PMID- 11504560
TI  - Bone morphogenetic protein-2 (BMP-2) and transforming growth factor-beta1 (TGF
      beta1) alter connexin 43 phosphorylation in MC3T3-E1 Cells.
AB  - BACKGROUND: Bone morphogenetic proteins (BMPs) and transforming growth factor
      betas (TGF-betas) are important regulators of bone repair and regeneration. BMP-2
      and TGF-beta1 have been shown to inhibit gap junctional intercellular
      communication (GJIC) in MC3T3-E1 cells. Connexin 43 (Cx43) has been shown to
      mediate GJIC in osteoblasts and it is the predominant gap junctional protein
      expressed in these murine osteoblast-like cells. We examined the expression,
      phosphorylation, and subcellular localization of Cx43 after treatment with BMP-2
      or TGF-beta1 to investigate a possible mechanism for the inhibition of GJIC.
      RESULTS: Northern blot analysis revealed no detectable change in the expression
      of Cx43 mRNA. Western blot analysis demonstrated no significant change in the
      expression of total Cx43 protein. However, significantly higher ratios of
      unphosphorylated vs. phosphorylated forms of Cx43 were detected after BMP-2 or
      TGF-beta1 treatment. Immunofluorescence and cell protein fractionation revealed
      no detectable change in the localization of Cx43 between the cytosol and plasma
      membrane. CONCLUSIONS: BMP-2 and TGF-beta1 do not alter expression of Cx43 at the
      mRNA or protein level. BMP-2 and TGF-beta1 may inhibit GJIC by decreasing the
      phosphorylated form of Cx43 in MC3T3-E1 cells.

PMID- 11504561
TI  - Flow cytometric assessment of the reactivity of a panel of monoclonal antibodies
      (mAb) against two populations of human dendritic cells (DC).
AB  - BACKGROUND: The identification of antigens on human DC has been a very difficult
      and elusive task because of the lack of appropriate reagents. Therefore, we
      evaluated by flow cytometry a panel of mAb that recognize antigens on human DC,
      aiming to determine the kinetics of DC antigen expression at 7, 14, 21 and 28
      days in (i) Dermal DC like cells (Mo-DC) and (ii) Langerhans cell like DC (Mo
      LC). In addition we aimed to identify markers for DC subpopulations. RESULTS: It
      was found at day 7, that mAb BG6, HP-F1, BU10, RFD-1, CMRF-44 recognized <20% of
      Mo-DC. In contrast, 7H5, ZM3.8, CDlb/c, 55K-2, MMR1.16, MMR190.BB3 and L25
      reacted with >50% of Mo-DC. Moreover, 7H5, ZM3.8, CMRF-56, CDlb/c, 55K-2,
      MMR1.16, MMR190.BB3 and L25 showed increased MFI reactivity against Mo-DC. mAb
      BG6, BU10 and CMRF-44 recognized <20% Mo-LC while RFD-1 reacted with 21% of Mo
      LC. In contrast, HP-F1 showed 87% of Mo-LC positive. Also, 7H5, ZM3.8, RFD-7,
      MR15-2, CDlb/c, 55K-2, MMR1.16, MMR190.BB3 and L25 reacted with >50% of Mo-LC.
      The increase in % of positive cells was paralleled by MFI increases. At day 14,
      fourteen mAb recognized >50% of the Mo-DC, while five recognized 20-50% of Mo-DC.
      BG6 reacted with 7% of the Mo-DC. Nineteen mAb recognized >48% of Mo-LC while BG6
      had negative reactivity. At day 21 and 28, all mAb reacted with >20% of Mo-DC and
      yielded a significant MFI with Mo-DC. Also nineteen mAb yielded significant MFI
      with Mo-LC while RFD-7 did not. CONCLUSIONS: The immunophenotyping assays
      demonstrated differences between the two DC populations as well as variations in
      the reactivity of the mAb at diverse time points, suggesting the existence of
      subpopulations within the Mo-DC and Mo-LC.

PMID- 11504562
TI  - Evidence that the RNAseH activity of the duck hepatitis B virus is unable to act
      on exogenous substrates.
AB  - BACKGROUND: The hepadnaviral reverse transcriptase can synthesize DNA on its
      native RNA template within viral cores but it is usually unable to synthesize DNA
      employing exogenous nucleic acids as a template. The mechanism of this template
      commitment is unknown. Here we provide evidence that the RNAseH activity of duck
      hepatitis B virus reverse transcriptase may also be unable to act on exogenous
      substrates. RESULTS: RNAseH assays were performed under a wide variety of
      conditions employing substrate RNAs of Duck Hepatitis B Virus sequence annealed
      to complementary DNA oligonucleotides and permeabilized intracellular viral core
      particles. Temperature, pH, cation type, salt concentration, substrate
      concentration, and the sequences of the cleavage sites were varied, and the
      effects of ATP and dNTPs on RNAseH activity were examined. duck hepatitis B virus
      RNAseH activity was not detected under any of these conditions, although E. coli
      or Avian Myeloblastosis Virus RNAseH activity could be detected under all
      conditions. Access of the RNA substrate to the enzyme within the viral cores was
      confirmed. CONCLUSIONS: These results imply that the RNAseH activity of the DHBV
      reverse transcriptase may not be able to degrade exogenous RNA:DNA
      heteroduplexes, although it can degrade heteroduplexes of the same sequence
      generated during reverse transcription of the endogenous RNA template. Therefore,
      the RNAseH activity appears to be "substrate committed" in a manner similar to
      the template commitment observed for the DNA polymerase activity.

PMID- 11504563
TI  - Asymmetric interactions in the adenosine-binding pockets of the MS2 coat protein
      dimer.
AB  - BACKGROUND: The X-ray structure of the MS2 coat protein-operator RNA complex
      reveals the existence of quasi-synmetric interactions of adenosines -4 and -10 in
      pockets formed on different subunits of the coat protein dimer. Both pockets
      utilize the same five amino acid residues, namely Val29, Thr45, Ser47, Thr59, and
      Lys61. We call these sites the adenosine-binding pockets. RESULTS: We present
      here a heterodimer complementation analysis of the contributions of individual A
      pocket amino acids to the binding of A-4 and A-10 in different halves of the
      dimer. Various substitutions of A-pocket residues were introduced into one half
      of single-chain coat protein heterodimers where they were tested for their
      abilities to complement Y85H or T91I substitutions (defects in the A-4 and A-10
      half-sites, respectively) present in the other dimer half. CONCLUSIONS: These
      experiments provide functional tests of interactions predicted from structural
      analyses, demonstrating the importance of certain amino acid-nucleotide contacts
      observed in the crystal structure, and showing that others make little or no
      contribution to the stability of the complex. In summary, Val29 and Lys61 form
      important stabilizing interactions with both A-4 and A-10. Meanwhile, Ser47 and
      Thr59 interact primarily with A-10. The important interactions with Thr45 are
      restricted to A-4.

PMID- 11504564
TI  - Differences in time of virus appearance in the blood and virus-specific immune
      responses in intravenous and intrarectal primary SIVmac251 infection of rhesus
      macaques; a pilot study.
AB  - BACKGROUND: HIV-I can be transmitted by intravenous inoculation of contaminated
      blood or blood product or sexually through mucosal surfaces. Here we performed a
      pilot study in the SIVmac251 macaque model to address whether the route of viral
      entry influences the kinetics of the appearance and the size of virus-specific
      immune in different tissue compartments. METHODS: For this purpose, of 2
      genetically defined Mamu-A*01-positive macaques, 1 was exposed intravenously and
      the other intrarectally to the same SIVmac251 viral stock and virus-specific CD8+
      T-cells were measured within the first 12 days of infection in the blood and at
      day 12 in several tissues following euthanasia. RESULTS: Virus-specific CD8+ T
      cell responses to Gag, Env, and particularly Tat appeared earlier in the blood of
      the animal exposed by the mucosal route than in the animal exposed intravenously.
      The magnitude of these virus-specific responses was consistently higher in the
      systemic tissues and GALT of the macaque exposed by the intravenous route,
      suggesting a higher viral burden in the tissues as reflected by the faster
      appearance of virus in plasma. Differences in the ability of the virus-specific
      CD8+ T-cells to respond in vitro to specific peptide stimulation were also
      observed and the greatest proliferative ability was found in the GALT of the
      animal infected by the intrarectal route. CONCLUSIONS: These data may suggest
      that the natural mucosal barrier may delay viral spreading. The consequences of
      this observation, if confirmed in studies with a larger number of animals, may
      have implications in vaccine development.

PMID- 11504565
TI  - Traumatic brain injury as a risk factor for Alzheimer disease. Comparison of two
      retrospective autopsy cohorts with evaluation of ApoE genotype.
AB  - BACKGROUND AND PURPOSE: The impact of traumatic brain injury (TBI) on the
      pathogenesis of Alzheimer disease (AD) is still controversial. The aim of our
      retrospective autopsy study was to assess the impact of TBE and ApoE allele
      frequency on the development of AD. MATERIAL AND METHODS: We examined 1. the
      incidence of AD pathology (Braak stageing, CERAD, NIA-Reagan Institute criteria)
      in 58 consecutive patients (mean age +/- SD 77.0 +/- 6.8 years) with residual
      closed TBI lesions, and 2. the frequency of TBI residuals in 57 age-matched
      autopsy proven AD cases. In both series, ApoE was evaluated from archival
      paraffin-embedded brain material. RESULTS: 1. TBE series: 12.1 % showed definite
      and 10.3% probable AD (mean age 77.6 and 75.2 years), only 2/13 with
      ApoEepsilon3/4. From 45 (77.6%) non-AD cases (mean age 78.2 years), 3 had
      ApoEepsilon3/4. The prevalence of 22.4% AD in this small autopsy cohort was
      significantly higher than 3.3% in a recent large clinical series and 14% in the
      general population over age 70. 2. In the AD cohort with ApoEepsilon4 allele
      frequency of 30% similar to other AD series, residuals of closed TBI were seen in
      4 brains (7%) (mean age +/- SD 78.2 +/- 6.4), all lacking the ApoEepsilon4
      allele. TBI incidence was slightly lower than 8.5% in the clinical MIRAGE study.
      CONCLUSIONS: The results of this first retrospective autopsy study of TBI,
      ApoEepsilon allele frequency, and AD confirm clinical studies suggesting severe
      TBI to be a risk factor for the development AD higher in subjects lacking
      ApoEepsilon4 alleles. Further studies in larger autopsy series are needed to
      elucidate the relationship between TBI, genetic predisposition, and AD.

PMID- 11504567
TI  - Evaluating Niger's experience in strengthening supervision, improving
      availability of child survival drugs through cost recovery, and initiating
      training for Integrated Management of Childhood Illness (IMCI).
AB  - BACKGROUND: WHO and UNICEF have recently developed the "Integrated Management of
      Childhood Illness" (IMCI) as an efficient strategy to assist developing countries
      reduce childhood mortality. Early experience with IMCI implementation suggests
      that clinical training is essential but not sufficient for the success of the
      strategy. Attention needs to be given to strengthening health systems, such as
      supervision and drug supply. RESULTS: This paper presents results of evaluating
      an innovative approach for implementing IMCI in Niger. It starts with
      strengthening district level supervision and improving the availability of child
      survival drugs through cost recovery well before the beginning of IMCI clinical
      training. The evaluation documented the effectiveness of the initial IMCI
      clinical training and referral. CONCLUSIONS: Strengthening supervision and
      assuring the availability of essential drugs need to precede the initiation of
      IMCI Clinical training. Longer term follow up is necessary to confirm the impact
      of the approach on IMCI preparation and implementation.

PMID- 11504566
TI  - The fission yeast COP9/signalosome is involved in cullin modification by
      ubiquitin-related Ned8p.
AB  - BACKGROUND: The function of the fission yeast cullins Pcu1p and Pcu4p requires
      modification by the ubiquitin-related peptide Ned8p. A recent report by Lyapina
      et al. shows that the COP9/signalosome (CSN), a multifunctional eight subunit
      complex, regulates Ned8p modification of Pcu1p. Disruption of caa1/csn1, which
      encodes subunit 1 of the putative S. pombe CSN, results in accumulation of Pcu1p
      exclusively in the modified form. However, it remained unclear whether this
      reflects global control of all cullins by the entire CSN complex. RESULTS: We
      demonstrate that multiple CSN subunits control Ned8p modification of Pcu3p,
      another fission yeast cullin, which, in complex with the RING domain protein
      Pip1p, forms a ubiquitin ligase that functions in cellular stress response. Pcu3p
      is modified by Ned8p on Lys 729 and accumulates exclusively in the neddylated
      form in cells lacking the CSN subunits 1, 3, 4, and 5. These CSN subunits co
      elute with Pcu3p in gel filtration fractions corresponding to approximately 550
      kDa and specifically bind both native and Ned8p-modified Pcu3p in vivo. While CSN
      does not influence the subcellular localization of Pcu3p, Pcu3p-associated in
      vitro ubiquitin ligase activity is stimulated in the absence of CSN. CONCLUSIONS:
      Taken together, our data suggest that CSN is a global regulator of Ned8p
      modification of multiple cullins and potentially other proteins involved in
      cellular regulation.

PMID- 11504568
TI  - Will the real heart-healthy diet please stand up!

PMID- 11504570
TI  - Bivalirudin for percutaneous coronary intervention and in acute coronary
      syndromes.
AB  - This review focuses on the use of bivalirudin as a replacement anticoagulant for
      heparin in patients undergoing percutaneous coronary intervention, or who are
      being treated for unstable angina pectoris, ST-elevation, or non-ST-elevation
      myocardial infarction. Potential advantages of bivalirudin include a lack of
      dependence on antithrombin III for anticoagulant activity, the ability to
      inactivate both fibrin-bound and soluble thrombin, a lack of aggregatory effects
      on platelets, a predictable anticoagulant response without monitoring, and a
      wider therapeutic window. Clinical trial results to date suggest that bivlirudin
      is at least as effective as heparin with superior safety due to lower bleeding
      rates.

PMID- 11504571
TI  - Platelet glycoprotein IIb/IIIa inhibitors for acute coronary syndromes: initiate
      treatment early or wait for the catheterization laboratory?
AB  - Treatment of patients with acute coronary syndromes (ACS) incorporates several
      approaches to reverse or mitigate the thrombus, which invariably is at the center
      of the pathophysiologic process of ACS. Pharmacologic and mechanical strategies
      are designed to prevent death, reduce myocardial necrosis, and stabilize the
      plaque to prevent later sequelae. Conventional antithrombotic therapy includes
      antiplatelet and anticoagulant drugs. Medications that inhibit the platelet
      glycoprotein IIb/IIIa receptor have been shown to be especially efficacious in
      the treatment of ACS. Recent clinical trials have validated a strategy of
      aggressive revascularization, particularly catheter-based percutaneous
      procedures. This review summarizes new trial results and provides a working
      algorithm for care of the patient with ACS.

PMID- 11504572
TI  - Anticoagulation for acute coronary syndromes and percutaneous coronary
      intervention in patients with heparin-induced thrombocytopenia.
AB  - Heparin-induced thrombocytopenia (HIT) is not uncommon in clinical practice, and
      may go unrecognized in a substantial number of patients. The pathophysiology of
      HIT has only recently been better understood. Patients with HIT may require
      anticoagulation for thrombotic complications that result in severe morbidity and
      mortality. These patients may also require anticoagulation for acute coronary
      syndromes (ACS), or during percutaneous coronary interventions (PCIs). The direct
      thrombin inhibitors are currently the anticoagulant of choice in HIT patients
      with ACS or those undergoing PCI, based on data from several large clinical
      trials in ACS and PCI populations, and data from smaller experiences,
      specifically in patients with HIT.

PMID- 11504573
TI  - Complications of oral antiplatelet medications.
AB  - One by-product of the flurry of large-scale clinical trials accompanying the
      emergence of drugs that inhibit platelet function is volumes of information
      chronicling the adverse effects of this class of medications. One aspect all
      antiplatelet drugs share is a propensity toward bleeding. Beyond that similarity,
      however, the different pharmacologic agents in this broad collection have few
      attributes in common. Aspirin, by virtue of its long history, has been studied
      most extensively, and has proven to be an exceptionally valuable therapy.
      However, the complicated adverse profile of this seemingly simple drug is
      commonly overlooked by practitioners and deserves clinical review. The
      thienopyridine class (including ticlopidine and clopidogrel) share certain
      peculiarities that continue to be clarified, including life-threatening
      thrombotic thrombocytopenia purpura. Dipyridamole is a veteran drug that is
      enjoying renewed attention as a prophylactic aid in preventing cerebrovascular
      events. One class, the oral platelet glycoprotein IIb/IIIa receptor inhibitors,
      has failed to find its way into clinical implementation due to an unfavorable
      balance between efficacy and adverse effect. This review summarizes the adverse
      profiles of each of these drug classes and draws on data gathered in large
      clinical studies.

PMID- 11504575
TI  - The role of lipoprotein(a) in the pathogenesis of atherosclerotic cardiovascular
      disease and its utility as predictor of coronary heart disease events.
AB  - Lipoprotein(a), is a highly heterogeneous lipoprotein, due to variations in the
      size of apolipoprotein(a), and the density of the apoB100-containing particles to
      which apo(a) is linked. Although high plasma levels of Lp(a) have been associated
      with an increased risk for atherosclerotic cardiovascular disease, the mechanism
      underlying this association is still largely undetermined, as is the potential
      role played by the particle's heterogeneity. Lp(a) pathogenicity may also be
      influenced by the action of environmental factors and post-translational events
      relating to oxidative processes, and the action of lipolytic and proteolytic
      enzymes. Complicating the study of Lp(a) are the competing methods for its
      quantification due to its complex structure, and the lack of standardized
      methodologies. The recognition that Lp(a) particles may not all be alike in
      atherogenic potential should encourage studies to identify genetic and nongenetic
      factors underlying its heterogeneity, in order to reach a better understanding of
      its actual impact on atherosclerotic cardiovascular disease.

PMID- 11504576
TI  - The optimal dietary strategy to manage risk associated with various
      dyslipidemias.
AB  - A successful dietary strategy should reduce coronary heart disease (CHD)
      endpoints, improve correctable risk factors for CHD, and provide for an overall
      healthful lifestyle. The therapeutic diet achieves a lowering of low-density
      lipoprotein cholesterol by limiting saturated fat and dietary cholesterol,
      avoiding an increase in trans fatty acids, and incorporates the use of dietary
      adjuncts such as an increase in dietary viscous fiber and dietary plant
      stanol/sterol esters. For those with elevated triglycerides and low high-density
      lipoprotein cholesterol, impaired fasting glucose, increased waist circumference
      and other stigmata of the metabolic syndrome, individualized and supervised
      weight loss, and regular physical activity is strongly recommended.

PMID- 11504577
TI  - Treatment of dyslipidemia in pre- and postmenopausal women with and without known
      atherosclerotic cardiovascular disease.
AB  - Cardiovascular disease is the primary cause of death among women in the United
      States, in part due to a very high prevalence of dyslipidemia. Clinical trials
      have shown that low-density lipoprotein cholesterol-lowering therapy can decrease
      angiographic progression of coronary disease and decrease clinical events among
      women and men. Although hormone replacement therapy has beneficial effects on the
      lipoprotein profile, its role in cardiovascular disease prevention remains
      unclear. The recently released Third Report of the National Cholesterol Education
      Program Expert Panel provides detailed guidelines for the management of
      dyslipidemia in women, with a focus on low-density lipoprotein cholesterol and
      intensity guided by risk of cardiovascular events.

PMID- 11504578
TI  - Potential use of Ca++ scanning to determine the need for and intensity of lipid
      lowering therapy in asymptomatic adults.
AB  - Deficiencies in traditional cardiovascular risk-factor assessment in asymptomatic
      individuals have led to the use of electron beam computed tomography (CT)
      scanning as a screening test for coronary artery disease. This novel approach is
      based on a secure pathologic foundation: the risk of coronary disease events is
      proportional to the severity and extent of underlying coronary atherosclerosis,
      and in middle-aged and elderly adults, calcified plaque is closely related to
      total plaque. Electron beam CT measures coronary calcium quickly, easily,
      accurately, and with a high degree of reproducibility. Coronary calcium is three
      to nine times higher in persons with fatal or nonfatal myocardial infarction than
      in age-matched controls, and four observational outcomes studies have
      demonstrated that the electron beam CT-derived coronary calcium score predicts
      fatal and nonfatal myocardial infarction. In symptomatic persons undergoing
      cardiac catheterization, electron beam CT is more closely associated with the
      severity of coronary atherosclerosis than are standard coronary risk factors.
      Preliminary evidence in asymptomatic persons indicates that the coronary calcium
      score also predicts coronary disease events more accurately than standard risk
      factors.

PMID- 11504579
TI  - Pathophysiology and treatment of the dyslipidemia of insulin resistance.
AB  - Insulin resistance, and the compensatory hyperinsulinemia that results, has been
      linked to a host of defects including glucose intolerance, diabetes,
      hypertension, dyslipidemia, endothelial dysfunction, impaired fibrinolysis, and
      subclinical inflammation. Patients with this metabolic syndrome have a markedly
      increased risk for the development of atherothrombotic cardiovascular disease.
      The characteristic dyslipidemia of insulin resistance consists of elevated
      triglyceride and triglyceride-rich lipoprotein levels, low levels of high-density
      lipoprotein cholesterol, and increased concentrations of small, dense low-density
      lipoprotein cholesterol. Management of this dyslipidemia typically involves a
      dual approach. Lifestyle modification is an essential component of any successful
      treatment plan, but alone is usually insufficient to correct these lipoprotein
      abnormalities. Medications that diminish insulin resistance and directly alter
      lipoproteins are also necessary in the majority of cases. Combinations of
      therapeutic agents are often required to optimize attainment of treatment goals.

PMID- 11504580
TI  - Targeting triglycerides as prognostic indicators and determining lowest values
      for patient benefit.
AB  - A number of reports demonstrate the importance of serum triglyceride values in
      predicting the clinical onset of vascular disease. However, adjustment for
      measurements highly correlated with triglyceride (TG) levels, such as history of
      diabetes, body mass index, and high-density lipoprotein cholesterol (HDL-C),
      lessen if not remove the TG contribution to outcomes. More recently, improved
      analytic approaches have more persuasively implicated triglycerides as
      independently relevant to the onset of cardiovascular disease. Elevated TG values
      are the consequence of larger TG-rich particles, including very low density
      lipoprotein and atherogenic intermediate particles, which are in turn associated
      with dense low-density lipoprotein. It has been observed that a reduction in TG
      concentrations often proceeds in parallel with improved clinical outcomes;
      however, direct correlation between the two has been elusive. This has been
      demonstrated in multiple pharmacologic trials. However, an improvement in these
      relationships has been observed when TG-correlated measurements of intermediate
      particles, low-density lipoprotein density, and HDL-C have been made. National
      guidelines for cholesterol treatment have now incorporated a TG greater than 200
      mg/dL as a secondary treatment trigger, which targets apolipoprotein B-related
      particles, represented by non-HDL-C (total cholesterol minus HDL-C), as the
      suggested goal of therapy.

PMID- 11504581
TI  - Kratschmer and nasal reflexes.

PMID- 11504582
TI  - On reflexes from the nasal mucous membrane on respiration and circulation.

PMID- 11504583
TI  - Stretch induces a growth factor in alveolar cells via protein kinase.
AB  - Positive-pressure mechanical ventilation can injure the lung, causing edema and
      alveolar inflammation in a complication termed ventilator-induced lung injury
      (VILI). Cytokines such as interleukin-8 (IL-8) reportedly are important in this
      inflammatory response. On the other hand, hepatocyte growth factor (HGF) promotes
      regeneration of the lung, and delays pulmonary fibrosis. We postulated that
      cyclic stretch upregulates production and release of both of mediators. Human
      alveolar epithelial cells (A549) cultured on a silicoelastic membrane were tested
      for mRNA expression and release of IL-8 and HGF after cyclic stretch in vitro.
      Stretch induced mRNA expression and release of these mediators. The signaling
      pathway from cyclic stretch to release of IL-8 and HGF appeared to involve
      protein kinase C in the signal transduction pathway.

PMID- 11504584
TI  - Sensitivity of vagal afferent endings to chemical irritants in the rat lung.
AB  - This study was carried out to investigate the relationship between the conduction
      velocity of the vagal afferents arising from the rat lungs and their
      sensitivities to capsaicin, other chemical irritants, and lung inflation. We
      recorded single-unit activities of vagal pulmonary afferents (n = 205) in
      anesthetized, open-chest rats, and distinguished C fibers (conduction velocity <
      2 m/sec) from myelinated afferents; the latter group was further classified into
      rapidly adapting pulmonary receptors (RARs) and slowly adapting pulmonary stretch
      receptors (SARs) on the basis of their adaptation indexes to lung inflation.
      Right-atrial injection of capsaicin (1 microg/kg) evoked an abrupt and intense
      stimulatory effect in 88.9% (64/72) of the pulmonary C fibers tested, but only a
      mild stimulation in 6.3% (3/48) of the RARs and none of the SARs. Other inhaled
      and injected chemical stimulants (e.g., cigarette smoke, lactic acid) activated
      68.9% (42/61) of the pulmonary C fibers. The same chemical irritants exerted a
      mild stimulatory effect in only 14.5% (8/55) of the RARs; this subgroup of RARs
      exhibited a low or no baseline activity, and half of them were located near the
      hilum. Chemical stimulants had little or no effect on SARs. The response of
      pulmonary C fibers to lung inflation (tracheal pressure = 30 cm H2O) was not only
      extremely weak, but also showed a longer onset latency and an irregular pattern.
      In a sharp contrast, lung inflation evoked rapid and vigorous discharges in both
      RARs and SARs. In conclusion, C fibers are the primary type of chemosensitive
      vagal pulmonary afferents in rat lungs.

PMID- 11504585
TI  - High strength stimulation of the vagus nerve in awake humans: a lack of
      cardiorespiratory effects.
AB  - Vagus nerve stimulation is used to reduce the frequency and intensity of seizures
      in patients with epilepsy. In the present study four such patients were studied
      while awake. We analyzed the physiological responses to vagus nerve stimulation
      over a broad range of tolerable stimulus parameters to identify vagal A-fiber
      threshold and to induce respiratory responses typical of C-fiber activation. A
      fiber threshold was determined by increasing stimulation current until laryngeal
      motor A-fibers were excited (frequency=30 Hz). With A-fiber threshold
      established, C-fiber excitation was attempted with physiologically appropriate
      stimulus parameters (low frequency and high amplitude). RESULTS: A-fiber
      thresholds were established in all patients, threshold currents ranged between
      0.5 and 1.5 mA. Stimulation at lower frequency (2-10 Hz) and higher amplitudes
      (2.75-3.75 mA) did not produce cardiorespiratory effects consistent with C-fiber
      activation. It is possible that such effects were not observed because vagal C
      fibers were not excited, because C-fiber effects were masked by the 'wakeful
      drive' to breathe, or because epilepsy or the associated therapy had altered
      central processing of the vagal afferent inputs.

PMID- 11504586
TI  - Development of in vivo ventilatory and single chemosensitive neuron responses to
      hypercapnia in rats.
AB  - We used pressure plethysmography to study breathing patterns of neonatal and
      adult rats acutely exposed to elevated levels of CO2. Ventilation (VE) increased
      progressively with increasing inspired CO2. The rise in VE was associated with an
      increase in tidal volume, but not respiratory rate. In all animals studied, the
      CO2 sensitivity (determined from the slope of the VE vs. inspired % CO2 curve)
      was variable on a day to day basis. Chemosensitivity was high in neonates 1 day
      after birth (P1) and fell throughout the first week to a minimum at about P8.
      Chemosensitivity rose again to somewhat higher values in P10 through adult rats.
      The developmental pattern of these in vivo ventilatory responses was different
      than individual locus coeruleus (LC) neuron responses to increased CO2. The
      membrane potential (V(m)) of LC neurons was measured using perforated patch
      (amphotericin B) techniques in brain slices. At all ages studied, LC neurons
      increased their firing rate by approximately 44% in response to hypercapnic
      acidosis (10% CO2, pH 7.0). Thus the in vivo ventilatory response to hypercapnia
      was not correlated with the V(m) response of individual LC neurons to hypercapnic
      acidosis in neonatal rats. These data suggest that CO2 sensitivity of ventilation
      in rats may exist in two forms, a high-sensitivity neonatal (or fetal) form and a
      lower-sensitivity adult form, with a critical window of very low sensitivity
      during the period of transition between the two (approximately P8).

PMID- 11504587
TI  - Modulation of breathing by mu1 and mu2 opioid receptor stimulation in neonatal
      and adult rats.
AB  - Opioid modulation of breathing during postnatal development through to the adult
      was investigated in the rat. Respiratory frequency, tidal volume and minute
      volume were recorded in unanesthetized, unrestrained rat pups and adults using
      barometric plethysmography. Subjects were administered the highly selective mu
      opioid agonists dermorphin and fentanyl. Fentanyl, which readily crosses the
      blood-brain barrier, was included to ensure that developmental changes in blood
      brain barrier restrictions did not mask some of the dermorphin effects in older
      neonates. Drugs were administered subcutaneously in neonates and adults, although
      dermorphin was given by intracerebroventricular route only in adults. In
      neonates, mu agonist administration caused a gasping-like pattern of breathing,
      characterized by a marked fall in frequency and a smaller increase in tidal
      volume. The gasping response was prevented by pre-treatment with the long-acting
      mu1 antagonist naloxonazine (NALZ). In the presence of NALZ, mu agonists elicited
      only a small, but significant, reduction in tidal volume. Both dermorphin and
      fentanyl showed more potent activity in younger pups than in older pups, possibly
      in the case of dermorphin because of developmental maturation of blood-brain
      barrier function. In adults, fentanyl and dermorphin both caused a reduction in
      frequency and minute volume. The response of adults to fentanyl, but not
      dermorphin, was prevented by NALZ. These results suggest that both mu1 and mu2
      receptors contribute to opioid-induced respiratory depression during neonatal and
      adult life.

PMID- 11504588
TI  - The morphology of periodic breathing in infants and adults.
AB  - To test the hypothesis that the crescendo-decrescendo type of pattern of periodic
      breathing is more common in infants than in adulthood, we examined the
      morphologies of periodic breathing in four groups of subjects: group 1 (n=10,
      gestational age 30+/-1 week), group 2 (n=10, GA 31+/-1 week), group 3 (n=10, GA
      38+/-1 week), and group 4 (n=10, age 50+/-4 years). Respiratory pattern and
      ventilation were measured using a flow-through system. The breathing morphologies
      were defined according to the respiratory flow. We found (1) a predominant
      crescendo-decrescendo pattern in preterm infants (groups 1 and 2, >50%) and this
      changed to a predominant decrescendo breathing in adults (group 4, 50%); (2)
      total breathing cycle and its phases did not change significantly among the
      neonatal groups, but they almost doubled in adult subjects; however, the number
      of breaths per breathing interval remained the same (crescendo-decrescendo) or
      less (flat and decrescendo) in adults as compared to preterm infants; (3) the
      duty cycle (breathing interval/cycle duration) remained consistent with age; and
      (4) at the beginning of each breathing interval, alveolar P(CO2) was highest and
      alveolar P(O2) and O2 saturation lowest. The findings suggest a change in the
      strategy of the respiratory control system during periodic breathing between the
      infant and the adult, perhaps dictated by mechanical and chemoreceptor
      limitations early in age, with a switch from a crescendo-decrescendo to a
      predominantly decrescendo pattern.

PMID- 11504589
TI  - Effects of respiratory muscle training versus placebo on endurance exercise
      performance.
AB  - We evaluated the effects of a 5 week (25 sessions); (30-35 min/day, 5 days/week),
      respiratory muscle training (RMT) program in nine competitive male cyclists. The
      experimental design included inspiratory resistance strength training (3-5
      min/session) and hyperpnea endurance training (30 min/session), a placebo group
      which used a sham hypoxic trainer (n=8), and three exercise performance tests,
      including a highly reproducible 8 km time trial test. RMT intensity, measured
      once a week in terms of accumulated inspiratory pressure and the level of
      sustainable hyperpnea increased significantly after 5 weeks (+64% and +19%,
      respectively). The RMT group showed a significant 8% increase in maximal
      inspiratory pressure (P<0.05) while the placebo group showed only a 3.7% increase
      (P>0.10). RMT and placebo groups both showed significant increases in the fixed
      work-rate endurance test performance time (+26% and +16%, respectively) and in
      the peak work-rate achieved during the incremental maximal oxygen consumption
      (V(O2)max) test (+9 and +6%). The 8 km time trial performance increased 1.8+/
      1.2% (or 15+/-10 sec; P<0.01) in the RMT group with 8 of 9 subjects increasing;
      the placebo group showed a variable non-significant change in 5 of 8 subjects (
      0.3+/-2.7%, P=0.07). The changes observed in these three performance tests were
      not, however, significantly different between the RMT and placebo groups. Heart
      rate, ventilation, or venous blood lactate, at equal work-rates during the
      incremental exercise test or at equal times during the fixed work-rate endurance
      test were not changed significantly across these exercise trials in either group.
      We propose that the effect of RMT on exercise performance in highly trained
      cyclists does not exceed that in a placebo group. Significant placebo and test
      familiarization effects must be accounted for in experimental designs utilizing
      performance tests which are critically dependent on volitional effort.

PMID- 11504590
TI  - Effects of deep inspiration on bronchoconstriction in the rat.
AB  - It is important to understand the mechanisms by which a deep inspiration (DI)
      affects bronchoconstriction in rodents so that their relevance as animal models
      of asthma can be assessed. We investigated the effect of DI on respiratory input
      impedance after methacholine inhalation in four groups of rats: a control group,
      a group receiving DI prior to challenge, and two groups receiving different
      degrees of DI after challenge. We measured respiratory input impedance for 15 min
      following a challenge. This provided time-courses approximating the resistance of
      the conducting airways and the impedance of the respiratory tissues. We found no
      significant difference in the peak changes in airway resistance comparing the
      control group and any of the DI groups following challenge. However, the peak
      increase in tissue impedance was reduced in the group receiving the largest DI
      after challenge. Our results thus suggest that the DIs that we administered were
      neither bronchodilatory nor bronchoprotective, but that they were able to reduce
      the amount of airway closure occurring following bronchoconstriction.

PMID- 11504591
TI  - Sublingual electrical stimulation of the tongue during wakefulness and sleep.
AB  - Pharyngeal obstruction in patients with obstructive sleep apnea (OSA) is thought
      to result from decreased upper airway muscle tone during sleep. The goal of the
      present study was to estimate the role of the tongue muscles in maintaining
      pharyngeal patency during sleep. Using non-invasive, sub-lingual surface
      electrical stimulation (ES), we measured tongue protrusion force during
      wakefulness and upper airway resistance during sleep in seven healthy subjects
      and six patients with OSA. During wakefulness, ES produced similar protrusion
      forces in healthy subjects and patients with OSA. ES of the anterior sublingual
      surface, causing preferential contraction of the genioglossus, resulted in
      smaller effects than combined ES of the anterior and lateral surface, which also
      stimulated tongue retractors. During sleep, trans-pharyngeal resistance decreased
      and peak inspiratory flow rate increased from 319+/-24 to 459+/-27 and from 58+/
      16 to 270+/-35 ml/sec for healthy subjects and OSA patients, respectively
      (P<0.001). However, ES was usually unsuccessful in reopening the upper airway in
      the presence of complete apneas. We conclude that non-invasive ES of the tongue
      improves flow dynamics during sleep. Combined activation of tongue protrusors and
      retractors may have a beneficial mechanical effect. The magnitude of responses
      observed suggests that in addition to the stimulated muscles, other muscles
      and/or forces have a substantial impact on pharyngeal patency.

PMID- 11504592
TI  - Genioglossal length and EMG responses to static upper airway pressures during
      hypercapnia in goats.
AB  - Mechanoreflexes that activate genioglossus electromyogram (EMGgg) in response to
      negative upper airway pressure (UAP) may help defend airway patency in
      obstructive sleep apnea. Hypercapnia may affect mechanoreflexes by increasing
      EMGgg response to actively reduce genioglossus length (Lgg, measured by
      sonomicrometry). We hypothesized that during normocapnia, Lgg would be reduced at
      positive, and increased at negative UAP but hypercapnia would increase EMGgg
      responses to negative pressures and cause Lgg reductions. At 0, 3.5 and 7%
      inhaled CO2 (balance O2), Lgg and EMGgg were measured during static negative and
      positive UAP applied to the isolated upper airway in four unanesthetized goats.
      At 3.5 and 7% CO2 EMGgg was significantly increased and Lgg decreased with
      negative pressure while EMGgg was also greater at 7 than 0% CO2 (P<0.05). Non
      significant pressure related Lgg changes were observed during normocapnia. These
      results suggest that hypercapnia may stimulate greater mechanoreflex EMGgg
      activation and consequent Lgg reduction in response to negative UAP application.

PMID- 11504593
TI  - Characterising respiratory airway gas mixing using a lumped parameter model of
      the pulmonary acinus.
AB  - A lumped parameter model of a human pulmonary acinus is derived using results
      from gas mixing simulations in an anatomically-based asymmetric multi-branching
      model of the acinus coupled to a symmetric conducting airway model. The model
      respiratory airways change length in proportion to the cube root of their volume
      change, and the diameters are updated accordingly assuming constant duct cross
      sectional area. The lumped parameter model applies a flux boundary condition at
      the end of a transitional bronchiole during inspiration to enable realistic
      concentration changes at this position; during expiration inspiratory parameters
      are used to predict concentrations at the end of the associated transitional
      bronchiole. The predicted concentrations are used as time-varying fixed boundary
      conditions at the end of the transitional bronchiole in conducting airway models
      during expiration. The current lumped parameter model is most accurate for tidal
      volumes between 500 and 1500 ml, and equal inspiration and expiration durations
      of 2 sec. The model's accuracy decreases for changes in breath duration.

PMID- 11504594
TI  - Multibreath washout analysis: modelling the influence of conducting airway
      asymmetry.
AB  - The contributions of respiratory and conducting airway asymmetry, gas exchange,
      and non-uniform ventilation to the sloping alveolar plateau in phase III of the
      gas washout curve are investigated using mathematical models of the human lung.
      The models range from fully symmetric, to a detailed asymmetric conducting airway
      model coupled with 29445 lumped parameter respiratory airway models. A gas
      transport equation is solved in the models using a Lagrange-Galerkin method. The
      alveolar slope is normalised by the mean expired gas concentration to give S(n).
      The model results confirm that first breath S(n) is influenced mainly by
      respiratory airway asymmetry, and that at near-normal levels of ventilation the
      conducting airway asymmetry contributes a significant amount to further increases
      in S(n). Gas exchange moderates the plot of S(n) against breath number, such that
      it approaches a plateau in later breaths. Non-uniform flow also alters S(n),
      indicating that an accurate description of the pleural pressure gradient will be
      necessary for more accurate simulations.

PMID- 11504595
TI  - Exercise alters serum pneumoprotein concentrations.
AB  - To determine the effect of exercise on serum levels of Clara cell protein (CC16)
      and surfactant-associated protein A (SP-A), serum was collected from 14 healthy
      subjects 1 h after maximal and sub-maximal exercise. Healthy volunteers
      participated on separate occasions in a control (no exercise) session, simulated
      firefighting tasks for 30 min (n=14), and intermittent treadmill exercise at near
      maximal heart rates for 60 min (n=10). Serum samples and induced sputum samples
      were collected 1 h post exercise. Induced sputum fluid was analyzed for tumor
      necrosis factor alpha (TNF-alpha), an inflammatory mediator produced by pulmonary
      macrophages. Serum CC16 levels increased significantly with both firefighting
      tasks (15+/-13 microg/L vs. 9+/-4 microg/L, P=0.047) and treadmill exercise (15+/
      8 microg/L vs. 9+/-4 microg/L, P<0.01). Serum SP-A concentrations did not change
      compared to control with either firefighting tasks (247+/-106 microg/L vs. 247+/
      96 microg/L, P=0.84) or treadmill exercise (251+/-89 microg/L vs. 285+/-87
      microg/L, P=0.44). TNF-alpha concentrations in sputum supernatant showed no
      significant difference from controls. These results show an increase in serum
      CC16 after exercise. This must be considered when utilizing serum CC16 to
      determine the presence of lung injury in settings that combine exercise and toxic
      exposures.

PMID- 11504596
TI  - Newer antiepileptic drugs: advantages and disadvantages.
AB  - The choice of an antiepileptic drug depends firstly on its efficacy in specific
      seizure types and epilepsies. However, it is imperative to consider whether
      possible adverse events will outweigh any benefits. The advantages and
      disadvantages of vigabatrin, lamotrigine, gabapentin, topiramate, tiagabine and
      felbamate are considered in some detail, and oxcarbazepine, stiripentol,
      remacemide, zonisamide and levetiracetam more briefly. Vigabatrin is effective
      for partial seizures and infantile spasms, but visual field defects are limiting
      its use. Lamotrigine has a wide spectrum, needs to be prescribed with care.
      Gabapentin is unlikely to cause adverse effects, but has relatively poor
      efficacy. Topiramate is widely effective, but can be poorly tolerated. Tiagabine
      is relatively untried in childhood epilepsies. The use of felbamate is restricted
      to severe refractory epilepsies. Stiripentol can be effective in severe myoclonic
      epilepsy in infancy. Zonisamide has a special place in the progressive myoclonus
      epilepsies. Levetiracetam, remacemide and oxcarbazepine have been used mainly for
      partial seizures: further studies of their roles in other circumstances are
      required.

PMID- 11504597
TI  - Galactonojirimycin derivatives restore mutant human beta-galactosidase activities
      expressed in fibroblasts from enzyme-deficient knockout mouse.
AB  - Ten low molecular compounds analogous to galactose were screened for inhibition
      of human beta-galactosidase activity. Among them, 1-deoxy-galactonojirimycin and
      N-(n-butyl)-deoxy-galactonojirimycin showed an inhibitory effect at high
      concentrations. However, they restored mutant enzyme activities expressed in
      enzyme-deficient knockout mouse fibroblasts and human beta-galactosidosis
      fibroblasts at lower intracellular concentrations. This effect was more
      remarkable on G(M1)-gangliosidosis mutations (R201C, I51T, R201H, R457Q) than
      Morquio B disease mutations (W273L, Y83H). These low molecular compounds pass
      though the blood-brain barrier in mice. We hope that this new therapeutic
      approach will become clinically applicable in the near future.

PMID- 11504598
TI  - Progressive neuronal loss in the ventral posterior lateral and medial nuclei of
      thalamus in Niemann-Pick disease type C mouse brain.
AB  - Niemann-Pick disease type C (NP-C) disease is a progressive and fatal
      neurological disorder characterized by accumulation of cholesterol and
      glycosphingolipids in peripheral tissues and that of glycosphingolipids in the
      brain. A C57BL/KsJ-npc1(spm) mutant strain is a genetically authentic model of NP
      C. This study investigated neuronal cell loss and lipid accumulation in the
      npc1(spm) mouse brain. Nissl-staining revealed abundant swollen neurons in the
      neocortex, piriform cortex, hippocampus and basal ganglia at 3-4 wk of age. In
      addition to loss of the Purkinje cells, we found a conspicuous cell loss in the
      ventral posterial lateral (VPL) and medial (VPM) nuclei of thalamus, which became
      apparent after 4-5 wk. Biochemical analyses revealed no increase of cholesterol
      in the lipid extracts whereas a substantial accumulation of cholesterol was
      detectable in most of the large neurons by filipin staining in the brain of
      homozygous mice. In contrast to the diffuse staining pattern in normal brains,
      the neuropils of the neurons in the brain of homozygous mice were stained in a
      punctate pattern. The ubiquitous accumulation excludes a direct role of
      cholesterol in the progressive neuronal loss in the Purkinje cell layer and in
      the VPL and VPM of the thalamus.

PMID- 11504599
TI  - The significance of type 1 fiber atrophy (hypotrophy) in childhood neuromuscular
      disorders.
AB  - To determine the incidence of selective type 1 fiber atrophy (hypotrophy) and its
      possible significance in various muscle diseases of childhood, we reviewed 2212
      muscle biopsies from children which we had examined in the past 20 years
      histochemically with ATPase staining. Type 1 fiber atrophy was seen in a variety
      of neuromuscular disorders, but predominantly in congenital myopathies, including
      all patients with congenital fiber type disproportion myopathy (20 patients),
      central core disease (12 patients) and multicore disease (four patients).
      Although type 1 fiber atrophy was not a constant feature in nemaline myopathy and
      myotubular myopathy, all patients with these diseases had abnormal fiber type
      distribution which included type 1 fiber predominance both with and without type
      2B fiber deficiency. Together with abnormal fiber type distribution, type 1 fiber
      atrophy was a common finding in childhood neuromuscular disorders, especially
      congenital myopathies.

PMID- 11504600
TI  - Long-term effect of flunarizine on patients with alternating hemiplegia of
      childhood in Japan.
AB  - To determine the effect of flunarizine therapy on patients with alternating
      hemiplegia of childhood (AHC), we sent a questionnaire by mail to council members
      of the Japanese Society of Child Neurology. We collected 28 AHC patients, and
      studied their clinical courses and the effects of drug therapy. All of the
      patients had received flunarizine. In 18 of the 28 patients, flunarizine reduced
      the severity, duration, or frequency of the hemiplegic attacks. No other drug was
      more effective than flunarizine. Some flunarizine non-effective patients were
      severely deteriorated, for example, they had dementia or were ventilator
      assisted. Flunarizine had not only a short-term effect, i.e. it reduced the
      hemiplegic attacks, but also a long-term effect on the motor and intellectual
      development in some patients with AHC. Flunarizine is still an essential drug for
      treating AHC.

PMID- 11504601
TI  - Clinical and EEG findings in 18 cases of late infantile neuronal ceroid
      lipofuscinosis.
AB  - The objective of this study was to present clinical and electroencephalographic
      findings in 18 cases with late infantile neuronal ceroid lipofuscinoses, focusing
      on features that assist early diagnosis. Clinical and EEG findings have been
      described in the past for classic types, but several variants have recently been
      reported. The authors reviewed the clinical and EEG findings of 18 childhood
      onset neuronal ceroid lipofuscinoses cases. In the late infantile neuronal ceroid
      lipofuscinoses type, both typical and variant cases have been observed. In this
      type, the presence of a particular pseudoperiodic EEG pattern that we found in
      15/18 patients and observed in the first stages of the disease could be useful in
      early diagnosis, especially if associated with the absence of sleep spindles. A
      precise nosological classification, based both on clinical and instrumental
      findings is the prerequisite for a correct genotype-phenotype correlation that
      could greatly improve our knowledge of this disease, providing a better
      understanding of pathogenesis and increasing our ability to treat it.

PMID- 11504602
TI  - A functional magnetic resonance imaging study during sentence reading in Japanese
      dyslexic children.
AB  - A functional magnetic resonance imaging (fMRI) study during Japanese 'kana'
      readings was performed on Japanese dyslexic children. Five dyslexic children
      (aged 9-12 years) and five healthy children (aged 9-11 years) were investigated.
      The fMRI examination was performed by getting these children to read sentences
      constructed from Japanese phonograms, 'kana', compared with staring at
      meaningless figures as a control task. All control subjects showed activation of
      the left middle temporal gyrus. In the dyslexic children, the activation of the
      middle temporal gyrus was rather vague. However, other distinctively activated
      regions were detected as follows: the bilateral occipital cortex in two
      dyslexics, the inferior part of the frontal regions in two other dyslexics, and
      both the bilateral occipital cortex and the inferior part of precentral gyrus in
      the remaining one. These results indicate compensatory management processes for
      the unskilled reading ability of dyslexic children. The present results were
      similar to previous ones for adult dyslexia with the Roman alphabet, and suggest
      that brain malfunction in dyslexia during the task of reading must be common
      despite differences in languages.

PMID- 11504603
TI  - Prevalence of positive anticardiolipin antibody in benign infantile convulsion.
AB  - We report six anticardiolipin antibody (aCL)-positive cases among 18 children
      with epilepsy showing various seizure types in our initial study. These six cases
      revealed normal coagulation tests. As three of these six cases involved benign
      infantile convulsion (BIC), we further investigated the high frequency of
      positive aCL-Immunoglobulin (Ig) G in BIC in our subsequent study of nine cases
      that included three cases from the previous study and an additional six BIC cases
      followed and/or diagnosed by co-author (T.K.). As a result, eight of nine BIC
      cases were positive for aCL-IgG and the values of aCL-IgG decreased over long
      term observation in three of these cases. The frequency of positivity for aCL-IgG
      in BIC was obviously higher than that of controls. Based on these results, we
      suggest that some immunological responses may be responsible for the pathogenesis
      of BIC.

PMID- 11504604
TI  - The gene copy ratios of SMN1/SMN2 in Japanese carriers with type I spinal
      muscular atrophy.
AB  - Spinal muscular atrophy is an autosomal recessive neurodegenerative disorder with
      progressive weakness and atrophy of voluntary muscles. The survival motor neuron
      gene (SMN) is present in two highly homologous copies (SMN1 and SMN2) on
      chromosome 5q13. Homozygous deletion of exons 7 and 8 of SMN1 is responsible for
      spinal muscular atrophy. In spinal muscular atrophy patients, SMN2 partially
      compensates for the lack of SMN1. Previously, we reported the relatively high
      incidence of a large deletion including the SMN1 region in Japanese spinal
      muscular atrophy type I patients. In order to further establish the genetic
      background of Japanese spinal muscular atrophy type I patients, we investigated
      the SMN1/SMN2 ratio in the carriers. In normal individuals, there is one copy of
      each gene on the chromosome (the SMN1/SMN2 ratio was 1). Among 15 carriers (14
      parents and one carrier sibling of Japanese type I spinal muscular atrophy
      patients with homozygous deletion of exons 7 and 8 of SMN1), we found that the
      SMN1/SMN2 ratio was 0.5 or 1 in 11 (73.3%) carriers. The remaining four carriers
      had an SMN1/SMN2 ratio of 1/3. This finding supports the idea that deletion
      rather than conversion is the main genetic event in type I spinal muscular
      atrophy. In addition, the ratio of SMN1/SMN2 among Japanese carriers, which was
      thought to be higher than that of the Western population, was compatible with the
      results obtained in Western populations. For further insight into the
      characteristic genetic background of spinal muscular atrophy in Japanese,
      determination of the gene copy number is essential.

PMID- 11504605
TI  - Motor functions in non-ambulatory children with spastic diplegia and
      periventricular leukomalacia.
AB  - The course of acquisition of various gross motor skills and changes in their
      patterns with advancing age, in addition to joint contracture, hand function, and
      mental ability, were investigated in 20 non-ambulatory children with spastic
      diplegia and periventricular leukomalacia. Among the diplegic children studied,
      those with lower locomotive ability also had lower hand function, lower mental
      ability and slower acquisition of gross motor skills. All subjects could roll by
      24 months of age. Fourteen patients could creep by 18 months of age, and the
      remaining six by 30 months. Crawling was observed in only five patients with mild
      locomotive disability as a final locomotive pattern on the floor. Among ten
      patients with mild locomotive disability, three could sit by 2 years of age, six
      by 3 years, and one by 4 years. Among ten patients with severe disability, two,
      two, four and two children could sit at the ages of 2, 3, 4 and 5 years,
      respectively. Twelve patients could walk with support at between 2 and 5 years of
      age. Delay in acquisition of creeping or sitting differed somewhat among subjects
      with similar final locomotive disability. The majority of subjects with severe
      locomotive disability developed contracture of the hips and knees. Only two
      patients with mild disability had contracture of the ankles.

PMID- 11504606
TI  - The variety of visual perceptual impairments in pre-school children with
      perinatal brain damage.
AB  - To study the selectivity of visual perceptual impairment in children with early
      brain injury, eight visual perceptual tasks (L94), were administered to
      congenitally disabled children both with and without risk for cerebral visual
      impairment (CVI). The battery comprised six object-recognition and two
      visuoconstructive tasks. Seven tasks were newly designed. For these normative
      data are presented (age 2.75-6.50 years). Because the recognition tasks required
      object naming, each item included a canonical control drawing and visual
      perceptual ability was evaluated relative to the non-verbal intelligence level,
      instead of chronological age. In 22 multiple disabled children with no
      indications of CVI, the frequency of impairment did not exceed that in the
      reference sample for any L94 task. In contrast, in 57 5-year-old children who
      were at risk for CVI due to pre-maturity or birth asphyxia, a significant
      increase in the frequency of impairment was seen on six L94 tasks (range 12-38%).
      However, only five children had more than two impairments, indicating that the
      deficits were selective, not pervasive. We conclude that early brain lesions
      interfere with the functioning of particular visual subsystems, yet leave other
      subsystems intact and functioning within the normal range.

PMID- 11504607
TI  - Prolonged suppression of brain nitric oxide synthase activity by 7-nitroindazole
      protects against cerebral hypoxic-ischemic injury in neonatal rat.
AB  - Nitric oxide mediates glutamate-induced excitotoxicity associated with cerebral
      hypoxia-ischemia through production in the brain by several isoforms of nitric
      oxide synthase (NOS). We examined the influence of the selective neuronal NOS
      inhibitor, 7-nitroindazole (7-NI), on brain NOS activity and its neuroprotective
      effects against cerebral hypoxic-ischemic injury in the postnatal day (PND) 7
      rat. In the first set of experiments, 7-NI (50 mg/kg) administered
      intraperitoneally (i.p.) transiently inhibited NOS activity to 40% below the
      vehicle control level at 1 h after injection (P<0.001, analysis of variance
      (ANOVA)). In contrast, 7-NI (100 mg/kg, i.p.) inhibited NOS activity to 56% below
      the control level at 1 h with prolonged suppression of NOS activity at 3, 6, 9
      and 12 h after injection. Two-factor ANOVA revealed an overall effect on NOS
      activity of 7-NI treatment (P<0.001) and time after injection (P<0.001). In the
      second set of experiments, 7-NI (50, 100 mg/kg) or an equal volume of vehicle was
      administered after unilateral carotid artery ligation, but 30 min before hypoxia
      in PND 7 rats. 7-NI (100 mg/kg) significantly protected against cerebral hypoxic
      ischemic injury (100 mg/kg of 7-NI, 1.7+/-1.0% damage; control, 8.7+/
      1.6%,P<0.05). 7-NI administered 15 min after cerebral hypoxia-ischemia was not
      neuroprotective. The data suggest that the protective effect of 7-NI is dose
      dependent, and is related to the duration of suppressed NOS activity.

PMID- 11504608
TI  - Encephalocraniocutaneous lipomatosis associated with iris coloboma,
      chorioretinitis and spinal cord involvement: a case report.
AB  - A 9-year-old boy with a history of lipoma excision and laminectomy at the Th10-11
      levels, resulting in incomplete paraparesis and neurogenic bladder, was admitted
      for a comprehensive rehabilitation programme. Physical examination revealed an
      ipsilateral focal dermal hypoplastic defect within an area of alopecia and a
      subcutaneous lipomatous tissue on the left temporo-parietal region of the scalp.
      Iris coloboma and chorioretinitis were diagnosed on the left eye. He also had
      mild mental retardation and triparesis. Magnetic resonance imaging of the brain
      and the spine demonstrated hyperintense masses which were consistent with lipoma.
      Although in the literature three cases of encephalocraniocutaneous lipomatosis
      (ECCL) concomitant with spinal cord involvement have been reported, to our
      knowledge iris coloboma and chorioretinitis in ECCL have not been reported
      previously. In conclusion, we would like to stress that aside from known
      ophthalmological malformations, iris coloboma and chorioretinitis may also be
      observed in ECCL and that all patients who have been diagnosed as having ECCL
      should be examined for spinal cord involvement.

PMID- 11504609
TI  - Early infantile epileptic encephalopathy (Ohtahara syndrome) after maternal
      electric injury during pregnancy: etiological considerations.
AB  - Early infantile epileptic encephalopathy (EIEE) is a polyetiologic age-dependent
      neurological disorder. We present two patients with EIEE whose mothers
      experienced electric injury during pregnancy. After the accident one mother
      noticed decreased fetal movements. Neither other prenatal factors nor intrapartal
      damage or postnatally examined structural, metabolic or infectious causes which
      might have been responsible for the EIEE in these children could be found. The
      question of electric accident during pregnancy should be considered when
      documenting the history of children with Ohtahara syndrome.

PMID- 11504610
TI  - Nicotinic receptors in wonderland.

PMID- 11504611
TI  - Complex networks of interactions connect genes to phenotypes.

PMID- 11504612
TI  - A novel superfamily of enzymes that catalyze the modification of guanidino
      groups.
AB  - Three enzymes, peptidyl-arginine deiminase from Porphyromonas gingivalis,
      arginine deiminase and amidinotransferase are traditionally classified
      separately. By combining PSI-BLAST and FUGUE, data presented in this article
      describe how these enzymes belong to a novel superfamily, adopting a common fold
      and sharing similar catalytic mechanisms.

PMID- 11504613
TI  - Sialic acid synthase: the origin of fish type III antifreeze protein?
AB  - Fish type III antifreeze protein is homologous to the C-terminal region of
      mammalian sialic acid synthase. Similarity is greatest in the protein core and
      the flat ice-binding region. This relationship adds to the growing list of links
      between ice-binding proteins (antifreezes) and proteins that interact with sugars
      and polysaccharides.

PMID- 11504614
TI  - Stopwatch fluorescence: keeping time with DsRed.

PMID- 11504615
TI  - TonB--a mediator of iron uptake in bacteria.

PMID- 11504616
TI  - Hereditary haemochromatosis: more causative genes.

PMID- 11504623
TI  - The death domain superfamily: a tale of two interfaces?
AB  - The death domain superfamily, composed of the death domain (DD), death effector
      domain (DED) and caspase recruitment domain (CARD) families of proteins, plays a
      pivotal role in signaling events that regulate apoptosis. This review compares
      and contrasts the ten superfamily members with known structures. In particular,
      the two heterodimerization modes described to date, the CARD-CARD interaction
      between human Apaf-1 and procaspase 9, and the DD-DD interaction between
      Drosophila Pelle and Tube, are examined. The dimerization modes are strikingly
      different and, importantly, are not mutually exclusive. In fact, a trimer can be
      formed using both interactions.

PMID- 11504624
TI  - Coordination of Ca2+ signalling by NAADP.
AB  - Nicotinic acid adenine dinucleotide phosphate (NAADP) mobilizes intracellular
      Ca2+ stores in several cell types. Ample evidence suggests that NAADP activates
      intracellular Ca2+ channels distinct from those that are sensitive to inositol
      trisphosphate and ryanodine/cyclic ADP-ribose. Recent studies in intact cells
      have demonstrated functional coupling ('channel chatter') between Ca2+ release
      pathways mediated by NAADP, inositol trisphosphate and cyclic ADP-ribose. Thus,
      NAADP is probably an important determinant in shaping cytosolic Ca2+ signals.

PMID- 11504625
TI  - Journey of the iodide transporter NIS: from its molecular identification to its
      clinical role in cancer.
AB  - The Na+/I- symporter (NIS) is an intrinsic plasma membrane protein that mediates
      the active transport of I- in the thyroid, lactating mammary gland, stomach and
      salivary glands. The presence of NIS in the thyroid is exploited in diagnostic
      scintigraphic imaging and radioiodide therapy in thyroid cancer. The continued
      rapid progress in NIS research (aimed at the elucidation of the Na+-dependent I-
      transport mechanism, the analysis of NIS structure-function relations and the
      study of the tissue-specific regulation of NIS at all levels), holds potentially
      far-reaching medical applications beyond thyroid disease, in breast cancer and
      malignancies in other tissues.

PMID- 11504626
TI  - Enzyme catalysis: removing chemically 'essential' residues by site-directed
      mutagenesis.
AB  - Enzymatic catalysis relies on the action of the amino acid side chains arrayed in
      the enzyme active sites. Usually, only two or three 'essential' residues are
      directly involved in the bond making and breaking steps leading to product
      formation. For the past 20 years, enzymologists have been addressing the role of
      such residues by changing them into chemically inert side chains. Removal of an
      'essential' group often does not abolish activity, but can significantly alter
      the catalytic mechanism. Such results underscore the sophistication of enzyme
      catalysis and the functional plasticity of enzyme active sites.

PMID- 11504627
TI  - The glucose-regulated proteins: stress induction and clinical applications.
AB  - A protective mechanism used by cells to adapt to stress of the endoplasmic
      reticulum (ER) is the induction of members of the glucose-regulated protein (Grp)
      family. The induction of mammalian Grp proteins in response to ER stress involves
      a complex network of regulators and novel mechanisms. The elucidation of Grp
      function and regulation opens up new therapeutic approaches to diseases
      associated with ER stress and cancer.

PMID- 11504628
TI  - The crystallization and structural determination of tRNA.

PMID- 11504629
TI  - Comparisons of gene colinearity in genomes using GeneOrder2.0.
AB  - Comparative genomics is enhanced by data mining the rapidly expanding DNA
      sequence databases. Because of the immense amount of data, computational tools
      and methods are needed to augment traditional manual visualizations and
      manipulations of these data. GeneOrder2.0, a Java-based interactive software
      programme, organizes genome sequence data into tabular and graphical
      visualizations of the extent of colinearity of genes between any two chromosome
      genomes of < or =250 kilobases. Both GenBank and proprietary data can be analyzed
      with this tool.

PMID- 11504630
TI  - Synthesis and biological evaluation of methoxyphenyl porphyrin derivatives as
      potential photodynamic agents.
AB  - A new meso-2,4,6-trimethoxyphenyl porphyrin covalently linked to a 2',6'-dinitro
      4'-trifluoromethylphenyl group by an amine bond 5 and its metal complex with
      Cd(II) 6 was prepared. The photodynamic activities of 5 and 6 were evaluated in
      vitro on Hep-2 cells. A considerable increase in the photocytotoxic effect was
      found for 6, which has higher singlet molecular oxygen, O(2)((1)Delta(g)),
      production.

PMID- 11504631
TI  - Thermodynamic quantitative structure-activity relationship analysis for enzyme
      ligand interactions in aqueous phosphate buffer and organic solvent.
AB  - Thermodynamic quantitative structure-activity relationships (QSAR) for
      chymotrypsin-ligand binding is developed, and the results are compared for the
      effects of organic solvent on the substrate specificity of the enzymes to those
      in aqueous phosphate buffer. This is the first of such analysis utilizing
      thermodynamic QSAR. A possible explanation for the difference describing the
      effects of organic solvent for the binding of substituted phenyl esters of N
      benzoyl L-alanine analogues [PhCONHCH(Me)COOC(6)H(4)-p-X, I] observed in both the
      classical and the thermodynamic QSAR is presented.

PMID- 11504632
TI  - Effects of a 3-alkyl-, 4-hydroxy- and/or 8-aromatic-substituent on the
      phenylethanolamine N-methyltransferase inhibitor potency and alpha2-adrenoceptor
      affinity of 2,3,4,5-tetrahydro-1H-2-benzazepines.
AB  - 2,3,4,5-Tetrahydro-1H-2-benzazepine (THBA; 1) is nearly 100-fold more selective
      an inhibitor of phenylethanolamine N-methyltransferase (PNMT, EC 2.1.1.28) versus
      the alpha2-adrenoceptor than is 1,2,3,4-tetrahydroisoquinoline (THIQ; 2) (1: PNMT
      K(i)= 3.3 microM, alpha2-adrenoceptor K(i) = 11 microM, selectivity [alpha2
      K(i)/PNMT K(i)] = 3.3; 2: PNMT K(i) = 9.7 microM, alpha2 K(i) = 0.35 microM,
      selectivity=0.036;). Since the PNMT inhibitory activity and selectivity of THIQ
      were enhanced by the introduction of a hydrophilic electron-withdrawing 7
      substituent and a 3-alkyl-substituent, a similar study was conducted on THBA. 8
      Nitro-THBA (3) was found to be as potent an inhibitor of PNMT as its THIQ
      analogue (21) and to be more selective due to its reduced alpha2-adrenoceptor
      affinity (3: PNMT K(i) = 0.39 microM, alpha2 K(i) = 66 microM, selectivity = 170;
      21: PNMT K(i) = 0.41 microM, alpha2 K(i) = 4.3 microM, selectivity = 10).
      Introduction of a 3-alkyl substituent on the THBA nucleus decreased both the
      alpha2-adrenoceptor affinity and the PNMT inhibitory activity, suggesting an area
      of steric bulk intolerance at both sites. 4-Hydroxy-THBA (15), which can be
      considered a conformationally-restricted analogue of 3-hydroxymethyl-THIQ (30),
      exhibited poorer PNMT inhibitory activity and less selectivity than 30 (15: PNMT
      K(i) = 58 microM, alpha2 K(i) = 100 microM, selectivity = 1.7; 30: PNMT K(i) =
      1.1 microM, alpha2 K(i) = 6.6 microM, selectivity = 6.0). While the addition of
      an 8-nitro group to 15 increased the selectivity of 16 as compared to its THIQ
      analogue (31), it was not as potent at PNMT nor as selective as 8-nitro-THBA (3)
      (16, PNMT K(i) = 5.3 microM, alpha2 K(i) = 680 microM, selectivity = 130; 31:
      PNMT K(i) = 0.29 microM, alpha2 K(i) = 19 microM, selectivity = 66). Compound 3
      is the most selective (PNMT/alpha2) and one of the more potent at PNMT compounds
      yet reported in the benzazepine series, and should have sufficient lipophilicity
      to penetrate the blood-brain barrier (CLogP = 1.8).

PMID- 11504633
TI  - Tubulins in the primate retina: evidence that xanthophylls may be endogenous
      ligands for the paclitaxel-binding site.
AB  - The xanthophylls-lutein, zeaxanthin, and meso-zeaxanthin (L&Z)-are found in the
      central region of the primate retina, which is called the macula lutea (yellow
      spot). How they are anchored there and what their function is has been debated
      for over 50 years. Here, we present evidence that they may be bound to the
      paclitaxel (Taxol) binding site of the beta-tubulin subunit of microtubules and
      that a major function may be to modulate the dynamic instability of microtubules
      in the macula. Also, we compare nucleic acid and amino acid sequences of tubulins
      that are in human brain with those we have isolated from human-retina and monkey
      macula cDNA libraries. In so doing, we suggest that in primates, class I beta
      tubulin consists of at least two subtypes (beta(Ia) and beta(Ib)). Alignment
      analysis of the sequences of the genes for beta(Ia) and beta(Ib) indicates that
      the corresponding mRNAs may have other functions in addition to that of coding
      for proteins. Furthermore, we show that there are at least five different types
      of beta-tubulin in the macula lutea of rhesus monkey.

PMID- 11504634
TI  - Structure-activity relationship of cinnamic acylsulfonamide analogues on the
      human EP3 prostanoid receptor.
AB  - Potent and selective antagonists of the human EP3 receptor have been identified.
      The structure-activity relationship of the chemical series was conducted and we
      found several analogues displaying sub-nanomolar K(i) values at the EP3 receptor
      and micromolar activities at the EP1, EP2 and EP4 receptors. The effect of added
      human serum albumin (HSA) on the binding affinity at the EP3 receptor was also
      investigated.

PMID- 11504635
TI  - Microbial and reducing agents catalyze the rearrangement of taxanes.
AB  - 5alpha, 7beta, 9alpha, 10beta, 13alpha-Pentahydroxy-4(20),11(12)-taxadiene
      derivative 1 was converted to two unprecedented 1(15-->11)abeo-taxanes and a
      taxane derivative with a C10-C11 double bond by Absidia coerula ATCC 10738a. A
      similar compound was obtained from treatment with zinc of a triacetoxy
      4(20),11(12)-taxadiene derivative.

PMID- 11504636
TI  - Synthesis and QSAR studies of 4-substituted phenyl-2,6-dimethyl-3, 5-bis-N
      (substituted phenyl)carbamoyl-1,4-dihydropyridines as potential antitubercular
      agents.
AB  - Synthesis and QSAR studies of the title compounds have resulted in the
      identification of structural and physicochemical parameters (MR, sigma(o),
      sigma(m), sigma(p)) contributing to antitubercular activity. Among these,
      carbamoyl phenyl ring substituted at 3 and 4 position with NO(2) group or 2
      position with Cl or OCH(3) group shows >90% inhibition against H(37)Rnu
      comparable to other substituted phenyls.

PMID- 11504637
TI  - In vitro antifungal evaluation and structure-activity relationships of a new
      series of chalcone derivatives and synthetic analogues, with inhibitory
      properties against polymers of the fungal cell wall.
AB  - Here we report the synthesis, in vitro antifungal evaluation and SAR study of 41
      chalcones and analogues. In addition, all active structures were tested for their
      capacity of inhibiting Saccharomyces cerevisiae beta(1,3)-glucan synthase and
      chitin synthase, enzymes that catalyze the synthesis of the major polymers of the
      fungal cell wall.

PMID- 11504638
TI  - The synthesis and screening of 1,4,5,8-naphthalenetetracarboxylic diimide-peptide
      conjugates with antibacterial activity.
AB  - We have employed an initial combinatorial approach followed by systematic lead
      optimization to investigate a series of novel molecules that exhibit
      antimicrobial activity against Gram-negative and Gram-positive bacteria. The new
      molecules contain various sequences of amino acids, generally L-lysine and
      glycine, attached to the 1,4,5,8-naphthalenetetracarboxylic diimide aromatic
      unit. Systematic structure-activity studies found that increasing positive charge
      enhanced activity and molecules containing one naphthalenetetracarboxylic diimide
      unit as well as at least seven lysine residues were optimum for antimicrobial
      activity. The naphthalenetetracarboxylic diimide derivatives were found to be
      inactive against mammalian cell lines, making them excellent antimicrobial
      candidates. Our results indicate that combining positive charge with aromatic
      and/or hydrophobic elements may be an interesting new approach to antimicrobial
      agents and adds an important new dimension to the field of cationic peptides.

PMID- 11504639
TI  - Synthesis and QSAR studies in 2-(N-aryl-N-aroyl)amino-4,5-dihydrothiazole
      derivatives as potential antithrombotic agents.
AB  - A series of 2-(N-aryl-N-aroyl)amino-4,5-dihydrothiazole derivatives have been
      synthesized via cyclocondensation of N-aryl thioureas with 2-bromoethylamine
      hydrobromide followed by the reaction of the product thus obtained with aroyl
      chlorides. Title compounds were evaluated for their antithrombotic activity in
      vivo in mice where one of these compound 29 provided 65% protection as compared
      to 77% protection offered by the standard Indomethacin. Quantitative Structure
      Activity Relationship (QSAR) studies were performed on these compounds using
      physicochemical (hydrophobic, electronic, steric) parameter as independent and
      antithrombic activity as dependent parameter, where antithrombotic activity
      correlated best (r > 0.8) with electronic parameters (F, sigma or mu) having high
      statistical significance > 99.9% (F(2,22)>15.0; F(2,22alpha:0.001)=11.0)
      suggesting that hydrophobic, steric and resonance factors are insignificant in
      this set of molecules for the activity.

PMID- 11504640
TI  - Design, synthesis, and evaluation of alpha-ketoheterocycles as class C beta
      lactamase inhibitors.
AB  - A series of specific alpha-ketoheterocycles (benzoxazole, thiazole, imidazole,
      tetrazole, and thiazole-4-carboxylate) has been synthesized in order to assess
      their potential as beta-lactamase inhibitors. The syntheses were achieved either
      by construction of the heterocycle (benzoxazole) from an appropriate alpha
      hydroxyimidate, followed by oxidation of the alcohol, or by direct reaction of
      methyl phenaceturate with a lithiated heterocycle. The properties of these
      compounds in aqueous solution are described and their inhibitory activity against
      beta-lactamases assessed. They did inhibit the class C beta-lactamase of
      Enterobacter cloacae P99 but not the TEM beta-lactamase. The most effective
      inhibitor of the former enzyme (K(i)=0.11 mM) was 5-(phenylacetylglycyl)
      tetrazole, probably because it is an anion at neutral pH. Interpretation of the
      results was aided by computational models of the tetrahedral adducts. Most of the
      compounds also inhibited alpha-chymotrypsin but not porcine pancreatic elastase.

PMID- 11504641
TI  - Novel (4-piperidin-1-yl)-phenyl sulfonamides as potent and selective human
      beta(3) agonists.
AB  - A series of novel (4-piperidin-1-yl)-phenyl sulfonamides was prepared and
      evaluated for their biological activity on the human beta(3)-adrenergic receptor
      (AR). Replacement of the 3,4-dihydroxyl group of the catechol moiety with 4
      hydroxyl-3-methyl sulfonamide on the left-hand side of the compounds resulted in
      a number of potent full agonists at the beta(3) receptor. Modification of the
      right-hand side of the compounds by incorporation of a free carboxylic acid
      resulted in a few potent human beta(3) agonists with low affinities for beta(1)-
      and beta(2)-ARs. N-Alkyl substitution on the 4-piperidin-1-yl-phenylamine further
      increased the beta(3) potency while maintaining the selectivity. For example,
      sulfonamide 48 is a potent full beta(3) agonist (EC(50)=0.004 microM, IA=1.0)
      with > 500-fold selectivity over beta(1)- and beta(2)-ARs.

PMID- 11504642
TI  - Synthesis and SAR of 5-, 6-, 7- and 8-aza analogues of 3-aryl-4-hydroxyquinolin
      2(1H)-one as NMDA/glycine site antagonists.
AB  - A series of 5-, 6-, 7- and 8-aza analogues of 3-aryl-4-hydroxyquinolin-2(1H)-one
      was synthesized and assayed as NMDA/glycine receptor antagonists. The in vitro
      potency of these antagonists was determined by displacement of the glycine site
      radioligand [(3)H]5,7-dicholorokynurenic acid ([(3)H]DCKA) in rat brain cortical
      membranes. Selected compounds were also tested for functional antagonism using
      electrophysiological assays in Xenopus oocytes expressing cloned NMDA receptor
      (NR) 1A/2C subunits. Among the 5-, 6-, 7-, and 8-aza-3-aryl-4-hydroxyquinoline
      2(1H)-ones investigated, 5-aza-7-chloro-4-hydroxy-3-(3-phenoxyphenyl)quinolin-2
      (1H)-one (13i) is the most potent antagonist, having an IC(50) value of 110 nM in
      [(3)H]DCKA binding and a K(b) of 11 nM in the electrophysiology assay. Compound
      13i is also an active anticonvulsant when administered systemically in the mouse
      maximum electroshock-induced seizure test (ED(50)=2.3mg/kg, IP).

PMID- 11504643
TI  - Toward the identification of selective modulators of protein kinase C (PKC)
      isozymes: establishment of a binding assay for PKC isozymes using synthetic C1
      peptide receptors and identification of the critical residues involved in the
      phorbol ester binding.
AB  - Conventional and novel protein kinase C (PKC) isozymes contain two cysteine-rich
      C1 domains (C1A and C1B), both of which are candidate phorbol-12,13-dibutyrate
      (PDBu) binding sites. We previously synthesized C1 peptides (of approximately 50
      residues) corresponding to all PKC isozymes and measured their PDBu binding
      affinity. While many of these peptide receptors exhibited PDBu affinities
      comparable to the respective complete isozyme, some of the C1A peptides could not
      be used because they undergo temperature dependent inactivation. This problem was
      however eliminated by 4 degrees C incubation or elongation of the 50-mer C1
      peptides at both N- and C-termini to increase their folding efficiency and
      stability. These findings enabled us to determine the K(d)'s of PDBu for all PKC
      C1 peptides (except for theta-C1A) and establish the value of these peptides as
      readily available, stable, and easily handled surrogates of the individual
      isozymes. The resultant C1 peptide receptor library can be used to screen for new
      ligands with PKC isozyme and importantly C1 domain selectivity. Most of the C1
      peptide receptors showed strong PDBu binding affinities with K(d)'s in the
      nanomolar range (0.45-7.4 nM). Two peptides (delta-C1A and theta-C1A) bound PDBu
      over 100-fold less tightly. To identify the residues that contribute to this
      affinity difference, several mutants of delta-C1A and theta-C1A were synthesized.
      Both the G9K mutant of delta-C1A and the P9K mutant of theta-C1A showed K(d)'s of
      2-3 nM. This approach provides a useful procedure to determine the role of each
      C1 domain of the PKC isozymes by point mutation.

PMID- 11504644
TI  - Stereoselective detoxification of chiral sarin and soman analogues by
      phosphotriesterase.
AB  - The catalytic activity of the bacterial phosphotriesterase (PTE) toward a series
      of chiral analogues of the chemical warfare agents sarin and soman was measured.
      Chemical procedures were developed for the chiral syntheses of the S(P)- and R(P)
      enantiomers of O-isopropyl p-nitrophenyl methylphosphonate (sarin analogue) in
      high enantiomeric excess. The R(P)-enantiomer of the sarin analogue (k(cat)=2600
      s(-1)) was the preferred substrate for the wild-type PTE relative to the
      corresponding S(P)-enantiomer (k(cat)=290 s(-1)). The observed stereoselectivity
      was reversed using the PTE mutant, I106A/F132A/H254Y where the k(cat) values for
      the R(P)- and S(P)-enantiomers were 410 and 4200 s(-1), respectively. A chemo
      enzymatic procedure was developed for the chiral synthesis of the four
      stereoisomers of O-pinacolyl p-nitrophenyl methylphosphonate (soman analogue)
      with high diastereomeric excess. The R(P)R(C)-stereoisomer of the soman analogue
      was the preferred substrate for PTE. The k(cat) values for the soman analogues
      were measured as follows: R(P)R(C,) 48 s(-1); R(P)S(C), 4.8 s(-1); S(P)R(C), 0.3
      s(-1), and S(P)S(C), 0.04 s(-1). With the I106A/F132A/H254Y mutant of PTE the
      stereoselectivity toward the chiral phosphorus center was reversed. With the
      triple mutant the k(cat) values for the soman analogues were found to be as
      follows: R(P)R(C,) 0.3 s(-1); R(P)S(C), 0.3 s(-1); S(P)R(C), 11s(-1), and
      S(P)S(C), 2.1 s(-1). Prior investigations have demonstrated that the S(P)
      enantiomers of sarin and soman are significantly more toxic than the R(P)
      enantiomers. This investigation has demonstrated that mutants of the wild-type
      PTE can be readily constructed with enhanced catalytic activities toward the most
      toxic stereoisomers of sarin and soman.

PMID- 11504645
TI  - Inhibition of major groove DNA binding bZIP proteins by positive patch
      polyamides.
AB  - Cell permeable synthetic ligands that bind to predetermined DNA sequences offer a
      chemical approach to gene regulation, provided inhibition of a broad range of DNA
      transcription factors can be achieved. DNA minor groove binding polyamides
      containing aminoalkyl substituents at the N-1 of a single pyrrole residue display
      inhibitory effects for a bZIP protein which binds exclusively in the DNA major
      groove. For major groove protein inhibition, specific protein-DNA contacts along
      the phosphate backbone were targeted with the positively charged dimethylamino
      substituent on the backbone of a minor groove binding polyamide hairpin.
      Remarkably, these polyamides bind DNA with enhanced affinity and uncompromised
      specificity when compared to polyamides with the aminoalkyl moiety at the C
      terminus. By adding bZIP transcription factors to the class of protein-DNA
      complexes that can be disrupted by minor groove binding ligands, these results
      may increase the functional utility of polyamides as regulators of gene
      expression.

PMID- 11504646
TI  - The structure of McN-5652.
AB  - The configuration of the diastereoisomers of 6-(4-methylthiophenyl)-1,2,3,5,6,10b
      hexahydropyrrolo[2,1-a]isoquinoline 1 (McN-5652) is determined and unequivocally
      assigned by NMR spectroscopy (NOE measurements) and an X-ray structural analysis
      of the trans diastereoisomer. The enantiomers of cis-1 are separated by
      preparative HPLC on a chiral phase. One of the enantiomers of cis-1 represents
      the precursor for imaging the serotonin 5-HT transporter with positron emission
      tomography (PET).

PMID- 11504647
TI  - Synthesis and human leukocyte elastase inhibitory evaluation of phosphate
      triesters and acyl phosphates of penam sulfides and sulfones.
AB  - The synthesis of 6,6-dibromo-3alpha-(diphenylphosphate)oxymethyl-2,2-dimethyl
      penam sulfone (3a), 6alpha-chloro-3alpha-(diphenylphosphate)oxymethyl-2,2
      dimethyl penam sulfone (3b), benzyl 6alpha-(diphenyl-phosphate)oxypenicillanate
      sulfone (4) and 6,6-dibromo-3alpha-(methylphosphate)carbonyl-2,2-dimethylpenam
      sulfone (12) are reported. When tested as inhibitors of human leukocyte elastase,
      the compound 4 proved to be the most active.

PMID- 11504648
TI  - Synthesis and pharmacological activity of metabolites of the 5-HT(4) receptor
      antagonist SB-207266.
AB  - Three metabolites of N-[(1-butyl-4-piperidinyl)methyl]-3,4-dihydro-2H-[1,3]
      oxazino[3,2_a]indole-10-carboxamide (SB-207266) (1) were synthesised and their
      pharmacological activity determined.

PMID- 11504649
TI  - Synthesis and SAR of 3- and 4-substituted quinolin-2-ones: discovery of mixed 5
      HT(1B)/5-HT(2A) receptor antagonists.
AB  - Quinolin-2-ones bearing a heteroaryl-piperazine linked by a two carbon chain at
      the 3- or 4-position were synthesised and evaluated as mixed 5-HT(1B)/5-HT(2A)
      receptor antagonists. Potent mixed antagonists were obtained with thieno[3,2
      c]pyridine derivatives. In this series, compound 2.1 (SL 65.0472) proved to be
      functional antagonist at both the 5-HT(2A) receptor (rat in vivo 5-HT-induced
      hypertension model) and the 5-HT(1B) receptor (dog in vitro saphenous vein
      assay).

PMID- 11504650
TI  - Design and synthesis of a cephalosporin-retinoic acid prodrug activated by a
      monoclonal antibody-beta-lactamase conjugate.
AB  - Two novel series of all-trans-beta-retinoic acid derivatives were synthesized and
      found to possess anticancer activity. The first series, cephalosporin 3'-retinoic
      esters 6 and 7 were, respectively, obtained by the condensation of all-trans-beta
      retinoic acid (2) with cephalosporins 4 and 5. The second series, 7
      (retinamido)cephalosporins 11 and 12, were synthesized, respectively, by the
      condensation of 2 with cephalosporins 9 and 10. These four heretofore undescribed
      compounds 6, 7, 11, and 12 showed inhibitory activity against murine leukemias
      (L1210 and P388), sarcoma 180, breast carcinoma (MCF7), and human T-lymphocytes
      (Molt4/C8 and CEM/0). They also inhibited squamous metaplasia and keratinization
      in tracheal organ cultures derived from vitamin-A-deficient hamsters. Moreover,
      cephalosporin 3'-retinoic ester 7 exhibited enhanced activity against
      keratinization with ED(50)=3.91 x 10(-11) M in the presence of a beta-lactamase
      from Staphylococcus aureus 95. A tumor targeting fusion protein (dsFv3-beta
      lactamase) was also used in conjunction with cephem-based retinoid 7 and the
      potency of 7 toward L1210, P388, and MCF7 was found to approach that of the free
      retinoic acid (2). In the presence of dsFv3-beta-lactamase, tumor cells were
      found to be much more susceptible to retinoid 7 than normal human embryonic lung
      cells. These notions provide a new approach to the use of beta-retinoic acid for
      antitumor therapy.

PMID- 11504651
TI  - 3-Arylsulphonyl-5-arylamino-1,3,4-thiadiazol-2(3H)ones as anti-inflammatory and
      analgesic agents.
AB  - Two series of 3-arylsulphonyl-5-arylamino-1,3,4-thiadiazol-2(3H)ones 2 with
      potential anti-inflammatory and analgesic activity were prepared and tested.
      Pharmacological results revealed that all the title compounds, endowed with an
      arylsulphonyl side chain, possess good antalgic activity and fair anti
      inflammatory properties. The analgesic profile of the two series, evaluated by
      the acetic acid writhing test, showed that compounds 2c, 2f and 2h, in
      particular, were the most active. Structure-activity relationships are briefly
      discussed.

PMID- 11504652
TI  - Cytotoxic activities of novel hexahydroindolizino[8,7-b]indole derivatives
      prepared by 1,3-dipolar cycloaddition reactions of 3,4-dihydro-beta-carboline
      ylides.
AB  - A series of 1-cyano and 2-cyanohexahydroindolizino[8,7-b]indole derivatives was
      prepared by 1,3-dipolar cycloaddition of acrylonitrile with ylides derived from
      3,4-dihydro-beta-carboline and its 6-methoxy, 6-benzyloxy, 9-methyl and 9-benzyl
      analogues. The products, together with their reduced 1- or 2-aminomethyl
      derivatives, were evaluated for cytotoxic activity in L1210 cancer cells.
      Compounds derived from 6-benzyloxy or 9-benzyl-3,4-dihydro-beta-carboline were
      found to be the most active, with IC(50)'s in the 2-50 microM range. Of these,
      two compounds, the 1- and 2-cyano 8-benzyloxyindolizino[8,7-b]indole derivatives
      20a and 20c, respectively, were found by cytometric flux analysis to stop cancer
      cell growth at the G(2)M and 8N (>G(2)M) stage of the cell cycle. These two
      compounds also showed no loss of cytotoxic activity in K562R cancer cells
      resistant to doxorubicin.

PMID- 11504653
TI  - Anti-HIV-1 activity of an antisense phosphorothioate oligonucleotide bearing
      imidazole and primary amine groups.
AB  - We have previously shown that RNA cleaving reagents with imidazole and primary
      amine groups on the 5'-end of antisense oligodeoxyribonucleotides could site
      specifically cleave CpA as the target sequence of the substrate tRNA in vitro. In
      this study, a RNA cleaving reagent, composed of imidazole and primary amine
      groups on an antisense phosphorothioate oligonucleotide (Im-anti-s-ODN), was
      synthesized and evaluated for anti-HIV-1 activity in MT-4 cells. The sequence of
      the Im-anti-s-ODN was designed to be complementary to the HIV-1 gag-mRNA and to
      bind adjacent to the CpA cleavage site position. Im-anti-s-ODN encapsulated with
      the transfection reagent, DMRIE-C, had higher anti-HIV-1 activity than the
      unmodified antisense phosphorothioate oligonucleotide (anti-s-ODN) at a 2 microM
      concentration. Furthermore, the Im-anti-ODN encapsulated with DMRIE-C conferred
      sequence-specific inhibition.

PMID- 11504654
TI  - Neuritogenic cerebrosides from an edible Chinese mushroom. Part 2: Structures of
      two additional termitomycesphins and activity enhancement of an inactive
      cerebroside by hydroxylation.
AB  - Termitomycesphins E and F, novel cerebrosides that are hydroxylated around the
      middle of the long-chain base (LCB), have been isolated from the edible Chinese
      mushroom Termitomyces albuminosus (Berk.) Heim. ('Jizong' in Chinese) together
      with termitomycesphins A-D, and shown to induce neuronal differentiation in rat
      PC12 cells. Their stereostructures have been determined based on their chemical
      derivatization and spectroscopic analysis. The major cerebroside obtained from
      the same mushroom was not hydroxylated around the middle of the LCB and was
      inactive against PC12 cells, suggesting the importance of the extra hydroxyl
      group on LCB. The Di- and tetrahydroxylation of this inactive cerebroside
      resulted in the enhancement of its neuritogenic activity.

PMID- 11504655
TI  - Synthesis and evaluation of bifunctional anti-HIV agents based on specific CXCR4
      antagonists-AZT conjugation.
AB  - We have previously found that T140, a 14-amino acid residue peptide, inhibits
      infection of target cells by T cell-line-tropic strains of HIV-1 (X4-HIV-1)
      through its specific binding to a chemokine receptor, CXCR4. Here, we report
      synthesis and evaluation of bifunctional anti-HIV compounds, which are composed
      of T140 analogues and a reverse transcriptase inhibitor, 3'-azido-3'
      deoxythymidine (AZT). Novel conjugated analogues have been proved to have the
      ability for controlled release of AZT in neutral aqueous media as well as mouse
      and feline sera, and high selectivity indexes (SIs, 50% cytotoxic
      concentration/50% effective concentration) caused by a synergistic effect of two
      different regenerating agents. Thus, these bifunctional compounds have several
      potential advantages. T140 analogues can possibly work as a carrier of AZT
      targeting T cells due to their specific affinity for CXCR4 on T cells. A
      synergistic effect by two types of regenerating agents may enable drug dosage to
      be reduced, and thus it may effectively suppress toxic side effects and the
      appearance of drug-resistant virus.

PMID- 11504656
TI  - The influence of glutathione and cysteine levels on the cytotoxicity of
      helenanolide type sesquiterpene lactones against KB cells.
AB  - The biological activities of sesquiterpene lactones have been attributed to their
      reactivity with the cysteine residues of functional proteins forming covalent
      bonds via Michael type addition. In the present study we investigated the
      influence of different L-cysteine (cys) and glutathione (GSH) concentrations on
      the cytotoxicity of the sesquiterpene lactones (STLs) helenalin, 11alpha,13
      dihydrohelenalin acetate and chamissonolide against KB cells. Due to the
      significantly higher reactivity of the alpha-methylene-gamma-lactone (ML) towards
      cys as compared with the cyclopentenone (CP) site at physiological pH, addition
      of 20, 50 and 100 molar equivalents of cys decreased the cytotoxicity of
      helenalin and chamissonolide, whereas the cytotoxicity of 11alpha,13
      dihydrohelenalin acetate remained unaffected. In contrast, the influence of GSH
      addition on the cytotoxicity of 11alpha,13-dihydrohelenalin acetate depends on
      the concentration of GSH added. Concentration-effect curves obtained for
      chamissonolide and GSH resembled the decline in cytotoxicity after cys addition.
      Helenalin showed a biphasic shape of the concentration-effect curve for the 100:1
      GSH/helenalin ratio resembling at higher doses the chamissonolide and in lower
      doses the 11alpha,13-dihydrohelenalin acetate curve at 50-fold excess. These
      results can be explained by the different reactivity and equilibrium conditions
      for thiol addition of the two reactive centers of bifunctional STLs in cellular
      test systems and verified a clear correlation between the different reactivity of
      their electrophilic centers and the observed biological effects in in-vitro cell
      systems.

PMID- 11504657
TI  - Diamine containing VLA-4 antagonists.
AB  - Design and synthesis of a library as potential VLA-4 antagonists has been
      accomplished, based around a proposed pharmacophoric model. Compounds possessing
      submicromolar potency were identified and structure-activity relationships were
      seen across the library. Further derivatisation produced compounds with IC(50)'s
      <10 nmol for inhibiting the VLA-4 mediated binding of fibronectin to RAMOS cells,
      providing an ideal starting point for a lead optimisation Programme.

PMID- 11504658
TI  - Nickel(II) 2,6-diacetylpyridine bis(isonicotinoylhydrazonate) and
      bis(benzoylhydrazonate) complexes: structure and antimycobacterial evaluation.
      Part XI.
AB  - The reaction of 2,6-diacetylpyridine (dap) and isonicotinoyl- or benzoylhydrazide
      leads to bishydrazones H(2)dapin (1a) and H(2)dapb (1b), respectively. The
      condensation can either take place as a bimolecular kinetic process between the
      two reactants or as a monomolecular metal-templated synthesis in the presence of
      nickel(II) ions. In the latter case the reaction products are charged 2,6
      diacetylpyridine bis(hydrazone) nickel(II) complexes, which can be easily
      deprotonated to neutral hydrazonates. Diffractometric analysis of one of these
      [Ni(dapb)](2) (8b) has shown a binuclear structure with two octahedral nickel(II)
      ions bridged by two helicoidal dap (bishydrazonates) in a spheroidal structure of
      C(2V) symmetry. The synthesized complexes 8 are promising as antimycobacterial
      agents against M. tuberculosis H37Rv. In particular, 8b displays significant
      activity (MIC=0.025 microg/mL) 10-fold higher than rifampin and equal to
      isoniazid, while its ligand is ineffective. Compound 8b is also capable of
      reducing HIV-induced cytopathogenic effect in human T(4 )lymphocytes.

PMID- 11504661
TI  - Reconstructing the skeleton with intermittent parathyroid hormone.
AB  - The aim of treating osteoporosis is to restore bone strength by increasing its
      mass and reconstructing its architecture. Antiresorptive drugs reduce bone
      remodeling, allowing more complete secondary mineralization of the existing bone;
      the mass, macro- and microarchitecture of the bone remains unchanged. Anabolic
      agents have the potential to achieve this goal. Parathyroid hormone (PTH) is
      famous for its catabolic actions. Its anabolic effects, known by a select few
      over 70 years ago, are finally being appreciated. There is widely reproduced and
      compelling evidence in a range of species made osteoporotic by gonadectomy that
      intermittent PTH administration restores bone strength by stimulating new bone
      formation on the periosteal (outer) and endosteal (inner) bone surfaces,
      enlarging bone diameter, thickening the cortices and existing trabeculae, and
      perhaps increasing trabecular numbers and their connectivity.

PMID- 11504667
TI  - Genetics and animal models of hypoparathyroidism.
AB  - Hypoparathyroidism is a heterogeneous group of disorders with diverse etiologies.
      During the past decade, major advances have been made towards unraveling the
      precise cellular and molecular mechanisms that underlie the pathogenesis of this
      endocrinopathy. Studies of patients afflicted with the disease and of genetically
      altered mice with strategically engineered mutations have paved new and exciting
      avenues of investigation into its causes. While focusing on these discoveries, we
      review areas of controversy and discuss possible approaches for their resolution.

PMID- 11504668
TI  - Histone deacetylase as a therapeutic target.
AB  - The maintenance of health depends on the coordinated and tightly regulated
      expression of genetic information. Certain forms of leukemia have become
      paradigms for the pathogenic role of aberrant repression of differentiation
      genes. In these acute leukemias, fusion proteins generated by chromosomal
      translocations no longer function as transcriptional activators, but instead
      repress target genes by recruiting histone deacetylases (HDACs). The potential
      benefit of HDAC inhibition has been established by the use of enzyme inhibitors
      in vitro and in a single reported case of experimental therapy. Because recently
      identified HDAC inhibitors appear to overcome many drawbacks of early inhibitory
      compounds in clinical use, the stage is set to test the therapeutic value of HDAC
      inhibition in leukemias and in other diseases, including solid tumors and
      aberrant hormonal signaling. This review summarizes the range of diseases
      expected to respond to HDAC inhibition.

PMID- 11504669
TI  - Monoclonality of endocrine tumours: What does it mean?
AB  - It is believed and hoped that clonality assignment of tumours predicts long-term
      behaviour, narrows the search for the putative pathogenic event or events,
      identifies the extent of involvement of surrounding and distant tissues and
      assesses the completeness of surgical clearance. It should define optimal
      therapeutic strategies, such as gene therapy, and the most fruitful directions
      for research. Because the histological characteristics that are central to
      establishing prognosis in most neoplasms are of limited value in endocrine
      tumours, the benefits of interpretation of clonality are potentially even more
      valuable and far-reaching in these tissues. So, can clonality be accurately
      defined and, if it can, can the distinction between a polyclonal expansion of
      cells that are simply 'obeying orders' and the presumed progeny of a single
      anarchic mutant be usefully made? This review comes to the conclusion that the
      answer is 'probably not'.

PMID- 11504670
TI  - Pathophysiological effects of aldosterone in cardiovascular tissues.
AB  - The advent of antihypertensive therapy has resulted in a significant decrease in
      cardiovascular morbidity and mortality. Nevertheless, the incidence of heart
      failure, stroke and end-stage renal failure continues to increase. This trend
      suggests that a mechanism, independent of hypertension, is responsible for end
      organ damage. Genetic and experimental models of hypertension have demonstrated
      that excess aldosterone induces severe injury in the heart, brain and kidneys,
      and that pharmacological antagonism of aldosterone or adrenalectomy markedly
      reduces myocardial injury, cerebral hemorrhage and renal vascular disease. In
      clinical studies, plasma aldosterone levels have been shown to correlate with
      left ventricular hypertrophy, stroke and renal dysfunction. Moreover, aldosterone
      antagonism has been shown to reduce morbidity and mortality in patients with
      heart failure. Thus, an increasing body of evidence now indicates that
      aldosterone is an independent risk factor for cardiovascular disease.

PMID- 11504671
TI  - Dietary cholesterol absorption; more than just bile.
AB  - Absorption of dietary cholesterol from the intestine is an important part of
      cholesterol homeostasis and represents the first step that allows dietary
      cholesterol to exert its metabolic effects. Although the role of bile salts in
      the initial absorption of dietary cholesterol, by the formation of emulsions, is
      readily appreciated, the recognition that other molecular mechanisms might govern
      this process is only recently gaining momentum. Not only does the intestine
      regulate the amount of dietary cholesterol that enters the body; it is very
      selective with regard to the sterols that are allowed in. The human intestine is
      responsible for absorbing a significant amount of cholesterol each day. In
      addition to approximately 0.5 g d(-1) of dietary cholesterol, many other sterols
      are also present in almost equal abundance in the normal diet. Approximately 0.4
      g of plant sterols, such as sitosterol, brassicasterol and avanesterol, are also
      present. However, the human body seems to allow only cholesterol to enter and
      remain in the body, with almost negligible amounts of plant sterols being
      retained. That specific molecular mechanisms are responsible for this behavior is
      supported by the identification of the genetic defect(s) in a rare disorder, beta
      sitosterolemia (MIM 210250), where this process is disrupted. Such studies are
      now beginning to throw light on sterol absorption and excretion and elucidate the
      molecular mechanisms that govern these processes.

PMID- 11504672
TI  - Estrogens and cell-cycle regulation in breast cancer.
AB  - Clinical and experimental data have established that the leading cause of
      sporadic female breast cancer is exposure to estrogens, predominantly 17beta
      estradiol. Recent advances in the understanding of cell-cycle control mechanisms
      have been applied to outline the molecular mechanisms through which estrogens
      regulate the cell cycle in cultured breast cancer cells, in particular, in MCF-7
      cells. Here, we discuss how estrogens exert control over several key G1 phase
      cell-cycle regulators, namely cyclin D1, Myc, Cdk2, Cdk4, Cdk inhibitors and
      Cdc25A. Although the molecular mechanisms underlying estrogenic regulation of G1
      phase regulators are far from clear, current evidence indicates that estrogens
      might regulate several key molecules required for S phase entry, this regulation
      being independent of cell-cycle transit per se.

PMID- 11504674
TI  - Lung surfactant and reactive oxygen-nitrogen species: antimicrobial activity and
      host-pathogen interactions.
AB  - Surfactant protein (SP) A and SP-D are members of the collectin superfamily. They
      are widely distributed within the lung, are capable of antigen recognition, and
      can discern self versus nonself. SPs recognize bacteria, fungi, and viruses by
      binding mannose and N-acetylglucosamine residues on microbial cell walls. SP-A
      has been shown to stimulate the respiratory burst as well as nitric oxide
      synthase expression by alveolar macrophages. Although nitric oxide (NO.) is a
      well-recognized microbicidal product of macrophages, the mechanism(s) by which
      NO. contributes to host defense remains undefined. The purpose of this symposium
      was to present current research pertaining to the specific role of SPs and
      reactive oxygen-nitrogen species in innate immunity. The symposium focused on the
      mechanisms of NO*-mediated toxicity for bacterial, human, and animal models of SP
      A- and NO.-mediated pathogen killing, microbial defense mechanisms against
      reactive oxygen-nitrogen species, specific examples and signaling pathways
      involved in the SP-A-mediated killing of pulmonary pathogens, the structure and
      binding of SP-A and SP-D to bacterial targets, and the immunoregulatory functions
      of SP-A.

PMID- 11504675
TI  - Intermittent hypoxia: cell to system.
AB  - This symposium was organized to present research dealing with the effects of
      intermittent hypoxia on cardiorespiratory systems and cellular mechanisms. The
      pattern of neural impulse activity has been shown to be critical in the induction
      of genes in neuronal cells and involves distinct signaling pathways. Mechanisms
      associated with different patterns of intermittent hypoxia might share similar
      mechanisms. Chronic intermittent hypoxia selectively augments carotid body
      sensitivity to hypoxia and causes long-lasting activation of sensory discharge.
      Intermittent hypoxia also activates hypoxia-inducible factor-1. Reactive oxygen
      species are critical in altering carotid body function and hypoxia-inducible
      factor-1 activation caused by intermittent hypoxia. Blockade of serotonin
      function in the spinal cord prevents long-term facilitation in respiratory motor
      output elicited by episodic hypoxia and requires de novo protein synthesis.
      Chronic intermittent hypoxia leads to sustained elevation in arterial blood
      pressure and is associated with upregulation of catecholaminergic and renin
      angiotensin systems and downregulation of nitric oxide synthases.

PMID- 11504676
TI  - Endothelial cellular response to altered shear stress.
AB  - Endothelial cells are normally exposed constantly to mechanical forces that
      significantly influence their phenotype. This symposium presented recent
      information concerning endothelial cell responses to shear stress associated with
      blood flow. Endothelial cell shear stress mechanosensors that have been proposed
      include membrane receptor kinases, integrins, G proteins, ion channels,
      intercellular junction proteins, membrane lipids (e.g., those associated with
      caveolae), and the cytoskeleton. These sensors are linked to signaling cascades
      that interact with or result in generation of reactive oxygen species, nitric
      oxide, and various transcription factors among other responses. Endothelial cells
      adapt to sustained shear stress, and either an increase or decrease from normal
      shear leads to signaling events. In vitro models for the study of endothelial
      cell responses must consider the pattern of shear stress (e.g., steady vs.
      oscillatory flow), the scaffold for cell growth (e.g., basement membrane or other
      cell types such as smooth muscle cells), and the extent of flow adaptation. These
      cellular responses have major relevance for understanding the pathophysiological
      effects of increased shear stress associated with hypertension or decreased shear
      stress associated with thrombotic occlusion.

PMID- 11504677
TI  - Prostaglandins and sepsis: still a fascinating topic despite almost 40 years of
      research.

PMID- 11504678
TI  - Selective inhibition of COX-2 improves early survival in murine endotoxemia but
      not in bacterial peritonitis.
AB  - Prostaglandins of the E series are believed to act as important mediators of
      several pathophysiological events that occur in sepsis. Studies were performed to
      evaluate the effect of cyclooxygenase (COX)-2-specific inhibition on the outcome
      in murine endotoxemia and cecal ligation and puncture (CLP). We observed a
      significant time-dependent upregulation of PGE(2) production in both blood and
      lung homogenates of mice administered lipopolysaccharide intraperitoneally, which
      was nearly completely suppressed by the administration of the COX-2 inhibitor NS
      398. Treatment with NS-398 significantly improved early but not late survival in
      lipopolysaccharide-challenged mice. On the contrary, elevated PGE(2) levels were
      found in bronchoalveolar lavage fluid but not in plasma of mice subjected to CLP
      (21 gauge). Pretreatment with NS-398 failed to significantly improve survival in
      CLP mice. No significant differences were noted in plasma or lung homogenate
      proinflammatory cytokine levels or lung neutrophil sequestration between the NS
      398-treated and control groups. These results demonstrate that selective COX-2
      inhibition confers early but not long-term benefits without affecting the
      expression of proinflammatory cytokines or the development of lung inflammation.

PMID- 11504679
TI  - Serine/threonine phosphatase 2B regulates protein kinase C-alpha activity and
      endothelial barrier function.

PMID- 11504680
TI  - Protein phosphatase 2B inhibitor potentiates endothelial PKC activity and barrier
      dysfunction.
AB  - Serine/threonine (Ser/Thr) protein phosphatases (PPs) are implicated in the
      recovery from endothelial barrier dysfunction caused by inflammatory mediators.
      We hypothesized that Ser/Thr PPs may regulate protein kinase C (PKC), a critical
      signaling molecule in barrier dysfunction, in the promotion of barrier recovery.
      Western analysis indicated that bovine pulmonary microvascular endothelial cells
      (BPMECs) expressed the three major Ser/Thr PPs, PP1, PP2A, and PP2B. Pretreatment
      with 100 ng/ml of FK506 (a PP2B inhibitor) but not with the PP1 and PP2A
      inhibitors calyculin A or okadaic acid potentiated the thrombin-induced increase
      in PKC phosphotransferase activity. FK506 also potentiated thrombin-induced PKC
      alpha but not PKC-beta phosphorylation. FK506 but not calyculin A or okadaic acid
      inhibited recovery from the thrombin-induced decrease in transendothelial
      resistance. Neither FK506 nor okadaic acid altered the thrombin-induced
      resistance decrease, whereas calyculin A potentiated the decrease. Downregulation
      of PKC with phorbol 12-myristate 13-acetate rescued the FK506-mediated inhibition
      of recovery, which was consistent with the finding that the thrombin-induced
      phosphorylation of PKC-alpha was reduced during the recovery phase. These results
      indicated that PP2B may play a physiologically important role in returning
      endothelial barrier dysfunction to normal through the regulation of PKC.

PMID- 11504681
TI  - Serine proteases increase oxidative stress in lung cells.
AB  - Several serine proteases are directly cytotoxic. We investigated whether the
      cytotoxic effects of proteases are associated with increased levels of reactive
      oxygen species (ROS) in cells. We found that treatment of lung fibroblasts or
      bronchial epithelial cells with relatively high concentrations (0.1--100 U/ml) of
      neutrophil elastase, trypsin, and Pronase increased ROS levels in the
      mitochondria and cytoplasm. The protease-induced increase in ROS was associated
      with oxidative cellular injury as determined by generation of 8-hydroxy-2'
      deoxyguanosine and malonaldehyde plus 4-hydroxyalkenal. The protease-induced
      increase in ROS was not merely due to cell detachment because the proteases also
      caused an increase in ROS in suspended cells, which precluded attachment to the
      extracellular matrix. The protease-induced increase in ROS appears to contribute
      to cytotoxicity because cell death induced by proteases was attenuated by
      treatment with catalase, a decomposer of H(2)O(2), and accelerated by treatment
      with aminotriazole, a catalase inhibitor. These results suggest that several
      proteases increase oxidative stress, indicating a direct interaction between
      proteases and ROS in mediating cytotoxicity.

PMID- 11504682
TI  - Microtubule disassembly increases endothelial cell barrier dysfunction: role of
      MLC phosphorylation.
AB  - Endothelial cell (EC) barrier regulation is critically dependent on cytoskeletal
      components (microfilaments and microtubules). Because several edemagenic agents
      induce actomyosin-driven EC contraction tightly linked to myosin light chain
      (MLC) phosphorylation and microfilament reorganization, we examined the role of
      microtubule components in bovine EC barrier regulation. Nocodazole or
      vinblastine, inhibitors of microtubule polymerization, significantly decreased
      transendothelial electrical resistance in a dose-dependent manner, whereas
      pretreatment with the microtubule stabilizer paclitaxel significantly attenuated
      this effect. Decreases in transendothelial electrical resistance induced by
      microtubule disruption correlated with increases in lung permeability in isolated
      ferret lung preparations as well as with increases in EC stress fiber content and
      MLC phosphorylation. The increases in MLC phosphorylation were attributed to
      decreases in myosin-specific phosphatase activity without significant increases
      in MLC kinase activity and were attenuated by paclitaxel or by several strategies
      (C3 exotoxin, toxin B, Rho kinase inhibition) to inhibit Rho GTPase. Together,
      these results suggest that microtubule disruption initiates specific signaling
      pathways that cross talk with microfilament networks, resulting in Rho-mediated
      EC contractility and barrier dysfunction.

PMID- 11504683
TI  - Chronic ethanol downregulates PKA activation and ciliary beating in bovine
      bronchial epithelial cells.
AB  - Previously, we reported that ethanol (EtOH) stimulates a rapid increase in
      ciliary beat frequency (CBF) of bovine bronchial epithelial cells (BBEC). Agents
      activating cAMP-dependent protein kinase (PKA) also stimulate CBF. EtOH
      stimulates BBEC CBF through cyclic nucleotide kinase activation. However, EtOH
      stimulated CBF is maximal by 1 h and subsides by 6 h, returning to baseline by 24
      h. We hypothesized that the loss of EtOH-stimulated CBF was a result of
      downregulation of PKA activity. To determine the PKA activation state in response
      to EtOH, ciliated BBEC were stimulated for 0--72 h with various concentrations of
      EtOH and assayed for PKA. EtOH (100 mM) treatment of the cells for 1 h increased
      PKA activity threefold over unstimulated controls. PKA activity decreased with
      increasing time from 6 to 24 h. When BBEC were preincubated with 100 mM EtOH for
      24 h, the stimulation of PKA by isoproterenol or 8-bromo-cAMP was abrogated. EtOH
      desensitizes BBEC to PKA-activating agents, suggesting that EtOH rapidly
      stimulates, whereas long-term EtOH downregulates, CBF via PKA in BBEC.

PMID- 11504684
TI  - Differential expression of Tie-2 receptors and angiopoietins in response to in
      vivo hypoxia in rats.
AB  - In this study, we assessed the effects of in vivo hypoxia on the expression of
      Tie-2 receptors and angiopoietins in various organs of conscious rats and
      correlated these effects with the expression of hypoxia-inducible factor-1 (HIF
      1). RT-PCR and Southern blotting were used to amplify mRNA expression of
      angiopoietin-1, -2, and -3, Tie-2, and HIF-1 alpha in tissues of normoxic and
      hypoxic (fraction of inspired oxygen of 9--10% for either 12 or 48 h) rats.
      Hypoxia provoked a decline in angiopoietin-1 mRNA and Tie-2 mRNA, protein, and
      phosphorylation levels in the lung, liver, cerebellum, and heart but not in the
      kidney and diaphragm. In comparison, hypoxia raised the levels of angiopoietin-2
      mRNA in the cerebellum and angiopoietin-3 mRNA in the lung, kidney, and
      diaphragm. HIF-1 alpha mRNA was abundant in most organs of normoxic rats but was
      significantly induced in the kidney and diaphragm of hypoxic rats. We conclude
      that in vivo hypoxia exerts inhibitory effects on the activity of the
      angiopoietin-1/Tie-2 receptor pathway through reduction of angiopoietin-1 and
      upregulation of angiopoietin-2 and -3. Induction of angiopoietin-3 in the kidney
      and diaphragm of hypoxic rats could be mediated through the HIF-1 transcription
      factor.

PMID- 11504685
TI  - Alveolar fluid reabsorption is impaired by increased left atrial pressures in
      rats.
AB  - Cardiogenic pulmonary edema results from increased hydrostatic pressures across
      the pulmonary circulation. We studied active Na(+) transport and alveolar fluid
      reabsorption in isolated perfused rat lungs exposed to increasing levels of left
      atrial pressure (LAP; 0--20 cmH(2)O) for 60 min. Active Na(+) transport and fluid
      reabsorption did not change when LAP was increased to 5 and 10 cmH(2)O compared
      with that in the control group (0 cmH(2)O; 0.50 +/- 0.02 ml/h). However, alveolar
      fluid reabsorption decreased by approximately 50% in rat lungs in which the LAP
      was raised to 15 cmH(2)O (0.25 +/- 0.03 ml/h). The passive movement of small
      solutes ((22)Na(+) and [(3)H]mannitol) and large solutes (FITC-albumin) increased
      progressively in rats exposed to higher LAP. There was no significant edema in
      lungs with a LAP of 15 cmH(2)O when all active Na(+) transport was inhibited by
      hypothermia or amiloride (10(-4) M) and ouabain (5 x 10(-4) M). However, when LAP
      was increased to 20 cmH(2)O, there was a significant influx of fluid (-0.69 +/-
      0.10 ml/h), precluding the ability to assess the rate of fluid reabsorption. In
      additional studies, LAP was decreased from 15 to 0 cmH(2)O in the second and
      third hours of the experimental protocol, which resulted in normalization of lung
      permeability to solutes and alveolar fluid reabsorption. These data suggest that
      in an increased LAP model, the changes in clearance and permeability are
      transient, reversible, and directly related to high pulmonary circulation
      pressures.

PMID- 11504686
TI  - Adenoviral E1A primes alveolar epithelial cells to PM(10)-induced transcription
      of interleukin-8.
AB  - The presence of the adenoviral early region 1A (E1A) protein in human lungs has
      been associated with an increased risk of chronic obstructive pulmonary disease
      (COPD), possibly by a mechanism involving amplification of proinflammatory
      responses. We hypothesize that enhanced inflammation results from increased
      transcription factor activation in E1A-carrying cells, which may afford
      susceptibility to environmental particulate matter < 10 microm (PM(10))-mediated
      oxidative stress. We measured interleukin (IL)-8 mRNA expression and protein
      release in human alveolar epithelial cells (A549) transfected with the E1A gene
      (E1A+ve). Both E1A+ve and -ve cells released IL-8 after incubation with TNF
      alpha, but only E1A+ve cells were sensitive to LPS stimulation in IL-8 mRNA
      expression and protein release. E1A+ve cells showed an enhanced IL-8 mRNA and
      protein response after treatment with H(2)O(2) and PM(10). E1A-enhanced induction
      of IL-8 was accompanied by increases in activator protein-1 and nuclear factor
      kappa B nuclear binding in E1A+ve cells, which also showed higher basal nuclear
      binding of these transcription factors. These data suggest that the presence of
      E1A primes the cell transcriptional machinery for oxidative stress signaling and
      therefore facilitates amplification of proinflammatory responses. By this
      mechanism, susceptibility to exacerbation of COPD in response to particulate air
      pollution may occur in individuals harboring E1A.

PMID- 11504687
TI  - Nickel requires hypoxia-inducible factor-1 alpha, not redox signaling, to induce
      plasminogen activator inhibitor-1.
AB  - Human epidemiological and animal studies have associated inhalation of nickel
      dusts with an increased incidence of pulmonary fibrosis. At the cellular level,
      particulate nickel subsulfide inhibits fibrinolysis by transcriptionally inducing
      expression of plasminogen activator inhibitor (PAI)-1, an inhibitor of the
      urokinase-type plasminogen activator. Because nickel is known to mimic hypoxia,
      the present study examined whether nickel transcriptionally activates PAI-1
      through the hypoxia-inducible factor (HIF)-1 alpha signaling pathway. The
      involvement of the NADPH oxidase complex, reactive oxygen species, and kinases in
      mediating nickel-induced HIF-1 alpha signaling was also investigated. Addition of
      nickel to BEAS-2B human airway epithelial cells increased HIF-1 alpha protein
      levels and elevated PAI-1 mRNA levels. Pretreatment of cells with the
      extracellular signal-regulated kinase inhibitor U-0126 partially blocked HIF-1
      alpha protein and PAI-1 mRNA levels induced by nickel, whereas antioxidants and
      NADPH oxidase inhibitors had no effect. Pretreating cells with antisense, but not
      sense, oligonucleotides to HIF-1 alpha mRNA abolished nickel-stimulated increases
      in PAI-1 mRNA. These data indicate that signaling through extracellular signal
      regulated kinase and HIF-1 alpha is required for nickel-induced transcriptional
      activation of PAI-1.

PMID- 11504688
TI  - AP-1-dependent induction of plasminogen activator inhibitor-1 by nickel does not
      require reactive oxygen.
AB  - Inhalation of nickel dust has been associated with an increased incidence of
      pulmonary fibrosis. Nickel may promote fibrosis by transcriptionally activating
      plasminogen activator inhibitor (PAI)-1 and inhibiting fibrinolysis. The current
      studies examined whether nickel stimulated the PAI-1 promoter though an oxidant
      sensitive activator protein (AP)-1 signaling pathway. Addition of nickel to BEAS
      2B human airway epithelial cells stimulated intracellular oxidation, induced c
      Jun and c-Fos mRNA levels, increased phospho- and total c-Jun protein levels, and
      elevated PAI-1 mRNA levels over a 24-h time course. Pretreatment of the cells
      with antioxidants did not affect increased c-Jun protein or PAI-1 mRNA levels.
      Expression of the dominant negative inhibitor of AP-1, TAM67, prevented nickel
      stimulated AP-1 DNA binding, AP-1-luciferase reporter construct activity, and PAI
      1 mRNA levels. Overexpression of c-Jun, however, failed to induce the AP-1
      luciferase reporter construct or PAI-1 mRNA levels. These data indicated that
      nickel activated AP-1 through an oxidant-independent pathway and that basal AP-1
      is necessary for nickel-induced expression of PAI-1.

PMID- 11504689
TI  - Norepinephrine induces alveolar epithelial apoptosis mediated by alpha-, beta-,
      and angiotensin receptor activation.
AB  - Norepinephrine (NE) induces apoptosis in cardiac myocytes, and autocrine
      production of angiotensin (ANG) II is required for apoptosis of alveolar
      epithelial cells (AECs) (Wang R, Zagariya A, Ang E, Ibarra-Sunga O, and Uhal BD.
      Am J Physiol Lung Cell Mol Physiol 277: L1245--L1250, 1999; Wang R, Alam G,
      Zagariya A, Gidea C, Pinillos H, Lalude O, Choudhary G, and Uhal BD. J Cell
      Physiol 185: 253--259, 2000). On this basis, we hypothesized that NE might induce
      apoptosis of AECs in a manner inhibitable by ANG system antagonists. Purified NE
      induced apoptosis in the human A549 AEC-derived cell line or in primary cultures
      of rat AECs, with EC(50) values of 200 and 20 nM, respectively. Neither the alpha
      agonist phenylephrine nor the beta-agonist isoproterenol could mimic NE when
      tested alone but when applied together could induce apoptosis with potency equal
      to NE. Apoptosis and net cell loss (47--59% in 40 h) in response to NE was
      completely abrogated by the ANG-converting enzyme inhibitor lisinopril or the ANG
      II receptor antagonist saralasin, each at concentrations capable of blocking Fas-
      or tumor necrosis factor-alpha-induced apoptosis. These data suggest that NE
      induces apoptosis of human and rat AECs through a mechanism involving the
      combination of alpha- and beta-adrenoceptor activation followed by autocrine
      generation of ANG II.

PMID- 11504690
TI  - Calcium sensitization produced by G protein activation in airway smooth muscle.
AB  - We determined whether activation of G proteins can affect the force developed for
      a given intracellular Ca(2+) concentration ([Ca(2+)]; i.e., the Ca(2+)
      sensitivity) by mechanisms in addition to changes in regulatory myosin light
      chain (rMLC) phosphorylation. Responses in alpha-toxin-permeabilized canine
      tracheal smooth muscle were determined with Ca(2+) alone or in the presence of
      ACh, endothelin-1 (ET-1), or aluminum fluoride (AlF; acute or 1-h exposure).
      Acute exposure to each compound increased Ca(2+) sensitivity without changing the
      response to high [Ca(2+)] (maximal force). However, chronic exposure to AlF, but
      not to chronic ACh or ET-1, increased maximal force by increasing the force
      produced for a given rMLC phosphorylation. Studies employing thiophosphorylation
      of rMLC showed that the increase in force produced by chronic AlF exposure
      required Ca(2+) during activation to be manifest. Unlike the acute response to
      receptor agonists, which is mediated solely by increases in rMLC phosphorylation,
      chronic direct activation of G proteins further increases Ca(2+) sensitivity in
      airways by additional mechanisms that are independent of rMLC phosphorylation.

PMID- 11504691
TI  - Mechanism of substance P-induced liquid secretion across bronchial epithelium.
AB  - The present study was undertaken to identify and determine the mechanism of
      noncholinergic pathways for the induction of liquid secretion across airway
      epithelium. Excised porcine bronchi secreted substantial and significant
      quantities of liquid when exposed to acetylcholine, substance P, or forskolin but
      not to isoproterenol, norepinephrine, or phenylephrine. Bumetanide, an inhibitor
      of Na(+)-K(+)-2Cl(-) cotransport, reduced the liquid secretion response to
      substance P by 69%. Approximately two-thirds of bumetanide-insensitive liquid
      secretion was blocked by dimethylamiloride (DMA), a Na(+)/H(+) exchange
      inhibitor. Substance P responses were preserved in airways after surface
      epithelium removal, suggesting that secreted liquid originated from submucosal
      glands. The anion channel blockers diphenylamine-2-carboxylate (DPC) and 5-nitro
      2-(3-phenylpropylamino)benzoic acid (NPPB) inhibited >90% of substance P-induced
      liquid secretion, whereas DIDS had no effect. DMA, DPC, and NPPB had greater
      inhibitory effects on net HCO(3)(-) secretion than on liquid secretion. Although
      preserved relative to liquid secretion, net HCO(3)(-) secretion was reduced by
      39% in the presence of bumetanide. We conclude that substance P induces liquid
      secretion from bronchial submucosal glands of pigs through active transport of
      Cl(-) and HCO(3)(-). The pattern of responses to secretion agonists and
      antagonists suggests that the cystic fibrosis transmembrane conductance regulator
      mediates this process.

PMID- 11504692
TI  - H(2)O(2) signals 5-HT-induced ERK MAP kinase activation and mitogenesis of smooth
      muscle cells.
AB  - Our previous studies have shown that 5-hydroxytryptamine (5-HT) induces cellular
      hyperplasia/hypertrophy through protein tyrosine phosphorylation, rapid formation
      of superoxide (O(2)(-)), and extracellular signal-regulated kinase (ERK)1/ERK2
      mitogen-activated protein (MAP) kinase activation. Intracellularly released O(2)(
      ) is rapidly dismuted by superoxide dismutase (SOD) to H(2)O(2), another possible
      cellular growth mediator. In the present study, we assessed whether H(2)O(2)
      participates in 5-HT-induced mitogenic signaling. Inactivation of cellular Cu/Zn
      SOD by copper-chelating agents inhibited 5-HT-induced DNA synthesis of bovine
      pulmonary artery smooth muscle cells (BPASMCs). Infection of BPASMCs with an
      adenovirus containing catalase inhibited both ERK1/ERK2 MAP kinase activation and
      DNA synthesis induced by 5-HT. Although we could not find evidence of p38 MAP
      kinase activation by 5-HT, SB-203580 and SB-202190, reported inhibitors of p38
      MAP kinase, inhibited the 5-HT-induced growth of BPASMCs. However, these
      inhibitors also inhibited 5-HT-induced O(2)(-) release. Thus quenching of O(2)(-)
      may be their mechanism for inhibition of cellular growth unrelated to p38 MAP
      kinase inhibition. These data indicate that generation of O(2)(-) in BPASMCs in
      response to 5-HT is followed by an increase in intracellular H(2)O(2) that
      mediates 5-HT-induced mitogenesis through activation of ERK1/ERK2 but not of p38
      MAP kinase.

PMID- 11504693
TI  - Intrinsic AHR in IL-5 transgenic mice is dependent on CD4(+) cells and CD49d
      mediated signaling.
AB  - Overexpression of interleukin (IL)-5 by the airway epithelium in mice using the
      rat CC10 promoter (NJ.1726 line) leads to several histopathologies characteristic
      of human asthma, including airway hyperreactivity (AHR). We investigated the
      contribution of B and T cells, as well as CD4 expression, to the development of
      AHR in IL-5 transgenic mice. NJ.1726 mice on a T cell or CD4 knockout background,
      but not on a B cell knockout background, lost intrinsic AHR. These effects
      occurred without decreases in IL-5 or eosinophils. We further investigated the
      contribution of alpha(4)-integrin signaling to the development of AHR in IL-5
      transgenic mice through the administration of anti-CD49d (alpha(4)-integrin)
      antibody (PS/2). Administration of PS/2 resulted in immediate (16-h) inhibition
      of AHR. The inhibition of AHR was not associated with a decrease in airway
      eosinophils. These studies demonstrate that, despite the presence of increased
      levels of IL-5 and eosinophils in the lungs of NJ.1726 mice, CD4(+) cells and
      alpha(4)-integrin signaling are necessary for the intrinsic AHR that develops in
      IL-5 transgenic mice.

PMID- 11504694
TI  - Surfactant proteins A and D in Eustachian tube epithelium.
AB  - Surfactant protein (SP) A and SP-D are collectins that have roles in host
      defense. The Eustachian tube (ET) maintains the patency between the upper airways
      and the middle ear. Dysfunction of local mucosal immunity in ET may predispose
      infants to recurrent otitis media. We recently described preliminary evidence of
      the expression of SP-A and SP-D in the ET. Our present aim was to establish the
      sites of SP-A and SP-D expression within the epithelium of the ET in vivo. With
      in situ hybridization, electron microscopy, and immunoelectron microscopy, the
      cells responsible for SP-A and SP-D expression and storage were identified. SP-A
      expression was localized within the ET epithelium, and the protein was found in
      the electron-dense granules of microvillar epithelial cells. Being concentrated
      in the epithelial lining, only a few cells revealed intracellular SP-D, and it
      was not associated with granules. The SP-A and SP-D immunoreactivities in ET
      lavage fluid, as shown by Western blot analyses, were similar to those in
      bronchoalveolar lavage fluid. We propose that there are specialized cells in the
      ET epithelium expressing and secreting SP-A and SP-D. SP-A and SP-D may be
      important for antibody-independent protection of the middle ear against
      infections.

PMID- 11504695
TI  - Airway inflammation in nonasthmatic amateur runners.
AB  - Elite athletes show a high prevalence of symptoms and signs of asthma, but no
      study has assessed the acute effects of endurance exercise on airway cells in
      nonasthmatic athletes. We measured exhaled nitric oxide (NO) and collected
      samples of induced sputum after 3% NaCl aerosol administration for 20 min in
      nonasthmatic middle-aged amateur runners after the Fourth Palermo International
      Marathon and 6--9 wk later (habitual training period) at baseline. After the
      marathon, exhaled NO (n = 9 subjects) was higher [27 +/- 9 parts/billion (ppb)]
      than at baseline (12 +/- 4 ppb; P < 0.0005). Polymorphonuclear neutrophil (PMN)
      counts in induced sputum were much higher in runners (91.2 +/- 3.6% of total
      cells postmarathon and 78.7 +/- 9.1% at baseline) than in sedentary control
      subjects (9.9 +/- 5.9%; P < 0.001). Expression of L-selectin and CD11b/CD18 in
      sputum PMNs was lower after the race than at baseline and inversely related to
      the amount of exhaled NO (r = -0.66 and -0.69, respectively; P < 0.05). Our data
      indicate that sputum PMNs are increased in nonasthmatic runners both after a
      marathon and at baseline and suggest that NO may modulate exercise-associated
      inflammatory airway changes.

PMID- 11504696
TI  - A low level of TNF-alpha mediates hemorrhage-induced acute lung injury via p55
      TNF receptor.
AB  - Acute lung injury after hemorrhagic shock (HS) is associated with the expression
      of tumor necrosis factor (TNF)-alpha in the lung. However, the role of TNF-alpha
      and its receptors in this pulmonary disorder remains obscure. This study examined
      the temporal relationship of pulmonary TNF-alpha production to neutrophil
      accumulation during HS and determined the role of TNF-alpha in neutrophil
      accumulation and lung leak. HS was induced in mice by removal of 30% of total
      blood volume. Lung TNF-alpha was measured by ELISA. Neutrophil accumulation was
      detected by immunofluorescent staining, and microvascular permeability was
      assessed using Evans blue dye. Although HS induced a slight and transient
      increase in lung TNF-alpha, neutrophil accumulation preceded the increase in TNF
      alpha. However, lung neutrophil accumulation and lung leak were abrogated in TNF
      alpha knockout mice, and both were restored by administration of recombinant TNF
      alpha to TNF-alpha knockout mice before HS. Neutrophil accumulation and lung leak
      were abrogated in mice lacking the p55 TNF-alpha receptor, but neither was
      influenced by p75 TNF-alpha receptor knockout. This study demonstrates that a low
      level of pulmonary TNF-alpha is sufficient to mediate HS-induced acute lung
      injury during HS and that the p55 TNF-alpha receptor plays a dominant role in
      regulating the pulmonary inflammatory response to HS.

PMID- 11504697
TI  - Respiratory distress after intratracheal bleomycin: selective deficiency of
      surfactant proteins B and C.
AB  - Intratracheal bleomycin in rats is associated with respiratory distress of
      uncertain etiology. We investigated the expression of surfactant components in
      this model of lung injury. Maximum respiratory distress, determined by
      respiratory rate, occurred at 7 days, and surfactant dysfunction was confirmed by
      increased surface tension of the large-aggregate fraction of bronchoalveolar
      lavage (BAL). In injured animals, phospholipid content and composition were
      similar to those of controls, mature surfactant protein (SP) B was decreased 90%,
      and SP-A and SP-D contents were increased. In lung tissue, SP-B and SP-C mRNAs
      were decreased by 2 days and maximally at 4--7 days and recovered between 14 and
      21 days after injury. Immunostaining of SP-B and proSP-C was decreased in type II
      epithelial cells but strong in macrophages. By electron microscopy, injured lungs
      had type II cells lacking lamellar bodies and macrophages with phagocytosed
      lamellar bodies. Surface activity of BAL phospholipids of injured animals was
      restored by addition of exogenous SP-B. We conclude that respiratory distress
      after bleomycin in rats results from surfactant dysfunction in part secondary to
      selective downregulation of SP-B and SP-C.

PMID- 11504698
TI  - SP-D and GM-CSF regulate surfactant homeostasis via distinct mechanisms.
AB  - Both surfactant protein (SP) D and granulocyte-macrophage colony-stimulating
      factor (GM-CSF) influence pulmonary surfactant homeostasis, with the deficiency
      of either protein causing marked accumulation of surfactant phospholipids in lung
      tissues and in the alveoli. To assess whether the effects of each gene were
      mediated by distinct or shared mechanisms, surfactant homeostasis and lung
      morphology were assessed in 1) double-transgenic mice in which both SP-D and GM
      CSF genes were ablated [SP-D(-/-),GM(-/-)] and 2) transgenic mice deficient in
      both SP-D and GM-CSF in which the expression of GM-CSF was increased in the lung.
      Saturated phosphatidylcholine (Sat PC) pool sizes were markedly increased in SP
      D(-/-),GM(-/-) mice, with the effects of each gene deletion on surfactant Sat PC
      pool sizes being approximately additive. Expression of GM-CSF in lungs of SP-D(-/
      ),GM(-/-) mice corrected GM-CSF-dependent abnormalities in surfactant catabolism
      but did not correct lung pathology characteristic of SP-D deletion. In contrast
      to findings in GM(-/-) mice, degradation of [(3)H]dipalmitoylphosphatidylcholine
      by alveolar macrophages from the SP-D(-/-) mice was normal. The emphysema and
      foamy macrophage infiltrates characteristic of SP-D(-/-) mice were similar in the
      presence or absence of GM-CSF. Taken together, these findings demonstrate the
      distinct roles of SP-D and GM-CSF in the regulation of surfactant homeostasis and
      lung structure.

PMID- 11504699
TI  - Persistent mucin glycoprotein alterations in equine recurrent airway obstruction.
AB  - Horses with the episodic asthmalike condition of recurrent airway obstruction
      (RAO) have bouts of inflammation and bronchoconstriction associated with indoor
      housing. To assess the potential differences in airway secretions between RAO
      affected and control horses, methods to quantify mucus secretions were developed
      and applied to bronchoalveolar lavage fluid. The relative difference in the
      amount of mucin glycoproteins between control and RAO-affected horses was
      assessed with a carbohydrate side chain-specific monoclonal antibody (4E4) in an
      enzyme-linked immunosorbent assay and by carbohydrate-specific enzyme-linked
      lectin assays. Significantly increased levels of 4E4-immunoreactive glycoprotein
      and the mucin-associated carbohydrates fucose (alpha-1,2 linkage) and N
      acetylglucosamine were detected in RAO-affected horses in acute disease. RAO
      affected horses in remission maintained significantly elevated levels of alpha
      1,2-fucose and N-acetylglucosamine, whereas the 4E4-immunoreactive glycoprotein
      levels displayed a trend toward an increase over control levels. These results
      indicated that persistent changes in the quantity and/or quality of mucus
      glycoproteins occurred in the RAO-affected horses.

PMID- 11504700
TI  - Expression of CFTR and Cl(-) conductances in cells of pulmonary neuroepithelial
      bodies.
AB  - The pulmonary neuroendocrine cell system comprises solitary neuroendocrine cells
      and clusters of innervated cells or neuroepithelial bodies (NEBs). NEBs figure
      prominently during the perinatal period when they are postulated to be involved
      in physiological adaptation to air breathing. Previous studies have documented
      hyperplasia of NEBs in cystic fibrosis (CF) lungs and increased neuropeptide
      (bombesin) content produced by these cells, possibly secondary to chronic hypoxia
      related to CF lung disease. However, little is known about the role of NEBs in
      the pathogenesis of CF lung disease. In the present study, using a panel of
      cystic fibrosis transmembrane conductance regulator (CFTR)-specific antibodies
      and confocal microscopy in combination with RT-PCR, we demonstrate expression of
      CFTR message and protein in NEB cells of rabbit neonatal lungs. NEB cells
      expressed CFTR along with neuroendocrine markers. Confocal microscopy established
      apical membrane localization of the CFTR protein in NEB cells. Cl(-) conductances
      corresponding to functional CFTR were demonstrated in NEB cells in a fresh lung
      slice preparation. Our findings suggest that NEBs, and related neuroendocrine
      mechanisms, likely play a role in the pathogenesis of CF lung disease, including
      the early stages before establishment of chronic infection and chronic lung
      disease.

PMID- 11504701
TI  - Lack of amiloride-sensitive transport across alveolar and respiratory epithelium
      of iNOS(-/-) mice in vivo.
AB  - The extent to which endogenously generated nitric oxide alters Na(+) transport
      across the mammalian alveolar epithelium in vivo has not been documented. Herein
      we measured alveolar fluid clearance and nasal potential differences in mice
      lacking the inducible form of nitric oxide synthase [iNOS; iNOS(-/-)] and their
      corresponding wild-type controls [iNOS(+/+)]. Alveolar fluid clearance values in
      iNOS(+/+) and iNOS(-/-) anesthetized mice with normal oxygenation and acid-base
      balance were ~30% of instilled fluid/30 min. In both groups of mice, fluid
      absorption was dependent on vectorial Na(+) movement. Amiloride (1.5 mM)
      decreased alveolar fluid clearance in iNOS(+/+) mice by 61%, whereas forskolin
      (50 microM) increased alveolar fluid clearance by 55% by stimulating amiloride
      insensitive pathways. Neither agent altered alveolar fluid clearance in iNOS(-/-)
      mice. Hyperoxia upregulated iNOS expression in iNOS(+/+) mice and decreased their
      amiloride-sensitive component of alveolar fluid clearance but had no effect on
      the corresponding values in iNOS(-/-) mice. Nasal potential difference
      measurements were consistent with alveolar fluid clearance in that both groups of
      mice had similar baseline values, which were amiloride sensitive in the iNOS(+/+)
      but not in the iNOS(-/-) mice. These data suggest that nitric oxide produced by
      iNOS under basal conditions plays an important role in regulating amiloride
      sensitive Na(+) channels in alveolar and airway epithelia.

PMID- 11504702
TI  - Inhibition of neutrophil apoptosis by acrolein: a mechanism of tobacco-related
      lung disease?
AB  - Cigarette smoking is known to contribute to inflammatory diseases of the
      respiratory tract by promoting recruitment of inflammatory-immune cells such as
      neutrophils and perhaps by altering neutrophil functional properties. We
      investigated whether acrolein, a toxic unsaturated aldehyde found in cigarette
      smoke, could directly affect neutrophil function. Exposure of freshly isolated
      human neutrophils to acrolein markedly inhibited spontaneous neutrophil apoptosis
      as indicated by loss of membrane asymmetry and DNA fragmentation and induced
      increased neutrophil production of the chemokine interleukin-8 (IL-8). Acrolein
      (1--50 microM) was found to induce marked activation of extracellular signal
      regulated kinase (ERK) and p38 mitogen-activated protein kinases (MAPKs), and
      inhibition of p38 MAPK activation by SB-203580 prevented acrolein-induced IL-8
      release. However, inhibition of either ERK or p38 MAPK did not affect acrolein
      dependent inhibition of apoptosis. Acrolein exposure prevented the activation of
      caspase-3, a crucial step in the execution of neutrophil apoptosis, presumably by
      direct inhibition of the enzyme. Our results indicate that acrolein may
      contribute to smoke-induced inflammatory processes in the lung by increasing
      neutrophil recruitment and reducing neutrophil clearance by apoptosis.

PMID- 11504703
TI  - G551D CF mice display an abnormal host response and have impaired clearance of
      Pseudomonas lung disease.
AB  - Several cystic fibrosis (CF) mouse models demonstrate an increased susceptibility
      to Pseudomonas aeruginosa lung infection, characterized by excessive inflammation
      and high rates of mortality. Here we developed a model of chronic P. aeruginosa
      lung disease in mice homozygous for the murine CF transmembrane conductance
      regulator G551D mutation that provides an excellent model for CF lung disease.
      After 3 days of infection with mucoid P. aeruginosa entrapped in agar beads, the
      G551D animals lost substantially more body weight than non-CF control animals and
      were less able to control the infection, harboring over 40-fold more bacteria in
      the lung. The airways of infected G551D animals contained altered concentrations
      of the inflammatory mediators tumor necrosis factor-alpha, KC/N51, and macrophage
      inflammatory protein-2 during the first 2 days of infection, suggesting that an
      ineffective inflammatory response is partly responsible for the clearance defect.

PMID- 11504704
TI  - Cyclin-dependent kinase inhibitors in the development of the central nervous
      system.

PMID- 11504705
TI  - Molecular mechanisms mediating mammalian mitogen-activated protein kinase (MAPK)
      kinase (MEK)-MAPK cell survival signals.

PMID- 11504706
TI  - The molecular chaperone Hsp90 is required for signal transduction by wild-type
      Hck and maintenance of its constitutively active counterpart.
AB  - We have investigated the relationship between the molecular chaperone heat shock
      protein-90 (Hsp90) and the signal transducing capacity of the Src-family kinase
      Hck. Inhibition of Hsp90 with geldanamycin suppressed the ability of bacterial
      lipopolysaccharide to enhance the cell adhesion properties of macrophages, a
      phenomenon most likely explained by the reduced expression and activity of Hck in
      macrophages lacking Hsp90 function. The contribution of Hsp90 to signal
      transduction by Hck was biochemically dissected further by examining its role in
      the de novo folding and maintenance of wild-type Hck and its constitutively
      active counterpart, Hck499F. The folding of nascent wild-type Hck and Hck499F
      into catalytically active conformations, and their accumulation in cells was
      found to be dependent on Hsp90 function. Notably, mature Hck499F had a greater
      requirement for on-going support from Hsp90 than did mature wild-type Hck. This
      particular finding might have important implications for our understanding of the
      evolution of oncogenic protein kinases.

PMID- 11504707
TI  - Role of increased basal expression of heat shock protein 72 in colonic epithelial
      c2BBE adenocarcinoma cells.
AB  - Although the expression of heat shock proteins (hsps) can be induced by a variety
      of stressful stimuli, certain neoplasms, including human intestinal T84, HT-29,
      and Caco2 adenocarcinoma cell lines, express constitutively high levels even
      under nonstress conditions. In this study, we examine the functional significance
      of increased hsp72 in spontaneously differentiating Caco2bbe (C2) cells. The
      expression of hsp72 in these cells was specifically inhibited by hsp72 antisense
      transfection. The loss of hsp72 expression did not affect growth rate, contact
      inhibition, morphological development, or functional differentiation. In
      contrast, these cells were significantly more sensitive to the injurious effects
      of oxidants and tumor necrosis factor (TNF) but not doxorubicin. To investigate
      potential mechanisms of action, a number of steps in the TNF-mediated cell death
      was measured. Antisense reduction of hsp72 did not alter activation of IkappaB.
      In contrast, mitochondrial cytochrome c release and activation of caspase 9 were
      significantly delayed in hsp72 antisense cells stimulated either with TNF or
      monochloramine. In conclusion, high endogenous expression of hsp72 by intestinal
      adenocarcinoma cells appears to confer selective survival advantage but does not
      affect their growth and differentiation.

PMID- 11504708
TI  - Expression and localization of the CDC34 ubiquitin-conjugating enzyme in
      pediatric acute lymphoblastic leukemia.
AB  - Ubiquitin-dependent protein degradation impacts many cellular processes.However,
      the regulation of ubiquitin-conjugating enzymes (UBCs) in cancer is unknown. We
      find that the human CDC34 UBC protein is expressed at a 3-4 fold higher level (P
      < 0.001) in pediatric T cell than in pre-B-cell acute lymphoblastic leukemia
      (ALL) before treatment in two independent patient sets. The level of CDC34 mRNA
      was similar in both types of leukemia. CDC34 expression levels in normal resting
      T cells, B cells and activated T lymphocytes was comparable with pre-B-cell ALL.
      CDC34 protein (but not mRNA) was also increased in T-cell ALL compared with pre-B
      cell ALL cell lines. The difference in expression was not attributable to
      mutation or associated with altered CDC34 stability. Immunohistochemistry and
      cellular fractionation reveals a heterogeneous CDC34 expression pattern including
      cells containing primarily cytoplasmic or nuclear protein. Thus, a feature of
      pediatric T-cell ALL is posttranscriptional up-regulation and heterogeneous
      localization of the human CDC34 UBC.

PMID- 11504709
TI  - Inducible expression of the megakaryocyte-specific gene glycoprotein IX is
      mediated through an Ets binding site and involves upstream activation of
      extracellular signal-regulated kinase.
AB  - Glycoprotein IX is a megakaryocyte-specific gene crucial for adequate and
      functional expression of the Glycoprotein Ib-IX complex. This study used phorbol
      12-myristate 13-acetate (PMA) and thrombopoietin (TPO)-induced differentiation of
      Dami and UT-7 cells, respectively, to investigate the regulation of inducible
      Glycoprotein IX expression during megakaryocyte differentiation. PMA and TPO were
      able to modulate GPIX expression at mRNA and protein levels. Transient
      transfection studies using nested 5'-deletions and mutations of the GPIX promoter
      demonstrated the absolute requirement of an inverted Ets site 5'-ACTTCCT-3' for
      inducible reporter gene expression. The upstream signaling events associated with
      PMA and TPO-inducible expression of GPIX were also investigated. The mitogen
      activated protein kinase (MAPK)/extracellular signal-regulated kinase inhibitor
      PD98059 inhibited both PMA and TPO-inducible reporter activity in a dose
      dependent manner, whereas inhibition of p38/MAPK had no significant effect. The
      protein kinase C inhibitor GF109203X failed to inhibit TPO-activation of the GPIX
      promoter in UT-7 cells. This study demonstrates that inducible expression in
      response to either PMA or TPO is mediated through the Ets site in the proximal
      promoter of GPIX and is dependent upon the upstream activation of
      MAPK/extracellular signal-regulated kinase.

PMID- 11504710
TI  - Interaction of HRC (histidine-rich Ca(2+)-binding protein) and triadin in the
      lumen of sarcoplasmic reticulum.
AB  - HRC (histidine-rich Ca(2+) binding protein) has been identified from skeletal and
      cardiac muscle and shown to bind Ca(2+) with high capacity and low affinity.
      While HRC resides in the lumen of the sarcoplasmic reticulum, the physiological
      function of HRC is largely unknown. In the present study, we have performed co
      immunoprecipitation experiments and show that HRC binds directly to triadin,
      which is an integral membrane protein of the sarcoplasmic reticulum. Using a
      fusion protein binding assay, we further identified the histidine-rich acidic
      repeats of HRC as responsible for the binding of HRC to triadin. These motifs may
      represent a novel protein-protein interaction domain. The HRC binding domain of
      triadin was also localized by fusion protein binding assay to the lumenal region
      containing the KEKE motif that was previously shown to be involved in the binding
      of triadin to calsequestrin. Notably, the interaction of HRC and triadin is
      Ca(2+)-sensitive. Our data suggest that HRC may play a role in the regulation of
      Ca(2+) release from the sarcoplasmic reticulum by interaction with triadin.

PMID- 11504711
TI  - Increased rates of fatty acid uptake and plasmalemmal fatty acid transporters in
      obese Zucker rats.
AB  - Giant vesicles were used to study the rates of uptake of long-chain fatty acids
      by heart, skeletal muscle, and adipose tissue of obese and lean Zucker rats. With
      obesity there was an increase in vesicular fatty acid uptake of 1.8-fold in
      heart, muscle and adipose tissue. In some tissues only fatty acid translocase
      (FAT) mRNA (heart, +37%; adipose, +80%) and fatty acid-binding protein (FABPpm)
      mRNA (heart, +148%; adipose, +196%) were increased. At the protein level FABPpm
      expression was not changed in any tissues except muscle (+14%), and FAT/CD36
      protein content was altered slightly in adipose tissue (+26%). In marked
      contrast, the plasma membrane FAT/CD36 protein was increased in heart (+60%),
      muscle (+80%), and adipose tissue (+50%). The plasma membrane FABPpm was altered
      only in heart (+50%) and adipose tissues (+70%). Thus, in obesity, alterations in
      fatty acid transport in metabolically important tissues are not associated with
      changes in fatty acid transporter mRNAs or altered fatty acid transport protein
      expression but with their increased abundance at the plasma membrane. We
      speculate that in obesity fatty acid transporters are relocated from an
      intracellular pool to the plasma membrane in heart, muscle, and adipose tissues.

PMID- 11504712
TI  - Chromosome targeting at short polypurine sites by cationic triplex-forming
      oligonucleotides.
AB  - Triplex-forming oligonucleotides (TFOs) bind specifically to duplex DNA and
      provide a strategy for site-directed modification of genomic DNA. Recently we
      demonstrated TFO-mediated targeted gene knockout following systemic
      administration in animals. However, a limitation to this approach is the
      requirement for a polypurine tract (typically 15-30 base pairs (bp)) in the
      target DNA to afford high affinity third strand binding, thus restricting the
      number of sites available for effective targeting. To overcome this limitation,
      we have investigated the ability of chemically modified TFOs to target a short
      (10 bp) site in a chromosomal locus in mouse cells and induce site-specific
      mutations. We report that replacement of the phosphodiester backbone with
      cationic phosphoramidate linkages, either N,N-diethylethylenediamine or N,N
      dimethylaminopropylamine, in a 10-nucleotide, psoralen-conjugated TFO confers
      substantial increases in binding affinity in vitro and is required to achieve
      targeted modification of a chromosomal reporter gene in mammalian cells. The
      triplex-directed, site-specific induction of mutagenesis in the chromosomal
      target was charge- and modification-dependent, with the activity of N,N
      diethylethylenediamine > N,N-dimethylaminopropylamine phosphodiester, resulting
      in 10-, 6-, and <2-fold induction of target gene mutagenesis, respectively.
      Similarly, N,N-diethylethylenediamine and N,N-dimethylaminopropylamine TFOs were
      found to enhance targeting at a 16-bp G:C bp-rich target site in a chromatinized
      episomal target in monkey COS cells, although this longer site was also
      targetable by a phosphodiester TFO. These results indicate that replacement of
      phosphodiester bonds with positively charged N,N-diethylethylenediamine linkages
      enhances intracellular activity and allows targeting of relatively short
      polypurine sites, thereby substantially expanding the number of potential triplex
      target sites in the genome.

PMID- 11504713
TI  - The collagen-like region of surfactant protein A (SP-A) is required for
      correction of surfactant structural and functional defects in the SP-A null
      mouse.
AB  - Pulmonary surfactant isolated from gene-targeted surfactant protein A null mice
      (SP-A(-/-)) is deficient in the surfactant aggregate tubular myelin and has
      surface tension-lowering activity that is easily inhibited by serum proteins in
      vitro. To further elucidate the role of SP-A and its collagen-like region in
      surfactant function, we used the human SP-C promoter to drive expression of rat
      SP-A (rSPA) or SP-A containing a deletion of the collagen-like domain (DeltaG8
      P80) in the Clara cells and alveolar type II cells of SP-A(-/-) mice. The level
      of the SP-A in the alveolar wash of the SP-A(-/-,rSP-A) and SP-A(-/-,DeltaG8-P80)
      mice was 6.1-and 1.3-fold higher, respectively, than in the wild type controls.
      Tissue levels of saturated phosphatidylcholine were slightly reduced in the SP-A(
      /-,rSP-A) mice compared with SP-A(-/-) littermates. Tubular myelin was present in
      the large surfactant aggregates isolated from the SP-A(-/-,rSP-A) lines but not
      in the SP-A(-/-,DeltaG8-P80) mice or SP-A(-/-) controls. The equilibrium and
      minimum surface tensions of surfactant from the SP-A(-/-,rSP-A) mice were similar
      to SP-A(-/-) controls, but both were markedly elevated in the SP-A(-/-,DeltaG8
      P80) mice. There was no defect in the surface tension-lowering activity of
      surfactant from SP-A(+/+,DeltaG8-P80) mice, indicating that the inhibitory effect
      of DeltaG8-P80 on surface activity can be overcome by wild type levels of mouse
      SP-A. The surface activity of surfactant isolated from the SP-A(-/-,rSP-A) but
      not the SP-A(-/-,DeltaG8-P80) mice was more resistant than SP-A(-/-) littermate
      control animals to inhibition by serum proteins in vitro. Pressure volume
      relationships of lungs from the SP-A(-/-), SP-A(-/-,rSP-A), and SP-A(-/-,DeltaG8
      P80) lines were very similar. These data indicate that expression of SP-A in the
      pulmonary epithelium of SP-A(-/-) animals restores tubular myelin formation and
      resistance of isolated surfactant to protein inhibition by a mechanism that is
      dependent on the collagen-like region.

PMID- 11504714
TI  - Structure of a neutral glycosphingolipid recognized by human antibodies in
      polyagglutinable erythrocytes from the rare NOR phenotype.
AB  - NOR is a rare inheritable polyagglutination phenomenon that has been described in
      two families. Our recent studies on these erythrocytes showed they contained at
      least two unique neutral glycosphingolipids, and based on their reactivity with
      Griffonia simplicifolia IB4 (GSL-IB4) isolectin (Kusnierz-Alejska, G., Duk, M.,
      Storry, J. R., Reid, M. E., Wiecek, B., Seyfried, H., and Lisowska, E. (1999)
      Transfusion 39, 32-38), both oligosaccharide chains terminated with an alpha
      galactose residue. The reactivity with GSL-IB4 suggested that these
      oligosaccharide chains terminated with a Galalpha1-->3Gal- sequence and that anti
      NOR agglutinins were common human anti-Galalpha1-->3Gal xenoantibodies. In this
      report we describe the structure of one NOR component (NOR1) that migrated on
      thin-layer chromatographic plates in the region of pentaglycosylceramides.
      Treatment of this sample with alpha-galactosidase and beta-N-acetylhexosaminidase
      was followed by high-performance thin-layer chromatography with product detection
      by lectins and the anti-Gb4 monoclonal antibody. The results suggested that NOR1
      was an alpha-galactosylated Gb4Cer with a beta-N-acetylhexosaminidase-resistant
      GalNAc residue. Gas phase disassembly by ion trap mass spectrometry analysis
      showed the sequence to be Hex1-->4HexN1-->3Hex1-->4Hex1-->4Hex linked to a
      ceramide composed of C18 sphingosine and a C24 monounsaturated fatty acid.
      Together these data indicate NOR1 to be a novel Galalpha1-->4GalNAcbeta1-
      >3Galalpha1-->4Galbeta1-->4 Glc-Cer structure. Additionally it has been shown
      that NOR glycolipids are recognized by human antibodies that were distinct from
      the known anti-Galalpha1-->3Gal xenoantibodies.

PMID- 11504715
TI  - Noncovalent interaction between ubiquitin and the human DNA repair protein Mms2
      is required for Ubc13-mediated polyubiquitination.
AB  - Ubiquitin-conjugating enzyme variants share significant sequence similarity with
      typical E2 (ubiquitin-conjugating) enzymes of the protein ubiquitination pathway
      but lack their characteristic active site cysteine residue. The MMS2 gene of
      Saccharomyces cerevisiae encodes one such ubiquitin-conjugating enzyme variant
      that is involved in the error-free DNA postreplicative repair pathway through its
      association with Ubc13, an E2. The Mms2-Ubc13 heterodimer is capable of linking
      ubiquitin molecules to one another through an isopeptide bond between the C
      terminus and Lys-63. Using highly purified components, we show here that the
      human forms of Mms2 and Ubc13 associate into a heterodimer that is stable over a
      range of conditions. The ubiquitin-thiol ester form of the heterodimer can be
      produced by the direct activation of its Ubc13 subunit with E1 (ubiquitin
      activating enzyme) or by the association of Mms2 with the Ubc13-ubiquitin thiol
      ester. The activated heterodimer is capable of transferring its covalently bound
      ubiquitin to Lys-63 of an untethered ubiquitin molecule, resulting in diubiquitin
      as the predominant species. In (1)H (15)N HSQC ((1)H (15)N heteronuclear single
      quantum coherence) NMR experiments, we have mapped the surface determinants of
      tethered and untethered ubiquitin that interact with Mms2 and Ubc13 in both their
      monomeric and dimeric forms. These results have identified a surface of
      untethered ubiquitin that interacts with Mms2 in the monomeric and heterodimeric
      form. Furthermore, the C-terminal tail of ubiquitin does not participate in this
      interaction. These results suggest that the role of Mms2 is to correctly orient
      either a target-bound or untethered ubiquitin molecule such that its Lys-63 is
      placed proximally to the C terminus of the ubiquitin molecule that is linked to
      the active site of Ubc13.

PMID- 11504716
TI  - Cyclin A-dependent phosphorylation of the ETS-related protein, MEF, restricts its
      activity to the G1 phase of the cell cycle.
AB  - MEF, a recently identified member of the E74 family of ETS-related transcription
      factors, is a strong transcriptional activator of cytokine gene expression. Using
      a green fluorescent protein gene reporter plasmid regulated by an MEF-responsive
      promoter, we determined that the transcriptional activity of MEF is largely
      restricted to the G1 phase of the cell cycle. MEF-dependent transcription was
      suppressed by the expression of cyclin A but not by cyclin D or cyclin E. This
      effect was due to the kinase activity generated by cyclin A expression, as co
      expression of the cyclin-dependent kinase inhibitors p21 or p27, or a dominant
      negative form of CDK2 (DNK2), abrogated the reduction of MEF transcriptional
      activity by cyclin A. Cyclin A-CDK2 phosphorylated MEF protein in vitro more
      efficiently than cyclin D-CDK4 or cyclin E-CDK2, and phosphorylation of MEF by
      cyclin A-CDK2 reduced its ability to bind DNA. We determined one site of
      phosphorylation by cyclin A-CDK2 at the C terminus of MEF, using mass
      spectrometry; mutation of three serine or threonine residues in this region
      significantly reduced phosphorylation of MEF by cyclin A and reduced cyclin A
      mediated suppression of its transactivating activity. These amino acid
      substitutions also reduced the restriction of MEF activity to G1. Phosphorylation
      of MEF by the cyclin A-CDK2 complex controls its transcriptional activity during
      the cell cycle, establishing a novel link between the ETS family of proteins and
      the cell cycle machinery.

PMID- 11504717
TI  - p53 represses androgen-induced transactivation of prostate-specific antigen by
      disrupting hAR amino- to carboxyl-terminal interaction.
AB  - Prostate-specific antigen (PSA) is highly overexpressed in prostate cancer. One
      important regulator of PSA expression is the androgen receptor (AR), the nuclear
      receptor that mediates the biological actions of androgens. AR is able to up
      regulate PSA expression by directly binding and activating the promoter of this
      gene. We provide evidence here that that this AR activity is repressed by the
      tumor suppressor protein p53. p53 appears to exert its inhibition of human AR
      (hAR) by disrupting its amino- to carboxyl-terminal (N-to-C) interaction, which
      is thought to be responsible for the homodimerization of this receptor.
      Consistent with this, p53 is also able to block hAR DNA binding in vitro. Our
      previous data have shown that c-Jun can mediate hAR transactivation, and this
      appears to result from a positive effect on hAR N-to-C interaction and DNA
      binding. Interestingly, c-Jun is able to relieve the negative effects of p53 on
      hAR transactivation, N-to-C interaction, and DNA binding, demonstrating
      antagonistic activities of these two proteins. Importantly, a p53 mutation found
      in metastatic prostate cancer severely disrupts the p53 negative activity on hAR,
      suggesting that the inability of p53 mutants to down-regulate hAR is, in part,
      responsible for the metastatic phenotype.

PMID- 11504718
TI  - Identification of a spectrally stable proteolytic fragment of human neutrophil
      flavocytochrome b composed of the NH2-terminal regions of gp91(phox) and
      p22(phox).
AB  - A heme-bearing polypeptide core of human neutrophil flavocytochrome b(558) was
      isolated by applying high performance, size exclusion, liquid chromatography to
      partially purified Triton X-100-solubilized flavocytochrome b that had been
      exposed to endoproteinase Glu-C for 1 h. The fragment was composed of two
      polypeptides of 60-66 and 17 kDa by SDS-polyacrylamide gel electrophoresis and
      retained a native heme absorbance spectrum that was stable for several days when
      stored at 4 degrees C in detergent-containing buffer. These properties suggested
      that the majority of the flavocytochrome b heme environment remained intact.
      Continued digestion up to 4.5 h yielded several heme-associated fragments that
      were variable in composition between experiments. Digestion beyond 4.5 h resulted
      in a gradual loss of recoverable heme. N-Linked deglycosylation and reduction and
      alkylation of the 1-h digestion fragment did not affect the electrophoretic
      mobility of the 17-kDa fragment but reduced the 60-66-kDa fragment to 39 kDa.
      Sequence and immunoblot analyses identified the fragments as the NH(2)-terminal
      320-363 amino acid residues of gp91(phox) and the NH(2)-terminal 169-171 amino
      acid residues of p22(phox). These findings provide direct evidence that the
      primarily hydrophobic NH(2)-terminal regions of flavocytochrome b are responsible
      for heme ligation.

PMID- 11504719
TI  - Timely release of both replication forks from oriC requires modulation of origin
      topology.
AB  - Initiation of DNA replication at oriC occurs bidirectionally both in vivo and in
      vitro. Although the proteins involved in establishing the replication forks are
      known, little is known about the events that ensure that initiation is
      bidirectional. We show here that in the absence of DNA gyrase, replication fork
      progression from oriC on a plasmid template in vitro is unidirectional, although
      both replication forks have formed at the origin. There was no bias in the
      release of one fork or the other, ruling out protein blockage of one fork as a
      possible reason for the asymmetric release. Timely release of both forks required
      the presence of either DNA gyrase or topoisomerase IV, suggesting that modulation
      of the topology of the origin region is the governing factor.

PMID- 11504720
TI  - Visualization of in vivo direct interaction between HIV-1 TAT and human cyclin T1
      in specific subcellular compartments by fluorescence resonance energy transfer.
AB  - Human cyclin T1, a component of the P-TEFb kinase complex, was originally
      identified through its biochemical interaction with the Tat transactivator
      protein of human immunodeficiency virus type 1 (HIV-1). Current understanding
      suggests that binding of Tat to P-TEFb is required to promote efficient
      transcriptional elongation of viral RNAs. However, the dynamics and the
      subnuclear localization of this process are still largely unexplored in vivo.
      Here we exploit high resolution fluorescence resonance energy transfer (FRET) to
      visualize and quantitatively analyze the direct interaction between Tat and
      cyclin T1 inside the cells. We observed that cyclin T1 resides in specific
      subnuclear foci which are in close contact with nuclear speckles and that Tat
      determines its redistribution outside of these compartments. Consistent with this
      observation, strong FRET was observed between the two proteins both in the
      cytoplasm and in regions of the nucleus outside of cyclin T1 foci and overlapping
      with Tat localization. These results are consistent with a model by which Tat
      recruits cyclin T1 outside of the nuclear compartments where the protein resides
      to promote transcriptional activation.

PMID- 11504721
TI  - Building a replisome solution structure by elucidation of protein-protein
      interactions in the bacteriophage T4 DNA polymerase holoenzyme.
AB  - Assembly of DNA replication systems requires the coordinated actions of many
      proteins. The multiprotein complexes formed as intermediates on the pathway to
      the final DNA polymerase holoenzyme have been shown to have distinct structures
      relative to the ground-state structures of the individual proteins. By using a
      variety of solution-phase techniques, we have elucidated additional information
      about the solution structure of the bacteriophage T4 holoenzyme. Photocross
      linking and mass spectrometry were used to demonstrate interactions between I107C
      of the sliding clamp and the DNA polymerase. Fluorescence resonance energy
      transfer, analytical ultracentrifugation, and isothermal titration calorimetry
      measurements were used to demonstrate that the C terminus of the DNA polymerase
      can interact at two distinct locations on the sliding clamp. Both of these
      binding modes may be used during holoenzyme assembly, but only one of these
      binding modes is found in the final holoenzyme. Present and previous solution
      interaction data were used to build a model of the holoenzyme that is consistent
      with these data.

PMID- 11504722
TI  - Endocytosis is enhanced in Tangier fibroblasts: possible role of ATP-binding
      cassette protein A1 in endosomal vesicular transport.
AB  - A human genetic disorder, Tangier disease, has been linked recently to mutations
      in ATP-binding cassette protein A1 (ABCA1). In addition to its function in
      apoprotein A-I-mediated lipid removal, ABCA1 was also shown to be a
      phosphatidylserine (PS) translocase that facilitates PS exofacial flipping. This
      PS translocation is crucial for the plasma membrane to produce protrusions
      enabling the engulfment of apoptotic cells. In this report, we show that ABCA1
      also plays a role in endocytosis. Receptor-mediated endocytosis, probed by both
      transferrin and low density lipoprotein, is up-regulated by more than 50% in
      homozygous Tangier fibroblasts in comparison with controls. Fluid-phase uptake is
      increased similarly. We also demonstrate that bulk membrane flow, including lipid
      endocytosis and exocytosis, is accelerated greatly in Tangier cells. Moreover,
      endocytosis is similarly enhanced in normal fibroblasts when ABCA1 function is
      inhibited by glyburide, whereas glyburide has no effect on endocytosis in Tangier
      cells. In addition, we demonstrate a decreased annexin V binding in Tangier
      fibroblasts as compared with controls, supporting the notion that PS
      transmembrane distribution is indeed defective in the presence of ABCA1
      mutations. Furthermore, adding a PS analog to the exofacial leaflet of the plasma
      membrane normalizes endocytosis in Tangier cells. Taken together, these data
      demonstrate that ABCA1 plays an important role in endocytosis. We speculate that
      this is related to the PS translocase function of ABCA1. A loss of functional
      ABCA1, as in the case of Tangier cells, enhances membrane inward bending and
      facilitates endocytosis.

PMID- 11504723
TI  - Vezf1/DB1 is an endothelial cell-specific transcription factor that regulates
      expression of the endothelin-1 promoter.
AB  - Coordinated gene regulation within the vascular endothelium is required for
      normal cardiovascular patterning during development and for vascular homeostasis
      during adulthood, yet little is known about the mechanisms that regulate
      endothelial transcriptional events. Vascular endothelial zinc finger 1
      (Vezf1)/DB1 is a recently identified zinc finger-containing protein that is
      expressed specifically within endothelial cells during development. In this
      report, we demonstrate that Vezf1/DB1 is a nuclear localizing protein that
      potently and specifically activates transcription mediated by the human
      endothelin-1 promoter, in a Tax-independent manner, in transient transfection
      assays. Using a combination of deletion mutagenesis and electrophoretic mobility
      shift assays, a novel Vezf1/DB1-responsive element was localized to a 6-base pair
      (bp) motif, ACCCCC, located 47 bp upstream of the endothelin-1 transcription
      start site. Recombinant Vezf1/DB1 also bound to this sequence, and a 2-bp
      mutation in this element abolished Vezf1/DB1 responsiveness by the endothelin-1
      promoter. Vezf1/DB1 could be identified with a specific antibody in nuclear
      complexes from endothelial cells that bound to this element. Regulation of
      endothelin-1 promoter activity by Vezf1/DB1 provides a mechanism for endothelin-1
      expression in the vascular endothelium during development and to maintain
      vascular tone; Vezf1/DB1 itself is a candidate transcription factor for modifying
      endothelial cell phenotypes in order to appropriately assemble and maintain the
      cardiovascular system.

PMID- 11504724
TI  - Redistribution of BRCA1 among four different protein complexes following
      replication blockage.
AB  - The BRCA1 protein is known to participate in multiple cellular processes. In
      these experiments, we resolved four distinct BRCA1-containing complexes. We found
      BRCA1 associated with the RNA polymerase II holoenzyme (holo-pol), a large mass
      complex called the fraction 5 complex, the Rad50-Mre11-Nbs1 complex, and a
      complex that has not been described previously. We observed this new complex
      after treating cells with hydroxyurea, suggesting that the hydroxyurea-induced
      complex (HUIC) is involved with the response to DNA replication blockage. After
      hydroxyurea treatment of cells, BRCA1 content decreased in the holo-pol and the
      fraction 5 complex, and BRCA1 was redistributed to the HUIC. The HUIC was shown
      not to contain a number of holo-pol components or the Rad50-Mre11-Nbs1 complex
      but was associated with the BRCA1-associated RING domain protein BARD1. These
      data suggest that BRCA1 participates in multiple cellular processes by multiple
      protein complexes and that the BRCA1 content of these complexes is dynamically
      altered after DNA replication blockage.

PMID- 11504725
TI  - The fidelity of human DNA polymerase gamma with and without exonucleolytic
      proofreading and the p55 accessory subunit.
AB  - Mutations in human mitochondrial DNA influence aging, induce severe neuromuscular
      pathologies, cause maternally inherited metabolic diseases, and suppress
      apoptosis. Since the genetic stability of mitochondrial DNA depends on the
      accuracy of DNA polymerase gamma (pol gamma), we investigated the fidelity of DNA
      synthesis by human pol gamma. Comparison of the wild-type 140-kDa catalytic
      subunit to its exonuclease-deficient derivative indicates pol gamma has high base
      substitution fidelity that results from high nucleotide selectivity and
      exonucleolytic proofreading. pol gamma is also relatively accurate for single
      base additions and deletions in non-iterated and short repetitive sequences.
      However, when copying homopolymeric sequences longer than four nucleotides, pol
      gamma has low frameshift fidelity and also generates base substitutions inferred
      to result from a primer dislocation mechanism. The ability of pol gamma both to
      make and to proofread dislocation intermediates is the first such evidence for a
      family A polymerase. Including the p55 accessory subunit, which confers
      processivity to the pol gamma catalytic subunit, decreases frameshift and base
      substitution fidelity. Kinetic analyses indicate that p55 promotes extension of
      mismatched termini to lower the fidelity. These data suggest that homopolymeric
      runs in mitochondrial DNA may be particularly prone to frameshift mutation in
      vivo due to replication errors by pol gamma.

PMID- 11504726
TI  - Presenilin 1 regulates beta-catenin-mediated transcription in a glycogen synthase
      kinase-3-independent fashion.
AB  - Presenilin 1 (PS1) is linked with Alzheimer's disease but exhibits functional
      roles regulating growth and development. For instance, PS1 binds to beta-catenin
      and modulates beta-catenin signaling. In the current study, we observed that
      knockout of PS1 inhibited beta-catenin-mediated transcription by 35%, as shown by
      a luciferase reporter driven by the hTcf-4 promoter. Overexpressing wild-type PS1
      increased beta-catenin-mediated transcription by 37.5%, and overexpressing PS1
      with mutations associated with Alzheimer's disease decreased beta-catenin
      mediated transcription by 66%. To examine whether regulation of beta-catenin by
      PS1 requires phosphorylation by glycogen synthase kinase 3beta (GSK 3beta), we
      examined whether inhibiting GSK 3beta activity overcomes the inhibition of beta
      catenin transcription induced by mutant PS1 constructs. Cells expressing wild
      type or mutant PS1 were treated with LiCl, which inhibits GSK 3beta, or
      transfected with beta-catenin constructs that lack the GSK 3beta phosphorylation
      sites. Neither treatment overcame PS1-mediated inhibition of beta-catenin
      signaling, suggesting that regulation of beta-catenin by PS1 was not affected by
      the activity of GSK 3beta. To investigate how PS1 might regulate beta-catenin
      signaling, we determined whether PS1 interacts with other elements of the beta
      catenin signaling cascade, such as the Tcf-4 transcription factor.
      Coimmunoprecipitation studies showed binding of PS1 and hTcf-4, and examining
      nuclear isolates indicated that nuclear hTcf-4 was decreased in cells expressing
      mutant PS1. These data show that PS1 interacts with multiple components of the
      beta-catenin signaling cascade and suggest that PS1 regulates beta-catenin in a
      manner independent of GSK 3beta activity.

PMID- 11504727
TI  - Functional equality in the absence of structural similarity: an added dimension
      to molecular mimicry.
AB  - The crystal structure of meso-tetrasulfonatophenylporphyrin complexed with
      concanavalin A (ConA) was determined at 1.9 A resolution. Comparison of this
      structure with that of ConA bound to methyl alpha-d-mannopyranoside provided
      direct structural evidence of molecular mimicry in the context of ligand receptor
      binding. The sulfonatophenyl group of meso-tetrasulfonatophenylporphyrin occupies
      the same binding site on ConA as that of methyl alpha-d-mannopyranoside, a
      natural ligand. A pair of stacked porphyrin molecules stabilizes the crystal
      structure by end-to-end cross-linking with ConA resulting in a network similar to
      that observed upon agglutination of cells by lectins. The porphyrin binds to ConA
      predominantly through hydrogen bonds and water-mediated interactions. The
      sandwiched water molecules in the complex play a cementing role, facilitating
      favorable binding of porphyrin. Seven of the eight hydrogen bonds observed
      between methyl alpha-d-mannopyranoside and ConA are mimicked by the
      sulfonatophenyl group of porphyrin after incorporating two water molecules. Thus,
      the similarity in chemical interactions was manifested in terms of functional
      mimicry despite the obvious structural dissimilarity between the sugar and the
      porphyrin.

PMID- 11504728
TI  - The CWH8 gene encodes a dolichyl pyrophosphate phosphatase with a luminally
      oriented active site in the endoplasmic reticulum of Saccharomyces cerevisiae.
AB  - Mutations in the CWH8 gene, which encodes an ER transmembrane protein with a
      phosphate binding pocket in Saccharomyces cerevisiae, result in a deficiency in
      dolichyl pyrophosphate (Dol-P-P)-linked oligosaccharide intermediate synthesis
      and protein N-glycosylation (van Berkel, M. A., Rieger, M., te Heesen, S., Ram,
      A. F., van den Ende, H., Aebi, M., and Klis, F. M. (1999) Glycobiology 9, 243
      253). Genetic, enzymological, and topological approaches were taken to
      investigate the potential role of Cwh8p in Dol-P-P/Dol-P metabolism.
      Overexpression of Cwh8p in the yeast double mutant strain, lacking LPP1/DPP1,
      resulted in an impressive increase in Dol-P-P phosphatase activity, a relatively
      small increase in Dol-P phosphatase activity, but no change in phosphatidate (PA)
      phosphatase activity in microsomal fractions. The Dol-P-P phosphatase encoded by
      CWH8 is optimally active in the presence of 0.5% octyl glucoside and relatively
      unstable in Triton X-100, distinguishing this activity from the lipid
      phosphatases encoded by LPP1 and DPP1. Stoichiometric amounts of P(i) and Dol-P
      are formed during the enzymatic reaction indicating that Cwh8p cleaves the
      anhydride linkage in Dol-P-P. Membrane fractions from Sf-9 cells expressing Cwh8p
      contained a 30-fold higher level of Dol-P-P phosphatase activity, a slight
      increase in Dol-P phosphatase activity, but no increase in PA phosphatase
      relative to controls. This is the first report of a lipid phosphatase that
      hydrolyzes Dol-P-P/Dol-P but not PA. In accord with this enzymatic function, Dol
      P-P accumulated in cells lacking the Dol-P-P phosphatase. Topological studies
      using different approaches indicate that Cwh8p is a transmembrane protein with a
      luminally oriented active site. The specificity, subcellular location, and
      topological orientation of this novel enzyme are consistent with a role in the re
      utilization of the glycosyl carrier lipid for additional rounds of lipid
      intermediate biosynthesis after its release during protein N-glycosylation
      reactions.

PMID- 11504729
TI  - DNA pairing and strand exchange by the Escherichia coli RecA and yeast Rad51
      proteins without ATP hydrolysis: on the importance of not getting stuck.
AB  - The bacterial RecA protein and the homologous Rad51 protein in eukaryotes both
      bind to single-stranded DNA (ssDNA), align it with a homologous duplex, and
      promote an extensive strand exchange between them. Both reactions have
      properties, including a tolerance of base analog substitutions that tend to
      eliminate major groove hydrogen bonding potential, that suggest a common
      molecular process underlies the DNA strand exchange promoted by RecA and Rad51.
      However, optimal conditions for the DNA pairing and DNA strand exchange reactions
      promoted by the RecA and Rad51 proteins in vitro are substantially different.
      When conditions are optimized independently for both proteins, RecA promotes DNA
      pairing reactions with short oligonucleotides at a faster rate than Rad51. For
      both proteins, conditions that improve DNA pairing can inhibit extensive DNA
      strand exchange reactions in the absence of ATP hydrolysis. Extensive strand
      exchange requires a spooling of duplex DNA into a recombinase-ssDNA complex, a
      process that can be halted by any interaction elsewhere on the same duplex that
      restricts free rotation of the duplex and/or complex, I.e. the reaction can get
      stuck. Optimization of an extensive DNA strand exchange without ATP hydrolysis
      requires conditions that decrease nonproductive interactions of recombinase-ssDNA
      complexes with the duplex DNA substrate.

PMID- 11504730
TI  - 27-hydroxycholesterol is an endogenous ligand for liver X receptor in cholesterol
      loaded cells.
AB  - The nuclear receptors liver X receptor alpha (LXRalpha) (NR1H3) and LXRbeta
      (NR1H2) are important regulators of genes involved in lipid metabolism, including
      ABCA1, ABCG1, and sterol regulatory element-binding protein-1c (SREBP-1c).
      Although it has been demonstrated that oxysterols are LXR ligands, little is
      known about the identity of the physiological activators of these receptors. Here
      we confirm earlier studies demonstrating a dose-dependent induction of ABCA1 and
      ABCG1 in human monocyte-derived macrophages by cholesterol loading. In addition,
      we show that formation of 27-hydroxycholesterol and cholestenoic acid, products
      of CYP27 action on cholesterol, is dependent on the dose of cholesterol used to
      load the cells. Other proposed LXR ligands, including 20(S)-hydroxycholesterol,
      22(R)-hydroxycholesterol, and 24(S),25-epoxycholesterol, could not be detected
      under these conditions. A role for CYP27 in regulation of cholesterol-induced
      genes was demonstrated by the following findings. 1) Introduction of CYP27 into
      HEK-293 cells conferred an induction of ABCG1 and SREBP-1c; 2) upon cholesterol
      loading, CYP27-expressing cells induce these genes to a greater extent than in
      control cells; 3) in CYP27-deficient human skin fibroblasts, the induction of
      ABCA1 in response to cholesterol loading was ablated; and 4) in a coactivator
      association assay, 27-hydroxycholesterol functionally activated LXR. We conclude
      that 27-hydroxylation of cholesterol is an important pathway for LXR activation
      in response to cholesterol overload.

PMID- 11504731
TI  - Erythropoietin receptor-mediated inhibition of exocytotic glutamate release
      confers neuroprotection during chemical ischemia.
AB  - Erythropoietin (EPO) reduced Ca(2+)-induced glutamate (Glu) release from cultured
      cerebellar granule neurons. Inhibition was also produced by EPO mimetic peptide 1
      (EMP1), a small synthetic peptide agonist of EPO receptor (EPO-R), but not by
      iEMP1, an inactive analogue of EMP1. EPO and EMP1 induced autophosphorylation of
      Janus kinase 2 (JAK2), a tyrosine kinase that associates with EPO-R. Furthermore,
      genistein, but not genistin, antagonized both the phosphorylation of JAK2 and the
      suppression of Glu release induced by EPO and EMP1. During chemical ischemia,
      substantial amounts of Glu were released from cultured cerebellar and hippocampal
      neurons by at least two distinct mechanisms. In the early phase, Glu release
      occurred by exocytosis of synaptic vesicle contents, because it was abolished by
      botulinum type B neurotoxin (BoNT/B). In contrast, the later phase of Glu release
      mainly involved a BoNT/B-insensitive non-exocytotic pathway. EMP1 inhibited Glu
      release only during the early exocytotic phase. A 20-min exposure of hippocampal
      slices to chemical ischemia induced neuronal cell death, especially in the CA1
      region and the dentate gyrus, which was suppressed by EMP1 but not iEMP1.
      However, EMP1 did not attenuate neuronal cell death induced by exogenously
      applied Glu. These results suggest that activation of EPO-R suppresses ischemic
      cell death by inhibiting the exocytosis of Glu.

PMID- 11504732
TI  - Identification and characterization of mammalian mitochondrial tRNA
      nucleotidyltransferases.
AB  - The CCA-adding enzyme (ATP:tRNA adenylyltransferase or CTP:tRNA
      cytidylyltransferase (EC )) generates the conserved CCA sequence responsible for
      the attachment of amino acid at the 3' terminus of tRNA molecules. It was shown
      that enzymes from various organisms strictly recognize the elbow region of tRNA
      formed by the conserved D- and T-loops. However, most of the mammalian
      mitochondrial (mt) tRNAs lack consensus sequences in both D- and T-loops. To
      characterize the mammalian mt CCA-adding enzymes, we have partially purified the
      enzyme from bovine liver mitochondria and determined cDNA sequences from human
      and mouse dbESTs by mass spectrometric analysis. The identified sequences
      contained typical amino-terminal peptides for mitochondrial protein import and
      had characteristics of the class II nucleotidyltransferase superfamily that
      includes eukaryotic and eubacterial CCA-adding enzymes. The human recombinant
      enzyme was overexpressed in Escherichia coli, and its CCA-adding activity was
      characterized using several mt tRNAs as substrates. The results clearly show that
      the human mt CCA-adding enzyme can efficiently repair mt tRNAs that are poor
      substrates for the E. coli enzyme although both enzymes work equally well on
      cytoplasmic tRNAs. This suggests that the mammalian mt enzymes have evolved so as
      to recognize mt tRNAs with unusual structures.

PMID- 11504733
TI  - Characterization of the signal peptide processing and membrane association of
      human cytomegalovirus glycoprotein O.
AB  - Human cytomegalovirus (HCMV) has a structurally complex envelope that contains
      multiple glycoproteins. These glycoproteins are involved in virus entry, virus
      maturation, and cell-cell spread of infection. Glycoprotein H (gH), glycoprotein
      L (gL), and glycoprotein O (gO) associate covalently to form a unique disulfide
      bonded tripartite complex. Glycoprotein O was recently discovered, and its basic
      structure, as well as that of the tripartite complex, remains uncharacterized.
      Based on hydropathy analysis, we hypothesized that gO could adopt a type II
      transmembrane orientation. The data presented here, however, reveal that the
      single hydrophobic domain of gO functions as a cleavable signal peptide that is
      absent from the mature molecule. Although it lacks a membrane anchor,
      glycoprotein O is associated with the membranes of HCMV-infected cells. The
      sophisticated organization of the gH.gL.gO complex reflects the intricate nature
      of the multicomponent entry and fusion machinery encoded by HCMV.

PMID- 11504734
TI  - Interaction between protein phosphatase 5 and the A subunit of protein
      phosphatase 2A: evidence for a heterotrimeric form of protein phosphatase 5.
AB  - Members of the phosphoprotein phosphatase family of serine/threonine phosphatases
      are thought to exist in different native oligomeric complexes. Protein
      phosphatase 2A (PP2A) is composed of a catalytic subunit (PP2Ac) that complexes
      with an A subunit, which in turn also interacts with one of many B subunits that
      regulate substrate specificity and/or (sub)cellular localization of the enzyme.
      Another family member, protein phosphatase 5 (PP5), contains a tetratricopeptide
      repeat domain at its N terminus, which has been suggested to mediate interactions
      with other proteins. PP5 was not thought to interact with partners homologous to
      the A or B subunits that exist within PP2A. However, our results indicate that
      this may not be the case. A yeast two-hybrid screen revealed an interaction
      between PP5 and the A subunit of PP2A. This interaction was confirmed for
      endogenous proteins in vivo using immunoprecipitation analysis and for
      recombinant proteins by in vitro binding experiments. Our results also indicate
      that the tetratricopeptide repeat domain of PP5 is required and sufficient for
      this interaction. In addition, immunoprecipitated PP5 contains associated B
      subunits. Thus, our results suggest that PP5 can exist in a PP2A-like
      heterotrimeric form containing both A and B subunits.

PMID- 11504735
TI  - The Hemophilus influenzae Hap autotransporter is a chymotrypsin clan serine
      protease and undergoes autoproteolysis via an intermolecular mechanism.
AB  - The Hemophilus influenzae Hap adhesin is an autotransporter protein that
      undergoes an autoproteolytic cleavage event resulting in extracellular release of
      the adhesin domain (Hap(s)) from the membrane-associated translocator domain
      (Hap(beta)). Hap autoproteolysis is mediated by Ser(243) and occurs at LN1036-7
      and to a lesser extent at more COOH-terminal alternate sites. In the present
      study, we sought to further define the mechanism of Hap autoproteolysis. Site
      directed mutagenesis of residues His(98) and Asp(140) identified a catalytic
      triad conserved among a subfamily of autotransporters and reminiscent of the SA
      (chymotrypsin) clan of serine proteases. Amino-terminal amino acid sequencing of
      histidine-tagged Hap(beta) species and site-directed mutagenesis established that
      autoproteolysis occurs at LT1046-7, FA1077-8, and FS1067-8, revealing a consensus
      target sequence for cleavage that consists of ((Q/R)(A/S)X(L/F)) at the P4
      through P1 positions. Examination of a recombinant strain co-expressing a Hap
      derivative lacking all cleavage sites (HapDelta1036-99) and a Hap derivative
      lacking proteolytic activity (HapS243A) demonstrated that autoproteolysis occurs
      by an intermolecular mechanism. Kinetic analysis of Hap autoproteolysis in
      bacteria expressing Hap under control of an inducible promoter demonstrated that
      autoproteolysis increases as the density of Hap precursor in the outer membrane
      increases, confirming intermolecular cleavage and suggesting a novel mechanism
      for regulation of bacterial adherence and microcolony formation.

PMID- 11504736
TI  - Translational repression of the Escherichia coli alpha operon mRNA: importance of
      an mRNA conformational switch and a ternary entrapment complex.
AB  - Ribosomal protein S4 represses synthesis of the four ribosomal proteins
      (including itself) in the Escherichia coli alpha operon by binding to a nested
      pseudoknot structure that spans the ribosome binding site. A model for the
      repression mechanism previously proposed two unusual features: (i) the mRNA
      switches between conformations that are "active" or "inactive" in translation,
      with S4 as an allosteric effector of the inactive form, and (ii) S4 holds the 30
      S subunit in an unproductive complex on the mRNA ("entrapment"), in contrast to
      direct competition between repressor and ribosome binding ("displacement"). These
      two key points have been experimentally tested. First, it is found that the mRNA
      pseudoknot exists in an equilibrium between two conformers with different
      electrophoretic mobilities. S4 selectively binds to one form of the RNA, as
      predicted for an allosteric effector; binding of ribosomal 30 S subunits is
      nearly equal in the two forms. Second, we have used S4 labeled at a unique
      cysteine with either of two fluorophores to characterize its interactions with
      mRNA and 30 S subunits. Equilibrium experiments detect the formation of a
      specific ternary complex of S4, mRNA pseudoknot, and 30 S subunits. The existence
      of this ternary complex is unambiguous evidence for translational repression of
      the alpha operon by an entrapment mechanism.

PMID- 11504737
TI  - Haa1, a protein homologous to the copper-regulated transcription factor Ace1, is
      a novel transcriptional activator.
AB  - The Saccharomyces cerevisiae genome contains a predicted gene, YPR008w,
      homologous to the gene encoding the copper-activated transcription factor Ace1.
      The product of the YPR008w gene, designated Haa1, regulates the transcription of
      a set of yeast genes, many of which encode membrane proteins. Two main target
      genes of Haa1 are the multidrug resistance gene YGR138c and the YRO2 homolog to
      the plasma membrane Hsp30. Haa1 is localized to the nucleus. Haa1-induced
      expression of YGR138c and YRO2 appears to be direct. Induction of HAA1 using a
      GAL1/HAA1 fusion gene resulted in rapid galactose-induced expression of both HAA1
      and target genes. Although Haa1 has a sequence very similar to the Cu-activated
      DNA binding domain of Ace1, expression of Haa1 target genes was found to be
      independent of the copper status of cells. Haa1 does not exhibit
      metalloregulation in cells incubated with a range of transition metal salts. Haa1
      does not exhibit any cross-talk with Ace1. Overexpression of Haa1 does not
      compensate for cells lacking a functional Ace1. The lack of metalloregulation of
      Haa1 despite the strong sequence similarity to the copper regulatory domain of
      Ace1 is discussed.

PMID- 11504738
TI  - EWI-2 is a major CD9 and CD81 partner and member of a novel Ig protein subfamily.
AB  - A novel Ig superfamily protein, EWI-2, was co-purified with tetraspanin protein
      CD81 under relatively stringent Brij 96 detergent conditions and identified by
      mass spectrometric protein sequencing. EWI-2 associated specifically with CD9 and
      CD81 but not with other tetraspanins or with integrins. Immunodepletion
      experiments indicated that EWI-2-CD9/CD81 interactions are highly stoichiometric,
      with approximately 70% of CD9 and CD81 associated with EWI-2 in an embryonic
      kidney cell line. The EWI-2 molecule was covalently cross-linked (in separate
      complexes) to both CD81 and CD9, suggesting that association is direct. EWI-2 is
      part of a novel Ig subfamily that includes EWI-F (F2alpha receptor regulatory
      protein (FPRP), CD9P-1), EWI-3 (IgSF3), and EWI-101 (CD101). All four members of
      this Ig subfamily contain a Glu-Trp-Ile (EWI) motif not seen in other Ig
      proteins. As shown previously, the EWI-F molecule likewise forms highly proximal,
      specific, and stoichiometric complexes with CD9 and CD81. Human and murine EWI-2
      protein sequences are 91% identical, and transcripts in the two species are
      expressed in virtually every tissue tested. Thus, EWI-2 potentially contributes
      to a variety of CD9 and CD81 functions seen in different cell and tissue types.

PMID- 11504739
TI  - A remodeling system of the 3'-sulfo-Lewis a and 3'-sulfo-Lewis x epitopes.
AB  - It has been reported that the chemically synthesized 3'-sulfo-Le(a) and 3'-sulfo
      Le(x) epitopes have a high potential as a ligand for selectins. To elucidate the
      physiological functions of 3'-sulfated Lewis epitopes, a remodeling system was
      developed using a combination of a betaGal-3-O-sulfotransferase GP3ST, hitherto
      known alpha1,3/1,4-fucosyltransferases (FucT-III, IV, V, VI, VII, and IX) and
      arylsulfatase A. The pyridylaminated (PA) lacto-N-tetraose (Galbeta1-3GlcNAcbeta1
      3Galbeta1-4Glc) was first converted to 3'-sulfolacto-N-fucopentaose II (sulfo
      3Galbeta1-3(Fucalpha1-4)GlcNAcbeta1-3Galbeta1-4Glc)-PA by sequential reactions
      with GP3ST and FucT-III. The 3'-sulfolacto-N-fucopentaose III (sulfo-3Galbeta1
      4(Fucalpha1-3)GlcNAcbeta1-3Galbeta1-4Glc)-PA was then synthesized from lacto-N
      neotetraose (Galbeta1-4GlcNAcbeta1-3Galbeta1-4Glc)-PA by GP3ST and FucT-III, -IV,
      -V, -VI, -VII, or -IX in a similar manner. The substrate specificity for the 3'
      sulfated acceptor of the alpha1,3-fucosyltransferases was considerably different
      from that for the non-substituted and 3'-sialylated varieties. When the GP3ST
      gene was introduced into A549 and Chinese hamster ovary cells expressing FucT
      III, they began to express 3'-sulfo-Le(a) and 3'-sulfo-Le(x) epitopes,
      respectively, suggesting that GP3ST is responsible for their biosynthesis in
      vivo. The expression of the 3'-sialyl-Le(x) epitope on Chinese hamster ovary
      cells was attenuated by the introduction of GP3ST gene, indicating that GP3ST and
      alpha2,3-sialyltransferase compete for the common Galbeta1-4GlcNAc-R
      oligosaccharides. Last, arylsulfatase A, which is a lysosomal hydrolase that
      catalyzes the desulfation of 3-O-sulfogalactosyl residues in glycolipids, was
      found to hydrolyze the sulfate ester bond on the 3'-sulfo-Le(x) (type 2 chain)
      but not that on the 3'-sulfo-Le(a) (type 1 chain). The present remodeling system
      might be of potential use as a tool for the study of the physiological roles of
      3'-sulfated Lewis epitopes, including interaction with selectins.

PMID- 11504740
TI  - Thalidomide in the treatment of plasma cell malignancies.

PMID- 11504741
TI  - Treatment of Waldenstrom's macroglobulinemia with thalidomide.
AB  - PURPOSE: We performed a prospective phase II study to assess the activity of
      thalidomide in patients with Waldenstrom's macroglobulinemia (WM). PATIENTS AND
      METHODS: Twenty patients with WM were treated with thalidomide at a starting dose
      of 200 mg daily with dose escalation in 200-mg increments every 14 days as
      tolerated to a maximum of 600 mg. All patients were symptomatic, their median age
      was 74 years, and 10 patients were previously untreated. RESULTS: On an intent-to
      treat basis, five (25%) of 20 patients achieved a partial response after
      treatment. Responses occurred in three of 10 previously untreated and in two of
      10 pretreated patients. None of the patients treated during refractory relapse or
      with disease duration exceeding 2 years responded to thalidomide. Time to
      response was short, ranging between 0.8 months to 2.8 months. Adverse effects
      were common but reversible and consisted primarily of constipation, somnolence,
      fatigue, and mood changes. The daily dose of thalidomide was escalated to 600 mg
      in only five patients (25%), and in seven patients (35%), this agent was
      discontinued within 2 months because of intolerance. CONCLUSION: Our data
      indicate that thalidomide has activity in WM but only low doses were tolerated in
      this elderly patient population. Confirmatory studies as well as studies that
      will combine thalidomide with chemotherapy or with rituximab may be relevant.

PMID- 11504742
TI  - Prognostic factors in primary cutaneous large B-cell lymphomas: a European
      multicenter study.
AB  - PURPOSE: Most primary cutaneous B-cell lymphomas have an excellent prognosis.
      However, primary cutaneous large B-cell lymphomas (PCLBCLs) of the leg have been
      recognized as a distinct entity with a poorer prognosis in the European
      Organization for Research and Treatment of Cancer (EORTC) classification. This
      distinction on the basis of site has been debated. Our aim was to identify
      independent prognostic factors in a large European multicenter series of PCLBCL.
      PATIENTS AND METHODS: The clinical and histologic data of 145 patients with
      PCLBCL were evaluated. According to the EORTC classification, 48 patients had a
      PCLBCL of the leg and 97 had a primary cutaneous follicle center-cell lymphoma
      (PCFCCL). Data from both groups were compared. Univariate and multivariate
      analyses of specific survival were performed using a Cox proportional hazards
      model. RESULTS: Compared with PCFCCL, PCLBCL-leg were characterized by an older
      age of onset, a more recent history of skin lesions, a more frequent predominance
      of tumor cells with round nuclei and positive bcl-2 staining, and a poorer 5-year
      disease-specific survival rate (52% v 94%; P <.0001). Univariate survival
      analysis in the entire study group showed that older age, a more recent onset of
      skin lesions, the location on the leg, multiple skin lesions, and the round-cell
      morphology were significantly related to death. In multivariate analysis, the
      round-cell morphology (P <.0001), the location on the leg (P =.002), and multiple
      skin lesions (P =.01) remained independent prognostic factors. The round-cell
      morphology was an adverse prognostic factor both in PCLBCL-leg and in PCFCCL,
      whereas multiple skin lesions were associated with a poor prognosis only in
      patients with PCLBCL-leg. CONCLUSION: With site, morphology, and number of tumors
      taken into account, guidelines for the management of PCLBCL are presented.

PMID- 11504743
TI  - Impact of therapy With chlorambucil, fludarabine, or fludarabine plus
      chlorambucil on infections in patients with chronic lymphocytic leukemia:
      Intergroup Study Cancer and Leukemia Group B 9011.
AB  - PURPOSE: We sought to determine whether therapy with single-agent fludarabine
      compared with chlorambucil alone or the combination of both agents had an impact
      on the incidence and spectrum of infections among a series of previously
      untreated patients with B-cell chronic lymphocytic leukemia (CLL). PATIENTS AND
      METHODS: Five hundred fifty-four previously untreated CLL patients with
      intermediate/high-risk Rai-stage disease were enrolled onto an intergroup
      protocol. Patients were randomized to therapy with chlorambucil, fludarabine, or
      fludarabine plus chlorambucil. Data pertaining to infection were available on 518
      patients. Differences in infections among treatment arms were tested with the
      Kruskal-Wallis, Wilcoxon, and chi(2) tests. RESULTS: A total of 1,107 infections
      (241 major infections) occurred in 518 patients over the infection follow-up
      period (interval from study entry until either reinstitution of initial therapy,
      therapy with a second agent, or death). Patients treated with fludarabine plus
      chlorambucil had more infections than those receiving either single agent (P
      <.0001). Comparing the two single-agent arms, there were more infections on the
      fludarabine arm (P =.055) per month of follow-up. Fludarabine therapy was
      associated with more major infections and more herpesvirus infections compared
      with chlorambucil (P =.008 and P =.004, respectively). Rai stage and best
      response to therapy were not associated with infection. A low serum
      immunoglobulin G was associated with number of infections (P =.02). Age was
      associated with incidence of major infection in the combination arm (P =.004).
      CONCLUSION: Combination therapy with fludarabine plus chlorambucil resulted in
      significantly more infections than treatment with either single agent. Patients
      receiving single-agent fludarabine had more major infections and herpesvirus
      infections compared with chlorambucil-treated patients.

PMID- 11504744
TI  - Prognostic factors analysis of 17,600 melanoma patients: validation of the
      American Joint Committee on Cancer melanoma staging system.
AB  - PURPOSE: The American Joint Committee on Cancer (AJCC) recently proposed major
      revisions of the tumor-node-metastases (TNM) categories and stage groupings for
      cutaneous melanoma. Thirteen cancer centers and cancer cooperative groups
      contributed staging and survival data from a total of 30,450 melanoma patients
      from their databases in order to validate this staging proposal. PATIENTS AND
      METHODS: There were 17,600 melanoma patients with complete clinical, pathologic,
      and follow-up information. Factors predicting melanoma-specific survival rates
      were analyzed using the Cox proportional hazards regression model. Follow-up
      survival data for 5 years or longer were available for 73% of the patients.
      RESULTS: This analysis demonstrated that (1) in the T category, tumor thickness
      and ulceration were the most powerful predictors of survival, and the level of
      invasion had a significant impact only within the subgroup of thin (< or = 1 mm)
      melanomas; (2) in the N category, the following three independent factors were
      identified: the number of metastatic nodes, whether nodal metastases were
      clinically occult or clinically apparent, and the presence or absence of primary
      tumor ulceration; and (3) in the M category, nonvisceral metastases was
      associated with a better survival compared with visceral metastases. A marked
      diversity in the natural history of pathologic stage III melanoma was
      demonstrated by five-fold differences in 5-year survival rates for defined
      subgroups. This analysis also demonstrated that large and complex data sets could
      be used effectively to examine prognosis and survival outcome in melanoma
      patients. CONCLUSION: The results of this evidence-based methodology were
      incorporated into the AJCC melanoma staging as described in the companion
      publication.

PMID- 11504745
TI  - Final version of the American Joint Committee on Cancer staging system for
      cutaneous melanoma.
AB  - PURPOSE: To revise the staging system for cutaneous melanoma under the auspices
      of the American Joint Committee on Cancer (AJCC). MATERIALS AND METHODS: The
      prognostic factors analysis described in the companion publication (this issue),
      as well as evidence from the published literature, was used to assemble the tumor
      node-metastasis criteria and stage grouping for the melanoma staging system.
      RESULTS: Major changes include (1) melanoma thickness and ulceration but not
      level of invasion to be used in the T category (except for T1 melanomas); (2) the
      number of metastatic lymph nodes rather than their gross dimensions and the
      delineation of clinically occult (ie, microscopic) versus clinically apparent
      (ie, macroscopic) nodal metastases to be used in the N category; (3) the site of
      distant metastases and the presence of elevated serum lactic dehydrogenase to be
      used in the M category; (4) an upstaging of all patients with stage I, II, and
      III disease when a primary melanoma is ulcerated; (5) a merging of satellite
      metastases around a primary melanoma and in-transit metastases into a single
      staging entity that is grouped into stage III disease; and (6) a new convention
      for defining clinical and pathologic staging so as to take into account the
      staging information gained from intraoperative lymphatic mapping and sentinel
      node biopsy. CONCLUSION: This revision will become official with publication of
      the sixth edition of the AJCC Cancer Staging Manual in the year 2002.

PMID- 11504746
TI  - Immunomagnetic purging of Ewing's sarcoma from blood and bone marrow:
      quantitation by real-time polymerase chain reaction.
AB  - PURPOSE: A propensity for hematogenous spread with resulting contamination of
      autologous cell products complicates cellular therapies for Ewing's sarcoma. We
      used a new approach to purge artificially contaminated cellular specimens of
      Ewing's sarcoma and show the capacity for real-time polymerase chain reaction
      (PCR) to quantify the contamination level of Ewing's sarcoma in such specimens.
      PATIENTS AND METHODS: Binding of monoclonal antibody (MoAb) 8H9 to Ewing's
      sarcoma cell lines and normal hematopoietic cells was studied using flow
      cytometry. Using real-time PCR--based amplification of t(11;22), levels of
      Ewing's contamination of experimental and clinical cellular products were
      monitored. Purging was accomplished using immunomagnetic-based depletion.
      Monitoring of the function of residual hematopoietic progenitors and T cells was
      performed using functional assays. RESULTS: MoAb 8H9 shows binding to Ewing's
      sarcoma but spares normal hematopoietic tissues. Nested real-time PCR is capable
      of detecting contaminating Ewing's sarcoma cells with a sensitivity of one cell
      in 10(6) normal cells. After 8H9-based purging, a 2- to 3-log reduction in
      contaminating Ewing's sarcoma was shown by real-time PCR, with purging to PCR
      negativity at levels of contamination of 1:10(6). Levels of contamination in
      clinical samples ranged from 1:10(5) to 10(6). Therefore, 8H9-based purging of
      clinical samples is predicted to reduce tumor cell contamination to a level below
      the limit of detection of PCR. CONCLUSION: These results demonstrate a new
      approach for purging contaminated cellular products of Ewing's sarcoma and
      demonstrate the capacity of real-time PCR to provide accurate quantitative
      estimates of circulating tumor burden in this disease.

PMID- 11504747
TI  - Prognostic significance of a novel hypoxia-regulated marker, carbonic anhydrase
      IX, in invasive breast carcinoma.
AB  - PURPOSE: To assess the frequency of expression and the prognostic significance of
      a hypoxia-regulated marker, carbonic anhydrase IX (CA IX), in a cohort of
      patients with invasive breast cancer. PATIENTS AND METHODS: CA IX expression was
      evaluated by immunohistochemistry with a murine monoclonal antibody, M75, in a
      series of 103 women treated surgically for invasive breast cancer. The majority
      of patients were treated with adjuvant hormonal or chemotherapy. The frequency of
      CA IX expression, its association with recognized prognostic factors, and the
      relationship with outcome was evaluated by univariate and multivariate
      statistical analyses. RESULTS: CA IX expression was present in 49 (48%) of 103
      cases. The level of CA IX expression was found to be significantly associated
      with tumor necrosis (P <.001), higher grade (P =.02), and negative estrogen
      receptor status (P <.001). Furthermore, CA IX expression was associated with a
      higher relapse rate (P =.004) and a worse overall survival (P =.001). By
      multivariate analysis, CA IX was also shown to be an independent predictive
      factor for overall survival (hazard ratio, 2.61; 95% confidence interval, 1.01 to
      6.75, P =.05). CONCLUSION: CA IX expression was associated with worse relapse
      free survival and overall survival in an unselected cohort of patients with
      invasive breast carcinoma. The potential role of CA IX as a marker of hypoxia
      within breast carcinomas was also indicated by a significant association with
      necrosis. Further work assessing its prognostic significance in breast cancer is
      warranted, particularly interactions with radiotherapy and chemotherapy
      resistance.

PMID- 11504748
TI  - Epithelial cells in bone marrow of breast cancer patients at time of primary
      surgery: clinical outcome during long-term follow-up.
AB  - PURPOSE: To evaluate the detection of epithelial cells in bone marrow of breast
      cancer patients as an indicator of metastatic disease. PATIENTS AND METHODS:
      Between 1989 and 1994, bone marrow biopsies were performed on 393 breast cancer
      patients during primary surgery. Specimens were stained immunocytochemically for
      epithelial cells expressing cytokeratins or the epithelial membrane antigen. The
      long-term outcomes of these patients were analyzed in this study. RESULTS: In 166
      of 393 patients, epithelial cells were found in bone marrow (BM) aspirates. These
      patients were designated BM+. The rate of tumor recurrence or cancer-related
      death was significantly higher in BM+ patients than in BM- patients. Multivariate
      analysis using the Cox regression model revealed BM status as a prognostic
      parameter independent of tumor size and axillary lymph node status. However,
      tumor size and axillary lymph node status were clearly superior prognostic
      parameters. CONCLUSION: Disseminated epithelial cells in BM are associated with
      poor clinical outcome in breast cancer patients. However, the presence of these
      cells is not a sufficient parameter to predict growing metastases in the majority
      of patients, suggesting that epithelial cells in the BM of breast cancer patients
      at the time of surgery have limited metastatic potential. The role of these cells
      needs to be further evaluated.

PMID- 11504749
TI  - Second allogeneic bone marrow transplantation in acute leukemia: results of a
      survey by the European Cooperative Group for Blood and Marrow Transplantation.
AB  - PURPOSE: Leukemic relapse is the most frequent cause of treatment failure after
      allogeneic hematopoietic stem-cell transplantation (HSCT). To identify prognostic
      factors affecting the outcome of second HSCT, we performed a retrospective study
      on patients with acute leukemia (AL) undergoing second HSCT who reported to the
      Acute Leukemia Working Party of the European Cooperative Group for Blood and
      Marrow Transplantation registry. PATIENTS AND METHODS: One hundred seventy
      patients who received second HSCTs for AL experienced relapse after first HSCTs
      were performed from 1978 to 1997. Status at second HSCT, time between first and
      second HSCT, conditioning regimen, source of stem cells, treatment-related
      mortality (TRM), acute graft-versus-host disease (aGVHD), leukemia-free survival
      (LFS), overall survival (OS), and relapse were considered. RESULTS: Engraftment
      occurred in 97% of patients. Forty-two patients were alive at last follow-up,
      with a 5-year OS rate of 26%. The 5-year probability for TRM, LFS, and relapse
      was 46%, 25%, and 59%, respectively. Grade > or = 2 aGVHD occurred in 59% of
      patients, and chronic GVHD occurred in 32%. In multivariate analysis, diagnosis,
      interval to relapse after first HSCT > 292 days, aGVHD at first HSCT, complete
      remission status at second HSCT, use of total-body irradiation at second HSCT,
      acute GVHD at second HSCT, and use of bone marrow as source of stem cells at
      second HSCT were associated with better outcome. CONCLUSION: Second HSCT
      represents an effective therapeutic option for AL patients relapsed after
      allogeneic HSCT, with a 3-year LFS rate of 52% for the subset of patients who
      experienced relapse more than 292 days after receiving the first HSCT and who
      were in remission before receiving the second HSCT.

PMID- 11504750
TI  - Acute and chronic graft-versus-host disease after allogeneic peripheral-blood
      stem-cell and bone marrow transplantation: a meta-analysis.
AB  - PURPOSE: Controversy exists as to whether the incidence of graft-versus-host
      disease (GVHD) is increased after peripheral-blood stem-cell transplantation
      (PBSCT) when compared with bone marrow transplantation (BMT). We performed a meta
      analysis of all trials comparing the incidence of acute and chronic GVHD after
      PBSCT and BMT reported as of June, 2000. Secondary analyses examined relapse
      rates after the two procedures. METHODS: An extensive MEDLINE search of the
      literature was undertaken. Primary authors were contacted for clarification and
      completion of missing information. A review of cited references was also
      undertaken. Sixteen studies (five randomized controlled trials and 11 cohort
      studies) were included in this analysis. Data was extracted by two pairs of
      reviewers and analyzed for the outcomes of interest. Meta-analyses, regression
      analyses, and assessments of publication bias were performed. RESULTS: Using a
      random effects model, the pooled relative risk (RR) for acute GVHD after PBSCT
      was 1.16 (95% confidence interval [CI], 1.04 to 1.28; P=.006) when compared with
      traditional BMT. The pooled RR for chronic GVHD after PBSCT was 1.53 (95% CI,
      1.25 to 1.88; P <.001) when compared with BMT. The RR of developing clinically
      extensive chronic GVHD was 1.66 (95% CI, 1.35 to 2.05; P <.001). The excess risk
      of chronic GVHD was explained by differences in the T-cell dose delivered with
      the graft in a meta-regression model that did not reach statistical significance.
      There was a trend towards a decrease in the rate of relapse after PBSCT (RR =
      0.81; 95% CI, 0.62 to 1.05). CONCLUSION: Both acute and chronic GVHD are more
      common after PBSCT than BMT, and this may be associated with lower rates of
      malignant relapse. The magnitude of the transfused T-cell load may explain the
      differences in chronic GVHD risk.

PMID- 11504751
TI  - Prognostic significance of pathologic features in localized prostate cancer
      treated with radical prostatectomy: implications for staging systems and
      predictive models.
AB  - PURPOSE: Although predicting outcome for men with clinically localized prostate
      cancer (PC) has improved, the staging system and nomograms used to do this are
      based on results from the North American health system. To be internationally
      applicable, these models require testing in cohorts from a variety of different
      health systems based on the predominant PC case identification methods used.
      PATIENTS AND METHODS: We studied 732 men with localized PC treated with radical
      prostatectomy and no preoperative therapy between 1986 and 1999 at one Australian
      institution to determine the effect of clinicopathologic features on disease-free
      survival. RESULTS: Preoperative serum prostate-specific antigen (PSA)
      concentration, Gleason score, pathologic stage, and year of surgery were
      independent predictors of outcome. Although margin status demonstrated only a
      trend toward significance in multivariate modeling overall, it proved to be
      independent in subgroups based on later year of surgery (1986 to 1994 v 1995 to
      1998), preoperative PSA of less than 10 ng/mL, and Gleason score > or = 7.
      Adjuvant radiation therapy improved disease-free survival rates in patients with
      multiple surgical margin involvement. CONCLUSION: This work confirms the
      prognostic significance of pathologic stage, Gleason score, and preoperative
      serum PSA. In the context of a contemporaneous screening effect in Australia,
      these findings may have implications for methods that predict outcome following
      surgery as screening becomes more prevalent in a population. The independent
      prognostic effect of margin status may alter with an increase in the proportion
      of screening-identified PCs. Staging systems and nomograms that predict outcome
      following surgery require validation in cohorts with different health practices
      before being universally applied.

PMID- 11504752
TI  - BAG-1 immunostaining and survival in early breast cancer.

PMID- 11504753
TI  - Too early to say that pregnancy has an antitumor effect on breast cancer.

PMID- 11504754
TI  - Role of population-based studies in assessing genetic cancer risk.

PMID- 11504755
TI  - Molecular targeting: the new challenge in lung cancer prevention.

PMID- 11504756
TI  - Embryonic stem cell debate brings politics, ethics to the bench.

PMID- 11504757
TI  - Clinical trials provision makes way into patients' bill of rights.

PMID- 11504759
TI  - Canadians push national cancer strategy.

PMID- 11504762
TI  - Cancer screening in older patients: making decisions about age cutoffs.

PMID- 11504763
TI  - BRCA1: lessons learned from the breast cancer gene.

PMID- 11504764
TI  - Stat bite: U.S. incidence rates for selected childhood cancers.

PMID- 11504766
TI  - Epoetin treatment of anemia associated with cancer therapy: a systematic review
      and meta-analysis of controlled clinical trials.
AB  - Epoetin treatment offers an attractive but costly alternative to red blood cell
      transfusion for managing anemia associated with cancer therapy. The goal of this
      review is to facilitate more efficient use of epoetin by 1) quantifying the
      effects of epoetin on the likelihood of transfusion and on quality of life in
      patients with cancer treatment-related anemia and 2) evaluating whether outcomes
      are superior when epoetin treatment is initiated at higher hemoglobin thresholds.
      Two independent reviewers followed a prospective protocol for identifying
      studies. Outcomes data were combined with the use of a random-effects meta
      analysis model. Double-blind, randomized, controlled trials that minimized
      patient exclusions were defined as higher quality for sensitivity analysis;
      randomized but unblinded trials and trials with excessive exclusions were
      included in the meta-analysis but were defined as lower quality. Twenty-two
      trials (n = 1927) met inclusion criteria, and 12 (n = 1390) could be combined for
      estimation of odds of transfusion. Epoetin decreased the percentage of patients
      transfused by 9%-45% in adults with mean baseline hemoglobin concentrations of 10
      g/dL or less (seven trials; n = 1080), by 7%-47% in those with hemoglobin
      concentrations greater than 10 g/dL but less than 12 g/dL (seven trials; n =
      431), and by 7%-39% in those with hemoglobin concentrations of 12 g/dL or higher
      (five trials; n = 308). In sensitivity analysis, the combined odds ratio for
      transfusion in epoetin-treated patients as compared with controls was 0.45 (95%
      confidence interval [CI] = 0.33 to 0.62) in higher quality studies and 0.14 (95%
      CI = 0.06 to 0.31) in lower quality studies. The number of patients needed to
      treat to prevent one transfusion is 4.4 for all studies, 5.2 for higher quality
      studies, and 2.6 for lower quality studies. Only studies with mean baseline
      hemoglobin concentrations of 10 g/dL or less reported statistically significant
      effects of epoetin treatment on quality of life; quality-of-life data were
      insufficient for meta-analysis. No studies addressed epoetin's effects on anemia
      related symptoms. We conclude that epoetin reduces the odds of transfusion for
      cancer patients undergoing therapy. Evidence is insufficient to determine whether
      initiating epoetin earlier spares more patients from transfusion or results in
      better quality of life than waiting until hemoglobin concentrations decline to
      nearly 10 g/dL.

PMID- 11504767
TI  - Family history of breast and ovarian cancers and BRCA1 and BRCA2 mutations in a
      population-based series of early-onset breast cancer.
AB  - BACKGROUND: BRCA1 and BRCA2 are the two major susceptibility genes involved in
      hereditary breast cancer. This study was undertaken to provide reliable
      population-based estimates of genetic influence and to characterize the nature
      and prevalence of BRCA1 and BRCA2 germline mutations in early-onset breast
      cancer. METHODS: In a series comprising all women diagnosed with breast cancer
      under the age of 41 years in southern Sweden during 1990 through 1995 (n = 262),
      family history of cancer was evaluated in 95% (n = 250) of the case subjects and
      germline mutations in BRCA1 and BRCA2 were analyzed in 89% (n = 234). All
      statistical tests were two-sided. RESULTS: A total of 97 case subjects had at
      least one first- or second-degree relative with breast or ovarian cancer; 34
      (14%; 95% confidence interval [CI] = 9.6% to 18%) cases had at least two first-
      or second-degree relatives, 22 (8.8%; 95%CI = 5.3% to 12%) had one first-degree
      relative, and 41 (16%; 95% CI = 12% to 21%) had one second-degree relative with
      either cancer. If two females affected with breast or ovarian cancer who were
      related through an unaffected male were also defined as first-degree relatives,
      then a higher number of case subjects, 120 (48%; 95% CI = 42% to 54%), had at
      least one first-degree or second-degree relative with breast or ovarian cancer.
      Sixteen (6.8%; 95% CI = 4.0% to 11%) BRCA1 mutation carriers and five (2.1%; 95%
      CI = 0.70% to 4.9%) BRCA2 mutation carriers were identified. Among case subjects
      with one first- or more than one first- or second-degree relative with breast or
      ovarian cancer, BRCA mutations were more frequent (P<.001) than among the case
      subjects without this degree of family history. BRCA mutations were also
      statistically significantly more common among women with bilateral breast cancer
      than among women with unilateral breast cancer (P =.002). BRCA mutations were
      more common among younger case subjects than among older ones (P =.0027).
      CONCLUSIONS: Almost half (48%) of women in southern Sweden with early-onset
      breast cancer have some family history of breast or ovarian cancer, and 9.0% of
      early-onset breast cancer cases are associated with a germline mutation in BRCA1
      or BRCA2. Mutation carriers were more prevalent among young women, women with at
      least one first- or second-degree relative with breast or ovarian cancer, and
      women with bilateral breast cancer.

PMID- 11504768
TI  - Carnosic acid and promotion of monocytic differentiation of HL60-G cells
      initiated by other agents.
AB  - BACKGROUND: Carnosic acid is a plant-derived polyphenol food preservative with
      chemoprotective effects against carcinogens when tested in animals. Recently, we
      showed that carnosic acid potentiates the effects of 1alpha,25-dihydroxyvitamin
      D3 (1alpha,25[OH]2D3) and of all-trans-retinoic acid (ATRA) on differentiation of
      human leukemia cells. We now examine the mechanisms associated with carnosic acid
      induced enhancement of cell differentiation (in subline HL60-G) initiated by
      1alpha,25(OH)2D3, ATRA, or 12-O-tetradecanoylphorbol-13-acetate (TPA). METHODS:
      We evaluated monocytic differentiation markers (CD11b, CD14, and monocytic serine
      esterase), cell cycle parameters, and cell proliferation rates after treatment of
      cells with different agents with or without carnosic acid. We also assessed the
      abundance of the vitamin D receptor (VDR), retinoid X receptor (RXR)-alpha,
      retinoic acid receptor (RAR)-alpha, and cell cycle-associated proteins by
      immunoblot analysis (p27, early growth response gene [EGR]-1, and p35Nck5a), the
      expression of corresponding genes by reverse transcription-polymerase chain
      reaction (RT-PCR), and the activity of VDR by electrophoretic mobility shift
      analysis. The two-sided nonparametric Kruskal-Wallis one-way analysis-of-variance
      test with Dunn's adjustment was used for statistical analyses. RESULTS: Monocytic
      differentiation induced by low (1 nM) concentrations of 1alpha,25(OH)2D3, ATRA,
      or TPA was enhanced by carnosic acid (10 microM), as shown by the increased
      expression of monocytic serine esterase (P<.001, P<.001, and P =.043,
      respectively) and of CD11b (P =.008, P =.046, and P =.041, respectively).
      Increased expression of CD14 was seen only for 1alpha,25(OH)2D3 and ATRA (P =.009
      and P =.048, respectively) and also for several cell cycle-associated proteins.
      Carnosic acid in combination with 1alpha,25(OH)2D3 and ATRA resulted in decreased
      cell proliferation and blocked the cell cycle transition from G1 to S phase
      (P<.05). Carnosic acid alone increased the expression of VDR and RXR-alpha, but
      the expression was greatly enhanced in the presence of 1alpha,25(OH)2D3 and ATRA.
      In combination with TPA, carnosic acid potentiated the expression of VDR and RAR
      alpha. CONCLUSION: Carnosic acid enhances a program of gene expression consistent
      with 1alpha,25(OH)2D3-, ATRA-, or TPA-induced monocytic differentiation of HL60-G
      cells.

PMID- 11504769
TI  - Effects of orally active taxanes on P-glycoprotein modulation and colon and
      breast carcinoma drug resistance.
AB  - BACKGROUND: The taxane paclitaxel (Taxol) is often of limited efficacy in
      chemotherapeutic regimens because some cancer cells express high levels of the
      efflux pump, P-glycoprotein (Pgp), which removes the drug from the cells. The
      orally active paclitaxel analog IDN-5109 has been reported to overcome Pgp
      mediated drug resistance. We tested whether IDN-5109 acts by modulating Pgp
      activity. METHODS: Human MDA435/LCC6mdr1 and MDA435/LCC6 breast carcinoma cells,
      which express and do not express Pgp, respectively, were incubated with [3H]IDN
      5109 and paclitaxel to determine intracellular drug accumulation. Flow cytometry
      was used to analyze intracellular retention of two Pgp substrates, rhodamine 123
      (Rh-123) and doxorubicin, in both breast carcinoma cell lines and in human colon
      carcinoma cells (SW-620, DLD1, and HCT-15, whose Pgp levels vary) treated with
      different taxanes. The effects of IDN-5109 and paclitaxel on tumor growth in vivo
      were studied with the use of tumors established through xenografts of Pgp
      expressing SW-620 and DLD1 cells in severe combined immunodeficiency mice. All
      statistical tests were two-sided. RESULTS: Pgp-expressing cells treated with IDN
      5109 or with the taxane-based drug resistance reversal agent tRA96023, which
      blocks Pgp activity, retained 8.1- and 9.4-fold more Rh-123 (P =.0001),
      respectively, and 1.7- and 1.9-fold more doxorubicin (P =.001), respectively,
      than cells treated with paclitaxel. Non-Pgp-expressing cells treated similarly
      demonstrated no increased retention of either substrate. MDA435/LCC6mdr1 cells
      retained 5.3-fold more [3H]IDN-5109 than [3H]paclitaxel after 2 hours (P =.01).
      IDN-5109 showed statistically significantly higher tumor growth inhibition than
      paclitaxel against the SW-620 xenograft (P =.003). CONCLUSIONS: IDN-5109
      modulates Pgp activity, resulting in superior tumor growth inhibition against Pgp
      expressing tumors as compared with paclitaxel. IDN-5109 may broaden the spectrum
      of taxane use to include colon tumors.

PMID- 11504770
TI  - PTEN mutation, EGFR amplification, and outcome in patients with anaplastic
      astrocytoma and glioblastoma multiforme.
AB  - BACKGROUND: Survival of patients with anaplastic astrocytoma is highly variable.
      Prognostic markers would thus be useful to identify clinical subsets of such
      patients. Because specific genetic alterations have been associated with
      glioblastoma, we investigated whether similar genetic alterations could be
      detected in patients with anaplastic astrocytoma and used to identify those with
      particularly aggressive disease. METHODS: Tissue specimens were collected from
      174 patients enrolled in Mayo Clinic Cancer Center and North Central Cancer
      Treatment Group clinical trials for newly diagnosed gliomas, including 63 with
      anaplastic astrocytoma and 111 with glioblastoma multiforme. Alterations of the
      EGFR, PTEN, and p53 genes and of chromosomes 7 and 10 were examined by
      fluorescence in situ hybridization, semiquantitative polymerase chain reaction,
      and DNA sequencing. All statistical tests were two-sided. RESULTS: Mutation of
      PTEN, amplification of EGFR, and loss of the q arm of chromosome 10 were
      statistically significantly less common in anaplastic astrocytoma than in
      glioblastoma multiforme (P =.033, P =.001, and P<.001, respectively), and
      mutation of p53 was statistically significantly more common (P<.001). Univariate
      survival analyses of patients with anaplastic astrocytoma identified PTEN (P
      =.002) and p53 (P =.012) mutations as statistically significantly associated with
      reduced and prolonged survival, respectively. Multivariate Cox analysis of
      patients with anaplastic astrocytoma showed that PTEN mutation remained a
      powerful prognostic factor after adjusting for patient age, on-study performance
      score, and extent of tumor resection (hazard ratio = 4.34; 95% confidence
      interval = 1.82 to 10.34). Multivariate classification and regression-tree
      analysis of all 174 patients identified EGFR amplification as an independent
      predictor of prolonged survival in patients with glioblastoma multiforme who were
      older than 60 years of age. CONCLUSION: PTEN mutation and EGFR amplification are
      important prognostic factors in patients with anaplastic astrocytoma and in older
      patients with glioblastoma multiforme, respectively.

PMID- 11504771
TI  - Effects of N-(4-hydroxyphenyl)retinamide on hTERT expression in the bronchial
      epithelium of cigarette smokers.
AB  - BACKGROUND: Telomerase activation plays a critical role in tumorigenesis. To
      determine the role of telomerase in early lung carcinogenesis and as a potential
      biomarker in chemoprevention trials, we analyzed the expression of the human
      telomerase reverse transcriptase catalytic subunit (hTERT) in bronchial biopsy
      specimens from cigarette smokers who were enrolled in a randomized, double
      blinded, placebo-controlled chemoprevention trial of N-(4
      hydroxyphenyl)retinamide (4-HPR). METHODS: We obtained biopsy specimens from six
      predetermined sites in the bronchial tree from the 57 participants, before
      treatment and 6 months after treatment with 4-HPR or placebo. We used in situ
      hybridization to examine hTERT messenger RNA (mRNA) expression in 266
      pretreatment (baseline) and post-treatment site-paired biopsy specimens from 27
      patients in the 4-HPR-treated group and from 30 patients in the placebo-treated
      group. All statistical tests were two-sided. RESULTS: At baseline, 62.4% (95%
      confidence interval [CI] = 53.9% to 71%) of the biopsy specimens obtained from
      the group treated with 4-HPR and 65.2% (95% CI = 57.4% to 73.1%) of the biopsy
      specimens obtained from the placebo-treated group expressed hTERT mRNA. After 6
      months, 45.6% (95% CI = 36.9% to 54.3%) of the biopsy specimens obtained from the
      4-HPR-treated group and 68.1% (95% CI = 60.4% to 75.8%) of the biopsy specimens
      obtained from the placebo-treated group expressed hTERT mRNA. The reduction in
      hTERT expression observed between the two treatment groups over time was
      statistically significant (P =.01) when we used the biopsy site as the unit of
      analysis, but not when we used the individual as the unit of analysis (P =.37).
      CONCLUSIONS: Telomerase is frequently reactivated in the lungs of cigarette
      smokers. The modulation of hTERT expression in 4-HPR-treated smokers suggests
      that a novel molecular mechanism underlies the potential chemopreventive
      properties of 4-HPR. hTERT expression is a promising potential biomarker for risk
      assessment and for the evaluation of the efficacy of chemopreventive agents in
      lung carcinogenesis.

PMID- 11504772
TI  - Effect of age on risk of second primary colorectal cancer.

PMID- 11504773
TI  - Re: Hutchinson Smoking Prevention Project: long-term randomized trial in school
      based tobacco use prevention--results on smoking.

PMID- 11504774
TI  - Re: Hutchinson Smoking Prevention Project: long-term randomized trial in school
      based tobacco use prevention--results on smoking.

PMID- 11504775
TI  - Re: Hutchinson Smoking Prevention Project: long-term randomized trial in school
      based tobacco use prevention--results on smoking.

PMID- 11504778
TI  - Drug synergism: its detection and applications.
AB  - Two drugs that produce overtly similar effects will sometimes produce exaggerated
      or diminished effects when used concurrently. A quantitative assessment is
      necessary to distinguish these cases from simply additive action. This
      distinction is based on the classic pharmacologic definition of additivity that,
      briefly stated, means that each constituent contributes to the effect in accord
      with its own potency. Accordingly, the relative potency of the agents, not
      necessarily constant at all effect levels, allows a calculation using dose pairs
      to determine the equivalent of either agent and the effect by using the
      equivalent in the dose-response relation of the reference compound. The
      calculation is aided by a popular graph (isobologram) that provides a visual
      assessment of the interaction but also requires independent statistical analysis.
      The latter can be accomplished from calculations that use the total dose in a
      fixed-ratio combination along with the calculated additive total dose for the
      same effect. Different methods may be used, and each is applicable to experiments
      in which a single drug is given at two different sites. When departures from
      additivity are found, whether in "two-drug" or "two-site" experiments, the
      information is useful in designing new experiments for illuminating mechanisms.
      Several examples, mainly from analgesic drug studies, illustrate this
      application. Even when a single drug (or site) is used, its introduction places
      it in potential contact with a myriad of chemicals already in the system, a fact
      that underscores the importance of this topic in other areas of biological
      investigation.

PMID- 11504779
TI  - Growth factor signaling in cell survival: implications for cancer treatment.
AB  - Cells of multicellular organisms require extracellular signals to survive.
      Numerous studies have implicated a variety of intracellular signaling pathways,
      including PI-3 kinase/Akt, Ras/mitogen-activated protein kinase, and Jak/signal
      transducers and activators of transcription, as effectors of these extracellular
      trophic factors. Binding of growth factors to their respective receptors results
      in the activation of individual and combined pathways resulting in pleiotropic
      effects on cellular biochemistry. Over the past decade, investigation of these
      pathways has provided insight into the mechanism of cell survival and apoptosis
      itself. The results of these studies are providing new clues for therapeutic
      intervention in human disease. In this review, we focus on advances in our
      current understanding of the receptor signaling pathways that regulate apoptosis.
      Implications for the pharmacological manipulation of apoptosis in the treatment
      of cancer are also discussed.

PMID- 11504780
TI  - Oxidative inactivation of nitric oxide and endothelial dysfunction in stroke
      prone spontaneous hypertensive rats.
AB  - This study tested the hypothesis that increased nitric oxide (NO) inactivation
      and concurrent peroxynitrite formation is responsible for endothelial dysfunction
      in the spontaneously hypertensive stroke-prone rat (SHRSP). In SHRSP, the aortic
      vasorelaxation to acetylcholine (ACh) was decreased (p < 0.05), but NO production
      was unchanged. Nitrotyrosine staining, a footprint of peroxynitrite (ONOO(-))
      formation, was detected. Exposure of SHRSP to a high-salt, high-fat diet (SFD)
      further exacerbated hypertension and accelerated end-organ disease. A severe
      endothelial dysfunction [maximal ACh relaxation: 49.8 +/- 2.1 versus 94.5 +/-
      1.8% in Wistar-Kyoto rats (WKY), p < 0.01], increased basal NO production (482 +/
      17 versus 356 +/- 21 nM, p < 0.01), decreased ACh-stimulated NO production (57
      +/- 6 versus 112 +/- 6 nM, p < 0.01), extensive inducible NO synthase and
      nitrotyrosine staining, elevated nitrotyrosine content (21-fold increase over
      WKY), and a high percentage of cells with DNA damage were observed in the aortic
      tissues from these animals. Treatment of SHRSP on SFD with carvedilol restored
      ACh-induced vasorelaxation and NO production, inhibited nitrotyrosine formation,
      reduced vascular cell DNA damage, and reduced end-organ injury. These data
      demonstrate that endothelial dysfunction was caused by increased NO inactivation
      alone (SHRSP) or in combination with decreased NO production from endothelial NO
      synthase (SHRSP on SFD). Antioxidant treatment with carvedilol exerted
      significant vascular protective effects, attenuated end-organ damage, and
      decreased mortality under these conditions.

PMID- 11504781
TI  - Pharmacokinetics and tissue distribution of SB-251353, a novel human CXC
      chemokine, after intravenous administration to mice.
AB  - The pharmacokinetics and tissue distribution of SB-251353, a novel truncated form
      of the human CXC chemokine growth-related gene product beta, were studied after
      intravenous administration to the mouse (0.1--250 mg/kg). At the lowest dose, the
      clearance exceeded blood flow to the kidney. As the dose increased, clearance
      approached the glomerular filtration rate in the mouse. Clearance of this
      chemokine may be mediated by its pharmacologic receptor, CXCR2, via endocytosis
      with subsequent lysosomal degradation, as has been observed for several growth
      and hematopoietic factors. Apparent distribution volumes were high (> or =1
      l/kg). Moderate binding to the Duffy antigen/receptor for chemokines on
      erythrocytes was observed. Consistent with the pharmacokinetic analysis,
      microscopic autoradiography showed uptake into renal proximal tubule epithelial
      cells. Limited excretion of SB-251353 in the urine (<2%) was consistent with
      catabolism of the chemokine in the tubules. Binding to hepatic sinusoids and
      connective tissue in the dermis was observed. This possibly reflected interaction
      of SB-251353 with heparin sulfate proteoglycan and may explain the large
      distribution volumes. This first study of the disposition of a chemokine provides
      insight into mechanism of action and physiological factors that may influence
      chemokine pharmacodynamics.

PMID- 11504782
TI  - Prevention of neutrophil-mediated hepatic ischemia/reperfusion injury by
      superoxide dismutase and catalase derivatives.
AB  - Our previous study demonstrated that the combination of mannosylated superoxide
      dismutase (Man-SOD) and succinylated catalase (Suc-CAT), both of which are
      designed to be targeted to liver nonparenchymal cells, is a promising approach to
      prevent the initial phase of hepatic ischemia/reperfusion injury induced by
      occlusion of the portal vein for 30 min followed by a 1-h reperfusion in mice. In
      this study, the preventive effects of these agents were examined on late-phase
      injury mediated by infiltrating neutrophils, a more severe condition than the
      initial one. Administration of Suc-CAT alone or with Man-SOD to mice undergoing
      hepatic ischemia/reperfusion significantly suppressed the expression of
      intercellular adhesion molecule-1 along the hepatic sinusoid and prevented
      neutrophil infiltration in the liver. Man-SOD and Suc-CAT also prevented the
      increase in plasma glutamic pyruvic transaminase and glutamic oxaloacetic
      transaminase activities after reperfusion lasting 3 and 6 h. Histological
      evaluation of liver tissues confirmed the efficacy of this treatment, suggesting
      that these SOD and catalase derivatives have the ability to suppress neutrophil
      induced hepatic injury. These results demonstrate that targeted delivery of
      antioxidant enzymes to liver nonparenchymal cells is a promising approach to
      reducing the reactive oxygen species produced by Kupffer cells and neutrophils
      infiltrating into the tissue. Since Suc-CAT is partially taken up by hepatocytes
      via a catalase-specific uptake mechanism, such a fraction could also be involved
      in its preventive effect against the injury.

PMID- 11504783
TI  - Inhibition of tumor necrosis factor-alpha (TNF-alpha) production and arthritis in
      the rat by GW3333, a dual inhibitor of TNF-alpha-converting enzyme and matrix
      metalloproteinases.
AB  - Tumor necrosis factor-alpha (TNF)-converting enzyme (TACE) cleaves the precursor
      form of TNF, allowing the mature form to be secreted into the extracellular
      space. GW3333, a dual inhibitor of TACE and matrix metalloproteinases (MMPs), was
      compared with an anti-TNF antibody to evaluate the importance of soluble TNF and
      MMPs in rat models of arthritis. Oral administration of GW3333 completely blocked
      increases in plasma TNF after LPS for up to 12 h. In a model wherein intrapleural
      zymosan injection causes an increase in TNF in the pleural cavity, GW3333
      completely inhibited the increase in TNF in the pleural cavity for 12 h. Under
      these dosing conditions, the plasma levels of unbound GW3333 were at least 50
      fold above the IC(50) values for inhibition of individual MMPs in vitro. In a
      model wherein bacterial peptidoglycan polysaccharide polymers reactivate a local
      arthritis response in the ankle, a neutralizing anti-TNF antibody completely
      blocked the ankle swelling over the 3-day reactivation period. GW3333
      administered b.i.d. over the same period also inhibited ankle swelling, with the
      highest dose of 80 mg/kg being slightly less active than the anti-TNF antibody.
      In a 21-day adjuvant arthritis model, the anti-TNF antibody did not inhibit the
      ankle swelling or the joint destruction, as assessed by histology or radiology.
      GW3333, however, showed inhibition of both ankle swelling and joint destruction.
      In conclusion, GW3333 is the first inhibitor with sufficient duration of action
      to chronically inhibit TACE and MMPs in the rat. The efficacy of GW3333 suggests
      that dual inhibitors of TACE and matrix metalloproteinases may prove therapeutic
      as antiarthritics.

PMID- 11504784
TI  - Cellular depolarization of neurons in the locus ceruleus region of the guinea pig
      associated with the development of tolerance to opioids.
AB  - These experiments were designed to test two hypotheses: 1) the tolerance induced
      by morphine pellet implantation in guinea pigs will result in subsensitivity of
      cells in the locus ceruleus (LC), not only to morphine, but to another agonist
      acting on a different receptor and transduction system, namely the gamma
      aminobutyric acid(A) receptor agonist, muscimol; and 2) The nonspecific
      (heterologous) tolerance would be associated with a partial depolarization of the
      tolerant cells and a decrease in the contribution of electrogenic Na(+)/K(+)
      pumping. Extracellular recording from LC neurons in brain slices from animals
      implanted with either morphine or placebo pellets established that the tolerant
      preparations were subsensitive to both morphine and muscimol. Immunocytochemical
      analysis identified the alpha(3)-subunit as the primary isoform of the Na(+)/K(+)
      pump in the cells under investigation. Whole-cell patch clamp recording of
      neurons in brain slices demonstrated that, with electrodes containing 20 mM Na(+)
      (approximating [Na](i)), tolerant cells were significantly depolarized by a mean
      of 6.7 mV. Dialysis with antibody specific for the alpha(3)-isoform from patch
      pipettes produced depolarization of both control and tolerant cells. However, the
      depolarizing effect of the antibody was less in tolerant cells, suggesting a
      lesser degree of electrogenic Na(+) pumping. Furthermore, the presence of
      antibody reduced the membrane potentials of tolerant and placebo cells to equal
      values, suggesting that the diffusion potentials were not different. In contrast,
      antibody specific for the alpha(1)-subunit isoform in the pipettes had no effect
      on membrane potential in either control or tolerant cells. In conclusion, both
      hypotheses were supported.

PMID- 11504785
TI  - Protein kinase A-dependent and -independent effects of isoproterenol in rat
      isolated mesenteric artery: interactions with levcromakalim.
AB  - The effect of beta-adrenoceptor activation on levcromakalim-induced relaxation
      was investigated in myograph-mounted rat mesenteric arteries. The nonselective
      beta-adrenoceptor agonist isoproterenol (at a concentration causing approximately
      30% relaxation of methoxamine-induced tone) potentiated relaxation to
      levcromakalim; higher concentrations exerted no additional effect. The modulatory
      and relaxant effects of isoproterenol were inhibited by the beta(1)-adrenoceptor
      antagonist atenolol, but the ATP-sensitive K(+) (K(ATP)) channel inhibitor
      glibenclamide did not inhibit relaxations to isoproterenol. The protein kinase A
      inhibitor Rp-adenosine 3',5'-cyclic monophosphothioate triethylamine (Rp-cAMPS)
      inhibited the ability of isoproterenol to modulate levcromakalim relaxation.
      However, neither Rp-cAMPS nor N-[2-(p-bromocinnamylamino)ethyl]-6
      isoquinolinesulfonamide (H-89) (another protein kinase A inhibitor) markedly
      reduced isoproterenol-induced relaxation, although Rp-cAMPS inhibited relaxations
      induced by forskolin (an adenylyl cyclase activator). Iberiotoxin (50 nM), an
      inhibitor of large conductance Ca(2+)-activated K(+) channels (BK(Ca)),
      attenuated isoproterenol relaxation. Moreover, both Rp-cAMPS and H-89 caused
      inhibition of the effects of isoproterenol in the presence of iberiotoxin,
      whereas glibenclamide did not. We conclude that isoproterenol modulates the
      actions of levcromakalim through beta(1)-adrenoceptors and protein kinase A, even
      though K(ATP) channels do not contribute to its relaxant effects. However, the
      major relaxant mechanism for isoproterenol appears to be protein kinase A
      independent activation of BK(Ca), with cyclic AMP-dependent mechanisms only being
      unmasked when the BK(Ca) mechanism is inhibited. Although direct G protein
      mediated activation of BK(Ca) has been demonstrated previously in
      electrophysiological studies of single smooth muscle cells, this is the first
      time that such a mechanism has been shown to be functionally important in an
      intact blood vessel preparation.

PMID- 11504786
TI  - Differential sensitivity of mesencephalic neurons to inhibition of phosphatase
      2A.
AB  - Disturbance in phosphorylation/dephosphorylation can trigger apoptosis. Little is
      known as to its effects on mesencephalic dopamine neurons, the major neurons lost
      in Parkinson's disease. In this study, okadaic acid (OKA), a phosphatase 1 and 2A
      inhibitor, with greater potency toward 2A, was toxic to mesencephalic dopamine
      and gamma-aminobutyric acid (GABA) neurons, however, dopamine neurons were 4-fold
      more sensitive. The EC(50) for dopamine versus GABA toxicity was 1.5 versus 6.5
      nM, respectively, and was consistent with an inhibition of phosphatase 2A.
      Dopamine neurons were also more sensitive to calyculin-A, a phosphatase inhibitor
      equipotent toward 1 and 2A. OKA-methyl-ester, which lacks phosphatase inhibitory
      activity, was without effect. DNA laddering typical of apoptosis was observed in
      cultures at a concentration that was specifically toxic to dopamine neurons (5
      nM). In contrast to the sensitivity of mesencephalic neurons to phosphatase
      inhibition, inhibition of protein kinase activity with staurosporine or K252a
      showed little toxicity and protected neurons from OKA. Consistent with in vitro
      findings, infusion of 32 to 320 pmol of OKA into the left striatum of rats caused
      a dose-dependent loss of striatal dopamine without any loss of GABA 1 week
      following infusion. Acutely, OKA increased tyrosine hydroxylase activity, a
      phosphatase 2A substrate, and increased dopamine turnover. The above-mentioned
      findings demonstrate that dysregulation of phosphatase activity is detrimental to
      mesencephalic neurons, with dopamine neurons, in vitro and in vivo, being
      relatively more sensitive to phosphatase 2A inhibition. Disturbances in the
      phosphorylation control of proteins unique to dopamine neurons may contribute to
      their enhanced vulnerability to OKA exposure.

PMID- 11504787
TI  - Antitumor activity of antisense clusterin oligonucleotides is improved in vitro
      and in vivo by incorporation of 2'-O-(2-methoxy)ethyl chemistry.
AB  - Phosphorothioate (P=S) antisense oligonucleotides (ASO) targeting the cell
      survival gene clusterin synergistically enhance castration- and chemotherapy
      induced apoptosis in prostate cancer xenografts. This study compares efficacy,
      tissue half-lives, and toxicity of P=S clusterin ASO to third-generation backbone
      2'-O-(2-methoxy)ethyl (2'MOE) ribose-modified clusterin ASO. Northern analysis
      quantified changes in clusterin mRNA levels in human PC-3 cells and tumors. The 3
      (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay measured effects
      of combined clusterin ASO plus paclitaxel on PC-3 cell growth. Athymic mice
      bearing PC-3 tumors were treated with paclitaxel plus either P=S clusterin ASO,
      2'-MOE clusterin ASO, or mismatch control oligonucleotides for 28 days. Weekly
      body weights and serum parameters were measured to assess toxicity. Tissue half
      life of P=S and 2'-MOE ASO in PC-3 tumors was assessed using capillary gel
      electrophoresis (CGE). Both 2'-MOE and P=S ASO decreased clusterin mRNA levels in
      a dose-dependent and sequence-specific manner. 2'-MOE ASO more potently
      suppressed clusterin mRNA (80 versus 40% at 500 nM) compared with P=S ASO. IC(50)
      of paclitaxel was equally reduced (50--75%) by both compounds. In vivo tissue
      half-life was significantly longer for 2'-MOE-modified ASO than for P=S ASO (5
      versus 0.5 days). Using CGE, >90% of detected 2'-MOE ASO in tumor tissue was full
      length. Weekly administration of 2'-MOE clusterin ASO was equivalent to daily P=S
      clusterin ASO in enhancing paclitaxel efficacy in vivo. 2'-MOE-modified ASO
      potently suppressed clusterin expression and prolonged tissue half-lives with no
      additional side effects. These results support the use of 2'-MOE-modified ASO
      over conventional P=S ASO by potentially increasing potency and allowing longer
      dosing intervals in clinical trials.

PMID- 11504788
TI  - Biphasic alterations of cAMP levels and inhibition of norepinephrine release in
      iris-ciliary body by bremazocine.
AB  - Kappa-opioid receptor agonists have been shown to reduce intraocular pressure in
      rabbits and monkeys. This study was designed to investigate mechanisms in the
      iris-ciliary body (ICB) that may be involved in bremazocine (BRE)-induced ocular
      hypotension in New Zealand White rabbits. Using ICBs, BRE and norbinaltorphimine
      (nor-BNI), relatively selective kappa-opioid receptor agonist and antagonist,
      respectively, along with pertussis toxin (PTX), were used to evaluate the effect
      of 1) kappa-opioid receptors on [(3)H]norepinephrine (NE) release from
      postganglionic sympathetic neurons, and 2) cAMP accumulation. BRE caused dose
      related (0.1, 1, and 10 microM) inhibition of electrically stimulated [(3)H]NE
      release from ICBs to 77, 57, and 36% of the control, respectively. Nor-BNI
      antagonized the inhibition of [(3)H]NE release by BRE, while PTX pretreatment
      limited the suppressive effect of BRE (1 and 10 microM). When used alone, BRE
      (0.01, 0.1, 1, and 10 microM) caused stimulation of cAMP levels in ICBs, however,
      similar concentrations caused inhibition of isoproterenol (ISO)-stimulated cAMP
      production. Pretreatment of ICBs with nor-BNI (10 microM) or PTX (150 ng/ml)
      antagonized BRE-induced suppression of ISO-stimulated cAMP. These data
      demonstrate that BRE acts at multiple [prejunctional (neuronal) and
      postjunctional] sites in the ICB. BRE had a biphasic effect on ISO-stimulated
      adenylyl cyclase activity; enhancing cAMP levels at low concentrations and
      inhibiting cAMP production at high concentrations. Based on the modifications
      induced by PTX pretreatment, the kappa-opioid receptors involved in some of the
      ocular actions of BRE are linked to a G(i/o) protein.

PMID- 11504789
TI  - Transport characteristics of the anti-human immunodeficiency virus nucleoside
      analog, abacavir, into brain and cerebrospinal fluid.
AB  - The role of the blood-brain and blood-cerebrospinal fluid (CSF) barriers in the
      distribution of anti-human immunodeficiency virus (HIV) drugs is integral to the
      design of effective treatment regimens for HIV infection within the brain.
      Abacavir (formerly 1592U89) is a nucleoside analog reverse transcriptase
      inhibitor, which has activity against HIV. The ability of this drug to reach the
      brain at therapeutic concentrations has been explored by means of an established
      bilateral in situ brain perfusion model in combination with high-performance
      liquid chromatography analysis in the anesthetized guinea pig. The influence of
      other drugs on the entry of abacavir into the brain was also investigated and is
      of special significance with the use of three of more anti-HIV drugs as the
      recommended treatment for HIV infection. The results of this study indicate that
      intact [(14)C]abacavir can cross the blood-brain and blood-CSF barriers and enter
      the brain and cisternal CSF. Further studies, at a perfusion time of 10 min,
      revealed that the uptake (R(cerebrum)) of this (14)C-labeled drug (10.1 +/- 0.6%)
      was not affected by the presence of 0.86 to 200 microM unlabeled abacavir (6.8
      microM; 11.0 +/- 1.4%), the nucleoside transport inhibitor [10 microM 6-(4
      nitrobenzyl)thio-9-beta-D-ribofuranosylpurine; 9.7 +/- 3.3%], or a substrate for
      the nucleobase transporter (100 microM adenine; 12.7 +/- 3.0%). This would
      suggest that the entry of abacavir into the brain would not be affected by the
      presence of other anti-HIV drugs. The results of this animal study indicate that
      abacavir would be a useful addition to a treatment regimen against HIV-infection
      within the brain.

PMID- 11504790
TI  - In contrast to forskolin and 3-isobutyl-1-methylxanthine, amrinone stimulates the
      cardiac voltage-sensitive release mechanism without increasing calcium-induced
      calcium release.
AB  - The objective of this study was to determine whether the voltage-sensitive
      release mechanism (VSRM) can be stimulated independently from Ca(2+)-induced
      Ca(2+) release (CICR) by drugs that elevate intracellular cAMP. Contractions were
      measured in voltage-clamped guinea pig ventricular myocytes at 37 degrees C.
      Na(+) current was blocked. We compared effects of agents that elevate cAMP
      through activation of adenylyl cyclase (1 microM forskolin), nonspecific
      inhibition of phosphodiesterases (PDEs) [100 microM 3-isobutyl-1-methylxanthine
      (IBMX)], and selective inhibition of PDE III (100-500 microM amrinone) on
      contractions initiated by the VSRM and CICR. Forskolin and IBMX significantly
      increased peak Ca(2+) current and CICR. In addition, these agents also markedly
      increased contractions elicited by test steps from -65 to -40 mV, which activate
      the VSRM. However, because these steps also induced inward current in the
      presence of forskolin or IBMX, CICR could not be excluded. In contrast, amrinone
      caused a large, concentration-dependent increase in VSRM contractions but had no
      effect on CICR contractions or Ca(2+) current. Sarcoplasmic reticulum Ca(2+),
      assessed by rapid application of caffeine (10 mM), was increased only modestly by
      all three drugs. Normalization of contractions to caffeine contractures indicated
      that amrinone increased fractional release by the VSRM, but not CICR. Forskolin
      and IBMX increased fractional release elicited by steps to -40 mV. Increases in
      CICR induced by forskolin and IBMX were proportional to caffeine contractures.
      Thus, positive inotropic effects of cAMP on VSRM contractions may be
      compartmentalized separately from effects on Ca(2+) current and CICR.

PMID- 11504791
TI  - Dosing time-dependent tolerance of catalepsy by repetitive administration of
      haloperidol in mice.
AB  - To investigate the effect of repeated administration time on the development of
      tolerance, male ICR mice, housed under 12:12-h light/dark cycle (7:00 AM, lights
      on), were treated with haloperidol 4 mg/kg/day i.p. at 9:00 AM or 9:00 PM, the
      time nearly corresponding to the maximal or minimal catalepsy responses to a
      single dose, respectively, for 14 days and catalepsy responses were monitored at
      1 h after administration each day. The findings indicated that, on day 1 to day
      6, a greater development of tolerance was seen in the group of mice treated at
      9:00 AM, and catalepsy behavior exhibited a significant difference between the
      two dosing times (P < 0.01). The study of D(2) receptor mRNA expression in mouse
      striatum revealed that the phase of D(2) receptor mRNA rhythm was similar to that
      of catalepsy response, with the maximum around mid-light and the minimum around
      mid-dark. After repeated administration, the increase in D(2) receptor mRNA
      levels in mice treated with haloperidol at 9:00 AM was higher than that of mice
      treated with haloperidol at 9:00 PM. In addition, from a [(3)H]spiperone binding
      study, the amount of binding site [(3)H]spiperone after repeated injection of
      haloperidol at 9:00 AM was greater than that after repeated injection at 9:00 PM.
      These findings demonstrate the importance of dosing time on the susceptibility to
      extrapyramidal effects and the relation of administration time to D(2) receptor
      change and tolerance.

PMID- 11504792
TI  - Inhibitors of bradykinin-inactivating enzymes decrease myocardial
      ischemia/reperfusion injury following 3 and 7 days of reperfusion.
AB  - Inhibitors of bradykinin (BK)-inactivating enzymes protect from myocardial
      ischemia/reperfusion injury after short periods of reperfusion. However,
      protection after 2 to 3 h of reperfusion does not mean that myocardium remains
      viable for an extended time. Therefore, we examined the effects of inhibitors of
      angiotensin-converting enzyme (ramiprilat), EP24.11 (cFP-F-pAB), and EP24.15 (cFP
      AAF-pAB) in a chronic model of myocardial ischemia/reperfusion injury. A left
      descending coronary artery was occluded for 30 min in anesthetized rabbits.
      Saline, ramiprilat, or endopeptidase inhibitors were given after 27 min of
      occlusion. The BK(2) receptor antagonist HOE140 was administered in certain
      experiments. After ischemia, the occlusion was released, and the animal allowed
      to recover for 3 or 7 days. Surgery was then repeated, and the heart removed for
      determination of infarct size. In separate experiments, the heart was removed
      after 2 h of reperfusion for determination of BK tissue levels. Ramiprilat and
      endopeptidase inhibitors reduced infarct size at 3 and 7 days. Combining
      inhibitors further reduced infarct size after 3 days. The protective effect of
      the endopeptidase inhibitors was blocked by HOE140. Infarct sizes at 7 days were
      larger than at 3 days. The additive effect of multiple inhibitors was absent at 7
      days. Ramiprilat and cFP-F-pAB significantly increased tissue BK levels. We
      conclude that inhibition of BK-inactivating enzymes protects endogenous BK from
      degradation and provides long-lasting protection from myocardial
      ischemia/reperfusion injury. A single treatment at the time of reperfusion does
      not prevent extension of the infarction between 3 and 7 days.

PMID- 11504793
TI  - Cell cycle effects of nonsteroidal anti-inflammatory drugs and enhanced growth
      inhibition in combination with gemcitabine in pancreatic carcinoma cells.
AB  - Increased cyclooxygenase-2 (COX-2) expression in human pancreatic
      adenocarcinomas, as well as the growth-inhibitory effect of nonsteroidal anti
      inflammatory drugs (NSAIDs) in vitro, suggests that NSAIDs may be an effective
      treatment for pancreatic cancer. Gemcitabine is currently the most effective
      chemotherapeutic drug available for patients with pancreatic cancer, but is only
      minimally effective against this aggressive disease. Clearly, other treatment
      options must be identified. To design successful therapeutic strategies involving
      compounds either alone or in combination with others, it is necessary to
      understand their mechanism of action. In the present study, we evaluated the
      effects of three NSAIDs (sulindac, indomethacin, and NS-398) or gemcitabine in
      two human pancreatic carcinoma cell lines, BxPC-3 (COX-2-positive) and PaCa-2
      (COX-2-negative), previously shown to be growth-inhibited by these NSAIDs.
      Effects on cell cycle and apoptosis were investigated by flow cytometry or
      Western blotting. Treatment with NSAIDs or gemcitabine altered the cell cycle
      phase distribution as well as the expression of multiple cell cycle regulatory
      proteins in both cell lines, but did not induce substantial levels of apoptosis.
      Furthermore, we demonstrated that the combination of the NSAID sulindac or NS-398
      with gemcitabine inhibited cell growth to a greater degree than either compound
      alone. These results indicate that the antiproliferative effects of NSAIDs and
      gemcitabine in pancreatic tumor cells are primarily due to inhibition of cell
      cycle progression rather than direct induction of apoptotic cell death,
      regardless of COX-2 expression. In addition, NSAIDs in combination with
      gemcitabine may hold promise in the clinic for the treatment of pancreatic
      cancer.

PMID- 11504794
TI  - Pentylenetetrazole-induced inhibition of recombinant gamma-aminobutyric acid type
      A (GABA(A)) receptors: mechanism and site of action.
AB  - Pentylenetetrazole (PTZ) is a central nervous system convulsant that is thought,
      based on binding studies, to act at the picrotoxin (PTX) site of the gamma
      aminobutyric acid type A (GABA(A)) receptor. In the present study, we have
      investigated the mechanism and site of action of PTZ in recombinant GABA(A)
      receptors. In rat alpha 1 beta 2 gamma 2 receptors, PTZ inhibited GABA-activated
      Cl(-) current in a concentration-dependent, voltage-independent manner, with an
      IC(50) of 0.62 +/- 0.13 mM. The mechanism of inhibition appeared competitive with
      respect to GABA in both rat and human alpha 1 beta 2 gamma 2 receptors. Varying
      subunit configuration (change or lack of alpha subunit isoform or lack of gamma 2
      subunit) had modest effects on PTZ-induced inhibition, as evidenced by comparable
      IC(50) values (0.6-2.2 mM) in all receptor configurations tested. This contrasts
      with PTX and other PTX-site ligands, which have greater affinity in receptors
      lacking an alpha subunit. Using a one-site model for PTZ interaction with alpha 1
      beta 2 gamma 2 receptors, the association rate (k(+1)) was found to be 1.14 x
      10(3) M(-1) s(-1) and the dissociation rate (k(-1)) was 0.476 s(-1), producing a
      functional k(d) of 0.418 mM. PTZ could only gain access to its binding site
      extracellularly. Single-channel recordings demonstrated that PTZ decreased open
      probability by increasing the duration of closed states but had no effect on
      single-channel conductance or open state duration. alpha-Isopropyl-alpha-methyl
      gamma-butyrolactone, a compound known to antagonize effects of PTX, also
      diminished the effects of PTZ. Taken together, our results indicate that
      pentylenetetrazole and picrotoxin interact with overlapping but distinct domains
      of the GABA(A) receptor.

PMID- 11504795
TI  - Mistletoe lectin-1 increases tumor necrosis factor-alpha release in
      lipopolysaccharide-stimulated whole blood via inhibition of interleukin-10
      production.
AB  - We examined the immunomodulatory properties of the mistletoe preparation Lektinol
      (standardized for mistletoe lectin-1) and recombinant mistletoe lectin-1 (rML-1)
      in vitro by assessing alterations in the cytokine response of human whole blood.
      Lektinol or rML-1 alone did not induce any cytokine release in unstimulated whole
      blood. However, the lipopolysaccharide (LPS)-induced release of tumor necrosis
      factor (TNF)-alpha was increased, and the secretion of interleukin (IL)-10 was
      reduced by Lektinol at a mistletoe lectin-1 (ML-1) concentration of 0.5 to 5
      ng/ml, whereas the LPS-induced secretion of IL-1 beta, IL-6, IL-12, and
      interferon-gamma was not affected. Lektinol did not alter the initial phase of
      TNF-alpha production but sustained TNF-alpha levels longer than in the LPS
      controls. Recombinant ML-1, but not the recombinant B-chain alone, also increased
      TNF-alpha release and decreased IL-10 release. We propose that the increase in
      TNF-alpha release is due to a specific inhibition of IL-10 release by Lektinol.
      This conclusion is based on the observation that blocking of endogenously formed
      IL-10 by a neutralizing antibody results in a similar increase of TNF-alpha in
      the late production phase after LPS stimulation. This hypothesis was also
      corroborated by the finding that when endogenously formed IL-10 was blocked,
      Lektinol could no longer increase TNF-alpha release. These results indicate that
      Lektinol modulates the cytokine response of human whole blood to LPS in a
      proinflammatory fashion, which can be attributed to ML-1.

PMID- 11504796
TI  - Dopamine inhibits vasopressin action in the rat inner medullary collecting duct
      via alpha(2)-adrenoceptors.
AB  - We compared the effects of dopamine and norepinephrine on vasopressin (AVP)
      stimulated increases in osmotic water permeability (Pf) and cAMP accumulation in
      the rat inner medullary collecting duct (IMCD). Both dopamine and norepinephrine
      inhibited AVP-induced Pf and cAMP accumulation in a concentration-dependent
      manner; however, norepinephrine was approximately 100-fold more potent than
      dopamine. The effects of dopamine on Pf were antagonized by the selective
      alpha(2)-adrenoceptor antagonist, rauwolscine (10 nM--1 microM). Clozapine (10
      microM), a dopamine D(4) receptor antagonist with significant activity at
      adrenergic receptors, partially attenuated both dopamine and norepinephrine
      induced decreases in AVP-stimulated Pf. Dopamine-induced inhibition of AVP
      dependent cAMP levels was antagonized by the alpha(2)-adrenoceptor antagonists,
      rauwolscine, idazoxan, and yohimbine, but not by the dopamine receptor
      antagonists, spiperone, SCH-23390, or raclopride. Clozapine (1--10 microM)
      inhibited the effects of both dopamine and norepinephrine on AVP-stimulated cAMP
      levels. We conclude that the inhibitory effects of dopamine on AVP-induced Pf and
      cAMP accumulation in the rat IMCD are mediated via alpha(2)-adrenoceptors.

PMID- 11504797
TI  - Opioid and cannabinoid modulation of precipitated withdrawal in delta(9)
      tetrahydrocannabinol and morphine-dependent mice.
AB  - The goal of the present study was to elucidate the relationship between
      cannabinoid and opioid systems in drug dependence. The CB(1) cannabinoid receptor
      antagonist SR 141716A precipitated both paw tremors and head shakes in four
      different mouse strains that were treated repeatedly with Delta(9)
      tetrahydrocannabinol (Delta(9)-THC). SR 141716A-precipitated Delta(9)-THC
      withdrawal was ameliorated in mu-opioid receptor knockout mice compared with the
      wild-type control animals and failed to occur in mice devoid of CB(1) cannabinoid
      receptors. An acute injection of morphine in Delta(9)-THC-dependent mice
      undergoing SR 1417161A-precipitated withdrawal dose dependently decreased both
      paw tremors, antagonist dose 50 (AD(50)) (95% CL) = 0.035 (0.03--0.04), and head
      shakes, AD(50) (95% CL) = 0.07 (0.04--0.12). In morphine-dependent mice, the
      opioid antagonist naloxone precipitated head shakes, paw tremors, diarrhea, and
      jumping. As previously reported, naloxone-precipitated morphine withdrawal failed
      to occur in mu-opioid knockout mice and was significantly decreased in CB(1)
      cannabinoid receptor knockout mice. Acute treatment of Delta(9)-THC in morphine
      dependent mice undergoing naloxone-precipitated withdrawal blocked paw tremors,
      AD(50) (95% CL) = 0.5 (0.3--1.0), and head shakes AD(50) (95% CL) = 0.6 (0.57-
      0.74) in dose-dependent manners, but failed to diminish the occurrence of
      diarrhea or jumping. Finally, naloxone and SR 141716A failed to elicit any overt
      effects in Delta(9)-THC-dependent and morphine-dependent mice, respectively.
      These findings taken together indicate that the mu-opioid receptor plays a
      modulatory role in cannabinoid dependence, thus implicating a reciprocal
      relationship between the cannabinoid and opioid systems in dependence.

PMID- 11504798
TI  - Agonist-, antagonist-, and inverse agonist-regulated trafficking of the delta
      opioid receptor correlates with, but does not require, G protein activation.
AB  - In this study, we explored the relationship between ligand-induced regulation of
      surface delta opioid receptors and G protein activation. G protein activation was
      assessed with [(35)S]guanosine-5'-O-(3-thio)triphosphate (GTP gamma S) binding
      assays conducted at both 37 and 0 degrees C. Ligand-independent (constitutive)
      activity of the delta-receptor was readily observed when the [(35)S]GTP gamma S
      binding assay was performed at 37 degrees C. We identified a new class of
      alkaloid inverse agonists (RTI-5989-1, RTI-5989-23, RTI-5989-25), which are more
      potent than the previously described peptide inverse agonist ICI-174864 (N,N
      diallyl-Tyr-Aib-Aib-Phe-Leu). Treatment with these inverse agonists for 18 h
      caused up-regulation of surface receptors. Eighteen-hour treatment with etorphine
      resulted in approximately 90% loss of surface receptor, whereas fentanyl,
      diprenorphine, and morphine caused between 20 and 50% loss. The abilities of
      ligands to modulate [(35)S]GTP gamma S binding at 37 degrees C showed a strong
      correlation with their abilities to regulate surface receptor number (r(2) =
      0.86). Interestingly, the ability of fentanyl to activate G proteins was markedly
      temperature sensitive. Fentanyl showed no stimulation of [(35)S]GTP gamma S
      binding at 0 degrees C but was as efficacious as etorphine, morphine, and
      diprenorphine at 37 degrees C. Neither the ligand-induced receptor increases nor
      decreases were perturbed by pertussis toxin pretreatment, suggesting that
      functional G proteins are not required for ligand-regulated delta-opioid receptor
      trafficking.

PMID- 11504799
TI  - Metabolism of methadone and levo-alpha-acetylmethadol (LAAM) by human intestinal
      cytochrome P450 3A4 (CYP3A4): potential contribution of intestinal metabolism to
      presystemic clearance and bioactivation.
AB  - Methadone and levo-alpha-acetylmethadol (LAAM) are opioid agonists used for
      analgesia and preventing opiate withdrawal. Methadone is sequentially N
      demethylated to the inactive metabolites 2-ethylidene-1,5-dimethyl-3,3
      diphenylpyrrolidine (EDDP) and 2-ethyl-5-methyl-3,3-diphenylpyraline (EMDP). LAAM
      is essentially a prodrug that undergoes bioactivation via sequential N
      demethylation to levo-alpha-acetyl-N-normethadol (nor-LAAM) and levo-alpha-acetyl
      N,N-dinormethadol (dinor-LAAM). Methadone and LAAM are metabolized by CYP3A4 in
      human liver. Since they are administered orally, and CYP3A4 is expressed in human
      intestine, we tested the hypotheses that human intestine can metabolize methadone
      and LAAM, and evaluated the participation of CYP3A4. Intestinal microsomal
      methadone N-demethylation exhibited hyperbolic noncooperative kinetics and
      biphasic Eadie-Hofstee plots. Using a dual-enzyme Michaelis-Menten model, K(m)
      values were 11 and 1200 microM for EDDP and 23 and 930 microM for EMDP formation,
      respectively. CYP3A4 inhibitors (troleandomycin and ketoconazole) inhibited EDDP
      and EMDP formation by >70%. Methadone N-demethylation by CYP3A4 showed biphasic
      Eadie-Hofstee plots without evidence of positive cooperativity; K(m) values were
      10 and 1100 microM for EDDP and 20 and 1000 microM for EMDP formation. Intestinal
      microsomal LAAM and nor-LAAM N-demethylation also exhibited hyperbolic kinetics
      and biphasic Eadie-Hofstee plots. K(m) values were 21 and 980 microM for nor-LAAM
      from LAAM and 18 and 1200 microM for dinor-LAAM from nor-LAAM. Troleandomycin and
      ketoconazole inhibited N-demethylation by >70%. LAAM and nor-LAAM metabolism by
      CYP3A4 showed biphasic Eadie-Hofstee plots without evidence of positive
      cooperativity; K(m) values were 8 and 1300 microM, 6 and 950 microM,
      respectively. Predicted in vivo intestinal extraction of methadone and LAAM is 21
      and 33%, respectively. We conclude that methadone, LAAM, and nor-LAAM are
      metabolized by human intestinal microsomes; CYP3A4 is the predominant cytochrome
      P450 isoform; CYP3A4-catalyzed methadone, LAAM, and nor-LAAM metabolism is
      characterized by noncooperative, multisite kinetics; and intestinal metabolism
      may contribute to presystemic methadone inactivation and LAAM bioactivation.

PMID- 11504800
TI  - Fenamates: a novel class of reversible gap junction blockers.
AB  - The effect of fenamates on gap junctional intercellular communication was
      investigated in monolayers of normal rat kidney (NRK) fibroblasts and of SKHep1
      cells overexpressing the gap junction protein connexin43 (Cx43). Using two
      different methods to study gap junctional intercellular communication, single
      electrode voltage-clamp step response measurements and dye microinjection, we
      show that fenamates are reversible blockers of Cx43-mediated intercellular
      communication. After adding fenamates to a confluent monolayer of electrically
      coupled NRK fibroblasts, the voltage step-induced capacitive current transient
      changed from a transient characteristic for charging multiple coupled cell
      capacitances to one characteristic for a single cell in isolation. The
      capacitance of completely uncoupled cells was 19.7 +/- 1.0 pF (mean +/- S.E.M.; n
      = 11). Junctional conductance between the patched cell and the surrounding cells
      in the monolayer changed from >140.7 +/- 9.6 nS (mean +/- S.E.M.; n = 14) to <1.4
      +/- 0.4 nS (mean +/- S.E.M.; n = 11) after uncoupling. Electrical coupling could
      be restored to >51.8 +/- 4.2 nS (mean +/- S.E.M.; n = 11) by washout of the
      fenamates. Voltage-clamp step response measurements showed that the potency of
      fenamates in inhibiting electrical coupling decreases in the order meclofenamic
      acid > niflumic acid > flufenamic acid. The half-maximal concentration determined
      by dye-coupling experiments was 25 and 40 microM for meclofenamic acid and
      flufenamic acid, respectively. Inhibition of gap junctional communication by
      fenamates did not involve changes in intracellular calcium or pH, and was
      unrelated to protein kinase C activity or an inhibition of cyclooxygenase
      activity. Voltage-clamp step response measurements in confluent monolayers of
      SKHep1 cells that had been stably transfected with Cx43 revealed that fenamates
      are potent blockers of Cx43-mediated intercellular communication. In conclusion,
      fenamates represent a novel class of reversible gap junction blockers that can be
      used to study the role of Cx43-mediated gap junctional intercellular
      communication in biological processes.

PMID- 11504801
TI  - Alpha(1) and beta(2) adrenoreceptor agonists inhibit pentylenetetrazole-induced
      seizures in mice lacking norepinephrine.
AB  - It has been known for many years that norepinephrine (NE) is a potent endogenous
      anticonvulsant, yet there is confusion as to which receptor(s) mediate this
      effect. This is probably due to multiple factors, including the importance of
      distinct signaling pathways for different seizure paradigms, a lack of
      comprehensive pharmacological studies, and difficulty in interpreting existing
      pharmacological results due to the presence of endogenous NE. We sought to
      circumvent these problems by testing the anticonvulsant activity of selective
      agonists for most known adrenoreceptors (ARs) in dopamine beta-hydroxylase
      knockout (Dbh -/-) mice that lack endogenous NE. Dbh -/- mice are hypersensitive
      to pentylenetetrazole (PTZ)-induced seizures, demonstrating that endogenous NE
      inhibits PTZ-induced seizures in the wild type. Pretreatment of Dbh -/- mice with
      an alpha(1)AR or beta(2)AR, but not an alpha(2)AR or beta(1)AR agonist
      significantly protected against PTZ-induced seizures. In contrast, only the
      beta(2)AR agonist showed anticonvulsant activity in heterozygous controls.
      Furthermore, an alpha(1)AR antagonist exacerbated PTZ-induced seizures in control
      mice, whereas a beta(2)AR antagonist had no effect. We conclude that activation
      of the alpha(1)AR is primarily responsible for the anticonvulsant activity of
      endogenous NE in the murine PTZ model of epilepsy. Endogenous NE probably does
      not activate the beta(2)AR under these conditions, but exogenous activation of
      the beta(2)AR produces an anticonvulsant effect.

PMID- 11504802
TI  - GR89,696: a potent kappa-opioid agonist with subtype selectivity in rhesus
      monkeys.
AB  - GR89,696 is a synthetic kappa-opioid receptor agonist, recently reported to have
      an agonist profile consistent with selectivity at the proposed "kappa(2)"
      subtype. The present studies evaluated the effects of GR89,696 in vitro (i.e., in
      radioligand binding and [(35)S]guanosine-5'-O-(3-thio)triphosphate assays) and in
      vivo in rhesus monkeys, in assays used to study kappa-opioid agonists (i.e.,
      thermal antinociception, sedation and muscle relaxation, diuresis, and increases
      in serum prolactin levels, as well as ethylketocyclazocine and U69,593
      discrimination). Furthermore, the sensitivity of GR89,696 to naltrexone and nor
      binaltorphimine (nor-BNI) antagonism was compared with that of U50,488 and
      U69,593, ligands selective for the proposed "kappa(1)" subtype. Overall, GR89,696
      displayed the profile of a highly potent kappa-opioid agonist, following
      parenteral administration in rhesus monkeys. GR89,696 was less sensitive than
      U50,488 and U69,593 to naltrexone or nor-BNI antagonism, consistent with an
      action through the proposed kappa(2) receptor subtype.

PMID- 11504803
TI  - Decrease in Ca(2+)-sensitizing effect of UD-CG 212 Cl, a metabolite of
      pimobendan, under acidotic condition in canine ventricular myocardium.
AB  - We studied the influence of acidosis on the positive inotropic effect of UD-CG
      212 Cl (4,5-dihydro-6-[2-(4-hydroxyphenyl)-1H-benzimidazole-5-yl]-5-methyl-3(2H)
      pyridazinone), an active metabolite of pimobendan, in canine ventricular
      trabeculae loaded with aequorin. The positive inotropic effect of UD-CG 212 Cl
      was markedly suppressed under acidotic conditions. The maximal contractile
      response to UD-CG 212 Cl was attained at 10(-5) M in the control condition at pH
      7.4, but was not achieved even at 10(-4) M during acidosis. The maximal inotropic
      effect of UD-CG 212 Cl was 18% of the maximal response to isoproterenol
      (ISO(max)) in association with an increase in Ca(2+) transients of 7% of ISO(max)
      in the control, while they are 8 and 6% of ISO(max) under acidosis, respectively.
      Acidosis abolished the increase in myofilament Ca(2+) sensitivity induced by UD
      CG 212 Cl, whereas the increase in Ca(2+) transients induced by the compound was
      not affected by acidosis. In conclusion, UD-CG 212 Cl elicited a positive
      inotropic effect even under acidosis, however, UD-CG 212 Cl was much less
      effective as a cardiotonic agent under acidosis mainly due to a decrease in the
      Ca(2+)-sensitizing effect under acidotic condition.

PMID- 11504804
TI  - Actions of pyrethroid insecticides on sodium currents, action potentials, and
      contractile rhythm in isolated mammalian ventricular myocytes and perfused
      hearts.
AB  - Pyrethroid insecticides are known to modify neuronal sodium channels, inducing
      persistent, steady-state sodium current at depolarized membrane potentials.
      Cardiac myocytes are also rich in sodium channels but comparatively little is
      known about the effect of pyrethroids on the heart, or on the cardiac sodium
      channel isoform. In the present study therefore, we determined the actions of
      type I and type II pyrethroids against rat and guinea pig ventricular myocytes
      under current and voltage clamp, and on isolated perfused rat hearts. In
      myocytes, tefluthrin (type I) and fenpropathrin and alpha-cypermethrin (type II)
      prolonged action potentials and evoked afterdepolarizations. The time course of
      sodium current (I(Na)) was also prolonged by these compounds. Pyrethroids delayed
      I(Na) inactivation, when measured under selective conditions as current sensitive
      to 30 microM tetrodotoxin, by increasing the proportion of slowly inactivating
      current at the expense of fast inactivating current. Further experiments,
      focusing on fenpropathrin, revealed that its effects on I(Na) inactivation time
      course were dose-dependent, and the Na(+) "window-current" was increased in its
      presence. In unstimulated, isolated hearts perfused with the same pyrethroids,
      the variability in contraction amplitude increased due to variations in the
      intervals between heartbeats. These potentially arrhythmogenic changes are
      consistent with the effects observed at the cellular level. The type I pyrethroid
      tetramethrin had little effect in any of the preparations. These findings suggest
      that some pyrethroids possess considerable mammalian cardiac arrhythmogenic
      potential, the manifestation of which in vivo may depend on the route of
      exposure.

PMID- 11504805
TI  - Genetic regulation of extracellular serotonin by 5-hydroxytryptamine(1A) and 5
      hydroxytryptamine(1B) autoreceptors in different brain regions of the mouse.
AB  - The regulation of extracellular levels of 5-hydroxytryptamine (serotonin) (5-HT)
      in the striatum and ventral hippocampus was studied using in vivo microdialysis
      in awake, unrestrained wild-type 5-HT(1A) and 5-HT(1B) receptor knockout mice.
      Systemic administration of the selective serotonin reuptake inhibitor fluoxetine
      evoked a significant dose-dependent increase in extracellular 5-HT in both the
      striatum and hippocampus at both 2.5 mg/kg (i.p.) and 20 mg/kg (i.p.) in wild
      type mice. In 5-HT(1A) receptor knockout mice, the response to 2.5 mg/kg
      fluoxetine was significantly augmented in the striatum but not the hippocampus,
      whereas the response to 20 mg/kg fluoxetine was significantly greater in both
      brain regions. In 5-HT(1B) receptor knockout mice, the increase of extracellular
      5-HT was augmented in the hippocampus but not the striatum at both doses of
      fluoxetine. The response pattern to fluoxetine alone in 5-HT receptor mutant mice
      corresponded with the effects of fluoxetine given with either the 5-HT(1A)
      receptor antagonist WAY 100635 (0.1 mg/kg i.p.) or the 5-HT(1B/1D) receptor
      antagonist GR 127935 (0.056 mg/kg) in wild-type mice. These results indicate
      common topographical regulation of 5-HT release in different brain regions by
      genetic mutation and pharmacological challenges. The 5-HT(1A) autoreceptor plays
      a larger role in regulating 5-HT release in the striatum and possibly other brain
      regions innervated by the dorsal raphe nucleus, whereas the role of the 5-HT(1B)
      receptor is relatively greater in the hippocampus and possibly other brain
      regions innervated by the median raphe nucleus.

PMID- 11504806
TI  - Regional patterns of compensation following genetic deletion of either 5
      hydroxytryptamine(1A) or 5-hydroxytryptamine(1B) receptor in the mouse.
AB  - Plasticity in serotonergic transmission in serotonin or 5-hydroxytryptamine (5
      HT) receptor mutants was examined by measuring the regulation of extracellular 5
      HT levels in the striatum and ventral hippocampus of 5-HT(1A) and 5-HT(1B)
      receptor knockout mice using in vivo microdialysis. The efficacy of genetic
      deletion was verified by showing blunted regulation of extracellular 5-HT with
      selective 5-HT receptor agonists. 5-HT(1A) receptor knockout mice failed to
      demonstrate reduction of extracellular 5-HT in response to systemic
      administration of the 5-HT(1A) receptor agonist R-8-hydroxydipropylaminotetralin
      (R-8-OH-DPAT) and 5-HT(1B) receptor knockout mice failed to demonstrate reduction
      of extracellular 5-HT in response to systemic administration of the 5-HT(1B)
      receptor agonist CP 94,253. Plasticity also developed to deletion of the
      complementary autoreceptor. 5-HT(1A) receptor knockout mice demonstrated a
      significantly greater response to CP 94,253 in the striatum, but not the ventral
      hippocampus, suggesting the development of enhanced sensitivity of striatal 5
      HT(1B) receptors. In 5-HT(1B) receptor knockout mice, R-8-OH-DPAT evoked a
      significantly diminished response in the ventral hippocampus, but not the
      striatum, suggesting the potential desensitization of 5-HT(1A) receptors in the
      median raphe nucleus. The pattern of regional compensations between
      somatodendritic and terminal autoreceptors was confirmed by pharmacological
      challenges using the selective serotonin reuptake inhibitor fluoxetine combined
      with either a 5-HT(1A) (WAY 100635) or a 5-HT(1B/1D) (GR 127935) receptor
      antagonist. The regional pattern of compensation may be determined by the
      preferential role of 5-HT(1A) or 5-HT(1B) receptors in regulating 5-HT release.
      Taken together, these results demonstrate the development of regional plasticity
      between complementary somatodendritic and terminal autoreceptors after the
      genetic deletion of 5-HT(1A) or 5-HT(1B) receptors.

PMID- 11504807
TI  - Antidepressant-like behavioral effects in 5-hydroxytryptamine(1A) and 5
      hydroxytryptamine(1B) receptor mutant mice.
AB  - The development of serotonin receptor knockout mice has provided an opportunity
      to study antidepressant drug effects in animals with targeted genetic deletion of
      receptors involved in antidepressant responses. In the current study, the effects
      of two types of antidepressant drugs, the selective serotonin reuptake inhibitors
      fluoxetine and paroxetine and the selective norepinephrine reuptake inhibitor
      desipramine, were examined in 5-hydroxytryptamine (5-HT)(1A) and 5-HT(1B)
      receptor mutant mice using the tail suspension test (TST). Under baseline
      conditions, the immobility of 5-HT(1A) receptor mutant mice, but not 5-HT(1B)
      receptor mutant mice, was significantly lower than that of wild-type mice. The
      decreased baseline immobility in 5-HT(1A) receptor mutant mice was reversed by
      pretreatment with alpha-methyl-para-tyrosine, but not by para
      chlorophenylalanine, suggesting mediation by enhanced catecholamine function. In
      wild-type mice, fluoxetine (10.0--20.0 mg/kg i.p.) and desipramine (5.0--20.0
      mg/kg i.p.) both significantly decreased immobility in the TST. In 5-HT(1A)
      receptor mutant mice, desipramine (20.0 mg/kg i.p.) significantly decreased
      immobility, whereas fluoxetine (20.0 mg/kg i.p.) and paroxetine (20.0 mg/kg i.p.)
      had no effect. The immobility of 5-HT(1B) receptor mutant mice was decreased
      similarly by desipramine (5.0--20.0 mg/kg i.p.). However, the effect of low doses
      of fluoxetine were significantly augmented in the 5-HT(1B) receptor mutant mice
      (2.5--20.0 mg/kg i.p.) compared with wild-type mice. Administration of selective
      5-HT receptor antagonists in wild-type mice partially reproduced the phenotypes
      of the mutant mice. These results suggest that 5-HT(1A) and 5-HT(1B) receptors
      have different roles in the modulation of the response to antidepressant drugs in
      the TST.

PMID- 11504808
TI  - Effects of anorexinogen agents on cloned voltage-gated K(+) channel hKv1.5.
AB  - Appetite suppressants have been associated with primary pulmonary hypertension
      (PPH), inhibition of voltage-gated potassium channels, membrane depolarization,
      and calcium entry in pulmonary artery smooth muscle cells. In cells taken from
      pulmonary arteries of primary pulmonary hypertensive patients, voltage-gated
      potassium channels appear to be dysfunctional and in particular, reduced hKv1.5
      gene transcription and hKv1.5 mRNA instability have been shown. We have compared
      the effects of anorexinogen agents on hKv1.5 channels stably expressed in
      mammalian cell line. We found that aminorex, phentermine, dexfenfluramine,
      sibutramine, and fluoxetine cause a dose-dependent inhibition of hKv1.5 current.
      Aminorex, phentermine, and dexfenfluramine had a K(D) of inhibition greater than
      to 300 microM and are not potent inhibitors of hKv1.5. Sibutramine and fluoxetine
      inhibited hKv1.5 current with lower K(D) values of 41 and 21 microM,
      respectively. Block by both drugs increased rapidly between -20 and +10 mV,
      coincident with channel opening and suggested an open channel block mechanism.
      This was confirmed by a slower deactivation time course resulting in a
      "crossover" phenomenon when tail currents recorded under control conditions and
      in the presence of either drug were superimposed. Single channel experiments
      demonstrated that open probability and open duration of hKv1.5 were decreased by
      fluoxetine and sibutramine. These results indicate that among the anorexinogen
      agents tested, sibutramine and fluoxetine are the most potent toward hKv1.5
      channel, which they preferentially block in the open state. Nevertheless, their
      inhibitory effects do not correlate with their ability to produce PPH neither
      with their previously reported therapeutic plasma concentrations.

PMID- 11504809
TI  - Effect of steviol on para-aminohippurate transport by isolated perfused rabbit
      renal proximal tubule.
AB  - An inhibitory effect of steviol, metabolite of the natural sweetener stevioside,
      on transepithelial transport of p-aminohippurate (J(PAH)) was observed in
      isolated S(2) segments of rabbit renal proximal tubules using in vitro
      microperfusion. Addition of steviol (0.01--0.25 mM) to the bathing medium
      significantly depressed J(PAH) (approximately 50--90%). This inhibitory effect
      was dose-dependent and was maximum at a concentration of 0.05 mM. To further
      examine this effect, a steviol concentration (0.01 mM) that produced
      approximately 50% inhibition of J(PAH), was chosen. Addition of 0.01 mM steviol
      to the bathing medium significantly depressed J(PAH) by about 50 to 60%. Steviol
      at the same concentration (0.01 mM), when present in the tubule lumen, had no
      significant effect on J(PAH). Addition of 0.01 mM steviol to lumen and bath
      simultaneously, produced a slightly greater inhibitory effect compared with
      addition to bath alone (60 versus 70%). A higher concentration of steviol, 0.05
      mM (which maximally inhibited J(PAH) when on the basolateral side), was required
      on the luminal side than on the basolateral side before an inhibitory effect was
      observed. To further examine the mechanism by which steviol inhibited J(PAH), its
      effect on Na(+)-K(+) ATPase activity and ATP content was determined. Steviol at
      concentrations of 0.01 and 0.05 mM had no effect on Na(+)-K(+) ATPase activity or
      cell ATP content. Kinetic analyses indicated that steviol can competitively
      inhibit PAH transport at the basolateral membrane. The present study clearly
      showed that steviol can have a direct inhibitory effect on renal tubular
      transport by competitive binding with organic anion transporter.

PMID- 11504810
TI  - Suppression of acute experimental colitis by a highly selective inducible nitric
      oxide synthase inhibitor, N-[3-(aminomethyl)benzyl]acetamidine.
AB  - High concentrations of nitric oxide (NO) produced by the inducible nitric-oxide
      synthase (iNOS) are associated with ulcerative inflammation and disease activity
      in colitis. Therefore, inhibition of iNOS serves as a novel experimental approach
      to treat gut inflammation. The aim of the present study was to investigate the
      effects of a novel highly selective iNOS inhibitor, N-[3
      (aminomethyl)benzyl]acetamidine (1400W), as compared with a nonselective NOS
      inhibitor, N(G)-nitro-L-arginine-methyl-ester (L-NAME), in 2,4,6
      trinitrobenzenesulfonic acid (TNBS)-induced acute colitis in the rat. Increased
      expression of iNOS protein and mRNA was found in acute TNBS-induced colitis along
      with neutrophil infiltration, inflammatory edema, and tissue damage. In a 24-h
      model of acute colitis, subcutaneous injections of 1400W (5 or 10 mg/kg t.i.d.)
      produced a 56 and 95% reduction in inflammatory edema formation, a 68 and 63%
      reduction in neutrophil infiltration (measured as myeloperoxidase activity), and
      a 19 and 26% decrease in the size of mucosal lesions as compared with vehicle
      treatment. Administration of L-NAME (35 mg/kg) failed to produce any significant
      beneficial effects as compared with vehicle treatment in this experimental model
      of acute colitis. Treatment with 1400W, a highly selective inhibitor of iNOS,
      reduced formation of edema, neutrophil infiltration, and macroscopic inflammatory
      damage in experimentally induced acute colitis in the rat. In contrast,
      nonselective nitric-oxide synthase inhibition with L-NAME provided no benefit.
      These results support the idea that selective iNOS inhibitors have a promise in
      the treatment of colitis.

PMID- 11504811
TI  - Femtomolar concentrations of dynorphins protect rat mesencephalic dopaminergic
      neurons against inflammatory damage.
AB  - The hallmark of Parkinson's disease is the death of nigral dopaminergic neurons,
      and inflammation in the brain has been increasingly associated with the
      pathogenesis of this neurological disorder. Dynorphins are among the major opioid
      peptides in the striato-nigral pathway and are important in regulating
      dopaminergic neuronal activities. However, it is not clear whether dynorphins
      play a role in the survival of nigral dopaminergic neurons. We have recently
      demonstrated that lipopolysaccharide (LPS) activates the brain immune cells
      microglia, in vitro and in vivo, to release neurotoxic factors to degenerate
      dopaminergic neurons. The purpose of this study was to explore the
      neuroprotective effect of dynorphins in the inflammation-mediated degeneration of
      dopaminergic neurons in rat midbrain neuron-glia cultures. LPS-induced
      neurotoxicity was significantly reduced by treatment with ultra low
      concentrations (10(-13)--10(-15) M) of the kappa-opioid receptor agonist
      dynorphin A (1--17) or the receptor binding ineffective [des-Tyr(1)]dynorphin A
      (2--17), but not by U50488, a synthetic kappa-receptor agonist. The glia-mediated
      neuroprotective effect of dynorphins was further supported by the finding that
      femtomolar concentrations of dynorphins did not prevent the killing of
      dopaminergic neurons by 6-hydroxydopamine. However, ultra low concentrations of
      dynorphins inhibited LPS-induced production of superoxide. These results suggest
      a glia-mediated and conventional opioid receptor-unrelated mechanism of action
      for the neuroprotective effect of ultra low concentrations of dynorphins.
      Understanding the underlying mechanisms of action should further define the roles
      of dynorphins in the regulation of dopaminergic neurons and help devise novel
      strategies to combat neurodegenerative diseases.

PMID- 11504812
TI  - Studies on mechanisms of low emetogenicity of YM976, a novel phosphodiesterase
      type 4 inhibitor.
AB  - YM976 is a novel and selective inhibitor of phosphodiesterase type 4 (PDE4) with
      a different chemical structure from rolipram. Orally administered YM976 showed
      anti-inflammatory activity (ED(50) = 2.8 mg/kg) similar to rolipram (3.5 mg/kg).
      On the other hand, the emetogenicity of YM976, one of the main adverse effects of
      PDE4 inhibitors, was lower (maximal non-emetic dose = 10 mg/kg) than that of
      rolipram (1 mg/kg). The reasons for this low emetogenicity of YM976 remain
      unclear, and the present study endeavored to elucidate the mechanisms. Candidates
      for the possible mechanisms included 1) PDE4 subtype selectivity, 2) binding
      affinity for HAR-conformation, and 3) brain penetration. YM976 exhibited affinity
      for high affinity for rolipram-conformation (HAR-conformation) (IC(50) = 2.6 nM)
      identical to that of rolipram (1.2 nM), and failed to show significant
      selectivity for the individual PDE4 subtype. These results suggested that neither
      subtype selectivity nor the affinity for HAR-conformation may be related to the
      low emetogenicity of YM976. YM976 showed a minor effect on reserpine-induced
      hypothermia, in contrast to rolipram. To estimate brain penetration, we then
      measured cAMP contents in peripheral tissues (peritoneal macrophages) and in the
      brain. YM976 increased the cAMP content of peritoneal macrophages, but caused no
      significant increase in brain cAMP levels, while rolipram elevated the cAMP
      content of both tissues at the same dose. In conclusion, YM976 shows an apparent
      dissociation between its anti-inflammatory effects and emetogenicity, perhaps
      because of the poor brain penetration.

PMID- 11504813
TI  - Cocaine-induced increases in vesicular dopamine uptake: role of dopamine
      receptors.
AB  - The vesicular monoamine transporter-2 is the sole transporter responsible for
      sequestration of monoamines, including dopamine (DA), into synaptic vesicles.
      Previous studies demonstrate that agents that inhibit DA transporter function,
      such as cocaine, increase vesicular [(3)H]DA uptake and binding of the ligand
      [(3)H]dihydrotetrabenazine ([(3)H]DHTBZ), as assessed in vesicles prepared from
      treated rats. The present studies examine the role of DA receptors in these
      cocaine-induced effects. Results demonstrate that administration of the D(2) DA
      receptor antagonist, eticlopride, but not the D(1) DA receptor antagonist,
      SCH23390, inhibited these cocaine-induced increases. Similar to the effects of
      cocaine, treatment with the D(2) agonist, quinpirole, increased both vesicular
      [(3)H]DA uptake and [(3)H]DHTBZ binding. In contrast, administration of the D(1)
      agonist, SKF81297, was without effect on vesicular [(3)H]DA uptake or [(3)H]DHTBZ
      binding. Finally, coadministration of quinpirole and cocaine did not further
      increase vesicular [(3)H]DA uptake or [(3)H]DHTBZ binding when compared with
      treatment with either agent alone. These data suggest that cocaine-induced
      increases in vesicular DA uptake and DHTBZ binding are mediated by a D(2)
      receptor-mediated pathway. Furthermore, results indicate that D(2) receptor
      activation, per se, is sufficient to increase vesicular DA uptake.

PMID- 11504814
TI  - Selective renal vasodilation and active renal artery perfusion improve renal
      function in dogs with acute heart failure.
AB  - Renal failure is common in heart failure due to renovascular constriction and
      hypotension. We tested whether selective pharmacological renal artery
      vasodilation and active renal artery perfusion (ARP) could improve renal function
      without adverse effects on systemic blood pressure in a canine model of acute
      heart failure (AHF). AHF was induced by coronary microembolization in 16 adult
      mongrel dogs. In five dogs, selective intrarenal (IR) papaverine (1, 2, and 4
      mg/min) was administered into the left renal artery. In six dogs, ARP was
      performed in the left renal artery to normalize mean renal arterial pressure
      followed by administration of IR papaverine (2 mg/min). In five dogs, ARP plus
      intravenous furosemide was tested. Urine output (UO) and cortical renal blood
      flow decreased during AHF and were restored by 2 mg/min IR papaverine (UO:
      baseline 4.2 +/- 0.6, AHF 1.6 +/- 1.3, IR papaverine 5.8 +/- 1.1 ml/15 min;
      cortical blood flow: baseline 4.3 +/- 0.2, AHF 2.4 +/- 0.6, IR papaverine 4.2 +/-
      1.2 ml/min/g) with no significant change in aortic pressure. ARP also increased
      urine output and cortical renal blood flow (UO: baseline 5.0 +/- 1.1, AHF 0.5 +/-
      0.4, ARP 3.8 +/- 3.1 ml/15 min; cortical blood flow: baseline 4.0 +/- 0.5, AHF
      2.0 +/- 0.8, ARP 3.52 +/- 1.1 ml/min/g). A combination of these methods in AHF
      further increased urine output to twice the normal baseline (10.5 +/- 7.5 ml/15
      min). Addition of furosemide synergistically increased UO above that achieved
      with ARP alone (5.5 +/- 2.6 versus 40.3 +/- 24.7 ml/15 min, p = 0.03). In
      conclusion, ARP and selective renal vasodilation may effectively promote salt and
      water excretion in the setting of heart failure, particularly when systemic blood
      pressure is low.

PMID- 11504815
TI  - Lusitropic effect of MCC-135 is associated with improvement of sarcoplasmic
      reticulum function in ventricular muscles of rats with diabetic cardiomyopathy.
AB  - Effects of MCC-135 on contraction and relaxation properties and sarcoplasmic
      reticulum (SR) function were investigated in the failing ventricular muscle due
      to diabetic cardiomyopathy. Wistar rats were made diabetic by a single injection
      of streptozotocin (40 mg/kg i.v.). Seven months later, the left ventricular
      papillary muscle was isolated and isometric tension was measured. The skinned
      fiber with functional SR preserved was prepared by treatment of the papillary
      muscle with saponin and used to study SR Ca(2+) uptake, Ca(2+) release, and
      Ca(2+) leakage. In diabetic rats, developed tension (DT) was decreased, and 80%
      relaxation time (TR80) and time to peak tension (TTP) were increased compared
      with normal rats. MCC-135 decreased TR80 and TTP without significant effect on DT
      in diabetic rats, but not in normal rats. Isoproterenol increased DT, and
      decreased TTP and TR80 only in normal rats. In diabetic rats, SR Ca(2+) uptake
      and SR Ca(2+) release were decreased, and SR Ca(2+) leakage was increased
      compared with normal rats. MCC-135 increased SR Ca(2+) uptake and decreased SR
      Ca(2+) leakage in diabetic rats, but not in normal rats. SR Ca(2+) release was
      not affected by MCC-135 both in normal and diabetic rats. The combination of
      protein kinase A and cAMP increased SR Ca(2+) uptake only in normal rats. These
      results suggest that MCC-135 has a positive lusitropic effect that might be
      associated with enhanced Ca(2+) uptake into the SR and reduced Ca(2+) leakage
      from the SR. MCC-135 appears to be more beneficial in treating the failing
      myocardium with lusitropic abnormality than cAMP-increasing drugs.

PMID- 11504816
TI  - Voltage-dependent antagonist/agonist actions of taurine on Ca(2+)-activated
      potassium channels of rat skeletal muscle fibers.
AB  - Emerging evidence supports the idea that taurine exerts some of its actions
      through inhibition of inward rectifier K(+) channels, ATP-sensitive K(+)
      channels, and voltage-dependent K(+) channels. However, to date not much is known
      about the effects of this sulfonic amino acid on Ca(2+)-activated K(+)
      (K(Ca(2+))) channels, which are widely expressed in various tissues, including
      skeletal muscle. In the present work, the effects of taurine on K(Ca(2+))
      channels of rat skeletal muscle fibers were investigated using the patch-clamp
      technique. The application of the amino acid to the internal side of the excised
      macropatches induced a dose-dependent decrease in the outward K(Ca(2+)) currents
      recorded at positive membrane potentials in the presence of 8 to 16 microM
      concentrations of free Ca(2+) ions in the bath with an IC(50) of 31.9. 10(-3) +/-
      1 M (slope factor = 1.2) (n = 11 patches). In contrast, at negative membrane
      potentials taurine caused an enhancement of the muscular inward K(Ca(2+))
      currents with a DE(50) (drug concentration needed to enhance the current by 50%)
      of 46.7. 10(-3) +/- 2 M (slope factor = 1.3) (n = 9 patches). Single channel
      analysis revealed that this effect was mediated by changes in the reversal
      potential of the K(Ca(2+)) channel for K(+) ions with no changes in the gating
      properties or in the sensitivity of the channel to Ca(2+) ions. Taurine also did
      not affect the single channel conductance. In conclusion, taurine shows a voltage
      dependent dualistic action on K(Ca(2+)) channels, being an inhibitor of the
      channel at positive membrane potentials and an activator at negative membrane
      potentials.

PMID- 11504818
TI  - Functional characterization of rat organic anion transporter 2 in LLC-PK1 cells.
AB  - Rat organic anion transporter 2 (rOat2) is abundantly expressed in the liver and
      localized to the basolateral membrane. A previous study using the Xenopus laevis
      oocyte expression system has shown that rOat2 transports organic anions such as
      salicylate () and, in the present study, rOat2 was characterized using a
      mammalian expression system. In addition to the substrates previously shown to be
      transported by rOat2, three substrates, indomethacin [IDM, Michaelis-Menten
      constant (K(m)) of 0.37 microM] and nucleoside derivatives such as 3'-azido-3'
      deoxythymidine (AZT, K(m) of 26 microM) and 2',3'-dideoxycytidine (ddC, K(m) of
      3.08 mM), were also identified for the first time The rank order of rOat2
      mediated transport of these substrates was IDM > salicylate > prostaglandin E(2)
      > AZT > ddC > p-aminohippurate (PAH). Ketoprofen, indocyanine green and
      glibenclamide are potent inhibitors of the uptake of [(14)C]salicylate via rOat2
      (K(i) of approximately 12 microM), while diclofenac, benzoate, verapamil,
      ibuprofen, and tolbutamide are moderate inhibitors (K(i) of approximately 150
      microM). The affinity of PAH, a common substrate for the OAT family, for rOat2 is
      low (K(i) > 1 mM) compared with the other members of the OAT family (rOat1 and
      rOat3). Salicylate and IDM are also substrates for rOat1, but their affinity for
      rOat2 was higher than that for rOat1. The present study shows that rOat2 is a
      multispecific transporter and suggests that it may be involved at least partly,
      in the hepatic uptake of IDM, salicylate and nucleoside derivatives.

PMID- 11504817
TI  - Efficacy of the novel selective platelet-derived growth factor receptor
      antagonist CT52923 on cellular proliferation, migration, and suppression of
      neointima following vascular injury.
AB  - Exaggerated or inappropriate signaling by the platelet-derived growth factor
      receptor (PDGFR) tyrosine kinase has been implicated in a wide variety of
      diseases. Thus, a series of piperazinyl quinazoline compounds were identified as
      potent antagonists of the PDGFR by screening chemical libraries. An optimized
      analog, CT52923, was shown to be an ATP-competitive inhibitor that exhibited
      remarkable specificity when tested against other kinases, including all members
      of the closely related PDGFR family. The PDGFRs and stem cell factor receptor
      were inhibited with an IC(50) of 100 to 200 nM, while 45- to >200-fold higher
      concentrations of CT52923 were required to inhibit fms-like tyrosine kinase-3 and
      colony-stimulating factor-1 receptor, respectively. Other receptor tyrosine
      kinases, cytoplasmic tyrosine kinases, serine/threonine kinases, or members of
      the mitogen-activated protein kinase pathway were not significantly inhibited at
      100- to 1000-fold higher concentrations. In addition, this compound also
      demonstrated specificity for inhibition of cellular responses. Platelet-derived
      growth factor-induced smooth muscle cell migration or fibroblast proliferation
      was found to be blocked by CT52923 with an IC(50) of 64 and 280 nM, respectively,
      whereas 50- to 100-fold higher concentrations were required to inhibit these
      responses when induced with fibroblast growth factor. To investigate the effect
      of CT52923 on PDGFR signaling, in vivo studies demonstrated that CT52923 could
      significantly inhibit neointima formation following carotid artery injury by oral
      administration in the rat. Therefore, PDGFR antagonism by CT52923 could be a
      viable strategy for the prevention of clinical restenosis or the treatment of
      other human diseases involving PDGFR signaling.

PMID- 11504819
TI  - Immune stimulation by a CpG-containing oligodeoxynucleotide is enhanced when
      encapsulated and delivered in lipid particles.
AB  - The therapeutic benefit from phosphorothioate oligodeoxynucleotides (PS ODN)
      containing immune stimulatory sequences (ISS) has been demonstrated in animal
      models of cancer and infection. In particular, when CpG-containing PS ODN are
      administered to mice, activation of macrophages and dendritic, NK, T, and B cells
      occurs, resulting in the release of an array of cytokines, including interleukin
      12 (IL-12), interferon-gamma (IFN-gamma), and tumor necrosis factor-alpha (TNF
      alpha). We have previously described stabilized antisense-lipid particles (SALP)
      for the i.v. administration of antisense ODN [Biochim Biophys Acta (2001)
      1510:152--166]. Given the propensity for SALP to target macrophages in vivo it
      was of interest to determine whether they could enhance the potency of CpG ODN to
      induce an immune response. In this report we show that when CpG-containing SALP
      are administered intravenously to ICR mice the plasma concentrations of IL-12,
      IFN-gamma, IL-6, monocyte chemoattractant protein-1, and TNF-alpha are greatly
      increased compared with the same dose of free ODN. The pattern of cytokine
      induction indicates that the immune response is T helper cell type 1-biased,
      similar to that observed for PS CpG ODN ISS in general. Furthermore, when
      phosphodiester (PO) ODN is substituted for PS ODN in the SALP formulation
      cytokine induction is even greater at the early time points, in marked contrast
      to free PO ODN, which is inactive. These results demonstrate that the
      immunogenicity of ISS is not only enhanced by encapsulation in lipid particles,
      which more closely mimic the way ISS DNA would normally be presented to antigen
      presenting cells by pathogens in vivo, but also SALP enable unmodified PO CpG ODN
      to be used as immune stimulants.

PMID- 11504820
TI  - Immunosuppression by delta-opioid antagonist naltrindole: delta- and triple
      mu/delta/kappa-opioid receptor knockout mice reveal a nonopioid activity.
AB  - The delta-opioid antagonist naltrindole has been shown to inhibit graft rejection
      in vivo and suppress allogeneic mixed lymphocyte reaction (MLR) in vitro,
      similarly to cyclosporin A. We investigated whether this action is mediated by
      delta-opioid receptors using both genetic and pharmacological tools. Naltrindole
      and two related compounds, 7-benzylidene-7-dehydronaltrexone and naltriben,
      inhibited MLR performed with lymphocytes from wild-type and delta-opioid receptor
      knockout mice, with comparable potency. Furthermore, these compounds suppressed
      the proliferation of spleen cells from triple delta/mu/kappa-opioid receptor
      deficient animals as well. Finally, the highly delta-selective, but structurally
      distinct, antagonist N,N-dimethyl-Dmt-Tic-OH and the general opioid antagonist
      naltrexone were inactive in the MLR assay. In conclusion, we demonstrate for the
      first time that the immunosuppressive activity of naltrindole and close
      derivatives is not mediated by any of the three cloned opioid receptors.
      Therefore, the postulated inhibitory activity of naltrindole in the graft
      rejection process is mediated by a target, which remains to be discovered.

PMID- 11504821
TI  - Multidrug resistance-associated protein-1 functional activity in Calu-3 cells.
AB  - The purpose of this work was to determine whether the in vitro bronchiolar
      epithelial cell model, Calu-3, possesses efflux pump activity by the multidrug
      resistance-associated protein-1 (MRP1). Reverse transcription-polymerase chain
      reaction demonstrated MRP1 gene expression in Calu-3 cells. Indirect fluorescence
      studies showed a basolateral membrane localization of MRP1 compared with P
      glycoprotein (Pgp) that was found on the apical side of these cells. An increase
      in the rate of accumulation of the MRP1 substrate calcein was observed following
      treatment with the organic anion/MRP1 inhibitor indomethacin, the Pgp inhibitors
      cyclosporin A (CsA) and vinblastine, as well as conditions of energy depletion.
      Total calcein efflux was significantly decreased with the MRP1 inhibitors
      probenecid and indomethacin, while total efflux was unchanged following treatment
      with CsA. In the latter case, however, intracellular calcein levels postefflux
      were significantly greater. Probenecid and indomethacin increased calcein net
      secretion 2.4- and 3.5-fold, respectively. The efflux of etoposide, a known
      substrate for both Pgp and MRP1, was shown to be mainly Pgp-mediated by using the
      multidrug-resistant inhibitors quinidine (mixed Pgp/MRP1), CsA (Pgp), and MK571
      (MRP1). Together, these data suggest that Calu-3 cells possess MRP1 functional
      activity that is subordinate to Pgp efflux. We present here kinetic analysis of
      calcein efflux from Calu-3 cells to support our findings.

PMID- 11504822
TI  - Liposomal and nonliposomal drug pharmacokinetics after administration of liposome
      encapsulated vincristine and their contribution to drug tissue distribution
      properties.
AB  - We have determined the pharmacokinetics of liposomal vincristine, in a Lewis lung
      carcinoma solid tumor model in mice, with the aim of differentiating the
      contribution of liposomal and nonliposomal (released from liposomes) drug pools
      to the overall pharmacokinetic profile. Two types of liposomal formulations were
      used: one composed of 1,2 distearoyl-sn-glycero-3-phosphocholine/cholesterol
      (Chol) (55/45; mol/mol) and the other composed of sphingomyelin/cholesterol
      (SM/Chol; 55/45; mol/mol). Vincristine elimination from the circulation after
      injection of conventional, aqueous formulated vincristine (C-VINC) was
      characterized by a short half-life (1.36 h), low plasma area under the plasma
      concentration-time curve (AUC) (0.59 microg x h/ml), and large volume of
      distribution (145 ml). Total drug elimination from the circulation after
      liposomal vincristine injection using SM/Chol liposomes was characterized by a
      prolonged half-life (6.6 h), increased plasma AUC (213 microg x h/ml) and small
      volume of distribution (2.0 ml). Our results indicate that > or =98% of the total
      vincristine measured in the plasma of mice administered with liposomal
      vincristine was encapsulated within the liposomes. The systemic exposure to free
      drug after administration of liposomal formulations was significantly lower than
      that observed after the injection of C-VINC. Plasma concentrations of free drug
      remained between 0.025 and 0.05 microg/ml over 4 h of postinjection for both
      liposomal formulations. In contrast, concentrations between 0.1 and 0.35
      microg/ml were observed following C-VINC administration. Free plasma drug
      concentrations did not correlate with vincristine tissue distribution properties
      following administration of liposomal vincristine formulations. Rather,
      accumulation of vincristine in tissues appeared to be influenced primarily by the
      drug retention properties of the liposome. While the reduced systemic exposure to
      free vincristine correlates with reduced toxicity, additional information (such
      as liposome drug release properties) may be necessary to correlate
      pharmacokinetic behavior with antitumor activity.

PMID- 11504823
TI  - Ovarian sex steroid-dependent plasticity of nociceptin/orphanin FQ and opioid
      modulation of spinal dynorphin release.
AB  - Pregnancy and its hormonal simulation via 17beta-estradiol (E(2)) and
      progesterone (P) are associated with spinal opioid antinociception, primarily
      driven by augmented dynorphin/kappa-opioid activity. This study addresses the
      ovarian sex steroid-activated mechanism(s) that underlie this activation using an
      ex vivo spinal cord preparation. In lumbar spinal cord obtained from control
      animals, exogenous kappa- or delta-opioid agonists (but not mu), as well as
      nociceptin (orphanin FQ; N/OFQ), dose dependently inhibit the stimulated release
      of dynorphin. Consistent with these observations, stimulated dynorphin release is
      enhanced following selective blockade of opioid or N/OFQ receptors, indicating
      that their endogenous ligands are negative modulators of dynorphin release. In
      lumbar spinal cord obtained from ovariectomized animals exposed to pregnancy
      blood levels of E(2)/P, basal and stimulated rates of dynorphin release increase
      approximately 2-fold. Moreover, evoked dynorphin release is no longer negatively
      modulated by kappa- or delta-opioid agonists or N/OFQ. Interestingly, in these
      preparations, release can be facilitated by delta-opioid receptor activation, and
      neither spinal opioid nor N/OFQ receptor blockade enhances evoked dynorphin
      release. Consistent with these observations, guanosine-5'-O-3-[(35)S]-thio
      triphosphate binding analyses indicate a reduction in functional N/OFQ receptors.
      These data indicate that at least part of the E(2)/P-induced augmented activity
      of lumbar dynorphin neurons results from their disinhibition via the removal of
      negative opioid and N/OFQ modulation. These results underscore the plasticity of
      spinal opioid and N/OFQ systems and their dependence on the ovarian sex steroid
      milieu. Ovarian sex steroid-activated antinociception reveals mechanisms that
      enable sustained opioid activation without concomitant tolerance formation.

PMID- 11504824
TI  - Limited efficacy of thalidomide in the treatment of febrile attacks of the hyper
      IgD and periodic fever syndrome: a randomized, double-blind, placebo-controlled
      trial.
AB  - Hyper-IgD and periodic fever syndrome (HIDS) is an autosomal recessive disorder
      featured by recurrent febrile attacks. Previous unpublished experience (J. van
      der Meer and R. Powell) suggested that thalidomide may prevent febrile attacks.
      Six HIDS patients (5 male and 1 female) who had at least one febrile attack every
      6 weeks, entered a randomized, double-blind, placebo-controlled crossover trial
      to explore the efficacy of a daily 200-mg thalidomide dose in the treatment of
      recurrent febrile attacks of HIDS. The patients received either thalidomide, 200
      mg daily, or placebo for 16 weeks, followed by a 4-week washout period and
      another 16-week treatment (crossover) with either thalidomide or placebo.
      Patients completed a weekly diary card noting attacks and side effects. During
      the study, C-reactive protein (CRP), serum amyloid A (SAA), interleukin (IL)-6,
      tumor necrosis factor (TNF)-alpha, IL-1 receptor antagonist, soluble TNF receptor
      p55 and p75, and lipopolysaccharide-stimulated IL-1 beta and TNF-alpha production
      were measured at six different points, whereas urine neopterin levels were
      measured weekly. During the active treatment with thalidomide, there were 10
      attacks compared with 13 attacks with placebo. Thalidomide resulted in a
      nonsignificant decrease of CRP and SAA, but the concentrations of other
      inflammatory mediators, including urine neopterin, remained unchanged. One
      patient developed sensory polyneuropathy, but this resolved when thalidomide
      administration was stopped. The effect of thalidomide in HIDS is limited to a
      decrease in acute phase protein synthesis without an effect on the attack rate.

PMID- 11504825
TI  - Potency of positive gamma-aminobutyric acid(A) modulators to substitute for a
      midazolam discriminative stimulus in untreated monkeys does not predict potency
      to attenuate a flumazenil discriminative stimulus in diazepam-treated monkeys.
AB  - In monkeys discriminating midazolam (0.56 mg/kg s.c.) from saline, substitution
      for midazolam was elicited by various positive gamma-aminobutyric acid(A)
      (GABA(A)) modulators, including the benzodiazepines (BZs) triazolam, midazolam,
      and diazepam; the BZ(1)-selective ligands zaleplon and zolpidem; the barbiturates
      amobarbital and pentobarbital; and the neuroactive steroid pregnanolone. In
      another group of diazepam (5.6 mg/kg/day p.o.)-treated monkeys discriminating
      flumazenil (0.32 mg/kg s.c.) from vehicle, these positive GABA(A) modulators
      shifted the flumazenil dose-effect function to the right, i.e., attenuated
      diazepam withdrawal. The potency of positive GABA(A) modulators to substitute for
      midazolam in untreated monkeys did not predict their potency to attenuate the
      flumazenil stimulus in diazepam-treated monkeys. For instance, larger doses of
      BZs and BZ(1)-selective ligands were required to attenuate the flumazenil
      stimulus than to substitute for midazolam. The opposite relationship was revealed
      for non-BZ ligands, i.e., smaller doses of barbiturates and a neuroactive steroid
      were required to attenuate the flumazenil stimulus than to substitute for
      midazolam. The greater potency of non-BZ site ligands to attenuate diazepam
      withdrawal might be due to actions at a subtype of GABA(A) receptor not modulated
      by BZ site ligands, to the development of BZ tolerance without cross-tolerance to
      non-BZ site ligands, or to noncompetitive interactions at the GABA(A) receptor
      complex. Thus, interactions among GABA(A) modulators in BZ-dependent subjects are
      not predicted by their acute actions in nondependent subjects. It is not clear
      whether attenuation of BZ withdrawal is determined by subunit specificity or site
      of action on the GABA(A) receptor complex.

PMID- 11504826
TI  - Kinetics of P-glycoprotein-mediated efflux of paclitaxel.
AB  - Paclitaxel is a substrate of the mdr1 P-glycoprotein (Pgp). The objective of the
      present study was to determine the kinetics of the Pgp-mediated efflux and its
      contribution to the overall efflux of paclitaxel at the clinically achievable
      concentration range of 1 to 1500 nM. Human breast carcinoma BC19 cells that were
      derived from MCF7 cells by mdr1 transfection and show a >10-fold higher level of
      the Pgp protein were used to measure the uptake and efflux of [(3)H]paclitaxel. A
      computational model of intracellular paclitaxel pharmacokinetics was developed to
      analyze for the Pgp efflux parameters. The results show a saturable Pgp-mediated
      efflux in BC19 cells; the dissociation constant was 14 nM, and the maximal efflux
      rate was 2.8 x 10(-4) pmol/h/cell. The contribution of Pgp-mediated efflux to the
      total efflux decreased with increasing extracellular drug concentrations; the Pgp
      efflux accounted for 86 and 34% of total efflux at 1 and 1500 nM, respectively.
      The validity of the model was confirmed by the close agreement between the model
      predicted data and the experimentally obtained data (approximately 6% deviation)
      describing the effect of cell density and intracellular-to-extracellular
      concentration gradient on the kinetics of drug accumulation and efflux. In
      conclusion, our results indicate that the Pgp-mediated efflux represents a major
      efflux mechanism of paclitaxel at the low end of the clinically observed drug
      concentration range, but accounts for only a minor part of the efflux at higher
      concentrations in BC19 cells.

PMID- 11504827
TI  - Phosphorylation and desensitization of the human thromboxane receptor-alpha by G
      protein-coupled receptor kinases.
AB  - The thromboxane A(2) receptor (TP), which mediates vasoconstriction, mitogenesis,
      and platelet aggregation, has been shown to undergo rapid agonist-induced
      desensitization. Two isoforms (alpha and beta) of TP have been recognized. The
      potential role of the G protein-coupled receptor kinases (GRKs) in the
      phosphorylation and desensitization of TP alpha was investigated. Human embryonic
      kidney (HEK) 293 cells stably transfected with the His-tagged TP alpha was used
      to study the phosphorylation and desensitization of the receptor. Rapid isolation
      of the (32)P-labeled receptor was achieved by Ni(2+)-nitrilotriacetic acid
      agarose after agonist stimulation of HEK293 cells prelabeled with (32)P(i). [1S
      [1 alpha,2 alpha(Z),3 beta(1E,3S*),4 alpha]]-7-[3-[3-Hydroxy-4-(4-iodophenoxy)-1
      butenyl]-7-oxabicyclo[2,2,1]hept-2-yl]-5-heptenoic acid (I-BOP) induced receptor
      phosphorylation and Ca(2+) release in a time- and dose-dependent manner.
      Pretreatment of cells with I-BOP abolished subsequent induction of Ca(2+) release
      through a second dose of I-BOP. Transfection with expression plasmids encoding
      the cDNA of GRK5 or GRK6 augmented I-BOP-induced phosphorylation and inhibited I
      BOP-stimulated Ca(2+) release. Both I-BOP-induced and GRK-mediated
      phosphorylation and phorbol ester-induced phosphorylation were blocked by the
      addition of 2-[1-(3-dimethylaminopropyl)-1H-indol-3-yl]-3-(1H-indol-3-yl)
      maleimide) (GF 109203X). This indicates that GF 109203X, a known protein kinase C
      (PKC) inhibitor, also inhibits GRKs. This finding was further supported by in
      vitro studies in which preparations of GRK5 and GRK6 were found to be inhibited
      by GF 109203X. These results suggest that GRK5 and GRK6 may phosphorylate the TP
      alpha in an agonist-dependent manner. Furthermore, the results obtained with PKC
      inhibitors in assessing the role of PKC in agonist-induced receptor
      phosphorylation should be interpreted with caution.

PMID- 11504828
TI  - P-glycoprotein efflux at the blood-brain barrier mediates differences in brain
      disposition and pharmacodynamics between two structurally related neurokinin-1
      receptor antagonists.
AB  - CP-122721 and CP-141938 are potent and selective neurokinin-1 (NK(1)) receptor
      antagonists with very different brain disposition and potency in models of
      centrally mediated activity. These investigations sought to determine whether
      differences in potency were related to differences in P-glycoprotein (P-gp)
      transport at the blood-brain barrier. Both compounds stimulated ATPase activity
      of human recombinant MDR1 with similar kinetic parameters. Cell-associated drug
      concentrations of CP-141938 were 9.4-fold lower in KBV1 cells expressing P-gp
      compared with KB3.1 control cells. In Madin-Darby canine kidney (MDCK) cells
      expressing human MDR1, asymmetric transport of CP-141938 was 5-fold higher than
      in wild-type MDCK cells, whereas no asymmetry was observed with CP-122721. In
      agreement with these differences in cellular transport, the differences in
      brain/plasma ratio between mdr1a/b(-/-) and FVB mice 1 h following a 3 mg/kg s.c.
      dose were 3- and 50-fold for CP-122721 and CP-141938, respectively. The effect of
      inhibiting P-gp efflux on the effects of these agents was evaluated using GR73632
      induced foot tapping in gerbils as a model to measure centrally mediated NK(1)
      antagonism. When gerbils were pretreated with the P-gp inhibitor MS-073 (50 mg/kg
      s.c.), there was no effect on the activity of CP-122721 (0.05 mg/kg), whereas the
      percent reversal for CP-141938 (10 mg/kg) increased from 60 to 100%. In gerbils,
      the brain/plasma ratio for CP-122721 was unaffected by MS-073 pretreatment,
      whereas the brain/plasma ratio for CP-141938 brain concentrations increased 13
      fold. This suggested that P-gp efflux influences the brain disposition and
      pharmacologic activity of CP-141938, but not CP-122721. Complete response curves
      for CP-141938 were then determined with respect to dose, and drug concentration
      in the plasma and brain in the presence and absence of MS-073 pretreatment. The
      dose and plasma concentration-response curves of CP-141938 were shifted to the
      left in the presence of MS-073, yet brain concentrations associated with the
      response were unchanged. This suggested that once in the brain the interaction of
      CP-141938 with the NK(1) receptor was not affected by P-gp transport. In
      conclusion, these studies show that brain disposition and centrally mediated in
      vivo activity of NK(1) antagonists can be profoundly affected by P-gp transport
      and that such transport should be considered during the design of new agents.

PMID- 11504829
TI  - Synthesis and pharmacological evaluation of dimeric muscarinic acetylcholine
      receptor agonists.
AB  - Two dimeric analogs of the muscarinic acetylcholine receptor (mAChR) agonist
      phenylpropargyloxy-1,2,5-thiadiazole-quinuclidine (NNC 11-1314) were synthesized
      and pharmacologically evaluated. In radioligand binding assays on Chinese hamster
      ovary (CHO) cell membranes expressing the individual human M(1) to M(5) mAChR
      subtypes, both dimers [(3S)-1,4-bis-(3-[(3-azabicyclo[2.2.2]octanyl)-1,2,5
      thiadiazol-4-yloxy]-1-propyn-1-yl)benzene,2-L-(+)-tartrate (NNC 11-1607) and (3S)
      1,3-bis-(3-[(3-azabicyclo[2.2.2]octanyl)-1,2,5-thiadiazol-4-yloxy]-1-propyn-1
      yl)benzene,2-L-(+)-tartrate (NNC 11-1585)] exhibited higher binding affinities
      than the monomeric NNC 11-1314. Only NNC 11-1585, however, displayed significant
      selectivity for the M(1) and M(2) mAChRs relative to the other subtypes. Although
      binding studies in rat brain homogenates supported the selectivity profile of NNC
      11-1585 observed in the CHO membranes, rat heart membrane experiments revealed
      complex binding behavior for all three agonists that most likely reflected
      differences in species and host cell environment between the heart and CHO cells.
      Subsequent functional assays with phosphatidylinositol hydrolysis revealed that
      all three novel ligands were partial agonists relative to the full agonist
      oxotremorine-M at the CHO M(1), M(3), and M(5) mAChRs, with NNC 11-1607
      displaying the highest functional selectivity. In the CHO M(2) and M(4) mAChR
      cells, agonist-mediated effects on forskolin-stimulated cAMP accumulation were
      characterized by bell-shaped concentration-response curves, with the exceptions
      of NNC 11-1607, which had no discernible effects at the M(2) mAChR, and NNC 11
      1585, which could only inhibit cAMP accumulation at the M(4) mAChR. Thus, we
      identified NNC 11-1607 as a novel functionally selective M(1)/M(4) mAChR agonist.
      Our data suggest that dimerization of mAChR agonists is a viable approach in
      designing more potent and functionally selective agonists, as well as in
      providing novel tools with which to probe the nature of agonism at these
      receptors.

PMID- 11504830
TI  - The antidepressant-like effect induced by sigma(1)-receptor agonists and
      neuroactive steroids in mice submitted to the forced swimming test.
AB  - The interaction of neuroactive steroids with the sigma(1)-receptor was
      investigated in Swiss mice submitted to the forced swimming test. The sigma(1)
      agonists igmesine and (+)-SKF-10,047 and the steroid dehydroepiandrosterone
      sulfate (DHEAS) showed some antidepressant-like activity by shortening the
      immobility time, these effects being blocked by the sigma(1)-antagonist BD1047 or
      progesterone. The sigma(1)-agonist PRE-084 or pregnenolone sulfate failed to
      affect the immobility time. In adrenalectomized/castrated (AdX/CX) mice, the
      effects of igmesine and DHEAS were significantly potentiated, and PRE-084 or
      pregnenolone sulfate induced significant decreases of immobility time. The
      augmented effects in AdX/CX were fully blocked by BD1047. The effects of the
      classical antidepressants, desipramine or fluoxetine, were unchanged in AdX/CX
      mice. The effect of stress on the sigma(1)-receptor binding and neurosteroid
      levels was then examined in different brain structures, in terms of in vivo (+)
      [(3)H]SKF-10,047 binding to sigma(1)-sites and neurosteroids levels. In the
      hippocampus, but not in the cortex or cerebellum, inhibition of in vivo (+)
      [(3)H]SKF-10,047 binding was measured in parallel to the extent of progesterone
      levels according to the endocrine conditions. These data confirmed the
      antidepressant ability of sigma(1)-receptor agonists and revealed that the
      endogenous steroidal levels tonically interfere with the efficacy of the sigma(1)
      system. It was observed that local modifications in progesterone levels are
      directly related to the changes of in vivo sigma(1)-binding. Such observations
      may be of major importance in view of the therapeutic use of selective sigma(1)
      agonists in depression.

PMID- 11504831
TI  - Disruption of mitochondrial function and cellular ATP levels by amiodarone and N
      desethylamiodarone in initiation of amiodarone-induced pulmonary cytotoxicity.
AB  - Amiodarone (AM), a potent antidysrhythmic agent, can cause potentially life
      threatening pulmonary fibrosis. In the present investigation of mechanisms of
      initiation of AM lung toxicity, we found that 100 microM AM decreased
      mitochondrial membrane potential in intact hamster lung alveolar macrophages and
      preparations enriched in isolated alveolar type II cells and nonciliated
      bronchiolar epithelial (Clara) cells, following 2 h of incubation. This was
      followed by a drop in cellular ATP content (by 32--77%) at 4 to 6 h, and 30 to
      55% loss of viability at 24 h. Supplementation of incubation media with 5.0 mM
      glucose or 2.0 mM niacin did not reduce AM-induced ATP depletion or cell death in
      macrophages, and the mitochondrial permeability transition inhibitor cyclosporin
      A (1.0 microM) did not affect AM cytotoxicity. At 50 microM, the AM metabolite N
      desethylamiodarone (DEA) produced effects similar to those of AM, but more
      rapidly and extensively, with the Clara cell-enriched preparation being
      particularly susceptible. In isolated whole lung mitochondria, DEA was
      accumulated to a greater extent than AM. Both AM and DEA inhibited complex I- and
      complex II-supported respiration, but DEA inhibited complex II to a greater
      degree than AM. These results demonstrate that AM and DEA disrupt mitochondrial
      membrane potential prior to ATP depletion and subsequent lung cell death, that
      DEA is more potent than AM, and that the mitochondrial permeability transition is
      not involved in mitochondrial perturbation by AM. This suggests that AM- and DEA
      induced perturbations of mitochondrial function may initiate AM-induced pulmonary
      toxicity.

PMID- 11504832
TI  - Expression of Bax and apoptosis-related proteins in human esophageal squamous
      cell carcinoma including dysplasia.
AB  - The rate of tumor growth depends on the balance between proliferation and death
      of tumor cells. It is known that Bax, caspase-3, and p53 proteins are death
      promoting factors, whereas Bcl-2 protein is a death antagonist. We
      immunohistochemically examined the expression of Bax and apoptosis-related
      proteins such as caspase-3, p53, and Bcl-2 in 76 patients with human esophageal
      squamous cell carcinoma (SCC) including dysplasia to determine the relationship
      of expression of each protein to tumor behavior and patients' prognosis. No
      significant relationships in immunopositivity were found among these proteins in
      SCCs. Cytoplasmic Bax expression was exhibited in 63 cases of SCCs (82.9%). The
      apoptotic index of caspase-3-positive lesions was significantly higher than that
      of caspase-3-negative lesions in both dysplasia and SCC (P =.016, P =.012). On
      the other hand, the apoptotic index (1.18%) was significantly correlated with Bax
      overexpression in dysplasia (P =.006), but not in SCC lesions (P =.129). The
      patients with Bax-positive SCCs were found to have a poor prognosis by the Kaplan
      Meier method (P =.043). These findings suggested that Bax expressed in dysplasia
      may play a role as an apoptotic factor, but that it may be functionally inactive
      in some cancerous lesions and thus not contribute to suppression of the tumor
      progression in some cases of human esophageal SCCs.

PMID- 11504833
TI  - Glucose transporter Glut-1 is of limited value for detecting breast carcinoma in
      serous effusions.
AB  - Diagnosing breast carcinoma that has metastasized to body cavity fluids can be
      difficult. Recently, immunostaining for the facultative glucose transporter Glut
      1 has been described as a sensitive and specific means of detecting carcinomas in
      effusions. However, only five cases of breast carcinoma were studied. We examined
      Glut-1 specifically as a means of detecting breast carcinoma in effusion
      cytology. Using avidin-biotin immunocytochemistry, cell block material from 31
      cases of breast carcinoma metastatic to body cavity effusions and 33 cases of
      benign effusions were studied. All cases were immunostained with the Glut-1
      antibody. An additional set of slides from these same cases was stained for mucin
      using the Mayer's mucicarmine technique. Slides were graded for percentage of
      cells exhibiting immunoreactivity for Glut-1 or for the presence of mucin.
      Results of staining for both Glut-1 alone and in combination with mucicarmine
      were compared between the benign and malignant groups. Of the breast cancer
      cases, 19 of 31 (61%) were immunoreactive for Glut-1, and 25 of 31 (81%) were
      positive for either Glut-1 or mucicarmine. One of the 33 (3%) benign cases was
      immunoreactive for Glut-1, and none were positive for mucin. These data suggest
      that using Glut-1 as a single immunostain or in conjunction with mucicarmine is a
      specific but modestly sensitive means of detecting breast carcinoma in this
      cytologic setting.

PMID- 11504834
TI  - Identification of the target cells of Orientia tsutsugamushi in human cases of
      scrub typhus.
AB  - Orientia tsutsugamushi is the etiologic agent of scrub typhus, a chigger-borne
      zoonosis that is a highly prevalent, life-threatening illness of greatest public
      health importance in tropical Asia and the islands of the western Pacific Ocean.
      The target cell of this bacterium is poorly defined in humans. In this study, O.
      tsutsugamushi were identified by immunohistochemistry using a rabbit polyclonal
      antibody raised against O. tsutsugamushi Karp strain in paraffin-embedded
      archived autopsy tissues of three patients with clinical suspicion of scrub
      typhus who died during World War II and the Vietnam War. Rickettsiae were located
      in endothelial cells in all of the organs evaluated, namely heart, lung, brain,
      kidney, pancreas, and skin, and within cardiac muscle cells and in macrophages
      located in liver and spleen. Electron microscopy confirmed the location of
      rickettsiae in endothelium and cardiac myocytes.

PMID- 11504835
TI  - Parvalbumin is constantly expressed in chromophobe renal carcinoma.
AB  - Chromophobe renal carcinoma is composed of neoplastic cell showing several
      features similar to those found in the intercalated cells of the collecting
      ducts. Because the distal nephron expresses calcium-binding proteins playing a
      role in calcium homeostasis, we reasoned that these proteins could be expressed
      by chromophobe carcinoma and therefore represent a diagnostic marker. We studied
      the immunohistochemical expression of different calcium-binding proteins
      (parvalbumin, calbindin-D28K, and calretinin) in 140 renal tumors, including 75
      conventional (clear cell) carcinomas, 32 chromophobe carcinomas, 17 papillary
      renal cell carcinomas, and 16 oncocytomas. Parvalbumin was strongly positive in
      all primary chromophobe carcinomas and in one pancreatic metastasis; it was
      positive in 11 of 16 oncocytomas and absent in conventional (clear cell) and
      papillary renal cell carcinomas, either primary or metastatic. Calbindin-D28K and
      calretinin were negative in all tumors, with the exception of two chromophobe
      carcinomas, four oncocytomas, and two papillary renal cell carcinomas showing
      inconspicuous calretinin expression. Our data demonstrate that parvalbumin may be
      a suitable marker for distinguishing primary and metastatic chromophobe carcinoma
      from conventional (clear cell) and papillary renal cell carcinoma. Moreover, they
      suggest a relationship between chromophobe renal carcinoma and renal oncocytoma
      and indicate that chromophobe carcinoma exhibits differentiation toward the
      collecting-duct phenotype.

PMID- 11504837
TI  - Prognostic relevance of hMLH1, hMSH2, and BAX protein expression in endometrial
      carcinoma.
AB  - Endometrial carcinoma is the most common gynecologic malignancy in perimenopausal
      and postmenopausal women. A role of mismatch repair genes, like hMLH1 and hMSH2
      in their pathogenesis, has been suggested. Loss of their function leads to the
      accumulation of replication errors (mutator phenotype), which are responsible for
      further mutations in genes with microsatellite sequences in their coding region,
      such as Bax. We analyzed the expression of hMLH1, hMSH2, and Bax genes in 89
      formalin-fixed paraffin-embedded endometrial carcinomas. The immunostains were
      scored with regard to percentage of positive tumor cells (0%, <10%, 10 to 50%,
      >50%), and relative staining intensity (1+, 2+, 3+). The staining results were
      correlated with clinicopathologic features and survival. Loss of hMSH2 expression
      (0% positive cells) was observed in 1.1% (1/89) of the tumors; loss of hMLH1 was
      seen in 12.4% (11/89) of the cases, particularly in endometrioid tumors with
      mucinous differentation (5/11; 45%; P =.03). No significant association was found
      between the immunoscores and grade, stage criteria of the International
      Federation of Obstetrics and Gynecology (FIGO), or age of the patients. Among 11
      tumors with loss of Bax expression (12.4%), 4 had also loss of hMLH1 (4/11;
      36.4%; P =.017). In multivariate analysis (Cox model), significantly longer
      survival was found for patients with tumors in FIGO Stage I-II (P <.0001),
      endometrioid type (P =.001), low grade (P =.001), and absence of hMLH1 expression
      (P =.027). Our results suggest that loss of function of hMLH1 and Bax occur in a
      subgroup of endometrial carcinoma. In addition to the classical prognostic
      factors, absence of hMLH1 expression is associated with better outcome of
      patients.

PMID- 11504836
TI  - Expression of apocrine differentiation markers in neuroendocrine breast
      carcinomas of aged women.
AB  - Neuroendocrine (NE) breast carcinomas are a rare entity in young women; however,
      their frequency increases in aged patients. The present work demonstrates that NE
      breast carcinomas in elderly women can also express an apocrine immunophenotype
      and analyzes the histological and clinical aspects of such differentiation. A
      selected series of 50 NE tumors (positive for NE markers in >/=50% of the cells)
      was tested for the immunocytochemical expression of gross cystic disease fluid
      protein-15 (GCDFP-15). The results demonstrated that about 50% of moderately (G2)
      and well-differentiated (G1) NE breast carcinomas (mucinous, solid papillary, and
      solid cohesive histotypes) coexpressed the apocrine marker. In these cases,
      specific mRNA for GCDFP-15 (PIP) and for chromogranin A (ChA) was demonstrated
      using in situ hybridization (ISH). Carcinomas of the alveolar subtype (G2) and
      poorly differentiated carcinomas (G3), including one case of atypical carcinoid,
      were pure NE carcinomas, devoid of apocrine differentiation. The steroid receptor
      status of these lesions was evaluated to test a possible involvement of androgen
      receptors in apocrine differentiation. We demonstrated that the level of AR and
      the mean age of patients at diagnosis were significantly higher in apocrine than
      in nonapocrine differentiated tumors. The histological grade and the expression
      of estrogen receptor (ER) significantly influenced the prognosis of these NE
      carcinomas, either pure or NE-apocrine differentiated. The most original result
      of our study is therefore the demonstration of a possible divergent apocrine
      differentiation of NE breast carcinomas that might be regulated by the activation
      of androgen receptors in elder patients. In addition, the possibility for using
      Chs or GCDFP-15 serum values in the follow-up of these patients, as demonstrated
      in two cases of the present series, can justify the immunophenotyping of the
      tumors.

PMID- 11504838
TI  - Calcifying fibrous pseudotumor versus inflammatory myofibroblastic tumor: a
      histological and immunohistochemical comparison.
AB  - Calcifying fibrous pseudotumor (CFP), a recently described lesion, is
      characterized by a predominantly lymphoplasmacytic infiltrate with abundant
      hyalinized collagen and psammomatous or dystrophic calcifications. The cause and
      pathogenesis are unclear, but it has been postulated that CFP may represent a
      sclerosing end stage of inflammatory myofibroblastic tumor (IMT). We compared the
      histological and immunohistochemical profiles of seven cases diagnosed as CFP and
      seven as IMT. Histologically, the CFP demonstrated varying degrees of
      calcifications in addition to fibroblastic proliferation admixed with
      inflammatory cells composed of lymphocytes, eosinophils, and mast cells. The IMTs
      rarely contain calcifications and had a myofibroblastic proliferation varying
      from hyalinized acellular collagen to florid fibroblastic proliferations
      simulating sarcoma. The inflammatory component was composed primarily of plasma
      cells and lymphocytes, sometimes arranged as lymphoid aggregates with germinal
      centers. All CFP cases were diffusely positive for factor XIIIa and negative for
      smooth muscle actin, muscle-specific actin, and CD34. All IMTs demonstrated
      diffuse positivity for actin, variable positivity for CD34, and focal positivity
      for Factor XIIIa. This study demonstrates certain distinct histologic,
      immunohistochemical, and electron microscopic features between IMTs and CFPs.

PMID- 11504839
TI  - Expression of interleukin-6, interleukin-6 receptor (gp80), and the receptor's
      signal-transducing subunit (gp130) in human normal pituitary glands and pituitary
      adenomas.
AB  - Interleukin-6 (IL-6) is an important cytokine in cell proliferation and
      differentiation in several organs. It has also been reported that IL-6 plays a
      role in secretion or release of pituitary hormones in pituitary hormone-secreting
      cells and pituitary adenomas, but convincing data in situ have not yet been
      reported. In this study, we examined the participation of IL-6 in the production
      of pituitary hormones and the differences between human normal pituitary glands
      and pituitary adenomas by determination of the localization or expression of IL
      6, IL-6 receptor (IL-6R, gp80), and the signal-transducing subunit (gp130) of the
      receptor using immunohistochemical staining and RT-PCR. IL-6 was mainly expressed
      in ACTH- and FSH/LH-secreting cells in normal pituitary glands, as shown by
      double staining. gp 80 and gp130 were coexpressed in almost all GH- and PRL
      secreting cells and in approximately 30% of FSH/LH-secreting cells. RT-PCR showed
      that IL-6 mRNA was expressed in only one of all the pituitary adenomas examined,
      whereas gp 80 and gp 130 mRNAs were detected in all these pituitary adenomas. In
      conclusion, IL-6 was mainly expressed in ACTH- and FSH/LH-secreting cells, and
      the receptors were expressed in GH-, PRL- and FSH/LH-secreting cells in human
      normal pituitary glands. Furthermore, our data emphasized that the mechanism of
      IL-6 function in human pituitary adenoma cells is distinct from that in normal
      pituitary cells.

PMID- 11504840
TI  - Loss of expression of alpha4beta7 integrin and L-selectin is associated with high
      grade progression of low-grade MALT lymphoma.
AB  - Expression of adhesion molecule in low-grade B-cell mucosa-associated lymphoid
      tissue (MALT) lymphoma of the gastrointestinal tract has been reported in recent
      years, but these reports have primarily focused on low-grade gastrointestinal
      MALT lymphoma. In this study, we examined the lymphocytic homing receptor
      alpha4beta7 integrin, L-selectin, and VLA-4 and mucosal addressin cell adhesion
      molecule-1 (MAdCAM-1) in low-grade lymphoma of the gastrointestinal tract and
      other organs such as the ocular adnexa and thyroid. We also observed changes in
      the expression pattern associated with high-grade transformation. Neoplastic
      cells in the gastrointestinal low-grade lymphoma and the low-grade component of
      high-grade MALT lymphoma were found to be alpha4beta7 integrin(+), L-selectin(+),
      whereas the gastrointestinal high-grade component and diffuse large B-cell
      lymphoma were found to be alpha4beta7 integrin(-), L-selectin(-). High
      endothelial venules in the gastric MALT lymphomas expressed MAdCAM-1. In the
      ocular adnexa low-grade MALT lymphoma, most cases were alpha4beta7 integrin(-), L
      selectin(+); and in the thyroid, most cases of both low- and high-grade MALT
      lymphoma were alpha4beta7 integrin(-), L-selectin(-). These findings show that
      alpha4beta7 integrin and L-selectin may play an important role in the lymphocyte
      homing of gastrointestinal low-grade MALT lymphoma and in the loss of alpha4beta7
      integrin expression throughout the course of high-grade progression.

PMID- 11504841
TI  - Evaluation of crystals in formalin-fixed, paraffin-embedded tissue sections for
      the differential diagnosis of pseudogout, gout, and tumoral calcinosis.
AB  - Hematoxylin-eosin (H&E)-stained sections may not allow proper evaluation of
      birefringence properties of the crystals in the lesions of pseudogout, gout, and
      tumoral calcinosis. This study was undertaken to verify the application of a
      special stain that could facilitate the evaluation of the birefringence
      properties of these crystals for definitive diagnosis. We evaluated previously
      described nonaqueous alcoholic eosin staining (NAES) method based on the
      principle of using alcoholic eosin without hematoxylin and any other aqueous
      reagents for staining of formalin-fixed, paraffin-embedded tissue sections. Two
      observers, in a blinded fashion, evaluated the sections stained with routine H&E
      and NEAS method without the knowledge about clinical diagnosis. All pseudogout
      (nine sections from seven cases) and gout (eight sections from five cases)
      lesions demonstrated birefringence in the sections stained with NAES method. H&E
      stained sections showing the respective diagnostic histomorphology failed to
      demonstrate the birefringent crystals by polarizing microscopy in all the eight
      sections from gout and in seven of nine sections from pseudogout. Only two H&E
      stained sections showed scant calcium pyrophosphate dihydrate (CPPD) crystals in
      pseudogout. None of the three sections from two cases of tumoral calcinosis
      showed birefringence with either stain. We conclude that CPPD in pseudogout and
      monosodium urate in gout may not polarize in the routine H&E-stained sections.
      However, polarizing microscopy of sections stained with NAES method allowed
      demonstration of CPPD crystals with positive birefringence in pseudogout, MSU
      crystals with negative birefringence in gout, and calcium hydroxyapatite crystals
      without birefringence in tumoral calcinosis. Section stained with NAES method is
      a significantly useful adjunct to the routine H&E stain for proper evaluation of
      the crystals under polarizing microscope in these lesions.

PMID- 11504842
TI  - Early phase of intestinal mantle cell lymphoma: a report of two cases associated
      with advanced colonic adenocarcinoma.
AB  - Intestinal mantle cell lymphoma characteristically produces multiple polyps, a
      finding reported as multiple lymphomatous polyposis. The early stages of
      intestinal mantle cell lymphoma before polyp formation and the pattern of initial
      lymph node invasion, however, have not been described. We recently encountered
      two cases of intestinal mantle cell lymphoma in their early development found
      incidentally associated with advanced colonic adenocarcinoma. We present herein
      the clinical, histopathological, immunohistochemical, and molecular genetic
      features of these two cases. In one case, a single polypoid mass was found with
      invasion limited to mucosa and submucosa of the terminal ileum and without lymph
      node compromise. In the second case, there were multiple mucosal aggregates of
      neoplastic cells without formation of polyps. Regional lymph nodes in the latter
      case showed either partial or complete involvement by lymphoma. In both cases,
      immunohistochemistry (CD20+, CD5+, cyclin D1+, CD10-, and CD23-), and
      demonstration of clonal immunoglobulin heavy chain and bcl-1 gene rearrangements
      by PCR analysis confirmed the diagnosis of mantle cell lymphoma.

PMID- 11504843
TI  - The evolution of controlled multitasked gene networks: the role of introns and
      other noncoding RNAs in the development of complex organisms.
AB  - Eukaryotic phenotypic diversity arises from multitasking of a core proteome of
      limited size. Multitasking is routine in computers, as well as in other
      sophisticated information systems, and requires multiple inputs and outputs to
      control and integrate network activity. Higher eukaryotes have a mosaic gene
      structure with a dual output, mRNA (protein-coding) sequences and introns, which
      are released from the pre-mRNA by posttranscriptional processing. Introns have
      been enormously successful as a class of sequences and comprise up to 95% of the
      primary transcripts of protein-coding genes in mammals. In addition, many other
      transcripts (perhaps more than half) do not encode proteins at all, but appear
      both to be developmentally regulated and to have genetic function. We suggest
      that these RNAs (eRNAs) have evolved to function as endogenous network control
      molecules which enable direct gene-gene communication and multitasking of
      eukaryotic genomes. Analysis of a range of complex genetic phenomena in which RNA
      is involved or implicated, including co-suppression, transgene silencing, RNA
      interference, imprinting, methylation, and transvection, suggests that a higher
      order regulatory system based on RNA signals operates in the higher eukaryotes
      and involves chromatin remodeling as well as other RNA-DNA, RNA-RNA, and RNA
      protein interactions. The evolution of densely connected gene networks would be
      expected to result in a relatively stable core proteome due to the multiple reuse
      of components, implying that cellular differentiation and phenotypic variation in
      the higher eukaryotes results primarily from variation in the control
      architecture. Thus, network integration and multitasking using trans-acting RNA
      molecules produced in parallel with protein-coding sequences may underpin both
      the evolution of developmentally sophisticated multicellular organisms and the
      rapid expansion of phenotypic complexity into uncontested environments such as
      those initiated in the Cambrian radiation and those seen after major extinction
      events.

PMID- 11504844
TI  - Evolutionary dynamics of multiple group I introns in nuclear ribosomal RNA genes
      of endoparasitic fungi of the genus Cordyceps.
AB  - A large number of group I introns were discovered in coding regions of small and
      large subunits of nuclear ribosomal RNA genes (SSU rDNA and LSU rDNA) in
      ascomycetous fungi of the genus CORDYCEPS: From 28 representatives of the genus,
      we identified in total 69 group I introns which were inserted at any of four
      specific sites in SSU rDNA and four specific sites in LSU rDNA. These group I
      introns reached sizes of up to 510 bp, occurred in up to eight sites in the same
      organism, and belonged to either subgroup IB3 or subgroup IC1 based on their
      sequence and structure. Introns inserted at the same site were closely related to
      each other among Cordyceps fungi, whereas introns inserted at different sites
      were phylogenetically distinct even in the same species. Mapped on the host
      phylogeny, the group I introns were generally not restricted to a particular
      lineage, but, rather, widely and sporadically distributed among distinct
      lineages. When the phylogenetic relationships of introns inserted at the same
      site were compared with the phylogeny of their hosts, the topologies were
      generally significantly congruent to each other. From these results, the
      evolutionary dynamics of multiple group I introns in Cordyceps fungi was inferred
      as follows: (1) most of the group I introns were already present at the eight
      sites in SSU and LSU rDNAs of the ancestor of the genus Cordyceps; (2) the
      introns have principally been immobile and vertically transmitted throughout
      speciation and diversification of Cordyceps fungi, which resulted in the
      phylogenetic congruence between the introns at the same site and their hosts; (3)
      in the course of vertical transmission, the introns have repeatedly been lost in
      a number of lineages independently, which has led to the present sporadic
      phylogenetic distribution of the introns; and (4) a few acquisitions of new
      introns, presumably through horizontal transmission, were identified in the
      evolutionary history of the genus Cordyceps, while no transpositions were
      detected. Losses of group I introns in SSU rDNA have occurred at least 27 times
      in the evolutionary course of the 28 Cordyceps members.

PMID- 11504845
TI  - Molecular evolution of Aldolase A pseudogenes in mice: multiple origins,
      subsequent duplications, and heterogeneity of evolutionary rates.
AB  - The Aldolase multigene family comprises three functional genes (A, B, and C) with
      tissue-specific expression regulated during ontogeny. DGGE analysis and
      nucleotide sequencing reveal a family of retropseudogenes of type A in species of
      MUS: Significant variation in rates of evolution of Aldolase A retropseudogenes
      is apparent. Our analyses demonstrate that (1) multiple events of
      retrotransposition are needed to account for the diversity of Aldolase A
      processed pseudogenes found in mice; (2) some of these sequences have undergone
      further duplication subsequent to the original retrotransposition event; (3) the
      patterns of nucleotide substitution are broadly comparable with previous
      estimates; and (4) estimates of rates of divergence for this array of sequences
      are up to four times higher than those reported in the literature.

PMID- 11504846
TI  - A structural and phylogenetic analysis of the group IC1 introns in the order
      Bangiales (Rhodophyta).
AB  - Our previous study of the North American biogeography of Bangia revealed the
      presence of two introns inserted at positions 516 and 1506 in the nuclear-encoded
      SSU rRNA gene. We subsequently sequenced nuclear SSU rRNA in additional
      representatives of this genus and the sister genus Porphyra in order to examine
      the distribution, phylogeny, and structural characteristics of these group I
      introns. The lengths of these introns varied considerably, ranging from 467 to
      997 nt for intron 516 and from 509 to 1,082 nt for intron 1506. The larger
      introns contained large insertions in the P2 domain of intron 516 and the P1
      domain of intron 1506 that correspond to open reading frames (ORFs) with His-Cys
      box homing endonuclease motifs. These ORFs were found on the complementary strand
      of the 1506 intron in Porphyra fucicola and P. umbilicalis (HG), unlike the 516
      intron in P. abbottae, P. kanakaensis, P. tenera (SK), Bangia fuscopurpurea
      (Helgoland), and B. fuscopurpurea (MA). Frameshifts were noted in the ORFs of the
      516 introns in P. kanakaensis and B. fuscopurpurea (HL), and all ORFs terminated
      prematurely relative to the amino acid sequence for the homing endonuclease I-Ppo
      I. This raises the possibility that these sequences are pseudogenes. Phylogenies
      generated using sequences of both introns and the 18S rRNA gene were congruent,
      which indicated long-term immobility and vertical inheritance of the introns
      followed by subsequent loss in more derived lineages. The introns within the
      florideophyte species Hildenbrandia rubra (position 1506) were included to
      determine relationships with those in the Bangiales. The two sequences of intron
      1506 analyzed in Hildenbrandia were positioned on a well-supported branch
      associated with members of the Bangiales, indicating possible common ancestry.
      Structural analysis of the intron sequences revealed a signature structural
      feature in the P5b domain of intron 516 that is unique to all Bangialean introns
      in this position and not seen in intron 1506 or other group IC1 introns.

PMID- 11504847
TI  - Structural evolution of Otx genes in craniates.
AB  - Using a degenerate PCR approach, we performed an exhaustive search of Otx genes
      in the reedfish Erpetoichthys calabaricus, the dogfish Scyliorhinus canicula, and
      the hagfish Myxine glutinosa. Three novel Otx genes were identified in each of
      these species, and their deduced protein sequences were determined over a large C
      terminal fragment located immediately downstream of the homeodomain. Like their
      lamprey and osteichthyan counterparts, these nine genes display a tandem
      duplication of a 20--25-residue C-terminal domain, which appears to be a hallmark
      of all craniate Otx genes identified thus far, including the highly divergent Crx
      gene. Phylogenetic analyses show that, together with their osteichthyan
      counterparts, the dogfish and reedfish genes can be classified into three
      gnathostome orthology classes. Two of the three genes identified in each of these
      species belong to the Otx1 and Otx2 orthology classes previously characterized in
      osteichthyans. The third one unambiguously clusters with the Otx5/Otx5b genes
      recently characterized in Xenopus laevis, thus defining a novel orthology class.
      Our results also strongly suggest that the highly divergent Crx genes identified
      in humans, rodents, and oxen are the mammalian representatives of this third
      class. The hagfish genes display no clear relationships to the three gnathostome
      orthology classes, but one of them appears to be closely related to the LjOtxA
      gene, previously identified in Lampetra japonica. Taken together, these data
      support the hypothesis that the Otx multigene families characterized in craniates
      all derive from duplications of a single ancestral gene which occurred after the
      splitting of cephalochordates but prior to the gnathostome radiation. Using site
      by-site sequence comparisons of the gnathostome Otx proteins, we also identified
      structural constraints selectively acting on each of the three gnathostome
      orthology classes. This suggests that specialized functions for each of these
      orthology classes were fixed in the gnathostome lineage prior to the splitting
      between osteichthyans and chondrichthyans.

PMID- 11504849
TI  - Scale-free behavior in protein domain networks.
AB  - Several technical, social, and biological networks were recently found to
      demonstrate scale-free and small-world behavior instead of random graph
      characteristics. In this work, the topology of protein domain networks generated
      with data from the ProDom, Pfam, and Prosite domain databases was studied. It was
      found that these networks exhibited small-world and scale-free topologies with a
      high degree of local clustering accompanied by a few long-distance connections.
      Moreover, these observations apply not only to the complete databases, but also
      to the domain distributions in proteomes of different organisms. The extent of
      connectivity among domains reflects the evolutionary complexity of the organisms
      considered.

PMID- 11504848
TI  - Genetic identification of wild and domestic cats (Felis silvestris) and their
      hybrids using Bayesian clustering methods.
AB  - Crossbreeding with free-ranging domestic cats is supposed to threaten the genetic
      integrity of wildcat populations in Europe, although the diagnostic markers to
      identify "pure" or "admixed" wildcats have never been clearly defined. Here we
      use mitochondrial (mt) DNA sequences and allelic variation at 12 microsatellite
      loci to genotype 128 wild and domestic cats sampled in Italy which were
      preclassified into three separate groups: European wildcats (Felis silvestris
      silvestris), Sardinian wildcats (Felis silvestris libyca), and domestic cats
      (Felis silvestris catus), according to their coat color patterns, collection
      localities, and other phenotypical traits, independently of any genetic
      information. For comparison, we included some captive-reared hybrids of European
      wild and domestic cats. Genetic variability was significantly partitioned among
      the three groups (mtDNA estimate of F(ST) = 0.36; microsatellite estimate of
      R(ST) = 0.30; P < 0.001), suggesting that morphological diversity reflects the
      existence of distinct gene pools. Multivariate ordination of individual genotypes
      and clustering of interindividual genetic distances also showed evidence of
      distinct cat groups, partially congruent with the morphological classification.
      Cluster analysis, however, did not enable hybrid cats to be identified from
      genetic information alone, nor were all individuals assigned to their
      populations. In contrast, a Bayesian admixture analysis simultaneously assigned
      the European wildcats, the Sardinian wildcats, and the domestic cats to different
      clusters, independent of any prior information, and pointed out the admixed gene
      composition of the hybrids, which were assigned to more than one cluster. Only
      one putative Sardinian wildcat was assigned to the domestic cat cluster, and one
      presumed European wildcat showed mixed (hybrid) ancestry in the domestic cat gene
      pool. Mitochondrial DNA sequences indicated that three additional presumed
      European wildcats might have hybrid ancestry. These four cats were sampled from
      the same area in the northernmost edge of the European wildcat distribution in
      the Italian Apennines. Admixture analyses suggest that wild and domestic cats in
      Italy are distinct, reproductively isolated gene pools and that introgression of
      domestic alleles into the wild-living population is very limited and
      geographically localized.

PMID- 11504850
TI  - Translational selection on codon usage in Xenopus laevis.
AB  - A correspondence analysis of codon usage in Xenopus laevis revealed that the
      first axis is strongly correlated with the base composition at third codon
      positions. The second axis discriminates between putatively highly expressed
      genes and the other coding sequences, with expression levels being confirmed by
      the analysis of Expressed sequence tag frequencies. The comparison of codon usage
      of the sequences displaying the extreme values on the second axis indicates that
      several codons are statistically more frequent among the highly expressed (mainly
      housekeeping) genes. Translational selection appears, therefore, to influence
      synonymous codon usage in Xenopus.

PMID- 11504851
TI  - Recurrent amplifications and deletions of satellite DNA accompanied chromosomal
      diversification in South American tuco-tucos (genus Ctenomys, Rodentia:
      Octodontidae): a phylogenetic approach.
AB  - We investigated the relationship between satellite copy number and chromosomal
      evolution in tuco-tucos (genus Ctenomys), a karyotypically diverse clade of
      rodents. To explore phylogenetic relationships among 23 species and 5 undescribed
      forms, we sequenced the complete mitochondrial cytochrome b genes of 27 specimens
      and incorporated 27 previously published sequences. We then used quantitative dot
      blot techniques to assess changes in the copy number of the major Ctenomys
      satellite DNA (satDNA), named RPCS. Our analysis of the relationship between
      variation in copy number of RPCS and chromosomal changes employed a maximum
      likelihood approach to infer the copy number of the satellite RPCS in the
      ancestors of each clade. We found that amplifications and deletions of RPCS were
      associated with extensive chromosomal rearrangements even among closely related
      species. In contrast, RPCS copy number stability was observed within clades
      characterized by chromosomal stability. This example reinforces the suspected
      role of amplification, deletion, and intragenomic movement of satDNA in promoting
      extensive chromosomal evolution.

PMID- 11504852
TI  - Chromosome mapping and phylogenetic analysis of the cytosolic acetyl-CoA
      carboxylase loci in wheat.
AB  - The cytosolic isoform of plant acetyl-CoA carboxylase is a multidomain enzyme
      involved in the synthesis of very-long-chain fatty acids and in secondary
      metabolism. Chromosome mapping of wheat identified one locus containing cytosolic
      acetyl-CoA carboxylase genes (Acc-2) and a related partially processed pseudogene
      (Psi-Acc-2) in the distal region of the long arm of wheat homoeologous group 3
      chromosomes. Multiple copies of the Acc-2 genes, whose presence was suggested by
      sequence analysis, are likely to be arranged in tandem repeats. At least three
      out of five genes cloned from hexaploid wheat map to this locus. Another locus
      containing Acc-2--related sequences is present in the distal region of the long
      arm of chromosome 5D. The identity of the hybridizing DNA present at this locus
      remains unknown. A system based on PCR-cloning and DNA sequence analysis of
      acetyl-CoA carboxylase genes was developed to address various phylogenetic and
      systematics questions in grasses. It was applied to reconstruct the phylogeny of
      the Acc-2 genes from D- and S-genome Aegilops and A-genome Triticum diploid
      species, AABB- and AAGG-genome tetraploid wheat, and AABBDD-genome hexaploid
      wheat, as well as from rye and barley. The combined cytogenetic and molecular
      evolution approach allowed assignment of gene sequences included in phylogenetic
      analysis to specific loci on homoeologous chromosomes. Recurring gene duplication
      followed by chromosome translocation and/or possible loss of some gene copies, as
      well as loss of introns, occurred in the gene family in different plant lineages.
      Two major Acc-2 clades appeared before the divergence of barley and rye.
      Nucleotide substitution rates in different parts of the Acc-2 gene were assessed.
      This analysis of the Acc-2 loci provides detailed information regarding
      evolutionary events at a low--copy-number locus containing important functional
      genes. These events are likely to be common and to play a significant role in
      shaping grass genomes.

PMID- 11504853
TI  - The complete mitochondrial genome of the articulate brachiopod Terebratalia
      transversa.
AB  - We sequenced the complete mitochondrial DNA (mtDNA) of the articulate brachiopod
      Terebratalia transversa. The circular genome is 14,291 bp in size, relatively
      small compared with other published metazoan mtDNAs. The 37 genes commonly found
      in animal mtDNA are present; the size decrease is due to the truncation of
      several tRNA, rRNA, and protein genes, to some nucleotide overlaps, and to a
      paucity of noncoding nucleotides. Although the gene arrangement differs radically
      from those reported for other metazoans, some gene junctions are shared with two
      other articulate brachiopods, Laqueus rubellus and Terebratulina retusa. All
      genes in the T. transversa mtDNA, unlike those in most metazoan mtDNAs reported,
      are encoded by the same strand. The A+T content (59.1%) is low for a metazoan
      mtDNA, and there is a high propensity for homopolymer runs and a strong base
      compositional strand bias. The coding strand is quite G+T-rich, a skew that is
      shared by the confamilial (laqueid) species L. rubellus but is the opposite of
      that found in T. retusa, a cancellothyridid. These compositional skews are
      strongly reflected in the codon usage patterns and the amino acid compositions of
      the mitochondrial proteins, with markedly different usages being observed between
      T. retusa and the two laqueids. This observation, plus the similarity of the
      laqueid noncoding regions to the reverse complement of the noncoding region of
      the cancellothyridid, suggests that an inversion that resulted in a reversal in
      the direction of first-strand replication has occurred in one of the two
      lineages. In addition to the presence of one noncoding region in T. transversa
      that is comparable with those in the other brachiopod mtDNAs, there are two
      others with the potential to form secondary structures; one or both of these may
      be involved in the process of transcript cleavage.

PMID- 11504854
TI  - Was the ANITA rooting of the angiosperm phylogeny affected by long-branch
      attraction? Amborella, Nymphaeales, Illiciales, Trimeniaceae, and Austrobaileya.
AB  - Five groups of basal angiosperms, Amborella, Nymphaeales, Illiciales,
      Trimeniaceae, and Austrobaileya (ANITA), were identified in several recent
      studies as representing a series of the earliest-diverging lineages of the
      angiosperm phylogeny. All of these studies except one employed a multigene
      analysis approach and used gymnosperms as the outgroup to determine the ingroup
      topology. The high level of divergence between gymnosperms and angiosperms,
      however, has long been implicated in the difficulty of reconstructing
      relationships at the base of angiosperm phylogeny using DNA sequences, for fear
      of long-branch attraction (LBA). In this study, we replaced the gymnosperm
      sequences from the five-gene matrix (mitochondrial atp1 and matR, plastid atpB
      and rbcL, and nuclear 18S rDNA) used in our earlier study with four categories of
      divergent sequences--random sequences with equal base frequencies or equally AT-
      and GC-rich contents, homopolymers and heteropolymers, misaligned gymnosperm
      sequences, and aligned lycopod and bryophyte sequences--to evaluate whether the
      gymnosperms were an appropriate outgroup to angiosperms in our earlier study that
      identified the ANITA rooting. All 24 analyses performed rooted the angiosperm
      phylogeny at either Acorus or Alisma (or Alisma-Triglochin-Potamogeton in one
      case due to use of a slightly different alignment) and placed the monocots as a
      basal grade, producing genuine LBA results. These analyses demonstrate that the
      identification of ANITA as the basalmost extant angiosperms was based on
      historical signals preserved in the gymnosperm sequences and that the gymnosperms
      were an appropriate outgroup with which to root the angiosperm phylogeny in the
      multigene sequence analysis. This strategy of evaluating the appropriateness of
      an outgroup using artificial sequences and a series of outgroups with increments
      of divergence levels can be applied to investigations of phylogenetic patterns at
      the bases of other major clades, such as land plants, animals, and eukaryotes.

PMID- 11504855
TI  - Trichome distribution in Arabidopsis thaliana and its close relative Arabidopsis
      lyrata: molecular analysis of the candidate gene GLABROUS1.
AB  - GLABROUS1 (GL1) belongs to the large family of MYB transcription factors and is
      known to play a central role in trichome initiation. We studied trichome
      distribution and the molecular variation of GL1 in 28 A. thaliana accessions.
      Trichome density on rosette leaves was highly variable among those accessions. On
      the molecular level, we detected substantial sequence variation in a 3-kb
      fragment which included the complete coding region of the GL1 locus (pi = 0.01).
      Phylogenetic analysis of GL1 indicates the presence of two diverged clades among
      28 accessions. Using ANOVA, we show that the phenotypic variation in trichome
      density cannot be explained by the sequence divergence between the two
      phylogenetic lineages. Sequence analysis of wild-type Arabidopsis thaliana and
      Arabidopsis lyrata accessions indicates that all amino acid substitutions are
      located outside of the conserved helix-turn-helix DNA-binding domains R2 and R3.
      Using plants of A. thaliana and A. lyrata with either naturally occurring or
      ethyl methane sulfonate--induced glabrous phenotypes, we demonstrate that the
      last 14 C-terminal amino acids of the GL1 gene have no major impact on the
      initiation of trichomes.

PMID- 11504856
TI  - Rapid evolution of cis-regulatory sequences via local point mutations.
AB  - Although the evolution of protein-coding sequences within genomes is well
      understood, the same cannot be said of the cis-regulatory regions that control
      transcription. Yet, changes in gene expression are likely to constitute an
      important component of phenotypic evolution. We simulated the evolution of new
      transcription factor binding sites via local point mutations. The results
      indicate that new binding sites appear and become fixed within populations on
      microevolutionary timescales under an assumption of neutral evolution. Even
      combinations of two new binding sites evolve very quickly. We predict that local
      point mutations continually generate considerable genetic variation that is
      capable of altering gene expression.

PMID- 11504857
TI  - A combined analysis of the cystic fibrosis transmembrane conductance regulator:
      implications for structure and disease models.
AB  - Over the past decade, nearly 1,000 variants have been identified in the cystic
      fibrosis transmembrane conductance regulator (CFTR) gene in classic and atypical
      cystic fibrosis (CF) patients worldwide, and an enormous wealth of information
      concerning the structure and function of the protein has also been accumulated.
      These data, if evaluated together in a sequence comparison of all currently
      available CFTR homologs, are likely to refine the global structure-function
      relationship of the protein, which will, in turn, facilitate interpretation of
      the identified mutations in the gene. Based on such a combined analysis, we had
      recently defined a "functional R domain" of the CFTR protein. First, presenting
      two full-length cDNA sequences (termed sCFTR-I and sCFTR-II) from the Atlantic
      salmon (Salmo salar) and an additional partial coding sequence from the eastern
      gray kangaroo (Macropus giganteus), this study went further to refine the
      boundaries of the two nucleotide-binding domains (NBDs) and the COOH-terminal
      tail (C-tail), wherein NBD1 was defined as going from P439 to G646, NBD2 as going
      from A1225 to E1417, and the C-tail as going from E1418 to L1480. This approach
      also provided further insights into the differential roles of the two halves of
      CFTR and highlighted several well-conserved motifs that may be involved in inter-
      or intramolecular interactions. Moreover, a serious concern that a certain
      fraction of missense mutations identified in the CFTR gene may not have
      functional consequences was raised. Finally, phylogenetic analysis of all the
      full-length CFTR amino acid sequences and an extended set of exon 13--coding
      nucleotide sequences reinforced the idea that the rabbit may represent a better
      CF model than the mouse and strengthened the assertion that a long-branch
      attraction artifact separates the murine rodents from the rabbit and the guinea
      pig, the other Glires.

PMID- 11504858
TI  - Ongoing evolution of strand composition in bacterial genomes.
AB  - We tried to identify the substitutions involved in the establishment of
      replication strand bias, which has been recognized as an important evolutionary
      factor in the evolution of bacterial genomes. First, we analyzed the composition
      asymmetry of 28 complete bacterial genomes and used it to test the possibility
      that asymmetric deamination of cytosine might be at the origin of the bias. The
      model showed significant correlation to the data but left unexplained a
      significant portion of the variance and indicated a systematic underestimation of
      GC skews in comparison with TA skews. Second, we analyzed the substitutions
      acting on the genes from five fully sequenced Chlamydia genomes that had not
      suffered strand switch since speciation. This analysis showed that substitutions
      were not at equilibrium in Chlamydia trachomatis or in C. muridarum and that
      strand bias is still an on-going process in these genes. Third, we identified
      substitutions involved in the adaptation of genes that had switched strands after
      speciation. These genes adapted quickly to the skewed composition of the new
      strand, mostly due to C-->T, A-->G, and C-->G asymmetric substitutions. This
      observation was reinforced by the analysis of genes that switched strands after
      divergence between Bacillus subtilis and B. halodurans. Finally, we propose a
      more extended model based on the analysis of the substitution asymmetries of
      CHLAMYDIA: This model fits well with the data provided by bacterial genomes
      presenting strong strand bias.

PMID- 11504859
TI  - Snake alpha-neurotoxin binding site on the Egyptian cobra (Naja haje) nicotinic
      acetylcholine receptor Is conserved.
AB  - Evolutionary success requires that animal venoms are targeted against
      phylogenetically conserved molecular structures of fundamental physiological
      processes. Species producing venoms must be resistant to their action. Venoms of
      Elapidae snakes (e.g., cobras, kraits) contain alpha-neurotoxins, represented by
      alpha-bungarotoxin (alpha-BTX) targeted against the nicotinic acetylcholine
      receptor (nAChR) of the neuromuscular junction. The model which presumes that
      cobras (Naja spp., Elapidae) have lost their binding site for conspecific alpha
      neurotoxins because of the unique amino acid substitutions in their nAChR
      polypeptide backbone per se is incompatible with the evolutionary theory that (1)
      the molecular motifs forming the alpha-neurotoxin target site on the nAChR are
      fundamental for receptor structure and/or function, and (2) the alpha-neurotoxin
      target site is conserved among Chordata lineages. To test the hypothesis that the
      alpha-neurotoxin binding site is conserved in Elapidae snakes and to identify the
      mechanism of resistance against conspecific alpha-neurotoxins, we cloned the
      ligand binding domain of the Egyptian cobra (Naja haje) nAChR alpha subunit. When
      expressed as part of a functional Naja/mouse chimeric nAChR in Xenopus oocytes,
      this domain confers resistance against alpha-BTX but does not alter responses
      induced by the natural ligand acetylcholine. Further mutational analysis of the
      Naja/mouse nAChR demonstrated that an N-glycosylation signal in the ligand
      binding domain that is unique to N. haje is responsible for alpha-BTX resistance.
      However, when the N-glycosylation signal is eliminated, the nAChR containing the
      N. haje sequence is inhibited by alpha-BTX with a potency that is comparable to
      that in mammals. We conclude that the binding site for conspecific alpha
      neurotoxin in Elapidae snakes is conserved in the nAChR ligand binding domain
      polypeptide backbone per se. This conclusion supports the hypothesis that animal
      toxins are targeted against evolutionarily conserved molecular motifs. Such
      conservation also calls for a revision of the present model of the alpha-BTX
      binding site. The approach described here can be used to identify the mechanism
      of resistance against conspecific venoms in other species and to characterize
      toxin-receptor coevolution.

PMID- 11504861
TI  - Traditional phylogenetic reconstruction methods reconstruct shallow and deep
      evolutionary relationships equally well.

PMID- 11504860
TI  - Accelerated evolution of functional plastid rRNA and elongation factor genes due
      to reduced protein synthetic load after the loss of photosynthesis in the
      chlorophyte alga Polytoma.
AB  - Polytoma obtusum and Polytoma uvella are members of a clade of nonphotosynthetic
      chlorophyte algae closely related to Chlamydomonas humicola and other
      photosynthetic members of the Chlamydomonadaceae. Descended from a
      nonphotosynthetic mutant, these obligate heterotrophs retain a plastid
      (leucoplast) with a functional protein synthetic system, and a plastid genome
      (lpDNA) with functional genes encoding proteins required for transcription and
      translation. Comparative studies of the evolution of genes in chloroplasts and
      leucoplasts can identify modes of selection acting on the plastid genome. Two
      plastid genes--rrn16, encoding the plastid small-subunit rRNA, and tufA, encoding
      elongation factor Tu--retain their functions in protein synthesis after the loss
      of photosynthesis in two nonphotosynthetic Polytoma clades but show a
      substantially accelerated rate of base substitution in the P. uvella clade. The
      accelerated evolution of tufA is due, at least partly, to relaxed codon bias
      favoring codons that can be read without wobble, mainly in three amino acids.
      Selection for these codons may be relaxed because leucoplasts are required to
      synthesize fewer protein molecules per unit time than are chloroplasts (reduced
      protein synthetic load) and thus require a lower rate of synthesis of elongation
      factor Tu. Relaxed selection due to a lower protein synthetic load is also a
      plausible explanation for the accelerated rate of evolution of rrn16, but the
      available data are insufficient to test the hypothesis for this gene. The tufA
      and rrn16 genes in Polytoma oviforme, the sole member of a second
      nonphotosynthetic clade, are also functional but show no sign of relaxed
      selection.

PMID- 11504862
TI  - Increased rate of gene rearrangement in the mitochondrial genomes of three orders
      of hemipteroid insects.

PMID- 11504863
TI  - The Human Genome Project reveals a continuous transfer of large mitochondrial
      fragments to the nucleus.

PMID- 11504864
TI  - Intragenomic base content variation is a potential source of biases when
      searching for horizontally transferred genes.

PMID- 11504865
TI  - Thermodynamic stability of base pairs between 2-hydroxyadenine and incoming
      nucleotides as a determinant of nucleotide incorporation specificity during
      replication.
AB  - We investigated the thermodynamic stability of double-stranded DNAs with an
      oxidative DNA lesion, 2-hydroxyadenine (2-OH-Ade), in two different sequence
      contexts (5'-GA*C-3' and 5'-TA*A-3', A* represents 2-OH-Ade). When an A*-N pair
      (N, any nucleotide base) was located in the center of a duplex, the thermodynamic
      stabilities of the duplexes were similar for all the natural bases except A (N =
      T, C and G). On the other hand, for the duplexes with the A*-N pair at the end,
      which mimic the nucleotide incorporation step, the stabilities of the duplexes
      were dependent on their sequence. The order of stability is T > G > C >> A in the
      5'-GA*C-3' sequences and T > A > C > G in the 5'-TA*A-3' sequences. Because T/G/C
      and T/A are nucleotides incorporated opposite to 2-OH-Ade in the 5'-GA*C-3' and
      5'-TA*A-3' sequences, respectively, these results agree with the tendency of
      mutagenic misincorporation of the nucleotides opposite to 2-OH-Ade in vitro.
      Thus, the thermodynamic stability of the A*-N base pair may be an important
      factor for the mutation spectra of 2-OH-Ade.

PMID- 11504866
TI  - Repression of rRNA synthesis due to a secretory defect requires the C-terminal
      silencing domain of Rap1p in Saccharomyces cerevisiae.
AB  - A secretory defect causes specific transcriptional repression of both ribosomal
      protein and ribosomal RNA genes, suggesting the coupling of plasma membrane and
      ribosome syntheses. We previously reported that the rap1-17 allele, which
      produced C-terminally truncated Rap1p, derepressed transcription of ribosomal
      protein genes when the secretory pathway was blocked. In this paper, we
      demonstrate that the rap1-17 mutation also leads to significant attenuation of
      transcriptional repression of rRNA genes due to a secretory defect. In contrast,
      the rap1-2 temperature-sensitive allele containing a unique missense mutation in
      the middle of the coding sequence has only a weak effect on repression. These
      results suggest that the C-terminal silencing domain of Rap1p is required for
      transcriptional repression of rDNA in response to a secretory defect. We also
      demonstrated that transcriptional regulation of ribosomal protein genes in
      response to nitrogen limitation was not affected by the rap1-17 allele,
      suggesting that the mechanism of nitrogen response is distinct from that of the
      secretory response.

PMID- 11504867
TI  - Suppression of gene amplification and chromosomal DNA integration by the DNA
      mismatch repair system.
AB  - Mismatch repair (MMR)-deficient cells are shown to produce >15-fold more
      methotrexate-resistant colonies than MMR normal cells. The increased resistance
      to methotrexate is primarily due to gene amplification since all the resistant
      clones contain double-minute chromosomes and increased copy numbers of the DHFR
      gene. In addition, integration of linearized or retroviral DNAs into chromosomes
      is also significantly elevated in MMR-deficient cells. These results suggest that
      in addition to microsatellite instability and homeologous recombination, MMR is
      also involved in suppression of other genome instabilities such as gene
      amplification and chromosomal DNA integration.

PMID- 11504869
TI  - Initiation of DNA replication by DNA polymerases from primers forming a triple
      helix.
AB  - Despite extensive studies on oligonucleotide-forming triple helices, which were
      discovered in 1957, their possible relevance in the initiation of DNA replication
      remains unknown. Using sequences forming triple helices, we have developed a DNA
      polymerisation assay by using hairpin DNA templates with a 3' dideoxynucleotide
      end and an unpaired 5'-end extension to be replicated. The T7 DNA polymerase
      successfully elongated nucleotides to the expected size of the template from the
      primers forming triple helices composed of 9-14 deoxyguanosine-rich residues. The
      triple helix-forming primer required for this reaction has to be oriented
      parallel to the homologous sequence of the hairpin DNA template. Substitution of
      the deoxyguanosine residues by N7 deazadeoxyguanosines in the hairpin of the
      template prevented primer elongation, suggesting that the formation of a triple
      helix is a prerequisite for primer elongation. Furthermore, DNA sequencing could
      be achieved with the hairpin template through partial elongation of the third DNA
      strand forming primer. The T4 DNA polymerase and the Klenow fragment of DNA
      polymerase I provided similar DNA elongation to the T7 polymerase-thioredoxin
      complex. On the basis of published crystallographic data, we show that the third
      DNA strand primer fits within the catalytic centre of the T7 DNA polymerase, thus
      underlying this new property of several DNA polymerases which may be relevant to
      genome rearrangements and to the evolution of the genetic apparatus, namely the
      DNA structure and replication processes.

PMID- 11504868
TI  - Electrostatic control of half-site spacing preferences by the cyclic AMP response
      element-binding protein CREB.
AB  - Basic region leucine zipper (bZIP) proteins represent a class of transcription
      factors that bind DNA using a simple, dimeric, alpha-helical recognition motif.
      The cAMP response element-binding protein (CREB) is a member of the CREB/ATF
      subfamily of bZIP proteins. CREB discriminates effectively in vivo and in vitro
      between the 10 bp cAMP response element (ATGACGTCAT, CRE) and the 9 bp activating
      protein 1 site (ATGACTCAT, AP-1). Here we describe an alanine scanning
      mutagenesis study designed to identify those residues within the CREB bZIP
      element that control CRE/AP-1 specificity. We find that the preference of CREB
      for the CRE site is controlled in a positive and negative way by acidic and basic
      residues in the basic, spacer and zipper segments. The CRE/AP-1 specificity of
      CREB is increased significantly by four glutamic acid residues located at
      positions 24, 28, 35 and 41; glutamic acid residues at positions 10 and 48
      contribute in a more modest way. Specificity is decreased significantly by two
      basic residues located at positions 21 and 23; basic residues at positions 14,
      18, 33 and 34 and V17 contribute in a more modest way. All of the residues that
      influence specificity significantly are located on the solvent-exposed face of
      the protein-DNA complex and likely participate in interactions between and among
      proteins, not between protein and DNA. The finding that the CRE/AP-1 specificity
      of CREB is dictated by the presence or absence of charged residues has
      interesting implications for how transcription factors seek and selectively bind
      sequences within genomic DNA.

PMID- 11504870
TI  - Composition and arrangement of genes define the strength of IRES-driven
      translation in bicistronic mRNAs.
AB  - In addition to the cap-dependent mechanism, eukaryotic initiation of translation
      can occur by a cap-independent mechanism which directs ribosomes to defined start
      codons enabled by internal ribosome entry site (IRES) elements. IRES elements
      from poliovirus and encephalomyocarditis virus are often used to construct bi- or
      oligocistronic expression vectors to co-express various genes from one mRNA. We
      found that while cap-dependent translation initiation from bicistronic mRNAs
      remains comparable to monocistronic expression, internal initiation mediated by
      these viral IRESs is often very inefficient. Expression of bicistronic expression
      vectors containing the hepatitis B virus core antigen (HBcAg) together with
      various cytokines in the second cistron of bicistronic mRNAs gave rise to very
      low levels of the tested cytokines. On the other hand, the HBcAg was well
      expressed when positioned in the second cistron. This suggests that the
      arrangement of cistrons in a bicistronic setting is crucial for IRES-dependent
      translation of the second cistron. A systematic examination of expression of
      reporter cistrons from bicistronic mRNAs with respect to position was carried
      out. Using the dual luciferase assay system we show that the composition of
      reading frames on a bicistronic mRNA and the order in which they are arranged
      define the strength of IRES-dependent translation. Although the cellular
      environment and the nature of the IRES element influence translation strength the
      dominant determinant is the nature and the arrangement of cistrons on the mRNA.

PMID- 11504871
TI  - Characterization of Sp1, AP-1, CBF and KRC binding sites and minisatellite DNA as
      functional elements of the metastasis-associated mts1/S100A4 gene intronic
      enhancer.
AB  - The mts1/S100A4 gene encodes a small acidic calcium-binding protein that is
      expressed in a cell-specific manner in development, tumorigenesis and certain
      tissues of adult mice. A composite enhancer that is active in murine mammary
      adenocarcinoma cells was previously identified in the first intron of the
      mts1/S100A4 gene. Here we present a detailed analysis of the structure and
      function of this enhancer in the Mts1/S100A4-expressing CSML100 and non
      expressing CSML0 mouse adenocarcinoma cell lines. In CSML100 cells the enhancer
      activity is composed of at least six cis-elements interacting with Sp1 and AP-1
      family members and CBF/AML/PEBP2 and KRC transcription factors. In addition, a
      minisatellite-like DNA sequence significantly contributes to the enhancer
      activity via interaction with abundant proteins, which likely have been described
      previously under the name minisatellite-binding proteins. Extensive mutational
      analysis of the mts1/S100A4 enhancer revealed a cooperative function of KRC and
      the factors binding minisatellite DNA. This is the first example of an enhancer
      where two nuclear factors earlier implicated in different recombination processes
      cooperate to activate transcription. In Mts1/S100A4-negative CSML0 cells the
      strength of the enhancer was 7- to 12.5-fold lower compared to that in CSML100
      cells, when referred to the activities of three viral promoters. In CSML0 cells
      the enhancer could be activated by exogenous AP-1 and CBF transcription factors.

PMID- 11504872
TI  - SOX6 binds CtBP2 to repress transcription from the Fgf-3 promoter.
AB  - Fgf-3 is expressed in a complex pattern during mouse development. Previously, an
      essential regulatory element PS4A was identified in the promoter region, and
      shown to bind at least three factors. To identify the transcription factor(s), we
      used a yeast one-hybrid screen and obtained a novel Sox6 cDNA (SOX6D). When
      introduced into cells it strongly repressed activity from both an Fgf-3 reporter
      gene as well as an artificial promoter containing three PS4A elements. In situ
      hybridisation analysis showed that Sox6 and Fgf-3 are co-expressed in the otic
      vesicle of E9.5 mouse embryos in a mutually exclusive pattern, consistent with a
      repression of Fgf-3 transcription by SOX6. To characterise additional factor(s)
      involved in Fgf-3 gene repression, a yeast two-hybrid screen was used with the N
      terminal portion of SOX6D. Mouse CtBP2 cDNA clones were isolated and shown to
      bind SOX6 in yeast and mammalian cells. Furthermore, mutational analysis of SOX6
      showed that binding to CtBP2, and its responsiveness to this co-repressor, were
      dependent on a short amino acid sequence motif PLNLSS. Co-expression studies in
      NIH3T3 cells showed that SOX6 and CtBP2 co-operate to repress activity from the
      Fgf-3 promoter through the enhancer element PS4A. These results show that SOX6
      can recruit CtBP2 to repress transcription from the Fgf-3 promoter.

PMID- 11504873
TI  - The human growth hormone locus control region mediates long-distance
      transcriptional activation independent of nuclear matrix attachment regions.
AB  - Expression of the human growth hormone (hGH-N) transgene in the mouse pituitary
      is dependent on a multicomponent locus control region (LCR). The primary
      determinant of hGH LCR function maps to the pituitary-specific DNase I
      hypersensitive sites (HS) HSI,II, located 15 kb 5' to the hGH-N gene. The
      mechanism by which HSI,II mediates long-distance activation of the hGH locus
      remains undefined. Matrix attachment regions (MARs) comprise a set of AT-rich DNA
      elements postulated to interact with the nuclear scaffold and to mediate long
      distance interactions between LCR elements and their target promoters. Consistent
      with this model, sequence analysis strongly predicted a MAR determinant in close
      proximity to HSI,II. Surprisingly, cell-based analysis of nuclear scaffolds
      failed to confirm a MAR at this site, and extensive mapping demonstrated that the
      entire 87 kb region encompassing the hGH LCR and contiguous hGH gene cluster was
      devoid of MAR activity. Homology searches revealed that the predicted MAR
      reflected the recent insertion of a LINE 3'-UTR segment adjacent to HSI,II. These
      data point out discordance between sequence-based MAR predictions and in vivo MAR
      function and predict a novel MAR-independent mechanism for long-distance
      activation of hGH-N gene expression.

PMID- 11504874
TI  - Standard atomic volumes in double-stranded DNA and packing in protein--DNA
      interfaces.
AB  - Standard volumes for atoms in double-stranded B-DNA are derived using high
      resolution crystal structures from the Nucleic Acid Database (NDB) and compared
      with corresponding values derived from crystal structures of small organic
      compounds in the Cambridge Structural Database (CSD). Two different methods are
      used to compute these volumes: the classical Voronoi method, which does not
      depend on the size of atoms, and the related Radical Planes method which does.
      Results show that atomic groups buried in the interior of double-stranded DNA
      are, on average, more tightly packed than in related small molecules in the CSD.
      The packing efficiency of DNA atoms at the interfaces of 25 high resolution
      protein-DNA complexes is determined by computing the ratios between the volumes
      of interfacial DNA atoms and the corresponding standard volumes. These ratios are
      found to be close to unity, indicating that the DNA atoms at protein-DNA
      interfaces are as closely packed as in crystals of B-DNA. Analogous volume
      ratios, computed for buried protein atoms, are also near unity, confirming our
      earlier conclusions that the packing efficiency of these atoms is similar to that
      in the protein interior. In addition, we examine the number, volume and solvent
      occupation of cavities located at the protein-DNA interfaces and compared them
      with those in the protein interior. Cavities are found to be ubiquitous in the
      interfaces as well as inside the protein moieties. The frequency of solvent
      occupation of cavities is however higher in the interfaces, indicating that those
      are more hydrated than protein interiors. Lastly, we compare our results with
      those obtained using two different measures of shape complementarity of the
      analysed interfaces, and find that the correlation between our volume ratios and
      these measures, as well as between the measures themselves, is weak. Our results
      indicate that a tightly packed environment made up of DNA, protein and solvent
      atoms plays a significant role in protein-DNA recognition.

PMID- 11504875
TI  - N(omega)-arginine dimethylation modulates the interaction between a Gly/Arg-rich
      peptide from human nucleolin and nucleic acids.
AB  - We studied the interaction between a synthetic peptide (sequence Ac
      GXGGFGGXGGFXGGXGG-NH(2), where X = arginine, N(omega),N(omega)-dimethylarginine,
      DMA, or lysine) corresponding to residues 676-692 of human nucleolin and several
      DNA and RNA substrates using double filter binding, melting curve analysis and
      circular dichroism spectroscopy. We found that despite the reduced capability of
      DMA in forming hydrogen bonds, N(omega),N(omega)-dimethylation does not affect
      the strength of the binding to nucleic acids nor does it have any effect on
      stabilization of a double-stranded DNA substrate. However, circular dichroism
      studies show that unmethylated peptide can perturb the helical structure,
      especially in RNA, to a much larger extent than the DMA peptide.

PMID- 11504876
TI  - Human telomerase RNA-protein interactions.
AB  - Telomere length is maintained in most eukaryotic cells by telomerase. The core
      components of this ribonucleoprotein (RNP) enzyme include a protein catalytic
      subunit, composed of motifs conserved among reverse transcriptases (RT), and an
      RNA subunit that contains a short template sequence essential for the synthesis
      of telomeric repeats. We developed an electrophoretic mobility shift assay using
      active telomerase partially purified from 293 cells and radiolabeled, in vitro
      transcribed human telomerase RNA (hTR) to investigate the molecular interactions
      of the human telomerase RT (hTERT) and telomerase-associated proteins with hTR. A
      specific hTR-protein complex was identified and shown to contain hTERT and human
      Staufen by antibody supershift assays. Variants of hTR altered in distinct
      structural elements were analyzed for their ability to competitively inhibit
      complex formation. Human telomerase RNAs lacking the CR4-CR5 domain were poor
      inhibitors of hTR-protein complex formation, suggesting that the CR4-CR5 domain
      of hTR is a potential protein-binding site. Furthermore, alterations in the
      telomerase RNA pseudoknot's P3 helix, the CR7 domain, or the H/ACA box
      efficiently inhibited formation of the complex, indicating that these domains are
      dispensable for the assembly of a telomerase RNP in vitro. Potential telomerase
      associated proteins that bind hTR were also identified using a UV cross-linking
      assay.

PMID- 11504877
TI  - Effects of base change mutations within an Escherichia coli ribosomal RNA leader
      region on rRNA maturation and ribosome formation.
AB  - The effects of base change mutations in a highly conserved sequence (boxC) within
      the leader of bacterial ribosomal RNAs (rRNAs) was studied. The boxC sequence
      preceding the 16S rRNA structural gene constitutes part of the RNase III
      processing site, one of the first cleavage sites on the pathway to mature 16S
      rRNA. Moreover, rRNA leader sequences facilitate correct 16S rRNA folding,
      thereby assisting ribosomal subunit formation. Mutations in boxC cause cold
      sensitivity and result in 16S rRNA and 30S subunit deficiency. Strains in which
      all rRNA operons are replaced by mutant transcription units are viable.
      Thermodynamic studies by temperature gradient gel electrophoresis reveal that
      mutant transcripts have a different, less ordered structure. In addition, RNA
      secondary structure differences between mutant and wild-type transcripts were
      determined by chemical and enzymatic probing. Differences are found in the leader
      RNA sequence itself but also in structurally important regions of the mature 16S
      rRNA. A minor fraction of the rRNA transcripts from mutant operons is not
      processed by RNase III, resulting in a significantly extended precursor half-life
      compared to the wild-type. The boxC mutations also give rise to a new aberrant
      degradation product of 16S rRNA. This intermediate cannot be detected in strains
      lacking RNase III. Together the results indicate that the boxC sequence, although
      important for RNase III processing, is likely to serve additional functions by
      facilitating correct formation of the mature 16S rRNA structure. They also
      suggest that quality control steps are acting during ribosome biogenesis.

PMID- 11504878
TI  - Linked oligodeoxynucleotides show binding cooperativity and can selectively
      impair replication of deleted mitochondrial DNA templates.
AB  - Mutations in mitochondrial DNA (mtDNA) cause a spectrum of human pathologies,
      which predominantly affect skeletal muscle and the central nervous system. In
      patients, mutated and wild-type mtDNAs often co-exist in the same cell (mtDNA
      heteroplasmy). In the absence of pharmacological therapy, a genetic strategy for
      treatment has been proposed whereby replication of mutated mtDNA is inhibited by
      selective hybridisation of a nucleic acid derivative to the single-stranded
      replication intermediate, allowing propagation of the wild-type genome and
      correction of the associated respiratory chain defect. Previous studies have
      shown the efficacy of this anti-genomic approach in vitro, targeting pathogenic
      mtDNA templates with only a single point mutation. Pathogenic molecules
      harbouring deletions, however, present a more difficult problem. Deletions often
      occur at the site of two short repeat sequences (4-13 residues), only one of
      which is retained in the deleted molecule. With the more common larger repeats it
      is therefore difficult to design an anti-genomic molecule that will bind
      selectively across the breakpoint of the deleted mtDNA. To address this problem,
      we have used linker-substituted oligodeoxynucleotides to bridge the repeated
      residues. We show that molecules can be designed to bind more tightly to the
      deleted as compared to the wild-type mtDNA template, consistent with the
      nucleotide sequence on either side of the linker co-operating to increase binding
      affinity. Furthermore, these bridging molecules are capable of sequence-dependent
      partial inhibition of replication in vitro.

PMID- 11504879
TI  - Solution structure of an oligonucleotide containing an abasic site: evidence for
      an unusual deoxyribose conformation.
AB  - The antitumor antibiotic bleomycin causes two major lesions in the deoxyribose
      backbone of DNA: formation of 4'-keto abasic sites and formation of strand breaks
      with 3'-phosphoglycolate and 5'-phosphate ends. As a model for the 4'-keto abasic
      site, we have characterized an abasic site (X) in
      d(CCAAAGXACTGGG).d(CCCAGTACTTTGG) by two-dimensional NMR spectroscopy. A total of
      475 NOEs and 101 dihedral angles provided the restraints for molecular modeling.
      Four unusual NOEs were observed between each anomer of the abasic site and the
      neighboring bases. In addition, four coupling constants for adjacent protons of
      the deoxyribose of both the alpha and beta anomers of the abasic site were
      observed. The modeling suggests that for both anomers the abasic site is
      extrahelical, without significant distortion of the backbone opposite the lesion.
      The coupling constants further allowed assignment of an unusual sugar pucker for
      each anomer. The unique position of the abasic site in our structural model for
      each anomer is discussed in terms of repair of such lesions in vivo.

PMID- 11504880
TI  - Differential transcription of the orphan receptor RORbeta in nuclear extracts
      derived from Neuro2A and HeLa cells.
AB  - An important model system for studying the process leading to productive
      transcription is provided by the superfamily of nuclear receptors, which are for
      the most part ligand-controlled transcription factors. Over the past years
      several 'orphan' nuclear receptors have been isolated for which no ligand has yet
      been identified. Very little is known about how these 'orphan' receptors regulate
      transcription. In this study we have analysed the biochemical and transcriptional
      properties of the neuronally expressed orphan nuclear receptor RORbeta (NR1F2)
      and compared them with the retinoic acid receptor heterodimer RXRalpha-RARalpha
      (NR2B1-NR1B1) and Gal-VP16 in vitro. Although RORbeta binds to its DNA-binding
      sites with comparatively low affinity, it efficiently directs transcription in
      nuclear extracts derived from a neuronal cell line, Neuro2A, but not in nuclear
      extracts from non-neuronal HeLa cells. In contrast, RXRalpha-RARalpha and the
      acidic transcription factor Gal-VP16 support transcription in Neuro2A and HeLa
      nuclear extracts equally efficiently. These observations point to a different
      (co)factor requirement for transactivation by members of the NR1 subfamily of
      nuclear receptors.

PMID- 11504881
TI  - Methylglyoxal, an endogenous aldehyde, crosslinks DNA polymerase and the
      substrate DNA.
AB  - Methylglyoxal, a known endogenous and environmental mutagen, is a reactive alpha
      ketoaldehyde that can modify both DNA and proteins. To investigate the
      possibility that methylglyoxal induces a crosslink between DNA and DNA
      polymerase, we treated a 'primed template' DNA and the exonuclease-deficient
      Klenow fragment (KF(exo-)) of DNA polymerase I with methylglyoxal in vitro. When
      the reaction mixtures were analyzed by SDS-PAGE, we found that methylglyoxal
      induced a DNA-KF(exo-) crosslink. The specific binding complex of KF(exo-) and
      'primed template' DNA was necessary for formation of the DNA-KF(exo-) crosslink.
      Methylglyoxal reacted with guanine residues in the single-stranded portion of the
      template DNA. When 2'-deoxyguanosine was incubated with Nalpha-acetyllysine or N
      acetylcysteine in the presence of methylglyoxal, a crosslinked product was
      formed. No other amino acid derivatives tested could generate a crosslinked
      product. These results suggest that methylglyoxal crosslinks a guanine residue of
      the substrate DNA and lysine and cysteine residues near the binding site of the
      DNA polymerase during DNA synthesis and that DNA replication is severely
      inhibited by the methylglyoxal-induced DNA-DNA polymerase crosslink.

PMID- 11504882
TI  - Differential localization of HDAC4 orchestrates muscle differentiation.
AB  - The class II histone deacetylases HDAC4 and HDAC5 interact specifically with the
      myogenic MEF2 transcription factor and repress its activity. Here we show that
      HDAC4 is cytoplasmic during myoblast differentiation, but relocates to the
      nucleus once fusion has occurred. Inappropriate nuclear entry of HDAC4 following
      overexpression suppresses the myogenic programme as well as MEF2-dependent
      transcription. Activation of the Ca(2+)/calmodulin signalling pathway via
      constitutively active CaMKIV prevents nuclear entry of HDAC4 and HDAC4-mediated
      inhibition of differentiation. Consistent with a role of phosphorylation in HDAC4
      cytoplasmic localisation, HDAC4 binds to 14-3-3 proteins in a phosphorylation
      dependent manner. Together these data establish a role for HDAC4 in muscle
      differentiation. Recently, HDAC5 has also been implicated in muscle
      differentiation. However, despite the functional similarities of HDAC4 and HDAC5,
      their intracellular localisations are opposed, suggesting a distinct role for
      these enzymes during muscle differentiation.

PMID- 11504883
TI  - Enhancer activity of HS2 of the human beta-LCR is modulated by distance from the
      key nucleosome.
AB  - A class of curved DNA appears universally in eukaryotic genomic DNA at an average
      distance of approximately 680 bp and shows nucleosome positioning activity by
      having high affinity for histone core particles in an orientation- and position
      dependent manner. Here, we report that the enhancer activity at DNase I
      hypersensitive site 2 (HS2) of the human beta-globin locus control region (beta
      LCR) can be modulated by the curved DNA located at a distance of two nucleosomes
      from HS2 and that the nucleosome at the curved DNA regulates nearby nucleosome
      phases as a key nucleosome. Erythroid-specific nucleosome phases which caused
      deviation of the NF-E2 (p18-p45 dimer) binding site from the nucleosome dyad axis
      were over-represented when the distance between the key nucleosome and HS2
      exceeded 80 bp longer than the original length. At this state, enhancer activity
      was approximately 50% of that in the original construct, presumably due to
      reduced binding of transcription factors.

PMID- 11504884
TI  - Conditional cell ablation by stringent tetracycline-dependent regulation of
      barnase in mammalian cells.
AB  - Conditional expression of suicide genes in vivo has a wide range of applications
      in biological research and requires a minimal basal promoter activity in the
      uninduced state. To reduce basal activity of tetracycline (tc)-inducible target
      promoters we combined synthetic tet operators in varying numbers with a core
      promoter derived from the plant viral 35S promoter. An optimized promoter, P(TF),
      was found to exert a stringent regulation of luciferase in combination with tTA
      and rtTA in different mammalian cell lines. We linked P(TF) to the barnase gene,
      coding for a highly active RNase from Bacillus amyloliquefaciens. Stable cell
      clones expressing barnase under control of tTA exerted cell death only after tc
      withdrawal, correlating with a 10-fold induction of barnase mRNA expression.
      Directing tTA expression through a neuron-specific enolase promoter (P(NSE))
      leads to barnase expression and cell death in neuronal cells after tc withdrawal.
      Taken together, our data demonstrate that a stringent control of barnase
      expression in the uninduced state improves cell ablation studies, as high
      frequencies of transgene propagation in both cell lines and in transgenic mice
      are observed.

PMID- 11504885
TI  - Analysis of single nucleotide polymorphisms with solid phase invasive cleavage
      reactions.
AB  - Using microparticles as the capture surface and fluorescence resonance energy
      transfer as the detection technology, we have demonstrated the feasibility of
      performing the invasive cleavage reaction on a solid phase. An effective tool for
      many genomic applications, the solution phase invasive cleavage assay is a signal
      amplification method capable of distinguishing nucleic acids that differ by only
      a single base mutation. The method positions two overlapping oligonucleotides,
      the probe and upstream oligonucleotides, on the target nucleic acid to create a
      complex recognized and cleaved by a structure-specific 5'-nuclease. For
      microarray and other multiplex applications, however, the method must be adapted
      to a solid phase platform. Effective cleavage of the probe oligonucleotide
      occurred when either of the two required overlapping oligonucleotides was
      configured as the particle-bound reagent and also when both oligonucleotides were
      attached to the solid phase. Positioning probe oligonucleotides away from the
      particle surface via long tethers improved both the signal and the reaction
      rates. The particle-based invasive cleavage reaction was capable of
      distinguishing the ApoE Cys158 and Arg158 alleles at target concentrations as low
      as 100 amol/assay (0.5 pM).

PMID- 11504886
TI  - In vitro repair of complex unligatable oxidatively induced DNA double-strand
      breaks by human cell extracts.
AB  - We describe a new assay for in vitro repair of oxidatively induced DNA double
      strand breaks (DSBs) by HeLa cell nuclear extracts. The assay employs linear
      plasmid DNA containing DNA DSBs produced by the radiomimetic drug bleomycin. The
      bleomycin-induced DSB possesses a complex structure similar to that produced by
      oxidative processes and ionizing radiation. Bleomycin DSBs are composed of blunt
      ends or ends containing a single 5'-base overhang. Regardless of the 5'-end
      structure, all bleomycin-induced DSBs possess 3'-ends blocked by
      phosphoglycolate. Cellular extraction and initial end joining conditions for our
      assay were optimized with restriction enzyme-cleaved DNA to maximize ligation
      activity. Parameters affecting ligation such as temperature, time, ionic
      strength, ATP utilization and extract protein concentration were examined.
      Similar reactions were performed with the bleomycin-linearized substrate. In all
      cases, end-joined molecules ranging from dimers to higher molecular weight forms
      were produced and observed directly in agarose gels stained with Vistra Green and
      imaged with a FluorImager 595. This detection method is at least 50-fold more
      sensitive than ethidium bromide and permits detection of </=0.25 ng double
      stranded DNA per band in post-electrophoretically stained agarose gels.
      Consequently, our end-joining reaction requires </=100 ng substrate DNA and
      >/=50% conversion of substrate to product is achieved with simple substrates such
      as restriction enzyme-cleaved DNA. Using our assay we have observed a 6-fold
      lower repair rate and a lag in reaction initiation for bleomycin-induced DSBs as
      compared to blunt-ended DNA. Also, end joining reaction conditions are DSB end
      group dependent. In particular, bleomycin-induced DSB repair is considerably more
      sensitive to inhibition by increased ionic strength than repair of blunt-ended
      DNA.

PMID- 11504887
TI  - Real-time observation of a single DNA digestion by lambda exonuclease under a
      fluorescence microscope field.
AB  - A fluorescence microscopy technique has been developed to visualize the behavior
      of individual DNA and protein molecules. Real-time direct observation of a single
      DNA molecule can be used to investigate the dynamics of DNA-protein interactions,
      such as the DNA digestion reaction by lambda exonuclease. In conventional methods
      it is impossible to analyze the dynamics of an individual lambda exonuclease
      molecule on a DNA because they can only observe the average behavior of a number
      of exonuclease molecules. Observation of a single molecule, on the other hand,
      can reveal processivity and binding rate of an individual exonuclease molecule.
      To evaluate the dynamics of lambda exonuclease, a stained lambda DNA molecule
      with one biotinylated terminal was fixed on an avidin-coated coverslip and
      straightened using a d.c. electric field. Microscopic observation of digestion of
      a straightened DNA molecule by lambda exonuclease revealed that the DNA digestion
      rate was approximately 1000 bases/s and also demonstrated high processivity.

PMID- 11504888
TI  - Adenovirus-mediated Cre deletion of floxed sequences in primary mouse cells is an
      efficient alternative for studies of gene deletion.
AB  - This study evaluates the utility of Cre-expressing adenovirus for deletion of
      floxed genes in primary cells using primary murine hepatocytes. Adenovirus
      infection was very efficient, even at very low MOI (>95% infection at a MOI of 6)
      and did not reduce viability. High level LacZ expression was cytotoxic to
      hepatocytes but Cre expression had no effect on viability. Cre-mediated
      recombination was completed within a timespan that permits experimentation during
      primary culture (>95% recombination after 24 h), independently of the number of
      floxed alleles per cell. Recombination did not induce p53 or produce cytological
      nuclear abnormalities (even in polyploid cells). Contrary to expectation,
      deletion of DNA ligase 1 did not alter cell cycle progression, although Cre
      expression hastens entry to S phase from G(1), independently of the presence of
      floxed sequences. We conclude that adenovirus-mediated deletion of floxed alleles
      in primary cells is a straightforward and highly efficient tool for conducting
      preliminary studies of conditional gene targeting. Primary cells have advantages
      of differentiation, relative purity and ease of experimentation within controlled
      conditions, while avoiding confounding problems encountered in vivo (i.e. target
      cell specificity, kinetics and level of recombination, and elicitation of
      inflammatory and immune responses). This system could help identify important
      phenotypic effects and design and interpret in vivo studies.

PMID- 11504889
TI  - DNA monolayer on gold substrates characterized by nanoparticle labeling and
      scanning force microscopy.
AB  - Monolayers of single-stranded DNA on gold substrates were studied by scanning
      force microscopy. Complementary DNA probes labeled by gold nanoparticles were
      applied for contrast enhancement. Substrate regions modified with DNA could be
      visualized in a highly specific manner. The influence of the solution
      concentration on the surface density of adsorbed nanoparticles could be
      visualized. Because individual label particles can be easily detected, this
      labeling technique opens the way for characterization of DNA monolayers with a
      lateral resolution in the nanometer range.

PMID- 11504890
TI  - Chloroplast transit peptide prediction: a peek inside the black box.
AB  - Previous work in predicting protein localization to the chloroplast organelle in
      plants led to the development of an artificial neural network-based approach
      capable of remarkable accuracy in its prediction (ChloroP). A common criticism
      against such neural network models is that it is difficult to interpret the
      criteria that are used in making predictions. We address this concern with
      several new prediction methods that base predictions explicitly on the abundance
      of different amino acid types in the N-terminal region of the protein. Our
      successful prediction accuracy suggests that ChloroP uses little positional
      information in its decision-making; an unexpected result given the elaborate
      ChloroP input scheme. By removing positional information, our simpler methods
      allow us to identify those amino acids that are useful for successful prediction.
      The identification of important sequence features, such as amino acid content, is
      advantageous if one of the goals of localization predictors is to gain an
      understanding of the biological process of chloroplast localization. Our most
      accurate predictor combines principal component analysis and logistic regression.
      Web-based prediction using this method is available online at
      http://apicoplast.cis.upenn.edu/pclr/.

PMID- 11504891
TI  - Optimal conditions to use Pfu exo(-) DNA polymerase for highly efficient ligation
      mediated polymerase chain reaction protocols.
AB  - Ligation-Mediated Polymerase Chain Reaction (LMPCR) is the most sensitive
      sequencing technique available to map single-stranded DNA breaks at the
      nucleotide level of resolution using genomic DNA. LMPCR has been adapted to map
      DNA damage and reveal DNA-protein interactions inside living cells. However, the
      sequence context (GC content), the global break frequency and the current
      combination of DNA polymerases used in LMPCR affect the quality of the results.
      In this study, we developed and optimized an LMPCR protocol adapted for
      Pyrococcus furiosus exo(-) DNA polymerase (Pfu exo(-)). The relative efficiency
      of Pfu exo(-) was compared to T7-modified DNA polymerase (Sequenase 2.0) at the
      primer extension step and to Thermus aquaticus DNA polymerase (Taq) at the PCR
      amplification step of LMPCR. At all break frequencies tested, Pfu exo(-) proved
      to be more efficient than Sequenase 2.0. During both primer extension and PCR
      amplification steps, the ratio of DNA molecules per unit of DNA polymerase was
      the main determinant of the efficiency of Pfu exo(-), while the efficiency of Taq
      was less affected by this ratio. Substitution of NaCl for KCl in the PCR reaction
      buffer of Taq strikingly improved the efficiency of the DNA polymerase. Pfu exo(
      ) was clearly more efficient than Taq to specifically amplify extremely GC-rich
      genomic DNA sequences. Our results show that a combination of Pfu exo(-) at the
      primer extension step and Taq at the PCR amplification step is ideal for in vivo
      DNA analysis and DNA damage mapping using LMPCR.

PMID- 11504892
TI  - Multiplex polymerase chain reaction (PCR) with color-tagged module-shuffling
      primers for comparing gene expression levels in various cells.
AB  - A method based on the multiplex polymerase chain reaction (PCR) and gel
      electrophoresis for the comparative analysis of gene expression levels was
      developed. Using the method many cDNA fragments from different sources can be
      compared simultaneously. Competitive PCR amplification of expressed genes from
      different sources was performed by using 'module-shuffling primers' (MPSs). The
      MPSs (labeled with different fluorophores) consist of sequence modules of 3 or 4
      nt. The modules are arranged in different orders in each primer; therefore, the
      base sequences of the primers are different but their melting temperatures are
      identical. The genes expressed in different sources are ligated with tags
      complementary with the MPSs. Tag-ligated fragments are mixed in one tube and
      amplified at the same amplification efficiency by the MPSs. Amplified fragments
      are detected separately by multiple-color gel electrophoresis. This method can
      detect different amounts of each expressed gene, up to a difference in amounts of
      30%, and its detection limit is 0.1 amol per assay.

PMID- 11504893
TI  - The hybridization-stabilization assay: a solution-based isothermal method for
      rapid screening and determination of sequence preference of ligands that bind to
      duplexed nucleic acids.
AB  - The gene-to-drug quest will be most directly served by the discovery and
      development of small molecules that bind to nucleic acids and modulate gene
      expression at the level of transcription and/or inhibit replication of infectious
      agents. Full realization of this potential will require implementation of a
      complete suite of modern drug discovery technologies. Towards this end, here we
      describe our initial results with a new assay for identification and
      characterization of novel nucleic acid binding ligands. It is based on the well
      recognized property of stabilization of hybridization of complementary
      oligonucleotides by groove and/or intercalation binding ligands. Unlike
      traditional thermal melt methodologies, this assay is isothermal and, unlike gel
      based footprinting techniques, the assay also is performed in solution and
      detection can be by any number of highly sensitive, non-radioisotopic modalities,
      such as fluorescence resonance energy transfer, described herein. Thus, the assay
      is simple to perform, versatile in design and amenable to miniaturization and
      high throughput automation. Assay validation was performed using various
      permutations of direct and competitive binding formats and previously well
      studied ligands, including pyrrole polyamide and intercalator natural products,
      designed hairpin pyrrole-imidazole polyamides and furan-based non-polyamide
      dications. DNA specific ligands were identified and their DNA binding site size
      and sequence preference profiles were determined. A systematic approach to
      studying the relationship of binding sequence specificity with variation in
      ligand structure was demonstrated, and preferred binding sites in longer DNA
      sequences were found by pseudo-footprinting, with results that are in accord with
      established findings. This assay methodology should promote a more rapid
      discovery of novel nucleic acid ligands and potential drug candidates.

PMID- 11504894
TI  - Interdisciplinary approaches to adult orthodontic care.
AB  - The orthodontic treatment of adult patients is most frequently just one component
      of a more complex treatment involving several dental disciplines. This report
      discusses the potential problems related to the establishment of a treatment plan
      and the necessity for the patient's full acceptance, and understanding of the
      pros and cons related to different treatment approaches. In addition, the case
      report underlines the importance of a well-defined treatment goal. We have
      illustrated the team approach and the treatment principles in this combined perio
      , ortho-, and prosthodontic patient.

PMID- 11504895
TI  - Digital photography in orthodontics.
AB  - A brief history of digital photography is provided along with a critical
      appraisal of the 'prosumer' and professional systems currently available.
      Recommendations are made as to the system best suited to current orthodontic
      practice.

PMID- 11504896
TI  - A clinical investigation into the behaviour of crimpable archwire hooks.
AB  - The objective of this study was to measure the force applied to attach crimpable
      hooks securely to rectangular stainless steel archwires, both inside and outside
      the mouth. A specially designed strain gauge was utilized to measure the force
      applied by each operator. In vitro testing of the attached hooks was carried out
      using an Instron Universal Testing Machine. Two operators crimped a total of 80
      TP Orthodontic crimpable hooks to 0.019 x 0.025-inch stainless steel archwires.
      For one operator there was a significant difference between the intra- and extra
      oral forces used to produce firmly attached crimpable hooks (P = 0.03). However,
      in vitro testing demonstrated no statistically significant difference between the
      force levels required to displace the crimped hooks for either operator. The
      clinical significance of these findings is also discussed. Better reliability of
      crimpable hooks may be achieved by placing them out of the mouth.

PMID- 11504897
TI  - An ex vivo assessment of a resin-modified glass ionomer cement in relation to
      bonding technique.
AB  - OBJECTIVE: This study assessed a resin modified glass ionomer bonding system,
      Fuji ortho L.C. using different bonding techniques and compared it with a
      composite control (Transbond). DESIGN: Ex vivo study. Twenty extracted premolar
      teeth in each group were bonded as follows: (i) Group 1 Control (Transbond); (ii)
      Group 2 Fuji ortho L.C. without an etch procedure/wet enamel surface; (iii) Group
      3 Fuji ortho L.C. without an etch procedure/dry enamel surface; (iv) Group 4 Fuji
      ortho L.C. using a conventional acid etch technique. OUTCOME: Shear bond
      strength, site of bond failure and adhesive remnant index. RESULTS: Brackets
      bonded as recommended by the manufacturer (Group 2) have significantly (p <
      0.001) lower bond strengths compared with the control (Group 1). Bonding with an
      etch technique (Group 4) will significantly (p < 0.001) increase the bond
      strength compared with the other Fuji groups. All the Fuji groups tended to fail
      at the enamel/resin interface with lower ARI scores compared with the control.
      CONCLUSION: The lower bond strength of Fuji ortho L.C. would limit its use as a
      routine bonding agent. When bonded with an acid etch technique, the bond strength
      may be sufficient for low loading situations such as the upper anterior teeth.

PMID- 11504898
TI  - Craniofacial morphology of Japanese girls with Class II division 1 malocclusion.
AB  - OBJECTIVE: To identify the craniofacial features of Japanese girls with Class II
      division 1 malocclusions. METHOD: One hundred and ninety lateral cephalometric
      radiographs were analysed, and the subjects whose age ranged from 7 years 6
      months to 15 years 10 months were divided into three groups by their dentition:
      middle mixed dentition, late mixed dentition, and early permanent dentition. The
      mean values of 5 linear and 16 angular cephalometric parameters were compared
      with established Japanese Class I control values. RESULTS: Japanese girls with
      Class II division 1 malocclusion had a significantly small S-N-B angle (p <
      0.001), short mandibular ramus (p < 0.05-0.001), and a large mandibular plane
      angle (p < 0.05-0.001). CONCLUSION: Japanese girls with Class II division 1
      malocclusion had a high-angle facial pattern associated with the short mandibular
      ramus.

PMID- 11504899
TI  - Fluoride-releasing elastomeric modules reduce decalcification: a randomized
      controlled trial.
AB  - OBJECTIVE: To determine whether fluoride releasing elastomeric modules reduced
      the incidence of decalcification around orthodontic brackets during a complete
      course of orthodontic treatment. DESIGN: A randomised controlled, split mouth
      design. SETTING: The study was carried out in the orthodontic department of
      Newcastle-upon-Tyne Dental Hospital, UK. SUBJECT AND METHODS: 21 consecutive
      patients (126 teeth) undergoing fixed appliance therapy were studied. A split
      mouth technique was adopted to examine the upper labial segment, where one side
      (left or right) was randomly assigned to the experimental group, and the opposite
      side served as a control throughout their course of orthodontic treatment.
      INTERVENTIONS: The control teeth were ligated to the archwire using conventional
      modules. The experimental teeth were ligated to the archwire using Fluoride
      releasing elastomeric modules. OUTCOME MEASURES: Standardised photographs were
      taken of the upper labial segment before and after completion of orthodontic
      treatment, and the degree of decalcification assessed in each tooth quadrant,
      using a modification of the Enamel Defect Score. RESULTS: Decalcification was
      found to occur in both treatment groups, though to a significantly greater degree
      on the control side (p = 0.002). The fluoride module side showed significantly
      fewer serious decalcified lesions than the control (p = 0.013). No patients
      withdrew from the study. CONCLUSIONS: It would appear that the use of fluoride
      releasing elastomeric modules reduces the degree of decalcification experienced
      during orthodontic treatment.

PMID- 11504900
TI  - An evaluation of the reproducibility of landmark identification using scanned
      cephalometric images.
AB  - OBJECTIVE: A method of cephalometric analysis is described in which cephalometric
      x-rays were scanned using a flat-bed scanner and transparency hood. Then the
      image was displayed on a computer monitor for point identification and subsequent
      cephalometric analysis using dedicated software. The reproducibility of point
      identification using this method was compared with two other, commonly used,
      methods. MATERIAL AND METHODS: The study material comprised 25 lateral skull x
      rays taken as part of routine orthodontic assessment. Repeat cephalometric point
      identification was carried out on each x-ray using 3 methods: 1. On-screen
      digitization of the scanned bitmap image (Screenceph method). 2. Tracing followed
      by digitization of the identified points and 3. Direct digitization. RESULTS: For
      the 8 angular and 4 linear cephalometric measurements examined the Screenceph
      method compared favourably with the two conventional methods. The median
      difference between methods was 0.5 degrees and 0.2 mm. Using constructed
      Cartesian axes to examine the x, y discrepancy between repeat measurements and
      comparing Screenceph to tracing followed by digitization, there were significant
      differences in 3 instances at the 5% level and 2 instances at the 1% level. These
      differences represented median scores of 0.14 to 0.32 mm greater for Screenceph.
      Comparing Screenceph to direct digitization 15 significant differences out of the
      28 measurements were noted: six at the 5% level and 9 at the 1% level. The actual
      difference in median scores ranged from 0.2 mm to 0.53 mm. CONCLUSION: The
      results demonstrated that Screenceph is sufficiently accurate to use in a
      clinical setting but is not yet sufficiently exact for use in research projects
      owing to hardware limitations.

PMID- 11504901
TI  - The effects of in-office reconditioning on the morphology of slots and bases of
      stainless steel brackets and on the shear/peel bond strength.
AB  - OBJECTIVES: To compare the effect of five in-office bracket reconditioning
      methods on: (i) bracket slot width and interwing gap measurements; (ii) the
      appearance of the bracket bases under scanning electron microscope (SEM), and;
      (iii) shear/peel bond strength (SPBS). SETTING: Ex vivo study. METHOD: One
      hundred and twenty-five brackets were initially bonded and were divided into five
      experimental groups and reconditioning by the following methods: (i) adhesive
      grinding using green stone (Gp II); (ii) sandblasting (Gp III); (iii) direct
      flaming (Gp IV); (iv) using the BigJane machine (Gp V), and; (v) application of
      Buchman method (Gp VI). OUTCOMES: Distortion of the brackets. Scanning electron
      microscopy of three representative specimens from each group. The remaining
      brackets were rebonded, then shear/peel forces to failure were measured (SPBS).
      RESULTS: The ANOVA and multiple comparison test exhibited a statistical, but not
      clinical, significant increase in the bracket measurements of Group VI. There was
      a significant reduction (28%) in the SPBS of Group II. Under the SEM, the wire
      mesh structure was maintained; however, the amount of adhesive remnants greatly
      varied among the groups. CONCLUSIONS: Although none of the in-office
      reconditioning methods employed adversely affected the bracket base and/or the
      bracket measurements, reconditioning with a green stone was not effective.
      Sandblasting method and direct flaming are recommended because of simplicity and
      time-saving advantages.

PMID- 11504902
TI  - An ex vivo investigation into the use of a plasma arc lamp when using a visible
      light-cured composite and a resin-modified glass poly(alkenoate) cement in
      orthodontic bonding.
AB  - OBJECTIVE: To determine the usefulness of the plasma arc lamp in orthodontic
      bonding when used with both a light curable diacrylate and a resin modified glass
      poly(alkenoate) cement. DESIGN: Ex-vivo study. METHOD: 160 second premolar teeth
      were divided into 2 groups. 80 teeth had steel brackets bonded using Transbond XT
      and 80 were bonded using Fuji Ortho LC. One of four light curing regimes were
      used, with 20 specimens in each group: (i) 20 seconds curing with a halogen lamp;
      (ii) 1 second; (iii) 2 seconds or; (iv) 3 seconds with the plasma lamp. OUTCOMES:
      Shear bond tested to failure and the force to debond (N) and locus of bond
      failure recorded in each case. RESULTS: Force to debond increases in the case of
      both bonding materials as the curing time with the plasma lamp increases. The
      force to debond with 1 and 2 seconds with the plasma lamp was significantly lower
      in each case. In all instances the force to debond was lower in the case of the
      resin modified glass poly(alkenoate) cement specimens. Locus of bond failure was
      unaffected by the method and length of light curing and was generally mixed mode.
      CONCLUSIONS: Use of the plasma arc lamp in orthodontic bonding could result in
      significant time saving.

PMID- 11504904
TI  - An introduction to economic evaluation of health care.
AB  - Economic evaluation is an accepted method for the appraisal of health care
      programmes. Although it is used widely in medicine, its use in the field of
      dentistry has achieved popularity more recently. Economic evaluation in dentistry
      is likely to become increasingly important in the future and this paper
      introduces readers to some of the basic concepts.

PMID- 11504907
TI  - An inhibitor of mTOR reduces neoplasia and normalizes p70/S6 kinase activity in
      Pten+/- mice.
AB  - PTEN phosphatase acts as a tumor suppressor by negatively regulating the
      phosphoinositide 3-kinase (PI3K) signaling pathway. It is unclear which
      downstream components of this pathway are necessary for oncogenic transformation.
      In this report we show that transformed cells of PTEN(+/-) mice have elevated
      levels of phosphorylated Akt and activated p70/S6 kinase associated with an
      increase in proliferation. Pharmacological inactivation of mTOR/RAFT/FRAP reduced
      neoplastic proliferation, tumor size, and p70/S6 kinase activity, but did not
      affect the status of Akt. These data suggest that p70/S6K and possibly other
      targets of mTOR contribute significantly to tumor development and that inhibition
      of these proteins may be therapeutic for cancer patients with deranged PI3K
      signaling.

PMID- 11504908
TI  - Enhanced sensitivity of PTEN-deficient tumors to inhibition of FRAP/mTOR.
AB  - Recent evidence places the FRAP/mTOR kinase downstream of the phosphatidyl
      inositol 3-kinase/Akt-signaling pathway, which is up-regulated in multiple
      cancers because of loss of the PTEN tumor suppressor gene. We performed
      biological and biochemical studies to determine whether PTEN-deficient cancer
      cells are sensitive to pharmacologic inhibition of FRAP/mTOR by using the
      rapamycin derivative CCI-779. In vitro and in vivo studies of isogenic PTEN(+/+)
      and PTEN(-/-) mouse cells as well as human cancer cells with defined PTEN status
      showed that the growth of PTEN null cells was blocked preferentially by
      pharmacologic FRAP/mTOR inhibition. Enhanced tumor growth caused by constitutive
      activation of Akt in PTEN(+/+) cells also was reversed by CCI-779 treatment,
      indicating that FRAP/mTOR functions downstream of Akt in tumorigenesis. Loss of
      PTEN correlated with increased S6 kinase activity and phosphorylation of
      ribosomal S6 protein, providing evidence for activation of the FRAP/mTOR pathway
      in these cells. Differential sensitivity to CCI-779 was not explained by
      differences in biochemical blockade of the FRAP/mTOR pathway, because S6
      phosphorylation was inhibited in sensitive and resistant cell lines. These
      results provide rationale for testing FRAP/mTOR inhibitors in PTEN null human
      cancers.

PMID- 11504909
TI  - Regulation of plant growth by cytokinin.
AB  - Cytokinins are a class of plant-specific hormones that play a central role during
      the cell cycle and influence numerous developmental programs. Because of the lack
      of biosynthetic and signaling mutants, the regulatory roles of cytokinins are not
      well understood. We genetically engineered cytokinin oxidase expression in
      transgenic tobacco plants to reduce their endogenous cytokinin content. Cytokinin
      deficient plants developed stunted shoots with smaller apical meristems. The
      plastochrone was prolonged, and leaf cell production was only 3-4% that of wild
      type, indicating an absolute requirement of cytokinins for leaf growth. In
      contrast, root meristems of transgenic plants were enlarged and gave rise to
      faster growing and more branched roots. These results suggest that cytokinins are
      an important regulatory factor of plant meristem activity and morphogenesis, with
      opposing roles in shoots and roots.

PMID- 11504911
TI  - DNA binding induces dissociation of the multimeric form of HIV-1 integrase: a
      time-resolved fluorescence anisotropy study.
AB  - Self-assembly of HIV-1 integrase (IN) in solution has been studied previously by
      time-resolved fluorescence, using tryptophan anisotropy decay. This approach
      provides information on the size of macromolecules via the determination of
      rotational correlation times (theta). We have shown that, at submicromolar
      concentration, IN is characterized by a long rotational correlation time
      (theta(20 degrees C) = 90-100 ns) corresponding to a high-order oligomeric form,
      likely a tetramer. In the present work, we investigated the self-assembly
      properties of the DNA-bound IN by using three independent fluorophores. Under
      enzymatic assay conditions (10(-7) M IN, 2 x 10(-8) M DNA), using either
      fluorescein-labeled or fluorescent guanosine analog-containing oligonucleotides
      that mimic a viral end long terminal repeat sequence, we found that the DNA-IN
      complex was characterized by shorter theta(20 degrees C) values of 15.5-19.5 and
      23-27 ns, calculated from experiments performed at 25 degrees C and 37 degrees C,
      respectively. These results were confirmed by monitoring the Trp anisotropy decay
      as a function of the DNA substrate concentration: the theta of IN shifted from 90
      100 ns to lower values (<30 ns) upon increasing the DNA concentration. Again, the
      normalized theta(20 degrees C) values were significantly higher when monitored at
      37 degrees C as compared with 25 degrees C. These results indicate that upon
      binding the viral DNA end, the multimeric enzyme undergoes a dissociation, most
      likely into a homogeneous monomeric form at 25 degrees C and into a monomer-dimer
      equilibrium at 37 degrees C.

PMID- 11504910
TI  - Inhibition of prostate carcinogenesis in TRAMP mice by oral infusion of green tea
      polyphenols.
AB  - Development of effective chemopreventive agents against prostate cancer (CaP) for
      humans requires conclusive evidence of their efficacy in animal models that
      closely emulates human disease. The autochthonous transgenic adenocarcinoma of
      the mouse prostate (TRAMP) model, which spontaneously develops metastatic CaP, is
      one such model that mimics progressive forms of human disease. Employing male
      TRAMP mice, we show that oral infusion of a polyphenolic fraction isolated from
      green tea (GTP) at a human achievable dose (equivalent to six cups of green tea
      per day) significantly inhibits CaP development and increases survival in these
      mice. In two separate experiments, the cumulative incidence of palpable tumors at
      32 weeks of age in 20 untreated mice was 100% (20 of 20). In these mice, 95% (19
      of 20), 65% (13 of 20), 40% (8 of 20), and 25% (5 of 20) of the animals exhibited
      distant site metastases to lymph nodes, lungs, liver, and bone, respectively.
      However, 0.1% GTP (wt/vol) provided as the sole source of drinking fluid to TRAMP
      mice from 8 to 32 weeks of age resulted in (i) significant delay in primary tumor
      incidence and tumor burden as assessed sequentially by MRI, (ii) significant
      decrease in prostate (64%) and genitourinary (GU) (72%) weight, (iii) significant
      inhibition in serum insulin-like growth factor-I and restoration of insulin-like
      growth factor binding protein-3 levels, and (iv) marked reduction in the protein
      expression of proliferating cell nuclear antigen (PCNA) in the prostate compared
      with water-fed TRAMP mice. The striking observation of this study was that GTP
      infusion resulted in almost complete inhibition of distant site metastases.
      Furthermore, GTP consumption caused significant apoptosis of CaP cells, which
      possibly resulted in reduced dissemination of cancer cells, thereby causing
      inhibition of prostate cancer development, progression, and metastasis of CaP to
      distant organ sites.

PMID- 11504912
TI  - Notch1 confers a resistance to glucocorticoid-induced apoptosis on developing
      thymocytes by down-regulating SRG3 expression.
AB  - We previously have reported that SRG3 is required for glucocorticoid (GC)-induced
      apoptosis in the S49.1 thymoma cell line. Activation of Notch1 was shown to
      induce GC resistance in thymocytes. However, the specific downstream target of
      Notch1 that confers GC resistance on thymocytes is currently unknown. We found
      that the expression level of SRG3 was critical in determining GC sensitivity in
      developing thymocytes. The expression of SRG3 also was down-regulated by the
      activated form of Notch1 (NotchIC). The promoter activity of the SRG3 gene also
      was down-regulated by NotchIC. Expression of transgenic SRG3 resulted in the
      restoration of GC sensitivity in thymocytes expressing transgenic Notch1. These
      results suggest that SRG3 is the downstream target of Notch1 in regulating GC
      sensitivity of thymocytes.

PMID- 11504913
TI  - Partitioning of a polymer into a nanoscopic protein pore obeys a simple scaling
      law.
AB  - The dependence of the rate on polymer mass was examined for the reaction of four
      sulfhydryl-directed poly(ethylene glycol) reagents with cysteine residues located
      in the lumen of the staphylococcal alpha-hemolysin pore. The logarithms of the
      apparent rate constants for a particular site in the lumen were proportional to
      N, the number of repeat units in a polymer chain. The proportionality constant
      was -(a/D)(5/3), where a is the persistence length of the polymer ( approximately
      3.5A) and D is the diameter of the pore. Despite some incongruencies with the
      assumptions of the derivation, the result suggests that the polymers partition
      into the lumen of the pore according to the simple scaling law of Daoud and de
      Gennes, c(pore)/c(solution) = exp(-N(a/D)(5/3)). Therefore, the measured reaction
      rates yield an estimate of the diameter of the pore and might be applied to
      determine the approximate dimensions of cavities within other similar proteins.

PMID- 11504914
TI  - Mobilized bone marrow cells repair the infarcted heart, improving function and
      survival.
AB  - Attempts to repair myocardial infarcts by transplanting cardiomyocytes or
      skeletal myoblasts have failed to reconstitute healthy myocardium and coronary
      vessels integrated structurally and functionally with the remaining viable
      portion of the ventricular wall. The recently discovered growth and
      transdifferentiation potential of primitive bone marrow cells (BMC) prompted us,
      in an earlier study, to inject in the border zone of acute infarcts Lin(-) c
      kit(POS) BMC from syngeneic animals. These BMC differentiated into myocytes and
      vascular structures, ameliorating the function of the infarcted heart. Two
      critical determinants seem to be required for the transdifferentiation of
      primitive BMC: tissue damage and a high level of pluripotent cells. On this
      basis, we hypothesized here that BMC, mobilized by stem cell factor and
      granulocyte-colony stimulating factor, would home to the infarcted region,
      replicate, differentiate, and ultimately promote myocardial repair. We report
      that, in the presence of an acute myocardial infarct, cytokine-mediated
      translocation of BMC resulted in a significant degree of tissue regeneration 27
      days later. Cytokine-induced cardiac repair decreased mortality by 68%, infarct
      size by 40%, cavitary dilation by 26%, and diastolic stress by 70%. Ejection
      fraction progressively increased and hemodynamics significantly improved as a
      consequence of the formation of 15 x 10(6) new myocytes with arterioles and
      capillaries connected with the circulation of the unaffected ventricle. In
      conclusion, mobilization of primitive BMC by cytokines might offer a noninvasive
      therapeutic strategy for the regeneration of the myocardium lost as a result of
      ischemic heart disease and, perhaps, other forms of cardiac pathology.

PMID- 11504915
TI  - A phosphatidylinositol 3-kinase/Akt pathway promotes translocation of Mdm2 from
      the cytoplasm to the nucleus.
AB  - The Mdm2 oncoprotein promotes cell survival and cell cycle progression by
      inhibiting the p53 tumor suppressor protein. To regulate p53, Mdm2 must gain
      nuclear entry, and the mechanism that induces this is now identified. Mitogen
      induced activation of phosphatidylinositol 3-kinase (PI3-kinase) and its
      downstream target, the Akt/PKB serine-threonine kinase, results in
      phosphorylation of Mdm2 on serine 166 and serine 186. Phosphorylation on these
      sites is necessary for translocation of Mdm2 from the cytoplasm into the nucleus.
      Pharmacological blockade of PI3-kinase/Akt signaling or expression of dominant
      negative PI3-kinase or Akt inhibits nuclear entry of Mdm2, increases cellular
      levels of p53, and augments p53 transcriptional activity. Expression of
      constitutively active Akt promotes nuclear entry of Mdm2, diminishes cellular
      levels of p53, and decreases p53 transcriptional activity. Mutation of the Akt
      phosphorylation sites in Mdm2 produces a mutant protein that is unable to enter
      the nucleus and increases p53 activity. The demonstration that PI3-kinase/Akt
      signaling affects Mdm2 localization provides insight into how this pathway, which
      is inappropriately activated in many malignancies, affects the function of p53.

PMID- 11504916
TI  - Gene transfer of the JNK interacting protein-1 protects dopaminergic neurons in
      the MPTP model of Parkinson's disease.
AB  - Increasing evidence suggests that apoptosis may be the underlying cell death
      mechanism in the selective loss of dopaminergic neurons in Parkinson's disease.
      Because the inhibition of caspases provides only partial protection in the 1
      methyl-4-phenyl-1,2,3,6-tetrahydropyridine/1-methyl-4-phenylpyridinium
      (MPTP/MPP(+)) model of Parkinson's disease, we investigated the role of the
      proapoptotic c-Jun N-terminal kinase (JNK) signaling cascade in SH-SY5Y human
      neuroblastoma cells in vitro and in mice in vivo. MPTP/MPP(+) led to the
      sequential phosphorylation and activation of JNK kinase (MKK4), JNK, and c-Jun,
      the activation of caspases, and apoptosis. In mice, adenoviral gene transfer of
      the JNK binding domain of JNK-interacting protein-1 (a scaffold protein and
      inhibitor of JNK) inhibited this cascade downstream of MKK4 phosphorylation,
      blocked JNK, c-Jun, and caspase activation, the death of dopaminergic neurons,
      and the loss of catecholamines in the striatum. Furthermore, the gene transfer
      resulted in behavioral benefit. Therefore, inhibition of the JNK pathway offers a
      new treatment strategy for Parkinson's disease that blocks the death signaling
      pathway upstream of the execution of apoptosis in dopaminergic neurons, providing
      a therapeutic advantage over the direct inhibition of caspases.

PMID- 11504917
TI  - X-ray structure of sensory rhodopsin II at 2.1-A resolution.
AB  - Sensory rhodopsins (SRs) belong to a subfamily of heptahelical transmembrane
      proteins containing a retinal chromophore. These photoreceptors mediate the
      cascade of vision in animal eyes and phototaxis in archaebacteria and unicellular
      flagellated algae. Signal transduction by these photoreceptors occurs by means of
      transducer proteins. The two archaebacterial sensory rhodopsins SRI and SRII are
      coupled to the membrane-bound HtrI and HtrII transducer proteins. Activation of
      these proteins initiates phosphorylation cascades that modulate the flagellar
      motors, resulting in either attractant (SRI) or repellent (SRII) phototaxis. In
      addition, transducer-free SRI and SRII were shown to operate as proton pumps,
      analogous to bacteriorhodopsin. Here, we present the x-ray structure of SRII from
      Natronobacterium pharaonis (pSRII) at 2.1-A resolution, revealing a unique
      molecular architecture of the retinal-binding pocket. In particular, the
      structure of pSRII exhibits a largely unbent conformation of the retinal (as
      compared with bacteriorhodopsin and halorhodopsin), a hydroxyl group of Thr-204
      in the vicinity of the Schiff base, and an outward orientation of the guanidinium
      group of Arg-72. Furthermore, the structure reveals a putative chloride ion that
      is coupled to the Schiff base by means of a hydrogen-bond network and a unique,
      positively charged surface patch for a probable interaction with HtrII. The high
      resolution structure of pSRII provides a structural basis to elucidate the
      mechanisms of phototransduction and color tuning.

PMID- 11504918
TI  - CmC(A/T)GG DNA methylation in mature B cell lymphoma gene silencing.
AB  - DNA methylation has been linked to gene silencing in cancer. Primary effusion
      lymphoma (PEL) and myeloma are lymphoid malignancies that arise from terminally
      differentiated B cells. Interestingly, PEL do not express immunoglobulins or most
      B lineage-specific genes. The B cell-specific B29 (Igbeta/CD79b) gene is silenced
      in PEL and some myelomas but is expressed in other normal and malignant B cells.
      B29 expression was reactivated in PEL by demethylating and histone deacetylase
      inhibiting treatments. Bisulfite sequencing revealed two types of DNA methylation
      in silenced B29 promoters: at conventional CpG and at CC(A/T)GG B29 promoter
      sites. The pattern of methylated CpG ((m)CpG) and C(m)C(A/T)GG B29 promoter
      methylation observed was similar to that recently reported for epigenetic
      silencing of an integrated retrovirus. Methylation of C(m)C(A/T)GG sites in the
      B29 promoter significantly repressed in vivo transcriptional activity. Also,
      methylation of a central conserved C(m)CTGG B29 promoter site blocked the binding
      of early B cell factor. This methylated motif formed DNA-protein complexes with
      nuclear extracts from all cell types examined. Therefore, C(m)C(A/T)GG
      methylation may represent an important type of epigenetic marker on mammalian DNA
      that impacts transcription by altering DNA-protein complex formation.

PMID- 11504919
TI  - Intravenous administration of MEK inhibitor U0126 affords brain protection
      against forebrain ischemia and focal cerebral ischemia.
AB  - Brain subjected to acute ischemic attack caused by an arterial blockage needs
      immediate arterial recanalization. However, restoration of cerebral blood flow
      can cause tissue injury, which is termed reperfusion injury. It is important to
      inhibit reperfusion injury to achieve greater brain protection. Because oxidative
      stress has been shown to activate mitogen-activated protein kinases (MAPKs), and
      because oxidative stress contributes to reperfusion injury, MAPK may be a
      potential target to inhibit reperfusion injury after brain ischemia. Here, we
      demonstrate that reperfusion after forebrain ischemia dramatically increases
      phosphorylation level of extracellular signal-regulated kinase 2 (ERK2) in the
      gerbil hippocampus. In addition, i.v. administration of U0126 (100-200 mg/kg), a
      specific inhibitor of MEK (MAPK/ERK kinase), protects the hippocampus against
      forebrain ischemia. Moreover, treatment with U0126 at 3 h after ischemia
      significantly reduces infarct volume after transient (3 h) focal cerebral
      ischemia in mice. This protection is accompanied by reduced phosphorylation level
      of ERK2, substrates for MEK, in the damaged brain areas. Furthermore, U0126
      protects mouse primary cultured cortical neurons against oxygen deprivation for 9
      h as well as nitric oxide toxicity. These results provide further evidence for
      the role of MEK/ERK activation in brain injury resulting from
      ischemia/reperfusion, and indicate that MEK inhibition may increase the
      resistance of tissue to ischemic injury.

PMID- 11504920
TI  - Failed retrograde transport of NGF in a mouse model of Down's syndrome: reversal
      of cholinergic neurodegenerative phenotypes following NGF infusion.
AB  - Age-related degeneration of basal forebrain cholinergic neurons (BFCNs)
      contributes to cognitive decline in Alzheimer's disease and Down's syndrome. With
      aging, the partial trisomy 16 (Ts65Dn) mouse model of Down's syndrome exhibited
      reductions in BFCN size and number and regressive changes in the hippocampal
      terminal fields of these neurons with respect to diploid controls. The changes
      were associated with significantly impaired retrograde transport of nerve growth
      factor (NGF) from the hippocampus to the basal forebrain. Intracerebroventricular
      NGF infusion reversed well established abnormalities in BFCN size and number and
      restored the deficit in cholinergic innervation. The findings are evidence that
      even BFCNs chronically deprived of endogenous NGF respond to an intervention that
      compensates for defective retrograde transport. We suggest that age-related
      cholinergic neurodegeneration may be a treatable disorder of failed retrograde
      NGF signaling.

PMID- 11504921
TI  - FEZ1/LZTS1 gene at 8p22 suppresses cancer cell growth and regulates mitosis.
AB  - The FEZ1/LZTS1 gene maps to chromosome 8p22, a region that is frequently deleted
      in human tumors. Alterations in FEZ1/LZTS1 expression have been observed in
      esophageal, breast, and prostate cancers. Here, we show that introduction of
      FEZ1/LZTS1 into Fez1/Lzts1-negative cancer cells results in suppression of
      tumorigenicity and reduced cell growth with accumulation of cells at late S
      G(2)/M stage of the cell cycle. Fez1/Lzts1 protein is hyperphosphorylated by cAMP
      dependent kinase during cell-cycle progression. We found that Fez1/Lzts1 is
      associated with microtubule components and interacts with p34(cdc2) at late S
      G(2)/M stage in vivo. Present data show that FEZ1/LZTS1 inhibits cancer cell
      growth through regulation of mitosis, and that its alterations result in abnormal
      cell growth.

PMID- 11504922
TI  - TOUCHSTONE: an ab initio protein structure prediction method that uses threading
      based tertiary restraints.
AB  - The successful prediction of protein structure from amino acid sequence requires
      two features: an efficient conformational search algorithm and an energy function
      with a global minimum in the native state. As a step toward addressing both
      issues, a threading-based method of secondary and tertiary restraint prediction
      has been developed and applied to ab initio folding. Such restraints are derived
      by extracting consensus contacts and local secondary structure from at least
      weakly scoring structures that, in some cases, can lack any global similarity to
      the sequence of interest. Furthermore, to generate representative protein
      structures, a reduced lattice-based protein model is used with replica exchange
      Monte Carlo to explore conformational space. We report results on the application
      of this methodology, termed TOUCHSTONE, to 65 proteins whose lengths range from
      39 to 146 residues. For 47 (40) proteins, a cluster centroid whose rms deviation
      from native is below 6.5 (5) A is found in one of the five lowest energy
      centroids. The number of correctly predicted proteins increases to 50 when atomic
      detail is added and a knowledge-based atomic potential is combined with clustered
      and nonclustered structures for candidate selection. The combination of the ratio
      of the relative number of contacts to the protein length and the number of
      clusters generated by the folding algorithm is a reliable indicator of the
      likelihood of successful fold prediction, thereby opening the way for genome
      scale ab initio folding.

PMID- 11504923
TI  - HIV envelope gp120 activates human arterial smooth muscle cells.
AB  - There have been increasing reports of acute coronary thrombotic events in
      patients with HIV. Although these clinical events have been attributed primarily
      to dyslipidemia associated with protease inhibitor therapy, autopsy studies in
      children with HIV suggest the presence of an underlying arteriopathy. This study
      demonstrates that the HIV envelope protein, gp120, activates human arterial
      smooth muscle cells to express tissue factor, the initiator of the coagulation
      cascade. The induction of tissue factor by gp120 is mediated by two biologically
      relevant coreceptors for HIV infection, CXCR4 and CCR5, and is also dependent on
      the presence of functional CD4. Induction of tissue factor by gp120 requires
      activation of mitogen-activating protein kinases, activation of protein kinase C,
      and generation of reactive oxygen species, signaling pathways that have protean
      effects on smooth muscle cell physiology. The activation of smooth muscle cells
      by gp120 may play an important role in the vascular, thrombotic, and inflammatory
      responses to HIV infection.

PMID- 11504924
TI  - Molecular characterization of a mannoprotein with homology to chitin deacetylases
      that stimulates T cell responses to Cryptococcus neoformans.
AB  - The fungus Cryptococcus neoformans is a major cause of morbidity and mortality in
      patients with impaired CD4(+) T cell function, particularly those with AIDS. To
      identify cryptococcal antigens that could serve as vaccine candidates by
      stimulating T cell responses, C. neoformans-reactive CD4(+) T cell hybridomas
      were generated by immunization of C57BL/6 mice and fusion of splenocytes with
      thymoma cells. The antigen that stimulated one of the hybridomas, designated
      P1D6, to produce IL-2 was purified to homogeneity by sequential anion exchange
      chromatography, hydrophobic interaction chromatography, and SDS/PAGE. Based on
      its apparent molecular mass of 98 kDa and mannosylation, the antigen of interest
      was named MP98. MP98 was N terminal-sequenced, and the gene encoding the protein
      was cloned and sequenced. Recombinant MP98, expressed in Saccharomyces
      cerevisiae, stimulated P1D6 to produce IL-2. Analysis of the derived 458-aa
      sequence of MP98 reveals an N-terminal cleavable signal sequence, a
      polysaccharide deacetylase domain found in fungal chitin deacetylases, and a
      serine/threonine-rich C-terminal region. Overall, there were 103 serine/threonine
      residues serving as potential O-linked glycosylation sites as well as 12 possible
      N-linked glycosylation sites. Thus, a C. neoformans mannoprotein has been
      characterized that stimulates T cell responses and has molecular properties of a
      chitin deacetylase.

PMID- 11504925
TI  - Mutations in Mlph, encoding a member of the Rab effector family, cause the
      melanosome transport defects observed in leaden mice.
AB  - The d, ash, and ln coat color mutations provide a unique model system for the
      study of vesicle transport in mammals. All three mutant loci encode genes that
      are required for the polarized transport of melanosomes, the specialized, pigment
      containing organelles of melanocytes, to the neighboring keratinocytes and
      eventually into coat hairs. Genetic studies suggest that these genes function in
      the same or overlapping pathways and are supported by biochemical studies showing
      that d encodes an actin-based melanosome transport motor, MyoVa, whereas ash
      encodes Rab27a, a protein that localizes to the melanosome and is postulated to
      serve as the MyoVa receptor. Here we show that ln encodes melanophilin (Mlph), a
      previously undescribed protein with homology to Rab effectors such as
      granuphilin, Slp3-a, and rabphilin-3A. Like all of these effectors, Mlph
      possesses two Zn(2+)-binding CX(2)CX(13,14)CX(2)C motifs and a short aromatic
      rich amino acid region that is critical for Rab binding. However, Mlph does not
      contain the two Ca(2+)-binding C(2) domains found in these and other proteins
      involved in vesicle transport, suggesting that it represents a previously
      unrecognized class of Rab effectors. Collectively, our data show that Mlph is a
      critical component of the melanosome transport machinery and suggest that Mlph
      might function as part of a transport complex with Rab27a and MyoVa.

PMID- 11504926
TI  - Hemocytes are essential for wing maturation in Drosophila melanogaster.
AB  - Newly eclosed flies have wings that are highly folded and compact. Within an
      hour, each wing has expanded, the dorsal and ventral cuticular surfaces bonding
      to one another to form the mature wing. To initiate a dissection of this process,
      we present studies of two mutant phenotypes. First, the batone mutant blocks wing
      expansion, a behavior that is shown to have a mutant focus anterior to the wing
      in the embryonic fate map. Second, ectopic expression of protein kinase A
      catalytic subunit (PKAc) using certain GAL4 enhancer detector strains mimics the
      batone wing phenotype and also induces melanotic "tumors." Surprisingly, these
      GAL4 strains express GAL4 in cells, which seem to be hemocytes, found between the
      dorsal and ventral surfaces of newly opened wings. Ectopic expression of Ricin A
      in these cells reduces their number and prevents bonding of the wing surfaces
      without preventing wing expansion. We propose that hemocytes are present in the
      wing to phagocytose apoptotic epithelial cells and to synthesize an extracellular
      matrix that bonds the two wing surfaces together. Hemocytes are known to form
      melanotic tumors either as part of an innate immune response or under other
      abnormal conditions, including evidently ectopic PKAc expression. Ectopic
      expression of PKAc in the presence of the batone mutant causes dominant
      lethality, suggesting a functional relationship. We propose that batone is
      required for the release of a hormone necessary for wing expansion and tissue
      remodeling by hemocytes in the wing.

PMID- 11504927
TI  - HIV-1 induces phenotypic and functional perturbations of B cells in chronically
      infected individuals.
AB  - A number of perturbations of B cells has been described in the setting of HIV
      infection; however, most remain poorly understood. To directly address the effect
      of HIV replication on B cell function, we investigated the capacity of B cells
      isolated from HIV-infected patients to respond to a variety of stimuli before and
      after reduction of viremia by effective antiretroviral therapy. B cells taken
      from patients with high levels of plasma viremia were defective in their
      proliferative responses to various stimuli. Viremia was also associated with the
      appearance of a subpopulation of B cells that expressed reduced levels of CD21.
      After fractionation into CD21(high)- and CD21(low)-expressing B cells, the
      CD21(low) fraction showed dramatically reduced proliferation in response to B
      cell stimuli and enhanced secretion of immunoglobulins when compared with the
      CD21(high) fraction. Electron microscopic analysis of each fraction revealed
      cells with plasmacytoid features in the CD21(low) B cell population but not in
      the CD21(high) fraction. These results indicate that HIV viremia induces the
      appearance of a subset of B cells whose function is impaired and which may be
      responsible for the hypergammaglobulinemia associated with HIV disease.

PMID- 11504928
TI  - Self-organization of a radial microtubule array by dynein-dependent nucleation of
      microtubules.
AB  - Polarized radial arrays of cytoplasmic microtubules (MTs) with minus ends
      clustered at the cell center define the organization of the cytoplasm through
      interaction with microtubule motors bound to membrane organelles or chromosomes.
      It is generally assumed that the radial organization results from nucleation of
      MTs at the centrosome. However, radial MT array can also be attained through self
      organization that requires the activity of a minus-end-directed MT motor,
      cytoplasmic dynein. In this study we examine the role of cytoplasmic dynein in
      the self-organization of a radial MT array in cytoplasmic fragments of fish
      melanophores lacking the centrosome. After activation of dynein motors bound to
      membrane-bound organelles, pigment granules, the fragments rapidly form polarized
      radial arrays of MTs and position pigment aggregates at their centers. We show
      that rearrangement of MTs in the cytoplasm is achieved through dynein-dependent
      MT nucleation. The radial pattern is generated by continuous disassembly and
      reassembly of MTs and concurrent minus-end-directed transport of pigment granules
      bearing the nucleation sites.

PMID- 11504929
TI  - Basolateral membrane expression of a K+ channel, Kir 2.3, is directed by a
      cytoplasmic COOH-terminal domain.
AB  - The inwardly rectifying potassium channel Kir 2.3 is specifically targeted and
      expressed on the basolateral membrane of certain renal epithelial cells. In the
      present study, the structural basis for polarized targeting was elucidated.
      Deletion of a unique COOH-terminal domain produced channels that were mistargeted
      to the apical membrane, consistent with the removal of a basolateral membrane
      sorting signal. By characterizing a series of progressively smaller truncation
      mutants, an essential targeting signal was defined (residues 431-442) within a
      domain that juxtaposes or overlaps with a type I PDZ binding motif (442). Fusion
      of the COOH-terminal structure onto CD4 was sufficient to change a random
      membrane-trafficking and expression pattern into a basolateral membrane one.
      Using metabolic labeling and pulse-chase and surface immunoprecipitation, we
      found that CD4-Kir2.3 COOH-terminal chimeras were rapidly and directly targeted
      to the basolateral membrane, consistent with a sorting signal that is processed
      in the biosynthetic pathway. Collectively, the data indicate that the basolateral
      sorting determinant in Kir 2.3 is composed of a unique arrangement of trafficking
      motifs, containing tandem, conceivably overlapping, biosynthetic targeting and
      PDZ-based signals. The previously unrecognized domain corresponds to a highly
      degenerate structure within the Kir channel family, raising the possibility that
      the extreme COOH terminus of Kir channels may differentially coordinate membrane
      targeting of different channel isoforms.

PMID- 11504932
TI  - Do mRNAs act as direct sensors of small molecules to control their expression?

PMID- 11504933
TI  - Multidisciplinary dissection of behavioral arousal: The role of muscarinic
      acetylcholine stimulation in grasshopper stridulatory behavior.

PMID- 11504934
TI  - Flotillas of lipid rafts fore and aft.

PMID- 11504935
TI  - Following the trace of elusive amines.

PMID- 11504937
TI  - Aggregate sound velocities and acoustic Gruneisen parameter of iron up to 300 GPa
      and 1,200 K.
AB  - Successful interpretation of available geophysical data requires experimental and
      theoretical information on the elasticity of solids under physical conditions of
      Earth's interior. Because iron is considered as major component in Earth's core,
      elastic properties of iron at high pressures and temperatures are very important
      for modeling its composition and dynamics. We use in situ x-ray diffraction data
      on epsilon-iron at static pressures up to 300 GPa and temperatures to 1,200 K to
      determine the Debye-Waller temperature factors and calculate aggregate sound
      velocities and Gruneisen parameter of epsilon-iron by using an approach that is
      based on Rietveld refinement at high pressures and temperatures.

PMID- 11504936
TI  - Interchain hydrogen-bonding interactions may facilitate translocation of K+ ions
      across the potassium channel selectivity filter, as suggested by synthetic
      modeling chemistry.
AB  - A 4-fold symmetric arrangement of TVGYG polypeptides forms the selectivity filter
      of the K+ channel from Streptomyces lividans (KcsA). We report the synthesis and
      properties of synthetic models for the filter, p-tert-butyl-calix[4]arene
      (OCH(2)CO-XOBz)(4) (X = V, VG, VGY), 1-3. The first cation (Na+, K+) binds to the
      four -[OCH(2)CO]- units, a region devised to mimic the metal-binding site formed
      by the four T residues in KcsA. NMR studies reveal that cations and valine amide
      protons compete for the carbonyl oxygen atoms, converting NH(Val)...O=C hydrogen
      bonds to M+ ...O=C bonds (M+ = Na+ or K+). The strength of these interchain
      NH(Val)...O=C hydrogen bonds varies in the order 3 > 2 > 1. We propose that such
      interchain H-bonding may destabilize metal binding in the selectivity filter and
      thus help create the low energy barrier needed for rapid cation translocation.

PMID- 11504938
TI  - Quantum optical implementation of Grover's algorithm.
AB  - We present a scheme for a quantum optical implementation of Grover's algorithm
      based on resonant atomic interactions with classical fields and dispersive
      couplings with quantized cavity fields. The proposed scheme depends on
      preparation of entangled states and is within current state-of-the-art
      technology.

PMID- 11504939
TI  - Characterization of an adapter subunit to a phosphatidylinositol (3)P 3
      phosphatase: identification of a myotubularin-related protein lacking catalytic
      activity.
AB  - The D3-phosphoinositides act as second messengers by recruiting, and thereby
      activating, diverse signaling proteins. We have previously described the
      purification of a rat phosphatidylinositol 3-phosphate [PtdIns(3)P] 3
      phosphatase, comprising a heterodimer of a 78-kDa adapter subunit in complex with
      a 65-kDa catalytic subunit. Here, we have cloned and characterized the cDNA
      encoding the human 3-phosphatase adapter subunit (3-PAP). Sequence alignment
      showed that 3-PAP shares significant sequence similarity with the protein and
      lipid 3-phosphatase myotubularin, and with several other members of the
      myotubularin gene family including SET-binding factor 1. However, unlike
      myotubularin, 3-PAP does not contain a consensus HCX(5)R catalytic motif. The 3
      PAP sequence contains several motifs that predict interaction with proteins
      containing Src homology-2 (SH2) domains, phosphotyrosine-binding (PTB) domains,
      members of the 14-3-3 family, as well as proteins with SET domains. Northern blot
      analysis identified two transcripts (5.5 kb and 2.5 kb) with highest abundance in
      human liver, kidney, lung, and placenta. 3-PAP immunoprecipitates isolated from
      platelet cytosol hydrolyzed the D3-phosphate from PtdIns(3)P and PtdIns 3,4
      bisphosphate [PtdIns(3,4)P(2)]. However, insect cell-expressed 3-PAP recombinant
      protein was catalytically inactive, confirming our prior prediction that this
      polypeptide represents an adapter subunit.

PMID- 11504940
TI  - Propagating conformational changes over long (and short) distances in proteins.
AB  - The problem of the propagation of conformational changes over long distances or
      through a closely packed protein is shown to fit a model of a ligand-induced
      conformational change between two protein states selected by evolution. Moreover,
      the kinetics of the pathway between these states is also selected so that the
      energy of ligand binding and the speed of the transition between conformational
      states are physiologically appropriate. The crystallographic data of a wild-type
      aspartate receptor that has negative cooperativity and a mutant that has no
      cooperativity but has native transmembrane signaling are shown to support this
      model.

PMID- 11504941
TI  - A Drosophila PIAS homologue negatively regulates stat92E.
AB  - Transcriptional activation by, and therefore the physiologic impact of, activated
      tyrosine-phosphorylated STATs (signal transducers and activators of
      transcription) may be negatively regulated by proteins termed PIAS (protein
      inhibitors of activated stats), as shown by previous experiments with mammalian
      cells in culture. Here, by using the genetic modifications in Drosophila, we
      demonstrate the in vivo functional interaction of the Drosophila homologues
      stat92E and a Drosophila PIAS gene (dpias). To this end we use a LOF allele and
      conditionally overexpressed dpias in JAK-STAT pathway mutant backgrounds. We
      conclude that the correct dpias/stat92E ratio is crucial for blood cell and eye
      development.

PMID- 11504942
TI  - HIF-1alpha binding to VHL is regulated by stimulus-sensitive proline
      hydroxylation.
AB  - Hypoxia-inducible factor-1alpha (HIF-1alpha) is a global transcriptional
      regulator of the hypoxic response. Under normoxic conditions, HIF-1alpha is
      recognized by the von Hippel-Lindau tumor-suppressor protein (VHL), a component
      of an E3 ubiquitin ligase complex. This interaction thereby promotes the rapid
      degradation of HIF-1alpha. Under hypoxic conditions, HIF-1alpha is stabilized. We
      have previously shown that VHL binds in a hypoxia-sensitive manner to a 27-aa
      segment of HIF-1alpha, and that this regulation depends on a posttranslational
      modification of HIF-1alpha. Through a combination of in vivo
      coimmunoprecipitation assays using VHL and a panel of point mutants of HIF-1alpha
      in this region, as well as MS and in vitro binding assays, we now provide
      evidence that this modification, which occurs under normoxic conditions, is
      hydroxylation of Pro-564 of HIF-1alpha. The data furthermore show that this
      proline hydroxylation is the primary regulator of VHL binding.

PMID- 11504943
TI  - Apaf-1 deficiency and neural tube closure defects are found in fog mice.
AB  - The forebrain overgrowth mutation (fog) was originally described as a spontaneous
      autosomal recessive mutation mapping to mouse chromosome 10 that produces
      forebrain defects, facial defects, and spina bifida. Although the fog mutant has
      been characterized and available to investigators for several years, the
      underlying mutation causing the pathology has not been known. Because of its
      phenotypic resemblance to apoptotic protease activating factor-1 (Apaf-1)
      knockout mice, we have investigated the possibility that the fog mutation is in
      the Apaf-1 gene. Allelic complementation, Western blot analysis, and caspase
      activation assays indicate that fog mutant mice lack Apaf-1 activity. Northern
      blot and reverse transcription-PCR analysis show that Apaf-1 mRNA is aberrantly
      processed, resulting in greatly reduced expression levels of normal Apaf-1 mRNA.
      These findings are strongly suggestive of the fog mutation being a hypomorphic
      Apaf-1 defect and implicate neural progenitor cell death in the pathogenesis of
      spina bifida-a common human congenital malformation. Because a complete
      deficiency in Apaf-1 usually results in perinatal lethality and fog/fog mice more
      readily survive into adulthood, these mutants serve as a valuable model with
      which apoptotic cell death can be studied in vivo.

PMID- 11504944
TI  - Evaluating hypotheses of basal animal phylogeny using complete sequences of large
      and small subunit rRNA.
AB  - We studied the evolutionary relationships among basal metazoan lineages by using
      complete large subunit (LSU) and small subunit (SSU) ribosomal RNA sequences for
      23 taxa. After identifying competing hypotheses, we performed maximum likelihood
      searches for trees conforming to each hypothesis. Kishino-Hasegawa tests were
      used to determine whether the data (LSU, SSU, and combined) reject any of the
      competing hypotheses. We also conducted unconstrained tree searches, compared the
      resulting topologies, and calculated bootstrap indices. Shimodaira-Hasegawa tests
      were applied to determine whether the data reject any of the topologies resulting
      from the constrained and unconstrained tree searches. LSU, SSU, and the combined
      data strongly contradict two assertions pertaining to sponge phylogeny.
      Hexactinellid sponges are not likely to be the basal lineage of a monophyletic
      Porifera or the sister group to all other animals. Instead, Hexactinellida and
      Demospongia form a well-supported clade of siliceous sponges, Silicea. It remains
      unclear, on the basis of these data alone, whether the calcarean sponges are more
      closely related to Silicea or to nonsponge animals. The SSU and combined data
      reject the hypothesis that Bilateria is more closely related to Ctenophora than
      it is to Cnidaria, whereas LSU data alone do not refute either hypothesis. LSU
      and SSU data agree in supporting the monophyly of Bilateria, Cnidaria,
      Ctenophora, and Metazoa. LSU sequence data reveal phylogenetic structure in a
      data set with limited taxon sampling. Continued accumulation of LSU sequences
      should increase our understanding of animal phylogeny.

PMID- 11504945
TI  - An Eulerian path approach to DNA fragment assembly.
AB  - For the last 20 years, fragment assembly in DNA sequencing followed the "overlap
      layout-consensus" paradigm that is used in all currently available assembly
      tools. Although this approach proved useful in assembling clones, it faces
      difficulties in genomic shotgun assembly. We abandon the classical "overlap
      layout-consensus" approach in favor of a new euler algorithm that, for the first
      time, resolves the 20-year-old "repeat problem" in fragment assembly. Our main
      result is the reduction of the fragment assembly to a variation of the classical
      Eulerian path problem that allows one to generate accurate solutions of large
      scale sequencing problems. euler, in contrast to the celera assembler, does not
      mask such repeats but uses them instead as a powerful fragment assembly tool.

PMID- 11504946
TI  - Treatment of spinal muscular atrophy by sodium butyrate.
AB  - Spinal muscular atrophy (SMA) is an autosomal recessive disease characterized by
      degeneration of the anterior horn cells of the spinal cord, leading to muscular
      paralysis with muscular atrophy. No effective treatment of this disorder is
      presently available. Studies of the correlation between disease severity and the
      amount of survival motor neuron (SMN) protein have shown an inverse relationship.
      We report that sodium butyrate effectively increases the amount of exon 7
      containing SMN protein in SMA lymphoid cell lines by changing the alternative
      splicing pattern of exon 7 in the SMN2 gene. In vivo, sodium butyrate treatment
      of SMA-like mice resulted in increased expression of SMN protein in motor neurons
      of the spinal cord and resulted in significant improvement of SMA clinical
      symptoms. Oral administration of sodium butyrate to intercrosses of heterozygous
      pregnant knockout-transgenic SMA-like mice decreased the birth rate of severe
      types of SMA-like mice, and SMA symptoms were ameliorated for all three types of
      SMA-like mice. These results suggest that sodium butyrate may be an effective
      drug for the treatment of human SMA patients.

PMID- 11504947
TI  - An immune response manifested by the common occurrence of annexins I and II
      autoantibodies and high circulating levels of IL-6 in lung cancer.
AB  - The identification of circulating tumor antigens or their related autoantibodies
      provides a means for early cancer diagnosis as well as leads for therapy. The
      purpose of this study was to identify proteins that commonly induce a humoral
      response in lung cancer by using a proteomic approach and to investigate
      biological processes that may be associated with the development of
      autoantibodies. Aliquots of solubilized proteins from a lung adenocarcinoma cell
      line (A549) and from lung tumors were subjected to two-dimensional PAGE, followed
      by Western blot analysis in which individual sera were tested for primary
      antibodies. Sera from 54 newly diagnosed patients with lung cancer and 60
      patients with other cancers and from 61 noncancer controls were analyzed. Sera
      from 60% of patients with lung adenocarcinoma and 33% of patients with squamous
      cell lung carcinoma but none of the noncancer controls exhibited IgG-based
      reactivity against proteins identified as glycosylated annexins I and/or II.
      Immunohistochemical analysis showed that annexin I was expressed diffusely in
      neoplastic cells in lung tumor tissues, whereas annexin II was predominant at the
      cell surface. Interestingly, IL-6 levels were significantly higher in sera of
      antibody-positive lung cancer patients compared with antibody-negative patients
      and controls. We conclude that an immune response manifested by annexins I and II
      autoantibodies occurs commonly in lung cancer and is associated with high
      circulating levels of an inflammatory cytokine. The proteomic approach we have
      implemented has utility for the development of serum-based assays for cancer
      diagnosis as we report in this paper on the discovery of antiannexins I and/or II
      in sera from patients with lung cancer.

PMID- 11504948
TI  - Acridine and phenothiazine derivatives as pharmacotherapeutics for prion disease.
AB  - Prion diseases in humans and animals are invariably fatal. Prions are composed of
      a disease-causing isoform (PrP(Sc)) of the normal host prion protein (PrP(C)) and
      replicate by stimulating the conversion of PrP(C) into nascent PrP(Sc). We report
      here that tricyclic derivatives of acridine and phenothiazine exhibit half
      maximal inhibition of PrP(Sc) formation at effective concentrations (EC(50))
      between 0.3 microM and 3 microM in cultured cells chronically infected with
      prions. The EC(50) for chlorpromazine was 3 microM, whereas quinacrine was 10
      times more potent. A variety of 9-substituted, acridine-based analogues of
      quinacrine were synthesized, which demonstrated variable antiprion potencies
      similar to those of chlorpromazine and emphasized the importance of the side
      chain in mediating the inhibition of PrP(Sc) formation. Thus, our studies show
      that tricyclic compounds with an aliphatic side chain at the middle ring moiety
      constitute a new class of antiprion reagents. Because quinacrine and
      chlorpromazine have been used in humans for many years as antimalarial and
      antipsychotic drugs, respectively, and are known to pass the blood-brain barrier,
      we suggest that they are immediate candidates for the treatment of Creutzfeldt
      Jakob disease and other prion diseases.

PMID- 11504949
TI  - A new recommended dietary allowance of vitamin C for healthy young women.
AB  - The recently released Recommended Dietary Allowance of vitamin C for women, 75 mg
      daily, was based on data for men. We now report results of a depletion-repletion
      study with healthy young women hospitalized for 186 +/- 28 days, using vitamin C
      doses of 30-2,500 mg daily. The relationship between dose and steady-state plasma
      concentration was sigmoidal. Only doses above 100 mg were beyond the linear
      portion of the curve. Plasma and circulating cells saturated at 400 mg daily,
      with urinary elimination of higher doses. Biomarkers of endogenous oxidant
      stress, plasma and urine F(2)-isoprostanes, and urine levels of a major
      metabolite of F(2)-isoprostanes were unchanged by vitamin C at all doses,
      suggesting this vitamin does not alter endogenous lipid peroxidation in healthy
      young women. By using Food and Nutrition Board guidelines, the data indicate that
      the Recommended Dietary Allowance for young women should be increased to 90 mg
      daily.

PMID- 11504950
TI  - A neurohistochemical blueprint for pain-induced loss of appetite.
AB  - A common complaint among pain patients is that they lose their appetite. These
      accounts are anecdotal, however, and the neural mechanism underlying pain-induced
      loss of appetite remains unknown. In this study, we documented the occurrence of
      appetite loss in patients under migraine attack and investigated the neuronal
      substrate of pain-induced anorexia in our animal model of intracranial pain. We
      found that loss of appetite during the migraine attack in humans coincided
      strongly with the onset and duration of the head pain in 32/39 cases, and that
      brief noxious stimulation of the dura in conscious rats produced a transient
      suppression of food intake. Mapping of neuronal activation in the rat showed that
      noxious dural stimulation induced a 3- to 4-fold increase in the number of Fos
      positive neurons in medullary dorsal horn areas that process nociceptive signals
      (laminae I, V) and in parabrachial and hypothalamic neurons positioned to
      suppress feeding behavior. In the parabrachial area, activated neurons were
      localized in the superior-lateral subnucleus, and 40% of them expressed the mRNA
      encoding the anorectic neuropeptide cholecystokinin. In the hypothalamus,
      activated Fos-positive neurons were found in the dorsomedial area of the
      ventromedial nucleus, and 76% of them expressed the mRNA for cholecystokinin type
      B receptor. Based on these findings, we suggest that at least one of several
      groups of hypothalamic neurons that normally inhibit appetite in response to
      metabolic cues is positioned to mediate the suppression of food intake by pain
      signals.

PMID- 11504951
TI  - Subretinal transplantation of genetically modified human cell lines attenuates
      loss of visual function in dystrophic rats.
AB  - Royal College of Surgeons rats are genetically predisposed to undergo significant
      visual loss caused by a primary dysfunction of retinal pigment epithelial (RPE)
      cells. By using this model, we have examined the efficacy of subretinal
      transplantation of two independent human RPE cell lines each exhibiting genetic
      modifications that confer long-term stability in vitro. The two cell lines, a
      spontaneously derived cell line (ARPE19) and an extensively characterized
      genetically engineered human RPE cell line (h1RPE7), which expresses SV40 large T
      (tumor) antigen, were evaluated separately. Both lines result in a significant
      preservation of visual function as assessed by either behavioral or physiological
      techniques. This attenuation of visual loss correlates with photoreceptor
      survival and the presence of donor cells in the areas of rescued photoreceptors
      at 5 months postgrafting (6 months of age). These results demonstrate the
      potential of genetically modified human RPE cells for ultimate application in
      therapeutic transplantation strategies for retinal degenerative diseases caused
      by RPE dysfunction.

PMID- 11504952
TI  - Mediation of tubuloglomerular feedback by adenosine: evidence from mice lacking
      adenosine 1 receptors.
AB  - Adenosine is a determinant of metabolic control of organ function increasing
      oxygen supply through the A2 class of adenosine receptors and reducing oxygen
      demand through A1 adenosine receptors (A1AR). In the kidney, activation of A1AR
      in afferent glomerular arterioles has been suggested to contribute to
      tubuloglomerular feedback (TGF), the vasoconstriction elicited by elevations in
      [NaCl] in the macula densa region of the nephron. To further elucidate the role
      of A1AR in TGF, we have generated mice in which the entire A1AR coding sequence
      was deleted by homologous recombination. Homozygous A1AR mutants that do not
      express A1AR mRNA transcripts and do not respond to A1AR agonists are viable and
      without gross anatomical abnormalities. Plasma and urinary electrolytes were not
      different between genotypes. Likewise, arterial blood pressure, heart rates, and
      glomerular filtration rates were indistinguishable between A1AR(+/+), A1AR(+/-),
      and A1AR(-/-) mice. TGF responses to an increase in loop of Henle flow rate from
      0 to 30 nl/min, whether determined as change of stop flow pressure or early
      proximal flow rate, were completely abolished in A1AR(-/-) mice (stop flow
      pressure response, -6.8 +/- 0.55 mmHg and -0.4 +/- 0.2 in A1AR(+/+) and A1AR(-/-)
      mice; early proximal flow rate response, -3.4 +/- 0.4 nl/min and +0.02 +/- 0.3
      nl/min in A1AR(+/+) and A1AR(-/-) mice). Absence of TGF responses in A1AR
      deficient mice suggests that adenosine is a required constituent of the
      juxtaglomerular signaling pathway. A1AR null mutant mice are a promising tool to
      study the functional role of A1AR in different target tissues.

PMID- 11504954
TI  - Effectiveness of syringe exchange programs in reducing HIV risk behavior and HIV
      seroconversion among injecting drug users.

PMID- 11504953
TI  - A cranium for the earliest Europeans: phylogenetic position of the hominid from
      Ceprano, Italy.
AB  - The human fossil evidence unequivocally pertaining to the first inhabitants of
      Europe at present includes the sample from Atapuerca-TD6 (Spain) and the
      incomplete adult calvaria discovered near Ceprano, in Southern Latium (Italy). On
      the basis of regional correlations and a series of absolute dates, the age of the
      Ceprano hominid is estimated to range between 800 and 900 kilo-annum (ka). In
      addition, the association with archaic (Mode 1) Paleolithic findings from the
      same area is suggested. After the completed reconstruction of the calvaria, we
      present here a new study dealing with the general and more detailed aspects of
      the morphology displayed by Ceprano, in comparison to fossil samples ranging
      between Early and Middle Pleistocene. According to our results, cranial features
      indicate that Ceprano represents a unique morphological bridge between the clade
      Homo ergaster/erectus and later Middle Pleistocene specimens commonly referred to
      Homo heidelbergensis (and/or to Homo rhodesiensis), particularly those belonging
      to the African fossil record that ultimately relates to the origin of modern
      humans. In conclusion, given its geographical, chronological, and phylogenetic
      position, an attribution to the species Homo antecessor is considered, although
      the sample from Atapuerca-TD6 is not directly comparable to Ceprano.
      Alternatively, a new species-ancestral to later European and African hominines
      should be named to accommodate such a unique fossil specimen.

PMID- 11504955
TI  - Protective effect of CCR5 delta 32 heterozygosity is restricted by SDF-1 genotype
      in children with HIV-1 infection.
AB  - OBJECTIVE: To determine the influences on pediatric AIDS of a heterozygous 32
      base pair deletion in the CC-chemokine receptor 5 gene (CCR5 wt/Delta 32) and a
      common polymorphism in the 3' untranslated region of stromal cell-derived factor
      1 beta gene transcript (SDF1-3'A). DESIGN: The rate of HIV-1 disease progression
      and viral burden were compared according to the CCR5 and SDF-1 genotypes in 127
      (58 Caucasians, 60 African-Americans and nine Hispanics) perinatally HIV-1
      infected children. RESULTS: Regardless of ethnic background, the CCR5 wt/Delta 32
      genotype was associated with a delayed onset of AIDS-defining infectious
      complications during the first 5 years of infection [relative hazard (RH) = 0.22;
      95% confidence interval (CI), 0.012--1.02; P = 0.053]. Similarly, CCR5 wt/Delta
      32 conferred an early protection against severe immune suppression and HIV-1
      encephalopathy, but only in those without SDF1-3'A (RH = 0; 95% CI, 0--0.70; P =
      0.020, and RH = 0; 95% CI, 0--0.71; P = 0.021, respectively). When examined
      before 5 years of age (n = 81), the children with CCR5 wt/Delta 32 had
      significantly lower levels of cell-associated HIV-1 DNA than wild-type
      homozygotes (P = 0.016, adjusted by race), while SDF1-3'A carriers had relatively
      higher levels (P = 0.047, adjusted by race). Although the disease-retarding
      effect of CCR5 wt/Delta 32 subsequently disappeared, time to death was still
      significantly delayed in the CCR5 Delta 32 heterozygotes without SDF1-3'A (RH =
      0; 95% CI, 0--0.53; P = 0.008). CONCLUSION: In pediatric AIDS, the protective
      effect of CCR5 wt/Delta 32 is more pronounced in early years of infection and
      appears to be abrogated by the SDF1-3'A genotype.

PMID- 11504956
TI  - P-Glycoprotein and transporter MRP1 reduce HIV protease inhibitor uptake in CD4
      cells: potential for accelerated viral drug resistance?
AB  - BACKGROUND: The multidrug transporters P-glycoprotein (P-gp) and MRP1 are
      functionally expressed in several subclasses of lymphocytes. HIV-1 protease
      inhibitors interact with both; consequently the transporters could reduce the
      local concentration of HIV-1 protease inhibitors and, thus, influence the
      selection of viral mutants. OBJECTIVES: To study the effect of the expression of
      P-gp and MRP1 on the transport and accumulation of HIV-1 protease inhibitors in
      human lymphocytes and to study the effects of specific P-gp and MRP1 inhibitors.
      METHODS: The initial rate and the steady-state intracellular accumulation of
      radiolabelled ritonavir, indinavir, saquinavir and nelfinavir was measured in
      three human lymphocyte cell lines: control CEM cells, CEM-MDR cells, which
      express 30-fold more P-gp than CEM cells, and CEM-MRP cells, which express
      fivefold more MRP1 protein than CEM cells. The effect of specific inhibitors of P
      gp (GF 120918) and MRP1 (MK 571) was also examined. RESULTS: Compared with CEM
      cells, the initial rates of uptake and the steady-state intracellular
      concentrations of all protease inhibitors are significantly reduced in CEM-MDR
      cells. The intracellular concentrations of the protease inhibitors are increased
      upon co-administration with GF 120918, in some cases to levels approaching those
      in CEM cells. The intracellular concentrations of the protease inhibitors are
      also significantly reduced in CEM-MRP cells. Co-administration with MK -571 can
      partially overcome these effects. CONCLUSIONS: The overexpression of multidrug
      transporters significantly reduces the accumulation of protease inhibitors at
      this major site of virus replication, which, potentially, could accelerate the
      acquisition of viral resistance. Targeted inhibition of P-gp may represent an
      important strategy by which this problem can be overcome.

PMID- 11504957
TI  - Kinetics of HIV-1 RNA and resistance-associated mutations after cessation of
      antiretroviral combination therapy.
AB  - OBJECTIVE: To study the kinetics of HIV-1 RNA and drug-induced mutations after
      cessation of antiretroviral therapy (ART). DESIGN AND METHODS: Successive plasma
      samples from 26 patients were tested for HIV-1 RNA by PCR and for mutations
      associated with drug resistance by sequencing of the pol gene. RESULTS: After
      cessation of ART the phase of undetectable virus (< 50 copies/ml), ranging from 6
      to more than 29 days, was followed by a rapid viral increase, which slowed down
      before a plateau corresponding to pre-treatment levels or higher was reached in
      most cases (14/19 patients). In one patient virus was still undetectable at 4
      weeks. Also, a significantly larger number of primary protease inhibitor (PI)
      associated mutations reverted to wild-type, as compared with secondary PI-, and
      primary reverse transcriptase inhibitor (RTI)-associated mutations. During the
      rapid viral increase no mutations disappeared, which instead happened during the
      slower viral increase preceding the viral plateau level. CONCLUSION: After
      discontinuation of ART large individual variations were found for the time period
      until HIV-1 became detectable in plasma, possibly due to differences in the HIV-1
      specific immunity. The more rapid loss of primary PI mutations suggests that they
      might cause a more impaired viral fitness than primary RTI mutations. However,
      the persistence of drug mutations during the initial viral load increase
      indicates that mutated strains may still replicate efficiently.

PMID- 11504958
TI  - Overview of the effectiveness of triple combination therapy in antiretroviral
      naive HIV-1 infected adults.
AB  - AIM: To estimate the effectiveness of triple combination therapy in
      antiretroviral-naive adults. METHODS: A systematic overview of results from
      clinical trials involving triple combination therapy with dual nucleoside reverse
      transcriptase inhibitors (NRTI) and: a protease inhibitor (PI triple); a non
      nucleoside reverse transcriptase inhibitor (NNRTI triple); or a third NRTI
      (triple NUC). Data from 23 clinical trials involving 31 independent treatment
      groups, 19 unique antiretroviral regimens, and 3257 enrolled patients were
      included in this study. RESULTS: Median log(10) baseline plasma HIV RNA and CD4
      cell count over all trials averaged 4.69 (49,329 copies/ml) and 375 x 10(6)
      cells/l, respectively. The overall estimated percentage of patients with plasma
      HIV RNA < or = 400 copies/ml at 24 weeks was 64% [95% confidence interval (CI),
      60 to 67%]. The percentages of patients with plasma HIV RNA < or = 50 copies/ml
      at 48 weeks by drug class were: PI triple, 46% (95% CI, 41 to 52%); NNRTI triple,
      51% (95% CI, 43 to 59%); triple NUC, 45% (95% CI, 36 to 54%). The CD4 cell count
      increase over all trials at 24 and 48 weeks averaged +123 x 10(6) cells/l (95%
      CI, 111 x 10(6) to 135 x 10(6) cells/l) and +160 x 10(6) cells/l (95% CI, 146 x
      10(6) to 175 x 10(6) cells/l), respectively and did not differ between drug
      classes. In multivariable regression analysis, neither baseline plasma HIV RNA
      level and CD4 cell count nor treatment regimen predicted plasma HIV RNA < or = 50
      copies/ml at week 48. However, pill count was significantly negatively associated
      with plasma HIV RNA < or = 50 copies/ml at week 48 (P = 0.0085). CONCLUSIONS: The
      results suggest that three drug regimens containing two NRTI with a PI, a NNRTI,
      or a third NRTI may provide comparable activity, and practical issues such as
      daily pill burden should be considered when choosing a treatment regimen.

PMID- 11504959
TI  - Effects of treatment intensification with hydroxyurea in HIV-infected patients
      with virologic suppression.
AB  - BACKGROUND: Virologic rebound can result from suboptimal antiviral potency in
      combination antiretroviral therapy. DESIGN: Multicenter, partially blinded,
      prospective, randomized study of 202 HIV-infected subjects to determine whether
      therapy intensification improves long-term rates of virologic suppression.
      METHODS: Subjects had plasma HIV RNA < 200 copies/ml, CD4 cell count of > 200 x
      10(6) cells/l, and treatment with indinavir (IDV) + zidovudine (ZDV) + lamivudine
      (3TC) for at least 6 months before randomization to stay on this regimen or to
      receive IDV + didanosine (ddI) + stavudine (d4T) plus or minus hydroxyurea (HU)
      (600 mg twice daily). Treatment failure was defined as either confirmed rebound
      of HIV RNA level to > 200 copies/ml or a drug toxicity necessitating treatment
      discontinuation. RESULTS: Treatment failure occurred more frequently in subjects
      randomized to the HU-containing arm (32.4%), than in those taking IDV + ddI + d4T
      (17.6%) or IDV + ZDV + 3TC (7.6%). The time to treatment failure was shorter for
      the HU-containing arm compared with the IDV + ZDV + 3TC (P < 0.0001) or IDV + ddI
      + d4T arms (P = 0.032). Dose-limiting toxicities rather than virologic rebound
      accounted for the differences between treatment failure among the study arms.
      Pancreatitis led to treatment discontinuation in 4% of subjects in treatment arms
      containing ddI + d4T. Three subjects with pancreatitis died, all randomized to
      the HU-containing arm. CONCLUSIONS: Switching to IDV + ddI + d4T + HU in patients
      treated with IDV + ZDV + 3TC was associated with a worse outcome, principally
      because of drug toxicity.

PMID- 11504960
TI  - Clinical assessment of HIV-associated lipodystrophy in an ambulatory population.
AB  - OBJECTIVE: To identify clinical factors associated with prevalence of fat atrophy
      (lipoatrophy) and fat accumulation (lipoaccumulation) in HIV-1 infected patients.
      DESIGN: Evaluation of HIV-1 infected patients seen for routine care between 1
      October and 31 December 1998 in the eight HIV Outpatient Study (HOPS) clinics.
      SETTING: Eight clinics specializing in the care of HIV-1 infected patients.
      PATIENTS: A total of 1077 patients were evaluated for signs of fat
      maldistribution. INTERVENTIONS: A standardized set of questions and specific
      clinical signs were assessed. Demographic, clinical and pharmacological data for
      each patient were also included in the analysis. MAIN OUTCOME MEASURES:
      Demographic, immunologic, virologic, clinical, laboratory, and drug treatment
      factors were assessed in stratified and multivariate analyses for their
      relationship to the presence and severity of fat accumulation and atrophy.
      RESULTS: Independent factors for moderate/severe lipoatrophy for 171 patients
      were increasing age, any use of stavudine, use of indinavir for longer than 2
      years, body mass index (BMI) loss, and measures of duration and severity of HIV
      disease. Independent risk factors for moderate/severe fat accumulation for 104
      patients were increasing age, BMI gain, measures of amount and duration of immune
      recovery, and duration of antiretroviral therapy (ART). The number of non-drug
      risk factors substantially increased the likelihood of lipoatrophy. If non-drug
      risk factors were absent, lipoatrophy was unusual regardless of the duration of
      drug use. CONCLUSIONS: HIV-associated lipodystrophy is associated with several
      host, disease, and drug factors. While prevalence of lipoatrophy increased with
      the use of stavudine and indinavir, and lipoaccumulation was associated with
      duration of ART, other non-drug factors were strongly associated with both fat
      atrophy and accumulation.

PMID- 11504961
TI  - Educational level is associated with condom use within non-spousal partnerships
      in four cities of sub-Saharan Africa.
AB  - BACKGROUND: Rates of condom use in sub-Saharan Africa have remained too low to
      curb HIV/sexually transmitted disease (STD) epidemics. A better understanding of
      the main determinants of condom use would aid promotion. METHODS: Cross-sectional
      population surveys were conducted in four cities in sub-Saharan Africa: Yaounde,
      Cameroon; Cotonou, Benin; Ndola, Zambia; and Kisumu, Kenya. In each city, the aim
      was to interview a random sample of 1000 men and 1000 women aged 15--49 years,
      including questions on characteristics of non-spousal partnerships in the past 12
      months. RESULTS: Data on condom use were available for 4624 non-spousal
      partnerships. In the four cities, the proportion of partnerships in which condoms
      were used always or most of the time ranged from 23.8 to 33.5% when reported by
      men and from 10.7 to 25.9% when reported by women. Based on the reports from men,
      condom use was associated with higher educational level of the male partner in
      Yaounde [adjusted odds ratio (aOR) = 1.76] and Ndola (aOR = 2.94) and with higher
      educational level of the female partner in Cotonou (aOR = 2.36) and Kisumu (aOR =
      2.76). Based on the reports from women, condom use was associated with higher
      educational level of the female partner in Kisumu (aOR = 2.60) and Ndola (aOR =
      4.50) and with higher educational level of the male partner in Yaounde (aOR =
      3.32). Associations with other determinants varied across cities and for men and
      women. CONCLUSIONS: Education was found to be a key determinant of condom use in
      all four cities. This suggests that educational level increases response to
      condom promotion and highlights the need for special efforts to reach men and
      women with low educational attainment.

PMID- 11504962
TI  - Seeking sex on the Internet and sexual risk behaviour among gay men using London
      gyms.
AB  - OBJECTIVE: To examine the association between seeking sex on the Internet and
      sexual risk behaviour among gay men in London. METHODS: In January-February 2000,
      gay men in London gyms were asked to complete self-administered questionnaires
      concerning use of the Internet, history of sexually transmitted diseases (STD)
      and recent unprotected anal intercourse (UAI). Internet sex seekers were compared
      with other men, also with Internet access, who did not seek sex in this way.
      RESULTS: Of 743 gay men included in the analysis (121 HIV-positive, 465 HIV
      negative, 157 never-tested), 80.9% (601) had access to the Internet. Among those
      who had access, 34.4% (207) had used the Internet to find a sexual partner; this
      did not vary significantly by HIV status (P = 0.3). Internet sex seekers were
      more likely to have had an STD (HIV-negative men, 26.9 versus 17.5%, P = 0.04) or
      gonorrhoea (HIV-positive men, 22.2 versus 5.8%, P = 0.04) in the previous year
      than other men with Internet access. HIV-negative Internet sex seekers were also
      more likely to report non-concordant UAI in the previous 3 months [23.1 versus
      11.8%; adjusted odds ratio (aOR), 1.9; 95% confidence interval (CI), 1.2--3.5; P
      = 0.01]. HIV-positive Internet sex seekers were more likely to report UAI with
      another positive man (37.8 versus 7.4%; aOR, 7.9; 95% CI, 1.8--34.6; P = 0.006).
      CONCLUSION: Seeking sex on the Internet was associated with recent STD and high
      risk sexual behaviour among HIV-positive and -negative gay men in London. The
      contribution of seeking sex on the Internet to the recent increase in high-risk
      behaviour among London gay men merits further investigation.

PMID- 11504963
TI  - Tampons as a self-administered collection method for the detection and
      quantification of genital HIV-1.
AB  - OBJECTIVE: To assess the detection and quantitation of HIV-1 from tampon eluents
      in comparison with cervicovaginal lavage (CVL) and plasma specimens from the same
      women. METHODS: Ninety-seven tampon, 105 CVL, and 104 plasma specimens from 105
      HIV-1 seropositive women were analyzed using Version 3 of the Chiron bDNA assay,
      with sensitivity of 50 HIV-1 RNA copies/ml. Data analyses used McNemar's test,
      Wilcoxon signed rank test, and Mantel--Haenszel chi-squared and odds ratios with
      95% confidence intervals to assess differences in proportions. RESULTS: In women
      for whom both plasma and genital specimens were available, HIV-1 was detected
      less frequently in genital specimens: [tampons (33/97, 34%) and CVL (48/104,
      46%)] than plasma specimens (86/104, 83%) (P < 0.001 for both plasma versus
      tampon and for plasma versus CVL). However, the proportion of genital specimens
      with detectable virus did not differ significantly by collection method (P =
      0.14). Among women with detectable virus using both collection methods (n = 23),
      viral load was similar for tampon eluents (median, 355 copies/ml; range, 52-
      120,898) and CVL specimens (median, 265 copies/ml; range, 61--35,637;P = 0.88).
      CONCLUSION: Tampon eluent specimens are slightly less sensitive than CVL
      specimens in the detection of genital HIV-1, although quantification of viral
      load, when detectable by both methods, was similar.

PMID- 11504964
TI  - Effect of interventions to control sexually transmitted disease on the incidence
      of HIV infection in female sex workers.
AB  - OBJECTIVE: To compare the seroincidence of HIV infection among female sex workers
      in Abidjan, Cote d'Ivoire before and during an intervention study to control
      sexually transmitted diseases (STD) and to study the effect of two STD diagnosis
      and treatment strategies on the prevalence of STD and on the seroincidence of HIV
      infection. METHOD: A screening facility for STD and HIV had been available since
      October 1992 for female sex workers. From June 1994, women who were HIV
      seronegative or HIV-2 positive during the screening could enroll in the
      intervention study in which participants reported once a month to a confidential
      clinic where they received health education, condoms and STD treatment if
      indicated. Women in the study were randomized either to a basic STD diagnosis and
      treatment strategy, which included a gynecologic examination when symptomatic, or
      to an intensive strategy that included a gynecologic examination regardless of
      symptoms. An outcome assessment every 6 months included a gynecologic
      examination, HIV serology and laboratory tests for STD. RESULTS: Of 542 women
      enrolled in the study, 225 (42%) had at least one outcome assessment. The HIV-1
      seroincidence rate during the intervention study was significantly lower than
      before the study (6.5 versus 16.3 per 100 person-years; P = 0.02). During the
      study, the HIV-1 seroincidence rate was slightly lower in the intensive than in
      the basic strategy (5.3 versus 7.6 per 100 person-years; P = 0.5). CONCLUSION:
      National AIDS control programs should consider adopting as policy the type of
      integrated approach used in this intervention study for HIV prevention in female
      sex workers.

PMID- 11504965
TI  - Sex and the internet.

PMID- 11504967
TI  - Cessation of secondary prophylaxis in patients with cryptococcosis.
AB  - Cryptococcal disease in HIV-positive individuals is usually a consequence of
      advanced immunosuppression. Treatment consists of long period of induction
      therapy followed by long-term secondary prophylaxis, usually with fluconazole.
      The introduction of highly active antiretroviral therapy has resulted in
      improvements in immunological function such that the cessation of primary and
      secondary prophylaxis against several opportunistic infections has become
      possible. We report our experience of the cessation of secondary antifungal
      prophylaxis in patients responding to highly active antiretroviral therapy.

PMID- 11504966
TI  - Early control of HIV replication in primary HIV-1 infection treated with
      antiretroviral drugs and pegylated IFN alpha: results from the Primoferon A (ANRS
      086) Study.
AB  - IFN alpha has both antiviral and immunostimulating properties. The ANRS086
      Primoferon A Study evaluated in 12 patients with primary HIV infection the
      tolerance and efficacy of an early and transient administration of pegylated IFN
      alpha, in addition to highly active antiretroviral therapy. Tolerance was good,
      and this regimen allowed the early control of HIV replication and rapid decay of
      the viral reservoir. These results support the initiation of comparative studies
      with pegylated INF alpha in primary HIV infection.

PMID- 11504968
TI  - Plasma HIV burden in Malawian children co-infected with rotavirus.
AB  - Fifty-eight HIV-infected children with acute rotavirus diarrhea were tested for
      plasma HIV RNA. There was no difference between acute and convalescent mean viral
      loads, and little change in CD4 cell counts. Compared with the 16 children who
      died within 4 weeks, 31 survivors had slightly lower viral loads at presentation
      and significantly higher CD4 cell counts. Low CD4 cell counts, but not HIV-1-RNA
      concentrations, were predictive of Death. Local, enteric rotavirus infection did
      not appear to affect blood HIV viral load or CD4 cell counts in this small group
      of children.

PMID- 11504969
TI  - HIV transmission risk among sub-Saharan Africans in London travelling to their
      countries of origin.
AB  - Migrant black African communities bear the brunt of heterosexual HIV/AIDS
      epidemic in the UK. This study confirms the close links that exist between UK
      resident black Africans and their countries of origin. A total of 43% of men and
      46% of women visited their home countries within the last five years. While
      there, men were more likely than women to have acquired a new sexual partner.
      Previous diagnosis with a sexually transmitted disease, and the use of condoms at
      last intercourse were independently associated with this practice. This
      represents a potential risk of HIV transmission, and highlights an area for
      targeted health promotion within these communities.

PMID- 11504970
TI  - Gynecomastia without lipodystrophy syndrome in HIV-infected men treated with
      efavirenz.

PMID- 11504971
TI  - Discontinuation of secondary prophylaxis against cryptococcosis in patients with
      AIDS receiving highly active antiretroviral therapy.

PMID- 11504972
TI  - Multiple mitochondrial DNA deletions and lactic acidosis in an HIV-infected
      patient under antiretroviral therapy.

PMID- 11504973
TI  - An argument for mitochondrial toxicity in highly active antiretroviral therapy
      induced lipoatrophy.

PMID- 11504975
TI  - New SIV strains found among monkeys and chimps in Africa.

PMID- 11504977
TI  - High proportion of unrelated HIV-1 intersubtype recombinants in the Mbeya region
      of southwest Tanzania.
AB  - BACKGROUND: In Mbeya, a rural region of southwest Tanzania, HIV-1 subtypes A, C
      and D have been co-circulating since the early 1990s. OBJECTIVE: To define to
      what extent the co-existence of subtypes has led to recombinant HIV-1 strains and
      whether there is evidence for epidemic spread of any circulating recombinant
      form. METHODS: Nine HIV-1-seropositive young adults from Mbeya Town with no
      evident high-risk behaviour contributed peripheral blood mononuclear cells for
      this study. Nine virtually full-length-genome-sequences were amplified from this
      DNA and phylogenetically analysed. RESULTS: Out of the nine samples, two were
      subtype A (22%), two were subtype C (22%) and five were recombinants (56%): four
      A/C recombinants and one C/D recombinant. None of the recombinants were related
      to each other; all of them had different mosaic structures. Most of the genome in
      the recombinants was subtype C. CONCLUSION: A high proportion of unrelated
      intersubtype recombinants, none of them apparently spreading in the population,
      may be present in southwest Tanzania.

PMID- 11504976
TI  - Genotypic variation of HIV-1 reverse transcriptase and protease: comparative
      analysis of clade C and clade B.
AB  - OBJECTIVE: To compare drug-resistant variants from untreated (naive) and treated
      patients infected with clade B or C virus. METHODS: Consecutive samples (165)
      from patients throughout Israel were analyzed. All those in the treated group
      were failing highly active antiretroviral therapy. RESULTS: There were 87 clade B
      (14 naive) and 78 clade C (20 naive) [corrected] with significant differences in
      the prevalence of known drug-resistance mutations between the clades: in naive
      patients in the protease region M36I 7% and 95% (P < 0.0001), K20R 0% and 27% (P
      = 0.063), A71V 18% and 0% (P = 0.063), M46I 0% and 13%, and V77I 18% and 0% (P =
      0.063), respectively, and in the reverse transcriptase region A98G/S 0% and 20%
      (P = 0.12), respectively. Most clade C viruses also showed significant
      differences from clade B consensus sequence at additional protease sites: R41K
      100%, H69K/Q 85%, L89M 95% and I93L 80% (P < 0.0001). There were also significant
      differences (P < 0.03 to < 0.0001) in treated patients in clades B and C: in the
      protease region L10I 40% and 12%, M36I 26% and 95%, L63P 67% and 40%, A71I 38%
      and 7%, G73I and V77I 18% and 0%, I84V 16% and 3%, and L90M 40% and 12%,
      respectively; in the reverse transcriptase M41L 41% and 17%, D67N 41% and12%,
      K70R 30% and 7%, T215Y 48% and 29%, K219Q 21% and 7%, and A98G/S 3% and 24%,
      respectively. CONCLUSION: Significantly differences between clade B and C viruses
      may be associated with development of differing resistance patterns during
      therapy and may affect drug utility in patients infected with clade C.

PMID- 11504978
TI  - Comparison of genotyping and phenotyping methods for determining susceptibility
      of HIV-1 to antiretroviral drugs.
AB  - OBJECTIVE(S): To compare antiretroviral resistance susceptibility testing of
      patient HIV-1 strains using genotype and phenotype methods. DESIGN: Eighteen
      plasma samples with viral load > 2000 HIV-1 RNA copies/ml were randomly selected
      for testing by both methods. Disease and treatment data were available for all
      patients. METHODS: Samples were analysed genotypically using a kit assay (HIV-1
      Genotyping Systems, Applied Biosystems), performed by the Clinical Research
      Laboratory at Macfarlane Burnet Centre for Medical Research. Samples were
      analysed phenotypically using a rapid phenotypic assay (PhenoSenseTM HIV,
      ViroLogic), performed by the manufacturer. Results from both methods were
      interpreted using a defined protocol. Each susceptibility assay was performed and
      interpreted by individuals unaware of either the clinical data or the results of
      the other susceptibility assay. Concordance was defined categorically as either
      the presence of reduced susceptibility (> 2.5-fold change) in the phenotypic
      assay and resistance associated mutations in the genotypic assay, or the absence
      of these findings in both assays. RESULTS: Concordance between phenotypic and
      genotypic susceptibility testing was 81% for nucleoside reverse transcriptase
      inhibitors, 91% for non-nucleoside reverse transcriptase inhibitors and 90% for
      protease inhibitors. Complete concordance between phenotype and genotype for all
      14 drugs evaluated was observed in three (17%) patient samples. CONCLUSIONS:
      Phenotypic and genotypic susceptibility appear to provide similar results.
      However, interpretation of genotypic results can be complicated, and both methods
      still require clinical validation.

PMID- 11504979
TI  - Lymphoid tissue viral burden and duration of viral suppression in plasma.
AB  - OBJECTIVES: To assess virological response in lymphoid tissue and its impact on
      the durability of response in plasma in HIV-1-infected persons who achieved
      sustained suppression of plasma viraemia with different antiretroviral regimens.
      METHODS: Consecutive patients on first-line antiretroviral therapy were included
      if they had a plasma HIV-1 RNA viraemia < 20 copies/ml within the last 6 months
      and tonsillar tissue accessible for biopsy. First-line therapy contained two
      nucleoside analogues: alone (2NRTI group, n = 3); plus a HIV-1 protease inhibitor
      (PI group, n = 11) or plus nevirapine (NVP group; n = 16). Patients were followed
      until virus was detectable in plasma, they changed therapy or were lost to follow
      up. RESULTS: Tonsillar HIV-1 RNA could be detected (> 100 copies/mg) in 10
      patients: one in the PI group (9%), six (38%) in the NVP group and in all three
      patients in the 2NRTI group. Primary resistance mutations could be detected in
      only 2 of these 10 patients. After a median of 9 months after the biopsies, viral
      suppression in plasma had failed in 6 of these 10 patients whereas failure had
      only occurred in 1 out of 20 with initially undetectable viral load in lymphoid
      tissue (P = 0.01; log rank test). CONCLUSIONS: In patients with sustained viral
      suppression in plasma, triple therapy including a HIV-1 protease inhibitor was
      more potent than triple therapy containing nevirapine or dual therapy with
      nucleoside analogues to reduce viral burden in lymphoid tissue. A worse response
      in lymphoid tissue could not be explained by local selection of resistance and
      was associated with a less durable virological response in plasma.

PMID- 11504980
TI  - Better response to chemotherapy and prolonged survival in AIDS-related lymphomas
      responding to highly active antiretroviral therapy.
AB  - OBJECTIVES: To evaluate the impact of response to highly active antiretroviral
      therapy (HAART) on the natural history of AIDS non-Hodgkin's lymphoma (NHL) and
      to analyse the feasibility, efficacy and toxicity of HAART in combination with
      chemotherapy. DESIGN: Prospective observational study in two AIDS clinical
      centres in Italy. METHODS: All consecutive HIV-infected patients with NHL were
      included (n = 44; 48% high-risk group) and prospectively followed for 27 months.
      HAART was administered concomitantly with chemotherapy. The association between
      response to HAART and clinical presentation, response to chemotherapy and
      toxicity was analysed by univariate and multivariate models. Survival analysis
      was performed by Kaplan-Meier estimates and the Cox proportional hazards
      regression model. RESULTS: A complete response (CR) to chemotherapy was achieved
      in 71% of HAART responders and 30% of non-responders. Virological response to
      HAART was the only variable associated with tumour response on multivariate
      analysis. A higher relative dose intensity (RDI) of chemotherapy was administered
      in patients with virological response compared with those without. The
      probability of 1 year survival was higher in patients with virological or
      immunological response. At Cox regression analysis, immunological response, a
      higher RDI and a CR to chemotherapy were all associated with a reduced risk of
      death. CONCLUSION: In HIV-infected patients with NHL, response to HAART was
      strongly associated with a better response to chemotherapy and prolonged
      survival. Concurrent treatments were well tolerated, and HAART-responder patients
      could receive a higher RDI of chemotherapy. In patients with AIDS lymphomas,
      combining HAART with chemotherapy could be a feasible and effective approach.

PMID- 11504981
TI  - Impact of baseline polymorphisms in RT and protease on outcome of highly active
      antiretroviral therapy in HIV-1-infected African patients.
AB  - OBJECTIVE: To assess the therapeutic response and investigate the significance of
      polymorphic codons in African patients receiving highly-active antiretroviral
      therapy (HAART). DESIGN AND METHODS: African patients were identified from the St
      Mary's Hospital HIV-1 database. Clinical outcome was assessed by viral load and
      CD4 cell count. Pre- and post-therapy sequences of RT and protease were analysed.
      The impact of subtype and individual polymorphic codons on therapeutic outcome
      was assessed statistically (Fishers exact and chi2 tests) and phylogenetically
      (Jukes and Cantor). RESULTS: Of 79 drug-naive African patients who were
      prescribed HAART, 60 remained undetectable for 1 year, with no differences
      detected in the clinical response to non-nucleoside reverse transcriptase
      inhibitor (NNRTI)- or protease inhibitor (PI)-containing regimes. Country of
      origin, sex and viral subtype had no impact on outcome of HAART. A total of 133
      polymorphisms were identified in pol (37 in protease and 96 in RT), with a mean
      of 9.0 in protease and 22.3 in RT per patient. There was no significant
      difference in the overall numbers of polymorphisms per patient, and no single
      polymorphism had any impact on clinical outcome. Sequences from 'failing'
      patients experiencing viral rebound produced few mutations known to be associated
      with drug resistance, suggesting minimal drug pressure. CONCLUSIONS: The response
      of patients infected with African subtypes of HIV-1 to HAART appears to be
      independent of regime, HIV-1 clade and baseline polymorphisms. Non-B subtypes are
      fully sensitive to HAART and, accordingly, therapy should not be withheld from
      African patients for reasons of viral diversity.

PMID- 11504982
TI  - Dietary advice with or without pravastatin for the management of
      hypercholesterolaemia associated with protease inhibitor therapy.
AB  - BACKGROUND: Therapy with a HIV protease inhibitor is associated with elevations
      in cholesterol and triglycerides. HMG-CoA reductase inhibitors ('statins') are
      the established therapy for persons with primary hypercholesterolaemia. Because
      of drug interactions, pravastatin may represent the preferred choice in those
      taking HIV protease inhibitors. DESIGN: A randomized, open-label comparative 24
      week trial of dietary advice alone or with pravastatin in 31 male patients
      established on protease inhibitor-based regimens for greater than 12 weeks with
      viral load < 500 copies/ml and cholesterol > 6.5 mmol/l. RESULTS: There were no
      significant clinical or laboratory events and no patient discontinuation
      secondary to adverse effects. Viral rebound did not occur. Relative to baseline,
      total cholesterol at week 24 fell significantly in the pravastatin (1.2 mmol/l;
      17.3%) (P < 0.05) but not in the dietary advice (0.3 mmol/l; 4%) group. The
      difference between the two groups approached significance at week 24 (P = 0.051).
      This fall was accounted for entirely by a reduction in low density lipoprotein
      [calculated change 1.24 mmol/l (19%) and 0.07 mmol (5.5%) in pravastatin and
      dietary advice groups, respectively] as high density lipoprotein rose non
      significantly by 0.6 mmol/l in both groups. Weight, basal metabolic rate, fasting
      glucose and triglycerides did not change significantly in either group.
      CONCLUSIONS: Dietary advice plus pravastatin significantly reduced total
      cholesterol in HIV-positive individuals taking protease inhibitors, without
      significant adverse effects. The inclusion of pravastatin substantially increases
      the magnitude of the change, which is comparable with changes achieved in
      endogenous hyperlipidaemia.

PMID- 11504983
TI  - A prospective study of discontinuing primary and secondary Pneumocystis carinii
      pneumonia prophylaxis after CD4 cell count increase to > 200 x 106 /l.
AB  - OBJECTIVE: To assess the incidence of Pneumocystis carinii pneumonia (PCP) after
      discontinuation of either primary or secondary prophylaxis. DESIGN: This was a
      prospective, non-randomized, non-blinded study. SETTING: Twenty-five University
      based AIDS Clinical Trials Group units. PARTICIPANTS: Participants either had a
      CD4 cell count < or = 100 x 106/l at any time in the past and no history of
      confirmed PCP (group I; n = 144), or had a confirmed episode of PCP > or = 6
      months prior to study entry (group II; n = 129). All subjects had sustained CD4
      cell counts > 200 x 106/l in response to antiretroviral therapy. INTERVENTIONS:
      Subjects discontinued PCP prophylaxis within 3 months or at the time of study
      entry. Evaluations for symptoms of PCP and CD4 cell counts were performed every 8
      weeks. Prophylaxis was resumed if two consecutive CD4 cell counts were < 200 x
      106/l. MAIN OUTCOME MEASURE(S): The main outcome was development of PCP. RESULTS:
      No cases of PCP occurred in 144 subjects (median follow-up, 82 weeks) in group I
      or in the 129 subjects (median follow-up, 63 weeks) in group II (95% upper
      confidence limits on the rates of 1.3 per 100 person-years and 1.96 per 100
      person-years for groups I and II, respectively). Eight subjects (five in group I
      and three in group II) resumed PCP prophylaxis after two consecutive CD4 cell
      counts < 200 x 106/l. CONCLUSIONS: The risk of developing initial or recurrent
      PCP after discontinuing prophylaxis is low in HIV-infected individuals who have
      sustained CD4 cell count increases in response to antiretroviral therapy. Neither
      lifelong primary nor secondary PCP prophylaxis is necessary.

PMID- 11504984
TI  - Simplification with abacavir-based triple nucleoside therapy versus continued
      protease inhibitor-based highly active antiretroviral therapy in HIV-1-infected
      patients with undetectable plasma HIV-1 RNA.
AB  - OBJECTIVE: To assess the antiviral efficacy, safety and adherence in patients
      switched to an abacavir-containing nucleoside reverse transcriptase inhibitor
      (NRTI) regimen after long-term HIV-1 RNA suppression with a dual NRTI/protease
      inhibitor (PI) combination. METHODS: In an open-label, multicentre study,
      patients receiving 2NRTI plus PI for at least 6 months, with a history of
      undetectable plasma HIV-1 RNA since the initiation of therapy and plasma HIV-1
      RNA < 50 copies/ml at screening, were randomly assigned to replace the PI with
      abacavir (n = 105) or continue the same treatment (n = 106). Clinical assessments
      included plasma HIV-1 RNA, chemistry, haematology, lymphocyte counts, and adverse
      event reports. Adherence to treatment was assessed by patient self-report.
      RESULTS: A significantly longer time to treatment failure was demonstrated in the
      abacavir arm compared with the PI arm (P = 0.03) while treatment failure was
      experienced by significantly more patients in the PI arm: 24 (23%) versus 12
      (12%) (P = 0.03). Therapy-limiting toxicity led to treatment failure in eight
      versus 14 cases in the abacavir and PI arms, respectively, whereas virological
      rebound was the cause in four versus two cases. Significant reductions in
      cholesterol and non-fasting triglyceride plasma levels at 48 weeks were observed
      in the abacavir arm (P < 0.001 andP = 0.035, respectively). The number of
      patients reporting no difficulty in taking their therapy showed a marked increase
      from baseline in the abacavir arm. CONCLUSION: The replacement of PI by abacavir
      in a triple combination regimen following prolonged suppression of plasma HIV-1
      RNA provides continued virological suppression, significant improvements in lipid
      abnormalities and enhanced ease of dosing.

PMID- 11504985
TI  - Puberty in perinatal HIV-1 infection: a multicentre longitudinal study of 212
      children.
AB  - OBJECTIVE: To define age at entry into Tanner stages in children with perinatal
      HIV-1 infection. DESIGN: Multicentre longitudinal study including 212 perinatally
      HIV-1-infected children (107 girls and 105 boys) followed-up during puberty (from
      8 and 9 years onwards in girls and boys, respectively). Healthy children (843
      girls and 821 boys) provided reference percentiles. P2 or B2 stages in girls and
      P2 or G2 stages in boys defined onset of puberty. METHODS: The cumulative
      probability [95% confidence limit (CI)] of entry into each stage at different
      ages was estimated by the Kaplan-Meier product-limit method; differences were
      evaluated by log rank test. Relationships were tested using the Spearman's rank
      correlation coefficient. RESULTS: Ages of girls [years (95%CI)] at P2 [12.9 (12.6
      13.2)], P3 [13.4 (13.0-13.8)], P4 [14.6 (14.0-15.2)], B2 [12.7 (12.2-13.2)], B3
      [13.3 (12.8-14.0)] and B4 [14.6 (14.0-15.2)] stages were > 97th percentile (> or
      = 21 month delay) of controls. Ages of boys [years (95%CI)] at P2 [12.6 (12.1
      13.1)], P3 [13.9 (13.4-14.4)], P4 [14.9 (14.2-15.6)], G2 [12.1 (11.5-12.7)], G3
      [13.6 (13.1-14.1)] and G4 [14.9 (14.1-15.7)] stages were at the 75-97th
      percentiles (< or = 15 month delay). Age at onset of puberty was not related to
      clinical and immunological condition, antiretroviral treatment, weigh for height
      and age at onset of severe disease or immune suppression. CONCLUSION: Perinatal
      HIV-1 infection interferes with sexual maturation. The mechanisms by which this
      occurs should be elucidated and intervention strategies designed. Intervention
      could save much psychological distress, since associated linear growth failure
      can exacerbate adolescents' feelings of being different and unwell.

PMID- 11504986
TI  - A menstrual cycle pattern for cytokine levels exists in HIV-positive women:
      implication for HIV vaginal and plasma shedding.
AB  - OBJECTIVES: To evaluate the effect of the menstrual cycle in HIV-positive women
      on plasma and genital cytokine levels, interrelationships between vaginal and
      plasma cytokines, CD4 and CD8 T cell fluctuations, and genital and plasma viral
      loads. METHODS: Plasma and cervicovaginal lavage specimens were collected from 55
      HIV-positive women with CD4 cell counts < 350 cells/microl during phases of the
      menstrual cycle. Samples were assayed for IL-1beta, IL-6, IL-4, IL-8, IL-10,
      TGFbeta, TNFalpha, INFgamma, MIP1alpha, MIP1beta, RANTES, and TNFR-II using
      enzyme-linked immunosorbent assays. CD4 and CD8 T cell expression was evaluated
      by flow cytometry. Repeated measures regression models were used to assess the
      effect of the menstrual cycle on cytokines and viral load. Multivariate repeated
      regression models were used to assess the correlation among selected cytokines
      and between selected cytokines and HIV viral load. RESULTS: Vaginal IL-1beta, IL
      4, IL-6, IL-8, IL-10, MIP1beta, RANTES, TGFbeta, and TNFR-II were significantly
      elevated during menses but were not altered during other phases. Plasma cytokine
      levels were not altered during the menstrual cycle. A positive Candida culture
      increased vaginal IL-8 during menses, whereas vaginal discharge was associated
      with a reduction in vaginal IL-4, IL-10, and RANTES. CD4 and CD8 cell numbers did
      not vary with the menstrual cycle. Vaginal cytokine levels correlated only with
      vaginal viral load, in a sampling method-dependent manner. CONCLUSION: We provide
      evidence of elevated vaginal cytokine levels during menses, which appear to
      regulate vaginal and not plasma HIV shedding, suggesting that a menstrual cycle
      pattern exists for cytokine production in HIV-positive women impacting vaginal
      shedding of HIV.

PMID- 11504987
TI  - Epidemiological analysis of the quality of HIV sero-surveillance in the world:
      how well do we track the epidemic?
AB  - OBJECTIVE: The objective of this paper was to analyse the quality of HIV/AIDS
      sentinel surveillance systems in countries and the resulting quality of the data
      used to make estimates of HIV/AIDS prevalence and mortality. METHODS: Available
      data on sero-surveillance of HIV/AIDS in countries were compiled in the process
      of making the end of 1999 estimates of HIV/AIDS. These data came primarily from
      the HIV/AIDS Surveillance Database developed by the United States Census Bureau,
      from a database maintained by the European Centre for the Epidemiological
      Monitoring of AIDS and all country reports on sentinel surveillance that had been
      provided to World Health Organization or UNAIDS. Procedures were developed to
      score quality of surveillance systems based on four dimensions of quality:
      timeliness and frequency; appropriateness of groups; consistency of sites over
      time; and coverage provided by the system. In total, the surveillance systems
      from 167 countries were analysed. RESULTS: Forty-seven of the 167 countries whose
      surveillance systems were rated were judged to have fully implemented sentinel
      surveillance systems; 51 were judged to have systems that had some or most
      aspects of a good HIV surveillance system in place and 69 were rated as having
      poorly functioning or non-existent surveillance systems. CONCLUSION: This
      analysis suggests that the quality of HIV surveillance varies considerably. The
      majority of countries most affected by HIV/AIDS have systems that are providing
      sufficient sero-prevalence data for tracking the epidemic and making reasonable
      estimates of HIV prevalence. However, many countries have poor systems and
      strengthening these is an urgent priority.

PMID- 11504988
TI  - Timing of the HIV-1 subtype C epidemic in Ethiopia based on early virus strains
      and subsequent virus diversification.
AB  - OBJECTIVE: To trace the introduction of HIV-1 subtype C into Ethiopia based on
      virus diversification during the epidemic. DESIGN: A set of 474 serum samples
      obtained in Ethiopia in 1982-1985 was tested for HIV-1. HIV-1 env gp120 V3 and
      gag or pol regions were sequenced and analysed together with sequences from later
      stages of the epidemic. RESULTS: None of 98 samples from 1982-1983, one of 193
      samples from 1984, and one of 183 samples from 1985 were HIV-1 positive.
      Phylogenetic analysis of virus sequences from positive samples revealed that they
      belong to the Ethiopian C, and not the C', cluster. Analysis of 81 Ethiopian C V3
      sequences from 1984-1997 revealed that the consensus sequence of the Ethiopian
      epidemic has been stable over time. Both the 1984 and 1985 V3 sequences, in
      contrast with three out of 27 (11%) of the 1988 and none out of 51 of the 1992
      1997 sequences, had no synonymous substitutions compared to the reconstructed
      common ancestor of the Ethiopian C viruses. A highly significant correlation
      between sampling years of the V3 sequences and their synonymous distances to the
      common ancestor was demonstrated. CONCLUSIONS: The increasing genetic
      heterogeneity together with stable consensus sequence of the Ethiopian HIV-1 C
      population demonstrates that evolution of the virus population is characterized
      by an unbiased expansion around a stationary consensus. Based on the rate of
      synonymous diversification of HIV-1 strains within the Ethiopian population, we
      were able to estimate 1983 (95% confidence interval, 1980-1984) as the year of
      HIV-1 C introduction into Ethiopia.

PMID- 11504989
TI  - 'Chemical condoms' for the prevention of HIV infection: evaluation of novel
      agents against SHIV(89.6PD) in vitro and in vivo.
AB  - BACKGROUND: Vaginal agents which are antiviral and/or inhibit the entry of HIV
      into the cell could prevent heterosexual transmission of HIV, and protect women
      who cannot negotiate condom use. METHODS: Four agents have been investigated for
      activity in vitro and in vivo against SHIV(89.6PD): two anionic polymers, dextrin
      2-sulphate (D2S) and PRO 2000 (P2K), and two virucidal agents; a non-ionic
      detergent, nonoxynol-9 (N9) and a cyclic peptide ionophore, gramicidin-D (GD).
      All four agents were investigated in rhesus macaques, using an intra-vaginal
      challenge of two inoculations of 1 x 104 50% tissue culture infectious doses
      (TCID)50 of SHIV(89.6PD). RESULTS: D2S, P2K, GD and N9 all inhibited SHIV(89.6PD)
      in vitro. In vivo, three out of four control macaques were infected as judged by
      viral culture, seroconversion, DNA and RNA PCR; infection was confirmed in four
      out of eight macaques pre-treated with P2K, two out of four pre-treated with D2S,
      one out of four pre-treated with N9, two out of four pre-treated with GD and four
      out of four pre-treated with D2S + GD, a combination additive in vitro.
      INTERPRETATION: D2S and PRO-2000, novel inhibitors of HIV entry, showed evidence
      of protection in vivo, comparable to that seen with the virucide, N9. These data,
      together with the results of phase I and phase II studies in healthy women which
      have shown minimal toxicity, support plans for a phase III efficacy trial of
      chemically simple inhibitors of HIV entry with low toxicity, for the prevention
      of HIV infection in women.

PMID- 11504990
TI  - HIV-1 seroconversion in United States Army active duty personnel, 1985-1999.
AB  - OBJECTIVE: To monitor HIV-1 infection trends among United States Army personnel,
      a predominantly young population group, tested between 1985 and 1999 for HIV-1
      infection. DESIGN: Demographic correlates of HIV-1 infection were assessed in the
      cohort via epidemiologic analysis. METHODS: Annual seroconversion incidence rates
      were calculated per 1000 person-years (PY) of follow-up. Poisson regression was
      used to assess demographic correlates of HIV-1 seroconversion risk. RESULTS:
      There were 1275 seroconverters among 2 004 903 active duty Army personnel
      accounting for 7 700 231 PY of follow-up. The HIV-1 incidence rate (IR) was
      0.17/1000 PY [95% confidence interval (CI), 0.16-0.17]. The highest IR was
      observed in the first year of testing (IR, 0.43/1000 PY; 95% CI, 0.33-0.52). The
      IR for male and female soldiers was 0.18/1000 PY and 0.08/1000 PY, respectively.
      HIV-1 incidence declined with age. Significant risk of HIV-1 seroconversion was
      associated with age [> 30 years old relative risk (RR), 1.51], race (Black RR,
      4.61; Hispanic RR, 2.76), gender (male RR, 3.12), marital status (unmarried RR,
      2.01) and rank (enlisted RR, 2.50). CONCLUSIONS: HIV-1 seroconversions in the US
      Army have been low and stable since the early 1990s. Continued HIV-1 incidence
      surveillance in the US Army provides information on the status of the epidemic in
      the Army, as well as important corroborative data on HIV-1 infections throughout
      the US.

PMID- 11504991
TI  - Absence of a recognizable seroconversion illness in Africans infected with HIV-1.
AB  - It is difficult to assess the proportion of individuals who experience an acute
      seroconversion illness after infection with HIV-1. We found that five out of 27
      recent HIV-1 seroconverters (18.5%) in a population-based cohort in rural Uganda
      and four out of 22 HIV-negative controls (18.2%) reported a flu-like illness.
      More symptoms were reported by seroconverters, but the duration of illness was
      similar in both groups. We found no association between symptoms and infection
      with HIV-1 subtype A or D.

PMID- 11504992
TI  - Decreased recovery of CD4 lymphocytes in older HIV-infected patients beginning
      highly active antiretroviral therapy.
AB  - Among virological responders, the area under the curve of the CD4 count minus
      baseline (AUCMB) after 3, 9, 15 and 18 months of highly active antiretroviral
      therapy (HAART) was less in individuals 55 years or older (P < 0.05). Fewer older
      individuals achieved increases of 50, 100, or over 150 CD4 cells/l. A random
      quadratic time course model estimated that the AUCMB decreased 35 cells/year for
      each 10 years of additional age during the first 12 months after HAART (P <
      0.005).

PMID- 11504993
TI  - Female sex and the use of anti-allergic agents increase the risk of developing
      cutaneous rash associated with nevirapine therapy.
AB  - To identify factors associated with cutaneous rash, we performed a retrospective
      multicentre analysis of HIV outpatients starting a highly active antiretroviral
      therapy regimen containing nevirapine. A total of 62 cutaneous adverse events
      were observed in 429 patients. Rash hazard was increased in women, by the
      prophylactic use of glucocorticoids or antihistaminics, and was reduced by
      escalating the initial dose of nevirapine. Women receiving glucocorticoids had a
      3 month cumulative probability of rash of 0.41.

PMID- 11504994
TI  - Non-nucleoside reverse transcriptase inhibitor failure impairs HIV-RNA responses
      to efavirenz-containing salvage antiretroviral therapy.
AB  - In a retrospective cohort study of salvage antiretroviral combination therapy
      including efavirenz, 60% of 51 patients were able to suppress HIV RNA by at least
      1 log10 or to less than 50 copies/ml. A lack of the previous use of non
      nucleoside reverse transcriptase inhibitors was the only factor predictive of
      response on multivariate analysis. No patient with a viral isolate with an
      increased IC50 to efavirenz by virtual phenotype had a virological response

PMID- 11504995
TI  - Indinavir did not increase the short-term risk of adverse cardiovascular events
      relative to nucleoside reverse transcriptase inhibitor therapy in four phase III
      clinical trials.
AB  - A retrospective person-time analysis of the randomized and non-randomized
      extension phases of four phase III trials was performed to assess the incidence
      of adverse cardiovascular events in 2680 HIV-infected patients receiving
      indinavir or nucleoside reverse transcriptase inhibitor therapy, or both. The
      observed rate of cardiovascular events was not increased in patients receiving
      indinavir-based regimens compared with therapy without a protease inhibitor.
      Extrapolation of these findings is limited by the brief length of therapy and the
      small number of cases.

PMID- 11504996
TI  - End-of-life care.

PMID- 11504997
TI  - Leber's hereditary optic neuropathy in the setting of nucleoside analogue
      toxicity.

PMID- 11504998
TI  - Possible bias of ascertainment in assessing chemoprophylaxis for
      cryptosporidiosis.

PMID- 11504999
TI  - Discontinuation of primary Pneumocystis carinii prophylaxis after reconstitution
      of CD4 cell counts in HIV-infected children.

PMID- 11505000
TI  - Response to highly active antiretroviral therapy in HIV-infected patients aged 60
      years or older after 24 months follow-up.

PMID- 11505017
TI  - Peroxisome proliferator-activated receptors (PPAR) and the mitochondrial aldehyde
      dehydrogenase (ALDH2) promoter in vitro and in vivo.
AB  - BACKGROUND: The aldehyde dehydrogenase 2 (ALDH2) promoter contains a nuclear
      receptor response element (NRRE) that represents an overlapping direct repeat-1
      (DR-1) and -5 (DR-5) element. Because DR-1 elements are preferred binding sites
      for peroxisome proliferator-activated receptors (PPARs), we tested the hypothesis
      that PPARs regulate ALDH2 expression. METHODS: We examined the ability of PPAR
      isoforms to bind to the ALDH2 NRRE in electrophoretic mobility shift assays,
      their ability to activate the transcription of promoter-reporter constructs
      containing this NRRE, the effect of PPAR ligands on ALDH2 expression in liver,
      and the role of the PPARalpha on the expression of ALDH2 by using PPARalpha-null
      mice. RESULTS: In vitro translated PPARs bound the ALDH NRRE with high affinity.
      Mutation of the NRRE indicated that binding was mediated by the DR-1 element.
      Cotransfection of PPAR expression plasmids showed that PPARalpha had no effect on
      expression of heterologous promoter constructs containing the NRRE. PPARgamma
      slightly induced expression, whereas PPARdelta repressed basal activity of the
      promoter and blocked induction by hepatocyte nuclear factor 4. Treatment of rats
      with the PPAR ligand clofibrate repressed expression of ALDH2 in rats fed either
      stock rodent chow or a low-protein diet. Consistent with the transfection data,
      expression of ALDH2 protein was not different in PPARalpha-null mice. Treatment
      of the mice with the PPARalpha agonist WY14643 slightly decreased the level of
      ALDH2 protein in both wild-type and PPARalpha-null mice, suggesting that the
      effect of WY14643 was not mediated by the receptor. CONCLUSIONS: These data
      indicate that ALDH2 is not part of the battery of lipid metabolizing enzymes and
      proteins regulated by PPARalpha

PMID- 11505018
TI  - Serotonin transporter promoter polymorphism genotype is associated with
      behavioral disinhibition and negative affect in children of alcoholics.
AB  - BACKGROUND: Serotonergic (5-HT) dysfunction has been implicated in the etiology
      of both behavioral disinhibition (BD) and negative affect (NA). This work extends
      our previous finding of relationships between whole blood 5-HT and both BD and NA
      in pubescent, but not prepubescent, children of alcoholics and continues
      examination of a hypothesized role of 5-HT dysfunction in alcoholism risk. The
      long and short (L and S) variants of the 5-HT transporter gene-linked polymorphic
      region (5-HTTLPR) are responsible for differing transcriptional efficiencies in 5
      HT uptake. Although associations have been found between the SS 5-HTTLPR genotype
      and severe alcoholism and neuroticism, recent reports describe relationships
      between the LL genotype and both low level of response to alcohol and alcoholism
      diagnosis and a predominance of the LL genotype in early-onset alcoholics.
      METHODS: This report is from an ongoing prospective study of the development of
      risk for alcoholism and other problematic outcomes in a sample of families
      classified by father's alcoholism subtype. This study examines relationships
      between 5-HTTLPR genotype and both child BD (Child Behavior Checklist Aggressive
      Behavior) and NA (Child Behavior Checklist Anxious/Depressed) in offspring from
      47 families. RESULTS: Results showed significantly higher levels of BD and NA in
      the 16 children with the LL genotype than the 46 SS or SL children. CONCLUSIONS:
      Behaviors of undercontrol, which occur at increased rates in children of
      alcoholics, may be genetically influenced through the regulation of the 5-HT
      transporter. Due to the small sample size and the preliminary nature of our
      findings, replication is necessary.

PMID- 11505019
TI  - P3 event-related potential, dopamine D2 receptor A1 allele, and sensation-seeking
      in adult children of alcoholics.
AB  - BACKGROUND: Research has indicated a close relationship between the P3 event
      related potential and the dopamine D2 receptor A1 allele in individuals at high
      risk for alcoholism. Other research has suggested an association between the
      dopamine D2 receptor A1 allele and sensation-seeking. In this study, we further
      examined the relationships between the P3, the A1 allele, and sensation-seeking
      in a sample of nonalcoholic adult children of alcoholics. METHODS: Participants
      (n = 57; range, 19-30 years; 41 women), who performed a visual novelty oddball
      task to elicit the P3, were asked to fill in personality questionnaires,
      including Zuckerman's Sensation-Seeking Scale, and were classified according to
      the presence of the dopamine D2 receptor A1 allele. The effects of sex, age, and
      socioeconomic status were assessed to determine whether these variables affected
      the relations between the P3, the A1 allele, and sensation-seeking. RESULTS: A
      small P3 amplitude was associated with high sensation-seeking, particularly with
      high disinhibition. The presence of the A1 allele was also associated with high
      disinhibition, but only in men. By contrast, P3 amplitudes and latencies were not
      associated with the presence of the A1 allele. CONCLUSIONS: Although a small P3
      amplitude, high sensation-seeking, and the presence of the A1 allele were all
      associated with alcoholism risk, these findings indicate that these three
      characteristics together do not reflect a common risk factor in alcoholism.

PMID- 11505020
TI  - Chronic ethanol enhances adenosine antiadrenergic actions in the isolated rat
      heart.
AB  - BACKGROUND: Chronic alcohol consumption elicits an increase in catecholamine
      release, which may be detrimental to heart function. Adenosine attenuates
      adrenergic stimulation via an adenosine receptor-mediated antiadrenergic action.
      This study investigated the effect of ethanol on adenosine antiadrenergic actions
      and adenosine release in the rat heart. METHODS: Rats were pair-fed a liquid diet
      with or without ethanol for 4 weeks or 8 months. Hearts were isolated for
      determination of contractile function, and coronary effluents were collected for
      adenosine content. Dose-response relationships for phenylisopropyladenosine (PIA)
      were determined for hearts adrenergically stimulated by isoproterenol.
      Experiments were also conducted with normal hearts with or without ethanol (25
      mM) administered acutely. The effect of PIA on adenylyl cyclase activities of
      adrenergic-stimulated crude membrane preparations obtained from alcoholic and
      nonalcoholic hearts was determined. RESULTS: Acute ethanol reduced basal
      adenosine release by 39%, but it did not significantly decrease adenosine release
      during adrenergic stimulation. In hearts chronically treated with ethanol for 4
      weeks, adenosine release values before and during adrenergic stimulation were
      significantly reduced from control values. After 8 months of ethanol, adenosine
      release was similar with or without adrenergic stimulation. PIA 50% inhibiting
      concentration (IC50) values for contractile function were reduced from pair-fed
      control values. Acute ethanol did not significantly change the PIA IC50 value.
      Chronic ethanol reduced the PIA IC50 for adenylyl cyclase by 96%. CONCLUSIONS:
      Chronic ethanol treatment increases the antiadrenergic action of adenosine by
      mechanisms that seem independent of changes in adenosine concentration.
      Therefore, adenosine-induced cardioprotection against increased catecholamine
      stimulation is enhanced by ethanol.

PMID- 11505021
TI  - Relationship of brain ethanol metabolism to the hypnotic effect of ethanol. I:
      Studies in outbred animals.
AB  - BACKGROUND: This study was designed to investigate the relationship between the
      ethanol-oxidizing capacity of the brain, accumulation of acetaldehyde, and
      ethanol-induced hypnosis in animals in vivo. METHODS: Randomly outbred albino
      rats were treated with ethanol, and the duration of ethanol-induced loss of the
      righting response (sleep time) was measured. They were killed 2 weeks later
      (without further in vivo administration of ethanol), and brain homogenates were
      prepared to measure the accumulation of acetaldehyde from ethanol added in vitro.
      In a similar way, we determined the sleep time and, 5 days later, the rates of
      acetaldehyde accumulation in brains of heterogeneous mice. RESULTS: Significant
      correlations between the duration of ethanol-induced sleep and acetaldehyde
      accumulation in vitro were found. The Km value of the process of acetaldehyde
      accumulation was lower in long-sleeping, as compared with short-sleeping, rats. A
      similar result was also obtained in genetically heterogeneous mice. Animals with
      a longer duration of ethanol-induced sleep had a higher level of the accumulation
      of ethanol-derived acetaldehyde in brain homogenates, as compared with the short
      sleeping mice. Rats and mice with the intermediate duration of ethanol-induced
      sleep had an intermediate value of acetaldehyde accumulation in brain
      homogenates. There was no correlation between brain catalase activity and ethanol
      induced loss of the righting response in either the rats or the mice.
      CONCLUSIONS: This study is a direct demonstration of the positive correlation
      between ethanol-derived acetaldehyde accumulation in vitro in the brain and a
      central (behavioral) effect of alcohol in outbred rats and mice in vivo.

PMID- 11505022
TI  - Relationship of brain ethanol metabolism to the hypnotic effect of ethanol. II:
      Studies in selectively bred rats and mice.
AB  - BACKGROUND: To clarify the role of brain acetaldehyde in the hypnotic effect of
      ethanol, we compared the ethanol-oxidizing capacity (rate of acetaldehyde
      accumulation) and catalase and aldehyde dehydrogenase activity in the brains of
      animals genetically selected for different sensitivities to the hypnotic effect
      of ethanol. METHODS: We used high, low, or control alcohol-sensitive rats (HAS,
      LAS, and CAS) and short- and long-sleep mice (SS and LS), as well as SS x LS
      recombinant inbred mice with known strain differences in mean duration of ethanol
      induced sleep. We studied the rate of accumulation of acetaldehyde from ethanol
      in brain homogenates of these animals and correlated those values with their
      hypnotic sensitivity to ethanol. RESULTS: Acetaldehyde accumulation from ethanol
      was significantly higher in the brain homogenates from HAS rats and LS mice with
      high sensitivity to the hypnotic effect of ethanol in vivo, compared with LAS
      rats and SS mice with low sensitivity to ethanol. A correlation was found between
      the duration of ethanol-induced sleep and the in vitro rate of accumulation of
      ethanol-derived acetaldehyde in the brains of recombinant SS x LS mice strains.
      There was no correlation of sleep time with brain catalase levels. There were no
      line differences in brain catalase or aldehyde dehydrogenase or in alcohol or
      aldehyde dehydrogenase activity in livers of LAS, CAS, and HAS rats or in SS and
      LS mice. CONCLUSIONS: A correlation between the brain acetaldehyde accumulation,
      but not catalase levels, and the central effect of ethanol was demonstrated in
      animals genetically differing in initial sensitivity to the hypnotic effect of
      ethanol.

PMID- 11505023
TI  - Fetal and infantile alcohol-mediated associative learning in the rat.
AB  - BACKGROUND: Infant rats express conditioned responses to an odor experienced
      prenatally as a chemosensory cue associated with moderate alcohol intoxication.
      This study examined postnatal intake of a chemosensory cue (cineole) that had
      been paired with alcohol's unconditioned effects. It also tested the interaction
      between prenatal association and postnatal conditioning with cineole and alcohol.
      METHODS: Pregnant female rats intubated with cineole were given ethanol (EtOH).25
      or 4.0 hr later. Other groups received only water or water paired with ethanol.
      During postnatal day 15 (PD15), infant consumption of cineole solution was
      assessed. After the cineole drinking test, pups were intubated with EtOH or water
      to assess infant conditioning. On PD16, all pups were tested for mouthing to milk
      alone or to a milk-cineole solution. RESULTS: Statistical analysis confirmed
      fetal associative conditioning attributable to the unconditioned effects of
      prenatal alcohol. Fetuses given explicit pairings of cineole and alcohol ingested
      less cineole on PD15 than control fetuses given a 4-hr interval between cineole
      and alcohol. On PD16, consumption of cineole was significantly increased by
      prenatal exposure to cineole. Teratogenic effects of this dose of prenatal
      alcohol did not affect postnatal associative or nonassociative behavior.
      CONCLUSIONS: Prenatal associative learning can be established through temporal
      contiguity between fetal chemosensory stimulation and alcohol's unconditioned
      properties. This associative memory survives to infancy and modulates intake
      patterns and behavioral reactivity to substances that were prenatally paired with
      alcohol intoxication.

PMID- 11505024
TI  - Chronic daily ethanol and withdrawal: 2. Behavioral changes during prolonged
      abstinence.
AB  - BACKGROUND: Our previous investigations have suggested that alcohol abuse may
      induce persistently compromised hypothalamo-pituitary-adrenal (HPA) function,
      which could increase risk for subsequent alcohol abuse. The apparent similarity
      of chronic alcohol abuse-induced HPA defects to the compromised HPA functions
      associated with posttraumatic stress disorder and atypical depression also
      suggest potential common mechanisms shared with varied neurobehavioral disorders.
      Accordingly, we have investigated persistent behavioral effects of previous
      repetitive daily ethanol consumption and withdrawal. METHODS: Male Sprague-Dawley
      rats received either daily ad libitum chow, ad libitum liquid diet containing
      ethanol, or pair-fed isocaloric control liquid diet. The ethanol was gradually
      introduced over 4 weeks, maintained at 5% w/v for four subsequent weeks, and then
      gradually removed over 1 week. RESULTS: Four weeks after removal of ethanol from
      the diet, the previously ethanol-consuming rats exhibited greater (p < 0.05)
      evidence of anxiety in the elevated plus-maze test and in the novel cork-gnawing
      test, as well as greater (p < 0.05) locomotor response to a novel environment,
      compared with controls. CONCLUSIONS: These results suggest that repetitive daily
      alcohol consumption and withdrawal can induce not only persistent defects in HPA
      function, but also persistent increases in anxiety and behavioral responsiveness
      to novelty, all consistent with characteristics of abstinent alcoholics as well
      as with rats that self-administer increased amounts of alcohol and other drugs of
      abuse. This suggests that alcohol abuse can induce persistent common or
      interacting changes in neuroendocrine and behavioral responses that may increase
      risk for subsequent abuse.

PMID- 11505025
TI  - Effect of naloxone on appetitive and consummatory phases of ethanol self
      administration.
AB  - BACKGROUND: The opioid system has been implicated in ethanol self-administration.
      Morphine, an opiate agonist, can sometimes increase the amount of ethanol
      consumed, and opiate antagonists such as naloxone and naltrexone decrease the
      amount of ethanol consumed in both animals and humans. The objective of this
      study was to examine the effect of naloxone on appetitive (or seeking) and
      consummatory behaviors by using an operant model developed to separate these two
      phases of self-administration. METHODS: Intraperitoneal injections of naloxone
      (0.3-10 mg/kg) or vehicle were given before operant self-administration sessions
      to assess the effect on lever pressing (appetitive behavior) and subsequent
      consumption. Effects were measured in two groups of rats: one self-administered a
      3% sucrose solution and the other a 10% ethanol solution. RESULTS: Naloxone dose
      dependently decreased ethanol and sucrose consumption by an earlier cessation of
      drinking in the session compared with vehicle injection days. There were some
      effects on appetitive responding after treatment with naloxone, but none was
      statistically significant. CONCLUSIONS: Naloxone may decrease ethanol self
      administration by decreasing the postingestive or pharmacological effects of
      alcohol. This model provides a new method for examining the effects of potential
      pharmacotherapeutics on alcohol self-administration behavior.

PMID- 11505026
TI  - Psychopathology in pregnant drug-dependent women with and without comorbid
      alcohol dependence.
AB  - BACKGROUND: Individuals with comorbid alcohol and drug use disorders are at
      particularly high risk for a variety of problems, including other psychiatric
      disorders. In general, patients with comorbid alcohol and drug dependence tend to
      have more severe dependence problems and often have poorer treatment outcomes
      than individuals with single disorders. For treatment-seeking pregnant women,
      psychiatric comorbidity can lead to relapse and premature treatment dropout, with
      adverse consequences to mother and infant. METHODS: Psychopathology, as measured
      by the Minnesota Multiphasic Personality Inventory-Revised (MMPI-2), was examined
      in 170 pregnant women admitted to a comprehensive treatment program for cocaine
      or opiate dependence. Most were single (75%) and African American (80%), with a
      mean age of 29 years. Thirty-six met DSM-III-R criteria for both alcohol and drug
      dependence (alcohol positive), whereas 134 were drug dependent only (alcohol
      negative). RESULTS: Alcohol-positive women had higher levels of psychopathology
      than alcohol-negative women, with higher scores on scales 2 (Depression), 4
      (Psychopathic Deviance), 8 (Schizophrenia), and 0 (Social Introversion; p <
      0.05). The mean MMPI-2 profile for alcohol-positive women was 2-4-8 (Depression
      Psychopathic Deviance-Schizophrenia; all T-scores > 65), whereas alcohol-negative
      women had only a scale 4 increase. CONCLUSIONS: Results suggest that pregnant,
      drug-dependent women with comorbid alcohol dependence present for treatment with
      greater psychopathology and thus may require more intense interventions than
      pregnant, drug-dependent women without comorbid alcohol dependence. Alcohol use
      by pregnant women is particularly important to address in treatment, because
      alcohol is a known teratogen associated with mental retardation and behavioral
      problems.

PMID- 11505027
TI  - Comparison of the adaptive functioning of children prenatally exposed to alcohol
      to a nonexposed clinical sample.
AB  - BACKGROUND: Several studies show impairments in the social and adaptive behaviors
      of children prenatally exposed to alcohol. However, there remains limited
      consensus on whether the alcohol exposure directly affects social functioning or
      whether its effect is mediated by deficits in IQ. In addition, no studies have
      investigated whether deficits in social functioning are significantly more
      pronounced in children prenatally exposed to alcohol than in children referred to
      psychiatric treatment who were not prenatally exposed. We explored the effect of
      alcohol exposure on social and adaptive functioning and explored whether or not
      social and adaptive functioning are significantly more impaired in children
      prenatally exposed to alcohol than in a clinical sample of children. METHODS: A
      sample of 33 alcohol-exposed children was compared with a sample of 33 clinic
      referred nonexposed children. The groups were compared on measures of
      communication, daily living skills, and socialization. The groups were matched on
      sex, age, IQ, and outpatient or inpatient status. RESULTS: Analyses revealed that
      the prenatally alcohol-exposed children did not differ significantly from the
      nonexposed children in any of the domains of adaptive functioning. However, with
      age, exposed children showed a more rapid decline in socialization standard
      scores compared with the nonexposed clinical sample. CONCLUSIONS: Young children
      who were exposed to alcohol prenatally show deficits in all domains of adaptive
      functioning. Although these deficits do not seem to differ from those exhibited
      by young children with psychiatric problems but no prenatal exposure, deficits in
      socialization behavior of prenatally exposed children may become more significant
      with age.

PMID- 11505028
TI  - Effect of chronic ethanol exposure on female rat reproductive cyclicity and
      hormone secretion.
AB  - BACKGROUND: Ethanol exposure impairs mammalian reproductive function. However,
      the mechanisms are not fully understood. METHODS: Adult female rats were given an
      ethanol or a calorically matched control diet. A third group was given a liquid
      nonethanol diet. Half the animals were killed at 2 weeks (short chronic) and the
      other half at 2 months (long chronic), all on the day of proestrous on the basis
      of daily vaginal smears. RESULTS: The major effect of ethanol feeding was
      disruption in the estrous cycle. Although all of the pair-fed animals continued
      to cycle, 40% of the ethanol rats in the short chronic study had disruption of
      their cycles. In the long chronic study, 83% of the ethanol animals had abnormal
      cycling, in contrast to 16% of the pair-fed controls. The nature of the cycle
      disruption was prolongation of diestrous, with an increased time interval between
      proestrous surges. In four ethanol-fed rats, there was complete cessation of the
      estrous cycle. However, ethanol did not decrease ovarian or uterine weight.
      Ethanol significantly increased serum estradiol in the short chronic but not long
      chronic study, whereas progesterone was unchanged. Ethanol did cause a
      significant reduction in circulating insulin-like growth factor. CONCLUSIONS: The
      major effect of both short chronic and long chronic ethanol exposure was
      disruption of the estrous regularity, leading to a decreased number of proestrous
      surges. Part of the mechanism of this disruption might be a transient estrogen
      increase or a decrease in circulating insulin-like growth factor.

PMID- 11505029
TI  - Electroencephalogram spectral characteristics after alcohol ingestion in Japanese
      men with aldehyde dehydrogenase-2 genetic variations: comparison with peripheral
      changes.
AB  - BACKGROUND: Electroencephalographic (EEG) activity induced by alcohol ingestion
      may be influenced by individual differences in alcohol metabolism. Specifically,
      an absence of the low Km isozyme of aldehyde dehydrogenase (ALDH), found in many
      Asians, may be related to alterations of EEGs. METHODS: EEG power spectral
      changes induced by 0.4 ml/kg of alcohol ingestion were compared in two groups of
      Japanese subjects: NN (ALDH2*1/1, n = 19) and ND (ALDH2*2/1, n = 12). Peripheral
      changes in heart rate and facial skin temperature were evaluated after the same
      treatment. Blood ethanol, acetaldehyde, and catecholamine levels were determined
      to evaluate mediation of the ethanol metabolite, acetaldehyde, and its indirect
      action on EEGs through the effects on peripheral systems. RESULTS: As expected,
      blood acetaldehyde was about 10-fold higher in the ND subjects compared with the
      NN subjects during the postingestion period. Ethanol produced characteristic EEG
      changes during and after ingestion. The ND subjects, however, displayed brief
      periods of decrease in slow alpha immediately after alcohol ingestion and showed
      no long-term EEG changes. The EEG changes were parallel to peripheral changes.
      CONCLUSIONS: The lack of increased EEG power in the ND subjects may be partly
      mediated by a direct action of the high concentration of acetaldehyde in the
      central nervous system that penetrates from the peripheral blood. In addition to
      this direct action of acetaldehyde, an indirect action, such as feedback from
      peripheral changes, might prevent the characteristic increase in alpha and beta
      power observed in the NN subjects.

PMID- 11505030
TI  - Effects of alcohol consumption on indices of iron stores and of iron stores on
      alcohol intake markers.
AB  - BACKGROUND: Alcohol increases body iron stores. Alcohol and iron may increase
      oxidative stress and the risk of alcohol-related liver disease. The relationship
      between low or "safe" levels of alcohol use and indices of body iron stores, and
      the factors that affect the alcohol-iron relationship, have not been fully
      characterized. Other aspects of the biological response to alcohol use have been
      reported to depend on iron status. METHODS: We have measured serum iron,
      transferrin, and ferritin as indices of iron stores in 3375 adult twin subjects
      recruited through the Australian Twin Registry. Information on alcohol use and
      dependence and smoking was obtained from questionnaires and interviews. RESULTS:
      Serum iron and ferritin increased progressively across classes of alcohol intake.
      The effects of beer consumption were greater than those of wine or spirits.
      Ferritin concentration was significantly higher in subjects who had ever been
      alcohol dependent. There was no evidence of interactions between HFE genotype or
      body mass index and alcohol. Alcohol intake-adjusted carbohydrate-deficient
      transferrin was increased in women in the lowest quartile of ferritin results,
      whereas adjusted gamma-glutamyltransferase, aspartate aminotransferase, and
      alanine aminotransferase values were increased in subjects with high ferritin.
      CONCLUSIONS: Alcohol intake at low level increases ferritin and, by inference,
      body iron stores. This may be either beneficial or harmful, depending on
      circumstances. The response of biological markers of alcohol intake can be
      affected by body iron stores; this has implications for test sensitivity and
      specificity and for variation in biological responses to alcohol use.

PMID- 11505031
TI  - Influence of alcohol intake on risk for increased low-density lipoprotein
      cholesterol in middle-aged Japanese men.
AB  - BACKGROUND: Decreased low-density lipoprotein (LDL) cholesterol in chronic
      alcoholics is well known. However, the importance of light to moderate alcohol
      consumption is less certain. METHODS: We investigated the association of alcohol
      intake with risk for increased LDL cholesterol over 5 years in a cohort of 933
      Japanese male office workers aged 35 to 54 years who had LDL cholesterol levels
      less than 140 mg/dl and were not taking medication for dyslipidemia,
      hypertension, diabetes, liver disease, or hyperuricemia at study entry. Incident
      increased LDL cholesterol was defined by an LDL cholesterol level of 140 mg/dl or
      more or use of medication for dyslipidemia. Each individual's slope for LDL
      cholesterol was also calculated with a simple linear regression model. RESULTS:
      Three hundred twenty-one men developed increased LDL cholesterol during 3785
      person-years of follow-up. After controlling for potential predictors of
      increased LDL cholesterol, the relative risk for increased LDL cholesterol
      compared with nondrinkers was 0.89 for those who drank 0.1 to 22.9 g/day of
      ethanol, 0.74 for those who drank 23.0 to 45.9 g/day of ethanol, 0.64 for those
      who drank 46.0 to 59.9 g/day of ethanol, and 0.54 for those who drank 69.0 g/day
      or more of ethanol (p < 0.001). Slopes of LDL cholesterol level decreased
      significantly as alcohol intake increased. From multiple linear regression
      analyses, alcohol intake remained as an independent negative factor for slopes of
      LDL cholesterol level. CONCLUSIONS: Alcohol intake is negatively associated with
      development of increased LDL cholesterol in middle-aged Japanese men.

PMID- 11505032
TI  - Alcohol-mediated Purkinje cell loss in the absence of hypoxemia during the third
      trimester in an ovine model system.
AB  - BACKGROUND: Although the mechanisms that underlie fetal alcohol-induced neuronal
      loss have not been determined, hypoxia/hypoxemia has been considered a leading
      candidate. This study was designed to test the hypothesis that neuronal loss
      could occur in the developing brain in the absence of fetal hypoxemia. METHODS:
      Three groups of pregnant sheep were used: a control group, a binge-drinking
      group, and a pair-fed group. The alcohol and pair-fed animals were anesthetized
      on day 113 of pregnancy, and the mothers and fetuses were instrumented with
      arterial and venous catheters. All animals were killed on day 133. Stereological
      cell counting techniques were used to estimate the total number of Purkinje cells
      in the fetal cerebellum. RESULTS: Peak maternal and fetal blood alcohol
      concentrations did not produce fetal hypoxemia. Nevertheless, there was a 25%
      loss of Purkinje cells of the cerebellum in the alcohol-exposed fetuses compared
      with that in the pair-fed controls. The loss of neurons was not accompanied by
      microencephaly or a concomitant decrease in either cerebellar weight or volume of
      the fetal cerebellum. CONCLUSIONS: Neuronal loss can be observed after alcohol
      exposure during the third trimester equivalent in fetal sheep in the absence of
      alcohol-induced hypoxemia. Furthermore, cell loss in the absence of deficits in
      gross brain weight or regional brain volume indicates that the lack of gross
      brain volume deficits from magnetic resonance imaging techniques is not a
      reliable indication that the brain is unaffected by the alcohol exposure.

PMID- 11505033
TI  - Inhibition of insulin-like growth factor-I signaling by ethanol in neuronal
      cells.
AB  - BACKGROUND: Ethanol inhibits insulin-like growth factor-I receptor (IGF-IR)
      activation. However, the potency of ethanol for inhibition of the IGF-IR and
      other receptor tyrosine kinases varies considerably among different cell types.
      We investigated the effect of ethanol on IGF-I signaling in several neuronal cell
      types. METHODS: IGF-I signaling was examined in SH-SY5Y neuroblastoma cells,
      primary cultured rat cerebellar granule neurons, and rat NG-108 neuroblastoma x
      glioma hybrids. The tyrosine phosphorylation of IGF-IR, IRS-2, Shc, and p42/p44
      MAP kinase (MAPK), and the association of Grb-2 with Shc, were examined by
      immunoprecipitations and Western blotting. RESULTS: IGF-I-mediated tyrosine
      phosphorylation of MAPK was inhibited by ethanol in all cell lines. IGF-IR
      autophosphorylation was markedly inhibited by ethanol in SH-SY5Y cells, was only
      mildly inhibited in cerebellar granule neurons, and was unaffected in rat NG-108
      cells. In vitro tyrosine autophosphorylation of immunopurified IGF-IR obtained
      from all cell lines was inhibited by ethanol. There was also differential ethanol
      sensitivity of IRS-2 and Shc phosphorylation, and the association of Shc with IRS
      2, among the different cell types. CONCLUSIONS: The findings demonstrate that IGF
      I-mediated MAPK activation is a sensitive target of ethanol in diverse neuronal
      cell types. The data are consistent with ethanol-induced inhibition of IGF-IR
      activity, although the extent of IGF-IR tyrosine autophosphorylation per se is a
      poor marker of the inhibitory action of ethanol on this receptor. Furthermore,
      despite uniform inhibition of MAPK in the different neuronal cell types, tyrosine
      phosphorylation of proximal mediators of the IGF-IR are differentially inhibited
      by ethanol.

PMID- 11505034
TI  - Fetal and maternal sheep hypothalamus pituitary adrenal axis responses to chronic
      binge ethanol exposure during the third trimester equivalent.
AB  - BACKGROUND: We tested the hypothesis that in utero ethanol exposure results in
      changes in fetal and maternal adrenocorticotropin (ACTH) and cortisol during the
      third trimester equivalent, by using a chronically instrumented fetal sheep
      model. METHODS: Pregnant ewes received saline or ethanol intravenously 3
      consecutive days per week from day 109 to day 132 of gestation. Fetal and
      maternal blood samples were collected on days 118 and 132. RESULTS: Maternal and
      fetal ACTH and cortisol values increased on days 118 and 132 of gestation in
      response to ethanol infusions that created blood ethanol concentrations (BECs)
      that are easily achievable by human drinkers. Peak ACTH and cortisol values were
      detected 30 to 60 min after peak BECs were achieved. CONCLUSIONS: Chronic ethanol
      exposure during the third trimester equivalent in sheep resulted in repeated
      activation of the hypothalamus-pituitary-adrenal axis in both the mother and
      fetus. Temporally, the patterns of maternal and fetal responses to ethanol
      infusion were similar. We conclude that ovine maternal ethanol exposure during
      the third trimester equivalent increases fetal ACTH and cortisol concentrations,
      hormonal responses that may play a role in mediating alcohol-related birth
      defects.

PMID- 11505035
TI  - Nicotine decreases blood alcohol concentration in neonatal rats.
AB  - BACKGROUND: Our previous findings suggested that the intragastric
      coadministration of alcohol and nicotine to neonatal rats resulted in a
      significant decrease from the predicted peak blood alcohol concentration (BAC).
      We hypothesized that the coadministration of alcohol and nicotine would produce a
      nicotine dose-related decrease in peak BAC and a change in the BAC time curve
      profile. METHODS: Sprague-Dawley rat pups were given alcohol and nicotine
      simultaneously via intragastric infusion. Two sets of nicotine doses were used in
      two independent studies. The low doses of nicotine were examined after the study
      of high doses of nicotine administration because of the possible ceiling effects
      from these nicotine doses on lowering BACs. RESULTS: The results not only
      confirmed that the peak BAC was lowered by nicotine, but also generated new
      findings showing that the profile of BAC time curve was affected by these doses
      of nicotine. Concerns about possible ceiling effects led us to conduct another
      experiment to examine the effects of lower doses of nicotine on BACs. Those
      results showed a significant decline in BACs after cotreatment with 0.5 or 1
      mg/kg nicotine and less robust changes on the BAC curve profiles. Although the
      nicotine dose at 0.25 mg/kg/day did not affect significantly the overall BAC
      profile, it did lower the peak BAC. CONCLUSIONS: Nicotine is capable of lowering
      the peak BAC among neonatal rat pups. Furthermore, the pattern of the BAC time
      curve seems to be more affected by high doses of nicotine.

PMID- 11505036
TI  - Effect of chronic ethanol ingestion on alveolar type II cell: glutathione and
      inflammatory mediator-induced apoptosis.
AB  - BACKGROUND: In septic patients, chronic alcohol abuse increases the incidence of
      the acute respiratory distress syndrome, a syndrome that requires alveolar type
      II cell proliferation and differentiation for repair of the damaged alveolar
      epithelium. We previously showed in a rat model that chronic ethanol ingestion
      decreased the antioxidant glutathione (GSH) in type II cells and exacerbated
      endotoxin-mediated acute lung injury. We hypothesized that this GSH depletion by
      ethanol, particularly mitochondrial GSH, predisposed type II cells to
      inflammatory mediator-induced apoptosis. METHODS: Adult male rats were fed the
      Lieber-DeCarli diet for 2, 6, or 16 weeks. Alveolar type II cells were then
      isolated and treated with hydrogen peroxide or TNF-alpha. The effect on
      glutathione (cytosolic and mitochondrial), apoptotic events, and necrosis were
      determined. In other studies, rats were fed ethanol for 6 weeks and were treated
      with endotoxin and apoptosis of type II cells determined by the TUNEL method.
      RESULTS: Chronic ethanol ingestion alone resulted in a progressive decrease in
      mitochondrial GSH and a progressive increase in the basal apoptosis and necrosis
      rate (p < or = 0.05). Furthermore, there was a progressive increase in the
      sensitivity of the cells to H2O2 or TNF-alpha induced cytochrome c release,
      caspase 3 activation, apoptosis, and necrosis (p < or = 0.05). Finally, there was
      a 2-fold increase in apoptotic type II cells in vivo when chronic ethanol
      ingestion was superimposed on endotoxemia. CONCLUSIONS: These results suggested
      that chronic ethanol ingestion resulted in a progressive depletion of
      mitochondrial GSH and sensitization of type II cells to inflammatory mediator
      induced apoptosis and necrosis. These effects may be particularly relevant during
      acute stress when proliferation and differentiation of these cells are critical
      to repair of the damaged alveolar epithelium and may have important ramifications
      for the treatment of acute respiratory distress syndrome in patients with a
      history of alcohol abuse.

PMID- 11505038
TI  - Induction and maintenance of ethanol self-administration in cynomolgus monkeys
      (Macaca fascicularis): long-term characterization of sex and individual
      differences.
AB  - BACKGROUND: Investigations of oral ethanol self-administration in nonhuman
      primates have revealed important parallels with human alcohol use and abuse, yet
      many fundamental questions concerning the individual risk to, and the biological
      basis of, excessive ethanol consumption remain unanswered. Moreover, many
      conditions of access to ethanol in nonhuman primate research are largely
      unexplored. This set of experiments extends within- and across-session exposure
      to ethanol to more fully characterize individual differences in oral ethanol self
      administration. METHODS: Eight male and eight female adult cynomolgus monkeys
      (Macaca fascicularis) were exposed to daily oral ethanol self-administration
      sessions for approximately 9 months. During the first 3 months, a fixed-time (FT)
      schedule of food delivery was used to induce the consumption of an allotted dose
      of ethanol in 16-hr sessions. Subsequently, the FT schedule was suspended, and
      ethanol was available ad libitum for 6 months in 16- or 22-hr sessions. RESULTS:
      Cynomolgus monkeys varied greatly in their propensity to self-administer ethanol,
      with sex and individual differences apparent within 10 days of ethanol exposure.
      Over the last 3 months of ethanol access, individual average ethanol intakes
      ranged from 0.6 to 4.0 g/kg/day, resulting in blood ethanol concentrations from 5
      to 235 mg/dl. Males drank approximately 1.5-fold more than females. In addition,
      heavy-, moderate-, and light-drinking phenotypes were identified by using daily
      ethanol intake and the percentage of daily calories obtained from ethanol as
      criteria. CONCLUSIONS: Cynomolgus monkeys displayed a wide intersubject range of
      oral ethanol self-administration with a procedure that used a uniform and
      prolonged induction that restricted early exposure to ethanol and subsequently
      allowed unlimited access to ethanol. There were sex and stable individual
      differences in the propensity of monkeys to consume ethanol, indicating that this
      species will be important in characterizing risk factors associated with heavy
      drinking phenotypes.

PMID- 11505039
TI  - Direct evidence for a cause-effect link between ethanol potentiation of GABA(A)
      receptor function and intoxication from hyperbaric studies in C57, LS, and SS
      mice.
AB  - BACKGROUND: This article uses a direct ethanol antagonist, increased atmospheric
      pressure, to further test the causative link between ethanol potentiation of
      gamma-aminobutyric acid (GABA) type A receptor function and ethanol's behavioral
      effects. This was done by determining whether initial biochemical findings in
      long-sleep (LS) mice extended to other genotypes and whether the previously
      reported insensitivity of short-sleep (SS) mice to pressure antagonism of ethanol
      induced loss of righting reflex extended to a nonselected ethanol-induced
      behavior. METHODS: The effects of 12 times normal atmospheric pressure of helium
      oxygen gas (heliox) versus ethanol (25-200 mM) potentiation of GABA-activated Cl-
      uptake in brain membranes (microsacs) from C57, LS, and SS mice were tested by
      using a 36Cl- flux assay. The effects of pressure versus ethanol's (2 g/kg)
      anticonvulsant effect in SS mice were tested by using time to onset of isoniazid
      induced myoclonic seizures. RESULTS: Exposure to 12 times normal atmospheric
      pressure heliox antagonized ethanol potentiation of GABA-activated Cl- uptake in
      all three genotypes across a range of ethanol concentrations that cause ethanol's
      behavioral and anesthetic effects. Pressure did not affect baseline receptor
      function. The threshold for initiating ethanol potentiation differed between
      genotypes in accordance with their behavioral sensitivities to ethanol (C57 and
      LS, < or =25 mM; SS, >50 mM). Pressure antagonized ethanol's anticonvulsant
      effect in SS mice. CONCLUSIONS: The results add important direct evidence
      supporting the hypothesis that ethanol potentiation of GABA(A) receptor function
      is an initial action of ethanol causing its behavioral effects. These findings
      also provide insight into possible effects of selective breeding on GABA(A)
      receptor function.

PMID- 11505040
TI  - Role of nitric oxide in ethanol-induced up-regulation of muscarinic acetylcholine
      receptors in SH-SY5Y cells.
AB  - BACKGROUND: Ethanol abuse has been shown to up-regulate muscarinic acetylcholine
      receptors (mAChRs) in the central nervous system, both in vivo and in vitro, but
      the detailed mechanisms for this action are not known. Recent studies suggest
      that the actions of ethanol in several biological systems involve nitric oxide
      (NO) pathways. The aim of this work was therefore to determine whether the
      effects of long-term ethanol treatment on mAChRs involved actions upon NO
      pathways in a well defined cell culture system. METHODS: Human neuroblastoma SH
      SY5Y cells were used as an in vitro model system. The time- and dose-dependent
      effects of ethanol on endogenous NO production, as well as the effects of the NO
      donor 3-morpholino-sydnonimine-chloride and of the neuronal NO synthase (nNOS)
      inhibitor N(omega)-propyl-L-arginine on mAChR number and on ethanol effects upon
      these receptors, were studied. RESULTS: Ethanol time- and dose-dependently
      decreased the production of NO in the cells. Exogenous NO decreased the number of
      mAChRs and totally blocked the effects of ethanol upon these receptors.
      Inhibition of nNOS up-regulated the number of mAChRs, but this effect was not
      additive to the effects of ethanol. CONCLUSIONS: The results of this study
      suggest that the number of cell-surface mAChRs in SH-SY5Y cells may be correlated
      with changes in NO levels. The number of cell surface mAChRs decreased with NO
      elevating treatment and increased with NO-lowering treatment. Because ethanol,
      which is known to up-regulate mAChRs in SH-SY5Y cells, also decreased NO levels
      and because nNOS inhibition and ethanol effects on mAChRs were not additive, it
      is conceivable that ethanol-induced up-regulation of mAChRs involves inhibition
      of nNOS.

PMID- 11505041
TI  - Examination of a CYP2E1 repeat polymorphism in a monkey model of alcohol abuse.
AB  - BACKGROUND: Cytochrome P-450 2E1 (CYP2E1) is involved in alcohol metabolism, and
      the expression of this enzyme displays wide phenotypic variability in humans. It
      has been proposed that some of this variability in expression may be a
      consequence of the size of a repeat polymorphism in the 5" regulatory region of
      the gene and that the polymorphism may segregate with alcoholism. This study
      examined whether the repeat polymorphism exists in macaque monkeys and whether it
      associates with excessive alcohol consumption in this animal model. METHODS: Ten
      outbred cynomolgus monkeys (Macaca fascicularis) that displayed a voluntary
      alcohol consumption ranging from 1.0 to 3.6 g/kg/day were genotyped for a CYP2E1
      repeat polymorphism. This polymorphism has been documented in the region from 
      2519 base pair (bp) to -1953 bp of the human CYP2E1 gene 5" distal promoter.
      RESULTS: Individual polymerase chain reaction amplification of genomic DNA from
      each of the 10 monkey samples revealed a single band of approximately 400 bp in
      the region corresponding to the human CYP2E1 polymorphism. Polymerase chain
      reaction amplicons from the 10 individuals were sequenced, and each one generated
      a 370 bp sequence that is 90% identical to the human gene sequence. However,
      unlike human alleles that contain five to eight repeats, the cynomolgus monkey is
      homozygous for a single copy of the repeat most closely resembling repeat 8 (88%
      identical) in the human gene. CONCLUSIONS: These data demonstrate that the CYP2E1
      distal promoter region in monkeys is very similar to the human sequence yet lacks
      the extensive repeated DNA found in humans. This includes the rare repeats 3 and
      4, which have been postulated to play a role in transcription regulation and to
      associate with alcohol abuse liability in humans. These data suggest that the
      CYP2E1 polymorphism arose late in evolution and that the regulation of the gene
      by this genetic region is not associated with a heavy alcohol drinking phenotype
      in the cynomolgus monkey.

PMID- 11505042
TI  - The role of biomarkers in alcoholism medication trials.
AB  - BACKGROUND: Increasingly, biomarkers are being incorporated into the research
      design of clinical trials on medications to reduce drinking in alcoholics. To
      date, however, there has been little analysis of the unique roles that biomarkers
      can play in such investigations or of the practical and conceptual considerations
      that surround their best use in this context. METHODS: Clinical trials of
      alcoholism medications published between 1985 and the present were abstracted to
      determine how biomarkers were used and how changes in them related to self-report
      measures of drinking. RESULTS: Six uses of biomarkers were identified:
      determination of subjects to be included or excluded in the trial; description of
      baseline sample characteristics; primary and secondary outcome assessment;
      corroboration of self-reports of drinking status; specification of patients
      likely to respond to the medication; and evaluation of drug safety. CONCLUSION:
      Use of biomarkers in such studies appears warranted, particularly as an objective
      source of information on treatment efficacy that can be considered with patient
      self-report measures of drinking status. Biomarkers related to liver functioning
      also can assist in determination of drug safety for medications metabolized by
      the liver.

PMID- 11505043
TI  - Alterations in central preproenkephalin mRNA expression after chronic free-choice
      ethanol consumption by fawn-hooded rats.
AB  - BACKGROUND: Neurotransmission mediated via opioid and dopamine receptors is
      believed to be involved in the reinforcing and/or rewarding effects of ethanol
      consumption. We previously examined the effect of ethanol consumption (and
      naltrexone treatment, used clinically to treat alcoholism) on micro-opioid
      receptor density. We describe here the effect of free-choice ethanol consumption
      and naltrexone treatment on preproenkephalin, preprodynorphin, and dopamine D1
      and D2 receptor mRNA expression in the central nervous system. METHODS: Fawn
      hooded rats were given continual free-choice access to a 5% ethanol solution or
      water (4 weeks) followed by 2 weeks of water alone. At the end of this abstinence
      period, osmotic minipumps were implanted subcutaneously to deliver saline (n = 4)
      or naltrexone (n = 4; 8.4 mg/kg/day for 4 weeks). After recovery from surgery,
      the rats again were given access to 5% ethanol under the same free-choice
      conditions (4 weeks). A third group of age-matched controls drank only water
      during the behavioral trial. At the end of the behavioral trial, the rats were
      decapitated, and a quantitative examination of peptide precursor mRNAs was made
      by using in situ hybridization histochemistry. RESULTS: Naltrexone treatment
      significantly decreased preprodynorphin expression in the nucleus accumbens, but
      neither naltrexone treatment nor ethanol consumption significantly affected
      dopamine D1 and D2 receptor mRNA expression. In contrast, ethanol consumption
      increased preproenkephalin mRNA in the central and intercalated nuclei of the
      amygdala but decreased preproenkephalin mRNA in the nucleus accumbens and
      olfactory tubercle. The decreased level of preproenkephalin mRNA in the nucleus
      accumbens may reflect a neuroadaptive response to increased release of dopamine,
      whereas the increased level of preproenkephalin mRNA in the central nucleus of
      the amygdala may be associated with an anxiolytic effect of ethanol consumption.
      CONCLUSIONS: The data support the putative role of opioid peptides in the effects
      of ethanol and suggest that the nucleus accumbens and central nucleus of the
      amygdala are loci for the reinforcing effects of ethanol.

PMID- 11505044
TI  - Confirmation that offspring from families with alcohol-dependent individuals have
      greater hypothalamic-pituitary-adrenal axis activation induced by naloxone
      compared with offspring without a family history of alcohol dependence.
AB  - BACKGROUND: This study was designed to confirm our previous findings that
      nonalcoholic offspring from families with alcohol-dependent individuals have
      greater hypothalamic-pituitary-adrenal axis activation induced by opioid blockade
      compared with nonalcoholic subjects without a family history of alcohol
      dependence. METHODS: Sixty-four nonalcoholic subjects aged 18 to 25 years were
      enrolled in the protocol. Twenty-seven subjects were offspring from families with
      alcohol dependence and were designated as family history-positive subjects (FHP).
      Thirty-seven subjects were biological offspring of non-alcohol-dependent parents
      and were designated as family history-negative subjects (FHN). Subjects received
      naloxone hydrochloride (0, 50, 125, 375, and 500 microg/kg) in double-blind,
      randomized order; adrenocorticotropin (ACTH) and cortisol were monitored over 120
      min. RESULTS: No hormone differences at baseline or during placebo administration
      were identified between FHP and FHN subjects. FHP subjects had greater ACTH and
      cortisol response to opioid receptor blockade induced by naloxone hydrochloride
      compared with FHN subjects. CONCLUSIONS: These observations confirm previous
      findings that differences in ACTH and cortisol dynamics between FHP and FHN
      subjects can be unmasked by opioid receptor blockade.

PMID- 11505045
TI  - Effects of concurrent access to multiple ethanol concentrations and repeated
      deprivations on alcohol intake of alcohol-preferring rats.
AB  - BACKGROUND: The alcohol deprivation effect (ADE) is a temporary increase in the
      voluntary intake of ethanol solutions following a period of alcohol deprivation.
      Multiple deprivations can prolong the expression of an ADE. This study examined
      the effects of initial deprivation length, concurrent exposure to multiple
      ethanol concentrations, and number of deprivation exposures on the magnitude and
      duration of the ADE in alcohol-preferring (P) rats. METHODS: Adult female P rats
      received 24-hr free-choice access to 10, 20, and 30% ethanol and water for 6
      weeks. Rats were then randomly assigned to three groups; one group served as a
      nondeprived control, whereas the other two groups were initially deprived of
      ethanol for 2 or 8 weeks. The ethanol solutions were restored to both deprived
      groups for 2 weeks before the groups were deprived of ethanol for another 2
      weeks. This cycle was repeated three times for a total of four deprivations.
      RESULTS: After the initial ethanol deprivation period, both deprived groups
      displayed a similar 2-fold increased ethanol intake (g/Kg/day) during the initial
      24-hr period when ethanol was restored. Both deprived groups showed greater than
      2-fold increases in intake of the 20 and 30% ethanol solutions after re-exposure.
      Ethanol consumption returned to baseline levels within 2 weeks, before the
      subsequent deprivation period. Multiple deprivations increased the magnitude of
      the ADE over that observed in the first deprivation during the initial 24-hr
      period of re-exposure and prolonged the duration of the ADE. In addition,
      repeated deprivations increased ethanol intake in the first 2-hr period of re
      exposure and produced blood ethanol levels in excess of 150 mg/100 ml.
      CONCLUSIONS: Alterations in the reinforcing and/or aversive effects of alcohol
      occurred after a single prolonged deprivation and were enhanced with repeated
      deprivations.

PMID- 11505047
TI  - Origins and consequences of age at first drink. I. Associations with substance
      use disorders, disinhibitory behavior and psychopathology, and P3 amplitude.
AB  - BACKGROUND: Although an early age at first drink has been repeatedly associated
      with substantially elevated rates of alcoholism, the mechanisms underlying this
      association remain unclear. We investigated whether the association of age at
      first drink (AFD) with alcoholism was more consistent with the hypothesis that
      the former causes the latter or the hypothesis that both are manifestations of
      some common vulnerability. METHODS: We investigated whether substance use and
      mental health disorders, education, IQ, and personality were associated with AFD
      in a sample of 2670 adults; whether P3 amplitude was associated with AFD in a
      sample of 1127 17 year olds; and whether indicators of disinhibitory
      psychopathology assessed at age 11 predicted AFD by age 14 in a sample of 1343
      adolescents. RESULTS: In adults, AFD was associated not only with alcohol
      dependence, but also with a broad array of indicators of disinhibitory behavior
      and psychopathology including nicotine dependence, illicit drug abuse and
      dependence, conduct disorder, antisocial personality disorder, underachievement
      in school, and the personality trait of constraint. In 17 year olds, AFD was also
      associated with reduced P3 amplitude, a well-documented psychophysiological
      marker of alcoholism risk. Finally, in the early-adolescence sample, measures of
      behavioral disinhibition, including oppositionality, hyperactivity/impulsivity,
      and inattentiveness assessed at age 11 predicted drinking onset by age 14.
      CONCLUSIONS: Our findings indicated that AFD is not specifically associated with
      alcoholism but rather is correlated with a broad range of indicators of
      disinhibited behavior and psychopathology. Moreover, individuals who first drink
      at a relatively early age manifest elevated rates of disinhibitory behavior and
      psychopathology before they first try alcohol. Taken together, these findings
      suggest that the association of AFD with alcoholism reflects, at least in part, a
      common underlying vulnerability to disinhibitory behavior. Whether an early AFD
      directly influences risk of adult alcoholism remains unclear.

PMID- 11505046
TI  - Effect of tryptophan depletion on alcohol cue-induced craving in abstinent
      alcoholic patients.
AB  - BACKGROUND: The capacity of alcohol cues to precipitate the desire to drink may
      be an important determinant of relapse to alcohol use in recovering alcohol
      dependent patients. This study evaluated whether attenuation of serotonin
      synthesis via depletion of its precursor tryptophan reduces the magnitude of cue
      induced craving for alcohol in recently abstinent alcoholic individuals. METHODS:
      Alcohol-dependent patients (n = 16), 1 to 3 months after detoxification, who
      exhibited a 20% or greater increase in reported craving when presented with an
      alcoholic beverage, completed two additional alcohol cue-exposure test days, 1
      week apart. Each cue exposure was preceded by administration of a concentrated
      amino acid drink that resulted in a rapid and significant decline in plasma free
      tryptophan (active depletion, no tryptophan supplementation) or a similar drink
      containing tryptophan (placebo depletion). Tests were conducted in a randomized,
      double-blind fashion. RESULTS: There were no significant changes in the magnitude
      of cue-induced craving with active tryptophan depletion compared with placebo.
      CONCLUSIONS: These data question the dependence of alcohol cue-induced craving in
      sober alcoholics on the ongoing synthesis of serotonin.

PMID- 11505048
TI  - A comparison of substance use and injury among Mexican American emergency room
      patients in the United States and Mexicans in Mexico.
AB  - BACKGROUND: Emergency room (ER) studies have found differences in the association
      of alcohol with injury (intentional and unintentional) across cultures. These
      differences may be due to differences in drinking patterns across cultures. Few
      comparative data have been reported on associations of alcohol and injury between
      Mexican American ER patients and ER patients living in Mexico, and general
      population studies suggest that Mexican Americans may adopt more frequent heavy
      drinking patterns after migrating to the United States. METHODS: A comparative
      analysis of drinking, drug use, and injury was performed in probability samples
      of 550 ER patients from Santa Clara County (San Jose, CA) and 1417 ER patients in
      Pachuca (Hidalgo), Mexico. RESULTS: Both injured and uninjured (i.e., medical
      conditions) patients in Pachuca were less likely to report heavy drinking, drug
      use, drunkenness, or alcohol-related problems compared with those in Santa Clara.
      Those scoring high on level of acculturation in Santa Clara were more likely to
      report both drinking and drug use before the event, and heavy drinking, drug use,
      and consequences related to drinking in the last year compared with those scoring
      lower. Those scoring low on acculturation were similar on substance use variables
      to those in the Pachuca sample. CONCLUSIONS: Findings suggest that alcohol's
      association with injury may not just reflect typical drinking patterns in a
      culture. Among Mexican Americans, this association my vary by acculturation, and
      those migrating to the United States may be at increased risk for alcohol-related
      injury as their drinking patterns undergo change to those of the dominant
      culture. The ER, in this context, may take on increasing importance as a site for
      health services providers to implement intervention and prevention services for
      alcohol-related consequences in this ethnic group.

PMID- 11505049
TI  - The critical dimension of ethnicity in liver cirrhosis mortality statistics.
AB  - BACKGROUND: In 1997, liver cirrhosis was the 10th leading cause of death in the
      United States. Beginning in the 1950s, liver cirrhosis mortality rates have been
      consistently higher for black than for white men and women. There has been a
      gradual adoption of the recommendation that all death certificates include
      information on the Hispanic origin of decedents, with universal adoption in the
      1997 data year. It is the purpose of this study to examine the extent to which
      relative risks for cirrhosis mortality might shift for different demographic
      groups when Hispanic origin is considered along with the race and sex of the
      decedent. METHODS: Age-adjusted death rates were calculated for liver cirrhosis
      by using public-use data files produced by the National Center for Health
      Statistics. Trends in cirrhosis mortality rates from 1991 through 1997 are shown
      for white Hispanic, white non-Hispanic, black Hispanic, and black non-Hispanic
      men and women. RESULTS: In 1997, white Hispanic men show the highest cirrhosis
      mortality rates over the period examined, followed by black non-Hispanic and
      white non-Hispanic men, white Hispanic women, and black non-Hispanic and white
      non-Hispanic women. Among Hispanic decedents, the largest group was of Mexican
      ancestry, with large numbers being born outside the United States and having low
      education levels. CONCLUSIONS: The findings of higher risk for cirrhosis
      mortality among white men and women of Hispanic origin serve to focus new
      attention on these demographic groups. Collateral analyses of other causes of
      death do not support alternate explanations of these findings as artifacts of
      demographic misclassification. Future studies of amounts and patterns of alcohol
      consumption should include Hispanic origin among demographic factors examined.

PMID- 11505050
TI  - Interferon alpha and alcohol augment nuclear regulatory factor-kappaB activation
      in HepG2 cells, and interferon alpha increases pro-inflammatory cytokine
      production.
AB  - BACKGROUND: The mechanisms for decreased therapeutic response to IFNalpha in
      chronic hepatitis C patients with alcohol are unknown. We investigated the
      hypothesis that IFNalpha and alcohol regulate cells both in the liver parenchyma
      and the immune system. METHODS: We used the hepatocellular carcinoma cells
      (HepG2) to determine if IFNalpha (500-10,000 U/ml) or ethanol (25-100 mM)
      modulates NF-kB activation alone or in combination with TNFalpha (0.1-20
      microg/ml) as determined in electromobility gel shift assays. IkB levels were
      evaluated in the cytoplasmic extracts by western blot. Monocytes from normal
      donors were activated with LPS (1 microg/ml) in combination with IFNalpha or
      ethanol overnight and TNFalpha, IL-6, and IL-12 were measured in the
      supernatants. RESULTS: In HepG2 cells, both IFNalpha and acute alcohol treatment
      induced NF-kappaB activation and augmented TNFalpha-induced NF-kappaB binding.
      Pretreatment of HepG2 cells with IFNalpha resulted in the highest levels of NF
      kappaB activation in response to TNFalpha or TNFalpha plus ethanol stimulation.
      Supershift experiments confirmed that the NF-kappaB dimer induced by TNFalpha and
      its combination with IFNalpha or ethanol contains RelA (p65) and involves rapid
      degradation of IkappaBalpha. Experiments using the proteasome inhibitor, MG132,
      revealed that augmentation of NF-kappaB by ethanol and IFNalpha is mediated via
      the proteasome pathway. We show that in normal monocytes, IFNalpha augments LPS
      induced production of the inflammatory cytokines TNFalpha, IL-6, and IL-12 (p <
      0.06) without further modulation by acute alcohol treatment. CONCLUSIONS: These
      results suggest that IFNalpha can increase HepG2 cell sensitivity to TNFalpha and
      ethanol-mediated activation. Augmentation of monocyte inflammatory cytokines,
      particularly of IL-12 production, by IFNalpha could be a key element of the
      antiviral response in chronic HCV. These results support the hypothesis that the
      therapeutic benefits of IFNalpha likely involve activation of both immune and
      parenchymal cells in the liver.

PMID- 11505051
TI  - Increased serum IgE in alcoholics: relationship with Th1/Th2 cytokine production
      by stimulated blood mononuclear cells.
AB  - BACKGROUND: Increased serum immunoglobulin (Ig) E values are frequently found in
      alcoholics. Cytokines produced by T-helper-2 (Th2) lymphocytes are required for
      IgE synthesis. Chronic alcoholism is associated with altered cytokine balance.
      This study analyzed the relationship between Th1 and Th2 cytokine production by
      stimulated peripheral blood mononuclear cells (PBMCs) and serum IgE levels, both
      in atopic and nonatopic alcoholics. METHODS: Twenty-five patients admitted to the
      hospital with alcohol withdrawal syndrome were included in the study. Five were
      classified as atopic and 20 as nonatopic by means of skin-prick tests.
      Interleukin-4 (IL-4), IL-10, IL-12, IL-13, and interferon gamma were measured in
      the supernatants of 48-hr cultures of PBMCs stimulated with phytohemagglutinin.
      Total serum IgE was measured by chemiluminescent enzyme immunoassay. Results were
      compared with those of 15 healthy controls (seven atopics and eight nonatopics).
      RESULTS: Total serum IgE concentrations were higher in alcoholics than in
      controls, in both atopic and nonatopic subjects. The ratio of IL-4 to interferon
      gamma production by phytohemagglutinin-stimulated PBMCs (as an approach to
      Th2/Th1 balance) was significantly lower in alcoholics than in healthy controls,
      both in the atopic and in the nonatopic group. No difference was observed
      regarding IL-10, IL-12, and IL-13 production between alcoholics and controls. No
      correlation was demonstrated between cytokine production and total serum IgE
      levels in any group. CONCLUSIONS: Increased total serum IgE is observed in
      alcoholics together with a paradoxically low ratio of Th2 to Th1 cytokine
      production by phytohemagglutinin-stimulated PBMCs. These findings are independent
      of the atopic status of patients.

PMID- 11505052
TI  - Magnetic resonance relaxometry reveals central pontine abnormalities in
      clinically asymptomatic alcoholic men.
AB  - BACKGROUND: Central pontine myelinolysis (CPM) is a rare, debilitating, life
      threatening condition, associated with chronic alcoholism, rapid correction of
      hyponatremia, and advanced age. It is unknown, however, whether older alcoholic
      patients who by age and diagnosis are at risk for CPM have objectively determined
      neuroimaging evidence of preclinical CPM that could be valuable in understanding
      its development and in initiating appropriate treatment. Accordingly, we examined
      central pontine magnetic resonance (MR) transverse relaxation time (T2), which
      reflects myelin and axonal integrity when measured in white matter and is
      prolonged with pathology that causes increased free water content in tissue.
      METHODS: The subjects were 46 alcoholic men who were abstinent from alcohol for
      about 1 month and were asymptomatic for CPM, 9 men and 1 woman with alcoholic
      Korsakoff's syndrome (KS), and 74 healthy control men. All subjects received
      coronally acquired dual-echo MR imaging (MRI), from which T2 times were
      calculated in central pons. MRI films were read clinically and independently of
      relaxometry results. Hematological and neuropsychological data were also
      available for many subjects. RESULTS: Only the KS group showed prolonged T2
      times; however, pontine T2 prolongation increased significantly with older age in
      the asymptomatic alcoholics but not controls. Clinical radiological readings
      detected pontine signal hyperintensity in five KS subjects (two without dementia
      and three with dementia), one control, and no alcoholic patient. Hematologic
      indexes of macrocytic anemia and nutritional deficiency and neuropsychological
      measures of verbal and nonverbal fluency correlated with prolonged T2 times in
      alcoholic men. CONCLUSIONS: This CPM-like condition, manifest as prolonged T2,
      may occur with higher incidence than previously thought in clinically
      asymptomatic alcoholism and may contribute to neuropsychological compromise of
      initiation and production. Preclinical detection of abnormal pontine signal
      properties with MR relaxometry may identify patients at high risk for developing
      CPM.

PMID- 11505053
TI  - Effects of abstinence from alcohol on the broad phospholipid signal in human
      brain: an in vivo 31P magnetic resonance spectroscopy study.
AB  - BACKGROUND: In vivo phosphorus magnetic resonance spectroscopy (31P MRS) at a
      magnetic field strength of 1.5 T allows measurement of fairly mobile membrane
      phospholipids in the human brain. We previously showed that subjects who are
      heavy drinkers had a smaller signal and a shorter transverse relaxation time (T2)
      of white matter phospholipids than light drinkers, which suggested lower
      concentrations and molecular mobility of phospholipids in heavy drinkers. The
      purpose of the present study was to measure if such chronic alcohol-induced white
      matter tissue changes are persistent in long-term abstinent alcoholics. METHODS:
      Fourteen abstinent alcoholics (mean age 45 years, seven men and seven women) were
      studied by localized 31P MRS in the centrum semiovale and were compared with 13
      male, alcohol-dependent, heavy drinkers and 23 nondependent light drinkers (17
      men, 6 women) of similar age. Methods for measurements of the broad membrane
      phospholipid signal and its relaxation time were described previously. RESULTS:
      Phospholipid concentrations and relaxation times in alcoholics abstinent for an
      average of 31 months were not significantly different from those measured in
      light drinkers. The contribution of fast and slowly relaxing signal components to
      the broad phospholipid signal, however, was still different in abstinent
      alcoholics compared with light drinkers. No effects of sex or of family history
      of alcoholism were noted on any of our spectroscopic measures within the light
      drinking or abstinent groups. CONCLUSIONS: Most of our results suggest at least
      partial recovery of chronic alcohol-induced white matter phospholipid damage with
      long-term abstinence. They offer myelination changes and/or dendritic
      rearborization as a possible mechanism for the commonly observed white matter
      volume gain with prolonged abstinence. But the results also suggest a persistent
      abnormality in the nature and/or physical properties of white matter
      phospholipids in long-term abstinent alcoholics.

PMID- 11505054
TI  - Early alteration in leukocyte populations and Th1/Th2 function in ethanol
      consuming mice.
AB  - BACKGROUND: Chronic alcohol consumption polarizes the immune response away from
      Th1-mediated cell-mediated immunity. In the present report we investigate the
      first onset of alteration in immune parameters during ethanol consumption in
      terms of changes in splenic leukocyte cellularity and surface phenotype as well
      as alterations in Th1 and Th2 function. METHODS: BALB/c and C57BL/6 mice were fed
      ethanol-containing liquid diets, were pair-fed an isocaloric liquid control diet,
      or were fed solid diet and water ad libitum for up to 12 days. At intervals
      during the feeding period, splenic leukocytes were assessed for phenotypic
      markers by flow cytometry and for their ability to support antigen-induced
      interferon-gamma (IFNgamma) production in a coculture system. Mice were bled at
      intervals throughout the feeding period, and serum immunoglobin E (IgE) and
      alcohol levels were determined. RESULTS: Data show that phenotypic and functional
      alterations occur within the first few days of alcohol consumption. Both liquid
      diets affect splenic cellularity, and by dietary day 5, ethanol-containing liquid
      diets further reduce B and NK cell numbers. The decline in B cells is accompanied
      by a concomitant decline in the amount of major histocompatibility complex class
      II expressed on this population. Functional alteration in Th1-mediated IFNgamma
      production occurred in the population fed ethanol-containing liquid diets by
      dietary day 5. Th2 function, as indicated by systemic serum IgE levels in these
      unimmunized mice, is increased by dietary day 6 to 8 and correlated with
      significant blood alcohol levels. CONCLUSIONS: Ethanol consumption by mice causes
      a rapid decrease in splenic cellularity accompanied by a decrease in Th1 function
      and a rapid increase in systemic IgE levels.

PMID- 11505055
TI  - Effect of ethanol on polyunsaturated fatty acid biosynthesis in hepatocytes from
      spontaneously hypertensive rats.
AB  - BACKGROUND: Polyunsaturated fatty acids (PUFA) play a major role in membrane
      structures that are modified during alcoholism. PUFA are also precursors of
      second messengers-eicosanoids-involved in the regulation of blood pressure.
      Alcohol has been related to hypertension and to alterations in liver PUFA
      metabolism. We investigated the effects of ethanol on PUFA biogenesis in
      hepatocytes of Wistar Kyoto (WKY) rats and Spontaneously Hypertensive Rats (SHR).
      The effects of a diet enriched with n-3 PUFA, which is known to modulate
      hypertension, were also studied. METHODS: Isolated hepatocytes from male
      normotensive Wistar Kyoto (WKY) rats and SHR were incubated for 60 min in the
      presence of labeled linoleic acid and DGLA, which are precursors of the limiting
      desaturation steps of PUFA biosynthesis, into a medium containing different
      concentrations of ethanol. Hepatocytes from SHR that were fed a diet supplemented
      with n-3 PUFA were incubated with the same precursors. RESULTS: First, the
      hepatic biogenesis of PUFA is dependent on the level of ethanol in the incubation
      medium. Second, Delta5 desaturase was more sensitive than Delta6 desaturase to
      changes in alcohol concentration. Third, in SHR, a tremendous decrease of
      arachidonic acid biosynthesis was evidenced in alcohol-intoxicated hepatocytes;
      the effect was reinforced when ethanol concentration was high, mainly for Delta5
      desaturase. Fourth, in the presence of ethanol, the biogenesis of PUFA was
      altered in isolated hepatocytes from SHR that were fed the diet supplemented with
      n-3 PUFA, particularly via an inhibition of Delta5 desaturation. CONCLUSIONS: Our
      study showed that hepatocyte PUFA biogenesis is dependent on ethanol
      concentration. Ethanol strongly inhibits the synthesis of PUFA in hepatocytes
      from SHR, which can explain the deficit of prostaglandin precursors observed in
      cardiovascular diseases linked to ethanol intoxication. n-3 PUFA supplemented
      diet reinforces the inhibition of arachidonic acid synthesis, likely by a
      substrate competition toward Delta5 desaturation. This in vitro approach provides
      a better understanding of the effects of ethanol on fatty acid metabolism in
      relation to hypertension.

PMID- 11505056
TI  - Timing of moderate alcohol exposure during pregnancy and neonatal outcome in
      rhesus monkeys (Macaca mulatta).
AB  - BACKGROUND: Moderate prenatal alcohol exposure can contribute to
      neurodevelopmental deficits in nonhuman primate offspring. The purpose of this
      study was to examine the effects of gestational timing of alcohol exposure on
      neurobehavior with a nonhuman primate model. METHODS: Sixty-three rhesus monkey
      infants (Macaca mulatta), from four groups of females, were assessed: (1) an
      early alcohol-exposed group, in which mothers voluntarily consumed alcohol on
      gestational days 0 through 50; (2) a mid to late gestation alcohol-exposed group,
      in which mothers consumed an identical dose on gestation days 50 through 135; (3)
      a continuous-exposure group, in which mothers consumed an identical dose on days
      0 through 135 or days 0 through 165; and (4) controls, in which mothers
      voluntarily consumed an isocaloric control solution on gestational days 0 through
      50, 50 through 135, 0 through 135, or 0 through 165. Data were obtained on
      offspring for measures of growth and neurobehavior. RESULTS: There were no
      effects of alcohol on birthweight, gestation length, or ponderal index. Prenatal
      exposure to alcohol during early gestation significantly decreased scores on
      infant neurobehavioral tests overall in multivariate tests, after controlling for
      birthweight. Univariate tests showed that early gestation alcohol exposure was
      related to reductions in infant orientation and motor maturity. Mid- to late
      gestation exposure also resulted in a reduction in motor maturity but did not
      affect overall neurobehavioral performance in the multivariate tests.
      CONCLUSIONS: Early-gestation alcohol exposure is as deleterious to neonatal
      neurobehavior as late-gestation or continuous exposure. Moreover, neurobehavior
      seems to be a more sensitive marker of early-gestation moderate alcohol exposure
      than growth parameters. Women who are attempting to become pregnant should
      minimize frequent social drinking, because subtle neurodevelopmental effects to
      the fetus may be induced before pregnancy is detected.

PMID- 11505058
TI  - Impact of delayed gastric emptying on the outcome of antireflux surgery.
AB  - OBJECTIVE: To study the effect of Nissen fundoplication on the pattern of gastric
      emptying and intragastric distribution of symptoms in patients with normal and
      delayed gastric emptying before surgery, especially in those with delayed
      emptying before surgery. SUMMARY BACKGROUND DATA: Gastroesophageal reflux disease
      is associated with delayed gastric emptying and dyspeptic symptoms in
      approximately 40% of the patients. After Nissen fundoplication, dyspeptic
      symptoms are also not uncommon. METHODS: Thirty-six patients (26 men, 10 women,
      mean age 43.1) were studied before and 3 months after Nissen fundoplication.
      Gastric emptying (dual-isotope, expressed in lag phase, emptying rate, T50, and
      intragastric distribution) was not included in the decision for surgery. Reflux
      related and dyspeptic symptoms were scored before and at 3, 6, and 12 months
      after surgery. RESULTS: Twenty-six patients had normal and 10 had delayed gastric
      emptying before surgery. Nissen fundoplication on average enhanced gastric
      emptying for solids in both subgroups by a combination of a decrease in mean lag
      phase, emptying rate, and T50. The preoperative difference in intragastric
      distribution between patients with and without delayed gastric emptying was
      abolished by fundoplication. Patients with normal gastric emptying before surgery
      showed an increase in early postprandial satiety; in those with delayed emptying,
      this was not observed. A correlation was found between preoperative T50 for
      liquid gastric emptying and postoperative nausea at 3 months in patients with
      normal gastric emptying. In patients with delayed emptying, preoperative
      correlations between lag phase for liquids and nausea respectively early satiety
      were significant, as well as for T50 for liquids and vomiting. CONCLUSIONS:
      Nissen fundoplication equalizes the preoperative difference in intragastric
      distribution and accelerates gastric emptying without an effect on symptoms in
      patients with preexisting delayed gastric emptying, but with an increase in early
      satiety in patients with normal gastric emptying. Delayed gastric emptying is not
      a contraindication for antireflux surgery.

PMID- 11505059
TI  - Delayed gastric emptying in patients with abnormal gastroesophageal reflux.

PMID- 11505060
TI  - 2,500 living donor kidney transplants: a single-center experience.
AB  - OBJECTIVE: To review a single center's experience and outcome with living donor
      transplants. SUMMARY BACKGROUND DATA: Outcome after living donor transplants is
      better than after cadaver donor transplants. Since the inception of the authors'
      program, they have performed 2,540 living donor transplants. For the most recent
      cohort of recipients, improvements in patient care and immunosuppressive
      protocols have improved outcome. In this review, the authors analyzed outcome in
      relation to protocol. METHODS: The authors studied patient and graft survival by
      decade. For those transplanted in the 1990s, the impact of immunosuppressive
      protocol, donor source, diabetes, and preemptive transplantation was analyzed.
      The incidence of rejection, posttransplant steroid-related complications, and
      return to work was determined. Finally, multivariate analysis was used to study
      risk factors for worse 1-year graft survival and, for those with graft function
      at 1 year, to study risk factors for worse long-term survival. RESULTS: For each
      decade since 1960, outcome has improved after living donor transplants. Compared
      with patients transplanted in the 1960s, those transplanted in the 1990s have
      better 8-year actuarial patient and graft survival rates. Death with function and
      chronic rejection have continued to be a major cause of graft loss, whereas acute
      rejection has become a rare cause of graft loss. Cardiovascular deaths have
      become a more predominant cause of patient death; infection has decreased. Donor
      source (e.g., ideally HLA-identical sibling) continues to be important. For
      living donor transplants, rejection and graft survival rates are related to donor
      source. The authors show that patients who had preemptive transplants or less
      than 1 year of dialysis have better 5-year graft survival and more frequently
      return to full-time employment. Readmission and complications remain problems; of
      patients transplanted in the 1990s, only 36% never required readmission.
      Similarly, steroid-related complications remain common. The authors' multivariate
      analysis shows that the major risk factor for worse 1-year graft survival was
      delayed graft function. For recipients with 1-year graft survival, risk factors
      for worse long-term outcome were pretransplant smoking, pretransplant peripheral
      vascular disease, pretransplant dialysis for more than 1 year, one or more acute
      rejection episodes, and donor age older than 55. CONCLUSIONS: These data show
      that the outcome of living donor transplants has continued to improve. However,
      for living donors, donor source affects outcome. The authors also identify other
      major risk factors affecting both short- and long-term outcome.

PMID- 11505061
TI  - Real-time Internet connections: implications for surgical decision making in
      laparoscopy.
AB  - OBJECTIVE: To determine whether a low-bandwidth Internet connection can provide
      adequate image quality to support remote real-time surgical consultation. SUMMARY
      BACKGROUND DATA: Telemedicine has been used to support care at a distance through
      the use of expensive equipment and broadband communication links. In the past,
      the operating room has been an isolated environment that has been relatively
      inaccessible for real-time consultation. Recent technological advances have
      permitted videoconferencing over low-bandwidth, inexpensive Internet connections.
      If these connections are shown to provide adequate video quality for surgical
      applications, low-bandwidth telemedicine will open the operating room environment
      to remote real-time surgical consultation. METHODS: Surgeons performing a
      laparoscopic cholecystectomy in Ecuador or the Dominican Republic shared real
      time laparoscopic images with a panel of surgeons at the parent university
      through a dial-up Internet account. The connection permitted video and audio
      teleconferencing to support real-time consultation as well as the transmission of
      real-time images and store-and-forward images for observation by the consultant
      panel. A total of six live consultations were analyzed. In addition, paired local
      and remote images were "grabbed" from the video feed during these laparoscopic
      cholecystectomies. Nine of these paired images were then placed into a Web-based
      tool designed to evaluate the effect of transmission on image quality. RESULTS:
      The authors showed for the first time the ability to identify critical anatomic
      structures in laparoscopy over a low-bandwidth connection via the Internet. The
      consultant panel of surgeons correctly remotely identified biliary and arterial
      anatomy during six laparoscopic cholecystectomies. Within the Web-based
      questionnaire, 15 surgeons could not blindly distinguish the quality of local and
      remote laparoscopic images. CONCLUSIONS: Low-bandwidth, Internet-based
      telemedicine is inexpensive, effective, and almost ubiquitous. Use of these
      inexpensive, portable technologies will allow sharing of surgical procedures and
      decisions regardless of location. Internet telemedicine consistently supported
      real-time intraoperative consultation in laparoscopic surgery. The implications
      are broad with respect to quality improvement and diffusion of knowledge as well
      as for basic consultation.

PMID- 11505062
TI  - Proliferative activity in Barrett's esophagus before and after antireflux
      surgery.
AB  - OBJECTIVE: To assess proliferation in the columnar-lined esophageal mucosa before
      and after antireflux surgery. SUMMARY BACKGROUND DATA: Intestinal metaplasia
      persists in Barrett's mucosa after reflux control. It remains at risk for
      uncontrolled cellular proliferation and adenocarcinoma formation. METHODS: Forty
      five patients with Barrett's esophagus had a mean follow-up of 4 years after a
      Collis-Nissen gastroplasty. Proliferative activity was assayed
      immunohistochemically for Ki-67 expression in 73 preoperative and 176
      postoperative biopsies. Correlation with manometric and 24-hour pH results was
      obtained. RESULTS: The Collis-Nissen gastroplasty restored the median lower
      esophageal sphincter gradient from 5.5 mmHg before surgery to 14.5 mmHg at 24
      months and 12.9 mmHg at 48 months after surgery. The median esophageal acid
      exposure was reduced from 8% to 1% and 1% of recording time, respectively. The
      median Ki-67 labeling index increased from 28.5% before surgery to 36.1% at 12 to
      23 months. It returned to preoperative level (26.9%) at 24 to 47 months. After
      surgery, abnormal intraesophageal acid exposure was documented in 12 patients but
      could not be correlated with sphincter pressure. After surgery, the pattern of
      proliferation in patients with acid exposure less than 4% in their esophagus
      showed significant differences when compared with the proliferation pattern of
      patients where abnormal intraesophageal acid exposure was recorded. New present
      dysplasia was observed only in patients with abnormal acid exposure. CONCLUSIONS:
      In Barrett's mucosa, from preoperative values, proliferation peaked early after
      surgery and then decreased to preoperative levels. Despite sphincter restoration
      and global reflux control, abnormal esophageal acid exposure persisted in 12
      patients. Patients with abnormal esophageal acid exposure displayed more
      proliferation and more dysplasia.

PMID- 11505063
TI  - Risk factors for surgical site infection after elective resection of the colon
      and rectum: a single-center prospective study of 2,809 consecutive patients.
AB  - OBJECTIVE: To identify the risk factors for surgical site infection (SSI) in
      patients undergoing elective resection of the colon and rectum. SUMMARY
      BACKGROUND DATA: SSI causes a substantial number of deaths and complications.
      Determining risk factors for SSI may provide information on reducing
      complications and improving outcome. METHODS: The authors performed a prospective
      study of 2,809 consecutive patients undergoing elective colorectal resection via
      laparotomy between February 1995 and December 1998 at a single institution. The
      outcome of interest was SSI, which was classified as being incisional or
      organ/space with or without clinical leakage. A likelihood ratio forward
      regression model was used to assess the independent association of variables with
      SSIs. RESULTS: The overall SSI, incisional SSI, and organ/space SSI with and
      without clinical anastomotic leakage rates were 4.7%, 3%, 2%, and 0.8%,
      respectively. Risk factors for overall SSI were American Society of
      Anesthesiology (ASA) score 2 or 3 (odd ratio [OR] = 1.7), male gender (OR = 1.5),
      surgeons (OR = 1.3-3.3), types of operation (OR = 0.3-2.1), creation of ostomy
      (OR = 2.1), contaminated wound (OR = 2.9), use of drainage (OR = 1.6), and intra-
      or postoperative blood transfusion (1-3 units, OR = 5.3; >/=4 units, OR = 6.2).
      However, SSIs at specific sites differed from each other with respect to the risk
      factors. Among a variety of risk factors, only blood transfusion was consistently
      associated with a risk of SSI at any specific site. CONCLUSIONS: In addition to
      ASA score and surgical wound class, blood transfusion, creation of ostomy, types
      of operation, use of drainage, sex, and surgeons were important in predicting
      SSIs after elective colorectal resection.

PMID- 11505064
TI  - Prognostic determinants of patients with lateral nodal involvement by rectal
      cancer.
AB  - OBJECTIVE: To clarify the characteristics related to long-term survival in
      patients with lateral nodal involvement. SUMMARY BACKGROUND DATA: Few reports
      have addressed the prognostic determinants in patients with actual lateral nodal
      involvement, which are important in determining treatment. METHODS: Review of a
      prospective colorectal database at a single institution for a 10-year period
      (1987-1996) identified 53 patients with lateral nodal involvement. RESULTS: All
      nine patients who underwent resection of synchronous distant metastases developed
      recurrence and died within 3 years. Of the 44 patients without distant
      metastases, 25 (57%) developed locoregional recurrence, and the overall 5-year
      survival rate was 32%. Multivariate analysis showed that age, total number of
      involved nodes (mesorectal and lateral), and circumferential surgical margin
      involvement had independently predicted postoperative survival. Patients with
      three or fewer nodes involved accounted for one third of lateral-positive
      patients, with a 5-year survival rate of 75%, whereas the 18 patients with four
      or more involved nodes had a 5-year survival rate of 4%. All eight patients with
      circumferential margin involvement died of carcinoma, and seven developed
      locoregional recurrences. Involvement of other pelvic organs had no effect on
      prognosis, nor were adverse prognostic outcomes noted by the region of lateral
      involvement. CONCLUSIONS: For patients with lateral involvement, the most
      important prognostic variables are distant metastases, the total number of nodes
      involved, circumferential margin involvement, and age. Selection of patients
      based on these variables may lead to the identification of a subgroup for whom
      lateral nodal dissection could be the first treatment choice.

PMID- 11505065
TI  - Second-look surgery in patients with peritoneal dissemination from appendiceal
      malignancy: analysis of prognostic factors in 98 patients.
AB  - OBJECTIVE: To establish selection criteria for reoperation in patients with
      peritoneal dissemination from appendiceal malignancy. SUMMARY BACKGROUND DATA:
      The outcome of patients with mucinous appendiceal neoplasms with peritoneal
      surface dissemination has changed as a result of a better understanding of the
      clinical and pathologic features of this disease. This knowledge, combined with
      aggressive strategies for the use of perioperative intraperitoneal chemotherapy
      and peritonectomy procedures, has resulted in long-term disease-free survival in
      many of these patients. However, some of the patients develop progressive
      disease, and a question regarding additional surgery is appropriate. A critical
      analysis of the results of second-look surgery should assist in the management of
      patients with recurrent peritoneal surface dissemination of an appendiceal
      neoplasm. METHODS: Three hundred twenty-one patients with epithelial peritoneal
      surface malignancy of appendiceal origin underwent surgery during a 12-year
      period. Ninety-eight of these patients (30.5%) underwent a second-look procedure.
      A database of selected clinical features regarding these 98 patients was gathered
      from the clinical records. A critical statistical analysis of these clinical
      features and their prognostic impact was performed using survival as an endpoint.
      All patients were managed by a treatment regimen that used cytoreductive surgery
      and intraperitoneal chemotherapy. RESULTS: The overall 5-year survival rate of
      these 98 patients was 73.6%. This compared favorably with a 68% survival rate of
      223 patients who did not undergo reoperation. Survival based on the number of
      cytoreductive surgeries and the free interval between them showed no significant
      difference. Patients who had second-look surgery with bowel obstruction as a
      symptom and those in whom the amount of tumor was increased or minimally
      decreased at the first and second cytoreductions had a significantly inferior 5
      year survival rate. A complete second cytoreduction was associated with an
      improved 5-year survival rate. CONCLUSIONS: Follow-up of patients treated for
      peritoneal dissemination from neoplasms of appendiceal origin is indicated.
      Selected patients in whom recurrence develops are candidates for repeat
      cytoreductive surgery plus intraperitoneal chemotherapy with curative intent.

PMID- 11505066
TI  - Resection of hepatocellular carcinoma without preoperative tumor biopsy.
AB  - OBJECTIVE: To evaluate the need for a preoperative tumor biopsy of liver lesions
      suspicious for hepatocellular carcinoma (HCC). SUMMARY BACKGROUND DATA: With
      advances in liver imaging, the results of recent studies have suggested a very
      high accuracy of preoperative evaluation of liver masses suspicious of HCC,
      making preoperative tumor biopsy unnecessary. METHODS: A retrospective analysis
      was conducted of all liver resections for HCC at the Toronto General and Mt.
      Sinai Hospitals, Toronto, between October 1994 and December 1998. RESULTS: Sixty
      patients underwent 65 liver resections without a preoperative liver biopsy. The
      median age was 61 years. Sixty percent of the patients had cirrhosis and 38.5%
      had noncirrhotic chronic hepatitis. HCC was confirmed histologically in the
      surgical specimen in 63 of the 65 cases (96.9%). Both patients without HCC had a
      significant risk factor for HCC (chronic hepatitis C and alcohol in one and
      chronic hepatitis B and previous resection for HCC in the other). The lesions
      were 2 cm and 2.7 cm in diameter, and the alpha-fetoprotein level was low (<5 and
      22 ng/mL, respectively). In such patients, with tumor 3 cm or smaller and an
      alpha-fetoprotein level less than 100 ng/mL (10 patients), the false-positive
      rate for the preoperative diagnosis was 2/10 (20%). CONCLUSIONS: Preoperative
      diagnosis of HCC was highly accurate in lesions larger than 3 cm. Tumor biopsy is
      unnecessary in these patients. However, in a subgroup of patients with lesions
      less than 3 cm, particularly those with alpha-fetoprotein levels less than 100
      ng/mL, there is a higher false-positive diagnostic rate, and tumor biopsy should
      be considered.

PMID- 11505067
TI  - Late development of bile duct cancer in patients who had biliary-enteric drainage
      for benign disease: a follow-up study of more than 1,000 patients.
AB  - OBJECTIVE: To evaluate the correlation between biliary-enteric surgical drainage
      and the late development of cholangiocarcinoma of the biliary tract. SUMMARY
      BACKGROUND DATA: In patients with biliary-enteric drainage, reflux of intestinal
      contents into the bile duct may occur and cause cholangitis, which is regarded as
      the most serious complication of these procedures. Lithiasis of the biliary tract
      and a previous biliary-enteric anastomosis have both been suggested to favor the
      late onset of cholangiocarcinoma. METHODS: Consecutive patients (n = 1,003)
      undergoing three different procedures of biliary-enteric anastomosis
      (transduodenal sphincteroplasty, choledochoduodenostomy, and hepaticojejunostomy)
      between 1967 and 1997 were included in this study. The postoperative clinical
      course and long-term outcome were evaluated by a retrospective review of the
      hospital records and follow-up. Mean follow-up was 129.6 months. RESULTS: Fifty
      five (5.5%) cases of primary bile duct cancer were found among the 1,003 patients
      at intervals of 132 to 218 months from biliary-enteric anastomosis. The incidence
      of cholangiocarcinoma in the three groups was 5.8% in transduodenal
      sphincteroplasty patients, 7.6% in choledochoduodenostomy patients, and 1.9% in
      hepaticojejunostomy patients. The incidence of malignancy related to the
      different underlying diagnosis was 5.9%, 7.2%, and 1.9% in patients with
      choledocholithiasis, sphincter of Oddi stenosis, and postoperative benign
      stricture, respectively. Although only one patient who developed
      cholangiocarcinoma had previous concurrent lithiasis of the biliary tract, 40
      patients had experienced mostly severe, recurrent cholangitis. No case of
      malignancy occurred in patients scored as having no cholangitis in the early and
      long-term postoperative outcome. Univariate and multivariate analyses have shown
      the presence of cholangitis as the only factor affecting the incidence of
      cholangiocarcinoma. CONCLUSIONS: Chronic inflammatory changes consequent to
      biliary-enteric drainage should be closely monitored for the late development of
      biliary tract malignancies.

PMID- 11505068
TI  - Response to chemotherapy and predictors of survival in adult rhabdomyosarcoma.
AB  - OBJECTIVE: To assess outcome and identify predictors of survival of adults with
      rhabdomyosarcoma. SUMMARY BACKGROUND DATA: The literature on adult
      rhabdomyosarcoma is limited. Few studies have identified predictors of long-term
      survival in this patient population. METHODS: Thirty-nine adults with
      rhabdomyosarcoma were treated between 1973 and 1996 and prospectively followed.
      Outcomes were assessed with respect to patient and tumor characteristics, local
      treatment, and response to chemotherapy. RESULTS: Twenty-six patients had
      localized/locoregional disease and 13 patients had metastatic disease at
      presentation. Twenty-one patients underwent attempted curative resection, 27
      received radiotherapy, and 37 received chemotherapy. Median follow-up for
      surviving patients was 152 months. The overall 5- and 10-year survival rates were
      31% and 27%, respectively. Five-year survival rates for patients with tumors less
      than 5 cm, 5 to 10 cm, and more than 10 cm were 60%, 14%, and 0%, respectively.
      Patients with localized/locoregional disease at presentation had a 44% 5-year
      survival rate; there were no 5-year survivors among patients with metastatic
      disease. Patients who had a complete response to chemotherapy had a 5-year
      survival rate of 57%, compared with a rate of only 7% for poor responders.
      Metastatic disease at presentation and poor response to chemotherapy were
      independent predictors of death on multivariate analysis. CONCLUSIONS: Age,
      location, nodal status, and histologic subtype do not appear be associated with
      survival in adults with rhabdomyosarcoma treated with multimodal therapy.
      Metastatic disease at presentation and poor response to chemotherapy are strongly
      associated with poor prognosis. Future systemic therapies should be targeted to
      patients with localized/locoregional disease and partial responders to
      conventional chemotherapy.

PMID- 11505069
TI  - Trauma inhibits erythroid burst-forming unit and granulocyte-monocyte colony
      forming unit growth through the production of TGF-beta1 by bone marrow stroma.
AB  - OBJECTIVE: To examine the effect of trauma plasma on clonogenic progenitor
      cultures. SUMMARY BACKGROUND DATA: Severely injured trauma patients often
      experience altered hematopoietic functions, manifested by an increased
      susceptibility to infection and the development of a persistent anemia.
      Experimental and clinical data suggest that trauma results in the release of
      cytokines into the plasma that have hematopoietic regulatory function, but few
      studies have examined human bone marrow. METHODS: Plasma was obtained from 42
      severely injured patients admitted to the surgical intensive care unit from days
      1 to 15 after injury. Bone marrow and normal plasma were obtained from
      volunteers. Bone marrow mononuclear cells were isolated and plated for
      granulocyte-monocyte colony-forming unit (CFU-GM) and erythroid burst-forming
      unit (BFU-E) growth. Parallel cultures were incubated with 2% (v/v) trauma or
      normal plasma. Additional cultures were plated with neutralizing concentrations
      of antibodies to transforming growth factor (TGF)-beta1 and MIP-1alpha.
      Circulating plasma TGF-beta1 was determined by bioassay. mRNA from bone marrow
      stromal cultures was extracted and probed for TGF-beta1 and macrophage
      inflammatory protein (MIP)-1alpha. RESULTS: Trauma plasma suppressed CFU-GM and
      BFU-E colony growth by 40% to 60% at all time periods after injury compared with
      cultures incubated with normal plasma. Using a noncontact culture system, the
      authors showed that this inhibition of BFU-E and CFU-GM colony growth was
      mediated by bone marrow stroma. The inhibition appeared to be due to soluble
      plasma-induced bone marrow stromal products that did not require direct cell-cell
      contact. The addition of anti-TGF-beta1 antibodies reversed the suppressive
      effect of trauma plasma on CFU-GM and BFU-E colony growth during the early but
      not late time points after injury. Trauma but not normal plasma induced TGF-beta1
      mRNA in bone marrow stroma. CONCLUSIONS: Trauma plasma inhibits bone marrow BFU-E
      and CFU-GM colony growth for up to 2 weeks after injury. This inhibition is
      mediated through the interaction of trauma plasma with bone marrow stroma. TGF
      beta1 production by bone marrow stroma appears to plays an important role in the
      early but not late bone marrow suppression after injury.

PMID- 11505070
TI  - Bactericidal/permeability-increasing protein attenuates systemic inflammation and
      acute lung injury in porcine lower limb ischemia-reperfusion injury.
AB  - OBJECTIVE: To investigate the role of recombinant bactericidal/permeability
      increasing protein (rBPI21) in the attenuation of the sepsis syndrome and acute
      lung injury associated with lower limb ischemia-reperfusion (I/R) injury. SUMMARY
      BACKGROUND DATA: Gut-derived endotoxin has been implicated in the conversion of
      the sterile inflammatory response to a lethal sepsis syndrome after lower torso
      I/R injury. rBPI21 is a novel antiendotoxin therapy with proven benefit in
      sepsis. METHODS: Anesthetized ventilated swine underwent midline laparotomy and
      bilateral external iliac artery occlusion for 2 hours followed by 2.5 hours of
      reperfusion. Two groups (n = 6 per group) were randomized to receive, by
      intravenous infusion over 30 minutes, at the start of reperfusion, either
      thaumatin, a control-protein preparation, at 2 mg/kg body weight, or rBPI21 at 2
      mg/kg body weight. A control group (n = 6) underwent laparotomy without further
      treatment and was administered thaumatin at 2 mg/kg body weight after 2 hours of
      anesthesia. Blood from a carotid artery cannula was taken every half-hour for
      arterial blood gas analysis. Plasma was separated and stored at -70 degrees C for
      later determination of plasma tumor necrosis factor (TNF)-alpha, interleukin (IL)
      6 by bioassay, and IL-8 by enzyme-linked immunosorbent assay (ELISA), as a
      markers of systemic inflammation. Plasma endotoxin concentration was measured
      using ELISA. Lung tissue wet-to-dry weight ratio and myeloperoxidase
      concentration were used as markers of edema and neutrophil sequestration,
      respectively. Bronchoalveolar lavage protein concentration was measured by the
      bicinclinoic acid method as a measure of capillary-alveolar protein leak. The
      alveolar-arterial gradient was measured; a large gradient indicated impaired
      oxygen transport and hence lung injury. RESULTS: Bilateral hind limb I/R injury
      increased significantly intestinal mucosal acidosis, intestinal permeability,
      portal endotoxemia, plasma IL-6 concentrations, circulating phagocytic cell
      priming and pulmonary leukosequestration, edema, capillary-alveolar protein leak,
      and impaired gas exchange. Conversely, pigs treated with rBPI21 2 mg/kg at the
      onset of reperfusion had significantly reduced intestinal mucosal acidosis,
      portal endotoxin concentrations, and circulating phagocytic cell priming and had
      significantly less pulmonary edema, leukosequestration, and respiratory failure.
      CONCLUSIONS: Endotoxin transmigration across a hyperpermeable gut barrier,
      phagocytic cell priming, and cytokinemia are key events of I/R injury, sepsis,
      and pulmonary dysfunction. This study shows that rBPI21 ameliorates these adverse
      effects and may provide a novel therapeutic approach for prevention of I/R
      associated sepsis syndrome.

PMID- 11505071
TI  - Sequential changes in the metabolic response to orthotopic liver transplantation
      during the first year after surgery.
AB  - OBJECTIVE: To quantify the sequential changes in the metabolic response occurring
      in patients with end-stage liver disease after orthotopic liver transplantation
      (OLT). SUMMARY BACKGROUND DATA: Detailed quantification of the changes in energy
      expenditure, body composition, and physiologic function that occur in patients
      after OLT has not been performed. Understanding these changes is essential for
      the optimal management of these patients. METHODS: Fourteen patients who
      underwent OLT for end-stage liver disease had measurements of resting energy
      expenditure, body composition, and physiologic function immediately before
      surgery and 5, 10, 15, 30, 90, 180, and 360 days later. RESULTS: Resting energy
      expenditure was significantly elevated after surgery (24% above predicted),
      peaking around day 10 after OLT, when it averaged 42% above predicted. A
      significant degree of hypermetabolism was still present at 6 months, but at 12
      months measured resting energy expenditure was close to predicted values. Before
      surgery, measured total body protein was 82% of estimated preillness total body
      protein. During the first 10 days after OLT, a further 1.0 kg (10%) of total body
      protein was lost, mostly from skeletal muscle. Only 54% of this loss was restored
      by 12 months. Significant overhydration of the fat-free body was seen before OLT,
      and it was still present 12 months later. Although significant losses of body fat
      and bone mineral occurred during the early postoperative period, only body fat
      stores were restored at 12 months. Both subjective fatigue score and voluntary
      hand grip strength improved rapidly after OLT to exceed preoperative levels at 3
      months. At 12 months grip strength was close to values predicted for these
      patients when well. Respiratory muscle strength improved less markedly and was
      significantly lower than predicted normal levels at 12 months. CONCLUSIONS:
      Before surgery, these patients were significantly protein-depleted, overhydrated,
      and hypermetabolic. After surgery, the period of hypermetabolism was prolonged,
      restoration of body protein stores was gradual and incomplete, and respiratory
      muscle strength failed to reach expected normal values. Our measurements indicate
      that OLT does not normalize body composition and function and imply that a
      continuing metabolic stress persists for at least 12 months after surgery.

PMID- 11505073
TI  - Does prophylactic octreotide decrease the rates of pancreatic fistula and other
      complications after pancreaticoduodenectomy?

PMID- 11505072
TI  - Presence and distribution of sensory nerve fibers in human peritoneal adhesions.
AB  - OBJECTIVE: To assess the distribution and type of nerve fibers present in human
      peritoneal adhesions and to relate data on location and size of nerves with
      estimated age and with clinical parameters such as reports of chronic pelvic
      pain. SUMMARY BACKGROUND DATA: Peritoneal adhesions are implicated in the cause
      of chronic abdominopelvic pain, and many patients are relieved of their symptoms
      after adhesiolysis. Adhesions are thought to cause pain indirectly by restricting
      organ motion, thus stretching and pulling smooth muscle of adjacent viscera or
      the abdominal wall. However, in mapping studies using microlaparoscopic
      techniques, 80% of patients with pelvic adhesions reported tenderness when these
      structures were probed, an observation suggesting that adhesions themselves are
      capable of generating pain stimuli. METHODS: Human peritoneal adhesions were
      collected from 25 patients undergoing laparotomy, 20 of whom reported chronic
      pelvic pain. Tissue samples were prepared for histologic, immunohistochemical,
      and ultrastructural analysis. Nerve fibers were characterized using antibodies
      against several neuronal markers, including those expressed by sensory nerve
      fibers. In addition, the distribution of nerve fibers, their orientation, and
      their association with blood vessels were investigated by acetylcholinesterase
      histochemistry and dual immunolocalization. RESULTS: Nerve fibers, identified
      histologically, ultrastructurally, and immunohistochemically, were present in all
      the peritoneal adhesions examined. The location of the adhesion, its size, and
      its estimated age did not influence the type of nerve fibers found. Further,
      fibers expressing the sensory neuronal markers calcitonin gene-related protein
      and substance P were present in all adhesions irrespective of reports of chronic
      abdominopelvic pain. The nerves comprised both myelinated and nonmyelinated axons
      and were often, but not invariably, associated with blood vessels. CONCLUSIONS:
      This study provides the first direct evidence for the presence of sensory nerve
      fibers in human peritoneal adhesions, suggesting that these structures may be
      capable of conducting pain after appropriate stimulation.

PMID- 11505074
TI  - The difficulties in carrying out this study comparing three established
      modalities of preventing recurrent variceal hemorrhage in patients with portal
      hypertension.

PMID- 11505075
TI  - Thrombelastography.
AB  - Thrombelastography is a 'near patient' test of coagulation. It is easy to perform
      and can provide information on a patient's coagulation status within 30 min.
      Despite more than 25 years of clinical experience, however, several basic
      questions relating thromboelastograph (TEG) parameters to standard coagulation
      tests remain unanswered, and the value of the TEG is established only in the
      setting of orthotopic liver transplantation and cardiopulmonary bypass surgery.
      This review will focus on the principles and practise of the TEG(R), and data
      supporting the current accepted uses. Potential future uses will also be
      discussed including evaluation of hypercoagulable states, and investigating the
      mechanism of coagulopathies due to drugs or disease that standard tests have
      failed to unravel.

PMID- 11505076
TI  - Human mesothelial cells express tissue factor when switched to proliferating
      state. Pharmacological modulation in vitro.
AB  - Covering the inner surface of small-diameter arterial prostheses with endothelial
      cells (ECs) has been proposed as a means of improving biocompatibility and
      thrombosis resistance. Because the availability of autologous ECs is limited,
      autologous human mesothelial cells (HMCs) have been suggested as a substitute for
      ECs. However, HMCs express tissue factor (TF) in vitro, a deleterious
      characteristic in vivo. We investigated the distribution of TF antigen and of its
      inhibitor, tissue factor pathway inhibitor, on HMCs and the effect of
      pharmacological agents on TF expression. TF antigen was measured by enzyme-linked
      immunosorbent assay and localized by confocal microscopy. Three distinct pools of
      TF antigen were demonstrated: within the cells, at the cell surface, and in the
      extracellular matrix. The effects of ilomedin (10 microg/ml) and heparin (500
      U/ml), known to affect procoagulant activity, were evaluated by incubating HMCs
      for 24 h with or without these agents. Ilomedin, but not heparin, decreased TF
      antigen expression by 30% (P < 0.05). Despite the theoretical potential of HMCs
      as a vascular prosthesis lining, TF expression by HMCs remains a major drawback.
      A technique capable of blocking TF expression until the HMCs return to their
      resting state is needed. Genetic manipulation of HMCs may hold promise for such a
      technique.

PMID- 11505077
TI  - The effects of danaparoid, dalteparin and heparin on tissue factor-induced
      experimental disseminated intravascular coagulation and bleeding time in the rat.
AB  - Danaparoid and heparin, on the basis of anti-activated factor X (anti-FXa)
      activity, were equipotent in accelerating the rate of interaction of FXa and
      antithrombin III. In rat tissue factor-induced disseminated intravascular
      coagulation (DIC) models, an intravenous administration of danaparoid inhibited
      the decrease in plasma fibrinogen and platelet counts and the increase in serum
      fibrinogen degradation products. Expressed on the basis of anti-FXa activity,
      these effects were comparable with those of dalteparin and heparin. In rat
      mesenteric small artery and vein, less bleeding was observed after intravenous
      administration of danaparoid than after dalteparin or heparin. Danaparoid did not
      affect adenosine diphosphate- or collagen-induced platelet aggregation, and
      showed weaker inhibitory effects on aggregation induced by thrombin, or collagen
      + thrombin, than did dalteparin or heparin. These findings suggest that
      danaparoid may be useful for the prevention of DIC and has less tendency to cause
      bleeding than dalteparin or heparin, probably as a result of its weaker ability
      to inhibit platelet aggregation.

PMID- 11505078
TI  - Seasonal variation of some metabolic and haemostatic risk factors in subjects
      with and without coronary artery disease.
AB  - Acute myocardial infarction (AMI) is more frequent in winter months than in
      summer months. The aetiologic mechanisms underlying this seasonal pattern are
      poorly understood. We investigate whether seasonal variation of metabolic and
      haemostatic coronary risk factors exists, and whether this variation is more
      pronounced in subjects with coronary artery disease (CAD). In 82 subjects (47
      free of clinical signs of CAD and in 35 survivors of AMI), measurements of body
      mass index (BMI), lipoproteins, glucose, insulin, plasminogen activator inhibitor
      1, tissue-type plasminogen activator (t-PA), euglobulin clot lysis time,
      fibrinogen, and platelet count were performed twice in the cold months (December
      and March) and twice in the warm months (June and September). Significantly
      higher BMI (26.8 versus 26.2 kg/m2, P < 0.01), glucose (5.5 versus 5.1 mmol/l, P
      < 0.01), total cholesterol (5.61 versus 5.32 mmol/l, P < 0.05), low-density
      lipoprotein cholesterol (3.63 versus 3.34 mmol/l, P < 0.05), triglycerides (1.79
      versus 1.61 mmol/l, P < 0.01), Lp(a) (270.7 versus 237.5 mg/l, P < 0.01),
      fibrinogen level (3.50 versus 2.95 g/l, P < 0.00001), platelet count (212 x 10(9)
      versus 173 x 10(9)/l, P < 0.01) and significantly lower high-density lipoprotein
      cholesterol level (1.22 versus 1.28 mmol/l, P < 0.05) were observed in the cold
      months compared with the warm months. Significant seasonal variation of t-PA
      activity (1.19 versus 0.87 IU/ml, P = 0.015) and t-PA antigen (8.5 versus 7.3
      ng/ml, P = 0.05) was demonstrated only in subjects with CAD. Clustering of peak
      values of several metabolic and haemostatic coronary risk factors was observed in
      winter months. This variation might be of aetiopathogenetic importance for the
      seasonal pattern of acute myocardial infarction.

PMID- 11505079
TI  - Prophylactic therapy with enoxaparin during L-asparaginase treatment in children
      with acute lymphoblastic leukemia.
AB  - Forty-one consecutive children with acute lymphoblastic leukemia (ALL) received
      prophylaxis therapy with the low molecular weight heparin (LMWH) enoxaparin
      during L-asparaginase treatment. Enoxaparin was given every 24 h subcutaneously
      at a median dose of 0.84 mg/kg per day (range, 0.45-1.33 mg/kg per day) starting
      at the first dose of L-asparaginase until 1 week after the last dose. Molecular
      analysis for thrombophilic polymorphisms documented prothrombin G20210A mutation
      in 3/27 (11%), homozygosity for MTHFR C677T mutation in 5/27 (18.5%, and
      heterozygosity for factor V Leiden mutation in 5/27 (18.5%) children. There were
      no thrombotic events during 76 courses of L-asparaginase in 41 patients who had
      received enoxaparin. One patient suffered brain infarct 7 days after enoxaparin
      was stopped. There were no bleeding episodes. In a historical control group of 50
      ALL children who had not received prophylactic enoxaparin during L-asparaginase
      treatment, two had thromboembolisms (one deep vein thrombosis and one pulmonary
      embolism). Enoxaparin is safe and seems to be effective in prevention of
      thromboembolism in ALL patients during L-asparaginase therapy. This study
      provides pilot data for a future randomized trial of the use of LMWH during ALL
      therapy for the prevention of asparaginase-associated thrombotic events.

PMID- 11505080
TI  - Low molecular weight heparin prevents activation of coagulation in a hypobaric
      environment.
AB  - It is commonly thought that people are at increased risk of venous thrombosis
      during air flights, but the magnitude of the risk is unknown. Suggested risk
      factors are hypobaric hypoxia, stasis, and dehydration. In a previous
      experimental study, we found immediate activation of coagulation as determined by
      the levels of prothrombin fragments 1 + 2 (F(1 + 2)) and thrombin-antithrombin
      complex (TAT) after rapid exposure to a hypobaric and hypoxic environment (76
      kPa). The aim of the present study was to examine the ability of low molecular
      weight heparin (LMWH) to prevent such activation. Twelve healthy male volunteers
      were given 40 mg enoxaparin as a single subcutaneous injection 1 h prior to
      exposure from 96.3 to 76 kPa. We found no activation of coagulation as judged by
      F(1 + 2) or TAT. Anti-activated factor X activity levels and release of tissue
      factor pathway inhibitor was normal. We conclude that high prophylactic doses of
      a LMWH most probably prevent activation of coagulation in a hypobaric
      environment.

PMID- 11505081
TI  - Quantitation of the factor VII- and single-chain plasminogen activator-activating
      protease in plasmas of healthy subjects.
AB  - Plasma samples of 189 healthy subjects were investigated for antigen levels of
      the recently reported factor VII- and single-chain plasminogen activator
      activating protease (FSAP) and the corresponding pro-urokinase activating
      potencies. While the age of donors had no significant effect on the investigated
      parameters, female plasmas revealed a trend to higher antigen contents and
      activity levels. Surprisingly, as much as 9% of all samples contained
      significantly reduced single-chain urinary plasminogen activator activating
      potential, whereas antigen concentrations were normal. Additionally, 1% of the
      plasmas was found to decrease in both FSAP antigen and activity contents. FSAP of
      three subjects displaying reduced activities throughout a follow-up period of 6
      months were purified from plasmas and were characterized. As compared with pool
      plasma derived FSAP, investigation of the individual preparations confirmed their
      reduced potency to activate pro-urokinase. However, factor VII activation was not
      affected. It is speculated that the FSAP binding site for single-chain
      plasminogen activators is affected, potentially by as yet unknown polymorphism(s)
      or mutation(s).

PMID- 11505082
TI  - Epidermal growth factor enhances lipopolysaccharide-induced procoagulant activity
      on the cell surface of endothelial cells.
AB  - Endotoxin [lipopolysaccharide (LPS)] and some cytokines are known to induce
      tissue factors with the expression of procoagulant activity (PCA) on the cell
      surface of endothelial cells. We established a modified quantitative procedure
      for PCA expressed on the cell surface, and studied the effects of serum and
      epidermal growth factor (EGF) on the LPS-induced activation of PCA on cultured
      human umbilical vein endothelial cells. Meanwhile, human umbilical cord serum
      elevated PCA more than either fetal bovine serum (FBS) or human adult serum.
      Generally, the existence of LPS raises the concentration of EGF in the blood,
      since monocytes and other types of cells express EGF and release it into the
      vessel by LPS stimulation. Although 10 ng/ml EGF did not induce PCA even in the
      presence of 10% FBS, it enhanced LPS-induced PCA under the same conditions. In
      the presence of 10% FBS, PCA induced both by LPS alone and by LPS + EGF was
      reduced the same amount by the protein kinase C (PKC) inhibitors H7 and H8. These
      results suggest that the serum contains some cofactor other than EGF, and that
      EGF enhanced this LPS-induced PCA independent of the cofactor through PKC
      involved signaling.

PMID- 11505083
TI  - Effects of sarpogrelate hydrochloride on adenosine diphosphate- or collagen
      induced platelet responses in arteriosclerosis obliterans.
AB  - To evaluate the effects of the 5-HT2 receptor antagonist sarpogrelate
      hydrochloride (sarpogrelate) on platelet responses in arteriosclerosis obliterans
      (ASO), we examined platelet aggregation and its relationships to platelet-derived
      growth factor (PDGF), soluble P-selectin (sP-selectin), and transforming growth
      factor-beta 1 (TGF-beta1). Circulating plasma levels of PDGF and sP-selectin in
      13 patients with ASO after 1 week of medication with sarpogrelate were
      significantly lower than those before medication. In contrast, circulating plasma
      levels of TGF-beta1 after medication were significantly higher than those before
      medication. When platelet-rich plasma obtained from ASO patients after medication
      was stimulated with adenosine diphosphate (ADP) or collagen, platelet aggregation
      was suppressed compared with rates before medication. Significant decreases in
      levels of PDGF, sP-selectin and TGF-beta1 released from platelets in response to
      5 micromol/l ADP and 1 microg/ml collagen after taking of sarpogrelate were
      found. There were close correlations between platelet aggregation and respective
      molecules released from platelets. In conclusion, since platelet activation is
      involved in pathogenesis of thrombotic disease, sarpogrelate may suppress the
      development of obstructive arteriosclerosis. PDGF and TGF-beta1, as well as sP
      selectin, appear to be useful markers for clinical evaluation of anti-platelet
      drugs.

PMID- 11505084
TI  - The clinical relevance of the citrate effect on International Normalized Ratio
      determinations depends on the reagent and instrument combination used.
AB  - Multiple studies have shown that the two different citrate concentrations in
      common use as the anticoagulant in blood collection for haemostasis assays can
      affect the results obtained with the prothrombin time assay. It is clear from the
      literature that there is considerable variability in the results obtained using
      different instrument-reagents combinations, but the clinical relevance of these
      differences is unclear. Most of the studies have used an optical system for end
      point detection. This study reports on the citrate sensitivity using mechanical
      end-point detection. Using two different reagents, one previously shown to be
      citrate sensitive on optical systems (Neoplastin CI plus) and a citrate
      insensitive reagent (Neoplastin CI), we demonstrate that the effect of using
      different citrate concentrations (0.105 or 0.129 mol/l) has statistically
      significant but clinically irrelevant effects on the International Normalized
      Ratio using a mechanical instrument (STA)-reagent combination (mean percentage
      difference in results, 1.9 and 3.8% respectively). This demonstrates that the
      citrate effect is both instrument type and reagent dependent. Every reagent and
      instrument combination needs to be tested to see whether any citrate effect
      exists. In a secondary study, it was shown that the international reference
      rabbit thromboplastin (CRM 149(s)) was not citrate-concentration sensitive.

PMID- 11505085
TI  - A new global test for the evaluation of the activated factor II-antithrombin
      system.
AB  - We developed a new simple test to evaluate the global function of the activated
      factor II-antithrombin system. The new test measures the clotting time of plasma
      samples after the addition of a reagent containing a snake venom (Echis
      carinatus) that can activate prothrombin, with (Ta) and without (To) heparin. The
      prolongation of clotting times (Ta - To) is directly related to the function of
      the activated factor II-antithrombin system. The presence of quantitative or
      functional defects of the natural inhibitors (antithrombin and heparin co-factor
      II), or high levels of factor II and/or fibrinogen, can trigger a resistance to
      the inhibition of activated factor II. This new test was used to examine 134
      thrombophilic patients as well as 157 normal subjects as controls. The results
      obtained confirm that the presence of abnormalities relating to the activated
      factor II-antithrombin system causes a resistance to activated factor II
      inhibition even if a significant number of patients was found to have a
      resistance that could not be accounted for. Since the new test can be easily
      performed automatically and has a good inter- and intra-assay variation
      coefficient (CV < 4%) it is useful for evaluating the global function of the
      activated factor II-antithrombin system in screening thrombophilic patients,
      alongside the tests already known and used to diagnose these patients.

PMID- 11505086
TI  - Low plasma protein Z levels in patients with antiphospholipid antibodies.

PMID- 11505087
TI  - Enhancement of tissue-type plasminogen activator (t-PA)-mediated plasminogen
      activation on the surface of endothelial cells by t-PA receptor.

PMID- 11505088
TI  - Compassionate end-of-life care in the intensive care unit.

PMID- 11505114
TI  - Effect of postpyloric feeding on gastroesophageal regurgitation and pulmonary
      microaspiration: results of a randomized controlled trial.
AB  - OBJECTIVE: To determine the extent to which postpyloric feeding reduces
      gastroesophageal regurgitation and pulmonary microaspiration in critically ill
      patients. DESIGN: Randomized trial. SETTING: A medical/surgical intensive care
      unit at a tertiary care hospital. PARTICIPANTS: Intensive care unit patients were
      expected to remain ventilated >72 hrs. We excluded patients with esophageal,
      gastric, or small bowel surgery in the last week and patients with overt or
      clinically significant gastrointestinal bleeding. We studied 33 patients; 42.4%
      were female, mean age (sd) was 59.2 (+/- 16.8) yrs, and mean Acute Physiology and
      Chronic Health Evaluation II score was 22.5 (7.8). INTERVENTIONS: Patients were
      randomized to gastric or postpyloric enteral feeds. Technetium 99-sulphur colloid
      was added to the feeds for 6 hrs of each of the first 3 days on study.
      MEASUREMENTS AND RESULTS: We sampled the oropharynx and trachea hourly for the 6
      hrs per day that patients received radioisotope-labeled enteral feeds, and the
      level of radioactivity in these specimens was measured. We defined an episode of
      gastroesophageal regurgitation and microaspiration as an increase in
      radioactivity >100 counts per minute/g. Patients fed into the stomach had more
      episodes of gastroesophageal regurgitation (39.8% vs. 24.9%, p =.04) and trended
      toward more microaspiration (7.5% vs. 3.9%, p =.22) compared with patients fed
      beyond the pylorus. When the logarithmic mean of the radioactivity count was
      compared across groups, there was a trend toward an increase in gastroesophageal
      regurgitation (3.7 vs. 2.9 counts/g, p =.22) and a trend toward increased
      microaspiration (1.9 vs. 1.4 counts/g, p =.09) in patients fed into the stomach.
      Patients who had gastroesophageal regurgitation were much more likely to aspirate
      than patients who did not have gastroesophageal regurgitation (odds ratio: 3.2;
      95% confidence interval: 1.36, 7.77). CONCLUSIONS: Feeding beyond the pylorus is
      associated with a significant reduction in gastroesophageal regurgitation and a
      trend toward less microaspiration.

PMID- 11505116
TI  - Radiologic determination of intravascular volume status using portable, digital
      chest radiography: a prospective investigation in 100 patients.
AB  - OBJECTIVE: To answer the following questions: Can the digital chest roentgenogram
      (CXR) be used to differentiate patients' volume status? Do clinical data alter
      radiologists' accuracy in interpreting the digital CXR? DESIGN: Prospective
      cohort study. SETTING: Nine adult intensive care units of a tertiary care medical
      center. PATIENTS: One hundred thirty-five consecutive patients with pulmonary
      artery catheters, of whom 35 were excluded because of unacceptable pulmonary
      artery occlusion pressure (PAOP) tracings. METHODS: Each patient had a portable,
      anteroposterior, supine digital CXR. Clinicians evaluated volume status and then
      measured hemodynamic data within 1 hr of the CXR. Digital CXRs were independently
      interpreted on two separate occasions (with and without clinical information) by
      three experienced chest radiologists, and these interpretations were compared
      with hemodynamic data. RESULTS: Of the 100 patients, 39 had PAOP >18 mm Hg,
      whereas 61 had PAOP <18 mm Hg. Radiologists' accuracy in differentiating volume
      status increased with incorporation of clinical data (56% without vs. 65% with
      clinical data, p =.009). Using objective receiver operating characteristic
      derived cutoffs of 70 mm for vascular pedicle width and 0.55 for cardiothoracic
      ratio, radiologists' accuracy in differentiating PAOP >18 mm Hg from PAOP <18 mm
      Hg was 70%. The intrareader and the inter-reader correlation coefficients were
      very high. The likelihood ratio of the CXR in determining volume status using the
      objective vascular pedicle width and cardiothoracic ratio measures was 3.1 (95%
      confidence interval, 1.9-6.0), significantly higher than subjective CXR
      interpretations with and without clinical data (p <.001). CONCLUSIONS:
      Differentiating intravascular volume status with portable, supine, digital CXRs
      may be improved by using objective cutoffs of vascular pedicle width >70 mm and
      cardiothoracic ratio >0.55 or by incorporating clinical data.

PMID- 11505117
TI  - Ringer's ethyl pyruvate solution ameliorates ischemia/reperfusion-induced
      intestinal mucosal injury in rats.
AB  - OBJECTIVE: Pyruvate has been shown to be protective in numerous in vitro and in
      vivo models of oxidant-mediated cellular or organ system injury. Unfortunately,
      the usefulness of pyruvate as a therapeutic agent is abrogated by its very poor
      stability in solution. In an effort to take advantage of the ability of pyruvate
      to scavenge reactive oxygen species while avoiding the problems associated with
      the instability of pyruvate in solution, we sought to determine whether a simple
      derivative, ethyl pyruvate, would be protective in an animal model of reactive
      oxygen species-mediated tissue injury, namely mesenteric ischemia and reperfusion
      in rats. DESIGN: Prospective, randomized trial. SETTING: Animal research center.
      SUBJECTS: Male Sprague-Dawley rats. INTERVENTIONS: Under general anesthesia, rats
      were subjected to 60 mins of mesenteric ischemia followed by 60 mins of
      reperfusion. Controls (n = 6) received intravenous lactated Ringer's solution
      according this dosing schedule: 1.5 mL/kg bolus before ischemia, 3.0 mL/kg bolus
      before resuscitation, and 1.5 mL.kg-1.hr-1 by continuous infusion. Two
      experimental groups received similar volumes of either pyruvate (n = 6 each) or
      ethyl pyruvate (n = 9) solution made up exactly like lactated Ringer's solution
      except for the substitution of either pyruvate or ethyl pyruvate for lactate,
      respectively. MEASUREMENTS AND MAIN RESULTS: To obtain tissues for assessing
      mucosal permeability and histology, five 10-cm long segments of small intestine
      were obtained at the following time points: baseline, after 30 and 60 mins of
      ischemia, and after 30 and 60 mins of reperfusion. Mucosal permeability to
      fluorescein isothiocyanate dextran (molecular weight 4000 Da) was assessed ex
      vivo by using an everted gut sac method. Compared with controls, treatment of
      rats with either pyruvate solution or ethyl pyruvate solution significantly
      ameliorated the development of intestinal mucosal hyperpermeability during the
      reperfusion. Treatment with ethyl pyruvate solution also significantly decreased
      the extent of histologic mucosal damage after mesenteric reperfusion.
      CONCLUSIONS: Treatment with Ringer's ethyl pyruvate solution ameliorated
      structural and functional damage to the intestinal mucosa in a rat model of
      mesenteric ischemia/reperfusion. Ethyl pyruvate solution warrants further
      evaluation as a novel therapeutic agent for preventing oxidant-mediated injury in
      various disease states.

PMID- 11505119
TI  - Enoximone in contrast to dobutamine improves hepatosplanchnic function in fluid
      optimized septic shock patients.
AB  - OBJECTIVE: To investigate the impact of dobutamine and enoximone on
      hepatosplanchnic perfusion and function in fluid-optimized septic patients.
      DESIGN: Prospective, randomized, double-blinded interventional study. SETTING:
      Intensive care unit of a university hospital. PATIENTS: Forty-eight septic shock
      patients were examined within 12 hrs after onset of septic shock. Patients were
      conventionally resuscitated, achieving an optimal pulmonary artery occlusion
      pressure at which the left ventricular stroke work was on the maximal plateau.
      Liver blood flow was estimated by venous suprahepatic catheterization using the
      continuous indocyanine green infusion technique. Microsomal liver function was
      assessed by the plasma appearance of monoethylglycinexylidide, and release of
      hepatic tumor necrosis factor-alpha (TNF-alpha) was measured to estimate the
      severity of hepatic ischemia-reperfusion syndrome. INTERVENTIONS: Patients were
      randomly treated with dobutamine or enoximone. Within the first 10 hrs after
      baseline measurements, the dosage was increased until no further increase in the
      left ventricular stroke work index occurred. Then, positive inotropes were kept
      constant throughout the study. MEASUREMENTS AND MAIN RESULTS: Measurements were
      performed at baseline and after 12 and 48 hrs after baseline measurements.
      Cardiac index, systemic oxygen delivery, systemic oxygen consumption, and liver
      blood flow increased significantly in both groups during treatment (p <.01)
      without a significant difference between groups. Fractional liver blood flow
      (liver blood flow/cardiac index) did not change in the enoximone group and showed
      a significant but only minor (median, 10%) decrease in the dobutamine group (p
      <.05 after 12 hrs and p <.01 after 48 hrs vs. baseline). After 12 hrs of
      enoximone treatment, monoethylglycinexylidide kinetics and hepatosplanchnic
      oxygen consumption demonstrated a significant increase (p <.05). The release of
      hepatic TNF-alpha after 12 hrs of dobutamine treatment was twice as high (p <.05)
      as during enoximone. CONCLUSION: The increase in hepatosplanchnic oxygen
      consumption, together with an increased lignocaine metabolism and decreased
      release of hepatic TNF-alpha, indicates improved hepatosplanchnic function and
      antiinflammatory properties after 12 hrs of enoximone treatment. Therefore, if
      the inflammatory response should be attenuated in high-risk patients,
      administration of enoximone in fluid-optimized septic shock patients may be
      favorable compared with dobutamine.

PMID- 11505120
TI  - Use of dopamine in acute renal failure: a meta-analysis.
AB  - OBJECTIVE: To determine whether low-dose dopamine administration reduces the
      incidence or severity of acute renal failure, need for dialysis, or mortality in
      patients with critical illness. DATA SOURCES AND STUDY SELECTION: We performed a
      MEDLINE search of literature published from 1966 to 2000 for studies addressing
      the use of dopamine in the prevention and/or treatment of renal dysfunction. DATA
      EXTRACTION: Data were abstracted regarding design characteristics, population,
      intervention, and outcomes. Results of individual randomized clinical trials were
      pooled using a fixed effects model and a Mantel-Haenszel weighted chi-square
      analysis. DATA SYNTHESIS: We identified a total of 58 studies (n = 2149). Of
      these, outcome data were reported in 24 studies (n = 1019) and 17 of these were
      randomized clinical trials (n = 854). Dopamine did not prevent mortality,
      (relative risk, 0.90 [0.44-1.83]; p =.92), onset of acute renal failure (relative
      risk, 0.81 [0.55-1.19]; p =.34), or need for dialysis, (relative risk, 0.83 [0.55
      1.24]; p =.42). There was sufficient statistical power to exclude any large
      (>50%) effect of dopamine on the risk of acute renal failure or need for
      dialysis. CONCLUSIONS: The use of low-dose dopamine for the treatment or
      prevention of acute renal failure cannot be justified on the basis of available
      evidence and should be eliminated from routine clinical use.

PMID- 11505121
TI  - Comparison of initial distribution volume of glucose and plasma volume in
      thoracic fluid-accumulated patients.
AB  - OBJECTIVE: We have reported that initial distribution volume of glucose indicates
      the central extracellular fluid volume in the presence of fluid gain or loss. The
      purpose of this study was to describe changes in initial distribution volume of
      glucose, plasma volume determined by the indocyanine green dilution method (PV
      ICG), and thoracic fluid content by thoracic electrical bioimpedance in patients
      with or without apparent thoracic fluid accumulation in the absence of pleural
      effusion. We also sought to test whether initial distribution volume of glucose
      rather than PV-ICG mirrors thoracic fluid content. DESIGN: Prospective, clinical
      study. SETTING: General intensive care unit. PATIENTS: Eleven consecutive
      patients with apparent thoracic fluid accumulation as judged by thoracic fluid
      content >0.05/ohm and underlying pathology and 20 consecutive acute myocardial
      infarction patients within 24 hrs after its onset were selected for study. None
      of the acute myocardial infarction patients had thoracic fluid content >0.05/ohm.
      INTERVENTIONS: Five grams of glucose and 25 mg of indocyanine green were
      administered simultaneously to calculate initial distribution volume of glucose
      and PV-ICG daily for the fluid-accumulated patients, and the same dosages were
      administered to the acute myocardial infarction patients immediately after their
      admission to the intensive care unit after percutaneous coronary angioplasty.
      Only the data on the day of the maximal and minimal thoracic fluid content in the
      fluid-accumulated patients were used for the study. The relationship between
      these two fluid volumes and thoracic fluid content was evaluated in the two
      patient groups. MEASUREMENTS AND MAIN RESULTS: Initial distribution volume of
      glucose and thoracic fluid content rather than PV-ICG and thoracic fluid content
      moved together in the same direction in each fluid-accumulated patient. Neither
      pulmonary artery occlusion pressure, central venous pressure, nor PV-ICG produced
      a better correlation with cardiac index when compared with initial distribution
      volume of glucose in patients with or without thoracic fluid accumulation.
      CONCLUSIONS: We suggest that initial distribution volume of glucose rather than
      PV-ICG is a better indicator of the intrathoracic blood volume status, even
      although intravenously administered glucose cannot stay in the intravascular
      compartment.

PMID- 11505122
TI  - Quality of life after severe bacterial peritonitis and infected necrotizing
      pancreatitis treated with open management of the abdomen and planned re
      operations.
AB  - OBJECTIVE: To determine quality of life after severe bacterial peritonitis and
      infected necrotizing pancreatitis treated with open management of the abdomen and
      planned re-operations. DESIGN: Retrospective chart review. SETTING: University
      hospital intensive care unit, general wards, and outpatient department. PATIENTS:
      Forty-one patients who survived severe bacterial peritonitis and infected
      necrotizing pancreatitis treated with open management of the abdomen and planned
      re-operations. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Over a period
      of 7 yrs, 95 patients underwent open management of the abdomen and planned re
      operations for severe bacterial peritonitis and infected necrotizing
      pancreatitis. Thirty-nine patients died during the initial intensive care unit
      stay and 12 as a result of nonperitonitis-related systemic diseases after
      discharge. Four patients were lost or excluded from final analysis. Long-term
      morbidity and quality of life using Karnofsky and Rankin scores at discharge and
      at follow-up at least 1 yr after discharge (mean: 4 yrs) and the Sickness Impact
      Profile (SIP) were determined. The remaining 41 patients reviewed showed
      significant long-term morbidity, including dysfunction of the abdominal wall
      resulting from herniation, persistent polyneuropathy, and mental disorders
      needing psychiatric support. Patients having persistent polyneuropathy and, to a
      lesser extent, mental disorders, showed significantly lower Karnofsky, higher
      Rankin, and higher SIP scores. After discharge, performance status of patients
      improved significantly, as shown by higher Karnofsky and lower Rankin scores,
      and, because Karnofsky and Rankin scores are closely related to SIP scores,
      higher SIP scores. Especially in measuring quality of life in terms of social and
      role management, assessment of the SIP proved to have additional value.
      CONCLUSIONS: About three-quarters of patients who survive open management of the
      abdomen and planned re-operations for severe bacterial peritonitis and infected
      necrotizing pancreatitis regain a good quality of life. Some patients, especially
      those who suffer from persistent polyneuropathy and mental disorders, show
      restrictions in daily life.

PMID- 11505124
TI  - Plasma clearance of iodine contrast media as a measure of glomerular filtration
      rate in critically ill patients.
AB  - OBJECTIVE: The selection of the optimal method for assessing renal function
      relies on the accuracy of the technique. Plasma clearance of nonradioactive
      iodine contrast media (i.e., iohexol or iopromide) has been suggested as a
      reliable alternative to the renal clearance of inulin for estimating glomerular
      filtration rate (GFR). The accuracy of this method when used with critically ill
      patients displaying different levels of renal function in an intensive care unit
      (ICU) has not, until now, been examined. DESIGN: The accuracy of double- and
      multiple-point iohexol or iopromide plasma clearances was compared with that of
      already established techniques for measuring GFR (creatinine clearance, formula
      clearance by Cockcroft and Gault) and with that of inulin clearance, which is
      regarded as the gold standard for the measurement of GFR. PATIENTS: Values were
      obtained from 31 ICU patients who exhibited a wide range of renal function (serum
      creatinine: 0.6-6.7 mg/dL). MEASUREMENTS: Inulin clearance was performed using
      the constant-infusion technique. Creatinine clearance was determined from 24-hr
      urine samples. The clearance formula was calculated according to Cockcroft and
      Gault's formula. Iohexol or iopromide were applied as a single intravenous dose,
      and blood samples were taken up to 6 hrs after the injection. Iodine
      concentrations were determined by radiographic fluorescence. RESULTS: Plasma
      clearance of iohexol/iopromide measured after the single injection of contrast
      media and that of the conventional inulin clearance was almost identical (y =
      0.971x + 7.65, r2 =.96; n = 31). Two-point clearance of iohexol/iopromide (double
      sampling technique) was as reliable as the three-point clearance (three-slope
      intercept method, y = 0.995x + 0.62, r2 =.999; n = 18). With respect to inulin
      clearance, GFR measurements determined by creatinine clearance or according to
      the formula given by Cockcroft and Gault revealed errors that increased
      proportionally (y = 1.03x, r2 =.88; n = 27; and y = 0.93x, r2 =.62; n = 31,
      respectively). It could also be shown that the accuracy of GFR measurements
      involving plasma clearance of iohexol was not greatly affected by the degree of
      renal insufficiency or the route by which contrast media were applied.
      CONCLUSION: These findings indicate that the determination of plasma clearance of
      iohexol/iopromide is a simple, rapid, and accurate method that can indeed be used
      for estimating GFR in ICU patients with normal renal function or even different
      degrees of renal insufficiency.

PMID- 11505125
TI  - Acute cor pulmonale in acute respiratory distress syndrome submitted to
      protective ventilation: incidence, clinical implications, and prognosis.
AB  - CONTEXT: The incidence of acute cor pulmonale (ACP), a frequent and usually
      lethal complication of acute respiratory distress syndrome (ARDS) during
      traditional respiratory support, has never been re-evaluated since protective
      ventilation gained acceptance. OBJECTIVE: We performed a longitudinal
      transesophageal echocardiographic (TEE) study to determine whether this
      incidence, and its severe implications for prognosis, might have changed in our
      unit as we altered respiratory strategy. DESIGN: Prospective open clinical study.
      SETTING: Medical intensive care unit of a university hospital. PATIENTS: Seventy
      five consecutive ARDS patients given respiratory support with airway pressure
      limitation (plateau pressure < or =30 cm H2O). INTERVENTIONS: ACP was defined as
      a ratio of right ventricular end-diastolic area to left ventricular end-diastolic
      area in the long axis >0.6 associated with septal dyskinesia in the short axis
      during TEE examination. RESULTS: Normal right ventricular function was present in
      56 patients, whereas right ventricular dysfunction was observed in 19 patients
      after 2 days of respiratory support. ACP was associated with pulmonary artery
      hypertension, increased heart rate, and decreased stroke index. Significant
      impairment of left ventricular diastolic function was also seen. All echo-Doppler
      abnormalities were reversible in patients who recovered, and the mortality rate
      was the same in both groups (32%). However, ACP patients who recovered required a
      longer period of respiratory support. A multivariate analysis individualized
      Paco2 level as the sole factor independently associated with ACP, suggesting that
      ACP development in ARDS is influenced by the severity of lung damage and/or the
      respiratory strategy. CONCLUSION: Evaluation of right ventricular function by TEE
      in a group of 75 ARDS patients submitted to protective ventilation revealed the
      persistence of a 25% incidence of ACP, resulting in detrimental hemodynamic
      consequences associated with tachycardia. However, ACP was reversible in patients
      who recovered and did not increase mortality.

PMID- 11505126
TI  - Clinical relevance of caspase-1 activated cytokines in acute pancreatitis: high
      correlation of serum interleukin-18 with pancreatic necrosis and systemic
      complications.
AB  - OBJECTIVES: There is recent experimental evidence that caspase-1 activation plays
      an instrumental role in the pathomechanism of severe acute pancreatitis. Besides
      interleukin-1beta, interleukin-18, a recently described proinflammatory cytokine,
      is cleaved into its biologically active form by caspase-1 as well. Interleukin-18
      is known to have potent properties concerning the activation of the Th1
      lymphocyte subset via costimulation of interferon-gamma production. In contrast
      to interleukin-1beta, little is known about the clinical impact of interleukin-18
      in the course of acute pancreatitis. DESIGN: Cohort study comparing patients with
      mild and severe acute pancreatitis associated with local and systemic
      complications during the course of the disease. SETTING: Surgical and
      anesthesiological intensive care unit as well as wards of the department of
      general surgery. PATIENTS: We included 68 patients with acute pancreatitis in the
      present study. In terms of local complications, pancreatic necrosis was present
      in 37 patients, of whom 21 developed pancreatic infections. Systemic
      complications included pulmonary, renal, or cardiocirculatory insufficiency and
      were observed in 40, 18, and 25 patients, respectively. Severe multiple-organ
      dysfunction syndrome involving all three organ systems occurred in 18 patients,
      all suffering from pancreatic necrosis. INTERVENTIONS: Serum samples were
      collected over 14 consecutive days after study inclusion. Ascites or
      peripancreatic exudate was obtained by ultrasound-guided fine needle aspiration
      in 14 cases. Sera and local aspirates were stored at -70 degrees C until
      analysis. MEASUREMENTS AND RESULTS: Interleukin-18 and interferon-gamma were
      measured by commercially available enzyme-linked immunosorbent assays.
      Interleukin-18 concentrations were significantly increased after the fourth day
      of disease onset until the end of the observation period in patients who
      developed pancreatic necrosis and systemic complications such as pulmonary,
      renal, and cardiocirculatory failure as well as severe multiple-organ dysfunction
      syndrome. However, no correlation was found between the development of pancreatic
      infections and interleukin-18 concentrations. In contrast with interleukin-18,
      interferon-gamma concentrations did not show any significant difference with
      respect to the presence or absence of either systemic or local complications.
      Local interleukin-18 concentrations in ascites or peripancreatic exudate were up
      to 20-fold higher than systemic concentrations, whereas interferon-gamma
      concentrations did not differ. CONCLUSIONS: Serum interleukin-18 concentrations
      are significantly elevated in patients with acute pancreatitis complicated by
      pancreatic necrosis and remote organ failure. The present data suggest an
      important role of caspase-1 dependent cytokine activation in the pathomechanism
      of severe acute pancreatitis beyond the experimental setting. In this context,
      interleukin-18 may serve as a potential target for new therapeutic approaches.

PMID- 11505128
TI  - Relationship of hypolipidemia to cytokine concentrations and outcomes in
      critically ill surgical patients.
AB  - OBJECTIVE: To determine the relationship of hypolipidemia to cytokine
      concentrations and clinical outcomes in critically ill surgical patients. DESIGN:
      Consecutive, prospective case series. SETTING: Surgical intensive care unit of an
      urban university hospital. PATIENTS: Subjects were 111 patients with a variety of
      critical illnesses, for whom serum lipid, lipoprotein, and cytokine
      concentrations were determined within 24 hrs of admission to a surgical intensive
      care unit. Controls were 32 healthy men and women for whom serum lipid,
      lipoprotein, and cytokine concentrations were determined. INTERVENTIONS: Blood
      samples were drawn on admission to the intensive care unit. Predetermined
      clinical outcomes including death, infection subsequent to intensive care unit
      admission, length of intensive care unit stay, and magnitude of organ dysfunction
      were monitored prospectively. MEASUREMENTS AND MAIN RESULTS: Measurements
      included total cholesterol, low-density lipoprotein cholesterol, high-density
      lipoprotein cholesterol, apolipoproteins A-I and B, phospholipid, triglyceride,
      interleukin-6, interleukin-10, soluble interleukin-2 receptor, tumor necrosis
      factor-alpha, and soluble tumor necrosis factor receptors p55 and p75. Mean serum
      lipid concentrations were extremely low: total cholesterol, 127 +/- 52 mg/dL; low
      density lipoprotein cholesterol, 75 +/- 41 mg/dL; high-density lipoprotein
      cholesterol, 29 +/- 15 mg/dL. Total, low-density lipoprotein, and high-density
      lipoprotein cholesterol concentrations and apolipoprotein concentrations
      inversely correlated with interleukin-6, soluble interleukin-2 receptor, and
      interleukin-10 concentrations, whereas the triglyceride concentration correlated
      positively with tumor necrosis factor soluble receptors p55 and p75. Clinical
      outcomes were related to whether the admission cholesterol concentration was
      above (n = 56) or below (n = 55) the median concentration of 120 mg/dL. Each of
      the clinical end points occurred between 1.9- and 3.5-fold more frequently in the
      very low cholesterol (<120 mg/dL) group. Nine patients (8%) died during the
      hospitalization. Seven of the nine patients who died had total cholesterol
      concentrations below the median concentration of 120 mg/dL. CONCLUSIONS: Low
      cholesterol and lipoprotein concentrations found in critically ill surgical
      patients correlate with interleukin-6, soluble interleukin-2 receptor, and
      interleukin-10 concentrations and predict clinical outcomes.

PMID- 11505129
TI  - Effects of intravenous fat emulsions on lung function in patients with acute
      respiratory distress syndrome or sepsis.
AB  - OBJECTIVE: To investigate whether rapid or slowly infused intravenous fat
      emulsions affect the ratio of prostaglandin I2/thromboxane A2 in arterial blood,
      pulmonary hemodynamics, and gas exchange. DESIGN: Prospective, controlled,
      randomized, crossover study. SETTING: Operative intensive care unit of a
      university hospital. PATIENTS: Eighteen critically ill patients. Ten patients
      were stratified with severe sepsis, and eight patients had acute respiratory
      distress syndrome (ARDS). INTERVENTIONS: Patients were assigned randomly to
      receive intravenous fat emulsions (0.4 x resting energy expenditure) over 6 hrs
      (rapid fat infusion) or 24 hrs (slow fat infusion) along with a routine
      parenteral nutrition regimen, by using a crossover study design. MEASUREMENTS AND
      MAIN RESULTS: Systemic and pulmonary hemodynamics as well as gas exchange
      measurements were recorded via respective indwelling catheters. Arterial
      thromboxane B2 and 6-keto-prostaglandin-F1alpha plasma concentrations were
      obtained by radioimmunoassay, and 6-keto-prostaglandin-F1alpha/thromboxane B2
      ratios (P/T ratios) were calculated. Data were collected immediately before and
      6, 12, 18, and 24 hrs after onset of fat infusion. In the ARDS group, P/T ratio
      increased by rapid fat infusion. Concomitantly, pulmonary shunt fraction,
      alveolar-arterial oxygen tension difference [P(a-a)o2]/Pao2, and cardiac index
      increased as well, whereas pulmonary vascular resistance and Pao2/Fio2 declined.
      After slow fat infusion, a decreased P/T ratio was revealed. This was accompanied
      by decreased pulmonary shunt fraction, lowered P(a-a)o2/Pao2, and increased
      Pao2/Fio2. Correlations between plasma concentrations of 6-keto-prostaglandin
      F1alpha or thromboxane B2 and measures of respiratory performance could be shown
      during rapid and slow fat infusion, respectively. In the sepsis group, the P/T
      ratio remained unchanged at either infusion rate, but pulmonary shunt fraction
      and P(a-a)o2/Pao2 decreased after rapid fat infusion, whereas Pao2/Fio2
      increased. CONCLUSION: Pulmonary hemodynamics and gas exchange are related to
      changes of arterial prostanoid levels in ARDS patients, depending on the rate of
      fat infusion. In ARDS but not in sepsis patients clear of pulmonary organ
      failure, a changing balance of prostaglandin I2 and thromboxane A2 may modulate
      gas exchange, presumably via interference with hypoxic pulmonary
      vasoconstriction.

PMID- 11505130
TI  - Iontophoretic delivery of calcium for experimental hydrofluoric acid burns.
AB  - OBJECTIVE: To examine the efficacy of iontophoretic delivery of calcium to
      experimental hydrofluoric acid burns. DESIGN: Prospective, controlled study.
      SETTING: Institutional laboratory. SUBJECTS: Male nude rats. INTERVENTIONS: For
      the in vitro experiment, a full-thickness skin from the back was set in a
      vertical flow-through diffusion cell. Calcium chloride was applied to the donor
      chamber, and transdermal transport of calcium was examined with or without a
      voltage gradient of 1.5 V. Either intact skin or skin whose stratum corneum was
      stripped with adhesive tapes was used. For the in vivo experiment, hydrofluoric
      acid burns were induced by dispensing 50% hydrofluoric acid (50 microL) on the
      backs of the nude rats, who were under pentobarbital anesthesia. Rats were
      divided into four groups (n = 5 for each group): control group (burned but not
      treated); topical group (treated with calcium gluconate jelly); infiltration
      group (intradermal and subcutaneous injection of calcium gluconate); and
      iontophoresis group (treated with iontophoresis of calcium chloride at 1.5 V).
      Burn areas were measured and pathologic findings were classified microscopically
      into five stages at 1 wk: stage 1, epidermal burn; stage 2, superficial dermal
      burn; stage 3, deep dermal burn; stage 4, full-thickness burn; and stage 5, burn
      affecting the skeletal muscle. MEASUREMENTS AND MAIN RESULTS: In the in vitro
      experiment, calcium concentrations increased significantly only in stripped skins
      with a 1.5-V gradient. In the in vitro experiment, burn areas were reduced
      significantly in the iontophoresis group compared with the other three groups.
      Pathologic findings were significantly improved in the iontophoresis group
      compared with the control group. This efficacy of iontophoresis was observed when
      it was initiated within 30 mins after hydrofluoric acid burn. CONCLUSIONS: These
      results show that transdermal transport of calcium was enhanced in stripped skins
      by iontophoresis and that iontophoresis was more efficacious than topical or
      infiltration therapy for experimental hydrofluoric acid burns. Iontophoretic
      delivery of calcium seems to be easier than intra-arterial infusion and may be
      effective for the lesions where intra-arterial infusion is difficult.

PMID- 11505131
TI  - Repetitive high-pressure recruitment maneuvers required to maximally recruit lung
      in a sheep model of acute respiratory distress syndrome.
AB  - OBJECTIVE: To compare the effects of two different recruitment maneuvers repeated
      multiple times on gas exchange lung injury, hemodynamic, and lung mechanics.
      DESIGN: Randomized prospective comparison. SETTINGS: Animal research laboratory.
      SUBJECT: Nineteen fasted Hampshire sheep. INTERVENTIONS: In 15 27-kg sheep with
      saline lavage lung injury, we compared the effects of two recruitment maneuvers:
      40 cm H2O continuous positive airway pressure for 60 secs and 40 cm H2O positive
      end-expiratory pressure with 20 cm H2O pressure control, rate 10 breaths/min,
      inspiratory to expiratory ratio 1:1 for 2 mins. Each recruitment maneuver was
      repeated four times, every 30 mins after a 30-sec ventilator disconnection. An
      additional group received no recruitment maneuvers. Animals were assigned
      randomly to the three groups and ventilated with 20 cm H2O positive end
      expiratory pressure, pressure control 15 cm H2O, rate 20 breaths/min, inspiratory
      to expiratory ratio 1:1, and Fio2 1.0 between recruitment maneuver periods.
      MEASUREMENTS AND MAIN RESULTS: Significant and marked increases in Pao2 were
      observed in the pressure control recruitment maneuver group but only after the
      second recruitment maneuver. In both the control group and continuous positive
      airway pressure groups, Pao2 did not significantly increase after any recruitment
      maneuver compared with baseline injury. There was a significant decrease in
      cardiac output immediately after some continuous positive airway pressure
      recruitment maneuvers and a significant increase in mean pulmonary artery
      pressure in both continuous positive airway pressure and pressure control groups
      immediately after recruitment maneuvers, but these changes resolved within 10
      mins. There were no marked histologic differences between groups and no
      volutrauma. CONCLUSION: In this model, maximal lung recruitment was obtained with
      40 cm H2O positive end-expiratory pressure and 20 cm H2O pressure control applied
      repetitively every 30 mins for 2 mins without physiologic or histologic harm.
      Multiple recruitment maneuvers in some animals were required for maximum effect.

PMID- 11505132
TI  - Comparison of epinephrine with vasopressin on bone marrow blood flow in an animal
      model of hypovolemic shock and subsequent cardiac arrest.
AB  - OBJECTIVE: The intraosseous route is an emergency alternative for the
      administration of drugs and fluids if vascular access cannot be established.
      However, in hemorrhagic shock or after vasopressors are given during
      resuscitation, bone marrow blood flow may be decreased, thus impairing absorption
      of intraosseously administered drugs. In this study, we evaluated the effects of
      vasopressin vs. high-dose epinephrine in hemorrhagic shock and cardiac arrest on
      bone marrow blood flow. DESIGN: Prospective, randomized laboratory investigation
      that used an established porcine model for measurement of hemodynamic variables
      and organ blood flow. SETTING: University hospital laboratory. SUBJECTS: Fourteen
      pigs weighing 30 +/- 3 kg. INTERVENTIONS: Radiolabeled microspheres were injected
      to measure bone marrow blood flow during a prearrest control period and during
      hypovolemic shock produced by rapid hemorrhage of 35% of the estimated blood
      volume. In the second part of the study, ventricular fibrillation was induced;
      after 4 mins of untreated cardiac arrest and 4 mins of standard cardiopulmonary
      resuscitation, a bolus dose of either 200 microg/kg epinephrine (n = 6) or 0.8
      units/kg vasopressin (n = 6) was administered. Defibrillation was attempted 2.5
      mins after drug administration, and blood flow was assessed again at 5 and 30
      mins after successful resuscitation. MEASUREMENTS AND MAIN RESULTS: Mean +/- sem
      bone marrow blood flow decreased significantly during induction of hemorrhagic
      shock from 14.4 +/- 4.1 to 3.7 +/- 1.8 mL.100 g-1.min-1 in the vasopressin group
      and from 18.2 +/- 4.0 to 5.2 +/- 1.0 mL.100 g-1.min-1 in the epinephrine group (p
      =.025 in both groups). Five minutes after return of spontaneous circulation, mean
      +/- sem bone marrow blood flow was 3.4 +/- 1.1 mL.100 g-1.min-1 after vasopressin
      and 0.1 +/- 0.03 mL.100 g-1.min-1 after epinephrine (p =.004 for vasopressin vs.
      epinephrine). At the same time, bone vascular resistance was significantly (p
      =.004) higher in the epinephrine group when compared with vasopressin (1455 +/-
      392 vs. 43 +/- 19 mm Hg. mL-1.100 g.min, respectively). CONCLUSIONS: Bone blood
      flow responds actively to both the physiologic stress response of hemorrhagic
      shock and vasopressors given during resuscitation after hypovolemic cardiac
      arrest. In this regard, bone marrow blood flow after successful resuscitation was
      nearly absent after high-dose epinephrine but was maintained after high-dose
      vasopressin. These findings emphasize the need for pressurized intraosseous
      infusion techniques, because bone marrow blood flow may not be predictable during
      hemorrhagic shock and drug therapy.

PMID- 11505134
TI  - Relative roles of vascular and airspace pressures in ventilator-induced lung
      injury.
AB  - OBJECTIVE: To determine whether elevations in pulmonary vascular pressure induced
      by mechanical ventilation are more injurious than elevations of pulmonary
      vascular pressure of similar magnitude occurring in the absence of mechanical
      ventilation. DESIGN: Prospective comparative laboratory investigation. SETTING:
      University research laboratory. SUBJECTS: Male New Zealand white rabbits.
      INTERVENTIONS: Three groups of isolated, perfused rabbit lungs were exposed to
      cyclic elevation of pulmonary artery pressures arising from either intermittent
      positive pressure mechanical ventilation or from pulsatile perfusion of lungs
      held motionless by continuous positive airway pressure. Peak, mean, and nadir
      pulmonary artery pressures and mean airway pressure were matched between groups
      (35, 27.4 +/- 0.74, and 20.8 +/- 1.5 mm Hg, and 17.7 +/- 0.22 cm H2O,
      respectively). MEASUREMENTS AND MAIN RESULTS: Lungs exposed to elevated pulmonary
      artery pressures attributable to intermittent positive pressure mechanical
      ventilation formed more edema (6.8 +/- 1.3 vs. 1.1 +/- 0.9 g/g of lung),
      displayed more perivascular (61 +/- 26 vs. 15 +/- 13 vessels) and alveolar
      hemorrhage (76 +/- 11% vs. 26 +/- 18% of alveoli), and underwent larger
      fractional declines in static compliance (88 +/- 4.4% vs. 48 +/- 25.1% decline)
      than lungs exposed to similar peak and mean pulmonary artery pressures in the
      absence of tidal positive pressure ventilation. CONCLUSIONS: Isolated phasic
      elevations of pulmonary artery pressure may cause less damage than those
      occurring during intermittent positive pressure mechanical ventilation,
      suggesting that cyclic changes in perivascular pressure surrounding extra
      alveolar vessels may be important in the genesis of ventilator-induced lung
      injury.

PMID- 11505136
TI  - The selective guanylate cyclase inhibitor ODQ reduces multiple organ injury in
      rodent models of Gram-positive and Gram-negative shock.
AB  - OBJECTIVE: An enhanced formation of endogenous nitric oxide contributes to the
      circulatory failure caused by endotoxin (lipopolysaccharide). Many of the
      biological actions of nitric oxide are mediated by the guanylate cyclase/cyclic
      guanosine 3prime;,5'-monophosphate system. We recently discovered that two cell
      wall components, namely lipoteichoic acid and peptidoglycan of the Gram-positive
      bacterium Staphylococcus aureus, synergize to cause shock and multiple organ
      dysfunction syndrome in the rat. Here we investigate the effects of a selective
      guanylate cyclase inhibitor, 1H-(1,2,4)oxadiazole(4,3-alpha)quinoxaline-1-one
      (ODQ), on the circulatory failure and multiple organ dysfunction syndrome
      (kidney, liver, lung) caused by a) coadministration of lipoteichoic acid and
      peptidoglycan (Gram-positive shock) or b) lipopolysaccharide (Gram-negative
      shock) in the anesthetized rat. Furthermore, we investigated whether ODQ
      scavenges superoxide anions and/or hydroxyl radicals. DESIGN: The in vivo portion
      of the study was a prospective, randomized, controlled animal study. The in vitro
      portion included a) cultured ventricular myoblasts of the rat, H9c2(2-1) cells,
      and b) a cell free superoxide anion assay system. SETTING: University-based
      research laboratory. SUBJECTS: Seventy-five anesthetized, male Wistar rats were
      used for the in vivo study. INTERVENTIONS: For the in vivo portion of the study,
      after surgical preparation, anesthetized rats were observed for 6 hrs. All rats
      were pretreated and received an intravenous infusion of saline (1.5 mL.kg-1.hr
      1), which was maintained throughout the experiment. The rats were assigned to
      nine groups. Group 1 contained control rats (sham) subjected to 2 mL/kg saline
      intraperitoneally, 2 hrs before the experiment (n = 7). Group 2 contained control
      rats (sham) that received 2 mg/kg ODQ intraperitoneally, 2 hrs before the
      experiment (n = 9). Group 3 contained control rats (sham) that received 2 mL/kg
      dimethyl sulfoxide, 30% v/v in saline intraperitoneally, as a vehicle for ODQ, 2
      hrs before the experiment (n = 6). In group 4 rats, Gram-positive shock was
      induced by coadministration of lipoteichoic acid (3 mg/kg intravenously) and
      peptidoglycan (10 mg/kg intravenously) (n = 10). In group 5, rats were pretreated
      with ODQ (as described previously) before lipoteichoic acid/peptidoglycan (n =
      9). In group 6, rats were pretreated with dimethyl sulfoxide (as described
      previously) before lipoteichoic acid/peptidoglycan (n = 7). In group 7, Gram
      negative shock was induced by lipopolysaccharide (6 mg/kg intravenously) (n =
      11). In group 8, rats were pretreated with ODQ (as described previously) before
      lipopolysaccharide (n = 8). In group 9, rats were pretreated with dimethyl
      sulfoxide (as described previously) before lipopolysaccharide (n = 8). For the in
      vitro portion of the study, rat cells were preincubated with vehicle (saline
      and/or dimethyl sulfoxide) and ODQ (0.1 microM to 1 mM) for 2 hrs. The cells then
      were exposed to H2O2 (1 mM) for 4 hrs at 37 degrees C, after which time cell
      viability was determined by measuring the mitochondrial-dependent reduction of 3
      (4,5-di-methyliazol-2-yl)-2,5-diphenyltetrazolium bromide to blue formazan. Next,
      an aqueous solution was incubated with ODQ (as described previously), and
      superoxide anions were produced by using a hypoxanthine/xanthine-oxidase assay.
      The chemiluminescence assay was used to evaluate any potential antioxidative
      effects of ODQ. MEASUREMENTS AND MAIN RESULTS: In vivo, administration of
      lipoteichoic acid/peptidoglycan or lipopolysaccharide resulted within 6 hrs in
      hypotension, acute renal dysfunction, hepatocellular injury, and lung injury.
      Pretreatment of rats with ODQ attenuated the renal dysfunction, lung injury, and
      hepatocellular injury caused by lipoteichoic acid/peptidoglycan or
      lipopolysaccharide. In vitro, administration of H2O2 (for 4 hrs) to rat
      cardiomyoblasts decreased mitochondrial respiration attributable to generation of
      hydroxyl radicals. Pretreatment of cells with ODQ did not abolish this cell
      injury. In addition, ODQ did not scavenge superoxide anions. CONCLUSIONS: These
      results imply that ODQ, an inhibitor of guanylate cyclase, reduces the multiple
      organ injury and dysfunction caused by wall fragments of Gram-positive or Gram
      negative bacteria in the anesthetized rat. The observed protective effects of ODQ
      are not attributable to the ability of ODQ to reduce the formation or the effects
      of superoxide anions or hydroxyl radicals.

PMID- 11505138
TI  - Hypoxia-hypotension decreases pressor responsiveness to exogenous catecholamines
      after severe traumatic brain injury in rats.
AB  - OBJECTIVE: To quantify the phenylephrine pressor responsiveness after severe
      brain injury combined with hypoxia-hypotension, and to study the respective roles
      of brain injury and hypoxia-hypotension in the observed alteration. DESIGN:
      Randomized study. SETTING: Accredited animal laboratory. SUBJECTS: Adult Sprague
      Dawley rats. INTERVENTIONS: Anesthetized animals were assigned to control, brain
      injury, hypoxia-hypotension, and brain injury combined with hypoxia-hypotension
      groups. Brain injury was induced with an impact-acceleration device. During the
      15-min hypoxia-hypotension, arterial oxygen pressure was decreased to 40 torr
      (5.3 kPa) and mean arterial pressure to 30 mm Hg. Thirty-six of the 53 included
      rats were alive at the end of hypoxia-hypotension (nine animals per group). In an
      additional group (Hypo, n = 8), mean arterial pressure was lowered to the level
      observed in brain injury combined with hypoxia-hypotension with pentobarbital
      infusion. Sixty minutes after injuries (T60), animals received 0.1, 1, and 10
      microg/kg phenylephrine in a random order. Pressor responsiveness to
      phenylephrine was defined as maximal postinjection minus preinjection mean
      arterial pressure. MEASUREMENTS AND MAIN RESULTS: During hypoxia-hypotension,
      mortality was higher and residual restored blood volume was lower (p <.01) in the
      animals with brain injury and hypoxia-hypotension compared with hypoxia
      hypotension alone. At T60, mean arterial pressure (mm Hg) was lower (p <.01) in
      the brain injury group (83 +/- 22) compared with controls (110 +/- 10) and in
      brain injury combined with hypoxia-hypotension (76 +/- 18) compared with controls
      and hypoxia-hypotension (107 +/- 14). Pressor responsiveness (mm Hg) to 1 and 10
      microg/kg phenylephrine was less (p <.05) in brain injury combined with hypoxia
      hypotension (15 +/- 6 and 44 +/- 8) and hypoxia-hypotension (15 +/- 3 and 44 +/-
      8) compared with controls (26 +/- 2 and 57 +/- 11). No significant difference was
      observed for phenylephrine pressor responsiveness between controls and the Hypo
      group (25 +/- 5 and 66 +/- 7). CONCLUSIONS: Combination of brain injury and
      hypoxia-hypotension induces a severe hemodynamic alteration associated with a
      decreased pressor responsiveness to phenylephrine. Transient hypoxia-hypotension
      is responsible for the depressed alpha-1 adrenergic reactivity.

PMID- 11505140
TI  - Endothelin-1 blockade corrects mesenteric hypoperfusion in a porcine low cardiac
      output model.
AB  - OBJECTIVE: To study the importance of endothelin-1-induced vasoconstriction in a
      model of acute and maintained low cardiac output, by investigating regional
      changes within the mesenteric and particularly the intestinal mucosal
      circulation. DESIGN: Prospective, controlled animal study. SETTING: University
      affiliated research laboratory. SUBJECTS: Thirteen fasted, anesthetized,
      mechanically ventilated landrace pigs. MEASUREMENTS AND MAIN RESULTS: Cardiac
      output, portal venous blood flow, renal arterial flow, jejunal mucosal
      microcirculation by laser Doppler flowmetry, jejunal capnotonometry (Pco2 gap),
      and jejunal mucosal oxygenation (tPo2) were monitored. Cardiac tamponade was
      established to reduce portal venous blood flow to a preset end point at two
      thirds of baseline. Measurements were made at baseline, after 90 mins of cardiac
      tamponade, and 90 mins after the administration of the combined
      endothelinA/endothelinB antagonist tezosentan at 1 mg.kg-1.hr-1 during tamponade
      in seven animals. Six animals served as time controls and received only the
      vehicle. Cardiac tamponade decreased portal venous blood flow, renal arterial
      flow, and laser Doppler flowmetry, whereas the Pco2 gap increased. The change in
      tPo2 failed to gain statistical significance (p =.08). Administration of
      tezosentan during tamponade restored portal venous blood flow and laser Doppler
      flowmetry to baseline values, increased tPo2 above baseline, and decreased Pco2
      gap. No effect on renal arterial flow was observed. Investigated variables
      remained unchanged in control animals after induction of cardiac tamponade.
      CONCLUSIONS: Endothelin-1 blockade in acute cardiac failure improves mesenteric,
      but not renal, perfusion, illustrating the regional importance of endothelin-1
      induced vasoconstriction. Importantly, endothelin-1 blockade restored mucosal
      blood flow and oxygenation, which might be particularly interesting considering
      the implications for maintenance of mucosal barrier integrity in low output
      states.

PMID- 11505142
TI  - Activation of alveolar macrophages in acid-injured lung in rats: different
      effects of pentoxifylline on tumor necrosis factor-alpha and nitric oxide
      production.
AB  - OBJECTIVE: To determine whether acid instillation augments tumor necrosis factor
      alpha and nitric oxide production by alveolar macrophages in rats, and to study
      the effects of treatment with pentoxifylline before acid instillation on the
      production of these inflammatory mediators. DESIGN: Controlled laboratory
      investigation on tumor necrosis factor-alpha and nitric oxide production by
      alveolar macrophages of rats that had acid-induced lung injury. SETTING:
      University research laboratory. SUBJECT: Alveolar macrophages of rats.
      INTERVENTIONS: Alveolar macrophages were recovered by bronchoalveolar lavage at
      4, 10, 16, 24, and 72 hrs after unilateral hydrochloric acid (pH, 1.0; volume,
      0.1 mL) instillation into the lungs of rats. Alveolar macrophages then were
      cultured with or without lipopolysaccharide. One group of rats was pretreated
      with pentoxifylline before acid instillation. MEASUREMENTS AND MAIN RESULTS:
      Alveolar macrophages from both acid-instilled and contralateral lungs, which had
      recovered 24 hrs after acid instillation, produced significantly greater tumor
      necrosis factor-alpha and nitric oxide. Subsequent exposure to
      lipopolysaccharide, as a surrogate for bacterial infection, further promoted
      tumor necrosis factor-alpha and nitric oxide release. Alveolar macrophages from
      rats pretreated with pentoxifylline before acid instillation produced
      significantly less tumor necrosis factor-alpha and did not overproduce tumor
      necrosis factor-alpha when exposed to lipopolysaccharide. In contrast,
      pretreatment with pentoxifylline had no effect on nitric oxide production by
      alveolar macrophages. CONCLUSIONS: Acid instillation stimulates alveolar
      macrophages to produce tumor necrosis factor-alpha and nitric oxide.
      Pentoxifylline preserved innate production of tumor necrosis factor-alpha to
      lipopolysaccharide and did not inhibit the production of bactericidal nitric
      oxide. This may partly explain why pentoxifylline reduces acid aspiration-induced
      lung injury while maintaining the host's ability to combat bacterial infection
      after acid aspiration.

PMID- 11505143
TI  - Glomerular permeability after surgical trauma in children: relationship between
      microalbuminuria and surgical stress score.
AB  - OBJECTIVES: To determine whether there is an increase of urinary albumin during
      and after surgical trauma and investigate a possible relationship between
      microalbuminuria and the severity of surgical stress. DESIGN: Prospective study.
      SETTING: University hospital pediatric intensive care unit. PATIENTS: Forty
      consecutive children scheduled for elective surgery. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: Microalbuminuria/urinary creatinine ratio (MACR)
      was measured before, during, and after elective moderate or major surgical
      procedures. The Oxford Surgical Stress Score (SSS) was determined for each
      patient at the end of the operation, and its relationship with maximum deviation
      of MACR from baseline values was investigated. MACR showed a progressive increase
      during surgery and a decrease afterward, reaching preoperative values in most
      cases within 24 hrs after the end of surgery. There was a significant correlation
      between the increase in MACR and severity of the surgical trauma as measured by
      SSS. Two patients showed a rise in MACR after the initial postoperative
      normalization before clinical appearance of a surgical complication and one
      patient showed a persistent rise in MACR before clinical appearance of a septic
      complication. None of the other patients showed any rise in MACR after
      postoperative normalization, and they all had an uneventful recovery.
      CONCLUSIONS: MACR rises during and after major or moderate elective surgery in
      children. There is a significant positive correlation between severity of
      surgical trauma and capillary permeability in pediatric patients.
      Microalbuminuria, as an index of capillary permeability, may be an early sign of
      incipient complications and assist in the identification of those patients whose
      condition will deteriorate. The test is a cheap, blood-sparing, easy-to-perform
      bedside procedure that may have a useful role in clinical practice for evaluating
      the effect of surgical trauma on capillary permeability in children.

PMID- 11505144
TI  - Credentialing for critical care in small hospitals.
AB  - OBJECTIVE: To assess credentialing practices for critical care admissions and
      procedures in smaller hospitals within the United States. METHODS: A
      questionnaire was sent to credentialing coordinators of 500 randomly selected
      American Hospital Association hospitals with fewer than 300 beds. MEASUREMENTS
      AND MAIN RESULTS: Most hospitals validate qualifications for intensive care unit
      (ICU) admitting and procedural privileges through recommendations only. Fewer
      (16%) require a specified prior number of procedures to have been performed, and
      9% require prospective supervision before privileges are granted. Critical care
      subspecialists are present in 57% of these hospitals and tend to be in the larger
      facilities with more critical care beds. Criteria for ICU admission and procedure
      privileges appear to be inclusive, because family medicine, obstetrics
      gynecology, orthopedic surgery, and neurology specialists are often credentialed.
      The presence of a critical care subspecialist is associated with fewer hospitals
      credentialing family medicine specialists for ICU admission and procedures but
      not obstetrician-gynecologists, orthopedic surgeons, or neurologists.
      CONCLUSIONS: This is a brief descriptive report of hospital policies that define
      which physicians are permitted to care for critically ill/injured patients in
      small U.S. hospitals. The presence of a critical care specialist appears to
      influence only slightly the ICU credentialing processes for other selected
      specialists.

PMID- 11505145
TI  - Enteral nutrition: how do we get more of the good and less of the bad and ugly?

PMID- 11505146
TI  - Assessment of intravascular volume: a comedy of errors.

PMID- 11505147
TI  - Gut protection: why and how?

PMID- 11505148
TI  - Low-dose dopamine in the intensive care unit: DNR or DNRx?

PMID- 11505149
TI  - Living, not existing, beyond critical care.

PMID- 11505150
TI  - Acute cor pulmonale in acute respiratory distress syndrome: a dreaded
      complication of the past?

PMID- 11505151
TI  - Serum cytokines, proteins, and receptors in acute pancreatitis: mediators,
      markers, or more of the same?

PMID- 11505152
TI  - Caution: use fat emulsions judiciously in intensive care patients.

PMID- 11505153
TI  - Electricity and the treatment of hydrofluoric acid burns--the wave of the future
      or a jolt from the past?

PMID- 11505154
TI  - Recruitment maneuvers to achieve an "open lung"--whether and how?

PMID- 11505155
TI  - Vasopressin in advanced cardiac life support?

PMID- 11505156
TI  - New drugs for the treatment of septic shock.

PMID- 11505158
TI  - Soluble L-selectin levels in experimental human endotoxemia.

PMID- 11505159
TI  - Meropenem and continuous renal replacement.

PMID- 11505160
TI  - Final version of the Critical Care Family Satisfaction Survey questionnaire.

PMID- 11505162
TI  - Environmental epidemiology: where we've been and where we're going.

PMID- 11505163
TI  - Additional insights into the etiology of cardiac anomalies.

PMID- 11505164
TI  - Congenital heart defects, maternal febrile illness, and multivitamin use: a
      population-based study.
AB  - We assessed the relation between febrile illness during pregnancy and cardiac
      defects in the offspring in a population-based case-control study in metropolitan
      Atlanta. Case infants (905) with cardiac defects were actively ascertained from
      multiple sources. Control infants (3,029) were infants without birth defects who
      were selected from birth certificates by stratified random sampling. We compared
      those whose mothers reported febrile illness from 1 month before pregnancy
      through the third month of pregnancy with those whose mothers reported no illness
      during the same period. Febrile illness was positively associated with the
      occurrence of heart defects in the offspring (odds ratio [OR] = 1.8; 95%
      confidence interval = 1.4-2.4). When influenzalike illness was the reported
      febrile illness, the OR was 2.1 (95% confidence interval = 0.8-5.5). The
      association with febrile illness was strongest for tricuspid atresia (OR = 5.2),
      left obstructive defects (OR = 2.7), transposition of the great arteries (OR =
      1.9), and ventricular septal defects (OR = 1.8). These ORs were generally lower
      among mothers who used multivitamins during the periconceptional period.

PMID- 11505165
TI  - Vitamin A and cardiac outflow tract defects.
AB  - To assess the relationship between maternal intake of vitamin A and cardiac
      outflow tract defects, we examined data from a population-based case-control
      study among liveborn infants born from 1987 through 1989 to mothers residing in
      the Baltimore-Washington area. Case infants (126) had a nonsyndromic cardiac
      outflow tract defect. Control infants (679) did not have birth defects and were a
      stratified random sample of liveborn infants from the same area. The main
      exposure was average daily maternal intake of retinol and provitamin A
      carotenoids from foods and supplements during the year before conception.
      Compared with an average intake of less than 10,000 IU, retinol intake of 10,000
      IU or more from supplements was associated with a ninefold increased risk for
      transposition of the great arteries (odds ratio = 9.2; 95% confidence interval =
      4.0-21.2), but not for outflow tract defects with normally related arteries (odds
      ratio = 0.8; 95% confidence interval = 0.1-6.6). Similar intakes of carotenoids
      and dietary retinol were not associated with an increased risk for either type of
      outflow tract defect.

PMID- 11505166
TI  - Do pregnant women report use of dispensed medications?
AB  - Surveillance of drug safety in pregnancy often draws on administrative
      prescription registries. Noncompliance in the use of prescribed medication may be
      frequent among pregnant women owing to their fear of fetotoxic side effects. To
      estimate compliance in the use of prescription drugs dispensed during pregnancy,
      we compared prescription data from the North Jutland Prescription Database with
      information on drug use provided by pregnant women to the Danish National Birth
      Cohort (DNBC), which is a health interview survey. We used the North Jutland
      Prescription Database to identify all prescription drugs dispensed during
      pregnancy for the 2,041 women who were enrolled in the DNBC in the County of
      North Jutland, Denmark. Compliance was defined as the probability of reporting
      drug use in DNBC after purchasing a dispensed prescription drug. The overall
      compliance to drugs purchased within 120 days before the interview was 43% (95%
      confidence interval = 40-46). Drugs used for treating chronic diseases, for
      example, beta-blockers, insulin, thyroid hormones, and diuretic and antiepileptic
      drugs, were always reported to be used, but compliance was low for drugs used for
      local or short-term treatment such as antihistamines, antibiotics, antacids,
      nonsteroid anti-inflammatory drugs, and gynecologic drugs. Thus, for the latter
      drug groups the prescription database may provide an incomplete identification of
      exposure. Neither data source is unbiased regarding actual drug intake.
      Nevertheless, our results indicate that for some drug groups risk assessment
      studies based on prescription data may produce false negative results as a result
      of noncompliance.

PMID- 11505167
TI  - Smoking, genetic polymorphisms in biotransformation enzymes, and nonsyndromic
      oral clefting: a gene-environment interaction.
AB  - The importance of maternal smoking in the pathogenesis of oral facial clefts is
      not clear. Susceptibility to cigarette smoke depends on biotransformation of the
      toxic compounds by mother and embryo. In a population-based case-control study,
      we investigated the effects of maternal smoking during the first pregnancy
      trimester and the interaction with polymorphisms in the biotransformation enzymes
      cytochrome P450 1A1 (CYP1A1) and glutathione S-transferase theta 1-1 (GSTT1) on
      the risk of nonsyndromic oral clefting in the offspring. We recruited 113 infants
      with nonsyndromic oral clefts and their mothers, as well as 104 control infants
      and their mothers. Maternal smoking habits were collected regarding the period 3
      months before through 3 months after conception. Buccal swabs were taken from
      mothers and infants for genetic analysis. Maternal smoking was not strongly
      associated with oral clefting (odds ratio = 1.1; 95% confidence interval = 0.6
      2.2), nor were CYP1A1 and GSTT1 polymorphisms. Mothers who smoked and carried the
      GSTT1-null genotype, however, had an increased risk for having a child with oral
      clefting compared with nonsmokers with the wild type genotype (odds ratio = 3.2;
      95% confidence interval = 0.9-11.6). The risk was almost five times greater (odds
      ratio = 4.9; 95% confidence interval = 0.7-36.9) in mothers and infants both
      having the GSTT1-null genotype compared with both having the wild genotype. There
      was no interaction between CYP1A1 and maternal smoking in relation to oral
      clefting.

PMID- 11505168
TI  - Parental occupational exposures to electromagnetic fields and radiation and the
      incidence of neuroblastoma in offspring.
AB  - We examined parental occupational exposures to electromagnetic fields and
      radiation and the incidence of neuroblastoma in offspring. Cases were 538
      children diagnosed with neuroblastoma between 1992 and 1994 in the United States
      or Canada. Age-matched controls were selected by random-digit dialing.
      Occupational exposures to electrical equipment and radiation sources were
      classified by an industrial hygienist, and average exposures to extremely low
      frequency magnetic fields were estimated using a job exposure matrix. Maternal
      exposure to a broad grouping of sources that produce radiofrequency radiation was
      associated with an increased incidence of neuroblastoma (odds ratio = 2.8; 95%
      confidence interval = 0.9-8.7). Paternal exposure to battery-powered forklifts
      was positively associated with neuroblastoma (odds ratio = 1.6; 95% confidence
      interval = 0.8-3.2), as were some types of equipment that emit radiofrequency
      radiation (odds ratios congruent with 2.0); however, the broad groupings of
      sources that produce ELF fields, radiofrequency radiation, or ionizing radiation
      were not associated with neuroblastoma. Paternal average extremely low frequency
      magnetic field exposure >0.4 microTesla was weakly associated with neuroblastoma
      (odds ratio = 1.6; 95% confidence interval = 0.9-2.8), whereas maternal exposure
      was not. Overall, there was scant supportive evidence of strong associations
      between parental exposures in electromagnetic spectrum and neuroblastoma in
      offspring.

PMID- 11505170
TI  - Attributable fractions: bias from broad definition of exposure.
AB  - In certain special situations, simplification of an exposure measure into a
      dichotomy results in no bias from nondifferential misclassification when
      estimating the attributable fraction for "any exposure." This fact has led to
      recommendations to use a broad definition of exposure when estimating
      attributable fractions. I here review the assumptions underlying exposure
      simplification, focusing on the assumptions that the source and target
      populations have the same exposure distribution and that complete risk removal is
      possible. I argue that attributable fraction estimates based on dichotomization
      can be especially sensitive to violations of these assumptions, and hence
      misleading for projecting the impact of exposure reduction. I conclude that it is
      important to obtain and use detailed exposure and covariate information for
      attributable-fraction estimation.

PMID- 11505172
TI  - Socioeconomic status and mortality in Swedish women: opposing trends for
      cardiovascular disease and cancer.
AB  - We examined relations between socioeconomic status and cardiovascular disease,
      cancer, and diabetes mellitus in a 24-year prospective study of 1,462 Swedish
      women. Two socioeconomic indicators were used: the husband's occupational
      category for married women and a composite indicator combining women's
      educational level with household income for all women. The husband's occupational
      category was strongly associated with cardiovascular disease and cancer mortality
      in opposite directions, independent of age and other potential confounders. Women
      with husbands of lower occupational categories had an increased risk of
      cardiovascular disease mortality [relative risk (RR) = 1.60; 95% confidence
      interval (95% CI) = 1.09-2.33] while experiencing lower rates of all-site cancer
      mortality (RR = 0.69; 95% CI = 0.50-0.96). A similar relation was seen with the
      composite variable: women with low socioeconomic status had an increased risk of
      cardiovascular disease (RR = 1.37; 95% CI = 1.01-1.84) but a somewhat lower risk
      for cancer of all sites (RR = 0.86; 95% CI = 0.66-1.11). Finally, morbidity data
      (diabetes mellitus, stroke, and breast cancer) yielded results that were
      consistent with the mortality trends, and breast cancer appeared to account for a
      major part of the association between total cancer and high socioeconomic status.
      In summary, higher socioeconomic status was associated with decreased
      cardiovascular disease mortality and excess cancer mortality, in such a way that
      only a weak association was seen for all-cause mortality.

PMID- 11505171
TI  - Confounding and effect modification in the short-term effects of ambient
      particles on total mortality: results from 29 European cities within the APHEA2
      project.
AB  - We present the results of the Air Pollution and Health: A European Approach 2
      (APHEA2) project on short-term effects of ambient particles on mortality with
      emphasis on effect modification. We used daily measurements for particulate
      matter less than 10 microm in aerodynamic diameter (PM10) and/or black smoke from
      29 European cities. We considered confounding from other pollutants as well as
      meteorologic and chronologic variables. We investigated several variables
      describing the cities' pollution, climate, population, and geography as potential
      effect modifiers. For the individual city analysis, generalized additive models
      extending Poisson regression, using a smoother to control for seasonal patterns,
      were applied. To provide quantitative summaries of the results and explain
      remaining heterogeneity, we applied second-stage regression models. The estimated
      increase in the daily number of deaths for all ages for a 10 microg/m3 increase
      in daily PM10 or black smoke concentrations was 0.6% [95% confidence interval
      (CI) = 0.4-0.8%], whereas for the elderly it was slightly higher. We found
      important effect modification for several of the variables studied. Thus, in a
      city with low average NO2, the estimated increase in daily mortality for an
      increase of 10 microg/m3 in PM10 was 0.19 (95% CI = 0.00-0.41), whereas in a city
      with high average NO2 it was 0.80% (95% CI = 0.67-0.93%); in a relatively cold
      climate the corresponding effect was 0.29% (95% CI = 0.16-0.42), whereas in a
      warm climate it was 0.82% (95% CI = 0.69-0.96); in a city with low standardized
      mortality rate it was 0.80% (95% CI = 0.65-0.95%), and in one with a high rate it
      was 0.43% (95% CI = 0.24-0.62). Our results confirm those previously reported on
      the effects of ambient particles on mortality. Furthermore, they show that the
      heterogeneity found in the effect parameters among cities reflects real effect
      modification, which is explained by specific city characteristics.

PMID- 11505173
TI  - The influence on seeking care because of neck and shoulder disorders from work
      related exposures.
AB  - The aim of this study was to assess the influence of work-related physical and
      psychosocial factors on seeking care for neck or shoulder disorders among men and
      women in a general working population. The study population comprised gainfully
      employed (>17 hours per week) men and women in the municipality of Norrtalje,
      altogether 392 cases and 1,511 controls. Cases were defined as persons seeking
      care because of neck or shoulder disorders by any caregiver in the region. The
      study began in 1994 and continued to 1997. We assessed physical and psychosocial
      exposures by questionnaires and interviews. The pattern of seeking care for neck
      or shoulder disorders differed between men and women. Among men, work with
      vibrating tools [relative risk (RR) = 1.6], not having a fixed salary (RR = 1.9),
      and low demands in relation to competence (RR = 1.5) were the strongest risk
      indicators obtained in analyses stratified for age and previous symptoms. Among
      women, repetitive hand or finger movements (RR = 1.6), constrained sitting (RR =
      1.6), not having a fixed salary (RR = 2.0), and solitary work (RR = 1.8) were the
      strongest risk indicators. A large proportion of the general population was
      exposed to several of these moderately harmful conditions, and their concomitant
      effect may explain the high incidence of neck and shoulder disorders in the
      general working population.

PMID- 11505174
TI  - Joint effects of smoking and body mass index on prostate cancer risk.
AB  - Between 1979 and 1985, a population-based case-control study of cancer at
      multiple sites was carried out in Montreal. A total of 399 cases with
      histologically confirmed prostate cancer and 476 population controls, 45-70 years
      of age, gave face-to-face interviews and provided adequate smoking histories. We
      analyzed the effects of smoking cigarettes only and of smoking cigars, or pipes,
      or both, with or without cigarettes, on the risk of prostate cancer. Overall, the
      associations between smoking cigarettes and prostate cancer were weak and
      compatible with no effect; the associations with cigar and pipe smoking were
      stronger. Among men with high body mass index, however, we found appreciable
      associations between cigarette smoking and prostate cancer risk. A history of
      ever smoking daily was associated with an odds ratio of 2.31 (95% confidence
      interval = 1.09-4.89). Risk increased with the amount smoked per day and with the
      duration of smoking. Taken together, the findings of increased risk associated
      with cigar and pipe smoking and the findings of increased risk associated with
      cigarette smoking among obese men suggest that tobacco smoking may be a risk
      factor for prostate cancer.

PMID- 11505175
TI  - Occupational sunlight exposure and cancer incidence among Swedish construction
      workers.
AB  - We studied sunlight exposure from outdoor work in relation to cancer, using data
      from 323,860 men participating in an occupational health service program of the
      Swedish construction industry. An experienced industrial hygienist assessed the
      exposure for 200 job tasks. We estimated relative risks (RRs) adjusted for age,
      smoking, and magnetic field exposure. There was an increased RR in the high
      exposure group for myeloid leukemia [RR = 2.0, 95% confidence interval (95% CI) =
      1.1-3.6] and lymphocytic leukemia (RR = 1.7, 95% CI = 0.9-3.2). For non-Hodgkin's
      lymphoma there was a 30% increase in risk in the high-exposure group (95% CI =
      0.9-1.9). There was no increased risk of malignant melanoma, except for tumors of
      the head, face, and neck in the high-exposure group (RR = 2.0, 95% CI = 0.8-5.2),
      and we also found an increased risk for malignant melanoma of the eye in this
      group (RR = 3.4, 95% CI = 1.1-10.5). Outdoor workers had no increased risk of
      nonmelanoma skin cancer. Nevertheless, the RR for lip cancer (squamous cell
      carcinoma) among the high-exposure group was estimated at 1.8 (95% CI = 0.8-3.7).
      Among other sites, an increased risk of stomach cancer was suggested in this
      group (RR = 1.4, 95% CI = 1.0-1.9). The results for lymphoma, leukemia, and
      possibly also for stomach cancer might reflect a suppression of the immune system
      from ultraviolet light in outdoor workers.

PMID- 11505176
TI  - Environmental tobacco smoke and myocardial infarction among never-smokers in the
      Stockholm Heart Epidemiology Program (SHEEP).
AB  - An increased risk for myocardial infarction (MI) related to environmental tobacco
      smoke (ETS) exposure has previously been reported, but several aspects of the
      association are still uncertain. We studied the MI risk associated with ETS
      exposure among 334 nonfatal never-smoking MI cases and 677 population controls,
      45-70 years of age, in Stockholm County. A postal questionnaire with a telephone
      follow-up provided information on ETS exposure and other potential risk factors
      for MI. After adjustment for age, gender, hospital catchment area, body mass
      index, socioeconomic status, job strain, hypertension, diet, and diabetes
      mellitus, the odds ratio for MI was 1.58 (95% confidence interval = 0.97-2.56)
      for an average daily exposure of 20 cigarettes or more from the spouse. Combined
      exposure from spouse and work showed an increasing odds ratio for MI, up to 1.55
      (95% confidence interval = 1.02-2.34) in the highest category of weighted
      duration, that is, more than 90 "hour-years" of exposure (1 "hour-year" = 365
      hours, or 1 hour per day for 1 year). In addition, more recent exposure appeared
      to convey a higher risk. Our data confirm an increased risk of MI from exposure
      to ETS and suggest that intensity of spousal exposure, combined exposure from
      spouse and work, and time since last exposure are important.

PMID- 11505177
TI  - Lipid-lowering drugs and risk of myopathy: a population-based follow-up study.
AB  - We conducted a population-based cohort study to estimate the risk of myopathy
      associated with use of lipid-lowering drugs. Using data from general practices in
      the United Kingdom in 1991 through 1997, we identified three cohorts of
      individuals 40 to 74 years of age. One cohort comprised 17,219 persons who had
      received at least one prescription for lipid-lowering drugs in the period; a
      second cohort consisted of patients with a hyperlipidemia diagnosis who had not
      been prescribed lipid-lowering drugs (N = 28,974); and a third cohort comprised
      50,000 individuals from the general population with no diagnosis of
      hyperlipidemia. The incidence rate of myopathy in the cohort of users of lipid
      lowering drugs was 2.3 per 10,000 person-years [95% confidence interval (95% CI)
      = 1.2-4.4], which exceeded the incidence rates observed in the nontreated
      hyperlipidemia cohort [0 per 10,000 person-years (95% CI = 0.0-0.4)] and the
      general population [0.2 per 10,000 person-years (95% CI = 0.1-0.4)]. The relative
      risks of myopathy in current users of fibrates and statins compared with nonusers
      were 42.4 (95% CI = 11.6-170.5) and 7.6 (95% CI = 1.4-41.3), respectively.
      Potential risk factors other than drug use could not explain our findings in the
      nested case-control analysis. We conclude that use of lipid-lowering drugs is
      associated with a substantially greater risk of myopathy, which is most
      pronounced for fibrates. The absolute risk of myopathy in users of lipid-lowering
      drugs is, however, small.

PMID- 11505178
TI  - Relative risk of upper gastrointestinal complications among users of
      acetaminophen and nonsteroidal anti-inflammatory drugs.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) have been associated with an
      increase in upper gastrointestinal complications. There is no agreement, however,
      on whether all conventional NSAIDs have a similar relative risk (RR), and
      epidemiologic data are limited on acetaminophen. We studied the association
      between these medications and the risk of upper gastrointestinal
      bleed/perforation in a population-based cohort of 958,397 persons in the United
      Kingdom between 1993 and 1998. Our nested case-control analysis included 2,105
      cases and 11,500 controls. RR estimates were adjusted for several factors known
      to be associated with upper gastrointestinal bleed/perforation. Compared with non
      users, users of acetaminophen at doses less than 2 gm did not have an increased
      risk of upper gastrointestinal complications. The adjusted RR for acetaminophen
      at doses greater than 2 gm was 3.6 [95% confidence interval (95% CI) = 2.6-5.1].
      The corresponding RRs for low/medium and high doses of NSAIDs were 2.4 (95% CI =
      1.9-3.1) and 4.9 (95% CI = 4.1-5.8). The RR was 3.1 (95% CI = 2.5, 3.8) for short
      plasma half-life, 4.5 (95% CI = 3.5-5.9) for long half-life, and 5.4 (95% CI =
      4.0-7.1) for slow-release formulations of NSAIDs. After adjusting for daily dose,
      the differences in RR between individual NSAIDs tended to diminish except for
      apazone. Users of H2 receptor antagonists, omeprazole, and misoprostol had RRs of
      1.4 (95% CI = 1.2-1.8), 0.6 (95% CI = 0.4-0.9), and 0.6 (95% CI = 0.4-1.0),
      respectively. Among NSAID users, use of nitrates was associated with an RR of 0.6
      (95% CI = 0.4-1.0).

PMID- 11505179
TI  - Family history and the risk of early-onset persistent, early-onset transient, and
      late-onset asthma.
AB  - Family history of asthma and allergies strongly influences asthma risk in
      children, but the association may differ for early-onset persistent, early-onset
      transient, and late-onset asthma. We analyzed the relation between family history
      and these types of asthma using cross-sectional data from a school-based study of
      5,046 Southern California children. Parental and/or sibling history of asthma and
      allergy were generally more strongly associated with early-onset persistent
      asthma compared with early-onset transient or late-onset asthma. For children
      with two asthmatic parents relative to those with none, the prevalence ratio for
      early-onset persistent asthma was 12.1 [95% confidence interval (CI) = 7.91-18.7]
      compared with 7.51 (95% CI = 2.62-21.5) for early-onset transient asthma and 5.38
      (95% CI = 3.40-8.50) for late-onset asthma. Maternal smoking in pregnancy was
      predominantly related to the risk of early-onset persistent asthma in the
      presence of parental history of allergy and asthma, and the joint effects were
      more than additive (interaction contrast ratio = 3.10, 95% CI = 1.45-4.75). Our
      results confirm earlier data that parental history of asthma and allergy is most
      strongly associated with early-onset persistent asthma and suggest that among
      genetically predisposed children, an early-life environmental exposure, maternal
      smoking during pregnancy, favors the development of early-onset asthma that
      persists into later early childhood.

PMID- 11505181
TI  - Spreadsheet that shows P-value functions.

PMID- 11505180
TI  - Did medical research routinely exclude women? An examination of the evidence.

PMID- 11505182
TI  - Breast cancer among women who work at night.

PMID- 11505183
TI  - Does alcohol increase the risk of preterm delivery?

PMID- 11505184
TI  - Urban air pollution and lung cancer in Stockholm.

PMID- 11505186
TI  - Membership in Australasian Epidemiological Association.

PMID- 11505185
TI  - Congenital malformations and maternal exposure to glycol ethers in the Slovak
      Republic.

PMID- 11505187
TI  - Pesticides and fetal death due to congenital abnormalities.

PMID- 11505192
TI  - Part 1: Guidelines for the management of penetrating brain injury. Introduction
      and methodology.

PMID- 11505188
TI  - Pesticides and fetal death due to congenital anomalies: implications of an
      erratum.

PMID- 11505193
TI  - Neuroimaging in the management of penetrating brain injury.

PMID- 11505194
TI  - Intracranial pressure monitoring in the management of penetrating brain injury.

PMID- 11505195
TI  - Surgical management of penetrating brain injury.

PMID- 11505196
TI  - Vascular complications of penetrating brain injury.

PMID- 11505197
TI  - Management of cerebrospinal fluid leaks.

PMID- 11505198
TI  - Antibiotic prophylaxis for penetrating brain injury.

PMID- 11505199
TI  - Antiseizure prophylaxis for penetrating brain injury.

PMID- 11505200
TI  - Part 2: Prognosis in penetrating brain injury.

PMID- 11505201
TI  - Imaging tumour hypoxia: where are we?

PMID- 11505202
TI  - Whole-body (201)Tl scintigraphy can detect exercise lower limb perfusion
      abnormalities in asymptomatic diabetic patients with normal Doppler pressure
      indices.
AB  - Significant lower limb arterial obstruction is usually detected by Doppler ankle
      brachial pressure index (ABPI) measurement. However, ABPI is non-contributory in
      cases of diabetic medial sclerosis or calcifications and is unsuitable for the
      detection of small vessel involvement. Thallium-201, a perfusion agent, is
      frequently used for the investigation of coronary artery disease, and whole-body
      (201)Tl scintigraphy (WBS) has also been reported to be useful in the assessment
      of peripheral artery disease (PAD). Thus, we evaluated the clinical feasibility
      of simultaneous myocardial and lower limb perfusion assessment. WBS was performed
      after treadmill exercise and myocardial scintigraphy, and again 4 h later. Calf
      (201)Tl fractional activities (percentage of whole-body (201)Tl uptake) were
      calculated. We determined a threshold value of normal post-exercise calf (201)Tl
      uptake (mean of the (201)Tl fractional uptakes minus 2 SD) in a control group of
      nine healthy volunteers. We checked its accuracy in a pilot group of 25 diabetic
      patients with proven PAD. This method permitted the detection of lower limb
      perfusion abnormalities in 38% of 47 asymptomatic diabetic patients with no
      evidence of PAD. In conclusion, for asymptomatic diabetic patients, whole-body
      (201)Tl scintigraphy after a treadmill test seems an efficient method of showing
      lower limb perfusion abnormalities not detected by ABPI measurement. It allows
      the evaluation of vascular status with no additional inconvenience for patients
      when performed after myocardial scintigraphy.

PMID- 11505203
TI  - Quantification of limited augmentation of myocardial (99m)Tc-tetrofosmin uptake
      at exercise in stable coronary artery disease.
AB  - We evaluated the diagnostic accuracy of a new method for quantitative analysis of
      myocardial perfusion at exercise using (99m)Tc-tetrofosmin tomographic imaging.
      (99m)Tc-tetrofosmin imaging of an exercise-rest sequence was performed in 30
      patients with coronary artery disease (CAD) and eight age-matched control
      subjects. The exercise-induced myocardial count increase was calculated as the
      relative value (per cent increase ratio, %IR) to that at rest by correcting for
      physical decay for (99m)Tc and injected doses and by a subtraction technique.
      Exercise and rest (99m)Tc-tetrofosmin images were assessed visually and
      quantitatively using the per cent peak count and %IR of the myocardial count at
      exercise. Segments with significant coronary stenosis (diameter stenosis=75% or
      more) showed a significantly lower %IR than did those without significant
      coronary stenosis in the CAD patients (37+/-19% vs 63+/-21%, P<0.05). The
      diagnostic efficacy of visual analysis for detecting coronary stenosis was as
      follows: sensitivity, 58.1% and specificity, 81.4%. When %IR=37% was used for
      detecting significant coronary stenosis, sensitivity and specificity increased to
      74.2% and 93.2%, respectively. Furthermore, the quantitative analysis
      significantly (P=0.04) improved the overall diagnostic accuracy from 73.3% to
      86.7% compared to that of visual assessment. Thus, augmentation of myocardial
      (99m)Tc-tetrofosmin uptake at exercise is blunted in the myocardium with
      significant coronary stenosis. The calculation of myocardial count increase at
      exercise relative to that at rest can improve the diagnostic value of (99m)Tc
      tetrofosmin SPECT imaging and may contribute to more accurate quantification of
      myocardial ischaemia and impaired tracer uptake in coronary artery disease.

PMID- 11505204
TI  - FDG PET for evaluating the change of glucose metabolism in prostate cancer after
      androgen ablation.
AB  - In the clinical study of prostate cancer, the effect of androgen ablation on
      glucose metabolism in cancer tissue has not been elucidated. The purpose of this
      study was to investigate the change in glucose utilization due to endocrine
      therapy for prostate adenocarcinoma. Ten patients with histologically proven
      prostate cancer were prospectively investigated with (18)F-fluorodeoxyglucose and
      positron emission tomography (FDG PET) prior to and after the initiation of
      endocrine therapy. FDG uptake was calculated to measure glucose utilization in
      cancer tissue. The change in FDG accumulation was compared with changes in serum
      prostate specific antigen (PSA) level and prostate size. FDG accumulation in the
      prostate decreased in all patients 1-5 months after the initiation of hormone
      therapy. The serum PSA level and prostate size measured on computerized
      tomography (CT) also decreased in these periods. A decrease in FDG accumulation
      was also demonstrated in metastatic sites. In this study, there appeared to be a
      decrease in FDG uptake in prostate cancer after endocrine therapy not only in
      primary prostate cancer lesions but also at metastatic sites, suggesting that the
      glucose utilization by tumours was suppressed by androgen ablation.

PMID- 11505205
TI  - Captopril renography and the relevance of abnormal but bilateral identical curves
      in the diagnosis of renal artery stenosis.
AB  - BACKGROUND: Captopril renography (CR) has been shown to improve the effectiveness
      of renal scintigraphy in renovascular hypertension, by inhibiting angiotensin
      converting enzyme. CR is particularly sensitive and specific in unilateral renal
      artery stenosis (RAS), but results in patients with bilateral RAS are less
      favourable. The aim of this study was to investigate the meaning of abnormal but
      identical renographic curves in the diagnosis of RAS. PATIENTS AND METHODS: One
      hundred and fifty-eight patients clinically suspected for renovascular
      hypertension underwent CR, using 50 MBq (99)Tc(m)-mercaptoacetyltriglycine
      ((99)Tc(m)-MAG(3)), prior to performing renal angiography. CR was performed 1 h
      after captopril administration. Renograms were analysed according to the
      consensus criteria. All patients underwent angiography, considered as the "gold
      standard" in the detection of the presence of RAS (stenosis >50% was defined as
      significant). All kidneys were categorized into three groups, scintigraphically
      as well as angiographically: no stenosis, unilateral stenosis and bilateral
      stenosis. RESULTS: Out of 158 patients 100 (63%) showed a RAS on angiography (58
      (37%) unilateral, 42 (26%) bilateral). The sensitivity and specificity of CR
      evaluated by patient was 83% and 75%, respectively. Thirty patients with
      completely identical curves were identified, 21 patients with normal curves and
      nine patients with abnormal identical curves. All but one patient showed no RAS
      on the angiogram. In this single patient a unilateral stenosis was found.
      CONCLUSION: Identical curves on the renogram generally suggest no RAS and are
      probably due to intrinsic parenchymal disease.

PMID- 11505206
TI  - Validation of the preparation of individual doses of (131)I-sodium o
      iodohippurate ((131)I-hippuran).
AB  - The preparation of low activity doses of (131)I-hippuran has a drawback due to
      its high radioactivity concentration. In this study we diluted the
      radiopharmaceutical with saline or phosphate buffered saline (PBS) in order to
      decrease the radioactivity concentration, facilitate the preparation of
      individual doses and validate these procedures. We prepared doses of approx. 1.85
      MBq of (131)I-hippuran from 10 different batches the day before the calibration
      date: undiluted, and diluted 1:9 with saline or PBS. The radiochemical purity
      (RCP) was evaluated the day after the expiration date. The percentage of (131)I
      hippuran retained on syringes was assessed in vitro, after emptying the syringe
      and washing it twice with water (n=3 x 27); and in vivo, after the endovenous
      administration of the dose and washing the syringe twice with the patient's blood
      (n=3 x 75). Sterility was assessed using fluid thyoglicolate medium (n=3 x 15).
      All RCP values were greater than those required by the European Pharmacopoeia
      (>96%) except one of the undiluted (131)I-hippuran (95.8%) doses. No statistical
      difference was observed among them. The mean undiluted (131)I-hippuran retained
      in vitro was 5.4% (SD=6.5%), statistically greater (P<0.01) than both saline
      diluted (mean=1.5%, SD=1.1%) and PBS diluted (mean=2.0%, SD=2.4%). The mean
      undiluted (131)I-hippuran retained in vivo was 6.4% (SD=5.4%), statistically
      greater (P<10-5) than both saline diluted (mean=3.1%, SD=2.3%) and PBS diluted
      (mean=3.1%, SD=3.1%). We concluded that: (1) the dilution of (131)I-hippuran with
      saline or PBS makes both the preparation of individual doses and its
      administration to the patient easier without decreasing its radiopharmaceutical
      quality; and (2) using saline or PBS diluted (131)I-hippuran the percentage of
      radiopharmaceutical retained on the syringes, after use, is minimized.

PMID- 11505207
TI  - Studies on white blood cell labelling: (99)Tc(m)-HMPAO preferentially labels
      granulocytes.
AB  - Mixed leucocytes have been labelled in small volumes of plasma using small
      aliquots of hexamethylpropylene amine oxime (HMPAO) from vials of Ceretec, which
      were fractionated after reconstitution and stored frozen under nitrogen.
      Labelling efficiency was found to be independent of HMPAO concentration >8.8
      microg.ml-1 and independent of cell concentration at >8x10(7) ml-1. Results are
      presented from 145 patients referred for white cell scintigraphy. Labelling
      efficiency was 78.9+/-9.8%. The labelled mixed leucocytes were separated on a 3
      step density gradient of Percoll/plasma which showed that (99)Tc(m)-HMPAO gave a
      granulocyte/lymphocyte specific activity ratio of 1.67; the ratio for (111)In
      tropolone or oxine was 1.0, with no preference for granulocytes. It was noted
      that the labelling efficiency was reduced when there was a high proportion of
      lymphocytes present, and also that in one patient with non-Hodgkin's lymphoma the
      lymphocytes labelled as equally well as the granulocytes. The stability of the
      label was studied by fractionating the mixed cells after in vitro incubation and
      after 1 h in vivo; very little loss of label occurred.

PMID- 11505208
TI  - Quality of dynamic radionuclide renal imaging: multicentre evaluation using a
      functional renal phantom.
AB  - The aim of this study was to evaluate the quality of dynamic radionuclide renal
      imaging in Finland. Nineteen nuclear medicine departments participated. A
      functional renal phantom was imaged and interpreted as a patient-like study.
      Reconstruction and printouts were performed according to the clinical routine of
      each laboratory. Three nuclear medicine specialists anonymously evaluated the
      quality of the image sets. The visual scores of the experts were ranked from one
      to five. In addition, several numerical time-activity parameters were calculated
      and compared between the laboratories. The average visual scores of the experts
      for the image sets were 3.2+/-0.5 (range 2.4-4.2). Only two laboratories received
      a score value of 4 or higher. The average error for the time to reach maximum
      activity (T(max)) ranged from -29 to +18% and for the washout time to reach half
      activity from maximum activity (T(1/2)) ranged from -43 to +66%. These results
      suggest that the difference in calculated parameters between laboratories is most
      probably due to variations in study protocols and analysis programmes. The need
      for external quality assurance and quality improvement in nuclear renal imaging
      is evident and is recommended for regular use.

PMID- 11505209
TI  - (51)CrEDTA colonic permeability and therapy response in patients with ulcerative
      colitis.
AB  - Orally administered (51)Cr-labelled ethylenediaminetetraacetic acid ((51)CrEDTA)
      has been used to evaluate intestinal permeability in inflammatory bowel disease,
      especially Crohn's disease. However, information about colonic permeability in
      ulcerative colitis (UC) is relatively scarce. The aim of this study was to
      investigate the urinary excretion of orally administered (51)CrEDTA, its relation
      to disease activity and its response to medical therapy in patients with UC.
      Forty-three patients with UC and 19 controls were examined. Disease activity was
      evaluated by endoscopy. In 19 patients with active UC, the (51)CrEDTA
      permeability test was repeated after medical therapy. (51)CrEDTA (95 microCi; 26
      MBq) was given orally after an overnight fast and urine was collected over a 24 h
      period. The first urine samples were taken 5 h and the second 24 h after the oral
      administration of (51)CrEDTA. Urine samples were counted in a gamma counter. In
      controls, the median 5 h and 24 h excretions were 0.10% and 0.93%, respectively.
      Patients with UC showed significantly increased urine (51)CrEDTA excretion at
      both time intervals (5 h: 2.41%, P<0.0002; 24 h: 6.72%, P<0.0001). There was also
      a significant correlation between intestinal permeability and disease activity (5
      h: r=0.45, P=0.0025; 24 h: r=0.51 P=0.0006). After medical therapy, (51)CrEDTA
      urinary excretion was significantly decreased (pre-treatment UC: 7.87%; post
      treatment UC: 2.50%; P<0.0002). Briefly, the (51)CrEDTA test reflected colonic
      permeability in UC and might be useful as an indicator of disease severity.
      Moreover, this study suggested that, in patients with UC, medical therapy not
      only leads to the recovery of acute inflammation but also restores mucosal
      barrier integrity and function.

PMID- 11505211
TI  - Inhomogeneity of myocardial perfusion in heart transplant recipients: evaluation
      with dobutamine thallium-201 SPECT.
AB  - Progressive heterogeneity of thallium-201 single photon emission computed
      tomography (Tl-201 SPECT) in heart transplant recipients has been documented in
      Caucasians. However, in Chinese heart transplant recipients, a lower incidence of
      transplant coronary artery disease (CAD) has been noted than in Western
      transplant recipients. In this study, we examine whether heterogeneity of Tl-201
      SPECT exists in Chinese transplant recipients. Dobutamine Tl-201 SPECT was
      performed in 40 heart transplant recipients and the inhomogeneity scores were
      calculated. The difference between the scores of transplant recipients surviving
      less than 12 months and those of control subjects were not statistically
      significant. One year after transplantation, the inhomogeneity score increased
      progressively. The scores of transplant patients in the second and third years
      after transplant were similar to those of single-vessel CAD patients. Three years
      after transplant the scores were greatly increased. Thus, our data suggest that
      the progressive nature of graft vasculopathy also exists in Chinese heart
      transplant recipients. The progressive Tl-201 abnormalities may be one of the
      early signs of graft vasculopathy.

PMID- 11505210
TI  - (99m)Tc-E-selectin binding peptide for imaging acute osteomyelitis in a novel rat
      model.
AB  - INTRODUCTION: In the present study, (99m)Tc-radiolabelled E-selectin binding
      peptide ((99m)Tc-IMP-178) was investigated for its potential to image acute
      pyogenic osteomyelitis in a new animal model. Intraindividual comparisons were
      performed using an irrelevant peptide ((99m)Tc-IMP-100) to demonstrate
      specificity. METHODS: An acute pyogenic osteomyelitis was induced by injecting
      0.05 ml of 5% sodium morrhuate and 5x10(8) CFU of Staphylococcus aureus into the
      medullary cavity of the right tibia in 16 rats. Sixteen additional rats served as
      untreated controls. Whole-body imaging of pyogenic (n=4) and untreated (n=4)
      animals was performed continuously during the first 8 h (12 MBq i.v. of (99m)Tc
      IMP-178 and (99m)Tc-IMP-100 for control), and one further single image was
      acquired after 16 h p.i. Tissue biodistribution studies were performed in 12 rats
      with an acute pyogenic osteomyelitis and in 12 untreated rats 1, 4 and 24 h after
      injection. Data of the histological/radiological and haematological
      investigations were obtained in all animals. RESULTS: Histopathologically, 15 of
      16 treated rats (93%) developed an acute pyogenic osteomyelitis showing a major
      infiltration of the bone marrow by polymorphonuclear leukocytes as well as the
      formation of sequestra. Haematologically, the number of leukocytes increased by
      100%, the lymphocytes by 11% and the granulocytes decreased by 39%. After i.v.
      injection, (99m)Tc-IMP-178 rapidly cleared from the body resulting in good
      scintigraphic target-to-background (T/B) ratios. The highest uptake of the tracer
      in the pyogenic bone was observed at 60 min p.i. (0.43+/-0.02% ID.g-1 for (99m)Tc
      IMP-178 and 0.30+/-0.02% ID.g-1 for (99m)Tc-IMP-100), resulting in a higher
      osteomyelitis-to-healthy collateral ratio with T/B of 2.40+/-0.65 ((99m)Tc-IMP
      178) compared with 1.85+/-0.48 ((99m)Tc-IMP-100). No adverse reactions were seen
      after injection of (99m)Tc-IMP-178. CONCLUSIONS: (99m)Tc-IMP-178 allows imaging
      of an acute osteomyelitic lesions, presumably by interaction of (99m)Tc-IMP-178
      with activated upregulated vascular endothelium.

PMID- 11505212
TI  - Post-surgical ablation of thyroid remnants with high-dose (131)I in patients with
      differentiated thyroid carcinoma.
AB  - The aims of this study were to evaluate the efficacy of an empirically determined
      "fixed" high ablative dose of radioiodine ((131)I) therapy and to determine the
      utility of ultrasonography (US) in dose determination. A retrospective analysis
      was performed of 242 thyroid cancer cases treated with "fixed" high-dose (131)I
      for ablation of thyroid remnants without a pre-ablative (131)I diagnostic
      scintigraphy or radioiodine uptake study. Treatment doses ranged from 1850 MBq
      (50 mCi) to 7.4 GBq (200 mCi). The selection of the treatment dose was based on
      the surgical and pathological findings as well as the remnant thyroid volume
      calculated by US. A successful ablation was defined as the absence of activity in
      the thyroid bed on subsequent imaging studies. Successful ablation was obtained
      in 218 of the 242 patients (90%). In 162 of the 218 patients (74.3%), successful
      ablation was achieved after a single (131)I treatment. The remnant thyroid volume
      calculated by US was significantly different (P=0.04) between those who were
      successfully ablated and those who were not. The total (131)I dose needed for
      successful ablation was significantly higher in males (P=0.003). Patients with
      higher post-operative thyroglobulin (Tgb) levels and patients with a higher stage
      of disease required higher doses (P=0.036 and P=0.021 respectively). Serum Tgb
      levels were under 10 ng.ml(-1) in 220 of the 242 patients (90%) following
      radioiodine ablation while not receiving L-thyroxine suppression. Nineteen
      patients (7.8%) showed metastases on post-therapy scan and successful treatment
      was achieved in 11 of 19 (57.8%). Four of the 19 patients with distant metastases
      (revealed on post-treatment scan) were found to have been given a treatment dose
      of less than 200 mCi based on the proposed empirical approach. These results
      indicate that "fixed" high-dose (131)I treatment is clinically feasible with an
      acceptable dose underestimation rate, and the utilization of US in the
      determination of the thyroid remnant volume provides more accurate and
      reproducible results.

PMID- 11505213
TI  - Standard provocative manoeuvres in patients with and without left bundle branch
      block studied with myocardial SPECT.
AB  - BACKGROUND: The objective of this study was to determine the prevalence of
      anterior and septal defects in patients with left bundle branch block (LBBB), and
      to assess the diagnostic accuracy of myocardial single photon emission computed
      tomography (SPECT) with technetium compounds in patients with and without LBBB
      using standard provocative manoeuvres. METHODS: Five hundred and nine consecutive
      patients (456 without LBBB and 53 with LBBB) without previous infarction who had
      a coronary angiography performed within <3 months of the scintigraphic study were
      retrospectively evaluated. The same stress procedures were followed in all
      patients. (1) Only exercise when it was sufficient; and (2) exercise +
      simultaneous administration of dypiridamole if exercise was insufficient. Only
      reversible defects were considered positive and > or =50% of coronary stenosis
      was considered significant. RESULTS: Prevalence of reversible anterior and septal
      defects was low (33% and 12%, respectively) in patients with LBBB. Although lower
      values of global sensitivity (81%) and specificity (73%) were obtained in these
      patients, there were no significant differences with respect to the patients
      without LBBB (89% and 86%, respectively). Specificity values for the diagnosis of
      stenosis of left anterior descending (78%), left circumflex (96%) and right
      coronary artery (74%) in patients with LBBB were lower, but without significant
      statistical differences with respect patients without LBBB (90%, 96% and 82%,
      respectively). CONCLUSIONS: Myocardial SPECT with technetium compounds, using
      standard provocation manoeuvres, can be used in patients with LBBB with only a
      mild decrease in diagnostic accuracy as compared to patients without LBBB.

PMID- 11505214
TI  - Quantitative studies of bone using (18)F-fluoride and (99m)Tc-methylene
      diphosphonate: evaluation of renal and whole-blood kinetics.
AB  - We report a study of the renal and whole-blood kinetics of (18)F-fluoride and
      (99m)Tc-methylene diphosphonate ((99m)Tc-MDP) and their effect on the evaluation
      of the skeletal kinetics of the two bone tracers. Data were obtained during an
      investigation of postmenopausal women taking hormone replacement therapy who were
      compared with untreated, age-matched controls. After intravenous injection of 18F
      fluoride (1 MBq), (99m)Tc-MDP (1 MBq), (51)Cr-ethylenediaminetetraacetic acid
      (51Cr-EDTA) (3 MBq) and (125)I-human serum albumin ((125)I-HSA) (0.25 MBq),
      multiple blood samples and urine collections were taken between 0 and 4 h after
      injection. (51)Cr-EDTA data were used to evaluate the glomerular filtration rate
      (GFR) and the completeness of each timed urine collection. (125)I-HSA data were
      used to evaluate the plasma volume and the red cell uptake of the other three
      tracers. At 4 h, the cumulative urine excretions (and standard deviations, SDs)
      were: (99m)Tc-MDP, 58.2% (4.8%); (18)F-fluoride, 36.1% (5.7%); (51)Cr-EDTA, 81.5%
      (4.5%). Plots of the renal clearance of (18)F-fluoride against urine volume
      showed that urine flow rates greater than 5 ml.min-1 were necessary to ensure a
      constant renal clearance of (18)F and hence stable conditions for the evaluation
      of bone tracer kinetics. In contrast, a low urine flow rate had no effect on the
      renal kinetics of (99m)Tc-MDP. For MDP, the evaluation of skeletal kinetics
      requires data on protein binding so that calculations can be performed for free
      MDP. In the present study, protein binding of MDP was evaluated from the ratio of
      total (99m)Tc-MDP renal clearance to GFR based on the principle that free (99m)Tc
      MDP is a GFR tracer. Between 0 and 4 h after injection, the fractional protein
      binding of MDP increased linearly with time, changing from 21+/-5% immediately
      after injection to 58+/-5% at 4 h. Although red cell uptake of (99m)Tc-MDP was
      negligible, for (18)F-fluoride around 30% of circulating tracer was transported
      in red cells. In view of the data showing the rapid transport of (18)F-fluoride
      across the red cell membrane, bone kinetic data for (18)F are more accurately
      reported as whole-blood clearance rather than plasma clearance.

PMID- 11505215
TI  - Scintimammography: better detection of small-sized lesions with tomoscintigraphic
      than planar images, a phantom study.
AB  - Planar (99)Tc(m)-methoxyisobutylisonitrile ((99)Tc(m)-MIBI) scintimammography has
      been used for several years to detect breast cancer tumours, but with low
      sensitivity for small lesions. Results of tomoscintimammography studies have not
      been conclusive. We conducted a phantom study to compare the detection of small
      sized tumours with planar versus tomoscintigraphic images. We used a data
      spectrum anthropomorphic fillable breast phantom with two 9.8 mm and 12.4 mm
      spheres superficially or deep in the breast compartment with sphere/breast
      activity ratios varying from 3 to 6. We acquired planar and 180 degrees
      tomoscintigraphic images in each configuration using a double head standard gamma
      camera. In certain cases we varied different parameters (64x64 matrix or 360
      degrees rotation) in a second series of tomoscintigraphic acquisitions. We
      simultaneously used filtered back-projection reconstruction (FBP) and iterative
      reconstruction (IR). Planar images were shown by the sphere in 10 out of 25
      cases. Tomoscintigraphic images were shown by the sphere in nine out of 25 cases
      with FBP and in 18 out of 25 with IR. There was a significant difference between
      IR and FBP (P<0.01) and between planar and IR images (P<0.01), but no significant
      difference between planar and IR images. The noise/signal ratio was lower with
      planar images than with the two types of reconstruction (P<0.05) but was not
      significantly different between the two types of reconstruction. Contrast was
      lower on planar images than on the two types of reconstruction (P<0.05) and was
      also better on IR than on FBP images (P<0.05). Granularity was lower for planar
      images than for reconstruction images (P<0.01) and also lower for IR than for FBP
      (P<0.01). The tomoscintigraphic reconstructions acquired with a 64x64 matrix were
      only positive in four out of 10 cases, while they were positive in nine out of 10
      with a 128x128 matrix. We concluded that, in this phantom study,
      tomoscintimammography with IR provides a significant improvement in the detection
      of small-sized breast tumours compared with planar images. In addition, for
      tomoscintigraphic images, a 128x128 matrix is preferable to a 64x64 matrix. Those
      results have, of course, to be confirmed in vivo in a large population of
      patients with small-sized breast lesions.

PMID- 11505216
TI  - Haemodynamic characterization of young normotensive men carrying the 825T-allele
      of the G-protein beta3 subunit.
AB  - A C825T polymorphism was recently identified in the gene for the G-protein beta3
      subunit, the T-allele being associated with hypertension. To better understand
      the underlying pathophysiological mechanisms, we compared the haemodynamics of
      young healthy males with and without the T-allele. In three studies, subjects
      were investigated with regard to cardiac and vascular function at rest and
      following intravenous administration of the beta-adrenoceptor antagonist,
      propranolol, and the alpha2-adrenoceptor agonist, alpha-methylnoradrenaline, and
      with regard to local venous vasoconstriction in the dorsal hand vein in situ
      following infusion of the alpha2-adrenoceptor agonist, azepexol. alpha2
      Adrenoceptor agonists were chosen as vasoconstrictor drugs since alpha2
      adrenoceptors couple to pertussis toxin (PTX)-sensitive G-proteins and since in
      vitro studies have demonstrated enhanced signal transduction of PTX-dependent
      pathways in the presence of the T-allele. Total peripheral resistance was
      determined as a parameter of vasoconstrictor tone and heart rate, stroke volume
      and systolic time intervals for cardiac function. T-allele carriers had a
      significantly elevated stroke volume and lower total peripheral resistance at
      baseline. After propranolol, their fall in stroke volume was significantly
      greater. During alpha-methylnoradrenaline infusion, elevation of total peripheral
      resistance was not increased relative to controls. Similarly, the constriction
      response of the dorsal hand vein to azepexol was not different. Our study does
      not support the idea of increased vasoconstrictor tone in T-allele carriers
      either at rest or during stimulation of alpha2-adrenoceptors. However, this
      allele may be associated with elevated cardiac stroke volume.

PMID- 11505217
TI  - Association between the 5' UTR variant C178T of the serotonin receptor gene HTR3A
      and bipolar affective disorder.
AB  - Serotonin receptor type 3 is a ligand-gated ion channel implicated in behavioural
      disorders. Our objective was to identify nucleotide variants in a specific
      portion of the 5' region of the serotonin receptor gene (HTR3A) containing
      upstream open reading frames (uORFs) and to investigate their effect on bipolar
      disease. Mutations in uORFs have been recently shown to cause disease by changing
      expression on the translational level. We identified one polymorphism, C195T, and
      one missense mutation, C178T (Pro16Ser) within an upstream open reading frame. No
      significant association was found between the C195T polymorphism and bipolar
      affective disorder. A significant association was, however, found between the
      variant C178T in 156 patients with bipolar disorder compared to 156 healthy
      controls (P = 0.00016). To investigate the relevance of this variant on gene
      expression, luciferase reporter constructs containing the C178T (Pro16Ser) allele
      were established and compared to the C178T plus C195T and wild-type alleles.
      Reporter constructs containing the C178T (Pro16Ser) allele drove 245% and 138%
      expression compared to the wild-type allele. These findings show that the
      C178T(Pro16Ser) variant in HTR3A may represent a functional variant and affect
      the susceptibility to bipolar disorder.

PMID- 11505218
TI  - Cytochrome P450 2D6.1 and cytochrome P450 2D6.10 differ in catalytic activity for
      multiple substrates.
AB  - CYP2D6 is involved in the metabolism of several classes of drugs, including
      tricyclic antidepressants, selective serotonin reuptake inhibitors and various
      amphetamines. CYP2D6*10 is an allelic variant, producing an enzyme with Pro34Ser
      and Ser486Thr amino acid substitutions. Approximately 75% of Asians possess the
      *10 allele. We sought to further characterize CYP2D6.10 catalytically in vitro in
      a baculovirus expression system using various substrates and inhibitors, in
      comparison to CYP2D6.1 (wild-type). Using dextromethorphan (DEX), P
      methoxyamphetamine, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and (+/-)3,4
      methylenedioxymethamphetamine (MDMA), the ratios of intrinsic clearance (Vmax/Km)
      of *1 to *10 were 50, 34, 22 and 123, respectively. The CYP2D6 substrates
      amitriptyline, and (+) and (-) methamphetamine (MAMP) are both p-hydroxylated and
      N-demethylated (NDM). The intrinsic clearance *1/*10 ratios were 42, 30 and 67
      for the p-hydroxylation; and 60, 120 and 157 for the NDM, respectively,
      illustrating chemical pathway and enantiomeric selectivity for MAMP. It was
      apparent that (+) and (-) MAMP NDM and MDMA demethylenation were most
      significantly different in CYP2D6.10. Using DEX as the substrate, the ratios of
      Ki(*10)/Ki(*1) for inhibitors were: budipine (1.3), sparteine (1.6), debrisoquine
      (8.1), fluoxetine (16), norfluoxetine (30), paroxetine (14), MDMA (21) and MMDA-2
      (7.1), indicating that CYP2D6.10 shows drug-specific altered susceptibility to
      inhibition. Taken together, these data suggest that CYP2D6*10/*10 individuals may
      be expected to require different drug doses; and show altered susceptibility to
      toxicity, interaction risk and, in the case of the amphetamines, drug dependence
      and toxicity compared to CYP2D6*1/*1 individuals.

PMID- 11505220
TI  - CYP1A1 levels in lung tissue of tobacco smokers and polymorphisms of CYP1A1 and
      aromatic hydrocarbon receptor.
AB  - Induction of a polycyclic aromatic hydrocarbon-metabolizing cytochrome P450
      isoform CYP1A1 is regulated by aromatic hydrocarbon receptor (AHR). High
      inducibility of CYP1A1, possibly due to genetic polymorphisms, has been
      considered to be a risk factor for lung cancer in tobacco smokers. The
      relationship between low or high pulmonary expression of CYP1A1 and polymorphic
      genotypes of CYP1A1 and AHR was investigated in 73 active smokers. CYP1A1
      expression was determined in surgical lung samples by measuring ethoxyresorufin O
      deethylase (EROD) activity and by immunostaining for CYP1A1 protein. The most
      common allelic variants of CYP1A1 and AHR in Finns, i.e. the MspI variant
      (CYP1A1*2A), I462V variant (CYP1A1*2B), and -459C to T variant of CYP1A1 and the
      R554K variant (AHR*2) of AHR were studied using polymerase chain reaction based
      methods. EROD activity correlated positively with the daily cigarette consumption
      (r = 0.45). There was additional variation in EROD activity independent of the
      amount of smoking e.g. among those who smoked one pack per day until the day of
      operation, EROD activity ranged from 4-142 (median 48) pmol/min/mg. The
      frequencies of the MspI, 462V, and -459T variant alleles of CYP1A1 and 554K
      variant allele of AHR were 0.158, 0.055, 0.055 and 0.075, respectively. No
      differences were observed in the frequencies of polymorphic genotypes between the
      smokers with low and those with high expression, when the relationship was
      studied using a regression analysis adjusted for cigarette consumption. Our
      results thus indicate that the interindividual variation of CYP1A1 levels in
      smokers' lung tissue is not attributable to genetic polymorphisms of CYP1A1 or
      AHR tested in this study.

PMID- 11505219
TI  - Analysis of the CYP2D6 gene polymorphism and enzyme activity in African-Americans
      in southern California.
AB  - Despite its importance in drug metabolism and disease susceptibility, CYP2D6
      activity and genetic polymorphism have rarely been investigated in African
      American populations. In order to bridge this gap, we examined the genotype and
      phenotype of the enzyme in 154 African-American (AA) and 143 Caucasian (C) normal
      volunteers. AAs are significantly more likely to possess *17 and *5, but less
      likely to have *4. Overall, the two groups were similar in their CYP2D6 activity
      as measured with dextromethorphan as the probe (metabolic ratio 2.21 +/- 0.78 for
      AAs; 2.11 +/- 0.86 for Cs; t = 1.02, NS). Two of four AAs and six of seven Cs
      were classified as poor metabolizers and have two nonfunctioning alleles. CYP2D6
      activity is determined by *17, *4, *5 and age in AAs (r2 = 0.33, f = 18.8, P <
      0.001) and by *4 and *XN in Cs (r2 = 0.14, f = 10.8, P < 0.001). These results
      support previous findings demonstrating the importance of *17 in determining
      CYP2D6 activity in AAs.

PMID- 11505221
TI  - Functional characterization of nucleotide polymorphisms in the coding region of N
      acetyltransferase 1.
AB  - N-acetyltransferase 1 (NAT1) catalyses the activation and/or deactivation of
      aromatic and heterocyclic amine carcinogens. A genetic polymorphism in NAT1 is
      associated with an increased risk of various cancers and drug toxicities, but
      epidemiological investigations are severely compromised by a poor understanding
      of the relationship between NAT1 genotype and phenotype. Human reference NAT1*4
      and 12 known human NAT1 allelic variants possessing nucleotide polymorphisms in
      the NAT1 coding region were cloned and expressed in yeast (Schizosaccharomyces
      pombe). Large reductions in N- and O-acetyltransferase catalytic activities were
      observed for recombinant NAT1 allozymes encoded by NAT1*14B, NAT1*15, NAT1*17,
      NAT1*19 and NAT1*22. Each of these alleles exhibited NAT1 protein expression
      levels below the limit of detection as measured by Western blot. No differences
      between high and low activity NAT1 alleles were observed in relative mRNA
      expression or relative transformation efficiency. The recombinant NAT1 17 and
      NAT1 22 allozymes showed reduced intrinsic stability when compared with NAT1 4. 2
      Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) N-acetylation was not
      catalysed by any of the NAT1 allozymes. Large differences in the metabolic
      activation via O-acetylation of 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5
      b]pyridine (N-hydroxy-PhIP) were noted for NAT1 allelic variants. The results of
      these studies suggest an important role for the NAT1 genetic polymorphism in
      metabolism of aromatic and heterocyclic amine carcinogens. Furthermore, these
      results suggest that low NAT1 phenotype results from NAT1 allelic variants that
      encode reduced expression of NAT1 and/or less-stable NAT1 protein.

PMID- 11505222
TI  - Association of GSTT1 non-null and NAT1 slow/rapid genotypes with von Hippel
      Lindau tumour suppressor gene transversions in sporadic renal cell carcinoma.
AB  - The von Hippel-Lindau (VHL) tumour suppressor gene is commonly mutated in renal
      cell carcinoma of clear cell type (CCRCC). We investigated the possible
      relationship between VHL mutations in sporadic CCRCC and polymorphism of genes
      encoding enzymes involved in carcinogen metabolism: two cytochrome P450
      monooxygenases (CYP1A1 and CYP2D6), one NAD[P]H:quinone oxidoreductase (NQO1),
      three glutathione S-transferases (GSTM1, GSTT1 and GSTP1) and two arylamine N
      acetyltransferases (NAT1 and NAT2). We analysed DNA from tumour and nontumoural
      kidney tissue from 195 CCRCC patients. Single VHL mutations were identified in 88
      patients and double mutations were present in two patients. Nine of 18
      transversions were GC to TA, four were AT to TA, four were GC to CG and one was
      AT to CG. Ten of 19 transitions were GC to AT and nine were AT to GC. We also
      identified 53 frameshifts and two GC to AT at CpG. An excess of transversions was
      observed in a subset of patients with active GSTT1 [GSTT1 (+) genotype] and
      probably defective NAT1 (NAT1 S/R variant genotype). All 18 transversions were in
      GSTT1 (+) patients, whereas only 76% of transitions (P = 0.05) and 81% of the
      other mutations (P = 0.06) occurred in this genotype. We found that 28% of the
      transversions were in the NAT1 S/R genotype versus 12% of the transitions (P =
      0.40) and 4% of the other mutations (P = 0.01). This suggests that
      pharmacogenetic polymorphisms may be associated with the type of acquired VHL
      mutation, which may modulate CCRCC development.

PMID- 11505223
TI  - Impact of GSTM1 on aromatic-DNA adducts and p53 accumulation in human skin and
      lymphocytes.
AB  - The cellular response to DNA damage is often a p53-mediated cell cycle arrest to
      provide time for DNA repair or to direct damaged cells into apoptosis. In this
      study, the impact of glutathione-S-transferase M1 (GSTM1) on DNA damage and
      subsequent p53-protein accumulation was examined in lymphocytes of healthy
      volunteers in vitro exposed to benzo[a]pyrene-diol-epoxide (BPDE) and in skin of
      atopic eczema patients topically treated with coal tar. DNA adducts were
      determined by immunocytochemical staining (ICC) and 32P-postlabelling, p53
      accumulation was studied by ICC and the GSTM1 genotype was assessed by polymerase
      chain reaction. In cultured lymphocytes treated with 2.5 microM BPDE for 18 h,
      increased levels of p53 were found, which were positively related to BPDE-DNA
      adduct levels assessed by ICC (rs = 0.66, P < 0.001) and 32P-postlabelling (rs =
      0.56, P < 0.001) and appeared to be higher in GSTM1(-/-) than in GSTM1(+)
      subjects (P = 0.003). In skin biopsies of coal tar treated eczema patients, p53
      levels were elevated in 7/10 patients and a correlation was observed between p53
      and DNA adduct levels (rs = 0.50, P = 0.029). GSTM1(-/-) subjects contained
      higher levels of p53 in the stratum basale than GSTM1(+) individuals (P = 0.026),
      but no influence of GSTM1 on DNA adduct levels was observed. Thus, p53
      accumulates in human skin and lymphocytes as a protective mechanism against
      polycyclic aromatic hydrocarbon induced DNA damage, and this is more pronounced
      in GSTM1(-/-) compared to GSTM1(+) individuals.

PMID- 11505224
TI  - The -141C Ins/Del polymorphism in the dopamine D2 receptor gene promoter region
      is associated with anxiolytic and antidepressive effects during treatment with
      dopamine antagonists in schizophrenic patients.
AB  - Previous studies have demonstrated a lower density of dopamine D2 receptor (DRD2)
      in subjects without Del alleles of the -141C Ins/Del polymorphism in DRD2 gene
      promoter region than in those with one or two Del alleles. The present study
      aimed to examine whether the -141C Ins/Del DRD2 promoter polymorphism is related
      to therapeutic response to selective DRD2 antagonists in the treatment of
      schizophrenia. Subjects consisted of 49 acutely exacerbated schizophrenic
      inpatients treated with bromperidol (30 cases, mean dose +/- SD: 11.4 +/- 4.8
      mg/day) or nemonapride (19 cases, 18 mg/day). Clinical symptoms were evaluated by
      the Brief Psychiatric Rating Scale (BPRS) before and 3 weeks after the treatment.
      The -141C Ins/Del DRD2 genotypes, the Ins and Del alleles, were determined by a
      polymerase chain reaction method. Thirty-five patients were homozygous for the
      Ins allele and 14 were heterozygous for the Del and Ins alleles. The patients
      without Del allele showed a higher percentage of improvement in anxiety
      depression symptoms than those with Del allele (58.5 +/- 44.5% versus 24.1 +/-
      48.2%) after 3 weeks of treatment while percentage improvement in total BPRS or
      other subgrouped symptoms (positive, negative, excitement and cognitive symptoms)
      was similar between the two genotype groups. The present results suggest that the
      -141C Ins/Del DRD2 polymorphism is associated with anxiolytic and antidepressive
      effects of neuroleptic treatment in schizophrenic patients.

PMID- 11505225
TI  - Prevalence and distribution of oral candidosis in patients with AIDS. 

PMID- 11505226
TI  - Minor recurrent aphthous stomatitis: Clinic characteristics hematologic
      deficiencies in 60 patients. 

PMID- 11505228
TI  - Vesiculo-Bullous Diseases diagnosis in the oral mucosa: Intraepithelial-cohesion
      and epithelio-conective-adherence disorders. 

PMID- 11505227
TI  - Pharmacological bases of the antibiotic therapy in odontogenic infections. 

PMID- 11505229
TI  - Melkersson-Rosenthal syndrome. A case report. 

PMID- 11505230
TI  - Oral paramandibular fibromatosis. Report of two cases. 

PMID- 11505232
TI  - Mandibular Pasmocytoma. First manifestation of a multiple mieloma. 

PMID- 11505231
TI  - Systemic Lupus Erythematosus: Presentation of a clinical case in whitch the oral
      lesions were the first manifestation and the indicator of the patient's rapid
      unfavourable ending. 

PMID- 11505233
TI  - Oral leucoplakia: histopathologic study or 55 cases. 

PMID- 11505234
TI  - Presence of HPV 16 sequences in oral squamous cell carcinomas. 

PMID- 11505235
TI  - Oral candidiasis:etiology. pathogenesis and laboratory diagnosis. 

PMID- 11505236
TI  - Disorders of secretion: hiposecretion and sialorrhea. 

PMID- 11505237
TI  - Congenital Dyskeratosis: report of a case with oral lesions. 

PMID- 11505238
TI  - Primary angiosarcoma of the gingiva. 

PMID- 11505239
TI  - Leishmaniasis: report of a case with oral lesions. 

PMID- 11505240
TI  - Mind over matter: does it matter?

PMID- 11505242
TI  - Falls prevention in older adults.

PMID- 11505243
TI  - Outcomes of comfort touch in institutionalized elderly female residents.
AB  - Comfort touch as a holistic nursing intervention has gained considerable
      attention in the past decade. The purpose of this experimental study was to
      examine whether comfort touch improved the perceptions of self-esteem, well-being
      and social processes, health status, life satisfaction and self-actualization,
      and faith or belief and self-responsibility in 45 institutionalized elderly
      female residents. Results revealed that comfort touch significantly improved the
      perceptions of all elements. This article offers recommendations for practice,
      research, and education.

PMID- 11505244
TI  - Memory improvement program for elderly cancer survivors.
AB  - Elderly cancer survivors report difficulty with attention, concentration, and
      memory. This study tested the effectiveness of the Cognitive Behavioral Model of
      Everyday Memory, an efficacy-based intervention designed to improve memory
      performance, memory self-efficacy, and metamemory in older adult cancer survivors
      and those with other chronic conditions. The study provides interesting new
      evidence that the responses of a group of elders to training varies depending on
      their health status.

PMID- 11505245
TI  - A trio to treasure: the elderly, the nurse, and music.
AB  - Music is a powerful tool for maintaining and restoring health and is particularly
      suited to elder care. Music can be used to induce relaxation, alter moods, and
      create distraction. Music's effect is attributed to its vibrational properties,
      which are processed through the senses and integrated within the central nervous
      system. Nurses have a major responsibility to understand, appreciate, and use
      music in their practice.

PMID- 11505246
TI  - Clinical use of tai chi in elderly populations.
AB  - Tai chi, a type of low-intensity exercise, has received growing attention in both
      eastern and western cultures, especially its use with the most rapidly increasing
      segment of the population-elders. Previous research findings further supported
      the idea that tai chi is appropriate for elderly populations and helps promote
      their well-being. In this article, the beneficial effects of tai chi for elders
      are summarized, resources to increase awareness about the exercise are provided,
      and ways to promote tai chi in elderly populations are suggested.

PMID- 11505247
TI  - A program on complementary therapies for long-term care nursing assistants.
AB  - Nursing assistants (NAs) receive insufficient support in the face of heavy
      workloads and challenging job demands. This article describes a course on
      complementary therapies (CTs) intended to improve NAs' quality of life by helping
      them plan, develop, implement, and evaluate CTs. Future studies may examine the
      impact, if any, such courses have on recruitment and retention.

PMID- 11505248
TI  - Management update: how will we have enough nurses?

PMID- 11505249
TI  - Behind the scenes: visionary foundations.

PMID- 11505250
TI  - Motorized cart driver safety in assisted living.
AB  - When a group of residents at a life care facility purchased motorized carts to
      move around the 350,000-square-foot facility, staff members were faced with the
      need to ensure the safety of both drivers and pedestrians. This article describes
      a safety assessment procedure developed for cart drivers who lived in the
      assisted living area of the community. Five performance criteria were selected
      for the safety assessment: the ability to safely moving into and out of the
      vehicle, demonstrate safe reaction times, take appropriate evasive action to
      sudden obstructions in the driver's path, turn the vehicle around safely, and
      park the vehicle without hitting walls or other objects.

PMID- 11505251
TI  - Newest developments in dementia treatment and prevention.

PMID- 11505252
TI  - Prospective payment in home care: an overview.

PMID- 11505253
TI  - Nutrition, supplements, and aging.

PMID- 11505254
TI  - Organize for multicentered clinical trials.

PMID- 11505255
TI  - Anesthesia and OMFS.

PMID- 11505256
TI  - Alcoholism.

PMID- 11505257
TI  - Anesthetic efficacy of unilateral and bilateral inferior alveolar nerve blocks to
      determine cross innervation in anterior teeth.
AB  - OBJECTIVE: The purpose of this prospective randomized study was to measure the
      degree of anesthesia obtained with unilateral and bilateral inferior alveolar
      nerve blocks to determine whether cross innervation occurs in anterior teeth.
      STUDY DESIGN: Through use of a repeated-measures design, 38 subjects randomly
      received unilateral or bilateral inferior alveolar nerve blocks at two separate
      appointments. Each inferior alveolar nerve block used 3.6 mL of 2% lidocaine with
      1:100,000 epinephrine. Mandibular anterior teeth were blindly pulp-tested at 4
      minute cycles for 60 minutes' postinjection. No response from the subject to the
      maximum output (80 reading) of the pulp tester was used as the criterion for
      pulpal anesthesia. Anesthesia was considered successful when 2 consecutive 80
      readings were obtained. RESULTS: One hundred percent of the subjects had lip
      numbness with each of the inferior alveolar nerve block techniques. Anesthetic
      success rates of the unilateral inferior alveolar nerve block were 39% for the
      central incisor, 50% for the lateral incisor, and 68% for the canine. For the
      bilateral inferior alveolar nerve blocks, success rates were 66% for the central
      incisor, 74% for the lateral incisor, and 76% for the canine. The bilateral
      inferior alveolar nerve block success rates were significantly (P <.05) higher
      for the central and lateral incisors when compared with the success rates of the
      unilateral inferior alveolar nerve block. CONCLUSIONS: Cross innervation does
      seem to occur in mandibular central and lateral incisors. However, the success
      rates in these teeth with bilateral inferior alveolar nerve blocks were below
      75%. The failure of the inferior alveolar nerve blocks to anesthetize the
      anterior teeth was the overriding reason for failure. Clinically, bilateral
      inferior alveolar nerve blocks to provide profound pulpal anesthesia in
      mandibular anterior teeth are not recommended on the basis of the results of this
      study.

PMID- 11505258
TI  - Bone volume after secondary bone grafting in unilateral and bilateral clefts
      determined by computed tomography scans.
AB  - OBJECTIVE: The purpose of this study was to evaluate the outcome of bone grafts
      in cleft palate patients, thus assessing the amount of bone necessary to
      facilitate eruption-especially in the buccopalatal direction-of the permanent
      canine into the bone graft. STUDY DESIGN: Computed tomography scans taken
      immediately postoperatively and 1 year postoperatively of 42 unilateral and of 8
      bilateral cleft lip and palate patients who underwent surgery at the age of 9
      years (early secondary bone graft) or 12 years (late secondary bone graft) were
      compared. Three slices from the computed tomography scans taken immediately after
      the surgery were selected from the center of the bone graft and were then
      compared with corresponding slices from the 1-year postoperative computed
      tomography scans. Statistical analysis was performed by using the Wilcoxon 2
      sample rank sum test. RESULTS: In the unilateral cleft group, 70% of the
      transplanted bone remained in the cleft area after 1 year, whereas in the
      bilateral cleft group, only 45% of the initial bone graft remained after 1 year.
      CONCLUSION: No statistically significant difference was found between early
      secondary bone grafting and late secondary bone grafting. In most cases, a
      sufficient amount of bone was present in the target area to facilitate eruption
      of the permanent canine.

PMID- 11505260
TI  - Third molar outcomes from age 18 to 26: findings from a population-based New
      Zealand longitudinal study.
AB  - OBJECTIVE: The purpose of this study was to describe the presence and impaction
      status of people's third molars at age 18 years, as well as the observed changes
      in their clinical status between ages 18 and 26 years. STUDY DESIGN: Eight
      hundred twenty-one participants in a prospective cohort study were dentally
      examined at ages 18 and 26 years, and panoramic radiographs were taken at age 18
      years but not at 26 years. For each tooth, its radiographic impaction status at
      age 18 years was compared with the clinical status by age 26 years. RESULTS: Of
      the 2857 third molars assessed at age 18 years, 92.8% were able to be followed up
      clinically at age 26 years. Approximately 54.9% of the teeth that were not
      impacted by age 18 had erupted by 26 years. Of the teeth that were impacted by
      age 18, 33.7% had fully erupted by age 26, 31.4% had been extracted, and 13.1%
      remained unerupted. Of the maxillary teeth that were categorized as "impacted" at
      age 18 years, 36.2% had fully erupted by age 26, whereas only 25.6% of the
      mandibular teeth had done so (P <.01). Fewer mandibular teeth than maxillary
      teeth remained unerupted by the time the patient was 26 years old (27.4% and
      41.4%, respectively; P <.01), but there was no significant difference between the
      jaws in the proportion of impacted teeth at age 18 years that had been extracted
      by age 26 years (29.6% and 30.3%, respectively). For mesioangularly impacted
      third molars, 39.3% of maxillary teeth and 20.4% of mandibular teeth had fully
      erupted by age 26. Of the third molars that were mesioangularly impacted at age
      18 years, 39.3% of maxillary teeth and 20.4% of mandibular teeth had fully
      erupted by age 26 years, whereas almost one-third of each had been extracted. Of
      the distoangularly impacted third molars, 20.4% of the maxillary teeth and one
      third of the mandibular teeth had erupted by age 26, with 21.6% of the maxillary
      teeth and 31.6% of the mandibular teeth having been extracted. CONCLUSION: Other
      than horizontally impacted third molars, a substantial proportion of other
      impaction types do erupt fully, and radiographically apparent impaction in late
      adolescence should not be sufficient grounds for their prophylactic removal in
      the absence of other clinical indications.

PMID- 11505259
TI  - Maintenance of soft tissue changes after rigid versus wire fixation for
      mandibular advancement, with and without genioplasty.
AB  - OBJECTIVE: This multisite prospective randomized clinical trial examined 2-year
      longitudinal soft tissue profile changes after bilateral sagittal split osteotomy
      for mandibular advancement by using rigid or wire fixation, with and without
      genioplasty. STUDY DESIGN: The study sample consisted of 127 subjects. The rigid
      fixation group (n = 78) received 2-mm bicortical position screws, whereas the
      wire-fixation group (n = 49) received inferior border wires. In the rigid
      fixation group, 35 subjects underwent genioplasty, whereas 24 subjects underwent
      genioplasty in the wire-fixation group. Soft tissue profile changes of labrale
      inferius, B-point, and pogonion were obtained from digitized cephalometric films
      taken immediately before surgery and up to 2 years after surgery. RESULTS:
      Regardless of fixation technique, subjects who had genioplasty in conjunction
      with the mandibular advancement had the largest surgical movement and the largest
      postsurgical change (P <.05). When all variables were constant, fixation
      technique was associated with maintenance of soft tissue change. Subjects who
      underwent rigid fixation maintained more soft tissue change than patients who
      underwent wire fixation. CONCLUSIONS: These findings suggest that subjects
      undergoing rigid fixation and genioplasty maintained the most soft tissue
      advancement.

PMID- 11505261
TI  - Salivary gland dysfunction: a review of systemic therapies.
AB  - Xerostomia may result from salivary dysfunction secondary to a variety of
      conditions, including medications, autoimmune disease, and tumoricidal therapy.
      As the geriatric population increases, the incidence of xerostomia will increase
      and the oral manifestations will continue to be a challenge to the clinician.
      Common oral manifestations resulting from decreased salivary flow include
      increased dental caries, fungal infections, and dysphagia. Treatment for salivary
      gland dysfunction is currently limited because of a lack of controlled clinical
      trials. Medications that have been studied in clinical trials are emphasized in
      this article. The aim of this article is to briefly review salivary gland
      physiology and to summarize the suggested systemic treatment modalities for
      xerostomia that emphasize controlled clinical trials.

PMID- 11505262
TI  - Mefloquine-induced trigeminal sensory neuropathy.
AB  - Trigeminal sensory neuropathy is an important finding, often indicative of trauma
      but sometimes related to neoplasia, infections, demyelinating conditions,
      connective tissue disorders, other disorders, or, occasionally, drugs. This paper
      reports on a patient with sudden-onset trigeminal sensory neuropathy of the lip
      that proved to be drug-induced, secondary to the antimalarial drug mefloquine.
      This appears to be the first report of sensory impairment in the orofacial region
      from exposure to mefloquine.

PMID- 11505263
TI  - The relationship between gastric-oral Helicobacter pylori and oral hygiene in
      patients with vitamin B12-deficiency anemia.
AB  - OBJECTIVE: The aim of this study was to determine whether a relationship exists
      between gastric and oral Helicobacter pylori and oral hygiene in patients with
      vitamin B12 deficiency. STUDY DESIGN: One hundred eight patients with vitamin B12
      deficiency who were H pylori -positive in their gastric mucosa were enrolled in
      the study. These patients were divided into 3 groups determined by Oral Hygiene
      Index (OHI) scores of good, fair, or poor. H pylori was detected in the dental
      plaque with camphylobacter-like organism test gels. All patients were treated
      with a combination regimen to eradicate H pylori. RESULTS: H pylori positivity in
      dental plaque was correlated with OHI scores; the positivity was 28.5%, 90.2%, or
      100% in patients with good, fair, or poor OHI scores, respectively. The
      eradication of H pylori was associated with recovery from anemia and increased
      serum vitamin B12 level (P <.0001 and P <.0001). The patients with poor OHI
      scores had the most frequent gastric recurrence of H pylori (58.3%) compared with
      those with fair OHI scores (41.2%) and good OHI scores (4.8%). CONCLUSIONS: H
      pylori seems to be an etiologic factor in vitamin B12 deficiency, since anemia
      was cured and the level of vitamin B12 in the serum increased as a result of its
      eradication. However, eradication of H pylori from gastric mucosa alone is not
      enough to prevent gastric recurrence of the bacteria. Proper oral hygiene must be
      established to eliminate H pylori in dental plaque. Therefore, we suggest that
      control of H pylori in dental plaque is necessary to control recurrence of H
      pylori.

PMID- 11505264
TI  - A systematic review of the effectiveness of antifungal drugs for the prevention
      and treatment of oropharyngeal candidiasis in HIV-positive patients.
AB  - OBJECTIVE: A systematic review of randomized clinical trials published between
      1966 and April 2000 was undertaken to determine the strength of evidence for the
      effectiveness of antifungal drugs (nystatin, clotrimazole, amphotericin B,
      fluconazole, ketoconazole, and itraconazole) to prevent and treat oral
      candidiasis in human immunodeficiency virus-positive patients. STUDY DESIGN: An
      automated database search identified 366 articles. Six met inclusion and
      exclusion criteria with respect to prophylaxis; 12 met criteria for treatment of
      oral candidiasis. RESULTS: The evidence for the prophylactic efficacy of
      fluconazole is good, although insufficient to draw conclusions about the other
      antifungals. Evidence for treatment effectiveness is insufficient for
      amphotericin B but good for nystatin, clotrimazole, fluconazole, ketoconazole,
      and itraconazole. CONCLUSION: Suggestions for strengthening the evidence base
      include the following: use of larger, more well-defined groups; control for
      immunologic status, viral load, history of oral candidiasis, past exposure to
      antifungals, baseline oral Candida carriage, drug interactions, and
      antiretroviral therapy; and consistent use of compliance monitors, fungal
      speciation, and susceptibility testing.

PMID- 11505265
TI  - Nasal mucosal headache presenting as orofacial pain: a review of the literature
      and a case report.
AB  - Headaches are a significant component of many facial pain syndromes. These facial
      pain/headache syndromes often have various etiologies, including neurologic,
      vascular, musculoskeletal, or combinations of vascular/musculoskeletal origins.
      Referred rhinologic headache, however, can be overlooked as a cause of facial
      pain in the dental literature. We report a case of nasal mucosal headache that
      presented as facial pain and include a review of the literature.

PMID- 11505266
TI  - Epstein-Barr virus detection in non-Hodgkin's lymphoma of the oral cavity: an
      immunocytochemical and in situ hybridization study.
AB  - OBJECTIVE: The purpose of this study was to histologically characterize a series
      of oral non-Hodgkin's lymphomas (NHLs) and to investigate latent and lytic
      Epstein-Barr virus (EBV) infection in these. STUDY DESIGN: The revised European
      American Lymphoma classification system (41) was used to categorize 58 cases of
      oral NHL, which included 9 immunosuppression-related NHLs. EBV infection was
      determined by in situ hybridization for Epstein-Barr virus-encoded RNA and by
      immunohistochemistry for the EBV antigens latency membrane protein, Epstein-Barr
      nuclear antigen-2 (EBNA2) and Z EBV replication activator protein. RESULTS: Most
      tumors were B-cell lymphomas (78%), but the proportion of T-cell lymphomas was
      surprisingly high (22%). The most common histologic subtypes were diffuse large B
      cell lymphomas (45%), peripheral T-cell lymphomas (19%), and follicle center
      lymphomas (14%). Two thirds of the known immunosuppression-related NHLs were T
      cell lymphomas. All of the immunosuppression-related tumors were EBV-infected,
      whereas the EBV infection rate in the NHLs of the remaining patients presumed to
      be immunocompetent was only 9%. Most EBV-positive tumors expressed neither of the
      latent antigens (ie, latency membrane protein and Epstein-Barr nuclear antigen
      2), and coexpression of the 2 was observed only in immunosuppressed patients. Z
      EBV replication activator protein expression, which is indicative of replicative
      infection, occurred only in immunosuppressed individuals. CONCLUSIONS: Diffuse
      large B-cell lymphomas were the most common histologic subtype of oral NHLs, but
      T-cell lymphomas were relatively common and frequently occurred in states of
      immunosuppression. EBV may play a limited role in the initiation of lymphoma in
      the immunocompetent patient, but the virus may be of importance in progression of
      the disease in those patients with more aggressive tumors, as immunosuppression
      occurs.

PMID- 11505267
TI  - MDM2+/CDK4+/p53+ oral liposarcoma: case report and review of the literature.
AB  - Although liposarcoma is one of the most common soft tissue sarcomas, its location
      in the oral cavity is very rare. To our knowledge, only 43 cases of liposarcoma
      originating in the oral tissues have been reported in the English-language
      literature. In this article, we report a case of well-differentiated liposarcoma
      affecting the cheek of a 28-year-old man and review the oral liposarcoma
      literature. Immunohistochemical analysis of the tumor revealed an
      MDM2+/CDK4+/p53+ immunophenotype that is consistent with the immunohistochemical
      profile of well-differentiated liposarcoma originating in other areas of the
      body. Quantitative polymerase chain reaction analysis of the DNA levels of the
      MDM2 (human homologue of the murine double-minute type 2), CDK4 (cyclin-dependent
      kinase 4), and SAS (sarcoma amplified sequence), genes was performed, revealing
      only SAS gene amplification. The possibility of misdiagnosis of oral liposarcoma
      because of its sometimes inconspicuous clinical and microscopic features is
      emphasized. Careful pathologic examination of liposarcoma is essential for
      discrimination from benign adipose tissue neoplasms and for precise histologic
      classification, both of major prognostic significance. Possible implications of
      molecular and cytogenetic analysis for unraveling the pathogenesis and
      determining the prognosis of liposarcoma are discussed.

PMID- 11505268
TI  - Adenomatous polyposis coli gene mutation and decreased wild-type p53 protein
      expression in oral submucous fibrosis: a preliminary investigation.
AB  - OBJECTIVE: The purpose of this study was to identify the adenomatous polyposis
      coli (APC) tumor suppressor gene mutation and level of wild-type p53 protein
      expression in patients with oral submucous fibrosis (OSF). STUDY DESIGN: Cells
      from OSF and control subjects were cultured in Dulbecco modified Eagle medium
      with 10% fetal bovine serum at 37 degrees C. Genomic DNA was extracted from
      cultured cells and used as a template for polymerase chain reaction amplification
      of the APC tumor suppressor gene. The presence of wild-type p53 protein in cell
      lysates of cultured cells was analyzed by Western blot. Data were analyzed by the
      sign test for nonparametric samples and by analysis of variance. RESULTS: The
      results showed that the APC gene of explant cultured cells from OSF patients
      (8/8) had a CGA-to-GGA transition mutation at codon 498 that resulted in an Arg
      to-Gly missense mutation (P <.01). All (8/8) normal HGF cultures revealed
      expression of the wild-type APC protein. Cells cultured from 7 of 8 OSF patients
      were also found to have a single nucleotide deletion at nucleotide 1494 that
      resulted in creating a stop codon (TGA) at codon 504 (P <.01). This created a
      premature signal for the endpoint of translation and thus resulted in the
      generation of a truncated protein product that encodes a polypeptide of 503 amino
      acid residue. It was found that wild- type p53 protein in human gingival
      fibroblast cell cultures was significantly higher than in OSF cells (P <.01).
      CONCLUSION: Alterations of the APC and wild-type p53 tumor suppressor genes in
      OSF may imply a risk for progression to oral cancer.

PMID- 11505269
TI  - A new bacterial species associated with failed endodontic treatment:
      identification and description of Actinomyces radicidentis.
AB  - OBJECTIVE: This report describes 2 endodontic patients who had persistent signs
      and symptoms after conventional root canal treatment. The aim of this study was
      to determine what microorganisms were present in the root canals of the teeth
      with failed endodontic therapy. STUDY DESIGN: After removal of the root fillings,
      the canals were sampled by advanced microbiological techniques and the isolates
      were characterized by various tests. RESULTS: Bacteria, which grew in pure
      cultures, were isolated in each case. The bacteria were similar to each other and
      were classified as Actinomyces on the basis of phylogenic and phenotypic
      evidence. The bacteria were different from others within the genus, thus
      warranting designation as a new species, Actinomyces radicidentis. CONCLUSIONS:
      The 2 cases of endodontic failure were infected with A radicidentis, a new
      Actinomyces species. This bacterium joins a restricted group of other
      microorganisms that have been associated with failure of root canal treatment.

PMID- 11505270
TI  - Shaping ability of Hero 642 rotary nickel-titanium instruments and stainless
      steel hand K-Flexofiles in simulated curved root canals.
AB  - OBJECTIVE: The purpose of this study was to compare the shaping ability of Hero
      642 rotary nickel-titanium instruments with that of stainless steel hand K
      Flexofiles. STUDY DESIGN: Simulated 28 degrees and 35 degrees curved canals were
      prepared with Hero 642 instruments by using a crown-down preparation and with K
      Flexofiles by using a reaming working motion (n = 24 canals in each case). All
      canals were sequentially prepared up to size 35. Preinstrumental and
      postinstrumental images were taken, and assessment of the canal shapes was
      completed with a computer image analysis program. Material removal was measured
      at 20 measuring points, beginning 1 mm away from the apex. In addition,
      preparation time, changes of working length, and instrument failures were
      recorded. RESULTS: In comparison with stainless steel K-Flexofiles, rotary Hero
      642 instruments achieved better canal geometry and showed less canal
      transportation, both in canals with 28 degrees curves and in canals with 35
      degrees curves. Three Hero instruments separated, whereas none of the K
      Flexofiles separated. In 28 degrees curved canals, Hero instruments were
      significantly faster (P <.01) and maintained working distance significantly
      better (P <.05) than K-Flexofiles. These differences were insignificant in 35
      degrees curved canals. CONCLUSION: Hero 642 instruments prepared curved canals
      rapidly, without change in working length and with only minimal transportation
      toward the outer aspect of the curve.

PMID- 11505271
TI  - Study of the expression of CD68+ macrophages and CD8+ T cells in human granulomas
      and periapical cysts.
AB  - In the periapex, the interaction among inflammatory cells and microorganisms and
      their products results both in specific and nonspecific immune responses. Many
      studies have reported quantitative analysis of the immunocompetent cells in
      periapical lesions, but the exact ratio of these cells in cysts and granulomas
      remains unknown. In the present study, we undertook a quantitative analysis of
      CD68+ cells and CD8+ T cells in human periapical granulomas and cysts.
      Immunoperoxidase staining revealed that CD68+ cells were present in both lesions,
      with no statistically significant difference, mainly distributed in the inner
      portion of the lesion, where the inflammation site is more active. On the other
      hand, CD8+ lymphocytes were more numerous in cysts. Thus, it appears that CD8+ T
      cells may play a more important role in a later phase of periapical lesion
      progression, probably exerting regulatory or cytotoxic functions in cellular
      immune response, which may lead to the stabilization of these lesions.

PMID- 11505272
TI  - Dynamic scintigraphy with thallium-201 chloride (Tl-201) for the diagnosis of
      tumors of the head and neck.
AB  - OBJECTIVE: The purpose of this study was to differentiate between malignant
      tumors and benign tumors of the head and neck by means of thallium-201 chloride
      scintigraphy. STUDY DESIGN: Thallium-201 chloride (Tl-201) scintigraphy and Ga-67
      citrate (Ga-67) scintigraphy were performed in 10 patients with a benign tumor
      and in 90 patients with a malignant tumor. The blood flow index and the tumor
      retention index were obtained by means of Tl-201 scintigraphy. The blood flow
      index = the count of tumor/the count of control in the early dynamic scan from 30
      to 120 seconds after injection, and the tumor retention index = (the count of
      tumor/the count of control in the delayed dynamic scan 2.5 hours after
      injection)/(the count of tumor/the count of control in the early dynamic scan
      from 4 to 5 minutes after injection). RESULTS: The early and delayed scans with
      Tl-201 demonstrated a very high correlation with the blood flow index. The tumor
      retention index had a tendency to increase in malignant tumors, especially in the
      poorly differentiated tumors and the severely invasive tumors. Likewise, the
      tumor retention index decreased in benign tumors. These results proved to be
      statistically significant, and in turn Tl-201 scintigraphy was deemed superior to
      Ga-67 scintigraphy. Tl-201 scintigraphy was also useful in detecting small-size
      tumors. CONCLUSION: The tumor retention index of Tl-201 was useful for the
      differentiation of malignant tumors of the head and neck from benign tumors of
      the same areas.

PMID- 11505273
TI  - The utility of panoramic imaging of the temporomandibular joint in patients with
      temporomandibular disorders.
AB  - OBJECTIVE: The objective of this study was to evaluate the utility of panoramic
      imaging in assessment of patients with temporomandibular disorders (TMDs). STUDY
      DESIGN: Fifty-five consecutive patients referred for diagnosis and management of
      facial pain and jaw dysfunction were included. A single examiner completed the
      history and clinical examination on all patients. All patients received panoramic
      imaging. On the basis of clinical and radiographic findings, a subset of patients
      received advanced imaging modalities. The panoramic radiographs were interpreted
      by 2 examiners; if any disagreement was noted, a third examiner interpreted the
      radiographs. RESULTS: Seventy-five percent of the patients had complaints of
      facial pain, and 75% exhibited tenderness in masticatory muscles. Tenderness was
      present in TM joint regions in 62%. Altered bony anatomy was seen in 43.6% of
      panoramic radiographs. Panoramic imaging did not lead to changes in clinical
      diagnosis in any of the patients seen, although the findings on the radiographs
      did lead to requests for additional imaging studies in 3 cases, one of which was
      later referred for surgical intervention because of radiographic findings.
      CONCLUSION: Clinical findings may be of greater relevance leading to the
      diagnoses associated with TMD and to determination of the need for additional
      imaging rather than the use of panoramic imaging in all patients with facial pain
      and TMD.

PMID- 11505274
TI  - Quantitative analysis of normal major salivary glands using computed tomography.
AB  - OBJECTIVES: We sought to calculate the size and the computed tomography (CT)
      number of normal parotid and submandibular glands and to evaluate their
      relationship with respect to sex, age, and obesity in the Korean population.
      STUDY DESIGN: The authors investigated the axial CT images of 42 healthy
      volunteers. The maximum cross-sectional area (MCSA) was used as an indicator of
      the size of the gland. Three regions of interest on axial scans were selected to
      calculate the mean CT number. RESULTS: There was a significant decrease in the
      mean MCSA of the submandibular gland and the CT number of both glands with age.
      The MCSA of the submandibular gland in males was larger than that in females.
      There was a close correlation between the parotid and the submandibular glands
      with respect to the CT number, as well as between the left and right glands with
      respect to the MCSA and the CT number. The body mass index was positively
      correlated with the MCSA of the parotid gland, whereas the body mass indexes and
      the CT numbers of both glands were negatively correlated. CONCLUSIONS: Both age
      and obesity are closely correlated with the size and the CT number of the major
      salivary glands. Moreover, the correlation between the CT numbers of the parotid
      and the submandibular glands may be used for diagnostic purposes.

PMID- 11505275
TI  - Philadelphia chromosome-negative, bcr/abl-positive chronic myelogenous leukemia.

PMID- 11505276
TI  - The Nobel Prize Centennial 1901-2001: some aspects on Alfred Nobel, the selection
      procedure and a few prizes.

PMID- 11505277
TI  - Tubulointerstitial injury of Thy-1 nephritis in uninephrectomized stroke-prone
      spontaneously hypertensive rats.
AB  - Thy-1 nephritis was induced in stroke-prone spontaneously hypertensive rats (SHR
      SP) with unilateral nephrectomy (UNX) and normotensive same genetic strain Wistar
      Kyoto (WKY) rats with UNX to evaluate whether the tubulointerstitial injury in
      Thy-1 nephritis is accelerated by long-term systemic and intraglomerular
      hypertension. SHR-SP that underwent UNX at twelve weeks of age were randomly
      assigned to receive monoclonal anti-thy 1.1 antibody (group SP), and normal
      saline (group SC). Age-matched normotensive WKY rats served as controls and were
      given the same dose of monoclonal anti-thy 1.1 antibody after UNX (group WK). In
      all groups, the blood pressure and renal function were assessed, and morphologic
      changes of tubulointerstitium were examined by using immunohistochemistry and
      light microscopy twelve weeks after Thy-1 nephritis induction (in groups SP and
      WK) and UNX alone (in group SC). In all groups, histological findings, the degree
      of monocyte/macrophage infiltration, interstitial expression of alpha-smooth
      muscle actin (alpha-SMA), which is a marker for myofibroblasts, and the degree of
      tubular cell proliferation were examined. In addition, assessments of blood
      pressure, serum creatinine and BUN levels, and the degree of proteinuria were
      made. In parallel to glomerular structural damage, interstitial fibrosis with
      predominant monocyte/macrophage influx, increased interstitial expression of
      alpha-SMA and tubular cell proliferation were observed in group SP. A significant
      increase in serum creatinine and proteinuria were also present in this group. In
      contrast, the changes observed in group SC were not so evident or extensive as in
      group SP. The level of proteinuria was lower than that in group SP. No evident
      tubulointerstitial changes were found in group WK. The results showed that
      tubulointerstitial injury was prominently progressed in the hypertensive model
      with Thy-1 nephritis. This suggests that sustained systemic and glomerular
      hypertension is not only ultimately responsible for the progression of
      immunologically mediated glomerular injury, but is also responsible for
      subsequent tubulointerstitial changes. Migration and proliferation of
      myofibroblasts and intense influx of monocytes/macrophages may contribute to the
      development of tubulointerstitial fibrosis.

PMID- 11505278
TI  - An epidemiological study on occupational low back pain among people who work in
      construction.
AB  - People who work at construction sites have one of the highest incidences of low
      back pain (LBP). The purpose of this study is to evaluate the status of LBP, and
      to investigate the risk factors of LBP in construction workers. The subjects were
      33, 530 workers who were sent our questionnaires in September and October 1996.
      Of the final respondents, 29.3% had LBP. The results of multi-regression analysis
      revealed that risk factors having significant relationships with the onset of LBP
      were 1) stress due to personal relations at work, 2) postures during work, and 3)
      unstable body balance on scaffoldings. In addition, two factors were found to be
      important in decreasing the incidence of LBP: 1) having sufficient space for
      taking a rest and 2) using pre-work exercises. These findings have led us to the
      conclusion that not only providing good physical working environments, but also
      giving instructive and psychological care are important in preventing the onset
      of LBP in construction workers.

PMID- 11505279
TI  - Study on the treatment of tracheobronchial stenosis using expandable metallic
      stents.
AB  - The purpose of this study is to clarify the clinical usefulness of Gianturco-Z
      stent (G-Z stent) for the management of malignant and benign tracheobronchial
      stenosis. Seventy-three stents were used in 30 patients. In 20 cases, we used the
      so-called "stent-in-stent" method. Twenty-four patients were grade 5, and 6 were
      grade 4 according to the Hugh-Jones classification of respiratory status. The
      technical success rates, clinical condition, respiratory status, blood gas
      analysis, survival rate, and complications were reviewed on the basis of the
      patients'medical records and radiographs. All stents were successfully placed in
      the appropriate position. After the procedure, respiratory status improved in 97%
      (29/30) of the patients. PaO(2) increased statistically (p<0.05), and PaCO(2)
      decreased one week after the treatment. Mean survival of 30 patients after stent
      placement was 123 days. Mean survival in 9 malignant patients treated in
      combination with radiotherapy (182 days) was statistically longer (p<0.01) than
      in those treated without radiotherapy (65 days, n=20). The tracheobronchial burn
      patient who received a combination of stent placement and post operative
      radiotherapy survived 540 days. No major complications were encountered during or
      after the procedure. Only 3 minor complications were observed: 1 stent migration,
      1 partial rupture of the stent, and 1 stent deformation. G-Z stent treatment with
      the "stent-in-stent" technique is useful for palliation of malignant and benign
      tracheobronchial stenosis, and should contribute to improving the quality of life
      in patients with advanced cancer.

PMID- 11505280
TI  - Two distinct populations of neurons expressing nitric oxide synthase mRNA in the
      female rat preoptic area: site specific changes induced by sex steroids.
AB  - Non-isotopic in situ hybridization histochemistry in the basal forebrain of
      gonadectomized juvenile female rats visualized neuronal nitric oxide synthase
      (nNOS) mRNA in two distinct cellular populations, one in the organum vasculosum
      of the lamina terminals (OVLT) and the other in the rostral preoptic area at the
      level of the anteroventral periventricular nucleus (rPOA). In the rPOA,
      digoxigenin-labeled nNOS mRNA positive cells were in close proximity to the cell
      body of gonadotropin-releasing hormone (GnRH) -immunoreactive neurons. In the
      OVLT, the labeled cells were in an area rich in GnRH fibers. In the frontal
      section of the rPOA, the labeled cells were distributed in an inverted V-shaped
      area over the third ventricle. Combined treatment with estradiol and progesterone
      caused a significant reduction in the number of nNOS mRNA positive cells in the
      inverted V-shaped area in the female rat rPOA. The treatment induced a
      luteinizing hormone surge at the time of sacrifice. In the OVLT, ovarian steroids
      had no effect on nNOS mRNA expression. The results indicate that nNOS mRNA
      expression in the rPOA is regulated by ovarian steroids in a site-specific
      manner.

PMID- 11505281
TI  - High survival rate of 6 cases of pulmonary large cell neuroendocrine carcinoma
      formerly classified as small cell carcinoma.
AB  - In the revised WHO classification of lung cancer, published in 1999, large cell
      neuroendocrine carcinoma (LCNEC) was employed as a new histological entity. LCNEC
      is generally considered a high-grade malignant lung cancer, and appropriate
      treatment remains to be determined. Before its new classification, LCNEC had long
      been classified into several entities. Advancing the review of previous cases in
      Nippon Medical School Hospital, we noticed that some LCNEC patients were formally
      diagnosed as having small cell lung cancer (SCLC), and they showed long-term
      survival. MATERIAL AND METHODS: All histological specimens of surgically resected
      SCLC in Nippon Medical School Hospital were reclassified according to the 1999
      WHO classification manual. Their neuroendocrine differentiations were confirmed
      by the use of immunostainings with chromogranin A and synaptophysin. RESULTS:
      Fourteen cases satisfied the qualifications for both histological and clinical
      reevaluation. Among them, 6 patients were reclassified as LCNEC, and their stage
      distribution was as follow: IA; 1, IB; 2, IIIA; 2, and IIIB; 1. Their survival
      term ranged from 33.8 to 78.0 months; 5 were still alive, and 1 (IIIB) died 57.6
      months after surgery. DISCUSSION: According to this study, all the LCNEC patients
      who were treated as SCLC patients showed more favorable prognoses than patients
      described in published studies, even overall lung cancer. Therefore, it is
      suggested that multimodality therapy for SCLC may improve the prognoses of
      patients with LCNEC.

PMID- 11505282
TI  - Usefulness of bronchoalveolar lavage for the diagnosis and treatment of
      refractory pneumonia in a patient with Kostmann syndrome, a severe congenital
      neutropenia.
AB  - An 11-year-old girl with Kostmann syndrome developed refractory pneumonia.
      Culture of oral discharge, throat-swab specimens, and blood could not identity
      the causative organism, and systemic antimicrobial therapy failed to achieve
      improvement. We then performed diagnostic bronchoalveolar lavage (BAL) and
      culture of BAL fluid (BALF) yielded Pseudomonas aeruginosa. Therapeutic BAL using
      gentamicin produced a striking improvement of her pneumonia. CONCLUSION: In
      immunocompromised children with pneumonia, BAL helps to identify the causative
      organism. If the patient is unresponsive to systemic antimicrobial therapy, BAL
      using antimicrobial agents is also worth trying.

PMID- 11505283
TI  - [The topics of sleep disorder: concerning sleep-wake rhythm disorder].

PMID- 11505284
TI  - Our experience in childhood osteomyelitis.

PMID- 11505285
TI  - Biochemical assessment of cardiac function in patients undergoing surgery for
      gastric cancer.

PMID- 11505286
TI  - [PET - Quo vadis?].

PMID- 11505287
TI  - [Accuracy of positron emission tomography with fluorine-18-fluoro-deoxyglucose].
AB  - BACKGROUND: : FDG-PET is a powerful tool for the diagnostic workup of patients
      with lung cancer. A reduced sensitivity of FDG-PET for the evaluation of lung
      lesions was reported for bronchioloalveolar carcinoma (BAC). No literature exists
      about the diagnostic efficacy of FDG-PET in the staging of BAC. METHODS: : Out of
      a series of subsequent 630 untreated patients with the final diagnosis of lung
      cancer, who underwent FDG-PET, all patients with BAC were evaluated with respect
      to tumour detection, N-staging, and M-staging. RESULTS: : 35 patients (5.6 %) had
      BAC, 22 in a localized form (8 x pT1, 14 x pT2), 13 in a disseminated stage. FDG
      PET correctly identified 19/22 cases with localized forms. Two of the missed one
      were classified as pT1. All disseminated forms of BAC were detected. Standardized
      uptake values (SUV) ranged from 0.9 to 23.3 (mean +/- SD: 11.6 +/- 5.1). Accuracy
      of N-staging was comparable to known results in lung cancer (FDG-PET 80 %, CT 64
      %). With respect to M-staging, sensitivity of FDG-PET was as follows: M1(HEP):
      2/3 (67 %), M1(PUL): 7/8 (88 %), M1(OSS): 1/1 (100 %). CONCLUSIONS: : With some
      limitations in small localized tumours FDG-PET can detect and stage BAC with an
      accuracy which is identical to that for other histological types of non-small
      cell lung cancer.

PMID- 11505288
TI  - [Meta-analysis of the efficacy of positron emission tomography with F-18
      fluorodeoxyglucose in lung tumors. Basis for discussion of the German Consensus
      Conference on PET in Oncology 2000].
AB  - BACKGROUND: : To analyse current literature on FDG-PET for evaluation of lung
      lesions, N-staging, M-staging, and recurrence of lung cancer for the third German
      Consensus Conference on PET in oncology. METHODS: Specialists in nuclear
      medicine, pneumology, radiation oncology, diagnostic radiology, and thoracic
      surgery reviewed the relevant literature as listed in MEDLINE from 1985 to 1999
      for further analysis. Out of the published data cumulative test parameters and
      summary receiver operating characteristic curves (sROC curves) were computed.
      RESULTS: Sensitivity, specificity, and accuracy of FDG-PET are 96 %, 80 %, 91 %
      for evaluating lung lesions (15 studies with at least 35, in total 1144
      patients). With corresponding values of 88 %, 92 %, 91 % (20 studies, 1292
      patients) for N-staging FDG-PET is superior to CT with 65 %, 76 %, 73 % (19
      studies, 1268 patients). With 94 %, 97 %, 96 % (4 studies, 336 patients) M
      staging with FDG-PET is very accurate and changed therapeutic management in 18 %
      of the cases (8 studies, 695 patients), unexpected extrathoracic metastases were
      found in 12 % (7 studies, 581 patients). FDG-PET is the most accurate non
      invasive method to evaluate suspected adrenal metastases (3 studies, 263
      patients, sensitivity 96 %, specificity 99 %, accuracy 98 %). Recurrence is
      detected accurately (4 studies, 224 patients, sensitivity 99 %, specificity 89 %,
      accuracy 95 %). CONCLUSIONS: Studies with in total more than 1000 patients show
      the high diagnostic efficacy of FDG-PET and its superiority to conventional
      imaging in lung cancer. Based on this analysis the third German Consensus
      Conference on PET in oncology evaluated FDG-PET on lung cancer. 1a-indications
      are evaluation of lung nodules in patients at risk for complications during
      surgery, N-staging, M-staging (except brain), and detection of recurrence.

PMID- 11505289
TI  - [Vocal cord dysfunction in children and adolescents].
AB  - More attention has been given to vocal cord dysfunction (VCD) in the past years.
      Even though the disease is known since 1983 and was brought to mind at least
      casuistically through the years, often VCD was not diagnosed as such, being
      mistaken for bronchial asthma - at times with grave consequences for the patient.
      VCD causes the acute onset of stridulous respiration with acute dyspnea making
      the differential diagnosis of asthma quite suggestive. The inspirational stridor
      and a peracute progression of the disease should cause doubts as to the diagnosis
      of asthma. We collected case reports and describe the symptoms and diagnostic
      approaches to VCD as well as showing discriminating findings towards bronchial
      asthma. We report on five children suffering from VCD (4 girls, 1 boy) aged from
      2 to 13 years. It could be shown that VCD is caused by a multifactoral
      pathomechanism, which has both somatic and psychological aspects. A surprising
      find was that all of the children were diagnosed with a pathological
      gastroesophageal reflux, partly in serious dimensions, without showing the
      typical symptoms such as retrosternal pain, stomach-ache or recurrent vomiting
      (so called silent reflux). Since there is a multitude of pathomechanisms involved
      and the disease often coincides with allergic asthma, an individual therapy plan
      is needed for each patient.

PMID- 11505290
TI  - [Usefulness of stress echocardiography for early diagnosis of anthracycline
      induced cardiomyopathy].
AB  - BACKGROUND: Early evidence of drug induced cardiomyopathy is of great importance
      in oncological treatment, especially for application of Anthrazyklines. Stress
      echocar-diography (SE) has been proven to be of value in determining left
      ventricular function at rest and under stress. This study was performed to
      investigate the cardiac function under Anthrazykline-chemotherapy (aCT). PATIENTS
      AND METHODS: Patients with malignant thoracic tumors and indication for aCT
      underwent pharmacological SE (infusion of increasing dobutamin-doses, 5
      microgram/kg/bw in 3 minute-steps) before starting aCT. Left ventricular ejection
      fraction (LVEF) and wall motion were measured. If the tumor decreased and the
      patients underwent 4 or more cycles of CT, at the end of the last CT another SE
      investigation was performed. RESULTS: 30 patients (20 men, 15 women; mean age 52,
      range 28 - 71) were included and the data were compared. Before aCT the mean LVEF
      was 59 % at rest and 71 % at maximum load, no disturbances of wall motion could
      be observed. After the end of aCT (mean dose 408 mg, range 256 - 549; mean 4.4
      cycles, range 4 - 7) the LVEF was 58 at rest and 68 at maximum load (not
      significant) and there were also no disturbances of motion. CONCLUSION: SE is an
      alternative to echocardiography at rest in assessment of left ventricular
      function in patients receiving Anthrazykline-CT. With the doses applied no
      patient developed cardiomyopathy. So we consider SE a cost-effective method and
      safe for patients.

PMID- 11505291
TI  - [Genetics of the neuronal NO synthase (NOS1) in the etiology of bronchial
      asthma].
AB  - The free radical nitric oxide (NO) is endogenously produced by enzymes known as
      NO synthases. NO in the airways is involved in a number of pathophysiological
      processes, such as airway inflammation, allergic reactions, and asthma. Asthma is
      a multifactorial disease that is caused by environmental and genetic factors.
      Genome wide screening approaches in families revealed evidence for linkage
      between chromosomal region 12q and allergic diseases, increased serum IgE levels
      as well as the development of asthma. The gene encoding for neuronal NOS (NOS1)
      is an attractive candidate gene for asthma, not only because it is localized in
      chromosomal region 12q24. Experimental studies in animals and humans suggest that
      NOS1 plays an important role in asthma. For instance, in a murine model of
      allergic asthma, NOS1 has been shown to be important for the development of
      bronchial hyperresponsiveness, since mice deficient for the nos1 gene were less
      responsive to airway challenge than both wild-type mice and mice deficient for
      the nos2 gene. Case-control studies in humans revealed allelic associations
      between polymorphic markers in the NOS1 gene and the diagnosis of asthma.
      Furthermore, increased concentrations of NO in the airways of asthmatics are
      closely related to the size of an intronic (AAT)(n)-repeat polymorphism in the
      NOS1 gene. The purpose of this review is to summarize studies that provide
      evidence for an involvement of NOS1 in the genetics of asthma.

PMID- 11505292
TI  - [Lung and heart-lung transplantation. Guidelines for indications and preoperative
      diagnosis].

PMID- 11505293
TI  - [Psychosomatic Research in Intensive Care Units - A Systematic Review]
AB  - After a brief historical introduction the literature that has appeared on
      psychosomatic research in intensive care units since the middle fifties is
      reviewed. The main focus in published studies is directed towards subjects like
      the patients and their specific diseases as fatal illness or coronary heart
      disease as well as family needs and interpersonal assessment of staff members.
      Results show the importance of helpful and considerate way of working among staff
      members to reduce stress. Supervision is recommended and supportive psychotherapy
      for patients with severe emotional distress are suggested.

PMID- 11505294
TI  - [Central Relationship Patterns in Comparison with Different Objects]
AB  - In the present study the Relationship Episode Paradigm Interviews of 70 female
      patients with different psychoneurotic diseases were analysed with respect to
      object-specific patterns with the CCRT method. The most frequent categories are
      the same in all relationship episodes and in subsamples of relationship episodes
      with mother and father. These categories are also predominant in episodes with
      women and men. Relationship episodes with mother do not differ from episodes with
      father, and relationship episodes with women do not differ from episodes with
      men. But there are substantial differences in relationship episodes with the
      mother and women and between episodes with the father and men. Patients recount
      much more positive relationship patterns with women and men than with their
      parents. This could be understood as a hint of interpersonal resources.

PMID- 11505295
TI  - [The Duren Vocational Retraining Centre Projects MARQUISA and EVASA]

PMID- 11505296
TI  - [Return to work].

PMID- 11505297
TI  - [Therapeutic programmes focusing on job related problems - which psychosomatic
      patients should participate?].
AB  - The necessity to offer special therapeutic programmes focusing on job related
      problems in psychosomatic rehabilitation has become increasingly evident. Which
      patients should participate in such programmes? This question has not yet been
      discussed with regard to its theoretical and methodological implications. In
      clinical practice the decision has been based on the therapists evaluation. 105
      patients, consecutively admitted in a psychosomatic hospital were interviewed
      with a screening questionnaire about their job related strains and the perceived
      interaction between symptomatology and job. According to the literature
      guidelines for inclusion of psychosomatic patients to a special work hardening
      programme were used. Therapists were asked to independently assign their patients
      to the programme. The overlap between the two procedures was small. While the
      guidelines focussed on a high level of job strain and the patient's motivation
      for a job-related therapeutic approach, the therapists' decision was based on
      duration of inability to work, impairments at work due to the symptoms, conflicts
      with colleagues at work and the patient's ability to perceive problems in a
      differentiated manner. Considering the problem of inclusion-criteria for a work
      hardening programme, the highly complex constellations behind routine therapeutic
      decisions in psychosomatic rehabilitation became evident. To integrate medical
      diagnosis, symptomatology, psychological models, job strain, the patient's social
      situation and values, is a neglected but important goal of rehabilitation
      sciences and should be a base for a concept guiding the development, evaluation
      and establishment of work related therapeutic programmes.

PMID- 11505298
TI  - [Predictors of return to work after inpatient cardiac rehabilitation under
      workers' compensation plan].
AB  - Vocational reintegration is one of the major goals of cardiac rehabilitation. 70
      % of blue-collar workers under 50 years of age resume their job after in-patient
      cardiac rehabilitation. 10 % are hindered to do so by cardiac problems. Specific
      measures exist that may facilitate work resumption. As these measures should be
      started as soon as possible there is a need for predictors of return to work
      which can be obtained easily and at an early stage. Subjects of this prospective
      study were 650 patients (10 % female) under 50 years of age who participated in
      an in-patient cardiac rehabilitation programme under the workers' pension
      insurance scheme. At the beginning of programme participation, problems in work
      resumption as expected by the patient and by his physician were obtained, as well
      as depression and anxiety scores (HADS-D). Physicians' and patients' expectations
      concerning problems in resuming work turn out to be significant predictors of the
      vocational situation of the male patients six months following medical
      rehabilitation. The depression score obtained at the outset of the programme is
      the only predictor of return to work in female patients.

PMID- 11505299
TI  - [Multiperspective estimates on the probability of patient return to work
      following orthopaedic rehabilitation: findings and predictive relevance].
AB  - This article analyses various methods of predicting whether patients in
      orthopaedic rehabilitation will return to work. In this regard, items of
      patients, physicians in charge of rehabilitation and general practitioners have
      been collected and compared to working time lost due to illness. In total, 72 %
      of patients had successfully returned to work after one year. The patients whose
      reintegration could not be achieved could be identified best by asking if they
      believed that they would be in a position to work until the statutory retirement
      age (96 % identified) on the one hand and on the other hand by the physicians'
      estimate as to the degree the last gainful activity might be resumed (90 %
      identified). In this context, the criteria have to be laid down very
      restrictively in order to sufficiently filter out patients not likely to return
      to work. The patients likely to return to work are identified best by means of
      the following characteristics: lack of intention to retire early (96 %
      identified), planning to return to work directly after rehabilitation (88 %
      identified), and little working time lost due to illness prior to rehab (86 %
      identified). In general, a major percentage of patients not likely to return to
      work can be identified by these statements of patients and physicians. The
      statements of general practitioners are clearly less valuable for prediction and
      show only weak correlation with the respective statements of the physicians in
      charge of rehabilitation.

PMID- 11505300
TI  - [Severely disabled employees and their experiences with corporate policies
      concerning job retention. Selected results of an empirical study].
AB  - While the public has been paying attention to the topics illness and disability
      with respect to public health, long-term care insurance and public old age
      insurance systems for years, the risk of becoming disabled at work has been
      considered less. Research in this area has for a long time been focused on
      questions regarding first-time entry and return to work of disabled persons into
      the regular labour market. Also, much policy research has tended to deny an
      active role of the enterprise as an independent player and creator of policy in
      the management of disability. Hence only little documentation of employers'
      programmes and strategies as well as analysis concerning the question of job
      retention is available. In order to cover the research deficit a study with
      regard to employment careers of severely disabled was conducted in Rhineland
      Palatinate from 1997 to 1999. The study pursues two different paths: On the one
      hand living and working conditions of this group are analysed, on the other the
      study's purpose is to give an overview of employers' disability management
      practices from the severely disabled employees' point of view. This article deals
      with the results of the policies within the enterprise study. It concerns the
      analysis of the following issues: Does disability have a negative impact on the
      employees' careers? Which measures are preferred by the persons interviewed and
      why? The final question, whether the need for supporting measures ascertained may
      be satisfied by the existing instruments available under the German Severely
      Disabled Persons Act must be answered with a clear "No"! Employers and disabled
      employees need alternative measures of support.

PMID- 11505301
TI  - [The importance of company interests in shaping occupational rehabilitation
      programs: empirical findings from company-based retraining].
AB  - The pilot project "Occupational Rehabilitation of Women Close to their Place of
      Residence" is orientated towards the dual system of vocational retraining by
      combining "on the job training" and "vocational theory in a vocational training
      school". Training on the job is one of the most important aspects in this
      programme, and data have therefore been gained from qualitative interviews with
      representatives of different firms. The results presented are based on the
      analysis of qualitative interviews with 13 employers involved in the pilot
      project. All interviewees underline: Training on the job alongside non-disabled
      persons is thought to offer good opportunities for lasting vocational integration
      since it enables trainees to grow accustomed to the conditions and demands of
      work and is thought likely to lead directly to employment. We discussed a range
      of mechanisms through which a societal obligation to train and/or employ disabled
      people could be implemented and highlighted the role of "rehabilitation services"
      which support the trainee by psychological, educational and social services and
      support the employer.

PMID- 11505302
TI  - [Company approaches concerning workers with performance alterations or
      disablement: interview findings on the perspectives of the various parties
      involved].
AB  - This paper provides information about the research programme "In-plant
      interventions in the German car industry to increase job opportunities for
      employees with (severe) disabilities". The research was done in 2000 by the
      University of Trier and the International Research Unit for Work and Social
      Integration (IFASI). The purpose of the study was to capture, document, and
      analyse internal practices of occupational rehabilitation in five German car
      factories. Taking a qualitative approach, 23 persons of different company areas
      were interviewed, and numerous documents were analysed. The article reflects
      applied disability management strategies and points out success factors and
      barriers of inclusion.

PMID- 11505304
TI  - ["Patient education, the bridge between research and practice", working
      conference of the Bavarian rehab science network in cooperation with the trans
      network "patient education working group" within the "rehabilitation sciences"
      research funding programme of the federal research ministry, bmbf, and the German
      pension insurance Schema, Oct. 5-6, 2000 in Wurzburg].

PMID- 11505303
TI  - [Community based vocational rehabilitation of women with special regard to the
      use of teletutoring].

PMID- 11505305
TI  - [The road toward unifying rehabilitation law. An interdisciplinary perspective of
      demands on a book 9 of the German social code-33rd practician' seminar of the
      Bochum University Institute of social law, Nov. 11, 2000].

PMID- 11505306
TI  - Investing in emergent literacy intervention: a key role for speech-language
      pathologists.
AB  - Emergent literacy is a developmental period that is receiving renewed and
      increased emphasis in the fields of education and speech-language pathology
      because of its influence on the later literacy development and achievement of
      students. With their strong background in language, language development, and
      language disorders, speech-language pathologists (SLPs) can make significant
      contributions to the acquisition of emergent literacy skills. This article
      focuses on SLP direct-service roles for students with identified communication
      impairments and on indirect roles of assisting teachers and others to promote the
      emergent literacy skills of all students. In addition to the acknowledged
      importance of general oral language, guidelines, suggestions, and resources are
      offered to foster emergent literacy skills in five specific areas: (1) early
      phonological awareness, (2) joint book reading and sense of story, (3) alphabetic
      letter knowledge, (4) adult modeling of literacy activities, and (5) experience
      with writing materials.

PMID- 11505307
TI  - The role of the speech-language pathologist in improving decoding skills.
AB  - In this article, we consider the processes and knowledge involved in decoding and
      present some instructional guidelines and suggestions for teaching students the
      skills necessary for proficient and fluent word reading. The roles and
      responsibilities of speech-language pathologists (SLPs) are also considered. It
      may have been enough several years ago for SLPs to focus solely on early literacy
      skills and phonological awareness. This is not the case today. SLPs not only need
      to collaborate with teachers to develop a comprehensive approach to literacy, but
      also should be providing direct, explicit instruction of decoding skills for
      students with language and learning disabilities.

PMID- 11505308
TI  - Reading comprehension: a language intervention target from early childhood
      through adolescence.
AB  - Speech-language pathologists (SLPs) play an important role in helping children
      and adolescents with language impairments to construct meaning from spoken and
      written language. They work in collaboration with other professionals and
      families to provide the optimal learning experiences and to introduce strategies
      for seeking meaning and monitoring understanding. This article describes language
      intervention techniques to enhance reading comprehension, including the
      development and enhancement of background knowledge and schemata, vocabulary,
      knowledge of text structure, and strategy use. The discussion includes
      suggestions for young children who are developing language comprehension, as well
      as for elementary students and secondary students who comprehend text with
      increasing independence.

PMID- 11505309
TI  - Spelling and the speech-language pathologist: there's more than meets the eye.
AB  - Interest in spelling and spelling difficulties has increased in recent years.
      Like reading, spelling is no longer viewed as a strictly visual process. Rather,
      the language basis of spelling is evident in the phonological, orthographic,
      morphological, and even syntactic knowledge required to be a good speller. Speech
      language pathologists (SLPs) have expertise in basic language processes that
      enable them to play an important role in assessment and intervention for spelling
      problems. Underscoring the importance of this effort are the serious social and
      vocational consequences attached to poor spelling and the intractable nature of
      spelling problems. This article reviews information about spelling-language
      connections, the nature of spelling problems, and assessment and intervention
      principles or procedures that represent best practices based on current spelling
      research. Implications for SLPs working with students who have spelling
      difficulties are suggested throughout.

PMID- 11505310
TI  - The speech-language pathologist's role in a writing lab approach.
AB  - In a writing lab approach, speech-language pathologists (SLPs) work on
      collaborative teams with general and special educators to foster language growth
      using inclusive, curriculum-based, computer-supported writing process
      instruction. By engaging students in authentic writing projects using recursive
      writing processes--planning, organizing, drafting, revising, editing, publishing,
      presenting--and supporting them with instructional scaffolding, peer feedback,
      and computers, SLPs can address individualized needs while achieving goals of the
      general education curriculum. Case examples illustrate how intervention can be
      designed to meet the needs of students with diverse disabilities to interact
      socially and progress academically within the general education curriculum.

PMID- 11505311
TI  - Emergent and early literacy interventions for students with severe communication
      impairments.
AB  - Speech-language pathologists (SLPs) can play a pivotal role in fostering the
      acquisition of literacy skills in students using augmentative and alternative
      communication (AAC). SLPs have unique skills in the areas of vocabulary
      development, phonological processing, selection of graphical symbol systems, and
      knowledge of strategies for facilitating interactive communication. SLPs can
      support parents in providing meaningful emergent literacy activities, and they
      can extend or initiate classroom literacy learning with interventions. This
      article presents some of the literacy difficulties experienced by students with
      severe communication impairments and suggests strategies that SLPs can use to
      support emergent and early literacy in children who use AAC.

PMID- 11505312
TI  - New or expanded literacy roles for speech-language pathologists: making it happen
      in the schools.
AB  - As speech-language pathologists (SLPs) working with children and youth are
      challenged to assume new or expanded roles with reading and writing, those SLPs
      practicing in the schools face specific barriers for doing so. These obstacles
      take two forms: individual inhibitors, involving specific people, and system
      inhibitors, involving the organization at various levels. To overcome these
      barriers, SLPs need to be proactive and take charge of their own destinies by
      engaging in specific actions to assume these new or expanded literacy roles. They
      need to make it happen by using specific tools at their disposal to influence
      others. These tools include marketing, effective communication, and negotiation.

PMID- 11505313
TI  - The history of coronary artery surgery -- a brief review.

PMID- 11505314
TI  - 3D evaluation of myocardial edema: experimental study on 22 pigs using magnetic
      resonance and tissue analysis.
AB  - BACKGROUND: Myocardial edema (ME) adversely affects ventricular function. Thus,
      we performed an animal study to demonstrate (1) 3D-ME using magnetic resonance
      imaging (MRI), which can show ME depending on myocardial location, (2) type of
      cardioplegic solution, and (3) quantification tools. METHODS: Pig hearts (n = 22)
      were perfused using Bretschneider's solution (BRET, n = 8), butanedionemonoxime
      (BDM, n=8), or no cardioplegia as controls (CTRL, n = 6). Hearts underwent MRI
      (T(1)-inversion recovery). Myocardial water content (MWC, reference method) was
      determined from left ventricle anterior, posterior (PW), lateral wall,
      interventricular septum, papillary muscle, right ventricle wall. Images underwent
      3D reconstruction using ray-tracing. Gray-value analysis was performed on
      "virtual" samples. For statistical analysis, ANOVA, Student's t-test, and the
      Student-Newman-Keuls test were used. RESULTS: (1) ME was induced (p < 0.0001 vs.
      control). Localization differed in MWC, p = 0.003 (BRET), p = 0.023 (BDM),
      highest at PW (p < 0.01). (2) Differences between the cardioplegia groups were
      not significant. (3) "Virtual" samples showed equal distribution (BRET: p =
      0.007, BDM: p = 0.003), highest at PW (p < 0.01). CONCLUSIONS: We validated 3D
      assessment of induced ME in pig hearts using MRI. The method may therefore become
      an exact tool in monitoring cardioplegia.

PMID- 11505315
TI  - In vitro modelling of tissue using isolated vascular cells on a synthetic
      collagen matrix as a substitute for heart valves.
AB  - BACKGROUND: Tissue engineering is a promising approach for obtaining lifetime
      durability in biological heart valves. Basic questions with respect to the
      selection of suitable cell populations as well as scaffolds remain unsolved. The
      purpose of this study was to develop a tissue-like substitute in vitro for
      replacement of diseased valves in vivo. METHODS: Smooth-muscle cells (SMCs) were
      isolated from human and porcine aortic tissue using the 'explant technique' and
      endothelial cells from collagenase digestion. Seeding and cultivation of isolated
      cells was performed on a type-I collagen matrix. The scaffold-cell specimen was
      investigated using light and electron microscopy. Cupromeronic blue and
      immunoprecipitation were used for ultracytochemical staining. RESULTS: SMCs were
      allowed to grow to multilayers and migrate into the collagen network. We found a
      tissue-like morphology in these samples characterised by several layers of cells,
      spaces between the cell layers filled with newly formed extracellular matrix
      components, compartmentalisation of proteoglycans and their association with
      fibrilar matrix and the cell surface. Endothelium cells covered the SMCs of the
      scaffold with a histological topography similar to heart valves. CONCLUSIONS:
      This is an approach for in vitro modelling of tissue-like substitutes and
      preparing plane multicellular tissues as substitutes for heart valves. This model
      may also be used for cell biological investigations of cell-matrix interactions.

PMID- 11505316
TI  - Correction of tetralogy of Fallot: does the time period of surgery influence the
      outcome?
AB  - BACKGROUND: The perioperative outcome of patients with tetralogy of Fallot (TOF)
      seems to have improved over the last four decades. METHODS: To prove this
      hypothesis, we retrospectively analysed the data of 269 TOF patients operated on
      between 1975 and 1999 in our institution. RESULTS: Over the years, younger
      patients (median age 1975 - 1980: 4.5 years, 1995 - 1999: 0.9 years) were
      operated on with a lower mortality (1975 - 1980: 8.6 %, 1995 - 1999: 2.4 %).
      Residual defects such as pulmonary stenosis or insufficiency and VSD occurred
      with a similar frequency over time, whereas rhythm disturbances were
      significantly reduced (1981 - 1985: 51.2 %, 1995 - 1999: 24.4 %, p = 0.012).
      Postoperative length of hospital stay was significantly (p < 0.05) shorter in the
      years 1995 - 1999 (11.0 - 11.4 days) than in 1975 - 1980 (16.9 +/- 16.5 days).
      CONCLUSIONS: Over time periods, there was a trend towards lower mortality and
      towards operating on patients in a younger age. The rate of rhythm disturbances
      and the LOS after surgery proved to be reduced during the last decade. These
      differences did not turn out to be statistically significant. Therefore, we
      conclude that the time period of surgery has only little impact on the early
      outcome of patients after definitive correction of TOF.

PMID- 11505317
TI  - The effect of nutritional status on morbidity in COPD patients undergoing
      bilateral lung reduction surgery.
AB  - BACKGROUND: Although candidates for lung reduction surgery (LRS) include
      malnourished patients with severe chronic obstructive pulmonary disease (COPD),
      the impact of preoperative nutritional status on surgical outcome has not been
      clearly elucidated. METHODS: We investigated the relationship between
      preoperative nutritional status and postoperative morbidity in 23 consecutive
      patients undergoing LRS. The percentage of ideal body weight (%IBW) and body mass
      index (BMI) were calculated, and fat-free mass (FFM) and fat mass (FM) were
      measured using a bioelectrical impedance analyzer. FFM and FM were expressed as
      height-normalized indices, FFM index [FFM (kg)/height (m)(2), or FFMI] and FM
      index [FM (kg)/height (m)(2), or FMI]. Serum levels of total protein and albumin
      were also determined. RESULTS: 8 patients had major complications. Preoperative
      %IBW and FFMI were significantly lower among patients with major complications,
      while no significant differences were observed in pulmonary function, FMI or
      serum protein. The complication rate was significantly higher among patients with
      low FFMI (FFMI < or = 16) but not with low %IBW or BMI. CONCLUSION: These results
      suggest that FFM depletion is an excellent predictor of unacceptable
      postoperative complication following LRS.

PMID- 11505318
TI  - Optimal cell source for cardiovascular tissue engineering: venous vs. aortic
      human myofibroblasts.
AB  - Arterial vascular cells have been successfully utilized for tissue engineering in
      human cardiovascular structures, such as heart valves. The present study
      evaluates saphenous vein-derived myofibroblasts as an alternative, easy-to-access
      cell source for human cardiovascular tissue engineering. Biodegradable
      polyurethane scaffolds were seeded with human vascular myofibroblasts. Group A
      consisted of scaffolds seeded with cells from ascending aortic tissue; in group
      B, saphenous vein-derived cells were used. Analysis included histology, electron
      microscopy, mechanical testing, and biochemical assays for cell proliferation
      (DNA) and extracellular matrix (collagen). DNA content was comparable in both
      groups. Collagen and stress at maximum load was significantly higher in group B.
      Morphology showed viable, layered cellular tissue in all samples, with collagen
      fibrils most pronounced in group B. In conclusion, saphenous vein myofibroblasts
      cultured on biodegradable scaffolds showed excellent in vitro tissue generation.
      Collagen formation and mechanical properties were superior to aortic tissue
      derived constructs. Therefore, the easy-to-access vein cells represent a
      promising alternative cell source for cardiovascular tissue engineering.

PMID- 11505319
TI  - Higher hematocrit improves liver blood flow and metabolism during cardiopulmonary
      bypass in piglets.
AB  - OBJECTIVES: Hemodilution has been applied conventionally during cardiopulmonary
      bypass (CPB) and deep hypothermic circulatory arrest (DHCA) to counteract the
      increase in viscosity and deleterious rheological effects caused by hypothermia.
      However, liver dysfunction after low-flow bypass and DHCA is common, and little
      is known about the effects of hematocrit (Hct). The purpose of the present study
      is to evaluate the impact of two hemodilution priming protocols used clinically
      on liver perfusion and metabolism. MATERIALS AND METHODS: Ten piglets were
      randomized into 2 groups. One group (n = 5) had a crystalloid prime resulting in
      an Hct of about 15 % (low hematocrit; group L), the other (n = 5) a total-blood
      prime (Hct = 25 %; high hematocrit; group H). All animals underwent 70 min
      cooling at full flow (150 ml/kg/min), 30 min of low flow (50 ml/kg/min) at 15
      degrees C followed by 45 min of DHCA and 75 min of rewarming at full flow. Liver
      blood flow (LBF) was assessed at the beginning of CPB at 34 degrees C, at the end
      of cooling at 15 degrees C, at the end of low flow, 5 min after the start of
      warming, and at the end of rewarming at 34 degrees C by injections of radioactive
      microspheres. Liver function was evaluated at the same time using the MEGX test,
      which measures the metabolism of lidocaine. RESULTS: LBF was insignificantly
      reduced during cooling, decreased during low flow (p = 0.001), and increased
      again after DHCA with the highest flow at the end of rewarming. LBF tended to be
      lower at all times in group L (p = 0.096). The liver lidocaine metabolic rate did
      not significantly decrease during cooling and low flow, but was increased at the
      end of rewarming (p = 0.01); the metabolism was higher in group H (p = 0.025).
      Multiregression analysis revealed liver blood flow (p = 0.003) and hematocrit (p
      < 0.001) as independent determinants of the liver lidocaine metabolism; arterial
      blood pressure and temperature did not have significant influence in this model.
      CONCLUSION: Hemodilution results in a tendency towards reduced liver blood flow
      during CPB; much worse is the resulting impaired liver metabolism, independent of
      reduced blood flow and pressure. Avoidance of low hematocrit during CPB may be a
      useful adjunct to preserve liver function in patients undergoing cardiac surgery
      with long duration CPB and DHCA.

PMID- 11505320
TI  - Bronchial repair with pulmonary preservation for severe blunt trauma.
AB  - After a motorcycle accident, a 22-year-old male was diagnosed with multiple rib
      fractures, left-sided tension pneumothorax, hemothorax and left upper lobe
      bronchus rupture at its origin. An emergency left thoracotomy revealed an almost
      complete avulsion of the upper lobe bronchus from the main stem bronchus, a
      severely damaged pulmonary artery, and a concurrent deep intraparenchymal lower
      lobe laceration. Since the patient was hemodynamically stable, a decision was
      made to preserve as much lung as possible. In the event of complex pulmonary
      trauma, pulmonary preservation is desirable since emergency pneumonectomy is
      usually associated with high mortality. Early bronchoscopic assessment, careful
      anesthetic management, and meticulous surgical technique with liberal use of
      fibrin glue were crucial to successful outcome.

PMID- 11505321
TI  - A case of repetitive intrapleural cancer chemotherapy using INFUSE-A-PORT for
      malignant mesothelioma.
AB  - A 57-year-old man was diagnosed as having malignant pleural mesothelioma. We
      placed an implantable reservoir (INFUSE-A-PORT) into his pleural cavity to
      administer repetitive intrapleural chemotherapy. We administered intrapleural
      chemotherapy 7 times over a period of 10 months. The progression of the disease
      was very gradual; he could continue working during this time. INFUSE-A-PORT may
      be useful for repetitive intrapleural chemotherapy in outpatient treatment of
      malignant mesothelioma.

PMID- 11505322
TI  - Carinal leiomyoma: report of a case treated by carinal resection and
      reconstruction.
AB  - Here, we present a case report on a young female patient with a carinal
      leiomyoma. The patient complained of progressive dyspnea and paroxysmal cough.
      The laminagram and bronchoscopy revealed a lobulated carinal tumor, and carinal
      resection and reconstruction were performed. In this report, we will emphasize
      the appropriate surgical treatment for this condition.

PMID- 11505323
TI  - Intrathoracic free musculocutaneous flap after open-window thoracostomy for
      chronic empyema.
AB  - An 85-year-old man was suffering from right pyothorax caused by methicillin
      resistant staphylococcus aureus (MRSA). The empyema cavity was closed by
      intrathoracic implantation of a free rectus abdominis musculocutaneous (MC) flap
      using microvascular surgery 2 months after open-window thoracostomy (OWT).
      Compared with a pedicled MC flap, a free flap has the advantage that it can close
      a larger empyema cavity since the whole flap can be inserted into the cavity.
      Although the use of a free MC flap requires a two-stage operation, this method is
      believed to be more successful for controlling chronic empyema than any other
      established procedure, including decortication, thoracoplasty or
      pleuropneumonectomy.

PMID- 11505324
TI  - Modification of surgical aortoatrial shunts for inaccessible bleeding in aortic
      surgery -- modification of the Cabrol-shunt technique.
AB  - Bleeding after complex ascending aortic, aortic root or transverse arch surgery
      which is inaccessible or difficult to control may present a major problem. Here,
      we describe a modified Cabrol-shunt technique using complete mediastinal coverage
      with decompression into the innominate vein where the classical technique is not
      suitable. The long-term fate of the classical aortoatrial and modified
      mediastinal to innominate shunts has been analyzed to assess their potential
      complications.

PMID- 11505325
TI  - Surgical management of a penetrated greenfield inferior vena cava filter.
AB  - This is a case report of an IVC filter penetration identified during lymph-node
      dissection for endometrial carcinoma. Although the spread strut put the adjacent
      abdominal aorta in danger of penetration, surgical removal of the filter could
      not be performed because there was still an increased risk of pulmonary embolism.
      Instead of IVC interruption, we used a wrapping technique as a prophylaxis
      against major bleeding complication due to IVC filter dislocation and recurrent
      pulmonary embolism.

PMID- 11505326
TI  - Proximalized lateral tunnel for the bypass to the dorsalis pedis artery -- a safe
      way to go.
AB  - BACKGROUND: Wound complications associated with bypass grafting to the dorsalis
      pedis artery are frequent, and threaten the viability of the bypass and the limb.
      METHODS: The long saphenous vein can be tunneled from its bed down the lateral
      side of the anterior margin of the tibia for subsequent anastomosis with the
      dorsalis pedis artery. CONCLUSION: The proximalized lateral tunnel for the bypass
      to the dorsalis pedis artery has the advantage of protecting the bypass graft
      from exposure if the patient develops wound breakdown.

PMID- 11505327
TI  - Neuroprotection in aortic surgery.
AB  - Operations on the aortic arch still remain a great challenge for cardiac surgeons
      and necessitate a period of cerebral blood flow interruption. lt is therefore
      imperative to protect the brain during this very sensitive time. Clinical as well
      as experimental studies have shown that the exact mechanism of neural injury
      seems to be multifactorial. Furthermore it is still uncertain, whether cerebral
      injury occurs during the interval of HCA or during reperfusion. Various
      strategies have been adopted in an effort to reduce neurological complications
      after aortic surgery. These included the use of hypothermic circulatory arrest,
      antegrade cerebral perfusion and retrograde cerebral perfusion. All these methods
      have both advantages and disadvantages. New surgical techniques such as cold
      reperfusion have shown promising results in animal experiments and need further
      clinical evaluation. One very promising pathway in preventing cerebral injury
      lies in pharmacological interventions.

PMID- 11505328
TI  - "Looking into the past only makes sense if it serves the future." Konrad Adenauer
      (1876 - 1967).

PMID- 11505329
TI  - Risk scores currently used in German heart surgery.
AB  - BACKGROUND: Risk scores (RS) in heart surgery assess mortality and morbidity and
      mirror the degree of severity of disease of the patients when presented for
      surgery. We examined the use and dissemination of RS in Germany. MATERIAL AND
      METHODS: Our survey included 79 German heart surgery institutes in Fall 1999 and
      Winter 2000. RESULTS: Four institutes did not respond. Out of 75 (ad 100 %)
      responders 56 (75 %) institutes did not use RS, 17 (22 %) institutes used one RS
      method and 2 (3 %) institutes used two RS methods. The most frequently applied RS
      methods were the Cleveland Clinic Score and the Euro Score (n = 7, each) followed
      by institution-specific, internally developed RS methods (n = 5), Parsonnet's RS
      (n = 1) and the RS from the STS database (n = 1). Fourteen institutes used RS for
      internal quality control. Of these, 2 institutes publish their RS data for
      external quality control. The patient-related individual procedure risk was used
      in 6 institutes. CONCLUSIONS: A quarter of the German heart surgery institutes
      use one or more RS methods. The most commonly used were the Cleveland Clinic
      Score and the Euro Score, followed by internally developed RS methods. RS methods
      were most frequently used for internal quality control. The degree of the
      severity of disease of the patients who presented for surgery could only be
      compared between a small number of institutes using the same RS.

PMID- 11505330
TI  - Short-term changes in Helicobacter pylori gastritis and bulbitis during and after
      2 weeks of treatment with omeprazole and amoxicillin in duodenal ulcer patients.
AB  - OBJECTIVE: To evaluate the dynamics of histological changes in the mucosa of the
      stomach and duodenal bulb during and after completion of a 14-day course of Hp
      eradication dual treatment with high-dose omeprazole and amoxicillin. PATIENTS:
      12 patients (mean age 53 +/- 16 years SD, 9 male, 3 female) with an acute Hp
      positive duodenal ulcer were included in this open, prospective, single-centre
      study. METHOD: Patients were given omeprazole 40 mg b.i.d. and amoxicillin 1,500
      mg b.i.d. for a period of 14 days. Endoscopic biopsies were obtained on days 3,
      7, 14, 28, 42 as well as at following endoscopies performed a mean of 17 months
      after treatment. RESULTS: The Hp-eradication rate achieved 4 weeks after
      treatment was 82%. On day 14, 88% of the ulcers were healed. Already on day 7 Hp
      had almost completely disappeared from the antrum, corpus and duodenal bulb, and
      the activity of gastritis in the antrum and corpus and the activity of bulbitis
      in the duodenal bulb was almost nonexistent. The decrease in the grade of
      gastritis was much lower by day 42. CONCLUSIONS: Our study shows for the first
      time that in all patients signs of primarily successful Hp-eradication treatment
      during the first days of treatment are consistently demonstrable and complete
      already after one week of therapy, irrespective of the subsequent cure or
      persistence of Hp-infection. In the patients with persistence of Hp-infection Hp
      colonization and activity of gastritis quickly increased within 2-4 weeks after
      cessation of treatment. Checks to evaluate complete eradication or recrudescence
      of Hp-infection should be carried out not earlier than 28 days after cessation of
      treatment.

PMID- 11505331
TI  - [A plant extract and its modified preparation in functional dyspepsia. Results of
      a double-blind placebo controlled comparative study].
AB  - AIMS: To assess the efficacy and safety of the commercially available herbal
      preparation (Iberogast, STW-5*) containing extracts from bitter candy tuft,
      chamomile flower, peppermint leaves, caraway fruit, licorice root, lemon balm
      leaves, angelica root, celandine herbs, milk thistle fruit and its research
      preparation STW-5-S (without bitter candy tuft) in patients with functional
      dyspepsia. PATIENTS AND METHODS: After a standardized diagnostic work-up and at
      least 7 days free of medication, 60 patients, diagnosed with functional
      dyspepsia, were recruited in a multicenter trial and randomly assigned to one of
      3 treatment groups (STW-5, STW-5-S or placebo). Each patient received the
      treatment for 4 weeks. The main outcome variables were the improvement of a
      gastrointestinal symptom score (GIS), a sumscore consisted of 10 dyspeptic
      symptoms rated on a Likert scale. Dyspeptic symptoms were assessed at baseline, 2
      and 4 weeks after treatment. RESULTS: 60 patients completed the trial (mean age
      46.8 years, range 25-70, female 38 patients). Compared with placebo-group both
      herbal preparations STW-5 and STW-5-S showed a clinically significant improvement
      of GIS after 2 and 4 weeks of treatment (p < 0.001). No statistically significant
      difference could be observed between the efficacy of STW-5 and STW-5 S (p >
      0.05), but a solid improvement of gastrointestinal symptoms could be achieved
      earlier with STW-5 than with its research preparation STW-5-S without bitter
      candy tuft (p = 0.023). CONCLUSIONS: In patients with functional dyspepsia, the
      commercially available herbal preparation STW-5 and its modified dispense STW-5-S
      tested improved dyspeptic symptoms significantly better than placebo. The extract
      bitter candy tuft appeared to have an additive effect on dyspeptic symptoms.

PMID- 11505332
TI  - Cholestatic hepatitis A complicated by acute renal insufficiency.
AB  - 31 cases of non-fulminant hepatitis A complicated by acute renal insufficiency
      are reported in the literature. Two-thirds of those patients needed dialysis,
      usually when depending on the severity of their hyperbilirubinemia. This report
      concerns the first published case of non-fulminant cholestatic hepatitis A
      complicated by acute renal insufficiency in which a spontaneous remission of
      renal function occurred without need for dialysis despite a very severe
      hyperbilirubinemia.

PMID- 11505333
TI  - [Therapy of abdominal and thoracic chylous effusions 18 years after radiation
      therapy].
AB  - Chylothorax and chylascites are rare complications of neoplasm or surgical, but
      also non-surgical trauma. Extremely rare causes are a subclavian i.v. line, a
      mesenterical hamartoma, retrosternal goiter, liver cirrhosis, portal vein
      thrombosis, filariasis, tuberculosis, ruptured aortic aneurysm and radiotherapy.
      We report on a 60-year-old male with bilateral chylothorax and chylascites
      resistant to therapy 18 years after irradiation of the iliacal, paraaortal and
      mediastinal (46 Gray) and the left-sided supraclavicular (40 Gray) lymph nodes
      for a seminoma (T3N1M0 i.e. IIa, Lugano classification). A fat-free parenteral
      nutrition was started in order to bring the lymphatic flow down to a minimum.
      Chyle flow ceased after 3 1/2 weeks of treatment. An oral diet with middle chain
      triglycerides (MCT-diet), which are transported to the liver via the portal vein
      instead of the lymphatic system, achieved good control of residual chylous
      effusions.

PMID- 11505334
TI  - Helicobacter pylori-negative gastric ulcerations associated with celiac disease
      at first presentation.
AB  - Ulcers of the small bowel have repeatedly been described as a late complication
      of celiac disease and they are considered a signum mali ominis. We report a case
      of a 53-year-old woman presenting with diarrhea, epigastric pain and abdominal
      distensions for a period of few weeks. At upper GI endoscopy, biopsies were taken
      showing complete atrophy of the villi and colonization of the small bowel mucosa.
      Additionally, uncommon multilocular peptic ulcers were seen in the gastric
      antrum. These ulcers proved to be Helicobacter pylori-negative with no evidence
      of Zollinger-Ellison syndrome. Biopsies of gastric ulcers showed signs of a
      lymphocytic gastritis with an extensive infiltration of the lamina propria by
      almost exclusively CD3- and CD45R0-positive T-lymphocytes. Intraepithelial T
      lymphocytes were found to be increased in the antral as well as the corpus
      mucosa. Typing the patient for human leukocyte antigens showed a DQA1*0501 and
      DQB1*0201 phenotype. According to the present report, gastric peptic ulcers seem
      to be another phenomenon associated with celiac disease. In the case presented
      here, ulcers were diagnosed together with celiac disease already at first
      presentation of the patient.

PMID- 11505335
TI  - [Hereditary hemorrhagic telangiectasia (Osler-Rendu-Weber disease) and its
      manifestation in the liver].
AB  - M. Osler (Hereditary Hemorrhagic Telangiectasia, HHT) is an autosomal dominant
      inherited disease, with various vascular malformations. The genetic cause of this
      disease lies in different defects of transmembrane proteins (endoglin, activin
      receptor like-kinase 1) that can be defined as components of the receptor complex
      for transforming growth factor beta (TGF beta). Vascular malformations include
      the gastrointestinal tract and especially the liver. The location of mutations
      encoding hepatic involvement of M. Osler still remains unknown. These vascular
      malformations may lead to different shunts in the liver and can result to
      different complications like cardiac-insufficiency, portal hypertension and
      hepatic encephalopathy in adulthood. Color Doppler sonography is the method of
      choice for screening patients with M. Osler--suspected of having hepatic
      involvement. As in rare events conservative treatment of complications of hepatic
      involvement fail, embolization of the hepatic artery as minimal invasive therapy,
      surgical ligation of the A. hepatica and liver transplantation are possible
      treatment options. As there are only limited experiences with these therapeutic
      procedures patients with liver involvement should be treated at a center, where
      all therapy options are available.

PMID- 11505336
TI  - [Functional dyspepsia: philosopher's stone or much noise about nothing?].
AB  - Does it make sense to diagnose functional dyspepsia? In 1998, a committee
      gathered in Rome recommended to diagnose functional dyspepsia in patients with
      persistent or recurrent pain or discomfort centered in the upper abdomen but no
      disease likely to explain the symptoms, which are not exclusively relieved by
      defecation or associated with changed stool frequency or form. Careful history
      taking, physical examination and upper endoscopy during a symptomatic period off
      anti-secretory therapy are recommended as minimum workup. Functional dyspepsia
      thus is a diagnosis of exclusion. The term is unfortunate: It suggests the
      presence of a manifest or yet covert organ dysfunction and also a fundamental
      difference between disorders with defined and with unknown cause, only the former
      being serious. However, that a limited number of investigations failed to reveal
      a cause does not mean that there is no cause. Further, functional often is used
      synonymous with vague and ideology-ridden terms such as "organ neurosis",
      "vegetative dystonia" and "psychosomatic disorder". There are no unequivocal data
      showing that patients with functional dyspepsia share pathophysiological,
      psychosocial or psychopathological characteristics or that there is a specific
      therapy. In the individual patient, therapy has to be tailored according to the
      symptoms. It thus seems doubtful whether the diagnosis functional dyspepsia can,
      for a patient's treatment or otherwise, be of value. If a categorization is
      deemed inevitable, the term idiopathic dyspepsia would be preferable, as it
      unequivocally makes clear that the symptoms' cause is unrevealed.

PMID- 11505337
TI  - [Therapy of chronic hepatitis C with pegylated interferon alfa-2a].

PMID- 11505338
TI  - The promoter of a lysosomal membrane transporter gene, CTNS, binds Sp-1, shares
      sequences with the promoter of an adjacent gene, CARKL, and causes cystinosis if
      mutated in a critical region.
AB  - Although >55 CTNS mutations occur in patients with the lysosomal storage disorder
      cystinosis, no regulatory mutations have been reported, because the promoter has
      not been defined. Using CAT reporter constructs of sequences 5' to the CTNS
      coding sequence, we identified the CTNS promoter as the region encompassing
      nucleotides -316 to +1 with respect to the transcription start site. This region
      contains an Sp-1 regulatory element (GGCGGCG) at positions -299 to -293, which
      binds authentic Sp-1, as shown by electrophoretic-mobility-shift assays. Three
      patients exhibited mutations in the CTNS promoter. One patient with nephropathic
      cystinosis carried a -295 G-->C substitution disrupting the Sp-1 motif, whereas
      two patients with ocular cystinosis displayed a -303 G-->T substitution in one
      case and a -303 T insertion in the other case. Each mutation drastically reduced
      CAT activity when inserted into a reporter construct. Moreover, each failed
      either to cause a mobility shift when exposed to nuclear extract or to compete
      with the normal oligonucleotide's mobility shift. The CTNS promoter region shares
      41 nucleotides with the promoter region of an adjacent gene of unknown function,
      CARKL, whose start site is 501 bp from the CTNS start site. However, the
      patients' CTNS promoter mutations have no effect on CARKL promoter activity.
      These findings suggest that the CTNS promoter region should be examined in
      patients with cystinosis who have fewer than two coding-sequence mutations.

PMID- 11505339
TI  - Novel TFAP2B mutations that cause Char syndrome provide a genotype-phenotype
      correlation.
AB  - To elucidate further the role, in normal development and in disease pathogenesis,
      of TFAP2B, a transcription factor expressed in neuroectoderm, we studied eight
      patients with Char syndrome and their families. Four novel mutations were
      identified, three residing in the basic domain, which is responsible for DNA
      binding, and a fourth affecting a conserved PY motif in the transactivation
      domain. Functional analyses of the four mutants disclosed that two, R225C and
      R225S, failed to bind target sequence in vitro and that all four had dominant
      negative effects when expressed in eukaryotic cells. Our present findings,
      combined with data about two previously identified TFAP2B mutations, show that
      dominant negative effects consistently appear to be involved in the etiology of
      Char syndrome. Affected individuals in the family with the PY motif mutation,
      P62R, had a high prevalence of patent ductus arteriosus but had only mild
      abnormalities of facial features and no apparent hand anomalies, a phenotype
      different from that associated with the five basic domain mutations. This
      genotype-phenotype correlation supports the existence of TFAP2 coactivators that
      have tissue specificity and are important for ductal development but less
      critical for craniofacial and limb development.

PMID- 11505340
TI  - Toward a better understanding of the metabolic effects of ischemic
      preconditioning in humans.

PMID- 11505341
TI  - Myocardial lactate production is not involved in the ischemic preconditioning
      mechanism in coronary artery bypass graft surgery patients.
AB  - OBJECTIVE: To study the relationship between ischemic preconditioning (IP) and
      lactate production and their impact on coronary artery bypass graft surgery
      patients. DESIGN: Prospective, randomized, controlled study. SETTING: University
      hospital. PARTICIPANTS: Eighty 3-vessel disease coronary artery bypass graft
      surgery patients with stable and unstable angina pectoris. INTERVENTIONS: The IP
      patients were preconditioned with 2 periods of 2-minute ischemia followed by 3
      minute reperfusion before aortic cross-clamping. MEASUREMENTS AND MAIN RESULTS:
      The cardiac index (CI) after surgery was significantly higher in the IP group
      than in controls among stable patients (p = 0.013). IP was not effective in CI
      recovery in unstable patients. The baseline values of lactate production were
      11.6%, 20.3%, -7.0%, and -2.9% in stable IP, stable control, unstable IP, and
      unstable control patients. Compared with baseline, lactate production increased
      significantly after the IP protocol (39.0% and 47.5% in the stable and unstable
      patients), and operation (47.5%, 31.7%, 35.4%, and 35.6% in stable IP, stable
      control, unstable IP, and unstable control patients) but not after 10 minutes of
      cardiopulmonary bypass (29.7% and 19.0% in the stable and unstable patients).
      There were no differences among the groups in lactate production after the
      operation. Lactate production after the IP protocol was negatively associated
      with CI recovery after surgery in the IP patients (p = 0.026). CONCLUSION: The IP
      effects do not include modulation of lactate production. IP induces lactate
      production, but it seems not to be involved in the triggering process.

PMID- 11505342
TI  - Does isoflurane optimize myocardial protection during cardiopulmonary bypass?
AB  - OBJECTIVE: To investigate the possible myocardial protective effect of isoflurane
      during aortic cross-clamp and cardioplegic cardiac arrest in patients undergoing
      conventional coronary artery bypass graft surgery. DESIGN: Prospective,
      randomized. SETTING: University medical center. PARTICIPANTS: Forty-nine patients
      undergoing elective coronary artery bypass graft surgery divided into 2 groups:
      control group (n = 21) and isoflurane group (n = 28). INTERVENTION: Isoflurane
      was administered in the pre-cardiopulmonary bypass (CPB) period to the isoflurane
      group. MEASUREMENTS AND MAIN RESULTS: Hemodynamics and ST- segment variations
      were monitored in the pre-CPB period and after weaning from CPB in both groups.
      Incidence of reperfusion arrhythmias after release of aortic cross-clamp was
      compared. In the isoflurane group, the mean cardiac index after CPB was
      significantly higher than the pre-CPB value, whereas no difference between the 2
      values was found in the control group. The higher cardiac index in the isoflurane
      group was associated with a lesser degree of ST- segment changes than in the
      control group. There was no significant difference between the 2 groups in the
      incidence of reperfusion arrhythmias after release of aortic cross-clamp.
      CONCLUSION: The present report suggests that administration of isoflurane before
      aortic cross-clamping in patients undergoing coronary artery bypass graft surgery
      may optimize the myocardial protective effect of cardioplegia. Isoflurane may be
      particularly advantageous whenever prolonged periods of aortic cross-clamping or
      inadequate delivery of cardioplegia is expected.

PMID- 11505343
TI  - Hemin, inducer of heme-oxygenase 1, improves functional recovery from myocardial
      stunning in conscious dogs.
AB  - OBJECTIVE: To examine the effects of pretreatment with hemin, an inducer of the
      potential antioxidative enzyme heme-oxygenase 1 (HO-1) or heat-shock protein 32,
      on myocardial stunning. DESIGN: Randomized animal study. SETTING: Animal
      laboratory of a university hospital. PARTICIPANTS: Chronically instrumented
      mongrel dogs (n = 44). INTERVENTIONS: Dogs underwent chronic instrumentation for
      measurement of hemodynamics and myocardial wall thickening fraction (WTF).
      Experiments with 12 dogs were performed on separate days in a crossover fashion:
      (1) 10 minutes of left anterior descending (LAD) coronary artery occlusion after
      application of hemin (9 mg/kg/d) for 1 week and (2) 10 minutes of LAD coronary
      artery occlusion without hemin pretreatment. In control experiments (n = 32), the
      reversible induction of HO-1, using gel electrophoresis and Western blotting, was
      determined. MEASUREMENTS AND MAIN RESULTS: WTF was measured as a baseline value
      before hemin administration and at predetermined time points until complete
      recovery from stunning. LAD artery occlusion caused a significant reduction in
      the WTF in the LAD-perfused area with and without hemin, without significant
      hemodynamic changes. At all time points, after 1 minute of reperfusion, the WTF
      as percentage of baseline values was significantly higher after hemin
      pretreatment (p < 0.05). Baseline WTF values were reached after 24 hours with and
      after >48 hours without hemin pretreatment (p < 0.05). CONCLUSION: Hemin
      pretreatment attenuates myocardial stunning in conscious dogs.

PMID- 11505344
TI  - Impact of off-pump coronary artery surgery on myocardial performance and beta
      adrenoceptor function.
AB  - OBJECTIVE: To determine the hemodynamic changes during beating heart
      revascularization of the left anterior descending artery, the circumflex artery,
      and the right coronary artery as well as cardiovascular beta-adrenoceptor
      function before and after off-pump coronary artery bypass surgery. DESIGN:
      Prospective study. SETTING: University department of cardiothoracic anesthesia.
      PARTICIPANTS: Twenty patients scheduled for off-pump coronary artery bypass
      surgery using the Octopus 2 stabilizer system. INTERVENTIONS: Isoproterenol, 4
      microg, was administered intravenously after induction of anesthesia and again
      after surgery to monitor cardiac beta-receptor function. MEASUREMENTS AND MAIN
      RESULTS: The hemodynamic responses to isoproterenol and cardiovascular variables
      were monitored before, during, and after immobilization of the target coronary
      artery with catheters in the radial and pulmonary arteries. During surgery on the
      left anterior descending artery (n = 23), stroke volume and cardiac index
      decreased 17 mL (21%) and 400 mL (17%). During revascularization of the
      circumflex artery (n = 9), stroke volume and cardiac index decreased 19 mL (28%)
      and 300 mL (17%). During surgery on the posterior aspect of the heart (n = 13),
      stroke volume and cardiac index decreased 22 mL (29%) and 400 mL (17%). All the
      cardiovascular variables had returned to baseline values 5 minutes after
      releasing the heart. The hemodynamic responses to isoproterenol were equal before
      and after surgery. CONCLUSION: This study provides evidence that the hemodynamic
      changes associated with off-pump surgery on the 3 major coronary arteries are
      similar and of short duration. No desensitization of cardiovascular beta
      adrenoceptors was found. This finding is in contrast to the deterioration in beta
      adrenoceptor function seen after surgery with cardiopulmonary bypass.

PMID- 11505345
TI  - Occurrence of myocardial ischemia immediately after coronary revascularization
      using radial arterial conduits.
AB  - OBJECTIVE: To assess the incidence of myocardial ischemia in patients receiving
      radial arterial and left internal thoracic arterial conduits (RA+LITA) during the
      postrevascularization period. DESIGN: Nonrandomized observational sequential
      cohort. SETTING: University hospital. PARTICIPANTS: Thirty adult patients,
      scheduled for elective coronary artery bypass graft surgery with RA+LITA,
      compared with 30 patients who received saphenous vein graft and left internal
      thoracic arterial conduits. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS:
      Myocardial ischemic episodes were defined as reversible ST-segment depressions or
      elevations >or=1 mm and >or=2 mm at J +60 msec and lasting >or=1 minute using 2
      channel Holter monitoring. During the post-cardiopulmonary bypass period, a
      significantly higher number of patients with >or=2 mm ischemic episodes (21.7%; p
      = 0.015) and higher number of >or=2 mm ischemic episodes per hour (0.19 +/- 0.4
      episodes/hr; p = 0.03) were observed in the radial artery group versus the
      comparison group (0% of patients and 0 episodes/hr). During the postoperative
      period (24 hours), a significantly longer duration of >or=2 mm ischemic episodes
      was observed in the radial artery group (24 +/- 33 minutes v 8.4 +/- 21 minutes;
      p = 0.046). Radial artery graft, preoperative calcium antagonists, and pulmonary
      arterial mean pressure were independent predictors of the duration and area under
      the ST-segment curve of >or=2 mm ischemic episodes during the postoperative
      period. CONCLUSION: There is an association between the use of the radial artery
      graft and the incidence and severity of >or=2 mm postrevascularization ischemic
      episodes.

PMID- 11505346
TI  - Early extubation after cardiac surgery: emotional status in the early
      postoperative period.
AB  - OBJECTIVE: To compare the emotional state during the first 3 days after coronary
      artery surgery of patients who had undergone early versus conventional
      extubation. DESIGN: A prospective, randomized, controlled trial. SETTING:
      University hospital, single center. PARTICIPANTS: Eligible patients (n = 100)
      presenting for elective coronary artery surgery, randomized to an early
      extubation group or a conventional extubation group. INTERVENTIONS: Emotional
      status was measured by the Hospital Anxiety and Depression Scale (HAD), the Self
      Assessment Manikin (SAM), and the Multiple Affect Adjective Check List-Revised
      (MAACL-R). Tests were administered preoperatively and on the 1st and 3rd days
      postoperatively. MEASUREMENTS AND MAIN RESULTS: Of patients in the conventional
      extubation group, 30% showed moderate-to-severe depressive symptoms (HAD score
      >10) on day 3 postoperatively compared with 8% of patients in the early
      extubation group (p = 0.02). There was a clinically insignificant increase in
      MAACL-R depression score on the 1st postoperative day within both groups but no
      other differences within or between groups in SAM or MAACL-R scores. CONCLUSION:
      Early extubation results in fewer patients displaying depressive symptoms on the
      3rd postoperative day but appears to have little effect on other measurements of
      emotional status. Anesthetic management during coronary artery bypass graft
      surgery may play an important role in the overall well-being of the patient by
      decreasing the incidence of postoperative depression.

PMID- 11505347
TI  - Target-controlled infusion or manually controlled infusion of propofol in high
      risk patients with severely reduced left ventricular function.
AB  - OBJECTIVE: To compare hemodynamics, time to extubation, and costs of target
      controlled infusion (TCI) with manually controlled infusion (MCI) of propofol in
      high-risk cardiac surgery patients. DESIGN: Prospective, randomized. SETTING:
      Major community university-affiliated hospital. PARTICIPANTS: Twenty patients
      undergoing first-time implantation of a cardioverter-defibrillator with severely
      reduced left ventricular function (left ventricular ejection fraction <30%).
      INTERVENTIONS: Anesthesia was performed using remifentanil, 0.2 to 0.3
      microg/kg/min, and propofol. Propofol was used as TCI (plasma target
      concentration, 2 to 3 microg x mL; n = 10) or MCI (2.5 to 3.5 mg/kg/hr; n = 10).
      MEASUREMENTS AND MAIN RESULTS: Hemodynamics were measured at 6 data points: T1,
      before anesthesia; T2, after intubation; T3, after skin incision; T4, after first
      defibrillation; T5, after third defibrillation; and T6, after extubation. There
      were no significant hemodynamic differences between the 2 groups. Dobutamine was
      required to maintain cardiac index >2 L/min/m(2) in significantly more patients
      of the TCI group than of the MCI group. Mean dose of propofol was higher in the
      TCI patients (6.0 +/- 1.0 mg/kg/hr) than in the MCI patients (3.0 +/- 0.4
      mg/kg/hr) (p < 0.05), whereas doses of remifentanil did not differ. Time to
      extubation was significantly shorter in the MCI (11.9 +/- 2.4 min) versus the TCI
      group (15.6 +/- 6.8 min). Costs were significantly lower in MCI patients (34.73
      dollars) than in TCI patients (44.76 dollars). CONCLUSIONS: In patients with
      severely reduced left ventricular function, TCI and MCI of propofol in
      combination with remifentanil showed similar hemodynamics. TCI patients needed
      inotropic support more often than MCI-treated patients. Although extubation time
      was longer in TCI patients and costs were higher, both anesthesia techniques can
      be recommended for early extubation after implantation of a cardioverter
      defibrillator.

PMID- 11505348
TI  - Endotoxin-neutralizing capacity of serum from cardiac surgical patients.
AB  - OBJECTIVE: To determine if endotoxin core antibody (EndoCAb) from the serum of
      cardiac surgical patients neutralizes endotoxin in an ex vivo biologic assay.
      DESIGN: Prospective blinded cohort study. SETTING: Academic medical center.
      PARTICIPANTS: Patients (n = 203) undergoing cardiac surgery. INTERVENTIONS: Sera
      were obtained from patients preoperatively. MEASUREMENTS AND MAIN RESULTS:
      EndoCAb levels were determined by enzyme-linked immunosorbent assay. Sera were
      incubated for 15 minutes at 37 degrees C with varying concentrations of endotoxin
      from a clinically relevant bacterium (Escherichia coli serotype O18), then tested
      for the presence of endotoxin activity using the validated Limulus amebocyte
      lysate assay. Median (interquartile range) IgM and IgG EndoCAb levels were 118
      median units (range, 31 to 259 median units) and 208 median units (range, 108 to
      401 medium units). Increasing levels of IgM EndoCAb were associated with
      increased neutralization of endotoxin (p < 0.0001). Increasing levels of IgG
      EndoCAb were associated with increased neutralization of endotoxin (p < 0.0001).
      An additive effect of IgM and IgG EndoCAb levels on endotoxin neutralization was
      observed without evidence of synergistic or plateau effects. EndoCAb levels did
      not completely predict serum neutralization capacity. CONCLUSION: Anti-EndoCAbs
      of both classes (IgM and IgG) were able to neutralize lipopolysaccharide from a
      clinically relevant bacterium in an ex vivo model. Neither Igm nor IgG appeared
      to be more capable of neutralization in this model. These antibodies did not
      completely predict neutralization capacity; other endogenous factors in human
      serum must be capable of lipopolysaccharide neutralization.

PMID- 11505350
TI  - Liver transplantation without venovenous bypass: morbidity and mortality in
      patients with greater than 50% reduction in cardiac output after vena cava
      clamping.
AB  - OBJECTIVE: To investigate whether a decrease in cardiac output of >or=50% after
      vena cava clamping is associated with an increase in perioperative morbidity or
      mortality in patients undergoing orthotopic liver transplantation without
      venovenous bypass. DESIGN: Retrospective, clinical study. PARTICIPANTS: Patients
      undergoing elective orthotopic liver transplantation without venovenous bypass (n
      = 172). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In 82 patients (group
      1), the decrease in cardiac output after vena cava clamping was >or=50%; in 90
      patients (group 2), the decrease was <50%. Hemodynamics during surgery and
      perioperative morbidity and mortality were compared between group 1 and group 2
      patients. Mean arterial pressure during the anhepatic phase was not significantly
      different between groups, but cardiac output and mixed venous oxygen saturation
      were significantly lower in group 1 patients. Perioperative mortality, need for
      postoperative renal replacement therapy, postoperative serum creatinine levels,
      and graft function were not different between groups. CONCLUSION: A >50%
      reduction in cardiac output after vena cava clamping is not associated with an
      increase in perioperative morbidity and mortality when compared with patients
      with a less pronounced reduction in cardiac output. These results question the
      common practice of basing the indication for venovenous bypass during the
      anhepatic phase on a reduction in cardiac output of >50% after a trial of vena
      cava clamping.

PMID- 11505349
TI  - Anti-inflammatory effects of 17beta-estradiol pretreatment in men after coronary
      artery surgery.
AB  - OBJECTIVE: To investigate the anti-inflammatory and hemodynamic effects of 17beta
      estradiol in men undergoing elective coronary artery bypass graft surgery (CABG).
      DESIGN: Prospective, randomized, controlled. SETTING: Operating room and
      intensive care unit in a university hospital. PARTICIPANTS: Twenty-one men
      undergoing primary, elective CABG surgery. INTERVENTION: 17beta-estradiol, 2mg,
      was given orally twice in 14 hours before the operation. MEASUREMENTS AND MAIN
      RESULTS: Leukocyte counts, plasma myeloperoxidase, tumor necrosis factor-alpha,
      interleukin (IL)-6, IL-8, and IL-10 were measured perioperatively. Leukocyte
      counts were lower in the 17beta-estradiol group than in controls at 6 hours (11.4
      +/- 2.0 hours v 15.5 +/- 4.7 hours x 10(9)/L) and 20 hours (11.6 +/- 1.9 hours v
      13.6 +/- 2.5 hours x 10(9)/L) after reperfusion (p = 0.03). The release of
      myeloperoxidase was lower in the 17beta-estradiol group than in controls (5
      minutes; 634.4 +/- 213.1 microg/mL v 773.1 +/- 209.3 microg/mL; 4 hours, 305.0 +/
      108.0 microg/mL v 441.3 +/- 191.6 microg/mL; p = 0.02). Systemic vascular
      resistance index was lower just after cardiopulmonary bypass, and cardiac index
      was higher postoperatively in the 17beta-estradiol group as compared with
      controls. CONCLUSION: Pretreatment with 17beta-estradiol can limit leukocyte
      activation in men after CABG surgery.

PMID- 11505351
TI  - Application of modified sequential organ failure assessment score in children
      after cardiac surgery.
AB  - OBJECTIVE: To evaluate the usefulness of the modified sequential organ failure
      assessment (m/SOFA) score for assessing morbidity and mortality in pediatric
      patients after cardiac surgery. DESIGN: Analysis of a prospectively collected
      database. SETTING: Pediatric intensive care unit of a university-affiliated
      hospital. PARTICIPANTS: Consecutive pediatric patients (n = 142) undergoing
      cardiac surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The m/SOFA
      score, consisting of 5 organ scores (maximum score of 20 points), was calculated
      on admission (initial) and at 12 and 36 hours postoperatively. An initial score
      of >5 points with an unchanged or upward postoperative trend predicted a higher
      postoperative mortality and a greater need for intensive care intervention. In
      neonates, sustained higher score >10 points predicted an outcome of death with a
      sensitivity of 100% and a specificity of 87%. Given the higher mortality related
      to immature organ function and a greater complexity of heart defects, the
      application of the m/SOFA score, a less invasive and simple way to assess organ
      damage, is especially suitable in neonates. The m/SOFA score would be more
      appropriately assessed according to the congenital heart defect or surgical
      procedure because the types of cardiac defect after the surgical repair affect
      each organ score measurement. CONCLUSION: Application of the m/SOFA score in the
      early postoperative period, which reflects cumulative perioperative organ damage,
      would provide some direction to eventual outcomes of morbidity and mortality in
      patients with congenital heart defects undergoing surgery.

PMID- 11505353
TI  - Combined aortic valve replacement and orthotopic liver transplantation.

PMID- 11505352
TI  - Effect of C1-esterase-inhibitor on capillary leak and inflammatory response
      syndrome during arterial switch operations in neonates.
AB  - OBJECTIVE: To determine if prophylactic administration of C1-esterase-inhibitor
      would have a beneficial effect on postoperative weight gain and the inflammatory
      response in neonates undergoing cardiac surgery with cardiopulmonary bypass
      (CPB). DESIGN: Randomized, double-blinded study. SETTING: University-affiliated
      heart center. PARTICIPANTS: Twenty-four neonates with transposition of the great
      arteries. INTERVENTIONS: In group inhibitor (INH) patients (n = 12), 100 IU/kg of
      C1-esterase-inhibitor (Berinert) was given 30 minutes before CPB. In group
      placebo (P) patients (n = 12), placebo was administered instead. Interleukin (IL)
      6, C3a anaphylatoxin, C1 activity, prekallikrein, Hageman factor, D-dimers, and
      clinical parameters were measured 6 times perioperatively. MEASUREMENTS AND MAIN
      RESULTS: All 24 patients had an uneventful clinical course. Mean arterial
      pressure and pulmonary oxygenation after CPB were superior in group INH patients.
      The weight gain on postoperative days 1 to 4 was significantly less in group INH
      patients compared with group P (55 +/- 59 g vs. 340 +/- 121 g, day 1). The
      concentration of IL-6 (76 +/- 17 pg/mL vs. 262 +/- 95 pg/mL during CPB) was
      significantly lower in group INH patients compared with group P patients. In
      contrast, no influence on C3a anaphylatoxin and coagulation factors was found.
      CONCLUSION: Prophylactic application of C1-esterase-inhibitor in neonates
      undergoing arterial switch operations produces less inflammatory response
      compared with placebo. This difference may have contributed to improved clinical
      parameters, including less weight gain postoperatively.

PMID- 11505354
TI  - Use of femoral-femoral cardiopulmonary bypass for urgent aortic valve replacement
      in a patient with critical aortic stenosis and left ventricular dysfunction.

PMID- 11505355
TI  - Acute pulmonary edema after percutaneous balloon valvuloplasty for pulmonary
      valve stenosis.

PMID- 11505356
TI  - Fresh whole blood and immunoglobulin permit coronary artery bypass graft surgery
      in patients with idiopathic thrombocytopenic purpura.

PMID- 11505357
TI  - Myocardial dysfunction in septic shock: Part II. Role of cytokines and nitric
      oxide.

PMID- 11505358
TI  - Case 7--2001. Management during cardiopulmonary bypass of patients with presumed
      fish allergy.

PMID- 11505359
TI  - Pro: Postmenopausal hormone replacement therapy improves outcome in women
      undergoing coronary artery bypass graft surgery.

PMID- 11505360
TI  - Con: Postmenopausal hormone replacement therapy does not improve outcome in women
      undergoing coronary artery bypass graft surgery.

PMID- 11505361
TI  - Blood return after Veress needle placement for left-sided thoracoscopy.

PMID- 11505362
TI  - Unexpected transesophageal echocardiogram finding during an aortic valve
      replacement.

PMID- 11505363
TI  - Heat preservation during cardiac surgery.

PMID- 11505365
TI  - Does carotid sinus baroreceptor dysfunction increase vasopressor drug
      requirements after combined carotid and coronary artery surgery?

PMID- 11505366
TI  - Cardiac morphology and blood pressure in the adult zebrafish.
AB  - Zebrafish has become a popular model for the study of cardiovascular development.
      We performed morphologic analysis on 3 months postfertilization zebrafish hearts
      (n > or = 20) with scanning electron microscopy, hematoxylin and eosin staining
      and Masson's trichrome staining, and morphometric analysis on cell organelles
      with transmission electron photomicrographs. We measured atrial, ventricular,
      ventral, and dorsal aortic blood pressures (n > or = 5) with a servonull system.
      The atrioventricular orifice was positioned on the dorsomedial side of the
      anterior ventricle, surmounted by the single-chambered atrium. The
      atrioventricular valve was free of tension apparati but supported by papillary
      bands to prevent retrograde flow. The ventricle was spanned with fine trabeculae
      perpendicular to the compact layer and perforated with a subepicardial network of
      coronary arteries, which originated from the efferent branchial arteries by means
      of the main coronary vessel. Ventricular myocytes were larger than those in the
      atrium (P < 0.05) with abundant mitochondria close to the sarcolemmal.
      Sarcoplasmic reticulum was sparse in zebrafish ventricle. Bulbus arteriosus was
      located anterior to the ventricle, and functioned as an elastic reservoir to
      absorb the rapid rise of pressure during ventricular contraction. The dense
      matrix of collagen interspersed across the entire bulbus arteriosus exemplified
      the characteristics of vasculature smooth muscle. There were pressure gradients
      from atrium to ventricle, and from ventral to dorsal aorta, indicating that the
      valves and the branchial arteries, respectively, were points of resistance to
      blood flow. These data serve as a framework for structure-function investigations
      of the zebrafish cardiovascular system.

PMID- 11505367
TI  - Expression of connexin43 in mouse Leydig, Sertoli, and germinal cells at
      different stages of postnatal development.
AB  - Connexin 43 (Cx43) is the most abundant and ubiquitously distributed gap junction
      protein in testicular cells. Lack of Cx43 expression results in male infertility.
      We investigated whether Cx43 is expressed and regulated in Leydig, Sertoli and
      germinal cells at different stages of postnatal development. Cx43 was detected
      using three different antibodies shown by immunoblotting to be highly specific.
      At different postnatal ages Cx43 localization was compared in serial or double
      labeled testicular cryosections with immunocytochemical distribution of
      steroidogenic enzyme, 3 betahydroxysteroid-dehydrogenase (3betaHSD), Mullerian
      inhibitory hormone (MIH), and germinal nuclear cell antigen (GNCA1), which are
      specific markers of interstitial Leydig, Sertoli and germinal cells,
      respectively. In the interstitium, round cell clumps (RCC) with lipid droplets
      positive for 3betaHSD and Cx43 were frequently found at intertubular areas at
      birth and Cx43 was mainly localized at cell membrane appositions. From day 3, the
      number and size of 3betaHSD-positive RCC started to decrease, and reached a
      minimum at 7-14 dpp; Cx43 expressed by them is progressively downregulated. From
      day 21 an increase in the size and number of RCC positive for Cx43 and 3betaHSD
      was found that continued at 24, 26 and 28 days and reached a maximum at 35 and 60
      dpp. Biphasic expression of interstitial Cx43 and 3betaHSD was also found to be
      positively and temporally correlated with fluctuations in intratesticular
      testosterone content at all ages studied. In the seminiferous cord (SC), Cx43 was
      expressed at birth between adjacent Sertoli cells (MIH positive) localized at the
      periphery, as well as in their cytoplasm projections that surround centrally
      localized gonocytes. From days 3 to 7, Cx43 labeling increased in Sertoli cells
      mainly at their apical border. At day 14, Cx43 distribution in Sertoli cells
      changed from apical to basal in parallel to migration of germinal (GNCA1
      positive) cells from the periphery to the center of the SC. At all these ages,
      Cx43 was also localized at cell borders between Sertoli and germinal cells. In
      conclusion, this study demonstrates that Cx43 in Leydig cells is regulated during
      postnatal development in an age and functional dependent manner. In the tubule,
      it is demonstrated that Cx43 is modulated in Sertoli cells during the neonatal
      and prepubertal period. We also provide evidence for the first time that Cx43-gap
      junctions communicate between Sertoli and germinal cells before and during the
      first wave of spermatogenesis.

PMID- 11505368
TI  - Ultracytochemical study of medullary bone calcification in estrogen injected male
      Japanese quail.
AB  - Fine structural and cytochemical studies were performed to clarify the pattern of
      medullary bone calcification, specifically in relation to sulfated
      glycosaminoglycans, by using estrogen-induced medullary bone of male Japanese
      quails. Tibiae were collected at 4 and 7 days after estrogen treatment. Medullary
      bone had developed inward toward the marrow cavity, and calcification had begun
      near the cortical bone and deeper parts of the trabeculae, accompanied by wide
      osteoid at extending tips and surface areas of the trabeculae. Sulfated
      glycosaminoglycans, detected by high iron diamine (HID), were distributed in the
      matrix in a pattern similar to that of calcified matrix of the trabeculae.
      Cortical bone was negatively stained by HID. In undecalcified specimens,
      calcified nodules were seen in areas undergoing calcification. Globular
      structures composed of fine filamentous materials, a marginal dense layer, and
      central core, were also observed in the matrix of decalcified specimens. Both the
      calcified nodules and globular structures showed the same distribution pattern,
      i.e., they were dispersed at surface areas and coalesced in the deeper areas of
      the matrix. The globular structures were exclusively positive for HID
      thiocarbohydrazide-silver protein (HID-TCH-SP) stain, indicating the localization
      of sulfated glycosaminoglycans. These results strongly suggest that medullary
      bone calcification progresses by the coalescence of calcified nodules and that
      sulfated glycosaminoglycans play an important role for the regulation of globular
      calcification.

PMID- 11505369
TI  - Caveolar and intercellular channels provide major transport pathways of
      macromolecules across vascular endothelial cells.
AB  - Serum macromolecules are transported through the vascular endothelial layer to
      the interstitium via the caveolae and interendothelial clefts, but the nature of
      the permeability of these structures is unknown, and the manner of caveola
      vesicle transport is controversial. We have developed a method of detecting
      macromolecular channels using an in situ HRP perfusion into arteries previously
      perfused with aldehyde and random conventional sectioning for electron
      microscopy. Using unbiased morphometry, 4.75% of the abluminal caveolae and
      15.13% of the intercellular clefts were the tracer-positive in rat aortic
      endothelium. In rat aortas treated with N-ethylmaleimide, all caveolae and most
      free vesicles in the cytoplasm except those around the Golgi area were HRP
      positive in the endothelial cells; 1.48% of abluminal caveolae were structurally
      recognized as caveolar channels through the endothelial layer in a plane of
      single section. The length density of the abluminal caveolae was decreased to
      about 80% to the physiological control level whereas the larger invaginations
      were more frequently observed. Moreover 96.17% of the intercellular clefts were
      HRP-positive. We suggest that a flexible channel-system functions extensively as
      a macromolecular transport pathway in the arterial endothelium in vivo because
      the tracer-labeled abluminal caveolae and intercellular clefts should be opened
      to the luminal surfaces methodologically. We therefore propose that caveolar
      channels, rather than transcytosis, provide a mechanism of caveola-vesicle
      transport in the endothelial cells, because free vesicles involved in
      transcytosis were few in number.

PMID- 11505370
TI  - Localization of luteinizing-hormone releasing hormone binding sites in the
      gastric mucosa of suckling rats.
AB  - Luteinizing-hormone releasing hormone (LHRH) is a hypothalamic and milk-borne
      hormone that inhibits the cell proliferation of gastric epithelium in developing
      rats, although the mechanism of such action is unknown. We investigated the
      presence of binding sites for LHRH in the stomach of suckling rats after the
      injection of the hormone. Immunofluorescence at the confocal microscopy level
      revealed that LHRH binds to gastric cells, being particularly abundant over the
      gland. Different fluorescent lectins were used to identify gastric cell types and
      determine which were labeled by the hormone. Colocalization studies in these
      double-labeling experiments showed that LHRH staining colocalizes with parietal
      cells, suggesting the presence of binding sites in these cells. The three
      dimensional (3-D) reconstruction of isolated parietal cells revealed the
      localization of the signal, which appears to be in the membrane of the
      canalicular region. These results suggest that there are binding sites for LHRH
      in the gastric epithelium, specifically in parietal cells, and they might play a
      role in the control of cell proliferation during suckling.

PMID- 11505371
TI  - Human reserve pluripotent mesenchymal stem cells are present in the connective
      tissues of skeletal muscle and dermis derived from fetal, adult, and geriatric
      donors.
AB  - This study details the profile of 13 cell surface cluster differentiation markers
      on human reserve stem cells derived from connective tissues. Stem cells were
      isolated from the connective tissues of dermis and skeletal muscle derived from
      fetal, mature, and geriatric humans. An insulin/dexamethasone phenotypic bioassay
      was used to determine the identity of the stem cells from each population. All
      populations contained lineage-committed myogenic, adipogenic, chondrogenic, and
      osteogenic progenitor stem cells as well as lineage-uncommitted pluripotent stem
      cells capable of forming muscle, adipocytes, cartilage, bone, fibroblasts, and
      endothelial cells. Flow cytometric analysis of adult stem cell populations
      revealed positive staining for CD34 and CD90 and negative staining for CD3, CD4,
      CD8, CD11c, CD33, CD36, CD38, CD45, CD117, Glycophorin-A, and HLA DR-II.

PMID- 11505372
TI  - Microvascular architecture of the rat choroid: corrosion cast study.
AB  - This study presents the details of the microvasculature of the rat choroid
      visualized by scanning electron microscopy of vascular corrosion casts. Wistar
      Kyoto rats were anesthetized with intraperitoneal sodium pentobarbital. The
      vascular system was perfused with heparinized saline, and Mercox resin was
      injected into the cannulated carotid arteries. After polymerization of the resin,
      the vascular casts were macerated with potassium hydroxide, washed with water,
      and freeze dried. The casts were examined with a Hitachi S-2360N scanning
      electron microscope (SEM). Corrosion casts of the entire choroidal vasculature
      revealed that the two long posterior ciliary arteries supplied the entire uveal
      vasculature. In the posterior choroid, these arteries formed five to seven
      branches on each side supplying the adjacent choriocapillaris. No interarterial
      or arteriovenous anastomoses were seen. The choriocapillaris appeared as a
      nonhomogeneous and nonlobular monolayer capillary network, consisting of dense
      honeycomb and irregular patterns. There are two distinct venous systems in the
      rat choroid. The venous blood from the central region, peripapillary choroid, and
      sometimes the optic nerve head drain into the posterior ciliary vein. The venous
      blood from the iris, ciliary body, anterior choroid, and half of the posterior
      choroid drain into the vortex veins. Corrosion casts and the SEM have shown
      details of the choroidal vascular architecture. These three-dimensional
      observations indicate that the rat choroidal vasculature has different features
      from those of humans and other primates. Despite these interspecies differences,
      the establishment of a thorough baseline concept of choroidal vasculature should
      permit additional studies of the choroidal pathology and enable the proper
      interpretation of results from rat experimental models for extrapolation to
      humans.

PMID- 11505373
TI  - Osteoblastic differentiation of periosteum-derived cells is promoted by the
      physical contact with the bone matrix in vivo.
AB  - The periosteum contains osteoprogenitors that differentiate to osteoblasts in
      bone growth or repair. Our previous studies suggested the hypothesis that the
      physical contact of the periosteum with the bone matrix is requisite for the
      differentiation of osteoblasts. To test the hypothesis, the present study was
      designed to investigate how the contact between the periosteum and the bone
      matrix influences the osteoblastic differentiation of periosteal cells with
      establishing a new experimental model in vivo. Differentiation of osteoblasts was
      assessed by gene expression of type I collagen, osteocalcin and bone sialoprotein
      using in situ hybridization. A barrier was designed to prevent periosteal cells
      from contacting the bone matrix using the membrane filter. The membrane filter
      was inserted surgically between the surface of rat parietal bone and the
      periosteum after being punched out with pin holes. Periosteal cells were allowed
      to contact with the bone surface only through the pin holes. The pin hole was
      filled with cells derived from the periosteum 1 week after inserting the filter.
      Differentiation of osteoblasts in week 2 and noticeable bone formation in week 3
      were identified on the bone surface only under the pin hole but not under the
      filter. The present study demonstrated that the physical contact with the bone
      matrix promotes osteoblastic differentiation of periosteum-derived cells in vivo.

PMID- 11505374
TI  - Characteristics of the uterine luminal surface epithelium at preovulatory and
      preimplantation stages in the marmoset monkey.
AB  - Light and electron microscopy was used to examine the apical luminal epithelial
      surface of the uterus at preovulatory and preimplantation stages in the marmoset
      monkey. Luminal surface charge, detected by cationic ferritin staining,
      progressively decreased from preovulation to day 11 of pregnancy. The smooth,
      regular apical plasma membrane at preovulatory stages was in contrast to the
      convoluted, irregular surface observed during early pregnancy, especially at 1
      day before blastocyst implantation. Profiles of microvilli were also altered,
      becoming thicker and more irregular during early pregnancy. Within the epithelial
      cell body, cyclic morphologic changes were seen, largely in association with
      secretory organelles. Giant phagocytic bodies were prominent at all stages
      examined, although their composition and intensity of staining varied throughout
      the cycle. Weak to moderate estrogen alpha and progesterone receptor
      immunostaining of the luminal epithelium was found during preovulatory and early
      pregnancy stages. This study describes complex cyclic changes in the morphology
      and biochemical make-up of the uterine luminal epithelial surface in a New World
      monkey in preparation for blastocyst attachment.

PMID- 11505375
TI  - Evidence of a common pathogenesis for foregut duplications and esophageal atresia
      with tracheo-esophageal fistula.
AB  - The pathogenesis of the alimentary tract duplications, including foregut
      duplications (FgD) remains speculative. The accidental finding of FgD in fetal
      rats with esophageal atresia and tracheoesophageal fistula (EA-TEF) induced by
      Adriamycin provided an animal model to investigate a possible relationship
      between these two entities. Timed-pregnant rats were intraperitoneally injected
      with Adriamycin (1.75 mg/kg) on gestational Days 6 to 9. Their embryos were
      harvested by Caesarean section from gestational Days 14 to 21. Forty-six of
      embryos were processed and serially sectioned in the transverse or sagittal
      planes. EA-TEF occurred in 43/46 (93%) embryos of which 11 (24%) were found to
      have an associated FgD located at the level where the esophagus was absent. Six
      FgDs communicated with the foregut or the trachea. Five noncommunicating FgDs
      were located between the foregut and the vertebral column. In the control embryo,
      the notochord was located in the centre of the vertebral column from Day 11 of
      the gestation. In Day 14, 15 and 16, however, embryos exposed to Adriamycin, an
      abnormal notochord or branch frequently was located within the mesenchyme of the
      maldeveloped foregut or attached to the duplication cyst. In some, it appeared
      that the notochord was drawing the cyst-like structure away from the foregut. The
      present study confirms that duplications adjacent to the esophagus arise from the
      foregut and that failure of the foregut to detach from the notochord at the
      normal time may contribute to the development of foregut duplications.

PMID- 11505377
TI  - Clinical, histologic, and electron microscopy study of skin exposed to low
      frequency ultrasound.
AB  - The use of low-frequency ultrasound has been proposed to enhance the transdermal
      transport of various drugs, a technique referred to as sonophoresis. The aim of
      the present study was to determine the safety of low-frequency sonophoresis on
      human and rat skin by evaluating their structural modifications after ultrasound
      exposure. Human skin samples and hairless rats were exposed to 20 kHz ultrasound
      in vitro and in vivo, respectively. Ultrasound was used with average intensities
      ranging from 0.25 to 7 W/cm(2) in pulsed or continuous mode. Hairless rats were
      also exposed to a heat source mimicking the temperature versus time profile
      during sonication. Skin samples were observed under optical and electron
      microscopy to detect any structural changes. Human skin samples exposed to
      intensities lower than 2.5 W/cm(2) showed no modification. For hairless rats,
      slight and transient erythema was observed after 2.5 W/cm(2) exposure, whereas
      deep lesions (dermal and muscle necrosis) were observed 24 hr later. These
      lesions were also observed when a plastic film was placed between the coupling
      medium and the animals' skin during sonication. In contrast, no histologic lesion
      could be seen when a heat source was applied to animal skin. Low-frequency
      ultrasound induces delayed and deep lesions in hairless rat skin at 2.5 W/cm(2)
      which are not only attributable to the increase in temperature at the skin
      surface during ultrasound exposure. By using the same ultrasound conditions,
      human skin seems to be less sensitive in vitro.

PMID- 11505376
TI  - Ultrastructure of the embryonic stem cells of the 8-day pig blastocyst before and
      after in vitro manipulation: development of junctional apparatus and the lethal
      effects of PBS mediated cell-cell dissociation.
AB  - Ultrastructural examination of 8-day hatched pig blastocysts (large and small),
      their cultured inner cell mass (ICM), and cultured epiblast tissue (embryonic
      stem cells) was undertaken to assess the development of epiblast cell junctions
      and cytoskeletal elements. In small blastocysts, epiblast cells had no desmosomes
      or tight junction (TJ) connections and few organized microfilament bundles,
      whereas in large blastocysts the epiblast cells were connected by TJ and
      desmosomes with associated microfilaments. ICM isolation by immunodissection
      damaged the endoderm cells beneath the trophectoderm cells but did not appear to
      damage the epiblast cells or their associated endoderm cells. Epiblast cells in
      cultured ICMs were similar in character to those in the intact large blastocyst
      except that perinuclear microfilaments were observed. Isolated pig epiblasts,
      cultured for approximately 36 hr on STO feeder layers, formed a monolayer whose
      cells were connected by TJ, adherens junctions and desmosomes with prominent
      microfilament bundles running parallel to the apical cytoplasmic membranes.
      Perinuclear microfilaments were a consistent feature in the approximately 36 hr
      cultured epiblast cells. A feature characteristic of differentiation into
      notochordal cells, i.e., a solitary cilium, was also observed in the cultured
      epiblast. Exposure of the cultured epiblast cells to Ca(++)-Mg(++)-free phosphate
      buffered saline (PBS) for 5-10 min resulted in extensive cell blebbing and lysis.
      The results may indicate that pig epiblast cells could be more easily dissociated
      from early blastocysts ( approximately 400 microm in diameter) if
      immunodissection damage to the ICM can be avoided. It may be difficult, however,
      to establish them as embryonic stem cell lines because the cultured pig epiblast
      cells were easily lysed by standard cell-cell dissociation methods.

PMID- 11505378
TI  - On-line size measurement of yeast aggregates using image analysis.
AB  - Alcohol fermentation productivity can be strongly improved using a flocculation
      based yeast recycle. However, the efficiency of the biomass retention system
      depends strongly on the yeast particle size. Accordingly, the monitoring and
      control of yeast floc diameter are of primary importance. The on-line measurement
      of mean floc diameter has been achieved using on-line image analysis, based on
      the evaluation of image texture. The texture analysis method consisted in the
      building of a co-occurrence matrix from which the so-called "Energy parameter"
      was extracted. While image texture is usually used for classification purposes,
      it has been used here as a quantitative descriptor: a correlation has been found
      between this statistical image feature and off-line manual floc-size
      determinations. In the floc-size range investigated (X 0.5-4.3 mm), the evaluated
      mean diameter was in good agreement with the actual particle size, with a
      determination coefficient equal to 0.980. In contrast with manual measurements,
      slow and tedious, this method gave the value of the mean particle diameter in
      real-time, without sampling. This novel tool has been used to investigate the
      behavior of yeast aggregates as a function of fermentation conditions. While
      biomass concentration was kept constant, step increases of the feed rate led to a
      decrease of the mean floc diameter. Image analysis showed that the particle-size
      reduction could occur within a few minutes after modification of the medium
      dilution rate, demonstrating the disruptive effect of the CO(2) efflux. The
      kinetic of aggregate formation was dependent on the gas-phase composition.
      Instead of recycling fermentation gas, sparging the fermentor with nitrogen, to
      reduce dissolved CO(2) concentration, increased the rate of floc-size growth.

PMID- 11505379
TI  - Functional expression and stabilization of horseradish peroxidase by directed
      evolution in Saccharomyces cerevisiae.
AB  - Biotechnology applications of horseradish peroxidase (HRP) would benefit from
      access to tailor-made variants with greater specific activity, lower K(m) for
      peroxide, and higher thermostability. Starting with a mutant that is functionally
      expressed in Saccharomyces cerevisiae, we used random mutagenesis, recombination,
      and screening to identify HRP-C mutants that are more active and stable to
      incubation in hydrogen peroxide at 50 degrees C. A single mutation (N175S) in the
      HRP active site was found to improve thermal stability. Introducing this mutation
      into an HRP variant evolved for higher activity yielded HRP 13A7-N175S, whose
      half-life at 60 degrees C and pH 7.0 is three times that of wild-type
      (recombinant) HRP and a commercially available HRP preparation from Sigma (St.
      Louis, MO). The variant is also more stable in the presence of H(2)O(2), SDS,
      salts (NaCl and urea), and at different pH values. Furthermore, this variant is
      more active towards a variety of small organic substrates frequently used in
      diagnostic applications. Site-directed mutagenesis to replace each of the four
      methionine residues in HRP (M83, M181, M281, M284) with isoleucine revealed no
      mutation that significantly increased the enzyme's stability to hydrogen
      peroxide.

PMID- 11505380
TI  - Metabolic engineering of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) composition
      in recombinant Salmonella enterica serovar typhimurium.
AB  - A recombinant strain of Salmonella enterica serovar Typhimurium (mutant in
      propionate-activation activity) was metabolically engineered to control the
      composition of poly(3-hydroxybutyrate-co-3-hydroxy- valerate) (PHBV), a
      polyhydroxyalkanoate copolymer with commercially desirable properties. A gene
      (prpE) encoding propionyl-CoA synthetase was placed under the control of the IPTG
      inducible taclacUV5 promoter (P(taclacUV5)) while the polyhydroxyalkanoate
      synthesis operon (phaBCA) from Acinetobacter sp. RA3849 was coexpressed under the
      control of the arabinose-inducible araBAD promoter (P(BAD)). S. enterica,
      harboring both constructs, was grown in medium containing a fixed substrate
      concentration and the composition of the copolymer was varied between 2 mol% and
      25 mol% 3-hydroxyvalerate by controlling the IPTG level in the medium. This "dial
      a-composition" system should find application in cases where the substrate
      concentration of a feedstream for PHBV bioplastic production is not adjustable.

PMID- 11505381
TI  - Longterm stability of phase I and phase II enzymes of porcine liver cells in flat
      membrane bioreactors.
AB  - Recently, researchers have focused on the use of bioartificial liver devices to
      support patients with fulminant hepatic failure. Our team developed a cell-based
      flat membrane bioreactor (FMB). In this, porcine liver cells were maintained in
      3D-coculture between two gel layers in a sandwich configuration for 3 weeks to
      study the influence of this bioreactor technique on the preservation of basic,
      not induced activities of phase I and phase II enzymes. First, the time and
      substrate dependencies of the following enzymes were measured: ethoxyresorufin-O
      deethylase (EROD, CYP 1A1/1A2) and ethoxycoumarin-O-deethylase (ECOD, CYP 2B6) as
      phase I enzymes, and glutathione-S-transferase (GST), UDP-glucuronosyltransferase
      (UGT) and sulfotransferase (ST) as phase II enzymes. To find optimal test
      conditions Michaelis-Menten kinetics were calculated. Next, different potential
      inducers were tested to find out the most effective compounds. Based on these
      results, the basic, not induced levels of the different enzymes were determined
      in the flat membrane bioreactor. Furthermore, the response of these enzyme
      activities to the chosen inducers was investigated to examine whether the cells
      keep their ability for drug-drug interactions. Basic, not induced activities of
      both phase I enzymes and the phase II enzymes GST and UGT were maintained at
      nearly the initial levels during the complete period of study. In addition, it
      was possible to induce these enzymes twice or three times in a weekly interval.
      In contrast, the basic, not induced activity of ST increased during the first 10
      days of culture. It stabilized then and was maintained steady. As in short-term
      investigations, no reaction of the ST-activity towards any inducer could be
      obtained. These results prove that porcine liver cells preserve their phase I and
      phase II activities and respond to inducing drugs over 3 weeks in culture.
      Therefore, the flat membrane bioreactor is not only suitable for investigating
      drug metabolism, drug-drug interactions, and enzyme induction but also for
      supporting liver functions.

PMID- 11505382
TI  - Utilizing genetically engineered bacteria to produce plant-specific glucosides.
AB  - Plant-derived glucosides have attracted much attention due to their widespread
      applications. This class of products is difficult to isolate or to synthesize in
      pure form because of the resulting low yields. Thus, simple approaches for the
      generation of such glucosides would be highly beneficial. We purified and
      characterized a novel glucosyltransferase from plant cell suspension cultures of
      Rauvolfia serpentina, which showed rather low substrate specificity. We obtained
      its cDNA and expressed the active recombinant protein in bacteria (Escherichia
      coli) with excellent plant-specific glucosylation efficiencies. Compared with the
      plant system, the bacteria delivered the new enzyme, which was in the form of a
      soluble or matrix-bound enzyme, approximately 1800 times more efficiently for the
      synthesis of a wide range of glucosides. More importantly, the engineered E. coli
      strain allowed for in vivo glucosylation and release of the product into the
      culture medium, as shown by the formation of arbutin, which is a potent inhibitor
      of human melanin biosynthesis with commercial value.

PMID- 11505383
TI  - Stoichiometric growth model for riboflavin-producing Bacillus subtilis.
AB  - Rate equations for measured extracellular rates and macromolecular composition
      data were combined with a stoichiometric model to describe riboflavin production
      with an industrial Bacillus subtilis strain using errors in variables regression
      analysis. On the basis of this combined stoichiometric growth model, we explored
      the topological features of the B. subtilis metabolic reaction network that was
      assembled from a large amount of literature. More specifically, we simulated
      maximum theoretical yields of biomass and riboflavin, including the associated
      flux regimes. Based on the developed model, the importance of experimental data
      on building block requirements for maximum yield and flux calculations were
      investigated. These analyses clearly show that verification of macromolecular
      composition data is important for optimum flux calculations.

PMID- 11505384
TI  - Metabolic flux analysis with a comprehensive isotopomer model in Bacillus
      subtilis.
AB  - Fluxes in central carbon metabolism of a genetically engineered, riboflavin
      producing Bacillus subtilis strain were investigated in glucose-limited chemostat
      cultures at low (0.11 h(-1)) and high (0.44 h(-1)) dilution rates. Using a
      mixture of 10% [U-(13)C] and 90% glucose labeled at natural abundance, (13)C
      labeling experiments were carried out to provide additional information for
      metabolic flux balancing. The resulting labeling pattern in the proteinogenic
      amino acids were analyzed by two-dimensional [(13)C, (1)H] nuclear magnetic
      resonance (NMR) spectroscopy. To account rigorously for all available data from
      these experiments, we developed a comprehensive isotopomer model of B. subtilis
      central metabolism. Using this model, intracellular carbon net and exchange
      fluxes were estimated on the basis of validated physiological data and biomass
      composition in combination with 2D NMR data from 45 individual carbon atom
      spectra in the amino acids. Glucose catabolism proceeded primarily via glycolysis
      but pentose phosphate pathway fluxes increased with increasing growth rate.
      Moreover, significant back fluxes from the TCA cycle to the lower part of
      glycolysis via the gluconeogenic PEP carboxykinase were detected. The malic
      enzyme reaction, in contrast, was found to be inactive. A thorough statistical
      analysis was performed to prove the reliability of the isotopomer balance model
      and the obtained results. Specifically, a chi(2) test was applied to validate the
      model and the chi-square criterion was used to explore the sensitivity of model
      predictions to the experimental data.

PMID- 11505385
TI  - A lipid-coated lipase as an efficient hydrolytic catalyst in the two-phase
      aqueous-organic system.
AB  - A lipid-coated lipase has been known to be soluble in organic solvents and act as
      an efficient esterification catalyst in the dry organic solvent. It was also
      found to act as an efficient hydrolytic catalyst for lipophilic esters in the two
      phase aqueous-organic system. Both the lipid-coated lipase and substrates are
      solubilized in the organic phase and the hydrolysis occurs with water molecules
      from the aqueous phase. Therefore, the reaction was 40-100 times faster than that
      of the native lipase, in which the enzyme and substrate exist separately in the
      aqueous and organic phase, respectively, and the reaction proceeded at the
      interface. The hydrolysis rates for the lipid-coated lipase were not affected by
      the aqueous pH and agitation speed of the two-phase. Enzymatic activity of the
      lipid-coated lipase was compared with that of the poly(ethylene glycol)-grafted
      lipase. Michaelis-Menten kinetics in the two-phase reactions was also studied.

PMID- 11505386
TI  - Production of tissue plasminogen activator (t-PA) in Aspergillus niger.
AB  - A protease-deficient strain of Aspergillus niger has been used as a host for the
      production of human tissue plasminogen activator (t-PA). In defined medium, up to
      0.07 mg t-PA (g biomass)(-1) was produced in batch and fed-batch cultures and
      production was increased two- to threefold in two-phase batch cultures in which
      additional glucose was provided as a single pulse at the end of the first batch
      growth phase. Production was increased [up to 1.9 mg t-PA (g biomass)(-1)] by the
      addition of soy peptone to the defined medium. The rate of t-PA production in
      batch cultures supplemented with soy peptone (0.2 to 0.6 mg t-PA L(-1) h(-1)) was
      comparable to rates observed previously in high-producing mammalian or insect
      cell cultures. In glucose-limited chemostat culture supplemented with soy
      peptone, t-PA was produced at a rate of 0.7 mg t-PA L(-1) h(-1). Expression of t
      PA in A. niger resulted in increased expression of genes (bipA, pdiA, and cypB)
      involved in the unfolded protein response (UPR). However, when cypB was
      overexpressed in a t-PA-producing strain, t-PA production was not increased. The
      t-PA produced in A. niger was cleaved into two chains of similar molecular weight
      to two-chain human melanoma t-PA. The two chains appeared to be stable for at
      least 16 h in culture supernatant of the host strain. However, in general, <1% of
      the t-PA produced in A. niger was active, and active t-PA disappeared from the
      culture supernatant during the stationary phase of batch cultures, suggesting
      that the two-chain t-PA may have been incorrectly processed or that initial
      proteolytic cleavage occurred within the proteolytic domain of the protein. Total
      t-PA (detected by enzyme-linked immunoassay) also eventually disappeared from
      culture supernatants, confirming significant extracellular proteolytic activity,
      even though the host strain was protease-deficient.

PMID- 11505387
TI  - Development of expression systems for the production of recombinant human serum
      albumin using the MOX promoter in Hansenula polymorpha DL-1.
AB  - To optimize the secretory expression of recombinant human serum albumin (HSA)
      under the control of methanol oxidase (MOX) promoter in the methylotrophic yeast
      Hansenula polymorpha DL-1, we analyzed several parameters affecting the
      expression of HSA from the MOX promoter. Removal of the 5'-untranslated region
      derived from HSA cDNA in the expression cassette led to at least a fivefold
      improvement of HSA expression efficiency at the translational level. With the
      optimized expression cassette, the gene dosage effect on HSA expression was
      abolished and thus, a single copy of the expression vector integrated into the
      MOX locus became sufficient for the maximal expression of HSA. Northern blot
      analysis revealed that the levels of HSA transcript did not increase any further
      upon increasing copy number. The mox-disrupted (mox Delta) transformant was
      constructed, in which the genomic MOX gene was transplaced with the HSA
      expression cassette, to examine the effect of the methanol oxidase-deficient
      phenotype of the host on HSA expression. The mox Delta transformant showed higher
      levels of HSA production in shake-flask cultures than the MOX wild-type
      transformant, especially at low concentrations of methanol and a twofold higher
      specific HSA production rate in fed-batch fermentation with an abrupt induction
      mode. The native prepro signal sequence of HSA secreted in H. polymorpha was
      correctly processed and the mature recombinant protein had a pI value identical
      to that of the authentic HSA. Our results suggest that the H. polymorpha
      expression systems developed in this study are suitable for large-scale
      production of recombinant albumin.

PMID- 11505388
TI  - Advanced Hodgkin disease with large mediastinal involvement can be treated with
      eight cycles of chemotherapy alone after a major response to six cycles of
      chemotherapy: a study of 82 patients from the Groupes d'Etudes des Lymphomes de
      l'Adulte H89 trial.
AB  - BACKGROUND: The prognostic impact of large mediastinal involvement
      (mediastinum/thorax [M/T] ratio > 0.33) in advanced Hodgkin disease (HD) and the
      optimal treatment with chemotherapy or combined treatment remains controversial.
      METHODS: Among 533 assessable patients with Ann Arbor Stage IIIB/IV HD included
      in the H89 trial, 82 had large mediastinal mass defined on chest X-ray. All
      patients received induction with six cycles of chemotherapy (mechlorethamine,
      vincristine, procarbazine, prednisone-doxorubicin, bleomycin, vinblastine or
      doxorubicin, vinblastine, bleomycin, procarbazine, prednisone); then complete and
      good partial responders were randomized between two consolidation treatments: 2
      cycles of the same chemotherapy or (sub)total lymph node irradiation. RESULTS:
      Among 82 patients with an M/T ratio greater than 0.33, 48 were very large (ratio
      > 0.45). A large mediastinal mass was associated with supradiaphragmatic disease,
      younger age, histologic nodular sclerosis, and different sex ratio compared with
      other H89 trial patients. Biologic parameters and prognostic factors were similar
      for both groups. Although the major response rate to induction chemotherapy
      (after 6 cycles) was lower for patients with large mediastinal mass (78% vs.
      86%), the 5-year overall survival rate (80% vs. 79%) and event free survival rate
      (59% vs. 61%) were similar (P = 0.64 and 0.3, respectively). The outcome was the
      same for patients (74%) with a large mediastinal mass randomized to 1 of the 2
      consolidation arms. Analysis of progression showed that 68% (21 of 31) of
      failures occurred early during treatment and involved the mediastinum in 86% of
      the cases. CONCLUSIONS: For patients with large mediastinal mass and advanced HD
      who achieved a major response of at least 75% after 6 cycles of chemotherapy, a
      consolidation radiation therapy can be replaced by 2 additional cycles of
      chemotherapy.

PMID- 11505389
TI  - Receptor activator of nuclear factor-kappaB ligand and osteoprotegerin: potential
      implications for the pathogenesis and treatment of malignant bone diseases.
AB  - BACKGROUND: The current review summarizes the roles of the ligand, receptor
      activator of nuclear factor-kappaB ligand (RANKL), its receptor, receptor
      activator of nuclear factor-kappaB (RANK), and its decoy receptor,
      osteoprotegerin (OPG), on osteoclast biology and bone resorption. Furthermore, it
      highlights the impact of these compounds on the pathogenesis of malignant bone
      diseases, including tumor metastasis, humoral hypercalcemia of malignancy, and
      multiple myeloma. Finally, the authors discuss the therapeutic potential of OPG
      in the management of malignancies involving the skeleton. METHODS: After its
      discovery and cloning, the biologic effects of RANKL, RANK, and OPG have been
      characterized by in vitro experiments and in vivo studies. The generation of
      knock-out mice and transgenic mice has produced animal models with absent or
      excessive production of these cytokine components that display opposite abnormal
      skeletal phenotypes (osteoporosis or osteopetrosis). The potential effect of
      RANKL and OPG has been assessed by evaluating these compounds in various animal
      models of metabolic and malignant bone disease and by administering OPG to
      humans. RESULTS: Abnormal bone resorption due to local or systemic stimulation of
      osteoclast differentiation and activation is a hallmark of various benign and
      malignant bone diseases. RANKL, RANK, and OPG form an essential cytokine system
      that is capable of regulating all aspects of osteoclast functions, including
      proliferation, differentiation, fusion, activation, and apoptosis. The balance of
      bone resorption depends on the local RANKL-to-OPG ratio, which is enhanced in
      bone metastases and humoral hypercalcemia of malignancy. The exogenous
      administration of OPG to tumor-bearing animals corrects the increased RANKL-to
      OPG ratio, and reverses the skeletal complications of malignancies. CONCLUSIONS:
      Abnormalities of the RANKL/OPG system have been implicated in the pathogenesis of
      various primary and secondary bone malignancies. The systemic administration of
      OPG appears to be a potent novel therapeutic agent for treatment of these
      disorders.

PMID- 11505390
TI  - Improved accuracy in differentiating malignant from benign mammographic
      abnormalities: a simple, improved magnetic resonance imaging method.
AB  - BACKGROUND: Although several refinements have been reported for breast magnetic
      resonance imaging (MRI), there has been no uniform agreement by researchers on
      the optimal method. The authors report a simple and effective MRI method that
      incorporated the best qualities of other breast MRI methods yet eliminated the
      complexity of dynamic sequences and computer subtraction. This new method used
      fat-suppression, a 3D technique, a dedicated breast coil, and quantitation of
      lesion enhancement. METHODS: Sixty-one mammographically suspicious lesions were
      evaluated with a fat-suppressed T1-weighted 3D FLASH sequence before and after
      administration of Gd-DTPA. Abnormalities were evaluated primarily by the degree
      of lesional enhancement; lesional morphology was assessed as a secondary
      criterion. For small or multiple lesions, the authors reformatted images to
      produce MRI findings that corresponded to the mammographic abnormality. To allow
      accurate pathologic correlation, all subjects underwent stereotactic or
      excisional biopsy of the suspicious lesions. RESULTS: Using this new method, all
      15 breast carcinomas were enhanced with a signal intensity (SI) increase of > or
      = 180% (mean = 337%). No benign lesions enhanced at a SI of > 180%. The
      difference in degree of enhancement between malignant and benign lesions was
      statistically significant (P < 0.05). There were overlapping degrees of
      postcontrast enhancement among fibroadenomas (n = 13; mean SI = 70%) and atypical
      hyperplasias (n =; 11; mean SI = 82%), but morphologic characteristics allowed
      for discrimination between these two entities. In the remaining benign breast
      disease lesions, there was minimal enhancement. CONCLUSIONS: 3D fat-suppressed
      sequencing using this new MRI method accurately discriminated between benign and
      malignant mammographic abnormalities and eliminated the time-intensive and
      complex MRI methods without sacrificing accuracy.

PMID- 11505391
TI  - Increased frequency of ATM mutations in breast carcinoma patients with early
      onset disease and positive family history.
AB  - BACKGROUND: An increased incidence of breast carcinoma has been reported among
      relatives of individuals who are affected with the rare recessive disorder,
      ataxia-telangiectasia (A-T), and who are heterozygous for mutations in the ataxia
      telangiectasia mutated (ATM) gene. However, most studies of breast carcinoma
      cases from the general population have failed to find a higher incidence of ATM
      mutations in cases when compared with controls. METHODS: Genomic DNA samples from
      258 individuals were screened for mutations of all types in each of the 62 coding
      exons of the ATM gene; 142 of these were from breast carcinoma cases with a first
      degree family history or early age at diagnosis, 35 were from cases selected for
      the presence of either known disease-related mutations (n = 25) or missense
      alterations of unknown consequences (n = 10) in BRCA1 or BRCA2, and 81 were from
      matched controls. RESULTS: A total of 12 individuals with ATM mutations were
      identified, 11 among 142 breast carcinoma cases (7.7%; 95% CI, 3.9-13.4%) and 1
      among 81 controls (1.2%; 95% CI, 0.0-6.7%) (P = 0.06). All mutations detected
      were of the missense type; none were predicted to truncate the ATM protein. Among
      cases, mutations were found exclusively in patients with a family history of
      breast carcinoma (12.1%; 95% CI, 6.2-20.6%) (P = 0.02). Similar frequencies of
      ATM mutations were found in 35 additional cases selected for the presence of
      BRCA1 or BRCA2 mutations when compared with cases overall. CONCLUSIONS: ATM
      mutations, specifically missense mutations, are more common in breast carcinoma
      cases selected for first-degree family history and early age at diagnosis.

PMID- 11505392
TI  - The association of K-ras gene mutation and vascular endothelial growth factor
      gene expression in pancreatic carcinoma.
AB  - BACKGROUND: Previously, the authors reported the role of the vascular endothelial
      growth factor (VEGF) as an angiogenic factor in 40 patients with pancreatic
      carcinoma. In this study, they investigated the mechanism underlying the
      regulation of VEGF gene expression and evaluated VEGF expression and K-ras gene
      status in 48 patients with pancreatic carcinoma. METHODS: The authors used
      quantitative reverse transcriptase-polymerase chain reaction analysis and direct
      sequencing techniques for a retrospective study of VEGF gene expression and K-ras
      gene status in tumor tissue samples from 48 patients with pancreatic carcinoma.
      Immunohistochemistry also was used to investigate VEGF protein expression.
      RESULTS: Thirty-one tumors (64.6%) were evaluated with high VEGF expression, and
      17 tumors (35.4%) were evaluated with low VEGF expression. Of the 48 primary
      pancreatic tumors studied, 33 tumors (68.8%) contained mutations of the K-ras
      gene. There was a significant correlation between VEGF expression and K-ras
      status. Twenty-five of 33 tumors (75.8%) with mutant K-ras genes showed high VEGF
      expression, whereas only 6 of 15 tumors with the wild type K-ras (40.0%) showed
      high VEGF expression (P = 0.038). The mean (+/- standard error) VEGF conservation
      rate for the 33 tumors with mutant K-ras was 1.839 +/- 1.241, and that for the 15
      tumors with wild type K-ras was 1.057 +/- 0.983 (P = 0.037). Furthermore, the
      median survival for patients with mutant K-ras was shorter than for those with
      wild type K-ras (10.6 months vs. 27.6 months, respectively; P = 0.026), whereas
      the median survival for patients with high VEGF expression was shorter compared
      with that for patients with low VEGF expression (9.5 months vs. 26.4 months,
      respectively; P = 0.002). Cox regression model analysis indicated that only the
      VEGF status was a significant factor for prognosis (P = 0.024). Other variables,
      i.e., K-ras status, histopathologic tumor grade, tumor status, lymph node status,
      metastatic status, gender, and age at surgery, were not significant. CONCLUSIONS:
      The results of this study suggest that K-ras oncogene mutation may be associated
      with VEGF expression and that patients with pancreatic carcinoma who have high
      VEGF expression are associated with a poor prognosis.

PMID- 11505393
TI  - 2-Methoxyestradiol-induced caspase-3 activation and apoptosis occurs through
      G(2)/M arrest dependent and independent pathways in gastric carcinoma cells.
AB  - BACKGROUND: 2-Methoxyestradiol (2-Me), one of the estrogen metabolites, has
      recently been found to possess anti-angiogenesis activity in vivo. Many
      chemotherapeutic agents, such as taxol, docetaxel, and vinblastine, interact with
      microtubules and then induce apoptosis. It has been suggested that 2-Me acts on
      microtubules and results in G(2)/M-cycle arrest of tumor cells. Whether 2-Me
      induces apoptosis in gastric carcinoma cell lines is not known. Moreover,
      reactive oxygen species (ROS) produced by 2-Me may be involved in cytotoxicity of
      tumor cells. Thus, another objective of this study was to evaluate the relation
      between cell cycle arrest, ROS formation, and caspase activity levels after 2-Me
      treatment in gastric carcinoma cells. METHODS: It was determined whether 2-Me
      directly induced apoptosis in two gastric carcinoma cell lines (SC-M1 and NUGC-3)
      through caspase-3 and caspase-8 activation and, eventually, induced DNA
      fragmentation. To clarify the effect of 2-Me-induced G(2)/M arrest in apoptosis,
      calcium ionophore, A23187, and thapsigargin were used to modulate 2-Me-induced
      cell cycle responses. Moreover, the role of 2-Me-induced ROS formation in the
      cell cycle responses also was evaluated. RESULTS: It was found that 2-Me
      treatment resulted in G(2)/M-cycle arrest, caspase-8 and caspase-3 activation,
      and DNA fragmentation. In addition, the 2-Me induced, concomitant increases of
      peroxide and superoxide anions were correlated with G(2)/M-cycle arrest.
      Treatment with calcium ionophore A23187 and thapsigargin partially reversed the 2
      Me-induced G(2)/M-cycle arrest, with a concomitant decrease in both peroxide and
      superoxide levels. Moreover, A23187 blocked the 2-Me-induced caspase-3
      activation, whereas thapsigargin had no effect. Treatment with calcium channel
      blockers did not affect 2-Me-induced cell cycle arrest or caspase-3 activation.
      CONCLUSIONS: These results suggest that the 2-Me-induced apoptosis of gastric
      carcinoma cells by DNA fragmentation accompanied caspase activation. Elevation of
      free radicals was associated with G(2)/M-cycle arrest. The induction of G(2)/M
      cycle arrest is not a prerequisite for caspase activation.

PMID- 11505394
TI  - Prognostic significance of thymidylate synthase activity in bladder carcinoma.
AB  - BACKGROUND: 5-fluorouracil (5-FU) is an anticancer agent clinically used against
      various cancers including bladder carcinoma. 5-FU inhibits thymidylate synthase
      (TS) and blocks DNA synthesis. TS is the key enzyme in the catalysis of the
      methylation from deoxyuridine monophosphate (dUMP) to deoxythymidine
      monophosphate. Little is known about the significance of TS in bladder carcinoma.
      The authors investigated the activity of TS in 82 bladder cancers and prognostic
      significance of the levels of TS and/or activities of dihydropyrimidine
      dehydrogenase (DPD), an important enzyme in the degradation of 5-FU. METHODS: The
      levels of TS and DPD activities in nonfixed, fresh, frozen, bladder carcinoma and
      normal bladder specimens were determined biochemically by the FdUMP binding assay
      and the 5-FU degradation assay, respectively. RESULTS: The activity of TS was 10
      fold higher in bladder carcinoma compared with normal bladder. TS activity in
      muscle-invasive bladder carcinoma was threefold higher than that in Ta and T1
      cancer. In addition, the activity of TS in T1 bladder carcinoma was threefold
      higher than that in Ta cancer. The level of TS activity in Grade 3 bladder
      carcinoma was 4.5-fold and 3.5-fold higher than that in Grade 1 and Grade 2
      cancers, respectively. Patients with Ta and T1 bladder carcinoma with low TS
      activity had a longer postoperative tumor-free period than those with high
      activity in the 2-year follow-up. Patients with Ta and T1 bladder carcinoma with
      high or low TS activity were divided into four subgroups: high or low DPD
      activity subgroups. Patients with low TS activity and high DPD activity had the
      longest postoperative disease-free period among the 4 subgroups during the 2-year
      follow-up. CONCLUSIONS: To the authors' knowledge, the current study is the first
      study that demonstrated that the level of TS activity correlates with both the
      progression of the stage and the increase of the grade of bladder carcinoma and
      that elevated TS activity predicts early recurrence in Ta and T1 bladder
      carcinoma. These results suggested that elevated TS activity might have been
      associated with a higher chance of progression and recurrence of bladder
      carcinoma in the patients who participated in this study.

PMID- 11505395
TI  - Phase II evaluation of paclitaxel, alpha-interferon, and cis-retinoic acid in
      advanced renal cell carcinoma.
AB  - BACKGROUND: Interferon and 13-cis-retinoic acid (13-CRA) therapy showed clinical
      response rates of 30% in advanced renal cell carcinoma (RCC). This combination
      also enhanced sensitivity to paclitaxel in a bcl-2 and mutant p53 expressing
      renal carcinoma cell line. Based on this, the authors conducted a Phase II
      clinical trial of the combination of interferon, 13-CRA, and weekly paclitaxel,
      in advanced RCC. METHODS: The eligibility criteria consisted of unresectable or
      metastatic RCC, measurable disease, a Southwest Oncology Group performance status
      of 0-2, and adequate bone marrow, hepatic, and renal function. Prior cytotoxic or
      immunologic treatment including interferon was permitted. Paclitaxel was
      administered at a dose of 80 mg/m(2) as a 1-hour intravenous infusion on Days 1,
      8, and 15 of each 28-day cycle. Interferon was administered at a dose of 3
      million units subcutaneously daily and 13-CRA at 1 mg/kg/day orally in 2 divided
      doses for the first 21 days of each cycle. RESULTS: Twenty-one patients were
      enrolled with a median age of 52 years, 16 males and 5 females, 10 patients with
      no prior therapy, 5 each with prior interleukin-2 or interferon therapy, and 1
      patient with both. Four patients had also received prior investigational
      chemotherapy. A total of 61 cycles were administered with a median of 2 per
      patient. Grade 3 and 4 toxicities were neutropenia in three patients, anemia in
      four patients, and asthenia, skin rash, and hypersensitivity reaction in one case
      each. Of the 20 evaluable patients, one objective partial response was observed
      for a duration of 7+ months. Seven patients had disease stabilization. The median
      survival of the entire population was 9.5 months (range, 4-18+ months).
      CONCLUSIONS: The combination of 13-CRA, interferon, and weekly paclitaxel was
      well tolerated and had minimal efficacy in advanced RCC.

PMID- 11505396
TI  - The predictive value for prostate cancer of lesions that raise suspicion of
      concomitant carcinoma: an evaluation from a randomized, population-based study of
      screening for prostate cancer.
AB  - BACKGROUND: Suspicion of prostate carcinoma may persist after an initial negative
      biopsy result, and repeated biopsy is suggested. The authors assessed whether
      diagnostic follow-up of men with an initial diagnosis of isolated, high-grade
      prostatic intraepithelial neoplasia (HPIN) and a prostate biopsy suspicious for
      malignancy (PBSM) is needed. METHODS: The frequency of isolated HPIN and PBSM was
      determined in 4057 participants of a population-based screening study who
      underwent systematic sextant transrectal biopsy. The predictive value for
      prostate carcinoma of HPIN and PBSM was determined by performing repeated
      biopsies at 6-week interval. The additional predictive value for malignant
      disease within a screened population was assessed by performing repeated biopsies
      at a 1-year interval in 462 consecutively recruited men with an initial benign
      biopsy result. Participants were subjected to a second screening at a 4-year
      interval. The biopsy and radical prostatectomy tumor features were determined.
      RESULTS: Isolated HPIN and PBSM were diagnosed in 0.8% and 2.6% of biopsied men,
      respectively. The detection rates on repeated biopsy were 10.0% (3 of 30 men) for
      isolated HPIN, 38.7% (36 of 93 men) for PBSM, and 11.0% (51 of 462 men) for those
      with initial benign biopsy results. Except for two men (one with PBSM and one
      with HPIN), all others remained free of prostate carcinoma at their second
      screening. Features of the tumors that were detected after PBSM were comparable
      to those that were detected on initial biopsy, whereas the few tumors that were
      diagnosed after HPIN had highly favorable features. CONCLUSIONS: Compared with
      men who have PBSM, men with isolated HPIN on initial biopsy are at no greater
      risk of being diagnosed with prostate carcinoma than if their initial biopsies
      were assessed as benign only. Moreover, the features of tumors that are diagnosed
      after an evaluation of HPIN warrant no early, extensive diagnostic follow-up.

PMID- 11505397
TI  - Carbon dye histologically confirms the identity of sentinel lymph nodes in
      cutaneous melanoma.
AB  - BACKGROUND: False-negative results from lymphatic mapping and sentinel
      lymphadenectomy (LM/SL) are associated with technical failures in nuclear
      medicine and surgery or with erroneous histologic evaluation. Any method that can
      confirm sentinel lymph node (SN) identity might decrease the false-negative rate.
      Carbon dye has been used as an adjunct to assist lymphadenectomy for some tumors,
      and the authors hypothesized that it could be used for the histologic
      verification of SNs removed during LM/SL. The current study assessed the clinical
      utility of carbon dye as a histopathologic adjunct for the identification of SNs
      in patients with melanoma and correlated the presence of carbon particles with
      the histopathologic status of the SNs. METHODS: LM/SL was performed using carbon
      dye (India ink) combined with isosulfan blue dye and sulfur colloid. Blue-stained
      and/or radioactive lymph nodes (two times background) were defined as SNs. Lymph
      nodes were evaluated for the presence of carbon particles and melanoma cells. If
      an SN lacked carbon dye in the initial histologic sections, four additional
      levels were obtained with S-100 protein and HMB-45 immunohistochemistry.
      Completion lymph node dissection (CLND) was performed if any SN contained
      melanoma cells. RESULTS: One hundred patients underwent successful LM/SL in 120
      lymph node regions. Carbon particles were identified in 199 SNs from 111 lymph
      node regions of 96 patients. Sixteen patients had tumor-positive SNs, all of
      which contained carbon particles. The anatomic location of the carbon particles
      within these tumor-positive SNs was found to be correlated with the location of
      tumor cells in the SNs. The presence of carbon particles appeared to be
      correlated with blue-black staining (P = 0.0001) and with tumor foci (P = 0.028).
      All 35 non-SNs that were removed during LM/SL were tumor-negative, and only 2
      contained carbon particles. Of the 272 non-SNs removed during CLND, 5 contained
      metastases; 3 of these 5 were the only non-SNs that had carbon particles. The use
      of carbon particles during LM/SL was found to be safe and nontoxic. CONCLUSIONS:
      Carbon dye used in LM/SL for melanoma permits the histologic confirmation of SNs.
      Carbon particles facilitate histologic evaluation by directing the pathologist to
      the SNs most likely to contain tumor. The location of carbon particles within SNs
      may assist the pathologist in the detection of metastases, thereby decreasing the
      histopathologic false-negative rate of LM/SL and subsequently reducing the same
      basin recurrence rate.

PMID- 11505398
TI  - Loss of motility-related protein 1 (MRP1/CD9) and integrin alpha3 expression in
      endometrial cancers.
AB  - BACKGROUND: MRP1/CD9 and integrin alpha3 have played crucial roles in cell
      adhesion, motility, and signaling events. The loss of MRP1/CD9 and integrin
      alpha3 has been involved in tumor growth and metastasis of cancer cells. The aim
      of the current study was to clarify the clinical significance of MRP1/CD9 and
      integrin alpha3 in endometrial cancer. METHODS: The expression of MRP1/CD9 and
      integrin alpha3 from the same tissue sample were examined immunohistochemically
      in 15 patients with normal endometrium and in 56 patients with uterine
      endometrioid adenocarcinoma. Disease-free survival curves were estimated using
      the Kaplan-Meier method and analyzed by the log-rank test between the positive
      and reduced expression statuses of both MRP1/CD9 and integrin alpha3. These
      expressions and clinicopathologic variables were analyzed univariately and
      multivariately. RESULTS: In normal endometrium, MRP/CD9 was expressed at the cell
      membrane of cell contact sites, and the expression of integrin alpha3 was
      detected also at the cell membrane of cell contact sites and at borders of
      stromal tissues. In patients with endometrioid adenocarcinoma, 17 cases showed
      reduced expression of MRP1/CD9, and 20 cases had reduced expression of integrin
      alpha3. Fourteen cases indicated a reduced expression of both MRP1/CD9 and
      integrin alpha3. Each reduced expression of MRP1/CD9 or integrin alpha3 was
      significantly correlated with histologic grade and metastasis. Multivariate
      analysis using the Cox regression model disclosed that age at surgery,
      metastasis, and expression status of MRP1/CD9 were significant prognostic factors
      for disease-free survival. CONCLUSIONS: These findings suggested that the
      analysis for the expression statuses of MRP1/CD9 and integrin alpha3 may provide
      important information on the clinical behavior of endometrial cancer.

PMID- 11505399
TI  - Demographic variations in the rising incidence of esophageal adenocarcinoma in
      white males.
AB  - BACKGROUND: The rise in adenocarcinoma (AC) of the esophagus has been reported in
      several papers. However, the results are only comparable to a limited extent,
      because they are based on differing periods and different computational methods.
      The purpose of the current investigation was to collect the available data and to
      analyze them in a unified manner. METHODS: The authors requested data on the
      incidence of AC of the esophagus for each year since 1960 from 43 tumor
      registries in North America, Europe, and Australia. The data from 22 centers were
      used. The trend was calculated by fitting the data to an exponential growth
      model. RESULTS: The incidence of AC of the esophagus in white males is rising in
      most countries. The highest values of the estimated incidence rate in the year
      2000 were found in Great Britain (5.0- 8.7 cases per 100,000 population) and in
      Australia (4.8 cases per 100,000 population) followed by The Netherlands (4.4
      cases per 100,000 population), the United States (3.7 cases per 100,000
      population), and Denmark (2.8 cases per 100,000 population). Low rates (< 1.0
      cases per 100,000 population) were found in Eastern Europe. The largest changes
      in incidence were reported in the Southern European countries, with an estimate
      of the average increase over six registries of 30% per year; in Australia, with
      an average increase of 23.5% per year; and in the United States, with an average
      increase of 20.6% per year. The rates of increase ranged from 8.7% to 17.5% on
      average in Northern Europe, Central Europe, and the United Kingdom. In Eastern
      Europe, at most, there was a minor rise in incidence. CONCLUSIONS: In the Western
      industrialized nations, the analyzed data show that the incidence of AC of the
      esophagus has been rising rapidly in the last 20 years. The only exceptions to
      date are the countries of Eastern Europe.

PMID- 11505400
TI  - Expression of vascular endothelial growth factor family members in head and neck
      squamous cell carcinoma correlates with lymph node metastasis.
AB  - BACKGROUND: The expression of vascular endothelial growth factor (VEGF)-A
      isoforms (121, 165, 189, 206), VEGF-B, VEGF-C and VEGF-D in both experimental and
      clinical models of head and neck squamous cell carcinoma (HNSCC) was determined
      and correlated with conventional clinicopathologic parameters, with particular
      reference to cervical nodal metastasis. METHODS: The mRNA expression of VEGFs in
      14 HNSCC cell lines was compared with 4 normal keratinocyte cultures and 10
      fibroblast cultures using a semiquantitative reverse transcription polymerase
      chain reaction (RT-PCR) assay. Protein levels were determined by Western blotting
      and enzyme-linked immunosorbent assay (ELISA). The authors then examined the
      expression of VEGFs in tissues from 54 patients including histologically normal
      epithelium (n = 32), early invasive squamous cell carcinomas (SCCs) (n = 23),
      advanced primary SCCs (n = 31), and lymph node metastases (n = 27). RESULTS:
      Increased levels of VEGF-A (all four isoforms) and VEGF-C were found in tumor
      cell lines compared with normal cells, whereas no differences in VEGF-B levels
      were found. VEGF-D expression, however, was lower in HNSCC cells. Studies in
      clinical samples showed highly significant increases in mRNA expression of all
      four isoforms of VEGF-A and VEGF-C in tumors versus normal epithelium. In
      contrast, the levels of VEGF-D were significantly decreased in tumors, and VEGF-B
      expression appeared similar in both normal and malignant tissues. Multivariate
      analysis demonstrated that an infiltrative mode of invasion and enhanced
      expression of VEGF-A (isoforms 121 and 165) and VEGF-C had predictive value for
      the presence of cervical nodal metastases. CONCLUSIONS: Up-regulation of VEGF-A
      (two isoforms) and VEGF-C and down-regulation of VEGF-D have been common features
      in HNSCC. Thus VEGF-A and VEGF-C appeared to play a vital role in the metastatic
      process of HNSCC.

PMID- 11505401
TI  - Phase II study of gemcitabine and cisplatin in the treatment of patients with
      advanced pancreatic carcinoma.
AB  - BACKGROUND: Pancreatic carcinoma is considered among the most chemoresistant of
      human malignancies. The most commonly used cytotoxic single agents, 5
      fluorouracil and 2'-deoxy-2',2'-difluorocytidine (gemcitabine), have objective
      response rates of less than 10% in large studies. Hypothesizing noncross
      resistance and a synergistic interaction between gemcitabine and cisplatin, early
      clinical studies have demonstrated significant activity with this combination in
      patients with several types of malignant disease. A Phase II study was undertaken
      to determine the efficacy of gemcitabine in combination with cisplatin in
      patients with locally advanced and metastatic pancreatic carcinoma based on these
      considerations. METHODS: The eligibility criteria included histologically
      confirmed, locally advanced, unresectable or metastatic exocrine carcinoma of the
      pancreas with no prior gemcitabine therapy; prior adjuvant therapy was allowed
      provided the last day of therapy was at least 6 months prior to starting
      treatment; clinically measurable or evaluable disease; a Southwest Oncology Group
      scale performance status of 0-2; a life expectancy of > 12 weeks; and adequate
      bone marrow, hepatic, and renal function. A total of 42 patients, 4 patients with
      locally advanced, unresectable disease and 38 patients with metastatic disease,
      were treated and received a total of 211 cycles of therapy between May 1997 to
      March 1999. The median age of patients was 61.5 years. The patients were treated
      in the outpatient setting with a combination of gemcitabine 1,000 mg/M(2)
      intravenously over 30 minutes administered on Days 1, 8, and 15 of each cycle and
      cisplatin 50 mg/M(2) intravenously administered after gemcitabine infusion on
      Days 1 and 15 with adequate prehydration accompanied by adequate urinary output.
      Cycles were repeated every 28 days. Response and toxicity were assessed according
      to World Health Organization and standard criteria. RESULTS: The complete and
      partial response rate among all 42 registered patients was 11 of 42 patients
      (26%; 95% confidence interval, 0.14-0.42). Stabilization of disease was seen in
      15 patients (38%). Two additional patients with metastatic disease who achieved
      major responses to chemotherapy were rendered free of disease surgically,
      achieving a complete response status. The median overall survival was 7.1 months
      (95% confidence interval [CI], 6.3-9.1 months), with 64% of patients alive at 6
      months and 19% of patients alive at 12 months. The median time to disease
      progression was 5.4 months (range, 0.9-20.8 months). Major toxicities were
      neutropenia and thrombocytopenia, with one episode of neutropenic fever.
      CONCLUSIONS: The combination of gemcitabine and cisplatin appeared to have
      significantly greater activity than single-agent gemcitabine in this Phase II
      study, with tolerable toxicity. The antitumor activity of this combination needs
      to be confirmed in multi-institutional or comparative trials.

PMID- 11505402
TI  - Multimodality treatment of patients with liver metastases from germ cell tumors:
      the role of surgery.
AB  - BACKGROUND: The presence of liver metastases represents an independent poor risk
      prognostic factor for survival in patients with germ cell tumors. METHODS: The
      clinical files of 37 patients who had undergone liver resection for the treatment
      of disseminated germ cell tumors were reviewed to define the indications for
      resection of residual liver metastases after chemotherapy in patients with germ
      cell tumors. The histologic patterns of primary tumor and residual disease were
      compared. The prognostic factors for survival were studied by univariate
      analysis. RESULTS: All but 2 of 37 patients underwent complete resection. One
      patient died of postoperative complications. Thirteen complications occurred in
      10 patients. Twelve patients had active residual tumor, 7 patients had mature
      teratoma, and 18 patients had only necrosis on histologic examination. Twenty
      three of 37 patients (62%) were alive with no evidence of disease after a median
      follow-up of 66 months (range, 31-134 months). Three prognostic factors were
      found to be significant in the univariate analysis for unfavorable outcome: the
      presence of pure embryonal carcinoma in the primary tumor, liver metastases
      measuring > 30 mm in greatest dimension at the time of surgery, and the presence
      of viable, active residual disease. CONCLUSIONS: Because it is impossible to
      determine the histologic pattern of residual liver masses after chemotherapy with
      current imaging tools and percutaneous biopsy, patient selection for liver
      surgery may be undertaken according to the size of residual liver masses.
      Patients with masses that measure < or = 10 mm in greatest dimension should be
      considered for close follow-up, because they have a high probability of necrosis
      and are at low risk for malignant disease. Male patients with masses that measure
      > or = 30 mm in greatest dimension represent a high-risk group of patients who
      are not likely to benefit from liver surgery. Only male patients with masses that
      measure 10-29 mm in greatest dimension and all female patients with masses that
      measure > 10 mm in greatest dimension should be considered for liver resection.

PMID- 11505403
TI  - A case-control study for evaluating the efficacy of mass screening program for
      lung cancer in Miyagi Prefecture, Japan.
AB  - BACKGROUND: In Miyagi Prefecture, Japan, a mass screening program for lung cancer
      has been conducted since 1982 (miniature chest X-ray for all screenees and sputum
      cytology for those with a smoking index > or = 600) [smoking index 600 = 30 pack
      years, the average number of cigarettes smoked per day multiplied by the number
      of years of regular smoking]. Over 1500 lung carcinomas, including 250
      roentgenographically occult lung tumors, were detected and treated up to 1999. In
      the current study, a nested case-control study was conducted in the population
      that was screened in 1989 to evaluate the efficacy of the screening program for
      lung cancer. METHODS: To reduce self-selection bias, the source population was
      defined as screenees with negative results in 1989 (284,226 individuals). In the
      population, 474 individuals died of lung carcinoma during 1992-1994. After
      exclusion, 328 patients who died of primary lung carcinoma at between ages 40
      years and 79 years were defined as the cases. Six controls were supposed to be
      selected in the source population for each case and matched by gender, year of
      birth, municipality, and smoking habits. Controls who had died or moved before
      the matched case was diagnosed were excluded. Finally, 328 cases and 1886
      controls were selected. Screening histories were compared, and odds ratios were
      calculated using conditional logistic regression analysis. RESULTS: Within the 12
      months before diagnosis, 241 of 328 cases (73.5%) had attended the screening
      compared with 1557 of 1886 controls (82.6%). The smoking-adjusted odds ratio was
      0.54 (95% confidence interval, 0.41-0.73). CONCLUSIONS: The mass screening
      program for lung cancer in Miyagi Prefecture was capable of reducing by 46% the
      risk of death from carcinoma of the lung.

PMID- 11505404
TI  - Phase II study of pemetrexed disodium, a multitargeted antifolate, and cisplatin
      as first-line therapy in patients with advanced nonsmall cell lung carcinoma: a
      study of the National Cancer Institute of Canada Clinical Trials Group.
AB  - BACKGROUND: Pemetrexed disodium (Alimta [Eli Lilly and Company, Indianapolis,
      IN], LY231514, multitargeted antifolate) is a new multitargeted antifolate agent
      that inhibits multiple enzymes in the folate pathway. Phase II trials showed
      single-agent response rates of 16% and 23% in untreated patients with nonsmall
      cell lung carcinoma (NSCLC). This study was undertaken to determine the response
      to pemetrexed disodium given in combination with cisplatin. METHODS: Previously
      untreated patients were eligible if they had Stage IIIB or IV NSCLC, performance
      status 0, 1, or 2, adequate hematology and biochemistry and bidimensionally
      measurable lesions. Patients with brain metastases or neuropathy higher than
      Grade 2 were excluded. Pemetrexed disodium 500 mg/m(2) was given over 10 minutes,
      and cisplatin 75 mg/m(2) with hydration and mannitol diuresis was administered on
      Day 1 of each 21-day cycle. Dexamethasone 4 mg was taken orally once every 12
      hours starting 24 hours before treatment and continuing for 6 doses after
      treatment. Four patients had detailed pemetrexed disodium pharmacokinetic
      analysis performed. RESULTS: Between May 1998 and June 1999, 31 patients were
      treated on the study. There were 20 males and 11 females; median age was 60 years
      (range, 35-75 years); there were 5 Stage IIIB, 26 Stage IV, 26 performance status
      0 or 1, and 5 performance status 2. In 29 patients evaluable for response, there
      were 13 partial responses (PRs; overall response rate [ORR], 95%; confidence
      interval [CI]: 26-64%) of median duration 6.1 months (1.6-7.8 months). Three of
      four evaluable patients with performance status 2 achieved PR, and 11 of 24
      evaluable Stage IV patients responded (ORR, 45.8% in Stage IV). Eighteen patients
      died. The median survival rate was 8.9 months (range, 1-15+ months). A total of
      160 courses were delivered (median, 6 for both cisplatin and pemetrexed
      disodium). Grade 3 and 4 anemia was observed in 5 and 1 patients, respectively,
      and Grade 3 and 4 granulocytopenia in 7 and 4 patients, respectively. Grade 3
      nausea and emesis occurred in only 2 patients, Grade 3/4 diarrhea in 3 patients,
      and 2 patients had Grade 3 motor neuropathy. Nine patients had Grade 2
      infections, and there was one case of febrile neutropenia. Pharmacokinetic
      results showed C(max), clearance and V(ss) values to be similar to data from
      single-agent pemetrexed disodium given in the same dose. CONCLUSIONS: The
      combination of pemetrexed disodium and cisplatin is active against advanced NSCLC
      and is a well-tolerated convenient outpatient regimen. It deserves further study
      to compare it with other standard regimens for NSCLC.

PMID- 11505405
TI  - Randomized phase II study of cyclophosphamide, doxorubicin, and vincristine
      compared with single-agent carboplatin in patients with poor prognosis small cell
      lung carcinoma.
AB  - BACKGROUND: Information on the effect of chemotherapy in a group of patients with
      poor prognosis, poor performance status small cell lung carcinoma (SCLC) is
      scarce. A randomized study comparing single-agent carboplatin with combination
      chemotherapy in this largely unreported population of SCLC patients was
      undertaken. METHODS: One hundred nineteen patients were allocated to four cycles
      of either cyclophosphamide, doxorubicin, and vincristine (CAV) or single-agent
      carboplatin. Patients had either a Karnofsky performance score < or = 50 and/or a
      prognostic score indicative of a 1-year survival rate < or = 15%. RESULTS: Grade
      3-4 neutropenia and intravenous antibiotic use were significantly more common
      with the CAV regimen (P < 0.005). Conversely, Grade 3-4 thrombocytopenia was more
      common (P < 0.0009) and platelet transfusion was more frequent (P < 0.05) with
      carboplatin therapy. Nonhematologic toxicity was similar in both treatment arms,
      except for alopecia with CAV therapy (P < 0.0007). Symptom relief occurred in 48%
      and 41% of patients in the CAV and carboplatin treatment arms, respectively.
      Dyspnea was improved in 66% and 41% of patients and cough was improved in 21% and
      7% of patients in the CAV and carboplatin treatment arms, respectively. CAV
      therapy produced a higher response rate than carboplatin (38% vs. 25%), but this
      was not statistically significant (P = 0.15). The median overall survival for
      patients in the CAV and carboplatin treatment arms was 17 weeks and 15.9 weeks,
      respectively, with 1-year survival rates of 12% and 6%. CONCLUSIONS: Single-agent
      carboplatin is a feasible treatment in patients with poor prognosis SCLC and
      produces response rates, relief of tumor-related symptoms, and survival similar
      to what is seen in patients who receive CAV chemotherapy. The lower risk of life
      threatening sepsis and less need for hospitalization or intravenous antibiotic
      courses is advantageous in this susceptible patient population.

PMID- 11505406
TI  - High-dose tamoxifen added to concurrent biochemotherapy with decrescendo
      interleukin-2 in patients with metastatic melanoma.
AB  - BACKGROUND: In vitro cell culture data and preclinical models suggest that
      tamoxifen modulates tumor cell sensitivity to a wide range of therapeutic agents.
      In the current study, the authors examined whether high-dose tamoxifen (HDT)
      improved the overall and complete response in patients with metastatic melanoma
      who were treated with concurrent biochemotherapy. METHODS: Forty-nine patients
      were treated with a biochemotherapy regimen of dacarbazine, vinblastine,
      cisplatin, decrescendo interleukin-2, interferon-alpha-2b, and tamoxifen. The
      study had a 2-step design, beginning with a tamoxifen dose escalation from 40 mg
      to 320 mg (17 subjects) to evaluate safety and tolerability, followed by Phase II
      accrual of 32 patients to HDT (320 mg) to assess clinical efficacy. Efficacy was
      compared with a similar modified biochemotherapy regimen with low-dose tamoxifen
      (LDT). Pharmacokinetic studies were performed to determine in vivo tamoxifen
      levels. RESULTS: Tamoxifen dose escalation was completed without any reported
      dose-limiting toxicity. The overall response rate in the HDT group was 50% (95%
      confidence interval, 33.2%-66.8%), with a complete response rate of 6% and a
      median survival of 9.5 months. The overall response rate was not improved and the
      complete response and survival appeared inferior compared with that of patients
      recently treated with concurrent biochemotherapy and LDT. Serum tamoxifen levels
      were found to correlate with the dose administered, with a mean of 0.9 microM at
      the 40-mg dose to 4.6 microM at the 320-mg dose. Ultrafiltered protein-free sera
      demonstrated low (< 0.01 microM) concentrations of tamoxifen. CONCLUSIONS: The
      addition of HDT to a regimen of concurrent biochemotherapy did not appear to
      improve response rates or overall survival, despite reaching the targeted plasma
      concentration. Unknown drug interactions or high protein binding of tamoxifen may
      account for the lack of clinical effectiveness.

PMID- 11505407
TI  - Tumor necrosis factor alpha negatively regulates the expression of the carcinoma
      associated antigen epithelial cell adhesion molecule.
AB  - BACKGROUND: The epithelial cell adhesion molecule (EpCAM) is a homophilic and
      Ca2+ independent adhesion molecule that is expressed de novo in squamous cell
      carcinoma (SCC) but is absent in the majority of healthy squamous epithelia.
      EpCAM expression correlates with cell proliferation and dedifferentiation along
      with a progression in tumorigenicity. To date, nothing is known about the
      molecular mechanisms responsible for the regulation of the EpCAM gene. METHODS:
      The authors analyzed the regulation of a fragment of the EpCAM promoter. RESULTS:
      The analyzed fragment has significant activity in EpCAM positive cells, and it is
      regulated negatively by tumor necrosis factor alpha (TNFalpha). This negative
      regulation results in diminished mRNA expression and in the down-regulation of
      EpCAM protein at the cell surface in SCC cells. Both effects can be mimicked by
      the treatment of cells with the phorbol ester 12-O-tetradecanoylphorbol-13
      acetate (TPA). TNFalpha-induced inhibition of the EpCAM expression is mediated by
      TNF receptor 1 through the TNF receptor-associated death domain protein (TRADD)
      and by the activation of nuclear factor kappaB (NF-kappaB), and it can be blocked
      by dominant-negative variants of TRADD and the NF-kappaB inhibitor, IkappaB. The
      authors provide further evidence that NF-kappaB represses EpCAM expression by
      competing for the transcriptional coactivator p300/CREB binding protein
      (p300/CBP). CONCLUSIONS: The current results provide the first insights into the
      regulation of EpCAM expression, which is regulated negatively by TNFalpha and TPA
      through the activation of NF-kappaB. The repression may rely on the competition
      of NF-kappaB for p300/CBP histone acetyl transferase activity, because the
      overexpression of p300 reverts TNFalpha effects.

PMID- 11505409
TI  - Expression of glucose transporter-1 in human gastric carcinoma: association with
      tumor aggressiveness, metastasis, and patient survival.
AB  - BACKGROUND: Malignant cells show increased glucose uptake in vitro and in vivo,
      which is believed to be facilitated by glucose transporters (Gluts). Expression
      of Glut1, one of the Gluts, has been described in malignancies of the esophagus,
      colon, pancreas, lung, and brain, but to the authors' knowledge the significance
      of Glut1 expression in human gastric carcinoma has not been elucidated. The
      objective of the current study was to examine the expression and distribution of
      Glut1 and its relation to clinicopathologic parameters in patients with gastric
      carcinoma. METHODS: Immunohistochemistry with anti-Glut1 antibody was performed
      on 617 gastric carcinomas and 50 tubular adenomas of the stomach. Glut1-positive
      and Glut1-negative carcinomas were analyzed for their clinicopathologic
      characteristics including histologic subtype, depth of invasion, vascular
      permeation, lymph node and hepatic metastasis, peritoneal dissemination, and
      prognosis. RESULTS: None of the adenomas expressed Glut1, whereas 182 of 617
      carcinomas (29.5%) were positive for the protein. Signet ring cell carcinoma and
      mucinous adenocarcinoma rarely were positive (2.0% and 6.3%, respectively) and
      papillary adenocarcinoma (44%) showed slightly higher positivity for Glut1 than
      tubular (32%) or poorly differentiated adenocarcinoma (28%). Glut1-positive tumor
      cells were localized mainly in the central part of tumor nests with or without
      peripheral distribution (92%) but peripheral distribution alone was very limited
      (8%) (P = 0.0001). Glut1 positivity was associated with depth of invasion (P =
      0.0001), lymphatic permeation (P = 0.0001), venous invasion (P = 0.0001), lymph
      node metastasis (P = 0.0001), hepatic metastasis (P = 0.0001), and carcinoma
      stage (P = 0.0001). However, peritoneal dissemination was not found to be
      associated with Glut1 positivity (P = 0.0833). The survival of patients who had
      tumors that expressed Glut1 was significantly shorter than that of patients with
      Glut1-negative tumors (P = 0.0001). CONCLUSIONS: In human gastric carcinoma,
      Glut1 is expressed late in carcinogesis and increases with disease progression.
      Glut1 expression is associated with tumor aggressiveness and patient survival.

PMID- 11505408
TI  - Neuropeptide Y, leptin, and cholecystokinin 8 in patients with advanced cancer
      and anorexia: a North Central Cancer Treatment Group exploratory investigation.
AB  - BACKGROUND: Anorexia is a noxious symptom, and over half of patients with
      advanced cancer experience it. Neuropeptide Y (NPY), leptin, and cholecystokinin
      8 (CCK8) have been implicated. METHODS: This exploratory study 1) compared
      circulating concentrations of NPY and leptin between anorectic cancer patients
      and historic controls and 2) explored whether NPY, leptin, or CCK8 may serve as
      correlates of anorexia severity. Cancer patients met predefined eligibility
      criteria: 1) weight loss > or = 2.3 kg over the preceding 2 months and/or a
      physician-estimated caloric intake of < 20 calories per kilogram of body weight
      per day and 2) patient acknowledgment that appetite or weight loss was an ongoing
      problem. RESULTS: Seventy-three cancer patients were studied, and > 90% reported
      a > or = 50% decline in appetite from baseline in the preceding 2 months. NPY
      levels were lower than control values: mean +/- standard deviation, 466 pg/mL +/-
      161 pg/mL versus 560 pg/mL +/- 151 pg/mL, respectively (P = 0.004). Because a few
      (but not all) earlier studies suggested an age-related decline in NPY levels, a
      subgroup analysis was performed and found no age-adjusted difference in NPY
      levels between groups. Similarly, leptin concentrations were not different
      between groups. Significant correlations were not observed between anorexia
      severity and NPY, leptin, or CCK8 levels. CONCLUSIONS: There were no differences
      in leptin and CCK8 levels between anorectic cancer patients and historic
      controls. Circulating concentrations of NPY, leptin, and CCK8 did not correlate
      with anorexia severity. However, the current results suggest a need for further
      examination of NPY in cancer-associated anorexia.

PMID- 11505410
TI  - Paclitaxel, carboplatin, and long-term continuous infusion of 5-fluorouracil in
      the treatment of advanced squamous and other selected carcinomas: results of a
      Phase II trial.
AB  - BACKGROUND: The purpose of this study was to evaluate the feasibility, toxicity,
      and efficacy of the combination of paclitaxel, carboplatin, and long-term
      continuous infusion 5-fluorouracil (5-FU) in the treatment of advanced squamous
      carcinomas of various primary sites. METHODS: Patients were eligible for this
      trial if they had metastatic squamous carcinoma at any site except the lung. In
      addition, patients with locally advanced squamous carcinoma of the head and neck
      were eligible, if they were considered unlikely to be cured with combined
      modality therapy. Sixty patients entered this trial between February 1995 and
      March 1999; 12 patients (20%) had received 1 previous chemotherapy regimen,
      whereas 48 patients (80%) were previously untreated. All patients received the
      following regimen: paclitaxel 200 mg/m(2), 1-hour intravenous infusion, Days 1
      and 22; carboplatin area under the concentration-time curve (AUC) 6.0
      intravenously, Days 1 and 22; 5-FU 225 mg/m(2)/day, by 24-hour continuous
      intravenous infusion, Days 1-35. Treatment courses were repeated at 6-week
      intervals; responding patients continued treatment for a maximum of 4 courses (24
      weeks). RESULTS: Thirty-nine of 60 patients treated (65%) had objective responses
      to this regimen, with 25% complete responses. Twelve patients (22%) remain
      progression free from 7 to 63 months (median, 35 months) after completion of
      therapy. Complete responses were observed in squamous carcinomas from various
      primary sites including head and neck, esophagus, cervix, vagina, anus, and
      unknown primary. The most frequent Grade 3/4 toxicities observed with this 3-drug
      regimen included leukopenia (48%), diarrhea (17%), mucositis (28%), and portacath
      related events (13%). CONCLUSIONS: The combination of paclitaxel, carboplatin,
      and long-term infusional 5-FU is feasible, well tolerated, and highly efficacious
      in patients with advanced squamous carcinomas of various primary sites. This
      regimen merits further investigation.

PMID- 11505411
TI  - Combined regimen of cisplatin, doxorubicin, and alpha-2b interferon in the
      treatment of advanced malignant pleural mesothelioma: a Phase II multicenter
      trial of the Italian Group on Rare Tumors (GITR) and the Italian Lung Cancer Task
      Force (FONICAP).
AB  - BACKGROUND: The cisplatin-doxorubicin combination has shown moderate activity in
      malignant pleural mesothelioma (MPM; objective response, 25%), and preclinical
      studies suggest that interferons (IFNs) may have an antiproliferative effect on
      mesothelioma cell lines with a marked increase in cisplatin cytotoxicity.
      Therefore, the combined chemoimmunotherapy regimen is an worthwhile approach to
      evaluate in a Phase II trial. METHODS: From December 1995 to June 1999, 37
      previously untreated patients with MPM were treated with cisplatin 60 mg/m(2)
      intravenously on Day 1 plus doxorubicin 60 mg/m(2), recycled every 3-4 weeks and
      IFN-alpha-2b, 3 x 10((6)) international units subcutaneously 3 times a week for a
      total of 6 courses or until progression. Inclusion criteria were histologic
      diagnosis of MPM and measurable disease defined by computed tomography scan or
      magnetic resonance imaging. RESULTS: Thirty-four patients were assessable for
      toxicity and 35 for efficacy according to World Health Organization criteria. One
      hundred thirty-five courses were administered with a median of 4 cycles per
      patients. Seventy-six percent of patient presented at least 1 episode of severe
      myelosuppression (Grade 3 and 4). Severe anemia and thrombocytopenia occurred in
      30% and 24% of patients, respectively. Sixty percent of patients presented
      constitutional symptoms. In the 35 patients assessable for response, the overall
      response rate was 29% (95% confidence interval, 15-47%). The median duration of
      response was 8.4 months. With a median follow-up of 19.6 months, the median
      survival was 9.3 months. One- and 2-year survival was 45% and 34%, respectively.
      CONCLUSIONS: This combined regimen has definite activity in MPM. However,
      toxicity, particularly myelosuppression and fatigue, is not negligible and may
      limit its application.

PMID- 11505412
TI  - Germline mutation in the juxtamembrane domain of the kit gene in a family with
      gastrointestinal stromal tumors and urticaria pigmentosa.
AB  - BACKGROUND: Gain-of-function mutations of the c-kit protooncogene, mainly
      clustered in the juxtamembrane domain, have been reported in a significant
      fraction of gastrointestinal (GI) stromal tumors (GISTs) that represent the most
      common mesenchymal tumor of the GI tract. Two families also have been described
      with a GIST predisposition syndrome with a germline c-kit mutation affecting
      either the juxtamembrane domain or the tyrosine kinase domain. Here, the authors
      report on a family in which the dominantly inherited trait of hyperpigmented
      spots was inherited from an individual who developed multiple GISTs with diffuse
      hyperplasia of the myenteric plexus by his son, who was affected with urticaria
      pigmentosa. METHODS: Screening for the c-kit mutation was performed by means of
      polymerase chain reaction-based denaturing gradient gel electrophoresis/constant
      denaturing gel electrophoresis followed by direct sequencing of abnormal
      conformers. Expression of KIT and CD34 was determined by immunohistochemistry.
      RESULTS: In peripheral blood DNA samples, both affected family members showed a
      previously undescribed c-kit mutation in the juxtamembrane domain, resulting in
      the substitution of alanine for valine(559). Mutation and polymorphic marker
      analyses on DNA samples from three GISTs and two skin biopsy specimens evidenced
      the same mutation in the heterozygous condition. Immunohistochemical examination
      showed coexpression of CD117 (c-kit) and CD34 in all independent GISTs and CD117
      positivity in mast cells from the skin lesions. CONCLUSIONS: Comparative analysis
      of clinical presentation and mutation mapping in the families described to date
      point to the peculiar association of mast cells, melanocytic dysfunction, and
      GIST predisposition in carriers of c-kit mutations within the juxtamembrane
      domain.

PMID- 11505413
TI  - Clinical significance of serum vascular endothelial growth factor in esophageal
      squamous cell carcinoma.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF) is a potent inducer of
      angiogenesis in malignant tumors. An increased in the serum VEGF concentration (S
      VEGF) has been found in patients with various solid tumors and appears to be
      correlated with tumor burden. The objective of the current study was to determine
      the correlation between pretreatment S-VEGF and clinicopathologic features in
      patients with esophageal squamous cell carcinoma. METHODS: Pretreatment S-VEGF
      was measured by enzyme-linked immunoadsorbent assay in 24 healthy controls and 96
      patients with esophageal squamous cell carcinoma (82 patients with primary tumors
      and 14 with recurrent tumors). Chemoradiotherapy was performed in 35 patients
      followed by response evaluation. RESULTS: S-VEGF was found to be significantly
      elevated in patients with primary esophageal carcinoma (P = 0.0011). Significant
      differences were observed when S-VEGF was categorized by tumor size (P = 0.0002),
      tumor depth (P = 0.0082), lymph node metastasis (P = 0.0002), distant metastasis
      (P = 0.028), and International Union Against Cancer TNM stage (P < 0.0001). The
      patients who achieved a partial or complete response to chemoradiotherapy showed
      significantly less S-VEGF than those patients who were nonresponders (P = 0.018).
      A high (> 451 pg/mL) S-VEGF level was associated with poor survival (P < 0.001).
      Multivariate analysis found S-VEGF to be a significant and independent prognostic
      factor (P < 0.001). CONCLUSIONS: In the current study, a high S-VEGF was found to
      be associated with tumor progression, poor treatment response, and poor survival
      in patients with squamous cell carcinoma of the esophagus.

PMID- 11505414
TI  - Treatment of unicentric and multicentric Castleman disease and the role of
      radiotherapy.
AB  - BACKGROUND: Although surgery is considered standard therapy for unicentric
      Castleman disease, favorable responses to radiotherapy also have been documented.
      The authors undertook this study to analyze the clinical factors, treatment
      approaches, and outcomes of patients with unicentric or multicentric Castleman
      disease, and to report the outcomes of patients with unicentric Castleman disease
      treated with radiotherapy. METHODS: The authors reviewed the medical records of
      22 patients who had received a histologic diagnosis of Castleman disease at the
      University of Texas M. D. Anderson Cancer Center between 1988 and 1999. One
      patient with a concurrent histopathologic diagnosis of nonsecretory multiple
      myeloma was excluded from the study. In all patients, the diagnosis of Castleman
      disease was based on the results of lymph node biopsies. Disease was categorized
      as being either unicentric or multicentric and further subdivided into hyaline
      vascular, plasma cell, or mixed variant histologic types. Clinical variables and
      outcomes were analyzed according to treatment, which consisted of surgery,
      chemotherapy, or radiotherapy. RESULTS: Records from 21 patients were analyzed:
      12 had unicentric disease, and 9 had multicentric disease. The mean follow-up
      time for the entire series was 51 months (median, 40 months). Four patients with
      unicentric disease were treated with radiotherapy alone: 2 remain alive and
      symptom free, 2 died of causes unrelated to Castleman disease and had no evidence
      of disease at last follow-up. Eight patients with unicentric disease were treated
      with complete or partial surgical resection, and all are alive and asymptomatic.
      All nine patients with multicentric disease were treated with combination
      chemotherapy: five are alive with no evidence of disease, and four are alive with
      progressive disease. CONCLUSIONS: Surgery results in excellent rates of cure in
      patients with unicentric Castleman disease; radiotherapy can also achieve
      clinical response and cure in selected patients. Multicentric Castleman disease
      is a more aggressive clinical entity and is most effectively treated with
      combination chemotherapy, whereas the role of radiotherapy in its treatment
      remains unclear.

PMID- 11505415
TI  - Amplification of the HER-2/neu oncogene is uncommon in pediatric osteosarcomas.
AB  - BACKGROUND: Recent reports have described overexpression of p185(c-erbB2), the
      product of the HER-2/neu oncogene, in more than 40% of archival osteosarcomas
      that were examined by immunohistochemistry (IHC). However, IHC can be influenced
      by the method of fixation, extent of antigen retrieval, specificity and
      sensitivity of the antibody clone, and the use of an arbitrary semiquantitative
      scoring system. In contrast, fluorescence in situ hybridization (FISH) assays
      that assess HER-2/neu gene copy numbers in individual cells are more consistent,
      more reproducible, and less subjective than IHC. METHODS: The authors examined
      pretreatment nondecalcified archival tissue from 21 high-grade pediatric
      osteosarcomas for amplification of the HER-2/neu oncogene using an Food and Drug
      Administration (FDA)-approved FISH assay (PathVysion, Vysis Inc., Downers Grove,
      IL). Additionally, IHC for p185(c-erbB2) was performed in all cases using the
      Dako polyclonal antibody clone A0485 (Dako Co., Carpinteria, CA). RESULTS: None
      of the 21 osteosarcomas had evidence of HER-2/neu gene amplification by FISH,
      whereas p185(c-erbB2) IHC was negative in all cases. CONCLUSIONS: HER-2/neu gene
      amplification appeared to be an uncommon event in pediatric osteosarcomas. The
      reason(s) for discordance between previous IHC data and the current FISH and IHC
      results was unknown, but might reflect intrinsic variations in antibody clones,
      or might suggest that, in some cases, the occurrence of protein overexpression is
      independent of gene amplification.

PMID- 11505416
TI  - A randomized, controlled clinical trial of the homeopathic medication TRAUMEEL S
      in the treatment of chemotherapy-induced stomatitis in children undergoing stem
      cell transplantation.
AB  - BACKGROUND: Stomatitis is a common consequence of chemotherapy and a condition
      for which there is little effective treatment. Although the management of
      patients with other chemotherapy-related toxicities has improved in recent years,
      the incidence of stomatitis is increasing because of more intensive treatment and
      is often a dose limiting factor in chemotherapy. The authors assessed the
      efficacy of a homeopathic remedy, TRAUMEEL S(R), in the management of
      chemotherapy-induced stomatitis in children undergoing bone marrow
      transplantation. METHODS: A randomized, placebo-controlled, double-blind clinical
      trial was conducted in 32 patients ages 3-25 years who had undergone allogeneic
      (16 patients) or autologous (16 patients) stem cell transplantation. Of the 30
      evaluable patients, 15 were assigned placebo, and 15 were assigned TRAUMEEL S
      both as a mouth rinse, administered five times daily from 2 days after
      transplantation for a minimum of 14 days, or until at least 2 days after all
      signs of stomatitis were absent. Stomatitis scores were evaluated according to
      the World Health Organization grading system for mucositis. RESULTS: A total of
      five patients (33%) in the TRAUMEEL S treatment group did not develop stomatitis
      compared with only one patient (7%) in the placebo group. Stomatitis worsened in
      only 7 patients (47%) in the TRAUMEEL S treatment group compared with 14 patients
      (93%) in the placebo group. The mean area under the curve stomatitis scores were
      10.4 in the TRAUMEEL S treatment group and 24.3 in the placebo group. This
      difference was statistically significant (P < 0.01). CONCLUSIONS: This study
      indicates that TRAUMEEL S may reduce significantly the severity and duration of
      chemotherapy-induced stomatitis in children undergoing bone marrow
      transplantation.

PMID- 11505417
TI  - Informed consent for pediatric leukemia research: clinician perspectives.
AB  - BACKGROUND: Good, fully informed consent is critical to the ethical conduct of
      clinical cancer research. The authors examined clinician perspectives on informed
      consent for pediatric research by surveying clinicians at five major medical
      centers that routinely enroll patients in Children's Cancer Group studies.
      METHODS: Building on a pilot study, a questionnaire was designed to elicit
      clinicians' general opinions, approaches, and suggestions related to informed
      consent in pediatric leukemia trials. Questionnaires were mailed to 132
      clinicians. Eighty-nine questionnaires were returned, along with 13
      nonparticipant forms notifying us of the clinician's inability to participate
      because of a lack of experience in pediatric informed consent. The response rate
      was 75%. RESULTS: Providing information so that families can decide about study
      entry was ranked as the most important goal of the informed consent process,
      whereas parents' state of shock was rated the most significant obstacle to good
      informed consent. Clinicians cited high levels of parental comprehension of key
      aspects of clinical research studies and reported information overload and
      increased anxiety as effects of the informed consent process on parents. Several
      key items were associated with clinicians' gender, race, and professional
      experience. Finally, one open-ended question yielded 126 suggestions for how to
      improve the informed consent process that were grouped into 10 meaningful
      categories. CONCLUSIONS: Clinicians report a range of approaches, opinions,
      concerns, and suggestions for improving the informed consent process. The article
      proposes that their views and suggestions be integrated with those of parents and
      patients in attempts to survey and improve informed consent in pediatric
      oncology.

PMID- 11505418
TI  - Clinicopathologic assessment and grading of embolized meningiomas: a correlative
      study of 64 patients.
AB  - BACKGROUND: Preoperative embolization of meningiomas is commonly performed to
      minimize intraoperative bleeding, thereby facilitating surgery and reducing the
      necessity for transfusion. However, the resulting necrosis and compensatory
      proliferation reportedly have hampered subsequent histologic grading. METHODS:
      The clinicopathologic features of 64 meningiomas embolized between 1989 and 1997
      were assessed. Tumors were graded according to recently published criteria.
      RESULTS: A good embolization result (> 75% reduction in angiographic blush) was
      achieved in 52%. Histologically, embolized meningiomas showed higher frequencies
      of necrosis (89%), nuclear atypia (72%), macronucleoli (58%), sheeting (31%),
      high mitotic index (30%), and brain invasion (14%) when compared with
      nonembolized counterparts. Median mitotic and MIB-1 indices were slightly
      elevated (1.5 of 10 high-power fields and 1.6%, respectively). A significant
      degree of necrosis (> 10%) was found in 43% and was only roughly correlated with
      extent of angiographic blush reduction or embolization particle size. Histologic
      grade was benign in 57.8%, atypical in 40.6%, and anaplastic in 1.6%. At last
      follow-up, there were 13 recurrences, 11 in the atypical/anaplastic (41%) versus
      2 in the benign (5%) subsets (P = 0.001). CONCLUSIONS: The authors conclude that
      1) their grading scheme accurately stratifies embolized meningiomas, 2) extent of
      necrosis is difficult to predict using standard clinical parameters, and 3) their
      high incidence of atypical meningioma more likely reflects patient selection
      biases rather than artifacts induced by the embolization procedure.

PMID- 11505419
TI  - Special report: NIST workshop on reference data for the properties of
      biomaterials.
AB  - A workshop on Reference Data for Biomaterials was held at the National Institute
      of Standards and Technology (NIST) on July 27, 2000. The primary purpose of the
      workshop was to determine whether needs existed for the establishment of
      reference data (RD) databases on the properties of biomaterials. Special
      attention was given to critiqued RD such as those traditionally found in
      databases that are established within the NIST Standard Reference Data Program.
      Critiqued data are data that have been critically evaluated for issues dealing
      with components of uncertainty, experimental design (details, descriptions, and
      appropriateness), measurement methods (appropriateness), conclusions drawn from
      the data, and so forth. Among the workshop's 65 registrants were representatives
      from industry, the National Institutes of Health (NIH), the Food and Drug
      Administration (FDA), and academia. These joined with NIST staff to address
      reference biomaterial property database needs within five categories: orthopedic,
      cardiovascular, ophthalmologic, tissue-engineered, and dental biomaterials. A
      general session on other issues focused specifically on database accesses
      (portals), contents, and maintenance. While the workshop's intended focus was on
      critiqued RD, it was suggested that closely related issues be considered as well.
      In this way, a more comprehensive assessment of opportunities for the cooperation
      of NIST with the biomaterials community might be developed. As a result, the
      needs for noncritiqued data and for reference materials (RMs), useful for
      developing data, also became a part of the focus of the workshop. Hence, this
      article presents the results from the breakout sessions of the workshop according
      to two categories: reference data and databases, and reference materials. In the
      following summary, the workshop is presented in the following order: An
      introduction to databases, resource presentations, action items identified in
      breakout sessions, assessment of resources (personnel and monetary) needed to
      work on action items, and portals for databases. Except for the individual
      concurrent breakout sessions themselves, all other sessions of the workshop were
      participated in fully by those in attendance.

PMID- 11505420
TI  - Hemocompatibility, biocompatibility, inflammatory and in vivo studies of primary
      reference materials low-density polyethylene and polydimethylsiloxane: a review.
AB  - In 1984, low-density polyethylene (LDPE) and polymethylsiloxane (PDMS), two
      primary reference materials (PRM), were made available by the National Heart,
      Lung, and Blood Institute (NHLBI) as discriminatory tools for the validation of
      standardized and novel in vitro and in vivo tests in the evaluation of
      biomaterials. This article reviews the results and conclusions obtained by
      several studies investigating the hemocompatibility, in vitro biocompatibility,
      inflammatory response, and in vivo tissue reactions of these two reference
      materials. Variable results obtained with LDPE and PDMS in ex vivo
      hemocompatibility studies were attributed to the type of animal model used, the
      flow velocity of the circulating blood, the time of exposure, and the methodology
      used to measure blood cell adhesion or activation at the surface of the
      materials. In contrast, both the LDPE and PDMS appeared to be suitable reference
      materials when used in in vitro biocompatibility, inflammatory response, and in
      vivo studies. However, caution must be taken when interpreting the results,
      because gamma sterilization of these two materials as well as their origin (for
      example PDMS) are two critically important factors. In conclusion, we see a
      definite need for standardized hemocompatible parameters and better high-quality
      hemocompatibility studies on PRM. This review also suggests other materials as
      potential PRM candidates, namely, Biomer and Intramedic polyethylene.

PMID- 11505421
TI  - Calcium-phosphate surface coating by casting to improve bioactivity of titanium.
AB  - In order to improve the bioactivity of titanium, an original surface treatment
      was attempted with the use of a casting technique was attempted. Pure titanium
      was cast into a special graphite mold in which the cavity wall was coated with
      hydroxyapatite (HA) powder. According to analyses of X-ray diffraction and EDX,
      the existence of HA and CaO and uptake of Ca and P on the surface of the titanium
      castings were identified. By immersing the specimen in Hank's solution, the
      concentrations of Ca and P on the surface increased with immersion time, and the
      formation of a thin layer with characteristics of spherical HA precipitates was
      observed after 1 week. The concentrations of Ca and P elements and the Ca/P ratio
      on the HA layer increased with immersion time. The formation of the HA layer on
      the titanium cast by this treatment was significantly accelerated compared with
      pure titanium. The present surface treatment of Ti is expected to improve early
      bone fixation of Ti implants.

PMID- 11505422
TI  - Comparison of the biomechanics and histology of two soft-tissue fixators composed
      of bioabsorbable copolymers.
AB  - The purpose of this study was to assess the dynamic in vitro and in vivo
      characteristics of two different bioabsorbable copolymer soft-tissue fixation
      devices and to determine their efficacy in reattaching soft tissue to bone.
      Suretac fixators (Smith & Nephew/Acufex MicroSurgical Inc., Northwood, MA), made
      of polyglyconate (2:1 glycolic acid:trimethylene carbonate), and Pop Rivets
      (Arthrotek, Warsaw, IN), made of LactoSorb (82% poly L-lactic acid, 18%
      polyglycolic acid), were anchored into synthetic bone, and their pull-out
      strengths were evaluated. The devices were also evaluated with the use of an in
      vivo goat model in which the medial collateral ligament (MCL) was elevated from
      the tibia and directly reattached. In the in vitro biomechanical study, the
      Suretac fixators had negligible strength remaining by four weeks, whereas the Pop
      Rivets retained 50% of their strength at 4 weeks, 20% at 8 weeks, and negligible
      strength at 12 weeks. The in vivo strength of MCL repairs affected by each
      implant was not statistically different at any of the time points.
      Histologically, both implants were absorbed by 52 weeks, and there was no
      appreciable adverse tissue response. In conclusion, both copolymer fixators were
      found to be biocompatible. The Pop Rivet fixators demonstrated in vivo
      performance comparable to the Suretac fixators, although the Pop Rivets retained
      strength longer in vitro. Our results suggest that both devices provide adequate
      strength of fixation before degrading to allow the healing soft tissues to reach
      or surpass their native strength.

PMID- 11505423
TI  - Effects of in vitro wear of machined and molded UHMWPE tibial inserts on TKR
      kinematics.
AB  - The effect of manufacturing process on the wear and mechanical performance of a
      total knee replacement (TKR) design was investigated with the use of a force
      controlled knee joint simulator. Ultra-high molecular weight polyethylene
      (UHMWPE) tibial inserts processed by direct compression molding from 1900H resin
      were compared to UHMWPE tibial inserts machined from a compression-molded sheet
      of GUR 1050. Both sets of components had the same posterior-cruciate-retaining
      geometry, and were identically aligned with cobalt-chromium-molybdenum alloy
      femoral components. Wear tests were conducted at a frequency of 1 Hz for 4
      million cycles with the use of a standard walking cycle pattern. Implant
      kinematics, including anterior-posterior (AP) displacement and internal-external
      (IE) rotation in response to applied loads were monitored. Gravimetric wear,
      surface roughness, and surface morphology were used to characterize the wear
      process of the UHMWPE inserts. Results showed that the molded UHMWPE inserts
      exhibited less gravimetric wear over time than the machined inserts of the same
      design. Both the machined and molded components exhibited scratching, pitting,
      and burnishing over their wear areas. The AP displacement distance per cycle of
      the molded tibial inserts decreased over the course of testing, resulting in a
      shorter total testing displacement for this group compared to machined tibial
      inserts. Although AP displacement distance per cycle for machined tibial inserts
      did not change significantly over the course of testing, their position relative
      to the femoral components shifted posteriorly over time, resulting in an
      elongated wear track.

PMID- 11505424
TI  - Assessment of parameters associated to the risk of PVC catheter reuse.
AB  - The practice of single use devices (SUD) recycling raises public health concerns,
      primarily with regard to the potential risks of infection and device malfunction.
      These concerns have led to a Food and Drug Administration (FDA) revision of the
      present regulations. The purpose of our work is to identify different material
      parameters that could contribute to the health risks associated with the practice
      of reprocessing PVC catheters for use in other patients. Ethylene oxide hospital
      reprocessed central venous catheter samples were obtained from the stock of a
      health-care institution. One device trademark was selected, and samples that had
      been used 8 and 24 times were compared with new ones. In order to determine the
      total percentage of extractables, supercritical fluid extraction (SFE) was used,
      and off-line gas-chromatography-flame-ionization detection (GC-FID) was employed
      for identification and quantitation of bis-(2-ethyl hexil)phthalate (DEHP).
      Storage modulus (E') and dissipation factor (tan delta curves were obtained by
      dynamic mechanical analysis (DMA). Successive catheter recycles produced
      increased plasticizer loss, increased glass transition temperature (T(g)) and E',
      widening of tan delta curve with a simultaneous shift to higher temperature,
      small decrease of weight average molecular weight (M(w)), increased surface
      roughness, and increased appearance of surface grooves (severe damage). The
      magnitude of biomaterial parameter changes measured suggests that reuse could
      alter the original device performance. Examples of possible adverse clinical
      events include leaching of toxic agents, device rigidization or breakage,
      increased catheter protein retention, or the promotion of bacterial adhesion by
      device topography modification.

PMID- 11505425
TI  - The pH dependence of monofilament sutures on hydrolytic degradation.
AB  - Hydrolytic degradation of two nonabsorbable sutures, four absorbable sutures, and
      a new type of absorbable suture was studied in buffered media of various pHs at
      37 degrees C. The pH levels fixed in this study were 1.0, 7.4, 8.5, and 10.5.
      Physical measurements were made on the retention of tensile strength and melting
      temperature of the sutures after hydrolysis for 12 weeks. Sutures containing
      glycolic acid as a comonomer exhibited enhanced degradation in alkaline media,
      similar to polyglycolide multifilament sutures. Poly-p-dioxanone (PDS II) suture
      lost strength to a significant extent at pH 1.0, suggesting that care should be
      taken when this suture is used for closing tissues in contact with acidic media,
      such as the stomach. In marked contrast, the degradation of lactide-epsilon
      caprolactone copolymer [P(LA/CL)] suture was not sensitive to the pH of media.
      The surface morphology of hydrolyzed sutures varied, depending on the pH of
      media. Particularly, moon-crater-shaped impressions were observed on glycolide
      epsilon-caprolactone copolymer (MONOCRYL) and glycolide-trimethylene carbonate
      dioxanone copolymer (BIOSYN) sutures. Among the nonabsorbable sutures, nylon
      (ETHILON) exhibited the fastest loss of strength in acidic buffer solution, and
      polypropylene (PROLENE) suture retained most of its initial strength at all pHs
      studied.

PMID- 11505426
TI  - The apparent volume of interdigitation: a new parameter for evaluating the
      influence of surface topography on mechanical interlock.
AB  - A new parameter has been defined to estimate the apparent volume of
      interdigitation (V(i)) that is available from a surface to support mechanical
      interlock. The parameter is estimated in terms of the core roughness parameters,
      which can be obtained from the material ratio curve of a representative surface
      profile. A verification of the definition for V(i) is performed with the use of
      ideal surface profiles consisting of Gaussian and skewed height distributions. In
      contrast to conventional surface roughness parameters, the expression for V(i) is
      capable of differentiating between positive and negative skewed surfaces with the
      same average surface roughness. It is expected that V(i) will be a useful tool
      for optimization of the prosthesis and bone surface topographies, which are
      essential to the long-term success of cemented total joint replacements.

PMID- 11505427
TI  - Effects of filler composition and surface treatment on the characteristics of
      opaque resin composites.
AB  - The effects of filler composition and surface treatment of titanium dioxide
      (TiO2) on the shear bond strength to noble metal and mechanical properties of
      opaque dental resin composites were assessed. A series of fillers for resin
      composites were prepared with untreated TiO2 or treated silica/alumina-coated
      TiO2 with silane coupling agent; these fillers were replaced with silanized SiO2
      in increasing amounts. Each of various powder compositions were mixed with the
      liquid and applied to the surface of a silver-palladium-copper-gold (Ag-Pd-Cu-Au)
      alloy and light cured. A light-activated resin-veneering composite material was
      placed on top with the use of a brass ring mold and light cured. Specimens were
      stored at 37 degrees C in water for a period of 24 h. Additionally some specimens
      were thermocycled at 4 degrees C and 60 degrees C in water baths for 1 min each
      for 5000 cycles before shear mode testing was performed. Light-activated opaque
      resin composites containing filler with specific filler compositions of 50 wt% of
      untreated TiO2-50 wt% of silanized SiO2 (untreated TiO2(50)) and 40 wt% of
      untreated TiO2-60 wt% of silanized SiO2 (untreated TiO2(40)) showed higher shear
      bond strengths to the Ag-Pd-Cu-Au alloy than any other specific compositions when
      no thermocycling was involved. Surface treatment of TiO2 filler and TiO2(50)- and
      TiO2(40)-opaque resin composites prepared thereof showed significantly higher
      shear bond strengths than untreated TiO2(50)- and TiO2(40)-opaque resin
      composites when subjected to thermocycling. Surface-treated opaque resin
      composite had significantly higher compressive and flexural strength than
      untreated opaque resin composite after immersion in water for 1 month. Scanning
      electron microscopy of the fractured opaque resin composite surface showed an
      interface failure between TiO2 and the matrix resin for untreated composite, and
      cohesive failure within the resin for surface-treated composite. Surface-treated
      TiO2(50) and TiO2(40) may be clinically useful as the filler for light-activated
      opaque dental resin composites.

PMID- 11505428
TI  - Suppressive effects of interleukin-4 and interleukin-10 on the production of
      proinflammatory cytokines induced by titanium-alloy particles.
AB  - We investigated the effects of two anti-inflammatory cytokines, interleukin (IL)
      4 and IL-10, on the production of two proinflammatory cytokines, tumor necrosis
      factor (TNF)-alpha and IL-6, induced by titanium-alloy (Ti6Al4V) particles. Human
      monocytes isolated from the peripheral blood of six healthy donors were cultured
      and exposed to retrieved titanium-alloy particles, together with IL-4 or IL-10.
      Enzyme-linked immunosorbent assay and reverse transcription-polymerase chain
      reaction showed that both IL-4 and IL-10 significantly reduced the production of
      TNF-alpha and IL-6. The level of TNF-alpha decreased by 74% with IL-4 and 56%
      with IL-10. The level of IL-6 decreased by 55% with IL-4 and by 66% with IL-10.
      IL-4 had more consistent suppressive effect on TNF-alpha production. The results
      from this study provide in vitro evidence of the possible utility of IL-4 and IL
      10 in suppression of particle-induced activation of macrophages.

PMID- 11505429
TI  - Relating nickel-induced tissue inflammation to nickel release in vivo.
AB  - Nickel has a number of adverse biological effects that have made the use of
      nickel in biomedical implants controversial. Yet information about the
      distribution of nickel in tissues around nickel-containing implants is scarce.
      The purpose of the current study was to use a laser ablation technique, combined
      with inductively coupled mass spectroscopy, to assess the spatial distribution of
      nickel around nickel-containing implants in vivo. Polyethylene, pure nickel wire,
      or a nickel-containing alloy (Ni-Cr) were implanted subcutaneously into rats for
      7 days. The tissues were analyzed for Ni content and inflammation at 1-mm
      intervals up to 5 mm away from the implants. The sham surgery sites and the
      polyethylene caused mild to moderate inflammation 1-2 mm from the implant site
      with no detectable nickel in the tissue. The nickel wire caused severe
      inflammation up to 5 mm away from the implant site with necrosis for 1 mm around
      the implant. Nickel concentrations reached 48 microg/g near the implants, falling
      exponentially to undetectable levels at 3-4 mm from the implants. The Ni-Cr wire
      caused inflammation equivalent to polyethylene, with less than 4 microg/g of
      nickel present in the tissue for 1-2 mm around the implants. The current study
      showed that the laser-ablation technique was well suited for the analysis of soft
      tissues for metal-ion content, and that the nickel distribution in tissues
      correlated well with overt tissue inflammation.

PMID- 11505430
TI  - A tissue sealant based on reactive multifunctional polyethylene glycol.
AB  - A rapidly gelling synthetic tissue sealant was developed from tetra-succinimidyl
      and tetra-thiol-derivatized polyethylene glycol (PEG). The two reagents were
      dissolved in aqueous buffers at 20% (w/v) solids and sprayed on the tissue site,
      with the use of a sprayer/mixer device. Good adhesion to collagen membranes, PTFE
      grafts, and carotid artery was observed in vitro. In a burst test on collagen
      membranes with a 2-mm orifice defect, the gel sustained fluid pressures of 125 +/
      36 mm Hg (n = 18), fivefold greater than capillary blood pressure and one-half
      that observed in hypertension. On 0.4-mm-diameter puncture defects in PTFE
      grafts, pressures of 390-490 mm Hg were sustained, and on 0.6-0.9-mm puncture
      defects in carotid arteries, pressures of 490 to 840 mm Hg were sustained. In
      vitro data corresponded to results in vivo, where bleeding in rabbit arteries was
      stopped immediately in five out of six trials. A significant reduction in time to
      hemostasis and blood loss, compared to controls, was observed. Carotid artery and
      subcutaneous implant data in rabbits showed that the formula was compatible with
      biological tissue. Rapid gelling and effective sealing were dependent on the
      presence of active succinimidyl ester and thiol groups on PEG. HPLC and chemical
      substitution methods were useful in predicting whether batches of derivatized PEG
      would perform satisfactorily.

PMID- 11505431
TI  - Biofilm formation and design features of indwelling silicone rubber
      tracheoesophageal voice prostheses--an electron microscopical study.
AB  - After total laryngectomy, voice can be restored with a silicone rubber
      tracheoesophageal voice prosthesis. However, biofilm formation and subsequent
      deterioration of the silicone material of the prosthesis will limit device life
      by impairing valve function. To simulate the natural process of biofilm
      development under dynamic nutrient conditions, a modified Robbins device was used
      to evaluate the biofilm-related valve dysfunction of the Groningen, Provox2, Blom
      Singer indwelling, and VoiceMaster voice prostheses. Obstruction of the
      semicircular slit-valved Groningen prosthesis leading to increased airway
      resistance was caused not only by a buildup of deposits on the esophageal flange
      and valve hat, but also by accumulation of deposits on the semicircular valve
      seating. The hinged flap valved Provox2 and indwelling Blom-Singer prostheses
      failed to close sufficiently because of biofilm formation on the valve seating.
      The esophageal flange of the VoiceMaster prosthesis was affected, but the tripod
      structure of the ball valve was fully colonized up to the titanium sleeve, which
      interfered with proper valve opening and closure. These findings on biofilm
      formation could be used for the further development and modification of critical
      design features of voice prostheses to facilitate tracheoesophageal speech.

PMID- 11505432
TI  - A composite polymer/tricalcium phosphate membrane for guided bone regeneration in
      maxillofacial surgery.
AB  - The aim of the study was the development of a resorbable membrane for guided bone
      regeneration (GBR) with improved biocompatibility, which should be stiff enough
      to avoid membrane collapse during bone healing. Combining a bioactive ceramic
      with a resorbable polymer may improve the biocompatibility and osteoconductivity
      of resorbable devices. The present article describes the preparation, the
      mechanical properties, and the in vitro degradation characteristic of a composite
      membrane made of poly(L, DL-lactide) and alpha-tricalcium phosphate in comparison
      to a membrane made of pure poly(L, DL-lactide). The tensile strength and the
      elastic modulus as well as the molecular weight of the membranes were measured
      after in vitro degradation in buffer at 37 degrees C up to 28 weeks. The initial
      tensile strength of the composite and the polymer membrane was 37.3 +/- 2.4 MPa
      and 27.7 +/- 2.3 MPa and the elastic modulus 3106 +/- 108 MPa and 3101 +/- 104
      MPa, respectively. The mechanical properties remained constant up to 8 weeks and
      then decreased slowly until week 28. The molecular weight of both membranes
      decreased steadily from 170,000 D to 30,000 D. It was concluded that the
      mechanical requirements for a membrane for GBR were fulfilled by the composite
      membrane.

PMID- 11505433
TI  - Material fundamentals and clinical performance of plasma-sprayed hydroxyapatite
      coatings: a review.
AB  - The clinical use of plasma-sprayed hydroxyapatite (HA) coatings on metal implants
      has aroused as many controversies as interests over the last decade. Although
      faster and stronger fixation and more bone growth have been revealed, the
      performance of HA-coated implants has been doubted. This article will initially
      address the fundamentals of the material selection, design, and processing of the
      HA coating and show how the coating microstructure and properties can be a good
      predictor of the expected behavior in the body. Further discussion will clarify
      the major concerns with the clinical use of HA coatings and introduce a
      comprehensive review concerning the outcomes experienced with respect to clinical
      practice over the past 5 years. A reflection on the results indicates that HA
      coatings can promote earlier and stronger fixation but exhibit a durability that
      can be related to the coating quality. Specific relationships between coating
      quality and clinical performance are being established as characterization
      methods disclose more information about the coating.

PMID- 11505434
TI  - Wear of retrieved ceramic THA components--four matched pairs retrieved after 5-13
      years in service.
AB  - Retrieval analyses of alumina-alumina THA components are conducted in order to
      investigate in vivo wear of implants and provide guidance to material and design
      improvements. The contribution of the present study consists of the examination,
      by digital recording of spherical profiles and scanning electron microscopy, of
      four matched pairs of ceramic THA implants retrieved after 5, 11, 13, and 13
      years in service because of mechanical loosening. Maximum wear depth values on
      measured surfaces ranged between 10-325 microm for heads and 25-784 microm for
      cups, while grossly worn areas varied between 240 and 1510 mm(2) for heads and
      250 and 1570 mm(2) for cups. The greatest wear characteristics were demonstrated
      by the pair that served for 5 years, that is, on the cup that was found in a 65
      degrees inclination. Quantitative topographical study of the results provided
      concrete evidence of a cascade of detrimental wear events of changing geometry,
      intensity, and progression associated with gradual cup tilting. Microscopy
      findings support previously recognized wear mechanisms.

PMID- 11505435
TI  - Time-dependent mechanical properties of HA/TCP particles in relation to
      morsellized bone grafts for use in impaction grafting.
AB  - In reconstructive surgery human bone defects are sometimes filled with the use of
      the impaction bone grafting technique. Currently different types of biomaterial
      particles are being developed as bone-substitute materials. Before these
      biomaterials can be applied their mechanical and biological behavior should be
      characterized. In this study the time-dependent mechanical behavior of
      biomaterial particles with different tri-calcium-phosphate/hydroxy-apatite
      (TCP:HA) ratios, particle sizes, and porosities is determined and compared to the
      behavior of human bone grafts, the latter being the standard material currently
      used to augment bone defects. The mechanical properties were assessed with the
      use of dynamic confined compression creep tests with a loading and unloading
      phase. Different graft material groups were tested, consisting of 100% human bone
      grafts, 100% biomaterial particles, and 50:50 weight mixtures of human grafts and
      biomaterial particles. No damage to the particles was observed by the impaction
      in the test chamber or by the dynamic load. Relative to the human graft material,
      the biomaterial particles hardly deformed under loading, were much stiffer, and
      showed almost no viscoelastic behavior. The mixtures showed intermediate results.
      Particle size and porosity influenced the behavior of the biomaterial particles.
      TCP:HA ratio did not have a great effect. The conclusion is that the application
      of these particles should be done with great care, as their mechanical behavior
      is drastically different than that of the human graft material. Mixing it with
      human bone grafts gave the material some biphasic, viscoelastic behavior that may
      be important for its biological response.

PMID- 11505436
TI  - Serological and molecular screening for viruses in blood donors from Ntcheu,
      Malawi: high prevalence of HIV-1 subtype C and of markers of hepatitis B and C
      viruses.
AB  - The prevalence of antibodies to human immunodeficiency virus type 1 (HIV-1),
      hepatitis C virus (HCV), human T lymphotropic virus I (HTLV-I), and hepatitis B
      (HBV) surface antigen (HBsAg) was determined in blood donors from Ntcheu, Malawi.
      Each donation was also screened for HIV-1 RNA and HCV RNA. Among 159 blood
      donations, the prevalence of HIV-1 infection was 10.7%, 8.1% for HBV carriage,
      6.8% for anti-HCV, and 2.5% for anti-HTLV-I. HIV-1/HTLV-I and HIV-1/HCV dual
      infections were observed in 1.2% of the donations. Consequently, 13% of blood
      donors from Ntcheu should be deferred for retroviral infections and 15% for
      hepatitis viral infections. Sequence analyses of the HIV-1 strains revealed a
      relatively homogeneous circulation of subtype C viruses in Malawi. These findings
      confirm the high endemicity of blood-borne viruses in Malawi and the need for a
      sensitive viral screening of blood donations to improve blood safety.

PMID- 11505437
TI  - Long-term persistence of antibodies induced by vaccination and safety follow-up,
      with the first combined vaccine against hepatitis A and B in children and adults.
AB  - It is important to monitor the long-term persistence of antibodies induced by
      vaccination. Four cohorts were followed for their long-term immunity after
      vaccination with a combined hepatitis A and B vaccine (Twinrix; SmithKline
      Beecham Biologicals, Rixsenart, Belgium). Two cohorts of adults (ages 17-60
      years), one of 1-6-year-olds, and one of 6-15-year-olds were vaccinated following
      a 0, 1, and 6-month schedule. Follow-up data until month 72 (adults) and month 60
      (children) are available. At month 72, antibody to hepatitis A virus (anti-HAV)
      seropositivity (S+) was 100% for both adult cohorts (n = 40 and n = 47) and 95%
      and 89% of the vaccinees were seroprotected against hepatitis B virus (HBV),
      respectively. The geometric mean titres (GMTs; mIU/ml) for anti-HAV were 977 and
      542 and the GMTs for the antibody to hepatitis B surface antigen (anti-HBs) were
      322 and 90. For 1-6-year-olds at month 60 (n = 39), anti-HAV S+ was 100% with a
      GMT of 479 and 97% were protected against HBV with a GMT of 195. At month 60 for
      the 6-15-year-olds (n = 42), anti-HAV S+ was 100% with a GMT of 990 and 95% were
      protected against HBV with a GMT of 263. There have been no safety issues during
      the follow-up. In the past 5 years, a postmarketing surveillance system was
      available. Using this system, all spontaneous adverse events are collected and
      archived. Although infrequent, the most commonly reported adverse events after
      more than 13 million doses were allergic-type reactions followed by fever and
      injection site reactions. The combined hepatitis A and B vaccine is safe and is
      well tolerated. Immunity provided by the vaccine remains high in adults and
      children with comparable results to those obtained with monovalent vaccines.

PMID- 11505438
TI  - Study of the infection of human blood derived monocyte/macrophages with hepatitis
      C virus in vitro.
AB  - Hepatitis C virus (HCV) is essentially hepatotropic, but clinical observations
      based on quasispecies composition in different compartments or on viral RNA
      detection in cells suggest that the virus is able to infect and persist in cells
      other than liver cells. It was shown previously that peripheral blood mononuclear
      cells (PBMCs) are permissive to HCV replication in vitro but at a very low rate.
      Since different viruses associated with chronic infections are known to persist
      in monocyte/macrophages, it is important to determine whether these mononuclear
      blood cells are susceptible preferentially to HCV. In order to study HCV
      interaction with monocytes/macrophages, these cells were isolated from the blood
      of healthy donors and incubated with HCV genotype 1b positive sera. The detection
      by RT-PCR of the positive- and negative-strand RNA in the cells at different
      times and the increase in the amount of intracellular viral RNA measured by the
      branched DNA assay suggest that monocyte/macrophages can support HCV RNA
      replication. The rate, however, is very low. The analysis of hypervariable region
      1 (HVR-1) nucleotide sequences indicated that some minor variant present in the
      inoculum might display a specific tropism for the monocytes/macrophages. These
      results provide evidence that human monocytes/macrophages might represent a
      reservoir for HCV. This cell tropism may be a crucial factor in the pathogenesis
      of hepatitis C.

PMID- 11505439
TI  - Cross-reactivity and clinical impact of the antibody response to hepatitis C
      virus second envelope glycoprotein (E2).
AB  - The genotype of hepatitis C virus (HCV) can profoundly affect the success of
      antiviral therapy for HCV infection. A possible contributing factor is a varied
      immune response elicited by infection with different HCV genotypes. In this
      study, full-length E2 proteins of HCV genotypes 1a, 1b, 2a, and 2b were used to
      determine the fraction of the humoral immune response to HCV E2 that is genotype
      specific. Greater than 90% of all infected individuals had serum antibodies to
      the four E2 proteins. Overall, individuals infected with genotype 1a or 1b were
      characterized by variable immune responses to HCV E2 with relatively high amounts
      of cross-reactivity with other E2 proteins. Individuals infected with genotype 2a
      or 2b exhibited a strong preferential reactivity to genotype 2a and 2b E2
      proteins. Individuals with elevated titers to HCV E2 were more likely to be
      infected with genotype 2a and had a significantly lower median viral load. These
      findings indicate that the antibody response to HCV E2 is affected by the
      genotype of the virus and that induction of a strong humoral immune response to
      HCV E2 may contribute to a decreased viral load.

PMID- 11505440
TI  - Persistent hyperendemicity of hepatitis C virus infection in Taiwan: the
      important role of iatrogenic risk factors.
AB  - The purpose of this study was to investigate determinants of endemic hepatitis C
      virus (HCV) infection within communities in Taiwan. A two-phase study, including
      a seroprevalence survey and a prevalent case-control study at the first phase,
      which has been published previously, and a follow-up seroconversion determination
      and an incident case-control study during the second phase, was carried out to
      evaluate correlates of persistent endemic HCV infection. At the first phase, a
      total of 12,021 men and 1,819 women who were 30-64 years old and living in seven
      townships in Taiwan were tested for the seroprevalence of antibodies to HCV (anti
      HCV). In addition, a prevalent case-control study involving 272 HCV-positive
      cases and 282 seronegative controls identified from the anti-HCV testing was
      conducted to investigate risk factors associated with HCV prevalence. During the
      second phase, a total of 2,728 men and 834 women who were seronegative at
      recruitment participated in the 1-year prospective study on anti-HCV
      seroconversion. Subsequently, an incident case-control study based on 39
      seroconverters and 81 persistently seronegative controls were carried out to
      elucidate determinants of HCV seroconvertion. Antibodies to HCV were tested by
      the second-generation enzyme immunoassay. Information on risk factors of HCV
      infection was collected from subject interviews. The prevalence of anti-HCV
      consistently increased with age (range 2.9-5.4%), whereas no apparent age trend
      was observed for anti-HCV seroconversion rate (range 0.9-1.7%). A striking
      geographical variation in seroprevalence and seroconversion rates of anti-HCV was
      observed in the study townships. Furthermore, a significant geographical
      correlation between HCV seroprevalence and seroconversion rates was noted (r =
      0.962, P = 0.001). From the results of both prevalent and incident case-control
      comparisons, medical injections were found to be the main mode to sustain the
      persistent endemic state of HCV infection within a community (odds ratios for
      prevalent and incident case-control studies were 2.5 (95% CI = 1.7-3.6) and 3.1
      (95% CI = 1.4-7.1), respectively. The data indicate that the basis for HCV
      transmission has already been existed in study areas and the iatrogenic risk
      factor tended to be the major determinant for sustaining persistent endemicity
      within a community.

PMID- 11505441
TI  - Influence of the genetic heterogeneity of the ISDR and PePHD regions of hepatitis
      C virus on the response to interferon therapy in chronic hepatitis C.
AB  - Two genomic regions of hepatitis C virus (HCV), the interferon sensitivity
      determining region (ISDR) of the non-structural 5A gene (NS5A) and the protein
      kinase-RNA activated (PKR)-eukariotic transcription factor (eIF2-alpha)
      phosphorylation homology domain (PePHD) of the structural E2 gene, interact in
      vitro with the interferon-inducible cellular PKR protein kinase. Mutations within
      these regions might, therefore, influence the response to interferon therapy.
      Viral load at baseline and sequence heterogeneity of HCV in NS5A and E2 regions
      was studied in 74 HCV-1b and in 12 HCV-3a infected patients with chronic
      hepatitis C who were treated with interferon. As previously reported by us, in a
      smaller series of patients in which the ISDR region was analyzed [Saiz et al.
      (1998) Journal Infectious Diseases 177:839-847], in the present study a low viral
      load and a high number of amino acid mutations within the ISDR, but not within
      the PePHD region, were significantly associated with long-term response to
      interferon among HCV-1b infected patients. No relationship between these viral
      features and response to therapy was disclosed in patients infected with HCV-3a.

PMID- 11505442
TI  - Japan-specific subtype of hepatitis C virus genotype 1b, J subtype, has
      relatively low pathogenicity.
AB  - The prognostic implication of viral genotype 1b for hepatitis C virus (HCV)
      infection has been controversial, possibly due to the pathogenetic heterogeneity
      of genotype 1b. We analyzed two newly delineated subtypes of HCV genotype 1b
      subtypes with respect to progression of liver disease. Patients with chronic HCV
      1b infection (113 total, including 18 with chronic persistent hepatitis, 60 with
      chronic active hepatitis, 19 with cirrhosis, and 16 with hepatocellular carcinoma
      with cirrhosis) were studied to elucidate the factors associated with progression
      of liver disease. Factors evaluated included sex, age at diagnosis, blood
      transfusion history, and HCV genotype 1b subtype (W subtype or J subtype). W
      subtype was identified more often in association with chronic active hepatitis
      than with chronic persistent hepatitis (P = 0.0089), and more often in patients
      with cirrhosis than in those without (P = 0.0044). The age-, sex-, and
      transfusion history-adjusted odds ratios with respect to histological activity
      and presence of cirrhosis for W subtype compared to J subtype were 6.966 (1.856
      to 26.145) and 6.397 (1.506 to 27.179), respectively. Age at diagnosis was the
      most important risk factor for predicting development of cirrhosis and carcinoma.
      In conclusion, the W subtype of HCV 1b is associated closely with histologically
      active disease and development of cirrhosis, whereas the Japan-specific J subtype
      has relatively low pathogenicity. HCV genotype 1b, therefore, is heterogeneous in
      its pathogenicity.

PMID- 11505443
TI  - Cryoglobulinemia in Japanese patients with chronic hepatitis C virus infection:
      host genetic and virological study.
AB  - Essential cryoglobulinemia is associated closely with hepatitis C virus (HCV)
      infection. The mechanism responsible for occurrence of the disease is unclear.
      The aim of this study was to investigate pathogenetic roles of HCV in
      cryoglobulinemia. One hundred sixty-seven consecutive patients with HCV were
      studied clinically by HCV grouping, HCV RNA levels, GBV-C/HGV, HCV quasispecies
      (target region was hypervariable region-1) and HLA polymorphism. The quasispecies
      in cryoprecipitate were compared with those in supernatant. The results of HLA
      polymorphism of patients with cryoglobulinemia were compared with those without
      cryoglobulinemia and healthy controls. The frequency of HCV-related
      cryoglobulinemia was 71 of 167 (42.5%). Patients with cirrhosis (36 of 63, 57.1%)
      had cryoglobulinemia more frequently than those with chronic hepatitis (35 of
      104, 33.7%, P < 0.01). No significant differences were not found between the two
      groups (patients with and without cryoglobulinemia) in age, gender, HCV grouping,
      HCV RNA level and frequency of GBV-C/HGV. HCV was found quantitatively and
      clonally more frequently in the cryoprecipitate than in the supernatant. HLA
      polymorphism presented no significant differences among three groups. The stage
      of liver disease is one of pathogenetic factors. The greater the presence of HCV
      quasispecies in cryoprecipitate than in the supernatant indicates that various
      antigen presentations play an important role in the formation of cryoglobulin,
      whereas HLA typing dose not seem to contribute to the development of
      cryoglobulinemia.

PMID- 11505445
TI  - Fatal adenovirus type 7b infection in a child with Smith-Lemli-Opitz syndrome.
AB  - Adenovirus type 7 causes worldwide respiratory tract infections, mainly in
      children. Severe systemic infections can occur, especially in immunocompromised
      patients and in patients with underlying chronic diseases. This report describes
      the first case of a fatal disseminated adenovirus type 7 infection in a child
      with Smith-Lemli-Opitz syndrome, a rare autosomal recessive disorder due to a
      primary enzymatic defect in cholesterol metabolism. Nasopharyngeal secretions and
      autopsy specimens including liver, lung, pleural fluid, and rectum were collected
      for viral culture. Adenovirus serotype 7 strains were obtained from all anatomic
      sites, except the liver. All these clinical isolates were analyzed using
      restriction endonuclease digestion of the genome, identifying them as genome type
      7b, a virulent type. In this case, the fatal evolution could have been
      accelerated by the presence of an immunodeficiency although immunodeficiency is
      not included in the definition of Smith-Lemli-Opitz syndrome. The frequent
      recurrent banal infections in Smith-Lemli-Opitz syndrome could be prevented by a
      cholesterol supplementation regimen. Finally, this report emphasizes the need for
      efficient therapy for disseminated adenovirus infections, especially for virulent
      genome types.

PMID- 11505444
TI  - Changing prevalence of hepatitis C virus genotypes: molecular epidemiology and
      clinical implications in the hepatitis C virus hyperendemic areas and a tertiary
      referral center in Taiwan.
AB  - To determine the hepatitis C virus (HCV) genotype distribution in Taiwan and to
      clarify the relationship between genotype and the pathogenesis of HCV infection,
      1,164 subjects positive for serum HCV antibodies and HCV RNA from three HCV
      hyperendemic areas (Masago, Tzukuan, and Taoyuan) and a tertiary referral center
      in Taiwan were studied during 1995-1997. HCV genotypes and viral loads were
      determined using Okamoto's method and branched DNA assay, respectively. Genotype
      1b was the most prevalent in Tzukuan (61.9%), Taoyuan (76.9%), and the referral
      center (47.0%). By contrast, genotype 2a was the major HCV type in Masago
      (63.5%). Prevalence of genotype 1b positively and that of genotype 2a negatively
      correlated to age, regardless of study populations (P < 0.01). Based on
      multivariate analysis, the significant factors associated with the presence of
      cirrhosis, with or without hepatocellular carcinoma, in chronic hepatitis C
      patients were genotype 1b and age. In conclusion, these results underline that
      independent HCV outbreaks continue in HCV hyperendemic areas in Taiwan,
      concomitant with a changing relative prevalence of HCV genotypes in relation to
      age. Both the correlation of genotype 1b with age (cohort effect) and intrinsic
      properties of HCV genotypes are probably responsible for the association between
      genotype and the pathogenesis of HCV infection.

PMID- 11505446
TI  - Aciclovir selects for ganciclovir-cross-resistance of human cytomegalovirus in
      vitro that is only in part explained by known mutations in the UL97 protein.
AB  - Phenotypically, ganciclovir-resistant human cytomegalovirus strains could be
      selected by aciclovir as effectively as by ganciclovir in vitro. Three clinical
      human cytomegalovirus isolates with different sensitivities against ganciclovir,
      aciclovir, foscarnet, and cidofovir, but without any mutation in the viral UL97
      protein known to confer ganciclovir resistance, were propagated each in duplicate
      in the presence of ganciclovir or aciclovir. After drug selection, all 12 strains
      were less susceptible to ganciclovir (increase of 50% focus reduction dose
      between 2.1- and 31.5-fold) but were still sensitive to foscarnet and cidofovir;
      7/12 exhibited a ganciclovir-resistant phenotype with a 50% focus reduction dose
      >30 microM, and in 6 out of these typical mutations in the UL97 coding region
      could be found by genotyping. All four strains selected from one isolate carried
      the identical UL97 mutation at amino acid position 460 (methionine to valine).
      The decreased sensitivity to ganciclovir and aciclovir in the other strains could
      neither be attributed to known UL97 mutations nor to mutations in the viral
      polymerase (UL54), which have been reported to induce resistance.

PMID- 11505447
TI  - Lack of association between the kinetics of human cytomegalovirus (HCMV)
      glycoprotein B (gB)-specific and neutralizing serum antibodies and development or
      recovery from HCMV active infection in patients undergoing allogeneic stem cell
      transplant.
AB  - The kinetics of the gB-specific and neutralizing antibody responses to human
      cytomegalovirus (HCMV) were analyzed in 26 allogeneic stem-cell transplant
      recipients who either did (n = 20) or did not (n = 6) develop asymptomatic HCMV
      active infection during the study period. Antibody response profiles varied
      widely among individuals in both groups, irrespective of whether HCMV active
      infection did or did not occur. Development of HCMV active infection was not
      preceded by a decline in functional serum antibody levels. Neither the absence
      nor the presence of HCMV active infection correlated with either high or low
      serum levels of gB-specific and neutralizing antibodies, respectively. In most
      patients, episodes of HCMV replication were not followed by a marked increment in
      functional serum antibody titers. Therefore, resolution of an ongoing HCMV active
      infection was not associated with a vigorous antibody response to viral
      replication. In addition, this study supports previous data indicating that
      passive transfer of human immunoglobulins may result in an increment in gB
      specific and neutralizing serum antibody levels, the magnitude of which varies
      among recipients; however, both patients with and without measurable increments
      in serum antibody levels developed HCMV active infections with comparable
      frequency.

PMID- 11505448
TI  - Area under the viraemia curve versus absolute viral load: utility for predicting
      symptomatic cytomegalovirus infections in kidney transplant patients.
AB  - A novel approach to predicting symptomatic cytomegalovirus (CMV) infections
      combines the level and the duration of viraemia in a single parameter. Sixty-four
      kidney transplant recipients were monitored by quantitative shell vial culture,
      pp65 antigenaemia, and polymerase chain reaction (PCR) of leucocytes. The area
      under the curve (AUC) of each parameter was determined from the onset of viraemia
      to the beginning of antiviral treatment. The AUC values were significantly higher
      in symptomatic than in asymptomatic patients. For antigenaemia and PCR, optimal
      AUC thresholds for predicting symptomatic CMV infections were determined. They
      were superior to standard cutoff levels of absolute viral load in sensitivity,
      specificity, and positive and negative predictive value. In 8 of the 23 patients
      who became symptomatic, impending clinical features were indicated earlier by the
      AUC thresholds than by standard viral load. In conclusion, the concept of the AUC
      should facilitate identification of patients at risk of symptomatic CMV
      infection.

PMID- 11505449
TI  - Human cytomegalovirus a sequence and UL144 variability in strains from infected
      children.
AB  - Human cytomegalovirus (HCMV) displays genetic polymorphisms. This variability may
      contribute to strain-specific tissue tropism and disease expression in HCMV
      infected humans. To determine strain variability in a sequence and UL144 gene
      regions, 51 low-passage isolates from 44 HCMV-infected children were studied.
      Isolates were obtained from 28 healthy children attending child care centers in
      Iowa and from 16 congenitally infected infants born in Texas. Isolates
      demonstrated substantial nucleotide variation in each gene region. Phylogenetic
      analysis of a sequence variability allowed 39 isolates to be grouped into six
      clades. The largest clade contained 16 isolates with > or = 95% nucleotide
      homology. Forty-eight of the 49 HCMV isolates yielding UL144 amplicons was
      grouped according to the clades described a few years ago [Lurain et al. (1999)
      Journal of Virology 73:10040-10050]. No linkage was observed among a sequence,
      UL144, and glycoprotein B (gB; UL55) polymorphisms. Four Texas and 11 Iowa
      isolates displayed > or = 95% sequence homology for a sequence and UL144 regions
      and possessed identical gB genotypes. No relationship between UL144 polymorphisms
      and outcome of congenital HCMV infection was observed. These data indicate that
      HCMV strains circulating among young children have UL144 polymorphisms similar to
      those of HCMV strains excreted by immunocompromised adults. Identification of
      conserved nucleotide sequences among Iowa and Texas children suggests genetic
      stability and biologic importance of these gene regions.

PMID- 11505450
TI  - Plasma concentrations of sVCAM-1 and severity of dengue infections.
AB  - Adhesion molecules are essential for the immune response. They are involved in
      the regulation of cell-to-cell contact, thereby enabling leukocytes to
      communicate. Circulating forms of adhesion molecules are found in the serum of
      healthy individuals. Raised levels have been associated with disease severity in
      HCV and other infections and thus appear to be good markers of endothelial
      damage. The levels of soluble Vascular Cell Adhesion Molecule-1 (sVCAM-1) and of
      sP and sL-selectin in the plasma of children hospitalised for dengue in French
      Polynesia were monitored. Studies from the 1996/1997 dengue-2 outbreak, showed
      that levels of sVCAM-1 increase steadily during the febrile period, peak on day
      7, and then decline relatively rapidly. Disregarding the time frame within the
      febrile period, sVCAM-1 levels were always higher compared to controls. There was
      a significant association between sVCAM-1 levels and dengue haemorrhagic fever, a
      severe manifestation of dengue virus infection characterised by plasma leakage.
      No association was apparent between sVCAM-1 levels and primary vs. secondary
      dengue virus infections. Levels of sP-selectin and sL-selectin were significantly
      higher in primary compared with secondary infection but were not different in
      patients presenting with plasma leakage. Lastly, sVCAM-1 levels were
      significantly higher in an outbreak of severe disease in 1989/1990 (dengue-3)
      when compared to a non-severe outbreak in 1988/1989 (dengue-1) and a mild
      outbreak in 1996/1997 (dengue-2). The results suggested that levels of sVCAM-1
      production might prove to be a useful marker in the management of severe dengue.

PMID- 11505451
TI  - Comparative analysis of the expression of the Epstein-Barr virus (EBV) anti
      apoptotic gene BHRF1 in nasopharyngeal carcinoma and EBV-related lymphoid
      diseases.
AB  - Epstein-Barr virus (EBV) has been identified in a wide range of neoplastic and
      non-neoplastic disorders. The EBV open reading frame BHRF1 encodes a protein with
      partial sequence and functional homology to the anti-apoptotic onco-protein Bcl-2
      and may therefore have a role in the proliferation of EBV positive cells. We have
      developed a rat monoclonal antibody against pBHRF1, which can detect BHRF1 in
      paraffin sections. While a number of mutant versions of BHRF1 were recognised,
      the monoclonal did not detect the BHRF1 homologue encoded by Herpesvirus papio or
      two mutants with deletions in the BH2 region. This novel rat monoclonal antibody
      (6A9) was used to examine tissue sections from 39 cases of non-keratinising
      undifferentiated nasopharyngeal carcinoma (NPC), 6 cases of metastatic NPC, 7
      cases of EBV-positive NPC with squamous differentiation from Chinese patients, 15
      cases of EBV-positive post-transplant lymphoproliferative disorder (PTLD), 6 EBV
      containing lymphoblastoid cell lines, and 2 cases of oral hairy leukoplakia
      (OHL). In 11 cases of undifferentiated NPC, RT-PCR data were available for
      comparison with the immunohistochemistry. Both cases of OHL and two cases of LCL
      were positive for BHRF1 but none of the PTLD showed positive staining. All cases
      of undifferentiated NPC were positive for Bcl-2 but only one BHRF1 positive cell
      was identified in 1 of 39 cases of primary undifferentiated NPC. The 6A9 antibody
      produced less background staining and no nuclear positivity compared with the
      commercially available mouse monoclonal 5B11. It is concluded that BHRF1 can not
      be detected by immunohistochemistry in NPC and therefore it appears not to play a
      significant anti-apoptotic role in the progression of this EBV-associated tumour.
      The 6A9 monoclonal appears to be superior to 5B11 for the detection of pBHRF1 in
      tissue sections.

PMID- 11505452
TI  - Expression of the simian Epstein-Barr virus-encoded latent membrane protein-1 in
      malignant lymphomas of SIV-infected rhesus macaques.
AB  - During the course of simian immunodeficiency virus (SIV) infection, nearly 15% of
      rhesus macaques (Macaca mulatta) and up to 40% of cynomolgus macaques (Macaca
      fascicularis) developed SIV-associated non-Hodgkin's lymphomas. Most of these
      malignant lymphomas harbored lymphocryptoviruses, which are closely related to
      the human Epstein-Barr virus (EBV; Herpesvirus M. mulatta and Herpesvirus M.
      fascicularis). To characterize the oncogenic role of simian EBV infection for
      lymphomagenesis during SIV infection, expression of the EBV-encoded latent
      membrane protein-1 (LMP-1) was analyzed in malignant lymphomas of SIV-infected
      rhesus macaques. Nine seropositive rhesus macaques suffering from B-cell
      lymphomas during the late phase of SIV infection were euthanized. Latency stages
      of EBV infection within malignant lymphomas and simian EBV-infected
      lymphoblastoid cell lines (LCL8664, H50) were characterized by analyzing
      expression of the EBV-encoded nuclear antigens EBNA-1, EBNA-2, and small RNAs
      EBER1/2. In parallel, the presence of viral LMP-1 transcripts was assessed by
      reverse transcription-polymerase chain reaction (RT-PCR) and in situ
      hybridization. Results were compared with findings in AIDS-associated malignant
      lymphomas in two patients infected with human immunodeficiency virus (HIV)-1.
      Rhesus macaques developed high-grade B-cell lymphomas of the centroblastic (five
      of nine), immunoblastic (two of nine), centroblastic-centrocytic (one of nine),
      and Burkitt-like (one of nine) subtypes within 18-29 months postinfection with
      SIV(mac)251/32H. The presence of Herpesvirus M. mulatta was detected in eight of
      nine cases. Transcription of the viral oncogene LMP-1 could be demonstrated
      within the simian EBV-infected cell lines as well as in four of nine SIV
      associated malignant lymphomas. These four cases and both of the HIV-1-related
      non-Hodgkin's lymphomas expressed the full spectrum of latent EBV gene products
      (LMP-1, EBER1/2, EBNA-1, EBNA-2) and were thus classified as latency type III
      stages of EBV infection. Simian EBV infection was demonstrated in 90% of
      lymphomas in SIV-infected rhesus macaques. Analysis of LMP-1 expression suggests
      an important role for this viral oncogene in the pathogenesis of both SIV and HIV
      1-associated malignant lymphomas.

PMID- 11505453
TI  - Group 5: GBV-C/HGV isolates from South Africa.

PMID- 11505454
TI  - Kaposi's sarcoma-associated herpesvirus serology in Europe and Uganda:
      multicentre study with multiple and novel assays.
AB  - A multicentre study was undertaken to define novel assays with increased inter
      assay concordance, sensitivity, specificity and predictive value for serological
      diagnosis of human herpesvirus type 8 (HHV-8) infection. A total of 562 sera from
      European and Ugandan human immunodeficiency virus (HIV)-infected or uninfected
      individuals with or without Kaposi's sarcoma (KS) and blood donors were examined
      under code by 18 different assays in seven European laboratories. Sera from KS
      patients and all non-KS sera found positive by at least 70%, 80%, or 90% of the
      assays were considered "true positive." The validity of the assays was then
      evaluated by univariate logistic regression analysis. Two immunofluorescence
      assays (IFA) for detection of antibodies against HHV-8 lytic (Rlyt) or latent
      (LLANA) antigens and two enzyme-linked-immunosorbent assays (ELISA) (M2, EK8.1)
      for detection of antibodies against HHV-8 structural proteins were found to be
      highly concordant, specific, and sensitive, with odds ratios that indicated a
      high predictive value. When used together, the two IFA (Rlyt-LLANA) showed the
      best combination of sensitivity (89.1%) and specificity (94.9%). The performance
      of these assays indicate that they may be used for the clinical management of
      individuals at risk of developing HHV-8 associated tumours such as allograft
      recipients.

PMID- 11505455
TI  - Case of fatal encephalitis by HHV-6 variant A.
AB  - A fatal case is reported of encephalitis in an 85-year-old man caused by the
      human herpesvirus 6 variant A. The virological diagnosis was based on the
      findings of the virus variant genomic sequences both in the cerebrospinal fluid
      and serum of the patient. Moreover, virus replication in nervous tissue was
      suggested by a viral load higher in the cerebrospinal fluid than in the
      peripheral blood. The association of a central nervous system infection with the
      A variant of human herpesvirus 6 is interesting because of the difficulty in
      establishing a pathological role for this virus strain. Epstein-Barr virus DNA
      was detected in the patient's cerebrospinal fluid in association with human
      herpesvirus 6 DNA. The presence of the Epstein-Barr virus genomic sequences in
      the cerebro-spinal fluid was considered to be unimportant clinically.

PMID- 11505456
TI  - Molecular characterization of human enteroviruses in clinical samples: comparison
      between VP2, VP1, and RNA polymerase regions using RT nested PCR assays and
      direct sequencing of products.
AB  - Three nested RT-PCR assays were developed to permit sensitive typing of
      enteroviruses directly from clinical samples. These assays amplified short
      fragments from different genomic regions codifying for three proteins: VP2, VP1,
      and RNA polymerase. Given that enteroviruses have a high rate of degeneration
      within target codons among serotypes, the primers used consisted of mixed base
      and deoxyinosine residues. These techniques detected at 0.03-0.003 TCID50 of
      prototype Poliovirus 1 and Echovirus 30. They were used to characterize the
      enteroviral RNA detected in 18 CSF, stool, and throw swab samples and in 8
      enterovirus isolates from patients with several syndromes. Phylogenetic analysis
      in each independent sequenced region grouped the enterovirus into four clusters,
      enabling genetic classification. A comparative study was performed among the 26
      sequences obtained after direct sequencing of products with those available in
      the nucleotide databases. The efficiency of each assay for enterovirus
      identification was evaluated by both distance (Clustal) and similarity (M-NW)
      indices. Comparative results obtained independently in the three regions showed
      the highest yield of correlation between nucleotide sequences of all prototype
      serotypes and the analyzed genotypes in the VP1 region (26/26, 100% Clustal;
      22/26, 85% M-NW). Conversely, the VP2 region failed to identify some of the
      circulating enteroviruses (17/26, 65% Clustal; 16/26, 62% M-NW). Using the RNA
      polymerase region, sequences from samples and isolates were associated with
      prototype strains whenever these were available (20/21, 95% Clustal; 12/21, 57% M
      NW). These assays were useful for molecular identification of enterovirus
      directly from samples even when isolation was not possible.

PMID- 11505457
TI  - Oral antibodies to human papillomavirus type 16 in women with cervical neoplasia.
AB  - This study investigated the relationship between human papillomavirus type 16
      (HPV-16) antibodies detected in oral fluid from women with cervical neoplasia,
      their HPV-16 antibody seroprevalence, and their cervical HPV-16 DNA presence.
      Cervical HPV-16 DNA was detected by polymerase chain reaction in 43.2% (35/81) of
      these women. The prevalence of IgG and IgA antibodies to HPV-16 virus-like
      particles (VLP-16) in oral fluid and was investigated by enzyme-linked
      immunosorbent assay. Anti-VLP-16 IgA antibodies were detected in oral fluid from
      54.3% (44/81) of women with cervical neoplasia, compared with 8% (3/36) in
      controls (P = 0.000002). Anti-VLP-16 IgG was detected in oral fluid from 43.2.9%
      (25/72) and 13.3% (4/30; P = 0.029), respectively. Women who were HPV-16 DNA
      positive at their cervical lesion, displayed an oral fluid anti-VLP-16 IgA
      prevalence of 60.7% (17/28) and HPV-16 DNA negative women an oral fluid anti-VLP
      16 IgA prevalence of 50% (20/40; P = 0.38). Oral fluid anti-VLP-16 IgG prevalence
      in HPV-16 DNA positive women was 28.6% (8/28) compared with 40% (16/40) in oral
      fluid from HPV-16 DNA negative women (P = 0.3). Amongst HPV-16 DNA positive
      women, the anti-VLP-16 IgG seroprevalence was 75% (21/28) and IgA seroprevalence
      35.7% (10/28) and for the HPV-16 DNA negative women these values were 60% (24/40)
      and 32.5% (13/40), respectively. Oral IgA antibody testing proved no more
      sensitive than serum antibody detection for the determination of HPV infection
      but could be useful as a non-invasive screening method for women with cervical
      neoplasia and for estimating the mucosal antibody response to HPV vaccines.

PMID- 11505458
TI  - Detection of high-risk HPV types by the hybrid capture 2 test.
AB  - A hybrid capture test that can be used to detect at least 13 high-risk HPV types
      (referred to collectively as HPV-HR) in cervical scrapes (Hybrid Capture 2 probe
      set B, HC2-B) was evaluated. The HC2-B test is accurate and highly reproducible
      and the results obtained show excellent agreement with those obtained by a
      multiplexed type-specific polymerase chain reaction (mts-PCR). An additional
      assay to identify a subset of HPV-HR types may improve specificity without
      compromising sensitivity in HC2-B positive specimens with a test result close to
      the cut-off value given by 1 pg/ml HPV DNA.

PMID- 11505459
TI  - Detection of influenza a subtypes in community-based surveillance.
AB  - A rapid microtitre cell enzyme immuno assay (cell-EIA) was developed for the
      detection of influenza A subtypes in nasopharyngeal(NPS) swabs taken for
      surveillance. During the 1997/1998 influenza season in the United Kingdom, cell
      EIA was compared to cell culture for the detection and typing of influenza A
      viruses in NPS obtained by sentinel general practitioners in community
      surveillance. The cell EIA can also be used to detect different influenza A
      subtypes (H3N2, H1N1, H5N3, H5N1, H7N7, and H9N2) and was used as a rapid
      detection assay for the screening of individuals returning from Hong Kong with
      influenza-like illness suspected to be due to H5N1 in 1997/98, providing a rapid,
      efficient, inexpensive method for the screening of influenza A cases during an
      outbreak or pandemic situation. The cell-EIA results reflected the results
      obtained by traditional virus culture within the age distribution of samples,
      clinical symptoms, and time between date of illness onset and sampling of cases,
      indicating its usefulness in surveillance of human and non-human influenza
      viruses. During two outbreaks of influenza in schools, Directigen Flu-A, a near
      patient test, the cell-EIA, and tissue culture were compared. The cell-EIA gave
      higher sensitivity and specificity (74% and 90%) than Directigen Flu-A (65% and
      84.6%) in comparison with cell culture.

PMID- 11505460
TI  - Immunogenic and isotype-specific responses to Russian and US cold-adapted
      influenza a vaccine donor strains A/Leningrad/134/17/57, A/Leningrad/134/47/57,
      and A/Ann Arbor/6/60 (H2N2) in mice.
AB  - The immunogenicity of the Russian cold-adapted (ca) donor stains, A/Leningrad
      (Len)/134/17/57 and A/Leningrad/134/47/57, and the US strain A/Ann Arbor
      (AA)/6/60-ca, were compared in BALB/c mice with their respective wild-type
      parental viruses. Each ca donor strain was less immunogenic than its wild-type
      parent. The vaccinating dose, when administered twice, which prevented
      multiplication of a standard challenge of parental wild-type virus in 50% of mice
      (the 50% protective dose or PD(50)), was shown for A/Len/134/17/57-ca,
      A/Len/134/47/57-ca, and A/AA/6/60-ca to be 10(3.77), 10(4.32), and 10(4.70),
      respectively. These findings were extended by measuring the number of antibody
      secreting cells induced in the lungs and mediastinal lymph nodes of mice infected
      with the same ca donors using an ELISPOT assay. When each donor strain was
      administered twice at a dose of 100 PD(50) over a 3-week interval, the overall
      immunoglobulin isotype antibody secreting cell profiles were shown to be similar.
      However, A/Len/134/17/57-ca and A/Len/134/47/57-ca induced significantly higher
      total immunoglobulin responses in the lungs than A/AA/6/60-ca (P < 0.05).
      A/Len/134/17/57-ca also induced a significantly greater IgA response in the lungs
      than A/AA/6/60-ca (P < 0.05). These results suggest that A/Len/134/17/57-ca is a
      superior immunogen to A/Len/134/47/57-ca which in turn is more immunogenic than
      A/AA/6/60-ca.

PMID- 11505461
TI  - Serum and mucosal immunologic responses in children following the administration
      of a new inactivated intranasal anti-influenza vaccine.
AB  - Children are at considerable risk for influenza infection and may constitute the
      main vector for transmitting the virus to adults in the community. At present,
      the use of available vaccines in children is limited mainly because of a fear of
      side effects from the injection. Intranasal immunization was assessed as a
      painless, side effect-free method of facilitating the enrollment of children in
      vaccination programs. One intranasal dose of a trivalent inactive whole virus
      vaccine containing 20 microg of the three recommended seasonal viral strains was
      administered to 28 children recruited over two separate winter periods (1997/1998
      and 1998/1999). No adverse effects were recorded. Serum IgG responses were
      determined by the hemagglutination inhibition (HI) method and nasal IgA responses
      by enzyme-linked immunosorbent assay (ELISA). In both study period seasons, 77.7%
      94.4% of children were found to be immune. There was a 3.7 x and 4.7 x increase
      in geometric mean titer (GMT) for A/H3N2 strains, 1.9 x and 3.9 x for A/H1N1
      strains, and a 3.2 x and 1.7 x for B strains in 1997/1998 and 1998/1999,
      respectively. The increase in GMT, as well as fourfold increases in titer level,
      was higher when calculated among the nonimmune children prior to vaccination. Of
      these, 50%-87.5% became immune following immunization. Local antibody response to
      the three viral strains was detected in 50%-55% of the immunized children. Also,
      83.3%, 73.3%, and 61.1% of the vaccinees exhibited a mucosal and/or serum
      antibody response to the A/Beijing, A/Sydney, and B/Harbin strains, respectively.
      This mucosal response may forestall influenza development in its early stages,
      thereby contributing significantly to the reduction of influenza spread in the
      community.

PMID- 11505462
TI  - Reduced prevalence of serum antibodies against adeno-associated virus type 2 in
      patients with adult T-cell leukaemia lymphoma.
AB  - Seroepidemiological studies have shown previously that cancer patients are less
      likely to have antibodies against the tumour suppressive adeno-associated virus
      (AAV) than control groups. To examine the influence of AAV infection on the
      development of adult T-cell leukaemia lymphoma (ATLL), an endemic disease in
      Southern Japan that is caused by infection with the human T-cell leukaemia virus
      type 1 (HTLV-I), the prevalence of serum antibodies to AAV type 2 (AAV-2) was
      tested in healthy HTLV-I carriers (n = 39) and patients with ATLL (n = 31). The
      results showed a significant difference in AAV-2 seropositivity between the two
      groups: Only 29% of the ATLL patients had IgG antibodies against AAV-2, whereas
      84.6% of the healthy HTLV-I carriers were seropositive. Analysis of total serum
      IgG and antibodies against the Epstein-Barr virus (EBV) EBNA1 antigen showed that
      the lack of AAV antibodies in patients was not due to an ATLL-associated immune
      deficiency. The lower level of AAV-2 seropositivity in ATLL-patients may indicate
      that AAV-2 antibody-positive HTLV-I carriers might be less likely to develop ATLL
      or that loss of AAV-2 antibodies may parallel the development of disease.

PMID- 11505463
TI  - Surveillance for rotavirus in Argentina.
AB  - Group A rotaviruses are the major cause of severe gastroenteritis in young
      children worldwide. Because rotavirus vaccination appeared imminent, a nationwide
      surveillance program was organized between October 1996 and October 1998 in the
      largest Argentine cities. Surveillance for disease burden, rotavirus detection,
      and rotavirus typing was undertaken at nine locations. Results showed rotavirus
      to be associated with 42% of diarrhea admissions. Although the prevalent G types
      changed from year to year, common G types were found in 96% of the cases and were
      usually associated with common P types. Uncommon G types, G9 and G5, were found
      at low prevalence and uncommon G/P combinations occurred at almost every study
      site. These data suggest that a rotavirus vaccine could substantially decrease
      the rotavirus disease burden in Argentina, but that introduction of a vaccine
      should be accompanied by a concurrent surveillance system.

PMID- 11505465
TI  - "Race": confusion about zoological and social taxonomies, and their places in
      science.

PMID- 11505464
TI  - High detection rates of TTV-like mini virus sequences in sera from Brazilian
      blood donors.
AB  - TT virus (TTV) is an unenveloped virus with a single-stranded, circular DNA
      genome of 3,818-3,853 nucleotides (nt) that infects humans and non-human
      primates. Recently, the existence of a novel human virus, TTV-like mini virus
      (TLMV), that shows a genetic organization similar to that of TTV, but with
      smaller virion particle and genome, was proposed [Takahashi et al. (2000)
      Archives of Virology 145:979-993]. To date, no information is available with
      respect to the prevalence and pathogenicity of TLMV. A sensitive PCR assay was
      developed by using two oligonucleotide primers (LS2 and LA2) designed from the
      conserved non-coding region of the TLMV genome. One hundred thirty-seven sera
      from volunteer Brazilian blood donors were tested and 99 (72%) were TLMV DNA
      positive. No significant differences were observed between the groups of TLMV
      positive and negative subjects in relation to sex ratio, seroprevalence of TTV
      DNA, prevalence of anti-hepatitis A virus antibodies, area of residence,
      occurrence of daily contact with animals, family income, education level, and
      level of alanine aminotransferase. The specificity of the PCR assay was
      demonstrated after cloning of amplification products and determination of the
      nucleotide sequences (200-228 nt) of clones derived from 23 individuals. When
      DNAs extracted from TLMV/TTV-coinfected sera were submitted to PCR with LS2 and
      LA2 primers, the amplification products were derived exclusively from the TLMV
      genome. A markedly wide range of sequence divergence, even higher than that
      existent among TTV strains, was noted among TLMV isolates, with a maximum
      evolutionary distance of 0.80.

PMID- 11505466
TI  - Mitochondrial DNA sequence analysis in Sicily.
AB  - This study reports data on the sequences of the first hypervariable segment of a
      sample of the Sicilian population from Alia (Palermo, Italy). The results show
      the presence of 32 different haplotypes in the 49 individuals examined. The
      average number of pairwise nucleotide differences was 4.04, i.e., 1.17% per
      nucleotide. The distribution of the nucleotide differences matches the
      theoretical distribution and indicates only one major episode of expansion that
      occurred between 20,732 and 59,691 years ago, between the Middle Paleolithic and
      Upper Paleolithic. Compared with the other populations, parameters of the
      Sicilian sample lie in an intermediate position between the eastern and western
      Mediterranean populations. This is due to numerous contacts that Sicily has had
      with the Mediterranean area since prehistoric times. At the same time, the
      singularity of some of the haplotypes present in the sample studied indicates the
      persistence of some characteristics caused by genetic drift and isolation that
      the population has endured in the course of its history.

PMID- 11505467
TI  - Well-being changes in response to 30 years of regional integration in Maya
      populations from Yucatan, Mexico.
AB  - Infant mortality rate (IMR), overall frequency of linear enamel hypoplasia (LEH),
      sexual dimorphism in LEH, age of onset of LEH, and age at menarche were used as
      indicators to test the hypothesis that the origin and development of the tourist
      industry and increased state participation on Maya subsistence agriculturists in
      the early 1970s had improved the well-being of the Maya. Two historical moments
      where inferred from the data. The first was derived from cheap and effective
      immunization and sanitation campaigns that reduced IMR from 143.4/1,000 live
      births in the early 1960s to 97.4 in the early 1970s. State participation broke
      the undernutrition-disease cycle enough to reduce LEH frequencies significantly
      (from 71.9% in individuals born before 1971 to 51.5% in those born in 1971 or
      after, chi(2) = 55.72; 1 df; alpha = 0.00001) and to eliminate the sex difference
      in LEH expression (from a 14.8% LEH difference between men and women before 1971
      [Male/Female Odds Radio = 0.45, alpha significant at 0.05] to a nonsignificant 2%
      difference). Improvement in overall living conditions reflected in a "modern
      stage" infant mortality regime and an almost disappearance of LEHs, resulted from
      gradual improvements in living conditions that did not become apparent until the
      1980s. Trends in the age at menarche are not statistically significant, probably
      due to methodological limitations. However, if overall living conditions continue
      to improve or stay as they are today, accelerations in maturation should become
      noticeable.

PMID- 11505468
TI  - Assessment of the growth of children and physical status of adults in two
      Aboriginal communities in South Australia.
AB  - Growth of children and physical status of adults in two Aboriginal communities,
      Gerard and Raukkan, South Australia, were assessed. Height, weight, biepicondylar
      breadth of humerus, the triceps and subscapular skinfolds, and arm circumferences
      were measured on 110 children and 77 adults annually between 1996 and 2000. Data
      were transformed to z scores, using American reference data. In all groups height
      z scores are negative. In all but Raukkan boys, the z scores are significantly
      smaller than the reference. Body weight z scores lie above the reference, with
      the only exceptions being Gerard children. Still, in all cases BMI lies above the
      reference, being significantly greater than the reference, except in Gerard
      girls. z scores for the triceps skinfold are not consistently positive, but those
      for the subscapular skinfold are positive in all groups, indicating centralized
      fat accumulation. In both boys and girls, Raukkan men and Gerard women,
      biepicondylar breadth of the humerus is below the reference. Increased BMI and
      trunk fatness suggest that members of these communities are not only receiving
      adequate nutrition, but that in many cases there is also a caloric surplus,
      sometimes leading to obesity. Inadequate skeletal growth indicated by short
      stature and small biepicondylar breadths, on the other hand, suggests that the
      environment is less than optimal for growth. Factors such as disease load,
      psychosocial pressures, or specific nutrient shortages may be involved.

PMID- 11505469
TI  - Muscularity in adult humans: proportion of adipose tissue-free body mass as
      skeletal muscle.
AB  - Muscularity, or the proportion of adipose tissue-free body mass (ATFM) as
      skeletal muscle (SM), provides valuable body composition information, especially
      for age-related SM loss (i.e., sarcopenia). Limited data from elderly cadavers
      suggest a relatively constant SM/ATFM ratio, 0.540 +/- 0.046 for men (mean +/-
      SD, n = 6) and 0.489 +/- 0.049 for women (n = 7). The aim of the present study
      was to examine the magnitude and constancy of the SM/ATFM ratio in healthy
      adults. Whole-body SM and ATFM were measured using multi-scan magnetic resonance
      imaging. The SM/ATFM ratio was 0.528 +/- 0.036 for men (n = 139) and 0.473 +/-
      0.037 for women (n = 165). Multiple regression analysis indicated that the
      SM/ATFM ratio was significantly influenced by sex, age, body weight, and race.
      The four factors explained 50% of the observed between individual variation in
      the SM/ATFM ratio. After adjusting for age, body weight, and race, men had a
      larger SM/ATFM ratio than women. Both older men and women had a lower SM/ATFM
      ratio than younger subjects, although the relative reduction was greater in men.
      After adjustment for sex, age, and body weight, there were no significant
      differences in the SM/ATFM ratios between Asian, Caucasian, and Hispanic
      subjects. In contrast, African-American subjects had a significantly greater
      SM/ATFM ratio than subjects in the other three groups. In addition, the SM/ATFM
      ratio was significantly lower in AIDS patients than corresponding values in
      healthy subjects.

PMID- 11505470
TI  - Familial risk of high blood pressure in the Canadian population.
AB  - Familial risk ratios for high blood pressure were estimated in a representative
      sample of the Canadian population. The sample consisted of 14,069 participants 7
      69 years of age from 5,753 families participating in the 1981 Canada Fitness
      Survey. Resting systolic (SBP) and diastolic (DBP) blood pressures were adjusted
      for the effects of body mass index using regression procedures. Varying degrees
      of high blood pressure were defined as the 75(th), 85(th), and 95(th) percentiles
      of age- and sex-specific values. Age- and sex-standardized risk ratios (SRRs)
      were calculated comparing the prevalences in the general population to those in
      spouses and first-degree relatives of probands with high blood pressure. SRRs for
      the 95(th) percentile were, for SBP and DBP, respectively, 1.37 and 1.45 in
      spouses and 1.33 and 2.36 in first-degree relatives of probands. SRRs decrease
      with decreasing percentile cut-offs used to define high blood pressure (95(th) >
      85(th) > 75(th)), and SRRs are generally higher in first-degree relatives than in
      spouses, particularly for DBP. The results indicate significant familial risk for
      high blood pressure in the Canadian population, and the pattern of SRRs suggests
      that genetic factors may be responsible for a portion of the risk.

PMID- 11505471
TI  - Climate and head form in India.
AB  - The relationship between head form and climatic variation was investigated in
      different tribal and caste populations of India. The magnitude of the cephalic
      index varies significantly in different zones. In tropical zones, head form is
      longer (dolicocephalic), but in temperate zones, head form is more round
      (mesocephalic or brachycephalic), especially among Scheduled Tribes (ST) and
      Scheduled Castes (SC) than among other castes. These trends possibly support a
      climatic adaptation model in head form differences among ST and SC in India.

PMID- 11505472
TI  - Tibetan protection from intrauterine growth restriction (IUGR) and reproductive
      loss at high altitude.
AB  - Chronic hypoxia at high altitude restricts fetal growth, reducing birth weight
      and increasing infant mortality. We asked whether Tibetans, a long-resident high
      altitude population, exhibit less altitude-associated intrauterine growth
      restriction (IUGR) and prenatal or postnatal reproductive loss than Han (ethnic
      Chinese), a group that has lived there for a shorter period of time. A population
      sample was obtained, comprising 485 deliveries to Tibetan or Han women over an 18
      month period at 8 general hospitals or clinics located at 2,700-4,700 m in the
      Tibet Autonomous Region, China. Birth weight, gestational age, and other
      information were recorded for each delivery. Prenatal and postnatal mortality
      were calculated using information obtained from all pregnancies or babies born to
      study participants. Tibetan babies weighed more than the Han, averaging 310 g
      heavier at altitudes 2,700-3,000 m (95% CI = 126, 494 g; P < 0.01) and 530 g
      heavier at 3,000-3,800 m (210, 750 g; P < 0.01). More Han than Tibetan babies
      were born prematurely. Prenatal and postnatal mortality rose with increasing
      elevation and were 3-fold higher across all altitudes in the Han than the
      Tibetans (P < 0.05). Tibetans experience less altitude-associated IUGR than Han
      and have lower levels of prenatal and postnatal mortality. When the relationships
      between birth weight and altitude are compared among these and other high
      altitude populations, those living at high altitude the longest have the least
      altitude-associated IUGR. This may suggest the occurrence of an evolutionary
      adaptation.

PMID- 11505473
TI  - Intergenerational correlation of effective family size in early Quebec (Canada).
AB  - The use of a comprehensive demographic database of the early French Canadian
      population (1608-1800) reveals an almost null impact of parents' fertility on
      children's fertility (r approximately 0.01-0.05), which contradicts the commonly
      held view that family size has a tendency to run in families. However, in this
      population, there is a clear transmission from one generation to the next of the
      effective family size within a given geographical area (EFS, defined as the
      number of children that settle per settled individual). Three types of
      correlations between EFS of parents and children are presented in order to
      account for the impact of socio-demographic differentials. Individuals who belong
      to a large sibship and who settled in a given subdivision tend to encourage the
      settlement of a high number of their own children in the same subdivision (r
      approximately 0.1-0.3). An additional correlation was introduced to see if
      geographically-based differentials of EFS can account for the differential of
      founders' regional genetic contribution. The analysis shows that EFS correlation
      has a definite impact on the concentration of a population's gene pool (it
      increases it by approximately 20%-45%), and partly accounts for the differences
      between subdivisions in this regard.

PMID- 11505474
TI  - New genetic data on Amerindians from the Paraguayan Chaco.
AB  - New data on 17 blood group and protein genetic systems obtained among the Ayoreo
      and Lengua Indians of Paraguay are presented. They include the first report on
      the red cell band-3 protein investigated among South American Indians. This
      information was integrated with previous results available for these two and four
      other groups. Five of the six populations reside in the Chaco area, while the
      sixth was included as an outgroup living elsewhere in Paraguay. Four of the five
      Chaco tribes exhibit good genetic homogeneity, but the Ayoreo are somewhat
      different. The results confirm the Chaco as a distinct biological (as well as
      cultural and economic) region, which should be considered in evaluations of
      genetic variability among South American Indians.

PMID- 11505475
TI  - Nutritional status by socioeconomic level in an urban sample from Bilbao (Basque
      Country).
AB  - Anthropometry, records of food intake, and bioelectric impedance were gathered
      from a sample of 297 adults of both sexes who lived in marginal districts in the
      town of Bilbao and benefited from a program of social assistance. This survey
      aimed to determine present nutritional status and to ascertain the relationship
      between food intake and nutritional conditions. A comparative evaluation of
      anthropometry and food intake was then carried out using a reference from the
      Basque Country and a control sample from the same area but from better-off
      nutritional and socioeconomic conditions. Males from low socioeconomic status
      (SES) displayed lower heights and weights compared to the local reference and
      control sample. They showed higher skinfold thickness than males in the local
      reference but lower thicknesses than those in the control sample. All
      anthropometric variables, except height, were higher in women of low
      socioeconomic status compared to the local reference and control sample. Low
      socioeconomic males had lower estimated percentage of body fat than the control
      sample, while females showed the opposite pattern. On the other hand, estimates
      of food intake in males did not reveal great differences among samples from
      different socioeconomic backgrounds, while low SES females had greater intakes of
      food than the better-off control sample. Estimated zinc intake showed differences
      by SES in both sexes.

PMID- 11505476
TI  - Child abuse and the balance of power in parental relationships: an evolved domain
      independent mental mechanism that accounts for behavioral variation.
AB  - Previous studies use zero-order analyses to show a link between child abuse and
      exposure to "stepfathers." These studies rest on a proposed evolved, domain
      specific cognitive mechanism that induces adult males to abuse or kill offspring
      not their own and, so, contribute directly to reproductive success. However,
      child abuse may reflect an evolved neurological mechanism that creates behavioral
      plasticity and adaptability by assigning emotional weights (which in
      consciousness appear rationalized as costs and benefits) to choice alternatives
      in all behavioral domains. This mechanism should act as a selective mechanism to
      create enhanced ability to avoid predation (social exploitation) and to obtain
      access to resources, given the properties of specific ecosystems, and should
      control behavioral responses to variation in the balance of power in social
      relationships. Power equalities should elicit good treatment for both parties;
      power inequalities, by contrast, should elicit exploitative and coercive behavior
      on the part of those who hold the balance of power. This paper reports a test of
      both hypotheses simultaneously, controlling for a standard social science risk
      factor (growing up in poverty). Once we control for the balance of power in
      parental relationships, exposure to a stepfather and growing up in poverty show
      no effect on the intensity of child abuse. Powerful women negotiated affectionate
      behavior from their partners for both themselves and their children; powerless
      women's negotiations with partners usually left both themselves and their
      children open to violence.

PMID- 11505477
TI  - Effect of Down syndrome on the dimensions of dental crowns and tissues.
AB  - Abnormal growth in Down syndrome (DS) is reflected by variable reduction in size
      and simplification in form of many physical traits. This study aimed to compare
      the thickness of enamel and dentine in deciduous and permanent mandibular incisor
      teeth between DS and non-DS individuals and to clarify how these tissues
      contribute to altered tooth size in DS. Sample groups comprised 61 mandibular
      incisors (29 permanent and 32 deciduous) from DS individuals and 55 mandibular
      incisors (29 permanent and 26 deciduous) from non-DS individuals. Maximum
      mesiodistal and labiolingual crown dimensions were measured initially, then the
      crowns were sectioned midsagittally and photographed using a stereomicroscope.
      Linear measurements of enamel and dentine thickness were obtained on the labial
      and lingual surfaces of the crowns, together with enamel and dentine-pulp areas
      and lengths of the dentino-enamel junction. Reduced permanent crown size in DS
      was associated with a reduction in both enamel and dentine thickness. After
      adjustments were made for tooth size, DS permanent incisors had significantly
      thinner enamel than non-DS permanent teeth. The DS permanent teeth also exhibited
      significant differences in shape and greater variability in dimensions than the
      non-DS permanent teeth. Crown dimensions of deciduous incisors were similar in
      size or larger in DS compared with non-DS deciduous teeth. Enamel and dentine
      thicknesses of the deciduous teeth were similar in DS and non-DS individuals. The
      findings indicate that growth retardation in DS reduces both enamel and dentine
      deposition in the permanent incisors but not in the earlier-forming deciduous
      predecessors. The results are also consistent with the concept of amplified
      developmental instability for dental traits in DS.

PMID- 11505478
TI  - Carcinoma ex pleomorphic adenoma: a clinicopathologic review.
AB  - BACKGROUND: Carcinoma ex pleomorphic adenoma (CXPA) is an aggressive, poorly
      understood salivary gland malignancy. Misdiagnosis is common, because the
      residual mixed tumor component may be small, and various carcinoma subtypes are
      possible. METHODS: We retrospectively reviewed the medical records of 73 patients
      with major salivary gland CXPA treated at our institution from 1960 to 1994. Of
      the 73 patients, 66 had primary tumors and 7 had recurrent tumors; 47 were men,
      and 26 were women; the mean age was 61 years. RESULTS: Adenocarcinoma (31 cases)
      and salivary duct carcinoma (24 cases) were the most common malignant subtypes.
      All patients were treated surgically, and 32 also had radiation therapy. Of 66
      patients with primary tumors, 23% had local recurrence. Metastasis (either
      initial or delayed) occurred regionally in 56% and distantly in 44%. Thirty-six
      patients (55%) died of the disease. At 3 years, overall survival was 39% and at 5
      years, 30%. CONCLUSIONS: Important prognostic factors include tumor size, grade,
      and clinical and pathologic stage. Patients with minimally invasive tumors (<5
      mm) should do well with appropriate surgical treatment.

PMID- 11505479
TI  - Advanced hypopharyngeal carcinoma treatment results according to treatment
      modalities.
AB  - BACKGROUND: The purpose of this retrospective study is to compare the treatment
      results of locally advanced hypopharyngeal carcinoma according to treatment
      modalities. METHODS: Seventy-three patients with locally advanced hypopharyngeal
      carcinoma treated at the Department of Therapeutic Radiology, Seoul National
      University Hospital, between August 1979 and July 1997 were retrospectively
      analyzed. Twenty-three patients were treated with radiotherapy (RT) alone, 18
      patients were treated with surgery and postoperative RT, and 32 patients were
      treated with neoadjuvant chemotherapy (CTx) and RT. Median follow-up period was
      28 months. RESULTS: The overall 5-year survival rates were 15.7% for the RT alone
      group, 46.8% for surgery and postoperative RT group, and 43.0% for neoadjuvant
      CTx and RT group. The 5-year disease-free survival rates were 13.9%, 47.4%, and
      30.7%, respectively. Surgery and postoperative RT or neoadjuvant CTx and RT
      showed superiority over RT alone in terms of both overall survival and disease
      free survival rates. No significant differences were found in overall and disease
      free survival rates between the surgery and postoperative RT group and
      neoadjuvant CTx and RT group (p =.15, p =.13). In the neoadjuvant CTx and RT
      group, 12 patients (38%) retained their larynx more than 5 years. CONCLUSION:
      Neoadjuvant CTx and RT is an effective strategy to achieve organ preservation
      without compromising the survival of patients with locally advanced
      hypopharyngeal carcinoma.

PMID- 11505480
TI  - Prediction of survival in patients with head and neck cancer.
AB  - BACKGROUND: In patients with head and neck squamous cell carcinoma (HNSCC) the
      estimated prognosis is usually based on the TNM classification. The relative
      weight of the three contributing parameters is often not completely clear.
      Moreover, the impact of other important clinical variables such as age, gender,
      prior malignancies, etc is very difficult to substantiate in daily clinical
      practice. The Cox-regression model allows us to estimate the effect of different
      variables simultaneously. The purpose of this study was to design a model for
      application in new HNSCC patients. In our historical data-base of patients with
      HNSCC, patient, treatment, and follow-up data are stored by trained oncological
      data managers. With these hospital-based data, we developed a statistical model
      for risk assessment and prediction of overall survival. This model serves in
      clinical decision making and appropriate counseling of patients with HNSCC.
      PATIENTS AND METHODS: All patients with HNSCC of the oral cavity, the pharynx,
      and the larynx diagnosed in our hospital between 1981 and 1998 were included. In
      these 1396 patients, the prognostic value of site of the primary tumor, age at
      diagnosis, gender, T-, N-, and M-stage, and prior malignancies were studied
      univariately by Kaplan-Meier curves and the log-rank test. The Cox-regression
      model was used to investigate the effect of these variables simultaneously on
      overall survival and to develop a prediction model for individual patients.
      RESULTS: In the univariate analyses, all variables except gender contributed
      significantly to overall survival. Their contribution remained significant in the
      multivariate Cox model. Based on the relative risks and the baseline survival
      curve, the expected survival for a new HNSCC patient can be calculated.
      CONCLUSIONS: It is possible to predict survival probabilities in a new patient
      with HNSCC based on historical results from a data-set analyzed with the Cox
      regression model. The model is supplied with hospital-based data. Our model can
      be extended by other prognostic factors such as co-morbidity, histological data,
      molecular biology markers, etc. The results of the Cox-regression may be used in
      patient counseling, clinical decision making, and quality maintenance.

PMID- 11505481
TI  - Transforming growth factor beta1, urokinase-type plasminogen activator and
      plasminogen activator inhibitor-1 mRNA expression in head and neck squamous
      carcinoma and normal adjacent mucosa.
AB  - BACKGROUND: A balance between urokinase-type plasminogen activator (uPA) and its
      main inhibitor type-1 (PAI-1) appears to be important for cancer invasive
      behavior. Since uPA/PAI-1 system seems to be regulated by transforming growth
      factor beta1 (TGFbeta1) in different cell types, our aim was to investigate the
      relationship between the expression of the three genes and lymph node status in
      head and neck squamous cell carcinomas (HNSCC) at specific sites. MATERIALS AND
      METHODS: uPA, PAI-1, and TGFbeta1 mRNAs were determined by Northern analysis in
      tumor, and paired normal mucosa samples were obtained from 91 operable HNSCC
      patients. RESULTS: In oral cavity, excluding tongue, TGFbeta1, PAI-1, and uPA
      mRNAs values were consistently lower in the normal tissues than in tumors. In
      larynx tumors, TGFbeta1 expression was increased, but no statistically
      significant differences were found for uPA or PAI-1 mRNAs as compared with normal
      tissues. Tongue tumors overexpressed only uPA mRNA, and uPA levels showed
      significant parallel variations with TGFbeta1 and PAI-1 mRNAs mainly in pN+
      tumors. In oral cavity tumors, an inverse correlation between TGFbeta1 and uPA
      was observed in pN0 subgroup, elevated uPA mRNA was counterbalanced by high PAI-1
      mRNA TGFbeta1, and PAI-1 were not coordinately expressed. Correlations between
      the three markers were not found in larynx. Hypopharynx tumors, all staged as
      pN+, expressed the lowest TGFbeta1 mRNA mean values. CONCLUSIONS: Combined
      information about TGFbeta1, uPA, and PAI-1 mRNAs may add some clues to the
      understanding of the pathophysiological role of uPA system in head and neck
      squamous cell carcinoma.

PMID- 11505482
TI  - Results of salvage surgery for local or regional recurrence after larynx
      preservation with induction chemotherapy and radiotherapy.
AB  - BACKGROUND: After treatment of locally advanced laryngeal carcinomas with
      induction chemotherapy and radiotherapy, some patients suffer a local or regional
      failure of the tumor, and salvage surgery is required. The aim of this study was
      to review the results of such salvage surgery in this group of patients. METHODS:
      A retrospective study of a cohort of 110 patients diagnosed between 1989 and 1996
      with a locally advanced laryngeal carcinoma (T3-T4) treated with induction
      chemotherapy and radiotherapy was performed. The results of salvage surgery in
      patients with a local and/or regional failure of the treatment were analyzed.
      RESULTS: Forty-two patients presented a local and/or a regional recurrence of the
      tumor: 26 patients in the larynx, eight in the neck, and a further eight in both
      in the larynx and the neck. Salvage surgery was carried out in 28 patients (67%),
      consisting of total laryngectomies with neck dissections (24 cases), endoscopic
      resection of the tumor (one case), and radical neck dissections (three cases).
      Five-year adjusted survival for the 42 patients was 38%. Five-year survival for
      the 28 patients treated with salvage surgery was 57%. Five patients had
      postoperative complications: four had pharyngo-cutaneous fistulas and one had
      wound infection. CONCLUSIONS: After a local and/or regional recurrence, 67% of
      patients with advanced laryngeal carcinoma treated with induction chemotherapy
      and radiotherapy were candidates to salvage surgery. Five-year adjusted survival
      for this group of patients was 57%.

PMID- 11505483
TI  - Observer error in the assessment of nodal disease in head and neck cancer.
AB  - BACKGROUND: There is no previously published information on clinicians' abilities
      to accurately differentiate between different stages of node positive disease in
      head and neck cancer. METHODS: Forty-two surgeons examined standardized nodes in
      a model neck and estimated nodal size. Each recorded their confidence in their
      ability to perform the task using a visual analogue scale. Reference nodes of
      known size were provided for comparison during a second examination of each node.
      The study was repeated after 1 month. RESULTS: Accuracy was poor and was not
      dependent on experience or confidence. There was a tendency to underestimate the
      size of smaller nodes. Estimates were strongly influenced by volume independent
      of largest diameter (p <.001). Reference nodes aided accuracy (p =.031). Subjects
      were not consistent on repeated testing (p <.001). CONCLUSIONS: Both trainees and
      specialists are poor at accurately staging nodal disease using palpation alone.

PMID- 11505484
TI  - Incidence of cervical node involvement in metastatic cutaneous malignancy
      involving the parotid gland.
AB  - BACKGROUND: The parotid lymph nodes represent an important group of nodes at risk
      for metastatic involvement from cutaneous malignancies of the head and neck. When
      treating patients with metastatic disease in the parotid gland it has been our
      custom to also remove the lymph nodes of the neck on the basis that these nodes
      represent other nodal groups at risk for metastatic involvement. The aim of this
      study is to determine the incidence of cervical node involvement among patients
      with clinical metastatic SCC or melanoma of the parotid to determine whether
      treatment of the clinically negative neck is warranted. METHODS: The study group
      consists of 123 prospectively accessioned patients with clinical metastatic
      cutaneous squamous cell carcinoma (SCC) (n = 73) or melanoma (n = 50) involving
      the parotid gland and a minimum of 2 years of follow up, irrespective of the
      clinical status of the neck. RESULTS: Among 73 patients with metastatic SCC in
      the parotid, 19 (26%) had clinical neck involvement, and 16 of these were
      pathologically positive (84%). A total of 37 patients had elective neck
      dissections, and 13 were pathologically positive, which is an overall rate of 52%
      neck involvement among patients having neck dissection. Among 50 patients with
      metastatic melanoma in the parotid, 19 (38%) patients were initially seen with
      clinical neck disease, and all were pathologically positive. Among 31 patients
      with clinically negative necks, 26 had neck dissections and seven had positive
      nodes (27%). Overall, 58% of patients with melanoma who had a neck dissection had
      positive nodes. CONCLUSION: Patients with metastatic cutaneous SCC and melanoma
      involving the parotid gland had a high incidence of clinical (26% and 38%,
      respectively) and occult neck disease (35% and 27%). Treatment of the clinically
      negative neck in the presence of clinical metastatic parotid cancer should be
      considered to reduce the likelihood of failure in cervical nodes, to define the
      extent of disease, and to assist with patient selection for adjuvant therapy.

PMID- 11505485
TI  - Esthesioneuroblastoma: the impact of treatment modality.
AB  - BACKGROUND: We evaluated the impact of treatment modality on
      esthesioneuroblastoma. METHODS: Between 1976 and 1996, 25 patients with
      esthesioneuroblastoma were treated at Mallinckrodt Institute of Radiology. There
      were 11 male and 14 female patients; their ages ranged from 16 to 73 years
      (median, 57 years). The tumors were Kadish stage A in 3, Stage B in 13, C in 8,
      and modified D in 1 (cervical nodal metastasis). Seventeen patients were treated
      with surgery and radiation therapy, six were treated with irradiation alone, and
      two were treated with surgery only. Eight patients received neoadjuvant
      chemotherapy. Median follow-up was 8 years (range, 2-24 years). RESULTS: The 5
      year actuarial overall survival, disease-free survival, and local tumor control
      rates were 66.3%, 56.3%, and 73.0%, respectively. Kadish stage was not a
      significant prognosticator for local control or disease-free survival. Five-year
      local control rates were 87.4% for the combination of surgery and radiation
      therapy and 51.2% for irradiation alone. Two patients with Kadish stage A and B
      disease underwent surgical resection alone; both failed locally. In contrast,
      33.3% of patients (three of nine) with Kadish stage A or B disease who received
      adjuvant radiation therapy had a local recurrence develop. With adjuvant
      radiation therapy, the surgical margin status did not influence local tumor
      control. Among the eight patients who received neoadjuvant chemotherapy, six
      patients showed no response, one had partial response, and one showed a complete
      response. CONCLUSIONS: Surgical resection plus adjuvant radiation therapy yielded
      the best treatment outcome. More effective chemotherapy agents with a
      reproducible effectiveness are needed for patients with locally advanced
      esthesioneuroblastoma.

PMID- 11505486
TI  - Cancer of retromolar trigone: long-term radiation therapy outcome.
AB  - BACKGROUND: Cancer of the retromolar trigone is an uncommon head and neck cancer.
      In this retrospective study, we identified the prognostic factors and evaluated
      the therapeutic outcomes of patients treated with preoperative radiation therapy
      (RT), postoperative RT, and RT alone. METHODS: Between 1971 and 1994, 65 patients
      with histologically proven epidermoid carcinoma of the retromolar trigone were
      treated at the Mallinckrodt Institute of Radiology; 10 patients received
      preoperative RT (30-55.2 Gy), 39 received postoperative RT (46-66.6 Gy), and 15
      were treated with RT alone (63-74 Gy). Surgery included 44 composite resections
      and 7 wide excisions. The minimum follow-up was 5 years. RESULTS: The 5-year
      disease-free survival rates were 90% with preoperative RT, 63% with postoperative
      RT, and 31% with RT alone. The 5-year disease-free survival rates were 76% for
      patients with T1 disease, 50% for T2, 72% for T3, and 54% for T4. The 5-year
      disease-free survival rates were 69% for patients with NO disease, 56% for N1,
      and 26% for N2. The locoregional recurrence rates were 10% (1 of 10) for
      preoperative RT, 23% (9 of 39) for postoperative RT, and 44% (7 of 16) for RT
      alone. On multivariate analysis, the significant factors for disease-free
      survival were treatment modality (p =.002) and N stage (p =.012); for
      locoregional control it was treatment modality (p =.046); and for distant
      metastasis it was N stage (p =.002). The incidence of bone necrosis, soft tissue
      necrosis, and severe trismus was 12% with postoperative RT, 11% with RT alone,
      and none with preoperative RT. CONCLUSIONS: Combination surgery with
      postoperative or preoperative RT offers better locoregional control and disease
      free survival than RT alone for epidermoid carcinoma of the retromolar trigone.
      Lymph node status significantly influences the disease-free survival and distant
      metastasis rates.

PMID- 11505487
TI  - Effects of chemotherapy on invasion and metastasis of oral cavity cancer in mice.
AB  - BACKGROUND: Using an orthotopic implantation model in which oral cancer invasion
      and metastasis can be reproduced, we investigated the inhibitory effects of
      anticancer agents on invasion and metastasis. METHODS: A highly invasive and
      metastatic human oral squamous cell carcinoma cell line, OSC-19, was implanted
      into the oral floor of nude mice, and cisplatin or peplomycin was administered to
      the mice 7 or 14 days after implantation. The effects of each anticancer drug and
      different administration timings on cancer invasion and metastasis were
      investigated. RESULTS: Tumor size and the ratio of proliferating cell nuclear
      antigen-positive cells was significantly reduced. In the control group, the
      tumors showed grade 4C mode of invasion, whereas in the groups treated with
      anticancer drugs, grade 3 was observed in 77.3% of the mice, with an inhibitory
      effect on tumor invasion being observed. The rate of metastasis in the cervical
      lymph node was significantly decreased in the groups treated with the cisplatin
      or peplomycin on day 7 after implantation. The tumor stage progression in the
      metastatic lymph nodes was also inhibited. CONCLUSIONS: Chemotherapy is effective
      not only for tumor diminution but also for inhibiting invasion and metastasis. In
      light of these effects, administration of anticancer drugs may be clinically
      useful in this regard.

PMID- 11505488
TI  - Neck and mediastinal node dissection in pharyngolaryngoesophageal tumors.
AB  - BACKGROUND: Specific reports about neck node metastasis in cervical esophageal
      tumors and mediastinal node metastasis in patients with pharyngolaryngoesophageal
      tumors are lacking. This study was undertaken to evaluate the need for neck and
      mediastinal lymph node dissection when dealing with carcinomas of this region.
      METHODS: A retrospective review of the records of 34 patients who underwent total
      pharyngolaryngoesophagectomy and gastric transposition (TPLEGT) for squamous cell
      carcinoma of the pharyngoesophageal junction was done. Sixteen patients had
      esophageal carcinomas, 14 had hypopharyngeal carcinomas, and 4 had laryngeal
      carcinomas. The mediastinal dissection was designed to remove mainly the
      paratracheal and paraesophageal lymph nodes down to the aortic arch, without
      thoracotomy. Neck and mediastinal lymph node metastases were studied with
      specific reference to main primary site, and comparison with the literature was
      undertaken. RESULTS: Twenty-five neck dissections were performed in 19 patients
      and yielded positive nodes in 16 patients (47% of all patients). The neck nodes
      were positive in 75%, 64.2%, and 18.7% of the patients with laryngeal,
      hypopharyngeal, and esophageal carcinomas, respectively. Mediastinal dissection
      data were available on 27 patients, and 16 (59.2%) had mediastinal node
      metastasis. These mediastinal nodes were positive in 0%, 72.7%, and 61.5% of the
      patients with laryngeal, hypopharyngeal, and esophageal carcinomas, respectively.
      CONCLUSIONS: There is little controversy about neck dissections in tumors of the
      larynx and hypopharynx when a TPLEGT is contemplated. A similar situation applies
      to mediastinal dissections for cervical esophageal carcinomas. Although we
      observed a low incidence of positive neck nodes (18.7%) in patients with cervical
      esophageal carcinomas, there is a need for a larger prospective series. Our
      finding of 72.7% positive mediastinal nodes in hypopharyngeal carcinomas is high
      enough to deserve further study. Laryngeal carcinomas showed no positive
      mediastinal nodes in this series.

PMID- 11505489
TI  - Clinically underdetected asymptomatic and symptomatic carotid stenosis as a late
      complication of radiotherapy in Chinese nasopharyngeal carcinoma patients.
AB  - BACKGROUND: Carotid artery stenosis is a late complication of radiotherapy to the
      neck region. This complication has, however, a significant impact with increased
      risk of stroke causing mortality and morbidity. Clinicians' awareness of this
      complication and early detection is therefore important. METHODS: Eighty patients
      with nasopharyngeal carcinoma (NPC) who had received radiotherapy were recruited
      for color Doppler ultrasonography of the carotid arteries. fifty-eight patients
      with newly diagnosed NPC who had never received any radiotherapy were recruited
      as controls. All patients with significant carotid stenosis were referred to the
      neurology clinic for further assessment. RESULTS: Twenty-four patients were found
      to have more than 50% diameter reduction in the extracranial carotid artery.
      Clinical assessment by a neurologist showed 9 of 24 patients had a history of
      transient ischemic attack, amaurosis fugax, or stroke. Seven of these patients
      had clinically detectable neck bruit. CONCLUSIONS: Clinicians attending to
      patients after radiotherapy for head and neck cancers should be aware of this
      long-term complication of radiotherapy. A detailed clinical history and
      incorporation of auscultation of carotid arteries in routine follow-up of
      postradiotherapy patients are recommended.

PMID- 11505490
TI  - Do nodal metastases from cutaneous melanoma of the head and neck follow a
      clinically predictable pattern?
AB  - BACKGROUND: Potential lymphatic drainage patterns from cutaneous melanomas of the
      head and neck are said to be variable and frequently unpredictable. The aim of
      this article is to correlate the anatomic distribution of pathologically involved
      lymph nodes with primary melanoma sites and to compare these findings with
      clinically predicted patterns of metastatic spread. METHODS: A prospectively
      documented series of 169 patients with pathologically proven metastatic melanoma
      was reviewed by analyzing the clinical, operative, and pathologic records.
      Clinically, it was predicted that melanomas of the anterior scalp, forehead, and
      face could metastasize to the parotid and neck levels I-III; the coronal scalp,
      ear, and neck to the parotid and levels I-V; the posterior scalp to occipital
      nodes and levels II-V; and the lower neck to levels III-V. Minimum follow up was
      2 years. RESULTS: There were 141 therapeutic (97 comprehensive, 44 selective) and
      28 elective lymphadenectomies (4 comprehensive dissections, 21 selective neck
      dissections, and 3 cases in which parotidectomy alone was performed). Overall,
      there were 112 parotidectomies, 44 of which were therapeutic and 68 elective.
      Pathologically positive nodes involved clinically predicted nodal groups in 156
      of 169 cases (92.3%). The incidence of postauricular node involvement was only
      1.5% (3 cases). No patient was initially seen with contralateral metastatic
      disease; however, 5 patients (2.9%) failed in the contralateral neck after
      therapeutic dissection. In 68% of patients, metastatic disease involved the
      nearest nodal group, and in 59% only a single node was involved. CONCLUSIONS:
      Cutaneous malignant melanomas of the head and neck metastasized to clinically
      predicted nodal groups in 92% of patients in this series. Postauricular and
      contralateral metastatic node involvement was uncommon.

PMID- 11505491
TI  - Salvage treatment for persistent and recurrent T1-2 nasopharyngeal carcinoma by
      stereotactic radiosurgery.
AB  - OBJECTIVE: To study the efficacy of stereotactic radiosurgery in salvaging early
      stage persistent and recurrent nasopharyngeal carcinoma (NPC) after primary
      radiotherapy. METHODS: A prospective single-arm study evaluating the response and
      outcome of patients with rT1-2 NPC treated by stereotactic radiosurgery. Eleven
      patients with rT1-2 were treated by radiosurgery between March 1998 and March
      2000. Four patients were treated for persistent disease occurring within 4 months
      after primary radiotherapy, six were treated for first recurrence, and one for
      third recurrence. Six patients had rT1 disease and five had rT2 disease. Most
      patients had disease not amenable to brachytherapy, surgery, or external re
      irradiation. The median target volume was 5.8 cc (range, 3.3-16.9). Radiosurgery
      was performed with multiple noncoplanar arcs of photon, with a median dose of
      12.5 Gy delivered to the 80% isodose line (range, 12-14 Gy). Median follow-up
      time after radiosurgery was 18 months (range, 9-30). RESULTS: Nine patients had
      complete regression of tumor as assessed by imaging, nasopharyngoscopy, and
      biopsy; one patient had partial regression of tumor; whereas one patient had
      static disease. The overall response rate was 91% (10 of 11) and the complete
      response rate was 82% (9 of 11). Two patients with complete response subsequently
      had local relapse develop, with one recurrence outside the treated volume 8
      months after radiosurgery, and the other within the treated volume 6 months after
      radiosurgery. One patient with a partial response had neck node recurrence
      develop. Temporal lobe necrosis occurred in one patient but probably represents
      sequelae of primary radiation after reviewing the dosimetry. Ten patients are
      still alive, whereas one patient with local relapse had distant metastases
      develop and died. The estimated 1-year local control rate after radiosurgery was
      82%. CONCLUSIONS: Our preliminary results indicate that stereotactic radiosurgery
      is an effective treatment modality for persistent and recurrent T1-T2 NPC, and
      early control rate seems to be comparable to other salvage treatments. More
      clinical experiences and longer follow-up are still needed to validate our
      results and to address fully the role of radiosurgery in salvaging local failures
      of NPC.

PMID- 11505492
TI  - Feasibility and long-term results of autologous PBSC transplantation in recurrent
      undifferentiated nasopharyngeal carcinoma.
AB  - BACKGROUND: Recurrent undifferentiated nasopharyngeal carcinoma (UNPC) is a
      chemosensitive illness. Here we report long-term results of high-dose
      chemotherapy (HDC) as late intensification, with autologous peripheral blood stem
      cell (PBSC) support. METHODS: Six patients (5 men, 1 woman; median age 41years;
      median ECOG PS = 0) with recurrent UNPC (local, 2; local + nodal, 2; bone
      metastasis, 2) have been enrolled. All patients had been previously treated with
      neoadjuvant chemotherapy and radiotherapy; 3 of 4 local relapses had received a
      re-irradiation. Every patient received three courses of cisplatin + epirubicin
      and 1 cycle of epirubicin followed by PBSC collection. A median of 7.2 x 10(6)/kg
      (range, 4.5-18) CD34+ cells were reinfused. HDC was according ICE scheme:
      ifosfamide, 2.5 g/m(2)/d, + carboplatin, 300 mg/m(2)/d, + VP-16, 300 mg/m(2)/d
      days 1 through 4. RESULTS: After conventional chemotherapy, we had 1 CR (16%), 3
      PR (50%), and 2 NC (34%). After HDC, we had 4 CR (66%),1 PR (17%), and 1 MR
      (17%). Toxicity was manageable. After a median follow-up of 30 months (range, 14
      50), two patients are alive without disease (34%), one is alive with bone disease
      (16%), and three (50%) died of disease at 16, 18, and 24 months. CONCLUSIONS: HDC
      has an acceptable toxicity, can convert PR in CR, and seems effective, with long
      lasting CRs.

PMID- 11505493
TI  - Functional neck dissection: Fact and fiction.

PMID- 11505494
TI  - Two cases of primary malignant melanoma of the lacrimal sac.
AB  - BACKGROUND: Malignancy of the lacrimal sac is rare, and primary malignant
      melanoma in this region is extremely rare. METHODS: We report two cases of
      malignant melanoma of the lacrimal sac presented with epiphora and a palpable
      mass in the medial canthal area. We performed radical surgery and radiation
      therapy. RESULTS: The light microscopic, immunohistochemical, and electron
      microscopic studies confirmed the diagnosis. One of the patients, a 65-year-old
      woman, has no evidence of recurrence or distant metastasis 3 years after surgery
      and radiotherapy, whereas another patient, a 56-year-old man, died of distant
      metastasis 6 months after surgery and radiotherapy. CONCLUSIONS: We present two
      cases of malignant melanoma of the lacrimal sac that masqueraded as chronic
      dacryocystitis. Head and neck surgeons should be aware of this disease entity
      when encountered with patients with epiphora and mass in the medial canthal area.

PMID- 11505496
TI  - [The medical team approach to the suicide--attempted patients by taking drugs or
      chemicals--participation of the medical social workers].
AB  - There are many suicide-attempted patients admitted to the critical care medical
      center of the Kitakyushu General Hospital. Suicide-attempted patients need
      psychosocial intervention from the beginning of their hospitalization, because
      they have their own psychosocial problems. Accordingly, medical social workers
      (MSW) give psychosocial assistance to the patients in our critical care medical
      center. In 1997, we participated in the treatment of 53 patients out of 64
      suicide-attempted patients. Forty-four patients committed suicide by ingesting
      some drugs or poisons, and 9 patients committed suicide by jumping from a height
      or by self-burning. Kinds of drugs or chemicals used for suicide were medicinal
      drugs (55.3%), household medicines (14.9%), agricultural chemicals (10.7%),
      insecticides (8.5%), detergents (4.3%), household chemicals (4.3%) and others
      (2.0%). The largest number of male patients was in their fifties (6 out of 15
      male patients). Patients with alcoholism held the first place in male patients.
      The largest number of female patients was in their twenties (11 out of 29 female
      patients). There were many female patients with mood disorder, drug dependence or
      psychopathy. If the patients are discharged without receiving psychosocial
      measures, it may be every possibility that the patients commit suicide again. MSW
      make the cause of suicide clear and assess the mental status, and also have
      interview with patient's families. If both MSW and the doctors in charge judge
      that there is high possibility of repeated suicide, MSW introduce the patient to
      the special hospital under the consent of the patient and families. Thirty-five
      patients out of 44 patients transferred to the psychiatric hospitals. It is
      important that MSW join the treatment of suicide-attempted patients in order to
      prevent repeated suicide.

PMID- 11505497
TI  - [Determination of 4-O-methylpyridoxine (MPN) by HPLC with diode-array detector].
AB  - We have developed a simple and rapid method for measuring 4-O-methylpyridoxine
      (MPN) in the serum of an acute poisoning patient by high-performance liquid
      chromatograph (HPLC) with a diode-array detector. MPN, a poisonous ingredient of
      ginkgo seeds was extracted using an Isolute C18 solid-phase extraction column.
      Equal volumes of the extract were injected into a C18 HPLC column using
      acetonitrile-10 mM phosphate buffer (pH 3) as the mobile phase. Excellent
      linearity was obtained over the range of 1-1000 ng at a wavelength of 290 nm, and
      its detection limit of approximately 0.5 ng was considered to be satisfactory.
      The mean recovery of MPN in the serum was 92.9 +/- 6.1%. The method was used
      successfully in a case of acute poisoning.

PMID- 11505498
TI  - [Gut decontamination--3--Gastrolavage].

PMID- 11505499
TI  - [Re-evaluation of surgical indication to lung cancer].

PMID- 11505500
TI  - [Controversy over the UICC-TNM classification].
AB  - The new UICC-TNM classification is accepted by most thoracic surgeons and medical
      oncologists because the prognosis of lung cancer patients is well distinguished
      by stage based on the TNM classification. However, there are several
      controversies over improving the classification. The number of small-sized
      peripheral lung cancers detected by helical computed tomography screening is
      rapidly increasing in Japan. The prognosis for patients with these tiny lung
      cancers is extremely good. Therefore, these lung cancers should be separated from
      T1 lung cancers detected by conventional chest X-ray. T2 includes a wide range of
      tumor sizes. The prognosis of T3 disease is different depending on the organs
      invaded. T4 disease is a contraindication for surgery, although some T4 cases
      could undergo complete resection and be cured. T4 disease should therefore be
      divided into operable T4 and inoperable T4. The most important controversy over
      the N factor is the boundary between N1 and N2 because of the lack of a
      universally common map of lymph node stations. Classification of satellite
      nodules is another controversy. Most proposals by Japanese surgeons are based on
      postoperative pathological TNM classification and staging. Pathological
      classification indicates postoperative prognosis well. Prognostic analysis based
      on clinical classification indicates postoperative prognosis well. Prognostic
      analysis based on clinical classification is needed to determine the strategy for
      each patient.

PMID- 11505501
TI  - [Surgery for non-small cell lung cancer based on the T factor].
AB  - We review the indications of surgery in patients with non-small cell lung cancer
      (NSCLC) based on the T factor, focusing on peripheral small tumors, invasion to
      other organs, and the presence of malignant pleural effusion or intrapulmonary
      metastasis. While limited surgery in patients with peripheral, small-sized NSCLC
      preserves postoperative pulmonary function, the prospects for long-term survival
      are reduced due to the likelihood of recurrence, Novel prospective studies are
      being conducted to determine the indications for limited surgery in such patients
      which focus on histology, tumor size, and pulmonary function. In some patients
      with locally advanced disease, especially with invasion of the chest wall (T3),
      pericardium (T3), left atrium (T4), great vessel (T4), and carina (T4) and with
      malignant pleural effusion found intraoperatively and ipsilateral intrapulmonary
      metastasis, complete resection results in long-term survival. Thus surgery should
      be considered in patients without N2 disease.

PMID- 11505502
TI  - [Reevaluation of the surgical indications for lung cancer based on the N factor].
AB  - The Standard surgical treatment for stage I, II, and IIIa non-small cell lung
      cancer (NSCLC) is lobectomy with systemic mediastinal lymph node dissection. More
      than 50% of our series of 220 patients with cN2 disease were classified as pN0-1.
      The postoperative 5-year survival rate of patients with cN2 disease was 36%, and
      that of those with cN2-pN2 disease was 18%. Tumor cell type, surgical technique,
      or site of tumor had no prognostic significance, although pN, cT, and number of
      N2 sites were of prognostic significance. We conclude that the indications for
      surgery are T1-2 N2 disease with a single N2 site.

PMID- 11505503
TI  - [Surgical indications for lung cancer: influence of the M factor].
AB  - The presence of distant metastasis indicates systemic dissemination of disease.
      Patients with lung cancer in this category are not usually considered candidates
      for surgical resection of the primary and metastatic sites, although newly
      emerging treatment modalities for lung cancer improve survival. We need to
      conduct clinical trials in patients with distant metastases. We conducted a
      retrospective analysis of the surgical outcome of 16 PM2 patients who are now
      classified as having M1 disease. The 3-16 year survival rate was 45% and 5-year
      survival rate 14% in our facility. Among the 11 patients had N2 disease and a
      poor prognosis. Long-term survival can be achieved if the histology shows low
      grade malignancy and there is no lymph node involvement (N0 status). Patients
      with solitary brain metastasis also have a poor outcome even after surgical
      resection of both the brain metastasis and primary lung cancer. In this group,
      surgical intervention should be restricted to those in whom the quality of life
      is expected to improve, since it has been reported that no improvement in
      survival can be expected. We should investigate which patient groups can achieve
      long-term survival when surgically treated. The TNM classification had better be
      revised so that patients who benefit from simultaneous lung and metastatic
      resection are classified in earlier-stage groups.

PMID- 11505504
TI  - [Wedge resection for lung cancer].
AB  - The role of wedge resection in lung cancer is reviewed. In the past century, many
      reports appeared dealing with limited resection for lung cancer, and it is clear
      that wedge resection should be performed in patients who are considered at high
      risk for not tolerating lobectomy; still there is no prospective or even
      retrospective study on wedge resection carried out in candidates for lobectomy.
      In recent years, progress in imaging diagnostic technology using high-resolution
      computed tomography has increased the opportunity to diagnose early
      adenocarcinoma presenting as small ground-glass opacity (GGO) which could not be
      detected on chest radiographs. Some patients with GGO may become candidates for
      wedge resection in this century, if additional favorable data result from
      prospective studies relevant to imaging diagnosis, pathology, and prognosis.

PMID- 11505505
TI  - [Video-assisted thoracoscopic surgery lobectomy for lung carcinoma].
AB  - Video-assisted thoracoscopic surgery (VATS) has been utilized worldwide for the
      treatment of various types of thoracic disease, in particular for lung carcinoma.
      The following criteria are accepted as the operative indications for VATS
      lobectomy: i) clinical T1N1M0: ii) tumor located in the peripheral zone; and iii)
      non-small cell carcinoma. Videoscopic surgery has the merit of being less
      invasive, resulting in a low level of postoperative chest pain, short incisional
      scar, and short duration of hospital stay. Right-side upper mediastinal lymph
      node dissection is easy under the thoracoscope, although compared with standard
      thoracotomy it is not always possible to perform complete level II dissection on
      the left, because of the difficult approach to lymph nodess No. 3 and No. 4 under
      the aortic arch via the thoracoscope. The postoperative 5-year survival rate
      after VATS lobectomy is superior to that after standard thoracotomy. It is
      expected that the indications for VATS will be expanded to include T2 or N1
      disease as thorascopic instruments and techniques improve.

PMID- 11505506
TI  - [Reevaluation of bronchoplasty for central-type lung cancer].
AB  - The outcome, anastomotic complications, and recurrence rate after bronchoplasty
      carried out in 198 patients with bronchogenic carcinoma in our institutions were
      evaluated retrospectively. The outcome of bronchoplasty was reasonable (5-year
      survival rate of 58%), but that of patients with adenocarcinoma was poor (5-year
      survival rate of 13%) because of their advanced stage and less complete
      resection. The complications of anastomosis occurred in 8.2% after bronchoplasty.
      Postoperative pneumonia significantly increased the risk of complications. There
      was no difference in the incidence of complications between patients who received
      end-to-end and telescope-type anastomosis. Local recurrence at the anastomosis
      occurred in 4.9% who underwent bronchoplasty, but in 28% who underwent carinal
      resection. Lymph node metastasis was a risk factor for local recurrence. Twenty
      patients with early superficial squamous cell carcinoma in the central bronchus
      were treated with photodynamic therapy without local recurrence. This new
      modality may be of benefit to selected patients.

PMID- 11505507
TI  - [Preoperative induction therapy in non-small cell lung cancer].
AB  - The clinical significance of preoperative induction therapy for non-small cell
      lung cancer (NSCLC) is reviewed. As the survival rate in locally advanced NSCLC
      patients remains poor, preoperative therapy has been attempted in order to
      improve survival. Whereas some prospective phase II and phase III studies have
      demonstrated that preoperative cisplatin-based chemotherapy with or without
      concurrent radiation may improve the prognosis, the efficacy has not been
      established. Recently, some new chemotherapeutic agents such as paclitaxel and
      gemcitabine have been introduced, and it has been suggested that preoperative
      therapy using these new drugs may be more effective. To establish effective
      preoperative therapy regimens, more sophisticated, prospective, randomized
      studies in sufficient numbers of homogenous populations such as mediastinoscopy
      proven stage IIIA, T1-2N2 patients should be conducted.

PMID- 11505508
TI  - [Reevaluation of the surgical indications for non-small cell lung cancer based on
      the results of postoperative treatment].
AB  - Patients who undergo complete surgical resection for pathological stage I-IIIa
      non-small cell lung cancer (NSCLC) are candidates for postoperative chemo- and/or
      radiotherapy. The indications for surgical resection are not a problematic issue,
      regardless of the results of postoperative therapy. So far there have been no
      definitively positive results in randomized phase III trials comparing
      postoperative adjuvant therapy with no further therapy. Therefore clinical trials
      should be conducted to determine the most appropriate postoperative regimen in
      NSCLC.

PMID- 11505509
TI  - [Notification of unexpected patients' death to the police].
AB  - Controversies continue to exist in what situation the surgeons are obliged to
      report the perioperative patients' death to the police. With regard to this
      issue, Japan Surgical Society and twelve other Japanese Surgical Societies have
      declared that 1) patients' death due to evident malpractice must be reported to
      the police, 2) patients' death resulting from anticipated surgical complications
      need not be reported to the police, 3) an independent organization be founded for
      collection and investigation of medical accident/incident reports. Japan Surgical
      Society will take a responsibility of making a practical guideline as to the
      notification of accidents to the police and take a leadership in establishing the
      independent medical accident/incident center.

PMID- 11505510
TI  - ["Unusual death" in relation to the clinical practice].
AB  - Japan Surgical Society has made a declaration about patients' "unusual death"
      which incidentally occurred in their clinical courses, in reference to the
      practitioners' duty to notify the police under Article 21 of the Medical Act. The
      meanings of this declaration could be summarized in three points. Firstly, it
      confirms opportunities to reveal evident medical malpractices causing patients'
      deaths by affirming the duty in the cases it is suspected that patients' deaths
      were caused by evident medical malpractices. Secondly, it requires impartial
      inquiries to judge negligence about anticipated complications after surgery by
      denying the duty in the cases that patients died as results of anticipated
      complications after surgery. Thirdly, it proposed establishment of a generalized
      system to be noticed about medical malpractices causing patients' injuries
      irrespective of causing patients' deaths and to collect data concerning small
      incidents and risks in medical practice. The society would start to make a
      detailed guideline of "unusual death" in relation to the clinical practice.
      However, such a guideline should be made as an applicable one for that of the
      malpractices which practitioners are obliged to report under the generalized
      system.

PMID- 11505511
TI  - [The mind and the disorders].

PMID- 11505512
TI  - [Dynamics of interleukin (IL)-18 in serum, synovial fluid and synovial membrane
      in the patients with rheumatoid arthritis].
AB  - OBJECTIVES: IL-18 is a novel cytokine that plays an important role in the Th1
      response. The aim of this study is to investigate the dynamics of IL-18 in serum,
      synovial fluid and synovial membrane in the patients with rheumatoid arthritis.
      MATERIALS AND METHODS: The serum, synovial fluid and synovial membrane were
      obtained from RA patients at operation. The levels of IL-18 in the serum and
      synovial fluid were measured by ELISA. We then examined the expression of IL-18
      in synovial tissues using anti-human IL-18 monoclonal antibody in
      immunohistochemical study. RESULTS: The levels of IL-18 in serum and synovial
      fluid in RA patients were 193.7 +/- 109.7 pg/ml and 258.8 +/- 238.0 pg/ml,
      respectively. Compared with OA patients and normal volunteers, the level of IL-18
      in RA patients was higher in both serum and synovial fluid. (P < 0.05) In
      synovial membrane, the cells positive for anti IL-18 antibody were confirmed not
      only in RA (n = 26) but also in OA (n = 7) patients. The positive cells were the
      synovial lining cells, macrophages, fibroblasts and endothelial cells. However, a
      large number of positive cells were demonstrated in synovial tissues in RA
      compared with OA patients.

PMID- 11505513
TI  - [Effect of actarit combination therapy in patients with active rheumatoid
      arthritis resistant to gold agents].
AB  - We investigated the utility of combination therapy of actarit with gold agents in
      patients with active rheumatoid arthritis resistant to gold agents even after the
      administration of gold agents for longer than 24 weeks in principle. 1. In the
      final global improvement rate by the combination therapy of actarit with gold
      agents, the ratio of "improved" and/or better was 30.8% (12/39). 2. The clinical
      evaluation items which showed significant improvement were grip strength, ESR,
      number of painful joints, number of swollen joints, active joint count, duration
      of morning stiffness and Lansbury's activity index. 3. ADRs were observed in 6
      patients per 75 patients (8.0%), but there was no serious ADR.

PMID- 11505514
TI  - [The clinical evaluation of the lateral wedged insole fixed elastically on the
      subtalar joint of patients with osteoarthritis of the knee].
AB  - We assessed the clinical efficacy of a lateral wedged insole with elastic
      fixation of the subtalar joint for conservative treatment of osteoarthritis of
      the knee. Novel insoles with elastic subtalar fixation (fixed insole) and a
      traditional shoe insert wedged insoles (inserted insole) were prepared. Seventy
      one new female outpatients with osteoarthritis of the knee (knee OA) were treated
      with wedged insoles for 3 months. Randomization was performed according to birth
      date. The Severity Index of Lequesne, et al at the final assessment was compared
      with that at baseline in both the inserted and fixed insole groups. There were 37
      participants in the inserted group and 34 participants in the fixed insole group.
      Regarding discomfort during nocturnal bed rest, 21 out of 34 (61%) participants
      were positive at the baseline assessment, however, only 8 out of 34 (27%) were
      positive at the final assessment in the fixed insole group (P = 0.033). In the
      fixed insole group, the number of participants complained immediate pain after
      walking was decreased from 28 (82%) at the baseline assessment to 17 (50%) at the
      final assessments (P = 0.0104). These significant differences were not found in
      the group with the inserted insole. Thus, clinical efficacy of lateral wedged
      insole may be emphasized with elastic fixation of the subtalar joint.

PMID- 11505515
TI  - [A case of dermatomyositis complicated with pneumomediastinum that was
      successfully treated with cyclosporin A].
AB  - We reported the case of a 39-year-old man with dermatomyositis (DM) complicated
      with subcutaneous emphysema and pneumomediastinum during steroid therapy. The
      patient had complained of muscle weakness, dyspnea and skin eruption on his
      anterior chest wall 6 months prior to admission. He was diagnosed as having DM on
      the basis of an elevation in myogenic enzymes, myogenic changes in
      electromyography, a skin biopsy and a muscle biopsy. Chest roentgenogram revealed
      interstitial pneumonia (IP) in the lower lobes of the lungs. The administration
      of prednisolone (60 mg/day) was initiated, which resulted in improvement of DM.
      Fifteen days after the initiation of the steroid therapy, the patient developed
      subcutaneous emphysema and pneumomediastinum. Additional administration of
      cyclosporin A (CsA) enabled us to rapidly taper the dose of prednisolone without
      aggravating the diseases. Several reports have shown that vasculitis might be
      involved in the pathogenesis of pneumomediastinum in DM patients. Infection and
      tissue fragility due to steroid therapy worsen the outcome of those patients. CsA
      therapy may improve the outcome through the anti-vasculitic- and steroid sparing
      effects.

PMID- 11505517
TI  - [Arthritis and ADAM family protease].

PMID- 11505516
TI  - [A case of recurrent hemophagocytic syndrome complicated with systemic sclerosis:
      relationship between disease activity and serum level of IL-18].
AB  - Hemophagocytic syndrome (HPS) is characterized by the activation of the
      mononuclear phagocytic system with prominent hemophagocytosis in the bone marrow
      and reticuloendothelial systems, and its occurrence is usually associated with
      variable disorders such as viral infections and malignant lymphoma. Recently, it
      was reported that HPS also occurred in association with underlying connective
      tissue disease, especially systemic lupus erythematosus. We report here a case of
      recurrent HPS complicated with systemic sclerosis. A 32-year-old woman had been
      diagnosed as systemic sclerosis since 1994. She was admitted due to unknown high
      fever and severe pancytopenia in 1997, and the diagnosis of HPS was determined
      because of hemophagocytosis in bone marrow and hyperferritinemia. Her symptoms
      were improved by immunosuppressive therapies including steroid pulse therapy and
      oral prednisolone (60 mg/day). She was followed by the treatment of oral
      prednisolone which was gradually tapered in our out-patient clinic. In August of
      1999 high fever and severe anemia were recurred, and she was admitted again to
      our hospital because of the diagnosis as recurrent HPS. She had been treated with
      40 mg/day of oral prednisolone and fever was immediately disappeared and
      hemoglobin was gradually increased. HPS is considered to be a rare complication
      with systemic sclerosis, and the etiology has been unknown. IL-18 is a novel
      cytokine which is a potent inducer of interferon-gamma, and its properties may be
      a proinflammatory regulation and activation of monocyte/macrophage and histiocyte
      through the expression of interferon-gamma. Therefore, the significance of IL-18
      in the pathophysiology of HPS was recently reported. In this case, we
      investigated the significance of IL-18 and revealed the levels of serum IL-18
      were well correlated with disease activity of HPS.

PMID- 11505518
TI  - [Changes in the clinical features and prognosis of collagen diseases and their
      contributing factors: 30 years of past progress and prospect for the 21st century
      in our department].

PMID- 11505519
TI  - [The present and the future of ex vivo expansion of hematopoietic stem cells].

PMID- 11505520
TI  - [How should patients with essential thrombocythemia be treated?].

PMID- 11505521
TI  - [Guideline for diagnosis and treatment of deep mycosis].

PMID- 11505522
TI  - [Characterization of Epstein-Barr virus-specific CD8+ T cells in infectious
      mononucleosis].

PMID- 11505523
TI  - [EBV and HHV-6 in lymphoproliferative diseases].

PMID- 11505524
TI  - [Use of lightcycler PCR to monitor viral infections in hematologic disorders].

PMID- 11505525
TI  - [Pathology of human herpesvirus 8 (HHV-8)].

PMID- 11505527
TI  - [Allogeneic bone marrow transplantation for refractory multiple myeloma: presence
      of a graft-versus-myeloma effect].
AB  - We investigated the graft-versus-myeloma effect (GVM) after allogeneic bone
      marrow transplantation (allo-BMT). Three patients with refractory multiple
      myeloma (MM) underwent related allo-BMT. Two of the patients showed disappearance
      of serum M protein 4 and 5 months after transplantation, respectively. One of
      them has remained in complete remission for more than 22 months after allo-BMT,
      with accompanying chronic GVHD. Two patients with relapse and disease progression
      after allo-BMT underwent donor lymphocyte infusion (DLI). Although one patient
      did not respond to DLI, the other developed acute GVHD after 4 weeks and achieved
      a 75% reduction in serum M protein. DLI did not produce severe acute GVHD or
      myelosuppression. These findings suggest the presence of a GVM effect. DLI may be
      an effective therapy for patients with MM who have relapsed after allo-BMT.
      Furthermore, non-myeloablative stem cell transplantation (mini-transplantation)
      for refractory MM should be investigated further as a potentially curative
      option.

PMID- 11505526
TI  - [Light and shade on the treatment of HIV infection].

PMID- 11505528
TI  - [Analysis of chimerism in patients with hematologic malignancies after allogeneic
      hematopoietic stem cell transplantation].
AB  - Serial monitoring of chimerism after allogeneic hematopoietic stem cell
      transplantation (HSCT) can be performed easily and rapidly using PCR-based assays
      analyzing informative tandem repeat genetic markers. Sequential analysis of
      individual chimerism status was performed in 34 patients who underwent
      myeloablative allo-HSCT using a commercial multiplex short tandem repeat (STR)
      kit. Mixed chimerism (MC) was found in 14 of the patients for more than one
      month. The incidence of MC seemed to be dependent on the type of disease or
      pretransplantation regimen. There was no significant difference in relapse rates
      between MC and complete donor chimerism (CC) in all patients. However, the
      relapse rate was significantly higher in MC than in CC among patients with acute
      leukemia. The severity of acute graft-versus-host disease (aGVHD) was
      significantly reduced in the patients with MC. Most of the MC patients with
      hematologic malignancies had transient mixed T-lymphoid chimerism, and CC was
      achieved within 6 months after HSCT in such cases. Patients with MC beyond 6
      months after HSCT and patients with reappearance of autologous signals (MC after
      CC) may have an enhanced risk of relapse.

PMID- 11505529
TI  - [Secondary eosinophilia in a patient with hypereosinophilic syndrome after
      allogeneic bone marrow transplantation from a sibling donor].
AB  - A 23-year-old man first visited a local hospital in 1998 because of exertional
      dyspnea. Peripheral blood examination revealed mild leukocytosis with 82%
      eosinophils, and he was treated with prednisolone. As the eosinophilia did not
      improve, he was referred to Tokai University Hospital in March 1999 for further
      diagnosis and treatment. The patient was diagnosed as having hypereosinophilic
      syndrome (HES) because of unexplained hypereosinophilia persisting for more than
      6 months, resulting in cardiac dysfunction. His disease was progressive in spite
      of immunosuppressive therapy, interferon-alpha and cytotoxic chemotherapy. Since
      he had an HLA-identical brother, allogeneic bone marrow transplantation (BMT) was
      performed in October 1999. After completion of the immunosuppressive therapy on
      day 79 after BMT, the number of eosinophils gradually increased again. Although
      we suspected recurrence of the disease, DNA fingerprinting revealed that the
      peripheral granulocytes were 100% donor type. An increase of interleukin-5 (IL-5)
      produced by peripheral lymphocytes and a decrease of the Th1/2 ratio suggested
      that the eosinophilia was related to GVHD. The eosinophilia was eventually
      controlled by cyclosporin. We conclude that DNA fingerprinting and examination of
      the IL-5 level and Th1/2 ratio are useful for differentiating between relapse and
      GVHD in cases of eosinophilia occurring after BMT for HES.

PMID- 11505531
TI  - [Severe thrombocytopenia induced by radiographic non-ionic contrast medium].
AB  - A 70-year-old man was admitted to our hospital because of right hemiparesis. He
      had no allergies or previous exposure to radiographic contrast medium, and the
      platelet count on admission was within the normal range. On day 8 of
      hospitalization, he underwent computed tomography of the brain with 100 ml of
      iopamidol administered intravenously. Three hours later, his platelet count fell
      to 5,000/microliter, and he developed purpura. Because drug-induced
      thrombocytopenia was suspected, platelet transfusion was undertaken and
      corticosteroids were administered. The platelet count returned gradually to
      normal in 2 days. At the time, we were unable to ascertain the cause of the
      thrombocytopenia. To clarify whether the contrast medium had been responsible,
      iopamidol was added to the patient's heparinized whole blood. Subsequent platelet
      aggregation was observed microscopically and the platelet count decreased,
      suggesting that the thrombocytopenia had been due to contrast medium-induced
      platelet aggregation. Although thrombocytopenia after injection of contrast
      medium is extremely rare, such cases should be evaluated carefully because the
      condition can be life-threatening if severe.

PMID- 11505530
TI  - [AML(M7) associated with t(16;21)(p11;q22) showing relapse after unrelated bone
      marrow transplantation and disappearance of TLS/FUS-ERG mRNA].
AB  - A 3-year-old boy with poorly prognostic acute megakaryoblastic leukemia (AML M7)
      showing t(16;21)(p11;q22) karyotype underwent unrelated bone marrow
      transplantation (U-BMT) during his first hematological remission. The
      conditioning regimen consisted of BU, VP-16 and L-PAM. Engraftment was smooth,
      but the patient developed grade I acute GVHD. During hematological remission
      before U-BMT, the TLS/FUS-ERG chimeric transcript of t(16;21)(p11;q22) was
      consistently detectable as minimal residual disease (MRD) by RT-PCR. However,
      after U-BMT it soon became undetectable. There was no detectable MRD until 7
      months after U-BMT, but bone marrow relapse occurred 10 months after U-BMT. We
      consider that U-BMT is a promising treatment for t(16;21)(p11;q22) AML. However,
      an intensified conditioning regimen or modification of GVHD prophylaxis is
      needed.

PMID- 11505532
TI  - [Diffuse large B-cell lymphoma expressing cytoplasmic IgM and kappa in a patient
      with lambda-type primary macroglobulinemia].
AB  - A 69-year-old woman who had had lambda-type primary macroglobulinemia (PMG) since
      December 1993 was admitted in October 1997 because of obstructive jaundice due to
      compression of the common bile duct by a retroperitoneal tumor. A biopsy sample
      was obtained by exploratory laparotomy, and from this a diagnosis of diffuse
      large cell lymphoma (DLCL) expressing cytoplasmic IgM/kappa was made. Partial
      remission was obtained after 6 courses of combination chemotherapy consisting of
      pirarubicin, cyclophosphamide, vincristine and prednisolone. However, the DLCL
      was generally progressive, and the patient died in August 1998 due to multiple
      organ failure. There was no difference in the plasma monoclonal IgM/lambda level
      before and during the course of DLCL. The clone of the DLCL may have been
      different from that of the PMG.

PMID- 11505533
TI  - [Usage of the novel synthetic material carbilan for urinary tract reconstruction
      in experiment].
AB  - Carbilan was tried as a new synthetic suturing material and ureteral prosthesis
      in reconstruction surgery on the urinary tracts. In experiments on 24 dogs
      carbilan suturing threads were used for establishment of ureteral-ureteral and
      vesicoureteral anastomoses, suturing of the ureter, bladder or urethra. In a
      comparative group of 36 dogs such operations were made using chrome-plated
      catgut. Complications occurred in 3.8 and 17.6% of the dogs from the carbilan and
      catgut groups, respectively. Replacement of the part of the ureter in the middle
      or in the lower third 3-5 cm in length for a carbilan transplant was conducted in
      8 dogs. In 6 cases of the suture leaking, the prosthesis underwent deformation
      and compression by commissures which formed around the flap within 3 months after
      the implantation. In 2 experiments the prosthesis was sealed with fibrin (a short
      term implantation into the artery). This provided normal function of the
      prosthesis for 9-13 months. Later, the urinary tracts were also obstructed. No
      occlusions of the prosthesis with urinary salts or detritus were observed.
      Histologically, both suturing threads and ureteral prosthesis made of carbilan
      showed good biocompatibility. Massive commissures around the prosthesis arose
      because of its leaking and contact of the urine with the surrounding tissues.

PMID- 11505534
TI  - [Doksazozin "Cardura" in acute urinary retention caused by benign prostatic
      hyperplasia].
AB  - Drug treatment of acute ischuria (AI) caused by benign prostatic hyperplasia
      (BPH) is discussed. Catheterization of the urinary bladder is the main treatment
      for AI. AI is caused by anatomical obstruction, hypertone of smooth myocytes, and
      energy imbalance of detrusor. Use of alpha 1-adrenoblockers in AI is
      pathogenetically justified, as the development of stable spasm of smooth-muscle
      structures of the prostate, vesical cervix, and prostatic compartment of the
      urethra resultant from increased functional activity of alpha 1-adrenoreceptors
      underlies the dynamic component of obstruction. alpha 1-Adrenoblocker doxazosin
      (cardura) was used for arresting AI caused by BPH after 12-h randomization and
      catheterization of the bladder. A prospective randomized placebo-controlled study
      was carried out on 36 patients. Spontaneous urination was restored in 55.5%
      patients, in 63.3% of these after doxazosin and in 16.6% after placebo. 37.9% of
      patients from the doxazosin group were discharged from hospital for outpatient
      therapy with alpha-blockers and the rest were operated on. Hence, doxazosin
      increases the chance of recovery of spontaneous urination for patients with AI
      caused by BPH and allows time and conditions for preparation of patients to
      surgery. Therapy with alpha 1-adrenoblockers after resolution of AI in patients
      with BPH can be effective and should be further investigated.

PMID- 11505536
TI  - [Alpha-adrenergic inhibitors (dalphase) in bladder reservoir dysfunction].

PMID- 11505535
TI  - [Finasteride in prolonged therapy of patients with benign prostatic hyperplasia].
AB  - The efficiency of finasteride alone and in combination with alpha 1-adrenoblocker
      tamsulasine in long (2-4 years) treatment of benign prostatic hyperplasia is
      analyzed, based on published reports and the author's data. Specific features of
      long finasteride therapy are discussed: decrease in the level of prostatic
      specific antigen, no effect in case of concomitant infectious chronic
      prostatitis, more stable result in combination with tamsulasine, higher
      efficiency of finasteride after a previous course of therapy for prostatitis.
      Indications for finasteride therapy are defied. The results of finasteride
      therapy directly correlate with the size of the prostate in 78% patients.

PMID- 11505537
TI  - [Bicalutamide monotherapy of patients with disseminated forms of prostatic
      cancer].
AB  - Combined antiandrogen therapy (complete androgen blocking) implies surgical or
      chemical castration in combination with antiandrogen therapy. Both sources of
      androgens are thus blocked in patients with locally disseminated prostatic
      cancer. The purpose of this study was to evaluate the efficiency of bikalutamide
      (150 mg) monotherapy. The study was carried out in 58 patients with prostatic
      cancer (stages T3-T4) divided into 2 groups: 1) bikalutamide monotherapy (150 mg
      daily) and 2) bikalutamide (50 mg daily) + bilateral orchidectomy. All patients
      were examined before and 3, 6, 12, 18, and 24 months after the beginning of
      therapy. The efficiency of non-steroid antiandrogen was higher in group 1. The
      mean level of prostate-specific antigen in this group decreased to 10.6 ng/ml by
      24 months, while in group 2 to 25.3 ng/ml. Hence, bicalutamide was effective,
      safe, and well tolerated in our study, and is therefore recommended as
      monotherapy for patients with disseminated forms of prostatic cancer.

PMID- 11505538
TI  - [Doppler ultrasonography of penile vessels in combination with various methods of
      erectile stimulation in diagnosis of erectile dysfunction].
AB  - Ultrasonic dopplerographic investigation (Ultramark-9, USA) was made in 227
      males. 50 males with normal erection served controls. Stimulation of erection
      with an individual LOD-device is a low-invasive, convenient to standardize
      technique in ultrasonic dopplerographic examination of penile vessels for
      diagnosis of erectile dysfunction. Erection stimulation by different methods in
      the same patient during penile vessel dopplerography raises diagnostic value of
      this method.

PMID- 11505539
TI  - [Acute scrotum: clinical picture, diagnosis, treatment].
AB  - The purpose of this study was to evaluate the potentialities of ultrasonic
      dopplerography and radioisotope scanning of the scrotal organs for the diagnosis
      of acute scrotal diseases and defining the indications to surgery in patients
      with acute epididymoorchitis. A total of 128 subjects were examined (23 healthy
      controls and 105 patients with scrotal diseases). 139 ultrasonic and 76
      radioisotope scannings of the scrotum were carried out. Ultrasonic scanning plays
      the key role in the diagnosis of traumatic and inflammatory epididymoorchitis.
      Radioisotope study is more informative in the diagnosis of torsion of the
      testicle. The data indicate high informative value of ultrasonic and radioisotope
      studies in differential diagnosis of acute scrotal diseases and diseases
      simulating an acute process in the testicle and appendage. A positive feature of
      both methods is the possibility of their repeated use for evaluating the
      treatment efficiency. Analysis of 241 cases with acute epididymoorchitis showed
      that early surgical treatment of patients with pyodestructive inflammation
      promotes rapid recovery. Ultrasonic monitoring helps timely detect the
      complications and correct the treatment strategy. Wide use of ultrasonic and
      radioisotope methods of examination in patients with acute scrotal diseases
      promote timely detection of pathological changes and better results of treatment.

PMID- 11505540
TI  - [Harmful effects of electrocorporal shock-wave lithotripsy].
AB  - Negative effects of extracorporeal shock-wave lithotripsy (ECSWL) were analysed
      in 101 patients aged 20 to 72 years. Urinary hemoglobin rise was found in all the
      patients. Protein levels rose if the calculi were located in the kidneys and low
      ureter. A 5-fold rise in plasma free hemoglobin in any position of the concrement
      indicates intravascular hemolysis as ECSWL hazards. Thus, ECSWL seems to damage
      stone-adjacent tissues and induce a general hematological reaction.

PMID- 11505541
TI  - [Vilprafene (josamycin) therapy of chronic chlamydial prostatitis].
AB  - Vilprafene was used in multiple-modality (immuno-, enzyme, spa, and local
      therapy) treatment of 15 patients with chronic chlamydial prostatitis. Clinical
      and etiological cure was attained in all patients without side effects.

PMID- 11505542
TI  - [Sacral anesthesia in transurethral resection of the prostate].
AB  - Block anesthesia has some advantages in transurethral surgery over general
      anesthesia. 48 patients were operated under sacral anesthesia and 47 patients
      under peridural anesthesia. Anesthesia-induced complications were compared to
      those published in the literature. It was found that in transurethral prostatic
      resection sacral anesthesia is more simple and cost-effective than peridural
      anesthesia.

PMID- 11505543
TI  - [Surgical correction of hydronephrosis in the retrocaval ureter].
AB  - The authors operated on 2 patients aged 12 and 13 years who had hydronephrosis
      and retrocaval ureter. Ureteropelvic segment resection with anastomotic plastic
      repair were antecavally made by the Anderson-Hynes-Kucera procedure in both
      patients. Good results were obtained. The follow-ups lasted 1 and 3 years.
      Histological studies of the ureteropelvic segments resected revealed structural
      changes in the wall, they were mainly of inborn genesis. The signs of
      malformations were ureteral wall sclerosis mainly located in the tunica
      submucosa; impaired myoarchitectonics as hypoplasia and disorganized muscle
      fascicles. The amount of agrophilic and elastic fibers was decreased. The
      findings led to the conclusion that the cause of hydronephrosis in the retrocaval
      ureter is ureteral wall structural abnormalities mainly of inborn genesis rather
      than the abnormal position of the ureter. These data show it necessary to resect
      the destructively changed segment to form a pyeloureteral anastomosis by using
      morphofunctionally normal tissues. The good outcomes of surgical correction of
      hydronephrosis with antecaval transposition of the anastomosis provide evidence
      for its pathogenetic rationale.

PMID- 11505544
TI  - [Creation of artificial urinary bladder in children].
AB  - In children creation of artificial urinary bladder using intestinal segments was
      made in the absent or reduced reservoir function of the bladder. From 1990 to
      1998 enterocystoplasty was performed in 30 boys and 6 girls. 15 of them have
      undergone colocystoplasty, 21--ileocystoplasty with detubulized segment. Holding
      conduits were made of the appendix or intestinal segment in 31 patients. On
      postoperative day 1-16 six patients developed complications demanding emergency
      operation--3 cases of comissural ileus and 3 of urinary peritonitis. 33 patients
      were followed up for 1 to 9 years. 29 patients urinated only through catheter 3
      to 6 times a day. 4 patients urinated without a catheter but they had imperative
      enuresis. Concrements in the artificial bladder were detected in 8
      postcolocystoplasty patients and 1 postileocystoplasty patient. The preference
      was given to ileocystoplasty with detubulized segment with creation of the
      holding conduit and occlusion of the bladder neck. The ileal artificial bladder
      is characterized by less probable long-term complications, greater volume, low
      pressure at filling, less intensive mucus production.

PMID- 11505545
TI  - [Bladder foreign body in a 4-year-old girl].
AB  - The specific feature of this case presented is the prolonged clinical
      manifestations of cystitis despite long-term and diversified antibacterial
      therapy. Repeated ultrasonography was justifiable in this cases since it could
      reveal a cause of protracted cystitis. Thus, in the young child long-term dysuria
      and urinary infection may be caused by a bladder foreign body.

PMID- 11505546
TI  - [Angioleiomyoma of the ureter].
AB  - Angioleiomyoma of the urinary excretory tract is an unusual, but benign
      condition. A case of pure angioleiomyoma of the ureter is reported. Renal tract
      ultrasonography showed hydronephrosis on the right side in a 15-year-old boy
      without urinary symptoms. Subsequent retrograde biopsy suggested leiomyoma.
      Nephrureterectomy was performed. Histologically, the removed specimen indicated
      ureteral angioleiomyoma. Difficulties in diagnosis and surgical treatment are
      discussed.

PMID- 11505547
TI  - [Papilloma of the seminal tubercle].

PMID- 11505548
TI  - [Endoscopic diagnosis and treatment of papillary tumors of the upper urinary
      tract].

PMID- 11505549
TI  - [2nd symposium: treatment of disseminated prostatic cancer].

PMID- 11505550
TI  - [Low-energy laser therapy in combined treatment of of patients with urinary
      tuberculosis].
AB  - 62 patients received polychemotherapy for tuberculosis of the kidney (control
      group) and 88 patients with the same diagnosis received the same polychemotherapy
      plus local laser therapy (study group). Efficiency of the treatment in the
      control group was 40.4 +/- 6.3%, in the study group--76.5 +/- 4.7%. Thus, the
      effect in the group with laser radiation was by 36.1% higher than in the
      controls. Indices of urinalysis, bacterial discharge and intoxication to the end
      of the hospital stay differed significantly (p < 0.05).

PMID- 11505551
TI  - Research misconduct.

PMID- 11505552
TI  - Current choices of sterilizing grade membrane filters available to the
      pharmaceutical industry.

PMID- 11505553
TI  - The compliance and science of Blend Uniformity Analysis.
AB  - According to 21CFR section 211.110(a) pharmaceutical manufacturers are legally
      required to demonstrate the adequacy of their mixing operations. The CFR,
      however, is intentionally silent on how this should be accomplished. The
      situation changed dramatically in 1993 as a consequence of The US vs. Barr
      Laboratories when Judge Alfred Wolin ruled for the government that the
      appropriate sample size for Blend Uniformity Analysis (BUA) is, at most, three
      times the weight of the final dosage unit. This ruling defined the Current Good
      Manufacturing Practices (cGMPs) for BUA in greater detail than is specified in
      21CFR section 211.110(a). It also established a precedent that has been the focus
      of an almost decade long controversy between pharmaceutical manufacturers and the
      FDA. At the heart of the matter is the inability of current sampling technology
      to consistently and reliably provide small representative samples from
      significantly larger static powder blends. The sample thief is the state-of-the
      art powder sampling technology used by the pharmaceutical industry today for
      purposes of BUA. Unfortunately, sample thieves are intrusive devices that are
      prone to sampling error. Sampling error can lead to powder samples that are not
      representative of the bulk blend from which they were collected. In general,
      sampling error increases as the concentration of the drug substance and the size
      of the sample decrease. Since Judge Wolin's ruling, sampling error has made it
      difficult, if not impossible, to validate the manufacturing processes for some
      acceptably uniform pharmaceutical products. This article reviews the compliance
      history of BUA as well as the associated scientific literature.

PMID- 11505554
TI  - In vitro hemolysis and buffer capacity studies with the novel marine anticancer
      agent kahalalide F and its reconstitution vehicle cremophor EL/ethanol.
AB  - An in vitro biocompatibility study was performed with the pharmaceutical
      formulation of the investigational, marine-derived anticancer agent kahalalide F
      developed for early clinical studies. The pharmaceutical formulation consists of
      a lyophilized product containing 150 micrograms kahalalide F, 3 mg citric acid, 3
      mg polysorbate 80, and 150 mg of sucrose per dosage unit, to be reconstituted
      with 3 mL of a mixture composed of Cremophor EL, ethanol, and water (5/5/90%
      v/v/v), resulting in a solution of pH 3 and to be further diluted in normal
      saline for infusion. The reconstituted product, infusion solutions, and
      Cremophor/ethanol (CE) vehicle were tested for hemolytic potential and buffer
      capacity. No significant hemolysis due to the kahalalide F formulation as well as
      the CE vehicle was found using both a static and dynamic test model. FB-ratio's
      (ratio of formulation solution (F) and volume of blood simulant (B) necessary to
      maintain physiological pH) as a measure of the buffer capacity of the kahalalide
      F infusion solutions examined indicated that no vascular irritation due to pH
      effects is expected in the intended administration schedule in the forthcoming
      Phase I study.

PMID- 11505555
TI  - Use of pilot plant facilities to aid validation programs.
AB  - According to the FDA guidelines (1), pilot plant facilities may be used to
      generate material to support process validation studies. The guidelines also
      state that process modifications are an inevitable part of process development
      and scale-up. However, if such modifications are made, there is a need to
      demonstrate that the products from both the old and new processes are comparable
      (2). Both of these guidelines were combined and applied during a recent
      development of a product at Genentech. In order to implement the process
      modifications and demonstrate product comparability, the pilot plant facilities
      were used for these production runs. As the process had changed and the product
      was being prepared for BLA submission, in process samples from the new
      manufacturing process were also required to support the process validation
      studies. By using pilot plant facilities to implement the process modifications,
      test product comparability, and produce material for process validation, we were
      able to minimize the impact of such work on the large-scale manufacturing
      facility.

PMID- 11505556
TI  - Reduction of risk and the evaluation of quality assurance.

PMID- 11505557
TI  - Novel colloidal drug delivery systems.

PMID- 11505558
TI  - Controlled release from an electrorheological fluid dosage form: experimental
      results for a prototype system.
AB  - A new controlled-release technology that is based on electrorheological fluids
      (ERF) is described, and a model system is investigated. Humidified starch
      (duration of humidification is 30-35 minutes) was used as a filler material
      (approximately 20% w/w) in olive oil to make the ER system, and benzocaine (BZN)
      was used as the model drug. The average particle size of starch in the olive oil
      was approximately 200 nm. 1N HCl was used as the receiver medium and BZN was
      assayed by UV spectroscopy at 226 nm. A series of studies was done at five
      temperatures (25 degrees, 30 degrees, 35 degrees, 40 degrees, and 45 degrees C)
      and two external electric fields (E-fields) that were generated by applying
      potential drops across the diffusion apparatus of 0 V and 290 V. Control studies
      of BZN release from olive oil without filler showed little or no increase in
      release rates resulting from application of E-fields. In addition, while
      reversing the polarity for BZN in olive oil caused differences in release rates,
      these differences were too small to explain the results obtained for the ER
      systems. It was found that release of BZN increased significantly with the
      application of the electric field (approximately 53% increase at 25 degrees C). A
      plot of the log of the release rate vs 1/T was linear for the 0 V data but
      deviated from linearity for the 290 V data. The increase in release rates due to
      the E-field became smaller as the temperature was increased. The results are
      consistent with (but are not sufficient to prove) the hypothesis that the
      increased release rate is due to a small amount of ordering of the cornstarch
      filler particles in response to the applied E-field, which results in a reduction
      in the tortuosity of the system.

PMID- 11505608
TI  - Learning complex sequences: no role for observation?
AB  - Two experiments examined performance in a sequence learning task. Participants
      were trained on a repeating sequence which was presented as a visual display and
      learning was measured via the increase in reaction time to respond to a new
      sequence. Some participants made a response to each stimulus while others merely
      observed the sequence. In Experiment 1 participants responding to the display via
      a keypress showed learning, but those merely observing did not. Five possible
      reasons for the failure to find observational learning were considered and the
      Experiment 2 attempted to resolve these. This second experiment confirmed the
      findings of Experiment 1 in a non-spatial sequence display using a cover story
      which encouraged attention to the display but not rule-search strategies. The
      results are discussed in relation to applied and theoretical aspects of implicit
      learning.

PMID- 11505585
TI  - Hormones in meat: different approaches in the EU and in the USA.
AB  - The use of hormonal active growth promoters ("hormones") in farm animals can
      increase the production of veal and beef significantly up to 15%. However, in the
      different parts of the world the regulation regarding the use of such hormones
      differs sharply. In the European Union there exists a total ban on such use in
      contrast to the United States of American where the use of some hormones is
      authorized under strict conditions. An overview is given of the different
      opposing aspects and their consequences are discussed. It has to be concluded
      that in some EU Member States an extended black market exists. For the USA no
      experimental evidence is available for such a black market. In the EU the number
      of ascertained different illegal "hormones" ranges between about 35 and 55. In
      the USA the number of legal hormones in total is six. The levels of hormone
      residues found in beef originating from the USA are in the fast majority of cases
      below the Maximum Residue Limit as recommended by the FAO/WHO Joint Expert
      Committee of Food Additives. No comparable experimental data are available for
      the EU. Finally other food commodities have to be taken into account to assess
      potential risks of the dietary intake of "hormones". Eggs, example given,
      contribute more to the dietary intake of estradiol than beef, whether the animal
      is legally treated with hormones or not.

PMID- 11505609
TI  - Negative priming from activation of counting and addition knowledge.
AB  - In two experiments, subjects were presented with digit pairs (e.g., 32) and asked
      to respond to the rightmost number. Negative priming, that is, slowed processing,
      was evident when the rightmost number was a counting-string (e.g., 43 following
      12) or addition-sum (e.g., 65 following 32) associate of the number pair from the
      preceding trial. The studies are the first to demonstrate negative priming with
      counting and arithmetical memory representations and suggest the obligatory
      activation of these representations with the presentation of number pairs. The
      results are also consistent with the view that negative priming often occurs at
      the semantic level.

PMID- 11505610
TI  - Do people combine the parity- and five-rule checking strategies in product
      verification?
AB  - The basic question of the present experiment was whether people use a combination
      of arithmetic problem solving strategies to reject false products to
      multiplication problems or whether they simply use the single most efficient
      strategy. People had to verify true and false, five and non-five arithmetic
      problems. Compared with no-rule violation problems, people were faster with (a)
      five problems that violated the five rule (i.e., N x 5 = number with 5 or 0 as
      the final digit; e.g., 15 x 4 = 62), (b) problems that violated the parity rule
      (i.e., to be true, a product must be even if either or both of its multipliers is
      even; otherwise, it must be odd; 4 x 38 = 149), and (c) problems that violated
      both the parity and five rules (e.g., 29 x 5 = 142). Finally, people were equally
      fast and accurate when they solved two-rule violation problems than when they
      solved five-rule violation problems, and faster for those two types of problems
      than for parity-rule violation problems. Clearly, people use the single most
      efficient strategy when they reject false product to multiplication problems.
      This result has implications for our understanding of strategy selection in both
      arithmetic in particular and human cognition in general.

PMID- 11505611
TI  - Motor learning enhances perceptual judgment: a case for action-perception
      transfer.
AB  - Transfer from perception to action is well documented, for instance in the form
      of observational learning. Transfer from action to perception, on the other hand,
      has not been researched. Such action-perception transfer (APT) is compatible with
      several learning theories and has been predicted within the framework of common
      coding of perceptual and motor events (Prinz, 1992, 1997). Our first experiment
      aimed at an empirical evaluation of APT and involved motor practice of timed two
      cycle arm movements on verbal command without visual feedback. In a transfer
      test, visual judgments of similar patterns had to be made. In addition, transfer
      from the visual to the motor task was studied. In Experiment 2 we separated
      kinesthetic aspects of motor practice from preparatory and efferent contributions
      to APT. The experiments provide evidence that transfer between perception and
      action is bi-directional. Transfer from perception to action and, more
      importantly, from action to perception was found. Furthermore, APT was equally
      pronounced for participants who had actively practiced movements during training
      and for passive participants who had received merely kinesthetic feedback about
      the movement. This kinesthetic-visual transfer is likely to be achieved via
      visuomotor-kinesthetic matching or via timekeeping mechanisms that are involved
      in both motor and visual performance.

PMID- 11505612
TI  - Human performance on visually presented Traveling Salesman problems.
AB  - Little research has been carried out on human performance in optimization
      problems, such as the Traveling Salesman problem (TSP). Studies by Polivanova
      (1974, Voprosy Psikhologii, 4, 41-51) and by MacGregor and Ormerod (1996,
      Perception & Psychophysics, 58, 527-539) suggest that: (1) the complexity of
      solutions to visually presented TSPs depends on the number of points on the
      convex hull; and (2) the perception of optimal structure is an innate tendency of
      the visual system, not subject to individual differences. Results are reported
      from two experiments. In the first, measures of the total length and completion
      speed of pathways, and a measure of path uncertainty were compared with optimal
      solutions produced by an elastic net algorithm and by several heuristic methods.
      Performance was also compared under instructions to draw the shortest or the most
      attractive pathway. In the second, various measures of performance were compared
      with scores on Raven's advanced progressive matrices (APM). The number of points
      on the convex hull did not determine the relative optimality of solutions,
      although both this factor and the total number of points influenced solution
      speed and path uncertainty. Subjects' solutions showed appreciable individual
      differences, which had a strong correlation with APM scores. The relation between
      perceptual organization and the process of solving visually presented TSPs is
      briefly discussed, as is the potential of optimization for providing a conceptual
      framework for the study of intelligence.

PMID- 11505613
TI  - Illusory smoke and dazzling fog.
AB  - It is well known that a flat ellipse rotating in the frontoparallel plane
      appears, after brief inspection, as a rigid circular disc tilting back and forth
      in a 3-D space. We here report that rotation of a grey-shaded ellipse on a white
      or on a black background produces the compelling illusion of a dark smoke or a
      dazzling fog (depending on the conditions of the background) moving in front of a
      completely white or completely black tilting disc. The fog effect disappears when
      there is a luminance contrast all along the perimeter of the ellipse. An
      experiment is reported showing that the effect can be experienced in static
      conditions only to a limited extent and mostly in the 'dazzling' version, and
      that relative movement between the contours of the figure and the shaded area is
      crucial to the occurrence of the effect, while the occurrence of a depth effect
      is not.

PMID- 11505614
TI  - Independent first- and second-order motion energy analyses of optic flow.
AB  - The human visual system contains a functional sub-system that is specialized to
      extract image motion. The sensitivities of neurons change as one moves higher in
      the pathway. Initially cells collect responses from small retinal areas but later
      those local signals are combined to extract global motion; either frontoparallel
      or radial motion relative to the center of the visual field. This sequence of
      processing is conducted in parallel by pathways sensitive to the motion of either
      the first- or second-order luminance statistics of the image. Previously it had
      been shown that these two pathways were independent at the level at which local
      motion signals and frontoparallel global motion signals are extracted. In this
      study independence is tested during the extraction of radial global motion; a
      process strongly associated with cortical area MST (or V6) and the next logical
      level in the motion pathway. We find that the two pathways do provide independent
      estimates of radial motion and are, therefore, independent at all levels of the
      motion pathway that have been tested to date.

PMID- 11505615
TI  - Hemispheric specialization in quantification processes.
AB  - Three experiments were carried out to study hemispheric specialization for
      subitizing (the rapid enumeration of small patterns) and counting (the serial
      quantification process based on some formal principles). The experiments consist
      of numerosity identification of dot patterns presented in one visual field, with
      a tachistoscopic technique, or eye movements monitored through glasses, and
      comparison between centrally presented dot patterns and lateralized
      tachistoscopically presented digits. Our experiments show left visual field
      advantage in the identification and comparison tasks in the subitizing range,
      whereas right visual field advantage has been found in the comparison task for
      the counting range.

PMID- 11505616
TI  - Imagined body orientation and perception of the visual vertical.
AB  - The existence of body orientation mental imagery was tested by examining whether
      self roll tilt imagery affects the subjective visual vertical (SVV). Twenty
      healthy subjects judged the orientation of a dim luminous bar with respect to
      gravitational vertical, while normally seated in complete darkness with their
      head firmly restrained earth vertically. SVV was measured in three conditions: a
      reference condition with no imagery, and a left and a right imagery condition,
      during which the bar orientation was to be judged while the subjects imagine
      themselves roll-tilted towards left or right, respectively. The imagined roll
      tilts were of the same magnitude as roll tilts which generally induce an E
      effect, i.e., an SVV lean toward the side opposite to those of body tilt. If
      imagery and perception of self roll tilt share common processes, self roll tilt
      imagery should induce an E-like effect. Results show an imagery-induced E-like
      effect, which strongly supports the idea that humans can perform mental imagery
      of body orientation about gravity.

PMID- 11505617
TI  - [Bilateral breast carcinoma and local recurrence: prevalence of BRCA-1 and BRCA-2
      gene mutations in an unselected patient sample].
AB  - BACKGROUND: Mutations of the BRCA 1/BRCA 2 genes strongly predispose towards the
      development of contralateral breast cancer. We therefore investigated a hospital
      based series of patients with bilateral breast cancer and a comparison group of
      patients with unilateral breast cancer, pairwise matched by age and family
      history, for mutations of the BRCA 1/BRCA 2 genes. PATIENTS AND METHODS: Between
      1995 and 2000 genomic DNA from blood samples of 75 patients with bilateral breast
      cancer, who received postoperative radiotherapy, was analyzed for mutations of
      all coding regions and flanking intron sequences of the BRCA 1/BRCA 2 genes by
      single strand conformation polymorphism analysis (SSCP) and sequencing of
      aberrant findings. The results were compared to 75 unilateral breast cancer
      patients who were screened for common mutations in the BRCA 1 and BRCA 2 genes.
      Treatment results of patients with bilateral disease were analyzed with regard to
      a possible carriership of a BRCA 1/BRCA 2 gene mutation. RESULTS: Five distinct
      frameshift deletions (one in BRCA 1, four in BRCA 2) were identified in six
      patients with bilateral breast cancer. Three of six carriers developed local
      relapse, whereas this was the case in only nine of 69 non-carriers. After
      radiotherapy local relapse occurred in five patients (five of 126 irradiated
      breasts or chest walls). Three of these patients (60%) were carriers of a
      pathogenic BRCA 1/BRCA 2 mutation. In the comparison group of patients with
      unilateral breast cancer three pathogenic BRCA 1 mutations were identified.
      CONCLUSIONS: We failed to confirm an increased prevalence of BRCA 1/BRCA 2
      mutations in our hospital-based series of patients with bilateral breast cancer.
      However, local relapse, especially when occurring after radiotherapy, may be
      predictive for an underlying pathogenic BRCA 1 and BRCA 2 gene mutation in
      patients with bilateral breast cancer.

PMID- 11505618
TI  - [Intraoperative radiotherapy (IORT) in treatment of breast carcinoma--a new
      therapeutic alternative within the scope of breast-saving therapy? Current status
      and future prospects. Report of experiences from the European Institute of
      Oncology (EIO), Mailand].
AB  - BACKGROUND: External beam radiation therapy (EBRT) represents an integral
      component of breast-conserving treatment. In published series it has been
      demonstrated that the external boost can be replaced by intraoperative
      radiotherapy (IORT) where irradiation at a single dose from 10 up to 15 Gy was
      safely delivered directly to the tumor bed. PATIENTS AND METHODS: At the European
      Institute of Oncology, Milan, we initiated a dose escalation study to investigate
      the feasibility of applying single doses of IORT from 10 Gy up to 22 Gy. A
      portable IORT equipment with different electron energies was used. From July to
      December 1999, a total of 65 patients with T1-2 (max. 2.5 cm) No-1 breast cancer,
      median age 58 years (range 33-80 years) was treated. Ten patients received 10 Gy,
      eight patients were treated with an IORT of 15 Gy, eight received 17 Gy, six had
      19 Gy, and 33 were treated with 21-22 Gy. Patients with 10 and 15 Gy received an
      additional EBRT of 44 and 40 Gy, respectively. In all other patients IORT was the
      sole radiation treatment. RESULTS: No acute side effects or intermediate untoward
      effects after a follow-up from three to nine months related to IORT were
      observed. CONCLUSIONS: Since the applicator can be safely placed under the
      control of the surgeon and radiotherapist IORT has the potential of accurately
      treating the tumor bed. Skin and subcutaneous tissue are not irradiated thus
      decreasing the potential risk of fibrosis and eventually obtaining a better
      cosmesis. With IORT single doses of 22 Gy being equivalent to a 60 Gy EBRT can
      safely be delivered. Even so the average time of operation was prolonged by
      around 20 minutes IORT application ultimately improves the quality of life of the
      patients in shortening overall treatment. Long-term follow-up is necessary to
      demonstrate whether large single doses of IORT might have the potential of
      sufficient local tumor control without major side effects. As a future
      perspective a randomized trial comparing EBRT with IORT as sole treatment will be
      performed.

PMID- 11505619
TI  - Interstitial brachytherapy with Ir-192 low-dose-rate in the treatment of primary
      and recurrent cancer of the oral cavity and oropharynx. Review of 318 patients
      treated between 1985 and 1997.
AB  - AIM: To evaluate the impact of postoperative interstitial brachytherapy with and
      without external radiotherapy in the treatment of primary and recurrent squamous
      cell carcinoma of the oral cavity and oropharynx. PATIENTS AND METHODS: Between
      1985 and 1997, a total of 318 patients were treated by interstitial Ir-192 low
      dose-rate brachytherapy as part of their primary (n = 236) or recurrent treatment
      (n = 82). There were 263 male (83%) and 55 (17%) female patients. The
      distribution of UICC (1997) stages was as follows: I (61 patients, 19%), II (71
      patients, 22%), III (58 patients, 18%), IV (128 patients, 40%). The primary tumor
      site was located in the oral cavity in 201 patients (63%), in the oropharynx in
      86 patients (27%), lower lip in 19 patients (6%) and other regions in twelve
      cases (4%). Treatment concepts did not vary over the time and were dictated by
      the initial tumor extension: a total of 175 patients (55%) received a combination
      of surgery, interstitial brachytherapy (23-25 Gy) and external radiotherapy (50
      60 Gy), 60 patients (19%) surgery and interstitial brachytherapy (45-55 Gy)
      alone. Advanced disease not amenable to primary surgery was either treated by
      radiochemotherapy and interstitial brachytherapy in 39 patients (12%) or a
      combination of interstitial brachytherapy, external radiotherapy and interstitial
      hyperthermia in 44 patients (14%). RESULTS: Overall survival rates following
      primary and recurrent treatment were 50 +/- 4% and 29 +/- 5%, respectively, at 5
      years (p < 0.0001). A significant impact on overall survival rate was noted for
      UICC stage: patients in stage I/II had survival rates of 64 +/- 5% and 57 +/-
      10%, respectively, while patients in stage III/IV had survival rates of 39 +/- 5%
      and 15 +/- 5%, respectively, at 5 years (p < 0.0001). In addition, grading (p =
      0.01) and hemoglobin levels (p = 0.05) had a significant influence on overall
      survival. Local tumor control rates for all patients were 74 +/- 3% and 57 +/- 7%
      at 5 years following primary and recurrent treatment (p = 0.01), respectively.
      The 145 patients treated for primary disease by a uniform concept of surgery,
      interstitial brachytherapy and external radiotherapy achieved excellent local
      control rates with 92 +/- 4% (stage I/II) and 65 +/- 6% (stage III/IV) at 5
      years. Late treatment-related toxicity with soft tissue necrosis and/or
      osteonecrosis requiring mandibular resection was 7.5%. CONCLUSION: Local tumor
      excision followed by postoperative interstitial brachytherapy with and without
      external radiotherapy is associated with excellent locoregional control, a low
      risk of chronic sequelae and may therefore considered as a new approach avoiding
      mutilating radical surgery.

PMID- 11505620
TI  - [3 years experience with low dosage fractionated percutaneous teletherapy in
      subfoveal neovascularization. Clinical results].
AB  - AIM: The effect of low dose fractionated percutaneous teletherapy to visual
      acuity and the changes in subfoveolar neovascular membranes in age-related
      macular degeneration were investigated. PATIENTS AND METHOD: 126 eyes of 118
      patients (age 55-89 years; mean 74 ys.) were treated. Best distal and near visual
      acuity was assessed prior to (= initial visual acuity [IVA]) and 3, 6, 12, 18,
      24, 30 and 36 months after teletherapy. Fluorescein angiography was performed
      prior to and 6, 12, 24 and 36 months after radiation therapy. For analysis
      patients were divided into different groups by IVA and membrane size. Maximal
      duration of observation was 36 months. Teletherapy was done by a 9-MeV photon
      linear accelerator through a lateral port in half-beam technique with a single
      dose of 2 Gy up to a total dose of 20 Gy within 12 days. RESULTS: No severe
      negative side effects have been observed. Eight patients reported of epiphora and
      four patients complained of transient sicca syndrome. Visual acuity decreased
      more than one line in the group IVA 0.05-0.2. The group IVA 0.3-0.5 remained
      unchanged for 1 year. We found a tendency for increased visual acuity in group
      IVA > or = 0.6 for 18 months. After that time both groups showed decreased visual
      acuity, but all these patients reported of reduced metamorphopsia and increased
      color and contrast perception. CONCLUSIONS: There is an influence of low dose
      fractionated percutaneous teletherapy on visual acuity, subfoveal neovascular
      membranes and metamorphopsia. IVA and duration of anamnesis play an important
      role. There seems to be no persistent effect; possibly increased dosage will
      bring a benefit.

PMID- 11505621
TI  - [Late radiation changes after small volume radiosurgery of the rat brain.
      Measuring local cerebral blood flow and histopathological studies].
AB  - BACKGROUND: The goal of this study was to investigate late effects following
      stereotactic single fraction and small volume irradiation on cerebral blood flow
      and histologic alterations in the rat brain parenchyma. MATERIAL AND METHODS: 66
      Copenhagen rats, separated into eleven groups of six animals each received single
      doses of 20, 30, 40, 50 and 100 Gy using a 15 MV linear accelerator. Six rats
      served as controls. Two cylindrical collimators of 2 mm and 3 mm aperture were
      used. The diameters of the spherical 80% isodose were 3.7 and 4.7 mm,
      respectively (Table 1). Irradiation was applied to a predefined area in the right
      frontal lobe. 19 months after irradiation local cerebral blood flow (LCBF) was
      measured by the autoradiographic method in one animal of each dose group between
      20 and 50 Gy. 9 and 19 months after irradiation, half of the animals of each
      group were sacrificed for brain histology. All animals irradiated with 100 Gy
      were sacrificed 7 months after irradiation. RESULTS: An increase of local
      cerebral blood flow was measured in brain structures within the 80% isodose in
      animals irradiated with 50 Gy (Figure 3) compared to the contralateral
      hemisphere. Measurements close to necrotic areas showed a strong decrease of
      local cerebral blood flow (Figure 1). A volume increase of the irradiated
      hemisphere was seen after 19 months (Figure 2). The histologic examination after
      19 months showed necrotic areas in the 30-50 Gy groups (Figure 4b) but not in the
      20 Gy groups (Figure 4c). The animals who received 100 Gy demonstrated brain
      necrosis within 9 months after irradiation (Figure 4a). At both points in time
      the groups irradiated with the 3-mm collimator showed more pronounced
      histomorphologic and functional changes compared to the groups irradiated with
      the 2-mm collimator. CONCLUSION: Alterations of the local cerebral blood flow
      were measured as a late effect after single dose irradiation. The alterations of
      the local cerebral blood flow could be explained by the histomorphologic changes
      of the blood vessels. Using a semi-quantitative classification a dose, time and
      volume dependence for the endpoint radionecrosis was seen.

PMID- 11505622
TI  - Impact of treatment acceleration and its timing on the response of the
      rhabdomyosarcoma R1H of the rat to fractionated irradiation.
AB  - BACKGROUND AND PURPOSE: In clinical practice a concomitant boost is usually given
      as a second daily dose to a reduced field. The question arises which part of
      treatment should be accelerated to achieve optimal tumor control. An experiment
      was performed on tumor bearing rats to determine the optimal timing of treatment
      acceleration for this experimental tumor system. MATERIAL AND METHODS:
      Rhabdomyosarcoma R1H of the rat were treated applying 30 fractions in an overall
      treatment time of 40-42 days, up to total doses ranging from 67.5 to 97.5 Gy were
      administered. For control a standard treatment was given as continuous treatment
      applying one fraction per day. A boost of five additional fractions was given as
      a second fraction during 5 days. Three experimental arms received a boost either
      in the 1st, 4th, or in the last week of treatment. Treatment outcome was assessed
      using tumor control as endpoint. RESULTS: All experimental arms proved more
      effective than the standard treatment. Treatment was most effective when the
      boost was administered in the 1st week of treatment. A TCD37% of 87.1 Gy (95% CI:
      82.8 ... 92.7 Gy), 96.5 Gy (89.9 ... 107.1), and 107.3 Gy (97.2 ... 131.0) was
      determined, when the boost was given in the 1st, 4th, or last week of treatment,
      respectively. The observed difference between the experimental arms was
      statistically significant (p = 0.004). CONCLUSIONS: Initially accelerated
      treatment schedules were found to be more effective for tumor control in an
      experimental tumor system.

PMID- 11505623
TI  - [Risk and prognosis of corpus carcinomas after tamoxifen treatment of breast
      carcinoma].
AB  - BACKGROUND: Dysphagia after radiotherapy of thoracic tumors may be caused by
      recurrences or by radiation damage to the esophagus. CASE REPORT: A 75-year-old
      patient presented with a complete obstruction of the esophagus 5 months after
      CHARTWEL radiotherapy for a non-small cell lung cancer. During the last week of
      radiotherapy mild dysphagia (Grade 1 EORTC/RTOG, Grade 2 MRC-CHART-Score)
      occurred that persisted over the following months. X-ray and endoscopic
      investigations revealed an easily removable food bolus without evidence of
      esophageal stricture or ulceration. CONCLUSION: The case report describes a mild
      but prolonged early radiation reaction of the esophagus. In comparison with
      conventional fractionation the incidence of dysphagia is higher after accelerated
      fractionation schedules. The pathophysiologic mechanisms underlying persistent
      dysphagia are currently unknown. Beside of recurrences, radiation effects to the
      esophagus should be considered if dysphagia after irradiation of thoracic tumors
      occurs, because, as in this case, therapy may rapidly improve the symptoms.

PMID- 11505624
TI  - [Problematic results of a randomized study of neoadjuvant radiochemotherapy of
      operable esophageal carcinoma].

PMID- 11505626
TI  - [Molecular genetic changes in hypophyseal adenomas].

PMID- 11505627
TI  - [Remembering DEGRO 2000-evaluation of the refresher course survey].
AB  - BACKGROUND: Refresher courses as presented at the annual DEGRO meeting are
      important parts in the continuous training of radiotherapists. For further
      quality improvement, knowledge about the participants' needs is essential.
      METHODS: During the DEGRO meeting 10/2000 in Munich, participants of refresher
      courses were encouraged to grade the presentations with regard to six questions
      with marks from 1 ("very good") to 6 ("not acceptable"). Free comments were
      welcomed. The individual results were handed over to future organizing committees
      and the speakers themselves, cumulative results can be read up in the present
      note. RESULTS: Approximately 1,000 participants of refresher courses filled in
      381 questionnaires concerning 24 different training sessions. Altogether 48.5% of
      all answers said "very good", 31.7% "good" and 11.1% "satisfactory" (all worse
      marks together 3%, no statement in 5.7%). Free comments dealt mainly with
      handouts and a later starting time for the refresher courses than 7:30 a.m.
      CONCLUSION: Participants of the annual DEGRO meeting show a great amount of
      interest in refresher courses and seem to be quite content with the present
      findings. First steps are taken to get the proposals under way.

PMID- 11505628
TI  - Clinical laboratory in the third millennium.

PMID- 11505629
TI  - Clinical varieties of mastocytoses.
AB  - Varieties of the clinical features of mastocytoses, also called mastocytosis
      syndrome, are presented. The disease is characterized by excessive accumulation
      of mast cells, their proliferation and action in the skin and other organs, even
      in the central nervous system. The mastocytosis syndrome was known as early as
      the second half of the 19th century under the term urticaria pigmentosa, and was
      histologically confirmed by the presence in the dermis of metachromatic cells,
      i.e. Ehrlich mast cells with red-purple cytoplasmic granules visible with Giemsa
      or toluidine blue stains. The mastocytosis syndrome was then supposed to be a
      benign chronic dermatosis of childhood with spontaneous regression by
      adolescence. The clinically pathognomonic symptoms of Darier's sign (urtication
      of primary skin lesion upon rubbing) and flushing help in the diagnosis of
      mastocytosis syndrome. In the 1950s, there was a progression in the diagnosis of
      systemic mastocytosis achieved by scientists and clinicians of various
      specialties. Upon the discovery of many mast cell released mediators (heparin,
      histamine, leukotrienes, prostaglandins, proteases, cytokines), receptor
      functions, relationship to IgE, anaphylatoxin, etc., they were recognized as
      triggers of various clinical features of the mastocytosis syndrome. In this
      paper, different forms of cutaneous and systemic mastocytosis are described, with
      special reference to 'mastocytosis mucocutanea haemorrhagica' observed by one of
      the authors in a female infant and followed from 6 months till 2.5 years of age.
      The patient showed practically all the diverse forms of cutaneous mastocytosis:
      urticaria pigmentosa, papular, nodular, tumorous-like melanoma, vesiculobullous,
      erythrodermic, telangiectasia eruptiva maculosa perstans. She also suffered from
      nasal and rectal hemorrhage, conjunctival suggillations, plaque-like
      infiltrations of the glossal, oropharyngeal and laryngotracheal mucosa, episodes
      of flushing, and transitory apnea. It is emphasized that the diagnosis of
      mastocytosis syndrome may be difficult for its mimicking various other diseases.
      The occurence of mastocytosis syndrome from the neonatal period through adult and
      old age, and possibilities of symptomatic treatment and prevention of sudden
      death or fatalities are discussed. Familial occurrence of mastocytosis syndrome
      and new genetic studies that may prove highly useful for understanding the
      etiopathogenesis of mastocytosis syndrome are described.

PMID- 11505630
TI  - Experimental and clinical study in the treatment of sigmoid volvulus.
AB  - The aim of the study was to introduce an alternative surgical procedure for the
      treatment of primary volvuius of the sigmoid colon. Sigmoid colon plication was
      performed in 42 dogs, and afterwards in six patients. The procedure consists of
      systematic plaiting the sigmoid colon wall with interrupted serosubmucosal 3/0
      Vicryl sutures along the whole circumference, except on the mesenteric border.
      Five parallel circular folds were done in dogs, and 20-30 folds in patients, with
      appropriate bowel length reduction. In the experimental study, dogs were randomly
      divided into three experimental and one control group of 14 animals each. The
      group 1 dogs were sacrificed on day 8, group 2 dogs on day 15, and group 3 and
      control group dogs on day 30 postoperatively. On exploration, sigmold colon
      adhesions were found in 6 (14.3%) animals. Intestinal wall and lumen were normal.
      In the clinical study, six patients with sigmoid volvulus were operated on within
      6-8 hours of admission. A viable colon was a prerequisite for the sigmoid
      plication procedure. The operating time was 60-90 minutes. Recovery was
      uneventful, with average hospitalization 11 (range 8-15) days. No volvulus
      recurrence was recorded during the three-year follow-up. Based on our
      experimental and clinical data, we believe that the plication procedure could be
      appropriate treatment in some selected patients with volvulus of the sigmold
      colon.

PMID- 11505631
TI  - Angiotensin-converting enzyme gene polymorphism in patients with systemic lupus.
AB  - The renin-angiotensin-aldosterone system (RAAS) has been considered one of the
      probable pathophysiologic mechanisms involved in disease progression. Genetic
      polymorphism of the RAAS has been associated with the clinical course of renal
      disease. One of the genetic polymorphisms is a deletion or insertion of a 287
      base pair fragment in intron 16 of the angiotensin-converting enzyme (ACE) gene.
      It is known that ACE gene polymorphism is present in humans and that it is
      associated with an increased risk of cardiovascular diseases, renal disease
      progression and sarcoidosis. In this study, the potential significance of ACE
      gene polymorphism in patients with systemic lupus erythematosus (SLE) was
      investigated. ACE gene polymorphism was determined in 18 patients with SLE and in
      21 healthy volunteers as a control group. The mean age of patients was 38.5
      years. All patients had a mean follow-up of 30.7 +/- 20.2 months (range 5-95
      months). ACE genotypes were determined by the method of polymerase chain
      reaction. Proteinuria and creatinine were also followed. The frequency of DD, ID
      and II genotypes was 50%, 28% and 22% in SLE patients and 25%, 50% and 25% in
      healthy controls, respectively. DD genotype was more common in SLE patients than
      in the control group. The patients with II genotype had lower proteinuria and
      creatinine level than those with DD genotype (p < 0.05). The time to disease
      remission was shorter in patients with II genotype (p < 0.05). Study results
      indicated an increased frequency of D allele in SLE patients. The increased ACE
      activity in these patients pointed to the need of further studies of ACE gene
      polymorphism in SLE.

PMID- 11505632
TI  - Changes of intratympanic pressure in secretory otitis media.
AB  - A thick, gluey effusion was observed to out of the middle ear after myringotomy
      only in some cases of secretory otitis media. Cytologic analysis of intratympanic
      transudate in 321 cases of secretory otitis media in children showed the cellular
      infiltration to result in increased viscosity of the middle ear content. It
      caused gradual change in the middle ear pressure, from the initially negative to
      positive pressure in the advanced stages of the disease.

PMID- 11505633
TI  - Acute pancreatitis in the Zabok General Hospital.
AB  - Acute pancreatitis is an acute disease of the pancreas due to the organ
      autodigestion. The disease is still burdened with numerous complications and
      quite frequently with lethal outcome, in spite of the sophisticated diagnostic
      and therapeutic methods currently available. The disease has a benign course in a
      majority of patients (80%), however, in the remaining 20% it assumes a malignant
      course with the development of massive necroses of the pancreatic and
      peripancreatic tissues, infection, hemorrhage, and endogenous intoxication with
      lesions of the lungs, kidneys, heart and liver. The biliary tract disease plays
      the major role in the etiology of acute pancreatitis (80%), followed by
      alcoholism (10% to 15%). This differs from the experience acquired at the Zabok
      General Hospital, where an almost identical incidence of biliary and ethylic
      etiology was recorded. Other, less common causes include post-traumatic,
      postoperative, infective and hormonal (hyperparathyroidism) etiology. In some
      cases, the cause of acute pancreatitis remains unknown. The disease shows a
      female predominance, which results from the higher prevalence of cholelithiasis
      in women than in men. Anatomically, there are two main forms of acute
      pancreatitis, interstitial or edematous form, and hemorrhagic necrotizing form.
      The interstitial or edematous form of acute pancreatitis is characterized by
      edema (exudation) of the pancreatic interstitium. The hemorrhagic necrotizing
      form of acute pancreatitis is characterized by autodigestion of a minor or major
      portion of the pancreas and peripancreatic tissues. The diagnosis of acute
      pancreatitis may initially pose a considerable problem. Decision on the mode of
      treatment should primarily be based on the clinical picture and supported by
      relevant laboratory parameters and other diagnostic procedures (ultrasonography,
      computed tomography). Conservative therapy is indicated for the edematous form of
      acute pancreatitis, whereas operative treatment is as a rule used for the
      necrotizing form of acute pancreatitis. Secondary bacterial contamination of the
      necrotic foci with the development of septic complications occurs in more than
      50% of patients with the necrotizing form of acute pancreatitis, and is an
      absolute indication for surgical intervention. The modes of treatment used in 57
      patients admitted for acute pancreatitis during the 1996-1999 period are
      described. Cholelithiasis was the cause of acute pancreatitis in 28 (49.1%), and
      alcoholism in 29 (50.9%) patients. Conservative treatment was used in 41 (72%)
      patients. Sixteen (28%) patients underwent operative treatment. Explorative
      laparotomy and drainage were performed in four patients, and explorative
      laparotomy, necrectomy, sequestrectomy and drainage with two or more drains in 11
      patients. Cholecystectomy and T drainage along with necrectomy and drainage were
      performed in one patient. There were 12 (21%) patients with the most severe form
      of acute pancreatitis. Nine of these patients were operated on (necrectomy
      drainage) between day 6 and 10 of the disease. Two of these patients had to be
      reoperated on within a month, due to necrosis and abscess recurrence. Three of
      the 12 patients with the severe form of acute pancreatitis received conservative
      therapy. Fifteen patients were operated on 8-10 weeks after acute pancreatitis
      had subsided. Pseudocysts developed in three patients. These patients were
      operated on 6-8 weeks from the onset of disease, with internal drainage via
      isolated small intestine flexure performed in all of these patients. The mean
      duration of intensive care unit stay for all patients with acute pancreatitis was
      20.6 days. Four of 57 patients hospitalized for acute pancreatitis died. The
      mortality rate in the group of patients with the severe form of acute
      pancreatitis (n = 12) was 33%. Complications developed in 50% of operatively
      treated patients.

PMID- 11505634
TI  - The prevalence of anaerobic infection in pilonidal sinus of the sacrococcygeal
      region and its effect on the complications.
AB  - Bacteriologic characteristics of pilonidal disease of the sacrococcygeal region
      were assessed in two groups of patients: patients with disease recurrence (group
      A), and patients who first ever presented for surgical treatment (group B). The
      frequency of anaerobic colonization was studied. Bacterial colonization is
      frequently present in patients with pilonidal disease of the sacrococcygeal
      region. Samples of the skin over the sacrococcygeal sinus showed the presence of
      bacterial colonization in 78% and 70% of group A and group B patients,
      respectively. Analysis of sinus fluid samples revealed the presence of bacteria
      in 88% of group A patients and 78% of group B patients. Anaerobic colonization in
      the content of pilonidal sinus was found in approximately 2/3 (64%) group A
      patients and about a half (52%) group B patients. Considerable bacterial
      colonization was also recorded in skin swab samples, i.e. in 48% of group A
      patients and 38% of group B patients. Anaerobic bacteria were rarely detected in
      pure cultures (in group A 6% skin swab, and 20% of sinus fluid samples, and in
      group B, 4% of skin swab and 12% of sinus fluid samples). Anaerobes were mostly
      detected in combined cultures (42% of skin swab and 44% of sinus fluid samples
      from group A, 32% of skin swab and 40% of sinus fluid samples from group B).
      Surgical methods to considerably reduce the conditions for anaerobic bacterial
      colonization of the wound should be the methods of choice in the management of
      pilonidal disease of the sacrococcygeal region.

PMID- 11505635
TI  - Flail chest stabilization with palacos prosthesis.
AB  - The approach and management of patients with post-traumatic flail chest continue
      to be a controversial issue. A method of surgical stabilization of flail chest
      using palacos, a cement-like material is described. A ready-made prosthesis is
      placed on the external side of the ribs vertically bridging the flailed chest
      segment, and fixed to the first upper and first lower intact rib as well as to
      the mobile segments of the affected ribs. Surgical fixation was carried out in 56
      patients. The results proved the method to be a simple and effective procedure.

PMID- 11505636
TI  - Pelvic neurilemmoma.
AB  - A case of a 37-year-old man admitted to our Department of Internal Medicine for
      medical evaluation of hypertension is reported. The patient had a 4-year history
      of oscillating hypertension prior to admission, however, with no major subjective
      complaints, except for pollakisuria. Clinical and biochemical assessment revealed
      no damage to target organs. Laboratory parameters showed normal values, except
      for hyperlipidemia. On routine ultrasonography of the pelvis confirmed a pelvic
      tumor of uncertain etiology, with no abdominal lymph node enlargement. No signs
      of metastasis were found. The patient was transferred to the Department of
      Surgery, where the tumor was removed in toto. Histopathologic analysis of the
      tumor, 11 x 8 x 8 cm in size, composed of cellular and mixoid areas with traces
      of collagenous connective tissue, necrosis, and tiny calcifications with
      scattered palisading nuclei and Verocay bodies, pointed to the diagnosis of a
      benign tumor, i.e. neurilemmoma. Postoperatively, the patient's subjective state
      was excellent, with normal blood pressure values, and without pollakisuria. A
      very large space-occupying lesion was responsible for compression of the
      neighboring organs, especially urinary bladder, resulting in pollakisuria. To our
      knowledge, pelvic localization of neurilemmoma, particularly a large one, is
      rare.

PMID- 11505637
TI  - [Organization of the Helicobacter pylori genome].
AB  - Helicobacter pylori is a Gram-negative, spiral-shaped pathogenic bacterium that
      was firstly isolated and cultured from biopsy specimens by Marshall and Warren in
      1983. This organism is a human gastric pathogen associated with peptic ulcer
      disease as well as chronic gastritis. Recent epidemiological studies have
      demonstrated that H. pylori is a primary risk factor for the development of
      intestinal type gastric adenocarcinoma. H. pylori is the first bacterium for
      which the genomes of two unrelated strains (26695 and J99) have been sequenced.
      The genome of H. pylori is relatively low in size (1.6-1.73 Mb). In this review,
      we compare the organization of two sequenced H. pylori genomes. A special
      emphasis on genetic diversity of H. pylori including plasticity zone and cag
      pathogenicity island has been placed.

PMID- 11505638
TI  - [Inhibitors of neoangiogenesis in antineoplastic therapy].
AB  - The role of angiogenesis in tumor growth and metastasis is discussed. The
      endogenous activators and inhibitors of tumor angiogenesis are presented and
      their mechanisms of action are reviewed. An overview on angiogenesis as a new
      potential target of antitumor therapy is described. The clinical trials of
      various antiangiogenic agents are briefly summarized and their differential
      mechanisms of action are discussed.

PMID- 11505639
TI  - [About side effects of platinum drugs].
AB  - The work presents current view about toxic effects of platinum anticancer drugs.
      In the first part, the toxic effects of cisplatin as nephrotoxicity, ototoxicity,
      myelosuppression, anaphylactic-like reactions, neurotoxicity and gastrotoxicity
      are presented. The second part describes mechanisms of nephrotoxicity of
      cisplatin. In the third part, the toxicity of carboplatin and iproplatin are
      reviewed.

PMID- 11505640
TI  - [Cholecystokinin--hormone and neuromodulator].
AB  - Cholecystokinin (CCK) is a polipeptide having many functions in digestive system
      (regulating motor activity and secretion) and acting as a neuromodulator in
      central and peripheral nervous systems. Recent research shows that CCK increases
      insulin and glukagon secretion and activates hypothalamo-pituitary-adrenal axis.
      It also plays a role in cardiovascular system (CCK has a positive inotropic
      effect). The aim of this study is to show some recent knowledge in the subject of
      CCK structure and its function in human body.

PMID- 11505641
TI  - [GP IIb/IIIa receptor antagonists--molecular and clinical aspects].
AB  - Recently many investigators have found that platelet glycoprotein GP IIb/IIIa is
      responsible for platelet aggregation and plays a pivotal role in acute coronary
      thrombosis. Thus, GP IIb/IIIa antagonists may play an important role by
      inhibiting platelet aggregation and their binding to fibrinogen. Drugs that
      antagonize this binding have been developed for the treatment of thrombotic
      diseases and acute coronary syndrome. Now, there are three groups of platelet
      receptor antagonists: monoclonal antibodies, synthetic peptides and non-peptide
      antagonists. As a result of large clinical trials the potency of those compounds
      in preventing of coronary thrombosis have been demonstrated. In this article
      molecular aspects of GP antagonists action and selected clinical trials have been
      presented.

PMID- 11505642
TI  - [Ischemia-reperfusion injury of the liver].
AB  - There is no single factor responsible for liver injury after its temporary
      ischemia and reperfusion. We deal with a mosaic of biochemical processes, in
      which a number of cells, mediators and enzymatic systems take part. The mechanism
      of liver injury remains far from full explanation.

PMID- 11505643
TI  - [Hematopoietic cytokines as tumor markers].
AB  - Serum tumour markers may be helpful in early diagnosis of cancer, in the initial
      assessment of the extent of the disease, and in monitoring of the tumour growth
      or tumour volume reduction, once cancer has been diagnosed and treatment started.
      Recent studies have focused on a new family of markers--hematopoietic cytokines.

PMID- 11505644
TI  - [Changes in intracellular protein degradation during the aging of an organism].
AB  - This review describe the influence of free radicals on the protein degradation
      during aging. The consequences of aging are changes in susceptibility of proteins
      on the proteases action as well as changes in cell proteolytic systems activity
      in different organs.

PMID- 11505645
TI  - Recurrent Spigelian hernia: a rare cause of colonic obstruction.
AB  - Spigelian hernia is considered a surgical rarity. Recent articles describe only
      six recurrent hernias and a scant number of patients with colonic obstruction
      resulting from incarceration. A patient with intestinal obstruction resulting
      from recurrent Spigelian hernia with strangulated colon is described. The patient
      underwent tension-free repair using a prosthetic mesh. Recent literature suggests
      that the deficiency of connective tissue in patients with hernias justifies the
      widespread use of permanent mesh for tissue reinforcement and avoidance of
      recurrences. The rare case presented should be regarded as an illustrative
      example for application of the tension-free repair principle in the definitive
      management of recurrent Spigelian hernia.

PMID- 11505646
TI  - Use of polypropylene prostheses for strangulated inguinal and incisional hernias.
AB  - We used monofilament polypropylene prostheses in 20 emergency operations for
      strangulated hernias. Sixteen of the operated patients had groin hernias (five of
      them recurrent), two had incisional and one had a Spigel's type hernia.
      Intestinal resection was performed because of bowel wall necrosis in one of the
      patients. During the postoperative period, we observed only one minor
      complication (a seroma formation). During the follow-up, no recurrence was
      observed. In our opinion, the use of monofilament polypropylene mesh in emergency
      hernia operations is safe, simple and effective.

PMID- 11505647
TI  - Colocutaneous fistula due to polypropylene mesh.
AB  - Fistulae due to polypropylene mesh are known to occur if the prosthetic mesh is
      placed close to a hollow viscus. Some cases of enterocutaneous fistula have been
      reported but there are few cases of fistula affecting the large bowel. It is
      important to recognize these cases because they are severe complications of the
      prosthesis and difficult to manage. We present a case of colocutaneous fistula
      caused by fragmentation of polypropylene mesh and erosion into the sigmoid colon
      after recurrent incisional hernia repair.

PMID- 11505648
TI  - Erosion and perforation of colon by synthetic mesh in a recurrent paracolostomy
      hernia.
AB  - Parastomal hernia, particularly when recurrent, presents a troublesome problem to
      the surgeon. Since the late 1970s, prosthetic-mesh repairs have been used
      increasingly, though, as yet, there is no consensus on the best technique of
      repair. We report a case of failure of a polypropylene-mesh repair of a recurrent
      parastomal hernia, complicated by erosion of the mesh edge into the colon
      proximal to the stoma. This entailed further resection of the colon, excision of
      the mesh and relocation of the colostomy. The case highlights the potential for
      serious morbidity from this form of repair and the need for careful assessment of
      symptoms before contemplating a surgical approach to any type of parastomal
      hernia.

PMID- 11505649
TI  - The influence of differing pore sizes on the biocompatibility of two
      polypropylene meshes in the repair of abdominal defects. Experimental study in
      dogs.
AB  - Two types of monofilament polypropylene meshes of markedly different
      construction, configuration and pore size were compared and used to repair full
      thickness muscle defects in the abdominal wall of 22 mongrel dogs to assess their
      biocompatibility with host tissues. The defects were repaired with Prolene
      (Ethicon) woven mesh (pore size = 164 x 96 microns) and with an experimental,
      extruded mesh called T mesh (pore size = 3 mm x 4 mm). On the 30th postoperative
      day, the animals were sacrificed, and the segments of the abdominal wall
      containing the implanted meshes were excised. Although the Prolene mesh had
      greater tensile strength before implantation, 30 days after implantation, the T
      mesh showed similar tensile strength to Prolene mesh. The collagen densitometry
      showed a significant increase of total and mature collagen type I deposition in
      the T mesh. This suggests that the increased mature collagen type I deposition
      significantly increases the tensile strength of the reinforced mesh tissue and
      that the larger pore in the T mesh contributed to this finding by allowing
      increasing fibber orientation within the pores as a result of in vivo tension.

PMID- 11505650
TI  - Hernia clinic in a teaching institution: creation and development.
AB  - The hypothesis that a hernia clinic could improve the results of external
      abdominal wall herniorrhaphy was tested in a teaching institution. From 1980 to
      1988, all patients exhibiting external abdominal wall hernias were treated under
      protocol and separate from general surgical patients in a hernia clinic directed
      by a dedicated surgeon. The incidence of recurrence, infection, and testicular
      ischemia was significantly better than our previous institutional results. The
      incidence of incarceration/strangulation also fell significantly in patients over
      65 years of age. Chart documentation was kept up to date for the duration of the
      project. Insufficient emphasis by the Clinic Director on the benefits of the
      proposed protocol and other factors contributing to the eventual clinic closure
      could be circumvented by better alternative planning. In our institution, the
      outcome of surgery for external abdominal wall surgery was significantly improved
      by the creation of a hernia clinic; our results equal those reported by other
      recognized herniorrhaphists. Barring some developmental obstacles, the concept of
      a hernia clinic should be advantageous to patients and residents alike.

PMID- 11505651
TI  - Modifications to Rives technique for midline incisional hernia repair.
AB  - Between 1990 and 1997, 284 patients were treated in our hospital for abdominal
      hernias. In the original group, 239 patients (84.15%) had midline hernia, and 45
      (15.8%) had lateral hernia. A total of 152 midline hernia patients (63.5%) were
      treated using our variant of Rives technique. In all these cases, preperitoneal
      and retromuscular polypropylene mesh was used as a reinforcement and was
      subsequently attached by means of absorbable sutures to the external border of
      the rectus muscles. There were no deaths. A total of 42 of all patients operated
      on (27.6%) suffered from long-term postoperative pain. In seven cases (4.6%) it
      was necessary to remove the prosthesis because of chronic infection, and there
      were two recurrences in patients in whom the prosthesis had to be removed. In our
      experience, the Rives technique is a suitable and safe treatment for the repair
      of midline incisional hernias. The use of absorbable sutures and fixation of the
      mesh to the external oblique aponeurosis can reduce the original problems of
      abdominal pain and unaesthetic skin scars.

PMID- 11505652
TI  - Minimally invasive operation techniques for inguinal hernia: spectrum of
      indications in Austria.
AB  - At the beginning of the 1990s, the introduction of endoscopic surgery led to the
      surgical treatment of hernias being reconsidered. At present, there are three
      groups of surgical procedures: conventional procedures (Shouldice, Bassini),
      open, tension-free mesh procedures (Lichtenstein, Gilbert, Rutkow) and endoscopic
      procedures, predominantly transabdominal preperitoneal hernioplasty (TAPP) and
      total extraperitoneal hernioplasty (TEP). The debate about the optimum treatment
      for hernias provoked by the endoscopic procedures is understandable in view of
      the large number of hernia operations performed. Numerous studies, some
      randomised, have demonstrated both advantages and disadvantages for the
      individual surgical procedures. In addition to the recurrence and complication
      rates, the cost factor and socio-economic aspects of the operations are playing
      an increasingly important role in deciding which method should be used. In
      December 1995, Austrian surgeons concerned with the problems of hernia repair
      both before and since the introduction of laparoscopic hernia repair came
      together for a consensus conference. During the meeting, the relevant aspects
      were summarised and a range of indications were established for surgical
      interventions. The main recommendation was that conventional open surgery, which
      can be performed under local anaesthesia, is indicated in unilateral
      uncomplicated primary hernias. Endoscopic hernioplasty is indicated if the
      contralateral findings are inconclusive or the hernia is bilateral or recurrent.
      The Zurser Hernienforum (Zurs Hernia Forum) has now been founded. The function of
      this forum is to carry out a prospective randomised study of inguinal hernia
      surgery throughout Austria.

PMID- 11505653
TI  - Experience--the key factor in successful laparoscopic total extraperitoneal and
      transabdominal preperitoneal hernia repair.
AB  - To emphasize the importance of the experience of the operating team, we compared
      the two largest materials in the total extraperitoneal (TEP) and the
      transabdominal preperitoneal (TAPP) procedures in Poland. We performed 1225
      procedures on 1110 patients (368 TEP and 809 TAPP). The experience of the
      operating teams measured by the mean number of procedures/surgeon was comparable.
      The mean operating time and hospitalization duration did not differ markedly.
      There was no procedure-related mortality. Intraoperative complications were
      infrequent. The ratio of early local complication (neuralgia, hematoma, and
      seroma) was slightly higher in the TEP group. We observed a higher recurrence
      rate following the TAPP procedure (2.84% vs 1.92%). However, after excluding the
      learning period this dropped markedly to much lower, comparable values (TEP:
      0.98%; TAPP: 1.14%). In laparoscopic hernia repair the experience of the
      operating team seems to be more important than choice of technique (TEP vs TAPP).

PMID- 11505654
TI  - Inguinal hernia: a patch covering only the myopectineal orifice is effective.
AB  - A large mesh in the preperitoneal space, spread on iliac vessels and bladder, can
      cause future difficulties in a case of urogenital or vascular disease. Since all
      recurrences are located in the area of the myopectineal orifice, a mesh covering
      only this area, as in the Rives procedure, is effective and avoids these
      drawbacks. However, the Rives procedure is demanding, which is why we tried to
      simplify the technique. A mesh 8-10 cm long and 6-7 cm wide was spread in the
      preperitoneal space using the inguinal approach, without any fixation or with
      only a few stitches; the fascia was then simply approximated over the mesh
      without tension. A total of 161 hernias (99% Nyhus type III and IV) were repaired
      using this technique. Only six benign complications (3.7%) occurred. With a
      median follow-up of 63 months (range, 18-94 months), only one recurrence occurred
      (0.7%), due to misplacement of the mesh, eight patients complained of mild pain,
      and no late complications were observed. In conclusion, placement of a small mesh
      covering only the myopectineal orifice using the inguinal approach is effective
      and is associated with a low risk of drawbacks and complications.

PMID- 11505655
TI  - Long-term recurrence after laparoscopic surgery of inguinal hernias.
AB  - Laparoscopic treatment of inguinal hernias has expanded rapidly during the last
      decade. Several studies have evaluated the early results of this technique, and
      the rate of recurrence was estimated less than 5% with a range from 0.5% to 10%.
      The long-term recurrence after such treatment is still not well known. This study
      reports the 2 year follow-up of laparoscopic treatment of 236 inguinal hernias
      (220 patients) from January 1996 to December 1997. All patients were contacted by
      telephone, 196 (90%) (193 men and 3 women) were examined by a senior surgeon. The
      average time from operation to examination was 34 months (range 20-42 months). We
      observed a 15% recurrence rate (35 hernias in 34 patients) of which 5% (12 cases)
      were symptomatic but 10% (23 cases) were totally asymptomatic and diagnosed on
      clinical examination. The postoperative inguinal haematoma and the physical
      activity of the patients seem to predispose the recurrence. Chronic pain was
      rarely observed in this study.

PMID- 11505656
TI  - Special aspects of neonatal inguinal hernia and herniotomy.
AB  - In a retrospective study, we examined 23 pre-term infants (18 boys, 5 girls) with
      a median weight of 1540 g (range 720-2770 g) and a median age of 32 weeks (range
      25-36 weeks) gestation, who were subsequently operated on after a median of 65
      days (range 20-121 days) for 33 inguinal hernias. The infants were evaluated with
      respect to concomitant diseases as well as peri- and postoperative complications.
      The following surgical procedure was used in all patients: a high suture ligation
      after excision of the hernia sac, followed by closure of the groin according to
      Grob in boys, and according to Bassini in girls. Co-morbidity was high in the pre
      term infants, both pre- and perinatally. Despite this high co-morbidity and a
      high rate of emergency operations due to incarcerations, the postoperative
      complication rate was very low. However, the rate of testicular atrophy (10%) and
      recurrent inguinal hernia (9%) registered by us in the median follow-up of 575
      days (range 105-1118 days) was much higher than that seen in older infants.
      Nevertheless, based on the low perioperative complication rate registered in the
      present study, we postulate that early surgery is tenable in pre-term infants
      despite the high co-morbidity and is even meaningful for the purpose of reducing
      the high rate of incarceration and testicular atrophy. The high recurrence rate
      in pre-term infants appears to be related to the numerous concomitant diseases in
      these patients, the resultant increase in intra-abdominal pressure and the small
      size of anatomical structures.

PMID- 11505657
TI  - Bubo masquerading as an incarcerated inguinal hernia.
AB  - A 44-year old, male, tattooed, leather jacket clad, Harley-Davidson motorcyclist
      arrived at the emergency room with a tender, irreducible mass, presenting at the
      external inguinal ring. In 1998, lung biopsy was read as miliary granuloma. No
      herniation was found on urgent preperitoneal exploration. Incision of the mass
      showed acid-fast bacilli. Culture later revealed Mycobacterium avium
      intracellulare (MAI). A blood count showed CD4 lymphopenia; HIV was negative and
      remains so 2 years later.

PMID- 11505658
TI  - Abdominal-wall pseudohernia secondary to herpes zoster.
AB  - We present a case of a 78-year-old woman with abdominal-wall muscle paralysis
      following cutaneous herpes zoster in the T12-L1 dermatomes. An EMG confirmed
      paralysis, and a CT scan ruled out fascial defect. The paralysis had completely
      resolved 1 year later. A review of the literature regarding these unusual
      sequelae of herpes zoster is presented.

PMID- 11505659
TI  - ["Abdominal" variant of myocardial infarction: clinical features and diagnostic
      errors at the prehospital stage].
AB  - The results of prehospital diagnosis of myocardial infarction (MI) were studied
      in 1500 patients. The onset of MI was abdominal, gastralgic, and dyspeptic in
      1.7, 1.3, and 0.4%, respectively. Abdominal MI differed from typical (anginal) MI
      in the relative predominance of old patients and women, late referrals to
      doctors, a high incidence of large and primary MI, worse prognosis. Hospital
      mortality in anginal and abdominal MI was 13.9 and 50.0% (p < 0.01),
      respectively. The rates of untimely diagnosis of anginal and abdominal MI were
      13.4 and 25.0% and those of hyperdiagnosis were 19.9 and 31.8%, respectively.
      Prognosis in the hypodiagnosis of abdominal MI was worse than that in its
      hyperdiagnosis.

PMID- 11505660
TI  - [Correction of mitral valve insufficiency in the incomplete form of
      atrioventricular canal].
AB  - Correction of the incomplete atrioventricular canal is considered to be a routine
      operation leading to mortality no more than 5%. Significant insufficiency of the
      atrioventricular (AV) valve worsens prognosis and increases mortality up to 30%.
      From 1989 to 1999 the Research Center of Cardiovascular Surgery performed 151
      operations for this defect in patients aged 3 months to 50 years, which showed
      general mortality rates of 8.6%. The latter were largely related to the baseline
      insufficiency of the left AV-ostium, to the patientsT age of patients and the
      year of an operation. A combination of reparative valvuloplasties permits one to
      restore obturative mitral function more completely and to improve the outcomes of
      defect correction. Significant insufficiency of the AV-valve (over ++) is a risk
      factor of its preservation after surgery and may lead to death. Consideration of
      adequate indications for primary valve prosthesis may substantially reduce
      mortality rates.

PMID- 11505661
TI  - [Reconstructive operations in combined burn strictures of the esophagus and
      stomach].
AB  - Variants of surgical repair for patency of the esophagogastroduodenal tract, used
      in the treatment of 64 patients with combined burn strictures of the stomach and
      esophagus are presented. The scope of reconstructive operations depended on the
      patientsT baseline status, the severity of concomitant diseases, the pattern of
      anatomical disorders of burned organs. In short distal burn strictures of the
      esophagus and stomach, esophagogastrostomy and gastroduodenostomy were performed
      (2). If the burn stricture was in the pyloric area, pyloroplasty was performed
      (9). In patients with antral and pyloric stenoses, gastroduodenal anastomosis was
      formed (3). If burn damage to the stomach could not be clearly differentiated,
      gastroenterostomy was made. If there were scars in the stomach, it was respected
      by one of BillrotTs methods (30). Only in 8 of the 64 patients reconstructive
      operation on the stomach could be combined with esophagoplasty and in 4 cases
      stepwise esophagoplasty was performed by transpositing a small intestinal graft
      to the neck. Esophagoplasty was made with a fragment of the ileocolon in 32
      patients, with that of the left half of the colon in 23, one and 6 patients
      underwent intrapleural and small intestinal esophagoplasty, respectively.
      Esophagoplasty with local tissues was performed in 2 patients. Postoperative
      mortality was 6.25%.

PMID- 11505662
TI  - [Surgical treatment of perforated gastroduodenal ulcers].
AB  - Experience in surgically treating 820 patients aged 15 to 83 years who had
      perforated gastroduodenal ulcers is summarized. In 576 (70.2%) patients the
      perforated hole was sutured. Thirty-four (4.2%) patients underwent gastrectomy
      and 210 (25.6%) had vagotomy with drainage operation on the stomach. After
      surgery 39 (5.6%) patients died. Mortality rates after ulcer suturing,
      gastrectomy, and vagotomy with gastric drainage were 6.2, 2.7, and 0.9%,
      respectively. Recurrent ulcer occurred in 57.3% after ulcer suturing, in 2.9%
      after gastrectomy, and in 9% after gastric drainage vagotomy. By taking into
      consideration the high rate of recurrent ulcers following palliative
      interventions, the author proposes to expand indications for radical surgery in
      patients with serous and serofibrinous forms of general peritonitis in the
      reactive phase.

PMID- 11505663
TI  - [Treatment of perforated gastroduodenal ulcers].
AB  - Results of treatment of 751 patients with perforated gastroduodenal ulcers are
      analyzed. In addition to routine tests, ultrasonography, computed tomography and
      laparoscopy were used to diagnose difficult cases. The optimum surgical aids are
      chosen by taking into account the interval between the onset of perforation and
      admission, a history of peptic ulcerous, the pattern of peritonitis, age,
      comorbidity, and surgical findings. Organ-saving operations with a vagotomy are
      preferable. 1% serotonin-adipinate (1 ml dissolved in 200 ml saline solution) was
      intravenously used to prevent early postvagotomic disorders (gastric atony,
      dynamic ileus, etc.) in the early postoperative period. Organ-saving operations
      with vagotomy were found to have some advantage over routine suturing.

PMID- 11505664
TI  - [Current problems of the surgical treatment of uncomplicated duodenal ulcer].
AB  - How to choose treatments for uncomplicated duodenal peptic ulcer is discussed.
      The data available in the literature suggest that there is a high incidence of
      recurrent ulcers even after regular. This is evidenced by experience in examining
      and treating 1414 patients at the Institute of Surgery. A large number. The
      authors consider a great deal of patients to be unresponsive to drug therapy, in
      whom the disease is characterized by frequent recurrences and complications.
      These patients require organ-saving surgical treatment. Selective proximal
      vagotomy that present the minimum risk is the operation of choice. A five-year
      follow-up revealed 21.4% of recurrences, which effectively responded to drug
      therapy. This rate is much less than that observed after drug therapy alone.

PMID- 11505665
TI  - ["Difficult" duodenal stump in emergency surgery of duodenal ulcer].
AB  - Analysis of surgical prophylactic measures of sutures insufficiency of difficult
      duodenal stump in stomach resection by Bilrot-II in 110 patients with
      complications of duodenal ulcers required urgent surgery are presented. In study
      group (43 patients) complex approach to surgical prophylactic measures including
      diagnosis and correction of chronic disorders of duodenal passability (revealed
      in 69.8% cases) and individualization of suturing method of duodenal stump was
      used. In control group (67 patients) traditional external drainage of stump was
      used as a main prophylactic measure in high risk of complications, method of
      stump treatment was not individual. Suture insufficiency of duodenal stump was
      revealed only in control group in 10.4% (7 patients) with 57.1% mortality (4
      patients died). General lethality in Group 1 was 4.7% (2 patients), in 2nd--13.4%
      (9 patients), 6% operated of them died due to insufficiency of duodenal stump. In
      the structure of death causes, duodenal stump suture incompetence heads the list
      (44.4%).

PMID- 11505666
TI  - [Abnormalities of the pericardium].
AB  - By 2000 there have been at least 187 cases of rare pericardial malformations (of
      them there were 5 cases of the authors) and 1047 cases of celomic pericardial
      cysts (CPC) (43 cases of the authors) in the literature. Of them 18 (9.6%)
      patients were found to have no pericardium, the absence of its left half was in
      76 (40.6%). No left pericardium was more common in men (61.04%) than in women
      (38.96%). The literature reports about the absence of the right pericardium only
      in one case. Partial pericardial defects were encountered in 30.48% of patients
      with rare pericardial malformations. In general, malformations in the left
      pericardium were 10 times more common often than those in the right one. The
      absence of the pericardium or its half most commonly requires no surgical
      correction. In partial defects, suturing or plastic closure must be performed due
      to a risk for strangulation and a possible fatal outcome. CPC are not clinically
      manifested in more than 50% of the patients with CPC, but in some cases dyspnea,
      dry cough, palpitation may be caused by other causes. Cystectomy yields good
      results.

PMID- 11505667
TI  - [Rehabilitation of operated patients with diffuse polyposis of the large
      intestine].
AB  - In 1965 to 2000, the State Coloproctology Research Center operated on 584
      patients for diffuse polyposis of the large intestine. A 18-year follow-up showed
      that metabolic disorders developed in 85% of cases due to the loss of large
      intestine that is important for maintaining homeostasis. The authors consider it
      necessary to continuously follow up the patients operated on for diffuse
      polyposis for timely diagnosis of occurring metabolic disorders and their
      correction. This approach to complex treatment of diffuse polyposis promotes
      social and working rehabilitation of patients operated on.

PMID- 11505668
TI  - [Technical aspects of the use of TakhoKomb in surgery of abdominal organs].

PMID- 11505669
TI  - [Injuries of the duodenum during laparoscopic surgery].

PMID- 11505670
TI  - [Stomach cancer after coronary bypass using the right gastro-omental artery].

PMID- 11505671
TI  - [A rare cause of chronic duodenal obstruction].

PMID- 11505672
TI  - [Heterotopia of the pancreas in the stomach].

PMID- 11505673
TI  - [Adjuvant therapy of breast cancer].

PMID- 11505675
TI  - [2001 calendar of memorable dates in the history of surgery].

PMID- 11505674
TI  - [Academician Nikolai Nilovich Budrenko (the 125th anniversary of his birthday)].

PMID- 11505676
TI  - Comparative analysis of DNA content estimated by flow and image cytometry in
      breast tumor samples.
AB  - The DNA ploidy status of 186 fresh primary breast tumors was analyzed in a
      comparative study of flow cytometric (FCM) and image (IA) analyses. Tumor size,
      histology and nodal status were also taken into account. The same piece of fresh
      tissue was used for touch imprints (IA) and for DNA analysis by FCM. Both methods
      provided concordant DI values in 158 (85%) tumors (r = 0.7490). The tumor grade
      and lymph node status significantly correlate with ploidy estimated by FCM and
      IA. We conclude that FCM and IA provide comparable results of DNA content
      although occasional discrepancies occur. IA seems to be a more sensitive method
      especially for diploid cases detected by FCM.

PMID- 11505677
TI  - Expression of HER2/neu in primary and metastatic breast cancer.
AB  - The study was performed for answering the question whether metastatic breast
      cancer has the same overexpression of HER2/neu as primary breast tumor. We
      assumed that study on this subject could give a valuable information for proper
      interpretation of HER2/neu overexpression in breast cancer patients designated
      for therapy with Herceptin. Our study was performed on 71 breast cancer patients
      qualified for clinical trial with Herceptin therapy. All patients selected for
      this trial have had surgery and two episodes of unsuccessful adjuvant therapy.
      Tissue samples were routinely fixed in 4% formalin and embedded in paraffin.
      Immunohistochemical assays were performed on 5 microns slides using DAKO
      HercepTest and semi-quantitative methods to determine HER2 protein overexpression
      were used. All study cases were subdivided into two groups. First group--49 cases
      in which expression of HER2 was examined in tissue from primary breast tumors,
      and second group--22 cases in which expression of HER2 was examined in tissue
      from metastatic lesions. In the whole study group (71 cases) overexpression was
      confirmed in 29 (40.8%) cases. In the group of primary breast tumors
      overexpression of HER2 was present in 20 (40.8%) of cases. In the group of
      metastatic breast tumors overexpression of HER2 was present in 9 (40.9%) of
      cases. The result suggests that overexpression which appears in primary breast
      carcinoma is also preserved in metastases. Direct prove of such a conclusion,
      would be a study on HER2/neu expression estimated in primary and metastases in
      the same patients. It requires a proper quantity and quality of material. Our
      results indicate that there is no difference between the estimation of HER2/neu
      overexpression in primary and metastatic breast cancer in patients with
      disseminated disease after double failure of chemotherapy. Evaluation of
      overexpression of HER2/neu in cases of planned Herceptin therapy can be done both
      in material from primary and from metastatic tumor.

PMID- 11505678
TI  - The application of electron microscopic morphometry as helpful method in the
      diagnosis of focal segmental glomerulosclerosis (FSGS) early phase. I.
      Morphometric electron microscopic studies of renal glomeruli in cases of focal
      segmental glomerulosclerosis (FSGS), minimal change disease (MCD) and
      mesangioproliferative glomerulonephritis (GNMES) in children.
AB  - Electron microscopy morphometric studies were carried out on material obtained
      from children with minimal change disease (MCD), mesangioproliferative
      glomerulonephritis (GNMES) and focal segmental glomerulosclerosis (FSGS). The
      results indicated that an increase in the volume of the matrix in
      mesangioproliferative glomerulonephritis was due to an increase in the number of
      cells. The amount of produced matrix in mesangioproliferative glomerulonephritis
      was proportional to the number of cells in mesangium (so there is no
      overproduction of matrix). The ratios of mesangial matrix volume to cell volume
      and matrix volume to the volume of the entire mesangial region in MCD and GNMES
      were similar and differed significantly from the ratios found in FSGS. The
      present findings indicate that morphometric studies may be useful in the early
      diagnosis of glomerular sclerosis. This is particularly significant in cases
      where light microscopic examination fails to reveal changes indicative of
      glomerular sclerosis.

PMID- 11505679
TI  - The application of electron microscopic morphometry as a helpful method in the
      diagnosis of focal segmental glomerulosclerosis (FSGS) early phase. II. Clinical
      usefulness of electron microscopic morphometric studies in cases of minimal
      change disease (MCD) and mesangioproliferative glomerulonephritis (GNMES) with
      suspicion of progression into focal segmental glomerulosclerosis (FSGS).
AB  - Clinical and morphological analysis (including morphometric studies of electron
      microscopic material) was made in 15 children with MCD and 15 children with
      GNMES. In both groups, an early phase of FSGS was suspected on the basis of
      electron microscopic studies. Moreover, analysis included the results obtained in
      13 children with the diagnosis of FSGS and in whom repeated biopsies were
      performed. In most of them, MCD or GNMES was diagnosed from the first biopsy. In
      most children in whom electron microscopic studies revealed an increase in matrix
      area in some mesangial regions, thereby suggesting an early stage of glomerular
      sclerosis, the results of morphometric studies resembled or were identical to the
      results obtained from a control group with the established diagnosis of FSGS.
      These findings indicate that morphometric studies of electron microscopic
      material are significant. The results, when compared with the clinical data,
      confirm the usefulness of such a diagnostic procedure.

PMID- 11505680
TI  - Clinico-pathological analysis of pilocytic astrocytomas and gangliogliomas.
AB  - A pathological analysis of 58 pilocytic astrocytomas (PA) and 11 gangliogliomas
      (GG) was performed using immunohistochemistry. Antibodies against neuronal and
      glial markers (GFAP, SYN, NFP) were used. An analysis of survivors using the
      Kaplan Meier curve was also performed and compared with the literature reports.
      During the retrospective review of 58 cases recognized primarily as PA, 11
      verified neoplasms demonstrated strong, immunopositive reaction for SYN or NFP or
      both antibodies. These cases were reclassified as gangliogliomas (GG). None of
      the 11 tumors recognized as GG was reclassified as PA. The overall 5-year
      survival was 88.89% in the PA and 70% in GG groups.

PMID- 11505681
TI  - The comparison of immunohistochemical proliferation and apoptosis markers in
      rectal carcinoma treated surgically or by preoperative radio-chemotherapy.
AB  - The aim of the study was to determine prognostic histopathological and
      immunohistochemical factors expressed by proliferation and apoptosis markers in
      patients treated only surgically or by preoperative radio-chemotherapy. The
      material was obtained from 204 patients; 114 patients underwent an operation, 35
      patients had preoperative radiotherapy (2500 cGy in 5 fractions for 5 days) and
      55 patients were treated with preoperative radio-chemotherapy (5000 cGy in 25
      fractions for 33 days and 3 courses of chemotherapy 5Fu and Leucovorin). In 204
      cases the operative material was examined taking into account: 1. the age, sex,
      size of tumor, macroscopic features, stage, angioinvasion and perineural
      invasion, 2. cancer response to the treatment, 3. immunohistochemical factors
      being the expression of p53, MIB1, bcl-2, bax. In additional, a statistic
      analysis was carried out using chi-square test and NW method to examine
      individual parameters and Spearman (R) rank correlation to define the force of
      dependence. RESULTS: 1. In cases of colorectal cancer treated only surgically,
      statistically significant correlations occurred among the stage, angioinvasion
      and perineural invasion. 2. The partial response with regression of the tumor
      mass less than 2/3 occurred in 90% of patients after short radiotherapy. The
      complete response (CR) was seen in 15% of cases, the regression of the tumor mass
      more than 2/3 (PR1)--in 46% of cases and the regression of the tumor mass less
      than 2/3 of (PR2)--in 39% of cases after preoperative radio-chemotherapy. 3. A.
      In biopsy taken in 27 patients before radio-chemotherapy expression of MIB1 and
      bax proved to be statistically significant. The low expression of MIB1 and the
      high level of bax expression were correlated with the total or near-total
      response of cancer to the treatment. B. In operative material after radio
      chemotherapy a statistically significant dependence occurred among all
      immunohistochemical markers; regression of the tumor mass less than 2/3
      correlated with the low expression of p53, MIB1, bax and bcl-2. 4. The force of
      dependence among immunohistochemical parameters in patients only after surgical
      treatment was R = 0.2-0.3 and after radio-chemotherapy R = 0.8. CONCLUSION: The
      expression of proliferation and apoptosis markers was combined with rectal
      carcinoma after preoperative radio-chemotherapy.

PMID- 11505682
TI  - Sporadic fundic gland polyps, GERD and omeprazole usage: is there a little piece
      of information missed?

PMID- 11505683
TI  - Current problems in clinico-morphological assessment of soft tissue tumors.
AB  - Soft tissue tumors differ in their histology and biological behavior.
      Irrespectively of changing classification, different grading and staging systems
      of these lesions are based on similar characteristics and are of comparable
      clinical value. Electron microscopy, immunohistochemistry and particularly
      molecular biology facilitate their diagnosis, identification of new tumor
      entities and provide indicators for their prognosis and strategy of treatment.
      The new treatment modalities demand tumor characterisation before surgery,
      whereby sampling of tumor material is of special importance. Fine needle
      aspiration biopsy, apart of its limitations, is of special value in pre-treatment
      assessment of soft tissue tumors. Diagnosis and treatment of soft tissue tumors
      should be performed in cooperation between clinicians and representatives of
      diagnostic disciplines.

PMID- 11505684
TI  - [Occlusion of a post-pneumonectomy bronchopleural fistula using the Dumon stent].
AB  - A postoperative bronchiopleural fistula associated with empyema of the chest is a
      serious complication in thoracic surgery, in particular when it develops after
      pneumonectomy. Some patients are in a condition which threatens their life and
      rules out extensive surgical interventions. Immediate thoracic drainage,
      thoracoscopic revision and sanation of the empyema cavity and endoscopic closure
      of the fistula are in indicated cases a therapeutic alternative of open surgical
      procedures. The justification of these miniinvasive procedures is confirmed by
      the submitted case-record of a successfully cured fistula associated with empyema
      of the chest after pneumonectomy. At the same time, based on assembled
      experience, the authors draw attention to the possible use of a stent.

PMID- 11505685
TI  - [A universal stereotactic device for spinal cord surgery].
AB  - Technical description of a universal stereotactic system for spinal cord
      operations is presented after a short overview of the history of spinal cord
      stereotaxis. When combined with the topometric atlas of the cord, new era of
      spinal cord stereotaxis can be opened, which is going to expand the amount of
      knowledge about the physiology of the spinal cord.

PMID- 11505686
TI  - [A large ovarian teratoma mimicking acute abdomen--case report].
AB  - Authors present case report of an adolescent girl with the large ovarian
      teratoma. Teratoma of the ovary was surprising finding during laparotomy which
      was indicated on the basis of acute abdomen. Tumorectomy was performed.
      Microscopic examination revealed differentiated mature teratoma. There were no
      signs of recurrence. Authors present short review of the literature concerning
      this rare diagnosis and the reason of acute abdomen.

PMID- 11505687
TI  - [Enteral nutrition in clinical surgical practice].
AB  - The authors present their clinical experience with enteral nutrition in 108
      surgically and conservatively treated surgical patients in 1998-2000. The use of
      combined enteral and parenteral nutrition in different indications led to
      improvement of the nutritional status of patients with all consequences and at
      the same time it had a positive impact on the economic balance of the surgical
      department. As the ideal solution seems perioperative nutrition combined with
      postoperative enteral nutrition. Enteral nutrition can be however used also in
      conservatively treated patients. In the group there were no serious complications
      and the percentage of undesirable effects did not exceed data reported in the
      literature.

PMID- 11505688
TI  - [Rubber band ligation of hemorrhoids in ambulatory care].
AB  - OBJECTIVE: The aim of the study was to evaluate the outcome of elastic ligation
      in internal haemorrhoids in our out-patient setting. METHODS: The authors
      performed elastic ligation of haemorrhoids in 77 patients, and of these 71 (92%)
      procedures were accomplished in out-patients. The procedure was indicated in
      second and third-degree symptomatic haemorrhoids and was carried out without
      local anaesthesia with the aid a Seward Medical applicator. Typically, one
      haemorrhoidal node was treated per one session. All patients were clinically
      examined two weeks after completion of treatment. RESULTS: The success rate of
      the procedure was 91%. The results were analyzed by a questionnaire. The most
      common unpleasant symptoms were pain and tenesms. Bleeding occurred in 6
      patients. There was no serious life-threatening complication. CONCLUSION: Based
      on our observation we consider band ligation as a reliable therapy for
      symptomatic internal haemorrhoids in out-patients. We suggest reminding patients
      of possible of complications, unpleasant symptoms sensations restricting their
      daily activity on the first days after the procedure.

PMID- 11505689
TI  - [The urinary tract in graft recipients and urologic complications after kidney
      transplantation].
AB  - BACKGROUND: Urological complications after renal transplantation condition reduce
      graft survival and function. It may be assumed that an important part, in
      addition to technical factors during removal and implantation of the organ may be
      played also by factors of the recipient. The authors investigated whether in the
      development of some urological complications (urinary fistulae and urinary tract
      dilatation) also pathological changes of the urinary tract of the recipient,
      kidney diseases leading to renal failure or the development of urinary flow rate
      during the first days after transplantation of the kidney participate. METHODS
      AND RESULTS: The authors investigated 77 patients after renal transplantation
      where during the period from Jan. 1992 till Dec. 1996 a urinary fistula developed
      (42 cases), dilatation of the urinary tract (32) or both complications (3). The
      control group was formed by 100 patients without urological complications who did
      not differ as to demographic data, basic immunosuppressive treatment and who had
      transplantations during the same period and by the same surgical techniques. The
      assembled data were evaluated statistically, the two groups being compared by
      means of t-test, chi 2 test and the non-parametric Mann-Whitney test resp. The
      authors investigated factors which might participate in the quality of the
      recipient urinary tract, in particular the recipient's age. In the group of
      urologically complicated cases there were significantly (p < 0.05) more patients
      above 55 years. There were also more males (67.5% vs. 32.5%, p < 0.05). In
      further factors such as the ratio of BMI ratio or the underlying kidney disease
      leading to renal failure and the presence of diabetes mellitus the authors did
      not record significant differences. The residual urinary flow rate, duration of
      dialysis treatment before transplantation and the number of transplantations did
      not differ significantly. The authors tried to evaluate the possible influence of
      urinary flow rate on the development of urological complications after
      transplantation of the kidney. CONCLUSIONS: The assembled findings support the
      idea that the development of a urinary fistula or dilatation of the urinary tract
      were not significantly influenced by changes in the urinary tract of the
      recipient conditioned by the period of the reduced function, as may be assumed on
      the basis of the time of dialysis treatment. The development of the investigated
      urological complications was not significantly influenced by the presence of
      underlying kidney diseases nor by increased urinary flow rate during the first
      days after transplantation. The authors did not confirm the risk of re
      transplantation. An significant effect on the development of urological
      complications could be exerted by male sex and age above 55 years.

PMID- 11505690
TI  - [Comparison of 2 methods of diagnosis of changes in transplanted kidneys in the
      early postoperative period: biopsy vs dynamic scintigraphy of the graft].
AB  - Renal transplantation is at present a standard therapeutic method in chronic
      renal insufficiency. For a favourable development of the graft some investigated
      criteria are of basic importance: basic diagnosis which led to renal failure,
      period of dialyzation treatment, high standard collection and perfusion and early
      diagnosis of the rejection episode. Non-invasive diagnostic methods of the
      rejection episode are always indirect and correlate with histologically confirmed
      rejection, depending on the period of transplantation in 10-90% patients.
      Indirect diagnosis is based in particular on a rise of the creatinemia, decline
      of glomerular filtration, fluid retention variations of blood pressure and
      increase of the Doppler assessed index of resistance (IR) in the peripheral veins
      of the graft [1]. For many years the role of nuclear diagnostics are tested. The
      disadvantage of direct diagnosis--biopsy--is increased haemorrhage and loss of
      the graft [1, 2, 3, 4]. The greatest problem is the differentiation of acute
      (cellular) rejection as compared with acute tubular necrosis during the initial
      days after transplantation. The authors describe their experience with 81
      biopsies in the course of 3 years in patients during the first 10 days after
      transplantation, comparison with dynamic scintigraphy of the graft. Their
      attention is focused on the technique and risks of renal biopsy.

PMID- 11505691
TI  - [Aspergillosis--a rare complicating disease in patients after renal
      transplantation].
AB  - The authors submit a detailed analysis of the death of a 42-year-old man after a
      second renal transplantation. The patient died with symptoms of cardiac failure
      in a septic condition of obscure etiology where even detailed examination did not
      provide a timely answer as regards the lethal pathogen. Aspergillus fumigatus is
      a rare lethal pathogen. Despite this it is, as all opportune infections, for
      patients with immunosuppressive therapy a serious life threatening infection [1,
      2]. In a group of 650 transplantations performed since 1961 in Hradec Kralove it
      is the first death caused by generalized Aspergillus infection.

PMID- 11505692
TI  - [Primary retroperitoneal seminoma].
AB  - The case-history presents a case of a rare retroperitoneal tumour--primary
      retroperitoneal classical seminoma. This type of tumour accounts for half the
      extragonadal germinal tumours. From the clinical aspect this group is important
      as in addition to surgery it can be successfully treated by chemotherapy and
      radiation. The clinical findings in the authors' patient led to the diagnosis of
      a retroperitoneal tumour and after repeated examinations the authors concluded on
      the presence of some form of malignant mesenchymal tumour. A more aggressive
      surgical procedure implies radical removal of the tumour, and treatment was,
      based on the final histological diagnosis, supplemented by chemotherapy. Despite
      the favourable diagnosis of seminomas, we have to foresee in case of a primary
      tumour in the retroperitoneum a poorer prognosis (sometimes by as much as 50%)
      and despite all conclusions attention should be devoted to a possible late
      development a testicular tumour.

PMID- 11505693
TI  - [Total thyroidectomy as the most frequent surgical procedure on the thyroid
      gland].
AB  - In 1997 and 1999 at the Second Surgical Clinic 35 patients with thyroid disease
      were operated. The authors reflect on the increasing radicality of operations
      from the aspect of the endocrinologist and surgeon. Extended surgical operations
      in relation to the original endocrinological indications are explained by the
      surgical finding and results of the histological examination.

PMID- 11505694
TI  - [Snoring and excessive daytime somnolence and risk of cardiovascular diseases].
AB  - Snoring and excessive daytime somnolence (EDS) are very common in middle-age
      adults. The goal of the investigation was to assess links between those symptoms
      and risk for cardiovascular diseases (CVD). The population studied included 1186
      inhabitants of Warsaw (mean age 52 years), participants of the international
      multicentre study of cardiovascular disease MONICA II, who completed the sleep
      disordered breathing (SDB) questionnaire. Snoring was reported by 78% of males
      (48% habitual and 30% occasional) and 59% of females (27% habitual and 32%
      occasional). Every fourth (26.8%) subject declared observed apnoeas, in 9.2%
      apnoeas were observed every night. EDS was declared by 28.7% of studied sample.
      The results of the questionnaire were compared to the results of MONICA study.
      Snorers had significantly higher systolic and diastolic blood pressure (133.2 +/-
      23/84.6 +/- 13 mm Hg) compared to non-snorers (126.4 +/- 22/80.4 +/- +/- 12 mm
      Hg) (p < 0.0001). The high total serum cholesterol (> or = 200 mg%) and
      triglycerides (> or = 200 mg%) concentration, and also obesity (BMI > or = 30
      kg/m2) were more prevalent in snorers. Subjects reporting apnoeas more often had
      coronary artery disease (p < 0.001) or history of stroke (p = 0.002) compared to
      non-apnoeics. There was no relationship between EDS and risk of cardiovascular
      disorders, and also between diabetes and SDB. In conclusion, snoring was strongly
      associated with hyperlipidaemia, obesity or hypertension, well known risk factors
      for development of cardiovascular disorders. Reported apnoeas were related to
      risk of coronary artery disease.

PMID- 11505695
TI  - [Selected parameters of antioxidant capacity in renal allograft recipients].
AB  - Various oxidant species, oxygen free radicals (OFR) implicated in patients with
      chronic renal diseases treated with dialysis and after cadaveric renal
      transplantation. Oxidative stress occurs when free radical generation exceeds
      antioxidant defence. We therefore examined markers of lipid peroxidation and
      antioxidant potential in blood (serum, plasma, RBC) of very carefully (clinically
      and biochemically) selected 102 subjects (56 female and 46 male, mean age 37.5 +/
      7 years). Included were 51 renal allograft recipients (RARs); 15 patients with
      glomerulopathies (GL); 36 healthy age- and sex-matched volunteers as a control
      group (C). All RARs were divided into two subgroups: RARs-A (n = 28) were treated
      with triple drug therapy including cyclosporin A (CsA) and RARs-Z (n = 23) were
      on double drug regimen: prednisone, azathioprine. Patients with coronary artery
      disease (CAD), diabetes, serum creatinine concentration > 2.0 mg/dl, acute
      rejection and infections were excluded. We used several automated assays to
      estimate: malondialdehyde (MDA); total radical-trapping antioxidant potential
      (TRAP), glutathione peroxidase (GPx), glutathione (GSH), superoxide dismutase
      (SOD), catalase (CAT), vit. E and lipid profiles. Patients of RARs-A were found
      to have significantly elevated triglycerides; cholesterol-LDL; MDA; TRAP and
      decreased activity of RBC glutathione peroxidase as compared with those of RARs-Z
      and group C. IN CONCLUSION: our data show that oxidative stress (with prooxidant
      effect of CsA partly at least), with reduced in antioxidant potential of defences
      system is associated with kidney transplantation.

PMID- 11505696
TI  - [Reduction of the plasma LDL-cholesterol level among young healthy men as a
      result of the change from butter to soft margarine in the unbalanced diet].
AB  - The aim of the study was to evaluate the level of lipid profile on 83 healthy
      males consuming soft type margarine instead of butter, in their unbalanced diet.
      For this purpose double blind, cross-over methodology was applied. After
      stabilization period of consuming the diet, the whole sample was randomly divided
      into two subgroups (A n--37; B n--46). First group was consuming 15 g of the
      butter twice a day (30 g in total) and the second identically packed soft type
      margarine (also twice a day 15 g; 30 g in total) containing high level (33.3
      g/100 g) of polyunsaturated fatty acids. After four weeks, the diet of subgroups
      was mutually exchanged--group consuming margarine consumed butter and the
      opposite. The feeding pattern of both groups was monitored with the aid of FOOD 2
      computer programme. The group under investigation consisted of healthy males at
      the age 23.3 +/- 2.5, BMI 24.4 +/- 3.9 kg/m2; WHR 0.82 + -0.06 and normal blood
      pressure. Exchange of butter into soft margarine caused the increase of P/S ratio
      from 0.30 to 0.78 in their diet. Both investigated groups shoved average decrease
      of 10.7% of blood cholesterol content (in group A 13.8%), LDL cholesterol of
      about 9.8% and triglycerides ca 12.7% (higher decrease in group B--16.7%). Both
      groups while on margarine diet shoved small decrease of HDL cholesterol (3.9%).
      It can not be the matter of serious concern due to average HDL content in both
      groups was ca 52 mg/dl (ca 1.4 mmol/l)--it means considerably excessive the
      limited risk (35 mg/dl; 0.90 mmol/l). Application of the margarine diet in group
      A caused the decrease the ratios of total cholesterol to HDL cholesterol from
      3.84 into 3.52; whereas in group B from 4.15 into 3.75. It was also concluded,
      that the low trans isomer margarine show no effect on lipoprotein Lp(a). Back to
      the diet with butter after 4 weeks carry down the beneficial effects of diet with
      margarine on lipid profile. The results indicate that for lipid profile the
      consumption of soft margarine was more beneficial than butter, even for
      unbalanced diet.

PMID- 11505697
TI  - [Influence of Chlamydia pneumoniae and cytomegalovirus infections on prevalence
      and the course of coronary artery disease].
AB  - Chlamydia pneumoniae (C. pneumoniae) as well as cytomegalovirus (CMV) are common
      pathogens found in about 50% of healthy western population. Many studies suggest
      a role of C. pneumoniae in development of coronary artery disease (CAD). CMV
      infection is also considered to increase risk of developing of CAD as well as
      restenosis after percutaneous coronary revascularization (PCI). The aim of our
      study was to evaluate a possible role of C. pneumoniae and CMV infections in both
      CAD development and course in patients (pts) undergoing PTCA. We enrolled 105 pts
      (mean age 56.4 years, 83 males) with angiographically documented CAD. Control
      group consisted of 63 healthy controls (mean age 47.25 years; 31 males). The
      study subjects were evaluated for presence of C. pneumoniae specific IgG
      antibodies (MIF test--MRL Diagnostic, USA; seroprevalence assumed when titre > or
      = 1/8). In 58 random PCI pts CMV specific IgG antibodies (ELISA Eti-Cytok-G PLUS-
      Dia Sorin) were evaluated. Pts were sampled at the time of PTCA. All PCI pts were
      assessed by angina questionnaire 5.9 +/- 2.6 months (mo) after the procedure with
      respect to clinical restenosis. C. pneumoniae IgG antibodies were detected in
      37.1% of pts and in 22% of healthy controls (p < 0.05). After logistic regression
      was applied trend towards more frequent occurrence of C. pneumoniae specific IgG
      in CAD pts was shown (p = 0.10 OR = 2.4; 95% CI: 0.8-6.8). No significant
      correlation was found between anti-C. pneumoniae IgG presence or anti-CMV IgG
      titre and coronary atherosclerosis advancement. There was no significant
      difference in anti-CMV IgG titre between 9 pts who developed clinical restenosis
      5.9 +/- 2.6 mo after PCI and the remaining pts. Our study results suggest a
      possible significant correlation between C. pneumoniae with CAD prevalence. We
      did not find a positive association of either infection markers with coronary
      atherosclerosis advancement. We did not find correlation of clinical restenosis
      after PCI with markers of CMV infection.

PMID- 11505698
TI  - [Adenine reutilization as a cause of increased ATP concentration in erythrocytes
      of patients with chronic renal failure].
AB  - Abnormalities of adenine nucleotide metabolism are observed in erythrocytes of
      patients with chronic renal failure (CRF) and the elevated ATP concentration is
      the most impressive one. In humans, adenine and/or adenosine reutilization is the
      only source of purine moiety used to erythrocyte adenine nucleotide synthesis. In
      the present study we have focused on the role of adenine as a substrate for the
      intraerythrocyte ATP production. 10 patients with CRF and 10 healthy volunteers
      (control group) were included into the study. Using HPLC, the measurements were
      performed in plasma and erythrocyte extracts. We observed a few fold higher
      adenine concentration in both plasma and erythrocytes of patients with CRF when
      compared with control group. There was also elevated an intraerythrocyte ATP
      concentration in the studied group of patients. Moreover, we have found a
      positive correlations between a) plasma creatinine concentration and plasma
      adenine concentration, b) plasma creatinine concentration and erythrocyte adenine
      concentration, c) plasma adenine concentration and intraerythrocyte ATP
      concentration. It appears that increased adenine reutilization could be a
      principle reason of the increased ATP synthesis in erythrocytes of patients with
      CRF.

PMID- 11505699
TI  - [Differences of the clinical course and prognosis in diabetics with myocardial
      infarction].
AB  - Diabetes mellitus (DM) is one of the most potent risk factor of in-hospital and
      long-term prognosis after myocardial infarction (MI). The study aim was to
      compare in-hospital management and long-term prognosis in diabetics with acute
      transmural MI especially in the aspect of thrombolytic therapy. We analyzed 881
      patients with acute MI treated in our hospital in 1992-1996. DM was found in
      21.5% of all studied patients. Data based on past history, management of in
      hospital course and next ambulatory control exams in the period 2-6 years were
      performed using statistical methods and then compared together. Diabetics had
      significant more often risk factor of development of coronary artery disease.
      Thrombolytic therapy had received 18.0% of diabetics and 22.1% nondiabetic
      patients in the age under 80 years-old. Thrombolytic therapy performed at
      patients with DM significantly reduced in-hospital mortality. CONCLUSIONS: 1.
      Diabetics had worse in-hospital course of acute MI because of more frequent
      hemodynamic complications. The overall incidence of arrhythmia and A-V conduction
      disturbances did not differ from nondiabetics. 2. In-hospital mortality in all
      patients with DM was twofold higher than in the rest (22.2% vs 11.0% p < 0.001).
      Mortality among patients with thrombolytic therapy did not significantly differ
      between the ones (5.9% vs 6.7%). 3. Mortality rate after MI in diabetics is 1.66
      times higher to compare to nondiabetic.

PMID- 11505700
TI  - [Pulmonary manifestations of polymyositis and dermatomyositis: a report of 6
      cases and a review of literature].
AB  - The group of 6 patients with interstitial pulmonary changes in the course of
      polymyositis or dermatomyositis treated in years 1986-1999 was assessed. In one
      woman pulmonary changes occurred ten years before other symptoms of the
      connective tissue disease. Lung function tests showed a restrictive ventilatory
      defect in all patients. High resolution computed tomography revealed different
      changes, from ground glass attenuation to honey--combing. Only one patient,
      probably with bronchiolitis obliterans organizing pneumonia, responded to
      corticosteroids. Four women died from respiratory failure. In 2 pneumomediastinum
      occurred, which is a rare complication.

PMID- 11505701
TI  - [Acute kidney failure and ascites in Burkitt's lymphoma of the stomach].
AB  - A case of 25 old man with acute renal failure as the result of uric acid
      nephropathy in Burkitt's lymphoma of the stomach and ascites, probably chylous,
      is presented. After starting chemotherapy a regression of stomach tumor and the
      chylous effusion was observed. Unfortunately, after a short period of remission
      the regression was observed with tumor lysis syndrome. The reason of death was
      bleeding from digesting tract.

PMID- 11505702
TI  - [Internal medicine on the turn of the 20th and 21th century].

PMID- 11505703
TI  - [Osteoporosis as the long-term adverse effect of tumor treatment].

PMID- 11505704
TI  - [Risk factors of coronary heart disease in women].

PMID- 11505705
TI  - [Current clinical application of bacteriophages and perspectives for their
      genetic modifications].

PMID- 11505706
TI  - [18th Congress of the Polish Rheumatological Society, Wroclaw, June 15-18, 2000].

PMID- 11505707
TI  - Breast reconstruction using free tram flap transfer--ten years experience.
AB  - Over the course of ten years, 119 breast reconstruction procedures using a free
      TRAM flap transfer were performed in our department. In the present review, the
      authors explain the indication pattern for breast reconstruction. The age of
      patients undergoing breast reconstruction is given, as well as a description of
      the time interval between mastectomy and breast reconstruction, which recipient
      vessels were used, the general and local complications and the complications
      relating to the anastomosis. The review of the group of patients is supplemented
      by information on the time interval between breast reconstruction and
      reconstruction of the nipple areolar complex as well as summarized data on the
      results of breast reconstruction that were achieved using a free TRAM flap
      transfer.

PMID- 11505708
TI  - Aplasia of the breast--reconstruction using a free tram flap.
AB  - Breast aplasia and hypoplasia are found most frequently in Poland's syndrome but
      may also be the consequence of damage to the germ of the mammary gland in
      childhood. The authors present two cases of breast aplasia in which
      reconstruction was implemented by free transfer of a TRAM flap. The internal
      mammary vessels were used as recipient vessels, the condition of which was tested
      before surgery by Doppler. In both instances the reconstruction was implemented
      at the age of 19 years, and subsequently the areolomammillary complex was created
      and the contralateral breast corrected to achieve symmetry. The use of autologous
      tissue in the form of a free TRAM flap provides, in this indication, very good
      results that are permanent, and the problems associated with the use of implants
      are eliminated.

PMID- 11505709
TI  - Breast reconstruction as an integral part of breast carcinoma therapy (a self
      present final report of a research project IGA MZ CR).
AB  - This comparative prospective study elucidates whether breast reconstruction that
      is not associated with systemic oncological treatment may trigger a tumour
      relapse, and if there is any difference between the evaluated reconstruction
      methods, a simple procedure using an implant versus a TRAM flap, on this
      hypothetical influence. The study group of 95 patients suffered from stage I-II
      of breast carcinoma. As regards the available reconstruction procedures, the
      study group was divided into two subgroups, the first using an implant (n1 = 33)
      and the second using a TRAM flap (n2 = 62). All oncological problems manifesting
      during the subsequent 12 months were considered as a response to the
      reconstruction. The oncological course was compared with two control groups. The
      first control group (k1 = 82) corresponded to the study group in terms of tumour
      stage (I-II), average age, time of initial diagnosis, type of primary surgery,
      i.e. mastectomy with axilla exenteration, and subsequent oncological treatment.
      The second control group (k2 = 19,625) was based on the National Oncology
      Register data. It was formed from all patients with breast carcinoma stage I-II
      from 1985-1994. The disease development in terms of the relative number of
      relapses and deaths was compared to the number of healthy and living patients,
      respectively, in the preceding year. The working hypothesis of late breast
      reconstruction (i.e. not associated with oncological treatment) being a possible
      trigger effect on the subsequent course of breast cancer has not been confirmed.
      No statistically significant differences at the 5% significance level were found
      between individual reconstruction methods and control groups in terms of the
      number of local relapses and survival length.

PMID- 11505710
TI  - Local treatment of facial lipodystrophy in patients receiving HIV protease
      inhibitor therapy.
AB  - Localized facial lipodystrophy is a socially disabling complication affecting
      many HIV-seropositive patients receiving triple combination therapy. The exact
      pathogenesis is not well understood and proper therapy is not available. The
      purpose of this pilot-study was to determine whether a hyaluronic acid get, used
      to treat wrinkles for cosmetic reasons, would be a safe and effective treatment
      for facial lipodystrophy in patients receiving triple combination therapy. Seven
      patients were treated with intradermal gel injections after skin tests. There
      were no immediate or late allergenic reactions or other side effects. Within the
      limitations of the product, overall satisfaction regarding the results was high.

PMID- 11505711
TI  - Special features of burn injuries in elderly patients.
AB  - Types of burns and other aspects of burn injuries and case outcomes were assessed
      in a group of geriatric patients (> 60 years) and a younger group of patients (40
      59 years). Between 1990 and 1999, 137 geriatric patients (47 [34%] males and 90
      [66%] females) were admitted to the Burn Centre and Reconstructive Surgery Centre
      at University Hospital in Brno. We compared findings in this elderly group to
      those in 176 younger burn patients (126 [72%] males and 50 [28%] females) who
      were treated at the centre during the same time period. Age and concomitant
      chronic disease contribute to the high mortality and a higher frequency of
      complications in geriatric patients who suffer burn injuries. In this study, the
      complication rates for geriatrics during hospitalization (44% in males and 32% in
      females) and the elderly patients' mortality rates (26% in males and 17% in
      females) differed statistically from the corresponding rates in the younger
      patient group. It is important to know the special needs of elderly burn patients
      because this patient group is expected to grow in parallel with the rising
      average age of the Czech Republic's population.

PMID- 11505712
TI  - Quality of life in burn victims: a holistic approach.
AB  - The prognosis of burn patients is dependent--apart from adequate treatment--upon
      health care system and health care professionals, regarding not only survival,
      but also life-long quality of life. The protection of patients' rights is spelled
      out in the European Countries' constitutions, charters or basic laws. The Code of
      Patients' Rights in the Czech Republic in 1992 entitles the patients to
      respectful and professional treatment, to be able to make decisions, ev. to
      refuse treatment, to the presence of their own families, to continuity of
      treatment after discharge, to withhold consent to students' participation in the
      curative process, to die with dignity. The increasing interest in economic
      justification of any treatment in the EU calls for considering the ethical
      aspects. There has been differentiated intuitive ethics, ethics based on
      principles of Hippocrates, ethics defined by duties, ethics defined by
      consequences, influencing the quality of life (Grant, 1998). The age of patients
      should not play any role in decision--making concerning diagnostic or curative
      procedures. However, in geriatric burn patients the "aggressive" therapy should
      not deteriorate their last days. From the ethical point of view there should be
      applied "palliative care". The age is a significant factor in the permanent
      sequels in children and youngsters, in whom scar deformities cause the loss of
      "body image" and severe psychological problems when the Patients Rights
      (comprehended in the Code of Czech Republic) are not respected.

PMID- 11505713
TI  - [Percutaneous transluminal septal myocardial ablation in the treatment of
      hypertrophic obstructive cardiomyopathy: short-term study].
AB  - In 18 patients with symptomatic hypertrophic obstructive cardiomyopathy 18
      procedures involving percutaneous transluminal myocardial ablation were
      performed. The patients were followed up for three months after the procedure.
      The mean intraventricular peak gradient declined during the intervention from 51
      +/- 26 mm Hg to 11 +/- 12.2 mm Hg (p < 0.001). On average 2.7 +/- 1.1 ml ethanol
      were administered, as a rule into the first septal branch. The target artery was
      detected in 13 instances by means of myocardial contrast echocardiography and in
      five instances by haemodynamic investigation. In one instance the procedure was
      combined with subsequent balloon angioplasty of the ramus circumflexus. In one
      patient it was necessary to implant ex post a permanent pacemaker on account of
      AV bloc grade III. In one instance when myocardial contrast echocardiography was
      not used) infarsation not only of the basal interventricular septum occurred but
      also of the posterolateral left ventricular wall. During the three-month follow
      up the incidence of stenocardias assessed according to CCS declined from grade
      2.6 +/- 0.8 to 0.8 +/- 0.8 (p < 0.0001). Dyspnoea evaluated according to NYHA
      declined from grade 2.9 +/- 0.5 to 1.4 +/- 0.6 (p < 0.0001). The maximal
      intraventricular gradient evaluated by Doppler echocardiography declined from
      57.2 +/- 42 mm Hg before the procedure to 19.7 +/- 12 mm Hg (p < 0.001). An
      identical gradient after stimulation with one dose of isosorbide dinitrate spray
      (1.25 mg) declined from 82.3 +/- 27 mm Hg to 25 +/- 6 mm Hg (p < 0.0001). The
      diastolic thickness of the IVS in the intervened segment declined from 21.2 +/- 3
      mm to 14.7 +/- 2 mm (p < 0.0001). No significant change in the size of the left
      ventricle was recorded, nor in its ejection fraction and size of the left atrium.
      One patient died suddenly during the follow up period. Percutaneous transluminal
      septal myocardial ablation leads during short-term follow-up to a significant
      weakening of the basal segment of the interventricular septum, a decline of the
      intraventricular gradient and symptomatology of hypertrophic obstructive
      cardiomyopathy.

PMID- 11505714
TI  - [Complications in administration of contrast media in the catheterization
      laboratory: a 5-year retrospective study].
AB  - Iodine contrast substances (CS) are used since the twenties of the 20th century.
      From the chemical aspect benzoic acid derivatives are involved which are
      classified according to their osmolality (high-low- and isoosmolar) tendency of
      ionization (ionic and non-ionic) and according to the molecular structure
      monomers and dimers). Side-effects are due to their osmotic, ionic and chemical
      action on tissues. They include a number of systemic and organ symptoms
      (cardiovascular, immunological, haemocoagulation, neurological and renal), from
      the clinical aspect divided into mild, medium severe and severe. The relatively
      high incidence of undesirable reactions when ionic high-molecular CS are used led
      to the-development of non-ionic preparations with a lower osmolality, the more
      extensive use of which is limited by economic factors. Moreover so far convincing
      clinical data are lacking that the higher incidence of undesirable reactions
      after the use of CS has a clinical impact. OBJECTIVE: To summarize experience
      with administration of CS in the catheterization laboratory of the Cardiocentre
      of the General Faculty Hospital during diagnostic and intervention procedures
      within 5 years with regard to the occurrence of undesirable effects when
      comparing ionic and non-ionic CS. METHOD: Retrospective analysis of a group of
      patients examined in the catheterization laboratory to whom a CS was administered
      during the period between Jan. 1 1995 and Dec. 31 1999. RESULTS: In 1995-1999 (5
      years) in the catheterization laboratory a total of 10,149 procedures where
      implemented where ionic (ioxitalam-Telebrix 350) and non-ionic (iopromide
      Ultravist 370, ioversol--Optiray 370 and iomeprol-Iomeron 350) contrast
      substances were administered. Ionic CS were administered in 4,668 (46%) and non
      ionic CS in 5,481 (54%) instances. Undesirable effects were recorded in a total
      of 107 (1.1%) patients, incl. ventricular fibrillation in 76 (0.75%), cardiac
      arrest in 12 (0.12%) and in 19 (0.19%) there were other undesirable effects
      (weakness, nausea, hypotension, flush, urtica etc.). Ionic and non-ionic CS
      participated equally in complications: ionic CS in 53 (49.5%) cases and non-ionic
      CS in 54 (50.5%), whereby no difference was observed in the type of
      complications. No death in conjucntion with administration of CS was observed.
      CONCLUSION: The use of contemporary contrast substances in the catheterization
      laboratory for diagnostic and intervention procedures on the heart is relatively
      safe with a minimal risk of development of serious complications. No difference
      was observed between the use of ionic and non-ionic CS.

PMID- 11505715
TI  - [Pathologic gastroesophageal reflux in patients with bronchial asthma].
AB  - Gastrooesophageal reflux (GER) and asthma bronchiale are frequent diseases.
      Asthma affects some 3-10% of adults. Gastrooesophageal reflux is present in some
      45-89% asthmatic patients. Symptoms of GER are not only gastrooesophageal, and
      recently increased attention is focused on extraoesophageal symptoms where in
      particular the relationship of GER and asthma or chronic cough is investigated.
      At our clinic we implemented a pilot study with the objective to monitor the
      presence of pathological GER in patients with asthma and to assess whether
      antireflux therapy will influence the respiratory complaints of the patients. The
      group was formed by 14 patients selected at random with different severity of
      asthma and different symptoms of GER. The patients had a baseline examination
      evaluating the presence of GER (24-hour pH metry) and pulmonary function (FEV1).
      In case of a pathological GER the patients were treated by antireflux therapy and
      then check-up examinations were made. It was found that after treatment of GER in
      patients with asthma in particular subjective symptoms improved such as cough and
      pyrosis which leads to a substantial improvement of the quality of life. On the
      other hand reflux treatment did not exert a basic effect on pulmonary functions
      and it was not possible to reduce the medication of asthma.

PMID- 11505717
TI  - [Thromboembolic complications in the use of oral estrogen-gestagen
      contraceptives].
AB  - Deep vein thrombosis is a serious complication of oral contraception. The most
      serious complication, pulmonary embolism, could be lethal. The relative risk of
      thromboembolic disease is four time higher in women using oral contraception.
      Both the amount of estrogen and the type of gestagen can increase the relative
      risk of thromboembolic disease. Oral contraceptives influence procoagulants,
      fibrinolytic system and inhibitors of coagulation. The choice of oral
      contraceptive should be very careful. It is advised to use preparations with less
      then 50 micrograms of ethinyl-estradiol and the type of gestagen that has minimal
      metabolic side effects, including minimal effect on coagulation. It is not
      recommended to perform screening of trombophilia before prescribing oral
      contraception. Family history of thrombosis is indication for more detailed
      investigation. However in the case of positive history of thromboembolic disease
      use of oral contraception is contraindicated. Oral contraception users should be
      informed about increased risk of deep vein trombosis, and what to do to prevent
      deep vein thrombosis.

PMID- 11505716
TI  - [Changes in the risk profile and the development of hypertension in the
      population of Plzen 1987-1989 and 1995-1996].
AB  - OBJECTIVE: To evaluate risk factors and the general risk profile in a
      longitudinally followed-up cohort of the Plzen population. MATERIAL AND METHODS:
      The investigation was made in a cohort of 332 men and 280 women selected from the
      epidemiological study PILS II (Plzen longitudinal study) examined in 1987-1989
      and 1995-1995. Both investigations adhered to the standard protocol. Anamnestic
      data were assessed, anthropometric parameters (BMI). Blood pressure (BP) was
      assessed by means of a mercury sphygmomanometer using the standard procedure,
      biochemical parameters were examined from a blood sample on fasting in the
      routine laboratories of the Faculty Hospital Plzen. Changes of individual factors
      were evaluated by the paired Wilcoxon test and chi 2 group test resp. The global
      coronary risk was calculated by means of logistic coefficients from the
      Framingham study. RESULTS: In the cohort which aged on average by 7.6 years the
      number of smokers decreased in men by 8.1% and by 3.6% in women. The blood
      pressure increased significantly in both sexes, there was an increase in the
      number of hypertensive subjects by 26.8% in men and 21.7% in women. In men there
      was a significant decrease of non-HDL cholesterol, in women, there was a
      significant increase of subjects with diabetic dyslipidaemia. The total coronary
      risk (Framingham score) increased after standard transposition to the age of 60
      years only by 0.5% in men and women, which reflects the risk due to increased BP.
      The standard of treatment of hypertension was quite unsatisfactory. When using
      criteria SBP > or = 140 and/or DBP > or = 90 mm Hg during the second examination
      71% of the patients remained without treatment. The number of subjects not aware
      of hypertension declined from 54% to 19.3% of subjects. A favourable indicator
      was the finding that there was a decline of hypertensive subjects with a high
      coronary risk (> or = 20% from ca 11 to 6%). CONCLUSION: During the investigation
      period in the cohort which to a certain extent represents the Plzen population a
      certain improvement of the risk profile occurred in particular as regards smoking
      and disorders of the lipid spectrum, however not as regards the prevalence and
      treatment of hypertension. Despite the favourable development in the Czech
      population in the investigated cohort, obviously at the expense of poor control
      of hypertension, the average coronary risk did not improve.

PMID- 11505718
TI  - [Diabetes mellitus in the elderly].
AB  - Diabetes mellitus is one of the most frequent chronic diseases of the elderly
      population with a high prevalence after the age of 65 years. In this group it is
      a serious cause of increased mortality and morbidity. More than 90% of patients
      suffer from type 2 diabetes mellitus. The disease takes frequently for a long
      time an asymptomatic course and if it persists for long it may lead to
      microvascular complications and is an important risk factor of cardiovascular and
      cerebrovascular diseases. The objective of treatment of diabetes in old age is in
      particular to restrict symptomatic hyperglycaemia, but at the same time we must
      not forget prevention of hypoglycaemia. It is also important to diagnose and
      treat diabetic complications. As elderly diabetic patients are usually
      polymorbid, diabetes mellitus in old age calls for a comprehensive approach not
      only to the treatment of hyperglycaemia but also of hypertension, dyslipidaemia
      and other associated diseases.

PMID- 11505719
TI  - [Concomitant radiochemotherapy in solid tumors].
AB  - The need for improved cancer control led to the investigation of combined
      modality therapy for many cancers. This review is an attempt of analysis of
      possibilities to apply simultaneously both treatment modalities in treatment of
      cancer diseases and shows the possible mechanism of interaction between
      chemotherapy and radiotherapy. Further in this review is showed benefits of this
      method combined therapy and strategies of using chemotherapy and radiotherapy to
      treat different cancers.

PMID- 11505720
TI  - [Leptin--a new acute phase reactant].
AB  - Leptin, 16 kDa protein and the product of the Ob gene was discovered six years
      ago and characterized as a fat cell hormone which maintains via specific
      receptors in the hypothalamus by a feedback mechanism the energy balance and body
      weight. Research conducted during the last three years detected further
      properties of this protein which include it, in addition to its basic role in
      mammalian metabolism, also among acute phase reactants. Leptin is as to its
      structure, pattern of the receptor and the postreceptor transduction mechanism
      close to the group of cytokines of interleukin 6, in particular the granulocytic
      colony stimulating factor. During infectious and non-infectious inflammatory
      reactions leptin synthesis is stimulated by a combination of inflammation
      promoting cytokines. The mechanism of induction is not known so far but the
      majority of investigations proves an indirect stimulating effect of the tumour
      necrosis factor and interleukin 1, depending on non-specified cytokines of the
      second stage. Investigations of cell lines and animal experiments provided
      evidence of some local and systemic effects of leptin which may play a
      physiological part in the acute phase reaction. Leptin mediates at least partly
      the anorectic effect of the tumour necrosis factor and interleukin 1 during
      inflammation. Synergically with bacterial antigens it activates macrophages,
      enhances their phagocytic capacity and stimulates secretion of pro- and anti
      inflammatory factors from macrophages. Leptin stimulates neovascularization, it
      has a stimulating effect on precursors of white blood cells and potentiates the
      effect of erythropoietin on red blood cells. It is obviously an essential factor
      for T-lymphocyte proliferation and development. The authors discuss also the role
      of leptin in the modulation of the hypothalamo-pituito-adrenal stress axis.
      Leptin is a factor of the inflammatory mediator network, probably essential for
      an adequate course of the inflammatory defence reaction.

PMID- 11505721
TI  - [Central salt-wasting diuresis syndrome as a cause of hyponatremia in patients at
      the internal medicine department].
AB  - Hyponatremia is a common electrolyte disorder related to central nervous system
      diseases and is often attributed to the syndrome of inappropriate antidiuretic
      hormone secretion (SIADH) and on the other hand to the cerebral salt wasting
      syndrome (CSWS). This syndrome is characterized by hyponatremia due to excessive
      renal sodium excretion resulting from a centrally mediated process. Given the
      divergent nature of the treatment it is of paramount importance for a clinician
      to be able to recognize and differentiate between these two entities. Thus the
      monitoring of renal function tests, which are needed for earlier diagnosis of
      effective osmolality disorders, is important to do in intensive care units, which
      are caring for patients with central nervous system lesons. Two patients
      successfully treated for CSW due to ischemic stroke caused by arterial embolism
      from heart cavities are described.

PMID- 11505722
TI  - [Systemic disease caused by the fungus Aspergillus fumigatus in immunocompromised
      patients].
AB  - The authors describe an invasive pulmonary Aspergillus infection in three
      immunocompromised patients (1x plasmacytoma, 1x autoimmune thrombocytopenia, 1x
      asthma bronchiale) and draw attention to the possible occurrence of this disease
      also in subjects without serious neutropenia. The common risk factor in all three
      patients was corticoid treatment. In immunocompromised patients only early
      adequate and sufficiently long antimycotic treatment gives hope that the
      infection will be controlled.

PMID- 11505723
TI  - [Sideropenic anemia as a manifestation of selective iron malabsorption].
AB  - The objective of the paper is to draw attention to the not very frequent and thus
      omitted form of sideropenic anaemia in selective iron malabsorption as the only
      manifestation of malabsorption syndrome in coeliac sprue. This type should be
      suspected when examination of blood losses is futile and oral iron administration
      which is usually administered empirically produces no effect. The authors present
      the example of two patients with severe sideropenic anaemia where the diagnosis
      of malabsorption was confirmed only several years after the diagnosis of
      sideropenic anaemia was established. Evidence of a correct conclusion was
      permanent normalization of haemoglobin values when the patients adhered to a
      gluten-free diet.

PMID- 11505724
TI  - [Discovery of blood cells in the 17th century].
AB  - Landmark works of the 17th century concerning observations of blood cells are
      quoted in the article. "Simple" and successively "compound" microscopes made
      their appearance in the late 16th century and early 17th century. In 1656,
      Frenchman Pierre Borel, physician-in-ordinary to the King Louis XIV, who first
      applied the microscope to medicine described a type of "worn" found in human
      blood. In 1657, Athanasius Kircher, a Jesuit priest and scientist from Germany,
      examined blood from plague victims, and described "worms" of plague. In 1661,
      1664 and 1665, the blood cells were discerned by Marcello Malpighi. In 1678, the
      red blood corpuscles was described by Jan Swammerdam of Amsterdam, a Dutch
      naturalist and physician. The first complete account of the red cells was made by
      Anthony van Leeuwenhoek of Delft in the last quarter of the 17th century.

PMID- 11505726
TI  - [Health pedagogy instead of consolation. Theological adjustment to illness by
      Philipp Melanchthon and Caspar Peucer].
AB  - Subject of this paper is the interpretation of disease as physical evil (malum
      physicum) by the university professors Philipp Melanchthon (1497-1560) and Caspar
      Peucer (1525-1602) at Protestant Wittenberg. Melanchthon and Peucer settled the
      problem of theodicy principally by theological strategies of moralization and
      compensation. In most cases, therefore, disease resulted from inadequate health
      behavior, especially drunkenness, furthermore from disdain for medicine and
      obstruction of divine healing. As a rule, natural factors (e.g. celestial bodies
      or human affections) only contributed to disease. In general it was caused by
      free will. In consequence the strategies of depotentiation and functionalization
      of disease became insignificant resulting in the accentuation of its evil nature.
      By way of compensation Melanchthon and Peucer stressed the Divine healing of
      disease. God created the natural remedies and later He created the medical arts
      by granting heroic virtue to the greatest doctors (Hippocrates, Galen, Avicenna).
      Moreover the divine Trinity could directly harmonize affections. Thus, God
      incited a psychosomatical healing within the human organism. As far as physical
      evil is concerned Lutheran pathology substituted medieval pessimism for
      therapeutical optimism. Melanchthon and Peucer strived to discipline the
      patients' behavior and to legitimate the medical arts by God. In this sense their
      pathology formed part of a program of social and religious stabilization. The
      academic medicine profited greatly from that program in later years.

PMID- 11505727
TI  - [Historical development of grading of malignant soft tissue tumors].
AB  - This article describes the historical development of the grading systems for
      malignant soft tissue tumors. First attempts to grade these tumors were made in
      the middle of the nineteenth century; a remarkable amount of activity in grading
      took place in the 1970s with an apex in the 1980s. Reviewing the literature back
      to the first available publications, five phases in the development of the
      grading systems for malignant soft tissue tumors could be distinguished: 1845
      1919: phase of identification, 1927-1964: phase of description, 1965-1977: phase
      of predominant mitotic activity, 1979-1983: phase of predominant tumor type, from
      1984: phase of multifactorial systems.

PMID- 11505729
TI  - [A zoologist on a different path--Richard B. Goldschmidt (1878-1958) as sexuality
      researcher and his reception by the Third Reich].
AB  - At the beginning of 20th century, genetic research was carried out by many
      different branches of science. Biology, zoology, medicine, psychiatry, and
      psychology took part, so some results were a mixture of the involved sciences and
      not pure genetic. One researcher, who used his experiences from zoology to
      explain sexual orientation in the human race, was Richard B. Goldschmidt (1878
      1958). He published several articles between 1916 and 1927 on this topic before
      he reconsidered his own theses. Greatest feedback he became during the Third
      Reich. Although being Jewish he became professor for life in autumn 1933. When he
      left Berlin for Berkeley in 1936, he began a new scientific career, leaving all
      old theories and ideologies behind. But his "Umwandlungsmannchen"-theory was
      restarted by some German psychiatrists to explain homosexuality. One of these men
      was Theo Lang (1898-1957), who was allowed to publish his articles in the USA and
      in Switzerland. Lang had been one of the founders of the association of Nazi
      doctors and was a member of the SA. Moreover, after 1945 during Denazification he
      was allowed to call for Richard Goldschmidt as witness for his own defence.

PMID- 11505730
TI  - [Discussion of medically supervised family care in Germany. Historical
      development of a policy for social integration of psychiatric patients].
AB  - This article is based on the thesis that family care in the 20th century was
      practiced mainly under pragmatical/economical and therapeutical aspects.
      Depending on time and place, one of the two aspects would dominate while the
      other would serve as supporting motive. The subject of this article is to examine
      selected models of family care in Germany at different times as to their aim
      regarding the social integration of psychiatric patients. The family care
      patients not only lived outside the psychiatric hospitals, but were usually
      employed in household, farming or trade of the foster home. So the integrative
      potential of family care was, and still is, aimed at establishing a living and
      working condition as "normal" as possible. Until 1945, patients who could not or
      were not allowed to return to a completely independent lifestyle, family care
      offered them the widest range of integration and freedom. The often observed long
      lasting stays in families, reflect this rise in quality of life, although many
      were formally still associated with the mental institution. Up to the fifties,
      family care can be evaluated as an attempt of psychiatric hospitals to encounter
      the social isolation of the mentally ill. Nowadays family care is seeing a
      certain renaissance as part of social psychiatry. It is however not always clear
      whether family care can serve as a mean of real integration in the sense of a
      completely independent living and working condition, or whether it leads only to
      an, even if permanent, extramural accommodation of the chronically ill patients.

PMID- 11505731
TI  - Cholera, 2000.

PMID- 11505732
TI  - Copper saturation pathways of the urban population in the Czech Republic.
AB  - The estimation of the copper saturation pathways of the Czech urban population is
      presented. The data on copper concentrations proceed from the System of
      monitoring the environmental impact on population health in the Czech Republic in
      the period 1994-1998. The copper concentrations were monitored in foodstuffs from
      the commercial network, in drinking water at the outlets of the waterworks and in
      the public water main networks, and in the ambient air. The copper levels were
      measured also in biological material to obtain the data on the copper saturation
      of the population under monitoring. The copper intake from foodstuffs and
      drinking water did not vary significantly either in the particular years of
      monitoring or individual cities. The same concerns also the copper levels in
      biological material. The total copper intake for an average adult was estimated
      to be 20.2 micrograms/kg b.w./d., i.e. 1300 micrograms/d. Over 99% of the total
      intake was that from the diet. The exposure from the intake of drinking water as
      well as from ambient air was low. The total daily intake lies in the interval
      1000-2000 micrograms/d which is usually found in the similar studies of the
      copper intake. It represents only 40% of the daily dietary copper intake
      recommended by the JECFA FAO/WHO Commission, 1982. The copper levels in
      biological material did not differ from the reference values, and did not
      indicate any evincible hyposaturation of the population with copper.

PMID- 11505733
TI  - Cohort study on low physical activity level and recurrent acute respiratory
      infections in schoolchildren.
AB  - The purpose of the study was to explain childhood respiratory infections in terms
      of life-style factors like being overweight or physically inactive. In the course
      of the cohort study we gathered data on respiratory health of 1028 preadolescent
      children in Krakow. Recurrent acute respiratory infections (RARI) in children
      have been defined as frequent spells (10 or more infections) over the two-year
      follow-up. In scoring the physical activity level, the data on regularly
      exercising sport and the number of hours spent daily TV watching or doing
      homework have been used. Excessive weight was based on the BMI index. In the
      total sample, the RR estimates of RARI adjusted to BMI and other potential
      confounders were consistently higher in children with low physical exercise (RR =
      2.96; 95% CI: 1.78-4.93) or with moderate exercise (RR = 1.87; 95% CI: 1.33
      2.65). Than among the highly active group. In the subgroups of allergic and non
      allergic or overweight and not-overweight children the adjusted RR estimates were
      consistent with those found in the total sample. We concluded that physical
      exercise in preadolescent children may lessen the risk of acute respiratory
      infections and that the low physical activity is an independent predictor of
      increased risk of RARI besides excessive weight and other potential risk factors.

PMID- 11505734
TI  - Investigation of noise exposure effect on heart rate variability parameters.
AB  - This paper deals with the study of the effect of 135 min exposure to noise with
      intensity Leq 95 dB(A) in experimental conditions. Three experimental sessions:
      before, at the onset, and at the end of the noise exposure were conducted. The
      comparison of heart rate variability (HRV) parameters before and on the onset of
      the experiment showed tendency for significant decrease of the cardiointervals
      variability parameters: standard deviation (SD), sum of positive differences
      between successive cardiointervals (S), total wave energy in the cardiotachogram
      (S*Ns), mean difference between successive cardiointervals (V). Statistically
      significant increase of the mean value was found at HRV parameters related to the
      distribution of the cardiointervals: control adequacy parameter (IARP),
      equilibrium autonomic parameter (IVE), autonomous balance (IVB), homeostasis
      parameter (HI). At the end of the third experimental session HRV parameters were
      almost restored, but they did not achieve the initial values. An elevation of the
      sympathetic activity under noise exposure effect was found. In this aspect, the
      heart rate variability parameters were interpreted as a sensitive indicator for
      the quality of cardiac rhythm and they can be used for assessment of the
      functional status and the level of preserving of the adaptive reserves of the
      investigated persons.

PMID- 11505735
TI  - Comparison of the indoor air quality in mould damaged and reference buildings in
      a subarctic climate.
AB  - The purpose of this study was to search for objective parameters most relevant to
      indicate microbial problems of buildings in cold climate. Various indoor
      characteristics were compared in nine buildings with known history of moisture
      problems and visible mould (index) and in nine matched reference buildings. The
      concentrations of airborne viable fungal had a clear difference between the two
      groups of buildings. In this study, airborne concentrations of viable bacteria,
      formaldehyde, total volatile organic compounds (TVOC) and the occurrence of house
      dust mites in these index buildings were compared with the levels of the
      pollutants in matched reference buildings. Fungal growth and flora on moist
      building materials were also studied. The concentrations of TVOC were slightly
      higher in the index buildings than in the reference buildings. However, the
      differences in the concentrations or appearance of any of the studied pollutants
      were not significant. These parameters do not seem to be relevant indicators of
      microbial growth or surrogates of microbial exposure. Thus, fungal concentration
      and composition of fungal genera in the air still seems to be the best indicator
      for moisture problems among the studied pollutants. In the moist building
      materials, some fungal genera, such as Ulocladium and Chaetophoma were detected
      that were not found in indoor air showing that building material samples give
      additional information on the microflora of the building.

PMID- 11505736
TI  - The chemical composition of African haze.
AB  - The LAMMA technique (Laser Microprobe Mass Analyzer) is a valuable and powerful
      technique for the analysis and characterization of particulate air pollutants. At
      seven sites in Zimbabwe, Africa, dust particles were collected and 200 single
      particles were analyzed for each sampling point. The main chemical species
      present in the particles are Na+, K+, Cl, NO3+ and SO4(2-). Beside these, soot
      particles, containing carcinogenic polynuclear aromatic hydrocarbons were found.
      Biomass burning was identified as the major source of the dust particles what is
      in accordance with the assumed air quality for our sampling period.

PMID- 11505737
TI  - Proposed standard definition for child overweight and obesity.
AB  - The prevalence of obesity in child population is becoming a serious problem in
      all advanced countries. Therefore many authors try to find a definition according
      to which it would be possible to assess overweight and obesity in examined
      subjects in a simple manner. The simplest way is to plot the subject's data in a
      percentile zone of reference data according to his BMI value. The problem is
      dealt with e.g. by Cole et al. (1) who defined internationally acceptable
      standards of BMI for children and adolescents from 0-18 years. These standards
      are, however, based only on six national studies and on the assumption that in
      the population of 18-year-olds there are 10% subjects with BMI values above 25
      and 3% subjects with values above 30. The suggested standards thus raise the
      level of the 90th and 97th percentile, as compared with BMI reference data of
      1991 which are used in the Czech Republic. Therefore the ratio of obese children
      in the Czech Republic and in many other countries would be very small.
      Internationally acceptable standards should be therefore based on a broader
      discussion of the professional public.

PMID- 11505738
TI  - Smoking and some life-style changes in medical students--Slovakia, 1995-1999.
AB  - INTRODUCTION: The main goal of a questionnaire cross-sectional study was to
      compare the changes of smoking habits in medical students between 1995 and 1999.
      Beside this, other factors of life-style such as alcohol consumption, nutritional
      status [studied through body mass index (BMI)] and citrus consumption were
      studied. METHODS: Cross-sectional questionnaire study in 453 medical students of
      1st to 5th academic years of the Jessenius Faculty of Medicine, Comenius
      University in Martin, Slovakia, carried out in October and November 1999. Data on
      smoking habit were compared with a similar study carried out in 1995. RESULTS:
      Prevalence of regular smoking (min. 1 cig/day) was 13.6% in men and 8.9% in women
      and did not change significantly in comparison with 1995. In women, prevalence of
      occasional smokers increased from 7.3% in 1995 to 19.8% in 1999 and almost
      reached men in the same year (21.8%). During this period significantly decreased
      proportion of respondents who have never smoked both in men (from 43.0 to 23.3%)
      and women (from 61.9% to 18.2%). Excessive drinking dominates in men, overweight
      (BMI > or = 25) had 16.0% of males and 2.0% of females and excessive underweight
      (BMI < or = 17.5) 1.0% of men and 2.8% of women. More than one half of
      respondents consumed less than 1 piece of citrus fruit per day. CONCLUSIONS:
      Smoking of men still predominates, however, the most apparent changes of smoking
      habit in regard to increasing proportion of smoking women, particularly
      occasional smokers. This indicates increasing social tolerance of smoking. In
      female a possibility of eating disorders deserve attention and a need for the
      improvement of diet is felt in both sexes.

PMID- 11505739
TI  - Study of lung cancer and residential radon in the Czech Republic.
AB  - Epidemiological evidence of lung cancer risk from radon is based mainly on
      studies of men employed underground in mines where exposures are relatively high
      in comparison to indoor exposure. Risk from residential radon can be estimated
      from occupational studies. Nevertheless, as such extrapolations depend on a
      number of assumptions, direct estimation of the risk is needed. The present study
      of lung cancer mortality was designed as a follow-up of a population (N = 12,004)
      in a radon prone area of the Czech Republic covering the period 1960-1999.
      Information on vital status and causes of death were obtained mostly from local
      authorities and from the national population registry. Exposure estimates were
      based on one year measurements of radon progeny in most houses of the study area
      (74%). Exposures outside the area (16%) were based on country radon mapping. Mean
      concentration of 509 Bq/m3 is higher than the country estimate by a factor of 5.
      By 1999, a total of 210 lung cancers were observed, somewhat more than the
      nationally expected number (O/E = 1.10) in comparison to generally low numbers
      corresponding to cancers other than lung (O/E = 0.81). The excess relative risk
      per standard radon concentration (100 Bq/m3) was 0.087 (90% CI: 0.017-0.208).
      This value is consistent with risk coefficients derived in other indoor studies.
      The present follow-up demonstrated that increased incidence of lung cancer
      depends linearly on exposure in terms of average radon concentration in the
      course of previous 5-34 years. Adjustment for smoking did not substantially
      change this estimate, although the risk coefficient for non-smokers (0.130) was
      higher in comparison to that for ever smokers (0.069), but not statistically
      different.

PMID- 11505740
TI  - Viral water contamination as the cause of aseptic meningitis outbreak in Belarus.
AB  - In the recent years Echovirus-30 associated outbreaks have taken place in
      different European countries. Aseptic meningitis caused by Echovirus-30 was the
      main diagnosis of a large outbreak in Belarus in Summer-Autumn, 1997, involving
      460 patients. Echovirus-30 was detected in cerebrospinal fluid of the patients
      with aseptic meningitis. This serotype played the dominant role in the outbreak.
      Minor serotypes and mixtures of enteroviruses were detected in faeces and
      nasopharyngeal lavages. Investigation of environmental samples gave evidence of
      expressed viral contamination of drinking water and water sources (river and
      ground sources). River water sources were considerably contaminated with viruses.
      The incidence of virus isolation was 50%. After cleaning procedures, the
      incidence became two times lower, proving imperfect water purification and
      disinfection procedures. Sequence analysis of isolates from Belarus (isolates
      from water and patient's cerebrospinal fluid) showed the difference of 0.2%. The
      outbreak peculiarities such as high attack rate and wide-spread of the disease
      incidences, clinical form variability, isolation of outbreak strain from water
      and a good agreement between minor serotypes isolated from faeces and water
      samples as well as correlation in the dynamics of acute intestine infections,
      aseptic meningitis morbidity and bacterial water contamination can be considered
      as evidence of its water-borne. Echovirus-30 isolates from Belarus were very
      closely related to each other and to several European isolates. Sequence
      difference between isolates of 1994-1998 from European countries was found to be
      4.3%. The data can point to the common primary source of enterovirus infection,
      connected to water and to the possibility of epidemic strain transmission from
      neighbouring states to the Republic of Belarus.

PMID- 11505741
TI  - Serological evidence of brucellosis among predisposed patients with pyrexia of
      unknown origin in the north eastern Nigeria.
AB  - Brucellosis is the zoonosis of world wide distribution and common cause of
      economic loss and ill health among animals and human populations. Patients with
      pyrexia of unknown origin (PUO) who were predisposed to brucellosis through
      rearing of animals and consumption of different animal products were tested for
      presence of Brucella abortus antibodies using Rose Bengal and serum agglutination
      antigens. Twenty six (5.2%) of the 500 patients had B. abortus antibody. The high
      titres of 320, 640 and 1280 obtained in the sera of patients in this study are
      suggestive of the endemicity of the disease in this environment. No significant
      difference in age and sex distribution of brucella antibody prevalence was
      observed. Similarly, spatial distribution of brucella antibody in different
      locations was not statistically significant. Although higher serological
      prevalence was noted in children and students than in other populations examined,
      the difference in prevalence between the various occupational groups was not
      significant. Animal handling activities including rearing are not important
      factors in the prevalence of brucellosis. However, among the rearers, the highest
      prevalence (20%) was observed among cattle handlers followed in decreasing order
      of prevalence by goat rearers (10%), mixed sheep and cattle rearers (9%), mixed
      sheep and goat rearers (8%), and 4% among each of sheep rearers and non rearers
      of animals. In addition, consumers of yoghurt and fresh goat milk had higher
      prevalence (20%) than consumers of other milk products. However, brucella
      antibody prevalence between consumers and non-consumers of animal products was
      not significantly different. The high economic loss and public health
      implications of brucellosis necessitates the need for effective surveillance as
      well as appropriate preventive and control measure among human and animal
      populations.

PMID- 11505742
TI  - Microbial contamination of eye drops.
AB  - The microbial contamination of eye drops at the Eye Clinic was studied. In total,
      92 eye drop bottles were examined. 43 bottles were opened and used and 49 were
      unopened and sealed. The contamination rate was found to be 10.2% in unopened
      bottles and 34.8% in opened bottles. The opened bottles had been used for two
      weeks. Six of the samples yielded coagulase-negative Staphylococci and nine
      samples yielded one or two different microorganisms. The contamination rate in
      bottles containing the preservative benzalkonium chloride was 34.4%. Among
      unopened eye drop bottles two samples yielded S. aureus, two coagulase-negative
      Staphylococci and one Bacillus spp.

PMID- 11505743
TI  - [Introduction to molecular genetics of arterial hypertension].

PMID- 11505744
TI  - [The comparison of hypotensive efficiency and tolerability of amlodipine and
      enalapril in patients with essential hypertension].
AB  - In this multicentre, double-blind trial in 176 patients with mild or moderate
      essential hypertension were randomized to amlodipine or enalapril monotherapy
      after 2-week period of placebo. Doses of amlodipine (2.5-10 mg once daily) and
      enalapril (5-20 mg once daily) were titrated to achieve office blood pressure
      below 140/90 mm Hg during 8 weeks of therapy. Both drugs were similarly effective
      in lowering blood pressure and goal blood pressure was achieved in 72.4% patients
      treated with amlodipine and 67.4% with enalapril. Also, degree of reduction of
      blood pressure was similar in both groups. Compared to initial values:
      systolic/diastolic blood pressure decreased by 23.5/14.9 mm Hg in amlodipine
      group and 23.2/14.0 mm Hg in subjects receiving enalapril. However, adverse
      effects, especially dry cough were more frequent in enalapril-treated patients.
      Both amlodipine and enalapril provide significant blood pressure reduction in
      stage I-II hypertension. Tolerance of short-term therapy was good in both groups
      however number of adverse events was significantly lower in amlodipine-treated
      patients.

PMID- 11505745
TI  - [Plasma levels of neuropeptide Y i patients with current myocardial infarction].
AB  - Neuropeptide Y (NPY) has been recently characterised as one of the strongest
      circulating vasoconstrictor peptides, its elevated level may cause coronary
      artery spasm and increase of peripheral vascular resistance. All this contributes
      to ischemic myocardial damage and decrease of regional and global left
      ventricular function. The aim of the study was the examination of NPY plasma
      levels in patients with acute myocardial infarction (AMI) after thrombolytic
      therapy with or without reperfusion. The survey was made in 82 patients with AMI
      after thrombolytic therapy: 40 of them without reperfusion and 42 with
      reperfusion. The control group consisted of 20 healthy persons. Plasma levels of
      NPY were measured before thrombolysis, then 1, 3 and 5 days after, using a
      radioimmunologic method. All patients were treated with aspirin, glyceryl
      trinitrate and thrombolytic therapy (TT) with alteplase (r-TPA). In patients with
      AMI, NPY plasma levels were normal before and 1 day after TT, and were
      significant elevated 3 days after TT 5 days after TT, plasma NPY levels were
      still high in patients without reperfusion, but they decreased in patients with
      reperfusion. There was significant negative correlation between NPY level and
      left ventricular ejection fraction measured 5 days after AMI. During 30-days
      follow up systolic dysfunction of left ventricle with ejection fraction under 40%
      occurred in 21 patients and in 11 of them clinical symptoms of heart failure were
      observed. Using the multivariable regression analysis we showed that NPY
      concentration over 60 pg/ml is the independent factor leading to left ventricle
      systolic dysfunction. The results of our study suggest the contribution of NPY to
      the left ventricular remodeling after AMI.

PMID- 11505746
TI  - [Effects of L-thyroxine suppressive therapy on cardiac mass in patients with
      differentiated thyroid cancer].
AB  - Patients with differentiated thyroid carcinoma (DTC) receive a life time l
      thyroxine therapy in suppressive doses and may exhibit signs of cardiac
      hypertrophy. The aim of the study was to analyze the left ventricle mass
      parameters by echocardiography in patients treated with suppressive doses of
      thyroxine and to relate them to the possible occurrence of cardiac arrhythmias.
      Ninety four patients aged 19-70 years treated chronically with l-thyroxine were
      randomly chosen from the population of patients with DTC without concomitant
      diseases of circulatory system. They were divided into two subgroups according to
      the length of thyroxine therapy (< 60 months and > or = 60 months). Control group
      consisted of 41 healthy volunteers, aged 22-73 years. Heart muscle dimensions
      were measured by echocardiography. Left ventricle mass (LVM) and mass index
      (LVMI) was calculated. Electrocardiography according to Holter was carried out in
      57 patients. The results of echocardiography in the whole group of patients did
      not differ significantly from the control group, although a tendency towards
      higher dimensions of the left ventricle was observed. No correlation of hormonal
      parameters, or thyroxine dose, with LVM or results of Holters ecg was noted. When
      patients were subdivided into two groups, according to the duration of therapy,
      significantly higher values of LVM (215 +/- 64 g versus 186 +/- 55; p < 0.05) and
      LVMI (114 +/- 31 g/m versus 102 +/- 23 g/m; p < 0.05) were observed in patients
      treated > or = 60 months in comparison to the control group. When results of
      Holter's ecg in patients with increased LVMI were analyzed, cardiac rhythm
      disturbances were stated in 50% of them, but most were of minor clinical
      relevance. Suppressive l-thyroxine therapy does not induce significant left heart
      hypertrophy during the first 5 years of treatment. Patients treated through a
      longer period of time should be controlled by echocardiography because of the
      increasing risk of the left ventricle hypertrophy and arrhythmia.

PMID- 11505747
TI  - The systolic function of the left ventricle of the heart in patients with
      hyperthyroidism during therapy.
AB  - Hyperthyroidism is associated with enhanced systolic function. The present study
      was designed to evaluate systolic cardiac function in patients with
      hyperthyroidism during a short-term and a long-term pharmacotherapy. The
      diagnostic value of various indices of the left ventricle function was analysed.
      Fifty-one hyperthyroid patients were investigated before initiation of the
      treatment, after 14 days of therapy with thiamazol (mean dose 54 mg/24 hr), a
      short-term treatment and after attainment of normal thyroid function, a long-term
      treatment (mean period 9 months). Control values were obtained from 30 healthy
      individuals. All investigated subjects were aged 18-50 yr. The following indices
      were determined with ultrasonocardiographic method: preejection period (PEP),
      left ventricle ejection time (LVET), preejection period index (PEPI) and left
      ventricle ejection time index (LVETI), index PEP/LVET, left ventricle shortening
      fraction (LVSF), left ventricle ejection fraction (LVEF), mean velocity of the
      circumferential fiber shortening (mVcf), contractility index (CIx), stroke volume
      (SV), cardiac index (CI), output-pressure index (OPI) and end-systolic wall
      stress (ESWS). Additionally, total peripheral resistance index (TPRI) and double
      product (DP) were calculated. In patients with untreated hyperthyroidism, a
      significant shortening of PEP, PEPI, LVET and low PEP/LVET index and TPRI as well
      as increased LVSF, LVEF, mVcf, CIx, CI, OPI and DP were shown. There was no
      changes in LVETI, SV and ESWS. A short-term treatment resulted in changes in PEP,
      PEPI, LVET, mVcf, CI and OPI in direction of normal values. After a long-term
      treatment all altered indices were normal with an exception of OPI, CI and DP. It
      is concluded that enhanced systolic function of the heart in patients with
      hyperthyroidism becomes normal after pharmacological control of the thyroid
      gland. Some changes are seen after a short-term treatment with thiamazol. The
      indices which reverse early are PEP, PEPI, LVET, mVcf and CI. Changes in ejection
      function of the left ventricle in patients with hyperthyroidism are resulted from
      increased heart rate and were found to be related to total peripheral vascular
      resistance.

PMID- 11505748
TI  - [The assessment of urinary glycosaminoglycans (GAG) excretion during therapy of
      patients with progressive Graves' ophthalmopathy].
AB  - Excessive accumulation of hydrophilic glycosaminoglycans (GAG) in the retrobulbar
      tissue leads to many of the clinical manifestations of Graves' ophthalmopathy
      (GO). We examined the quantitative urinary GAG excretion in 35 patients with GO.
      GAG were isolated from 24-h urine collections by precipitation with
      cetylpyridinum chloride and ethanol according to Bitter. Patients with
      progressive ophthalmopathy showed on the average a twofold increase in urinary
      GAG excretion in comparison to patients with stable ophthalmopathy. The elevated
      values of GAG decreased significantly under treatment and correlated with the
      clinical picture of GO, however no correlation was found between the urinary GAG
      values and actual severity of ophthalmopathy classified according to Werner and
      Donaldson. There was no significant difference in GAG excretion between group 1,
      treated with methylprednisolon and irradiation of retrobulbar tissue and group 2,
      under therapy with methylprednisolon. In conclusion, elevated urinary GAG
      excretion is characteristic for the clinical picture of the progressive GO. The
      remarkable decrease in GAG values during treatment correlated to the positive
      response to immunosuppressive therapy.

PMID- 11505749
TI  - [Statistical analysis of decision making in the treatment in two-vessel coronary
      artery disease].
AB  - The objective of this paper was to analyze the choice of treatment in two-vessel
      coronary artery disease and to evaluate the effectiveness of the chosen
      treatment. The data of sixty-five patients with two-vessel coronary artery
      disease was analyzed. Two-vessel coronary artery disease was recognized when
      critical stenoses were present in two arteries with a diameter no less than 2 mm
      across. Patients who had a CABG were excluded. Patients were divided into three
      groups according to their treatment: those treated with CABG (29 patients), those
      treated with coronary angioplasty (20 patients), and those treated conservatively
      (16 patients). The mean follow-up was 29.3 months (12-48 mo). There were two
      groups of data collected. The first group consisted of data which might have
      influenced the decision-making and state of the patients after they had been
      introduced to the selected treatment. The second group consisted of data
      necessary to evaluate the state of the patients during the follow-up period. The
      statistical analysis was divided into three stages. In the first stage, clinical
      data connected to the selected treatments was studied. In the second, the effects
      of the chosen treatment were examined. During the third stage of analysis,
      variables which influenced the effectiveness of the specific treatment were
      evaluated. Decision-making in patients with two-vessel coronary artery disease
      depended on the co-existence of hypertension, diabetes, lower-limb ischemia and
      earlier-performed coronary angioplasty. The only statistically important
      angiographic feature was the condition of the proximal LAD. Objective
      improvements in the states of patients (evaluated by exercise tests) were
      frequently connected to CABG treatment. Subjective improvements in the states of
      patients were more often connected to conservative treatment. Elevated
      cholesterol levels were connected to the progression of the disease both in those
      treated conservatively and interventionally.

PMID- 11505750
TI  - [Coincidence of multiple myeloma and renal clear cell adenocarcinoma].
AB  - There are only casuistic reports about the coincidence of renal carcinoma and
      lymphoproliferative diseases. We report a case of 59-year old patient who
      simultaneously developed renal clear cell carcinoma and IgG kappa multiple
      myeloma. After nephrectomy the progression of multiple myeloma was observed. The
      renal failure occurred and, as a consequence, the introduction of full doses of
      chemotherapy for multiple myeloma was unable.

PMID- 11505751
TI  - [Pulmonary lymphangioleiomyomatosis as a very rare interstitial lung disease].
AB  - Lymphangioleiomyomatosis (LAM) is a rare lung disease affecting premenopausal
      women characterized by an abnormal proliferation of smooth muscle cells that
      leads to the obstruction of airways, lymph and blood vessels. We present a case
      of a 46-year-old woman who was admitted to our department with dyspnoea and dry
      cough. The patient had a history of spontaneous pneumothorax 2 years prior to
      admission. Physical examination revealed dull percussion note on the lower right
      side of the chest. The chest X-ray film showed diffuse interstitial parenchymal
      infiltration and flattened costodiaphragmatic angle on the right side. The high
      resolution computerized tomography (HRCT) scan showed the numerous air filled
      cysts, about 25 mm in diameter with thin regular walls and liquid in the right
      pleural cavity. The effusion in a pleural cavity was chylous. Airway obstruction
      (FEV1/FVC 57% of predicted), markedly elevated residual volume (140%), and
      decreased DLCO were observed in functional pulmonary tests, and she underwent
      diagnostic videothoracoscopy. Pulmonary biopsy specimens confirmed diagnosis of
      LAM. The patient has been under careful observation, no treatment was instituted.
      The patient remains clinically stabile. During the last six months of observation
      she has normal sex hormone levels, therefore there exists a possibility of
      postmenopausal remission of symptoms.

PMID- 11505752
TI  - [New methods for prevention of thrombosis after coronary stent implantation].

PMID- 11505753
TI  - [Gynecomastia as a symptom revealing tumors other than breast carcinoma].

PMID- 11505754
TI  - [Application of leflunomide in the treatment of patients with rheumatoid
      arthritis].

PMID- 11505755
TI  - [Test your decision-making. When to do endodontic retreatment? Results of a
      study].
AB  - The goals of this survey were to determine the most frequent therapeutic option
      and to evaluate the consensus among a sample of Belgian practitioners managing
      the same simulated cases of root treated teeth. On average, conservative options
      (nonsurgical retreatment 35.27% and no retreatment 29.61%) are the most selected
      alternatives. Surgical options and extraction respectively constitute 21.18% and
      13% of the treatment propositions. As expected, the presence of radiographic
      and/or clinical signs resulted in a more aggressive attitude, but the presence of
      symptoms does not seem to be a valid reason for reintervention. The results of
      the study demonstrate considerable interindividual variations in clinical
      management of root treated teeth, regardless of personal factors, such as gender,
      years of experience and graduation institution. Even if a consensus appears
      within a group of professionals, it is not necessarily applied by a majority of
      practitioners; this contributes certainly to the explanation of the geographical
      or institutional variations noted in the medical practices.

PMID- 11505756
TI  - [Test your decision-making. When to do endodontic retreatment? Some therapeutic
      alternatives].
AB  - The aim of the present article was to propose examples of treatment alternatives
      for the management of 14 clinical cases. All these cases involved endodontically
      treated teeth and have been managed by the same practitioner. In this paper, the
      authors tried to show the variety of treatment alternatives as well as the
      complexity of the decision-making process and, not to consider that proposed
      alternatives were the most adequate.

PMID- 11505757
TI  - [Effects of periodontal disease and its treatment on the condition of the pulp].
AB  - Since there is a close relationship between the periodontium and the pulp, formed
      by the apical foramen, dentinal tubules, lateral and accessory canals, it is
      evident that both compartments influence one other. In this article, the
      influence of periodontal disease and its treatment on the dental pulp is
      described. The review shows that periodontal disease and its treatment, very
      seldom compromise the vital functions of the pulp, but can cause local pulpal
      response. A more common reaction is dentinal hypersensitivity. Although there's
      no clear treatment for dentinal hypersensitivity, this article presents a few
      guidelines for treatment.

PMID- 11505758
TI  - [Direct and indirect effects of medication (including chemotherapy) and
      irradiation on the pulp].
AB  - A direct or indirect effect of the intake of medication on the pulp itself has
      not yet been described in the literature. The effect of local anesthetics on the
      pulp, on the other hand, has been documented. Although local anaesthesia has been
      employed in dentistry for many years, most investigations of its action have only
      considered the effect on the nerves within the pulp using traditional methods.
      Recently it has become clear that the nerves and blood vessels of the pulp do not
      act in isolation but are closely related. In this respect it has been shown that
      there exists a direct relationship between the length of the flow cessation and
      the concentration of vasoconstrictor used. Therefore care should be taken when
      using vasoconstrictors especially where pulpal injury is apt to occur when dental
      procedures such as full crown preparations are performed immediately following a
      ligamental injection. The anaesthetic efficacy of intraosseous injection is well
      documented. The effect, however, on the dental pulpal circulation still remains
      subject of further investigation. Radiotherapy involving the oral cavity and
      salivary glands and chemotherapy (in a lesser degree) induce alterations in the
      oral tissues and the salivary gland functions. Some of these side effects are
      transient. However there are side effects such as the xerostomia which are very
      drastic for the dentition resulting in radiation caries and dental
      hypersensitivity. Tooth anomalies in the developing dentition are also described.
      Due to the rapid progression of the radiation caries a monitoring of the oral
      cavity with strict application of preventive measurements and systematic follow
      up can reduce the incidence of the complications. Unfortunately most of the
      patients belonging to this group consult with the complications of their
      radiotherapy and chemotherapy. In this respect endodontic treatment of the
      severely decayed teeth is an important part of dental treatment. Moreover,
      extraction is regularly contraindicated as osteoradionecrosis is then one of the
      major sequels.

PMID- 11505759
TI  - [The importance of apical and coronal leakage in the success or failure of
      endodontic treatment].
AB  - The present paper reviews the literature and gives the evidence that apical and
      coronal leakage of the root canals may lead to failures of the root-canal
      therapy. It becomes clear that none of the present-day root canal sealers may
      hermetically seal "the root canal wall--gutta-percha filling interface". In this
      respect the importance of perfectly sealing coronal restorations (both temporary
      and permanent) is emphasized.

PMID- 11505760
TI  - [The use of glass ionomer cements in endodontics].
AB  - Glass ionomer cements are currently used in endodontic therapy for sealing root
      canals (orthogradely and retrogradely), for sealing and restoring the pulp
      chamber, for repairing perforations and root resorption defects, and, rarely, for
      treating vertically fractured teeth. The successful use of these cements is the
      result of their particular characteristics: a chemical bond to dentin, which
      enhances the seal of the root canal and the reinforcement of the tooth; a good
      biocompatibility in the periradicular area and a fluoride release without loss of
      strength of the material. The fluoride release imparts an antimicrobial effect to
      combat root canal infection and attributes to bone mineralization after surgery.
      The present paper reviews the literature regarding the various applications of
      glass ionomer cements in present-day endodontics.

PMID- 11505761
TI  - Cultural ecology of Whitethroat (Sylvia communis) habitat management by farmers:
      field-boundary vegetation in lowland England.
AB  - Field-boundary structure, its use by territorial Whitethroats, and its management
      by farmers were investigated in southern Wiltshire using a combination of
      fieldwork and a questionnaire survey. Whitethroats favour wide herbaceous field
      boundary strips and low hedges. Long-term cultural and short-term economic
      interests combine to influence farmers' management decisions. Only farmers with
      game and conservation interests claimed to adopt field-boundary management that
      would benefit Whitethroats, but across all farms, intended and actual herbaceous
      strips were too narrow, and their management too imprecise, for Whitethroats and
      other wildlife. Agricultural advisors and magazines were the main influences on
      farmers' management decisions. Improving habitat for Whitethroats could have both
      agronomic and wider conservation benefits, and the provision of information that
      accommodates farmers' cultural and economic incentives could benefit both farmers
      and wildlife.

PMID- 11505762
TI  - Cultural ecology of Whitethroat (Sylvia communis) habitat management by farmers:
      winter in farmland trees and shrubs in Senegambia.
AB  - The presence of Whitethroats and their potential invertebrate prey in farmland
      trees and shrubs was investigated. The management of this vegetation by farmers,
      and their motivation for that management, was explored using participatory
      techniques. Whitethroats were associated with Guiera senegalensis, the shrub
      species which supports most caterpillars and spiders. Farmers reported declines
      in trees and shrubs since the 1950s, loss of fallow areas, declines in soil
      fertility and crop yields, and increases in the use of fire for clearing fields.
      Trees are valued by people for their cultural and medicinal uses and some species
      used by Whitethroats and other birds have potential for restoring soil fertility,
      although this was not recognised by farmers. More sustainable use of savanna
      farmland could have both agronomic and wider conservation benefits, and the
      provision of information that accommodates farmers' cultural and economic
      incentives could benefit both farmers and wildlife.

PMID- 11505763
TI  - Environmental assessment in countries in transition: evolution in a changing
      context.
AB  - Over the last fifteen years, Environmental Assessment systems of transitional
      societies of Central and Eastern Europe and Central Asia have undergone dramatic
      change from appraisals integrated into centrally planned economies to formal
      procedures aimed to ensure interdisciplinary analysis of environmental impacts
      and linked to publicly accountable decision-making. In most Central European
      nations, EA systems have been radically reformed to approximate the procedures
      used in developed countries, particularly in the European Union. In contrast, EA
      in most of the former Soviet republics has been reformed more gradually and is
      still based on the so-called State Environmental Review procedure inherited from
      the USSR and substantially different from 'Western' EA. About one-third of the
      transitional countries (in the Balkans, the Caucasus and Central Asia) have, so
      far, failed to establish functioning EA systems. Throughout the region, there has
      been a gap between EA legislation and practice, especially concerning
      interdisciplinary analysis of environmental impacts, public participation, and
      utilisation of EA findings in decision-making. A key driving force in the reform
      of EA systems has been the change in their societal context, the so-called
      'process of transition'. Three main policy agendas--environmental protection,
      reforms of decision-making, and conforming to international requirements--along
      with the institutional context of EA regulations and practice have influenced
      both the change of EA systems over time and the regional variations in the
      patterns of their evolution. This study suggests that an effective reform of an
      EA system should be context-sensitive, or be 'in gear' with the political and
      economic transition. Future EA research should consider their changing societal
      contexts and focused on practical effects of applying EA procedures.

PMID- 11505764
TI  - Testing hypotheses about management to enhance habitat for feeding birds in a
      freshwater wetland.
AB  - The level of water was manipulated in a freshwater wetland, with the aim of
      enhancing abundances of benthic animals and, ultimately, improving habitat for
      feeding birds (Japanese Snipe, Gallinago hardwickii). We tested whether these
      actions had the predicted and desired effects on benthic animals, by contrasting
      changes in two managed locations to one control location which was left
      unmanipulated. The number of taxa and abundances of chironomids decreased
      strongly and significantly in the manipulated locations, while the abundance of
      oligochaetes appeared to vary in a seasonal manner. Temporal variability of the
      structure and composition of assemblages was also increased in manipulated
      locations. Such effects have previously been suggested to indicate stress in
      benthic assemblages. Therefore, in contrast to what was predicted, managerial
      actions made benthic fauna less abundant and thus, less suitable as habitat for
      feeding birds. Several general lessons can be learned from these results. (1)
      Effects of managerial actions like these are difficult to predict a priori and
      can only be reliably evaluated with an experimental framework. (2) Because
      abundances of animals vary naturally, evaluations of managerial actions must
      include appropriate spatial replication. (3) Sampling at hierarchical temporal
      scales is important, because abundances of animals may vary in an unpredictable
      manner at short temporal scales and because changes in temporal variability may
      be a symptom of stress. (4) Combined use of uni- and multivariate techniques
      provides a comprehensive set of tools to assess the effects of restoration and
      creation of new habitats. Finally, these results emphasise the need for clear
      predictions about desired outcomes and specific experimental plans about how to
      test whether the desired results were achieved, before managerial actions are
      taken. Although this is often very difficult to achieve in real situations, it is
      necessary for practices of management to evolve on the basis of sound empirical
      experience.

PMID- 11505765
TI  - Turbidity and nitrate transfer in karstic aquifers in rural areas: the Brionne
      Basin case-study.
AB  - The degradation of water quality in many groundwaters of Europe is a major source
      of concern. Rises in turbidity and nitrate concentrations represent present or
      potential threats for the quality of drinking water in rural areas. They are for
      the most part a consequence of agricultural intensification which has
      considerably affected land cover and land use in recent decades. In our case
      study (a karstic catchment) the mechanisms which explain changes in water
      quality, as far as turbidity and nitrate are concerned, result from a strong
      continuity between surface and underground waters. The karstic system of the
      Brionne Basin can be considered as both the focus of rapid horizontal flows
      (runoff, a rapid process in which rainwater reaches the spring directly through
      sinkholes) and slow vertical flows (leaching, in which rainwater filters through
      the soil to the spring). A hierarchical approach to the water pollution problem
      of the basin suggests that turbidity or nitrate concentrations peak during heavy
      rain episodes and are short-term events. In terms of management, this implies
      that the solution to water pollution caused by such events is also short-term and
      can therefore be addressed at a local scale. The rise of nitrate concentrations
      during the past twenty years is the main concern. The solution can only be found
      at a global scale (all the catchment area must be taken in account: land plots
      and their spatial configuration), and by taking a long-term approach.

PMID- 11505766
TI  - Exploratory visualization software for reporting environmental survey results.
AB  - Environmental surveys yield three principal products: maps, a set of data tables,
      and a textual report. The relationships between these three elements, however,
      are often cumbersome to present, making full use of all the information in an
      integrated and systematic sense difficult. The published paper report is only a
      partial solution. Modern developments in computing, particularly in cartography,
      GIS, and hypertext, mean that it is increasingly possible to conceive of an
      easier and more interactive approach to the presentation of such survey results.
      Here, we present such an approach which links map and tabular datasets arising
      from a vegetation survey, allowing users ready access to a complex dataset using
      dynamic mapping techniques. Multimedia datasets equipped with software like this
      provide an exciting means of quick and easy visual data exploration and
      comparison. These techniques are gaining popularity across the sciences as
      scientists and decision-makers are presented with increasing amounts of diverse
      digital data. We believe that the software environment actively encourages users
      to make complex interrogations of the survey information, providing a new vehicle
      for the reader of an environmental survey report.

PMID- 11505767
TI  - The Area Production Model: a tool and concept for sustainable land-use and forest
      resource management.
AB  - In developing countries, planning in the forestry sector has been seen as an
      appropriate instrument to prepare and implement government policies and programs.
      Despite its potential and recent advancements in, for example, remote sensing and
      infrastructure, tropical forest land-use planning is often formal and non
      integrated with agriculture. It rarely involves all legitimate stakeholders and
      neglects taking into account actual land-use. The socio-economic and
      environmental consequences of these shortcomings emphasise the need for
      alternative ways of approaching planning. This article summarises the idea,
      structure and current status of the Area Production Model (APM), originally
      developed in the 1980s, which is now gaining interest as a land-use planning tool
      in Africa and Asia. It describes the development over time of production and
      consumption in agriculture and forestry within a defined geographical area
      operating under different assumptions on management, land use and socio-economic
      and macro-economic changes. From a narrow perspective, the APM is a fairly simple
      computerised tool for generating scenarios. In a broad sense, it is a concept
      comprising the whole planning process including organisation, inventory, data
      analysis, consensus building and strategy. A case-study in Laos, based on
      verified data for a historical period of 45 years, and a review of different APM
      applications in the world over the last 15 years are presented as a base for
      conclusions about its potential and shortcomings. In some cases where the APM
      concept was used in training courses and planning exercises involving
      stakeholders, it generated a strong interest in collecting and analysing relevant
      information. It provides the means of addressing a number of shortcomings in
      current planning.

PMID- 11505768
TI  - A critique of EPA's index of watershed indicators.
AB  - Numerous indices have been developed to assess water quality and the impact of
      programs to improve quality. The Index of Watershed Indicators (IWI) is one such
      index created by the US Environmental Protection Agency to assess watershed
      vulnerability and condition in the United States. The credibility and
      applicability of subjective indices such as IWI depends upon their ability to
      withstand tests that challenge their internal consistency and interpretation.
      This paper critiques IWI on the basis of these tests and other considerations,
      and suggests that explicitly basing the index on multiattribute utility theory
      and methods could help resolve many of these difficulties.

PMID- 11505769
TI  - Stream and riparian management for freshwater turtles.
AB  - The regulation and management of stream ecosystems worldwide have led to
      irreversible loss of wildlife species. Due to recent scrutiny of water policy and
      dam feasibility, there is an urgent need for fundamental research on the biotic
      integrity of streams and riparian zones. Although riverine turtles rely on stream
      and riparian zones to complete their life cycle, are vital producers and
      consumers, and are declining worldwide, they have received relatively little
      attention. I review the literature on the impacts of contemporary stream
      management on freshwater turtles. Specifically, I summarize and discuss 10
      distinct practices that produce five potential biological repercussions. I then
      focus on the often-overlooked use of riparian zones by freshwater turtles,
      calculate a biologically determined riparian width, and offer recommendations for
      ecosystem management. Migration data were summarized on 10 species from eight US
      states and four countries. A riparian zone encompassing the majority of
      freshwater turtle migrations would need to span 150 m from the stream edge.
      Freshwater turtles primarily chose high, open sandy habitats to nest. Nests in
      North America contained eggs and hatchlings during April through September and
      often through the winter. In addition, freshwater turtles utilized diverse
      riparian habitats for feeding, nesting, and overwintering. Additional
      documentation of stream and riparian habitat use by turtles is needed.

PMID- 11505770
TI  - [Physiopathology of repetitive movements and vibrations of the hand-arm system].
AB  - This paper is a review of some recent findings in physiopathology of work related
      upper limb disorders and hand-arm-vibration-syndrome (HAVS). In a first section
      the data relative to work related upper limb musculoskeletal disorders are
      collected in three groups referring respectively to the muscle, to the tendon and
      to the peripheral nerve. Furthermore the physiopathological data are analyzed
      with respect to the Strain Index proposed by Moore and Garg. In a second section
      the physiopathological mechanisms of HAVS are summarized.

PMID- 11505771
TI  - [Diseases caused by repetitive trauma of the upper limbs: epidemiology,
      diagnosis, prevention. Epidemiological aspects].
AB  - The association between occupational risk factors and musculo-skeletal disorders
      due to biomechanical overload (WMSDs) has been focused on numerous research
      projects, ranging from those simple observing the different pathological findings
      reported among workers performing particular tasks, down to the latest studies
      actually quantifying the exposure of workers to basic risk factors, as force,
      awkward posture, repetition and to modifying factors as duration, intensity,
      temporal profile and cold temperatures. The critical review of the
      epidemiological studies, taking into account their quality, showed a clear
      relationship between basic and modifying risk factors and upper limb pathologies.
      In particular, force exertion has been shown strongly related to neck, elbow and
      hand-wrist pathologies; repetition showed some convincing evidence of causal
      relationship to neck, shoulder and hand-wrist pathologies. Insufficient evidence
      of work relatedness has been shown between both repetition and awkward posture
      and elbow pathologies.

PMID- 11505772
TI  - [Medical surveillance and occupational identification of workers exposed to
      repeated movements of the upper limbs].
AB  - Repetitive motions of the upper limb at work can induce muskulo-skeletal
      alterations, therefore a specific medical surveillance is needed, according to
      the intensity of risk. In low risk conditions, the medical surveillance is aimed
      at the identification of hyper-susceptible individuals and the administration of
      specific information programs. When the risk intensity is higher, medical
      surveillance should add the recognition of early symptoms and signs of muskulo
      skeletal disturbances, in order to remove workers showing early alterations from
      the exposure and allow medical rehabilitation. The diagnostic protocols with the
      adequate instrumental evaluation are provided, and the required legal reporting
      is discussed.

PMID- 11505773
TI  - [A pilot study on training and information of workers exposed to biomechanical
      overload of the upper limb].
AB  - Health education (HE) is very important in the prevention of occupational
      diseases, particularly when exposure to risk factors can be reduced through
      working procedures and hygienic behaviours. This pilot study refers to a HE
      program for prevention of work related muscle-skeletal disorders of upper limbs,
      carried out in two groups of 15 and 12 workers, respectively employed in trimming
      and assembling of plastic and metal parts. The first phase of the program
      consisted of worksite inspections and video recording of working procedures,
      characteristics of tools and machinery. This was followed by an informative
      meeting with the workers, which began with the administration of a multiple
      choice questionnaire, designed to evaluate the baseline knowledge about risk
      factors, work related muscle-skeletal disorders of upper limbs, working specific
      procedures and preventive actions. Questionnaires and video recording were
      repeated after two months in the second phase of the program, as subjective and
      objective methods of evaluation of HE effectiveness. In both groups, the
      questionnaire score was significantly increased after the program and a clear
      improvement was shown in the correct working procedures. This HE program
      contributed to increase the level of knowledge of the workers and fostered the
      adoption of working behaviours suitable to reduce the strain for the upper limbs.

PMID- 11505774
TI  - Exposure assessment of upper limb repetitive movements: a consensus document
      developed by the Technical Committee on Musculoskeletal Disorders of
      International Ergonomics Association (IEA) endorsed by International Commission
      on Occupational Health (ICOH).
AB  - This consensus document intends to supply a set of definitions, criteria and
      procedures useful to describe and, wherever possible, to assess the work
      conditions that can represent a physical overload for the upper limbs. The
      document is aimed at all the operators, i.e. occupational doctors but mainly
      technicians, who are, involved in risk exposure assessment and management. The
      document intends to provide methods and procedures easily applicable in the
      field, possibly not requiring sophisticated instrumentation and when possible
      based on observation procedures. The proposed methods shall be based as far as
      possible on knowledge and data from scientific literature: should they be
      contradictory or deficient, reference will be made to standards or pre-standards
      issued by national and international agencies and bodies, with the experience of
      researchers involved and common sense. In this regard, it is to be emphasized
      that the potential users increasingly demand an easily applicable method for
      description and assessment of work with repetitive movements. The group intends
      to give a response even if there are still uncertainties from a strictly
      scientific standpoint: however the group commits itself to perform subsequent
      validations especially of as yet unconsolidated issues. This document focuses
      specifically on identification of risk factors and describes some of the methods
      that have been developed for evaluating them. There is a rapidly developing body
      of literature on job analysis and not yet agreement on a single best way to
      analyze jobs. Professional judgement is required to select the appropriate
      methods. Analysis and design of jobs should to be integrated into an ongoing
      ergonomics program that includes management commitment, training, health
      surveillance, and medical case management. In summing up this report, space must
      be given to the check lists that are so often seen in the medical press, although
      this is not the occasion to propose a detailed analytical review.

PMID- 11505775
TI  - [Active epidemiological surveillance and prevention of diseases caused by
      biomechanical overload of the upper limbs: experience at a territorial service of
      occupational medicine].
AB  - Nowadays in the western countries, the Work Musculoscheletal Disorders (WMSDs)
      are the most relevant work-related diseases either for the large number of at
      risk workers and for the high prevalence of cases among them. Among WMSDs, the
      Carpal Tunnel Syndrome (CTS) is considered a sentinel event in occupational
      medicine and epidemiological surveillance systems were set up to study its
      temporal occurrence and spatial spread. Surprisingly enough, in our country the
      epidemiology of the WMSDs is still unknown; although observations of important
      clusters of cases are increasing, these pathologies are still largely
      underreported by medical doctors. In the high industrialised province of Brescia,
      Northwestern Italy, only 1% of the 25.000 occupational disease, collected by the
      occupational medicine and prevention service of the National Health Service
      (SPSAL) since 1989 to 1997, were coded as WMSDs. Even if the notification of
      these work-related disorders is compulsory by low since 1973, up-to-now very few
      cases were reported to SPSALs, and consequently active prevention programs were
      very few too. For that reason, a project of active surveillance of WMSDs
      diagnosed on the general population was carried out to improve their
      identification and to evaluate the work-related etiological fraction as well as
      to address primary prevention projects. During 1997-1999 618 upper limb
      musculoskeletal disorders were collected from 2 orthopaedic hospital divisions
      where cases underwent surgical treatment. 369 of them were interviewed by
      telephone (253 female, 116 man) and 128 cases (34%) were classified as probable
      professionally exposed to some known hazard. Female were prevalent (71%),
      involved particularly in textile, garments, plastic, food production and domestic
      services. Among men, construction, metallurgic and mechanic were the more
      frequent jobs. 116 WMSDs were reported to the National Insurance Institute
      (INAIL). The collection of these WMSDs was the basis for specific communications
      to the firm manager(s) and to the factory's medical doctor(s) with the aim to
      make it easy: i) a good health surveillance to exposed workers; ii) a specific
      risk assessment; iii) carrying out prevention programs and adopting personal
      protection equipments. Some problems are focused concerning the underreporting of
      cases, the anamnesis information, the fate of interventions to face the problem
      in the workplaces. A possible implementation of this project is also discussed to
      avoid a WMSds surveillance unlinked prevention programs of occupational risks.

PMID- 11505776
TI  - [Diseases caused by repetitive trauma. Trends in accusations and recognitions in
      the field of INAIL].
AB  - In this report the authors describe the situation of the work-related illnesses,
      associated with repetitive manual work (CTD-Cumulative Trauma Disorders-), report
      to the INAIL after the introduction of the mixed system (sentence of
      Constitutional Court 179/88). They described the medical-legal criteriology that
      they follow, disorder report, occupational sectors, the most important regions
      and the connection between the cases arrived to the General Direction and the
      recognized cases in the last five years.

PMID- 11505777
TI  - [Musculoskeletal disorders and the change in work organization].
AB  - In the documentations of the risk assessments required by the Decree 626/94, the
      risk of muscle-skeletal diseases is totally absent. Therefore, the first of our
      worries is to rise this problem and to give it the right social relevance as
      until now it has been considered a pure scientific issue. What is the reason of
      all this? The real reason is that the main source of these diseases is work
      organisation! In the actual work organisation in factories, there are a series of
      correlated risk factors which cannot be corrected without a radical preventive
      action. What is the border-line between physical and pathological strain? The
      acknowledgment of damage is only the starting point. The right way to face the
      decision and to prevent the rise of these diseases is, according to us, a change
      in the work organisation; an ergonomic planning of workplaces; a vision of
      factory manufacturing as the result of a balance among cost factors, health as a
      necessary bound and a progress in the industrial system.

PMID- 11505778
TI  - [Evolution of work duties in manufacturing activities].
AB  - The present work deals with duties' evolution according to the aspect of the
      investment's increase in facilities and equipment for employ, of industry-wide
      agreement, of cost accounting, of added value, of plant lay-out, of job
      competence and of production technologies. The mutual relation between duties and
      risk of cumulative trauma disorders is studied in qualitative and quantitative
      way making use of active and waiting labour time allotment during the labour
      cycle, rest and fatigue factor, labour losses, collective and individual breaks,
      high repeated work and worked items' variability. In conclusion the paper
      presents elements and examples about investments in automation and organisation
      with relay-out.

PMID- 11505779
TI  - [Ergonomic approach to risk control].
AB  - The aim of the paper is to emphasise the role and the importance of the ergonomic
      approach to improve reduction and management of the risk related to repetitive
      strain injuries. The authors tried to select and to put in evidence the risk
      factors related to the investigated problem, proposing a critical analysis of
      them, and to detect some guide lines to design or correct workplaces and tasks.
      These guidelines are based on ergonomic principles and they aim at reducing the
      risk related to repetitive strain injuries. The proposed interventions are
      grouped by a risk-factor criterion.

PMID- 11505781
TI  - [Anatomo-functional aspects and diagnostic algorithm (of the upper limb
      pathologies secondary to repeated trauma)].
AB  - The epidemiology of work-related musculo-skeletal pathologies of the upper limbs
      has become significantly relevant in the last years, and a sharp increasing trend
      can be observed. This paper mainly focuses on the chronic inflammatory and
      degenerative conditions, which are more complex and difficult to accurately
      diagnose and treat. A synthesis of the diagnostic picture of the different types,
      involving the joints, muscles and tendons, and peripheral nerves is provided,
      with mention of the sensitivity and specificity of the main diagnostic tests. The
      possible entrapments of the radial, median and ulnar nerves are described in
      detail. Finally, a brief critical review on the principal movements of the upper
      limbs which are responsible of the onset of such conditions is presented.

PMID- 11505780
TI  - [Musculoskeletal disorders caused by repetitive trauma of the upper limbs: a
      paradigm of the development of occupational diseases and industrial medicine].
AB  - The work related musculoskeletal disorders (WMSDs) are a wide range of
      inflammatory and degenerative disease and disorders that result in pain and
      functional impairment. All available definitions for WMSDS are non consistent and
      require in each individual case and in each group study careful identification of
      symptoms, signs and findings. WMSDs, as a mutifactorial work related disease, are
      associated to physical and psychosocial factors at work and other individual,
      sociocultural factors. They are therefore good paradigm for the changing
      occupational risks and illness and for the new methods that the occupational
      medicine and the preventive disciplines have to set up. The research and
      standardization needs appear to be more evident for framing pathogenesis,
      biological response and pathology of WMSDs and mainly for risk factors
      assessment, since suitable analytical methods are still not available. The
      agreement of valid standardised methods (guide lines) for the evaluation of
      working conditions and assessment of risk factors is required, taking due regard
      to the multidisciplinary approach both in biological and medical areas and in
      poly technical ones. Finally attention would be paid to the strategy for
      prevention, implementing ergonomic programmes, health surveillance, adequate
      training to work, aimed to primary prevention of WMSDs.

PMID- 11505782
TI  - Synthesis and evaluation of anticonvulsant activities of some new
      arylhexahydropyrimidine-2,4-diones.
AB  - In this study, some new 3-alkyl-6-arylhexahydropyrimidine-2,4-dione derivatives
      were synthesized as anticonvulsant agents. 6-Arylhexahydropyrimidine-2,4-diones
      which were used as starting materials in the synthesis of the compounds were
      prepared in acidic media by the cyclization of potassium cyanate and the
      appropriate ureido acids that were gained by the reaction of beta-aminoacids,
      malonic acid and ammonium acetate. The structures of the synthesized compounds
      were confirmed by UV, IR, 1H-NMR and elementary analysis. Their anticonvulsant
      activities were determined by maximal electroshock (MES), subcutaneous metrazol
      (scMet) and rotorod toxicity tests for neurological deficits. According to the
      activity studies, 3-arylalkyl-6-(p-chlorophenyl) derivatives were found to be
      protective against scMet, whereas 6-phenyl derivatives were not. 6-Phenyl-3-(2
      morpholinoethyl)hexahydropyrimidine-2,4-dione was the only compound determined to
      be active against MES at 300 mg/kg dose at half an hour.

PMID- 11505783
TI  - Endothelin receptor antagonist activity of (R)-(-)-2-(benzo[1,3]dioxol-5-yl)-N-(4
      isopropylphenylsulfonyl)-2-(6-methyl- 2-propylpyridin-3-yloxy)acetamide
      hydrochloride (PABSA) in rat aortic smooth muscle cells and isolated rat thoracic
      aorta.
AB  - Antagonist activities of (R)-(-)-2-(benzo[1,3]dioxol-5-yl)-N-(4
      isopropylphenylsulfonyl)-2-(6-methyl- 2-propylpyridin-3-yloxy) acetamide
      hydrochloride (CAS 188710-94-3, PABSA), a novel endothelin (ET) receptor
      antagonist, for ETA and ETB receptors were evaluated using rat aortic smooth
      muscle A7r5 cells and isolated rat thoracic aorta. PABSA concentration
      dependently inhibited the ET-1-induced increase in intracellular calcium
      concentration ([Ca2+]i) mediated via ETA receptors in A7r5 cells with an IC50 of
      0.17 nmol/l. PABSA antagonized the ETA receptor-mediated contraction induced by
      ET-1 in endothelium-denuded rat aorta with a Kb of 0.74 nmol/l. The potency of
      PABSA in inhibiting ETA receptor-mediated vasocontraction was approximately 40-
      and 100-fold greater than those of BQ-123, a selective ETA antagonist, and
      bosentan, a mixed ETA/ETB receptor antagonist, respectively. ETB receptor
      mediated endothelium-dependent vasorelaxation induced by ET-3 in the aorta was
      also antagonized by PABSA, with a Kb of 9.8 nmol/l. In contrast, PABSA affected
      neither the vasocontraction induced by KCl or norepinephrine nor the
      vasorelaxation induced by acetylcholine or prostaglandin I2 in the aorta. These
      results suggest that PABSA is a highly potent and selective ETA receptor
      antagonist.

PMID- 11505784
TI  - Synthesis and hypolipidemic activity of modified side chain alpha-asarone
      homologues.
AB  - A series of homologues of alpha-asarone (1), containing variable size and
      functionality on the side chain attached to the aromatic ring, has been subjected
      to a study of structure-activity relationship. For most of the prepared
      derivatives, either with a carbonyl (8a-8e), a hydroxy group (9a-9e), or with a
      conjugated double bond (10a-10d), significant effects on serum lipoprotein
      cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides were displayed.
      The results showed an enhancement of the hypocholesterolemic activity as the
      length of the chain is decreased. Theoretical conformational and electrostatic
      potential analyses of I and olefins 10 suggest unfavorable steric interactions in
      the bulky superior side-chain homologues as the deactivating biological effect.

PMID- 11505785
TI  - Antiulcerogenic effect of some gastrointestinally acting plant extracts and their
      combination.
AB  - Extracts from the plants Iberis amara, Melissa officinalis, Matricaria recutita,
      Carum carvi, Mentha x piperita, Glycyrrhiza glabra, Angelica archangelica,
      Silybum marianum and Chelidonium majus, singly and combined in the form of a
      commercial preparation, STW 5 (Iberogast) and a modified formulation, STW 5-II,
      lacking the last 3 constituents, were tested for their potential anti-ulcerogenic
      activity against indometacin induced gastric ulcers of the rat as well as for
      their antisecretory and cytoprotective activities. All extracts produced a dose
      dependent anti-ulcerogenic activity associated with a reduced acid output and an
      increased mucin secretion, an increase in prostaglandin E2 release and a decrease
      in leukotrienes. The effect on pepsin content was rather variable and did not
      seem to bear a relationship with the anti-ulcerogenic activity. The most
      beneficial effects were observed with the combined formulations STW 5 and STW 5
      II in a dose of 10 ml/kg b.w., comparable with cimetidine in a dose of 100 mg/kg
      b.w. The anti-ulcerogenic activity of the extracts was also confirmed
      histologically. The cytoprotective effect of the extracts could be partly due to
      their flavonoid content and to their free radical scavenging properties.

PMID- 11505786
TI  - Chlorite-hemoprotein interaction as key role for the pharmacological activity of
      the chlorite-based drug WF10.
AB  - WF10 is a chlorite-based drug that modulates macrophages functional states and
      can be safely administered to humans. WF10 potentially modulates disease-related
      up-regulation of immune responses both in vitro and in vivo. Thus immune response
      is influenced in a way that inappropriate inflammatory reactions are
      downregulated. The molecular mechanisms involved are not completely understood.
      Biochemical data suggest the reaction of chlorite with hemoproteins as the
      central step in the activation process of the drug. Thereby a chlorinating agent
      is generated, resulting in the oxidation of reduced sulfur-containing molecules
      and in the conversion of amino residues into more or less stable chloramines. The
      most prominent chloramine in vivo is taurine chloramine. Taurine chloramine is a
      long-lived molecule with immunomodulatory properties. For instance, taurine
      chloramine inhibits the generation of macrophage inflammatory mediators such as
      nitric oxide, prostaglandin E2 (PGE2), tumor necrosis factor alpha (TNF-alpha)
      and interleukin-6 (IL-6). This study on the biochemical mechanism of WF10 gives
      evidence that hemoprotein dependent chlorination of taurine is not only observed
      in vitro but also very likely in vivo. To characterize the oxidant, generated
      during heme activation, different methods were used: Chemiluminescence, EPR
      spectroscopy, UV/VIS-spectroscopy, gas (GC) and size exclusion chromatography. In
      summary, the results indicate as the first products of hemoprotein catalyzed
      chlorite activation a chloroxygen-species (probably HOCl/OCl-) and a ferryl
      oxygen species at the hemoprotein active site in analogy to the known peroxidase
      (compound I and II) intermediates. Moreover, hydrogen peroxide and chlorite seem
      to react in a similar way with heme centers. It is proposed that WF10 represents
      an "inactive" transport form of potentially active chlorine. Reactivity of the
      latter is restricted unless heme moieties in proteins or enzymes activate the
      "transport form" to perform reactions in analogy to peroxidases (i.e.
      myeloperoxidase-catalyzed formation of HOCl/OCl-).

PMID- 11505787
TI  - Efficacy of Echinacea purpurea in patients with a common cold. A placebo
      controlled, randomised, double-blind clinical trial.
AB  - Common colds are one of the most frequent acute illnesses with major economical
      impact. Echinaceae purpureae herba (Echinacin, EC31J0) has shown promising
      results in the relief of common cold symptoms and the time taken to improvement
      compared to placebo. This study was aimed to confirm these findings by performing
      a randomised, double-blind, placebo-controlled clinical trial. A total of 80
      adult male or female patients with first signs of a cold were recruited. The
      number of days of illness with a complete picture of the common cold (defined by
      the modified Jackson score of at least 5 points and experience of rhinorrhea
      and/or a subjective sensation of having a cold) was the primary end-point. In the
      verum group the median time of illness was 6.0 days compared to 9.0 days in the
      placebo group, assigning zero time for patients without a complete picture (one
      sided p = 0.0112). EC31J0 was well tolerated and clinically effective in
      alleviating symptoms more rapidly than placebo in patients with a common cold.

PMID- 11505788
TI  - Synthesis and anthelmintic activity of 3,6-disubstituted-7H-s-triazolo(3,4
      b)(1,3,4)thiadiazines.
AB  - A series of 3,6-disubstituted-7H-s-triazolo(3,4-b)(1,3,4)thiadiazines was
      synthesized by the condensation of the appropriate 3-substituted-4-amino-5
      mercapto (1,2,4) triazoles with substituted phenacyl bromides in alcoholic
      medium. These compounds have been studied for their in vivo anthelmintic activity
      in albino mice. A number of compounds showed promising activity when given by the
      oral route.

PMID- 11505789
TI  - In vivo toxicity, pharmacokinetic features and tissue distribution of N-[2-(2,5
      dimethoxyphenylethyl)]-N'-[2-(5-bromopyridyl)]-thiourea (HI-236), a potent non
      nucleoside inhibitor of HIV-1 reverse transcriptase.
AB  - N-[2-(2,5-Dimethoxyphenylethyl)]-N'-[2-(5-bromopyridyl)]-thiourea (HI-236, CAS
      233271-65-3) possesses potent anti-viral activity against zidovudine-sensitive as
      well as multidrug-resistant HIV-1 (human immunodeficiency virus) strains. The
      purpose of the present study was to examine in vivo toxicity, pharmacokinetic
      features and tissue distribution of HI-236 in mice. HI-236 had an elimination
      half-life of 85.8 min after i.v. administration and 86.6 min after i.p.
      administration. The systemic clearance of HI-236 was 4337 ml/h/kg after i.v.
      administration and 10,130 ml/h/kg after i.p. administration. Following i.v.
      injection, HI-236 rapidly distributed to and accumulated in multiple tissues with
      particularly high accumulation in lung, adipose tissue, skin, urinary bladder,
      adrenal gland and uterus + ovary. The concentration of HI-236 in brain tissue was
      comparable to that in the plasma, indicating that HI-236 easily crosses the blood
      brain barrier. Following i.p. injection, HI-236 was rapidly absorbed with a tmax
      values of 5.6 min and showed linear pharmacokinetics within the dose range of 10
      80 mg/kg. Following oral administration, HI-236 was absorbed with a tmax of 5.8
      min. The intraperitoneal bioavailability was estimated at 42.9%, while the oral
      bioavailability was only 2.2%. The pharmacokinetic study described herein
      provides the basis for advanced pharmacodynamic study of HI-236.

PMID- 11505790
TI  - Evaluation of cardiac subacute toxicity of ciprofloxacin in rats using serum
      biochemical parameters.
AB  - Cardiac subacute toxicity induced by ciprofloxacin (1-cyclopropyl-6-fluoro-1,4
      dihydro-4-oxo-7-(1-piperazinyl)-3-quinoline carboxylic acid, CAS 86393-32-0) a
      relatively new quinolone carboxylic acid derivative with an extensive
      antibacterial spectrum was investigated in healthy rats using serum biochemical
      parameters. Toxicological evaluation was performed in serum samples following the
      administration of the therapeutic dose regimens of the compound. Cardiac subacute
      toxicity was evaluated by measuring serum enzyme activity of creatine kinase,
      creatine kinase isoenzyme-MB (muscular-brain), lactate dehydrogenase and
      aspartate aminotransferase. The serum biochemical parameters indicated that the
      cardiac subactue toxicity of ciprofloxacin was: Cipro 1.2 (250 mg) = Cipro 2.4
      (500 mg) < Cipro 4.3 (750 mg).

PMID- 11505791
TI  - Efficacy of cetylpyridinium chloride used as oropharyngeal antiseptic.
AB  - Cetylpyridinium chloride, (CPC, CAS 123-03-5) as active ingredient of antiseptic
      oral mouthrinses has a broad antimicrobial spectrum with a rapid bactericidal
      effect on gram-positive pathogens and a fungicide effect on yeasts in particular.
      There are gaps in its effectiveness against gram-negative pathogens and
      mycobacteria. Application of CPC at a concentration of 0.05% as a mouthrinse
      results in an immediate reduction in bacterial counts of 2.0 to 2.5 log steps
      (which is adequate to > 99%). This reverts to about 1 log step (= 90%) 1 h after
      application. The ability of CPC to inhibit plaque and thereby reduce gingivitis
      is assured. In comparison to chlorhexidine, CPC has a lower residual effect, and
      as a result a lesser effect against plaque and gingivitis. The efficacy of CPC
      against oropharyngeal candidiasis is assured. CPC mouthrinses can significantly
      reduce infectious aerosols in dental practice, thereby protecting both staff and
      the patient. The balance of intra-oral bacterial flora is not disturbed even in
      the case of relatively long-term use of CPC (up to six weeks). Taking these
      properties into consideration, CPC may be considered as an alternative active
      ingredient in the case of chlorhexidine intolerance in the treatment and
      prevention of bacterial or fungal disorders of the oropharyngeal cavity. It is
      also of interest as an element for combination in the development of new types of
      oropharyngeal antiseptics.

PMID- 11505792
TI  - Pharmacokinetics of (-)-(S)-bromofosfamide after intravenous and oral
      administration in mice.
AB  - (-)-(S)-Bromofosfamide ((2S)-(2-chloroethylamino)-3-(2-bromoethyl)-1,3,2
      oxazaphosphorinane 2-oxide, CAS 146452-37-1, CBM-11) is a new potential anti
      cancer drug, currently under investigation. Its pharmacokinetics and
      bioavailability were studied in female mice following intravenous and oral
      administration of the dose of 50 mg/kg. The compound was extracted from plasma
      samples using chloroform and analyzed by high-performance liquid chromatography
      with UV detection at 200 nm. Orally administered (-)-(S)-bromofosfamide was
      absorbed quickly, attaining a maximum level of 33.9 micrograms/ml at 5 min, and
      was eliminated with a half-life (t1/2) of about 0.9 h. The average half-life of
      intravenously administered (-)-(S)-bromofosfamide was about 0.7 h. The total
      plasma clearance (CL) and volume of distribution (Vd) were found to be 0.14 l/h
      and 4.92 l/kg, respectively. The absolute bioavailability of (-)-(S)
      bromofosfamide after oral administration was 105%.

PMID- 11505793
TI  - Pharmacokinetics and toxicity of oral (-)-(S)-bromofosfamide in lung cancer
      patients.
AB  - The pharmacokinetics and toxicity of (-)-(S)-bromofosfamide ((2S)-(2
      chloroethylamino)-3-(2-bromoethyl)-1,3,2-oxazaphosphorinae 2-oxide, CAS 146452-37
      1, CBM-11) were determined in ten patients with non-small cell lung cancer
      following an oral dose of 1.38 g/m2 B.S.A. (Body Surface Area). The drug was
      given as a powder in gelatine capsules to fasting patients. Plasma samples were
      collected during the first 24 h after administration. All samples, after
      extraction with chloroform, were assayed by a reverse phase HPLC method using UV
      detection at 200 nm. Orally administered (-)-(S)-bromofosfamide showed relatively
      fast absorption kinetics. Peak concentration of 47 micrograms/ml was observed
      after 1 h. The average half-life was about 5 h. Toxicities associated with oral (
      )-(S)-bromofosfamide therapy consisted of symptoms regarding the central nervous
      system, gastrointestinal tract and urinary tract. Neurotoxic symptoms were the
      most common clinically significant side effects and probably dose limiting.

PMID- 11505794
TI  - Pharmacokinetics of human growth hormone administered subcutaneously with two
      different injection systems.
AB  - The bioavailability of recombinant human growth hormone (somatropin, CAS 12629-01
      5) was compared between a transcutaneous jet injection device and subcutaneous
      cannula injection. Thirteen healthy male subjects received 8.64 IU somatropin
      once with jet and once with cannula injection in a randomized cross-over study.
      Baseline-corrected somatropin serum concentrations were evaluated with non
      compartmental and compartmental methods. The 90% confidence intervals with two
      one-sided t-tests around the ratios of injection devices were 91-120% for maximum
      concentration, 94-110% for area-under-curve until 14 h, and 92-103% for area
      under-curve to infinity. Somatropin has a known metabolic half-life of ca. 20-30
      min while the observed terminal half-lives were 2-4 h. Absorption and elimination
      rate constants were similar. Times of maximum concentrations, terminal half-lives
      and lag times to start of absorption appeared to be shorter and the absorption
      rate constant appeared to be larger for jet than for cannula injection. In
      conclusion, the kinetics of somatropin from subcutaneous tissue had a "flip-flop"
      characteristic. Bioavailability of somatropin after jet injection was equivalent
      to cannula injection.

PMID- 11505795
TI  - [The content of biogenic amines in canned fish from the Turkish market].
AB  - This paper describes the determination of biogenic amines in a number of canned
      fish of the Turkish market by means of HPLC. Over all 39 cans of sardine, tuna,
      sardel, mackerel, pelamide and trout were tested. The determination of agmatine,
      cadaverine, histamine, putrescine and tyramine was performed by HPLC with post
      column derivatization with ortho-phthaldialdehyde. Four samples contained higher
      amounts of biogenic amines (three sardine samples contained more than 1000 mg/kg
      histamine) while all other samples were acceptable. These results demonstrate the
      need of instrumental analyses in the quality control system of Turkish producers
      of canned fish. The quality of the products at least of some producers has to be
      improved, e.g. by cooperation between the official food control and the quality
      assurance system of the producers.

PMID- 11505796
TI  - Classical swine fever (CSF): a historical review of research and vaccine
      production on the Isle of Riems.
AB  - A review on classical swine fever (CSF) research and vaccine production is given
      about four historical periods (1924-1948, 1949-1969, 1970-1991, since 1992).
      Similar as to research on foot and mouth disease, applied topics as diagnosis,
      pathogenesis, epidemiology and control represented the CSF research over many
      years. The development of vaccines and application procedures, e.g. oral and
      aerogenic immunisation and combined vaccines for large pig farms were the
      prominent investigations between 1950 and the middle of 1980s. After being
      reduced in the first years after affiliation to the Federal Research Centre for
      Virus Diseases of Animals, CSF is one of the main topics of the research on the
      Isle of Riems, not at least because nowadays the German National Reference
      Laboratory for CSF was established on the Island.

PMID- 11505797
TI  - Identification of different BLV provirus isolates by PCR, RFLPA and DNA
      sequencing.
AB  - A first attempt for the investigation of molecular epidemiology of BLV was
      carried out. PCR amplicons of a part of the env gene of BLV isolated from 309
      cattle of different geographical origin were compared with known BLV env
      sequences. Using RFLPA most of the PCR products can be assigned to the
      Australian, the Japanese or the Belgian subgroup. A phylogenetic tree resulting
      from the comparison of the sequences of these env fragments demonstrates the
      relations and differences between and within the subgroups.

PMID- 11505798
TI  - [The role of the kidneys in vitamin metabolism].
AB  - It is well established that the kidney plays an essential role in regulating the
      homeostasis of body fluids. Recent studies provided evidence for the kidney to be
      an important organ for the regulation in the metabolism of both fat (vitamin A,
      D) and water soluble vitamins (e.g. vitamin B12). This regulation is mediated by
      glomerular filtration as well as reabsorption and secretion processes of protein
      bound vitamins. Vitamin transport proteins such as retinol-binding protein,
      vitamin D-binding protein and transcobalamin II are filtered in renal glomeruli
      and subsequently reabsorbed in the proximal tubules by endocytosis from the
      tubular fluid. Megalin, a scavenger receptor belonging to the LDL receptor
      family, is probably the most important receptor in this process in the proximal
      tubule cells. The carrier proteins are degraded in lysosomes whereas the vitamins
      are probably stored, may become coupled to newly synthesized carriers and
      secreted at the basolateral plasma membrane. A renal vitamin excretion is
      observed in dogs and other species of the family Canidae, in form of fat soluble
      retinol and retinyl esters bound to Tamm-Horsfall protein. This and the high
      vitamin A concentrations in renal tissue of canines suggest an important role of
      the kidneys in vitamin A metabolism of these species.

PMID- 11505800
TI  - [Helminth findings in indigenous raccoon dogs Nyctereutes procyonoides (Gray,
      1843)].
AB  - Internal organs of 74 racoon dogs originating from the eastern districts of the
      Federal Land Brandenburg were subjected to a complete helminthological
      dissection. In addition, samples of diaphragma muscles from 46 further animals
      were examined for Trichinella larvae. Altogether 3 trematode- (Alaria alata,
      Isthmiophora melis, Metorchis bilis), 3 cestode- (Mesocestoides sp., Echinococcus
      multilocularis, Taenia polyacantha) and 7 nematode species (Capillaria aerophila,
      C. plica, Trichinella spiralis, Uncinaria stenocephala, Molineus patens,
      Crenosoma vulpis, Toxocara canis) could be identified. Thereby, the racoon dog
      has a comparable helminth spectrum as well known in red foxes. Differences in the
      frequency of the occurrence of helminths in both hosts can be explained by
      different food preferences.

PMID- 11505799
TI  - [Influence of changing oral mineral supply on kidney functions including renal
      fractional excretion of calcium, magnesium and phosphate in cows].
AB  - The influence of normal (100%), reduced (50%), or increased doses (200%) of
      mineral content in food on selected kidney functions and on serum values of
      calcium, magnesium, phosphate and osmolality was tested in cattle (n = 6; age: 3
      5 1/2 years; metabolic body mass: 106-132 kg0.75; non-pregnant, non-lactating)
      over 7 weeks. During the 19-day period of reduced mineral supply glomerular
      filtration rate, urine osmolality, 24-hour urine creatinine amount and serum
      electrolyte concentrations (exception: total magnesium) remained without
      significant deviations from the initial physiological values. In contrast to
      these results, the values of 24-hour urine volume, 24-hour urine osmolyte,
      serum/urine-ratio of creatinine, FECa and FEMg were significantly reduced. During
      the 15-day feeding period with over-supply of minerals the parameters 24-hour
      urine volume, serum/urine-ratio of creatinine, FECa, FEMg and FEPhosphate rose
      significantly. The proven influence of the supply with minerals on the renal
      electrolyte elimination can be used for the diagnosis of disturbances of mineral
      feeding in "kidney-healthy" cattle.

PMID- 11505801
TI  - [Pain and suffering in fish].
AB  - The question on the capability of fish to feel pain and of suffering are still
      subject of discussion nowadays. In the article presented, the information
      available in the literature to date is summarised. Based on this knowledge, the
      conclusion is drawn that fish are capable of feeling pain and that they are able
      to suffer in the sense of the word as used in the German animal welfare law.

PMID- 11505802
TI  - [The vegetarian appeal and killing animals. An ethical challenge].
AB  - The demand for renunciation of killing animals has already been discussed by
      mankind since ancient times. Many arguments for and against this demand have
      accumulated in the meantime. The reproaches of the vegetarians repeatedly forced
      the ones who eat meat to justify their diet. Today most of these historical
      justifications however have to be rejected because of lacking plausibility. Many
      of the vegetarian arguments on the other hand must be rejected for similar
      reasons as well. Remaining as morally convincing is the demand for doing the
      killing absolutely painless and without frightening the animals, which was
      already formulated for example by Kant and Schopenhauer. Arguments which consider
      this way of killing as still immoral belong in a broad sense to the
      "anthropocentric" animal ethics. They do not belong to what is called in Germany
      "pathocentric" animal ethics, because an animal that is killed without being
      frightened or tortured, has not suffered, for it hasn't consciously realized
      anything like danger or harm. We do even argue that these animals are not harmed
      at all, because it seems senseless to talk about harm without negative conscious
      phenomena. To push ahead a ban on animal slaughter for moral reasons could be
      itself morally wrong because it would disturb indirectly many people's conscious
      well-being without being justified by protecting an animal's conscious well
      being. It is however possible to derive from a general duty not to make animals
      suffer (pathocentric animal ethics) a duty to boycott food of animal origin if
      these animals had to suffer during their lives.

PMID- 11505803
TI  - Incidence of foreign-body-induced ileus in dogs.
AB  - While playing or simply because of avidity, dogs may ingest a variety of foreign
      bodies. Ingested foreign bodies, which are not stopped in the mouth or
      oesophagus, enter into the stomach. Once a foreign body has passed through the
      pylorus, jejunum and ileum appear to be the most common sites of the small
      intestine obstruction. The records of 103 cases, treated at the Clinic for
      Surgery, Orthopaedics and Ophthalmology of the Veterinarian Faculty, University
      of Zagreb from January 1981 till December 1998 were analysed. The analysis
      included the incidence of ileus caused by foreign bodies and the distribution of
      patients by sex, age, breed, duration of illness, site of obstruction, types of
      foreign bodies and the interrelation between these parameters. The results of our
      research show that the number of patients with foreign body induced ileus is
      increasing. Males ingested foreign bodies more often than females. Foreign body
      induced ileus was more frequently found in animals below 2 years of age. Foreign
      bodies were mostly ingested by mongrels, but also by popular dog breeds such as
      Dobermanns, Poodles, Cocker Spaniels and Rottweiler. Most of these ileus cases
      were found in March and October and the predominant clinical signs included
      anorexia, dehydration, abdominal tenderness and absence of defecation. The most
      common site of small intestine obstruction by foreign bodies was the jejunum, and
      the most effective treatment was enterotomy. Dogs mostly ingested stones, plastic
      and rubber objects. The treatment was more successful in dogs below 2 years of
      age. Patients that died post-surgically, died mostly the first day after surgery.

PMID- 11505804
TI  - [Factors influencing the content of urea in the milk of ewes].
AB  - In total records of 363 East Friesian breed of sheep and 15 Lacaunes from 15
      flocks located in Lower Austria, Upper Austria and Styria were available to
      investigate the influences on milk urea content. In one flock different groups of
      ewes were fed with low, medium and high amounts of energy and protein, but
      constant protein and energy ratio. The milk urea levels exhibited to
      statistically significant differences but the tendency of the feeding effect
      could be confirmed. Additional parameters influencing the urea content of milk of
      ewes are: herd specific factors, stage of lactation, mastitis, preservation and
      different analytical methods. The content of urea in milk is not suitable for
      assessment of the energy/protein-ratio of ewes with mastitis problems. Due to the
      special composition of sheep milk it is important to take account of the
      analytical method for determination of urea. Thus milk urea of one flock should
      be evaluated but not of individual sheep. In spite of these influence factors the
      determination of milk urea is a valuable tool for assessment of the energy and
      protein intake.

PMID- 11505805
TI  - Effect of allergen immunotherapy on soluble adhesion molecules.
AB  - The level of soluble adhesion molecules in the serum reflects the degree of
      systemic inflammation but the dynamics of these molecules in the pathogenesis of
      allergic diseases and their evolution during treatment, remains to be
      established. OBJECTIVE: To determine the evolution of the levels of soluble forms
      of serum intercellular adhesion molecule-1 (sICAM-1) and vascular cell adhesion
      molecule-1 (sVCAM-1) during immunotherapy to Dermatophagoides pteronyssinus in
      patients with allergic rhinitis and/or asthma. POPULATION: We included in this
      study 23 patients with perennial allergic rhinitis and/or asthma to
      Dermatophogoides pteronyssinus. 17 patients (6 males, 11 females, 13-48 years;
      mean: 27.2 years) were treated for one year with specific immunotherapy using
      standardized slow-release D. pteronyssinus extract (Lofarma, Milan, Italy). The
      other 6 patients (control group; 2 males, 4 females, 20-37 years; mean: 26.5
      years) received only symptomatic treatment. METHODS: Serum sICAM-1 and sVCAM-1
      were measured by ELISA method (R&D system). Blood samples were collected from
      each immunotherapy-treated patient at two timings: before immunotherapy (T0) and
      after one year of immunotherapy (T1). The two blood samples from each control
      patient (T0 and T1) were also collected one year apart. RESULTS: Before
      Immunotherapy (T0), the mean serum level of sICAM-1 was 336.0 ng/ml. After one
      year of immunotherapy (T1) it decreased to 325.2 ng/ml but this difference was
      not statistically significant. Mean serum level of sVCAM-1 was 655.5 ng/ml before
      immunotherapy (T0), decreasing significantly (p < 0.05) to 568.2 ng/ml (T1). In
      the control group both sICAM-1 and sVCAM-1 had no significant changes (sICAM-1:
      363.1 ng/ml (T0) and 374.7 ng/ml (T1); sVCAM-1: 611.5 ng/ml (T0) and 649.8 ng/ml
      (T1). CONCLUSIONS: These results suggest that specific immunotherapy with D.
      pteronyssinus induces a decrease in serum sVCAM-1 but not in sICAM-1 levels. The
      decreased expression of sVCAM-1 after immunotherapy is probably related to a
      decrease in the inflammatory reactions.

PMID- 11505806
TI  - Chronic mucocutaneous candidiasis revisited.
AB  - A study of 26 female patients with recurrent candidial infections have been
      studied. Delayed hypersensitivity to Candida antigens was observed only in 17 of
      the patients. 12 patients had also chronic urticaria. A defect in NK cells was
      found in 18 out of 23 cases (78%). Treatment with Candida vaccines had obtained
      good clinical results in 11 of the first 13 patients treated.

PMID- 11505807
TI  - Antihistamines and serum adhesion molecule levels.
AB  - BACKGROUND: Some antihistamines are capable of inducing decreased expression of
      adhesion molecules in nasal and conjunctival tissues of allergic
      rhinoconjunctivitis patients. This study aimed to determine if one month of
      therapy with loratadine 10 mg once daily would also induce any decrease in serum
      levels of soluble ICAM-1 (sICAM-1) or VCAM-1 (sVCAM-1). MATERIAL AND METHODS: 40
      monosensitized House Dust Mite (HDM) mild-to-moderate allergic rhinitis patients
      were included in the study. During the study, twenty patients randomly received
      10 mg loratadine daily, the other twenty did not take any antihistamine. All
      patients were treated with nasal budesonide daily and sodium cromoglycate nasal
      spray when needed. Serum soluble ICAM-1 and VCAM-1 levels were determined by
      immunoenzimatic assay before and in the end of the study period. RESULTS: After
      one month of loratadine sVCAM-1 levels had a significant decrease (from 724.8 to
      625 ng/ml) while sICAM-1 levels had a slight but not significant increase.
      Control patients did not have significant variations in sVCAM-1 or sICAM-1 serum
      levels. During regular antihistamine therapy patients improved their clinical
      scores. CONCLUSIONS: Loratadine 10 mg daily during one month induced a decrease
      in sVCAM-1 but not in sICAM-1 levels in HDM allergic rhinitis patients.

PMID- 11505808
TI  - Allergic rhinitis and asthma: more similarities than differences.
AB  - Clinical epidemiological and pathophysiological studies suggest a strong
      functional and immunological relationship between the nose and the bronchi. Nasal
      stimulation, can induce bronchoconstriction by a proposed rhinobronchial reflex
      and inflammatory mediators originating from the nose could be inhaled and trigger
      bronchial inflammation. Bronchial provocation in sensitised subjects results in
      nasal inflammation through systemic circulation. There is an increased prevalence
      of asthma in patients with rhinitis relatively to patients without nasal
      complaints and allergic rhinitis patients have an increased risk to develop
      asthma. Nasal and bronchial co-morbidity is high, 75% of asthmatics have rhinitis
      and 20% to 40% of rhinitic patient suffer from asthma. In the World Health
      Initiative on Allergic Rhinitis and its effect on Asthma (ARIA) it is quoted that
      asthma and rhinitis are common co-morbidities suggesting the concept of one
      airway one disease. The term allergy rhinobronchitis has been proposed to link
      the association between asthma and rhinitis. The treatment of rhinitis and
      sinusitis is important for management of asthma. Treatment of chronic rhinitis
      not only reduces nasal inflammation obstruction and discharge but also can reduce
      lower airway hyperesponsiveness and symptoms of asthma. Treating nasal
      inflammation is a key point in asthma control. These data strength the functional
      and allergologial link between nose and bronchi. Nasal inflammation induced by
      nasal challenge in patients with rhinitis has the ability to also induce
      bronchial changes in some asthmatic patients.

PMID- 11505810
TI  - [Priapism: decisional algorithm, our experience, and role of sildenafil in sexual
      rehabilitation].
AB  - OBJECTIVE: We report our experience in the management of priapism. MATERIALS AND
      METHODS: In a 2-year period we observed 7 patients of whom 4 presented with low
      flow and 3 with high flow priapism. RESULTS: In 2 of the patients with ischemic
      priapism, simple blood aspiration from the corpora allowed for a quick
      detumescence, while in the other 2 cases a derivative intervention (1 spongio
      cavernous and 1 glans cavernous) had to be performed. In all the 3 patients with
      high flow priapism we performed a superselective arteriography that obtained the
      visualisation of the arteriovenous fistula. These patients restarted their sexual
      activity after about three months. At six months a patient with low flow priapism
      restored sexual activity due to sildenafil 50 mg. CONCLUSION: The importance of
      distinguishing low and high flow priapism was confirmed.

PMID- 11505809
TI  - [Antioxidant therapeutic efficiency after the use of carnitine in infertile
      patients with bacterial or non bacterial prostato-vesiculo-epididymitis].
AB  - OBJECTIVE: In the male genital tract, reactive oxygen species (ROS)
      overproduction generated by infiltrating WBC or spermatozoa is one of the major
      causes of defective sperm function. Recently, we demonstrated that prostato
      vesiculo-epididymitis (PVE) is the male accessory gland infection more crucial
      for the establishment of this cellular (sperm and/or WBC oxidative) response.
      This biochemical stress is due to an imbalance of pro and antioxidants factors
      and persists even after treatment with antimicrobials. Thus, the antioxidative
      properties of Carnitines (in terms of combined "Carnitine-Acetil-Carnitine"
      system) have currently found more attention as part of antimicrobial therapies.
      In this study, we compared which antioxidative strategy was more beneficial for
      the treatment of PVE. MATERIALS AND METHODS: We selected two groups of infertile
      patients. One group consisted of 55 abacterial PVE patients (mean age 34 yrs,
      range 27-40) (group A); the other included other 35 bacterial PVE patients (mean
      age 35 yrs, range 28-38) (group B). Each group was randomly subdivided into the
      following treatment subsets: 1) A1 (n = 14) and B1 (n = 23) subsets received
      respectively a combined antibiotic and/or antiphlogistic regimen (x 14 days/
      monthly x 3 months) (first step) followed by L-Carnitine 1 g x 2 day + acetyl
      Carnitine 0.5 g x 2/day x other 3 months (second step) and finally no drug x
      other 3 months (third step). 2) A2 (n = 8) and B2 (n = 16) subsets received, for
      a 3 month period, in the meantime the combined antibiotic and/or antiphlogistic
      regimen (x 14 days/monthly) and L-Carnitine 1 g x 2/day + acetyl-Carnitine 0.5 g
      x 2/day (first step) and finally no drug x other 3 months (second step). 3) A3 (n
      = 8) and B3 (n = 12) subsets received for a 3-month period L-Carnitine 1 g x
      2/day + acetyl-Carnitine 0.5 g x 2 day (first step) and finally no drug x other 3
      months (second step). Before and after each step of the therapeutical design, all
      patients underwent semen and quantitative bacteriological analyses and 60/90
      semen specimens were also investigated about ROS production analysis by
      chemiluminescence in their 45% and 90% Percoll-generated fractions. RESULTS: The
      antioxidative response either in terms of significant decrease in the ROS
      production and increase in some semen parameters (sperm motility and viability)
      were highest in the patients of A1/B1 subsets, followed by A2/B2 subsets and
      lowest in the A3/B3 subsets. CONCLUSION: These results indicate that in PVE
      patients antimicrobials and/or antiphlogistic drugs get a full positive
      antimicrobial response but a partial antioxidative response, which seems to be
      potentiated by the addition of antioxidative agents (Carnitines). Furthermore, it
      is important to underline that the antioxidative treatment with Carnitines
      administered in the meantime with antiinfectious agents is less effective, and
      finally this treatment is unsuccessful without the eradication of the pro-oxidant
      (germs and WBC) agents.

PMID- 11505811
TI  - [Needle aspiration testicular cytology as diagnostic parameter in the assessment
      with varicocele].
AB  - OBJECTIVE: Varicocele is considered the most common cause of male infertility.
      The pathogenesis of the spermatogenetic impairment in this disease is not
      completely understood and the seminal patterns of patients with varicocele are
      different. Testicular fine-needle aspiration cytology (FNAC) in infertile men
      allows us to obtain many information about the type and the degree of alteration
      of the seminiferous tubule. MATERIALS AND METHODS: In this study, 200 infertile
      men with varicocele were evaluated for seminal parameters, FSH, LH and
      testosterone plasma concentrations. Testicular pattern was analyzed by bilateral
      FNAC. All patients suffered of infertility for at least two years and varicocele
      was the sole infertility-related pathology. According to the tubular patterns, we
      divided the patients into five groups, and we observed that the different tubular
      alterations could be present in patients with similar FSH levels and similar
      sperm count. Then, to verify the role of tubular pattern as prognostic factor for
      the correction of varicocele, we studied 70 men, performing seminal analysis and
      hormonal evaluation six months after sclerotherapy. RESULTS: We found an
      increasing in sperm count and in other seminal parameters after the sclerotherapy
      (motility, normal morphology...) only in patients with maturative alteration at
      spermatid level. This alteration of spermiogenesis seems to be reversible after
      sclerotherapy. CONCLUSION: In the light of these results the testicular FNAC
      gives important prognostic parameters in the selection of patients affected by
      varicocele for sclerotherapy.

PMID- 11505812
TI  - [Endourologic treatment of benign uretero-intestinal stenosis in patients with
      definitive urinary diversion: 10-year experience].
AB  - OBJECTIVE: Ureterointestinal (U-I) anastomotic stricture is one of the most
      important complications after radical cystectomy, occurring in 4% to 8% of
      patients. We report our ten years experience in the endourological treatment of
      this condition. MATERIALS AND METHODS: 32 patients with U-I strictures were
      endourologically treated at our Institution. The endoscopic procedure provides
      for a percutaneous nephrostomy, the passage of the stenosis with a guide-wire,
      the incision and balloon dilation of the stricture and, finally, a ureteral
      double J stenting. Of the 28 successfully treated patients, 10 underwent balloon
      dilation alone and 18 both ureteral incision (with cold knife in 11 and hot knife
      in 7) and dilation. RESULTS: The endourological approach failed in 4/32 (12.5%)
      patients: 3 failures were due to the inability to pass a guide-wire across the
      stricture, whilst in the remaining patient a serious intraoperative hemorrhage
      occurred. In 28/32 (87.5%) patients the endoscopic treatment was successful (a
      ureteral stent was positioned across the stenosis). However, long term results
      are less promising: at 6-90 month follow up, only 16 patients (57.1%) are free of
      strictures without ureteral stent, 10 (35.7%) need a permanent ureteral stent, 2
      (7.2%) a percutaneous nephrostomy. CONCLUSION: Due to the low morbidity of
      endoscopic procedures and to the high risks associated with open surgery, we
      believe that endourology should represent the first choice in the treatment of U
      I strictures, reserving open surgery for endoscopic failures or complications.
      Moreover, endourological treatment with both incision and dilation is more
      effective than dilation alone (which should be performed only in very short and
      recent strictures).

PMID- 11505814
TI  - [TESE-ICSI in the treatment of secretory azoospermia secondary to cryptorchism.
      Report of a clinical case].
AB  - The pathogenic role of cryptorchism in male infertility is still controversial.
      To report a case of a 34-year-old patient consulted for primary infertility with
      a history of 2 years associated with prepubertal bilateral orchidopexy for
      cryptorchidism. The fertility studies demonstrated azoospermia and normal sperm
      volume. Testicular sperm extraction (TESE) and intracytoplasmic sperm injection
      (ICSI) were performed with success. Cryptorchism can cause primary obstructive
      infertility. Testicular sperm aspiration (TESA) is an alternative when
      spermatogenesis is preserved. In this patient TESE-ICSI was performed with
      success.

PMID- 11505813
TI  - Effect of glycemia status on endocrinological parameters of impotent and
      infertile patients.
AB  - OBJECTIVE: To identify the effects of glycemia status on hormone levels, we
      evaluated the effects of hypo and hyperglycemia on endocrinological parameters of
      patients with erectile dysfunction, infertility, varicocele and compared the
      results with control subjects. MATERIALS AND METHODS: Twenty patients with
      erectile dysfunction, 20 infertile patients with oligo-azoospermia, 20 patients
      with normozoospermic left varicocele and 15 healthy control subjects constitute
      our study population. Plasma follicle-stimulating hormone (FSH), luteinizing
      hormone (LH), testosterone (T) and prolactin (PRL) levels were measured both in
      patients in hypoglycemia and hyperglycemia status. Statistical analysis were done
      by Wilcoxon test. RESULTS: All endocrinological parameters did not show any
      statistically significant difference between the hypoglycemia and hyperglycemia
      status. Also, no abnormalities in the endocrinological parameters were observed.
      CONCLUSION: We showed that the glycemia status of the patient (either hypo or
      hyperglycemia) did not effect the results of endocrine profile. Also, endocrine
      evaluation is unnecessary in impotence and infertility.

PMID- 11505815
TI  - [Exogenous risk factors for parenchymal carcinoma of the kidney].
AB  - In the last decades incidence rates for renal cell carcinoma have been constantly
      increasing, especially in western European and Scandinavian countries and North
      America. Several epidemiological studies observed an increased relative risk of
      this tumour linked with some exogenous and/or environmental factors. The
      following exposures have been more consistently associated with renal cell
      carcinoma: tobacco smoking; occupational exposures (asbestos, aromatic
      hydrocarbons, chemical solvents); dietetic factors such as high energy intake,
      consumption of fried meats and poultry, and reduced intake of fruit and
      vegetables; iatrogenic factors such as analgesics and amphetamines; common
      diseases like obesity and hypertension. An effective preventive strategy for
      renal cancer could be carried out reducing the exposure to such risk factors.

PMID- 11505816
TI  - [Evaluation of late results of reconstructions of the thumb by trimmed great toe
      method].
AB  - Twelve patients with posttraumatic defects of the thumb were treated in the years
      1990-1999 by the trimmed great toe method. Eight of them had additional injuries
      or loss of long fingers (two patients lost all fingers). Reconstruction methods
      were chosen basing on the amputation level. A fragment of the trimmed great toe
      of an appropriate length was used distally to the distal part of the first
      metacarpal according to the technique described by Wei (9 patients). In cases of
      a more proximal amputation only a distal part of the great toe was used.
      Pollicisation of other elements of the index with simultaneous free transfer of
      the great toe distal part was carried out in two patients with index amputations.
      Bone stabilization was secured by K wires. Arthrodesis was performed in three
      patients. Tendons were sutured in eight patients In every case anastomosis of the
      dorsal pedis artery, saphenous vein and two toe digital nerves were performed
      (additionally the toe plantar artery was anastomosed in two patients and branches
      of the superficial peroneal nerve were anastomosed in seven patients).
      Immobilization was applied for four weeks on the foot and six weeks on the hand.
      All the transferred trimmed great toes survived completely. The hand wounds
      healed after two weeks, the foot wounds 2-7 weeks (twenty eight days on average).
      Late results were evaluated 1-9 years after reconstruction. 2PD was 6-14 mm.
      Thumb length was similar to the contralateral ones and the average range of
      motion in i.p. join was 3 degrees. According to the patients the results were
      very good.

PMID- 11505817
TI  - [Surgical treatment of upper extremities of cases arthrogryposis multiplex
      congenita].
AB  - Between 1990-1999 at the Polish-American Pediatric Institute 36 children with
      arthrogryposis were treated. In 10 cases 21 corrective surgical procedures of the
      upper extremities were performed. Corrective procedures of the upper extremities
      were performed. Corrective procedures aimed at contractures of the hand, wrist
      and forearm, consisting of capsulotomies, lengthening of the finger flexor
      tendons and transposition of wrist flexor on to the wrist extensors were
      performed 8 times. Correction of extension contracture of elbow joint, consisting
      of posterior capsulotomy and lengthening of the triceps tendon was performed 9
      times. In 4 cases transposition of the pectoralis major onto the biceps tendon
      according to Clark or Zancolli in Carrol's modification was performed. The
      average age of the children was 4.7 years (age ranging from 1.5 to 9 years), the
      follow-up period was 4.25 years (ranging from 0.5 to 10 years). Palmer
      contracture of the wrist was an average 80 degrees (70-90 degrees) before
      surgery. Passive flexion in the elbow joint was on average 15 degrees (0-35
      degrees). Active flexion of the elbow was absent in all cases. After corrective
      procedures in the wrist, in 5 cases physiological positioning of the was
      achieved. After lengthening of the triceps tendon passive flexion of elbow was 80
      90 degrees, in one extremity 70 degrees. After the Clark or Zancolli procedures
      active flexion of the elbow was 80 degrees in one case, 70 degrees in another and
      50 degrees six months post-op. The author's own experiences indicate that and
      multi-stage interdisciplinary approach in necessary from the beginning in these
      cases.

PMID- 11505818
TI  - [The influence of the amount of variation of cervical-thoracic angle on the hip
      status and radiological results of the treatment of developmental hip dysplasia
      by torsion osteotomy].
AB  - The aim of this paper was to determine the differences in hip remodeling and
      final outcomes of hip dysplasia treatment by fixing a certain amount of varus
      during varus-detorsion osteotomy of the proximal femur. The analysis included 33
      children who underwent 48 osteotomies. During final follow-up at skeletal
      maturity it was found that the amount of varus fixed during the osteotomy
      influenced significantly femur remodeling and some containment measurements.
      However it played only slight part in acetabular remodeling. The outcomes at
      final follow-up proved significantly better in the group in whom a greater amount
      of varus was fixed.

PMID- 11505819
TI  - [Clinical and radiological evaluation of the hip joints treated operatively due
      to Perthes disease with incongruence of articular surfaces].
AB  - The aim of the study was the clinical and radiological evaluation of the hip
      joints treated operatively due to Perthes disease with incongruence of articular
      surfaces. 35 patients (37 hips) treated between 1988-1990 by means of proximal
      femoral and transpelvic osteotomy were evaluated. Average age of the child at the
      time of the operation was 7 years 3 months (5-10 years), and at the final
      examination 15 years (12-19 years). The average follow-up period was 7 years 7
      months (5-9 years). At the clinical examination there were 46 percent excellent
      results (17 hips), 32 percent good (12 hips), and 22 percent fair results (8
      hips). Radiological examination showed 19 percent excellent results (7 hips), 35
      percent good (13 hips), 5 percent of fair (2 hips), and 41 percent of poor
      results (15 hips). This study proved that the described operative treatment
      appeared a useful method in Perthes disease with incongruence of articular
      surfaces.

PMID- 11505820
TI  - [Intertrochanteric fractures of the hip treated with dynamic hip screws (DHS)].
AB  - The history and concept of sliding fixation is presented. Treatment results of 72
      cases with 76 intertrochanteric fractures treated with DHS were analysed.
      Fractures were classified according to the Kyle scale into 4 different types. 61
      males and 11 women age ranging from 46 to 72 years (average age: 65 years) were
      treated surgically. In 48 cases good results were achieved, in 22 cases results
      were satisfactory and in 6 cases results were poor. The use of DHS screws is an
      effective way of treating intertrochanteric fractures among patients with
      osteoporosis, as well as young patients requiring anatomic reduction of bone
      fragments. This technique allows early mobilization and weight bearing.

PMID- 11505821
TI  - [The possibilities of operative treatment of residual and recurrent congenital
      clubfoot].
AB  - The paper presents 14 different surgical procedures recommended in literature for
      the correction of singular deformed elements of congenital clubfeet. Basing on
      clinical material collected from patients treated during the last five years, the
      authors introduce the application of the presented procedures for the correction
      of residual and recurrent deformities occurring in congenital clubfeet. Basing on
      their own experience, knowledge and available publications the authors attempt to
      assess the indications for each particular procedure and their mutual
      connections, which depend on: the kind and extend of the deformity, its location
      and the age of the child.

PMID- 11505822
TI  - [Posteromedial release combined with peritalar release in the treatment of
      congenital clubfoot].
AB  - Basing on the authors' own experiences an attempt to assess the value of
      posteromedial release in treatment of congenital clubfoot was made. The procedure
      was performed in 70 feet in 52 children, age ranging from 6 months to 12 years,
      90% of the procedures were performed before 4 years of age. Feet were classified
      as follows: a. non-coerrective--type III according to Marciniak, b. Partially
      corrective, c. in older children (> 4 years of age) in whom posteromedial release
      was combined with a lateral resection of the cuboid bone. Late results after 5-20
      years (13 years on average) were assessed according to Magone's classification.
      Deformity free, fully functional feet were achieved in 60% cases. The authors
      stress the fact that posteromedial release is the method of choice in
      uncorrective cases of clubfeet, and in cases were conservative treatment was
      implemented after 10 months of age. In the procedure should be performed at the
      age of 2-3 months.

PMID- 11505823
TI  - [Long-term results of posteromedial release for the treatment of congenital
      clubfoot].
AB  - The aim of this paper was to evaluate long-term results of posteromedial release
      in the treatment of congenital clubfoot in 46 patients (61 clubfeet) treated at
      the author's institution between 1979 and 1990. The average follow-up period was
      15.7 years (from 20.4 to 10.1 years). The average age at the time of surgery was
      12.3 months (from 5 to 48 months). The final evaluation based on Magone et al.
      criteria gave the following results: excellent in 17 feet (28%), good in 17 feet
      (28%), fair in 11 feet (18%) and poor in 16 feet (26%).

PMID- 11505824
TI  - [The historical evolution of one-stage surgical treatment of congenital clubfoot
      in newborns].
AB  - The author presents a historical overview of the evolution of surgical treatment
      of congenital clubfeet, focussing in particular on the last 30 years. The paper
      reviews the pathological and biomechanical problems related to the surgical
      procedures introduced by Turco, McKay and Simons, as well as indications for
      procedures from a postero-lateral and Cincinnati approach.

PMID- 11505825
TI  - [Principles of choice of primary operative techniques for congenital clubfoot].
AB  - Review article. A definition of the congenital clubfoot as the rotational and
      torsional disorder in the sagittal, coronal and horizontal plane was described.
      The method of choice of the operative technique on the basis of clinical and
      radiographic parameters was presented. It was found that the primary technique
      used for surgical clubfoot correction is chosen from a set of different
      procedures, ranging from posterior release to complete subtalar release. The
      technique can be extended and modified during surgery.

PMID- 11505826
TI  - [One stage total thumb reconstruction using MP II joint pollicisation] and free
      transfer of distal part of great toe: report of two cases].
AB  - Indications, treatment and late results of thumb reconstruction in two males aged
      28 and 29 are presented. The thumbs had been amputated on the level of the middle
      first metacarpal with concomitant amputation in the middle of proximal phalanx of
      the index. Besides, one of the patients lost all other fingers in this hand.
      Reconstructions of the thumbs were carried out in the third and sixth months
      after the injury using pollicisation of the index stump and transferring free
      distal part of the trimmed great toe. FHL and EHL tendons were left intact. Some
      complications were observed in one of the patients. The complications included:
      spasm of the vein in the recipient site on the second day after the operation,
      wound dehiscence on the foot on the tenth day and nonunion of the index phalanx.
      Another surgery using bone graft was necessary. Grip reconstruction in one
      patient with metacarpal hand needed additional two toes to hand transfer. Results
      of the treatment were evaluated 8 and 6 years after the reconstruction. The new
      reconstructed thumbs were very similar to those on the contralateral hands with
      good sensation and sufficient movement (40 and 60 degrees of the flexion) to
      obtain strong and precise grip.

PMID- 11505827
TI  - [Anterior traumatic dislocation of the shoulder in children].
AB  - The authors present two cases (two boys, aged 11.5 and 13.5 years) with traumatic
      dislocation of the shoulder following traffic accidents. Proper diagnostic
      management and closed reduction gave good final results. A review of literature
      on this type of dislocation, rarely seen in children is presented.

PMID- 11505828
TI  - [Wound healing and healing disorders after removal of third molars].

PMID- 11505829
TI  - [Evidence-based dentistry].

PMID- 11505830
TI  - [Management of aneurysms of the hepatic artery. 15 patients].
AB  - OBJECTIVES: There appears to be an increasing number of patients with aneurysm of
      the hepatic artery. We report a retrospective analysis of management schemes used
      in a single hospital unit over the last 14 years. PATIENTS AND METHODS: Clinical
      data on all patients with aneurysm of the hepatic artery, treated in Edouard
      Herriot hospital (Lyon, France) from 1985 to 1999, were reviewed. RESULTS: There
      were 15 patients with 16 aneurysms. Mean patient age was 56 years with no gender
      predominance. The aneurysm was a fortuitous discovery in 8 of the patients. There
      were 10 cases of pseudoaneurysm and 6 cases of true aneurysm. Treatment was
      adapted to the local anatomy and the patient's status. Surgery was used for 5
      patients and radiologic embolization for 4. Observation was indicated in 5
      patients and spontaneous thrombosis occurred in 1. Mean duration of observation
      was 24 months. Six patients were lost to follow-up and 2 died from their primary
      disease. DISCUSSION: Surgery is the treatment of choice for aneurysms situated in
      an extrahepatic localization while radiologic embolization is appropriate for
      intrahepatic localizations. Close cooperation between the surgery and radiology
      teams was most contributive to proper management in our series, providing
      favorable outcome.

PMID- 11505831
TI  - [Immunologic response to antiretroviral treatment with combined stavudine,
      didanosine and nevirapine].
AB  - OBJECTIVE: The purpose of this study was to investigate the restoration of immune
      function in patients given two nucleoside-analogs and one non-nucleoside-analog
      (nevirapine). PATIENTS AND METHODS: The study was carried out in 27 HIV-1
      infected patients, starting a treatment with d4T, ddl and nevirapine, included in
      the VIRGO trial and followed up to 52 weeks. RESULTS: Total CD4 T cells increased
      as early as the fourth week of treatment (+154/microliter, p < 0.001) with a gain
      maintained until week 52 (+201/microliter at week 52). A similar pattern was seen
      for memory CD4 T cells (+80/microliter at week 4, +110/microliter at week 52).
      The rise in naive CD4 T cells was slower, strongly significant for week 16 (p <
      0.001) and maximum at week 24 (+105/microliter). DISCUSSION: In our study, rise
      in T cells was not correlated with virological response, however increase in
      total and naive CD4 T cells was correlated with the CD4 count at onset of therapy
      (p < 0.05). Our data indicate that patients on d4T-ddl-nevirapine therapy have
      the same immune restoration as patients given protease inhibitor-based regimens.

PMID- 11505832
TI  - [Leiomyoma of the esophagus].
AB  - BACKGROUND: Leiomyoma is a benign tumor rarely occurring in the esophagus. Only
      1% of esophageal tumors are leiomyomas. CASE REPORT: A 70-year-old man underwent
      surgery for an asymptomatic tumor of the thoracic esophagus. The tumor was
      enucleated via right thoracotomy and histology confirmed the diagnosis of
      leiomyoma. Outcome was favorable. DISCUSSION: Leiomyomas of the esophagus
      generally develop from the muscularis and exceptionally from the muscularis
      mucosae, producing a parietal tumor or a pediculated endoluminal tumor
      respectively. Surgery is indicated for all cases, with the possible exception of
      asymptomatic leiomyoma. Encleation can be achieved by videothoracoscopy.
      Resection of the esophagus can be discussed if enucleation is impossible for
      giant tumors, or ring tumors at the esogastric junction, or if the mucosae wound
      cannot be repaired. Endoscopic resection is indicated for pediculated leiomyoma.
      Malignant transformation is exceptional but an association between esophageal
      myomatosis and carcinoma of the esophagus is possible. Certain authors thus
      advocate resection for all cases, even small asymptomatic leiomyomas.

PMID- 11505834
TI  - [Chilaiditi syndrome].

PMID- 11505833
TI  - [Varicella zoster virus infection after bone marrow transplant. Unusual
      presentation and importance of prevention].
AB  - BACKGROUND: Leukemeia and lymphoproliferative disease are associated with a high
      risk of varicela-zoster virus (VZV) infection. Although infrequent, visceral
      involvement can be fatal. We report two cases of patients presenting severe VZV
      infection after bone marrow transplantation. CASE REPORTS: The first patient was
      a 42-year old man who received an allogeneic bone marrow transplantation for
      chronic myelogenous leukemia. A severe graft-versus-host reaction occurred. Three
      months after discontinuing VZV prophylaxis, VZV transverse myelitis was
      diagnosed, leading to death despite prompt treatment with acyclovir. The second
      patient was a 42-year-old woman treated with autologous bone marrow
      transplantation for lymphoma. She developed acute viral pancreatitis one month
      after discontinuing VZV prophylaxis. Recovery was achieved with intravenous
      treatment. DISCUSSION: These two cases illustrate the potential gravity of VZV
      infection after bone marrow transplantation. These observations point to the need
      for revisiting the duration of VZV prophylaxis.

PMID- 11505835
TI  - [Elderly hospitalized patients and drug compliance. Level of independence?].

PMID- 11505836
TI  - [Vesico-ureteral reflux and nephropathy in the child: medical or surgical
      treatment?].

PMID- 11505837
TI  - [Carotid stenosis: endarterectomy or angioplasty?].

PMID- 11505838
TI  - [Budgetary principles applying to the hospital].

PMID- 11505839
TI  - [Alcoholic liver cirrhosis. Screening for hepatocellular carcinoma in liver
      cirrhosis].
AB  - HIGH INCIDENCE: Because of the high incidence of hepatocellular carcinoma (HCC)
      in patients with cirrhosis (3 to 5% per year) and the fact that curative
      treatment is currently available only for small sized tumors careful screening is
      warranted in this high risk population. Earlier screening attempts produced
      disappointing results in terms of cure and survival, particularly in Europe.
      Progress in ultrasonography, a better understanding of the risk of developing
      HCC, and most importantly the advent of local percutaneous treatments have
      greatly affected the data which should be reexamined. SCREENING METHODS: Patients
      with cirrhosis, particularly alcoholic or viral cirrhosis, should undergo regular
      ultrasound examinations, every six months for most screening protocols although
      the best timing remains unknown. Assay of serum alpha-fetoprotein is of limited
      use due to its low sensitivity and specificity. Diagnosis of HCC is basically
      based on helicoidal computed tomography and/or magnetic resonance imaging
      findings, with or without pathological proof (ultrasound-guided biopsy) that may
      be difficult to obtain. A probabilistic diagnosis is therefore retained if
      necessary, based on the presence of risk factors and arterial
      hypervascularization of a liver nodule. EARLY TREATMENT: With ultrasound
      screening, the diagnosis of HCC can generally be established early, when curative
      transplantation, resection or local percutaneous destruction are still feasible.
      The percutaneous methods use chemical or physical agents to destroy the tumor.
      There are few contraindications so curative treatment can be proposed for large
      number of patients. Large-scale prospective studies will be completed in the
      upcoming years and are expected to provide evidence validating the principle of
      screening and early treatment.

PMID- 11505840
TI  - [Alcoholic liver cirrhosis. Treatment of hepatocellular carcinoma].
AB  - TRANSPLANTATION AND RESECTION: Surgery is still the only curative treatment of
      hepatocellular carcinoma (HCC). For patients with cirrhosis, liver
      transplantation for HCC with one nodule less than 5 cm in diameter, or no more
      than three nodules each less than 3 cm, gives the best results with a 5-year
      survival rate of 70%. Resection of a single tumor for patients with good liver
      function may also be performed with curative intent but the rate of recurrence is
      high. OTHER TECHNIQUES: Cryotherapy and radiofrequency are in-situ destruction
      methods used for small tumors. In the future, these procedures may compete with
      hepatic resection. When used alone, intra-arterial treatments, such as
      chemoembolisation, have only a palliative intent, but they also may be combined
      with other procedures. The treatment of advanced HCC is still limited and there
      is no standard approach for its management. HCC WITHOUT CIRRHOSIS: For those with
      HCC without cirrhosis, the same treatments are available but resection is more
      often performed because of the ability of the liver to regenerate. The management
      of patients with HCC with or without cirrhosis may combine several treatment
      modalities and needs a multi-disciplinary approach.

PMID- 11505841
TI  - [Comments on Thomas Mann and medicine].

PMID- 11505842
TI  - [James Joyce and the physicians].

PMID- 11505843
TI  - [Fighting the "ghost of darkness". Nietsche's suffering in it's psycho-physical
      correlation].

PMID- 11505844
TI  - ["I cannot live like you". Personal record of vulnerability and schizophrenic
      psychosis].

PMID- 11505845
TI  - [Animal-derived feeds as possible vectors for bovine spongiform encephalopathy
      (BSE) in Germany. 1. Comparative risk assessment for a single animal food of
      animal origin].
AB  - The occurrence of BSE cases in Germany after the ban of meat and bone meal for
      ruminant feed in 1994 requires a detailed investigation of animal derived
      feedstuffs regarding their specific risks as vectors for the disease. Accepting
      the theory that BSE is a prion transmitted disease, the theoretical infectious
      potential was calculated for animal derived feedstuffs. This calculation was
      based on the assumption, that risk material (brain, spinal cord) of one
      clinically diseased cattle was rendered in the process as established in Germany
      (133 degrees C, 3 bar, 20 min) or, alternatively, that one diseased animal was
      slaughtered resulting in normal processing of the by-products for human food
      production. From this risk assessment it became obvious that meat and bone meal
      was one, but probably not the most important source for the spreading of BSE.
      Taking into account the high sensitivity of calves it can be speculated that
      certain products, e.g. from bone processing (bone meal) and fat melting (mixed
      animal fats), commonly used for the formulation of milk replacers, might have
      been more important as pathways. As it can't be excluded retrospectively that
      infected meat and bone meal was imported from the UK, this non-calculable
      influence may have been related to the significance of the other products. The
      calculation model underlines that efficient removal of specified risk material
      (brain, spinal cord) and adequate processing (133 degrees C, 3 bar, 20 min) or
      alternatively other equivalent treatments of fats are prerequisites for
      minimising the risk of feed borne transmission of BSE by animal derived
      feedstuffs. The epidemiological consequences are part of a subsequent paper.

PMID- 11505846
TI  - [Eradication of paratuberculosis in dairy herds: determination of the initial
      herd prevalence and modelling of prevalence development].
AB  - A prerequisite for the success of any eradication programme is the accurate
      determination of the initial herd prevalence as well as a herd-specific
      prediction of prevalence development. This prerequisite is not currently given
      for the eradication of paratuberculosis in infected herds. In the work presented
      a method to predict the initial paratuberculosis prevalence in infected herds is
      presented; it is based on the formation of two groups (ELISA-positive and
      negative) and the determination of generally applicable factors (positive
      predictive value [ppvn] of the ELISA and sensitivity of fecal culture in the
      ELISA-negative group [senF]). The ppvn of the ELISA was determined to be 0.6
      based on the cultural examination of the ileocaecal lymph node of 64 ELISA
      positive animals; the value for senF was set to be 0.64 based on the cultural
      examination of feces and ileocaecal lymph nodes of 40 ELISA-negative animals. To
      calculate the initial herd prevalence the number of animals in each of the groups
      was multiplied with the ppvn of the ELISA or with the reciprocal value of senF
      (1.5). The values were added and divided by the size of the herd. The
      practicability of this model was examined on nine herds with a total of 708
      animals. The development of herd prevalence was modelled based on the examination
      scheme given in the paratuberculosis control programme of the "Niedersachsische
      Tierseuchenkasse" (local board for infectious disease control in food animals in
      the state of Lower Saxony, Germany). For the calculation a yearly turnover-rate
      of 33% with restocking from within the herd and a possibility of paratuberculosis
      diagnosis only in animals two years and older were assumed. The development of
      herd prevalence is exemplarily presented for four herds with different initial
      prevalences.

PMID- 11505847
TI  - [Perspectives of veterinary science--from the viewpoint of consumer health
      protection].
AB  - Concerning the causal chain "healthy animal--healthy food--healthy man" there's
      no doubt that mainly veterinarians are responsible for a safe preharvest area. In
      the food processing sector, of which economical importance is increasing in
      inverse proportion to agricultural activity of developed nations, the
      veterinarians must win through against many other professions. In this
      competition the specific veterinarian competence to prevent or to control
      microbiological, parasitological and some chemical hazards should be used.
      Therefore scientific work in veterinary public health has to concentrate on risk
      management. Additionally to developing methods for rapid and/or discriminative
      determination of causative agents the implementation of integrated quality
      assurance systems is needed in future according to the spirit of "intelligent"
      food hygiene.

PMID- 11505848
TI  - Computer simulation of costs and benefits of segregated early weaning (SEW) in a
      vertical pork production chain.
AB  - A simulation model was developed to quantify costs and benefits of segregated
      early weaning (SEW) compared to standard pork production in a vertically
      integrated system. The computer model considers the farrowing, fattening and
      slaughtering stage as well as the transportation of pigs between these stages.
      Input parameters relate to both biological and economic variables which were
      varied within a normal bandwith (sensitivity analysis, high and low level). Model
      output concerns the production costs per slaughter-pig in each stage and for the
      chain as a whole. With standard pork production the costs per head accounted for
      [symbol: see text] 131.72. 28% of the total chain production costs were raised by
      the farrowing stage, 15% by weaning-to-fattening period (28 kg live weight) and
      57% by the fattening stage (> 28 until 115 kg). Despite higher expenses for
      facilities, transportation and labour, SEW reduced the total chain production
      cost to [symbol: see text] 128.02 (low) and [symbol: see text] 121.32 (high) per
      head due to higher biological performance, lower medication and reduced fixed
      costs per unit. N- and P-excretion diminished by 13%. The results indicate that
      SEW may be an effective and beneficial alternative which meets some of the
      demands of pig producers and consumers such as effective production, good health
      and food safety.

PMID- 11505849
TI  - [A proposal for calculating the dustlike particle emissions from livestock
      buildings].
AB  - Particles emitted from livestock buildings are supposed to cause health
      implications in nearby residents. This increasingly causes conflicts between
      farmers and neighbours. At the same time the national emission control
      regulations are tightened and focus also on the environmental impact of
      particulate emissions. In front of this background a calculation model is
      presented by which the emitted masses of PM10 and PM2.5 from animal houses can be
      estimated. The model may help to establish emission inventories for particulates
      in rural areas with livestock production and can become a valuable instrument of
      the emission control act. The validity of the proposed model depends largely on
      the quality and amount of the input data. The more valid data are available the
      more precise the model can work. Therefore it will be necessary to improve the
      data sets on emission amounts for PM10 and PM2.5. In spite of these limitations
      it appears that a first and reliable estimation of particulate emission amounts
      from animal buildings can be given by the proposed model calculation.

PMID- 11505850
TI  - Non-bioequivalence of various trademarks of enrofloxacin and Baytril in cows.
AB  - Including Baytril, in various parts of the world many commercial preparations of
      enrofloxacin for parenteral administration are being employed for the treatment
      of bacterial diseases in cows. To optimize clinical responses and to minimize
      development of bacterial resistance to this agent, the copied pharmaceutical
      preparations must comply with some key pharmacokinetic features when
      bioequivalence studies are performed. To assess whether or not there was
      bioequivalence among nine commercial preparations of enrofloxacin and the
      original one, a controlled pharmacokinetic study was carried out. These was done
      utilizing the microbiological agar-diffusion test as quantitative/qualitative
      analytical method. A non-compartmental model defined kinetic variables. Results
      for Baytril revealed that maximal serum concentration (Csmax) was only matched by
      one preparation while area under the curve (AUC) of the serum
      concentration/activity of enrofloxacin and metabolites in time was not matched by
      any preparation. Time to Csmax (Tmax), elimination half-life, and shape of the
      time-serum concentrations of enrofloxacin profiles obtained for the nine generic
      preparations differ significantly somehow from the corresponding data obtained
      for the reference enrofloxacin. The need for studies to demonstrate
      bioequivalence becomes mandatory if similar preparations of enrofloxacin become
      commercially available. Enrofloxacin should be used selectively and cautiously to
      limit development of bacterial resistance. Non-bioequivalence of relevant
      pharmacokinetic values, such as Csmax and bioavailability (AUC) would facilitate
      development of bacterial resistance and limit the useful life span of this
      antibacterial agent.

PMID- 11505852
TI  - Combination BP therapy cuts second stroke risk in half.

PMID- 11505851
TI  - Alveolar rhabdomyosarcoma of the limb in a sheep.
AB  - Tumor mass was detected in the skeletal musculature of the tibia in a sheep
      slaughtered at abattoir. Histologically, the tumor cells were in a typical
      alveolar pattern, and showed a cartilaginous tissue differentiation in some areas
      of the tumor mass. This tumor examined by avidin-biotin-peroxidase method was
      found to be positive for myoglobin. The diagnosis of undifferentiated alveolar
      rhabdomyosarcoma was based on the results of histopathology and
      immunohistochemistry.

PMID- 11505853
TI  - Weight guidelines may be too restrictive for healthy patients over age 65.

PMID- 11505854
TI  - Low-dose HRT controls vasomotor symptoms with few side effects.

PMID- 11505855
TI  - Statin therapy may reduce risk of DVT in older persons.

PMID- 11505856
TI  - Red lesion on the hand. Irregular nodule grows quickly and bleeds easily when
      exposed to minor trauma.

PMID- 11505857
TI  - Parkinson's disease. Update in diagnosis and symptom management.
AB  - Parkinson's disease (PD) is a progressive neurodegenerative disorder with a high
      burden of morbidity. Because no diagnostic test exists for PD, clinical knowledge
      and skill are key to making an early, accurate diagnosis. Diagnostic criteria for
      PD require at least two of three motor signs: tremor, rigidity, or bradykinesia.
      Levodopa and the dopamine agonists are considered first-line drug therapy. Recent
      studies have shown a lower incidence of dyskinesia in patients who began therapy
      with a dopamine agonist, although levodopa may be better tolerated by patients
      age 70 or older. Combinations of medications and rehabilitative, alternative, and
      surgical therapies can often help patients achieve adequate control of PD motor
      symptoms and maintain a high quality of independent living.

PMID- 11505858
TI  - Avoiding hospitalizations for cellulitis.

PMID- 11505859
TI  - Functional assessment. Easy-to-use screening tools speed initial office work-up.
AB  - The mnemonic DEEP-IN stands for a series of easy-to-administer, office-based
      screening tests designed to streamline initial assessment of the geriatric
      patient. These screens can quickly identify signs of delirium, dementia,
      depression, and adverse drug effects; vision and hearing deficits; risk for
      future impairments in activities of daily living; incontinence, and malnutrition.
      The author developed the mnemonic from personal experience and from an evidence
      based application of validated geriatric and geropsychiatric studies.

PMID- 11505860
TI  - Alternative medicine. Achieving balance between herbal remedies and medical
      therapy.
AB  - The case patient was taking multiple herbal preparations as well as the
      prescription hypnotic zolpidem. The combination was probably increasing the
      patient's confusion, agitation, and aggression. The treatment team reached a
      compromise with the daughter after providing her with education and support. They
      continued the wheat germ oil and a multivitamin supplement, which appeared safe,
      even if of limited value. The patient continued taking valproate, 125 mg bid,
      which reduced her physical aggression and improved resistance to care. All other
      herbal remedies and zolpidem were discontinued. Balancing traditional therapies
      with requests for herbal remedies is a common challenge for physicians. The most
      successful intervention occurs when doctors familiarize themselves with herbal
      preparations and educate patients and families about the treatments.

PMID- 11505861
TI  - [Exercise tolerance tests in athletes, then what?].
AB  - Exercise tolerance tests in athletes are usually performed to evaluate aerobic
      exertion capacity and to plan training. They are based on simultaneous
      measurement of expired gases (determination of ventilation threshold and of
      VO2max). They can also be used to seek a possible cardiovascular anomaly,
      particularly in case of clinical symptoms or anomalies on auscultation; findings
      based on electrocardiography (rhythm, repolarisation, etc.) and on blood pressure
      readings, however, can lead to suspicion of an early anomaly and direct
      complementary investigation.

PMID- 11505862
TI  - [Systemic hypertension and sports practice. Epidemiology and therapeutics].
AB  - Hypertension, the most common cardiovascular disorder, also affects patients who
      want to practice a sport. Before counselling them, the physician should know the
      acute and chronic physiological effects of various sports. Is the activity
      authorised in a hypertensive? Yes, some physical activities are recommended and
      contribute to lower blood pressure readings. No, some other sporting activities
      can be dangerous and should be avoided. The choice of an antihypertensive agent
      should also take into account whether the hypertensive patient practices a sport,
      and especially if he/she participates in competitions.

PMID- 11505863
TI  - [Exertional hypertension and sport].
AB  - Defining the normal range of blood pressure during exertion is not easy. Each
      type of exercise induces increased blood pressure that responds to a particular
      curve, and adaptation modes differ according to age, gender, physical condition,
      basal blood pressure, etc. The best studied is blood pressure measured on the arm
      using a cycloergometre. Classical publications established blood pressure curves
      according to heart rate during exercise. It appears that the best scale of
      reference for power developed occurs in individuals who can provide a very high
      degree of effort and in particular, athletes who are in very good training.
      According to some authors, hypertension on exertion would entail a poor
      prognosis, even in the absence of resting hypertension. Nevertheless, there is
      presently no well established therapeutic recommendation concerning exertion
      hypertension. This approach could depend on resting blood pressure and on the
      existence of other risk factors. For an athlete, pursuing physical activity is
      most often encouraged, sometimes after treatment or adjustment of its level.

PMID- 11505864
TI  - [Sports and extreme conditions. Cardiovascular incidence in long term exertion
      and extreme temperatures (heat, cold)].
AB  - During ultra-endurance exercise, both increase in body temperature and
      dehydration due to sweat losses, lead to a decrease in central blood volume. The
      heart rate drift allows maintaining appropriate cardiac output, in order to
      satisfy both muscle perfusion and heat transfer requirements by increasing skin
      blood flow. The resulting dehydration can impair thermal regulation and increase
      the risks of serious accidents as heat stroke. Endurance events, lasting more
      than 8 hours, result in large sweat sodium chloride losses. Thus, ingestion of
      large amounts of water with poor salt intake can induce symptomatic hyponatremia
      (plasma sodium < 130 mEq/L) which is also a serious accident. Heat environment
      increases the thermal constraint and when the air humidity is high, evaporation
      of sweat is compromise. Thus, thermal stress becomes uncompensable which
      increases the risk of cardiovascular collapse. Cold exposure induces
      physiological responses to maintain internal temperature by both limiting thermal
      losses and increasing metabolic heat production. Cold can induce accidental
      hypothermia and local frost-bites; moreover, it increases the risk of arrhythmia
      during exercise. Some guidelines (cardiovascular fitness, water and electrolyte
      intakes, protective clothing) are given for each extreme condition.

PMID- 11505865
TI  - [Sudden death and physical activity and sports].
AB  - A growing number of people are involved in recreational physical activity. We
      examined the clinical and cardiac pathological patterns in 29 persons who died
      suddenly during a sport activity and were autopsied at the Institute of Forensic
      Medicine of Paris, 1990-1999. Twenty-seven males ranging in age from 13 to 57
      years, mean 30.5, and two females, 8 and 60 years old, died suddenly during a
      sport activity. The sports included running, 11 cases; cycling, 4; soccer, 3;
      swimming, 2; basket-ball, 2; rugby, 1, gymnastic exercises, 2; tennis, 1;
      gockart, 1; skiing, 1; hand-ball, 1 case. The causes of deaths were as follows;
      coronary artery disease, 9 cases; congenital anatomic anomaly of a coronary
      artery, 1; hypertrophic cardiomyopathy, 5; right ventricular dysplasia, 3;
      myocarditis, 2; endomyocardial fibrosis, 1; bridging of the left anterior
      descending coronary artery, 2; stroke, 2; rupture of aortic aneurysm, 4. Despite
      severity of lesions, only 4 victims had a known cardiovascular disease. Efforts
      should be continued to improve sensitivity and specificity of diagnostic tools
      and screening strategies. Therefore, medico-legal autopsies should be
      systematically performed for a better knowledge of sport-related mortality.

PMID- 11505866
TI  - [Lipid metabolism and exercise].
AB  - A high level of physical activity is associated with a lower cardiovascular risk
      in adult and elderly subjects. Several mechanisms are involved. Physical activity
      induces an increase in energy output. The contribution of fats to muscle energy
      metabolism increases with exercise duration. It decreases with exercise
      intensity. EPOC contributes by about 10% to the total energy cost of exercise.
      This supplementary energy expenditure is principally covered with fat oxidation,
      this being related to GH release. Part of energy expended during intermittent
      exercise is supplied by fat oxidation. The used lipids are taken from the
      muscular triacylglycerol stores and from the circulating FFA and lipoprotein
      triacylglycerols. Hydrolysis of triacylglycerols is achieved by LPL. Endurance
      training induces an increased contribution from fat to the exercise energy need.
      This results from increased muscle capillary density, enhanced activity of LPL
      and of the enzymes controlling beta-oxydation. The increased energy expenditure
      results in a reduced fat mass, which accounts for a decreased plasma
      triacylglycerol level. Endurance activity requiring approximately an expenditure
      of 60 kJ.kg-1 per week usually produces favourable lipoprotein changes. Level of
      post-prandial lipemia is lowered. These alterations disappear within the first
      two days of recovery.

PMID- 11505867
TI  - [Physiopathology of exercise-induced arrhythmias].
AB  - Physical exercise induces a big stress upon the cardiovascular system. It
      increases dramatically myocardial oxygen consumption. Thus, many different
      nervous, hormonal and ionic adaptations are requested to respond to physical
      exercise stress. These adaptations can induce or conversely stop cardiac
      arrhythmias.

PMID- 11505868
TI  - [Ventricular arrhythmia in the athlete: practical management].
AB  - The aim of athletic competition is to exceed ones present limits, which exposes
      the athlete to increased risk is helshe has a cardiac disorder. Ventricular
      excitability is not part of the athletic heart syndrome, and only the presence of
      resting ventricular extrasystoles that are monomorphic, ungrouped and disappear
      with exercise can be considered physiological. Significant ventricular arrhythmia
      can reflect a cardiac disorder that should be routinely sought in order to
      determine if there is a potential risk of sudden death favoured by physical
      effort. The confirmation of arrhythmia and seeking a cardiac disorder require a
      rigorous approach based on history-taking, clinical examination and initial
      performance of non-invasive, orienting examinations. Invasive examinations, based
      on the case, are often required if a disorder is suspected or if there is a
      question concerning the severity of the arrhythmia. Decisions concerning aptitude
      for competition are decided case by case, according to the disorder, with
      reference to the 26th Bethesda Conference. If the ventricular arrhythmia is shown
      to be benign and no underlying cardiac disorder exists, athletic competition may
      be pursued without restrictions. In case of contrary findings, physical activity
      will be limited and the authorized level will be precisely determined according
      to the context and the results of exertion tests made during treatment.

PMID- 11505869
TI  - [Heart and sports].

PMID- 11505870
TI  - [Hypertrophic cardiomyopathy and sports activities].
AB  - What advice should be given today to a patient with hypertrophic cardiomyopathy
      who wishes to participate in sports? The Bethesda recommendations of 1994
      strictly contraindicate competition in sports for any subject with hypertrophic
      cardiomyopathy, outside of a few activities with a very low level of energy
      expenditure. Nothing today suggests a change in these recommendations. Even if
      genetic knowledge of hypertrophic cardiomyopathy has progressed considerably, it
      is still not possible to determine precisely which forms are specific to a risk
      of sudden death linked to effort. Some forms of hypertrophic cardiomyopathy can
      be classified as high risk based on history-taking (familial antecedents of
      sudden death, syncope) and/or on genetic study, and/or on the results of
      complementary examinations (lack of blood pressure adaptation on exertion test,
      ventricular rhythm disorders, etc.) and in such cases extreme prudence should be
      recommended with regard to physical activity. On the other hand, if results
      indicate that the patient is at low risk, limited, submaximal physical activity
      can be envisioned, taking into account the results of the exertion test and
      Holter readings made during physical activity. Periodic re-evaluation of
      tolerance to exertion is then indispensable.

PMID- 11505871
TI  - [Electrocardiographic features of the athlete: what are the limits?].
AB  - The athlete's heart syndrome concerns only high level trained subjects. The
      classical electrocardiographic features of this syndrome are hypokinetic
      arrhythmia as bradycardia, low level of atrioventricular and of right bundle
      branch block and electrocardiographic T wave alterations. Sometimes, marked
      ventricular repolarisation alterations can suggest the presence of heart disease.
      These electrocardiographic patterns seem linked to the alterations of the two
      drive of autonomic nervous system (sympathetic and parasympathetic) and to
      cardiac hypertrophy. In all cases, it must be kept in mind that the athlete must
      be free of clinical symptoms and that these electrocardiographic alterations must
      disappear during exercise and in case of physical training cessation. In case of
      doubt a cardiologist judgement must be performed.

PMID- 11505872
TI  - The need to develop additional rapid HIV tests in the U.S.

PMID- 11505873
TI  - Molecular principles underlying hepatitis C virus diagnosis.
AB  - Although the rate of new cases of HCV infection has decreased as a result of
      public health policies related to intravenous drug users, the overall rate of
      infection in the U.S. is still high. With an estimated 3.9 million people
      infected nationwide, combined with the observation that, for over 50% of all
      cases of HCV infection, a route of infection is unknown, HCV will continue to be
      a major cause of infectious disease related morbidity and mortality for years to
      come. The benefit of molecular assays resides in providing for more effective
      treatment of HCV-infected patients, which will certainly justify the expense.

PMID- 11505874
TI  - The use of phosphorylation state specific antibodies (PSSAs) to study cell cycle
      regulators.

PMID- 11505875
TI  - Lp(a) concentration in moderate renal insufficiency.

PMID- 11505876
TI  - The importance of heterogeneous detection as troponin becomes the standard in the
      diagnosis of myocardial infarction.

PMID- 11505877
TI  - Next-generation applications for laser-based tools in biotechnology.

PMID- 11505878
TI  - An immune-based assay for HIV disease management.
AB  - Today, patients infected with HIV are monitored routinely for their levels of
      CD4+ T cells and viral load. Since either or both of these parameters are often
      discordant with the clinical course, the direct measurement of immune function to
      more accurately reflect clinical status is needed (Figure 3). The in vitro CMI
      test provides a rapid method for assessing cell-mediated immunity and is an
      important adjunct to the clinical management of these patients.

PMID- 11505879
TI  - Proteins and antibodies make advances as therapeutic products.

PMID- 11505880
TI  - Effectiveness of high dose dexamethasone in the treatment of acute stroke.
AB  - A prospective double-blind placebo-controlled, randomised clinical trial was
      carried out to determine the effectiveness of short-course of high dose
      dexamethasone therapy on mortality and neurological recovery in stroke patients.
      During a sixteen month period of study, 230 patients with clinical diagnosis of
      stroke were seen. Of these, 40 were eligible for the study (27 were presumed to
      have had haemorrhagic stroke; and 13 were presumed to have had cerebral
      infarction). The commonest cause of exclusion was presentation after 24 hours of
      the ictus. Patients were sequentially paired and randomised into high dose
      dexamethasone and placebo groups in a double-blind fashion. There were twenty
      patients in either group. Of the 27 patients with haemorrhagic stroke, 15 were in
      the dexamethasone group and 12 in the placebo group. Of the 13 patients with
      cerebral infarction, 5 were in the dexamethasone group and 8 in the placebo
      group. Each patient received 100 mg of dexamethasone stat, and 16 mg every 6
      hours for a period of 48 hours or equivalent volumes of placebo. Assessment of
      each patient was done using a neurological score. Sequential analysis by Armitage
      was employed, using survival at 1 month as the primary criterion of
      effectiveness. Survivors were followed-up for 6 months. At the end of one month,
      16 patients (80%) had died in the dexamethasone group and 17 (85%) in the placebo
      group. The average day of death was six days in the dexamethasone group and 15
      days in the placebo group, but this was not statistically significant. Of the
      seven survivors at one month, four were in the dexamethasone group and 3 in the
      placebo group. Five of them had cerebral infarction and two had haemorrhagic
      stroke. The two in the haemorrhagic subgroup who survived the first month died at
      the 2nd and 4th month respectively. At the end of six months, only the five
      patients with cerebral infarction were alive. Of these, 2 in the dexamethasone
      group were back at work while the third was chair-bound. The 2 survivors in the
      placebo group were chair and bed bound respectively. In conclusion, this study
      failed to demonstrate any benefit of a short-course of high dose steroid in
      improving the mortality of stroke patients and its use should be discouraged.
      However, possible benefit in the morbidity of survivors in the patients with
      cerebral infarction requires further studies.

PMID- 11505881
TI  - Levels of calcium, aluminium and chromium in serum of exclusively breastfed
      infants at six months of age in Savannah region of Nigeria.
AB  - This study was undertaken to determine the levels of calcium, aluminium and
      chromium in the serum of apparently healthy exclusively breastfed infants at the
      sixth month of lactation. Forty-five infants (with a male:female ratio 2:1) were
      studied. They were of an average age six months and one week, weighed 6.8-10.0
      kg. The mean calcium levels of 83.92 ug/ml (2.1 mmol/L) obtained is within the
      reference range (2.1-2.5 mmol/L) in this area. The mean level of chromium was
      0.11 u/ml while that of aluminium is significantly (P < 0.001) higher than the
      toxic level reported by some workers, yet none of the subject was manifesting any
      obvious signs of toxicity. We can then infer from our data that the exclusively
      breastfed infants are able to extract enough calcium, aluminium and chromium from
      the maternal breastmilk.

PMID- 11505882
TI  - Nucleolar organizer regions in jaw tumours of cartilaginous origin.
AB  - Nucleolar organizer regions [NORs] are loops of DNA that transcribe to ribosomal
      RNA. They can be visualized as intranuclear black dots by histochemical staining
      with a colloid silver solution. Silver-stained nucleolar proteins [AgNORs] were
      counted in cases comprising of primary chondrosarcomas of three histologic
      grades, in chondromyxoid fibroma and in controls comprising of normal bone and
      cartilage tissues of the jaw bones. The AgNOR counts increased step-wisely from
      normal bone tissue [1.11 0.4], chondromyxoid fibroma [2.66 0.78], grade I
      chondrosarcoma [3.94 0.34], grade II chondrosarcoma [4.32 0.52], and grade III
      chondrosarcoma [5.54 0.44]. There was a statistically significant difference in
      the mean AgNOR counts between grade 1 and grade III chondrosarcoma [p < 0.05].
      The mean AgNOR counts for benign cartilaginous [chondromyxoid fibroma] tumour was
      significantly lower than the mean, AgNOR count for malignant cartilaginous
      tumours [chondrosarcomas] [p < 0.05]. The results in the present study indicate
      that silver colloid staining is a useful technique for evaluating the
      proliferative activity of chondrosarcoma and benign cartilaginous tumour such as
      chondromyxoid fibroma.

PMID- 11505883
TI  - Tuberculosis masquerading as 'constant malaria'.
AB  - Four hundred adults aged 20-60 years, (200 females and 200 males) were studied.
      All the subjects were residing in the urban areas of Lagos, Nigeria. Thirteen
      percent claimed they were having "constant malaria" (> 8 times per year), 5% (20)
      claimed to have cough mostly during the cold period, 2.5% (10) produced mucoid
      sputum, 2.5% unproductive cough, 13% were AFB smear positive, 1.5% had positive
      chest X-ray for pulmonary Tuberculosis (PTB), 1.5% were HIV positive and 50% were
      mantoux positive (> 10 mm induration). All who complained of "constant malaria"
      were AFB positive. Malaria parasite density was lower in those who complained of
      "constant malaria" than those who did not complain (P = 0.003). The complaint of
      frequent malaria attack decreased after Antituberculosis therapy for 6 months.
      This study revealed that in a malaria and tuberculosis endemic region, early
      stage of tuberculosis can masquerade as "constant malaria". Therefore any such
      complaint should be fully investigated.

PMID- 11505884
TI  - 5-yearly monitoring of trends of substance use among secondary school students in
      Ilorin, Nigeria, 1988-1998.
AB  - This report describes the trends of substance use among youths by comparing data
      collected among senior secondary school students in Ilorin metropolis, Kwara
      State, Nigeria at 5-yearly intervals (1988-1998). In 1998, data were collected
      from 750 senior secondary school students from six secondary schools in the study
      area using a self-report 117-item questionnaire based on the World Health
      Organization (WHO) guidelines for student substance-use surveys. Substances
      investigated in the survey were alcohol, cigarettes, cannabis, strong and mild
      stimulants, hypnosedatives, antibiotics, cocaine, heroin, organic solvents and
      hallucinogens. These data were compared with similar ones collected from students
      with similar characteristics, and from the same six schools in 1988 and 1993. It
      was found that high use substances were mild stimulants, antibiotics and alcohol,
      while cigarettes, cannabis, heroin and cocaine remained low-use substances. Most
      current users of all the substances were occasional users, except for cigarettes
      and cannabis where more frequent (daily and weekly) usage was reported. There was
      also a significant increase in the use of alcohol, organic solvents, mild
      stimulants and hypnosedatives, and a significant reduction in cigarette smoking
      over the three data waves. No gender difference was recorded for alcohol,
      hypnosedatives and cocaine use in the three data waves. It was concluded that
      although some substances recorded significant increases in their usage over the
      three data waves, the current use rates were still generally low and comparable
      to those of other Nigerian studies. Substances used were those employed mainly
      for study purposes (mild stimulants and hypnosedatives), and most students used
      the substances only on occasional basis. Nonetheless, in view of the rapidly
      changing socio-economic life of Ilorin City, it has become imperative to continue
      with the 5-yearly monitoring of trends.

PMID- 11505885
TI  - Curvilinear formulae for predicting peak expiratory flow rate in adult Nigerians.
AB  - Predicted values of Peak expiratory flow rate (PEF) using linear formulae do not
      closely agree with observed trends. Predicted values tend to be higher than
      observed values among youths and the elderly while they are usually lower than
      observed values among people within the prime of life. All prediction formulae in
      Nigeria are linear. In this study, more fitting curvilinear formulae were derived
      for male and female subjects from PEF values obtained from a study of 1009
      subjects made up of 668 males and 341 females between the ages of 15 and 82 years
      living and/or working in Port Harcourt, Nigeria and its environs. We hope that
      these formulae may be put to greater use since they agree more closely with the
      observed trends.

PMID- 11505886
TI  - Serum ferritin and other haematological measurements in apparently healthy
      children with malaria parasitaemia in Lagos, Nigeria.
AB  - One hundred apparently normal nursery and primary school children aged between 2
      to 12 years from private schools, in Lagos Nigeria were studied. From this study
      the mean ferritin levels for children aged 2-5 years, and 6-12 years were 112 +/-
      48 micrograms/l, and 119 +/- 38 micrograms/l respectively. Mean haematocrit
      values were 37.6 +/- 2.2%, and 37.5 +/- 2.6%, while mean haemoglobin levels were
      126 +/- 9 g/l 127 +/- 7.9 g/l (2-5 years and 6-12 years respectively). The mean
      values for MCV, MCH, MCHC were 92 +/- 8.6 fl, 27.6 +/- 3.0 pg, 338.0 +/- 15.0 g/l
      and 93.5 +/- 9.0 fl, 28.7 +/- 2.5 pg, 332.0 +/- 17.0 g/l (2-5 years and 6-12
      years respectively). All haematological parameters measured were similar in both
      malaria parasitaemia positive and negative subjects, except ferritin level which
      was significantly higher in subjects with malaria parasitaemia (p < 0.05). There
      was positive correlation between ferritin concentration and malaria density (r =
      0.85, p < 0.05). From the above findings, it would be concluded that, ferritin
      estimation without examination for malaria parasitaemia in a malarious region
      like Nigeria is not reliable. It is also concluded that with the high mean
      ferritin level obtained in this study for normal children on balanced diet,
      routine iron supplementation may not be necessary for this group of children in
      Nigeria.

PMID- 11505887
TI  - Angiotensin converting enzyme inhibitor induced cough in Nigerians.
AB  - A persistent dry cough is the commonest class of adverse reaction to Angiotensin
      converting enzyme inhibitors (ACE-I). This ACE-I induced cough appears to exhibit
      interracial differences being commoner in Chinese subjects as compared to
      Caucasians. We conducted a cross sectional study of one hundred (100) patients
      (63 males and 37 females) on ACE-I to determine the prevalence of ACE-induced
      cough in Nigerians, a Negroid population. Twenty seven patients (27%) had ACE
      induced cough and four (4%) had withdrawal of ACE-I therapy on account of cough.
      The prevalence of ACE-I induced cough was significantly higher amongst females
      (43%) as compared to males (17%) p < 0.01. The biological basis for the apparent
      racial and gender differences in ACE-I induced cough requires further study.

PMID- 11505888
TI  - A five year review of splenic injuries in the University of Benin Teaching
      Hospital, Benin City, Nigeria.
AB  - Splenic injuries are common and require emergency treatment. Efforts are now
      geared towards splenic conservation by way of splenorrhaphy. Thirty cases of
      splenic injuries seen at the University of Benin Teaching Hospital, Benin City,
      Nigeria between June 1992 and June 1997 were evaluated with a view to assessing
      the pattern of injuries and the management with respect particularly to splenic
      conservation. Males accounted for 66.6% of cases and the age range was 3-57 years
      (mean 20.8). Road traffic accident was the leading cause (63.3%) of injury.
      Splenic injuries were graded in severity from grades one to five based on the
      organ injury scaling. Injuries in 3(10%) cases were Grade 1, 5(17%) Grade 2,
      7(23%) Grade 3, 4(20%) Grade 4 and 9(30%) Grade 5. Because majority of the
      splenic injuries were severe only four (13.3%) in Grades 1 and 2 had salvage
      operation of splenorrhaphy. All the other patients had splenectomy. Splenic
      conservation has been little practiced but could be encouraged by the more
      experienced surgeons having more interest in preserving splenic functions.

PMID- 11505889
TI  - Paediatric surgery in the rural setting: prospect and feasibility.
AB  - This report is based on a 6-year experience with surgery in children in a rural
      hospital in Northern Nigeria. Paediatric surgery represents 6.6% of all
      paediatric work-load and 9.6% of all operative surgery. Majority of the
      operations were performed for congenital problems (40%) and less frequently
      infections (22%) and trauma (21%). Most of the infective and trauma problems were
      preventable. The mortality was 7.3%, due mostly to septic complications. Overall,
      95% of the operations were not of complex nature and could be performed by
      general duty doctors with general surgical experience. These doctors who are more
      readily available in rural areas should be encouraged to perform these operations
      to reduce the economic and emotional burden on rural families. However, the more
      complex congenital conditions should always be referred early to specialist
      hospitals. Surgical conditions cause significant morbidity and mortality in
      children and should not be overlooked in the planning of child health care
      services in rural areas.

PMID- 11505890
TI  - A follow up report: recurrent Cushing's syndrome after bilateral adrenalectomy.
AB  - This is a case report of a 23 year old female. She had earlier been diagnosed to
      have Cushing's syndrome due to macronodular adrenal hyperplasia, for which
      bilateral adrenalectomy was performed three years before. The initial full
      recovery was sustained for about one and a half years, following which there was
      progressive recurrence of obesity, hypertension and hypercalcaemia. Plasma
      cortisol concentrations were markedly elevated and a diagnosis of recurrent
      Cushing's syndrome was made. Pre-operative localisation of the source of
      hypercortisolism through intravenous urogram, abdominal ultrasonogram and
      computerised tomogram was unfruitful, thus an exploratory laparatomy was
      undertaken. At surgery, extensive and dense adhesions were seen which caused
      difficult dissection and accidental injury to the patient's liver and kidney,
      necessitating massive intra-operative blood transfusions. The patient died within
      two hours of recovery from anaesthesia of acute massive pulmonary embolism. We
      postulate that the recurrent Cushing's syndrome in this patient could have been
      due autografting of remnants of adrenal tissue within the abdominal cavity. A pre
      operative localisation with radio-labelled cholesterol scanning may have made
      reoperation of the patient easier.

PMID- 11505891
TI  - Amelogenesis imperfecta: a case report.
AB  - A case of amelogenesis imperfecta in a Nigerian is presented. Although the
      patient had almost full complement of teeth, their structure was physically weak
      and many of them were discoloured. Many of the teeth had lost their enamel and
      worn down rapidly causing great sensitivity, pain and aesthetic problems for the
      patient. The clinical features and management of this case are discussed.

PMID- 11505892
TI  - Brain cardiac events in Nigerian patients with cocaine abuse.
AB  - Epidemiological evidences indicated that substance abuse disorders are
      increasingly prevalent among Nigerians. The psychosocial deleterious effects of
      these drugs appear well recognised, but their medical consequences are less often
      considered in the region. The potential for these drugs to precipitate life
      threatening cardiac and brain event needs to be reemphasised. We report the
      clinical and laboratory findings in 4 Nigerians in whom non-intravenous use
      (recreational and ritualistic) of cocaine was temporally related to acute
      myocardial ischaemia, cardiac dysarrhythmias, convulsion and cerebrovascular
      accident. These findings suggest that the observations--that underlying heart
      disorders were not sinequanon for the cardiotoxic effects of cocaine; the brain
      and cardiac consequences were not restricted to parenteral use of the drug; the
      development of seizures were not prerequisite for cerebrovascular accident and
      vice versa; and that massive doses of the drug needed not be ingested to produce
      toxic effects on the heart and brain--may also apply in these Nigerian patients.
      Perhaps with the increase in user population, it is timely to embark on public
      enlightenment on the medical dangers of cocaine abuse, as these are no less
      important than the psychosocial consequences.

PMID- 11505893
TI  - Grey-scale and Doppler ultrasound of normal testes and extratesticular structures
      -a pictorial review.
AB  - Recent advances in ultrasound technology has led to the development of high
      resolution transducers, typically 7 to 10 MHZ, with grey-scale, pulsed wave
      duplex Doppler, colour Doppler and even power Doppler capabilities. Computed
      tomography, scintigraphy and magnetic resonance may be used to image the testis,
      but ultrasound is the most sensitive imaging modality available for demonstration
      of scrotal contents. Ultrasound has the additional advantages that it is
      relatively cheap and widely available, and does not involve the use of ionizing
      radiation. Real time grey-scale ultrasound provides good cross-sectional images,
      whilst pulsed Doppler and colour Doppler ultrasound provide quantitative and
      directional information on vascular flow within the testis. We have presented a
      pictorial review of normal findings encountered in sonographic imaging of several
      testes, as well as anatomical variants, and emphasized the importance of their
      recognition using various ultrasound techniques. We have also briefly reviewed
      ways of optimizing the images obtained from ultrasound scanners.

PMID- 11505894
TI  - Acute calcific tendinitis simulating tendon sheath infection.
AB  - Tendon sheath infection has catastrophic consequences if not diagnosed. We
      present acute calcific tendinitis, a simulator of tendon sheath infection with a
      good prognosis in a 14 year old athletic tennis player.

PMID- 11505895
TI  - Ogilvie's syndrome (colonic pseudo-obstruction) occurring in an 18-year-old
      Nigerian female.
AB  - Ogilvie's syndrome which is colonic obstruction without an identifiable distal
      mechanical cause is reported in an 18 year old female Nigerian. A high index of
      awareness is required to diagnose this condition.

PMID- 11505896
TI  - Acute (haematogenous) osteomyelitis of the skull in childhood.
AB  - A 13-year old boy presented with a 2-week history of right frontotemporal
      headache, fever and progressive painful swelling in that region. There was no
      preceding trauma. Clinical and radiological evaluation confirmed osteomyelitis of
      the right frontal bone. Staphylococcus aureus was found to be the causative
      organism. The affected bone was debrided and appropriate antibiotics
      administered. A subdural abscess developed requiring drainage. Hospital stay was
      8 weeks. Haematogenous (pyogenic) osteomyelitis of the skull is rare in childhood
      and diagnosis may be missed or delayed. A high index of suspicion is necessary to
      make an early diagnosis and to avoid morbidity and mortality.

PMID- 11505897
TI  - Long-range transport in the environment.

PMID- 11505898
TI  - The spatial scale of organic chemicals in multimedia fate modeling. Recent
      developments and significance for chemical assessment.
AB  - In the last years, the spatial range (SR) or characteristic travel distance (CTD)
      of organic chemicals has found increasing scientific interest as an indicator of
      the long-range transport (LRT) potential and, in combination with persistence, as
      a kind of 'hazard' indicator on the exposure level. This development coincides
      with European debates about more effective and more preventive approaches to the
      chemicals assessment, and about an international, legally-binding instrument for
      the phase out of persistent organic pollutants (POPs). Persistence and LRT
      potential are important issues in these debates. Here, the development of the
      concept of assessing the spatial scale from early ideas in the 1970s and 1980s to
      recent studies in the field of multimedia fate and transport modeling is
      summarized. Different approaches to the modeling of environmental transport
      (advective and dispersive) and different methods for quantifying the SR or CTD
      are compared. Relationships between SR or CTD and different persistence measures
      are analyzed. Comparison of these relationships shows that conclusions for
      chemical assessment should be based on an evaluation of different persistence and
      spatial scale measures. The use of SR or CTD and persistence as hazard indicators
      in the chemicals assessment is illustrated.

PMID- 11505899
TI  - BETR North America: a regionally segmented multimedia contaminant fate model for
      North America.
AB  - We present the Berkeley-Trent North American contaminant fate model (BETR North
      America), a regionally segmented multimedia contaminant fate model based on the
      fugacity concept. The model is built on a framework that links contaminant fate
      models of individual regions, and is generally applicable to large, spatially
      heterogeneous areas. The North American environment is modeled as 24 ecological
      regions, within each region contaminant fate is described using a 7 compartment
      multimedia fugacity model including a vertically segmented atmosphere,
      freshwater, freshwater sediment, soil, coastal water and vegetation compartments.
      Inter-regional transport of contaminants in the atmosphere, freshwater and
      coastal water is described using a database of hydrological and meteorological
      data compiled with Geographical Information Systems (GIS) techniques. Steady
      state and dynamic solutions to the 168 mass balance equations that make up the
      linked model for North America are discussed, and an illustrative case study of
      toxaphene transport from the southern United States to the Great Lakes Basin is
      presented. Regionally segmented models such as BETR North America can provide a
      critical link between evaluative models of long-range transport potential and
      contaminant concentrations observed in remote regions. The continent-scale mass
      balance calculated by the model provides a sound basis for evaluating long-range
      transport potential of organic pollutants, and formulation of continent-scale
      management and regulatory strategies for chemicals.

PMID- 11505900
TI  - Development of continental scale multimedia contaminant fate models: integrating
      GIS.
AB  - The incentives and approaches for modelling chemical fate at a continental scale
      are discussed and reviewed. It is suggested that a multi-media model consisting
      of some 20-30 regions, each of which contains typically seven environmental
      compartments represents a reasonable compromise between the issues of the need
      for detailed resolution, avoidance of excessive data demands and inherent
      complexity and transparency. Strategies adopted in compiling the Berkley-Trent
      (BETR) model for North America are discussed and used to illustrate the issues of
      selecting appropriate number and nature of segments, treatment of air and water
      flows and the acquisition of environmental data. It is suggested that GIS
      software can play a valuable role in gathering and processing such data and in
      the display and interpretation of the results of the model assessment. The BETR
      model will be a useful tool for describing the nature of persistence and long
      range transport of chemicals of concern in the North American environment.

PMID- 11505901
TI  - Long-range transport potential of semivolatile organic chemicals in coupled air
      water systems.
AB  - Ongoing deliberations on the regulation of semivolatile organic chemicals require
      the assessment of chemical transport in atmospheric and marine systems. The
      characteristic travel distance was proposed as a measure for the transport
      potential in air and water. However, the existing definition treats the transport
      processes separately. It is shown that combined transport in coupled air-ocean
      systems can accelerate the overall transport into remote regions. Concentration
      ratios in air and water change with distance from sources depending on the
      initial concentration ratio and on the difference between the transport
      velocities. A measure is suggested facilitating the chemical screening with
      respect to transport potentials in such air-ocean systems. A case study for alpha
      and gamma-hexachlorocyclohexane shows that the suggested measure qualitatively
      reveals the transport potentials of these chemicals and exemplifies possible
      concentration patterns.

PMID- 11505902
TI  - A multi media load model for the Baltic Sea.
AB  - The background of this work is the international decision process with regard to
      the selection of chemicals to be assessed with priority. In order to stress the
      precautionary principle, mass flows were analysed rather than concentrations,
      threshold values, etc., as preferred by the chemical legislation (which still
      excludes the marine area). Lindane, hexachlorobenzene (HCB), trichloroacetic acid
      and its sodium salt, medium-chained chlorinated paraffins and tributyltin (TBT)
      were selected due to their great relevance for the marine area. Trichloroacetic
      acid is an interesting model compound on account of its accidental formation by
      degradation of volatile chlorinated hydrocarbons and during chlorination
      processes. In addition, a hypothetical compound was modelled, representing a
      highly water-soluble substance with low vapour pressure. The balancing area is
      the Baltic Sea and its catchment area. In order to model the substance flows, the
      'Input/Output-load model' has been developed. The model quantifies the shift and
      the distribution of a yearly load of the substance investigated from the
      terrestrial-limnic into the marine compartment (Baltic Sea). Water-soluble
      substances, which are usually considered to be of no concern, may enter the sea
      in great amounts and, if not degradable, remain there. It turned out to be
      necessary to take into account remobilisation, unintended formation and point as
      well as line-sources.

PMID- 11505903
TI  - The significance of PCBs in the atmosphere of the southern hemisphere.
AB  - Air monitoring stations were set up at 2 sites in the southern hemisphere--Moody
      Brook, Falkland Island (51 degrees 25' S, 57 degrees 56' W) and Halley, Research
      Station, Antarctica (75 degrees 35' S, 26 degrees 30' W). PCBs were monitored at
      the stations throughout 1999. Highest concentrations were observed when
      temperatures were greater. In general, concentrations were greater at Moody Brook
      than at Halley, although the difference in concentrations between sites was less
      for more chlorinated congeners. Air concentrations at both sites were compared
      with samples collected nearby over-water. Over water air concentrations were
      found to be greater than over land air concentrations. Concentrations were also
      compared with literature data for air concentrations at a remote site in the
      Canadian Arctic. Atmospheric concentrations of tri-chlorinated biphenyls were
      found to be approximately double those reported for Ellesmere Island in the
      Canadian Arctic, whilst concentrations in samples from Antarctica were very
      similar to those found in the high Arctic. Most other PCBs were a factor of 2-4
      greater in the Canadian Arctic.

PMID- 11505904
TI  - Photodegradation of halobenzenes in water ice.
AB  - Results from the photolysis of o, p-dichlorobenzene, bromobenzene, and p
      dibromobenzene in water ice are reported. All phototransformations appeared to be
      based on dehalogenation, coupling, and rearrangement reactions in ice cavities.
      No photosolvolysis products, i.e. products from intermolecular reactions between
      organic and water molecules, were found. Many of the products were very toxic
      substances of a high environmental risk, such as PCBs. The results support our
      model, in which secondary, very toxic, pollutants can be formed in ice, snow, and
      atmospheric ice particles from primary pollutants through the action of solar
      irradiation. The photoproducts may be released to the environment by ice melting
      and evaporation.

PMID- 11505905
TI  - Regional background monitoring of PBT compounds. The comparison of the results
      from measurements and modelling.
AB  - A comparison of the modelling results of persistent, bioaccumulative and toxic
      (PBT) chemicals is presented with measurements. Contribution will present mean
      annual concentrations calculated and observed at EMEP stations and their ratios.
      The comparison of the calculated results with older results indicates that the
      model modification improved the agreement with measurement data. PBT compounds in
      ambient air are monitored in the area of Kosetice observatory (professional
      observatory of the Czech Hydrometeorological Institute located in south Bohemia).
      Calculated and measured mean annual concentrations of PBTs in precipitation,
      soil, vegetation and their ratios are presented. It should be mentioned that the
      number of measurements in such compartments as seawater, soil and vegetation is
      insufficient for model verification at present. The agreement between results
      from MSC-East models and results from long-term regional air background
      monitoring in Central Europe is good.

PMID- 11505906
TI  - The elaboration of the 'Stockholm convention' on persistent organic pollutants
      (POPs): a negotiation process fraught with obstacles and opportunities.
AB  - The conclusion in December 2000 of the negotiations for the 'Stockholm
      Convention' can clearly be labeled as a success. The Convention text was
      negotiated in merely five sessions of the Intergovernmental Negotiating Committee
      (INC) and accomplished after its fifth session despite the fact that numerous
      controversial issues, such as the inclusion of new substances under the ambit of
      the Convention, the acknowledgement of the precautionary principle or--clearly
      most controversial--the financing mechanisms, remained to be resolved. This paper
      attempts to provide a somewhat impressionistic account of the negotiations
      leading to the conclusion of the 'Stockholm Convention' as experienced by the
      members of the Swiss delegation participating in the negotiations of the INC.
      Besides a brief overview on the 'history' of the negotiations, it will focus on
      some issues of special interest--and controversy--to the negotiators, and finally
      attempt to provide an outlook on the future of the work performed by the INC and
      the implementation of the Convention. Issues of special interest are
      environmental policy issues, capacity building and financing, trade-related
      issues, precautionary principles, and technical and scientific issues.

PMID- 11505907
TI  - Environmental risks of chemicals and genetically modified organisms: a
      comparison. Part II: Sustainability and precaution in risk assessment and risk
      management.
AB  - The principles of precaution and sustainability require more consideration in the
      assessment of environmental risks posed by chemicals and genetically modified
      organisms. Instead of applying risk reduction measures when there are serious
      indications for damage, full scientific certainty is often waited for before
      taking action. The precautionary principle particularly should be applied in
      those cases in which the extent and probability of damage are uncertain, e.g. in
      the case of persistent chemicals which are additionally bioaccumulative or highly
      mobile. Based on these principles, environmental action targets for risks
      associated with GMOs and chemicals can be developed. Risk management not only
      includes statutory measures but also instruments designed to influence behaviour
      indirectly are important to achieve the goals. Particularly for risks of GMOs
      which provoke fear, risk communication is important. Some rules to which
      attention should be paid in communication with the public are presented.

PMID- 11505908
TI  - [Anxious-phobic disorders in patients with dyspnea].
AB  - The examination included 35 patients (21 women, 14 men, mean age 47.2 +/- 2.4
      years) with anxious-phobic disorders (APD) and dyspnea phenomena combined
      bronchial asthma (BA) and hyperventilation syndrome (HVS). There was established
      that APD in these cases develops more frequently similarly to the panic attacks
      (PA) and HVS was PA component. Three PA types with dyspnea phenomena were
      recognized: cognitive ones (with prevalence of cognitive anxiety--8 cases);
      somatized PA (with prevalence of somatized anxiety--18 cases) and PA with both
      cognitive and somatized anxiety (9 cases). PA of the first type amplifies BA
      attack (psychopathologic structure of PA was integrated with manifestations of
      the acute bronchial obstruction). PA of the second type duplicates (because of
      the pronounced somatized anxiety associated with asphyxia) an acute bronchial
      obstruction between BA paroxysms. PA of the third type imitates somatic pathology
      forming without its participation (polymorphic conversion disorders were found
      first of all). The link of severity of the anxious-phobic and pulmonary pathology
      can be interpreted in the ranges of psychosomatic conception of the "reciprocal
      correlations".

PMID- 11505909
TI  - [Dependence of the formation of the addictive personality on the predisposing
      factors].
AB  - During observation of 100 patients with consequences of different types of drug
      addictions (heroin, opium, poly-drug, pervitine-ephedrine) a complex of social
      and biological factors was analyzed: heredity, premorbid personality, somatic
      diseases, nurture, age of the onset of drug-addiction, duration of drug abuse, a
      social behavior. Influence of these factors was studied according to the
      following parameters: alteration of personality; degree of the moral-ethic
      decline and of the intellectual-mnestic disorders; somatic complications; the
      presence of the suicidal trends; frequency of self-damages; a professional level;
      family interrelations; frequency of the delinquencies (including conviction). On
      the basis of the correlation analysis it was established that the most
      significant unfavorable prognostic factors, which had determined a rate of the
      formation of the addictive personality were the following (in order of the
      decrease of significance): perinatal pathology; family history of alcoholism,
      drug-addiction and other mental diseases; personality deviations in premorbid
      period; an early age of the onset of drug addiction; a type of the drug;
      education; alcoholic abuse before the addiction; duration of the addiction.

PMID- 11505910
TI  - [Electric stimulation of the brain in patients with hepatocerebral Wilson
      Konovalov's degeneration (neuromorphological and neurophysiological analysis)].
AB  - 36 stereotactic operations were carried out in 27 patients. Either the total lack
      of hyperkinesis or its significant decrease was found in 17 cases; 5 patients
      died. There was no correlation between manifestations of hepatocerebral
      degeneration and relatively normal quantitative characteristics of both cortical
      and subcortical biopotentials. These potentials are produced on the background of
      the microstructural changes in the neurons of the same regions. It is suggested
      that qualitative importance of such biopotentials lies in their exceeding
      pathologic impulsation, arising hyperkinesis. That was confirmed by the fact,
      that hyperkinesis eliminates after surgical destruction of the ventrolateral
      nucleus of the thalamus and the subthalamic structures.

PMID- 11505911
TI  - [Change of bioelectric brain activity registered at the distance from the focus
      of cerebral tissue injury].
AB  - The focal delta-waves and the remote influences of the stroke in the form of the
      sinusoidal flashes of delta-waves with a maximal amplitude exceeding an amplitude
      of the focal delta-waves (frontal flashes--FF) in frontal-polar leads were
      investigated in 51 patients (22 men, 29 women) by means of mapping, dipole
      location (BrainLoc) and LORETA methods. The patients were examined in dynamics
      during the acute period of hemispheric stroke on days 1-3, 14 and 21 after the
      onset of the disease. The usage of the modern computer methods of EEG analysis
      permits to consider FF as an independent electrophysiological phenomenon and to
      localize a zone of the sources of such flashes, which does not coincide with the
      zone of generation of the focal delta-activity that corresponds to the perifocal
      zone of the stroke. According to the data of the three-dimensional location a
      probable zone of FF generation corresponds to the frontal pole and medial-basal
      areas of the frontal lobe. Comparison with the MRI data leads to the conclusion
      that a damage of anterior white substance was the most frequent cause of FF
      development, probably by deafferentation mechanism. FF may be an
      electrophysiological manifestation of the influence of the damage of the
      different brain structures on the frontal lobes according to diaschisis
      mechanism.

PMID- 11505912
TI  - [EEG peculiarities in posttraumatic Korsakov's syndrome].
AB  - The paper presents an attempt to define the structures of the cerebral functional
      pathologic system in the Korsakov's syndrome (KS) that develops after a severe
      craniocerebral trauma. 32 patients with reversible (21) and irreversible (11) KS
      variations were examined. Visual and coherent EEG-analysis was performed as well
      as determination of the three-dimensional location of the equivalent dipole
      sources of the separate pathologic components of the bioelectric activity. The
      data obtained were compared with the clinical ones. The role of both diencephalic
      and subcortical (including hippocampus) structures in KS development as well as
      the role of the right hemisphere were confirmed. Significance of the anterior
      (temporal-frontal-central) regions of the right hemisphere in KS regression was
      found. The degree of the injury of nonspecific frontal and brain stem structures
      and involvement of the left hemisphere into the pathological process together
      with the right one is essential for KS reversibility.

PMID- 11505913
TI  - [Permeability of hemato-encephalic barrier in Alzheimer's disease and
      parkinsonism with cognitive disorders].
AB  - The study was made of 17 patients with expected Alzheimer's disease (AD), 29
      patients with Parkinson's disease (PD) and 7 with a expected dementia with Levy
      bodies (DLB). The severity of cognitive disorders was determined according to the
      following scales: Global Deterioration Rating Scale, Mini-mental State
      Examination, Mattis Dementia Rating Scale. Besides, the patients state was
      evaluated, in the whole, according to some scales. Permeability of hemato
      encephalic barrier was evaluated according to the blood serum levels of 3
      neurospecific proteins--neuron specific enolase, glial fibrillary protein and
      alpha-glycoprotein. Their determination was performed by ELISA method. The
      significant elevation of the levels of the proteins studied was found already on
      the early stages of the disease. Their levels were higher in the patients with
      the dementia as compared with the individuals without it. There were no
      differences in cortical, subcortical and combined types of dementia. The authors
      believe, that some of the proteins studied (neuron specific enolase, for example)
      may serve as non specific markers of cerebral degeneration.

PMID- 11505914
TI  - [Dynamics of the focal neurological disorders in stroke survivors].
AB  - A study of the neurological disorders was performed in the population of 34-80
      year-old stroke survivors. The duration of the period after the stroke was in the
      range from some weeks till 17 years. The patients were included into the computer
      post-stroke patients data bank set up in the V.M. Bekhterev Institute. The follow
      up study has found that aphasic and motor disorders regress more frequently.
      Tonic disorders of extrapyramidal character aggravate, probably, due to
      progression of the main vascular process. In patients with location of focus in
      different hemispheres a decrease of the pyramidal spasticity was observed in the
      approximately equal degree, while its increase was more often found in patients
      with right focal process as compared with the left one (22.3% and 9.2%,
      respectively). Manifestation of the amyostatic disorders was stable (72.7%) in
      patients with damage of the left hemisphere, as compared with the damage of the
      right one (50%). Efficiency of restoration of the movements was approximately
      equal in patients with cortical, subcortical and combined foci in the right or in
      the left hemisphere of the brain.

PMID- 11505915
TI  - [The evaluation of VNTR-polymorphism in the gene of dopamine transporter in men
      of different nationalities with acute alcoholic psychosis].
AB  - VNTR-polymorphism of the gene of dopamine transporter (DAT) in men of the Russian
      and Tatar nationalities with acute alcoholic psychoses was analyzed by method of
      the polymerase chain reaction. There were no differences in the distribution of
      frequencies of genotypes and alleles of DAT gene between the populations
      examined. There was association between an allele variant with 9 units of DAT
      gene repetition (in homozygous state first of all), and early development of
      alcoholic dependence and acute alcoholic psychosis.

PMID- 11505916
TI  - [Accumulation and prevalence of consequences of head injury in the population].
AB  - The paper presents some methodological problems concerning modeling of the
      processes of accumulation and prevalence of the pathological states caused by
      head injury in the population. The trend in the number of annual cases of new
      injuries of the head is estimated for at least 10 years for different age groups
      of the population. The average indices are estimated together with the limits of
      their fluctuations. Taking into consideration the mean expectation of life both
      the average annual quantity of the individuals with head injury in the anamnesis
      and probability of their accumulation are determined. This index equals to 22.22
      per 1000. The frequency of the craniocerebral traumas was estimated in comparison
      with the total quantity of head injuries: 18.7 +/- 3.18% for children; 38.6 +/-
      3.97% for the adults.

PMID- 11505917
TI  - [Psychotherapeutic service in general somatic hospital].
AB  - The paper presents the experience of the activity of psychotherapeutic department
      in general somatic hospital during 3 years. For this period specialists of this
      department (psychotherapist, psychiatrist, medical psychologist and a nurses)
      were consulted 4528 patients. Some disorders of nonpsychotic level were found in
      2915 cases. Different methods of psychotherapy resulted in either "recovery" or
      "significant improvement" in 1065 (39.5%) patients; in the "improvement"--in 1157
      (39.7%) cases, in the "insignificant improvement"--in 604 (20.7%) patients; there
      wasn't observed any effect in 89 (3.1%) cases. Psychotherapeutic service in
      general somatic hospital is thought useful.

PMID- 11505918
TI  - [Constantin von Monakow: a Russian founder of the Switzerland Neurological
      Society].

PMID- 11505919
TI  - [New aspects of therapy of Parkinson disease].

PMID- 11505920
TI  - [Some approaches to therapy of Parkinson's disease].

PMID- 11505921
TI  - [Atypical parkinsonism].

PMID- 11505922
TI  - [Forms of the clinical course of brain abscesses].

PMID- 11505923
TI  - [The role of autoimmune component in the development of nervous diseases among
      the members of fire extinguishing teams during fires in ecologically dangerous
      manufacture productions].

PMID- 11505924
TI  - [A possible application of linguistic approaches to the analysis of experiences
      of "play" in psychopathological structure of delirium].

PMID- 11505925
TI  - [High mental functions in healthy individuals and in cerebrovascular diseases].
AB  - A knowledge of time parameters of the high mental functions of the brain under
      normal and pathological conditions may serve as a key to understanding of their
      intimate mechanisms. During the first stage of the study a set of different tests
      including "word association", "paired words learning" was used to compare these
      indices in patients with atherosclerotic discirculatory encephalopathy and in
      normal individuals. The dynamics and volume of the short-term memory and
      processes of attention were evaluated. An increase of the response latencies in
      the paired words' tests and a decrease of both volume of short-term memory and
      the processes of attention were identified. Application of the tests with
      semantically similar or unlike words was informative.

PMID- 11505926
TI  - Begnign bone tumors of childhood.
AB  - The diagnosis of a bone tumor in a child can be a source of great anxiety for the
      patient, the parents, and the treating physician. Fortunately, most bone tumors
      in children are benign. Although there are a variety of benign bone tumors that
      affect skeletally immature patients, most have such characteristic clinical and
      radiographic presentations that the diagnosis can be made with reasonable
      accuracy without a biopsy. However, some benign bone tumors can simulate a
      malignant process and may be best handled by referral to a person trained in
      orthopaedic oncology for additional evaluation. Treatment alternatives are in
      part related to the Musculoskeletal Tumor Society stage of the lesion.
      Recurrences of certain lesions, such as aneurysmal bone cysts and osteoblastomas,
      can be problematic. By becoming familiar with the presentation of the more common
      benign bone tumors in children, physicians will be able to alleviate fears,
      establish a diagnosis, and make treatment recommendations in the most effective
      manner.

PMID- 11505927
TI  - Degenerative arthritis of the knee in active patients: evaluation and management.
AB  - The natural history and treatment of degenerative arthritis of the knee in active
      patients is a topic of great interest, with continually evolving concepts and
      techniques. Osteoarthritis is a spectrum of clinical entities, ranging from focal
      chondral defects to established arthrosis resulting from biologic and
      biomechanical hyaline cartilage failure. Evaluation of the active patient with
      knee arthritis should include a comprehensive history emphasizing symptom
      manifestation, activity level, and previous surgical treatment. The physical
      examination must include an evaluation of extremity alignment, gait patterns, and
      coexisting disorders of the spine and adjacent joints. Diagnostic testing is
      usually straightforward and should include the 45-degree flexion weight-bearing
      posteroanterior plain radiograph. Nonsurgical treatment modalities include
      rehabilitation, lifestyle modification, bracing, supportive devices, and medical
      management, including use of the new chondroprotective oral and injectable
      agents. Several surgical options exist, each with specific indications.
      Arthroscopic debridement can provide a positive, but often short-lived, reduction
      in the severity of symptoms. Tibial or femoral osteotomy may maintain the
      patient's active lifestyle and delay the need for arthroplasty. Unicompartmental
      and total knee arthroplasty can each provide reliable relief of symptoms but may
      not permit a return to the activities that the patient values.

PMID- 11505928
TI  - Fractures of the base of the first metacarpal: current treatment options.
AB  - Fractures of the thumb metacarpal occur most frequently at the base. These
      fractures can be subdivided into intra-articular and extra-articular types. Intra
      articular fractures present treatment challenges because they have a tendency to
      displace due to deforming forces acting at the base of the thumb. An
      understanding of the anatomy, biomechanics, and fracture pattern will aid in
      deciding on the best treatment option for each fracture type. Surgical treatment
      is recommended for unstable fractures. Anatomic restoration of the articular
      surface in Bennett and Rolando fractures is not essential to obtain a good
      functional result. However, reduction should be 1 mm or less to reduce the risk
      of radiographic arthritis. Malunion of these fractures may result in long-term
      disability. Closed reduction and percutaneous Kirschner-wire fixation is
      generally the appropriate treatment for a Bennett fracture. Rolando fractures can
      be treated with either open reduction and internal fixation or external fixation,
      depending on the size of the fracture fragments. In the case of severely
      comminuted intra-articular fractures, articular impaction has been implicated as
      one of the causes of posttraumatic arthritis. It is difficult to restore the
      articular surface in these injuries. Therefore, external fixation can be
      considered when the fracture fragments are small and there is significant soft
      tissue injury.

PMID- 11505929
TI  - Immunoageing - the cause or effect of morbidity.

PMID- 11505931
TI  - Bibliography. Current world literature. Degenerative diseases.

PMID- 11505930
TI  - In vivo models of dominant T-cell tolerance: where do we stand today?

PMID- 11505932
TI  - Bibliography. Current world literature. Movement disorders.

PMID- 11505933
TI  - Open letter to the chief medical officer.

PMID- 11505934
TI  - Will primary care trusts lead to US-style health care?

PMID- 11505935
TI  - Antidepressants and counselling for major depression in primary care. Counselling
      is not demonstrably as effective as drug treatment for depression.

PMID- 11505936
TI  - Antidepressants and counselling for major depression in primary care. Authors'
      conclusions were not justified by findings.

PMID- 11505937
TI  - Antidepressants and counselling for major depression in primary care. Measuring
      preference in primary care studies could be improved.

PMID- 11505938
TI  - Revised declaration of Helsinki. WMA will continue to revise policy as medicine
      and research changes.

PMID- 11505939
TI  - Revised declaration of Helsinki. Ethics is not just for ethicists.

PMID- 11505940
TI  - High caesarean section rates among women over 30. Effect of age is continuous and
      international.

PMID- 11505941
TI  - High caesarean section rates among women over 30. High rates may be due to
      perceived potential for complications.

PMID- 11505942
TI  - Health benefits from genetics should be basic human rights.

PMID- 11505943
TI  - Beware of cytogenetic results after successful bone marrow transplantation.

PMID- 11505944
TI  - Determinants of blood loss during primary burn excision.
AB  - BACKGROUND: Excisional therapy for burn wounds is frequently associated with
      large operative blood losses. Our objective was to identify patient and operative
      factors that affect surgical blood loss and determine strategies to minimize
      hemorrhage. METHODS: Data from 92 consecutive pediatric patients with severe
      burns (>40% total body surface area) were evaluated. Patient demographics, burn
      characteristics, operative factors, and clinical course variables were correlated
      with blood loss. Blood loss at the time of initial total burn excision was
      determined by a standardized, previously validated method. Data were analyzed
      sequentially and cumulatively through univariate and cross-sectional multivariate
      linear regression. RESULTS: Demographic factors that correlated with increased
      blood loss were older age, male sex, and larger body size. Area of full-thickness
      (third-degree) burn correlated with blood loss, whereas total burn size did not.
      High wound bacteria counts (derived from quantitative tissue cultures), total
      wound area excised, and operative time were the strongest predictors of the
      volume of operative hemorrhage. Blood loss increased with delay to primary burn
      excision at a maximum at 5 to 12 days after burn injury. CONCLUSIONS: Early
      definitive surgical therapy before extensive bacterial colonization and rapid
      operative excision is a strategy that may decrease operative hemorrhage and
      transfusion requirements during burn surgical procedures.

PMID- 11505945
TI  - Switch therapy studies.

PMID- 11505947
TI  - Pharmacoepidemiology and drug safety.

PMID- 11505946
TI  - Salt sensitivity predicts mortality independently of elevated blood pressure: a
      27-year follow-up study.

PMID- 11505948
TI  - [1st Multidisciplinary Colorectal Cancer Congress. Effectiveness of pre-operative
      radiotherapy in combination with total mesorectal excision. Preliminary results
      of the Netherland study of rectal cancer].

PMID- 11505949
TI  - [Future trends in the treatment of brain tumors. Padua, 16-17 March 2001].

PMID- 11505950
TI  - [XI. International Congress on Anticancer Treatment. New therapeutic method in
      metastatic colon cancer: oncologic surgery. Paris, February 7, 2001].

PMID- 11505951
TI  - [Evolvement of hormone therapy for breast cancer. Florence, March 14, 2001].

PMID- 11505952
TI  - Controversial Patient Rights Bill set for contentious conference.

PMID- 11505953
TI  - Employer's HMO premiums rise as high as 50%.

PMID- 11505954
TI  - Births to teens hit record low in last decade.

PMID- 11505955
TI  - Most low-income adults do not qualify for Medicaid.

PMID- 11505956
TI  - West Nile virus spreading.

PMID- 11505957
TI  - House legislation would ban cloning.

PMID- 11505958
TI  - Death rate higher in elderly with low cholesterol.

PMID- 11505959
TI  - What are the issues surrounding long-term benzodiazepine treatment for
      generalized anxiety disorder.

PMID- 11505960
TI  - Where do the "old" antipsychotics fit in today's treatment plans?

PMID- 11505961
TI  - Reduction in dental caries with four concentrations of sodium fluoride in a
      dentifrice: a meta-analysis evaluation.
AB  - Information on the effects of fluoride concentrations above 1,100 ppm in
      dentifrices is not extensive in the literature. The objective of this meta
      analysis was to examine and compare the anticaries effectiveness (in terms of
      DMFS scores) of 1,700 ppm, 2,200 ppm and 2,800 ppm F- ion (as sodium fluoride)
      dentifrices vs. an 1,100 ppm F- ion (as sodium fluoride) control dentifrice based
      on results from six double-blind, randomized clinical studies, each conducted
      over a two- to three-year period. The studies each enrolled approximately 1,200
      2,000 male and female school children per treatment group in grades I through 8,
      and were conducted in areas with low fluoride content water supplies in the
      states of Indiana, Pennsylvania, Ohio and Oregon. Separate meta-analyses were
      performed on the study results (DMFS increment scores determined by visual
      tactile examinations supplemented with radiographs) for the one-year, two-year
      and three-year examinations. Comparisons of the 1,700 ppm F-, 2,200 ppm F-, and
      2,800 ppm F- groups vs. the 1,100 ppm F- group were based on pooling the effect
      sizes for these comparisons from the individual studies. The effect sizes were
      calculated in two different ways, reflecting the analyses that were performed in
      the original studies: 1) effects based on the sample means and variances; and 2)
      effects based on the adjusted sample means and mean squared error from an
      analysis of covariance. The results obtained from this meta-analysis provide
      evidence that the use of a 2,800 ppm F- ion, as sodium fluoride, dentifrice
      results in statistically significantly lower caries increment than the use of an
      1,100 ppm F- ion, as sodium fluoride, dentifrice. This result was noted after
      one, two, and three years of dentifrice use. The 1,700 ppm F- and 2,200 ppm F-
      dentifrice groups showed some directional advantages over the 1,100 ppm F-
      dentifrice group, however the analysis did not establish these groups as
      statistically significantly better than 1,100 ppm F-. The meta-analysis based on
      analysis of covariance results was somewhat more sensitive to treatment group
      differences than the analysis based on sample means and variances, as was
      expected.

PMID- 11505962
TI  - Clinical evaluation of an automatic flossing device vs. manual flossing.
AB  - The aim of this study was to compare the effectiveness of an automatic flossing
      device to manual flossing. A total of seventy adult subjects (20 males and 50
      females) were stratified into two groups balanced for age, sex, modified gingival
      index (MGI), plaque index (PI) and bleeding sites (Eastman Bleeding Index) using
      screening data. One group was randomly assigned the automatic power flosser and
      the other group was assigned manual dental floss. The subjects were instructed to
      brush their teeth twice a day (in the morning and before bedtime) for 30 seconds
      using the provided manual toothbrush and toothpaste. They were also to use their
      assigned dental floss or automatic power flosser once in the morning following
      toothbrushing. There was no significant difference between manual flossing and
      automatic flossing with respect to the MGI and the BI. There was, however, a
      significant difference at day 15 in the PI; however, this difference was only
      0.73%. There was no significant difference in the PI at day 30 between the two
      techniques. The statistically significant difference noted in the interproximal
      PI at both day 15 and day 30 was less than 2%. Since the differences in plaque
      scores between the groups were so small, there was no apparent impact on gingival
      health since both flossers resulted in similar health benefits. Since there was a
      marked preference for the automatic flosser, patient compliance with the
      automatic flossing device may be better than with manual floss. Therefore,
      overall gingival health may benefit from this device.

PMID- 11505963
TI  - Evidence for the microbicidal activity of a chlorine dioxide-containing oral
      rinse formulation in vivo.
AB  - The ability of an oral rinse preparation, containing an admixture of the
      oxohalogen oxidants chlorite anion and chlorine dioxide, to diminish salivary
      levels of Streptococcus mutans, lactobacilli and Candida albicans was
      investigated in a group of 33 dental patients. Patients underwent oral rinsing
      episodes with the above product (20 ml for a period of 60 seconds, three times
      daily) for a total of 14 days, and subsequently repeated this exercise with
      mineral water in place of the oral rinse formulation. A group of 10 dental
      student volunteers, conducting the same oral rinsing regimens with mineral water
      in place of the oral health care product, served as a control group. Salivary
      microorganism levels were determined both prior and subsequent to the above trial
      period. The results demonstrated that biocidal oxohalogen oxidants present in the
      oral rinse formulation tested gave rise to a substantial reduction in salivary S.
      mutans and lactobacilli levels (p < 0.001 and 0.005, respectively), although the
      decrease observed in C. albicans failed to reach statistical significance. As
      expected, mineral water employed as an oral rinsing system by the same group of
      patients, or the student control group, exerted no influence on the salivary
      levels of each of these microorganisms. The therapeutic, microbial and
      biochemical ramifications of the results obtained are discussed.

PMID- 11505964
TI  - The comparative anticaries efficacy of a dentifrice containing 0.3% triclosan and
      2.0% copolymer in a 0.243% sodium fluoride/silica base and a dentifrice
      containing 0.243% sodium fluoride/silica base: a two-year coronal caries clinical
      trial on adults in Israel.
AB  - The purpose of this two-year clinical study was to provide a comparison of the
      anticaries efficacy associated with two commercially available, American Dental
      Association-accepted dentifrices: Colgate Total Toothpaste, which contains 0.3%
      triclosan and 2% copolymer in a 0.243% sodium fluoride/silica base; and Crest
      Cavity Fighting Toothpaste with Fluoristat, which contains 0.243% sodium fluoride
      in a silica base. The study was conducted in harmony with the published 1988
      American Dental Association guidelines for studies geared toward the comparison
      of fluoride dentifrices. The study employed a double-blind parallel-group design,
      and involved adults living in communities throughout Israel. Qualifying subjects
      were randomly assigned to the two treatment groups, with multiple subjects in the
      same household all assigned to the dentifrice randomly allocated to the first
      among them. Caries examinations were conducted in accordance with U.S. Food and
      Drug Administration guidelines for the clinical evaluation of drugs to prevent
      dental caries. Two calibrated examiners performed all of the measurements. After
      treatment assignment, study participants were instructed to brush their teeth at
      home with their assigned dentifrice at least twice daily. Brushing instructions
      were reinforced by indoctrination in proper oral hygiene techniques by dental
      professionals, supplemented by pamphlets supplied by the sponsor and yearly
      mailings to participants, emphasizing good oral hygiene and the need to ensure
      compliance with the study. Post-baseline examinations were performed after one
      year of product use, and again after two years of product use. Three-thousand,
      three-hundred and ninety-two (3,392) subjects completed this two-year study. For
      these subjects, the mean caries scores (DFS, decayed or filled surfaces) at
      baseline were 21.96 for the Colgate Total Toothpaste group, and 21.49 for the
      Crest Cavity Fighting Toothpaste with Fluoristat group. For caries increment
      after one year, the respective means were 1.37 for the Colgate Total Toothpaste
      group, and 1.56 for the Crest Cavity Fighting Toothpaste with Fluoristat group.
      After two years, the mean caries increments were 1.46 for the Colgate Total
      Toothpaste group, and 1.75 for the Crest Cavity Fighting Toothpaste with
      Fluoristat group. No statically significant difference was indicated between the
      treatment groups at baseline. However, for both the one-year and two-year
      increments, there was a statistically significant difference between treatment
      groups. Relative to the Crest Cavity Fighting Toothpaste with Fluoristat group,
      the Colgate Total Toothpaste group presented a 12.2% reduction in caries
      increment scores at one year, and a 16.6% reduction in caries increment scores at
      two years. In accordance with the procedures and standards provided by the
      published guidelines of the American Dental Association for the comparison of the
      anticaries efficacy of fluoride dentifrices, the results of this study support
      the conclusion that Colgate Total Toothpaste provides a superior level of coronal
      anticaries efficacy compared to Crest Cavity Fighting Toothpaste with Fluoristat.

PMID- 11505965
TI  - Impact of dental health care on dental health of children with long-term
      diseases: a nested case-control study.
AB  - The objective was to study dental health among nine-year-old long-term ill and
      disabled children and their matched controls using DMFT/dmft-indices (decayed
      missing-filled-teeth, of both permanent and deciduous teeth); to analyze
      similarities and differences of their family factors; the children's dental
      health habits which include dietary factors; to assess capabilities of the health
      care personnel in the identification of the risk groups and in the provision of
      services; and finally to investigate family satisfaction with the dental health
      care services provided. One dentist (M-L M) routinely carried out the clinical
      examinations of the children using the DMFT(dmft)-index. Only cavities extending
      to dentin were included in the DMF and dmf indices. X-rays were also used. It was
      found that less than half of the children (46%) had healthy teeth (DMFT and dmft
      both = 0), with 41% among the study group and 51% among the controls. The DMFS
      index of the longterm ill children was slightly, but not significantly greater
      than that of the controls, and these children used dental health care services
      more but their families were less satisfied with the services. The long-term ill
      children had less orthodontic care than the controls although they needed it more
      frequently, and they had a designated candy day significantly more often than the
      controls. Special diets were associated with long-term ill children, as were the
      sociodemographic factors of marital status, divorce, or stepfather present. No
      significant differences existed between the groups in toothbrushing and the use
      of fluoride products. In the status and health of teeth as measured with the
      DMFT/dmft indices, there were no statistically significant differences between
      the group of the long-term-ill children and healthy controls. Estimation of the
      focusing of care was considered successful concerning dental health, but resource
      limitations emerged and contributed to parents not being satisfied with the
      frequency dental care services offered.

PMID- 11505966
TI  - The comparative plaque removal efficacy of two advanced manual toothbrush designs
      in two independent clinical studies.
AB  - Two independent studies were conducted to evaluate and compare the clinical
      performance of two commercially available manual toothbrushes (Colgate Total
      Professional and the Oral-B Cross Action). Study I was a short-term, examiner
      blind crossover clinical trial (N = 30) designed to measure the removal of 24
      hour plaque build-up. All subjects refrained from brushing for 24 hours and were
      screened for dental plaque on the facial and lingual surfaces of all natural
      teeth using the Rustogi Modified Navy Plaque Index. Patients then received one of
      the two study toothbrushes and brushed their teeth for a timed one minute. They
      were then re-assessed for plaque. The data showed that the Colgate Total
      Professional toothbrush performed better than the Oral-B Cross Action toothbrush
      in reducing whole-mouth plaque scores (p < 0.001). Study II was a definitive six
      week, single-blind clinical trial (N = 55), conducted in harmony with American
      Dental Association guidelines, to assess the ability of the two toothbrushes to
      reduce supragingival plaque and gingivitis. In this study, the subjects were
      stratified into two balanced groups based on their baseline plaque and gingivitis
      scores. Subjects were then instructed to continue with their normal brushing
      technique twice daily for one minute with their assigned toothbrush and a
      commercially available dentifrice. Examinations for plaque (Rustogi Modified Navy
      Plaque Index), and gingivitis (Loe-Silness Gingival Index) were conducted by the
      same examiner at baseline, after three weeks, and again after six weeks. The data
      from this long-term clinical trial showed that the Colgate Total Professional
      toothbrush exhibited statistically significantly lower plaque and gingivitis
      scores than did the Oral-B Cross Action toothbrush. The magnitudes of these
      differences were 29.5% for plaque and 31.1% for gingivitis. These reductions are
      adequate to support the claim that the Colgate Total Professional toothbrush
      provides clinically superior control of supragingival plaque and gingivitis, when
      studied in accordance with the criteria provided by the 1999 Guidelines of the
      American Dental Association for determining superiority.

PMID- 11505967
TI  - Delineation of the pathogenesis of systemic lupus erythematosus by using murine
      models.

PMID- 11505968
TI  - Multiple sclerosis and gene expression profiling.

PMID- 11505969
TI  - Treatment of autoimmunity by inhibition of T cell costimulation.

PMID- 11505970
TI  - Cytokine blockade in rheumatoid arthritis.
AB  - As we enter the 2000's it is clear that cytokine blockade is an effective
      therapeutic strategy for rheumatoid arthritis. In this brief review, we will
      review the rationale for anti TNFalpha therapy, the current status of therapy and
      focus on the regulation of TNFalpha production in rheumatoid synovium. New
      approaches to studying TNF regulation in RA and of elucidating the controversial
      role of T cells in this complex disease will be described.

PMID- 11505971
TI  - Control of autoimmunity by regulatory T cells.

PMID- 11505973
TI  - Peripheral tolerance and organ specific autoimmunity.

PMID- 11505972
TI  - Autoimmunity, self-tolerance and immune homeostasis: from whole animal phenotypes
      to molecular pathways.

PMID- 11505974
TI  - Autoimmune lymphoproliferative syndrome: types I, II and beyond.

PMID- 11505975
TI  - The role of MHC class II molecules in the pathogenesis and prevention of Type I
      diabetes.

PMID- 11505976
TI  - Control of autoreactive T cell activation by immunoregulatory T cells (ART).

PMID- 11505977
TI  - Factors contributing to autoimmune disease.

PMID- 11505978
TI  - Immune tolerance and the nervous system.

PMID- 11505979
TI  - Functional role of epitope spreading in the chronic pathogenesis of autoimmune
      and virus-induced demyelinating diseases.
AB  - These results support a model of epitope spreading (Figure 4) wherein localized
      virus-specific T cell-mediated inflammatory processes lead to the
      recruitment/activation of CNS-resident APCs which can serve both as effector
      cells for myelin destruction and as APCs which efficiently process/present
      endogenous self epitopes to autoreactive T cells. Thus, inflammatory responses
      induced by viruses which trigger pro-inflammatory Th1 responses and have the
      ability to persist in genetically susceptible hosts, may lead to chronic organ
      specific autoimmune disease via epitope spreading. Regardless of the specificity
      of the T cells (myelin peptides in R-EAE or TMEV epitopes in TMEV-IDD)
      responsible for initiating myelin destruction, epitope spreading plays an
      important contributory role in the chronic disease process in genetically
      susceptible SJL mice. Epitope spreading has obvious important implications to the
      design of antigen-specific therapies for the potential treatment of MS and other
      autoimmune diseases. This process indicates that autoimmune diseases are evolving
      pathologies and that the specificity of the effector autoantigen-specific T cells
      varies during the chronic disease process.

PMID- 11505980
TI  - Perfluorooctane sulfonate in fish-eating water birds including bald eagles and
      albatrosses.
AB  - Perfluorooctane sulfonate (PFOS) was measured in 161 samples of liver, kidney,
      blood, or egg yolk from 21 species of fish-eating water birds collected in the
      United States including albatrosses from Sand Island, Midway Atoll, in the
      central North Pacific Ocean. Concentrations of PFOS in the blood plasma of bald
      eagles collected fromthe midwestern United States ranged from 13 to 2,220 ng/mL
      (mean: 330 ng/mL), except one sample that did not contain quantifiable
      concentrations of PFOS. Concentrations of PFOS were greater in blood plasma than
      in whole blood. Among 82 livers from various species of birds from inland or
      coastal U.S. locations, Brandt's cormorant from San Diego, CA, contained the
      greatest concentration of PFOS (1,780 ng/g, wet wt). PFOS was also found in the
      sera of albatrosses from the central North Pacific Ocean at concentrations
      ranging from 3 to 34 ng/mL. Occurrence of PFOS in birds from remote marine
      locations suggests widespread distribution of PFOS and related fluorochemicals in
      the environment.

PMID- 11505981
TI  - Measurements of atmospheric carboxylic acids and carbonyl compounds in Sao Paulo
      City, Brazil.
AB  - Winter atmospheric measurements of gaseous lower carbonyl and carboxylic acids
      were carried out simultaneously (in 1999) at two distinct urban sites located in
      the city of Sao Paulo, Brazil. The greater metropolitan area of Sao Paulo is the
      largest industrialized region of Latin America and has a highly polluted
      atmosphere. It has an unconventional mix of vehicle types in that a variety of
      gasoline blends, including oxygenated ones, are used. Mixing ratios of formic and
      acetic acids ranged, respectively, from 0.6 to 19.4 and from 0.1 to 10.6 ppbv in
      one of the sites studied and from 1.4 to 18.4 and from 0.4 to 6.7 ppbv in the
      other site. High values of formic to acetic ratios were found, especially in the
      latter site (average = 4.3), suggesting that photochemical production was the
      predominant source of the formic and acetic acid during the afternoon. Differing
      from the acids, levels of carbonyls were similar at both sites. Higher average
      mixing ratios of acetaldehyde and formaldehyde were found in the morning (18.9
      and 17.2 ppbv) and gradually decreased from midday (9.5 and 11.8 ppbv) to evening
      (7.2 and 10.2 ppbv). In the morning, vehicular direct emission seemed to be the
      main primary source of formaldehyde and acetaldehyde, whereas at midday and
      evening these compounds appeared to be mainly formed by photochemistry. Secondary
      photochemical production of organic acids and aldehydes (rather than primary
      emissions from vehicles) was shown to be more important in Sao Paulo's atmosphere
      from midday to evening, particularly on days with strong solar radiation.

PMID- 11505982
TI  - Changes in deposition of phytoplankton constituents in a Ca2+ polluted lake.
AB  - Systematic reductions in the deposition rate of organic C, N, P, and chlorophyll
      (Chl) are documented for Ca2+ polluted, culturally eutrophic, Onondaga Lake, NY,
      based on analyses of weekly sediment trap collections over the May-October
      interval for 10 years of the 1980-1992 period. Inputs of both nutrient-rich
      domestic waste and industrial salt waste (including Ca2+) decreased over this
      period. Constituent ratios of the collected sediment indicate phytoplankton
      biomass was the dominant source of the deposited organic C, N, and Chl.
      Substantial decreases in downward fluxes of these constituents occurred starting
      in 1987: 37, 42, 25, and 54%, on average, for organic C, N, P, and Chl,
      respectively. These reductions were driven primarily by the decreases in the
      lake's salinity and Ca2+ concentration, that resulted from the closure of a soda
      ash manufacturing facility (1986), rather than decreases in water column P
      concentrations from reductions in domestic waste loading. Three different
      mechanisms for the decreased deposition, related to the reductions in salinity
      and Ca2+ concentration, are considered: (i) decrease in coating of phytoplankton
      with CaCO3 precipitate, (ii) increased grazing of phytoplankton by large
      cladocerans, and (iii) decreases in coagulation of phytoplankton. The greater
      loss of phytoplankton biomass through deposition, driven by salt waste inputs
      from the industry, exacerbated the lake's problem of high primary production.
      This response is consistent with ecological theory for nutrient saturated
      phytoplankton growth but has not previously been demonstrated on a whole-lake
      basis.

PMID- 11505983
TI  - Analysis of organic esters of plasticizer in indoor air by GC-MS and GC-FPD.
AB  - The aim of this study was to assess the performance of a method of analyzing
      organic esters of plasticizer in indoor air by sampling air in a charcoal tube
      and extracting the esters in toluene using a gas chromatography-mass spectrometer
      (GC-MS) and flame photometric detector (FPD). An internal standardization method
      was used for the GC-MS measurement of phthalate esters, whereas an external
      calibration method was employed to determine the levels of phosphate esters by
      FPD. The instrumental detection limit, the instrumental lower limit of
      determination, and the blank and method detection limits were also determined.
      Mean recoveries of phthalate esters from the charcoal tube were 97.9-115%. Mean
      recoveries of phosphate esters were lower but reproducible. Recoveries of the
      esters from indoor air were generally greater than 80%. For all the compounds, no
      significant breakthrough was detected up to 100 microg. Thus, indoor organic
      esters could be accurately determined in the range of 0.6 x 10(-3)-23 microg/m3
      by the procedure presented here. Preliminary analysis of the organic esters
      indicated that exposure to phthalate esters via indoor air inhalation could
      constitute a significant contribution to total daily intake.

PMID- 11505984
TI  - Multielemental analysis of purpleback flying squad using high resolution
      inductively coupled plasma-mass spectrometry (HR ICP-MS).
AB  - Forty-four elements were analyzed in 21 tissues of purpleback flying squid,
      Sthenoteuthis oualaniensis, by high resolution inductively coupled plasma-mass
      spectrometry (HR ICP-MS) and inductively coupled plasma atomic emission
      spectrophotometry (ICP-AES). Greater concentrations of V, Fe, Co, Ni, Cu, Ag, Cd,
      Pb, and Bi were found in liver, pancreas, and ink sac than in other tissues. Ink
      sac concentrated remarkable levels of Ca and Sr in addition to the above
      mentioned elements. Several alkalis, alkaline earth, and rare earth elements
      preferentially accumulated in muscle. Among the hard tissues, accumulation of V
      and U in beak, Ni, Zn, and Cd in gladius and Cr in skin was prominent. K, Rb, Cs,
      Pb, Bi and some transition elements (V, Co, Cu, Zn, Ag, Cd) were significantly (p
      < 0.05) higher in the livers of adult than in juvenile squids. Sodium, alkaline
      earth, and rare earth elements were higher in the livers of juveniles than in
      adult squids.

PMID- 11505985
TI  - Alkylphenolic compounds in edible molluscs of the Adriatic Sea (Italy).
AB  - This paper reports the first group of results on alkylphenol (APE) contamination
      of seafood in the Adriatic Sea, in the framework of a national project on the
      quality of this Sea (PRISMA 2). Nonylphenol (NP), octylphenol (OP), and their
      ethoxylates (NPE and OPE) were detected in edible molluscs, either filter feeders
      or predators (clams, mussels, cuttlefishes, and squids), caught from 15 harbors
      along the Italian coast in the Adriatic Sea in 1997. NP was the compound found
      always at levels much higher than the other APEs in all the examined species. It
      reached the maximum concentration of 696 ng/g fresh weight in the squids from the
      central Adriatic Sea. OP generally occurred at levels 30 times lower than NP. OP
      was found up to a level of 18.6 ng/g in squids from central Adriatic Sea. OPE was
      the compound always spotted at the lowest concentrations, up to 0.43 ng/g. NPE
      was always below the detection limit. The pattern of contamination in the three
      areas examined was different between bivalve and cephalopod species. No
      exhaustive risk assessment for marine organisms and human health can be conducted
      on the basis of these results because data are insufficient. Yet, the occurrence
      of NP suggests a negligible risk for mussels, which represent the only molluscs
      for which data are adequate. As to the possible human health implications, the
      consumption of molluscs of the Adriatic Sea implies APE intakes that are some
      orders of magnitude lower than those responsible for toxic effects in laboratory
      animals. Despite these apparently low risks for mussels and human health, the
      reasons for concern still remain because the levels of alkylphenols found in this
      study indicate a general contamination of the Adriatic Sea even far from the
      cost. Furthermore, these levels might represent an unacceptable hazard for other
      marine organisms. Finally, they contribute to the general environmental estrogen
      pool.

PMID- 11505986
TI  - Surface chemical characterization of 2.5-microm particulates (PM2.5) from air
      pollution in Salt Lake City using TOF-SIMS, XPS, and FTIR.
AB  - Particulate matter with a diameter of 2.5 microm collected in Salt Lake City (SLC
      PM2.5) was studied using TOF-SIMS (time-of-flight secondary-ion mass
      spectrometry), XPS (X-ray photoelectron spectroscopy), and FTIR (Fourier
      transform infrared spectroscopy). The high spatial resolution and high surface
      sensitivity of TOF-SIMS allow the surfaces of individual particulates to be
      analyzed. The high mass-resolution of TOF-SIMS provides good separation of
      signals from different chemical species at the same nominal mass, and the
      extremely high detection sensitivity of TOF-SIMS makes the detection of trace
      elements possible. Metallic elements such as Li, Na, Mg, Al, K, Ca, Cr, Mn, Fe,
      Cu, Zn, Cs, and Bi were detected by TOF-SIMS on the surface of SLC PM25. The
      uranium ion U+ together with its oxide ions UO+ and UO2+ were also found.
      Inorganic compounds detected include oxides, hydroxides, nitrates, sulfates,
      silicates, borates, chlorides, etc. Organic compounds detected include
      hydrocarbons, alcohols, aldehydes, ethers, carboxylic acids, amines, amides,
      nitriles, etc. A number of polycyclic aromatic hydrocarbons (PAH) and nitrated
      polycyclic aromatic hydrocarbons were detected by TOF-SIMS. High-resolution XPS
      Cls spectrum shows functional groups such as C-O, CO2, C-CO2, C-C, and C-H and
      aromatic pi-pi* shake-up transitions. High-resolution XPS O 1s spectrum indicates
      the coexistence of different oxygen compounds on the surface of PM2.5. FTIR
      results confirm the presence of various organic compounds in SLC PM2.5 detected
      by TOF-SIMS and XPS.

PMID- 11505987
TI  - X-ray fluorescence mapping and micro-XANES spectroscopic characterization of
      exhaust particulates emitted from auto engines burning MMT-added gasoline.
AB  - The elemental distribution and compositional homogeneity in auto exhaust
      particulates emitted from methylcyclopentadienyl manganese tricarbonyl-(MMT
      )added gasoline engines have been investigated using a newly installed
      synchrotron X-ray microprobe. Two representative groups of exhaust particulate
      matter, as defined in a recent bulk X-ray absorption fine structure (XAFS)
      spectroscopic study at the Mn K-edge, were studied. The micro-X-ray absorption
      near-edge structure (XANES) spectra indicate a relatively homogeneous
      distribution of phases within a given particulate sample, down to a spatial
      extent of 40 microm (the resolution of microprobe). The micro-XANES also enabled
      analysis of several areas which displayed compositions different from the bulk
      sample, supporting the general theory describing manganese species formation in
      the exhaust. The ability to evaluate small regions also enabled direct
      verification of manganese sulfate from the S XANES despite the vast excess of
      sulfur present in other forms. The presence of a chloride compound, introduced
      through the sample dilution air and engine intake air, was also revealed. The
      study demonstrates the value of the combined X-ray microfluorescence with
      excitation by polychromatic radiation for elemental mapping and micro-XANES
      spectroscopy for chemical speciation in the study of dilute environmental
      materials containing low-Z constituents such as Cl, S, and P.

PMID- 11505988
TI  - Formation of aerosol particles from reactions of secondary and tertiary
      alkylamines: characterization by aerosol time-of-flight mass spectrometry.
AB  - In ambient field studies conducted with aerosol time-of-flight mass spectrometry
      (ATOFMS), individual particle mass spectra commonly contain ion peaks at
      mass/charge (m/z) 86, 101, 102, and 118. Particles with mass spectra containing
      these peaks show a strong correlation with high relative humidity and low
      temperatures. In an effort to identify these peaks, a series of smog chamber
      studies were conducted probing the chemistry of secondary and tertiary
      alkylamines. Specifically, in separate studies, trimethylamine, di- and
      triethylamine, and di- and tripropylamine were reacted in a 1 m3 Teflon outdoor
      smog chamber with naturally occurring levels of gas phase oxidants in ambient
      air. The aerodynamic sizes and individual mass spectra of the resulting aerosol
      particles were acquired continuously using aerosol time-of-flight mass
      spectrometry (ATOFMS). Both oxidation and acid-base reactions between amines and
      acids commonly present in the atmosphere (i.e., nitric and sulfuric acid) appear
      to play roles in the formation and chemistry of organic nitrogen-containing
      particle phase species. Ion peaks in the individual particle mass spectra
      indicate the presence of alkyl ammonium salts, as well as other tentatively
      identified organic N-containing compounds formed by oxidation processes. Also,
      for the first time, tertiary alkylamine-N-oxides have been identified as
      alkylamine oxidation products in the aerosol particle phase. Smog chamber
      reactions involving triethylamine produce ATOFMS mass spectra with similar ion
      peak combinations as those observed in the spectra of particles commonly detected
      in ambient and vehicular source characterization studies. The results of this
      study suggest that amine chemistry involving gas-to-particle conversion and
      photooxidation processes may play a significant role in particle formation in
      regions with high amine concentrations.

PMID- 11505989
TI  - Photolytic behavior of polycyclic aromatic hydrocarbons in diesel particulate
      matter deposited on the ground.
AB  - To clarify the photolytic behavior of polycyclic aromatic hydrocarbons (PAHs) in
      diesel particulate matter (DPM) deposited on the ground, we determined the rate
      constants and half-lives for the photodegradation of benzo[a]pyrene (BaPy),
      phenanthrene (Phe), fluoranthene (Flrt), pyrene (Py), and chrysene (Ch) in air
      for three probable cases: (1) DPM is placed on an inert surface, (2) DPM is mixed
      with soil, and (3) PAHs are leached from DPM and adsorbed to soil. We found that
      BaPy and Phe degraded relatively quickly in case 1. However, in case 2, these
      PAHs degraded more slowly due to the effect of the presence of soil. Flrt, Py,
      and Ch were stable. In case 3, photodegradation of adsorbed PAHs in soil was
      strongly inhibited as a function of soil depth. Although these findings were
      obtained at extreme light intensities, they may occur under real world
      conditions. Conversion factors for obtaining rate constants and half-lives for
      PAHs on the ground under sunlight are presented. We conclude that under the
      average intensity of sunlight in Tokyo, photodegradation of PAHs in DPM deposited
      on an inert surface is very slow.

PMID- 11505990
TI  - Rhizosphere bacteria mobilize Zn for hyperaccumulation by Thlaspi caerulescens.
AB  - Thlaspi caerulescens has a remarkable ability to hyperaccumulate Zn from soils
      containing mostly nonlabile Zn. The present study shows that rhizosphere microbes
      play an important role in increasing the availability of water-soluble Zn in
      soil, thus enhancing Zn accumulation by T. caerulescens. The addition of bacteria
      to surface-sterilized seeds of T. caerulescens sown in autoclaved soil increased
      the Zn concentration in shoots 2-fold as compared to axenic controls; the total
      accumulation of Zn was enhanced 4-fold. When the same experiment was conducted
      with Thlaspi arvense, a nonaccumulator, bacteria had no effect on shoot Zn
      accumulation although they increased water-soluble Zn concentrations available to
      both Thlaspi species by 22-67% as compared to the axenic controls. Further
      evidence that bacteria increase the availability of water-soluble Zn in soil was
      obtained when liquid media that had supported bacterial growth mobilized 1.3-1.8
      fold more Zn from soil as compared to axenic media. Other experiments with agar
      media showed that bacteria did not facilitate an increase in the rate of soluble
      Zn transport into the root nor did they enlarge the surface area of the roots of
      either Thlaspi species. Thus, the bacterially mediated increase in the
      dissolution of Zn from the nonlabile phase in soil may enhance Zn accumulation in
      T. caerulescens shoots.

PMID- 11505991
TI  - Microbes show promise for bioremediating plutonium.

PMID- 11505992
TI  - Sorption and desorption behavior of organotin compounds in sediment-pore water
      systems.
AB  - Sediments contaminated with organotin compounds (OTs), in particular
      triorganotins (TOTs), are abundant in areas with high shipping activities. To
      assess the possible remobilization of these highly toxic compounds from such
      sediments, a profound understanding of their sorption/desorption behavior is
      necessary. In this work the extent and reversibility of sorption of OTs to
      sediments has been investigated using contaminated freshwater harbor sediments
      and two certified OT containing marine sediments. Experiments conducted with
      perdeuterated OTs showed that sorption of OTs to sediments is a fast and
      reversible process involving primarily particulate organic matter (POM)
      constituents as sorbents. The organic carbon-normalized sediment-water
      distribution ratios (DOC, expressed in L/kgOC) determined in the laboratory were
      consistent with in-situ DOCs obtained from OT concentrations measured in sediment
      and pore water samples from two dated sediment cores. For both butyl- and
      phenyltin compounds the log DOC values were in the range of 4.7-6.1, and the
      following sequence was observed: DOC (tri-OT) > or = DOC (di-OT) > or = DOC (mono
      OT). However, the differences were much less pronounced than would have been
      expected for hydrophobic partitioning of the corresponding compounds into POM.
      These results support our hypothesis from earlier work with dissolved humic acids
      that OT sorption to sediments occurs primarily by reversible formation of
      (innerspere) complexes between the tin atom and carboxylate and phenolate ligands
      present in POM. Because of the high DOC values (i.e. log DOC > or = 4) the
      diffusion of OTs from deeper sediments to the surface will be rather slow, and
      thus a major release from undisturbed sediments is not expected. However, because
      OTs readily desorb, any resuspension of contaminated sediments (e.g., by the
      tide, storms or dredging activities) will lead to enhanced OT concentrations in
      the overlaying water column. Furthermore, in contrastto polycyclic aromatic
      hydrocarbons (PAH) where large fractions may be tightly bound (in)to soot or
      other carbonaceous materials, OTs will be more readily bioavailable due to the
      fast and reversible sorption/desorption behavior.

PMID- 11505993
TI  - Implications of aqueous silica sorption to iron hydroxide: mobilization of iron
      colloids and interference with sorption of arsenate and humic substances.
AB  - This work highlighted practical implications of aqueous silica sorption to iron
      hydroxide in natural and engineered systems. Two types of surfaces were prepared
      by exposing 10 mg/L preformed Fe(OH)3 to aqueous silica (0-200 mg/L as SiO2) for
      periods of 1.5 h or 50 days. After 1.5 h, the concentration of iron passing
      through a 0.45 microm pore size filter at pH 6.0-9.5 was always negligible, but
      if zeta potential < or =-15 mV as much as 35% of the iron passed through filters
      after 50 days of aging. When arsenate was added to 10 mg/L iron hydroxide
      particles equilibrated with aqueous silica for 1.5 h, percentage arsenate
      removals were high. In contrast, if silica was preequilibrated with iron for 50
      days, arsenate removals decreased markedly at higher pH and aqueous silica
      concentrations. Similar trends were observed for humic substances, although their
      removal was nearly completely prevented at pH 8.5 at SiO2 concentrations above 50
      and 10 mg/L at 1.5 h and 50 days exposure, respectively. The mechanism of
      interference was hindered sorption to the iron hydroxide surface.

PMID- 11505994
TI  - Coal council finds power at existing plants.

PMID- 11505995
TI  - Impact of peroxidase addition on the sorption-desorption behavior of phenolic
      contaminants in surface soils.
AB  - The impact of peroxidase addition on sorption-desorption of phenol, o-cresol, 2,4
      dichlorophenol (DCP), and 1-naphthol was evaluated using two surface soils.
      Target chemicals were added to soils as single solutes or binary mixtures. Seven
      day adsorption studies were followed by sequential fill-and-draw extractions with
      synthetic groundwater. Addition of horseradish peroxidase (HRP) with H2O2 was the
      primary treatment evaluated. HRP-mediated sorption enhancementwas related to
      contaminant solubility and increased in the order: naphthol < DCP < cresol <
      phenol. Little or no competition was observed in the presence of cosolutes.
      Contaminant desorption from soils was dramatically reduced upon HRP addition.
      Reduction in desorption was quantified using the Hysteresis Index and interpreted
      as attenuation of contaminant mobility. Desorption data predicted that mobility
      reductions followed the order: naphthol < DCP < cresol < phenol. It is believed
      that enzyme addition resulted in the production of hydrophobic polymers that, due
      to their low aqueous solubilities, readily partitioned on to the solid-phase. The
      adsorbed polymers were less likely to partition into the aqueous phase than the
      parent phenols resulting in a reduced risk to the environment.

PMID- 11505996
TI  - Chromium diffusion and reduction in soil aggregates.
AB  - The distribution of metal contaminants such as chromium in soils can be strongly
      localized by transport limitations and redox gradients within soil aggregates.
      Measurements of Cr(VI) diffusion and reduction to Cr(III) were obtained in soil
      columns representing transects into soil aggregates in order to quantify
      influences of organic carbon (OC) and redox potentials on Cr transport distances
      and microbial community composition. Shifts in characteristic redox potentials,
      and the extent of Cr(VI) reduction to Cr(III) were related to OC availability.
      Depth profiles of Cr(VI, III) obtained with micro X-ray absorption near edge
      structure (micro-XANES) spectroscopy reflected interdependent effects of
      diffusion and spatially dependent redox potentials on reduction kinetics and
      microbial community composition. Shallow diffusion depths (2-10 mm) and very
      sharply terminated diffusion fronts in columns amended with OC (80 and 800 ppm)
      reflected rapid increases in Cr reduction kinetics over very short (mm)
      distances. These results suggest that Cr contamination in soils can be restricted
      to the outsides of soil aggregates due to localized transport and rapid reduction
      and that bulk sample characterization is inadequate for understanding the
      controlling biogeochemical processes.

PMID- 11505997
TI  - Dumping of mining wastes under scrutiny.

PMID- 11505998
TI  - An isomer prediction model for PCNs, PCDD/Fs, and PCBs from municipal waste
      incinerators.
AB  - Isomer patterns of polychlorinated naphthalenes (PCNs), polychlorinated dibenzo-p
      dioxins (PCDDs), polychlorinated biphenyls (PCBs), and polychlorinated
      dibenzofurans (PCDFs) from municipal waste incinerators (MWIs) were predicted by
      a model based on symmetry numbers and preferential chlorination positions. Fly
      ash isomer patterns from five stoker and seven fluidized bed incinerators were
      compared to validate the prediction model. The isomer patterns of the highly
      chlorinated PCN homologues from stoker type incinerators were successfully
      predicted. The relative equilibrium concentrations of tetrachloronaphthalenes
      (TeCNs), calculated by an ab initio method, cannot explain the field isomer
      patterns. Formation pathways involving chlorophenol precursor condensation
      reactions should be examined to see whether these isomer patterns provide a
      better fit to the field PCDD data. The PCB isomer patterns were fit reasonably
      well, but this finding could merely be an artifact of the limited data and the
      large number of isomers. The prediction equations of PCDFs, revised from prior
      work to include a symmetry number for each isomer, represented the field data
      patterns for the higher chlorinated isomers very well. Successful prediction of
      isomer patterns for partial homologue ranges suggests that these patterns are
      determined by a mechanism governed by Cl-position-specific preferences.

PMID- 11505999
TI  - The effects of pH and surface composition on Pb adsorption to natural freshwater
      biofilms.
AB  - Two dominant variables that control the adsorption of toxic trace metals to
      suspended particulate materials and aquatic surface coatings are surface
      composition and solution pH. A model for the pH-dependent adsorption of Pbto
      heterogeneous particulate surface mixtures was derived from experimental
      evaluation of Pb adsorption to laboratory-derived surrogates. The surrogate
      materials were selected to represent natural reactive surface components. Pb
      adsorption to both the laboratory surrogates and natural biofilms was determined
      in chemically defined solutions under controlled laboratory conditions. Pb
      adsorption was measured over a pH range of 5-8, with an initial Pb concentration
      in solution of 2.0 microM. The surface components considered include amorphous Fe
      oxide, biogenic Mn oxide produced by a Mn(II) oxidizing bacterium (Leptothrix
      discophora SS-1), Al oxide, the common green alga Chlorella vulgaris, and
      Leptothrix discophora SS-1 cells. A linearization of Pb adsorption data for each
      adsorbent was used to quantify the relationship between Pb adsorption and pH. The
      parameters for individual adsorbents were incorporated into an additive model to
      predict the total Pb adsorption in multiple-adsorbent natural surface coatings
      that were collected from Cayuga Lake, NY. Pb adsorption experiments on the
      natural surface coatings at variable pH were utilized to verify the additive
      model predictions based on the pH dependent behavior of the experimental
      laboratory surrogates. Observed Pb adsorption is consistent with the model
      predictions (within 1-24%) over the range of solution pH values considered. The
      experimental results indicate that the combination of Fe and biogenic Mn oxides
      can contribute as much as 90% of Pb adsorbed on Cayuga Lake biofilms, with the
      dominant adsorbent switching from Mn to Fe oxide with increasing pH.

PMID- 11506000
TI  - Discord over snowmobiles.

PMID- 11506001
TI  - High levels of monoaromatic compounds limit the use of solid-phase
      microextraction of methyl tert-butyl ether and tert-butyl alcohol.
AB  - Recently, two papers reported the use of solid-phase microextraction (SPME) with
      poly(dimethylsiloxane)(PDMS)/Carboxen fibers to determine trace levels of methyl
      tert-butyl ether (MTBE) and tert-butyl alcohol (tBA) in water. Attempts were made
      to apply this technique to the analysis of water samples containing high levels
      of benzene, toluene, ethylbenzene, xylenes, and trimethylbenzenes (BTEXsTMBs) as
      would be expected at leaking underground storage tank sites. It was found that
      when the sample contained total aromatic compounds above 1 ppm, the response of
      the internal standards, deuterated MTBE and tBA, dropped by more than 65%. As
      this decrease in internal standard peak area was unacceptable, a static headspace
      method was used instead. This headspace method was used successfully to analyze
      groundwater from 670 monitoring wells at 74 service stations located in the
      northeast United States. In these monitoring wells, 30% of the samples contained
      total BTEXsTMBs above 1 ppm. If the SPME method was used to analyze these
      samples, dilution of more than 200 samples would be required to minimize the
      adverse matrix effect that high aromatic content had on the internal standard
      peak area.

PMID- 11506002
TI  - Field-deployable sniffer for 2,4-dinitrotoluene detection.
AB  - A field-deployable instrument has been developed to detect low-level 2,4
      dinitrotoluene (2,4-DNT) vapors. The system is based on previously developed
      artificial nose technology and employs an array of sensory materials attached to
      the distal tips of an optical fiber bundle. Both semiselective and nonspecific,
      cross-reactive sensors were employed. Each sensor within the array responds
      differentially to vapor exposure so the array's fluorescence response patterns
      are unique for each analyte. The instrument is computationally "trained" to
      discriminate target response patterns from nontarget and background environments.
      This detection system has been applied to detect 2,4-DNT, an analyte commonly
      detected on the soil surface above buried 2,4,6-trinitrotoluene (TNT) land mines,
      in spiked soil and aqueous and ground samples. The system has been characterized
      and demonstrated the ability to detect 120 ppb 2,4-DNT vapor in blind (unknown)
      humidified samples during a supervised field test.

PMID- 11506003
TI  - Determination of endocrine-disrupting phenolic compounds and estrogens in surface
      and drinking water by HRGC-(NCI)-MS in the picogram per liter range.
AB  - A method for the analysis of phenolic estrogenic active compounds in surface and
      drinking water in the picogram per liter range is described. Besides the widely
      used monomer bisphenol A, 4-tert-octylphenol [4-(1,1,3,3-tetramethylbutyl)phenol]
      and the technical isomer mixture of 4-nonylphenol; phenolic steroid hormones such
      as the endogenous estrogens estrone, 17alpha-estradiol, and 17beta-estradiol; and
      the exogenous estrogen 17alpha-ethinylestradiol were determined in water at the
      20-200 pg/L level. Water samples from 1 to 5 L were extracted by solid-phase
      extraction (SPE) on a cartridge system containing LiChrolut EN as sorbent. The
      phenols and steroids were converted into their pentafluorobenzoylate esters in an
      extractive derivatization reaction. The derivatives were then determined by high
      resolution gas chromatography with negative chemical ionization mass
      spectrometric detection (HRGC-(NCI)-MS) in the selected ion mode (SIM). All
      results were also confirmed by HRGC with electron capture detection (ECD). This
      highly sensitive and specific method gives a limit of detection (LOD) of 20 pg/L
      for bisphenol A and 4-tert-octylphenol in drinking water samples and 50 pg/L in
      STW effluent, respectively. The LODs for technical 4-nonylphenol, 17alpha
      ethinylestradiol, and other estrogens are in the range of 50 pg/L in drinking
      water to 200 pg/L in STW effluent, respectively. In all river water samples in
      southern Germany, bisphenol A was found in concentrations ranging from 500 pg/L
      up to 16 ng/L, 4-nonylphenol was from 6 up to 135 ng/L, and the steroids were
      from 200 pg/L up to 5 ng/L. In drinking water, bisphenol A was found in
      concentrations ranging from 300 pg/L to 2 ng/L, 4-nonylphenol was from 2 to 15
      ng/L, 4-tert-octylphenol was from 150 pg/L to 5 ng/L, and the steroids were from
      100 pg/L to 2 ng/L. Mean recoveries over the whole analytical protocol, measured
      in bidistilled water, generally exceeded 70%. These results indicate that
      environmental endocrine-disrupting estrogens are not completely removed in the
      process of sewage treatment but are carried over into the general aquatic
      environment. After ground passage, they can eventually be found in drinking
      water.

PMID- 11506004
TI  - A new instrument to measure gaseous nitrous acid (HONO) in the atmosphere.
AB  - A new in situ instrument (LOPAP: long path absorption photometer) to measure
      gaseous nitrous acid (HONO) using wet chemical sampling and photometric detection
      has been developed. This instrument is aimed to overcome the known problems with
      current HONO measurement techniques and was designed to be a cheap, sensitive,
      compact, and continuouslyworking HONO monitorfor ambient air measurements in the
      troposphere or for measurements of higher concentrations e.g. in smog chambers,
      in exhaust gases, and in indoor environments. Laboratory investigations were
      carried outto characterize the instrument components with respect to collection
      efficiency, optimum dye formation, optimum detection, and interfering species.
      Detection limits ranging from approximately 3 to 50 pptV have been obtained with
      response times from 4 to 1.5 min, respectively, using different instrument
      parameters. The accuracy of the measurements is in the range between +/-(10-15)%.
      The validation of the instrument was performed in the laboratory for HONO
      concentrations of 3 and 30 ppbV using ion chromatography and with a DOAS
      (differential optical absorption spectrometer) instrument in a large outdoor smog
      chamber in the range from 0.1 to 20 ppbV. The deviations were well within the
      errors of the measurements; however, when comparing the data with the DOAS
      instrument systematically higher values were found with the LOPAP instrument.

PMID- 11506005
TI  - Australian vaccine blocks ruminant burps.

PMID- 11506006
TI  - California salt marsh contaminates swimming beach.

PMID- 11506007
TI  - Determination of perchlorate in tobacco plants and tobacco products.
AB  - Previous field and laboratory studies with vascular plants have shown that
      perchlorate is transported from perchlorate fortified soils and is accumulated in
      the plant tissues and organs. This paper contains results of preliminary
      investigations on the occurrence of perchlorate in tobacco plants grown in soils
      amended with a fertilizer whose nitrogen content is derived from naturally
      occurring sodium nitrate (Chile saltpeter). Ion chromatography (IC) and capillary
      electrophoresis (CE) were used for quantitative analysis, while nuclear magnetic
      resonance (NMR) spectroscopy was used for qualitative analysis of perchlorate.
      Results show that perchlorate is accumulated by tobacco plants into the leaves
      from soils amended with fertilizers that contain perchlorate. Also, perchlorate
      can persist over an extended period of time and under a variety of industrial
      processes as shown by its presence in off-the-shelf tobacco products including
      cigarettes, cigars, and pouch and plug chewing tobaccos in concentrations ranging
      from nd to 60.4 +/- 0.8 mg/kg on a wet weight basis.

PMID- 11506008
TI  - Enhanced effect of in-situ generated ammonium salts aerosols on the removal of
      NOx from simulated flue gas.
AB  - The combined removal of sulfur dioxide (SO2, up to 3,000 ppm) and nitrogen oxides
      (NO and NO2, up to 1,200 ppm) has been investigated in a bench-scale pulsed
      corona enhanced wet electrostatic precipitator (wESP) with the optional injection
      of ammonia and/or ozone. The reaction of ammonia with SO2 produces submicron
      aerosols under certain conditions. Experiments have shown the feasibility of
      combined SO2 and NOx removal from simulated flue gases by the action of these in
      situ generated aerosols. The mechanisms for NOx removal include oxidation of NO
      to NO2 and subsequent absorption of NO2 into the water wall of the wESP. The
      results have shown that injecting NH3 (NH3/NOx molar ratio 1) resulted in NOx
      removal of approximately 13% in a simulated combustion flue gas. Injecting 200
      ppm ozone (no ammonia) increased NO conversion to 35% by oxidation, but total NOx
      removal increased to only 17%. Without the formation of ammonium salts aerosols
      (e.g., without SO2 in the gas), co-injection of ammonia and ozone increased NO
      conversion to 60% and NOx removal to 40%. However, high NOx removals were
      measured in simulated flue gas that contained NH3, SO2, and ozone. The total NOx
      removal efficiency was 79% when the ammonium salts aerosols were formed in the
      presence of 2400 ppm SO2, 312 ppm O3, and 2,900 ppm NH3. The energy efficiency of
      collection improved by approximately 250% for SO2 removal and more than 4700% for
      NOx removal under these conditions. It was determined that the ammonium salts
      aerosols produced from the reaction of ammonia and sulfur dioxide substantially
      enhanced total NOx removal.

PMID- 11506009
TI  - Barrier-controlled monitored natural attenuation.
AB  - Three existing technologies (source containment, source reduction, and monitored
      natural attenuation) are integrated in barrier-controlled monitored natural
      attenuation (BCMNA)--a new approach for managing plumes of contaminated
      groundwater and remediating contaminated sites. The basic BCMNA concept uses a
      low-permeability, nonreactive barrier to release contaminants into an aquifer at
      a rate that optimizes natural attenuation. A simplified, one-dimensional model of
      the process is developed, and a hypothetical example of BCMNA is presented for a
      site contaminated with benzene. The analytical solution is used to demonstrate
      how contaminant concentrations can be controlled at a downgradient point of
      environmental compliance by manipulating design variables. BCMNA provides a
      greater degree of process control and risk reduction than monitored natural
      attenuation alone. BCMNA also holds promise for reducing remediation costs
      because (1) barriers can be constructed relatively inexpensively and (2) a cost
      effective amount of source reduction can be applied inside the contained area
      with the BCMNA system remaining in place to safely complete the remediation
      process after source reduction is terminated. Further numerical modeling and a
      demonstration project are recommended to address important details and prove the
      concept.

PMID- 11506010
TI  - Estrogenic compounds in wood pulp mill effluents.

PMID- 11506011
TI  - A continuous system for Fe0 reduction of nitrobenzene in synthetic wastewater.
AB  - Nitrobenzene is a major environmental pollutant, and its degradation is
      difficultto achieve. Hence, a chemical reduction pretreatment is sought in this
      research, before the resulting aniline can be treated by enzyme-mediated
      oxidative polymerization. Zerovalent iron (Fe0) has been successfully employed to
      reduce nitrobenzene to aniline in synthetic wastewater in both batch and
      continuous flow reactors. The concentration of nitrobenzene studied was thatwhich
      would be present in industrial wastewater streams (millimolar, 123 ppm), a
      concentration range considerably higher than those studied previously with
      groundwater by other researchers. Anaerobic conditions were maintained in the
      reactors by including Na2SO3 as an oxygen scavenger in the presence of
      CoCl2.6H2O, which acted as a catalyst. Batch reactors exhibited adsorption of
      aniline on the Fe0, which could be described by a langmuir isotherm. A 200 g Fe0
      (particle size: 1-2 mm) bed completely converted 1 mM of nitrobenzene flowing
      upward for about 600 pore-volumes before experiencing flow reduction due to
      clogging due to corrosion products. Green-black precipitates (Fe0 corrosion
      products) were formed at the influent end of the column which were identified as
      maghemite.

PMID- 11506012
TI  - Hyperaccumulation of Zn by Thlaspi caerulescens can ameliorate Zn toxicity in the
      rhizosphere of cocropped Thlaspi arvense.
AB  - The metal hyperaccumulating plant Thlaspi caerulescens is effective in depleting
      plant-available metals from the soil. We hypothesized that this reduction of
      toxic metals in the rhizosphere of T. caerulescens would increase the growth of
      less metal-tolerant plants with their roots permitted to intermingle and develop
      coincident rhizospheres. The extent of rhizosphere interaction between T.
      caerulescens and a coplanted nonaccumulator species, Thlaspi arvense, was
      controlled using barriers. Two media with elevated concentrations of water
      extractable Zn were prepared by enriching one soil with zinc oxide (ZnO) or zinc
      sulfide (ZnS). The shoot mass of T. arvense was increased by 30% when its roots
      were permitted to intermingle with those of T. caerulescens in the ZnO treatment.
      The concomitant 2-3-fold reduction in shoot Zn concentration in T. arvense
      confirmed that its improved growth was associated with reduced uptake and
      phytotoxicity of Zn. Thlaspi arvense also showed increased growth and reduced
      metal uptake when cocropped with T. caerulescens in the ZnS treatment. We
      conclude that the strong Zn accumulation by T. caerulescens might enhance the
      establishment and development of surrounding less-tolerant species on soils that
      are naturally- or anthropogenically-enriched with metals.

PMID- 11506013
TI  - Investigation of the photocatalytic activity of TiO2--polyoxometalate systems.
AB  - The present study reports the investigation of polyoxometalate catalyzed electron
      transfer from the conduction band of photoexcited TiO2 to molecular oxygen. The
      oxidation of 1,2-dichlorobenzene (DCB) was used as an index reaction for
      evaluating the photocatalyst systems TiO2-PW12O40(3-), TiO2-SiW12O40,4- and TiO2
      W10O32(4-) in oxygenated aqueous solution. Addition of these polyoxometalate
      (POM) anions to TiO2 suspensions resulted in significant rate enhancement for DCB
      oxidation. Photodegradation kinetics exhibited [POM] dependence, experiencing
      different maximum (k = 0.0318 min(-1), 0.0108 min(-1), and 0.0066 min(-1)) for
      each POM at different [POM] (0.1 mM PW12O40(3-), 0.07 mM SiW12O40,4- and 1 mM
      W10O32,4-respectively). The probability that the difference in the adsorption
      affinity of POMs on TiO2 surface could account for the observed ranking of
      photodegradation rates was ruled out by adsorption isotherm experiments that
      revealed similar binding constants for each POM (467 M(-1), 459 M(-1), and 417 M(
      1) for PW12O40(3-), SiW12O40(4-), and W10O32(4-), respectively). DCB degradation
      over TiO2 with O2 or POM+O2 systems can be modeled by the Langmuir-Hinshelwood
      (saturation kinetics) model. The concentration-independent rate constants (kL-H)
      for TiO2-O2, TiO2-W10O32(4-), TiO2-SiW12O40(4-), and TiO2-PW12O40(3-) were
      0.0818, 0.152, 0.421, and 0.638 min(-1), respectively. An analysis of deltaG for
      electron transfer from the conduction band of TiO2 to POMs in this study shows
      that the electron transfer takes place even when it is endothermic.

PMID- 11506014
TI  - Oxidation of 4-chloro-3-methylphenol in pressurized hot water/supercritical water
      with potassium persulfate as oxidant.
AB  - 4-Chloro-3-methylphenol (c = 2.0 mM), representing a model pollutant, was
      oxidized in pressurized hot water and in supercritical water in a continuous flow
      system. Potassium persulfate was used as oxidant in concentrations of 8.0 and
      40.0 mM. Contact times (reaction times) were 3-59 s, temperatures 110-390 degrees
      C, and pressures 235-310 bar. A wide temperature range was tested to determine
      the range over which potassium persulfate can be used effectively. Good oxidation
      efficiencies for 4-chloro-3-methylphenol were obtained at both oxidant
      concentrations and with short contact times at temperatures clearly underthe
      critical temperature of water; total organic carbon content of the effluent was
      low under optimized conditions. Corrosion, measured as nickel and chromium
      concentrations of the effluent, was more severe at oxidant concentration of 40.0
      mM. Sulfate was present in the effluent in high concentrations. Sulfate is the
      limiting factor in the use of potassium persulfate in wastewater treatment and
      requires further water treatment.

PMID- 11506015
TI  - Marine monitoring in near real time.

PMID- 11506016
TI  - Polycysteine and other polyamino acid functionalized microfiltration membranes
      for heavy metal capture.
AB  - Polycysteine and other polyamino acid functionalized microfiltration membrane
      sorbents work exceptionally well for the removal and recovery of toxic heavy
      metals from aqueous streams. These are high capacity sorbents (0.3-3.7 mg/cm2)
      with excellent accessibility and selectivity for heavy metals, such as Hg(II),
      Pb(II), and Cd(II) over nontoxic components such as calcium. Polycysteine
      functionalized membranes work particularly well for metals such as Hg(II) and
      Cd(II), even in high total dissolved solids containing streams. Parameters such
      as permeate flow rate,feed metal concentration, and counterion (for Hg(II)) have
      also been found to influence sorbent behavior. For multicomponent systems,
      polyglutamic acid functionalized membranes have been found to selectively sorb
      Pb(II) versus Cd(II). Selective sorption of Cr(III) has also been observed with
      actual waste streams containing several heavy metals, hardness, and high sodium
      (2,000 mg/L). The high capacity, site accessibility, and ease of regeneration of
      these membrane-based sorbents make them ideal for environmental separations when
      volume reduction or selective recovery is required.

PMID- 11506017
TI  - Mineralization of CCl4 with copper oxide.
AB  - Experimentally, CCl4 was effectively mineralized by CuO to yield stable inorganic
      species of CO2 and CuCl2 (CCl4 + 2CuO --> 2CuCl2 + CO2). High CCl4 conversions
      (63-83%) were found in the mineralization process performed at 513-603 K for 10
      30 min. Using X-ray-absorption near edge structure (XANES) and X-ray
      photoelectron spectroscopies, we found that most CuCl2 was encapsulated in the
      CCl4-mineralized product solid (mineralization at 513 K for 30 min). At higher
      mineralization temperatures (563-603 K), CuCl2 was found to be predominant on the
      surfaces of the mineralization product. Speciation of copper in the
      mineralization product solid was also studied by extended X-ray absorption fine
      structure (EXAFS) spectroscopy. Bond distances of Cu-O and Cu-Cl in the CCl4
      mineralized product solid were 1.93-1.94 and 2.10-2.12 , respectively, which were
      greater than those of normal CuO and CuCl2 by 0.03-0.07 A. The increase of the
      bond distances for Cu-O and Cu-Cl might be due to Cl insertion and concomitant
      structural perturbation of unreacted CuO in the mineralization process. Forthe
      second shell around copper atom, bond distances of Cu-(O)-Cu also increased by
      0.03-0.05 A, and the coordination numbers of Cu-O and Cu-(O)-Cu decreased, as
      expected, in the mineralization process. In addition, stoichiometrically excess
      oxygen atoms were found on the solid surfaces, and they might play an important
      role in the mineralization of CCl4, leading to the formation of CO2 and Cl.
      Chloride atoms might be further captured by CuO, yielding CuCl2 in the
      mineralization process. This work exemplifies the utilization of X-ray
      spectroscopies (XANES, EXAFS, and XPS) to reveal the speciation and possible
      reaction pathway in a very complex mineralization process in detail.

PMID- 11506018
TI  - Adsorption of SO2 on sewage sludge-derived materials.
AB  - Sewage sludge-derived materials carbonized at temperatures between 400 and 950
      degrees C were used for adsorption of sulfur dioxide from dry and moist air. The
      materials were characterized using sorption of nitrogen and thermal analysis. The
      sulfur dioxide capacity was measured according to a laboratory-developed
      breakthrough test. It was found that the capacity of the adsorbents increases
      with increasing temperature of carbonization. It is likely that during
      carbonization at high temperatures such catalytic metals as calcium become
      active. They play a significant role in the SO2 removal process by neutralization
      of sulfuric acid formed as a result of oxidation of sulfur dioxide in wet
      conditions. Besides sulfuric acid, various sulfur-containing salts are formed. It
      was shown that, after their removal using waterwashing,the SO2
      capacitysignificantly decreased.

PMID- 11506019
TI  - Comment on "Calcium bisulfite oxidation rate in the wet limestone--gypsum flue
      gas desulfurization process".

PMID- 11506020
TI  - Environmental chemistry in the undergraduate laboratory.

PMID- 11506021
TI  - Unraveling the role of aerosols in climate change.

PMID- 11506022
TI  - Study on second harmonic generation of 10-hydrocarbylacridones.
AB  - Values of second-order polarizabilities (beta(xxx)), the composite magnitude
      (beta(CT microg)) of molecular hypersusceptibilities and the second harmonic
      generation (SHG) of microcrystal were used to characterize and evaluate the
      second-order nonlinear optical performance of 10-hydrocarbylacridones. Using
      Nd:YAG as a laser source, the SHG values of these compounds in powder as compared
      with urea powder were obtained, compared with the calculated values of beta(CT
      microg) and beta(xxx) found by solvatochromic method. The results showed that the
      SHG values of compounds 1, 2, and 5 are larger than that of urea. Compound 5 has
      a highest beta(CT microg) value among the 12 compounds. Although the different
      electronegativities of hydrocarbyl (R) attached to nitrogen atom should have an
      effect on the extent of intralmolecular charge-transfer and further influence
      SHG, beta(CT microg) or beta(xxx) values, the relationships between
      electronegativity of R and SHG, beta(CT microg) or beta(xxx) could not be found.
      But it is found that the bigger the donating-electron ability of R, the longer
      the maximum absorption wavelength of 10-hydrocarbylacridone molecules.

PMID- 11506023
TI  - Infrared and quantum-chemical studies of the structure and vibrations of
      trisilylamine.
AB  - New infrared spectra are reported for variously labelled trisilylamines. Quantum
      chemical (QC) calculations of structure and force field have been made at HF, MP2
      and B3LYP levels, each with the 6-31G* and 6-311G** basis sets. At each level, a
      minimum in the potential surface occurs at the C3h configuration. No evidence was
      found for a significant variation in SiH bond length with orientation. The
      appearance of two bands in the infrared spectrum of N(SiH3)3 in the 2nuSiH region
      is explained by local mode theory in terms of transitions to (200) and (110)
      levels. In the gas phase, signal averaging appears to occur in the nuSiH region
      in the infrared spectrum, but not in the Raman. In solid films, both IR and Raman
      spectra indicate the presence of a range of SiH bond strengths, corresponding to
      an absence of any site symmetry. Each complete QC calculated force field was
      fitted to the frequencies observed for N(SiH3)3 and N(SiD3)3, using nine
      independent scale factors. An interaction force constant between nu(as)NSi3 and
      delta(s)SiH3 motions required further adjustment. Unobserved frequencies in the
      d0 and d9 species are predicted. The out-of-plane skeletal bending mode is
      expected to lie between 170 and 200 cm(-1). Unscaled SiH3 torsional frequencies
      vary from 64 cm(-1) upwards. The effect of the presence of three internal rotors
      on the spectra throughout calls for theoretical study.

PMID- 11506024
TI  - Spectrofluorimetric flow injection determination of trace amounts of periodate.
AB  - A sensitive, rapid and selective procedure is proposed for the flow injection
      determinations of periodate by spectrofluorometric detection. The method is based
      on the reaction of periodate with Alizarin Navy Blue in basic solution. The
      reagents and manifold variables influence on the sensitivity have been
      investigated and the optimum conditions are established. Periodate can be
      determined for the range of 0.250-5.00 microg ml(-1) with a limit of detection of
      0.08 microg ml(-1), and with a sample rate of 15 +/- 2 samples h(-1). The
      relative standard deviations for eight replicate determination of 0.500 and 5.00
      microg ml(-1) was 1.3 and 1.1%, respectively. Periodate can be determined in the
      presence of iodate and bromate. The proposed method was used to determination of
      periodate in water samples.

PMID- 11506025
TI  - Effects of cyclodextrins on the complexation between Methylene Blue and
      tetrakis(4-sulfonatophenyl)porphyrin in aqueous solutions.
AB  - In aqueous solutions buffered at pH 10.1, Methylene Blue (MB) forms a complex
      with tetrakis(4-sulfonatophenyl)porphyrin (TSPP). The equilibrium constant for
      the formation of the MB-TSPP complex has been evaluated to be 2.35 x 10(5) mol(
      1) dm3 from the fluorescence quenching of MB by TSPP. Effects of alpha-, beta-,
      and gamma-cyclodextrin (CD), and heptakis(2,3,6-tri-O-methyl)-beta-cyclodextrin
      on the complexation between MB and TSPP have been examined by means of absorption
      and fluorescence spectroscopy. The binding of CDs to TSPP and/or MB in the MB
      TSPP complex causes the dissociation of the MB-TSPP complex.

PMID- 11506026
TI  - Spectral studies on metal-ligand bonding of novel rhodanine azodye sulphadrugs.
AB  - A series of novel complexes with 5-sulphadiazineazo-3-phenyl-2-thioxo-4
      thiazolidinone (H2L1) and 5-sulphamethazineazo-3-phenyl-2-thioxo-4-thiazolidinone
      (H2L2) and various anions were prepared. Their structures and properties were
      characterized by elemental analyses, IR, UV-vis, EPR spectroscopy and magnetic
      measurements. The visible and EPR spectral studies indicated that the Cu(II)
      complexes have distorted octahedral. From the electron paramagnetic resonance and
      spectral data, the orbital reduction factors k(parallel) and k(perpendicular)
      were calculated. In all cases k(perpendicular) > k(parallel) indicates a 2B1g
      ground state. The crystal field parameters for Co(II) and Ni(II) complexes were
      calculated. The electronic absorption and a g(parallel)/A(parallel) values are
      indicative for the beginning of tetragonal distortion. The complexes, however,
      have lower symmetries and the amount of distortion in terms of DT/Dp, applying
      NSH 'Hamiltonian Theory' has been evaluated which indicate that the complexes are
      moderately distorted.

PMID- 11506027
TI  - Mass resolved MPI spectra of methyl iodide in the 430-490 nm region.
AB  - The mass resolved multiphoton ionization (MPI) spectra of methyl iodide were
      obtained in the 430-490 nm region using a time-of-flight (TOF) mass spectrometer.
      They have the same vibrational structure, which testifies that the fragment
      species, in the wavelength region under study, are from the photodissociation of
      multiphoton ionized molecular parent ions. Some features in the spectra are
      identified as three-photon excitations to 6p and 7s Rydberg states of methyl
      iodide. Two new vibrational structures of some Rydberg states are observed. The
      mechanism of ionization and dissociation is also discussed.

PMID- 11506028
TI  - The resonance Raman effect of dicaesium uranyl tetrachloride in dimethyl
      sulfoxide.
AB  - The resonance Raman scattering spectra of dicaesium uranyl tetrachloride
      (Cs2UO2Cl4) in dimethyl sulfoxide ((CH3)2SO) have been measured under laser
      excitation of the uranyl ion in resonance with the 1sigma(g)+ --> 1phi(g) Laport
      forbidden f-f electronic transitions (520-450 nm) by using 10 output lines of the
      argon-ion laser at room temperature. The excitation profile of the totally
      symmetric stretching vibrational mode of uranyl observed at 830 cm(-1) is
      presented and analyzed in terms of the transform methods which are able to
      formally bypass multimode complexities. The non-Condon model (generalized B, C
      terms of scattering) gives a relatively good agreement with the resonance
      excitation profile of experiment. Reliable value of the nuclear displacement on
      going the 1sigma(g)+ --> 1phi(g) electronic transition and the amount of charge
      transferred from the ligand to uranium of uranyl ion both in the ground and
      excited states are obtained. It is found that the average number of ligands
      coordinated equatorically to the central uranium atom affects on the amount of
      charge transferred from the ligand to uranium, especially in the electronic
      excited state. As increasing the average number of ligands, the amount of charge
      transferred from the ligand to uranium increases in the ground state, while in
      the electronic excited state, the charge transferred decreases.

PMID- 11506029
TI  - Raman and FTIR spectroscopies of fluorescein in solutions.
AB  - Raman and Fourier transform-infra red (FT-IR) spectroscopies of fluorescein in
      aqueous solutions have been investigated in the pH range from 9.1 to 5.4. At pH
      9.1 fluorescein is in the dianion form. At pH 5.4, fluorescein is a mixture of
      monoanion (approximately 85%), dianion and neutral forms (together approximately
      15%). The fluorescence quantum yield drops from 0.93 for the dianion form to 0.37
      for the monoanion form. The Raman and FT-IR studies focused on the frequency
      range from 1000 to 1800 cm(-1) which contains the skeletal vibrational modes of
      the xanthene moiety of fluorescein. At pH 9.1, the spectroscopic feature of
      fluorescein dianion are consistent with a picture of an electron delocalized
      among the xanthene moiety and two identical oxygens attached to opposite ends of
      the xanthene moiety, forming a very symmetric structure. The characteristic of
      fluorescein dianion is the presence of the phenoxide-like stretch at 1310 cm(-1).
      At pH 5.4, fluorescein monoanion has lost the symmetric structure characteristic
      of the dianion. The spectra of the monoanion have distinctive contributions from
      the phenolic bend at 1184 cm(-1). The assignments of the vibrational bands shown
      in Raman and FT-IR spectra are given based on both literature and the ab initio
      calculations at the Hartree-Fock level with HF/6-31 + +G* basis set. Excellent
      correlation is found between the experimental and calculated spectra.

PMID- 11506030
TI  - Determination of the onset of crystallization of N1-2-(thiazolyl)sulfanilamide
      (sulfathiazole) by UV-Vis and calorimetry using an automated reaction platform;
      subsequent characterization of polymorphic forms using dispersive Raman
      spectroscopy.
AB  - This work describes the use of UV/visible spectroscopy and calorimetry to follow
      the onset of crystallization of a commercially available compound, N(1)-2
      (thiazolyl)sulfanilamide (sulfathiazole), during crystallization reactions
      performed using an automated reaction platform. Sulfathiazole has been the
      subject of numerous publications through which considerable confusion about the
      morphic form is apparent. This work does not attempt to investigate exhaustively
      the polymorph issue, but rather to exploit the use of the HEL auto-MATE for
      monitoring the onset of crystal formation. Real-time calorimetry and UV-Vis
      spectroscopy are compared as tools for determining the onset of crystallization.
      Subsequently, differential scanning calorimetry, dispersive Raman, and infrared
      spectroscopy analysis serve to identify the crystal forms generated by the HEL
      auto-MATE. A solvent-anti-solvent matrix and several bench-top crystallization
      experiments were performed to supplement the investigation in terms of generating
      the desired polymorphs.

PMID- 11506031
TI  - The role of cellulose acetate as a matrix for aggregation of pseudoisocyanine
      iodide: absorption and emission studies.
AB  - Films of pseudoisocyanine iodide in a cellulose acetate matrix were prepared by
      spin coating and characterized by UV/Vis absorption and fluorescence
      spectroscopies. The comparison with self-supported films of the same dye enabled
      analysing the role of the matrix in the aggregation of pseudoisocyanine iodide
      ([PIC]I). It was proved that cellulose acetate is a suitable support for [PIC]I J
      aggregates, which form during spinning, as shown by a very sharp J-band in the
      absorption spectra. This indicates a perfect coherence between stacked monomers
      in the supported J-aggregates. It was possible to individualize the emission
      spectrum of [PIC]I J-aggregates in cellulose acetate, by decomposition of the
      steady-state fluorescence spectra of the films. The dependence on the excitation
      wavelength of the relative emission intensities of monomers and J-aggregates, for
      lambda(em) = 587 nm, lead to confirm that the latter species have an absorption
      maximum at approximately 500 nm in cellulose acetate. Finally, polarised
      absorption spectra of films obtained by the vertical spin coating technique
      showed that cellulose acetate allows a partial orientation of J-aggregates.

PMID- 11506032
TI  - Effect of beta-cyclodextrin on the excited state proton transfer in 1-naphthol-2
      sulfonate.
AB  - The photophysical properties of 1-naphthol-2-sulfonate (1-NOH-2-S) in various
      solvents and in aqueous beta-cyclodextrin (CD) solution have been investigated.
      The fluorescence quantum yields in non-aqueous solvents are approximately 0.5,
      while in water the fluorescence quantum yield is 0.1. The fluorescence quantum
      yield doubled on the addition of beta-CD. In aqueous solution, proton transfer to
      water takes place efficiently leading to the formation of the anion form with its
      longer wavelength emission broad band at about 460 nm. Any environmental changes
      have been found to affect the rate of deprotonation and subsequently the band
      intensity at 460 nm. In non-aqueous solution the anion emission band disappears
      completely. Upon the addition of beta-CD to the aqueous solution of 1-NOH-2-S,
      the anion emission decreases with an increase in the intensity of the neutral
      form at 362 nm. Fluorescence measurements show 1:1 inclusion of 1-NOH-2-S in the
      beta-CD cavity with an association constant of 1915 M(-1) using Benesi-Heldbrand
      treatment. 1H NMR studies are used to confirm the inclusion and to provide
      information on the orientation of 1-NOH-2-S inside the cavity of beta-CD.

PMID- 11506033
TI  - The C(2)1pi(u) state of Na2 molecule studied by polarization labelling
      spectroscopy method.
AB  - The C1pi(u) <-- X1sigma(g)+ system of Na2 is studied by the polarization
      labelling spectroscopy technique. Accurate molecular constants are derived for
      the observed levels nu = 0-12, J = 12-100 in the C1pi(u) state.

PMID- 11506034
TI  - Kinetic spectrophotometric method for the determination of oxalic acid by its
      catalytic effect on the oxidation of safranine by dichromate.
AB  - A new catalytic kinetic spectrophotometric method for the determination of oxalic
      acid has been described based on its catalytic effect on the redox reaction
      between safranine and dichromate in dilute sulfuric acid media. The reaction is
      monitored photometrically by measuring the decrease in absorbance of safranine at
      the maximum wavelength of 530 nm. Under the optimum conditions, a calibration
      graph from 0.10 to 10.00 microg ml(-1) of oxalic acid with a detection limit of
      0.08 microg ml(-1) was obtained. The relative standard deviation (R.S.D.) for ten
      replicate measurements of 1.0 and 5.0 microg ml(-1) oxalic acid was 2.7 and 2.5%,
      respectively. The purposed method is simple, sensitive, selective and
      inexpensive. The applicability of the proposed method was determined by the
      determination of oxalic acid in spinach and wastewater samples with satisfactory
      results.

PMID- 11506035
TI  - Donor-donor energy migration (DDEM) as a tool for studying aggregation in lipid
      phases.
AB  - A BODIPY-labelled sulfatide (N-(BODIPY-FL-pentanoyl)-galactosylcerebroside
      sulfate, hereafter abbreviated as BD-Sulfatide) was solubilised at different
      concentrations in lipid vesicles of 1,2-dioleoyl-sn-glycero-3-phosphocholine
      (DOPC). Time-correlated single photon counting experiments show that the
      fluorescence relaxation is mono-exponential (with a lifetime of 6.5 ns) at molar
      ratios of BD-Sulfatide: DOPC that are less than 1:100. The fluorescence steady
      state anisotropy decreases monotonously at molar ratios smaller than 1:1000,
      which is compatible with donor-donor energy migration (DDEM) among the BODIPY
      groups. A model that assumes DDEM across the lipid bilayers, as well as in their
      planes, was used to analyse the time-resolved fluorescence anisotropy. Only two
      parameters appear in the model namely: the bilayer thickness (d) and the average
      number density (C2) distribution of BD-Sulfatide in the lipid bilayers. The
      extracted d-values vary between 35 and 40 A, which is about the reported
      thickness of a bilayer of DOPC (38 A). Hence, the BODIPY groups are
      preferentially located in the water-lipid interface. At low concentration the
      experimental C2-values and those independently calculated are in good agreement,
      while the experimental values gradually become lower with increasing BD-Sulfatide
      concentration. These results are compatible with an aggregation of the sulfatides
      and self-quenching of BODIPY, which is clearly established at higher
      concentrations of the BD-Sulfatide.

PMID- 11506036
TI  - Spectral studies of semicarbazones derived from 3- and 4-formylpyridine and 3-
      and 4-acetylpyridine: crystal and molecular structure of 3-formylpyridine
      semicarbazone.
AB  - Semicarbazones derived from 3- and 4-formylpyridine (H3FoPyS, H4FoPyS) and 3- and
      4-acetylpyridine (H3AcPyS, H4AcPyS) were prepared and studied spectroscopically.
      Complete NMR assignments for these semicarbazones were made using DEPT135, as
      well as HMQC and HMBC heteronuclear correlation techniques. The crystal and
      molecular structures of H3FoPyS were determined.

PMID- 11506037
TI  - Balloon-borne near-infrared diode laser spectroscopy for in situ measurements of
      atmospheric CH4 and H2O.
AB  - Absorption spectroscopy with near-infrared telecommunication laser diodes is a
      very convenient technique to measure in situ methane and water vapor in both the
      troposphere and the lower stratosphere (LS) and thereby to address many topics in
      the science of the atmosphere. This technique offers a high temporal resolution
      that ranges from 10 ms to 1 s, a precision error in the concentration retrieval
      of within a few percents and a dynamic range for the measurements of four orders
      of magnitude. A balloon-borne near-infrared diode laser spectrometer is described
      that provides simultaneous in situ methane (in the 1.65-microm region) and water
      vapor (in the 1.39-microm region) measurements at 1 s intervals. Tropospheric and
      stratospheric vertical concentration profiles of methane and water vapor are
      reported.

PMID- 11506038
TI  - Self-association of rhodamine dyes in different host materials.
AB  - The aggregation of rhodamine 6G in liquid crystalline solution (anisotropic host)
      was studied using polarised spectroscopy and in a guest-host system. The self
      association of rhodamine B was investigated in molecular sieves of type AlPO(4)-5
      (microporous host) using diffuse reflectance spectroscopy. Also, the molecular
      interaction of rhodamines in normal solvents (isotropic hosts) was studied using
      visible spectroscopy for comparison. Therefore, the role of the host nature in
      the different phases on the self-association of the guest molecules has been
      investigated and compared. The absorption spectrum of the rhodamine dye in liquid
      crystalline host is affected by a specific interaction related to the alignment
      by the liquid crystal property as well as solvent polarity. Due to the existence
      of a large amount of water molecules absorbed into channels and cavities of
      aluminophosphate molecular sieve, the maximum absorption wavelengths of the dye
      loaded AlPO(4)-5 is affected by aqueous environment of the aluminophosphate
      pores.

PMID- 11506039
TI  - Large edge-excitation red-shift of the fluorescence of an ethanol solution of 1
      (4'-amino-biphenyl-4-yl)-ethanone (ABE).
AB  - The photophysics of 1-(4'-amino-biphenyl-4-yl)-ethanone (ABE) is reported. The
      observed large edge-excitation-red-shift of the fluorescence of ABE in a rigid
      ethanol medium and the red shift of the absorption band as the temperature is
      lowered are interpreted in terms of a microscopic solvent heterogeneity.

PMID- 11506040
TI  - Study of the preferential solvation of some betaine dyes in binary solvent
      mixtures.
AB  - The preferential solvation (PS) in mixed binary solvents, e.g.
      dichloromethane/acetonitrile, dichloromethane/methanol, acetonitrile/water has
      been studied by monitoring the charge transfer band of some betaine dyes. Since
      PS accounts for dielectric as well as specific interactions while dielectric
      enrichment only for the former, it was shown that in the case of
      dichloromethane/methanol, hydrogen bonding precedes dielectric enrichment whereas
      in the case of acetonitrile/water the inverse is true.

PMID- 11506041
TI  - Electron spin resonance studies and theoretical quantum calculations of free
      radicals generated from anthracenetrione by electrochemical and microsomal
      reduction.
AB  - The ESR spectra of radicals obtained by electrolytic reduction of 4,4
      dimethylanthracene-1,9,10 (4H)-trione (1) and the regioisomeric quinones 8
      acetyloxymethyl-4,4,5-trimethyl- (2), and 5-acetyloxy-methyl-4,4,8-trimethyl-(4H)
      1,9,10-anthracenetrione (3) were measured in DMSO and analyzed by quantum
      chemical calculations. The electrochemistry of these compounds was characterized
      using cyclic voltammetry, in DMSO and DMF solvents and compared with nifurtimox.
      The quinones were also reduced by microsomal NADPH-cytochrome P-450 reductase and
      the corresponding radicals species were also detected by ESR spectroscopy. AMI,
      INDO, and ADF calculations were performed to obtain the optimized geometries,
      theoretical hyperfine constants, and spin distributions, respectively. Density
      functional theory was used to rationalize the reduction potential of these
      compounds.

PMID- 11506042
TI  - Spectral-luminescent study of the porphyrin-diketones and their complexes.
AB  - Syntheses of octaethylporphine-diketone (OEPDK) and its platinum(II) and
      palladium(II) complexes (PtOEPDK, PdOEPDK) were optimized, and the dyes were
      isolated in a pure form in preparative quantities. They were characterized by the
      NMR, UV-VIS absorption and emission spectroscopy. Electronic spectra of these
      dyes (absorption and luminescence) were investigated in detail, and compared to
      corresponding porphyrins and porphyrin-monoketones. OEPDK showed a strong
      fluorescence at about 700 nm, while PtOEPDK and PdOEPDK showed very weak room
      temperature phosphorescence in the region of 850-1100 nm and practically no
      fluorescence. Protonation mechanisms were studied for these dyes. Protonation at
      sites other than pyrrole nitrogen atoms was shown to occur, corresponding
      protomeric spectral forms are presented. The possibilities of the use of
      porphyrin-diketones as longwave fluorescent and phosphorescent probes are
      discussed.

PMID- 11506043
TI  - Multivariate evaluation of doxorubicin surface-enhanced Raman spectra.
AB  - Multivariate evaluation of surface-enhanced Raman spectra of doxorubicin in
      plasma was performed. In a principal component analysis (PCA) all spectral
      features were modelled into three principal components. The major variation of
      the data was shown to be the variation of doxorubicin Raman signal together with
      the doxorubicin fluorescence, whereas the variation due to plasma was of minor
      importance. It was also shown that the surface-enhanced Raman scattering (SERS)
      measurements were independent on such factors as measurement occasion and silver
      colloids. The presented results show that with some improvements, quantification
      of doxorubicin directly in plasma could be possible.

PMID- 11506044
TI  - Self-effacing wit as a response to oppression: dynamics in ethnic humor.
AB  - Theories of self-effacing ethnic humor are analyzed from the perspectives of
      psychological defense and acculturation. These processes are contrasted with
      masochism as explanations of self-directed wit. Developmental paradigms are
      appealed to in conceptualizing the sociocultural function of humor.
      Identification with the aggressor is conceptualized as a transitional mechanism
      to assimilate the minority into the host culture. Turning against the self is
      developed as an alternate mechanism that uses humor as a means of self
      empowerment. Reframing and splitting are posited as integral to the defensive
      process of ethnic humor. The method of luring the aggressor into a situation that
      is then used against him is construed as the kamikaze maneuver and conceptualized
      as an ambush technique in which the role of self-effacement facilitates
      aggression. The analytic elements of these approaches are explored with reference
      to Jewish humor as a stereotype of the wit of a transient and oppressed people,
      and annotated examples are offered from published anthologies. Illustrative
      vignettes, ranging from the mundane to the clinical, are annotated in the
      discussion. Directions for further inquiry are outlined for issues unresolved in
      the research literature.

PMID- 11506045
TI  - Singaporean humor: a cross-cultural, cross-gender comparison.
AB  - One hundred and nineteen undergraduate students (62 men and 57 women) of Chinese
      origin at the National University of Singapore answered three self-report humor
      questionnaires. Students were also asked to supply their favorite joke (M. A.
      Johnson, 1991) and a description of a person with an outstanding sense of humor
      (M. Crawford & D. Gressley, 1991). These responses were compared with results
      obtained using the same questionnaires and methods in previous studies in Israel
      and the United States. In general, means and reliabilities of results obtained
      from the Singapore study replicated those found in other countries. However,
      Singaporean participants reported significantly less use of humor for coping.
      Content analysis of jokes supplied by Singaporean students reflected conservative
      values: Compared with American students, they reported a significantly greater
      number of jokes with aggressive content and relatively fewer jokes with sexual
      content. Contrary to expectations, very few gender differences were found.
      Regardless of gender, a majority of participants nominated a man as an example of
      a person with an outstanding sense of humor.

PMID- 11506046
TI  - Contextual connections to puns in fables: perceived humor.
AB  - Adding material that provided an associative connection to a pun enhances
      perceived humor, as shown in a previous series of studies. Because those results
      had been based on one-sentence statements that may have relied, in part, on
      brevity for humor, the purpose of the present study was to evaluate reactions to
      context and puns (mostly spoonerisms) with more lengthy material to add
      generality to those findings. Three within-subject studies were conducted in
      which short fables were manipulated systematically such that the final sentence
      was or was not a pun and contextual information pertaining to both meanings of
      the pun was or was not present in the body of the stories. Results showed that
      the pun itself was a powerful contributor to perceived humor and cleverness and
      that contextual information amplified those perceptions. Arousal, surprise, and
      detection of appropriate incongruity are discussed.

PMID- 11506047
TI  - Humor in therapy: the case for training therapists in its uses and risks.
AB  - Formal humor training for therapists is proposed as an elective part of their
      academic curriculum. The paucity of rigorous empirical research on the
      effectiveness of this historically controversial form of clinical intervention is
      exceeded only by the absence of any training for those practitioners interested
      in applying humor techniques. A representative sample of its many advocates'
      recommendations to incorporate humor in the practice of psychological therapies
      is reviewed. Therapeutic humor is defined, the role of therapists' personal
      qualities is discussed, and possible reasons for the profession's past resistance
      to promoting humor in therapy are described. Research perspectives for the
      evaluation of humor training are presented with illustrative examples of
      important empirical questions. In addition to its potential salubrious effects on
      clients, therapeutic humor might have the positive side effect of preventing or
      minimizing professional burnout in therapists. This potentially major
      psychotherapeutic resource, highly praised by some, remains insufficiently
      evaluated and essentially untapped.

PMID- 11506048
TI  - Does humor in radio advertising affect recognition of novel product brand names?
AB  - The authors proposed that item selection during shopping is based on brand name
      recognition rather than recall. College students rated advertisements and news
      stories of a simulated radio program for level of amusement (orienting activity)
      before participating in a surprise recognition test. Humor level of the
      advertisements was varied systematically, and content was controlled. According
      to signal detection analysis, humor did not affect the strength of recognition
      memory for brand names (nonsense units). However, brand names and product types
      were significantly more likely to be associated when appearing in humorous
      advertisements than in nonhumorous advertisements. The results are compared with
      prior findings concerning humor and recall.

PMID- 11506049
TI  - The effectiveness of humor in persuasion: the case of business ethics training.
AB  - In this study, persuasion theory was used to develop the following predictions
      about use of humor in persuasive messages for business ethics training: (a)
      cartoon drawings will enhance persuasion by creating liking for the source, (b)
      ironic wisecracks will enhance persuasion by serving as a distraction from
      counterarguments, and (c) self-effacing humor will enhance persuasion by
      improving source credibility. Canadian business students (N = 148) participated
      in 1 of 4 versions of "The Ethics Challenge," a training exercise used by the
      Lockheed Martin Corporation. Three versions were modified by adding or removing
      cartoon drawings (of cartoon characters Dilbert and Dogbert) and humorous
      responses (Dogbert's wisecracks). Removing the cartoon drawings had little effect
      on persuasiveness. Removing ironic wisecracks had more effect, and interfering
      with the self-effacing combination of cartoons and wisecracks had the strongest
      effect. The results suggest that researchers should ground their predictions in
      existing theory and that practitioners should differentiate among humor types.

PMID- 11506050
TI  - The effects of laughter on discomfort thresholds: does expectation become
      reality?
AB  - Distraction and relaxation have been controlled in previous studies as possible
      mechanisms for the effectiveness of mirthful laughter in coping with pain and
      discomfort. The purpose of this study is to control expectation of benefit from
      laughter. Discomfort thresholds for a blood pressure cuff at the upper dominant
      arm were recorded immediately before and after exposure to either a humorous or a
      relaxation video. Instructional sets led participants to believe that the video
      would either increase or decrease their sensitivity to discomfort. A 5th group
      watched the humorous video without manipulation of expectation. All participants
      completed A. Ziv's (1979) Sense of Humor Questionnaire (SHQZ). Humor and
      relaxation videos raised discomfort thresholds, and the effect of both video
      types was enhanced by expectations. Humorous personality trait (SHQZ) did not
      moderate effects. The larger issue of whether mirthful laughter has any unique
      benefit for pain or discomfort control beyond the effects of relaxation,
      distraction, or expectation is discussed.

PMID- 11506051
TI  - Sociality effects on the production of laughter.
AB  - Certain facial displays (typically the human smile) have been found to vary with
      a situation's sociality. Because the facial display that accompanies laughter is
      under less voluntary control, it is a stronger test of sociality effects.
      Participants (N = 162) were videotaped watching a humorous videoclip in 1 of 3
      conditions: alone, in a same-sex dyad with a stranger, or in a same-sex dyad with
      a friend. The frequency and time spent laughing were significantly greater in one
      or both dyadic conditions than in the alone condition, although no differences
      existed for self-reported evaluations of the videoclip's funniness or amusement
      felt. When the self-report measures were controlled for, the dyads of strangers
      (compared with the alone condition) were associated with the frequency of
      laughter. Although the results provide further support for sociality effects, the
      situational demands faced by participants may be a better predictor of facial
      displays than level of sociality.

PMID- 11506052
TI  - Using humor in systematic desensitization to reduce fear.
AB  - Effectiveness of systematic desensitization for fear reduction, using humorous
      hierarchy scenes without relaxation, was tested. Participants were 40 students
      highly fearful of spiders. Using a 24-item behavioral approach test with an
      American tarantula, participants were matched on fear level and randomly assigned
      to 1 of 3 treatment groups: (a) systematic desensitization, (b) humor
      desensitization, and (c) untreated controls. Each participant was seen for 6
      sessions, including pretest and posttest. Analyses of covariance of posttest
      scores revealed that the 2 treatment groups showed greater reduction in fear than
      the controls on 3 measures but did not differ from each other. Therefore, humor
      in systematic desensitization reduced fear as effectively as more traditional
      desensitization. This finding may have therapeutic applications; however, it may
      also be applicable in advertising to desensitize fear of a dangerous product,
      such as cigarettes.

PMID- 11506053
TI  - Controversy over dietary phosphorus.

PMID- 11506054
TI  - The institute of medicine's "dietary reference intake" for phosphorus: a critical
      perspective.
AB  - Two questions relevant to the safety of phosphate additives have been raised in
      the literature: 1) Is the dietary ratio of calcium to phosphorus clinically
      significant in humans? Specifically, can a high-phosphorus, low-calcium diet
      cause hypocalcemia and/or secondary hyperparathyroidism in humans? 2) Does the
      growing use of phosphate-containing food additives increase the risk of low bone
      density and/or fracture in humans? In 1999, the Institute of Medicine published a
      monograph which addressed these two questions. This article critically reviews
      the findings and conclusions of the Institute of Medicine in the light of recent
      research.

PMID- 11506055
TI  - Effects of dietary arabinogalactan on gastrointestinal and blood parameters in
      healthy human subjects.
AB  - OBJECTIVES: Arabinogalactan (AG) is a non-digestible soluble dietary fiber that
      resists hydrolytic enzyme action and enters the large bowel intact where it is
      fermented by resident microflora. To determine whether AG has similar
      physiological properties to other soluble dietary fibers, we examined the effect
      of 15 and 30 g per day of a commercially available AG from Western Larch on
      several gastrointestinal and blood parameters. METHODS: Gastrointestinal
      parameters included fecal microflora, fecal enzyme activity, fecal short-chain
      fatty acids, fecal pH, fecal weight, transit time and bowel frequency. Blood
      parameters included total cholesterol, HDL cholesterol, LDL cholesterol,
      triglycerides, Apo-A1, Apo-B, glucose and insulin. The study consisted of two
      three-week diet treatments with no washout period. Participants (n=20, 11 males,
      9 females) consumed their usual diet in addition to 15 or 30 g AG in a beverage
      sweetened with aspartame as compared to their usual diet with the control
      beverage. RESULTS: Significant increases in total fecal anaerobes were observed
      with 15 g (p=0.01) and 30 g AG (p=0.001). A significant increase (p=0.02) in
      Lactobacillus spp. was observed when subjects consumed AG for a total of six
      weeks regardless of dose. There were no significant changes in other microflora,
      fecal enzyme activity, transit time, frequency, fecal weight, fecal pH and short
      chain fatty acids. Fecal ammonia levels decreased with 15 g (p=0.001) and 30 g
      (p=0.002) AG. No significant changes in blood lipids or blood insulin were
      observed. CONCLUSIONS: These data suggest that dietary AG is easily incorporated
      into the diet, well tolerated in subjects and has some positive effects on fecal
      chemistry.

PMID- 11506056
TI  - Iron absorption during recovery from malnutrition.
AB  - OBJECTIVE: In infants and children recovering from severe malnutrition, iron
      deficiency is common, and the ability to absorb iron during such recovery is
      uncertain. The objective of this study was to determine iron absorption during
      recovery from malnutrition. METHODS: During the later stages of recovery from
      malnutrition, erythrocyte incorporation of orally administered 58Fe was
      determined as a surrogate for iron absorption. Based on four indices, subjects
      were classified as iron-sufficient, iron-deficient or indeterminate. RESULTS: Of
      the 25 subjects, 9 were classified as iron sufficient, 5 as indeterminate and 11
      as iron deficient; all but 5 had evidence of inflammation or infection. Geometric
      mean erythrocyte incorporation of 58Fe was 32.0% of the dose in the iron
      deficient subjects, which was not significantly different (p = 0.073) than the
      13.1% in the iron-sufficient subjects. Incorporation of 58Fe by the iron
      sufficient subjects did not differ significantly from that by normal subjects in
      the same age range. Surprisingly, we found no correlation of erythrocyte
      incorporation of 58Fe and reticulocyte count. CONCLUSIONS: Even in the presence
      of infection or inflammation, iron absorption by children during a late stage of
      recovery from malnutrition is not impaired.

PMID- 11506057
TI  - Effect of chromium supplementation and exercise on body composition, resting
      metabolic rate and selected biochemical parameters in moderately obese women
      following an exercise program.
AB  - OBJECTIVE: To investigate the effect of chromium picolinate (CP) supplementation
      on body composition, resting metabolic rate (RMR), selected biochemical
      parameters and iron and zinc status in moderately obese women participating in a
      12-week exercise program. METHODS: Forty-four women, 27 to 51 years of age, were
      randomly assigned to two groups based on their body mass index. Subjects received
      either 400 microg/day of chromium as a CP supplement or a placebo in double-blind
      fashion and participated in a supervised weight-training and walking program two
      days per week for 12 weeks. Body composition and RMR were measured at baseline, 6
      and 12 weeks. Selected biochemical parameters and iron and zinc status were
      measured at baseline and 12 weeks. RESULTS: Body composition and RMR were not
      significantly changed by CP supplementation. No significant differences in
      fasting plasma glucose, serum insulin, plasma glucagon, serum C-peptide and serum
      lipid concentrations or in iron and zinc indices were found between the two
      groups over time. Serum total cholesterol concentration significantly decreased
      (p = 0.0016) over time for all subjects combined, probably as a result of the
      exercise training. Exercise training significantly reduced total iron binding
      capacity (TIBC) by 3% for all subjects combined (p = 0.001 1). CONCLUSIONS:
      Twelve weeks of 400 microg/day of chromium as a CP supplement did not
      significantly affect body composition, RMR, plasma glucose, serum insulin, plasma
      glucagon, serum C-peptide and serum lipid concentrations or iron and zinc indices
      in moderately obese women placed on an exercise program. The changes in serum
      total cholesterol levels and TIBC were a result of the exercise program.

PMID- 11506058
TI  - Safety and tolerability of esterified phytosterols administered in reduced-fat
      spread and salad dressing to healthy adult men and women.
AB  - OBJECTIVE/DESIGN: The safety and tolerability of three levels of plant sterol
      esters administered in reduced-fat spread and salad dressing vs. control products
      were evaluated in this randomized, double-blind, four-arm parallel study.
      METHODS: Eighty-four free-living men and women consumed reduced-fat spread and
      salad dressing providing 0.0 g/day (n = 21), 3.0 g/day (n = 21), 6.0 g/day (n =
      19) or 9.0 g/day (n = 23) of phytosterols as esters for an eight-week treatment
      period. RESULTS: Side effects did not differ among the groups during the study,
      and there were no study product-related serious adverse events. There were no
      changes in clinical laboratory values in response to phytosterol intake. Blood
      concentrations of all fat-soluble vitamins remained within normal reference
      ranges, and there were no differences in serum vitamin responses among the four
      groups. Alpha- and trans-beta-carotene levels were reduced in the 9.0 g/day group
      vs. control (p < 0.05), but all carotenoid values remained within normal ranges
      throughout the study. All groups receiving phytosterols had significant increases
      in serum campesterol vs. control (p < 0.001), but beta-sitosterol responses did
      not differ from control. Total, low-density lipoprotein (LDL) and high-density
      lipoprotein (HDL) cholesterol responses did not differ significantly among the
      groups. The total:HDL cholesterol response in the 9.0 g/day group was
      significantly different from the control group response (-9.6% vs. 2.6%, p <
      0.05). A median increase of 7.8% in serum triglycerides was observed in the
      control group, which differed significantly from the response in the 3.0 g/day
      arm (-13.3%, p < 0.05). DISCUSSION: The results of this study indicate that
      phytosterol esters are well tolerated and show no evidence of adverse effects at
      a daily intake of up to 9.0 g of phytosterols for eight weeks.

PMID- 11506059
TI  - Effects of monounsaturated enriched sunflower oil on CHD risk factors including
      LDL size and copper-induced LDL oxidation.
AB  - OBJECTIVE: To compare the effects of a diet high in monounsaturated enriched
      sunflower oil and a low fat diet on CHD risk factors including in vitro Cu
      induced LDL oxidation and LDL size, lipids, lipoproteins, glucose and insulin.
      DESIGN: A randomized crossover dietary intervention. SETTING: Free living
      individuals. SUBJECTS: Fourteen healthy males 35 to 55 years of age and 14
      healthy postmenopausal women 50 to 60 years of age completed the dietary
      intervention. Two subjects did not complete the study, and their data were not
      included. INTERVENTIONS: A low fat, high carbohydrate diet (22% to 25% of energy
      from total fat, 7% to 8% of energy from monounsaturated fat and 55% to 60% of
      energy from carbohydrate) was compared to a monounsatutated enriched sunflower
      oil (MO) diet (40% to 42% of energy from fat, with 26% to 28% from
      monounsaturated fat and 40% to 45% of energy from carbohydrate) in an isocaloric
      substitution. Each dietary period was one month. RESULTS: Total cholesterol, LDL
      cholesterol, triglycerides and glucose were not significantly different between
      the two diets. HDL cholesterol, HDL3 cholesterol and insulin were significantly
      higher on the MO diet, mean 7%, 7% and 17% higher respectively. Copper-induced
      LDL oxidation lag phase was significantly longer (mean 18%) after the MO diet
      compared to the low fat, high carbohydrate diet. LDL particle size was not
      significantly different. CONCLUSIONS: The significant increase in LDL oxidation
      lag phase and the significantly higher HDL cholesterol on the MO diet would be
      expected to be associated with a decrease in CHD risk.

PMID- 11506060
TI  - A hydroxychalcone derived from cinnamon functions as a mimetic for insulin in 3T3
      L1 adipocytes.
AB  - OBJECTIVES: These studies investigated the ability of a hydroxychalcone from
      cinnamon to function as an insulin mimetic in 3T3-LI adipocytes. METHODS:
      Comparative experiments were performed with the cinnamon methylhydroxychalcone
      polymer and insulin with regard to glucose uptake, glycogen synthesis.
      phosphatidylinositol-3-kinase dependency, glycogen synthase activation and
      glycogen synthase kinase-3beta activity. The phosphorylation state of the insulin
      receptor was also investigated. RESULTS: MHCP treatment stimulated glucose uptake
      and glycogen synthesis to a similar level as insulin. Glycogen synthesis was
      inhibited by both wortmannin and LY294002, inhibitors directed against the PI-3
      kinase. In addition, MHCP treatment activated glycogen synthase and inhibited
      glycogen synthase kinase-3beta activities, known effects of insulin treatment.
      Analysis of the insulin receptor demonstrated that the receptor was
      phosphorylated upon exposure to the MHCP. This supports that the insulin cascade
      was triggered by MHCP. Along with comparing MHCP to insulin, experiments were
      done with MHCP and insulin combined. The responses observed using the dual
      treatment were greater than additive, indicating synergism between the two
      compounds. CONCLUSION: Together, these results demonstrate that the MHCP is an
      effective mimetic of insulin. MHCP may be useful in the treatment of insulin
      resistance and in the study of the pathways leading to glucose utilization in
      cells.

PMID- 11506061
TI  - Dietary and supplement treatment of iron deficiency results in improvements in
      general health and fatigue in Australian women of childbearing age.
AB  - OBJECTIVE: To examine the effects of iron deficiency and its treatment by iron
      supplementation or a high iron diet on fatigue and general health measures in
      women of childbearing age. DESIGN: Randomised controlled trial to compare
      supplement and dietary treatment of iron deficiency. SUBJECTS: 44 iron deficient
      (serum ferritin < 15 microg/L or serum ferritin 15-20 microg/L, plus two of the
      following: serum iron < 10 micromol/L, total iron binding capacity > 68
      micromol/L or transferrin saturation < 15%) and 22 iron replete (hemoglobin > or
      = 10 g/L and serum ferritin > 20 microg/L) women 18 to 50 years of age were
      matched for age and parity. INTERVENTIONS: Iron deficient women were randomly
      allocated to either iron supplementation or a high iron diet for 12 weeks.
      MEASURES OF OUTCOME: Iron deficient and iron replete participants had iron
      studies performed and completed the Piper Fatigue Scale (PFS) and the SF-36
      general health and well-being questionnaire at baseline (T0), following the 12
      week intervention (T1) and again after a six-month non-intervention phase (T2).
      The SF-36 includes measures of physical (PCS) and mental (MCS) health and
      vitality (VT). RESULTS: MCS and VT scores were lower and PFS scores were higher
      for iron deficient women (diet and supplement groups) than iron replete women at
      baseline. Both intervention groups showed similar improvements in MCS, VT and PFS
      scores during the intervention phase, but mean increases in serum ferritin were
      greater in the supplement than the diet group. PCS scores were not related to
      iron status. CONCLUSIONS: Treatment of iron deficiency with either
      supplementation or a high iron diet results in improved mental health and
      decreased fatigue among women of childbearing age.

PMID- 11506062
TI  - Influence of skin maceration and oxygen on anaerobic fermentation of grape musts
      with high sugar content.
AB  - Saccharomyces cerevisiae race cerevisiae was used to ferment grape musts in
      strictly anaerobic conditions, subjected to a prefermentative treatment of skin
      maceration and following a short aeration after 48 h of fermentation. Skin
      maceration caused an increase in the cellular phospholipid content which affected
      neither viability nor the fermentative capacity of the yeasts. The short aeration
      had no significant effect on the unsaturation index of the cellular fatty acids,
      although it did increase the ergosterol/phospholipid ratio. This was reflected by
      an increase in the growth rate, viability and fermentative capacity of the
      yeasts. Maceration did not increase the effect of aeration.

PMID- 11506063
TI  - Neutrophil apoptotic cell death: does it contribute to the increased infectious
      risk in aging?
AB  - During the last few years, several studies have pointed out the imbalance of
      immune response with advancing age, which accounts for the increased
      susceptibility of elderly individuals to life-threatening diseases. This review
      is focused on the role of neutrophil apoptosis in the age-associated decline of
      cytotoxicity towards invading micro-organisms. The results indicate that the
      overall intrinsic mechanisms regulating neutrophil cell death are unaffected by
      age. Neutrophils from aged humans exhibit a diminished ability to be rescued by
      proinflammatory mediators, as well as a weak buffer capacity towards proapoptotic
      reactive oxygen species (ROS) generated during cell stimulation. Such events may
      hamper in vivo the accumulation of functionally active cells in inflammatory
      areas, thus contributing to the increased infection-related risk of morbidity and
      mortality with advanced age. The impact of these new findings in terms of
      therapeutic applications is discussed.

PMID- 11506064
TI  - HIV-1 multi-dideoxynucleoside resistance mutation (Q151M): prevalence, associated
      resistance mutations and response to antiretroviral salvage treatment.
AB  - The prevalence and clinical implications of the Q151M multidrug-resistance
      mutation gene (mut) to antiretroviral drugs in the HIV reverse transcriptase (RT)
      gene have not yet been fully explained. In the present study three out of 350
      (0.85%) of HIV-infected patients who underwent a drug-resistance genotyping assay
      because of therapeutic failure showed the Q151M mut. All these patients had been
      previously treated with zidovudine in association with didanosine. One such
      patient failed to respond to all salvage regimens tried and was shown to harbour
      some of the characteristic mut associated with Q151M (77L and 116Y). Another two
      patients partially responded to salvage regimens, both virologically and
      immunologically, and harboured the M184V mut in the RT gene. The prevalence of
      Q151M mut in our group was less (0.85%) than in other studies, which ranged from
      2 to 19%. The M184V mut seemed to confer some viro-immunological benefit when
      associated with the Q151M mutation, compared with the latter alone.

PMID- 11506065
TI  - Toxicity of two carbamate insecticides to the cyanobacterium Anabaena PCC 7120
      and computations of partial lethal concentrations by the probit method.
AB  - Toxicity studies of two commercial carbamate insecticides, carbaryl and
      carbofuran with the nitrogen-fixing filamentous cyanobacterium Anabaena PCC 7120,
      are described. Under nitrogen-fixing conditions and with calcium nitrate
      supplementation, 100 and 120 ppm carbaryl were the respective lethal
      concentrations (LC100), while 20 to 80 ppm (nitrogen-fixing conditions) and 20 to
      100 ppm (with nitrate supplementation) were the partial lethal doses (<LC100).
      Under nitrogen-fixing conditions and nitrate supplementation, 100 to 1,000 ppm
      and 100 to 1,200 ppm were the respective partial lethal concentrations, whereas
      1,500 ppm carbofuran was the LC100 for both conditions. In agar media, the
      highest permissive insecticide concentrations were 60 ppm for carbaryl and 250
      ppm for carbofuran; minimum inhibitory concentrations were 10 and 25 ppm; and the
      LC100 were 80 and 300 ppm, respectively. Computations of percentage lethal data
      yielded LC25, LC50 and LC75 values by the probit method. The number of vegetative
      cells between two successive heterocysts decreased. The N-content of the cultures
      in nitrogen-fixing medium determined by the micro-Kjeldahl method, was affected
      significantly by both insecticides. Carbofuran was less hazardous than carbaryl
      to the cyanobacterium.

PMID- 11506066
TI  - Changes in fatty acid composition of Pseudomonas aeruginosa ATCC 15442 induced by
      growth conditions: consequences of resistance to quaternary ammonium compounds.
AB  - The effects of changes in the fatty acid composition of Pseudomonas aeruginosa
      induced by growth conditions on its resistance to two quaternary ammonium
      compounds (QAC) were investigated. The temperature and growth phase were the most
      influential parameters affecting the fatty acid composition of this bacterium.
      Furthermore, the formation of saturated fatty acids and cyclopropane fatty acids
      was stimulated by increasing the temperature, whereas the proportion of
      unsaturated fatty acids fell. The degree of saturation and the proportion of
      cyclopropane fatty acids increased in the course of the exponential and
      stationary phases. These modifications mostly concerned the inner membrane of the
      bacterium. Resistance of P. aeruginosa to both QAC tested was not significantly
      influenced by temperature and growth phase variations. Thus, resistance to the
      two QAC did not seem to be dependent on modifications of the fatty acid
      composition of the inner membrane.

PMID- 11506067
TI  - Asian American acculturation and ethnic/racial identity: research innovations in
      the new millennium--introduction to the special issue.
AB  - Research on Asian American acculturation and ethnic/racial identity, although
      still in development, has evolved and progressed over the past few decades.
      Researchers are now developing and using more complex and advanced methods of
      examining these issues in a culturally and ethnically heterogeneous population.
      Indeed, this special issue of Cultural Diversity and Ethnic Minority Psychology
      demonstrates the diverse state-of-the-art research in this area. The coeditors of
      the special issue highlight themes and specific contributions to the literature
      for each article.

PMID- 11506068
TI  - The Korean diasporic experience: measuring ethnic identity in the United States
      and China.
AB  - The measurement and development of ethnic identity of Koreans living in the
      United States and China were examined in the context of different migration
      experiences. Three hundred sixteen undergraduate college students were
      administered the Multigroup Ethnic Identity Measure (MEIM; J. S. Phinney, 1992).
      Separate principal-component analysis for each sample was performed to create
      cross-culturally equivalent Ethnic Identity and Other-Group subscales.
      Differential item function analysis revealed no cultural item bias among the
      retained MEIM items. Korean Americans had higher scores on the Ethnic Identity
      and Other-Group subscales and were more likely to be classified as bicultural
      than were Korean Chinese. Korean Chinese were more likely to be classified as
      assimilated, traditional, or marginalized in their cultural orientation.

PMID- 11506069
TI  - Racial identity and reflected appraisals as influences on Asian Americans' racial
      adjustment.
AB  - J. E. Helms's (1990) racial identity psychodiagnostic model was used to examine
      the contribution of racial identity schemas and reflected appraisals to the
      development of healthy racial adjustment of Asian American university students (N
      = 188). Racial adjustment was operationally defined as collective self-esteem and
      awareness of anti-Asian racism. Multiple regression analyses suggested that
      racial identity schemas and reflected appraisals were significantly predictive of
      Asian Americans' racial adjustment. Implications for counseling and future
      research are discussed.

PMID- 11506070
TI  - Unidimensional versus multidimensional approaches to the assessment of
      acculturation for Asian American populations.
AB  - This study used generational status and the Suinn-Lew Asian Self-Identity
      Acculturation scale to examine unidimensional versus multidimensional approaches
      to the conceptualization and measurement of acculturation and their relationships
      to relevant cultural indicator variables, including measures of Individualism
      Collectivism, Independent-Interdependent Self-Construal, Loss of Face, and
      Impression Management. Multivariate analyses of covariance and partial
      correlations were used to examine the relationship between the acculturation
      models and each set of cultural indicator variables while controlling for
      socioeconomic status. Given that acculturation differences are often cited as
      evidence for a culture effect between groups, the present findings of an uneven
      nature of these relationships as a function of the particular acculturation
      measurement strategy have important implications for research on Asian Americans.

PMID- 11506071
TI  - Holding on and letting go: identity and acculturation among Chinese immigrants.
AB  - This study addresses the general question of whether ethnic identity and general
      acculturation would prove unique discriminators of quality of life for Chinese
      immigrants. Eighty-three Chinese immigrants served as participants. Survey data
      were collected regarding acculturation, Asian identity, and quality of life;
      observers provided ratings of certain home environment characteristics; and
      participants responded to open-ended interview questions about their immigration
      experiences that allowed for qualitative data analysis on perspectives of
      culture. Significant analysis of covariance and post hoc comparison results
      revealed meaningful main effects and interactions between acculturation and Asian
      identity in explaining the immigrants' quality of life and ecocultural aspects of
      their home environments. Interview responses illuminated important distinctions
      between groups distinguished by level of acculturation and ethnic identity.
      Findings are discussed in terms of methodological and conceptual issues in
      studying acculturation and ethnic identity in immigration experiences and
      practical implications for immigrants and those working with them.

PMID- 11506072
TI  - The role of acculturation in the career adjustment of Asian American workers: a
      test of Leong and Chou's (1994) formulations.
AB  - F.T.L. Leong and E.L. Chou (1994) provided a theoretical model for understanding
      the acculturation process among Asian Americans and applied that model to
      predicting the potential career adjustment problems encountered by Asians in the
      United States. Several of the hypotheses proposed by Leong and Chou were
      empirically tested in 2 separate studies. In Study 1, acculturation (R.M. Suinn,
      K. Rickard-Figueroa, S. Lew, & P. Vigil, 1987) was found to be positively related
      to job satisfaction (A.H. Brayfield & H.F. Rothe, 1951) and negatively related to
      occupational stress and strain (S. H. Osipow & A.R. Spokane, 1981) in a sample of
      39 Asian American employees from 2 major companies who attended career
      development workshops. In Study 2, acculturation was found to be positively
      related to supervisors' performance ratings in a different sample of 27 Asian
      American employees. These preliminary data suggest that acculturation plays an
      important role in the career development of Asian Americans. The theoretical,
      research, and counseling implications of the findings are discussed.

PMID- 11506073
TI  - Design and development of the European American values scale for Asian Americans.
AB  - Existing instruments for measuring Asian American acculturation emphasize
      behavior acculturation to the exclusion of value acculturation. Most are based on
      the assumption that acquisition of European American behavior occurs
      simultaneously with the loss of Asian behavior. With the advent of the Asian
      Values Scale (AVS; B.S.K. Kim, D.R. Atkinson, & P.H. Yang, 1999), it is now
      possible to assess adherence to Asian cultural values. This article describes the
      development of a scale that can be used to measure Asian American adherence to
      European American values. The current scale, combined with the AVS, can be used
      to independently measure Asian American acculturation to European American values
      and enculturation in Asian values.

PMID- 11506074
TI  - Cultural predictors of self-esteem: a study of Chinese American female and male
      young adults.
AB  - This study examined how specific domains of cultural orientation (language,
      social affiliation, and cultural pride) related to self-esteem for a sample of
      174 Chinese American male and 179 Chinese American female college students.
      Participants completed measures of cultural orientation (General Ethnicity
      Questionnaire; J.L. Tsai, Y.W. Ying, & P.A. Lee, 2000) and self-esteem (M.
      Rosenberg, 1965). Cultural orientation significantly predicted self-esteem, above
      and beyond the contribution of age, gender, grade point average, and
      socioeconomic status. Specifically, proficiency in English and Chinese languages
      and pride in Chinese culture were positively correlated with self-esteem, whereas
      affiliation with Chinese people was negatively correlated with selfesteem. The
      cultural predictors of self-esteem differed for Chinese American men and women.
      Whereas self-esteem was mainly related to pride in Chinese culture for Chinese
      American women, self-esteem was mainly related to English and Chinese language
      proficiency for Chinese American men. Implications of these findings for
      understanding Asian Americans are discussed.

PMID- 11506075
TI  - Stress and pregnancy loss: role of immune mediators, hormones and
      neurotransmitters.
AB  - This review highlights recent studies investigating the impact of stress on
      pregnancy health or loss. Spontaneous abortion is the most common adverse
      pregnancy outcome, and stress has been suggested to be abortogenic in mice and
      humans. A wealth of information has been published on the effect of stress on the
      nervous, endocrine and immune systems during the past two decades. Stress- and/or
      pregnancy-related hormones (corticotropin releasing hormone, adrenocorticotropin,
      prolactin, and progesterone) might interact with peripheral and local
      immuncompetent cells, such as certain T cell subsets, mast cells or NK cells, and
      result in changes of cytokine production. Since a well-balanced interaction of
      nervous, endocrine and immune system is crucial for the maintenance of successful
      pregnancy, putative mechanisms and recent observations on stress-triggered
      pregnancy failure have been reviewed.

PMID- 11506076
TI  - Thrombophilic gene mutations and recurrent spontaneous abortion: prothrombin
      mutation increases the risk in the first trimester.
AB  - PROBLEM: Thrombophilic predisposition may be one of the underlying causes of
      recurrent spontaneous abortions (RSA). We studied the prevalence of five
      thrombophilic gene mutations in patients with RSA. METHOD OF STUDY: 102 patients
      with two or more consecutive abortions and 128 women without miscarriage were
      analyzed for factor V Leiden mutation (FVL), prothrombin G20210A mutation (PTM),
      C677T mutation in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene,
      glycoprotein IIIa (GPIIIa) C1565T polymorphism, and beta-fibrinogen G-455A
      polymorphism by polymerase chain reaction (PCR) techniques. RESULTS: No
      differences in the prevalence of FVL, MTHFR T/T, GPIIIa and 1-fibrinogen
      polymorphism were detected. Heterozygous PTM occurred more often in patients with
      RSA. This effect was significant in a subgroup with abortions exclusively in the
      first trimester (6.7%, vs. 0.8%, P = 0.027, OR 8.5). CONCLUSIONS: In contrast to
      the other mutations and polymorphisms, heterozygous PTM is more common in
      patients with abortions in the first trimester. This might reflect an influence
      of PTM on pathogenesis of early pregnancy loss.

PMID- 11506077
TI  - High NK cell activity in early pregnancy correlates with subsequent abortion with
      normal chromosomes in women with recurrent abortion.
AB  - PROBLEM: The aim of this study was to assess the role of natural killer (NK)
      cells in pregnant women with a history of recurrent spontaneous abortion (RSA).
      METHOD OF STUDY: Consecutive 66 pregnant women with a history of RSA were
      prospectively assessed for peripheral NK cell activity, percentage of the NK cell
      subsets, and subsequent pregnancy outcome. RESULTS: NK cell activity in women
      with subsequent live birth (group I) at 4-5 gestational weeks (GW) (mean +/- SD,
      32.5 +/- 12.31%) significantly decreased at 6-7 GW (28.1 +/- 12.1%) and at 8 9 GW
      (28.0 +/- 11.8%). NK cell activity in women with subsequent abortion with normal
      chromosomes (group II) at 6 7 GW (41.2 +/- 19.0%) was significantly higher than
      that in group I women, while NK cell activity at 6-7 GW in women with subsequent
      abortion with abnormal chromosomes (group III) was the same as the level in group
      I women. CONCLUSIONS: High NK cell activity at 6-7 GW correlates with subsequent
      abortion with normal chromosomes.

PMID- 11506078
TI  - Choriocarcinoma cells modulate the cytokine production of decidual large granular
      lymphocytes in coculture.
AB  - PROBLEM: How do major histocompatibility complex (MHC) I positive/negative
      choriocarcinoma (CC) cells affect the production of tumor necrosis factor-alpha
      (TNF-alpha), interferon-gamma (IFN-gamma), interleukin-10 (IL-10), interleukin-4
      (IL-4), and granulocyte-macrophage colony-stimulating factor (GM-CSF) by decidual
      CD56++ cells (large granular lymphocytes [LGL]), LGL-depleted decidual cells
      (WASH) and unseparated decidual cells (DEC) in cocultures? METHOD OF STUDY:
      Decidual tissue was obtained by legal abortions. CD 56++ LGL were isolated in a
      magnetic cell separator. Cytokines were measured by ELISA. Differences were
      analyzed for significance by Wilcoxons test. RESULTS: We found a significant
      increase of IL-10 in LGL/JEG-3 and of TNF-alpha in LGL/JAR cocultures compared to
      noncocultured decidual cells. There was a significant increase of IL-10 and TNF
      alpha and a significant decrease of GM-CSF in WASH and DEC cocultures with both
      JEG-3 and JAR. IFN-gamma was only found in 3/11 cases of LGL/JAR cocultures. No
      IL-4 was found in any experiment. CONCLUSION: MHC class I positive/negative CC
      modulate the cytokine production of decidual LGL in different ways.

PMID- 11506079
TI  - Expression of decay accelerating factor in endometrial adenocarcinoma is
      inversely related to the stage of tumor.
AB  - PROBLEM: Decay accelerating factor (DAF) is implicated in protection of cell
      membrane from toxicity of complement. In this study, we investigated a hypothesis
      that DAF is up-regulated in the endometrial adenocarcinoma, which could increase
      potential of malignant cells to escape destruction by complement. METHODS: DAF
      density was evaluated in endometrial biopsies of patients with adenocarcinoma at
      various stages and compared with ten endometrial biopsies from non-malignant
      patients at the proliferative phase. RESULTS: DAF expression in normal
      proliferative endometrium varied between 1 and 30%. While DAF density in patients
      with stage I cancer was in the range 56-98% (mean 78%), stage III values varied
      from 28 to 16% (mean 21%), P < 0.05. DAF density in the well-differentiated
      Ishikawa cell line was two-fold higher than in metastatic cell line AN3CA.
      CONCLUSIONS: Our findings are consistent with a hypothesis that endometrial
      adenocarcinoma of early stage that is exposed to complement attack may up
      regulate DAF to protect malignant cells from complement lysis.

PMID- 11506080
TI  - Isolation of antibody to human placental alkaline phosphatase (PLAP) from
      extracts of human placentae.
AB  - PROBLEM: Human placental alkaline phosphatase (PLAP) is a unique placental
      antigen bound to the syncytiotrophoblast, which may be able to elicit a specific
      immune response in pregnancy. METHOD OF STUDY: Antibody to PLAP was purified from
      placental extracts by: a) acid elution of membrane vesicles; b) purifying
      complexes of PLAP with human antibody on monoclonal antibodies to PLAP followed
      by denaturation of the enzyme; and c) by denaturation of PLAP in placental
      extracts and purification of antibody to PLAP on PLAP columns. RESULTS AND
      CONCLUSIONS: Specific antibody to PLAP is present in placental extracts, and is
      mostly bound to placental membrane preparations. PLAP is therefore immunogenic in
      pregnancy and could serve as a useful monitor of pregnancy-specific immunological
      responses. Since a similar enzyme appears in some cancers, it is possible that
      the immunization against PLAP in pregnancy will help to protect against the
      development of ovarian and endometrial cancer (the 'fetal antigen' hypothesis).

PMID- 11506081
TI  - Expression of tumor necrosis factor-alpha in the pregnant uterus of diabetic
      mice: effect of maternal immunopotentiation.
AB  - PROBLEM: Tumor necrosis factor (TNF)-alpha mRNA and protein are expressed in the
      pregnant uterus of streptozotocin-induced diabetic mice at various stages of
      pregnancy. We intend to characterize their pattern and to evaluate whether the
      potentiation of the maternal immune system alters the pattern of the expression
      of the cytokine. METHOD OF STUDY: Diabetes was induced in ICR mice by
      streptozotocin injection. To modulate maternal immune responses, ICR mice were
      injected intrauterine with rat splenocytes 3 weeks before mating. The expression
      of TNF-alpha mRNA and protein was evaluated by in situ hybridization and
      immunohistochemistry techniques. RESULTS: The population of diabetic mice used in
      this study demonstrated a reduction in pregnancy rate and an increased number of
      litters with severely malformed fetuses. It has been observed that these
      disturbances are associated with a clear increase in TNF-alpha mRNA and protein
      expression in the uterus of these mice. Maternal immunopotentiation, while
      improving reproductive performance of these diabetic mice, was found to be
      accompanied by a reduced expression of TNF-alpha, both at the mRNA and protein
      level. CONCLUSIONS: The results of the present study suggest a possible
      involvement of TNF-alpha in mechanisms underlying diabetes-associated
      dismorphogenesis. Normalization of TNF-alpha expression by maternal
      immunopotentiation might represent a mechanism mediating its protective effect
      against diabetes-induced embryotoxic insult.

PMID- 11506082
TI  - Comparative T-cell responses during pregnancy in large animals and humans.
AB  - PROBLEM: Placentation in different large animal species shows a remarkable
      diversity in the level of trophoblast invasion into the maternal endometrial
      tissues. We wish to determine the influence of implantation on T-cell responses
      during pregnancy. METHOD OF STUDY: Review of the literature and current data.
      RESULTS: alphabeta-TCR+ T cells are only prominent during early pregnancy in
      species with relatively non-invasive placentation (pig and horse) but are rapidly
      downregulated in species with more invasive placentae. gammadelta-TCR+ T cells
      are prominent in species with moderate trophoblast invasion (ruminants) where
      they increase dramatically during mid and late pregnancy. gammadelta-TCR+ T cells
      remain prominent during late gestation in species with highly invasive
      placentation (humans) and, in addition, a distinct gammadelta T-cell population
      is present in first trimester decidua where it may play a regulatory role in
      controlling natural killer cell activity. The gammadelta-TCR+ population present
      in both ruminants and humans shows large granular morphology and contains
      antimicrobial proteins, suggesting their function may be to protect the uterine
      environment from infection during pregnancy and parturition. CONCLUSION: The
      comparative analysis of T-cell responses during pregnancy in different large
      animal species supports an increasing role for cells of the innate immune
      response (NK and gammadelta T cells) and a downregulation of the adaptive immune
      response with increasingly invasive placentation.

PMID- 11506083
TI  - Technology update.
AB  - The history of diagnostic US is marked by a remarkable series of giant advances
      in technology that have had major impact on the clinical impact of sonography. As
      the twenty-first century begins, US is poised for additional major advances in
      performance and clinical impact. In the evaluation of a multitude of diseases
      these developments will bring improvements in screening, diagnosis, and
      management and extend the value of US to a greatly expanded population.

PMID- 11506084
TI  - Ultrasound contrast agents: a promising future.
AB  - The emerging field of contrast ultrasound has great and untapped potential.
      Improved vascular enhancement may increase the number and type of diagnostic
      vascular examinations. Improved vessel depiction may increase examination speed
      and improve patient throughput. New gray-scale contrast imaging techniques may
      substantially increase the sonographic detection and characterization of liver,
      kidney, and other focal parenchymal masses. Contrast ultrasound examinations may
      increase diagnostic confidence, decrease nondiagnostic studies, and decrease the
      requirement for additional imaging studies. Further investigation is needed,
      however, to determine the diagnostic use and cost-effectiveness of this new
      approach relative to CT, MR imaging, angiography, and conventional ultrasound
      imaging.

PMID- 11506085
TI  - Ultrasound-guided intervention: expanding horizons.
AB  - Ultrasound-guided intervention has enjoyed a period of unprecedented growth
      because its many advantages over other guidance modalities have been recognized.
      The decreased procedure time, increased accuracy, and safety of procedures
      performed under ultrasound guidance are of obvious benefit to radiologist and
      patient alike for all interventional applications. Lesions once considered unsafe
      to sample are now reasonably approached with ultrasound guidance. As equipment
      technology continues to improve and radiologists increasingly recognize the
      benefits of guiding procedures with ultrasound, the shift of procedures away from
      CT and fluoroscopic guidance will continue and ultrasound guidance will become
      the guidance method of choice for most interventional procedures.

PMID- 11506086
TI  - Intraoperative ultrasound.
AB  - Intraoperative ultrasound is an exciting arena for real-time depiction and
      evaluation of relevant anatomy and pathology. The information provided by this
      technique often is pivotal to the surgeon, and not infrequently impacts the
      nature and extent of the surgical procedure. As more radiologists develop an
      interest and become facile with IOUS, and as more surgeons appreciate the
      benefits of this modality, the numbers and applications for this technique will
      continue to expand. This, coupled with continued commercial and technical
      improvements, and increasing demand for minimally invasive surgery, ensures that
      the future of IOUS will be a bright one.

PMID- 11506087
TI  - Current status of diagnostic and therapeutic endoscopic ultrasonography.
AB  - Endoscopic ultrasonography is firmly established as an imaging modality that can
      be used for diagnosing and staging both malignant and nonmalignant disorders of
      the pancreas, gastrointestinal tract, biliary tree, and mediastinum. In the
      future, as more physicians are trained and as technologic developments continue
      to advance, endosonography will likely assume a greater role in therapeutic
      management.

PMID- 11506088
TI  - Musculoskeletal ultrasound: an update.
AB  - In summary, musculoskeletal sonography is a rapidly growing field of interest
      around the world. Outside of America, it is often the first and definitive
      imaging modality fordisorders of the musculoskeletal system. Musculoskeletal
      ultrasound offers rapid, inexpensive, real-time examination of the structures of
      interest with easy comparison to the contralateral side. Principles of one area
      of musculoskeletal sonography easily generalize to other areas.

PMID- 11506089
TI  - Breast ultrasound.
AB  - Ultrasound is second in importance only to mammography in the evaluation of
      breast abnormalities. The ability of US to diagnose benign simple cysts
      accurately has spared innumerable women from needless biopsies and aspirations.
      When a suspicious solid abnormality is detected by ultrasound, it readily
      provides convenient, inexpensive, accurate imaging guidance for interventional
      procedures. Future studies of US as a screening tool must weigh potential
      benefits against the potential risks because of increased biopsies performed for
      false-positive results.

PMID- 11506090
TI  - Three-dimensional ultrasound in obstetrics and gynecology.
AB  - Three-dimensional ultrasound is a new modality finding its way into clinical
      practice. Most of the major ultrasound vendors are now developing three
      dimensional ultrasound capabilities. We expect that although three-dimensional
      ultrasound will not replace two-dimensional ultrasound, many additional benefits
      will be identified and its use will continue to grow. The ability to evaluate
      anatomy and pathology with multiplanar and surface-rendered images provides
      physicians additional valuable clinical information. Volume data allows for a
      specific point in space to be evaluated from many different orienta tions by
      rotating, slicing, and referencing the slice to other orthogonal slices. It also
      allows for new volume-rendering displays that show depth, curvature, and surface
      images not available with conventional methods. The current limitations of image
      resolution, intuitive interfaces for obtaining and displaying optimal images, and
      technologic limitations for data storage and manipulation (including real-time
      three-dimensional ultrasound) will surely be overcome in the near future.

PMID- 11506091
TI  - Gynecologic ultrasound.
AB  - For most women, pelvic sonography using a transvaginal probe is the imaging
      modality of choice for evaluating the uterus and adnexae. It is reliable for
      detecting ovarian cysts and other adnexal masses, and it can often determine if a
      lesion can be observed on serial examinations or if it requires more urgent
      attention. Uterine ultrasound is reliable for evaluating both the normal and
      abnormal endometrium and myometrium. In cases that are technically limited, or in
      those that are difficult to interpret, a tailored MR imaging examination often
      can be helpful.

PMID- 11506092
TI  - Sonographic assessment of posthemorrhagic ventricular dilatation.
AB  - Sonography plays a key role in the initial evaluation and monitoring of
      ventricular dilatation in the newborn. The use of supplemental imaging approaches
      by the mastoid fontanelle and foramen magnum can help identify the cause and
      location of obstruction. Duplex Doppler of intracranial vessels during anterior
      fontanelle compression is a useful indicator of altered cranial compliance in
      these infants. Additional views of the thoracolumbar spine can help identify
      which infants will likely benefit from lumbar puncture for therapy of progressive
      ventricular dilatation.

PMID- 11506093
TI  - Current approach to peripheral arterial sonography.
AB  - Color and pulsed Doppler imaging have assumed a prominent role for evaluating
      noninvasively lower-extremity arterial occlusive disease. In conjunction with
      indirect arterial tests, ultrasound imaging is recommended to screen for lower
      extremity disease. It provides not only specific information regarding location,
      severity, and frequency of disease, but it can also determine the optimal
      therapeutic approach before more invasive procedures. Using ultrasound for graft
      surveillance is mandatory for identifying flow-reducing lesions that may lead to
      subsequent bypass failure. As new developments become perfected and clinically
      available, ultrasound contrast agents, three-dimensional imaging, and B-flow
      imaging each seem to have great potential for assessing peripheral arterial
      disease. In all likelihood, these additions will further improve the diagnostic
      capability of ultrasound and may also lead to the development of new vascular
      applications for this modality.

PMID- 11506094
TI  - Carotid ultrasound.
AB  - This article provides an overview of basic diagnostic carotid ultrasound
      applications, and emphasizes practical aspects of this examination. Areas
      currently being investigated include carotid plaque characterization and
      applications relative to IMT measurements. Contrast-enhanced ultrasound imaging
      also offers promise to improve plaque characterization, which in turn may link
      these evaluations to outcome studies.

PMID- 11506095
TI  - Pharmacokinetic-pharmacodynamic modeling and ICU sedation: unexplored
      territories.

PMID- 11506096
TI  - The upper respiratory tract infection (URI) dilemma: fear of a complication or
      litigation?

PMID- 11506097
TI  - A double-blind, randomized comparison of i.v. lorazepam versus midazolam for
      sedation of ICU patients via a pharmacologic model.
AB  - BACKGROUND: Benzodiazepines, such as lorazepam and midazolam, are frequently
      administered to surgical intensive care unit (ICU) patients for postoperative
      sedation. To date, the pharmacology of lorazepam in critically ill patients has
      not been described. The aim of the current study was to characterize and compare
      the pharmacokinetics and pharmacodynamics of lorazepam and midazolam administered
      as continuous intravenous infusions for postoperative sedation of surgical ICU
      patients. METHODS: With Institutional Review Board approval, 24 consenting adult
      surgical patients were given either lorazepam or midazolam in a double-blind
      fashion (together with either intravenous fentanyl or epidural morphine for
      analgesia) through target-controlled intravenous infusions titrated to maintain a
      moderate level of sedation for 12-72 h postoperatively. Moderate sedation was
      defined as a Ramsay Sedation Scale score of 3 or 4. Sedation scores were
      measured, together with benzodiazepine plasma concentrations. Population
      pharmacokinetic and pharmacodynamic parameters were estimated using nonlinear
      mixed-effects modeling. RESULTS: A two-compartment model best described the
      pharmacokinetics of both lorazepam and midazolam. The pharmacodynamic model
      predicted depth of sedation for both midazolam and lorazepam with 76% accuracy.
      The estimated sedative potency of lorazepam was twice that of midazolam. The
      predicted C50,ss (plasma benzodiazepine concentrations where P(Sedation > or =
      ss) = 50%) values for midazolam (sedation score [SS] > or = n, where n = a Ramsay
      Sedation Score of 2, 3, ... 6) were 68, 101, 208, 304, and 375 ng/ml. The
      corresponding predicted C50,ss values for lorazepam were 34, 51, 104, 152, and
      188 ng/ml, respectively. Age, fentanyl administration, and the resolving effects
      of surgery and anesthesia were significant covariates of benzodiazepine sedation.
      The relative amnestic potency of lorazepam to midazolam was 4 (observed). The
      predicted emergence times from sedation after a 72-h benzodiazepine infusion for
      light (SS = 3) and deep (SS = 5) sedation in a typical patient were 3.6 and 14.9
      h for midazolam infusions and 11.9 and 31.1 h for lorazepam infusions,
      respectively. CONCLUSIONS: The pharmacology of intravenous infusions of lorazepam
      differs significantly from that of midazolam in critically ill patients. This
      results in significant delays in emergence from sedation with lorazepam as
      compared with midazolam when administered for ICU sedation.

PMID- 11506098
TI  - Risk factors for perioperative adverse respiratory events in children with upper
      respiratory tract infections.
AB  - BACKGROUND: Anesthesia for the child who presents for surgery with an upper
      respiratory infection (URI) presents a challenge for the anesthesiologist. The
      Current prospective study was designed to determine the incidence of and risk
      factors for adverse respiratory events in children with URTs undergoing elective
      surgical procedures. METHODS: The study population included 1,078 children aged 1
      month to 18 yr who presented for an elective surgical procedure. Parents were
      given a short questionnaire detailing their child's demographics, medical
      history, and presence of any symptoms of a URT. Data regarding the incidence and
      severity of perioperative respiratory events were collected prospectively.
      Adverse respiratory events (any episode of laryngospasm, bronchospasm, breath
      holding > 15 s, oxygen saturation < 90%, or severe cough) were recorded. In
      addition, parents were contacted 1 and 7 days after surgery to determine the
      child's postoperative course. RESULTS: There were no differences between children
      with active URIs, recent URIs (within 4 weeks), and asymptomatic children with
      respect to the incidences of laryngospasm and bronchospasm. However, children
      with active and recent URIs had significantly more episodes of breath holding,
      major desaturation (oxygen saturation < 90%) events, and a greater incidence of
      overall adverse respiratory events than children with no URIs. Independent risk
      factors for adverse respiratory events in children with active URIs included use
      of an endotracheal tube (< 5 yr of age), history of prematurity, history of
      reactive airway disease, paternal smoking, surgery involving the airway, the
      presence of copious secretions, and nasal congestion. Although children with URIs
      had a greater incidence of adverse respiratory events, none were associated with
      any long-term adverse sequelae. CONCLUSIONS: The current study identified several
      risk factors for perioperative adverse respiratory events in children with lulls.
      Although children with acute and recent URIs are at greater risk for respiratory
      complications, these results suggest that most of these children can undergo
      elective procedures without significant increase in adverse anesthetic outcomes.

PMID- 11506099
TI  - Comparison of metaraminol and ephedrine infusions for maintaining arterial
      pressure during spinal anesthesia for elective cesarean section.
AB  - BACKGROUND: Although ephedrine is usually recommended as the first-line
      vasopressor in obstetrics, its superiority over other vasopressors has not been
      proven in humans. METHODS: In a double-blind study, the authors randomized women
      having elective cesarean section with spinal anesthesia to receive an intravenous
      infusion of ephedrine, starting at 5 mg/min (n = 25), or metaraminol, starting at
      0.25 mg/min (n = 25), titrated to maintain systolic arterial pressure in the
      target range 90-100% of baseline. Umbilical cord gases, maternal hemodynamics,
      uterine artery puLsatility index, and Apgar scores were compared. RESULTS:
      Systolic arterial pressure was maintained more closely in the target range in the
      metaraminol group compared with the ephedrine group. In the metaraminol group,
      umbilical arterial pH was greater (median and interquartile range, 7.31 and 7.31
      7.33 vs. 7.24 and 7.14-7.29; P < 0.0001), and umbilical venous pH was greater
      (7.36 and 7.35-7.38 vs. 7.33 and 7.26-7.34; P < 0.0001) compared with the
      ephedrine group. No patient in the metaraminol group had umbilical arterial pH
      less than 7.2, compared with nine patients (39%) in the ephedrine group (P =
      0.0005). Apgar scores were similar between groups. Changes in uterine artery
      pulsatility index were similar between groups. CONCLUSIONS: When used by infusion
      to maintain arterial pressure during spinal anesthesia for cesarean section,
      metaraminol was associated with less neonatal acidosis and more closely
      controlled titration of arterial pressure compared with ephedrine.

PMID- 11506100
TI  - Concentration-effect relationship of cisatracurium at three different dose levels
      in the anesthetized patient.
AB  - BACKGROUND: The linearity of cisatracurium elimination and its concentration
      effect relation were determined as part of a traditional rich data study with
      three dose levels in patients receiving balanced anesthesia. METHODS: Forty-eight
      adults with American Society of Anesthesiologists status I-II were randomized to
      receive an intravenous bolus dose of 0.075, 0.15, or 0.30 mg/kg cisatracurium.
      Anesthesia was induced and maintained with nitrous oxide-oxygen, propofol, and
      fentanyl. The mechanical response of the adductor pollicis muscle was recorded.
      Arterial blood samples were collected over 8 h. Cisatracurium, laudanosine, and
      the monoquaternary alcohol concentrations were measured by high-performance
      liquid chromatography. To assess the relative contribution of the input function,
      a parametric (assuming elimination from both the central and peripheral
      compartments) and a nonparametric pharmacokinetic-pharmacodynamic model were both
      applied to data. RESULTS: Dose proportionality of the body disposition of
      cisatracurium and its two major metabolites at doses up to 0.30 mg/kg was
      confirmed. With the parametric approach, the effect compartment concentration at
      50% block (EC50) significantly increased with the dose (136 vs. 157 vs. 209
      ng/ml), whereas the effect compartment equilibration rate constant decreased
      (0.0675 vs. 0.0568 vs. 0.0478 min(-1)). A similar dose-dependent effect of the
      pharmacokinetic-pharmacodynamic relation was observed with the nonparametric
      approach, but the trend was 50% less pronounced. CONCLUSION: A dose-related
      change in pharmacokinetic-pharmacodynamic parameters was identified with both
      modeling approaches. A pharmacokinetic origin was ruled out, although no definite
      explanation of the underlying mechanism could be provided. These findings suggest
      that doses relevant to the anesthetic practice be used for estimation of EC50.

PMID- 11506101
TI  - Propofol dosing regimens for ICU sedation based upon an integrated
      pharmacokinetic-pharmacodynamic model.
AB  - BACKGROUND: The pharmacology of propofol infusions administered for long-term
      sedation of intensive care unit (ICU) patients has not been fully characterized.
      The aim of the study was to develop propofol dosing guidelines for ICU sedation
      based on an integrated pharmacokinetic-pharmacodynamic model of propofol
      infusions in ICU patients. METHODS: With Institutional Review Board approval, 30
      adult male medical and surgical ICU patients were given target-controlled
      infusions of propofol for sedation, adjusted to maintain a Ramsay sedation scale
      score of 2-5. Propofol administration in the first 20 subjects was based on a
      previously derived pharmacokinetic model for propofol. The last 10 subjects were
      given propofol based on a pharmacokinetic model derived from the first 20
      subjects. Plasma propofol concentrations were measured, together with sedation
      score. Population pharmacokinetic and pharmacodynamic parameters were estimated
      by means of nonlinear regression analysis in the first 20 subjects, then
      prospectively tested in the last 10 subjects. An integrated pharmacokinetic
      pharmacodynamic model was used to construct dosing regimens for light and deep
      sedation with propofol in ICU patients. RESULTS: The pharmacokinetics of propofol
      were described by a three-compartment model with lean body mass and fat body mass
      as covariates. The pharmacodynamics of propofol were described by a sigmoid
      model, relating the probability of sedation to plasma propofol concentration. The
      pharmacodynamic model for propofol predicted light and deep levels of sedation
      with 73% accuracy. Plasma propofol concentrations corresponding to the
      probability modes for sedation scores of 2, 3, 4, and 5 were 0.25, 0.6, 1.0, and
      2.0 microg/ml. Predicted emergence times in a typical subject after 24 h, 72 h, 7
      days, and 14 days of light sedation (sedation score = 3 --> 2) with propofol were
      13, 34, 198, and 203 min, respectively. Corresponding emergence times from deep
      sedation (sedation score = 5 --> 2) with propofol were 25, 59, 71, and 74 h.
      CONCLUSIONS: Emergence time from sedation with propofol in ICU patients varies
      with the depth of sedation, the duration of sedation, and the patient's body
      habitus. Maintaining a light level of sedation ensures a rapid emergence from
      sedation with long-term propofol administration.

PMID- 11506102
TI  - Effectiveness of epidural blood patch in the management of post-dural puncture
      headache.
AB  - BACKGROUND: Lumbar epidural blood patch (EBP) is a common treatment of post-dural
      puncture headache, but its effectiveness and mode of action remain a matter of
      debate. The aim of this study was to assess both the effectiveness and the
      predictive factors of failure of EBP on severe post-dural puncture headache.
      METHODS: This prospective observational study includes all patients treated in
      the authors' hospital with EBP for incapacitating post-dural puncture headache,
      from 1988 to 2000. The EBP effect was classified into complete relief
      (disappearance of all symptoms), incomplete relief of symptoms (clinically
      improved patients who recovered sufficiently to perform normal daily activity),
      and failure (persistence of severe symptoms). The following data were analyzed
      using a logistic regression to identify predictive factors of failure of EBP: (1)
      patient characteristics; (2) circumstances of dural puncture; (3) delay between
      dural puncture and EBP; and (4) the volume of blood injected for EBP. RESULTS: A
      total of 504 patients were analyzed. The frequency rates of complete relief,
      incomplete relief of symptoms, and failure after EBP were 75% (n = 377), 18% (n =
      93), and 7% (n = 34), respectively. In a multivariate analysis, only the diameter
      of the needle used to perform dura mater puncture (odds ratio = 5.96; 95%
      confidence interval, 2.63-13.47; P < 0.001) and a delay in EBP less than 4 days
      (odds ratio = 2.63; 95% confidence interval, 1.06-6.51; P = 0.037) were
      independent significant risk factors for a failure of EBP. CONCLUSIONS: Epidural
      blood patch is an effective treatment of severe post-dural puncture headache. Its
      effectiveness is decreased if dura mater puncture is caused by a large bore
      needle.

PMID- 11506103
TI  - Venous air embolism during endoscopic strip craniectomy for repair of
      craniosynostosis in infants.
AB  - BACKGROUND: Various studies have reported an incidence of venous air embolism
      (VAE) as high as 82.6% during surgical procedures for craniosynostosis. There has
      been an increase in the use of minimally invasive, endoseopie surgical
      procedures, including applications for endoscopic strip craniectomy. The current
      study prospectively evaluated the incidence of VAF during endoscopic strip
      craniectomy. METHODS: Continuous, intraoperative monitoring for VAE was performed
      using precordial Doppler monitoring. A recording was made of the Doppler tones
      and later reviewed to verify its accuracy. RESULTS: The cohort for the study
      included 50 consecutive neonates and infants ranging in age from 3.5 to 36 weeks
      and ranging in weight from 3 to 9 kg. Surgical time varied from 31 to 95 min for
      a total of 2,701 mm of operating time, during which precordial Doppler tones were
      auscultated. In 46 patients, there was no evidence of VAE. In four patients,
      there was a single episode of VAE. Two of the episodes of VAE were grade I
      (change in Doppler tones), and two were grade H (change in Doppler tones and
      decrease in end-tidal carbon dioxide). No grade III (decrease in systolic blood
      pressure by 20% from baseline) VAF was noted. CONCLUSION: In addition to
      previously reported benefits of decreased blood loss, decreased surgical time,
      and improved postoperative recovery time, the authors noted a low incidence of
      VAF during endoscopic strip craniectomy in neonates and infants.

PMID- 11506104
TI  - Fiberoptic orotracheal intubation on anesthetized patients: do manipulation
      skills learned on a simple model transfer into the operating room?
AB  - BACKGROUND: With increasing pressure to use operating room time efficiently,
      opportunities for residents to learn fiberoptic orotracheal intubation in the
      operating room have declined. The purpose of this study was to determine whether
      fiberoptic orotracheal intubation skills learned outside the operating room on a
      simple model could be transferred into the clinical setting. METHODS: First-year
      anesthesiology residents and first- and second-year internal medicine residents
      were recruited. Subjects were randomized to a didactic-teaching-only group (n =
      12) or a model-training group (n = 12). The didactic-teaching group received a
      detailed lecture from an expert bronchoscopist. The model-training group was
      guided, by experts, through tasks performed on a simple model designed to refine
      fiberoptic manipulation skills. After the training session, subjects performed a
      fiberoptic orotracheal intubation on healthy, consenting, anesthetized, paralyzed
      female patients undergoing elective surgery with predicted "easy" laryngoscopic
      intubations. Two blinded anesthesiologists evaluated each subject. RESULTS: After
      the training session, the model group significantly outperformed the didactic
      group in the operating room when evaluated with a global rating scale (P <
      0.01)and checklist (P0.05). Model-trained subjects completed the fiberoptic
      orotracheal intubation significantly faster than didactic-trained subjects (P <
      0.01). Model-trained subjects were also more successful at achieving tracheal
      intubation than the didactic group (P < 0.005). CONCLUSION: Fiberoptic
      orotracheal intubation skills training on a simple model is more effective than
      conventional didactic instruction for transfer to the clinical setting.
      Incorporating an extraoperative model into the training of fiberoptic orotracheal
      intubation may greatly reduce the time and pressures that accompany teaching this
      skill in the operating room.

PMID- 11506105
TI  - Preoperative intradermal acupuncture reduces postoperative pain, nausea and
      vomiting, analgesic requirement, and sympathoadrenal responses.
AB  - BACKGROUND: In a controlled and double-blind study, the authors tested the
      hypothesis that preoperative insertion of intradermal needles at acupoints 2.5 cm
      from the spinal vertebrae (bladder meridian) provide satisfactory postoperative
      analgesia. METHODS: The authors enrolled patients scheduled for elective upper
      and lower abdominal surgery. Before anesthesia, patients undergoing each type of
      surgery were randomly assigned to one of two groups: acupuncture (n = 50 and n =
      39 for upper and lower abdominal surgery, respectively) or control (n = 48 and n
      = 38 for upper and lower abdominal surgery, respectively). In the acupuncture
      group, intradermal needles were inserted to the left and right of bladder
      meridian 18-24 and 20-26 in upper and lower abdominal surgery before induction of
      anesthesia, respectively. Postoperative analgesia was maintained with epidural
      morphine and bolus doses of intravenous morphine. Consumption of intravenous
      morphine was recorded. Incisional pain at rest and during coughing and deep
      visceral pain were recorded during recovery and for 4 days thereafter on a four
      point verbal rating scale. We also evaluated time-dependent changes in plasma
      concentrations of cortisol and catecholamines. RESULTS: Starting from the
      recovery room, intradermal acupuncture increased the fraction of patients with
      good pain relief as compared with the control (P < 0.05). Consumption of
      supplemental intravenous morphine was reduced 50%, and the incidence of
      postoperative nausea was reduced 20-30% in the acupuncture patients who had
      undergone either upper or lower abdominal surgery (P < 0.01). Plasma cortisol and
      epinephrine concentrations were reduced 30-50% in the acupuncture group during
      recovery and on the first postoperative day (P < 0.01). CONCLUSION: Preoperative
      insertion of intradermal needles reduces postoperative pain, the analgesic
      requirement, and opioid-related side effects after both upper and lower abdominal
      surgery. Acupuncture analgesia also reduces the activation of the sympathoadrenal
      system that normally accompanies surgery.

PMID- 11506106
TI  - Effects of desflurane and sevoflurane on length-dependent regulation of
      myocardial function in coronary surgery patients.
AB  - BACKGROUND: Desflurane and sevoflurane have negative inotropic effects. The
      current study investigated whether these effects resulted in an altered left
      ventricular response to increased cardiac load and affected length-dependent
      regulation of myocardial function. Length-dependent regulation of myocardial
      function refers to the ability of the heart to improve its performance when
      preload is increased. METHODS: A high-fidelity pressure catheter was positioned
      in the left ventricle and left atrium in 20 coronary surgery patients with a
      preoperative ejection fraction greater than 40%. Studies were performed before
      the initiation of cardiopulmonary bypass. Left ventricular response to increased
      cardiac load, obtained by leg elevation, was assessed during control conditions
      and during increasing concentrations of desflurane (2, 4, and 6% end tidal; n =
      10) or sevoflurane (1, 2, and 3% end tidal; n = 10). Effects on contraction were
      evaluated by analysis of changes in maximal rate of pressure development. Effects
      on relaxation were assessed by analysis of changes in minimum rate of pressure
      development and by analysis of the load dependence of myocardial relaxation (R =
      slope of the relation between time constant tau of isovolumic relaxation and end
      systolic pressure). Peak left atrial-left ventricular pressure gradients were
      analyzed during early left ventricular filling. RESULTS: With both desflurane and
      sevoflurane, maximal and minimum rates of pressure development decreased while
      tau increased. Peak left atrial-left ventricular pressure gradients remained
      unchanged. The hemodynamic effects of leg elevation were similar at the different
      concentrations. Changes in parameters of contraction and relaxation during leg
      elevation were coupled and were not altered by desflurane or sevoflurane.
      CONCLUSIONS: Despite their negative inotropic and lusitropic effects, neither
      desflurane nor sevoflurane adversely affect length-dependent regulation of left
      ventricular function. In the conditions of our study, the ability of the left
      ventricular to respond to increased cardiac load is not altered by the use of
      desflurane or sevoflurane.

PMID- 11506107
TI  - Auditory evoked potential index predicts the depth of sedation and movement in
      response to skin incision during sevoflurane anesthesia.
AB  - BACKGROUND: The auditory evoked potential (AEP) index, which is a single
      numerical parameter derived from the AEP in real time and which describes the
      underlying morphology of the AEP, has been studied as a monitor of anesthetic
      depth. The current study was designed to evaluate the accuracy of AEPindex for
      predicting depth of sedation and anesthesia during sevoflurane anesthesia.
      METHODS: In the first phase of the study, a single end-tidal sevoflurane
      concentration ranging from 0.5 to 0.9% was assigned randomly and administered to
      each of 50 patients. The AEPindex and the Bispectral Index (BIS) were obtained
      simultaneously. Sedation was assessed using the responsiveness portion of the
      observer's assessment of alertness-sedation scale. In the second phase of the
      study, 10 additional patients were included, and the 60 patients who were
      scheduled to have skin incisions were observed for movement in response to skin
      incision at the end-tidal sevoflurane concentrations between 1.6 and 2.6%. The
      relation among AEPindex, BIS, sevoflurane concentration, sedation score, and
      movement or absence of movement after skin incision was determined. Prediction
      probability values for AEPindex, BIS, and sevoflurane concentration to predict
      depth of sedation and anesthesia were also calculated. RESULTS: The AEPindex,
      BIS, and sevoflurane concentration correlated closely with the sedation score.
      The prediction probability values for AEPindex, BIS, and sevoflurane
      concentration for sedation score were 0.820, 0.805, and 0.870, respectively,
      indicating a high predictive performance for depth of sedation. AEPindex and
      sevoflurane concentration successfully predicted movement after skin (prediction
      probability = 0.910 and 0.857, respectively), whereas BIS could not (prediction
      probability = 0.537). CONCLUSIONS: Auditory evoked potential index can be a guide
      to the depth of sedation and movement in response to skin incision during
      sevoflurane anesthesia.

PMID- 11506108
TI  - Role of the atrial natriuretic factor in obstetric spinal hypotension.
AB  - BACKGROUND: In recent years, the concept of prophylactic volume expansion to
      prevent hypotension caused by spinal anesthesia has been challenged.
      Investigators have reevaluated the concept of prehydration in the obstetric
      patient and the physiologic mechanisms involved. This article addresses whether
      the hypotensive effects attributed to the atrial natriuretic factor are the
      reason for the apparent failure of prehydration. METHODS: Atrial natriuretic
      factor was measured before (baseline) and 10 min after spinal anesthetic drug
      injection (control) in 48 healthy pregnant patients scheduled for elective
      cesarean section. Sixteen patients received hydration with 15 ml/kg crystalloid
      immediately before spinal anesthesia, 16 patients received the same volume
      starting with the spinal anesthetic injection, and the remaining 16 patients
      received no prehydration (control). Blood pressure, heart rate, ephedrine
      requirements, infused fluids, and urine output were measured. RESULTS: Atrial
      natriuretic factor concentrations increased significantly in prehydrated patients
      but not in the control group. There was a significant correlation in the change
      in atrial natriuretic factor concentrations and urine output but no correlation
      in the control atrial natriuretic factor concentrations and blood pressure or
      ephedrine requirements. Ephedrine requirements and blood pressure did not differ
      significantly among study groups. CONCLUSIONS: Atrial natriuretic factor is a
      potent endogenous diuretic in the pregnant patient but does not appear to be
      involved in short-term cardiovascular homeostasis after spinal anesthesia.
      Prehydration appears to be an ineffective measure to prevent post spinal
      hypotension in the obstetric patient [corrected].

PMID- 11506109
TI  - Gel lubrication of the tracheal tube cuff reduces pulmonary aspiration.
AB  - BACKGROUND: Leakage of fluid occurs along the longitudinal folds within the wall
      of an inflated high-volume, low-pressure cuff. Theoretically, lubrication of the
      cuff with a water-soluble gel might prevent aspiration by plugging the channels
      in the cuff wall. Pulmonary aspiration during anesthesia has been linked with
      postoperative pneumonia and during critical illness causes ventilator-associated
      pneumonia. METHODS: Lubricated cuffs were compared with nonlubricated cuffs for
      leakage of dye placed in the subglottic space to the tracheobronchial tree in a
      benchtop model (n = 5) and in a prospective double-blinded randomized controlled
      trial of anesthetized patients (n = 36). The duration of the efficacy of the
      lubricant was determined in a prospective open observational study of critically
      ill patients with tracheostomies (n = 9). Dye was detected clinically by dye
      coloration of secretions during tracheal suctioning. RESULTS: In the benchtop
      model the incidence of leakage was 0% in the lubrication group and 100% in the
      nonlubrication group (P < 0.01). Dye leakage in anesthetized patients was 11% in
      the lubrication group and 83% in the nonlubrication group (P < 0.0001). In the
      critically ill patients with lubricated cuffed tracheostomy tubes, leakage first
      occurred after a median period of 48 h (range, 24-120 h). CONCLUSIONS: Cuff
      lubrication with a water-soluble gel reduces pulmonary aspiration in anesthetized
      patients. In the critically ill patient with a tracheostomy the protective effect
      is lost after 24-120 h.

PMID- 11506110
TI  - Cardiorespiratory effects of automatic tube compensation during airway pressure
      release ventilation in patients with acute lung injury.
AB  - BACKGROUND: Spontaneous breaths during airway pressure release ventilation (APRV)
      have to overcome the resistance of the artificial airway. Automatic tube
      compensation provides ventilatory assistance by increasing airway pressure during
      inspiration and lowering airway pressure during expiration, thereby compensating
      for resistance of the artificial airway. The authors studied if APRV with
      automatic tube compensation reduces the inspiratory effort without compromising
      cardiovascular function, end-expiratory lung volume, and gas exchange in patients
      with acute lung injury. METHODS: Fourteen patients with acute lung injury were
      breathing spontaneously during APRV with or without automatic tube compensation
      in random order. Airway pressure, esophageal and abdominal pressure, and gas flow
      were continuously measured, and tracheal pressure was estimated.
      Transdiaphragmatic pressure time product was calculated. End-expiratory lung
      volume was determined by nitrogen washout. The validity of the tracheal pressure
      calculation was investigated in seven healthy ventilated pigs. RESULTS: Automatic
      tube compensation during APRV increased airway pressure amplitude from 7.7+/-1.9
      to 11.3+/-3.1 cm H2O (mean +/- SD; P < 0.05) while decreasing trans-diaphragmatic
      pressure time product from 45+/-27 to 27+/-15 cm H2O x s(-1) x min(-1) (P <
      0.05), whereas tracheal pressure amplitude remained essentially unchanged (10.3+/
      3.5 vs. 10.1+/-3.5 cm H2O). Minute ventilation increased from 10.4+/-1.6 to
      11.4+/-1.5 l/min (P < 0.001), decreasing arterial carbon dioxide tension from
      52+/-9 to 47+/-6 mmHg (P < 0.05) without affecting arterial blood oxygenation or
      cardiovascular function. End-expiratory lung volume increased from 2,806+/-991 to
      3,009+/-994 ml (P < 0.05). Analysis of tracheal pressure-time curves indicated
      nonideal regulation of the dynamic pressure support during automatic tube
      compensation as provided by a standard ventilator. CONCLUSION: In the studied
      patients with acute lung injury, automatic tube compensation markedly unloaded
      the inspiratory muscles and increased alveolar ventilation without compromising
      cardiorespiratory function and end-expiratory lung volume.

PMID- 11506111
TI  - Local administration of morphine for analgesia after iliac bone graft harvest.
AB  - BACKGROUND: Harvesting autogenous bone grafts from the ilium may cause
      considerable pain and may represent a significant source of postoperative
      morbidity. The local application of morphine can reduce pain in a rat model of
      bone damage. We evaluated the analgesic efficacy of administering morphine to the
      donor bone graft site for spinal fusionsurgery. METHODS: Sixty patients
      undergoing cervical spinal fusion surgery using autogenous bone harvested from
      the ilium were randomly assigned to one of three groups: Group 1 was given saline
      infiltrated into the harvest site, group 2 was given 5 mg intramuscular morphine;
      group 3 was given 5 mg morphine infiltrated into the harvest site. After surgery,
      all patients were given morphine through a patient-controlled analgesia pump.
      Pain scores both from the harvest and the incision sites, as well as morphine
      use, were recorded at 2, 4, 6, 8, 12, and 24 h after surgery. At 1 yr after
      surgery the presence and subjective characteristics of donor site pain were
      recorded. RESULTS: Total 24-h morphine use (milligrams) was significantly lower
      (P < 0.0001) in group 3 (33.7+/-8.3 mg, mean +/- SD), compared with either group
      1 (64.3+/-6.6 mg) or group 2 (59.6+/-9.3 mg). Pain from the graft site was scored
      the same at 2 h but remained significantly lower (P < 0.0001) for group 3 at all
      later time intervals. Pain scores from the incision site were similar among the
      three study groups. One year after surgery, 25% of patients reported having
      chronic donor site pain. The association of chronic donor site pain was
      significantly higher (P < 0.05) in groups 1 (33%) and 2 (37%) compared with group
      3 (5%). CONCLUSION: Low-dose morphine applied to the harvest graft site can
      reduce local pain, morphine use, and chronic donor site pain after cervical spine
      fusion surgery.

PMID- 11506112
TI  - A new model of electrically evoked pain and hyperalgesia in human skin: the
      effects of intravenous alfentanil, S(+)-ketamine, and lidocaine.
AB  - BACKGROUND: The authors used the analgesics alfentanil, S(+)-ketamine, and
      systemic lidocaine to examine a new human model of experimental pain and
      hyperalgesia. METHODS: Transcutaneous electrical stimulation at a high current
      density (5 Hz, 67.5+/-6.6 mA) was used to provoke acute pain (numeric rating
      scale, 5 of 10), stable areas of secondary mechanical hyperalgesia to pin prick
      (43.6+/-32.1 cm2), and light touch (27.5+/-16.2 cm2) for 2 h. Alfentanil, S(+)
      ketamine, and lidocaine were applied for 20 min in a double-blind, placebo
      controlled, crossover design in 12 subjects using target controlled infusions.
      RESULTS: In the placebo session, pain ratings and areas of hyperalgesia were
      stable during the stimulation period, which facilitated the assessment of
      analgesic effects. Alfentanil effectively inhibited electrically evoked pain and
      reduced pin prick hyperalgesia and allodynia during its infusion. S(+)-ketamine
      induced inhibition of secondary hyperalgesia was more pronounced and lasted for
      the whole experimental protocol. Therapeutic levels of systemic lidocaine showed
      only marginal analgesic effects, but lasting antihyperalgesic effects.
      CONCLUSIONS: A new model of electrically induced pain and hyperalgesia was
      established, which enabled assessment of the time course of analgesic and
      antihyperalgesic effects with high temporal resolution and minimum tissue damage
      and which was further validated by use of common intravenous anesthetics.

PMID- 11506113
TI  - The staircase phenomenon: implications for monitoring of neuromuscular
      transmission.
AB  - BACKGROUND: Repeated indirect stimulation enhances the evoked mechanical response
      of muscle (the staircase phenomenon). There are few data that document the
      magnitude of this effect in man. Inexpensive acceleromyographic monitors of
      neuromuscular function are now available. If these units are to be used as
      scientific tools or clinical monitors, additional information regarding how to
      achieve proper baseline stabilization and calibration is needed. METHODS:
      Anesthesia was induced and maintained with nitrous oxide, propofol, and an
      opioid. Tracheal intubation or laryngeal mask insertion was accomplished without
      muscle relaxants. Thirty adult patients classified as American Society of
      Anesthesiologists physical status I or II were divided into groups of 10. The
      mechanical response of the thumb to supramaximal ulnar nerve stimulation was
      recorded continuously with an acceleromyograph. Group 1 had train-of-four stimuli
      at 15-s intervals for 25 min. Group 2 had single stimuli at 1.0 Hz for 10 min.
      Group 3 had the same stimuli as group 1 except that a 50-Hz tetanus of 5 seconds'
      duration immediately preceded instrument calibration. RESULTS: In group 1,
      average twitch height (T1) increased rapidly to 148+/-19% (mean +/- SD) of
      control at 15 min and then more slowly to reach 158+/-26% of control at 25 min.
      The train-of-four fade ratio did not vary with the duration of stimulation. In
      group 2, T1 increased to 172+/-19% of control after 400 stimuli (6.7 min) and
      180+/-22% of control at 10 min In group 3, average T1 did not decrease below 97+/
      5% or increase above 105+/-15% of control at any time. CONCLUSIONS: A 5-s, 50-Hz
      tetanus administered before initial twitch calibration considerably shortens the
      time required to achieve baseline stability.

PMID- 11506114
TI  - Lack of hypercapnic increase in cerebral blood flow at high blood viscosity in
      conscious blood-exchanged rats.
AB  - BACKGROUND: The hypothesis of a compensatory dilation of cerebral vessels to
      maintain cerebral blood flow at a high blood viscosity was tested during
      hypercapnia in the study after replacement of blood by hemoglobin solutions of
      defined viscosities. If compensatory vasodilation exists at normocapnia at a high
      blood viscosity, vasodilatory mechanisms may be exhausted when hypercapnia is
      added, resulting in a lack of increase in cerebral blood flow at hypercapnia.
      METHODS: In conscious rats, blood was replaced by ultrapurified cross-linked
      hemoglobin solutions that had defined and shear rate-independent low or high
      viscosities (low- and high-viscosity groups). Blood viscosity differed threefold
      between both groups (1.2 vs. 3.6 mP x s). Thereafter, rats inhaled either a
      normal or an increased concentration of carbon dioxide in air. Cerebral blood
      flow was determined by the iodo[14C]antipyrine method. RESULTS: During
      normocapnia, global and local cerebral blood flows did not differ between both
      groups. With increasing degrees of hypercapnia, global and local cerebral blood
      flows were gradually elevated in the low-viscosity group (2.8 ml x mmHg(-1) CO2 x
      100 g(-1) x min(-1)), whereas they remained unchanged in the high-viscosity
      group. CONCLUSIONS: Changes in blood viscosity do not result in changes of
      cerebral blood flow as long as cerebral vessels can compensate for these changes
      by vasodilation or vasoconstriction. However, such vascular compensatory
      adjustments may be exhausted in their response to further pathophysiologic
      conditions in blood vessels that have already been dilated or constricted as a
      result of changes in blood viscosity.

PMID- 11506115
TI  - Allosteric adenosine modulation to reduce allodynia.
AB  - BACKGROUND: Adenosine and adenosine agonists reduce hypersensitivity following
      inflammation and peripheral nerve injury models of chronic pain. Because
      inhibitors of adenosine reuptake or metabolism are also effective at reducing
      hypersensitivity, it is likely that there is a tonic release of spinal adenosine
      in these models. One approach to avoid adverse effects from direct agonists is to
      enhance the effect of the endogenous ligand by administering a positive
      allosteric modulator of its receptor. METHODS: Rats with mechanical
      hypersensitivity after spinal nerve ligation received intrathecal injections of
      adenosine, the allosteric adenosine receptor modulator T62, or their combination,
      or received systemic T62 alone or with intrathecal injection of a specific A1
      adenosine antagonist. RESULTS: Both adenosine and T62 reduced hypersensitivity
      alone, with 50% maximal doses (ED50) of 14+/-5.9 and 3.7+/-0.8 microg,
      respectively. They interacted in an additive manner as determined by
      isobolography. T62 also reduced mechanical hypersensitivity after systemic
      administration (15 mg/kg), and this effect was blocked by intrathecal injection
      of 9 microg of the A1-specific adenosine receptor antagonist 8-cyclopentyl-1,3
      dipropylxanthine. CONCLUSIONS: These results add to previous studies that suggest
      ongoing spinal release of adenosine, which is antiallodynic, in this animal model
      of neuropathic pain. Positive allosteric modulation of the adenosine receptor
      reduces hypersensitivity by a spinal mechanism involving A1 adenosine receptor
      stimulation. Although obvious adverse effects were not observed in this
      investigation, further study is required to determine the feasibility of the use
      of such modulators in the treatment of chronic pain associated with hyperalgesia
      and allodynia.

PMID- 11506116
TI  - Inflammatory pain and hypersensitivity are selectively reversed by epidural
      bupivacaine and are developmentally regulated.
AB  - BACKGROUND: Low doses of local anesthetics applied to the young rat spinal cord
      in vitro have been shown to inhibit C-fiber-evoked responses. The aim of this
      work was to investigate whether such low doses applied epidurally selectively
      reduce nociceptive responses in vivo and to investigate the influence of
      postnatal development on such local anesthetic actions. METHODS: Three groups of
      rat pups aged 3, 10, and 21 days were studied. The threshold of the flexion
      withdrawal reflex to mechanical stimulation was determined in the hind limb at
      each age. Inflammatory pain was induced in the right hind limb with 2%
      carrageenan, causing a reduction in the sensory threshold on that side. The
      difference in threshold between the two sides represents inflammatory
      hypersensitivity. The effect of low-dose epidural bupivacaine on sensory
      thresholds and thus the induced hypersensitivity was also determined for each age
      group. RESULTS: Inflammatory hypersensitivity was selectively attenuated by very
      low doses of bupivacaine (concentration range. 0.004-0.0625%), which did not
      affect the sensory threshold in the contralateral uninflamed limb. This effect
      was also age-related, with younger rats being more sensitive than older rats.
      CONCLUSIONS: The effects of epidural bupivacaine in the infant rat are
      developmentally regulated. Lower doses have a selective analgesic effect that
      decreases with increasing postnatal age.

PMID- 11506117
TI  - Continuous venovenous hemofiltration improves arterial oxygenation in endotoxin
      induced lung injury in pigs.
AB  - BACKGROUND: Hypoxemia is common in septic acute lung failure. Therapy is mainly
      supportive, and most trials using specific inhibitors of key inflammatory
      mediators (ie., tumor necrosis factor alpha, interleukin 1) have failed to prove
      beneficial. The authors investigated if a nonspecific blood purification
      technique, using zero-balanced high-volume continuous venovenous hemofiltration
      (CWH), might improve arterial oxygenation in a fluid-resuscitated porcine model
      of endotoxin-induced acute lung injury. METHODS: Piglets of both sexes weighing
      25-30 kg were anesthetized and mechanically ventilated. After baseline
      measurements, animals received an intravenous infusion of 0.5 mg/kg endotoxin
      (Escherichia coli lipopolysaccharide). One hour after endotoxin, animals were
      randomly assigned to either treatment with CWH (endotoxin + hemofiltration, n =
      6) or spontaneous course (endotoxin, n = 6). At 4 h after randomization, animals
      were killed. Hemofiltration was performed from femoral vein to femoral vein using
      a standard circuit with an EF60 polysulphone hemofilter. RESULTS: Endotoxin
      challenge induced arterial hypoxemia, an increase in peak inspiratory pressure,
      pulmonary hypertension, and systemic hypotension. Treatment with CWH did not
      improve systemic or pulmonary hemodynamics. However, arterial oxygenation was
      increased in endotoxin-challenged animals at 5 h after completion of endotoxin
      infusion, as compared with animals not receiving CVVH (arterialoxygen tension,
      268+/-33 vs. 176+/-67 mm/Hg, respectively, P < 0.01). In addition, treatment with
      CWH attenuated the endotoxin-induced increase in peak inspiratory pressure and
      increased lung compliance. CONCLUSION: These results suggest that nonspecific
      blood purification with high-volume CWH improves arterial oxygenation and lung
      function in endotoxin-induced acute lung injury in pigs, independent of improved
      hemodynamics, fluid removal, or body temperature.

PMID- 11506118
TI  - Possible involvement of cyclic adenosine monophosphate-independent mechanism in
      the positive chronotropic effect of norepinephrine in the isolated guinea pig
      right atrium.
AB  - BACKGROUND: Although both positive chronotropic and inotropic effects of beta
      adrenergic stimulation are thought to be mediated by cyclic adenosine 3'5'
      monophosphate, phosphodiesterase III inhibitors such as amrinone and milrinone
      potentiate the positive inotropic effect of catecholamines with minimum influence
      on the heart rate in clinical setting. The aim of the current study was to
      compare the positive chronotropic effect of norepinephrine with that of forskolin
      to elucidate whether cyclic adenosine monophosphate is relevant to the
      chronotropic effect of norepinephrine. METHODS: Concentration-response curves for
      the positive chronotropic effects of norepinephrine and forskolin on the
      spontaneously beating right atria of guinea pigs were determined in the absence
      and presence of phosphodiesterase inhibitors or ion channel inhibitors. In some
      experiments, the left atria driven electrically were used to determine the
      positive inotropic effect of norepinephrine. RESULTS: Norepinephrine and
      forskolin increased the beating rate in a concentration-dependent manner. The
      positive chronotropic effect of forskolin was potentiated by amrinone and 3
      isobutyl-1-methylxanthine, whereas the positive chronotropic effect of
      norepinephrine was not potentiated by the phosphodiesterase inhibitors. In
      contrast, the positive inotropic effect of norepinephrine was potentiated by
      amrinone. The hyperpolarization-activated inward current inhibitor cesium
      chloride and L-type voltage-dependent Ca2+ current inhibitor verapamil suppressed
      the chronotropic effect of norepinephrine, whereas these inhibitors did not
      affect the chronotropic effect of forskolin. CONCLUSION: Norepinephrine increases
      the spontaneously beating rate by a different mechanism from that of forskolin,
      suggesting that cyclic adenosine monophosphate is causally unrelated to the
      positive chronotropic effect of norepinephrine in the guinea pig heart.

PMID- 11506119
TI  - Neuroprotective effect of low-dose lidocaine in a rat model of transient focal
      cerebral ischemia.
AB  - BACKGROUND: A low concentration of lidocaine (10 microM) has been shown to reduce
      anoxic damage in vitro. The current study examined the effect of low-dose
      lidocaine on infarct size in rats when administered before transient focal
      cerebral isehemia. METHODS: Male Wistar rats (weight, 280-340 g) were
      anesthetized with isoflurane, intubated, and mechanically ventilated. After
      surgical preparation, animals were assigned to lidocaine 2-day (n = 10), vehicle
      2-day (n 12), lidocaine 7-day (n = 13), and vehicle 7-day (n = 14) groups. A 1.5
      mg/kg bolus dose of ildocaine was injected intravenously 30 mm before isehemia in
      the lidocaine 2-day and 7-day groups. Thereafter, an infusion was initiated at a
      rate of 2 mg x kg(-1) x h(-1) until 60 min of reperfusion after isehemia. Rats
      were subjected to 90 min of focal cerebral isehemia using the intraluminal suture
      method. Infarct size was determined by image analysis of 2,3,5
      triphenyltetrazolium chloride-stained sections at 48 h or hematoxylin and eosin
      stained sections 7 days after reperfusion. Neurologic outcome and body weight
      loss were also evaluated. RESULTS: The infarct size was significantly smaller in
      the lidocaine 2-day group (185.0+/-43.7 mm3) than in the vehicle 2-day group
      (261.3+/-45.8 mm3, P < 0.01). The reduction in the size of the infarct in the
      lidocaine 7-day group (130.4+/-62.9 mm3) was also significant compared with the
      vehicle 7-day group (216.6+/-73.6 mm3, P < 0.01). After 7 days of reperfusion,
      the rats in the lidocaine group demonstrated better neurologic outcomes and less
      weight loss. CONCLUSIONS: The current study demonstrated that a clinical
      anriarrhythmic dose of lidocaine, when given before and during transient focal
      cerebral isehemia, significantly reduced infaret size, improved neurologic
      outcome, and inhibited postisehemic weight loss.

PMID- 11506120
TI  - Mechanisms of direct inhibitory action of ketamine on vascular smooth muscle in
      mesenteric resistance arteries.
AB  - BACKGROUND: Ketamine was previously suggested to relax vascular smooth muscle by
      reducing the intracellular Ca2+ concentration ([Ca2+]i). However, no direct
      evidence is available to indicate that ketamine reduces the [Ca2+]i in vascular
      smooth muscle of systemic resistance arteries. METHODS: Endothelium-intact or 
      denuded smooth muscle strips were prepared from rat small mesenteric arteries.
      Isometric force and [Ca2+]i were measured simultaneously in the fura-2-loaded,
      endothelium-denuded strips. In some experiments, only isometric force was
      measured in either the endothelium-intact or beta-escin-treated, endothelium
      denuded strips. RESULTS: In the endothelium-intact strips, lower concentrations
      (< or = 30 microm) of ketamine slightly enhanced norepinephrine-induced
      contraction, whereas higher concentrations (> or = 100 microM) of ketamine
      inhibited both norepinephrine- and KCl-induced contractions. In the fura-2-loaded
      strips, ketamine (> or = 100 microM) inhibited the increases in both [Ca2+]i and
      force induced by either norepinephrine or KCl. Ketamine also inhibited the
      norepinephrine-induced increase in [Ca2+]i after treatment with ryanodine. In the
      absence of extracellular Ca2+, ketamine notably inhibited the norepinephrine
      induced increase in [Ca2+]i, whereas it only minimally inhibited caffeine-induced
      increase in [Ca2+]i. Ketamine had little influence on the [Ca2+]i-force relation
      during force development to stepwise increment of extracellular Ca2+
      concentration during either KCl depolarization or norepinephrine stimulation.
      Ketamine did not affect Ca2+-activated contractions in the beta-escin membrane
      permeabilized strips. CONCLUSIONS: The action of ketamine on contractile response
      to norepinephrine consists of endothelium-dependent vasoconstricting and
      endothelium-independent vasodilating components. The direct vasorelaxation is
      largely a result of reduction of[Ca2+]i in vascular smooth muscle cells. The
      [Ca2+]i-reducing effects are caused by inhibitions of both voltage-gated Ca2+
      influx and norepinephrine-induced Ca2+ release from the intracellular stores.

PMID- 11506121
TI  - Nitrous oxide activates GABAergic neurons in the spinal cord in Fischer rats.
AB  - BACKGROUND: Findings to date indicate that nitrous oxide exerts its
      antinociceptive effect by activating descending noradrenergic neurons. The
      mechanism whereby descending inhibitory neurons, including noradrenergic neurons,
      produce antinociceptive effect remains unclear. Using c-Fos protein as a marker
      for neuronal activation, we examined whether spinal cord neurons activated by
      nitrous oxide are y-aminobutyric acid-mediated (GABAergic) neurons. METHODS:
      Adult male Fischer (a strain in which nitrous oxide shows strong antinociceptive
      properties) and Lewis (a strain in which nitrous oxide lacks antinociceptive
      properties) rats were exposed to either air (control) or nitrous oxide. Frozen
      sections of the spinal cord were either stained for c-Fos or double-stained for c
      Fos and glutamic acid decarboxylase (a rate-limiting enzyme for GABA synthesis)
      and analyzed by standard or confocal microscopy. RESULTS: In Fischer rats, 90 min
      of 75% N2O administration increased the number of c-Fos-positive cells in the
      spinal cord approximately threefold as compared with the control group. The c-Fos
      positive cells induced by nitrous oxide were almost entirely colocalized with
      glutamic acid decarboxylase-positive cells. In contrast, exposure did not change
      the number of c-Fos-positive cells in the spinal cord in Lewis rats. CONCLUSIONS:
      Exposure to nitrous oxide activates GABAergic neurons in the spinal cord. The
      dose-dependence of GABAergic neuronal activation in the Fischer rats and its
      absence in the Lewis rat correlate with antinociceptive responses previously
      reported in these same circumstances. Together, we interpret these data to
      indicate that activation of GABAergic neurons in the spinal cord are involved in
      the antinociceptive action of nitrous oxide.

PMID- 11506122
TI  - Nonhalogenated alkane anesthetics fail to potentiate agonist actions on two
      ligand-gated ion channels.
AB  - BACKGROUND: Although ether, alcohol, and halogenated alkane anesthetics
      potentiate agonist actions or increase the apparent agonist affinity of ligand
      gated ion channels at clinically relevant concentrations, the effects of
      nonhalogenated alkane anesthetics on ligand-gated ion channels have not been
      studied. The current study assessed the abilities of two representative
      nonhalogenated alkane anesthetics (cyclopropane and butane) to potentiate agonist
      actions or increase the apparent agonist affinity of two representative ligand
      gated ion channels: the nicotinic acetylcholine receptor and y-aminobutyric acid
      type A (GABA(A)) receptor. METHODS: Nicotinic acetylcholine receptors were
      obtained from the electroplax organ of Torpedo nobiliana, and human GABA(A)
      receptors (alpha1beta2gamma2L) were expressed in human embryonic kidney 293
      cells. The Torpedo nicotinic acetylcholine receptors apparent agonist affinity in
      the presence and absence of anesthetic was assessed by measuring the apparent
      rates of desensitization induced by a range of acetylcholine concentrations. The
      GABA(A) receptor's apparent agonist affinity in the presence and absence of
      anesthetic was assessed by measuring the peak currents induced by a range of GABA
      concentrations. RESULTS: Neither cyclopropane nor butane potentiated agonist
      actions or increased the apparent agonist affinity (reduced the apparent agonist
      dissociation constant) of the Torpedo nicotinic acetylcholine receptor or GABA(A)
      receptor. At clinically relevant concentrations, cyclopropane and butane reduced
      the apparent rate of Torpedo nicotinic acetylcholine receptor desensitization
      induced by low concentrations of agonist. CONCLUSIONS: Our results suggest that
      the in vivo central nervous system depressant effects of nonhalogenated alkane
      anesthetics do not result from their abilities to potentiate agonist actions on
      ligand-gated ion channels. Other targets or mechanisms more likely account for
      the anesthetic activities of nonhalogenated alkane anesthetics.

PMID- 11506123
TI  - Increased sensitivity to depolarization and nondepolarizing neuromuscular
      blocking agents in young rat hemidiaphragms.
AB  - BACKGROUND: Newborn neuromuscular junctions are more sensitive to d-tubocurarine
      than more mature preparations. It is unclear whether the same modifications occur
      with newer nondepolarizing agents and depolarizing agent succinylcholine. The
      purpose of this study was to determine the relative sensitivity of newborn
      neuromuscular junctions to succinylcholine and five nondepolarizing agents.
      METHODS: The phrenic nerve-hemidiaphragm preparation from 60 rats was used, 30
      aged 9-12 days (newborn) and 30 aged 27-33 days (adult). Five rats from each
      group were exposed to one of six neuromuscular blocking agents (d-tubocurarine,
      cisatracurium, atracurium, vecuronium, rocuronium, and succinylcholine).
      Indirectly elicited twitch tension was measured during control conditions in the
      absence of blocking agent, followed by four concentrations of one of the six
      agents. Concentration-response curves were constructed and the EC50
      (concentration required to produce 50% depression of twitch tension) was
      obtained. Potency ratios (EC50adult/EC50newborn) were derived for each agent.
      RESULTS: Newborn preparations were significantly (P < 0.001) more sensitive than
      their adult counterparts for all six agents tested. For nondepolarizing agents,
      the potency ratio was in the 6-12 range. The EC50adult/EC50newborn were as
      follows, in decreasing potency order: d-tubocurarine, 1.68/0.23 microM;
      cisatracurium, 2.73/0.47 microM; vecuronium, 5.47/0.59 microM; rocuronium,
      9.7/0.78 microM; and atracurium, 12.3/1.9 microM. Succinylcholine was three times
      as potent in newborn rats, with an EC50adult/EC50newborn of 21.3/7.3 microM. The
      ratio for succinylcholine was significantly less than for all nondepolarizing
      drugs (P < 0.02). CONCLUSION: The newborn neuromuscular junction of the rat shows
      an increased sensitivity to all neuromuscular blocking agents tested, including
      succinylcholine. However, the potency ratio was greater for nondepolarizing than
      depolarizing drugs. The optimal dose of these agents for certain situations such
      as cesarean section and anesthesia in neonates should be reassessed.

PMID- 11506124
TI  - Effects of sevoflurane on excitatory neurotransmission to medullary expiratory
      neurons and on phrenic nerve activity in a decerebrate dog model.
AB  - BACKGROUND: Sevoflurane is a new volatile anesthetic with a pronounced
      respiratory depressant effect. Synaptic neurotransmission in canine expiratory
      bulbospinal neurons is mainly mediated by excitatory N-methyl-D-aspartatic acid
      (NMDA) receptor input and modulated by inhibitory gamma-aminobutyric acid type A
      (GABA(A)) receptors. The authors investigated the effect of sevoflurane on these
      mechanisms in decerebrate dogs. METHODS: Studies were performed in decerebrate,
      vagotomized, paralyzed and mechanically ventilated dogs during hypercapnic
      hyperoxia. The effect of 1 minimum alveolar concentration (MAC; 2.4%) sevoflurane
      on extracellularly recorded neuronal activity was measured during localized
      picoejection of the glutamate agonist NMDA and the GABA(A) receptor blocker
      bicuculline in a two-part protocol. First, complete blockade of the GABA(A)ergic
      mechanism by bicuculline allowed differentiation between the effects of
      sevoflurane on overall GABA(A)ergic inhibition and on overall glutamatergic
      excitation. In a second step, the neuronal response to exogenous NMDA was used to
      estimate sevoflurane's effect on postsynaptic glutamatergic neurotransmission.
      RESULTS: One minimum alveolar concentration sevoflurane depressed the spontaneous
      activity of 16 expiratory neurons by 36.7+/-22.4% (mean +/- SD). Overall
      glutamatergic excitation was depressed 19.5+/-16.2%, and GABA(A)ergic inhibition
      was enhanced 18.7+/-20.6%. However, the postsynaptic response to exogenous NMDA
      was not significantly altered. In addition, 1 MAC sevoflurane depressed peak
      phrenic nerve activity by 61.8+/-17.7%. CONCLUSIONS: In the authors' in vivo
      expiratory neuronal model, the depressive effect of sevoflurane on synaptic
      neurotransmission was caused by a reduction of presynaptic glutamatergic
      excitation and an enhancement of GABA(A)ergic inhibition. The effects on
      expiratory neuronal activity were similar to halothane, but sevoflurane caused a
      stronger depression of phrenic nerve activity than halothane.

PMID- 11506125
TI  - Halothane but not isoflurane attenuates interleukin 1beta-induced nitric oxide
      synthase in vascular smooth muscle.
AB  - BACKGROUND: Inducible nitric oxide synthase (iNOS) is induced by endotoxin or
      cytokines, such as interleukin (IL)-1, through a protein synthesis pathway.
      Halothane reportedly inhibits protein synthesis in various tissues. The aim of
      the current study was to examine the effect of halothane on the IL-1beta-evoked
      induction of NOS in vascular smooth muscle. METHODS: After removal of the
      endothelium, arterial rings of rat aorta were mounted in an isometric force
      recording system. The effects of halothane (1.0-3.0%) or isoflurane (3.0%) on IL
      1beta (20 ng/ml)-induced inhibition of the contractile responses to KCl (30 mM)
      and phenylephrine (10(-9)-10(-5) M) were studied. The cyclic guanosine
      monophosphate and cyclic adenosine monophosphate contents were determined by
      radioimmunoassay. Expression of iNOS and iNOS mRNA were measured by Western or
      Northern blot analysis, respectively. RESULTS: Halothane (1.0-3.0%) but not
      isoflurane (3%) significantly reduced the ML-1beta-induced inhibition of
      contraction in a concentration-dependent manner. The cyclic guanosine
      monophosphate content of the vascular smooth muscle increased significantly after
      a 5-h exposure to IL-1beta. Halothane at 3.0% significantly inhibited the
      increase in cyclic guanosine monophosphate content induced by IL-1beta. Halothane
      had no effect on cyclic adenosine monophosphate content. IL-1beta-induced
      expression of iNOS and iNOS mRNA in the rat aorta were inhibited significantly by
      halothane. CONCLUSION: The current study demonstrated that halothane but not
      isoflurane inhibits IL-1beta-stimulated hyporesponsiveness to vasoconstrictive
      agents in vascular smooth muscle and that this inhibitory effect of halothane
      involves the inhibition of iNOS mRNA expression. Thus, these findings suggest
      that halothane may have some sites to affect nitric oxide-signaling pathway.

PMID- 11506126
TI  - Opioid peptide-expressing leukocytes: identification, recruitment, and
      simultaneously increasing inhibition of inflammatory pain.
AB  - BACKGROUND: Inflammatory pain can be effectively controlled by an interaction of
      opioid receptors on peripheral sensory nerve terminals with opioid peptides
      released from immune cells upon stressful stimulation. To define the source of
      opioid peptide production, we sought to identify and quantify populations of
      opioid-containing cells during the course of Freund's complete adjuvant-induced
      hind paw inflammation in the rat. In parallel, we examined the development of
      stress-induced local analgesia in the paw. METHODS: At 2, 6, and 96 h after
      Freund's complete adjuvant inoculation, cells were characterized by flow
      cytometry using a monoclonal pan-opioid antibody (3E7) and antibodies against
      cell surface antigens and by immunohistochemistry using a polyclonal antibody to
      beta-endorphin. After magnetic cell sorting, the beta-endorphin content was
      quantified by radioimmunoassay. Pain responses before and after cold water swim
      stress were evaluated by paw pressure thresholds. RESULTS: In early inflammation,
      66% of opioid peptide-producing (3E7+) leukocytes were HIS48+ granulocytes. In
      contrast, at later stages (96 h), the majority of 3E7+ immune cells were ED1+
      monocytes or macrophages (73%). During the 4 days after Freund's complete
      adjuvant inoculation, the number of 3E7+ cells increased 5.6-fold (P < 0.001,
      Kruskal-Wallis test) and the beta-endorphin content in the paw multiplied 3.9
      fold (P < 0.05, Kruskal-Wallis test). In parallel, cold water swim stress-induced
      analgesia increased by 160% (P < 0.01, analysis of variance). CONCLUSIONS: The
      degree of endogenous pain inhibition is proportional to the number of opioid
      peptide-producing cells, and distinct leukocyte lineages contribute to this
      function at different stages of inflammation. These mechanisms may be important
      for understanding pain in immunosuppressed states such as cancer, diabetes, or
      AIDS and for the design of novel therapeutic strategies in inflammatory diseases.

PMID- 11506127
TI  - Halothane-dependent lipid peroxidation in human liver microsomes is catalyzed by
      cytochrome P4502A6 (CYP2A6).
AB  - BACKGROUND: Halothane is extensively (approximately 50%) metabolized in humans
      and undergoes both oxidative and reductive cytochrome P450-catalyzed hepatic
      biotransformation. Halothane is reduced under low oxygen tensions by CYP2A6 and
      CYP3A4 in human liver microsome to an unstable free radical, and then to the
      volatile metabolites chlorodifluoroethene (CDE) and chlorotrifluoroethane (CTE).
      The free radical is also thought to initiate lipid peroxidation. Halothane
      dependent lipid peroxidation has been shown in animals in vitro and in vivo but
      has not been evaluated in humans. This investigation tested the hypothesis that
      halothane causes lipid peroxidation in human liver microsomes, identified P450
      isoforms responsible for halothane-dependent lipid peroxidation, and tested the
      hypothesis that lipid peroxidation is prevented by inhibiting halothane
      reduction. METHODS: Halothane metabolism was determined using human liver
      microsomes or cDNA-expressed P450. Lipid peroxidation was quantified by
      malondialdehyde (MDA) formation using high-pressure liquid chromatography
      ultraviolet analysis of the thiobarbituric acid-MDA adduct. CTE and CDE were
      determined by gas chromatography-mass spectrometry. RESULTS: Halothane caused MDA
      formation in human liver microsomes at rates much lower than in rat liver
      microsomes. Human liver microsomal MDA production exhibited biphasic enzyme
      kinetics, similar to CDE and CTE production. MDA production was inhibited by the
      CYP2A6 inhibitor methoxsalen but not by the CYP3A4 inhibitor troleandomycin.
      Halothane-dependent MDA production was catalyzed by cDNA-expressed CYP2A6 but not
      CYP3A4 or P450 reductase alone. CYP2A6-catalyzed MDA production was inhibited by
      methoxsalen or anti-CYP2A6 antibody. CONCLUSIONS: Halothane causes lipid
      peroxidation in human liver microsomes, which is catalyzed by CYP2A6, and
      inhibition of halothane reduction prevents halothane-dependent lipid peroxidation
      in vitro.

PMID- 11506128
TI  - Differential modulation of the cardiac L- and T-type calcium channel currents by
      isoflurane.
AB  - BACKGROUND: Volatile anesthetics exert their negative chronotropic and inotropic
      effects, in part by depressing the L- and T-type calcium channels. This study
      examines and compares the dose-dependent effects of isoflurane on atrial L- and T
      type calcium currents (I(Ca,L) and I(Ca,T)) and ventricular I(Ca,L). METHODS:
      Whole cell I(Ca) was recorded from enzymatically isolated guinea pig
      cardiomyocytes. Current-voltage relations for atrial and ventricular I(Ca,L) was
      obtained from holding potentials of -90 and -50 mV to test a potential of +60 mV
      in 10-mV increments. Atrial I(Ca,T) was determined by subtraction of currents
      obtained from holding potentials of -50 and -90 mV. Steady state inactivation was
      determined using standard two-pulse protocols, and data were fitted with the
      Boltzmann equation. RESULTS: Isoflurane depressed I(Ca) in a dose-dependent
      manner, with Kd values of 0.23+/-0.03, 0.34+/-0.03, and 0.71+/-0.02 mM of
      anesthetic for atrial I(Ca,T) and I(Ca,L) and ventricular (ICa,L), respectively,
      and caused a significant (P < 0.05) hyperpolarizing shift in steady state
      inactivation. At 1.2 and 1.6 mm, isoflurane caused a significant (P < 0.05)
      depolarizing shift in the steady state activation in ventricular I(Ca,L) but not
      in atrial I(Ca,L) or I(Ca,T). In addition to the depression of I(Ca,L),
      isoflurane also induced a hyperpolarizing shift in the reversal potential of
      I(Ca) for both atrial and ventricular L-type calcium channels. CONCLUSION: The
      results show that atrial I(Ca,T) is more sensitive to isoflurane than atrial
      I(Ca,L), and ventricular I(Ca,L) was the least responsive to the anesthetic.
      These differential sensitivities of the calcium channels in the atrial and
      ventricular chambers might reflect phenotypic differences in the calcium channels
      or differences in modulation by the anesthetic.

PMID- 11506129
TI  - Spinal endogenous acetylcholine contributes to the analgesic effect of systemic
      morphine in rats.
AB  - BACKGROUND: Systemic morphine is known to cause increased release of
      acetyicholine in the spinal cord. Intrathecal injection of the cholinergic
      receptor agonists or acetyicholinesterase inhibitors produces antinociception in
      both animals and humans. In the present study, we explored the functional
      importance of spinal endogenous acetylcholine in the analgesic action produced by
      intravenous morphine. METHODS: Rats were implanted with intravenous and
      intrathecal catheters. The antinociceptive effect of morphine was determined by
      the paw-withdrawal latency in response to a radiant heat stimulus after
      intrathecal treatment with atropine (a muscarinic receptor antagonist),
      mecamylamine (a nicotinic receptor antagonist), or cholinergic neurotoxins
      (ethylcholine mustard aziridinium ion [AF64A] and hemicholinium-3). RESULTS:
      Intravenous injection of 2.5 mg/kg morphine increased significantly the paw
      withdrawal latency. Intrathecal pretreatment with 30 microg atropine (n = 7) or
      50 microg mecamylamine (n = 6) both attenuated significantly the antinociceptive
      effect of morphine. The inhibitory effect of atropine on the effect of morphine
      was greater than that of mecamylanilne. Furthermore, the antinociceptive effect
      of morphine was significantly reduced in rats pretreated with intrathecal AF64A
      (n = 7) or hemicholinium-3 (n = 6) to inhibit the high-affinity choline
      transporter and acetylcholine synthesis. We found that intrathecal AF64A reduced
      significantly the [3H]hemicholinium-3 binding sites but did not affect its
      affinity in the dorsal spinal cord. CONCLUSIONS: The data in the current study
      indicate that spinal endogenous acetylcholine plays an important role in
      mediating the analgesic effect of systemic morphine through both muscarinic and
      nicotinic receptors.

PMID- 11506130
TI  - Complications and treatment of mild hypothermia.

PMID- 11506131
TI  - The heart in blunt trauma.

PMID- 11506132
TI  - Intravenous clonidine use in a neonate experiencing opioid-induced myoclonus.

PMID- 11506133
TI  - Fatal hepatitis associated with isoflurane exposure and CYP2A6 autoantibodies.

PMID- 11506134
TI  - Mask induction with sevoflurane in a parturient with severe tracheal stenosis.

PMID- 11506135
TI  - Foreign body aspiration: a presenting sign of juvenile myasthenia gravis.

PMID- 11506136
TI  - Nonanesthetics (nonimmobilizers) and anesthetics display different
      microenvironment preferences.

PMID- 11506137
TI  - Antagonism of the 5-HT(3) receptor does not alter isoflurane MAC in rats.

PMID- 11506138
TI  - When is preemptive analgesia truly preemptive?

PMID- 11506139
TI  - Preemptive analgesia by intravenous low-dose ketamine and epidural morphine.

PMID- 11506140
TI  - Improved, but not preemptive, analgesia.

PMID- 11506141
TI  - Draeger Narkomed 6000 poses patient safety risks.

PMID- 11506142
TI  - Ventilator failure during use of a new anesthesia machine.

PMID- 11506143
TI  - Positioning of infants in the prone position: a useful technique.

PMID- 11506144
TI  - Chlamydia trachomatis infection in women: bad news, good news, and next steps in
      prevention.
AB  - Chlamydia trachomatis causes largely asymptomatic infections that can lead to
      pelvic inflammatory disease, infertility, ectopic pregnancy, and chronic pelvic
      pain. Screening women routinely is critical to controlling the epidemic of this
      disease. Testing innovations now make diagnosis easier, and simple treatment
      regimens may improve compliance with medications and increase cure rates, but
      testing and treatment must be coupled with improved screening efforts and
      effective partner services. Ongoing research may point to other interventions
      that will increase our success in fighting chlamydial infections.

PMID- 11506145
TI  - Infection in pregnancy and cerebral palsy.
AB  - Infections in pregnancy, including the most common congenital infections (TORCH:
      toxoplasmosis, rubella, cytomegalovirus, herpes simplex virus), are known causes
      of long-term neurodevelopmental disabilities, although the proportion of children
      with specific disabilities attributable to TORCH infections appears to be 5% to
      10% or less. Intrauterine infection, especially subclinical infection of the kind
      associated with preterm birth, is under investigation as a cause of
      neurodevelopmental disability. These studies have focused almost exclusively on
      cerebral palsy. Summary estimates from a published meta-analysis suggest that
      chorioamnionitis is associated with a twofold increased risk of cerebral palsy in
      preterm and a fivefold increased risk in term children. In some studies, cytokine
      levels in amniotic fluid or newborn blood have also been found to be
      significantly elevated in preterm and term children with cerebral palsy compared
      to controls. These data suggest that factors related to the fetal inflammatory
      response, including cytokines, may be causal agents in brain damage and
      neurodevelopmental disability associated with intrauterine infection. We need to
      greatly improve both our understanding of and our ability to measure the relevant
      exposures related to infection and inflammation, to further understand
      differences in the association between intrauterine infection and cerebral palsy
      relative to gestational age, and to investigate a broad range of
      neurodevelopmental outcomes as potential adverse effects of intrauterine
      infection.

PMID- 11506146
TI  - The risk of infectious diseases among child care providers.
AB  - More than 1.1 million people were employed in out-of-home child care facilities
      in the United States in 1998, and this number is expected to increase over the
      next 10 years. This group consists primarily of women with a median age of 35.
      This review of the literature provides convincing evidence that these women have
      an excess risk of infection with a number of diseases, including cytomegalovirus,
      parvovirus B19, and, possibly, giardia. These workers also face an epidemic risk
      of such other infections as shigellosis, hepatitis A, and cryptosporidiosis.
      Handwashing, good hygiene, and, where indicated, immunization, remain the
      mainstays of prevention for this group.

PMID- 11506147
TI  - Trends in human immunodeficiency virus among adolescents: implications for the
      clinician.
AB  - Human immunodeficiency virus (HIV) is currently a reportable infection in a
      growing number of states, which makes it possible to track patterns of spread
      according to demographic characteristics, risk behavior, and geographic region.
      Lee and Fleming analyzed HIV surveillance results from 1994 to 1998 among women
      age 15 to 44 from the first 25 states to initiate this program. They found that
      new diagnoses increased each year among women who were 15 to 19 in 1994, largely
      in association with heterosexual activity and, to a lesser but increasing extent,
      with injection drug use. HIV infections in older women declined. HIV increased
      during this period in the South, in contrast to the West, Central states, and
      Northeast. This paper suggests that now, even in areas not previously identified
      as HIV epicenters, discussions about HIV and methods to prevent transmission need
      to find their way into the routine care we provide.

PMID- 11506148
TI  - Women living long, living well: community driven women's health priorities.
AB  - The Office on Women's Health of the Department of Health and Human Services led
      an effort to seek feedback on women's health issues. The response showed that
      women in communities nationwide focused less on individual organ-specific health
      issues than on broader strategies they thought were critical to improving and
      sustaining women's health programs. This article summarizes the result of those
      discussions as expressed in the "Women Living Long, Living Well" framework.

PMID- 11506149
TI  - Factors predicting the use of complementary therapies in a multi-ethnic sample of
      early-stage breast cancer patients.
AB  - OBJECTIVES: to examine predictors of use of complementary therapies reported by
      women who had also received standard medical treatment for early-stage breast
      cancer. METHODS: A volunteer sample of 231 black, Hispanic, and non-Hispanic
      white patients with early-stage breast cancer (diagnosed within the preceding
      year) reported their use of complementary therapies. We examined predictors of
      the use of each therapy from among a set of demographic and quality of life
      measures. RESULTS: Most women reported using 1 complementary therapy or more,
      most commonly psychotherapy, support groups, meditation, and spiritual healing.
      Use of psychotherapy related to age, education, and elevated distress. Use of
      other complementary therapies was not related to distress. More black than
      Hispanic or non-Hispanic white patients used herbal therapies and spiritual
      healing. Use of complementary therapies did not relate to expectation of
      recurrence, dissatisfaction with medical care, or (among relevant patients)
      concerns about the consequences of chemotherapy. CONCLUSIONS: Use of healing
      therapies that do not replace medical treatment should be viewed as attempts to
      increase potential benefit and not as signs of distress or dissatisfaction. Use
      of complementary therapies also varies across racial and ethnic groups.

PMID- 11506150
TI  - Comparing the acceptability of manual vacuum aspiration and electric vacuum
      aspiration as methods of early abortion.
AB  - OBJECTIVE: to compare the acceptability of manual vacuum aspiration (MVA) and
      electric vacuum aspiration (EVA) as methods of early (< or = 77 days' gestation)
      abortion. METHODS: We interviewed 42 women who had been randomly assigned to
      either MVA or EVA and compared their perceptions of the two procedures. RESULTS:
      The experiences and perceptions of women in the two groups were similar in many
      ways. The majority of women in both procedure groups were very satisfied with the
      method used, and most indicated that they would prefer the same method if they
      were to have another abortion. CONCLUSION: This study found no major differences
      in the acceptability of MVA and EVA among women undergoing early abortions.

PMID- 11506151
TI  - A gendered epidemic: women and the risks and burdens of HIV.

PMID- 11506152
TI  - Infectious diseases and women's health: link to social and economic development.

PMID- 11506153
TI  - Trends in human immunodeficiency virus diagnoses among women in the United
      States, 1994-1998.
AB  - OBJECTIVE: Since the introduction of combination antiretroviral therapy in 1996,
      acquired immune deficiency syndrome (AIDS) data no longer provide information
      about trends in human immunodeficiency virus (HIV) incidence; therefore, we used
      HIV surveillance data to describe recent trends in HIV diagnoses among women.
      METHODS: Using HIV cases reported from 25 states with confidential HIV reporting,
      we examined new HIV diagnoses from 1994 to 1998 among women born between 1950 and
      1979 by five-year birth cohorts. We adjusted for reporting delays and anticipated
      reclassification of cases reported without exposure risk. RESULTS: During the
      period, 24 171 cases of HIV infection were diagnosed among women. The annual
      number increased 4% from 1994 to 1995, then declined 12% from 1995 to 1998. The
      annual number of diagnoses attributed to heterosexual contact (HC) among women
      age 15 to 19 in 1994 (born 1975-1979) increased 117% from 1994 to 1998. Among
      older women, HC-related diagnoses remained stable or declined. The annual number
      of diagnoses attributed to injection drug use (IDU) among women age 15 to 19 in
      1994 increased 90% from 1994 to 1998. The number of IDU-related diagnoses among
      older women declined between 31% and 59%. Diagnosis rates were higher among HC
      related cases than among IDU cases. The rate for IDU-related diagnoses declined
      by nearly half over the period, but remained stable for HC-related diagnoses.
      CONCLUSIONS: HIV diagnoses among women decreased slightly between 1994 and 1998.
      As the youngest cohort of women reached the age where risk behaviors are
      initiated, however, the number of diagnoses attributed to IDU increased and the
      number of diagnoses attributed to HC more than doubled. It is in this youngest
      cohort, where risk behaviors have only recently been initiated, that HIV
      diagnoses most closely approximate trends in HIV incidence.

PMID- 11506154
TI  - Radical mediated ring opening of 1,2-cyclopropanated-D-glycal: unusual formation
      of S-methylglycosyl-S-methylthiocarbonate.
AB  - Tri-n-butyltin hydride mediated ring opening of 1,2-cyclo- propanated-D-glycals
      led to the formation of 1-C-methyl 2,3-unsaturated sugars. However, corresponding
      catalytic version provided an unusual S-methylglycosyl-S-methyldithiocarbonate
      derivative whose mechanism of formation has been proposed.

PMID- 11506155
TI  - A new mixed acetal-type substitution pattern for alpha-cyclodextrin. Preparation
      of hexakis (3-O-benzyl)- alpha-cyclodextrin.
AB  - alpha-CD was converted into hexakis[2,6-di-O-(methoxydimethyl)methyl]-alpha-CD by
      a proton-catalyzed reaction with 2-methoxypropene. Subsequent benzylation under
      Brimacombe conditions resulted in the fully protected compound, from which the
      acid-sensitive acetal groups were removed to obtain hexakis(3-O-benzyl)-alpha
      cyclodextrin. The structure of all of the compounds synthesized was confirmed by
      13C J-ECHO, COSY, HETCOR and HMBC NMR measurements.

PMID- 11506156
TI  - Synthesis of disaccharides related to the mycobacterial arabinogalactan.
AB  - Several novel glycofuranoses disaccharides related to mycobacterial cell wall
      polysaccharides were synthesized regio- and stereoselectively using 2,3,5-tri-O
      benzoyl-alpha-D-arabinofuranosyl trichloroacetimidate as a glycosyl donor.

PMID- 11506157
TI  - Synthesis and reactivity of a 5-azido analogue of neuraminic acid.
AB  - A peracetylated phenyl 2-thioglycoside (1) of a 5-azido analogue neuraminic acid
      methyl ester was prepared from a known 5-amino precursor by a diazo transfer
      reaction. Glycosidation of 1 by alcohols proceeded smoothly in CH3CN to give
      alpha-sialylated products in good yield.

PMID- 11506158
TI  - Synthesis of oligosaccharide with controlled sequence.
AB  - A simple method for the synthesis of alternate heteropolysaccharide was
      investigated. Two types of modified glucose were combined into a cellobiose-type
      disaccharide monomer having only acetyl groups except a free hydroxyl group at C
      3'. Polycondensation of this monomer, using stannic tetrachloride as catalyst,
      easily gave a novel copolysaccharide having regularly alternating 1,3-beta and
      1,4-beta linkages.

PMID- 11506159
TI  - Highlights: sugars make the decision. GlcNAcbeta-3Fucalpha-Thr(Ser) : a key motif
      in development.

PMID- 11506160
TI  - Synthesis and enzymatic evaluation of mucin type core 4 O-glycan.
AB  - Lactosylaminylated core-4 tetrasaccharide found in mucin type O-glycans has been
      synthesized . The non-reducing galactose residue of the deblocked tetrasaccharide
      was removed by beta-galactosidase from E. coli to produce the corresponding
      GlcNAc terminated compound. The core-2 and core-4 tetrasaccharides were evaluated
      as acceptors for the beta-1,3-N-acetylglucosaminyltransferase (iGnT), beta-1,4
      Galactosyltransferase IV(beta4GalTIV) and beta-1,4-Galactosyltransferase
      I(beta4GalTI).

PMID- 11506161
TI  - Bi-fluorescence-labeled maltoheptaoside: convenient substrate for continual assay
      of alpha-amylase.
AB  - A new maltoheptaose derivative was prepared as a useful substrate for continual
      assay of alpha-amylase. The maltoheptaoside has thionaphtyl group as a
      fluorescent energy donor at the reducing end and dansyl group as an acceptor
      group at the non-reducing end. Excitation of the thionaphthyl group at 290 nm
      results in emission at 523 nm from the dansyl group, while the emission from the
      thionaphthyl group is quenched by the dansyl group. This fluorescence energy
      transfer is reduced by the hydrolytic action with alpha-amylase and a significant
      decrease in the dansyl emission concomitant with an increase in the thionaphthyl
      emission was observed. Usefulness of this substrate was demonstrated for
      sensitive and continuous assay of alpha-amylase from Aspergillus oryzae.

PMID- 11506162
TI  - Modified blood group A trisaccharide probes: synthesis and interaction with
      antibodies.
AB  - Three derivatives modified at the acetamide fragment of blood group trisaccharide
      A, GalNAcalpha1-3(Fucalpha1-2)Galbeta-O-spacer were synthesised. In the first
      compound the amide oxygen was substituted for the sulfur atom. In the second
      compound the methyl group was replaced with the trifluoromethyl moiety, and in
      the third compound the methyl group was replaced with the hydrogen atom. The
      interaction of these probes with anti-A monoclonal antibodies gives the
      information about significance of trisaccharide methyl and carbonyl groups for
      the formation of protein-carbohydrates complex.

PMID- 11506163
TI  - Heck-reaction on alpha-C-p-bromophenyl delta2-glycopyranodise: an easy access to
      functionalized C-aryl glycoside.
AB  - Palladium-catalyzed Heck condensation of C-p-bromophenyl delta2-glycopyranoside
      with methyl vinyl ketone, methyl acrylate, acrylonitrile, or N
      acetyldehydroalanine methyl ester occurred in quite good yields (60-82%).

PMID- 11506164
TI  - Synthesis of branched polysaccharides by polymerization of 6-O-t
      butyldimethylsilyl-D-glucal through stereoregular haloglycosylation.
AB  - In this letter, we report synthesis of branched polysaccharide 2 by glycosylation
      of glucal-type monomer 1 with two free hydroxy groups at position 3 and 4.
      Monomer 1 polymerized with N-halosuccinimide promoter in acetonitrile solvent at
      room temperature--50 degrees C. The product was isolated as a petroleum ether
      insoluble fraction. The structure was determined by 1H and 13C NMR spectra as
      well as elemental analysis to be a polysaccharide consisting of 2-halo-2-deoxy
      alpha-D-mannoside units, indicating that the polymerization proceeded via
      stereoregular glycosylation manner. The molecular weights determined by GPC with
      DMF were 3,300-4,000. The degree of branching was estimated by the NMR data of
      the product from the reaction of 2 with 3,5-dinitrobenzoyl chloride.

PMID- 11506165
TI  - A new bracket system: Control 21. Part I.
AB  - The Control 21 system is a new low energy orthodontic bracket system that
      provides prescriptive variable torque and angulation together with active,
      dimensionally-changing slot geometry.

PMID- 11506166
TI  - Facial aesthetics in orthodontics.
AB  - Current trends in orthodontic care emphasise alternatives to the extraction of
      premolars, despite a lack of support from the refereed literature for many of the
      non-extraction treatments. Anecdotal reports published in non peer-reviewed
      journals have called into question the aesthetic effects of extraction treatment.
      As calls for evidence-based treatments increase throughout dentistry, reports on
      the effects--both positive and negative--of different orthodontic options have
      appeared in growing numbers. Given the results of a variety of reports in the
      peer-reviewed literature, it may be concluded that orthodontic treatment
      involving extractions can produce improved aesthetics for many patients who have
      some combination of crowding and protrusion. However, careful diagnosis followed
      by evidence-based treatment decisions should be the accepted clinical norm as the
      specialty of Orthodontics embarks on its second century.

PMID- 11506167
TI  - Bonding to previously bleached teeth.
AB  - Some authors have reported a decrease in the bond strength of restorative
      composite resin to previously bleached enamel. Since there has been an increase
      in the number of adult patients seeking orthodontic treatment, this study was
      undertaken to determine whether the act of bleaching would somehow affect the
      bonding of orthodontic brackets to enamel surfaces. Sixty extracted premolar
      teeth were divided into 6 groups of 10, for comparison of the shear/peel bond
      strength of orthodontic brackets to enamel using light-cured composite resin
      cement and a resin-modified glass-ionomer cement. For each material, one group of
      teeth was used for bonding to unbleached enamel, and the other two for bonding to
      enamel at 24 hours and 14 days after bleaching. The experimental method simulated
      clinical procedures as closely as possible. No significant difference in the
      shear/peel bond strength was found between the bleached and the unbleached
      groups. t was concluded, therefore, that at-home bleaching with Nite Lite does
      not affect the shear/peel bond strength of light-cured composite resin and resin
      modified glass-ionomer cements used for bracket bonding.

PMID- 11506168
TI  - The localisation of ED1 antibody in the resorbing hard tissues of the
      periodontium.
AB  - A dental hard tissue resorptive model was used to determine the periodontal
      ligament (PDL) distribution of lysosomal membrane antibody ED1 to cells of the
      macrophage-phagocyte lineage. Immunolabel was identified in mononuclear cells
      around inflammatory sites in the PDL, while multinuclear cells were labelled in
      resorption bays present in both bone and dentine. As repair of the tissues
      occurred, the label became less obvious. The presence of strong ED1 label in
      alveolar bone marrow provided evidence supporting the haemopoietic origin of the
      similarly labelled PDL cells. Also, evidence confirming the current theory that
      multinucleated resorptive cells differentiate along a monocyte-macrophage pathway
      was provided. t was concluded that ED1 is a positive PDL marker for mononuclear
      and multinuclear cells involved in the inflammatory and resorptive processes.

PMID- 11506169
TI  - Orthodontic treatment of a mildly crowded malocclusion using the Invisalign
      System.
AB  - The 35-year-old male patient was treated at the University of the Pacific, San
      Francisco U.S.A., as part of an on-going study investigating the feasibility of
      the Invisalign System of tooth movement. The study called for 40 subjects, 10
      with minor, 15 with moderate and 15 with severe tooth deviation. This patient
      fell into the "moderate" degree-of-difficulty category, due to the position of
      the maxillary incisors. Treatment time with the initial series of aligners was 14
      months. Treatment objectives were met, with the exception of adequate anterior
      overbite.

PMID- 11506170
TI  - Non-extraction Tip-Edge appliance management of a moderate Angle Class II
      division 1 malocclusion commenced in the late mixed dentition.
AB  - This case presentation concerns the correction of a moderate Angle Class II
      division 1 malocclusion of a patient whose treatment began during the late mixed
      dentition. Owing to the need to preserve and improve the existing facial
      aesthetics, treatment was started with a non-extraction approach and, in order to
      exploit favourable dentofacial growth changes and to avoid the possibility of
      extraction of teeth, was timed to coincide with the patient's expected adolescent
      growth spurt. Fixed appliances only were used. Special consideration had to be
      made for the patient's fractured upper central incisor teeth. An aesthetically
      pleasing treatment outcome was achieved within the expected time frame for
      correction. The case shows the successful combination of typical Begg
      mechanotherapy used during the early stages of treatment and Tip-Edge rectangular
      archwire mechanotherapy as used for the later and finishing stages.

PMID- 11506171
TI  - Ultrastructural changes in postcapillary-sized venule morphology in aged mouse
      periodontal ligament.
AB  - The aim of this study was to compare the postcapillary-sized venule (PCV)
      morphology of four young ALCA mice (35 days) and four colony-related aged mice
      (365 days) using the transmission electron microscope (TEM). Right and left
      mandibular first molar mesial roots with associated periodontal ligament (PDL)
      and bony socket, were used for TEM assessment. Five PCV profiles were selected at
      each 160 microm interval, from the alveolar crest to the tooth apex. PCV profile
      dimensions were measured on standardised micrographs magnified x2900. Age affects
      were tested using multiple regression analysis. The number of PCV profiles in the
      tooth third of the PDL was higher in aged mice (p < 0.01) and comprised
      predominantly apericytic vessels (p < 0.001). The number of PCV profiles
      increased significantly (p < 0.001) in aged mice in the PDL middle
      circumferential third halfway down the molar root. Age had no significant affect
      on PCV diameter. Aged PDL permeability studies are needed to investigate whether
      the changes in aged PCV profile number are associated with functional
      modification of the PDL microvasculature.

PMID- 11506172
TI  - Effect of oleoyl-estrone treatment on the expression of beta1- beta2- and beta3
      adrenoreceptors in rat adipose tissues.
AB  - Adult female rats received a constant i.v. infusion of oleoyl-estrone (3.5
      pmol/kg day) in a lipidic suspension for 14 days. On days 0 (no treatment), 3, 6,
      10 and 14, as well as on day 14 for controls (receiving only the lipid); the rats
      were killed and the expression of the beta1-, beta2- and beta3-adrenoceptor
      genes, in brown adipose tissue and in subcutaneous and periovaric white adipose
      tissue, were measured by RNA protection assay, and compared with that of
      cyclophyllin. The beta3-adrenoceptor was the most expressed in all adipose
      tissues, whereas beta2 was the less expressed in brown adipose tissue. Oleoyl
      estrone significantly, but moderately, increased the expression of beta
      adrenoceptors in the three adipose tissues: beta1 increased in subcutaneous,
      beta2 and beta3 in periovaric and beta3 in brown adipose tissue. Oleoyl-estrone
      also decreased beta3 expression in subcutaneous white adipose tissue. On day 10,
      adipocytes isolated from periovaric white adipose tissue of oleoyl-estrone
      treated rats showed higher cAMP response to an isoproterenol challenge than the
      controls. The mechanism by which oleoyl-estrone elicits the wasting of fat
      reserves could be mediated by adrenergic pathways, at least in part.

PMID- 11506173
TI  - Interactions of chlorpromazine with milk proteins.
AB  - The mode and nature of the binding of chlorpromazine (CPZ), a psychotropic drug,
      with milk proteins--alpha-lactalbumin (with substantial amounts of alpha-helix,
      beta-sheet and random coil), alpha-lactoglobulin (a major beta-sheeted protein)
      and alphas-casein (a random coiled protein) have been studied
      spectrofluorometrically and spectropolarimetrically. The binding affinity of CPZ
      for unfolded proteins is comparatively less than that of folded proteins although
      the number of binding sites is smaller in the latter case, due to the greater
      extent of binding of CPZ for folded proteins. Thermodynamic analysis reveals that
      CPZ binds to alpha-lactalbumin and alphas-casein in an endothermic (deltaH
      degrees is positive) and hydrophobic manner but with beta-lactoglobulin in an
      exothermic (deltaH degrees is negative) manner. Far UV Circular dichroic studies
      reveal that CPZ increases the secondary structure of the major beta-sheeted
      protein, beta-lactoglobulin possibly by increasing the relative contact orders
      (non-local contacts) within the residues. On the other hand, for proteins
      possessing random coil, it increases the unfolded state of the protein. CPZ does
      not affect local contacts in alpha-helix when its interaction is compared with a
      major alpha-helical protein, myoglobin.

PMID- 11506174
TI  - Purification and characterization of beta-methylaspartase from Fusobacterium
      varium.
AB  - Beta-methylaspartase (EC 4.3.1.2) was purified 20-fold in 35% yield from
      Fusobacterium varium, an obligate anaerobe. The purification steps included heat
      treatment, fractional precipitation with ammonium sulfate and ethanol, gel
      filtration, and ion exchange chromatography on DEAE-Sepharose. The enzyme is
      dimeric, consisting of two identical 46 kDa subunits, and requires Mg2+ (Km =
      0.27+/-0.01 mM) and K+ (Km = 3.3+/-0.8 mM) for maximum activity. Beta
      methylaspartase-catalyzed addition of ammonia to mesaconate yielded two
      diastereomeric amino acids, identified by HPLC as (2S,3S)-3-methylaspartate
      (major product) and (2S,3R)-3-methylaspartate (minor product). Optimal activity
      for the deamination of (2S,3S)-3-methylaspartate (Km = 0.51+/-0.04 mM) was
      observed at pH 9.7. The N-terminal protein sequence (30 residues) of the F.
      varium enzyme is 83% identical to the corresponding sequence of the clostridial
      enzyme.

PMID- 11506175
TI  - Induction of cardiac FABP gene expression by long chain fatty acids in cultured
      rat muscle cells.
AB  - The induction of cardiac FABP expression by long-chain fatty acids was measured
      in cultured rat myoblasts, myotubes and adult cardiomyocytes. With quantitative
      RT-PCR techniques, the primary transcription product of the FABP gene and the
      mature mRNA were measured. Incubations of 30 min resulted in a larger than 2-fold
      increase of the primary transcript in all cells, and FABP mRNA more than doubled
      in myoblasts and cardiomyocytes after 10 h of fatty acid exposure. The results
      demonstrate that long chain fatty acids induce the expression of the cardiac FABP
      gene in muscle cells and their undifferentiated precursors at the level of
      transcription initiation, suggesting that all factors involved in fatty acid
      dependent gene induction are already present in myoblasts. Thus, myoblast cell
      lines should be useful for the characterization of fatty acid response elements
      that control the expression of the FABP gene.

PMID- 11506176
TI  - Effect of lectin from the ascidian on the growth and the adhesion of HeLa cells.
AB  - Cell adhesion molecules, some of which are lectins, play a key role in the
      control of normal and pathological processes of various living organisms. We
      found herein that N-acetyl-D-glucosamine-specific lectin, isolated from the
      ascidian Didemnum ternatanum (DTL), alters the growth properties of HeLa tumor
      cells depending on the anchorage. DTL was shown to increase the proliferation of
      HeLa cells grown in soft agar greatly (in anchorage-independent fashion). In
      contrast, DTL inhibits the proliferative activity of HeLa cells grown on solid
      substrate and acts as inductor of differentiation, slowing cell growth,
      increasing the cell attachment and spreading. Scanning electron microscopic data
      have demonstrated that DTL treatment resulted in pronounced changes of the shape
      and surface of HeLa cells. Changes of cellular morphology correlated with
      essential redistribution of actin microfilaments.

PMID- 11506177
TI  - Estrogen modulates the expression of L-arginine:glycine amidinotransferase in
      chick liver.
AB  - Identification of estrogen-responsive genes is important to understand the
      molecular mechanisms of estrogen action. Suppression subtractive hybridization
      was employed to screen estrogen-responsive genes in chick liver. A single
      injection of estrogen into 6-week-old chick induced up-regulation of several
      known genes encoded for yolk proteins, such as Vitellogenin I and II and very low
      density lipoprotein II (apo-VLDL II). One novel sequence displayed a dramatic
      change (3-fold increase) in response to estrogen treatment. This cDNA fragment
      was extended and the resultant sequence was analyzed. Translated amino acid
      sequence was 90, 88, 83 and 87% identical to the L-arginine:glycine
      amidinotransferase of pig, rat, frog and human, respectively. The sequence has a
      conservative catalytic site of L-arginine: glycine amidinotransferase. The
      expression pattern of this gene in organs is consistent with previous reports of
      L-arginine:glycine amidinotransferase in chick. Thus, this clone represented the
      chicken L-arginine:glycine amidinotransferase. It appeared that estrogen-induced
      alteration of arginine:glycine amidinotransferase was not dependent on protein
      synthesis, because concurrent administration of cycloheximide did not affect the
      estrogen-mediated expression pattern. This is the first study demonstrating that
      L-arginine:glycine amidinotransferase is a target of the estrogen receptor.

PMID- 11506178
TI  - Phosphorylation and activation of protein tyrosine phosphatase (PTP) 1B by
      insulin receptor.
AB  - We have previously reported a direct in vivo interaction between the activated
      insulin receptor and protein-tyrosine phosphatase-1B (PTP1B), which leads to an
      increase in PTP1B tyrosine phosphorylation. In order to determine if PTP1B is a
      substrate for the insulin receptor tyrosine kinase, the phosphorylation of the
      Cys 215 Ser, catalytically inactive mutant PTP1B (CS-PTP1B) was measured in the
      presence of partially purified and activated insulin receptor. In vitro, the
      insulin receptor tyrosine kinase catalyzed the tyrosine phosphorylation of PTP1B.
      53% of the total cellular PTP1B became tyrosine phosphorylated in response to
      insulin in vivo. Tyrosine phosphorylation of PTP1B by the insulin receptor was
      absolutely dependent upon insulin-stimulated receptor autophosphorylation and
      required an intact kinase domain, containing insulin receptor tyrosines 1146,
      1150 and 1151. Tyrosine phosphorylation of wild type PTP1B by the insulin
      receptor kinase increased phosphatase activity of the protein. Intermolecular
      transdephosphorylation was demonstrated both in vitro and in vivo, by
      dephosphorylation of phosphorylated CS-PTP1B by the active wild type enzyme
      either in a cell-free system or via expression of the wild type PTP1B into Hirc-M
      cell line, which constitutively overexpress the human insulin receptor and CS
      PTP1B. These results suggest that PTP1B is a target protein for the insulin
      receptor tyrosine kinase and PTP1B can regulate its own phosphatase activity by
      maintaining the balance between its phosphorylated (the active form) and
      dephosphorylated (the inactive form) state.

PMID- 11506179
TI  - Effects of chronic quercetin treatment on hepatic oxidative status of
      spontaneously hypertensive rats.
AB  - The effects of chronic administration of an oral daily dose of quercetin (10 mg
      Kg(-1)), the most abundant dietary flavonoid, were investigated on hepatic
      oxidative status in spontaneously hypertensive rats and normotensive Wistar Kyoto
      rats. Decreased liver glutathione peroxidase activity, increased liver total
      glutathione levels and increased both hepatic and plasmatic malondialdehyde
      concentrations were observed in spontaneously hypertensive rats when compared to
      Wistar Kyoto rats. In spontaneously hypertensive rats, treatment with quercetin
      for 5 weeks reduced blood pressure, increased glutathione peroxidase activity and
      reduced both plasma and hepatic malondialdehyde levels. However, none of these
      effects were observed in Wistar Kyoto rats. In conclusion, quercetin shows both
      antihypertensive and antioxidant properties in this model of genetic
      hypertension.

PMID- 11506180
TI  - Effect of p58GTA on beta-1,4-galactosyltransferase 1 activity and cell-cycle in
      human hepatocarcinoma cells.
AB  - Beta-1,4-galactosyltransferase 1 (beta1,4-GT 1) is the key enzyme transferring
      galactose to the terminal N-acetylglucosamine (GlcNAc) forming Galbeta3-->4GlcNAc
      structure in the Golgi apparatus. In addition, it also serves as a cell adhesion
      molecule by recognizing and binding to terminal GlcNAc of glycoconjugates on the
      adjacent cell surface and matrix through a subpopulation of the enzyme
      distributed on the cell surface. Transient expression of the p58GTA protein
      kinase, which belongs to the p34cdc2-related supergene family, could enhance
      beta1,4-GT 1 total activity in COS cells. In this study, the p58GTA interaction
      with beta1,4-GT 1 was confirmed using an in vitro assay with the TNT Coupled
      Reticulocyte Lysate System. An expression vector containing p58GTA was stably
      transfected into 7721 cells, a human hepatocarcinoma cell line, expression was
      confirmed by Northern and Western blot analyses. The cells transfected with
      p58GTA (p58GTA/7721) contained 1.9 times higher total beta1,4-GT 1 activity and
      2.6 times higher cell-surface beta1,4-GT 1 activity than the mock transfected
      cells (pcDNA3/7721). However, Ricinus communis agglutinin-I lectin blot analysis
      revealed that the enhanced beta1,4-GT1 activity did not increase the Galbetal-
      >4GlcNAc groups on most of the membrane proteins in p58GTA/7721 cells. By flow
      cytometry analysis, it was found that the p58GTA/7721 cells were G2/M phase
      arrested, compared with the pcDNA3/7721 cells. These results suggest that the
      p58GTA stable transfection into human hepatocarcinoma cells could enhance the two
      beta1,4-GT1 subcellular pool activities independently and change its cell-cycle
      without modifying the beta-1,4-linked galactose residues on most membrane
      proteins.

PMID- 11506181
TI  - Sialic acid binding protein of human endometrium: its regulation by steroids.
AB  - In the present study, we have observed that sialic acid binding protein (SABP - a
      54 kDa glycoprotein which was isolated from human endometrial scrapings taken at
      various stages of the menstrual cycle from normal cycling females and purified to
      apparent homogeneity and was earlier reported from this laboratory) was found in
      sufficiently detectable amount in the endometrium of normal cycling women whereas
      it was found in lesser amount in tissue from women who have recently entered the
      postmenopause stage. SABP was observed in both follicular and luteal phase of
      menstrual cycle which was found by western blot analysis. In the de-novo
      synthesis experiment, synthesis and secretion of SABP was found to be stimulated
      by estradiol (E2) whereas progesterone (P4) was found to have no significant
      stimulatory effect on it which was also confirmed by HEC cell culture. In the HEC
      cell culture, priming of cells with E2 was found to influence the effect of P4 on
      SABP when it was added 2 h after E2 administration. This was observed by doing
      immunoprecipitation followed by SDS-PAGE and autoradiography. Hence this report
      clearly indicates that E2 regulates the synthesis and secretion of 54 kDa SABP
      from human endometrium. How E2 priming of endometrium influences the effect of P4
      on SABP has been discussed.

PMID- 11506182
TI  - The reversal of the inhibition on lipids synthesis by L-659,699 in arterial
      smooth muscle cells cultures.
AB  - The beta-lactone isolated from Fusarium sp. termed L-659,699 is a potent specific
      inhibitor of the enzyme 3-hydroxi-3-methylglutaril coenzyme A (HMG-CoA) synthase.
      In cultures of smooth muscle cells (SMC) isolated from aortic-arch of control (C
      SMC) and 5% of cholesterol diet (Ch-SMC) treated chicks, the incorporation of
      (14C)-acetate to lipids (cholesterol, triacylglycerides and cholesterol ester)
      were greater in Ch-SMC cultures than in C-SMC and the presence of 0.05 microM L
      659,699 for 2 h in the incubation medium decrease the synthesis of cholesterol
      however the triacylglycerides synthesis increase. The effect of inhibitor is
      stronger in young cultures (3-4 steps) than in the older ones (11-12 steps). In
      young C-SMC and Ch-SMC cultures the inhibition of cholesterol and
      triacylglycerides synthesis by L-659,699 was reversal.

PMID- 11506183
TI  - ATP synthesis is coupled to rat liver mitochondrial RNA synthesis.
AB  - Rat liver mitochondria respond to changes in energy demand by modulating the
      amount of RNA synthesized. Coupled rat liver mitochondria were used to determine
      the relationship between mitochondrial respiration, ATP levels, and mitochondrial
      transcription. This system included oxidizable substrates (malate and glutamate)
      and constituents that could support both mitochondrial respiration and
      transcription. The respiratory inhibitor rotenone, phosphorylation inhibitor
      oligomycin, and the uncoupler of oxidative phosphorylation carbonyl-cyanide p
      triflouromethoxyphehylhydrazone inhibited RNA synthesis. Addition of ADP
      stimulated mitochondrial transcription and peak RNA synthesis was observed at 1-2
      mM ADP. At ADP concentrations above 2 mM, RNA synthesis decreased. These results
      demonstrate that mitochondrial transcription is tightly coupled to ATP levels.

PMID- 11506184
TI  - The uptake and metabolism of fructose-1,6-diphosphate in rat cardiomyocytes.
AB  - Fructose-1,6-diphosphate (FDP) is a glycolytic intermediate which has been
      theorized to increase the metabolic activity of ischemic tissues. Here we examine
      the effects of externally applied FDP on cardiomyocyte uptake and metabolism.
      Adult rat cardiomyocytes were isolated and exposed to varying concentrations (0,
      5, 25 and 50 mM) of FDP for either 1, 16 or 24 h of hypoxia (95% N2/5% CO2), each
      time period followed by a 1 h reoxygenation (95% air/5% CO2). The uptake of FDP
      by rat cardiomyocytes was more concentration-dependent than time-dependent.
      Furthermore, the uptake of FDP by the cardiomyocytes was similar in the hypoxia
      and normoxia treated cells. Alamar Blue, a redox indicator that is sensitive to
      metabolic activity, was used to monitor the effects of the FDP on cardiomyocyte
      metabolism. In the 1 h hypoxia or normoxia group, the 5, 10 and 25 mM FDP showed
      a significant increase in metabolism compared to the control cells. When the
      length of hypoxia was extended to 16 h, all doses of FDP were greater than
      control. And at the 24 h hypoxia or normoxia time period, only the 10, 25 and 50
      mM FDP groups were greater than control. The results indicate a non-linear trend
      between the external concentration of FDP and the changes noted in metabolism.
      The findings from this study indicate that a narrow concentration range between 5
      10 mM augments cardiomyocyte metabolism, but higher or lower doses may have
      little additional affect.

PMID- 11506185
TI  - Influence of hyper- and hypothyroidism on lipid peroxidation, unsaturation of
      phospholipids, glutathione system and oxidative damage to nuclear and
      mitochondrial DNA in mice skeletal muscle.
AB  - While the biochemical literature on free radical metabolism is extensive, there
      is little information on the endocrine control of tissue oxidative stress, and in
      the case of thyroid hormones it is mainly limited to liver tissue and to short
      term effects on a few selected biochemical parameters. In this investigation,
      chronic hypothyroidism and hyperthyroidism were successfully induced in mice, and
      various oxidative-stress-related parameters were studied in skeletal muscle. In
      vivo and in vitro lipid peroxidation significantly increased in hyperthyroidism
      and did not change in the hypothyroid state. The fatty acid composition of the
      major phospholipid classes was affected by thyroid hormones, leading to a
      significant decrease in total fatty acid unsaturation both in hypothyroid and
      hyperthyroid muscle in phosphatidylcholine and phosphatidylethanolamine
      fractions. In cardiolipin, however, the double bond content significantly
      increased as a function of thyroid status, leading to a 2.7 fold increase in the
      peroxidizability index from euthyroid to hyperthyroid muscle. Cardiolipin content
      was also directly and significantly related to thyroid state across the three
      groups. Glutathione system was not modified by thyroid state. The oxidative
      damage marker 8-oxo-7,8-dihydro-2'-deoxyguanosine did not change in mitochondrial
      DNA, and decreased in genomic DNA both in hypothyroid and hyperthyroid muscle.
      The results indicate that chronic alterations in thyroid status specially affect
      oxidative damage to lipids in skeletal muscle, with a probably stronger effect on
      mitochondrial membranes, whereas the cytosolic redox potential and DNA are better
      protected possibly due to homeostatic compensatory reactions on the long-term.

PMID- 11506186
TI  - Protective effect of melatonin on naphthalene-induced oxidative stress and DNA
      damage in cultured macrophage J774A.1 cells.
AB  - Naphthalene is a bicyclic aromatic compound that is widely used in various
      domestic and commercial applications. Previous studies in our laboratory have
      demonstrated enhanced production of reactive oxygen species, lipid peroxidation
      and DNA fragmentation in both in vitro and in vivo models following treatment
      with naphthalene. Melatonin (N-acetyl-5-methoxytryptamine), an indole hormone, is
      the chief secretory product of the pineal gland and is an efficient free radical
      scavenger and antioxidant, both in vitro and in vivo. In this study, we have
      investigated the ability of 1 mM melatonin to protect against naphthalene-induced
      oxidative stress and DNA damage in cultured macrophage J774A.1 cells. No
      significant changes were observed when these macrophage cells were treated with
      100 microM naphthalene. Approximately 2.0-, 4.2- and 4.4-fold increases in
      cytochrome c reduction were observed at 200, 400 and 500 mM concentrations of
      naphthalene, demonstrating the increased production of superoxide anion. At 24 h,
      lipid peroxidation increased by approximately 1.4-, 2.1- and 2.2-fold following
      treatment of these cells with 200, 400 and 500 mM concentrations of naphthalene,
      respectively, while 1.6-, 2.8- and 2.8-fold increases in DNA fragmentation were
      observed at these same concentrations. Two hour pretreatment of these cultured
      cells with 1 mM melatonin provided approximately 26-44% decreases in lipid
      peroxidation, superoxide anion production and DNA fragmentation in cells treated
      with 400 and 500 microM naphthalene. Cellular viability decreased significantly
      when cells were incubated with concentrations of naphthalene greater than 100
      microM, while preincubation with melatonin significantly increased the cellular
      viability. These results demonstrate that naphthalene may induce toxic
      manifestations by enhanced production of reactive oxygen free radicals, resulting
      in lipid peroxidation and DNA damage, while preincubation with melatonin
      significantly suppressed cytoxicity in J774A.1 macrophage cells.

PMID- 11506187
TI  - Melatonin enhances Th2 cell mediated immune responses: lack of sensitivity to
      reversal by naltrexone or benzodiazepine receptor antagonists.
AB  - Chronic administration of melatonin for 5 days to antigen-primed mice increased
      the production of pro-inflammatory cytokine IL-10 but decreased the secretion of
      anti-inflammatory cytokine TNF-alpha. These results further confirm that
      melatonin activates Th2-like immune response. Whether melatonin-mediated Th2
      response is dependent on opioid or central and peripheral benzodiazepine
      receptors was also examined. Hence, melatonin was administered to antigen
      sensitised mice with either naltrexone (a mu opioid receptor antagonist) or
      flumazenil (a central benzodiazepine receptor antagonist) or PK11195 (a
      peripheral benzoidiazepine receptor antagonist). No significant difference in
      melatonin-induced Th2 cell response was observed by naltrexone, flumazenil or
      PK11195 treatment. These findings suggest that the Th2 cell response induced by
      melatonin in antigen sensitised mice neither dependent on endogenous opioid
      system nor is modulated through the central or peripheral benzodiazepine
      receptors.

PMID- 11506188
TI  - Activation of multiple MAPK pathways (ERKs, JNKs, p38-MAPK) by diverse stimuli in
      the amphibian heart.
AB  - We investigated the expression and activation of three MAPK subfamilies in the
      isolated perfused amphibian heart. ERK was detected as a 43 kDa band; p38-MAPK
      was detected as a band corresponding to 38 kDa and JNKs were detected as two
      bands corresponding to 46 and 52 kDa, respectively. PMA induced the activation of
      the ERK pathway as assessed by determining the phosphorylation state of ERK and
      the upstream component MEK1/2. PD98059 abolished this activation. p38-MAPK was
      phosphorylated by sorbitol (almost 12-fold, maximal within 10-15 min) and JNKs
      were phosphorylated and activated by sorbitol or anoxia/reoxygenation
      (approximately 4- and 2.5-fold, respectively). SB203580 completely blocked the
      activation of p38-MAPK by sorbitol. These results indicate that the MAPK pathways
      activated by phorbol esters, hyperosmotic stress or anoxia/ reoxygenation in the
      amphibian heart may have an important role in this experimental system.

PMID- 11506189
TI  - Helicobacter infection and phospholipase A2 enzymes: effect of Helicobacter felis
      infection on the expression and activity of sPLA2 enzymes in mouse stomach.
AB  - The murine gastric mucosa possesses very high secretory type phospholipase A2
      activity. Northern and Western blots indicated that the pancreatic-type, sPLA2-IB
      represents the predominant form of sPLA2 enzymes present in the gastric mucosa.
      Both sPLA2-IB mRNA and protein in the gastric mucosa exceeded levels found in the
      pancreas, and in contrast to the pancreatic enzyme it was present primarily in
      the active state. The sPLA2-IB gene is not expressed in the murine small
      intestine and colon. Infection by the gastritis-inducing bacteria,
      Helicobacterfelis (H. felis) dramatically and time dependently decreased the PLA2
      activity in the glandular stomach of the mouse strain, C57BL/6, sensitive to the
      organism, which appeared to be related to a decrease in the percentage of sPLA2
      IB present in the active form. This bacterial-induced reduction in PLA2 activity
      was not observed in BALB/c mice that fail to develop gastritis in response to H.
      felis infection. C57BL/6 mice do not, while BALB/c mice express, the PLA2-II
      enzyme. The H. felis-induced reduction in sPLA2-IB activity may weaken the
      gastric barrier by reducing the local concentration of arachidonic and linoleic
      acid, liberated from membrane phospholipids, the major precursors of
      'cytoprotective' prostaglandins. Data presented here suggest that both sPLA2-IB
      and sPLA2-II enzymes may contribute to the gastric response to Helicobacter
      infection.

PMID- 11506190
TI  - Flavonoids and urate antioxidant interplay in plasma oxidative stress.
AB  - Flavonoids are naturally occurring plant compounds with antioxidant properties.
      Their consumption has been associated with the protective effects of certain
      diets against some of the complications of atherosclerosis. Low-density
      lipoprotein (LDL) oxidative modification is currently thought to be a significant
      event in the atherogenic process. Most of the experiments concerning the
      inhibition of LDL oxidation used isolated LDL. We used diluted human whole plasma
      to study the influence of flavonoids on lipid peroxidation (LPO) promoted by
      copper, and their interaction with uric acid, one of the most important plasma
      antioxidants. Lipid peroxidation was evaluated by the formation of thiobarbituric
      acid reactive substances (TBARS) and of free malondialdehyde (MDA). The
      comparative capability of the assayed flavonoids on copper (II) reduction was
      tested using the neocuproine colorimetric test. In our assay system, urate
      disappears and free MDA and TBARS formation increase during the incubation of
      plasma with copper. Most of the tested flavonoids inhibited copper-induced LPO.
      The inhibition of LPO by flavonoids correlated positively with their capability
      to reduce copper (II). The urate consumption during the incubation of plasma with
      copper was inhibited by myricetin, quercetin and kaempferol. The inhibition of
      urate degradation by flavonoids correlated positively with the inhibition of LPO.
      Urate inhibited the copper-induced LPO in a concentration-dependent mode.
      Luteolin, rutin, catechin and quercetin had an antioxidant synergy with urate.
      Our results show that some flavonoids could protect endogenous urate from
      oxidative degradation, and demonstrate an antioxidant synergy between urate and
      some of the flavonoids.

PMID- 11506191
TI  - Ca2+-antagonists inhibit the N-methyltransferase-dependent synthesis of
      phosphatidylcholine in the heart.
AB  - Evidence indicates that, in addition to the L-type Ca2+ channel blockade, Ca2+
      antagonists target other functions including the Ca2+-pumps. This study was
      conducted to test the possibility that the reported inhibition of heart
      sarcolemmal (SL) and sarcoplasmic reticular (SR) Ca2+-pumps by verapamil and
      diltiazem could be due to drug-induced depression of phosphatidylethanolamine
      (PE) N-methylation which modulates these Ca2+-transport systems. Three catalytic
      sites individually responsible for the synthesis of PE monomethyl (site I),
      dimethyl (site II) and trimethyl (phosphatidylcholine (PC), site III) derivates
      were examined in SL and SR membranes by employing different concentrations of S
      adenosyl-L-methionine (AdoMet). Total methyl group incorporation into SL PE, in
      vitro, was significantly depressed by 10(-6)-10(-3) M verapamil or diltiazem at
      site III. The catalytic activity of site I was inhibited by 10(-3) M verapamil
      only, whereas the site II activity was not affected by these drugs. The
      inhibition induced by verapamil or diltiazem (10(-5) M) was associated with a
      depression of the Vmax value without any change in the apparent affinity for
      AdoMet. Both drugs decreased the SR as well as mitochondrial PE N-methylation at
      site III. A selective depression of site III activity was also observed in SL
      isolated from hearts of rats treated with verapamil in vivo. Furthermore,
      administration of [3H-methyl]-methionine following the treatment of animals with
      verapamil, reduced the synthesis of PC by N-methyltransferase. Verapamil also
      depressed the N-methylation-dependent positive inotropic effect induced by
      methionine in the isolated Langendorff heart. Both agents depressed the SL Ca2+
      pump and although diltiazem also inhibited the SR Ca2+-pump, verapamil exerted a
      stimulatory effect. In addition, verapamil decreased SR Ca2+-release. These
      results suggest that verapamil and diltiazem alter the cardiac PE N
      methyltransferase system. This action is apparently additional to the drugs'
      effect on L-type Ca2+ channels and may serve as a biochemical mechanism for the
      drugs' inhibition of the cardiac Ca2+-pumps and altered cardiac function.

PMID- 11506192
TI  - L-leucine transport in rat heart under normal conditions and effects of a
      simulated hypoxia.
AB  - L-leucine plays a central role in the regulation of protein metabolism in heart
      and has been implicated in myocardial protection, but little is known about the
      relationship between these phenomena and leucine transport across the cardiac
      sarcolemma. In this study we used sarcolemmal vesicles and ventricular myocytes
      isolated from rat heart to characterise L-leucine transport under normal
      conditions and to investigate the effect of simulated hypoxia or inhibition of
      protein synthesis. The Km and Vmax of leucine uptake were 5.24+/-0.65 mM and
      1.43+/-1.84 nmol min(-1) mg(-1) protein in vesicles compared to 2.17+/-0.13 mM
      and 1.7+/-0.76 nmol min(-1) microl(-1) intracellular space in cells. Transport
      was not dependent on Na+ or H+ gradients. In vesicles L-leucine uptake was
      increased by trans-stimulation, whilst inhibition was observed with classical
      system L substrates including 2-aminobicyclo[2,2,1]-heptane-2-carboxylic acid
      (BCH) suggesting that this system mediated L-leucine transport in heart. L
      Leucine uptake into isolated cardiac myocytes was inhibited after 20, 30 and 60
      min of simulated hypoxia. This was not caused by reduced cell viability, although
      the cells underwent a rigor contracture. Inhibition of protein synthesis did not
      affect L-leucine transport.

PMID- 11506194
TI  - Signaling by the JNK group of MAP kinases. c-jun N-terminal Kinase.
AB  - c-Jun N-terminal kinase (JNK) is one of the several main MAP kinase groups
      identified in mammals. Original studies by use of Jurkat T cells implicated JNK
      in T cell activation and interleukin (IL-2) expression. Recent advances using
      mouse genetic approaches have revealed novel functions of this pathway in primary
      mouse T cells. JNK is not essential for T-cell activation; instead, it is
      required for helper T differentiation into effector cells and their cytokine
      production. In this review, we summarize these advances in understanding the
      expression, function, and regulation of the JNK pathway in T-lymphocyte
      activation and differentiation.

PMID- 11506195
TI  - Role of adhesion molecules in activation signaling in T lymphocytes.
AB  - The T cell and antigen-presenting cell communicate to initiate an immune response
      through formation of an immunological synapse. This specialized cell-cell
      junction is compartmentalized into adhesion molecule and T cell receptor enriched
      regions or SMACs. Distinct signals seem to be generated in the T cell receptor
      and adhesion molecule-dominated regions. This review focuses on how these
      distinct signaling pathways may be integrated within the T cell to set thresholds
      for T cell activation, proliferation, and survival.

PMID- 11506196
TI  - Dietary probiotic supplementation enhances natural killer cell activity in the
      elderly: an investigation of age-related immunological changes.
AB  - Many elderly subjects are at increased risk of infectious and noninfectious
      diseases due to an age-related decline in lymphoid cell activity
      (immunosenescence). Noninvasive means of enhancing cellular immunity are
      therefore desirable in the elderly. Previous reports have suggested that dietary
      supplementation could represent an effective means of enhancing the activity of
      circulating natural killer (NK) cells in the elderly. In the present study, we
      have conducted a pre-post intervention trial to determine the impact of dietary
      supplementation with probiotic lactic acid bacteria (LAB) on peripheral blood NK
      cell activity in healthy elderly subjects. Twenty-seven volunteers consumed low
      fat/low-lactose milk supplemented with known immunostimulatory LAB strains
      (Lactobacillus rhamnosus HN001 or Bifidobacterium lactis HN019) for a period of 3
      weeks. A dietary run-in of milk alone was shown to have no significant effect on
      NK cells. In contrast, the proportion of CD56-positive lymphocytes in peripheral
      circulation was higher following consumption of either LAB strain, and ex vivo
      PBMC tumoricidal activity against K562 cells was also increased. Supplementation
      with HN001 or HN019 increased tumoricidal activity by an average of 101 and 62%,
      respectively; these increases were significantly correlated with age, with
      subjects older than 70 years experiencing significantly greater improvements than
      those under 70 years. These results demonstrate that dietary consumption of
      probiotic LAB in a milk-based diet may offer benefit to elderly consumers to
      combat some of the deleterious effects of immunosenescence on cellular immunity.

PMID- 11506193
TI  - Molecular properties and physiological roles of ion channels in the immune
      system.
AB  - The discovery of a diverse and unique set of ion channels in T lymphocytes has
      led to a rapidly growing body of knowledge about their functional roles in the
      immune system. Here we review the biophysical and molecular characterization of
      K+, Ca2+, and Cl- channels in T lymphocytes. Potent and specific blockers,
      especially of K+ channels, have provided molecular tools to elucidate the
      involvement of voltage- and calcium-activated potassium channels in T-cell
      activation and cell-volume regulation. Their unique and differential expression
      makes lymphocyte K+ channels excellent pharmaceutical targets for modulating
      immune system function. This review surveys recent progress at the biophysical,
      molecular, and functional roles of the ion channels found in T lymphocytes.

PMID- 11506197
TI  - Chemokines and their receptors in whiplash injury: elevated RANTES and CCR-5.
AB  - The human sufferings and socioeconomic burden due to whip-lash-associated
      disorders (WAD) are obvious but the pathogenesis of WAD is obscure. The possible
      involvement of the immune system during the disease process in WAD is not known.
      Effector molecules including chemokines and their receptors could play a role in
      WAD. In a prospective study using flow cytometry, we examined percentages of
      blood mononuclear cells (MNC) expressing the chemokines RANTES, MCP-1, MIP
      1alpha, MIP-1beta, and IL-8, the chemokine receptor CCR-5, the T cell activation
      marker CD25, and the T cell chemoattractant IL-16 in patients with WAD and, for
      reference, in healthy controls. Higher percentages of RANTES-expressing blood MNC
      and T cells were observed in patients with WAD examined within 3 days compared to
      14 days after the whiplash injury and, likewise, compared with healthy controls.
      The patients with WAD examined within 3 days after the accident also had higher
      percentages of CCR-5-expressing blood MNC, T cells, and CD45RO+ T cells compared
      to healthy controls. In contrast, there were no differences for any of these
      variables between patients with WAD examined 14 days after injury and healthy
      controls. In conclusion, WAD is associated with a systemic but transient
      dysregulation in percentages of RANTES and CCR-5 expressing MNC and T cells.

PMID- 11506198
TI  - T cell repertoire in primary biliary cirrhosis: a common T cell clone and
      repertoire change after treatment.
AB  - T cell repertoire was analyzed in three early-stage primary biliary cirrhosis
      (PBC) patients, using reverse transcription-polymerase chain reaction and single
      strand conformation polymorphism. Multiple expanded clones were demonstrated in
      livers and peripheral blood lymphocytes (PBL) of all three patients. Comparison
      of the repertoire of different parts of the liver demonstrated the presence of
      common clones in various Vbeta families. Comparison of the repertoire between the
      liver and PBL demonstrated that both CD4 and CD8 T cell clones were expanded.
      Sequence analysis of complementarity determining region 3 of the expanded clones
      revealed that relatively conserved amino acids were utilized in each patient and
      that an identical CD4 T cell clone having Vbeta16 was present in all three
      patients. The number of expanded T cell clones in PBL decreased markedly after
      the treatment with prednisolone. These results suggest that common T cell clones
      may play a pathogenic role in PBC.

PMID- 11506199
TI  - Altered expression of L-selectin (CD62L) on polymorphonuclear neutrophils of
      children vertically infected with human immunodeficiency virus type 1.
AB  - The expression of the leukocyte adhesion molecule L-selectin (CD62L) on
      polymorphonuclear neutrophils (PMN) and circulating levels of the soluble form of
      the receptor (sCD62L) were determined for a group of HIV-1-infected children,
      categorized as having mild or severe disease, and a group of uninfected control
      children. The fluorescence intensity of CD62L on PMN was significantly reduced in
      the HIV-1-infected children with mild disease compared to the uninfected
      controls. The proportion of lymphocytes expressing CD62L, as well as their
      corresponding fluorescence intensities, was significantly reduced in both the
      mild and the severe disease groups compared to the uninfected children, while
      peripheral levels of sCD62L were significantly elevated in the HIV-1-infected
      children with mild and severe disease compared to the controls. Altered cell
      migration resulting from reduced expression of CD62L may be an important
      contributor to the increased susceptibility to secondary microbial infections
      seen in HIV-1-infected children.

PMID- 11506201
TI  - Transport, fate and speciation of heavy metals (Pb, Zn, Cu, Cd) in mine drainage:
      geochemical modeling and anodic stripping voltammetric analysis.
AB  - The maximum concentrations (ppb) of heavy metals in the mine drainage (pH: down
      to 3.3) of Chonam-ri creek in the abandoned Kwangyang gold-silver mine, South
      Korea, are 22600 Zn, 2810 Cu, 182 Cd, and 109 Pb. A small, limestone-infused
      retention pond, about 440 meters downstream from the waste dump, plays an
      important role in the removal of heavy metals: the factors of reduction for Zn,
      Cu, Cd, and Pb are 12, 24, 14, and 14, respectively. This is due to the pH
      increase (up to >5.4) accompanying adsorption onto and/or coprecipitation with Fe
      and Al-hydroxides (goethite and gibbsite). From the waste dump to the pond,
      heavy metal concentrations also progressively decrease due to pH increase.
      Geochemical modeling (using the computer code WATEQ4F) predicts that free aqueous
      metal ions are dominant (mostly >70% for Cu and Zn, and >60% for Pb and Cd) in
      samples collected upstream from the pond, whereas complexing with sulfate,
      carbonate and hydroxyl ions becomes important in the samples collected
      downstream. The comparison between the concentrations of electrochemically labile
      species (determined by Anodic Stripping Voltammetry) and the result of computer
      modeling shows that Cd and Zn are present predominantly as labile inorganic
      species throughout the whole range of the creek. However, Cu and Pb in the
      samples collected downstream from the pond largely form electrochemically inert
      species (possibly, metal-organic complexes). The above results indicate that the
      retention pond is effective in reducing the toxicity of heavy metals, especially
      Cu and Pb.

PMID- 11506200
TI  - Analysis of the costimulatory requirements for generating human virus-specific in
      vitro T helper and effector responses.
AB  - The present study analyzes the role of CD28-B7-mediated costimulation during in
      vitro human peripheral blood memory T cell activation by influenza A virus.
      Inhibition studies using the B7-binding fusion protein CTLA4Ig and antibodies
      against CD80 and CD86 demonstrate that CTLA4Ig and anti-CD86 inhibited influenza
      specific T cell proliferation, interleukin (IL)-2 and interferon (IFN)-gamma
      production, and generation of influenza-specific CD8+ CTL. The production of IL
      10 and IL-18, which are known to modulate T cell immune responses, were not
      affected by blocking the CD28-B7 costimulatory pathway. Inhibition of diverse
      influenza-specific T cell functions could be reversed by the addition of
      exogenous IL-2 or IL-12 but not by the addition of IFN-gamma or IL-18. Although
      IL-2 is known to overcome CD28-B7 costimulatory requirements, this is the first
      report showing that exogenous IL-12 is able to bypass CD28-B7 costimulatory
      blockade induced by CTLA4Ig in vitro. The induction of IFN-gamma production with
      the recently described IFN-gamma inducing cytokine IL-18 was not detected. In
      conclusion, these results demonstrate that CD86 represents a major costimulatory
      signal for the activation of resting peripheral blood memory T cells with recall
      antigens. These observations may have important implications for the development
      of immunotherapeutic strategies in diverse immunodeficiency diseases as well as
      in tumor immunotherapy.

PMID- 11506202
TI  - Separation and preconcentration of lead from aquatic environment using
      Microcystis--based biosorbent.
AB  - The naturally abundant Microcystis surrounded by a slime layer has been
      immobilized as biofilm on a polymer-modified silica gel to obtain a lead
      selective robust column packing material which is recyclable for 70 times without
      any distinct deterioration. The biosorbent has shown quantitative sorption with a
      preconcentration factor of 83 for trace level lead ion (initial concentration
      0.48 microg ml(-1)) in multielemental/natural water samples at pH 5.0 and flow
      rate 1.0 ml min(-1).

PMID- 11506203
TI  - Comparison of two biocides--carbamate and glutaraldehyde--in the control of
      fouling in pulp and paper industry.
AB  - Formation of fouling deposits is a serious problem facing paper mills. Despite
      the search for alternative methods, chemical biocides still represent the chief
      countermeasure to control microbial growth and general fouling buid-up in pulp
      and paper mills. The purpose of this work was to determine the effect of two
      biocides (carbamate and glutaraldehyde) on both planktonic cells and fouling
      layers of a paper machine system. A flow system was used for the study of fouling
      accumulation in an industrial white water circuit. Both biocides proved to be
      more effective in reducing the microbial loading of the white water circuit than
      the deposit accumulated on the stainless steel surfaces. Carbamate, in contrast
      to glutaraldehyde, had the ability of promoting cell agglomeration since the
      microbial loading decreased much more when the white water, treated with
      carbamate, was filtered through a filter-linen. The retention of suspended cells
      in the cellulose fibres acquires major importance since it is obtained by using
      an already existing physical process (filtration), which strongly enhances the
      overall microbial reduction obtained with the addition of the carbamate, without
      increasing the economic costs. These results also suggest that the use of
      conventional retention agents in pulp and paper processes can be efficient in
      controlling unwanted microbial effects.

PMID- 11506204
TI  - Recent developments in chelate degradation.
AB  - Chelating agents are used in various industrial processes to inactivate
      transition metals by forming cyclic complexes. As nitrogen containing compounds,
      these substances increase the nitrogen load in wastewater. Also, they increase
      the heavy metal concentrations in the wastewater effluent. It has been long
      recognised that EDTA and DTPA are relatively recalcitrant compounds and thus pass
      through wastewater treatment without adequate removal. A number of interesting
      studies on the degradability of EDTA and DTPA--either by advanced oxidation
      processes or biological processes--have been carried out recently. This review
      focuses mainly on these two compounds.

PMID- 11506205
TI  - Homogenous and heterogenous advanced oxidation of two commercial reactive dyes.
AB  - Two commercial reactive dyes, the azo dye Reactive Black 5 and the copper
      phythalocyanine dye Reactive Blue 21, have been treated at a concentration of 75
      mg l(-1) by titanium dioxide mediated photocatalytic (TiO2/UV), dark and UV-light
      assisted Fenton (Fe2+/H2O2) and Fenton-like (Fe3+/H2O2) processes in acidic
      medium. For the treatment of Reactive Black 5, all investigated advanced
      oxidation processes were quite effective in terms of colour, COD as well as TOC
      removal. Moreover, the relative growth inhibition of the azo dye towards the
      marine algae Dunaliella tertiolecta that was initially 70%, did not exhibit an
      increase during the studied advanced oxidation reactions and complete
      detoxification at the end of the treatment period could be achieved for all
      investigated treatment processes. However, for Reactive Blue 21, abatement in COD
      and UV-VIS absorbance values was mainly due to the adsorption of the dye on the
      photocatalyst surface and/or the coagulative effect of Fe3+/Fe2+ ions. Although
      only a limited fraction of the copper phythalocyanine dye underwent oxidative
      degradation, 47% of the total copper in the dye was already released after 1 h
      photocatalytic treatment.

PMID- 11506206
TI  - Ultrasonication as a pre-treatment method for the enhancement of the
      psychrophilic anaerobic digestion of aquaculture effluents.
AB  - The effectiveness of ultrasonication as a pre-treatment method for the
      psychrophilic anaerobic treatment of aquaculture effluents was assessed using a 4
      l solids digester. Ultrasonication of aquaculture wastewater was found to enhance
      the removal of chemical oxygen demand by anaerobic digestion by almost 10%. There
      was also a concurrent increase in total biogas production from 0.29 l day(-1) to
      0.45 l day(-1) with a corresponding 10% increase in methane concentration.
      Furthermore, there was an increase of 60% in effluent total ammonia nitrogen
      concentration as a result of sonication in comparison with a 45% increase for
      untreated digester waste.

PMID- 11506207
TI  - Immobilization of arsenic in tailing by using iron and hydrogen peroxide.
AB  - Under environmental conditions, arsenic (As) reveals anionic behavior and is
      converted into various forms in accordance with the Eh/pH condition. This causes
      the difficulty of treating As with other heavy metals in tailing. This study was
      carried out to develop the immobilization method of arsenic in tailing as ferric
      arsenate (FeAsO4) using hydrogen peroxide. According to experimental results, the
      extracted concentrations of arsenic and iron (Fe) from tailing were reduced up to
      84% and 93%, respectively. In the experiment using pure Pyrite (FeS2) and As
      solution, As concentration decreased with an increase of hydrogen peroxide
      dosage. The experimental results of re-extraction showed that only 10% of As and
      20% of Fe were extracted in the case of using hydrogen peroxide. As a result, the
      long-term stability of this method was clarified.

PMID- 11506208
TI  - Uptake of 15N by macrophytes in subsurface-flow wetlands treating domestic
      wastewater.
AB  - Constructed subsurface-flow wetlands are becoming more common for on-site
      treatment of domestic wastewater to provide secondary quality effluent.
      Macrophytes are generally added to wetlands to increase treatment efficiency but
      their role in reducing N content is controversial. Our investigation utilized two
      subsurface-flow wetlands to determine the efficiency of different macrophytes in
      uptake of 15N labeled ammonium sulfate. Macrophytes in Wetland 1 recovered 35% of
      the added N in their shoots but only 5% of the added N was recovered in the
      shoots and roots in Wetland 2. A major difference for the two wetlands was N and
      hydraulic loadings. Wetland 1 received 7.5 Kg N ha(-1)d(-1) and Wetland 2
      received 16.9 Kg N ha(-1)d(-1). Retention time for Wetland 1 based on pore
      volumes was 2.9 d and for Wetland 2 it was 1.2 d. The retardation factor for NH4+
      was approximately 2.5 for both wetlands and the breakthrough curves indicated
      lack of plug flow. The importance of macrophytes in taking up NH4 appeared to
      dependent on N and hydraulic loadings.

PMID- 11506209
TI  - Oxygen dynamics in crude oil contaminated salt marshes: I. Aerobic respiration
      model.
AB  - A simple model was developed to predict oxygen demand exerted by aerobic
      biodegradation of spilled crude oil and fertilizer added to stimulate
      biodegradation in salt marsh sediment. The role of aerobic respiration (AR) was
      determined using first-order G kinetics. The G kinetic rate constants were
      calculated from laboratory data sets through linear regression. The effect of oil
      and fertilizer on AR was quantified by comparing three treatments: (i) control
      (no oil and fertilizer amended), (ii) fertilized, and (iii) oiled and fertilized
      sediments. The effects of dissolved oxygen concentration in the overlying water
      and surface mass transfer coefficient were investigated. Aerobic respiration was
      strongly dependent on the overlying dissolved oxygen concentration when crude oil
      and fertilizer were added. Oiled/fertilized cores did not show higher SOD and AR
      than control cores when overlying DO concentration dropped below 5 mg l(-1).
      Results indicate that higher aerobic respiration in oiled/fertilized is exerted
      by aerobic biodegradation of crude oil and that major biodegradation of crude oil
      occurs only when DO level is high (> 5 mg l(-1)).

PMID- 11506210
TI  - Oxygen dynamics in crude oil contaminated salt marshes: II. Carbonaceous sediment
      oxygen demand model.
AB  - The role of carbonaceous sediment oxygen demand (CSOD) due to oxidation of
      sulfides reduced in oxygen dynamics in crude oil contaminated salt marshes was
      investigated through a mathematical model. An existing CSOD model was calibrated
      from laboratory data sets through nonlinear regression. The effect of oil and
      fertilizer on CSOD was quantified by comparing three treatments (i) control (no
      oil and fertilizer amended) (ii) fertilized, and (iii) oiled and fertilized
      sediments. CSOD was directly proportional to sulfate reduction. Higher CSODs
      under oiled/fertilized and fertilized conditions were primarily due to increased
      sulfate reduction rates under these conditions. Reaction velocity for oxidation
      of dissolved sulfide in the aerobic layer, kappaH2S,d1, was significantly greater
      than that of particulate sulfide oxidation, kappaH2S,p1. This indicates that
      dissolved sulfides are dominant over particulate sulfides and directly related to
      CSOD in salt marshes. The CSOD was linearly dependent on the overlying dissolved
      oxygen concentration when crude oil and fertilizer were added.

PMID- 11506211
TI  - Disabilities in children with Duchenne muscular dystrophy: a profile.
AB  - Proper assessment of disabilities is essential for rehabilitation of patients
      with Duchenne muscular dystrophy. The aim of this study was to identify and
      quantify the disabilities in children with Duchenne muscular dystrophy and
      correlate them with impairment. Thirty-one patients with Duchenne muscular
      dystrophy of age four years and above were studied. The motor functions were
      evaluated using total motor score, upper and lower extremity function grades and
      timed function tests. Disability was quantified with Barthel index. The mean
      scores of motor scales were: total motor score -52 +/- 7.8, total functional
      grade -4.4 +/- 1.9 and timed function score -12.5 +/- 5.8. Barthel index scores
      ranged from 45-95 with a mean of 70.8 +/- 12.7. Motor scales correlated with each
      other and with Barthel index. Thirty children had disabilities in multiple
      spheres of life, which were significantly influenced by the motor power. Barthel
      index was useful in identifying and quantifying specific areas of disabilities in
      these children. Evaluation of disabilities using specific measures may be crucial
      for planning comprehensive management.

PMID- 11506212
TI  - Fracture risk in patients with muscular dystrophy and spinal muscular atrophy.
AB  - We aimed at studying fracture risk in patients with Duchenne's muscular dystrophy
      (DMD), Becker's muscular dystrophy (BEMD), and spinal muscular atrophy type II
      and III (SMA II and III). A self-administered questionnaire was mailed to 293
      patients with DMD, BEMD, SMA II or SMA III of which 229 returned the
      questionnaire. Each respondent was compared with an age- and gender-matched
      control subject. The mean age was 23.9 +/- 15.9 years for the patients and 23.3
      +/- 16.5 years for the controls. There were significantly more fractures among
      patients than controls after the diagnosis was made (RR = 1.9), but not before.
      The patients had more fractures of the femurs, lower legs, and upper arms than
      the controls. Low energy fractures were more frequent in patients than controls
      (9% vs 0%). Many fractures in the femurs (40%), lower legs (35%), and feet and
      toes (44%) led to a permanent loss of function. Loss of ambulation was the major
      risk factor for fractures. In conclusion, fracture risk is increased in
      neuromuscular disease.

PMID- 11506213
TI  - Comparison of two physical exercise programs for the early intervention of pain
      in the neck, shoulders and lower back in female hospital staff.
AB  - The aim of the present study was to compare the effect of increased aerobic
      capacity versus muscle strength rehabilitation of female hospital staff with long
      lasting musculoskeletal back pain. Seventy-nine women agreed to participate in
      the intervention study. After a medical examination, 65 individuals were assigned
      to one of three balanced groups: Endurance training (aerobic capacity promoting
      training: ET: n = 22), strength promotion exercise (SP: n = 24) or a control
      group (CON: n = 19). The active groups met twice a week for 60 minutes of
      exercise over 15 weeks. Aerobic capacity (VO2max) and musculoskeletal pain were
      measured immediately before (T1) and after the intervention period (T2). Aerobic
      capacity significantly increased in the ET group, whereas no change was observed
      in the SP group, and a significant reduction was found in the CON group from T1
      to T2. Musculoskeletal pain was significantly reduced in both intervention
      groups, whereas minor changes were observed in the control group. Results from a
      7-month follow-up (T3) survey confirmed the beneficial effects of interventions
      on musculoskeletal pain. In conclusion, improved aerobic capacity appeared not to
      be a necessary mechanism in musculoskeletal back pain reduction.

PMID- 11506214
TI  - Effects on physical performance and pain from three dynamic training programs for
      women with work-related trapezius myalgia.
AB  - To compare training programs for women with trapezius myalgia regarding physical
      performance and pain, 102 women were randomized to strength, endurance, co
      ordination and non-training groups. Before and after the intervention, static
      strength and dynamic muscular endurance in shoulder muscles were measured on a
      Cybex II dynamometer. Muscle activity in shoulder muscles was monitored via
      surface EMG. The signal amplitude ratio between the active and passive phase of
      repeated contractions indicated the ability to relax. Pain at present, pain in
      general and pain at worst were measured on visual analogue scales. After
      training, within group comparisons showed that the training groups rated less
      pain, and in the strength training group ratings of pain at worst differed from
      the non-training group. Using the non-training group as a reference, static
      strength increased in the strength and endurance training groups and muscular
      endurance in all training groups. The study indicates that regular exercises with
      strength, endurance or co-ordination training of neck/shoulder muscles might
      alleviate pain for women with work-related trapezius myalgia.

PMID- 11506215
TI  - No significant differences between intervention programmes on neck, shoulder and
      low back pain: a prospective randomized study among home-care personnel.
AB  - The effects of two different prevention programmes on: (1) reported neck,
      shoulder and back pain, (2) perceived physical exertion at work and perceived
      work-related psychosocial factors, were evaluated by questionnaires after 12 and
      18 months. Female nursing aides and assistant nurses (n = 282) working in the
      home-care services, were randomly assigned to one of three groups for: (1)
      individually designed physical training programme, (2) work-place stress
      management, (3) control group. Results revealed no significant differences
      between the three groups. However, improvements in low back pain were registered
      within both intervention groups for up to 18 months. Perceived physical exertion
      at work was reduced in the physical training group. Improvements in neck and
      shoulder pain did not differ within the three groups. Dissatisfaction with work
      related, psychosocial factors was generally increased in all groups. As the
      aetiology of neck, shoulder and back disorders is multifactorial, a combination
      of the two intervention programmes might be preferable and should be further
      studied.

PMID- 11506216
TI  - The Spinal Cord Injury Functional Ambulation Inventory (SCI-FAI).
AB  - The development and testing of an observational gait assessment instrument, the
      Spinal Cord Injury Functional Ambulation Inventory (SCI-FAI) is described. To
      assess validity and reliability, 22 subjects with incomplete spinal cord injury
      were scored by four raters. Raters scored each subject three times, once live
      (LS) and twice from videotaped records (VS1, VS2). A moderate-good negative
      correlation (r = -0.742 and -0.700, for VS1 and VS2, respectively) was found
      between the gait score and time required to walk a demarcated path. Inter-rater
      reliability was moderate-good for the live score and the videotaped records (ICC
      = 0.703, 0.800, and 0.840, respectively). Intra-rater reliability was good (ICC =
      0.903, 0.960, 0.942, and 0.850 for Raters 1-4, respectively). To assess
      sensitivity, another group of 19 subjects with SCI were assessed prior to and
      following participation in an intensive walking program. A moderate correlation
      was found between change in gait score and change in lower extremity strength
      (Pearson r = 0.58). These results indicate that the SCI-FAI is a reliable, valid
      and sensitive measure of walking ability in individuals with spinal cord injury.
      In addition, the results suggest that gait analysis using this instrument is
      equally reliable whether the observation is performed live or from videotaped
      records.

PMID- 11506217
TI  - Cross-cultural adaptation of the Minnesota Living with Heart Failure
      Questionnaire for German-speaking patients.
AB  - We performed a cross-cultural adaptation of the "Minnesota Living with Heart
      Failure Questionnaire" (LHFQ) for use in German-speaking chronic heart failure
      patients. The instrument was translated and back translated, pre-tested and
      reviewed by a committee. The German version was tested in 114 patients with
      chronic heart failure. Reliability was assessed by a test-retest procedure and
      Cronbach's coefficient alpha of internal consistency (0.94). To assess concurrent
      validity, we compared the LHFQ sum scores with the New York Heart Association
      classification rating (r = 0.53; p < 0.0001), the 6-minute walk (r = -0.39; p <
      0.0001), the left ventricular ejection fraction (r = -0.24; p = 0.011) and big
      endothelin (r = 0.27; p = 0.004). Construct validity on the LHFQ scores in
      comparison with the Medical Outcomes Study SF-36 Health Survey (MOS SF-36) was
      significant (-0.41 to -0.74; all p < 0.0001). The reliability and validity of the
      German version of the LHFQ was proved; the questionnaire can be recommended for
      use in future clinical trials.

PMID- 11506218
TI  - Key dimensions of client satisfaction with assistive technology: a cross
      validation of a Canadian measure in The Netherlands.
AB  - The purpose of this study was to conduct a cross-validation of the bidimensional
      structure of a satisfaction measure with assistive technology. Data were drawn
      from a follow-up study of 243 subjects who had been administered the Dutch
      version of the Quebec User Evaluation of Satisfaction with assistive Technology
      (QUEST). Ratings related to 12 satisfaction items were analysed. Factor analysis
      results showed that the underlying structure of satisfaction with assistive
      technology consists of two dimensions related to assistive technology, Device
      (eight items) and Services (four items), accounting for 40% of the common
      variance. This finding was consistent with a previous Canadian study and was
      interpreted as supporting the adequacy and stability of the QUEST measure of
      satisfaction. Although the structure is delineated, further studies are
      recommended to support its use in European countries.

PMID- 11506219
TI  - Targeted use of exoglycosidase digestion for the structural elucidation of
      neutral O-linked oligosaccharides.
AB  - Exoglycosidase digestion in combination with the catalog-library approach (CLA)
      is used with matrix-assisted laser desorption/ionization Fourier transform mass
      spectrometry (MALDI-FTMS) to obtain the complete structure of oligosaccharides.
      The CLA is a collision-induced dissociation (CID)-based method used to determine
      the structure of O-linked neutral oligosaccharides. It provides both linkage and
      stereochemical information. Exoglycosidases are used to confirm independently the
      validity of the CLA. In some cases, the CLA provides structural information on
      all but a single residue. Exoglycosidase is used to refine these structures. In
      this way, exoglycosidase use is targeted employing only a small number of
      enzymes. Exoglycosidase arrays, which have been used with N-linked
      oligosaccharides, is avoided despite the larger variations in structures of O
      linked species.

PMID- 11506220
TI  - Prediction of peptide ion mobilities via a priori calculations from intrinsic
      size parameters of amino acid residues.
AB  - Ion mobility spectrometry (IMS) has recently been established as a powerful tool
      to separate the protease digest mixtures and identify their peptide components.
      As accurate calculation of mobilities is critical for this technique, a new rapid
      method based on intrinsic size parameters (ISPs) of amino acid residues has been
      devised. However, those parameters had to be obtained by tedious statistical
      analysis of a large body of experimental data. Here we demonstrate that they can
      instead be derived a priori, based on the stoichiometry of a residue. Our main
      finding is that the ISP of a residue is essentially determined by its density,
      that is, the average mass/size ratio of its constituent atoms. This is in
      accordance with an interpretation in which peptides assume compact conformations
      in the gas phase dominated by the solvation of ionic charge.

PMID- 11506221
TI  - Electron loss from multiply protonated lysozyme ions in high energy collisions
      with molecular oxygen.
AB  - We report on the electron loss from multiply protonated lysozyme ions Lys-Hn(n)+
      (n = 7 - 17) and the concomitant formation of Lys-Hn(n+1)+. in high-energy
      collisions with molecular oxygen (laboratory kinetic energy = 50 x n keV). The
      cross section for electron loss increases with the charge state of the precursor
      from n = 7 to n = 11 and then remains constant when n increases further. The
      absolute size of the cross section ranges from 100 to 200 A2. The electron loss
      is modeled as an electron transfer process between lysozyme cations and molecular
      oxygen.

PMID- 11506222
TI  - Elongated conformers of charge states +11 to +15 of bovine ubiquitin studied
      using ESI-FAIMS-MS.
AB  - Recent advancements in high-field asymmetric waveform ion mobility spectrometry
      (FAIMS) have led to significant improvements in the application of this
      technology to the study of protein conformers. Compared with previous work, the
      maximum value of the separation voltage (i.e., the dispersion voltage) has
      increased, thereby enabling multiple, elongated conformers of individual charge
      states of bovine ubiquitin to be separated in the gas phase (e.g., four
      conformers of each of the +11 and +12 charge states were separated). The use of a
      carrier gas mixture of 40% nitrogen and 60% helium changed the separation
      selectivity compared with pure nitrogen and enhanced the signal intensity,
      especially for the +14 and +15 charge states (the latter was not detected in a
      nitrogen carrier gas). Conformer cross sections were determined using the
      FAIMS/energy-loss method and found to be similar within a given charge state. The
      cross sections for conformers of charge states +13, + 14, and +15 plateau at
      about 2000 A2 suggesting that the structure of bovine ubiquitin is essentially
      unfolded after the addition of the 13th proton.

PMID- 11506223
TI  - Fragmentation and reactions of two isomeric O-alkyl S-(2-dialkylamino)ethyl
      methylphosphonothiolates studied by electrospray ionization/ion trap mass
      spectrometry.
AB  - An initial investigation into the electrospray ionization ion trap mass
      spectrometry (ESI/ITMS) of simple organophosphorus compounds [1] demonstrated
      that detailed structural information could be obtained by sequential
      fragmentation of the ions using collision induced dissociation (CID). Several
      novel fragmentations/rearrangements were observed and it was apparent that the
      full potential of this approach could not be exploited until a more detailed
      understanding of the ion fragmentations was obtained. Such an understanding will
      only result from a detailed study of a wide range of compounds. The present paper
      describes the investigation of two isomeric organophosphates of particular
      relevance to chemical warfare convention (CWC) considerations.

PMID- 11506224
TI  - Residue mass plot and abundance plot: detection of isobaric interferences in DE
      MALDI-TOF-mass spectra of complex polymer mixtures.
AB  - Mass spectra of complex polymer mixtures often disturbed by overlapping homologue
      peak series have been interpreted by means of the novel techniques of the residue
      mass plot and the abundance plot. The model substance used for the investigations
      is so far poorly characterized non-ionic emulsifier Cremophor EL (polyoxyl 35
      castor oil) (CrEL), a heterogeneous polyethoxylate mixture. Because of its high
      amount of hydrophobic and hydrophilic components, CrEL was separated into two
      fractions, aqueous and methanolic, by cation exchange (CCaEx) chromatography.
      CrEL was then subjected to delayed extraction matrix-assisted laser
      desorption/ionization time of flight mass spectrometry (DE-MALDI-TOF-MS).
      Evaluation of the mass spectra was performed by comparing the residue masses of
      the homologue peak series with the calculated residue masses of potential
      components of the excipient cationized with Na+ and K+. A number of these series
      are overlapping because they differ in their theoretical residue masses by about
      0.05 Da. The detection of these isobaric interferences was the basic requirement
      for our analysis method. This goal was achieved by high mass accuracy of the
      measurements (obtained by internal calibration) in combination with two newly
      developed evaluation methods, the residue mass plot and the abundance plot. Using
      this combined technique, generally applicable for complex polymer mixtures, it
      was shown that the aqueous CCaEx fraction contains hydrophobic components such as
      di- and triesters of ricinoleic acid and polyethylene glycol as well as glycerol
      polyoxyethylene di- and triricinoleates, whereas the methanolic fraction contains
      hydrophilic components, mainly polyethylene glycol (PEG) and glycerol
      polyoxyethylene ether. Moreover, free PEG was shown to consist of PEG 800 in
      contrast to the value of 600 Da described so far in literature.

PMID- 11506226
TI  - Ter-body intermediates in the gas phase: reaction of ionized enols with tert
      butanol.
AB  - In the gas phase, the CH2CHOH.+ enol radical cation 1 as well as its higher
      homologues CH3CHCHOH.+ 2 and (CH3)2CCHOH.+ 3, undergo exactly the same sequence
      of reactions with tert-butanol, leading to the losses of isobutene, water and
      water plus alkene. Fourier transform ion cyclotron resonance (FT-ICR) experiments
      using labeled reactants as well as ab initio calculations show that independent
      pathways can be proposed to explain the observed reactivity. For ion 1, taken as
      the simplest model, the first step of the reaction is formation of a proton bound
      complex which gives, by a simple exothermic proton transfer, the ter-body
      intermediate [CH2CHO., H2O, C(CH3)3+]. This complex, which was shown to possess a
      significant lifetime, is the key intermediate which undergoes three reactions.
      First, it can collapse to yield tert-butylvinyl ether with elimination of water.
      Second, by a regiospecific proton transfer, this complex can isomerize into three
      different ter-body complexes formed of water, isobutene and ionized enol. Within
      one of these complexes, which does not interconvert with the others, elimination
      of isobutene leads to the formation of a solvated enol ion. Within the others, a
      cycloaddition-cycloreversion process can proceed to yield the ionized enol 3
      (loss of water and ethylene channel).

PMID- 11506225
TI  - Ionization and collision-induced fragmentation of N-linked and related
      carbohydrates using divalent cations.
AB  - Maltoheptaose and several N-linked glycans were ionized by electrospray as
      adducts with the divalent cations Mg2+, Ca2+, Mn2+, Co2+ and Cu2+. [M + metal]2+
      ions were the major species in all cases with calcium giving the highest
      sensitivity. In addition, copper gave [M + Cu]+ ions. Other cations gave singly
      charged ions only by elimination of a protonated monosaccharide. Fragmentation of
      the [M + metal]2+ ions produced both singly and doubly charged ions with the
      relative abundance of doubly charged ions decreasing in the order Ca > Mg > Mn >
      Co > Cu. Singly charged ions were formed by elimination of a protonated
      monosaccharide residue followed, either by successive monosaccharide residue
      losses, or by a 2,4A cross-ring cleavage of the reducing-terminal monosaccharide.
      Formation of doubly charged fragments from [M + metal]2+ ions involved successive
      monosaccharide-residue losses either with or without O,2A or 2,4A cross-ring
      cleavages of the reducing-terminal monosaccharide. Abundant diagnostic doubly
      charged ions formed by loss of the 3-antenna from the O,2A cross-ring product
      were specific to [M + Ca]2+ ions. Fragmentation of [M + Cu]+ ions was similar to
      that of the corresponding [M + H]+ ions in that most cross-ring fragments were
      absent.

PMID- 11506227
TI  - Gas-phase SN2 reactivity of dicoordinated borinium cations using pentaquadrupole
      mass spectrometry.
AB  - We report gas phase ion/molecule reactions between dialkoxyborinium cations (RO
      B+-OR) and small organic amides, such as N,N-dimethylformamide and N,N
      diethylpropionamide. Besides direct addition at boron, the results show efficient
      SN2 methyl transfer from the borinium ion to the amide. Isotopic labeling and
      collision-induced dissociation (CID) of the methyl transfer products demonstrate
      O-methylation of the amide. Methyl substitution at the alpha-carbon of the amide
      affects the degree of alkylation and adduct formation. Direct proton abstraction
      via beta-elimination is a major competitive reaction for substituents other than
      methyl. Ab initio calculations at the B3LYP/6-31G(d) level indicate that SN2
      transmethylation is highly exothermic with O-methylation favored over N
      methylation by 14.8 kcal/mol.

PMID- 11506228
TI  - Cyclization of ortho-cyclopropylphenyl benzamides in gas and liquid phases.
AB  - The electron ionization (EI) and collision-induced dissociation (CID) spectra of
      substituted N-(ortho-cyclopropylphenyl)benzamides 1-7 and N-[ortho-(1
      methylcyclopropyl)phenyl]benzamides 8-12 were recorded. In addition to routine
      bond cleavages, the molecular ions (M+) of 1-12 undergo cyclization into the
      corresponding 3-aryl-1-alkyl-1-ethyl-1H-benzoxazines and isomeric 5-ethyl-2
      oxodibenzoazepines. The presence of a methyl group in the cyclopropyl ring
      (compounds 8-12) makes the formation of 5-ethyl-2-oxodibenzoazepine less
      favorable. In accord with mass spectrometric predictions, compound 13 (3-p-tolyl
      1-ethyl-1H-benzoxazine) was obtained as a major product of the reaction of N
      (ortho-cyclopropylphenyl)-4-methylbenzamide 1 with sulfuric acid. Traces of 5
      ethyl-2-oxodibenzoazepine were also detected in gas chromatography-mass
      spectrometry (GC-MS) analysis of the reaction mixture although the yield was too
      low to allow its isolation.

PMID- 11506229
TI  - Gangliosides from human granulocytes: a nano-ESI QTOF mass spectrometry
      fucosylation study of low abundance species in complex mixtures.
AB  - Nano-ESI QTOF MS was used for sensitive mapping and sequencing of single
      molecular species in complex ganglioside mixtures obtained from human
      granulocytes, where the fucosylated carbohydrate chains of granulocyte
      gangliosides carry sLex and VIM-2 epitopes postulated to interact with E-selectin
      of the blood vessel wall in the early phase of the inflammation process.
      Functionally relevant components are expressed only at a low level, but using the
      negative ion detection it is possible to trace and identify such species, which
      were not detectable even by TLC. Advantage of the low-energy CID fragmentation
      for low abundance components of the complex ganglioside mixtures in the negative
      ion mode is to produce clear-cut series of fragment ions for sequencing.
      Fucosylation analysis carried out for each molecular species by MS/MS permits the
      clear distinction between sLex and VIM-2 epitope. VIM-2 epitope was expressed in
      all species with a longer sugar core, while in the short oligosaccharide chain
      with a sLex only, using biological material at a mid-femtomol level detection.

PMID- 11506230
TI  - Human tolerance to Gz acceleration loads generated in high-performance
      helicopters.
AB  - BACKGROUND: As the Gz capabilities of tactical helicopters increase, the risk to
      unprotected helicopter aircrew resulting from the physiologic response to
      transitions from -1 Gz (push) to +4.5 Gz (pull) loads needs to be addressed.
      METHODS: There were 9 volunteers who participated in a study conducted at the
      Veridian Operations Centrifuge Facility in Warminster, PA. A 1-h mission scenario
      consisting of nine helicopter maneuvers, based on inflight G measurements (push
      pull mission, PPM), simulated both current (CM: -0.2 to +3.5 Gz) and projected
      future platform capabilities (FM: -1 Gz to +4.5 Gz). Additional scenarios were
      run in which push transitions were limited to +1 Gz (GM). Measurements included
      blood pressure (BP), heart rate (HR), loss of vision, and subjective fatigue.
      RESULTS: Visual decrements were minimal during CM while muscular tensing was
      required to avoid blackout during FM. Light loss typically occurred during the
      transition from -Gz to +Gz. Within the scope of these tests, subjects tolerated
      the range of Gz stresses associated with current U.S. Navy rotary wing platforms.
      When subjected to FM G-loads (typical of current U.S. Army high-performance
      platforms), cardiovascular stress significantly increased, Gz tolerance dropped
      as much as 1.2 G, and HR increased as much as 67 bpm. Cardiovascular changes were
      significantly greater during FM PPM relative to GM. Four subjects reported Almost
      Loss of Consciousness (A-LOC) symptoms during FM. CONCLUSIONS: While G-stress
      experienced by aircrew generated by current helicopters does not appear to
      present a high risk, G-awareness training is recommended to reduce risks to
      aircrew exposed to G-loads generated by more aggressive helicopters. Future
      studies are required to determine the impact of longer mission times and
      dehydration.

PMID- 11506231
TI  - A mechanical model of cerebral circulation during sustained acceleration.
AB  - BACKGROUND: High positive Gz may result in inadequate blood supply to the brain
      even if the central blood pressures are maintained at normal levels. We use a
      mechanical model to simulate the influence of sustained +Gz on cerebral
      circulation. METHODS: The model consists of ascending and descending tubes
      representing the extracranial arteries and veins, respectively, and a cranium in
      which the tubes are enclosed within water-filled rigid container to account for
      the skull and the cerebrospinal fluid. A thick-walled Tygon tube and a thin
      walled surgical drain tube were used for the arteries and veins, respectively.
      The flow of water was driven by a pressure difference at the model ends, and the
      change in the gravitational vector was accomplished by tilting the model.
      RESULTS: The flow drops with an increasing tilt angle only if the descending arm
      collapses. However, when the pressures at the model ends are sufficiently
      elevated, the flow is restored to normal value. In the cranium model, the
      pressure in the water surrounding the tubes always stays close to the pressure in
      the surgical tubing. Consequently, the tubes in the container do not collapse.
      CONCLUSIONS: The principal effect of Gz on flow through the model occurs via
      changes in the resistance of the collapsed descending arm. As the pressures at
      the model ends are elevated, the descending arm opens and the flow increases. The
      pressure in the cranium model is dictated by the condition that the volume of the
      container has to remain constant.

PMID- 11506232
TI  - Efficacy of wrist/palm warming as an EVA countermeasure to maintain finger
      comfort in cold conditions.
AB  - INTRODUCTION: This study explored the effectiveness of local wrist/palm warming
      as a potential countermeasure for providing finger comfort during extended
      duration EVA. METHODS: There were six subjects (five males and one female) who
      were evaluated in a liquid cooling/warming garment (LCWG) wearing modified liquid
      cooling/warming (LCW) gloves in three different experimental conditions:
      Condition 1: Stage 1--no LCWG, LCW glove inlet water temperature 33 degrees C;
      Stage 2--no LCWG, LCW glove inlet water temperature cooled to 8 degrees C; Stage
      3--no LCWG, LCW glove inlet water temperature warmed to 45 degrees C; Condition
      2: Stage 1--LCWG and LCW glove inlet water temperature 33 degrees C; Stage 2-
      LCWG inlet temperature cooled to 31 degrees C, LCW gloves, 8 degrees C; Stage 3-
      LCWG inlet water temperature remains at 31 degrees C, LCW glove inlet water
      temperature warmed to 45 degrees C; Condition 3: Stage 1--LCWG and LCW gloves 33
      degrees C; Stage 2--LCWG inlet water temperature cooled to 28 degrees C, LCW
      gloves, 8 degrees C; Stage 3--LCWG remains at 28 degrees C, LCW glove water
      temperature warmed to 45 degrees C. RESULTS: Wrist/palm area warming showed a
      statistically significant increase in finger temperature (Tfing) in Stage 3
      compared with Stage 2. Blood perfusion showed a trend toward a significantly
      greater value in Stage 3 compared with Stage 2. The LCW gloves were significantly
      more effective in increasing Stage 3 Tfing in Condition 1 (33 degrees C) compared
      with Condition 3 (28 degrees C). Across conditions, subjective perception of heat
      in the hands was significantly greater at Stage 3 than Stage 2; perception of
      overall body heat showed a trend for higher heat ratings in Stage 3 than Stage 2.
      CONCLUSIONS: Local wrist/palm warming was effective in increasing blood
      circulation to the distal upper extremities, suggesting the potential usefulness
      of this technique for enhancing astronaut comfort during EVA while decreasing
      power requirements.

PMID- 11506233
TI  - Spaceflight alters bone mechanics and modeling drifts in growing rats.
AB  - BACKGROUND: Alterations in bone metabolism may be a particularly serious
      consequence of spaceflight and a major obstacle to long-term space exploration.
      The effects of spaceflight on bone mechanics are unclear. This study examined the
      effects of spaceflight on bone mechanics in a growing rat model during a 17-d
      mission aboard the space shuttle (STS-78). METHODS: There were 18 rats that were
      divided into 3 experimental groups: flight rats (n = 6), ground-based control
      rats housed in an animal enclosure module (AEM, n = 6), and ground-based control
      rats housed in standard vivarium caging (n = 6). At the conclusion of the
      mission, rat femurs were tested in three-point bending followed by static and
      dynamic bone histomorphometry. RESULTS: Maximum stress was unaffected by
      spaceflight, but flexural rigidity was significantly decreased in flight animals.
      Much of the decrease appeared to be the result of decreases in tissue properties
      (elastic modulus) rather than structural changes within the bone. No significant
      differences in cortical bone mass or geometry were observed. In contrast,
      endocortical resorption was significantly decreased in flight rats accompanied by
      a nonsignificant decrease in periosteal bone formation, suggesting alterations in
      bone modeling drifts during spaceflight. For nearly all measured indices, ground
      based AEM rats displayed values intermediate to flight and ground-based vivarium
      rats. CONCLUSIONS: Spaceflight can impair tissue properties in femoral cortical
      bone during growth without significant decreases in bone mass or geometry.

PMID- 11506235
TI  - Oral contraceptives, exercise, and acute mountain sickness in women.
AB  - BACKGROUND: Previous research has found that exercise exacerbated acute mountain
      sickness (AMS) in men. PURPOSE: The current study tested this relationship in
      women taking oral contraceptives. METHODS: We studied seven women at 428 mmHg for
      10 h; once while at rest (R) and once while performing intermittent exercise
      (EX). RESULTS: AMS scores had a slight increase at 9 vs. 0 h at altitude in both
      trials (p < 0.05). Resting measurements of ventilation (VE), arterial oxygen
      saturation (SPO2), end tidal O2 (PETO2), and end tidal CO2 (PETCO2) were not
      different over time or between trials (p > 0.05). While fluid intake did not
      change, urine output increased during the 0-3 h period, regardless of trial, and
      returned to baseline values by the 6-9 h period (218 +/- 37 vs. 121 +/- 22 ml x
      h(-1); p < 0.05). During exercise, SPO2 significantly dropped compared with
      similar time points in R (73.1 +/- 1.1 vs. 85.7 +/- 1.8%; p < 0.05). Despite
      exercise-induced desaturation, the AMS scores were not significantly different
      between R and EX. CONCLUSION: These results suggest that oral contraceptives may
      cause a compensation for the physiological responses to exercise critical for the
      development of AMS.

PMID- 11506234
TI  - Increased and decreased expression of CD69 and CD23, respectively, in gravity
      stressed lymphocytes.
AB  - BACKGROUND: Recent studies have shown that gravity-changing stress modulates
      expression levels of cell surface molecules on human lymphocytes. However,
      previous in vitro microgravity studies have been performed with lymphocytes
      treated with mitogenic agents. HYPOTHESIS: The aim of the study was to test if
      exposure of cells to gravity-changing stress alone alters the expression levels
      of cell surface molecules. Specifically, we examined whether the expression of
      activation markers is altered after exposure of lymphocytes to combinations of
      microgravity and hypergravity. METHODS: We used free-fall in parabolic flight for
      human subjects and a drop-shaft to expose peripheral blood mononuclear cells
      (PBMC) to gravity-changing stress. After such exposure, PBMC were isolated, and
      expression levels of CD69, CD23 and CD38 were estimated using three-color flow
      cytometry. RESULTS: Increased percentages of CD69-positive cells were observed
      with PBMC from 3 of 4 volunteers who undertook 10 parabolic flights. Exposure of
      blood to gravity-changing stress in the drop-shaft increased both ratios of CD69
      positive cells and levels of CD69 expression on T and B cells. In contrast, the
      percentages of CD23-positive B cells was decreased. However, gravity-changing
      stress was not always followed by significant alteration in CD38 expression.
      CONCLUSIONS: Our findings suggest that CD69 and CD23 might be useful markers that
      are up- and down-regulated, respectively, after exposure of lymphocytes to
      gravity-changing stress.

PMID- 11506236
TI  - Accommodation of females in the high-G environment: the USAF Female Acceleration
      Tolerance Enhancement (FATE) Project.
AB  - BACKGROUND: In 1993, the U.S. Secretary of Defense opened combat aircraft
      assignments to women. To verify the adequacy of acceleration (+Gz) protection for
      female high-G aircrew, USAF investigators conducted fit tests of standard and
      developmental G-protective equipment and determined the effectiveness of a unique
      laboratory modification (AL Mod) of the standard (CSU-13B/P) anti-G suit during
      gender-comparative centrifuge evaluations. METHODS: Investigators determined
      relaxed +Gz tolerance and straining endurance to +4.5 to +7 Gz and +5 to +9 Gz
      simulated aerial combat maneuver (SACM) centrifuge profiles (4.5-7 SACM: 8
      females and 10 males; and 5-9 SACM: 6 females and 8 males, respectively).
      Additionally, in the 5-9 SACM study, between and within gender SACM endurance
      differences were assessed before and after female subjects' use of the AL Mod.
      Ten female subjects also were fit tested in extended coverage, developmental G
      protective equipment. RESULTS: There was no gender difference in 4.5-7 SACM
      endurance. Male 5-9 SACM endurance exceeded that of females in the unmodified CSU
      13B/P (p < 0.05), but gender parity was achieved when females wore the AL Mod.
      Fit modifications of developmental G-protective equipment were not required, but
      smaller sizes of the standard CSU-13B/P and a developmental anti-G suit were
      indicated and developed. CONCLUSION: In properly fitted anti-G suits, gender
      parity in SACM endurance is achievable; however, full accommodation of female
      aircrew in the high-G environment will require the AL Mod and/or smaller sized
      anti-G suits.

PMID- 11506237
TI  - Pre-existing pulmonary thromboembolic disease in passengers with the "economy
      class syndrome".
AB  - BACKGROUND: Pulmonary emboli, which have occurred in association with air travel,
      in the past have been thought to have arisen from deep venous thromboses (DVT)
      which formed during the flight. HYPOTHESIS: This study was performed to test the
      idea that not all pulmonary emboli which occur following air travel are the
      result of inflight DVT formation. METHODS: Fourteen cases of fatal "economy class
      syndrome" were examined histologically to determine the age of the fatal
      thromboemboli. RESULTS: In 5 of the cases, evidence of pre-existing pulmonary
      thromboembolic disease was present and in 4 of these cases the fatal
      thromboemboli observed in the lung tissue pre-dated the flight. Fresh perimortem
      thrombus without evidence of organization or hemosiderin deposition was observed
      in 9 cases. CONCLUSIONS: The commonly held pathological mechanism that the
      conditions of the flight lead to DVT formation and subsequent pulmonary embolism
      are not applicable in all cases of "economy class syndrome" and thus other
      pathophysiological mechanisms must be entertained.

PMID- 11506238
TI  - Evaluation of flexible cloth electrodes for electrodermal activity recording.
AB  - BACKGROUND: Instrument selection for recording physiological data in flight
      studies requires careful attention to subject comfort and non-interference with
      aircrew activities. Several electrode types and recording sites may be used to
      examine electrodermal activity (EDA). Placement of electrodes on the foot
      minimizes interference with physical activity and reduces motion artifacts;
      however, use of conventional, hard-plastic-encased metal (PEM) electrodes within
      a flight boot can produce discomfort and pressure-induced artifacts. HYPOTHESIS:
      When applied with proper electrolyte gels, thin, flexible, silver-impregnated
      cloth electrodes should acquire EDA signals qualitatively similar to those
      acquired using conventional, PEM electrodes. METHODS: EDA responses evoked by
      light flashes, auditory stimuli and valsalva maneuvers were recorded with cloth
      and PEM electrodes simultaneously from both feet of 4 male subjects. Performance
      of cloth vs. PEM electrodes and variability of signals recorded with the same
      electrode type were examined by placing pairs of selected electrodes on each foot
      of the subjects. Placements were balanced with respect to age and handedness of
      the subject and the number of trials with each electrode type placed on the left
      or right foot. RESULTS: Qualitatively similar signals were recorded with cloth
      and PEM electrodes. Cloth electrodes showed more variability between electrodes
      of the same type. CONCLUSION: For EDA recording, cloth electrodes can perform at
      least as well as PEM electrodes, making it practical to take advantage of the
      cloth electrodes' flexibility and lower profile.

PMID- 11506239
TI  - G-transition effects and their implications.
AB  - G-transition effects are defined as the spectrum of physiological and
      psychophysical effects induced by rapid changes in gravitoinertial forces,
      alternating between hypogravity (<1 Gz) and hypergravity (>1 Gz) and vice versa.
      They appear to involve the cardiovascular and spatial orientation systems. This
      note attempts to briefly review past and current research efforts on the
      consequences of G-transitions and to examine potential confounding Coriolis
      induced bias in both ground-based and inflight research. A brief review of
      current evidence of vestibular influence on orthostatic compensation and their
      implications for G tolerance is presented. The effects of roll-induced
      hypogravity on subsequent G tolerance and possible misperception of attitude
      during roll rotation are discussed. An integrated approach is recommended for
      future research on acceleration and disorientation.

PMID- 11506240
TI  - Isolated troponin I elevation in acute myocardial infarction: a case report.

PMID- 11506241
TI  - Advanced gestational age and fetal lactate levels in flight.

PMID- 11506242
TI  - Optimal time in the menstrual cycle for spacewalks.

PMID- 11506243
TI  - Relationship of CogScreen-AE to flight simulator performance and pilot age.

PMID- 11506244
TI  - Severe lupus nephritis: importance of re-evaluating the histologic classification
      and the approach to patient care.
AB  - The histopathology of severe lupus glomerulonephritis comprises distinct patterns
      of injury which were initially defined by the World Health Organization
      Classification of 1982 as focal and segmental glomerulonephritis (category III),
      diffuse proliferative glomerulonephritis (category IV) and complex membranous
      glomerulonephritis (categories Vc, Vd). It is assumed that the morphologic
      abnormalities demonstrated in this classification represent distinctive
      differences in the mediation of the immune response which leads to a specific
      type of glomerular inflammation. In 1995 the World Health Organizational
      committee recommended a change in categorization of focal and segmental
      glomerulonephritis (class III) and diffuse proliferative glomerulonephritis
      (class IV), which would overlook the morphological differences between these
      categories and treat them as a continuum, recommending that biopsies classified
      as focal and segmental glomerulonephritis (category III) with involvement of > or
      =50% of glomeruli be included into the diffuse proliferative glomerulonephritis
      category (category IV). Since the classification of severe lupus nephritis has
      significant impact on prognosis and the therapeutic approach to patients with
      this disease, it is the purpose of this review to critically re-examine the
      existing classification based on new insights into differences in morphologic
      features and long-term outcome.

PMID- 11506245
TI  - Silica and renal diseases: no longer a problem in the 21st century?
AB  - Silicosis and other occupational diseases are still important even in the most
      developed countries. In fact, at present, silica exposure may be a risk factor
      for human health not only for workers but also for consumers. Furthermore, this
      exposure is associated with many other different disorders besides pulmonary
      silicosis, such as progressive systemic sclerosis, systemic lupus erythematosus,
      rheumatoid arthritis, dermatomyositis, glomerulonephritis and vasculitis. The
      relationships between these silica-related diseases need to be clarified, but
      pathogenic responses to silica are likely to be mediated by interaction of silica
      particles with the immune system, mainly by activation of macrophages. As regards
      renal pathology, there is no single specific clinical or laboratory finding of
      silica-induced nephropathy: renal involvement may occur as a toxic effect or in a
      context of autoimmune disease, and silica damage may act as an additive factor on
      an existing, well-established renal disease. An occupational history must be
      obtained for all renal patients, checking particularly for exposure to silica,
      heavy metals, and solvents.

PMID- 11506246
TI  - Prospective randomized controlled multicenter trial on steroids plus ramipril in
      proteinuric IgA nephropathy.
AB  - Recent studies have shown that steroids improve renal survival and reduce
      proteinuria in IgA nephropathy (IgAN) patients with moderate urinary protein
      excretion and normal renal function. However, this effect seems to diminish over
      time. Moreover, it has been demonstrated that long-term use of ramipril reduces
      the risk of end-stage renal disease in proteinuric diabetic and non-diabetic
      chronic nephropathies. We have planned a long-term unblinded, prospective,
      centrally randomized, controlled, multicentric trial to assess whether combined
      treatment of steroids and ramipril is superior to ramipril alone in patients with
      progressive IgAN disease. A minimum of 134 patients with biopsy-proven IgAN,
      grade G3 or G4, daily proteinuria > 1.0 g and creatinine clearance > 50 mL/min
      will be enrolled during a 2-year recruitment period. The patients will be
      allocated randomly to receive a six-month course of oral prednisone (1.0
      mg/Kg/day for 2 months, tapered by 0.2 mg/Kg/day every month) plus ramipril (2.5
      mg/day for one month, increased by 1.25 mg/day every month to achieve and
      maintain a blood pressure less than 120-80 mm Hg and/or to reduce daily
      proteinuria to 1.0 g or less or by at least 50%) in the experimental group or
      ramipril alone in the control group. Ramipril will be administered during the
      whole 5-year follow-up period in both groups. The primary endpoint will be renal
      survival estimated by 50% increase in baseline serum creatinine; the secondary
      endpoints will be urinary protein and cytokine excretion and side-effects.
      Analyses will be done by intention to treat. A p <0.05 will be taken as
      significant.

PMID- 11506247
TI  - The role of alpha-smooth muscle actin and platelet-derived growth factor-beta
      receptor in the progression of renal damage in human IgA nephropathy.
AB  - BACKGROUND: The degree of tubulointerstitial damage can be considered a better
      indicator of renal function outcome in IgA nephropathy (N) than the extent of
      glomerular sclerosis. MATERIALS AND METHODS: To investigate the pathogenetic
      mechanisms of interstitial injury in IgAN, we used immunohistochemistry and in
      situ hybridization to evaluate the glomerular and tubolointerstitial expression
      of PDGF-beta receptor (R) and alpha-smooth muscle actin (SMA), two markers of
      mesenchymal cell activation, and correlated these findings with the
      histopathologic and clinical features of the disease. We studied 155 IgAN
      patients, divided into three groups based on the histological findings (mild,
      moderate and severe histological lesions). RESULTS: In normal kidneys and in
      patients with mild histological lesions, the interstitial areas showed scattered
      peritubular cells positive for PDGF-betaR and alpha-SMA, with a distribution
      resembling the capillary network. In the glomeruli several cells (mainly in the
      mesangial area) stained for PDGF-betaR, but only very few cells were positive for
      alpha-SMA. Alpha-SMA and PDGF-betaR staining, as expected, was also observed in
      vascular smooth muscle cells. Compared to patients with mild histological
      lesions, alpha-SMA expression was strikingly increased in patients with moderate
      to severe lesions, particularly in areas of tubulointerstitial fibrosis. In these
      patients, PDGF-betaR gene and protein expression, at the tubulointerstitial
      level, paralleled that in alpha-SMA. Both signals were significantly correlated
      with the interstitial damage (interstitial infiltrate and fibrosis).
      Interestingly, these patients showed a different pattern of distribution of alpha
      SMA and PDGF-betaR in the glomeruli: PDGF-betaR expression was upregulated,
      whereas no changes were seen in alpha-SMA staining. In addition, glomerular PDGF
      betaR staining was significantly correlated with mesangial cell proliferation,
      while alpha-SMA was not. Image analysis showed that 40.2+/-10.3/1,000 microm2 of
      interstitial cells were positive to both PDGF-betaR and alpha-SMA, but only 2.8+/
      1.8/1,000 microm of glomerular cells expressed both signals. CONCLUSIONS: Our
      study supports the hypothesis that interstitial PDGF-betaR and alpha-SMA positive
      cells may play a key role in the pathogenesis of tubulointerstitial damage.

PMID- 11506248
TI  - Circulating VEGF and TGF-beta1 in children with idiopathic nephrotic syndrome.
AB  - RATIONALE: The implications of vascular endothelial growth factor (VEGF) and
      transforming growth factor-beta (TGF-beta) on the development of proteinuria were
      studied by measuring the mRNA and protein levels of VEGF and TGF-beta1 in 43
      children with primary nephrotic syndrome. METHODS: Twenty-seven patients were in
      the active nephrotic phase at the time of sampling (Group 1), and 16 were in
      remission (Group 2). In Group 1, 16 were steroid-responders (Group 1a) and 11
      were nonresponders (Group 1b). Minimal change lesion (MCL) in 11 patients and
      focal segmental glomerulosclerosis (FSGS) in 8 were confirmed by renal biopsy.
      The mRNA expressions of peripheral blood lymphocytes and the plasma levels of
      proteins were measured by semi-quantitative RT-PCR and ELISA, respectively.
      RESULTS: Plasma VEGF concentration was higher in Group 1 (204+/-137 pg/mL) than
      Group 2 (91+/-72 pg/mL) (P=0.002). However, there was no significant difference
      either between Group 1a (184+/-146 pg/mL) and Group 1b (258+/-134 pg/mL) or
      between patients with FSGS (330+/-122 pg/mL) and those with MCL (146+/-112
      pg/mL). The VEGF mRNA expression showed changes similar to VEGF protein
      expression, and there was no statistical significance. Plasma levels and mRNA
      expressions of TGF-beta1 were similar in all groups. CONCLUSIONS: These results
      suggest that circulating VEGF is associated with proteinuria both in steroid
      responsive and steroid-resistant primary nephrotic syndrome in children.

PMID- 11506249
TI  - Vascular endothelial growth factor (VEGF) levels in peritoneal dialysis effluent.
AB  - BACKGROUND: Long-term peritoneal dialysis (PD) patients who develop peritoneal
      ultrafiltration failure have an abnormally large number of capillaries and
      sclerotic changes in peritoneal biopsy. Peritoneal vascular endothelial growth
      factor (VEGF) production has been suggested to explain the higher levels in
      peritoneal effluent than in plasma. The high effluent VEGF levels have been
      related to peritoneal changes consisting of increased permeability to small
      molecules. To further analyze the relationship between peritoneal neoangiogenesis
      induced by VEGF and peritoneal transport, we studied peritoneal effluent VEGF
      levels in active PD patients. METHODS: VEGF levels were determined in serum and
      plasma, and in peritoneal effluent (PE) after 4, 8 and 15 h dwell times. RESULTS:
      PE VEGF levels were 58.6+/-33.7 pg/mL, with a mean VEGF D/P ratio of 0.45+/-0.29
      (range 0.06-0.93). In low-transport patients (n = 7) this ratio did not differ
      from high-average ones (n=5) (0.48+/-0.3 and 0.41+/-0.1, NS). In multivariate
      analysis, the VEGF D/P ratio showed no correlation with the independent variables
      included in this study. VEGF levels were higher in 15 h than in 8 h effluent; so
      the VEGF D/P ratios were higher as well. Regression analysis showed a direct
      correlation between PEVEGF levels and dwell time (r: 0.57, p = 0.03), but not
      between VEGF D/P ratio and dwell time. PEVEGF levels directly correlated with
      effluent protein content. Regression analysis showed no correlation between
      PEVEGF levels and age, time on PD, days of peritonitis, urea and creatinine-mass
      transfer coefficients, ultrafiltration capacity, and accumulated glucose dose.
      Multivariate regression analysis showed correlation only between PEVEGF levels
      and dwell time, but not with the other independent variables. CONCLUSIONS: This
      study confirms that VEGF is present in fresh PE from PD patients at levels that
      suggest local production and filtration from plasma. Peritoneal effluent VEGF
      levels are not significantly associated with peritoneal functional parameters and
      background, and seem to be influenced by ultrafiltration in a dilution process.
      We believe that the role of VEGF in peritoneal pathophysiology is part of a
      complex relationship involving multiple peritoneal structures and other growth
      factors, including local counteracting factors for VEGF that regulate
      neoangiogenesis.

PMID- 11506250
TI  - The impact of bleeding times on major complication rates after percutaneous real
      time ultrasound-guided renal biopsies.
AB  - BACKGROUND: Previous studies have shown that bleeding times have positive
      predictive values of only 5% for perioperative bleeding in unselected
      populations. Nevertheless, performing bleeding times prior to all renal biopsies
      is common in nephrology practice. METHODS: We report complications of 112 renal
      biopsies done at Walter Reed Army Medical Center (WRAMC) from 1996-99 performed
      without preceding bleeding times. Renal biopsies were done only on normotensive
      (<140/90) patients who had not recently been taking aspirin or non-steroidal anti
      inflammatory agents, under real-time ultrasound guidance with automated 16 g
      (WRAMC) spring-loaded guns. High-risk patients (with serum creatinine > or = 3
      mg/dl or creatinine clearance < or =30 cc/min by Cockroft-Gault formula, N=18,
      16%) at WRAMC were treated with pre-renal biopsy estrogens or DDAVP. Factors were
      tested for their association with complications after renal biopsy using Chi
      Square testing for categorical variables and student's t-test for continuous
      variables. A stepwise logistic regression model was used to test for independent
      significance of factors. RESULTS: There were two cases each of gross hematuria
      and inadequate tissue (1.8% each). There were no transfusions or deaths. In
      univariate analysis, male gender and lower serum creatinine level at time of
      biopsy were significantly associated with increased risk of complications after
      biopsy. However, these factors were not significant in logistic regression
      analysis. CONCLUSION: This study suggests that the use of bleeding times does not
      significantly alter the major complication rates associated with percutaneous
      real-time ultrasound guided renal biopsy.

PMID- 11506251
TI  - IgA nephropathy: multivariate statistical analysis aimed at predicting outcome.
AB  - BACKGROUND: Several risk factors of IgA nephropathy (IgAN) have been identified,
      but their importance in predicting outcome is still controversial. METHODS: We
      conducted a retrospective study on 119 patients (pts) with IgAN. All had a follow
      up of over five years (mean 134+/-56 months). For each patient we recorded age,
      24h proteinuria, hematuria, renal function (RF), arterial hypertension (AH) and
      histological features. Multivariate analysis was done for predictive purposes
      (segmentation, using Chi-squared Automatic Interaction Detection-CHAID). RESULTS:
      AH at the time of renal biopsy was the principal and independent predicting
      factor: 30/50 (60%) hypertensive pts had serum creatinine > or =1.5 mg/dL at the
      end of follow-up compared to 9/69 (13%) pts with normal blood pressure. Age was a
      further predictive parameter: 21/28 (75%) pts with AH and age over 39 years had
      reduced RF at the last examination. In this subgroup, 18/19 (95%) with evidence
      of tubulo-interstitial lesions showed a decline of RF. CONCLUSIONS: AH and age
      alone are significant prognostic factors; tubulo-interstitial lesions are an
      additional pointer to poor outcome in these pts. The algorithm obtained with
      segmentation analysis may be a guideline for prognosis in single patients with
      IgA nephropathy.

PMID- 11506252
TI  - Renal involvement in subjects with peripheral atherosclerosis.
AB  - BACKGROUND: Ischemic nephropathy is an important cause of renal failure in
      western countries. Subclinical renal function abnormalities may exist in patients
      with extrarenal atherosclerosis, and may precede the onset of overt ischemic
      nephropathy. METHODS: To assess the impact of extrarenal atherosclerosis on the
      kidney, we evaluated renal function in 89 subjects with differing degrees of
      peripheral atherosclerosis, without manifest clinical or laboratory signs of
      ischemic nephropathy and renovascular hypertension. All laboratory testing,
      ultrasonography with Doppler analysis for the localization of peripheral vascular
      disease (carotid and lower limb arteries), and non-invasive evaluation of renal
      function by radionuclide studies of renal plasma flow (MAG3 clearance) and
      glomerular filtration (DTPA clearance), as well as total, LDL and HDL
      cholesterol, and triglycerides were determined; smoking habit was recorded. By
      combining sonographic data on arterial tree stenosis (ATS), the subjects were
      grouped according to the atherosclerotic vascular damage (ATS involvement).
      RESULTS: Despite no change in plasma creatinine and DTPA clearance (from 91.58+/
      26.53 mL/min/1.73 m2 to 93.47+/-24.82), MAG3 clearance progressively declined
      with the severity of vascular damage (from 244.86+/-60.60 mL/min/1.73 m2 to
      173.59+/-58.74). Stepwise multiple regression analysis indicated that MAG3
      clearance was best explained by ATS involvement (standardized beta coefficient 
      0.40; p<0.001), smoking habit (-0.34; p= 0.004), and serum LDL-cholesterol (
      0.24; p<0.035). CONCLUSIONS: The renal hemodynamic profile in atherosclerotic
      patients might constitute functional evidence of the silent phase of ischemic
      renal disease. The findings suggest that renal function should be carefully
      assessed in patients with extrarenal atherosclerosis, particularly in those with
      classic cardiovascular risk factors.

PMID- 11506253
TI  - Pentosidine, carotid atherosclerosis and alterations in left ventricular geometry
      in hemodialysis patients.
AB  - OBJECTIVE: To assess the relationship between advanced glycation end products
      (AGE) and cardiovascular damage in end-stage renal diseases. METHODS: Ninety-one
      hemodialysis patients who had been on dialysis treatment for at least six months
      were recruited for the study. Each patient underwent echocardiography and an echo
      color Doppler study of the carotid arteries. We measured plasma pentosidine and
      related it to intima media thickness, atherosclerotic plaques and parameters of
      left ventricular geometry. RESULTS: Pentosidine was higher in patients treated by
      low-flux dialysis (31.0+/-16.6 pmol/mg protein) than in those treated by high
      flux dialysis (25.4+/-7.6 pmol/mg protein), but this difference was of marginal
      statistical significance (P=0.08). On multivariate analysis, plasma IgG
      (beta=0.24, P=0.02) was the only independent correlate of plasma pentosidine.
      Intima media thickness and the number of atherosclerotic plaques were unrelated
      to plasma pentosidine. Mean wall thickness (beta=0.18, P<0.05), relative wall
      thickness (beta=0.20, P<0.05) and left ventricular end-diastolic volume (beta= 
      0.23, P<0.01) were independently related to plasma pentosidine. CONCLUSIONS:
      Pentosidine, a reliable marker of "carbonyl stress", is unrelated to intima media
      thickness and to the number of atherosclerotic plaques, but it is related to
      alterations in heart geometry. These data suggest that the effect of carbonyl
      stress on the cardiovascular system is complex and that the effects of AGE on the
      heart may be dissociated from those on the arterial system.

PMID- 11506254
TI  - Kaposi's sarcoma in a patient with focal glomerulosclerosis.
AB  - We report the clinical features and outcome af a patient who presented Kaposi's
      sarcoma following immunosuppressive therapy for FGS; Cyclophosphamide and
      steroids were administered; the patient recovered after three months treatment
      with i.v. vinblastine.

PMID- 11506255
TI  - Successful therapy combined with surgery for severe post-transplant nocardiosis.
AB  - We report a case of a 35-year-old man with nocardiosis infection involving soft
      tissue and the central nervous system who had received a cadaveric donor kidney.
      The patient was admitted with fever, malaise and right shoulder pain. Soft tissue
      abscess was seen on ultrasound examination. It was presumed due to gram (+)
      microorganisms, so 4 g day (IV) ampicillin/sulbactam was started empirically once
      the abscess was drained. Nocardia asteroides was found in the pus specimen. On
      the second day in hospital, severe headache, ataxia and signs of meningeal
      irritation appeared. The cranial CT showed two intracranial abscesses in the
      frontal lobe and cerebellum. We assumed Nocardia asteroides was the infective
      agent for the cerebral abscesses, so antibiotic therapy was switched to
      trimethoprim-sulphamethox-asole (3x160/800 mg/d). Nausea and vomiting occurred on
      the fifth day of therapy, improving after drainage from the frontal abscess.
      However, these complaints recurred five days later. CT showed cerebellar abscess
      had become bigger. The patient's complaints improved after the second surgical
      drainage. N. asteroides was again grown in the aspiration fluids of both cerebral
      abscesses. Complete regression of the abscesses was seen in the CT after two
      months. Co-trimoxazole was continued for six months then withdrawn. Graft
      dysfunction was not observed. Early medical and surgical interventions may be
      life-saving in this potentially lethal disease.

PMID- 11506256
TI  - Henoch-Schonlein purpura after 20 years of renal replacement therapy.
AB  - While the clinical impact of the impaired immune response, commonly described in
      chronic dialysis patients, is still a matter of discussion, it is usually
      considered that immunological diseases tend to become progressively less active
      after the start of regular renal replacement therapy (RRT). We reported a case of
      Henoch-Schonlein Purpura in a 51-year-old male, on RRT for 20 years, 8 on
      dialysis and 12 with renal graft, because of ESRD of unknown origin (chronic
      glomerulonephritis?). The acute onset of the syndrome, presenting purpuric rash,
      abdominal discomfort and asymmetric joint pain with edema and local signs of
      acute inflammation, was followed by several relapses over a 2 years period. This
      biopsy proven diagnosis offered an explanation for his chronic renal failure;
      furthermore, we conclude that, possibly because of the usually good correction of
      uremic immunodepression by efficient dialysis (this patient's Kt/V ranged from
      1.1 to 1.3 according to Lowrie's formula), the possibility of immune diseases
      should be carefully considered even in long long-term RRT patients.

PMID- 11506257
TI  - Severe preeclampsia in antithrombin III deficiency with no history of venous
      thromboembolism.
AB  - Complications of pregnancy, such as preeclampsia, placental abruption, fetal
      growth retardation, still-birth and fetal death are associated with an increased
      frequency of pro-thrombotic abnormalities. We describe a case of severe
      preeclampsia and multiple placental infarctions in a 28-year-old woman at 31
      weeks' gestation. Despite a negative personal history for venous thromboembolism,
      coagulation screening for thrombophilia detected an isolated antithrombin III
      deficiency. In view of the high prevalence of pro-thrombotic complications,
      laboratory screening for thrombophilia would be advantageous in women with
      complicated pregnancies, to ensure adequate management in high-risk situations,
      as suggested by larger-scale clinical investigations.

PMID- 11506258
TI  - Renal abnormalities in Mayer-Rokitanski-Kuster-Hauser syndrome.
AB  - Mayer-Rokitanski-Kuster-Hauser (MRKH) syndrome, is a rare disorder characterized
      by the congenital absence of the uterus and vagina. The prevalence has been
      reported as one in 4000-5000 female births. Patients with MRKH syndrome have a
      46.XX karyotype and normal secondary sex characteristics. The external genitalia
      appear normal, but only a shallow vaginal pouch is present. Ovarian function is
      normal. A 54-year-old woman came to our observation for the treatment of arterial
      hypertension. Her history involved primary amenorrhea and sterility. She had
      undergone abdominal and pelvic sonography as a routine screening and they had
      shown the absence of the uterus, left renal agenesis and a contralateral pelvic
      kidney. These findings were confirmed by urography and CT scan of the abdomen.
      Gynecologic examination showed a small vaginal pouch (2 cm). Thus, the diagnosis
      of MRKH syndrome with associated congenital anomalies of the upper urinary tract
      was made for the first time in this lady at the age of 54 years. Associated
      congenital anomalies of the upper urinary tract are reported to occur in 30-40%
      of all cases of MRKH syndrome. No specific figures are available on what
      percentage of women with missing kidney might also have MRKH syndrome. However,
      in 40-50% of patients with renal agenesis, an associated genital anomaly has been
      found. In conclusion, this report is intended to remind our community of the
      existence of congenital renal abnormalities associated with gynecologic
      abnormalities, a field of nephrology usually amply neglected.

PMID- 11506259
TI  - The validity of adult arrestee self-reports of crack cocaine use.
AB  - Despite the many problems associated with crack use, little validated empirical
      evidence about the prevalence of crack cocaine exists. Researchers that track
      crack cocaine use have relied on self-reports to differentiate crack and powder
      cocaine. Prior research suggests that the accuracy of self-reports for the use of
      a variety of illicit substances is relatively low. To examine the validity of
      self-reports of crack use, this article employs a newly developed technology to
      detect specifically the presence of markers of crack cocaine in urine specimens.
      With a sample of 2327 arrestees from six cities that participate in the Arrestee
      Drug Abuse Monitoring (ADAM) Program, both face-to-face interview and urinalysis
      data were examined. Using a positive urinalysis result as the validity standard,
      we assessed the extent to which arrestees underreport crack cocaine use as
      compared to the use of marijuana, opiates,and methamphetamine. Logistic
      regression models were also de veloped to predict the factors that relate to
      underreporting. The results showed a considerable amount of underreporting for
      all the drug measures. In most cases, only about half the people who had a
      positive urinalysis test for drugs admitted using drugs. Overall, the least
      amount of underreporting occurred for the use of marijuana (63.6% told the
      "truth"), followed by methamphetamine (56.1% told the truth), crack (48.2% told
      the truth), and opiate (45.9% told the truth). Female crack users, as compared to
      male crack users, were more likely to admit using crack. Black arrestees were
      more likely to admit using crack than white or Hispanic arrestees. Arrestees with
      a history of prior drug treatment or a prior arrest, as compared to those without
      such histories, were more likely to admit using crack. The older the arrestee
      was, the more likely the arrestee would admit using crack. The more money an
      arrestee spent on drugs, the more likely the arrestee would admit using crack.
      Differences in underreporting were also observed across the six cities in this
      study. The implications of these findings for the monitoring of crack use are
      discussed.

PMID- 11506260
TI  - Comorbidity of psychiatric and substance use disorders in late adolescence: a
      cluster analytic approach.
AB  - Cluster analysis was used to identify subgroups of youths with past-year
      substance and/or psychiatric disorders (N = 110, mean age 19.0 years). Data for
      this study came from a community-based, prospective longitudinal investigation of
      speech/language (S/L) impaired children and matched controls who participated in
      extensive diagnostic and psychosocial assessments at entry into the study at 5
      years of age and again at follow-up. Clustering variables were based on five DSM
      diagnostic categories assessed at age 19with the University of Michigan Composite
      International Diagnostic Interview. Using Ward's method, the five binary
      variables were entered into a hierarchical cluster analysis. An iterative
      clustering method (K-means) was then used to refine the Ward solution. Finally, a
      series of analyses of variance (ANOVAs) were run to analyze group differences
      between clusters on measures of Global Assessment of Functioning (GAF), criminal
      involvement, anxiety and depressive symptomatology, and frequency of drug use and
      heavy drinking. The analysis yielded eight replicable cluster groups, which were
      labeled as follows: (a) anxious (20.9%); (b) anxious drinkers (5.5%); (c)
      depressed (16.4%); (d) depressed drug abusers (10%); (e) antisocial (16.4%); (f)
      antisocial drinkers (10%); (g) drug abusers (8.2%); (h) problem drinkers (12.7%).
      These groups were differentiated by external criteria, thus supporting the
      validity of our cluster solution. Cluster membership was associated with a
      history of S/L impairment: A large proportion of the depressed drug abusers and
      the antisocial cluster group had S/L impairment that was identified at age 5.
      Clarification of the developmental progress of the youths in these cluster groups
      can inform our approach to early intervention and treatment.

PMID- 11506261
TI  - Concurrent substance use and outcome in combined behavioral and naltrexone
      therapy for opiate dependence.
AB  - The effect of concurrent nonopiate drug use on outcome of treatment for opiate
      dependence. METHOD: Forty-seven opiate-dependent patients received a 6-month
      course of outpatient treatment with naltrexone and cognitive-behavioral therapy
      (behavioral naltrexone therapy, BNT) at a university-based research clinic.
      Opiate-negative urines and naltrexone ingestion were rewarded with monetary
      vouchers. Abstinence from other drugs was encouraged verbally, but no
      contingencies were placed on nonopiate drug use. The proportions of all urines
      (collected twice weekly) positive for cocaine, cannabis, and benzodiazepines over
      the course of treatment were evaluated as predictors of outcome of opiate
      dependence treatment, as measured by proportion of opiate-positive urines, days
      retained in treatment, and proportion of naltrexone doses taken, using Pearson
      product moment correlations and one-way analysis of variance (ANOVA). RESULTS:
      The majority of patients (78%) used a nonopiate drug at least once during the
      trial. There were no significant correlations between concurrent drug use
      measures and opiate dependence treatment outcomes, indicating no simple linear
      relationship between these measures. However, when concurrent drug use was
      trichotomized into abstinent, intermittent, and heavy use groups, groups with
      intermittent use had superior outcome compared to both abstinent and heavy use
      groups in several contrasts. CONCLUSIONS: Intermittent use of nonopiate drugs is
      common during outpatient treatment for opiate dependence and may be a favorable
      prognostic indicator. This may support a "harm reduction" approach as opposed to
      a strict abstinence-oriented approach. Further research is needed to identify the
      optimal therapeutic stance toward other drug use during treatment for opiate
      dependence.

PMID- 11506262
TI  - Antisocial behavioral syndromes and return to drug use following residential
      relapse prevention/health education treatment.
AB  - This study compared residential addiction treatment clients meeting full DSM-III
      R criteria for antisocial personality disorder (ASPD) with those reporting
      syndromal levels of antisocial behavior only in adulthood (AABS) on time to and
      severity of first posttreatment drug use. Antisocial syndrome and selected other
      mental disorders were assessed using the Diagnostic Interview Schedule, Revised
      for DSM-III-R, and validity of self-reported posttreatment drug behavior was
      measured against results of hair analysis. Among subjects followed within 180
      days after treatment exit, individuals with ASPD were at modestly increased risk
      of a first lapse episode compared to those with AABS. However, the two groups did
      not differ in severity of lapse. Participants with ASPD demonstrated poorer
      agreement between self-reported posttreatment drug behavior and hair data. These
      results add to the evidence suggesting that the DSM requirement for childhood
      onset in ASPD may be clinically important among substance abusers in identifying
      a severely antisocial and chronically addicted group at elevated risk for early
      posttreatment recidivism. Our findings support the importance of careful
      classification of antisocial syndromes among substance abusers and the
      identification of characteristics of these syndromes that underlie clients' risks
      for posttreatment return to drug use to provide optimally individualized
      treatment planning.

PMID- 11506263
TI  - Influence of an educational program on medical students' attitudes to substance
      use disorders in pregnancy.
AB  - Substance use disorders (SUDs) in pregnancy are becoming increasingly prevalent.
      Our study aimed to measure the effect of a teaching module on alcohol, tobacco,
      and drug use on the attitude of second year medical students toward pregnant
      women with SUDs. A questionnaire was administered to 84 medical students before a
      5-week systems block on human reproduction, which included specific learning
      events related to SUDs. The questionnaire was readministered at the completion of
      the block. Pre- and postintervention scores were compared. Students showed
      significant improvement (p < .05, reliability coefficient 0.90) in their level of
      comfort in dealing with womenwith SUD in pregnancy. Other positive trends
      relating to attitudes toward drug- and alcohol-dependent women during pregnancy
      were also identified. SUD teaching interventions among medical students can
      improve their comfort level and attitude toward pregnant women with SUDs. This
      supports the current initiative of Project CREATE (Curriculum Renewal and
      Evaluation of Addiction Training and Education) to implement a comprehensive
      undergraduate SUD teaching program in Canadian medical schools.

PMID- 11506264
TI  - HIV testing in the setting of inpatient acute substance abuse treatment.
AB  - We examined patients' attitudes toward HIV testing in the setting of acute
      substance abuse treatment and determined the prevalence of offering routine on
      site testing for human immunodeficiency virus (HIV) in inpatient state-funded
      detoxification centers in New England. Voluntary questionnaires were administered
      to patients (N = 66 respondents) at the only two state-funded inpatient drug
      detoxification treatment centers in Rhode Island, and a telephone survey of all
      state-funded inpatient detoxification facilities across the New England area was
      conducted. In New England, 17/38 (44.7%) of all state-funded inpatient
      detoxification facilities didnot routinely offer on-site HIV testing to clients.
      Of participants, 97% responded positively to the question, "Do you think HIV
      testing should be available to patients in drug detoxification facilities such as
      this one?" There were 89% who reported that they would cope "about the same" or
      "better" with receiving a positive HIV test result while in detoxification
      treatment versus elsewhere. The greatest number of participants ranked the
      Orasure HIV test, an assay for HIV-1 transmucosal antibody, as the test they
      would most prefer while in drug treatment. However, 59% of patients responded
      that the type of test offered would not make a difference in whether they chose
      testing. Most patients indicated that they would want to see a physician within a
      few days of a positive diagnosis of HIV infection. Despite the controversy
      surrounding the provision of HIV testing to patients in inpatient acute substance
      abuse treatment, HIV testing is desired among these patients provided that HIV
      clinical care is readily available.

PMID- 11506266
TI  - Nicotine replacement methods on a psychiatric unit.
AB  - Patients with psychiatric illness smoke more heavily than others in the
      community. They have more difficulty quitting and have more withdrawal symptoms
      than others. OBJECTIVE: The purpose of the present study was to examine the
      utilization of nicotine replacement methods in a population of psychiatric
      patients. METHOD: In a naturalistic retrospective review, we examined the records
      of 55 patients who were hospitalized on a smoke-free psychiatric unit. We
      abstracted the frequency of utilization of nicotine replacement. The rate of
      utilization was considered a ratio of the number of days utilized to the number
      of days prescribed. RESULTS: There were 38 patients (69%) who used the
      transdermal patch, 26 patients (47%) used the inhaler, 4 patients (7%) used
      nicotine gum, and 2 patients (4%) used the nasal spray. The rate of utilization
      of the nicotine inhaler (63%) exceeded that of the transdermal nicotine patch
      (30%) (t = 4.6, p < .0001). CONCLUSION: The hospitalization of smokers with
      mental illness in smoke-free psychiatric units often leads to further behavioral
      deterioration. The patients in the present study demonstrated a definite
      preference for the nicotine inhaler over the transdermal patch. Possible clinical
      and pathophysiological implications of this finding are discussed.

PMID- 11506265
TI  - Lowering HIV risk among ethnic minority drug users: comparing culturally targeted
      intervention to a standard intervention.
AB  - To test the efficacy of culturally targeted acquired immunodeficiency syndrome
      (AIDS) prevention programs on ethnic minority street drug users, 669 African
      American and Puerto Rican drug users were assigned to receive either the National
      Institute on Drug Abuse (NIDA) standard intervention or a culturally competent
      enhanced intervention in a quasi-experimental study. The standard intervention
      was a two-session educational program, while both the African-American and Puerto
      Rican enhanced interventions provided additional AIDS information in a culturally
      appropriate fashion. Although human immunodeficiency virus (HIV) risk behaviors,
      as measured by Bell's risk indices, decreased, there were no meaningful
      significant differences between interventions. However, participants who went
      into drug treatment programs showed greater reduction in HIV risk behavior.
      Cultural interventions may provide better outcome if they concentrate on getting
      participants into drug treatment.

PMID- 11506267
TI  - Relationships between drinking problems and drinking locations among convicted
      drinking drivers.
AB  - This study examines relationships between drinking problems and the frequency of
      drinking in eight types of places within a sample of convicted drinking drivers.
      Drinking problems were measured by two instruments, the Mortimer-Filkins
      Questionnaire (MFQ) and the Alcohol Use Disorders Identification Test (AUDIT)
      Core Questionnaire. Data were collected from convicted drinking drivers who were
      ordered by the court to attend the Mississippi Alcohol Safety Education Program
      (MASEP). Both the MFQ and the AUDIT were found to be more strongly related to the
      frequency of drinking in moving automobiles than to the frequency of drinking in
      any other type of place. This suggests that drinking drivers with severe drinking
      problems are more likely to drink in moving automobiles than are those with less
      severe problems. The strong linkage between severe alcohol problems and drinking
      in automobiles has important implications with respect to highway safety.

PMID- 11506268
TI  - General and job-related alcohol use and correlates in a municipal workforce.
AB  - We examined the prevalence and correlates of both general and workplace-related
      drinking measures using data from a telephone survey of 673 workers in a large
      municipal bureaucracy and tested the hypothesis that observed differences across
      job categories can be explained by compositional difference in terms of
      demographic variables known to be related to drinking behavior. Results suggest
      such factors account for much of the variation in general drinking measures
      (prior-28-day quantity, CAGE score, indicating risk for dependence), but that
      significant variation in a workplace-related drinking measure (times ever drank
      before, during, or just after work) remains even after such factors are
      controlled. Implications of these findings for existing theories of workplace
      effects on drinking are discussed, along with a consideration of appropriate
      levels of analysis for future studies.

PMID- 11506269
TI  - Pharmacological aversion treatment of alcohol dependence. I. Production and
      prediction of conditioned alcohol aversion.
AB  - Eighty-two hospitalized alcoholics receiving pharmacological aversion therapy
      (PAT) over a 10-day treatment interval completed cognitive, behavioral, and
      psychophysiological measures evaluating conditioned aversion to alcohol. Pre-post
      assessments provided convergent support for the efficacy of PAT vis-a-vis
      production of conditioned aversion to alcohol. Positive alcohol-related outcome
      expectancies were significantly reduced, whereas confidence that drinking could
      be avoided in various high-risk situations for consumption was increased
      following PAT. Behavioral and cardiac rate assessments revealed significant
      changes following PAT that were specific to alcoholic beverages and potentially
      reflective of conditioned alcohol aversion. Patients with more extensive
      pretreatment experiences with alcohol-associated nausea and greater involvement
      in antisocial conduct appeared to be less susceptible to the PAT conditioning
      protocol.

PMID- 11506270
TI  - Preventing alcohol-related problems at the University of Arizona's homecoming: an
      environmental management case study.
AB  - In 1995, the University of Arizona installed and publicized new policies to
      provide better alcohol control during its annual homecoming event. Systematic
      observation at pregame tents revealed that, compared to 1994, these policies led
      to a lower percentage of tents selling alcohol, elimination of beer kegs, greater
      availability of food and nonalcoholic beverages, the presence of hired bartenders
      to serve alcohol, and systems for identification checks. These changes were still
      in evidence through 1998. In 1995, campus police also saw a downward shift in the
      number of neighborhood calls for complaints related to homecoming activities,
      which was maintained through 1998. Statistics on law enforcement actions were
      inconsistent. There was a sharp drop in 1995, but 1996 and 1998 saw enforcement
      levels similar to what was seen prior to the new policies. This case study
      underscores the importance of environmental management strategies for campus
      based alcohol and other drug prevention.

PMID- 11506271
TI  - Fluorescence polarization assay for the diagnosis of brucellosis: a review.
AB  - Fluorescence polarization assay (FPA) is based on the rotational differences
      between a small soluble antigen molecule in solution (labelled with a
      fluorochrome) and the antigen molecule complexed with its antibody. A small
      molecule will rotate randomly at a rapid rate, resulting in rapid depolarization
      of light, while a larger complex molecule will rotate slower and depolarize light
      at a reduced rate. The rate change in depolarization can be measured. The FPA is
      a homogeneous assay which does not require removal of unreacted reagents and can,
      therefore, be performed very quickly and, given portable equipment, in the
      laboratory and in the field. The latter obviates the need for shipping samples
      and eliminates waiting for results, as well as reducing test costs. The FPA
      technology has been developed and validated for the serological diagnosis of
      brucellosis in cattle, swine, sheep, goats, bison, and cervids. Sufficient cross
      reactivity of the common epitopes of Brucella abortus, B. melitensis and B. suis
      O-polysaccharide (OPS) allowed for the use of a single antigen for all species of
      smooth Brucella and animals. The OPS prepared from B. abortus S1119.3 was
      conjugated with fluorscein isothiocyanate (FITC). The FPA was initially developed
      for testing serum; however, the technology has been extended to testing whole
      blood and milk from individual animals or bulk tank samples pooled from 2000 or
      fewer animals. The accuracy of the FPA equalled or exceeded those obtained using
      other serological tests such as the buffered antigen plate agglutination test
      (BPAT), the milk ring test (MRT), the complement fixation test (CFT), the
      indirect enzyme immunoassay (IELISA), and the competitive enzyme immunoassay
      (CELISA).

PMID- 11506272
TI  - Validation of the fluorescence polarization assay for detection of milk antibody
      to Brucella abortus.
AB  - A fluorescence polarization assay (FPA) for detection of antibody to Brucella
      abortus in individual milk samples was developed and validated. Samples from 190
      cattle from which B. abortus was isolated; milk samples from cattle in herds
      infected with B. abortus (n = 1,086) and positive in the milk ring test (MRT), as
      well as milk samples from Canadian cattle (with no evidence of brucellosis, n =
      2,974) were tested by the indirect enzyme immunoassay (IELISA) and the FPA. The
      sensitivity (based on samples from culture positive cattle) and specificity
      (based on Canadian milk samples) of the IELISA and the FPA were 100%. The
      relative sensitivity value obtained with milk from cattle of infected herds and
      the specificity values of the IELISA were 98.5 and 99.9%, respectively. The
      relative sensitivity and specificity of the FPA with the same samples were 82.2
      and 99.4% using a cutoff value of 90 millipolarization units (mP). The low
      relative sensitivity value of the FPA was shown, by competitive enzyme
      immunoassay (CELISA), to be due to vaccinal antibody (assumed as vaccinal
      antibody against B. abortus Sl19 is excluded by the FPA and CELISA but not by the
      MRT and the IELISA), present in some of the milk samples. The FPA is a
      homogeneous assay which, unlike the MRT and the IELISA, may be used for testing
      in the field.

PMID- 11506273
TI  - On-line immunoaffinity extraction followed by high-performance liquid
      chromatography and radioimmunoassay for a novel retinobenzoic acid, AM-80, in
      human plasma.
AB  - On-line coupled immunoaffinity chromatography and reversed-phase high performance
      liquid chromatography (on-line IAC-HPLC) with detection by radioimmunoassay (RIA)
      was developed for 4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)
      carbamoyl] benzoic acid (Am-80) in human plasma. A 0.05-mL sample was directly
      loaded onto an immunoaffinity pre-column packed with immobilized polyclonal
      antibodies against Am-80. The immunoaffinity extract was then automatically
      introduced to reversed-phase

PMID- 11506274
TI  - IL-6 secretion by ex vivo whole blood cultures upon allergen stimulation.
AB  - Allergen induced IL-6 synthesis by whole blood cultures was compared with skin
      prick allergen test results for the same group of individuals. Whole blood
      cultures from both allergic and non-allergic individuals secrete IL-6 at high
      allergen concentrations. When whole blood cultures from controls were incubated
      with serial dilutions of allergens it was found that IL-6 induction was abolished
      at lower allergen dilutions (allergen threshold concentration or ATC). When whole
      blood cultures from patients with allergic rhinitis were stimulated with ATC it
      was found that some allergens induced IL-6 secretion. The allergens inducing IL-6
      and the level of IL-6 secreted were dependent on the patient. The induction of IL
      6 secretion by the cultures at ATC correlated very significantly with the
      patient's skin prick test results (r = 0.71 1; p = 0.0003).

PMID- 11506275
TI  - Improved antibody coating protocol using a second antibody antiserum. Application
      to total thyroxin immunoassay.
AB  - A complete antibody coating protocol for the preparation of dry antibody coated
      tubes is presented. This protocol is based on a recently described antibody
      immobilization principle. We modify this immobilization principle in order to
      improve and simplify the coating procedure. In addition, we propose a drying
      procedure that provides long-term storage stability of the antibody coated tubes.
      According to the modified protocol, polystyrene plastic tubes are first coated
      with rabbit gamma-globulins. The tubes are incubated with a sheep anti-rabbitIgG
      antiserum dilution. After incubation, antigen-specific antibody antiserum raised
      in rabbits is added directly into the tubes containing the sheep anti-rabbit IgG
      antiserum solution (difference from the original protocol). Finally, the tubes
      are washed, blocked, and dried following the drying procedure developed. The
      suitability of the modified protocol for the development of immunoassays
      requiring high loading of antibody was exemplified through the development of a
      RIA for total thyroxin. The estimated assay characteristics (detection limit 4
      microg/L, dynamic range up to 210 microg/L, within-run CV 2.7-5.7%, between-run
      CV 5.1-7.3%, recovery 84.4-112%, cross-reactivity for T3 1.9%) were comparable
      with those provided by commercially available RIA kits for the determination of
      thyroxin.

PMID- 11506276
TI  - A fully automated microscope bacterial enumeration system for studies of oral
      microbial ecology.
AB  - A fast and fully automated image analysis technique for the enumeration of
      fluorescence-labeled bacteria in oral sampleswas developed. This paper describes
      the system configuration, application strategy, automated operation, and initial
      validation experiments using fluorescent microspheres, bacterial cultures, in
      vitro grown biofilms and human dental plaque. Following a series of brief
      operator-controlled calibration steps, the technique automatically performs all
      necessary microscope operations (stage translation, focus, sampling and analysis)
      on slides with up to 48 wells for as many different samples. It quantifies
      bacteria from differential interference contrast images, images showing cells
      that had been labeled by immunofluorescence with monoclonal antibodies, or images
      with cells labeled by a fluorescent DNA stain. With all evaluated samples, close
      agreement between the automated system and the assessor's visual counts was
      observed. This novel automated image grabbing and analysis procedure is
      applicable to the enumeration of specific taxa in clinical samples by both
      immunofluorescence and fluorescent in situ hybridization.

PMID- 11506277
TI  - Stress protein CSP 310 causes oxidation and phosphorylation uncoupling during low
      temperature stress only in cereal but not in dycotyledon mitochondria.
AB  - It was found that an addition of antiserum obtained against stress protein 310 kD
      increased coupling of oxidation and phosphorylation in mitochondria isolated from
      cold-stress winter rye shoots and had no influence on dycotiledon mitochondria
      (pumpkins and sunflower). The data obtained showed a difference between molecular
      weights of dycotyledon polypeptides with immunochemical affinity to CSP 310 and
      CSP 310 subunits. It was shown that low-temperaturestress caused a transition to
      a low-energy state ("cold uncoupling") of free from endogenous free fatty acid
      cereal mitochondria. At the same time, this "cold uncoupling" in mitochondria of
      dycotyledon species investigated was not detected. We suppose that a special
      mechanism of low-temperature stress reaction in mitochondria dealing with
      uncoupling activity of stress protein CSP 310 exists in cereals.

PMID- 11506278
TI  - Validation of an ELISA for the quantitation of human complement receptor 1.
AB  - An ELISA was developed and validated for the quantitation of Complement Receptor
      1 (CR1) in human plasma. The ELISA employed a monoclonal anti-CR1 antibody
      adsorbed onto microtiter plates to capture CR1 in human plasma. The captured CR1
      was treated with a detecting antibody which had a different epitopic specificity
      for CR1. HRP conjugated anti IgG (secondary antibody) was used for quantitation.
      The standard curve covered a wide range from 10 pg to 800 pg. The inter- and
      intra-assay variation were found to be low and within the acceptable limits.
      Specificity and accuracy for the assay was established by ensuring negligible
      cross reactivity with other proteins and an excellent parallelism between the
      sample and standard curve. The samples were checked for loss of sCR1 levels
      through freeze/thaw cycles at different intervals of time stored at -70 degrees
      C.

PMID- 11506280
TI  - Practical limitations of prescribing stress as an anti-aging treatment.

PMID- 11506279
TI  - Applying hormesis in aging research and therapy.
AB  - Biology of aging is well understood at a descriptive level. Based on these data,
      biogerontological research is now able to develop various possibilities for
      intervention. A promising approach for the identification of gerontogenes and
      gerontogenic processes is through the hormetic effects of mild stress on slowing
      down aging. Although there are several issues remaining to be resolved, specially
      with regard to the notion of mild stress, application of hormesis in aging
      research and therapy is a powerful new approach.

PMID- 11506281
TI  - Hormesis, aging and longevity determination.

PMID- 11506282
TI  - Hormesis extends the correlation between stress resistance and life span in long
      lived mutants of Caenorhabditis elegans.

PMID- 11506283
TI  - Applying hormesis in aging research and therapy: a sensible hope?

PMID- 11506284
TI  - Hormesis--a new hope for ageing studies or a poor second to genetics?

PMID- 11506285
TI  - Comments to paper by S. Rattan: applying hormesis in aging research and therapy-
      a perspective from evolutionary biology.
AB  - The phenomenon of hormesis is discussed from an evolutionary biology perspective,
      i.e. in a context of fitness. Some of the evolutionary theories of aging are
      outlined. The influence of associations between traits and their environmental
      specificity is highlighted. Questions about consistency of the impact of hormetic
      agents across life stages are raised and finally the uniformity of definitions
      across disciplines is shortly discussed.

PMID- 11506286
TI  - Applying hormesis in aging research and therapy: a commentary.

PMID- 11506287
TI  - Hormesis: a quest for virtuality?

PMID- 11506288
TI  - Hormesis and aging.

PMID- 11506289
TI  - Hypercarcinogenic state in chronic liver disease.

PMID- 11506290
TI  - Alcohol-induced asthma.

PMID- 11506291
TI  - Pathogenesis of hemorrhagic cerebral infarction.

PMID- 11506292
TI  - Glomerulopathy in MELAS syndrome.

PMID- 11506293
TI  - Amebiasis in acquired immunodeficiency syndrome.

PMID- 11506294
TI  - Angiogenesis factors.
AB  - Angiogenesis is a recent highlight in the medical field; the developmental
      process and pathological conditions for various diseases can be understood from
      the novel aspect of "angiogenesis". Many angiogenesis-related factors are
      involved in the development of vessels during embryogenesis (vasculogenesis), as
      well as the induction of new vessels in response to physiological or pathological
      stimuli. In particular, the appearance of hemangioblasts, precursor cells for
      vascular endothelial cells and blood cells, and blood islands are expected to
      play a "prelude" role in tubulogenesis. Gene knock out mice of vascular
      endothelial growth factor (VEGF)/VEGF receptor, ephrin-B2, and angiopoietin-1
      results in a failure of normal vessels production. Dormant factors derived from
      proteolytic cleavage of various physiological substrates are expected to balance
      a homeostasis of "angiogenic states" in the host. Furthermore, angiogenesis under
      various pathological conditions of malignant tumors, ocular diseases, psoriasis,
      rheumatoid arthritis, atherosclerosis and other diseases is associated with
      complex angiogenesis networks, suggesting pleiotropic mechanisms for
      angiogenesis.

PMID- 11506295
TI  - Aldosterone as a mediator of progressive renal dysfunction: evolving
      perspectives.
AB  - End-stage renal disease (ESRD) comprises an enormous public health burden, with
      an incidence and prevalence that are increasingly on the rise. This escalating
      prevalence suggests that newer therapeutic interventions and strategies are
      needed to complement current therapeutic approaches. Although much evidence
      demonstrates conclusively that angiotensin II mediates progressive renal disease,
      recent evidence also implicates aldosterone as an important pathogenetic factor
      in progressive renal disease. Recently, several lines of experimental evidence
      demonstrate that selective blockade of aldosterone, independent of renin
      angiotensin blockade, reduces proteinuria and nephrosclerosis in the
      spontaneously hypertensive stroke-prone rat (SHRSP) model and reduces proteinuria
      and glomerulosclerosis in the subtotally nephrectomized rat model (ie, remnant
      kidney). Whereas pharmacologic blockade with angiotensin II receptor blockers and
      angiotensin-converting enzyme (ACE) inhibitors reduces proteinuria and
      nephrosclerosis/glomerulosclerosis, selective reinfusion of aldosterone restores
      these abnormalities despite continued renin-angiotensin blockade. Aldosterone may
      promote fibrosis by several mechanisms, including plasminogen activator inhibitor
      1 (PAI-1) expression and consequent alterations of vascular ribrinolysis, by
      stimulation of transforming growth factor-beta1 (TGF-beta1), and by stimulation
      of reactive oxygen species (ROS). Based on this formulation, randomized clinical
      studies will be initiated to delineate the potential renal-protective effects of
      aldosterone receptor blockade.

PMID- 11506296
TI  - Elevated plasma homocysteine concentrations six months after gastroplasty in
      morbidly obese subjects.
AB  - OBJECTIVE: To investigate whether the increased homocysteine levels occur in the
      first 6 months postoperatively, when nutritional intake is the most inadequate
      and weight reduction is the most drastic. PATIENTS AND METHODS: Fasting glucose,
      insulin, lipoprotein, homocysteine, folic acid and vitamin B12 levels and oral
      glucose, tolerance test (OGTT) were determined in 12 morbidly obese subjects (3
      men and 9 women with a mean age of 31+/-3 years, mean+/-SEM) before, 6 and 12
      months after banded gastroplasty. RESULTS: Gastroplasty resulted in significant
      weight loss, from 120+/-6 to 92+/-6 and 88+/-7 kgs, 6 and 12 months
      postoperatively (all p<0.001). Fasting plasma insulin and triglyceride
      concentrations, the ratio of total cholesterol to HDL cholesterol, glucose and
      insulin responses to OGTT, and the degree of insulin resistance as expressed by
      the Homeostasis model index decreased significantly (p<0.05-0.001) following
      gastroplasty. Fasting plasma homocysteine concentrations increased from 10.2+/
      0.8 to 12.1+/-0.6 at 6 months (p=0.036) and 12.0+/-1.2 micromol/l at 12 months
      (p=0.040), respectively. Pooled plasma homocysteine levels were negatively
      correlated with serum folate concentrations (r=-0.42, p=0.013). However, serum
      folate and vitamin B12 levels did not change after gastroplasty, nor did the
      relation between the loss of body weight and increase in homocysteine levels.
      CONCLUSION: We observed that elevated circulating homocysteine levels occurred as
      early as 6 months after gastroplasty despite improvement in carbohydrate and
      lipoprotein metabolism in morbidly obese Chinese subjects.

PMID- 11506297
TI  - Long-term prognosis after recovery from myocardial infarction: a community-based
      survey in Yamagata, Japan.
AB  - OBJECTIVE: To assess the long-term prognosis after recovery from acute myocardial
      infarction (AMI) in the general population in Japan. PATIENTS AND METHODS: Among
      the 575,000 inhabitants of the Yamagata metropolitan area, a total of 117
      patients suffered from first their AMI from April to December 1993. Thirteen
      patients (11%) died within four weeks after the onset. Of the remaining 104
      patients, 101 (mean age, 69+/-12 years) were followed for an average of 65+/-5
      months. RESULTS: Twenty-seven of the 101 patients (27%) died during the follow-up
      period. Compared with survivors, the patients who died were significantly older
      at the onset of AMI (74+/-12 vs. 67+/-12 years, p<0.01). More diabetic patients
      than non-diabetic patients died (42 vs. 21%, p<0.05) because of the higher
      frequency of non-cardiac deaths (29 vs. 11%, p<0.05). The total number of deaths
      of cardiac origin, including sudden deaths, was 11 (40%) and was lower than the
      number of definite non-cardiac deaths (n=15). The time from the onset of AMI to
      death was significantly shorter in cases of cardiac death than in cases of non
      cardiac death (median, 16 vs. 45 months, p<0.01). Among non-cardiac deaths,
      deaths due to lung cancer and cerebral infarction were notable in men
      (standardized mortality ratio 278) and women (571), respectively. CONCLUSION: Non
      cardiac death during long-term follow-up after AMI was more frequent than death
      of cardiac origin. Thus, preventive measures, including early treatment of
      complicating diseases, must be implemented to improve the long-term prognosis of
      patients with myocardial infarction.

PMID- 11506298
TI  - Elevated serum myosin light chain I in influenza patients.
AB  - OBJECTIVE: Myocarditis has been described as a complication of influenza.
      Patients with influenza may have symptoms and abnormal laboratory data (including
      chest X-ray, electrocardiogram, etc.) suggestive of myocarditis, although few
      observations have been made regarding the prevalence of asymptomatic myocardial
      injury. We investigated whether influenza can produce myocardial injury without
      cardiac symptoms. METHODS: During the epidemic of influenza A (H3N2) from 1998 to
      1999 in Japan, we examined possible cardiac muscle damage associated with
      influenza in patients without apparent clinical myocardial injury by measuring
      serum myosin light chain concentrations. PATIENTS: Ninety-six influenza-positive
      patients (46 males and 50 females, average age 43.4 years) without impaired renal
      function were studied. RESULTS: Of these patients, 11 (11.4%) had elevated serum
      myosin light chain I concentrations. CONCLUSION: Asymptomatic myocardial injury
      may be present in patients with influenza even when they have no symptoms
      suggestive of myocardial injury.

PMID- 11506299
TI  - Analysis of lupus activity in end-stage renal disease treated by hemodialysis.
AB  - OBJECTIVE: The activity of systemic lupus erythematosus (SLE) has been reported
      to decrease in patients who have developed end-stage renal disease (ESRD).
      However, extrarenal symptoms attributable to the disease activity are noted,
      especially during the first year of dialysis. We studied the clinical course and
      evaluate the disease activity of SLE in patients with ESRD on hemodialysis for
      more than 6 months. SUBJECT AND METHODS: Fourteen patients with SLE who had been
      initiated on maintenance dialysis at our center between 1982 and 1999 were
      examined retrospectively. Their clinical details, organ system manifestations,
      serologic profiles and immunosuppressive treatment regimens were reviewed.
      Patients with and without postdialysis flaras of SLE were compared statistically.
      RESULTS: Five patients exhibited 6 SLE flares under treatment with
      corticosteroids. Two flares occurred within the first year of the initiation of
      dialysis, and in 1 patient, aggravation of the disease activity was noted 98
      months after the initiation of dialysis. Polyarthritis was noted in 5 cases and
      fever in 4 cases. The serum complement levels decreased in all 6 cases with
      relapse of SLE activity. Compared with the other 9 patients who did not exhibit
      SLE relapse, no significant differences were found in 5 patients who did with
      respect to the demographic and serologic features at the initiation of dialysis.
      CONCLUSION: We conclude that the disease activity does not always burn out in
      patients of SLE who show progression to ESRD. SLE flares can sometimes occur even
      after one year of the initiation of dialysis. SLE patients on dialysis should be
      carefully followed up by clinical and serological monitoring, and treated by
      appropriate immunosuppressive therapy.

PMID- 11506300
TI  - Carboplatin calculated with Chatelut's formula plus etoposide for elderly
      patients with small-cell lung cancer.
AB  - OBJECTIVE: This dose escalation was conducted to evaluate the applicability of
      Chatelut's dosing, and to determine the efficacy and toxicity of carboplatin with
      etoposide in previously untreated elderly patients (>70 years) with small cell
      lung cancer. PATIENTS AND METHODS: Seventeen patients were treated with etoposide
      for 3 days and carboplatin calculated dose using Chatelut's formula on day 1
      intravenously. The starting doses of etoposide on days 1 to 3, and carboplatin
      using the area under the concentration versus time curve (AUC) were 90 mg/m2 and
      4 mg/ml x min, respectively. RESULTS: The median age was 77 years (range 71 to
      87). Dose-limiting toxicity (DLT) was seen at level 4 (AUC 5 mg/ml x min of
      carboplatin and etoposide 100 mg/m2). Hematologic toxicity was the primary DLT.
      Grade 4 thrombocytopenia and Grade 4 leukopenia were observed at level 4. Non
      hematologic toxicity was insignificant. The overall response rate was 94%.
      CONCLUSION: Etoposide at 100 mg/m2 and AUC of carboplatin of 4.5 mg/ml x min as
      calculated using Chatelut's formula every four weeks is the recommended dose for
      further phase II trials for elderly patients with small cell lung cancer.

PMID- 11506301
TI  - Development of interferon-alpha resistant subline from human chronic myelogenous
      leukemia cell line KT-1.
AB  - OBJECTIVE: Interferon-alpha (IFN-alpha) is one of the most effective therapeutic
      agents for a number of hematological malignancies, including chronic myelogenous
      leukemia (CML). Nevertheless, its efficacy is limited because of the development
      of resistance to IFN-alpha therapy. Previously, we established the novel human
      CML cell line KT-1, which is sensitive to the antiproliferative effects of IFN
      alpha. Here, we report the establishment of an IFN-alpha-resistant subline, KT
      1/A3R alpha 1000, by culturing KT-1/A3 cells (IFN-alpha-sensitive subline of KT
      1) with increasing concentrations of IFN-alpha, in order to analyze the mechanism
      of acquisition of IFN-alpha resistance in CML cells after IFN-alpha therapy.
      SUBJECTS AND METHODS: We developed an IFN-alpha-resistant tumor cell variant, KT
      1/A3R alpha 1000, from the KT-1/A3 cell line by culturing cells with increasing
      concentrations of IFN-alpha. This subline was examined for its ability to
      proliferate and its resistance to apoptosis in high concentrations of IFN-alpha.
      The induction of the ISGF3 complex in response to IFN-alpha alpha in KT-1/A3R
      alpha 1000 was compared with that in the parental cell. RESULTS: The levels of
      interferon-stimulated gene factor 3 components (STAT1, STAT2, and p48) proteins
      and STAT2 tyrosine phosphorylation induced after IFN-alpha treatment were
      unchanged, but formation of the ISGF3 complex was remarkably reduced in KT-1/A3R
      alpha 1000 cells compared to parental cells. CONCLUSION: The KT-1/A3R alpha 1000
      subline is a useful model for studying the mechanism of IFN-alpha resistance
      after IFN-alpha therapy.

PMID- 11506302
TI  - Myelitis associated with atopic disorders in Japan: a retrospective clinical
      study of the past 20 years.
AB  - OBJECTIVE: To clarify the clinical features of myelitis associated with atopic
      disorders in Japanese patients. SUBJECTS AND METHODS: We retrospectively studied
      the clinical, immunological and electrophysiological features of 68 consecutive
      patients with myelitis of acute or subacute onset diagnosed at Kyushu University
      Hospital during the past 20 years. RESULTS: While only 2 of 28 (7%) patients with
      myelitis diagnosed between 1979 and 1993 had either atopic dermatitis (AD) or
      bronchial asthma (BA), 19 of 40 (48%) patients with myelitis diagnosed between
      1994 and 1998 did. Among the 40 patients with myelitis diagnosed between 1994 and
      1998, 19 patients with either AD or BA as well as 21 patients without either
      disease showed a significantly higher level of serum total IgE, higher frequency
      of hyperIgEaemia and higher frequency of mite antigen-specific IgE than 82
      healthy controls. Myelitis patients with AD presenting as persistent
      paresthesia/dysesthesia in all four limbs showed cervical cord lesions on MRI and
      abnormalities in upper limb motor evoked potentials but no abnormalities in the
      cerebrospinal fluid (CSF), while myelitis patients with BA showed preferential
      involvement of the lower motor neurons clinically and electromyographically. In
      addition, 12 patients with myelitis who had hyperIgEaemia and mite antigen
      specific IgE but neither AD nor BA showed incomplete transverse myelitis with
      mild motor disability and few CSF abnormalities. CONCLUSION: The clinical
      features of myelitis associated with atopic disorders were in part distinguished
      by the type of preceding atopic disorder, and also were different from those of
      hyperIgEaemic myelitis with no preceding atopic disorders.

PMID- 11506303
TI  - Unilateral bronchiectasis and esophageal dysmotility in congenital adult
      tracheoesophageal fistula.
AB  - Tracheoesophageal fistulas (TEF) in adults are most commonly neoplastic, and very
      rarely congenital in nature. We report a 45-year-old Hispanic male with TEF and
      initial presentation of minimal hemoptysis. The patient had radiographic evidence
      of unilateral upper lobe (RUL) bronchiectasis, massive esophageal dilatation, and
      dysmotility. However, there was no evidence of esophageal malignancy, achalasia,
      or Chagas' disease. Bronchoscopy revealed a large TEF in the posterior wall of
      trachea, which was not visualized on esophagram or esophagoscopy. Bronchoalveolar
      lavage (BAL) cultures grew Mycobacterium avium complex (MAC). Our report
      illustrates that idiopathic, or congenital, TEF can be associated with esophageal
      dysmotility, adulthood bronchiectasis, and atypical mycobacterial superinfection.

PMID- 11506304
TI  - Heterochronous development of intrahepatic cholangiocellular carcinoma following
      hepatocellular carcinoma in a hepatitis B virus carrier.
AB  - A 68-year-old Japanese woman was admitted to our hospital in September 1995,
      because of a mass detected by ultrasonography during a follow-up examination for
      chronic hepatitis B. Hepatocellular carcinoma (HCC) in the right liver lobe was
      diagnosed based on imaging studies and elevated alpha-fetoprotein (AFP).
      Percutaneous ethanol injection therapy (PEIT) was performed. PEIT was repeated in
      November 1998, because the tumor had enlarged and serum AFP was re-elevated.
      Follow-up ultrasonography (US) demonstrated low echoic mass in the left liver
      lobe in August 1999; serum AFP was normal, but serum carbohydrate antigen 19-9
      (CA19-9) was elevated to 420 U/ml. In October 1999, radiofrequency interstitial
      tissue ablation (RITA) was performed after tumor biopsy. Pathological findings
      revealed adenocarcinoma and pathological diagnosis was made as intrahepatic
      cholangiocellular carcinoma (ICC). Three weeks later, her serum CA19-9 was
      remarkably decreased (180 U/ml). The patient has been well for 5 months. Her
      latest AFP and CA19-9 in the serum were 2 ng/ml and 89 U/ml, respectively. The
      incidence of double cancer in the liver is rare. This is also the first case
      report to discuss ICC treated with RITA.

PMID- 11506305
TI  - Primary adenosquamous carcinoma of the liver which produces granulocyte-colony
      stimulating factor and parathyroid hormone related protein: association with
      leukocytosis and hypercalcemia.
AB  - A 55-year-old man was admitted to our hospital with fever and vomiting. Abdominal
      computed tomography (CT) revealed multiple low density masses in the liver. A
      diagnosis of primary adenosquamous carcinoma of the liver was confirmed by
      histological examination of a necropsy specimen. The present case showed
      leukocytosis and hypercalcemia with high levels of serum granulocyte-colony
      stimulating factor (G-CSF) and parathyroid hormone related protein (PTHrP).
      Recent studies have shown that G-CSF and PTHrP are responsible for the
      paraneoplastic syndromes with leukocytosis and hypercalcemia. The tumor cells
      demonstrated positive cytoplasmic immunohistochemistry staining with anti-G-CSF
      and anti-PTHrP antibodies. This result suggested that the tumor produced G-CSF
      and PTHrP.

PMID- 11506306
TI  - Hyperbaric oxygen for anorexia nervosa.
AB  - Hyperbaric oxygen was given to a patient with anorexia nervosa who had developed
      postoperative ileus, resulting in not only improvement in ileus, but also
      enhancement of intestinal movement, inducing the feeling of hunger, and thereby
      increasing food ingestion. Hyperbaric oxygen may be effective as an initial
      treatment for anorectic patients showing severe bloating and resistance to food
      ingestion.

PMID- 11506307
TI  - Pheochromocytoma of the urinary bladder revealed with cerebral hemorrhage.
AB  - The case was a 51-year-old man, who has been undergoing treatment with oral
      medication for hypertension for three years. The patient was admitted to the
      author's clinic for hemorrhage in the left putamen. He was diagnosed as having
      primary pheochromocytoma of the bladder from such symptoms as paroxysmal blood
      pressure elevation after urination, mild increase in catecholamine levels before
      and after urination, and from the results of 131I-MIBG scintigraphy, and
      cystoscopy, and underwent excision of the bladder tumor. Upon endocrinological
      examination, only mild increases in catecholamine levels were found. Therefore,
      constant monitoring of blood pressure and 131I-MIBG scintigraphy were useful for
      a definitive diagnose.

PMID- 11506308
TI  - Acute severe alcohol-induced bronchial asthma.
AB  - We report the case of a severe bronchial asthma attack 15 minutes after the
      ingestion of food containing small amounts of alcohol. Although an ethanol
      inhalation test was negative, an acetaldehyde inhalation test was positive.
      Furthermore, it was discovered that the patient was homozygous for a mutation of
      the aldehyde dehydrogenase-2 (ALDH-2) gene. We subsequently diagnosed his attack
      as acute severe alcohol-induced asthma. Since bronchial asthma patients who are
      homozygous for mutant ALDH-2 genes are susceptible to acute severe alcohol
      induced asthma attacks, strict clinical attention is thought a necessity.

PMID- 11506309
TI  - Bilateral massive pleural effusions caused by uremic pleuritis.
AB  - A 61-year-old man was started on hemodialysis in June 1998. Just after the
      commencement of dialysis, a chest X-ray film revealed bilateral pleural
      effusions. The effusions were hemorrhagic and exudative, and did not respond to
      dialysis. He was transferred to our university hospital on October 8,1998.
      Repeated thoracentesis demonstrated hemorrhagic and exudative characteristics
      without any diagnostic evidence. Pleural biopsies showed fibrosis and lymphocyte
      infiltration. The effusions were massive and did not respond to treatments
      including hemodialysis, repeatedly performed pleurodesis and the administration
      of antituberculous drugs. He died of respiratory failure on December 30, 1998.
      The autopsy confirmed bilateral fibrinous pleuritis without any underlying
      infections or malignancy. We diagnosed this case as uremic pleuritis from this
      clinical course and the autopsy findings. The clinical entity of uremic pleuritis
      was recognized as a complication of patients with hemodialysis in 1969. Uremic
      pleuritis generally responds to continued hemodialysis and the prognosis is
      usually good. However, some case reports demonstrated that surgical decortication
      is only indicated in cases with a severe clinical course. The clinical course of
      the present case was progressive and fatal. Uremic pleuritis is a serious
      complication of hemodialysis, which may lead to death.

PMID- 11506310
TI  - Primary racemose hemangioma of the bronchial artery.
AB  - A 44-year-old woman was admitted to our hospital for repeated hemoptysis.
      Selective angiography of the bilateral bronchial arteries showed them to be
      enlarged and convoluted, and revealed shunts between the bronchial and pulmonary
      arteries. The patient was diagnosed as having racemose hemangioma of the
      bronchial artery. Although embolization of the bronchial artery with gelatin
      sponges was performed, hemoptysis emerged again about one year later. Finally,
      segmentectomy of the right lower lung was performed and primary racemose
      hemangioma of the bronchial artery was histopathologically confirmed.

PMID- 11506311
TI  - Bacillus cereus brain abscesses occurring in a severely neutropenic patient:
      successful treatment with antimicrobial agents, granulocyte colony-stimulating
      factor and surgical drainage.
AB  - Multiple brain and liver abscesses developed immediately after Bacillus cereus
      bacteremia in a neutropenic patient with acute lymphoblastic leukemia. After even
      8 weeks of antimicrobial chemotherapy together with administration of granulocyte
      colony-stimulating factor, every infectious process disappeared but the patient's
      headache has still persisted. Because the wall of one brain abscess became thin
      and was in danger of rupturing into the ventricle, surgical drainage was
      performed, resulting in disappearance of headache and resolution of brain
      abscess. The present case indicates that a combined medical and surgical approach
      is mandatory to treat patients with brain abscesses.

PMID- 11506312
TI  - Massive pontine hemorrhagic infarction associated with embolic basilar artery
      occlusion.
AB  - We report here an autopsy case of massive pontine hemorrhagic infarction
      secondary to embolic basilar artery occlusion. A large embolus appeared to have
      traversed the vertebral artery into the basilar artery as a result of
      basilarization of the vertebral artery due to severe stenosis of the
      contralateral vertebral artery. Extensive ischemia due to embolic occlusion of
      the entire length of the basilar artery, and migration of the embolus are assumed
      to have resulted in a massive pontine hemorrhagic infarction.

PMID- 11506313
TI  - An autopsy case of mitochondrial encephalomyopathy with lactic acidosis and
      stroke-like episodes syndrome with chronic renal failure.
AB  - A 25-year-old man developed a stroke-like episode. He suffered from renal failure
      and became dialysis-dependent. His mother was also dialysis-dependent. A3243G
      point mutation of the mitochondrial tRNA(leu) gene was detected in both of them.
      The patient was diagnosed with mitochondrial encephalomyopathy with lactic
      acidosis and stroke-like episodes (MELAS), and died of a recurrence of stroke
      like episodes at the age of 30. Autopsy revealed numerous abnormal mitochondria
      in the kidneys, but no renal vascular changes. This is the first report of a
      MELAS case in which the presence of numerous abnormal mitochondria in podocytes
      and tubules was confirmed by electron microscopy.

PMID- 11506314
TI  - Generalized Wegener's granulomatosis responding to sulfamethoxazole-trimethoprim
      monotherapy.
AB  - Wegener's granulomatosis (WG) has two different clinical phases: the initial
      phase and generalized phase. In patients with generalized WG, both steroids and
      cyclophosphamide have generally been used. We report a case of generalized WG
      that was temporarily, but successfully treated with sulfamethoxazole-trimethoprim
      (S/T) alone. S/T therapy reduced the elevated levels of soluble IL-2 receptor and
      IL-6 in parallel with improvement of the patient's symptoms and urinary protein
      excretion. In view of the high incidence of lethal adverse effects of cytotoxic
      drugs, S/T monotherapy may be worth trying not only for initial phase WG but also
      for generalized WG with careful follow-up when the patient is not acutely ill.

PMID- 11506316
TI  - Evolving concepts in breast reconstruction with latissimus dorsi flaps: results
      and follow-up of 121 consecutive patients.
AB  - Breast reconstruction using autologous tissue is increasingly gaining in
      interest. A review of results obtained from a series of consecutive patients
      undergoing breast reconstruction with the latissimus dorsi flap (LDF) was carried
      out to evaluate the effects of the authors' refinements to the procedure. Data
      collected during the perioperative course and a minimum follow-up of 12 months in
      121 patients (mean age, 47 years; 50% with previous radiotherapy) who underwent
      treatment from 1994 to 1998 were analyzed retrospectively. In addition, a
      structured interview was conducted to evaluate patient satisfaction. Eighteen
      different surgeons in one teaching hospital were involved in the operative
      procedures. No patient was referred to the intensive care unit. An additional
      implant was used in 25% of patients. With the exception of the occurrence of
      seroma, the complication rate was low (seroma, 60%; bleeding, 4%; hematoma, 5%;
      minor wound dehiscence, 3%; wound infection, 2%). No flap was lost. Donor site
      morbidity was extremely low; 90% of patients had no complaints. The result of
      surgery was rated as excellent or good by 59% of patients, 89% would undergo this
      type of breast reconstruction again, and 91% would recommend it to other women.
      Refinements that improved the technique substantially included incision lines
      exclusively in the bra line, improved flap volume resulting from the harvest of
      an extended fat pad, and quilting sutures to reduce the formation of seroma. In
      the current study, endoscopic muscle harvest did not represent an improvement in
      procedure. The technique of breast reconstruction with the LDF has been improved
      substantially during the past few years, and provides the plastic surgeon with an
      excellent, safe, and consistently successful method for breast reconstruction.

PMID- 11506315
TI  - Amebiasis in Japanese homosexual men with human immunodeficiency virus infection.
AB  - We report cases of amebiasis in 6 human immunodeficiency virus (HIV)-positive
      male patients. Five were confirmed homosexuals while one was suspected. Three
      patients had liver abscess and 5 had colitis with duration of 10 days to months.
      The patients with liver abscess showed a lower incidence of abdominal pain but a
      higher incidence of concomitant diarrhea. Drainage therapy was effective for
      rapid afebrile results. Two invasive colitis cases died from perforation. This
      may have been due to delayed diagnosis. Invasive amebiasis is not common even in
      HIV-infected individuals. Among Japanese homosexual men, however, it may cause
      symptomatic diseases.

PMID- 11506317
TI  - Liposuction as an adjunct procedure in reduction mammaplasty.
AB  - Liposuction has been recognized as a useful adjunct to breast reduction surgery
      for fine contouring of adjacent areas to achieve aesthetic balance and
      preservation of nipple sensation. In particular, the liposuction technique has
      provided an acceptable way of treating the "fat roll" of the lateral portion of
      the breast, which extends to the axilla and lateral chest. The purpose of this
      study was to review the authors' approach to adjunctive lipoplasty with breast
      reduction surgery and to review their experience. Examination of their own
      results in 70 consecutive women who underwent reduction mammaplasty in 1998 by
      the senior surgeon did not reveal any substantial difference in the complication
      rate of those women who had adjunctive liposuction with their breast reduction
      surgery vs. those who did not. All complications such as fat necrosis,
      cellulitis, and seromas were confined to the breast and were not related to the
      liposuction. Furthermore, there was no additional morbidity associated with
      ultrasonic liposuction compared with traditional suction-assisted lipectomy.
      Their experience indicates that patients undergoing reduction mammaplasty may
      benefit aesthetically from adjunct lateral chest wall liposuction without
      additional morbidity.

PMID- 11506318
TI  - Results of cranial vault reshaping.
AB  - This study was designed to assess the outcome of cranial vault reshaping for
      correction of deformity of the skull and the upper face. A retrospective review
      of all children who underwent cranial vault reshaping by a single team of
      surgeons between 1993 and 1996 was performed. There were 10 children in the
      series. The age at surgery ranged from 6 to 62 months (mean age, 25 months). Five
      children in the series had untreated sagittal craniosynostosis with
      scaphocephaly, two had pansynostosis resulting in cloverleaf skull deformity, and
      three had turricephaly after shunt treatment of hydrocephalus. There was no
      operative mortality. Blood loss ranged from 250 to 1,500 ml (mean, 422 ml). All
      patients needed transfusion. There were two major complications resulting from
      increased intracranial pressure, but both patients recovered completely with no
      neurological sequelae. Titanium plates and screws were used in all patients, but
      were removed in two when they became palpable. The 5 children with sagittal
      craniosynostosis had a normal head shape. The 2 children with cloverleaf skull
      have improved head shape with persistent increased bitemporal width and round
      faces. The 3 children with turricephaly after shunting have marked improvement
      with mild persistent deformity. This study shows that cranial vault reshaping is
      safe and can lead to a long-term normal head shape in children with late
      correction of sagittal craniosynostosis. Children with more severe anomalies,
      particularly syndromic patients, can be improved but will have persistent mild
      deformity.

PMID- 11506319
TI  - Cross-foot island instep flap: a new use of instep skin flap for management of
      persistent wounds after complex plantar foot reconstruction.
AB  - When presented with an extensive soft-tissue defect involving the sole of the
      foot, reconstruction with free muscle flaps covered by a split-thickness skin
      graft is the proposed method of treatment. However, persistent graft breakdown
      and a chronic wound of the weight-bearing flap is a challenging problem during
      the late postoperative period, as experienced by the authors in their patients
      with high-energy-induced lower extremity injuries. The authors used the instep
      flap as an island cross-foot flap to manage persistent graft breakdown that
      involved skin-grafted muscle flaps transferred previously to the heel in 3
      patients and to treat a chronic wound involving an amputation stump in 1 patient.
      The vascular pathology of the injured extremities indicated a cross-leg procedure
      instead of a free flap transfer. Pedicles were wrapped with split-thickness skin
      grafts and flaps were harvested superficial to the plantar fascia. Pedicles were
      divided during postoperative week 3, and no complications related to the
      operation or to immobilization have been encountered during the postoperative
      follow-up. During the 1-year follow-up, durable coverage, free from development
      of open wounds, has been achieved, and patients have expressed their
      satisfaction. In the case of complicated, high-velocity foot injuries, the
      authors suggest that this procedure be kept in mind as an alternative treatment
      option because it has some advantages over conventional cross-leg procedures.

PMID- 11506320
TI  - Nonendoscopic harvest of the gastrocnemius muscle flap through a small incision.
AB  - Traditional gastrocnemius flap harvest requires a long skin incision, starting
      from the popliteal fossa to the mid leg. The authors designed three instruments
      to facilitate harvest of this flap through a small incision without the help of
      an endoscope in 10 patients. All 10 gastrocnemius muscle flaps survived with a
      100% success rate.

PMID- 11506321
TI  - Development of a clinically useful mechanical leech device that promotes flap
      survival in an animal model of venous-congested skin flaps.
AB  - The authors describe the design and testing of a mechanical leech device that has
      shown greater efficacy in alleviating venous congestion and promoting skin flap
      survival than previously described clinical therapies. Abdominal skin flaps (3 x
      6 cm) were raised on Sprague-Dawley rats and were subjected to two ischemic
      events that simulated clinical venous congestion. The animals received two
      treatments with the device prototype during 7-day experiment (N = 9). Flap
      perfusion was monitored with a scanning laser Doppler imager (LDI) and was
      normalized to adjacent skin perfusion. Photographic images of flaps at 7 days
      were assessed for areas of nonnecrotic tissue, and LDI data consisted of
      perfusion measurements at nine time points during the 7-day experiment. The
      device prototype was able to promote an average survival area in the flap of 60.0
      +/- 3.5%, which was not only a significant (p < 0.05) increase over previously
      published control groups (8.0 +/- 5.0%) that did not receive any treatment, but
      was a significant increase over the same treatment schedule with clinically used
      leeches (34.6 +/- 7.3%). At 7 days, LDI data showed flap perfusion to be 65.6 +/-
      7% of adjacent skin perfusion, a significant increase over this level at the end
      of the second ischemic event (21 +/- 1%; p < 0.05). These results suggest that
      this device could be used clinically to alleviate venous congestion and to
      promote flap survival. The device could also be useful for prophylactic
      treatments and to minimize treatment delays because its long shelf-life permits
      immediate availability when a treatment decision is made.

PMID- 11506322
TI  - Vascular resistance in human muscle flaps.
AB  - Important differences in free muscle flap survival have been reported in the
      setting of long arterial and venous vein grafts. The authors provide insight into
      the etiology of flap failure by addressing the following question: Do differences
      in flap type result in clinically significant different vascular resistances and
      consequently anastomotic patency? A total of 15 human flaps were studied
      intraoperatively: 9 gracilis, 3 rectus abdominis, and 3 latissimus dorsi. The
      muscle was isolated on a single pedicle and hemodynamic stability was ensured.
      The venous pedicle was then divided. A timed collection of effluent was used to
      determine flow. Vascular resistance was calculated by dividing the change in
      pressure by the flow, and standardizing this for temperature and hematocrit.
      Average vascular resistance and standard deviation for the gracilis, rectus, and
      latissimus flaps was 10.34 +/- 7.77 mmHg per milliliter per minute, 2.79 +/- 1.50
      mmHg per milliliter per minute, and 3.17 +/- 1.05 mmHg per milliliter per minute
      respectively. An inverse relationship between muscle vascular resistance and flap
      mass was found (p < 0.001). This indicates that larger muscles have less vascular
      resistance. The decreased resistance gives rise to higher flow rates and, as a
      result, potentially improved vein graft patency. The clinical implication is that
      a larger flap should be used when high flow-through is critical. The role of flap
      vascular territory makeup continues to be pursued.

PMID- 11506323
TI  - Experimental model of pyridoxine (B6) deficiency-induced neuropathy.
AB  - A pyridoxine (B6) dietary deficiency was studied in female adult Sprague-Dawley
      rats by hind-limb walking-track analysis. Serum levels of pyridoxine and three
      metabolites were quantified by high-pressure liquid chromatography with
      fluorescence measurement. Morphometric analysis of the sciatic and posterior
      tibial nerves (from within the tarsal tunnel) was performed after 1 year on a
      diet deficient in vitamin B6. The B6-deficient rats developed abnormal walking
      track patterns by 8 months, and these track parameters were different from age-
      and sex-matched normal diet control rats at the p < 0.05 level. Adding B6 at 10
      parts per million to the diet then partially corrected these parameters, whereas
      the addition of 30 parts per million B6 corrected the abnormal pattern
      completely. Serum pyridoxal concentration correlated with the functional
      parameters, dropping from a mean of 115 mg per liter to 39.5 mg per liter (p <
      0.05), and correcting with the B6 additive. Morphometric analysis demonstrated
      that the B6-deficient nerve from the tarsal tunnel had a decreased nerve fiber
      density (p < 0.001), with a normal total myelinated nerve fiber number, and an
      increased axon-to-myelin ratio (p < 0.003). It is concluded that a diet totally
      deficient in vitamin B6 results in a peripheral neuropathy.

PMID- 11506324
TI  - A new flap model in rats: iliac osteomusculocutaneous flap.
AB  - Although osteomusculocutaneous flaps are used frequently in clinical practice to
      repair defects involving soft tissue and bone, there are still many questions
      that remain to be answered regarding their basic physiology. To accomplish such
      basic science studies, simple and reliable animal osteomusculocutaneous flap
      models are needed. The purpose of this study was to describe a new flap model in
      rats--namely, the iliac osteomusculocutaneous flap. Thirty adult Wistar rats
      weighing 200 to 250 g were used in this experiment. In 15 rats, the vascular
      anatomy of the iliolumbar vessels and their relation with adjacent soft tissues
      and the iliac bone was determined by anatomic dissection. Based on this anatomic
      study, the iliac osteomusculocutaneous flap model was created in rats. The flap
      is comprised of a skin island (3 x 3 cm) in the flank region, a 1 x 1-cm segment
      of iliac bone, and an abdominal wall muscle cuff. In 10 rats, the flap was raised
      as an island flap based on its vascular pedicle of iliolumbar vessels, and was
      replaced in situ. In the remaining 5 rats, the flap was transferred to the groin
      region as a free flap. Direct observation on postoperative day 7 revealed that
      the skin island of all the flaps was completely viable. Bone scintigraphy
      performed on postoperative day 3 in free flaps demonstrated radionuclide uptake,
      indicating viability of the bony segment. The dye injection study revealed ink
      staining within blood vessels of the bone, confirming its viability.
      Microangiography of the flap demonstrated vascularity of each component of the
      flap by the iliolumbar vessels, including a distinct branch to the iliac bone.
      The authors conclude that the iliac osteomusculocutaneous flap of the rat is a
      simple and reliable flap model that offers the following advantages: (1) It is a
      true osteomusculocutaneous flap, (2) it can be used as a free flap without the
      need for an isogeneic rat, (3) the vascular pedicle is consistent, and (4) it is
      harvested from a small-animal species.

PMID- 11506325
TI  - The effect of trimetazidine on the survival of rat island skin flaps subjected to
      ischemia-reperfusion injury.
AB  - The effect of trimetazidine (TMZ) on flap ischemia-reperfusion injury was
      investigated in rat inferior epigastric artery flaps. Twenty-six rats, divided
      into four experimental groups-nonischemic group (group 1, N = 5), ischemic
      control group (group 2, N = 7), preischemic TMZ-treated group (group 3, N = 7),
      and postischemic TMZ-treated group (group 4, N = 7)-were used. Rat inferior
      epigastric artery flaps were rendered ischemic by occluding the feeding femoral
      artery, and they were reperfused by releasing the clamps after 11 hours in groups
      2 through 4. Group 3 rats were given TMZ (3 mg per kilogram, intravenously)
      diluted in saline before application of the clamp, and group 4 rats were given
      TMZ before clamp removal. Flap survival was scored on postoperative day 8. All
      flaps in the nonischemic control group (group 1) survived completely. The
      ischemic control group (group 2) demonstrated a 6.3 +/- 4.3% survival area. In
      the preischemic TMZ group (group 3) the mean survival area was 76.9 +/- 6.1%, and
      in the postischemic TMZ group (group 4) it was 76.8 +/- 5.6%. TMZ-treated flaps
      showed a significant increase in survival area regardless of the time of
      administration (p = 0.001, group 3 vs. group 2; p = 0.001, group 4 vs. group 2).
      This finding suggests that TMZ has a beneficial effect on the prevention or
      treatment of arterial ischemic flaps.

PMID- 11506326
TI  - The prognostic importance of c-myc oncogene expression in head and neck melanoma.
AB  - Melanomas of the head and neck have a poorer prognosis than melanomas arising at
      other cutaneous sites. To study the biology of this disease, the expression of
      the c-myc oncogene was studied in tumors from 97 patients with head and neck
      melanoma using the technique of flow cytometry. Survival analysis revealed that
      stratification of patients according to oncogene expression provided a prognostic
      marker with shorter overall survival in tumors with high nuclear c-myc
      oncoprotein positivity (log-rank test, chi2 = 8.77, p < 0.005). Multifactorial
      analysis using Cox's proportional hazards model revealed nuclear c-myc
      oncoprotein to be an independent prognostic marker (log-rank test, chi2 = 8.82, p
      = 0.005). These results support the authors' previous studies of the prognostic
      value of c-myc expression in melanoma and suggest that estimation of c-myc
      oncoprotein may be of clinical importance in identifying high-risk patients.

PMID- 11506327
TI  - Detection of E-cadherin expression after nerve repair in a rat sciatic nerve
      model.
AB  - The authors investigated E-cadherin expression during nerve regeneration after
      nerve suture using the rat sciatic nerve model. Five rats were used during each
      postoperative period. E-cadherin expression was detected by Western blot analysis
      and immunofluorescent staining with an anti-E-cadherin monoclonal antibody. The
      level of E-cadherin expression was calculated as the amount relative to that
      found in normal control nerve. The level of E-cadherin expression was decreased
      at first, and then gradually increased. The maximum level of E-cadherin was 1.92
      +/- 0.07 fold in the sutured nerve. The level of E-cadherin expression in the
      sutured nerve was significantly greater (p < 0.0001) than that of the normal
      control nerve from postoperative day 3 to 21, and that of sutured nerve returned
      to the control level by postoperative day 28. The immunofluorescent staining
      results indicated that E-cadherin expression was almost negative or decreased
      immediately after the operation, but the degree of expression increased gradually
      in Schwann's cells. The degree of E-cadherin expression was significantly greater
      than that of normal control nerves from postoperative day 7 to 14, and returned
      to the control level by postoperative day 21. These results demonstrate that E
      cadherin expression increases during nerve regeneration, and the expression was
      observed mainly in Schwann's cells. The degree of E-cadherin expression may
      affect the rate of nerve regeneration.

PMID- 11506328
TI  - Microvascular free on-top plasty in a mutilated hand.
AB  - Amputation of the index, middle, and ring fingers leaves a poor, unstable pinch
      and grasp between the thumb and little finger. In this type of mutilated hand, it
      is necessary to reconstruct one or two fingers for firm chuck pinch and good
      grasp. Functionally and cosmetically, toe transfer is superior to other methods
      of finger reconstruction because of its mobility, sensibility, pulp size, and
      nail availability. However, a transfer from the foot may not always be available.
      In such a case, any finger stump may be considered as a possible donor finger.
      The authors performed a microvascular free transfer of the remaining portion of
      the ring finger including the metacarpophalangeal joint to the top of the
      remaining portion of the index finger in a mutilated hand with intact thumb and
      little finger because the patient declined toe transfer. Postoperatively, more
      effective strength and stability, provided by three converging digits, was
      achieved in the hand. Accordingly, it was easier for the patient to grip small
      and large objects. The authors describe this procedure as a microvascular free on
      top plasty.

PMID- 11506329
TI  - Nipple piercing may be contraindicated in male patients with chest implants.
AB  - The authors present a man who underwent chest augmentation and nipple piercing.
      The patient developed chronic nipple infection, which led to unnecessary invasive
      diagnostic procedures, serious implant infection, and eventually urgent
      explantation. This unfavorable scenario illustrates the distinct features of the
      procedure in men, which includes close proximity of the nipple to the implant and
      reduced awareness by health care providers. Based on this case the authors
      recommend avoiding nipple piercing in men with chest implants.

PMID- 11506330
TI  - Superiorly based rectus abdominis wraparound flap for axillofemoral graft sepsis.
AB  - Prosthetic vascular graft sepsis, although uncommon, can lead to catastrophic
      sequelae for life and limb. Axillofemoral grafts are predisposed to sepsis and
      perigraft seromas because of their length, subcutaneous tunneling, and
      infrainguinal anastomosis, and are often performed in elderly, debilitated
      patients. The authors detail the use of a superiorly based rectus abdominis
      muscle flap, in combination with a sartorius muscle flap to salvage a
      Szilagy/Samson grade III septic axillounifemoral graft. The superiorly based
      rectus abdominis wraparound muscle flap should be considered a salvage option for
      select cases of sepsis involving axillofemoral grafts.

PMID- 11506331
TI  - Digital constriction bands in pseudoainhum: morphological radiographic, and
      histological analysis.
AB  - Pseudoainhum is a rare condition of unknown etiology that produces digital
      constricting rings, most commonly on the small fingers. A thorough discussion of
      pseudoainhum in the plastic surgical literature is apparently lacking at this
      time. The authors describe the gross morphology, radiographic and laboratory
      features, and surgical pathology of the disease, and provide well-defined
      guidelines for its treatment.

PMID- 11506332
TI  - Multiple congenital epulis of the alveolar ridge and tongue.
AB  - Congenital granular cell tumor, also known as congenital epulis, is a very rare
      lesion seen in newborns. The typical presentation is a solitary nodule occurring
      on the gingiva of the anterior alveolar ridge of either jaw. Multiple-site
      involvement is seen very seldom but has been noted on the same or different
      alveolar ridges. However, tongue involvement is exceptional, and there have been
      only three cases reported involving both the alveolus and the tongue. A female
      newborn with multiple congenital epulis on the mandibular alveolar ridge and
      tongue is presented, and her preferred treatment and histopathological diagnosis
      are discussed.

PMID- 11506333
TI  - Facial palsy and achondroplasia: a rare association.
AB  - The association of facial palsy and achondroplasia is rare. The authors present
      two cases of such association. To their knowledge this has never been described
      before in the medical literature. Both patients underwent a two-stage facial
      reanimation procedure using nerve grafting and a free gracilis muscle transfer
      with very satisfactory functional and cosmetic results.

PMID- 11506334
TI  - Sentinel node biopsy for the detection of head and neck melanoma: a review.
AB  - Worldwide incidence of malignant melanoma is on the rise. Early detection of this
      malignancy is key to survival, and in the case of more advanced malignancy, early
      and effective detection of micrometastatic disease is crucial for staging and
      therapy. Because melanoma spreads primarily via lymphatic drainage patterns,
      effective methods for tracing these pathways are of paramount importance. The
      authors summarize the efficacy of blue dye, gamma probe, and lymphoscintigraphy
      detection methods, both individually and combined; the "missed disease" (or false
      negative) rate; and the clinical discordance between expected and actual location
      of metastatic disease in head and neck melanoma. A clinical meta-analysis of
      current studies in head and neck melanoma was used to evaluate clinical data. A
      success rate of 95% to 100% for detection of sentinel lymph nodes can be achieved
      when blue dye, gamma probe, and lymphoscintigraphy techniques are combined. This
      is associated with a false-negative rate of 7.7% to 10.4%. With respect to
      intermediate-depth melanomas of the head and neck, a significant discordance
      exists between expected and actual lymphatic drainage patterns. This problem is
      best addressed using a combination of lymphoscintigraphy, blue dye, and gamma
      probe localization, which yields a success rate of 95% to 100% for detection of
      sentinel lymph nodes and a low false-negative rate of 7.7% to 10.4%. In the
      instance of a failed study, one in which sentinel nodes are not detected by the
      aforementioned methods, elective node dissection is the treatment modality of
      choice.

PMID- 11506335
TI  - The coin of the realm.

PMID- 11506336
TI  - Medial pedicled orbicularis oculi flap for medial canthal resurfacing.

PMID- 11506337
TI  - Aplasia cutis congenita of the scalp: excessive bleeding and reconstructive
      problems.

PMID- 11506338
TI  - Enchondromatosis of the hand: severe and mild forms, and treatment modalities.

PMID- 11506339
TI  - Extended latissimus dorsi musculocutaneous flap for closure of a meningomyelocele
      in a 5-hour-old neonate.

PMID- 11506340
TI  - Nasal bone destruction by a cavernous hemangioma in an elderly patient.

PMID- 11506341
TI  - Investigation of skin graft viability with DMEM and Ham's F-12 fluids.

PMID- 11506342
TI  - R. v. David Copeland (The Case of the Brixton, Brick Lane and Soho Bomber).

PMID- 11506343
TI  - Lies, damned lies, and DNA statistics: DNA match testing Bayes' Theorem, and the
      criminal courts.
AB  - This study explains the correct method for the interpretation of DNA matches by
      using Bayesian Probability, and its various traps: the DNA fallacies. The current
      approach of the Court of Appeal to the use and presentation of DNA evidence is
      outlined. A new Bayesian Fallacy is explored. Specific focus is on Norman Fenton
      and Martin Neil's recent research (Fenton and Neil, 2000) which suggests a new
      dimension in the presentation of DNA evidence in court.

PMID- 11506344
TI  - Genital injury: is it significant? A review of the literature.
AB  - The purpose of this review was to critically evaluate the available literature on
      genital injury in order to facilitate an understanding of its significance in
      relation to sexual offence trials. Wide variation exists in research objectives,
      study populations and methodology, hindering interpretation considerably. The
      most valuable research in this field identifies the range of normal genital
      findings and those associated with consensual sexual intercourse, to enable
      interpretation of genital findings in sexual assault victims. However, there are,
      unfortunately, few studies of this nature. Difficulties arise when examining
      doctors are not experienced in the genital examination of those other than sexual
      assault victims, limiting their ability to draw conclusions about genital injury
      if it is detected. If the methods of genital examination employed are not the
      same as those used to examine a wide range of non-sexual assault victims,
      comparison and thus valuable interpretation is further limited. This review of
      the literature finds that the most appropriate genital examinations and indeed
      the most legally valuable as far as interpretation is concerned, are done
      macroscopically by doctors with considerable experience in the examination of
      normal, diseased and traumatized genitalia, and a sound knowledge of the
      principles of injury interpretation. A deficiency exists in the literature in
      relation to macroscopic genital examination findings in consensually sexually
      active women who have been examined by forensically trained doctors. This
      deficiency must be addressed before the medicolegal significance of genital
      injury relating to sexual assault can be accurately interpreted, and before any
      decision is made to incorporate colposcopy or staining techniques into the
      routine assessment of sexual assault victims.

PMID- 11506345
TI  - The sexual history provisions in the Youth Justice and Criminal Evidence Act 1999
      -a violation of the right to a fair trial?
AB  - In response to the Home Office recommendations contained in Speaking Up for
      Justice (1998) the Youth Justice and Criminal Evidence Act (YJCEA) 1999
      introduced a new regime for the conduct of sexual offence trials. Section 41 of
      the Act, which came into force on 4 December 2000, brings about dramatic changes
      to the rules on the admissibility of evidence of complainants' sexual behaviour,
      severely restricting the discretion of trial judges to introduce such evidence or
      to allow questioning concerning it. This represents a radical new departure that
      will fundamentally affect an accused's position at trial. Responses to section 41
      have predictably been divided given the extremely sensitive nature of this area
      of the law of evidence and the complex set of social and political issues which
      are at stake. Many have greeted it as a long overdue reform of a system premised
      upon outmoded and sexist beliefs concerning women's sexual behaviour which has
      routinely functioned to admit prejudicial and irrelevant evidence. Others,
      predominantly within the legal profession, have expressed serious concerns over
      whether the new law is workable and the extent to which, by potentially excluding
      critically relevant evidence, it may infringe upon a defendant's right to a fair
      trial. The quality of the legislation is soon to be tested. On 26 and 27 March
      2001 the House of Lords heard an interlocutory appeal in the case of R v. A and
      were asked to decide if the new provisions, by excluding previous sexual history
      evidence between the complainant and the defendant, contravened Article 6 of the
      European Convention of Human Rights. Their Lordships are, at the time of writing,
      yet to give judgment and the fate of the defendant in question, and several
      others whose trials have been postponed pending their decision, hangs in the
      balance. This article seeks to show that the new Act, despite being well
      intentioned, does not adopt a coherent or sustainable approach to the relevance
      of previous sexual history evidence and the restrictive nature of its provisions
      are such that genuinely relevant material will be rendered inadmissible. This
      creates the risk of disembodying the case before the jury and raises the
      significant possibility that miscarriages of justice will occur. As a
      consequence, unless the legislation can be read down in such a way as to
      reintroduce a measure of judicial discretion to admit such evidence, a
      declaration of incompatibility may be called for.

PMID- 11506346
TI  - The Youth Justice and Criminal Evidence Act 1999: achieving best evidence?
AB  - The Youth Justice and Criminal Evidence Act 1999 (YJCEA) aims to help vulnerable
      and intimidated witnesses give the best evidence they can in criminal
      proceedings. This is to be achieved by allowing certain witnesses access to a
      range of special measures where it is felt that their evidence will thereby be
      improved. Reducing the stress associated with a court case will, it is hoped,
      mean that vulnerable witnesses are more confident and give better testimony. In
      addition, individuals who in the past would have been unable to participate in
      proceedings and were therefore considered incompetent to give evidence will now
      have a voice. The reasoning behind the YJCEA is clear. In cases of abuse in
      particular, the prosecution case is often based almost entirely on the evidence
      of one witness, often a child. It is important that what evidence there is in
      such situations is presented as well as possible. In the past, witnesses and
      complainants in criminal proceedings have not always been given the help they
      deserved when giving evidence. Over the years, many measures have been introduced
      to render the court process less intimidating, deriving mainly from the
      experiences of the judiciary in both criminal and family proceedings. These
      include familiarization visits, live-links and the like. The YJCEA will now bring
      many of these measures under one statutory roof. It is hoped, first, that this
      will encourage greater consistency in their application and, secondly, that
      criminal proceedings will be demystified for those that have to go through them.
      Many believe it is a step that is long overdue. Thus, vulnerable and intimidated
      witnesses, who might previously have been considered unable to give evidence in
      criminal proceedings, or at a disadvantage in giving evidence, will have a proper
      opportunity to do so. Such witnesses include the mentally and physically
      disabled, those in fear of intimidation such as the complainant of racial or
      domestic violence, and of course children. Rendering the court process less
      traumatic for those who have already been traumatized enough and maximizing the
      numbers of complainants and witnesses who can actually give evidence is
      commendable. However, the YJCEA also has its problems and as has been pointed out
      by Di Birch (2000) 'this is an Act which leaves us in no doubt where our
      sympathies lie'. The YJCEA is a complex Act that may well have a considerable
      impact on the way in which criminal proceedings in the UK are handled. I will
      consider the following areas: (i) interpretation; (ii) special measures and their
      application; and (iii) areas for concern.

PMID- 11506347
TI  - Passive euthanasia in dementia: killing ... or letting die?
AB  - A sample of carers was asked to complete a self-administered questionnaire
      designed to collect information about carers' characteristics and obtain their
      views on passive euthanasia. Each carer was given an information sheet about the
      study, which included a detailed and clear account for the different types of
      euthanasia. The study showed a strong support for passive euthanasia from the non
      professional carers of dementia patients. The strongest support was for the idea
      of a 'Living Will'. Having previous experience in looking after other people with
      dementia would appear to influence carers' perception of passive euthanasia. The
      subject of passive euthanasia and its ramifications for sufferers, carers and
      professionals warrants further exploration.

PMID- 11506348
TI  - Whither mental health legislation? (Locking up the disturbed and the deviant).
AB  - The publication of the Government's two-part White Paper - Reforming The Mental
      Health Act - provides the opportunity to review and comment upon some of its main
      proposals against a background of current concerns with issues of public
      protection in mental health and criminal justice.

PMID- 11506349
TI  - Elderly suicide and attempted suicide: one syndrome.
AB  - In this study we explore whether elderly suicide victims who had a previous
      history of attempted suicide differ from those with no similar history. A group
      of the elderly, who ended their lives with fatal self-harm (FSH) and had a
      history of deliberate self-harm (DSH) was compared to a matching group of the
      elderly who also ended their lives with FSH, but who were not known to have had
      any history of DSH. The comparison was in respect of epidemiological, social,
      psychological characteristics, service input and methods of suicide. The elderly,
      with a history of DSH, were more likely to have been known to the mental health
      services than the elderly who did not have such a history (P<.05). The two groups
      used similar methods in their final FSH act. The elderly victims of FSH with or
      without a previous history of DSH share the same characteristics. The two groups
      appear to be part of one syndrome. Deliberate self-harm in the elderly should be
      taken seriously as an unsuccessful suicide rather than a manipulative act or a
      cry for help and attention.

PMID- 11506350
TI  - The language of forensic medicine: the meaning of some terms employed.

PMID- 11506351
TI  - A review of gunshot deaths in Strathclyde--1989 to 1998.
AB  - The case files of the Department of Forensic Medicine and Science at the
      University of Glasgow were searched for deaths involving gunshot injuries for the
      years 1989 to 1998. Seventy-one such deaths were identified. These were
      overwhelmingly males (93%) with a median age of 31 (range 17-80 years).
      Information surrounding the deaths was retrieved from sudden death reports
      compiled by the Strathclyde Police and the deaths were classified as suicide,
      homicide or accident. Fifty-one of the 71 deaths (72%) were classified as
      homicide, 17 deaths (24%) as suicide with insufficient information in three
      cases. The number of deaths for each year for suicides remained relatively
      constant at between nought and three cases per year, but figures for homicides
      varied at between three and ten cases per year, with a pronounced increase in the
      last four years of the study. The median age of the suicide cases was higher (50
      years) than the homicide cases (30 years). The weapon used was predominately a
      shotgun in the suicide cases (accounting for 65%), but in homicide rifled weapons
      were the preferred weapons (59%). The site of injury was predominately the head
      in suicides, with a wider distribution in homicides, 32 per cent involving the
      head and 33 per cent also involving the chest. Alcohol intoxication was
      associated with a greater number of homicides than suicides. Homicides were noted
      to occur most frequently during the evening and early hours of the morning. The
      majority of suicides occurred at the victim's home address, while 72 per cent of
      homicides took place in the city of Glasgow.

PMID- 11506352
TI  - Road-traffic accidents--a demographic and topographic analysis.
AB  - Injuries and fatalities occur in all forms of transportation, but numerically,
      road-traffic accidents account for the great majority worldwide. There is little
      that the autopsy surgeon can contribute to the elucidation of factors leading to
      the accident as it is largely the circumstantial and forensic laboratory evidence
      which is likely to reveal a non-accidental cause. However, the doctor's role in
      detecting the compatibility/incompatibility of the injuries with those usually
      sustained in traffic accidents (to detect any which are 'atypical', e.g. focal
      depressed fracture of the skull), distinguishing antemortem from postmortem
      injuries, demonstrating the presence of any disease capable of creating sudden
      incapacity and analysing samples for alcohol/drugs, etc., can go a long way in
      assigning roles to the human and to some extent vehicular and environmental
      factors. This warrants that a meticulous autopsy be conducted and not merely a
      catalogue of injuries. It must be appreciated that a fatal accident is likely to
      result in litigation and the extent of litigation cannot be anticipated at the
      time of the autopsy. One must, therefore, aim at the close study of any accident
      victim and a careful assessment of the case is always rewarding. The present
      study was undertaken in the Department of Forensic Medicine at (a) Government
      Medical College, Jammu (1991-93), (b) Mulana Azad Medical College, New Delhi
      (1993-95) and (c) Government Medical College, Chandigarh (1994-June 2000), with
      the object of doing a comparative analysis of the various aspects of the road
      traffic accidents and accidental deaths in three topographically and
      demographically different cities in India and to suggest remedial measures to
      bring down the accident rate.

PMID- 11506354
TI  - Developmentally regulated expression of a cyclic nucleotide-gated ion channel
      from Arabidopsis indicates its involvement in programmed cell death.
AB  - Cyclic nucleotide-gated ion channels have been identified in animals and plants.
      However, the physiological role of these ion channels in plant cells and in non
      receptor cells of animals is still unknown. Here, we focused on one member of the
      large gene family of cyclic nucleotide-gated ion channels from Arabidopsis
      thaliana (L.) Heynh., AtCNGC2. The analysis of the transcriptional regulation
      revealed that expression of AtCNGC2 is low in etiolated seedlings but increases
      substantially during de etiolation. The use of promoter::GUS plants revealed that
      expression of AtCNGC2 in seedlings is highest in cotyledons after release of the
      developmental arrest by light. Expression of AtCNGC2 was also observed in later
      stages of plant development. Investigations using the promoter::GUS plants
      demonstrated that AtCNGC2 is expressed in flowers during organ senescence and in
      the dehiscence zone of siliques. Furthermore, expression of AtCNGC2 was
      transiently induced during leaf and cell culture senescence. These results
      indicate a potential function for AtCNGC2 in the initiation of developmentally
      regulated cell death programs.

PMID- 11506355
TI  - Immunohistochemical localisation of ubiquitin and the proteasome in sunflower
      (Helianthus annuus cv. Giganteus).
AB  - This study provides an immunohistochemical demonstration of the involvement of
      the ubiquitin- and proteasome-dependent pathway during differentiation and
      organogenesis in plants. The localisation of ubiquitin and the proteasome was
      studied in meristems, leaves, stems and roots of sunflower (Helianthus annuus L.
      cv. Giganteus). By using a new technique that enhances very low antigen signals,
      we obtained information on the structural distribution of the ubiquitin- and
      proteasome-dependent pathway, and of the importance of this pathway during
      organogenesis and plant development. Ubiquitin and the proteasome showed overall
      similarities in their cellular localisation. The highest antigenic signal was
      observed in the root and shoot apical meristems, in leaf primordia and vascular
      tissue. The cambium showed less expression than the apical meristems. During
      adventitious root formation in cuttings, no sign of increased expression was
      observed within dedifferentiating tissue, but as organogenesis progressed, the
      antigenic signal of ubiquitin and the proteasome gradually increased in the
      developing roots. Comparison of immunochemical results and Western blots
      demonstrated that important changes in the cellular antigen signal could only be
      detected by immunochemistry.

PMID- 11506356
TI  - Long-distance signaling within Coleus x hybridus leaves; mediated by changes in
      intra-leaf CO2?
AB  - Rapid long-distance signaling in plants can occur via several mechanisms,
      including symplastic electric coupling and pressure waves. We show here in
      variegated Coleus leaves a rapid propagation of electrical signals that appears
      to be caused by changes in intra-leaf CO2 concentrations. Green leaf cells, when
      illuminated, undergo a rapid depolarization of their membrane potential (Vm) and
      an increase in their apoplastic pH (pHa) by a process that requires
      photosynthesis. This is followed by a slower hyperpolarization of Vm and
      apoplastic acidification, which do not require photosynthesis. White (chlorophyll
      lacking) leaf cells, when in isolated white leaf segments, show only the slow
      response, but when in mixed (i.e. green and white) segments, the rapid Vm
      depolarization and increase in pHa propagate over more than 10 mm from the green
      to the white cells. Similarly, these responses propagate 12-20 mm from
      illuminated to unilluminated green cells. The fact that the propagation of these
      responses is eliminated when the leaf air spaces are infiltrated with solution
      indicates that the signal moves in the apoplast rather than the symplast. A
      depolarization of the mesophyll cells is induced in the dark by a decrease in
      apoplastic CO2 but not by an increase in pHa. These results support the
      hypothesis that the propagating signal for the depolarization of the white
      mesophyll cells is a photosynthetically induced decrease in the CO2 level of the
      air spaces throughout the leaf.

PMID- 11506357
TI  - The nucellus degenerates by a process of programmed cell death during the early
      stages of wheat grain development.
AB  - The nucellus, which is the maternal tissue of the wheat grain, degenerates during
      the early stages of development. We have investigated whether or not this
      degenerative process may be considered as programmed cell death (PCD). The
      analysis of DNA of tissues dissected from developing wheat (Triticum aestivum L.
      cv Chinese Spring) grains at 5-20 days post anthesis (dpa) showed the presence of
      DNA laddering, which is indicative of internucleosomal fragmentation of nuclear
      DNA, in maternal tissues but not in the endosperm. The TUNEL assay showed in-situ
      internucleosomal fragmentation of DNA in nuclei of parenchymal and epidermal
      cells of the nucellus, as well as in the pericarp, during the early stages of
      grain development (5 dpa). Furthermore, internucleosomal fragmentation of nuclear
      DNA was observed in nucellar projection cells in the middle stages of grain
      development (13-18 dpa), thus showing a process of PCD in these maternal tissues.
      Electron-transmission microscopy analysis allowed the morphology of PCD to be
      characterized in this plant tissue. Initially, fragmentation of the cytoplasm was
      observed, the nuclear envelope appeared dilated and to be forming vacuoles, and
      the content of heterochromatin increased. A progressive degradation of the
      cytosolic contents and organelles was observed, and the plasma membrane was
      disrupted. However, the Golgi apparatus remained intact and apparently functional
      even in the final stages of cell death.

PMID- 11506358
TI  - Expression of an abscisic acid-binding single-chain antibody influences the
      subcellular distribution of abscisic acid and leads to developmental changes in
      transgenic potato plants.
AB  - Potato (Solanum tuberosum L. cv. Desiree) plants were transformed to express a
      single-chain variable-fragment antibody against abscisic acid (ABA), and present
      in the endoplasmic reticulum at to up to 0.24% of the soluble leaf protein. The
      resulting transgenic plants were only able to grow normally at 95% humidity and
      moderate light. Four-week-old plants accumulated ABA to high extent, were
      retarded in growth and their leaves were smaller than those of control plants.
      Leaf stomatal conductivity was increased due to larger stomates. The subcellular
      concentrations of ABA in the chloroplast, cytoplasm and vacuole, and the
      apoplastic space of leaves were determined. In the 4-week-old transgenic plants
      the concentration of ABA not bound to the antibody was identical to that of
      control plants and the stomates were able to close in response to lower humidity
      of the atmosphere. A detailed analysis of age-dependent changes in plant
      metabolism showed that leaves of young transformed plants developed in ABA
      deficiency and leaves of older plants in ABA excess. Phenotypic changes developed
      in ABA deficiency partly disappeared in older plants.

PMID- 11506359
TI  - Glucocorticoid-inducible gene expression in rice.
AB  - We have studied the use of a glucocorticoid receptor-based inducible gene
      expression system in the monocotyledonous model plant rice (Oryza sativa L.).
      This system, originally developed by T. Aoyama and N.-H. Chua [(1997) Plant J 11:
      605-612], is based on the chimaeric transcriptional activator GVG, consisting of
      the yeast Gal4 DNA-binding domain, the VP16 activation domain and the
      glucocorticoid receptor domain. For application in rice, we designed an optimized
      binary vector series (pINDEX) and tested this with the beta-glucuronidase (gusA)
      reporter gene. GUS expression was tightly controlled and relatively low
      concentrations (1-10 microM) of the glucocorticoid hormone dexamethasone (DEX)
      were able to induce GUS activities to levels comparable to those conferred by the
      strong cauliflower mosaic virus (CaMV) 35S promoter. DEX was taken up efficiently
      by the roots of tissue-cultured plantlets or mature plants in hydroponic culture,
      and induced GUS activity throughout the whole plant. DEX-induced GUS expression
      patterns were consistent in all lines and their T1 progeny. The phenotype of
      tissue-cultured rice plantlets was not affected when inductions with 10-100
      microM DEX were limited to 1-4 days or when 2-week inductions were performed with
      1 microM DEX, which was already sufficient to reach near-maximal GUS activity.
      However, 2-week inductions with 10 microM DEX caused growth retardation and
      developmental defects. As the severity of these effects varied between different
      lines, we could select lines with a mild phenotype for future use as activator
      lines in crosses with 'target' plants.

PMID- 11506360
TI  - Partial purification and biochemical characterization of a heteromeric protein
      phosphatase 2A holoenzyme from maize (Zea mays L.) leaves that dephosphorylates
      C4 phosophoenolpyruvate carboxylase.
AB  - The activity and allosteric properties of plant phosphoenolpyruvate carboxylase
      (PEPC; EC 4.1.1.31) are controlled posttranslationally by specific reversible
      phosphorylation of a strictly conserved serine residue near the N-terminus. This
      up/down-regulation of PEPC is catalyzed by a dedicated and highly regulated
      serine/threonine (Ser/Thr) kinase (PEPC-kinase) and an opposing type-2A Ser/Thr
      phosphatase (PP2A). In marked contrast to PEPC-kinase, the PP2A holoenzyme from
      photosynthetic tissue has been virtually unstudied to date. In the present
      investigation, we have partially purified and characterized the native form of
      this PP2A from illuminated leaves of maize (Zea mays L.), a C4 plant, using maize
      [32P]PEPC as substrate. Various conventional chromatographic matrices, together
      with thiophosphorylated C4 PEPC-peptide and microcystin-LR affinity-supports,
      were exploited for the enrichment of this PP2A from soluble leaf extracts.
      Biochemical and immunological results indicate that the C4-leaf holoenzyme is
      analogous to other eukaryotic PP2As in being a approximately 170-kDa heteromer
      comprised of a core PP2Ac-A heterodimer (approximately 38- and approximately 65
      kDa subunits, respectively) complexed with a putative, approximately 74-kDa B
      type regulatory/targeting subunit. This heterotrimer lacks any strict substrate
      specificity in that it dephosphorylates C4 PEPC, mammalian phosphorylase a, and
      casein in vitro. This activity is independent of free Me2+, insensitive to
      levamisole and the Inhibitor-2 protein that targets PP1, activated by several
      polycations such as protamine and poly-L-lysine, and highly sensitive to
      inhibition by microcystin-LR and okadaic acid (IC50 approximately 30 pM), all of
      which are diagnostic features of yeast and mammalian PP2As. In addition, this C4
      leaf PP2A holoenzyme (i) is inhibited in vitro by physiological concentrations of
      certain C4 PEPC-related metabolites (L-malate, PEP, glucose 6-phosphate, but not
      the activator glycine) when either 32P-labeled maize PEPC or rabbit muscle
      phosphorylase a is used as substrate, suggesting a direct effect on this Ser/Thr
      phosphatase; and (ii) displays, at best, only modest light/dark effects in vivo
      on its apparent molecular mass, component core subunits and activity against C4
      PEPC, in marked contrast to the opposing activity of PEPC-kinase in C4 and
      Crassulacean acid metabolism leaves. This report represents one of the few
      studies of a heteromeric PP2A holoenzyme from photosynthetic tissue that
      dephosphorylates a known target enzyme in plants, such as PEPC, sucrose-phosphate
      synthase or nitrate reductase.

PMID- 11506361
TI  - Fluorescently-labeled fimbrin decorates a dynamic actin filament network in live
      plant cells.
AB  - Recently it has been established, through a detailed biochemical analysis, that
      recombinant Arabidopsis thaliana fimbrin 1 (AtFim1) is a member of the
      fimbrin/plastin family of actin filament bundling or cross-linking proteins [D.R.
      Kovar et al. (2000) Plant J 24:625-636]. To determine whether AtFim1 can function
      as an F-actin-binding protein in the complex environment of the plant cell
      cytoplasm, we created a fluorescent protein analog and introduced it by
      microinjection into live Tradescantia virginiana L. stamen hair cells. AtFim1
      derivatized with Oregon Green 488 had biochemical properties similar to unlabeled
      fimbrin, including the Kd value for binding to plant F-actin and the ability to
      cross-link filaments into higher-order structures. Fluorescent-fimbrin decorated
      an array of fine actin filaments in the cortical cytoplasm of stamen hair cells,
      which were shown with time-course studies to be highly dynamic. These data
      establish AtFim1 as a bona fide member of the fimbrin/plastin family, and
      represent the first use of a plant actin-binding protein as a powerful
      cytological tool for tracking the spatial and temporal redistribution of actin
      filaments in individual cells.

PMID- 11506362
TI  - The chloroplastic glutamine synthetase (GS-2) of tobacco is phosphorylated and
      associated with 14-3-3 proteins inside the chloroplast.
AB  - The chloroplastic isoform of glutamine synthetase (GS-2, EC 6.3.1.2) from
      Nicotiana tabacum L. is phosphorylated at the serine residues. At least three of
      the six GS-2 subunits separated by two-dimensional polyacrylamide gel
      electrophoresis cross-reacted with an antibody raised against phosphoserine. This
      provoked the question as to whether 14-3-3 proteins might be present in the
      chloroplast and bind to chloroplastic GS-2. Although two different 14-3-3
      proteins of 32 and 30 kDa were present in total leaf extracts, in the soluble
      fraction of chloroplasts, only the 32-kDa 14-3-3 protein was immunodetected with
      an antibody raised against a conserved region of 14-3-3 protein from corn. This
      demonstrates the presence of a chloroplast-located isoform of 14-3-3 proteins in
      tobacco. To examine a putative binding of GS-2 to these 14-3-3 proteins in vivo,
      the native GS-2 holoenzyme was probed with a 14-3-3 antibody. The strong cross
      reaction between GS-2 and the 14-3-3 antibody clearly points to a binding of GS-2
      and 14-3-3 in tobacco chloroplasts. Only those oligomers of GS-2 that were
      strongly associated with 14-3-3 proteins were catalytically active.

PMID- 11506363
TI  - Cloning, characterization and mRNA expression analysis of PVAS1, a type I
      asparagine synthetase gene from Phaseolus vulgaris.
AB  - A gene encoding a putative asparagine synthetase (AS; EC 6.3.5.4) has been
      isolated from common bean (Phaseolus vulgaris L.). A 2-kb cDNA clone of this gene
      (PVAS1) encodes a protein of 579 amino acids with a predicted molecular mass of
      65,265 Da, an isoelectric point of 6.3, and a net charge of -9.3 at pH 7.0. The
      PVAS1 protein sequence conserves all the amino acid residues that are essential
      for glutamine-dependent AS, and PVAS1 complemented an Escherichia coli asparagine
      auxotroph, which demonstrates that it encodes a glutamine-dependent AS. The PVAS1
      protein showed the highest similarity to soybean SAS1, and piled up with other
      legume ASs to form an independent dendritic group of type-I AS enzymes. Northern
      blot analyses revealed that the expression pattern of PVAS1 resembles that of
      PVAS2, another AS previously described in the common bean. Unlike PVAS2, however,
      PVAS1 was not expressed in the nodule and was not repressed by light, suggesting
      different functions for these two AS genes.

PMID- 11506364
TI  - Phenol oxidative coupling in the biogenesis of the macrocyclic spermine alkaloids
      aphelandrine and orantine in Aphelandra sp.
AB  - A crucial step in the biosynthesis of the spermine alkaloid aphelandrine and its
      diastereoisomer orantine is an intramolecular cyclization of the intermediate (S)
      dihydroxyverbacine. In order to elucidate this step of the biosynthetic pathway,
      microsomes from the roots of Aphelandra squarrosa Nees were incubated with
      unlabeled and (D8)-labeled (S)-dihydroxyverbacine. It was shown that the
      microsomal fraction catalyzes the intramolecular coupling of (S)
      dihydroxyverbacine to aphelandrine. This was proven by microsomal transformation
      of (D8)-labeled (S)-dihydroxyverbacine to (D8)-labeled aphelandrine. The reaction
      absolutely requires NAPDH and O2. The underlying reaction mechanism is probably
      an oxidative phenol coupling catalyzed by an aphelandrine synthase. This enzyme
      is proposed to be a cytochrome P-450 oxidase. The intramolecular cyclization of
      (S)-dihydroxyverbacine represents an important point in the biogenesis of the
      aphelandrine-type alkaloids.

PMID- 11506365
TI  - The contribution of plastidial phosphoglucomutase to the control of starch
      synthesis within the potato tuber.
AB  - The aim of this work was to evaluate the extent to which plastidial
      phosphoglucomutase (PGM) activity controls starch synthesis within potato
      (Solanum tuberosum L. cv. Desiree) tubers. The reduction in the activity of
      plastidial PGM led to both a correlative reduction in starch accumulation and an
      increased sucrose accumulation. The control coefficient of plastidial PGM on the
      accumulation of starch was estimated to approximate 0.24. The fluxes of
      carbohydrate metabolism were measured by investigating the metabolism of [U
      14C]glucose in tuber discs from wild-type and transgenic plants. In tuber discs
      the control coefficient of plastidial PGM over starch synthesis was estimated as
      0.36, indicating that this enzyme exerts considerable control over starch
      synthesis within the potato tuber.

PMID- 11506366
TI  - Movement and regeneration of epicuticular waxes through plant cuticles.
AB  - Regeneration of plant epicuticular waxes was studied in 24 plant species by high
      resolution scanning electron microscopy. According to their regeneration
      behaviour, four groups could be distinguished: (i) regeneration occurs at all
      stages of development; (ii) regeneration occurs only during leaf expansion; (iii)
      regeneration occurs only in fully developed leaves; (iv) plants were not able to
      regenerate wax. Wax was removed from the leaves with water-based glue and a
      liquid polymer, i.e. water-based polyurethane dispersion. In young leaves these
      coverings could not be removed without damaging the leaves. After a few days,
      waxes appeared on the surface of these polymer films, which still adhered to the
      leaves. It is concluded that waxes move through the cuticle in a process similar
      to steam distillation. This hypothesis could be further substantiated in refined
      in vitro experiments. Wax isolated from Eucalyptus globulus was applied to a
      filter paper, subsequently covered with a liquid polymer and fixed onto a
      diffusion chamber filled with water. The diffusion chamber was put into a
      desiccator. After 8-10 days at room temperature, crystals similar in dimensions
      and shape to in situ crystals appeared on the surface of the polyurethane film.
      This indicates that waxes in molecular dimensions move together with the water
      vapor that permeates through the polymer membrane. Based on these results, we
      propose a new and simple hypothesis for the mechanism of wax movement: the
      molecules that finally form the epicuticular wax crystals are moved in the
      cuticular water current.

PMID- 11506367
TI  - Solubilization of rhamnogalacturonan I galactosyltransfrases from membranes of a
      flax cell suspension.
AB  - Galactosyltransferases (GalTs), capable of transferring a galactosyl residue from
      UDP-galactose (UDP-Gal) to polysaccharide acceptor, were solubilized from flax
      (Linum usitatissimum L.) membranes using 0.5% CHAPS. The observed requirement for
      a rhamnogalacturonan I (RG-I) exogenous substrate to stimulate the solubilized
      GalT activity provided the first evidence for the presence of RG-I GalT
      activities in flax cells. An assay to measure specifically the products of this
      RG-I GalT activity was designed, based on size-exclusion chromatography. Labelled
      products were characterized as an RG-I polymer by using purified RG-I hydrolase
      or lyase. At pH 8 and in the presence of 5 mM CaCl2, beta-D-galactosyl residues
      were specifically transferred onto RG-I branches of short beta-(1 --> 4)-D
      galactan side chains. These side chains were liable to hydrolysis by beta
      galactosidase and endo-beta-(1 --> 4)-D-galactanase. The RG-I GalT had a
      temperature optimum of 30 degrees C. an apparent Km for UDP-Gal and exogenous RG
      I substrate of 460 +/- 40 microM and 1.1 +/- 0.1 mg ml(-1) respectively, and a
      Vmax of 3.0 +/- 0.5 pkat mg(-1) protein.

PMID- 11506368
TI  - The de-epoxidase and epoxidase reactions of Mantoniella squamata (Prasinophyceae)
      exhibit different substrate-specific reaction kinetics compared to spinach.
AB  - In vivo the prasinophyceaen alga Mantoniella squamata Manton et Parke uses an
      incomplete violaxanthin (Vx) cycle, leading to a strong accumulation of
      antheraxanthin (Ax) under conditions of high light. Here, we show that this
      zeaxanthin (Zx)-depleted Vx/Ax cycle is caused by an extremely slow second de
      epoxidation step from Ax to Zx, and a fast epoxidation from Ax back to Vx in the
      light. The rate constant of Ax epoxidation is 5 to 6 times higher than the rate
      constant of Zx formation, implying that Ax is efficiently converted back to Vx
      before it can be de-epoxidated to Zx. It is, however, only half the rate constant
      of the first de-epoxidation step from Vx to Ax, thus explaining the observed net
      accumulation of Ax during periods of strong illumination. When comparing the rate
      constant of the second de-epoxidation step in M. squamata with Zx formation in
      spinach (Spinacia oleracea L.) thylakoids, we find a 20-fold reduction in the
      reaction kinetics of the former. This extremely slow Ax de-epoxidation, which is
      also exhibited by the isolated Mantoniella violaxanthin de-epoxidase (VDE), is
      due to a reduced substrate affinity of M. squamata VDE for Ax compared with the
      VDE of higher plants. Mantoniella VDE, which has a similar Km value for Vx, shows
      a substantially increased Km for the substrate Ax in comparison with spinach VDE.
      Our results furthermore explain why Zx formation in Mantoniella cells can only be
      found at low pH values that represent the pH optimum of VDE. A pH of 5 blocks the
      epoxidation reaction and, consequently, leads to a slow but appreciable
      accumulation of Zx.

PMID- 11506369
TI  - Effects of cytoplasmic Mg2+ on slowly activating channels in isolated vacuoles of
      Beta vulgaris.
AB  - The slow vacuolar (SV) channel can mediate a large part of the ionic current in
      plant tonoplasts, but its actual physiological role is still unclear. We
      demonstrate that in vacuoles from the taproots of sugar beet (Beta vulgaris L.),
      besides Ca2+, cytoplasmic Mg2+ also plays an important role in promoting the
      activation of the SV channel. An increase in Mg2+ concentration decreases the
      time constants of channel activation and deactivation, and determines a
      consistent shift, towards negative voltages, of the conductance characteristic;
      as an example, when the free concentration of Mg2+ was increased from the
      micromolar range up to 10 mM the activation shifted by about -60 mV. The
      experimental results obtained, which are based on a fast perfusion procedure
      allowing us to change the solution bathing the vacuole in a few milliseconds,
      suggest that magnesium-binding is a faster process than the voltage-activation
      gating of the channel, which constitutes the rate-limiting step controlling
      channel opening. Interestingly, the activation of the channel mediated by Mg2+
      depends on the cooperative binding of at least three magnesium ions. We verified
      that cytoplasmic magnesium favours the activation of SV channels in the presence
      of nanomolar cytoplasmic calcium concentrations. A critical discussion on the
      Calcium Induced Calcium Release (CICR) mechanism proposed for the SV channel is
      presented.

PMID- 11506370
TI  - Identification of a transcription factor specifically expressed at the onset of
      leaf senescence.
AB  - The differential expression of genes was analyzed during leaf senescence in
      Arabidopsis thaliana (L.) Heynh., using suppression subtractive hybridization
      (SSH). In order to characterize the differential expression of regulatory genes,
      the analysis was performed at a very early time point when leaves first differed
      in their photochemical efficiency (Fv/Fm) and cab transcript levels, but no
      visible sign of senescence, and no expression of SAG12 could be determined. After
      high-throughput screening, we isolated several differentially expressed cDNA
      clones, including a transcription factor of the WRKY family, WRKY53. All family
      members contained the WRKY domain, a 60-amino-acid domain with the conserved
      WRKYGQK motif at the N-terminal end, together with a novel zinc-finger motif. The
      mRNA level of WRKY53 increased substantially within the rosette leaves of a 6
      week-old plant before the expression of SAG12 became detectable, was constant in
      all leaves of a 7-week-old plant and decreased again in 8-week-old plants. This
      indicates that WRKY53 is expressed at a very early time point of leaf senescence
      and might therefore play a regulatory role in the early events of leaf
      senescence.

PMID- 11506371
TI  - Radial widening of the Casparian strip follows induced radial expansion of
      endodermal cells.
AB  - The Casparian strip, the barrier to apoplastic transport that is located at the
      endodermis in roots and stems, is formed by individual endodermal cells and is
      constructed as a highly organized mesh within the primary wall. Since little is
      known about the mechanism of formation of the strip, we tried to obtain
      morphological evidence for the existence, prior to suberization and
      lignification, of some regulatory system at the expected site of the strip.
      Endodermal cells in etiolated pea stems were induced to expand in the radial
      direction by piercing the stems through the cortex before formation of the strip.
      The radial width of the strip increased significantly with the expansion of the
      radial walls of these endodermal cells. The expansion of the cells occurred
      before the formation of the strip. However, strips that had already been formed
      when the stems were pierced did not increase in width despite an induced
      expansion of the radial walls. These observations suggest that some positional
      information exists in the radial wall of endodermal cells that defines the future
      site of formation of the strip and its width.

PMID- 11506372
TI  - Starch synthesis in transgenic potato tubers with increased 3-phosphoglyceric
      acid content as a consequence of increased 6-phosphofructokinase activity.
AB  - The aim of this work was to test the hypothesis that changes in cytosolic 3
      phosphoglyceric acid (3-PGA) content can regulate the rate of starch synthesis in
      potato (Solanum tuberosum L.) tubers. The amount of 3-PGA was increased by
      expressing bacterial phosphofructokinase (PFK; EC 2.7.1.11) in transgenic potato
      tubers. The resultant 3-fold increase in PFK activity was accompanied by an
      increase in metabolites downstream of PFK, including a 3-fold increase in 3-PGA.
      There was also a decrease in metabolites upstream of PFK, most notably of glucose
      6-phosphate. The increase in 3-PGA did not affect the amount of starch that
      accumulated in developing tubers, nor its rate of synthesis in tuber discs cut
      from developing tubers. This suggests that changes in cytosolic 3-PGA may not
      affect the rate of starch synthesis under all circumstances. We propose that in
      this case, a decrease in glucose-6-phosphate (which is transported into the
      amyloplast as a substrate for starch synthesis) may be sufficient to counteract
      the effect of increased 3-PGA.

PMID- 11506373
TI  - First isolation of an isoprene synthase gene from poplar and successful
      expression of the gene in Escherichia coli.
AB  - For the first time, the complete functional gene for isoprene synthase has been
      isolated from poplar (Populus alba x Populus tremula). The gene was quite similar
      to known limonene and other monoterpene synthases, but was found to specifically
      catalyze the formation of isoprene from the precursor dimethylallyl diphosphate
      with only a marginal activity for the formation of the monoterpene limonene from
      geranyl diphosphate as compared with limonene synthases. Omitting the part of the
      gene that putatively encoded the signal peptide necessary for transport into the
      chloroplast led to an enhanced rate of isoprene formation by the recombinant
      protein.

PMID- 11506374
TI  - Short photoperiod inhibits winter growth of subtropical grasses.
AB  - Grass development is influenced by length of photoperiod, but no direct
      measurements under natural conditions exist on mass accumulation in response to
      photoperiod by subtropical grass species. Grasslands of the subtropics are a
      major resource, but their growth is inhibited substantially during the short
      photoperiod months. This research was designed to examine the consequences on
      grass production under field conditions when the limitation of short photoperiod
      is artificially removed. Lights, which extended the daylength to 15 h, were
      placed over plots of four subtropical forage grasses representing three species
      (Paspalum notatum Flugge; Cynodon dactylon L.; Cynodon nlemfuensis Vanderyst) to
      measure their mass accumulation in response to extended photoperiod in a 2-year
      experiment. Forage yields in all grasses at 5-week harvests during the time of
      shortest daylength were increased up to 6.2-fold more than the yield under the
      natural daylength. For the 4.5-month period of shortest daylength in each year,
      forage yields were increased for all grasses with one grass having a yield
      increase of 3.6-fold under the extended photoperiod as compared to natural
      daylength. These results demonstrated that selection of grasses that are
      insensitive to photoperiod could substantially increase forage yield of
      subtropical grasslands to benefit animal production and enhance carbon
      sequestration.

PMID- 11506375
TI  - Mammalian photoperiodic system: formal properties and neuroendocrine mechanisms
      of photoperiodic time measurement.
AB  - Photoperiodism is a process whereby organisms are able to use both absolute
      measures of day length and the direction of day length change as a basis for
      regulating seasonal changes in physiology and behavior. The use of day length
      cues allows organisms to essentially track time-of-year and to "anticipate"
      relatively predictable annual variations in important environmental parameters.
      Thus, adaptive types of seasonal biological changes can be molded through
      evolution to fit annual environmental cycles. Studies of the formal properties of
      photoperiodic mechanisms have revealed that most organisms use circadian
      oscillators to measure day length. Two types of paradigms, designated as the
      external and internal coincidence models, have been proposed to account for
      photoperiodic time measurement by a circadian mechanism. Both models postulate
      that the timing of light exposure, rather than the total amount of light, is
      critical to the organism's perception of day length. In mammals, a circadian
      oscillator(s) in the suprachiasmatic nucleus of the hypothalamus receives photic
      stimuli via the retinohypothalamic tract. The circadian system regulates the
      rhythmic secretion of the pineal hormone, melatonin. Melatonin is secreted at
      night, and the duration of secretion varies in inverse relation to day length;
      thus, photoperiod information is "encoded" in the melatonin signal. The melatonin
      signal is presumably "decoded" in melatonin target tissues that are involved in
      the regulation of a variety of seasonal responses. Variations in photoperiodic
      response are seen not only between species but also between breeding populations
      within a species and between individuals within single breeding populations.
      Sometimes these variations appear to be the result of differences in
      responsiveness to melatonin; in other cases, variations in photoperiod
      responsiveness may depend on differences in patterns of melatonin secretion
      related to circadian variation. Sites of action for melatonin in mammals are not
      yet well characterized, but potential targets of particular interest include the
      pars tuberalis of the pituitary gland and the suprachiasmatic nuclei. Both these
      sites exhibit uptake of radiolabeled melatonin in various species, and there is
      some evidence for direct action of melatonin at these sites. However, it appears
      that there are species differences with respect to the importance and specific
      functions of various melatonin target sites.

PMID- 11506376
TI  - Encoding le quattro stagioni within the mammalian brain: photoperiodic
      orchestration through the suprachiasmatic nucleus.
AB  - Within the suprachiasmatic nucleus (SCN) is a pacemaker that not only drives
      circadian rhythmicity but also directs the circadian organization of
      photoperiodic (seasonal) timekeeping. Recent evidence using electrophysiological,
      molecular, and genetic tools now strongly supports this conclusion. Important
      questions remain regarding the SCN's precise role(s) in the brain's photoperiodic
      circuits, especially among different species, and the cellular and molecular
      mechanisms for its photoperiodic "memory." New data suggesting that SCN "clock"
      genes may also function as "calendar" genes are a first step toward understanding
      how a photoperiodic clock is built from cycling molecules.

PMID- 11506377
TI  - Of rodents and ungulates and melatonin: creating a uniform code for darkness by
      different signaling mechanisms.
AB  - Melatonin synthesis in the mammalian pineal gland is one of the best investigated
      output pathways of the circadian clock because it can be readily measured and is
      tightly regulated by a clearly defined input, the neurotransmitter
      norepinephrine. In this system, a regulatory scenario was deciphered that is
      centered around the cyclic AMP pathway but shows peculiar species-specific
      differences. In rodents, the cyclic AMP-mediated, temporally sequential up
      regulation of two transcription factors, the activator CREB (cyclic AMP
      responsive element-binding protein) and the inhibitor ICER (inducible cyclic AMP
      dependent early repressor), is the core mechanism to determine rhythmic
      accumulation of the mRNA encoding for the rate-limiting enzyme in melatonin
      synthesis, the arylalkylamine N-acetyltransferase (AA-NAT). Thus, in rodents, the
      regulation of melatonin synthesis bears an essential transcriptional component,
      which, however, is flanked by posttranscriptional mechanisms. In contrast, in
      ungulates, and possibly also in primates, AA-NAT appears to be regulated
      exclusively on the posttranscriptional level. Here, increasing cyclic AMP levels
      inhibit the breakdown of constitutively synthesized AA-NAT protein by proteasomal
      proteolysis, leading to an elevated enzyme activity. Thus, self-restriction of
      cellular responses, as a reaction to external cues, is accomplished by different
      mechanisms in pinealocytes of different mammalian species. In such a temporally
      gated cellular adaptation, transcriptionally active products of clock genes may
      play a supplementary role. Their recent detection in the endogenously oscillating
      nonmammalian pineal organ and, notably, also in the slave oscillator of the
      mammalian pineal gland underlines that the mammalian pineal gland will continue
      to serve as an excellent model system to understand mechanisms of biological
      timing.

PMID- 11506378
TI  - Decoding photoperiodic time and melatonin in mammals: what can we learn from the
      pars tuberalis?
AB  - The cellular and molecular mechanisms through which the melatonin signal is
      decoded to drive/synchronize photoperiodic responses remain unclear. Much of our
      current understanding of the processes involved in this readout derives from
      studies of melatonin action in the pars tuberalis of the anterior pituitary.
      Here, the authors review current knowledge and highlight critical gaps in our
      present understanding.

PMID- 11506379
TI  - Biology of mammalian photoperiodism and the critical role of the pineal gland and
      melatonin.
AB  - In mammals, photoperiodic information is transformed into a melatonin secretory
      rhythm in the pineal gland (high levels at night, low levels during the day).
      Melatonin exerts its effects in discrete hypothalamic areas, most likely through
      MT1 melatonin receptors. Whether melatonin is brought to the hypothalamus from
      the cerebrospinal fluid or the blood is still unclear. The final action of this
      indoleamine at the level of the central nervous system is a modulation of GnRH
      secretion but it does not act directly on GnRH neurones; rather, its action
      involves a complex neural circuit of interneurones that includes at least
      dopaminergic, serotoninergic and aminoacidergic neurones. In addition, this
      network appears to undergo morphological changes between seasons.

PMID- 11506380
TI  - Photoperiodism in humans and other primates: evidence and implications.
AB  - Most of the anatomical and molecular substrates of the system that encodes
      changes in photoperiod in the duration of melatonin secretion, and the receptor
      molecules that read this signal, have been shown to be conserved in monkeys and
      humans, and the functions of this system appear to be intact from the level of
      the retina to the level of the melatonin-duration signal of change of season.
      While photoperiodic seasonal breeding has been shown to occur in monkeys, it
      remains unclear whether photoperiod and mediation of photoperiod's effects by
      melatonin influence human reproduction. Epidemiological evidence suggests that
      inhibition of fertility by heat in men in summer contributes to seasonal
      variation in human reproduction at lower latitudes and that stimulation of
      fertility by lengthening of the photoperiod in spring contributes to the
      variation at higher latitudes. Parallels between the seasonality of human
      reproduction and seasonal affective disorder suggest that they may be governed by
      common biological processes. Historical and experimental evidence indicates that
      human responses to seasonal changes in the natural photoperiod may have been more
      robust prior to the Industrial Revolution and that subsequently they have been
      increasingly suppressed by alterations of the physical environment.

PMID- 11506381
TI  - Photoperiodic control of seasonality in birds.
AB  - This review examines how birds use the annual cycle in photoperiod to ensure that
      seasonal events--breeding, molt, and song production--happen at the appropriate
      time of year. Differences in breeding strategies between birds and mammals
      reflect basic differences in biology. Avian breeding seasons tend to be of
      shorter duration and more asymmetric with respect to changes in photoperiod.
      Breeding seasons can occur at the same time each year (predictable) or at
      different times (opportunistic), depending on the food resource. In all cases,
      there is evidence for involvement of photoperiodic control, nonphotoperiodic
      control, and endogenous circannual rhythmicity. In predictable breeders (most
      nontropical species), photoperiod is the predominant proximate factor. Increasing
      photoperiods of spring stimulate secretion of gonadotropin-releasing hormone
      (GnRH) and consequent gonadal maturation. However, breeding ends before the
      return of short photoperiods. This is the consequence of a second effect of long
      photoperiods--the induction of photorefractoriness. This dual role of long
      photoperiods is required to impart the asymmetry in breeding seasons. Typically,
      gonadal regression through photorefractoriness is associated with a massive
      decrease in hypothalamic GnRH, essentially a reversal to a pre-pubertal
      condition. Although breeding seasons are primarily determined by photoperiodic
      control of GnRH neurons, prolactin may be important in determining the exact
      timing of gonadal regression. In tropical and opportunistic breeders, endogenous
      circannual rhythmicity may be more important. In such species, the reproductive
      system remains in a state of "readiness to breed" for a large part of the year,
      with nonphotic cues acting as proximate cues to time breeding. Circannual
      rhythmicity may result from a temporal sequence of different physiological states
      rather than a molecular or cellular mechanism as in circadian rhythmicity. Avian
      homologues of mammalian clock genes Per2, Per3, Clock, bmal1, and MOP4 have been
      cloned. At the molecular level, avian circadian clocks appear to function in a
      similar manner to those of mammals. Photoperiodic time measurement involves
      interaction between a circadian rhythm of photoinducibility and, unlike mammals,
      deep brain photoreceptors. The exact location of these remains unclear. Although
      the eyes and pineal generate a daily cycle in melatonin, this photoperiodic
      signal is not used to time seasonal breeding. Instead, photoperiodic responses
      appear to involve direct interaction between photoreceptors and GnRH neurons.
      Thyroid hormones are required in some way for this system to function. In
      addition to gonadal function, song production is also affected by photoperiod.
      Several of the nuclei involved in the song system show seasonal changes in
      volume, greater in spring than in the fall. The increase in volume is, in part,
      due to an increase in cell number as a result of neurogenesis. There is no
      seasonal change in the birth of neurons but rather in their survival.
      Testosterone and melatonin appear to work antagonistically in regulating volume.

PMID- 11506382
TI  - Insect photoperiodism and circadian clocks: models and mechanisms.
AB  - Photoperiodic clocks allow organisms to predict the coming season. In insects,
      the seasonal adaptive response mainly takes the form of diapause. The extensively
      studied photoperiodic clock in insects was primarily characterized by a "black
      box" approach, resulting in numerous cybernetic models. This is in contrast with
      the circadian clock, which has been dissected pragmatically at the molecular
      level, particularly in Drosophila. Unfortunately, Drosophila melanogaster, the
      favorite model organism for circadian studies, does not demonstrate a pronounced
      seasonal response, and consequently molecular analysis has not progressed in this
      area. In the current article, the authors explore different ways in which
      identified molecular components of the circadian pacemaker may play a role in
      photoperiodism. Future progress in understanding the Drosophila circadian
      pacemaker, particularly as further output components are identified, may provide
      a direct link between the clock and photoperiodism. In addition, with improved
      molecular tools, it is now possible to turn to other insects that have a more
      dramatic photoperiodic response.

PMID- 11506383
TI  - Regulation of seasonal reproduction in mollusks.
AB  - Understanding the physiological basis of environmental regulation of reproduction
      at the cellular level has been difficult or unfeasible in vertebrate species
      because of the highly complex and diffuse nature of vertebrate neuroendocrine
      systems. This is not the case with the simple nervous system of mollusks in which
      reproductive neuroendocrine cells are often readily identifiable in living
      tissue. Given that there are mollusks that are seasonal breeders, that the
      neuroendocrine cells controlling reproduction have been identified in several
      molluskan species, that these neurons are conducive to cell physiological
      analysis, and that basic features of cell biology have been highly conserved
      between mammals and mollusks, it seems that the mollusk would provide an
      excellent model system to investigate cell-physiological events that mediate
      effects of environmental signals on reproduction. The purpose of this review is
      to explore this idea in three species in which the topic of the neural basis of
      seasonal reproduction has been studied: the giant garden slug Limax maximus, the
      freshwater pond snail Lymnaea stagnalis, and the marine snail Aplysia
      californica.

PMID- 11506384
TI  - Seasonality and photoperiodism in fungi.
AB  - This review gives a retrospective of what is known about photoperiodism in fungi,
      which is largely based on reports about seasonal spore concentrations. Relatively
      few species have been investigated under laboratory conditions, so that our
      knowledge whether seasonal reproduction in fungi is mainly a direct response to
      environmental conditions or whether it involves a photoperiodic machinery with
      memory capacities and a relationship to the circadian system is extremely
      limited. To form a basis for further experimental endeavors into fungal
      photoperiodism, we review the reports about endogenous rhythms and photobiology.
      Finally, we will look at the possibilities of using the fungal circadian model
      system of Neurospora crassa for future work on photoperiodism.

PMID- 11506385
TI  - Day-length perception and the photoperiodic regulation of flowering in
      Arabidopsis.
AB  - The flowering of Arabidopsis plants is accelerated by long-day photoperiods, and
      recent genetic studies have identified elements of the photoperiodic timing
      mechanism. These elements comprise genes that regulate the function of the
      circadian clock, photoreceptors, and downstream components of light signaling
      pathways. These results provide evidence for the role of the circadian clock in
      photoperiodic time measurement and suggest that photoperiod perception may follow
      Pittendrigh's external coincidence model. T-cycle experiments indicated that
      changes in the timing of circadian rhythms, relative to dawn and dusk, correlated
      with altered flowering time. Thus, the perception of photoperiod maybe mediated
      by adjustments in the phase of the circadian cycle that arise upon re-entrainment
      to a different light-dark cycle. The nature of the rhythm underlying the floral
      response is not known, but candidate molecules have been identified.

PMID- 11506386
TI  - Toward a molecular biological calendar?

PMID- 11506387
TI  - Targets of glucocorticoid action on TNF-alpha release by macrophages.
AB  - Glucocorticoid drugs affect virtually every cell type involved in inflammatory
      response, to some degree. Macrophage/monocytes (Mphi) are particularly sensitive,
      and glucocorticoids suppress release of most known Mphi inflammatory mediators,
      including TNF-alpha. In the case of TNF-alpha, several levels of regulation are
      already characterised and ongoing research hints at further glucocorticoid
      targets. The relative importance of transcriptional and post-transcriptional
      regulation is lineage-dependent and may also change during the course of Mphi
      differentiation. In human monocytic cell lines, glucocorticoids primarily
      suppress transcriptional activation through adjacent promoter binding sites for
      NF-kappaB transcription factor complexes and for complexes of c-Jun with
      activating transcription factor-2 (ATF-2). The goal of glucocorticoid research in
      inflammation is to develop drugs with the anti-inflammatory potential of
      glucocorticoids, but without the systemic toxicity. Each of the multiple targets
      for glucocorticoid action presents an opportunity for anti-inflammatory drug
      development. However, none of the known targets is unique to Mphi, and no single
      pathway is preeminent in all situations. Research is now directed at
      characterising targets and regulating them without systemic activation of the
      glucocorticoid receptor.

PMID- 11506388
TI  - H2O2 impairs inflammatory mediator release from immunologically stimulated RBL
      2H3 cells through a redox-sensitive, calcium-dependent mechanism.
AB  - OBJECTIVES: In this study we examined the effects of the inflammatory agent
      hydrogen peroxide (H2O2) on IgE-mediated mast cell responses. MATERIALS AND
      METHODS: Release of preformed granular mediators and newly synthesised TNF-alpha
      were measured in the RBL-2H3 mast cell line stimulated through IgE receptors
      (FcepsilonRI) in the presence of varying concentrations of H2O2. The sensitivity
      of the intracellular calcium response to H2O2 exposure was investigated. RESULTS:
      We found that H2O2 treatment impaired the release of preformed and newly
      synthesised mediators. H2O2 treatment simultaneously led to a profound inhibition
      of the calcium response. Calcium fluxes from both intra- and extracellular
      sources were impaired. H2O2 action was dependent on the intracellular redox
      state. Receptor activation directly stimulated intracellular H2O2 production.
      CONCLUSION: While in many cells H2O2 induces potent inflammatory responses we
      show that it can be an anti-inflammatory agent by not only inhibiting the release
      of preformed mediators but also by affecting the secretion of newly synthesized
      TNF-alpha. Inhibition is a consequence of the profound effect on intracellular
      calcium levels. The activation of an intracellular oxidative burst by FcepsilonRI
      aggregation and the sensitivity of intracellular responses to redox-altering
      agents point to an important regulatory mechanism of mast cell responses in
      inflammatory tissues.

PMID- 11506389
TI  - Immunohistopathological appearance of three different types of injury in human
      skin.
AB  - OBJECTIVE AND DESIGN: To determine whether underlying mechanisms of inflammation,
      like cellular infiltrates, expression of adhesion molecule and cytokine patterns
      are similar under different conditions of injury. Skin biopsies were taken of
      three different groups of patients in which local inflammation of the skin might
      occur. MATERIAL, PATIENTS: Skin activation was studied as a result of incision
      during surgery under aseptic conditions, as a result of a local bacterial
      infection and as a result of blunt trauma, resulting in a femoral fracture,
      without disruption of the epithelial barrier. METHODS: Skin biopsies were snap
      frozen for immunohistochemical analysis. RESULTS: Incision of the skin resulted
      in a granulocyte infiltrate, paralleled by E-selectin expression. As a result of
      infection granulocytes were observed and monocyte/macrophage and T cell numbers
      were increased. Furthermore, E-selectin, VCAM-1 and ICAM-1 expression increased
      and cytokine expression markedly changed compared to normal skin. Skin taken at
      the site of the femoral fracture showed no signs of inflammation. CONCLUSION:
      Different stimuli lead to different local inflammatory responses in human skin.

PMID- 11506390
TI  - Human umbilical cord blood monocyte-derived eosinophils produce superoxide but
      not nitric oxide.
AB  - OBJECTIVE: To investigate whether in vitro derived eosinophils release nitric
      oxide (NO), whose role in the pathogenesis of asthma is under intense debate.
      MATERIALS AND METHODS: Human umbilical cord mononuclear cells were isolated from
      umbilical cord blood cells and cultured in vitro in presence of interleukin-3 and
      interleukin-5. Superoxide generation was monitored with dihydrorhodamine-123, NO
      release was estimated by measuring the accumulation of nitrite. Expression of NO
      synthases proteins was detected by immunoblotting. RESULTS: Both N-formyl-L
      Methionyl-L-Leucyl-L-Phenylalanine, and 1-O-Alkyl-2-acetyl-sn-glyceryl-3
      phosphorylcholine induced superoxide release in umbilical cord eosinophils, while
      no response was observed with lipopolysaccharide, interleukin-4 and/or interferon
      gamma. Furthermore, upon activation with different inflammatory stimuli, neither
      induction of nitric oxide synthesis nor expression of the constitutive and/or
      inducible nitric oxide synthase were observed in these eosinophils derived in
      vitro. CONCLUSION: Human umbilical cord derived eosinophils are able to produce
      superoxide as peripheral blood eosinophils. Whether human peripheral eosinophils
      are capable of NO synthesis is still the subject of considerable debate,
      nevertheless, our results suggest that these in vitro derived eosinophils are not
      capable of nitric oxide synthesis.

PMID- 11506391
TI  - Decreased expression of P-glycoprotein in interleukin-1beta and interleukin-6
      treated rat hepatocytes.
AB  - OBJECTIVE AND DESIGN: As acute inflammation is known to cause a reduction in
      hepatic P-Glycoprotein (PGP) expression and activity in rats, we tested the
      hypothesis that the pro-inflammatory cytokines interleukin (IL-)1beta and IL-6
      also mediate reductions in PGP. METHODS: Hepatocytes were incubated with 0-50
      ng/ml of cytokine for 24-72 h. PGP/mdr expression was examined by immunodetection
      and quantitative RT-PCR analysis and PGP efflux activity was assayed. RESULTS:
      PGP protein was significantly reduced in cells treated for 3 days with IL-1beta
      and 24 h with IL-6 (p < 0.05), maximal effects occurring at 5 ng/ml for each
      cytokine. PGP activity was reduced in both IL-1beta and IL-6 treated cells (p <
      0.05). mdr1 mRNA was decreased in cells treated with IL-6, but not IL-1beta. spgp
      and mdr2 were not affected. CONCLUSIONS: Our data indicate that IL-6 and IL-1beta
      have suppressive effects on the expression and activity of PGP in cultured
      hepatocytes, likely occurring through distinct mechanisms. These cytokines may
      have a potential role in PGP regulation during inflammatory responses.

PMID- 11506392
TI  - Anti-inflammatory planar chiral [2.2]paracyclophaneacetic acid enantiomers.
AB  - OBJECTIVE AND DESIGN: To elucidate if the planar chiral paracyclophane moiety
      conveys pharmacological activity to arylacetic acid analogs in two animal models.
      MATERIAL OR SUBJECTS: Female NMRI mice (6 mice/group); female Wistar rats (8
      rats/group); thrombocytes from human blood. TREATMENT: The enantiomers of
      [2.2]paracyclophaneacetic acid were applied locally (10(-7) and 10(-6) mol/ear)
      and orally (10-100 mg/kg). METHODS: (a) Phorbol myristyl acetate model of acute
      inflammation of the inner auricle. (b) Oxazolone model of allergic contact
      dermatitis. (c) Carrageenan model of acute inflammation. (d) Inhibition of
      cyclooxygenase-1 and 12-lipoxygenase (in vitro). RESULTS: (a) PMA model: pR-(-)
      [2.2]paracyclophaneacetic acid (10(-6) mmol/ear): 58% inhibition after 24 h (p <
      0.05). (b) Oxazolone model: pR-(-)-[2.2]paracyclophaneacetic acid (10(-6)
      mmol/ear): 42% inhibition after 24 h (p < 0.05). (c) Carrageenan model: pR-(-)
      [2.2]paracyclophaneacetic acid (10 mg/kg): 31.4% inhibition (paw volume 0.48 +/-
      0.13 ml). (d) Cyclooxygenase-1 and 12-lipoxygenase: no inhibition at
      concentrations up to 10 microM. CONCLUSIONS: The easily accessible
      [2.2]paracyclophane moiety should find its use in medicinal chemistry as it is a
      pharmacophoric substituent with the interesting feature of planar chirality.

PMID- 11506393
TI  - IL-1 activates two phospholipid signaling pathways in intestinal epithelial
      cells.
AB  - OBJECTIVE AND DESIGN: the aim of the study was to decipher the molecular signals
      involved in IL-I's action on intestinal epithelial cells (IEC). MATERIALS AND
      METHODS: Mode-K cells, used as a model of IEC, were treated with IL-I, and PLA2
      activity and PGE2, ceramide, and cyclooxygenase-2 (COX-2) levels were measured
      using enzyme-immuno-assay kit, EIA, thin-layer chromatography and western
      blotting assays respectively. RESULTS: IL-I caused a concentration- and time
      dependent increase in PLA2 activity (3-fold increase), in ceramide levels (peak
      increase = 10.5 +/- 0.9 pmol/nmol phosphate), and in COX-2 and PGE2 levels. PGE2
      increase was biphasic with an early peak at 10 min (around 5 ng/mg protein) due
      to increased PLA2 activity. The later peak (13.1 +/- 1.9 ng/mg protein) at 4 h
      was due to COX-2 induction. CONCLUSION: In conclusion, these findings demonstrate
      that IL-I regulates IEC function through two pathways, the PLA2 and the
      sphingomyelin pathways, both of which are capable of modulating the inflammatory
      process.

PMID- 11506394
TI  - Aerobic conditioning in patients with mitochondrial myopathies: physiological,
      biochemical, and genetic effects.
AB  - Aerobic training has been shown to increase work and oxidative capacity in
      patients with mitochondrial myopathies, but the mechanisms underlying improvement
      are not known. We evaluated physiological (cycle exercise, 31P-MRS), biochemical
      (enzyme levels), and genetic (proportion of mutant/wild-type genomes) responses
      to 14 weeks of bicycle exercise training in 10 patients with heteroplasmic
      mitochondrial DNA (mtDNA) mutations. Training increased peak work and oxidative
      capacities (20-30%), systemic arteriovenous O2 difference (20%), and 31P-MRS
      indices of metabolic recovery (35%), consistent with enhanced muscle oxidative
      phosphorylation. Mitochondrial volume in vastus lateralis biopsies increased
      significantly (50%) and increases in deficient respiratory chain enzymes were
      found in patients with Complex I (36%) and Complex IV (25%) defects, whereas
      decreases occurred in 2 patients with Complex III defects (approximately 20%).
      These results suggest that the cellular basis of improved oxygen utilization is
      related to training-induced mitochondrial proliferation likely resulting in
      increased levels of functional, wild-type mtDNA. However, genetic analysis
      indicated the proportion of wild-type mtDNA was unchanged (3/9) or fell (6/9),
      suggesting a trend toward preferential proliferation of mutant genomes. The long
      term implications of training-induced increases in mutant relative to wild-type
      mtDNA, despite positive physiological and biochemical findings, need to be
      assessed before aerobic training can be proposed as a general treatment option.

PMID- 11506395
TI  - Metabolic enzyme expression in dopaminergic neurons in Parkinson's disease: an in
      situ hybridization study.
AB  - To clarify the role of neuronal complex 1 activity in idiopathic Parkinson's
      disease (IPD), expression of mitochondrial mRNA encoding the ND1 subunit of
      mitochondrial complex I was examined by semiquantitative in situ hybridization
      histochemistry in melanized neurons of human substantia nigra in IPD cases and
      control subjects. Expression of mRNA encoding the glycolytic enzyme, aldolase C,
      was also examined in substantia nigra and other neurons of the midbrain and brain
      stem. ND1 mRNA expression was strong in melanized substantia nigra neurons but
      undetectable in nigral glia. Levels of expression in nigral neurons were higher
      than in neurons of the red nucleus or cranial nerve nuclei, but similar values
      were obtained in pontine neurons. ND1 mRNA expression was reduced by about 25% in
      melanized neurons in IPD. There was no relationship between ND1 expression per
      cell and disease duration or L-DOPA dosage in the IPD group. No change in ND1
      expression was observed in pontine neurons in IPD, and ND1 expression in the
      locus ceruleus was also unchanged. Melanized nigral neurons expressed lower
      levels of aldolase C mRNA than other midbrain or brain stem populations in both
      control and IPD material. These findings suggest that dopamine neurons are more
      strongly dependent on mitochondrial energy metabolism and oxidative
      phosphorylation than other brain stem populations. Because mitochondrial complex
      I activity is significantly reduced in IPD, intrinsically low expression of
      glycolytic enzymes, together with disease-related reduction in complex I
      activity, may be a contributory factor predisposing nigral neurons

PMID- 11506397
TI  - Increased frequency of the tumor necrosis factor-alpha-308 A allele in adults
      with human immunodeficiency virus dementia.
AB  - Genetic polymorphisms in the regulatory regions of various cytokine genes
      influence the amount of cytokine produced in response to inflammatory stimuli. To
      determine whether such polymorphisms might play a role in human immunodeficiency
      virus (HIV) dementia, a disease process in which tumor necrosis factor (TNF)
      alpha is believed to play a role, we analyzed HIV-infected adults with and
      without dementia and control populations for a polymorphic site located in the
      promoter region of the gene coding for TNF-alpha. The presence of the A allele at
      the TNF-alpha-308 site was overrepresented among adults with HIV dementia
      compared to those without dementia (0.28 vs 0.07; OR 5.5; 95% CI 1.8-17.0) and a
      healthy control population (0.28 vs 0.11). The increased frequency of the A
      allele in HlV-infected adults with dementia suggests that this locus may play a
      role in the pathophysiology of dementia and suggests a genetic predisposition for
      the development of HIV dementia.

PMID- 11506396
TI  - Large-scale, multicenter study of cerebrospinal fluid tau protein phosphorylated
      at serine 199 for the antemortem diagnosis of Alzheimer's disease.
AB  - We surveyed a total of 570 cerebrospinal fluid (CSF) samples from a variety of
      diseases, including Alzheimer's disease (AD; n = 236), non-AD-demented and
      nondemented diseases (n = 239), and normal controls (n = 95) to quantitate levels
      of tau protein phosphorylated at serine 199 (CSF/phospho-tau199) by a recently
      established sandwich ELISA. The CSF/phospho-tau199 levels in the AD group were
      significantly elevated compared to those in all the other non-AD groups. Receiver
      operating characteristics curves showed that the diagnostic sensitivity and
      specificity for the AD group vs all the other non-AD groups using the CSF/phospho
      tau199 were 85.2% and 85.0%, respectively. Furthermore, there was a significant
      positive correlation between CSF/phospho-tau199 and CSF/total-tau levels in the
      AD group. Elevated CSF/phospho-tau199 in the AD group was noted irrespective of
      age, gender, dementia severity, and number of apolipoprotein E4 alleles. Thus, we
      suggest that CSF/phospho-tau199 may be a novel and logical biomarker in
      supporting antemortem diagnosis of AD.

PMID- 11506398
TI  - Presumed pre- or perinatal arterial ischemic stroke: risk factors and outcomes.
AB  - A subgroup of children with arterial ischemic stroke in the pre- or perinatal
      period present with delayed diagnosis. We identified 22 children who met the
      following criteria: (1) normal neonatal neurological history, (2) hemiparesis
      and/or seizures first recognized after two months of age, and (3) computed
      tomography or magnetic resonance imaging showing remote cerebral infarct.
      Laboratory evaluations included protein C, protein S, antithrombin, activated
      protein C resistance screen (APCR), Factor V Leiden (FVL), prothrombin gene
      defect, methylene tetrahydrofolate reductase variant (MTHFR), anticardiolipin
      antibody (ACLA), and lupus anticoagulant. Not all children received all tests.
      Age at last visit ranged from 8 months to 16.5 years (median 4 years). Twelve
      were boys. Fourteen had left hemisphere infarcts. Median age at presentation was
      6 months. Eighteen had gestational complications. Fourteen children had at least
      transient coagulation abnormalities (ACLA = 11, ACLA + APCR = 1, APCR = 2 with
      FVL + MTHFR = 1); six of these children had family histories suggestive of
      thrombosis. Cardiac echocardiogram was unremarkable in the 15 tested. Outcomes
      included persistent hemiparesis in 22; speech, behavior, or learning problems in
      12; and persistent seizures in five, with no evidence of further stroke in any
      patient. The persistence and importance of coagulation abnormalities in this
      group need further study.

PMID- 11506399
TI  - Multiple sclerosis: altered glutamate homeostasis in lesions correlates with
      oligodendrocyte and axonal damage.
AB  - Glutamate excitotoxicity, recently demonstrated in an animal model of multiple
      sclerosis (MS), is evoked by altered glutamate homeostasis. In the present study,
      we investigated the major regulating factors in glutamate excitotoxicity by
      immunohistochemistry in MS and control white matter with markers for glutamate
      production (glutaminase), glutamate transport (GLAST, GLT-1 and EAAT-1),
      glutamate metabolism (glutamate dehydrogenase [GDH] and glutamine synthetase
      [GS]), axonal damage (SMI 32) and CNS cell types. Active MS lesions showed high
      level glutaminase expression in macrophages and microglia in close proximity to
      dystrophic axons. Correlation between glutaminase expression and axonal damage
      was confirmed experimentally in animals. White matter from other inflammatory
      neurologic diseases displayed glutaminase reactivity, whereas normals and
      noninflammatory conditions showed none. All three glutamate transporters were
      expressed robustly, mainly on oligodendrocytes, in normal, control and MS white
      matter, except for GLT-1, which showed low-level expression around active MS
      lesions. GS and GDH were present in oligodendrocytes in normal and non-MS white
      matter but were absent from both active and chronic silent MS lesions, suggesting
      lasting metabolic impediments. Thus, imbalanced glutamate homeostasis contributes
      to axonal and oligodendroglial pathology in MS. Manipulation of this imbalance
      may have therapeutic import.

PMID- 11506400
TI  - Blinded positron emission tomography study of dopamine cell implantation for
      Parkinson's disease.
AB  - We assessed nigrostriatal dopaminergic function in Parkinson's disease (PD)
      patients undergoing a double-blind, placebo-controlled surgical trial of
      embryonic dopamine cell implantation. Forty PD patients underwent positron
      emission tomography (PET) imaging with [18F]fluorodopa (FDOPA) prior to
      randomization to transplantation or placebo surgery. The 39 surviving patients
      were rescanned one year following surgery. Images were quantified by
      investigators blinded to treatment status and clinical outcome. Following
      unblinding, we determined the effects of treatment status and age on the interval
      changes in FDOPA/PET signal. Blinded observers detected a significant increase in
      FDOPA uptake in the putamen of the group receiving implants compared to the
      placebo surgery patients (40.3%). Increases in putamen FDOPA uptake were similar
      in both younger (age < or = 60 years) and older (age > 60 years) transplant
      recipients. Significant decrements in putamen uptake were evident in younger
      placebo-operated patients (-6.5%) but not in their older counterparts.
      Correlations between the PET changes and clinical outcome were significant only
      in the younger patient subgroup (r = 0.58). The findings suggest that patient age
      does not influence graft viability or development in the first postoperative
      year. However, host age may influence the time course of the downstream
      functional changes that are needed for clinical benefit to occur.

PMID- 11506401
TI  - Brain-derived neurotrophic factor enhances fast excitatory synaptic transmission
      in human epileptic dentate gyrus.
AB  - Brain-derived neurotrophic factor (BDNF) has trophic effects and modulates
      synaptic transmission in the hippocampal formation in animal studies. It is also
      upregulated in acute and chronic epilepsy models and in human temporal lobe
      epilepsy. This study was undertaken to examine the effects of BDNF on fast
      synaptic transmission in the human epileptic dentate gyrus. Hippocampal specimens
      were acquired from patients with temporal lobe epilepsy during surgical removal
      of the anterior temporal lobe intended to treat the epileptic condition. Whole
      cell patch-clamp recordings were obtained from dentate granule cells in
      transverse hippocampal slices in vitro. Application of BDNF increased the
      amplitude and frequency of spontaneous excitatory postsynaptic currents and
      increased the amplitude of evoked excitatory postsynaptic currents. BDNF had no
      effect on spontaneous inhibitory postsynaptic currents but produced a decrease in
      amplitude of evoked inhibitory postsynaptic currents. BDNF's effects were
      abolished by coapplication of the tyrosine kinase inhibitor K252a. Therefore,
      BDNF enhances fast excitatory transmission in the epileptic human dentate gyrus
      and may play an important role in epileptogenesis in temporal lobe epilepsy. This
      raises the possibility of designing therapies for this disorder that may be both
      anticonvulsant and antiepileptogenic.

PMID- 11506402
TI  - Randomized controlled trial of intravenous immunoglobulin versus oral
      prednisolone in chronic inflammatory demyelinating polyradiculoneuropathy.
AB  - This multicenter, randomized, double-blind, crossover trial compared a six week
      course of oral prednisolone tapering from 60 mg to 10 mg daily with intravenous
      immunoglobulin (IVIg) 2.0 g/kg given over one to two days for treating chronic
      inflammatory demyelinating polyradiculoneuropathy (CIDP). Twenty-four of the
      thirty-two randomized patients completed both treatment periods. Both treatments
      produced significant improvements in the primary outcome measure, change in an 11
      point disability scale two weeks after randomization. There was slightly, but not
      significantly, more improvement after IVIg than with prednisolone, the mean
      difference between the groups in change in disability grade being 0.16 (95% CI = 
      0.35 to 0.66). There were also slightly, but not significantly, greater
      improvements favoring IVIg in the secondary outcome measures: time to walk 10
      meters after two weeks and improvement in disability grade after six weeks.
      Results may have been biased against IVIg by the eight patients who did not
      complete the second arm of the trial. A serious adverse event (psychosis)
      attributable to treatment occurred in one patient while on prednisolone and in
      none with IVIg.

PMID- 11506403
TI  - Beta-enolase deficiency, a new metabolic myopathy of distal glycolysis.
AB  - A severe muscle enolase deficiency, with 5% of residual activity, was detected in
      a 47-year-old man affected with exercise intolerance and myalgias. No rise of
      serum lactate was observed with the ischemic forearm exercise. Ultrastructural
      analysis showed focal sarcoplasmic accumulation of glycogen beta particles. The
      enzyme enolase catalyzes the interconversion of 2-phosphoglycerate and
      phosphoenolpyruvate. In adult human muscle, over 90% of enolase activity is
      accounted for by the beta-enolase subunit, the protein product of the ENO3 gene.
      The beta-enolase protein was dramatically reduced in the muscle of our patient,
      by both immunohistochemistry and immunoblotting, while alpha-enolase was normally
      represented. The ENO3 gene of our patient carries two heterozygous missense
      mutations affecting highly conserved amino acid residues; a G467A transition
      changing a glycine residue at position 156 to aspartate, in close proximity to
      the catalytic site, and a G1121A transition changing a glycine to glutamate at
      position 374. These mutations were probably inherited as autosomal recessive
      traits since the mother was heterozygous for the G467A and a sister was
      heterozygous for the G1121A transition. Our data suggest that ENO3 mutations
      result in decreased stability of mutant beta-enolase. Muscle beta-enolase
      deficiency should be considered in the differential diagnosis of metabolic
      myopathies due to inherited defects of distal glycolysis.

PMID- 11506404
TI  - Imaging appearance of the symptomatic perforating artery in patients with lacunar
      infarction: occlusion or other vascular pathology?
AB  - Lacunar infarction is associated with distinct clinical features. It is thought
      to result from occlusion of a deep perforating artery in the basal ganglia,
      centrum semiovale, or brain stem. However, occluded perforating arteries have
      only rarely been observed at postmortem in patients with lacunar stroke and have
      not been noted previously on imaging despite the increasing sophistication of the
      techniques. We observed nine patients with lacunar stroke imaged with computed
      tomography and magnetic resonance imaging in whom we observed a linear structure
      with density or signal features consistent with an occluded (or at least
      abnormal) perforating artery associated with the relevant lacunar infarct. The
      appearance might also have been caused by a leak of blood and fluid into the
      perivascular space around the artery, as in several patients the width of the
      tubular vessel-like structure (>1 mm in diameter) was greater than the expected
      width of a perforating artery (<0.8 mm in diameter). This interpretation is
      supported by the fact that the area of infarction was usually around the abnormal
      vessel, not at the end of it. We describe the patients' clinical and imaging
      features, and discuss alternative explanations for the imaging appearance and the
      implications for gaining insights into the cause of lacunar infarction.

PMID- 11506405
TI  - Chromogranins as markers of altered hippocampal circuitry in temporal lobe
      epilepsy.
AB  - Chromogranins are polypeptides which are widely expressed in the central nervous
      system. They are stored in dense core vesicles of nerve terminals, from where
      they are released upon stimulation. Using immunocytochemistry, we investigated
      the distribution of chromogranin A, chromogranin B, secretoneurin, and, for
      comparison, dynorphin in hippocampal specimens removed at routine surgery from
      patients with drug-resistant mesial temporal lobe epilepsy and in autopsy tissues
      from nonneurologically deceased subjects. In post mortem controls (n = 21),
      immunoreactivity for all 4 peptides (most prominently for chromogranin B and
      dynorphin) was observed in the terminal field of mossy fibers. For chromogranins,
      staining was observed also in sectors CA1 to CA3 and in the subiculum.
      Chromogranin B immunoreactivity was found in the inner molecular layer of the
      dentate gyrus, the area of terminating associational-commissural fibers.
      Secretoneurin and dynorphin immunoreactivity labeled the outer molecular layer
      and the stratum lacunosum moleculare of sectors CA1 to CA3, where projections
      from the entorhinal cortex terminate. In specimens with Ammon's horn sclerosis (n
      = 25), staining for all 3 chromogranins and for dynorphin was reduced in the
      hilus of the dentate gyrus. Instead, intense staining was observed in the inner
      molecular layer, presumably delineating terminals of sprouted mossy fibers.
      Specimens obtained from temporal lobe epilepsy patients without Ammon's horn
      sclerosis (n = 4) lacked this pronounced rearrangement of mossy fibers. In the
      stratum lacunosum moleculare of sector CA1, secretoneurin and dynorphin
      immunoreactivity was reduced in sclerotic, but not in nonsclerotic, specimens,
      paralleling the partial loss of fibers arising from the entorhinal cortex.
      Instead, presumably sprouted secretoneurin-immunoreactive fibers were found in
      the outer dentate molecular layer in sclerotic specimens. These changes in
      staining patterns for chromogranins and dynorphin mark profound plastic and
      functional rearrangement of hippocampal circuitry in temporal lobe epilepsy.

PMID- 11506406
TI  - Increased incidence of sporadic Creutzfeldt-Jakob disease on the island of Crete
      associated with a high rate of PRNP 129-methionine homozygosity in the local
      population.
AB  - Since the spring of 1997, when the Neurology Department of the University
      Hospital of Crete admitted its first patient, nine cases (eight
      neuropathologically confirmed and one probable) of sporadic Creutzfeldt-Jakob
      disease (sCJD) have been recorded. This represents an annual incidence five-fold
      higher than expected based on the island's population (0.54 million). Molecular
      analysis of the prion-protein gene (PRNP) showed no mutations in any of the seven
      CJD cases studied. Five patients (ages 64-88 years) were homozygous for
      methionine-129 of PRNP and showed the classic sCJD triad (subacute dementia,
      myoclonus, periodic electroencephalogram). Brains contained type 1
      (unglycosylated 21.5 kDa band) protease-resistant prion protein (PrPres). Two
      patients (ages 56 and 57 years), both homozygous for valine-129, showed
      cerebellar ataxia and later dementia not associated with periodic
      electroencephalogram; brain PrPres was type 2. Genotyping of 205 Cretan controls
      showed that methionine-129 homozygosity, a susceptibility factor for sCJD, was
      significantly higher in this population than in other Caucasian populations
      (57.0% n = 205 vs. 41.5% n = 859, p < 0.0001). These data are the first to relate
      a high regional incidence rate for sCJD to the distribution of PRNP 129 genotypes
      in the local population; however, additional factors may be operational.

PMID- 11506407
TI  - Clinical and genetic analysis of four Mexican families with spinocerebellar
      ataxia type 10.
AB  - Spinocerebellar ataxia type 10 (SCA10) is an autosomal dominant disorder caused
      by expansion of an unstable ATTCT repeat. SCA10 has been described as a pure
      cerebellar syndrome accompanied by seizures and has been recognized only in
      families of Mexican origin. We describe clinical and molecular findings of 18
      patients in four Mexican families with SCA10. Affected individuals had an average
      age at onset of 26.7 years (range 14-44 years) and ATTCT repeats ranging from 920
      to 4,140 repeats. We could not detect significant anticipation or correlation
      between repeat size and age at onset, probably due to the small sample size. In
      addition to pure cerebellar ataxia and seizures, patients often showed soft
      pyramidal signs, ocular dyskinesia, cognitive impairment, and/or behavioral
      disturbances. Brain magnetic resonance imaging showed predominant cerebellar
      atrophy, and nerve conduction studies indicated polyneuropathy in 66% of
      patients. One family showed hepatic, cardiac, and hematological abnormalities in
      affected members. These findings suggest that a wide range of tissues may be
      affected in SCA10, including those outside of the cerebellum and cerebral cortex.

PMID- 11506408
TI  - Reorganization of human motor cortex after hand replantation.
AB  - In 10 patients, reorganizational changes of the motor cortex contralateral to a
      replanted hand (MCreplant) were studied one to 14 years after complete traumatic
      amputation and consecutive successful replantation of the hand. The
      organizational state of MCreplant was assessed for the deafferentated and
      peripherally deefferentated hand-associated motor cortex and the adjacent motor
      representation of the proximal arm. For this, response maps were established for
      the first dorsal interosseus and biceps brachii muscle using focal transcranial
      magnetic stimulation (TMS) on a skull surface grid. Characteristics of the maps
      were center of gravity (COG), number of effective stimulation sites, amplitude
      sum, and amplitudes and response threshold at the optimal stimulation point. The
      COG is defined by the spatial distribution of response amplitudes on the map and
      lies over the cortex region with the most excitable corticospinal neurones
      supplying the recorded muscle. The COG of the biceps map in MCreplant was shifted
      laterally by 9.8 +/- 3.6 mm (range 5.0-15.7 mm). The extension of the biceps map
      in MCreplant was increased and the responses were enlarged and had lowered
      thresholds. For the muscles of the replanted hand, the pattern of reorganization
      was different: Response amplitudes were enlarged but thresholds, COG, and area of
      the cortical response map were normal. The different reorganizational phenomena
      observed for the motor cortical areas supplying the replanted hand and the biceps
      brachii of the same arm may be influenced by a different extent of
      deafferentation and by their different role in hand motor control.

PMID- 11506409
TI  - Nonprogressive autosomal recessive ataxia maps to chromosome 9q34-9qter in a
      large consanguineous Lebanese family.
AB  - Congenital ataxias are a heterogeneous group of predominantly nonprogressive
      disorders characterized by hypotonia, developmental delay followed by the
      appearance of ataxia, and often associated with dysarthria, mental retardation,
      and atrophy of the cerebellum. We performed a genome-wide screen on a large
      inbred Lebanese family presenting a nonprogressive autosomal recessive congenital
      cerebellar ataxia associated with short stature (MIM 213200), already described
      by Megarbane and colleagues. The disease locus was assigned to a 12.1 cM interval
      on chromosome 9q34-9qter between D9S67 and D9S312. Differential diagnosis with
      other hereditary ataxias linked to the same region is discussed.

PMID- 11506410
TI  - Levodopa induces dyskinesias in normal squirrel monkeys.
AB  - This study assessed whether or not levodopa induces dyskinesias in normal (ie,
      unlesioned) squirrel monkeys. All six animals treated twice daily with levodopa
      (15 mg/kg with carbidopa by oral gavage) for two weeks developed choreoathetoid
      dyskinesias, whereas none of the vehicle-treated animals displayed any abnormal
      movements. These dyskinesias did not merely reflect a generalized motor
      activation as locomotion was actually suppressed. The present data demonstrate
      that preexisting nigrostriatal damage is not necessary for the development of
      levodopa-induced dyskinesias.

PMID- 11506411
TI  - Sporadic Creutzfeldt-Jakob disease in a young Dutch valine homozygote: atypical
      molecular phenotype.
AB  - A case of sporadic Creutzfeldt-Jakob disease (sCJD) is described in a young Dutch
      protein prion gene (PRNP) codon 129 valine homozygote. Certain clinical and
      molecular features of this case overlap those of variant CJD. The case highlights
      possible difficulties in the differential diagnosis of vCJD and the more rare
      sCJD subtypes based on molecular features alone.

PMID- 11506412
TI  - Frameshift mutation in the collagen VI gene causes Ullrich's disease.
AB  - Patients with Ullrich's disease have generalized muscle weakness, multiple
      contractures of the proximal joints, and hyperextensibility of the distal joints.
      Recently, we found a deficiency of collagen VI protein in two patients with
      Ullrich's disease. In this study, we detected a homozygous 26 bp deletion in exon
      14 of the collagen VI alpha 2 gene (COL6A2) in one patient. This mutation causes
      a frameshift and a premature termination codon, and results in a truncated
      collagen VI alpha 2 chain. Our data suggest that at least some cases of Ullrich's
      disease result from recessive mutations in COL6A2.

PMID- 11506413
TI  - Proton magnetic resonance spectroscopy of brain metabolites in galactosemia.
AB  - Brain edema may occur in infants with galactosemia and has been associated with
      accumulation of galactitol. Proton magnetic resonance spectra were obtained from
      12 patients (four newly diagnosed neonates and eight patients on galactose
      restricted diets, age range 1.7-47 years) and control subjects to measure brain
      galactitol levels in vivo and correlate them with urinary galactitol excretion.
      The results demonstrate that a markedly elevated brain galactitol level may be
      present only in newborn infants with galactosemia who exhibit massive urinary
      galactitol excretion.

PMID- 11506414
TI  - Adult neuronal ceroid lipofuscinosis with palmitoyl-protein thioesterase
      deficiency: first adult-onset patients of a childhood disease.
AB  - The fluorogenic enzyme assay for palmitoyl-protein thioesterase (PPT) has greatly
      facilitated the diagnosis of infantile neuronal ceroid lipofuscinosis (Santavuori
      Haltia disease) and the search for possible new variants with atypical clinical
      presentation. Here, we present the first cases of adult neuronal ceroid
      lipofuscinosis with onset in the fourth decade of life due to a profound
      deficiency of PPT. The causative mutations in the CLN1 gene were the known,
      deleterious mutation R151X and the novel missense mutation G108R. Patients
      presented at onset (31 and 38 years), with psychiatric symptoms only. At present
      (ages 56 and 54 years), visual, verbal, and cognitive losses have progressed and
      both patients have cerebellar ataxia and cannot walk without support.

PMID- 11506415
TI  - Survival in a transgenic model of FALS is independent of iNOS expression.

PMID- 11506416
TI  - Herpes simplex virus type 1-induced acute retinal necrosis.

PMID- 11506417
TI  - Interleukin-12p40 genotype plays a role in the susceptibility to multiple
      sclerosis.

PMID- 11506418
TI  - Polymorphism of the interleukin-1 gene complex in localization-related epilepsy.

PMID- 11506419
TI  - Conflict of interest and its significance in science and medicine: a view from
      Eastern Europe.

PMID- 11506420
TI  - Learning from the law to address uncertainty in the precautionary principle.
AB  - Environmentalists have advocated the Precautionary Principle (PP) to help guide
      public and private decisions about the environment. By contrast, industry and its
      spokesmen have opposed this. There is not one principle, but many that have been
      recommendedfor this purpose. Despite the attractiveness of a core idea in all
      versions of the principle--that decision-makers should take some precautionary
      steps to ensure that threats of serious and irreversible damage to the
      environment and public health do not materialize into harm--even one of the most
      widely endorsed principles needs considerable specification and refinement before
      it can be used. Moreover, the PP is an approach or guide to utilizing scientific
      evidence in social or legal decision-making contexts. In this it does not differ
      in kind from other approaches to using factual information such as in the law.
      The law provides some models for different strategies to guide decision-making
      under uncertainty when factual issues cannot be resolved with certainty. These in
      turn can help guide the formulation of different versions of PP and help clarify
      some presuppositions of the principle. Once some plausible versions of PP are
      articulated, I suggest some applications to existing environmental problems.

PMID- 11506421
TI  - The debate over food biotechnology in the United States: is a societal consensus
      achievable?
AB  - Unless the public comes to agree that the benefits of food biotechnology are
      desirable and the associated risks are acceptable, our society may fail to
      realize much of the potential benefits. Three historical cases of major
      technological innovations whose benefits and risks were the subject of heated
      public controversy are examined, in search of lessons that may suggest a path
      toward consensus in the biotechnology debate. In each of the cases--water
      fluoridation, nuclear power and pesticides--proponents of the technology gathered
      scientific evidence that they believed established that the innovations were
      safe. In each case, the federal government was heavily involved in oversight,
      safety regulation, and in the first two cases, active promotion of the
      technology. Supporters of the technologies employed a variety of communications
      strategies, ranging from massive "educational" campaigns (e.g. "Our Friend The
      Atom") to vituperative ad hominem attacks on leading opponents. None of these
      strategies succeeded in achieving broad societal acceptance of the technologies.
      Fluoridation today is opposed as vigorously by activist groups as it was when
      first introduced around 1950; it has not been universally adopted even in the
      U.S., and it has been rejected in most other countries. The American nuclear
      power industry is moribund, and the public has essentially rejected the
      technology. The pesticide industry is thriving, with new generations of products
      succeeding older more hazardous chemicals in a constant cycle. However, strong
      regulation has failed to prevent adverse health and ecological effects, which
      have been empirically associated with pesticide uses after the chemicals were
      dispersed in the environment. Debate over whether risks of such effects are
      acceptable has been heated for four decades, with scientists and the public
      divided.

PMID- 11506422
TI  - Serious misapplications of military research: dysfunction between conception and
      implementation.
AB  - Researchers and technologists involved in the development of weapon systems can
      take their work to such extremes as to cause unplanned injury or death to others
      and lasting damage to the environment, reviewed here. In some cases innocent
      human casualties and ecological harm may actually be programmed and achieved. An
      analysis is proffered, attributing blame, and indicating efforts to correct the
      situation. The ethics involved are "complexified",a moral boundaries are
      exceeded, and humanity is transgressed as it develops solutions to the problem.

PMID- 11506423
TI  - Towards a research programme for ethics and technology.
AB  - In this editorial contribution, two issues relevant to the question, what should
      be at the top of the research agenda for ethics and technology, are identified
      and discussed. Firstly: can, and do, engineers make a difference to the degree to
      which technology leads to morally desirable outcomes? What role does professional
      autonomy play here, and what are its limits? And secondly, what should be the
      scope of engineers' responsibility; that is to say, on which issues are they, as
      engineers, morally obliged to reflect? The research agendas proposed by the
      authors contributing to this special section, implicitly, give different answers
      to these questions. We suggest that an explicit discussion of these issues would
      greatly help in constructing a common research agenda.

PMID- 11506424
TI  - The professional approach to engineering ethics: five research questions.
AB  - This paper argues that research for engineering ethics should routinely involve
      philosophers, social scientists, and engineers, and should focus for now on
      certain basic questions such as: Who is an engineer? What is engineering? What do
      engineers do? How do they make decisions? And how much control do they actually
      have over what they do?

PMID- 11506425
TI  - Responsible engineering: the importance of character and imagination.
AB  - Engineering Ethics literature tends to emphasize wrongdoing, its avoidance, or
      its prevention. It also tends to focus on identifiable events, especially those
      that involve unfortunate, sometimes disastrous consequences. This paper shifts
      attention to the positive in engineering practice; and, as a result, the need for
      addressing questions of character and imagination becomes apparent.

PMID- 11506426
TI  - Future directions in engineering ethics research: microethics, macroethics and
      the role of professional societies.
AB  - Three frames of reference for engineering ethics are discussed--individual,
      professional and social--which can be further broken down into "microethics"
      concerned with individuals and the internal relations of the engineering
      profession and "macroethics" referring to the collective social responsibility of
      the engineering profession and to societal decisions about technology. Few
      attempts have been made at integrating microethical and macroethical approaches
      to engineering ethics. The approach suggested here is to focus on the role of
      professional engineering societies in linking individual and professional ethics
      and in linking professional and social ethics. A research program is outlined
      using ethics support as an example of the former, and the issuance of position
      statements on product liability as an example of the latter.

PMID- 11506427
TI  - The application of ethics to engineering and the engineer's moral responsibility:
      perspectives for a research agenda.
AB  - There are different possibilities for defining the areas for the application of
      ethics to engineering. They range from descriptive analysis of engineers'
      relationship to moral criteria and extend to normative issues on how engineers
      should design more "sustainable" technology. In this paper, a frame of reference
      is proposed, which makes it possible to elaborate in a transparent manner goals
      for analysis of the scope of ethics in engineering Its point of departure is
      marked by two questions. 1) which types of situation in the practice of
      engineering require ethical reflection? and 2) to what extent are engineers
      expected to assume moral responsibility in the practice of their profession? The
      answers to both of these questions presuppose reflection on the societal
      processes of setting definitions and of making ascriptions. Understanding these
      processes of societal "construction" of demands for ethical reflection in
      engineering and of engineers' moral responsibilities should be an important
      objective of the analysis of ethics in engineering.

PMID- 11506428
TI  - Investigating ethical issues in engineering design.
AB  - This paper aims at contributing to a research agenda in engineering ethics by
      exploring the ethical aspects of engineering design processes. A number of
      ethically relevant topics with respect to design processes are identified. These
      topics could be a subject for further research in the field of engineering
      ethics. In addition, it is argued that the way design processes are now organised
      and should be organised from a normative point of view is an important topic for
      research.

PMID- 11506429
TI  - Methodological issues in size estimation of myelinated nerve fibers in peripheral
      nerves.
AB  - Size estimation of myelinated nerve fibers in peripheral nerves is a very common
      task in neuromorphology and different dedicated morpho-quantitative procedures
      have been devised and used to date. Unfortunately, many reports on experimental
      nerve studies lack comprehensive information on the procedures that have been
      designed and applied for myelinated fiber size estimation. This paper addresses
      the issue in the light of the recent advances in quantitative morphology that
      have recognized the concept of unbiased estimates as the key methodological issue
      to be addressed in morpho-quantitative studies. The potential foundations of bias
      at various study levels are analysed together with indications on how to cope
      with them. In addition, the issue of the precision of size estimates is addressed
      and the various geometrical parameters that can be selected for myelinated nerve
      fiber size assessment are outlined. Taken together, information provided in this
      paper is expected to help investigators conduct an appropriate preliminary study
      design phase, the key step for setting up the most adequate morpho-quantitative
      procedure for any given research goal.

PMID- 11506430
TI  - C-Kit mutant mice have a selective loss of vagal intramuscular mechanoreceptors
      in the forestomach.
AB  - Intramuscular arrays are one of two major classes of vagal afferent
      mechanoreceptors that innervate the smooth muscle wall of the proximal
      gastrointestinal tract. They consist of rectilinear telodendria that distribute
      in the muscle sheets, parallel to the long axes of muscle fibers. Intramuscular
      arrays appear to make direct contact with the muscle fibers, but they also course
      on, and form appositions with, intramuscular interstitial cells of Cajal. These
      complexes formed by intramuscular arrays and intramuscular interstitial cells of
      Cajal suggest that intramuscular arrays might require either structural or
      trophic support of the interstitial cells of Cajal for normal differentiation
      and/or maintenance. To evaluate this hypothesis, we have examined the morphology
      and distribution of vagal afferent endings in the c-Kit mutant mouse that lacks
      intramuscular interstitial cells of Cajal. Vagal afferents were labeled by nodose
      ganglion injection of either wheat germ agglutinin-horseradish peroxidase
      conjugate or a tagged dextran, and the labeled afferent terminals in the stomach
      were mapped using a standardized quantitative sampling scheme. Intramuscular
      arrays were dramatically reduced (in circular muscle by 63%; in longitudinal
      muscle by 78%) in the c-Kit mutant mice relative to their wild-type littermates.
      Additionally, a substantial number of the surviving axons and terminals in the
      mutant stomachs were morphologically aberrant. Moreover, the loss of
      intramuscular arrays in mutants appeared to be selective: the structure,
      distribution and density of intraganglionic laminar endings, i.e., the other
      vagal mechanoreceptors in smooth muscle, were not significantly altered. Finally,
      the conspicuous decrease in intramuscular array density in mutants was associated
      with a non-significant trend toward loss of nodose ganglion neurons. Collectively
      these findings suggest that interstitial cells are required for the normal
      development or maintenance of vagal intramuscular arrays. Therefore, the c-Kit
      mutant mouse will be valuable for determining the role(s) of interstitial cells
      in intramuscular array development as well as for providing an animal model with
      the intramuscular array class of vagal afferents selectively ablated.

PMID- 11506431
TI  - Distribution of BDNF, NT-3, trkB and trkC in the developing retino-tectal system
      of the pigeon (Columba livia).
AB  - The distribution of the neurotrophins BDNF and NT-3 as well as their
      corresponding high-affinity receptors trkB and trkC was characterized by
      immunohistochemistry in the developing retino-tectal system of the pigeon. These
      neurotrophins are known to be important for survival and development of neuronal
      tissues, but also for activity-dependent neuronal plasticity. In pigeons visual
      asymmetry is established at the morphological and behavioral level due to a
      natural asymmetrical light input before hatch, which is followed by a posthatch
      period of consolidation with unbiased light stimulation. Since the retino-tectal
      system is the crucial entity of these events, we studied the retinal and the
      tectal distribution of these neurotrophins and their receptors during retino
      tectal formation, to analyze the developmental sequences to which these
      neurotrophins are tuned. Here we demonstrate that in altricial pigeons no retinal
      immunolabeling of BDNF, NT-3 or their receptors could be detected before hatch,
      although a prominent tectal labeling pattern throughout most layers was evident.
      After hatch, both neurotrophins and their receptors showed a dramatic increase of
      retinal and tectal distribution. While the tectal and retinal protein synthesis
      of NT-3 vanished after 2 weeks, that of BDNF could still be revealed in adults.
      Therefore, the establishment of the retino-tectal system does not seem to depend
      on these neurotrophins before hatch, although they are probably utilized to shape
      the intratectal wiring pattern. In contrast, BDNF and NT-3 could play a prominent
      role in posthatch retino-tectal plasticity, as the consolidation of tectal
      asymmetries requires posthatch modifications of tectal circuits and proceeds
      within the first two posthatching weeks. These data are comparable with the
      distribution of neurotrophins in the retino-tectal system of chicks, although the
      onset of neurotrophin synthesis seems to be earlier in precocial chicks.

PMID- 11506432
TI  - Development of the digestive tract of sea bass (Dicentrarchus labrax L). Light
      and electron microscopic studies.
AB  - The developing gut of sea bass was studied by light and electron microscopy, four
      phases being established. Phase I, from hatching to the opening of the mouth, was
      a lecitotrophic period, in which the gut appeared as a straight undifferentiated
      tube lined by a simple epithelium that became stratified in the most caudal
      region. The epithelial cells increased in length towards the caudal zone, as did
      the number and height of the apical microvilli and the magnitude of the lamellar
      structures in their basal region. Cilia were more numerous in the caudal region
      than in the rest of the gut. Signs of lipid but not of protein absorption were
      found in the epithelial cells at this phase. Phase II, from the opening of the
      mouth to the complete resorption of the yolk sac, was a lecitoexotrophic period
      in which an esophagus, a gastric region, an intestine and a rectum, the last two
      separated by a valve, were present. During this phase the differentiation of the
      gut started at the esophagus and the rectum. In the esophagus, the epithelium
      became stratified and goblet cells containing acid mucosubstances, including
      sulphomucins, appeared. In the epithelial cells of the rectum, supranuclear
      vacuoles and an incipient endocytotic apparatus that seemed to be involved in the
      absorption and digestion of proteins were found. In both regions the mucosa was
      folded. Phase III, from the complete resorption of the yolk sac to the appearance
      of the first gastric glands, initiated the exclusively exotrophic period. During
      this phase the intestine formed the mucosa folds, while the first pyloric caeca
      and the epithelial cells acquired the ultrastructural features of mature
      absorptive cells with many lipid inclusions. Goblet cells containing neutral
      mucosubstances appeared and increased in number in both the intestine and the
      rectum. Neutral mucosubstances were also present in the cells lining the gastric
      region. During phase IV, from the appearance of the first gastric glands onwards,
      the intestinal absorptive surface increased with the formation of new pyloric
      caeca and two intestinal loops. The stomach acquired its definitive anatomy and
      histology with the development of the caecal and pyloric regions alongside
      differentiated gastric glands. The glandular cells had the ultrastructural
      features of the cells that secrete both pepsinogen and hydrochloride acid in the
      adult teleost stomach.

PMID- 11506433
TI  - GFAP-immunopositive structures in spiny dogfish, Squalus acanthias, and little
      skate, Raia erinacea, brains: differences have evolutionary implications.
AB  - GFAP expression patterns were compared between the brains of a spiny dogfish
      (Squalus acanthias) and a little skate (Raia erinacea). After anesthesia, the
      animals were perfused with paraformaldehyde. Serial vibratome sections were
      immunostained against GFAP using the avidin-biotin method. Spiny dogfish brain
      contained mainly uniformly-distributed, radially arranged ependymoglia. From GFAP
      distribution, the layered organization in both the telencephalon and the tectum
      were visible. In the cerebellum, the molecular and granular layers displayed
      conspicuously different glial structures; in the former a Bergmann glia-like
      population was found. No true astrocytes (i.e., stellate-shaped cells) were
      found. Radial glial endfeet lined all meningeal surfaces. Radial fibers also
      seemed to form endfeet and en passant contacts on the vessels. Plexuses of fine
      perivascular glial fibers also contributed to the perivascular glia. Compared
      with spiny dogfish brain, GFAP expression in the little skate brain was confined.
      Radial glia were limited to a few areas, e.g., segments of the ventricular
      surface of the telencephalon, and the midline of the diencephalon and
      mesencephalon. Scarce astrocytes occurred in every brain part, but only the optic
      chiasm, and the junction of the tegmentum and optic tectum contained large
      numbers of astrocytes. Astrocytes formed the meningeal glia limitans and the
      perivascular glia. No GFAP-immunopositive Bergmann glia-like structure was found.
      Astrocytes seen in the little skate were clearly different from the mammalian and
      avian ones; they had a different process system - extra large forms were
      frequently seen, and the meningeal and perivascular cells were spread along the
      surface instead of forming endfeet by processes. The differences between Squalus
      and Raia astroglia were much like those found between reptiles versus mammals and
      birds. It suggests independent and parallel glial evolutionary processes in
      amniotes and chondrichthyans, seemingly correlated with the thickening of the
      brain wall, and the growing complexity of the brain. There is no strict
      correlation, however, between the replacement of radial ependymoglia with
      astrocytes, and the local thickness of the brain wall.

PMID- 11506434
TI  - Neuroarchitecture of the auditory cortex in the rufous horseshoe bat (Rhinolophus
      rouxi).
AB  - This study describes the location and anatomical subdivisions of the auditory
      cortex of the horseshoe bat, Rhinolophus rouxi. The basic cyto- and
      myeloarchitectural features and cytochrome oxidase reactivity patterns are
      evaluated in brains where auditory fields have been previously established
      neurophysiologically (Radtke-Schuller and Schuller 1995). Thus, the
      neuroanatomical findings from these brains and additional analyzed material are
      related to neurophysiological characteristics. The neocortex of Rhinolophus shows
      a typical mammalian six-layered organization. It is poorly laminated, has a low
      density of granular elements, a wide layer I, and a phylogenetically old
      pyramidal cell type in a sharply accentuated layer II. These features are
      generally considered 'primitive' or conservative. Frontal, parietal, temporal and
      occipital regions can be distinguished. In the temporal cortex, layers III and IV
      are found to be markedly thicker than layer V, in contrast to the parietal
      region, where a prominent layer V, containing a high concentration of large
      pyramidal cells is the most outstanding feature. The entire temporal region, most
      of the parietal and parts of the occipital region are responsive to auditory
      stimuli. The primary auditory field corresponds to most of the temporal region.
      The fields of the parietal region almost completely coincide with the dorsal
      fields of the auditory cortex. Border zones between the temporal, parietal, and
      occipital regions correspond to the posterior auditory field. The non-primary
      fields of the auditory cortex occupy a larger area of the bat's neocortex than
      the primary field. The accentuated neuroarchitectural features, like cortical
      thickness and staining intensity, are shown to coincide with the physiological
      representation of biologically significant parameters.

PMID- 11506435
TI  - Contact lens research: 2000.

PMID- 11506436
TI  - Variable tinted spectacle lenses: a comparison of aesthetics and visual
      preference.
AB  - PURPOSE: To determine the correlation between the aesthetics of lens tints
      preferred for cosmesis and lens tints preferred for viewing. METHODS: Thirty-five
      subjects (mean age: 25; 49% male, 51% female) with no significant ocular
      pathology participated in the study. Median visual acuity was 20/20. Color vision
      testing was performed on each subject using Ishihara plates, and those with
      abnormal scores were excluded from the study. Subjects were shown nine pre
      selected tinted lenses (50% transmittance) of variable wavelengths. These lenses
      were mounted on two separate color backgrounds, one white and the other
      approximating their skin tone. Subjects were asked to choose from each background
      which tinted lens they would most prefer to wear and which lens they would least
      prefer to wear. The subjects were then shown a series of eight pictures (four
      nature photographs and four paintings) with different dominant wavelengths.
      Subjects were asked to grade the aesthetic effect of a clear lens and each of the
      nine tinted lenses on the appearance of the pictures. Chromaticity coordinates
      were calculated for each lens and picture. RESULTS: The blue lens was the most
      frequently chosen preferred lens to wear, followed by green, purple, and gray.
      The least preferred lenses were yellow, brown, and pink. For viewing the nature
      photographs, the clear lens was preferred over any of the tinted lenses. For
      viewing the paintings, the purple lens was most preferred. The yellow lens was
      least preferred for both photographs and paintings. CONCLUSIONS: Younger
      individuals with no significant ocular pathology preferred viewing both nature
      photographs and paintings through tinted lenses that did not, or only slightly,
      altered the chromaticity of the image. Whereas a clear lens was favored over the
      tinted lenses for viewing the photographs, some tinted lenses (purple and pink)
      were preferred for viewing paintings. There was no correlation between the most
      favored lens tint chosen based purely on cosmesis and the most favored lens tint
      based on viewing preference. However, the least preferred lens tint for cosmesis
      and viewing was yellow.

PMID- 11506437
TI  - Seven-day extended wear and 30-day continuous wear of high oxygen
      transmissibility soft silicone hydrogel contact lenses: a randomized 1-year study
      of 504 patients.
AB  - PURPOSE: To compare the performance and complication rates of PureVision (Bausch
      & Lomb, Inc.) high Dk/t silicone hydrogel lenses in 30-day continuous wear and 7
      day extended wear. METHODS: Five-hundred four (504) patients were randomized to
      30-day continuous wear (353 patients) or to 7-day extended wear (151 patients)
      and followed for 12 months. RESULTS: Eighty percent of patients did not report
      any symptoms/complaints at the follow-up exams. There were no cases of microbial
      keratitis. The annual incidence of the four most common clinically significant
      positive slit lamp findings related to lens wear for the 30-day and the 7-day
      groups, respectively, were as follows: corneal staining, 10.5% and 10.6%; corneal
      infiltrates, 4.6% and 2.3%; slight epithelial edema, 2.0% and 3.6%; and tarsal
      conjunctival abnormalities, 1.6% and 3.0%. There was no significant difference in
      complication rates between the groups. For reasons related to lens wear, 7.6% in
      the 30-day group and 13.2% in the 7-day group were dropped from the study. The
      patients' subjective judgment of comfort, visual quality, freedom from dryness,
      and lens handling varied from 89 to 95 on a scale of 0 to 100. The success rate
      was 82.9%, slightly better for the 30-day group (84.4%) than for the 7-day group
      (79.5%). CONCLUSION: The complication rate was low. Sight-threatening events,
      such as bacterial keratitis did not occur. Inflammatory changes were seen,
      although at a low rate. Anterior segment changes related to hypoxia were minimal.
      Limbal and bulbar hyperemiadecreased significantly after switching patients to
      PureVision lenses. There was no significant difference in complication rates
      between the 30-day group and the 7-day group.

PMID- 11506439
TI  - Oxygen tension beneath piggyback contact lenses and clinical outcomes of users.
AB  - PURPOSE: Patients with keratoconus sometimes wear a rigid contact lens as a
      piggyback over a countersunk soft one. This geometry restricts movement of the
      rigid lens over the central cornea and may also reduce corneal oxygenation. This
      aim of this study was to estimate the equivalent oxygen percentage beneath such
      lenses and to review the clinical records of users to determine their success
      rate. METHODS: The right eyes of four normal subjects were covered for 5 minutes
      with a combination of rigid gas permeable (Boston ES or 7 [Polymer Technology
      Corp., Rochester, NY]) and soft (Acuvue [Johnson & Johnson, Jacksonville, FL],
      Keraflex [KF] 3 or 5 [Blanchard, Sherbrooke, QC, Canada]) contact lenses. After
      removal of the lenses, oxygen tension was measured with a Clark electrode. In
      order to determine whether measurements of oxygen tension were supported by
      clinical data, the clinical files of 11 patients fitted with KF 5-Boston ES
      piggyback lenses were reviewed for the presence of corneal edema. RESULTS: Mean
      relative equivalent oxygen percentage ranged from 6.9% to 11.2% beneath the
      following lens combinations: KF 3-Boston ES; KF 3-Boston 7; KF 5-Boston ES; KF 5
      Boston 7; Acuvue-Boston ES; and Acuvue-Boston 7. Of the ten patients followed
      after dispensing, none had any sign of corneal edema. Nine had worn their contact
      lenses for periods up to 6 years. CONCLUSIONS: Based on the measured equivalent
      oxygen percentage and on the absence of corneal edema in patients, the
      combination of countersunk KF 5 with Boston ES lenses provides enough oxygen to
      fulfill corneal needs in oxygen during daily wear.

PMID- 11506438
TI  - Effects of low and hyper Dk rigid gas permeable contact lenses on Bcl-2
      expression and apoptosis in the rabbit corneal epithelium.
AB  - PURPOSE: To study Bcl-2 expression and apoptotic cell shedding of the rabbit
      corneal epithelium during extended wear of low and hyper Dk rigid gas permeable
      (RGP) contact lenses. METHODS: Rabbits were fit with either a low or a hyper Dk
      RGP lens (Dk/Ltotal= 10 and 97). The rabbits wore the lenses for either 24 hours,
      3 days, or 1 week at which point they were humanely sacrificed.
      Immunocytochemistry and western blot analyses were performed to detect Bcl-2 in
      the corneal epithelium; TUNEL assay (TdT-mediated dUTP nick-end labeling) was
      used to identify apoptotic epithelial cells. RESULTS: 1) Immunocytochemistry: In
      the normal cornea, antibodies to Bcl-2 uniformly stained nuclei of all epithelial
      cell layers. Occasional surface epithelial cells, however, showed no anti-Bcl-2
      nuclear staining; concomitant TUNEL assay revealed that all TUNEL-labeled-surface
      cells were Bcl-2 negative. By contrast, RGP contact lens wear, regardless of test
      lens oxygen transmissibility or lens wearing interval, significantly decreased
      both the total number of Bcl-2 negative and TUNEL-labeled cells on the epithelial
      surface (P < 0.05). In addition, contact lens wear was associated with labeling
      of keratocytes with TUNEL assay in the anterior stroma. 2) Western blot analysis:
      Total epithelial layer Bcl-2 expression was markedly decreased in the low Dk lens
      test group but was similar to control values in the hyper Dk lens test group.
      CONCLUSION: Bcl-2 protein seems to play an important role in the regulation of
      apoptotic cell shedding in the normal rabbit corneal epithelium. The identical
      staining pattern was seen in previous studies of the normal human cornea. RGP
      contact lens wear, however, appears to block the changes in Bcl-2 protein prior
      to apoptotic surface cell shedding, suggesting a lens-related anti-apoptotic
      effect. Taken together, these findings may explain why contact lens wear reduces
      surface cell exfoliation as previously reported in human studies.

PMID- 11506440
TI  - Tolerance to different kinds of contact lenses in young atopic and non-atopic
      wearers.
AB  - PURPOSE: To study tolerance to three types of soft and onetype of rigid gas
      permeable (RGP) contact lens in young atopic and non-atopic subjects starting to
      wear contact lenses. METHODS: A prospective study was conducted in 73 young
      subjects (mean age: 18.7 years, range: 11-37 years). Each subject was allotted at
      random to one of four groups. Each group of subjects used a different type of
      contact lens for a year. Tolerance was determined by means of self-assessment by
      the subjects, ophthalmologic methods, and cytology. The study was conducted on a
      blind basis. The investigators assessing tolerance did not know what kind of lens
      a patient had been wearing. RESULTS: Fifty-six percent of subjects who had used
      soft contact lenses, but only 14% of RGP lens users described their lenses as
      very comfortable to wear. Sixty-three percent of non-atopic subjects but only 47%
      of atopic subjects described their lenses as very comfortable to wear. No
      differences were found between the three types of soft contact lens. Four cases
      of giant papillary conjunctivitis (GPC) and two cases of macropapillary reaction
      were recorded. No connections with atopy, type of lens, or lens care solution
      were found. CONCLUSIONS: Higher percentages of users of soft contact lenses than
      users of RGP contact lenses described their lenses as very comfortable to wear.
      Wearing of all types of lenses was associated with follicular or papillary
      reactions in some subjects. Young people can wear contact lenses safely only if
      monitoring takes place at least twice a year.

PMID- 11506441
TI  - Detachment of trophozoites of Acanthamoeba species from soft contact lenses with
      BEN22 detergent, BioSoak, and Renu multi-purpose solutions.
AB  - PURPOSE: BEN22 detergent was studied for its ability to detach Acanthamoeba from
      soft contact lenses without mechanical cleaning or separate cleaning agents.
      METHODS: Trophozoites of Acanthamoeba castellanii and A. polyphaga were adhered
      onto nonionic, high water content soft contact lenses. The lenses were immersed
      for 2 hours in contact lens care solutions and the remaining trophozoites were
      counted microscopically. The counts were compared to the counts on the same lens
      before treatment. RESULTS: BEN22 (50:50 mixture of L-alpha-L-rhamnopyranosyl-beta
      hydroxydecanoyl-beta-hydroxydecanoate and 2-O-alpha-L-rhamnopyranosyl-alpha-L
      rhamnopyranosyl-beta-hydroxydecanoyl-beta-hydroxydecanoate) (Kassell Industries,
      Inc., Wisconsin Dells, WI) in a concentration of 0.05% detached the trophozoites
      to a statistically significant greater extent than saline, but commercial ReNu
      Multi-Purpose Solution (Bausch & Lomb, Italy) and BioSoak (Finnsusp Ltd.,
      Finland) did so as well. ReNu Multi-Purpose Solution was more effective than
      0.005% BEN22 in detaching the trophozoites of both of the Acanthamoeba strains.
      After the 2 hour immersion period, a maximum of 97% of the initial trophozoites
      were detached. The variation between individual lenses was significantly greater
      than that within the different areas of one lens. CONCLUSIONS: BEN22 had no
      reliable detaching effect on Acanthamoeba. The variation between lenses was
      great, and the rate of detachment was low with all the agents tested indicating
      that immersion and rinsing in the solutions tested cannot be considered as a safe
      substitute for proper disinfection against Acanthamoeba in contact lens care.

PMID- 11506442
TI  - Competitive adsorption of proteins on hydrogel contact lenses.
AB  - PURPOSE: To compare sequential and competitive adsorption of some proteins onto
      hydrogel contact lenses. METHODS: New, never-worn, group IV soft contact lenses
      were incubated in freshly prepared solutions of lysozyme, alpha-lactalbumin, and
      ribonuclease at room temperature for 5 days with constant shaking, during which
      time their adsorbed protein was directly measured using UV absorbances at 280 nm.
      Adsorption isotherms were prepared. The lenses were rinsed with distilled water
      following a second protein treatment. RESULTS: We found that the chemical
      composition of the lens and the charge of the previously adsorbed protein
      affected sequential and competitive adsorption of proteins on a contact lens
      surface. CONCLUSIONS: Sequential adsorption occurs only if the second protein has
      a more favorable electrostatic interaction; sequential adsorption involves almost
      total displacement of the preadsorbed protein.

PMID- 11506443
TI  - Visual performance of rigid gas permeable contact lenses in patients with corneal
      opacity.
AB  - PURPOSE: To evaluate the visual performance of rigid gas permeable (RGP) contact
      lenses in patients with nebular and nebulo-macular corneal opacity and correlate
      the improvement in visual acuity with other visual parameters. METHODS: In a
      prospective study, visual performance of RGP contact lenses was evaluated in eyes
      with corneal opacity involving the pupillary area. The baseline visual acuity and
      other visual parameters with glasses were compared with those recorded with RGP
      contact lenses. The visual functions evaluated were visual acuity, contrast
      sensitivity, glare acuity, and mesopic vision. Binocular status with RGP contact
      lenses was assessed. All patients were followed up for 3 months. RESULTS: Twenty
      eight eyes (26 patients) with nebular or nebulo-macular corneal opacity were
      included in this study. All eyes (100%) achieved significantly better visual
      performance with RGP contact lenses than with glasses (P< 0.0020). Visual acuity
      of 6/9 or better was achieved in 50% of patients with RGP contact lenses compared
      to none with glasses. RGP contact lenses improved the visual acuity by 0.27
      decimals over the baseline value with glasses, butthe improvement for mesopic
      vision and glare acuity was significantly lower at 0.15 and 0.06 decimals
      respectively. Similarly, contrast sensitivity did not improve to the same extent
      as visual acuity. Stereopsis was present only in patients with best corrected
      visual acuity of 6/9 or better with RGP lenses. CONCLUSION: RGP contact lenses
      improved the visual acuity and other visual performance in patients with reduced
      vision due to nebular or nebulo-macular corneal opacity. However, contrast
      sensitivity, glare acuity, and mesopic vision did not improve to the same extent
      as visual acuity.

PMID- 11506444
TI  - Fungal ring infiltrates in disposable contact lens wearers.
AB  - PURPOSE: To report two cases of ring infiltrates in disposable contact lens
      wearers resembling Acanthamoeba keratitis but later identified as fungus.
      METHODS: We report two patients with histories of disposable soft contact lens
      use, who, on initial presentation, were found to have corneal ring infiltrates
      and were treated for presumed Acanthamoeba keratitis. Microbiological studies,
      which included Gram stain and Gomori methenamine silver stain, as well as blood
      agar, chocolate agar, thioglycolate broth, Sabouraud agar, nonnutrient agar with
      Escherichia coli overlay, and Lowenstein-Jensen plates, were performed. RESULTS:
      Microbiological studies revealed fungi in both cases. CONCLUSIONS: Fungal
      keratitis is an uncommon complication of disposable soft contact lens use, but it
      should be considered in the differential diagnosis of corneal ring infiltrates.

PMID- 11506445
TI  - Introduction and commentary: developmental perspectives on violence and
      victimization.

PMID- 11506446
TI  - Childhood risk factors for persistence of violence in the transition to
      adulthood: a social development perspective.
AB  - This study examined violent behavior from ages 13 to 21 and identified predictors
      at age 10. Logistic regression was used to assess predictors of developmental
      patterns of violence. The sample is from a study of 808 youth interviewed
      annually from age 10 to 16 years, and again at ages 18 and 21. Over 28% of the
      youth in the sample reported nonviolence throughout adolescence and into early
      adulthood. Most youth (55%) engaged in violence in adolescence but desisted from
      violence in early adulthood, while 16% persisted in violent behavior at age 21.
      Violence in adolescence was best predicted by male gender, Asian American
      ethnicity (a protective factor), childhood fighting, early individual
      characteristics, and early antisocial influences. Adult persistence of violence
      was best predicted by male gender, early school achievement (which was
      protective), and early antisocial influences. Early prosocial development was
      also protective against violence persistence for females. Implications for
      prevention are discussed.

PMID- 11506447
TI  - Correlates contributing to involvement in violent behaviors among young adults.
AB  - The study examines the extent to which gender, personality attributes, household,
      community, and environmental factors are associated with violent behaviors in
      young adulthood. The authors present findings from a sample of 765 21-year-old
      individuals participating in a drug and delinquency prevention study. Personality
      attributes, opportunities, and social acceptability of antisocial behaviors were
      identified as accounting for gender differences and having more influence on
      violent behavior than environmental correlates. Implications for preventive
      intervention are discussed.

PMID- 11506448
TI  - Gun violence exposure and trauma among rural youth.
AB  - This study compared rural youth exposed to gun violence and rural youth not
      exposed to gun violence on a number of variables: anger, anxiety, dissociation,
      depression, posttraumatic stress, total trauma, violent behavior, parental
      monitoring, and levels of violence in the home, school, and community. One-fourth
      (25%) of the rural youth in this study reported having been exposed to gun
      violence at least once. Youth exposed to gun violence reported significantly more
      anger, dissociation, posttraumatic stress, and total trauma. In addition, youth
      exposed to the violence of guns reported significantly higher levels of violent
      behaviors and exposure to violence in other settings and also reported lower
      levels of parental monitoring. The present study contributes to the growing body
      of literature addressing the stereotype that rural communities are not immune to
      the violence of firearms. This stereotype acts as a barrier to mental health
      practice, research, and policy issues in rural communities.

PMID- 11506449
TI  - Characteristics of homicidal and violent juveniles.
AB  - Homicidal youth have received considerable attention in the mass media and social
      science literature in recent years. Due to several methodological obstacles,
      relatively little is known about the premorbid and offense characteristics of
      this population. The current investigation compared 30 juvenile males charged
      with murder with a group of 62 juvenile males charged with other violent felony
      offenses. Comparisons were made across 33 demographic, historical, clinical,
      offense, and forensic characteristics. Both groups were similar in their
      demographic characterishics and family backgrounds. Juvenile homicide defendants,
      however, were less likely than the comparison group to have a current Axis I
      psychiatric diagnosis. Homicide defendants were also more likely to have acted
      alone and to have committed their alleged crime in a domestic setting.
      Implications of the results are discussed as are suggestions for future research.

PMID- 11506450
TI  - Short-term stability and prospective correlates of bullying in middle-school
      students: an examination of potential demographic, psychosocial, and
      environmental influences.
AB  - Stability and change of bullying over a four-month interval was examined in 516
      middle school students (grades 6-8). The stability coefficient was .65 for the
      entire sample. There was a significant increase in bullying behavior from Time 1
      to Time 2 for 6th grade students; no significant change in bullying was found
      among 7th or 8th graders. For 6th graders, a greater confidence in using non
      violent strategies was associated with less bullying at Time 2, while beliefs
      supportive of violence and misconduct, less positive adult influences, and more
      negative peer influences were associated with greater likelihood of bullying at
      Time 2. Higher levels of impulsivity, anger, and depression were also associated
      with greater levels of bullying over time. Several explanations for the increase
      in bullying behaviors among 6th graders are discussed and linked to intervention
      efforts.

PMID- 11506451
TI  - Moral commitment and the effects of social influences on violent delinquency.
AB  - The present article investigates the issue of whether and how moral commitment
      regarding violence conditions the relationship between a set of social
      environmental variables and violent delinquency. Three mutually exclusive
      hypotheses were evaluated using data from the National Youth Survey. The first,
      emanating from a purely environmental perspective, holds that moral commitment to
      non-violence does not condition the relationships of social variables to violent
      delinquency. The second hypothesis predicts that social factors have their
      greatest effect on violent behavior among those most strongly opposed to
      violence. The third hypothesis anticipates that social variables have their
      greatest impact on violent delinquency among those with violent attitudes. The
      results yielded strong support for the third hypothesis. Theoretical implications
      are discussed.

PMID- 11506452
TI  - The effects of a high-risk environment on the sexual victimization of homeless
      and runaway youth.
AB  - Based on the structural-choice theory of victimization, the current study
      examines the effects of a high-risk environment on the sexual victimization of
      311 homeless and runaway youth. Results from logistic regression revealed that
      survival sex, gender, and physical appearance were significantly associated with
      sexual victimization. Results from a series of interactions also revealed that
      the effects of deviant behaviors on sexual victimization varied by gender and
      age. Although males and females engaged in similar activities, young women were
      more likely to be victims of sexual assault. These findings suggest that engaging
      in high-risk behaviors predispose some people to greater risks but it is the
      combination of these behaviors with gender and/or age that determines who will
      become victimized.

PMID- 11506453
TI  - The gender cycle of violence: comparing the effects of child abuse and neglect on
      criminal offending for males and females.
AB  - Despite ample evidence of the relationship between childhood maltreatment and
      offending, the ways in which the cycle of violence operates remain unclear. For
      example, feminist researchers contend that female victims are more likely to
      become offenders, compared to male victims, but more research is needed to
      substantiate this claim. Moreover, the contradictions in research findings-with
      retrospective research demonstrating that most offenders have histories of abuse,
      and prospective work indicating that the majority of victims do not become
      involved in crime-highlight the importance of identifying the intermediating
      variables that lead from maltreatment to criminality. This review summarizes
      investigations related to the cycle of violence, discusses the intermediating
      circumstances that may affect the cycle, and identifies whether or not these
      processes are similar for women and men.

PMID- 11506454
TI  - Peroxisome proliferators: their biological and toxicological effects.
AB  - One of the most rapidly developing areas of organelle biology, which has a major
      involvement in biochemical pharmacology, is the research into the peroxisomal
      function. There is a large group of compounds that are capable of inducing liver
      enlargement, proliferation of peroxisomal structures, and induction of
      peroxisomal and extraperoxisomal fatty acid-oxidizing enzymes in rodent liver,
      called peroxisome proliferators. This list includes hypolipidemic drugs,
      analgesics, uricosuric drugs, environmental pollutants, phthalates, etc. Some
      peroxisome proliferators have also been shown to increase the incidence of liver
      tumors. This review describes the characteristics of peroxisome proliferation in
      rodent liver and gives examples of different classes of chemicals that produce
      this effect. Mechanisms of initiation of peroxisome proliferation in rodent
      hepatocytes, including peroxisome proliferator-activated receptors, are also
      described. Rodent peroxisome proliferators are not considered to be genotoxic
      agents. Proposed mechanisms of liver tumor formation include induction of
      sustained oxidative stress, enhanced cell replication, promotion of spontaneous
      preneoplastic lesions, and inhibition of apoptosis. In addition, the absence of
      effects of peroxisome proliferators on peroxisome proliferator-associated
      parameters supports the hypothesis that human liver cells are refractory to
      peroxisome proliferator-induced hepatic carcinogenesis.

PMID- 11506455
TI  - Medical biochemistry in Macedonia: a profession for physicians and natural
      scientists.
AB  - Medical biochemistry or clinical chemistry in its roots is an interdisciplinary
      science between natural sciences and medicine. The largest part of medical
      biochemistry is natural science (chemistry, biochemistry, biology, physics,
      mathematics), which is very well integrated in deduction of medical problems.
      Medical biochemistry throughout the world, including Macedonia, should be a
      professional field open to both physicians and natural scientists, according to
      its historical development, theoretical characteristics and applied practice.
      Physicians and natural scientists follow the same route in clinical chemistry
      during the postgraduate training of specialization in medical
      biochemistry/clinical chemistry. However, in Macedonia the specialization in
      medical biochemistry/clinical chemistry is today regulated by law only for
      physicians and pharmacists. The study of clinical chemistry in Europe has shown
      its interdisciplinary character. In most European countries different
      professions, such as physicians, chemists/biochemists, pharmacists, biologists
      and others could specialize in clinical chemistry. The question for the next
      generation of specialists in Macedonia is whether to accept the present
      conditions or to attempt to change the law to include chemists/biochemists and
      biologists as well. The latter used to be a practice in Macedonia 20 years ago,
      and still is in many European countries. Such change in law would also result in
      changes in the postgraduate educational program in medical biochemistry in
      Macedonia. The new postgraduate program has to follow the European Syllabus,
      recommended by EC4. To obtain sufficient knowledge in clinical chemistry, the
      duration of vocational training (undergraduate and postgraduate) for all trainees
      (physicians, pharmaceutics, chemists/biochemists and biologists) should be 8
      years.

PMID- 11506456
TI  - Stress tolerance test and SDS-PAGE for the analysis of urinary proteins in
      children and youths.
AB  - Excretion of urinary proteins (UP) is an important marker for the evaluation of
      patients with progressive renal disease. In order to analyze quantitative and
      qualitative variability of UP in relation to physical activity, we used
      standardized stress tolerance test and SDS-PAGE. Five urine samples were obtained
      from each patient at rest, during ordinary daily activity and after physical
      stress. Determination of total proteins was performed using Meulman's classic
      method with sulfosalicylic acid. UP were separated by ultrathin horizontal
      gradient SDS-PAGE according to Gorg. There were 142 patients; 40 with
      poststreptococcal glomerulonephritis (PSGN), 11 with diabetes mellitus, 16 with
      chronic pyelonephritis and 75 who attended for investigation of asymptomatic
      proteinuria. Functional proteinuria was established in 42 subjects, who displayed
      maximal UP excretion during stress and the presence of apolipoprotein AI on SDS
      PAGE. Children with PSGN showed no significant increase of UP during stress. Some
      children with diabetes mellitus (27%) and chronic pyelonephritis (47%) displayed
      microproteinuria or overt proteinuria after stress. Quantitative and qualitative
      changes in total UP excretion can be detected by stress tolerance test and SDS
      PAGE. It remains to be seen whether stress tolerance test can identify children
      and youths who are at higher risk for disease progression.

PMID- 11506457
TI  - Atherosclerosis risk factors related to hemodialysis duration and erythropoietin
      therapy.
AB  - Patients undergoing hemodialysis are at risk for atherosclerosis and its
      complications. The aim of this study was to examine the effect of erythropoietin
      therapy and hemodialysis duration on some of the atherosclerotis risk factors.
      The patients were divided into four groups: I: patients undergoing hemodialysis
      for less than 10 years (n=22); II: patients undergoing hemodialysis for more than
      10 years (n=17); III: patients on no erythropoietin (n=21); IV: patients on
      erythropoeitin therapy (n=18). A control group of 20 subjects was also examined.
      Triglycerides, total cholesterol, low-density lipoprotein and high-density
      lipoprotein, lipoprotein(a), apolipoprotein-A1, apolipoprotein-B and lipid
      peroxidation were examined. There was a significant increase in triglycerides, to
      2.59+/-1.2 mmol/l (p<0.001) and in lipid peroxidation in hemodialysis patients,
      to 5.02+/-0.9 micromol/l vs. controls (p<0.001). Significantly elevated
      triglycerides and lipid peroxidation levels were found in the patients with
      longer hemodialysis duration. Triglycerides were elevated in group II vs. group
      I, to 2.90+/-1.0 mmol/l. (p<0.05). Lipid peroxidation in group II, 5.40+/-1.0
      micromol/l, showed significant difference compared to group I (p<0.05).
      Erythropoietin treatment did not affect any of the examined parameters. These
      results indicate increased risk for atherosclerosis related to hemodialysis
      duration. Besides the renal disease itself, hemodialysis may also be one of the
      risk factors for atherosclerosis.

PMID- 11506458
TI  - Maternal serum screening for Down's syndrome, open neural tube defects and
      trisomy 18.
AB  - Maternal serum screening identifies women at an increased risk of a pregnancy
      with Down's syndrome or trisomy 18 or an open neural tube defect. The triple
      test, consisting of maternal serum alpha-fetoprotein, unconjugated estriol and
      human chorionic gonadotropin was carried out by a chemiluminescence immunoassay
      method in our laboratory. The study consisted of 373 pregnant women. The
      gestational range for the study group was 14-22 weeks. The mean maternal age for
      the study group was 28.53 +/- 5.46 years (range 17.4 to 43.5 years); 9.1% of the
      women were considered at high risk for Down's syndrome based on the test results.
      In our study the detection rate for Down's syndrome by prenatal karyotyping was
      66.6%. Maternal serum screening allows reduction of the number of women requiring
      amniocentesis without a significant decrease in the detection rate.

PMID- 11506459
TI  - The effect of Escherichia coli-derived lipopolysaccharides on plasma levels of
      malondialdehyde and 3-nitrotyrosine.
AB  - The aim of this study was to determine the effect of Escherichia coli (E. coli)
      derived lipopolysaccharide on rat plasma low density lipoprotein (LDL),
      malondialdehyde and 3-nitrotyrosine levels (an indicator of protein nitration).
      Six hours after intraperitoneal administration of E.coli, plasma LDL was measured
      electrophoretically and malondialdehyde level was measured by spectrophotometric
      method. Plasma malondialdehyde was significantly (p<0.001) elevated in E. coli
      injected rats (4.97 +/- 1.33; n=10) in comparison to control animals (1.83 +/-
      0.5; n=10). In addition, plasma 3-nitrotyrosine level, determined by reverse
      phase HPLC, was also increased in the infected group (2.84 +/- 1.17 to 0.22 +/-
      0.13; n=10). This increase was statistically significant (p<0.001). An increased
      level of oxidation of lipids and 3-nitrotyrosine was observed as a result of free
      radical-mediated damage in plasma. In conclusion, asymptomatic infections may
      increase the risk of atherosclerosis by inducing free radical formation and a
      consequent increase in the oxidation of LDL.

PMID- 11506460
TI  - Isolation of fetal cells from the maternal circulation: prospects for the non
      invasive prenatal diagnosis.
AB  - The research into non-invasive and invasive prenatal diagnostic techniques
      developed almost in parallel. On the one hand the need was arising to ensure the
      birth of normal progeny in all cases, while on the other, it was not possible to
      eliminate the abortion risks connected with the invasiveness of amniocentesis
      (risk of abortion 1/200), chorion villi sampling, (risk of abortion 2%) and
      funicolocentesis (risk of abortion 3-4%). One of the first researchers in the non
      invasive field was Adinolfi who published the earliest data in 1974 on the
      possibility of detecting three types of fetal cells in the maternal circulation
      using flow cytometry. Adinolfi suggested the possibility of using fetal cells
      present in the maternal circulation for prenatal diagnosis of chromosome or
      biochemical anomalies. Our review takes into consideration the latest
      methodological and technical progress in relation to the study of fetal cells in
      maternal circulation, without considering cells present in the endocervical canal
      where from the 8th week of pregnancy it is only possible to obtain trophoblast
      cells. This technique has since been abandoned due to the scarcity of cellular
      material available, the greater risk of contamination by cells of maternal
      origin, and also because the recovery of the cells is unpredictable, despite
      their potential use for the early non-invasive diagnosis of sex. The following
      issues are addressed in this review: the characterization of the fetal cell types
      present in the maternal circulation, the methods of their separation and
      enrichment, and the methods of genetic diagnostics applied.

PMID- 11506462
TI  - A novel missense mutation C127R (FH Zagreb) in the LDL-receptor gene.
AB  - We employed the analysis of single-strand conformation polymorphisms to identify
      mutations in exon 4 of the low density lipoprotein receptor gene causing familial
      hypercholesterolemia. Three familial hypercholesterolemia heterozygotes had
      abnormal single-strand conformation polymorphism patterns. DNA sequencing
      revealed that the abnormal pattern of exon 4A was due to heterozygosity (T/C) at
      nucleotide 442. Nucleotide 442 is the first base of codon 127, and the T-->C
      mutation (C127R) changes this codon from CysTGT to ArgCGT. Abnormal patterns of
      exon 4B were due to heterozygosity (A/G) at nucleotide 662: nucleotide 662 is the
      second base of codon 200, and the A-->G mutation (D200G) changes this codon from
      AspGAC to GlyGGC. Mutation D200G was previously described as FH Padova, but
      mutation C127R (FH Zagreb) has not been reported previously. This novel mutation
      was confirmed by restriction endonuclease analysis with Dsa I. The screening of
      420 familial hypercholesterolemia heterozygotes suggests that C127R and D200G
      account for about 0.7% of mutations causing familial hypercholesterolemia in
      Croatia.

PMID- 11506461
TI  - Melting temperature analysis as quantitative method for detection of point
      mutations.
AB  - Different methods have been devised to detect point mutations. Some are very
      sensitive, detecting mutations even in a background of normal tissue, but none
      provide information about the percentage of cells with mutant DNA. Here we
      describe an easy, fast and reliable method, melting temperature analysis, which
      not only detects point mutations but also provides quantitative information on
      the percentage of cells with mutant DNA. By this method we detected a G-A
      transition in codon 12 of the K-ras gene in DNA of subjects with colorectal
      cancer. The K-ras mutation was found in 9/10 bowel cancers and 8/10 normal
      adjacent samples. It was also detected in 4/7 stool samples from the same
      patients. In colorectal cancers, the proportion of K-ras mutant cells was
      variable: in two the mutant/wild-type DNA ratio was 30/70, in three 50/50, and in
      four 70/30. Melting temperature analysis was sensitive for the detection of point
      mutations in bowel cancer and also in apparently normal tissue, providing
      quantitative information about the percentage of cells with mutant DNA.

PMID- 11506463
TI  - Plasma endothelin-1 and big endothelin-1 levels in superior and inferior vena
      cava during protracted antiorthostatic hypokinetic/hypodynamia in rats.
AB  - The plasma levels of endothelin-1 and big endothelin-1 were evaluated in blood of
      rats in the superior and inferior vena cava, in normal posture (synchronous
      controls), and after 12 days head-down suspension and 1 day recovery in normal
      posture. In synchronous controls, the mean plasma concentration of endothelin-1
      in inferior vena cava or superior vena cava was almost the same (5.89+/-0.63
      pmol/l and 5.67+/-0.64 pmol/l, respectively), whereas the mean plasma
      concentration of big endothelin-1 was higher (p<0.05) in superior vena cava
      compared to inferior vena cava (5.49+/-0.75 pmol/l and 1.39+/-0.15 pmol/l,
      respectively). In samples from superior vena cava of head-down suspended rats big
      endothelin-1 levels were significantly lower (p<0.05) up to day 9 of suspension,
      compared to non-suspended synchronous controls, whereas endothelin-1 values were
      higher (p<0.05). Big endothelin-1 concentration was higher (p<0.05) in inferior
      vena cava compared to non-suspended synchronous controls. The behaviour of
      endothelin-1 was more complex, endothelin-1 levels were lower (p<0.05) on day 1
      of head-down suspension and higher (p<0.05) in samples taken on days 9 and 12.
      After 1 day recovery endothelin-1 and big endothelin-1 concentrations returned to
      normal in both superior vena cava and inferior vena cava. These data indicate
      that the endothelial system involvement for the two venous beds is different and
      suggest that local rather than systemic evaluation could better explain
      endothelial involvement and the contribution of different anatomic sites to the
      biosynthesis, conversion and clearance of the various involved molecules.

PMID- 11506464
TI  - Sensitive chemiluminescence immunoassay for the determination of rat serum alpha1
      acid glycoprotein.
AB  - We present the establishment of a sensitive immunoassay for the determination of
      alpha1-acid glycoprotein (orosomucoid, AGP) in rat serum. The assay is based upon
      antigen capture by surface-immobilized specific polyclonal rabbit anti-AGP
      antibodies with biotinylated rat AGP (rAGP) as the tracer, and formatted as
      competitive enzyme immunoassay. Signaling is performed by streptavidin-conjugated
      horseradish peroxidase. Enzyme activity is quantified by an enhanced
      chemiluminometric method, allowing the sensitive detection of rAGP serum levels
      in small sample volumes.

PMID- 11506465
TI  - Increased serum and salivary immunoglobulins against Candida albicans in HIV
      infected patients with oral candidiasis.
AB  - The aim of this study was to explore anti-Candida albicans systemic and mucosal
      humoral responses against Candida virulence antigens such as somatic antigen and
      secreted aspartic proteases (Saps) in HIV-infected patients with oral
      candidiasis. Twenty-eight subjects were included in the study: 11 HIV-positive
      patients without oral candidiasis (group A), 6 HIV-positive patients with oral
      candidiasis (group B) and 11 HIV-negative healthy controls (group C). Total IgA,
      IgG and IgM concentrations and antibodies to C. albicans (somatic antigen, Sap1,
      Sap6) were measured in serum and saliva. We developed a time-resolved
      immunofluorometric assay with biotin and europium-labeled streptavidin for this
      purpose. Salivary total IgA, IgG and IgM concentrations were higher in group B.
      IgA, IgG and IgM anti-C. albicans antibodies (against somatic antigen, Sap1,
      Sap6) were higher in saliva and serum from patients from group B compared with
      patients from group A and controls. Our results suggest that, in oral
      candidiasis, HIV-infected patients have a high mucosal response, specifically
      directed against C. albicans virulence antigens, such as somatic antigen, Sap1
      and Sap6.

PMID- 11506466
TI  - Elevated carbohydrate antigen 19-9 (CA 19-9) in patients with Echinococcus
      infection.
AB  - The carbohydrate antigen 19-9 (CA 19-9), a determinant (sialylated lacto-N
      fucopentaose 119) of a circulating oligosaccharide antigen, is a frequently used
      tumor marker. Echinococcus spp. infects humans throughout the world and may be
      able to synthesize closely related molecules which could interfere with the
      measurement and interpretation of CA 19-9 concentration. The main objective of
      the present study was to determine the range of CA 19-9 levels in the sera of
      patients infected by E. granulosus (cystic hydatide disease; CYSHD) or E.
      multilocularis (alveolar hydatide disease; ALVHD). Serum samples were collected
      from patients (aged 10-85 years) over a period of 5 years: from 19 patients with
      CYSHD and from 20 patients with ALVHD. Infection was confirmed by positive
      Echinococcus serology and clinical evidence provided by imaging and/or
      histopathological findings. CA 19-9 was detectable in 13 patients with CYSHD
      (13.5 +/- 8.5 kU/l) and 13 patients with ALVHD (30.0 +/- 21 kU/l; p < 0.05). Thus
      ALVHD patients exhibited a significantly higher plasma level of CA 19-9 than
      CYSHD patients. The serum level of CA 19-9 assessed with an increased cut-off
      value (> 22 kU/l) was elevated in nine (45%) of 20 ALVHD patients compared to two
      (11%) of 19 CYSHD patients (p < 0.05). Sera from patients with Echinococcus
      multilocularis infection contain substances which cross-react with CA 19-9. These
      substances originate either from the parasite or are synthesized by the host in
      response to the infection, and possibly bear the Lewis-a antigen or closely
      related structures which are recognized by anti-CA 19-9 antibodies. Our findings
      are relevant to the investigation of patients presenting with cystic lesions for
      which the differential diagnosis includes an infectious or neoplastic origin.

PMID- 11506467
TI  - Interpretation of sequential measurements of cancer antigen 125 (CA 125),
      carcinoembryonic antigen (CEA), and tissue polypeptide antigen (TPA) based on
      analytical imprecision and biological variation in the monitoring of ovarian
      cancer.
AB  - The main objective with cancer antigen 125 (CA 125), carcinoembryonic antigen
      (CEA), and tissue polypeptide antigen (TPA) monitoring of ovarian cancer patients
      is to detect an early change of disease activity with high reliability. We
      hypothesized that a monitoring scheme for ovarian cancer patients with
      serological tumor markers should take into account the stochastic variation, i.e.
      the probability that observed increases and decreases may solely be due to
      analytical imprecision and normal intra-individual biological variation. The aim
      of this study was to provide a detailed characteristic of the within-subject mean
      steady state concentrations and the associated variability in healthy individuals
      with an age distribution representative for ovarian cancer patients. Thirty-one
      healthy women with a median age of 55 years comprised the study population.
      Sixteen blood samples were collected from each subject in four series, with four
      samples per series, over a period of approximately 1 year. We found that, i)
      natural logarithmic-transformed concentrations were more homogeneously
      distributed between individuals than the original concentrations, ii) the within
      subject mean steady state levels, the standard deviations, and the coefficients
      of variation differed among subjects, and iii) the steady state variability
      differed among the markers. In conclusion, our data indicate that the assessment
      of sequential CA 125, CEA, and TPA concentrations is more complex than hitherto
      recognized. We suggest that it is necessary to adjust the assessment criteria to
      the type of marker, and that assessment may be facilitated if based on natural
      logarithmic transformed concentrations.

PMID- 11506469
TI  - Educational letter.

PMID- 11506468
TI  - Inter-laboratory evaluation of the COBAS INTEGRA 400 analytical system.
AB  - COBAS INTEGRA 400 is a random-access analytical system consolidating assays for
      clinical chemistry analytes, electrolytes, serum proteins, drugs of abuse and
      therapeutic drugs. Analytical performance and practicability of the instrument
      were evaluated in seven laboratories over a 2-year period in parallel with system
      development. Good within-run and total imprecision for all assays was observed
      with a few exceptions for specimen pools with low concentration or activity. The
      coefficients of variation for total imprecision were well below 3.0% for clinical
      chemistry analytes and electrolytes, and below 5.0% for serum proteins and
      therapeutic drugs. Method comparisons demonstrated a good agreement with the
      various systems used for comparison, with slopes varying typically from 0.94 to
      1.05, and Spearman correlation coefficient generally > 0.975. Accuracy was
      verified by recovery of controls and certified reference materials within 90 to
      110% of target values. Assay ranges were linear within +/- 5%. No carry-over on
      reagent or sample pipetting systems was observed. Manufacturer-specified
      interference limits and onboard stabilities of reagents were confirmed. A time
      study for calculating direct personnel times and total processing time was
      carried out in three laboratories under different conditions including
      consolidated, STAT and dedicated use. On a scenario-independent basis, the total
      working time was shorter on the COBAS INTEGRA 400 than on routine systems in all
      three laboratories. Personnel time, in particular, was significantly reduced when
      compared to routine instruments. In general, system practicability was judged
      very positively in all laboratories. Owing to its versatility, the instrument is
      best placed as a consolidated workstation in small- to medium-sized laboratories
      or as an instrument for special determinations such as serum proteins, drugs,
      urinalysis or emergency analyses in large laboratories.

PMID- 11506470
TI  - Protein G ELISA for the detection of circulating immune complexes. An alternative
      to the solid-phase radioimmunoassay for the monoclonal rheumatoid factor.

PMID- 11506471
TI  - Human herpesvirus 6 in the pathogenesis of multiple sclerosis.
AB  - Multiple sclerosis (MS) is one of the most common disabling neurological diseases
      affecting young adults. It is a chronic disease characterised by inflammation and
      demyelination. The aetiology of MS is still unknown, but involvement of viruses
      has been suspected for many years. Recently much interest has focused on human
      herpesvirus 6 (HHV-6), since the virus has been detected in MS plaques in the
      brain and patients with MS have been shown to have an aberrant immune response to
      HHV-6. Results from different studies are, however, conflicting and in the light
      of the long list of previous claims to have found the viral aetiology of MS it is
      necessary to interpret the HHV-6 findings with great caution. Possible mechanisms
      for virally induced demyelination and autoimmunity are discussed in this review,
      and the evidence for and against a role for HHV-6 in MS is summarised.

PMID- 11506472
TI  - Aerogenous infection of microbiologically defined minipigs with Streptococcus
      suis serotype 2. A new model.
AB  - Streptococcus suis serotype 2 is the cause of serious infections in animals and
      humans, but certain aspects of the infection pathogenesis still remain unclear.
      In this study an experimental model of aerogenous infection and induction of
      septicemia with S. suis serotype 2 was established in microbiologically defined
      Gottingen minipigs. Ten animals were exposed to aerosolized S. suis after
      previous exposure to mild acetic acid in aerosol. Six of the animals were
      immunosuppressed with prednisolone acetate on different days. All the animals
      were monitored clinically until euthanasia on days 6 to 13 after exposure.
      Necropsy was performed and samples were taken for microbiology, histopathology,
      and immunohistochemistry Three out of four animals immunosuppressed on days 5 to
      7 after exposure developed S. suis septicemia, and S. suis could be detected in
      the tonsil of the soft palate and/or the nasal cavity of all exposed animals.
      Thus, using the presented model, local as well as systemic infection with S. suis
      serotype 2 was established in the Gottingen minipig. Since this breed is defined
      as free of S. suis and a range of other endemic porcine pathogens, the
      experimental model could prove useful in the study of this infection.

PMID- 11506473
TI  - Acute viral lymphadenitis mimicking low-grade peripheral T-cell lymphoma. A
      clinicopathological study of nine cases.
AB  - Acute viral lymphadenitis, especially infectious mononucleosis (IM), often shows
      the presence of Reed-Sternberg-like cells, resulting in confusion with Hodgkin's
      disease. However, acute viral lymphadenitis requiring differential diagnosis from
      non-Hodgkin's lymphoma is not widely recognized. We describe the
      clinicopathological and immunohistochemical features of lymph node lesions from
      nine such patients which pose serious problems of differential diagnosis from low
      grade peripheral T-cell lymphoma. There were three males and six females with
      ages ranging from 21 to 44 years (median 25 years). All patients had "B" symptoms
      and multicentric lymphadenopathy. The clinical course was also self-limiting.
      Each lymph node specimen showed an obvious expansion of an interfollicular area
      by pleomorphic and polymorphous infiltration with an increased number of
      arborizing postcapillary venules. The infiltrate was composed of variable numbers
      of small and medium-sized lymphocytes, immunoblasts, plasma cells in various
      stage of maturation and occasional granulocytes. The small lymphocytes usually
      had regular round nuclei, whereas the medium-sized lymphocytes occasionally
      showed nuclear pleomorphism. Hyperreactivity of B-lymphocytes, including
      hyperplastic germinal centers and/or foci of monocytoid B-cells, was seen in
      parts of the lesion. The majority of the interfollicular T-lymphocytes, including
      T-immunoblasts, expressed CD8 antigen. Various numbers of TIA-1-positive small
      and medium-sized T-cells were observed in the paracortical area. Despite these
      findings, the overall histological picture of this series posed serious
      difficulties when differentially diagnosing this condition from low-grade
      peripheral T-cell lymphomas such as angioimmunoblastic T-cell (AILD) and T-zone
      types, indicating that viral lymphadenitis occasionally presents with
      histological features of AILD and T-zone lymphomas. To avoid overdiagnosis and
      overtreatment, we emphasize the need to pay careful attention to the clinical and
      laboratory findings as well as the morphological features.

PMID- 11506474
TI  - The prognostic importance of the nucleolar organizer region (AgNOR), Ki-67 and
      proliferating cell nuclear antigen (PCNA) in primary nonurachal bladder
      adenocarcinoma.
AB  - The aim of this study was to investigate the role of tumor proliferation in
      patients with nonurachal bladder adenocarcinoma. Samples were obtained from 16
      patients (12 men and 4 women, mean age 62 years) with primary nonrurachal bladder
      adenocarcinoma. The 16 formalin-fixed specimens were stained
      immunohistochemically for Ki-67 antigen and PCNA using MIB-1 and PC-10
      antibodies. In addition, the AgNOR quantity was assessed using the colloid silver
      nitrate staining technique in all cases. The Ki-67, PCNA and AgNOR proliferation
      indices were found to be significantly higher in high-grade and invasive tumors.
      The higher the grade (p<0.01) and stage (p<0.01), the higher were the
      proliferation indices. Patients whose tumor samples had a high Ki-67, PCNA and
      AgNOR proliferation index showed a higher incidence of local recurrence (p<0.01)
      and distant metastasis (p<0.01). In conclusion, our results suggest that Ki-67,
      PCNA and AgNOR proliferation scores may be important prognostic indices in
      nonurachal bladder adenocarcinomas.

PMID- 11506475
TI  - Macrophage and lymphocyte chimerism in bronchoalveolar lavage cells from human
      lung allograft recipients.
AB  - BACKGROUND: Chimerism is suggested to predict a more favourable prognosis in
      solid organ transplantation. MATERIAL AND METHOD: Forty-eight bronchoalveolar
      lavages from 10 patients (5 females and 5 males) who had received sex-mismatched
      donor lungs were monitored for varying periods of time, of up to 2 years, at
      regular intervals (median 3.0 (0.5-24) months). To investigate the chimerism in
      macrophages and lymphocytes in bronchoalveolar lavage cells a cloned 2.12
      kilobase large biotinylated Y-chromosome-specific DNA-probe was used for in situ
      hybridization. RESULTS: Donor macrophages disappeared in seven patients within
      the first 6 months after surgery (median 3.0 (1-6) months). But 15% donor
      macrophages could be detected in one patient 1 year and 10% in 2 patients two
      years after surgery. Donor lymphocytes disappeared in all patients within 3
      months (median 1 (0.5-3) months). There was no correlation between periods or
      severity of acute rejection and percentage of donor macrophages and donor
      lymphocytes in bronchoalveolar lavage. None of the patients developed
      obliterative bronchiolitis. CONCLUSION: Macrophage chimerism in lung may exist
      for several years. Whilst our results do not elucidate the role of local
      macrophage chimerism, they do not currently support the view that chimerism
      prevents rejection.

PMID- 11506476
TI  - RANTES in otitis media with effusion: presence, role and correlation with
      cytokines and microbiology.
AB  - Various inflammatory cells and cytokines have been identified in otitis media
      with effusion (OME). The presence of neutrophils has been linked to interleukin
      8, but no chemotactic factor has as yet been identified for monocytes. The
      chemokine RANTES (Regulated upon Activation, Normal T Expressed and Secreted)
      attracts and activates primarily monocytes and may contribute to the pathogenesis
      of middle ear inflammation. We investigated the presence of RANTES by: 1) ELISA
      measurement in 114 middle ear effusions from children suffering from OME, 2)
      immunohistochemical localisation in experimental OME rabbit middle ear mucosa,
      and 3) expression in cultured rabbit middle ear epithelium in response to
      proinflammatory stimuli. RANTES was detectable in 94 (82%) of 114 effusions with
      a median concentration of 79.7 pg/mg total protein content. The concentration of
      RANTES was positively correlated with the endotoxin content.
      Immunohistochemically, RANTES was localized to the epithelial layer in
      experimental OME. In vitro, RANTES was expressed in middle ear epithelium in
      response to proinflammatory stimuli (TNF-alpha) in a dose-dependent manner. The
      expression of RANTES may explain the recruitment of monocytes in OME, possibly as
      a result of TNF-alpha-mediated endotoxin stimulation.

PMID- 11506477
TI  - Genotypic detection of enterotoxigenic Escherichia coli colonisation factors.
AB  - We have developed a nonradioactive colony hybridisation assay for the detection
      of enterotoxigenic Escherichia coli (ETEC) that harbor the structural genes for
      CFA/I, CS1, CS2, CS4, CS17, or PCFO166. Thus, a polynucleotide probe derived from
      the colonisation factor antigen I (CFA/I) operon hybridised under very low
      stringency conditions to total DNA from CFA/I-producing (CFA/I), coli-surface
      antigen 1 and 3 (CS1 CS3-), CS2 CS3-, CS4 CS6-, CS17-, and putative colonisation
      factor O166 (PCFO166)-producing enterotoxigenic Escherichia coli (ETEC). The
      probe did not hybridise to DNA from CS3, CFA/III CS6, CS5 CS6, CS6, CS7, or
      PCFO159 ETEC. Visual registration of colour intensity could be used to
      differentiate between CFA/I, CS4 and PCFO166-positive strains on the one hand and
      strains with the genetic potential to express CS1, CS2, or CS17 on the other. As
      a confirmatory test, restriction fragment patterns obtained from Sau3AI-digested
      ETEC plasmid DNA could be used to distinguish between CFA/I, CS1, CS4, CS17, and
      PCFO166 ETEC in nonradioactive Southern blot hybridisation. The simultaneous
      genotypic detection of several ETEC colonisation factors will prove useful in
      vaccine-oriented studies of ETEC disease.

PMID- 11506478
TI  - Allele 2 of interleukin-1 receptor antagonist gene increases the risk of thyroid
      peroxidase antibodies in subacute thyroiditis.
AB  - Subacute granulomatous thyroiditis (SAT) is a self-limiting systemic inflammatory
      disorder with possible transient expression of thyroid antibodies. Persistent
      hypothyroidism is uncommon. The interleukin-1 receptor antagonist IL-1ra is an
      inhibitor of IL-1 activity and allele 2 of the IL-1ra gene is associated with
      inflammatory diseases and IL-1ra production. Forty-eight subjects with SAT were
      investigated. Polymorphisms of IL-1ra, IL-1beta-511 and TNFalpha genes were
      studied with respect to thyroid peroxidase antibodies (TPOab), thyroglobulin
      antibodies, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR).
      Serum IL-1ra levels were measured. An increased allelic frequency (43% vs 22%,
      p=0.039) and carriage rate (79% vs 41%, p=0.018) for IL-1ra allele 2 were
      observed with expression of TPOab in 14 (29.2%) subjects compared with those with
      negative findings. The carriage rate for both IL-1ra allele 2 and IL-1beta-511
      allele 2 was also increased with TPOab expression (71% vs 27%, p=0.004,
      respectively). No difference in allele frequency or carriage rate was found
      compared with healthy controls. Serum IL-1ra levels correlated with S-CRP
      (r=0.41, p=0.004) and ESR (r=0.34, p=0.016), but the association with genes or
      thyroid antibodies was statistically insignificant. S-CRP levels and ESR were
      lower and negatively correlated with expression of TPOab (r=-0.27, p=0.046 and r=
      0.32, p=0.017). This study describes the multiplicity of the mechanisms
      responsible for the severity of the acute-phase response during the course of
      SAT. IL-1ra may have a significant anti-inflammatory role in SAT. Presence of IL
      1ra allele 2 increases the risk of developing TPOab.

PMID- 11506479
TI  - Cloning, expression and antigenicity of the L. donovani reductase.
AB  - The protozoan parasite Leishmania undergoes a morphological and biochemical
      transformation from the promastigote to the amastigote form during its life
      cycle, which is reflected in the expression of stage-specific proteins. One of
      these proteins shows homology to a superfamily of reductase proteins. We have
      cloned the reductase gene from L donovani and have shown that it differs in only
      one nucleotide from the L. major homologue, resulting in one amino acid change. A
      cytosine (C) to guanine (G) transposition in the coding sequence leads to a
      nonconserved substitution of asparagine (N) for lysine (K). Only 2 of 22 plasma
      samples from patients with visceral leishmaniasis were found to have detectable
      anti-reductase antibodies and peripheral blood mononuclear cells (PBMC) from one
      of three individuals previously infected with visceral leishmaniasis proliferated
      in the presence of recombinant reductase protein. Interestingly, 6 of 10 PBMC
      isolated from Danish controls proliferated in the presence of the reductase
      protein. Intracellular IFNgamma was found in a significant percentage of cells in
      all the tested PBMC cultures from Danes, whereas IL4 was only found in a small
      proportion of cells, or not at all. The results indicate the presence of cross
      reacting CD45R0 memory T-cells in individuals not exposed to Leishmania. Several
      previous studies have shown that T-cells from nonexposed individuals often
      respond to crude Leishmania antigen preparations. The present study suggests that
      this reactivity is partly caused by T-cells recognising L. donovani reductase.

PMID- 11506480
TI  - Immunohistochemical detection of Fas and Fas ligand in sarcomatoid renal cell
      carcinoma.
AB  - Sarcomatoid renal cell carcinomas (SRC) are rare neoplasms associated with a very
      poor prognosis. The aim of this study was to evaluate biomarker expression and
      clinical significance in this uncommon renal cancer. Cytokeratin, epithelial
      membrane antigen, vimentin, desmin, smooth muscle actin, CD34, S-100 protein, MIB
      1, p53, Fas and Fas ligand immunohistochemical expression was investigated in
      seven renal cell carcinomas with sarcomatoid changes. No significant difference
      between sarcomatoid and nonsarcomatoid areas was observed with the different
      biomarkers, excepted for Fas ligand. Fas expression was diffuse in sarcomatoid
      and nonsarcomatoid areas. However, Fas ligand had a higher expression in
      sarcomatoid in comparison to nonsarcomatoid areas. Our results showed that Fas
      and Fas ligand are both expressed in renal cancer. We suggest that the aggressive
      behavior of sarcomatoid carcinoma may be related to a higher expression of Fas
      ligand by tumor sarcomatoid cells. These findings may indicate that Fas ligand is
      a possible therapeutic molecular target for treatment of SRC.

PMID- 11506481
TI  - Investigation of an outbreak caused by methicillin-resistant Staphylococcus
      aureus in a cardiovascular surgery unit by ribotyping, randomly amplifed
      polymorphic DNA and pulsed-field gel electrophoresis.
AB  - An outbreak caused by rapid spread of methicillin-resistant Staphylococcus aureus
      (MRSA) in an intensive care unit for cardiovascular surgery was investigated by
      phenotypic and genotypic methods. Fourteen isolates were collected during a 2
      month period from clinical and environmental specimens in the unit recently re
      opened after reconstruction. The isolates were tested for antibiotic
      susceptibility patterns and genotyped by automated ribotyping, randomly amplified
      polymorphic DNA-PCR (RAPD) analysis and pulsed-field gel electrophoresis (PFGE).
      Automated ribotyping applying EcoRI digestion proved to be of no value in
      separating the isolates. In contrast, PFGE grouped the isolates into four
      clusters different from the reference strain. These results fully correlated with
      the antibiograms. Twelve of the isolates were grouped into two clonally related
      clusters. RAPD analyses grouped the isolates into five clusters. Except for two
      isolates of one patient, which had different RAPD patterns, PFGE and RAPD
      analyses presented very similar results. The results verified the usefulness of
      PFGE in studies of MRSA epidemics. A combination of these two methods reduces the
      time to identification of an outbreak and increases the accuracy in detection of
      intraspecies differences.

PMID- 11506483
TI  - The pharmacologic basis of high dose chemotherapy with haematopoietic stem cell
      support for solid tumours.
AB  - The theoretical basis of high dose chemotherapy with haematopoietic stem cell
      support (HDT) for solid tumours is the presumption of a linear, steep dose
      response relationship for chemotherapy conditioning agents. We review preclinical
      pharmacologic studies evaluating steep dose-response relationships for different
      chemotherapeutic agents, identified through a MED-LINE and CANCER-LIT search of
      the English medical literature from January 1966 to December 1999. Only BCNU,
      melphalan, nitrogen mustard, and the combination of thiotepa and cyclophosphamide
      demonstrated steep dose-response relationships over a wide dose-range. The
      pharmacologic evidence for the use of other antineoplastic agents for HDT in
      solid tumours is non-existent. More preclinical studies are needed for a rational
      development of this therapeutic approach for solid tumours.

PMID- 11506484
TI  - Does surgery modify growth kinetics of breast cancer micrometastases?
AB  - Surgery should be considered as a major perturbing factor for metastasis
      development in laboratory animals. The different time distribution of mortality
      for 1173 patients undergoing mastectomy in comparison with 250 untreated patients
      suggests that primary tumour removal could result in changes of the metastatic
      process even for breast cancer.

PMID- 11506482
TI  - Chronic immune activation and inflammation as the cause of malignancy.
AB  - Several chronic infections known to be associated with malignancy have
      established oncogenic properties. However the existence of chronic inflammatory
      conditions that do not have an established infective cause and are associated
      with the development of tumours strongly suggests that the inflammatory process
      itself provides the prerequisite environment for the development of malignancy.
      This environment includes upregulation of mediators of the inflammatory response
      such as cyclo-oxygenase (COX)-2 leading to the production of inflammatory
      cytokines and prostaglandins which themselves may suppress cell mediated immune
      responses and promote angiogenesis. These factors may also impact on cell growth
      and survival signalling pathways resulting in induction of cell proliferation and
      inhibition of apoptosis. Furthermore, chronic inflammation may lead to the
      production of reactive oxygen species and metabolites such as malondialdehyde
      within the affected cells that may in turn induce DNA damage and mutations and,
      as a result, be carcinogenic. Here it is proposed that the conditions provided by
      a chronic inflammatory environment are so essential for the progression of the
      neoplastic process that therapeutic intervention aimed at inhibiting
      inflammation, reducing angiogenesis and stimulating cell mediated immune
      responses may have a major role in reducing the incidence of common cancers.

PMID- 11506485
TI  - Neuroblastoma in monozygotic twins--a case of probable twin-to-twin metastasis.
AB  - Concordance for neuroblastoma in monozygotic twins has been reported only rarely,
      and the cause of the shared pathology has not been established. We describe a
      case of infant monozygotic twins developing tumours that were morphologically,
      clinically and molecularly indistinguishable, but with a delay of 6 months
      between times of presentation. Both tumours were metastatic and had amplification
      of MYCN and deletion at 1p36. Twin 1, who developed neuroblastoma first, had
      constitutional karyotype abnormalities in at least 5% of peripheral blood
      mononuclear cells involving 1p and 3p, and a deletion of 1q44 in 21% of cells.
      Twin 2 had a normal constitutional karyotype and lacked rearrangement or deletion
      of these regions. We propose an acquired neuroblastoma predisposition specific
      for twin 1, and in utero metastatic spread of tumour cells to twin 2 via the
      shared placental circulation.

PMID- 11506486
TI  - Pain and health-related quality of life in a geographically defined population of
      men with prostate cancer.
AB  - In order to provide baseline data on pain and health-related quality of life, to
      explore factors predicting pain and reduced quality of life, and to find
      potentially undertreated cases in men with prostate cancer, we undertook a
      population-based questionnaire study. The questionnaire, which included the
      EuroQo1 instrument, the Brief Pain Inventory form and 8 specially designed
      questions, was sent to all men with prostate cancer in the county of
      Ostergotland, Sweden. Of the 1442 men included in the study, 1243 responded to
      the questionnaire. Altogether 42% had perceived pain during the previous week and
      26% stated their quality of life to be 50% or lower on a visual analogue scale. A
      high rating of health care availability and short time since diagnosis were found
      to significantly predict lower ratings of pain (P< 0.05). Pain was found to be a
      significant predictive factor for decreased quality of life together with high
      age, low rating of health care availability and palliative treatment (P< 0.05).
      In conclusion, assessment and treatment of pain is essential for a good quality
      of life in men with prostate cancer. The monitoring of prostate cancer patients
      should be individualized to fit the demands of the groups with the greatest need
      for support.

PMID- 11506487
TI  - Liver metastases from colorectal cancer: regional intra-arterial treatment
      following failure of systemic chemotherapy.
AB  - This study was designed to determine response rate, survival and toxicity
      associated with combination chemotherapy delivered intra-arterially to liver in
      patients with hepatic metastases of colorectal origin refractory to standard
      systemic treatment. A total of 28 patients who failed prior systemic treatment
      with fluoropyrimidines received a median of 5 cycles of intra-arterial treatment
      consisting of 5-fluorouracil 700 mg/m(2)/d, leucovorin 120 mg/m(2)/d, and
      cisplatin 20 mg/m(2)/d for 5 consecutive days. Cycles were repeated at intervals
      of 5-6 weeks. A major response was achieved in 48% of patients: complete response
      in 8% and partial response in 40%. The median duration of response was 11.5
      months. Median survival was 12 months at a median follow up of 12 months. On
      multivariate analysis, the only variables with a significant impact on survival
      were response to treatment and performance status. Toxicity was moderate: grades
      III-IV neutropenia occurred in 29% of patients. Most of the patients complained
      of fatigue lasting for a few days following each cycle. There were no cases of
      hepatobiliary toxicity. These findings indicate that regional intra-arterial
      treatment should be considered in selected patients with predominantly liver
      disease following failure of standard treatment.

PMID- 11506488
TI  - Factors predicting efficacy of oxaliplatin in combination with 5-fluorouracil (5
      FU) +/- folinic acid in a compassionate-use cohort of 481 5-FU-resistant advanced
      colorectal cancer patients.
AB  - A statistical analysis was performed on the patient data collected from two
      compassionate-use programmes using oxaliplatin (Eloxatin(R)) + 5-fluorouracil (5
      FU) +/- folinic acid (FA), to identify predictive factors for oxaliplatin-based
      salvage treatment in patients with 5-FU-resistant advanced colorectal cancer
      (ACRC). 481 5-FU-resistant ACRC patients, most with performance status < or = 2,
      > or = 3 involved sites, and > or = 2 prior lines of chemotherapy, received
      oxaliplatin + 5-FU +/- FA. Prognostic factors associated with overall response
      rate (ORR), time to progression (TTP) and overall survival (OS) were identified
      using univariate and multivariate logistic and/or Cox proportional hazards
      analyses. The ORR was 16% (95% CI: 13-20), the median TTP was 4.2 months (95% CI:
      3.4-4.6), and the median OS was 9.6 months (95% CI: 8.6-10.6). The multivariate
      analysis indicated poor (> or = 2 WHO) performance status (PS), a large number of
      prior chemotherapy regimens (> or = 3), a low baseline haemoglobin level (< 10
      g/dl), and a triweekly (vs biweekly) treatment administration schedule as
      significantly associated (P< 0.05) with a lower ORR. Sex (male), number of organs
      involved (> or =3) and alkaline phosphatase (AP) level (> or = 2 x the upper
      limit of normal) were associated (P< 0.05) with shorter TTP. Poor PS, a large
      number of organs involved, and elevated AP were independently and significantly
      correlated with shorter OS. Our analysis identified a relationship between
      efficacy results of oxaliplatin + 5-FU +/- FA treatment in 5-FU-resistant ACRC
      patients and baseline prognostic factors related to PS, extent of disease and
      number of prior regimens.

PMID- 11506489
TI  - IL-6 gene amplification and expression in human glioblastomas.
AB  - The aggressiveness of human gliomas appears to be correlated with the
      upregulation of interleukin 6 (IL-6) gene. Using quantitative PCR methods, we
      detected amplification and expression of the IL-6 gene in 5 of 5 primary
      glioblastoma samples and in 4 of 5 glioblastoma cell lines. This finding suggests
      that the amplification of IL-6 gene may be a common feature in glioblastomas and
      may contribute to the IL-6 over-expression.

PMID- 11506490
TI  - Genetic analysis of the APC gene regions involved in attenuated APC phenotype in
      Israeli patients with early onset and familial colorectal cancer.
AB  - The genetic basis for the majority of early onset or non-syndromic "familial"
      colorectal cancer (CRC) is unknown. Attenuated APC phenotype is characterized by
      relatively few colonic polyps, early age at onset of colon cancer compared with
      the general population, and inactivating germline mutations within specific
      regions of the APC gene. We hypothesized that germline mutations within these APC
      gene regions, might contribute to early onset or familial CRC susceptibility. To
      test this notion, we analysed 85 Israeli patients with either early onset (< 50
      years at diagnosis) or familial CRC for harbouring mutations within the relevant
      APC gene regions: exons 1-5, exon 9 and a region within exon 15 (spanning
      nucleotides c.3900 to c.4034; codons 1294 to 1338) using denaturing gradient gel
      electrophoresis (DGGE), and all of exon 15 employing protein truncation test
      (PTT). No inactivating, disease-associated mutations were detected in any
      patient. A novel polymorphism in intron 5 was detected in 16 individuals, 8
      patients were carriers of the 11307K variant, a mutation prevalent among Jewish
      individuals with colorectal cancer, and 4 displayed the E1317Q variant. We
      conclude that in Israeli individuals with early onset or familial CRC, truncating
      mutations in the APC gene regions associated with attenuated APC phenotype
      probably contribute little to disease pathogenesis.

PMID- 11506491
TI  - A common founder for the V126D CDKN2A mutation in seven North American melanoma
      prone families.
AB  - One of the most common melanoma-related CDKN2A mutations reported in North
      America is the V126D mutation. We examined nine markers surrounding CDKN2A in
      three American and four Canadian families carrying the V126D mutation. All seven
      families had a haplotype consistent with a common ancestor/founder for this
      mutation. In addition, the mutation appears to have originated 34-52 generations
      ago (1-LOD-unit support interval 13-98 generations).

PMID- 11506492
TI  - Neuroblastomas with chromosome 11q loss and single copy MYCN comprise a
      biologically distinct group of tumours with adverse prognosis.
AB  - Neuroblastoma is a heterogeneous tumour and its effective clinical management is
      dependent on accurate prognostic evaluation. In approximately 25% of patients
      amplification of the MYCN oncogene is known to be associated with a poor outcome.
      In order to identify additional molecular markers with prognostic potential in
      non-MYCN-amplified neuroblastomas, we looked for a correlation between clinical
      outcome and loss of heterozygosity (LOH) on four chromosomes that frequently show
      alteration in neuroblastoma (chromosomes 3, 4, 11 and 14). Chromosome 11q loss
      (with frequent parallel loss of chromosomes 3p, 4p and/or 14q) was found
      exclusively in tumours without MYCN amplification and was significantly
      associated with poor event-free survival. The 2-year event-free survival rate for
      11q LOH cases was 30%, compared to 34% for MYCN-amplified cases and 100% for
      cases without these abnormalities. While 11q LOH was associated predominantly
      with advanced-stage disease, 2 cases with low-stage disease and 11q LOH both
      suffered relapses. We conclude that chromosome 11q loss defines a biologically
      distinct group of tumours without MYCN amplification that appear to have
      potential for aggressive metastatic growth. Thus this genetic alteration may be
      an important new prognostic marker in neuroblastoma.

PMID- 11506493
TI  - Molecular profiles of BRCA1-mutated and matched sporadic breast tumours: relation
      with clinico-pathological features.
AB  - About 5-10% of breast cancers are hereditary; a genetically and clinically
      heterogeneous disease in which several susceptibility genes, including BRCA1,
      have been identified. While distinct tumour features can be used to estimate the
      likelihood that a breast tumour is caused by a BRCA1 germline mutation it is not
      yet possible to categorize a BRCA1 mutated tumour. The aim of the present study
      is to molecularly classify BRCA1 mutated breast cancers by resolving gene
      expression patterns of BRCA1 and matched sporadic surgical breast tumour
      specimens. The expression profiles of 6 frozen breast tumour tissues with a
      proven BRCA1 gene mutation were weighed against those from 12 patients without a
      known family history but who had similar clinico-pathological characteristics. In
      addition two fibroblast cultures, the breast cancer cell-line HCC1937 and its
      corresponding B-lymphoblastoid cell line (heterozygous for mutation BRCA1
      5382insC) and an epithelial ovarian cancer cell line (A2780) were studied. Using
      a high density membrane based array for screening of RNA isolated from these
      samples and standard algorithms and software, we were able to distinguish
      subgroups of sporadic cases and a group consisting mainly of BRCA1-mutated breast
      tumours. Furthermore this pilot analysis revealed a gene cluster that
      differentially expressed genes related to cell substrate formation, adhesion,
      migration and cell organization in BRCA1-mutated tumours compared to sporadic
      breast tumours.

PMID- 11506494
TI  - Expression of Rb2/p130 in breast and endometrial cancer: correlations with
      hormone receptor status.
AB  - Rb2/p130 is a member of the retinoblastoma family of proteins, consisting of Rb,
      Rb2 and p107, which are important negative regulators of cell cycle progression
      and differentiation. While Rb2 downregulation was observed in several malignant
      tumours including endometrial cancer, the role of p130 in breast carcinomas is
      still unknown. We investigated Rb2 protein expression in tumour tissue from 68
      mammary and 41 endometrial carcinomas, 4 mammary cell lines, and normal tissue
      samples. Therefore, we performed Western blot experiments for Rb2, Rb, and the
      oestrogen and progesterone receptors (ER, PR-A, PR-B). Weak or absent Rb2
      expression was more often found in endometrial (59%) than in mammary carcinomas
      (24%). We found significant positive correlations of Rb2 expression with Rb, ER,
      and PR-B in breast cancer samples, and of Rb2 with Rb, PR-A, PR-B, and younger
      age in endometrial carcinomas. No significant associations with histological
      grading, stage, nodal involvement, or Ki67 staining were detected. Rb2 mRNA
      expression was studied by semi-quantitative RT-PCR in 56 endometrial or mammary
      tissue samples and correlated significantly with Western blot results. Our
      results indicate that loss of Rb2 expression, mostly by transcriptional down
      regulation, may be associated with the development and dedifferentiation of most
      endometrial and a subset of mammary carcinomas.

PMID- 11506495
TI  - Prognostic utility of human complement factor H related protein test (the BTA
      stat Test).
AB  - The purpose of the study was to determine, in addition to well-known prognostic
      factors, histological grade, stage, tumour size and multiplicity, the correlation
      of BTA stat Test on disease free interval (DFI) on primary superficial bladder
      cancer. A total of 116 patients with newly diagnosed bladder cancer were
      evaluated in a prospective multicentre study. A voided urine sample was obtained
      prior to TURB and split for culture, cytology and BTA stat testing. Follow-up
      data for the patients were collected until the first recurrence or the last visit
      and the DFI was analysed by Kaplan-Meier method and Cox analysis. Ninety-seven of
      the 116 (83.6%) patients were eligible for analysis. The BTA stat Test was
      positive in 73 (75.3%) patients, whereas cytology detected 20 (20.6%) cases. The
      DFI was found to be shorter among patients with a positive BTA stat Test, and
      also among those with intermediate or high-grade tumours. The BTA stat Test
      result divided patients with grade 2 tumours into two prognostic groups, in that
      those testing positive had 68.6% risk of recurrence during the first year
      compared to 42.9% risk of those with a negative test result (P = 0.041). Although
      the effect of tumour size on DFI was notable, the difference did not reach
      statistical significance (P = 0.064). Number of tumours was not related to DFI,
      nor was the difference between different stage of tumour of significance. BTA
      stat Test is not only sensitive in detection of primary bladder cancer, but also
      might have some independent prognostic significance.

PMID- 11506496
TI  - Frequency of PSA-mRNA-bearing cells in the peripheral blood of patients after
      prostate biopsy.
AB  - Transrectal ultrasound (TRUS) guided prostate biopsy is standard diagnostic
      procedure for prostate cancer (PCa). However, possibility of dissemination of
      cancer cells by biopsy is not negligible. To investigate this possibility, we
      examined prostate specific antigen (PSA)-bearing cells in peripheral blood of the
      108 patients before and after prostate biopsy. Peripheral blood samples were
      obtained from 108 patients with elevated serum PSA (sPSA) levels, who had
      undergone sextant prostate biopsy using TRUS. The presence of PSA-mRNA bearing
      cells was examined using the nested RT-PCR method enabling detection of one LNCaP
      cell diluted in 1 ml of whole blood. Among 108 patients, 62 and 46 were diagnosed
      with benign prostatic hyperplasia (BPH) and PCa, respectively. PSA-mRNA was
      detected in 3 PCa cases but in no BPH patients before and after biopsy, and in 16
      BPH (25.8%) and in 21 PCa (45.7%) patients only after biopsy (P< 0.01). The
      patients with positive mRNA before biopsy had higher sPSA (P< 0.001), and those
      after biopsy had higher sPSA and PSA density (PSAD) levels (P< 0.05). Positive
      PSA-mRNA cases had more cancer involved biopsy cores than the negative PSA-mRNA
      cases (P< 0.001). Although further investigations are needed, the present
      findings suggest that prostate biopsy might scatter prostate cells in the blood
      stream especially in cases with high sPSA and, thus, might contribute to tumour
      spreading in the cases of prostate cancer.

PMID- 11506497
TI  - Hypomethylation of the MN/CA9 promoter and upregulated MN/CA9 expression in human
      renal cell carcinoma.
AB  - MN/CA9 is a cancer-related gene, frequently activated in human renal cell
      carcinomas (RCCs). To reveal the activation mechanism, we investigated the
      relationship between methylation status of the MN/CA9 promoter region and gene
      expression using 13 human RCCs, and examined the effect of in vitro CpG
      methylation on the MN/CA9 promoter activity using a human RCC cell line (SK-RC
      44), expressing MN/CA9. MN/CA9 expression was evaluated by RT-PCR and observed in
      10 of 13 RCCs (77%). A total of 9 out of 10 MN/CA9 -positive RCCs (90%) contained
      clear cell components. Methylation status of 6 CpGs in the MN/CA9 promoter region
      was decided by using the bisulfite genomic sequencing protocol. Out of 13 RCCs 9
      (69%) showed partial hypomethylation of the CpG at -74 bp, while the other 4 RCCs
      and 3 normal kidney tissue samples showed complete methylation. Hypomethylation
      of the CpG at -74 bp was strongly correlated with MN/CA9 expression. Luciferase
      assay revealed that the MN/CA9 promoter activity was strongly suppressed by
      methylation of the CpG at -74 bp. These findings suggest that hypomethylation of
      the CpG at -74 bp in the MN/CA9 promoter region might play an important role in
      this gene activation of human RCC.

PMID- 11506498
TI  - Functional analysis of the mismatch repair system in bladder cancer.
AB  - In bladder cancer the observed microsatellite instability indicates that mismatch
      repair deficiency could be a frequently involved factor in bladder cancer
      progression. To investigate this hypothesis we analysed extracts of seven bladder
      cancer cell lines and, as a novel approach, five clinical cancer samples for
      mismatch repair activity. We found that one cell line (T24) and three of the
      clinical samples had a reduced repair capacity, measured to approximately 20% or
      less. The T24 cell extract was unable to repair a G-G mismatch and showed reduced
      repair of a 2-base loop, consistent with diminished function of the MSH2-MSH6
      heterodimer. The functional assay was combined with measurement for mutation
      frequency, microsatellite analysis, sequencing, MTT assay, immunohistochemical
      analysis and RT-PCR analysis of the mismatch repair genes MSH2, MSH3, MSH6, PMS1,
      PMS2 and MLH1. A >7-fold relative increase in mutation frequency was observed for
      T24 compared to a bladder cancer cell line with a fully functional mismatch
      repair system. Neither microsatellite instability, loss of repair nor mismatch
      repair gene mutations were detected. However, RT-PCR analysis of mRNA levels did
      detect changes in the ratio of expression of the Mut S and Mut L homologues. The
      T24 cell line had the lowest MSH6 expression level of the cell lines tested.
      Identical RT-PCR analysis of seventeen clinical samples (normal urothelium, 7;
      pTa low stage, 5; and pT1-4 high stage, 5) indicated a significant change in the
      expression ratio between MSH3/MSH6 (P< 0.004), MSH2/MSH3 (P< 0.012) and PMS2/MLH1
      P< 0.005, in high stage bladder tumours compared to normal urothelium and low
      stage tumours. Collectively, the data suggest that imbalanced expression of
      mismatch repair genes could lead to partial loss of mismatch repair activity that
      is associated with invasive bladder cancer.

PMID- 11506499
TI  - Correlation of vascular endothelial growth factor expression with fibroblast
      growth factor-8 expression and clinico-pathologic parameters in human prostate
      cancer.
AB  - Vascular endothelial growth factor (VEGF) mediates neo-angiogenesis during tumour
      progression and is known to cooperate with the fibroblast growth factor (FGF)
      system to facilitate angiogenesis in a synergistic manner. In view of this, we
      have investigated VEGF expression in 67 cases of prostate cancer previously
      characterized for fibroblast growth factor-8 (FGF-8) expression. Cytoplasmic VEGF
      staining was detected in malignant cells in 45 out of 67 cases. Cytoplasmic
      staining was found in adjacent stromal cells in 32 cases, being particularly
      strong around nests of invasive tumour. Positive VEGF immunoreactivity in benign
      glands was restricted to basal epithelium. A significant association was observed
      between tumour VEGF and FGF-8 expression (P = 0.004). We identified increased
      VEGF immunoreactivity in both malignant epithelium and adjacent stroma and both
      were found to be significantly associated with high tumour stage (P = 0.0047 and
      P = 0.0002, respectively). VEGF expression also correlated with increased serum
      PSA levels (P = 0.01). Among positively stained tumours, VEGF expression showed a
      significant association with Gleason score (P = 0.04). Cases showing positive
      VEGF immunoreactivity in the stroma had a significantly reduced survival rate
      compared to those with negative staining (P = 0.037). Cases with tumours
      expressing both FGF-8 in the malignant epithelium and VEGF in the adjacent stroma
      had a significantly worse survival rate than those with tumours negative for
      both, or only expressing one of the two growth factors (P = 0.029). Cox
      multivariate regression analysis of survival demonstrated that stromal VEGF and
      tumour stage were the most significant independent predictors of survival. In
      conclusion, we report for the first time a correlation of both tumour and stromal
      VEGF expression in prostate cancer with clinical parameters as well as its
      correlation to FGF-8 expression.

PMID- 11506500
TI  - Inhibited growth of colon cancer carcinomatosis by antibodies to vascular
      endothelial and epidermal growth factor receptors.
AB  - Vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF)
      regulate colon cancer growth and metastasis. Previous studies utilizing
      antibodies against the VEGF receptor (DC101) or EGF receptor (C225) have
      demonstrated independently that these agents can inhibit tumour growth and induce
      apoptosis in colon cancer in in vivo and in vitro systems. We hypothesized that
      simultaneous blockade of the VEGF and EGF receptors would enhance the therapy of
      colon cancer in a mouse model of peritoneal carcinomatosis. Nude mice were given
      intraperitoneal injection of KM12L4 human colon cancer cells to generate
      peritoneal metastases. Mice were then randomized into one of four treatment
      groups: control, anti-VEGFR (DC101), anti-EGFR (C225), or DC101 and C225.
      Relative to the control group, treatment with DC101 or with DC101+C225 decreased
      tumour vascularity, growth, proliferation, formation of ascites and increased
      apoptosis of both tumour cells and endothelial cells. Although C225 therapy did
      not change any of the above parameters, C225 combined with DC101 led to a
      significant decrease in tumour vascularity and increases in tumour cell and
      endothelial cell apoptosis (vs the DC101 group). These findings suggest that
      DC101 inhibits angiogenesis, endothelial cell survival, and VEGF-mediated ascites
      formation in a murine model of colon cancer carcinomatosis. The addition of C225
      to DC101 appears to lead to a further decrease in angiogenesis and ascites
      formation. Combination anti-VEGF and anti-EGFR therapy may represent a novel
      therapeutic strategy for the management of colon peritoneal carcinomatosis.

PMID- 11506501
TI  - Prostate epithelial cell lines form spheroids with evidence of glandular
      differentiation in three-dimensional Matrigel cultures.
AB  - Normal (PNT2-C2) and metastatic (PC-3) prostate cell lines were grown in Matrigel
      to observe the effects on morphology and phenotype in comparison to monolayer
      culture. In monolayer cultures, PNT2-C2 showed typical round/cuboidal epithelial
      morphology, with tight cell associations, whereas in Matrigel they formed smooth
      spheroids, tightly packed with cells. In both monolayer and Matrigel, PNT2-C2 had
      a differentiated luminal epithelial phenotype with high expression of cytokeratin
      8, prostate specific antigen (PSA), prostate specific membrane antigen (PSMA), E
      cadherin and desmoglein. In contrast, PC-3 cells possessed an
      epithelial/mesenchyme morphology in monolayer with loose cell to cell contact and
      pseudopodial extensions. Immunohistochemical phenotyping indicated the cells were
      undifferentiated, expressing high levels of vimentin, beta1 integrin, CD44 and
      low expression of cytokeratin 8. In Matrigel they formed smooth and irregular
      spheroids, which had a lumen surrounded by a single cell layer. Matrigel also
      influenced the expression of PSA, PSMA and CD44. These results indicate that
      Matrigel culture can induce morphological differentiation of prostate cancer
      cells which initially had a basal phenotype.

PMID- 11506502
TI  - Hyaluronan production increases the malignant properties of mesothelioma cells.
AB  - Malignant pleural mesotheliomas is in most cases associated with elevated amounts
      of hyaluronan. To investigate the importance of hyaluronan for the malignant
      properties of mesotheliomas, we have expressed murine hyaluronan synthase 2
      (HAS2) in the non-hyaluronan producing mesothelioma cell line, Mero-25. We found
      that upon hyaluronan overproduction the mesothelioma cells changed their
      epitheloid character to a fibroblastic phenotype and were surrounded by
      pericellular matrices, the size of which correlated to the amount of synthesized
      hyaluronan. HAS2-transfected cells with the ability to synthesize about 520 ng
      hyaluronan/5 x 10(4)cells/24 h exhibited about a 2-fold increase in the
      expression of the cell surface hyaluronan receptor CD44 and their locomotion
      increased compared to that of mock-transfected Mero-25 cells. Furthermore, the
      malignant properties of mesothelioma cell clones as determined by the ability to
      grow in a soft agar assay correlated to their hyaluronan production. These
      results provide evidence for an important role of hyaluronan in the aggressive
      spread of mesotheliomas in adjacent non-cancerous stromal tissues.

PMID- 11506503
TI  - An orthotopic xenograft model of human nonseminomatous germ cell tumour.
AB  - We have established the first example of an orthotopic xenograft model of human
      nonseminomatous germ cell tumour (NSGCT). This reproducible model exhibits many
      clinically relevant features including metastases to the retroperitoneal lymph
      nodes and lungs, making it an ideal tool for research into the development and
      progression of testicular germ cell tumours.

PMID- 11506504
TI  - Enhanced VEGF production and decreased immunogenicity induced by TGF-beta 1
      promote liver metastasis of pancreatic cancer.
AB  - TGF-betas are multifunctional polypeptides that regulate cell growth and
      differentiation, extracellular matrix deposition, cellular adhesion properties,
      angiogenesis and immune functions. In this study, we investigated the effect of
      TGF-beta1 on liver metastasis and its mechanism by using human pancreatic cancer
      cell lines Panc-1, Capan-2, and SW1990. Capan-2 and SW1990 cells demonstrated
      enhanced liver metastatic potential by in vivo splenic injection with TGF-beta1.
      Consequently, we examined the role of TGF-beta1 on in vitro angiogenesis and
      received cytotoxicity by peripheral blood mononuclear leukocytes (PBMLs). While
      TGF-beta1 slightly decreased cell proliferation, it also upregulated VEGF
      production in all cancer cells examined. The binding of PBMLs to cancer cells and
      cancer cell cytotoxicity during co-culture with PBMLs were remarkably decreased
      by treatment with TGF-beta1. Panc-1 cells revealed no liver metastasis despite
      their high immunogenetic and angiogenetic abilities, which was attributed to a
      lack of expression of the cell surface carbohydrates that induce attachment to
      endothelial cells. We concluded that the presence of TGF-beta1 in the
      microenvironment of tumour site might play an important role in enhancing liver
      metastasis of pancreatic cancer by modulating the capacity of angiogenesis and
      immunogenicity.

PMID- 11506506
TI  - The chemopotentiation of cisplatin by the novel bioreductive drug AQ4N.
AB  - AQ4N is a bioreductive drug that can significantly enhance the anti-tumour effect
      of radiation and cyclophosphamide. The aim of this study was to examine the
      ability of AQ4N to potentiate the anti-tumour effect of cisplatin and to compare
      it to the chemopotentiation effect of tirapazamine. In the T50/80 murine tumour
      model, AQ4N (50-100 mg/kg) was administered 30 min, 2.5 or 6 h prior to cisplatin
      (4 mg/kg or 8 mg/kg); this produced an anti-tumour effect that was approximately
      1.5 to 2 times greater than that achieved by a single 4 or 8 mg/kg dose of
      cisplatin. Tirapazamine (25 mg/kg) administered 2.5 h prior to cisplatin (4
      mg/kg) resulted in a small increase in anti-tumour efficacy. AQ4N was also
      successful in enhancing the anti-tumour effect of cisplatin in the SCCVII and RIF
      1 murine tumour models. This resulted in an increased cell kill of greater than 3
      logs in both models; this was a greater cell kill than that observed for
      tirapazamine with cisplatin. Combination of cisplatin with AQ4N or tirapazamine
      resulted in no additional bone marrow toxicity compared to cisplatin administered
      alone. In conclusion, AQ4N has the potential to improve the clinical efficacy of
      cisplatin.

PMID- 11506505
TI  - Differences between human breast cell lines in susceptibility towards growth
      inhibition by genistein.
AB  - Genistein is thought to contribute to the putative breast cancer preventive
      activity of soya. The mechanisms by which it arrests the growth of breast cells
      are incompletely understood. In order to explore generic features of the
      modulation of human breast cell growth by genistein, its effects on cell lines
      MCF-7, ZR-75.1, T47-D, MDA-MB 468, MDA-MB 231 and HBL 100 were compared.
      Genistein at 1 microM stimulated growth only in MCF-7 cells. At 10 microM it
      arrested the growth of all 6 cell types, however that of T47-D and HBL 100 cells
      only in medium with reduced (2%) fetal calf serum. Genistein induced apoptosis in
      only MDA-MB 468 cells. It arrested cells in the G2 stage of the cell cycle in all
      cell lines except ZR-75.1. Cells differed in their susceptibility towards
      inhibition by genistein of phorbol ester-induced proto-oncogene c-fos levels,
      transcription factor activator protein-1 (AP-1) activity and extracellular signal
      regulated kinase (ERK) activity. Genistein augmented anisomycin-induced levels of
      proto-oncogene c-jun in ZR 75.1 and MCF-7 cells. The results suggest that
      induction of apoptosis, G2 cell cycle arrest and inhibition of c-fos expression,
      AP-1 transactivation and ERK phosphorylation may contribute to the growth
      inhibitory effect of genistein in some breast cell types, but none of these
      effects of genistein constitutes a generic mode of growth-arresting action.

PMID- 11506507
TI  - Metabolism and growth inhibition of four retinoids in head and neck squamous
      normal and malignant cells.
AB  - Isotretinoin (13-cis-retinoic acid, 13cRA) has proven to be active in
      chemoprevention of head and neck squamous cell carcinoma (HNSCC). Moreover, both
      all-trans-retinoic acid (ATRA) and 13cRA induce objective responses in oral
      premalignant lesions. After binding of retinoids to retinoic acid receptors (RARs
      and RXRs) dimers are formed that are able to regulate the expression of genes
      involved in growth and differentiation. We compared the metabolism and level of
      growth inhibition of 13cRA with that of ATRA, 9cRA and retinol in four HNSCC cell
      lines and normal oral keratinocyte cultures (OKC). These retinoid compounds are
      known to bind with different affinities to the retinoic acid receptors. We
      observed that all retinoids were similar with respect to their capacity to induce
      growth inhibition. One HNSCC line could be ranked as sensitive, one as moderately
      sensitive and the remaining two were totally insensitive; OKC were moderately
      sensitive. The rate at which the cells were able to catabolize the retinoid was
      similar for all compounds. Retinoid metabolism in HNSCC cells resulted in a
      profile of metabolites that was unique for each retinoid. These metabolic
      profiles were different in OKC. Our findings indicate that differences in
      retinoid receptor selectivity of these retinoids do not influence the level of
      growth inhibition and rate of metabolism.

PMID- 11506509
TI  - Arterio-ureteral fistula--a systematic review.
AB  - OBJECTIVE: To review published reports on arterio-ureteral fistula. METHOD:
      Literature search. RESULTS: Eighty cases were identified. Primary fistulas were
      mainly seen in combination with aortoiliac aneurysmal disease. Secondary fistulas
      were seen after pelvic cancer surgery, often with radiation, fibrosis and
      ureteral stenting or after vascular surgery with synthetic grafting. The
      dominating symptom is massive haematuria, often with circulatory impairment. The
      clue to a rapid and correct diagnosis is a high degree of suspicion. Most
      frequently diagnosis has been obtained through angiography or pyelography. When
      there is a ureteral stent manipulation it will often provoke bleeding and lead to
      diagnosis. The fistula must be excluded and a vascular reconstruction made. Most
      frequently this has been obtained through occlusion of the fistula and an extra
      anatomic reconstruction (femoro-femoral crossover). Recently stent-grafting has
      been successfully used but follow-up is short. CONCLUSION: Arterio-ureteral
      fistula is rare and should be suspected in patients with complicated pelvic
      surgery and massive haematuria, especially where rigid ureteral stents have been
      placed.

PMID- 11506510
TI  - Literature review of surgical management of abdominal aortic aneurysm.
AB  - OBJECTIVES: To review the natural history and the outcome of surgical repair of
      aortic abdominal aneurysm (AAA). DESIGN: An English and Scandinavian language
      search of papers between 1985-1997. RESULTS: After review, 132 papers with 54 048
      patients remained. The mean postoperative mortality (30 days or in-hospital) for
      elective repair was approximately 5% and for emergency operations 47% (range 27
      69%), both with significant heterogeneity. Results did not improve over time.
      Increasing age, presence of renal failure and atherosclerotic cardiac disease
      were identified as pre-operative risk factors. AAA expansion averaged 0.2-0.4 cm
      per year for aneurysms smaller than 4 cm, 0.2-0.5 cm for aneurysms 4-5 cm and 0.3
      0.7 cm for those larger than 5 cm. The rupture risk at four years was 2, 10 and
      22% respectively. The overview revealed several methodological problems in the
      reported studies. CONCLUSIONS: The results can be used as the basis of quality
      assurance or in decision trees or other models. Better reporting standards are
      needed.

PMID- 11506511
TI  - Endovascular treatment of severe symptomatic stenosis of the internal carotid
      artery: early and late outcome.
AB  - OBJECTIVES: To report a 6 year experience with carotid percutaneous transluminal
      angioplasty (CPTA) in a selected group of patients. MATERIAL AND METHOD: We
      retrospectively reviewed our experience after performing 54 CPTAs, with (n=18) or
      without (n=36) stent deployment, over a period of 6 years from 1993 to 1999. All
      patients, except one, suffered from focal hemispheric neurologic symptoms. During
      the same time period 284 patients underwent carotid endarterectomy. The selection
      of the 54 patients (16%) for CPTA was based on the carotid angiogram and the sole
      inclusion criterion for endovascular treatment was a short, concentric, and
      smooth stenosis of more than 70% without ulceration or severe calcification. All
      patients who had a patent internal carotid artery after the last control were
      invited for a clinical duplex examination and all duplex examinations were
      carried out by a single experienced observer. RESULTS: Early outcome (<30 days):
      CPTA was judged technically successful in 50 cases (93%). Ten patients (18%)
      experienced a neurological event in relation to the procedure and one patient
      (2%) suffered a major stroke. One stent occluded within 30 days. LATE OUTCOME:
      Forty-six patients (85%) entered the follow-up study after a median of 34 months
      (range 1-80 months). Six patients (13%) had recurrent symptoms. The colour-duplex
      examination (n=45) showed internal carotid artery occlusion in 2 patients (5%),
      and restenosis (>70%) in 10 patients (22%). We found no significant difference in
      the reoccurrence of neurological symptoms or the rate of restenosis between
      patients treated with and without stent (Log Rank 0.28, p=0,59). ICA was patent
      without restenosis in 60% after 48 months in patients treated with CPTA alone,
      and in 76% after 3 months in patients treated with a stent (N.S.). CONCLUSION:
      CPTA in a selected group of patients has a mortality and major stroke rate
      comparable to that of carotid endarterectomy. However, the risk of transient
      neurological events was high, as well as the incidence of restenosis (>70%) after
      3 years. We still consider CPTA an experimental procedure. The indications for
      this treatment must be clarified if CPTA should be an alternative to surgery with
      a comparable neurological complication rate.

PMID- 11506512
TI  - The impact of MRSA on vascular surgery.
AB  - OBJECTIVES: To investigate the prevalence of MRSA infection in patients treated
      in a major vascular unit and examine its consequences. DESIGN AND METHODS: A
      retrospective case-note review was performed. RESULTS: During the period 1993 to
      2000, a total of 172 patients (4.4% of total) were positive for MRSA. Of these 97
      were colonised and 75 were infected by MRSA. The proportion of wound or graft
      infections caused by MRSA has increased (4% in 1994 to 63% in 2000). Three
      patients developed native artery infection (one following aortic stent insertion
      and 2 following embolectomy). All patients with aortic graft infection died. All
      patients with infected prosthetic infrainguinal bypass ended up with an
      amputation. CONCLUSION: The prevalence of MRSA infection is increasing. Infection
      of aortic grafts appears to be uniformly fatal and lower limb graft infection is
      associated with high limb loss.

PMID- 11506513
TI  - Methicillin resistant Staphylococcus aureus in patients undergoing major
      amputation.
AB  - OBJECTIVES: To examine the impact of MRSA infection on patients undergoing major
      amputation. SETTING: District General Hospital. METHODS: Patients having had
      major amputation and positive MRSA cultures January 1995-December 1999 were
      included. Outcome was compared with a randomly chosen group of patients having
      major amputation but no positive MRSA culture from the same time period. RESULTS:
      overall 21% of patients undergoing amputation were MRSA positive. Some 28
      patients (30 amputations) with MRSA positive cultures were compared with 44
      patients (54 amputations) who did not have positive cultures for MRSA. MRSA was
      isolated from the wound in 17 of 30 amputations. More patients in the control
      group had a below knee amputation (38 of 54 compared with 12 of 30, p<0.02).
      Mortality in MRSA positive patients was higher than controls, (12 of 28, 43%,
      versus 4 of 44, 9%, p<0.01). Primary healing was achieved in only 4 of 17 (24%)
      amputations where MRSA was isolated from the wound. This compared with 31 of 54
      (57%) controls (p<0.05). Delayed healing due to chronic infection was also more
      likely in MRSA positive patients (p<0.01). CONCLUSION: In view of the high
      morbidity and mortality in patients with MRSA positive isolates specific
      antibiotic prophylaxis against MRSA should be considered in patients undergoing
      major amputation.

PMID- 11506514
TI  - The influence of intraarterial prostaglandin E(1) on vascular hydraulic impedance
      and infrainguinal graft patency.
AB  - OBJECTIVES: To evaluate the influence of intraoperative arterial prostaglandin
      E(1)(alprostadil) infusion on hydraulic impedance in relation to graft patency.
      METHODS: Hydraulic impedance was measured in 115 infrainguinal bypasses by means
      of the extracorporeal-bypass-flow method (EBF). Fifty-eight femoro-popliteal and
      57 femoro-crural polytetrafluoroethylene (PTFE) grafts were included. 10 microg
      of alprostadil were administered into a temporary bypass and the haemodynamic
      changes were recorded. The reactions of input (Z(x)) and characteristic (Z(0))
      impedances as well as phase relations were derived and related to graft outcome
      after three years. RESULTS: Significant changes after administration of
      prostaglandin were observed for overall pressure (74 vs. 84 mmHg, p<0.01), flow
      rate (194 vs 160 ml/min, p<0.01), input impedance (0.55 vs. 0.75 PRU, p<0.01) and
      the phase angle of the first harmonic (-18 degrees vs -26 degrees, p<0.01). An
      increase of at least one degree of the first harmonic phase angle following
      alprostadil injection in the crural bypass group was associated with a
      significant better graft prognosis of crural (p<0.01) but not popliteal grafts.
      Primary and secondary patency rates after three years for crural grafts with an
      increase of at least one degree were 62% and 63% (n=45) and for non-responders
      18% and 0% (n=12, p(prim)<0.01, p(sec)<0.001). All crural bypasses with poor
      prostaglandin reaction occluded within 9 months (n=12) after the operation.
      CONCLUSIONS: The EBF method allows a combined assessment of peripheral resistance
      and impedance parameters. The response of the first harmonic phase angle provides
      important predictive information regarding femoro-crural grafts.

PMID- 11506515
TI  - Dacron vs. polytetrafluoroethylene grafts for femoropopliteal bypass: a
      prospective randomised multicentre trial.
AB  - OBJECTIVES: To compare the patency of PTFE (Polytetrafluoroethylene) and unsealed
      knitted Dacron femoro-popliteal bypasses. DESIGN: Multi-centre prospective
      randomised trial. MATERIALS AND METHODS: Of 203 patients randomised, 194 were
      included in the final analysis (103 Dacron grafts and 91 PTFE grafts). The median
      follow-up was 36 months (range: 6-72 months); the distal anastomosis was above
      knee in 141 and below-knee in 53 cases. Univariate comparisons of patency were
      made by the Kaplan-Meier method, multivariate calculations on the effects of
      covariables by a Cox regression analysis. RESULTS: There was no difference
      regarding primary and secondary patency or limb salvage between Dacron and PTFE.
      The primary 3-year patency for Dacron grafts was 64% (95% confidence interval
      [C.I.] 55-74%) and for PTFE grafts 61% (C.I. 49-72%). The corresponding 3-year
      secondary patency was 81% (C.I. 73-89%) and 75% (C.I. 65-86%) respectively, the
      limb salvage rate 90% (C.I. 84-96%) and 91% (C.I. 84-97%). Upon multivariate
      analysis below-knee anastomosis was the principal independent predictor of
      primary graft failure (risk ratio 1.7 [C.I. 1.05-2.8]), impaired secondary
      patency was associated with infragenicular bypass (risk ratio 3.3 [C.I. 1.8-6.3])
      and distal gangrene (risk ratio [C.I. 1.01-3.8]p=0.048), major amputation was
      independently predicted by below-knee bypass, tissue necrosis, and poor run-off
      index. CONCLUSIONS: PTFE and Dacron are equally suitable for femoro-popliteal
      bypass.

PMID- 11506516
TI  - Low arginine plasma levels do not aggravate renal blood flow after experimental
      renal ischaemia/reperfusion.
AB  - BACKGROUND: Ischaemic renal dysfunction is present in many clinical settings,
      including cardiovascular surgery. Renal hypoperfusion seems to be the most
      important pathophysiologic mechanism. Arginine plasma levels are rate limiting
      for NO synthesis, and low arginine plasma levels are seen after major vascular
      surgery. OBJECTIVE: to establish the effects of low arginine plasma levels on
      renal blood flow after renal ischaemia/reperfusion. DESIGN: Wistar rats were used
      in this unilateral renal ischaemia/reperfusion model. After 70 min of ischaemia,
      the kidney was reperfused for 150 min. Arginase infusion was used to lower
      arginine plasma levels. Blood flow measurement was performed at the end of the
      experiment using radiolabelled microspheres. Additional experiments were
      performed for histopathology. RESULTS: Arginase efficiently decreased arginine
      plasma levels to about 50% of normal. There was a lower blood flow in the
      ischaemic kidney than the contralateral (non-ischaemic) kidney. Lowering arginine
      plasma levels did not reduce renal blood flow in the ischaemic kidney. Renal
      histopathology was not influenced by lowered arginine plasma levels. CONCLUSIONS:
      Lowering arginine plasma levels did not affect blood flow or histology following
      renal ischaemia and reperfusion.

PMID- 11506517
TI  - Risk factors and operative results of patients aged less than 66 years operated
      on for asymptomatic abdominal aortic aneurysm.
AB  - OBJECTIVE: To report risk factors, early operative results and survival after
      repair of asymptomatic abdominal aortic aneurysm (AAA) in patients aged less than
      66 years. DESIGN: a retrospective study based on a prospectively updated database
      in a University hospital. PATIENTS AND METHODS: Between 1985 and 1999, 118
      patients of less than 66 years were operated for AAA. Pre-operative risk factors,
      early complications, operative mortality (<30 days), and survival are compared
      with that of 333 older patients operated during the same period. RESULTS: Risk
      factors were similar to older patients. Serious early (<30 days) complications
      were recorded in 20% of both groups. The operative mortality was 1.7% for the
      younger patients and 6% for the older (n.s.). The eight-year survival of the
      younger patients was 69%, which was significantly below that of a demographically
      matched population. The older patients had a significantly poorer eight-year
      survival of 47% (p<0.01), but their relative survival was significantly better
      (p<0.05). CONCLUSIONS: Younger patients with an AAA were not healthier than older
      patients. Complications were equally common among both groups. Although the
      operative mortality was lower, the long-term relative survival was poorer than
      that of the older patient. Present data do not support a more aggressive surgical
      attitude towards the younger patients with an asymptomatic abdominal aortic
      aneurysm, as compared to the older.

PMID- 11506518
TI  - The influence of homologous blood transfusion on immunity and clinical outcome in
      aortic surgery.
AB  - OBJECTIVES: To evaluate the influence of homologous blood transfusion on immune
      responses and post-operative morbidity in aortic surgery. DESIGN: Analysis of the
      effects of homologous blood transfusion in 128 patients in a prospective
      randomised trial evaluating homologous and autologous blood transfusion in aortic
      surgery. MATERIALS AND METHODS: Blood sampled before and at five times after
      surgery was assayed for C-reactive protein (CRP), neutrophil elastase, TNF-alpha
      and IL-6. Transfusions, morbidity and mortality were recorded; factors associated
      with poor outcome were identified by logistic regression. RESULTS: homologous
      transfusion during surgery was required in 32 patients and precipitated an
      increase in neutrophil elastase (p=0.008) and TNF-alpha (p=0.015) but not IL-6
      and CRP. Elastase peaked early in transfused patients at 41.27 (13.92-52.11)
      Deltang/ml by 2 h compared to a peak of 21.51 (10.64-31.13) Deltang/ml by 24 h in
      those who were not transfused. TNF-alpha peaked at 1.2 (0-4.33) Deltapg/ml by
      wound closure in transfused patients and at -0.1 (-2.05-2.52) Deltapg/ml by 2 h
      without transfusion. Intra-operative homologous transfusion was associated with
      increased mortality (p=0.01) and prolonged intensive care stay (p=0.03).
      Mortality increased with age (p=0.003) and was inversely related to the CRP peak
      (p=0.007). Prolonged surgery predicted post-operative complications (p=0.025).
      CONCLUSION: Homologous transfusion increased the inflammatory response to aortic
      surgery and was associated with mortality.

PMID- 11506519
TI  - Intraoperative, perioperative and late complications with endovascular therapy of
      aortic aneurysm.
AB  - PURPOSE: To describe the incidence and management of the intraoperative,
      perioperative and late complications of endovascular aortic aneurysm repair.
      METHODS: Endovascular aneurysm repair was attempted in 130 patients between
      October, 1995 and January, 2000. Follow-up including computed tomography (CT) was
      performed in the immediate postoperative period and then at 3, 6, 9 and 12 months
      and biannually thereafter. The median follow-up period was 20 months. RESULTS:
      Intra- and perioperative problems occurred in 26 patients (20%). Conversion to
      open surgery was required in five cases (4%). The primary technical success rate
      was 86%. Three patients (2%) died within the first 30 postoperative days. Late
      problems occurred in 28 patients (26%). These included: endoleaks (type I: 5%;
      type II: 10%; type III: 1%) and limb occlusion (3%). The cumulative rate of
      freedom from secondary intervention was in the first 65 patients treated: 86% and
      65% after 1 and 3 years, respectively, and in the last 65 patients: 90% at 1
      year. CONCLUSIONS: Endovascular aneurysm repair is associated with a higher
      complication rate than open surgery.

PMID- 11506520
TI  - Three year single centre experience with the AneuRx aortic stent graft.
AB  - OBJECTIVES: To report the mid-term single-centre experience with the AneuRx self
      expandable nitinol stentgraft for endovascular aneurysm repair. PATIENTS AND
      METHODS: Between December 1996 and January 2000 a total of 128 patients were
      treated with an AneuRx bifurcated stentgraft. Of these, 77 patients had a minimum
      follow-up of 12 months. Patient operative and follow-up data were prospectively
      gathered. RESULTS: Two (3%) conversions were necessary. Median hospital stay was
      3 days. One superficial wound infection occurred. Periprocedural (30 days)
      mortality was 5% (four patients). Three graft occlusions were noted of which two
      required treatment. Fifteen patients developed 18 endoleaks (six type 1, eight
      type 2 and four type 3). Type 1 and type 3 endoleaks were treated by extension
      cuffs. Four type 2 endoleaks were treated with embolisation or direct lumbar
      puncture. Two-year freedom from endoleak was 76%. Graft migration occurred in six
      cases, resulting in a 2-year freedom from migration of 90%, kinking only once.
      CONCLUSIONS: endovascular AAA treatment is feasible and so far mid-term results
      are without major problems. Extensive follow-up is essential as secondary
      problems may occur later. Long-term results are to be awaited.

PMID- 11506521
TI  - The association between co-morbidity and mortality after abdominal aortic
      aneurysm endografting in patients ineligible for elective open surgery.
AB  - OBJECTIVE: To investigate whether co-morbidity affects mortality after
      endovascular stenting in patients who are fit and unfit for open surgery.
      METHODS: Data were obtained from the EUROSTAR registry. The association between
      co-morbidity and mortality was examined by Cox proportional hazards models.
      RESULTS: Between 1994 and July 2000, 2862 patients underwent aneurysm stenting;
      381 were unfit for open surgery. The early/late mortality rates for patients fit
      for surgery, patients unfit for surgery and patients unfit for anaesthesia were
      2.7/5.2%, 5.1/11.4% (p=0.035/p<0.0001) and 3.7/11.0% (NS/p=0.016), respectively.
      The survival curves among patients with poor medical condition were significantly
      worse than in those patients with a good medical condition (p=0.001). The
      presence or absence of co-existing diseases did not affect the mortality rate in
      patients unfit for open surgery. The age-adjusted mortality risks of patients fit
      for open surgery and pulmonary disease or diabetes mellitus were 1.41 (1.02-1.95)
      and 1.75 (1.12-2.74), respectively. CONCLUSIONS: Patients with co-morbidity had a
      significantly higher mortality after aortic endografting compared with patients
      fit for open surgery. Co-morbidity did not increase mortality after endovascular
      abdominal repair in patients unfit for open surgery. Endovascular repair of
      abdominal aortic aneurysm seems to have a limited benefit in patients unfit for
      open surgery.

PMID- 11506522
TI  - Two-stage, delayed endovascular treatment of traumatic rupture of the thoracic
      aorta.

PMID- 11506523
TI  - Combined surgical and endovascular treatment of pseudoaneurysms of the visceral
      arteries and of the left iliac arteries after thoracoabdominal aortic surgery.

PMID- 11506524
TI  - Repair of ruptured giant renal artery aneurysm with kidney salvage.

PMID- 11506525
TI  - Surgical treatment of renal cell carcinoma in a horseshoe-shaped kidney
      concomitant with an aortic aneurysm.

PMID- 11506526
TI  - EUROVASC report 1999.

PMID- 11506528
TI  - Statistical analysis of hippocampal asymmetry in schizophrenia.
AB  - The asymmetry of brain structures has been studied in schizophrenia to better
      understand its underlying neurobiology. Brain regions of interest have previously
      been characterized by volumes, cross-sectional and surface areas, and lengths.
      Using high-dimensional brain mapping, we have developed a statistical method for
      analyzing patterns of left-right asymmetry of the human hippocampus taken from
      high-resolution MR scans. We introduce asymmetry measures that capture
      differences in the patterns of high-dimensional vector fields between the left
      and right hippocampus surfaces. In 15 pairs of subjects previously studied (J. G.
      Csernansky et al., 1998, Proc. Natl. Acad. Sci. USA 95, 11406-11411). we define
      the difference in hippocampal asymmetry patterns between the groups. Volume
      analysis indicated a large normative asymmetry between left and right hippocampus
      (R > L), and shape analysis allowed us to visualize the normative asymmetry
      pattern of the hippocampal surfaces. We observed that the right hippocampus was
      wider along its lateral side in both schizophrenia and control subjects. Also,
      while patterns of hippocampal asymmetry were generally similar in the
      schizophrenia and control groups, a principal component analysis based on left
      right asymmetry vector fields detected a statistically significant difference
      between the two groups, specifically related to the subiculum.

PMID- 11506529
TI  - Syntactic processing in left prefrontal cortex is independent of lexical meaning.
AB  - In language comprehension a syntactic representation is built up even when the
      input is semantically uninterpretable. We report data on brain activation during
      syntactic processing, from an experiment on the detection of grammatical errors
      in meaningless sentences. The experimental paradigm was such that the syntactic
      processing was distinguished from other cognitive and linguistic functions. The
      data reveal that in syntactic error detection an area of the left dorsolateral
      prefrontal cortex, adjacent to Broca's area, is specifically involved in the
      syntactic processing aspects, whereas other prefrontal areas subserve general
      error detection processes.

PMID- 11506530
TI  - An examination of the effects of stimulus type, encoding task, and functional
      connectivity on the role of right prefrontal cortex in recognition memory.
AB  - Right anterior prefrontal cortex and other brain areas are active during memory
      retrieval but the role of prefrontal cortex and how it interacts with these other
      regions to mediate memory function remain unclear. To explore these issues we
      used positron emission tomography to examine the effects of stimulus material and
      encoding task on brain activity during visual recognition, assessing both task
      related changes and functional connectivity. Words and pictures of objects were
      encoded using perceptual and semantic strategies, resulting in better memory for
      semantically encoded items. There was no significant effect of prior encoding
      strategy on brain activity during recognition. Right anterior prefrontal cortex
      was equally active during recognition of both types of stimuli irrespective of
      initial encoding strategy. Regions whose activity was positively correlated with
      activity in right anterior prefrontal cortex included widespread areas of
      prefrontal and inferior temporal cortices bilaterally. Activity in this entire
      network of regions was negatively correlated with recognition accuracy of
      semantically encoded items. These results suggest that initial encoding task has
      little impact on the set of brain regions that is active during subsequent
      recognition. Right anterior prefrontal cortex appears to be involved in retrieval
      mode, reflected in its equivalent activity across conditions differing in both
      stimulus type and encoding task, and also in retrieval effort, shown by the
      negative correlation between its functional connectivity and individual
      differences in recognition accuracy.

PMID- 11506531
TI  - Transperceptual encoding and retrieval processes in memory: a PET study of visual
      and haptic objects.
AB  - An important objective of functional neuroimaging research is to identify
      neuroanatomical correlates of memory processes such as encoding and retrieval. In
      typical studies directed at this goal, however, the to-be-remembered information
      has been presented in a single perceptual modality. Under these conditions it is
      not known whether the observed brain activity reflects the studied memory process
      as such or only the memory process in the given modality. The positron emission
      tomography (PET) study reported here was designed to identify brain regions
      involved in encoding and retrieval processes specific to visual and haptic
      modalities, as well as those common to the two modalities. These latter, common
      regions, were assumed to be associated with "transperceptual" encoding and
      retrieval processes. Abstract three-dimensional objects, difficult to describe
      verbally, served as to-be-remembered materials. A multivariate partial least
      squares analysis of the PET data revealed that transperceptual encoding processes
      activated right medial temporal lobe, superior prefrontal cortex bilaterally, and
      posterior inferior temporal gyrus bilaterally. Transperceptual recognition
      activations were observed in two right orbitofrontal regions and in anterior
      cingulate. These results provide initial evidence that some processes involved in
      memory encoding and retrieval operate beyond perceptual processes and in that
      sense are transperceptual.

PMID- 11506532
TI  - Language mapping in less than 15 minutes: real-time functional MRI during routine
      clinical investigation.
AB  - Neurosurgical interventions often require the presurgical determination of
      language dominance or mapping of language areas. Results obtained by fMRI are
      closely correlated with invasive procedures such as electrical stimulation
      mapping or the intracarotid amobarbital test. However, language fMRI is not used
      routinely, because postprocessing is time-consuming. We utilized a real-time
      analysis software installed directly on the MR console computer and SPM99 as
      reference postprocessing software. We assessed the reliability of the immediate
      determination of language dominance based on individual activation maps by
      comparing the results of the visual analysis of images derived from conventional
      postprocessing with those produced by the real-time tool. All images were rated
      independently by six senior neurologists blinded to other data. We validated the
      robustness of the real-time method statistically by comparing global and regional
      lateralization indices derived from real-time and postprocessing analysis.
      Functional MRI was performed with a standard 1.5-T whole-body scanner. Brain
      activity was contrasted between an alternating semantic judgment and letter
      matching task. Twelve right-handed, healthy control subjects and 12 consecutive
      patients with drug-resistant, localization-related epilepsy were investigated.
      The semantic condition induced almost invariably left hemispheric activations in
      Broca's area, the premotor cortex, the dorsolateral prefrontal cortex, and the
      temporoparietal region. Although real-time analysis reduced noise less
      effectively than SPM99, visual ratings and lateralization indices produced highly
      concordant results with both methods. In conclusion, real-time fMRI, as used
      here, allowed reliable language lateralization and mapping in less than 15 min
      during routine clinical MRI investigation with no need for postprocessing.

PMID- 11506533
TI  - A unified statistical approach to deformation-based morphometry.
AB  - We present a unified statistical framework for analyzing temporally varying brain
      morphology using the 3D displacement vector field from a nonlinear deformation
      required to register a subject's brain to an atlas brain. The unification comes
      from a single model for structural change, rather than two separate models, one
      for displacement and one for volume changes. The displacement velocity field
      rather than the displacement itself is used to set up a linear model to account
      for temporal variations. By introducing the rate of the Jacobian change of the
      deformation, the local volume change at each voxel can be computed and used to
      measure possible brain tissue growth or loss. We have applied this method to
      detecting regions of a morphological change in a group of children and
      adolescents. Using structural magnetic resonance images for 28 children and
      adolescents taken at different time intervals, we demonstrate how this method
      works.

PMID- 11506534
TI  - Memory traces for words as revealed by the mismatch negativity.
AB  - Brain responses to the same spoken syllable completing a Finnish word or a pseudo
      word were studied. Native Finnish-speaking subjects were instructed to ignore the
      sound stimuli and watch a silent movie while the mismatch negativity (MMN), an
      automatic index of experience-dependent auditory memory traces, was recorded. The
      MMN to each syllable was larger when it completed a word than when it completed a
      pseudo-word. This enhancement, reaching its maximum amplitude at about 150 ms
      after the word's recognition point, did not occur in foreign subjects who did not
      know any Finnish. These results provide the first demonstration of the presence
      of memory traces for individual spoken words in the human brain. Using whole-head
      magnetoencephalography, the major intracranial source of this word-related MMN
      was found in the left superior temporal lobe.

PMID- 11506535
TI  - Human somatosensory area 2: observer-independent cytoarchitectonic mapping,
      interindividual variability, and population map.
AB  - We analyzed the topographical variability of human somatosensory area 2 in 10
      postmortem brains. The brains were serially sectioned at 20 microm, and sections
      were stained for cell bodies. Area 2 was delineated with an observer-independent
      technique based on significant differences in the laminar densities of cell
      bodies. The sections were corrected with an MR scan of the same brain obtained
      before histological processing. Each brain's histological volume and
      representation of area 2 was subsequently reconstructed in 3-D. We found that the
      borders of area 2 are topographically variable. The rostral border lies between
      the convexity of the postcentral gyrus and some millimeters deep in the rostral
      wall of the postcentral sulcus. The caudal border lies between the fundus of the
      postcentral sulcus and some millimeters above it in the rostral wall. In contrast
      to Brodmann's map, area 2 does not extend onto the mesial cortical surface or
      into the intraparietal sulcus. When the postcentral sulcus is interrupted by a
      gyral bridge, area 2 crosses this bridge and is not separated into two segments.
      After cytoarchitectonic analysis, the histological volumes were warped to the
      reference brain of a computerized atlas and superimposed. A population map was
      generated in 3-D space, which describes how many brains have a representation of
      area 2 in a particular voxel. This microstructurally defined population map can
      be used to demonstrate activations of area 2 in functional imaging studies and
      therefore help to further understand the role of area 2 in somatosensory
      processing.

PMID- 11506536
TI  - Asymmetrical activation of human visual cortex demonstrated by functional MRI
      with monocular stimulation.
AB  - We have demonstrated asymmetric activation patterns in the visual cortices of
      normal humans who have undergone functional MRI with monocular photic
      stimulation. The contralateral hemisphere is activated more strongly and to a
      greater spatial extent than the ipsilateral hemisphere when either eye is
      stimulated. This asymmetry can be explained by nasotemporal asymmetries which
      have been described in anatomical studies of the visual system in primates and
      humans. In part, the representation of the monocular crescent of the temporal
      hemifield of either eye, which exists only in the crossed projection, may explain
      this. In addition, within the binocular field, there is a biased crossed
      projection of nasal retinal ganglion cells which drive the contralateral ocular
      dominance columns in V1. Finally, the blind spot representation in the
      ipsilateral visual cortex may also contribute to the observed asymmetries. Our
      study may in effect provide a functional correlate of the anatomical asymmetries
      that have been observed in humans and animals.

PMID- 11506537
TI  - Effect of respiratory CO(2) changes on the temporal dynamics of the hemodynamic
      response in functional MR imaging.
AB  - Increasing end-expiratory CO(2) levels (PETCO(2)) increases the dispersion and
      the time of maximum of the hemodynamic response curve in human primary visual
      cortex. This was demonstrated using event-related multislice functional magnetic
      resonance imaging (fMRI) with short repetition time and 3-s flicker light
      stimulation. Measurements were performed at 5 different PETCO(2) levels between
      20 and 60 mmHg using hyperventilation or by adding CO(2) to the inspired air.
      Between 30 and 60 mmHg the full-width-at-half-maximum of the hemodynamic response
      curve induced by visual stimulation increased nearly linearly at 130 ms per mmHg
      PETCO(2). Consistent with previous studies a concomitant decrease of the signal
      amplitude was observed at PETCO(2) values below 40 mmHg and above 50 mmHg. The
      relevance of these findings for the temporal resolution of fMRI and especially of
      event-related methods is discussed.

PMID- 11506538
TI  - Working memory in another dimension: functional imaging of human olfactory
      working memory.
AB  - The majority of working memory research has been carried out within the visual
      and auditory modalities, leaving it unclear how other modalities would map onto
      currently proposed working memory models. In this study we examined the
      previously uninvestigated area of olfactory working memory. Our aim was to
      investigate if olfactory working memory would engage prefrontal regions known to
      be involved in working memory for other sensory modalities. Using positron
      emission tomography we measured cerebral blood flow changes in 12 volunteers
      during an olfactory working memory task and a comparison visual working memory
      task. Our findings indicate that both olfactory and face working memory engaged
      dorsolateral and ventrolateral frontal cortex when the task requirements were
      matched; a conjunction analysis indicated overlap in the distribution of activity
      in the two tasks. Similarities and differences in activity were noted in parietal
      lobe regions, with both tasks engaging inferior areas of 40/7, but only visual
      working memory showing increased activity within left superior parietal cortex.
      The findings support the idea that working memory processes engage frontal
      cortical areas independent of the modality of input, but do not rule out the
      possibility of modality-specific neural populations within dorsolateral or
      ventrolateral cortex.

PMID- 11506539
TI  - Functional specificity of superior parietal mediation of spatial shifting.
AB  - Using event-related functional magnetic resonance imaging (fMRI) we determined
      how brain activity changes when an attended target shifts its location. In the
      main experiment, a white square could appear at 10 possible eccentricities along
      the horizontal meridian. It remained on the screen for a variable period of time
      and then changed location. At any time the stimulus could dim briefly. Subjects
      had to press a button when the stimulus dimmed. In order to perform this task
      attention had to be locked onto the target and shift with it. Half of the runs
      were performed overtly and half covertly. The event of interest consisted of the
      shift in the location of the attentional target. The state of maintained
      attention occurring in between the shifts constituted the baseline. The superior
      parietal gyrus was activated bilaterally in response to attentional shifts. No
      other area showed a significant response to shifting. On the left side the
      amplitude of the superior parietal response correlated positively with the
      distance of the shift. On the right side a significant correlation was present
      only for overt shifts. In a separate experiment we compared the maintaining of
      attention at a single spatial location to passive fixation: the frontal eye
      fields, anterior cingulate, right dorsolateral prefrontal cortex, and inferior
      parietal lobule were significantly activated, indicating that the absence of a
      shift-related response in these areas in the main experiment was due to the fact
      that they were equally activated by maintaining and shifting attention. The
      response to spatial shifts and the correlation with the distance between the
      original and the new location points to a specific role of the superior parietal
      gyrus in shifting the locus of spatial attention.

PMID- 11506541
TI  - Cerebral asymmetry and the effects of sex and handedness on brain structure: a
      voxel-based morphometric analysis of 465 normal adult human brains.
AB  - We used voxel-based morphometry (VBM) to examine human brain asymmetry and the
      effects of sex and handedness on brain structure in 465 normal adults. We
      observed significant asymmetry of cerebral grey and white matter in the
      occipital, frontal, and temporal lobes (petalia), including Heschl's gyrus,
      planum temporale (PT) and the hippocampal formation. Males demonstrated increased
      leftward asymmetry within Heschl's gyrus and PT compared to females. There was no
      significant interaction between asymmetry and handedness and no main effect of
      handedness. There was a significant main effect of sex on brain morphology, even
      after accounting for the larger global volumes of grey and white matter in males.
      Females had increased grey matter volume adjacent to the depths of both central
      sulci and the left superior temporal sulcus, in right Heschl's gyrus and PT, in
      right inferior frontal and frontomarginal gyri and in the cingulate gyrus.
      Females had significantly increased grey matter concentration extensively and
      relatively symmetrically in the cortical mantle, parahippocampal gyri, and in the
      banks of the cingulate and calcarine sulci. Males had increased grey matter
      volume bilaterally in the mesial temporal lobes, entorhinal and perirhinal
      cortex, and in the anterior lobes of the cerebellum, but no regions of increased
      grey matter concentration.

PMID- 11506540
TI  - The role of the medial wall and its anatomical variations for bimanual antiphase
      and in-phase movements.
AB  - The medial wall of the frontal cortex is thought to play an important role for
      bimanual coordination. However, there is uncertainty regarding the exact
      neuroanatomical regions involved. We compared the activation patterns related to
      bimanual movements using functional magnetic resonance imaging in 12 healthy
      right-handed subjects, paying special attention to the anatomical variability of
      the frontal medial wall. The subjects performed unimanual right and left and
      bimanual antiphase and in-phase flexion and extension movements of the index
      finger. Activation of the right supplementary motor area (SMA) proper, right and
      left caudal cingulate motor area (CMA), and right and left premotor cortices was
      significantly stronger during bimanual antiphase than bimanual in-phase
      movements, indicating an important function of these areas with bimanual
      coordination. A frequent anatomical variation is the presence of the
      paracingulate sulcus (PCS), which might be an anatomical landmark to determine
      the location of activated areas. Seven subjects had a bilateral, three a
      unilateral right, and two a unilateral left PCS. Because the area around the PCS
      is functionally closer coupled to the CMA than to the SMA, activation found in
      the area around the PCS should be attributed to the CMA. With anatomical
      variations such as the presence of a PCS or a vertical branch of the cingulate
      sulcus, normalization and determination of the activation with the help of
      stereotaxic coordinates can cause an incorrect shift of CMA activation to the
      SMA. This might explain some of the discrepancies found in previous studies.

PMID- 11506542
TI  - Generation of rapid eye movements during paradoxical sleep in humans.
AB  - Although rapid eye movements (REMs) are a prominent feature of paradoxical sleep
      (PS), their origin and functional significance remain poorly understood in
      humans. In animals, including nonhuman primates, REMs during PS are closely
      related to the occurrence of the so-called PGO waves, i.e., prominent phasic
      activities recorded throughout the brain but predominantly and most easily in the
      pons (P), the lateral geniculate bodies (G), and the occipital cortex (O).
      Therefore, and because the evolution of species is parsimonious, a plausible
      hypothesis would be that during PS in humans, REMs are generated by mechanisms
      similar to PGO waves. Using positron emission tomography and iterative cerebral
      blood flow measurements by H(2)(15)O infusions, we predicted that the brain
      regions where the PGO waves are the most easily recorded in animals would be
      differentially more active in PS than in wakefulness, in relation with the
      density of the REM production [i.e., we looked for the condition (PS versus
      wakefulness) by performance (REM density) interaction]. Accordingly, we found a
      significant interaction effect in the right geniculate body and in the primary
      occipital cortex. The result supports the hypothesis of the existence of
      processes similar to PGO waves in humans, responsible for REM generation. The
      interest in the presence of PGO waves in humans is outstanding because the
      cellular processes involved in, or triggered by, PGO waves might favor brain
      plasticity during PS.

PMID- 11506543
TI  - Motion correction algorithms may create spurious brain activations in the absence
      of subject motion.
AB  - This paper describes several experiments that prove that standard motion
      correction methods may induce spurious activations in some motion-free fMRI
      studies. This artifact stems from the fact that activated areas behave like
      biasing outliers for the difference of square-based measures usually driving such
      registration methods. This effect is demonstrated first using a motion-free
      simulated time series including artificial activation-like signal changes.
      Several additional simulations explore the influence of activation amplitude and
      extent. The effect is finally highlighted on an actual time series obtained from
      a 3-T magnet. All the experiments are performed using four different realignment
      methods, which allows us to show that the problem may be overcome by methods
      based on a robust similarity measure like mutual information.

PMID- 11506544
TI  - Diffusion tensor imaging and axonal tracking in the human brainstem.
AB  - Diffusion tensor MRI was used to demonstrate in vivo anatomical mapping of
      brainstem axonal connections. It was possible to identify the corticospinal tract
      (CST), medial lemniscus, and the superior, medial, and inferior cerebellar
      peduncles. In addition, the cerebral peduncle could be subparcellated into
      component tracts, namely, the frontopontine tract, the CST, and the temporo
      /parieto-/occipitopontine tract. Anatomical landmarks and tracking thresholds
      were established for each fiber and, using these standards, reproducibility of
      automated tracking as assessed by intra- and interrater reliability was found to
      be high (kappa > 0.82). Reconstructed fibers corresponded well to existing
      anatomical knowledge, validating the tracking. Information on the location of
      individual tracts was coregistered with quantitative MRI maps to automatically
      measure MRI parameters on a tract-by-tract basis. The results reveal that each
      tract has a unique spatial signature in terms of water relaxation and diffusion
      anisotropy.

PMID- 11506545
TI  - Template images for nonhuman primate neuroimaging: 1. Baboon.
AB  - Coregistration of functional brain images across many subjects offers several
      experimental advantages and is widely used for studies in humans. Voxel-based
      coregistration methods require a high-quality 3-D template image, preferably one
      that corresponds to a published atlas. Template images are available for human,
      but we could not find an appropriate template for neuroimaging studies in baboon.
      Here we describe the formation of a T1-weighted structural MR template image and
      a PET blood flow template, derived from 9 and 7 baboons, respectively. Custom
      software aligns individual MR images to the MRI template; human supervision is
      needed only to initially estimate any gross rotational misalignment. In these
      aligned individual images, internal subcortical fiducial points correspond
      closely to a photomicrographic baboon atlas with an average error of 1.53 mm.
      Cortical test points showed a mean error of 1.99 mm compared to the mean location
      for each point. Alignment of individual PET blood flow images directly to the PET
      template was compared to a two-step alignment process via each subject's MR
      image. The two transformations were identical within 0.41 mm, 0.54 degrees, and
      1.0% (translation, rotation, and linear stretch; mean). These quantities provide
      a check on the validity of the alignment software as well as of the template
      images. The baboon structural MR and blood flow PET templates are available on
      the Internet (purl.org/net/kbmd/b2k) and can be used as targets for any image
      registration software.

PMID- 11506546
TI  - Template images for nonhuman primate neuroimaging: 2. Macaque.
AB  - Neuroimaging studies are increasingly performed in macaque species, including the
      pig-tailed macaque (Macaca nemestrina). At times experimental questions can be
      answered by analysis of functional images in individual subjects and reference to
      a structural image in that subject. However, coregistration of functional brain
      images across many subjects offers the experimental advantage of enabling voxel
      based analysis over multiple subjects and is therefore widely used in human
      studies. Voxel-based coregistration methods require a high-quality 3D template
      image. We created such templates, derived from T1-weighted MRI and blood-flow PET
      images from 12 nemestrina monkeys. We designed the macaque templates to be
      maximally compatible with the baboon template images described in a companion
      paper, to facilitate cross-species comparison of functional imaging data. Here we
      present data showing the reliability and validity of automatic image registration
      to the template. Alignment of selected internal fiducial points was accurate to
      within 1.9 mm overall (mean) even across species. The template images, along with
      copies aligned to the UCLA nemestrina brain atlas, are available on the Internet
      (purl.org/net/kbmd/n2k) and can be used as targets with any image registration
      software.

PMID- 11506547
TI  - Different brain correlates for watching real and virtual hand actions.
AB  - We investigated whether observation of actions reproduced in three-dimensional
      virtual reality would engage perceptual and visuomotor brain processes different
      from those induced by the observation of real hand actions. Participants were
      asked to passively observe grasping actions of geometrical objects made by a real
      hand or by hand reconstructions of different quality in 3D virtual reality as
      well as on a 2D TV screen. We found that only real actions in natural environment
      activated a visuospatial network including the right posterior parietal cortex.
      Observation of virtual-reality hand actions engaged prevalent visual perceptual
      processes within lateral and mesial occipital regions. Thus, only perception of
      actions in reality maps onto existing action representations, whereas virtual
      reality conditions do not access the full motor knowledge available to the
      central nervous system.

PMID- 11506548
TI  - Interaction of tactile input in the human primary and secondary somatosensory
      cortex--a magnetoencephalographic study.
AB  - Interaction of simultaneous tactile input at two finger sites in primary (SI) and
      secondary somatosensory cortex (SII) was studied by whole-head
      magnetoencephalography. Short pressure pulses were delivered to fingers of the
      right and left hand at an interstimulus interval of 1.6 s. The first phalanx of
      the left digit 1 and four other sites were stimulated either separately or
      simultaneously. We compared four sites with increasing distance: the second
      phalanx of left digit 1, left digit 5, and digits 1 and 5 of the right hand. The
      temporal evolution of source activity in the contralateral SI and bilateral SII
      was calculated using spatiotemporal source analysis. Interaction was assessed by
      comparing the source activity during simultaneous stimulation with the sum of the
      source activities elicited by separate stimulation. Significant suppressive
      interaction was observed in contralateral SI only for stimuli at the same hand,
      decreasing with distance. In SII, all digits of the same and the opposite hand
      interacted significantly with left digit 1. When stimulating bilaterally, SII
      source waveforms closely resembled the time course of the response to separate
      stimulation of the opposite hand. Thus, in bilateral simultaneous stimulation,
      the contralateral input arriving first in SII appeared to inhibit the later
      ipsilateral input. Similarly, the separate response to input at two unilateral
      finger sites which arrived slightly earlier in SII dominated the simultaneous
      response. Our results confirm previous findings of considerable overlap in the
      cortical hand representation in SII and illustrate hemispheric specialization to
      contralateral input when simultaneous stimuli occur bilaterally.

PMID- 11506549
TI  - A reference effect approach for power analysis in fMRI.
AB  - In fMRI, the issues involved in the control of type I error are fairly well
      understood. In contrast, the control of type II error has received less formal
      attention. This is perhaps due to the fact that the consideration of type II
      error requires the specification of an alternative hypothesis/experimental
      effect. In this paper, we present a method for expressing experimental effects in
      fMRI in a manner relative to a reference effect. A reference effect is chosen
      based on its neurophysiological significance to the researcher. This method
      provides a means to quantitatively express alternative hypotheses for fMRI, thus
      allowing type II error assessment prior to the collection of fMRI data. The
      simultaneous control of both type I and type II error should make meaningful
      interpretations possible from both positive and negative fMRI results.

PMID- 11506550
TI  - Event-related fMRI with simultaneous and continuous EEG: description of the
      method and initial case report.
AB  - We report on the initial imaging findings with a new technique for the
      simultaneous and continuous acquisition of functional MRI data and EEG recording.
      Thirty-seven stereotyped interictal epileptiform discharges (spikes) were
      identified on EEG recorded continuously during the fMRI acquisition on a patient
      with epilepsy. Localization of the BOLD activation associated with the EEG events
      was consistent with previous findings and EEG source modeling. The time course of
      activation was comparable with the physiological hemodynamic response function
      (HRF). The new methodology could lead to novel and important applications in many
      areas of neuroscience.

PMID- 11506551
TI  - Interconversion of (S)-glutamate and (2S,3S)-3-methylaspartate: a distinctive
      B(12)-dependent carbon-skeleton rearrangement.
AB  - The interconversion of (S)-glutamate and (2S,3S)-3-methylaspartate catalyzed by
      B(12)-dependent glutamate mutase is discussed using results from high-level ab
      initio molecular orbital calculations. Evidence is presented regarding the
      possible role of coenzyme-B(12) in substrate activation and product formation via
      radical generation. Calculated electron paramagnetic resonance parameters support
      experimental evidence for the involvement of substrate-derived radicals and will
      hopefully aid the future detection of other important radical intermediates. The
      height of the rearrangement barrier for a fragmentation-recombination pathway,
      calculated with a model that includes neutral amino and carboxylic acid
      substituents in the migrating glycyl group, supports recent experimental evidence
      for the interconversion of (S)-glutamate and (2S,3S)-3-methylaspartate through
      such a pathway. Our calculations suggest that the enzyme may facilitate the
      rearrangement of (S)-glutamate through (partial) proton-transfer processes that
      control the protonation state of substituents in the migrating group.

PMID- 11506552
TI  - Synthesis, characterization, and catalysis of mixed-ligand lithium aggregates,
      excellent initiators for the ring-opening polymerization of L-lactide.
AB  - Three novel mixed-ligand lithium aggregates, [(mu(3)-EDBP)Li(2)](2)[(mu(3)
      (n)Bu)Li(0.5Et(2)O)](2) (1), [(mu(3)-EDBP)Li(2)](2)[(mu(3)-OBn)Li](2) (2), and
      [(mu(3)-EDBP)Li(2)](2)[(mu(3)-OCH(2)CH(2)OCH(2)CH(3))Li](2) (3), have been
      synthesized and structurally characterized. The reaction of 2,2'-ethylidene
      bis(4,6-di-tert-butylphenol) (EDBP-H(2)) with 3.6 molar equiv of (n)BuLi gives 1
      in high yield. 1 further reacts with benzyl alcohol and 2-ethoxyethanol
      respectively to yield the corresponding products 2 and 3. Experimental results
      show that 2 and 3 efficiently initiate the ring-opening polymerization of L
      lactide in a controlled fashion, yielding polymers with very narrow
      polydispersity indexes in a wide range of monomer-to-initiator ratios.

PMID- 11506553
TI  - Self-assembly of folded m-phenylene ethynylene oligomers into helical columns.
AB  - Circular dichroism spectroscopy has been used to study the self-assembly of two
      series of m-phenylene ethynylene oligomers in highly polar solvents. The helical
      conformation of shorter oligomer lengths was found to be stabilized in aqueous
      acetonitrile solutions, while longer oligomers began to interact
      intermolecularly. The intermolecular aggregation of the oligomers in aqueous
      solutions revealed a chain length dependent association that required the
      presence of a stable helical conformation. Evidence for intermolecular
      interactions is provided by Sergeants and Soldiers experiments in which the twist
      sense bias of a chiral oligomer is transferred to an achiral oligomer.

PMID- 11506554
TI  - Photobleaching of asymmetric cyanines used for fluorescence imaging of single DNA
      molecules.
AB  - The photobleaching of the cyanine dyes YO and YOYO has been investigated for both
      free and DNA-bound dyes, using absorption and fluorescence spectroscopy coupled
      with fluorescence microscopy. For the free dyes, the nature of the reactive
      species involved in the photodegradation process is different for the monomer and
      the dimer, as shown by scavenger studies. For DNA-bound dyes, photoinduced fading
      of the visible absorption band occurs by different pathways depending on the drug
      binding mode and can be attenuated by appropriate scavengers. However, none of
      these scavengers were found to have any significant effect on the photobleaching
      of dye fluorescence. It appears that the reduction of fluorescence intensity
      comes from a quenching of the dye fluorescence by modified DNA bases, possibly 8
      oxo-7,8-dihydro-2'-deoxyguanosine.

PMID- 11506555
TI  - Palladium-catalyzed alpha-arylation of esters.
AB  - A new and simple one-pot procedure for the palladium-catalyzed intermolecular
      alpha-arylation of esters is described. A number of esters can be functionalized
      with a wide range of aryl bromides using Pd(OAc)(2) or Pd(2)(dba)(3) and bulky
      electron-rich o-biphenyl phosphines 1-3. Under the reaction conditions, using
      LiHMDS as base, alpha-arylation proceeds at room temperature or at 80 degrees C
      with very good yields and high selectivities for monoarylation. Important
      nonsteroidal antiinflammatory drug derivatives such as (+/-)-naproxen tert-butyl
      ester and (+/-)-flurbiprofen tert-butyl ester can be prepared in 79% and 86%
      yield, respectively. The catalyst system based on the di-tert-butylphosphine (2)
      is also active for the alpha-arylation of esters using aryl chlorides.
      Furthermore, using (3) the alpha-arylation of trisubstituted ester enolates can
      be accomplished to provide compounds that have quaternary centers.

PMID- 11506556
TI  - Biogenetically inspired approach to the Strychnos alkaloids. Concise syntheses of
      (+/-)-akuammicine and (+/-)-strychnine.
AB  - A linear synthesis of the indole alkaloid (+/-)-akuammicine (2) was completed by
      a novel sequence of reactions requiring only 10 steps from commercially available
      starting materials. The approach features a tandem vinylogous Mannich addition
      and an intramolecular hetero Diels-Alder reaction to rapidly assemble the
      pentacyclic heteroyohimboid derivative 8 from the readily available
      hydrocarboline 6. Oxidation of the E ring of 8 gave the lactone 9 that was
      converted into deformylgeissoschizine (11). The subsequent elaboration of 11 into
      2 was effected by a biomimetically patterned transformation that involved
      sequential oxidation and base-induced skeletal reorganization. A variation of
      these tactics was then applied to the synthesis of the C(18) hydroxylated
      akuammicine derivative 36. Because 36 had previously been converted into
      strychnine (1) in four steps, its preparation constitutes a concise, formal
      synthesis of this complex alkaloid.

PMID- 11506557
TI  - Reactions of tetrakis(dimethylamide)-titanium, -zirconium and -hafnium with
      silanes: synthesis of unusual amide hydride complexes and mechanistic studies of
      titanium-silicon-nitride (Ti-Si-N) formation.
AB  - M(NMe(2))(4) (M = Ti, Zr, Hf) were found to react with H(2)SiR'Ph (R' = H, Me,
      Ph) to yield H(2), aminosilanes, and black solids. Unusual amide hydride
      complexes [(Me(2)N)(3)M(mu-H)(mu-NMe(2))(2)](2)M (M = Zr, 1; Hf, 2) were observed
      to be intermediates and characterized by single-crystal X-ray diffraction.
      [(Me(2)N)(3)M(mu-D)(mu-NMe(2))(2)](2)M (1-d(2), 2-d(2)) were prepared through
      reactions of M(NMe(2))(4) with D(2)SiPh(2). Reactions of
      (Me(2)N)(3)ZrSi(SiMe(3))(3) (5) with H(2)SiR'Ph were found to give aminosilanes
      and (Me(2)N)(2)Zr(H)Si(SiMe(3))(3) (6). These reactions are reversible through
      unusual equilibria such as (Me(2)N)(3)ZrSi(SiMe(3))(3) (5) + H(2)SiPh(2) right
      arrow over left arrow (Me(2)N)(2)Zr(H)Si(SiMe(3))(3) (6) + HSi(NMe(2))Ph(2). The
      deuteride ligand in (Me(2)N)(2)Zr(D)Si(SiMe(3))(3) (6-d(1)) undergoes H-D
      exchange with H(2)SiR'Ph (R' = Me, H) to give 6 and HDSiR'Ph. The reaction of
      Ti(NMe(2))(4) with SiH(4) in chemical vapor deposition at 450 degrees C yielded
      thin Ti-Si-N ternary films containing TiN and Si(3)N(4). Ti(NMe(2))(4) reacts
      with SiH(4) at 23 degrees C to give H(2), HSi(NMe(2))(3), and a black solid.
      HNMe(2) was not detected in this reaction. The reaction mixture, upon heating,
      gave TiN and Si(3)N(4) powders. Analyses and reactivities of the black solid
      revealed that it contained -H and unreacted -NMe(2) ligands but no silicon
      containing ligand. Ab initio quantum chemical calculations of the reactions of
      Ti(NR(2))(4) (R = Me, H) with SiH(4) indicated that the formation of aminosilanes
      and HTi(NR(2))(3) was favored. These calculations also showed that HTi(NH(2))(3)
      (3b) reacted with SiH(4) or H(3)Si-NH(2) in the following step to give
      H(2)Ti(NH(2))(2) (4b) and aminosilanes. The results in the current studies
      indicated that the role of SiH(4) in its reaction with Ti(NMe(2))(4) was mainly
      to remove amide ligands as HSi(NMe(2))(3). The removal of amide ligands is
      incomplete, and the reaction thus yielded "=Ti(H)(NMe(2))" as the black solid.
      Subsequent heating of the black solid and HSi(NMe(2))(3) may then yield TiN and
      Si(3)N(4), respectively, as the Ti-Si-N materials.

PMID- 11506558
TI  - Expanded Prussian blue analogues incorporating [Re6Se8(CN)6](3-/4-) clusters:
      adjusting porosity via charge balance.
AB  - Face-capped octahedral [Re(6)Se(8)(CN)(6)](3-/4-) clusters are used in place of
      octahedral [M(CN)(6)](3-/4-) complexes for the synthesis of microporous Prussian
      blue type solids with adjustable porosity. The reaction between
      [Fe(H(2)O)(6)](3+) and [Re(6)Se(8)(CN)(6)](4-) in aqueous solution yields, upon
      heating, Fe(4)[Re(6)Se(8)(CN)(6)](3).36H(2)O (4). A single-crystal X-ray analysis
      confirms the structure of 4 to be a direct expansion of Prussian blue
      (Fe(4)[Fe(CN)(6)](3).14H(2)O), with [Re(6)Se(8)(CN)(6)](4-) clusters connected
      through octahedral Fe(3+) ions in a cubic three-dimensional framework. As in
      Prussian blue, one out of every four hexacyanide units is missing from the
      structure, creating sizable, water-filled cavities within the neutral framework.
      Oxidation of (Bu(4)N)(4)[Re(6)Se(8)(CN)(6)] (1) with iodine in methanol produces
      (Bu(4)N)(3)[Re(6)Se(8)(CN)(6)] (2), which is then metathesized to give the water
      soluble salt Na(3)[Re(6)Se(8)(CN)(6)] (3). Reaction of [Co(H(2)O)(6)](2+) or
      [Ni(H(2)O)(6)](2+) with 3 in aqueous solution affords
      Co(3)[Re(6)Se(8)(CN)(6)](2).25H(2)O (5) or Ni(3)[Re(6)Se(8)(CN)(6)](2).33H(2)O
      (6). Powder X-ray diffraction data show these compounds to adopt structures based
      on the same cubic framework present in 4, but with one out of every three cluster
      hexacyanide units missing as a consequence of charge balance. In contrast,
      reaction of [Ga(H(2)O)(6)](3+) with 3 gives Ga[Re(6)Se(8)(CN)(6)].6H(2)O (7),
      wherein charge balance dictates a fully occupied cubic framework enclosing much
      smaller cavities. The expanded Prussian blue analogues 4-7 can be fully
      dehydrated, and retain their crystallinity with extended heating at 250 degrees
      C. Consistent with the trend in the frequency of framework vacancies, dinitrogen
      sorption isotherms show porosity to increase along the series of representative
      compounds 7, Ga(4)[Re(6)Se(8)(CN)(6)](3).38H(2)O, and 6. Furthermore, all of
      these phases display a significantly higher sorption capacity and surface area
      than observed in dehydrated Prussian blue. Despite incorporating paramagnetic
      [Re(6)Se(8)(CN)(6)](3-) clusters, no evidence for magnetic ordering in compound 6
      is apparent at temperatures down to 5 K. Reactions related to those employed in
      preparing compounds 4-6, but carried out at lower pH, produce the isostructural
      phases H[cis-M(H(2)O)(2)][Re(6)Se(8)(CN)(6)].2H(2)O (M = Fe (8), Co (9), Ni
      (10)). The crystal structure of 8 reveals a densely packed three-dimensional
      framework in which [Re(6)Se(8)(CN)(6)](4-) clusters are interlinked through a
      combination of protons and Fe(3+) ions.

PMID- 11506559
TI  - Synthesis of ferrocenethiols containing oligo(phenylenevinylene) bridges and
      their characterization on gold electrodes.
AB  - Ferrocene-terminated oligo(phenylenevinylene) (OPV) methyl thiols have been
      prepared by orthogonal coupling of phenylene monomers. Ethoxy substituents on the
      phenyl rings improve the solubility of OPV, enabling the synthesis of longer
      oligomers. Self-assembled monolayers containing a mixture of a ferrocene OPV
      methyl thiol and a diluent alkanethiol were deposited on gold. A cyclic
      voltammetric study of monolayers containing oligomers of the same length with and
      without ethoxy solubilizing groups reveals that both solubilized and
      unsolubilized oligomers form well-packed self-assembled monolayers. Changing the
      position of the solubilizing groups on an oligomer chain does not preclude
      packing of the oligomer in the monolayer. Conventional chronoamperometry, which
      can be used to measure rate constants up to approximately 10(4) s(-1), is too
      slow to measure the electron-transfer rate through these oligomers over distances
      up to 35 A. OPV bridges are expected to be highly conjugated unlike
      oligo(phenyleneethynylene) bridges, which may be only partially conjugated
      because of rotation of the phenyl rings about the ethynylene bonds. Because of
      its high conjugation, OPV may prove useful as a molecular wire.

PMID- 11506560
TI  - Solution structures and reactivities of the mixed aggregates derived from n
      butyllithium and vicinal amino alkoxides.
AB  - Low-temperature (6)Li, (13)C, and (15)N NMR spectroscopies reveal that mixtures
      of n-BuLi and (1R,2S)-R'(2)NCH(R)CH(Ph)OLi (ROLi; R = Ph or Me; R'(2)N =
      pyrrolidino or Me(2)N) in THF/pentane afford a (n-BuLi)(3)(ROLi) (3:1) mixed
      tetramer and a C(2)-symmetric (n-BuLi)(2)(ROLi)(2) (2:2) mixed tetramer depending
      on the proportions of the reactants. The corresponding (n-BuLi)(ROLi)(3) (1:3)
      mixed tetramer is not observed. ROLi-mediated additions of n-BuLi to benzaldehyde
      proceed with up to 21:1 enantiomeric ratios that depend on the n-BuLi/ROLi
      stoichiometries. The enantioselectivities are considered in light of a previously
      posited mechanism involving reaction via the C(2)-symmetric 2:2 mixed tetramer.

PMID- 11506561
TI  - Rotational motion in liquid water is anisotropic: a nuclear magnetic resonance
      and molecular dynamics simulation study.
AB  - Experimental NMR measurements of the deuterium and (17)O T(1) relaxation times in
      deuterium-enriched liquid water have been performed from 275 to 350 K. These
      relaxation times can yield rotational correlation times of appropriate molecule
      fixed unit vectors if the quadrupole coupling constants and asymmetry parameters
      are known. We determine the latter from ab initio studies of water clusters and
      experimental chemical shift measurements. We find that the rotational correlation
      time for the OD bond vector in D(2)(16)O varies from 5.8 ps at 275 K to 0.86 ps
      at 350 K, and that the rotational correlation time for the out-of-plane vector of
      dilute D(2)(17)O in D(2)(16)O varies from 4.4 ps at 275 K to 0.64 ps at 350 K.
      These results indicate that the rotational motion of water is anisotropic.
      Molecular dynamics simulations of liquid water are in good agreement with these
      experiments at the higher temperatures, but the simulation results are
      considerably faster than experiment at the lower temperatures.

PMID- 11506562
TI  - Paramagnetic NMR investigations of high-spin nickel(II) complexes. Controlled
      synthesis, structural, electronic, and magnetic properties of dinuclear vs.
      mononuclear species.
AB  - New dissymmetric tertiary amines (N(3)SR) with varying N/S donor sets have been
      synthesized to provide mono- and dinuclear complexes. Acetate ions are used to
      complete the octahedral coordination sphere around nickel(II) atom(s). The facile
      conversion of mononuclear to dinuclear systems can be controlled to produce
      either mono- or dinuclear complexes from the same ligand. The dinuclear complex
      a(BPh(4))(2) ([Ni(2)(N(3)SSN(3))(OAc)(2)](BPh(4))(2)) has been characterized in
      the solid state by X-ray diffraction techniques as solvate:
      a(BPh(4))(2).(1/2)[5(CH(3)OH).(CH(3)CN).(CH(3)CH(2)OH)]. The two Ni atoms are six
      coordinated and bridged by a disulfide group and two bidentate acetates. Magnetic
      susceptibility reveals a weak ferromagnetic exchange interaction between the two
      Ni atoms with J = 2.5(7) cm(-1). UV-vis studies suggest that the six-coordinated
      structure persists in solution. The (1)H NMR spectrum of a(BPh(4))(2) exhibits
      sharp significantly hyperfine shifted ligand signals. A complete assignment of
      resonances is accomplished by a combination of methods: 2D-COSY experiments,
      selective chemical substitution, and analysis of proton relaxation data. Proton
      isotropic hyperfine shifts are shown to originate mainly from contact
      interactions and to intrinsically contain a small J-magnetic coupling and/or zero
      field splitting contribution. A temperature dependence study of longitudinal
      relaxation times indicates that a very unusual paramagnetic Curie dipolar
      mechanism is the dominant relaxation pathway in these weakly ferromagnetically
      spin-coupled dinickel(II) centers. The mononuclear nickel(II) analogue exhibits
      extremely broader (1)H NMR signals and only partial analysis could be performed.
      These data are consistent with a shortening of electronic relaxation times in
      homodinuclear compounds with respect to the corresponding mononuclear species.

PMID- 11506563
TI  - Amine-chelated aryllithium reagents--structure and dynamics.
AB  - Multinuclear NMR studies of five-membered-ring amine chelated aryllithium
      reagents 2-lithio-N,N-dimethylbenzylamine (1), the diethylamine and
      diisopropylamino analogues (2, 3), and the o-methoxy analogue (4), isotopically
      enriched in (6)Li and (15)N, have provided a detailed picture of the solution
      structures in ethereal solvents (usually in mixtures of THF and dimethyl ether,
      ether, and 2,5-dimethyltetrahydrofuran). The effect of cosolvents such as TMEDA,
      PMDTA, and HMPA has also been determined. All compounds are strongly chelated,
      and the chelation is not disrupted by these cosolvents. Reagents 1, 2, and 3 are
      dimeric in solvents containing a large fraction of THF. Below -120 degrees C,
      three chelation isomers of the dimers are detectable by NMR spectroscopy: one (A)
      with both nitrogens coordinated to one lithium of the dimer, and two (B and C) in
      which each lithium bears one chelating group. Dynamic NMR studies have provided
      rates and activation energies for the interconversion of the 1-A, 1-B, and 1-C
      isomers. They interconvert either by simple ring rotation, which interconverts B
      and C, or by amine decoordination (probably associative, DeltaG(++)(-93) = 8.5
      kcal/mol), which can interconvert all of the isomers. The dimers of 1 are
      thermodynamically more stable than those of model systems such as phenyllithium,
      o-tolyllithium, or 2-isoamylphenyllithium (5, DeltaDeltaG > or = 3.3 kcal/mol).
      They are not detectably deaggregated by TMEDA or PMDTA, although HMPA causes
      partial deaggregation. The dimers are also more robust kinetically with rates of
      interaggregate exchange, measured by DNMR line shape analysis of the C-Li signal,
      orders of magnitude smaller than those of models (DeltaDeltaG(++) > or = 4.4
      kcal/mol). Similarly, the mixed dimer of 1 and phenyllithium, 13, is kinetically
      more stable than the phenyllithium dimer by >2.2 kcal/mol. X-ray crystal
      structures of the TMEDA solvate of 1-A and the THF solvate of 3-B showed them to
      be dimeric and chelated in the solid state as well. Compound 4, which has a
      methoxy group ortho to the C-Li group, differs from the others in being only
      partially dimeric in THF, presumably for steric reasons. This compound is fully
      deaggregated by 1 equiv of HMPA. Excess HMPA leads to the formation of ca. 15% of
      a triple ion (4-T) in which both nitrogens appear to be chelated to the central
      lithium.

PMID- 11506564
TI  - Solution NMR determination of the seating(s) of meso-nitro-etioheme-1 in
      myoglobin: implications for steric constraints to meso position access in heme
      degradation by coupled oxidation.
AB  - The highly stereoselective cleavage of hemin in myoglobin by coupled oxidation
      has been attributed to steric barriers that leave more space near the alpha- than
      the other meso-positions. The steric barriers near meso positions in myoglobin
      have been investigated by establishing the thermodynamics and dynamics of
      possible seatings in the pocket of horse myoglobin of a four-fold symmetric
      etioheme I modified with a bulky nitro group at a single meso position. The
      cyanomet complex of this reconstituted myoglobin exhibits three sets of (1)H NMR
      resonances that are linked dynamically and occur in approximate populations
      ratios of 0.82:0.10:0.08. Two dimensional (1)H NMR has been used to assign the
      hemin and heme pocket resonances in the major isomer in solution and to determine
      that the hemin is oriented with the nitro group at the canonical gamma-meso
      position of native hemin. The dominance of this isomer is attributed to the
      solvent exposure of this portion of the hemin which stabilizes the highly polar
      nitro group. Using a combination of magnetization transfer among methyl groups of
      the three isomers due to "hopping" of the hemin about its normal, the assigned
      resonances of an isoelectronic, bis-cyano complex of meso-nitro-etioheme I, and
      the known essentially constant rhombic perturbation of heme pocket sites on the
      hyperfine shifts of heme methyl (Kolczak, U.; Hauksson, J. B.; Davis, N. L.;
      Pande, U.; de Ropp, J. S.; Langry, K. C.; Smith, K. M.; LaMar, G. N. J. Am. Chem.
      Soc. 1999, 121, 835-843); the two minor isomers are shown to place their bulky
      nitro group at the canonical delta-meso (8%) and alpha-meso positions (10%). The
      comparable population of the isomers with nitro groups at the hydrophobic alpha-
      and delta-meso positions dictates that, while the static crystal structure finds
      more room near the alpha-meso position, the deformation at minimal energetic
      expense near the alpha- and delta-meso positions is comparable. These results
      argue that factors other than simple steric influences control the selectivity of
      the ring cleavage in myoglobin.

PMID- 11506566
TI  - Mechanism of a novel exchange process in alkali metal salts of 1,5
      dicyclooctatetraenylnaphthalene dianion.
AB  - A novel low-temperature intramolecular exchange was detected by (13)C NMR
      spectrometry in the Na(+) and K(+) salts of the title compound. The process
      causes the pairwise exchange in the dianion ring of C(2"), C(3"), and C(4") with
      C(8"), C(7"), and C(6"), respectively. The free energy of activation
      (DeltaG()(exch)) for the dipotassium salt (2(2-)/2K(+)) in THF-d(8) at 230 K is
      12.6 kcal mol(-1). Two key questions are addressed: (1) Why are these carbons
      anisochronous and (2) what is the mechanism of exchange? NMR data for 1
      cyclooctatetraenylnaphthalenedipotassium (3(2-)/2K(+)) as well as ab initio HF/3
      21G(++) calculations for 3, 3(2-), and 3(2-)/2K(+) indicate that the
      nonequivalence is due to both slow rotation across a barrier at which the
      naphthalene and COT(2)(-) rings are approximately coplanar and slow inversion of
      the neutral COT ring. This results in the noteworthy circumstance of
      diastereotopic carbons being observed in a molecule that does not possess either
      a stereogenic or a prostereogenic center. Comparison of DeltaG()(exch) and
      DeltaG(++)(BS) for 2(2-)/2K(+) with the corresponding values for 2(2-)/2Na(+) and
      2(2-)/2Li(+) and of DeltaG(++)(exch) with DeltaG(++) for ring inversion in 1,4
      dicyclooctatetraenylnaphthalene leads to the conclusion that COT(2-) ring
      rotation and COT ring inversion both contribute to exchange in 2(2-)/2K(+) in a
      3:1 ratio, but that exchange occurs exclusively by ring rotation in 2(2-)/2Li(+).
      The latter result is attributed to looser ion pairing in the dilithium (and
      disodium) salts.

PMID- 11506565
TI  - Flash photolytic generation of ortho-quinone methide in aqueous solution and
      study of its chemistry in that medium.
AB  - Flash photolysis of o-hydroxybenzyl alcohol, o-hydroxybenzyl p-cyanophenyl ether,
      and (o-hydroxybenzyl)trimethylammonium iodide in aqueous perchloric acid and
      sodium hydroxide solutions, and in acetic acid and biphosphate ion buffers,
      produced o-quinone methide as a short-lived transient species that underwent
      hydration back to benzyl alcohol in hydrogen-ion catalyzed (k(H+) = 8.4 x 10(5)
      M(-1) s(-1)) and hydroxide-ion catalyzed (k(HO)- = 3.0 x 10(4) M(-1) s(-1))
      reactions as well as an uncatalyzed (k(UC) = 2.6 x 10(2) s(-1)) process. The
      hydrogen-ion catalyzed reaction gave the solvent isotope effect k(H+)/k(D)+ =
      0.42, whose inverse nature indicates that this process occurs by rapid and
      reversible equilibrium protonation of the carbonyl oxygen atom of the quinone
      methide, followed by rate-determining capture of the carbocation so produced by
      water. The magnitude of the rate constant of the uncatalyzed reaction, on the
      other hand, indicates that this process occurs by simple nucleophilic addition of
      water to the methylene group of the quinone methide. Decay of the quinone methide
      is also accelerated by acetic acid buffers through both acid- and base-catalyzed
      pathways, and quantitative analysis of the reaction products formed in these
      solutions shows that this acceleration is caused by nucleophilic reactions of
      acetate ion rather than by acetate ion assisted hydration. Bromide and
      thiocyanate ions also accelerate decay of the quinone methide through both
      hydrogen-ion catalyzed and uncatalyzed pathways, and the inverse nature of
      solvent isotope effects on the hydrogen-ion catalyzed reactions shows that these
      reactions also occur by rapid equilibrium protonation of the quinone methide
      carbonyl oxygen followed by rate-determining nucleophilic capture of the ensuing
      carbocation. Assignment of an encounter-controlled value to the rate constant for
      the rate-determining step of the thiocyanate reaction leads to pK(a) = -1.7 for
      the acidity constant of the carbonyl-protonated quinone methide.

PMID- 11506567
TI  - Polyphenylene dendrimers with different fluorescent chromophores asymmetrically
      distributed at the periphery.
AB  - A new synthetic approach leading to asymmetrically substituted polyphenylene
      dendrimers is presented. Following this method, polyphenylene dendrimers
      decorated with an increasing number of chromophores at the periphery have been
      obtained up to the second generation. Especially the synthesis of a polyphenylene
      dendrimer bearing three donor chromophores and one acceptor chromophore has been
      realized. Intramolecular energy transfer within this molecule is demonstrated by
      applying absorption and fluorescence measurements.

PMID- 11506568
TI  - The 2-norbornyl cation via the fragmentations of exo- and endo-2
      norbornyloxychlorocarbenes: distinction without much difference.
AB  - exo- and endo-2-norbornyloxychlorocarbenes (7) were generated photochemically
      from the corresponding diazirines (6). Both carbenes fragmented to [2-norbornyl
      cation (carbon monoxide) chloride] ion pairs in MeCN or 1,2-dichloroethane
      solutions. Products included exo-norbornyl chloride (8), endo-norbornyl chloride
      (9), norbornene (10), and nortricyclene (11). Fragmentation activation energies
      were very low (< approximately 4 kcal/mol) and, as a result, the (laser flash
      photolytic) rate constants for fragmentation were essentially identical for exo-7
      and endo-7 ( approximately 5 x 10(5) s(-1) in MeCN). Due to chloride return
      within the ion pairs, product distributions from exo- and endo-7 differed, with
      more endo-chloride formed from the endo-carbene: the 8/9 product ratio in MeCN
      was approximately 41 from exo-7, but only 4.6 from endo-7. Norbornene, formed by
      proton transfer to Cl(-) within the ion pairs, was a major product in both cases
      (44% from exo-7 and 62% from endo-7). In MeOH/MeCN, up to 28% of exo-2-norbornyl
      methyl ether formed at the expense of some of the norbornene, but even in 100%
      MeOH, the norbornyl chloride products of ion pair return still accounted for 46%
      and 31% of the exo-7 and endo-7 product mixtures (accompanied by 26-32% of
      norbornene). Electronic structure calculations on the ground states and
      fragmentation transition states of exo-7 and endo-7 are presented.

PMID- 11506569
TI  - Amine-promoted disproportionation and redistribution of trichlorosilane:
      formation of tetradecachlorocyclohexasilane dianion.

PMID- 11506570
TI  - Three-dimensional self-assembly of complex, millimeter-scale structures through
      capillary bonding.

PMID- 11506571
TI  - High activity enzyme microcrystal multilayer films.

PMID- 11506572
TI  - Synthesis and structures of novel low-valent group 14 1,3-dimetallacyclobutanes
      and a mixed-metal 1,3-stanna-plumbacyclobutane.

PMID- 11506574
TI  - (57)Fe Mossbauer investigation on doped nickelates ANiO(3) (A = Y, Lu, Tl).

PMID- 11506573
TI  - A bioinspired dicopper(II) catalyst for the transesterification of dimethyl
      phosphate.

PMID- 11506575
TI  - Energetics: a new field of applications for hydrophobic zeolites.

PMID- 11506576
TI  - Chromium(III)-promoted C(2) isotopic H-exchange in coordinated N-methylimidazole:
      exceptionally rapid or slow and normal?

PMID- 11506577
TI  - Resolution of (129)Xe chemical shifts at ultralow magnetic field.

PMID- 11506578
TI  - Relative orientation of quadrupole tensors from two-dimensional multiple-quantum
      MAS NMR.

PMID- 11506579
TI  - The reactivity of molecules trapped within the SAPO-34 cavities in the methanol
      to-hydrocarbons reaction.

PMID- 11506580
TI  - Acyloxymethylzinc reagents: preparation, reactivity, and solid-state structure of
      this novel class of cyclopropanating reagents.

PMID- 11506581
TI  - Preparation and characterization of purified amyloid fibrils.

PMID- 11506582
TI  - O-protonation of a terminal nitrosyl group to form an eta(1)-hydroxylimido
      ligand.

PMID- 11506584
TI  - Evidence for chemisorbed molecular hydrogen in Fe-ZSM5 from inelastic neutron
      scattering.

PMID- 11506583
TI  - Synthesis and proinflammatory effects of peptidoglycan-derived neoglycopeptide
      polymers.

PMID- 11506585
TI  - Selective functionalization of amino acids in water: a synthetic method via
      catalytic C-H bond activation.

PMID- 11506586
TI  - Barcoded resins: a new concept for polymer-supported combinatorial library self
      deconvolution.

PMID- 11506587
TI  - Bifunctional molecular sieve catalysts for the benign ammoximation of
      cyclohexanone: one-step, solvent-free production of oxime and epsilon-caprolactam
      with a mixture of air and ammonia.

PMID- 11506589
TI  - Enforced stacking in crowded arenes.

PMID- 11506588
TI  - Accelerated discovery of synthetic transfection vectors: parallel synthesis and
      screening of a degradable polymer library.

PMID- 11506590
TI  - Switching of a macromolecular helicity for visual distinction of molecular
      recognition events.

PMID- 11506591
TI  - Effects of hydration on the electronic structure of an enzyme: implications for
      the catalytic function.

PMID- 11506593
TI  - Enantioselective synthesis of fluorinated alpha-amino acids and derivatives in
      combination with ring-closing metathesis: intramolecular pi-stacking interactions
      as a source of stereocontrol.
AB  - [reaction: see text]. Hydride reduction of C=N bonds stereocontrolled by
      intramolecular pi-stacking interactions of 1-naphthylsulfinyl and N-aryl groups,
      nonoxidative Pummerer rearrangement, and ring-closing metathesis are efficiently
      combined in a highly stereoselective entry to enantiomerically pure cyclic and
      acyclic fluorinated beta-amino alcohols and alpha-amino acid derivatives,
      respectively.

PMID- 11506594
TI  - Solid-phase synthesis of aspartic peptidase inhibitors: 3-alkoxy-4-aryl
      piperidines.
AB  - [reaction: see text]. The 3-alkoxy-4-aryl piperidines are non-peptide
      peptidomimetic inhibitors of several aspartic peptidases. The solid-phase
      functionalization of 3,4-disubstituted piperidine scaffolds using a traceless
      linker strategy is described. Synthesis of diverse analogues based on this
      scaffold provides the potential to generate selective inhibitors of this
      important class of peptidase.

PMID- 11506595
TI  - Application of Ugi reactions in synthesis of divalent neoglycoconjugates:
      evidence that the sugars are presented in restricted conformation.
AB  - [reaction: see text]. The Ugi reaction has been used to prepare divalent
      galactose derivatives. NMR analysis shows that a divalent neoglycoconjugate,
      where the glycopeptides are bridged by a terephthaloyl group, is an 83:17 mixture
      of two conformers; the amide groups of the major isomer have E-anti
      conformations. The spatial relationship and the relative orientation of the
      sugars are restricted, which may have consequences for the recognition of this
      and related structures in biological systems.

PMID- 11506596
TI  - Synthesis and liquid membrane transport properties of photolabile molecular clips
      based on dithiane-spiro-crown ethers.
AB  - [reaction: see text]. Synthesis of novel dithiane-spiro-crown ethers starting
      from 5,5-di(hydroxymethyl)-1,3-dithiane is developed. These compounds can be used
      as building blocks to assemble photolabile bis-crown ethers via addition to
      dicarbonyl-containing tethers, e.g., isophthalic aldehyde. It is found that
      unlike their mono-crown precursors such bidentate bis-crowns are capable of
      efficient liquid membrane transport of, for example, methyl viologen. The
      transport can be interrupted photochemically, providing a basis for developing
      smart light-responsive membranes.

PMID- 11506597
TI  - Cyclic hexapeptides with free carboxylate groups as new receptors for
      monosaccharides.
AB  - [structure: see text]. Cyclic hexapeptides composed of alternating L-proline and
      3-aminobenzoic acid subunits with substituents on the aromatic subunits that
      contain free carboxylate groups are able to bind monosaccharides in 4%
      CD3OD/CDCl3. The binding selectivity of these peptides depends on the structure
      of the substituents on the aromatic subunits.

PMID- 11506598
TI  - Convergent synthesis of fully functionalized ring C allocolchicinoids.
      Benzannulation approach.
AB  - [reaction: see text]. A novel convergent approach to fully functionalized ring C
      allocolchicinoids is developed which is based on the benzannulation reaction of
      Fischer carbene complexes with alkynes. The efficacy of this strategy was
      established with the conversion of bromide 1a (R1 = Me, R2 = H) to the biaryl
      phenol 3a (R = Me, R(L) = Pr, R(S) = H) via the carbene complex 2a. Bromide 1b
      (R1 = t-Bu, R2 = OMe) was then used for the analogous preparation of the
      diastereomeric allocolchicinoids 3b (R = Me, R(L) = Pr, R(S) = H).

PMID- 11506599
TI  - Synthesis of photo- and electroactive stilbenoid dendrimers carrying dibutylamino
      peripheral groups.
AB  - [structure: see text]. A novel convergent synthetic route for the preparation of
      functionalized and fluorescent stilbenoid dendrons built on the 1,3,5-benzene
      core and endowed with a periphery of dibutylamino groups has been developed. Long
      alkyl chains have been incorporated on the peripheral amino moieties to increase
      the solubility of the final products. Good donor ability of the new dendrimers
      has been observed by cyclic voltammetry measurements as a result of the presence
      of the peripheral dibutylaniline moieties.

PMID- 11506600
TI  - Catalytic asymmetric dihydroxylation using phenoxyethoxymethyl-polystyrene (PEM)
      based novel microencapsulated osmium tetroxide (PEM-MC OsO4).
AB  - [reaction: see text]. A phenoxyethoxymethyl-polystyrene (PEM)-based novel polymer
      supported osmium catalyst has been developed. The catalyst was readily prepared
      from PEM polymer based on a microencapsulation technique, and asymmetric
      dihydroxylation of olefins has been successfully performed using (DHQD)2PHAL as a
      chiral ligand and K3Fe(CN)6 as a cooxidant in H2O/acetone. The catalyst was
      recovered quantitatively by simple filtration and reused without loss of activity
      several times.

PMID- 11506601
TI  - Oxidative transformation of arylmethyl bromides and alcohols with a combination
      of mesoporous silica FSM-16 and alkali iodides under photoirradiation.
AB  - [reaction: see text]. A mesoporous silica FSM-16 was found to be a selective and
      recyclable promoter for the oxidative dehalogenation of arylmethyl bromides to
      provide the corresponding alcohols and for the oxidation of arylmethyl alcohols
      to provide the corresponding aldehydes with a combination of alkali iodides and
      solvents under photoirradiation conditions.

PMID- 11506602
TI  - A library approach to the generation of bisubstrate analogue sulfotransferase
      inhibitors.
AB  - [reaction: see text]. A library of potential bisubstrate analogue inhibitors (1)
      targeting sulfotransferase enzymes was generated by the chemoselective ligation
      of the PAPS mimic 2 with a panel of 447 aldehydes. Preliminary screening has
      identified compounds that inhibit estrogen sulfotransferase (EST), an enzyme
      relevant to breast cancer.

PMID- 11506603
TI  - Synthesis of the naphthalene portion of the rubromycins.
AB  - [reaction: see text]. A synthesis of a reduced version of the naphthazarin found
      in the rubromycin class of natural products is reported. The naphthalene ring
      system is formed via a Dotz reaction with a symmetrical alkyne. Differentiation
      between the C1' and C3' groups of the Dotz adduct is achieved by selective
      oxidation since the two methylene groups possess different oxidation potentials.

PMID- 11506604
TI  - Stereocontrolled construction of tetrahydrofurans and gamma-butyrolactones using
      organomolybdenum chemistry.
AB  - [reaction: see text]. Diastereoselective conversion of pi-allylmolybdenum complex
      aldehyde 1 to organometallic triol 4 and diols 5, 10, and 13 is described.
      Stereocontrolled demetalation of 4, 5, and 13 was accomplished, leading to
      hydroxylated tetrahydrofurans and gamma-butyrolactones, as single
      diastereoisomers.

PMID- 11506605
TI  - Diverse cyclization catalyzed by In(OTf)3 for the convergent assembly of
      substituted tetrahydrofurans and tetrahydropyrans.
AB  - [reaction: see text]. A novel In(OTf)3-catalyzed (3,5) oxonium-ene type
      cyclization for the facile construction of various multisubstituted
      tetrahydrofurans and tetrahydropyrans was successfully developed. Further
      mechanistic investigations unveiled an In(OTf)3-catalyzed skeletal reorganization
      of the tetrahydrofuran to its thermodynamic isomer under thermal conditions.

PMID- 11506606
TI  - A versatile synthesis of substituted benzimidazolium salts by an amination/ring
      closure sequence.
AB  - [reaction: see text]. A new method to produce benzimidazolium salts based on a
      successive Buchwald-Hartwig amination and ring closure is reported. A variety of
      different benzimidazolium salts can be prepared using this procedure. Amines that
      bear an alpha-chiral group undergo the reaction to furnish chiral benzimidazolium
      salts. The salts that lack a C2 substituent on the heterocycle are readily
      deprotonated to give nucleophilic carbenes.

PMID- 11506607
TI  - Stereoselective synthesis of pseudopeptide microbial agent AI-77-B.
AB  - [structure: see text]. An efficient and highly stereoselective synthesis of the
      gastroprotective natural product AI-77-B is described. The stereocenters of the
      hydroxy amino acid moiety were generated by an ester-derived titanium-enolate
      mediated syn-aldol reaction, a Curtius rearrangement, and application of
      Dondoni's aldehyde homologation. Condensation with the dihydroisocoumarin
      fragment and subsequent deprotecting transformations furnished optically active
      AI-77-B.

PMID- 11506608
TI  - Thermally responsive dendrons and dendrimers based on reversible furan-maleimide
      Diels-Alder adducts.
AB  - [reaction: see text]. Benzyl aryl ether dendrons and dendrimers containing
      thermally reversible furan-maleimide Diels-Alder adducts were prepared up to the
      third generation. The covalent cleavage and reassembly of the dendrons and
      dendrimers were evaluated by 1H NMR.

PMID- 11506610
TI  - Unexpected reactivity of acetylenic omega-ketoesters toward TBAF and t-BuOK; new
      cascade reactions affording allene and oxetane derivatives.
AB  - [reaction: see text]. The reactivity of acetylenic omega-ketoesters toward tetra
      n-butylammonium fluoride and potassium tert-butoxide was studied. These cascade
      reactions proceeded smoothly and afforded either electrophilic allene derivatives
      or highly functionalized oxetane derivatives in moderate to high yields.

PMID- 11506609
TI  - Anodic coupling reactions: probing the stereochemistry of tetrahydrofuran
      formation. A short, convenient synthesis of linalool oxide.
AB  - [reaction: see text]. Intramolecular coupling reactions between enol ether
      radical cations and oxygen nucleophiles are primarily governed by
      stereoelectronics. By taking advantage of this observation, a tetrahydrofuran
      building block for use in constructing (+)-linalool oxide and rotundisine has
      been synthesized in four steps from a commercially available starting material.
      The synthesis of (+)-linalool oxide has been completed.

PMID- 11506611
TI  - Synthesis and biological activity of novel epothilone aziridines.
AB  - [reaction: see text]. A series of 12alpha,13alpha-aziridinyl epothilone
      derivatives were synthesized in an efficient manner from epothilone A. The final
      semisynthetic route involves a formal double-inversion of stereochemistry at both
      the C12 and C13 positions. All aziridine analogues were tested for effects on
      tubulin binding polymerization and cytotoxicity. The results indicate that the
      aziridine moiety is a viable isosteric replacement for the epoxide in the case of
      epothilones.

PMID- 11506612
TI  - Copper-catalyzed coupling reaction of terminal alkynes with aryl- and
      alkenyliodonium salts.
AB  - [reaction: see text]. The copper iodide-catalyzed cross-coupling of terminal
      alkynes with hypervalent iodonium salts was accomplished with CuI (10 mol %) and
      NaHCO3 (2 equiv) in DME/H2O (4:1) at room temperature for 30 min to afford
      arylalkynes or enynes under mild conditions.

PMID- 11506613
TI  - Studies toward the total synthesis of popolohuanone E: enantioselective synthesis
      of 8-O-methylpopolohuanone E.
AB  - [structure: see text]. 8-O-methylpopolohuanone E (2) was synthesized in a highly
      convergent manner starting from the cis-fused decalin derivative accessible from
      the (-)-Wieland-Miescher ketone analogue. The synthetic method features a
      biogenetic-type annulation of the phenolic and quinone segments to
      regioselectively construct the central tricyclic ring system as the key step.

PMID- 11506614
TI  - B(C6F5)3-catalyzed allylation of secondary benzyl acetates with allylsilanes.
AB  - [reaction: see text]. A highly effective protocol for allylation of secondary
      benzylic alcohol derivatives with allylsilanes in the presence of catalytic
      amounts of B(C6F5)3 has been developed. Some additional functionalities, such as
      bromo, acetoxy, and primary benzyloxy groups, were tolerated under these
      conditions.

PMID- 11506615
TI  - Radical [3+2] annulation of N-allyl-N-chlorotosylamide with alkenes via atom
      transfer process.
AB  - [reaction: see text]. A radical [3+2] annulation reaction with an N-centered
      radical has been developed. The reaction of alkenes with N-allyl-N
      chlorotosylamide yields the corresponding pyrrolidine derivatives in good yields
      in the presence of Et3B as a radical initiator.

PMID- 11506616
TI  - Concentration-dependent reactions of deoxofluor with arylglyoxal hydrates: a new
      route to polyfluoro ethers.
AB  - [reaction: see text]. In concentrated solutions (CH2Cl2) at 25 degrees C,
      arylglyoxal hydrates, ArCOCHO*H2O (Ar = 4-MeO-C6H4-, 4-Me-C6H4-, 4-F-C6H4-, Ph-,
      (2a-f) with Deoxofluor gave fluorinated ethers, ArCF2CHFOCHFCF2Ar, (3a-f) in >90%
      yields as meso/racemic mixtures (approximately 1:1). Under very dilute
      conditions, mixtures of ArCF2CHO (major) (4a-f) and ArCF2CF2H (6a-f) (minor) were
      obtained. The structures of 3b (racemic) and 4a (meso) have been confirmed by
      single-crystal X-ray analysis.

PMID- 11506617
TI  - Silicon-assisted ring opening of donor-acceptor substituted cyclopropanes. An
      expedient entry to substituted dihydrofurans.
AB  - [reaction: see text]. (tert-butyldiphenylsilyl)methylcyclopropanes undergo ring
      opening to furnish substituted dihydrofurans in good to excellent yields on
      treatment with TiCl4 in dichoromethane. The silicon that assists the
      regioselective ring opening is retained in the product to allow further
      functional group manipulations.

PMID- 11506618
TI  - Total synthesis of (-)-stemospironine.
AB  - [structure: see text]. A stereocontrolled total synthesis of the polycyclic
      Stemona alkaloid, (-)-stemospironine (1) has been achieved. Key transformations
      include the use of a Staudinger reaction leading to the aza-Wittig ring closure
      of the perhydroazepine system. Formation of the vicinal pyrrolidine butyrolactone
      is described via the stereoselective intramolecular capture of an intermediate
      aziridinium salt.

PMID- 11506619
TI  - Aspartic protease inhibitors: expedient synthesis of 2-substituted statines.
AB  - [reaction: see text]. General stereocontrolled synthesis of all four (2,3)
      stereoisomers of 2-substituted statines is described. The 2,3-syn and 2,3-anti
      isomers were synthesized via beta-ketoester reduction and aldol reactions,
      respectively. Peptides containing 2-substituted statines inhibit porcine pepsin
      with nanomolar IC50 values.

PMID- 11506620
TI  - Palladium-catalyzed synthesis of arylamines from aryl halides and lithium
      bis(trimethylsilyl)amide as an ammonia equivalent.
AB  - [reaction: see text]. A simple, palladium-catalyzed method to convert aryl
      halides to the parent anilines using lithium bis(trimethylsilyl)amide
      (LiN(SiMe3)2) is reported. The reaction is catalyzed by Pd(dba)2 and P(t-Bu)3 and
      can be run with as little as 0.2 mol % of catalyst. The reaction is faster than
      competing generation of benzyne intermediates and, therefore, provides the
      aniline products regiospecifically.

PMID- 11506621
TI  - The application of chiral aminonaphthols in the enantioselective addition of
      diethylzinc to aryl aldehydes.
AB  - [reaction: see text]. Optically active aminonaphthol 3 obtained by condensation
      of 2-naphthol, benzaldehyde, and (S)-methylbenzylamine followed by N-methylation
      was found to catalyze the enantioselective ethylation of aryl aldehydes to
      secondary alcohols with high enantioselectivities (up to 99.8%) at room
      temperature.

PMID- 11506622
TI  - A new, ring closing metathesis-based synthesis of (-)-fumagillol.
AB  - [reaction: see text]. A new strategy to access the fumagillin/fumagillol skeleton
      is proposed. An Evans aldolization and a RCM involving an enone are used for the
      preparation of a key cyclohexanone intermediate, which was readily converted to
      fumagillol. The synthesis also features an efficient preparation of isogeraniol
      and isogeranic acid.

PMID- 11506623
TI  - Synthesis of 2-alkyl- and 2-carboxy-p-tert-butylcalix[4]arenes via the lithiation
      of tetramethoxy-p-tert-butylcalix[4]arene.
AB  - [reaction: see text]. Tetramethoxy-p-tert-butylcalix[4]arene reacts readily with
      n-butyllithium to give a putative monolithiated intermediate that is substituted
      with alkyl halides and carbon dioxide to give in 60-75% yield conformationally
      mobile calix[4]arenes monosubstituted at the methylene bridge (2-position). 2
      Alkyl- and 2-benzyl-substituted tetramethoxycalix[4]arenes are converted in 62
      68% overall yield to the corresponding tetrahydroxy-p-tert-butylcalix[4]arenes by
      treatment with boron tribromide. The tetrahydroxy-p-tert-butylcalix[4]arenes
      exist in the cone conformation at room temperature in CDCl3 as judged by NMR
      spectroscopy.

PMID- 11506624
TI  - Titanium-mediated alkylative cyclizations of 1,3-diene-tethered esters.
AB  - [reaction: see text]. An alkylative titanium-mediated cyclization reaction of 1,3
      diene-tethered carboxylic esters has been developed by employing an in situ
      generated titanacyclopropane intermediate to afford trans-2-alkenyl
      cyclohexanols.

PMID- 11506625
TI  - Stereoselective syntheses of the C'D'E'F'-ring system of maitotoxin and the FG
      ring system of gambierol.
AB  - [structure: see text]. The stereoselective syntheses of the C'D'E'F'-ring system
      of maitotoxin and the FG-ring system of gambierol were accomplished. The key
      steps involve 6-endo-cyclization of methylepoxide, SmI2-induced reductive
      cyclization, 6-endo-cyclization of vinylepoxide, and formation of the lactone
      ring.

PMID- 11506626
TI  - Stereoselective synthesis of (Z)-enethiols and their derivatives: vinylic S(N)2
      reaction of (E)-alkenyl(phenyl)-lambda3-iodanes with thioamides.
AB  - [reaction: see text]. Exposure of (E)-beta-alkylvinyl(phenyl)-lambda3-iodanes to
      thioamides in dichloromethane at room temperature was found to result in a
      bimolecular nucleophilic substitution (S(N)2) at the vinylic carbon atom to give
      inverted (Z)-enethiols and/or (Z)-S-vinylthioimidonium salts. Vinylic S(N)2
      reactions with thioureas are also discussed.

PMID- 11506627
TI  - Sterically demanding, water-soluble alkylphosphines as ligands for high activity
      Suzuki coupling of aryl bromides in aqueous solvents.
AB  - [reaction: see text]. Sterically demanding, water-soluble alkylphosphines have
      been found to give highly active catalysts for Suzuki coupling of aryl bromides
      in aqueous solvents. A variety of aryl bromides and boronic acids were coupled in
      excellent yield. Turnover numbers up to 734 000 mmol/mmol Pd have been achieved
      under mild conditions.

PMID- 11506628
TI  - Photoinduced DNA cleavage by cyclopentadienyl metal complexes conjugated to DNA
      recognition elements.
AB  - [structure: see text]. DNA recognition elements have been attached to CpW(CO)3CH3
      and CpW(CO)3Ph, which produce methyl and phenyl radicals that cleave DNA upon
      photolysis. The inclusion of binding moieties in 3 increases the efficiency but
      not the selectivity of strand scission over that seen in the simple
      unfunctionalized complex, while 11 cleaves preferentially at T sites within AT
      rich tracts.

PMID- 11506629
TI  - An olefin cross-metathesis approach to vinylphosphonate-linked nucleic acids.
AB  - [reaction: see text]. The synthesis of vinylphosphonate-linked nucleotide dimers
      has been achieved using an olefin cross-metathesis (CM) reaction as a key step.
      The 1,3-dimesityl-4,5-dihydroimidazol-2-ylidine-containing catalyst 5 (Grubbs'
      second-generation catalyst) was found to be the superior catalyst for this
      transformation. Both metathesis partners were readily available using known
      methodology, and the vinylphosphonate-linked dimer was produced with high levels
      of (E)-selectivity (>20:1) in 58% yield (70% based on recovered starting
      material).

PMID- 11506630
TI  - A traceless perfluoroalkylsulfonyl (PFS) linker for the deoxygenation of phenols.
AB  - [reaction: see text]. The synthesis of a novel perfluoroalkylsulfonyl (PFS)
      fluoride is described for use as a traceless linker in solid-phase organic
      synthesis. Attachment to the resin and subsequent coupling of a phenol affords a
      stable arylsulfonate that behaves as a support-bound aryl triflate. Palladium
      mediated reductive cleavage of a wide variety of phenols generated the parent
      arenes. The resin-bound aryl triflate was shown to be stable to reductive
      amination conditions, and the traceless synthesis of Meclizine is reported.

PMID- 11506631
TI  - Tandem zirconocene homologation-aldimine allylation.
AB  - [reaction: see text]. Hydrozirconation of internal and terminal alkynes followed
      by in situ transmetalation to dimethylzinc and treatment with diiodomethane leads
      to chain extended allylic organometallics. Addition to N-phosphinoyl or N
      sulfonyl aldimines provides homoallylic amines in 48-87% yield and 3:2 to >20:1
      diastereomeric ratios favoring anti-products.

PMID- 11506632
TI  - An enantioselective synthesis of cryptocarya diacetate.
AB  - [reaction: see text]. The enantioselective synthesis of cryptocarya diacetate has
      been achieved in 10 steps from ethyl sorbate. The route relies upon an enantio-
      and regioselective Sharpless dihydroxylation and a palladium-catalyzed reduction
      to form a delta-hydroxy-1-enoate, which was subsequently converted into a
      benzylidene-protected 3,5-dihydroxy carboxylic ester. This ester was converted
      into cryptocarya diacetate in 14% overall yield via an allylation and methathesis
      ring closure reaction sequence.

PMID- 11506633
TI  - Reactions of amino alcohols in superacid: the direct observation of dicationic
      intermediates and their application in synthesis.
AB  - [reaction: see text]. The chemistry of amino alcohols has been studied in
      superacidic media, and these compounds have been found to ionize cleanly to the
      dication intermediates. Several dicationic species have been directly observed by
      low-temperature 13C NMR, including those from epinephrine (adrenaline) and
      synephrine. Amino alcohols react (70-99% yields) with C6H6 in triflic acid
      (CF3SO3H) by electrophilic aromatic substitution.

PMID- 11506634
TI  - Catalytic cyclopropanation of alkenes using diazo compounds generated in situ. A
      novel route to 2-arylcyclopropylamines.
AB  - [reaction: see text]. A user-friendly, one-pot process for catalytic
      cyclopropanation of alkenes from tosylhydrazones is described. The
      cyclopropanation of N-vinylphthalimide provides a new route to 2
      arylcyclopropylamines, and this is exemplified in the efficient synthesis of the
      HIV-1 reverse transcriptase inhibitor 6.

PMID- 11506635
TI  - Animal procedures remain vital to biomedical research: it ain't necessarily so...

PMID- 11506636
TI  - In vitro toxicology industrial platform (IVTIP) position paper, 9 February 2001:
      the role of an industrial platform in the area of in vitro testing.

PMID- 11506637
TI  - Novel advanced in vitro methods for long-term toxicity testing: the report and
      recommendations of ECVAM workshop 45. European Centre for the Validation of
      Alternative Methods.

PMID- 11506638
TI  - Guidelines for the design and statistical analysis of experiments in papers
      submitted to ATLA.
AB  - In vitro experiments need to be well designed and correctly analysed if they are
      to achieve their full potential to replace the use of animals in research. An
      "experiment" is a procedure for collecting scientific data in order to answer a
      hypothesis, or to provide material for generating new hypotheses, and differs
      from a survey because the scientist has control over the treatments that can be
      applied. Most experiments can be classified into one of a few formal designs, the
      most common being completely randomised, and randomised block designs. These are
      quite common with in vitro experiments, which are often replicated in time. Some
      experiments involve a single independent (treatment) variable, while other
      "factorial" designs simultaneously vary two or more independent variables, such
      as drug treatment and cell line. Factorial designs often provide additional
      information at little extra cost. Experiments need to be carefully planned to
      avoid bias, be powerful yet simple, provide for a valid statistical analysis and,
      in some cases, have a wide range of applicability. Virtually all experiments need
      some sort of statistical analysis in order to take account of biological
      variation among the experimental subjects. Parametric methods using the t test or
      analysis of variance are usually more powerful than non-parametric methods,
      provided the underlying assumptions of normality of the residuals and equal
      variances are approximately valid. The statistical analyses of data from a
      completely randomised design, and from a randomised-block design are demonstrated
      in Appendices 1 and 2, and methods of determining sample size are discussed in
      Appendix 3. Appendix 4 gives a checklist for authors submitting papers to ATLA.

PMID- 11506639
TI  - The use of bootstrap resampling to assess the uncertainty of cooper statistics.
AB  - The predictive abilities of two-group classification models (CMs) are often
      expressed in terms of their Cooper statistics. These statistics are often
      reported without any indication of their uncertainty, making it impossible to
      judge whether the predicted classifications are significantly better than the
      predictions made by a different CM, or whether the predictive performance of the
      CM exceeds predefined performance criteria in a statistically significant way.
      Bootstrap resampling routines are reported that provide a means of expressing the
      uncertainty associated with Cooper statistics. The usefulness of the
      bootstrapping routines is illustrated by constructing 95% confidence intervals
      for the Cooper statistics of four alternative skin-corrosivity tests (the rat
      skin transcutaneous electrical resistance assay, EPISKIN, Skin(2) and
      CORROSITEX), and four two-step sequences in which each in vitro test is used in
      combination with a physicochemical test for skin corrosion based on pH
      measurements.

PMID- 11506640
TI  - Lead inhibits growth and induces apoptosis in normal rat fibroblasts.
AB  - The effects on normal rat fibroblasts of lead supplementation (as lead acetate)
      in the medium were examined. The amount of lead acetate ranged from 0.078 microM
      to 320 microM, at 14 concentrations. The normal level of lead in the medium was
      0.060 microM, and the normal concentration of lead in the fibroblasts was 3.1 +/-
      0.1 ng/10(7) cells: these represented the control conditions. On studying
      fibroblast proliferation and survival after incubation for 48 hours, a lead
      acetate dose-dependent inhibition of cell proliferation was observed, the results
      being shown to be significant by ANOVA (p < 0.01), and suggesting a significant
      dose-response relationship. Apoptosis, evaluated by quantifying cytoplasmic DNA
      fragments, differs significantly between the lead levels tested. The distribution
      in the cell cycle, evaluated by using a fluorescence-activated cell sorter,
      showed a dose-dependent accumulation of cells in the G0/G1 phase, with a
      compensatory decrease in the percentage of cells in the S phase. Moreover, the
      occurrence of a subdiploid peak confirmed that apoptosis was more evident when
      the medium was supplemented with lead acetate at concentrations of 5-20 microM.
      The inhibition of cell growth is probably due to a direct inhibition of cell
      proliferation.

PMID- 11506641
TI  - The current status of food additives toxicity testing and the potential for
      application of the three Rs.

PMID- 11506643
TI  - Activity in human frontal cortex associated with spatial working memory and
      saccadic behavior.
AB  - We examined, with event-related fMRI, two hypotheses about the organization of
      human working memory function in frontal cortex: (1) that a region immediately
      anterior to the frontal eye fields (FEF) (superior frontal cortex, SFC) is
      specialized for spatial working memory (Courtney, et al., 1998); and (2) that
      dorsolateral prefrontal cortex (PFC) plays a privileged role in the manipulation
      of spatial stimuli held in working memory (Owen, et al., 1996; Petrides 1994).
      Our delayed-response task featured 2-D arrays of irregularly arranged squares
      that were highlighted serially in a random sequence. The Forward Memory condition
      required maintenance of the spatio-temporal sequence, the Manipulate Memory
      condition required reordering this sequence into a new spatially defined order,
      the Guided Saccade condition required saccades to highlighted squares in the
      array, but no memory, and the Free Saccade condition required self-paced,
      horizontal saccades. The comparison of fMRI signal intensity associated with 2-D
      saccade generation (Guided Saccades) versus fMRI signal intensity associated with
      the delay period of the working memorials condition revealed no evidence for
      greater working memory-related activity than saccade-related activity in SFC in
      any individual subject, nor at the level of the group, and greater 2-D saccade
      than delay-period activity in three of five subjects. These results fail to
      support the hypothesis that spatial working memory-related activity is
      represented preferentially in a region of SFC anterior to the FEF (Courtney, et
      al., 1998). The comparison of maintenance versus manipulation of spatio-temporal
      information in working memory revealed significantly greater activity associated
      with the latter in dorsolateral PFC, but not in ventrolateral PFC or in SFC.
      These results suggest that the delay-related function of SFC is limited to the
      maintenance of spatial information, and that this region does not support the
      nonmnemonic executive control functions supported by dorsolateral PFC. These
      results also indicate that the preferential recruitment of dorsolateral PFC for
      the manipulation of information held in working memory applies to tasks employing
      spatial stimuli, as well as to tasks employing verbal stimuli (D'Esposito, et
      al., 1999); Petrides et al., 1993; Postle et al., 1999).

PMID- 11506644
TI  - Transient activity in the human calcarine cortex during visual-mental imagery: an
      event-related fMRI study.
AB  - Although it is largely accepted that visual-mental imagery and perception draw on
      many of the same neural structures, the existence and nature of neural processing
      in the primary visual cortex (or area V1) during visual imagery remains
      controversial. We tested two general hypotheses: The first was that V1 is
      activated only when images with many details are formed and used, and the second
      was that V1 is activated whenever images are formed, even if they are not
      necessarily used to perform a task. We used event-related functional magnetic
      resonance imaging (ER-fMRI) to detect and characterize the activity in the
      calcarine sulcus (which contains the primary visual cortex) during single
      instances of mental imagery. The results revealed reproducible transient activity
      in this area whenever participants generated or evaluated a mental image. This
      transient activity was strongly enhanced when participants evaluated
      characteristics of objects, whether or not details actually needed to be
      extracted from the image to perform the task. These results show that visual
      imagery processing commonly involves the earliest stages of the visual system.

PMID- 11506645
TI  - Functional brain imaging of young, nondemented, and demented older adults.
AB  - Brain imaging based on functional MRI (fMRI) provides a powerful tool for
      characterizing age-related changes in functional anatomy. However, between
      population comparisons confront potential differences in measurement properties.
      The present experiment explores the feasibility of conducting fMRI studies in
      nondemented and demented older adults by measuring hemodynamic response
      properties in an event-related design. A paradigm involving repeated presentation
      of sensory-motor response trials was administered to 41 participants (14 young
      adults, 14 nondemented older adults, and 13 demented older adults). For half of
      the trials a single sensory-motor event was presented in isolation and in the
      other half in pairs. Hemodynamic response characteristics to the isolated events
      allowed basic response properties (e.g., amplitude and variance) between subject
      groups to be contrasted. The paired events further allowed the summation
      properties of the hemodynamic response to be characterized. Robust and
      qualitatively similar activation maps were produced for all subject groups.
      Quantitative results showed that for certain regions, such as in the visual
      cortex, there were marked reductions in the amplitude of the hemodynamic response
      in older adults. In other regions, such as in the motor cortex, relatively intact
      response characteristics were observed. These results suggest caution should be
      exhibited in interpreting simple main effects in response amplitude between
      subject groups. However, across all regions examined, the summation of the
      hemodynamic response over trials was highly similar between groups. This latter
      finding suggests that, even if absolute measurement differences do exist between
      subject groups, relative activation change should be preserved. Designs that rely
      on group interactions between task conditions, parametric manipulations, or group
      interactions between regions should provide valuable data for making inferences
      about functional-anatomic changes between different populations.

PMID- 11506646
TI  - The representation of objects in the human occipital and temporal cortex.
AB  - Recently, we identified, using fMRI, three bilateral regions in the ventral
      temporal cortex that responded preferentially to faces, houses, and chairs
      [Ishai, A., Ungerleider, L. G., Martin, A., Schouten, J. L., & Haxby, J. V.
      (1999). Distributed representation of objects in the human ventral visual
      pathway. Proceedings of the National Academy of Sciences, U.S.A., 96, 9379-
      9384]. Here, we report differential patterns of activation, similar to those seen
      in the ventral temporal cortex, in bilateral regions of the ventral occipital
      cortex. We also found category-related responses in the dorsal occipital cortex
      and in the superior temporal sulcus. Moreover, rather than activating discrete,
      segregated areas, each category was associated with its own differential pattern
      of response across a broad expanse of cortex. The distributed patterns of
      response were similar across tasks (passive viewing, delayed matching) and
      presentation formats (photographs, line drawings). We propose that the
      representation of objects in the ventral visual pathway, including both occipital
      and temporal regions, is not restricted to small, highly selective patches of
      cortex but, instead, is a distributed representation of information about object
      form. Within this distributed system, the representation of faces appears to be
      less extensive as compared to the representations of nonface objects.

PMID- 11506647
TI  - Interactions between forms of memory: when priming hinders new episodic learning.
AB  - Human memory consists of multiple forms, including priming and explicit memory.
      Although considerable evidence indicates that priming and explicit memory are
      functionally and neuroanatomically distinct, little is know about when and how
      these different forms of memory interact. Here, behavioral and functional
      magnetic resonance imaging (fMRI) methods were used to examine a novel and
      counterintuitive hypothesis: Priming during episodic encoding may be negatively
      associated with subsequent explicit memory. Using an experimental design that
      exploited known properties of spacing or lag effects, the magnitudes of
      behavioral and neural priming during a second study episode were varied and the
      relation between these magnitudes of priming during re-encoding and performance
      on a subsequent explicit memory test was examined. Results revealed that greater
      behavioral priming (reduced reaction times) and neural priming (reduced left
      inferior prefrontal brain activation) during re-encoding were associated with
      lower levels of subsequent explicit memory. Moreover, those subjects who
      demonstrated greater behavioral and neural priming effects during re-encoding
      following a long lag tended to demonstrate the least benefit in subsequent
      explicit memory due to this second study episode. These findings suggest that
      priming for past experiences can hinder new episodic encoding.

PMID- 11506648
TI  - Attention mechanisms in visual search -- an fMRI study.
AB  - The human visual system is usually confronted with many different objects at a
      time, with only some of them reaching consciousness. Reaction-time studies have
      revealed two different strategies by which objects are selected for further
      processing: an automatic, efficient search process, and a conscious, so-called
      inefficient search [Treisman, A. (1991). Search, similarity, and integration of
      features between and within dimensions. Journal of Experimental Psychology: Human
      Perception and Performance, 17, 652--676; Treisman, A., & Gelade, G. (1980). A
      feature integration theory of attention. Cognitive Psychology, 12, 97--136;
      Wolfe, J. M. (1996). Visual search. In H. Pashler (Ed.), Attention. London:
      University College London Press]. Two different theories have been proposed to
      account for these search processes. Parallel theories presume that both types of
      search are treated by a single mechanism that is modulated by attentional and
      computational demands. Serial theories, in contrast, propose that parallel
      processing may underlie efficient search, but inefficient searching requires an
      additional serial mechanism, an attentional "spotlight" (Treisman, A., 1991) that
      successively shifts attention to different locations in the visual field. Using
      functional magnetic resonance imaging (fMRI), we show that the cerebral networks
      involved in efficient and inefficient search overlap almost completely. Only the
      superior frontal region, known to be involved in working memory [Courtney, S. M.,
      Petit, L., Maisog, J. M., Ungerleider, L. G., & Haxby, J. V. (1998). An area
      specialized for spatial working memory in human frontal cortex. Science, 279,
      1347--1351], and distinct from the frontal eye fields, that control spatial
      shifts of attention, was specifically involved in inefficient search. Activity
      modulations correlated with subjects' behavior best in the extrastriate cortical
      areas, where the amount of activity depended on the number of distracting
      elements in the display. Such a correlation was not observed in the parietal and
      frontal regions, usually assumed as being involved in spatial attention
      processing. These results can be interpreted in two ways: the most likely is that
      visual search does not require serial processing, otherwise we must assume the
      existence of a serial searchlight that operates in the extrastriate cortex but
      differs from the visuospatial shifts of attention involving the parietal and
      frontal regions.

PMID- 11506649
TI  - Deconvolution of event-related fMRI responses in fast-rate experimental designs:
      tracking amplitude variations.
AB  - Recent developments towards event-related functional magnetic resonance imaging
      has greatly extended the range of experimental designs. If the events occur in
      rapid succession, the corresponding time-locked responses overlap significantly
      and need to be deconvolved in order to separate the contributions of different
      events. Here we present a deconvolution approach, which is especially aimed at
      the analysis of fMRI data where sequence- or context-related responses are
      expected. For this purpose, we make the assumption of a hemodynamic response
      function (HDR) with constant yet not predefined shape but with possibly variable
      amplitudes. This approach reduces the number of variables to be estimated but
      still keeps the solutions flexible with respect to the shape. Consequently,
      statistical efficiency is improved. Temporal variations of the HDR strength are
      directly indicated by the amplitudes derived by the algorithm. Both the
      estimation efficiency and statistical inference are further supported by an
      improved estimation of the noise covariance. Using synthesized data sets, both
      differently shaped HDRs and varying amplitude factors were correctly identified.
      The gain in statistical sensitivity led to improved ratios of false- and true
      positive detection rates for synthetic activations in these data. In an event
      related fMRI experiment with a human subject, different HDR amplitudes could be
      derived corresponding to stimulation at different visual stimulus contrasts.
      Finally, in a visual spatial attention experiment we obtained different fMRI
      response amplitudes depending on the sequences of attention conditions.

PMID- 11506650
TI  - The influence of memory load upon delay-interval activity in a working-memory
      task: an event-related functional MRI study.
AB  - We conducted two fMRI studies to investigate the sensitivity of delay-period
      activity to changes in memory load during a delayed-recognition task for faces.
      In Experiment 1, each trial began with the presentation of a memory array
      consisting of one, two, or three faces that lasted for 3 sec. A 15-sec delay
      period followed during which no stimuli were present. The delay interval
      concluded with a one-face probe to which subjects made a button press response
      indicating whether this face was part of the memory array. Experiment 2 was
      similar in design except that the delay period was lengthened to 24 sec, and the
      memory array consisted of only one or three faces. We hypothesized that memory
      maintenance processes that spanned the delay interval would be revealed by their
      sensitivity to memory load. Long delay intervals were employed to temporally
      dissociate phasic activity engendered by the memory array from sustained activity
      reflecting maintenance. Regions of interest (ROIs) were defined anatomically for
      the superior frontal gyri (SFG), middle frontal gyri (MFG), and inferior frontal
      gyri (IFG), intraparietal sulci (IPS), and fusiform gyri (FFG) on a subject-by
      subject basis. The mean time course of activity was determined for all voxels
      within these regions and for that subset of voxels within each ROI that
      correlated significantly with an empirically determined reference waveform. In
      both experiments, memory load significantly influenced activation 6--9 sec
      following the onset of the memory array with larger amplitude responses for
      higher load levels. Responses were greatest within MFG, IPS, and FFG. In both
      experiments, however, these load-sensitive differences declined over successive
      time intervals and were no longer significant at the end of the delay interval.
      Although insensitive to our load manipulation, sustained activation was present
      at the conclusion of the delay interval within MFG and other prefrontal regions.
      IPS delay activity returned to prestimulus baseline levels prior to the end of
      the delay period in Experiment 2, but not in Experiment 1. Within FFG, delay
      activity returned to prestimulus baseline levels prior to the conclusion of the
      delay interval in both experiments. Thus, while phasic processes engendered by
      the memory array were strongly affected by memory load, no evidence for load
      sensitive delay-spanning maintenance processes was obtained.

PMID- 11506651
TI  - Neural mechanisms of visual attention: object-based selection of a region in
      space.
AB  - Objects play an important role in guiding spatial attention through a cluttered
      visual environment. We used event-related functional magnetic resonance imaging
      (ER-fMRI) to measure brain activity during cued discrimination tasks requiring
      subjects to orient attention either to a region bounded by an object (object
      based spatial attention) or to an unbounded region of space (location-based
      spatial attention) in anticipation of an upcoming target. Comparison between the
      two tasks revealed greater activation when attention selected a region bounded by
      an object. This activation was strongly lateralized to the left hemisphere and
      formed a widely distributed network including (a) attentional structures in
      parietal and temporal cortex and thalamus, (b) ventral-stream object processing
      structures in occipital, inferior-temporal, and parahippocampal cortex, and (c)
      control structures in medial- and dorsolateral-prefrontal cortex. These results
      suggest that object-based spatial selection is achieved by imposing additional
      constraints over and above those processes already operating to achieve selection
      of an unbounded region. In addition, ER-fMRI methodology allowed a comparison of
      validly versus invalidly cued trials, thereby delineating brain structures
      involved in the reorientation of attention after its initial deployment proved
      incorrect. All areas of activation that differentiated between these two trial
      types resulted from greater activity during the invalid trials. This outcome
      suggests that all brain areas involved in attentional orienting and task
      performance in response to valid cues are also involved on invalid trials. During
      invalid trials, additional brain regions are recruited when a perceiver recovers
      from invalid cueing and reorients attention to a target appearing at an uncued
      location. Activated brain areas specific to attentional reorientation were
      strongly right-lateralized and included posterior temporal and inferior parietal
      regions previously implicated in visual attention processes, as well as
      prefrontal regions that likely subserve control processes, particularly related
      to inhibition of inappropriate responding.

PMID- 11506652
TI  - Neural activation during response competition.
AB  - The flanker task, introduced by Eriksen and Eriksen [Eriksen, B. A., & Eriksen,
      C. W. (1974). Effects of noise letters upon the identification of a target letter
      in a nonsearch task. Perception & Psychophysics, 16, 143--149], provides a means
      to selectively manipulate the presence or absence of response competition while
      keeping other task demands constant. We measured brain activity using functional
      magnetic resonance imaging (fMRI) during performance of the flanker task. In
      accordance with previous behavioral studies, trials in which the flanking stimuli
      indicated a different response than the central stimulus were performed
      significantly more slowly than trials in which all the stimuli indicated the same
      response. This reaction time effect was accompanied by increases in activity in
      four regions: the right ventrolateral prefrontal cortex, the supplementary motor
      area, the left superior parietal lobe, and the left anterior parietal cortex. The
      increases were not due to changes in stimulus complexity or the need to overcome
      previously learned associations between stimuli and responses. Correspondences
      between this study and other experiments manipulating response interference
      suggest that the frontal foci may be related to response inhibition processes
      whereas the posterior foci may be related to the activation of representations of
      the inappropriate responses.

PMID- 11506653
TI  - Order information in working memory: fMRI evidence for parietal and prefrontal
      mechanisms.
AB  - Working memory is thought to include a mechanism that allows for the coding of
      order information. One question of interest is how order information is coded,
      and how that code is neurally implemented. Here we report both behavioral and
      fMRI findings from an experiment involved comparing two tasks, an item-memory
      task and an order-memory task. In each case, five letters were presented for
      storage, followed after a brief interval by a set of probe letters. In the case
      of the item-memory task, the two letters were identical, and the subject
      responded to the question, "Was this letter one of the items you saw?". In the
      case of the order-memory task, the letters were different, and subjects responded
      to the question, "Are these two letters in the order in which you saw them?".
      Behaviorally, items that were further apart in the sequence that elicited faster
      reaction times and higher accuracy in the Order task. Areas that were
      significantly more activated in the Order condition included the parietal and
      prefrontal cortex. Parietal activations overlapped those involved in number
      processing, leading to the suggestion that the underlying representation of order
      and numbers may share a common process, coding for magnitude.

PMID- 11506654
TI  - The effects of presentation rate during word and pseudoword reading: a comparison
      of PET and fMRI.
AB  - The effect of stimulus rate and its interaction with stimulus type on brain
      activity during reading was investigated using functional magnetic resonance
      imaging (fMRI). This (i) enabled the segregation of brain regions showing
      differential responses, (ii) identified the optimum experimental design
      parameters for maximizing sensitivity, and (iii) allowed us to evaluate further
      the sources of discrepancy between positron emission tomography (PET) and fMRI
      signals. The effect of visual word rate has already been investigated in a
      previous PET study. However, rate effects can be very different in PET and fMRI,
      as seen in previous studies of auditory word processing. In this work, we attempt
      to replicate rate-sensitive activations observed with PET using fMRI. Our
      objective was to characterize the discrepancies in regionally specific rate
      sensitive effects between the two imaging modalities. Subjects were presented
      with words and pseudowords at varying rates while performing a silent reading
      task. The analysis specifically identified regions showing (i) an effect of
      stimulus rate on brain activity during reading; (ii) modulation of this effect by
      word type; and (iii) increased activity during reading relative to rest, but with
      no dependence on stimulus rate. The results identified similar effects of rate
      for words and pseudowords (no interactions between rate and word type reached
      significance). Irrespective of word type, strong positive linear effects of rate
      (i.e., activity increasing with rate) were detected in visual areas, right
      superior temporal gyrus, and bilateral precentral gyrus. These findings replicate
      the results of the previous PET study, confirming that activation in regions
      associated with visual processing and response generation increases with the
      number of stimuli. Likewise, we detected rate-independent effects reported in the
      previous PET study in bilateral anterior middle temporal, inferior frontal, and
      superior parietal regions. These results differentiate the functionally specific
      responses in rate-dependent and rate-independent areas. However, for negative
      effects of rate, fMRI did not replicate the effects seen in PET, suggesting some
      form of hemodynamic "rectification." The discussion focuses on differences
      between evoked rCBF and BOLD signals.

PMID- 11506655
TI  - The emotional modulation of cognitive processing: an fMRI study.
AB  - The functional neuroanatomy of visual processing of surface features of
      emotionally valenced pictorial stimuli was examined in normal human subjects
      using functional magnetic resonance imaging (fMRI). Pictorial stimuli were of two
      types: emotionally negative and neutral pictures. Task performance was slower for
      the negatively valenced than for the neutral pictures. Significant blood oxygen
      level dependent (BOLD) increases occurred in the medial and dorsolateral
      prefrontal cortex, midbrain, substantia innominata, and/or amygdala, and in the
      posterior cortical visual areas for both stimulus types. Increases were greater
      for the negatively valenced stimuli. While there was a small but significant BOLD
      decrease in the subgenual prefrontal cortex, which was larger in response to the
      negatively valenced pictures, there was an almost complete absence of other
      decreases prominently seen during the performance of demanding cognitive tasks
      [Shulman, G. L., Fiez, J. A., Corbetta, M., Buckner, R. L., Miezin, F. M.,
      Raichle, M. E., & Petersen, S. E. (1997). Common blood flow changes across visual
      tasks: II. Decreases in cerebral cortex. Journal of Cognitive Neuroscience, 9,
      648--663]. These results provide evidence that the emotional valence and arousing
      nature of stimuli used during the performance of an attention-demanding cognitive
      task are reflected in discernable, quantitative changes in the functional anatomy
      associated with task performance.

PMID- 11506656
TI  - An empirical explanation of the Chubb illusion.
AB  - The perceived difference in brightness between elements of a patterned target is
      diminished when the target is embedded in a similar surround of higher luminance
      contrast (the Chubb illusion). Here we show that this puzzling effect can be
      explained by the degree to which imperfect transmittance is likely to have
      affected the light that reaches the eye. These observations indicate that this
      'illusion' is yet another signature of the fundamentally empirical strategy of
      visual perception, in this case generated by the typical influence of
      transmittance on inherently ambiguous stimuli.

PMID- 11506657
TI  - Prosopagnosia as a deficit in encoding curved surface.
AB  - RP is a case of "developmental" prosopagnosia who, according to brain-imaging
      segmentation data, shows reduction in volume of a limited set of structures of
      the right hemisphere. RP is as accurate as control subjects in tasks requiring
      the perception of nonface objects (e.g., matching subordinate labels to
      exemplars, naming two-tone images), with the exception of one perceptual task:
      The matching of different perspectives of amoebae-like stimuli (i.e., volumes
      made of a single smooth surface). In terms of speed ("efficiency") of responses,
      RP's performance falls clearly outside the normal limits also in other tasks that
      include "natural" but nonface stimuli (i.e., animals, artia facts). Specifically,
      RP is slow in perceptual judgments made at very low (subordinate) levels of
      semantic categorization and for objects and artifacts whose geometry present much
      curved features and surface information. We conclude from these analyses that
      prosopagnosia can be the result of a deficit in the representation of basic
      geometric volumes made of curved surface. In turn, this points to the importance
      (necessity) for the normal visual system of such curved and volumetric
      information in the identification of human faces.

PMID- 11506658
TI  - Electrophysiological correlates of emotion-induced recognition bias.
AB  - The question of how emotions influence recognition memory is of interest not only
      within basic cognitive neuroscience but from clinical and forensic perspectives
      as well. Emotional stimuli can induce a "recognition bias" such that individuals
      are more likely to respond "old" to a negative item than to an emotionally
      neutral item, whether the item is actually old or new. We investigated this bias
      using event-related brain potential (ERP) measures by comparing the processing of
      words given "old" responses with accurate recognition of old/new differences. For
      correctly recognized items, the ERP difference between old items (hits) and new
      items (correct rejections, CR) was largely unaffected by emotional valence. That
      is, regardless of emotional valence, the ERP associated with hits was
      characterized by a widespread positivity between 300 and 700 msec relative to
      that for CRs. By contrast, the analysis of ERPs to old and new items that were
      judged "old" (hits and false alarms [FAs], respectively) revealed a differential
      effect of valence by 300 msec: Neutral items showed a large old/new difference
      over prefrontal sites, whereas negative items did not. These results are the
      first clear demonstration of response bias effects on ERPs linked to recognition
      memory. They are consistent with the idea that frontal cortex areas may be
      responsible for relaxing the retrieval criterion for negative stimuli so as to
      ensure that emotional events are not as easily "missed" or forgotten as neutral
      events.

PMID- 11506659
TI  - Does the medial temporal lobe bind phonological memories?
AB  - The medial temporal lobes play a central role in the consolidation of new
      memories. Medial temporal lesions impair episodic learning in amnesia, and
      disrupt vocabulary acquisition. To investigate the role of consolidation
      processes in phonological memory and to understand where and how, in amnesia,
      these processes begin to fail, we reexamined phonological memory in the amnesic
      patient HM. While HM's word span performance was normal, his supraspan recall was
      shown to be markedly impaired, with his recall characterized by a distinctive
      pattern of phonological errors, where he recombined phonemes from the original
      list to form new response words. These were similar to errors observed earlier
      for patients with specifically semantic deficits. Amnesic Korsakoff's patients
      showed a similar, though much less marked, pattern. We interpret the data in
      terms of a model of lexical representation where temporal lobe damage disrupts
      the processes that normally bind semantic and phonological representations.

PMID- 11506660
TI  - Phonological processing in visual rhyming: a developmental erp study.
AB  - We employed a visual rhyming priming paradigm to characterize the development of
      brain systems important for phonological processing in reading. We studied 109
      righthanded, native English speakers within eight age groups: 7-8, 9-10, 11-12,
      13-14, 15-16, 17-18, 19-20, and 21-23. Participants decided whether two written
      words (prime-target) rhymed (JUICE-MOOSE) or not (CHAIR-MOOSE). In similar
      studies of adults, two main event-related potential (ERP) effects have been
      described: a negative slow wave to primes, larger over anterior regions of the
      left hemisphere and hypothesized to index rehearsal of the primes, and a negative
      deflection to targets, peaking at 400-450 msec, maximal over right temporal
      parietal regions, larger for nonrhyming than rhyming targets, and hypothesized
      index phonological matching. In this study, these two ERP effects were observed
      in all age groups; however, the two effects showed different developmental
      timecourses. On the one hand, the frontal asymmetry to primes increased with age;
      moreover, this asymmetry was correlated with reading and spelling scores, even
      after controlling for age. On the other hand, the distribution and onset of the
      more posterior rhyming effect (RE) were stable across age groups, suggesting that
      phonological matching relied on similar neural systems across these ages.
      Behaviorally, both reaction times and accuracy improved with age. These results
      suggest that different aspects of phonological processing rely on different
      neural systems that have different to developmental timecourses.

PMID- 11506661
TI  - Parallel cortico-basal ganglia mechanisms for acquisition and execution of
      visuomotor sequences - a computational approach.
AB  - Experimental studies have suggested that many brain areas, including the basal
      ganglia (BG), contribute to procedural learning. Focusing on the basal ganglia
      thalamocortical (BG-TC) system, we propose a computational model to explain how
      different brain areas work together in procedural learning. The BG-TC system is
      composed of multiple separate loop circuits. According to our model, two separate
      BG-TC loops learn a visuomotor sequence concurrently but using different
      coordinates, one visual, and the other motor. The visual loop includes the
      dorsolateral prefrontal (DLPF) cortex and the anterior part of the BG, while the
      motor loop includes the supplementary motor area (SMA) and the posterior BG. The
      concurrent learning in these loops is based on reinforcement signals carried by
      dopaminergic (DA) neurons that project divergently to the anterior ("visual") and
      posterior ("motor") parts of the striatum. It is expected, however, that the
      visual loop learns a sequence faster than the motor loop due to their different
      coordinates. The difference in learning speed may lead to inconsistent outputs
      from the visual and motor loops, and this problem is solved by a mechanism called
      a "coordinator," which adjusts the contribution of the visual and motor loops to
      a final motor output. The coordinator is assumed to be in the presupplementary
      motor area (pre-SMA). We hypothesize that the visual and motor loops, with the
      help of the coordinator, achieve both the quick acquisition of novel sequences
      and the robust execution of well-learned sequences. A computational model based
      on the hypothesis is examined in a series of computer simulations, referring to
      the results of the 2 x 5 task experiments that have been used on both monkeys and
      humans. We found that the dual mechanism with the coordinator was superior to the
      single (visual or motor) mechanism. The model replicated the following essential
      features of the experimental results: (1) the time course of learning, (2) the
      effect of opposite hand use, (3) the effect of sequence reversal, and (4) the
      effects of localized brain inactivations. Our model may account for a common
      feature of procedural learning: A spatial sequence of discrete actions (subserved
      by the visual loop) is gradually replaced by a robust motor skill (subserved by
      the motor loop).

PMID- 11506662
TI  - Amnesia and the declarative/nondeclarative distinction: a recurrent network model
      of classification, recognition, and repetition priming.
AB  - A key claim of current theoretical analyses of the memory impairments associated
      with amnesia is that certain distinct forms of learning and memory are spared.
      Supporting this claim, B. J. Knowlton and L. R. Squire found that amnesic
      patients and controls were indistinguishable in their ability to learn about and
      classify strings of letters generated from a finite-state grammar, but that the
      amnesics were impaired at recognizing the training strings. We show, first, that
      this pattern of results is predicted by a single-system connectionist model of
      artificial grammar learning (AGL) in which amnesia is simulated by a reduced
      learning rate. We then show in two experiments that a counterintuitive assumption
      of this model, that classification and recognition are functionally identical in
      AGL, is correct. In three further simulation studies, we demonstrate that the
      model also reproduces another type of dissociation, namely between recognition
      memory and repetition priming. We conclude that the performance of amnesic
      patients in memory tasks is better understood in terms of a nonselective, rather
      than a selective, memory deficit.

PMID- 11506663
TI  - Visual priming within and across symbolic format using a tachistoscopic picture
      identification task: a PET study.
AB  - The present work was aimed at characterizing picture priming effects from two
      complementary behavioral and functional neuroimaging (positron emission
      tomography, PET) studies. In two experiments, we used the same line drawings of
      common living/nonliving objects in a tachistoscopic identification task to
      contrast two forms of priming. In the within-format priming condition (picture
      picture), subjects were instructed to perform a perceptual encoding task in the
      study phase, whereas in the cross-format priming condition (word-picture), they
      were instructed to perform a semantic encoding task. In Experiment 1, we showed
      significant priming effects in both priming conditions. However, the magnitude of
      priming effects in the same-format/perceptual encoding condition was higher than
      that in the different-format/semantic encoding condition, while the recognition
      performance did not differ between the two conditions. This finding supports the
      existence of two forms of priming that may be subserved by different systems.
      Consistent with these behavioral findings, the PET data for Experiment 2 revealed
      distinct priming-related patterns of regional cerebral blood flow (rCBF)
      decreases for the two priming conditions when primed items were compared to
      unprimed items. The same-format priming condition involved reductions in cerebral
      activity particularly in the right extrastriate cortex and left cerebellum, while
      the different-format priming condition was associated with rCBF decreases in the
      left inferior temporo-occipital cortex, left frontal regions, and the right
      cerebellum. These results suggest that the extrastriate cortex may subserve
      general aspects of perceptual priming, independent of the kind of stimuli, and
      that the right part of this cortex could underlie the same-format-specific system
      for pictures. These data also support the idea that the cross-format/semantic
      encoding priming for pictures represents a form of lexico-semantic priming
      subserved by a semantic neural network extending from left temporo-occipital
      cortex to left frontal regions. These results reinforce the distinction between
      perceptual and conceptual priming for pictures, indicating that different
      cerebral processes and systems are implicated in these two forms of picture
      priming.

PMID- 11506664
TI  - Relations between the neural bases of dynamic auditory processing and
      phonological processing: evidence from fMRI.
AB  - Functional magnetic resonance imaging (fMRI) was used to examine how the brain
      responds to temporal compression of speech and to determine whether the same
      regions are also involved in phonological processes associated with reading.
      Recorded speech was temporally compressed to varying degrees and presented in a
      sentence verification task. Regions involved in phonological processing were
      identified in a separate scan using a rhyming judgment task with pseudowords
      compared to a lettercase judgment task. The left inferior frontal and left
      superior temporal regions (Broca's and Wernicke's areas), along with the right
      inferior frontal cortex, demonstrated a convex response to speech compression;
      their activity increased as compression increased, but then decreased when speech
      became incomprehensible. Other regions exhibited linear increases in activity as
      compression increased, including the middle frontal gyri bilaterally. The
      auditory cortices exhibited compression-related decreases bilaterally, primarily
      reflecting a decrease in activity when speech became incomprehensible. Rhyme
      judgments engaged two left inferior frontal gyrus regions (pars triangularis and
      pars opercularis), of which only the pars triangularis region exhibited
      significant compression-related activity. These results directly demonstrate that
      a subset of the left inferior frontal regions involved in phonological processing
      is also sensitive to transient acoustic features within the range of
      comprehensible speech.

PMID- 11506665
TI  - The attentional role of the left parietal cortex: the distinct lateralization and
      localization of motor attention in the human brain.
AB  - It is widely agreed that visuospatial orienting attention depends on a network of
      frontal and parietal areas in the right hemisphere. It is thought that the
      visuospatial orienting role of the right parietal lobe is related to its role in
      the production of overt eye movements. The experiments reported here test the
      possibility that other parietal regions may be important for directing attention
      in relation to response modalities other than eye movement. Specifically, we used
      positron emission tomography (PET) to test the hypothesis that a 'left' parietal
      area, the supramarginal gyrus, is important for attention in relation to limb
      movements (Rushworth et al., 1997; Rushworth, Ellison, & Walsh, in press). We
      have referred to this process as 'motor attention' to distinguish it from
      orienting attention. In one condition subjects spent most of the scanning period
      covertly attending to 'left' hand movements that they were about to make.
      Activity in this first condition was compared with a second condition with
      identical stimuli and movement responses but lacking motor attention periods.
      Comparison of the conditions revealed that motor attention-related activity was
      almost exclusively restricted to the 'left' hemisphere despite the fact that
      subjects only ever made ipsilateral, left-hand responses. Left parietal activity
      was prominent in this comparison, within the parietal lobe the critical region
      for motor attention was the supramarginal gyrus and the adjacent anterior
      intraparietal sulcus (AIP), a region anterior to the posterior parietal cortex
      identified with orienting attention. In a second part of the experiment we
      compared a condition in which subjects covertly rehearsed verbal responses with a
      condition in which they made verbal responses immediately without rehearsal. A
      comparison of the two conditions revealed verbal rehearsal-related activity in
      several anterior left hemisphere areas including Broca's area. The lack of verbal
      rehearsal-related activity in the left supra-marginal gyrus confirms that this
      area plays a direct role in motor attention that cannot be attributed to any
      strategy of verbal mediation. The results also provide evidence concerning the
      importance of ventral premotor (PMv) and Broca's area in motor attention and
      language processes.

PMID- 11506666
TI  - Orientation, scale, and discontinuity as emergent properties of illusory contour
      shape.
AB  - A recent neural model of illusory contour formation is based on a distribution of
      natural shapes traced by particles moving with constant speed in directions given
      by Brownian motions. The input to that model consists of pairs of position and
      direction constraints, and the output consists of the distribution of contours
      joining all such pairs. In general, these contours will not be closed, and their
      distribution will not be scale-invariant. In this article, we show how to compute
      a scale-invariant distribution of closed contours given position constraints
      alone and use this result to explain a well-known illusory contour effect.

PMID- 11506667
TI  - A spike-train probability model.
AB  - Poisson processes usually provide adequate descriptions of the irregularity in
      neuron spike times after pooling the data across large numbers of trials, as is
      done in constructing the peristimulus time histogram. When probabilities are
      needed to describe the behavior of neurons within individual trials, however,
      Poisson process models are often inadequate. In principle, an explicit formula
      gives the probability density of a single spike train in great generality, but
      without additional assumptions, the firing-rate intensity function appearing in
      that formula cannot be estimated. We propose a simple solution to this problem,
      which is to assume that the time at which a neuron fires is determined
      probabilistically by, and only by, two quantities: the experimental clock time
      and the elapsed time since the previous spike. We show that this model can be
      fitted with standard methods and software and that it may used successfully to
      fit neuronal data.

PMID- 11506668
TI  - Orientation tuning properties of simple cells in area V1 derived from an
      approximate analysis of nonlinear neural field models.
AB  - We present a general approximation method for the mathematical analysis of
      spatially localized steady-state solutions in nonlinear neural field models.
      These models comprise several layers of excitatory and inhibitory cells. Coupling
      kernels between and inside layers are assumed to be gaussian shaped. In response
      to spatially localized (i.e., tuned) inputs, such networks typically reveal
      stationary localized activity profiles in the different layers. Qualitative
      properties of these solutions, like response amplitudes and tuning widths, are
      approximated for a whole class of nonlinear rate functions that obey a power law
      above some threshold and that are zero below. A special case of these functions
      is the semilinear function, which is commonly used in neural field models. The
      method is then applied to models for orientation tuning in cortical simple cells:
      first, to the one-layer model with "difference of gaussians" connectivity kernel
      developed by Carandini and Ringach (1997) as an abstraction of the biologically
      detailed simulations of Somers, Nelson, and Sur (1995); second, to a two-field
      model comprising excitatory and inhibitory cells in two separate layers. Under
      certain conditions, both models have the same steady states. Comparing
      simulations of the field models and results derived from the approximation
      method, we find that the approximation well predicts the tuning behavior of the
      full model. Moreover, explicit formulas for approximate amplitudes and tuning
      widths in response to changing input strength are given and checked numerically.
      Comparing the network behavior for different nonlinearities, we find that the
      only rate function (from the class of functions under study) that leads to
      constant tuning widths and a linear increase of firing rates in response to
      increasing input is the semilinear function. For other nonlinearities, the
      qualitative network response depends on whether the model neurons operate in a
      convex (e.g., x(2)) or concave (e.g., sqrt(x)) regime of their rate function. In
      the first case, tuning gradually changes from input driven at low input strength
      (broad tuning strongly depending on the input and roughly linear amplitudes in
      response to input strength) to recurrently driven at moderate input strength
      (sharp tuning, supralinear increase of amplitudes in response to input strength).
      For concave rate functions, the network reveals stable hysteresis between a state
      at low firing rates and a tuned state at high rates. This means that the network
      can "memorize" tuning properties of a previously shown stimulus. Sigmoid rate
      functions can combine both effects. In contrast to the Carandini-Ringach model,
      the two-field model further reveals oscillations with typical frequencies in the
      beta and gamma range, when the excitatory and inhibitory connections are
      relatively strong. This suggests a rhythmic modulation of tuning properties
      during cortical oscillations.

PMID- 11506669
TI  - Computational design and nonlinear dynamics of a recurrent network model of the
      primary visual cortex.
AB  - Recurrent interactions in the primary visual cortex make its output a complex
      nonlinear transform of its input. This transform serves preattentive visual
      segmentation, that is, autonomously processing visual inputs to give outputs that
      selectively emphasize certain features for segmentation. An analytical
      understanding of the nonlinear dynamics of the recurrent neural circuit is
      essential to harness its computational power. We derive requirements on the
      neural architecture, components, and connection weights of a biologically
      plausible model of the cortex such that region segmentation, figure-ground
      segregation, and contour enhancement can be achieved simultaneously. In addition,
      we analyze the conditions governing neural oscillations, illusory contours, and
      the absence of visual hallucinations. Many of our analytical techniques can be
      applied to other recurrent networks with translation-invariant neural and
      connection structures.

PMID- 11506670
TI  - A hierarchical dynamical map as a basic frame for cortical mapping and its
      application to priming.
AB  - A hierarchical dynamical map is proposed as the basic framework for sensory
      cortical mapping. To show how the hierarchical dynamical map works in cognitive
      processes, we applied it to a typical cognitive task known as priming, in which
      cognitive performance is facilitated as a consequence of prior experience. Prior
      to the priming task, the network memorizes a sensory scene containing multiple
      objects presented simultaneously using a hierarchical dynamical map. Each object
      is composed of different sensory features. The hierarchical dynamical map
      presented here is formed by random itinerancy among limit-cycle attractors into
      which these objects are encoded. Each limit-cycle attractor contains multiple
      point attractors into which elemental features belonging to the same object are
      encoded. When a feature stimulus is presented as a priming cue, the network state
      is changed from the itinerant state to a limit-cycle attractor relevant to the
      priming cue. After a short priming period, the network state reverts to the
      itinerant state. Under application of the test cue, consisting of some feature
      belonging to the object relevant to the priming cue and fragments of features
      belonging to others, the network state is changed to a limit-cycle attractor and
      finally to a point attractor relevant to the target feature. This process is
      considered as the identification of the target. The model consistently reproduces
      various observed results for priming processes such as the difference in
      identification time between cross-modality and within-modality priming tasks, the
      effect of interval between priming cue and test cue on identification time, the
      effect of priming duration on the time, and the effect of repetition of the same
      priming task on neural activity.

PMID- 11506671
TI  - Dynamical stability conditions for recurrent neural networks with unsaturating
      piecewise linear transfer functions.
AB  - We establish two conditions that ensure the nondivergence of additive recurrent
      networks with unsaturating piecewise linear transfer functions, also called
      linear threshold or semilinear transfer functions. As Hahnloser, Sarpeshkar,
      Mahowald, Douglas, and Seung (2000) showed, networks of this type can be
      efficiently built in silicon and exhibit the coexistence of digital selection and
      analog amplification in a single circuit. To obtain this behavior, the network
      must be multistable and nondivergent, and our conditions allow determining the
      regimes where this can be achieved with maximal recurrent amplification. The
      first condition can be applied to nonsymmetric networks and has a simple
      interpretation of requiring that the strength of local inhibition match the sum
      over excitatory weights converging onto a neuron. The second condition is
      restricted to symmetric networks, but can also take into account the stabilizing
      effect of nonlocal inhibitory interactions. We demonstrate the application of the
      conditions on a simple example and the orientation-selectivity model of Ben
      Yishai, Lev Bar-Or, and Sompolinsky (1995). We show that the conditions can be
      used to identify in their model regions of maximal orientation-selective
      amplification and symmetry breaking.

PMID- 11506672
TI  - An information-based neural approach to constraint satisfaction.
AB  - A novel artificial neural network approach to constraint satisfaction problems is
      presented. Based on information-theoretical considerations, it differs from a
      conventional mean-field approach in the form of the resulting free energy. The
      method, implemented as an annealing algorithm, is numerically explored on a
      testbed of K-SAT problems. The performance shows a dramatic improvement over that
      of a conventional mean-field approach and is comparable to that of a state-of-the
      art dedicated heuristic (GSAT+walk). The real strength of the method, however,
      lies in its generality. With minor modifications, it is applicable to arbitrary
      types of discrete constraint satisfaction problems.

PMID- 11506673
TI  - Recurrence methods in the analysis of learning processes.
AB  - The goal of most learning processes is to bring a machine into a set of "correct"
      states. In practice, however, it may be difficult to show that the process enters
      this target set. We present a condition that ensures that the process visits the
      target set infinitely often almost surely. This condition is easy to verify and
      is true for many well-known learning rules. To demonstrate the utility of this
      method, we apply it to four types of learning processes: the perceptron, learning
      rules governed by continuous energy functions, the Kohonen rule, and the
      committee machine.

PMID- 11506674
TI  - Subspace information criterion for model selection.
AB  - The problem of model selection is considerably important for acquiring higher
      levels of generalization capability in supervised learning. In this article, we
      propose a new criterion for model selection, the subspace information criterion
      (SIC), which is a generalization of Mallows's C(L). It is assumed that the
      learning target function belongs to a specified functional Hilbert space and the
      generalization error is defined as the Hilbert space squared norm of the
      difference between the learning result function and target function. SIC gives an
      unbiased estimate of the generalization error so defined. SIC assumes the
      availability of an unbiased estimate of the target function and the noise
      covariance matrix, which are generally unknown. A practical calculation method of
      SIC for least-mean-squares learning is provided under the assumption that the
      dimension of the Hilbert space is less than the number of training examples.
      Finally, computer simulations in two examples show that SIC works well even when
      the number of training examples is small.

PMID- 11506675
TI  - Convergent decomposition techniques for training RBF neural networks.
AB  - In this article we define globally convergent decomposition algorithms for
      supervised training of generalized radial basis function neural networks. First,
      we consider training algorithms based on the two-block decomposition of the
      network parameters into the vector of weights and the vector of centers. Then we
      define a decomposition algorithm in which the selection of the center locations
      is split into sequential minimizations with respect to each center, and we give a
      suitable criterion for choosing the centers that must be updated at each step. We
      prove the global convergence of the proposed algorithms and report the
      computational results obtained for a set of test problems.

PMID- 11506677
TI  - Self-organized dynamics in spatially structured populations.
AB  - Self-organization and pattern formation represent the emergence of order in
      temporal and spatial processes. Self-organization in population ecology is
      gaining attention due to the recent advances concerning temporal fluctuations in
      the population size of dispersal-linked subunits. We shall report that spatially
      structured models of population renewal promote the emergence of a complex power
      law order in spatial population dynamics. We analyse a variety of population
      models showing that self-organization can be identified as a temporal match in
      population dynamics among local units, and how the synchrony changes in time. Our
      theoretical results are concordant with analyses of population data on the Canada
      lynx.

PMID- 11506676
TI  - The Acp26Aa seminal fluid protein is a modulator of early egg hatchability in
      Drosophila melanogaster.
AB  - Drosophila melanogaster male accessory gland proteins (Acps) that are transferred
      in the ejaculate with sperm mediate post-mating competition for fertilizations
      between males. The actions of Acps include effects on oviposition and ovulation,
      receptivity and sperm storage. Two Acps that modulate egg production are Acp26Aa
      (ovulin) and Acp70A (the sex peptide). Acp26Aa acts specifically on the process
      of ovulation (the release of mature eggs from the ovaries), which is initiated
      1.5 h after mating. In contrast, sperm storage can take as long as 6-9 h to
      complete. Initial ovulations after matings by virgin females will therefore occur
      before all sperm are fully stored and the extra eggs initially laid as a result
      of Acp26Aa transfer are expected to be inefficiently fertilized. Acp26Aa-mediated
      release of existing eggs should not cause a significant energetic cost or lead to
      a decrease in female lifespan assuming, as seems likely, that the energetic cost
      of egg laying comes from de novo egg synthesis (oogenesis) rather than from
      ovulation. We tested these predictions using Acp26Aa(1) mutant males that lack
      Acp26Aa but are normal for other Acps and Acp26Aa(2) males that transfer a
      truncated but fully functional Acp26Aa protein. Females mating with Acp26Aa(2)
      (truncation) males that received functional Acp26Aa produced significantly more
      eggs following their first matings than did mates of Acp26Aa(1) (null) males.
      However, as predicted above, these extra eggs, which were laid as a result of
      Acp26Aa transfer to virgin females, showed significantly lower egg hatchability.
      Control experiments indicated that this lower hatchability was due to lower rates
      of fertilization at early post-mating times. There was no drop in egg
      hatchability in subsequent non-virgin matings. In addition, as predicted above,
      females that did or did not receive Acp26Aa did not differ in survival, lifetime
      fecundity or lifetime progeny, indicating that Acp26Aa transfer does not
      represent a significant energetic cost for females and does not contribute to the
      survival cost of mating. Acp26Aa appears to remove a block to oogenesis by
      causing the clearing out of existing mature eggs and, thus, indirectly allowing
      oogenesis to be initiated immediately after mating. The results show that subtle
      processes coordinate the stimulation of egg production and sperm storage in
      mating pairs.

PMID- 11506678
TI  - Sexual conflict and cooperation in butterfly reproduction: a comparative study of
      polyandry and female fitness.
AB  - Most butterfly species can be characterized as capital breeders, meaning that
      reproductive output is strongly coupled to the amount of resources they have
      procured during the larval stage. Accordingly, female fecundity is generally
      correlated with female mass, both within and across species. However, the females
      of some species can be partly characterized as income breeders, in the sense that
      their reproductive output is dependent not only on larval-derived capital but
      also on resources acquired during the adult stage. These adult resources can be
      derived from female feeding or from male-transferred nuptial gifts. Recent
      studies on the within-species effects of multiple matings on female fitness show
      that females generally gain directly from multiple matings in terms of increased
      lifetime offspring production. Here, we test whether the positive effects of
      multiple mating on female fitness also hold at a comparative level, by conducting
      a laboratory study of female reproductive output in eight pierid species that
      differ in life-time female mating frequency. Female reproductive output, measured
      as cumulative egg mass divided by female mass, increased significantly with
      polyandry (r = 0.942, p < 0.001), demonstrating that the positive effect of
      mating rate on female reproductive fitness also holds between species. The
      positive effect of male nutrient contribution is substantial, and the per capita
      reproductive output is more than twice as high in the most polyandrous species as
      in the most monandrous ones. Hence, the positive net effect of the ejaculates is
      highly substantial, although males and females can have sexual interests that run
      counter to each other, setting the stage for sexually antagonistic coevolution,
      so that the various component parts of the male ejaculate-sperm, nutrients, anti
      aphrodisiacs, and gonadotrophic hormones-may each correspond to a separate
      conflict-cooperation balance between the sexes. Two scenarios for the evolution
      of nuptial gifts in butterflies are discussed, one arguing that variation in
      larval food is the underlying factor and the other arguing that sexually
      antagonistic coevolution is the driving force. The two views are complementary
      rather than mutually exclusive, although the former hypothesis predicts that
      variation in female mating rate depends on variation in larval food availability,
      whereas the latter suggests that variation in female mating rate between species
      results from species-specific idiosyncrasies.

PMID- 11506679
TI  - The descended larynx is not uniquely human.
AB  - Morphological modifications of vocal anatomy are widespread among vertebrates,
      and the investigation of the physiological mechanisms and adaptive functions of
      such variants is an important focus of research into the evolution of
      communication. The "descended larynx" of adult humans has traditionally been
      considered unique to our species, representing an adaptation for articulate
      speech, and debate concerning the position of the larynx in extinct hominids
      assumes that a lowered larynx is diagnostic of speech and language. Here, we use
      bioacoustic analyses of vocalizing animals, together with anatomical analyses of
      functional morphology, to document descended larynges in red and fallow deer. The
      resting position of the larynx in males of these species is similar to that in
      humans, and, during roaring, red-deer stags lower the larynx even further, to the
      sternum. These findings indicate that laryngeal descent is not uniquely human and
      has evolved at least twice in independent lineages. We suggest that laryngeal
      descent serves to elongate the vocal tract, allowing callers to exaggerate their
      perceived body size by decreasing vocal-tract resonant frequencies. Vocal-tract
      elongation is common in birds and is probably present in additional mammals. Size
      exaggeration provides a non-linguistic alternative hypothesis for the descent of
      the larynx in human evolution.

PMID- 11506680
TI  - A latent variable model of developmental instability in relation to men's sexual
      behaviour.
AB  - A single trait's fluctuating asymmetry (FA) is expected to be a poor measure of
      developmental instability. Hence, studies that examine associations between FA
      and outcomes expected to covary with developmental instability often have little
      power in detecting meaningful relationships. One way of increasing the power of
      detecting relationships between developmental instability and outcomes is through
      the use of multiple traits' FA. The way multiple traits have typically been used
      is in trait aggregates. Here, we illustrate another way of examining
      relationships with developmental instability using multiple traits' FA: through
      structural equation modelling. Covariances between measures of FA and an outcome
      variable are interpreted within the context of an explicit model of associations
      between variables, which is tested for fit and the parameters specified within
      the model are estimated. We used nine traits' FA as markers of a latent variable
      of men's developmental instability, which was associated with the number of
      sexual partners. The results indicate a sizeable correlation between
      developmental instability and men's sexual history, despite small correlations
      between individual traits' FA and sexual history.

PMID- 11506681
TI  - Pollination, seed set and seed predation on a landscape scale.
AB  - We analysed the combined effects of pollination and seed predation on seed set of
      Centaurea jacea in 15 landscapes differing in structural complexity. In the
      centre of each landscape, a patch of Centaurea plants was established for
      standardized measurements of flower visitation, seed predation and seed set. Both
      the number of flower-visiting bees and the proportion of flower heads damaged by
      seed predators increased with landscape complexity, which was measured as the
      proportion of semi-natural habitats. The mean number of seeds per flower head did
      not increase with the proportion of semi-natural habitats, presumably because of
      the counterbalancing effects of pollination and seed predation. For a subset of
      undamaged flower heads, the number of seeds per flower head was positively
      correlated with the number of flower visits. Further reasons for the unexpected
      failure to detect a correlation between landscape complexity and seed set
      appeared to be changes in flower-visitor behaviour and the contrasting responses
      of honeybees and wild bees to habitat context. Landscape analyses at eight
      spatial scales (radius of landscape sectors, 250-3000 m) showed that different
      groups perceived the landscape at different spatial scales. Changes in pollinator
      numbers could be explained only at small scales (up to 1000 m), while the seed
      predators also responded to large scales (up to 2500 m).

PMID- 11506682
TI  - Microstructural variation in conodont enamel is a functional adaptation.
AB  - Recognition that conodonts were the earliest vertebrate group to experiment with
      skeletal biomineralization provides a window in which to study the origin and
      early evolution of this developmental system. It has been contended that the
      conodont skeleton comprised a classic suite of vertebrate hard tissues, while
      others suggest that conodont hard tissues represent divergent specializations
      within the early diversification of vertebrate hard tissues, supporting a view
      that the hard tissues of conodonts, particularly enamel, exhibit a range of
      microstructural variation beyond that seen in vertebrates. New evidence reveals
      that, although variable, conodont enamel microstructure is consistent between
      homologous portions of homologous dentitions. Although there is a correlation
      between morphology and microstructure, this belies a stronger correlation between
      the commonality of microstructure and dental function. The enamel of conodonts
      evolved in response to changes in dental function and differentiation of the
      microstructural layer into a number of enamel types and can be linked to dental
      occlusion, heterodonty, a permanent dentition, enamel thickness and, probably
      above all, the small size of the dental elements.

PMID- 11506683
TI  - Carry-over effects of ultraviolet-B radiation on larval fitness in Rana
      temporaria.
AB  - A number of studies have failed to find evidence for negative effects of
      ultraviolet-B radiation (UVBR) on amphibian early-embryonic performance, leading
      to the conclusions, first, that the embryonic stages of many species are tolerant
      to UVBR, and second, that the increased amount of UVBR reaching the Earth's
      surface is not likely to have any direct negative effects on many amphibian
      populations. However, possible carry-over effects of exposure to UVBR in the
      embryonic stages to the larval stages have received less attention. We studied
      the effects of UVBR experienced during the embryonic stages (age less than 11
      days) on the later performance (age 11-75 days) of common frog, Rana temporaria,
      larvae. In a factorial laboratory experiment, newly fertilized embryos were
      divided into three different UVBR treatments (no UVBR (control), 1.25 kJm(-2)
      (normal) and 1.58 kJm(-2) (26% enhanced)), after which the individual larvae were
      raised until metamorphosis in the absence of UVBR. No effects of UVBR on
      embryonic survival rates, frequency of developmental anomalies or hatchling size
      were found, corroborating the earlier results indicating that R. temporaria
      embryos are tolerant to UVBR. However, analyses of larval performance revealed
      that larvae exposed to enhanced levels of UVBR as embryos suffered from an
      increased frequency of developmental anomalies and metamorphosed later and at a
      smaller size than larvae that had been protected from UVBR as embryos. These
      results suggest, in contrast to the earlier studies, that UVBR has direct
      negative effects on R. temporaria embryos, but these effects are expressed mostly
      or only during the later life stages. To this end, our results support the
      contention that carry-over effects from one life stage to another may be an
      important source of phenotypic variation in fitness.

PMID- 11506684
TI  - A test of whether rates of speciation were unusually high during the Cambrian
      radiation.
AB  - The Cambrian radiation represents an interval when nearly 20 animal phyla appear
      in the fossil record in a short geological time span; however, whether this
      radiation also represents a period of extremely rapid speciation remains unclear.
      Here, a stochastic framework is used to test the null hypothesis that diversity
      changes in one of the dominant Early Cambrian groups, the olenelloid trilobites,
      could be produced by tempos of speciation known to have operated during later
      time periods. Two continuous-time models, the Yule model and the birth and death
      process model, and one discrete-time model, the Bienayme-Galton-Watson branching
      process model, were used. No statistical evidence for uniquely high rates of
      speciation during the radiation in these trilobites was found when the continuous
      time models were used with low or moderate extinction rates, the rates typically
      associated with the Cambrian radiation, although the p values are fairly low or,
      in one case, significant when high extinction rates were used. However, rates of
      speciation were higher than the average Phanerozoic rates of speciation. The
      discrete-time model produced equivocal results: either rates were unusually high
      or the model is inapplicable during the Cambrian radiation. This suggests that
      there was nothing unique about evolutionary processes relating to the tempo of
      speciation during the Cambrian radiation.

PMID- 11506685
TI  - Local adaptation across a climatic gradient despite small effective population
      size in the rare sapphire rockcress.
AB  - When assigning conservation priorities in endangered species, two common
      management strategies seek to protect remnant populations that (i) are the most
      genetically divergent or (ii) possess the highest diversity at neutral genetic
      markers. These two approaches assume that variation in molecular markers reflects
      variation in ecologically important traits and ignore the possibility of local
      adaptation among populations that show little divergence or variation at marker
      loci. Using common garden experiments, we demonstrate that populations of the
      rare endemic plant Arabis fecunda are physiologically adapted to the local
      microclimate. Local adaptation occurs despite (i) the absence of divergence at
      almost all marker loci and (ii) very small effective population sizes, as
      evidenced by extremely low levels of allozyme and DNA sequence polymorphism. Our
      results provide empirical evidence that setting conservation priorities based
      exclusively on molecular marker diversity may lead to the loss of locally adapted
      populations.

PMID- 11506686
TI  - Arms races and the evolution of big fierce societies.
AB  - The causes of biological gigantism have received much attention, but only for
      individual organisms. What selection pressures might favour the evolution of
      gigantic societies? Here we consider the largest single-queen insect societies,
      those of the Old World army ant Dorylus, single colonies of which can have 20
      million workers. We propose that colony gigantism in Dorylus arises as a result
      of an arms race and test this prediction by developing a size-structured
      mathematical model. We use this model for exploring and potentially explaining
      differences in colony size, colony aggression and colony propagation strategies
      in populations of New World army ants Eciton and Old World army ants Dorylus. The
      model shows that, by determining evolutionarily stable strategies (ESSs),
      differences in the trophic levels at which these army ants live feed forwards
      into differences in their densities and collision rates and, hence, into
      different strategies of growth, aggression and propagation. The model predicts
      large colony size and the occurrence of battles and a colony-propagation strategy
      involving highly asymmetrical divisions in Dorylus and that Eciton colonies
      should be smaller, non-combative and exhibit equitable binary fission. These ESSs
      are in excellent agreement with field observations and demonstrate that
      gargantuan societies can arise through arms races.

PMID- 11506687
TI  - Competition between Eurasian red and introduced Eastern grey squirrels: the
      energetic significance of body-mass differences.
AB  - Daily energy expenditure (DEE) was measured in sympatric populations of red and
      grey squirrels using the doubly labelled water technique. Grey squirrels had
      significantly higher DEEs than red squirrels. However, the difference between the
      species was not separable from the effects of body mass on DEE. The DEEs of both
      species were in accordance with published allometric predictions incorporating
      body mass and ambient temperature. The differences in energetic requirements and
      social dominance, both consequences of body size, may represent means by which
      grey squirrels exert more interspecific competition on red squirrels than do
      conspecifics, potentially driving populations below viable levels in some sites.

PMID- 11506688
TI  - Epigenetic randomness, complexity and singularity of human iris patterns.
AB  - We investigated the randomness and uniqueness of human iris patterns by
      mathematically comparing 2.3 million different pairs of eye images. The phase
      structure of each iris pattern was extracted by demodulation with quadrature
      wavelets spanning several scales of analysis. The resulting distribution of phase
      sequence variation among different eyes was precisely binomial, revealing 244
      independent degrees of freedom. This amount of statistical variability
      corresponds to an entropy (information density) of about 3.2 bits mm(-2) over the
      iris. It implies that the probability of two different irides agreeing by chance
      in more than 70% of their phase sequence is about one in 7 billion. We also
      compared images of genetically identical irides, from the left and right eyes of
      324 persons, and from monozygotic twins. Their relative phase sequence variation
      generated the same statistical distribution as did unrelated eyes. This indicates
      that apart from overall form and colour, iris patterns are determined
      epigenetically by random events in the morphogenesis of this tissue. The
      resulting diversity, and the combinatorial complexity created by so many
      dimensions of random variation, mean that the failure of a simple test of
      statistical independence performed on iris patterns can serve as a reliable rapid
      basis for automatic personal identification.

PMID- 11506689
TI  - Reproductive changes in fluctuating house mouse populations in southeastern
      Australia.
AB  - House mice (Mus domesticus) in the Victorian mallee region of southeastern
      Australia show irregular outbreaks. Changes in reproductive output that could
      potentially drive changes in mouse numbers were assessed from 1982 to 2000.
      Litter size in females is positively correlated with body size. When standardized
      to an average size female, litter size changes seasonally from highest in spring
      to lowest in autumn and winter. Litter size is depressed throughout breeding
      seasons that begin when the abundance of mice is high, but is similar in breeding
      seasons over which the abundance of mice increases rapidly or remains low.
      Breeding begins early and is extended on average by about five weeks during
      seasons when mouse abundance increases rapidly. The size at which females begin
      to reproduce is larger during breeding seasons that begin when mouse abundance is
      high. An extended breeding season that begins early in spring is necessary for
      the generation of a house mouse plague, but it is not in itself sufficient.
      Reproductive changes in outbreaks of house mice in Australia are similar but not
      identical to reproductive changes that accompany rodent population increases in
      the Northern Hemisphere. We conclude that food quality, particularly protein, is
      a probable mechanism driving these reproductive changes, but experimental
      evidence for field populations is conflicting.

PMID- 11506690
TI  - A parasite that increases host lifespan.
AB  - Tenebrio molitor is an intermediate host for the rat tapeworm, Hymenolepis
      diminuta. Parasite oncospheres hatch in the beetle midgut and burrow through into
      the haemocoel, where they rapidly grow and mature into metacestodes. Repair of
      damage incurred during invasion and the nutritional demands of the parasites are
      likely to impose costs on the host. Despite these costs, there is an overall very
      highly significant difference in survival time (p < 0.001) between infected and
      control populations of beetles, with a hazard ratio of 2.35 (control versus
      infected). Infected females showed a 40% increase in survival time to 50%
      mortality and males showed a 25% increase in survival time to 50% mortality. This
      parasite-induced increase in host longevity is discussed in the light of changes
      in resource allocation that may occur in infected beetles. Previous findings have
      demonstrated that reproductive success is significantly reduced in infected
      females. The outcome of changes in the reproductive effort made by male beetles
      is less clear. We suggest that the optimum trade-off between reproduction and
      longevity may be altered to favour longer host survivorship, which is likely to
      enhance parasite transmission.

PMID- 11506691
TI  - Excitement in gene therapy!

PMID- 11506692
TI  - Independent contributions of GR-1+ leukocytes and Fas/FasL interactions to induce
      apoptosis following interleukin-12 gene therapy in a metastatic model of prostate
      cancer.
AB  - In a mouse model of prostate cancer, adenovirus-mediated interleukin-12 (Ad.mIL
      12) gene therapy resulted in significant growth inhibition of both the injected
      primary tumor and synchronous metastases. Within 2 days of vector injection, two
      distinct patterns of apoptosis were detected within the primary tumor, the
      inhibition of which with a caspase inhibitor substantially negated growth
      suppression. The dominant pattern displayed localized sheets of apoptotic cells
      in close association with necrosis containing polymorphic neutrophils (PMNs).
      Depletion of PMNs resulted in the loss of this pattern of apoptosis and reduced
      growth suppression. A second major wave of growth suppression within the primary
      tumor was mediated by an immune response. Natural killer (NK) cell activity was
      detected within tumor-infiltrating lymphocytes (TIL) by the eighth day post
      vector injection, the depletion of which resulted in a significant loss of
      survival enhancement. A more modest role for T cells was identified, which in the
      absence of documented cytotoxic T lymphocyte (CTL) activity may be related to a
      significant reduction in interferon-gamma (IFN-gamma) levels found in mice
      depleted of T cells, thereby reducing the secondary influences of IFN-gamma.
      However, depletion of NK cells or T cells had no discernible negative effect on
      IL-12-mediated anti-metastatic activity. Attention focused on the role of IFN
      gamma, observed following Ad.mIL-12 therapy, to mediate the diffuse pattern of
      apoptosis seen in the primary and metastatic lesions. In vitro studies noted the
      ability of IFN-gamma to up-regulate tumor cell expression of Fas and FasL to
      mediate apoptosis, whereas in vivo blockage of Fas/FasL interactions with soluble
      Fas resulted in a modest reduction in primary tumor growth suppression but
      complete abrogation within metastatic lesions.

PMID- 11506693
TI  - Transduction and apoptosis induction in the rat prostate, using adenovirus
      vectors.
AB  - Proapoptotic adenovirus vectors offer great promise for the treatment of cancer
      and nonmalignant conditions. Benign prostate hyperplasia (BPH) is a common
      nonmalignant enlargement of the prostate that involves epithelial, stromal, and
      smooth muscle components of the gland. We tested the hypothesis that an
      adenovirus vector expressing Fas ligand can be used to induce apoptosis in the
      prostate. We analyzed the efficiency of transduction and apoptosis induction in
      primary cultures of human prostate cells after adenovirus-mediated gene transfer.
      Efficient transduction was observed in primary prostate epithelial cells. Stromal
      and smooth muscle cells were more difficult to transduce, as no coxsackie
      adenovirus receptor (CAR) expression was detectable on these cells. However,
      transduction was achieved in these cells when the multiplicity of infection was
      increased to 100 focal-forming units per cell, or when the vectors were delivered
      as calcium phosphate precipitates. Infection of all three primary prostate cell
      types with an adenovirus vector that expresses Fas ligand (AdFasL/G) resulted in
      rapid apoptosis. Direct injection of the rat prostate with an adenovirus vector
      carrying luciferase resulted in substantial luciferase expression. TUNEL analysis
      demonstrated that AdFasL/G administration induced low-level apoptosis in
      prostatic epithelial cells throughout the gland. As a first step toward enhancing
      the efficiency of prostate transduction in vivo, we tested an adenovirus vector
      that was engineered to have an expanded tropism. This vector, AdZ.F2K(pK7), was
      10- to 500-fold more efficient than unmodified vectors in transducing prostate
      epithelial, smooth muscle, and stromal cells in culture. Moreover, AdZ.F2K(pK7)
      was more efficient than an unmodified vector at transducing the rat prostate in
      vivo, although the effect was dose dependent.

PMID- 11506694
TI  - In vivo transtracheal adenovirus-mediated transfer of human interleukin-10 gene
      to donor lungs ameliorates ischemia-reperfusion injury and improves early
      posttransplant graft function in the rat.
AB  - We examined the effect of adenovirus-mediated transtracheal transfer of the human
      interleukin 10 (hIL-10) gene on lung ischemia-reperfusion (IR) injury, which is
      the insult due to hypothermic preservation plus graft reperfusion, and
      posttransplant lung function in Lewis rat lungs. Thirty rats were divided into 6
      groups (n = 5). Groups 1 and 4 received 5 x 10(9) PFU of Ad5E1RSVhIL-10, groups 2
      and 5 received 5 x 10(9) PFU of Ad5BGL2 ("empty" vector), and groups 3 and 6
      received 3% sucrose (diluent). After 24 hr of in vivo transfection, lungs were
      stored at 4 degrees C (cold ischemic time, CIT) for 6 hr (groups 1-3) or 24 hr
      (groups 4-6) before transplantation. After 2 hr of reperfusion, lung function was
      assessed by oxygenation (FIO2, 1.0), airway pressure (AwP), and wet-to-dry (W/D)
      weight ratios. Rat tumor necrosis factor alpha (rTNF-alpha), interferon gamma
      (IFN-gamma), IL-10, and hIL-10 were measured in graft tissue and recipient plasma
      by ELISA and detected by immunohistochemistry (IHC). Partial pressure of oxygen
      (PaO2) levels in the hIL-10 group (6 hr of CIT) were higher than in empty vector
      and diluent groups (PaO2, 530 +/- 23 vs. 387 +/- 31 and 439 +/- 27 mmHg,
      respectively, p < 0.05). IL-10 rats after 24 hr of CIT showed higher PaO2 levels
      (260 +/- 29 mmHg) than empty vector (96 +/- 24 mmHg) or diluent (133 +/- 10 mmHg)
      lungs (p < 0.05). AwP and W/D ratios were reduced in hIL10 lungs (p < 0.05)
      compared with the other groups. rTNF-alpha and INF-gamma were reduced in tissue
      and plasma in groups 1 and 4 (p < 0.05). rIL-10 was reduced in the tissue of hIL
      10 lungs (p < 0.05). IHC showed equal distribution of cytokines in tissue and
      abundant transgene expression in large and small airway epithelium in hIL-10
      lungs.

PMID- 11506695
TI  - Baboon mesenchymal stem cells can be genetically modified to secrete human
      erythropoietin in vivo.
AB  - Human mesenchymal stem cells (MSCs) are capable of differentiating into multiple
      mesenchymal lineages including chondrocytes, osteocytes, adipocytes, and marrow
      stromal cells. Using a nonhuman primate model, we evaluated nonhuman primate MSCs
      as targets for gene therapy. Baboon MSCs (bMSCs) cultured from bone marrow
      aspirates appeared as a homogeneous population of spindle-shaped cells. bMSCs
      were capable of differentiating into adipocytes and osteocytes in vitro and
      chondrocytes in vivo. bMSCs were genetically modified with a bicistronic vector
      encoding the human erythropoietin (hEPO) gene and the green fluorescent protein
      (GFP) gene. Transduction efficiencies ranged from 72 to 99% after incubation of
      MSCs with retroviral supernatant. Transduced cells produced from 1.83 x 10(5) to
      7.12 x 10(5) mIU of hEPO per 10(6) cells per 24 hr in vitro before implantation.
      To determine the capacity of bMSCs to express hEPO in vivo, transduced bMSCs were
      injected intramuscularly in NOD/SCID mice. In a separate experiment, transduced
      bMSCs were loaded into immunoisolatory devices (IIDs) and surgically implanted
      into either autologous or allogeneic baboon recipients. Human EPO was detected in
      the serum of NOD/SCID mice for up to 28 days and in the serum of five baboons for
      between 9 and 137 days. NOD/SCID mice experienced sharp rises in hematocrit after
      intramuscular injection of hEPO-transduced bMSCs. The baboon that expressed hEPO
      for 137 days experienced a statistically significant (p < 0.04) rise in its
      hematocrit. These data demonstrate that nonhuman primate MSCs can be engineered
      to deliver a secreted and biologically active gene product. Therefore, human MSCs
      may be an effective target for future human gene therapy trials.

PMID- 11506696
TI  - In vivo analysis of intramuscular gene transfer in human subjects studied by on
      line ultrasound imaging.
AB  - The current study was designed to test the hypothesis that intramuscular (i.m.)
      injection of naked DNA leads to distribution of the injectate remote from the
      site of needle placement, a finding that might be expected to facilitate i.m.
      gene transfer. Transcutaneous ultrasound imaging was employed to monitor online
      the extent to which a solution of phVEGF165 was distributed among the skeletal
      musculature during 288 i.m. injections in 18 consecutive patients. In 237 (82.3%)
      of 288 muscle sites, the injection was performed into the distal calf muscle. In
      51 (17.7%) of 288 muscle sites, injection was performed into the first and/or
      second interosseous muscles of the dorsal foot. Unperturbed muscle was recognized
      by a characteristic echogenic, stippled texture that was bounded by more
      intensely echogenic fascia. When i.m. gene transfer was performed into the calf
      muscles, the injectate was distributed along a longitudinal dimension of 3.59 +/-
      0.79 cm (1.39-5.87 cm); the corresponding area of injectate measured by on-line
      planimetry was 1.83 +/- 0.51 cm2 (0.62-3.41 cm2). When i.m. gene transfer was
      performed into the interosseous muscles of the foot, the longitudinal extent of
      injectate distribution was 2.49 +/- 0.66 cm (1.61-3.91 cm), with a corresponding
      injectate area of 1.71 +/- 0.54 cm2 (0.51-2.86 cm2). These findings establish
      that a solution of plasmid DNA administered by direct i.m. injection into the
      skeletal muscles of the limb is distributed well beyond the site of needle entry.
      Thus, the use of multiple injections performed at different sites is likely to
      result in broad distribution of DNA injectate, a physical factor that may act to
      facilitate naked DNA and/or other gene transfer strategies.

PMID- 11506697
TI  - Sustainable systemic delivery via a single injection of lentivirus into human
      skin tissue.
AB  - The skin offers a tissue site accessible for delivery of gene-based therapeutics.
      To develop the capability for sustained systemic polypeptide delivery via
      cutaneous gene transfer, we generated and injected pseudotyped HIV-1 lentiviral
      vectors intradermally at a range of doses into human skin grafted on immune
      deficient mice. Unlike Moloney murine leukemia virus (MLV)-based retrovectors,
      which failed to achieve detectable cutaneous gene transfer by this approach,
      lentivectors effectively targeted all major cell types within human skin tissue,
      including fibroblasts, endothelial cells, keratinocytes, and macrophages. After a
      single injection, lentivectors encoding human erythropoietin (EPO) produced dose
      dependent increases in serum human EPO levels and hematocrit that increased
      rapidly within one month and remained stable subsequently. Delivered gene
      expression was confined locally at the injection site. Excision of engineered
      skin led to rapid and complete loss of human EPO in the bloodstream, confirming
      that systemic EPO delivery was entirely due to lentiviral targeting of cells
      within skin rather than via spread of the injected vector to visceral tissues.
      These findings indicate that the skin can sustain dosed systemic delivery of
      therapeutic polypeptides via direct lentivector injection and thus provide an
      accessible and reversible approach for gene-based delivery to the bloodstream.

PMID- 11506698
TI  - U.S. Department of Health and Human Services, National Institutes of Health.
      Recombinant DNA Advisory Committee: minutes of meeting, December 13 & 15, 2000.

PMID- 11506702
TI  - Ostip2, a novel oncoprotein that associates with the Rho exchange factor Ost.
AB  - The ost protooncogene encodes a guanine nucleotide exchange factor for the Rho
      family of small GTPases, RhoA and Cdc42. The N-terminal domain of Ost (Ost-N)
      appears to negatively regulate the oncogenic activity of the protein, as deletion
      of this domain drastically increases its transforming activity in NIH 3T3 cells.
      Using a yeast two-hybrid system, we identified five genes encoding proteins that
      can interact with Ost-N. One of them, designated OSTIP2 (Ost interacting protein
      2), encoded a previously uncharacterized protein. The OSTIP2 product is highly
      expressed in skeletal muscle as a 1.2-kb transcript. Full-length OSTIP2 cDNA
      contained an ORF of 193 amino acids. Transcription-coupled translation of OSTIP2
      cDNA in reticulocyte lysates revealed a protein product of 20 kDa, which
      corresponded to the predicted size of the protein. Bacterially expressed
      glutathione S-transferase (GST)-Ostip2 fusion protein efficiently associated in
      vitro with baculovirus-expressed Ost. Interestingly, expression of Ostip2 in NIH
      3T3 cells efficiently induced foci of morphologically transformed cells.
      Moreover, inoculation of athymic (nude) mice with OSTIP2 transfectants strongly
      induced tumor formation. These results suggest that Ostip2 is a novel oncoprotein
      that can interact with the Rho exchange factor Ost.

PMID- 11506703
TI  - Transcriptional regulation of the human mu opioid receptor (hMOR) gene: evidence
      of positive and negative cis-acting elements in the proximal promoter and
      presence of a distal promoter.
AB  - The mu opioid receptor (MOR), the primary binding site for morphine, is an
      important target for treating pain and drug addiction. The MOR gene is tightly
      regulated at the level of transcription, and potential polymorphisms in its 5'
      regulatory region can cause individual variation in MOR gene expression,
      nociception, and opiate responses. To study the 5' regulatory region of the human
      MOR gene (hMOR), we further investigated our previous finding of two regulatory
      regions and have localized a 40-bp positive cis-acting element and a 35-bp
      negative cis-acting element that regulate hMOR transcription in SK-N-SH cells.
      Electromobility shift assays and methylation interference assay with the 40-bp
      probe suggested that protein contacts were made with the core recognition
      sequence GCC (-510 to -508). The 35-bp sequence (-694 to -660) was the hMOR
      homolog of the mMOR negative regulatory element, and it suppressed proximal
      promoter activity of the hMOR gene. Additionally, the presence of an hMOR distal
      promoter was confirmed using RT-PCR. However, the activity of the distal promoter
      construct (-2325 to -777) was weak compared with the activity of the proximal
      promoter construct (-776 to -212).

PMID- 11506704
TI  - LZ-FYVE: a novel developmental stage-specific leucine zipper, FYVE-finger
      protein.
AB  - We describe the molecular cloning and characterization of LZ-FYVE, a novel
      embryonic factor that possesses two leucine zipper motifs and a FYVE-finger
      domain. A partial clone of LZ-FYVE, encoding a functional leucine zipper domain,
      was initially isolated from a mouse embryo cDNA library by virtue of its
      interaction in the yeast two-hybrid system with the transcription factor ATF-2.
      The LZ-FYVE protein demonstrated mouse embryo-specific expression by Northern
      blot analysis and was detected as a nuclear protein at very restricted periods
      (12--14 days post-coitus) in specific tissues during embryogenesis. In
      particular, LZ-FYVE protein was notable in embryonic lung, cartilage, and otic
      capsule. Structural analysis of the deduced, full-length LZ-FYVE amino acid
      sequence revealed two N-terminal leucine zipper domains as well as a C-terminal
      FYVE-finger domain. The FYVE-finger domains specifically recognized
      phosphatidylinositol 3-phosphate and have been previously described only in
      cytoplasmic proteins involved in endosomal membrane fusion, vesicular
      trafficking, or organelle-specific targeting. While LZ-FYVE may have endosomal
      functions in the cytoplasm, because LZ-FYVE is present in the nucleus at early
      stages of embryonic development, it is likely that LZ-FYVE has a nuclear
      function.

PMID- 11506705
TI  - The long form of CDK2 arises via alternative splicing and forms an active protein
      kinase with cyclins A and E.
AB  - We have reinvestigated the long form of cyclin-dependent kinase (CDK)2 that is
      expressed in many rodent cells. We show that the mRNA encoding CDK2L arises by
      alternative splicing and that the encoded protein can bind to, and be activated
      by, cyclins A and E. The complex of CDK2L with cyclin A has about half the
      specific activity of the equivalent CDK2-cyclin A complex. Also, CDK2L--cyclin A
      is inhibited to the same extent and by the same concentrations of p21(CIP1) as
      CDK2--cyclin A. The nucleotide sequences of intron V in the human and murine CDK2
      genes, where the sequences encoding the 48-residue insert in CDK2L are located,
      show very high conservation in the position of the alternatively spliced exon and
      its surroundings. Despite this, we were not able to detect significant expression
      of CDK2L in human cell lines, although a low level is expressed in COS-1 cells
      from monkeys.

PMID- 11506706
TI  - SAG/ROC2/Rbx2/Hrt2, a component of SCF E3 ubiquitin ligase: genomic structure, a
      splicing variant, and two family pseudogenes.
AB  - We have recently cloned and characterized an evolutionarily conserved gene,
      Sensitive to Apoptosis Gene (SAG), which encodes a redox-sensitive antioxidant
      protein that protects cells from apoptosis induced by redox agents. The SAG
      protein was later found to be the second family member of ROC/Rbx/Hrt, a
      component of the Skp1-cullin-F box protein (SCF) E3 ubiquitin ligase, being
      required for yeast growth and capable of promoting cell growth during serum
      starvation. Here, we report the genomic structure of the SAG gene that consists
      of four exons and three introns. We also report the characterization of a SAG
      splicing variant (SAG-v), that contains an additional exon (exon 2; 264 bp) not
      present in wildtype SAG. The inclusion of exon 2 disrupts the SAG ORF and gives
      rise to a protein of 108 amino acids that contains the first 59 amino acids
      identical to SAG and a 49-amino acid novel sequence at the C terminus. The entire
      RING-finger domain of SAG was not translated because of several inframe stop
      codons within the exon 2. The SAG-v protein was expressed in multiple human
      tissues as well as cell lines, but at a much lower level than wildtype SAG.
      Unlike SAG, SAG-v was not able to rescue yeast cells from lethality in a ySAG
      knockout, nor did it bind to cullin-1 or have ligase activity, probably because
      of the lack of the RING-finger domain. Finally, we report the identification of
      two SAG family pseudogenes, SAGP1 and SAGP2, that share 36% or 47% sequence
      identity with ROC1/Rbx1/Hrt1 and 30% or 88% with SAG, respectively. Both genes
      are intronless with two inframe stop codons.

PMID- 11506707
TI  - Distinctly different gene structure of KLK4/KLK-L1/prostase/ARM1 compared with
      other members of the kallikrein family: intracellular localization, alternative
      cDNA forms, and Regulation by multiple hormones.
AB  - The tissue kallikreins (KLKs) form a family of serine proteases that are involved
      in processing of polypeptide precursors and have important roles in a variety of
      physiologic and pathological processes. Common features of all tissue kallikrein
      genes identified to date in various species include a similar genomic
      organization of five exons, a conserved triad of amino acids for serine protease
      catalytic activity, and a signal peptide sequence encoded in the first exon.
      Here, we show that KLK4/KLK-L1/prostase/ARM1 (hereafter called KLK4) is the first
      significantly divergent member of the kallikrein family. The exon predicted to
      code for a signal peptide is absent in KLK4, which is likely to affect the
      function of the encoded protein. Green fluorescent protein (GFP)-tagged KLK4 has
      a distinct perinuclear localization, suggesting that its primary function is
      inside the cell, in contrast to the other tissue kallikreins characterized so far
      that have major extracellular functions. There are at least two differentially
      spliced, truncated variants of KLK4 that are either exclusively or predominantly
      localized to the nucleus when labeled with GFP. Furthermore, KLK4 expression is
      regulated by multiple hormones in prostate cancer cells and is deregulated in the
      androgen-independent phase of prostate cancer. These findings demonstrate that
      KLK4 is a unique member of the kallikrein family that may have a role in the
      progression of prostate cancer.

PMID- 11506726
TI  - Tissue-engineered fabrication of an osteochondral composite graft using rat bone
      marrow-derived mesenchymal stem cells.
AB  - This study tested the tissue engineering hypothesis that construction of an
      osteochondral composite graft could be accomplished using multipotent progenitor
      cells and phenotype-specific biomaterials. Rat bone marrow-derived mesenchymal
      stem cells (MSCs) were culture-expanded and separately stimulated with
      transforming growth factor-beta1 (TGF-beta1) for chondrogenic differentiation or
      with an osteogenic supplement (OS). MSCs exposed to TGF-beta1 were loaded into a
      sponge composed of a hyaluronan derivative (HYAF-11) for the construction of the
      cartilage component of the composite graft, and MSCs exposed to OS were loaded
      into a porous calcium phosphate ceramic component for bone formation. Cell-loaded
      HYAFF-11 sponge and ceramic were joined together with fibrin sealant, Tisseel, to
      form a composite osteochondral graft, which was then implanted into a
      subcutaneous pocket in syngeneic rats. Specimens were harvested at 3 and 6 weeks
      after implantation, examined with histology for morphologic features, and stained
      immunohistochemically for type I, II, and X collagen. The two-component composite
      graft remained as an integrated unit after in vivo implantation and histologic
      processing. Fibrocartilage was observed in the sponge, and bone was detected in
      the ceramic component. Observations with polarized light indicated continuity of
      collagen fibers between the ceramic and HYAFF-11 components in the 6-week
      specimens. Type I collagen was identified in the neo-tissue in both sponge and
      ceramic, and type II collagen in the fibrocartilage, especially the pericellular
      matrix of cells in the sponge. These data suggest that the construction of a
      tissue-engineered composite osteochondral graft is possible with MSCs and
      different biomaterials and bioactive factors that support either chondrogenic or
      osteogenic differentiation.

PMID- 11506727
TI  - Influence of rhBMP-2 on rat bone marrow stromal cells cultured on titanium fiber
      mesh.
AB  - Titanium (Ti) fiber mesh is a candidate scaffold material for the creation of
      bone graft substitutes (BGS). Two densities (3.54 x 10(4) cells/cm(2) [LD or low
      density] and 3.54 x 10(5) cells/cm(2) [HD or high density]) of rat bone marrow
      stromal cells were seeded on Ti-fiber mesh discs. Cells were cultured for up to
      16 days, 7 days of which the cells were in the presence of various concentrations
      of rhBMP-2 (0, 10, 100, and 1,000 ng/mL) in order to evaluate osteogenic
      expression. Scanning electron microscopy (SEM), light microscopy (LM), energy
      dispersive spectroscopy (EDS), DNA and calcium (Ca) content measurements, and x
      ray diffraction (XRD) analysis were performed. SEM and EDS evaluation showed that
      a confluent layer of cells was present on top of the meshes together with
      collagen bundles and calcified globular accretions. Light microscopical
      evaluation showed a densely stained layer in the upper part of the mesh. SEM and
      Ca content measurement showed that calcification starts at 8 days. In addition,
      it was demonstrated that DNA content peaked at 8 days. LM, SEM, and Ca content
      evaluation revealed positive effects of increasing the cell seeding density, the
      rhBMP-2 concentration and the culture time on mineralization. Increasing the cell
      seeding density also showed a positive effect on DNA content. No effects of rhBMP
      2 concentration were seen on DNA content. Finally, XRD revealed that the
      deposited matrix contained a precipitate of a stable calcium phosphate phase. We
      conclude that (1) titanium fiber mesh sustains excellent osteogenic expression in
      vitro, (2) increasing the cell seeding density has a positive effect on
      osteogenic expression in titanium mesh in vitro, and (3) in high density
      specimens, rhBMP-2 concentrations of 100 ng/mL and 1,000 ng/mL stimulate
      extracellular matrix calcification in a dose-responsive manner.

PMID- 11506728
TI  - Expression of liver-specific functions by rat hepatocytes seeded in treated
      poly(lactic-co-glycolic) acid biodegradable foams.
AB  - Techniques of liver replacement would benefit patients awaiting donor livers and
      may be a substitute for transplantation in patients whose livers can regenerate.
      Poly(lactic-co-glycolic acid) (PLGA) copolymers are biodegradable and have been
      shown to be useful as scaffolds for seeding and culturing various types of cells.
      In this study, foam disks were prepared from PLGA (lactic-to-glycolic mole ratio
      of 85:15) by lyophilization of benzene (5% w/v) solutions. These disks were then
      used as scaffolds for rat hepatocyte culture. Foams were coated with either a
      type I collagen gel (0.1% w/v), coated with gelatin (5% w/v), or treated with
      oxygen plasma (25 W, 90 s) to modify their surface chemistry and wettability. The
      disks were then seeded with rat hepatocytes (10(6)/mL) and cultured for a period
      of 2 weeks. All surface treatments resulted in increased hydrophilicity, the
      greatest being obtained by collagen treatment (contact angle < 10 degrees ), and
      a minimal decrease in void fraction (5%). DNA content after a 2-week culture
      period increased proportionally with the wettability of the treated foam surface.
      Urea synthesis in untreated foams averaged 15.3 +/- 2.3 microg/h/microg DNA,
      which was significantly higher than that for controls, whereas gelatin and
      collagen treated foams exhibited urea synthetic rates below the control levels at
      all times. The DNA content decreased significantly by about 50% between days 1
      and 12. PLGA foams, treated and untreated, represent a promising scaffold for
      scaling up hepatocyte cultures.

PMID- 11506729
TI  - Autologous primary muscle-derived cells transfer into the lower urinary tract.
AB  - The goal of these experiments was to establish the basic methodology for future
      clinical applications of muscle-derived cells (MDC) tissue engineering and gene
      transfer for the treatment of urological dysfunction. Primary MDC isolated via
      preplating techniques from adult female SD rats were transduced with retrovirus
      encoding the expression of beta-galactosidase reporter gene. The MDC were
      injected into the right and left lateral walls of the bladder and proximal
      urethra of the autologous animals (n = 6) with a 10 microl Hamilton micro
      syringe. The amount of injected MDC ranged from 1 to 2 x 10(6) cells. The
      injected tissue was harvested after 7, 14, and 28 days, sectioned and examined
      histologically for beta-galactosidase and immunohistochemically for fast myosin
      heavy chain specific to skeletal muscle. The tissues were also stained for anti
      CD4 and anti-CD8 antibodies to assess for cellular immune reaction. We have
      detected a large number of autologous MDC expressing beta-galactosidase and
      positively stained for fast myosin heavy chain in the bladder and urethral wall.
      Many injected myoblasts and myotubes were also seen in the bladder and urethral
      wall at each time point. Staining of lymphocytes with anti-CD4 and anti-CD8
      antibodies was negative after MDC injection at each time point. We have
      demonstrated the long-term survival of autologous MDC and MDC mediated gene
      transfer into the bladder and urethral wall. Autologous MDC and MDC mediated gene
      transfer may be a promising treatment to augment bladder and urethral sphincter
      function.

PMID- 11506730
TI  - Using HSV-thymidine kinase for safety in an allogeneic salivary graft cell line.
AB  - Extreme salivary hypofunction is a result of tissue damage caused by irradiation
      therapy for cancer in the head and neck region. Unfortunately, there is no
      currently satisfactory treatment for this condition that affects up to 40,000
      people in the United States every year. As a novel approach to managing this
      problem, we are attempting to develop an orally implantable, fluid-secreting
      device (an artificial salivary gland). We are using the well-studied HSG salivary
      cell line as a potential allogeneic graft cell for this device. One drawback of
      using a cell line is the potential for malignant transformation. If such an
      untoward response occurred, the device could be removed. However, in the event
      that any HSG cells escaped, we wished to provide additional patient protection.
      Accordingly, we have engineered HSG cells with a hybrid adeno-retroviral vector,
      AdLTR.CMV-tk, to express the herpes simplex virus thymidine kinase (HSV-tk)
      suicide gene as a novel safety factor. Cells were grown on plastic plates or on
      poly-L-lactic acid disks and then transduced with different multiplicities of
      infection (MOIs) of the hybrid vector. Thereafter, various concentrations of
      ganciclovir (GCV) were added, and cell viability was tested. Transduced HSG cells
      expressed HSV-tk and were sensitive to GCV treatment. Maximal effects were seen
      at a MOI of 10 with 50 microM of GCV, achieving 95% cell killing on the poly-L
      lactic acid substrate. These results suggest that engineering the expression of a
      suicide gene in an allogeneic graft cell may provide additional safety for use in
      an artificial salivary gland device.

PMID- 11506731
TI  - Development of composite cultured oral mucosa utilizing collagen sponge matrix
      and contracted collagen gel: a preliminary study for clinical applications.
AB  - A new type of cultured mucosa was developed as a mucosal substitute. This
      composite cultured oral mucosa (CCOM) was composed of (1) a lamina propria in
      which fibroblasts were embedded in contacted collagen gel and honeycomb
      structured collagen sponge and (2) stratified epithelial cell layers on the
      surface of the cultured lamina propria. CCOM had a well-stratified and
      differentiated epithelial cell layer, and its involucrin and laminin expression
      resembled that of normal oral mucosa. Desmosomes were recognizable with
      transmission electron microscopic examination. In the lamina propria, contracted
      collagen gel had pooled away from the sponge wall, leaving a sparse structure
      inside the collagen sponge. Transplantation of CCOM to nude mice was performed by
      creating full-thickness wound and then applying CCOM (n = 12). Murine skin
      allograft (n = 4) and no-graft conditions (n = 5) served as controls. The mice
      were sacrificed for histological evaluation and assessed for wound contraction 28
      days after transplantation. The epithelium of the CCOM-treated group had five to
      10 cell layers, and the dermis contained many fibroblasts and a large amount of
      collagen bundles. The wound contraction of the CCOM-treated group was
      statistically less than that of the no-graft group. These results indicate that
      CCOM has barrier functions against various stresses and can induce a
      fibrovascular ingrowth from the surrounding wound bed, and that CCOM could be
      applied in a clinical setting.

PMID- 11506732
TI  - Tissue-engineered vascular autograft: inferior vena cava replacement in a dog
      model.
AB  - Tissue-engineered vascular autografts (TEVAs) were made by seeding 4-6 x 10(6) of
      mixed cells obtained from femoral veins of mongrel dogs onto tube-shaped
      biodegradable polymer scaffolds composed of a polyglycolid acid (PGA) nonwoven
      fabric sheet and a copolymer of L-lactide and caprolactone (n = 4). After 7 days,
      the inferior vena cavas (IVCs) of the same dogs were replaced with TEVAs. After
      3, 4, 5, and 6 months, angiographies were performed, and the dogs were
      sacrificed. The implanted TEVAs were examined both grossly and
      immunohistologically. The implanted TEVAs showed no evidence of stenosis or
      dilatation. No thrombus was found inside the TEVAs, even without any
      anticoagulation therapy. Remnants of the polymer scaffolds were not observed in
      all specimens, and the overall gross appearance similar to that of native IVCs.
      Immunohistological staining revealed the presence of factor VIII positive
      nucleated cells at the luminal surface of the TEVAs. In addition, lesions were
      observed where alpha-smooth muscle actin and desmin positive cells existed.
      Implanted TEVAs contained a sufficient amount of extracellular matrix, and showed
      neither occlusion nor aneurysmal formation. In addition, endothelial cells were
      found to line the luminal surface of each TEVA. These results strongly suggest
      that "ideal" venous grafts with antithrombogenicity can be produced.

PMID- 11506733
TI  - Evaluation of ultra-thin poly(epsilon-caprolactone) films for tissue-engineered
      skin.
AB  - Various natural and synthetic polymeric materials have been used as scaffold
      matrices for tissue-engineered skin. However, the commercially available skin
      replacement products pose problems of poor mechanical properties and
      immunological rejection. We have thus developed a film of 5 microm thickness, via
      biaxial stretching of poly(epsilon-caprolactone) (PCL), as a potential matrix for
      living skin replacements. The aim of this study was to evaluate the feasibility
      of using biaxially stretched PCL films as matrices for culturing human dermal
      fibroblasts. For this purpose, we cultured human dermal fibroblasts for 7 days on
      the films. Glass cover slips and polyurethane (PU) sheets were used as controls.
      The data from phase contrast light, confocal laser, and scanning electron
      microscopy suggested that biaxially stretched PCL films support the attachment
      and proliferation of human dermal fibroblasts. Thymidine-labeling results showed
      quantitatively that cell proliferation on the PCL films was superior to that on
      the PU samples. These results indicated that biaxially stretched PCL films
      supported the growth of human dermal fibroblasts and might have potential to be
      applied in tissue engineering a dermal equivalent or skin graft.

PMID- 11506734
TI  - In vitro characterization of an artificial dermal scaffold.
AB  - The treatment of extensive burn injuries has been enhanced by the development of
      artificial skin substitutes. Integra Artificial Skin, an acellular collagen
      glycosaminoglycan (C-GAG) dermal equivalent requires a two-stage grafting
      procedure. However, preseeding the C-GAG dermal equivalent with cultured
      fibroblasts and keratinocytes, with the aim of performing a single-stage grafting
      procedure, may be beneficial in terms of replacing the requirement for
      traditional split-skin grafts. In this comparative in vitro study, the
      interactions of cultured human dermal fibroblasts and epidermal keratinocytes in
      Integra Artificial Skin in comparison to cadaver deepidermalized dermis (DED) was
      investigated. An increase in cell proliferation and migration in the C-GAG dermal
      equivalent was observed over time. Cocultures of fibroblasts and keratinocytes on
      both dermal equivalents showed positive expression of proliferation,
      differentiation, and extracellular matrix (ECM) protein markers. Organization of
      keratinocytes in the epidermal layers of DED composites were better compared to
      the C-GAG composites. Deposition of ECM proteins was enhanced in the presence of
      keratinocytes in both dermal equivalents. Results demonstrate that in vitro the C
      GAG dermal equivalent is biocompatible for cell attachment, migration,
      proliferation, and differentiation. Preseeding Integra Artificial Skin with
      cultured autologous fibroblasts and keratinocytes for in vivo application, as a
      single-stage grafting procedure, warrants testing. A better clinical outcome may
      be achieved as shown by our in vitro results of the coculture composites.

PMID- 11506735
TI  - Thermo-responsive culture dishes allow the intact harvest of multilayered
      keratinocyte sheets without dispase by reducing temperature.
AB  - To develop new technology for harvesting transplantable cultured epithelium
      without dispase treatment, human keratinocytes were plated on culture dishes
      grafted with a thermo-responsive polymer, poly(N-isopropylacrylamide). The
      grafted dish surfaces are slightly hydrophobic above 32 degrees C, but reversibly
      change to hydrophilic below this temperature. According to the method of
      Rheinwald and Green, keratinocytes proliferated and made a multilayer on the
      grafted surfaces at 37 degrees C, as on the nongrafted culture dishes. The
      multilayered keratinocyte sheets were detached from the grafted surfaces only by
      reducing temperature to 20 degrees C without need for dispase. No cell remnants
      were observed on the dishes. Such cell sheet detachment was not observed on
      nongrafted dishes. Immunoblotting of harvested keratinocyte sheets revealed that
      dispase treatment disrupted E-cadherin and laminin 5, while these molecules
      remained intact in the keratinocyte sheets harvested by only reducing temperature
      from the grafted dishes. Transmission electron microscopy revealed that
      desmosomes were destroyed in dispase treatment but retained in low-temperature
      treatment. Use of thermo-responsive dishes was examined as a new tool for tissue
      engineering to achieve the preparation of artificial epithelium for cell
      transplantation as well as for the investigation of intact multilayered
      keratinocyte sheets.

PMID- 11506736
TI  - Publication of U.S. patents.

PMID- 11506738
TI  - Seven days of low-dose orally administered murine type I interferon does not
      cause priming in vivo.
AB  - In vivo, low-dose orally administered type I interferon (LDOA IFN) therapy has
      been shown to provide beneficial effects in a number of diseases. These diseases
      vary in nature (viral, autoimmune, and neoplastic), yet LDOA IFN therapy is able
      to provide effective treatment. Despite the growing knowledge of the efficacy of
      such treatment and ongoing human clinical trials, the mechanism by which LDOA IFN
      acts remains largely unknown. In this study, we examined the phenomenon known as
      "priming" as a potential mechanism by which LDOA IFN effects may be mediated.
      Priming is a phenomenon in which pretreatment of cells or entire organisms with
      type I IFN causes significantly enhanced IFN production after induction of the
      endogenous IFN system by virus or polyI:C. This phenomenon of priming has been
      exploited in commercial industry for the mass production of type I IFN for
      medical and research use. It was found that LDOA IFN treatment did not cause
      priming in vivo.

PMID- 11506737
TI  - Interleukin-12 p40/p70 ratio and in vivo responsiveness to IFN-alpha treatment in
      chronic hepatitis C.
AB  - To evaluate the relationship between cytokine balance and responsiveness to
      interferon-alpha (IFN-alpha), we investigated the production of IFN-gamma,
      interleukin-10 (IL-10), IL-12 p70, and IL-12 p40 by peripheral blood mononuclear
      cell (PBMC) cultures from patients with chronic hepatitis C (CHC) before and
      after 1 year of IFN-alpha treatment. Before the therapy, responder (R) patients
      exhibited lower IFN-gamma release, higher IL-10 production, and higher values of
      the IL12 p40/p70 ratio compared with nonresponders (NR). Increased sensitivity to
      the effects of IL-12 and IL-10, as well as higher IL-12-dependent IFN-gamma
      secretion, were also found in the R subset. After IFN-alpha therapy, an increase
      in IFN-gamma production and a decrease in the IL-12 p40/p70 ratio were observed
      in R patients, whereas opposite results were obtained in the NR group. Finally,
      the therapy induced downregulation of IL-10 production and cell responsiveness to
      recombinant IL-12 in all patients. These findings imply that predominance of a T
      helper 2 (Th2) cytokine profile in CHC patients favors the beneficial effects of
      IFN-alpha, thus suggesting a therapeutic role for Th1-driven stimulation of
      immune response. The findings also stress the primary importance of the IL-12 p40
      and p70 balance in the modulation of immune responses to hepatitis C virus (HCV).

PMID- 11506739
TI  - Myasthenia gravis during low-dose IFN-alpha therapy for chronic hepatitis C.
AB  - We describe the case of a 56-year-old man who had high aminotransferase levels
      and anti-hepatitis C virus (HCV) antibodies. He underwent liver biopsy and
      biochemical screening to evaluate whether he would benefit from interferon (IFN)
      treatment. The patient was discharged with a diagnosis of HCV-related active
      chronic hepatitis, skin porphyria, and type 2 diabetes. On December 5, 1995, he
      began therapy with recombinant IFN-alpha at a dose of 3 MIU three times a week.
      He stopped this therapy in February 1996 because of asthenia, diplopia, headache,
      and anxiety. During IFN therapy, he had normal aminotransferase levels and no
      detectable HCV RNA, a condition that persists to the present. Between March and
      May 1996, the patient was admitted several times to a neurology clinic, where
      myasthenia gravis was diagnosed and treatment with pyridostigmine and
      cyclosporine was initiated. This case and others indicate that caution should be
      exercised in administering IFN because low doses can be correlated with
      myasthenia gravis in patients without malignancies.

PMID- 11506740
TI  - Zinc potentiates the antiviral action of human IFN-alpha tenfold.
AB  - During the last decade, various zinc salts have been used against the common cold
      syndrome, which is known to be initiated by respiratory viruses, particularly
      rhinoviruses. Using rhinovirus as the challenge virus, we investigated whether
      zinc salts (Zn) could potentiate the antiviral action of native human leukocyte
      interferon (HuIFN-alpha) and rHuIFN-gamma. We found that HuIFN-alpha was
      potentiated tenfold at rather low levels of IFN activity (0.6-0.8 U/ml),
      resulting in 100% protection. Zn alone gave only marginal protection, if any. In
      contrast to HuIFN-alpha, rHuIFN-gamma directly increased the cytopathic effect of
      rhinovirus at low levels (<2 U/ml) but protected the cells at higher IFN levels
      (5-20 U/ml). No potentiation was seen with Zn. HuIFN-beta protected against
      rhinovirus at the same doses as used with HuIFN-alpha, but in contrast to HuIFN
      alpha, no potentiation was noted.

PMID- 11506741
TI  - Local intratumoral tumor necrosis factor-alpha and systemic IFN-alpha 2b in
      patients with locally advanced prostate cancer.
AB  - To examine tolerability and activity of local, intratumoral tumor necrosis factor
      alpha (TNF-alpha) and systemic interferon-alpha2b (IFN-alpha2b) in locally
      advanced, hormone-resistant prostate cancer (LA-HRPC), 10 patients with LA-HRPC
      (T4N x M0, n = 3, T4N x M1, n = 5; T4N1M1, n = 2) were treated with recombinant
      TNF-alpha injected locally into prostate tumor tissue at 4-week intervals
      (maximum of four cycles) combined with intermittent subcutaneous (s.c.)
      administration of 5 x 10(6) IU IFN-alpha2b. Twenty-nine TNF-alpha cycles were
      administered. Despite significant TNF-alpha leakage into the systemic circulation
      2 h after intraprostatic application (from a mean of 9 to a mean of 416 pg/ml; p
      = 0.0034), TNF-alpha (and IFN-alpha2b) was well tolerated (WHO grade 1-2
      toxicity), possibly because of its rapid neutralization by increasing soluble 55
      kDa and 75-kDa TNF receptor levels in the serum (mean increase 268% and 91%,
      respectively) at the same time. TNF-alpha induced prostate tumor cell necrosis in
      all patients, leading to a significant reduction of prostate volume in 9 of 10
      cases (mean 38%; p = 0.0025). The significant short-term increase of prostate
      specific antigen (PSA) (mean 65%; p < 0.001), tissue polypeptide-specific antigen
      (TPS) (mean 85%; p = 0.001), and possibly interleukin-8 (IL-8) (mean 2687%; p <
      0.009) serum levels within 4 h after TNF-alpha confirmed the cytotoxic effect in
      vivo. In the long term, serum PSA levels dropped by 18%-87%, reaching the nadir
      value 7 weeks after baseline. Objective responses of metastases were not seen.
      Intraprostatic administration of TNF-alpha is feasible at a tolerable toxicity in
      patients with LA-HRPC and, thus, may be a new treatment option for these
      patients.

PMID- 11506742
TI  - IFN-gamma inhibits lipopolysaccharide-induced interleukin-1 beta in primary
      murine macrophages via a Stat1-dependent pathway.
AB  - Interleukin-1 (IL-1) plays an important role in host defenses against microbial
      pathogens. Excessive production of this cytokine, however, may be responsible in
      part for the lethality observed during sepsis. Our studies show that interferon
      gamma (IFN-gamma) downregulates lipopolysaccharide (LPS)-induced interleukin
      1beta (IL-1beta) transcription in primary macrophages. This phenomenon does not
      occur in splenocytes or bone marrow-derived macrophages from signal transducer
      and activator of transcription (Stat1)-deficient mice, suggesting that Stat1, a
      transcription factor involved in IFN signaling, plays a critical role in this
      process. Moreover, nitric oxide (NO) was also involved in the downregulation of
      LPS-induced IL-1 by IFN, as addition of the inducible nitric oxide synthase
      (iNOS) inhibitor L-N(6)-(1-iminoethyl)lysine (NIL) negated the effect. Kinetic
      analysis of IL-1 and IFN levels in LPS-treated mice in vivo suggests that IFN
      mediated inhibition of IL-1 might be an important negative feedback mechanism for
      limiting IL-1 generation in vivo.

PMID- 11506743
TI  - Human monocyte-derived dendritic cells produce bioactive gelatinase B: inhibition
      by IFN-beta.
AB  - We studied the secretion of gelatinase B by dendritic cells (DC) generated by
      culturing human peripheral blood monocytes in granulocyte-macrophage colony
      stimulating factor (GM-CSF) and interleukin-4 (IL-4). First, we found the
      intracellular expression of gelatinase B on sections of fixed DC pellets.
      Zymography analysis of the supernatants of DC cultured for 72 h demonstrated the
      presence of gelatinase B. To determine if DC produce net enzymatic activity,
      bioactive gelatinase, a novel sensitive fluorescent-activated substrate
      conversion (FASC) assay was used to complement the zymography data. Culture media
      of unstimulated DC demonstrated reproducible net gelatinolytic activity. Tumor
      necrosis factor-alpha (TNF-alpha) IL-1beta but not lipopolysaccharide (LPS)
      stimulation caused a significant increase in gelatinase B production in
      zymography analysis. Both types of stimulation failed to increase net gelatinase
      activity in FASC assay. Interestingly, interferon-beta (IFN-beta) significantly
      diminished both the total zymolytic production and the net bioactive gelatinase
      produced by DC in a dose-dependent manner. We conclude that human monocyte
      derived DC secrete bioactive gelatinase B and that IFN-beta inhibits this
      production.

PMID- 11506744
TI  - Identification of IFN-gamma-producing CD4+ T cells following PMA stimulation.
AB  - Treatment of T cells with phorbol esters, such as phorbol myristate acetate
      (PMA), induces downregulation of CD4, making unambiguous identification of this
      subset difficult. In this study, the kinetics of intracellular expression of
      interferon-gamma (IFN-gamma) and downmodulation of surface CD4 were measured in
      peripheral blood mononuclear cells (PBMC) after PMA stimulation. The number of
      IFN-gamma-producing cells increased within a 4-h period while the fluorescence
      intensity of the CD4(+) cell population decreased, and the two phenomena were
      correlated (n = 9; p = 0.01). Our data suggest that intracellular staining of CD4
      together with cytokine staining will make identification of CD4(+) cells possible
      and facilitate the procedure of intracellular staining of cytokines.

PMID- 11506745
TI  - Cytokines and cell surface receptors as target end points of immunosuppression
      with cyclosporine A.
AB  - Targets of cyclosporine (CsA) were identified from an array of stimulated
      lymphocyte responses (sLR) comprising 34 stimulation conditions in whole blood
      from 3 normal human volunteers (NHV) containing clinically relevant CsA
      concentrations (0-1200 ng/ml) in vitro. In whole blood from 5 additional NHV,
      selected targets (intracellular interleukin-2 [IL-2], tumor-necrosis factor-alpha
      [TNF-alpha], and interferon-gamma [IFN-gamma]) were measured in phorbol myristate
      acetate (PMA)-ionomycin-stimulated T lymphocytes. Effect:concentration
      relationships were analyzed with E(max) pharmacodynamic (PD) equations and
      expressed as the concentration associated with one-half maximal inhibitory effect
      (EC(50)). CsA demonstrated a rich matrix of inhibitory effects on T cells
      (CD3(+)), B cells (CD19(+)), dendritic cells (DC) (CD11c(+)), and basophils
      (CD123(+)) but not on monocytes (CD14(+)) (n = 3). PD analyses suggested that the
      EC(50) of CsA (1) for IL-2 in CD3(+) cells in NHV (n = 8) was similar to the
      EC(50) demonstrated by us previously in CD4(+) cells from transplanted patients
      (n = 13) (EC(50) = 260 ng/ml vs. 249 ng/ml), (2) for each cytokine was different
      under identical stimulation conditions (TNF-alpha, 324 ng/ml; IFN-gamma, 504
      ng/ml), and (3) was relatively constant for a given cytokine under different
      stimulation conditions (e.g., PMA-ionomycin or the staphylococcal enterotoxin B
      [SEB] superantigen). In conclusion, inhibition of cytokine targets by CsA is
      concentration dependent. Further, a given CsA concentration may produce similar
      inhibitory effects across different stimulation conditions. Measurement of
      cytokine target expression may, therefore, allow effect-controlled administration
      of CsA during clinical transplantation.

PMID- 11506746
TI  - Alterations in the expression of interleukin-2R subunits by activated T cells
      from elderly humans are uncoupled from aberrancies in G1/S progression.
AB  - Activated T cells from elderly humans are known to often display a decline in
      interleukin-2 (IL-2) production. However, the possible effects of aging on the
      expression of IL-2 receptor (IL-2R) subunits by human T cells are more
      controversial and less well characterized. In the present investigation, the
      surface expression of IL-2Ralpha, IL-2Rbeta, and IL-2Rgamma subunits on resting
      and activated T cells from 15 sets of elderly and young humans was evaluated. The
      results showed no significant differences in the average expression of IL
      2Ralpha, IL2Rbeta, and IL-2Rgamma on resting T cells from elderly and young
      subjects, with values of 10% or less. Similarly, no significant differences were
      found in the mean levels of IL-2Ralpha, IL-2Rbeta, and IL-2Rgamma on T cells from
      elderly and young subjects stimulated with anti-Ig cross-linked anti-CD3
      (monoclonal antibody [mAb] OKT3), phorbol myristate acetate (PMA), anti-CD3 and
      PMA, or 1% phytohemagglutinin (PHA) plus PMA. Analyses of the expression of IL-2R
      on activated T cells from elderly people revealed a marked heterogeneity in IL2R
      levels irrespective of the stimuli. Other experiments showed that the age-related
      alterations in surface expression of IL-2Ralpha were not correlated to changes in
      the release of soluble IL-2Ralpha. Age-related changes in IL-2R expression on
      activated T cells from individual donors were not coupled to the ability of the T
      cells to undergo G(1)/S progression. Collectively, these observations suggest
      that activated T cells from elderly people exhibit substantial heterogeneity in
      the expression of IL-2R subunits and that alterations in IL-2R expression may be
      distinct from intrinsic defects in G(1)/S progression and proliferative
      responses.

PMID- 11506747
TI  - Antiproliferative effects of IFN-alpha correlate with the downregulation of
      nuclear factor-kappa B in human Burkitt lymphoma Daudi cells.
AB  - Interferon-alpha (IFN-alpha) is known to exhibit antiviral, antiproliferative,
      and immunomodulatory properties through mechanisms still not fully understood.
      Nuclear transcription factor-kappaB (NF-kappaB) plays a major role in viral
      replication, cell proliferation, and immune response. Whether antiproliferative
      effects of IFN are mediated through suppression of NF-kappaB is not known. We,
      therefore, examined the relationship between the antiproliferative effects of IFN
      alpha and NF-kappaB activity in a human Burkitt lymphoma Daudi cell line. These
      cells were found to constitutively express high levels of active NF-kappaB that
      cannot be further activated by tumor necrosis factor (TNF). Treatment of cells
      with IFN-alpha suppressed the activated NF-kappaB in a dose-dependent manner,
      with an optimum effect at 10 U/ml in 72 h. Suppression of NF-kappaB correlated
      with a concomitant decrease in the cytoplasmic levels of IkappaBalpha, the
      inhibitory protein of NF-kappaB, known to be regulated by NF-kappaB.
      Downregulation of constitutive NF-kappaB activity correlated with a decrease in
      cell proliferation by IFN-alpha. Overall, our results suggest that IFN-alpha is a
      potent suppressor of constitutive NF-kappaB, which may contribute to the
      inhibition of cell proliferation.

PMID- 11506748
TI  - Regulation of interleukin-8 expression by nitric oxide in human pancreatic
      adenocarcinoma.
AB  - The regulation of interleukin-8 (IL-8) expression by nitric oxide (NO) was
      determined in human pancreatic cancer cell lines. CaPan-2 and FG human pancreatic
      adenocarcinoma cells were incubated for 24 h in medium alone or medium containing
      a cytokine mixture in the presence or absence of an NO synthase (NOS) inhibitor,
      N(G)-monomethyl-L-arginine (NMA). The NOS activity and level of IL-8 expression
      were determined. IL-8 expression was induced in the two cell lines. A low level
      of NOS activity was detectable only in CaPan-2 cells. Moreover, the presence of
      NMA did not reverse the induction of IL-8. The FG cells were then engineered to
      produce a physiologic level of NO and incubated in medium alone or medium
      containing 1 mM NMA. No significant IL-8 expression was induced in those
      producing a low level of NO, whereas IL-8 expression was induced in those
      producing a high level of NO. Inhibition of NO production by NMA reversed this
      effect. Incubation of FG cells with an NO donor, S-nitroso-D,L.-acetyl
      penicillamine (SNAP), led to a concentration-dependent and time-dependent
      induction of IL-8 expression. This NO-mediated upregulation of IL-8 expression
      correlated with an increase in IL-8 gene transcription and mRNA stability. Our
      results indicate that NO is involved in the regulation of IL-8 expression in and
      contributes to the progression of human pancreatic cancer.

PMID- 11506750
TI  - Nomenclature of avian interferon proteins.

PMID- 11506749
TI  - Efficacy and safety of orally/sublingually, intranasally, and intraperitoneally
      administered recombinant murine interferon in the treatment of murine
      encephalomyocarditis virus.
AB  - Interferons (IFN) have been shown to be effective in protecting animals against
      lethal viral infections when administered systemically in relatively high doses.
      Intraperitoneal (i.p.) injection of mice with encephalomyocarditis virus (EMCV)
      gives rise to a rapidly progressive fatal disease characterized by central
      nervous system involvement and encephalitis. IFN-alpha has been shown to be
      effective in protecting mice against lethal EMCV infection when given via
      parenteral and oral/sublingual routes. The current study was designed to explore
      the ability of orally/sublingually and intranasally (i.n.) administered IFN-alpha
      to treat mice infected with EMCV in support of a planned clinical trial to
      evaluate efficacy of oral IFN-alpha in human viral infections. The primary
      objective of the study was to determine the efficacy of recombinant murine IFN
      alpha (rMuIFN-alpha) in the treatment of mice infected with 100 LD(50) EMCV
      following oral, i.n., and i.p. administration at doses of 20,000 and 100,000 IU.
      The results of the current experiment did not indicate protection from infection
      with EMCV in mice that received IFN by the i.n. or oral/sublingual routes. The
      negative controls, infection of mice with 100 LD(50) of EMCV followed by
      treatment with excipient via all three routes, resulted in death of nearly all
      mice, as expected. The positive control, treatment of EMCV-infected (100 LD(50))
      mice with rMuIFN-alpha via the i.p. route, was successful in protecting a
      significant number of mice from death compared with matched controls. This study
      points out the need to determine the optimum conditions for administration of
      oral/sublingual or i.n. IFN to insure maximum efficacy against viral infections.

PMID- 11506752
TI  - The telemedicine network of the People's Liberation Army.
AB  - In the early 1990s, the People's Liberation Army began to establish a
      telemedicine network for the non-emergency health-care of the personnel of
      military units and their families, as well as local civilian patients. All data
      were transferred over the ordinary telephone network. All the stations were
      uniformly equipped with PCs containing videoconferencing cards. The network
      comprised 13 management centres and 208 teleconsultation stations. To evaluate
      the telemedicine service, we conducted a survey with written questionnaires and
      telephone interviews. The questionnaire was sent to the person responsible for
      each telemedicine station. A total of 187 questionnaires were returned, a
      response rate of 85%. The survey showed that 1503 teleconsultation sessions had
      been conducted for military as well as civilian patients during the 18-month
      study period, and 1708 static images had been transferred across the network
      during these sessions.

PMID- 11506753
TI  - Teledermatology as a tool for communication between general practitioners and
      dermatologists.
AB  - A feasibility study of teledermatology was undertaken in Groningen. Six general
      practitioners (GPs) sent digital images by email, along with relevant patient
      information, to dermatologists at the Martini Ziekenhuis Groningen, a general non
      academic hospital. The dermatologists returned their responses by email. A total
      of 89 cases were dealt with in this way. On average, the GPs took three
      photographs per patient. The time taken by the GP to produce and transmit the
      images, and to implement the telemedicine advice received from the dermatologist,
      was 9 min and 3 min, respectively. The time spent on diagnosis, provision of
      advice and response by email amounted to 10 min for the dermatologist. It was
      concluded that teleconsultations by email are feasible in the daily practice of
      GPs and dermatologists in a general non-academic hospital. Generally, GPs,
      dermatologists and patients were satisfied with teleconsultations. Furthermore,
      GPs reported that 63% of the teleconsultations were of educational value.

PMID- 11506754
TI  - The potential of telemedicine for home nursing in Queensland.
AB  - The potential for telemedicine in home nursing was examined by retrospectively
      reviewing the case-notes relating to home visits made by nurses in Queensland.
      The case-notes of 166 clients were randomly selected from 10 domiciliary nursing
      centres run by the Blue Care nursing organization in south-east Queensland. Two
      experienced community registered nurses independently undertook a retrospective
      review of the case-notes. Each reviewer made an independent judgement as to
      whether any of the home nursing visits in the episode of care could have been
      conducted by telemedicine. Visits requiring hands-on care were deemed to be
      unsuitable for telemedicine. A total of 12,630 home visits were reviewed. The
      median number of visits per client was 27 (range 1-722). The mean age of the
      clients was 72 years (range 2-93 years). A total of 1521 home visits (12%) were
      judged suitable for telemedicine. There was no significant difference in
      suitability between males (13%) and females (12%). Care interventions suitable
      for telemedicine were more likely to be those of a supportive, educational or
      review nature. Forty per cent of clients lived up to 5 km from the home nursing
      centre, 33% lived 5-10 km from the centre and 27% lived over 10 km from the
      centre. The results of the present study confirm the potential for telemedicine
      in home nursing in Australia.

PMID- 11506756
TI  - Telemedical work and cooperation.
AB  - In telemedicine, cooperation occurs via telecommunication. This represents a new
      situation for medical cooperation. Whether such cooperation works poorly or well
      will be important with an increasing volume of telemedicine. When personnel are
      involved in external cooperation, as in telemedicine, the question of cooperation
      within one's own organization also arises. To investigate these matters,
      qualitative interviews were performed with 30 persons working in teledermatology,
      telepsychiatry, a telepathology frozen-section service and tele-otolaryngology.
      The results showed that cooperating by telecommunication mainly worked well. The
      cooperation may be influenced by factors such as personality, knowing each other
      personally, preparation and experience. Telemedical teamwork may be improved by
      factors like experience and education. Working with telemedicine did not reduce
      the personnel's cooperation within their own organizations, but rather improved
      it, although this effect was slight and most commonly involved improved knowledge
      of others. In general, the findings concerning cooperation and telemedicine were
      positive.

PMID- 11506755
TI  - Patient and physician satisfaction in a clinical study of telemedicine in a
      hypertensive patient population.
AB  - We studied patient and physician satisfaction with telemedicine for the care of a
      hypertensive population. Once recruited, participants were seen both in person
      and via telemedicine (in random order) on the same day. After each meeting,
      patient and physician satisfaction surveys were completed. In the 12-month study,
      there were 107 pairs of visits. The physicians reported a small but significant
      increase in workload, mental effort, technical skills and visit duration for
      telemedicine when compared with face-to-face consultations. They noted that the
      telemedicine system worked well in the majority of cases and could reduce the
      need for future treatment. Patients reported slightly but significantly higher
      satisfaction scores for the following for in-person than for telemedicine
      meetings: technical quality, interpersonal care and time spent. Patients reported
      high satisfaction scores for both telemedicine and in-person visits.

PMID- 11506757
TI  - Clinical effectiveness and cost analysis of patient referral by videoconferencing
      in orthopaedics.
AB  - The clinical effectiveness and costs of videoconferencing in orthopaedics between
      primary and secondary care were examined in an eight-month prospective,
      comparative study. The general surgery outpatient clinics of two Finnish district
      hospitals were compared: Peijas Hospital, with telemedicine, and Hyvinkaa
      Hospital, without it. The three study primary-care centres referred a total of
      419 adult patients to the outpatient clinics. The population-based number of
      referrals to Peijas Hospital was similar to that to Hyvinkaa Hospital after
      adjusting for the proportion of older people living in the Hyvinkaa Hospital
      municipalities. Of the 225 patients referred to Peijas Hospital, 168 (75%) were
      given appointments at the outpatient clinic of surgery and the rest of the
      referred patients received a teleconsultation. All patients referred to Hyvinkaa
      Hospital were given appointments at the outpatient clinic. The direct costs of an
      outpatient visit were 45% greater per patient than for a teleconsultation, with a
      marginal cost decrease of EU48 for every new teleconsultation. A cost
      minimization analysis of the alternative interventions showed a net benefit of
      EU2500 in favour of teleconsultations. The use of videoconferencing between
      primary and secondary care was modest in orthopaedics, although the use of this
      telemedicine method was shown to reduce direct costs and be cost-effective.

PMID- 11506758
TI  - A cost-minimization analysis of oncology home care versus hospital care.
AB  - We compared the costs of patient care for two groups of 10 oncology patients. The
      test group was treated at home and had access to 24 h telephone support, and the
      control group was treated in hospital, either as inpatients or as outpatients.
      Direct variable costs were provided by health insurance companies. The time
      invested by the health-care staff was recorded. The amount of time devoted to
      patients was more uniform in hospital than in the patients' homes, which suggests
      that patients at home received a less generic, more specific form of care. The
      nurses spent four times as long caring for home care patients as for hospital
      patients. The total cost of home care was 64% of that of hospital care, although
      this difference was not significant. The mean daily costs were three times lower
      at home than in hospital. All direct costs, except laboratory tests, were lower
      at home. Pharmaceutical costs were six times lower at home. Telephone support for
      home oncology care was cost saving and avoided 27 nursing home visits, which
      represented 35 working hours and Pta270,000 in savings to the health insurance
      companies.

PMID- 11506759
TI  - A cost-minimization analysis of the societal costs of realtime teledermatology
      compared with conventional care: results from a randomized controlled trial in
      New Zealand.
AB  - A randomized controlled trial was carried out to measure the societal costs of
      realtime teledermatology compared with those of conventional hospital care in New
      Zealand. Two rural health centres were linked to a specialist hospital via ISDN
      at 128 kbit/s. Over 10 months, 203 patients were referred for a specialist
      dermatological consultation and 26 were followed up, giving a total of 229
      consultations. Fifty-four per cent were randomized to the teledermatology
      consultation and 46% to the conventional hospital consultation. A cost
      minimization analysis was used to calculate the total costs of both types of
      dermatological consultation. The total cost of the 123 teledermatology
      consultations was NZ$34,346 and the total cost of the 106 conventional hospital
      consultations was NZ$30,081. The average societal cost of the teledermatology
      consultation was therefore NZ$279.23 compared with NZ$283.79 for the conventional
      hospital consultation. The marginal cost of seeing an additional patient was
      NZ$135 via teledermatology and NZ$284 via conventional hospital appointment. From
      a societal viewpoint, and assuming an equal outcome, teledermatology was a more
      cost-efficient use of resources than conventional hospital care.

PMID- 11506761
TI  - Online patient information.

PMID- 11506760
TI  - Eighteen months' experience with remote diagnosis, management and education in
      congenital heart disease.
AB  - In July 1998, a telemedicine link was established between the Venizelio General
      Hospital in Crete and the Paediatric Cardiology Department of the Aghia Sophia
      Children's Hospital in Athens. The telemedicine link used ISDN at 384 kbit/s for
      diagnosis, management and education in congenital heart disease. Over 18 months,
      a total of 39 teleconsultations were carried out, concerning 93 children with
      haemodynamically significant cardiac abnormalities. Forty-four children (47%)
      were managed locally after teleconsultation, while three children with
      transposition of the great arteries (3%) were transported as emergency cases to
      Athens in the first days of life. The other 46 children (50%) had a scheduled
      appointment at a tertiary centre for cardiac catheterization, angiocardiography,
      operative treatment or surgical repair. The telemedicine link brought a number of
      benefits, such as better access to the tertiary centre and the avoidance of
      patient transportation.

PMID- 11506762
TI  - What's new in Nicotine & Tobacco Research?

PMID- 11506763
TI  - Introduction: Tobacco treatment outcome methodology papers - a series.

PMID- 11506764
TI  - Statistical analysis of randomized trials in tobacco treatment: longitudinal
      designs with dichotomous outcome.
AB  - This article considers two important issues in the statistical treatment of data
      from tobacco-treatment clinical trials: (1) data analysis strategies for
      longitudinal studies and (2) treatment of missing data. With respect to data
      analysis strategies, methods are classified as 'time-naive' or longitudinal. Time
      naive methods include tests of proportions and logistic regression. Longitudinal
      methods include Generalized Estimating Equations and Generalized Linear Mixed
      Models. It is concluded that, despite some advantages accruing to 'time-naive'
      methods, in most situations, longitudinal methods are preferable. Longitudinal
      methods allow direct effects of the tests of time and the interaction of
      treatment with time, and allow model estimates based on all available data. The
      discussion of missing data strategies examines problems accruing to complete-case
      analysis, last observation carried forward, mean substitution approaches, and
      coding participants with missing data as using tobacco. Distinctions between
      different cases of missing data are reviewed. It is concluded that optimal
      missing data analysis strategies include a careful description of reasons for
      data being missing, along with use of either pattern mixture or selection
      modeling. A standardized method for reporting missing data is proposed. Reference
      and software programs for both data analysis strategies and handling of missing
      data are presented.

PMID- 11506765
TI  - Neuronal nicotinic receptors: from structure to function.
AB  - Molecular identification of the genes and resulting protein sequences for a large
      number of nicotinic acetylcholine receptor (nAChR) subunits has stimulated
      numerous studies highlighting their role in several human behaviors including
      neurological disorders and nicotine addiction. This receptor gene family is
      likely to be involved in release of multiple neurotransmitters in both brain and
      periphery that mediate sensitivity and tolerance to nicotine. Recent findings
      also suggest that alterations in these receptors may lead to neurological
      diseases, some associated with increased incidence of smoking. This review
      addresses current knowledge of nicotinic receptor structure, regulation of
      expression, and function, in both normal and psychiatric subjects.

PMID- 11506766
TI  - The relationship between tobacco use, substance-use disorders and mental health:
      results from the National Survey of Mental Health and Well-being.
AB  - AIMS: To examine comorbidity between tobacco use, substance-use disorders and
      mental health problems among Australian adults aged 18 years and over. METHOD:
      Data from the 1997 Australian National Survey of Mental Health and Well-being
      were analyzed. This survey was a stratified, multistage probability sample of
      10,641 adults, representative of the Australian population. Univariate
      associations between tobacco use, substance use and mental health were examined,
      and then multivariate analyses were conducted to control for demographic
      characteristics, neuroticism, and other drug use. MEASUREMENTS: Tobacco use
      status was defined as: never smoker, former smoker and current smoker. DSM-IV
      diagnoses of substance use, anxiety, and affective disorders were derived using
      the Composite International Diagnostic Interview (CIDI). Other measures included
      a screener for psychosis and measures of psychological distress and disability.
      FINDINGS: Current tobacco use was strongly associated with abuse/dependence upon
      alcohol, cannabis, and other substances, and with higher rates of anxiety and
      affective disorders. Current smokers were more likely to screen positively for
      psychosis and reported greater psychological distress and disability than non
      smokers and never smokers. These higher rates of other problems were not
      explained by differences in demographic characteristics, neuroticism scores, or
      by other drug use. Former smokers did not have higher rates of affective or
      anxiety disorders; however, they had higher rates of alcohol-use disorders, and
      of cannabis-use disorders after adjusting for covariates. CONCLUSIONS: Current
      tobacco use is associated with a range of other substance-use and mental health
      problems. These are likely to reduce the success of attempts to quit smoking. The
      presence of these other problems needs to be considered when considering smoking
      cessation treatment, and further research may provide information on more
      effective treatment strategies for persons with co-existing substance-use and
      mental health problems.

PMID- 11506767
TI  - Temporal analysis of the relationship of smoking behavior and urges to mood
      states in men versus women.
AB  - Epidemiological investigations of mood and smoking have relied largely on
      retrospective self-reports, with little research on real-time associations. We
      examined the relationship of mood states to contemporaneous smoking urges and to
      subsequent smoking and also assessed the effects of smoking on subsequent mood.
      For 2 days, 25 female and 35 male smokers aged 18-42 made three prompted diary
      entries per hour plus pre- and post-smoking entries (6882 entries). Data were
      analyzed with generalized estimating equations. We found significant positive
      associations between smoking urge and anger, anxiety, and alertness in women and
      men; fatigue in men only; sadness more strongly in men than women; and happiness
      in women only. Decreased alertness and increased anxiety predicted subsequent
      smoking in men only. Smoking was followed by decreased anger levels in men and
      women and decreased sadness in men only. In men with lower overall anger
      episodes, increased anger was associated with subsequent increased smoking. These
      findings suggest that smoking is related to negative affect and energy level,
      more clearly in men, and has palliative effects on sadness in men and on anger in
      men and women. These data demonstrate that ambulatory research can reveal targets
      for early intervention and smoking cessation.

PMID- 11506768
TI  - Effect of smoking reduction and cessation on cardiovascular risk factors.
AB  - This open study examined the effect of smoking reduction and smoking cessation on
      established cardiovascular risk factors. Fifty-eight healthy adult smokers
      (smoking >or=15 cigarettes/day for at least 3 years) were provided with nicotine
      nasal spray (to be used ad libitum) and asked to stop smoking. The primary goal
      during the first 8 weeks, however, was to reduce their daily smoking by at least
      50%. Subjects were then followed for another 8 weeks; at this point, 33
      participants had successfully stopped smoking. Cardiovascular risk factors
      including fibrinogen, hemoglobin, hematocrit, triglycerides, and cholesterol were
      measured at baseline and at 9 and 17 weeks. After 8 weeks of smoking reduction,
      the mean number of cigarettes smoked per day had decreased from 21.5 +/- 0.6
      (baseline) to 10.8 +/- 0.6 (p < 0.001). This was accompanied by significant
      improvements in fibrinogen (from 2.9 +/- 0.1 g/l at baseline to 2.6 +/- 0.1 g/l,
      p = 0.011), white blood cells (from 7.0 +/- 0.4 to 6.2 +/- 0.3 x 10(9)/l, p =
      0.005) and the high-density/low-density lipoprotein (HDL/LDL) ratio (0.33 +/-
      0.03 to 0.37 +/- 0.03, p < 0.005). Following 8 weeks of abstinence from smoking,
      the mean white blood cell count was further reduced (to 6.1 +/- 0.3 x 10(9)/l, p
      = 0.026 vs. baseline) and there were also significant improvements in HDL (from
      1.16 +/- 0.06 mmol/l at baseline to 1.32 +/- 0.06, p < 0.001) and LDL (from 3.78
      +/- 0.16 mmol/l at baseline to 3.52 +/- 0.17, p = 0.015). In conclusion, 8 weeks
      of smoking reduction resulted in clinically significant improvements in
      established cardiovascular risk factors. These improvements were even greater
      after an additional period of abstinence from smoking.

PMID- 11506769
TI  - Is nicotine dependence related to smokers' support for restrictions on smoking?
AB  - OBJECTIVES: To examine the relationship between nicotine dependence and
      attitudes, predicted behaviours and support regarding restrictions on smoking.
      DESIGN: Population-based, computer-assisted, telephone survey of adults in
      Ontario, Canada using a two-stage stratified sampling design; 1764 interviews
      were completed (65% response rate) yielding 424 (24%) cigarette smokers, of whom
      354 (83%) smoked daily. The Heaviness of Smoking Index was used as a measure of
      nicotine dependence. MAIN OUTCOME MEASURE: Attitudes toward smoking restrictions,
      predicted compliance with more restrictions, and support for total smoking bans.
      RESULTS: Attitudes favorable to smoking restrictions tended to decrease with
      increased nicotine dependence, but the associations were not statistically
      significant after adjusting for demographic variables. Predicted compliance with
      more restrictions on smoking decreased with higher levels of dependence, as did
      support for a total ban on smoking in restaurants, workplaces, bingo halls, and
      hockey arenas. Support for smoking bans in food courts, family fast food
      restaurants, and bars and taverns did not vary significantly with level of
      nicotine dependence. CONCLUSIONS: Level of nicotine dependence is associated with
      intended behaviors and support for smoking restrictions in some settings. These
      results have implications for tobacco control programs and policies.

PMID- 11506770
TI  - Breaking down boundaries in nicotine and tobacco research. Seventh Annual Meeting
      Society for Research on Nicotine and Tobacco, Seattle, WA, USA. 23-25 March 2001.

PMID- 11506772
TI  - Multiple organ failure in septic patients.
AB  - Multiple organ failure (MOF) is the main cause of death in ICUs, especially
      affecting septic patients. It is strongly related to number of systems with
      failure, type of system involved, risk factors such as age, previous chronic
      diseases, delayed or inadequate resuscitation, persistent infection, immune
      suppression, and others. The prognoses is worse for patients rather than in
      elective or emergency surgical patients. The objective of this article is to
      provide data from our university teaching hospital ICU related to the incidence
      of septic patients, the distribution of MOF, and distribution of failure among
      each of the organs. The mortality rate, relationship between mortality and age,
      and mortality and types of organs affected were evaluated. The main bacterial
      causes of sepsis were also identified. A retrospective evaluation was done of 249
      patients admitted to the ICU in a 4 month period during 1999. Fifty four patients
      had sepsis diagnosed by ACCS/SCCM criteria. There were 37 men and 17 women; 24
      medical and 30 post-surgical patients (9 after elective surgery and 21 emergency
      patients). APACHE II score was calculated on admission and MOF, measured for the
      first five days, was diagnosed using Marshall and Meakins criteria. The
      statistical method used was non-parametric Mann-Whitney test, p<0.05 was
      considered significant. The incidence of sepsis was recorded in 54/249 patients
      (22%). Thirty of these 54 patients (56%) died. Death occurred in 2 of 11 patients
      with one organ failure (18%), in 14/27 with 2 or 3 organ failures (52%), and
      14/16 with 4 or more organ failures (88%). None of the three patients 15 to 20
      years old died, 17/32 (55%) patients age 21-60 years, and >61 years 13/19 (68%),
      died. There were 23 patients with positive bacterial culture. The most frequent
      bacteria found were: Pseudomonas aeruginosa (5), multiresistant Acinetobacter
      baumanii (3), Staphylococcus epidermidis (3), Enterobacter aerogenes (3),
      Klebsiella pneumoniae (2) and multiresistant Staphylococcus aureus (2). The mean
      value +/- SD of APACHE II (mortality risk) for survivors was 21 +/- 18 and for
      non-survivors 42 +/- 26 (p<0.001). We conclude that MOF due to sepsis in an ICU
      is frequent, with high mortality related to the number of failing organs, age and
      high APACHE II.

PMID- 11506773
TI  - High prevalence of hepatitis C infection in a Brazilian prison: identification of
      risk factors for infection.
AB  - Hepatitis C virus (HCV) causes infectious hepatitis worldwide. It is transmitted
      mainly by blood products and sharing of intravenous paraphernalia during illicit
      drug use. High prevalence rates have been described among specific groups
      considered to be at higher risk for HCV infection, including prison inmates. The
      objectives of this study were: to determine the HCV seroprevalence among inmates
      of Casa de Detencao de Sao Paulo; to identify risk factors for HCV infection; and
      to compare the seroprevalence of HCV to other blood borne or sexually transmitted
      diseases. From December, 1993, to January, 1994, a total of 779 inmates were
      interviewed to collect information on sociodemographic status, sexual behavior,
      and past experience with illicit drugs. Blood samples were obtained from 756
      inmates for serological tests. 310 (41%) blood samples were positive for anti
      HCV, 425 (56.2%) were negative, and 21 (2.8%) showed indeterminate results. In
      this population, we found a seroprevalence of 13.7% for HIV, 3.3% for syphilis
      (VDRL), and 68.1% for hepatitis B virus previous infection. Four variables were
      each identified as associated with a positive anti-HCV serologic test: a positive
      VDRL (OR = 2.63 IC 95% 1.08 to 6.36); a time of current imprisonment longer than
      130 months (OR = 2.44 IC 95% 1.04 to 5.71); previous incarceration at Casa de
      Detencao de Sao Paulo (OR = 1.73 IC 95% 1.19 to 2.52) and; illicit drug use
      before admission to the Casa de Detencao de Sao Paulo (OR = 1.64 IC 95% 1.15 to
      2.33). The seroprevalence of HCV antibodies among the study population was high
      (41%), indeed, one of the highest clusters of HCV infection recorded until now.
      Four variables were each shown to be associated with HCV infection. The
      simultaneous presence of these 4 variables is associated with an 82% probability
      of being anti-HCV positive. Although risk factor analysis indicates most HCV
      infections occur prior to inprisonment, initiation of control measures to prevent
      continued transmission after incarceration should be done.

PMID- 11506774
TI  - The prevalence of enteropathy due to strongyloidiasis in Puerto Maldonado
      (Peruvian Amazon).
AB  - Human strongyloidiasis is an important health problem in the southeast region of
      Peruvian Amazon, due to its prevalence and long term morbidity. An
      epidemiological study was conducted in the Peruvian Amazon area of Puerto
      Maldonado to determine the prevalence of strongyloidiasis in the population.
      Stool samples were collected from 1,133 patients at the outpatient department of
      our clinic. Strongyloidiasis affected 221 examined patients (20%). Prevalence was
      highest in males, mostly in children and elderly men. People living in urban and
      marginal urban areas, those coming from outside the region, and Andean people,
      showed the highest prevalences. Pre-school children were more likely to be
      parasitized than older children. The most common symptoms were diarrhea (55%),
      abdominal pain (32%) and cough (53%). One in 7 (13%) affected patients presented
      with moderate or severe symptoms, including life-threatening complications. Other
      intestinal parasites were found frequently in patients diagnosed with
      strongyloidiasis. Improved human waste disposal services are considered to be the
      main requirement to reduce the high prevalence of this disease.

PMID- 11506775
TI  - Treatment of nosocomial pneumonia: an experience with meropenem.
AB  - This study aimed at evaluating the efficacy and safety of meropenem as first
      choice treatment for nosocomial pneumonia (NP) in intensive care units (ICU) in
      Hospital das Clinicas (HC) - University of Sao Paulo; a hospital with high
      incidence of antimicrobial resistance. Prospective, open, and non-comparative
      trial with meropenem were done in patients with ventilator-associated or
      aspiration NP in 2 ICUs at HC - University of Sao Paulo. Etiologic investigation
      was done through bronchoalveolar lavage and blood cultures prior to study entry.
      Twenty-five (25) critically ill patients with NP were enrolled (mean age 40
      years). Ventilator-acquired pneumonia was responsible for 76% of cases and
      aspiration NP for 24%. Specific etiologic agents were identified and considered
      to be clinically and temporally responsible for NP in 11 (44%) patients. A.
      baumanii was responsible for 6 cases (55%), P. aeruginosa for 3 (27%), and S.
      aureus for 2 (18%). At completion of treatment, 19 patients (76%) showed either
      cure (48%) or improvement (28%) after use of meropenem therapy. Mortality was 12%
      at the end of therapy (8% after excluding 1 non-evaluable patient). After 4 to 6
      weeks of follow-up, 12 (48%) patients had improved or been totally cured, and
      overall mortality was 24%. Clinical complications were observed in 11 patients
      (44%), with none of them definitely related to the study drug. Meropenem as
      monotherapy was effective and well-tolerated in most NP patients in our ICU. The
      low mortality rate in this study might have been due to first choice use of this
      drug. Controlled, drug comparative clinical trials are needed to support this
      preliminary observation.

PMID- 11506776
TI  - In vitro antimicrobial activity of the aminoglycoside arbekacin tested against
      oxacillin-resistant Staphylococcus aureus isolated in Brazilian hospitals.
AB  - Arbekacin is an aminoglycoside used in Japan for treating infections caused by
      gentamicin and oxacillin-resistant S. aureus (ORSA). The objective of this study
      was to determine the in vitro antimicrobial activity of arbekacin against 454
      clinical isolates of ORSA. The isolates were consecutively collected between
      January and July, 2000, from patients hospitalized in 8 Brazilian medical
      centers. The antimicrobial susceptibility testing was performed by disk diffusion
      method according to NCCLS recommendations. The vast majority of the isolates, 453
      strains (99.8%), were considered susceptible to arbekacin based on the criteria
      proposed by the Requirements for Antibiotic Products of Japan. Only 1 isolate
      (0.2%) was classified as resistant. On the other hand, high rates of resistance
      were demonstrated for other aminoglycosides, such as gentamicin (97.6%
      resistance) and amikacin (97.0% resistance). Resistance rate was also high for
      ciprofloxacin (98.0%). All isolates were considered susceptible to vancomycin.
      The excellent in vitro antimicrobial activity of arbekacin demonstrated in this
      study indicates that this antimicrobial agent may play an important role in the
      treatment of severe ORSA infections, especially those that show poor clinical
      response with vancomycin monotherapy. Since the aminoglycosides should not be
      used as monotherapy to treat Gram positive infections, further studies evaluating
      in vitro and in vivo synergistic activity of arbekacin combinations are necessary
      to clarify the clinical role of this aminoglycoside.

PMID- 11506777
TI  - Comparative study of bacterial infection prevalence between cirrhotic patients
      with and without upper gastrointestinal bleeding.
AB  - Bacterial infection is a frequent complication in patients with chronic liver
      disease, mainly during the advanced stages. There is evidence that the main
      factors that contribute to a predisposition to infection in cirrhotic patients
      are related to hepatic failure with consequent immunodeficiency. Invasive
      procedures (diagnostic or therapeutic) can predispose to bacterial infections,
      and upper gastrointestinal bleeding (UGB) is considered a potentially important
      risk factor. A group of cirrhotic patients (child B and C Pugh groups) were
      evaluated retrospectively by chart reviews regarding the prevalence of bacterial
      infection during hospitalization to determine whether UGB was a risk factor. An
      infection was considered present if a specific organ system was identified or if
      fever (> 38(o)C) persisted for more than 24 hours with associated leukocytosis.
      Spontaneous bacterial peritonitis was based on classical criteria. Eighty-nine
      patients were evaluated. Fourty-six patients presented with UGB, and 43 patients
      had no UGB (control). There were infections recorded in 25/46 (54%) patients with
      UGB, and 15/43 (35%) in those without UGB (p=0.065). The ratio of the number of
      infections/admitted patients, was significantly larger in the group with UGB
      (0.78 +/- 0.89 vs. 0.39 +/- 0.62; p=0.028) since patients had more than one
      infection. In the UGB group compared to non UGB group, ascites was more frequent
      (67% vs. 42%; p=0.027); they were more likely to have undergone endoscopic
      procedures (p<0.001) and the mean +/- SD for platelets count was smaller (96,114
      +/- 57,563 vs 145,674 +/- 104,083; p=0.007). The results show that UGB is an
      important contribution to bacterial infection among Child B and C cirrhotic
      patients.

PMID- 11506778
TI  - Expression of class 5 antigens by meningococcal strains obtained from patients in
      Brazil and evaluation of two new monoclonal antibodies.
AB  - Determining the profile of antigen expression among meningococci is important for
      epidemiologic surveillance and vaccine development. To this end, two new mouse
      monoclonal antibodies (MAbs) have been derived against Neisseria meningitidis
      proteins (class 5). The MAbs were reactive against outer membrane antigens and
      were bactericidal. Selected anti-class 5 MAbs [(5.1)-3E6-2; (5.3)-3BH4-C7; (5.4)
      1BG11-C7; (5.5)-3DH-F5G9 also 5F1F4-T3(5.c)], and the two new monoclonal
      antibodies C14F10Br2 (5.8) and 7F11B5Br3 (5.9), were then tested against
      different meningococcal strains, (63 strains of serogroup A, 60 strains of
      serogroup C (from 1972 to 1974); and 136 strains of serogroup B (from 1992)
      meningococci). Our results demonstrated that the expression of class 5 proteins
      in the N. meningitidis B Brazilian strains studied is highly heterogeneous. The
      serotypes and subtypes of B:4:P1.15, B:4:P1.9, B:4:P1.7, B:4:P1.3, B:4:P1.14,
      B:4:P1.16, B:4:NT, and B:NT:NT were detected in N. meningitidis B serogroups. The
      strains C:2a:P1.2 and A:4.21:P1.9 were dominant in the C and A serogroups,
      respectively. Serogroup B organisms expressed the class 5 epitopes 5.4 (18%), 5.5
      (22%), 5.8 (3.6%), 5.9 (8.0%) and 5c (38%). Serogroup C expressed class 5
      epitopes 5.1 (81%), 5.4 (35%), 5.5 (33%) and 5.9 (5.0%); and serogroup A showed
      reactivity directed at the class 5 protein 5c (47%); and reactivity was present
      with the new monoclonal antibody, 5.9 (5.5%). We conclude that the two new MAbs
      are useful in detecting important group B, class 5 antigens, and that a broad
      selection of serogroup B, class 5 proteins would be required for an effective
      vaccine based on the class 5 proteins.

PMID- 11506779
TI  - Pneumocystis carinii pneumonia, pulmonary tuberculosis and visceral leishmaniasis
      in an adult HIV negative patient.
AB  - This is a case report of a 29 year old male with pneumocystis pneumonia and
      tuberculosis, and who was initially suspected of having HIV infection, based on
      risk factor analyses, but was subsequently shown to be HIV negative. The patient
      arrived at the hospital with fever, cough, weight loss, loss of appetite, pallor,
      and arthralgia. In addition, he was jaundiced and had cervical lymphadenopathy
      and mild heptosplenomegaly. He had interstitial infiltrates of the lung, sputum
      smears positive for Mycobacterium tuberculosis and Pneumocystis carinii, and
      stool tests were positive for Strongyloides stercoralis and Schistosoma mansoni.
      He was diagnosed as having AIDS, and was treated for tuberculosis,
      pneumocystosis, and strongyloidiasis with a good response. The patient did not
      receive anti-retroviral therapy, pending outcome of the HIV tests. A month later,
      he was re-examined and found to have worsening hepatosplenomegaly, pancytopenia,
      fever, and continued weight loss. At this time, it was determined that his HIV
      ELISA antibody tests were negative. A bone marrow aspirate was done and revealed
      amastigotes of leishmania, and a bone marrow culture was positive for Leishmania
      species. He was treated with pentavalent antimony, 20 mg daily for 20 days, with
      complete remission of symptoms and weight gain. This case demonstrates that
      immunosuppression from leishmaniasis and tuberculosis may lead to pneumocystosis,
      and be misdiagnosed as HIV infection. The occurrence of opportunistic infections
      in severely ill patients without HIV must always be considered and alternate
      causes of immunosuppression sought.

PMID- 11506780
TI  - Case reports and qualitative research--two important approaches to evaluation and
      communication in medical science.

PMID- 11506781
TI  - Dynamic and static control of the human knee joint in abduction-adduction.
AB  - It is unclear whether humans can voluntarily control dynamic and static
      properties in knee abduction-adduction, which may be important in performing
      functional tasks and preventing injuries, whether the main load is about the
      abduction axis or not. A joint-driving device was used to perturb the knee in
      abduction-adduction at full knee extension under both passive (muscle relaxed)
      and active (muscle contracted in abduction or adduction) conditions. Dynamic
      control properties in knee abduction-adduction were characterized by joint
      stiffness, viscosity, and limb inertia, and quasi-static knee torque-angle
      relationship was characterized by knee abduction-adduction laxity and quasi
      static stiffness (at a 20Nm moment). It was found that the subjects were capable
      of generating net abduction and adduction moment through differential co
      contraction of muscles crossing the medial and lateral sides of the knee, which
      helped to reduce the abduction-adduction joint laxity (p< or =0.01) and increase
      stiffness (p<0.027) and viscous damping. Knee abduction laxity was significantly
      lower than adduction laxity (p=0.043) and the quasi-static abduction stiffness
      was significantly higher than adduction stiffness (p<0.001). The knee joint
      showed significantly higher stiffness and viscosity in abduction-adduction than
      their counterparts in knee flexion-extension at comparable levels of joint torque
      (p<0.05). Similar to dynamic flexion-extension properties, the system damping
      ratio remained constant over different levels of contraction, indicating
      simplified control tasks for the central nervous system; while the natural
      undamped frequency increased considerably with abduction-adduction muscle
      contraction, presumably making the knee a quicker system during strenuous tasks
      involving strong muscle contraction.

PMID- 11506782
TI  - Response of trunk muscle coactivation to changes in spinal stability.
AB  - The goal of this effort was to assess the neuromuscular response to changes in
      spinal stability. Biomechanical models suggest that antagonistic co-contraction
      may be related to stability constraints during lifting exertions. A two
      dimensional biomechanical model of spinal equilibrium and stability was developed
      to predict trunk muscle co-contraction as a function of lifting height and
      external load. The model predicted antagonistic co-contraction must increase with
      potential energy of the system even when the external moment was maintained at a
      constant value. Predicted trends were compared with measured electromyographic
      (EMG) data recorded during static trunk extension exertions wherein subjects held
      weighted barbells at specific horizontal and vertical locations relative to the
      lumbo-sacral spine junction. The task was designed to assure the applied moment
      was identical during each height condition, thereby changing potential energy
      without influencing moment. Measured EMG activity in the trunk flexors increased
      with height of the external load as predicted by the model. Gender difference in
      spinal stability were also noted. Results empirically demonstrate that the
      neuromuscular system responds to changes in spinal stability and provide insight
      into the recruitment of trunk muscle activity.

PMID- 11506783
TI  - Fetal head moulding: finite element analysis of a fetal skull subjected to
      uterine pressures during the first stage of labour.
AB  - Fetal head moulding is a phenomenon which may contribute to satisfactory progress
      during delivery as it allows the fetal head to accommodate to the geometry of the
      passage. In contrast, excessive head moulding may result in cranial birth
      injuries and thus affect the infant shortly or even long after birth. One group
      of researchers in the past investigated the biomechanics of fetal head moulding
      from an engineering point of view and limited themselves to a static, linear
      model of the parietal bones. In this paper, we present a non-linear model of the
      deformation of a complete fetal skull, when subjected to pressures exerted by the
      cervix, during the first stage of labour. The design of the model involves four
      main steps: shape recovery of the fetal skull, the generation of a valid and
      compatible mesh for finite element analysis (FEA), the specification of a
      physical model and the analysis of deformation. Results of the analysis show good
      agreement with those obtained from clinical experiments on the quantitative
      assessment of fetal head moulding. The model also displays shapes after moulding
      which have been reported in previous studies and which are generally known in the
      obstetric and paediatric communities.

PMID- 11506784
TI  - Circumferential measurement and analysis of strain distribution in the human ACL
      using a photoelastic coating method.
AB  - Large variable deformations of the ligament cannot be adequately quantified by
      one-dimensional and/or localized measurements. To obtain accurate measurement of
      non-uniform strains over the entire surface of anterior cruciate ligament (ACL),
      we used a photoelastic coating technique and a method that allowed us to
      photograph an ACL around its longitudinal axis. A cadaver knee was modified to
      expose its ACL for observation, and the ligament was then coated with a
      photoelastic material. The knee was locked in a jig that allowed simulation of
      natural knee motion. The jig containing the knee was then mounted on a stand,
      which allowed the exposed ACL to be photographed from any angle around its
      longitudinal axis while set at a chosen degree of knee flexion. The jig itself
      was rotated on its stand so as to obtain a panoramic view of the ACL at a given
      knee angle. The obtained images of the photoelastic fringe patterns yielded
      significant information for understanding how the strain distributions along the
      fiber bundles change in association with knee motion. From the results we
      obtained using the photoelastic measuring method, we reached the following
      conclusions. Reciprocal functioning between the anterior and the posterior
      bundles from extension to flexion of the knee does occur. Strain distribution is
      not uniform even along the same bundle. The strain behavior of the ACL under
      uniaxial tensile test does not duplicate the conditions in which the ACL is
      damaged during knee motion. The differences in strains on the ACL under active
      and passive knee motions may not be as large as those reported previously in the
      literature.

PMID- 11506785
TI  - Determination of wave speed and wave separation in the arteries.
AB  - Considering waves in the arteries as infinitesimal wave fronts rather than
      sinusoidal wavetrains, the change in pressure across the wave front, dP, is
      related to the change in velocity, dU, that it induces by the "water hammer"
      equation, dP=+/-rhocdU, where rho is the density of blood and c is the local wave
      speed. When only unidirectional waves are present, this relationship corresponds
      to a straight line when P is plotted against U with slope rhoc. When both forward
      and backward waves are present, the PU-loop is no longer linear. Measurements in
      latex tubes and systemic and pulmonary arteries exhibit a linear range during
      early systole and this provides a way of determining the local wave speed from
      the slope of the linear portion of the loop. Once the wave speed is known, it is
      also possible to separate the measured P and U into their forward and backward
      components. In cases where reflected waves are prominent, this separation of
      waves can help clarify the pattern of waves in the arteries throughout the
      cardiac cycle.

PMID- 11506786
TI  - Application of an anisotropic bone-remodelling model based on a damage-repair
      theory to the analysis of the proximal femur before and after total hip
      replacement.
AB  - In this work, a new model for internal anisotropic bone remodelling is applied to
      the study of the remodelling behaviour of the proximal femur before and after
      total hip replacement (THR). This model considers bone remodelling under the
      scope of a general damage-repair theory following the principles of continuum
      damage mechanics. A "damage-repair" tensor is defined in terms of the apparent
      density and Cowin's "fabric tensor", respectively, associated with porosity and
      directionality of the trabeculae. The different elements of a thermodynamically
      consistent damage theory are established, including resorption and apposition
      criteria, evolution law and rate of remodelling. All of these elements were
      introduced and discussed in detail in a previous paper (Garcia, J. M., Martinez,
      M. A., Doblare, M., 2001. An anisotrophic internal-external bone adaptation model
      based on a combination of CAO and continuum damage mechanics technologies.
      Computer Methods in Biomechanics and Biomedical Engineering 4(4), 355-378.),
      including the definition of the proposed mechanical stimulus and the qualitative
      properties of the model. In this paper, the fundamentals of the proposed model
      are briefly reviewed and the computational aspects of its implementation are
      discussed. This model is then applied to the analysis of the remodelling
      behaviour of the intact femur obtaining densities and mass principal values and
      directions very close to the experimental data. The second application involved
      the proximal femoral extremity after THR and the inclusion of an Exeter
      prosthesis. As a result of the simulation process, some well-known features
      previously detected in medical clinics were recovered, such as the stress
      yielding effect in the proximal part of the implant or the enlargement of the
      cortical layer at the distal part of the implant. With respect to the anisotropic
      properties, bone microstructure and local stiffness are known to tend to align
      with the stress principal directions. This experimental fact is mathematically
      proved in the framework of this remodelling model and clearly shown in the
      results corresponding to the intact femur. After THR the degree of anisotropy
      decreases tending, specifically in the proximal femur, to a more isotropic
      behaviour.

PMID- 11506787
TI  - Comparing predictive validity of four ballistic swing phase models of human
      walking.
AB  - It is unclear to what extent ballistic walking models can be used to
      qualitatively predict the swing phase at comfortable walking speed. Different
      study findings regarding the accuracy of the predictions of the swing phase
      kinematics may have been caused by differences in (1) kinematic input, (2) model
      characteristics (e.g. the number of segments), and (3) evaluation criteria. In
      the present study, the predictive validity of four ballistic swing phase models
      was evaluated and compared, that is, (1) the ballistic walking model as
      originally introduced by Mochon and McMahon, (2) an extended version of this
      model in which heel-off of the stance leg is added, (3) a double pendulum model,
      consisting of a two-segment swing leg with a prescribed hip trajectory, and (4) a
      shank pendulum model consisting of a shank and rigidly attached foot with a
      prescribed knee trajectory. The predictive validity was evaluated by comparing
      the outcome of the model simulations with experimentally derived swing phase
      kinematics of six healthy subjects. In all models, statistically significant
      differences were found between model output and experimental data. All models
      underestimated swing time and step length. In addition, statistically significant
      differences were found between the output of the different models. The present
      study shows that although qualitative similarities exist between the ballistic
      models and normal gait at comfortable walking speed, these models cannot
      adequately predict swing phase kinematics.

PMID- 11506788
TI  - A method to predict muscle control in the kinematically and mechanically
      indeterminate human masticatory system.
AB  - A method is proposed to generate muscle activation patterns for goal-directed
      movements of the human masticatory system. This system is special because apart
      from a larger amount of muscles than degrees of freedom its joints do not
      restrict its movements a priori. Therefore, each muscle is able to influence all
      six degrees of freedom which makes the system kinematically and mechanically
      indeterminate. Furthermore, its working space is principally determined by the
      dynamical properties of its muscles and not by passive constraints. The presented
      method determines the contribution of each degree of freedom to a movement of a
      reference point on the mandible. It avails of straightforward mathematical
      techniques like Linear Programming. It does not require a separate trajectory
      planning step. It was applied in a six degrees of freedom dynamical mathematical
      model of the human masticatory system. This model which was based upon rigid-body
      dynamics incorporating skull morphology and muscle architecture including
      dynamical properties. Movements were exclusively defined by a goal position of
      the mandibular reference point. The method proved to be robust in generating
      muscle activation patterns for both feasible and infeasible movement tasks.
      Generally, they were accomplished faster than habitually observed. If the task
      was infeasible the movement stopped at the outer boundary of the working space at
      the side of the unreachable goal. The method, therefore, enables to explore the
      working space of the mandible and the factors that are relevant for its
      boundaries.

PMID- 11506789
TI  - Dynamic curvature strongly affects wall shear rates in a coronary artery
      bifurcation model.
AB  - This study was motivated by the need for a better understanding of coronary
      artery blood flow patterns and their possible role in atherosclerosis formation.
      Of particular interest in this study was the effects of the dynamic deformation
      due to myocardial contraction on wall shear rate patterns in the coronary
      arteries. A better understanding of these effects on wall shear rate in a
      bifurcation geometry and an evaluation of the importance of these effects was
      desired. A three-dimensional computer model of a bifurcation lying on the surface
      of a sphere with time-varying radius of curvature was employed to simulate the
      motion and deformation of the arteries. The results indicated low mean shear
      rates along the myocardial wall and very high shear rate variations (over 100% of
      the static mean shear rate) along the outer wall. The results obtained using a
      quasi-static analysis were found to underestimate the dynamic wall shear rate
      variation along the myocardial and outer walls. It was concluded that dynamic
      geometry effects are important in determining sites of low mean and oscillating
      wall shear that have been associated with atherogenesis in curved, bifurcating
      arteries.

PMID- 11506790
TI  - Direct perfusion measurements of cancellous bone anisotropic permeability.
AB  - More extensive characterization of trabecular connectivity and intertrabecular
      space will be instrumental in understanding disease states and designing
      engineered bone. This project presents an experimental protocol to define the
      directional dependence of transport properties as measured from healthy
      cancellous bone when considered as a biologic, porous medium. In the initial
      design phases, mature bovine bone was harvested from the femoral neck (n=6
      cylinders) and distal condyle (n=4 cubes) regions and used for "proof of concept"
      experimentation. A power study on those results led to the presented work on 20
      cubic samples (mean volume=4.09cm(3)) harvested from a single bovine distal
      femur. Anisotropic intrinsic permeabilities (k(i)) were quantified along the
      orthogonal anatomic axes (i=medial-lateral, anterior-posterior, and superior
      inferior) from each individual cubic bone sample. Using direct perfusion
      measurements, permeability was calculated based upon Darcy's Law describing flow
      through porous media. The maximum mean value was associated with the superior
      inferior orientation (4.65x10(-10)m(2)) in comparison with the mean anterior
      posterior (4.52x10(-10)m(2)) and medial-lateral (2.33x10(-10)m(2)) direction
      values. The results demonstrate the anisotropic (p=0.0143) and heterogeneous
      (p=0.0002) nature of the tissue and encourage the ongoing quantification of
      parameters within the established poroelastic models.

PMID- 11506791
TI  - Modelling the line of action for the oblique abdominal muscles using an
      elliptical torso model.
AB  - When modelling the line of action of a muscle, anatomical considerations must be
      included if the model is to realistically mimic the muscle behaviour. The
      internal and external oblique muscles are examples of muscles that do not follow
      a straight line between origin and insertion, instead having to wrap around the
      torso. A model is presented which describes the shape of the torso using a right
      elliptical cylinder of varying dimensions. The muscle lines of action are then
      calculated based on this underlying torso shape. The model has been successfully
      fitted to the data reported by Stokes and Gardner-Morse (Journal of Biomechanics
      32(3) (1999) 311). When compared to a linear model, the use of the torso model
      results in a 15% increase in the axial twist moment, and decreases in the lateral
      bend and extension moments (5% and 2%, respectively), able to be generated by the
      internal and external oblique muscles combined in upright stance. These
      differences become larger (up to 37%) when the torso is flexed, extended or
      twisted. The structure of the torso model allows it to be used to model any
      posture without significant increases in the overall model complexity.

PMID- 11506792
TI  - Application of spherical and cylindrical wrapping algorithms in a musculoskeletal
      model of the upper limb.
AB  - In the modelling of the upper limb, many muscles cannot be represented as a
      straight line from origin to insertion due to the complex morphology causing them
      to wrap around passive structures. The majority of bony contours that form these
      obstructions can be described adequately as simple geometric shapes such as
      spheres and cylinders.A novel technique for the parameterisation of muscle paths
      as they wrap around such shapes has been developed for use in an upper limb
      model. The new method involves the definition of moving co-ordinate systems in
      which the path of a wrapped muscle does not move, allowing simplified
      specification. In addition, an analytical calculation of the wrapping path around
      a cylinder is presented over previous approximate methods. Muscle moment arms
      were pre-calculated from vector considerations and within SIMM by tendon
      excursion. Close agreement between the two suggests that the proposed
      implementations accurately follow the theoretical relationship and can be used
      with confidence in musculoskeletal models.

PMID- 11506793
TI  - Spatial reconstruction of the human motion based on images of a single camera.
AB  - The inverse dynamic analysis procedures used in the study of the human gait
      require that the kinematics of the supporting biomechanical model is known
      beforehand. The first step to obtain the kinematic data is the reconstruction of
      human spatial motion, i.e., the evaluation of the anatomic points positions that
      enables to uniquely define the position of all anatomical segments. In
      photogrammetry, the projection of each anatomical point is described by two
      linear equations relating its three spatial coordinates with the two coordinates
      of the projected point. The need for the image of two cameras arises from the
      fact that three equations are necessary to find the original spatial position of
      the anatomical point. It is shown here that the kinematic constraint equations
      associated with a biomechanical model can be used as the extra set of equations
      required for the reconstruction process, instead of the equations associated with
      the second camera. With this methodology, the system of equations arising from
      the point projections and biomechanical model kinematic constraints are solved
      simultaneously. Since the system of equations has multiple solutions for each
      image, a strategy based on the minimization of the cost function associated to
      the smoothness of the reconstructed motion is devised, leading to an automated
      computer procedure enabling a unique reconstruction.

PMID- 11506794
TI  - Antimutagenesis/anticarcinogenesis 2001: mechanistic studies.

PMID- 11506795
TI  - Multiple points of intervention in the prevention of cancer and other mutation
      related diseases.
AB  - Multiple points of intervention are the target for dietary and pharmacological
      interventions aimed at preventing cancer and other diseases in which mutations in
      somatic cells play a pathogenetic role. For instance, our studies showed that DNA
      adducts can be consistently detected in arterial smooth muscle cells from human
      atherosclerotic lesions. Their levels were significantly correlated with the
      occurrence of atherogenic risk factors known from traditional epidemiology and
      were strikingly enhanced in atherosclerotic patients lacking the GSTM1 genotype.
      Cancer chemoprevention has a dual goal, i.e. prevention of occurrence of the
      disease (primary prevention) and early detection and reversion of tumors at a
      premalignant stage (secondary prevention). At a later stage, attempts can be made
      to prevent local recurrences as well as invasion and metastasis of malignant
      cells (tertiary prevention). For a rational use of chemopreventive agents it is
      essential not only to evaluate their efficacy and safety but also to understand
      the mechanisms involved. Sometimes it is difficult to discriminate whether
      modulation of a given end-point is actually a specific mechanism or rather the
      epiphenomenon of other events. For instance, we recently found that apoptosis is
      considerably stimulated in the respiratory tract of smoke-exposed rats; whereas
      certain chemopreventive agents work by further enhancing smoke-related apoptosis,
      other agents appear to downregulate apoptosis simply because they inhibit the
      genotoxic events signaling this process. We propose here a detailed, updated
      classification of the points of intervention exploitable in the prevention of
      mutation and cancer. The general outline includes a variety of extracellular and
      cellular mechanisms modulating the genotoxic response and tumor initiation as
      well as tumor promotion, progression, angiogenesis, invasion, and metastasis.
      This classification is not intended to provide a rigid scheme, since several
      intervention points are reiterated several times over different phases of the
      process. Moreover, some mechanisms are strictly interconnected or partially
      overlapping. Interestingly, a number of chemopreventive agents work through
      multiple mechanisms, which warrants a higher efficacy and a broader spectrum of
      action. It is also convenient to combine chemopreventive agents working through
      complementary mechanisms. In recent preclinical studies, we observed that
      combination of N-acetylcysteine with either oltipraz or ascorbic acid produces
      additive or more than additive protective effects towards early biomarkers and/or
      experimentally-induced tumors.

PMID- 11506796
TI  - Antimutagenesis and anticarcinogenesis, from the past to the future.
AB  - Observations on cancer causation are some 150 years old, but actual detailed
      research on elements bearing on cancer started at the beginning of the twentieth
      century. Rapid progress, however, is only some 40 years old. Studies in humans
      documented certain lifestyle related factors to lead to cancer, and research in
      animal models strengthened this information. With the realization that there are
      carcinogens that in a metabolically activated attack DNA, in contrast to other
      agents that act by promoting, enhancing processes through totally distinct
      mechanisms, it became possible to develop and apply tests for DNA reactivity, in
      a prokaryotic organism, the widely used Salmonella typhimurium test by Ames and
      in a eukaryotic system, namely freshly explanted liver cells displaying evidence
      of DNA repair by Williams. A battery of these two tests are over 90% accurate in
      defining genotoxicity. Virtually all documented human carcinogens are genotoxic.
      With advances in molecular biology, mutational events are traced to changes in
      tumor suppressor genes or in oncogenes, that can serve as markers of risk. In
      addition, reactive oxygen systems (ROS) are involved in both the early steps in
      cancer and in the developmental aspects. Thus, foods containing antioxidants such
      as vegetables, fruits, soy products, cocoa and tea that counteract ROS are
      protective in cancer causation and development. Worldwide application of current
      knowledge and mechanisms to cancer prevention, the definitive means of cancer
      control, is likely to lower not only cancer but also heart disease risk in the
      current century.

PMID- 11506797
TI  - Genomic integrity and the repair of double-strand DNA breaks.
AB  - The induction of double-strand breaks (DSBs) in DNA by exposure to DNA damaging
      agents or as intermediates in normal cellular processes, creates a severe threat
      for the integrity of the genome. Unrepaired or incorrectly repaired DSBs lead to
      broken chromosomes and/or gross chromosomal rearrangements which are frequently
      associated with tumor formation in mammals. To maintain the integrity of the
      genome and to prevent the formation of chromosomal aberrations, several pathways
      exist in eukaryotes: homologous recombination (HR), non-homologous end joining
      (NHEJ) and single-strand annealing (SSA). These mechanisms are conserved in
      evolution, but the relative contribution depends on the organism, cell type and
      stage of the cell cycle. In yeast, DSBs are primarily repaired via HR while in
      higher eukaryotes, both HR and NHEJ are important. In mammals, defects in both HR
      or NHEJ lead to a predisposition to cancer and at the cellular level, the
      frequency of chromosomal aberrations is increased. This review summarizes our
      current knowledge about DSB-repair with emphasis on recent progress in
      understanding the precise biochemical activities of individual proteins involved.

PMID- 11506798
TI  - Recommended dietary allowances (RDAs) for genomic stability.
AB  - Diet as a key factor in determining genomic stability is more important than
      previously imagined because we now know it impacts on all relevant pathways, i.e.
      exposure to dietary carcinogens, activation/detoxification of carcinogens, DNA
      repair, DNA synthesis and apoptosis. Current recommended dietary allowances for
      vitamins and minerals are based largely on the prevention of diseases of
      deficiency such as scurvy in the case of Vitamin C. Because diseases of
      development, degenerative disease and ageing itself are partly caused by damage
      to DNA, it seems logical that we should focus better our attention on defining
      optimal requirements of key minerals and vitamins for preventing damage to both
      nuclear and mitochondrial DNA. To date our knowledge on optimal micronutrient
      levels for genomic stability is scanty and disorganised. Appropriately designed
      placebo, controlled trials are required to define recommended dietary allowances
      for genomic stability. Recently, it has been shown that above RDA intakes of
      folic acid and Vitamin B12 are required to reduce the micronucleus index in
      humans by 25%. In the future, clinical trials with a defined wider array of
      complementary DNA damage end-points would be necessary. That there is a need for
      an international collaborative group to establish RDAs for genomic stability is
      self-evident and this paper is a call for such a process to begin.

PMID- 11506799
TI  - The antimutagenic effect of vanillin and cinnamaldehyde on spontaneous mutation
      in Salmonella TA104 is due to a reduction in mutations at GC but not AT sites.
AB  - Vanillin (VAN) and cinnamaldehyde (CIN) are dietary antimutagens that, when added
      to assay plates, reduced the spontaneous mutant frequency in Salmonella
      typhimurium strain TA104 (hisG428, rfa, uvrB, pKM101) by 50%. To date, no study
      has demonstrated whether or not the antimutagenic effects of an agent are due to
      a reduction in all classes of mutations or to a reduction in selective classes of
      mutations. To explore this issue, we have determined the spontaneous mutation
      spectrum in TA104 as well as the mutation spectrum after treatment of cells with
      antimutagens at concentrations that produced approximately a 50% reduction in
      mutant frequency but only a 10% reduction in survival. Statistical analysis
      revealed no significant difference between the mutation spectra of VAN- and CIN
      treated cells. Relative to untreated cells, treatment with either VAN or CIN
      produced a significant reduction in mutations at GC sites, whereas neither
      compound produced a significant reduction in mutations at AT sites.
      Antimutagenesis experiments in hisG428 strains of Salmonella with varying DNA
      repair backgrounds showed that VAN and CIN require SOS repair genes to produce an
      antimutagenic effect against spontaneous mutagenesis. Studies evaluating the
      effect of VAN and CIN on growth rate showed that neither compound suppressed
      growth relative to untreated cells. To our knowledge, this is the first study to
      examine if an antimutagen reduced all or just some classes of mutations that were
      available for reduction.

PMID- 11506800
TI  - The antimutator phenotype of E. coli mud is only apparent and results from
      delayed appearance of mutants.
AB  - Antimutator strains are strains that have a lower mutation rate than the wild
      type strain. We have reexamined the properties of one reported antimutator strain
      of Escherichia coli, termed mud [Mol. Gen. Genet. 153 (1977) 87]. This strain
      contains a temperature-sensitive mutation in the purB gene, leading to adenine
      dependent growth at higher temperature. When grown at permissive or semi
      permissive temperature in the absence of adenine it displays large reductions in
      the number of both spontaneous and mutagen-induced mutants (e.g. several hundred
      fold for valine-resistant mutants). However, our studies show that strains
      containing the purB allele generate mutations at the same level as the wild-type
      strain, and that the apparent antimutator effect is the consequence of the
      delayed appearance of mutants on the selective plates. This delay likely results
      from the combined stress exerted by the adenine deficiency and the presence of
      the selective agent (i.e. valine).

PMID- 11506801
TI  - Contribution of E. coli AlkA, TagA glycosylases and UvrABC-excinuclease in MMS
      mutagenesis.
AB  - MMS, an S(N)2 alkylating agent, is a moderate inducer of SOS mutagenesis and
      adaptive response. Our previous studies have shown that transient starvation of
      Escherichia coli AB1157argE3 strain causes a decrease of MMS-induced argE3-
      >Arg(+) reversions and this decrease is accompanied by the disappearance of the
      Fpg protein sensitive sites on plasmids isolated from MMS-treated and
      subsequently starved bacteria. This suggests that in such cells the mutation
      frequency decline (MFD) repair takes place. Here, we study the relation between
      MMS-induced mutagenesis as well as mutation frequency decline during starvation,
      and the repair of alkylated bases and AP-sites by base and nucleotide excision
      repair systems. In the AB1157alkA(-) strain, MMS-induced mutagenesis was over
      five-fold higher than in the wild type strain and no MFD repair occurred during
      starvation. Surprisingly, the lack of TagA glycosylase diminished MMS mutagenesis
      and accelerated the MFD effect. However, in double tagA(-)alkA(-) mutant, the
      frequency of Arg(+) reversions increased over 10-fold during 60 min of aminoacid
      starvation after MMS-treatment. Lack of the uvrA gene function did not affect the
      MMS-induced mutation rate and MFD in AB1157alkA(+)tagA(+). Starvation of MMS
      treated AB1157tagAalkAuvrA triple mutant caused a decrease of mutation frequency
      almost to the level of spontaneous mutation rate. Examination of the repair of 3
      MeAde, 7-MeGua and AP sites during starvation using repair glycosylases and
      plasmids isolated from MMS-treated and starved bacteria revealed that in E. coli
      uvr(+) but tagAalkA strain, neither 3-MeAde nor 7-MeGua were repaired during 60
      min starvation and these persistent lesions could be responsible for the
      induction of the SOS system and an increase in mutation rate during starvation.
      In the triple tagAalkAuvrA mutant the repair of 3-MeAde, 7-MeGua and AP sites was
      carried out effectively and this could explain the observed decrease in the
      mutation rate during starvation. These results suggest that only in the absence
      of the "first choice" repair enzymes TagA, AlkA glycosylases and UvrABC
      excinuclease, a third error-free repair system of alkylated bases is activated.
      In the absence of only TagA and AlkA glycosylases, UvrABC excinuclease mediates
      activation of the SOS response, and this results in an increase of mutagenesis
      induced by the presence of alkylated bases in DNA.

PMID- 11506802
TI  - Reduction of spontaneous mutagenesis in mismatch repair-deficient and proficient
      cells by dietary antioxidants.
AB  - Cells lacking mismatch repair (MMR) exhibit elevated levels of spontaneous
      mutagenesis. Evidence exists that MMR is involved in repair of some DNA lesions
      besides mismatches. If some oxidative DNA lesions are substrates for MMR, then
      the excess mutagenesis in MMR(-) cells might be blocked by dietary antioxidants.
      Effects of the dietary antioxidants ascorbate, alpha-tocopherol, (-)
      epigallocatechin gallate (EGCG) and lycopene on spontaneous mutagenesis were
      studied using mismatch repair-deficient (hMLH1(-)) human colon carcinoma HCT116
      cells and HCT116/ch3 cells, in which normal human chromosome 3 has been added to
      restore mismatch repair. HCT116 cells have a 22-fold higher spontaneous mutation
      rate compared with HCT116/ch3 cells. HCT116 cells cultured in 1% fetal bovine
      serum (FBS) have twice the spontaneous mutation rate of those cultured in 10%
      FBS, most likely due to reduction in serum antioxidants in the low serum medium.
      As expected, alpha-tocopherol (50 microM) and ascorbate (284 microM) reduced
      spontaneous mutagenesis in HCT116 cells growing in 1% serum more dramatically
      than in cells cultured in 10% serum. The strongest antimutagenic compound was
      lycopene (5 microM), which reduced spontaneous mutagenesis equally (about 70%) in
      HCT116 cells growing in 10 and 1% FBS and in HCT116/ch3 cells. Since lycopene was
      equally antimutagenic in cells growing in low and high serum, it may have another
      antimutagenic mechanism in addition to its antioxidant effect. Surprisingly, EGCG
      (10 microM) was toxic to cells growing in low serum. It also reduced spontaneous
      mutagenesis equally (nearly 40%) in HCT116 and HCT116/ch3 cells. The large
      proportion of spontaneous mutagenesis that can be blocked by antioxidants in
      mismatch repair-deficient cells support the hypothesis that a major cause of
      their excess mutagenesis is endogenous oxidants. Blocking spontaneous
      mutagenesis, perhaps with a cocktail of antioxidants, should reduce the risk of
      cancer in people with a genetic defect in mismatch repair as well as other
      individuals.

PMID- 11506803
TI  - Effect of chemopreventive agents on DNA adduction induced by the potent mammary
      carcinogen dibenzo[a,l]pyrene in the human breast cells MCF-7.
AB  - Over 1500 structurally diverse chemicals have been identified which have
      potential cancer chemopreventive properties. The efficacy and mechanisms of this
      growing list of chemoprotective agents may be studied using short-term bioassays
      that employ relevant end-points of the carcinogenic process. In this study, we
      have examined the effects of eight potential chemopreventive agents, N
      acetylcysteine (NAC), benzylisocyanate (BIC), chlorophyllin, curcumin, 1,2
      dithiole-3-thione (D3T), ellagic acid, genistein, and oltipraz, on DNA adduction
      of the potent mammary carcinogen dibenzo[a,l]pyrene (DBP) using the human breast
      cell line MCF-7. Bioactivation of DBP by MCF-7 cells resulted in the formation of
      one predominant (55%) dA-derived and several other dA- or dG-derived DNA adducts.
      Three test agents, oltipraz, D3T, and chlorophyllin substantially (>65%)
      inhibited DBP-DNA adduction at the highest dose tested (30 microM). These agents
      also significantly inhibited DBP adduct levels at a lower dose of 15 microM,
      while oltipraz was effective even at the lowest dose of 5 microM. Two other
      agents, genistein and ellagic acid were moderate (45%) DBP-DNA adduct inhibitors
      at the highest dose tested, while NAC, curcumin, and BIC were ineffective. These
      studies indicate that the MCF-7 cell line is an applicable model to study the
      efficacy of cancer chemopreventive agents in a human setting. Moreover, this
      model may also provide information regarding the effect of the test agents on
      carcinogen bioactivation and detoxification enzymes.

PMID- 11506804
TI  - Isolating antigenotoxic components and cancer cell growth suppressors from
      agricultural by-products.
AB  - Commercial processing wastes or by-products of crops were found to be sources of
      antimutagens and human tumor cell growth suppressors. We developed a microplate
      method to measure genomic DNA damage in Chinese hamster ovary cells with a
      modified single cell gel electrophoresis (SCGE) assay. This allowed us to measure
      the repression of 2-acetoxyacetylaminofluorene (2AAAF)-induced DNA damage by very
      small amounts of complex mixtures, fractions or individual chemicals isolated
      from agricultural by-products. We previously demonstrated that PCC, an ethanol
      extract of a commercial soybean processing by-product, repressed induced genomic
      DNA damage in mammalian cells. PCC was separated into a series of chemically
      defined fractions and two fractions (PCC70 and PCC100) repressed mutagen-induced
      damage. Of the isoflavones isolated from soybean fraction PCC70, daidzein
      expressed antigenotoxic activity, however, genistin and genistein enhanced DNA
      damage. An antigenotoxic response also was observed with a fraction isolated from
      corn distillate solids (CDS40). We developed a microplate assay to measure the
      suppression of the growth rate of human cancer cells in which the
      cytostatic/cytotoxic status at each concentration of the test sample was
      quantitatively determined. Genistein, genistin, daidzein and daidzin isolated
      from soybean fraction PCC70 expressed a wide range of growth suppression of HT-29
      human colon cancer cells. The biological assays were integrated with, and
      directed, the separation and analytical chemistry component of this project.
      Compounds were purified from biologically active fractions and the structure of
      individual chemicals was determined with analytical HPLC and LC-mass spectroscopy
      (LC-MS). This research may lead to the isolation of novel chemoprotectants from
      agronomic commercial processing products and by-products.

PMID- 11506805
TI  - Soy isoflavonoids and cancer -- metabolism at the target site.
AB  - Isoflavonoids are members of the broad class of plant polyphenols that have been
      shown in vivo to have benefit in the prevention of a wide variety of chronic
      diseases, including cancer. For genistein (5,7,4'-trihydroxyisoflavone) (GEN),
      the major isoflavone in soy, reported mechanisms for these biological activities
      are numerous and include regulation of estrogen-mediated events, inhibition of
      tyrosine kinase and DNA topoisomerase activities, synthesis and release of TGF
      beta, and modulation of apoptosis. However, the biochemical effects of GEN in
      cell culture occur at concentrations in the micromolar range, far above the
      circulating levels of the unconjugated GEN. This may point to the limitations of
      cell culture for the evaluation of the activity and mechanisms of potential anti
      carcinogens. GEN is extensively metabolized in vivo, with only about 14-16%
      excreted in an unmodified form. Metabolism may also occur because of interaction
      between GEN (as well as other polyphenols) and oxidants produced by inflammatory
      cells (HOCl, HOBr and ONOO(-)). These react with GEN to form brominated,
      chlorinated and/or nitrated GEN. Emerging evidence indicates that these
      modifications may substantially increase the biological activities of the parent
      compound. Future investigations of GEN and other polyphenols must, therefore,
      take into account metabolism at the tissue site.

PMID- 11506806
TI  - Impact of bacteria in dairy products and of the intestinal microflora on the
      genotoxic and carcinogenic effects of heterocyclic aromatic amines.
AB  - This article gives a short overview on the present state of knowledge of the
      effects of the intestinal microflora on the health hazards of heterocyclic
      aromatic amines (HAs). Results of single cell gel electrophoresis assays with
      conventional, germ free and human flora associated rats indicate that the
      presence of intestinal microorganisms strongly enhances the induction of DNA
      damage in colon and liver cells by IQ. Furthermore, it was found that
      supplementation of the feed with Lactobacilli attenuates the induction of colon
      cancer by this same amine. These recent findings suggest that the intestinal
      microflora and lactic acid bacilli in dairy products strongly affect the health
      risks of HAs. Nevertheless, most previous experiments with HAs focused on the
      involvement of mammalian enzymes in the biotransformation of these compounds and
      only a few articles are available which concern interactions of bacteria with
      HAs. Some of these studies suggested that the formation of directly mutagenic
      hydroxy-metabolites of the amines by fecal bacteria might be an important
      activation pathway but it turned out that the hydroxy-derivative of IQ is not
      genotoxic in mammalian cells and does not cause colon cancer in laboratory
      rodents. There is some evidence that hydrolysis of HA-metabolites by bacterial ss
      glucuronidase might play a role in the activation of HAs but experimental data
      are scarce and no firm conclusions can be drawn at present. The most important
      detoxification mechanism appears to be the direct binding of the HAs to the cell
      walls of certain bacterial strains contained in fermented foods. It was shown
      that these effects do also take place under physiologically relevant conditions.
      Overall, it seems that intestinal bacteria play a key role in the activation and
      detoxification of HAs which has been an area of research long ignored. The
      elucidation of these mechanisms may enable the development of biomarkers for
      colon cancer risk and nutritional strategies of protection.

PMID- 11506807
TI  - Preventive effects of anthraquinone food pigments on the DNA damage induced by
      carcinogens in Drosophila.
AB  - We have previously demonstrated the inhibitory effect of chlorophyllin, a green
      food additive, on the genotoxicities of various carcinogens in Drosophila.
      Recently, we reported that purpurin, a component of a red food additive produced
      from madder root (Rubia tinctorium), inhibits the bacterial mutagenicity of
      heterocyclic amines. In the present study, we examined antigenotoxic activities
      of various pigments that are either constituents of food or food additives, using
      Drosophila in vivo DNA repair assay. Third instar larvae of Drosophila were fed a
      mutagen with or without pigment. The resulting adult flies were monitored for
      their male (repair deficient)/female (repair proficient) ratios, which reflect
      the DNA damage. We tested a total of 20 pigments, which are mainly of plant
      origins, including flavonoids, carotenoids, anthocyanins, anthraquinones and beta
      diketone (curcumin)-derivatives, against the genotoxicities of eight carcinogens;
      IQ, MeIQx, AFB1, NDMA, 2-AAF, DMBA, 4NQO, and MNU. Four anthraquinone pigments
      (alizarin, purpurin, lac color, and cochineal extract) showed significant
      antigenotoxic activities. Alizarin and purpurin suppressed the DNA damage induced
      by IQ, MeIQx, AFB1, NDMA, 2-AAF, DMBA, and MNU. Lac color and cochineal extract
      showed inhibition against IQ, MeIQx, AFB1, 2-AAF and DMBA. In these inhibitions,
      suppression of metabolic enzymes may be involved. Since purpurin and alizarin
      suppressed the activity of MNU, a direct alkylating agent, there may also be a
      mechanism distinct from enzyme inhibitions in these anthraquinone-mediated
      suppressions of DNA damage.

PMID- 11506808
TI  - Protective effect of green tea against benzo[a]pyrene-induced mutations in the
      liver of Big Blue transgenic mice.
AB  - We assessed the ability of green tea to protect against benzo[a]pyrene (B[a]P)
      induced mutations in the liver of lacI transgenic male C57BL/6 Big Blue mice. The
      mice were given a 2% Japanese green tea hot water extract as their sole source of
      drinking water for 10 weeks. After 7 weeks, they received a total dose of 150
      mg/kg B[a]P. Treatment with B[a]P resulted in a two-fold higher lacI mutant
      frequency than the untreated controls (8.6+/-0.8 x 10(-5) versus 4.0+/-0.7 x 10(
      5), P=0.01). B[a]P increased the frequency of its characteristic mutation (GC-
      >TA transversions) nearly five-fold, from 0.75 x 10(-5) to 3.7 x 10(-5). In mice
      treated with green tea, the induced B[a]P mutant frequency decreased by 63%,
      while GC-->TA transversions were reduced by 54%. Thus, we report evidence that
      green tea extract significantly suppressed B[a]P-induced mutation by lowering its
      specific transversion mutation in the lacI transgene in vivo. Further studies
      will address the correlation between the modulation of metabolic enzymes and the
      protection against induced mutation by green tea.

PMID- 11506809
TI  - Reduction in DNA damage in brain and peripheral blood lymphocytes of elderly dogs
      after treatment with dehydroepiandrosterone (DHEA).
AB  - Steady state levels of DNA damage are substantial in vertebrate animals as a
      consequence of exposure to endogenous and environmental mutagens. DNA damage may
      contribute to organismal senescence and an increased risk for specific age
      related diseases. In this study, we determined if treatment with the neuroactive
      adrenal steroid, dehydroepiandrosterone (DHEA), which exhibits antioxidant and
      anticarcinogenic properties in rodents, would reduce DNA damage in the brain and
      peripheral blood lymphocytes (PBLs) of elderly dogs. Elderly male dogs,
      physiologically equivalent to 59-69-year-old men, were randomly assigned to
      receive no treatment (n=9 dogs) or DHEA at 100mg/kg PO daily (n=8 dogs). Extent
      of DNA damage in brain cells and PBLs was measured using alkaline comet assay.
      The effect of DHEA treatment on the susceptibility of PBLs to H(2)O(2)-induced
      DNA damage was also measured. We found that elderly male dogs receiving daily
      DHEA treatment for 7 months had significantly less DNA damage detectable in their
      brain compared to age-matched control dogs. After 7 months treatment, DHEA
      treated dogs also had a significant reduction in DNA damage in PBLs compared to
      pre-treatment levels. We also found that PBLs of dogs treated with DHEA were more
      resistant to H(2)O(2)-induced DNA damage than PBLs of untreated dogs. Our results
      did not show that basal DNA damage in PBLs was strongly correlated with DNA
      damage within the brain. The results of this study suggest that DHEA
      supplementation can significantly reduce steady state levels of DNA damage in the
      mammalian brain. Further evaluation of DHEA as a neuroactive agent and its
      effects on DNA damage and gene expression in other tissues and species is
      warranted.

PMID- 11506810
TI  - Influence of dietary antioxidants on the mutagenicity of 7,12
      dimethylbenz[a]anthracene and bleomycin in female rats.
AB  - Studies on agents that modulate carcinogen-induced genotoxic effects in
      experimental animals provide end points that can be used for assessing the
      antimutagenic or anticarcinogenic properties of putative chemopreventive
      compounds and for predicting their protective efficacy in humans. In this study,
      we investigated the ability of the dietary antioxidant Vitamins C, E, beta
      carotene and the mineral selenium to inhibit the mutant frequency (MF) induced by
      treatment of rats with 7,12-dimethylbenz[a]anthracene (DMBA), a mammary
      carcinogen and bleomycin (BLM), an anti-tumor agent that can damage DNA by free
      radical mechanisms. Both chemicals have been previously shown to be mutagenic in
      the rat lymphocyte Hprt assay. Adult female Fischer 344 rats were given the
      antioxidants singly or in a combination 2 weeks prior to mutagen treatment.
      Antioxidant intake continued for an additional 4 weeks post-mutagen treatment. At
      sacrifice, spleens were aseptically removed for the isolation of lymphocytes to
      conduct the mutagenesis assay at the Hprt locus. The DMBA and BLM treatment
      induced a marked increase in MF, 52.8 x 10(-6) and 19.2 x 10(-6), respectively,
      over the controls. The MFs seen in the individual antioxidants alone (single or
      mixture) were relatively similar to the controls, with the exception of Vitamins
      C and E, that had 1.7- and 1.5-fold increase, respectively. The degree of
      inhibitory response was dependent on the type of mutagen and the particular
      antioxidant. BLM/antioxidant combination had inhibitions ranging from 44 to 80%,
      while DMBA/antioxidant system ranged from 60 to 93%, with Vitamins C and E
      achieving the highest inhibition in both systems. The mixture displayed low
      inhibitory responses, 44.6% for BLM/mix and 47% DMBA/mix. On the whole, the
      results indicate that the dietary constituents tested are antimutagenic; however,
      because of the gradations seen with the responses, the protective efficacy of
      these antioxidants may depend on the type of mutagen/carcinogen they encounter.
      Pending molecular analysis of mitochondrial DNA mutations will also indicate
      whether there is a shift in the mutational spectra produced by the carcinogens in
      the presence of antioxidants.

PMID- 11506811
TI  - Inhibitory effect of naringin on the micronuclei induced by ifosfamide in mouse,
      and evaluation of its modulatory effect on the Cyp3a subfamily.
AB  - Naringin (Nar) is a flavonone found in high amount in grapefruit. In in vitro
      studies to determine its antimutagenicity results have been both positive and
      negative. On the other hand, an increase in the bioavailability of some
      medicaments have been observed when these are ingested together with grapefruit.
      It has been suggested that the effect may be related to the inhibition of the
      human enzyme Cytochrome P450 (CYP) 3A4 by Nar, an enzyme with a high aminoacid
      sequence homology with the Cyp3a in mouse. The present study was designed for
      three main purposes: (1) to determine whether Nar has a genotoxic effect in mouse
      in vivo. This was evaluated by measuring the rate of micronucleated polychromatic
      erythrocytes (MNPE); (2) to determine its antigenotoxic and its anticytotoxic
      potential on the damage produced by ifosfamide (Ifos). The first study was done
      by scoring the rate of MNPE, and the second one by establishing the index
      polychromatic erythrocytes/normochromatic erythrocytes (PE/NE); and (3) to
      explore whether its antigenotoxic mechanism of action is related to an inhibitory
      effect of Nar on the expression of the Cyp3a enzyme, an effect which could avoid
      the biotransformation of Ifos. A single oral administration was used for all
      groups in the experiment: three groups were given different doses of Nar (50,
      250, and 500 mg/kg), other groups received the same doses of Nar plus an
      administration of Ifos (60 mg/kg), another group treated with distilled water and
      another with Ifos (60 mg/kg) were used as negative and positive controls,
      respectively. The micronuclei and the cell scoring were made in blood samples
      taken from the tail of the animals at 0, 24, 48, 72, and 96 h. The results showed
      that Nar was neither genotoxic nor cytotoxic with the doses tested, but Ifos
      produced an increase in the rate of MNPE at 24 and 48 h. The highest value was
      24+/-1.57 MNPE per thousand cells at 48 h. The index PE/NE was significantly
      reduced by Ifos at 24 and 48 h. Concerning the antigenotoxic capacity of Nar, a
      significant decrease was observed in the MNPE produced by Ifos at the three
      tested doses. This effect was dose-dependent, showing the highest reduction in
      MNPE frequency (54.2%) at 48 h with 500 mg/kg of Nar. However, no protection on
      the cytotoxicity produced by Ifos was observed. Immunoblot analysis was used to
      assess the Cyp3a expression in liver and intestinal microsomes from mouse exposed
      orally to Nar. An induction in the Cyp3a protein was observed in both intestinal
      and hepatic microsomes from treated mice. This induction correlated with an
      increase in erythromycin N-demethylase activity. These data suggest that other
      mechanism(s) are involved in the antigenotoxic action of naringin.

PMID- 11506812
TI  - Inhibition of benzo[a]pyrene- and cyclophoshamide-induced mutagenicity by
      Cinnamomum cassia.
AB  - Cinnamomum cassia is used as a flavoring spice with some established medicinal
      properties. In this study, we evaluated the antimutagenic effect of C. cassia
      against two mutagens, viz. benzo[a]pyrene (B[a]P) and cyclophosphamide (CP). The
      antimutagenic properties of C. cassia were examined by the Ames test. In vivo
      chromosomal aberration (CA) and micronuclei tests were also employed to assess
      the antimutagenic effect of C. cassia in mice after pretreatment with the extract
      orally for seven consecutive days. To elucidate the mechanism by which C. cassia
      exerts its antimutagenic effect, certain key enzymes involved in bioactivation
      and detoxification processes were also investigated. Changes in liver cytochrome
      P450 (Cyt P450), glutathione content (GSH), glutathione S-transferase (GST),
      glutathione reductase (GR), and glutathione peroxidase (GPX) were evaluated in
      pretreated animals. It was observed in the Ames test, bone marrow chromosomal
      aberration assay, and micronucleus test that C. cassia exerted significant
      antimutagenic effects against B[a]P and CP in animals treated with the plant
      extract. C. cassia pretreatment decreased Cyt P450 content but increased GSH
      content and the activity of glutathione-dependent antioxidant enzymes, viz. GST,
      GR, and GPX. The present findings demonstrate that the antimutagenic potential of
      C. cassia could be attributed to its modulatory effect on the xenobiotic
      bioactivation and detoxification processes.

PMID- 11506813
TI  - Involvement of oxidative stress in experimentally induced reflux esophagitis and
      Barrett's esophagus: clue for the chemoprevention of esophageal carcinoma by
      antioxidants.
AB  - Oxidative damage has long been related to mucosal damages of gastrointestinal
      tracts and their ensuing carcinogenesis. In spite of treatment with anti
      secretory medications for reflux esophagitis, considerable portions of patient
      did not achieve the complete mucosal healings or suffered from sustaining
      symptoms or development of dread complication like Barrett's esophagus,
      suggesting other damaging factors or impaired mucosal resistance are also
      involved in their pathogenesis. The present study was designed either to evaluate
      the oxidative stress as the major pathogenic factor of reflux esophagitis or to
      find out the usefulness of antioxidant in the treatment of reflux esophagitis and
      the prevention of development of Barrett's esophagus. Acute or chronic reflux
      esophagitis was induced through either narrowing the third portion of duodenal
      lumen or performing myotomy of lower esophageal sphincter in rats, respectively.
      DA-9601, a new phytopharmaceutical possessing antioxidative properties,
      significantly attenuated the gross and histopathologic scores of acute reflux
      esophagitis in a dose-dependent manner compared to those treated with ranitidine
      alone. Only scattered erosions were observed in antioxidant pre-treated group,
      but acid suppression by ranitidine was not so effective in decreasing the
      severity of reflux esophagitis. Significantly increased amounts of
      malondialdehyde (MDA), increased NF-kappa B activations, and depletions of
      reduced glutathione (GSH) were observed in experimentally induced reflux
      esophagitis, but DA-9601 pre-treatment attenuated the decrement of mucosal GSH
      levels and decreased MDA formations significantly. DA-9601 treatment showed
      significant reductions in the activation of NF-kappa B transcription factor. DA
      9601 significantly decreased the proliferating cell nuclear antigen-labeling
      index (PCNA-LI) of esophagus (P<0.05) in chronic reflux esophagitis model and
      prevented the development of Barrett's esophagus. In conclusion, reflux
      esophagitis provoked considerable levels of oxidative stress in the esophageal
      mucosa. Antioxidant treatment seems to be the first line therapeutics in the
      prevention or treatment of reflux esophagitis. Moreover, antioxidant possibly
      played the chemopreventive role through preventing the development of Barrett's
      esophagus.

PMID- 11506814
TI  - Cell proliferation in cancer prevention; effects of preventive agents on estrogen
      related endometrial carcinogenesis model and on an in vitro model in human
      colorectal cells.
AB  - Proto-oncogenes such as c-fos, c-jun and c-myc are known to relate to cell
      proliferation and differentiation. Some oriental herbal medicines like
      Glycyrrhizae radix or Juzen-taiho-to were found to suppress estradiol-17 beta
      (E2)-induced expression of c-fos/jun in uterine corpus and inhibited N-methyl-N
      nitrosourea and E2-induced endometrial carcinogenesis in mice. It is suggested
      that the effects of such oriental drugs are exerted probably through suppression
      of estrogen-induced c-fos/jun expression and they are promising preventing agents
      for endometrial cancers. In the combined in vitro assay for cell proliferation
      (MTS assay) and apoptosis (DNA fragmentation) in human colorectal cancer cells
      (Colo 320), a number of naturally occurring chemopreventive agents such as
      curcumin, quercetin, auraptene, 1'-acetoxychavicol acetate (ACA) and indole-3
      carbinol were shown to generate apoptosis as well as to inhibit cell
      proliferation. The results suggest a mode of action of these chemopreventive
      agents and also imply that such in vitro short term assay is useful for detection
      of new agents for cancer prevention.

PMID- 11506815
TI  - The role of alpha 6 beta 1 integrin and EGF in normal and malignant acinar
      morphogenesis of human prostatic epithelial cells.
AB  - Complex multiple interactions between cells and extracellular matrix occur during
      acinar morphogenesis involving integrin receptors and growth factors. Changes in
      these interactions occur during carcinogenesis as cells progress from a normal to
      a malignant, invasive phenotype. We have developed human prostatic epithelial
      cell lines of the same lineage, which represent multiple steps in carcinogenesis,
      similar to prostatic intraepithelial neoplasia and subsequent tumor progression.
      The non-tumorigenic, RWPE-1 and the tumorigenic WPE1-NB27 and WPE1-NB26 cell
      lines were used to examine their ability to undergo acinar morphogenesis in a 3-D
      cell culture model and its relationship to invasion, integrin expression and EGF
      presence. An inverse relationship between the degree of acinar formation and
      invasive ability was observed. The non-tumorigenic, non-invasive RWPE-1 and the
      low tumorigenic, low invasive, WPE1-NB27 cells show high and decreased acinar
      forming ability, respectively, while the more invasive WPE1-NB26 cells show a
      loss of acinar formation. While RWPE-1 acini show basal expression of alpha 6
      beta 1 integrin, which correlates with their ability to polarize and form acini,
      WPE1-NB27 cells lack alpha 6 but show basal, but weaker expression of beta 1
      integrin. WPE1-NB26 cells show loss alpha 6 and abnormal, diffused beta 1
      integrin expression. A dose-dependent decrease in acinar formation was observed
      in RWPE-1 cells when cell proliferation was induced by EGF. Anti-functional
      antibody to EGF caused an increase in acinar formation in RWPE-1 cells. These
      results suggest that malignant cells lose the ability to undergo acinar
      morphogenesis and that the degree of this loss appears to be related to invasive
      ability, EGF levels and alterations in laminin-specific integrin expression. This
      model system mimics different steps in prostate carcinogenesis and has
      applications in the secondary and tertiary prevention of prostate cancer.

PMID- 11506816
TI  - Mechanism of up-regulated gap junctional intercellular communication during
      chemoprevention and chemotherapy of cancer.
AB  - To develop a strategy for efficacious intervention in order to prevent or treat
      various cancers, one must understand the basic mechanism(s) by which various
      anticancer dietary factors prevent or reverse the tumor promotion or progression
      phases. Carcinogenesis is a multistage, multimechanism process, involving the
      irreversible alteration of a stem cell (the "initiation" phase), followed by the
      clonal proliferation of the initiated stem cell (the "promotion" phase), from
      which the acquisition of the invasive and metastatic phenotypes are generated
      (the "progression" phase). While intervention to prevent or treat cancer could
      occur at each step, the objective of this presentation will focus on the rate
      limiting step, the promotion phase.Gap junctional intercellular communication
      (GJIC) has been hypothesized to regulate growth control, differentiation and
      apoptosis. Most normal, contact-inhibited cells have functional GJIC, while most,
      if not all, tumor cells have dysfunctional homologous or heterologous GJIC.
      Cancer cells are characterized by the lack of growth control, by the inability to
      terminally differentiate and by resistance to apoptosis. Chemical tumor promoters
      (phorbol esters, DDT, phenobarbital, unsaturated fatty acids, saccharin, etc.)
      inhibit GJIC in a reversible fashion and at doses above particular chemical
      thresholds. Various oncogenes (e.g. ras, raf, neu, src, mos) down-regulate GJIC
      while several tumor suppressor genes can up-regulate GJIC. Antitumor promoters
      (retinoids, carotenoids, green tea components) and antioncogene drugs (i.e.
      lovastatin) can up-regulate GJIC. Transfection of gap junction genes
      ("connexins") into GJIC-deficient tumor cells can restore GJIC, growth control
      and reduce tumorigenicity. On the other hand, antisense gap junction genes can
      convert the phenotype of a non-tumorigenic cell to that of a tumorigenic one.
      Recently, a specific connexin knockout mouse was shown to have a higher frequency
      of spontaneous and induced liver cancers. Evidence from these studies clearly
      suggests that dietary factors can modulate GJIC by inducing various signal
      transducing systems. The modulation can either down-regulate GJIC and lead to
      tumor promotion or it can up-regulate GJIC and lead to suppression of the
      initiated cells. Multiple mechanisms of up- or down-regulation of GJIC exist, as
      well as multiple types of pre-malignant and malignant tumor cells that are unable
      able to have functional GJIC. GJIC can be down-regulated by mutations and by
      epigenetic means. Alteration of gene expression at the transcriptional,
      translational or post-translational levels would require specific dietary
      prevention or treatment of cancer. In conclusion, if dietary prevention or
      treatment of cancer is to occur, it must ameliorate the growth-stimulatory
      effects, above threshold levels, of chemicals, growth factors or hormones, that
      trigger various mitogenic/antiapoptotic signal transducing systems that block
      GJIC.

PMID- 11506817
TI  - Signal transduction events elicited by cancer prevention compounds.
AB  - Many chemopreventive agents have been shown to modulate gene expression including
      induction of phase II detoxifying enzymes, such as glutathione S-transferases
      (GST) and quinone reductases (QR). Induction of phase II enzymes in general leads
      to protection of cells/tissues against exogenous and/or endogenous carcinogenic
      intermediates. The antioxidant or electrophile response element (ARE/EpRE) found
      at the 5'-flanking region of these phase II genes may play important role in
      mediating their induction by xenobiotics including chemopreventive agents.
      Members of the basic leucine zipper (bZIP) transcription factor, Nrf2 which
      heterodimerizes with Maf G/K, are found to bind to the ARE, and transcriptionally
      activated ARE. Recently, we showed that the mitogen-activated protein kinases
      (MAPK) were activated by phase II gene inducers such as phenolic antioxidant
      butylated hydroxyanisol (BHA) and isothiocyanate sulforaphane (SUL), and involved
      in the transcription activation of ARE-mediated reporter gene. Transfection
      studies with wild-type and dominant negative mutants of Nrf2 and MAPK showed
      synergistic response during co-transfection as well as to phase II gene inducers.
      However, increasing the concentrations of these compounds such as BHA, the
      activities of cell death signaling molecules, caspases, were stimulated and
      resulted in apoptotic cell death. At these concentrations, BHA stimulated loss of
      mitochondrial membrane potential, cytochrome c release, and activation of caspase
      3, 8 and 9 preceding apoptosis. Further increase in concentrations led to rapid
      cell necrosis. A model is proposed for BHA and SUL, in that at low
      concentrations, these potential chemopreventive agents may modulate MAPK pathway
      leading to transcription activation of Nrf2 and ARE with subsequent induction of
      cellular defensive enzymes including phase II detoxifying enzymes as well as
      other defensive genes, which may protect the cells against cellular injury, which
      is a homeostatic response. At higher concentrations, these agents may activate
      the caspase pathways, leading to apoptosis, a potential beneficial effect if
      occurs at preneoplastic/neoplastic tissues, but a potential cytotoxic response if
      occurs in normal tissues. On the other hand, some phenolic compounds such as
      resveratrol inhibits TPA- or UV-induced AP-1-mediated activity through the
      inhibition of c-Src non-receptor tyrosine kinase and MAPK pathways. It is
      possible that in proliferating or stimulated cells, these chemopreventive
      compounds may block proliferation by inhibiting these signaling kinases, whereas
      in non-proliferating or quiescent cells, some of these compounds may activate
      these signaling kinases leading to gene expression of cellular defensive enzymes
      such as phase II detoxifying enzymes. The studies of these and other signaling
      pathways may yield insights into the development of potential chemopreventive
      compounds.

PMID- 11506818
TI  - Molecular mechanisms underlying chemopreventive activities of anti-inflammatory
      phytochemicals: down-regulation of COX-2 and iNOS through suppression of NF-kappa
      B activation.
AB  - A wide array of phenolic substances, particularly those present in edible and
      medicinal plants, have been reported to possess substantial anticarcinogenic and
      antimutagenic activities. The majority of naturally occurring phenolics retain
      antioxidative and anti-inflammatory properties which appear to contribute to
      their chemopreventive or chemoprotective activity. Cyclooxygenase-2 (COX-2)
      inducible and nitric oxide synthase (iNOS) are important enzymes that mediate
      inflammatory processes. Improper up-regulation of COX-2 and/or iNOS has been
      associated with pathophysiology of certain types of human cancers as well as
      inflammatory disorders. Since inflammation is closely linked to tumor promotion,
      substances with potent anti-inflammatory activities are anticipated to exert
      chemopreventive effects on carcinogenesis, particularly in the promotion stage.
      Examples are curcumin, a yellow pigment of turmeric (Curcuma longa L.,
      Zingiberaceae), the green tea polyphenol epigallocatechin gallate (EGCG), and
      resveratrol from grapes (Vitis vinifera, Vitaceae) that strongly suppress tumor
      promotion. Recent studies have demonstrated that eukaryotic transcription factor
      nuclear factor-kappa B (NF-kappa B) is involved in regulation of COX-2 and iNOS
      expression. Several chemopreventive phytochemicals have been shown to inhibit COX
      2 and iNOS expression by blocking improper NF-kappa B activation. Multiple lines
      of compelling evidence indicate that extracellular-regulated protein kinase and
      p38 mitogen-activated protein kinase are key elements of the intracellular
      signaling cascades responsible for NF-kappa B activation in response to a wide
      array of external stimuli. Curcumin, EGCG and resveratrol have been shown to
      suppress activation of NF-kappa B. One of the plausible mechanisms underlying
      inhibition of NF-kappa B activation by aforementioned phytochemicals involves
      repression of degradation of the inhibitory unit I kappa B alpha, which hampers
      subsequent nuclear translocation of the functionally active subunit of NF-kappa
      B.

PMID- 11506819
TI  - Dietary supplementation with the anti-tumour promoter quercetin: its effects on
      matrix metalloproteinase gene regulation.
AB  - Dietary modification, especially the consumption of larger amounts of fruits and
      vegetables can act to decrease the risk of a variety of human cancers. Quercetin,
      a bioflavonoid widely distributed in fruits and vegetables has been shown to have
      a chemoprotective role in cancer, through complex effects on signal transduction
      involved in cell proliferation and angiogenesis. In this study we examined the
      effects of dietary supplementation of quercetin (30 mg per day) incorporated into
      a black currant drink. Healthy male subjects aged between 33 and 64 years
      (mean=47.1 years) received either quercetin or placebo for 14 days. Blood samples
      were taken at baseline and upon completion of the study and analysed for full
      blood count, matrix metalloproteinase-2 (MMP-2), tissue inhibitor of matrix
      metalloproteinse-1 and -2 (TIMP-1 and -2) plasma levels using ELISA techniques.
      RNA was extracted from the peripheral blood lymphocytes and reverse transcriptase
      polymerase chain reaction (RT-PCR) carried out for MMP-2 and TIMP-1, TIMP-2 gene
      expression determination. Supplementation of the diet with quercetin did not
      alter the MMP-2 or TIMP-2 gene transcription or plasma protein levels of the
      healthy subjects in this study. The TIMP-1 gene transcription and plasma protein
      levels (311+/-70 ng/ml at baseline to 183+/-35 ng/ml post-supplementation,
      P<0.05) of the subjects in this study were, however, significantly decreased
      following quercetin supplementation. This is an interesting result, as there is
      some controversy over the functions of TIMP-1 in tumour progression. In certain
      model systems, artificially increased TIMP-1 levels prevent or decrease tumour
      growth. However, in other studies high levels of TIMP-1 have been correlated with
      aggressive disease and poor prognosis in patients with certain malignancies. This
      study has outlined a potential role for the anti-tumour promoter quercetin as a
      dietary mediator of the carcinogenic cascade.

PMID- 11506820
TI  - The HAP1 protein stimulates the turnover of human mismatch-specific thymine-DNA
      glycosylase to process 3,N(4)-ethenocytosine residues.
AB  - When present in DNA, 3,N(4)-ethenocytosine (epsilon C) residues are potentially
      mutagenic and carcinogenic in vivo. The enzymatic activity responsible for the
      repair of the epsilon C residues in human cells is the hTDG protein, the human
      thymine-DNA-glycosylase that removes thymine in a T/G base pair [Proc. Natl.
      Acad. Sci., U.S.A., 95 (1998) 8508]. One of the distinctive properties of the
      hTDG protein is that it remains tightly bound to the AP-site resulting from its
      glycosylase activity. In this paper we report that the human AP endonuclease, the
      HAP1 (Ape1, APEX Ref-1) protein, stimulates the processing of epsilon C residues
      by the hTDG protein in vitro, in a dose-dependent manner. This property of HAP1
      protein is specific since E.coli Fpg, Nfo and Nth proteins, all endowed with an
      AP nicking activity, do not show similar features. The results suggest that the
      HAP1 protein displaces the hTDG protein bound to the AP-site and therefore
      increases the turnover of the hTDG protein. However, using a variety of
      techniques including gel retardation assay, surface plasmon resonance and two
      hybrid system, it was not possible to detect evidence for a complex including the
      substrate, the hTDG and HAP1 proteins.

PMID- 11506821
TI  - Effects of cruciferous vegetables and their constituents on drug metabolizing
      enzymes involved in the bioactivation of DNA-reactive dietary carcinogens.
AB  - Epidemiological studies give evidence that cruciferous vegetables (CF) protect
      humans against cancer, and also results from animal experiments show that they
      reduce chemically induced tumor formation. These properties have been attributed
      to alterations in the metabolism of carcinogens by breakdown products of
      glucosinolates, which are constituents of CF. The present article gives an
      overview on the present state of knowledge on the impact of CF and their
      constituents on enzymes that are involved in the metabolism of DNA-reactive
      carcinogens. The development of in vitro models with metabolically competent cell
      lines led to the detection of potent enzyme inducers contained in CF such as
      sulforaphane. Recently, we showed that Brassica juices induce glutathione-S
      transferases (GST) and cytochrome P-450 1A2 in human hepatoma cells (HepG2) and
      protect against the genotoxic effects of B(a)P and other carcinogens. Earlier in
      vivo experiments with rodents indicated that indoles and isothiocyanates, two
      major groups of glucosinolate breakdown products, attenuate the effects of
      polycyclic aromatic hydrocarbons (PAHs) and nitrosamines via induction of GST and
      inhibition of cytochrome-P450 isoenzymes, respectively. Our own investigations
      showed that CF are also protective towards heterocyclic amines (HAs): Brussels
      sprouts- and garden cress juices attenuated IQ-induced DNA-damage and
      preneoplastic lesions in colon and liver of rats. These effects were paralleled
      by induction of uridine-di-phospho-glucuronosyl transferase (UDPGT) which is very
      probably the mechanism of protection against HAs by cruciferous vegetables. There
      is also evidence that consumption of CF might protect humans against cancer. In
      matched control intervention studies with these vegetables, it was shown that
      they induce GST-activities in humans but overall, results were inconclusive.
      Recently, we carried out crossover intervention studies and found pronounced GST
      induction upon consumption of Brussels sprouts and red cabbage, whereas no
      effects were seen with white cabbage and broccoli. Furthermore, we found that the
      isoenzyme induced was GST-pi which plays an important role in protection against
      breast, bladder, colon and testicular cancer. No induction of the GST-alpha
      isoform could be detected. Urinary mutagenicity experiments gave further evidence
      that CF affect drug metabolism in humans. Consumption of red cabbage led to
      changes in the pattern of meat-derived urinary mutagenicity. Overall, CF are
      among the most promising chemopreventive dietary constituents and further
      elucidation of their protective mechanisms and the identification of active
      constituents may contribute to the development of highly protective Brassica
      varieties.

PMID- 11506822
TI  - Cancer prevention with green tea and monitoring by a new biomarker, hnRNP B1.
AB  - The study of green tea polyphenols as a cancer preventative is approaching a new
      era, with significant results accumulating rapidly. This paper briefly reviews
      four topics related to mechanisms of action of tea polyphenols: (I)
      identification of the genes commonly affected by EGCG, as demonstrated by
      Clontech's Atlas cDNA Expression Array; (II) the significance of heterogeneous
      nuclear ribonucleoprotein B1 (hnRNP B1) as a new biomarker for early detection of
      lung cancer, and inhibition of its expression by EGCG; (III) the synergistic or
      additive effects of EGCG with the cancer preventive agents, sulindac and
      tamoxifen, on induction of apoptosis in PC-9 cells and on inhibition of
      intestinal tumor development in multiple intestinal neoplasia (Min) mice; (IV)
      the results of a 10 year prospective cohort study demonstrating the effectiveness
      of daily consumption of green tea in preventing cancer, and a prototype study for
      developing green tea beverage as cancer preventive.

PMID- 11506823
TI  - Role of phase 2 enzyme induction in chemoprotection by dithiolethiones.
AB  - One of the major mechanisms of protection against carcinogenesis, mutagenesis,
      and other forms of toxicity mediated by carcinogens is the induction of enzymes
      involved in their metabolism, particularly phase 2 enzymes such as glutathione S
      transferases (GSTs), UDP-glucuronosyl transferases, and quinone reductases.
      Animal studies indicate that induction of phase 2 enzymes is a sufficient
      condition for obtaining chemoprevention and can be achieved by administering any
      of a diverse array of naturally-occurring and synthetic chemopreventive agents.
      Indeed, monitoring of enzyme induction has led to the recognition or isolation of
      novel, potent chemopreventive agents such as 1,2-dithiole-3-thiones, terpenoids
      and the isothiocyanate sulforaphane. For example, oltipraz, a substituted 1,2
      dithiole-3-thione originally developed as an antischistosomal agent, possesses
      chemopreventive activity against different classes of carcinogens targeting
      multiple organs. Mechanistic studies in rodent models for chemoprevention of
      aflatoxin B(1) (AFB(1))-induced hepatocarcinogenesis by oltipraz indicates that
      increased expression of phase 2 genes is of central importance, although
      inhibition of phase 1 activation of AFB(1) can also contribute to protection.
      Exposure of rodents to 1,2-dithiole-3-thiones triggers nuclear accumulation of
      the transcription factor Nrf2 and its enhanced binding to the "antioxidant
      response element" (ARE), leading to transcriptional activation of a score of
      genes involved in carcinogen detoxication and attenuation of oxidative stress.
      Nrf2-deficient mice fail to induce many of these genes in response to
      dithiolethiones; moreover, basal expression of these genes is typically
      repressed. To test the hypothesis that enzyme induction is a useful strategy for
      chemoprevention in humans, three key elements are necessary: a candidate agent,
      an at-risk population and modulatable intermediate endpoints. Towards this end, a
      placebo-controlled, double blind clinical trial of oltipraz was conducted in
      residents of Qidong, PR China who are exposed to dietary aflatoxins and who are
      at high risk for the development of liver cancer. Oltipraz significantly enhanced
      excretion of a phase 2 product, aflatoxin-mercapturic acid, a derivative of the
      aflatoxin-glutathione conjugate, in the urine of study participants administered
      125 mg oltipraz by mouth daily. Administration of 500 mg oltipraz once a week led
      to a significant reduction in the excretion of the primary oxidative metabolite
      of AFB(1), AFM(1), when measured shortly after drug administration. While this
      study highlighted the general feasibility of inducing phase 2 enzymes in humans,
      a longer term intervention is addressing whether protective alterations in
      aflatoxin metabolism can be sustained for extended periods of time in this high
      risk population.

PMID- 11506824
TI  - Developing sustainable studies on environmental health.
AB  - Toxicogenetics, toxicogenomics and proteomics are providing new biomarkers for
      use in human studies. These, coupled with the more traditional biological
      responses currently in use, provide a vast armamentarium for assessing exposures,
      effects and susceptibility factors relating to environmental pollutants.
      Biomarker availability, however, does not automatically translate to usefulness
      for studies directed at human health improvement. Transitional studies bridging
      the gap between laboratory and field, with the biomarker as dependent variable,
      are required for validation for intended applications. Prospective or cross
      sectional studies are usually optimal for validating biomarkers of exposure,
      where the biomarker response follows the event (exposure) and the entire study
      population is affected. Biomarkers of effect, where the event (outcome) follows
      the biomarker response and may be infrequent in the study population, present
      more complex problems. Identification of genotypes as susceptibility factors
      requires that additional issues be addressed. Despite these difficulties, new
      data are emerging from transitional investigations that are providing validated
      biomarkers for sustainable human studies. It is now possible to envision schemes
      for integrating the results of molecular epidemiological investigations into the
      general toxicological evaluations of environmental agents. These will allow
      intermediate endpoints to be used for making realistic human health assessments
      and for elucidating pathogenic mechanisms that identify targets for intervention,
      all with the goal of preventing environmentally mediated human disease. Finally,
      select biomarker responses that predict the likelihood of disease occurrence will
      find application in the interpretation of individual medical diagnostic tests,
      with the goal of improving cancer detection and management.

PMID- 11506825
TI  - Ethical and practical aspects of human studies.
AB  - Increasingly, genetic information holds the promise of prevention, earlier
      detection, and better treatment for cancer and other genetically related
      diseases. Laboratory markers are giving insight into the role of measurable
      genetic changes; however, there is often difficulty in translating laboratory
      data into practical use in human populations. Human populations can be difficult
      to study, and, correctly, there are strict regulations regarding the use of
      humans as study subjects for many kinds of research activities. Various study
      designs have a differential ability to prove cause and effect relationships, and
      will similarly have a differential ability in validating the usefulness of
      genetic markers. Just as conducting bench research has a traditional set of
      problems, working with human populations has its own set of potential
      difficulties. In reality, workers and others are often exposed to carcinogenic
      substances, usually without their knowledge, and without their informed consent.
      As genetic information becomes more readily available, and in finer detail, there
      is a great risk of misuse by employers, insurance companies and others. Placing
      blame on someone's genetic make-up may once again put into vogue a "blame-the
      victim" mentality instead of continuing efforts to clean up workplaces and the
      environment, or restricting the use of hazardous products. No genetic information
      should ever be used to deny employment or modify insurance rates. Individuals
      should be able to maintain personal control over their genetic information.
      Positive aspects of the use of genetic information can be used to decrease
      disease and make environments safer.

PMID- 11506826
TI  - Factors that contribute to biomarker responses in humans including a study in
      individuals taking Vitamin C supplementation.
AB  - It is possible in many situations to identify humans exposed to potentially toxic
      materials in the workplace and in the environment. As in most human studies,
      there tends to be a high degree of interindividual variability in response to
      chemical insults. Some non-exposed control individuals exhibit as high a level of
      damage as some exposed individuals and some of these have levels of damage as low
      as many of the controls. Thus, it is only the mean values of the groups that can
      substantiate an exposure-related problem; the data on an individual basis are
      still of limited use. While human lymphocytes remain the most popular cell type
      for monitoring purposes, sperm, buccal, nasal, epithelial and placental cells are
      also used. However, for interpretation of responses, the issue of confounding
      factors must be addressed. There are endogenous confounding factors, such as age,
      gender, and genetic make-up and exogenous ones, including lifestyle habits
      (smoking, drinking, etc.) There are biomarkers of exposure, effect/response and
      susceptibility and the last may be influenced by the genotype and polymorphism
      genes existing in a population. From our own studies, confounding effects on
      cytogenetic damage and ras oncoproteins will be considered in relation to workers
      exposed to vinyl chloride and petroleum emissions and to volunteers taking
      Vitamin C supplementation. Smoking history, exposure and duration of employment
      affected the worker studies. For petroleum emissions, so did gender and season of
      exposure. For the non-smoking volunteer Vitamin C supplementation study,
      cholesterol levels, plasma Vitamin C levels, lipid peroxidation products and DNA
      damage in the Comet assay were also measured. Gender affected differences in
      Vitamin C levels, antioxidant capacity and the number of chromosome aberrations
      induced by bleomycin challenge in vitro. The results were the same for both high
      and low cholesterol subjects. The relationship between biomarkers and the various
      factors which affect them is complex. Sometimes the variables are not completely
      independent of each other.

PMID- 11506827
TI  - Validation of biomarkers as early predictors of disease.
AB  - The development and validation of biomarkers that link environmental exposures to
      the pathogenesis of human disease is a leading priority in the field of
      environmental research. The validation of biomarkers as early predictors of
      clinical disease can enhance health risk assessment and contribute to effective
      new disease prevention policies in environmental and occupational settings. The
      process of validating biomarkers involves dealing with a range of characteristics
      that include the intrinsic qualities of the biomarker, its determinants, and the
      analytic procedure. We discuss here a three phase approach to validation. The
      final phase, consisting of longitudinal studies, is reached after the biomarker
      has been determined to be technically reliable and after the effect of external
      variables on the association with the outcome has been evaluated. We provide some
      examples of biomarkers reputed to be early predictors of cancer and
      cardiovascular disease (CVD). We then present original data to support the
      potential of DNA adducts to predict cancer and show, through re-evaluation of the
      Italian database on cytogenetic biomarkers, a lack of association between the
      frequency of chromosomal aberrations in circulating lymphocytes and CVD mortality
      rates -- a finding that should not be considered conclusive. In general, whenever
      a biomarker has been determined to be a valid predictor of disease, it should be
      used in risk assessment and public health policy.

PMID- 11506828
TI  - The role of bile acids in carcinogenesis.
AB  - Bile acids play a role in colorectal carcinogenesis as evidenced by
      epidemiological and experimental studies. Some bile acids stimulate growth of
      normal colonic and adenoma cells, but not of colorectal cancer cells. Moreover,
      bile acids stimulate invasion of colorectal cancer cells, at least in vitro. One
      possible mechanism of action is bile acid-induced DNA binding and transactivation
      of the activator protein-1 (AP-1) by co-operate activation of extracellular
      signal-regulated kinases (ERKs) and PKC signaling. In the present paper, we
      review the mechanisms by which bile acids influence carcinogenesis.

PMID- 11506829
TI  - Oxidative DNA damage induced by high glucose and its suppression in human
      umbilical vein endothelial cells.
AB  - In order to investigate the mechanism of the production of oxidative DNA damage
      by hyperglycemia, we measured formamidopyrimidine N-glycosylase (FPG)-sensitive
      sites by the comet assay in human umbilical vein endothelial cells (HUVECs)
      cultured under various conditions including high glucose. Mean values of FPG
      sensitive sites were higher in HUVECs cultured for 5 days in high glucose (45 mM)
      compared with normal glucose (5mM) medium (P<0.001). FPG-sensitive sites
      increased in a time-dependent manner under high glucose treatment (3 days:
      P<0.05, 5 days: P<0.001), whereas L-glucose, which is taken up poorly into the
      cells, gave a slight increase in FPG-sensitive sites (P<0.05). Flow cytometric
      analysis using 6-carboxy-2',7'-dichlorodihydrofluorescein diacetate,
      di(acetoxymethyl ester) showed that incubation with L-glucose produced more
      reactive oxygen species than incubation with D-glucose. However, these increases
      were slight (1.22- and 1.12-folds, respectively). Incubation of HUVECs with
      aminoguanidine (100 microM) or pyridoxamine (1mM), which are inhibitors of
      glycation, decreased the levels of FPG-sensitive sites (P<0.001). However, these
      inhibitors did not suppress the intracellular generation of reactive oxygen
      species induced by high glucose. These results indicate that FPG-sensitive sites
      induced by high glucose are not due to intracellular reactive oxygen species. In
      order to clarify what caused the induction of FPG-sensitive sites, we
      investigated the effect of glyoxal and 3-deoxyglucosone (3-DG) on the induction
      of FPG-sensitive sites and the intracellular production of reactive oxygen
      species in HUVECs. Glyoxal and 3-DG at a concentration of 100 microg/ml induced
      FPG-sensitive sites (P<0.001, P<0.01, respectively). In contrast, glyoxal did not
      generate reactive oxygen species inside HUVECs. The results shown in this study
      suggest that glyoxal formed intracellularly or extracellularly during high
      glucose treatment might induce FPG-sensitive sites by a mechanism not involving
      reactive oxygen species.

PMID- 11506831
TI  - Professional liability--storm warning.

PMID- 11506833
TI  - Anterior or posterior sacrospinous vaginal vault suspension: long-term anatomic
      and functional evaluation.
AB  - OBJECTIVE: To compare vaginal anatomy and sexual function after the conventional
      posterior and anterior sacrospinous vault suspension. METHODS: A retrospective
      repeated measures cohort study included all 168 consecutive sacrospinous vault
      suspension procedures between July 1990 and February 1997. The posterior
      suspension (n = 92) used a posterior vaginal incision and pararectal dissection.
      Anterior suspension (n = 76) involved an anterior rather than posterior vaginal
      incision, retropubic perforation, and dissection of a paravaginal-paravesical
      rather than pararectal space to accommodate the vaginal vault. Two
      polytetrafluoroethylene (00) sutures anchored the anterior vaginal cuff (for the
      anterior sacrospinous suspension) or the posterior vaginal cuff (for the
      posterior sacrospinous suspension) to the ligament. Postoperative evaluation
      included an examination using the pelvic organ prolapse quantitative system,
      assessment of vaginal width and axis, and symptom questionnaire. RESULTS: Total
      vaginal length and apical suspension were slightly greater after the anterior
      suspension, and recurrent anterior vaginal relaxation was less likely. No
      differences were found in maximal dilator size or apical narrowing between the
      two groups. New onset dyspareunia was reported by two subjects in the anterior
      vault suspension group, and two in the posterior vault suspension group. Three of
      these four cases of de novo dyspareunia were attributable to either severe
      atrophy or recurrent prolapse, and none to vaginal narrowing or shortening.
      CONCLUSION: After anterior sacrospinous vault suspension, vaginal length and
      apical suspension were slightly increased, and recurrent anterior vaginal
      prolapse decreased compared with the posterior sacrospinous suspension technique.
      Upper vaginal caliber and sexual function appear well preserved using either
      technique.

PMID- 11506834
TI  - Low-dosage esterified estrogens opposed by progestin at 6-month intervals.
AB  - OBJECTIVE: To estimate incidence of endometrial hyperplasia, vaginal bleeding,
      and menopausal symptoms in women who changed from standard monthly cyclic hormone
      replacement therapy (HRT) to half-strength estrogen opposed by
      medroxyprogesterone acetate (MPA) at 6-month intervals. METHODS: We identified
      138 women aged 55-75 years who had regularly used HRT at a standard dosage
      (equivalent to 0.625 mg conjugated estrogen) opposed by cyclic monthly MPA. Each
      subject's HRT regimen was changed to 0.3 mg/day esterified estrogens (Estratab;
      Solvay Pharmaceuticals, Marietta, GA) combined with 14-day courses of MPA, 10
      mg/day, every 6 months. Endometrial biopsy was repeated after 1 year of the new
      regimen. Any vaginal bleeding was reported in each patient's daily diary.
      Menopause symptoms were evaluated using the Greene Menopause Symptom Index.
      RESULTS: Among 125 women who had biopsy after 1 year of the new regimen,
      endometrial hyperplasia was found in two (1.6%, 95% confidence interval 0.3%,
      6.2%). Of the 125 women, 44% had scheduled bleeding, and 9.4% had unscheduled
      bleeding. Relative to baseline vasomotor score (range 0-6), an increase of at
      least 2 U was reported by 20% of subjects at 6 months and by 17% of subjects at
      12 months. CONCLUSION: Most women aged at least 55 years can safely switch their
      HRT regimen from standard dosage HRT to low-dosage estrogen opposed by MPA at 6
      month intervals. Moreover, this new HRT regimen causes little vaginal bleeding
      while maintaining adequate control of menopausal symptoms.

PMID- 11506835
TI  - Symptoms of ovarian cancer.
AB  - OBJECTIVE: To examine the symptoms of ovarian cancer in patients compared with
      symptoms experienced by healthy women using a case-control design. METHODS: Cases
      (n = 168) were women with ovarian cancer diagnosed at two hospitals in New York
      between 1994 and 1997 who were interviewed shortly after diagnosis. They were
      compared with healthy women (n = 251 controls) from the community. Women were
      asked about the prevalence, duration, and constancy of eight symptoms and about
      use of three types of medications in the 6 to 12 months before diagnosis (cases)
      or interview (controls). RESULTS: Nearly all the cases (93%) reported at least
      one symptom, compared with 42% of controls. The most common symptoms among cases
      were: unusual bloating, fullness, and pressure in the abdomen (71%); unusual
      abdominal pain or lower back pain (52%); and lack of energy (43%). The
      proportions of controls reporting these symptoms were 9, 15, and 16%,
      respectively, resulting in odds ratios and 95% confidence intervals of 25.3
      (15.6, 40.9), 6.2 (4.0, 9.6), and 3.9 (2.5, 6.1), respectively, for these
      symptoms. Bloating, fullness, and pressure was of more recent onset among cases
      than controls (4.9 months compared with 7.6 months, P =.01). There were only
      minor differences in reported symptoms between cases with early and later stage
      disease. CONCLUSION: Unusual bloating, fullness, and pressure, abdominal or back
      pain, and lack of energy are prominent symptoms in women with ovarian cancer and
      distinguish them from controls. Information on symptoms may make women and
      physicians more aware of changes associated with ovarian cancer.

PMID- 11506836
TI  - Evaluation of interaction between fluconazole and an oral contraceptive in
      healthy women.
AB  - OBJECTIVE: To evaluate the potential pharmacokinetic interaction between 2 x 150
      mg fluconazole administered once weekly and an oral contraceptive (OC) containing
      ethinyl estradiol and norethindrone. METHODS: A placebo-controlled, double
      masked, randomized, two-way crossover study was used to investigate the
      pharmacokinetic interaction between 300 mg fluconazole once weekly and the OC
      Ortho Novum 7/7/7 (Ortho-McNeil Pharmaceutical, Inc., Raritan, NJ) in 26 healthy
      women, 18-36 years old. In the first cycle (28 days), subjects received OC only.
      In the second cycle, subjects were assigned randomly to receive OC-fluconazole or
      OC-placebo. In the third cycle, subjects were crossed over to the opposite
      treatment. RESULTS: Data for 21 subjects who completed the study were included in
      the pharmacokinetic analysis; data for all 26 subjects were included in the
      safety analysis (26 OC only; 24 OC-fluconazole; 23 OC-placebo). Treatment with OC
      fluconazole resulted in small but statistically significant increases in 0-24
      hour area under the plasma concentration-time curve (AUC(0-24)) for both ethinyl
      estradiol (mean 24%, 95% confidence interval [CI] 18%, 31%) and norethindrone
      (mean 13%, 95% CI 8%, 18%) as compared with treatment with OC-placebo. Ethinyl
      estradiol maximum plasma concentration (C(max)) was slightly (mean 8%, 95% CI 2%,
      15%) though statistically significantly higher for OC-fluconazole treatment as
      compared with OC-placebo treatment. Norethindrone C(max) was not different (95%
      CI -6%, 11%) between the two treatment groups. No adverse events related to
      treatment were seen in the fluconazole treatment group. CONCLUSION: The
      concomitant administration of 300 mg fluconazole once weekly, twice the
      recommended dose for vaginal candidiasis, to women using OCs results in a slight
      increase in OC concentrations. Therefore, it appears that there is no threat of
      contraceptive failure because of concomitant fluconazole administration.

PMID- 11506837
TI  - Obstetric anal sphincter lacerations.
AB  - OBJECTIVE: To estimate the frequency of obstetric anal sphincter laceration and
      to identify characteristics associated with this complication, including
      modifiable risk factors. METHODS: A population-based, retrospective study of over
      2 million vaginal deliveries at California hospitals was performed, using
      information from birth certificates and discharge summaries for 1992 through
      1997. We excluded preterm births, stillbirths, breech deliveries, and multiple
      gestations. The main outcome measure was obstetric anal sphincter laceration
      (third and fourth degree). RESULTS: The frequency of anal sphincter lacerations
      was 5.85% (95% confidence interval [CI] 5.82, 5.88), decreasing significantly
      from 6.35% (95% CI 6.27, 6.43) in 1992 to 5.43% (95% CI 5.35, 5.51) in 1997 (P
      <.01). Using logistic regression analysis, we identified primiparity as the
      dominant risk factor (odds ratio [OR] for women with prior vaginal birth 0.15;
      95% CI 0.14, 0.15). Birth weight over 4000 g was also highly significant (OR
      2.17; 95% CI 2.07, 2.27). Lacerations occurred more often among women of certain
      racial and ethnic groups: Indian women (OR 2.5; 95% CI 2.23, 2.79) and Filipina
      women (OR 1.63; 95% CI 1.50, 1.77) were at highest risk. Episiotomy decreased the
      likelihood of third-degree lacerations (OR 0.81; 95% CI 0.78, 0.85), but
      increased the risk of fourth-degree lacerations (OR 1.12; 95% CI 1.05, 1.19).
      Operative delivery increased the risk of sphincter laceration, with vacuum
      delivery (OR 2.30; 95% CI 2.21, 2.40) presenting a greater risk than forceps
      delivery (OR 1.45; 95% CI 1.37, 1.52). CONCLUSION: Anal sphincter lacerations are
      strongly associated with primiparity, macrosomia, and operative vaginal delivery.
      Of the modifiable risk factors, operative vaginal delivery remains the dominant
      independent variable.

PMID- 11506838
TI  - Risk of fetal loss in twin pregnancies undergoing second trimester
      amniocentesis(1).
AB  - OBJECTIVE: To assess the rate of fetal loss among bichorionic twin gestations
      undergoing genetic amniocentesis compared with singletons undergoing the
      procedure and untested twins. METHODS: In a retrospective cohort study, three
      groups were compared: 476 women with twins undergoing amniocentesis, 489 women
      with singleton gestations undergoing amniocentesis, and 477 women with twins
      presenting at a similar gestational age for ultrasound studies only. All subjects
      were scanned at 17-18 weeks' gestation and again approximately 4 weeks after the
      procedure or first ultrasound scan. Excluded were twin pregnancies after fetal
      reduction or chorionic villus sampling, fetuses with structural anomalies, and
      cases in which one fetus had died at the time of examination or after fetal
      reduction. RESULTS: Thirteen twin gestations in the tested group (2.73%) aborted
      spontaneously up to 4 weeks after the procedure compared with three twin controls
      (0.63%, P =.01) and three post-procedure singleton controls (0.6%, P =.01). An
      abnormal karyotype was discovered in 15 tested twin pregnancies (3%) and in six
      tested singletons (1.23%). All affected twin pairs were discordant for the
      chromosomal anomaly. CONCLUSION: The risk of early fetal loss in twins undergoing
      amniocentesis appears to be higher than that of exposed singletons or unexposed
      twins.

PMID- 11506839
TI  - Uterine artery Doppler in predicting pregnancy outcome in women with
      antiphospholipid syndrome.
AB  - OBJECTIVE: To assess midtrimester uterine artery Doppler in the prediction of
      preeclampsia and small for gestational age (SGA) infants in women with primary
      antiphospholipid syndrome. METHODS: One hundred seventy pregnant women with
      histories of recurrent miscarriage in association with antiphospholipid
      antibodies (32 lupus anticoagulant positive, 47 IgG anticardiolipin positive, 78
      IgM anticardiolipin positive, and 13 lupus anticoagulant and anticardiolipin
      antibodies positive) treated with low-dose aspirin and heparin were recruited
      prospectively. Doppler assessment of the uterine arteries (presence or absence of
      notches and pulsatility index) were performed at 16-18 and 22-24 weeks. The main
      outcome measures were the delivery of a SGA infant and the development of
      preeclampsia. RESULTS: There were 164 live births and six midtrimester losses.
      The prevalence of preeclampsia and SGA was similar at 10%. In predicting
      preeclampsia or SGA, uterine artery pulsatility index at either interval was of
      no value, and the diagnostic accuracy of the Doppler was limited to bilateral
      uterine artery notches at 22-24 weeks in the subgroup of women with positive
      lupus anticoagulant. In this subgroup, bilateral uterine artery notches at 22-24
      weeks in predicting preeclampsia generated a high likelihood ratio for positive
      test (12.8, 95% confidence interval 2.2, 75), sensitivity (75%), specificity
      (94%), positive (75%) and negative (94%) predictive value. In predicting SGA, the
      corresponding figures were respectively 13.6 (95% confidence interval 1.9, 96),
      80%, 94%, 80%, 94%. Uterine artery Doppler was of limited value in pregnancies
      associated with anticardiolipin antibodies in isolation. CONCLUSION: In
      pregnancies associated with lupus anticoagulant, uterine artery Doppler at 22-24
      weeks is a useful screening test in predicting preeclampsia and SGA infants.

PMID- 11506840
TI  - Improved outcome of preterm infants when delivered in tertiary care centers.
AB  - OBJECTIVE: Previous studies that compared outcomes of infants born outside
      tertiary care centers (outborn) with those born in tertiary care centers (inborn)
      did not account for admission illness severity and perinatal risks. The objective
      of this study was to examine whether outborn status is associated with higher
      mortality and morbidity, after adjustment for perinatal risks and admission
      illness severity (using the Score for Neonatal Acute Physiology, Version II [SNAP
      II]) among preterm infants who were admitted to Neonatal Intensive Care Units
      (NICUs). METHODS: Logistic regression analysis was used to compare the risk
      adjusted outcomes of 3769 singleton infants born at or before 32 weeks'
      gestation, who were admitted to 17 Canadian NICUs during 1996-1997. RESULTS:
      Outborn and inborn infants had significantly different gestational ages,
      perinatal risk factors (maternal hypertension, prenatal care, antenatal
      corticosteroid therapy, 5-minute Apgar score, delivery type, small for
      gestational age) and admission SNAP-II. Outborn infants were at higher risk of
      death (adjusted odds ratio [OR] 1.7, 95% confidence interval [CI] 1.2, 2.5),
      grade III or IV intraventricular hemorrhage (adjusted OR 2.2, 95% CI 1.5, 3.2),
      patent ductus arteriosus (adjusted OR 1.6, 95% CI 1.2, 2.1), respiratory distress
      syndrome (adjusted OR 4.8, 95% CI 3.6, 6.3), and nosocomial infection (adjusted
      OR 2.5, 95% CI 1.9, 3.3), even after adjusting for perinatal risks and admission
      illness severity. CONCLUSIONS: Outborn infants were less mature and more ill than
      inborn infants at NICU admission. However, even after adjustment for perinatal
      risks and admission illness severity, inborn infants had better outcomes than
      outborn infants. Our results support in-utero transfer of high-risk pregnancies
      to a tertiary level facility.

PMID- 11506841
TI  - Comparison of microtransducer and fiberoptic catheters for urodynamic studies.
AB  - OBJECTIVE: To assess the validity and reproducibility of a fiberoptic transducer
      urodynamic catheter for urethral closure pressure profiles and leak point
      pressure determination, using a microtransducer catheter as the standard.
      METHODS: Ninety women without significant pelvic organ prolapse underwent
      urodynamic evaluations with both fiberoptic and microtransducer catheters.
      Maximal urethral closure pressures and "leak point pressures" were repeatedly
      measured by the two catheters and statistically compared. The order of catheter
      use was randomized. RESULTS: Significantly lower mean maximal urethral closure
      pressures were recorded by the fiberoptic system than by the microtransducer
      system (28.9 cmH(2)O +/- 17.3 versus 43.2 cmH(2)O +/- 24.9, P <.001). The
      fiberoptic catheter predicted microtransducer values for maximum urethral closure
      pressure only within a range of 27 cmH(2)O. Mean "leak point pressure" recorded
      by the fiberoptic catheters (66.9 cmH(2)O +/- 2.9) was not significantly
      different than that recorded by the microtransducer catheters (66.4 cmH(2)O +/-
      2.9, P =.97). CONCLUSION: There is a significant difference between maximum
      urethral closure pressure values recorded by the microtransducer and fiberoptic
      catheter systems. No significant difference was found between the two systems in
      measurement of Valsalva "leak point pressure."

PMID- 11506842
TI  - Development of an endometriosis quality-of-life instrument: The Endometriosis
      Health Profile-30.
AB  - OBJECTIVE: To describe a new disease-specific questionnaire with established
      measurement properties that addresses the dimensions of health-related quality of
      life considered important to women with endometriosis. METHODS: The Endometriosis
      Health Profile-30 was developed in three stages. Stage 1 included open-ended
      exploratory interviews with 25 women to generate the items on the questionnaire.
      Stage 2 was an 87-item questionnaire administered in a postal survey to identify
      the most salient dimensions of health-related quality of life. In stage 3, the
      reliability and validity of the questionnaire were evaluated. RESULTS: The final
      instrument contained a core questionnaire with 30 items and five scales: pain,
      control and powerlessness, emotional well-being, social support, and self-image.
      Six modular parts consisting of 23 questions were also developed and measured the
      areas of sexual intercourse, work, relationship with children, feelings about the
      medical profession, treatment, and infertility. All the scales achieved high
      internal reliability, with Cronbach's alpha coefficient ranging from 0.83 to 0.93
      (core questionnaire) and 0.79 to 0.96 (modules). The intraclass correlation
      coefficients to evaluate the test-retest reliability were high (range 0.88-0.98,
      P <.001). Content validity was demonstrated as the questionnaire was developed
      from interviews of patients rather than existing literature and clinical scales.
      Construct validity was assessed by correlating the Endometriosis Health Profile
      30 scales with the relevant Short Form-36 scales. High correlations for all
      comparisons were found (-0.41 to -0.73). CONCLUSION: The Endometriosis Health
      Profile-30 is a reliable, valid, patient-generated instrument to measure the
      health-related quality of life of women with endometriosis. Its application in
      various health care settings will provide new and valuable information on the
      effect of endometriosis on health-related quality of life from the patients'
      perspective.

PMID- 11506843
TI  - Functional and anatomic follow-up of enterocele repairs.
AB  - OBJECTIVE: To identify the functional and anatomic outcomes in women who have
      surgery for pelvic organ prolapse with enterocele repair. METHODS: Fifty-four
      women had surgery for pelvic organ prolapse which included enterocele repair.
      Preoperative and postoperative examinations were done by a research nurse,
      including a pelvic examination using the International Continence Society staging
      system and standardized questionnaires about bowel function, sexual function, and
      prolapse symptoms. RESULTS: Fifty-four women had enterocele repairs as part of
      their surgery. Mean follow-up time was 16 months (range 6-29 months).
      Postoperatively five women were excluded from the analysis because of fluctuation
      in stage of prolapse over time. At the apex and posterior wall of the vagina, 33
      women had stage 0 or I prolapse, and 16 had stage II prolapse. None had stage III
      or IV prolapse. Fifty-three percent of women had improvement in bowel function
      and 91% had improvement in vaginal prolapse symptoms. Functional outcomes were
      not significantly different in women with and without stage II prolapse at follow
      up. CONCLUSION: Most women who had surgery for pelvic organ prolapse with
      enterocele repair reported improvement in vaginal prolapse symptoms. Functional
      outcomes did not differ significantly between women with stage 0 and I prolapse
      and women with stage II prolapse at the vaginal apex and posterior vaginal wall.
      This was an observational study and the lack of statistically significant
      findings could result from inadequate sample size; however, the observed
      differences were judged to be not clinically significant.

PMID- 11506844
TI  - Self-reported Papanicolaou smears and hysterectomies among women in the United
      States.
AB  - OBJECTIVE: To evaluate the potential overuse of Papanicolaou smears among women
      who have had a hysterectomy. METHODS: We analyzed two surveys of US women aged 18
      years or older, the Behavioral Risk Factor Surveillance System (1992-1997) and
      the National Health Interview Survey (1993-1994), and one survey of US hospitals
      (National Hospital Discharge Survey, 1980-1997). We examined the number of women
      who have had a hysterectomy who had a recent (within 3 years) Papanicolaou smear.
      We also examined trends in the proportions and rates of hysterectomies by
      diagnoses and type of procedure that potentially could require a Papanicolaou
      smear. RESULTS: From the Behavioral Risk Factor Surveillance System, an estimated
      21.2% of US women have had a hysterectomy. Among women who have had a
      hysterectomy, 78.3% had a recent Papanicolaou smear. Among those reporting no
      hysterectomy, 82.1% had a recent Papanicolaou smear. Estimates from the National
      Health Interview Survey were similar. From the National Hospital Discharge
      Survey, an estimated 6.7% to 15.4% of women with a history of hysterectomy would
      require a subsequent Papanicolaou smear because they had a diagnosis related to
      cervical neoplasia or because they had undergone a supracervical hysterectomy.
      For an estimated 10.6-11.6 million of the 12.5 million women who had a
      hysterectomy and a recent Papanicolaou smear, that test could be considered
      unnecessary. CONCLUSION: Continued Papanicolaou screening of women without an
      intact uteri may result in excessive use of resources in time and money with
      minimal impact on decreasing cervical cancer.

PMID- 11506845
TI  - Second-trimester placental volume and infant size at birth.
AB  - OBJECTIVE: To investigate the ability of second-trimester placental volume
      measured sonographically to predict birth size. METHODS: A total of 712 women
      were recruited from the antenatal clinic of the University Hospital of the West
      Indies; 561 fulfilled the study criteria and progressed to delivery. Placental
      volume and fetal anthropometry (biparietal diameter, head and abdominal
      circumferences, and femoral length) were measured sonographically at 14, 17, and
      20 weeks. The main outcome measures were infant birth and placental weights,
      length, head, chest, and abdominal circumferences at birth. RESULTS: Placental
      volume in the second trimester was positively associated with all birth
      measurements. Of the fetal measurements at 14 and at 17 weeks, head circumference
      was the strongest predictor of birth weight (B [slope of the regression line]
      =.095, P =.014 at 14 weeks; B =.118, P =.012 at 17 weeks), but at 20 weeks,
      abdominal circumference was the strongest. However, at each age, placental volume
      was the strongest determinant of birth weight, and improved the prediction based
      only on fetal measurements. The odds ratio for low birth weight (under 2500 g)
      increased by 1.68 (95% confidence interval 1.05, 2.69, P = 0.03) for every
      standard deviation decrease in placental volume at 14 weeks' gestation.
      CONCLUSION: The present study suggests that low birth weight was often preceded
      by small placental volume in the second trimester. Placental volume may be a more
      reliable predictor of size at birth than fetal measurements, and may be useful in
      early identification of the fetus at risk in the perinatal period.

PMID- 11506846
TI  - Interleukin-10 inhibition of gelatinases in fetal membranes: therapeutic
      implications in preterm premature rupture of membranes.
AB  - OBJECTIVE: To examine the effect of interleukin-10 on production and regulation
      of gelatinases by amniochorion in an in vitro model of infection. METHODS: We
      placed amniochorionic membranes collected from eight women who had elective
      repeat cesareans at term in an organ explant culture system. After 48 hours in
      culture, the membranes were stimulated with lipopolysaccharide (50 ng/mL), and
      some were costimulated with interleukin-10 (500 ng/mL). Tissue and media samples
      were collected after 24-hour stimulation. Quantitative polymerase chain reactions
      and enzyme-linked immunosorbent assays were used to evaluate matrix
      metalloproteinase 2 and matrix metalloproteinase 9 messenger RNA and proteins,
      respectively. RESULTS: Lipopolysaccharide stimulation induced 55.14 transcripts
      of matrix metalloproteinase 9, compared with 0.83 in control tissues (P <.001).
      Costimulation with interleukin-10 and lipopolysaccharide significantly reduced
      matrix metalloproteinase 9 messenger RNA levels to 10 transcripts (P <.001).
      Lipopolysaccharide stimulation produced 29.25 ng/mL of immunoreactive matrix
      metalloproteinase 9, which was reduced to 6.3 ng/mL (P(adj) =.016) after
      costimulation with interleukin-10. Although not significant, matrix
      metalloproteinase 2 messenger RNA levels were higher in lipopolysaccharide
      stimulated tissues (4.37 x 10(6) transcripts) compared with control (2.8 x 10(5)
      transcripts; P(adj) =.08), with a significant decrease in matrix
      metalloproteinase 2 messenger RNA levels in interleukin-10- costimulated tissues
      (2.9 x 10(6); P(adj) =.007). Interleukin-10 costimulation resulted in a
      significant decrease in matrix metalloproteinase 2 protein production (203.1
      [lipopolysaccharide] and 149.75 [with interleukin-10]; P(adj) <.001). CONCLUSION:
      Interleukin-10 eliminated lipopolysaccharide induction of matrix
      metalloproteinase 2 and 9 in amniochorion.

PMID- 11506847
TI  - Umbilical cord plasma interleukin-6 and fetal growth restriction in preeclampsia:
      a prospective study in Norway.
AB  - OBJECTIVE: To study the association between umbilical plasma levels of
      interleukin-6 (IL-6) in relation to fetal growth in subgroups of preeclampsia,
      and in control pregnancies. METHODS: Umbilical cord plasma was collected from
      12,804 consecutive births. A total of 271 singleton cases of preeclampsia were
      identified, and classified as mild or severe, and as disease with early or late
      onset. As controls, 611 singleton pregnancies without preeclampsia were selected,
      and the ratio between observed and expected birth weight was used as a measure of
      fetal growth. In the analysis, we also included maternal smoking during
      pregnancy. Umbilical cord plasma IL-6 concentration was measured with an IL-6
      bioassay. Comparing controls with subgroups of preeclampsia (severe and early
      onset), this study had a statistical power of 90% to detect a difference in cord
      IL-6 of 10 pg/mL. RESULTS: In severe preeclampsia, cord plasma IL-6 concentration
      was lower than among controls (P <.001), and there was a sharp decrease in cord
      plasma IL-6 with decreasing birth weight ratio (P trend <.001). By further
      dividing the preeclampsia group into early or late onset, the strong association
      between low IL-6 levels and low birth weight ratio appeared to be present mainly
      in early-onset disease. These results were not confounded by maternal smoking.
      CONCLUSION: Restricted fetal growth related to preeclampsia is associated with
      reduced umbilical cord plasma IL-6 concentration in cases with early-onset
      disease. In these cases, fetal growth restriction could be mediated by impaired
      trophoblast function.

PMID- 11506848
TI  - Serum soluble Fas in the syndrome of hemolysis, elevated liver enzymes, and low
      platelets.
AB  - OBJECTIVE: To assess whether serum levels of soluble Fas and soluble Fas ligand
      are altered in the syndrome of hemolysis, elevated liver enzymes, and low
      platelets (HELLP). METHODS: Serum samples from 22 pregnant women diagnosed with
      HELLP syndrome were compared with sera from 37 healthy women with noncomplicated
      singleton pregnancies. Serum levels of soluble Fas and soluble Fas ligands were
      determined by enzyme immunoassay. Student t, chi(2), Pearson's correlation
      coefficient, and multiple regression tests were used for statistical analyses.
      RESULTS: Both soluble Fas and soluble Fas ligand were detected in the sera of
      normal pregnancies as well as in those with HELLP syndrome. The mean serum level
      of soluble Fas was significantly higher in women with HELLP syndrome than in
      healthy gravidas (10.75 +/- 0.93 versus 5.81 +/- 0.37 U/mL, P <.001). However,
      there was no significant difference in mean serum soluble Fas ligand levels of
      the two groups (0.60 +/- 0.06 compared with 0.50 +/- 0.22 ng/mL, P =.23). In
      women with HELLP syndrome, there were no significant correlations between serum
      levels of soluble Fas or soluble Fas ligand with liver transaminases (aspartate
      and alanine aminotransferase) and platelet count. CONCLUSION: Serum levels of
      soluble Fas, but not soluble Fas ligand, are significantly higher in women with
      HELLP syndrome than healthy gravidas. The source of elevated serum levels of
      soluble Fas in HELLP syndrome remains to be determined.

PMID- 11506849
TI  - Relationship among placenta previa, fetal growth restriction, and preterm
      delivery: a population-based study.
AB  - OBJECTIVE: To examine the independent contributions of prematurity and fetal
      growth restriction to low birth weight among women with placenta previa. METHODS:
      A population-based, retrospective cohort study of singleton live births in New
      Jersey (1989-93) was performed. Mother-infant pairs (n = 544,734) were identified
      from linked birth certificate and maternal and infant hospital discharge summary
      data. Women diagnosed with previa were included only if they were delivered by
      cesarean. Fetal growth, defined as gestational age-specific observed-to-expected
      mean birth weight, and preterm delivery (before 37 completed weeks) were examined
      in relation to previa. Severe and moderate categories of fetal smallness and
      large for gestational age were defined as observed-to-expected birth weight
      ratios below 0.75, 0.75-0.85, and over 1.15, respectively, all of which were
      compared with appropriately grown infants (observed-to-expected birth weight
      ratio 0.86-1.15). RESULTS: Placenta previa was recorded in 5.0 per 1000
      pregnancies (n = 2744). After controlling for maternal age, education, parity,
      smoking, alcohol and illicit drug use, adequacy of prenatal care, maternal race,
      as well as obstetric complications, previa was associated with severe (odds ratio
      [OR] 1.37, 95% confidence interval [CI] 1.25, 1.50) and moderate fetal smallness
      (OR 1.24, 95% CI 1.17, 1.32) births. Preterm delivery was also more common among
      women with previa. Adjusted OR of delivery between 20-23 weeks was 1.81 (95% CI
      1.24, 2.63), and 2.90 (95% CI 2.46, 3.42) for delivery between 24-27 weeks. OR
      for delivery by each week between 28 and 36 weeks ranged between 2.7 and 4.0.
      Approximately 12% of preterm delivery and 3.7% of growth restriction were
      attributable to placenta previa. CONCLUSION: The association between low birth
      weight and placenta previa is chiefly due to preterm delivery and to a lesser
      extent with fetal growth restriction. The risk of fetal smallness is increased
      slightly among women with previa, but this association may be of little clinical
      significance.

PMID- 11506850
TI  - Increased erythrocyte adhesiveness and aggregation in peripheral venous blood of
      women with pregnancy-induced hypertension.
AB  - OBJECTIVE: To study the state of erythrocyte adhesiveness/aggregation in the
      peripheral blood of women with pregnancy-induced hypertension as well as in
      matched controls using a simple slide test and image analysis. METHODS: We
      recruited 25 women with pregnancy-induced hypertension. Twenty-five age- and
      gestational age-matched normotensive volunteers took part in the study and served
      as controls. Blood smears were evaluated by an image analysis system (INFLAMET).
      Quantitative measures of erythrocyte aggregation were used to describe the state
      of erythrocyte adhesiveness/aggregation such as vacuum radius, which measures the
      spaces between the aggregated erythrocytes. The number of participants was
      established by power analysis (given alpha of 0.05 and 80% power and considering
      a minimum difference to detect 4 microm in vacuum radius with a standard
      deviation of approximately 5). RESULTS: A significant (P =.002) increment in the
      state of erythrocyte aggregation was noted in the study group compared with the
      controls, the vacuum radius values being 16.1 +/- 1.3 and 10.3 +/- 1.2,
      respectively. Erythrocyte sedimentation rate but not fibrinogen concentration was
      significantly elevated in the study group. The increased aggregation correlated
      significantly with fibrinogen concentration, systolic, and diastolic blood
      pressures. CONCLUSION: We observed increased aggregability of red blood cells in
      hypertensive conditions of pregnancy. Our findings are significant in that they
      reveal blood pressure-related increment in red cell adhesiveness/aggregation
      despite there being no significant increment in clottable fibrinogen
      concentrations.

PMID- 11506851
TI  - Skin flux during reactive hyperemia and local hyperthermia in patients with
      preeclampsia.
AB  - OBJECTIVE: To test the contribution of the endothelium to the maximum
      vasodilatation in patients with preeclampsia and healthy pregnant controls.
      METHODS: Laser-Doppler flowmetry, which is a noninvasive method for the
      continuous measurement of skin blood flow, was used to test the response of skin
      microcirculation to the above-mentioned stimuli in 14 patients with preeclampsia
      and 20 normotensive pregnant controls. RESULTS: In normotensive pregnant
      controls, the reactive hyperemic response after a 3-minute ischemia in the
      forearm reaches values of 77 +/- 16% of the maximum vasodilatation, which was
      induced by local hyperthermia of 42C. In patients with preeclampsia, this
      response was significantly (P <.05) reduced (43 +/- 9%). CONCLUSION: Vascular
      reactivity is altered in skin vessels of patients with preeclampsia in vivo. This
      alteration seems to be attributable mainly to the endothelium.

PMID- 11506852
TI  - Physiologic concentrations of magnesium and placental apoptosis: prevention by
      antioxidants.
AB  - OBJECTIVE: To identify the role of physiologic magnesium concentrations on the
      induction of placental apoptosis in vitro and test the anti-apoptotic action of
      antioxidants. METHODS: Placental tissue was obtained from normal pregnancies
      after cesarean delivery. Placental explants were incubated with increasing
      concentrations of extracellular magnesium (range 0-2.0 mM). Placental apoptosis
      was evaluated by tissue morphology, DNA fragmentation, cytokeratin-18 neoepitope
      formation, and cleavage of plasminogen activator inhibitor type 2. RESULTS:
      Physiologic concentrations of extracellular magnesium stimulated placental
      apoptosis. Magnesium stimulated apoptosis within the physiologic range (0.8-1.2
      mM) (n = 6, P <.001) and was associated with cleavage of plasminogen activator
      inhibitor type 2 and cytokeratin-18 neoepitope formation. These data implicate
      caspase activation in the transduction of the magnesium-induced apoptotic signal.
      Therapeutic concentrations of vitamin C, vitamin E, and acetylcysteine (all at 25
      microg/mL) inhibited DNA fragmentation and attenuated cleavage of plasminogen
      activator inhibitor type 2 and cytokeratin-18 neoepitope formation. CONCLUSION:
      Magnesium-induced placental apoptosis is a potent mechanism of placental
      degeneration in vitro and may represent an important regulator of placental
      tissue dynamics in vivo. The ability of antioxidants to prevent magnesium-induced
      placental apoptosis implicates oxidation-reduction-dependent signaling events in
      this process. Furthermore, these findings provide a basis for further studies of
      antioxidants in mitigating the adverse effects of preeclampsia.

PMID- 11506854
TI  - Retinoic acid and interferon-alpha effects on cell growth and differentiation in
      cervical carcinoma cell lines.
AB  - OBJECTIVE: To investigate and compare the efficacy of all-trans retinoic acid
      (RA) and/or interferon-alpha (IFN-alpha) on premalignant and malignant models of
      cervical cancer. METHODS: Cell growth rate was examined after treatment for 4, 7,
      and 10 days with RA and/or IFN-alpha of human papillomavirus type 18 (HPV 18)
      immortalized endo- and ectocervical cells, nontransformed serum-adapted cells,
      transformed cells, three adenocarcinoma, and three squamous cell carcinoma cell
      lines. The effect on epithelial differentiation by RA and IFN-alpha was examined
      in organotypic culture. Induction of apoptosis was examined by modified terminal
      transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling (TUNEL)
      and DNA fragmentation. RESULTS: Cell growth rate was inhibited by RA, 84-96% in
      HPV 18-immortalized endocervical cells, SiHa, and ME180, 0% in OMC-4, and 18-62%
      in other cell lines; and by IFN-alpha about 75% in SiHa and ME180 and 14-40% in
      the other cell lines. Combining RA and IFN-alpha increased the antiproliferative
      effect in premalignant cell lines and some cancer cell lines except OMC-4, SiHa,
      and HT-3. In rafts, RA treatment reversed human endocervical cell metaplasia and
      HPV 18-immortalized endo- and ectocervical cell dysplastic epithelial
      differentiation. Interferon-alpha, not RA, treatment of HPV 18-immortalized endo-
      and ectocervical cells induced apoptosis. CONCLUSION: Cell growth inhibition by
      treatment with RA, IFN-alpha, and their combination differentially depends on
      treatment type and time, cell origin, cell line, and oncogenic state. In a
      premalignant model of cervical carcinoma, RA reduces dysplastic differentiation
      and IFN-alpha induces apoptosis. These data confirm that these treatments may be
      effective for preventing or treating premalignant cervical lesions.

PMID- 11506853
TI  - Ultrasound and menstrual history in predicting endometrial hyperplasia in
      polycystic ovary syndrome.
AB  - OBJECTIVE: To assess the role of endometrial thickness on vaginal ultrasound
      assessment and menstrual history in predicting endometrial hyperplasia in women
      with polycystic ovary syndrome (PCOS) who presented with infertility due to
      anovulation. METHODS: This was a prospective study in a university referral-based
      fertility and endocrine clinic. Fifty-six women with PCOS presenting with
      infertility due to anovulation underwent both vaginal ultrasound assessments and
      endometrial biopsies. The main outcome measures were the predictive value of
      sonographic endometrial thickness (primary objective) and the menstrual history
      with other clinical characteristics (secondary objective) for proliferative
      endometrium and endometrial hyperplasia in logistic regression analysis. Their
      predictive value was further examined by receiver operating characteristic curve
      analysis. RESULTS: Thirty-six PCOS patients (64.3%) had proliferative endometrium
      and 20 (35.7%) had endometrial hyperplasia. Five of the latter (25%) had
      cytologic atypia. Endometrial thickness less than 7 mm or intermenstrual interval
      less than 3 months (corresponding to more than four menstrual periods yearly) was
      associated with proliferative endometrium only. The endometrial thickness
      correlated positively with endometrial hyperplasia (P =.018) and, together with
      the average intermenstrual interval, were significant predictors of endometrial
      hyperplasia (P <.001). CONCLUSION: These findings point to the usefulness of
      obtaining a detailed menstrual history in women with PCOS by identifying those at
      increased risk of endometrial hyperplasia and who require an endometrial biopsy.
      The endometrial thickness corroborates this clinical impression and is
      particularly useful when the menstrual history is uncertain. Endometrial
      hyperplasia in this population is effectively excluded when the endometrial
      thickness is less than 7 mm.

PMID- 11506855
TI  - Fruit size as a model for teaching first trimester uterine sizing in bimanual
      examination.
AB  - OBJECTIVE: To examine a commonly used fruit-comparison model for teaching uterine
      sizing by bimanual examination, to compare the sizes of actual fruits with
      published first trimester uterine ultrasound measurements, and to estimate the
      degree of provider agreement with this model. METHODS: Actual fruits (pears,
      juice oranges, navel oranges, and grapefruits) were measured. Published
      ultrasound measurements of first trimester pregnant uteri were compared with the
      fruit measurements. A questionnaire was developed and sent to a community-based
      sample of 300 women's healthcare providers selected from a local medical society
      roster of obstetrician-gynecologists and a local reproductive healthcare provider
      list. RESULTS: One hundred twelve (37%) of 300 questionnaires were returned. Of
      these respondents, 55% were medical doctors, 41% nurse-practitioners, and 4%
      midwives. Overall, 75% of respondents agreed (responded either "Agree" or
      "Strongly agree") that a nonpregnant or 5-week pregnant uterus feels like a
      small, unripe pear. Sixty-one percent agreed that a 6-week pregnant uterus feels
      like a small (juice) orange. Eighty percent agreed that an 8-week pregnant uterus
      feels like a large (navel) orange. Eighty-one percent expressed agreement that a
      12-week pregnant uterus feels like a grapefruit. CONCLUSION: The degree of
      provider agreement with the fruit-based teaching model indicates potential
      utility of the model.

PMID- 11506856
TI  - Female sexual response: the role of drugs in the management of sexual
      dysfunction.
AB  - A large component of women's sexual desire is responsive rather than spontaneous.
      Therefore, women's motivation and ability to find and respond to sexual stimuli
      to experience sexual arousal and subsequent sexual desire is crucial, but
      complex. In ongoing relationships, a woman's motivation appears to be largely
      influenced by her emotional intimacy with her partner and her wish to enhance it.
      Drugs (including androgen replacement therapy) aimed at increasing women's
      spontaneous sexual wanting (less characteristic of women in long-term
      relationships) or their arousability may have a role if other psychologic factors
      affecting arousability are addressed in tandem. A woman's sexual arousal is
      composite and complex, correlating well with how mentally exciting she finds the
      sexual stimulus and its context and poorly with objective genital blood flow
      changes. Drugs aimed at increasing the latter, including phosphodiesterase
      inhibitors, may have a role if there is prior careful enquiry as to whether
      genital engorgement is present but not attended to or is physically absent.
      Psychophysiologic studies to date suggest the former is common in women
      presenting with arousal disorder.

PMID- 11506857
TI  - Steroid hormone influence on brain calbindin-D(28K) in male prepubertal and
      ovariectomized rats.
AB  - Calbindin-D(28K) (CALB), a calcium-binding protein, is thought to buffer
      intracellular calcium levels in neurons playing several important roles during
      central nervous system development such as, protecting against apoptosis
      (programmed cell death), neurodegenerative diseases and influencing sexually
      dimorphic brain structures. While preliminary research indicates that calbindin
      levels are modulated by steroids, there has not yet been a comprehensive study to
      determine the role androgens, androgen metabolites and corticosterone have on
      CALB expression in males and throughout the estrous cycle in rats. The present
      study had two main components utilizing Western analysis: (1) examination of the
      influence of steroid hormones (testosterone, dihydrotestosterone, corticosterone,
      and estradiol) and aromatase and 5alpha-reductase blockers on rat brain CALB
      expression in frontal cortex, MBH-POA, and cerebellum of male rats in experiment
      1; (2) characterization of CALB abundance in frontal cortex, MBH-POA, and
      cerebellum throughout the hormonally induced estrous cycle of rats in experiment
      2. There were no significant alterations in CALB levels by any of the treatments
      in experiment 1 or experiment 2 when frontal cortical tissue was examined. In
      male MBH-POA samples, estradiol treatment significantly increased CALB levels
      compared to oil-injection and aromatase or 5alpha-reductase blockers.
      Additionally, DHT treatment significantly increased CALB levels vs. 5alpha
      reductase blocker values. In female samples, MBH-POA CALB levels increased from
      diestrus through proestrus and estrus to metestrus, where metestrus values were
      significantly higher compared to diestrus levels. In the cerebellum, the only
      significant alteration in CALB levels, in males, was observed in corticosterone
      treated animals where a significant decrease was seen compared to oil injection.
      In females, cerebellum CALB levels increased from diestrus through proestus, with
      a slight decrease at estrus. Thereafter, CALB levels increased during metestrus
      where cerebellar CALB values were significantly higher than diestrus levels.
      These findings suggest that steroid hormones play an important regulatory role in
      CALB expression in the brain (except for the frontal cortex) where it potentially
      influences the development/function and neuroprotective changes of
      neuroanatomical structures.

PMID- 11506858
TI  - Effect of gestational ethanol exposure on the NMDA receptor complex in rat
      forebrain: from gene transcription to cell surface.
AB  - Effects of gestational ethanol exposure on the trafficking of the NMDA receptor
      complex were investigated. Studies focused on three distinct processes in NMDA
      receptor translocation: (1) the level of gene transcription (2) nascent NMDA
      receptor subunits (NR) associated with the endoplasmic reticulum bound chaperone
      protein calnexin and (3) NMDA receptors associated with the cell surface
      anchoring protein PSD-95. Forebrain mRNA and membrane proteins were isolated from
      postnatal day 1 rat pups from prenatally ethanol exposed, pair-fed and ad libitum
      experimental groups. Ribonuclease protection assays were carried out to determine
      the levels of NR2A, NR2B, and NR2C mRNA within the treatment groups determined.
      Results indicated that gestational ethanol exposure did not affect the gene
      transcription of the NR2 subunits. Immunoprecipitation experiments were conducted
      with an anti-calnexin antibody or an anti-PSD-95 antibody and the
      immunoprecipitates probed for NR1 and NR2 subunits. Within the anti-calnexin
      immunoprecipitates, no NR2A, NR2B or NR2C subunits were detectable, but a
      significant pool of NR1 subunits was identified. These findings suggest that NR1
      subunits but not NR2 subunits are associated with calnexin within the endoplasmic
      reticulum. Further, gestational ethanol exposure significantly increased the NR1
      polypeptide levels in the anti-calnexin immunoprecipitate. Anti-PSD-95
      immunoprecipitates revealed an abundance of NR1 and NR2B subunits, and these
      complexes were unaffected by gestational ethanol exposure. No NR2A or NR2C
      subunits were detected. These results suggest that gestational ethanol exposure
      significantly affects the assembly and transport of NMDA receptors. Gestational
      ethanol exposure may not alter the composition of the PSD-95 associated NMDA
      receptor complex.

PMID- 11506859
TI  - Spatiotemporal maturation of the central and lateral N1 components to tones.
AB  - This paper examines maturational changes in the spatiotemporal features of
      central and lateral N1 components of the auditory evoked potentials (AEPs) to
      tone stimuli presented with a long stimulus onset asyncrony (SOA; 4200 ms) using
      the scalp current density (SCD) technique. A group of typically developing
      children ranging from 6 to 12 years of age and a group of adults were studied.
      Recently studies have begun to explore the topography of these components in
      children. These studies, however, often used rapidly presented stimuli and did
      not elicit observable central N1s in the younger children. Our stimuli elicited
      both central and lateral N1s. Peak latencies of both components decreased with
      age. Peak amplitude also decreased with age for the lateral N1 but not for the
      central N1. Consequently, the difference between the lateral N1 and the central
      N1 amplitudes (or the ratio of lateral N1 amplitude to central N1 amplitude) also
      decreased with age, dramatically altering the morphology of the elicited AEP
      waveforms. Topography of the lateral N1 did not change with age. The location of
      maximal activation for the central N1 appeared to move more medially with age but
      this 'apparent' movement is probably due to the decreasing impact of the
      partially overlapping lateral N1 component whose amplitude is significantly
      smaller in adults than in children.

PMID- 11506860
TI  - RhoB expression is induced after the transient upregulation of RhoA and Cdc42
      during neuronal differentiation and influenced by culture substratum and
      microtubule integrity.
AB  - RhoGTPases are important intracellular signalling switches in the regulation of
      cytoskeleton organization. They likely have an important role in ontogenesis
      because cytoskeletal rearrangements accompany cell differentiation and
      specialization. Western blotting showed that protein expression of RhoA, RhoB and
      Cdc42 RhoGTPases dramatically increased, in a programmed manner, during neuronal
      differentiation of P19 mouse embryonal carcinoma cells with retinoic acid. RhoA
      and Cdc42 expression were sequentially upregulated and peaked during the
      commitment period while that of RhoB was induced in post-mitotic neurons.
      Although RhoB had a higher expression on matrices allowing cell spreading and
      neurite elongation, it was distributed throughout cell volume by
      immunocytofluorescence and associated with various cell compartments by
      centrifugal subfractionation, suggesting a role not restricted at neurites at
      this stage of differentiation. RhoA and Cdc42 were mainly cytosolic and RhoB
      particulate in the P19 cell model. Treatment of cells with cytoskeleton
      disruptors showed that poisons of microtubules but not of actin filaments or
      neurofilaments increased the cytosolic level of RhoB. The results indicate that
      RhoA, Cdc42 and RhoB must intervene at specific stages of neuronal development
      and there exists a relationship between RhoB expression/distribution, the
      microtubule network and the extracellular matrix during this process.

PMID- 11506861
TI  - Buffering intracellular calcium disrupts motoneuron development in intact
      zebrafish embryos.
AB  - Numerous studies, performed mainly on dissociated cells, have shown that calcium
      signals have a role during different stages of neuronal development. However, the
      actions of calcium during neuronal development in vivo remain to be established.
      The present study has investigated the role of intracellular calcium signals
      during development of motoneurons in the spinal cord of intact zebrafish embryos.
      Loading blastomeres of early embryos with either the calcium buffer BAPTA or the
      calcium reporter dye Calcium Green, was shown to disrupt motoneuron development
      in the spinal cord of embryos at 24 h postfertilisation. Loading the calcium
      buffer BAPTA, at an intracellular concentration of 1 mM, into the blastomeres of
      early embryos did not alter the resting levels of intracellular calcium, but
      significantly dampened transient rises in intracellular calcium in the cells of
      later stage embryos. Loading cells with 1 mM BAPTA significantly decreased the
      number of motoneurons present in the spinal cord at 24 h, indicating that calcium
      signals are important for normal motoneuron differentiation. Furthermore, in
      those BAPTA-filled cells that did adopt a motoneuron cell fate, axogenesis was
      found to be inhibited, suggestive of a role for calcium signalling in neurite
      initiation. This work provides evidence that calcium signals are necessary at
      several stages of motoneuron development in vivo.

PMID- 11506862
TI  - A persistent deficit of serotonin neurons in the offspring of ethanol-fed dams:
      protective effects of maternal ipsapirone treatment.
AB  - An earlier study from this laboratory found a significant reduction in the
      density of serotonin (5-HT) neurons in the dorsal and median raphe and in the B9
      complex of postnatal day 5 (PN5) offspring of female rats that consumed ethanol
      on a chronic basis prior to parturition. In addition, we demonstrated that
      maternal treatment with the 5-HT(1A) agonist ipsapirone (3 mg/kg) prevented the
      ethanol-associated reduction in 5-HT neurons. The present investigation examined
      whether there was a persistent deficit of 5-HT-immunopositive neurons in the
      dorsal and median raphe of the offspring of ethanol-fed dams. We also evaluated
      whether a lower ipsapirone dose (1 mg/kg) was protective to developing 5-HT
      neurons in the offspring of ethanol-fed dams. The offspring of ethanol-fed dams
      exhibited an apparent lasting reduction in the density of 5-HT neurons in the
      dorsal and median raphe. The density of 5-HT neurons in control offspring was
      comparable at PN5 and PN19, but at both ages the offspring of ethanol-fed dams
      had a significant deficit of 5-HT neurons in the dorsal and median raphe. The
      lack of recovery in the density of 5-HT-immunopositive neurons in the offspring
      of ethanol-fed dams between PN5 and PN19 suggests and that the reduction was long
      lasting. The protective effects of ipsapirone appeared to be dose dependent. The
      density of 5-HT neurons in the dorsal and median raphe of PN5 (prior study) and
      PN19 offspring of ethanol-fed dams that were treated with 3 mg/kg of ipsapirone
      between gestational day 13 (G13) and G20 was comparable to that of control
      offspring. However, the effects of maternal treatment of ethanol-fed dams with
      the 1 mg/kg dose were variable, and some abnormalities were detected in the
      offspring of ipsapirone-treated control dams.

PMID- 11506863
TI  - Prenatal exposure to ethinylestradiol elicits behavioral abnormalities in the
      rat.
AB  - Pregnant rats were i.p. injected with a solution of 17alpha-ethinylestradiol (15
      microg kg(-1)) every day between day 9 and day 14 of pregnancy and the behavior
      of the offspring was compared to that of rats born from dams injected with the
      vehicle only during the same gestational period. The percentage of neonatal death
      was dramatically high in the prenatally treated group. Growth of the surviving
      animals was even better than that of controls, but when adult, they exhibited a
      number of behavioral abnormalities: increased spontaneous motor activity,
      decreased exploratory behavior, impaired cognitive processing, qualitatively
      different exploratory drive, and/or persevering behavior, increased anxiety-like
      behavior and social neophobia. These behavioral alterations, which resemble a
      number of psychiatric syndromes, suggest that ethinylestradiol altered the
      ontogenesis of different parts of the central nervous system involved in
      cognitive and emotional processes. However, it cannot be excluded that the
      changes in behavior of ethinylestradiol exposed offspring were due to the
      abnormal maternal behavior of the estradiol treated dams.

PMID- 11506864
TI  - Ectopic expression of tyrosine hydroxylase in Zebrin II immunoreactive Purkinje
      cells in the cerebellum of the ataxic mutant mouse, pogo.
AB  - The pogo mouse is a new ataxic autosomal recessive mutant that arose in an inbred
      strain (KJR/MsKist) derived from a Korean wild mouse. The phenotype includes
      difficulty in maintaining normal posture and the inability to walk straight.
      Several previous studies have associated inherited ataxia with the ectopic
      expression of tyrosine hydroxylase (TH) in Purkinje cells. Therefore, in the
      present study, the distribution of TH expression was compared with that of zebrin
      II in Purkinje cells of adult pogo/pogo mutant mice. In normal control
      littermates, tyrosine hydroxylase immunoreactivity is confined to a delicate
      axonal plexus ramifying through the molecular layer. In pogo/pogo, in addition to
      the axonal plexus, TH-immunoreactive Purkinje cells were present in all lobules
      of the cerebellar vermis and hemispheres, distributed as series parasagittal
      bands. The general pattern of expression is reproducible between individuals and
      symmetrical about the midline. Alternating stripes of TH expression are also seen
      in the hemispheres, and most Purkinje cells in the paraflocculi and flocculi are
      immunoreactive. In pogo/+ mice, TH-immunoreactive Purkinje cells are rare. The
      pattern of zebrin II expression was used to map TH immunoreactive Purkinje cells
      in pogo/pogo mutant mice. Double immunofluorescence labeling combining anti
      zebrin II fand anti-TH showed that all TH-immunoreactive Purkinje cells are
      zebrin II+, but that many zebrin II+ Purkinje cells within a band do not stain
      with anti-TH. Taken together with the morphological changes observed in the
      Purkinje cell axons, this suggests that abnormal Purkinje cell function may
      contribute to the ataxic phenotype in pogo/pogo mice.

PMID- 11506865
TI  - Norepinephrine is required for the anticonvulsant effect of the ketogenic diet.
AB  - Ketogenic diet (KD) is a high fat, low carbohydrate diet used to treat children
      with epilepsy that are refractory to conventional antiepileptic drugs (AEDs). The
      anticonvulsant mechanism of the KD is unknown. To determine if the noradrenergic
      system has a role in mediating the anticonvulsant action of the KD, dopamine beta
      hydroxylase knockout (Dbh -/-) mice that lack norepinephrine (NE) and Dbh +/-
      littermates that have normal NE content were fed either a standard rodent chow or
      the KD. When exposed to the convulsant flurothyl, Dbh +/- mice fed the KD had
      significantly longer latencies to myoclonic jerk (MJ) and generalized clonic
      tonic (CT) seizures than Dbh +/- mice fed normal chow. In contrast, Dbh -/- mice
      fed the KD had seizure latencies to both MJ and CT comparable to Dbh -/- mice fed
      normal chow. These results suggest that an intact, functional noradrenergic
      nervous system is required for the KD to exert an anticonvulsant effect.

PMID- 11506866
TI  - LIS1: from cortical malformation to essential protein of cellular dynamics.
AB  - The LIS1 gene was cloned following the study of children with lissencephaly and
      cytogenetic abnormalities involving chromosome 17p, however, the role of the LIS1
      protein in normal cortical development is not precisely defined. LIS1 is a
      component of evolutionarily conserved intracellular multiprotein complexes and
      recent literature shows that these complexes are essential, not only for neuronal
      migration, but they might also be fundamental components of the machinery for
      cell proliferation and intracellular transport.

PMID- 11506867
TI  - Notch and the birth of glial cells.
AB  - Notch receptors play crucial roles in many cellular differentiation programs. In
      addition to a more classical role for Notch in keeping cells in an
      undifferentiated state, a recent paper has provided clear evidence that Notch
      signaling is a powerful means of turning adult CNS precursor cells into
      astrocytes. This work, combined with other reports from the developing CNS,
      retina and the PNS, demonstrates a role for Notch in gliogenesis. These findings
      can also be linked to novel insights into the function of proneural basic helix
      loop-helix proteins in astrocytic differentiation.

PMID- 11506868
TI  - Can galanin also be considered as growth-associated protein 3.2?
AB  - A recent study has shown that mice containing a loss-of-function mutation in the
      gene encoding galanin exhibit decreased peripheral nerve regeneration after a
      lesion. This major advance indicates, for the first time, that the large
      increases in galanin expression that occur in axotomized peripheral neurons have
      functional consequences for regeneration. Hopefully, similar functional
      consequences will soon be found for other peptides induced in these neurons after
      axotomy, such as vasoactive intestinal peptide and pituitary adenylate cyclase
      activating peptide.

PMID- 11506870
TI  - Viewing odors in the mushroom body of the fly.
AB  - Central processing of olfactory information has been analyzed in the mushroom
      body of Drosophila by Ca(2+) imaging, extending such analysis of odor coding to
      the second relay of the olfactory system. Different odors, and different
      concentrations of a particular odor, yield distinct spatial patterns of activity.
      Mutations that affect odor receptors and odorant-binding proteins affect these
      spatial patterns.

PMID- 11506872
TI  - Heterosynaptic strengthening of hippocampal LTP.

PMID- 11506871
TI  - To be or not to be: a question of B-Raf?
AB  - A recent study has identified the B-Raf gene as essential for the survival of
      explanted sensory and motor neurons in culture in response to neurotrophic
      factors. This finding sheds new light on the control of neuronal development and
      poses new questions with regard to Raf-isozyme-specific functions.

PMID- 11506873
TI  - Learning from flies.

PMID- 11506881
TI  - Developmental dyslexia: the cerebellar deficit hypothesis.
AB  - Surprisingly, the problems faced by many dyslexic children are by no means
      confined to reading and spelling. There appears to be a general impairment in the
      ability to perform skills automatically, an ability thought to be dependent upon
      the cerebellum. Specific behavioural and neuroimaging tests reviewed here
      indicate that dyslexia is indeed associated with cerebellar impairment in about
      80% of cases. We propose that disorders of cerebellar development can in fact
      cause the impairments in reading and writing characteristic of dyslexia, a view
      consistent with the recently appreciated role of the cerebellum in language
      related skills. This proposal has implications for early remedial treatment.

PMID- 11506882
TI  - The cerebellum and dyslexia: perpetrator or innocent bystander?

PMID- 11506883
TI  - A neural instantiation of the motor theory of speech perception.

PMID- 11506884
TI  - Dyslexia, development and the cerebellum.

PMID- 11506885
TI  - Kv3 channels: voltage-gated K+ channels designed for high-frequency repetitive
      firing.
AB  - Analysis of the Kv3 subfamily of K(+) channel subunits has lead to the discovery
      of a new class of neuronal voltage-gated K(+) channels characterized by
      positively shifted voltage dependencies and very fast deactivation rates. These
      properties are adaptations that allow these channels to produce currents that can
      specifically enable fast repolarization of action potentials without compromising
      spike initiation or height. The short spike duration and the rapid deactivation
      of the Kv3 currents after spike repolarization maximize the quick recovery of
      resting conditions after an action potential. Several neurons in the mammalian
      CNS have incorporated into their repertoire of voltage-dependent conductances a
      relatively large number of Kv3 channels to enable repetitive firing at high
      frequencies - an ability that crucially depends on the special properties of Kv3
      channels and their impact on excitability.

PMID- 11506886
TI  - Genetic animal models: focus on schizophrenia.
AB  - The neurobiology of schizophrenia remains poorly understood. Symptoms of
      schizophrenia are classically thought to be associated with an imbalance of the
      dopaminergic system. However, the contribution of other neurotransmitters, in
      particular glutamate, has been increasingly appreciated. The role of individual
      components of neurotransmitter systems in aberrant behaviors can be
      experimentally tested in transgenic animals. Dopamine transporter knockout mice
      display persistently elevated dopaminergic tone and therefore might be
      appropriate substrates to evaluate the dopamine hypothesis. Similarly, NMDA
      receptor-deficient mice can be used to evaluate the glutamate hypothesis of
      schizophrenia. In this review we discuss how such animal models might be relevant
      for understanding the neurochemical underpinnings of certain manifestations of
      schizophrenia.

PMID- 11506887
TI  - Recombinant proteins for neurodegenerative diseases: the delivery issue.
AB  - Tackling neurodegenerative diseases represents a formidable challenge for our
      ageing society. Recently, major achievements have been made in understanding the
      molecular mechanisms responsible for such diseases, and, simultaneously, numerous
      proteins such as neurotrophic factors, anti-apoptotic or anti-oxidant have been
      identified as potential therapeutic agents. Although many neurotrophic factors
      have been tested on individuals suffering from various neurodegenerative
      disorders, to date none has shown efficacy. Inadequate protein delivery is
      believed to be part of the problem. Recent improvements in pump technology, as
      well as in cell and gene therapy, are providing innovative ways to allow
      localized, regulatable delivery of proteins in brain parenchyma, opening new
      avenues for clinical trials in the not so distant future.

PMID- 11506888
TI  - Memory consolidation of Pavlovian fear conditioning: a cellular and molecular
      perspective.
AB  - Pavlovian fear conditioning has emerged as a leading behavioral paradigm for
      studying the neurobiological basis of learning and memory. Although considerable
      progress has been made in understanding the neural substrates of fear
      conditioning at the systems level, until recently little has been learned about
      the underlying cellular and molecular mechanisms. The success of systems-level
      work aimed at defining the neuroanatomical pathways underlying fear conditioning,
      combined with the knowledge accumulated by studies of long-term potentiation
      (LTP), has recently given way to new insights into the cellular and molecular
      mechanisms that underlie acquisition and consolidation of fear memories.
      Collectively, these findings suggest that fear memory consolidation in the
      amygdala shares essential biochemical features with LTP, and hold promise for
      understanding the relationship between memory consolidation and synaptic
      plasticity in the mammalian brain.

PMID- 11506890
TI  - Kinetic studies of Rhizopus oryzae lipase using monomolecular film technique.
AB  - Rhizopus oryzae lipase (ROL) was found to be a true lipase. This enzyme presents
      the interfacial activation phenomenon. The N-terminal amino acid sequence of ROL
      was compared to those of rhizopus lipases. Purified ROL possesses the same N
      terminal sequence as the mature Rhizopus niveus lipase (RNL). This sequence was
      found in the last 28 amino acids of the propeptide sequence derived from the cDNA
      of Rhizopus delemar lipase (RDL). Using the baro-stat method, we have measured
      the hydrolysis rate of dicaprin films by ROL as a function of surface pressure.
      Our results show that Rhizopus oryzae lipase is markedly stereoselective of the
      sn-3 position of the 2,3 enantiomer of dicaprin. Polyclonal antibodies (PAB)
      directed against ROL have been produced and purified by immunoaffinity. The
      effects of these PAB on the interfacial behavior of ROL were determined. The
      immunoblot analysis with polyclonal antibodies anti-ROL (PAB anti-ROL) and
      various lipases shows a cross-immunoreactivity between the lipase from the
      rhizopus family (Rhizopus delemar lipase and Rhizopus arrhizus lipase).

PMID- 11506891
TI  - Pathological alterations induced by neuwiedase, a metalloproteinase isolated from
      Bothrops neuwiedi snake venom.
AB  - The pathological alterations induced by neuwiedase, a 22 kDa class P-I
      metalloproteinase from the venom of the South American pit viper Bothrops
      neuwiedi, were studied in mice. Neuwiedase was devoid of hemorrhagic activity
      when tested in the skin up to a dose of 200 microgram, and also after
      intramuscular injection in the gastrocnemius. However, it induced bleeding when
      applied onto the mouse cremaster muscle in intravital microscopy experiments, and
      caused pulmonary hemorrhage when injected intravenously at doses higher than 5
      microgram/g. Median lethal dose (LD(50)) by the intravenous route was 5
      microgram/g, whereas LD(50) of crude venom was 0.47 microgram/g. After
      intramuscular injection, neuwiedase induced a mild myotoxic effect, evidenced
      histologically and by the increment in plasma creatine kinase activity, but it
      was devoid of hemorrhagic and thrombotic effects. In contrast, crude B. neuwiedi
      venom induced prominent hemorrhage and myonecrosis in gastrocnemius muscle. Both
      venom and neuwiedase induced an inflammatory reaction in muscle tissue
      characterized by abundant polymorphonuclear leukocytes. Moreover, a conspicuous
      edema developed in the foot pad after subcutaneous injection of neuwiedase. Anti
      neuwiedase antibodies produced in rabbits were effective in the neutralization of
      hemorrhagic activity of crude venom, evidencing immunological cross-reactivity
      between neuwiedase and other hemorrhagic metalloproteinases present in the venom,
      and suggesting that metalloproteinases devoid of, or having low, hemorrhagic
      activity could be good immunogens to generate antibodies effective against high
      molecular mass metalloproteinasas having potent hemorrhagic activity. It is
      concluded that neuwiedase, despite its lack of hemorrhagic effect when injected
      in the gastrocnemius muscle, contributes to local tissue damage by inducing
      edema, inflammatory infiltrate and mild myotoxicity, and by degrading
      extracellular matrix components. In addition, large doses of neuwiedase may
      contribute to pulmonary bleeding

PMID- 11506892
TI  - New subtilisin-like collagenase from leaves of common plantain.
AB  - A new subtilisin-like proteinase hydrolyzing chromogenic peptide substrate Glp
      Ala-Ala-Leu-p-nitroanilide optimally at pH 8.1 was found in common plantain
      leaves. The protease named plantagolisin was isolated by ammonium sulfate
      precipitation of the leaves' extract followed by affinity chromatography on
      bacitracin-Sepharose and ion-exchange chromatography on Mono Q in FPLC regime.
      Its molecular mass is 19000 Da and pI 5.0. pH-stability range is 7-10 in the
      presence of 2 mM Ca(2+), temperature optimum is 40 degrees C. The substrate
      specificity of subtilase towards synthetic peptides and insulin B-chain is
      comparable with that of two other subtilisin-like serine proteinases: proteinase
      from leaves of the sunflower and taraxalisin. Besides, the proteinase is able to
      hydrolyze substrates with Pro in P(1) position. The enzyme hydrolyzes collagen.
      alpha and beta chains are hydrolyzed simultaneously in parallel; there are only
      low-molecular-mass hydrolysis products in the sample after 2 h of incubation.
      Pure serine proteinase was inactivated by specific serine proteinases inhibitors:
      diisopropylfluorophosphate, phenylmethylsulfonyl fluoride and Hg(2+). The
      plantagolisin N-terminal sequence ESNSEQETQTESGPGTAFL-, traced for 19 residues,
      revealed 37% homology with that of subtilisin from yeast Schizosaccharomyces
      pombe.

PMID- 11506893
TI  - Ceruloplasmin enhances DNA damage induced by cysteine/iron in vitro.
AB  - Ceruloplasmin (Cp) was found to promote the oxidative damage to DNA in vitro, as
      evidenced by the formation of 8-hydroxy-2'-deoxyguanosine and strand breaks, when
      incubated with a cysteine metal-catalyzed oxidation system (Cys-MCO) comprised of
      Fe(3+), O(2), and cysteine as an electron donor. The capacity of Cp to enhance
      oxidative damage to DNA was inhibited by hydroxyl radical scavengers such as
      sodium azide and mannitol, a metal chelator, diethylenetriaminepentaacetic acid,
      a spin-trapping agent, 5,5-dimethyl-1-pyrroline N-oxide (DMPO) and catalase.
      Ceruloplasmin also caused the two-fold enhancement of a mutation in the pUC18
      lacZ' gene in the presence of Cys-MCO when measured as a loss of alpha
      complementation. Incubation of Cp with Cys-MCO resulted in an increase in the
      content of carbonyl groups and the significant alteration of the ferroxidase
      activity, as well as the proteolytic susceptibility. The deoxyribose assay and
      the salicylate hydroxylation assay showed that hydroxyl free radicals were
      generated in the reaction of Cp with Cys-MCO. The release of a portion of Cu from
      Cp was observed, and conformational alterations were indicated by the changes in
      fluorescence spectra. Based on these results, we interpret the enhancing effect
      of Cp on DNA damage and mutagenicity induced by Cys-MCO as due to reactive oxygen
      species, probably hydroxyl free radicals, formed by the reaction of free Cu(2+),
      released from oxidatively damaged Cp, and H(2)O(2) produced by Cys-MCO. The
      release of Cu from Cp during oxidative stress could enhance the formation of
      reactive oxygen species and could also potentiate cellular damage.

PMID- 11506894
TI  - Structural stabilization displayed in the soluble phase of cocrystallization of
      flavianic acid with trypsin in acid media.
AB  - Coprecipitation and cocrystallization of proteins with synthetic dyes are known
      to involve reversible denaturation processes which can offer specificity towards
      a target protein. Although the knowledge of conformational equilibrium and how to
      control it are central into the basic molecular dynamics of protein
      precipitation, the exact molecular mechanism of the precipitation remains
      unknown. Aiming at understanding the events that take place before the
      coprecipitation step of generic dye-protein systems, we investigated the binding
      of flavianic acid to bovine trypsin, using approaches of visible and second
      derivative ultraviolet spectroscopy, viscosimetry, densimetry and circular
      dichroism. The results suggest a restricted transconformation of the
      macromolecule linked to dye binding at a stoichiometry of 1:1. An increase on the
      protein secondary structures occurred together with an electro-constriction
      effect on trypsin, a borderline event to the coprecipitation process, suggesting
      a stabilized structure for trypsin as a ligand-induced molten globule-like state.

PMID- 11506895
TI  - Depletion and deletion analyses of eucaryotic translation initiation factor 1A in
      Saccharomyces cerevisiae.
AB  - Translation initiation factor eIF1A is a highly conserved, small, acidic protein
      that is required for cell growth in yeast. Biochemical studies in vitro implicate
      eIF1A in dissociating ribosomes, promoting methionyl-tRNA(i) binding to 40S
      ribosomal subunits, scanning of mRNAs and recognizing the AUG initiation codon.
      To elucidate the pleiotropic functions of eIF1A in vivo, the factor was depleted
      by placing its gene behind the repressible GAL1 promoter. After Saccharomyces
      cerevisiae cells were shifted to glucose medium, depletion of eIF1A was seen
      after 3-4 generations, corresponding with cessation of cell growth. Polysome
      profiles of the depleted strain showed ribosome run-off from mRNAs, indicating
      that eIF1A is involved in the initiation phase of translation. A decrease in free
      40S ribosomes and an apparent increase in free 60S ribosomes were attributed to
      the formation of 40S subunit dimers. The result suggests that one of the
      functions of eIF1A is to prevent formation of 40S dimers. Mutant forms of eIF1A
      lacking either the positively charged N-terminal region or the negatively charged
      C-terminal region were constructed and tested for their ability to confer cell
      growth as the sole source of eIF1A. Either deletion supports cell growth, albeit
      at a slower rate, and causes a reduction in polysomes, although eIF1A lacking the
      N-terminal region is more deleterious. Therefore the charged terminal regions
      contribute to, but are not absolutely essential for, eIF1A function.

PMID- 11506896
TI  - Induction of vascular endothelial growth factor by nitric oxide in cultured human
      articular chondrocytes.
AB  - We investigated the role of nitric oxide (NO) in the control of vascular
      endothelial growth factor A (VEGF) gene expression in cultured human articular
      chondrocytes. Cell treatment with the NO-generating compound nitrosoglutathione
      (GSNO) caused a significant accumulation of 4.4 kb VEGF mRNA, a major VEGF mRNA
      isoform expressing in chondrocytes. This is the first demonstration that NO can
      induce VEGF mRNA expression in chondrocytes. VEGF mRNA level was not affected in
      cells exposed to dibutyryl cGMP, a non-hydrolyzable analog of cGMP, suggesting
      that the cGMP system is not involved in NO-dependent transcriptional activation
      of VEGF gene. The GSNO-stimulated induction of VEGF mRNA was slightly attenuated
      by MAP protein kinase inhibitors PD98058 and SB203580, but was completely blocked
      in cells incubated with GSNO in the presence of catalase and superoxide
      dismutase, enzymes scavenging reactive oxygen species (ROS), or in the presence
      of thiol-containing antioxidants, N-acetyl cysteine and reduced glutathione.
      These results suggest that in articular chondrocytes the GSNO-induced VEGF gene
      transcriptional activation is dependent on endogenous ROS production and
      oxidative thiol modifications.

PMID- 11506897
TI  - ADP is produced by firefly luciferase but its synthesis is independent of the
      light emitting properties.
AB  - During experiments aimed at understanding the time course of appearance of
      reaction products in the Photinus pyralis luciferase system, an expected compound
      with a typical nucleotide UV spectrum was isolated. According to capillary
      electrophoresis (CE) analysis and 1H, 31P-NMR spectra, it was unambiguously found
      to be ADP, either with extracted or recombinant enzymes. The ADP synthesis was
      demonstrated by standard UV spectrophotometric methods and CE analysis. Also, the
      luciferase produced AMP and ATP from ADP. This reaction was completely inhibited
      by Ap(5)A at 250 nM and was independent of the light emitting properties of the
      enzyme. The only catalytic mechanism to explain the production of ADP is an
      intrinsic adenylate kinase activity of luciferase. The K(m) values of the AK
      activity are 0.3, 0.7, 0.06 mM for AMP, ADP, and ATP respectively. The multiple
      enzyme activities of luciferase may be partly responsible for the complex
      kinetics of light emission by changing the nucleotide concentrations.

PMID- 11506898
TI  - Identification, quantification and fine structural characterization of
      glycosaminoglycans from uterine leiomyoma and normal myometrium.
AB  - The type, amount and fine chemical composition of glycosaminoglycans (GAGs)
      present both in human normal myometrium and uterine leiomyoma have been studied.
      GAGs were fractionated by ion-exchange chromatography on DEAE-Sephacel, isolated
      by gel-permeation chromatography on Sepharose CL-6B and characterized using
      electrophoresis in cellulose acetate membranes, specific enzymic treatments and
      analysis by high-performance capillary electrophoresis (HPCE). No statistical
      intrabatch differences in total GAG content in both tissues were identified,
      whereas significant interbatch differences between normal myometrium and uterine
      leiomyoma were recorded. Hyaluronan (HA), chondroitin sulphate (CS), dermatan
      sulphate (DS), heparan sulphate (HS) and keratan sulphate (KS) were identified in
      both tissues. Statistically significant (P </= 0.001) differences in uterine
      leiomyoma in the content of HA (-27.7%), DS (+158.5%), KS (+116.4%) and HS (
      52.5%), as compared to normal myometrium, were determined. Despite the
      differences in the amount of GAGs, no significant differences in the fine
      chemical composition of CS and DS were identified. It is worth noting that DS of
      both tissues is constructed by glucuronic acid-containing long repeats separated
      by a few iduronic acid residues. The results of this study suggest that the
      development of uterine leiomyoma is closely related to quantitative changes at
      the GAG level. The increase of DS and KS may well be related to increased
      neosynthesis of fibrotic connective tissue, whereas the decrease of HA and the
      unaltered amounts of CS may also indicate benign tumors of low growth rate.

PMID- 11506899
TI  - alpha1(I) collagen gene expression in quail epiphyseal chondrocytes.
AB  - We examined alpha1(I) collagen expression by using primary cultures of quail
      epiphyseal chondrocytes which exhibit high levels of synthesis of cartilage
      specific collagens and do not undergo phenotypic modulation when replated onto
      collagens I and II or fibronectin. These cells also synthesize proalpha1(I)
      collagen chain, however, alpha1(I) mRNA fails to be detected by Northern blot and
      RNase protection analysis. Nuclear transcription rate with a 5-end specific probe
      is detected in suspension quail chondrocytes and RT-PCR analysis shows the
      presence of low levels of alpha1(I) mRNA in these cells. The lack of
      correspondence between procollagen mRNA levels and the rate of collagen synthesis
      is consistent with previous reports describing the regulation of this transcript
      in chondrocytes and in collagen I-producing cells.

PMID- 11506900
TI  - Triclosan: a widely used biocide and its link to antibiotics.
AB  - Triclosan is the active ingredient in a multitude of health care and consumer
      products with germicidal properties, which have flooded the market in recent
      years in response to the public's fear of communicable bacteria. Although
      originally thought to kill bacteria by attacking multiple cellular targets,
      triclosan was recently shown to target a specific bacterial fatty acid
      biosynthetic enzyme, enoyl-[acyl-carrier protein] reductase, in Gram-negative and
      Gram-positive bacteria, as well as in the Mycobacteria. Triclosan resistance
      mechanisms include target mutations, increased target expression, active efflux
      from the cell, and enzymatic inactivation/degradation. These are the same types
      of mechanisms involved in antibiotic resistance and some of them account for the
      observed cross-resistance with antibiotics in laboratory isolates. Therefore,
      there is a link between triclosan and antibiotics, and the widespread use of
      triclosan-containing antiseptics and disinfectants may indeed aid in development
      of microbial resistance, in particular cross-resistance to antibiotics.

PMID- 11506901
TI  - L-Nucleosides as chemotherapeutic agents.
AB  - Nucleoside analogues have been the cornerstone of antiviral therapy over the past
      thirty years and, currently, 16 commonly used antiviral drugs belong to this
      category. Although for long time it was believed that only D-nucleosides,
      possessing a 'natural' stereochemistry, could elicit biological activity, in the
      last decade this has been proven not to be true. 3TC, a L-nucleoside analogue, is
      one of the most effective anti-HIV and anti-hepatitis B virus drugs, and nine
      other L-nucleosides are currently undergoing clinical trials and/or preclinical
      studies as antiviral or antitumoral agents. This minireview summarizes some
      biological features and the current status of these promising L-nucleoside
      analogues.

PMID- 11506902
TI  - The significance of nasal carriage of Staphylococcus aureus as risk factor for
      human skin infections.
AB  - The present study was designed to investigate the significance and the
      relationship between nasal carriage of Staphylococcus aureus and staphylococcal
      skin infections. Thirty-one S. aureus strains, isolated from 12 patients with
      chronic and recurrent skin infections, one patient with septicemia and one
      patient with otitis externa were studied. The staphylococcal strains were
      isolated from the site of infection and from the anterior nares of each patient.
      The identity of both strains of each pair could be demonstrated by determination
      of phenotypic properties and by genotyping of the isolates. The phenotypic
      properties included hemolytic activities, antibiotic resistance data, and the
      production of enterotoxins. The identity was additionally confirmed by phage
      typing, by determination of the size and the number of repeats of the X region of
      spa gene, by determination of gene polymorphisms of coa gene and by
      macrorestriction analysis of the chromosomal DNA of the isolates by pulsed-field
      gel electrophoresis. The present results showed an identity of the S. aureus
      obtained from anterior nares and from skin infection of each patient indicating
      the importance of nasal carriage of these bacteria for development of human skin
      infection.

PMID- 11506903
TI  - Fimbria-mediated bacterial adhesion to human oral epithelium.
AB  - Oral mucosa biopsies and saliva samples from 12 individuals were processed for
      transmission (TEM) and scanning (SEM) electron microscopy with and without
      ruthenium red staining. Additionally performed microbiological estimations
      indicated in all bacteriological samples a facultative pathogenic flora. SEM and
      TEM investigation showed a diverse bacterial flora attached to the mucosal
      surface. Fimbriae comprising the glycocalyx and enabling bacterial attachment to
      the epithelial cells could be clearly visualised by ruthenium red. The only mode
      of bacterial attachment to the oral mucosa detected in the present investigation
      was fimbria-mediated adhesion and co-adhesion. The fimbria-mediated adhesion
      enables the bacterial persistence in the oral cavity and is the first step in the
      bacterial colonisation process.

PMID- 11506904
TI  - Induction of iNOS in human monocytes infected with different Legionella species.
AB  - The contribution of nitric oxide (NO) radicals to the suppression of
      intracellular replication of Legionella has been well established in rodents but
      remained questionable in humans. Considering the fact that human monocytes do not
      exhibit a high-output NO production, we used sensitive methods such as detection
      of inducible NO synthase (iNOS) mRNA by reverse transcription-PCR and
      demonstration of iNOS protein expression by means of flow cytometry and Western
      blot to compare the levels of iNOS induced by Legionella species which, in
      accordance to their human prevalence, show different multiplication rates within
      human monocytic cells. The expression of iNOS in Mono Mac 6 (MM6) cells showed an
      only moderate inverse correlation to the intracellular replication rate of a
      given Legionella species in the protein expression assays. However, stimulation
      of host cells with 1,25-dihydroxyvitamin D(3) to enhance NO production and
      inhibition of NO production by treatment of host cells with N(G)-methyl-L
      arginine were not able to modify the intracellular multiplication of legionellae
      within MM6 cells. Therefore, NO production does not seem to play a crucial role
      for the restriction of intracellular replication of Legionella bacteria within
      human monocytic cells. Rodent models in investigations which are supposed to
      clarify the involvement of NO radicals in defense mechanisms against Legionella
      infections in humans are of doubtful significance.

PMID- 11506905
TI  - Tolerance to high osmolality of Lactococcus lactis subsp. lactis and cremoris is
      related to the activity of a betaine transport system.
AB  - Lactococcus lactis strains from the subsp. cremoris are described as more
      sensitive to osmotic stress than subsp. lactis strains. We examined the relation
      between osmotic tolerance and the activity of the betaine transporter BusA among
      34 strains of L. lactis. The cremoris strains that showed reduced growth at high
      osmolality failed to accumulate betaine. The nature of the defect was found to
      vary among cremoris strains: lack of the busA encoding region, absence of
      synthesis or synthesis of an inactive form of BusA. The results suggest that the
      selection of strains well fitted to the dairy production lead to the loss of an
      otherwise efficient adaptation mechanism.

PMID- 11506906
TI  - Sequence, cloning, expression and characterisation of the 81-kDa surface membrane
      protein (P80) of Mycoplasma agalactiae.
AB  - Mycoplasma agalactiae, the causative agent of contagious agalactia in small
      ruminants, produces a protein, named P80, that is detectable in all wild-type
      isolates examined to date and that appears expressed during the early phase of
      infection. We describe here the identification, cloning and expression of the
      gene encoding P80 (ma-mp81). The deduced amino acid sequence is consistent with a
      hydrophobic and basic protein that possesses a lipoprotein signal peptide.
      Sequence analysis of gene ma-mp81 suggests that P80 is a membrane lipoprotein
      that shows significant homology with other putative lipoproteins of M.
      pneumoniae. An internal 1-kb fragment of ma-mp81 was expressed in Escherichia
      coli as a 6xHis-tagged protein. The purified recombinant protein greatly reacted
      with polyclonal anti-P80 sera raised in lamb.

PMID- 11506907
TI  - Quantification of the carbazole 1,9a-dioxygenase gene by real-time competitive
      PCR combined with co-extraction of internal standards.
AB  - The fluorogenic probe assay, competitive polymerase chain reaction (PCR) and co
      extraction with internal standard cells were combined to develop a rapid,
      sensitive, and accurate quantification method for the copy number of a target
      carbazole 1,9a-dioxygenase gene (carAa) and the cell number of Pseudomonas sp.
      strain CA10. The internal standard DNA was modified by replacement of a 20-bp
      long region with one for binding a specific probe in fluorogenic PCR (TaqMan).
      The resultant DNA fragment was similar to the corresponding region of the intact
      carAa gene in terms of G+C content. When used as a competitor in the PCR
      reaction, the internal standard DNA was distinguishable from the target carAa
      gene by two specific fluorogenic probes with different fluorescence labels, and
      was automatically detected in a single tube using the ABI7700 sequence detection
      system. To minimize variations in the efficiency of cell lysis and DNA extraction
      between the samples, the co-extraction method was combined. A mini-transposon was
      used to introduce competitor DNA into the genome of other pseudomonads, and the
      resultant construct was used as the standard cell. After the addition of a fixed
      amount of the internal standard cells to soil samples, total DNA was extracted
      (co-extraction). Using this method, the copy number of the carAa gene and the
      cell number of strain CA10 in soil samples could be quantified rapidly.

PMID- 11506908
TI  - Increased levels of sigJ mRNA in late stationary phase cultures of Mycobacterium
      tuberculosis detected by DNA array hybridisation.
AB  - In order to determine which genes are involved in maintaining viability of 100
      day stationary-phase bacteria and persistent bacteria after antibiotic treatment,
      we used a mini-DNA array to examine the transcription of 82 genes of M.
      tuberculosis in the 100-day stationary-phase cultures before and after rifampicin
      treatment. We found that the mRNA level of a sigma factor gene, sigJ, was
      strongly up-regulated in the late stationary-phase cultures. Other genes were
      also up-regulated, although to a lesser extent than sigJ. Surprisingly, after
      rifampicin treatment there was no significant change in sigJ expression, and most
      of the other 82 genes in the mini-DNA array also maintained expression, some at
      relatively high levels. These results suggest that SigJ may control gene
      expression in the quiescent state and may be an important component in the
      mechanisms by which M. tuberculosis survives prolonged stationary phase even in
      the presence of sterilising antibiotics.

PMID- 11506909
TI  - Identification and characterization of a high-affinity zinc uptake system in
      Neisseria gonorrhoeae.
AB  - A search of the gonococcal genome database using the known zinc-binding protein
      (znuA) sequences from Escherichia coli and Haemophilus influenzae identified an
      open reading frame encoding a putative gonococcal ZnuA. The consensus amino acid
      sequence of this open reading frame possessed a characteristic 30-amino acid
      histidine-rich metal-binding motif (repetitive HDH sequence) containing 43%
      histidine and 37% aspartic acid and glutamic acid. Subsequently, two adjacent
      open reading frames with homology to E. coli and H. influenzae znuB and znuC were
      located upstream of znuA. When partially purified from sonicated cell-free
      supernatants by CM-Sepharose chromatography, the mature gonococcal ZnuA had an
      estimated molecular mass of 38 kDa by SDS-PAGE. The presence of a DNA sequence
      encoding a 19-amino acid signal peptide and the solubility of the mature ZnuA
      suggested that this protein was located in the periplasm. Inactivation of the
      Neisseria gonorrhoeae F62 znuA by insertional mutagenesis resulted in a mutant
      that had a growth rate lower than that of the wild-type parent strain and that
      required high concentrations of ZnCl2 (> or = 200 microM) for optimal growth.
      Using a chemically defined agar medium, the gonococcal ZnuA mutant grew only in
      the presence of Zn(2+), whereas Mg(2+), Ca(2+), Ni(2+), Fe(2+), Cu(2+), Mn(2+)
      and Cd(2+) had either no effect or were growth inhibitory.

PMID- 11506910
TI  - Differential expression of proteolytic enzymes in endosymbiont-harboring
      Crithidia species.
AB  - Crithidia oncopelti, Crithidia deanei and Crithidia desouzai are flagellates of
      the Trypanosomatidae family that present bacterium-like endosymbionts in their
      cytoplasm. Gelatin-SDS-PAGE analysis was used to characterize cell-associated and
      extracellular proteinases in these organisms. Our survey indicates that the
      proteolytic profiles of C. deanei and C. desouzai are identical; that C.
      oncopelti displays a distinct zymogram; and that species naturally lacking
      endosymbionts have a more complex extracellular proteolytic activity, which
      illustrates the heterogeneity of this genus. This is the first report on the
      presence of cysteine proteinases in the culture supernatant of monoxenic
      trypanosomatids, and by the use of wild and aposymbiotic strains from C. deanei
      we also demonstrated that the prokaryote endosymbiont somehow alters
      quantitatively the expression of extracellular proteinases in this
      trypanosomatid.

PMID- 11506911
TI  - Presence of high-affinity iron uptake systems in fish-isolated and environmental
      strains of Vibrio anguillarum serotype O3.
AB  - This work describes the presence of high-affinity iron uptake systems in Vibrio
      anguillarum serotype O3 strains (subgroups A and B), isolated from diseased fish
      and environmental samples, as well as the presumptive effect of iron on their
      virulence. All strains demonstrated an ability to grow under iron-limiting
      conditions, production of catechol-type siderophores and synthesis of iron
      regulated outer membrane proteins. However, clear differences were found
      depending on the isolation source, suggesting a more efficient iron uptake system
      in fish-isolated strains. Comparing the iron-regulated outer membrane protein
      profiles with those described for O1 and O2 serotypes, we found a protein which
      is specific for serotype O3, and another one that allows the differentiation of
      serotype O3 fish isolates from environmental strains. Moreover, only the strains
      showing this protein increased their virulence when iron was added to the
      inoculum in pathogenicity assays.

PMID- 11506912
TI  - Cloning, expression and characterisation of a Family B ATP-dependent
      phosphofructokinase activity from the hyperthermophilic crenarachaeon Aeropyrum
      pernix.
AB  - We have cloned a Family B sugar kinase gene from the aerobic hyperthermophilic
      crenarchaeon Aeropyrum pernix and have subsequently expressed the protein in
      Escherichia coli. The enzyme was purified with its associated histidine-tag by
      affinity chromatography with a nickel-nitrilotriacetic acid column followed by
      cation exchange chromatography and possesses a high degree of thermostable ATP
      dependent phosphofructokinase activity. The enzyme has an estimated apparent K(m)
      for ATP and fructose-6-phosphate of 0.027 and 1.212 mM, respectively, that were
      determined in discontinuous assays at 95 degrees C. The Family B ATP-dependent
      phosphofructokinase has a half-life of approximately 30 min at 95 degrees C and
      is indicated to be monomeric. The implications of the presence of a Family B
      phosphofructokinase in the Crenarchaea are discussed with reference to the
      origins of the Embden-Meyerhof pathway.

PMID- 11506913
TI  - Molecular diversity of live-attenuated prototypic vaccine strains and clinical
      isolates of Staphylococcus aureus.
AB  - Bovine mastitis Staphylococcus aureus isolates and prototypic live-attenuated
      vaccine strains were analyzed by SmaI pulsed-field gel electrophoresis (PFGE)
      typing and automated ribotyping. The discriminatory index of these methods was
      0.91 and 0.69, respectively. SmaI PFGE typing assigned all laboratory strains
      into cluster Q, which shared 49% similarity with clusters A and B, and 35%
      similarity with cluster C. Automated ribotyping placed laboratory strains within
      ribogroups different from those of bovine isolates. These methods have 70%
      concordance and permitted identification of the prototypic vaccine background
      from those of clinical isolates. This information is required before conducting
      field trials with the vaccine.

PMID- 11506914
TI  - Phylogenetic diversity of thermophilic actinomycetes and Thermoactinomyces spp.
      isolated from mushroom composts in Korea based on 16S rRNA gene sequence
      analysis.
AB  - Forty one strains isolated from 21 samples of various mushroom composts in Korea
      were analyzed by 16S rRNA gene sequencing to investigate the phylogenetic
      diversity of thermophilic actinomycetes. The 25 strains of thermophilic
      actinomycete isolates were related to the five genera, Pseudonocardia,
      Saccharomonospora, Saccharopolyspora, Streptomyces, and Thermobifida, within the
      order Actinomycetales, and 16 strains were classified into the genus
      Thermoactinomyces within the family Bacillaceae. Most of 41 isolates were
      encompassed by two genera, Streptomyces and Thermoactinomyces, that were isolated
      mainly in composts prepared from waste cotton and hay, respectively. Among them,
      M104 and M109 were placed in distinct taxonomic positions although these strains
      formed phylogenetic lineages related to the genus Streptomyces and to the family
      Streptosporangiaceae, respectively. Therefore, a phenetic and genetic
      characterization of these strains will be needed to pinpoint their taxonomic
      position.

PMID- 11506915
TI  - A catalase gene of Colletotrichum gloeosporioides f. sp. malvae is highly
      expressed during the necrotrophic phase of infection of round-leaved mallow,
      Malva pusilla.
AB  - A small-subunit peroxisomal catalase gene, cgcat1, was cloned from Colletotrichum
      gloeosporioides f. sp. malvae, a hemibiotrophic pathogen of round-leaved mallow
      (Malva pusilla). When compared to the expression of an actin gene of the fungus,
      a much lower level of expression of cgcat1 was detected in the biotrophic phase
      than in the subsequent necrotrophic phase of infection. In culture, cgcat1was
      expressed at higher levels when exposed to hydrogen peroxide. Changes in cgcat1
      expression during infection may have related to an attempt to prevent damage from
      hydrogen peroxide from degenerating host cells, and/or resulted from changes in
      fungal nutrition and development during invasion of the host.

PMID- 11506916
TI  - Intraspecific diversity of Oenococcus oeni isolated during red wine-making in
      Japan.
AB  - Using molecular and chemotaxonomic techniques, we studied the intraspecific
      diversity of Oenococcus oeni, a lactic acid bacterium isolated during red wine
      making in Japan. The results confirmed high values of DNA-DNA relatedness and
      strong similarity among 16S rDNA sequences of the isolates with the O. oeni-type
      strain. Pulsed-field gel electrophoresis (PFGE) by NotI identified four patterns
      among the strains. Three different patterns of lactate dehydrogenase mobility
      were seen and there was a strong correlation between PFGE pattern and mobility.
      The present results suggest that the different strains of O. oeni comprise one
      species, and that variations in the genomic profiles of the different strains of
      O. oeni, including Japanese isolates are well correlated.

PMID- 11506917
TI  - Expression and characterization of the terminal heme synthetic enzymes from the
      hyperthermophile Aquifex aeolicus.
AB  - The terminal two heme biosynthetic pathway enzymes, protoporphyrinogen oxidase
      and ferrochelatase, of the hyperthermophilic bacterium Aquifex aeolicus have been
      expressed in Escherichia coli, purified to homogeneity, and biochemically
      characterized. Ferrochelatase and protoporphyrinogen oxidase of this organism are
      both monomeric, as was found for the corresponding enzymes of Bacillus subtilis.
      However, unlike the B. subtilis proteins, both A. aeolicus enzymes are membrane
      associated. Both proteins have temperature optima over 60 degrees C. This is the
      first demonstration of functional heme biosynthetic enzymes in an extreme
      thermophilic bacterium.

PMID- 11506918
TI  - H2 consumption by Escherichia coli coupled via hydrogenase 1 or hydrogenase 2 to
      different terminal electron acceptors.
AB  - Hydrogen uptake in the presence of various terminal electron acceptors was
      examined in Escherichia coli mutants synthesizing either hydrogenase 1 or
      hydrogenase 2. Both hydrogenases mediated nitrate-dependent H2 consumption but
      neither of them was coupled with nitrite. Unlike hydrogenase 2, hydrogenase 1
      demonstrated poor activity with electron acceptors of low midpoint redox
      potential. Oxygen-linked H2 uptake via hydrogenase 1 was observed over a wide
      range of air concentrations. Hydrogenase 2 catalyzed this reaction only at low
      air concentrations. Thus, hydrogenase 1 works in cells at higher redox potential,
      being more tolerant to oxygen than hydrogenase 2.

PMID- 11506919
TI  - Age-dependent presence of antibodies in rat dams, capable of conferring
      protection against group B Streptococcus infection in neonates.
AB  - A rat model was used to investigate maternal age-dependent resistance on group B
      Streptococcus (GBS)-induced mortality of the offspring. Offspring from young
      (first time) or older (repeat litters) dams were challenged with GBS. There was
      an approximate log difference in the dose of GBS required to cause identical
      levels of mortality in the two groups. The sera of the dams from both groups were
      analysed by whole-cell ELISA, and it was demonstrated that sera from the older
      dams possessed circulating IgG cross-reactive to GBS. Since IgG is
      transplacentally transferred, we conclude that this is the method of observed
      protection.

PMID- 11506920
TI  - Production in vitro, on different solid culture media, of two distinct
      exopolysaccharides by a mucoid clinical strain of Burkholderia cepacia.
AB  - The production of exopolysaccharides (EPSs) by a mucoid clinical isolate of
      Burkholderia cepacia involved in infections in cystic fibrosis patients, was
      studied. Depending on the growth conditions, this strain was able to produce two
      different EPS, namely PS-I and PS-II, either alone or together. PS-I is composed
      of equimolar amounts of glucose and galactose with pyruvate as substituent, and
      was produced on all media tested. PS-II is constituted of rhamnose, mannose,
      galactose, glucose and glucuronic acid in the ratio 1:1:3:1:1, with acetate as
      substituent, and was produced on either complex or minimal media with high-salt
      concentrations (0.3 or 0.5 M NaCl). Although this behavior is strain-specific,
      and not cepacia-specific, the stimulation of production of PS-II in conditions
      that mimic those encountered by B. cepacia in the respiratory track of cystic
      fibrosis patients, suggests a putative role of this EPS in a pathologic context.

PMID- 11506921
TI  - Multiple phosphorylation of membrane-associated calcium-dependent protein
      serine/threonine kinase in Streptomyces fradiae.
AB  - In Streptomyces fradiae, calcium ions induce alterations in intensity and
      specificity of the secondary metabolism and stimulate aerial mycelium formation
      and sporulation. Using in vitro labeling, we demonstrate that in S. fradiae in
      the late exponential growth phosphorylation of 65-kDa membrane-associated protein
      is also influenced by Ca(2+) added exogenously. Calcium ions at physiological
      concentration stimulate intensive Ca(2+)-dependent phosphorylation of 65-kDa
      protein at multiple sites on serine, threonine, and tyrosine residues. Assay of
      protein kinases in situ demonstrated in the fraction of membrane-associated
      proteins the presence of two autophosphorylating protein serine/threonine kinases
      with molecular masses of 127 kDa and 65 kDa. Autophosphorylation of both proteins
      is also Ca(2+)-dependent.

PMID- 11506922
TI  - Construction of a series of mutants lacking all of the four major mex operons for
      multidrug efflux pumps or possessing each one of the operons from Pseudomonas
      aeruginosa PAO1: MexCD-OprJ is an inducible pump.
AB  - We constructed a series of deletion mutants lacking all of the four major mex
      operons for Mex multidrug efflux pumps or possessing each one of the operons from
      Pseudomonas aeruginosa PAO1. The drug specificity of MexAB-OprM, MexXY-OprM and
      MexCD-OprJ was investigated. Surprisingly, we found that the MexCD-OprJ was an
      inducible pump, inducers of which were tetraphenylphosphonium chloride, ethidium
      bromide, rhodamine 6G and acriflavine. Fluoroquinolones, chloramphenicol,
      erythromycin and tetracycline were not inducers although they were substrates of
      MexCD-OprJ.

PMID- 11506923
TI  - Characterization of a new feedback-resistant 3-deoxy-D-arabino-heptulosonate 7
      phosphate synthase AroF of Escherichia coli.
AB  - Tyrosine feedback-inhibits the 3-deoxy-D-arabino-heptulosonate 7-phosphate (DAHP)
      synthase isoenzyme AroF of Escherichia coli. Here we show that an Asn-8 to Lys-8
      substitution in AroF leads to a tyrosine-insensitive DAHP synthase. This mutant
      enzyme exhibited similar activities (v=30-40 U mg(-1)) and substrate affinities
      (K(m)(erythrose-4-phosphate)=0.5 mM, positive cooperativity with respect to
      phospho(enol)pyruvate) as the wild-type AroF, but showed decreased
      thermostability. An engineered AroF enzyme lacking the seven N-terminal residues
      also was tyrosine-resistant. These results strongly suggest that the N-terminus
      of AroF is involved in the molecular interactions occurring in the feedback
      inhibition mechanism.

PMID- 11506924
TI  - Oral immunisation against classical swine fever (CSF): onset and duration of
      immunity.
AB  - In an experimental study, onset and duration of immunity after oral immunisation
      of pigs with a classical swine fever (CSF) live virus vaccine based on the strain
      "C" has been evaluated. Sixteen weaner piglets (group 1) were orally instilled by
      syringe with the content of one vaccine bait whereas eighteen piglets (group 2)
      were fed with one bait. Six unvaccinated piglets represented the control group
      (group 3). The pigs having 2, 4, 6 and 10 days post vaccination (p.v.) were
      challenged with the highly virulent CSF virus (CSFV) strain "Koslov" to detect
      onset of immunity. After oral instillation of vaccine (group 1) the pigs were
      protected from a clinical infection 4 days p.v. One of four piglets reacted for a
      short time with an increase of body temperature. In group 2, a partial protection
      was already detected on day 2 p.v. On day 10 p.v., all animals were resistant to
      an experimental challenge infection. No protective neutralising antibodies were
      elicited until day 10 p.v. in both groups. Three animals of each group vaccinated
      orally against CSF were challenged approximately 6 and 10 months p.v. to evaluate
      duration of immunity. All vaccinated pigs developed neutralising antibodies and
      showed a protective immunity against an infection with CSFV until 10 months p.v.
      Furthermore, no vaccinated animal developed a viraemia after challenge.
      Altogether, 5 of 34 vaccinated pigs as well as all controls died after infection
      and showed typical gross lesions for CSF. The tonsils of the surviving pigs were
      negative for viral antigen by immunofluorescence.

PMID- 11506925
TI  - Characteristics of necrotoxigenic Escherichia coli isolated from septicemic and
      diarrheic calves between 1958 and 1970.
AB  - A total of 434 Escherichia coli isolated from septicemic calves between 1958 and
      1965 and 430 E. coli isolated from diarrheic calves between 1967 and 1970 were
      studied by colony hybridisation and PCR assays for the presence of the cnf1- and
      the cnf2-like genes. They were also studied for the presence of genes coding for
      putative virulence factors associated with the CNF toxins including F17-, Pap-
      and Sfa-fimbrial adhesins and the recently described CDT-III toxin and AfaVIII
      afimbrial adhesin. Thirty (7%) of the 434 septicemic strains were positive for
      CNF by colony hybridisation. Twenty-six were confirmed as necrotoxigenic E. coli
      type 2 (NTEC2) and four as NTEC1 by PCR. Thirty-five (8%) of the 430 diarrheic
      strains were positive for CNF by colony hybridisation. Five of them were studied
      by PCR and confirmed as NTEC1. The 26 septicemic NTEC2 strains and 20 of the 35
      diarrheic NTEC including three of the five NTEC1 were positive for CDT-III. All
      adhesins studied were present in NTEC as well as in non-NTEC. NTEC1 were mainly
      Pap-, Sfa- and/or Afa8-positive, whereas NTEC2 were mainly F17- and/or Afa8
      positive. This study shows that necrotoxigenic E. coli with their associated
      adhesins and toxins were present in calves as early as 1958, but their prevalence
      seems to have increased since that time.

PMID- 11506926
TI  - Development and validation of an ELISA for the detection of leptospire-specific
      antibodies in rodents.
AB  - An enzyme-linked immunosorbent assay (ELISA) for the detection of IgG antibodies
      in rodents was developed and validated with the microscopic agglutination test
      (MAT) and leptospiral cultures. Sonicated antigen from cultures of serovars
      tarassovi and pyrogenes was used. As conjugate, a combination of anti-rat and
      anti-hamster IgG labeled with peroxidase was used. The optimal cut-off point was
      determined by plotting the sensitivity and specificity for various cut-off point
      values by means of receiver operating characteristic (ROC) curve. Concordance
      between ELISA and each of the MAT titers was measured by kappa (kappa).
      Proportions of positive results were compared by means of McNemar's test. Total
      214 rodents were trapped, but only 117 could be processed by the three techniques
      (culture, ELISA, MAT; 1:20, 1:40, 1:50) and used for statistical analysis.
      Although, MAT titers in rodents infected with the serogroup Ballum tended to be
      lower than those infected with the serogroup Icterohaemorrhagiae, all (20/20)
      were ELISA-positive and almost all (19/20) were MAT-positive.The percentage of
      positive results obtained by ELISA, 47.0% exceeded significantly the 40.2%
      obtained by MAT (1:50). Difference between ELISA and MAT (1:40) was not
      significant and no differences were observed between ELISA and MAT (1:20).
      Agreement, specificity, sensitivity and the consequent area under the ROC curve
      between ELISA and MAT were higher as MAT cut-off points were lowered, being
      optimal at 1:20. The fact that differences between ELISA and MAT were significant
      at 1:50, but not at 1:40 or 1:20, supports the suggestion that lower MAT titers
      should be considered positive in rodents. The ELISA developed to detect
      leptospire-specific antibodies had optimal sensitivity and specificity in
      relation to MAT and it is concluded that it may constitute a very useful
      indicator for epidemiological purposes of past or present leptospiral infection
      in rodents.

PMID- 11506927
TI  - Lawsonia intracellularis: getting inside the pathogenesis of proliferative
      enteropathy.
AB  - Although proliferative enteropathy (PE) has been recognised for several decades,
      Lawsonia intracellularis, the aetiological agent, was identified formally in only
      1995. This organism is both highly fastidious and obligately intracellular
      bacterium, characteristics which have inevitably restricted investigations in all
      aspects of its biology. Despite these limitations, advances have been made in
      characterising and understanding L. intracellularis-host interaction both in vivo
      and in vitro. Based upon evidence provided by mainly pathological and
      histological investigations conducted to date, we review salient features of our
      current understanding of processes involved throughout the course of infection by
      this unique pathogen.

PMID- 11506928
TI  - Transmission of opportunistic pathogens in a veterinary teaching hospital.
AB  - Acinetobacter baumannii, Enterococcus faecalis, Enterococcus faecium, and
      Staphylococcus intermedius isolates from infected surgical wounds and other types
      of infections in a veterinary teaching hospital were typed by pulsed field gel
      electrophoresis. A first cluster of infections with a multiresistant A. baumannii
      strain was observed in dogs and cats in 1998-1999. This strain disappeared after
      cleaning and disinfection of the companion animals intensive care unit. It was
      followed in 2000 by a second multiresistant strain, which caused another cluster
      of infections and was also transmitted to a patient in the nearby horse clinic.
      Transmission of a multiresistant E. faecium strain between two cats with surgical
      wound infections was also observed during the same period. No multiresistant S.
      intermedius strain was observed during this time and transmission of this
      organism between patients did not seem to occur. The present study demonstrates
      the potential for hospital nosocomial resistance problems in veterinary medicine
      similar to those encountered in human medicine. The results suggest that the
      epidemiology of nosocomial infections with A. baumannii and E. faecium may differ
      from that of S. intermedius infections and that preventive measures may have to
      be adapted to the problem organism.

PMID- 11506929
TI  - Random amplification of polymorphic DNA and phenotypic typing of Zimbabwean
      isolates of Pasteurella multocida.
AB  - Eighty-one isolates presumptively identified as Pasteurella multocida from a
      variety of diseases in animals in Zimbabwe were subjected to biochemical
      characterization, capsular typing and RAPD analysis. The majority of isolates
      (over 80%) were assigned into named taxa and were predominantly P. multocida
      subsp. multocida and P. multocida subsp. septica, whilst the remainder were
      unassigned. Serogroup A was predominant among the three capsular types (A, B and
      D) of P. multocida detected. Three main RAPD clusters and three subclusters were
      observed among the majority of isolates (93.8%), whilst the remainder was found
      to be weakly related. Nine different groups of strains with similar RAPD profiles
      (100% similarity) were also observed. The reference strain of capsular serogroup
      F clustered with the reference strain of P. multocida subsp. septica, whilst all
      other serogroups clustered with reference strains of subsp. multocida and
      gallicida. Notably, serogroups A and D were observed to be closely related to the
      reference strain of subsp. multocida. The relationship between biotype, capsular
      type, host origin and disease manifestation was not clear-cut. However, most pig
      isolates of subsp. multocida clustered together as did most cattle isolates of
      subsp. multocida. RAPD tended to separate subsp. multocida from septica.

PMID- 11506930
TI  - Two new variants of the Rhodococcus equi virulence plasmid, 90 kb type III and
      type IV, recovered from a foal in Japan.
AB  - This report describes the discovery of two new virulence plasmid types from a
      crossbred foal with Rhodococcus equi pneumonia in Kumamoto died with severe R.
      equi pneumonia and ulcerative enteritis. R. equi was isolated in large numbers
      and isolates from the foal were investigated for the presence of virulence
      associated 15-17 kDa antigens (VapA) by colony blotting, using the monoclonal
      antibody 10G5, and by gene coding for VapA by PCR. Plasmid DNAs extracted from
      the isolates were digested with restriction endonucleases BamHI, EcoRI, EcoT22I,
      and HindIII. The digestion patterns that resulted divided the plasmids of these
      isolates into two closely related types. The digestion patterns were then
      compared with eight representative virulence plasmid types (85 kb types I, II,
      III and IV, 87 kb types I and II, 90 kb types I and II), which have already been
      reported. None of the EcoRI and EcoT22I digestion patterns of the eight
      representative plasmids matched those of the two plasmid types. We tentatively
      designated these new plasmid types as 90 kb type III and type IV, since HindIII
      and BamHI digestion patterns of the two plasmid types were identical with those
      of a 90 kb type I plasmid. This study, demonstrated that there are at least 10
      distinct but closely related plasmids present in isolates from horses in the
      world.

PMID- 11506931
TI  - Differentiation of Fusobacterium necrophorum subspecies from bovine pathological
      lesions by RAPD-PCR.
AB  - Nineteen strains from bovine abscesses identified as Fusobacterium necrophorum by
      the VPI method were examined by other methods. The API 20A test kit characterized
      all 19 strains as F. necrophorum. Seven of the strains had haemagglutinating
      activity and were classified as F. necrophorum subspecies necrophorum, and the
      remaining, 12 nonhaemagglutinating strains, were classified as F. necrophorum
      subspecies funduliforme. We used RAPD-PCR with a 10-mer oligonucleotide primer,
      W1L-2, to confirm this differentiation of the two subspecies. These results
      suggest that random amplified polymorphic DNA polymerase chain reaction (RAPD
      PCR) with a suitable primer can be used as a new tool for the differentiation of
      F. necrophorum subspecies isolated from bovine pathological lesions.

PMID- 11506933
TI  - Subcortical neural coding mechanisms for auditory temporal processing.
AB  - Biologically relevant sounds such as speech, animal vocalizations and music have
      distinguishing temporal features that are utilized for effective auditory
      perception. Common temporal features include sound envelope fluctuations, often
      modeled in the laboratory by amplitude modulation (AM), and starts and stops in
      ongoing sounds, which are frequently approximated by hearing researchers as gaps
      between two sounds or are investigated in forward masking experiments. The
      auditory system has evolved many neural processing mechanisms for encoding
      important temporal features of sound. Due to rapid progress made in the field of
      auditory neuroscience in the past three decades, it is not possible to review all
      progress in this field in a single article. The goal of the present report is to
      focus on single-unit mechanisms in the mammalian brainstem auditory system for
      encoding AM and gaps as illustrative examples of how the system encodes key
      temporal features of sound. This report, following a systems analysis approach,
      starts with findings in the auditory nerve and proceeds centrally through the
      cochlear nucleus, superior olivary complex and inferior colliculus. Some general
      principles can be seen when reviewing this entire field. For example, as one
      ascends the central auditory system, a neural encoding shift occurs. An emphasis
      on synchronous responses for temporal coding exists in the auditory periphery,
      and more reliance on rate coding occurs as one moves centrally. In addition, for
      AM, modulation transfer functions become more bandpass as the sound level of the
      signal is raised, but become more lowpass in shape as background noise is added.
      In many cases, AM coding can actually increase in the presence of background
      noise. For gap processing or forward masking, coding for gaps changes from a
      decrease in spike firing rate for neurons of the peripheral auditory system that
      have sustained response patterns, to an increase in firing rate for more central
      neurons with transient responses. Lastly, for gaps and forward masking, as one
      ascends the auditory system, some suppression effects become quite long (echo
      suppression), and in some stimulus configurations enhancement to a second sound
      can take place.

PMID- 11506934
TI  - Electrophysiological responses of cochlear root neurons.
AB  - Cochlear root neurons (CRNs) are second-order neurons interspersed among the
      fibers of the cochlear nerve in certain rodents. They project, among other
      nuclei, mainly to the pontine reticular nucleus, and participate in the acoustic
      startle response (ASR), a short-latency motor reflex initiated by sudden intense
      sounds. The sound-evoked activity of CRNs has not previously been described. Here
      we describe extracellular responses of CRNs located in the infranuclear portion
      of the cochlear nerve root. CRNs exhibited secure responses to tone bursts, with
      first-spike latencies of approximately 2.2 ms. The characteristic frequencies of
      the recorded CRNs were about 30 kHz, and the best-characterized CRN had a
      threshold of 10 dB sound pressure level and sharpness of tuning similar to that
      of cochlear nerve fibers. The peristimulus time histograms were primary-like with
      notch. The observed response properties were consistent with the suggestion that
      CRNs provide the short-latency acoustic input to the reticular formation that
      leads to an ASR.

PMID- 11506935
TI  - The laminins in the murine inner ear: developmental transitions and expression in
      cochlear basement membranes.
AB  - The laminins are a family of heterotrimeric extracellular matrix molecules that
      form suprastructural networks in basement membranes and elsewhere. They interact
      with integrin receptors, playing key roles in modulating programs of
      cytodifferentiation and maintaining tissue homeostasis in animals. Earlier
      studies have demonstrated an extensive laminin network in both the developing and
      adult cochlea, primarily associated with the basement membranes. These studies,
      however, did not address the laminin chain composition of these networks. In this
      study, we used antibodies specific for the known laminin chains to examine the
      composition of laminins in both the developing and adult murine cochlea. The
      results illustrate a complex and dynamic postnatal developmental regulation
      pattern for most of these chains, and suggest that an unusually large number of
      laminin heterotrimers are present in both the developing and adult cochlea. The
      laminin composition at postnatal day 2 is relatively simple. By postnatal day 7,
      however, activation of several laminin chains results in a very complex laminin
      composition. In the basement membrane underlying the region of the basilar
      membrane under the developing organ of Corti, eight of the 11 known basement
      membrane laminins are possible by co-localization inference. Dynamic changes in
      expression continue through day 14, but simplify by adulthood. Thus, the most
      dynamic period for laminin expression in the mouse cochlea coincides with
      terminal cytodifferentiation of the cochlear epithelial structures. Considering
      the well established role of laminins in regulating both embryonic and organ
      development in other systems, these data suggest a closer look at the role of the
      laminins in cochlear development and function may be warranted.

PMID- 11506936
TI  - Selective expression of aquaporin 1, 4 and 5 in the rat middle ear.
AB  - The middle ear cavity is an air-filled space that must be maintained for
      effective sound transmission to the inner ear. To examine the mechanisms of water
      homeostasis in the middle ear, we investigated whether aquaporins (AQPs), a
      family of water-permeable channels, were expressed in the middle ear. Reverse
      transcription-polymerase chain reaction and immunoblot analyses revealed that
      mRNAs encoding AQP1, 4 and 5 (but not 2 or 3) subtypes were expressed in rat
      middle ear epithelium; AQP1, 4 and 5 were detected as 28-, 30- and 30-kDa
      proteins, respectively. Immunohistochemical analysis showed that AQP1 was
      localized at capillary endothelial cells and fibroblasts in lamina propria
      mucosae; AQP4 was present solely at the basolateral membrane of ciliated cells,
      whereas AQP5 was on the apical surface of ciliated cells as well as of flat and
      columnar epithelial cells. The characteristic different localizations of AQP1, 4
      and 5 subtypes in the middle ear suggest that middle ear water homeostasis
      requires the coordinated operation of these AQPs.

PMID- 11506937
TI  - Human auditory middle latency responses: influence of stimulus type and
      intensity.
AB  - Human auditory middle latency responses (MLR) to click and tone pip stimuli of
      different intensities were recorded by means of magnetoencephalography (MEG) and
      electroencephalography (EEG). Clicks elicited larger responses with significantly
      shorter latencies than the tone pips at the same intensity in dB sensation level
      (SL). Most MLR amplitudes increased and their latencies decreased with increasing
      stimulus intensity for both types of stimulation. Pa and Nb amplitudes saturated
      at intensities of 60 dB SL in the case of click stimulation. The shorter
      latencies of MLR evoked by the click were explained by its short rise time and
      the high frequency content of its spectrum. MEG source analysis yielded MLR
      sources which were clearly different from those of the slow cortical wave N1.
      They seem to be located in primary auditory areas along Heschl's gyrus.

PMID- 11506938
TI  - Simulated hair cell transduction of quasi-frequency-modulated and amplitude
      modulated tones.
AB  - This paper describes a method for calculating the effect of simulated hair cell
      transduction on (i) a quasi-frequency-modulated (quasi-FM) tone and on (ii) an
      amplitude-modulated (AM) tone. The main finding is that the effect of the
      transduction on AM and quasi-FM (which have the same power spectra but whose
      phase spectra differ), is to produce different power spectra.

PMID- 11506939
TI  - The effects of temporal asymmetry on the detection and perception of short
      chirps.
AB  - There is an intriguing contrast between the physiological response to short
      frequency sweeps in the brainstem and the perception produced by these sounds.
      Dau et al. (2000) demonstrated that optimised chirps with increasing
      instantaneous frequency (up-chirps), designed to compensate for spatial
      dispersion along the cochlea, enhance wave V of the auditory brainstem response
      (ABR), by synchronising excitation of all frequency channels across the basilar
      membrane. Down-chirps, that is up-chirps reversed in time, increase cochlear
      phase delays and therefore result in a poor ABR wave V. In this study, a set of
      psychoacoustical experiments with up-chirps and down-chirps has been performed to
      investigate how these phase changes affect what we hear. The perceptual contrast
      is different from what was reported at the brainstem level. It is the down-chirp
      that sounds more compact, despite the poor synchronisation across channels and
      phase delays up to 20 ms. The perceived 'compactness' of a sound is apparently
      more determined by the fine structure of excitation within each peripheral
      channel than by between-channel phase differences. This suggests an additional
      temporal integration mechanism at a higher stage of auditory processing, which
      effectively removes phase differences between channels.

PMID- 11506940
TI  - Age-related temporal processing speed deterioration in auditory cortex.
AB  - A common problem among the elderly is a difficulty in discriminating speech
      sounds. One factor that may contribute to this is a deterioration in the ability
      to process dynamic aspects of speech such as formant transitions. For the aging
      auditory system, this deterioration in temporal processing speed may be manifest
      as a deficit in encoding time-varying sounds that contain rapidly changing
      frequencies such as formant transitions. The primary goal of this study was to
      explore the neural basis of the effects of aging on temporal processing speed. To
      this end, single units were recorded from the auditory cortex of young and aged
      rats in response to frequency-modulated (FM) sweeps that changed from trial to
      trial in both direction and speed. Results showed that the majority of cells
      recorded from young rats responded most vigorously to fast and medium speeds. By
      contrast, the majority of units recorded from aged animals responded best to slow
      speeds. For preferred direction of FM sweep, similar results were observed for
      both age groups, namely, approximately half of the units exhibited a direction
      selective response. The results of the present study demonstrate an age-related
      decrease in the rate of change of frequency that can be processed by the auditory
      cortex.

PMID- 11506941
TI  - Cortical reorganization in patients with high frequency cochlear hearing loss.
AB  - Animal research has shown that tonotopic representation in the auditory cortex is
      not statically fixed in the adult organism but can be altered after
      deafferentation. The present study examines the plasticity of the human auditory
      cortex in patients with high frequency cochlear hearing loss by means of
      magnetoencephalographic measurements. The data show that the cortical map can
      reorganize such that cortical neurons deprived of their usual most sensitive
      afferent input now respond to tone frequencies adjacent to the frequency range of
      the partial hearing loss. The results suggest that deafferentation due to
      cochlear damage in adults may lead to functional reorganization of auditory
      cortical structures.

PMID- 11506942
TI  - The total number of neurons and calcium binding protein positive neurons during
      aging in the cochlear nucleus of CBA/CaJ mice: a quantitative study.
AB  - The quantitative stereological method, the optical fractionator, was used for
      determining the total number of neurons and the total number of neurons
      immunostained with parvalbumin, calbindin-D28k (calbindin), and calretinin in the
      dorsal and posteroventral cochlear nucleus (DCN and PVCN) in CBA/CaJ (CBA) mice
      during aging (1-39 months old). CBA mice have only a modest sensorineural
      pathology late in life. An age-related decrease of the total number of neurons
      was demonstrated in the DCN (r=-0.54, P<0.03), while the total number of neurons
      in the PVCN did not show any significant age-related differences (r=0.16,
      P=0.57). In the DCN 5.5% of neurons were parvalbumin positive in the very old (30
      39 months) mice, vs. 2.2% in the 1 month old mice. In the DCN 3% of the neurons
      were calbindin immunopositive in the 30-39 months mice compared to 1.9% in the 1
      month old group. In the PVCN, 20% of the neurons in the very old mice were
      parvalbumin immunopositive, compared to 12% in the young mice. Calbindin did not
      show any significant age-related differences in the PVCN. The total number of
      calretinin immunopositive neurons both in the DCN and PVCN did not show any
      significant change with increasing age. In conclusion, the total neuronal number
      in the DCN and PVCN was age-related and region-specific. While the neuronal
      number in the DCN and PVCN was decreased or unchanged, respectively, the calcium
      binding protein positive neuronal number showed a graded increase during aging in
      a region-specific and protein-specific manner.

PMID- 11506943
TI  - Detection of apoptotic change in the lipopolysaccharide (LPS)-treated cochlea of
      guinea pigs.
AB  - This study was undertaken to examine, electrophysiologically and
      immunohistochemically, the effect of endotoxin on the guinea pig cochlea. A
      bacterial endotoxin (lipopolysaccharide, LPS, 5 mg/ml, 0.2 ml) was injected into
      the middle ear trans-tympanically. The electrocochleograms were continuously
      recorded from before to 48 h after the injection with an electrode inserted into
      the facial canal. Then, the animals were sacrificed by intracardiac perfusion of
      a fixative, temporal bones were removed and immunohistochemically stained for
      single-stranded DNA (ssDNA) and caspase 3 (CPP32). ssDNA was detected at 48 h in
      the stria vascularis and spiral ligament. CPP32 was observed in the stria
      vascularis, the spiral ligament and the organ of Corti. The threshold of the
      compound action potential increased significantly at 48 h in the LPS group. These
      results suggest that the activation of CPP32 and fragmentation of DNA are
      involved in the dysfunction of the cochlea observed under inflammatory
      conditions.

PMID- 11506944
TI  - Estrogen acutely inhibits ion transport by isolated stria vascularis.
AB  - We investigated the nongenomic effects of female sex steroid hormones on the
      short circuit current (I(sc,probe)) across gerbil stria vascularis using the
      voltage-sensitive vibrating probe. The strial marginal cell epithelial layer
      produces I(sc,probe) by secreting K+ via I(Ks) channels in the apical membrane.
      Application of 17beta-estradiol (E2) caused a decrease of I(sc,probe) in a dose
      dependent manner (10 nM-10 microM) within seconds. Tamoxifen, a competitive
      inhibitor of the intracellular estrogen receptor, did not change the inhibitory
      effect of E2. Activation of I(Ks) channels by 4,4'-diisothiocyanatostilbene-2,2'
      disulfonic acid in the presence and absence of E2 was used to test the mechanism
      of action. The results were consistent with a direct inhibitory effect of E2 on
      the I(Ks) channels. By contrast, progesterone caused a transient increase of
      I(sc,probe). These results suggest that E2 decreases secretion of K+ by
      inhibition of I(Ks) channels via a nongenomic mechanism at concentrations near
      those occurring under some physiologic conditions while progesterone caused only
      transient effects on I(sc,probe).

PMID- 11506945
TI  - Early bilateral deafening prevents calretinin up-regulation in the dorsal cortex
      of the inferior colliculus of aged CBA/CaJ mice.
AB  - This study was conducted to test the hypothesis that age-related calretinin (CR)
      up-regulation seen in the dorsal cortex of the inferior colliculus (ICdc) of old
      hearing CBA mice is dependent upon neural activity within the auditory pathway.
      We tested this hypothesis by bilaterally deafening young CBA/CaJ mice with
      kanamycin, and then aging them until 24 months. This manipulation mimics the lack
      of sound-evoked auditory activity experienced by old C57BL/6J mice, who are deaf
      and do not show CR up-regulation with age. Cell counts revealed that the density
      of CR+ cells in the ICdc of old hearing CBA mice was statistically different from
      old deafened CBA mice raised under identical conditions. Old hearing CBAs
      possessed an average of 27.54 more CR+ cells/100 microm2 than old deafened CBAs.
      When old deafened CBAs were compared to young hearing CBAs, young hearing C57s,
      and old deaf C57s, there was no significant difference in mean CR+ cell density
      in ICdc. Thus, only the old normal hearing CBAs showed an increase in CR+ cells
      with age, supporting the hypothesis that CR up-regulation depends upon sound
      evoked activity. Moreover, these results demonstrate that up-regulation of CR
      expression was not simply due to a mouse strain difference.

PMID- 11506946
TI  - Effect of inner and outer hair cell lesions on electrically evoked otoacoustic
      emissions.
AB  - When the cochlea is stimulated by a sinusoidal current, the inner ear emits an
      acoustic signal at the stimulus frequency, termed the electrically evoked
      otoacoustic emission (EEOAE). Recent studies have found EEOAEs in birds lacking
      outer hair cells (OHCs), raising the possibility that other types of hair cells,
      including inner hair cells (IHCs), may generate EEOAEs. To determine the relative
      contribution of IHCs and OHCs to the generation of the EEOAE, we measured the
      amplitude of EEOAEs, distortion product otoacoustic emissions (DPOAEs), the
      cochlear microphonic (CM) and the compound action potential (CAP) in normal
      chinchillas and chinchillas with IHC lesions or IHC plus OHC lesions induced by
      carboplatin. Selective IHC loss had little or no effect on CM amplitude and
      caused a slight reduction in mean DPOAE amplitude. However, IHC loss resulted in
      a massive reduction in CAP amplitude. Importantly, selective IHC lesions did not
      reduce EEOAE amplitude, but instead, EEOAE amplitude increased at high
      frequencies. When both IHCs and OHCs were destroyed, the amplitude of the CM,
      DPOAE and EEOAE all decreased. The increase in EEOAE amplitude seen with IHC loss
      may be due to (1) loss of tonic efferent activity to the OHCs, (2) change in the
      mechanical properties of the cochlea or (3) elimination of EEOAEs produced by
      IHCs in phase opposition to those from OHCs.

PMID- 11506947
TI  - Spatiotemporal expression of otogelin in the developing and adult mouse inner
      ear.
AB  - Using a PCR-based subtractive method on cDNA from 2-day-old mouse cochlea, we
      identified a gene encoding otogelin, Otog, an inner ear specific glycoprotein
      expressed in all acellular structures. Here, we provide evidence that otogelin is
      detected as early as embryonic day 10 in the otic vesicle. At this stage,
      otogelin is detected in the epithelial cells which do not overlap with the myosin
      VIIA-expressing cells, namely the precursors of the hair cells, thus arguing for
      an early commitment of the two cell populations. Analysis of otogelin
      spatiotemporal cell distribution allows a molecular tracing for the contribution
      of the cochlear and vestibular inner ear supporting cells to the formation of the
      acellular structures. Throughout embryonic and adult life, the expression of the
      otogelin gene as monitored by LacZ inserted into Otog, and the abundance of the
      protein are greater in the vestibule than in the cochlea. In adult, otogelin is
      still produced by the vestibular supporting cells, which argues for a continuous
      process of otogelin renewal in the otoconial membranes and cupulae. In contrast,
      in the tectorial membrane, otogelin should be a long-lasting protein since both
      the otogelin gene and protein were almost undetectable in adult cochlear cells.
      The data are consistent with the requirement for otogelin in the attachment of
      the otoconial membranes and cupulae to their corresponding sensory epithelia as
      revealed in Otog -/- mice.

PMID- 11506948
TI  - Functional magnetic resonance imaging of human pontine auditory pathway.
AB  - The purpose of this study is to visualize brainstem auditory pathways by
      functional magnetic resonance imaging (fMRI). Eighteen healthy volunteers (age 28
      to 42 years) with normal hearing function underwent fMRI examination on a 1.5
      Tesla imaging system (Philips, Best, The Netherlands) with periodic click
      stimulation. Blood oxygen level dependent images were obtained using a three
      dimensional EPI sequence with shifted echo technique (principles of echo shifting
      with a train of observations). Control scans without click stimulation were
      obtained in the identical setting. Cross correlation activation maps were
      calculated using a postprocessing tool (Philips). They were matched with anatomic
      slices of identical orientation and thickness. Five of 18 subjects were excluded
      because of motion artifacts. In 4/13 significant activation was observed at the
      root entry zone of the ipsilateral acoustic nerve corresponding to the cochlear
      nuclei. In 11/13 subjects, significant activation was found in the same slice
      contralaterally close to the floor of the 4th ventricle, corresponding to the
      expected region of the superior olivary nucleus. Activation of the rostral parts
      of the auditory pathway (inferior colliculus, medial geniculate body) was not
      found. In the absence of the stimulus no activation occurred in these structures.
      It was concluded that activation of the brainstem auditory pathways by click
      stimuli can be visualized by fMRI.

PMID- 11506949
TI  - Aminoglycoside ototoxicity in adult CBA, C57BL and BALB mice and the Sprague
      Dawley rat.
AB  - The availability of genetic information, transgenic and knock-out animals make
      the mouse a primary model in biomedical research. Aminoglycoside ototoxicity,
      however, has rarely been studied in mature mice because they are considered
      highly resistant to the drugs. This study presents models for kanamycin
      ototoxicity in adult CBA/J, C57BL/6 and BALB/c mouse strains and a comparison to
      Sprague-Dawley rats. Five-week-old mice were injected subcutaneously twice daily
      with 400-900 mg kanamycin base/kg body weight for 15 days. Kanamycin induced dose
      dependent auditory threshold shifts of up to 70 dB at 24 kHz as measured by
      auditory brain stem-evoked responses. Vestibular function was also affected in
      all strains. The functional deficits were accompanied by hair cell loss in both
      cochlear and vestibular neurosensory epithelia. Concomitant administration of the
      antioxidant 2,3-dihydroxybenzoate significantly attenuated the kanamycin-induced
      threshold shifts. In adult male Sprague-Dawley rats, doses of 1 x 500 mg or 2 x
      300 mg kanamycin base/kg body weight/day x 14 days induced threshold shifts of
      approximately 50 dB at 20 kHz. These were accompanied by loss of outer hair
      cells. The order of susceptibility, BALB>CBA>C57, was not due to differences in
      the pharmacokinetics of kanamycin. It also did not correlate with the presence of
      Ahl/Ahl2 genes which predispose C57 and BALB strains, respectively, to
      accelerated age-related hearing loss. Pigmentation, however, paralleled this rank
      order suggesting an influence of melanin on cochlear antioxidant status.

PMID- 11506950
TI  - Quality assurance in surgical oncology (QASO) within the European Organization
      for Research and Treatment of Cancer (EORTC): current status and future
      prospects.
AB  - The European Organization for Research and Treatment of Cancer (EORTC) has a long
      history in the development of quality assurance, in particular in radio- and
      chemotherapy. Quality assurance in surgical oncology is considered to be more
      complicated, because it is a multistep procedure depending on the individual.
      Because of the growing importance of the quality of surgical intervention in the
      multi-modality treatment approach of most cancers, the EORTC recently decided to
      investigate the current status of quality assurance programmes, both outside and
      within, the EORTC. The review of EORTC involvement in this area has been
      conducted on the basis of interviews with subcommittee chairmen and Data Center
      teams of the EORTC clinical research groups. In addition, clinical trial
      protocols, case report forms (CRFs) and publications by the EORTC groups related
      to this field were considered as possible sources of information. Several methods
      have been used or are currently under investigation to ensure the quality of
      surgery within clinical trials. These include review of reported data,
      standardisation of surgery and pathology forms, training sessions and site
      visits. However, there has been no attempt to harmonise these initiatives across
      the different medical specialties. The EORTC will have to address this problem
      within its short-term scientific strategy.

PMID- 11506951
TI  - Oestrogen and vitamin D receptor (VDR) genotypes and the expression of ErbB-2 and
      EGF receptor in human rectal cancers.
AB  - Oestrogen/oestrogen receptor (ER) and vitamin D/vitamin D receptor (VDR) systems
      have been implicated in the pathogenesis of colorectal cancers. The expression of
      erbB-2 and epidermal growth factor receptor (EGFR) in colorectal cancers has been
      suggested to have diagnostic and prognostic significance. In our study, XbaI and
      PvuII polymorphisms of the ER gene and the BsmI polymorphism of the VDR gene were
      studied in 56 Caucasian patients with rectal cancer. The relationship between the
      ER and VDR genotypes and the expression of oncogenes was also investigated. The
      presence of the x allele of ER gene significantly correlated with the
      overexpression of the erbB-2 and EGFR oncogenes. Significantly increased erbB-2
      expression was observed in patients with the VDR B allele. The XXbb allelic
      combination of the ER/VDR genes was associated with a significantly lower erbB-2
      expression, whereas in the other genotypes significantly higher oncogene
      expression was seen. Our data raise the possibility that ER/VDR gene
      polymorphisms accompanied by variable oncogene expression might influence the
      pathogenetic processes of colorectal cancers.

PMID- 11506952
TI  - Expression of cyclooxygenase-2 (COX-2) mRNA in human colorectal adenomas.
AB  - Cyclooxygenase-2 (COX-2) is an important target for the suppression of colorectal
      tumorigenesis by non-steroidal anti-inflammatory drugs (NSAIDs). To evaluate the
      role of COX-2 in human sporadic colorectal adenomas, COX-2 mRNA expression was
      examined by reverse transcription-polymerase chain reaction (RT-PCR) in 63
      adenomas. COX-2 mRNA was detected in all the adenomas at higher levels than in
      normal colorectal mucosa (P<0.001). Levels of expression in the adenomas were
      correlated with their size (P=0.019), but no relationships were demonstrable
      between COX-2 expression and adenoma location, macroscopically observed
      configuration or microscopic degree of dysplasia. These findings suggest that COX
      2 plays an important role in the growth of sporadic colorectal adenomas.

PMID- 11506953
TI  - Abnormal E-cadherin expression and prostate cell blood dissemination as markers
      of biological recurrence in cancer.
AB  - Until now, no molecular parameter has been available for predicting the
      metastatic potential of prostate tumours, which leaves their outcome uncertain
      despite an apparent benign histology or early stage. Abnormal expression of
      adhesion molecules, such as E-cadherin, can be contributing factors for increased
      invasiveness and metastatic potential. Histological analysis for E-cadherin
      expression was carried out on paraffin-embedded tumour tissues. Tumour metastatic
      potential was indirectly evaluated by detecting circulating prostate cells (CPC),
      using reverse transciptase-polymerase chain reaction (RT-PCR) and prostate
      specific membrane antigen (PSMA) as a target. Patients were followed-up for a
      median of 14 months (range 10--19 months) after surgery with serum prostate
      specific antigen (PSA) level measurement. Interestingly, 23 of 44 localised
      tumours exhibited aberrant E-cadherin expression. Prior to primary surgery, PSMA
      RT-PCR detected the spread of prostate cells to the blood in 24 patients.
      Statistical analysis showed that abnormal E-cadherin expression in the tumours
      was the only variable that was independently correlated with prostate cell
      dissemination in the blood (P<0.0001). In logistic regression analysis, abnormal
      E-cadherin expression was a significant independent predictor for a later
      biological relapse. This impaired adhesion status was clearly correlated with a
      haematogenous spread of the primary tumour cells. It could therefore be an
      objective way to restrict the indications for radical surgery to patients not
      presenting with this feature.

PMID- 11506954
TI  - Interleukin 8 and vascular endothelial growth factor -- prognostic factors in
      human gastric carcinomas?
AB  - Gastric carcinoma cells express potent angiogenic factors including vascular
      endothelial growth factor (VEGF). We previously reported that interleukin-8 (IL
      8) acts as an angiogenic factor for human gastric carcinomas. More recently, we
      found that IL-8 upregulates matrix metalloproteinase-9 (MMP-9) expression and
      increases invasive activity of gastric carcinoma cells. The purpose of this study
      was to determine whether the expression of IL-8 and VEGF correlates with
      clinicopathological parameters in human gastric carcinomas. IL-8 and VEGF
      expression levels were measured by an enzyme-linked immunosorbent assay (ELISA)
      in 56 gastric carcinomas and the surrounding normal mucosa. Macroscopic and
      histopathological tumour findings, presence of metastasis and prognosis were
      obtained from the patient records and endoscopic, surgical and pathological
      reports. IL-8 protein levels were higher in most neoplasms than in the
      corresponding normal mucosal tissue. In contrast, VEGF expression in the tumours
      was similar to that in normal mucosa. The IL-8 level in the neoplasms correlated
      significantly with the depth of invasion, venous invasion and lymphatic invasion.
      VEGF expression in the tumours correlated well with the depth of invasion and
      lymph node metastasis. No correlation between IL-8 and VEGF expression in the
      tumours was observed. The survival rates of patients with tumours displaying high
      IL-8 and VEGF expression levels were significantly lower (P<0.05) than those of
      patients with tumours displaying low IL-8 and VEGF expression. The results
      suggest that IL-8 and VEGF may be independent and important prognostic factors in
      human gastric carcinomas.

PMID- 11506955
TI  - Progesterone receptor isoform expression in human meningiomas.
AB  - The majority of meningiomas express the progesterone receptor (PR), and therefore
      meningiomas are considered to be progesterone-responsive. In addition, an
      association has been reported between PR and prognosis. At least two PR isoforms
      exist, PR-B (116--120 kDa) and PR-A (81 kDa), each of which are likely to have
      different biological functions. Knowledge of the differential expression of both
      isoforms is necessary to understand the effects of progesterone on meningioma
      growth. Therefore, in this study, PR-A and PR-B expression levels were determined
      in 61 human meningiomas by immunoblotting. Total PR expression levels were
      determined with a ligand binding assay (LBA) (total PR(LBA)). Both PR isoforms
      and an additional PR 78 kDa protein (PR-78) were expressed in the meningiomas.
      Meningiomas expressing more PR-A than PR-B had significantly higher total PR(LBA)
      levels (P<0.001). The PR-78 band intensity was negatively associated with that of
      PR-B (r(s)=-0.76, P<0.0001). PR-78 may represent an endogenous degradation
      product, but a similar regulation pathway in the biogenesis of both PR-B and PR
      78 is not excluded. Meningiomas contain both PR isoforms, but in highly variable
      ratios and this variability may have some biological significance. Most
      meningiomas express more PR-A than PR-B. Therefore in meningioma, assuming that
      PR-B is more transcriptionally active than PR-A, progesterone responsiveness
      could be based on transrepression rather than on transactivation of target genes,
      and progesterone blockade may only be effective in certain subsets of
      meningiomas.

PMID- 11506956
TI  - Chromosome 9 aberrations by fluorescence in situ hybridisation in bladder
      transitional cell carcinoma.
AB  - To investigate the role of the monosomy 9 in bladder carcinogenesis, 96 cases of
      superficial bladder transitional cell carcinoma (TCC) were studied and followed
      periodically for around 3 years (mean+/-standard error of the mean (SEM); 3.46+/
      0.34 years). Samples from bladder washings were analysed by fluorescent in situ
      hybridisation (FISH) to detect numerical anomalies of chromosome 9. Moreover, to
      evaluate the relative under representation of this chromosome, we detected
      numerical changes of chromosome 8 and DNA ploidy by flow cytometric analysis
      (FCM). Chromosome 8 copy number were related to FCM DNA ploidy and both were
      related with tumour grade. Monosomy 9 did not correlate with tumour grade, stage,
      chromosome 8 aneuploidies and abnormal DNA content, but correlated with tumour
      progression. Comparing the results in the primary and subsequent tumours, we
      observed an increase in the frequency of aneuploidies by FCM, associated with an
      increase of chromosome 8 polysomies. The mean chromosome 9 copy number/nucleus
      remained nearly the same in most of the primary and invasive tumours. Our results
      confirm that monosomy 9 is an early event and that it is retained during tumour
      progression and invasion and that the loss occurs before the tetraploidisation
      process. The relationship between the presence of a sub-population with monosomy
      9 and tumour progression suggests the presence of a region that could have a role
      in the progression of superficial bladder TCC.

PMID- 11506957
TI  - Compliance with follow-up and prognosis among patients with thin melanomas.
AB  - The aim of this study was to report on the compliance with follow-up among
      patients with thin melanomas. We also examined the prognosis of patients with
      recurrent disease and whether there were any differences in prognosis associated
      with the time between the last follow-up examination and the onset of recurrence.
      A retrospective analysis of the records of 513 consecutive patients (50.3% males,
      mean age: 52.8+/-16.9 years) with thin melanomas (<1.5 mm Breslow thickness) was
      carried out. The estimated cumulative proportion of patients who still continued
      their follow-up examinations 5 years after diagnosis of the primary tumour was
      55.3% (95% Confidence Interval (CI): 50.4--60.2%). The mean annual drop-out rate
      was 11.2%. The drop-out rate was similar for males and females and was not
      influenced by the patients' age or the tumour thickness. Among 263 patients who
      continued follow-up, 50.2% (n=132) were not compliant with the time schedule. 20
      patients presented with recurrent disease after a median of 35.9 months (25--75%
      percentiles: 16.7--46.5 months). Six patients who did not have a follow-up
      examination within 1 year before the onset of recurrence presented with more
      advanced disease and had a worse prognosis (median survival: 12.5 months, hazard
      ratio: 3.5, 95% CI: 1.1--17.1, P=0.04), than those patients, who had a recent
      follow-up examination before the onset of recurrence (n=14, median survival:
      22.3+ months). In the majority of recurrent cases with good prognosis, metastatic
      disease was confined to the regional lymph nodes and the presumptive diagnosis of
      metastatic disease was either made by palpation or by sonography of the regional
      lymph nodes. The observed drop-out rate of patients during the first 5 years of
      follow-up is substantial and does not depend on the patients' age, sex or on the
      tumour thickness. Although the frequency of recurrences among patients with thin
      melanomas is low, regular follow-up examinations including physical examination,
      as well as palpation and sonography of the regional lymph nodes, are essential.

PMID- 11506958
TI  - Effect of letrozole on the lipid profile in postmenopausal women with breast
      cancer.
AB  - Hormonal therapy plays a central role in the overall treatment of breast cancer.
      Aromatase inhibitors can inhibit the aromatase enzyme system resulting in a
      reduction of oestrogens. Letrozole is a non-steroidal aromatase inhibitor that
      effectively blocks aromatase activity without interfering with adrenal steroid
      biosynthesis. The drug can significantly reduce the levels of plasma oestrogens,
      which remain suppressed throughout the treatment. Data are scarce concerning the
      influence of these drugs on serum lipid levels. In the present study, we
      evaluated the effects of letrozole on the serum lipid profile in postmenopausal
      women with breast cancer. A total of 20 patients with breast cancer were treated
      with letrozole, 2.5 mg once daily. After an overnight fast, serum lipid
      parameters (total cholesterol, high density lipoprotein (HDL) cholesterol, low
      density lipoprotein (LDL) cholesterol, triglycerides, apolipoproteins A1, B and E
      and lipoprotein (a)) were measured before treatment and at 8 and 16 weeks
      afterwards. A significant increase in total cholesterol (P=0.05), LDL cholesterol
      (P<0.01) and apolipoprotein B levels (P=0.05) in the serum, as well as in the
      atherogenic risk ratios total cholesterol/HDL cholesterol (P<0.005) and LDL
      cholesterol/HDL cholesterol (P<0.005) was noticed after letrozole treatment. We
      conclude that letrozole administration in postmenopausal women with breast cancer
      has an unfavourable effect on the serum lipid profile.

PMID- 11506959
TI  - Cell biological factors in ductal carcinoma in situ (DCIS) of the breast
      relationship to ipsilateral local recurrence and histopathological
      characteristics.
AB  - All cases of ductal carcinoma in situ (DCIS) diagnosed from 1987 to 1991 in the
      Southern Health Care Region of Sweden, and operated upon with breast conserving
      treatment (BCT) with (n=66) or without (n=121) postoperative radiation (RT) were
      clinically followed, morphologically re-evaluated and analysed for cell
      biological factors (immunohistochemical assays or DNA flow cytometry). Median age
      at diagnosis was 58 years (range 29--83 years) and median follow-up was 62
      months. Oestrogen (ER)- and progesterone receptor (PR)-negativity, c-erbB-2
      overexpression, low bcl-2 expression, p53 accumulation, DNA non-diploidy and high
      Ki67, were strongly associated with high grade DCIS, and comedo-type necrosis. In
      contrast, significant associations to growth pattern (not diffuse versus diffuse)
      were seen only for c-erbB-2 and PgR. There was also a strong relationship between
      the cell biological factors, and a summary cell biological index based on
      principal component analysis was introduced (CBI-7). In the group that had not
      received postoperative RT, 31 ipsilateral local recurrences occurred (13
      invasive, 18 DCIS). Ipsilateral recurrence-free interval (IL-RFI) was in
      univariate analyses significantly, or almost significantly, shorter for patients
      showing p53 accumulation, high Ki67 or low bcl-2, compared with patients with
      normal p53, low Ki67 and high bcl-2. The prognostic importance of the remaining
      cell biological factors was less pronounced. On the other hand, the index CBI-7,
      was a strong predictor for recurrence.

PMID- 11506960
TI  - The adolescent with cancer.

PMID- 11506962
TI  - Mammographic findings and occupational exposure to pesticides currently in use on
      Crete.
AB  - This is a preliminary report of an outreach mammographic-screening programme on
      Crete. The screening is part of a study to test if occupational exposure to
      pesticides in greenhouses (mainly organophosphates and organocarbamates), may
      increase the risk of malignant or premalignant findings in mammographic
      examination. A total of 1062 women (aged 40--75 years) were recruited between
      1988 and 1993 and followed-up until 1998: 522 worked for at least 10 years in
      greenhouses for more than 4 h daily (exposed), and 540 never worked in
      agriculture (non-exposed). Statistics include detection rates and relative risks
      of mammographic findings. 'Exposed' women had a significantly (P<0.05) higher
      risk than 'non-exposed' for fibroadenoma, ductal hyperplasia, sclerotic adenosis,
      fibrohyperplastic disease, cystic disease and inflammatory mastitis. There were
      no significant differences in the detection rates of fibrocystic changes, lipoma
      and malignant changes or malignant tumours. Compared with older women (aged 50-
      75 years), younger women (aged 40--49 years), particularly in the 'exposed'
      group, had a higher detection rate of malignant tumours. These preliminary
      results indicate that 'exposed' women may have higher risks of incidence for a
      number of lesions, which are risk markers for subsequent invasive breast cancers.
      They confirm also that early screening for breast cancer is effective and
      provides an opportunity for a reduction in breast cancer mortality.

PMID- 11506963
TI  - Time trends in the results of breast conservation in 4694 women.
AB  - In a population-based cohort of 4694 women with invasive breast cancer, operated
      upon with breast conserving surgery (BCS) in 1981--1990 and followed through to
      1997, we studied how this technique had been adopted into clinical practice,
      especially with reference to the use of radiotherapy (RT). Our main aim was to
      see whether there was a drift in the risk of local recurrence and breast cancer
      death over time. During the 30,151 person-years of observation in the cohort,
      there were 582 local recurrences, 456 breast cancer deaths and 438 deaths due to
      other causes. Postoperative RT was given to 70.2%, but usage increased over the
      period. The women not receiving RT were mostly elderly, but also in women <70
      years, 20.4% did not receive RT. The risk for local recurrence after RT were 7.6
      and 17.8% at 5 and 10 years, respectively. Without RT, more than 30% had a local
      recurrence at 10 years. Thus, the choice not to irradiate failed to target women
      at a low risk. In a multivariate Cox analysis taking tumour size, nodal status,
      age at operation and RT into account, there was a trend for a higher risk of
      local recurrence in the later time period, relative hazard 1.5 (95% confidence
      interval (CI) 1.0--2.1). Corrected survival was 93.3 and 85.2% at 5 and 10 years,
      respectively.

PMID- 11506964
TI  - The relative importance of proliferation and cell death in breast cancer growth
      and response to tamoxifen.
AB  - Changes in tumour volume depend on the relative balance between cell
      proliferation and cell loss. However, these processes are not independent, and it
      remains unclear which is more important in tumour progression and regression. For
      example, the anti-oestrogen tamoxifen, a mainstay in the therapy of breast
      cancer, has both antiproliferative and pro-apoptotic actions, and their relative
      importance in clinical efficacy is unknown. Thus, using a model system based on
      oestrogen receptor (ER)-positive ZR-75-1 breast cancer xenografts, both increased
      apoptosis and reduced proliferation have been previously shown to occur within 7
      days of tamoxifen therapy (Cameron DA, Ritchie AA, Langdon S, Anderson TJ, Miller
      WR. Tamoxifen induced apoptosis in ZR-75 breast cancer xenografts antedates
      tumour regression. Breast Cancer Res Treat 1997, 45, 99--107). In the present
      study, Gompertzian growth curves have been fitted to individual breast cancer
      xenografts. This demonstrates that the growth rate of the untreated tumours is
      directly dependent only on the mitotic rate (P<0.001), whereas tumour response to
      tamoxifen correlates most strongly (P< 0.001) with the relative balance between
      apoptosis and mitosis, as evidenced by the apoptotic:mitotic ratio.

PMID- 11506965
TI  - Altered expression of several genes in highly metastatic subpopulations of a
      human pulmonary adenocarcinoma cell line.
AB  - Non-small cell lung cancer is associated with approximately 85% mortality due to
      its high metastatic potential. Therapeutic efforts have failed to produce a
      significant improvement in prognosis. In this situation, a better understanding
      of the key factors of metastasis may be useful for designing new molecular
      targets of therapy. In order to identify these factors, we compared the
      expression profiles of two subpopulations of an adenocarcinoma cell line with a
      high metastatic potential, PC9/f9 and PC9/f14, with the parent cell line, PC9,
      using a cDNA array. The expression of 15 genes was found to be significantly
      enhanced or reduced in the highly metastatic subpopulations. The expression of
      matrix metalloproteinase-2 (MMP-2), plasminogen activator inhibitor-1 (PAI-1) and
      interleukin-1 (IL-1 alpha) were upregulated in the highly metastatic
      subpopulations, while the expression of carcinoembryonic antigen (CEA), caspase
      5, Fas ligand, Prk/FNK, cyclin E, cyclin B1, Ki-67, proliferating cell nuclear
      antigen (PCNA), Smad4, macrophage proinflammatory human chemokine-3 alpha (MIP-3
      alpha)/LARC, Met and CD44 were downregulated. Data from the literature suggest
      that the altered expression of MMP-2, PAI-1, IL-1 alpha, CEA, caspase-5, Fas
      ligand, Prk/FNK and Smad4 promotes the highly metastatic phenotype. The
      differential expression of these genes was confirmed by Northern blot analysis,
      standard reverse transcription-polymerase chain reaction (RT-PCR) and real-time
      quantitative RT-PCR. This analysis in subpopulations of a lung cancer cell line
      indicated that the highly metastatic potential of lung cancer may be induced not
      by an alteration in the expression of a single gene, but by the accumulation of
      alterations in the expression of several genes involved in extracellular matrix
      (ECM) adhesion disruption, ECM degradation, escape from apoptosis, and resistance
      to transforming growth factor-beta(1) (TGF-beta(1)). Strategies for inhibiting
      metastasis of pulmonary adenocarcinoma should be designed accordingly.

PMID- 11506966
TI  - Hepatocyte growth factor (HGF) protects c-met-expressing Burkitt's lymphoma cell
      lines from apoptotic death induced by DNA damaging agents.
AB  - The relative sensitivity of neoplastic cells to DNA damaging agents is a key
      factor in cancer therapy. In this paper, we show that pretreatment of Burkitt's
      lymphoma cell lines expressing the c-met protooncogene with hepatocyte growth
      factor (HGF) protects them from death induced by DNA damaging agents commonly
      used in tumour therapy. This protection was observed in assays based on
      morphological assessment of apoptotic cells and DNA fragmentation assays. The
      protection was dose- and time-dependent -- maximal protection requiring pre
      incubation with 100 ng/ml HGF for 48 h. Western blotting analysis and flow
      cytometric studies revealed that HGF inhibited doxorubicin- and etoposide-induced
      decreases in the levels of the anti-apoptotic proteins Bcl-X(L), and to a lesser
      extent Bcl-2, without inducing changes in the pro-apoptotic Bax protein. Overall,
      these studies suggest that the accumulation of HGF within the microenvironment of
      neoplastic cells may contribute to the development of a chemoresistant phenotype.

PMID- 11506967
TI  - Inhibitors of cyclooxygenase-2 (COX-2) suppressed the proliferation and
      differentiation of human leukaemia cell lines.
AB  - Prostaglandins (PG) are known to play important roles in the proliferation and
      differentiation of leukaemia cells. The effect of the inhibitors of
      cyclooxygenase-2 (COX-2), a rate-limiting enzyme for the synthesis of PG, on the
      proliferation and differentiation of leukaemia cell lines was investigated. COX-2
      inhibitors, NS-398 and nabumetone, suppressed the proliferation of U-937 and ML-1
      cells by inducing a G0/G1 cell-cycle arrest. Cell-cycle arrest induced by these
      COX-2 inhibitors was not associated with an upregulation of the cyclin-dependent
      kinase inhibitors. COX-2 inhibitors also inhibited the differentiation of these
      cells induced by interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF
      alpha) and retinoic acid (RA). Treatment with NS-398 did not suppress the levels
      of PGs produced by these cells. Although COX-2 antisense oligonucleotide showed a
      similar inhibitory effect on these cells, its inhibitory effect was smaller than
      that of NS-398. These results suggest that COX-2 inhibitors may suppress the
      proliferation and differentiation of leukaemia cells both via COX-2-dependent and
      -independent pathways.

PMID- 11506968
TI  - Improvement of the quality of self assembled bilayer lipid membranes by using a
      negative potential.
AB  - Self-assembled lipid bilayer membranes (s-BLMs) on the tip of Teflon-coated
      silver electrodes were formed according to the T. Tien method. Their formation
      process and properties were investigated by capacitance and voltage current cycle
      measurements. The stability of the membranes was improved and defects were
      eliminated through the application of a negative dc potential during formation.
      Cyclic current-voltage measurements were applied to probe membrane integrity, by
      using an electrolyte interacting with the silver electrode. Oxidation and
      reduction peaks were observed for non defect-free membranes. These peaks were
      caused by oxidation of the silver electrode tip and their occurrence was a very
      sensitive means of measuring membrane integrity. The membrane was a barrier for
      the ion transport from the electrolyte solution to the electrode surface, and
      thus defect-free membranes inhibited the appearance of the peaks. With the s-BLMs
      produced by the described method, binding of ions and proteins to the membrane
      could be measured repetitively and reproducibly through changes in the system
      capacitance and the shape of the cyclovoltammogram. The presence of divalent ions
      lead to a specific increase in total system capacitance of membranes from charged
      lipids. Protein binding was measured as a decrease of the capacitance, in
      accordance with the thickness increase of the total membrane after binding. The
      facility of production and the sensitivity of the aforementioned substances could
      make the s-BLMs, produced by the described method, a valuable system to be
      developed in the field of biosensing.

PMID- 11506969
TI  - Cation selective ion channels formed by macrodiolide antibiotic elaiophylin in
      lipid bilayer membranes.
AB  - The macrodiolide antibiotic elaiophylin (1) forms stable, long-lasting cation
      selective ion channels in planar lipid bilayer membranes prepared from soybean
      phosphatidylcholine. Current of the single ion channel displayed two sublevels
      corresponding to the two substates of the channel conductance: a slow substate,
      with about 5 s of mean dwell time in the open state at 40% level of the total
      amplitude conductance, and a fast substate of higher conductance with dwell times
      in the open and closed state of about 0.1 s. Amplitude conductances of the single
      ion channels in 200 mM of LiCl, NaCl, KCl, RbCl and CsCl were 75, 140, 220, 240
      and 226 pS, and the conductance was linear function of the electrolyte
      concentration. Ratios of cation to anion permeabilities of the channel for NaCl
      and KCl were 8+/-2 and >24, respectively. A molecular model of the channel
      structure is suggested.

PMID- 11506970
TI  - An electrochemical multienzymatic biosensor for determination of cholesterol.
AB  - This paper describes an electrochemical biosensor for free cholesterol
      monitoring. The sensor is a multienzymatic electrodic system in which horseradish
      peroxidase and cholesterol oxidase are simultaneously immobilized within a
      polymeric film, on the surface of a pyrolitic graphite electrode. From
      voltammetric and amperometric (flow-injection) data obtained, the efficiency,
      reproducibility and stability of the system are discussed. Results obtained, of
      interest for basic and applied biochemistry, represent a first step for
      construction of a mediator-free biosensor with potentialities for a successful
      application in the biosensor area.

PMID- 11506971
TI  - A comprehensive approach to electro-orientation, electrodeformation,
      dielectrophoresis, and electrorotation of ellipsoidal particles and biological
      cells.
AB  - Suspended cells may respond to AC polarization by orienting, deforming, moving or
      rotating. For modeling of ellipsoidal cells, a new dipole approach is proposed.
      Along each of the principal axis of the model, three finite elements of arbitrary
      but equal cross-sectional area for the interior, low conductive membrane shell
      and exterior are assumed. The length of the external medium elements is defined
      by influential radii which are related to the depolarizing factors. The model
      predicts the potential at the ellipsoid's surface leading to the induced dipole
      moment. The moment obtained is identical to the Laplace approach for homogeneous
      ellipsoids; in the single-shell case, it is slightly different. The reason is the
      constant shell thickness which overcomes the confocal thickness necessary for the
      Laplace solution. Expressions for electro-orientation, deformation,
      dielectrophoresis, and electrorotation are derived. In linearly and circularly
      polarized fields, different orientation spectra are predicted to occur. While in
      linearly polarized AC fields, particles are oriented along their axis of highest
      polarizability, in circularly polarized fields, the axis of lowest polarizability
      is oriented perpendicular to the plane of field rotation. Based on this finding,
      a new electro-orientation method is proposed. In dielectrophoresis and
      electrorotation, reorientations are predicted which lead to discontinuous
      spectra.

PMID- 11506972
TI  - Dielectrophoretic manipulation of a single chlorella cell with dual-microdisk
      electrode.
AB  - Dielectrophoretic manipulation of a single chlorella cell was performed using a
      dual-microdisk electrode, which consists of two Pt-Rh ultrafine wires (ca. 1
      microm radius) sealed in a glass capillary. An attractive or repulsive force was
      induced on the chlorella depending on the frequency of the ac voltage applied
      between the two disk electrodes. To avoid the direct contact of a chlorella with
      the metal, a dual electrode with retracted disks was fabricated and used for
      forming a micropattern of chlorellas at a solid substrate. The effect of both the
      frequency and ion concentration of the solutions on the dielectrophoretic force
      exerted on a chlorella cell was investigated in detail based on the theories of
      dielectrophoresis.

PMID- 11506973
TI  - Real-time monitoring of brain energy metabolism in vivo using
      microelectrochemical sensors: the effects of anesthesia.
AB  - Rats were implanted in the striatum with a Pt/Ir electrode for measurement of
      regional cerebral blood flow (rCBF) (H(2) clearance technique), a carbon paste
      electrode for monitoring tissue oxygen and a glucose biosensor for monitoring
      extracellular glucose. Changes in all three parameters were recorded in response
      to the intraperitoneal (i.p.) administration of the anesthetics chloral hydrate
      (350 mg/kg), sodium pentobarbitone (60 mg/kg) and ketamine (200 mg/kg). An i.p.
      injection of normal saline, given as a control for the injection of the
      anesthetics, produced a parallel increase in rCBF and tissue oxygen accompanied
      by a brief decrease in extracellular glucose. Changes in tissue oxygen reflected
      the changes in rCBF; there was a decrease in both after sodium pentobarbitone, a
      decrease followed by a rebound after ketamine and a transient increase after
      chloral hydrate. All three anesthetics produced a decrease in extracellular
      glucose. The disparity between the changes in glucose and the changes in rCBF and
      oxygen suggests that during anesthesia, the reduction in extracellular glucose is
      not due to a reduction in the direct delivery of glucose from the blood vascular
      system. These results also indicate that levels of enzymatic substrates and
      mediators, which are intrinsic to the design and operation of amperometric
      biosensors, are clearly altered in a complex manner by anesthesia and suggest
      that caution should be exercised in extrapolating data from acute anesthetized
      experiments to normal physiology.

PMID- 11506974
TI  - Effect of dimethyl sulfoxide on the electron transfer reactivity of hemoglobin.
AB  - Hemoglobin, after being treated with dimethyl sulfoxide, exhibits a direct
      electrochemical response at a pyrolytic graphite electrode. The apparent standard
      potential (E degrees ') of hemoglobin is -0.119 V (vs. NHE). Meanwhile, since no
      electrochemical mediator is required for its direct electrochemistry, this work
      provides a convenient way to perform electrochemical research on this protein.

PMID- 11506975
TI  - Reduction of the contribution of electrode polarization effects in the radiowave
      dielectric measurements of highly conductive biological cell suspensions.
AB  - Electrode polarization effects in dielectric spectra of highly conductive
      biological cell suspensions cause a severe difficulty in the estimation of
      dielectric parameters of cells under physiological conditions. This problem
      becomes particularly serious with the increase of the electrical conductivity of
      the sample, preventing the use of low frequencies in the characterization of
      biological systems, especially aqueous biological systems. Although a variety of
      methods to correct the electrode polarization have been proposed in the past, no
      simple technique for its correction has been available so far. Since the
      magnitude of the polarization effect can be time-dependent owing to changes in
      the conductance of the suspending medium or to possible alteration in the
      electrode surface structure, it is clear that correction procedure should be
      based on a kind of "self-correction" method, avoiding the so-called "comparison
      methods" which, on the contrary, require time-independent effects. This note is
      aimed to address this problem considering an electrode polarization modelled by a
      constant phase angle (CPA) element in series with the sample admittance. A
      scaling-law frequency dependence has found to describe the a.c. response of the
      interface between the electrode and the bulk electrolyte solution. Although this
      approach has been extensively proposed in the past in the analysis of dielectric
      spectra of biological suspensions, we have somewhat modified the way it has been
      previously applied and have re-examined in detail its effectiveness in typical
      systems of biological interest. The results give support to the proposed
      analysis, allowing the complete low-frequency dielectric spectra characterization
      at frequencies of the order of 1 kHz for samples with a bulk ionic conductivity
      as large as that of the order of 1 mho/m. Typical examples with different
      dielectric behaviours are extensively discussed in order to show the
      applicability of the proposed method to biological samples.

PMID- 11506976
TI  - Estimates of the intramembrane field through the harmonics of capacitive current
      in inhomogeneous bilayer lipid membranes.
AB  - Intramembrane field gives information about localisation of fixed charges or
      dipoles inside the lipid bilayer. There is systematic discrepancy between field
      estimates made by various methods. The possible reason of this discrepancy can be
      attributed to the misinterpretation of the data in the frames of the methods
      used. It stands for the method that is based on the compensation of the 2nd
      harmonic of capacitive current generated due to electrostriction phenomenon if
      sine voltage is applied to the bilayer. The theoretical grounds of the method
      mentioned are oversimplified because membrane heterogeneity has not been taken
      into consideration. The purpose of the work is the analysis of the generation of
      harmonics of capacitive current in inhomogeneous bilayer if intramembrane charges
      are located at different depth. The results of the study enable one to determine
      the position of intramembrane charges. The theoretical methods are used. The
      bilayer electrostriction induced by the electric field in the presence of
      intramembrane charges is computed. The intramembrane field depends upon
      localisation of the charges inside the bilayer like a sine curve; it goes to zero
      if the charges are located in the centre of the membrane. The charge discreteness
      affects the value of the compensation voltage due to nonlinearity of the bilayer
      deformations close to the charge. The probable appendices of outcomes are
      discussed for problems of intramembrane dye localisation and ion transport in the
      channel of sodium/potassium ATPase.

PMID- 11506977
TI  - Direct electrochemistry and electrocatalysis with horseradish peroxidase in
      Eastman AQ films.
AB  - Stable films made from ionomer poly(ester sulfonic acid) or Eastman AQ29 on
      pyrolytic graphite (PG) electrodes gave direct electrochemistry for incorporated
      enzyme horseradish peroxidase (HRP). Cyclic voltammetry of HRP-AQ films showed a
      pair of well-defined, nearly reversible peaks at about -0.33 V vs. SCE at pH 7.0
      in blank buffers, characteristic of HRP heme Fe(III)/Fe(II) redox couple. The
      electron transfer between HRP and PG electrode was greatly facilitated in AQ
      films. The electrochemical parameters such as apparent heterogeneous electron
      transfer rate constant (k(s)) and formal potential (E(o')) were estimated by
      fitting the data of square-wave voltammetry (SWV) with nonlinear regression
      analysis. Reflectance absorption infrared (RAIR) and UV-Vis absorption spectra
      demonstrated that HRP retained a near native conformation in AQ films. The
      embedded HRP in AQ films retained the electrocatalytic activity for oxygen,
      nitrite and hydrogen peroxide. Possible mechanism of catalytic reduction of
      H(2)O(2) with HRP-AQ films was proposed.

PMID- 11506978
TI  - Cell membrane electropermeabilization by symmetrical bipolar rectangular pulses.
      Part I. Increased efficiency of permeabilization.
AB  - The paper presents a comparative study of electropermeabilization of cells in
      suspension by unipolar and symmetrical bipolar rectangular electric pulses. While
      the parameters of electropermeabilization by unipolar pulses have been
      investigated extensively both in cell suspensions and in tissues, studies using
      bipolar pulses have been rare, partly due to the lack of commercially available
      bipolar pulse generators with pulse parameters suitable for
      electropermeabilization. We have developed a high-frequency amplifier and coupled
      it to a function generator to deliver high-voltage pulses of programmable shapes.
      With symmetrical bipolar pulses, the pulse amplitude required for the
      permeabilization of 50% of the cells was found to be approximately 20% lower than
      with unipolar pulses, while no statistically significant difference was detected
      between the pulse amplitudes causing the death of 50% of the cells. Bipolar
      pulses also led to more than 20% increase in the uptake of lucifer yellow. We
      show that these results have a theoretical background, because bipolar pulses (i)
      counterbalance the asymmetry of the permeabilized areas at the poles of the cell
      which is introduced by the resting transmembrane voltage, and (ii) increase the
      odds of permeabilization of cells having a nonspherical shape or a nonhomogeneous
      membrane. If similar results are also obtained in tissues, bipolar pulse
      generators could in due course gain a wide, or even a predominant use in cell
      membrane electropermeabilization.

PMID- 11506979
TI  - Cell membrane electropermeabilization by symmetrical bipolar rectangular pulses.
      Part II. Reduced electrolytic contamination.
AB  - The paper presents a comparative study of the contamination of a cell suspension
      by ions released from aluminum cuvettes (Al(3+)) and stainless steel electrodes
      (Fe(2+)/Fe(3+)) during cell membrane electropermeabilization by unipolar and by
      symmetrical bipolar rectangular electric pulses. A single pulse and a train of
      eight pulses were delivered to electrodes at a 2-mm distance, with 100-micros and
      1-ms pulse durations, and amplitudes ranging from 0 to 400 V for unipolar, and
      from 0 to 280 V for bipolar pulses. We found that the released concentrations of
      Al(3+) and Fe(2+)/Fe(3+) were always more than one order of magnitude lower with
      bipolar pulses than with unipolar pulses of the same amplitude and duration. We
      then investigated the viability of DC-3F cells after 1 h of incubation in the
      medium containing different concentrations of Al(3+) or Fe(2+)/Fe(3+) within the
      range of measured released concentrations (up to 2.5 mM for both ions), thus
      separating the effects of electrolytic contamination from the effects of
      electropermeabilization itself. For Fe(2+)/Fe(3+), loss of cell viability became
      significant at concentrations above 1.5 mM, while for Al(3+), no effect on cell
      survival was detected within the investigated range. Still, reports on the
      biochemical effects of released Al(3+) also suggest that with aluminum cuvettes,
      electrolytic contamination can be detrimental. Our study shows that electrolytic
      contamination and its detrimental effects can be largely reduced with no loss in
      efficiency of electropermeabilization, if bipolar rectangular pulses of the same
      amplitude and duration are used instead of the commonly applied unipolar pulses.

PMID- 11506980
TI  - Influence of bromide on electrochemistry of photosynthetic reaction center films
      on gold electrodes.
AB  - A strong influence of bromide ion was found on voltammetry of layered films of
      photosynthetic reaction center (RC) protein and polyions on gold electrodes.
      Similar, but not identical, cyclic voltammetry peaks were observed for polyion
      films on gold with and without RC when the buffer solutions contained bromide
      ion. CVs of RC films were quite different in the absence of bromide. These new
      findings suggest that previously published results were biased by significant
      background peaks involving bromide ion adsorption/desorption.

PMID- 11506981
TI  - Differential control of sympathetic outflow.
AB  - With advances in experimental techniques, the early views of the sympathetic
      nervous system as a monolithic effector activated globally in situations
      requiring a rapid and aggressive response to life-threatening danger have been
      eclipsed by an organizational model featuring an extensive array of functionally
      specific output channels that can be simultaneously activated or inhibited in
      combinations that result in the patterns of autonomic activity supporting
      behavior and mediating homeostatic reflexes. With this perspective, the defense
      response is but one of the many activational states of the central autonomic
      network. This review summarizes evidence for the existence of tissue-specific
      sympathetic output pathways, which are likely to include distinct populations of
      premotor neurons whose target specificity could be assessed using the functional
      fingerprints developed from characterizations of postganglionic efferents to
      known targets. The differential responses in sympathetic outflows to stimulation
      of reflex inputs suggest that the circuits regulating the activity of sympathetic
      premotor neurons must have parallel access to groups of premotor neurons
      controlling different functions but that these connections vary in their ability
      to influence different sympathetic outputs. Understanding the structural and
      physiological substrates antecedent to premotor neurons that mediate the
      differential control of sympathetic outflows, including those to
      noncardiovascular targets, represents a challenge to our current technical and
      analytic approaches.

PMID- 11506982
TI  - Overexpression of sarcolemmal calcium pump attenuates induction of cardiac gene
      expression in response to ET-1.
AB  - The function of the plasma membrane calmodulin-dependent calcium ATPase (PMCA) in
      myocardium is unknown. PMCA is localized in caveolae, 50- to 100-nm membrane
      invaginations, which also contain receptors for endothelin-1 (ET-1) and various
      other ligands. PMCA has been suggested to play a role in regulation of caveolar
      signal transduction. We studied the effects of the hypertrophic agonist ET-1 and
      increased coronary perfusion pressure on cardiac synthesis of B-type natriuretic
      peptide (BNP) in transgenic rats overexpressing the human PMCA 4CI in isolated
      perfused heart preparation. ET-1 infusion for 2 h increased BNP mRNA levels
      twofold in left ventricles (LV) of nontransgenic rats, whereas no increase was
      noted in PMCA rat hearts. Similar responses were seen in adrenomedullin and c-fos
      mRNA levels, and in immunoreactive BNP secretion. Increased mechanical load
      produced by elevated perfusion pressure induced similar 1.5- to 1.6-fold
      increases in LV BNP mRNA in both nontransgenic and PMCA rat hearts. These results
      show that cardiac overexpression of PMCA attenuates ET-1-stimulated early
      induction of cardiac gene expression, suggesting that PMCA may modulate
      myocardial growth responses.

PMID- 11506983
TI  - Temperature-sensitive properties of rat suprachiasmatic nucleus neurons.
AB  - The hypothalamic suprachiasmatic nucleus (SCN) contains a heterogeneous
      population of neurons, some of which are temperature sensitive in their firing
      rate activity. Neuronal thermosensitivity may provide cues that synchronize the
      circadian clock. In addition, through synaptic inhibition on nearby cells,
      thermosensitive neurons may provide temperature compensation to other SCN
      neurons, enabling postsynaptic neurons to maintain a constant firing rate despite
      changes in temperature. To identify mechanisms of neuronal thermosensitivity,
      whole cell patch recordings monitored resting and transient potentials of SCN
      neurons in rat hypothalamic tissue slices during changes in temperature. Firing
      rate temperature sensitivity is not due to thermally dependent changes in the
      resting membrane potential, action potential threshold, or amplitude of the fast
      afterhyperpolarizing potential (AHP). The primary mechanism of neuronal
      thermosensitivity resides in the depolarizing prepotential, which is the slow
      depolarization that occurs prior to the membrane potential reaching threshold. In
      thermosensitive neurons, warming increases the prepotential's rate of
      depolarization, such that threshold is reached sooner. This shortens the
      interspike interval and increases the firing rate. In some SCN neurons, the slow
      component of the AHP provides an additional mechanism for thermosensitivity. In
      these neurons, warming causes the slow AHP to begin at a more depolarized level,
      and this, in turn, shortens the interspike interval to increase firing rate.

PMID- 11506984
TI  - Predicting cerebral blood flow response to orthostatic stress from resting
      dynamics: effects of healthy aging.
AB  - The transfer function relating arterial pressure (AP) to cerebral blood flow
      velocity (CBFV) during resting conditions has been used to predict the CBFV
      response to hypotension. We hypothesized that this approach could predict the
      CBFV response to posture change in elderly individuals if impaired autoregulation
      allowed changes in AP to be passively transferred to CBFV. AP (Finapres) and CBFV
      (middle cerebral artery transcranial Doppler) were measured in 10 healthy young
      (age 24 +/- 1 yr) and 10 healthy elderly (age 72 +/- 3 yr) subjects during 5 min
      of quiet sitting and 1 min of active standing while breathing was paced at 0.25
      Hz. Transfer functions between AP and CBFV changes during sitting were estimated
      from each full waveform in both low-frequency (LF; 0.05-0.2 Hz) and heartbeat
      frequency (HBF; 0.7-1.4 Hz) ranges. The impulse-response function was used to
      compute changes in CBFV during posture change. The LF transfer function did not
      predict orthostatic changes in CBFV in either group, suggesting normal cerebral
      autoregulation. In the HBF range, the prediction was high in elderly (R = 0.65 +/
      0.23) but not young subjects (R = 0.19 +/- 0.35; P < 0.003, young vs. elderly).
      Thus rapidly acting regulatory mechanisms that reduce the transmission of beat-to
      beat changes in AP to CBFV may be engaged during posture change in young but not
      elderly subjects.

PMID- 11506985
TI  - Circulating angiotensin II mediates sodium appetite in adrenalectomized rats.
AB  - We investigated the role of circulating ANG II in sodium appetite after
      adrenalectomy. Adrenalectomized rats deprived of their main access to sodium (0.3
      M NaCl) for 9 h drank 14.1 +/- 1.5 ml of the concentrated saline solution in 2 h
      of access. Intravenous infusion of captopril (2.5 mg/h) during the last 5 h of
      sodium restriction reduced sodium intake by 77 +/- 12% (n = 5) without affecting
      the degree of sodium depletion and hypovolemia incurred during deprivation.
      Functional evidence indicates that this dose of captopril blocked production of
      ANG II in the peripheral circulation, but not in the brain; that is, injection of
      ANG I into the lateral brain ventricle stimulated intake of both water and 0.3 M
      NaCl. Intravenous infusion of ANG II (starting 10-15 min before 0.3 M NaCl became
      available) in adrenalectomized, captopril-treated rats restored both sodium
      intake and blood pressure to values seen in rats not treated with captopril.
      Longer (20 h) infusions of captopril in 22-h sodium-restricted rats also blocked
      sodium appetite, but reduced or prevented sodium depletion. Intravenous infusion
      of ANG II after these long captopril infusions stimulated sodium intake, but
      intake was less than in controls not treated with captopril. These results
      indicate that most or all of the sodium appetite of adrenalectomized rats is
      mediated by circulating ANG II.

PMID- 11506986
TI  - N-acetyl-L-cysteine improves renal medullary hypoperfusion in acute renal
      failure.
AB  - This study evaluated the effects of N-acetyl-L-cysteine (NAC), a free radical
      scavenger, and N(omega)-nitro-L-arginine methyl ester (L-NAME), a nitric oxide
      (NO) synthesis inhibitor, on the changes in renal function, intrarenal blood flow
      distribution (laser-Doppler flowmetry), and plasma peroxynitrite levels during
      the acute renal failure (ARF) produced by inferior vena cava occlusion (IVCO; 45
      min) in anesthetized rats. Renal blood flow fell on reperfusion (whole kidney by 
      45.7%; cortex -58.7%, outer medulla -62.8%, and papilla -47.7%); glomerular
      filtration rate (GRF) also decreased (-68.6%), whereas fractional sodium
      excretion (FE(Na%)) and peroxynitrite and NO/NO plasma levels increased (189.5,
      46.5, and 390%, respectively) after ischemia. Pretreatment with L-NAME (10
      microg. kg(-1). min(-1)) aggravated the fall in renal blood flow seen during
      reperfusion (-60%). Pretreatment with NAC (150 mg/kg bolus + 715 microg. kg(-1).
      min(-1) iv) partially prevented those changes in renal function (GFR only fell by
      -29.2%, and FE(Na%) increased 119.4%) and laser-Doppler blood flow, especially in
      the outer medulla, where blood flow recovered to near control levels during
      reperfusion. These beneficial effects seen in rats given NAC seem to be dependent
      on the presence of NO, because they were abolished in rats pretreated with L
      NAME. Also, the antioxidant effects of NAC prevented the increase in plasma
      peroxynitrite after ischemia. In conclusion, NAC ameliorates the renal failure
      and the outer medullary vasoconstriction induced by ICVO, effects that seem to be
      dependent on the presence of NO and the scavenging of peroxynitrite.

PMID- 11506987
TI  - Estradiol treatment increases feeding-induced c-Fos expression in the brains of
      ovariectomized rats.
AB  - The steroid hormone estradiol decreases meal size by increasing the potency of
      negative-feedback signals involved in meal termination. We used c-Fos
      immunohistochemistry, a marker of neuronal activation, to investigate the
      hypothesis that estradiol modulates the processing of feeding-induced negative
      feedback signals within the nucleus of the solitary tract (NTS), the first
      central relay of the neuronal network controlling food intake, and within other
      brain regions related to the control of food intake. Chow-fed, ovariectomized
      rats were injected subcutaneously with 10 microg 17-beta estradiol benzoate or
      sesame oil vehicle on 2 consecutive days. Forty-eight hours after the second
      injections, 0, 5, or 10 ml of a familiar sweet milk diet were presented for 20
      min at dark onset. Rats were perfused 100 min later, and brain tissue was
      collected and processed for c-Fos-like immunoreactivity. Feeding increased the
      number of c-Fos-positive cells in the NTS, the paraventricular nucleus of the
      hypothalamus (PVN), and the central nucleus of the amygdala (CeA) in oil-treated
      rats. Estradiol treatment further increased this response in the caudal,
      subpostremal, and intermediate NTS, which process negative-feedback satiation
      signals, but not in the rostral NTS, which processes positive-feedback gustatory
      signals controlling meal size. Estradiol treatment also increased feeding-induced
      c-Fos in the PVN and CeA. These results indicate that modest amounts of food
      increase neuronal activity within brain regions implicated in the control of meal
      size in ovariectomized rats and that estradiol treatment selectively increases
      this activation. They also suggest that estradiol decreases meal size by
      increasing feeding-related neuronal activity in multiple regions of the
      distributed neural network controlling meal size.

PMID- 11506988
TI  - Evidence that hemorrhagic hypotension is mediated by the ventrolateral
      periaqueductal gray region.
AB  - Severe hemorrhage lowers arterial pressure by suppressing sympathetic activity.
      This study tested the hypothesis that the decompensatory phase of hemorrhage is
      mediated by the ventrolateral periaqueductal gray (vlPAG), a region importantly
      involved in the autonomic and behavioral responses to stress and trauma. Neuronal
      activity in the vlPAG was inhibited with either lidocaine or cobalt chloride 5
      min before hemorrhage (2.5 ml/100 g body wt) was initiated in conscious,
      unrestrained rats. Bilateral injection of lidocaine (0.5 microl of a 2% or 1
      microl of a 5% solution) into the caudal vlPAG delayed the onset and reduced the
      magnitude of the hypotension produced by hemorrhage significantly. In contrast,
      inactivation of the dorsolateral PAG with lidocaine was ineffective. Cobalt
      chloride (5 mM; 0.5 microl), which inhibits synaptic transmission but not axonal
      conductance, also attenuated hemorrhagic hypotension significantly.
      Microinjection of lidocaine or cobalt chloride into the vlPAG of normotensive,
      nonhemorrhaged rats did not influence cardiovascular function. These data
      indicate that the vlPAG plays an important role in the response to hemorrhage.

PMID- 11506989
TI  - Effect of leptin on intestinal apolipoprotein AIV in response to lipid feeding.
AB  - We determined apolipoprotein AIV (apo AIV) content in intestinal epithelial cells
      using immunohistochemistry when leptin was administered intravenously. Most of
      the apo AIV immunoreactivity in the untreated intestine was located in the
      villous cells as opposed to the crypt cells. Regional distribution of apo AIV
      immunostaining revealed low apo AIV content in the duodenum and high content in
      the jejunum that gradually decreases caudally toward the ileum. Intraduodenal
      infusion of lipid (4 h) significantly increased apo AIV immunoreactivity in the
      jejunum and ileum. Simultaneous intravenous leptin infusion plus duodenal lipid
      infusion markedly suppressed apo AIV immunoreactivity. Duodenal lipid infusion
      increased plasma apo AIV significantly (measured by ELISA), whereas simultaneous
      leptin infusion attenuated the increase. These findings suggest that leptin may
      regulate circulating apo AIV by suppressing apo AIV synthesis in the small
      intestine.

PMID- 11506990
TI  - Postexercise fat intake repletes intramyocellular lipids but no faster in trained
      than in sedentary subjects.
AB  - The hypotheses that postexercise replenishment of intramyocellular lipids (IMCL)
      is enhanced by endurance training and that it depends on fat intake were tested.
      Trained and untrained subjects exercised on a treadmill for 2 h at 50% peak
      oxygen consumption, reducing IMCL by 26-22%. During recovery, they were fed 55%
      (high fat) or 15% (low fat) lipid energy diets. Muscle substrate stores were
      estimated by (1)H (IMCL)- and (13)C (glycogen)-magnetic resonance spectroscopy in
      tibialis anterior muscle before and after exercise. Resting IMCL content was 71%
      higher in trained than untrained subjects and correlated significantly with
      glycogen content. Both correlated positively with indexes of insulin sensitivity.
      After 30 h on the high-fat diet, IMCL concentration was 30-45% higher than
      preexercise, whereas it remained 5-17% lower on the low-fat diet. Training status
      had no significant influence on IMCL replenishment. Glycogen was restored within
      a day with both diets. We conclude that fat intake postexercise strongly promotes
      IMCL repletion independently of training status. Furthermore, replenishment of
      IMCL can be completed within a day when fat intake is sufficient.

PMID- 11506991
TI  - Dexamethasone and epinephrine stimulate surfactant secretion in type II cells of
      embryonic chickens.
AB  - Pulmonary surfactant (PS), a mixture of phospholipids and proteins secreted by
      alveolar type II cells, functions to reduce the surface tension in the lungs of
      all air-breathing vertebrates. Here we examine the control of PS during lung
      development in a homeothermic egg-laying vertebrate. In mammals, glucocorticoids
      and autonomic neurotransmitters contribute to the maturation of the surfactant
      system. We examined whether dexamethasone, epinephrine, and carbamylcholine
      hydrochloride (agonist for acetylcholine) increased the amount of PS secreted
      from cultured type II cells of the developing chicken lung. In particular, we
      wanted to establish whether dexamethasone would increase PS secretion through a
      process involving lung fibroblasts. We isolated and cocultured type II cells and
      lung fibroblasts from chickens after 16, 18, and 20 days of incubation and from
      hatchlings (day 21). Epinephrine stimulated phosphatidylcholine (PC) secretion at
      all stages, whereas dexamethasone stimulated secretion of PC at days 16 and 18.
      Carbamylcholine hydrochloride had no effect at any stage. This is the first study
      to establish the existence of similar cellular pathways regulating the
      development of surfactant in chickens and eutherian mammals, despite the vastly
      different birthing strategies and lung structure and function.

PMID- 11506992
TI  - Effects of lower body positive pressure on muscle sympathetic nerve activity
      response to head-up tilt.
AB  - The present study was performed to test the hypothesis that application of lower
      body positive pressure (LBPP) during orthostasis would reduce the baroreflex
      mediated enhancement in sympathetic activity in humans. Eight healthy young men
      were exposed to a 70 degrees head-up tilt (HUT) on application of 30 mmHg LBPP.
      Muscle sympathetic nerve activity (MSNA) was microneurographically recorded from
      the tibial nerve, along with hemodynamic variables. We found that in the supine
      position with LBPP, MSNA remained unchanged (13.4 +/- 3.3 vs. 11.8 +/- 2.3
      bursts/min, without vs. with LBPP; P > 0.05), mean arterial pressure was
      elevated, but arterial pulse pressure and heart rate did not alter. At 70 degrees
      HUT with LBPP, the enhanced MSNA response was reduced (33.8 +/- 5.0 vs. 22.5 +/-
      2.2 bursts/min, without vs. with LBPP; P < 0.05), mean arterial pressure was
      higher, the decreased pulse pressure was restored, and the increased heart rate
      was attenuated. We conclude that the baroreflex-mediated enhancement in
      sympathetic activity during HUT was reduced by LBPP. Application of LBPP in HUT
      induced an obvious cephalad fluid shift as well as a restoration of arterial
      pulse pressure, which reduced the inhibition of the baroreceptors. However, the
      activation of the intramuscular mechanoreflexes produced by 30 mmHg LBPP might
      counteract the effects of baroreflexes.

PMID- 11506993
TI  - Altered hormone levels and circadian rhythm of activity in the WKY rat, a
      putative animal model of depression.
AB  - The Wistar Kyoto (WKY) rat is hyperreactive to stress and exhibits depressive
      like behavior in several standard behavioral tests. Because patients with
      depressive disorders often exhibit disruptions in the circadian rhythm of
      activity, as well as altered secretory patterns of the hypothalamic-pituitary
      adrenal and hypothalamic-pituitary-thyroid hormones, we tested the hypothesis
      that these phenomena occur in the WKY rat. Plasma ACTH and corticosterone levels
      remained significantly higher after the diurnal peak for several hours in WKY
      rats relative to Wistar rats. Also, plasma levels of thyroid-stimulating hormone
      were significantly higher in WKY relative to Wistar rats across the 24-h period,
      despite normal or slightly higher levels of 3,5,3'-triiodothyronine. In addition,
      under constant darkness conditions, WKY rats exhibited a shorter free running
      period and a decreased response to a phase-delaying light pulse compared with
      Wistar rats. In several ways these results are similar to those seen in other
      animal models of depression as well as in depressed humans, suggesting that the
      WKY rat could be used to investigate the genetic basis for these abnormalities.

PMID- 11506994
TI  - Hyperglycemia modulates angiotensinogen gene expression.
AB  - Elevated plasma angiotensinogen (AGT) levels have been demonstrated in insulin
      resistant states such as obesity and type 2 diabetes mellitus (DM2), conditions
      that are directly correlated to hypertension. We examined whether
      hyperinsulinemia or hyperglycemia may modulate fat and liver AGT gene expression
      and whether obesity and insulin resistance are associated with abnormal AGT
      regulation. In addition, because the hexosamine biosynthetic pathway is
      considered to function as a biochemical sensor of intracellular nutrient
      availability, we hypothesized that activation of this pathway would acutely
      mediate in vivo the induction of AGT gene expression in fat and liver. We studied
      chronically catheterized lean (approximately 300 g) and obese (approximately 450
      g) Sprague-Dawley rats in four clamp studies (n = 3/group), creating
      physiological hyperinsulinemia (approximately 60 microU/ml, by an insulin clamp),
      hyperglycemia (approximately 18 mM, by a pancreatic clamp using somatostatin to
      prevent endogenous insulin secretion), or euglycemia with glucosamine infusion
      (GlcN; 30 micromol. kg(-1). min(-1)) and equivalent saline infusions (as a
      control). Although insulin infusion suppressed AGT gene expression in fat and
      liver of lean rats, the obese rats demonstrated resistance to this effect of
      insulin. In contrast, hyperglycemia at basal insulin levels activated AGT gene
      expression in fat and liver by approximately threefold in both lean and obese
      rats (P < 0.001). Finally, GlcN infusion simulated the effects of hyperglycemia
      on fat and liver AGT gene expression (2-fold increase, P < 0.001). Our results
      support the hypothesis that physiological nutrient "pulses" may acutely induce
      AGT gene expression in both adipose tissue and liver through the activation of
      the hexosamine biosynthetic pathway. Resistance to the suppressive effect of
      insulin on AGT expression in obese rats may potentiate the effect of nutrients on
      AGT gene expression. We propose that increased AGT gene expression and possibly
      its production may provide another link between obesity/insulin resistance and
      hypertension.

PMID- 11506995
TI  - Volume-activated trimethylamine oxide efflux in red blood cells of spiny dogfish
      (Squalus acanthias).
AB  - The aims of this study were to determine the pathway of swelling-activated
      trimethylamine oxide (TMAO) efflux and its regulation in spiny dogfish (Squalus
      acanthias) red blood cells and compare the characteristics of this efflux pathway
      with the volume-activated osmolyte (taurine) channel present in erythrocytes of
      fishes. The characteristics of the TMAO efflux pathway were similar to those of
      the taurine efflux pathway. The swelling-activated effluxes of both TMAO and
      taurine were significantly inhibited by known anion transport inhibitors (DIDS
      and niflumic acid) and by the general channel inhibitor quinine. Volume expansion
      by hypotonicity, ethylene glycol, and diethyl urea activated both TMAO and
      taurine effluxes similarly. Volume expansion by hypotonicity, ethylene glycol,
      and diethyl urea also stimulated the activity of tyrosine kinases p72syk and
      p56lyn, although the stimulations by the latter two treatments were less than by
      hypotonicity. The volume activations of both TMAO and taurine effluxes were
      inhibited by tyrosine kinase inhibitors, suggesting that activation of tyrosine
      kinases may play a role in activating the osmolyte effluxes. These results
      indicate that the volume-activated TMAO efflux occurs via the organic osmolyte
      (taurine) channel and may be regulated by the volume activation of tyrosine
      kinases.

PMID- 11506996
TI  - Effect of cortisol on the physiology of cultured pavement cell epithelia from
      freshwater trout gills.
AB  - Cortisol had dose-dependent effects on the electrophysiological, permeability,
      and ion-transporting properties of cultured pavement cell epithelia derived from
      freshwater rainbow trout gills and grown on cell culture filter supports. Under
      both symmetrical (L15 media apical/L15 media basolateral) and asymmetrical
      (freshwater apical/L15 media basolateral) culture conditions, cortisol treatment
      elevated transepithelial resistance, whereas permeability of epithelia to a
      paracellular permeability marker (polyethylene glycol-4000) decreased. Cortisol
      did not alter the Na(+)-K(+)-ATPase activity or the total protein content of the
      cultured preparations. During 24-h exposure to asymmetrical conditions, the net
      loss rates of both Na(+) and Cl(-) to the water decreased with increasing
      cortisol dose, an important adaptation to dilute media. Unidirectional Na(+) and
      Cl(-) flux measurements and the application of the Ussing flux-ratio criterion
      revealed cortisol-induced active uptake of both Na(+) and Cl(-) under symmetrical
      culture conditions together with an increase in transepithelial potential
      (positive on the basolateral side). Under asymmetrical conditions, cortisol did
      not promote active ion transport across the epithelium. These experiments provide
      evidence for the direct action of cortisol on cultured pavement cell epithelia
      and, in particular, emphasize the importance of cortisol for limiting epithelial
      permeability.

PMID- 11506997
TI  - Abrogation of alpha-adrenergic vasoactivity in chronically inflamed rat knee
      joints.
AB  - It has previously been shown that chronic inflammation causes a reduction in
      sympathetic nerve-mediated vasoconstriction in rat knees. To determine whether
      this phenomenon is due to an alteration in smooth muscle adrenoceptor function,
      the present study compared the alpha-adrenoceptor profile of blood vessels
      supplying the anteromedial capsule of normal and chronically inflamed rat knee
      joints. While the rats were under urethan anesthesia, the alpha(1)-adrenoceptor
      agonists methoxamine and phenylephrine and the alpha(2)-adrenoceptor agonist
      clonidine (0.1-ml bolus; dose range 10(-12)-10(-7) mol) were applied to exposed
      normal rat knees, resulting in a dose-dependent fall in capsular perfusion.
      Comparison of drug potencies indicated that alpha(2)-adrenergic effects >
      alpha(1)-vasoactivity. One week after intra-articular injection of Freund's
      complete adjuvant to induce chronic joint inflammation, the vasoconstrictor
      effects of methoxamine, phenylephrine, and clonidine were all significantly
      attenuated compared with normal controls. These findings show that the
      preponderance of sympathetic adrenergic vasoconstriction in the anteromedial
      capsule of the rat is carried out by postjunctional alpha(2)-adrenoceptors.
      Chronic joint inflammation compromises alpha(1)- and alpha(2)-adrenoceptor
      function, and this change in alpha-adrenergic responsiveness may help explain the
      perfusion changes commonly associated with inflammatory arthritis.

PMID- 11506998
TI  - Interleukin-18 promotes sleep in rabbits and rats.
AB  - Interleukin (IL)-1beta is involved in physiological sleep regulation. IL-18 is a
      member of the IL-1 family, and its signal-transduction mechanism is similar to
      that of IL-1. Therefore, we hypothesized that IL-18 might also be involved in
      sleep regulation. Three doses of IL-18 (10, 100, and 500 ng) were injected
      intracerebroventricularly (icv) into rabbits at the onset of the dark period. The
      two higher doses of IL-18 markedly increased non-rapid eye movement sleep
      (NREMS), accompanied by increases in brain temperature (Tbr). These effects were
      lost after the heat inactivation of IL-18. The 500 ng of IL-18 injection during
      the light period also increased NREMS and Tbr. Similar results were obtained
      after icv injection of 100 ng of IL-18 into rats. Furthermore, intraperitoneal
      injection of 30 microg/kg of IL-18 slightly, but significantly, increased NREMS,
      whereas it significantly decreased electroencephalogram slow-wave activity in
      rats. Intraperitoneal IL-18 failed to induce fever. An anti-human IL-18 antibody
      had little effect on spontaneous sleep in rabbits, although the anti-IL-18
      antibody significantly attenuated muramyl dipeptide-induced sleep. These data
      suggest that IL-18 is involved in mechanisms of sleep responses to infection.

PMID- 11506999
TI  - Conditions that affect sleep alter the expression of molecules associated with
      synaptic plasticity.
AB  - Many theories propose that sleep serves a purpose in synaptic plasticity. We
      tested the hypothesis, therefore, that manipulation of sleep would affect the
      expression of molecules known to be involved in synaptic plasticity. mRNA
      expression of four molecules [brain-derived neurotrophic factor (BDNF), activity
      regulated cytoskeleton-associated protein (Arc), matrix metalloproteinase-9 (MMP
      9), and tissue plasminogen activator (tPA)] was determined after 8 h of sleep
      deprivation and after 6 h of a mild increase in ambient temperature, a condition
      that enhances sleep in rats. After sleep deprivation, BDNF, Arc, and tPA mRNAs in
      the cerebral cortex increased while MMP-9 mRNA levels decreased. Conversely,
      after enhanced ambient temperature, BDNF, Arc, and tPA mRNAs decreased while MMP
      9 mRNA increased. In the hippocampus, sleep deprivation did not significantly
      affect BDNF and tPA expression, although Arc mRNA increased and MMP-9 mRNA
      decreased. Brain temperature enhancement decreased Arc mRNA levels in the
      hippocampus but did not affect BDNF, MMP-9, or tPA in this area. Results are
      consistent with the notion that sleep plays a role in synaptic plasticity.

PMID- 11507000
TI  - Restraint increases prolactin and REM sleep in C57BL/6J mice but not in BALB/cJ
      mice.
AB  - Sleep is generally considered to be a recovery from prior wakefulness. The
      architecture of sleep not only depends on the duration of wakefulness but also on
      its quality in terms of specific experiences. In the present experiment, we
      studied the effects of restraint stress on sleep architecture and sleep
      electroencephalography (EEG) in different strains of mice (C57BL/6J and BALB/cJ).
      One objective was to determine if the rapid eye movement (REM) sleep-promoting
      effects of restraint stress previously reported for rats would also occur in
      mice. In addition, we examined whether the effects of restraint stress on sleep
      are different from effects of social defeat stress, which was found to have a non
      REM (NREM) sleep-promoting effect. We further measured corticosterone and
      prolactin levels as possible mediators of restraint stress-induced changes in
      sleep. Adult male C57BL/6J and BALB/cJ mice were subjected to 1 h of restraint
      stress in the middle of the light phase. To control for possible effects of sleep
      loss per se, the animals were also kept awake for 1 h by gentle handling.
      Restraint stress resulted in a mild increase in NREM sleep compared with
      baseline, but, overall, this effect was not significantly different from sleep
      deprivation by gentle handling. In contrast, restraint stress caused a
      significant increase in REM sleep compared with handling in the C57BL/6J mice but
      not in BALB/cJ mice. Corticosterone levels were significantly and similarly
      elevated after restraint in both strains, but prolactin was increased only in the
      C57BL/6J mice. In conclusion, this study shows that the restraint stress-induced
      increase in REM sleep in mice is strongly strain dependent. The concomitant
      increases in prolactin and REM sleep in the C57BL/6J mice, but not in BALB/cJ
      mice, suggest prolactin may be involved in the mechanism underlying restraint
      stress-induced REM sleep. Furthermore, this study confirms that different
      stressors differentially affect NREM and REM sleep. Whereas restraint stress
      promotes REM sleep in C57BL/6J mice, we previously found that in the same strain,
      social defeat stress promotes NREM sleep. As such, studying the consequences of
      specific stressful stimuli may be an important tool to unravel both the mechanism
      and function of different sleep stages.

PMID- 11507001
TI  - Parathyroid hormone-related protein: a calcium regulatory factor in sea bream
      (Sparus aurata L.) larvae.
AB  - The effects of an N-terminal peptide (amino acids 1-38) of Fugu parathyroid
      hormone-related protein (PTHrP 1-38) on calcium regulation of larval sea bream
      were investigated in seawater (36 per thousand) and after transfer to dilute
      seawater (12 per thousand). Exposure to PTHrP 1-38 evoked a 1.5-fold increase in
      calcium influx in both full-strength and dilute seawater. Calcium influx in
      dilute seawater-adapted larvae was roughly one-half that observed in full
      strength seawater controls. PTHrP 1-38 also reduced drinking of fish in seawater
      but, at all concentrations tested, was without effect in dilute seawater. The
      amount of water imbibed was 55% lower in dilute seawater than in seawater. PTHrP
      1-38 exposure affected the calcium influx route: the main contribution of calcium
      uptake shifted from intestinal absorption to extraintestinal uptake, probably by
      the induction of a dose-dependent increase in branchial (active) transport.
      Moreover, seawater-adapted fish exposed to 1 nM and 10 mM PTHrP 1-38 experienced
      a 2.5-fold reduction in overall calcium efflux. Overall, the calciotropic action
      of PTHrP 1-38 resulted in a dose-dependent increase in net calcium balance.

PMID- 11507002
TI  - Age-dependent activation of PKC isoforms by angiotensin II in the proximal
      nephron.
AB  - ANG II increases fluid absorption in proximal tubules from young rats more than
      those from adult rats. ANG II increases fluid absorption in the proximal nephron,
      in part, via activation of protein kinase C (PKC). However, it is unclear how age
      related changes in ANG II-induced stimulation of the PKC cascade differ as an
      animal matures. We hypothesized that the response of the proximal nephron to ANG
      II decreases as rats mature due to a reduction in the amount and activation of
      PKC rather than a decrease in the number or affinity of ANG II receptors. Because
      PKC translocates from the cytosol to the membrane when activated, we first
      measured PKC activity in the soluble and particulate fractions of proximal tubule
      homogenates exposed to vehicle or 10(-10) M ANG II from young (26 +/- 1 days old)
      and adult rats (54 +/- 1 days old). ANG II increased PKC activity to the same
      extent in homogenates from young rats (from 0.119 +/- 0.017 to 0.146 +/- 0.015
      U/mg protein) (P < 0.01) and adult rats (from 0.123 +/- 0.020 to 0.156 +/- 0.023
      U/mg protein) (P < 0.01). Total PKC activity did not differ between groups (0.166
      +/- 0.018 vs. 0.181 +/- 0.023). We next investigated whether activation of the
      alpha-, beta-, and gamma-PKC isoforms differed by Western blot. In homogenates
      from young rats, ANG II significantly increased activated PKC-alpha from 40.2 +/-
      6.5 to 60.2 +/- 9.5 arbitrary units (AU) (P < 0.01) but had no effect in adult
      rats (46.1 +/- 5.1 vs. 48.5 +/- 8.2 AU). Similarly, ANG II increased activated
      PKC-gamma in proximal tubules from young rats from 47.9 +/- 13.2 to 65.6 +/- 16.7
      AU (P < 0.01) but caused no change in adult rats. Activated PKC-beta, however,
      increased significantly in homogenates from both age groups. Specifically,
      activated PKC-beta increased from 8.6 +/- 1.4 to 12.2 +/- 2.1 AU (P < 0.01) in
      homogenates from nine young rats and from 19.0 +/- 5.5 to 25.1 +/- 7.1 AU (P <
      0.01) in homogenates from 12 adult rats. ANG II did not alter the amount of
      soluble PKC-alpha, -beta, and -gamma significantly. The total amount of PKC-alpha
      and -gamma did not differ between homogenates from young and adult rats, whereas
      the total amount of PKC-beta was 59.7 +/- 10.7 and 144.9 +/- 41.8 AU taken from
      young and adult rats, respectively (P < 0.05). Maximum specific binding and
      affinity of ANG II receptors were not significantly different between young and
      adult rats. We concluded that the primary PKC isoform activated by ANG II changes
      during maturation.

PMID- 11507003
TI  - Neuronal application of capsaicin modulates somatic pressor reflexes.
AB  - Static contraction of skeletal muscle elicits a reflex increase in cardiovascular
      function. Likewise, noxious stimuli activate somatic nociceptors eliciting a
      reflex increase in cardiovascular function. On the basis of recent work involving
      spinothalamic cells in the dorsal horn, we hypothesized that the dorsal horn
      cells involved in the aforementioned reflexes would be sensitized by applying
      capsaicin (Cap) to a peripheral nerve. If correct, then Cap would enhance the
      cardiovascular increases that occur when these reflexes are evoked. Cats were
      anesthetized, and the popliteal fossa was exposed. Static contraction was induced
      by electrical stimulation of the tibial nerve at an intensity that did not
      directly activate small-diameter muscle afferent fibers, whereas nociceptors were
      stimulated by high-intensity stimulation (after muscle paralysis) of either the
      saphenous nerve (cutaneous nociceptors) or a muscular branch of the tibial nerve
      (muscle nociceptors). The reflex cardiovascular responses to these perturbations
      (contraction or nociceptor stimulation) were determined before and after direct
      application of Cap (3%) onto the common peroneal nerve, using a separate group of
      cats for each reflex. Compared with control, application of Cap attenuated the
      peak change in mean arterial pressure (MAP) evoked by static contraction
      (DeltaMAP in mmHg: 38 +/- 10 before and 24 +/- 8 after ipsilateral Cap; 47 +/- 10
      before and 33 +/- 10 after contralateral Cap). On the other hand, Cap increased
      the peak change in MAP evoked by stimulation of the saphenous nerve from 57 +/- 8
      to 77 +/- 9 mmHg, as well as the peak change in MAP elicited by activation of
      muscle nociceptors (36 +/- 9 vs. 56 +/- 14 mmHg). These results show that the
      reflex cardiovascular increases evoked by static muscle contraction and noxious
      input are differentially affected by Cap application to the common peroneal
      nerve. We hypothesize that a Cap-induced alteration in dorsal horn processing is
      the locus for this divergent effect on these reflexes.

PMID- 11507004
TI  - Mineralocorticoids upregulate arterial contraction to epidermal growth factor.
AB  - The present studies test the hypothesis that contraction to EGF is dependent on
      mineralocorticoids and/or an elevation in systolic blood pressure (SBP).
      Endothelium-denuded thoracic aortas from sham normotensive, N(omega)-nitro-L
      arginine (L-NNA) hypertensive, Wistar-Kyoto (WKY), and spontaneously hypertensive
      rats (SHR) were used in isolated tissue-bath experiments. Maximal contraction to
      epidermal growth factor [EGF; percentage of phenylephrine (PE; 10 umol/l)-induced
      contraction] was greater in strips from L-NNA (32 +/- 5%) and SHR (53 +/- 8%)
      rats compared with sham and WKY rats (17 +/- 1 and 12 +/- 4%, respectively).
      Wistar-Furth rats became only mildly hypertensive when given DOCA salt (134 +/- 6
      mmHg) compared with Wistar rats (176 +/- 9 mmHg), but aortas from both strains
      had a similarly enhanced contraction to EGF (approximately 9 times the maximal
      contraction of sham aorta). Furthermore, in vitro incubation of aortas from
      Wistar and Wistar-Furth rats with aldosterone (10 nmol/l) increased EGF-receptor
      mRNA expression by >50%. These data indicate that arterial contraction to EGF may
      occur independent of hypertension and be stimulated by mineralocorticoids.

PMID- 11507005
TI  - Cardiovascular effects of vasopressin following V(1) receptor blockade compared
      to effects of nitroglycerin.
AB  - Studies to more clearly determine the mechanisms associated with arginine
      vasopressin (AVP)-induced vasodilation were performed in normal subjects and in
      quadriplegic subjects with impaired efferent sympathetic responses. Studies to
      compare the effects of AVP with the hemodynamic effects of nitroglycerin, an
      agent that primarily affects venous capacitance vessels, were also performed in
      normal subjects. Incremental infusions of AVP following V(1)-receptor blockade
      resulted in equivalent reductions in systemic vascular resistance (SVRI) in
      normal and in quadriplegic subjects. However, there were major differences in the
      effect on mean arterial pressure (MAP), which was reduced in quadriplegic
      subjects but did not change in normal subjects. This difference in MAP can be
      attributed to a difference in the magnitude of increase in cardiac output (CI),
      which was twofold greater in normal than in quadriplegic subjects. These
      observations are consistent with AVP-induced vasodilation of arterial resistance
      vessels with reflex sympathetic enhancement of CI and are clearly different from
      the hemodynamic effects of nitroglycerin, i.e., reductions in MAP, CI, and
      indexes of cardiac preload, with only minor changes in SVRI.

PMID- 11507006
TI  - The influence of topical capsaicin on the local thermal control of skin blood
      flow in humans.
AB  - To test whether heat-sensitive receptors participate in the cutaneous vascular
      responses to direct heating, we monitored skin blood flow (SkBF; laser Doppler
      flowmetry) where the sensation of heat was induced either by local warming
      (T(Loc); Peltier cooling/heating unit) or by both direct warming and chemical
      stimulation of heat-sensitive nociceptors (capsaicin). In part I, topical
      capsaicin (0.075 or 0.025%) was applied to 12 cm(2) of skin 1 h before stepwise
      local warming of untreated and capsaicin-treated forearm skin. Pretreatment with
      0.075% capsaicin cream shifted the SkBF/T(Loc) relationship to lower temperatures
      by an average of 6 +/- 0.8 degrees C (P < 0.05). In part II, we used a
      combination of topical capsaicin (0.025%) and local warming to evoke thermal
      sensation at one site and only local warming to evoke thermal sensation at a
      separate site. Cutaneous vasomotor responses were compared when the temperatures
      at these two sites were perceived to be the same. SkBF differed significantly
      between capsaicin and control sites when compared on the basis of actual
      temperatures, but that difference became insignificant when compared on the basis
      of the perceived temperatures. These data suggest heat-sensitive nociceptors are
      important in the cutaneous vasodilator response to local skin warming.

PMID- 11507007
TI  - Gastrin-releasing peptides from Xenopus laevis: purification, characterization,
      and myotropic activity.
AB  - Two molecular forms of gastrin-releasing peptide (GRP) were isolated from an
      extract of the intestine of the tetraploid frog Xenopus laevis. The primary
      structure of GRP-1 (APTSQQHTEQ(10)LSRSNINTRG(20) SHWAVGHLM.NH(2)) differs from
      that of GRP-2 by a single amino acid substitution (Asn(15)--> Thr(15)). GRP-(20
      29) peptide (neuromedin C) was also isolated from the extract. Synthetic GRP-1
      produced concentration-dependent contractions of longitudinal smooth muscle
      strips from Xenopus cardiac stomach (pD(2) = 8.93 +/- 0.32; n = 6). The responses
      were unaffected by tetrodotoxin, atropine, and methysergide, indicating a direct
      action of the peptide on smooth muscle cells. GRP-1 elicited concentration
      dependent relaxations of precontracted (5 microM carbachol) circular smooth
      muscle strips from the same region (pD(2) = 8.96 +/- 0.21; n = 8). The responses
      were significantly (P < 0.05) attenuated (71 +/- 24% decrease in maximum
      response; n = 6) by indomethacin, indicating mediation, at least in part, by
      prostanoids. Despite the fact that Xenopus GRP-1 differs from pig GRP at 15 amino
      acid sites, both peptides are equipotent and equally effective for both
      contractile and relaxant responses, demonstrating that selective evolutionary
      pressure has acted to conserve the functional COOH-terminal domain in the
      peptide. The data suggest a physiologically important role for GRP in the
      regulation of gastric motility in X. laevis.

PMID- 11507008
TI  - Spinal and cranial contributions to total cerebrospinal fluid transport.
AB  - In this study, we quantified cerebrospinal fluid (CSF) transport from the cranial
      and spinal subarachnoid spaces separately in sheep and determined the relative
      proportion of total CSF drainage that occurred from both CSF compartments.
      Cranial and spinal CSF systems were separated by placement of an extradural
      ligature over the spinal cord between C(1) and C(2). In one approach, two
      different radiolabeled human serum albumins (HSA) were introduced into the
      appropriate CSF compartment by a perfusion system (method 1) or as a bolus
      injection (method 2). Plasma tracer recoveries in conjunction with a mass balance
      equation were used to estimate CSF transport. In method 3, catheters connected to
      reservoirs filled with artificial CSF were introduced into the cranial and spinal
      CSF compartments. Incremental CSF pressures were established in each CSF system,
      and the corresponding steady-state flow rates were measured. Total CSF drainage
      ranged from 0.51 to 0.75 ml. h(-1). cmH(2)O(-1). Expressed as a percentage of the
      total CSF transport, the ratios of cranial-to-spinal clearance estimated from
      methods 1, 2, and 3 were 75:25, 88:12, and 75:25, respectively. Primarily on the
      basis of the data derived from methods 1 and 3, we conclude that the spinal
      subarachnoid compartment has an important role in CSF clearance and is
      responsible for approximately one-fourth of total CSF transport.

PMID- 11507009
TI  - The alpha(1)- and alpha(2)-isoforms of Na-K-ATPase play different roles in
      skeletal muscle contractility.
AB  - The Na-K-ATPase, which maintains the Na(+) and K(+) gradients across the plasma
      membrane, can play a major role in modulation of skeletal muscle contractility.
      Although both alpha(1)- and alpha(2)-isoforms of the Na-K-ATPase are expressed in
      skeletal muscle, the physiological significance of these isoforms in
      contractility is not known. Evaluation of the contractile parameters of mouse
      extensor digitorum longus (EDL) was carried out using gene-targeted mice lacking
      one copy of either the alpha(1)- or alpha(2)-isoform gene of the Na-K-ATPase. The
      EDL muscles from heterozygous mice contain approximately one-half of the alpha(1)
      or alpha(2)-isoform, respectively, which permits differentiation of the
      functional roles of these isoforms. EDL from the alpha(1)(+/-) mouse shows lower
      force compared with wild type, whereas that from the alpha(2)(+/-) mouse shows
      greater force. The different functional roles of these two isoforms are further
      demonstrated because inhibition of the alpha(2)-isoform with ouabain increases
      contractility of alpha(1)(+/-) EDL. These results demonstrate that the Na-K
      ATPase alpha(1)- and alpha(2)-isoforms may play different roles in skeletal
      muscle contraction.

PMID- 11507010
TI  - Chronic hypoxia alters prejunctional alpha(2)-receptor function in vascular
      adrenergic nerves of adult and fetal sheep.
AB  - The impact of development and chronic high-altitude hypoxia on the function of
      prejunctional alpha(2)-adrenoceptors was studied by measuring norepinephrine
      release in vitro from fetal and adult sheep middle cerebral and facial arteries.
      Blockade of prejunctional alpha(2)-adrenoceptors with idazoxan significantly
      increased stimulation-evoked norepinephrine release in normoxic arteries. This
      effect was eliminated after chronic hypoxia in cerebral arteries, with a tendency
      to decline in fetal facial arteries. After chronic hypoxia, the capacity to
      release norepinephrine declined in fetal middle cerebral arteries with a similar
      trend in facial arteries. Norepinephrine release was maintained in adult
      arteries. During development, stimulation-evoked norepinephrine release from
      middle cerebral and facial arteries was higher compared with adult arteries. In
      fetal arteries, adrenergic nerve function declined after chronic hypoxia.
      However, in adult arteries, adrenergic nerves adapted to chronic hypoxia by
      maintaining overall function. This differential adaptation of adrenergic nerves
      in fetal arteries may reflect differences in fetal distribution of blood flow in
      response to chronic hypoxic stress.

PMID- 11507011
TI  - Differential roles for glutamate receptor subtypes within commissural NTS in
      cardiac-sympathetic reflex.
AB  - Ischemic stimulation of cardiac receptors evokes excitatory sympathetic reflexes.
      Although the nucleus of the solitary tract (NTS) is an important site for
      integration of visceral afferents, its involvement in the cardiac-renal
      sympathetic reflex remains to be fully defined. This study examined the role of
      glutamate receptor subtypes in the commissural NTS in the sympathetic responses
      to stimulation of cardiac receptors. Renal sympathetic nerve activity (RSNA) was
      recorded in anesthetized rats. Cardiac receptors were stimulated by epicardial
      application of bradykinin (BK; 10 microg/ml). Application of BK significantly
      increased the mean arterial pressure from 78.2 +/- 2.2 to 97.5 +/- 2.9 mmHg and
      augmented RSNA by 38.5 +/- 2.5% (P < 0.05). Bilateral microinjection of 10 pmol
      of 6-cyano-7-nitroquinoxaline-2,3-dione, a non-N-methyl-D-aspartate (NMDA)
      antagonist, into the commissural NTS eliminated the pressor and RSNA responses to
      BK application in 10 rats. However, microinjection of 2-amino-5
      phosphonopentanoic acid (0.1 and 1 nmol, n = 8), an NMDA- receptor antagonist, or
      alpha-methyl-4-carboxyphenylglycine (0.1 and 1 nmol, n = 5), a glutamate
      metabotropic receptor antagonist, failed to attenuate significantly the pressor
      and RSNA responses to stimulation of cardiac receptors with BK. Thus this study
      suggests that non-NMDA, but not NMDA and glutamate metabotropic, receptors in the
      commissural NTS play an important role in the sympathoexcitatory reflex response
      to activation of cardiac receptors during myocardial ischemia.

PMID- 11507012
TI  - Spironolactone reduces cerebral infarct size and EGF-receptor mRNA in stroke
      prone rats.
AB  - Remodeling of the cerebral vasculature contributes to the pathogenesis of
      cerebral ischemia. Remodeling is caused by increased smooth muscle proliferation
      and may be due to an increase in the responsiveness of vascular cells to
      epidermal growth factor (EGF). Aldosterone is a risk factor for stroke, and the
      literature suggests it may play a role in increasing the expression of the
      receptor for EGF (EGFR). We hypothesized that mRNA for the EGF-stimulated pathway
      would be elevated in the vasculature of stroke-prone spontaneously hypertensive
      rats (SHRSP) and that this and experimental ischemic cerebral infract size would
      be reduced by aldosterone inhibition with spironolactone. We found that
      spironolactone treatment reduced the size of cerebral infarcts after middle
      cerebral artery occlusion in SHRSP (51.69 +/- 3.60 vs. 22.00 +/- 6.69% of
      hemisphere-infarcted SHRSP vs. SHRSP + spironolactone P < 0.05). Expression of
      EGF and EGFR mRNA was higher in cerebral vessels and aorta from adult SHRSP
      compared with Wistar-Kyoto rats. Only the expression of EGFR mRNA was elevated in
      the young SHRSP. Spironolactone reduced the EGFR mRNA expression in the aorta
      (1.09 +/- 0.25 vs. 0.56 +/- 0.11 phosphorimage units SHRSP vs. SHRSP +
      spironolactone P < 0.05) but had no effect on EGF mRNA. In vitro incubation of
      aorta with aldosterone +/- spironolactone produced similar results, suggesting a
      direct effect of aldosterone. Thus spironolactone may reduce the size of cerebral
      infarcts via a reduction in the expression of the EGFR mRNA, leading to reduced
      remodeling.

PMID- 11507013
TI  - Seasonal changes in serum leptin, food intake, and body weight in photoentrained
      woodchucks.
AB  - Male woodchucks (Marmota monax) were maintained in northern vs. southern
      hemisphere photoperiods, provided feed and water ad libitum, and evaluated every
      2 wk for 23 mo for body weight, absolute and relative food intake, body
      temperature, serum testosterone, and serum concentrations of leptin measured
      using an anti-mouse leptin enzyme-linked immunoassay. During late spring and
      summer, body weight increased 56 +/- 4% above winter nadirs, and during the
      autumn and early winter weights decreased 27 to 43% below midsummer maxima. Serum
      leptin initially increased during increases in body weight, in the late spring,
      reached peak values (490 +/- 32 pg/ml) in summer during the initial decline in
      body weight, and later decreased along with body weight to reach basal values (20
      +/- 5 pg/ml) in late winter. Spontaneous declines in food intakes in summer began
      2-6 wk before resulting declines in body weight and occurred during increases in
      leptin >100 pg/ml. The rate of decline in food intakes was greatest when serum
      leptin was at or near peak values. Food intake increased in late winter when
      leptin was low and 7-10 wk before resulting increases in body weight. Testis
      recrudescence occurred when leptin was declining to near basal levels. The
      results suggest that leptin is involved in the hormonal regulation of the
      circannual cycle in the drive for voluntary food intake in this species.

PMID- 11507014
TI  - Programming effects in sheep of prenatal growth restriction and glucocorticoid
      exposure.
AB  - Our aim was to determine the postnatal effects of single and repeated
      glucocorticoid injections during late gestation. Repeated (104, 111, 118, 125
      days) or single (104 days) injections of betamethasone or saline were given to
      the ewe or by ultrasound guided injection to the fetus (term 150 days). Lambs
      were born spontaneously and studied at 3 and 6 mo and 1 yr of age. Arterial
      pressure was measured at each age, and we performed intravenous glucose tolerance
      tests at 6 mo and 1 yr. Repeated maternal, but not single maternal or fetal,
      betamethasone injections prolonged gestation, reduced weight at birth and 3 mo,
      and was associated with low arterial pressure at 3 mo but not at 6 mo and 1 yr.
      Glucose metabolism was altered in all betamethasone treatment groups, regardless
      of the number or route of injections. Our data demonstrate that glucocorticoid
      induced fetal growth restriction is associated with a transient reduction in
      postnatal arterial pressure, but glucocorticoid exposure with or without growth
      restriction alters glucose metabolism.

PMID- 11507015
TI  - Calcium deprivation alters gustatory-evoked activity in the rat nucleus of the
      solitary tract.
AB  - Calcium-deprived rats develop a compensatory appetite for substances that contain
      calcium. To investigate the role of gustatory factors in calcium appetite, we
      recorded the extracellular activity of single neurons in the nucleus of the
      solitary tract of calcium-deprived and replete rats. The activity evoked by a
      broad array of taste stimuli was examined in 51 neurons from replete rats and 47
      neurons from calcium-deprived rats. There were no differences between the groups
      in the responses of all neurons combined. However, neurons with sugar-oriented
      response profiles gave significantly larger responses to 3, 10, and 100 mM
      CaCl(2) in the calcium-deprived group than did corresponding cells in the replete
      group. This difference in taste-evoked responding may underlie an increase in the
      palatability of CaCl(2) and, in turn, contribute to the expression of calcium
      appetite.

PMID- 11507016
TI  - Alpha-2 and beta-adrenergic receptors mediate NE's biphasic effects on rat thick
      ascending limb chloride flux.
AB  - The sympathetic neurotransmitter norepinephrine (NE) influences renal sodium
      excretion via activation of adrenergic receptors. The thick ascending limb (THAL)
      possesses both alpha-2 and beta-adrenergic receptors. However, the role(s)
      different adrenergic receptors play in how isolated THALs respond to NE are
      unclear. We tested the hypothesis that both alpha-2 and beta-adrenergic receptors
      are responsive to NE in the isolated THAL, with alpha-2 receptors inhibiting and
      beta-receptors stimulating chloride flux (J(Cl)). THALs from male Sprague-Dawley
      rats were perfused in vitro, and the effects of 1) incremental NE, 2) the alpha-2
      agonist clonidine, and 3) the beta-agonist isoproterenol on J(Cl) were measured.
      Low concentrations (0.1 nM) of NE decreased J(Cl) from a rate of 114.2 +/- 8.1 to
      93.5 +/- 14.6 pmol. mm(-1). min(-1) (P < 0.05), with the nadir occurring at 1 nM
      (67.7 +/- 8.8 pmol. mm(-1). min(-1); P < 0.05). In contrast, greater
      concentrations of NE significantly increased J(Cl) from the nadir to a maximal
      rate of 131.0 +/- 28.5 pmol. mm(-1). min(-1) at 10 microM (P < 0.05). To evaluate
      the adrenergic receptors mediating these responses, the THAL J(Cl) response to NE
      was measured in the presence of selective antagonists of beta- and alpha-2
      receptors. A concentration of NE (1 microM), which alone tended to increase
      J(Cl), decreased THAL J(Cl) (from 148.9 +/- 16.4 to 76.2 +/- 13.6 pmol. mm(-1).
      min(-1); P < 0.01) in the presence of the beta-antagonist propranolol. In
      contrast, a concentration of NE (0.1 microM), which alone tended to decrease
      J(Cl), increased THAL J(Cl) (from 85.5 +/- 20.1 to 111.8 +/- 20.1 pmol. mm(-1).
      min(-1); P < 0.05) in the presence of the alpha-2 antagonist rauwolscine. To
      further clarify the role of different adrenergic receptors, selective adrenergic
      agonists were used. The alpha-2 agonist clonidine decreased J(Cl) from 102.4 +/-
      9.9 to 54.0 +/- 15.7 pmol. mm(-1). min(-1), a reduction of 49.1 +/- 11.0% (P <
      0.02). In contrast, the beta-agonist isoproterenol stimulated J(Cl) from 95.3 +/-
      11.6 to 144.1 +/- 15.0 pmol. mm(-1). min(-1), an increase of 56 +/- 14% (P <
      0.01). We conclude that 1) the sympathetic neurotransmitter NE exerts
      concentration-dependent effects on J(Cl) in the isolated rat THAL, 2) selective
      alpha-2 receptor activation inhibits THAL J(Cl), and 3) selective beta-receptor
      activation stimulates THAL J(Cl). These data indicate the response elicited by
      the isolated rat THAL to NE is dependent on the neurotransmitter concentration,
      such that application of NE in vitro biphasically modulates J(Cl) via
      differential activation of alpha-2 and beta-adrenergic receptors in a
      concentration-dependent manner.

PMID- 11507017
TI  - Role of the renin-angiotensin system during alterations of sodium intake in
      conscious mice.
AB  - The present studies were performed to quantify circulating components of the
      renin-angiotensin-aldosterone axis and to determine the functional importance of
      this system during alterations in sodium intake in conscious mice. Increasing
      sodium intake from approximately 200 to 1,000 microeq/day significantly decreased
      plasma renin concentration from 472 +/- 96 to 304 +/- 83 ng ANG I. ml(-1). h(-1)
      (n = 5) but did not alter plasma renin activity from the low-sodium level of 7.7
      +/- 1.1 ng ANG I. ml(-1). h(-1). Despite the elevated plasma renin concentration,
      plasma ANG II in mice on low-sodium level averaged 14 +/- 3 pg/ml and was
      significantly suppressed to 6 +/- 1 pg/ml by high-sodium intake (n = 7).
      Consistent with the modulation of ANG II, plasma aldosterone significantly
      decreased from 41 +/- 8 to 8 +/- 3 ng/dl when sodium intake was elevated (n = 6).
      In a final set of experiments, the continuous infusion of ANG II (20 ng. kg(-1).
      min(-1)) led to a mild salt-sensitive increase in mean arterial pressure from 108
      +/- 2 to 131 +/- 2 mmHg as sodium intake was varied from low to high (n = 7). In
      vehicle-infused mice, mean arterial pressure was unaltered from 109 +/- 2 mmHg
      when sodium intake was increased (n = 6). These studies indicate that the
      physiological suppression of circulating ANG II may be required to maintain a
      constancy of arterial pressure during alterations in sodium intake in normal
      mice.

PMID- 11507018
TI  - Corticosterone and insulin interact to regulate glucose and triglyceride levels
      during stress in a bird.
AB  - Captive European starlings (Sturnus vulgaris) were exposed to the stress of
      handling and restraint while corticosterone, glucose, and triglyceride
      concentrations were monitored in blood plasma. In saline-injected controls, basal
      samples were taken within 3 min of disturbance with subsequent samples taken at
      40, 70, and 150 min. This was repeated at two times during the daily cycle (day
      and night) on two different photoperiods: short and long days. During both
      photoperiods, corticosterone concentrations approximately tripled (compared with
      a sixfold increase in free-living starlings) and triglyceride concentrations
      decreased 25-45% in response to stress at both times of the day, whereas an
      approximately 25% stress-induced hyperglycemia occurred only at night. Exogenous
      corticosterone (200 microg), 1.0 or 4.0 IU/kg of insulin, or a combination of
      corticosterone with each insulin dose was then separately administered to alter
      the above responses. Insulin did not affect corticosterone or triglyceride
      concentrations but resulted in a dose-dependent hypoglycemia of 10-40%. Injected
      corticosterone resulted in supraphysiological corticosterone concentrations
      (three- to fivefold higher than normal), yet it did not affect the already
      altered plasma glucose or triglyceride concentrations. This suggests that glucose
      output and triglyceride decreases were already maximal in response to handling
      and restraint. However, the low glucose concentrations resulting from exogenous
      insulin returned to basal quicker with exogenous corticosterone but only during
      the day. No response to either hormone showed photoperiodic differences. These
      data suggest that corticosterone's role in metabolism changes to meet varying
      energetic demands throughout the day.

PMID- 11507019
TI  - Interleukin-15 and interleukin-2 enhance non-REM sleep in rabbits.
AB  - Interleukin (IL)-15 and -2 share receptor- and signal-transduction pathway (Jak
      STAT pathway) components. IL-2 is somnogenic in rats but has not been tested in
      other species. Furthermore, the effects of IL-15 on sleep have not heretofore
      been described. We investigated the somnogenic actions of IL-15 in rabbits and
      compared them with those of IL-2. Three doses of IL-15 or -2 (10, 100, and 500
      ng) were injected intracerebroventriculary at the onset of the dark period. In
      addition, 500 ng of IL-15 and -2 were injected 3 h after the beginning of the
      light period. IL-15 dose dependently increased non-rapid eye movement sleep
      (NREMS) and induced fever. IL-15 inhibited rapid eye movement sleep (REMS) after
      its administration during the light period; however, all doses of IL-15 failed to
      affect REMS if given at dark onset. IL-2 also dose dependently increased NREMS
      and fever. IL-2 inhibited REMS, and this effect was observed only in the light
      period. IL-15 and -2 enhanced electroencephalographic (EEG) slow waves during the
      initial 9-h postinjection period, then, during hours 10-23 postinjection, reduced
      EEG slow-wave activity. Current data support the notion that the brain cytokine
      network is involved in the regulation of sleep.

PMID- 11507020
TI  - Intestinal permeability is reduced and IL-10 levels are increased in septic IL-6
      knockout mice.
AB  - Sepsis is associated with increased intestinal permeability, but mediators and
      mechanisms are not fully understood. We examined the role of interleukin (IL)-6
      and IL-10 in sepsis-induced increase in intestinal permeability. Intestinal
      permeability was measured in IL-6 knockout (IL-6 -/-) and wild-type (IL-6 +/+)
      mice 16 h after induction of sepsis by cecal ligation and puncture or sham
      operation. In other experiments, mice or intestinal segments incubated in Ussing
      chambers were treated with IL-6 or IL-10. Intestinal permeability was assessed by
      determining the transmucosal transport of the 4.4-kDa marker fluorescein
      isothiocyanate conjugated dextran and the 40-kDa horseradish peroxidase.
      Intestinal permeability for both markers was increased in septic IL-6 +/+ mice
      but not in septic IL-6 -/- mice. Treatment of nonseptic mice or of intestinal
      segments in Ussing chambers with IL-6 did not influence intestinal permeability.
      Plasma IL-10 levels were increased in septic IL-6 -/- mice, and treatment of
      septic mice with IL-10 resulted in reduced intestinal permeability. Increased
      intestinal permeability during sepsis may be regulated by an interaction between
      IL-6 and IL-10. Treatment with IL-10 may prevent the increase in mucosal
      permeability during sepsis.

PMID- 11507034
TI  - p14(ARF) modulates the cytolytic effect of ONYX-015 in mesothelioma cells with
      wild-type p53.
AB  - ONYX-015 has been reported to kill selectively tumor cells lacking functional
      p53. Genetic alterations of INK4a/ARF locus, which is a predominant event in
      malignant pleural mesothelioma, may result in loss of p14(ARF) and subsequent
      disruption of p53 pathway in cancer cells. In the present study, ONYX-015 was
      able to kill three mesothelioma cell lines (H28, H513, and 211H) with wild-type
      p53 but lacking p14(ARF). In contrast, MS-1 mesothelioma cells, which expressed
      both p53 and p14(ARF), were resistant to ONYX-015. Introducing p14(ARF) gene into
      the H28 cell, a mesothelioma cell without p14(ARF) expression, significantly
      increased the resistance of this cell line to the cytolytic effect of ONYX-015.
      Our results suggest that human mesotheliomas with wild-type p53 yet lacking
      p14(ARF) are potential candidates for ONYX-015 therapy.

PMID- 11507035
TI  - Spontaneous cytotoxic T-cell responses against survivin-derived MHC class I
      restricted T-cell epitopes in situ as well as ex vivo in cancer patients.
AB  - Recent advances in therapeutic tumor vaccinations necessitate the identification
      of broadly expressed, immunogenic tumor antigens that are not prone to immune
      selection. To this end, the human inhibitor of apoptosis, survivin, is a prime
      candidate because it is expressed in most human neoplasms but not in normal,
      differentiated tissues. Here, we demonstrate spontaneous cytotoxic T-cell
      responses against survivin-derived MHC class I-restricted T-cell epitopes in
      breast cancer, leukemia, and melanoma patients both in situ as well as ex vivo.
      Moreover, survivin-reactive T cells isolated by magnetic beads coated with
      MHC/peptide complexes were cytotoxic against HLA-matched tumors of different
      tissue types. Being a universal tumor antigen, survivin may serve as a widely
      applicable target for anticancer immunotherapy.

PMID- 11507036
TI  - A novel human cell culture model for the study of familial prostate cancer.
AB  - Research into molecular and genetic mechanisms underlying familial prostate
      cancer would be greatly advanced by in vitro models of prostate tumor cells
      representing primary tumors. We have successfully established an immortalized
      human prostate epithelial cell culture derived from primary tumors of familial
      prostate cancer patients with telomerase. The actively proliferating early
      passaged 957E cells were transduced through infection with a retrovirus
      expressing the human telomerase catalytic subunit, human telomerase reverse
      transcriptase (hTERT). A high level of telomerase activity was detected in
      957E/hTERT cells, but not in 957E cells. 957E/hTERT cells are currently growing
      well at passage 40, whereas 957E cells senesced at passage 5. 957E/hTERT cells
      exhibit epithelial morphology. Expression of an androgen-regulated prostate
      specific homeobox gene NKX3.1 and an epithelial cell-specific cytokeratin 8, but
      not prostate specific antigen or androgen receptor, was detected in 957E/hTERT
      cells. Prostatic stem cell antigen and p16 were also expressed in this line.
      957E/hTERT cells showed growth inhibition when exposed to retinoic acid and
      transforming growth factor beta1, potent inhibitors of prostate epithelial cell
      growth. Chromosome analysis showed that the 957E/hTERT cell line (passage 10) was
      near diploid human male (XY), with most chromosome counts in the 44-46 range.
      However, there was random loss of chromosomes 8, 13, X, Y, and alteration in
      chromosome 4q. The late passage 957E/hTERT cell line (passage 32) was
      karyologically similar to the early passage 957E/hTERT cell line (passage 10) and
      also had the same alteration of 4q observed in the early passage 957E/hTERT cell
      line (passage 10) as well as a trisomy of chromosome 20. The well-characterized
      human cancer lines derived from such patients will be useful for the
      identification and characterization of prostate cancer susceptibility genes. This
      is the first documented case of an established human prostate cancer cell line
      from primary tumor of a familial prostate cancer patient.

PMID- 11507037
TI  - Analysis of gene expression identifies candidate markers and pharmacological
      targets in prostate cancer.
AB  - Detection, treatment, and prediction of outcome for men with prostate cancer
      increasingly depend on a molecular understanding of tumor development and
      behavior. We characterized primary prostate cancer by monitoring expression
      levels of more than 8900 genes in normal and malignant tissues. Patterns of gene
      expression across tissues revealed a precise distinction between normal and tumor
      samples, and revealed a striking group of about 400 genes that were overexpressed
      in tumor tissues. We ranked these genes according to their differential
      expression in normal and cancer tissues by selecting for highly and specifically
      overexpressed genes in the majority of cancers with correspondingly low or absent
      expression in normal tissues. Several such genes were identified that act within
      a variety of biochemical pathways and encode secreted molecules with diagnostic
      potential, such as the secreted macrophage inhibitory cytokine, MIC-1. Other
      genes, such as fatty acid synthase, encode enzymes known as drug targets in other
      contexts, which suggests new therapeutic approaches.

PMID- 11507038
TI  - Estrogen receptor status in breast cancer is associated with remarkably distinct
      gene expression patterns.
AB  - To investigate the phenotype associated with estrogen receptor alpha (ER)
      expression in breast carcinoma, gene expression profiles of 58 node-negative
      breast carcinomas discordant for ER status were determined using DNA microarray
      technology. Using artificial neural networks as well as standard hierarchical
      clustering techniques, the tumors could be classified according to ER status, and
      a list of genes which discriminate tumors according to ER status was generated.
      The artificial neural networks could accurately predict ER status even when
      excluding top discriminator genes, including ER itself. By reference to the
      serial analysis of gene expression database, we found that only a small
      proportion of the 100 most important ER discriminator genes were also regulated
      by estradiol in MCF-7 cells. The results provide evidence that ER+ and ER- tumors
      display remarkably different gene-expression phenotypes not solely explained by
      differences in estrogen responsiveness.

PMID- 11507039
TI  - Phosphatidylinositol-3-OH Kinase (PI3K)/AKT2, activated in breast cancer,
      regulates and is induced by estrogen receptor alpha (ERalpha) via interaction
      between ERalpha and PI3K.
AB  - We have shown previously that the AKT2 pathway is essential for cell survival and
      important in malignant transformation. In this study, we demonstrate elevated
      kinase levels of AKT2 and phosphatidylinositol-3-OH kinase (PI3K) in 32 of 80
      primary breast carcinomas. The majority of the cases with the activation are
      estrogen receptor alpha (ERalpha) positive, which prompted us to examine whether
      AKT2 regulates ERalpha activity. We found that constitutively activated AKT2 or
      AKT2 activated by epidermal growth factor or insulin-like growth factor-1
      promotes the transcriptional activity of ERalpha. This effect occurred in the
      absence or presence of estrogen. Activated AKT2 phosphorylates ERalpha in vitro
      and in vivo, but it does not phosphorylate a mutant ERalpha in which ser-167 was
      replaced by Ala. The PI3K inhibitor, wortmannin, abolishes both the
      phosphorylation and transcriptional activity of ERalpha induced by AKT2. However,
      AKT2-induced ERalpha activity was not inhibited by tamoxifen but was completely
      abolished by ICI 164,384, implicating that AKT2-activated ERalpha contributes to
      tamoxifen resistance. Moreover, we found that ERalpha binds to the p85alpha
      regulatory subunit of PI3K in the absence or presence of estradiol in epithelial
      cells and subsequently activates PI3K/AKT2, suggesting ERalpha regulation of
      PI3K/AKT2 through a nontranscriptional and ligand-independent mechanism. These
      data indicate that regulation between the ERalpha and PI3K/AKT2 pathway (ERalpha
      PI3K/AKT2-ERalpha) may play an important role in pathogenesis of human breast
      cancer and could contribute to ligand-independent breast cancer cell growth.

PMID- 11507040
TI  - The EWS protein is dispensable for Ewing tumor growth.
AB  - EWS encodes a ubiquitously expressed RNA binding protein with largely unknown
      function. In Ewing sarcoma family tumors (EFT), one allele is rearranged with an
      ETS gene. This is the first description of an EFT with a complete EWS deficiency
      in the presence of two copies of a rearranged chromosome 22 carrying an
      interstitial EWS-FLI1 translocation. Absence of EWS protein suggested that it is
      dispensable for EFT growth. By sequencing of EWS cDNA from unrelated EFTs, we
      excluded inactivation of EWS as a general mechanism in EFT pathogenesis. Rather,
      EWS was found to be uniformly expressed in two splicing variants of similar
      abundancy, EWSalpha and EWSbeta, which differ in a single amino acid. Three EWS
      negative cell lines were established, which will serve as valuable models to
      study normal and aberrant EWS function upon reintroduction into the tumor cells.

PMID- 11507041
TI  - High incidence of somatic mitochondrial DNA mutations in human ovarian
      carcinomas.
AB  - To investigate the potential role of somatic mitochondrial DNA (mtDNA) mutations
      in tumorigenesis, the occurrence of mutations in mtDNA of ovarian carcinomas was
      studied. We sequenced the D-loop region of mtDNA of 15 primary ovarian carcinomas
      and their matched normal controls. Somatic mtDNA mutations were detected in 20%
      (3 of 15) tumor samples carrying single or multiple changes. Complete sequence
      analysis of the mtDNA genomes of another 10 pairs of primary ovarian carcinomas
      and control tissues revealed somatic mtDNA mutations in 60% (6 of 10) of tumor
      samples. Most of these mutations were homoplasmic, and most were T-->C or G-->A
      transitions, but one represented a differential length within a run of identical
      C residues. A region of mtDNA sequence including the 16S and 12S rRNA genes, the
      D-loop and the cytochrome b gene, may represent the zone of preferred mtDNA
      mutation in ovarian cancer. The high incidence of mtDNA mutations found in
      ovarian carcinomas and other human cancers suggests that genetic instability of
      mtDNA might play a significant role in tumorigenesis.

PMID- 11507042
TI  - Cell growth inhibition by the multifunctional multivalent zinc-finger factor
      CTCF.
AB  - The 11-zinc finger protein CCTC-binding factor (CTCF) employs different sets of
      zinc fingers to form distinct complexes with varying CTCF- target sequences
      (CTSs) that mediate the repression or activation of gene expression and the
      creation of hormone-responsive gene silencers and of diverse vertebrate enhancer
      blocking elements (chromatin insulators). To determine how these varying effects
      would integrate in vivo, we engineered a variety of expression systems to study
      effects of CTCF on cell growth. Here we show that ectopic expression of CTCF in
      many cell types inhibits cell clonogenicity by causing profound growth
      retardation without apoptosis. In asynchronous cultures, the cell-cycle profile
      of CTCF-expressing cells remained unaltered, which suggested that progression
      through the cycle was slowed at multiple points. Although conditionally induced
      CTCF caused the S-phase block, CTCF can also arrest cell division. Viable CTCF
      expressing cells could be maintained without dividing for several days. While MYC
      is the well-characterized CTCF target, the inhibitory effects of CTCF on cell
      growth could not be ascribed solely to repression of MYC, suggesting that
      additional CTS-driven genes involved in growth-regulatory circuits, such as
      p19ARF, are likely to contribute to CTCF-induced growth arrest. These findings
      indicate that CTCF may regulate cell-cycle progression at multiple steps within
      the cycle, and add to the growing evidence for the function of CTCF as a tumor
      suppressor gene.

PMID- 11507043
TI  - The transcriptional repressor of p16/Ink4a, Id1, is up-regulated in early
      melanomas.
AB  - The helix-loop-helix transcription factor Id1 coordinates cell growth and
      differentiation pathways within mammalian cells and has been implicated in
      regulating G(1)-S phase cell cycle transitions. Recently Id1 has been shown to
      repress Ets- and E-protein-mediated transactivation of p16/Ink4a. Because the
      p16/Ink4a protein has been demonstrated to be inactivated in subsets of familial
      and sporadic melanomas, we sought to determine whether Id1 regulation of
      p16/Ink4a expression might be involved in the development of this human tumor.
      Here we evaluate 21 melanocytic lesions at various stages of malignant
      progression from common melanocytic nevi to metastatic melanomas and examine
      these lesions for Id1 and p16/Ink4a expression. We demonstrate that Id1
      expression correlates with loss of p16/Ink4a expression in melanoma in situ;
      however, more advanced stages of melanoma do not express Id1 except within
      perivascular regions, despite overall decreased p16/Ink4a expression in these
      lesions. Microdissected lesions were evaluated for p16/Ink4a sequence, and
      invasive melanomas that did not express Id1 were found to have sustained
      inactivating p16/ink4a mutations. These data suggest a role for Id1 in regulating
      p16/Ink4a expression in early melanomas and demonstrate that later genetic
      changes may provide for irreversible loss of p16 expression in advanced stages of
      this tumor.

PMID- 11507044
TI  - A conditional replication-competent adenoviral vector, Ad-OC-E1a, to cotarget
      prostate cancer and bone stroma in an experimental model of androgen-independent
      prostate cancer bone metastasis.
AB  - Prostate cancer has a high propensity to metastasize to bone, which often resists
      hormone, radiation, and chemotherapies. Because of the reciprocal nature of the
      prostate cancer and bone stroma interaction, we designed a cotargeting strategy
      using a conditional replication-competent adenovirus to target the growth of
      tumor cells and their associated osteoblasts. The recombinant Ad-OC-E1a was
      constructed using a noncollagenous bone matrix protein osteocalcin (OC) promoter
      to drive the viral early E1a gene with restricted replication in cells that
      express OC transcriptional activity. Unlike Ad-PSE-E1a, Ad-OC-E1a was highly
      efficient in inhibiting the growth of PSA-producing (LNCaP, C4-2, and ARCaP) and
      nonproducing (PC-3 and DU145) human prostate cancer cell lines. This virus was
      also found to effectively inhibit the growth of human osteoblasts and human
      prostate stromal cells in vitro. Athymic mice bearing s.c. androgen receptor
      negative and PSA-negative PC-3 xenografts responded to a single intratumoral
      administration of 2 x 10(9) plaque-forming unit(s) of Ad-OC-E1a. In SCID/bg mice,
      intraosseous growth of androgen receptor-positive and PSA-producing C4-2
      xenografts responded markedly to i.v. administrations of a single dose of Ad-OC
      E1a. One hundred percent of the treated mice responded to this systemic Ad-OC-E1a
      therapy with a decline of serum PSA to an undetectable level, and 80% of the mice
      with PSA rebound responded to the second dose of systemic Ad-OC-E1a. Forty
      percent of the mice were found to be cured by systemic Ad-OC-E1a without
      subsequent PSA rebound or tumor cells found in the skeleton. This cotargeting
      strategy shows a broader spectrum and appears to be more effective than systemic
      Ad-PSE-E1a in preclinical models of human prostate cancer skeletal metastasis.

PMID- 11507045
TI  - Hypoxia and acidosis independently up-regulate vascular endothelial growth factor
      transcription in brain tumors in vivo.
AB  - Hypoxia and acidosis are hallmarks of tumors as well as critical determinants of
      response to treatments. They can upregulate vascular endothelial growth factor
      (VEGF) in vitro. However, the relationship between tissue oxygen partial pressure
      (pO(2))/pH and VEGF transcription in vivo is not known. Thus, we developed a
      novel in vivo microscopy technique to simultaneously measure VEGF promoter
      activity, pO(2), and pH. To monitor VEGF expression in vivo, we engineered human
      glioma cells that express green fluorescent protein (GFP) under the control of
      the VEGF promoter. These cells were implanted into the cranial windows in severe
      combined immunodeficient mice, and VEGF promoter activity was assessed by GFP
      imaging. Tissue pO(2) and pH were determined by phosphorescence quenching
      microscopy and ratio imaging microscopy, respectively. These techniques have
      allowed us to show, for the first time, that VEGF transcription in brain tumors
      is independently regulated by the tissue pO(2) and pH. One week after tumor
      implantation, significant angiogenesis was observed, with increased GFP
      fluorescence throughout the tumor. Under hypoxic or neutral pH conditions, VEGF
      promoter activity increased, with a decrease in pO(2) and independent of pH.
      Under low pH or oxygenated conditions, VEGF-promoter activity increased, with a
      decrease in pH and independent of pO(2). In agreement with the in vivo findings,
      both hypoxia and acidic pH induced VEGF expression in these cells in vitro and
      showed no additive effect for combined hypoxia and low pH. These results suggest
      that VEGF transcription in brain tumors is regulated by both tissue pO(2) and pH
      via distinct pathways.

PMID- 11507046
TI  - Age-related radical-induced DNA damage is linked to prostate cancer.
AB  - We measured concentrations and ratios of mutagenic (8-OH) lesions to putatively
      nonmutagenic formamidopyrimidine (Fapy) lesions of adenine (Ade) and guanine
      (Gua) to elucidate radical (.OH)-induced changes in DNA of normal, normal from
      cancer, and cancer tissues of the prostate. The relationship between the lesions
      was expressed using the mathematical model log(10)[(8-OH-Ade + 8-OH-Gua)/(FapyAde
      + FapyGua)]. Logistic regression analysis of the log ratios for DNA of normal and
      cancer tissues discriminated between the two tissue groups with high sensitivity
      and specificity. Correlation analysis of log ratios for normal prostates revealed
      a highly significant increase in the proportion of mutagenic base lesions with
      age. Data from correlation analysis of the log ratios for normal tissues from
      cancer were consistent with an age-dependent, dose-response relationship. The
      slopes for both correlations intersected at approximately 61 years, an age when
      prostate cancer incidence is known to rise sharply. The age-related increase in
      the proportion of.OH-induced mutagenic base lesions is likely a significant
      factor in prostate cancer development.

PMID- 11507047
TI  - Quantitation of serum prostate-specific membrane antigen by a novel protein
      biochip immunoassay discriminates benign from malignant prostate disease.
AB  - The lack of a sensitive immunoassay for quantitating serum prostate-specific
      membrane antigen (PSMA) hinders its clinical utility as a diagnostic/prognostic
      biomarker. An innovative protein biochip immunoassay was used to quantitate and
      compare serum PSMA levels in healthy men and patients with either benign or
      malignant prostate disease. PSMA was captured from serum by anti-PSMA antibody
      bound to ProteinChip arrays, the captured PSMA detected by surface-enhanced laser
      desorption/ionization mass spectrometry, and quantitated by comparing the mass
      signal integrals to a standard curve established using purified recombinant PSMA.
      The average serum PSMA value for prostate cancer (623.1 ng/ml) was significantly
      different (P < 0.001) from that for benign prostate hyperplasia (117.1 ng/ml) and
      the normal groups (age <50, 272.9 ng/ml; age >50, 359.4 ng/ml). These initial
      results suggest that serum PSMA may be a more effective biomarker than prostate
      specific antigen for differentiating benign from malignant prostate disease and
      warrants additional evaluation of the surface-enhanced laser
      desorption/ionization PSMA immunoassay to determine its diagnostic utility.

PMID- 11507048
TI  - A novel 7-modified camptothecin analog overcomes breast cancer resistance protein
      associated resistance in a mitoxantrone-selected colon carcinoma cell line.
AB  - We selected a mitoxantrone-resistant HT29 colon carcinoma cell line (HT29/MIT)
      that exhibited a very high degree of resistance to the selecting agent and marked
      resistance to topotecan and SN38, but limited resistance to doxorubicin. The
      development of drug resistance was independent of expression of P-glycoprotein or
      multidrug resistance-associated protein but was associated with high up
      regulation of the breast carcinoma resistance protein (BCRP) as shown by Western
      blot analysis. BCRP overexpression was associated with a reduced intracellular
      accumulation of topotecan, a known substrate for BCRP. Conversely, a lipophilic 7
      modified camptothecin analogue (ST1481) displayed a complete lack of cross
      resistance in HT29/MIT cells, suggesting that the drug was not a substrate for
      BCRP because no defects in intracellular accumulation were found. This conclusion
      is consistent with the antitumor efficacy of ST1481 against a BCRP-expressing
      tumor. These results may have therapeutic implications because the antitumor
      efficacy of ST1481 is in part related to a good bioavailability after oral
      administration, and the drug is currently under Phase I clinical evaluation.

PMID- 11507049
TI  - ELAC2/HPC2 involvement in hereditary and sporadic prostate cancer.
AB  - The ELAC2/HPC2 gene at 17p11 is the first candidate gene identified for human
      prostate cancer (PRCA) based on linkage analysis and positional cloning (S. V.
      Tavtigian et al. Nat. Genet., 27:172-180, 2001). A truncating mutation was found
      in one hereditary prostate cancer (HPC) family, whereas two missense variants,
      Ser217Leu and Ala541Thr, were reported to be associated with increased PRCA risk
      in the general population. Here, we screened for mutations of the ELAC2/HPC2 gene
      in 66 Finnish HPC families. Several sequence variants, including a new exonic
      variant (Glu622Val) were found, but none of the mutations were truncating. We
      then analyzed the frequency of the three found missense variants in 1365
      individuals, including hereditary (n = 107) and unselected (n = 467) PRCA, benign
      prostatic hyperplasia (n = 223), and population controls (568 healthy male blood
      donors). Ser217Leu and Ala541Thr variants carried no significantly elevated risk
      for HPC or PRCA, although the latter variant was associated with benign prostatic
      hyperplasia. The previously undescribed Glu622Val variant had a 1.0% population
      prevalence, but a significantly higher frequency in PRCA cases (3.0% odds ratio,
      2.94; 95% confidence interval, 1.05-8.23). We conclude that ELAC2/HPC2 truncating
      mutations are rare in HPC, but that rare variants of the ELAC2/HPC2 require
      additional study as risk factors for PRCA in the general population.

PMID- 11507050
TI  - CYCLIN D1 as a genetic modifier in hereditary nonpolyposis colorectal cancer.
AB  - Hereditary nonpolyposis colorectal cancer is associated with inherited defects in
      DNA mismatch repair. Clinical variation even in cases with identical predisposing
      mutations suggests the existence of other factors contributing to the phenotype.
      We addressed the modifying role of the common A/G polymorphism in exon 4 and the
      alternatively spliced transcripts a and b of the CCND1 gene encoding cyclin D1 in
      a series of 146 affected carriers of 10 MLH1 and 3 MSH2 mutations. No correlation
      was observed between a particular allele (A versus G) and age at onset. However,
      the presence of the variant transcript b in blood/normal mucosa, by multiplex
      reverse transcription-PCR, was associated with a significantly lower age at onset
      of colon cancer as compared with individuals with transcript a only (35 versus 46
      years; P = 0.02). Whereas our data do not support a modifying role of A versus G
      allele of CCND1, the results do suggest that the relative abundance of a and b
      transcripts may modify the age at onset of colon cancer in hereditary
      nonpolyposis colorectal cancer.

PMID- 11507051
TI  - Instabilotyping: comprehensive identification of frameshift mutations caused by
      coding region microsatellite instability.
AB  - Coding region frameshift mutation caused by microsatellite instability (MSI) is
      one mechanism contributing to tumorigenesis in cancers with MSI in high
      frequency. Mutation of TGFBR2 is one example of this process. To identify
      additional examples, a large-scale genomic screen of coding region
      microsatellites was conducted. 1115 coding homopolymeric loci with six or more
      nucleotides were identified in an online genetic database. Mutational screening
      was performed at 152 of these loci in 46 colorectal tumors with MSI in high
      frequency. Nine loci were mutated in > or =20% of tumors, 10 loci in 10-20%, 24
      loci in 5-10%, 43 loci in <5%, and 66 loci were not mutated in any tumors. The
      most frequently mutated novel loci were the activin type II receptor gene
      (58.1%), SEC63 (48.8%), AIM 2 (47.6%), a gene encoding a subunit of the NADH
      ubiquinone oxidoreductase complex (27.9%), a homologue of mouse cordon-bleu
      (23.8%), and EBP1/PA2G4 (20.9%). This genome-wide approach identifies coding
      region MSI in genes or pathways not implicated previously in colorectal
      tumorigenesis, which may merit functional study or other additional analysis.

PMID- 11507052
TI  - Regulation of vascular endothelial growth factor by the Wnt and K-ras pathways in
      colonic neoplasia.
AB  - Angiogenesis is not restricted to advanced stages of tumor development but is
      also observed in benign precursor lesions. Vascular endothelial growth factor
      (VEGF) is a key regulator of tumor angiogenesis, but the genetic mechanisms
      controlling its expression in premalignant lesions are poorly described. The Wnt
      signaling pathway, which is commonly mutated in benign colonic adenomas, was
      found to strongly up-regulate VEGF. A T-cell factor-4-binding element at -805 bp
      in the VEGF promoter is an important mediator of this effect. Signaling through
      the K-ras oncogene, also frequently mutated in benign colonic polyps, up
      regulated VEGF in a phosphatidylinositol 3-kinase-dependent manner. Furthermore,
      K-ras activation appeared to enhance Wnt signaling, which suggests a unique
      interaction between these two pathways. These studies thus identify VEGF as a
      novel target of the Wnt pathway in early colonic neoplasia and serve to
      underscore the importance of angiogenesis in premalignant disease.

PMID- 11507053
TI  - The expression of inducible cAMP early repressor (ICER) is altered in prostate
      cancer cells and reverses the transformed phenotype of the LNCaP prostate tumor
      cell line.
AB  - Inducible cAMP early repressor (ICER) has been shown to be an important mediator
      of cAMP antiproliferative activity. In this report, it was found that cAMP
      retards LNCaP cell growth; in contrast, cAMP inhibits the growth of PC-3 and DU
      145 cells. ICER protein levels were markedly reduced in prostate cancer
      epithelial cells and undetectable and uninducible by cAMP in LNCaP and DU 145
      cells. Forced expression of ICER in LNCaP cells caused inhibition of cell growth
      and thymidine incorporation and halted cells at the G(1) phase of the cell cycle.
      These ICER-bearing LNCaP cells were rendered unable to grow in soft agar and
      unable to form tumors in nude mice. These results suggest that deregulation of
      ICER expression may be related to carcinogenesis of the prostate gland.

PMID- 11507054
TI  - Phosphorylation of mitogen-activated protein kinase is inhibited by calcitonin in
      DU145 prostate cancer cells.
AB  - One of the causes of insensitivity to androgen ablation therapy in prostate
      cancer is thought to be attributable to elevated neuropeptides secreted by
      neuroendocrine cells in the tumor mass. Calcitonin (CT), one of these
      neuropeptides, is reported to be associated with the growth of prostate cancer.
      There is an increase in mitogen-activated protein (MAP) kinase activation as
      prostate cancer progresses to a more advanced and androgen-independent disease.
      We examined the effect of CT on signal transduction and the relation between CT
      and early-response genes in the human androgen-insensitive prostate cancer cell
      line, DU145. The basal phosphorylation level of extracellular signal-regulated
      kinase 1/2, which is a key kinase in the mediation of growth factor-induced
      mitogenesis in prostate cancer cells, was constitutively up-regulated. N-[2-(4
      bromocinnamyl) aminoethyl]-5-isoquinoline-sulfonamide (H89), a specific inhibitor
      of protein kinase A, potentiated the effects of more increased phosphorylation of
      extracellular signal-regulated kinase 1/2. CT induced the inhibition of this MAP
      kinase phosphorylation, and this effect was completely abolished by pretreatment
      with H89. Our findings demonstrate that CT caused the inhibition of constitutive
      MAP kinase phosphorylation in a protein kinase A-dependent manner in DU145. The
      transient increase of c-fos expression was detected after CT treatment, whereas
      expression of c-jun RNA was down-regulated after CT treatment. These results
      suggest that CT may regulate early-response genes, c-fos and c-jun, via a MAP
      kinase cascade. In conclusion, these findings suggest that DU145 might be a
      useful model as a therapeutic approach of neuropeptides in androgen-independent
      prostatic carcinoma.

PMID- 11507055
TI  - A human prostatic epithelial model of hormonal carcinogenesis.
AB  - The effects of stromal and hormonal environment on the immortalized but
      nontumorigenic human prostatic epithelial cell line BPH-1 were investigated in an
      in vivo model. BPH-1 cells were recombined with rat urogenital sinus mesenchyme
      (UGM), and the tissue recombinants were grafted to the renal capsule of adult
      male athymic mouse hosts. BPH-1 + UGM recombinants formed solid branching
      epithelial cords with a well-defined basement membrane. The cords canalized to
      form ductal structures. The mesenchymal cells formed thick sheets of well
      differentiated smooth muscle surrounding the epithelium, reinforcing the idea
      that the epithelium dictates the patterning of prostatic stromal cells. When
      hosts carrying BPH-1 + UGM tissue recombinants were exposed to testosterone
      propionate and 17-beta-estradiol (T + E2), the tissue recombinants responded by
      forming invasive carcinomas, demonstrating mixed, predominantly squamous as well
      as adenocarcinomatous (small acinar and mucinous) differentiation. When either
      untreated or T + E2-treated hosts were castrated, epithelial apoptosis was
      observed in the grafts. When tumors were removed and regrafted to fresh hosts
      they grew rapidly. Tumors were serially regrafted through six generations.
      Histologically these tumors consisted largely of focally keratinizing squamous
      cell carcinoma with high-grade malignant cytological features. BPH-1 cells grown
      in the absence of UGM survived at the graft site but did not form tumors or
      organized structures. This behavior was not influenced by the presence or absence
      of T + E2 stimulation. These data show that an immortalized, nontumorigenic human
      prostatic epithelial cell line can undergo hormonal carcinogenesis in response to
      T + E2 stimulation. In addition, the data demonstrate that the stromal
      environment plays an important role in mediating hormonal carcinogenesis.

PMID- 11507056
TI  - Targeted antizyme expression in the skin of transgenic mice reduces tumor
      promoter induction of ornithine decarboxylase and decreases sensitivity to
      chemical carcinogenesis.
AB  - To directly evaluate the role of increased ornithine decarboxylase (ODC) and
      polyamines in mouse skin carcinogenesis, we used bovine keratin 5 (K5) and
      keratin 6 (K6) promoter elements to direct the expression of antizyme (AZ) to
      specific skin cell populations. AZ is a multifunctional regulator of polyamine
      metabolism that inhibits ODC activity, stimulates ODC degradation, and suppresses
      polyamine uptake. K5-AZ mice treated with 12-O-tetradecanoylphorbol-13-acetate
      (TPA) at 0 and 24 h exhibit increases in epidermal and dermal ODC activity that
      are reduced in magnitude. K6-AZ mice treated similarly do not show any increased
      ODC activity or protein after a second application due to TPA-induced expression
      of AZ protein. Epidermal and dermal polyamine content, particularly spermidine,
      is reduced in untreated K5-AZ mice and TPA-treated K5-AZ and K6-AZ mice.
      Susceptibility to 7,12-dimethylbenz(a)anthracene/TPA carcinogenesis was also
      investigated for two K6-AZ transgenic lines [K6-AZ(52) and K6-AZ(18)] and a
      single K5-AZ line. K6-AZ(52) mice had a substantial delay in tumor onset and a
      >80% reduction in tumor multiplicity compared with normal littermates. K6-AZ(18)
      and K5-AZ mice also developed fewer papillomas than littermate controls (35% and
      50%, respectively), and the combination of these lines to produce double
      transgenic animals yielded an additive decrease (70%) in tumor multiplicity.
      These mice demonstrate for the first time that AZ suppresses tumor growth in an
      animal cancer model and provide a valuable model system to evaluate the role of
      ODC and polyamines in skin tumorigenesis.

PMID- 11507057
TI  - Overexpression of manganese superoxide dismutase suppresses tumor formation by
      modulation of activator protein-1 signaling in a multistage skin carcinogenesis
      model.
AB  - Manganese superoxide dismutase (MnSOD) is a nuclear encoded primary antioxidant
      enzyme localized in mitochondria. Because expression of MnSOD plays a major role
      in maintaining cellular redox status and reactive oxygen species are known to
      play a role in signal transduction and carcinogenesis, we investigated the role
      of MnSOD in the development of cancer using a two-stage [7,12-dimethylbenz(a)
      anthracene plus 12-O-tetradecanoylphorbol-13-acetate (TPA)] skin carcinogenesis
      model. Female transgenic mice expressing the human MnSOD gene in the skin and
      their nontransgenic counterparts were used in this study. Pathological
      examination demonstrated significant reduction of papilloma formation in
      transgenic mice. Quantitative analysis of 4-hydroxy-2-nonenal-modified proteins
      showed greater accumulation of oxidative damage products in nontransgenic
      compared with transgenic mice, and this oxidative damage was demonstrated to be
      present in both mitochondria and nucleus. TPA increased activator protein-1 (AP
      1) binding activity within 6 h in nontransgenic mice, but increased AP-1 binding
      activity was delayed in the transgenic mice. Electrophoretic mobility shift
      assay, transcription of the target genes, and Western analysis studies indicated
      that the increased AP-1 binding activity was attributable to induction of the Jun
      but not the Fos protein families. Overexpression of MnSOD selectively inhibited
      the TPA-induced activation of protein kinase Cepsilon and prevented subsequent
      activation of c-Jun NH(2)-terminal kinase in response to TPA. Overall, these
      results indicate that MnSOD regulates both cellular redox status and selectively
      modulates PKCepsilon signaling, thereby delaying AP-1 activation and inhibiting
      tumor promotion, resulting in reduction of tumors in MnSOD transgenic mice.

PMID- 11507058
TI  - Estrogen imprinting of the developing prostate gland is mediated through stromal
      estrogen receptor alpha: studies with alphaERKO and betaERKO mice.
AB  - Neonatal exposure of rodents to high doses of estrogen permanently imprints the
      growth and function of the prostate and predisposes this gland to hyperplasia and
      severe dysplasia analogous to prostatic intraepithelial neoplasia with aging.
      Because the rodent prostate gland expresses estrogen receptor (ER)-alpha within a
      subpopulation of stromal cells and ERbeta within epithelial cells, the present
      study was undertaken to determine the specific ER(s) involved in mediating
      prostatic developmental estrogenization. Wild-type (WT) mice, homozygous mutant
      ER (ERKO) alpha -/- mice, and betaERKO -/- mice were injected with 2 microg of
      diethylstilbestrol (DES) or oil (controls) on days 1, 3, and 5 of life.
      Reproductive tracts were excised on days 5 or 10 (prepubertal), day 30
      (pubertal), day 90 (young adult), or with aging at 6, 12, and 18 months of age.
      Prostate complexes were microdissected and examined histologically for prostatic
      lesions and markers of estrogenization. Immunocytochemistry was used to examine
      expression of androgen receptor, ERalpha, ERbeta, cytokeratin 14 (basal cells),
      cytokeratin 18 (luminal cells), and dorsolateral protein over time in the treated
      mice. In WT-DES mice, developmental estrogenization of the prostate was observed
      at all of the time points as compared with WT-oil mice. These prostatic imprints
      included transient up-regulation of ERalpha, down-regulation of androgen
      receptor, decreased ERbeta levels in adult prostate epithelium, lack of DLP
      secretory protein, and a continuous layer of basal cells lining the ducts. With
      aging, epithelial dysplasia and inflammatory cell infiltrate were observed in the
      ventral and dorsolateral prostate lobes. In contrast, the prostates of alphaERKO
      mice exhibited no response to neonatal DES either immediately after exposure or
      throughout life up to 18 months of age. Furthermore, neonatal DES treatment of
      betaERKO mice resulted in a prostatic response similar to that observed in WT
      animals. The present findings indicate that ERalpha is the dominant ER form
      mediating the developmental estrogenization of the prostate gland. If epithelial
      ERbeta is involved in some component of estrogen imprinting, its role would be
      considered minor and would require the presence of ERalpha expression in the
      prostatic stromal cells.

PMID- 11507059
TI  - A molecular mimic of phosphorylated prolactin markedly reduced tumor incidence
      and size when DU145 human prostate cancer cells were grown in nude mice.
AB  - Others have demonstrated the presence of an autocrine prolactin (PRL) growth loop
      in the normal human prostate. In this study we have used three human prostate
      cancer cell lines but have focused on the androgen-independent human prostate
      cancer cell line, DU145, to ask: (a) whether this autocrine growth loop is
      maintained beyond the loss of androgen sensitivity in the progression of prostate
      cancer; and (b) whether interruption of this growth loop by a PRL receptor
      antagonist, an S179D mutant PRL, could inhibit the formation of DU145-derived
      tumors. The autocrine loop was examined in most detail in the DU145 cell line but
      was demonstrated to be functional in all three of the lines by the reversible
      inhibition of growth in vitro by the S179D PRL receptor antagonist. To
      investigate the effect of S179D PRL on the growth of DU145 tumors in nude mice
      two sets of experiments were performed. In the first set, Alzet minipumps
      containing no PRL, wild-type (WT) PRL, or the S179D PRL (the last two delivering
      4.56 microg/24 h and 4.26 microg/24 h, respectively), were implanted s.c. on day
      1. On day 4, 5 x 10(6) DU145 cells were injected s.c. in the hindquarter. On day
      22, the animals were killed, tumors were removed, measured, and subsequently
      fixed and processed for histological confirmation of tumor formation. The
      incidence of tumors in the no-PRL control group was 9/11 animals (82%). In the
      animals treated with WT PRL, the incidence was 8/10 (80%), whereas in the animals
      treated with the S179D PRL, the incidence was markedly reduced to 3/11 (27%).
      Although WT PRL had no effect on the incidence of tumors, the average size of the
      tumors increased from 25.8 +/- 5.99 mm(3) in controls to 66.66 +/- 18.06 mm(3) in
      WT PRL-treated animals. In the second set of experiments, 5 x 10(6) DU145 cells
      were injected on day 1. On day 18, Alzet minipumps containing no PRL, WT PRL, or
      S179D PRL were implanted. On day 42, the animals were killed and the tumors
      processed as before. S179D PRL caused a reduction in tumor size from 1731 +/- 283
      mm(3) in the no-PRL controls to 1031 +/- 295 mm(3), whereas WT PRL slightly
      increased the size to 2118 +/- 630 mm(3). We conclude that PRL is used as an
      autocrine growth factor by human prostate cancer cells both in vitro and in vivo
      and that interruption of this growth loop in vivo inhibits tumor initiation and
      the growth of well-established tumors.

PMID- 11507060
TI  - Overexpression and overactivation of Akt in thyroid carcinoma.
AB  - Enhanced activation of Akt occurs in Cowden's disease, an inherited syndrome of
      follicular thyroid, breast, colon, and skin tumors, via inactivation of its
      regulatory protein, PTEN. Whereas PTEN inactivation is uncommon in sporadic
      thyroid cancer, activation of growth factor pathways that signal through Akt is
      frequently identified. We hypothesized that Akt overactivation could be a common
      finding in sporadic thyroid cancer and might be important in thyroid cancer
      biology. We examined thyroid cancer cells lines and benign and malignant thyroid
      tissue for total Akt activation and isoform-specific Akt expression. In thyroid
      cancer cells, Akt 1, 2, and 3 proteins were expressed, total Akt was activated by
      insulin phosphatidylinositol 3'-kinase, and inhibition of phosphatidylinositol 3'
      kinase reduced cell viability. In human thyroid tissue, increased levels of
      phosphorylated total Akt were identified in follicular but not papillary cancers
      compared with normal tissue. Levels of Akt 1 and 2 proteins and Akt 2 RNA were
      elevated only in the follicular cancers. In paired samples, Akt 1, 2, 3, and
      phospho-Akt levels were higher in five of six cancers, including three of three
      follicular cancers. These data suggest that Akt activation may play a role in the
      pathogenesis or progression of sporadic thyroid cancer.

PMID- 11507061
TI  - Chemoprevention of esophageal tumorigenesis by dietary administration of
      lyophilized black raspberries.
AB  - Fruit and vegetable consumption has consistently been associated with decreased
      risk of a number of aerodigestive tract cancers, including esophageal cancer. We
      have taken a "food-based" chemopreventive approach to evaluate the inhibitory
      potential of lyophilized black raspberries (LBRs) against N
      nitrosomethylbenzylamine (NMBA)-induced esophageal tumorigenesis in the F344 rat,
      during initiation and postinitiation phases of carcinogenesis. Anti-initiation
      studies included a 30-week tumorigenicity bioassay, quantification of DNA
      adducts, and NMBA metabolism study. Feeding 5 and 10% LBRs, for 2 weeks prior to
      NMBA treatment (0.25 mg/kg, weekly for 15 weeks) and throughout a 30-week
      bioassay, significantly reduced tumor multiplicity (39 and 49%, respectively). In
      a short-term bioassay, 5 and 10% LBRs inhibited formation of the promutagenic
      adduct O(6)-methylguanine (O(6)-meGua) by 73 and 80%, respectively, after a
      single dose of NMBA at 0.25 mg/kg. Feeding 5% LBRs also significantly inhibited
      adduct formation (64%) after NMBA administration at 0.50 mg/kg. The
      postinitiation inhibitory potential of berries was evaluated in a second bioassay
      with sacrifices at 15, 25, and 35 weeks. Administration of LBRs began after NMBA
      treatment (0.25 mg/kg, three times per week for 5 weeks). LBRs inhibited tumor
      progression as evidenced by significant reductions in the formation of
      preneoplastic esophageal lesions, decreased tumor incidence and multiplicity, and
      reduced cellular proliferation. At 25 weeks, both 5 and 10% LBRs significantly
      reduced tumor incidence (54 and 46%, respectively), tumor multiplicity (62 and
      43%, respectively), proliferation rates, and preneoplastic lesion development.
      Yet, at 35 weeks, only 5% LBRs significantly reduced tumor incidence and
      multiplicity, proliferation indices and preneoplastic lesion formation. In
      conclusion, dietary administration of LBRs inhibited events associated with both
      the initiation and promotion/progression stages of carcinogenesis, which is
      promising considering the limited number of chemopreventives with this potential.

PMID- 11507062
TI  - Dietary indoles and isothiocyanates that are generated from cruciferous
      vegetables can both stimulate apoptosis and confer protection against DNA damage
      in human colon cell lines.
AB  - The natural indoles 3,3'-diindolylmethane (DIM), ascorbigen (ASG), indole-3
      carbinol (I3C), and indolo[3,2-b]carbazole (ICZ), as well as the natural
      isothiocyanates sulforaphane (SUL), benzyl isothiocyanate (BITC) and phenethyl
      isothiocyanate (PEITC), all possess cancer chemopreventive properties. It is now
      shown that DIM, ICZ, SUL, and BITC can each stimulate apoptosis in human colon
      adenocarcinoma LS-174 and Caco-2 cells. Treatment of LS-174 cells with nontoxic
      doses of DIM, ASG, I3C, or ICZ affected an increase of up to 21-fold in
      cytochrome P450 1A1 (CYP1A1). None of these indoles caused an elevation in either
      aldo-keto reductase 1C1 (AKR1C1) or the gamma-glutamylcysteine synthetase heavy
      subunit (GCS(h)), but DIM, I3C, and ICZ produced a very modest increase in
      NAD(P)H:quinone oxidoreductase 1 (NQO1). By contrast, nontoxic doses of SUL,
      BITC, or PEITC failed to induce expression of CYP1A1 in LS-174 cells, but caused
      an increase of between 11- and 17-fold in the protein levels of AKR1C1, NQO1, and
      GCS(h). Treatment of the colon cell line with ICZ or SUL caused increases in the
      levels of mRNA for CYP1A1, AKR1C1, and NQO1 that were consistent with the enzyme
      data. Exposure of Caco-2 cells to media containing indoles or isothiocyanates
      gave similar results to those obtained using LS-174 cells. Evidence is presented
      that the ability of indoles and isothiocyanates to stimulate either xenobiotic
      response element- or antioxidant response element-driven gene expression accounts
      for the two groups of phytochemicals inducing different gene batteries.
      Pretreatment of LS-174 cells for 24 h with ICZ and SUL before exposure for 24 h
      to benzo(a)pyrene (BaP) reduced to <20% the number of single-strand DNA breaks
      produced by the carcinogen. Neither ICZ alone nor SUL alone were able to confer
      the same degree of protection against DNA damage produced by BaP as they achieved
      in combination. Similar results were obtained with H(2)O(2) as the genotoxic
      agent. Together, these phytochemicals may prevent colon tumorigenesis by both
      stimulating apoptosis and enhancing intracellular defenses against genotoxic
      agents.

PMID- 11507063
TI  - Suppression of intestinal polyps in Msh2-deficient and non-Msh2-deficient
      multiple intestinal neoplasia mice by a specific cyclooxygenase-2 inhibitor and
      by a dual cyclooxygenase-1/2 inhibitor.
AB  - Epidemiological studies suggest that nonsteroidal anti-inflammatory agents
      decrease the risk of colorectal cancer. This is believed to be mediated, at least
      in part, by inhibition of cyclooxygenase (COX) activity. There are two COX
      isoenzymes, namely the constitutively expressed COX-1 and the inducible COX-2.
      COX-2 is overexpressed in adenomas and colorectal cancers, and COX-2-specific
      inhibitors have been shown to inhibit intestinal polyps in Apc(Delta716) mice
      more effectively than dual COX-1/COX-2 inhibitors such as sulindac. Various Apc
      knockout mice, including the multiple intestinal neoplasia (Min) mouse and the
      Apc(Delta716) mouse, are limited by their lack of large numbers of colonic
      adenomas and aberrant crypt foci, the putative precursors of large-bowel polyps
      and cancers. Our DNA mismatch-repair-deficient Min mouse model (Apc+/-Msh2-/-)
      has genetic features of both familial adenomatous polyposis and hereditary
      nonpolyposis colorectal cancer, and most importantly, rapidly develops numerous
      small- and large-bowel adenomas, as well as colonic aberrant crypt foci. The
      purpose of this study was to determine the effects of COX inhibitors on
      intestinal adenomas and colonic aberrant crypt foci in this accelerated
      polyposis, mismatch-repair-deficient Min mouse model, in addition to a standard
      Min mouse model. Weanling Apc+/-Msh2-/- and Min mice were fed diets containing no
      drug, sulindac, or a specific COX-2 inhibitor (MF-tricyclic). Apc+/-Msh2-/- and
      Min mice were sacrificed after 4 weeks and 5 months on diet, respectively. Apc+/
      Msh2-/- mice treated with MF-tricyclic had significantly fewer small-bowel polyps
      (mean +/- SD, 178 +/- 29) compared with mice on sulindac (278 +/- 80), or control
      diet (341 +/- 43; P < 0.001). There was no difference in numbers of large-bowel
      polyps or aberrant crypt foci in mice in the three groups. MF-tricyclic was also
      effective in reducing both small- and large-bowel polyps in Min mice. Western
      analysis demonstrated COX-2 expression in both large- and small-bowel polyps from
      mice of both genotypes. This study demonstrates that a specific COX-2 inhibitor
      is effective in preventing small-bowel polyps in mismatch-repair-deficient Min
      mice and both small- and large-bowel polyps in standard Min mice. Therefore,
      specific COX-2 inhibitors may be useful as chemopreventive and therapeutic agents
      in humans at risk for colorectal neoplasia.

PMID- 11507065
TI  - Nontoxic doses of suramin enhance activity of paclitaxel against lung metastases.
AB  - We recently reported that acidic (aFGF) and basic (bFGF) fibroblast growth
      factors confer a broad spectrum chemoresistance in solid tumors, and that
      suramin, an inhibitor of multiple growth factors including aFGF and bFGF,
      enhanced the in vitro antitumor activity of several anticancer drugs including
      paclitaxel (Song, S., et al., Proc. Natl. Acad. Sci. USA, 97: 8658-8663, 2000).
      The present study investigated in vitro and in vivo interaction between
      paclitaxel and suramin, using human PC3-LN cells which, upon i.v. injection into
      immunodeficient mice, yielded lung metastases in 100% of animals. In in vitro
      studies, conditioned medium (CM) obtained from histocultures of rat lung
      metastases induced a 3-fold resistance. The addition of suramin had no effect in
      the absence of CM but reversed the CM-induced resistance; calculations based on
      the IC(50) values indicate a complete reversal in the presence of <20 microM
      suramin. Analysis by the combination index method indicates a synergistic
      interaction between paclitaxel and suramin. In in vivo studies, animals with well
      established lung metastases (at least five nodules of 1 mm in diameter) were
      treated i.v. with paclitaxel (15 mg/kg) and suramin (10 mg/kg) administered twice
      weekly for 3 weeks. Single-drug therapy with paclitaxel or suramin did not reduce
      body weight. Suramin alone had no antitumor activity. Paclitaxel alone reduced
      the tumor size by approximately 75%, reduced the density of nonapoptotic cells by
      approximately 70% in residual tumors, and enhanced the fraction of apoptotic
      cells by approximately 3-fold. The addition of suramin to paclitaxel therapy
      enhanced the antitumor effect, resulting in an additional 5-fold reduction of
      tumor size, an additional 9-fold reduction of the density of nonapoptotic cells,
      and an additional 30% increase in the apoptotic cell fraction. These data
      indicate significant enhancement of the efficacy of paclitaxel by suramin and
      support the use of nontoxic doses of suramin with paclitaxel in the treatment of
      lung cancer.

PMID- 11507064
TI  - Resveratrol exhibits cytostatic and antiestrogenic properties with human
      endometrial adenocarcinoma (Ishikawa) cells.
AB  - Trans-3,4',5-trihydroxystilbene (resveratrol), a polyphenolic compound found in
      the human diet, was reported recently to serve as an estrogen agonist with
      cultured MCF-7 cells transfected with estrogen response element-luciferase
      reporter plasmids. As currently shown, treatment of cultured human endometrial
      adenocarcinoma (Ishikawa) cells with resveratrol (concentrations as high as 10
      microM) did not significantly increase the levels of an estrogen-inducible marker
      enzyme, alkaline phosphatase. To the contrary, when alkaline phosphatase was
      induced by treatment with 1 nM of 17beta-estradiol (E(2)), resveratrol exhibited
      a dose-dependent decrease in activity (IC(50) = 2.3 microM). Furthermore, when
      Ishikawa cells were treated with resveratrol as a single agent, estrogen
      inducible progesterone receptor (PR) was not enhanced, and PR expression induced
      by treatment with E(2) was inhibited by resveratrol in a dose-dependent fashion
      at both the mRNA and protein levels. In addition, resveratrol mediated
      suppression of a functional activity of PR as demonstrated by down-regulation of
      alpha(1)-integrin expression induced by E(2) plus progesterone. With transient
      transfection experiments conducted with Ishikawa cells, antiestrogenic effects
      were confirmed by dose-dependent inhibition of E(2)-induced estrogen response
      element-luciferase transcriptional activity. Because resveratrol antagonized
      estrogenic effects in Ishikawa cells, competitive binding analyses were performed
      to examine the potential of displacing [(3)H]E(2) from human estrogen receptor
      (ER). Resveratrol showed no discernable activity with ER-alpha, but with ER-beta,
      E(2) was displaced with an IC(50) of 125 microM. However, mRNA and protein
      expression of ER-alpha but not ER-beta were suppressed by resveratrol in Ishikawa
      cells, in the concentration range of 5-15 microM. In addition, in the presence or
      absence of E(2), resveratrol inhibited Ishikawa cell proliferation in a time
      dependent manner with cells accumulating in the S phase of the cycle < or =48 h.
      This effect was reversible. Analysis of some critical cell cycle proteins
      revealed a specific increase in expression of cyclins A and E but a decrease in
      cyclin-dependent kinase 2. These data suggest resveratrol exerts an
      antiproliferative effect in Ishikawa cells, and the effect may be mediated by
      both estrogen-dependent and -independent mechanisms.

PMID- 11507066
TI  - Growth-inhibitory effect of a streptococcal antitumor glycoprotein on human
      epidermoid carcinoma A431 cells: involvement of dephosphorylation of epidermal
      growth factor receptor.
AB  - An antitumor glycoprotein [streptococcal acidic glycoprotein (SAGP)] purified
      from an extract of Streptococcus pyogenes inhibited the growth of human
      epidermoid carcinoma A431 cells overexpressing epidermal growth factor receptor
      (EGFR) in a time- and a concentration-dependent manner. The antiproliferative
      effect of SAGP was diminished by preincubating the cells with pertussis toxin and
      by coadministration of sodium orthovanadate, an inhibitor of protein tyrosine
      phosphatases (PTPases). Western blot analysis showed that the immunoreactivity of
      a M(r) 170,000 band of cell lysate to antiphosphotyrosine antibody was reduced by
      SAGP, and the effect was abolished by sodium orthovanadate. The phosphotyrosine
      level of the precipitant with anti-EGFR antibody was reduced by SAGP, which was
      abolished by preincubation with pertussis toxin or by a coadministration with
      sodium orthovanadate. The PTPase activity transiently increased in the lysate of
      cells incubated with SAGP and was inhibitable by sodium orthovanadate.
      Additionally, preincubation of serum-starved A431 cells with SAGP decreased the
      epidermal growth factor-induced tyrosine phosphorylation of EGFR, and the effect
      of SAGP was sodium orthovanadate sensitive. These findings indicate that
      dephosphorylation of the M(r) 170,000 EGFR by activation of PTPase(s) may be
      responsible in part for the antiproliferative effect of SAGP on A431 cells.

PMID- 11507067
TI  - Carcinoembryonic antigen-specific suicide gene therapy of cytosine deaminase/5
      fluorocytosine enhanced by the cre/loxP system in the orthotopic gastric
      carcinoma model.
AB  - Tumor-specific gene delivery is crucial to achieving successful effects in
      suicide gene therapy. Carcinoembryonic antigen (CEA) promoter has been widely
      used for this purpose, but the expression level of tumor-specific promoters such
      as CEA promoter is generally low. In the previous study, we used the Cre/loxP
      system and showed that LacZ expression by the CEA promoter was remarkably
      enhanced and maintained its specificity using the Cre/loxP regulation system. In
      this study, the Cre/loxP system was first applied to augmentation of selective
      expression of the cytosine deaminase (CD) gene as a suicide gene therapy in CEA
      producing cells. The double infection with AxCEANCre expressing Cre recombinase
      under the control of the CEA promoter and AxCALNLCD expressing the CD gene under
      the control of the CAG promoter by the Cre switching system rendered CEA
      producing tumor cells 13-fold more sensitive to 5-fluorocytosine (5-FC) compared
      with the single infection with AxCEACD expressing CD gene driven by the CEA
      promoter. The therapeutic efficacy of the enhanced CD/5-FC suicide gene therapy
      was evaluated in orthotopic implantation models of human gastric carcinoma.
      Adenovirus vectors (1 x 10(9) plaque-forming units) were administered i.p. into
      mice three times, and then 5-FC was administered i.p. for the next 10 days. Tumor
      volume and weight in mice treated with AxCEANCre and AxCALNLCD/5-FC were
      significantly reduced as compared with those in mice treated not only with Mock
      (AxCALacZ) but also with AxCEACD/5-FC (P < 0.0001). This beneficial effect on
      tumor burden was also reflected in the overall survival. The survival periods of
      the mice treated with AxCEANCre and AxCALNLCD/5-FC were longer than those of mice
      treated with Mock or AxCEACD/5-FC (P < 0.01). These results suggested that
      application of the Cre/loxP system could provide a new approach for enhanced
      selective suicide gene therapy of CD/5-FC for the treatment of advanced gastric
      carcinoma.

PMID- 11507068
TI  - An adenovirus expressing mutant p27 showed more potent antitumor effects than
      adenovirus-p27 wild type.
AB  - The main inhibitory action of p27, a cyclin-dependent kinase inhibitor (CDKI),
      arises from its binding with the cyclin E/cyclin-dependent kinase 2 (Cdk2)
      complex that results in G(1)-S arrest. Degradation of p27 is mediated by
      phosphorylation of Thr-187 of p27, which follows ubiquitination. In this study,
      we generated two adenoviruses expressing wild-type p27 (ad-p27wt) and mutant p27
      (ad-p27mt), with mutation of Thr-187/Pro-188 (ACGCCC) to Met-187/Ile-188
      (ATGATC), which was produced with the belief that mutant p27 would bind cyclin
      E/CDK2 more stably and show more potent antitumor effects. Ad-p27wt and ad-p27mt
      expressed p27 proteins that were indistinguishable by anti-p27 antibody. A pulse
      chase experiment showed that p27mt was more resistant to degradation than p27wt.
      In human lung cancer cell lines, ad-p27mt showed stronger growth inhibition than
      ad-p27wt. Both types of ad-p27 induced G(1)-S arrest and apoptosis; however, ad
      p27mt induced stronger G(1)-S arrest and apoptosis. Intratumoral injection of ad
      p27mt induced partial regression of established tumors and inhibited the growth
      of human lung cancer xenografts more strongly than ad-p27wt. From these results,
      we conclude that ad-p27mt has the potential to become a novel and powerful gene
      therapy tool.

PMID- 11507069
TI  - A novel cdk2-selective inhibitor, SU9516, induces apoptosis in colon carcinoma
      cells.
AB  - Recent studies have indicated that the development of cyclin-dependent kinase
      (cdk)2 inhibitors that deregulate E2F are a plausible pharmacological strategy
      for novel antineoplastic agents. We show here that 3-[1-(3H-Imidazol-4-yl)-meth
      (Z)-ylidene]-5-methoxy-1,3-dihydro-indol-2-one (SU9516), a novel 3-substituted
      indolinone compound, binds to and selectively inhibits the activity of cdk2. This
      inhibition results in a time-dependent decrease (4-64%) in the phosphorylation of
      the retinoblastoma protein pRb, an increase in caspase-3 activation (5-84%), and
      alterations in cell cycle resulting in either a G(0)-G(1) or a G(2)-M block. We
      also report here cell line differences in the cdk-dependent phosphorylation of
      pRb. These findings demonstrate that SU9516 is a selective cdk2 inhibitor and
      support the theory that compounds that inhibit cdk2 are viable resources in the
      development of new antineoplastic agents.

PMID- 11507070
TI  - Targeted interleukin 2 therapy enhances protective immunity induced by an
      autologous oral DNA vaccine against murine melanoma.
AB  - We demonstrate that a mouse-human chimeric anti-ganglioside GD2-interleukin (IL)
      2 fusion protein (ch14.18-IL2) substantially amplifies tumor-protective immunity
      against murine melanoma induced by an autologous oral DNA vaccine containing the
      murine ubiquitin gene fused to murine melanoma peptide epitopes gp100(25-35) and
      TRP-2(181-188). This combination therapy led to the complete rejection of a
      lethal challenge with B78D14 murine melanoma cells in six of eight mice and a
      marked suppression of s.c. tumor growth in the two remaining animals. The tumor
      protective immunity was mediated by MHC class I antigen- restricted CD8(+) T
      cells together with CD4(+) T cell help, which was required only for tumor cell
      killing in the effector phase of the immune response. A single oral vaccination
      with the DNA vaccine, which was carried by attenuated Salmonella typhimurium, was
      equally as effective as three such vaccinations applied at 2-week intervals. The
      immunological mechanisms involved in this antitumor effect were suggested by a
      decisively increased secretion of tumor necrosis factor alpha TNFTnTNa and IFN
      gamma from CD4(+) and CD8(+) T cells and a markedly up-regulated expression on
      CD8(+) T cells of high-affinity IL-2 receptor alpha chain (CD25), costimulatory
      molecule CD28, and adhesion molecule lymphocyte function-associated antigen-2
      (LFA-2/CD2). Additionally, the combination therapy induced increased expression
      of costimulatory molecules B7.1 and CD48 on murine antigen-presenting cells.
      Taken together, our results suggest that IL-2 targeted to the tumor
      microenvironment by a specific antibody-IL-2 fusion protein is a potent enhancer
      of tumor-protective immunity induced by an oral DNA vaccine that may ultimately
      enhance the chances of success in its clinical application.

PMID- 11507071
TI  - Loss of p53 function confers high-level multidrug resistance in neuroblastoma
      cell lines.
AB  - Neuroblastomas can acquire a sustained high-level drug resistance during
      chemotherapy and especially myeloablative chemoradiotherapy. p53 mutations are
      rare in primary neuroblastomas, but a loss of p53 function could play a role in
      multidrug resistance. We determined p53 function by measuring induction of p21
      and/or MDM2 proteins in response to melphalan (L-PAM) in seven L-PAM-sensitive
      and 11 L-PAM-resistant neuroblastoma cell lines. p53 was functional in
      seven/seven drug-sensitive but in only 4/11 drug-resistant cell lines (P = 0.01).
      In four of the seven cell lines lacking p53 function, mutations of p53 were
      detected by the microarray GeneChip p53 Assay and automated sequencing, whereas
      six cell lines with functional p53 had no evidence of p53 mutations. All of the
      cell lines with wild-type (wt) p53 showed a strong transactivation of the p53
      HBS/CAT reporter gene, whereas the four cell lines with mutant p53 failed to
      transactivate p53 HBS/CAT. Overexpression of MDM2 protein (relative to p53
      functional lines) was seen in two p53-nonfunctional cell lines with wt p53; one
      showed genomic amplification of MDM2. Nonfunctional and mutated p53 was detected
      in a resistant cell line, whereas a sensitive cell line derived from the same
      patient before treatment had functional and wt p53. Loss of p53 function was
      selectively achieved by transduction of human papillomavirus 16 E6 (which
      degrades p53) into two drug-sensitive neuroblastoma cell lines with intact p53,
      causing high-level drug resistance to L-PAM, carboplatin, and etoposide. These
      data obtained with neuroblastoma cell lines suggest that the high-level drug
      resistance observed in some recurrent neuroblastomas is attributable to p53
      mutations and/or a loss of p53 function acquired during chemotherapy. If
      confirmed in patient tumor samples, these data support development of p53
      independent therapies for consolidation and/or salvage of recurrent
      neuroblastomas.

PMID- 11507072
TI  - Interleukin-13 receptor-targeted cancer therapy in an immunodeficient animal
      model of human head and neck cancer.
AB  - Although interleukin-13 receptors (IL-13R) are overexpressed on several head and
      neck cancer cell lines, a majority of cell lines express only low levels of IL
      13R. We have found that the primary interleukin-13-binding protein IL-13Ralpha2
      chain plays an important role in ligand binding and internalization. We showed
      that the gene transfer of IL-13Ralpha2 chain into various solid tumor cell lines
      that express few IL-13Rs can dramatically sensitize cells to the cytotoxic effect
      of a recombinant chimeric protein composed of interleukin-13 and a mutated form
      of Pseudomonas exotoxin A, IL13-PE38QQR. Based on the expression of IL-13R, we
      have classified five head and neck cancer cell lines into two groups: (a) IL
      13Ralpha2 chain-positive cell lines (SCC-25 and KCCT873); and (b) IL-13Ralpha2
      chain-negative cell lines (A253, YCUT891, and KCCT871). By plasmid-mediated
      stable gene transfer, we demonstrate that not only IL-13Ralpha2 chain-positive
      head and neck cancer cell lines but also IL-13Ralpha2 chain-negative cell lines
      can dramatically increase sensitivity to IL-13 toxin by 520-1000-fold compared
      with mock-transfected control cells after genetic alteration to express high
      levels of the IL-13Ralpha2 chain. In animal studies, i.p. or intratumoral
      administration of IL13-PE38QQR given daily or on alternate days for 3-5 days
      showed dramatic tumor response with complete remission in intratumorally injected
      tumors in both IL-13Ralpha2 chain-positive and -negative but transfected with IL
      13Ralpha2 chain head and neck tumor implanted s.c. in nude mice. These results
      demonstrate that by using a combination approach of gene transfer and systemic or
      locoregional cytotoxin therapy, the IL-13R represents a new potent target for
      head and neck cancer therapy.

PMID- 11507073
TI  - Eradication of intraperitoneal and distant tumor by adenovirus-mediated
      interferon-beta gene therapy is attributable to induction of systemic immunity.
AB  - Malignant mesothelioma remains an incurable disease for which immune-modulatory
      therapies, such as exogenous cytokines, have shown some promise. One such
      cytokine, IFN-beta, has potent antiproliferative and immunostimulatory activity
      in vitro, but its in vivo use has been limited by toxicity. We thus conducted
      studies evaluating intracavitary delivery of a replication-deficient adenoviral
      (Ad) vector encoding for the murine IFN-beta gene (Ad.muIFN-beta) in mouse models
      of malignant mesothelioma. In contrast to multiple injections of recombinant
      protein, a single i.p. injection of Ad.muIFN-beta into animals with established
      tumors elicited remarkable antitumor activity leading to long-term survival in
      >90% of animals bearing either AB12 or AC29 i.p. mesotheliomas. A control
      adenovirus vector had minimal antitumor effect in vivo. Significant therapeutic
      effects were also seen in animals treated with large tumor burdens. Importantly,
      treatment of i.p. tumor also led to reduction of growth in tumors established at
      a distant site (flank). A number of experiments suggested that these effects were
      attributable to an acquired CD8(+) T-cell-mediated response including: (a) the
      induction of long-lasting antitumor immunity; (b) loss of efficacy of Ad.muIFN
      beta in tumor-bearing, immune-deficient (SCID, SCID/beige) mice; (c) detection of
      high levels of specific antitumor cytolytic activity from unstimulated
      splenocytes harvested from Ad.muIFN-beta-treated animals that was abolished by
      CD8(+) T-cell depletion; and (d) abrogation of antitumor effects of Ad.muIFN-beta
      in tumor-bearing CD8(+) T-cell-depleted animals. These data show that
      intracavitary IFN-beta gene therapy using an adenoviral vector provides strong
      CD8(+) T-cell-mediated antitumor effects in murine models of mesothelioma and
      suggest that this may be a promising strategy for the treatment of localized
      tumors such as mesothelioma or ovarian cancer in humans.

PMID- 11507074
TI  - Anticancer effects of thiazolidinediones are independent of peroxisome
      proliferator-activated receptor gamma and mediated by inhibition of translation
      initiation.
AB  - The thiazolidinedione (TZD) class of peroxisome proliferator-activated receptor
      (PPAR) gamma ligands, known for their ability to induce adipocyte differentiation
      and increase insulin sensitivity, also exhibits anticancer properties. Currently,
      TZDs are being tested in clinical trials for treatment of human cancers
      expressing high levels of PPARgamma because it is assumed that activation of
      PPARgamma mediates their anticancer activity. Using PPARgamma(-/-) and
      PPARgamma(+/+) mouse embryonic stem cells, we report here that inhibition of cell
      proliferation and tumor growth by TZDs is independent of PPARgamma. Our studies
      demonstrate that these compounds block G(1)-S transition by inhibiting
      translation initiation. Inhibition of translation initiation is the consequence
      of partial depletion of intracellular calcium stores and the resulting activation
      of protein kinase R that phosphorylates the alpha subunit of eukaryotic
      initiation factor 2 (eIF2), thus rendering eIF2 inactive. PPARgamma-independent
      inhibition of translation initiation most likely accounts for the anticancer
      properties of thiazolidinediones.

PMID- 11507075
TI  - Epstein-Barr virus-specific cytotoxic T lymphocyte responses in the blood and
      tumor site of Hodgkin's disease patients: implications for a T-cell-based
      therapy.
AB  - Approximately 40% of Hodgkin's disease (HD) cases carry EBV in the malignant
      Hodgkin-Reed Sternberg (H-RS) cells, with expression of viral latent membrane
      proteins (LMPs) 1 and 2. These viral proteins are targets for CTLs in healthy EBV
      carriers, and their expression in EBV-associated HD raises the possibility of
      targeting them for a CTL-based immunotherapy. Here we characterize the CTL
      response to EBV latent antigens in both the blood and tumor-infiltrating
      lymphocytes of HD patients using two approaches: (a) in vitro reactivation of
      CTLs by stimulation with the autologous EBV-transformed lymphoblastoid cell line;
      and (b) an enzyme-linked immunospot assay to quantify frequencies of CTLs
      specific for known LMP1/2 epitopes. We detected EBV-specific CTLs in blood and
      biopsy samples from both EBV-negative and EBV-positive HD patients. However, as
      in healthy EBV carriers, LMP-specific CTL precursors occurred only at low
      frequency in the blood of HD patients, and with the exception of one EBV-negative
      HD case, were undetectable in the tumor. These data give rise to two
      considerations: (a) they may explain why EBV-positive tumor cells persist in the
      presence of an existing EBV-specific immune response; and (b) they provide a
      rationale for selectively boosting/eliciting LMP-specific CTL responses as a
      therapy for EBV-positive HD.

PMID- 11507076
TI  - A subclass of HER1 ligands are prognostic markers for survival in bladder cancer
      patients.
AB  - Members of the epidermal growth factor (EGF) family have been suggested as
      prognostic markers in patients with bladder cancer. Thus far, there has been no
      consensus on their usefulness. We report an analysis of six ligands and two
      receptors of which a subset correlate to tumor stage and survival. Biopsies from
      bladder cancer tumors were obtained from 73 patients followed for a median of 28
      months. The mRNA content for six ligands [EGF, transforming growth factor alpha
      (TGF-alpha), amphiregulin (AR), betacellulin (betaCL), heparin-binding EGF-like
      growth factor (HB-EGF), epiregulin (EPI)] and two receptors [EGF receptor I Human
      EGF Receptor (HER1) and 2 (HER2)] was examined by a newly developed quantitative
      reverse transcription-PCR method. Five ligands and two receptors (HER1 and HER2)
      were present in median concentrations of (10(-21) mol/microg RNA) 0.39 (AR), 11
      (betaCL), 2.4 (EPI), 40 (HB-EGF), 1.4 (TGF-alpha), 75 (HER1), and 39,000 (HER2).
      EGF was barely detectable. A significantly higher expression of EPI (P < 0.001),
      HB-EGF (P < 0.001), and TGF-alpha (P < 0.05) were observed in T2-T4 tumors as
      compared with Ta tumors. Especially the expression of EPI mRNA correlated
      strongly to survival (P < 0.0005), but increased expression of TGF-alpha (P <
      0.005), AR, and HB-EGF (P < 0.02) was also associated with a reduced life span.
      For the first time, mRNA expression of six ligands and two receptors of the EGF
      family have been examined in bladder cancer tumors. Our data emphasize that
      members of the EGF family, especially EPI, may be potential bladder tumor
      markers.

PMID- 11507077
TI  - Tumor susceptibility of p21(Waf1/Cip1)-deficient mice.
AB  - The cell cycle regulator p21 mediates the ability of the tumor suppressor p53 to
      arrest cellular proliferation. We have examined the involvement of p21 in tumor
      suppression by following a large cohort of p21-deficient mice for an extended
      period of time. We report that p21-deficient mice develop spontaneous tumors at
      an average age of 16 months, whereas wild-type mice are tumor-free beyond 2 years
      of age. The tumors arising in p21-null mice derive from a variety of cell types
      and include hematopoietic ( approximately 65% of the tumors), endothelial (
      approximately 20%), and epithelial ( approximately 10%) tumors. We have also
      studied radiation-induced carcinogenesis to test whether, in this setting, p53
      exerts its tumor suppressor activity mainly through apoptosis, rather than
      through p21-mediated cell-cycle arrest. Concurring with this, p21-deficient mice
      did not show increased susceptibility to radiation-induced carcinogenesis. On the
      contrary, they were protected relative to wild-type mice. We conclude that p21,
      by mediating p53-dependent cell-cycle arrest, plays a significant role in tumor
      suppression.

PMID- 11507078
TI  - Reversion of transcriptional repression of Sp1 by 5 aza-2' deoxycytidine restores
      TGF-beta type II receptor expression in the pancreatic cancer cell line MIA PaCa
      2.
AB  - The pancreatic cancer cell line, MIA PaCa-2 is not responsive to transforming
      growth factor beta (TGF-beta) because of a lack of expression of the TGF-beta
      type II receptor (RII). We show that the lack of RII expression is caused by a
      deficit of the transcription factor Sp1. Nuclear run-off assays and Western
      immunoblot showed low levels of transcription and protein levels of Sp1,
      respectively. Treatment of MIA PaCa-2 cells with the DNA methyl transferase
      inhibitor, 5-aza-2'-deoxycytidine, resulted in an increase in the rate of Sp1
      transcription, in Sp1 protein expression, and in the binding of Sp1 to the RII
      promoter. Ectopic expression of Sp1 cDNA in MIA PaCa-2 cells led to an increase
      in RII promoter-chloramphenicol acetyltransferase activity and RII expression.
      Expression of Sp1 cDNA also caused a reduction in both growth and clonogenicity
      that was associated with restoration of responsiveness to TGF-beta. Conversely,
      cells that express RII (BxPC-3 and MIA PaCa-2 Sp1 transfectants) when treated
      with mithramycin, an inhibitor of Sp1 binding, showed a reduction in RII mRNA
      expression. The reduction of RII mRNA was attributed to a decrease in RII
      promoter-chloramphenicol acetyltransferase activity that was associated with a
      decrease in Sp1 binding to the RII promoter. These data indicate that
      transcriptional repression of the Sp1 gene in MIA PaCa-2 cells plays a role in
      the transcriptional inactivation of the RII gene and thus lack of responsiveness
      to TGF-beta.

PMID- 11507079
TI  - Expression of angiopoietin-2 in human glioma cells and its role for angiogenesis.
AB  - In highly vascular malignant glioma, glioma cells themselves may express
      angiogenic factors and induce angiogenesis. Recent studies have shown that novel
      angiogenic factors, angiopoietin-1 (Ang1) and -2 (Ang2), play important roles in
      the modulation of vasculogenesis and angiogenesis. In this study, we determined
      Ang2 mRNA expression in cultured human malignant glioma cells (U105, U251, and
      U373 MG) by reverse transcriptase-PCR. Western blot analysis and
      immunocytochemical analysis with antihuman Ang2 antibody revealed that Ang2
      protein was expressed and secreted by these cells. Furthermore, hypoxia increased
      the Ang2 protein level in cultured glioma cells. Serial sections of 32 human
      glioma tissues (14 glioblastomas, eight anaplastic astrocytomas, seven
      astrocytomas, and three pilocytic astrocytomas) were immunostained against Ang2,
      vascular endothelial growth factor, Tie2, von Willebrand factor, and alpha smooth
      muscle actin. The immunoreactivity of each angiogenic factor was higher in
      malignant gliomas than in low-grade gliomas. Ang2 protein was detected not only
      in endothelial cells but also in glioma cells, and its expression was prominent
      in both the area surrounding the necrosis and the periphery of glioblastomas. In
      the area surrounding necrosis, Ang2 was highly expressed and tumor vessels showed
      regression. In the tumor periphery, Ang2 was highly expressed and many small
      vessels stained positively for von Willebrand factor but not for alpha smooth
      muscle actin, suggesting angiogenesis. Statistical analysis revealed that the
      Ang2 expression was negatively correlated with vessel maturation in malignant
      gliomas and that vascular endothelial growth factor expression was positively
      correlated with vessel maturation in low-grade gliomas (P < 0.05). These results
      suggest that glioma cells themselves express Ang2 and that expression may be
      induced by hypoxic stimulation and may play a crucial role in the vessel
      maturation, angiogenesis, and vessel regression in malignant glioma.

PMID- 11507080
TI  - Induction of transplantable mouse renal cell cancers by streptozotocin: in vivo
      growth, metastases, and angiogenic phenotype.
AB  - Interleukin-2-based regimens of biological therapy have shown some clinical
      promise for the treatment of kidney cancer in humans, although the mechanisms
      responsible for tumor regression occurring in these patients remain unclear.
      Preclinical insight into these mechanisms is limited by a paucity of orthotopic
      animal models of kidney cancer. We have used streptozotocin, an antibiotic and
      diabetogenic nitrosamine compound derived from Streptomyces achromogenes to
      induce new kidney tumors in BALB/c mice. Single or multiple doses of
      streptozotocin induced kidney tumors in up to 25% of mice by 50-90 weeks of age,
      with up to 18% characterized as renal cell carcinomas (RCCs). Several
      transplantable lines were obtained from the RCCs, and one of these lines was
      subsequently cloned. The initial tumor isolates and sublines were histologically
      reconfirmed to be RCCs, and all grew progressively but slowly (mean survival
      times, 57 to >100 days) in vivo after intrarenal implant. None of the primary
      isolates or sublines revealed mutations in either the VHL or Ras genes, although
      karyotype analysis and chromosome painting revealed the consistent presence of a
      submetacentric chromosome resulting from the fusion of chromosomes 16 and 19.
      Biological characterization of these tumors revealed several features analogous
      to the growth of human kidney cancers, including a propensity for the formation
      of lung metastases and high vascularity. This hypervascularity is evident by both
      gross and microscopic analysis and correlates with the expression of several
      proangiogenic genes. Overall, the features of orthotopic transplantability,
      slower in vivo growth (relative to the rapid growth rates of other transplantable
      mouse kidney tumors), propensity for lung metastases, and hypervascularity may
      make these tumors valuable models for the study of new therapeutic strategies
      based on antineovascular agents and antitumor cytokines.

PMID- 11507081
TI  - Membrane type I-matrix metalloproteinase-mediated degradation of type I collagen
      by oral squamous cell carcinoma cells.
AB  - Oral squamous cell carcinomas are highly invasive lesions that destroy adjacent
      tissues and invade bone and muscle, which is most likely the result of matrix
      metalloproteinase (MMP) activity. We examined three cell lines derived from
      squamous cell carcinoma of the tongue for their intrinsic capacities to degrade
      interstitial collagen with the goal of identifying the matrix-degrading enzymes.
      SCC-25 and SCC-15 cells degrade reconstituted fibrillar type I collagen in the
      absence of exogenous growth factors or cytokines when seeded as a colony on dried
      films. Degradation is confined to the subjacent matrix, is enhanced 2-3-fold by
      phorbol ester, and is strictly MMP-dependent, as it is blocked by BB-94 and
      tissue inhibitor of metalloproteinases-2 but not by inhibitors of serine and
      cysteine proteinases. Both cell lines express active (M(r) 57,000) membrane type
      I-MMP (MT1-MMP) on their surfaces, as detected by surface biotinylation and
      immunoprecipitation. Concomitantly, both cell lines activate endogenous MMP-2
      when cultured on type I collagen films, as assessed by zymography. Phorbol ester
      treatment enhances collagen-induced MMP-2 activation, which is accompanied by the
      appearance of a surface-labeled M(r) 43,000 form of MT1-MMP. Treatment of cells
      with a synthetic furin inhibitor, which inhibits processing of the MT1-MMP
      zymogen, blocks collagen degradation. In contrast, CAL 27 cells do not degrade
      collagen under either basal or phorbol 12-myristate 13-acetate-stimulated
      conditions. Although proMT1-MMP (M(r) 63,000/65,000) is detectable in these cells
      by immunoblot analysis, they express greatly reduced levels of active MT1-MMP on
      their surfaces relative to SCC-25 and SCC-15 cells. Correspondingly, CAL 27 cells
      cultured on collagen express neither latent nor active gelatinases. Immunoblots
      of lysates and conditioned media revealed the constitutive expression of proMMP-1
      and proMMP-13 in all three cell lines. We conclude that in the absence of
      exogenous growth factors or accessory stromal cells, degradation of interstitial
      collagen by oral squamous cell carcinoma cells requires a threshold level of
      active MT1-MMP on cell surfaces.

PMID- 11507082
TI  - In vivo progression of LAPC-9 and LNCaP prostate cancer models to androgen
      independence is associated with increased expression of insulin-like growth
      factor I (IGF-I) and IGF-I receptor (IGF-IR).
AB  - Androgen deprivation therapies for metastatic prostate cancer are useful
      initially, but progression to androgen independence usually results in relapse
      within 2 years. The molecular mechanisms underlying the clinically important
      transition from androgen dependence to androgen independence are poorly
      described. Several lines of investigation have suggested that insulin-like growth
      factors (IGFs) are involved in the biology of prostate cancer, but little is
      known about their relevance to progression to androgen independence. We used
      three in vivo models of androgen-dependent (AD) human prostate cancer to study
      this issue. Progression to androgen-independent (AI) growth was associated with a
      60-fold increase in expression of IGF-I mRNA in LAPC-9 xenografts and a 28-fold
      increase in IGF-I expression in LNCAP xenografts, relative to the initial AD
      neoplasms. IGF type I receptor (IGF-IR) mRNA levels were approximately 2.5-fold
      and approximately 5-fold higher, respectively, in AI LAPC-9 and LNCaP tumors
      compared with the original AD neoplasms. AI growth of these xenografts was also
      associated with significant reductions in IGF binding protein-3 expression. LAPC
      4 xenografts, which previously have been shown to exhibit molecular pathology
      related to HER-2/neu expression with progression to AI, showed relatively minor
      changes in expression of the genes investigated, but we nevertheless found
      evidence of increased IGF-IR phosphorylation with progression to androgen
      independence in this model. Taken together with prior observations, our results
      suggest that deregulation of expression of genes related to any one of several
      critical receptor tyrosine kinase regulatory systems, including IGF signaling,
      may confer androgen independence.

PMID- 11507083
TI  - Implication of tyrosine kinase receptor and steel factor in cell density
      dependent growth in cervical cancers and leukemias.
AB  - Cell-cell interaction is important in the expansion of leukemic cells and of
      solid tumors. Steel factor (SF) or Kit ligand is produced as a membrane-bound
      form (mSF) and a soluble form. Because both primary gynecological tumors and
      primary leukemic cells from patients with acute myeloblastic leukemia (AML) have
      been shown to coexpress c-Kit and SF, we addressed the question of whether mSF
      could contribute to cell interaction in these cancers. Investigations on primary
      cervical carcinomas have been hindered by the fact that the cells do not grow in
      culture. We report herein the establishment of two cervical carcinoma cell lines,
      CALO and INBL, that reproduce the pattern of SF/c-Kit expression observed in
      primary tumor samples. In addition, these cells exhibit marked density-dependent
      growth much in the same way as AML blasts. Using an antisense strategy with
      phosphorothioate-modified oligonucleotides that specifically target SF without
      affecting other surface markers, we provide direct evidence for a role of mSF and
      c-Kit in cell interaction and cell survival in these gynecological tumor cell
      lines as well as in primary AML blasts. Finally, our study defines the importance
      of juxtacrine stimulation, which may be as important, if not more, than autocrine
      stimulation in cancers.

PMID- 11507084
TI  - An IkappaBalpha inhibitor causes leukemia cell death through a p38 MAP kinase
      dependent, NF-kappaB-independent mechanism.
AB  - Treatment of U937 cells with an IkappaBalpha phosphorylation inhibitor, Bay 11
      7085, induced a rapid phosphorylation of p38 mitogen-activated protein (MAP)
      kinase, significant apoptosis, extensive necrosis, and a weak phosphorylation of
      MAP kinase kinase. Bay 11-7085 had no effect on the basal levels of
      phosphorylated IkappaBalpha but completely inhibited phorbol 12-myristate 13
      acetate-induced phosphorylation of IkappaBalpha. Although Bay 11-7085 prevented
      phorbol 12-myristate 13-acetate-induced NF-kappaB nuclear translocation, SN50, a
      specific inhibitor of nuclear translocation and function of NF-kappaB, did not
      induce any significant nuclear/DNA fragmentation, caspase 3 activation, or cell
      death. The p38 MAP kinase-specific inhibitor, SB203580, completely inhibited the
      phosphorylation of p38 MAP kinase and significantly decreased Bay 11-7085-induced
      apoptosis. In contrast, the MAP kinase kinase-specific inhibitor PD98059 had no
      effect on Bay 11-7085-induced apoptosis. Caspase-specific inhibitor, z-Val-Ala
      Asp-fluoromethyl ketone prevented Bay 11-7085-induced activation of caspase 3 but
      was not able to block Bay 11-7085-induced phosphorylation of p38 MAP kinase.
      These data suggest that Bay 11-7085 induces apoptosis through a p38 MAP kinase
      dependent, NF-kappaB-independent mechanism.

PMID- 11507085
TI  - p21(WAF1/cip1) is an important determinant of intestinal cell response to
      sulindac in vitro and in vivo.
AB  - Sulindac, a nonsteroidal anti-inflammatory drug, inhibits intestinal
      tumorigenesis in humans and rodents. Sulindac induced complex alterations in gene
      expression, but only 0.1% of 8063 sequences assayed were altered similarly by the
      drug in rectal biopsies of patients treated for 1 month and during response of
      colonic cells in culture. Among these changes was induction of the cyclin
      dependent kinase inhibitor, p21(WAF1/cip1). In Apc1638(+/-) mice, targeted
      inactivation of p21 increased intestinal tumor formation in a gene-dose-dependent
      manner, but inactivation of p21 completely eliminated the ability of sulindac to
      both inhibit mitotic activity in the duodenal mucosa and to inhibit Apc-initiated
      tumor formation. Thus, p21 is essential for tumor inhibition by this drug. The
      array data can be accessed on the Internet at
      http://sequence.aecom.yu.edu/genome/.

PMID- 11507087
TI  - Beta(2)-adrenergic receptor agonists increase intracellular free Ca(2+)
      concentration cycling in ventricular cardiomyocytes through p38 and p42/44 MAPK
      mediated cytosolic phospholipase A(2) activation.
AB  - We have recently reported that arachidonic acid mediates beta(2)-adrenergic
      receptor (AR) stimulation of [Ca(2+)](i) cycling and cell contraction in
      embryonic chick ventricular cardiomyocytes (Pavoine, C., Magne, S., Sauvadet, A.,
      and Pecker, F. (1999) J. Biol. Chem. 274, 628-637). In the present work, we
      demonstrate that beta(2)-AR agonists trigger arachidonic acid release via
      translocation and activation of cytosolic phospholipase A(2) (cPLA(2)) and
      increase caffeine-releasable Ca(2+) pools from Fura-2-loaded cells. We also show
      that beta(2)-AR agonists trigger a rapid and dose-dependent phosphorylation of
      both p38 and p42/44 MAPKs. Translocation and activation of cPLA(2), as well as
      Ca(2+) accumulation in sarcoplasmic reticulum stores sensitive to caffeine and
      amplification of [Ca(2+)](i) cycling in response to beta(2)-AR agonists, were
      blocked by inhibitors of the p38 or p42/44 MAPK pathway (SB203580 and PD98059,
      respectively), suggesting a role of both MAPK subtypes in beta(2)-AR stimulation.
      In contrast, beta(1)-AR stimulation of [Ca(2+)](i) cycling was rather limited by
      the MAPKs, clearly proving the divergence between beta(2)-AR and beta(1)-AR
      signaling systems. This study presents the first evidence for the coupling of
      beta(2)-AR to cardiac cPLA(2) and points out the key role of the MAPK pathway in
      the intracellular signaling elicited by positive inotropic beta(2)-AR agonists in
      heart.

PMID- 11507088
TI  - Inhibition of MDM2 by hsp90 contributes to mutant p53 stabilization.
AB  - Stabilization and overexpression are hallmarks of mutant p53 found in nearly 50%
      of human tumors. Mutations in the conformation-sensitive core domain of p53 often
      lead to association with molecular chaperones such as hsp70 and hsp90. Inhibition
      of hsp90 function accelerates mutant p53 degradation. We recently found that
      expression of p53 core domain mutants inhibits MDM2 degradation, suggesting that
      mutant p53 can modulate MDM2 functions. In this report, we show that mutant p53
      mediates formation of MDM2-p53-hsp90 complexes. Release of MDM2 from the p53
      hsp90 complex after DNA damage restores MDM2 but not p53 turnover, whereas
      dissociation of hsp90 by geldanamycin increases the degradation of both MDM2 and
      mutant p53. Mutant p53 degradation after hsp90 inhibition requires MDM2
      expression. The interaction between MDM2 and hsp90 is disrupted by the 2A10
      antibody, which recognizes a site on MDM2 important for binding to alternative
      reading frame (ARF). Expression of mutant p53 prevents MDM2 from binding ARF and
      accumulating in the nucleolus in an hsp90-dependent fashion. These results
      suggest that hsp90 recruited by mutant p53 conceals the ARF-binding site on MDM2
      and inhibits its ubiquitin-protein isopeptide ligase function, resulting in the
      stabilization of both mutant p53 and MDM2.

PMID- 11507089
TI  - Four tyrosine residues in phospholipase C-gamma 2, identified as Btk-dependent
      phosphorylation sites, are required for B cell antigen receptor-coupled calcium
      signaling.
AB  - Activation of phospholipase C-gamma2 (PLCgamma2) is the critical step in B cell
      antigen receptor (BCR)-coupled calcium signaling. Although genetic dissection
      experiments on B cells have demonstrated that Bruton's tyrosine kinase (Btk) and
      Syk are required for activating PLCgamma2, the exact activation mechanism of
      PLCgamma2 by these kinases has not been established. We identify the tyrosine
      residues 753, 759, 1197, and 1217 in rat PLCgamma2 as Btk-dependent
      phosphorylation sites by using an in vitro kinase assay. To evaluate the role of
      these tyrosine residues in phosphorylation-dependent activation of PLCgamma2,
      PLCgamma2-deficient DT40 cells were reconstituted with a series of mutant
      PLCgamma2s in which the phenylalanine was substituted for tyrosine. Substitution
      of all four tyrosine residues almost completely eliminated the BCR-induced
      PLCgamma2 phosphorylation, indicating that these residues include the major
      phosphorylation sites upon BCR engagement. Cells expressing PLCgamma2 with a
      single substitution exhibited some extent of reduction in calcium mobilization,
      whereas those expressing quadruple mutant PLCgamma2 showed greatly reduced
      calcium response. These findings indicate that the phosphorylations of the
      tyrosine residues 753, 759, 1197, and 1217, which have been identified as Btk
      dependent phosphorylation sites in vitro, coordinately contribute to BCR-induced
      activation of PLCgamma2.

PMID- 11507090
TI  - UV Induces phosphorylation of protein kinase B (Akt) at Ser-473 and Thr-308 in
      mouse epidermal Cl 41 cells through hydrogen peroxide.
AB  - The exposure of mammalian cells to UV irradiation leads to the activation of
      transcription factors and protein kinases, which are believed to be responsible
      for the carcinogenic effects of excessive sun exposure. The present study
      investigated the effect of UV exposure on reactive oxygen species (ROS)
      generation and protein kinase B (Akt) phosphorylation in epidermal cells and
      determined if a relationship exists between these UV responses. Exposure of mouse
      epidermal JB6 Cl 41 cells to UV radiation led to specific phosphorylation of Akt
      at Ser-473 and Thr-308 in a time-dependent manner. This phosphorylation was
      confirmed by the observation that overexpression of Akt mutant, Akt-T308/S473A,
      attenuated phosphorylation of Akt at Ser-473 and Thr-308. UV radiation also
      generated ROS as measured by electron spin resonance (ESR) in JB6 Cl 41 cells.
      The generation of ROS by UV radiation was measured further by H(2)O(2) and O(-.2)
      fluorescence staining assays. The mechanism of ROS generation involved reduction
      of molecular oxygen to O(-.2), which generated H(2)O(2) through dismutation.
      H(2)O(2) produced .OH via a metal-independent pathway. The scavenging of UV
      generated H(2)O(2) by N-acety-l-cyteine (NAC, a general antioxidant) or catalase
      (a specific H(2)O(2) inhibitor) inhibited Akt phosphorylation at Ser-473 and Thr
      308, whereas the pretreatment of cells with sodium formate (an .OH radical
      scavenger) or superoxide dismutase (an O(-.2) radical scavenger) did not show any
      inhibitory effects. Furthermore, treatment of cells with H(2)O(2) increased UV
      induced phosphorylation of Akt at Ser-473 and Thr-308. These results demonstrate
      that UV radiation generates a whole spectrum of ROS including O(-.2), .OH, and
      H(2)O(2) and induces phosphorylation of Akt at Ser-473. Among the various ROS,
      H(2)O(2) seems most potent in mediating UV-induced phosphorylation of Akt at Ser
      473 and Thr-308. It is possible that Akt may play a role in the carcinogenesis
      effects by UV radiation.

PMID- 11507091
TI  - Recognition of alpha 2-macroglobulin by the low density lipoprotein receptor
      related protein requires the cooperation of two ligand binding cluster regions.
AB  - The low density lipoprotein receptor-related protein (LRP) is a scavenger
      receptor that binds several ligands including the activated form of the pan
      proteinase inhibitor alpha(2)-macroglobulin (alpha(2)M*) and amyloid precursor
      protein, two ligands genetically linked to Alzheimer's disease. To delineate the
      contribution of LRP to this disease, it will be necessary to identify the sites
      on this receptor which are responsible for recognizing these and other ligands to
      assist in the development of specific inhibitors. Structurally, LRP contains four
      clusters of cysteine-rich repeats, yet studies thus far suggest that only two of
      these clusters (clusters II and IV) bind ligands. Identifying binding sites
      within LRP for certain ligands, such as alpha(2)M*, has proven to be difficult.
      To accomplish this, we mapped the binding site on LRP for two inhibitors of
      alpha(2)M* uptake, monoclonal antibody 8G1 and an amino-terminal fragment of
      receptor-associated protein (RAP D1D2). Surprisingly, the inhibitors recognized
      different clusters of ligand binding repeats: 8G1 bound to repeats within cluster
      I, whereas the RAP fragment bound to repeats within cluster II. A recombinant LRP
      mini-receptor containing the repeats from cluster I along with three ligand
      binding repeats from cluster II was effective in mediating the internalization of
      (125)I-labeled alpha(2)M*. Together, these studies indicate that ligand binding
      repeats from both cluster I and II cooperate to generate a high affinity binding
      site for alpha(2)M*, and they suggest a strategy for developing specific
      inhibitors to block alpha(2)M* binding to LRP by identifying molecules capable of
      binding repeats in cluster I.

PMID- 11507092
TI  - Immotile sperm and infertility in mice lacking mitochondrial voltage-dependent
      anion channel type 3.
AB  - Voltage-dependent anion channels (VDACs), also known as mitochondrial porins, are
      small channel proteins involved in the translocation of metabolites across the
      mitochondrial outer membrane. A single channel-forming protein is found in yeast,
      whereas higher eukaryotes express multiple VDACs, with humans and mice each
      harboring three distinct channels (VDAC1-3) encoded by separate genes. To begin
      to assess the functions of each of the three isoforms, the VDAC3 gene was
      inactivated by targeted disruption in embryonic stem cells. Here we show that
      mice lacking VDAC3 are healthy, but males are infertile. Although there are
      normal sperm numbers, the sperm exhibit markedly reduced motility. Structural
      defects were found in two-thirds of epididymal axonemes, with the most common
      abnormality being loss of a single microtubule doublet at a conserved position
      within the axoneme. In testicular sperm, the defect was only rarely observed,
      suggesting that instability of a normally formed axoneme occurs with sperm
      maturation. In contrast, tracheal epithelial cilia showed no structural
      abnormalities. In addition, skeletal muscle mitochondria were abnormally shaped,
      and activities of the respiratory chain complexes were reduced. These results
      demonstrate that axonemal defects may be caused by associated nonaxonemal
      components such as mitochondrial channels and illustrate that normal
      mitochondrial function is required for stability of the axoneme.

PMID- 11507093
TI  - Purification and characterization of membrane-associated CooC protein and its
      functional role in the insertion of nickel into carbon monoxide dehydrogenase
      from Rhodospirillum rubrum.
AB  - The accessory protein CooC, which contains a nucleotide-binding domain (P-loop)
      near the N terminus, participates in the maturation of the nickel center of
      carbon monoxide dehydrogenase (CODH). In this study, CooC was purified from the
      chromatophore membranes of Rhodospirillum rubrum with a 3,464-fold purification
      and a 0.8% recovery, and its biochemical properties were characterized. CooC is a
      homodimer with a molecular mass of 61-63 kDa, contains less than 0.1 atom of
      Ni(2+) or Fe(2+) per dimer, and has a lambda(max) at 277.5 nm (epsilon(277.5)
      32.1 mm(-1) cm(-1)) with no absorption peaks at the visible region. CooC
      catalyzes the hydrolysis of ATP and GTP with K(m) values of 24.4 and 26.0 microm
      and V(max) values of 58.7 and 3.7 nmol/min/mg protein for ATP and GTP hydrolysis,
      respectively. The P-loop mutated form of K13Q CooC was generated by site-specific
      replacement of lysine by glutamine and was purified according to the protocol for
      wild-type CooC purification. The K13Q CooC was inactive both in ATP hydrolysis
      and in vivo nickel insertion. In vitro nickel activation of apoCODH in the cell
      extracts from UR2 (wild type) and UR871 (K13Q CooC) showed that activation of
      nickel-deficient CODH was enhanced by CooC and dependent upon ATP hydrolysis. The
      overall results suggest that CooC couples ATP hydrolysis with nickel insertion
      into apoCODH. On the basis of our results and models for analogous systems, the
      functional roles of CooC in nickel processing into the active site of CODH are
      presented.

PMID- 11507094
TI  - CD98-mediated links between amino acid transport and beta 1 integrin distribution
      in polarized columnar epithelia.
AB  - In non-polarized cells, CD98 has been shown to both influence beta(1) integrins
      and heterodimerize with LAT-2, which confers amino acid transport capability on
      the LAT-2/CD98 heterodimer. Since LAT-2 is most heavily expressed in intestine
      and CD98 associates with the beta(1) integrin splice form selectively found in
      such epithelia, we investigated the relationship and polarity of these proteins
      using the intestinal epithelial model Caco2-BBE. CD98 was found to selectively
      coimmunoprecipitate with both LAT-2 and beta(1) integrin, and, logically, all
      three proteins were polarized to the same (basolateral) domain. Furthermore,
      expression of CD98 in polarized epithelia lacking human CD98 (MDCK cells)
      disrupted beta(1) integrin surface distribution and cytoskeletal architecture,
      suggesting that CD98 can influence integrin function. Expression of a CD98 mutant
      lacking the specific residues conferring LAT-2 binding similarly affected cells,
      confirming that the latter effect was not due to LAT-2 sequestration. Use of CD98
      truncation mutants suggest that a 10-amino acid domain located at the putative
      cytoplasmic tail/transmembrane domain interface was necessary and sufficient to
      induce the phenotype change. We conclude that the CD98/LAT-2 amino acid
      transporter is polarized to the same domain on which beta(1) integrin resides.
      CD98 appears to associate with beta(1) integrin and, in doing so, may influence
      its function as revealed by disruption of the outside-in signaling that confers
      cytoskeletal organization. Furthermore, such findings suggest a link between
      classic transport events and a critical element of barrier function: integrin
      mediated influences on cytoskeletal organization.

PMID- 11507095
TI  - The angiotensin II AT2 receptor is an AT1 receptor antagonist.
AB  - The vasopressor angiotensin II activates AT(1) and AT(2) receptors. Most of the
      known in vivo effects of angiotensin II are mediated by AT(1) receptors while the
      biological functions of AT(2) receptors are less clear. We report here that the
      AT(2) receptor binds directly to the AT(1) receptor and thereby antagonizes the
      function of the AT(1) receptor. The AT(1)-specific antagonism of the AT(2)
      receptor was independent of AT(2) receptor activation and signaling, and it was
      effective on different cells and on human myometrial biopsies with AT(1)/AT(2)
      receptor expression. Thus, the AT(2) receptor is the first identified example of
      a G-protein-coupled receptor which acts as a receptor-specific antagonist.

PMID- 11507096
TI  - The bile acid glycochenodeoxycholate induces trail-receptor 2/DR5 expression and
      apoptosis.
AB  - Toxic bile salts induce hepatocyte apoptosis by both Fas-dependent and 
      independent mechanisms. In this study, we examined the cellular mechanisms
      responsible for Fas-independent, bile acid-mediated apoptosis. HuH-7 cells, which
      are known to be Fas deficient, were stably transfected with the sodium-dependent
      bile acid transporting polypeptide. The toxic bile acid glycochenodeoxycholate
      (GCDC)-induced apoptosis in these cells in a time- and concentration-dependent
      manner. Apoptosis and mitochondrial cytochrome c release were inhibited by
      transfection with dominant negative FADD, CrmA transfection, or treatment with
      the selective caspase 8 inhibitor IETD-CHO. These observations suggested the Fas
      independent apoptosis was also death receptor mediated. Reverse transcriptase
      polymerase chain reaction demonstrated tumor necrosis factor-R1, tumor necrosis
      factor-related apoptosis inducing ligand (TRAIL)-R1/DR4, -R2/DR5, and TRAIL, but
      not tumor necrosis factor-alpha expression by these cells. GCDC treatment
      increased expression of TRAIL-R2/DR5 mRNA and protein 10-fold while expression of
      TRAIL-R1 was unchanged. Furthermore, aggregation of TRAIL-R2/DR5, but not TRAIL
      R1/DR4 was observed following GCDC treatment of the cells. Induction of TRAIL
      R2/DR5 expression and apoptosis by bile acids provides new insights into the
      mechanisms of hepatocyte apoptosis and the regulation of TRAIL-R2/DR5 expression.

PMID- 11507097
TI  - Subcellular distribution of superoxide dismutases (SOD) in rat liver: Cu,Zn-SOD
      in mitochondria.
AB  - Rat liver was homogenized in isotonic buffer, fractionated by differential
      centrifugation, and then subfractionated by equilibrium sedimentation in Nycodenz
      gradients. Fractions were assayed for both Cu,Zn-superoxide dismutase (SOD) and
      Mn-SOD by exploiting the cyanide sensitivity of the former activity and by the
      use of specific antibodies. As expected, the cytosol and lysosomal fractions
      contained Cu,Zn-SOD; while the mitochondrial matrix contained Mn-SOD. In
      mitochondria, Cu,Zn-SOD was found in the intermembrane space and Mn-SOD in the
      matrix and also on the inner membrane. The Mn-SOD associated with the inner
      membrane was solubilized by 0.5 m NaCl. Surprisingly the intracellular membrane
      fraction (microsomes) contained bound Cu,Zn-SOD that could be solubilized with a
      detergent, and to lesser degree with 0.5 m NaCl. Both the cytosolic and
      mitochondrial Cu,Zn-SODs were isolated and compared. They have identical
      molecular mass, cyanide sensitivity, SDS sensitivity, heat stability, and
      chloroform + ethanol stability. Tissue from Cu,Zn-SOD knockout mice was entirely
      devoid of Cu,Zn-SOD; indicating that the cytosolic and the intermembrane space
      Cu,Zn-SODs are coded for by the same gene. The significance of this distribution
      of the SODs is discussed.

PMID- 11507098
TI  - Activation of protein kinase D by signaling through Rho and the alpha subunit of
      the heterotrimeric G protein G13.
AB  - Protein kinase D (PKD/PKCmu) immunoprecipitated from COS-7 cells transiently
      transfected with either a constitutively active mutant of Rho (RhoQ63L) or the
      Rho-specific guanine nucleotide exchange factor pOnco-Lbc (Lbc) exhibited a
      marked increase in basal activity. Addition of aluminum fluoride to cells co
      transfected with PKD and wild type Galpha(13) also induced PKD activation. Co
      transfection of Clostridium botulinum C3 toxin blocked activation of PKD by
      RhoQ63L, Lbc, or aluminum fluoride-stimulated Galpha(13). Treatment with the
      protein kinase C inhibitors GF I or Ro 31-8220 prevented the increase in PKD
      activity induced by RhoQ63L, Lbc, or aluminum fluoride-stimulated Galpha(13). PKD
      activation in response to Galpha(13) signaling was also completely prevented by
      mutation of Ser-744 and Ser-748 to Ala in the kinase activation loop of PKD. Co
      expression of C. botulinum C3 toxin and a COOH-terminal fragment of Galpha(q)
      that acts in a dominant-negative fashion blocked PKD activation in response to
      agonist stimulation of bombesin receptor. Expression of the COOH-terminal region
      of Galpha(13) also attenuated PKD activation in response to bombesin receptor
      stimulation. Our results show that Galpha(13) contributes to PKD activation
      through a Rho- and protein kinase C-dependent signaling pathway and indicate that
      PKD activation is mediated by both Galpha(q) and Galpha(13) in response to
      bombesin receptor stimulation.

PMID- 11507099
TI  - Probing conformational changes in the I-like domain and the cysteine-rich repeat
      of human beta 3 integrins following disulfide bond disruption by cysteine
      mutations: identification of cysteine 598 involved in alphaIIbbeta3 activation.
AB  - We have investigated receptor function and epitope expression of recombinant
      alpha(IIb)beta(3) mutated at Cys(177) or Cys(273) in the I-like domain as well as
      Cys(598), located in the fourth repeat of the membrane-proximal cysteine-rich
      region and mutated in a Glanzmann's thrombasthenia type II patient. The beta(3)
      mutants beta(3)C177A, beta(3)C273A, and beta(3)C598Y exhibited a decreased
      electrophoretic mobility in SDS-polyacrylamide gel electrophoresis under
      nonreducing conditions, confirming the disruption of the respective disulfide
      loops. Despite reduced surface expression, the alpha(IIb)beta(3)C177A,
      alpha(IIb)beta(3)C273A, and alpha(IIb)beta(3)C598Y receptors mediated cell
      adhesion to immobilized fibrinogen and translocated into focal adhesion plaques.
      The beta(3)C598Y mutation, but not the beta(3)C177A or beta(3)C273A mutations,
      induced spontaneous binding of the ligand mimetic monoclonal antibody PAC-1,
      while the beta(3)C177A and beta(3)C273A mutants exhibited reduced complex
      stability in the absence of Ca(2+). Epitope mapping of function-blocking
      monoclonal antibodies (mAbs) allowed the identification of two distinct
      subgroups; mAbs A2A9, pl2-46, 10E5, and P256 did not interact with
      alpha(IIb)beta(3)C273A and bound only weakly to alpha(IIb)beta(3)C177A, while
      mAbs AP2, LM609 and 7E3 bound normally to mutant alpha(IIb)beta(3)C273A, but
      interacted only weakly with mutant alpha(IIb)beta(3)C177A. Furthermore, a cryptic
      epitope recognized by mAb 4D10G3 and not exposed on wild type alpha(IIb)beta(3)
      became accessible only on mutant alpha(IIb)beta(3)C177A and was mapped to the 60
      kDa chymotrypsin fragment of beta(3). Finally, the ligand-induced binding site
      (LIBS) epitopes AP5, D3, LIBS1, and LIBS2 were spontaneously expressed on all
      three mutants independent of RGDS or dithiothreitol treatment. Our results
      provide evidence that disruption of a single cysteine disulfide bond in the
      cysteine-rich repeat domain, but not in the I-like domain, activates integrin
      alpha(IIb)beta(3). In contrast, disruption of each of the disulfide bonds in the
      two long insertions of the I-like domain predicted to be in close contact with
      the alpha subunit beta-propeller domain affect the stability of the
      alpha(IIb)beta(3) heterodimer and inhibit complex-specific mAb binding without
      affecting the RGD binding capacity of the metal ion-dependent adhesion site-like
      domain.

PMID- 11507100
TI  - Ryanodine sensitizes the Ca(2+) release channel (ryanodine receptor) to Ca(2+)
      activation.
AB  - Ryanodine, a plant alkaloid, is one of the most widely used pharmacological
      probes for intracellular Ca(2+) signaling in a variety of muscle and non-muscle
      cells. Upon binding to the Ca(2+) release channel (ryanodine receptor), ryanodine
      causes two major changes in the channel: a reduction in single-channel
      conductance and a marked increase in open probability. The molecular mechanisms
      underlying these alterations are not well understood. In the present study, we
      investigated the gating behavior and Ca(2+) dependence of the wild type (wt) and
      a mutant cardiac ryanodine receptor (RyR2) after being modified by ryanodine.
      Single-channel studies revealed that the ryanodine-modified wt RyR2 channel was
      sensitive to inhibition by Mg(2+) and to activation by caffeine and ATP. In the
      presence of Mg(2+), the ryanodine-modified single wt RyR2 channel displayed a
      sigmoidal Ca(2+) dependence with an EC(50) value of 110 nm, whereas the ryanodine
      unmodified single wt channel exhibited an EC(50) of 120 microm for Ca(2+)
      activation, indicating that ryanodine is able to increase the sensitivity of the
      wt RyR2 channel to Ca(2+) activation by approximately 1,000-fold. Furthermore,
      ryanodine is able to restore Ca(2+) activation and ligand response of the E3987A
      mutant RyR2 channel that has been shown to exhibit approximately 1,000-fold
      reduction in Ca(2+) sensitivity to activation. The E3987A mutation, however,
      affects neither [(3)H]ryanodine binding to, nor the stimulatory and inhibitory
      effects of ryanodine on, the RyR2 channel. These results demonstrate that
      ryanodine does not "lock" the RyR channel into an open state as generally
      believed; rather, it sensitizes dramatically the channel to activation by Ca(2+).

PMID- 11507101
TI  - Characterization of binding of leukotriene C4 by human multidrug resistance
      protein 1: evidence of differential interactions with NH2- and COOH-proximal
      halves of the protein.
AB  - Multidrug resistance protein 1 (MRP1) is capable of actively transporting a wide
      range of conjugated and unconjugated organic anions. The protein can also
      transport additional conjugated and unconjugated compounds in a GSH- or S-methyl
      GSH-stimulated manner. How MRP1 binds and transports such structurally diverse
      substrates is not known. We have used [(3)H]leukotriene C(4) (LTC(4)), a high
      affinity glutathione-conjugated physiological substrate, to photolabel intact
      MRP1, as well as fragments of the protein expressed in insect cells. These
      studies revealed that: (i) LTC(4) labels sites in the NH(2)- and COOH-proximal
      halves of MRP1, (ii) labeling of the NH(2)-half of MRP1 is localized to a region
      encompassing membrane-spanning domain (MSD) 2 and nucleotide binding domain (NBD)
      1, (iii) labeling of this region is dependent on the presence of all or part of
      the cytoplasmic loop (CL3) linking MSD1 and MSD2, but not on the presence of
      MSD1, (iv) labeling of the NH(2)-proximal site is preferentially inhibited by S
      methyl GSH, (v) labeling of the COOH-proximal half of the protein occurs in a
      region encompassing transmembrane helices 14-17 and appears not to require NBD2
      or the cytoplasmic COOH-terminal region of the protein, (vi) labeling of intact
      MRP1 by LTC(4) is strongly attenuated in the presence of ATP and vanadate, and
      this decrease in labeling is attributable to a marked reduction in LTC(4) binding
      to the NH(2)-proximal site, and (vii) the attenuation of LTC(4) binding to the
      NH(2)-proximal site is a consequence of ATP hydrolysis and trapping of Vi-ADP
      exclusively at NBD2. These data suggest that MRP1-mediated transport involves a
      conformational change, driven by ATP hydrolysis at NBD2, that alters the affinity
      with which LTC(4) binds to one of two sites composed, at least in part, of
      elements in the NH(2)-proximal half of the protein.

PMID- 11507102
TI  - Natural osmolyte trimethylamine N-oxide corrects assembly defects of mutant
      branched-chain alpha-ketoacid decarboxylase in maple syrup urine disease.
AB  - Maple syrup urine disease is caused by deficiency in the mitochondrial branched
      chain alpha-ketoacid dehydrogenase (BCKD) complex. The clinical phenotype
      includes often fatal ketoacidosis, neurological derangement, and mental
      retardation. The type IA mutations Y393N-alpha, Y368C-alpha, and F364C-alpha,
      which occur in the E1alpha subunit of the decarboxylase (E1) component of the
      BCKD complex, impede the conversion of an alphabeta heterodimeric intermediate to
      a native alpha(2)beta(2) heterotetramer in the E1 assembly pathway. In the
      present study, we show that a natural osmolyte trimethylamine N-oxide (TMAO) at
      the optimal 1 m concentration restores E1 activity, up to 50% of the wild type,
      in the mutant E1 carrying the above missense mutations. TMAO promotes the
      conversion of otherwise trapped mutant heterodimers to active heterotetramers.
      This slow step does not involve dissociation/reassociation of the mutant
      heterodimers, which are preformed in the presence of chaperonins GroEL/GroES and
      Mg-ATP. The TMAO-stimulated mutant E1 activity is remarkably stable upon removal
      of the osmolyte, when cofactor thiamine pyrophosphate and the transacylase
      component of the BCKD complex are present. The above in vitro results offer the
      use of chemical chaperones such as TMAO as an approach to mitigate assembly
      defects caused by maple syrup urine disease mutations.

PMID- 11507103
TI  - The stomach divalent ion-sensing receptor scar is a modulator of gastric acid
      secretion.
AB  - Divalent cation receptors have recently been identified in a wide variety of
      tissues and organs, yet their exact function remains controversial. We have
      previously identified a member of this receptor family in the stomach and have
      demonstrated that it is localized to the parietal cell, the acid secretory cell
      of the gastric gland. The activation of acid secretion has been classically
      defined as being regulated by two pathways: a neuronal pathway (mediated by
      acetylcholine) and an endocrine pathway (mediated by gastrin and histamine).
      Here, we identified a novel pathway modulating gastric acid secretion through the
      stomach calcium-sensing receptor (SCAR) located on the basolateral membrane of
      gastric parietal cells. Activation of SCAR in the intact rat gastric gland by
      divalent cations (Ca(2+) or Mg(2+)) or by the potent stimulator gadolinium
      (Gd(3+)) led to an increase in the rate of acid secretion through the apical
      H+,K+ -ATPase. Gd(3+) was able to activate acid secretion through the omeprazole
      sensitive H+,K+ -ATPase even in the absence of the classical stimulator
      histamine. In contrast, inhibition of SCAR by reduction of extracellular cations
      abolished the stimulatory effect of histamine on gastric acid secretion,
      providing evidence for the regulation of the proton secretory transport protein
      by the receptor. These studies present the first example of a member of the
      divalent cation receptors modulating a plasma membrane transport protein and may
      lead to new insights into the regulation of gastric acid secretion.

PMID- 11507104
TI  - Suppression of allograft rejection in the sponge Suberites domuncula by FK506 and
      expression of genes encoding FK506-binding proteins in allografts.
AB  - Porifera (sponges) are, evolutionarily, the oldest metazoan phylum. Recent
      molecular data suggest that these animals possess molecules similar to and
      homologous with those of the innate and adaptive immune systems of higher
      Metazoa. Applying the biological system of parabiosis and the technique of
      differential display of mRNA, two cDNAs encoding putative FK506-binding proteins
      were isolated. FK506 is successfully used in clinics as a drug to prevent
      allograft rejection and is toxic to Suberites domuncula cells in vitro at doses
      above 100ng ml(-1). Autograft fusion of transplants from S. domuncula was not
      affected by FK506. Allograft non-fusion was not affected by FK506 at toxic doses;
      however, at the non-toxic dose of 20ng ml(-1), the allografts fused with each
      other. It is shown that at the attachment zone in untreated and (particularly
      drastic) in FK506-treated allografts, expression of the genes encoding the FK506
      binding proteins is upregulated. These data indicate that the drug FK506
      suppresses allograft rejection in S. domuncula, most probably via interaction
      with expression of the gene coding for the FK506-binding proteins.

PMID- 11507105
TI  - Flight-motor-driven respiratory air flow in the hawkmoth Manduca sexta.
AB  - Intratracheal pressure during tethered flight was analyzed at the anterior
      spiracles and mesoscutellar air sacs in the hawkmoth Manduca sexta using
      electronic pressure sensors. CO(2) emission from the anterior spiracles and the
      posterior thoracic and abdominal spiracles was measured using a URAS gas analyzer
      with a split-specimen chamber. Experiments were accompanied by photocell
      recordings of the wingbeat. The structural differences between the mesothoracic
      and metathoracic spiracles are described. Deformations of the lateral thorax and
      their effect upon the spiracles were observed under stroboscopic light. During
      shivering, ventilation pulses are generated by the flight muscles reminiscent of
      an autoventilation mechanism with tidal air flow. During steady flight, however,
      a unidirectional airstream arises with a mean negative (subatmospheric) pressure
      at the first (mesothoracic) spiracles and a mean positive pressure in the
      mesoscutellar air sacs. As a result of this pressure difference during flight,
      CO(2) is emitted only at the posterior spiracles. The suction force for the
      inspiration flow at the anterior spiracles is generated by the flight apparatus
      as a result of prevention of inspiration through the posterior thoracic
      spiracles. During the downstroke, the volume of the thoracic air sacs increases,
      while the posterior thoracic spiracles are automatically enclosed in the subalar
      cleft below the wing hinge and are probably closed. During the upstroke, the air
      sac volume decreases and the moth expires through the open posterior spiracles.

PMID- 11507106
TI  - Mechanical properties of red and white swimming muscles as a function of the
      position along the body of the eel Anguilla anguilla.
AB  - The way in which muscles power steady swimming depends on a number of factors,
      including fibre type and recruitment, muscle strain, stimulation pattern and
      intensity, and the intrinsic mechanical properties of the muscle fibres. For a
      number of undulatory swimming fish species, in vivo studies have shown that
      muscles at different positions along the body are stimulated during different
      phases of the strain cycle. Moreover, some intrinsic contractile properties of
      the muscles have been found to vary according to their position along the body.
      We report the first results on the mechanical properties of the red and white
      muscles of an anguilliform swimmer, Anguilla anguilla. Small preparations (0.147
      1.335 mg dry mass) were dissected from positions at fractions of 0.2, 0.4, 0.6
      and 0.8 of total body length (BL). We determined the time to 50% and 100% peak
      force and from the last stimulus to 50% relaxation for isometric contractions; we
      measured the sarcomere lengths that coincided with in situ resting length. None
      of these quantities varied significantly with the longitudinal position from
      which the fibres were taken. We also measured power and work output during
      contractions under conditions approximating those used in vivo (cycle frequency,
      1Hz; strain amplitude, +/- 10%L(0), where L(0) is the length giving maximum
      isometric force). During these experiments, work output was affected by
      stimulation phase, but did not depend on the longitudinal position in the body
      from which the muscles were taken. Our results indicate that red and white eel
      muscles have uniform properties along the body. In this respect, they differ from
      the muscle of most non-anguilliforms, in which muscle kinetics varies in a
      systematic way along the body. Uniform properties may be beneficial for
      anguilliform swimmers, in which the amplitude of the travelling wave can be
      pronounced over the entire body length.

PMID- 11507107
TI  - Fast muscle function in the European eel (Anguilla anguilla L.) during aquatic
      and terrestrial locomotion.
AB  - Eels are capable of locomotion both in water and on land using undulations of the
      body axis. Axial undulations are powered by the lateral musculature. Differences
      in kinematics and the underlying patterns of fast muscle activation are apparent
      between locomotion in these two environments. The change in isometric fast muscle
      properties with axial location was less marked than in most other species. Time
      from stimulus to peak force (T(a)) did not change significantly with axial
      position and was 82+/-6 ms at 0.45BL and 93+/-3 ms at 0.75BL, where BL is total
      body length. Time from stimulus to 90% relaxation (T(90)) changed significantly
      with axial location, increasing from 203+/-11ms at 0.45BL to 239+/-9 ms at
      0.75BL. Fast muscle power outputs were measured using the work loop technique.
      Maximum power outputs at +/-5% strain using optimal stimuli were 17.3+/-1.3W kg(
      1) in muscle from 0.45BL and 16.3+/-1.5W kg(-1) in muscle from 0.75BL. Power
      output peaked at a cycle frequency of 2Hz. The stimulus patterns associated with
      swimming generated greater force and power than those associated with terrestrial
      crawling. This decrease in muscle performance in eels may occur because on land
      the eel is constrained to a particular kinematic pattern in order to produce
      thrust against an underlying substratum.

PMID- 11507108
TI  - Spatial variation in fast muscle function of the rainbow trout Oncorhynchus
      mykiss during fast-starts and sprinting.
AB  - Fish fast-starts and sprints are rapid kinematic events powered by the lateral
      myotomal musculature. A distinction can be made between fast-starts and sprint
      swimming activity. Fast-starts are kinematic events involving rapid, asymmetrical
      movements. Sprints involve a series of symmetrical, high-frequency tailbeats that
      are kinematically similar to lower-frequency, sustained swimming. The patterns of
      muscle recruitment and strain associated with these swimming behaviours were
      determined using electromyography and sonomicrometry. Axial patterns of fast
      muscle recruitment during sprints were similar to those in slow muscle in that
      the duration of electromyograhic (EMG) activity decreased in a rostro-caudal
      direction. There was also an axial shift in activity relative to the strain cycle
      so that activity occurred relatively earlier in the caudal region. This may
      result in caudal muscle performing a greater proportion of negative work and
      acting as a power transmitter as well as a power producer. The threshold tailbeat
      frequency for recruitment of fast muscle differed with location in the myotome.
      Superficial muscle fibres were recruited at lower tailbeat frequencies and
      shortening velocities than those deeper in the musculature. During sprints, fast
      muscle strain ranged from +/- 3.4% l(0) (where l(0) is muscle resting length) at
      0.35FL (where FL is fork length) to +/- 6.3% l(0) at 0.65FL. Fast-starts involved
      a prestretch of up to 2.5% l(0) followed by shortening of up to 11.3% l(0). Stage
      1 EMG activity began simultaneously, during muscle lengthening, at all axial
      locations. Stage 2 EMG activity associated with the major contralateral
      contraction also commenced during lengthening and proceeded along the body as a
      wave. Onset of muscle activity during lengthening may enhance muscle power
      output.

PMID- 11507109
TI  - Locomotion in scombrid fishes: visualization of flow around the caudal peduncle
      and finlets of the chub mackerel Scomber japonicus.
AB  - Scombrid fishes are known for high-performance locomotion; however, few data are
      available on scombrid locomotor hydrodynamics. In this paper, we present flow
      visualization data on patterns of water movement over the caudal peduncle and
      finlets (small fins on the dorsal and ventral body margin anterior to the caudal
      fin). Chub mackerel, Scomber japonicus, ranging in fork length from 20 to 26 cm,
      swam steadily at 1.2forklengthss(-1) in a recirculating flow tank. Small,
      reflective particles in the flow tank were illuminated by a vertical (xy) or
      horizontal (xz) laser light sheet. Patterns of flow in the region near the caudal
      peduncle were measured using digital particle image velocimetry. Patterns of flow
      along the peduncle and finlets were quantified using manual particle tracking;
      more than 800 particles were tracked for at least 12ms over a series of tailbeats
      from each of four fish. In the vertical plane, flow trajectory and flow speed
      were independent of the position of the finlets, indicating that the finlets did
      not redirect flow or affect flow speed. Along, above and below the trailing
      surface of the peduncle, where the finlets were oriented along the peduncular
      surface, flow was convergent. Along, above and below the leading surface of the
      peduncle, where the finlets were absent, the flow trajectory was effectively
      horizontal. The lack of divergent flow on the leading surface of the peduncle is
      consistent with cross-peduncular flow formed by the lateral motion of the
      peduncle interacting with convergent flow resulting from forward movement of the
      body. In the horizontal plane, particles illuminated by the xz light sheet
      situated approximately 3 mm below the ventral body surface were tracked within
      the laser light sheet for up to 40ms, indicating strong planar flow. As the
      peduncle decelerates, the most posterior finlet is frequently at an angle of
      attack of at least 20 degrees to the incident flow, but this orientation does not
      result in thrust production from lift generation. Finlet 5 does redirect cross
      peduncular flow and probably generates small vortices undetectable in this study.
      These data are the first direct demonstration that the finlets have a
      hydrodynamic effect on local flow during steady swimming.

PMID- 11507110
TI  - Physiological characterisation of antennal mechanosensory descending interneurons
      in an insect (Gryllus bimaculatus, Gryllus campestris) brain.
AB  - We investigated five different descending brain interneurons with dendritic
      arborizations in the deutocerebrum in the crickets Gryllus bimaculatus and G.
      campestris. These interneurones convey specific antennal mechanosensory
      information to the ventral nerve cord and all responded to forced antennal
      movements. These interneurones coded for velocity and showed preferences for
      distinct sectors of the total range of antennal movements. Their axons descended
      into the posterior connective either ipsilateral or contralateral to the cell
      body. Electrical stimulation of sensory nerves indicated that the interneurons
      received input from different afferents of the two antennal base segments. One
      interneuron had a particularly large axon with a conduction velocity of 4.4 ms(
      1). This was the only one of the five interneurons that also received visual
      input. Its activity was reduced during voluntary antennal movements. The
      reduction in activity occurred even after de-efferentation of the antenna,
      indicating that it had a central origin. Although we do not have experimental
      evidence for behavioural roles for the descending antennal mechanosensory
      interneurons, the properties described here suggest an involvement in the
      perception of objects in the path of the cricket.

PMID- 11507111
TI  - Swing- and support-related muscle actions differentially trigger human walk-run
      and run-walk transitions.
AB  - There has been no consistent explanation as to why humans prefer changing their
      gait from walking to running and from running to walking at increasing and
      decreasing speeds, respectively. This study examined muscle activation as a
      possible determinant of these gait transitions. Seven subjects walked and ran on
      a motor-driven treadmill for 40s at speeds of 55, 70, 85, 100, 115, 130 and 145%
      of the preferred transition speed. The movements of subjects were videotaped, and
      surface electromyographic activity was recorded from seven major leg muscles.
      Resultant moments at the leg joints during the swing phase were calculated.
      During the swing phase of locomotion at preferred running speeds (115, 130,
      145%), swing-related activation of the ankle, knee and hip flexors and peaks of
      flexion moments were typically lower (P<0.05) during running than during walking.
      At preferred walking speeds (55, 70, 85%), support-related activation of the
      ankle and knee extensors was typically lower during stance of walking than during
      stance of running (P<0.05). These results support the hypothesis that the
      preferred walk-run transition might be triggered by the increased sense of effort
      due to the exaggerated swing-related activation of the tibialis anterior, rectus
      femoris and hamstrings; this increased activation is necessary to meet the higher
      joint moment demands to move the swing leg during fast walking. The preferred run
      walk transition might be similarly triggered by the sense of effort due to the
      higher support-related activation of the soleus, gastrocnemius and vastii that
      must generate higher forces during slow running than during walking at the same
      speed.

PMID- 11507112
TI  - Analysis of epithelial K(+) transport in Malpighian tubules of Drosophila
      melanogaster: evidence for spatial and temporal heterogeneity.
AB  - Transport of K(+) by the lower, main and distal segments of the Malpighian
      tubules of Drosophila melanogaster was analyzed using self-referencing K(+)
      selective microelectrodes. Transport properties of the Malpighian tubules of
      Drosophila melanogaster change along their length. Self-referencing ion-selective
      (SeRIS) microelectrode measurements (relative to the bath concentration of 20
      mmoll(-1)) showed a 1% reduction (P<0.05) of [K(+)] in the unstirred layer
      adjacent to the main segment of the Malpighian tubules, confirming secretion of
      K(+) from the bath to the tubule lumen. Conversely, SeRIS measurements showed a
      0.7% increase (P<0.05) in [K(+)] in the unstirred layer adjacent to the lower
      segment of Malpighian tubules, confirming reabsorption of K(+) from the luminal
      fluid to the bath. Measurements using SeRIS also showed that the distal segment
      neither secreted nor reabsorbed K(+). There was pronounced spatial heterogeneity
      in K(+) transport by the lower segment and the main segment; not all
      morphologically similar cells participated equally in K(+) transport, nor did all
      main segment cells respond equally to stimulation of K(+) transport by cyclic
      AMP. Pronounced temporal heterogeneity in K(+) reabsorption by the lower
      Malpighian tubules was also observed. We suggest that this reflects periodic
      reduction in K(+) reabsorption due to retention of fluid within the lower segment
      when the ureter contracts.

PMID- 11507113
TI  - Seasonal variation in energy expenditure, water flux and food consumption of
      Arabian oryx Oryx leucoryx.
AB  - We report on the energy expenditure and water flux, measured in the laboratory
      and in the field, of the Arabian oryx Oryx leucoryx, the largest desert ruminant
      for which measurements of the field metabolic rate of free-living individuals
      have been made using doubly labeled water. Prior to extirpation of this species
      in the wild in 1972, conservationists sequestered a number of individuals for
      captive breeding; in 1989, oryx were reintroduced in Saudi Arabia into Mahazat as
      Sayd (2244 km(2)). Apart from small pools of water available after rains, oryx do
      not have free-standing water available for drinking and therefore rely on grasses
      that they eat for preformed water intake as well as their energy needs. We tested
      whether oryx have a reduced fasting metabolic rate and total evaporative water
      loss (TEWL) in the laboratory, as do some other arid-adapted mammals, and whether
      oryx have high field metabolic rates (FMRs) and water influx rates (WIRs), as
      predicted by allometric equations for large arid-zone mammals. We measured FMR
      and WIR during the hot summer, when plant moisture content was low and ambient
      temperatures were high, and after winter rains, when the water content of grasses
      was high. For captive oryx that weighed 84.1 kg, fasting metabolic rate averaged
      8980 kJ day(-1), 16.7% lower than predictions for Artiodactyla. Our own re
      analysis of minimal metabolic rates among Artiodactyla yielded the equation:
      logV(O2)=-0.153+0.758logM, where V(O2) is the rate of oxygen uptake in lh(-1) and
      M is body mass in kg. Fasting metabolic rate of oryx was only 9.1% lower than
      predicted, suggesting that they do not have an unusually low metabolic rate. TEWL
      averaged 870.0 ml day(-1), 63.9% lower than predicted, a remarkably low value
      even compared with the camel, but the mechanisms that contribute to such low
      rates of water loss remain unresolved. For free-living oryx, FMR was 11076 kJ
      day(-1) for animals with a mean body mass of 81.5 kg during summer, whereas it
      was 22081 kJ day(-1) for oryx in spring with a mean body mass of 89.0 kg, values
      that were 48.6% and 90.4% of allometric predictions, respectively. During summer,
      WIR averaged 1310 ml H(2)O day(-1), whereas in spring it was 3438 ml H(2)O day(
      1). Compared with allometric predictions, WIR was 76.9% lower than expected in
      summer and 43.6% lower in spring. We found no evidence to support the view that
      the WIR of large desert ungulates is higher than that of their mesic
      counterparts. On the basis of the WIR of the oryx averaged over the year and the
      water contents of plants in their diet, we estimated that an oryx consumes 858 kg
      of dry matter per year.

PMID- 11507114
TI  - A qualitative and quantitative study of the lung of an ostrich, Struthio camelus.
AB  - The ostrich lung, with its lack of interparabronchial septa, the presence of very
      shallow atria and exceptional morphometric refinement, structurally resembles
      those of small, energetic flying birds, whereas it also displays features
      characteristic of the flightless ratites in which the neopulmo is relatively
      poorly developed and a segmentum accelerans may be generally lacking. The large
      size of the bronchial system of the ostrich may help explain the unique shifts in
      the airflow pathways that must occur from resting to panting breathing,
      explaining its insensitivity to acid-base imbalance of the blood during sustained
      panting under thermal stress. The mass-specific volume of the lung is 39.1
      cm(3)kg(-1) and the volume density of the exchange tissue is remarkably high
      (78.31%). The blood-gas (tissue) barrier is relatively thick (0.56 microm) but
      the plasma layer is very thin (0.14 microm). In this flightless ratite bird, the
      mass-specific surface area of the tissue barrier (30.1 cm(2)g(-1)), the mass
      specific anatomical diffusing capacity of the tissue barrier for oxygen (0.00 22
      ml O(2) s(-1) Pa(-1) kg(-1)), the mass-specific volume of pulmonary capillary
      blood (6.25 cm(3)kg(-1)) and the mass-specific total anatomical diffusing
      capacity for oxygen (0.00073 ml O(2) s(-1) Pa(-1) kg(-1)) are equivalent to or
      exceed those of much smaller highly aerobic volant birds. The distinctive
      morphological and morphometric features that seem to occur in the ostrich lung
      may explain how it achieves and maintains high aerobic capacities and endures
      long thermal panting without experiencing respiratory alkalosis.

PMID- 11507115
TI  - Evolution of water balance in the genus Drosophila.
AB  - Fruit flies of the genus Drosophila have independently invaded deserts around the
      world on numerous occasions. To understand the physiological mechanisms allowing
      these small organisms to survive and thrive in arid environments, we performed a
      phylogenetic analysis of water balance in Drosophila species from different
      habitats. Desert (cactophilic) species were more resistant to desiccation than
      mesic ones. This resistance could be accomplished in three ways: by increasing
      the amount of water in the body, by reducing rates of water loss or by tolerating
      the loss of a greater percentage of body water (dehydration tolerance).
      Cactophilic Drosophila lost water less rapidly and appeared to be more tolerant
      of low water content, although males actually contained less water than their
      mesic congeners. However, when the phylogenetic relationships between the species
      were taken into account, greater dehydration tolerance was not correlated with
      increased desiccation resistance. Therefore, only one of the three expected
      adaptive mechanisms, lower rates of water loss, has actually evolved in desert
      Drosophila, and the other apparently adaptive difference between arid and mesic
      species (increased dehydration tolerance) instead reflects phylogenetic history.

PMID- 11507116
TI  - Nuclear p26, a small heat shock/alpha-crystallin protein, and its relationship to
      stress resistance in Artemia franciscana embryos.
AB  - The role of the small heat shock/alpha-crystallin protein, p26, in transcription
      in Artemia franciscana embryos was examined using isolated nuclei, containing
      either control or elevated levels of p26, in transcription run-on assays. Heat
      shock or anoxia in vivo and acid pH in vitro were used to transfer p26 into
      nuclei. The results suggest that parameters other than, or in addition to, p26
      are responsible for the reduced transcription rates observed and that decreases
      in pHi are involved. In vivo experiments indicate that RNA synthesis and, to a
      lesser extent, protein synthesis are downregulated in intact embryos recovering
      from heat shock and that the precursor pool is not limiting. Confocal microscopy
      confirmed that p26 moves into nuclei in response to heat shock and anoxia in
      vivo, and to low pH in vitro, and indicated that the nuclear distribution of p26
      is similar under all three conditions. We present evidence that unstressed
      (control) embryos containing p26 in all their nuclei will not hatch, even under
      permissive conditions, and propose that they are unable to terminate diapause.
      Potential nuclear targets of p26 chaperone activity are discussed.

PMID- 11507117
TI  - Nutritional regulation and tissue specificity of gene expression for proteins
      involved in hepatic glucose metabolism in rainbow trout (Oncorhynchus mykiss).
AB  - Rainbow trout (Oncorhynchus mykiss) are known to use dietary carbohydrates
      poorly. One of the hypotheses to explain the poor utilisation of dietary glucose
      by these fish is a dysfunction in nutritional regulation of hepatic glucose
      metabolism. In this study, we obtained partial clones of rainbow trout cDNAs
      coding for a glucose transporter (Glut2), and for the enzymes 6-phosphofructo-2
      kinase/fructose-2,6-bisphosphatase (6PF-2K/F-2,6BPase), fructose-1,6
      bisphosphatase (FBPase) and pyruvate kinase (PK). Their deduced amino acid
      sequences were highly similar to those of mammals (up to 80% similarity). In a
      study of nutritional regulation, the Glut2 gene was highly expressed in the liver
      irrespective of the nutritional status of the trout, in agreement with the role
      of this transporter in the input (during refeeding) and output (during fasting)
      of glucose from the liver. Moreover, whereas PK and FBPase gene expression was
      high irrespective of the nutritional status, levels of hepatic 6PF-2K/F-2,6BPase
      mRNA were higher in fish fed with carbohydrates than in fish deprived of food.
      The high levels of hepatic PK, Glut2 and 6PF-2K/F-2,6BPase gene expression
      observed in this study suggest a high potential for tissue carbohydrate
      utilisation in rainbow trout. The persistence of a high level of FBPase gene
      expression suggests an absence of regulation of the gluconeogenic pathway by
      dietary carbohydrates.

PMID- 11507118
TI  - Impact of movement and movement-related feedback on the lamprey central pattern
      generator for locomotion.
AB  - A semi-reduced, minimally restrained lamprey preparation was used to investigate
      the impact of movement and movement-related feedback during D-glutamate-induced
      locomotion. The preparation consisted of the trunk alone with the spinal cord
      exposed to the bathing solution. Two conditions were compared using
      electromyography or nerve recording: (i) muscle and spinal cord, (ii) spinal cord
      alone supported by the notochord. Compared with the isolated spinal cord,
      movement in the presence of muscle consistently and significantly increased the
      frequency of the motor output and reduced the phase delay among the segments. In
      moving preparations, coupling among the segments was reduced by two staggered
      hemisections to permit the strength and direction of intersegmental coupling to
      be estimated. The estimates revealed that movement increased the total
      intersegmental coupling strength and increased the proportion of the coupling
      that was descending over those of the isolated spinal cord. The effects on the
      phase and frequency of bursting can be explained in the light of the excitation
      evoked by bending that we have reported previously. Thus, we demonstrate that
      movement and movement-related feedback that arise from spinally induced motor
      patterns can alter the form of the movement and the functional coupling strength
      among the segments of the lamprey spinal cord.

PMID- 11507119
TI  - Function of the oblique hypaxial muscles in trotting dogs.
AB  - In trotting dogs, the pattern of activity of the obliquely oriented hypaxial
      muscles is consistent with the possible functions of (i) stabilization against
      vertical accelerations that cause the trunk to sag in the sagittal plane and (ii)
      stabilization against forces that tend to shear the trunk in the sagittal plane.
      To test these hypotheses, we compared the amount of activity of the intercostal
      and abdominal oblique muscles (i) when dogs carried additional mass (8-15% of
      body mass) supported over the limb girdles versus supported mid-trunk (test of
      sagittal bounce), and (ii) when dogs trotted up versus down a 10 degrees slope
      (test of sagittal shear). In response to the loading manipulations, only the
      internal oblique muscle responded in a manner that was consistent with
      stabilization of the trunk against forces that cause the trunk to sag sagittally.
      In contrast, when the fore-aft forces were manipulated by running up- and
      downhill, all four of the monitored muscles changed their activity in a manner
      consistent with stabilization of the trunk against sagittal shearing.
      Specifically, muscles with a craniodorsal orientation (external oblique and
      external intercostal muscles) showed an increase in activity when the dogs ran
      downhill and a decrease when they ran uphill. Muscles with a cranioventral
      orientation (internal oblique and internal intercostal muscles) exhibited the
      opposite pattern: increased activity when the dogs ran uphill and decreased
      activity when they ran downhill. Changes in activity of two extrinsic
      appendicular muscles, the serratus ventralis and deep pectoralis, during uphill
      and downhill running were also consistent with the sagittal shearing hypothesis.
      In contrast, changes in the level of recruitment of the oblique hypaxial muscles
      were not consistent with stabilization of the trunk against torques that induce
      yaw at the girdles. Hence, we suggest that the oblique hypaxial muscles of
      trotting dogs act to stabilize the trunk against sagittal shearing torques
      induced by limb retraction (fore-aft acceleration) and protraction (fore-aft
      deceleration).

PMID- 11507120
TI  - Revision anterior cruciate surgery with use of bone-patellar tendon-bone
      autogenous grafts.
AB  - BACKGROUND: A prospective study was done to determine the functional results,
      patient satisfaction, and graft failure rate after fifty-seven consecutive
      revision replacements of the anterior cruciate ligament with use of a bone
      patellar tendon-bone autogenous graft. METHODS: Fifty-four patients (fifty-five
      operations) were followed in this study. Concurrent operative procedures were
      performed during the revision procedure in thirty-seven knees (67%). These
      procedures included repair of a meniscal tear in twenty knees (36%) and
      reconstruction of deficient posterolateral or medial ligament structures in
      seventeen knees (31%). Nine knees (16%) had a high tibial osteotomy to correct
      varus malalignment before the revision operation. The results were evaluated with
      the Cincinnati Knee Rating System. RESULTS: There were significant improvements
      in the scores for pain (p < 0.0001), activities of daily living (p < 0.01),
      sports participation (p < 0.001), patient satisfaction (p < 0.0001), and overall
      rating of the knee (p < 0.0001). Thirty-three (60%) of the replaced ligaments
      were functional, nine (16%) were partially functional, and thirteen (24%) had
      failed. CONCLUSIONS: Many knees (93%) had compounding problems, including
      articular cartilage damage, prior meniscectomy, loss of secondary ligament
      restraints, varus malalignment, and concomitant ligament replacement or meniscal
      repair. Therefore, the results were generally less favorable than those following
      primary operations. The rate of graft failure was three times higher than our
      previously reported failure rate after primary replacements of the anterior
      cruciate ligament with a bone-patellar tendon-bone autogenous graft. Even so,
      symptoms and functional limitations with regard to daily and sports activities
      were found to have decreased and patient satisfaction improved. We advocate
      correction of varus malalignment prior to anterior cruciate procedures.
      Associated posterolateral ligament deficiencies should be surgically corrected
      during anterior cruciate procedures to prevent excessive loading on the graft
      from abnormal lateral tibiofemoral joint opening. Meniscal tears, including
      complex tears that extend into the avascular zone, can be concurrently repaired
      successfully during the revision.

PMID- 11507121
TI  - Total knee arthroplasty after open reduction and internal fixation of fractures
      of the tibial plateau: a minimum five-year follow-up study.
AB  - BACKGROUND: There is little information in the literature regarding the outcome
      of total knee arthroplasty following open reduction and internal fixation of
      fractures of the tibial plateau. The goal of this study was to evaluate the
      results of such procedures after a minimum of five years of follow-up. METHODS:
      We retrospectively analyzed the outcomes of fifteen total knee arthroplasties
      performed at an average of 38.6 months (range, eight months to eleven years)
      after open reduction and internal fixation of a fracture of the tibial plateau in
      fifteen consecutive patients. The average duration of follow-up after the total
      knee arthroplasty procedures was 6.2 years (range, 5.4 to 11.1 years). The
      average age of the patients was fifty-six years (range, thirty-seven to sixty
      eight years) at the time of the arthroplasty. We evaluated the outcomes on the
      basis of the Hospital for Special Surgery knee score, the Short Form-36 score,
      and radiographs of the knees. RESULTS: The average Hospital for Special Surgery
      knee score was 51 points (range, 20 to 74 points) before the arthroplasty, and it
      increased to 80 points (range, 44 to 91 points) postoperatively. Four knees were
      scored as excellent, eight had a good result, one was rated as fair, and two had
      a poor result. The average Short Form-36 scores were 58.0 points for general
      health, 72.4 points for bodily pain, 72.1 points for mental health, 58.3 points
      for physical functioning, 84.6 points for physical role functioning, 81.0 points
      for social functioning, and 57.7 points for vitality. The average active
      postoperative arc of motion was 105 degrees (range, 70 degrees to 135 degrees )
      compared with 87 degrees (range, 20 degrees to 125 degrees ) preoperatively.
      Incomplete radiolucencies were noted on all of the postoperative radiographs made
      after the total knee arthroplasties. There was a high rate of infection (three
      patients), patellar tendon disruption (two patients), and postoperative secondary
      procedures (three patients required closed manipulation). The patients with
      infection were considered to have a failure of treatment: two required
      arthrodesis, and one required a two-stage exchange. CONCLUSION: On the basis of
      our results, we concluded that total knee arthroplasty after open reduction and
      internal fixation of a fracture of the tibial plateau decreases pain and improves
      knee function, but the procedure is technically demanding and is associated with
      a high failure rate (five of fifteen).

PMID- 11507123
TI  - Thirty-day mortality after total knee arthroplasty.
AB  - BACKGROUND: There have been sporadic reports on perioperative mortality
      associated with total knee arthroplasty. The purpose of this study was to
      determine risk factors for such mortality. METHODS: A computer-assisted review of
      the records of 22,540 consecutive patients who had undergone total knee
      arthroplasty between 1969 and 1997 was performed to identify all patients who had
      died within thirty days after the procedure. A detailed analysis of the medical,
      surgical, anesthetic, and pathological records of the patients was performed, and
      the mortality was determined according to age, gender, diagnosis, and fixation
      method. RESULTS: The rate of mortality within thirty days after the operation was
      0.21% (forty-seven of 22,540). All deaths occurred in the group of 18,810
      patients who had received a cemented implant, and no deaths occurred among the
      3730 patients who had received an uncemented implant (p < 0.0001). The mortality
      rate was 0.24% (forty-three of 18,165) after primary arthroplasty and 0.09% (four
      of 4375) after revision arthroplasty (p < 0.0003). Three patients (0.01%) died
      during the operation. Forty-three of the forty-seven patients who died had a
      history of preexisting cardiovascular and/or pulmonary disease. Simultaneous
      bilateral total knee arthroplasty was associated with a significantly higher rate
      of perioperative mortality (p < 0.002). CONCLUSIONS: Factors that were associated
      with a significantly increased mortality after total knee arthroplasty included
      an age of more than seventy years, primary (as compared with revision) knee
      surgery, use of a cemented prosthesis, preexisting cardiopulmonary disease, and
      simultaneous bilateral arthroplasty.

PMID- 11507122
TI  - Pitfalls of using patient recall to derive preoperative status in outcome studies
      of total knee arthroplasty.
AB  - BACKGROUND: It is essential to adjust for the level of preoperative pain and
      functional status when measuring the outcome of total knee arthroplasty. Some
      study designs rely on postoperative patient recall to derive preoperative status.
      In this study, we compared prospectively collected preoperative data with data
      derived from patient recall of preoperative status three months after total knee
      arthroplasty. METHODS: Patients were recruited as part of a prospective
      observational study of the outcome of primary total knee arthroplasty for
      osteoarthritis at four centers in the United States, six centers in the United
      Kingdom, and two centers in Australia. Independent research assistants recruited
      patients and collected data with use of a uniform documentation system
      preoperatively and three months postoperatively. Preoperative data included the
      findings of a clinical history and physical examination, demographic information,
      socioeconomic status, and scores from two health-status instruments: the Western
      Ontario and McMaster University Osteoarthritis Index (WOMAC) and the Medical
      Outcomes Study Short Form-36 Health Survey (SF-36). Postoperative data included
      the WOMAC and SF-36 scores and patient recall of preoperative status on selected
      items from these health-status measures. RESULTS: A total of 862 patients were
      recruited, and recall data were available for 770 patients (89%). The mean age
      was seventy years (range, thirty-eight to ninety years), and 59% of the patients
      were women. Comparisons of prospective and recall data on individual pain and
      function items showed poor-to-fair agreement (weighted kappa, 0.20 to 0.41).
      Patients recalled significantly more pain than they had reported preoperatively
      (p < 0.001), but there were random recollection errors for the function items.
      There was only moderate correlation between the prospective and recalled summary
      scores for pain (Spearman r = 0.53) and function (Spearman r = 0.48). In
      addition, 61% of the recalled pain scores and 50% of the recalled function scores
      differed from the prospective scores by more than 10 points (10% of the total
      range). CONCLUSIONS: Patients' recall of preoperative pain and functional status
      three months after total knee arthroplasty demonstrated only moderate agreement
      with what the patients had reported prospectively. Researchers who use recall
      data to derive preoperative status must recognize these limitations when drawing
      conclusions about the effectiveness of total knee arthroplasty.

PMID- 11507124
TI  - Pulmonary dysfunction in patients with femoral shaft fracture treated with
      intramedullary nailing.
AB  - BACKGROUND: This study was undertaken to determine whether alveolar dead space
      increases during intramedullary nailing of femoral shaft fractures and whether
      alveolar dead space predicts postoperative pulmonary dysfunction in patients
      undergoing intramedullary nailing of a femoral shaft fracture. METHODS: All
      patients with a femoral shaft fracture were prospectively enrolled in the study
      unless there was evidence of acute myocardial infarction, shock, or heart
      failure. Arterial blood gases were measured at three consecutive time-periods
      after induction of general anesthesia: before intramedullary nailing and ten and
      thirty minutes after intramedullary nailing. The end-tidal carbon-dioxide level,
      minute ventilation, positive end-expiratory pressure, and percent of inspired and
      expired inhalation agent were recorded simultaneously with the blood-gas
      measurement. Postoperatively, all subjects were monitored for evidence of
      pulmonary dysfunction, defined as the need for mechanical ventilation or
      supplemental oxygen (at a fraction of inspired oxygen of >40%) in the presence of
      clinical signs of a respiratory rate of >20 breaths/min or the use of accessory
      muscles of respiration. RESULTS: Seventy-four patients with a total of eighty
      femoral shaft fractures completed the study. Fifty fractures (62.5%) underwent
      nailing after reaming, and thirty fractures (37.5%) underwent nailing with
      minimal or no reaming. The mean alveolar dead-space measurements before canal
      opening and at ten and thirty minutes after canal opening were 14.5%, 15.8%, and
      15.2% in the total series of seventy-four patients (general linear model, p =
      0.2) and 20.5%, 22.7%, and 24.2% in the twenty patients with postoperative
      pulmonary dysfunction (general linear model, p = 0.05). Of the twenty-one
      patients with an alveolar dead-space measurement of >20% thirty minutes after
      nailing, sixteen had postoperative pulmonary dysfunction. According to univariate
      and multivariate analysis, the alveolar dead-space measurement was strongly
      associated with postoperative pulmonary dysfunction. CONCLUSIONS: According to
      our data, intramedullary nailing of femoral shaft fractures did not significantly
      increase alveolar dead space, and the amount of alveolar dead space can predict
      which patients will have pulmonary dysfunction postoperatively.

PMID- 11507125
TI  - Adolescent idiopathic scoliosis: a new classification to determine extent of
      spinal arthrodesis.
AB  - BACKGROUND: The lack of a reliable, universally acceptable system for
      classification of adolescent idiopathic scoliosis has made comparisons between
      various types of operative treatment an impossible task. Furthermore, long-term
      outcomes cannot be determined because of the great variations in the description
      of study groups. METHODS: We developed a new classification system with three
      components: curve type (1 through 6), a lumbar spine modifier (A, B, or C), and a
      sagittal thoracic modifier (-, N, or +). The six curve types have specific
      characteristics, on coronal and sagittal radiographs, that differentiate
      structural and nonstructural curves in the proximal thoracic, main thoracic, and
      thoracolumbar/lumbar regions. The lumbar spine modifier is based on the
      relationship of the center sacral vertical line to the apex of the lumbar curve,
      and the sagittal thoracic modifier is based on the sagittal curve measurement
      from the fifth to the twelfth thoracic level. A minus sign represents a curve of
      less than +10 degrees, N represents a curve of 10 degrees to 40 degrees, and a
      plus sign represents a curve of more than +40 degrees. Five surgeons, members of
      the Scoliosis Research Society who had developed the new system and who had
      previously tested the reliability of the King classification on radiographs of
      twenty-seven patients, measured the same radiographs (standing coronal and
      lateral as well as supine side-bending views) to test the reliability of the new
      classification. A randomly chosen independent group of seven surgeons, also
      members of the Scoliosis Research Society, tested the reliability and validity of
      the classification as well. RESULTS: The interobserver and intraobserver kappa
      values for the curve type were, respectively, 0.92 and 0.83 for the five
      developers of the system and 0.740 and 0.893 for the independent group of seven
      scoliosis surgeons. In the independent group, the mean interobserver and
      intraobserver kappa values were 0.800 and 0.840 for the lumbar modifier and 0.938
      and 0.970 for the sagittal thoracic modifier. These kappa values were all in the
      good-to-excellent range (>0.75), except for the interobserver reliability of the
      independent group for the curve type (kappa = 0.74), which fell just below this
      level. CONCLUSIONS: This new two-dimensional classification of adolescent
      idiopathic scoliosis, as tested by two groups of surgeons, was shown to be much
      more reliable than the King system. Additional studies are necessary to determine
      the versatility, reliability, and accuracy of the classification for defining the
      vertebrae to be included in an arthrodesis.

PMID- 11507126
TI  - The floating shoulder: a biomechanical basis for classification and management.
AB  - BACKGROUND: The floating shoulder (ipsilateral fractures of the clavicular shaft
      and the scapular neck) is thought to be an unstable injury pattern requiring
      operative stabilization in most instances. This recommendation has been made with
      little biomechanical data to support it. The purpose of this study was to
      determine the osseous and ligamentous contributions to the stability of
      experimentally created scapular neck fractures in a cadaver model. METHODS:
      Standardized scapular neck fractures were made in twelve fresh-frozen human
      cadaveric shoulders. Each specimen was mounted in a specially designed testing
      apparatus and secured to a standard materials testing device. In group 1 (six
      shoulders), resistance to medial displacement was determined following sequential
      creation of an ipsilateral clavicular fracture, coracoacromial ligament
      disruption, and acromioclavicular capsular disruption. In group 2 (six
      shoulders), resistance to medial displacement was determined following sequential
      sectioning of the coracoacromial and coracoclavicular ligaments. RESULTS: The
      average measured force for all specimens (groups 1 and 2) after scapular neck
      fracture was 183 +/- 3.3 N (range, 166 to 203 N). The addition of a clavicular
      fracture (group 1) resulted in an average measured force of 128 +/- 10.5 N
      (range, 83 to 153 N), which corresponds to only a 30% loss of stability.
      Subsequent sectioning of the coracoacromial and acromioclavicular capsular
      ligaments yielded an average force of 126 +/- 9.1 N (range, 114 to 144 N), a 31%
      loss of stability, and 0 N, a complete loss of stability, respectively.
      Sectioning of the coracoacromial and coracoclavicular ligaments after scapular
      neck fracture (group 2) resulted in an average force of 103 +/- 8.4 N (range, 89
      to 118 N), a 44% loss of stability, and 0 N, a complete loss of stability,
      respectively. CONCLUSIONS: Ipsilateral fractures of the scapular neck and the
      clavicular shaft do not produce a floating shoulder without additional disruption
      of the coracoacromial and acromioclavicular capsular ligaments. These and other
      unstable combined injury patterns are likely to be accompanied by substantial
      medial displacement of the glenoid fragment.

PMID- 11507127
TI  - The floating shoulder: clinical and functional results.
AB  - BACKGROUND: Displaced ipsilateral fractures of the clavicle and the glenoid neck
      are a complex injury pattern that is usually the result of high-energy trauma.
      The treatment of these injuries is controversial, as good results have been
      reported with both operative and nonoperative treatment. METHODS: Nineteen
      patients who had sustained a displaced fracture of the glenoid neck with an
      ipsilateral clavicular fracture or acromioclavicular separation (floating
      shoulder) were retrospectively evaluated. The treatment was nonoperative in
      twelve patients and operative in seven. At the time of final follow-up, standard
      radiographs were made and all patients were examined by a physical therapist and
      either a fellowship-trained shoulder surgeon or an orthopaedic traumatologist. In
      addition, each patient responded to three different validated objective
      functional outcome measures: the Short Form-36, the American Shoulder and Elbow
      Surgeons Shoulder Scale, and the Disabilities of the Arm, Shoulder and Hand
      Questionnaire. Isokinetic strength-testing was performed, and strength in
      internal and external rotation was compared with that of the uninvolved shoulder.
      The main outcome measures included fracture-healing, functional outcome, patient
      satisfaction, and muscular strength. RESULTS: With regard to range of motion,
      only the amount of forward flexion was found to be significantly greater in the
      operatively treated group (p = 0.03). The operatively treated shoulders were
      found to be weaker in external rotation at 300 degrees /sec and weaker in
      internal rotation at 180 degrees /sec. When normalized to hand dominance,
      however, the numbers were too small to identify any significant difference. There
      was no significant difference between groups with regard to the three functional
      outcome measures. CONCLUSIONS: Good results may be seen both with and without
      operative treatment. Therefore, we cannot universally recommend operative
      treatment for a double disruption of the superior suspensory shoulder complex.
      Treatment must be individualized for each patient.

PMID- 11507128
TI  - Regional osteoporosis in women who have a complete spinal cord injury.
AB  - BACKGROUND: Regional bone loss in patients who have a spinal cord injury has been
      evaluated in males. In addition, there have been reports on groups of patients of
      both genders who had an acute or chronic complete or incomplete spinal cord
      injury. Regional bone loss in females who have a complete spinal cord injury has
      not been reported, to our knowledge. METHODS: In a study of thirty-one women who
      had a chronic, complete spinal cord injury, we assessed bone mineral density in
      relation to age, weight, and time since the injury. The results were compared
      with the bone mineral density in seventeen healthy, able-bodied women who had
      been age-matched by group (thirty years old and less, thirty-one to fifty years
      old, and more than fifty years old). Dual-energy x-ray absorptiometry was used to
      measure the bone mineral density of the lumbar spine, hip, and knee; Z-scores for
      the hip and spine were calculated. RESULTS: The mean bone mineral density in the
      spine in the youngest, middle, and oldest spinal-cord-injury groups was 98%,
      108%, and 115% of the densities in the respective age-matched control groups (p <
      0.0001), and the mean bone mineral density in the oldest spinal-cord-injury group
      was equal to that in the youngest control group. This gain in bone mineral
      density in the spine was reflected by the spine Z-scores, as the mean score in
      the oldest injured group averaged more than one standard deviation above both the
      norm and the mean score in the control group. The mean loss of bone mineral
      density in the knee in the youngest, middle, and oldest spinal-cord-injury groups
      was 38%, 41%, and 47% compared with the densities in the corresponding control
      age-groups (p < 0.0001). Furthermore, the oldest injured group had a mean
      reduction of knee bone mineral density of 54% compared with the youngest control
      group. The mean loss of bone mineral density in the hips of the injured patients
      was 18%, 25%, and 25% compared with the densities in the control subjects in the
      respective age-groups (p < 0.0001). CONCLUSIONS: The bone mineral density in the
      spine either was maintained or was increased in relation to the time since the
      injury. This finding is unlike that seen in healthy women, in whom bone mineral
      density decreases with age. The bone mineral density in the hips of the injured
      patients initially decreased approximately 25%; thereafter, the rate of loss was
      similar to that in the control group. The bone mineral density in the knees of
      the injured patients rapidly decreased 40% to 45% and then further decreased only
      minimally.

PMID- 11507129
TI  - Arthroplasty with a metal radial head for unreconstructible fractures of the
      radial head.
AB  - BACKGROUND: Treatment of unreconstructible comminuted fractures of the radial
      head remains controversial. There is limited information on the outcome of
      management of these injuries with arthroplasty with a metal radial head implant.
      METHODS: The functional outcomes of arthroplasties with a metal radial head
      implant for the treatment of twenty-five displaced, unreconstructible fractures
      of the radial head in twenty-four consecutive patients (mean age, fifty-four
      years) were evaluated at a mean of thirty-nine months (minimum, two years). There
      were ten Mason type-III and fifteen Mason-Johnston type-IV injuries. Two of these
      injuries were isolated, and twenty-three were associated with other elbow
      fractures and/or ligamentous injuries. RESULTS: At the time of follow-up, Short
      Form-36 (SF-36) summary scores suggested that overall health-related quality of
      life was within the normal range (physical component = 47 +/- 10, and mental
      component = 49 +/- 13). Other outcome scales indicated mild disability of the
      upper extremity (Disabilities of the Arm, Shoulder and Hand score = 17 +/- 19),
      wrist (Patient-Rated Wrist Evaluation score = 17 +/- 21 and Wrist Outcome Score =
      60 +/- 10), and elbow (Mayo Elbow Performance Index = 80 +/- 16). According to
      the Mayo Elbow Performance Index, three results were graded as poor; five, as
      fair; and seventeen, as good or excellent. The poor and fair outcomes were
      associated with concomitant injury in two patients, a history of a psychiatric
      disorder in three, comorbidity in two, a Workers' Compensation claim in two, and
      litigation in one. Subjective patient satisfaction averaged 9.2 on a scale of 1
      to 10. Elbow flexion of the injured extremity averaged 140 degrees +/- 9 degrees;
      extension, -8 degrees +/- 7 degrees; pronation, 78 degrees +/- 9 degrees; and
      supination, 68 degrees +/- 10 degrees. A significant loss of elbow flexion and
      extension and of forearm supination occurred in the affected extremity, which
      also had significantly less strength of isometric forearm pronation (17%) and
      supination (18%) as well as significantly less grip strength (p < 0.05).
      Asymptomatic bone lucencies surrounded the stem of the implant in seventeen of
      the twenty-five elbows. Valgus stability was restored, and proximal radial
      migration did not occur. Complications, all of which resolved, included one
      complex regional pain syndrome, one ulnar neuropathy, one posterior interosseous
      nerve palsy, one episode of elbow stiffness, and one wound infection.
      CONCLUSIONS: Patients treated with a metal radial head implant for a severely
      comminuted radial head fracture will have mild-to-moderate impairment of the
      physical capability of the elbow and wrist. At the time of short-term follow-up,
      arthroplasty with a metal radial head implant was found to have been a safe and
      effective treatment option for patients with an unreconstructible radial head
      fracture; however, long-term follow-up is still needed.

PMID- 11507130
TI  - Growth and development of the pediatric cervical spine documented
      radiographically.
AB  - BACKGROUND: The radiographic anatomy of the cervical spine in children is complex
      and can be difficult to interpret. The present study was undertaken to document
      radiographically the growth and development of the cervical spine in a
      prospective, longitudinal manner and to establish standard radiographic
      measurements on the basis of findings in patients who were followed serially from
      the age of three months until skeletal maturity. METHODS: The radiographic
      resources of the Cleveland Study of Normal Growth and Development (Bolton-Brush
      Collection, Cleveland, Ohio) were reviewed. From this large database, we
      identified fifty boys and forty-six girls who had a sufficient number of
      radiographs of the cervical spine for inclusion in our study. With use of a
      computerized image analyzer, the growth and development of the atlantodens
      interval, the diameter of the spinal canal, the Torg ratio, the height and width
      of the second through fifth cervical vertebral bodies, the height of the dens,
      and the ossification of the first cervical vertebra were assessed on serial
      radiographs made from the age of three months until skeletal maturity. RESULTS:
      Serial measurements of the atlantodens interval, the anteroposterior diameter of
      the cervical canal, the height and anteroposterior width of the cervical
      vertebral bodies, and the height of the dens, made in normal, healthy children
      from the age of three months to fifteen years, are presented in tabular and
      graphic forms. The median Torg ratio was 1.47 for both males and females
      primarily, and it reached values of 1.06 for males and 1.10 for females by
      maturity. The anterior arch of the first cervical vertebra had ossified in 33% of
      the children by the age of three months and in 81% of the children by the age of
      one year. Closure of the synchondroses was completed in all children by the age
      of three years. CONCLUSIONS: The measurements presented in the current study are
      important because they are the first, as far as we know, to document the
      radiographic parameters of the cervical spine in children who were followed
      longitudinally from before the age of three years through the course of growth
      and development until skeletal maturity.

PMID- 11507131
TI  - Recombinant human bone morphogenetic protein-2 accelerates healing in a rabbit
      ulnar osteotomy model.
AB  - BACKGROUND: Approximately 5% to 20% of fractures have delayed or impaired
      healing. Therefore, it is desirable to develop new therapies to enhance fracture
      healing that can be used in conjunction with traditional treatment methods. The
      purpose of this study was to evaluate the ability of a single application of
      recombinant human bone morphogenetic protein-2 to accelerate fracture-healing in
      a rabbit ulnar osteotomy that heals spontaneously. METHODS: Bilateral mid-ulnar
      osteotomies (approximately 0.5 to 1.0 mm wide) were created in seventy-two
      skeletally mature male rabbits. The limbs were assigned to one of three groups:
      those treated with an absorbable collagen sponge containing recombinant human
      bone morphogenetic protein-2, those treated with an absorbable collagen sponge
      containing buffer, and those left untreated. In the first two groups, an 8 20-mm
      strip of absorbable collagen sponge containing either 40 g of recombinant human
      bone morphogenetic protein-2 or buffer only was wrapped around the osteotomy
      site. The rabbits were killed at two, three, four, or six weeks after surgery. In
      addition, twenty-four age-matched rabbits were used to provide data on the
      properties of intact limbs. The retention of recombinant human bone morphogenetic
      protein-2 at the osteotomy site was determined with scintigraphic imaging of
      (125)I-labeled recombinant human bone morphogenetic protein-2. After the rabbits
      were killed, the limbs were scanned with peripheral quantitative computed
      tomography to assess the area and mineral content of the mineralized callus. The
      limbs were then tested to failure in torsion, and undecalcified specimens were
      evaluated histologically. RESULTS: Gamma scintigraphy of (125)I-recombinant human
      bone morphogenetic protein-2 showed that 73% +/- 6% (mean and standard deviation)
      of the administered dose was initially retained at the fracture site.
      Approximately 37% +/- 10% of the initial dose remained at the site one week after
      surgery, and 8% +/- 7% remained after two weeks. The mineralized callus area was
      similar in all groups at two weeks, but it was 20% to 60% greater in the ulnae
      treated with recombinant human bone morphogenetic protein-2 than in either the
      ulnae treated with buffer or the untreated ulnae at three, four, and six weeks (p
      < 0.05). Biomechanical properties were similar in all groups at two weeks, but
      they were at least 80% greater in the ulnae treated with recombinant human bone
      morphogenetic protein-2 at three and four weeks than in either the ulnae treated
      with buffer (p < 0.005) or the untreated ulnae (p < 0.01). By four weeks, the
      biomechanical properties of the ulnae treated with recombinant human bone
      morphogenetic protein-2 were equivalent to those of the intact ulnae, whereas the
      biomechanical properties of both the ulnae treated with buffer and the untreated
      ulnae had reached only approximately 45% of those of the intact ulnae. At six
      weeks, the biomechanical properties were similar in all groups and were
      equivalent to those of the intact ulnae. The callus geometry and biomechanical
      properties of the ulnae treated with buffer were equivalent to those of the
      untreated ulnae at all time-points. CONCLUSIONS AND CLINICAL RELEVANCE: These
      findings indicate that treatment with an absorbable collagen sponge containing
      recombinant human bone morphogenetic protein-2 enhances healing of a long-bone
      osteotomy that heals spontaneously. Specifically, osteotomies treated with
      recombinant human bone morphogenetic protein-2 healed 33% faster than osteotomies
      left untreated. The results of this study provide a rationale for testing the
      ability of recombinant human bone morphogenetic protein-2 to accelerate healing
      in patients with fractures requiring open surgical management.

PMID- 11507132
TI  - Posterior cruciate ligament-retaining total knee arthroplasty in patients with
      rheumatoid arthritis.
AB  - BACKGROUND: Although initial reports on posterior cruciate ligament-retaining
      total knee arthroplasty in patients with rheumatoid arthritis have been
      encouraging, a high rate of late instability necessitating revision has been
      reported recently. The purpose of the present prospective study was to analyze
      the results of posterior cruciate ligament-retaining total knee arthroplasty in
      patients with rheumatoid arthritis. METHODS: Seventy-two posterior cruciate
      ligament-retaining total knee arthroplasties in fifty-one patients with
      rheumatoid arthritis were studied prospectively. All procedures were performed
      with the Miller-Galante I prosthesis. Eighteen patients (twenty-four knees) died
      before the eight-year follow-up and one patient (two knees) was lost to follow
      up, leaving forty-six knees (thirty-two patients) for review. These forty-six
      knees were evaluated clinically (with particular attention to posterior
      instability) and radiographically at annual intervals for a mean of 10.5 years
      (range, eight to fourteen years). RESULTS: Forty-four (95%) of forty-six knees
      had a good or excellent result at a mean of 10.5 years. However, nine (13%) of
      the original seventy-two knees had revision of the implant, with six of the
      revisions performed because of failure of a metal-backed patellar component. The
      rate of survival at ten years was 93% 4% with femoral or tibial revision for any
      reason as the end point and 81% 5% with any reoperation as the end point. There
      was no aseptic loosening in any knee. Posterior instability was identified
      clinically and/or radiographically in two (2.8%) of the original seventy-two
      knees; both unstable knees were in the same patient. CONCLUSION: Posterior
      cruciate ligament-retaining total knee arthroplasty yielded satisfactory clinical
      and radiographic results in patients with rheumatoid arthritis at intermediate
      term follow-up (mean, 10.5 years). Therefore, we believe that it remains an
      excellent treatment option for these patients.

PMID- 11507133
TI  - Interactive magnetic resonance image-guided aspiration therapy of a glenoid
      labral cyst: a case report.

PMID- 11507135
TI  - From oranges and lemons to glucosamine and chondroitin sulfate: clinical
      observations stimulate basic research.

PMID- 11507136
TI  - Errors of language in orthopaedics.

PMID- 11507137
TI  - Who really first described and explained the suprascapular nerve entrapment
      syndrome?

PMID- 11507138
TI  - The usefulness of meta-analyses in treatment decisions.

PMID- 11507139
TI  - Operative versus functional treatment of ruptures of the lateral ankle ligaments.

PMID- 11507140
TI  - Prophylactic low-dose aspirin therapy in patients having hip-fracture surgery or
      elective arthroplasty.

PMID- 11507141
TI  - True wear rates as predictors of risk for osteolysis after total hip
      arthroplasty.

PMID- 11507142
TI  - Case-control studies and randomized clinical trials in evidence-based
      orthopaedics.

PMID- 11507143
TI  - Intramedullary nailing for the treatment of unicameral bone cysts.

PMID- 11507150
TI  - Glossary of terms for evidence-based orthopaedics.

PMID- 11507146
TI  - Tourniquet use during total knee arthroplasty did not reduce total blood loss.

PMID- 11507151
TI  - What's new in spine surgery.

PMID- 11507152
TI  - How muscles know how to adapt.

PMID- 11507153
TI  - Grandad, it ain't what you eat, it depends when you eat it--that's how muscles
      grow!

PMID- 11507155
TI  - Back-propagating action potentials mediate calcium signalling in dendrites of
      bitufted interneurons in layer 2/3 of rat somatosensory cortex.
AB  - 1. Bitufted interneurons in layer 2/3 of the rat (P14) somatosensory cortex have
      elongated apical and basal dendritic arbors that can span the entire depth of the
      cortex. Simultaneous dendritic and somatic whole-cell voltage recordings combined
      with Ca2+ fluorescence measurements were made to quantify voltage and Ca2+
      signalling in dendritic arbors of bitufted neurons. 2. Action potentials (APs)
      initiated close to the soma by brief current injection back-propagated into the
      apical and basal dendritic arbors and evoked a transient increase in volume
      averaged dendritic Ca2+ concentration (Delta[Ca(2+)](i)) of about 140 nM peak
      amplitude per AP. The AP evoked Ca2+ signal decayed with a time constant of about
      200 ms. 3. A relatively high endogenous Ca(2+) binding ratio of approximately 285
      determines the comparatively small rise in [Ca(2+)](i) of bitufted cell dendrites
      evoked by a back-propagating AP. 4. The [Ca(2+)](i) transient evoked by back
      propagating dendritic APs decreased with distance (< or = 50 microm) from the
      soma in some neurons. At distances greater than 50 microm transients did not show
      a spatial gradient between the proximal and distal dendritic branches. 5. During
      trains of APs the mean amplitude of the steady-state increase in dendritic
      [Ca(2+)](i) encoded the AP frequency linearly up to 40 Hz with a slope of 20 nM
      Hz(-1). 6. The results suggest that APs initiated in the axon of bitufted neurons
      back-propagate and 'copy' the pattern of the axon's electrical activity also to
      the dendritic arbor. The AP pattern is transduced into a transient rise of
      dendritic [Ca(2+)](i) which, presumably, can regulate the receptive properties of
      the dendritic arbor for synaptic input. 7. Bitufted interneurons in layer 2/3 of
      the rat (P14) somatosensory cortex have elongated apical and basal dendritic
      arbors that can span the entire depth of the cortex. Simultaneous dendritic and
      somatic whole-cell voltage recordings combined with Ca2+ fluorescence
      measurements were made to quantify voltage and Ca2+ signalling in dendritic
      arbors of bitufted neurons. 8. Action potentials (APs) initiated close to the
      soma by brief current injection back-propagated into the apical and basal
      dendritic arbors and evoked a transient increase in volume-averaged dendritic
      Ca2+ concentration (Delta[Ca(2+)](i)) of about 140 nM peak amplitude per AP. The
      AP evoked Ca2+ signal decayed with a time constant of about 200 ms. 9. A
      relatively high endogenous Ca2+ binding ratio of approximately 285 determines the
      comparatively small rise in [Ca(2+)](i) of bitufted cell dendrites evoked by a
      back-propagating AP. 10. The [Ca(2+)](i) transient evoked by back-propagating
      dendritic APs decreased with distance (< or = 50 microm) from the soma in some
      neurons. At distances greater than 50 microm transients did not show a spatial
      gradient between the proximal and distal dendritic branches. 11. During trains of
      APs the mean amplitude of the steady-state increase in dendritic [Ca(2+)](i)
      encoded the AP frequency linearly up to 40 Hz with a slope of 20 nM Hz(-1). 12.
      The results suggest that APs initiated in the axon of bitufted neurons back
      propagate and also 'copy' the pattern of the axon's electrical activity to the
      dendritic arbor. The AP pattern is transduced into a transient rise of dendritic
      [Ca(2+)](i) which, presumably, can regulate the receptive properties of the
      dendritic arbor for synaptic input.

PMID- 11507154
TI  - Control of IP(3)-mediated Ca2+ puffs in Xenopus laevis oocytes by the Ca2+
      binding protein parvalbumin.
AB  - 1. Elementary events of Ca2+ release (Ca2+ puffs) can be elicited from discrete
      clusters of inositol 1,4,5 trisphosphate receptors (IP(3)Rs) at low
      concentrations of IP(3). Ca(2+) puffs have rarely been observed unless elicited
      by either hormone treatment or introduction of IP(3) into the cell. However,
      cells appear to have sufficient concentrations of IP(3) (0.1-3.0 microM) to
      induce Ca2+ release under resting conditions. 2. Here, we investigated Ca2+ puff
      activity in non-stimulated Xenopus oocytes using confocal microscopy. The
      fluorescent Ca2+ dye indicators Calcium Green 1 and Oregon Green 488 BAPTA-2 were
      injected into oocytes to monitor basal Ca2+ activity. 3. In this preparation,
      injection or overexpression of parvalbumin, an EF-hand Ca(2+)-binding protein
      (CaBP), induced Ca2+ puffs in resting Xenopus oocytes. This activity was
      inhibited by heparin, an IP(3)R channel blocker, and by mutation of the Ca(2+)
      binding sites in parvalbumin. 4. Ca2+ puff activity was also evoked by injection
      of low concentrations of the Ca2+ chelator EGTA, but not by calbindin D(28k),
      another member of the EF-hand CaBP superfamily. 5. BAPTA and the Ca2+ indicator
      dye Oregon Green 488 BAPTA-1 evoked Ca2+ puff activity, while the dextran
      conjugate of Oregon Green 488 BAPTA-1 did not. These data indicate that a Ca(2+)
      buffer must be mobile in order to increase Ca2+ puff activity. 6. Together, the
      data indicate that some IP(3)Rs spontaneously release Ca2+ under resting
      concentrations of IP(3). These elementary Ca2+ events appear to be below the
      level of detection of current imaging techniques. We suggest that parvalbumin
      evokes Ca2+ puffs by coordinating the activity of elementary IP(3)R channel
      openings. 7. We conclude that Ca2+ release can be evoked not only by hormone
      induced increases in IP(3), but also by expression of mobile cytosolic CaBPs
      under resting concentrations of IP(3).

PMID- 11507156
TI  - Changes in extracellular Ca2+ can affect the pattern of discharge in rat thalamic
      neurons.
AB  - 1. The aim of this study was to investigate some of the cellular mechanisms
      involved in the effects caused by changes in extracellular Ca2+ concentration
      ([Ca2+](o)). 2. Current- and voltage-clamp experiments were carried out on
      acutely isolated thalamic neurons of rats. 3. Increasing [Ca2+](o) alone induced
      a transition of the discharge from single spike to burst mode in isolated current
      clamped neurons. 4. Increasing [Ca(2+)](o) caused the voltage-dependent
      characteristics of the low voltage-activated (LVA) transient Ca2+ currents to
      shift towards positive values on the voltage axis. Changing [Ca2+](o) from 0.5 to
      5 mM caused the inactivation curve to shift by 21 mV. 5. Extracellular Ca2+
      blocked a steady cationic current. This current reversed at -35 mV, was scarcely
      affected by Mg2+ and was completely blocked by the non-selective cation channel
      inhibitor gadolinium (10 microM). The effect of [Ca2+](o) was mimicked by 500
      microM spermine, a polyamine which acts as an agonist for the Ca(2+)-sensing
      receptor, and was modulated by intracellular GTP-gamma-S. 6. At the resting
      potential, both the voltage shift and the block of the inward current removed the
      inactivation of LVA calcium channels and, together with the increase in the Ca2+
      driving force, favoured a rise in the low threshold Ca2+ spikes, causing the
      thalamic firing to change to the oscillatory mode. 7. Our data indicate that
      [Ca2+](o) is involved in multiple mechanisms of control of the thalamic relay and
      pacemaker activity. These findings shed light on the correlation between
      hypercalcaemia, low frequency EEG activity and symptoms such as sleepiness and
      lethargy described in many clinical papers.

PMID- 11507157
TI  - Modulation of a voltage-gated calcium channel linked to activation of glutamate
      receptors and calcium-induced calcium release in the catfish retina.
AB  - 1. Catfish (Ictalurus punctatus) retinal cone horizontal cells contain an L-type
      calcium current that has been proposed to be involved in visual processing. Here
      we report on the modulation of this current by activation of glutamate receptors
      and calcium-induced calcium release (CICR) from intracellular calcium stores. 2.
      Fluorescence data obtained from isolated horizontal cells loaded with indo-1
      provided evidence of calcium release from an intracellular calcium store
      sensitive to caffeine, calcium and ryanodine. In the presence of caffeine,
      ryanodine-sensitive stores released calcium in a transient manner. Release of
      calcium was blocked when cells were preincubated in BAPTA, in the presence of
      ruthenium red, or in low concentrations of ryanodine. 3. The release of calcium
      from ryanodine-sensitive stores directly corresponded with a decrease of the
      voltage-gated L-type calcium current amplitude. Caffeine-induced modulation of
      the calcium current was reduced in the presence of ruthenium red. 4. Activation
      of ionotropic kainate receptors on catfish cone horizontal cells triggered CICR
      from ryanodine-sensitive stores and mimicked inhibition of the voltage-gated
      calcium current. Kainate-induced inhibition of the calcium current was diminished
      when intracellular calcium stores were inhibited with ruthenium red or depleted
      with ryanodine, or when calmodulin antagonists or CaM kinase II inhibitors were
      present. 5. These results provide evidence that activation of an ionotropic
      glutamate receptor on catfish cone horizontal cells is linked to calcium release
      from ryanodine-sensitive intracellular calcium stores and modulation of the L
      type calcium current activity. Inhibition of this calcium current directly or
      indirectly involves calmodulin and CaM kinase II and represents a possible
      mechanism used by horizontal cells to affect response properties of these cells.

PMID- 11507158
TI  - Kinetic analysis of open- and closed-state inactivation transitions in human
      Kv4.2 A-type potassium channels.
AB  - 1. We studied the gating kinetics of Kv4.2 channels, the molecular substrate of
      neuronal somatodendritic A-type currents. For this purpose wild-type and mutant
      channels were transiently expressed in the human embryonic kidney (HEK) 293 cell
      line and currents were measured in the whole-cell patch-clamp configuration. 2.
      Kv4.2 channels inactivated from pre-open closed state(s) with a mean time
      constant of 959 ms at -50 mV. This closed-state inactivation was not affected by
      a deletion of the Kv4.2 N-terminus (Delta2-40). 3. Kv4.2 currents at +40 mV
      inactivated with triple-exponential kinetics. A fast component (tau = 11 ms)
      accounted for 73 %, an intermediate component (tau = 50 ms) for 23 % and a slow
      component (tau = 668 ms) for 4 % of the total decay. 4. Both the fast and the
      intermediate components of inactivation were slowed by a deletion of the Kv4.2 N
      terminus (tau = 35 and 111 ms) and accounted for 33 and 56 %, respectively, of
      the total decay. The slow component was moderately accelerated by the truncation
      (tau = 346 ms) and accounted for 11 % of the total Kv4.2 current inactivation. 5.
      Recovery from open-state inactivation and recovery from closed-state inactivation
      occurred with similar kinetics in a strongly voltage-dependent manner. Neither
      recovery reaction was affected by the N-terminal truncation. 6. Kv4.2 Delta2-40
      channels displayed slowed deactivation kinetics, suggesting that the N-terminal
      truncation leads to a stabilization of the open state. 7. Simulations with an
      allosteric model of inactivation, supported by the experimental data, suggested
      that, in response to membrane depolarization, Kv4.2 channels accumulate in the
      closed-inactivated state(s), from which they directly recover, bypassing the open
      state.

PMID- 11507159
TI  - Temperature dependence of human muscle ClC-1 chloride channel.
AB  - 1. In the present work we investigated the dependence on temperature of the ionic
      conductance and gating of human muscle ClC-1 chloride channels, transiently
      expressed in human embryonic kidney (HEK 293) cells. 2. At normal pH, ClC-1
      currents deactivated at negative potentials with a double-exponential time
      course. The time constants of the exponential components, corresponding to the
      relaxations of the fast and slow gates, were temperature dependent with Q(10)
      values of approximately 3 and approximately 4, respectively. Current amplitude
      increased with increasing temperature with a Q(10) of approximately 1.6. 3. The
      voltage dependence of the two gating processes was shifted towards more positive
      potentials with increasing temperature. The half-saturation voltage (V(1/2)) of
      the steady-state open probability (P(o)) was shifted by approximately 23 and
      approximately 34 mV per 10 degrees C increase in temperature, for the fast and
      slow gate, respectively. 4. At low pH, the voltage dependence of ClC-1 was
      reversed and currents were activated by hyperpolarisation with a single
      exponential time course. This type of gating in ClC-1 resembled the slow gating
      of the Torpedo ClC-0 homologue, but differed with respect to its kinetics and
      temperature dependence, with a Q(10) of gating relaxations at negative potentials
      of approximately 5. The Arrhenius plot of ClC-1 conductance at low pH had a clear
      break point at approximately 25 degrees C, with higher Q(10) values at lower
      temperatures. 5. The temperature sensitivity of relaxation and open probability
      of the slow gate, which in both ClC-0 and ClC-1 controls two pores
      simultaneously, implies that the slow gating of ClC-1 is mechanistically
      different from that of ClC-0.

PMID- 11507160
TI  - A pH-sensitive chloride current in the chemoreceptor cell of rat carotid body.
AB  - 1. Cardiorespiratory response to acidosis is initiated by the carotid body. 2.
      The direct effect of extracellular pH (pH(o)) on the chloride currents of
      isolated chemoreceptor cells of the rat carotid body was investigated using the
      whole-cell patch-clamp technique. 3. On applying intra- and extracellular
      solutions with a symmetrical high-Cl(-) content and with the monovalent cations
      replaced with membrane-impermeant ones, an inwardly rectifying Cl(-) current was
      found. 4. The current activated slowly and did not display any time-dependent
      inactivation. Current activation was present at membrane potentials negative to 0
      mV (pH(o) = 7.0). 5. The current was activated by extracellular acidosis and
      inhibited by alkalosis in the physiologically relevant pH range of 7.0-7.8. 6.
      The current was reduced by 0.1 mM Cd2+ to the level of the leak current and by 1
      mM anthracene-9-carboxylic acid (9-AC) to about 40 %, while 0.1 mM Ba2+ had no
      effect. 7. Application of 1 mM 9-AC caused a slow but statistically significant
      increase in the resting pH(i) (from a mean of 7.29 to 7.37 in 5 min) in clusters
      of chemoreceptor cells in CO(2)/HCO3(-)-buffered media as measured with carboxy
      SNARF-1. 8. When membrane potential changes were estimated in the cell-attached
      mode, 1 mM 9-AC hyperpolarized three out of five tested cells (by 14 mV in
      average) incubated in CO(2)/HCO3(-)-buffered media. 9. In summary, chemoreceptor
      cells express an inwardly rectifying Cl(-) current, which is directly regulated
      by pH(o). The current may participate in intracellular acidification and membrane
      depolarization during acidic challenge.

PMID- 11507161
TI  - Rapid acid extrusion response triggered by alpha(1) adrenoceptor in CHO cells.
AB  - 1. Using a microphysiometer with synchronized valve switching, we investigated
      real-time acid extrusion from Chinese hamster ovary (CHO) cells in which human
      alpha(1) adrenoceptor (AR) is stably expressed, in response to noradrenaline
      (NA). 2. In the cells expressing alpha(1a) AR, the time course of extracellular
      acidification after stimulation had two phases; in the first phase it transiently
      reached a rate several times greater than the base rate with a peak at around 10
      s, and in the second it increased to 2 times the base rate and reached a plateau
      in 2 min. Both phases showed a concentration-dependent increase of acidification
      rate in response to NA, but had distinct pEC(50) values; 5.6 for the transient
      phase and 7.2 for the steady phase. 3. In the cells expressing alpha(1b) AR, the
      transient phase was not detected but the steady phase was observed. The pEC(50)
      value was 7.1, although the magnitude of the response was much smaller than that
      with alpha(1a) AR. 4. Both 5-(N-ethyl-N-isopropyl)amiloride (EIPA) and HOE642
      inhibited the acid extrusion response by either AR in a concentration-dependent
      manner. EIPA and HOE642 had high pIC(50) values (7.4 and 7.3, respectively) for
      inhibition of the transient phase response via alpha(1a) AR. In the inhibition of
      the steady phase response via alpha(1a) AR, both drugs revealed the presence of
      two components in the response; one had high pIC(50) values (8.1 and 8.2 for EIPA
      and HOE642, respectively) and the other had low pIC(50) values (5.6 and 6.0,
      respectively). In contrast, the steady phase response via alpha(1b) AR was
      inhibited by EIPA and HOE642 with low pIC(50) values (5.3 and 5.9, respectively).
      5. As Ca2+ was depleted, the alpha(1a) AR-induced transient phase disappeared,
      while the steady phase was not affected. 6. These results suggest that alpha(1a)
      AR drives two acid extrusion systems in CHO cells upon stimulation; one elicits
      the transient response, which is largely mediated by an EIPA/HOE642-sensitive and
      Ca(2+)-dependent Na(+)-H(+) exchanger (NHE), presumably NHE1, and the other
      induces the steady acid extrusion that is mediated by NHE1 and another NHE which
      has low sensitivity to both EIPA and HOE642. alpha(1b) AR drives only the steady
      phase acid extrusion response, which is mainly mediated by NHEs other than NHE1.

PMID- 11507162
TI  - Fast synaptic transmission mediated by P2X receptors in CA3 pyramidal cells of
      rat hippocampal slice cultures.
AB  - 1. A fast ATP-mediated synaptic current was identified in CA3 pyramidal cells in
      organotypic hippocampal slice cultures. In the presence of inhibitors for
      ionotropic glutamate and GABA receptors, extracellular stimulation in the
      pyramidal cell layer evoked fast synaptic currents that reversed near 0 mV,
      reflecting an increase in a non-selective cationic conductance. This response was
      mimicked by focal application of ATP. Antagonists of ionotropic P2X receptors
      reduced both synaptic and ATP-induced currents. 2. Using a pharmacological
      approach, the source of synaptically released ATP was determined. Synaptic ATP
      responses were insensitive to presynaptic blockade of GABAergic transmission
      between interneurons and CA3 pyramidal cells with the mu-opioid receptor agonist
      D-Ala(2),MePhe(4),Met(O)(5)-ol-enkephalin (FK33-824), but were blocked by
      adenosine, which inhibits glutamate release from synaptic terminals in the
      hippocampus. However, selective inhibition of mossy fibre glutamatergic
      transmission with the metabotropic glutamate receptor group II agonist
      (2S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine (DCG IV) did not affect the
      response. This result points to the associational fibres as the source of the ATP
      mediated synaptic response. 3. These results suggest that ATP, coreleased with
      glutamate, induces a synaptic response in CA3 pyramidal cells that is observed
      mainly under conditions of synchronous discharge from multiple presynaptic
      inputs.

PMID- 11507163
TI  - Mixed excitatory and inhibitory GABA-mediated transmission in chick cochlear
      nucleus.
AB  - 1. Neurons of the chick nucleus magnocellularis (NM) receive depolarizing
      GABAergic input from the superior olivary nucleus (SON). We examined the response
      to exogenous GABA or to stimulation of GABAergic fibres in order to identify the
      ionic basis of GABAergic synaptic transmission and its physiological
      implications. 2. Reversal potentials of GABA responses (E(GABA)) were determined
      exclusively by the Cl(-) gradient, measured using whole-cell recording. With
      gramicidin-perforated patch recording, E(GABA) was -25 +/- 5 mV (mean +/- S.D.),
      and was stable between embryonic day 17 and post-hatch day 10. With normal
      intracellular Cl(-), GABA depolarized neurons by 12 mV. 3. In current clamp,
      repetitive activation of the GABAergic axons reduced the probability of spiking
      in response to simultaneous stimulation of excitatory axons. However, IPSPs could
      themselves elicit action potentials, and facilitation of IPSPs by repetitive
      activation could lead to a characteristic pattern of spiking. 4. These data
      indicate that IPSPs with reversal potentials positive to spike threshold may have
      dual functions, depending on the context of their activation.

PMID- 11507164
TI  - Interaction between the RGS domain of RGS4 with G protein alpha subunits mediates
      the voltage-dependent relaxation of the G protein-gated potassium channel.
AB  - 1. In native cardiac myocytes, there is a time dependence to the G protein-gated
      inwardly rectifying K(+) (K(G)) channel current during voltage steps that
      accelerates as the concentration of acetylcholine is increased. This phenomenon
      has been called 'relaxation' and is not reproduced in the reconstituted
      Kir3.1/Kir3.4 channel in Xenopus oocytes. We have shown that RGS4, a regulator of
      G protein signalling, restores relaxation to the reconstituted Kir3.1/Kir3.4
      channel. In this study, we examined the mechanism of this phenomenon by
      expressing various combinations of membrane receptors, G proteins, Kir3.0
      subunits and mutants of RGS4 in Xenopus oocytes. 2. RGS4 restored relaxation to
      K(G) channels activated by the pertussis toxin (PTX)-sensitive G protein-coupled
      m(2)-muscarinic receptor but not to those activated by the G(s) protein-coupled
      beta(2)-adrenergic receptor. 3. RGS4 induced relaxation not only in heteromeric
      K(G) channels composed of Kir3.1 and Kir3.4 but also in homomeric assemblies of
      either an active mutant of Kir3.1 (Kir3.1/F137S) or an isoform of Kir3.2
      (Kir3.2d). 4. Truncation mutants of RGS4 showed that the RGS domain itself was
      essential to reproduce the effect of wild-type RGS4 on the K(G) channel. 5. The
      mutation of residues in the RGS domain which interact with the alpha subunit of
      the G protein (G(alpha)) impaired the effect of RGS4. 6. This study therefore
      shows that interaction between the RGS domain and PTX-sensitive G(alpha) subunits
      mediates the effect of RGS4 on the agonist concentration-dependent relaxation of
      K(G) channels.

PMID- 11507165
TI  - Recombinant GABA(C) receptors expressed in rat hippocampal neurons after
      infection with an adenovirus containing the human rho1 subunit.
AB  - 1. A recombinant adenovirus was generated with the human rho1 GABA(C) receptor
      subunit (adeno-rho). Patch-clamp and antibody staining were employed to confirm
      functional expression of recombinant rho1 receptors after infection of human
      embryonic kidney cells (HEK293 cell line), human embryonic retinal cells (911
      cell line), dissociated rat hippocampal neurons and cultured rat hippocampal
      slices. 2. Standard whole-cell recording and Western blot analysis using rho1
      GABA(C) receptor antibodies revealed that recombinant rho1 receptors were
      expressed in HEK293 and 911 cells after adeno-rho infection and exhibited
      properties similar to those of rho1 receptors after standard transfection. 3.
      Cultured rat hippocampal neurons (postnatal day (P)3-P5) did not show a native
      GABA(C)-like current. After adeno-rho infection, however, a GABA(C)-like current
      appeared in 70-90 % of the neurons. 4. Five days after infection, expression of
      GABA(C) receptors in hippocampal neurons significantly decreased native GABA(A)
      receptor currents from 1200 +/- 300 to 150 +/- 70 pA (n = 10). The native
      glutamate-activated current was unchanged. 5. Hippocampal slices (P8) did not
      show a native GABA(C)-like current, although recombinant rho1 receptors could be
      expressed in cultured hippocampal slices after adeno-rho infection. 6. These data
      indicate that an adenovirus can be used to express recombinant GABA(C) receptors
      in hippocampal neurons. This finding could represent an important step towards
      the gene therapy of CNS receptor-related diseases.

PMID- 11507166
TI  - Effects of concentric and eccentric contractions on phosphorylation of
      MAPK(erk1/2) and MAPK(p38) in isolated rat skeletal muscle.
AB  - 1. Exercise and contractions of isolated skeletal muscle induce phosphorylation
      of mitogen-activated protein kinases (MAPKs) by undefined mechanisms. The aim of
      the present study was to determine exercise-related triggering factors for the
      increased phosphorylation of MAPKs in isolated rat extensor digitorum longus
      (EDL) muscle. 2. Concentric or eccentric contractions, or mild or severe passive
      stretches were used to discriminate between effects of metabolic/ionic and
      mechanical alterations on phosphorylation of two MAPKs: extracellular signal
      regulated kinase 1 and 2 (MAPK(erk1/2)) and stress-activated protein kinase p38
      (MAPK(p38)). 3. Concentric contractions induced a 5-fold increase in MAPK(erk1/2)
      phosphorylation. Application of the antioxidants N-acetylcysteine (20 mM) or
      dithiothreitol (5 mM) suppressed concentric contraction-induced increase in
      MAPK(erk1/2) phosphorylation. Mild passive stretches of the muscle increased
      MAPK(erk1/2) phosphorylation by 1.8-fold, whereas the combination of acidosis and
      passive stretches resulted in a 2.8-fold increase. Neither concentric
      contractions, nor mild stretches nor acidosis significantly affected
      phosphorylation of MAPK(p38). 4. High force applied upon muscle by means of
      either eccentric contractions or severe passive stretches resulted in 5.7- and
      9.5-fold increases of phosphorylated MAPK(erk1/2), respectively, whereas
      phosphorylation of MAPK(p38) increased by 7.6- and 1.9-fold (not significant),
      respectively. 5. We conclude that in isolated rat skeletal muscle an increase in
      phosphorylation of both MAPK(erk1/2) and MAPK(p38) is induced by mechanical
      alterations, whereas contraction-related metabolic/ionic changes (reactive oxygen
      species and acidosis) cause increased phosphorylation of MAPK(erk1/2) only. Thus,
      contraction-induced phosphorylation can be explained by the combined action of
      increased production of reactive oxygen species, acidification and mechanical
      perturbations for MAPK(erk1/2) and by high mechanical stress for MAPK(p38).

PMID- 11507167
TI  - Generation of slow waves in the antral region of guinea-pig stomach--a stochastic
      process.
AB  - 1. Slow waves were recorded from the circular muscle layer of the antral region
      of guinea-pig stomach. Slow waves were abolished by 2APB, an inhibitor of IP(3)
      induced Ca2+ release. 2. When the rate of generation of slow waves was monitored
      it was found to vary from cycle to cycle around a mean value. The variation
      persisted after abolishing neuronal activity with tetrodotoxin. 3. When
      simultaneous recordings were made from interstitial cells in the myenteric region
      (ICC(MY)) and smooth muscle cells of the circular layer, variations in the rate
      of generation of slow waves were found to be linked with variations in the rate
      of generation of driving potentials by ICC(MY). 4. A preparation was devised
      which consisted of the longitudinal muscle layer and ICC(MY). In this preparation
      ICC(MY) and smooth muscle cells lying in the longitudinal muscle layer generated
      driving potentials and follower potentials, synchronously. 5. Driving potentials
      had two components, a rapid primary component that was followed by a prolonged
      plateau component. Caffeine (3 mM) abolished the plateau component; conversely
      reducing the external concentration of calcium ions [Ca2+](o) mainly affected the
      primary component. 6. Analysis of the variations in the rate of generation of
      driving potentials indicated that this arose because both the duration of
      individual driving potentials and the interval between successive driving
      potentials varied. 7. It is suggested that the initiation of pacemaker activity
      in a network of ICC(MY) is a stochastic process, with the probability of
      initiating a driving potential slowly increasing, after a delay, from a low to a
      higher value following the previous driving potential.

PMID- 11507168
TI  - Intercellular electrical communication among smooth muscle and endothelial cells
      in guinea-pig mesenteric arterioles.
AB  - 1. Current clamp studies using two patch electrodes and morphological
      observations have been performed in guinea-pig mesenteric arterioles to evaluate
      intercellular electrical couplings. 2. In electron micrographs, preparations were
      found to have a single layer of smooth muscle cells. Typical gap junctions were
      readily observed between endothelial cells only. 3. While immunoreactivity to
      connexin 40 was strongly expressed on the membranes of endothelial cells only,
      that to connexin 43 was expressed on both smooth muscle and endothelial cell
      membranes. 4. Neurobiotin injected into a smooth muscle cell diffused into
      several neighbouring smooth muscle cells while that injected into an endothelial
      cell diffused into many endothelial cells. 5. Acetylcholine-induced
      hyperpolarizations were conducted from endothelial cells to smooth muscle cells
      with a relative amplitude of 80.1 %. Ba(2+)-induced action potentials were
      conducted in the opposite direction with a relative amplitude of 92.4 %. 6. An
      electrotonic potential produced in a smooth muscle cell by current injection
      diminished steeply with distance as it spread along the muscle layer, plateauing
      at distances beyond 25 microm. An electrotonic potential produced in an
      endothelial cell spread within the intima with virtually no reduction.
      Electrotonic potentials could conduct through myoendothelial couplings, which
      seemed to behave as ohmic resistors without rectification. 7. The coupling
      resistance between adjacent smooth muscle cells was estimated to be at least 90
      MOhms and that between a smooth muscle cell and the whole endothelial layer to be
      0.9 GOhms. 8. The results indicate that although the resistance of myoendothelial
      couplings is appreciable, the endothelium may be important as a low resistance
      path connecting many smooth muscle cells.

PMID- 11507169
TI  - Aldosterone mediates the changes in hexose transport induced by low sodium intake
      in chicken distal intestine.
AB  - 1. In chickens, low Na+ diets markedly decrease the hexose transport in the
      rectal segment of the large intestine; transport in the ileum shows a lower, but
      significant reduction and transport in the jejunum is unaffected. These effects
      involve both apical (SGLT1) and basolateral (GLUT2) hexose transporters. 2. The
      role of the renin-angiotensin-aldosterone axis (RAAS) in the epithelial response
      to Na+ intake was studied in chickens fed high-NaCl (HS) and low-NaCl (LS) diets.
      The V(max) of alpha-methyl-D-glucoside and D-glucose were determined in vesicles
      from the brush-border (BBMVs) and basolateral (BLMVs) membranes, respectively.
      The binding of phlorizin to BBMV and cytochalasin B to BLMV were used as
      indicators of the abundance of SGLT1 and GLUT2, respectively. 3. In HS-adapted
      chickens, the serum concentration of aldosterone (means +/- S.E.M.) was 35 +/- 5
      pg ml(-1) (n = 6) and that of renin was 20 +/- 2 ng ml(-1) (n = 3). In LS-fed
      birds, these values were 166 +/- 12 pg ml(-1) (n = 6) and 122 +/- 5 ng ml(-1) (n
      = 3), respectively. Administration of captopril, the inhibitor of the angiotensin
      converting enzyme (ACE), to LS-chickens lowered the aldosterone serum
      concentration without affecting the renin concentration. Captopril also prevented
      the reduction of apical and basolateral hexose transport in ileum and rectum
      characteristic of the intestinal response to LS adaptation. 4. Administration of
      the aldosterone antagonist spironolactone to LS-adapted chickens did not affect
      the serum concentrations of aldosterone, but prevented the effects of LS intake
      on hexose transport in both apical and basolateral membranes. This suggests that
      the effects of aldosterone are mediated by cytosolic mineralcorticoid receptors.
      5. Administration of exogenous aldosterone to HS-fed birds induced hexose
      transport and binding properties typical of the LS-adapted animals. These
      findings support the view that aldosterone, besides its primary role in
      controlling intestinal Na+ absorption, can also modulate the expression of apical
      and basolateral glucose transporters in the chicken distal intestine.

PMID- 11507170
TI  - Tryptophan degradation by human placental indoleamine 2,3-dioxygenase regulates
      lymphocyte proliferation.
AB  - 1. The physiological importance of human placental indoleamine 2,3-dioxygenase
      (EC 1.13.11.42), the first and rate-limiting enzyme in tryptophan metabolism, in
      regulating feto-maternal immunology has been studied. 2. Concentrations were
      measured in placental villous explant conditioned media of 14 amino acids that
      are known to be required for lymphocyte proliferation. In the absence of
      interferon-gamma only tryptophan and threonine were significantly lowered; in the
      presence of interferon-gamma (known to stimulate indoleamine 2,3-dioxygenase)
      tryptophan but not threonine depletion was much greater. 3. Peripheral blood
      mononuclear cell proliferation determined by measuring thymidine incorporation
      into DNA following culture in the medium previously conditioned by culture of
      villous explants was markedly reduced when placental indoleamine 2,3-dioxygenase
      was stimulated with interferon-gamma. Inhibition of placental indoleamine 2,3
      dioxygenase by 1-methyl-tryptophan prevented inhibition of thymidine
      incorporation. Supplementation of the conditioned medium with tryptophan but no
      other amino acid completely reversed the inhibition of thymidine incorporation.
      4. Flow cytometric analysis showed that CD4-positive T lymphocyte division was
      specifically suppressed by indoleamine 2,3-dioxygenase-mediated tryptophan
      depletion. This inhibition of T cell proliferation was due to arrest of cell
      cycle progression. 5. To study the mechanism of tryptophan sensing we examined
      the ability of 11 L-tryptophan analogues to support lymphocyte proliferation.
      Only L-tryptophan methyl and ethyl esters were able to stimulate proliferation in
      tryptophan-free media. Since both of these molecules are readily degraded to
      tryptophan by intracellular esterases this suggests that the tryptophan sensor is
      intracellular. 6. Our results show that mechanisms are present in the human
      placenta which are able to regulate cellular proliferation of the maternal immune
      system. This mechanism is dependent both on placental indoleamine 2,3-dioxygenase
      mediated tryptophan degradation and on tryptophan sensing systems within
      lymphocytes.

PMID- 11507171
TI  - A novel method for controlled and reversible long term compression of the
      umbilical cord in fetal sheep.
AB  - 1. In fetal sheep during late gestation the aims of the present study were to (1)
      develop a technique for inducing prolonged but reversible periods of controlled
      compression of the umbilical cord and (2) characterise the cardiovascular,
      endocrine and metabolic responses to this challenge. 2. Under 1-2 % halothane
      anaesthesia, 16 Welsh Mountain sheep fetuses were chronically instrumented at 118
      +/- 2 days of gestation (term is ca 145 days) with an inflatable occluder cuff
      around the umbilical cord, amniotic and femoral vascular catheters and with
      transit-time flow probes around the contra-lateral femoral artery and an
      umbilical artery. At 125 days, umbilical blood flow was reduced by 30 % from a
      pre-determined 24 h baseline for 3 days by automated servo-controlled inflation
      of the occluder cuff (n = 8). The occluder was then deflated allowing return of
      umbilical blood flow to baseline. The remaining eight fetuses were used as sham
      operated controls in which the occluder was not inflated throughout the protocol.
      Fetal cardiovascular variables were recorded at 8 s intervals and arterial blood
      samples taken for measurement of blood gases, glucose and lactate and plasma
      adrenaline, noradrenaline and vasopressin concentration throughout the study. 3.
      Automated servo-controlled inflation of the occluder cuff, programmed to reduce
      umbilical blood flow by 30 % from baseline, reduced umbilical blood flow by 30.2
      +/- 1.7 %, with a coefficient of variation during compression of 6.5 +/- 1.1 %.
      Sustained partial compression of the umbilical cord produced falls in fetal
      arterial pH, P(a,O2), percentage O(2) saturation of haemoglobin, and hindlimb
      oxygen delivery, and increases in P(a,CO2), haemoglobin concentration, arterial
      blood oxygen carrying capacity and in blood glucose and lactate concentrations.
      While the reductions in P(a,O2), percentage saturation of haemoglobin and
      hindlimb oxygen delivery and the increase in P(a,CO2) were sustained throughout
      compression, the reduction in arterial pH and the increase in arterial oxygen
      carrying capacity had returned towards baseline values by 48 h compression. Fetal
      blood lactate concentrations reached a peak at 8 h of compression and,
      thereafter, were maintained at an elevated level relative to baseline. 4. Partial
      compression of the umbilical cord produced fetal hypertension, a reduction in
      femoral blood flow and, consequently, an increase in calculated fetal femoral
      vascular resistance for the duration of the challenge. In addition, the fall in
      heart rate measured in sham control fetuses by the end of the study, did not
      occur in cord-compressed fetuses. Cosinor analysis on 24 h rhythms of
      cardiovascular data indicated a significant increase in the amplitude of the 24 h
      rhythm in heart rate in cord-compressed fetuses relative to sham controls during
      the period of compression or sham-compression. Furthermore, cord compression led
      to an increase in fetal plasma noradrenaline, but not adrenaline and vasopressin
      concentrations relative to sham control fetuses. 5. In conclusion, a novel
      reversible method for controlled, long-term compression of the umbilical cord in
      sheep has been developed. The data show that sustained, partial compression of
      the umbilical cord produced moderate but sustained asphyxia, which resolved after
      the end of the compression period, and induced changes in fetal cardiovascular,
      endocrine and metabolic functions.

PMID- 11507172
TI  - Left ventricular stroke volume in the fetal sheep is limited by extracardiac
      constraint and arterial pressure.
AB  - 1. Extracardiac constraint and sensitivity to arterial pressure may be critical
      factors that limit the functional reserves of the developing fetal heart in
      utero. We hypothesise that extracardiac constraint is the predominant factor that
      limits fetal stroke volume (SV). To test this hypothesis we studied six
      chronically instrumented fetal sheep to determine the relative roles that
      extracardiac constraint and arterial pressure play in determining left
      ventricular (LV) function. 2. Pregnant ewes (128-131 days gestation, term = 147
      days) were anaesthetised (5 mg kg(-1) Propofol I.V., then 1.5 % halothane, 50 %
      O(2), balance N(2)O by inhalation) and instrumented using sterile surgical
      techniques to record LV end-diastolic pressure (P(lved)), aortic pressure
      (P(ao)), pericardial pressure (P(per)), and LV SV. 3. After a minimum of 72 h
      recovery, LV function was assessed by altering fetal blood volume to vary
      P(lved). Ventricular function curves were generated using two measures of
      ventricular function, SV and stroke work index (SWI = SV x P(ao)), and two
      measures of ventricular filling, P(lved) and LV end-diastolic transmural pressure
      (P(lved,tm) = P(lved) - P(per)). 4. Although decreasing P(lved) from the resting
      level decreased SV, increasing P(lved) from the resting level did not increase SV
      because the ventricular function curve plateaued. This plateau was not explained
      solely by an increase in aortic pressure, as the plateau remained present in the
      SWI versus P(lved) curve. When extracardiac constraint was accounted for (SV
      against P(lved,tm)), the plateau was largely eliminated (approximately 80 %). The
      remaining portion of the plateau (approximately 20 %) was eliminated when both
      extracardiac constraint and arterial pressure were accounted for (SWI versus
      P(lved,tm)). 5. Thus, the major limitation upon LV function in the near-term
      fetus results from extracardiac constraint limiting ventricular filling while, at
      the same time, a much smaller limitation arises from increasing arterial
      pressure.

PMID- 11507173
TI  - Effects of locomotor training on hindlimb regeneration in the urodele amphibian
      Pleurodeles waltlii.
AB  - 1. The effects of locomotor training on hindlimb regeneration were studied in the
      urodele amphibian Pleurodeles waltlii. 2. After amputation of one hindlimb at mid
      femur, adult animals were subjected to regular training sessions (1 h daily, 5
      days a week, over 8 months) of terrestrial stepping. 3. Eight months post
      amputation, trained animals exhibited regenerated limbs of reduced size as
      compared to animals kept in their aquaria. Histological data showed an abnormal
      regeneration of both the femur and distal structures (e.g. digit muscles,
      metatarsi and phalanges) while medial structures (e.g. tibia and fibula) were
      totally re-formed. The study of the electromyographical activity in regenerated
      limbs during stepping and that of their reflex responsiveness to electrical
      stimulation showed that both motor and sensory innervations were functional in
      the limb stump of trained animals. 4. The regenerative capacity of the abnormal
      stumps was preserved since following a second amputation a quite normal hindlimb
      was regenerated in 3 months, provided the re-amputated animals were not trained
      to terrestrial stepping. 5. The stress due to handling, change in locomotor
      medium (aquatic vs. terrestrial) and the friction of the wound epidermis with the
      ground were not involved in the disruption of limb regeneration. 6. The locomotor
      pattern, the reflex responsiveness and the muscle fibre composition were similar
      in supernumerary forelimbs grafted on the back and in normal forelimbs. However,
      the supernumerary forelimbs regenerated normally even in animals subjected to
      locomotor training while the hindlimb did not. It is concluded that the
      disrupting effects of locomotor training on limb regeneration were localized to
      the the limb directly involved in locomotion. 7. The mechanisms underlying
      abnormal limb regeneration in animals subjected to locomotor training are
      discussed.

PMID- 11507174
TI  - Thin fibre territories of nerves innervating hairs in the human forearm estimated
      from axon reflex vasodilatations.
AB  - 1. To study the territories of thin nerve fibres innervating hair follicles, we
      extracted single hairs from forearm skin. Scanning laser Doppler methodology was
      used to measure the evoked local increase of skin perfusion, the underlying
      assumption being that axon reflex vasodilatation would be evoked within the
      territory of extraction-activated thin nerve fibres. Ninety-two single hairs were
      extracted in 14 healthy males. 2. In 93 % of the cases perfusion increased
      transiently near the site of the extracted hair. No responses occurred when arm
      blood flow was occluded. In support of an underlying axon reflex mechanism the
      intensity of hair extraction-evoked pain correlated with the peak area of the
      response. In addition, after pre-extraction local anaesthesia, response
      components were seen in only 50 % of the cases and when they occurred they were
      very small. 3. The response had two components which could occur independently of
      each other. An early short-lasting component consisted of one or several separate
      areas with a peak total extension of 176 +/- 176 mm(2) (mean +/- S.D.), a peak
      maximal intensity (in percentage of pre-extraction perfusion) of 484 +/- 272 %,
      and a duration of 6-8 min. A later long-lasting component consisted of a single
      area of 51 +/- 107 mm(2), an intensity of 342 +/- 301 % and a duration of up to
      approximately 60 min. Perfusion could be influenced from a single hair in an
      asymmetrical skin area with diameters at right angles of 23 +/- 9 and 16 +/- 9
      mm, respectively. 4. We suggest that the responses were evoked by two sets of
      thin nerve fibres, one at a superficial level with fairly large innervation
      territories, and the other located more deeply close to the hair follicle and
      with smaller innervation territories.

PMID- 11507175
TI  - An action spectrum for melatonin suppression: evidence for a novel non-rod, non
      cone photoreceptor system in humans.
AB  - 1. Non-image forming, irradiance-dependent responses mediated by the human eye
      include synchronisation of the circadian axis and suppression of pineal melatonin
      production. The retinal photopigment(s) transducing these light responses in
      humans have not been characterised. 2. Using the ability of light to suppress
      nocturnal melatonin production, we aimed to investigate its spectral sensitivity
      and produce an action spectrum. Melatonin suppression was quantified in 22
      volunteers in 215 light exposure trials using monochromatic light (30 min pulse
      administered at circadian time (CT) 16-18) of different wavelengths (lambda(max)
      424, 456, 472, 496, 520 and 548 nm) and irradiances (0.7-65.0 microW cm(-2)). 3.
      At each wavelength, suppression of plasma melatonin increased with increasing
      irradiance. Irradiance-response curves (IRCs) were fitted and the generated half
      maximal responses (IR(50)) were corrected for lens filtering and used to
      construct an action spectrum. 4. The resulting action spectrum showed unique
      short-wavelength sensitivity very different from the classical scotopic and
      photopic visual systems. The lack of fit (r(2) < 0.1) of our action spectrum with
      the published rod and cone absorption spectra precluded these photoreceptors from
      having a major role. Cryptochromes 1 and 2 also had a poor fit to the data.
      Fitting a series of Dartnall nomograms generated for rhodopsin-based
      photopigments over the lambda(max) range 420-480 nm showed that rhodopsin
      templates between lambda(max) 457 and 462 nm fitted the data well (r(2) > or
      =0.73). Of these, the best fit was to the rhodopsin template with lambda(max) 459
      nm (r(2) = 0.74). 5. Our data strongly support a primary role for a novel short
      wavelength photopigment in light-induced melatonin suppression and provide the
      first direct evidence of a non-rod, non-cone photoreceptive system in humans.

PMID- 11507176
TI  - Effect of hypoxia on the hypopnoeic and apnoeic threshold for CO(2) in sleeping
      humans.
AB  - 1. Rhythmic breathing during sleep requires that P(CO2) be maintained above a
      sensitive hypocapnic apnoeic threshold. Hypoxia causes periodic breathing during
      sleep that can be prevented or eliminated with supplemental CO(2). The purpose of
      this study was to determine the effect of hypoxia in changing the difference
      between the eupnoeic P(CO2) and the P(CO2) required to produce hypopnoea or
      apnoea (hypopnoea/apnoeic threshold) in sleeping humans. 2. The effect of hypoxia
      on eupnoeic end-tidal partial pressure of CO(2) (P(ET,CO2)) and hypopnoea/apnoeic
      threshold P(ET,CO2) was examined in seven healthy, sleeping human subjects. A
      bilevel pressure support ventilator in a spontaneous mode was used to reduce
      P(ET,CO2) in small decrements by increasing the inspiratory pressure level by 2
      cmH2O every 2 min until hypopnoea (failure to trigger the ventilator) or apnoea
      (no breathing effort) occurred. Multiple trials were performed during both
      normoxia and hypoxia (arterial O(2) saturation, S(a,O2) = 80 %) in a random
      order. The hypopnoea/apnoeic threshold was determined by averaging P(ET,CO2) of
      the last three breaths prior to each hypopnoea or apnoea. 3. Hypopnoeas and
      apnoeas were induced in all subjects during both normoxia and hypoxia. Hypoxia
      reduced the eupnoeic P(ET,CO2) compared to normoxia (42.4 +/- 1.3 vs. 45.0 +/-
      1.1 mmHg, P < 0.001). However, no change was observed in either the hypopnoeic
      threshold P(ET,CO2) (42.1 +/- 1.4 vs. 43.0 +/- 1.2 mmHg, P > 0.05) or the apnoeic
      threshold P(ET,CO2) (41.3 +/- 1.2 vs. 41.6 +/- 1.0 mmHg, P > 0.05). Thus, the
      difference in P(ET,CO2) between the eupnoeic and threshold levels was much
      smaller during hypoxia than during normoxia (-0.2 +/- 0.2 vs. -2.0 +/- 0.3 mmHg,
      P < 0.01 for the hypopnoea threshold and -1.1 +/- 0.2 vs. -3.4 +/- 0.3 mmHg, P <
      0.01 for the apnoeic threshold). We concluded that hypoxia causes a narrowing of
      the difference between the baseline P(ET,CO2) and the hypopnoea/apnoeic threshold
      P(ET,CO2), which could increase the likelihood of ventilatory instability.

PMID- 11507177
TI  - Human motor control consequences of thixotropic changes in muscular short-range
      stiffness.
AB  - 1. The primary aim of the present study was to explore whether in healthy
      subjects the muscle contractions required for unrestrained voluntary wrist
      dorsiflexions are adjusted in strength to thixotropy-dependent variations in the
      short-range stiffness encountered in measurements of passive torque resistance to
      imposed wrist dorsiflexions. 2. After a period of rest, only the first movement
      in a series of passive wrist dorsiflexions of moderate amplitude exhibited clear
      signs of short-range stiffness in the torque response. During analogous types of
      voluntary movements, the extensor EMG during the first movement after rest showed
      a steep initial rise of activity, which apparently served to compensate for the
      short-range stiffness. 3. The passive torque resistance to minute repetitive
      wrist dorsiflexions (within the range of short-range stiffness) was markedly
      reduced after various types of mechanical agitation. During analogous low
      amplitude voluntary wrist dorsiflexions the extensor EMG signals were weaker
      after than before agitation. 4. Mechanical agitation also led to enhancement of
      passive dorsiflexion movements induced by weak constant torque pulses. In an
      analogous way, the movement-generating capacity of weak voluntary extensor
      activations (as determined by EMG recordings) was greatly enhanced by mechanical
      agitation. 5. The signals from a force transducer probe pressed against the wrist
      flexor tendons--during passive wrist dorsiflexions--revealed short-range
      stiffness responses which highly resembled those observed in the torque
      measurements, suggesting that the latter to a large extent emanated from the
      stretched, relaxed flexor muscles. During repetitive stereotyped voluntary wrist
      dorsiflexions, a close correspondence was observed between the degree of short
      range stiffness as sensed by the wrist flexor tension transducer and the strength
      of the initial extensor activation required for movement generation. 6. The
      results provide evidence that the central nervous system in its control of
      voluntary movements takes account of and compensates for the history-dependent
      degree of inherent short-range stiffness of the muscles antagonistic to the prime
      movers.

PMID- 11507178
TI  - Startle response of human neck muscles sculpted by readiness to perform ballistic
      head movements.
AB  - 1. An acoustic startle stimulus delivered in place of a 'go' signal in a
      voluntary reaction time (RT) task has been shown previously to advance the onset
      latency of a prepared distal limb movement without affecting the amplitude of the
      muscle response or movement kinematics. The primary goal of this study was to use
      muscles with a larger startle response to investigate whether the startling
      stimulus only triggered the RT movement or whether some form of interaction
      occurred between a startle response and a temporally advanced RT movement. 2.
      Twenty healthy male or female subjects were instructed to react as quickly as
      possible to an acoustic 'go' stimulus by performing a ballistic head flexion or
      right axial rotation. The 'go' stimulus was periodically replaced by an acoustic
      stimulus capable of eliciting a startle reflex. Separate startle-inducing stimuli
      under relaxed conditions before and after the movement trials served as control
      trials (CT trials). Bilateral surface electromyography of the orbicularis oculi,
      masseter, sternocleidomastoid and cervical paraspinal muscles, and head-mounted
      transducers were used to measure the muscle response and movement kinematics. 3.
      Muscle activation times in startled movement trials (ST trials) were about half
      those observed in RT trials, and were not significantly different from those
      observed in the startle CT trials. The duration of head acceleration was longer
      in ST trials than in RT trials and the amplitude of both the neck muscle
      electromyogram (EMG) and head kinematics was larger during ST trials than during
      RT trials. The EMG amplitude of ST trials was biased upward rather than scaled
      upward compared with the EMG amplitude of RT trials. 4. Over the 14 ST trials
      used in this experiment, no habituation of the reflex response was observed in
      the muscles studied. This absence of habituation was attributed to a combination
      of motor readiness and sensory facilitation. 5. The results of this experiment
      indicated that the neck muscle response evoked by a startling acoustic stimulus
      in the presence of motor readiness could be described as a facilitated startle
      reflex superimposed on a temporally advanced, pre-programmed, voluntary RT
      movement. Parallel reticular pathways to the neck muscle motoneurones are
      proposed as a possible explanation for the apparent summation of the startle and
      voluntary movement responses.

PMID- 11507180
TI  - Creation of killer poxvirus could have been predicted.

PMID- 11507179
TI  - Timing of postexercise protein intake is important for muscle hypertrophy with
      resistance training in elderly humans.
AB  - 1. Age-associated loss of skeletal muscle mass and strength can partly be
      counteracted by resistance training, causing a net synthesis of muscular
      proteins. Protein synthesis is influenced synergistically by postexercise amino
      acid supplementation, but the importance of the timing of protein intake remains
      unresolved. 2. The study investigated the importance of immediate (P0) or delayed
      (P2) intake of an oral protein supplement upon muscle hypertrophy and strength
      over a period of resistance training in elderly males. 3. Thirteen men (age, 74
      +/- 1 years; body mass index (BMI), 25 +/- 1 kg m(-2) (means +/- S.E.M.))
      completed a 12 week resistance training programme (3 times per week) receiving
      oral protein in liquid form (10 g protein, 7 g carbohydrate, 3 g fat) immediately
      after (P0) or 2 h after (P2) each training session. Muscle hypertrophy was
      evaluated by magnetic resonance imaging (MRI) and from muscle biopsies and muscle
      strength was determined using dynamic and isokinetic strength measurements. Body
      composition was determined from dual-energy X-ray absorptiometry (DEXA) and food
      records were obtained over 4 days. The plasma insulin response to protein
      supplementation was also determined. 4. In response to training, the cross
      sectional area of m. quadriceps femoris (54.6 +/- 0.5 to 58.3 +/- 0.5 cm(2)) and
      mean fibre area (4047 +/- 320 to 5019 +/- 615 microm(2)) increased in the P0
      group, whereas no significant increase was observed in P2. For P0 both dynamic
      and isokinetic strength increased, by 46 and 15 %, respectively (P < 0.05),
      whereas P2 only improved in dynamic strength, by 36 % (P < 0.05). No differences
      in glucose or insulin response were observed between protein intake at 0 and 2 h
      postexercise. 5. We conclude that early intake of an oral protein supplement
      after resistance training is important for the development of hypertrophy in
      skeletal muscle of elderly men in response to resistance training.

PMID- 11507181
TI  - Expression and functional characterization of bluetongue virus VP5 protein: role
      in cellular permeabilization.
AB  - Segment 5 of bluetongue virus (BTV) serotype 10, which encodes the outer capsid
      protein VP5, was tagged with glutathione S-transferase and expressed by a
      recombinant baculovirus. The recombinant protein was subsequently purified to
      homogeneity, and its possible biological role in virus infection was
      investigated. Purified VP5 was able to bind mammalian cells but was not
      internalized, which indicates it is not involved in receptor-mediated
      endocytosis. The purified VP5 protein was shown to be able to permeabilize
      mammalian and Culicoides insect cells, inducing cytotoxicity. Sequence analysis
      revealed that VP5 possesses characteristic structural features (including two
      amino-terminal amphipathic helices) compatible with virus penetration activity.
      To assess the role of each feature in the observed cytotoxicity, a series of
      deleted VP5 molecules were generated, and their expression and biological
      activity was compared with the parental molecule. VP5 derivatives that included
      the two amphipathic helices exhibited cytotoxicity, while those that omitted
      these sequences did not. To confirm their role in membrane destabilization two
      synthetic peptides (amino acids [aa] 1 to 20 and aa 22 to 41) encompassing the
      two helices and an additional peptide representing the adjacent downstream
      sequences were also assessed for their effect on the cell membrane. Both helices,
      but not the downstream VP5 sequence, exhibited cytotoxicity with the most-amino
      terminal helix (aa 1 to 20) showing a higher activity than the adjacent peptide
      (aa 22 to 41). Purified VP5 was shown to readily form trimers in solution, a
      feature of many proteins involved in membrane penetration. Taken together, these
      data support a role for VP5 in virus-cell penetration consistent with its
      revelation in the entry vesicle subsequent to cell binding and endocytosis.

PMID- 11507182
TI  - Kinetic analysis of the steps of the polyomavirus lytic cycle.
AB  - Kinetic studies of the accumulation of early and late transcripts, early and late
      proteins, genomes, and live virus, during the lytic cycle of murine polyomavirus
      wild-type A2, were carried out in synchronized NIH 3T3 cells released from G(0)
      by the addition of serum after infection. This first-time simultaneous analysis
      of all parameters of the virus life cycle led to new insights concerning the
      transcriptional control at the early-to-late transition. During the early phase,
      early transcripts were synthesized at very low levels, detectable only by reverse
      transcription-PCR, from 6 h postinfection (hpi). Large T protein could be
      detected by 8 hpi (while infected cells were in the G(1) phase). The level of
      expression of the middle T and small T proteins was lower than that of large T at
      all times, due, at least in part, to a splicing preference for the large-T 5'
      splice site at nucleotide 411. A large increase in the level of both early and
      late transcripts coincided closely with the detection in mid-S phase of viral
      genome amplification. Thereafter, both classes of transcripts continued to
      further accumulate up to the end of the experiments (48 hpi). In addition, during
      the late phase, "giant" multigenomic transcripts were synthesized from the early
      as well as the late promoter. Thus, a major type of transcriptional control
      appears to be applied similarly to the transcription of both early and late
      genes. This view differs from that in the literature, which highlights the
      enhancement of late transcription and the repression of early transcription.
      However, despite this parallel transcriptional control, additional regulations
      are applied which result in higher levels of late compared to early transcripts,
      as previously described. In the accompanying article, a key role for middle T
      and/or small T in this late-phase enhancement of early and late transcription is
      demonstrated (16). Other novel findings, e.g., the synthesis of a very abundant
      short early promoter proximal RNA, are also described.

PMID- 11507183
TI  - Role of middle T-small T in the lytic cycle of polyomavirus: control of the early
      to-late transcriptional switch and viral DNA replication.
AB  - A comparative analysis of the lytic cycle of wild-type polyomavirus and middle T
      and small T defective mutants was carried out in the A2 genetic background. The
      results contrast with those obtained in comparisons between the hr-t type and
      their middle-T small-T-producing partners as previously described (20). The A2
      derived mutants were found to share the maturation defect previously described
      for the hr-t mutants. However, their defect in DNA replication was more acute,
      resulting in a 5- to 100-fold decrease in the accumulation of viral genomes.
      Furthermore, their gene expression pattern was affected. A2-derived mutants
      displayed an early defect resulting in a 4- to 16-h delay in the expression of
      large T, and an alteration of the early-to-late transcriptional switch. In wild
      type A2 infection, this switch is characterized by a large increase in the
      accumulation of early transcripts followed by late transcripts after the
      appearance of middle T and small T proteins and the onset of viral DNA
      replication (L. Chen and M. M. Fluck, J. Virol. 75: 8368-8379, 2001). In the
      mutant infection, increases in both classes of transcripts were delayed and
      reduced, but the effect on early transcripts was more pronounced. As has been
      described previously for the hr-t mutants (E. Goldman, J. Hattori, and T.
      Benjamin, Cell 13:505-513, 1979), the magnitude of these defects depended upon
      experimental conditions. Experiments using cytosine beta-arabinofuranoside to
      reduce genome amplification suggest that the effect of middle T-small T on the
      transcriptional switch is not solely mediated by the effect of these protein(s)
      on increasing the number of templates. These data provide the first direct
      demonstration of an effect of middle T and/or small T in the viral transcription
      pattern during viral infection. The results agree with previous results obtained
      with plasmid reporters and with our understanding that the downstream targets of
      the middle T signaling pathway include three transcription factors that have
      binding sites in the enhancer domain that play a key regulatory role in the
      expression of the viral genes.

PMID- 11507184
TI  - A preponderance of CCR5(+) CXCR4(+) mononuclear cells enhances gastrointestinal
      mucosal susceptibility to human immunodeficiency virus type 1 infection.
AB  - The gastrointestinal mucosa harbors the majority of the body's CD4(+) cells and
      appears to be uniquely susceptible to human immunodeficiency virus type 1 (HIV-1)
      infection. We undertook this study to examine the role of differences in
      chemokine receptor expression on infection of mucosal mononuclear cells (MMCs)
      and peripheral blood mononuclear cells (PBMCs) by R5- and X4-tropic HIV-1. We
      performed in vitro infections of MMCs and PBMCs with R5- and X4-tropic HIV-1,
      engineered to express murine CD24 on the infected cell's surface, allowing for
      quantification of HIV-infected cells and their phenotypic characterization. A
      greater percentage of MMCs than PBMCs are infected by both R5- and X4-tropic HIV
      1. Significant differences exist in terms of chemokine receptor expression in the
      blood and gastrointestinal mucosa; mucosal cells are predominantly CCR5(+)
      CXCR4(+), while these cells make up less than 20% of the peripheral blood cells.
      It is this cell population that is most susceptible to infection with both R5-
      and X4-tropic HIV-1 in both compartments. Regardless of whether viral isolates
      were derived from the blood or mucosa of HIV-1-infected patients, HIV-1 p24
      production was greater in MMCs than in PBMCs. Further, the chemokine receptor
      tropism of these patient-derived viral isolates did not differ between
      compartments. We conclude that, based on these findings, the gastrointestinal
      mucosa represents a favored target for HIV-1, in part due to its large population
      of CXCR4(+) CCR5(+) target cells and not to differences in the virus that it
      contains.

PMID- 11507185
TI  - Differential regulation of hepatitis B virus gene expression by the Sp1
      transcription factor.
AB  - The expression of hepatitis B virus (HBV) genes is regulated by a number of
      transcription factors. One such factor, Sp1, has two binding sites in the core
      promoter and one in its upstream regulatory element, which is also known as the
      ENII enhancer. In this study, we have analyzed the effects of these three Sp1
      binding sites on the expression of HBV genes. Our results indicate that both Sp1
      binding sites in the core promoter are important for the transcription of the
      core RNA and the precore RNA. Moreover, while the downstream Sp1 site (the Sp1-1
      site) in the core promoter did not affect the transcription of the S gene and the
      X gene, the upstream Sp1 site (the Sp1-2 site) in the core promoter was found to
      negatively regulate the transcription of the S gene and the X gene, as removal of
      the latter led to enhancement of transcription of these two genes. The Sp1
      binding site in the ENII enhancer (the Sp1-3 site) positively regulates the
      expression of all of the HBV genes, as its removal by mutation suppressed the
      expression of all of the HBV genes. However, the suppressive effect of the Sp1-3
      site mutation on the expression of the S gene and the X gene was abolished if the
      two Sp1 sites in the core promoter were also mutated. These results indicate that
      Sp1 can serve both as a positive regulator and as a negative regulator for the
      expression of HBV genes. This dual activity may be important for the differential
      regulation of HBV gene expression.

PMID- 11507186
TI  - Critical role for alpha/beta and gamma interferons in persistence of lymphocytic
      choriomeningitis virus by clonal exhaustion of cytotoxic T cells.
AB  - Under conditions of high antigenic load during infection with invasive
      lymphocytic choriomeningitis virus (LCMV) strains, virus can persist by selective
      clonal exhaustion of antigen-specific CD8(+) T cells. In this work we studied the
      down-regulation of the virus-specific CD8(+)-T-cell response during a persistent
      infection of adult mice, with particular emphasis on the contribution of the
      interferon response in promoting host defense. Studies were conducted by
      infecting mice deficient in receptors for type I (alpha/beta interferon [IFN
      alpha/beta]), type II (IFN-gamma), and both type I and II IFNs with LCMV isolates
      that vary in their capacity to induce T-cell exhaustion. The main conclusions of
      this study are as follows. (i) IFNs play a critical role in LCMV infection by
      reducing viral loads in the initial stages of infection and thus modifying both
      the extent of CD8(+)-T-cell exhaustion and the course of infection. The
      importance of IFNs in this context varies with the biological properties of the
      LCMV strain. (ii) An inverse correlation exists between antigen persistence and
      responsiveness of virus-specific CD8(+) T cells. This results in distinct
      programs of activation or tolerance (functional unresponsiveness and/or physical
      elimination of antigen-specific cells) during acute and chronic virus infections,
      respectively. (iii) A successful immune response associated with definitive viral
      clearance requires an appropriate balance between cellular and humoral components
      of the immune system. We discuss the role of IFNs in influencing virus-specific T
      cells that determine the outcome of persistent infections.

PMID- 11507187
TI  - Feline leukemia virus DNA vaccine efficacy is enhanced by coadministration with
      interleukin-12 (IL-12) and IL-18 expression vectors.
AB  - The expectation that cell-mediated immunity is important in the control of feline
      leukemia virus (FeLV) infection led us to test a DNA vaccine administered alone
      or with cytokines that favored the development of a Th1 immune response. The
      vaccine consisted of two plasmids, one expressing the gag/pol genes and the other
      expressing the env gene of FeLV-A/Glasgow-1. The genetic adjuvants were plasmids
      encoding the feline cytokines interleukin-12 (IL-12), IL-18, or gamma interferon
      (IFN-gamma). Kittens were immunized by three intramuscular inoculations of the
      FeLV DNA vaccine alone or in combination with plasmids expressing IFN-gamma, IL
      12, or both IL-12 and IL-18. Control kittens were inoculated with empty plasmid.
      Following immunization, anti-FeLV antibodies were not detected in any kitten.
      Three weeks after the final immunization, the kittens were challenged by the
      intraperitoneal inoculation of FeLV-A/Glasgow-1 and were then monitored for a
      further 15 weeks for the presence of virus in plasma and, at the end of the
      trial, for latent virus in bone marrow. The vaccine consisting of FeLV DNA with
      the IL-12 and IL-18 genes conferred significant immunity, protecting completely
      against transient and persistent viremia, and in five of six kittens protecting
      against latent infection. None of the other vaccines provided significant
      protection.

PMID- 11507189
TI  - Phosphorylation of two serine residues regulates human T-cell leukemia virus type
      2 Rex function.
AB  - The function of the human T-cell leukemia virus (HTLV) Rex phosphoprotein is to
      increase the level of the viral structural and enzymatic gene products expressed
      from the incompletely spliced viral RNAs containing the Rex-responsive element.
      The phosphorylation of HTLV type 2 Rex (Rex-2), predominantly on serine residues,
      correlates with an altered conformation, as detected by a gel mobility shift, and
      is required for specific binding to its viral RNA target sequence. Thus, the
      phosphorylation state of Rex in the infected cell may be a switch that determines
      whether the virus exists in a latent or a productive state. A mutational analysis
      of Rex-2 that focused on serine and threonine residues was performed to identify
      regions or domains within Rex-2 important for function, with a specific emphasis
      on identifying Rex-2 phosphorylation mutants. We identified mutations near the
      carboxy terminus that disrupted a novel region or domain and abrogated Rex-2
      function. Mutant M17 (with S151A and S153A mutations) displayed reduced
      phosphorylation that correlated with reduced function. Replacement of both serine
      residues 151 and 153 with phosphomimetic aspartic acid restored Rex-2 function
      and locked Rex-2 in a phosphorylated active conformation. A mutant containing
      threonine residues at positions 151 and 153 displayed a phenotype
      indistinguishable from that of wild-type Rex. Furthermore, this same mutant
      showed increased threonine phosphorylation and decreased serine phosphorylation,
      providing conclusive evidence that one or both of these residues are
      phosphorylated in vivo. Our results provide the first direct evidence that the
      phosphorylation of Rex-2 is important for function. Further understanding of HTLV
      Rex phosphorylation will provide insight into the regulatory control of HTLV
      replication and ultimately the pathobiology of HTLV.

PMID- 11507188
TI  - Chimeric plant virus particles as immunogens for inducing murine and human immune
      responses against human immunodeficiency virus type 1.
AB  - The high-yield expression of a neutralizing epitope from human immunodeficiency
      virus type 1 (HIV-1) on the surface of a plant virus and its immunogenicity are
      presented. The highly conserved ELDKWA epitope from glycoprotein (gp) 41 was
      expressed as an N-terminal translational fusion with the potato virus X (PVX)
      coat protein. The resulting chimeric virus particles (CVPs), purified and used to
      immunize mice intraperitoneally or intranasally, were able to elicit high levels
      of HIV-1-specific immunoglobulin G (IgG) and IgA antibodies. Furthermore, the
      human immune response to CVPs was studied with severe combined immunodeficient
      mice reconstituted with human peripheral blood lymphocytes (hu-PBL-SCID). hu-PBL
      SCID mice immunized with CVP-pulsed autologous dendritic cells were able to mount
      a specific human primary antibody response against the gp41-derived epitope.
      Notably, sera from both normal and hu-PBL-SCID mice showed an anti-HIV-1
      neutralizing activity. Thus, PVX-based CVPs carrying neutralizing epitopes can
      offer novel perspectives for the development of effective vaccines against HIV
      and, more generally, for the design of new vaccination strategies in humans.

PMID- 11507190
TI  - Frequent substitution polymorphisms in African green monkey CCR5 cluster at
      critical sites for infections by simian immunodeficiency virus SIVagm, implying
      ancient virus-host coevolution.
AB  - In contrast to humans, several primate species are believed to have harbored
      simian immunodeficiency viruses (SIVs) since ancient times. In particular, the
      geographically dispersed species of African green monkeys (AGMs) are all infected
      with highly diversified SIVagm viruses at high prevalences (greater than 50% of
      sexually mature individuals) without evident diseases, implying that the
      progenitor monkeys were infected prior to their dispersal. If this is correct,
      AGMs would be expected to have accumulated frequent resistance-conferring
      polymorphisms in host genes that are important for SIV replication. Accordingly,
      we analyzed the coding sequences of the CCR5 coreceptors from 26 AGMs (52
      alleles) in distinct populations of the four species. These samples contained 29
      nonsynonymous coding changes and only 15 synonymous nucleotide substitutions,
      implying intense functional selection. Moreover, 24 of the resulting amino acid
      substitutions were tightly clustered in the CCR5 amino terminus (D13N in the
      vervets and Y14N in the tantalus species) or in the first extracellular loop
      (Q93R and Q93K in all species). The Y14N substitution was extremely frequent in
      the 12 wild-born African tantalus, with 7 monkeys being homozygous for this
      substitution and 4 being heterozygous. Although two of these heterozygotes and
      the only wild-type homozygote were naturally infected with SIVagm, none of the
      Y14N homozygotes were naturally infected. A focal infectivity assay for SIVagm
      indicated that all five tested SIVagms efficiently use CCR5 as a coreceptor and
      that they also use CXCR6 (STRL33/Bonzo) and GPR15 (BOB) with lower efficiencies
      but not CXCR4. Interestingly, the D13N, Y14N, Q93R, and Q93K substitutions in AGM
      CCR5 all strongly inhibited infections by the SIVagm isolates in vitro. The Y14N
      substitution eliminates a tyrosine sulfation site that is important for
      infections and results in partial N-linked glycosylation (i.e., 60% efficiency)
      at this position. Nevertheless, the CCR5(Y14N) component that lacks an N-linked
      oligosaccharide binds the chemokine MIP-lbeta with a normal affinity and is fully
      active in signal transduction. Similarly, D13N and Q93R substitutions did not
      interfere with signal transduction. Thus, the common substitution polymorphisms
      in AGM CCR5 strongly inhibit SIVagm infections while substantially preserving
      chemokine signaling. In contrast, polymorphisms of human CCR5 are relatively
      infrequent, and the amino acid substitutions are randomly situated and generally
      without effects on coreceptor function. These results support an ancient
      coevolution of AGMs and SIVagm viruses and establish AGMs as a highly informative
      model for learning about host proteins that play critical roles in
      immunodeficiency virus infections.

PMID- 11507191
TI  - Examining human T-lymphotropic virus type 1 infection and replication by cell
      free infection with recombinant virus vectors.
AB  - A sensitive and quantitative cell-free infection assay, utilizing recombinant
      human T-cell leukemia virus type 1 (HTLV-1)-based vectors, was developed in order
      to analyze early events in the virus replication cycle. Previous difficulties
      with the low infectivity and restricted expression of the virus have prevented a
      clear understanding of these events. Virus stocks were generated by transfecting
      cells with three plasmids: (i) a packaging plasmid encoding HTLV-1 structural and
      regulatory proteins, (ii) an HTLV-1 transfer vector containing either firefly
      luciferase or enhanced yellow fluorescent protein genes, and (iii) an envelope
      expression plasmid. Single-round infections were initiated by exposing target
      cells to filtered supernatants and quantified by assaying for luciferase activity
      in cell extracts or by enumerating transduced cells by flow cytometry.
      Transduction was dependent on reverse transcription and integration of the
      recombinant virus genome, as shown by the effects of the reverse transcriptase
      inhibitor 3'-azido-3'-deoxythymidine (AZT) and by mutation of the integrase gene
      in the packaging vector, respectively. The 50% inhibitory concentration of AZT
      was determined to be 30 nM in this HTLV-1 replication system. The stability of
      HTLV-1 particles, pseudotyped with either vesicular stomatitis virus G protein or
      HTLV-1 envelope, was typical of retroviruses, exhibiting a half-life of
      approximately 3.5 h at 37 degrees C. The specific infectivity of recombinant HTLV
      1 virions was at least 3 orders of magnitude lower than that of analogous HIV-1
      particles, though both were pseudotyped with the same envelope. Thus, the low
      infectivity of HTLV-1 is determined in large part by properties of the core
      particle and by the efficiency of postentry processes.

PMID- 11507192
TI  - DNA vaccination with the Hantaan virus M gene protects Hamsters against three of
      four HFRS hantaviruses and elicits a high-titer neutralizing antibody response in
      Rhesus monkeys.
AB  - Four hantaviruses-Hantaan virus (HTNV), Seoul virus (SEOV), Dobrava virus (DOBV)
      and Puumala virus-are known to cause hemorrhagic fever with renal syndrome (HFRS)
      in Europe and Asia. HTNV causes the most severe form of HFRS (5 to 15% case
      fatality rate) and afflicts tens of thousands of people annually. Previously, we
      demonstrated that DNA vaccination with a plasmid expressing the SEOV M gene
      elicited neutralizing antibodies and protected hamsters against infection with
      SEOV and HTNV. Here, we report the construction and evaluation of a DNA vaccine
      that expresses the HTNV M gene products, G1 and G2. DNA vaccination of hamsters
      with the HTNV M gene conferred sterile protection against infection with HTNV,
      SEOV, and DOBV. DNA vaccination of rhesus monkeys with either the SEOV or HTNV M
      gene elicited high levels of neutralizing antibodies. These are the first
      immunogenicity data for hantavirus DNA vaccines in nonhuman primates. Because a
      neutralizing antibody response is considered a surrogate marker for protective
      immunity in humans, our protection data in hamsters combined with the
      immunogenicity data in monkeys suggest that hantavirus M gene-based DNA vaccines
      could protect humans against the most severe forms of HFRS.

PMID- 11507193
TI  - Role of chimeric murine leukemia virus env beta-turn polyproline spacers in
      receptor cooperation.
AB  - We have previously reported a set of Moloney murine leukemia virus derived
      envelopes retargeted to the Pit-2 phosphate transporter molecule, by insertion of
      the Pit-2 binding domain (BD) at the N terminus of the ecotropic retroviral
      envelope glycoproteins (S. Valsesia-Wittmann et al., J. Virol. 70:2059-2064,
      1996). The resulting chimeric envelopes share two BDs: an additional N-terminal
      BD (Pit-2 BD) and the BD of the ecotropic envelope (mCAT-1 BD). By inserting a
      variety of different amino acid spacers between the two binding domains, we
      showed that retroviruses can potentially use the targeted cell surface receptor
      Pit-2, the ecotropic retroviral receptor mCAT-1, or both receptors cooperatively
      for entry into target cell (S. Valsesia-Wittmann et al., EMBO J 6:1214-1223,
      1997). An extreme example of receptor cooperativity was encountered when
      envelopes with specific proline-rich interdomain spacers (PRO spacers) were
      tested: both receptors had to be coexpressed at the surface of the targeted cells
      to cooperatively allow infection. Here, we characterized the role of PRO spacer
      in the cooperation of receptors. We have shown that the particular organization
      of the PRO spacer-a beta-turn polyproline-was responsible for the cooperative
      effect. In the native configuration of the viruses, the structure masked the
      regions located downstream of the PRO spacer, thus the mCAT-1 BD. After
      interaction with the targeted Pit-2 receptor, the BD of the backbone envelope
      became accessible, and we demonstrated that interaction between the mCAT-1 BD and
      the mCAT-1 receptor is absolutely necessary. This interaction leads to natural
      fusion triggering and entry of viruses into targeted cells.

PMID- 11507194
TI  - RNA splicing at human immunodeficiency virus type 1 3' splice site A2 is
      regulated by binding of hnRNP A/B proteins to an exonic splicing silencer
      element.
AB  - The synthesis of human immunodeficiency virus type 1 (HIV-1) mRNAs is a complex
      process by which more than 30 different mRNA species are produced by alternative
      splicing of a single primary RNA transcript. HIV-1 splice sites are used with
      significantly different efficiencies, resulting in different levels of mRNA
      species in infected cells. Splicing of Tat mRNA, which is present at relatively
      low levels in infected cells, is repressed by the presence of exonic splicing
      silencers (ESS) within the two tat coding exons (ESS2 and ESS3). These ESS
      elements contain the consensus sequence PyUAG. Here we show that the efficiency
      of splicing at 3' splice site A2, which is used to generate Vpr mRNA, is also
      regulated by the presence of an ESS (ESSV), which has sequence homology to ESS2
      and ESS3. Mutagenesis of the three PyUAG motifs within ESSV increases splicing at
      splice site A2, resulting in increased Vpr mRNA levels and reduced skipping of
      the noncoding exon flanked by A2 and D3. The increase in Vpr mRNA levels and the
      reduced skipping also occur when splice site D3 is mutated toward the consensus
      sequence. By in vitro splicing assays, we show that ESSV represses splicing when
      placed downstream of a heterologous splice site. A1, A1(B), A2, and B1 hnRNPs
      preferentially bind to ESSV RNA compared to ESSV mutant RNA. Each of these
      proteins, when added back to HeLa cell nuclear extracts depleted of ESSV-binding
      factors, is able to restore splicing repression. The results suggest that
      coordinate repression of HIV-1 RNA splicing is mediated by members of the hnRNP
      A/B protein family.

PMID- 11507195
TI  - Human immunodeficiency virus type 1 IIIB selected for replication in vivo
      exhibits increased envelope glycoproteins in virions without alteration in
      coreceptor usage: separation of in vivo replication from macrophage tropism.
AB  - Analysis of viral replication and pathogenicity after in vivo selection of human
      immunodeficiency virus type 1 (HIV-1) attenuated in vitro will help to define the
      functions involved in replication and pathogenesis in vivo. Using the SCID-hu
      Thy/Liv mouse and human fetal thymus organ culture as in vivo models, we
      previously defined HIV-1 env determinants (HXB2/LW) which were reverted for
      replication in vivo (L. Su et al., Virology 227:46-52, 1997). In this study, we
      examined the replication of four highly related HIV-1 clones directly derived
      from Lai/IIIB or after selection in vivo to investigate the envelope gp120
      determinants associated with replication in macrophages and in the thymus models
      in vivo. The LW/C clone derived from the IIIB-infected laboratory worker and
      HXB2/LW both efficiently infected monocyte-derived macrophages (MDM) and the
      human thymus. Although the laboratory worker (LW) isolates showed altered tropism
      from IIIB, they still predominantly used CXCR4 as coreceptors for infecting
      peripheral blood mononuclear cells, macrophages, and the thymus. Interestingly, a
      single amino acid mutation in the V3 loop associated with resistance to
      neutralizing antibodies was also essential for the replication activity of the LW
      virus in the thymus models but not for its activity in infecting MDM. The LW
      virions were equally sensitive to a CXCR4 antagonist. We further demonstrated
      that the LW HIV-1 isolate selected in vivo produced more infectious viral
      particles that contained higher levels of the Env protein gp120. Thus, selection
      of the laboratory-attenuated Lai/IIIB isolate in vivo leads to altered tropism
      but not coreceptor usage of the virus. The acquired replication activity in vivo
      is correlated with an early A-to-T mutation in the V3 loop and increased virion
      association of HIV-1 Env gp120, but it is genetically separable from the acquired
      replication activity in macrophages.

PMID- 11507196
TI  - A mutation in the latency-related gene of bovine herpesvirus 1 leads to impaired
      ocular shedding in acutely infected calves.
AB  - Bovine herpesvirus 1 (BHV-1) is an important pathogen of cattle, and infection is
      usually initiated in the ocular or nasal cavity. Like other alphaherpesviruses,
      BHV-1 establishes latency in sensory neurons but has the potential of
      reactivating from latency and spreading. The only abundant viral transcript
      expressed during latency is the latency-related (LR) RNA, which is alternatively
      spliced in trigeminal ganglia during acute infection (L. R. Devireddy and C.
      Jones, J. Virol. 72:7294-7301, 1998). LR gene products inhibit cell cycle
      progression (Y. Jiang, A. Hossain, M. T. Winkler, T. Holt, A. Doster, and C.
      Jones, J. Virol. 72:8133-8142, 1998) and chemically induced apoptosis (J. Ciacci
      Zannela, M. Stone, G. Henderson, and C. Jones. J. Virol. 73:9734-9740, 1999).
      Although these studies suggest that LR gene products play an important role in
      the latency/pathogenesis of BHV-1, construction of a mutant is necessary to test
      this hypothesis. Because the bICP0 gene overlaps and is antisense to the LR gene,
      it was necessary to mutate the LR gene without altering bICP0 expression. This
      was accomplished by inserting three stop codons near the beginning of the LR RNA,
      thus interfering with expression of proteins expressed by the LR RNA. The LR
      mutant virus grew with wild-type (WT) efficiency in bovine kidney (MDBK) cells
      and expressed bICP0 at least as efficiently as WT BHV-1 or the LR rescued virus.
      When calves were infected with the LR mutant, we observed a dramatic decrease (3
      to 4 log units) in ocular shedding during acute infection relative to WT or the
      LR rescued virus. In contrast, shedding of the LR mutant from the nasal cavity
      was not significantly different from that of the WT or the LR rescued virus.
      Calves infected with the LR mutant exhibited mild clinical symptoms, but they
      seroconverted. Neutralizing antibody titers were lower in calves infected with
      the LR mutant, confirming reduced growth. In summary, this study suggests that an
      LR protein promotes ocular shedding during acute infection of calves.

PMID- 11507197
TI  - Effect of alpha interferon on the hepatitis C virus replicon.
AB  - Chronic hepatitis C virus (HCV) infections can be cured only in a fraction of
      patients treated with alpha interferon (IFN-alpha) and ribavirin combination
      therapy. The mechanism of the IFN-alpha response against HCV is not understood,
      but evidence for a role for viral nonstructural protein 5A (NS5A) in IFN
      resistance has been provided. To elucidate the mechanism by which NS5A and
      possibly other viral proteins inhibit the cellular antiviral program, we have
      constructed a subgenomic replicon from a known infectious HCV clone and
      demonstrated that it has an approximately 1,000-fold-higher transduction
      efficiency than previously used subgenomes. We found that IFN-alpha reduced
      replication of HCV subgenomic replicons approximately 10-fold. The estimated half
      life of viral RNA in the presence of the cytokine was about 12 h. HCV replication
      was sensitive to IFN-alpha independently of whether the replicon expressed an
      NS5A protein associated with sensitivity or resistance to the cytokine.
      Furthermore, our results indicated that HCV replicons can persist in Huh7 cells
      in the presence of high concentrations of IFN-alpha. Finally, under our
      conditions, selection for IFN-alpha-resistant variants did not occur.

PMID- 11507198
TI  - Activation of human immunodeficiency virus transcription in T cells revisited: NF
      kappaB p65 stimulates transcriptional elongation.
AB  - Human immunodeficiency virus type 1 (HIV-1) is able to establish a persistent
      latent infection during which the integrated provirus remains transcriptionally
      silent. Viral transcription is stimulated by NF-kappaB, which is activated
      following the exposure of infected T cells to antigens or mitogens. Although it
      is commonly assumed that NF-kappaB stimulates transcriptional initiation alone,
      we have found using RNase protection assays that, in addition to stimulating
      initiation, it can also stimulate elongation from the HIV-1 long terminal repeat.
      When either Jurkat or CCRF/CEM cells were activated by the mitogens phorbol
      myristate acetate and phytohemagglutinin, elongation, as measured by the
      proportion of full-length transcripts, increased two- to fourfold, even in the
      absence of Tat. Transfection of T cells with plasmids carrying the different
      subunits of NF-kappaB demonstrated that the activation of transcriptional
      elongation is mediated specifically by the p65 subunit. It seems likely that
      initiation is activated because of NF-kappaB's ability to disrupt chromatin
      structures through the recruitment of histone acetyltransferases. To test whether
      p65 could stimulate elongation under conditions where it did not affect histone
      acetylation, cells were treated with the histone deacetylase inhibitor
      trichostatin A. Remarkably, addition of p65 to the trichostatin A-treated cell
      lines resulted in a dramatic increase in transcription elongation, reaching
      levels equivalent to those observed in the presence of Tat. We suggest that the
      activation of elongation by NF-kappaB p65 involves a distinct biochemical
      mechanism, probably the activation of carboxyl-terminal domain kinases at the
      promoter.

PMID- 11507199
TI  - Biochemical characterization of the helper component of Cauliflower mosaic virus.
AB  - The helper component of Cauliflower mosaic virus is encoded by viral gene II.
      This protein (P2) is dispensable for virus replication but required for aphid
      transmission. The purification of P2 has never been reported, and hence its
      biochemical properties are largely unknown. We produced the P2 protein via a
      recombinant baculovirus with a His tag fused at the N terminus. The fusion
      protein was purified by affinity chromatography in a soluble and biologically
      active form. Matrix-assisted laser desorption time-of-flight mass spectrometry
      demonstrated that P2 is not posttranslationally modified. UV circular dichroism
      revealed the secondary structure of P2 to be 23% alpha-helical. Most alpha
      helices are suggested to be located in the C-terminal domain. Using size
      exclusion chromatography and aphid transmission testing, we established that the
      active form of P2 assembles as a huge soluble oligomer containing 200 to 300
      subunits. We further showed that P2 can also polymerize as long paracrystalline
      filaments. We mapped P2 domains involved in P2 self-interaction, presumably
      through coiled-coil structures, one of which is proposed to form a parallel
      trimer. These regions have previously been reported to also interact with viral
      P3, another protein involved in aphid transmission. Possible interference between
      the two types of interaction is discussed with regard to the biological activity
      of P2.

PMID- 11507200
TI  - Hepatitis delta virus minimal substrates competent for editing by ADAR1 and
      ADAR2.
AB  - A host-mediated RNA-editing event allows hepatitis delta virus (HDV) to express
      two essential proteins, the small delta antigen (HDAg-S) and the large delta
      antigen (HDAg-L), from a single open reading frame. One or several members of the
      ADAR (adenosine deaminases that act on RNA) family are thought to convert the
      adenosine to an inosine (I) within the HDAg-S amber codon in antigenomic RNA. As
      a consequence of replication, the UIG codon is converted to a UGG (tryptophan
      [W]) codon in the resulting HDAg-L message. Here, we used a novel reporter system
      to monitor the editing of the HDV amber/W site in the absence of replication. In
      cultured cells, we observed that both human ADAR1 (hADAR1) and hADAR2 were
      capable of editing the amber/W site with comparable efficiencies. We also defined
      the minimal HDV substrate required for hADAR1- and hADAR2-mediated editing. Only
      24 nucleotides from the amber/W site were sufficient to enable efficient editing
      by hADAR1. Hence, the HDV amber/W site represents the smallest ADAR substrate yet
      identified. In contrast, the minimal substrate competent for hADAR2-mediated
      editing contained 66 nucleotides.

PMID- 11507201
TI  - An Epstein-Barr virus isolated from a lymphoblastoid cell line has a 16-kilobase
      pair deletion which includes gp350 and the Epstein-Barr virus nuclear antigen 3A.
AB  - Epstein-Barr virus (EBV) is associated with human cancers, including
      nasopharyngeal carcinoma, Burkitt's lymphoma, gastric carcinoma and, somewhat
      controversially, breast carcinoma. EBV infects and efficiently transforms human
      primary B lymphocytes in vitro. A number of EBV-encoded genes are critical for
      EBV-mediated transformation of human B lymphocytes. In this study we show that an
      EBV-infected lymphoblastoid cell line obtained from the spontaneous outgrowth of
      B cells from a leukemia patient contains a deletion, which involves a region of
      approximately 16 kbp. This deletion encodes major EBV genes involved in both
      infection and transformation of human primary B lymphocytes and includes the
      glycoprotein gp350, the entire open reading frame of EBNA3A, and the amino
      terminal region of EBNA3B. A fusion protein created by this deletion, which lies
      between the BMRF1 early antigen and the EBNA3B latent antigen, is truncated
      immediately downstream of the junction 21 amino acids into the region of the
      EBNA3B sequence, which is out of frame with respect to the EBNA3B protein
      sequence, and indicates that EBNA3B is not expressed. The fusion is from EBV
      coordinate 80299 within the BMRF1 sequence to coordinate 90998 in the EBNA3B
      sequence. Additionally, we have shown that there is no detectable induction in
      viral replication observed when SNU-265 is treated with phorbol esters, and no
      transformants were detected when supernatant is used to infect primary B
      lymphocytes after 8 weeks in culture. Therefore, we have identified an EBV genome
      with a major deletion in critical genes involved in mediating EBV infection and
      the transformation of human primary B lymphocytes that is incompetent for
      replication of this naturally occurring EBV isolate.

PMID- 11507203
TI  - Identification of the immunodominant H-2K(k)-restricted cytotoxic T-cell epitope
      in the Borna disease virus nucleoprotein.
AB  - Borna disease virus (BDV)-induced immunopathology in mice is most prominent in
      strains carrying the major histocompatibility complex H-2k allele and is mediated
      by CD8(+) T cells that are directed against the viral nucleoprotein p40. We now
      identified the highly conserved octamer peptide TELEISSI, located between amino
      acid residues 129 and 136 of BDV p40, as a potent H-2K(k)-restricted cytotoxic T
      cell (CTL) epitope. When added to the culture medium of L929 target cells,
      TELEISSI conferred sensitivity to lysis by CTLs isolated from brains of BDV
      infected MRL mice with acute neurological disease. Vaccinia virus-mediated
      expression of a p40 variant with mutations in the two K(k)-specific anchor
      residues of the TELEISSI peptide (p40(E130K,I136T)) did not sensitize L929 target
      cells for lysis by BDV-specific CTLs, whereas expression of wild-type p40 did.
      Furthermore, unlike vaccination with wild-type p40, vaccination of persistently
      infected symptomless B10.BR mice with p40(E130K,I136T) did not result in central
      nervous system inflammation and neurological disease. These results demonstrate
      that TELEISSI is the immunodominant CTL epitope of BDV p40 in H-2k mice.

PMID- 11507202
TI  - Amino acids 257 to 288 of mouse p48 control the cooperation of polyomavirus large
      T antigen, replication protein A, and DNA polymerase alpha-primase to synthesize
      DNA in vitro.
AB  - Although p48 is the most conserved subunit of mammalian DNA polymerase alpha
      primase (pol-prim), the polypeptide is the major species-specific factor for
      mouse polyomavirus (PyV) DNA replication. Human and murine p48 contain two
      regions (A and B) that show significantly lower homology than the rest of the
      protein. Chimerical human-murine p48 was prepared and coexpressed with three wild
      type subunits of pol-prim, and four subunit protein complexes were purified. All
      enzyme complexes synthesized DNA on single-stranded (ss) DNA and replicated
      simian virus 40 DNA. Although the recombinant protein complexes physically
      interacted with PyV T antigen (Tag), we determined that the murine region A
      mediates the species specificity of PyV DNA replication in vitro. More precisely,
      the nonconserved phenylalanine 262 of mouse p48 is crucial for this activity, and
      pol-prim with mutant p48, h-S262F, supports PyV DNA replication in vitro. DNA
      synthesis on RPA-bound ssDNA revealed that amino acid (aa) 262, aa 266, and aa
      273 to 288 are involved in the functional cooperation of RPA, pol-prim, and PyV
      Tag.

PMID- 11507204
TI  - Evidence for early local viral replication and local production of antiviral
      immunity upon mucosal simian-human immunodeficiency virus SHIV(89.6) infection in
      Macaca nemestrina.
AB  - Transmission of human immunodeficiency virus type 1 (HIV-1) is largely a result
      of heterosexual exposure, leading many investigators to evaluate mucosal vaccines
      for protection against intravaginal (i.vag.) transmission in macaque models of
      AIDS. Relatively little is known, however, about the dynamics of viral
      replication and the ensuing immune response following mucosal infection. We have
      utilized a simian-human immunodeficiency virus (SHIV) to study the differences in
      viremia, CD4 T-cell percentages, and mucosal and systemic anti-SHIV humoral and
      cellular immune responses during primary infection of animals infected either
      intravenously (i.v.) or i.vag. Positive viral cocultures, peripheral blood
      mononuclear cell viral load peaks, and CD4 cell declines were delayed by 1 week
      in the i.vag. inoculated animals compared to the animals infected i.v.,
      demonstrating delayed viral spreading to the periphery. In contrast, mucosal anti
      SHIV antibody levels were greater in magnitude and arose more rapidly and mucosal
      CD8(+) T-cell responses were enhanced in the i.vag. group animals, whereas both
      the magnitudes and times of onset of systemic immune responses for the animals in
      the two groups did not differ. These observations demonstrate that
      compartmentalization of viral replication and induction of local antiviral
      immunity occur in the genital tract early after i.vag. but not i.v. inoculation.
      Induction of mucosal immunity to target this local, contained replication should
      be a goal in HIV vaccine development.

PMID- 11507205
TI  - PA subunit from influenza virus polymerase complex interacts with a cellular
      protein with homology to a family of transcriptional activators.
AB  - The PA subunit of the influenza virus polymerase complex is a phosphoprotein that
      induces proteolytic degradation of coexpressed proteins. Point mutants with
      reduced proteolysis induction reconstitute viral ribonucleoproteins defective in
      replication but not in transcriptional activity. To look for cellular factors
      that could associate with PA protein, we have carried out a yeast two-hybrid
      screen. Using a human kidney cDNA library, we identified two different
      interacting clones. One of them was identified as the human homologue of a
      previously described cDNA clone from Gallus gallus called CLE. The human gene
      encodes a protein of 36 kDa (hCLE) and is expressed ubiquitously in all human
      organs tested. The interaction of PA and hCLE was also observed with purified
      proteins in vitro by using pull-down and pep-spot experiments. Mapping of the
      interaction showed that hCLE interacts with PA subunit at two regions (positions
      493 to 512 and 557 to 574) in the PA protein sequence. Immunofluorescence studies
      showed that the hCLE protein localizes in both the nucleus and the cytosol,
      although with a predominantly cytosolic distribution. hCLE was found associated
      with active, highly purified virus ribonucleoproteins reconstituted in vivo from
      cloned cDNAs, suggesting that PA-hCLE interaction is functionally relevant.
      Searches in the databases showed that hCLE has 38% sequence homology to the
      central region of the yeast factor Cdc68, which modulates transcription by
      interaction with transactivators. Similar homologies were found with the other
      members of the Cdc68 homologue family of transcriptional activators, including
      the human FACT protein.

PMID- 11507206
TI  - Sensitivity of human immunodeficiency virus type 1 to fusion inhibitors targeted
      to the gp41 first heptad repeat involves distinct regions of gp41 and is
      consistently modulated by gp120 interactions with the coreceptor.
AB  - T-20 is a synthetic peptide that corresponds to 36 amino acids within the C
      terminal heptad repeat region (HR2) of human immunodeficiency virus type 1 (HIV
      1) gp41. T-20 has been shown to potently inhibit viral replication of HIV-1 both
      in vitro and in vivo and is currently being evaluated in a Phase III clinical
      trial. T-649 is an inhibitory peptide that also corresponds to 36 amino acids
      within HR2. This sequence overlaps the T-20 sequence but is shifted 10 residues
      toward the N terminus of gp41. Both inhibitors are thought to exert their
      antiviral activity by interfering with the conformational changes that occur
      within gp41 to promote membrane fusion following gp120 interactions with CD4 and
      coreceptor molecules. We have shown previously that coreceptor specificity
      defined by the V3 loop of gp120 modulates sensitivity to T-20 and that a critical
      region within the N-terminal heptad repeat (HR1) of gp41 is the major determinant
      of sensitivity (C. A. Derdeyn et al., J. Virol. 74:8358-8367, 2000). This report
      shows that (i) regions within gp41 distinct from those associated with T-20
      sensitivity govern the baseline sensitivity to T-649 and (ii) T-649 sensitivity
      of chimeric viruses that contain sequences derived from CXCR4- and CCR5-specific
      envelopes is also modulated by coreceptor specificity. Moreover, the pattern of
      sensitivity of CCR5-specific chimeras with only minor differences in their V3
      loop was consistent for both inhibitors, suggesting that the individual affinity
      for coreceptor may influence accessibility of these inhibitors to their target
      sequence. Finally, an analysis of the sensitivity of 55 primary, inhibitor-naive
      HIV-1 isolates found that higher concentrations of T-20 (P < 0.001) and T-649 (P
      = 0.016) were required to inhibit CCR5-specific viruses compared to viruses that
      utilize CXCR4. The results presented here implicate gp120-coreceptor interactions
      in driving the complex conformational changes that occur in gp41 to promote
      fusion and entry and suggest that sensitivity to different HR1-directed fusion
      inhibitors is governed by distinct regions of gp41 but is consistently modulated
      by coreceptor specificity.

PMID- 11507207
TI  - Terminal nucleotidyl transferase activity of recombinant Flaviviridae RNA
      dependent RNA polymerases: implication for viral RNA synthesis.
AB  - Recombinant hepatitis C virus (HCV) RNA-dependent RNA polymerase (RdRp) was
      reported to possess terminal transferase (TNTase) activity, the ability to add
      nontemplated nucleotides to the 3' end of viral RNAs. However, this TNTase was
      later purported to be a cellular enzyme copurifying with the HCV RdRp. In this
      report, we present evidence that TNTase activity is an inherent function of HCV
      and bovine viral diarrhea virus RdRps highly purified from both prokaryotic and
      eukaryotic cells. A change of the highly conserved GDD catalytic motif in the HCV
      RdRp to GAA abolished both RNA synthesis and TNTase activity. Furthermore, the
      nucleotides added via this TNTase activity are strongly influenced by the
      sequence near the 3' terminus of the viral template RNA, perhaps accounting for
      the previous discrepant observations between RdRp preparations. Last, the RdRp
      TNTase activity was shown to restore the ability to direct initiation of RNA
      synthesis in vitro on an initiation-defective RNA substrate, thereby implicating
      this activity in maintaining the integrity of the viral genome termini.

PMID- 11507208
TI  - Mechanisms involved in stimulation of human immunodeficiency virus type 1
      replication by aminooxypentane RANTES.
AB  - Aminooxypentane (AOP)-RANTES is a potent inhibitor of nonsyncytium-inducing
      (NSI), CCR5-tropic (R5) human immunodeficiency virus type 1 (HIV-1) isolates.
      Although classical chemotactic responses are not induced in primary leukocytes by
      AOP-RANTES, recent studies suggest that a remnant of cell signaling occurs upon
      binding of receptor to this compound. We have detected a breakthrough of NSI/R5
      replication from the inhibitory effects of high AOP-RANTES concentrations (<100
      nM). A stimulation of different primary syncytium-inducing (SI), CXCR4-tropic
      (X4) HIV-1 isolates was also observed in the presence of AOP-RANTES. This
      stimulation was also observed after 110 h in PCR and RT-PCR for minus-strand
      strong-stop DNA and unspliced and multiply spliced RNA, respectively. However,
      there was significant variability between different SI/X4 or NSI/R5 HIV-1
      isolates with regard to this AOP-RANTES-mediated stimulation or breakthrough,
      respectively. To further define the mechanism(s) responsible for this AOP-RANTES
      effect, we performed detailed retroviral replication studies with an NSI/R5 (B
      92BR021) and SI/X4 (D-92UG021) HIV-1 isolate in the presence of the drug.
      Treatment of peripheral blood mononuclear cells with 125 nM AOP-RANTES and virus
      did not alter coreceptor expression, HIV-1 entry, reverse transcription, or mRNA
      transcription from the long terminal repeat, but it did result in increased HIV-1
      integration. This AOP-RANTES-mediated increase in HIV-1 integration was
      diminished by treatment with pertussis toxin. Phosphorylation of the mitogen
      activated protein kinase (MAPK) isoforms, extracellular signal-regulated kinase 1
      (ERK1) and ERK2, was increased in a CD4(+) CCR5(+) U87 cell line treated with AOP
      RANTES or with an NSI/R5 HIV-1 isolate. These findings suggest that AOP-RANTES
      may induce a MAPK/ERK signal transduction pathway upon binding to a G-protein
      coupled receptor. MAPK/ERK1 and -2 appear to phosphorylate the HIV-1
      preintegration complex, a step necessary for nuclear translocation and successful
      integration.

PMID- 11507209
TI  - Both Lymantria dispar nucleopolyhedrovirus enhancin genes contribute to viral
      potency.
AB  - Enhancins are a group of proteins first identified in granuloviruses (GV) that
      have the ability to enhance nuclear polyhedrosis virus potency. We had previously
      identified an enhancin gene (E1) in the Lymantria dispar multinucleocapsid
      nucleopolyhedrovirus (LdMNPV) (D. S. Bischoff and J. M. Slavicek, J. Virol.
      71:8133-8140, 1997). Inactivation of the E1 gene product within the viral genome
      lowered viral potency by an average of 2.9-fold. A second enhancin gene (E2) was
      identified when the entire genome of LdMNPV was sequenced (Kuzio et al., Virology
      253:17-34, 1999). The E2 protein exhibits approximately 30% amino acid identity
      to the LdMNPV E1 protein as well as the enhancins from Trichoplusia ni GV,
      Pseudaletia unipuncta GV, Helicoverpa armigera GV, and Xestia c-nigrum GV.
      Northern analysis of viral RNA indicated that the E2 gene transcripts are
      expressed at late times postinfection from a consensus baculovirus late promoter.
      The effect of the enhancin proteins on viral potency was investigated through
      bioassay using two recombinant viruses, one with a deletion in the E2 gene
      (E2del) and a second with deletion mutations in both enhancin genes (E1delE2del).
      The enhancin gene viral constructs were verified by Southern analysis and shown
      not to produce enhancin gene transcripts by Northern analysis. The E2del virus
      exhibited an average decrease in viral potency of 1.8-fold compared to wild-type
      virus. In the same bioassays, the recombinant virus E1cat, which does not produce
      an E1 gene transcript, exhibited an average decrease in viral potency of 2.3-fold
      compared to control virus. The E1delE2del virus exhibited an average decrease in
      viral potency of 12-fold compared to wild-type virus. Collectively, these results
      suggest that both LdMNPV enhancin genes contribute to viral potency, that each
      enhancin protein can partially compensate for the lack of the other protein, and
      that both enhancin genes are necessary for wild-type viral potency.

PMID- 11507210
TI  - Differential immunogenicity of Epstein-Barr virus latent-cycle proteins for human
      CD4(+) T-helper 1 responses.
AB  - Human CD4(+) T-helper 1 cell responses to Epstein-Barr virus (EBV) infection are
      likely to be important in the maintenance of virus-specific CD8(+) memory and/or
      as antiviral effectors in their own right. The present work has used overlapping
      peptides as stimulators of gamma interferon release (i) to identify CD4(+)
      epitopes within four EBV latent-cycle proteins, i.e., the nuclear antigens EBNA1
      and EBNA3C and the latent membrane proteins LMP1 and LMP2, and (ii) to determine
      the frequency and magnitude of memory responses to these proteins in healthy
      virus carriers. Responses to EBNA1 and EBNA3C epitopes were detected in the
      majority of donors, and in the case of EBNA1, their antigen specificity was
      confirmed by in vitro reactivation and cloning of CD4(+) T cells using protein
      loaded dendritic cell stimulators. By contrast, responses to LMP1 and LMP2
      epitopes were seen much less frequently. EBV latent-cycle proteins therefore
      display a marked hierarchy of immunodominance for CD4(+) T-helper 1 cells (EBNA1,
      EBNA3C >> LMP1, LMP2) which is different from that identified for the same
      proteins with respect to CD8(+)-T-cell responses (EBNA3C > EBNA1 > LMP2 >> LMP1).
      Furthermore, the range of CD4(+) memory T-cell frequencies in peripheral blood of
      healthy virus carriers was noticeably lower and narrower than the corresponding
      range of latent antigen-specific CD8(+)-T-cell frequencies.

PMID- 11507211
TI  - Activation of NF-kappaB by the human herpesvirus 8 chemokine receptor ORF74:
      evidence for a paracrine model of Kaposi's sarcoma pathogenesis.
AB  - Infection with human herpesvirus 8 (HHV-8), also known as Kaposi's sarcoma (KS)
      associated herpesvirus, is necessary for the development of KS. The HHV-8 lytic
      phase gene ORF74 is related to G protein-coupled receptors, particularly
      interleukin-8 (IL-8) receptors. ORF74 activates the inositol
      phosphate/phospholipase C pathway and the downstream mitogen-activated protein
      kinases, JNK/SAPK and p38. We show here that ORF74 also activates NF-kappaB
      independent of ligand when expressed in KS-derived HHV-8-negative endothelial
      cells or primary vascular endothelial cells. NF-kappaB activation was enhanced by
      the chemokine GROalpha, but not by IL-8. Mutation of Val to Asp in the ORF74
      second cytoplasmic loop did not affect ligand-independent signaling activity, but
      it greatly increased the response to GROalpha. ORF74 upregulated the expression
      of NF-kappaB-dependent inflammatory cytokines (RANTES, IL-6, IL-8, and
      granulocyte-macrophage colony-stimulating factor) and adhesion molecules (VCAM-1,
      ICAM-1, and E-selectin). Supernatants from transfected KS cells activated NF
      kappaB signaling in untransfected cells and elicited the chemotaxis of monocytoid
      and T-lymphoid cells. Expression of ORF74 conferred on primary endothelial cells
      a morphology that was strikingly similar to that of spindle cells present in KS
      lesions. Taken together, these data, demonstrating that ORF74 activates NF-kappaB
      and induces the expression of proangiogenic and proinflammatory factors, suggest
      that expression of ORF74 in a minority of cells in KS lesions could influence
      uninfected cells or latently infected cells via autocrine and paracrine
      mechanisms, thereby contributing to KS pathogenesis.

PMID- 11507212
TI  - Genetic control of neuroadapted sindbis virus replication in female mice maps to
      chromosome 2 and associates with paralysis and mortality.
AB  - Neuroadapted Sindbis virus (NSV) infection of mice causes hindlimb paralysis and
      100% mortality in the C57BL/6 mouse strain, while adults of the BALB/cBy mouse
      strain are resistant to fatal encephalomyelitis. Levels of viral RNA are higher
      in the brains of infected C57BL/6 mice than in BALB/cBy mice (D. C. Thach et al.,
      J. Virol. 74:6156-6161, 2000). These phenotypic differences between the two
      strains allowed us to map genetic loci involved in mouse susceptibility to NSV
      and to find relationships between mortality, paralysis, and viral RNA levels.
      Analysis of percent mortality in H2-congenic and F(1) mice suggested that the H2
      locus, sex linkage, and imprinting were not involved in determining
      susceptibility and that resistance was partially dominant over susceptibility.
      Segregation analysis using CXB recombinant inbred (RI) mice indicated that the
      percent mortality was multigenic. Interval mapping detected a suggestive
      quantitative trait locus (QTL) on chromosome 2 near marker D2Mit447. Analysis of
      paralysis in the RI mice detected the same suggestive QTL. Viral RNA level in
      F(1) mice was intermediate. Interval mapping using viral RNA levels in RI mice
      detected a significant QTL near marker D2Mit447 that explained 69% of the genetic
      variance. This QTL was confirmed in F2 mice and was designated as Nsv1. Viral RNA
      level, percent paralyzed, and percent mortality were linearly correlated (r = 0.8
      to 0.9). These results indicate that mortality, paralysis, and viral RNA levels
      are related complex traits and that Nsv1 controls early viral load and determines
      the likelihood of paralysis and death.

PMID- 11507213
TI  - Polymorphisms in HLA class I genes associated with both favorable prognosis of
      human immunodeficiency virus (HIV) type 1 infection and positive cytotoxic T
      lymphocyte responses to ALVAC-HIV recombinant canarypox vaccines.
AB  - Carriers of certain human leukocyte antigen class I alleles show favorable
      prognosis of human immunodeficiency virus type 1 (HIV-1) infection, presumably
      due to effective CD8(+) cytotoxic T-lymphocyte responses, but close relationships
      between class I variants mediating such responses to natural and to vaccine HIV-1
      antigen have not been established. During 6 to 30 months of administration and
      follow-up in trials of ALVAC-HIV recombinant canarypox vaccines, cells from 42%
      of 291 HIV-1-negative vaccinated subjects typed at class I loci responded to an
      HIV-1 protein in a lytic bulk CD8(+) cytotoxic T-lymphocyte assay. By 2 weeks
      after the second dose, higher proportions of vaccinees carrying one of two
      alleles consistently associated with slower progression of natural HIV-1
      infection reacted at least once: B*27 carriers reacted to Gag (64%; odds ratio
      [OR] = 10.3, P = 0.001) and Env (36%; OR = 4.6, P = 0.04), and B*57 carriers
      reacted to Env (44%; OR = 6.6, P < 0.05). By 2 weeks after the third or fourth
      dose, B*27 carriers had responded (two or more reactions) to Gag (33%; OR = 4.4,
      P < 0.05) and B*57 carriers had responded to both Gag (39%; OR = 5.3, P = 0.013)
      and Env (39%; OR = 9.5, P = 0.002). Homozygosity at class I loci, although
      conferring an unfavorable prognosis following natural infection, showed no such
      disadvantage for vaccine response. Individual class I alleles have not previously
      demonstrated such clear and consistent relationship with both the clinical course
      of an infection and cellular immunity to a vaccine against the infectious agent.
      This proof of principle that class I an alleles modulate both processes has
      implications for development of HIV-1 and presumably other vaccines.

PMID- 11507214
TI  - Antiretroviral agents restore Mycobacterium-specific T-cell immune responses and
      facilitate controlling a fatal tuberculosis-like disease in Macaques coinfected
      with simian immunodeficiency virus and Mycobacterium bovis BCG.
AB  - The contribution of immune reconstitution following antiretroviral treatment to
      the prevention or treatment of human immunodeficiency virus-related primary or
      reactivation tuberculosis remains unknown. Macaque models of simian
      immunodeficiency virus-Mycobacterium bovis BCG (SIV/BCG) coinfection were
      employed to determine the extent to which anti-Mycobacterium tuberculosis
      immunity can be restored by antiretroviral therapy. Both SIV-infected macaques
      with active BCG reinfection and naive animals with simultaneous SIV/BCG
      coinfection were evaluated. The suppression of SIV replication by antiretroviral
      treatment resulted in control of the active BCG infection and blocked development
      of the fatal SIV-related tuberculosis-like disease. The resolution of this
      disease coincided with the restoration of BCG purified protein derivative (PPD)
      specific T-cell immune responses. In contrast, macaques similarly coinfected with
      SIV/BCG but not receiving antiretroviral therapy had depressed PPD-specific
      primary and memory T-cell immune responses and died from tuberculosis-like
      disease. These results provide in vivo evidence that the restoration of anti
      mycobacterial immunity by antiretroviral agents can improve the clinical outcome
      of an AIDS virus-related tuberculosis-like disease.

PMID- 11507215
TI  - Microtubule reorganization during herpes simplex virus type 1 infection
      facilitates the nuclear localization of VP22, a major virion tegument protein.
AB  - Full-length VP22 is necessary for efficient spread of herpes simplex virus type 1
      (HSV-1) from cell to cell during the course of productive infection. VP22 is a
      virion phosphoprotein, and its nuclear localization initiates between 5 and 7 h
      postinfection (hpi) during the course of synchronized infection. The goal of this
      study was to determine which features of HSV-1 infection function to regulate the
      translocation of VP22 into the nucleus. We report the following. (i) HSV-1(F)
      induced microtubule rearrangement occurred in infected Vero cells by 13 hpi and
      was characterized by the loss of obvious microtubule organizing centers (MtOCs).
      Reformed MtOCs were detected at 25 hpi. (ii) VP22 was observed in the cytoplasm
      of cells prior to microtubule rearrangement and localized in the nucleus
      following the process. (iii) Stabilization of microtubules by the addition of
      taxol increased the accumulation of VP22 in the cytoplasm either during infection
      or in cells expressing VP22 in the absence of other viral proteins. (iv) While
      VP22 localized to the nuclei of cells treated with the microtubule depolymerizing
      agent nocodazole, either taxol or nocodazole treatment prevented optimal HSV-1(F)
      replication in Vero cells. (v) VP22 migration to the nucleus occurred in the
      presence of phosphonoacetic acid, indicating that viral DNA and true late protein
      synthesis were not required for its translocation. Based on these results, we
      conclude that (iv) microtubule reorganization during HSV-1 infection facilitates
      the nuclear localization of VP22.

PMID- 11507216
TI  - Interactions of the TGB1 protein during cell-to-cell movement of Barley stripe
      mosaic virus.
AB  - We have recently used a green fluorescent protein (GFP) fusion to the gammab
      protein of Barley stripe mosaic virus (BSMV) to monitor cell-to-cell and systemic
      virus movement. The gammab protein is involved in expression of the triple gene
      block (TGB) proteins encoded by RNAbeta but is not essential for cell-to-cell
      movement. The GFP fusion appears not to compromise replication or movement
      substantially, and mutagenesis experiments demonstrated that the three most
      abundant TGB-encoded proteins, betab (TGB1), betac (TGB3), and betad (TGB2), are
      each required for cell-to-cell movement (D. M. Lawrence and A. O. Jackson, Mol.
      Plant Pathol. 2:65-75, 2001). We have now extended these analyses by engineering
      a fusion of GFP to TGB1 to examine the expression and interactions of this
      protein during infection. BSMV derivatives containing the TGB1 fusion were able
      to move from cell to cell and establish local lesions in Chenopodium
      amaranticolor and systemic infections of Nicotiana benthamiana and barley. In
      these hosts, the GFP-TGB1 fusion protein exhibited a temporal pattern of
      expression along the advancing edge of the infection front. Microscopic
      examination of the subcellular localization of the GFP-TGB1 protein indicated an
      association with the endoplasmic reticulum and with plasmodesmata. The
      subcellular localization of the TGB1 protein was altered in infections in which
      site-specific mutations were introduced into the six conserved regions of the
      helicase domain and in mutants unable to express the TGB2 and/or TGB3 proteins.
      These results are compatible with a model suggesting that movement requires
      associations of the TGB1 protein with cytoplasmic membranes that are facilitated
      by the TGB2 and TGB3 proteins.

PMID- 11507217
TI  - Expression and immunogenicity of human immunodeficiency virus type 1 Gag
      expressed by a replication-competent rhabdovirus-based vaccine vector.
AB  - A replication-competent rhabdovirus-based vector expressing human
      immunodeficiency virus type 1 (HIV-1) Gag protein was characterized on human cell
      lines and analyzed for the induction of a cellular immune response in mice. We
      previously described a rabies virus (RV) vaccine strain-based vector expressing
      HIV-1 gp160. The recombinant RV was able to induce strong humoral and cellular
      immune responses against the HIV-1 envelope protein in mice (M. J. Schnell et
      al., Proc. Natl. Acad. Sci. USA 97:3544-3549, 2000; J. P. McGettigan et al., J.
      Virol. 75:4430-4434, 2001). Recent research suggests that the HIV-1 Gag protein
      is another important target for cell-mediated host immune defense. Here we show
      that HIV-1 Gag can efficiently be expressed by RV on both human and nonhuman cell
      lines. Infection of HeLa cells with recombinant RV expressing HIV-1 Gag resulted
      in efficient expression of HIV-1 precursor protein p55 as indicated by both
      immunostaining and Western blotting. Moreover, HIV-1 p24 antigen capture enzyme
      linked immunosorbent assay and electron microscopy showed efficient release of
      HIV-1 virus-like particles in addition to bullet-shaped RV particles in the
      supernatants of the infected cells. To initially screen the immunogenicity of
      this new vaccine vector, BALB/c mice received a single vaccination with the
      recombinant RV expressing HIV-1 Gag. Immunized mice developed a vigorous CD8(+)
      cytotoxic T-lymphocyte response against HIV-1 Gag. In addition, 26.8% of CD8(+) T
      cells from mice immunized with RV expressing HIV-1 Gag produced gamma interferon
      after challenge with a recombinant vaccinia virus expressing HIV-1 Gag. These
      results further confirm and extend the potency of RV-based vectors as a potential
      HIV-1 vaccine.

PMID- 11507218
TI  - Intratumoral spread and increased efficacy of a p53-VP22 fusion protein expressed
      by a recombinant adenovirus.
AB  - In vitro experiments have demonstrated intercellular trafficking of the VP22
      tegument protein of herpes simplex virus type 1 from infected cells to
      neighboring cells, which internalize VP22 and transport it to the nucleus. VP22
      also can mediate intercellular transport of fusion proteins, providing a strategy
      for increasing the distribution of therapeutic proteins in gene therapy.
      Intercellular trafficking of the p53 tumor suppressor protein was demonstrated in
      vitro using a plasmid expressing full-length p53 fused in-frame to full-length
      VP22. The p53-VP22 chimeric protein induced apoptosis both in transfected tumor
      cells and in neighboring cells, resulting in a widespread cytotoxic effect. To
      evaluate the anti-tumor activity of p53-VP22 in vivo, we constructed recombinant
      adenoviruses expressing either wild-type p53 (FTCB) or a p53-VP22 fusion protein
      (FVCB) and compared their effects in p53-resistant tumor cells. In vitro,
      treatment of tumor cells with FVCB resulted in enhanced p53-specific apoptosis
      compared to treatment with equivalent doses of FTCB. However, in normal cells
      there was no difference in the dose-related cytotoxicity of FVCB compared to that
      of FTCB. In vivo, treatment of established tumors with FVCB was more effective
      than equivalent doses of FTCB. The dose-response curve to FVCB was flatter than
      that to FTCB; maximal antitumor responses could be achieved using FVCB at doses 1
      log lower than those obtained with FTCB. Increased antitumor efficacy was
      correlated with increased distribution of p53 protein in FVCB-treated tumors.
      This study is the first demonstration that VP22 can enhance the in vivo
      distribution of therapeutic proteins and improve efficacy in gene therapy.

PMID- 11507219
TI  - Borna disease virus phosphoprotein binds a neurite outgrowth factor,
      amphoterin/HMG-1.
AB  - The Borna disease virus (BDV) p24 phosphoprotein is an abundant protein in BDV
      infected cultured cells and animal brains. Therefore, there is a possibility that
      binding of the p24 protein to cellular factor(s) induces functional alterations
      of infected neural cells in the brain. To identify a cellular protein(s) that
      interacts with BDV p24 protein, we performed far-Western blotting with extracts
      from various cell lines. Using recombinant p24 protein as a probe, we detected a
      30-kDa protein in all cell lines examined. Binding between the 30-kDa and BDV p24
      proteins was also demonstrated using BDV p24 affinity and ion-exchange
      chromatography columns. Microsequence analysis of the purified 30-kDa protein
      revealed that its N terminus showed complete homology with rat amphoterin
      protein, which is a neurite outgrowth factor abundant in the brain during
      development. Mammalian two-hybrid and immunoprecipitation analyses also confirmed
      that amphoterin is a specific target for the p24 protein in vivo. Furthermore, we
      showed that infection by BDV, as well as purified p24 protein in the medium,
      significantly decreased cell process outgrowth of cells grown on laminin,
      indicating the functional inhibition of amphoterin by interaction with the p24
      protein. Immunohistochemical analysis revealed decreased levels of amphoterin
      protein at the leading edges of BDV-infected cells. Moreover, the expression of
      the receptor for advanced glycation end products, of which the extracellular
      moiety is a receptor for amphoterin, was not significantly activated in BDV
      infected cells during the process of extension, suggesting that the secretion of
      amphoterin from the cell surface is inhibited by the binding of the p24 protein.
      These results suggested that BDV infection may cause direct damage in the
      developing brain by inhibiting the function of amphoterin due to binding by the
      p24 phosphoprotein.

PMID- 11507220
TI  - Expression and function of chemokine receptors on human thymocytes: implications
      for infection by human immunodeficiency virus type 1.
AB  - The presence or absence of the receptor CD4 and the coreceptors CCR5 and CXCR4
      restrict the cell tropism of human immunodeficiency virus type 1 (HIV-1). Despite
      the importance of thymic infection by HIV-1, conflicting reports regarding the
      expression of HIV-1 coreceptors on human thymocytes have not been resolved. We
      assayed the expression and function of the major HIV-1 coreceptors, CCR5 and
      CXCR4, as well as CCR4 and CCR7 as controls, on human thymocytes. We detected
      CCR5 on 2.5% of thymocytes, CXCR4 on 53% of the cells, and CCR4 on 16% and CCR7
      on 11% of human thymocytes. Moreover, infection by R5 HIV-1 did not significantly
      induce expression of CCR5. We found that two widely used anti-CCR5 monoclonal
      antibodies cross-reacted with CCR8, which may account for discrepancies among
      published reports of CCR5 expression on primary cells. This cross-reactivity
      could be eliminated by deletion of amino acids 2 through 4 of CCR8. Chemotaxis
      assays showed that SDF-1, which binds CXCR4; MDC, which binds CCR4; and ELC,
      which binds CCR7, mediated significant chemotaxis of thymocytes. In contrast, MIP
      1beta, whose receptor is CCR5, did not induce significant chemotaxis. Our results
      indicate that CXCR4, CCR4, CCR7, and their chemokine ligands may be involved in
      thymocyte migration during development in the thymus. CCR5 and its ligands,
      however, are likely not involved in these processes. Furthermore, the pattern of
      CCR5 and CXCR4 expression that we found may explain the greater susceptibility of
      human thymocytes to infection by HIV-1 isolates capable of using CXCR4 in cell
      entry compared to those that use only CCR5.

PMID- 11507221
TI  - Latency-associated nuclear antigen encoded by Kaposi's sarcoma-associated
      herpesvirus interacts with Tat and activates the long terminal repeat of human
      immunodeficiency virus type 1 in human cells.
AB  - The latency-associated nuclear antigen (LANA) is constitutively expressed in
      cells infected with the Kaposi's sarcoma (KS) herpesvirus (KSHV), also referred
      to as human herpesvirus 8. KSHV is tightly associated with body cavity-based
      lymphomas (BCBLs) in immunocompromised patients infected with human
      immunodeficiency virus (HIV). LANA, encoded by open reading frame 73 of KSHV, is
      one of a small subset of proteins expressed during latent infection and was shown
      to be important in tethering the viral episome to host chromosomes. Additionally,
      it has been shown that LANA can function as a regulator of transcription.
      However, its role in the progression of disease is still being elucidated. Since
      KS is one of the most common AIDS-associated cancers in the United States and
      BCBLs appear predominantly in AIDS patients, we examined whether LANA is able to
      regulate the HIV type 1 (HIV-1) long terminal repeat (LTR). Using luciferase
      based transient transfection assays, we found that LANA was able to transactivate
      the HIV-1 LTR in the human B-cell line BJAB, human monocytic cell line U937, and
      the human embryonic kidney fibroblast cell line 293T. Moreover, we observed that
      the virus-encoded HIV transactivator protein Tat cooperated with LANA in
      activation of the LTR in a dose-response fashion with increasing amounts of LANA.
      Surprisingly, LANA alone was sufficient to transactivate the HIV-1 LTR in BJAB
      cells. In similar assays using a HIV-1 LTR construct with the core enhancer
      elements deleted; the activity of LANA was diminished but not abolished,
      indicating a mechanism which involves the cooperation of the core enhancer
      elements and downstream elements which include Tat. Furthermore, transient
      transfection of an infectious clone of HIV with LANA demonstrated effects similar
      to those seen in the reporter assays based on Western blot analysis of HIV Gag
      polypeptide p24. Interestingly, we also demonstrated that the carboxy terminus of
      LANA associates with Tat in cells and in vitro. These experiments suggest a role
      for LANA in activating the HIV-1 LTR through association with cellular molecules
      targeting the core enhancer elements and Tat and may have important consequences
      in increasing the levels of HIV in infected individuals and, hence, the disease
      state.

PMID- 11507222
TI  - Heparan sulfate glycosaminoglycans are receptors sufficient to mediate the
      initial binding of adenovirus types 2 and 5.
AB  - Cell infection by adenovirus serotypes 2 and 5 (Ad2/5) initiates with the
      attachment of Ad fiber to the coxsackievirus and Ad receptor (CAR) followed by
      alpha(v) integrin-mediated entry. We recently demonstrated that heparan sulfate
      glycosaminoglycans (HS GAGs) expressed on cell surfaces are involved in the
      binding and infection of Ad2/5 (M. C. Dechecchi, A. Tamanini, A. Bonizzato, and
      G. Cabrini, Virology 268:382-390, 2000). The role of HS GAGs was investigated
      using extracellular soluble domain 1 of CAR (sCAR-D1) and heparin as soluble
      receptor analogues of CAR and HS GAGs in A549 and recombinant CHO cell lines with
      differential levels of expression of the two receptors and cultured to various
      densities. Complete inhibition of binding and infection was obtained by
      preincubating Ad2/5 with both heparin (10 microg/ml) and sCAR-D1 (200 microg/ml)
      in A549 cells. Partial inhibition was observed when heparin and sCAR-D1 were
      preincubated separately with Ad. The level of heparin-sensitive [(3)H]Ad2/5
      binding doubled in sparse A549 cells (50 to 70,000 cells/cm(2)) with respect to
      that of cells grown to confluence (200 to 300,000 cells/cm(2)), in parallel with
      increased expression of HS GAGs. [(3)H]Ad2 bound to sparse CAR-negative CHO cells
      expressing HS GAGs (CHO K1). No [(3)H]Ad2 binding was observed in CHO K1 cells
      upon competitive inhibition with heparin and in HS GAG-defective CHO A745, D677,
      and E606 clones. HS-sensitive Ad2 infection was obtained in CAR-negative sparse
      CHO K1 cells but not in CHO A745 cells, which were permissive to infection only
      upon transfection with CAR. These results demonstrate that HS GAGs are sufficient
      to mediate the initial binding of Ad2/5.

PMID- 11507223
TI  - Concerted action of the FasL/Fas and perforin/granzyme A and B pathways is
      mandatory for the development of early viral hepatitis but not for recovery from
      viral infection.
AB  - Cytotoxic T lymphocytes (CTL) play a major role in the recovery from primary
      viral infections and the accompanying tissue injuries. However, it is unclear to
      what extent the two main cytolytic pathways, perforin-granzyme A and B exocytosis
      and Fas ligand (FasL)-Fas interaction, contribute to these processes. Here we
      have employed mouse strains with either spontaneous mutations or targeted gene
      defects in one or more components of either of the two cytolytic pathways to
      analyze the molecular basis of viral clearance and induction of hepatitis during
      lymphocytic choriomeningitis virus infection. Our results reveal that viral
      clearance is solely dependent on perforin but that virus-induced liver damage
      only occurs when both the FasL/Fas and the perforin pathways, including granzymes
      A and B, are simultaneously activated. The finding that development of hepatitis
      but not viral clearance is dependent on the concomitant activation of FasL-Fas
      and perforin-granzymes may be helpful in designing novel strategies to prevent
      hepatic failures during viral infections.

PMID- 11507224
TI  - Interaction with the Epstein-Barr virus helicase targets Zta to DNA replication
      compartments.
AB  - Zta has a dual role in the Epstein-Barr virus (EBV) lytic cycle, acting as a key
      regulator of EBV lytic gene expression and also being essential for lytic viral
      DNA replication. Zta's replication function is mediated in part through
      interactions with the core viral replication proteins. We now show interaction
      between Zta and the helicase (BBLF4) and map the binding region to within amino
      acids (aa) 22 to 86 of the Zta activation domain. In immunofluorescence assays,
      green fluorescent protein (GFP)-tagged BBLF4 localized to the cytoplasm of
      transfected cells. Cotransfection of Zta resulted in translocation of BBLF4-GFP
      into the nucleus indicating interaction between these two proteins. However, Zta
      with a deletion of aa 24 to 86 was unable to mediate nuclear translocation of
      BBLF4-GFP. Results obtained with Zta variants carrying deletions across the aa 24
      to 86 region indicated more than one contact site for BBLF4 within this domain,
      and this was reinforced by the behavior of the four-point mutant Zta
      (m22/26,74/75), which was severely impaired for BBLF4 interaction. Binding of
      BBLF4 to Zta was confirmed using GST affinity assays. In both cotransfection
      replication assays and replication assays performed in EBV-positive P3HR1 cells,
      the Zta (m22/26,74/75) mutant was replication defective. In Zta-transfected D98
      HR1 cells, replication compartments could be detected by immunofluorescence
      staining using anti-BMRF1 monoclonal antibody. Cells transfected with Zta
      variants that were defective for helicase binding still formed replication
      compartments, but Zta was excluded from these compartments. These experiments
      reveal a role for the Zta-helicase interaction in targeting Zta to sites of viral
      DNA replication.

PMID- 11507225
TI  - U(L)31 and U(L)34 proteins of herpes simplex virus type 1 form a complex that
      accumulates at the nuclear rim and is required for envelopment of nucleocapsids.
AB  - The herpes simplex virus type 1 (HSV-1) U(L)34 protein is likely a type II
      membrane protein that localizes within the nuclear membrane and is required for
      efficient envelopment of progeny virions at the nuclear envelope, whereas the
      U(L)31 gene product of HSV-1 is a nuclear matrix-associated phosphoprotein
      previously shown to interact with U(L)34 protein in HSV-1-infected cell lysates.
      For these studies, polyclonal antisera directed against purified fusion proteins
      containing U(L)31 protein fused to glutathione-S-transferase (U(L)31-GST) and
      U(L)34 protein fused to GST (U(L)34-GST) were demonstrated to specifically
      recognize the U(L)31 and U(L)34 proteins of approximately 34,000 and 30,000 Da,
      respectively. The U(L)31 and U(L)34 gene products colocalized in a smooth pattern
      throughout the nuclear rim of infected cells by 10 h postinfection. U(L)34
      protein also accumulated in pleiomorphic cytoplasmic structures at early times
      and associated with an altered nuclear envelope late in infection. Localization
      of U(L)31 protein at the nuclear rim required the presence of U(L)34 protein,
      inasmuch as cells infected with a U(L)34 null mutant virus contained U(L)31
      protein primarily in central intranuclear domains separate from the nuclear rim,
      and to a lesser extent in the cytoplasm. Conversely, localization of U(L)34
      protein exclusively at the nuclear rim required the presence of the U(L)31 gene
      product, inasmuch as U(L)34 protein was detectable at the nuclear rim, in
      replication compartments, and in the cytoplasm of cells infected with a U(L)31
      null virus. When transiently expressed in the absence of other viral factors,
      U(L)31 protein localized diffusely in the nucleoplasm, whereas U(L)34 protein
      localized primarily in the cytoplasm and at the nuclear rim. In contrast,
      coexpression of the U(L)31 and U(L)34 proteins was sufficient to target both
      proteins exclusively to the nuclear rim. The proteins were also shown to directly
      interact in vitro in the absence of other viral proteins. In cells infected with
      a virus lacking the U(S)3-encoded protein kinase, previously shown to
      phosphorylate the U(L)34 gene product, U(L)31 and U(L)34 proteins colocalized in
      small punctate areas that accumulated on the nuclear rim. Thus, U(S)3 kinase is
      required for even distribution of U(L)31 and U(L)34 proteins throughout the
      nuclear rim. Taken together with the similar phenotypes of the U(L)31 and U(L)34
      deletion mutants, these data strongly suggest that the U(L)31 and U(L)34 proteins
      form a complex that accumulates at the nuclear membrane and plays an important
      role in nucleocapsid envelopment at the inner nuclear membrane.

PMID- 11507227
TI  - Tobamovirus replicase coding region is involved in cell-to-cell movement.
AB  - Tobacco mosaic virus (TMV) encodes a 30-kDa movement protein (MP) which enables
      viral movement from cell to cell. It is, however, unclear whether the 126- and
      183-kDa replicase proteins are involved in the cell-to-cell movement of TMV. In
      the course of our studies into TMV-R, a strain with a host range different from
      that of TMV-U1, we have obtained an interesting chimeric virus, UR-hel. The amino
      acid sequence differences between UR-hel and TMV-U1 are located only in the
      helicase-like domain of the replicase. Interestingly, UR-hel has a defect in its
      cell-to-cell movement. The replication of UR-hel showed a level of replication of
      the genome, synthesis, and accumulation of MP similar to that observed in TMV-U1
      inoculated protoplasts. Such observations support the hypothesis that the
      replicase coding region may in some fashion be involved in cell-to-cell movement
      of TMV.

PMID- 11507226
TI  - Fate of the inner nuclear membrane protein lamin B receptor and nuclear lamins in
      herpes simplex virus type 1 infection.
AB  - During herpesvirus egress, capsids bud through the inner nuclear membrane.
      Underlying this membrane is the nuclear lamina, a meshwork of intermediate
      filaments with which it is tightly associated. Details of alterations to the
      lamina and the inner nuclear membrane during infection and the mechanisms
      involved in capsid transport across these structures remain unclear. Here we
      describe the fate of key protein components of the nuclear envelope and lamina
      during herpes simplex virus type 1 (HSV-1) infection. We followed the
      distribution of the inner nuclear membrane protein lamin B receptor (LBR) and
      lamins A and B(2) tagged with green fluorescent protein (GFP) in live infected
      cells. Together with additional results from indirect immunofluorescence, our
      studies reveal major morphologic distortion of nuclear-rim LBR and lamins A/C,
      B(1), and B(2). By 8 h p.i., we also observed a significant redistribution of LBR
      GFP to the endoplasmic reticulum, where it colocalized with a subpopulation of
      cytoplasmic glycoprotein B by immunofluorescence. In addition, analysis by
      fluorescence recovery after photobleaching reveals that LBR-GFP exhibited
      increased diffusional mobility within the nuclear membrane of infected cells.
      This is consistent with the disruption of interactions between LBR and the
      underlying lamina. In addition to studying stably expressed GFP-lamins by
      fluorescence microscopy, we studied endogenous A- and B-type lamins in infected
      cells by Western blotting. Both approaches reveal a loss of lamins associated
      with virus infection. These data indicate major disruption of the nuclear
      envelope and lamina of HSV-1-infected cells and are consistent with a virus
      induced dismantling of the nuclear lamina, possibly in order to gain access to
      the inner nuclear membrane.

PMID- 11507228
TI  - A replication-competent feline leukemia virus, subgroup A (FeLV-A), tagged with
      green fluorescent protein reporter exhibits in vitro biological properties
      similar to those of the parental FeLV-A.
AB  - We previously established that lymphoid tumors could be induced in cats by
      intradermal injection of ecotropic feline leukemia virus (FeLV), subgroup A,
      plasmid DNA. In preparation for in vivo experiments to study the cell-to-cell
      pathway for the spread of the virus from the site of inoculation, the green
      fluorescent protein (GFP) transgene fused to an internal ribosome entry site
      (IRES) was inserted after the last nucleotide of the env gene in the ecotropic
      FeLV-A Rickard (FRA) provirus. The engineered plasmid was transfected into feline
      fibroblast cells for production of viruses and determination of GFP expression.
      The virions produced were highly infectious, and the infected cells could
      continue to mediate strong expression of GFP after long-term propagation in
      culture. Similar to parental virus, the transgene-containing ecotropic virus
      demonstrated recombinogenic activity with endogenous FeLV sequences in feline
      cells to produce polytropic recombinant FeLV subgroup B-like viruses which also
      contained the IRES-GFP transgene in the majority of recombinants. To date, the
      engineered virus has been propagated in cell culture for up to 8 months without
      diminished GFP expression. This is the first report of a replication-competent
      FeLV vector with high-level and stable expression of a transgene.

PMID- 11507229
TI  - Cytopathicity of human immunodeficiency virus type 1 primary isolates depends on
      coreceptor usage and not patient disease status.
AB  - It has been hypothesized that human immunodeficiency virus type 1 (HIV-1) evolves
      toward increased cytopathicity in conjunction with disease progression in
      infected patients. A viral property known to evolve in some but not all patients
      is coreceptor utilization, and it has been shown that a switch in coreceptor
      utilization is sufficient for the development of increased cytopathicity. To test
      the hypothesis that the evolution of other viral properties also contributes to
      accelerating cytopathicity in vivo, we used human lymphoid tissue explants to
      assay the cytopathicity of a panel of primary HIV-1 isolates derived from various
      stages of disease characterized by the presence or absence of changes in
      coreceptor preference. We found no evidence of coreceptor-independent increases
      in cytopathicity in isolates obtained either before coreceptor preference changes
      or from patients who progressed to AIDS despite an absence of coreceptor
      evolution. Instead, the cytopathicity of all HIV-1 isolates was determined solely
      by their coreceptor utilization. These results argue that HIV-1 does not evolve
      toward increased cytopathicity independently of changes in coreceptor
      utilization.

PMID- 11507230
TI  - No selection for CCR5 coreceptor usage during parenteral transmission of
      macrophagetropic syncytium-inducing human immunodeficiency virus type 1.
AB  - In two cases of parenteral transmission of human immunodeficiency virus type 1
      (HIV-1) syncitium-inducing (SI) variants, we previously observed selection for
      macrophagetropic variants. Although infection of macrophages is generally
      mediated via CCR5, we found no selection for SI variants that could use CCR5 as
      coreceptor in addition to CXCR4, suggesting that features other than coreceptor
      usage account for the macrophagetropism of these transmitted SI HIV-1 variants.

PMID- 11507231
TI  - Varicella-zoster virus ORF47 protein serine kinase: characterization of a cloned,
      biologically active phosphotransferase and two viral substrates, ORF62 and ORF63.
AB  - Varicella-zoster virus (VZV) codes for a protein serine kinase called ORF47; the
      herpes simplex virus (HSV) homolog is UL13. No recombinant alphaherpesvirus
      serine kinase has been biologically active in vitro. We discovered that
      preservation of the intrinsic kinase activity of recombinant VZV ORF47 required
      unusually stringent in vitro conditions, including physiological concentrations
      of polyamines. In this assay, ORF47 phosphorylated two VZV regulatory proteins:
      the ORF62 protein (homolog of HSV ICP4) and the ORF63 protein (homolog of HSV
      ICP22). Of interest, ORF47 kinase also coprecipitated ORF63 protein from the
      kinase assay supernatant.

PMID- 11507232
TI  - Peptides corresponding to the heptad repeat motifs in the transmembrane protein
      (gp41) of human immunodeficiency virus type 1 elicit antibodies to receptor
      activated conformations of the envelope glycoprotein.
AB  - Two heptad repeat regions in the ectodomain of the human immunodeficiency virus
      type 1 (HIV-1) transmembrane subunit (gp41) self-assemble into a six-helix bundle
      structure that is critical for virus entry. Immunizations with peptides
      corresponding to these regions generated antibodies specific to the receptor
      activated conformations of gp41.

PMID- 11507233
TI  - Jaagsiekte sheep retrovirus Env protein stabilizes retrovirus vectors against
      inactivation by lung surfactant, centrifugation, and freeze-thaw cycling.
AB  - Jaagsiekte sheep retrovirus (JSRV) replicates in the lungs of sheep and causes
      the secretion of copious lung fluid containing the virus. Adaptation of JSRV to
      infection and replication in the lung and its apparent resistance to the
      denaturing activity of lung fluid suggest that vectors based on JSRV would be
      useful for gene therapy targeted to the lung. We show here that a retrovirus
      vector bearing the JSRV Env is stable during treatment with lung surfactant while
      an otherwise identical vector bearing an amphotropic Env is inactivated.
      Furthermore, the JSRV vector was stable during centrifugation, allowing facile
      vector concentration, and showed no loss of activity after six freeze-thaw
      cycles. However, the JSRV vector was inactivated by standard disinfectants,
      indicating that JSRV vectors pose no unusual safety risk related to their
      improved stability under other conditions.

PMID- 11507234
TI  - Feline immunodeficiency virus-infected cat sera associated with the development
      of broad neutralization resistance in vivo drive similar reversions in vitro.
AB  - We previously reported that, upon reinoculation into cats, a neutralization
      sensitive, tissue culture-adapted strain of feline immunodeficiency virus
      constantly reverted to the broad neutralization resistance typical of primary
      virus isolates and identified residue 481 in the V4 region of the surface
      glycoprotein as a key determinant of the reversion. Here, we found that well
      characterized immune sera, obtained from cats in which such reversion had
      occurred, selected in tissue culture in favor of virus variants that also had a
      neutralization-resistant phenotype and had amino acid 481 changed, thus
      indicating that the host's humoral immune response is capable of driving the
      reversion in the absence of other intervening factors. In contrast, a second
      group of immune sera, elicited by a virus variant that had already reverted to
      neutralization resistance in independent cats, induced the emergence of escape
      mutants lacking broad neutralization resistance and neutralized fewer virus
      variants. It is proposed that the viral variants used to produce the two sets of
      sera may have generated different antibody repertoires.

PMID- 11507235
TI  - Evaluation of the genotoxic effects of the boron neutron capture reaction in
      human melanoma cells using the cytokinesis block micronucleus assay.
AB  - The present work reports on the genotoxicity of the boron neutron capture (BNC)
      reaction in human metastatic melanoma cells (A2058) assessed by the cytokinesis
      block micronucleus assay (CBMN) using p-borono-L-phenylalanine (BPA) as the boron
      delivery agent. Different concentrations of BPA (0.48, 1.2 and 2.4 mM) and
      different fluences of thermal neutrons were studied. Substantial genotoxic
      potential of alpha and lithium particles generated inside or near the malignant
      cell by the BNC reaction was observed in a dose-response manner as measured by
      the frequency of micronucleated binucleated melanoma cells and by the number of
      micronuclei (MN) per binucleated cell. The distribution of the number of MN per
      micronucleated binucleated cell was also studied. The BNC reaction clearly
      modifies this distribution, increasing the frequency of micronucleated cells with
      2 and, especially, > or =3 MN and conversely decreasing the frequency of
      micronucleated cells with 1 MN. A decrease in cell proliferation was also
      observed which correlated with MN formation. A discrete genotoxic and anti
      proliferative contribution from both thermal neutron irradiation and BPA was
      observed and should be considered secondary. Additionally, V79 Chinese hamster
      cells (chromosomal aberrations assay) and human lymphocytes (CBMN assay)
      incubated with different concentrations of BPA alone did not show any evidence of
      genotoxicity. The presented results reinforce the usefulness of the CBMN assay as
      an alternative method for assessment of the deleterious effects induced by high
      LET radiation produced by the BNC reaction in human melanoma cells.

PMID- 11507236
TI  - Lack of change in the levels of liver and kidney cytochrome P-450 isozymes in
      p53+/- knockout mice treated with N-butyl-N-(4-hydroxybutyl)nitrosamine.
AB  - We have previously shown that p53(+/-) knockout mice are highly sensitive to
      urinary bladder carcinogenesis induced by N-butyl-N-(4-hydroxybutyl)nitrosamine
      (BBN) in spite of a lack of effects of p53 heterozygosity on N-butyl-N-(3
      carboxypropyl)nitrosamine (BCPN) excretion in urine. To determine the influence
      of p53 deficiency on in vitro formation of BCPN, mutagenicity of BBN and BCPN and
      levels of several cytochrome P450 (CYP) isozymes, groups of five p53(+/-)
      knockout and wild-type mice (littermates), as well as animals of the C57BL/6
      parental strain, were administered 0.025% BBN in their drinking water for 4
      weeks. The livers and kidneys were then used for analyses of BBN metabolism,
      western immunoblotting and Ames liquid incubation. BBN treatment caused a slight
      decrease in BCPN formation in the livers of C57BL/6 mice, but there was no
      significant difference between p53 knockout, wild-type and C57BL/6 mice. In
      kidney BCPN formation in p53 knockout mice was 33-46% less than that in their
      wild-type counterparts. Using anti-rat CYP antibodies, CYP1A2, 2B9/10, 2E1 and
      3A11/13 were constitutively detected in liver microsomes and CYP2E1 and 3A11/13
      in the kidney. Densitometric determination of these CYP proteins revealed no
      significant variation in levels detected in both tissues among the four groups of
      mice. BBN and BCPN were not mutagenic for Salmonella typhimurium TA100 in either
      the absence or presence of liver S9 from untreated mice and rats and from p53
      knockout mice treated with BBN. In conclusion, p53 deficiency and BBN had no
      enhancing effects on metabolism of BBN to BCPN and expression of the CYP isozymes
      typically responsible for activation of environmental carcinogens, including both
      of the N-nitrosamines tested, and their mutagenicity, indicating that the high
      susceptibility of p53(+/-) knockout mice is not attributable to metabolic
      activation in liver and kidney by CYP isozymes or urinary excretion of BCPN.

PMID- 11507237
TI  - Recombinagenic activity of four compounds in the standard and high bioactivation
      crosses of Drosophila melanogaster in the wing spot test.
AB  - The wing somatic mutation and recombination test (SMART) using Drosophila
      melanogaster was employed to determine the recombinagenic and mutagenic activity
      of four chemicals in an in vivo eukaryotic system. Two different crosses
      involving the wing cell markers mwh and flr(3) were used: the standard cross and
      a high bioactivation cross. The high bioactivation cross is characterized by a
      high constitutive level of cytochromes P450 which leads to an increased
      sensitivity to a number of promutagens and procarcinogens. Three-day-old larvae
      derived from both crosses were treated chronically with the oxidizing agent
      potassium chromate and with the three procarcinogens cyclophosphamide, p
      dimethylaminoazobenzene and 9,10-dimethylanthracene. From both crosses two types
      of progeny were obtained: marker-heterozygous and balancer-heterozygous. The
      wings of both genotypes were analysed for the occurrence of single and twin spots
      expressing the mwh and/or flr(3) mutant phenotypes. In the marker-heterozygous
      genotype the spots can be due either to mitotic recombination or to mutation. In
      contrast, in the balancer-heterozygous genotype only mutational events lead to
      spot formation, all recombination events being eliminated. The oxidizing agent
      potassium chromate was equally and highly genotoxic in both crosses.
      Surprisingly, the promutagen cyclophosphamide also showed equal genotoxicity in
      both crosses, whereas p-dimethylaminoazobenzene was negative in the standard
      cross, but clearly genotoxic in the high bioactivation cross. 9,10
      Dimethylanthracene showed a rather weak genotoxicity in the high bioactivation
      cross. Analyses of the dose-response relationships for mwh clones recorded in the
      two wing genotypes demonstrated that all four compounds are recombinagenic. The
      fraction of all genotoxic events which are due to mitotic recombination ranged
      from 83% (9,10-dimethylanthracene) to 99% (p-dimethylaminoazobenzene). These
      results demonstrate that the wing spot test in Drosophila is most suited to the
      detection of recombinagenic activity of genotoxic chemicals.

PMID- 11507238
TI  - A short low-level exposure to metavanadate during a cell cycle-specific interval
      of time is sufficient to permanently derange the differentiative properties of
      Mel cells.
AB  - Mouse erythroleukemia (Mel) cells have a cell cycle-dependent high sensitivity to
      chemical and physical mutagens. This report shows that a 5 h exposure to 0.1 or
      0.01 microg/ml metavanadate during the initial period of erythroid
      differentiation induction was sufficient to permanently damage the ability of
      treated Mel cells and their progeny to undergo erythroid differentiation, without
      affecting cell viability and proliferation. Conversely, a 5 h pulse of
      metavanadate at 1 or 10 microg/ml inhibited both differentiation and cell
      proliferation. The cell cycle-dependent period of mutagenesis was essential for
      fixation of damage in the cell genome and the progeny of the cells treated with
      0.1 or 0.01 microg/ml metavanadate stably inherited an impaired capacity to
      differentiate. The efficiency of the DNA repair synthesis machinery during the
      specific period of exposure of Mel cells seemed directly involved in damage
      fixation. In fact, the mutagenic effects of a 0.1 microg/ml metavanadate pulse
      was further increased in the presence of 1 mM hydroxyurea, an inhibitor of DNA
      repair synthesis. In contrast, 5 microg/ml vanillin, an antimutagenic agent that
      stimulates repair, completely restored the capacity of progeny of cells treated
      with 0.1 microg/ml metavanadate to complete differentiation. Determination of
      [(3)H]deoxythymidine in acid-insoluble DNA indicated that incorporation was
      stimulated by metavanadate alone and was further increased by metavanadate plus
      vanillin; conversely, incorporation of thymidine was reduced in the presence of
      hydroxyurea. The capacity of metavanadate to permanently damage Mel cell
      erythroid differentiation appeared to depend on the cell cycle-related efficiency
      of the DNA repair systems, activated to correct the induced alteration, rather
      than on a specific concentration.

PMID- 11507239
TI  - Genotoxicity of human breast milk from different countries.
AB  - Dietary and/or environmental factors appear to play a key role in the
      international variations that exist in breast cancer incidence. The genotoxicity
      of breast milk extracts is being examined as a possible indicator of in vivo
      exposure of mammary epithelial cells to DNA-damaging agents. Breast milk samples
      were obtained from the UK (n = 32), a high risk country, and from Hong Kong (n =
      10), India (n = 20) and Singapore (n = 20), countries of lower breast cancer
      incidence. The abilities of breast milk extracts to induce DNA damage detected as
      single-strand breaks (SSBs) in the alkaline Comet assay and to induce micronuclei
      in MCL-5 cells and mutations in Salmonella typhimurium YG1019 were investigated.
      In the Comet assay 18 of 32 (56%) UK samples induced significant increases in DNA
      SSBs compared with 2 of 10 (20%), 5 of 20 (25%) and 8 of 20 (40%) of the samples
      from Hong Kong, India and Singapore, respectively. The proportion of positive
      samples was significantly higher in the UK group than in the combined low breast
      cancer incidence group and significantly higher than in the Indian group (P <
      0.05, Fisher's exact test). In the micronucleus assay 9 of 32 (28%) UK samples
      showed significant activity compared with 0 of 10 (0%), 2 of 20 (10%) and 3 of 20
      (15%) of the samples from Hong Kong, India and Singapore, respectively. Extracts
      of all the aforementioned milk samples were also tested for bacterial
      mutagenicity. Nine of 32 (28%) UK samples induced significant activity with a
      dose-response effect. Although activity was detected in samples from the other
      countries, comparable dose-response data could not be obtained because of a lack
      of material. This pilot study suggests that genotoxic components occur more
      frequently in UK breast milk than in milk from some other countries with a lower
      incidence of cancer. More work is required to confirm these initial findings and
      to examine their relevance to variations in breast cancer incidence.

PMID- 11507240
TI  - Differential chromosome behaviour in mammalian oocytes exposed to the
      tranquilizer diazepam in vitro.
AB  - There are several reports demonstrating that aneugens may preferentially affect
      segregation of particular chromosomes in somatic cells. Much less is known on
      specific susceptibility of individual chromosomes to non-disjunction in mammalian
      meiosis in response to chemical exposures. To explore possible chromosome
      specific behaviour and susceptibility to errors in chromosome segregation in
      mammalian oogenesis we employed spindle immunofluoresecence in combination with
      FISH with chromosome-specific probes to analyse congression of chromosomes X, 8
      and 16 in diazepam (DZ)-treated, meiotically delayed meiosis I oocytes of the
      mouse. Concomitantly, we assessed the susceptibility of homologues to
      precociously segregate prior to anaphase I during DZ-induced meiotic arrest.
      About 50% of all oocytes exposed to 25 microg/ml DZ became meiotically delayed.
      Chromosomes failed to congress at the spindle equator in one-third of these
      meiosis I oocytes. The X chromosome was significantly more often located away
      from the spindle equator as compared with the expected random behaviour.
      Concomitantly, DZ exposure induced untimely segregation of homologous chromosomes
      of the gonosome and the autosomes in meiosis I. This occurred with similar
      frequencies. The observations confirm that DZ perturbs cell cycle progression,
      interferes with chromosome alignment, causes predivision and thus may predispose
      mammalian oocytes to errors in chromosome segregation. For the first time,
      chromosome-specific behaviour is reported in female meiosis in response to
      exposure to an aneugenic chemical.

PMID- 11507241
TI  - Ataxia telangiectasia: G2 checkpoint and chromosomal damage in proliferating
      lymphocytes.
AB  - There is a checkpoint pathway in eukaryotic cells that depends on ATM (ataxia
      telangiectasia mutated) kinase which activates the processes leading to the
      repair of DNA damage and also lengthens the G(2) stage of the cell cycle. In
      cells from ataxia telangiectasia patients, due to their lack of active ATM
      kinase, an increase in chromosomal aberrations and a failure to induce G(2)
      lengthening could be expected. However, the basal G(2) timing in ataxia
      telangiectasia cells was longer than in controls and was further extended after X
      ray irradiation (0.4 Gy), although to a lesser extent than in controls. Moreover,
      in control cells caffeine shortened G(2) and increased chromosomal damage 7-fold,
      while in ataxia telangiectasia cells caffeine only trebled aberration yield
      without shortening G(2). As caffeine is an inhibitor of ATM kinase, these results
      suggest the existence of some redundant ATM-independent checkpoint in G(2) of
      ataxia telangiectasia cells. The differential response to caffeine of ataxia
      telangiectasia and control lymphocytes may be explained by the presence of two
      different subpathways in the G(2) checkpoint: one regulating the processing and
      repair of damaged DNA and the other controlling G(2) timing. While in controls
      both subpathways may be mediated by ATM kinase, in ataxia telangiectasia cells
      caffeine-sensitive ATR kinase and the caffeine-insensitive DNA-PK kinases might
      be responsible for DNA repair and the G(2) delay subpathways, respectively.
      Confirmation of this model in ataxia telangiectasia cells with another cell type
      in which both subpathways are mediated by DNA-PK should define whether a
      metylxanthine such as caffeine may also have an additional direct inhibitory
      effect on DNA repair.

PMID- 11507242
TI  - Induction of micronuclei by a new non-peptidic mimetic farnesyltransferase
      inhibitor RPR-115135: role of gene mutations.
AB  - To investigate the relationship between oncogene activation and induction of
      micronuclei by a new non-peptidic mimetic farnesyltransferase inhibitor, RPR
      115135, two isogenic cell lines, human colon cancer line HCT-116, which harbors a
      K-ras mutation, and spontaneously immortalized human breast epithelial cell line
      MCF-10A, were utilized. HCT-116 cells were transfected with an empty control pCMV
      vector (clone CMV-2) or with a dominant negative mutated p53 transgene (clone Mu
      p53-2) to disrupt p53 function. In both clones RPR-115135 induced a significant
      increase in the frequency of micronucleation at concentrations that did not
      affect cell membrane integrity. RPR-115135 produced a significant increase in the
      ratio of CREST+ to CREST- micronuclei. MCF-10A cells were stably transfected with
      either c-Ha-ras or c-erbB-2 or both H-ras + c-erbB-2. No induction of micronuclei
      was observed. No induction of micronuclei was reported in human lymphocytes and
      in primary spinal cells obtained from 7-day chick embryos. In conclusion, RPR
      115135 acts as an aneugenic agent in a complex manner, dependent upon the
      complement of mutations in cell regulatory genes in tumour cells and this
      activity may be independent of ras genotype.

PMID- 11507244
TI  - Phenobarbital, oxazepam and Wyeth 14,643 cause DNA damage as measured by the
      Comet assay.
AB  - Although phenobarbital, oxazepam and Wyeth 14,643 are carcinogens that do not
      form DNA adducts, they induce mutations in the Big Blue transgenic mouse model.
      The mutations produced by these compounds were predominantly G-->T and G-->C
      transversions that we suspect arose from oxidative damage to DNA. To test this,
      we employed the single cell electrophoresis (Comet) assay that detects alkali
      labile lesions in cells sustaining DNA damage. Human myeloid leukemia K562 cells
      were treated with non-cytotoxic doses of the above compounds for 3 h, then placed
      on slides containing low melting point agarose. Cells were lysed, exposed to
      alkaline buffer, electrophoresed and analyzed by microscopy for the existence of
      DNA damage. Extensive DNA damage, most likely due to the existence of single- and
      double-strand breaks and apurinic/apyrimidinic (AP) sites, was observed in cells
      exposed to oxazepam (1 mM) and Wyeth 14,643 (0.5 mM). On the other hand, damage
      of this sort was not observed in cells exposed to phenobarbital (1 mM). However,
      the addition of S9 liver extracts to cells exposed in the presence of
      phenobarbital resulted in significant amounts of DNA damage. We conclude from
      these studies that two of the three compounds evaluated in this study mediate
      their mutagenic effects through oxidative stress, but that the mechanism of DNA
      damage caused by phenobarbital differs from that elicited by oxazepam and Wyeth
      14,643.

PMID- 11507243
TI  - Mutations induced by 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP) in
      cecum and proximal and distal colon of lacI transgenic rats.
AB  - 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a food-borne mutagen
      and carcinogen that induces tumors of the colon and the prostate gland in male
      rats and of the mammary gland in female rats. In this study we describe the
      frequency and specificity of PhIP-induced mutations in the cecum, proximal colon
      and distal colon of male and female lacI transgenic rats. This is the first
      report of mutational data from discrete regions of the colon. After 61 days of
      treatment with 200 p.p.m. PhIP mixed into the diet, PhIP-induced mutant
      frequencies were elevated 7-fold in the cecum and 14- to 21-fold in the colon of
      male and female rats compared with untreated controls. PhIP-induced mutant
      frequencies increased significantly (overall trend, P < 10(-4)) along the length
      of the colon of both males and females, with cecum < proximal colon < distal
      colon. A total of 754 PhIP mutants (363 male, 391 female) were sequenced to
      provide the mutational spectra for each of the three tissue sections from males
      and females. These mutational spectra consisted predominantly of G:C-->T:A and
      G:C-->C:G transversions and deletions of G:C base pairs. There were no
      significant differences between the mutational spectra with respect to sex or
      position in the colon. Therefore, we surmise that following induction of
      mutations by PhIP in male and female colons, non-mutagenic factors, possibly
      hormonal, preferentially influence the formation of tumors in the colon of male
      rats.

PMID- 11507245
TI  - ATM status confers sensitivity to arsenic cytotoxic effects.
AB  - Arsenic (As), a human carcinogen, represents a worldwide health problem due to
      the high number of people exposed to this element in their drinking water.
      Previously our group has demonstrated that As can impair lymphocyte cell
      proliferation in vitro and in vivo and can increase the level of P53 protein,
      with different responses to these effects between individuals. Recently it has
      been shown that ATM protein, responsible for the autosomal recessive disorder
      ataxia telangiectasia (AT), regulates P53. In this study the induced response of
      P53 was evaluated following exposure to As in human lymphoblastoid cell lines
      normal (+/+), heterozygous (+/-) or homozygous (-/-) for the mutant ATM gene.
      After 24 h As treatment we found a dose-dependent induction of P53 in normal and
      heterozygous cell lines, although differences between cell lines were observed.
      An increase in P21(WAF) protein, a main effector of P53 activation, was also
      observed in the same cell lines. In contrast, neither P53 nor P21 induction was
      detected in homozygous cells. The ATM (+/-) and (-/-) genotypes confer more
      sensitivity to As cytotoxic effects than the normal allelic condition.
      Paradoxically, ATM heterozygous cells were more sensitive to As, leading us to
      propose that this might be related to activation of apoptosis and removal of non
      repairable cells. In contrast, in AT cells in which ATM is absent or mutated
      activation of P53 and its target genes is abrogated, allowing cells to replicate
      with damage in the presence of As, with cell death ensuing by a pathway different
      from P53.

PMID- 11507246
TI  - The micronucleus assay in human exfoliated urothelial cells: application in a
      genotoxicity study of workers exposed to a mineral jelly containing sodium
      nitrite and N-phenyl-1-naphthylamine.
AB  - Exposure to certain chemical agents in occupational settings has been identified
      as carcinogenic to the human bladder. Micronucleus (MN) analysis in exfoliated
      urothelial cells is an interesting method for biomonitoring genetic damage in
      human populations. However, few studies have been performed in an occupational
      context. The aim of this study was to examine whether the occupational use of a
      mineral jelly induced a genotoxic risk for workers employed at a single factory
      producing bearings using the MN test on exfoliated urothelial cells. The
      prevalence of micronucleated exfoliated urothelial cells (MNC) was determined in
      35 female workers with dermal exposure to the jelly and 41 female controls. The
      mean percentage of MNC (expressed as percent cells with MN per 1000 cells scored)
      observed in the exposed worker group was 0.46 +/- 0.11% (range 0-2.8) and in the
      control group 0.14 +/- 0.03% (range 0-0.8). There is a significant job effect (P
      = 0.0018, MANCOVA) on the prevalence of MNC, whereas age and smoking habit had no
      significant effect (P = 0.90 and 0.91, respectively). There is no interaction
      between job and smoking habit (P = 0.4421). Exposure to the mineral jelly
      appeared to be the main factor inducing the increased prevalence of MNC. This may
      be due to the presence of mutagens/carcinogens in the jelly: an aromatic amine, N
      phenyl-1-naphthylamine (CAS no. 90-30-2), which is carcinogenic in mice, or
      sodium nitrite (CAS no. 7632-00-0), which is genotoxic in human cell systems. In
      conclusion, these results suggest that use of the mineral jelly could present a
      genotoxic risk for workers. We think that the MN assay on exfoliated cells could
      be valuable for biological monitoring purposes in occupational contexts as a
      marker of significant exposure to bladder mutagenic/carcinogenic agents.

PMID- 11507290
TI  - Tc-99m mercaptoacetyltriglycine clearance: comparison of camera-assisted methods.
AB  - PURPOSE: To compare the accuracy of three camera-assisted methods for the
      measurement of Tc-99m mercaptoacetyltriglycine (MAG3) clearance. MATERIALS AND
      METHODS: MAG3 renal scintigraphy was performed in 21 adults with different
      degrees of renal function. Posterior views were obtained that included the heart
      and the kidneys in the camera field of view. The syringe for injection was imaged
      before and after injection. Blood samples were drawn 24 and 43 minutes after
      injection and plasma radioactivity was measured. Three camera-assisted techniques
      to measure MAG3 clearance were tested: 1) Biexponential fitting of the left
      ventricular curve, normalized to plasma activity at 24 minutes; 2) calculation of
      clearance by relating the integral of the plasma curve (normalized to plasma
      activity) to the kidney activity using the Rutland-Patlak space method; and 3) a
      regression equation measuring clearance from the percentage of the injected dose
      accumulating in the kidneys during the 1- to 2.5-minute period. The camera
      assisted clearances were compared with the single-sample MAG3 clearances
      calculated using the Russell equation. Linear regression analysis was used to
      measure the correlation between the camera-based methods and the single-sample
      techniques. RESULTS: Correlation with r > 0.900 was found for all three
      techniques. The difference in correlation coefficients between the three methods
      was not significant; however, the regression line of method 3 was significantly
      closer to the line of identity (P = 0.005). CONCLUSION: Method 3 most closely
      fits the line of identity and is probably the most practical because no blood
      sample is needed.

PMID- 11507291
TI  - Tl-201 chloride and Tc-99m MIBI accumulation in lung adenocarcinoma in patients
      with and without distant metastases.
AB  - PURPOSE: The relation between Tl-201 chloride accumulation by the tumor and its
      distant metastatic potential were evaluated in patients with lung adenocarcinoma
      and compared with the same parameters achieved using Tc-99m MIBI. METHODS: Fifty
      six patients with primary lung adenocarcinoma were examined before therapy was
      begun. They were classified according to the radiologic findings and pathologic
      diagnosis into two groups: distant metastases and no distant metastases. All
      patients underwent dual-isotope imaging with Tl-201 chloride and Tc-99m MIBI.
      Regions of interest were placed over the tumor uptake (T) and contralateral
      normal lung tissue (N) areas on one transverse view with clearly defined lesions,
      and the T:N ratio and retention index were calculated. RESULTS: The early and
      delayed T:N ratios and retention index using Tl-201 chloride SPECT in the distant
      metastases group were significantly greater (P < 0.001 to P < 0.05) than were
      those in the no-distant-metastases group. There was no significant correlation
      between the T:N ratio and retention index and distant metastatic potential using
      Tc-99m MIBI SPECT. CONCLUSION: Tl-201 chloride SPECT may be more effective than
      Tc-99m MIBI SPECT for evaluating the distant metastatic potential of primary lung
      adenocarcinoma.

PMID- 11507292
TI  - Scintigraphic evaluation of small pulmonary right-to-left shunt and therapeutic
      effect in pulmonary arteriovenous malformation.
AB  - PURPOSE: Right-to-left shunts of pulmonary arteriovenous malformation (PAVM) can
      be detected and measured by pulmonary perfusion scans using Tc-99m MAA. In PAVM
      with a relatively small right-to-left shunt, however, measurement of the shunt
      ratio may not be reliable. This study re-evaluated pulmonary perfusion scans for
      a small right-to-left shunt of PAVM. METHODS: Tc-99m MAA lung scans were
      performed in five patients with proved PAVM before and after percutaneous
      transcatheter embolization. The right-to-left shunt ratio was calculated and
      extrapulmonary uptake was assessed on total-body images. RESULTS: Lung perfusion
      scans obtained before embolization revealed brain uptake in four patients, and
      the shunt ratio ranged from 4.4% to 22.9%. In two patients with a small single
      PAVM, the shunt ratio was less than 15% before treatment and did not change
      significantly after successful embolotherapy. The brain uptake, which had been
      clearly visible before therapy, disappeared after embolization. Renal uptake was
      seen on pre- and post-therapy scans. CONCLUSIONS: Changes in brain activity
      visible on Tc-99m MAA scans might be a more reliable sign than a decreased shunt
      ratio or a change in renal uptake when evaluating embolization therapy in
      patients with PAVM who have a small right-to-left shunt.

PMID- 11507293
TI  - Abdominal abscesses in patients having surgery: an application of Ga-67
      scintigraphic and computed tomographic scanning.
AB  - PURPOSE: Early detection of occult abscesses is important in patients with
      persistent fever after colorectal surgery. In this study, the authors evaluated
      the relative merits of computed tomographic (CT) and Ga-67 scans in the detection
      of intra-abdominal abscesses in patients who had just undergone colorectal
      surgery. MATERIALS AND METHODS: Thirty-four patients who underwent colorectal
      surgery were enrolled in the study. Ga-67 and CT scans were obtained in all
      patients. Ga-67 scintigraphy was performed 24 hours, and later as needed, after
      the injection of 111 MBq (3 mCi) Ga-67 citrate. RESULTS: Intra-abdominal
      abscesses were diagnosed in 16 of the 34 (47%) patients who had colorectal
      surgery. For CT scans, the overall accuracy, sensitivity, and specificity rates
      were 97.1%, 93.7%, and 100%, respectively. For the Ga-67 scans, the diagnostic
      accuracy, sensitivity, and specificity rates were 91.2%, 100%, and 95.2%,
      respectively. In addition, the whole-body Ga-67 scans successfully detected two
      cases of extra-abdominal infection, one case of pneumonia, and one case of
      cellulitis. CONCLUSIONS: Computed tomographic and Ga-67 scans offer complementary
      information and play an important role in the investigation of sources of
      infection in patients after colorectal surgery.

PMID- 11507295
TI  - Quantitative cerebral blood flow imaging in a patient with the Heidenhain variant
      of Creutzfeldt-Jakob disease.
AB  - PURPOSE: This report describes quantitative SPECT cerebral blood flow (CBF)
      changes in a patient with the confirmed Heidenhain variant of Creutzfeldt-Jakob
      disease. MATERIALS AND METHODS: A 60-year-old man reported visual disturbances,
      including left hemianopsia. An electroencephalogram, magnetic resonance imaging,
      cerebral arteriogram, and quantitative SPECT CBF imaging with Xe-133, with and
      without acetazolamide, were performed. After the patient's death, an autopsy was
      performed. RESULTS: The electroencephalographic findings were nonspecific, those
      of magnetic resonance imaging were normal, and the cerebral arteriogram showed
      minimal atherosclerosis. However, the SPECT scan revealed marked depression of
      perfusion in the parietal and occipital cortices that did not change with the
      administration of acetazolamide. Autopsy results were consistent with CJD.
      CONCLUSIONS: Although there is no consistent pattern of CBF changes that is
      characteristic of Creutzfeldt-Jakob disease, the Heidenhain variant of that
      disease may be an exception. Clinical symptoms include profound changes in
      vision, and the pattern of CBF changes in the patient described here included
      depression of perfusion in areas of primary and associated visual cortex. Also of
      interest is the finding that although other imaging did not reveal an
      abnormality, the CBF changes were marked. In addition, vasoreactivity is poor in
      response to acetazolamide, a finding that occurs only late in other neuronal
      degenerative conditions such as Alzheimer's disease.

PMID- 11507294
TI  - Bone, bone marrow, and MIBI scintigraphic findings in Gaucher's disease "bone
      crisis".
AB  - PURPOSE: The authors report the utility of Tc-99m MIBI imaging in Gaucher's
      disease, which results in the accumulation of glucocerebroside in macrophages.
      Inflated macrophages, or Gaucher's cells, involve the reticuloendothelial organs.
      MATERIALS AND METHODS: A 38-year-old man with type I Gaucher's disease,
      splenectomy, and early bone involvement was examined for a low back "bone
      crisis." He had a history of total left hip replacement. Results of pelvic
      radiographs were normal. Magnetic resonance imaging showed complete infiltration
      of the bone marrow in the lumbar spine and the sacrum. The left iliac bone, the
      sacrum, and the adjacent part of L5 showed heterogeneously decreased uptake on
      bone scintigraphs. Hematopoietic bone marrow was absent in these regions and in
      the left femur. No infection of the prosthesis was revealed with labeled
      granulocytes. RESULTS: Avascular necrosis in the left iliac bone was diagnosed,
      which is a very unusual location. There was no uptake of MIBI in the iliac bones
      or the femurs. CONCLUSION: These findings suggest that MIBI may not be a good
      tool for the evaluation of medullary infiltration by Gaucher's cells.

PMID- 11507296
TI  - Ectopic parathyroid adenomas located at the carotid bifurcation: the role of
      preoperative Tc-99m MIBI scintigraphy and the intraoperative gamma probe
      procedure in surgical treatment planning.
AB  - PURPOSE: The prevalence of ectopic parathyroid adenoma (PA) is relatively low,
      despite some studies in which it has been reported to be as high as 20%. Ectopic
      PA is a frequent cause of surgical failure, and therefore some authors recommend
      preoperative imaging to localize the condition in patients with primary
      hyperparathyroid (HPT) disease before initial surgery. METHODS: Two unusual cases
      of primary HPT caused by an ectopic PA located at the carotid bifurcation are
      reported. The patients were examined before operation using Tc-99m MIBI
      scintigraphy and then underwent radioguided surgery using the intraoperative
      gamma probe technique with injection of a low dose (37 MBq; 1 mCi) of Tc-99m
      MIBI. RESULTS: The first patient had a history of primary HPT and coexisting
      multinodular goiter. She had undergone total thyroidectomy in another center, but
      no enlarged parathyroid gland was found at bilateral neck exploration and serum
      calcium and parathyroid hormone levels remained elevated after intervention. The
      patient was referred to our center. A Tc-99m MIBI scan showed a focus of abnormal
      tracer uptake in the superior left laterocervical region that was thought to be a
      PA. The next day she underwent radioguided surgery and an 18-mm PA located at the
      left carotid bifurcation was easily removed through a 2.5-cm skin incision. The
      second patient was examined in our center before surgery. A neck ultrasound
      showed a multinodular goiter but no enlarged parathyroid glands. A pertechnectate
      MIBI subtraction scan revealed a focus of abnormal Tc-99m MIBI uptake in the
      right superior laterocervical region that was thought to be a PA. One week later,
      at radioguided surgery, a 25-mm PA was identified at the right carotid
      bifurcation and removed successfully. CONCLUSIONS: These data strongly support
      the utility of preoperative imaging with Tc-99m MIBI in patients with primary HPT
      before initial neck exploration with the aim of avoiding surgical failure.
      Furthermore, the intraoperative gamma probe technique seems to be useful to
      reduce surgical trauma and, possibly, complications in patients with ectopic PA.

PMID- 11507297
TI  - A different concept in the application of dacryoscintigraphy.
AB  - PURPOSE: Current dacryoscintigraphy methods have several potential pitfalls, the
      most important of which is the outflow of tears. Another is the difficulty in
      fixing the head with the patient seated. To overcome these difficulties, a new
      method was applied. MATERIALS AND METHODS: The study included 77 persons: 43
      controls and 34 patients with epiphora. Two methods were applied to the two
      groups. In the first, protocol 1 (the current conventional protocol), the patient
      was seated in front of a gamma camera and one drop (50 microl) Tc-99m
      pertechnetate containing 50 to 100 microCi radioactivity was instilled in the
      inferior fornix or outer canthus of the eye and dynamic and static images were
      obtained for approximately 15 to 20 minutes. In the other, protocol 2 (our
      protocol), 100 microCi (10 microl) Tc-99m pertechnetate was instilled in the
      outer canthus of the eye using a micropipette with the patient in the supine
      position under the gamma camera. Dynamic images were taken for only 5 minutes.
      CONCLUSION: The pitfalls and difficulties seen with protocol 1 were lessened to a
      great degree in protocol 2.

PMID- 11507298
TI  - Scintigraphy of an avulsion injury of the rectus femoris muscle.

PMID- 11507299
TI  - Idiopathic avascular necrosis of the scaphoid in a child demonstrated by bone
      scintigraphy.

PMID- 11507300
TI  - A false-negative hepatobiliary scan due to the infected fundal end of a septated
      gallbladder.

PMID- 11507301
TI  - Ga-67 scintigraphy in acute leukemia.

PMID- 11507302
TI  - Primary adrenal lymphoma: a case report.

PMID- 11507303
TI  - F-18 fluorodeoxyglucose positron emission tomography in mesenterial Castleman's
      lymphoma.

PMID- 11507305
TI  - A case of cerebral metastases of unknown origin: utility of F-18 FDG positron
      emission tomography to localize the primary tumor.

PMID- 11507304
TI  - Ga-67-avid massive cellulitis within a chronic lymphedematous limb in a survivor
      of Hodgkin's disease.

PMID- 11507306
TI  - Diagnosis of brain infarction on lung perfusion scintigraphy.

PMID- 11507307
TI  - Dilatation of renal artery distal to stenosis demonstrated using acetazolamide Tc
      99m MAG3 scintigraphy.

PMID- 11507308
TI  - Simultaneous Tc-99m MDP and Ga-67 citrate uptake of benign lymphoid hyperplasia
      in the mastoid region.

PMID- 11507309
TI  - Leiomyosarcoma of the liver detected by high F-18 fluorodeoxyglucose positron
      emission tomographic uptake.

PMID- 11507310
TI  - Scintigraphic evaluation of local recurrence of a primitive neuroectodermal
      tumor.

PMID- 11507311
TI  - Aortoenteric fistula complicating an infected aortic graft: diagnosis by
      leukocyte scintigraphy.

PMID- 11507312
TI  - Dehydration-induced renal dysfunction identified on a bone scan.

PMID- 11507314
TI  - Carbohydrates.

PMID- 11507313
TI  - Intra-arterial injection of Tc-99m mimicking reflex sympathetic dystrophy (RSD).

PMID- 11507320
TI  - Early risk of cardiovascular events after commencing hormone replacement therapy.

PMID- 11507321
TI  - Cholesteryl ester transfer protein, high density lipoprotein and arterial
      disease.
AB  - The reported relationships between cholesteryl ester transfer protein, high
      density lipoproteins and arterial disease are confusing and conflicting. Several
      papers published during the review period add substantially to the evidence base
      regarding the atherogenicity (or anti-atherogenicity) of cholesteryl ester
      transfer protein, although none clearly resolves the continuing conflict. These
      new papers are presented against the backdrop of the previous state of knowledge.

PMID- 11507322
TI  - Endothelial function and coronary artery disease.
AB  - The endothelium produces a number of vasodilator and vasoconstrictor substances
      that not only regulate vasomotor tone, but also the recruitment and activity of
      inflammatory cells and the propensity towards thrombosis. Endothelial vasomotor
      function is a convenient way to assess these other functions, and is related to
      the long-term risk of cardiovascular disease. Lipids (particularly low density
      lipoprotein cholesterol) and oxidant stress play a major role in impairing these
      functions, by reducing the bioavailability of nitric oxide and activating pro
      inflammatory signalling pathways such as nuclear factor kappa B. Biomechanical
      forces on the endothelium, including low shear stress from disturbed blood flow,
      also activate the endothelium increasing vasomotor dysfunction and promoting
      inflammation by upregulating pro-atherogenic genes. In contrast, normal laminar
      shear stress promotes the expression of genes that may protect against
      atherosclerosis. The sub-cellular structure of endothelial cells includes
      caveolae that play an integral part in regulating the activity of endothelial
      nitric oxide synthase. Low density lipoprotein cholesterol and oxidant stress
      impair caveolae structure and function and adversely affect endothelial function.
      Lipid-independent pathways of endothelial cell activation are increasingly
      recognized, and may provide new therapeutic targets. Endothelial
      vasoconstrictors, such as endothelin, antagonize endothelium-derived vasodilators
      and contribute to endothelial dysfunction. Some but not all studies have linked
      certain genetic polymorphisms of the nitric oxide synthase enzyme to vascular
      disease and impaired endothelial function. Such genetic heterogeneity may
      nonetheless offer new insights into the variability of endothelial function.

PMID- 11507323
TI  - Pleiotropic effects of statins: do they matter?
AB  - Treatment with the 3-hydroxy-3-methylglutaryl coenyzme A reductase inhibitors (or
      statins) reduces the risk for cardiovascular events across a broad spectrum of
      patient profiles, as evidenced by both primary prevention and secondary
      prevention trials. Improved survival by way of reduced deaths from coronary heart
      disease was also reported with these agents, which are primarily indicated for
      substantial reduction in LDL-cholesterol levels. However, the statins are
      extremely complex drugs and exhibit a wide variety of vascular effects that may
      or may not be dependent on their lipid-modifying properties. These so-called
      pleiotropic effects include alterations of endothelial function, inflammation,
      coagulation, and plaque stability. The relative contribution of the nonlipid
      effects of statin therapy to the well-documented clinical benefits is currently
      under intense investigation.

PMID- 11507324
TI  - Dietary carbohydrates, physical inactivity, obesity, and the 'metabolic syndrome'
      as predictors of coronary heart disease.
AB  - Several decades of epidemiological and clinical research have identified physical
      inactivity, excessive calorie consumption, and excess weight as common risk
      factors for both type 2 diabetes mellitus and coronary heart disease. This trio
      forms the environmental substrate for a now well-recognized metabolic phenotype
      called the insulin resistance syndrome. Recent data suggest that a high intake of
      rapidly absorbed carbohydrates, which is characterized by a high glycemic load (a
      measure of carbohydrate quality and quantity), may increase the risk of coronary
      heart disease by aggravating glucose intolerance and dyslipidemia. These data
      also suggest that individuals who are obese and insulin resistant are
      particularly prone to the adverse effects of a high dietary glycemic load. In
      addition, data continue to accumulate suggesting the important beneficial effects
      of physical activity, even at moderate levels, and weight reduction on improving
      insulin sensitivity and reducing the risk of coronary heart disease. Future
      metabolic studies should continue to quantify the physiological impact of
      different foods on serum glucose and insulin, and such information should
      routinely be incorporated into large-scale and long-term prospective studies, in
      which the possible interaction effects between diet and other metabolic
      determinants such as physical activity and obesity can be examined. Until more
      definitive data are available, replacing refined grain products and potatoes with
      minimally processed plant-based foods such as whole grains, fruits, and
      vegetables, and reducing the intake of high glycemic load beverages may offer a
      simple strategy for reducing the incidence of coronary heart disease.

PMID- 11507325
TI  - Genetic polymorphisms, lipoproteins and coronary artery disease risk.
AB  - Association studies between gene variants (polymorphisms) and measured
      intermediate phenotypes, such as lipid/lipoprotein levels, or disease endpoints
      such as coronary artery disease, are commonplace in the literature. But have we
      learnt anything from the shortcomings in study design and analytical strategies
      that have resulted in much controversy in this field over the last few years?
      This review highlights some of these problems. Using the lipoprotein lipase gene
      as an example, we evaluate new approaches to identifying polymorphisms that will
      stand up to linkage disequilibrium/association studies with complex disorders in
      this post Human Genome Project age, and emphasize the importance of gene
      environment interaction in assessing the impact of gene variants.

PMID- 11507326
TI  - Oxidants and antioxidants in atherosclerosis.
AB  - The oxidative theory suggests that LDL oxidation contributes to atherogenesis,
      implying that attenuation of this process by antioxidants should decrease
      atherosclerosis. However, a causative link between LDL oxidation and
      atherogenesis is not firmly established. It requires the identification of the
      oxidants that are responsible for the initiation of LDL oxidation, and an
      understanding of the modified moieties that are responsible for the
      proatherogenic activities of oxidized LDL. The present review summarizes recent
      data on potential biological oxidants for LDL in the vessel wall, and discusses
      the antiatherogenic role(s) of selected antioxidants.

PMID- 11507327
TI  - Roles of lectin-like oxidized LDL receptor-1 and its soluble forms in
      atherogenesis.
AB  - Lectin-like oxidized LDL receptor (LOX)-1 is a type II membrane protein that
      belongs to the C-type lectin family of molecules, which can act as a cell-surface
      endocytosis receptor for atherogenic oxidized LDL. LOX-1 can support binding,
      internalization and proteolytic degradation of oxidized LDL, but not of
      significant amounts of acetylated LDL, which is a well-known high-affinity ligand
      for class A scavenger receptors and scavenger receptor expressed by endothelial
      cells (SR-EC). LOX-1 is initially synthesized as a 40-kDa precursor protein with
      N-linked high mannose-type carbohydrate, which is further glycosylated and
      processed into a 50-kDa mature form. LOX-1 expression is not constitutive, but
      can be induced by proinflammatory stimuli, such as tumour necrosis factor-alpha,
      transforming growth factor-beta and bacterial endotoxin, as well as angiotensin
      II, oxidized LDL itself and fluid shear stress. In addition, LOX-1 expression is
      detectable in cultured macrophages and activated vascular smooth muscle cells. In
      vivo, endothelial cells that cover early atherosclerotic lesions, and intimal
      macrophages and smooth muscle cells in advanced atherosclerotic plaques can
      express LOX-1. Cell-surface LOX-1 can be cleaved through some protease activities
      that are associated with the plasma membrane, and released into the culture
      media. Purification of soluble LOX-1 and the N-terminal amino-acid sequencing
      identified the two cleavage sites (Arg86-Ser87 and Lys89-Ser90), both of which
      are located in the membrane proximal extracellular domain of LOX-1. Measurement
      of soluble LOX-1 in vivo may provide a novel diagnostic tool for the evaluation
      and prediction of atherosclerosis and vascular disease.

PMID- 11507328
TI  - Diabetes and other coronary heart disease risk equivalents.
AB  - The close association between diabetes and cardiovascular disease suggests that
      current predictions of a massive increase in the prevalence of type 2 diabetes
      foreshadow an equally daunting rise in the incidence of vascular disease. The
      limited cardiovascular benefits obtained by glucose-lowering treatments, although
      perhaps not surprising, indicate that other cardiovascular risk factors must be
      given serious consideration as therapeutic targets. The impressive reductions in
      the number of vascular events observed in diabetic patients, albeit in small
      patient populations, participating in various drug trials amply justify such an
      approach. A necessary prerequisite, however, is a clear understanding of the
      clinical importance of individual risk factors to the occurrence of vascular
      disease in type 2 diabetic patients. This would appear essential for defining
      treatment strategies in the face of a bewildering array of potential therapeutic
      targets. The present review considers recent studies that have assessed the
      predictive value of risk factors against a diabetic background.

PMID- 11507329
TI  - Soy protein isoflavones, lipids and arterial disease.
AB  - There is convincing evidence that soybean products have beneficial effects on
      cardiovascular disease risk factors. Interest in understanding which components
      of the soybean are responsible for the potential benefits on cardiovascular
      disease risk factors and the magnitude of their effect continues. This review
      focuses on the scientific literature published during 1999-2001, evaluating the
      effects of soy protein isolate, soy foods, and purified isoflavones on plasma
      lipid concentrations and other cardiovascular disease outcomes.

PMID- 11507330
TI  - Nutrition and metabolism.

PMID- 11507331
TI  - Lipid metabolism.

PMID- 11507332
TI  - Hyperlipidaemia and cardiovascular disease.

PMID- 11507333
TI  - Atherosclerosis: cell biology and lipoproteins.

PMID- 11507334
TI  - Therapy and clinical trials.

PMID- 11507335
TI  - Extracellular matrix and wound healing.
AB  - Over the years, most researchers have approached corneal epithelial and stromal
      wound healing as separate events. However, it is becoming increasingly clear that
      even the simplest epithelial debridement wound results in keratocyte death and a
      subsequent stromal response to regenerate the affected area. Thus, the
      interaction between stromal and epithelial healing must be considered to fully
      understand corneal wound healing. Although wound healing has been an active area
      of research for many years, the advent of refractive surgery has stimulated
      research into the regulation of wound repair and provided important insights into
      the molecular components involved in repair. Epithelial and stromal wound healing
      are influenced by extracellular matrix components. The purpose of the current
      article is to review progress in the year 2000 toward understanding mechanisms
      involved in corneal wound healing and how extracellular matrix affects the
      healing processes.

PMID- 11507336
TI  - Corneal neovascularization.
AB  - Corneal neovascularization (NV) is a sight-threatening condition usually
      associated with inflammatory or infectious disorders of the ocular surface. It
      has been shown in the field of cancer angiogenesis research that a balance exists
      between angiogenic factors (such as fibroblast growth factor and vascular
      endothelial growth factor) and anti-angiogenic molecules (such as angiostatin,
      endostatin, or pigment epithelium derived factor) in the cornea. Several
      inflammatory, infectious, degenerative, and traumatic disorders are associated
      with corneal NV, in which the balance is tilted towards angiogenesis. The
      pathogenesis of corneal NV may be influenced by matrix metalloproteinases and
      other proteolytic enzymes. New medical and surgical treatments, including
      angiostatic steroids, nonsteroidal inflammatory agents, argon laser
      photocoagulation, and photodynamic therapy have been effective in animal models
      to inhibit corneal NV and transiently restore corneal "angiogenic privilege."

PMID- 11507337
TI  - Chronic cicatrizing conjunctivitis.
AB  - Conjunctival fibrosis may result from chronic inflammation and may lead to
      alterations of conjunctival architecture. This results in ocular dryness,
      entropion and trichiasis, and corneal complications. Causes of conjunctival
      cicatrization are not limited to autoimmune diseases, such as ocular cicatricial
      pemphigoid, a severe disease associated with poor ocular prognosis. Other well
      known causes include thermal and chemical burns, postinfectious conjunctivitis,
      and Stevens-Johnson syndrome. Ocular rosacea and atopic keratoconjunctivitis
      often are underdiagnosed causes of conjunctival fibrosis. Medical history,
      physical exam, and laboratory tests often allow for diagnosis of the underlying
      disease. Medical management varies according to specific causes, and many
      surgical strategies are available to restore corneal transparency and normal
      palpebral architecture.

PMID- 11507338
TI  - Penetrating keratoplasty in infancy and early childhood.
AB  - Penetrating keratoplasty in infants and young children is performed on an
      infrequent basis. The most common indication is visually significant congenital
      corneal opacity. Surgery must be performed early to avoid amblyopia. Surgical
      techniques differ from those used in adult penetrating keratoplasty because of
      the reduced ocular rigidity encountered in infants and young children. Use of a
      multispecialty team approach is important to improve visual outcome. Poor
      prognostic indicators include bilateral disease, concomitant infantile glaucoma,
      lensectomy and vitrectomy at the time of surgery, previous graft failure,
      extensive goniosynechiae, and extensive corneal vascularization. Prompt
      postoperative optical rehabilitation, combined with occlusion therapy when
      appropriate, is an important determinant of success.

PMID- 11507339
TI  - New lamellar keratoplasty techniques: posterior keratoplasty and deep lamellar
      keratoplasty.
AB  - Posterior keratoplasty is a new surgical technique that may be valuable in
      treating patients with corneal decompensation secondary to endothelial
      dysfunction. There are currently two approaches to posterior keratoplasty. In the
      first approach, a corneal flap is created using a microkeratome (similar to laser
      in situ keratomileusis flap), and posterior stromal tissue is excised (by
      trephination or excimer laser keratectomy). In the second approach, a deep
      stromal pocket is created across the cornea through a superior scleral incision.
      A custom-made flat trephine is inserted into the pocket to excise a posterior
      lamellar disc. Preliminary studies have shown the feasibility of performing these
      techniques in sighted human eyes. Despite potential advantages, further clinical
      studies are needed to determine whether these techniques reduce interface
      scarring, astigmatism and graft rejection, improve visual outcomes, or are
      potentially an alternative for penetrating keratoplasty.

PMID- 11507340
TI  - Amniotic membrane surgery.
AB  - Human amniotic membrane (AM) is composed of three layers: a single epithelial
      layer, a thick basement membrane, and an avascular stroma. Amniotic membrane has
      anti-adhesive properties and is felt to promote epithelialization and decrease
      inflammation, neovascularization, and fibrosis. Amniotic membrane transplantation
      (AMT) is currently being used for a continuously widening spectrum of ophthalmic
      indications. Amniotic membrane transplantation has been shown to be effective in
      the reconstruction of the corneal surface in the setting of persistent epithelial
      defects, sterile corneal ulcerations, and partial limbal stem cell (LSC)
      deficiency states, including those secondary to chemical or thermal burns.
      Amniotic membrane transplantation also has been used in conjunction with limbal
      stem cell transplantation (LSCT) both in a concurrent fashion as well as in
      preparation for LSCT. Amniotic membrane transplantation also has been used in
      place of conjunctival autografting after pterygium excision and to reconstruct
      the conjunctival surface after removal of conjunctival lesions. Most recently, ex
      vivo cultivation and expansion of limbal epithelial cells has been performed
      utilizing AM as a matrix. However, the superiority of AMT over other treatment
      modalities in many of these settings needs to be substantiated by controlled
      clinical trials.

PMID- 11507341
TI  - Keratoprosthesis: an update.
AB  - Porous polytetrafluoroethylene and polyurethane skirt materials, as well as
      copolymers of poly (2-hydroxyethyl methacrylate), have shown promise in
      approaching the goal of a "biointegratable" keratoprosthesis. A novel fixation
      method that uses scleral haptics also has been introduced to increase stability.
      An all silicone device that can be sewn into position has been used successfully,
      temporarily, during vitreoretinal procedures. The prognosis of keratoprosthesis
      (KPro) procedures depends on the preoperative diagnosis: graft failure
      noncicatrizing disease>ocular cicatricial pemphigoid>chemical burns>Stevens
      Johnson syndrome. The likelihood of endophthalmitis after KPro surgery follows
      this scheme. Causative organisms tend to be gram-positive. Modified vitreoretinal
      techniques also have been developed, allowing successful treatment of posterior
      segment complications. The science of keratoprosthesis is advancing more rapidly
      than in previous years. However, use of KPro to address complicated corneal
      blindness worldwide remains limited. The authors conducted an English language
      literature review from January 1, 2000 to April 1, 2001 and describe advances of
      note in the field of keratoprosthesis design, materials, and medical and surgical
      management.

PMID- 11507342
TI  - Excimer laser phototherapeutic keratectomy.
AB  - Excimer laser phototherapeutic keratectomy (PTK) is an important tool in the
      management of superficial corneal pathology. It works well in the treatment of
      anterior corneal dystrophies and degenerations, but we are learning that it may
      have a role in the treatment of certain patients with deeper corneal pathology.
      Indications also are being expanded to treat much less common conditions and also
      to treat children. Irregular astigmatism, which is not treated very well with
      current PTK techniques, may be addressed better with newer approaches, such as
      selective zonal ablation and the use of BioMask. As current PTK techniques are
      improved and newer methods are developed, this procedure will continue to be an
      excellent option for certain patients with superficial corneal problems.

PMID- 11507343
TI  - Wavefront technology in ophthalmology.
AB  - Wavefront sensing is an emerging technology that can measure irregular
      astigmatism as a higher-order wavefront aberration. The application of wavefront
      sensing in ophthalmology might enable the non-invasive observation of living
      retinal cone cells; the measurement of detailed visual function of the central
      nervous system by eliminating higher-order aberrations during examinations by
      adaptive optics; the correction of irregular astigmatism; and the prevention of
      iatrogenic irregular astigmatism induced by conventional refractive surgical
      procedures. In addition, it will be theoretically possible to obtain supernormal
      vision by wavefront-guided refractive surgery.

PMID- 11507344
TI  - Astigmatism management: ablation patterns.
AB  - Treatment of astigmatism is possible with the excimer laser. Results with this
      technology are more predictable and accurate than with incisional techniques.
      Ablation profiles differ for the various types of astigmatism, and the best
      approach is the one in which the least amount of tissue is removed from the
      cornea. Surgical success requires appropriate preoperative counseling, careful
      preoperative measurements, and meticulous intraoperative technique. Reported
      outcomes are excellent and future developments will lead to even better results.

PMID- 11507345
TI  - Hyperopic refractive surgery.
AB  - Although the first attempts at hyperopia correction were made more than 100 years
      ago, it is only in the past several years that the success of hyperopic
      refractive surgery has begun to approach the efficacy of myopia surgery. Corneal
      surgery for the correction of hyperopia includes older lamellar techniques such
      as automated lamellar keratoplasty and epikeratophakia, and more recently
      photorefractive keratectomy and laser in situ keratomileusis. The latter two
      procedures have shown the most success. Using large diameter laser ablations and
      improved keratomes, laser in situ keratomileusis has become a realistic
      alternative for corrections of up to 4 or 5 diopters with astigmatic corrections.
      Laser thermal keratoplasty using the Holmium or diode laser and contact
      techniques also have gained popularity and shown some potential. Collagen
      shrinkage procedures are easy to perform and have relatively few complications,
      but over correction and regression are problems. Crystalline lens surgery and
      phakic intraocular lenses are being investigated actively and are promising;
      however, safety issues persist. The surgical treatments of hyperopia present a
      significant challenge and reward for the ophthalmic surgeon.

PMID- 11507346
TI  - Surgically induced topographical abnormalities after LASIK: management of central
      islands, corneal ectasia, decentration, and irregular astigmatism.
AB  - Proper preoperative evaluation is critical for avoiding many postoperative
      complications associated with laser in-situ keratomileusis (LASIK). Proper
      nonsurgical management includes careful monitoring of patients during the
      recovery period using various testing procedures, including corneal topography.
      When surgical intervention is required, a stepwise approach often is used as a
      conservative treatment, allowing further treatment if necessary. Many
      complications after LASIK are amenable to further treatment. However, it often is
      advisable to monitor patients until improved instrumentation is developed. The
      authors review the etiology and management of several complications after LASIK
      by reviewing the literature and relaying their own clinical experiences.

PMID- 11507347
TI  - Dry eye after refractive surgery.
AB  - Photorefractive keratectomy and laser in situ keratomileusis can induce or
      exacerbate dry eye after surgery. This manifests as an increase in degree and
      frequency of symptoms, corneal findings, such as superficial punctate
      keratopathy, and abnormal results of dry eye tests, such as the Schirmer test and
      tear break-up time. The cause mainly involves decreased corneal sensation,
      resulting in decreased feedback to the lacrimal gland and reduced tear
      production. Other causes may include increased evaporation, inflammation, or
      toxicity of medications. Dry eye may result infrequently in impaired wound
      healing and decreased optical quality of the cornea, but it is transient, lasting
      from a few weeks up to 1 year. Patients should be warned about this distressing
      complication. During a period of dry eye, artificial tears and punctal plugs are
      helpful in preventing or alleviating patient discomfort.

PMID- 11507348
TI  - Laser subepithelial keratomileusis: electron microscopy and visual outcomes of
      flap photorefractive keratectomy.
AB  - Laser epithelial keratomileusis (LASEK) is a surgical technique that may be
      performed in patients with low myopia who are considering conventional
      photorefractive keratectomy (PRK), in patients with thin corneas, and in patients
      with professions or lifestyles that predispose them to trauma. Ethanol (18%) is
      applied for 25 seconds and a hinged epithelial flap is created. After laser
      ablation, the flap is repositioned over the ablated stroma. Our data showed that
      epithelial defects occurred in 63% eyes on Day 1. Postoperative pain was absent
      in 47%. Uncorrected visual acuity of 20/40 or better was achieved in all patients
      at 1 week. Data from several studies suggest that LASEK may reduce postoperative
      pain and corneal haze associated with PRK. LASEK offers the potential advantage
      of avoiding flap-related complications associated with laser in situ
      keratomileusis and decreasing postoperative pain and corneal scarring associated
      with PRK. Long-term studies are needed to confirm these potential advantages and
      to determine the safety, efficacy, and predictability of this surgical technique.

PMID- 11507349
TI  - Acid sensors in the gut: a taste of things to come.
AB  - Physiological pain is mediated by the transduction of nociceptive stimuli via the
      peripheral terminals of nociceptors to the spinal dorsal horn neurones, before
      projection to the cerebral cortex. Pathological states of inflammation and nerve
      injury alter the transduction properties of peripheral nociceptors and spinal
      dorsal horn neurones via post-translational changes induced within receptors/ion
      channels by activation of intracellular transduction cascades. This leads to a
      sensitized system with altered stimulus response characteristics, which manifests
      as a clinical hypersensitivity state. With the recent advances in molecular
      biology it has become possible to identify the various receptors and ion channels
      involved in nociceptive transduction in health and disease. This new insight is
      likely to lead to a more targeted approach towards treating both visceral and
      somatic pain.

PMID- 11507350
TI  - Telomeres and telomerases: intimations of immortality.
AB  - There is a constant balance in cancer cells between division and death. The
      malignant phenotype is associated with a continuing cell cycle or
      'immortalization'. Telomeres, structures that cap the chromosomes, are related to
      cell longevity and are regulated by a ribonucleoprotein called telomerase. This
      review describes the possible roles of telomeres and telomerase in the malignant
      process.

PMID- 11507351
TI  - Increased acid-sensing ion channel ASIC-3 in inflamed human intestine.
AB  - OBJECTIVES: Acid-sensing ion channels (ASICs) are expressed by rat sensory
      neurons and may mediate pain associated with tissue acidosis after inflammation
      or injury. Our aim was to examine the molecular forms and localization of ASICs
      in human intestine and dorsal root ganglia using immunochemical techniques, and
      to measure the effects of inflammation and injury. DESIGN AND METHODS: Inflamed
      Crohn's disease intestine and injured human dorsal root ganglia, with appropriate
      controls, were studied by Western blotting and immunohistochemistry, using
      specific affinity-purified ASIC antibodies. RESULTS: In the Western blot, there
      was a significant three-fold increase in the mean relative optical density of the
      ASIC-3 55-kDa band (but not ASIC-1 or ASIC-2) in full-thickness inflamed
      intestine, as well as in separated muscle and mucosal layers. There was a
      corresponding trend for an increased immunoreactive density and increased number
      of ASIC-3-positive neurons in the myenteric and sub-mucous plexus of inflamed
      intestine. In dorsal root ganglia, immunoreactivity for all ASICs was restricted
      to a sub-population (about 50%) of small-diameter (nociceptor) sensory neurons,
      and was generally less intense after injury. CONCLUSIONS: Increased ASIC-3 in
      inflamed intestine suggests a role in pain or dysmotility, for which ASICs
      represent new therapeutic targets.

PMID- 11507352
TI  - Flow-cytometric detection of lactase expression in normal and coeliac intestinal
      epithelium.
AB  - OBJECTIVE: Enterocyte lactase expression is a useful marker of gluten toxicity.
      In this study, the technique of flow cytometry was evaluated to quantify lactase
      expression in coeliac disease (CD). METHODS: Duodenal enterocyte suspensions were
      obtained from 23 patients with CD, four patients with dermatitis herpetiformis
      (DH), and 33 control subjects. The percentage of enterocytes that reacted with
      anti-lactase monoclonal antibody was determined by flow cytometry. In some
      subjects, organ culture of duodenal biopsies in the presence of various stimuli
      (including gluten fractions) was performed before enterocyte analysis. RESULTS:
      This study demonstrated that lactase expression can be readily investigated semi
      quantitatively using flow cytometry. Moreover, the level of expression correlated
      with the extent of mucosal damage in gluten-sensitive individuals. However, in
      organ culture experiments, lactase expression did not change in the presence of
      gluten or after marked T-cell activation for 48 h. CONCLUSIONS: Measurement of
      enterocyte lactase expression by flow cytometry is a useful adjunctive test in
      the diagnosis and monitoring of gluten-sensitive enteropathy. However, lactase
      expression is not a suitable marker of gluten-induced toxicity in organ culture.

PMID- 11507353
TI  - Telomerase activity and patient survival after surgery for gastric and
      oesophageal cancer.
AB  - OBJECTIVE: The ribonucleoprotein telomerase extends telomeres in cancer cells and
      has been proposed as a prognostic marker for cancer. We measured telomerase
      expression in proximal adenocarcinomas (those arising in the distal oesophagus or
      at the gastro-oesophageal junction) and distal adenocarcinomas (those arising in
      the corpus or antrum of the stomach) of the foregut, and correlated telomerase
      activity with pathological stage and post-operative survival. DESIGN: Surgical
      specimens were collected from patients undergoing resections for gastric and
      oesophageal carcinomas. Haematoxylin and eosin histology provided data on the
      pathological tumour stage and pathological node stage. METHODS: The telomerase
      activity of cancer specimens was determined using the telomeric repeat
      amplification protocol. A single pathologist, blinded to the results of the
      telomerase assays, reviewed all slides of cancers to assign T and N stages.
      RESULTS: The cancers exhibited a wide range of telomerase expression. There was
      no significant difference between the telomerase activity of proximal
      adenocarcinomas (median, 551 U; 95% confidence interval, 154-2394 U; n = 26) and
      distal adenocarcinomas (median, 703 U; 95% confidence interval, 139-1618 U; n =
      20). Distal adenocarcinomas expressing high telomerase activity (greater than the
      median) were significantly more advanced with regard to T stage than distal
      cancers expressing low telomerase levels (less than the median; P = 0.03, Mann
      Whitney test). In distal adenocarcinomas, high telomerase activity was associated
      with poor patient survival (median 3 months) compared to low telomerase activity
      (median survival 22.4 months; P = 0.01, log-rank test). No such differences were
      observed for proximal adenocarcinomas. CONCLUSIONS: There is a difference between
      gastric and oesophageal/gastro-oesophageal junction adenocarcinomas in terms of
      the relationship with telomerase expression and clinico-pathological variables.
      Among patients with distal gastric adenocarcinoma, telomerase activity correlates
      with markers of advanced disease, whereas this relationship does not hold true in
      oesophageal/gastro-oesophageal junction adenocarcinomas. Telomerase activation
      may occur at different stages of the formation of the malignant phenotype in
      these two cancers and may reflect differences in their pathogenesis. Telomerase
      could be a prognostic marker in gastric but not in oesophageal adenocarcinoma.

PMID- 11507354
TI  - No clinical benefit of adding cisapride to pantoprazole for treatment of gastro
      oesophageal reflux disease.
AB  - OBJECTIVE: Although a proton pump inhibitor (PPI) and a prokinetic drug are often
      combined for the medical treatment of gastro-oesophageal reflux disease (GORD),
      there are few well-conducted clinical studies on the efficacy and tolerability of
      this therapy. This study investigates whether pantoprazole plus cisapride leads
      to an additional benefit in comparison to pantoprazole alone. DESIGN AND SETTING:
      Randomized double-blind prospective multicentre study conducted in patients of 33
      hospitals in Ireland, South Africa and the UK. PARTICIPANTS: A total of 350
      intention-to-treat (ITT) patients aged 18 years or older with GORD of grade II
      and III were included in the study. The per-protocol (PP) population comprised
      152 patients in the pantoprazole group and 136 in the pantoprazole plus cisapride
      group. INTERVENTIONS: Patients received either pantoprazole 40 mg once daily or
      pantoprazole 40 mg once daily plus cisapride 20 mg twice daily. Treatment outcome
      was assessed after 4 and 8 weeks. The primary criterion was endoscopically
      confirmed healing after 4 weeks. Additionally, relief of leading symptoms was
      studied. MAIN OUTCOME MEASURES: The prior null hypothesis was no difference in
      healing rates between both treatment groups. RESULTS: After 4 weeks of treatment
      81% and 82%, and after 8 weeks 89% and 90%, of PP patients treated with
      pantoprazole or pantoprazole plus cisapride were healed, respectively. Thus,
      equivalence of the two treatment strategies could be proven. Additionally,
      improvement of symptom relief showed no significant difference between the two
      regimens. In contrast to disease grade at baseline, Helicobacter pylori status
      did not influence the healing rates in our study. Both study medications were
      tolerated well. CONCLUSION: Addition of cisapride to pantoprazole provides no
      further benefit in the treatment of GORD.

PMID- 11507355
TI  - Various durations of a standard regimen (amoxycillin, metronidazole, colloidal
      bismuth sub-citrate for 2 weeks or with additional ranitidine for 1 or 2 weeks)
      on eradication of Helicobacter pylori in Iranian peptic ulcer patients. A
      randomized controlled trial.
AB  - INTRODUCTION: One of the most economical and effective therapeutic regimens for
      eradication of Helicobacter pylori is the classic triple therapy with amoxycillin
      or tetracycline, metronidazole and a bismuth derivative. Addition of H2-receptor
      antagonists to these drugs may heighten the rate of eradication and shorten the
      duration. We therefore performed a randomized controlled trial comparing twice
      daily metronidazole, bismuth derivative and amoxycillin for 2 weeks with
      additional ranitidine for 1 or 2 weeks. PATIENTS AND METHODS: In total, 240 adult
      patients with duodenal ulcer and H. pylori infection were randomly assigned to
      one of the following regimens: (1) amoxycillin 1 g bid, metronidazole 500 mg bid,
      bismuth sub-citrate 240 mg bid and ranitidine 300 mg bid for 1 week; (2) triple
      therapy without ranitidine for 2 weeks; or (3) triple therapy plus ranitidine 300
      mg bid for 2 weeks. Side-effects of the drugs were evaluated two weeks after
      starting the treatment. The rapid urease test and histology from antrum and
      corpus, and/or 14C- urea breath test were used to determine H. pylori eradication
      six weeks after starting the treatment. RESULTS: In total, 195 patients were
      followed up for 6 weeks. The most frequent drug side-effects were unpleasant
      taste (46%), dry mouth (41%) and fatigue (26%), which had an equal distribution
      in all treatment groups. Endoscopy and 14C- urea breath test were performed for
      178 and 123 patients, respectively. Eradication of H. pylori was documented in
      19/64 (29.7%), 29/63 (46%) and 50/68 (73.5%) of patients in groups 1, 2 and 3,
      respectively (P < 0.000001 for group 1 versus group 3; P < 0.0014 for group 2
      versus group 3; difference not significant for group 1 versus group 2). An
      intention-to-treat analysis showed eradication rates of 19/80 (23.75%), 29/80
      (36.25%) and 50/80 (62.5%) for groups 1, 2 and 3, respectively. At four weeks
      post-treatment, the most sensitive test for evaluation of eradication of H.
      pylori was histology. CONCLUSION: Although combined use of an H2-receptor
      antagonist and twice daily triple therapy in a two-week regimen is more effective
      than two-week triple or one-week quadruple therapy in Iranian patients, none of
      these regimens is ideal in countries with a probable high rate of resistant and
      strongly toxic strains of H. pylori.

PMID- 11507357
TI  - Abdominal pain and bowel dysfunction: diagnostic role of intestinal ultrasound.
AB  - BACKGROUND: Abdominal pain and irregular bowel habits are common among young
      people. Irritable bowel syndrome is frequent in the general population and has
      important economic and social costs. Inflammatory bowel diseases are chronic
      processes with an acute or indolent onset in young people. Differential clinical
      diagnosis between irritable bowel syndrome and inflammatory bowel disease can be
      difficult since symptoms and signs are often non-specific. OBJECTIVE: To evaluate
      the role of intestinal ultrasound, a non-invasive, simple and cheap diagnostic
      tool, in the differentiation between organic and functional bowel diseases.
      METHODS: Abdominal and intestinal ultrasound examinations were performed on 313
      consecutive outpatients presenting with abdominal pain and irregular bowel habits
      lasting more than 3 months. These patients had no symptoms or signs indicative of
      organic disorders and no previous diagnosis of organic disease. An intestinal
      wall thickness of more than 7 mm was considered diagnostic for inflammatory bowel
      disease. Subsequently, we compared the ultrasound results with diagnoses obtained
      following the traditional criteria (radiological and endoscopic examinations).
      RESULTS: Intestinal ultrasound for the diagnosis of inflammatory bowel disease
      showed 74% sensitivity, 98% specificity, a positive predictive value of 92% and a
      negative predictive value of 92%. CONCLUSIONS: In our experience, intestinal
      ultrasound seems important as a first diagnostic tool in young patients without
      clear symptoms or signs of organic diseases, and can be used as an indication
      that subsequent invasive tests are required.

PMID- 11507356
TI  - Famotidine versus omeprazole, in combination with amoxycillin and tinidazole, for
      eradication of Helicobacter pylori infection.
AB  - BACKGROUND: Eradication regimens combining two antibiotics with a proton pump
      inhibitor have been studied intensively. In contrast, only a few studies have
      focused on the possible role of H2-receptor antagonists in eradication therapy.
      The mechanism involved in the synergy between antibiotics and proton pump
      inhibitors is still controversial. OBJECTIVES: To compare the results of two
      triple-therapy regimens, different only in the antisecretory drugs used, in
      patients with Helicobacter pylori infection, and to assess the impact of primary
      resistance to metronidazole on treatment outcome. METHODS: A total of 120
      patients with peptic ulcer and non-ulcer dyspepsia were randomly assigned to a 2
      week course of either: famotidine 40 mg twice a day, amoxycillin 1 g twice a day
      and tinidazole 500 mg twice a day (FAT group; n = 60); or omeprazole 20 mg twice
      a day, amoxycillin 1 g twice a day and tinidazole 500 mg twice a day (OAT group;
      n = 60). Upper endoscopy was performed prior to treatment and at least 4 weeks
      after completion of treatment and discontinuation of the antisecretory therapy.
      H. pylori status was assessed by a biopsy urease test, histology and culture.
      RESULTS: In the intention-to-treat analysis, eradication of H. pylori was
      achieved in 48 of the 60 patients (80%; 95% confidence interval: 70-90%) in the
      FAT group, compared to 50 of the 60 patients (83.3%; 95% confidence interval: 74
      93%) in the OAT group. In the per protocol analysis, eradication therapy was
      achieved in 48 out of 53 patients (90.6%; 95% confidence interval: 83-98%)
      treated with FAT and 50 out of 57 patients (87.7%; 95% confidence interval: 79
      96%) treated with OAT (not significant). The primary metronidazole resistance was
      present in 28.8% of strains. Overall, per protocol eradication rates in strains
      resistant and susceptible to metronidazole were 83.3% and 91.3% respectively (P >
      0.05). CONCLUSIONS: Two-week courses of either high-dose famotidine or
      omeprazole, both combined with amoxycillin and tinidazole, are equally effective
      for eradication of H. pylori infection. In a 2-week triple therapy, metronidazole
      resistance has no significant impact on eradication rates.

PMID- 11507358
TI  - The management of irritable bowel syndrome: a European, primary and secondary
      care collaboration.
AB  - OBJECTIVE: To develop recommendations for the diagnosis and management of
      irritable bowel syndrome for European doctors delivering primary care. These
      recommendations can be adapted by local medical groups according to their
      language, custom and health-care systems. METHODS: Twenty-one general
      practitioners and gastroenterologists from Europe attended a workshop planned by
      a steering committee. After a state-of-the-art symposium, four working groups
      considered the following aspects of irritable bowel syndrome management: what to
      tell the patient, diagnosis, non-medical treatment and psychosocial management.
      Current and future drug management was reviewed by the steering committee. The
      resulting recommendations were considered at two plenary sessions during the
      meeting, and by circulation of the material during development of the manuscript.
      RESULTS: The process permitted a unique dialogue between general practitioners
      and gastroenterologists, in which it was necessary to reconcile the specialists'
      emphasis on thoroughness with the practical, epidemiological and economic
      realities of primary care. Despite this dichotomy, consensus was achieved.
      CONCLUSIONS: European general practitioners and gastroenterologists have produced
      recommendations that emphasize education of the patient, a positive symptom-based
      diagnosis, diet and lifestyle advice, psychological support and a critical
      analysis of current specific psychological and pharmacological treatments.

PMID- 11507359
TI  - The effect of a lactose-restricted diet in patients with a positive lactose
      tolerance test, earlier diagnosed as irritable bowel syndrome: a 5-year follow-up
      study.
AB  - DESIGN AND METHODS: Prospectively, the effect of a lactose-restricted diet was
      evaluated among irritable bowel syndrome patients with lactose malabsorption.
      Lactose malabsorption was defined by a positive hydrogen breath test and a
      positive blood-glucose test. An analysis of symptoms was completed before,
      during, 6 weeks after and 5 years after starting the diet. In addition, the
      number of visits made by the patients to the outpatient clinic was scored during
      6 years. RESULTS: In 17 out of 70 irritable bowel syndrome patients (24.3%),
      lactose malabsorption was detected. There was no difference in the symptom score
      between patients with a positive lactose tolerance test and patients with a
      negative lactose tolerance test. After 6 weeks of the lactose-restricted diet,
      symptoms were markedly improved in lactose malabsorption-positive patients (P <
      0.001). After 5 years, one patient was lost for follow-up, and 14 out of the
      remaining 16 lactose malabsorption patients (87.5%) still had no complaints
      during the lactose-restricted diet. Two patients chose not to follow the diet
      continuously and accepted the discomfort caused by lactose intake. Only two out
      of 16 patients (12.5%) no longer experienced any benefit from lactose
      restriction. In the 5 years before their diagnosis of lactose malabsorption,
      these 16 patients visited the outpatient clinic a total of 192 times (mean 2.4
      visits per year per person; range 1-7 visits). In the 5 years after diagnosis,
      they visited the outpatient clinic a total of 45 times (mean 0.6 visits per year
      per person; range 0-6 visits; P < 0.0001). CONCLUSIONS: In a large majority of
      irritable bowel syndrome patients with lactose malabsorption, which was
      previously clinically unrecognized, a lactose-restricted diet improved symptoms
      markedly both in the short term and the long term. Furthermore, visits by all
      patients to the outpatient clinic were reduced by 75%. We conclude that diet
      therapy is extremely cost- and time-saving. Therefore, it is strongly recommended
      that lactose malabsorption, which is easily treatable, is excluded before
      diagnosing irritable bowel syndrome.

PMID- 11507360
TI  - Deoxycholic acid stimulates migration in colon cancer cells.
AB  - BACKGROUND: Deoxycholic acid and other secondary bile acids have long been
      considered tumour promoters in the colon. However, their effect on cell
      migration, known to play an important role in colon carcinogenesis, has not been
      studied so far. OBJECTIVE: To investigate the possible effects of deoxycholic
      acid on colon cancer-cell migration in culture. METHODS: Human colon carcinoma
      cells (Caco-2) were seeded on basement membrane matrix. To evaluate replication
      blocked cell migration, we wounded confluent monolayers of cells with a sterile
      scalpel, and inhibited cell replication with mitomycin C. Immediately after
      wounding, the cells were exposed to 0-100 micromol/l deoxycholic acid. Migration
      over 72 h was monitored using a phase contrast microscope. RESULTS: Replication
      blocked migration was stimulated by deoxycholic acid in a dose-dependent manner,
      with the maximum effect at 20 micromol/l deoxycholic acid. Enhancement of
      migration rate was unaffected by immunoneutralization of transforming growth
      factor beta (a known migration-promoting peptide). However, specific inhibition
      of protein kinase C markedly inhibited deoxycholic acid-induced Caco-2 cell
      migration. CONCLUSION: In addition to its well-established role in the
      enhancement of proliferation, deoxycholic acid also stimulates colon cancer-cell
      migration along the basement membrane matrix. The mechanism of this stimulation
      is likely to involve protein kinase C. Deoxycholic acid-stimulated migration
      might additionally contribute to the tumour-promoting effects of secondary bile
      acids in the colon.

PMID- 11507361
TI  - Elevation of serum cystatin C concentrations in patients with chronic liver
      disease.
AB  - OBJECTIVE: We examined serum cystatin C concentrations in patients to explore the
      possible clinical application of cystatin C as a marker of disease severity in
      cases of chronic liver diseases. METHODS: Serum cystatin C concentrations were
      determined by an enzyme-linked immunosorbent assay kit in 103 patients with
      various chronic liver diseases and compared with concentrations in healthy
      control volunteers. RESULTS: The mean cystatin C concentration was 0.68 +/- 0.03
      mg/l in chronic hepatitis patients, 1.13 +/- 0.09 mg/l in liver cirrhosis
      patients and 1.16 +/- 0.10 mg/l in hepatocellular carcinoma patients, all
      significantly higher than concentrations in the control volunteers (P < 0.0001).
      Significant correlations were observed between cystatin C concentrations and
      total bilirubin levels, albumin levels, platelet levels, type IV collagen levels
      and hyaluronic acid levels. Serum cystatin C concentrations correlated well with
      histological stages despite the lack of correlation with histological grades.
      CONCLUSION: Our results show that serum cystatin C increases with the progression
      of chronic liver disease and that it is a potential marker for liver fibrosis.

PMID- 11507363
TI  - Nitroimidazole-induced chronic hepatitis.
AB  - Drug-induced chronic hepatitis is a rare pathological condition. There is no
      reported case with chronic hepatitis secondary to nitroimidazole use. We report a
      patient who developed nitroimidazole-induced chronic hepatitis following acute
      exacerbation of hepatitis three times after nitroimidazole use.

PMID- 11507362
TI  - Cirrhosis serum induces a nitric oxide-associated vascular hyporeactivity of
      aortic segments from healthy rats in vitro.
AB  - OBJECTIVE: Arterial vasodilation with concomitant hyperdynamic circulation are
      common findings in liver cirrhosis. Nitric oxide acting at a local level has been
      suggested to be pathophysiologically relevant in this context. Several systemic
      factors in conjunction with nitric oxide might interfere with the observed
      phenomena. DESIGN: The study has been designed to demonstrate the influence of
      cirrhotic serum on the nitric oxide system and vascular contractility. METHODS:
      The contractile response of aortic segments from healthy rats was studied in
      vitro after incubation with serum of healthy and cirrhosis-induced rats (1 week,
      2 weeks, 3 weeks and 4 weeks after bile duct ligation). A cumulative dose
      response curve to phenylephrine (10--10-4 mol) was established before and after
      incubation with nitric oxide synthesis blocker N(omega)-nitro-L-arginine, the
      more selective aminoguanidine (nitric oxide synthase [NOS]-2 inhibitor) and W7
      (NOS-3 inhibitor). NOS-2 expression in incubated aortic rings was evaluated by
      Western blot analysis. RESULTS: A 4-hour incubation with serum of cirrhosis
      induced rats reduced the maximum contractile response to phenylephrine to 66.8 +/
      9.1% after 1 week, 50.4 +/- 7.8% after 2 weeks, 43.2 +/- 2.8% after 3 weeks and
      35 +/- 5.2% after 4 weeks of bile duct ligation. This reduction in the
      contractility response to phenylephrine was completely reversed by blocking
      nitric oxide synthesis with N(omega)-nitro-L-arginine and aminoguanidine, but not
      after W7. Incubation with cirrhotic serum induced NOS-2 expression in aortic
      rings. In Western blot analysis, the most intensive signal for NOS-2 protein was
      obtained in rings incubated with serum from rats 3 weeks and 4 weeks after
      induction of cirrhosis. CONCLUSIONS: Cirrhotic serum decreases the contractile
      response to phenylephrine even in an early stage of secondary cirrhosis.
      Reversibility of this effect after nitric oxide synthesis blockade suggests an
      induction of nitric oxide synthesis by systemic factors as a major point in
      vascular hyporeactivity to vasoconstrictors in cirrhosis.

PMID- 11507364
TI  - Metallic cough and pyogenic liver abscess.
AB  - The curious symptom of a metallic cough in association with a pyogenic hepatic
      abscess should heighten awareness of a fistula. We describe a 78-year-old female
      with severe diverticular disease, on long-term steroid treatment for polymyalgia
      rheumatica. She developed a pyogenic liver abscess, treated initially by
      antimicrobial therapy, and subsequently drained by ultrasound and computed
      tomography-guided percutaneous transhepatic pigtail catheterization. This was
      complicated by a fistulous communication between the abscess cavity and the
      bronchus, confirmed by radiology. After repeated attempts at drainage and
      antimicrobial therapy the abscess cavity, including the hepatobronchial fistula,
      resolved.

PMID- 11507365
TI  - Hepatic abscesses complicating injection sclerotherapy of haemorrhoids.
AB  - We report the case of a 50-year-old man who developed a febrile illness four days
      after injection sclerotherapy of his haemorrhoids. The patient increasingly
      became unwell and was eventually found to have multiple hepatic abscesses. He
      made a complete recovery with antibiotic therapy. The importance of educating
      both patients and doctors about this complication is emphasized.

PMID- 11507366
TI  - Non-alcoholic steatohepatitis induced by carbamazepine and variegate porphyria.
AB  - A 42-year-old woman presented with acute bullous skin lesions and angio-oedema
      that had developed 3 months after initiation of treatment with carbamazepine for
      epilepsy. Chromatographic analysis of urinary porphyrins was compatible with
      variegate porphyria. This was manifested initially by neurological symptoms that
      were mistaken for epilepsy and later by cutaneous symptoms also. Histological
      findings excluded hepatic porphyria, but revealed severe fatty changes thought to
      be caused by idiosyncratic metabolism of carbamazepine. While the
      porphyrinogenicity of carbamazepine is well known, the presence of variegate
      porphyria has not been reported. The toxic hepatic effects of the drug on hepatic
      cytochrome P-450, which is involved in haem metabolism, could have aggravated the
      pre-existent porphyria, provoking the onset of skin lesions.

PMID- 11507367
TI  - Treatment of hepatic hydrothorax and reduction of chest tube output with
      octreotide.
AB  - Hepatic hydrothorax is a dreaded complication in patients with liver cirrhosis.
      Placement of chest tubes can alleviate respiratory distress, but patients often
      succumb due to excessive fluid and protein loss via the open drain. Our case
      illustrates that high-dose octreotide can strongly reduce hepatic hydrothorax
      drainage volume. This allows removal of the chest tube, which would otherwise not
      have been possible.

PMID- 11507368
TI  - Successfully resected hepatoblastoma in a young adult with chronic hepatitis B:
      report of a case.
AB  - Hepatoblastoma usually occurs in children, but a few cases have also been
      reported in adults. We report the unusual case of hepatoblastoma in an 18-year
      old adult with chronic hepatitis B. He visited a local hospital with right upper
      abdominal pain. Abdominal ultrasound showed a large mass in the right lobe of his
      liver. He was referred to our hospital and admitted for further examination. At
      admission, liver function tests gave slightly elevated results (aspartate
      aminotransferase (AST) 103 IU/l, alanine aminotransferase (ALT) 63 IU/l). A test
      for hepatitis virus revealed that he was a hepatitis B surface antigen (HBsAg)
      carrier and had experienced seroconversion. His alpha-fetoprotein (AFP) was
      elevated to 1 548 000 IU/ml. Abdominal ultrasound showed a 109 x 96 x 80-mm mass
      with mosaic pattern in the right lobe of the liver and right portal vein
      thrombus. Abdominal computed tomography (CT) demonstrated a large low-density
      mass occupying the right lobe, with some high-density parts that showed
      calcification. From these results, we diagnosed hepatoblastoma in a young adult.
      A right lobectomy was performed. Pathological examination showed a highly
      differentiated hepatoblastoma. Adjuvant chemotherapy was performed with cisplatin
      and pirarubicin. The patient has been well and free of recurrence for 12 months,
      and his AFP level remains almost normal.

PMID- 11507369
TI  - Successful treatment of erectile dysfunction and infertility by venesection in a
      patient with primary haemochromatosis.
AB  - A 36-year-old patient with primary haemochromatosis presented with erectile
      dysfunction. Laboratory findings revealed reduced levels of luteinizing hormone
      (0.4 IU/l; normal range 2-12 IU/l), follicle-stimulating hormone (0.1 IU/l;
      normal range 1-12 IU/l) and testosterone (0.49 microg/l; normal range 2-8.1
      microg/l). We made the diagnosis of secondary hypogonadism due to
      haemochromatosis, which is generally supposed to be irreversible. Due to
      consequent venesection therapy, levels of ferritin and transferrin saturation
      could be normalized, and levels of luteinizing hormone and follicle-stimulating
      hormone increased to normal ranges. Also, testosterone levels became normal and
      remained so without any androgen substitution. The patient subsequently regained
      erectile function and potency. This case underlines the fact that a
      hypogonadotrophic hypogonadism caused by iron overload can be reversed by a
      consequent venesection therapy.

PMID- 11507370
TI  - Rectal lymphoma in ulcerative colitis treated with azathioprine.
AB  - Primary malignant lymphoma of the bowel is a rare complication of inflammatory
      bowel disease. The association of gastrointestinal lymphoma, inflammatory bowel
      disease and prior immunosuppression remains unclear. We report the first case of
      azathioprine-treated ulcerative colitis developing rectal lymphoma.

PMID- 11507371
TI  - Acute upper gastrointestinal haemorrhage and colitis: an unusual presentation of
      Wegener's granulomatosis.
AB  - Wegener's granulomatosis is a rare necrotizing vasculitis usually affecting the
      respiratory tract and kidneys. The aetiology is unknown and it usually occurs in
      patients over the age of 40. Involvement of the gastrointestinal tract in
      Wegener's granulomatosis is relatively rare and usually occurs long after the
      onset of initial symptoms. Acute colitis as a presenting feature of Wegener's
      granulomatosis is very rare with only a few reports in the literature. We
      describe a young woman who presented initially to hospital with gastrointestinal
      features and then developed a severe colitis and severe gastrointestinal
      haemorrhage. This preceded the development of respiratory tract features with
      severe pulmonary haemorrhage, haemoptysis and the development of rapidly
      progressive renal failure and nasal septal perforation. Following treatment with
      intravenous steroids and cyclophosphamide, gastrointestinal symptoms and signs
      improved dramatically, as did her pulmonary disease. She still remains dialysis
      dependent, due to end-stage renal disease secondary to glomerulonephritis.

PMID- 11507372
TI  - Reversible pancreatic duct stricture after a blunt abdominal trauma.
AB  - A 32-year-old man developed acute pancreatitis with a main duct stricture
      resulting from blunt abdominal trauma sustained during a car accident 11 weeks
      before admission. No interventions were performed and unusually, after 3 months'
      follow-up, the pancreatic main duct stricture resolved and the patient remained
      asymptomatic. There are no other reports in the literature demonstrating
      resolution of pancreatic main duct stricture without any endoscopic or surgical
      treatment subsequent to a blunt abdominal trauma.

PMID- 11507373
TI  - Acute granulomatous schistosomal cholecystitis.
AB  - Schistosomal cholecystitis is a rare entity with less than 10 cases described in
      the medical literature [1-3]. It is unclear whether schistosomal eggs deposited
      in the wall of the gallbladder trigger a clinically manifest acute cholecystitis,
      since most of the cases described were also found to have concomitant gallstones.
      Herein, we report a patient who developed acute schistosomal granulomatous
      acalculous cholecystitis. The clinical presentation, chronology of events and
      pathological findings strongly support the association between cholecystitis and
      schistosomal infection.

PMID- 11507374
TI  - Xenon in anesthesia.

PMID- 11507375
TI  - Pollution of the environment and the workplace with anesthetic gases.

PMID- 11507376
TI  - The first clinical experiences with xenon.

PMID- 11507377
TI  - Xenon: uptake and costs.

PMID- 11507378
TI  - Clinical pharmacology of xenon.

PMID- 11507379
TI  - Cardiovascular effects of xenon.

PMID- 11507380
TI  - How does xenon produce anesthesia? A perspective from electrophysiological
      studies.

PMID- 11507381
TI  - Respiratory effects of xenon.

PMID- 11507444
TI  - [Detection of liver metastases using contrast enhanced sonography].

PMID- 11507445
TI  - [Transcranial Doppler imaging: state of the art].
AB  - Initially introduced in the early 1980's, transcranial Doppler followed by
      transcranial Doppler sonography were used in neurosurgical units for management
      and follow-up of intracranial vasospasm in patients with subarachnoid hemorrhage.
      This imaging technique, more sensitive and less invasive than catheter
      angiography, also proved to be of value for diagnosis of intracranial
      atherosclerosis, management of patients with head trauma, and evaluation of
      collateral flow through the circle of Willis. Doppler US would also allow
      prediction of the risk of symptomatic embolic events through monitoring of HITS.
      Evaluation of the middle cerebral arteries during carotid occlusion testing is
      useful for evaluating the need for particular revascularization techniques.
      Finally, Doppler imaging is useful to assess patients with possible brain death.
      A recent advance in Doppler imaging is the ability to provide a three-dimensional
      projection (3D Doppler) of the intracranial arteries enabling improved detection
      and evaluation of stenoses involving the circle of Willis and improved
      characterization of intracranial aneurysms. These new applications benefit from
      the use of US contrast agents and harmonic US imaging.

PMID- 11507446
TI  - [Ultrasound for initial evaluation of post-traumatic renal lesions in children].
AB  - PURPOSE: To describe the findings and limitations of color doppler ultrasound
      (CDUS) compared to enhanced CT in the evaluation of pediatric renal trauma and to
      determine the indications for first line imaging work up. PATIENTS AND METHODS:
      17 children (9 girls) aged 3 to 18 years were shown to have one or multiple post
      traumatic renal lesions. All renal lesions were unilateral. All children
      presented with hematuria (microscopic (n=8), gross (n=7), not specified (n=2)).
      16 had CDUS and enhanced CT (gold standard). A 13-year old girl had been imaged
      by both CDUS and IVU. RESULTS: No correlation between the degree of hematuria and
      the severity of renal lesion could be found. Final diagnosis was: fracture with
      uro-hematoma (n=6), contusion (n=5), pedicular lesion (n=2), clotted ureter
      (n=1), intra cystic hemorrhage (n=1), subcapsular hematoma (n=1), urinoma with no
      evidence of fracture (n=1), extra-urinary lesion (n=7). In four cases, CDUS was
      abnormal but the diagnosis of fracture had not been made. In 3 cases, a uro
      hematoma was present and CDUS misdiagnosed a pedicular lesion. CONCLUSION:
      Imaging strategy should not rely on the type of hematuria. Presence of a urinoma
      alters the sensitivity of CDUS. When performed in ideal conditions, a
      comprehensive normal CDUS examination is probably sufficient to exclude a major
      renal injury.

PMID- 11507447
TI  - [Ischemic orchiditis: review of 5 cases diagnosed by color Doppler
      ultrasonography].
AB  - PURPOSE: To study color-doppler ultrasoundfeatures of testicular infarction
      caused by orchiepididymitis, a severe complication of orchiepididymitis.
      MATERIAL: and Methods. Five patients were included over a 2 year period. All
      presented with more than 24 hours of pain. A final diagnosis of testicular
      infarction caused by orchiepididymitis and color doppler ultrasound was available
      in all cases. RESULTS: All patients showed doppler ultrasound signs of testicular
      ischemia. Either vascularisation was not detectable or intratesticular resistive
      index was increased with a negative diastolic flow. Orchidectomy was performed in
      all patients. CONCLUSION: Color doppler examination of the scrotum should include
      measurement of intratesticular resistive index. An elevated RI can be suggestive
      of ischemia.

PMID- 11507448
TI  - [Uterine Doppler study for pre-implantation prognosis of the embryo].
AB  - To assess if a simple US criteria was present allowing pre- and post-implantation
      evaluation of the quality of the embryo. Measurement of the pulsatility index
      (PI) of the uterine arteries in association with evaluation of the type of curves
      was useful for follow-up. PI correlates with the number of follicules, the number
      of cells at Day 2, and the likelihood of pregnancy whereas the type of curve
      directly correlates with the appearance of the oocytes and embryo before the
      transfer. These results should be confirmed by larger studies but they could lead
      to early detection and a treatment of these abnormalities of vascularization.

PMID- 11507449
TI  - [Incidental detection of a rare liver tumor: angiomyolipoma].
AB  - We report the case of a woman who presented a single liver lesion with no
      evidence of specific findings at Doppler US, CT, nuclear studies and MRI to
      suggest angiomyolipoma. The final diagnosis was confirmed at anatomopathology and
      immunohistochemistry which demonstrated positive anti-HMB 45 aspect.

PMID- 11507450
TI  - [Heterotopic pregnancy: value of transabdominal sonography].
AB  - The authors report a case of an heterotopic pregnancy where the transabdominal US
      was more useful than endovaginal US. The embryon in this case was located in
      upper zone of the right iliac fossa, inaccessible to endovaginal US. Both methods
      are complementary.

PMID- 11507451
TI  - [Mediterranean lymphoma mimicking Crohn's disease].
AB  - We report an uncommon localization of mediterranean lymphoma of the terminal
      ileum in a 28 year-old male patient. Ultrasound and Computed Tomography showed
      moderate regular and symmetrical intestinal wall thickening simulating Crohn's
      disease. We highlight the role of computed tomography in the diagnosis, staging
      and detection of complications.

PMID- 11507452
TI  - Clinic and histopathologic study of paradental cysts.

PMID- 11507453
TI  - HLA-DR and intercelular adhesion molecula-1 (ICAM-1) expression in oral lichen
      planus. 

PMID- 11507454
TI  - Importance of predisposing factors in oral candidosis. 

PMID- 11507455
TI  - Burning mouth syndrome: concepts review and update. 

PMID- 11507457
TI  - Intraoral sialadenoma papilliferum. A new clinical case and review of the
      literature.

PMID- 11507456
TI  - Introduction of paracoccidioidomycosis into Spain by a galician retorne from
      Venezuela. 

PMID- 11507458
TI  - Metastatic malignant melanoma of intraparotid lymph nodes. 

PMID- 11507459
TI  - Actinomyces and Candida albicans in periapical lesions. 

PMID- 11507460
TI  - Diagnostic efficacy of fine needle aspiration in salivary gland lesions. 

PMID- 11507461
TI  - Non odontogenic tumors of the jaws: classification. behavior and diagnosis. 

PMID- 11507462
TI  - Odontogenic tumors: classification. clinical features. diagnosis and treatment. 

PMID- 11507463
TI  - Oral actinomicosys in a HIV-1 positive patient. 

PMID- 11507464
TI  - Oral nodular fascitis. 

PMID- 11507465
TI  - Typical trigeminal neuralgia associated with posterior cerebellopontine angle.
      Report of two cases. 

PMID- 11507467
TI  - Histopathologic study of costochondral graft with overgrowth functioning as
      mandibular condyle. 

PMID- 11507466
TI  - Basaloid squamous cell carcinoma of the upper aerodigestive tract. 

PMID- 11507468
TI  - Methods for the diagnosis of salivary gland disorders. 

PMID- 11507469
TI  - Rheumatoid arthritis and temporomandibular joint involvement : a literature
      review. 

PMID- 11507470
TI  - Gingival tuberculosis associated with oral candidosis in a HIV- positive patient.

PMID- 11507471
TI  - Adenomatoid odontogenic tumor in the maxilla. 

PMID- 11507472
TI  - Intramucosal gingival giant nevus. Optical - ultraestructural study of one case. 

PMID- 11507473
TI  - Angular cheilitis in HIV-infected patients from Spain: a common Candida
      associated oral lesion. 

PMID- 11507474
TI  - Hepatitis C virus. Implications in Odontology. 

PMID- 11507475
TI  - Odontogenic maxillary cyst. Clinicopathologic. diagnostic and therapeutic
      considerations. 

PMID- 11507476
TI  - Giant aneurysmal bone cyst of the mandible. 

PMID- 11507477
TI  - Granular cell tumor. Report of a case of rare location. 

PMID- 11507478
TI  - Magnetic resonance imaging in the diagnosis of parotid pleomorphic adenomas. 

PMID- 11507479
TI  - P53 suppressor gene overexpression in oral cancer. 

PMID- 11507480
TI  - Prevention of bacterial endocarditis in dentistry. An update. 

PMID- 11507481
TI  - Pleomorfic adenoma arising in heterotopic salivary gland tisue. 

PMID- 11507482
TI  - Non-Hodgkin's lymphoma presenting as an oral ulceration in an HIV negative
      patient. 

PMID- 11507483
TI  - Lung adenocarcinoma presenting as an oral metastasis. 

PMID- 11507484
TI  - Malignant tumors of teh minor salivary glands. A retrospective study of 89 cases.

PMID- 11507485
TI  - Antifungal drugs in the management of mycosis. 

PMID- 11507487
TI  - Submental epidermoid cyst. A case report with an unusual clinical and
      roentgenological presentation. 

PMID- 11507486
TI  - Paracoccidioidomicosis: report of a case treated with fluconazole. 

PMID- 11507488
TI  - The central (intraosseus) epithelial odontogenic ghost cell tumor: Report of a
      case. 

PMID- 11507489
TI  - Neurofibroma of the alveolar mucosa. Report of a case. 

PMID- 11507490
TI  - Basaloid cell carcinoma. Case report. 

PMID- 11507491
TI  - Prevention and management of radiotherapy complications in patients with head and
      neck tumors. 

PMID- 11507493
TI  - Cherubism: a study of three generations. 

PMID- 11507492
TI  - Pathological malignancy grading and prognosis of head and neck cancer. 

PMID- 11507494
TI  - Acoustic neuroma presenting as orofacial anethesia. 

PMID- 11507495
TI  - Fibrous dysplasia of the jaws. Report of seven cases. 

PMID- 11507496
TI  - Oral lesions associated to human immunodeficiency virus infection in a series of
      510 patients. 

PMID- 11507497
TI  - The role of radiotherapy in the management of salivary gland neoplasms. 

PMID- 11507498
TI  - Dental care of patients with human immunodeficiency virus infection. 

PMID- 11507499
TI  - Giant lip angioma embolized with Ethibloc: a clinical and histologic study.

PMID- 11507500
TI  - Extreme phenytoin-induced gingival hyperplasia. Presentation of two cases. 

PMID- 11507501
TI  - Mandibular pain as a consequence of atlas osteochondroma. 

PMID- 11507502
TI  - Clinicopathological characteristics of inflamed dentigerous cysts. 

PMID- 11507503
TI  - Oral manifestations of HIV infection in Argentina: a study of 1.889 cases.

PMID- 11507504
TI  - Diagnosis and treatment of facial palsy. 

PMID- 11507505
TI  - The fibrous hyperplasia of the maxillary tuberosities.

PMID- 11507507
TI  - CD4 / CD8 T lymphocyte ratio and major histocompatibility complex (MHC)
      expression in lesions among human immunodeficiency (HIV) seropositive and
      seronegative individuals with periodontal disease. 

PMID- 11507506
TI  - Maxillary non-Hodgkin lymphoma. A report of two clinical cases and review of the
      literature.

PMID- 11507508
TI  - Buccal and cervicofacial cellulitis. Concept. pathogenesis. clinical
      manifestations. diagnosis and management.

PMID- 11507509
TI  - Dentin dysplasia. 

PMID- 11507510
TI  - Ameloblastic Fibroma in a patient with Neurofibromatosis.

PMID- 11507511
TI  - Ectomesenchymal chondromyxoid tumor of the tongue.

PMID- 11507513
TI  - Refractary autoimmune thrombocytopenic purpura.

PMID- 11507512
TI  - Mucosal lesions in focal dermal hypoplasia syndrome.

PMID- 11507514
TI  - Detection of human papillomavirus (HPV) DNA using in situ hybridization in oral
      lichen planus. 

PMID- 11507515
TI  - Paraglandular ancient schwannoma. 

PMID- 11507516
TI  - Peripheral T-cell lymphoma in the canine space: presentation of a case and review
      of the literature.

PMID- 11507517
TI  - Squamous cell carcinoma of the oral cavity and Fanconi's anemia. An association
      to bear in mind. 

PMID- 11507518
TI  - Evidence of hiperparathyroidism in a prehistoric mandible. 

PMID- 11507519
TI  - Central odontogenic fibroma: a review of the literature and report of a new case.

PMID- 11507520
TI  - Oral lesions in UK patients with or liable to HIV disease-ten years experience. 

PMID- 11507521
TI  - Prevalence of oral manifestations associated with human immunodeficiency virus
      infection in a homosexuals population. 

PMID- 11507522
TI  - The dental patient with hemostatic disorders. A review of hemostasia
      physiopathology for dental professionals. 

PMID- 11507523
TI  - White sponge nevus: presentation of sixteen cases corresponding to six families. 

PMID- 11507524
TI  - Fine-needle aspiration biopsy (FNAB) in salivary gland lesions. 

PMID- 11507525
TI  - Bullous diseases of the oral mucosa. clinical histological and imnunological
      differential characteristics.

PMID- 11507526
TI  - Drug induced blood coagulation disorders. 

PMID- 11507527
TI  - Maxillary pseudocysts. 

PMID- 11507528
TI  - Oral and maxillofacial metastases of neoplams from other sites of the body. 

PMID- 11507529
TI  - Precancerous lesions of the oral cavity. 

PMID- 11507530
TI  - Langerhans cell histiocytosis: clinical diagnostic features and current concepts.

PMID- 11507531
TI  - Unusual clinical forms of south american blastomycosis. Report of two new cases.

PMID- 11507532
TI  - Glomus tumour of the palate. Diagnostic and treatment.

PMID- 11507533
TI  - Intraoral lesion by gunshot. Diagnostic and treatment.

PMID- 11507534
TI  - Ansiety as an etiologic factor in oral lichen planus. 

PMID- 11507535
TI  - Expression of intercellular adhesion molecule 1 (ICAM-1) in oral squamous cell
      carcinoma. 

PMID- 11507536
TI  - Adhesion molecules and their implication in the immune response to oral cancer. 

PMID- 11507537
TI  - Primary amyloidosis with severe macroglosia. 

PMID- 11507538
TI  - Cleidocranial dysostosis. Report of a case. 

PMID- 11507539
TI  - Spindle cell carcinoma of the oral cavity. Report o f a case. 

PMID- 11507540
TI  - Salivary ductal mega-calculus. 

PMID- 11507541
TI  - The influence of different risk behaviors in the appearance of oral candidiasis
      in aids patients. 

PMID- 11507543
TI  - Cervical adenopathies in Oncology. Clinical presentation. diagnosis and
      treatment. 

PMID- 11507542
TI  - Mesiodens: a retrospective study of 44 patients. 

PMID- 11507544
TI  - Trigeminal autonomic headache. 

PMID- 11507545
TI  - Dental manifestations of systemic disease. 

PMID- 11507546
TI  - Giant cavernous angioma of the head and neck. A case report. 

PMID- 11507547
TI  - Angioneurotic edema caused by ACEI: a case report. 

PMID- 11507548
TI  - Maxillofacial neurilemmomas. A report of three cases. 

PMID- 11507549
TI  - Clinical and histopathological description of a new case of vigabatrin-induced
      gingival overgrowth. 

PMID- 11507550
TI  - Prevalence of Porphyromonas gingivalis. Prevotella intermedia and Actinobacillus
      actinomycetemcomitans in patients with rapidly progressive periodontitis. 

PMID- 11507551
TI  - Glandular odontogenic cyst. A retrospective clinical. radiographic and
      histological study. 

PMID- 11507552
TI  - The corners of the mouth as a site for pathology. 

PMID- 11507553
TI  - Maxillofacial alterations in a family with pycnodysostosis. 

PMID- 11507554
TI  - Pathology of the oral mucosa in the Spanish institutionalized elderly. 

PMID- 11507555
TI  - Quantitative analysis of saliva in patients with oral lichen planus: a study of
      100 cases. 

PMID- 11507556
TI  - Oral manifestations in pediatric patients with oncologic pathologic. 

PMID- 11507557
TI  - The efficacy of diagnostic procedures in medical-surgical pathology of the
      salivary glands. 

PMID- 11507558
TI  - Primary hyperparathyroidism. Presenting as brown tumors in the maxilla. 208.

PMID- 11507559
TI  - Discoid lupus erythematosus with chronic desquamative gingivitis. A case report
      and.

PMID- 11507561
TI  - Mandibular infected buccal cyst. A case report. 

PMID- 11507562
TI  - Ameloblastoma in Latin America. Analysis of 338 cases. 

PMID- 11507560
TI  - Biochemical alterations and their clinical correlation to oral lichen planus. 

PMID- 11507563
TI  - Oral manifestations associated with elastic pseudoxanthoma. 

PMID- 11507564
TI  - How to make effective posters. 

PMID- 11507565
TI  - Bone marrow transplant complications. Chronic graft versus host disease and its
      oral manifestations. 

PMID- 11507566
TI  - Ewing's sarcoma of the mandible. A case report. 

PMID- 11507567
TI  - Oral rehabilitation with implants in a child with hypohidrotic ectodermal
      dysplasia. 

PMID- 11507569
TI  - Oral lesions in lepromatous leprosy. Presentation of a case and literature
      review. 

PMID- 11507568
TI  - Pseudotumoral hyperplastic form of oral candidiasis. 

PMID- 11507570
TI  - Erytroplakia of the oral cavity. An aggressive premalignant lesion: presentation
      of six case reports. 

PMID- 11507571
TI  - Odontogenic keratocysts. A retrospective study of 285 cases. (I. Clinical
      aspects). 

PMID- 11507572
TI  - Odontogenic keratocysts. A retrospective study of 285 cases. (II.
      Histopathological aspects). 

PMID- 11507573
TI  - Evaluation and prevention of oral complications in patients subjected to bone
      marrow transplantation. A clinical study. 

PMID- 11507574
TI  - Fibrosis of the temporal muscle after injection of a sclerosant: report of a
      case. 

PMID- 11507575
TI  - Recurrent chronic parotiditis in childhood: a report of 61 cases. 

PMID- 11507576
TI  - Odontomas. A clinical-histological and retrospective epidemiological study of 46
      cases. 

PMID- 11507577
TI  - Founding and early history of the American Association for Pediatric
      Ophthalmology and Strabismus.

PMID- 11507578
TI  - Costenbader lecture. Anatomy and surgery of the inferior oblique muscle: recent
      findings.
AB  - BACKGROUND: Surgery of the inferior oblique muscle (IO) has undergone significant
      changes in the past 160 years. Many investigators have contributed to our
      understanding of the action of this muscle and to the surgical options that have
      developed. This article reviews the history of IO surgery with particular
      emphasis on the anterior transposition procedure. METHODS: Anatomic and
      physiologic studies on the neurofibrovascular bundle of the IO are presented.
      RESULTS: The ligamentous structure of the neurofibrovascular bundle of the IO
      provides the ancillary origin for the posterior temporal fibers of the IO when
      its insertion is transposed anteriorly. DISCUSSION: Recent anatomic findings have
      helped explain the effects of the anterior transposition procedure and allow
      further development of our surgical armamentarium for vertical strabismus
      problems. Further nasal transposition of that insertion should reduce or
      eliminate the incidence of the antielevation syndrome. If transposed far nasally,
      the IO could convert to an intorter, as well as to an antielevator and tonic
      depressor.

PMID- 11507579
TI  - Early binocular visual experience may improve binocular sensory outcomes in
      children after surgery for congenital unilateral cataract.
AB  - PURPOSE: To compare the effect of intensive and reduced occlusion therapy
      regimens on binocular sensory outcomes, visual acuity, and the prevalence of
      strabismus in children after surgery for congenital unilateral cataract. METHODS:
      Two nonrandomized groups of patients were studied prospectively: (1) an intensive
      occlusion group (n = 29) patched 80% of waking hours were followed for a median
      6.9 years and (2) a reduced occlusion group (n = 8) patched 25% to 50% of waking
      hours were followed for a median 4.3 years. Six subjects in the intensive group
      and 4 in the reduced occlusion group had secondary intraocular lenses. Two
      subjects in the intensive group had epikeratophakia surgery. Binocular sensory
      function was assessed with random dot and contour stereoacuity tests and the
      Worth 4-dot test. The prevalence and age at onset of strabismus were determined
      from the patients' charts. RESULTS: A higher proportion of subjects in the
      reduced occlusion group (50%) had stereoacuity or fusion compared with the
      intensive occlusion group (14%), a borderline significant difference (P =.08). No
      significant difference (P =.55) was found in median visual acuity between the
      intensive (20/50) and the reduced occlusion (20/55) groups. The 90% prevalence of
      strabismus in the intensive occlusion group was slightly higher than the 63%
      prevalence in the reduced occlusion group, although this difference was not
      significant (P =.18). CONCLUSIONS: These results suggest that a reduced occlusion
      protocol may be associated with better binocular sensory outcomes and a reduced
      prevalence of strabismus without compromising good visual acuity in children
      treated for congenital unilateral cataract.

PMID- 11507580
TI  - Early reoperation after vertical rectus muscle surgery.
AB  - PURPOSE: Adjustable suture strabismus surgery has a success rate between 90% and
      94%. In some patients, undesirable deviations are noted in the first week after
      surgery. In this article, we describe a method of reoperation in the first week
      of the initial repair in an outpatient clinical setting. METHODS: A retrospective
      review of clinical records from 1990 to 1998 identified 7 patients who underwent
      reoperation of the original surgical procedure in a clinic setting. All patients
      had vertical deviations that were overcorrected and had a reversal of their
      diplopia. RESULTS: Follow-up ranged from 3 months to 59 months. All patients were
      free of diplopia and were either orthophoric or had small phoric deviations.
      CONCLUSIONS: Proper identification of patients with strabismus as a result of
      overcorrected adjustable sutures and prompt reoperation in the first week after
      surgery are possible and prevent the need for repeat anesthesia in the operating
      suite.

PMID- 11507581
TI  - Endocyclophotocoagulation for management of difficult pediatric glaucomas.
AB  - INTRODUCTION: Experience with endoscopic diode laser cyclophotocoagulation
      remains limited. We report the efficacy and safety profile of this glaucoma
      surgery technique in the pediatric population. METHODS: Retrospective review of
      51 endoscopic diode laser cyclophotocoagulation procedures performed on 36 eyes
      of 29 pediatric patients with glaucoma over a 6-year period. Surgery was
      performed by using the Microprobe (Endo Optiks, Little Silver, NJ) integrated
      laser endoscope system. Patients were followed-up for a minimum of 6 months or
      until declared treatment failures. Treatment success is defined as a
      postoperative intraocular pressure of < or = 21 mm Hg, with or without adjunctive
      glaucoma medications. RESULTS: Baseline mean pretreatment intraocular pressure
      was 35.06 +/- 8.55 mm Hg. Final postoperative intraocular pressure was 23.63 +/-
      11.07 mm Hg (30% decrease) after an average of 1.42 +/- 0.87 endolaser procedures
      and 19.25 +/- 19.36 months of follow-up. Success rate of the initial procedure at
      last follow-up was 34%. Nine eyes (25%) were retreated at least once. Cumulative
      success rate after all procedures at last follow-up was 43%. Mean cumulative arc
      of treatment was 260 degrees +/- 58 degrees of ciliary processes. Postoperative
      complications included retinal detachment in 2 patients, hypotony in 1 patient,
      and progression of vision loss from hand motion to no light perception in 1
      patient. All 4 complications occurred in aphakic patients. CONCLUSIONS:
      Endoscopic diode laser cyclophotocoagulation is a moderately effective procedure
      for the management of difficult pediatric glaucomas. Aphakic patients may have an
      increased risk of significant postoperative complications, such as retinal
      detachment.

PMID- 11507582
TI  - Orbital wall approach with preoperative orbital imaging for identification and
      retrieval of lost or transected extraocular muscles.
AB  - PURPOSE: To report the results of an anterior approach along the orbital wall to
      recover a lost or transected extraocular muscle. METHODS: This is a retrospective
      review of lost or transected muscles retrieved by an anterior orbitotomy approach
      to the adjacent orbital wall because they were unable to be recovered by a
      standard conjunctival approach. Magnetic resonance imaging or computed tomography
      was performed on all subjects before surgery. RESULTS: Six patients underwent
      anterior orbitotomy via an orbital wall approach; all had undergone an attempted
      retrieval from a standard transconjunctival approach that failed. Five muscles
      had been lost from surgical or traumatic transection, and 1 muscle had been lost
      during strabismus surgery. The muscle location at retrieval ranged from 20 to 25
      mm (mean, 23 mm) posterior to the limbus. The duration that these muscles were
      disinserted ranged from 7 days to 7.5 years (mean, 24 months). Preoperative
      deviation in primary gaze ranged from 15 to 50 PD, whereas first day
      postretrieval deviations all measured less than 8 PD. After a mean follow-up of
      162 weeks, the mean deviation in primary gaze was 2 PD (range, orthotropia to 7
      PD of esotropia). CONCLUSIONS: Anterior orbitotomy along the orbital wall with
      preoperative orbital imaging of extraocular muscle anatomy and function combine
      to create a valuable approach for retrieval of a lost or transected muscle. This
      technique may successfully retrieve lost or transected muscles that previously
      were irretrievable when using a standard transconjunctival approach.

PMID- 11507583
TI  - Pseudophakia and polypseudophakia in the first year of life.
AB  - PURPOSE: To report a consecutive series of patients undergoing intraocular lens
      (IOL) implantation in the first year of life. A new procedure, referred to as
      temporary polypseudophakia, is reported. METHODS: A retrospective chart analysis
      was conducted. Ocular growth and refractive change, complications and reoperation
      rates, and outcomes were analyzed. RESULTS: Forty-seven eyes of 33 patients
      underwent IOL implantation in the first year of life. Average follow-up was 22
      months (range, 7 weeks to 5 years). Thirty-two eyes of 22 patients had a single
      IOL implanted from 12 days to 11 months of age. Fifteen eyes of 11 infants
      received piggyback IOLs from 16 days to 6.8 months of age. Reoperation for
      complications within the anterior segment of the eye was needed in 23% of all
      patients (22% for single IOLs, 26% for piggyback IOLs). The average first
      postoperative refraction after single IOL was +7.98 D and after piggyback IOL was
      +1.67 D. The average last postoperative refraction was +1.76 D and -4.48 D,
      respectively. On average, eyes grew 2.68 mm over 17.5 months of follow-up. Eight
      patients were old enough for Snellen visual acuity, but each had deprivation
      amblyopia with visual acuities from 20/85 to 5/200. Of the remaining 25 patients,
      17 had central, steady, and maintained fixation in the implanted eyes.
      CONCLUSION: IOL implantation in infancy is technically feasible and associated
      with a reoperation rate of approximately 25% in the first 2 years after
      implantation. Further follow-up is required before meaningful visual acuity data
      and long-term results can be reported.

PMID- 11507584
TI  - Follow-up monitoring of accommodative esotropia.
AB  - PURPOSE: To ascertain an examination interval that will not increase the risk of
      untimely detection of decompensation of accommodative esotropia whether or not
      initial nonoperative treatment must be supplemented. METHODS: The records of 63
      patients with accommodative esotropia examined at 3- to 6-month intervals were
      reviewed for the occurrence of decompensation, changes in refraction, and the
      need for increased correction of hyperopia or the addition of bifocals. RESULTS:
      Decompensation, which was not associated with substantial refractive changes
      toward or away from emmetropia, occurred in 11 patients. No instance of
      decompensation occurred in the first 12 months of observation. Although 7 of
      these decompensated patients were among the 18 (28.6%) requiring supplemental
      nonoperative treatment, their mean annual refractive change did not differ
      significantly from the 11 patients who did not decompensate. Eight (18.6%) of 43
      patients first controlled earlier than age 48 months later decompensated; 3
      (15.0%) of 20 patients with later onset reached this outcome. CONCLUSIONS: The
      monitoring of controlled accommodative esotropia at intervals of 9 to 12 months
      is adequate for most patients, at least over the first 2 years, with the
      exception of those requiring treatment for associated conditions such as
      amblyopia. Refractive error changes and the need for supplemental treatment after
      initial control are not prominently associated with decompensation. Age of onset
      of accommodative esotropia earlier or later than 48 months did not influence
      rapidity of decompensation.

PMID- 11507585
TI  - The Amblyopia Treatment Index.
AB  - OBJECTIVE: To develop a questionnaire to assess the acceptability of amblyopia
      treatment and its effect on the child and family. METHODS: A 20-item parental
      survey was developed and pilot tested on 64 subjects, aged 3 to 6 years,
      participating in the Amblyopia Treatment Study, a randomized trial comparing
      patching and atropine as treatments for moderate amblyopia. The survey was
      administered after 4 weeks of treatment. A descriptive item analysis and an
      internal consistency reliability analysis were performed. RESULTS: Nineteen of
      the 20 items demonstrated adequate variability as evidenced by the frequency
      distributions for item responses. Only 4 (<1%) of 1280 possible item responses
      were missing, one each by 4 different respondents. Factor analysis identified 3
      treatment-related factors--"adverse effects," "compliance," and "social stigma"-
      among 11 of the 20 items. The internal-consistency reliability alpha for the 5
      item adverse effects subscale was 0.82, the 4-item compliance subscale alpha was
      0.81, and the 2-item social stigma subscale alpha was 0.84. CONCLUSIONS: The
      Amblyopia Treatment Index appears to be a useful instrument for assessing the
      impact of amblyopia treatment in 3- to 6-year-old children.

PMID- 11507586
TI  - Bilateral ectopia lentis as a presenting feature of medulloepithelioma.
AB  - Ectopia lentis may be a feature of numerous systemic and ocular disorders. Kivela
      and Tarkkanen described an 8-year-old girl with medulloepithelioma who presented
      with ectopia lentis and a mass behind the temporal iris. Shields reported 2
      children with medulloepithelioma who had ectopia lentis associated with
      neovascular glaucoma. To date, there has been no report of a child with ectopia
      lentis as the only presentation of an intraocular tumor. We present 2 children
      with malignant medulloepitheliomas who presented in this fashion.

PMID- 11507587
TI  - Laser photocoagulation in preproliferative retinopathy of incontinentia pigmenti.
AB  - Incontinentia Pigmenti is a rare, X-linked, dominant disorder in which affected
      female infants develop characteristic abnormalities of the skin, central nervous
      system, hair, teeth, and eyes. Ocular abnormalities occur in about 35% of
      patients and consist of proliferative vitreoretinopathy, retinal detachment,
      strabismus, cataract, microphthalmia, optic nerve atrophy, and iris hypoplasia.
      Retinal vascular abnormalities, ranging from peripheral retinal avascularity to
      neovascular and fibrous proliferation with traction retinal detachment, are the
      primary cause of severe visual dysfunction in patients. Therapeutic intervention
      with laser photocoagulation and cryotherapy for the proliferative
      vitreoretinopathy of incontinentia pigmenti has met with variable success. We
      report a case in which laser photocoagulation was used at the onset of
      retinopathy with subsequent resolution of the vasculopathy.

PMID- 11507588
TI  - Bilateral panophthalmitis as the initial presentation of meningococcal meningitis
      in an infant.
AB  - Endophthalmitis is a well-recognized, frequently devastating ophthalmic disease.
      The colonization of the eye and the subsequent development of endophthalmitis may
      be exogenous (including postsurgical and post-traumatic infections) or it may be
      of endogenous origin, representing a metastasis from a focus of infection
      elsewhere in the body associated with bacteremia (such as meningitis or
      cellulitis).

PMID- 11507589
TI  - Patient with Bardet-Biedl syndrome presenting with nystagmus at fifteen months of
      age.
AB  - Bardet-Beidl syndrome (BBS) is an autosomal recessive disorder predominantly
      characterized by dysmorphic distal extremities, obesity, renal abnormalities,
      hypogenitalism, and varying degrees of mental retardation. Other less common
      abnormalities are cardiac and hepatic diseases, anal atresia, cerebellar
      dysfunction, and, in rare cases, nystagmus. This is a report of a child with
      Bardet-Biedl syndrome who presented at 15 months of age with a horizontal and
      rotary nystagmus as the initial sign of this disorder.

PMID- 11507590
TI  - The challenge of pediatric cataract surgery.

PMID- 11507591
TI  - Genetic or environmental causes of esotropia.

PMID- 11507592
TI  - E-optimism on a tide of red ink.

PMID- 11507593
TI  - Bush compromise raises doubts over stem-cell resilience.

PMID- 11507594
TI  - Biologists officially welcome plan.

PMID- 11507595
TI  - Nutritionists question study of organic food.

PMID- 11507596
TI  - Wellcome Trust sets out fresh misconduct standards.

PMID- 11507597
TI  - Academies called to task over human cloning debacle.

PMID- 11507598
TI  - Nigeria takes the initiative in African science.

PMID- 11507599
TI  - Feminized fish encourage Japan to test pollution links.

PMID- 11507600
TI  - Animal data jeopardized by life behind bars.

PMID- 11507601
TI  - Chemistry journal reacts to dispute.

PMID- 11507603
TI  - To boldly go.

PMID- 11507604
TI  - The best supporting actors.

PMID- 11507605
TI  - Organic movement reveals a shift in the social position of science.

PMID- 11507606
TI  - Politics defeats science at environment agency.

PMID- 11507607
TI  - Cooperation among labs is appreciated.

PMID- 11507615
TI  - Stranger than fiction.

PMID- 11507616
TI  - A purgative mastery.

PMID- 11507617
TI  - Quantum ripples in chaos.

PMID- 11507618
TI  - Aerodynamics. Flight of the robofly.

PMID- 11507619
TI  - Quantum physics. Cooperation includes all atoms.

PMID- 11507620
TI  - Neurobiology. Stem cells on the brain.

PMID- 11507621
TI  - Earth science. Gas hydrates and deglaciations.

PMID- 11507623
TI  - Neuroscience. Dynamic categories.

PMID- 11507624
TI  - Planetary science. A new model Moon.

PMID- 11507627
TI  - Finer features for functional microdevices.

PMID- 11507628
TI  - Sex determination. Viviparous lizard selects sex of embryos.
AB  - No one suspected that temperature-dependent sex determination (TSD), whereby the
      sex of embryos depends on the temperature at which they develop, might occur in
      viviparous (live-bearing) reptiles, because thermoregulation in the mother
      results in relatively stable, raised gestation temperatures. But here we show
      that developing embryos of the actively thermoregulating viviparous skink
      Eulamprus tympanum are subject to TSD, offering the mother the chance to select
      the sex of her offspring and a mechanism to help to balance sex ratios in wild
      populations.

PMID- 11507629
TI  - Ancient chronology. Astronomical orientation of the pyramids.
AB  - Spence speculates that Egypt's pyramid builders found true north by using a plumb
      line: when the stars Kochab and Mizar were seen on the same vertical, one was
      facing north. As evidence in support of this hypothesis, she points to the
      proposed interstar-line precession past the north celestial pole at a rate of 27'
      per century (cy). We argue that a mathematical error affects this result, which
      when corrected points more strongly to a different pair of stars. This suggests
      that the conventional ancient chronology, instead of being compressed, may
      actually have to be expanded slightly.

PMID- 11507631
TI  - Structural mimicry in bacterial virulence.
AB  - An important mechanism underlying the strategies used by microbial pathogens to
      manipulate cellular functions is that of functional mimicry of host activities.
      In some cases, mimicry is achieved through virulence factors that are direct
      homologues of host proteins. In others, convergent evolution has produced new
      effectors that, although having no obvious amino-acid sequence similarity to host
      factors, are revealed by structural studies to display mimicry at the molecular
      level.

PMID- 11507632
TI  - Deficiency of molecular hydrogen in the disk of beta Pictoris.
AB  - Molecular hydrogen (H2) is by far the most abundant material from which stars,
      protoplanetary disks and giant planets form, but it is difficult to detect
      directly. Infrared emission lines from H2 have recently been reported towards
      beta Pictoris, a star harbouring a young planetary system. This star is
      surrounded by a dusty 'debris disk' that is continuously replenished either by
      collisions between asteroidal objects or by evaporation of ices on Chiron-like
      objects. A gaseous disk has also been inferred from absorption lines in the
      stellar spectrum. Here we present the far-ultraviolet spectrum of beta Pictoris,
      in which H2 absorption lines are not seen. This allows us to set a very low upper
      limit on the column density of H2: N(H2) </= 1018 cm-2. This non-detection is
      puzzling when compared to the quantity of H2 inferred from the infrared
      observations, but it does show that H2 is not in the disk on the direct line of
      sight. Carbon monoxide (CO) has been seen in absorption against the star,
      yielding a ratio of CO/H2 > 6 x 10-4. As CO would be destroyed under ambient
      conditions in about 200 years (refs 9, 11), our result demonstrates that the CO
      in the disk arises from evaporation of planetesimals.

PMID- 11507633
TI  - Origin of the Moon in a giant impact near the end of the Earth's formation.
AB  - The Moon is generally believed to have formed from debris ejected by a large off
      centre collision with the early Earth. The impact orientation and size are
      constrained by the angular momentum contained in both the Earth's spin and the
      Moon's orbit, a quantity that has been nearly conserved over the past 4.5 billion
      years. Simulations of potential moon-forming impacts now achieve resolutions
      sufficient to study the production of bound debris. However, identifying impacts
      capable of yielding the Earth-Moon system has proved difficult. Previous works
      found that forming the Moon with an appropriate impact angular momentum required
      the impact to occur when the Earth was only about half formed, a more restrictive
      and problematic model than that originally envisaged. Here we report a class of
      impacts that yield an iron-poor Moon, as well as the current masses and angular
      momentum of the Earth-Moon system. This class of impacts involves a smaller-and
      thus more likely-object than previously considered viable, and suggests that the
      Moon formed near the very end of Earth's accumulation.

PMID- 11507634
TI  - Sub-Planck structure in phase space and its relevance for quantum decoherence.
AB  - Heisenberg's principle states that the product of uncertainties of position and
      momentum should be no less than the limit set by Planck's constant, Planck's over
      2pi/2. This is usually taken to imply that phase space structures associated with
      sub-Planck scales (<<Planck's over 2pi) do not exist, or at least that they do
      not matter. Here I show that this common assumption is false: non-local quantum
      superpositions (or 'Schrodinger's cat' states) that are confined to a phase space
      volume characterized by the classical action A, much larger than Planck's over
      2pi, develop spotty structure on the sub-Planck scale, a = Planck's over 2pi2/A.
      Structure saturates on this scale particularly quickly in quantum versions of
      classically chaotic systems-such as gases that are modelled by chaotic scattering
      of molecules-because their exponential sensitivity to perturbations causes them
      to be driven into non-local 'cat' states. Most importantly, these sub-Planck
      scales are physically significant: a determines the sensitivity of a quantum
      system or environment to perturbations. Therefore, this scale controls the
      effectiveness of decoherence and the selection of preferred pointer states by the
      environment. It will also be relevant in setting limits on the sensitivity of
      quantum meters.

PMID- 11507635
TI  - Crystalline ion beams.
AB  - By freezing out the motion between particles in a high-energy storage ring, it
      should be possible to create threads of ions, offering research opportunities
      beyond the realm of standard accelerator physics. The usual heating due to intra
      beam collisions should completely vanish, giving rise to a state of unprecedented
      brilliance. Despite a continuous improvement of beam cooling techniques, such as
      electron cooling and laser cooling, the ultimate goal of beam crystallization has
      not yet been reached in high-energy storage rings. Electron-cooled dilute beams
      of highly charged ions show liquid-like order with unique applications. An
      experiment using laser cooling suggested a reduction of intra-beam heating,
      although the results were ambiguous. Here we demonstrate the crystallization of
      laser-cooled Mg+ beams circulating in the radiofrequency quadrupole storage ring
      PALLAS at a velocity of 2,800 m s-1, which corresponds to a beam energy of 1 eV.
      A sudden collapse of the transverse beam size and the low longitudinal velocity
      spread clearly indicate the phase transition. The continuous ring-shaped
      crystalline beam shows exceptional stability, surviving for more than 3,000
      revolutions without cooling.

PMID- 11507636
TI  - A titanosilicate molecular sieve with adjustable pores for size-selective
      adsorption of molecules.
AB  - Zeolites and related crystalline microporous oxides-tetrahedrally coordinated
      atoms covalently linked into a porous framework-are of interest for applications
      ranging from catalysis to adsorption and ion-exchange. In some of these materials
      (such as zeolite rho) adsorbates, ion-exchange, and dehydration and cation
      relocation can induce strong framework deformations. Similar framework
      flexibility has to date not been seen in mixed octahedral/tetrahedral microporous
      framework materials, a newer and rapidly expanding class of molecular sieves.
      Here we show that the framework of the titanium silicate ETS-4, the first member
      of this class of materials, can be systematically contracted through dehydration
      at elevated temperatures to 'tune' the effective size of the pores giving access
      to the interior of the crystal. We show that this so-called 'molecular gate'
      effect can be used to tailor the adsorption properties of the materials to give
      size-selective adsorbents suitable for commercially important separations of gas
      mixtures of molecules with similar size in the 4.0 to 3.0 A range, such as that
      of N2/CH4, Ar/O2 and N2/O2.

PMID- 11507637
TI  - The timing of the last deglaciation in North Atlantic climate records.
AB  - To determine the mechanisms governing the last deglaciation and the sequence of
      events that lead to deglaciation, it is important to obtain a temporal framework
      that applies to both continental and marine climate records. Radiocarbon dating
      has been widely used to derive calendar dates for marine sediments, but it rests
      on the assumption that the 'apparent age' of surface water (the age of surface
      water relative to the atmosphere) has remained constant over time. Here we
      present new evidence for variation in the apparent age of surface water (or
      reservoir age) in the North Atlantic ocean north of 40 degrees N over the past
      20,000 years. In two cores we found apparent surface-water ages to be larger than
      those of today by 1,230 +/- 600 and 1,940 +/- 750 years at the end of the
      Heinrich 1 surge event (15,000 years BP) and by 820 +/- 430 to 1,010 +/- 340
      years at the end of the Younger Dryas cold episode. During the warm Bolling
      Allerod period, between these two periods of large reservoir ages, apparent
      surface-water ages were comparable to present values. Our results allow us to
      reconcile the chronologies from ice cores and the North Atlantic marine records
      over the entire deglaciation period. Moreover, the data imply that marine carbon
      dates from the North Atlantic north of 40 degrees N will need to be corrected for
      these highly variable effects.

PMID- 11507638
TI  - Direct observation of a submarine volcanic eruption from a sea-floor instrument
      caught in a lava flow.
AB  - Our understanding of submarine volcanic eruptions has improved substantially in
      the past decade owing to the recent ability to remotely detect such events and to
      then respond rapidly with synoptic surveys and sampling at the eruption site. But
      these data are necessarily limited to observations after the event. In contrast,
      the 1998 eruption of Axial volcano on the Juan de Fuca ridge was monitored by in
      situ sea-floor instruments. One of these instruments, which measured bottom
      pressure as a proxy for vertical deformation of the sea floor, was overrun and
      entrapped by the 1998 lava flow. The instrument survived-being insulated from the
      molten lava by the solidified crust-and was later recovered. The data
      serendipitously recorded by this instrument reveal the duration, character and
      effusion rate of a sheet flow eruption on a mid-ocean ridge, and document over
      three metres of lava-flow inflation and subsequent drain-back. After the brief
      two-hour eruption, the instrument also measured gradual subsidence of 1.4 metres
      over the next several days, reflecting deflation of the entire volcano summit as
      magma moved into the adjacent rift zone. These findings are consistent with our
      understanding of submarine lava effusion, as previously inferred from seafloor
      observations, terrestrial analogues, and laboratory simulations.

PMID- 11507639
TI  - Spanwise flow and the attachment of the leading-edge vortex on insect wings.
AB  - The flow structure that is largely responsible for the good performance of insect
      wings has recently been identified as a leading-edge vortex. But because such
      vortices become detached from a wing in two-dimensional flow, an unknown
      mechanism must keep them attached to (three-dimensional) flapping wings. The
      current explanation, analogous to a mechanism operating on delta-wing aircraft,
      is that spanwise flow through a spiral vortex drains energy from the vortex core.
      We have tested this hypothesis by systematically mapping the flow generated by a
      dynamically scaled model insect while simultaneously measuring the resulting
      aerodynamic forces. Here we report that, at the Reynolds numbers matching the
      flows relevant for most insects, flapping wings do not generate a spiral vortex
      akin to that produced by delta-wing aircraft. We also find that limiting spanwise
      flow with fences and edge baffles does not cause detachment of the leading-edge
      vortex. The data support an alternative hypothesis-that downward flow induced by
      tip vortices limits the growth of the leading-edge vortex.

PMID- 11507640
TI  - Change in pattern of ongoing cortical activity with auditory category learning.
AB  - Humans are able to classify novel items correctly by category; some other animals
      have also been shown to do this. During category learning, humans group
      perceptual stimuli by abstracting qualities from similarity relationships of
      their physical properties. Forming categories is fundamental to cognition and can
      be independent of a 'memory store' of information about the items or a prototype.
      The neurophysiological mechanisms underlying the formation of categories are
      unknown. Using an animal model of category learning, in which frequency-modulated
      tones are distinguished into the categories of 'rising' and 'falling' modulation,
      we demonstrate here that the sorting of stimuli into these categories emerges as
      a sudden change in an animal's learning strategy. Electro-corticographical
      recording from the auditory cortex shows that the transition is accompanied by a
      change in the dynamics of cortical stimulus representation. We suggest that this
      dynamic change represents a mechanism underlying the recognition of the abstract
      quality (or qualities) that defines the categories.

PMID- 11507641
TI  - Purification of a pluripotent neural stem cell from the adult mouse brain.
AB  - The adult mammalian central nervous system (CNS) contains a population of neural
      stem cells (NSCs) with properties said to include the generation of non-neural
      progeny. However, the precise identity, location and potential of the NSC in situ
      remain unclear. We purified NSCs from the adult mouse brain by flow cytometry,
      and directly examined the cells' properties. Here we show that one type of NSC,
      which expresses the protein nestin but only low levels of PNA-binding and HSA
      proteins, is found in both ependymal and subventricular zones and accounts for
      about 63% of the total NSC activity. Furthermore, the selective depletion of the
      population of this stem cell in querkopf mutant mice (which are deficient in
      production of olfactory neurons) suggests that it acts as a major functional stem
      cell in vivo. Most freshly isolated NSCs, when co-cultured with a muscle cell
      line, rapidly differentiated in vitro into myocytes that contain myosin heavy
      chain (MyHC). This demonstrates that a predominant, functional type of stem cell
      exists in the periventricular region of the adult brain with the intrinsic
      ability to generate neural and non-neural cells.

PMID- 11507642
TI  - Antibodies inhibit prion propagation and clear cell cultures of prion
      infectivity.
AB  - Prions are the transmissible pathogenic agents responsible for diseases such as
      scrapie and bovine spongiform encephalopathy. In the favoured model of prion
      replication, direct interaction between the pathogenic prion protein (PrPSc)
      template and endogenous cellular prion protein (PrPC) is proposed to drive the
      formation of nascent infectious prions. Reagents specifically binding either
      prion-protein conformer may interrupt prion production by inhibiting this
      interaction. We examined the ability of several recombinant antibody antigen
      binding fragments (Fabs) to inhibit prion propagation in cultured mouse
      neuroblastoma cells (ScN2a) infected with PrPSc. Here we show that antibodies
      binding cell-surface PrPC inhibit PrPSc formation in a dose-dependent manner. In
      cells treated with the most potent antibody, Fab D18, prion replication is
      abolished and pre-existing PrPSc is rapidly cleared, suggesting that this
      antibody may cure established infection. The potent activity of Fab D18 is
      associated with its ability to better recognize the total population of PrPC
      molecules on the cell surface, and with the location of its epitope on PrPC. Our
      observations support the use of antibodies in the prevention and treatment of
      prion diseases and identify a region of PrPC for drug targeting.

PMID- 11507643
TI  - Iron deficiency induces the formation of an antenna ring around trimeric
      photosystem I in cyanobacteria.
AB  - Although iron is the fourth most abundant element in the Earth's crust, its
      concentration in the aquatic ecosystems-particularly the open oceans-is
      sufficiently low to limit photosynthetic activity and phytoplankton growth.
      Cyanobacteria, a major class of phytoplankton, respond to iron deficiency by
      expressing the 'iron-stress-induced' gene, isiA(ref. 3). The protein encoded by
      this gene has an amino-acid sequence that shows significant homology with one of
      the chlorophyll a-binding proteins (CP43) of photosystem II (PSII). The precise
      function of the CP43-like protein, here called CP43', has not been elucidated,
      although there have been many suggestions. Here we show that CP43' associates
      with photosystem I (PSI) to form a complex that consists of a ring of 18 CP43'
      molecules around a PSI trimer. This significantly increases the size of the light
      harvesting system of PSI. The utilization of a PSII-like protein as an extra
      antenna for PSI emphasises the flexibility of cyanobacterial light-harvesting
      systems, and seems to be a strategy which compensates for the lowering of
      phycobilisome and PSI levels in response to iron deficiency.

PMID- 11507644
TI  - A giant chlorophyll-protein complex induced by iron deficiency in cyanobacteria.
AB  - Cyanobacteria are abundant throughout most of the world's water bodies and
      contribute significantly to global primary productivity through oxygenic
      photosynthesis. This reaction is catalysed by two membrane-bound protein
      complexes, photosystem I (PSI) and photosystem II (PSII), which both contain
      chlorophyll-binding subunits functioning as an internal antenna. In addition,
      phycobilisomes act as peripheral antenna systems, but no additional light
      harvesting systems have been found under normal growth conditions. Iron
      deficiency, which is often the limiting factor for cyanobacterial growth in
      aquatic ecosystems, leads to the induction of additional proteins such as IsiA
      (ref. 3). Although IsiA has been implicated in chlorophyll storage, energy
      absorption and protection against excessive light, its precise molecular function
      and association to other proteins is unknown. Here we report the purification of
      a specific PSI-IsiA supercomplex, which is abundant under conditions of iron
      limitation. Electron microscopy shows that this supercomplex consists of trimeric
      PSI surrounded by a closed ring of 18 IsiA proteins binding around 180
      chlorophyll molecules. We provide a structural characterization of an additional
      chlorophyll-containing, membrane-integral antenna in a cyanobacterial
      photosystem.

PMID- 11507648
TI  - Nodular goiter and goiter nodules: Where iodine deficiency falls short of
      explaining the facts.
AB  - While the concept of iodine deficiency (ID) still dominates most discussions
      about the pathogenesis of multinodular goiter (MNG), the present review focuses
      on those mechanisms that may cause MNG in the absence of ID. Among the many
      facets of MNG that cannot simply be explained by ID, are the frequent occurrence
      of the disease in patients not exposed to ID, the autonomous growth of goiters -
      often accompanied by subclinical or even overt thyrotoxicosis -, the inverse
      relationship between goiter size and serum TSH, the multifocal, heterogeneous and
      nodular growth pattern, the heterogeneity of function with the familiar patchy
      iodine metabolism on scintiscans, the growth of clonal and polyclonal nodules,
      the prominent genetic predisposition. Even the notoriously low intrathyroidal
      iodine concentration - common to endemic as well as to sporadic goiter - is a
      secondary, rather than a primary event. Thus, the fundamental process of
      goitrogenesis, is independent from ID but operates through mechanisms innate to
      the hereditary and acquired heterogeneity among the thyrocytes themselves. In
      this view, goiter nodules and nodular goiters are true benign neoplasias arising
      by mechanisms common to all benign endocrine and nonendocrine neoplasms. However,
      superimposed iodine shortage greatly enhances the incidence of MNG and shifts its
      clinical appearance toward younger ages by adding one more growth factor -
      presumably enhanced TSH secretion - to an intrinsically activated growth
      regulating network.

PMID- 11507649
TI  - Expression of arginine vasopressin and vasopressin V1a receptor mRNA in diabetic
      (db/db) mice.
AB  - To assess the involvement of arginine vasopressin (AVP) in genetical diabetic
      (db/db) mice, we examined the mRNA expression levels of AVP and vasopressin V(1a)
      receptors (V(1a)R) in brain and liver of db/db mice. In 10 week-old db/db mice, a
      significant elevation in blood sugar levels and plasma osmolality were observed,
      showing obvious diabetic symptoms. There was a significant increase in brain AVP
      mRNA levels in db/db mice. The expression level of liver V(1a)R mRNA in db/db
      mice was significantly down-regulated, presumably as a consequence of ligand
      receptor interaction. This is in contrast to results that show no significant
      reduction in brain V(1a)R mRNA levels when comparing db/db and control mice.
      Thus, it is possible that in the progress of genetic diabetes mellitus, AVP acts
      in liver than in brain through V(1a)R.

PMID- 11507650
TI  - Systemic insulin-like growth factor-I, insulin and vitamin D status in relation
      to age-associated bone loss in women.
AB  - This cross-sectional study, performed on 146 healthy (n = 64) or osteoporotic but
      otherwise normal (n = 82) pre- (n = 38) or post-menopausal (n = 108) female
      subjects, analyzed the relationships between bone mineral density (BMD) (measured
      by dual-energy X-ray absorptiometry), parameters of bone remodelling, indices of
      calcium homeostasis and systemic IGF-I or insulin levels against a background of
      natural aging. BMD (g/cm(2)) at the hip correlated to serum IGF-I concentration
      (r = 0.207, p < 0.05), as well as to insulin levels (r = 0.241, p < 0.01), while
      BMD at the spine correlated only to IGF-I levels (r = 0.173, p < 0.05). After
      adjustment for age, body mass index, serum PTH, vitamin D status and calcitonin
      levels, neither IGF-I nor insulin levels could be significantly related to BMD at
      the spine or hip. On the other hand, 25-OH vitamin D(3) was found to be an
      important predictor of BMD at the hip (beta = 0.1686, p = 0.0437). In conclusion,
      this study failed to demonstrate a predictive importance of insulin-IGF-I axis to
      the development of bone mass. Instead, a significant predictive value to BMD at
      the hip was documented for serum 25-OH vitamin D(3).

PMID- 11507651
TI  - Progressive histopathological changes in pancreatic islets of Zucker Diabetic
      Fatty rats.
AB  - Thus far, histopathological changes in the pancreatic islets of Zucker Diabetic
      Fatty (ZDF) rats, an animal model of type 2 diabetes mellitus (or non-insulin
      dependent diabetes mellitus), have only been studied in male rats and in 18-weeks
      old rats or younger. In this study, we have examined in both male and female ZDF
      rats the histopathological changes longitudinally, from 6 to 32 weeks of age. We
      studied islet architecture and cellular distribution of the various islet
      hormones both in ZDF and control rats. In the ZDF rats, aging was initially
      associated with an enlargement of the islets. From 18 weeks onwards, no further
      enlargement was noted but islet boundaries became increasingly irregular, leading
      to the appearance of projections of endocrine cells into the surrounding exocrine
      tissue. At the islet boundaries as well as within the islets progressive fibrosis
      was observed with increasing amounts of collagen and reticular fibers. In the
      islets, staining intensity of both insulin and islet amyloid polypeptide (IAPP)
      increased slightly till 10 weeks of age and thereafter decreased rapidly. In
      contrast, the staining intensities of glucagon, somatostatin, and pancreatic
      polypeptide (PP) did not change. Even at the age of 32 weeks, just the beta-cells
      and not the other endocrine islet cells appear to be affected. In control rats,
      aging evoked only minor changes. Thus, we observed that during prolonged
      development of diabetes mellitus in both male and female ZDF rats
      histopathological changes in the pancreatic islets became progressively more
      severe, eventually leading to disintegration of the islets.

PMID- 11507652
TI  - Search for mitochondrial DNA mutation at position 3243 in German patients with a
      positive family history of maternal diabetes mellitus.
AB  - Mitochondrial diabetes is one of the most common monogenetic forms of diabetes
      mellitus. However, variable prevalences have been reported by different
      investigators. Therefore, the aim of our study was to investigate the prevalence
      of the most prevalent mitochondrial DNA mutation at position 3243 (A --> G) in
      german patients with a positive family history of maternally inherited diabetes
      mellitus and/or hearing loss. We screened 1460 patients with diabetes mellitus by
      a questionnaire and identified 122 patients with a positive family history of
      maternal diabetes mellitus. Seven of the 122 patients suffered from hearing loss
      in addition. An EDTA blood sample of each patient was examined by polymerase
      chain reaction followed by a digestion with Bsp120I. In addition all samples were
      further examined by denaturing gradient gel electrophoresis to increase the
      detection limit for heteroplasmy. Only one mt DNA mutation at position 3243 could
      be detected in the 122 patients. The detection limit of denaturing gradient gel
      electrophoresis (DGGE) for heteroplasmy was 3%. We detected one new polymorphism
      at position 3333 (C --> T) of the mitochondrial genome (0.8% of the patients),
      and a known polymorphism at position 3197 (T --> C) in 10.6% of the patients. We
      therefore conclude that the frequency of the A3243G mutation is much lower in the
      investigated study population, mostly originating from Saxonia, than in asian
      populations.

PMID- 11507653
TI  - Are levels of bone turnover related to lower bone mass of adolescents previously
      fed a macrobiotic diet?
AB  - Dutch adolescents who consumed a macrobiotic (vegan-type) diet in early life,
      demonstrate a lower relative bone mass than their omnivorous counterparts. We
      investigated whether subjects from the macrobiotic group showed signs of catching
      up with controls in terms of relative bone mass, reflected by higher levels of
      serum osteocalcin and alkaline phosphatase and lower levels of urinary cross
      links. Group differences in calciotropic hormones and mineral excretion were also
      investigated. Bone measurements, blood, and urine samples were obtained from 69
      macrobiotic (34 girls, 35 boys) and 99 control (57 girls, 42 boys) subjects, aged
      9-15. Bone turnover markers and 1,25(OH)2D reached maximal levels at pubertal
      stages 3-4, and decreased thereafter. After adjusting for puberty, age, and lean
      body mass, no group differences were found in markers of bone turnover,
      1,25(OH)2D, PTH, or calcium excretion, but phosphate excretion was 23% lower in
      macrobiotic girls. After adjustment for puberty, 1,25(OH)2D was positively
      related to osteocalcin. In summary, we found no evidence for group differences in
      bone turnover, or catch up in relative bone mass, which might be due to the fact
      that 60% of subjects were still in early stages of puberty.

PMID- 11507654
TI  - Investigations on the activity of bovine placental oestrogen sulfotransferase and
      -sulfatase from midgestation to parturition.
AB  - To gain further information on the biological role of the high amounts of
      conjugated estrone (E1S) secreted by the bovine placenta, an in vitro assay
      system was developed to measure oestrogen sulfotransferase (OST) and oestrogen
      sulfatase (OS) activities in caruncular and cotyledonary homogenates and the
      respective subcellular fractions. Placental tissue was obtained from 150 (n = 3),
      220 (n = 4), 240 (n = 3) and 270 days (n = 3) pregnant and parturient cows (n =
      4). 3H-E1 and 3H-E1S served as substrates and 4-nitrophenyl sulfate potassium
      salt was used as a competitive inhibitor to block OS when testing for OST
      activity. OST-activity did not change during pregnancy and parturition and was
      higher (p < 0.001) in cotyledonary than in caruncular tissue with mean
      conversions (median) of 61.8% and 41.6% after 30 min of homogenate incubation. On
      a subcellular level OST-activity was clearly associated with the cytosol. OS
      activity was higher (p < 0.001) in caruncular than in cotyledonary homogenates;
      it was constant during pregnancy (median of conversion: 88.0% and 66.4%, resp.),
      but was significantly decreased (p < 0.05) at parturition (median of conversion:
      48.1% and 30.6%, resp.). On a subcellular level in both the cotyledon and the
      caruncle highest OS-activities were detected in the microsomal and the
      mitochondrial fractions. The decreased placentomal OS-activities in parturient
      cows are inconsistent with a substantial role of OS in the prepartal increase of
      free oestrogens. These results also suggest that bovine placental oestrogens may
      largely exert their action locally within the placentomes during most time of
      gestation as the enzymes catalyzing sulfoconjugation (i.e. inactivation of free
      oestrogens) and desulfation (i.e. activation of conjugated oestrogens) are
      expressed in close proximity to each other. In this respect the finding of
      oestrogen receptors in caruncular stromal cells is of particular interest.

PMID- 11507655
TI  - Changes in cerebral glucose metabolism and visuospatial capability in hypogonadal
      males under testosterone substitution therapy.
AB  - Genders differ concerning abilities of spatial cognition; positive associations
      of testosterone levels with corresponding scores have been reported, as well. We
      addressed the question whether there is a testosterone-susceptible area within
      cerebral structures previously described to be involved in mental rotation. Using
      F-18-deoxyglucose (FDG)-positron emission tomography (PET), we studied cerebral
      glucose metabolism during a standardized 3-dimensional mental rotation task in 6
      right-handed men with hypogonadotropic hypogonadism before and under testosterone
      substitution therapy. Under elevated testosterone levels, enhanced cerebral
      glucose metabolism during mental rotation was observed in the 4 subjects with
      improved visuospatial capability. Areas involved were previously demonstrated to
      be activated by such tasks in eugonadal men.

PMID- 11507657
TI  - [The importance of the Heidelberg Medical School in the development of medicine
      in the 20th century].

PMID- 11507658
TI  - [Nikolaus Friedreich, the first Heidelberg "neurologist"].

PMID- 11507659
TI  - [Wilhelm Erb, founder and first president of the German Society of Neural
      Medicine].

PMID- 11507660
TI  - [Johann Hoffmann, first professor of neuropathology in Heidelberg].

PMID- 11507661
TI  - [The neurologic roots of psychosomatic medicine].

PMID- 11507662
TI  - [Viktor von Weizsacker, a founder of psychosomatic medicine].

PMID- 11507663
TI  - [The relationship of psychiatry to neurology in the twenties and thirties of the
      past century in Heidelberg].

PMID- 11507664
TI  - [Prof. Dr. Paul Vogel--representative of clinical neurology].

PMID- 11507665
TI  - [Heinz Ganshirt --forerunner of research on cerebrovascular diseases in Germany].

PMID- 11507666
TI  - [Neurology in Heidelberg today--impressions of an interested observer].

PMID- 11507667
TI  - [Caries prevalence and state of treatment in the case of Koblenz children in the
      first school class with reference to district-related social indicators].
AB  - The findings of the dental medical examinations of the school years 1996/1997 and
      1997/1998 in the first classes of primary schools in Koblenz have been associated
      with district-related social indicators given in the social report for Koblenz,
      and more especially the "proportion of recipients of social welfare assistance
      among the 0-13 year-olds" indicator. The caries prevalence indices as well as the
      treatment deficits, the proportion of those needing treatment and the proportion
      of children with increased risk of caries clearly increased parallel with the
      proportion of social welfare assistance amongst the children although the
      greatest difference was seen in the case of districts with average social welfare
      assistance density and such with high/very high social welfare assistance
      density. Even at individual school levels a close connection could be established
      between the proportion of social welfare assistance recipients amongst the 0-13
      year-olds in the school district and a) the proportion of children with increased
      caries risk in accordance with DAJ (Deutsche Arbeitsgemeinschaft fur
      Jugendzahnpflege) criteria (r(s) = + 0.881) as well as b) a multi-factorial
      "first school class dental health index" (EZI) (which covered both prevalence and
      treatment parameters and also findings below the risk threshold of the DAJ
      criteria) developed for comparing the schools with each other (r(s) = + 0.825).
      The six "risk schools" (from 22 primary schools) determined by a) the proportion
      of children with increased caries risk according to DAJ criteria, b) the multi
      factorial EZI and c) the social welfare assistance proportion amongst the 0-13
      year-olds in the school district, are identical. In comparison with the complex
      multi-factorial first school class dental health index (EZI), the study confirms
      the general suitability of the "proportion of children with increased caries
      risk" for the identification of schools with above-average deficit in dental
      health care. However, at the same time such "risk schools" - at least in the
      towns with documented social differentiation of the resident population in the
      various town districts - can also be determined by the district-related social
      indicators. This may be significant in such cases where there are no dental
      examination results (determined according to uniform criteria) available for all
      schools in one town or region, but specific measures (for example examinations,
      prevention, fluoridation) should be concentrated on schools with greater need for
      such measures.

PMID- 11507668
TI  - [Prevention of congenital malformations by means of folic acid - insurmountable
      problems due to the German penal code and German drug legislation when preparing
      a preconceptional model in Saxony-Anhalt].
AB  - For the last 20 years the prophylactic effect of the vitamin folic acid against
      the occurrence of neural tube defects has been known but in Germany this fact has
      not been realized by the public. The recommendations by medical institutions
      fail, among other reasons, because a folic acid prescription by gynaecologists
      comes too late in the course of events, i.e., women go to the gynaecologist when
      pregnancy has already set in and it is too late for preventive measures. An
      effective folic acid prophylaxis must take place before the onset of pregnancy.
      Data from the regional surveillance of congenital anomalies of the German Federal
      State of Saxony-Anhalt and interviews with women in maternity, as well as
      gynaecologists, indicate that there is a substantial knowledge deficit concerning
      folic acid prophylaxis. In 1998, therefore, a working group was set up in Saxony
      Anhalt. It comprises representatives from interested institutions and has the
      goal of rectifying the knowledge deficit of women of childbearing age by way of a
      broad-based campaign while making use of the results of regional congenital
      anomalies monitoring. A pharmaceutical company was enlisted for cost-free
      distribution of its folic acid product. Legal problems with the prescription drug
      laws, the law against unfair competitive practices, the advertising of
      medicaments law and the SGB V (social code) made it impossible to procure
      multivitamins containing folic acid free of charge for women wanting a child. A
      highly differentiated legislation has hitherto prevented an elementary
      improvement in prevention.

PMID- 11507669
TI  - [Comparative hospital tours: visiting the oasis of psychiatry].
AB  - AIM: Currently, financial sponsors and Government officials of the relevant
      ministries responsible for the German health care system request comparative
      length-of-stay figures in hospitals as indicators of efficacy of inpatient
      treatment. In psychiatry such comparisons are considered doubtful because of the
      heterogeneity of patients in different hospitals. This study compares the length
      of stay in eight German psychiatric hospitals accounting for individual as well
      as organisational characteristics. METHODS:  SAMPLE: 27,792 patient records
      according to the DGPPN-BADO (the standardized psychiatric assessment and
      discharge battery in Germany) from eight hospitals with a total of 135 wards.
      STATISTICAL ANALYSIS: Variance components modelling with random effects using
      three levels (patients, wards, hospitals). RESULTS: After adjustment for patient
      and organisational characteristics, there were no significant differences in the
      average length of stay between the eight hospitals. CONCLUSIONS: Hospital
      comparisons of quality of care require a multilevel approach. Based on our
      results further comparisons and implementation of quality improvements in
      inpatient psychiatry should focus on the ward level.

PMID- 11507670
TI  - [The social security system as a topic in medical education. Own experiences and
      description of student's contribution].
AB  - INTRODUCTION: The special subject "sociomedicine", as defined for medical
      students in "items to which the written examination in the second part of the
      medical examination can relate" has been taught by this department for 25 years
      as part of the course on medical ecology. There are 4 lectures (structure of the
      health care system; preventive care by doctors in the community and at the place
      of work; introduction to health economy; introduction to epidemiology) and the
      following seminars in small groups: social security systems; health insurance;
      excursion to a rehabilitation hospital; health reporting; epidemiology. The
      topics are presented and taught with emphasis on didactically useful and local
      examples. METHODS: To ensure student participation "personal data" were
      introduced: Students give short reports on topics presented to them or they have
      to formulate questions to the topic of the seminar, questions or subjects to be
      dealt with. The questions concerning "social security systems" and "health
      insurance", collected over a 6 year period, were analyzed. RESULTS: Initially,
      the subject "sociomedicine" is not much appreciated by the students. The analysis
      shows what students think when they are challenged. The spectrum of questions
      mainly reflects the discussion in the media: Finance and benefits predominate,
      also budget and misuse, especially with reference to old-age pension and health
      insurance. Questions related to specific medical functions as e. g. medical
      expert opinion, are less often raised. However, topics such as "expansion of
      preventive measures", "chip card and utilisation" and "unconventional methods"
      are often addressed. A special demand for personal advice is seen during small
      talk discussions in intermissions (health insurance). CONCLUSION: The topics
      "medical expert opinion" and "comparison of public and private health insurance"
      have become positive knowledge required for the examination and for practising
      the medical profession. With these subjects as a starting point it appears easier
      for us to describe the relevant institutions and structures and the general
      principles of solidarity.

PMID- 11507671
TI  - [Methicillin-resistant Staphylococcus aureus in long-term care facilities for the
      aged in Frankfurt am Main, Germany, in 1999].
AB  - In recent years problems with multiple resistant bacteria, including methicillin
      resistant Staphylococcus aureus (MRSA) in hospitals have been increasing world
      wide. Moreover, nursing home residents have also been found to be colonised with
      MRSA. In 1999, the Robert Koch Institute, Berlin inaugurated a multicenter study
      on the prevalence of MRSA colonisation in residents of old-age nursing homes in
      Germany. Here, the data from the city of Frankfurt will be reported. COLLECTIVES
      AND METHODS: With the informed consent of 359 residents from 7 old-age
      pensioners' homes and 42 patients of a geriatric rehabilitation unit, nasal and
      pharyngeal swaps were taken and tested for MRSA. Age, sex, duration of the stay
      in the home, former hospital admissions, acute and chronic diseases and medical
      devices such as urinary catheters were asked using a questionnaire. In addition
      including 150 employees (mainly nurses) of these institutions were tested for
      MRSA as well. RESULTS: None of the employees tested were MRSA-positive. MRSA was
      found in 10 out of 401 residents/patients (2.4 %), i. e. 4.8 % of the patients
      and 2.2 % of the residents. As risk factors for colonisation of the residents
      could be found: male sex (Odds ratio 4.7, 95 % confidence interval 95CI 1.3
      16.9), stay in the institution for less than 1 year (OR = 17.4; 95CI: 2.2-141)
      and former MRSA-colonisation (OR = 24.2; 95CI: 3.9-152). In addition, we got
      hints that former hospital admission was a risk factor for colonisation with MRSA
      (OR = 3; 95CI: 0.6-14.4). Residents with ulcus, decubiti and peripheral
      circulatory disorder were at double risk for MRSA colonisation (not significant).
      DISCUSSION AND CONCLUSIONS: The prevalence of MRSA colonisation in the residents
      of the old-age pensioners homes in Frankfurt am Main, Germany, was 2.4 %, which
      is (still?) low. There were no hints available for the spread of MRSA within the
      homes, although in 7 of 8 MRSA-positive residents MRSA colonisation was not known
      previously, so that no special hygienic regime was applied. Therefore, US
      American and British guidelines for the control of MRSA in nursing homes were
      confirmed: a good hygienic regime, especially correct hand hygiene is the most
      important measure to prevent the spread of MRSA within the nursing homes. In
      general, isolation of the colonised residents is not necessary, unless in very
      special individual cases.

PMID- 11507672
TI  - [Existing and possible working areas for social workers in the public health
      service of Berlin and Brandenburg].
AB  - Standardised questionnaires were used to examine in which Public Health Service
      areas of Berlin and Brandenburg (Germany) social workers are currently active.
      The main goal was to ascertain the working approaches and primary areas of their
      activities. Another aim was to look into the co-operation between public health
      service and resident doctors, mutual aid groups, out-patient services and social
      services in other institutions (hospitals, health insurance, services for
      disabled persons and nursing homes). It was also examined whether current social
      and economical changes raise a need for new counselling offers from the public
      health service for other target groups (unemployed, women and homeless persons).

PMID- 11507673
TI  - Progesterone differentially regulates the membrane-type matrix metalloproteinase
      1 (MT1 -MMP) compartment of proMMP-2 activation in MG-63 cells.
AB  - Osteoblast-derived matrix metalloproteinases (MMPs) are considered to play a
      crucial role in bone formation and initiation of bone resorption by degrading the
      bone matrix. MMP-2 is constitutively secreted in a latent zymogen by osteoblasts,
      and requires the process of activation mediated by membrane-type matrix
      metalloproteinase-1 (MT1-MMP)/tissue inhibitor of metalloproteinase (TIMP-2)
      complex in the cell surface. Bone is one target tissue for progestins. In the
      present study, we observed the effects of progesterone on proMMP-2 activation and
      MT1-MMP expression, and also TIMP-2 levels in osteoblastic MG-63 cells. Gelatin
      zymograms and ELISA showed that progesterone have no effects on proMMP-2
      activation. Using Western immunoblot analysis, we unexpectedly found that
      treatment with increasing doses of progesterone in MG-63 cells caused a dose
      dependent increase in expression of MT1-MMP protein, and after 48h treatment,
      progesterone at 10(-8)M increased MT1-MMP protein level. Confocal
      immunohistochemistry analysis also confirmed that progesterone induced MT1-MMP
      expression in MG-63 cells. The results of Northern blot analysis showed that
      progesterone at 10(-8)M increased MT1-MMP protein levels after 48 h treatment. We
      also found that TIMP-2 levels were undetectable in MG-63 cells. In conclusion,
      progesterone increases MT1-MMP protein and mRNA levels in MG-63 cells, but has no
      effects on proMMP-2 activation, which is partly attributable to the undetectable
      levels of tissue inhibitor of metalloproteinase-2 (TIMP-2). Our studies suggest
      that TIMP-2 is involved in proMMP-2 activation, and regulation of MT1-MMP by
      progesterone may contribute to its actions on bone formation.

PMID- 11507675
TI  - Expression and distribution of the prolactin receptor in normal rat liver and in
      experimental liver cirrhosis.
AB  - Recent results have suggested a role for prolactin (PRL) as a regeneration factor
      in the liver. In order to investigate the involvement of prolactin in the
      pathogenesis of liver cirrhosis, we studied the expression of the prolactin
      receptor (PRLR) and PRL during the development of cirrhosis in an animal model.
      30 male rats were exposed to CCl4 by inhalation. Phenobarbitone was added to the
      drinking water to accelerate the formation of toxic metabolites by enzyme
      induction. Two control groups of 30 animals each were treated with phenobarbitone
      only or received no treatment. 10 animals of each group were sacrificed 35, 55,
      and 70 days after initiation of treatment. Liver tissue was subjected to
      histological examination, which demonstrated fibrosis of different grades and
      cirrhosis in the CCl4-treated rats. Expression of PRLR mRNA was investigated by
      mRNA extraction, RT-PCR and computer-supported densitometric evaluation. Compared
      to control liver, PRLR mRNA was expressed at a higher level in fibrotic and
      cirrhotic liver specimens. In normal tissue, immunohistochemical staining showed
      a high concentration of PRLR around the central vein and in the epithelium of the
      bile ducts. This pattern of distribution was lost in fibrosis and cirrhosis. An
      accumulation of PRLR was demonstrated within the damaged cells. Neither PRL nor
      PRL mRNA was detectable in normal, fibrotic, or cirrhotic liver. We conclude that
      PRLR is distributed in normal rat liver in a typical pattern which is lost with
      increasing fibrosis. PRL is not produced by rat liver, indicating that PRL does
      not act through autocrine or paracrine mechanisms.

PMID- 11507674
TI  - Expression of HDL receptor, CLA-1 in human smooth-muscle cells and effect of
      interferon-gamma on its regulation.
AB  - High-density lipoprotein (HDL) exerts antiatherogenic effects by various
      mechanisms. The protective effect of HDL is thought to involve the reverse
      transport of cholesterol from cells in the arterial wall to the liver for
      disposal. We previously identified human scavenger receptor BI (hSR-BI/CLA-1) as
      a receptor for human HDL, but did not examine the expression of hSR-BI/CLA-1 in
      smooth-muscle cells. In this present study, a human aortic intima smooth-muscle
      cell line immortalized with SV 40 DNA was established, and the expression of hSR
      BI/CLA-1 in this cell line analyzed by Western blot and RT-PCR. HSR-BI/CLA-1 mRNA
      and protein were detected in both this cell line and primary human aortic smooth
      muscle cells. A cytokine, interferon-gamma (IFN-gamma) inhibited the hSR-BI/CLA-1
      protein expression, but not mRNA expression. This observation confirmed that
      selective cholesterol ester uptake from HDL was inhibited by IFN-gamma. These
      results indicated that hSR-BI/CLA-1 may be expressed in human smooth-muscle
      cells, and the expression may be modulated by IFN-gamma. HSR-BI/CLA-1 on smooth
      muscle cells could play an important role in atherogenesis.

PMID- 11507676
TI  - Potential role of Gab1 and phospholipase C-gamma in osmotic shock-induced glucose
      uptake in 3T3-L1 adipocytes.
AB  - Osmotic shock induces GLUT4 translocation and glucose uptake through a mechanism
      independent of PI 3-kinase, but dependent on tyrosine phosphorylation of cellular
      proteins. To identify the tyrosine phosphorylated proteins required for osmotic
      shock-stimulated glucose uptake, we examined tyrosine phosphorylation of
      candidate proteins, and found that the 60-80kDa species including paxillin and
      the 120-130kDa species including p130Cas, PYK2, FAK and Gab1 were tyrosine
      phosphorylated in response to osmotic shock. Inhibition of actin polymerization
      by cytochalasin D significantly decreased the tyrosine phosphorylation of
      paxillin, p130Cas, PYK2 and FAK but not Gab1, but had no effect on 2-deoxyglucose
      (DOG) uptake, suggesting a role for Gab1 in osmotic shock-induced glucose
      transport. Also, we found that osmotic shock increases the association of
      phospholipase C-gamma (PLC-gamma) with Gab1 and stimulates tyrosine
      phosphorylation of PLC-gamma itself. The PLC inhibitor, U73122, inhibited osmotic
      shock-induced 2-DOG uptake. These results suggest that tyrosine phosphorylation
      of Gab1 and subsequent recruitment and activation of PLC-gamma may play a role in
      osmotic shock-induced glucose transport.

PMID- 11507677
TI  - Modulation of corticosterone availability to white adipose tissue of lean and
      obese Zucker rats by corticosteroid-binding globulin.
AB  - Corticosterone-binding (CB) capacity was determined in periovarian and
      subcutaneous white adipose tissue (WAT), as well as in plasma of lean and obese
      Zucker rats. In lean rats, plasma CB was twice the level of obese rats. In lean
      rat WAT, dexamethasone binding accounted for only 0.05-0.09% of corticosterone
      binding, and aldosterone bound even less; in the obese rats, dexamethasone
      accounted for 0.2 - 0.3 % of corticosterone binding. Scatchard plots showed that
      KD for corticosterone was 3.1 nM (WAT) or 3.4 nM (plasma) in lean rats and 1.8 nM
      (WAT) or 1.5 nM (plasma) in obese rats. The total CB capacity in WAT was lower in
      the obese than in lean rats (47-50%). Plasma non-esterified fatty acid levels
      were higher in obese rats. The results suggest that CBG may limit the access of
      glucocorticoids to adipocytes more weakly in obese rats because of the lower CBG.
      Fatty acids may increase the affinity of CBG for corticosterone, which would make
      WAT cells less accessible to circulating glucocorticoids. The modulation of CBG
      by fatty acids may protect fat reserves by decreasing the sensitivity of WAT to
      glucocorticoids.

PMID- 11507678
TI  - Pre-heparin plasma lipoprotein lipase mass: correlation with intra-abdominal
      visceral fat accumulation.
AB  - OBJECTIVE: To determine how lipoprotein lipase mass in the pre-heparin plasma is
      affected by body fat distribution, which is known to be closely related to lipid
      disorder, either directly or through insulin resistance. SUBJECTS: A total of 57
      subjects consisting of 50 hyperlipidemic and 7 normolipidemic subjects (age 54 +/
      IIy; 31 men, 26 women; body mass index 24+/- 2.5 kg/m2; serum total cholesterol
      6.4+/-1.5 mmol/l; triglycerides, 2.4 +/- 1.7 mmol/l; HDL-cholesterol 1.3 +/- 0.5
      mmol/l) were enrolled. MEASUREMENTS: We investigated the correlation between pre
      heparin plasma LPL mass and intra-abdominal visceral fat area (or subcutaneous
      fat area) evaluated by computed tomography, and serum lipids and lipoproteins.
      RESULTS: Pre-heparin plasma LPL mass correlated inversely against intra-abdominal
      visceral fat area (r = - 0.51, p < 0.0001) and body mass index (r = - 0.46, p =
      0.0003), but did not show any significant correlation with subcutaneous fat area.
      Pre-heparin plasma LPL mass had a positive correlation with serum high density
      lipoprotein cholesterol (r = 0.45, p = 0.0004) and a negative correlation against
      serum triglycerides (r = - 0.48, p = 0.0002). CONCLUSIONS: Pre-heparin plasma LPL
      mass is closely associated with intra-abdominal fat distribution, and the
      measurement of its value gives useful information concerning metabolic disorder.

PMID- 11507680
TI  - Relation between lean body mass and thyroid volume in competition rowers before
      and during intensive physical training.
AB  - OBJECTIVE: Lean body mass is a better determinant of thyroid size than body
      weight as demonstrated in a previous crosssectional study. We now evaluated if
      intra-individual changes in body composition and especially changes in lean body
      mass, due to physical training, could give rise to changes in thyroid volume.
      SUBJECTS AND METHODS: We investigated 17 freshmen (group 1) before and after six
      months of competition rowing; controls (group II) were 19 senior rowers, already
      participating in a training program for more than 2 years. RESULTS: In group I
      body weight (BW; p < 0.01), lean body mass (LBM; p < 0.05), fat weight (FW; p <
      0.05), body mass index (BMI; p < 0.01) and thyroid volume (TV; p = 0.08) all
      decreased; in group II body composition and thyroid volume did not change at all
      during the 6 months observation period. Whereas serum TSH and T3 did not change,
      free thyroxine (FT4) concentrations increased slightly in both groups (p < 0.01),
      presumably caused by the combination of exercise and insufficient energy intake.
      Taking together all subjects, baseline TV was directly related to BW (r = 0.35,
      p<0.05), to LBM (r=0.40, p<0.05) and to BMI (r=0.43, p < 0.01) but not to FW (r =
      - 0.06, NS). The decrease in thyroid volume was related to the decrease in LBM (r
      = 0.32, p = 0.05), in BW (r = 0.49, p < 0.005), in FW (r = 0.42, p = 0.01) and in
      BMI (r = 0.53, p = 0.001). CONCLUSIONS: After a six-month period of intensive
      physical training, changes in thyroid volume correlate directly with changes in
      body composition.

PMID- 11507679
TI  - The within-pair resemblance in serum levels of androgens, sex-hormone binding
      globulin and cortisol in female obese identical twins - effect of negative energy
      balance induced by very low-calorie diet.
AB  - The first aim of the present study was to evaluate the changes in serum levels of
      cortisol, testosterone, dehydroepiandrosterone (DHEA), dehydroepiandrosterone
      sulphate (DHEA-S) and sex hormone-binding globulin (SHBG) in response to weight
      loss induced by one month of treatment with a very low-calorie diet (VLCD) in
      twelve pairs of female obese monozygotic twins. The second aim of the study was
      to investigate any within-pair resemblance in serum levels of steroids and SHBG
      before and after a negative balance protocol, as well as the resemblance in
      changes in response to therapeutic weight loss. VLCD-induced weight loss of
      8.7+2.9 kg was associated with significant increases in serum testosterone
      (p<0.05) and SHBG (p<0.001) levels, whereas no significant changes in serum
      levels of cortisol, DHEA and DHEA-S were observed. Significant within-pair
      resemblances for both pre-treatment and post-treatment concentrations were
      revealed for DHEA-S (pre-treatment ICC = 0.795, p < 0.01, post-treatment ICC =
      0.712, p < 0.01) and for testosterone (pre-treatment ICC = 0.594, p <0.05, post
      treatment ICC = 0.735, p < 0.01). The baseline within-twin-pair resemblance in
      serum cortisol level at 7 a.m. (ICC=0.747, p < 0.05) was lost with VLCD
      treatment, while its concentration at 9 p.m. developed a within-pair similarity
      with weight loss (ICC = 0.824, p < 0.001). Similarly, VLCD treatment led to a
      significant within-pair resemblance in post-treatment level of DHEA (ICC = 0.755,
      p < 0.01), while no within-twin-pair resemblance was shown for either pre
      treatment or post-treatment SHBG levels. None of the hormones measured exhibited
      any within-pair resemblance in response to VLCD-induced energy deficit, except
      for serum cortisol levels. A significant within-twin-pair resemblance in the
      changes in serum cortisol levels at 7 a. m. (ICC = 0.789, F = 8.5, p < 0.001), at
      1 p.m. (ICC = 0.660, F = 4.9, p <0.01) and at 9 p.m. (ICC = 0.795, F = 8.8, p
      <0.001) were demonstrated even after adjustment for fat mass loss. An absence of
      any within-pair similarity was observed in both pretreatment and post-treatment
      levels of SHBG, while a significant within-pair resemblance in SHBG response to
      VLCD treatment (ICC = 0.658, p < 0.05) was recorded. We conclude that the
      significant within-twin-pair resemblance demonstrated for androgens and cortisol
      might suggest an important role for genetic factors in the regulation of their
      serum levels. Our results also suggest that the mechanisms controlling baseline
      levels of cortisol and SHBG differ from those influencing their responses to
      energy deficit induced by VLCD.

PMID- 11507681
TI  - Impaired non-esterified fatty acid suppression is associated with endothelial
      dysfunction in insulin resistant subjects.
AB  - In a recent study, we found a significant association between insulin resistance
      (IR) and disturbed flow-associated (endothelial-dependent) vasodilation in first
      degree relatives of subjects with type 2 diabetes. However, the mechanisms
      linking insulin resistance and endothelial dysfunction (ED) have not been fully
      elucidated. Experimental data have pointed out that non-esterified fatty acids
      (NEFA) have a modulating effect on NO-synthase activity, and therefore on
      endothelial function. The aim of our study was to evaluate whether insulin
      resistance associated impaired NEFA suppression is present in subjects with ED.
      We examined 53 first-degree relatives (FDR) of patients with type 2 diabetes
      (32f, 21 m, mean age 35 years). Endothelial function was measured as flow
      associated vasodilation (FAD%) of the brachial artery. Insulin sensitivity was
      evaluated with a standard hyperinsulinemic glucose clamp (insulin infusion rate
      of 1 mU/kg/min). While under fasting conditions, NEFA did not differ between
      groups with high or low FAD (0.415+/-0.033 vs. 0.394 +/- 0.040 mmol/l; p = n.
      s.), reduced FAD% was significantly associated with higher non-esterified fatty
      acids concentrations during steady state of the glucose clamp (0.072+/-0.022 vs.
      0.039+/-0.016mmol/l; p=0.04). This association was independent of insulin levels
      under fasting conditions and during the glucose clamp. In conclusion, our results
      reveal a significant association between endothelial dysfunction and impaired non
      esterified fatty acid suppression in insulin resistant subjects. As insulin
      resistance of lipolysis is a feature of the insulin resistance syndrome, these
      results suggest that elevated NEFA concentrations could play a role linking
      endothelial dysfunction and insulin resistance in vivo.

PMID- 11507682
TI  - Effect of the pattern of elevated free fatty acids on insulin sensitivity and
      insulin secretion in healthy humans.
AB  - In order to investigate whether the pattern of elevated free fatty acids (FFAs)
      has any effect on insulin sensitivity and insulin secretion in humans, we
      produced 2 distinct serum FFA patterns (PT 1 and 2) by infusing 6 healthy
      volunteers with 2 different lipid emulsions plus heparin for 24 hours. A
      hyperglycemic clamp (approx. 8 mM, 140 min) was performed before and 5 and 24
      hours after both lipid infusions to determine insulin sensitivity and insulin
      secretion simultaneously. Total FFAs had increased comparably by 24 hours (2020+/
      268 microM in PT 1) and (1812+/-154 microM in PT 2, p =0.24). Serum PT 1
      contained 66% saturated FFAs plus monoenes and 34% polyenes, while PT 2 contained
      80% saturated FFAs plus monoenes and 20% polyenes. Thus, the ratio of
      polyunsaturated to saturated plus monoenes was about 0.5 in PT 1 vs. 0.25 in PT
      2. In PT 1, the insulin sensitivity index (ISI) decreased by 20 +/- 7% and 27 +/-
      10% from basal after 5 and 24 hours, respectively. In PT 2, the ISI decreased
      significantly more after 5 (41+/-7%, p = 0.008) and 24 hours (52+/-6%, p =
      0.005). In contrast, different phases of insulin secretion did not change during
      the lipid infusion and did not vary between the two FFA profiles. In conclusion,
      these findings provide preliminary evidence that the composition of elevated
      serum FFAs influenced insulin sensitivity in humans. The FFA pattern low in
      polyunsaturated FFAs reduced insulin sensitivity more than the pattern high in
      polyunsaturated FFAs. In contrast, no effect on insulin secretion was observed.

PMID- 11507683
TI  - Release of beta-endorphin by prostaglandin E2 to lower plasma glucose in
      streptozotocin-induced diabetic rats.
AB  - In the present study, Wistar rats, which received a streptozotocin injection to
      induce diabetes (STZ-diabetic rats), a model similar to insulin-dependent
      diabetes mellitus (IDDM) or type 1 diabetes mellitus, were used to investigate
      the effect of prostaglandin (PG) E2 on plasma glucose. Intravenous injection of
      PGE2 produced a dose-dependent lowering of plasma glucose level in fasting STZ
      diabetic rats after 60 min. In addition to the blockade of this hypoglycemic
      effect by guanethidine (a noradrenergic nerve terminal-blocking agent), prazosin
      at a dose effective to block alpha1-adrenoceptors abolished the action of PGE2.
      An increase of plasma norepinephrine (NE) was also observed in STZ-diabetic rats
      receiving PGE2 injections. Participation of sympathetic stimulation by PGE2 may
      thus be speculated. Also, the plasma glucose-lowering effect of PGE2 was also
      blocked by pretreatment with naloxone or naloxonazine at doses sufficient to
      block opioid mu-receptor. Injection of PGE2 increased plasma beta-endorphin-like
      immunoreactivity (BER) in STZ-diabetic rats, and this action was abolished by
      prazosin. Bilateral adrenalectomy resulted in the loss of this PGE2 effect, and
      no increase was seen in plasma BER with PGE2 in STZ-diabetic rats. Therefore,
      beta-endorphin from the adrenal gland appears to be responsible for the lowering
      of plasma glucose in STZ-diabetic rats by PGE2 through an increase of NE release
      to activate alpha1-adrenoceptors.

PMID- 11507685
TI  - Usefulness of free sensate osteofasciocutaneous forearm and fibula flaps for
      neophallus construction.
AB  - Female-to-male transsexuals have been treated by the authors since the 1970's,
      using different operative methods. Since 1981, these patients have received
      neophallus construction with free sensate osteofasciocutaneous forearm flaps and,
      since 1993, with free sensate osteofasciocutaneous fibula flaps. In order to
      evaluate the usefulness of these flaps, the authors performed, in 24 patients (12
      with forearm and 12 with fibula flaps), the following examinations: clinical and
      radiologic evaluations of the neophallus and its donor site, as well as patient
      questionnaires. In all patients, subjective findings and clinical examinations
      showed no significant variations in neophallus size and form. Patients with
      fibula flaps had better sexual intercourse, although their neophallus sensibility
      was minor, when compared to the forearm flap patients. Donor-site morbidity was
      moderate in both groups. On radiologic examination, robust, calcified bone
      structure, and no fracture of the neophallus bone and its donor site, as well as
      no instability of the ankle joint (in the fibula flap patients) were found. These
      findings further support the use of these free sensate osteofasciocutaneous flaps
      for neophallus construction. In the authors' opinion, it is the patient who must
      decide which method should be used for neophallus construction.

PMID- 11507684
TI  - Autonomy of cortisol secretion in clinically silent adrenal incidentaloma.
AB  - Recent progress in non-invasive imaging techniques have resulted in an increasing
      frequency of adrenal incidentaloma discovery. In addition, even clinically silent
      adrenal tumor has been suggested to possess a subtle production of adrenal
      hormones. The aim of the study was to ascertain the autonomy of cortisol
      production in clinically silent adrenocortical incidentaloma. We investigated the
      hypothalamic-pituitary-adrenal axis in 38 patients with adrenal incidentaloma.
      Basal plasma cortisol level was reproducibly within normal range in all the
      patients with adrenal incidentaloma, but was also normal in half of the Cushing's
      syndrome cases studied. Eighteen of 38 patients showed plasma cortisol above 3
      microg/dl after 1 mg dexamethasone (Dex) and above 1 microg/dl after 8 mg Dex,
      respectively, and were defined as preclinical Cushing's syndrome. These patients
      were subjected to further evaluation of the autonomy of cortisol production. The
      incidence of positive findings indicating autonomy of cortisol secretion was as
      follows: suppressed basal plasma ACTH level in 44%, loss of normal diurnal rhythm
      in 79%, lack of ACTH response to CRF in 35%, decreased plasma DHEA-S level in
      28%, significant laterality of 131I-adosterol uptake in 75%, atrophy of the
      contralateral side of the adrenal on CT scan in 6%, and histological atrophy of
      the adjacent adrenal cortex in 56%, respectively. The endocrine feature relevant
      to the hypothalamic-pituitary-adrenal axis varied from patient to patient,
      ranging from the non-functioning adrenal adenoma to Cushing's syndrome. In
      addition, the results of each test did not coincide with others in each patient.
      These results clearly demonstrated that the incidence of autonomy of cortisol
      production in the clinically silent adrenal incidentaloma is not infrequent,
      showing significant diversity. Systemic evaluation of the hypothalamic-pituitary
      adrenal axis before adrenal surgery is warranted for an appropriate
      glucocorticoid replacement after adrenal surgery.

PMID- 11507686
TI  - Lateral thoracic artery as a vascular variant in the supply to the free serratus
      anterior flap.
AB  - The authors describe a case in which the dominant blood supply to a
      subperiosteally-harvested serratus anterior muscle and rib composite myoosseous
      free flap came from the lateral thoracic artery. There were no other associated
      features in this patient to warn of the vascular variant. Reconstructive surgeons
      should be aware of possible variations in the vascular anatomy of this flap.

PMID- 11507687
TI  - Microsurgical replantation of a totally amputated ear without venous repair.
AB  - The authors present a case of successful replantation of a totally avulsed ear in
      a 37-year-old patient, using a termino-terminal arterial anastomosis on the
      superficial temporal artery. As no suitable vein could be identified in the
      amputated part, they relied on leech therapy and systemic anticoagulation for
      venous drainage. Despite an 18-hr ischemia, the ear survived completely.

PMID- 11507688
TI  - Free temporoparietal fascial flap for coverage of a large palmar forearm wound
      after hand replantation.
AB  - A free temporoparietal fascial flap with a split-thickness skin graft was used to
      cover a large palmar forearm wound in a patient whose hand had been replanted 21
      days earlier after traumatic amputation at the distal forearm level. At a 39
      month follow-up, the patient had achieved an excellent cosmetic and functional
      result, with no alopecia or facial nerve injury. The flap is advantageous for
      coverage of wounds that require a large amount of thin, pliable tissue, and it
      leaves a concealed donor-site scar.

PMID- 11507689
TI  - Protective effects of vitamins A and E pretreatment in venous
      ischemia/reperfusion injury.
AB  - It has been suggested that venous ischemia is more injurious to tissue viability
      than is arterial ischemia of equivalent duration. The precise mechanism of tissue
      damage due to venous ischemia is still not well-determined. Current research has
      shown that it is multifactorial, and that lipid peroxides, prostanoid metabolism,
      and a free radical mechanism are the major contributors. Vitamins A and E are
      lipid-soluble vitamins that have been suggested to be successful in the treatment
      of arterial ischemia/reperfusion injury due to their antioxidant properties. In
      the present study, the authors examined the protective effects of vitamins A and
      E pretreatment on reperfusion injury induced by venous occlusion of rat
      epigastric island flaps based on an epigastric artery and vein pedicle. In the
      first part of the study, to determine critical ischemia time, epigastric island
      skin flaps (3 x 6 cm) were elevated on their vascular pedicles in 40 male Sprague
      Dawley rats. Total venous occlusion of the skin flap was produced by ligating all
      draining veins and clamping the epigastric vein. Arterial inflow was left intact.
      Rats were randomly assigned to five groups (n=8) for 2, 5, 7, 9, and 10 hr of
      venous ischemia. Despite the occurrence of widespread reperfusion injury, reflow
      was established (p<0.005) at 9 hr. In the second part of the study, 20 rats were
      randomly divided into four groups (n=5). The effects of vitamins A and E
      following 9 hr ischemia/reperfusion injury were examined. Rats were pretreated
      with vitamin E, vitamin A and vitamins A+E for 5 days. At the end of the fifth
      day, each rat had undergone an epigastric island skin flap and venous occlusion,
      as described above. Mean surviving flap area (percent) and plasma lipid peroxides
      (TBARs), total thiol content (t-SH), glutathione peroxidase (Gpx), and superoxide
      dismutase (SOD) were determined for each rat. Results suggest that, in the
      prevention of venous ischemia/reperfusion injury, vitamin A and vitamin E are not
      effective when used as single agents; however, when used in combination, they
      significantly increase surviving flap area by a synergistic effect.

PMID- 11507690
TI  - Free-tissue transfer experience at a county hospital.
AB  - As reimbursement for free-tissue transfer decreases, the authors find an increase
      in the number of free flaps performed at their county facility. Over 60 percent
      of the free flaps performed during the past 10 years were completed within the
      last 4 years. This influx of patients prompted a review of their experience with
      free-tissue transfer. This retrospective study of the free-flap experience at a
      county hospital reviewed 49 patients with 53 free flaps between 1991 and 1999.
      Forty-five free flaps (85 percent) were successful, with an overall failure rate
      of 15 percent. Most free flaps were performed on traumatic wounds. Risk factors,
      such as smoking, diabetes, and peripheral vascular disease, did not reliably
      predict free-flap failure. Irradiated, chronic wounds were associated with the
      highest failure rates. Seventy-five percent of the free-flap failures were due to
      delayed return to the operating room, once the flap appeared compromised. Delay
      in reexploration resulted in a zero salvage rate. Prompt recognition of failed
      flaps and emergent exploration will improve the success rate.

PMID- 11507691
TI  - Tattooing agents for nerve marking in experimental surgery.
AB  - Experimental nerve surgery involves test procedures, including those for nerve
      lesions in continuity, that leave no visible traces of impairment after surgery.
      In such cases, non-resorbable sutures are usually used to mark the lesion sites
      on the nerves. However, this method has two drawbacks: it is not completely
      atraumatic, and may be frustrating due to displacement of the suture material.
      The authors demonstrate the use of carbon tattoo pigment to mark nerve lesions
      permanently, thus allowing their identification reliably at any later date.
      Following successful preliminary experiments, the tattooing procedure was used in
      12 New Zealand White rabbits that had been operated on for a specific nerve
      regeneration problem. Altogether, 56 tattoo marks were set. The small pigment
      spots were well-preserved and clearly visible during a second and third operation
      4 and 15 weeks later. Histologic examination identified the carbon granules in
      the outer epineurium; there were no signs of inflammation. This simple,
      atraumatic, inert, and permanent method for nerve markings in the experimental
      animal is recommended.

PMID- 11507692
TI  - A new animal model for tissue preservation.
AB  - In vivo preservation of tissues may exist as a problem in experimental and
      clinical research. Adipose tissue, nerves, and vessels are the tissues that are
      usually preserved in vivo for future use or for the evaluation of results in
      experimental research. Limited volume and difficult conditions in such areas in
      animal models usually create disappointing results, because of the difficulty in
      distinguishing the experimental from the surrounding tissues; the insufficiency
      of the volume of space; and the lack of compliance in animals. A new rat model
      for in vivo preservation studies is described. A muscular pocket designed between
      the external and internal oblique muscles is a good choice as an animal model for
      tissue preservation in plastic surgery research.

PMID- 11507693
TI  - Quantification of nerve tension after nerve repair: correlations with nerve
      defects and nerve regeneration.
AB  - This study tested the validity of a quantitative in vitro nerve-tension-measuring
      technique, by correlating the tension measurements with functional and
      morphologic assessments of nerve regeneration. Initially, harvested nerves were
      used in vitro to determine a K value for lateral displacement in this tissue.
      Next, this value was used to calculate the tension of nerve repair, following 0-,
      3-, 6-, and 9-mm resections of nerves in groups of rats. After quantifying the
      nerve tensions following excision and repair, the authors determined a sciatic
      function index to evaluate functional recovery and axon diameter in the animals.
      Functional recovery was significantly impaired in animals with elevated
      measurable tension (9.04 +/- 0.74 g in a 6-mm defect, 27.76 +/- 8.86 g in a 9-mm
      defect), compared to animals with no or 3-mm excision and measured tension of 3.3
      +/- 1.09 g or less. Increased tension was also associated with a significant
      decrease in axon diameter. This study succeeded, therefore, in quantitatively
      relating the elements of measured nerve tension, nerve gaps, functional nerve
      recovery, and morphologic regeneration. Quantification of nerve tension by
      lateral displacement in vivo offers a possible solution to clinical management of
      nerve gaps, when the choice between primary repair and nerve grafting is not a
      clear one.

PMID- 11507695
TI  - Longitudinal analysis of histologic high-grade disease after negative cervical
      cytology according to endocervical status.
AB  - BACKGROUND: There is concern that Papanicolaou (Pap) smears without an
      endocervical component may be associated with the incomplete detection of
      abnormalities. METHODS: Four cohorts of women with initial negative Pap smear
      reports and an additional Pap smear obtained within 36 months were established
      from a statewide database. The endocervical status of the entry smear and
      subsequent smears, respectively, among the cohort women was as follows: Cohort A:
      present and present; Cohort B: absent and present; Cohort C: present and absent;
      and Cohort D: absent and absent. The subsequent incidence of histologic high
      grade disease was calculated for each cohort. RESULTS: No significant differences
      were evident in the incidence of histologic high-grade disease between Cohorts A
      and B (standardized incidence ratio for Cohort B compared with Cohort A = 0.89;
      95% confidence interval, 0.67-1.12). Cohorts C and D had significantly less high
      grade disease compared with Cohorts A and B. CONCLUSIONS: The findings of the
      current study indicate that early repeat testing of women whose Pap smears are
      negative but lack an endocervical component is not justified because no higher
      rate of histologic high-grade abnormality was evident on longitudinal follow-up
      even when later smears included an endocervical component.

PMID- 11507694
TI  - Seven regions of the genome show evidence of linkage to type 1 diabetes in a
      consensus analysis of 767 multiplex families.
AB  - Type 1 diabetes (T1D) is a genetically complex disorder of glucose homeostasis
      that results from the autoimmune destruction of the insulin-secreting cells of
      the pancreas. Two previous whole-genome scans for linkage to T1D in 187 and 356
      families containing affected sib pairs (ASPs) yielded apparently conflicting
      results, despite partial overlap in the families analyzed. However, each of these
      studies individually lacked power to detect loci with locus-specific disease
      prevalence/sib-risk ratios (lambda(s)) <1.4. In the present study, a third genome
      scan was performed using a new collection of 225 multiplex families with T1D, and
      the data from all three of these genome scans were merged and analyzed jointly.
      The combined sample of 831 ASPs, all with both parents genotyped, provided 90%
      power to detect linkage for loci with lambda(s) = 1.3 at P=7.4x10(-4). Three
      chromosome regions were identified that showed significant evidence of linkage
      (P<2.2x10(-5); LOD scores >4), 6p21 (IDDM1), 11p15 (IDDM2), 16q22-q24, and four
      more that showed suggestive evidence (P<7.4x10(-4), LOD scores > or =2.2), 10p11
      (IDDM10), 2q31 (IDDM7, IDDM12, and IDDM13), 6q21 (IDDM15), and 1q42. Exploratory
      analyses, taking into account the presence of specific high-risk HLA genotypes or
      affected sibs' ages at disease onset, provided evidence of linkage at several
      additional sites, including the putative IDDM8 locus on chromosome 6q27. Our
      results indicate that much of the difficulty in mapping T1D susceptibility genes
      results from inadequate sample sizes, and the results point to the value of
      future international collaborations to assemble and analyze much larger data sets
      for linkage in complex diseases.

PMID- 11507696
TI  - Estimating the percentage of Papanicolaou smears that can be reproducibly
      identified: modeling Papanicolaou smear interpretation based on multiple blinded
      rescreenings.
AB  - BACKGROUND: Multiple blinded rescreenings of Papanicolaou (Pap) smears for
      litigation purposes is based on the assumption that a subset of Pap smears can be
      reproducibly identified. The size of this subset is not known. METHODS: To
      estimate the size of the subset of Pap smears that can be reproducibly
      identified, a model was constructed based on the results of repeated blinded
      screenings in the AutoPap Primary Screening System Trial. Additional analysis
      came from data in the literature. RESULTS: Routine and AutoPap-assisted screening
      both have a detection rate for all detected abnormal cases of < 50%. Models with
      only two subsets or types of slides each with a different detection rate
      correlated well with the available data. Data from multiple rapid reviews
      strongly supported the existence of additional definable subsets. Although the
      percentage of cases with an expected detection rate of 100% in a three-subset
      model might have been as high as 30% of the abnormal cases detected in a single
      review, all estimates that included a second subset of slides with at least a 50%
      detection rate limited the percentage of slides in the 100% sensitive subset of
      slides to < 2% of all abnormal slides and < 6% of all abnormal slides detected by
      a single screening. CONCLUSIONS: Repeated screenings of Pap smears allowed more
      accurate models of the sensitivity of Pap-smear screening and the overall
      incidence of abnormal cases. The data strongly supported the existence of
      multiple subsets of Pap smears, which can be defined by repeated blinded
      rescreenings. The percentage of slides that can be reproducibly identified was
      small.

PMID- 11507697
TI  - Fine-needle aspiration of epithelioid sarcoma: cytology findings in nine cases.
AB  - BACKGROUND: Epithelioid sarcoma is a rare tumor with characteristic morphologic
      and immunohistochemical features. It can be confused histologically and
      cytologically with a variety of benign and malignant lesions, including a
      granulomatous process, synovial sarcoma, melanoma, squamous cell carcinoma, and
      adenocarcinoma. The objective of this study was to define the cytologic features
      of this rare tumor. METHODS: The cytologic features of nine histologically
      confirmed epithelioid sarcomas were analyzed. The criteria evaluated included
      cell size and shape, cell borders, cluster organization, cytoplasmic
      characteristics, nuclear and nucleolar features, and background characteristics.
      RESULTS: In most cases, single, dispersed cells represented the predominant
      pattern, with only a few small clusters present. The cells were mostly round with
      interspersed spindle cells and mild to moderate pleomorphism. The nuclei were
      large and eccentrically located, with a plasmacytoid appearance. A pale zone in
      the perinuclear area was evident in three of nine cases. Well-defined cell
      borders with intercellular spaces between malignant cells were observed in eight
      cases. In three cases, a granuloma-like structure was identified. In two cases,
      the cells were mostly spindle and showed greater cellular pleomorphism.
      CONCLUSION: Epithelioid sarcoma is an uncommon tumor with a wide range of
      differential diagnoses, especially in cytology specimens. Awareness of its
      existence and knowledge of its cytologic features are important for a correct
      diagnosis.

PMID- 11507698
TI  - Fine-needle aspiration features of pilomatrixoma.
AB  - BACKGROUND: Pilomatrixoma (PMX) is a benign skin neoplasm of hair matrix origin.
      The fine-needle aspiration (FNA) features of PMX frequently lead to a
      misdiagnosis of carcinoma. METHODS: Nine cases of PMX in which a preoperative FNA
      was performed were reviewed. The cytologic features were compared with the
      histologic appearance of corresponding surgical specimens as well as with
      cytologic features of tumors that arose in the differential diagnosis. RESULTS:
      Unequivocal benign diagnoses were rendered in three cases; the correct
      preoperative diagnosis of PMX was rendered in two of these cases and considered
      in an additional case. In four additional cases, carcinoma was diagnosed or could
      not be excluded. A noncommittal diagnosis of epithelial tumor, most likely of
      skin adnexal origin, was rendered in an additional single case. Retrospective
      review of the FNA smears in all nine instances disclosed cytologic features that
      corresponded well with the histologic components of PMX. Diagnostic cytologic
      features included cellular aspirates; clusters of small, primitive-appearing
      basaloid epithelial cells; a high nuclear-cytoplasmic ratio; evenly dispersed
      chromatin; prominent nucleoli; pink, fibrillary material enveloping clusters of
      basaloid cells; multinucleated giant cells; and sheets of ghost cells.
      CONCLUSIONS: The FNA cytologic diagnosis of PMX may be extremely difficult; its
      distinction from various primary cutaneous carcinomas is most problematic.
      Recognition of a unique constellation of cytologic features in FNA smears in the
      appropriate clinical context is most helpful in making this distinction.

PMID- 11507699
TI  - Soft tissue masses in patients with multiple myeloma: a fine-needle aspiration
      study of 30 cases with flow cytometry and clinical correlation.
AB  - BACKGROUND: To the authors' knowledge, the prognostic significance of plasma cell
      cytology in soft tissue (ST) masses from patients with multiple myeloma (MM) is
      unknown. Myeloma patients usually are monitored by bone marrow (BM) aspirates and
      biopsies to assess plasma cell differentiation, tumor burden, and response to
      treatment. Monitoring of ST lesions by fine-needle aspiration (FNA) is not
      performed routinely. The objective of the current study was to examine ST masses
      in MM patients using FNA and to classify and determine the prognostic
      significance of MM in these lesions based on cytologic features. METHODS: FNAs of
      30 ST masses from 27 patients with a history of MM were examined for disease
      involvement. In the patients with MM, the cytologic features were evaluated and
      the lesions were graded as low grade, intermediate grade, or high grade based on
      the classification of Bartl et al. for MM in BM specimens. Concurrent BM samples
      as well as cytogenetic and flow cytometric results also were reviewed. RESULTS:
      Twenty-seven of the FNA specimens (90%) were positive for MM, and three specimens
      (10%) were negative (one case each of lipoma, keratinous cyst, and
      aspergillosis). Among the MM cases, 5 (18.5%) were low grade, 15 (55.6%) were
      intermediate grade, and 7 (25.9%) were high grade (blastic MM). Simultaneous BM
      involvement was present in 23.5% of low-grade MM (4 of 17 cases), 35.3% of
      intermediate-grade MM (6 of 17 cases), and 71% of high-grade MM (5 of 7 cases).
      Clinically, 10 of 24 patients (42%) died within 9 months (median, 2 months).
      Patients with high-grade myeloma (blastic MM) in ST masses appeared to have worse
      survival; 43% (3 of 7 patients) died by a median time of 2 months, compared with
      12% of patients with low-grade and intermediate-grade MM (2 of 17 patients).
      CONCLUSIONS: FNA of ST masses appears to improve the management of MM patients by
      providing diagnostic material, samples for ancillary studies, and prognostic
      information. ST MM can be classified reliably into grades of prognostic
      significance utilizing the classification of Bartl et al. Intermediate-grade MM
      was the most frequent subtype present in ST masses.

PMID- 11507700
TI  - Diagnostic accuracy of fine-needle aspiration biopsy is determined by physician
      training in sampling technique.
AB  - BACKGROUND: Fine-needle aspiration biopsy (FNAB) has been used with variable
      success as a diagnostic test for benign and malignant breast lesions. The goal of
      this study was to examine the effects of training physicians in the fine-needle
      aspiration sampling-technique on the diagnostic accuracy of FNAB of palpable
      breast masses. The settings for this study were private physicians' offices and
      university clinics of primary care physicians, surgeons, and cytopathologists.
      METHODS: We reviewed 1043 consecutive FNAB specimens of the breast obtained
      during 1 year (1992): 729 FNABs were performed by formally trained physicians (at
      least 150 FNABs performed previously under supervision during fellowship training
      or the equivalent) who had done at least 100 FNABs during the year; 314 FNABs
      were performed by physicians without formal training who had done a median of
      only 2 FNABs during the year (range, 1-43 FNABs). All FNAB specimens were
      reviewed microscopically and evaluated for cellularity and type of material
      present, for diagnostic accuracy, and for the rate of surgical intervention. A
      minimum of 2 years of follow-up was obtained by matching all cases to the
      population-based Northern California Cancer Registry. FNAB specimens were
      correlated with histologic specimens when they were available. RESULTS: Using
      FNAB, the formally trained physicians missed 2% of cancers, whereas the
      physicians without formal training missed 25%. Among the patients with benign
      lesions seen by the formally trained physicians, 8% went on to surgery, whereas
      30% of those seen by physicians without formal training did so. Specimens
      obtained by the formally trained physicians were significantly more cellular and
      were significantly less likely to be nondiagnostic. CONCLUSIONS: FNAB, when
      performed by physicians who are well trained in the technique, is a highly
      accurate, cost-effective diagnostic method that carries minimal morbidity and
      could replace a large number of surgical biopsies. When performed by physicians
      without adequate training, FNAB is often misleading and potentially harmful.

PMID- 11507701
TI  - Fine-needle aspiration biopsy diagnosis of gastrointestinal stromal tumors using
      morphology, immunocytochemistry, and mutational analysis of c-kit.
AB  - BACKGROUND: Differentiating gastrointestinal stromal tumors (GISTs) from other
      intramural mesenchymal tumors of the GI tract on fine-needle aspiration biopsies
      (FNABs) is difficult. Recent studies have shown that GISTs are
      immunophenotypically and genetically distinct. GISTs exhibit consistent
      immunohistochemical expression of CD-117 (KIT) and often express activating
      mutations of this protooncogene. The aim of the current study was to employ
      immunocytochemistry and mutational analysis of the c-kit gene to aid in the
      diagnosis of GISTs on FNAB. METHODS: Five endoscopic ultrasound-guided FNABs of
      gastrointestinal spindle cell neoplasms performed at the Veterans Affairs Medical
      Center (VAMC) in Portland, Oregon, from 1998-1999 were reviewed. A panel of
      immunocytochemical stains was performed on each cellblock including CD-117 (KIT),
      smooth muscle actin (SMA), desmin, S-100, and CD34. Genomic DNA (gDNA) was
      extracted, and amplification of exons 9, 11, 13 and 17 of c-kit was performed by
      polymerase chain reaction (PCR) on CD-117 (KIT) and CD34 positive cases. Direct
      sequencing of amplicons identified the mutations. RESULTS: Five patients were
      diagnosed with GISTs based on morphology and immunocytochemical positivity for CD
      117 and CD34. PCR analysis of c-kit exon 11 revealed three cases with novel-sized
      PCR bands in addition to the expected wild-type-sized PCR product. Amplicons from
      these cases contained an in-frame deletion mutation. One of the two cases with
      wild-type-;sized exon 11 amplicons was found to be heterozygous for a point
      mutation producing an amino acid substitution (W557R). No mutations in exon 9,
      11, 13, or 17 of c-kit were found in the remaining case. CONCLUSIONS: Ancillary
      techniques such as immunocytochemistry and c-kit gene mutational analysis may aid
      in the diagnosis of GISTs on FNABs.

PMID- 11507702
TI  - Cytologic diagnosis of gastrointestinal stromal tumor with emphasis on the
      differential diagnosis with leiomyosarcoma.
AB  - BACKGROUND: Gastrointestinal stromal tumor (GIST) has only recently been
      distinguished histologically and immunochemically from morphologically similar
      neoplasms of the abdomen. METHODS: The authors reviewed 15 cytologic cases of
      GIST (14 fine-needle aspiration [FNA] specimens and 1 peritoneal fluid specimen)
      and compared them with 23 cases of leiomyosarcoma (LMS) arising in the abdomen or
      pelvis (all FNAs). Immunochemistry (IC) was performed on both the cytologic and
      subsequent tissue specimens if sufficient specimen was available. RESULTS:
      Cytologic samples of GISTs typically showed irregularly outlined clusters of
      uniform spindle cells that were spread easily without crush artifact. The cells
      had wispy cytoplasm with long, delicate, filamentous extensions (13 cases; 87%).
      A prominent vascular pattern was common (9 cases; 60%); pleomorphism (1 case; 7%)
      was uncommon. The LMSs showed three-dimensional, tightly cohesive, sharply
      marginated syncytia of spindle cells, often with nuclear crush artifact. The
      cytoplasm/stroma had a distinct wiry, refractile appearance (21 cases; 91%);
      delicate filamentous cytoplasmic extensions (5 cases; 22%) and prominent vessels
      (3 cases; 13%) were less common. LMSs more commonly exhibited pleomorphism (14
      cases; 61%). Epithelioid cytomorphology, mitoses, and necrosis occasionally were
      observed in both tumor types. IC for c-kit (on cytologic material) was positive
      in 10 of 10 cases of GIST (usually diffuse and strong) and 2 of 19 cases of LMS
      (focal). CD34 positivity favored GIST (4 of 9 cases) over LMS (1 of 19 cases).
      Smooth muscle actin was positive in 20 of 20 LMSs (strong and diffuse) and 6 of
      10 GISTs (usually focal). Desmin was positive in 12 of 20 LMSs and was only
      focally positive in 1 of 11 GISTs. Correlation of IC results was excellent
      between cytologic and tissue specimens. CONCLUSIONS: Delicate cytoplasmic
      processes; a prominent vascular pattern; a lack of nuclear pleomorphism; and a c
      kit-positive, desmin-negative immunoprofile are characteristic features of GIST
      and help distinguish these tumors from LMS in cytologic specimens.

PMID- 11507703
TI  - Diagnostic value of hepatocyte paraffin 1 antibody to discriminate hepatocellular
      carcinoma from metastatic carcinoma in fine-needle aspiration biopsies of the
      liver.
AB  - BACKGROUND: Diagnosing liver tumors by fine-needle aspiration biopsy is safe and
      accurate. However, there are cases that prove diagnostically difficult.
      Traditionally, immunostains for alpha-fetoprotein and polyclonal carcinoembryonic
      antigen have been used to distinguish adenocarcinomas from hepatocellular
      carcinomas (HCCs). In poorly differentiated tumors, these immunostains have
      limitations in both sensitivity and specificity. An hepatocyte-specific
      immunostain has been described in the surgical pathology literature. To the
      authors' knowledge, this hepatocyte antibody has not been studied in liver fine
      needle aspiration biopsies. The authors examined the Hepatocyte Paraffin 1 (HP1)
      antibody for its diagnostic utility in this cytologic setting. METHODS: Cell
      block material from 40 cases of HCC and 53 cases of metastatic adenocarcinoma
      were studied. Slides were stained for HP1 by the avidin-biotin complex method
      following antigen retrieval. The percentage of malignant cells that exhibited
      coarse granular staining in the cytoplasm was estimated for all cases of HCC,
      poorly differentiated HCC, and metastatic adenocarcinoma. RESULTS: HP1 was
      expressed in 83% of all HCCs but in only 56% of poorly differentiated HCCs. Only
      2 of 53 (4%) of metastatic tumors expressed HP1. The overall sensitivity of HP1
      was 79% and its specificity was 96%. CONCLUSION: HP1 was found to be a specific
      immunostain that may prove helpful in diagnosing all but the most
      undifferentiated liver tumors biopsied by fine-needle aspiration.

PMID- 11507704
TI  - Developmental changes in responsivity to threat are stimulus-specific in rats.
AB  - During early ontogeny, stimuli that pose a threat to an animal change. Unrelated
      adult male rats may kill young rats, but infanticide ends around weaning.
      Predation, on the other hand, may increase during early ontogeny when rats begin
      to extend their activity range. We investigated the developmental course of two
      defensive responses, immobility and analgesia, in young rats exposed to an adult
      male rat or to predator cues. Preweaning 14-day-old rats became immobile and
      analgesic when exposed to the male and showed immobility but not analgesia when
      exposed to cat odor. On Day 26, around weaning, the presence of the male rat no
      longer induced immobility and analgesia whereas cat odor produced higher levels
      of immobility and analgesia compared to control and male-exposed animals. This
      developmental change in responsivity may reflect the differences in the risk of
      being harmed by a male or a cat during different periods of ontogeny.

PMID- 11507705
TI  - Ontogenetic differences in the effects of unpaired stimulus preexposure on
      eyeblink conditioning in the rat.
AB  - Learned irrelevance (LIr) is a Pavlovian conditioning phenomenon in which random
      or unpaired preexposure to a conditional stimulus (CS) and to an unconditional
      stimulus (US) retards subsequent paired conditioning involving these stimuli. A
      previous developmental study of eyeblink conditioning in the rat suggested that
      LIr is not present on postnatal Day 20. Stanton, Fox, and Carter (1998) showed
      that unpaired preexposure to a CS and a US on postnatal Day 17 failed to retard
      (and, in fact, facilitated) subsequent paired conditioning involving these
      stimuli on postnatal Day 20. The present experiments were designed to further
      characterize the ontogeny of this phenomenon. In Experiment 1, LIr was observed
      when rat pups were tested for eyeblink conditioning as described in Stanton et
      al. (1998), except that preexposure occurred on postnatal Day 27, and acquisition
      testing occurred on postnatal Day 30. In Experiment 2, preexposure and
      acquisition both occurred on postnatal Day 30, and four types of preexposure were
      compared: chamber only, CS alone, US alone, or unpaired presentation of CS and
      US. Unpaired preexposure impaired acquisition relative to that of the remaining
      three groups, which did not differ. Experiment 3, showed that under the
      conditions of Experiment 2, LIr failed to appear on postnatal Day 20, but was
      observed on postnatal Days 25 and 30. These findings suggest that learning that
      events are unrelated emerges between postnatal Days 20 and 25 in the rat.
      Possible behavioral and neural mechanisms underlying this effect are discussed.

PMID- 11507706
TI  - Maternally separated rats show deficits in maternal care in adulthood.
AB  - Although there is considerable research on the phenomenology, neuroendocrinology,
      neuroanatomy, and sensory control of maternal behavior, little is known about the
      influences of early postnatal and postweaning experiences on the development of
      maternal behavior. The purpose of this study was to assess how early life
      separation from the mother rat affects development of the offspring's juvenile
      and adult maternal behavior. From postnatal Days 1 to 17, 3 female rats within
      each litter were separated (SEP) from the mother and the rest of the litter for 5
      hr daily while 3 of their sisters were not maternally separated (NSEP). On
      postnatal Day 21, all subjects were weaned and randomly assigned to one of three
      juvenile conditions. One female from both SEP and NSEP groups was either isolated
      (I), given a social conspecific (S), or given 1- to 4-day-old pups (P) for 5
      consecutive days. Maternal behavior of SEP and NSEP animals was assessed and
      recorded on each of the 5 days. Once all animals reached adulthood, they were
      mated, gave birth, and were assessed for their maternal behavior. We found that
      the effects of maternal separation on juvenile maternal-like behaviors were
      minimal. On the other hand, maternal separation reduced adult maternal licking
      and crouching over pups. In addition, there was a significant interaction between
      postnatal and juvenile experience on maternal crouching in maternal animals.
      These results are discussed in terms of the variety of possible behavioral,
      endocrine, and neurochemical mechanisms that mediate the effects of early life
      experiences on adult maternal behavior.

PMID- 11507707
TI  - Cardiovascular responses to pacifier experience and feeding in newborn infants.
AB  - This study examined the effects of sucking on a pacifier immediately before
      feeding on cardiovascular responses to feeding. Twenty-eight bottle-feeding
      infants were studied at 12 to 40 hr of age. Blood pressure and heart rate
      measurements were made during three periods: Period 1-while infants rested in
      their cribs before a regularly scheduled feeding, Period 2-while being held by
      the feeder immediately before feeding, and Period 3-during the first 3 to 5 min
      of feeding. Half of the infants were given a pacifier during Period 2. Blood
      pressures and heart rates increased across the periods; however, increases in
      systolic blood pressure during feeding were reduced for the group of infants
      given a pacifier prior to feeding. We suggest that cardiovascular responses to
      feeding in infants are comprised of multiple elements. Most of the systolic blood
      pressure responses to feeding are elicited by sucking whereas the heart rate
      response is dependent on both sucking and nutrient intake.

PMID- 11507708
TI  - Response of adolescent bonnet macaques to an acute fear stimulus as a function of
      early rearing conditions.
AB  - When primate infants are reared during the first half-year of life in an
      environment in which their mothers face uncertain requirements for food
      procurement (variable foraging demand [VFD]), long-lasting behavioral and
      neurodevelopmental consequences ensue, including increases in timidity and social
      subordinance as well as alterations in stress-related neuroendocrine profiles. We
      examined the nature and persistence of the effects of VFD rearing by exposing VFD
      reared and normally reared adolescent bonnet macaques to a mild fear-provoking
      stimulus 2 years after the end of differential rearing. VFD-reared subjects at
      baseline were less gregarious than normally reared monkeys. VFDs also were
      considerably less responsive to the fear stimulus, and their behavior and affect
      returned to baseline levels more quickly than normally reared subjects. The
      extent and persistence of the sequelae of VFD rearing suggest parallels with
      predisposing factors in human anxiety disorders.

PMID- 11507709
TI  - Social rearing conditions before weaning influence numbers and proportions of
      blood immune cells in laboratory rats.
AB  - The influence of the early social rearing environment on blood cellular immunity
      was investigated in the male offspring of Long-Evans rats. Sons of females housed
      in pair groups (P-males) and sons of females living in a mixed sex colony (C
      males) were studied. After weaning at the age of 21 days, offspring were housed
      individually to ensure identical experiences until the age of 100 days when
      immunological assessments were conducted. C-males had significantly higher
      numbers of blood CD4 and CD8 T cells as well as higher numbers of granulocytes
      and monocytes than P-males. In contrast, the number of B cells and NK cells was
      similar in P- and C-males. T-cell responsiveness to ConA, determined in the
      peripheral blood mononuclear cells and whole blood assays, did not differ
      significantly between the two groups. The study indicates that the early social
      environment affects numbers and proportions of many blood immune cell subsets in
      later life.

PMID- 11507710
TI  - Human handling might interfere with conspecific recognition in the european
      rabbit (Oryctolagus cuniculus).
AB  - Handled rabbit pups react with decreased fear to a human at weaning. We
      hypothesized that pups learn species-specific features of their handler.
      Experiment 1 showed that handled animals' reactions were similar to both a human
      and their mother. Experiment 2 showed that pups reacted similarly to their mother
      and other adult rabbits. In Experiment 3, we used nonhandled control pups, and
      pups in the experimental groups were stimulated either by a human, a cat, or
      both. Only human-handled animals showed high affinity to approach a human at
      weaning. Similarly, only rabbit pups exposed to a cat did not show fear reaction
      towards a cat. Nonhandled controls avoided both the cat and the human, and
      rabbits stimulated by both species did not avoid any of them at weaning. We
      demonstrated that handling affected the behavior of weanling rabbits in a
      selective manner, as they only approached those objects frequently to which they
      had been exposed to.

PMID- 11507712
TI  - Fluorogenic and fluorescent labeling reagents with a benzofurazan skeleton.
AB  - Fluorogenic and fluorescent labeling reagents having a benzofurazan (2,1,3
      benzoxadiazole) skeleton such as 4-fluoro-7-nitro-2,1,3-benzoxadiazole (NBD-F), 4
      N,N-dimethylaminosulfonyl-7-fluoro-2,1,3-benzoxadiazole (DBD-F), 4-aminosulfonyl
      7-fluoro-2,1,3-benzoxadiazole (ABD-F), ammonium 7-fluoro-2,1,3-benzoxadiazole-4
      sulfonate (SBD-F), 4-hydrazino-7-nitro-2,1,3-benzoxadiazole (NBD-H), 4-N,N
      dimethylaminosulfonyl-7-hydrazino-2,1,3-benzoxadiazole (DBD-H), 4-nitro-7-N
      piperazino-2,1,3-benzoxadiazole (NBD-PZ), 4-N,N-dimethylaminosulfonyl-7-N
      piperazino-2,1,3-benzoxadiazole (DBD-PZ), 4-(N-chloroformylmethyl-N-methyl)amino
      7-N,N-dimethylaminosulfonyl-2,1,3-benzoxadiazole (DBD-COCl) and 7-N,N
      dimethylaminosulfonyl-4-(2,1,3-benzoxadiazolyl) isothiocyanate (DBD-NCS) are
      reviewed in terms of synthetic method, reactivity, fluorescence characteristics,
      sensitivity and application to analytes.

PMID- 11507713
TI  - Amino acid sequence and D/L-configuration determination methods for D-amino acid
      containing peptides in living organisms.
AB  - D-amino acid-containing peptides with biological activities have been isolated
      from invertebrates and amphibians, and partial racemization of amino acid
      residues in mammalian peptides associated with aging and diseases have been
      discussed. Here, we review the amino acid configuration determination methods in
      these peptides and recent progress of simultaneous determination method for
      sequence and configuration of amino acid residues. The applicability of C
      terminus sequence analysis and mass spectrometry to configuration determination
      of amino acids is also discussed.

PMID- 11507714
TI  - High-performance liquid chromatographic assay for glucuronidation activity of 7
      ethyl-10-hydroxycamptothecin (SN-38), the active metabolite of irinotecan (CPT
      11), in human liver microsomes.
AB  - A simple and sensitive assay for glucuronidation activity of 7-ethyl-10
      hydroxycamptothecin (SN-38), the active metabolite of irinotecan (CPT-11), in
      human liver microsomes by high-performance liquid chromatography (HPLC) with
      fluorescence detection is reported. The method was validated for the
      determination of SN-38 glucuronide (SN-38G) with respect to specificity,
      linearity, recovery, stability, precision, accuracy, and limits of detection and
      quantitation. There was no interference from matrix and non-enzymatic reactions.
      The calibration curve for SN-38G was linear from 5 to 500 nM. Average recoveries
      ranged from 98 to 100% in spiked human liver microsome samples, and the SN-38G
      was stable at 4 degrees C for at least 72 h. The newly developed method was found
      to be more sensitive and selective than previous methods using thin layer
      chromatography and HPLC. The limit of quantitation for SN-38G was 5 nM (2.5
      pmol/assay). The intra- and inter-day precision and accuracy were less than 7 and
      4%, respectively. The intra- and inter-day precision of enzyme assay for UDP
      glucuronosyltransferase (UGT) activity toward SN-38 in human liver microsomes was
      less than 4%. With this improved sensitivity, the kinetics of SN-38
      glucuronidation in human liver microsomes could be determined more precisely.
      Therefore, this method is applicable to in vitro study on the side effects and
      drug interactions of CPT-11 using small amounts of biological sample.

PMID- 11507715
TI  - Development of predictive retention-activity models of butyrophenones by
      biopartitioning micellar chromatography.
AB  - The predictive and interpretative capability of quantitative chromatographic
      retention-biological activity models is supported by the fact that in adequate
      experimental conditions the solute partitioning into the chromatographic system
      can emulate the solute partitioning into lipid bilayers of biological membranes,
      which is the basis of drug and metabolite uptake, passive transport across
      membranes and bioaccumulation. The use of retention data obtained in
      biopartitioning micellar chromatography (BMC) has been demonstrated to be helpful
      in describing the biological behaviour of different kinds of drugs. In this
      chromatographic system, polioxyethylene 23 lauryl ether Brij35 micellar mobile
      phases and C(18) reversed stationary phase in adequate experimental conditions
      are used. The RP-HPLC capacity factors of butyrophenones were determined using
      different Brij35 concentrations as micellar mobile phases. Relationships between
      seven biological activities of butyrophenones reported in bibliography and
      retention data were established and their predictive and interpretative ability
      evaluated. These relationships were significant between preclinical pharmacology
      and therapeutic efficacy parameters and the retention factors of butyrophenones
      (0.89 < R(2) < 0.98). The results indicate that the retention of compounds in BMC
      is capable of describing and predicting in vitro the biological activities of
      butyrophenones. This approach can be very useful in the development of new
      neuroleptic drugs, avoiding the use of experimental animals.

PMID- 11507716
TI  - Separation and quantification of paraquat and diquat in serum and urine by
      capillary electrophoresis.
AB  - The use of capillary electrophoresis (CE) for simultaneous qualitative and
      quantitative detection of paraquat (PQ) and diquat (DQ) in both serum and urine
      was investigated. The two herbicides were extracted from biological fluids with
      liquefied phenol. Serum required a deproteinization with chloroform and ammonium
      sulfate as pretreatment. The extracts were hydrodynamically injected and the
      complete separation was carried out in 10 min, using a capillary tube (75 microm
      i.d., 500 mm) of fused silica containing 50 mM phosphate buffer (pH 2.50) as the
      carrier. UV absorbance detection at 200 nm was performed by an on-column
      detector. The analytes were characterized by their respective migration times.
      Analytical recoveries were 52.6% for PQ and 62.6% for DQ in serum, and 71.4% and
      59.3%, respectively, in urine. The linearity was studied up to 4 mg/L and the
      limits of detection (LODs) were better than 5 pg/mL in serum or urine. The CE
      method described was applied to the characterization of two lethal poisonings and
      results were related.

PMID- 11507717
TI  - Separation of strength and selectivity of mobile phase by spectral mapping
      technique.
AB  - The retention behaviour of seven monotetrazolium and nine ditetrazolium salts was
      studied in seven different mobile phases on alumina and impregnated alumina
      stationary phases. The strength and selectivity of the components of mobile
      phases were separately calculated by the spectral mapping technique. It was
      established that tetrahydrofuran (THF) has the highest solvent strength while the
      differences among ethanol, 1-propanol, 2-propanol and dioxane were relatively
      low. The selectivity of THF was also considerably different from those of other
      solvents. Hydrophobicity and electronic parameters were equally involved in the
      retention strength and selectivity of tetrazolium salts, indicating the mixed
      character of their interaction with the alumina stationary phase.

PMID- 11507718
TI  - Analytical method of chondroitin/dermatan sulfates using high performance liquid
      chromatography/turbo ionspray ionization mass spectrometry: application to
      analyses of the tumor tissue sections on glass slides.
AB  - We established a highly sensitive quantitative analytical method for
      chondroitin/dermatan sulfates by LC/MS method. By this method, the unsaturated
      disaccharides produced after the enzymatic digestion of chondroitin/dermatan
      sulfates can be determined in the amounts as low as 0.5 pmol levels. The use of
      tetrabutylammonium hydroxide as an ion-pair reagent for LC/MS allowed us to
      separate unsaturated 4-sulfated disaccharide and unsaturated 6-sulfated
      disaccharide. Furthermore, the peak areas of unsaturated disaccharides were
      increased almost 10 times by the postcolumn addition of acetonitrile. We applied
      this LC/MS method to the analyses of unsaturated disaccharides from
      chondroitin/dermatan sulfates in the tissues sections on glass slides, which were
      prepared from MethA tumor-bearing mice. This method brought about considerable
      reduction in the time distance from sample collection to preparation of
      analytical results.

PMID- 11507719
TI  - International Genetic Epidemiology Society: commentary on Darkness in El Dorado
      by Patrick Tierney.
AB  - The International Genetic Epidemiology Society (IGES) has examined the charges
      against James V. Neel and his colleagues contained in the recently published book
      by Patrick Tierney entitled Darkness in El Dorado: How Scientists and Journalists
      Devastated the Amazon (W.W. Norton, 2000). The book implicates Neel in causing or
      promoting an epidemic of measles among the Yanomamo Indians of Venezuela in 1968
      leading to "hundreds if not thousands" of deaths by using a "dinosaur" vaccine
      (Edmonston B) as a deliberate "experiment" to test his "eugenic" theories.
      Tierney also attempts to link this research, funded by the Atomic Energy
      Commission (AEC), with a broader tapestry of human radiation experiments. To
      investigate these serious charges, the IGES undertook a thorough examination of
      most source documents referenced in Tierney's book, Neel's field logs, notes,
      first-hand reports, contemporary writings, film sound tracks, etc., and conducted
      interviews with many relevant persons. The IGES finds that these allegations are
      false. Neel was not a eugenicist and was in fact highly critical of both the
      scientific basis of eugenics and its coercive social policies. In this regard,
      Tierney has grossly misrepresented Neel's views on a wide range of social
      implications of modern civilization for the long-term health of the gene pool.
      Far from causing an epidemic of measles, Neel did his utmost to protect the
      Yanomamo from the ravages of the impending epidemic by a vaccination program
      using a vaccine that was widely used at the time and administered in an
      appropriate manner. There was nothing experimental about the vaccination program,
      which in fact severely hindered the primary scientific objectives of the
      expedition. Although the research was funded in large part by the AEC, there was
      no element of radiation research and the work had no connection with the ethical
      abuses that have been reported from AEC-sponsored radiation research, such as
      studies of heavy isotopes. Neel's seminal contributions to a broad range of
      topics in human genetics have been extensively chronicled elsewhere. His research
      on the Yanomamo in particular has provided unique insights into the evolutionary
      biology of our species, the role of sociocultural practices, such as kinship
      relationships and selective pressures in shaping the genetic diversity of
      primitive population isolates, as well as the general picture of health in such
      populations. The IGES decries the damage done to the reputation of one of its
      founders and its first President and the misperception this book may have caused
      about the conduct of research in genetic epidemiology. Ethical issues about
      scientific research in primitive populations deserve serious and wide discussion,
      but the IGES condemns the gross misrepresentation of the facts and demonization
      of the principal characters in this book.

PMID- 11507720
TI  - Multipoint analysis using affected sib pairs: incorporating linkage evidence from
      unlinked regions.
AB  - In this paper, we proposed a multipoint method to assess evidence of linkage to
      one region by incorporating linkage evidence from another region. This approach
      uses affected sib pairs in which the number of alleles shared identical by
      descent (IBD) is the primary statistic. This generalized estimating equation
      (GEE) approach is robust in that no assumption about the mode of inheritance is
      required, other than assuming the two regions being considered are unlinked and
      that there is no more than one susceptibility gene in each region. The method
      proposed here uses data from all available families to simultaneously test the
      hypothesis of statistical interaction between regions and to estimate the
      location of the susceptibility gene in the target region. As an illustration, we
      have applied this GEE method to an asthma sib pair study (Wjst et al. [1999]
      Genomics 58:1-8), which earlier reported evidence of linkage to chromosome 6 but
      showed no evidence for chromosome 20. Our results yield strong evidence to
      chromosome 20 (P value = 0.0001) after incorporating linkage information from
      chromosome 6. Furthermore, it estimates with 95% certainty that the map location
      of the susceptibility gene is flanked by markers D20S186 and D20S101, which are
      approximately 16.3 cM apart.

PMID- 11507721
TI  - Association and aggregation analysis using kin-cohort designs with applications
      to genotype and family history data from the Washington Ashkenazi Study.
AB  - When a rare inherited mutation in a disease gene, such as BRCA1, is found through
      extensive study of high-risk families, it is critical to estimate not only age
      specific penetrance of the disease associated with the mutation, but also the
      residual effect of family history once the mutation is taken into account. The
      kin-cohort design, a cross-sectional survey of a suitable population that
      collects DNA and family history data, provides an efficient alternative to cohort
      or case-control designs for estimating age-specific penetrance in a population
      not selected because of high familial risk. In this report, we develop a method
      for analyzing kin-cohort data that simultaneously estimate the age-specific
      cumulative risk of the disease among the carriers and non-carriers of the
      mutations and the gene-adjusted residual familial aggregation or correlation of
      the disease. We employ a semiparametric modeling approach, where the marginal
      cumulative risks corresponding to the carriers and non-carriers are treated non
      parametrically and the residual familial aggregation is described parametrically
      by a class of bivariate failure time models known as copula models. A simple and
      robust two-stage method is developed for estimation. We apply the method to data
      from the Washington Ashkenazi Study [Struewing et al., 1997, N Engl J Med
      336:1401-1408] to study the residual effect of family history on the risk of
      breast cancer among non-carriers and carriers of specific BRCA1/BRCA2 germline
      mutations. We find that positive history of a single first-degree relative
      significantly increases risk of the non-carriers (RR = 2.0, 95% CI = 1.6-2.6) but
      has little or no effect on the carriers.

PMID- 11507727
TI  - Neurophysiological effects of an extract of Eschscholzia californica Cham.
      (Papaveraceae).
AB  - An aqueous alcohol extract of Eschscholzia californica (Ec) has been evaluated
      for benzodiazepine, neuroleptic, antidepressant, antihistaminic and analgesic
      properties, in order to complete the study of the sedative and anxiolytic effects
      previously demonstrated. The plant extract did not protect mice against the
      convulsant effects of pentylenetetrazol, and did not cause muscle relaxant
      effects but appeared to possess an affinity for the benzodiazepine receptor:
      thus, flumazenil, an antagonist of these receptors, suppressed the sedative and
      anxiolytic effects of the extract. The Ec extract induced peripheral analgesic
      effects in mice but did not possess antidepressant, neuroleptic or antihistaminic
      effects.

PMID- 11507728
TI  - Modulatory influence of Andrographis paniculata on mouse hepatic and extrahepatic
      carcinogen metabolizing enzymes and antioxidant status.
AB  - The effects of two doses (50 and 100 mg/kg body wt/day for 14 days) of an 80%
      hydroalcohol extract of Andrographis paniculata and butylated hydroxyanisole
      (BHA) were examined on drug metabolizing enzymes, antioxidant enzymes,
      glutathione content, lactate dehydrogenase (LDH) and lipid peroxidation in the
      liver of Swiss albino mice (6-8 weeks old). The effect of the extract and BHA
      were also examined on lung, kidney and forestomach for the activities of
      glutathione S-transferase (GST), DT-diaphorase (DTD), superoxide dismutase (SOD)
      and catalase. A significant increase in the levels of acid soluble sulphydryl (
      SH) content, cytochrome P450, cytochrome P450 reductase, cytochrome b5 reductase,
      GST, DTD and SOD were observed at both dose levels of extract treatment while
      catalase, glutathione peroxidase and glutathione reductase (GR) showed
      significant increases only at the higher dose in the liver. Both Andrographis
      treated groups showed a significant decrease in activity of LDH and
      malondialdehyde (MDA) formation. BHA treated mice showed a significant increase
      in the levels of cytochrome b(5), GST, DTD, -SH content, GR and catalase in
      liver; while LDH and MDA levels were reduced significantly compared with their
      control values. In the lung, SOD, catalase and DTD, in the kidney catalase, DTD
      and GST, and in the forestomach SOD and DTD showed a significant increase at both
      dose levels of treatment. In BHA treated mice GST, DTD and catalase were
      significantly induced in the lung and along with these enzymes SOD was also
      induced in the kidney. In the case of the forestomach of BHA treated mice GST,
      DTD and SOD were enhanced significantly. These findings indicate the
      chemopreventive potential of Andrographis paniculata against chemotoxicity
      including carcinogenicity.

PMID- 11507729
TI  - The effect of capsaicin on blood glucose, plasma insulin levels and insulin
      binding in dog models.
AB  - Capsicum frutescens has been used to treat diabetes mellitus by traditional
      healers in Jamaica. This study was designed to identify any hypoglycaemic
      principle(s) and to determine the mechanism of action. Purification experiments
      employing thin layer chromatography (TLC) and high performance liquid
      chromatography (HPLC) led to the extraction of the active principle, capsaicin.
      Capsaicin caused a decrease in blood glucose levels of 4.91 +/- 0.52 (n = 6)
      mmol/dL versus 6.40 +/- 0.13 mmol/dL (n = 6) for the control (p < 0.05) at the
      2.5 h time interval when the oral glucose tolerance test (OGTT) was performed on
      dogs treated with capsaicin and compared with the control. Plasma insulin levels
      measured at the 2.5 h time interval showed that there was an increase in plasma
      insulin levels of 5.78 +/- 0.76 microIU/mL (n = 6) for the capsaicin treated dogs
      versus 3.70 +/- 0.43 microIU/mL (n = 10) for the control (p < 0.05). Insulin
      receptor studies, using a modification of the method of Gambhir et al. done on
      monocytes obtained from blood at the 2.5 h time interval showed that there was a
      decrease in the percentage receptor binding for the capsaicin treated dogs when
      compared with the control. Insulin affinity results showed that there was a
      decrease of 2.4 x 10(-4) in monocytes for the capsaicin treated dogs versus 8.77
      x 10(-4) for the control (p < 0.05). Also, insulin receptor calculations showed a
      decrease in number, 2.63 x 10(8) +/- 5.73 x 10(7), compared with 8.77 x 10(8) +/-
      1.47 x 10(8) for the control. In conclusion it can be stated that capsaicin is
      responsible for the hypoglycaemic episodes seen in the dogs and that it also
      causes an increase in insulin secretion which leads to a reduction of insulin
      binding on the insulin receptors.

PMID- 11507730
TI  - Impact of certain flavonoids on lipid profiles--potential action of Garcinia
      cambogia flavonoids.
AB  - Flavonoids from Cocos nucifera, Myristica fragrance, Saraka asoka and Garcinia
      cambogia exerted hypolipidaemic activity in rats. Lipid lowering activity was
      maximum in rats administered flavonoids (10 mg/kg BW/day) from Garcinia cambogia.
      A dose response study revealed biphasic activity. Higher doses were less
      effective in reducing lipid levels in serum and tissues, although devoid of toxic
      effects.

PMID- 11507731
TI  - Screening of Malian medicinal plants for antifungal, larvicidal, molluscicidal,
      antioxidant and radical scavenging activities.
AB  - A total of 78 different extracts from 20 medicinal plants belonging to 14 plant
      families from Mali were tested for their antifungal, larvicidal, molluscicidal,
      antioxidant and radical scavenging activities. Dichloromethane, methanol, water
      and ethanol extracts were used. TLC autobiography for antifungal activity was run
      with Cladosporium cucumerinum and Candida albicans. Extracts were also tested on
      the larvae of the mosquitoes Aedes aegypti, Anopheles gambiae and Culex
      quinquefasciatus. Molluscicidal activities were established with the snails
      Biomphalaria glabrata, Biomphalaria pfeifferi and Bulinus truncatus. beta
      Carotene and DPPH solutions sprayed on TLC plates were used for antioxidant and
      radical scavenging assays. Of the extracts investigated, 20% were antioxidant and
      radical scavengers, 19% fungicidal, 30% were larvicidal and 11% were
      molluscicidal. Three of the plant extracts, from Cussonia barteri (Araliaceae),
      Glinus oppositifolius (Aizoaceae) and Lannea velutina (Anacardiaceae) gave
      positive responses in all four tests.

PMID- 11507732
TI  - The antiulcerative effect of Thai Musa species in rats.
AB  - Bananas are reported to have an antipeptic ulcer effect, however, the beneficial
      action can be affected by many factors, including the variety. Our study was
      undertaken to investigate the antipeptic ulcer effect of the Palo and Horn
      varieties of banana, grown and consumed in the northeast of Thailand.
      Indomethacin and acetic acid-induced gastric lesions in rats were employed as
      models of peptic ulcer disease. The lengths of gastric lesions in the glandular
      part of the stomach were measured for the assessment of the protective effect of
      bananas. The healing effect was studied by histological examination of the
      ulcerated area. The lesions in rats treated with the extract of banana were
      significantly less dominant than those of the control. The average length of
      total lesions of rats treated with an extract of Palo or Horn bananas at a dose
      of 1.0 g/kg/d for 3 days prior to indomethacin administration were 4.47+/-1.2 and
      1.87+/-0.44 mm, respectively, whereas those observed in the control rats were
      14.56+/-2.43 mm. In the ulcer-healing model, only the Hom-banana-extract-treated
      group showed a beneficial effect which manifested as a milder degree of
      histological change than that of the indomethacin-induced-chronic-ulcer control
      group. However, in acetic acid-induced ulcers, the histological changes of every
      group were similar. The present findings indicate that bananas of different
      varieties have varying antipeptic ulcer effects. The extracts of Palo and Hom
      bananas have a prominent gastroprotective effect, whereas only the extract of Hom
      banana had an observed ulcer-healing effect.

PMID- 11507733
TI  - A study of prostane in the treatment of benign prostatic hyperplasia.
AB  - A clinical trial was conducted in a study group of 70 males diagnosed with
      symptomatic benign prostatic hypertrophy (BPH) (synonym of benign prostatic
      hyperplasia). They were administered Prostane, a herbal formulation, at a dose of
      two tablets a day for 1 year and monitored every 4 months during the study
      period. Analysis of the results showed an improvement in the symptom score of the
      American Urological Association symptom index rating. There was total relief in
      pain and haematuria in all the patients (100%); dribbling of urine decreased in
      67%, dysuria in 50%, urgency in 60% and hesitancy in 40%. Blood urea levels were
      within the normal range in 70% of the patients and in the range 31-40 mg/dL in
      the remaining patients of the study group. Serum prostate specific antigen levels
      returned to normal in 56% of patients and were in the range 4.1-5.0 ng/mL in 25%
      of patients. There was a decrease in prostate specific antigen values which were
      >6 ng/mL in 9 patients at the commencement of the trial. Uroflowmetry studies
      showed that the peak flow increased from 12.6 to 30.7 s (p<0.001) and the void
      volume from 60.72 to 660 mL (p<0.001), the latent period reduced from 12.78 s to
      2.61 s; the flow time from 57.01 s to 20.17 s and the residual volume from 620 mL
      to 20 mL (p<0.001). From these results, it is evident that Prostane was effective
      in alleviating symptoms, reducing prostate specific antigen values and
      normalizing uroflow dynamics in patients with benign prostatic hypertrophy.

PMID- 11507734
TI  - The relaxation of isolated rabbit corpus cavernosum by the herbal medicine
      Catuama and its constituents.
AB  - The effects of the Brazilian herbal medicine Catuama and each of its plant
      constituents (Paullinia cupana, Trichilia catigua, Zingiber officinalis and
      Ptychopetalum olacoides) were investigated on rabbit corpus cavernosum (RbCC)
      using a bioassay cascade. Catuama caused short-lived and dose-dependent
      relaxations (11% +/- 7%, 26% +/- 5% and 82% +/- 9%, at doses of 1, 3 and 10 mg,
      respectively). Neither the nitric oxide synthesis inhibitor N(omega)-nitro-L
      arginine methyl ester (L-NAME; 10 microM) nor the soluble guanylate cyclase
      inhibitor ODQ (10 microM) significantly affected the Catuama-induced relaxations.
      Similarly, the selective ATP-dependent K(+) channel (K(ATP)) blocker
      glibenclamide (10 microM), the muscarinic receptor antagonist atropine (1 microM)
      and the voltage-dependent Na(+) channel blocker tetrodotoxin (1 microM) all
      failed to affect significantly the Catuama-induced relaxations. These results
      indicate that the relaxations induced by Catuama involve neither nitric oxide
      release nor K(ATP) channel activation. The extracts of P. cupana, Z. officinalis
      and P. olacoides caused short-lived and dose-dependent RbCC relaxations, whereas
      T. catigua evoked long-lasting relaxations which were occasionally preceded by a
      brief contractile effect. The extract of P. cupana was the most active in
      relaxing RbCC strips. The relaxations induced by all extracts were not
      significantly affected by L-NAME (10 microM). The infusion of ODQ (10 microM) had
      no significant effect on the P. cupana- and Z. officinalis-induced relaxations
      but reduced by >50% (p < 0.05) those evoked by P. olacoides and T. catigua.
      Incubations of RbCC with Catuama(10 mg/mL for 0.25 to 5 min) caused increases of
      cAMP levels (143% increase at 5 min of incubation). Incubations of RbCC with P.
      cupana extract (1 mg/mL) increased the cAMP levels by 200% whereas higher doses
      (10 and 100 mg/mL) caused smaller increases in the nucleotide levels (150% and
      89%, respectively). The extracts of Z. officinalis and P. olacoides (same doses)
      caused smaller increases of the cAMP levels compared with the P. cupana extract,
      whereas T. catigua (1-100 mg) did not increase the levels of this nucleotide
      above the basal values. Our results show that of the four extracts assayed, P.
      cupana was the most effective, indicating that it is the main extract responsible
      for the relaxing effect of Catuama on rabbit cavernosal tissue.

PMID- 11507735
TI  - Effects of linalool on [(3)H]MK801 and [(3)H] muscimol binding in mouse cortical
      membranes.
AB  - Linalool is a monoterpene compound reported to be a major component of essential
      oils of several aromatic species. Several linalool-producing species are used in
      traditional medical systems for sedative purposes, including the interruption and
      prevention of seizures. Previous studies in mice revealed that linalool modulates
      glutamatergic (competitive antagonism of L-[(3)H]glutamate binding, delayed
      intraperitoneal NMDA-induced convulsions and blockade of intracerebroventricular
      Quin-induced convulsions) and GABAergic transmission (protection against
      pentylenetetrazol and picrotoxin-induced convulsions). To further clarify the
      anticonvulsive mechanisms of linalool, we studied the effects of linalool on
      binding of [(3)H]MK801 (NMDA antagonist) and [(3)H]muscimol (GABA(A) agonist) to
      mouse cortical membranes. Linalool showed a dose dependent non-competitive
      inhibition of [(3)H]MK801 binding (IC(50) = 2.97 mM) but no effect on
      [(3)H]muscimol binding. The data suggest that the anticonvulsant mode of action
      of linalool includes a direct interaction with the NMDA receptor complex. The
      data do not, however, support a direct interaction of linalool with GABA(A)
      receptors, although changes in GABA-mediated neuronal inhibition or effects on
      GABA release and uptake cannot be ruled out.

PMID- 11507737
TI  - Antidiarrhoeal activity of the aqueous extract of Terminalia avicennoides roots.
AB  - The antidiarrhoeal effects of the aqueous root extract of Terminalia avicennoides
      were evaluated in rodents. Studies were carried out on the isolated rabbit
      jejunum, gastrointestinal motility in vivo and on castor oil-induced diarrhoea in
      mice. The results revealed that the extract exhibited a concentration-dependent
      inhibition of the spontaneous pendular movement of the isolated rabbit jejunum
      and attenuated acetylcholine induced contractions. The extract (100, 200 and 400
      mg/kg) also caused a dose-dependent decrease of gastrointestinal transit and
      markedly protected mice against castor oil-induced diarrhoea. The intraperitoneal
      LD(50) of the extract was found to be 871.4-917.4 mg/kg in mice (95% confidence).
      A preliminary phytochemical screening of the aqueous extract of T. avicennoides
      roots revealed the presence of tannins, saponins and flavonoids. The results
      obtained showed that the water extract of T. avicennoides roots may contain some
      biologically active principles that may be active against diarrhoea and this may
      be the basis for its use traditionally for gastrointestinal disorders.

PMID- 11507736
TI  - Anticonvulsant activities of the FS-1 subfraction isolated from roots of
      Delphinium denudatum.
AB  - Delphinium denudatum Wall. (Ranunculaceae) is a medicinal herb used for the
      treatment of epilepsy in the subcontinent. The present study reports the
      anticonvulsant activities in the maximal electroshock test (MEST) and
      subcutaneous pentylenetetrazole (PTZ), bicuculline (BIC), picrotoxin (PIC)
      induced seizures of the FS-1 subfraction (FS-1) that was obtained by purification
      of an aqueous fraction isolated from the roots of D. denudatum. In CF 1 mice, FS
      1 (600 mg/kg i.p.) exhibited very potent anticonvulsant activity that was
      comparable to the effects of the well-known antiepileptic drug phenytoin (20
      mg/kg) in MEST and protected 100% animals from hind limb tonic extension phase of
      this model. FS-1 also suppressed PTZ-induced threshold seizure and the loss of
      the righting reflex with tonic fore and hind limb extension by 100%, similar to
      the antiepileptic drug valproic acid (350 mg/kg). BIC-induced seizures were
      suppressed in 80% of the animals. FS-1 exhibited weak anticonvulsant effect on
      PIC-induced seizures, however, it significantly reduced mortality and delayed the
      onset of seizures. FS-1 had no effect on strychnine (STN)-induced extensor
      seizures. The results demonstrate the broad and potent anticonvulsant activity of
      the compounds in FS-1 of D. denudatum.

PMID- 11507738
TI  - Evaluation of the potency activity of aphrodisiac in Eurycoma longifolia Jack.
AB  - The butanol, methanol, water and chloroform extracts of the roots of Eurycoma
      longifolia Jack were studied using various tests of potency of treated male rats.
      The results showed that E. longifolia produced a dose-dependent, recurrent and
      significant increase in the episodes of penile reflexes as evidenced by increases
      in quick flips, long flips and erections of the treated male rats during the 30
      min observation period. These results provide further evidence that E. longifolia
      increases the aphrodisiac potency activity in treated animals.

PMID- 11507739
TI  - Antimicrobial activity of seed extracts and bondenolide from Caesalpinia bonduc
      (L.) Roxb.
AB  - The antibacterial and antifungal activities, along with a phytotoxicity test of
      the newly isolated diterpene bondenolide (1), of a methanol extract, ethylacetate
      fraction and water soluble part of the methanol extract of Caesalpinia bonduc
      (L.) Roxb. were assayed.

PMID- 11507740
TI  - Cytotoxic coumarins and lignans from extracts of the northern prickly ash
      (Zanthoxylum americanum).
AB  - Four pyranocoumarins; dipetaline, alloxanthoxyletin, xanthoxyletin and
      xanthyletin; and two lignans; sesamin and asarinin were isolated from the
      northern prickly ash, Zanthoxylum americanum. To varying degrees, all inhibited
      the incorporation of tritiated thymidine into human leukaemia (HL-60) cells.
      Dipetaline was the most active with an IC(50) of 0.68 ppm, followed by
      alloxanthoxyletin (1.31 ppm), sesamin (2.71 ppm), asarinin (4.12 ppm),
      xanthoxyletin (3.48 ppm) and xanthylletin (3.84 ppm).

PMID- 11507741
TI  - Effect of quercetin on tachykinin-induced plasma extravasation in rat urinary
      bladder.
AB  - The effect of quercetin on substance P-induced plasma extravasation in rat
      urinary bladder and its modulation by endogenous peptidases in conscious rats was
      studied. Plasma protein extravasation (PE) was assayed by measurement of
      extravasated Evans blue dye (microg/g dry tissue). Intravenous injection of
      substance P (SP, 10 nmol/kg) significantly increased PE in the urinary bladder.
      PE evoked by SP was increased significantly by quercetin (20 mg/kg, p.o.)
      pretreatment in the urinary bladder (73.5 +/- 4.9 to 152.2 +/- 9.9). Pretreatment
      with captopril, an angiotensin-converting enzyme (ACE) inhibitor (10 nmol/kg,
      i.v.), or with phosphoramidon, a neutral endopeptidase (NEP) inhibitor (2.5
      micromol/kg, i.v.) also potentiated the SP-induced PE in urinary bladder, 286.2
      +/- 20.4 and 323.3 +/- 34.0, respectively. Quercetin did not show any effect on
      neurokinin-A (NKA, 10 nmol/kg, i.v.) -induced plasma extravasation. The present
      study demonstrates that quercetin potentiates the PE induced by substance P in
      the urinary bladder. These effects suggest that this flavonoid might cause
      inhibition of NEP and/or ACE.

PMID- 11507742
TI  - Cardiovascular effects of the methanol and dichloromethanol extracts from Mentha
      suaveolens Ehrh.
AB  - Methanol and dichloromethanol extracts of the leaves and stems of Mentha
      suaveolens Ehrh. have been tested for their effects on resting arterial blood
      pressure, heart rate and noradrenaline induced hypertension. Both extracts
      administered by i.v. bolus to urethane anaesthetized normotensive rats reduced
      the mean arterial blood pressure and heart rate, while only the dichloromethanol
      extract prevented the noradrenaline induced hypertension.

PMID- 11507743
TI  - The antioxidant activity of standardized extract of Ginkgo biloba (EGb 761) in
      rats.
AB  - The standardized extract of Ginkgo biloba (EGb 761) has been widely employed for
      its significant benefit in neurodegenerative disorders. Although antioxidative
      actions have been attributed to this extract, the mechanisms of the multiple
      principles involved in this pharmacological activity are not completely
      established. Parkinson's and Alzheimer's diseases are frequently associated with
      oxidative stress and defects in the cellular protective mechanisms. In this
      study, the lipid peroxidation (LPO) and the activity of the antioxidant enzymes,
      catalase (CAT) and superoxide dismutase (SOD) were evaluated in the hippocampus,
      striatum and substantia nigra (SN) of rats treated with EGb 761. An increase in
      the CAT and SOD activities in the hippocampus, striatum and SN, and a decrease of
      the LPO in the hippocampus were observed. These data are additional to the
      antioxidant properties of EGb 761 reported in the literature and indicate a
      possible role for the extract in the treatment of diseases involving free
      radicals and oxidative damage.

PMID- 11507744
TI  - Antihypertensive effect of an aqueous extract of Zygophyllum coccineum L. in
      rats.
AB  - The effects of an aqueous extract of Zygophyllum coccineum L. on rat blood
      pressure (BP) and on the mesenteric vascular bed were investigated. The extract
      dose-dependently reduced BP and heart rate in normotensive and spontaneously
      hypertensive rats (SHRs). It also reduced BP in pithed SHRs. In vitro, the
      extract had no effect on basal perfusion pressure of the mesenteric vascular bed.
      When the perfusion pressure was raised with noradrenaline or potassium chloride,
      the extract produced a dose-dependent reduction in perfusion pressure. However,
      in preparations in which the perfusion pressure was raised with KCl, the
      depressor response to lower doses of the extract was abolished while higher doses
      produced responses that were reduced in magnitude when compared with similar
      responses in preparations in which the perfusion pressure was raised with
      noradrenaline. It was concluded that extracts of Z. coccineum possess significant
      antihypertensive activity that may involve some membrane hyperpolarization.

PMID- 11507745
TI  - Evaluation of the antidiabetic action of Mangifera indica in mice.
AB  - The leaves of Mangifera indica were assessed for antidiabetic properties using
      normoglycaemic, glucose-induced hyperglycaemia and streptozotocin (STZ) induced
      diabetic mice. The aqueous extract produced a reduction of blood glucose level in
      normoglycaemic and glucose-induced hyperglycaemia, but did not have any effect on
      streptozotocin-induced diabetic mice. The hypoglycaemic effect of the aqueous
      extract was compared with that of an oral dose of chlorpropamide under the same
      conditions. The results of this study indicate that the aqueous extract of the
      leaves of Mangifera indica possess hypoglycaemic activity.

PMID- 11507748
TI  - Selected bibliography.

PMID- 11507746
TI  - Metabolism of 1,8-dihydroxy 3-hydroxy methyl anthraquinone (aloe-emodin) isolated
      from the leaves of Cassia tora in albino rats.
AB  - Cassia tora is a well known plant of India. Aloe-emodin was isolated from the
      leaves of this plant and its metabolism pattern was studied. The results showed
      that about 15.4% of the administered aloe-emodin was excreted and the rest was
      probably bound or metabolized in the system.

PMID- 11507749
TI  - A comprehensive on-line digestion-liquid chromatography/mass
      spectrometry/collision-induced dissociation mass spectrometry approach for the
      characterization of human fibrinogen.
AB  - An automatic on-line digestion-liquid chromatography/mass spectrometry/collision
      induced dissociation mass spectrometry (LC-MS/CID-MS) protocol has been developed
      for detection of errors in the biosynthesis of human fibrinogen, such as amino
      acid (AA) mismatch or incorrect post-translational modification (PTM). Using on
      line digestion on an immobilized-enzyme column, the reaction time is
      significantly reduced (less than 20 min) and the entire approach is suitable for
      automation. The two-loop MS experiments (full-scan acquisition and sugar moieties
      monitoring by SIM) allow checking both the correct AA mapping via the peptides
      generated by the digestion of the PTM. Since the protocol was designed for
      application on a routine basis, as a proof-of-concept detection of a rare case of
      'abnormal' fibrinogen has been demonstrated. The advantage of the proposed
      approach is exemplified by the fact that the DNA sequence information for the
      case investigated had not shown any evidence of the abnormality.

PMID- 11507750
TI  - Method development for measuring trace levels of penicillins in aqueous
      environmental samples.
AB  - A method based on liquid chromatography/mass spectrometry with an electrospray
      ion source and a single quadrupole instrument (LC/ES-MS) has been developed for
      determining trace levels of eight widely used penicillins in aqueous
      environmental samples. Analyte extraction was performed from 4 L tap water, 2 L
      groundwater, 1 L river water, 0.2 L treated sewage and 0.1 L raw sewage, by using
      a Carbograph 4 cartridge. During removal of the solvent, penicillins were
      purposely allowed to convert into their penicilloyl methyl esters. This 'in situ'
      derivatization step resulted in a dramatic enhancement of the response of the ES
      MS system for non-amphoteric penicillins. Analyte recoveries were better than 80%
      irrespective of the type of aqueous sample, with the exception of amoxicillin
      (76%) and ampicillin (77%) in tap water. At the level of 50 ng/L of each analyte
      in ground water, the within-day precision was in the range 6-10%. Calibration
      curves were linear for injected amounts up to 800 ng, with R(2) in the range
      0.9952-0.9995. When injecting large equivalent volumes of the aqueous samples,
      the electrospray matrix effect altered in-source collision-induced dissociation
      (CID) spectra of the analytes by severely weakening signals for fragment ions, as
      compared to spectra of reference standards. Remedies to obviate this anomalous
      unwelcome effect are suggested. On the basis of a signal-to-noise ratio of 10,
      limits of quantification were estimated to range between 2 (cloxacillin) and 24
      ng/L (amoxicillin) in river water.

PMID- 11507751
TI  - Direct determination of phosphorylated intracellular anabolites of stavudine
      (d4T) by liquid chromatography/tandem mass spectrometry.
AB  - The objective was to develop and validate a routine assay for active
      intracellular anabolites of stavudine (d4T), a nucleoside reverse transcriptase
      inhibitor in human PBMC, applicable to pharmacokinetic studies and treatment
      monitoring. This was achieved using liquid chromatography coupled to tandem mass
      spectrometry (LC/MS/MS), which theoretically allies optimum sensitivity,
      specificity and high sample throughput. After cellular lysis in a Tris/methanol
      buffer, the extract spiked with 2[H(8)]-ATP (internal standard) is directly
      injected into the LC/MS/MS system. Phosphorylated metabolites of d4T as well as
      deoxythymidine-triphosphate, the competitor on the reverse transcriptase, are
      separated from d4T on a reverse-phase microbore column with ion pairing. The
      detection is performed in the multiple reaction monitoring (MRM) mode after drug
      ionisation in negative mode electrospray. The limit of quantitation for d4T-TP
      was 138 fmol per 7 mL blood (9.8 fmol per 10(6) cells) and CV% for repeatability
      and intermediate precision were lower than 15%. Stability of compounds was
      checked before and during the process of isolation of PBMC. Cellular samples from
      several d4T-treated patients were successfully analysed using this method and d4T
      triphosphate and deoxythymidine triphosphate were recovered. In conclusion, we
      have developed and validated a routine LC/MS/MS method that allows the
      simultaneous determination of mono-, di- and triphosphorylated anabolites of d4T
      in PBMC as well as the natural corresponding triphosphate in one analysis. For
      the first time, the chain terminator ratio (d4T-TP/dT-TP) could be directly
      measured. This method can be used simply and routinely on more than 35 samples
      per day. Extension to other nucleoside analogues is under development.

PMID- 11507752
TI  - Ammonia chemical ionization tandem mass spectrometry in structural determination
      of alkaloids. II. Tetraponerines from pseudomyrmecine ants.
AB  - Chemical ionization tandem mass spectrometry (CI-MS/MS) of alkaloids with ammonia
      reagent gas and collision-activated dissociation as well as EI-MS/MS were applied
      to the tetraponerine alkaloids in extracts from six pseudomyrmecine ants of the
      genus Tetraponera. The MS/MS techniques along with gas chromatography Fourier
      transform infrared (GC/FTIR) spectra allowed identification in two extracts of
      seven of the eight known tetraponerines. The EI-MS/MS fragmentations proved
      diagnostic for the ring system and the CI-MS/MS patterns for the C-8 or C-9
      substitution, while the Bohlmann bands in FTIR spectra were diagnostic for the C
      8 or C-9 configurations. An Indian ant (T. allaborans) had T-2, T-4 and T-8,
      while a Chinese ant (T. binghami) had T-5, T-6, T-7 and T-8. Four other ants, T.
      rufonigra (India), T. penzigi (Africa), T. clypeata (Africa) and T. sp. cf.
      emeryi (Africa), had no tetraponerines.

PMID- 11507753
TI  - Improvement of in-gel digestion protocol for peptide mass fingerprinting by
      matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.
AB  - High-sensitivity, high-throughput analysis of proteins for proteomics studies is
      usually performed by polyacrylamide gel electrophoresis in combination with mass
      spectrometry. However, the quality of the data obtained depends on the in-gel
      digestion procedure employed. This work describes an improvement in the in-gel
      digestion efficiency for matrix-assisted laser desorption/ionization time-of
      flight mass spectrometry (MALDI-TOFMS) analysis. A dramatic improvement in the
      coverage of tryptic peptides was observed when n-octyl glucoside was added to the
      buffer. Whole cell extracted proteins from S. cerevisiae were separated by two
      dimensional gel electrophoresis and stained with silver. Protein spots were
      identified using our improved in-gel digestion method and MALDI-TOFMS. In
      addition, the mass spectra obtained by using the matrix alpha-cyano-4
      hydroxycinnamic acid (CHCA) were compared with those obtained using 2,5
      dihydroxybenzoic acid (DHB). The DHB matrix usually gave more peaks, which led to
      higher sequence coverage and, consequently, to higher confidence in protein
      identification. This improved in-gel digestion protocol is simple and useful for
      protein identification by MALDI-TOFMS.

PMID- 11507754
TI  - Two-photon ionization thresholds of matrix-assisted laser desorption/ionization
      matrix clusters.
AB  - Direct two-photon ionization of the matrix has been considered a likely primary
      ionization mechanism in matrix-assisted laser desorption/ionization (MALDI) mass
      spectrometry. This mechanism requires that the vertical ionization threshold of
      matrix materials be below twice the laser photon energy. Because dimers and
      larger aggregates may be numerous in the early stages of the MALDI plume
      expansion, their ionization thresholds are important as well. We have used two
      color two-photon ionization to determine the ionization thresholds of jet cooled
      clusters of an important matrix, 2,5-dihydroxy benzoic acid (DHB), and mixed
      clusters with the thermal decomposition product of DHB, hydroquinone. The
      thresholds of the clusters were reduced by only a few tenths of an eV compared to
      the monomers, to an apparent limit of 7.82 eV for pure DHB clusters. None of the
      investigated clusters can be directly ionized by two nitrogen laser photons (7.36
      eV), and the ionization efficiency at the thresholds is low.

PMID- 11507755
TI  - Application of DNA-binding polymers for preparation of DNA for analysis by matrix
      assisted laser desorption/ionization mass spectrometry.
AB  - The susceptibility of matrix-assisted laser desorption/ionization mass
      spectrometry (MALDI-MS) to the presence of salts in a sample, especially salts of
      alkali metals, requires careful and often tedious desalting procedures which
      complicate and slow the throughput of MS-based methods. A novel approach to
      sample preparation was developed based on the extraction of DNA out of solution
      onto a solid surface with an attached DNA-binding polymer, such as
      polyethyleneimine or polyvinylpyrrolidone. The observed binding is strong enough
      to sustain washing, and, as a result, desalting and concentration can be
      performed in a single fast step. After DNA has been immobilized on the surface
      and supernatant solution removed, subsequent addition of MALDI matrix releases
      material from the surface, which co-crystallizes with matrix. The mass
      spectrometric analysis is then performed directly from this support. Analysis of
      oligonucleotides and three-fold multiplexed SNP typing reactions performed by
      this method shows improved sensitivity and excellent resolution for various DNA
      fragments, together with high tolerance to various buffer components, such as
      alkali metals and surfactants. Simplicity and speed make it attractive for high
      throughput sample preparation and analysis of oligonucleotide mixtures by MALDI
      MS.

PMID- 11507756
TI  - Strategies for determination of insulin with tandem electrospray mass
      spectrometry: implications for other analyte proteins?
AB  - Using human insulin (MW 5808 Da) as a model compound, the possible strategies
      towards optimization of sensitivity and selectivity of measurement by
      electrospray ionization with a standard triple quadrupole mass spectrometer were
      investigated. For measurement in selected ion-monitoring (SIM) mode, these
      strategies involved systematic variation of instrumental parameters and spray pH.
      In this investigation four different operating modes were used corresponding to
      positive/negative ionization modes with acidic/basic sprays and pH reversed
      (hereafter termed 'wrong-way-round' operation); the cone voltage was optimized
      for each mode of operation. When collision-activated dissociation (CAD) is
      employed, two additional operation modes are possible: namely, low collision
      energies (10-35 eV, CAD-l) for the generation of sequence-specific fragments and
      high collision energies (>80 eV, CAD-h) for the generation of nonspecific
      fragments. Overall, this results in twelve different modes of operation. Loop
      injection of aqueous insulin standards were run for each of the twelve operating
      modes and measurements made for five different charge states (n = 2-6) observable
      with our instrument that has an upper mass limit of m/z 4000. The signal/noise
      (S/N) ratio was optimized for each charge state, resulting in 60 measurements.
      The best S/N ratios (20 000) were achieved under positive SIM conditions with
      charge state 6 (m/z 969) and under 'wrong-way-round' negative SIM conditions with
      charge state 3 (m/z 1935). Lower S/N ratios were observed under positive CAD-h
      conditions with charge state 5 (m/z 1163, S/N 15 000) and positive CAD-l
      conditions with charge state 6 (m/z 969, S/N 10 000). All other operating modes
      gave maximum S/N ratios of 4000. For measurement of insulin standards, the
      results obtained show SIM to give the best S/N ratio. However, for samples in
      complex matrices, our general experience suggests CAD to be the preferable
      operating mode. Consequently, for the development of a quantitative method for
      proteins in general, it might be advocated that all of the twelve operating modes
      and all relevant charge states be investigated to find the optimum S/N ratio.

PMID- 11507757
TI  - Consequence of boar edible tissue consumption on urinary profiles of nandrolone
      metabolites. II. Identification and quantification of 19-norsteroids responsible
      for 19-norandrosterone and 19-noretiocholanolone excretion in human urine.
AB  - In previous work (Le Bizec et al., Rapid Commun. Mass Spectrom. 2000; 14: 1058),
      it was demonstrated that a boar meal intake could lead to possible false
      accusations of abuse of 17beta-nortestosterone in antidoping control. The aim of
      the present study was to identify and quantify endogenous 19-norsteroids in boar
      edible tissue at concentrations that can alter the steroid urinary profile in
      humans, and lead to excretion of 19-norandrosterone (19-NA) and 19
      noretiocholanolone (19-NE). The samples were analysed in two laboratories. The
      methodologies used for extraction and detection (GC/MS(EI) and LC/MS/MS(APCI+))
      are compared and discussed. 19-Norandrostenedione (NAED), 17beta- and 17alpha
      nortestosterone (bNT, aNT), and 17beta- and 17alpha-testosterone (bT, aT) were
      quantified. The largest concentrations of NAED and bNT were observed in testicles
      (83 and 172 microg/kg), liver (17 and 63 microg/kg) and kidney (45 and 38
      microg/kg). A correlation between the bNT and NAED content of a typical meal
      prepared with boar parts and the excreted concentrations of 19-NA and 19-NE in
      human urine was demonstrated.

PMID- 11507758
TI  - Infrared matrix-assisted laser desorption/ionization of polycyclic aromatic
      hydrocarbons with a sulfolane matrix.
AB  - Infrared matrix-assisted laser desorption/ionization (IR-MALDI) of the
      polyaromatic hydrocarbons (PAHs) anthracene, benzo[a]pyrene, and
      dibenz[a,h]anthracene was performed using a 10.6-microm CO2 laser and a liquid
      matrix. Sulfolane (tetrahydrothiophene 1,1-dioxide) was found to be an effective
      matrix for PAH ionization: mass spectra obtained with a sulfolane matrix contain
      an intense molecular ion peak; interference from PAH fragment and matrix peaks is
      negligible in all cases. The main limitation of the sulfolane matrix is sample
      evaporation after 3 to 5 min in vacuum. This sample lifetime can be increased to
      between 15 and 30 min using a 2:1 (v/v) mixture of sulfolane and glycerol, but
      the resulting spectra have greater matrix interference and decreased shot-to-shot
      signal stability.

PMID- 11507759
TI  - Gas-phase conformers of the [M + 2H](2+) ion of bradykinin investigated by
      combining high-field asymmetric waveform ion mobility spectrometry,
      hydrogen/deuterium exchange, and energy-loss measurements.
AB  - The continuous separation capability of high-field asymmetric waveform ion
      mobility spectrometry (FAIMS) was used in combination with complementary
      techniques for probing biomolecular ions in the gas phase. Gas-phase conformers
      of the [M + 2H](2+) ion of bradykinin were examined using a combination of FAIMS,
      H/D exchange, and energy-loss measurements. When FAIMS data and H/D exchange data
      were analyzed separately, the presence of only two conformers of the [M + 2H](2+)
      ion of bradykinin could be detected. However, in an experiment in which FAIMS and
      H/D exchange were combined, at least four different conformers of the gas-phase
      [M + 2H](2+) ion of bradykinin were detected, including one of very low
      abundance. Cross sections calculated for the four conformers, based on energy
      loss measurements, were 250, 240, 250, and 244 A(2), in order of decreasing
      abundance.

PMID- 11507760
TI  - Proton mobility and main fragmentation pathways of protonated lysylglycine.
AB  - Theoretical model calculations were performed to validate the 'mobile proton'
      model for protonated lysylglycine (KG). Detailed scans carried out at various
      quantum chemical levels of the potential energy surface (PES) of protonated KG
      resulted in a large number of minima belonging to various protonation sites and
      conformers. Transition structures corresponding to proton transfer reactions
      between different protonation sites were determined, to obtain some energetic and
      structural insight into the atomic details of these processes. The rate
      coefficients of the proton transfer reactions between the isomers were calculated
      using the Rice-Ramsperger-Kassel-Marcus (RRKM) method in order to obtain a
      quantitative measure of the time-scale of these processes. Our results clearly
      indicate that the added proton is less mobile for protonated KG than for peptides
      lacking a basic amino acid residue. However, the energy needed to reach the
      energetically less favorable but-from the point of view of backbone fragmentation
      critical amide nitrogen protonation sites is available in tandem mass
      spectrometers operated under low-energy collision conditions. Using the results
      of our scan of the PES of protonated KG, the dissociation pathways corresponding
      to the main fragmentation channels for protonated KG were also determined. Such
      pathways include loss of ammonia and formation of a protonated alpha-amino
      epsilon-caprolactam. The results of our theoretical modeling, which revealed all
      the atomic details of these processes, are in agreement with the available
      experimental results.

PMID- 11507761
TI  - Analysis of synthetic chemical drugs in adulterated Chinese medicines by
      capillary electrophoresis/electrospray ionization mass spectrometry.
AB  - Sixteen synthetic chemical drugs, often found in adulterated Chinese medicines,
      were studied by capillary electrophoresis/UV absorbance (CE/UV) and capillary
      electrophoresis/electrospray ionization mass spectrometry (CE/ESI-MS). Only nine
      peaks were detected with CZE/UV, but on-line CZE/MS provided clear identification
      for most compounds. For a real sample of a Chinese medicinal preparation, a few
      adulterants were identified by their migration times and protonated molecular
      ions. For coeluting compounds, more reliable identification was achieved by MS/MS
      in selected reaction monitoring mode. Micellar electrokinetic chromatography
      (MEKC) using sodium dodecyl sulfate (SDS) provided better separation than
      capillary zone electrophoresis (CZE), and, under optimal conditions, fourteen
      peaks were detected using UV detection. In ESI, the interference of SDS was less
      severe in positive ion mode than in negative ion mode. Up to 20 mM SDS could be
      used in direct coupling of MEKC with ESI-MS if the mass spectrometer was operated
      in positive ion mode. Because of better resolution in MEKC, adulterants can be
      identified without the use of MS/MS.

PMID- 11507762
TI  - Selective analysis of phosphopeptides within a protein mixture by chemical
      modification, reversible biotinylation and mass spectrometry.
AB  - A new method combining chemical modification and affinity purification is
      described for the characterization of serine and threonine phosphopeptides in
      proteins. The method is based on the conversion of phosphoserine and
      phosphothreonine residues to S-(2-mercaptoethyl)cysteinyl or beta-methyl-S-(2
      mercaptoethyl)cysteinyl residues by beta-elimination/1,2-ethanedithiol addition,
      followed by reversible biotinylation of the modified proteins. After trypsin
      digestion, the biotinylated peptides were affinity-isolated and enriched, and
      subsequently subjected to structural characterization by liquid
      chromatography/tandem mass spectrometry (LC/MS/MS). Database searching allowed
      for automated identification of modified residues that were originally
      phosphorylated. The applicability of the method is demonstrated by the
      identification of all known phosphorylation sites in a mixture of alpha-casein,
      beta-casein, and ovalbumin. The technique has potential for adaptations to
      proteome-wide analysis of protein phosphorylation.

PMID- 11507764
TI  - Analysis of fatty acids by graphite plate laser desorption/ionization time-of
      flight mass spectrometry.
AB  - Fatty acids obtained from triglycerides (trioelin, tripalmitin), foods (milk,
      corn oil), and phospholipids (phosphotidylcholine, phosphotidylserine,
      phosphatidic acid) upon alkaline hydrolysis were observed directly without
      derivatization by graphite plate laser desorption/ionization time-of-flight mass
      spectrometry (GPLDI-TOFMS). Mass-to-charge ratios predicted for sodium adducts of
      expected fatty acids (e.g. palmitic, oleic, linoleic and arachidonic acids) were
      observed without interference. Although at present no quantitation is possible,
      the graphite plate method enables a simple and rapid qualitative analysis of
      fatty acids.

PMID- 11507763
TI  - Rearrangement with formamide extrusion in the electrospray mass spectra of
      aminoacylbenzylamines.
AB  - Several aminoacylbenzylamines and their analogs were synthesized and analyzed by
      electrospray ionization mass spectrometry together with high-resolution and
      tandem mass spectrometric techniques. Fragment ions ([M + H - CH3NO](+)) were
      observed and attributed to a transfer of the benzyl group to the N-terminal amino
      group, leading to elimination of formamide. The proposed mechanism is supported
      by accurate mass measurements, and by experiments on deuterium labeling and
      variations of functional groups.

PMID- 11507765
TI  - Expression and regulation of the retinoic acid synthetic enzyme RALDH-2 in the
      embryonic chicken wing.
AB  - Retinaldehyde dehydrogenase type 2 (RALDH-2) is a major retinoic acid (RA)
      generating enzyme in the embryo. Here, we report immunolocalization of this
      enzyme (RALDH-2-IR) in the developing wings of stage 17-30 chicken embryos. RALDH
      2-IR is located in the area of the presumptive muscle masses, although it is not
      colocalized with developing muscle cells. RALDH-2-IR is located in tendon
      precursor cells and may be present in muscular connective tissue. We show that
      motor neurons and blood vessels, tissues showing RALDH-2-IR as they enter the
      limb, are capable of synthesizing and releasing RA in culture. RALDH-2-IR in the
      limb mesenchyme is under the control of both the vasculature and the motor
      innervation; it is decreased with denervation and increased with
      hypervascularization. RALDH-2-IR is present in the motor neuron pool of the
      brachial spinal cord, but this expression pattern is apparently not under the
      control of limb target tissues, RA in the periphery, or somitic factors. RA is
      known to be a potent inducer of cellular differentiation; we propose that locally
      synthesized RA may be involved in aspects of wing tissue specification, including
      cartilage condensation and outgrowth, skeletal muscle differentiation, and
      recruitment of smooth muscle cells to the vasculature.

PMID- 11507766
TI  - TGFbeta2 activation status during cardiac morphogenesis.
AB  - Transforming growth factor beta (TGFbeta) is secreted as a biologically inactive
      complex by many cell types in vitro, but little is known of TGFbeta's activation
      status in vivo. This study examined the in vivo expression of active and total
      (active + acid-activatable) TGFbeta2 in embryonic chicken hearts during cardiac
      morphogenesis (Hamburger-Hamilton stage 10-24). The concentration of TGFbeta2 was
      measured by an enzyme-linked immunoassay that recognized active TGFbeta2. Whole
      heart homogenates were either left untreated to measure active TGFbeta2 or
      treated with acid before assay to measure total (active + acid-activatable)
      TGFbeta2. Total TGFbeta2 concentration increased more than 16-fold between stage
      10/11 and stage 24. Active TGFbeta2 concentration was highest at stage 14/15, but
      overall remained relatively constant varying at most by 2.8-fold. When expressed
      relative to total TGFbeta2, the amount of active TGFbeta2 progressively declined
      from 70% in stage 10/11 hearts to 7% in stage 24 hearts. The distribution of
      active and total TGFbeta2 was examined by immunostaining with an antibody against
      active TGFbeta2. Before immunostaining, sections were either treated with acid or
      left untreated to determine the distribution of total and active TGFbeta2,
      respectively. Active TGFbeta2 immunostaining was first detected in the
      endothelium, myocardium, and cardiac jelly of stage 14 hearts. Acid treatment had
      no effect on the distribution or intensity of immunostaining at this stage.
      Faint, active TGFbeta2 immunostaining was restricted to the ventricular
      myocardium in stage 18 hearts. Acid treatment resulted in a marked increase in
      staining intensity in the ventricle, but no staining was observed in the atrium
      or outflow tract. In stage 24 hearts, faint active TGFbeta2 staining was detected
      in the ventricle before acid treatment. After acid treatment, patches of intense
      punctate stain were found in all regions of the embryonic heart. Increases in
      TGFbeta2 concentration and immunostaining intensity after acidification suggest
      that a significant amount of TGFbeta2 is in the latent form. Stage-dependent
      differences in activation status suggest that activation may be a developmentally
      regulated process in the chick heart and support the notion that activation is an
      important step in regulating TGFbeta actions in vivo.

PMID- 11507767
TI  - Induction of ureter branching as a response to Wnt-2b signaling during early
      kidney organogenesis.
AB  - Epithelial-mesenchymal tissue interactions play a central role in vertebrate
      organogenesis, but the molecular mediators and mechanisms of these morphogenetic
      interactions are still not well characterized. We report here on the expression
      pattern of Wnt-2b during mouse organogenesis and on tests of its function in
      epithelial- mesenchymal interactions during kidney development. Wnt-2b is
      expressed in numerous developing organs in the mouse embryo, including the
      kidney, lung, salivary gland, gut, pancreas, adrenal gland, and genital tubercle.
      Additional sites of expression include the branchial arches and craniofacial
      placodes such as the eye and ear. The data suggest that the expression of Wnt-2b
      is associated with organs regulated by epithelial-mesenchymal interactions. It is
      typically localized in the capsular epithelium or peripheral mesenchymal cells of
      organ rudiments, e.g., the perinephric mesenchymal cells in the region of the
      presumptive renal stroma in the developing kidney at E11.5. Functional studies of
      the kidney demonstrate that cells expressing Wnt-2b are not capable of inducing
      tubule formation but instead stimulate ureter development. Incubation of isolated
      ureteric buds on such cells supports bud growth and branching. In addition,
      recombination of Wnt-2b-pretreated ureteric bud tissue with isolated nephrogenic
      mesenchyme results in a recovery of organogenesis and the expression of
      epithelial genes within the reconstituted organ explant. Lithium, a known
      activator of Wnt signaling (Hedgepeth et al. [1997] Dev Biol 185:82-91), is also
      sufficient to promote ureter branching in the reconstituted kidney in a
      comparable manner to Wnt-2b signaling, whereas Wnt-4, which induces tubules,
      neither supports the growth of a ureteric bud nor leads to reconstitution of the
      ureteric bud with the kidney mesenchyme. We conclude that Wnt-2b may act in the
      mouse kidney as an early mesenchymal signal controlling morphogenesis of
      epithelial tissue, and that the Wnt pathway may regulate ureter branching
      directly. In addition, Wnt signals in the kidney differ qualitatively and are
      specific to either the epithelial ureteric bud or the kidney mesenchyme.

PMID- 11507768
TI  - In early development of the rat mRNA for the major myelin protein P(0) is
      expressed in nonsensory areas of the embryonic inner ear, notochord, enteric
      nervous system, and olfactory ensheathing cells.
AB  - The myelin protein P(0) has a major structural role in Schwann cell myelin, and
      the expression of P(0) protein and mRNA in the Schwann cell lineage has been
      extensively documented. We show here, using in situ hybridization, that the P(0)
      gene is also activated in a number of other tissues during embryonic development.
      P(0) mRNA is first detectable in 10-day-old embryos (E10) and is at this time
      seen only in cells in the cephalic neural crest and in the otic placode/pit. P(0)
      expression continues in the otic vesicle and at E12 P(0) expression in this
      structure largely overlaps with expression of another myelin gene, proteolipid
      protein. In the developing ear at E14, P(0) expression is complementary to
      expression of serrate and c-ret mRNAs, which later are expressed in sensory areas
      of the inner ear, while expression of bone morphogenetic protein (BMP)-4 and
      P(0), though largely complementary, shows small areas of overlap. P(0) mRNA and
      protein are detectable in the notochord from E10 to at least E13. In addition to
      P(0) expression in a subpopulation of trunk crest cells at E11/E12 and in Schwann
      cell precursors thereafter, P(0) mRNA is also present transiently in a
      subpopulation of cells migrating in the enteric neural crest pathway, but is down
      regulated in these cells at E14 and thereafter. P(0) is also detected in the
      placode-derived olfactory ensheathing cells from E13 and is maintained in the
      adult. No signal is seen in cells in the melanocyte migration pathway or in TUJ1
      positive neuronal cells in tissue sections. The activation of the P(0) gene in
      specific tissues outside the nervous system was unexpected. It remains to be
      determined whether this is functionally significant, or whether it is an
      evolutionary relic, perhaps reflecting ancestral use of P(0) as an adhesion
      molecule.

PMID- 11507769
TI  - Enzymes active in the areas undergoing cartilage resorption during the
      development of the secondary ossification center in the tibiae of rats ages 0-21
      days: I. Two groups of proteinases cleave the core protein of aggrecan.
AB  - The formation of a secondary ossification center in the cartilaginous epiphysis
      of long bones requires the excavation of canals and marrow space and, therefore,
      the resorption of cartilage. On the assumption that its resorption requires the
      lysis of the major cartilage component aggrecan, it was noted that the core
      protein may be cleaved in vitro by proteinases from two subfamilies: matrix
      metalloproteinases (MMPs) and aggrecanases. Such cleavage results in aggrecan
      being replaced by a fragment of itself referred to as a "G1-fragment." To find
      out if this cleavage occurs in the developing epiphysis of the rat tibia, the
      approach has been to localize the G1 fragments. For this purpose two neoepitope
      antisera were applied, one capable of recognizing the MMP-generated G1-fragment
      that bears the C-terminus ...FVDIPEN341 and the other capable of recognizing the
      aggrecanase-generated G1-fragment that carries the C-terminus ...NITEGE373. With
      the aid of these antisera, we report here that aggrecan cleavage is localized to
      newly developed sites of erosion. Thus, at 6 days of age, canals allowing the
      entry of capillaries are dug out from the surface of the epiphysis in a radial
      direction (stage I), whereas immunostaining indicative of aggrecan cleavage by
      MMPs appears at the blind end of each canal. The next day, the canal blind ends
      fuse to create a marrow space in the epiphysis (stage II), whereas immunostaining
      produced by MMPs occurs along the walls of this space. By 9 days, clusters of
      hypertrophic chondrocytes are scattered along the marrow space wall to initiate
      the formation of the secondary ossification center (stage III), where the
      resorption sites are unreactive to either antiserum. From the 9th to the 21st
      day, the center keeps on enlarging and, as the distal wall of the marrow space
      recedes, it is intensely immunostained with both antisera indicating that both
      MMPs and aggrecanases are involved in this resorption. We conclude, that both
      enzyme subfamilies contribute to the lysis of aggrecan. However, the results
      suggest that the respective subfamilies target different sites and even stages of
      development in the tissue, suggesting some diversity in the mode of aggrecan
      lysis during the excavation of a secondary ossification center.

PMID- 11507770
TI  - Enzymes active in the areas undergoing cartilage resorption during the
      development of the secondary ossification center in the tibiae of rats aged 0-21
      days: II. Two proteinases, gelatinase B and collagenase-3, are implicated in the
      lysis of collagen fibrils.
AB  - In the transformation of the cartilaginous epiphysis into bone, the first
      indication of change in the surfaces destined for resorption is the cleavage of
      aggrecan core protein by unidentified matrix metalloproteinases (MMPs) (Lee et
      al., this issue). In cartilage areas undergoing resorption, the cleavage leaves
      as superficial, 6-microm-thick band of matrix, referred to as "pre-resorptive
      layer." This layer harbors G1-fragments of the aggrecan core protein within a
      framework of collagen-rich fibrils exhibiting various stages of degeneration.
      Investigation of this layer in every resorption area by gelatin histozymography
      and TIMP-2 histochemistry demonstrates the presence of an MMP whose
      histozymographic activity is inhibited by such a low dose of the inhibitor CT1746
      as to identify it as gelatinase A or B. Attempts at blocking the histozymographic
      reactions with neutralizing antibodies capable of inhibiting either gelatinase A
      or B reveals that only those against gelatinase B do so. Immunostaining of
      sections with anti-gelatinase B IgG confirms the presence of gelatinase B in
      every pre-resorptive layer, that is, at the blind end of excavated canals (stage
      I; 6-day-old rats), at sites along the walls of the forming marrow space (stage
      II; 7days), at sites within the walls of this space as it becomes the
      ossification center (stage III; 9 days) and along the wall of the maturing center
      (stage IV; 10-21 days). We also report the presence of collagenase-3 in precisely
      the same sites, possibly as active enzyme, but this remains to be proven. Because
      the results reveal that collagenase-3 is present beside gelatinase B in every pre
      resorptive layer and, because these sites exhibit various signs of degradation
      including fibrillar debris, reduction in fibril number, or overt loss, we propose
      that gelatinase B and collagenase-3 mediate the lysis of this pre-resorptive
      layer-most likely through a cooperative attack leading to the disintegration of
      the collagen fibril framework.

PMID- 11507771
TI  - Fibulin-2 expression marks transformed mesenchymal cells in developing cardiac
      valves, aortic arch vessels, and coronary vessels.
AB  - Previous studies showed that extracellular matrix protein, fibulin-2, is
      expressed during epithelial-mesenchymal transformation in the endocardial cushion
      matrix during embryonic heart development. Our current study revealed that, in
      addition to the cardiac valvuloseptal formation, fibulin-2 is synthesized by the
      smooth muscle precursor cells of developing aortic arch vessels and the coronary
      endothelial cells that are originated from neural crest cells and epicardial
      cells, respectively. In the cardiac valves and the aortic arch vessels, fibulin-2
      expression shows robust up-regulation when the transformed mesenchymal cells
      migrate into the existing extracellular matrix. In the epicardium, epicardial
      cells produce fibulin-2 upon their migration over the myocardial surface and its
      expression persists throughout coronary vasculogenesis and angiogenesis. Fibulin
      2 is produced by the endothelial cells of coronary arteries and veins but not by
      the capillary endothelial cells in the myocardium. Thus, fibulin-2 not only
      uniquely marks the transformed mesenchymal cells during mouse embryonic
      cardiovascular development, but also indicates vascular endothelial cells of
      coronary arteries and veins in postnatal life.

PMID- 11507772
TI  - Localization of Lutheran, a novel laminin receptor, in normal, knockout, and
      transgenic mice suggests an interaction with laminin alpha5 in vivo.
AB  - Laminins are major components of all basement membranes. One laminin that has
      garnered particular interest, due to its widespread expression pattern and
      importance during development, is the laminin alpha5 chain. In vitro studies have
      suggested that the Lutheran blood group glycoprotein/basal cell adhesion molecule
      (Lu), an Ig superfamily transmembrane protein, is a receptor for laminins
      containing the alpha5 chain. However, there are no in vivo studies showing that
      these proteins are capable of interacting in tissues. We have isolated the mouse
      ortholog of Lu and characterized its expression and localization in mouse
      tissues. Lu was primarily found on the basal surface of epithelial cells and on
      muscle cells adjacent to basement membranes containing laminin alpha5. In
      addition, there was both a dramatic reduction in the basal concentration of Lu in
      mice lacking laminin alpha5, and a significant increase in Lu protein in
      transgenic mice overexpressing laminin alpha5. Together, these data provide the
      first in vivo evidence for an interaction between Lu and laminin alpha5 and
      support the hypothesis that Lu is a laminin alpha5 receptor. We propose that
      laminin alpha5 is involved in concentrating Lu on the basal surface of epithelial
      cells. This may be one mechanism by which basement membrane signals are
      transmitted to the cell.

PMID- 11507773
TI  - Abnormal neural crest cell migration after the in vivo knockdown of tenascin-C
      expression with morpholino antisense oligonucleotides.
AB  - A key feature of vertebrate development is the formation of the neural crest. In
      the trunk, neural crest cells delaminate from the neural tube shortly after the
      fusion of the neural folds and migrate ventrally along specific pathways to form
      the neurons and glia of the peripheral nervous system. As neural crest cells
      leave the neural tube during the initial stages of their migration, they express
      the extracellular matrix glycoprotein tenascin-C, which is also found in the
      stroma of many tumors. We have studied the possible role for tenascin-C during
      neural crest morphogenesis in vivo by microinjecting tenascin-C morpholino
      antisense oligonucleotides into the lumen of the avian neural tube in ovo and
      electroporating the morpholino antisense oligonucleotides into the precursors of
      the neural crest. After 24 hr, tenascin-C immunostaining is reduced around the
      dorsal neural tube in the experimental microinjected embryos (12 of 13) but not
      in embryos microinjected with control morpholino antisense oligonucleotides (n =
      3) or subjected to electroporation only (n = 2). In each of the 12 tenascin-C
      knockdown embryos neural crest cells are seen ectopically in the lumen of the
      neural tube and in the neuroepithelium; cells that do leave the neural tube after
      the microinjection fail to disperse laterally from the surface of the neural tube
      into the somites. The observation that neural crest cells must express tenascin-C
      to migrate normally is consistent with a role for this glycoprotein in
      contributing to the invasive behavior of neural crest cells.

PMID- 11507774
TI  - Expression and potential role of angiopoietins and Tie-2 in early development of
      the mouse metanephros.
AB  - Angiopoietins (Ang) are secreted factors which bind the Tie-2 receptor and
      modulate endothelial growth. This signalling system is known to be expressed in
      later stages of maturation of the mouse metanephros, the adult kidney precursor.
      In this study, by using reverse transcription polymerase chain reaction and
      Northern and Western blotting, we demonstrated that Ang-1, Ang-2, and Tie-2 were
      expressed during early metanephrogenesis when interstitial and glomerular
      capillaries begin to form. By using immunohistochemistry, embryonic kidney
      capillaries in the interstitium and glomeruli expressed Tie-2 at a later stage of
      differentiation compared with vascular endothelial growth factor receptor-2 and
      platelet-endothelial cell adhesion molecule. Addition of 200 ng/ml Ang-1 to
      explanted embryonic day (E) 12.5 metanephroi increased the proportion of vascular
      glomeruli that formed during 1 week in culture. These results are consistent with
      the hypotheses that Tie-2 has a role in vascular growth in the early stages of
      mammalian nephrogenesis and that Tie-2 activation may maintain the integrity of
      recently formed interstitial and glomerular vessels.

PMID- 11507775
TI  - Can purchasers correct the course? New roles, new responsibilities.
AB  - A health care analyst-writer explains the critical components for the health care
      purchasing system of tomorrow and lays out an action plan for effectively facing
      its challenges.

PMID- 11507776
TI  - Can employers rewrite the rules for health care coverage?
AB  - Caught between rising costs and widespread frustration with managed care,
      employers struggle with a system beyond any simple remedy.

PMID- 11507777
TI  - Where's the leadership for quality measurement?
AB  - With performance measurement in gridlock, purchasers look to disease intervention
      to improve medical care. Consumers, meanwhile, are left with member surveys and
      sketchy info on providers.

PMID- 11507778
TI  - Carving new roles for the health care consumer.
AB  - Employees are becoming increasingly vocal about their health care needs, but few
      face the financial consequences of their treatment decisions. That dichotomy must
      be resolved, analysts agree, even as they argue about how to do it.

PMID- 11507779
TI  - Healthy people 2010: checkup for the nation.
AB  - The government's action plan to promote health and prevent disease in the first
      decade of the new millennium.

PMID- 11507780
TI  - Purchaser attitudes and health care decision-making, 2000.

PMID- 11507781
TI  - Physicians vs. managed care. Can't they all just get along?
AB  - As the finger-pointing escalates between physicians and health plans, impatient
      employers seek new ways to assert the power of the purchaser.

PMID- 11507782
TI  - Tug of war for a new millennium.
AB  - Left dead in the water in 1999, the reforms that would reshape medicare and
      mandate patient protections have now drifted into election-year partisanship.

PMID- 11507783
TI  - Health care is high on states' agendas, too.
AB  - Among the concerns in state legislatures: HMO solvency, drug costs, medical
      privacy.

PMID- 11507784
TI  - On voters' minds: health care and the uninsured.
AB  - In a new Kaiser/Harvard survey, more than one in four voters cited health care as
      the top issue.

PMID- 11507785
TI  - Job-based health insurance. Who has the duty to lead?
AB  - A noted medical ethicist argues that only the business community has the
      collective power and resources to create a "sustainable medicine" for the
      nation's health care. But will employers have sufficient incentive and motivation
      to do so?

PMID- 11507786
TI  - Infusion Nursing Code of Ethics.

PMID- 11507787
TI  - Quality of life of cancer patients receiving home infusion services. A pilot
      study.
AB  - Quality of life (QOL) has become an increasingly popular outcome measure in
      healthcare during the past 20 years. Despite its growing popularity, there is no
      professional agreement regarding definitions, conceptual models, or
      instrumentation. Many patient populations have been studied, but there has been
      minimal investigation of health-related QOL in patients receiving homecare,
      especially home infusion services. This study, which used the Ferrans and Powers
      Cancer Index III, explored QOL in cancer patients receiving home infusion
      therapies for at least 30 days. Although no statistically significant
      improvements in QOL were identified, the study was useful in pinpointing relevant
      issues for future QOL investigation in homecare and home infusion.

PMID- 11507788
TI  - Controversial issues in the care and maintenance of vascular access devices in
      the long-term/subacute care client.
AB  - The aging population provides a unique challenge for the initiation and
      maintenance of infusion therapy. This article will highlight three common but
      controversial issues that have been observed by this author in the long
      term/subacute care realm of infusion therapy: 1) the failure to maintain a
      sterile dressing over the catheter insertion site; 2) the use of heparin to
      maintain patency of the peripheral infusion device; and 3) the routine
      replacement of peripheral i.v. catheters. Several factors that contribute to the
      controversies will be discussed, along with some associated negative and positive
      outcomes.

PMID- 11507789
TI  - Treatment of inflammatory bowel disease in the adolescent.
AB  - Inflammatory bowel disease (IBD) is a chronic condition that often presents in
      adolescence. The characteristic manifestations, exacerbations, and treatment of
      the disease affect the adolescent's physical, physiological, and psychological
      development. Body image, self-esteem, and dependence/independence issues may lead
      to noncompliance, further complicating the disease process and its management.
      This article will review IBD and present treatment options and interventions in
      the care of the adolescent with IBD.

PMID- 11507790
TI  - Recognition and management of inferior wall myocardial infarctions and right
      ventricular infarcts.
AB  - Cardiovascular disease is a predominant health problem in the United States.
      Annually, more than 6 million people experience an acute myocardial infarction
      (MI). Right ventricular infarct (RVI) occurs in approximately one third of all
      patients who present with an inferior wall myocardial infarction (IWMI). The
      aggressive initial treatment of IWMI with RVI may improve morbidity and
      mortality. Thus, it is essential to understand the different modalities used to
      treat a right and left ventricular MI.

PMID- 11507791
TI  - Prevention of HIV among adolescents.
AB  - Adolescents are at risk for HIV primarily through their sexual behavior. A
      comprehensive prevention strategy includes a national HIV campaign based on
      social marketing principles; targeted social marketing, intensive skill building,
      and sexually transmitted disease control programs for youth at high risk;
      programs targeting institutions (e.g., school health clinics), providers, and
      parents; and interventions to identify and reduce risk acts among seropositive
      youth. The U.S. focus for HIV prevention has been single-session educational
      classes (an ineffective strategy) or intensive multi-session, small-group
      interventions for youth at high risk (demonstrated to increase condom use by
      about 30%). There is a need to expand the range, modalities, and dissemination of
      HIV prevention programs nationally, to recognize (especially by policymakers)
      limitations of abstinence programs, and to increase early detection of HIV among
      youth.

PMID- 11507792
TI  - Adolescent growth in new forms of problem behavior: macro- and micro-peer
      dynamics.
AB  - Longitudinal data from an at-risk sample were used to analyze individual linear
      trend scores for each of three new forms of problem behavior that emerges during
      the interval from age 10 through 18 years. Growth in substance use, health
      risking sexual behavior and police arrests defined a latent construct for growth
      in adolescent problem behavior. A structural equation model (SEM) showed a
      significant path from early involvement with deviant peers to a latent construct
      for growth in new forms of antisocial behavior. A second SEM showed that the
      contribution of early involvement to later growth was mediated by a latent
      construct for deviancy training assessed at age 14 years. The relative rates of
      reinforcement for deviancy, amount of time spent with deviant peers, and deviancy
      level of the peer network defined a deviancy training construct that accounted
      for 53% of the variance in later growth in new forms.

PMID- 11507793
TI  - The value of interrupted time-series experiments for community intervention
      research.
AB  - Greater use of interrupted time-series experiments is advocated for community
      intervention research. Time-series designs enable the development of knowledge
      about the effects of community interventions and policies in circumstances in
      which randomized controlled trials are too expensive, premature, or simply
      impractical. The multiple baseline time-series design typically involves two or
      more communities that are repeatedly assessed, with the intervention introduced
      into one community at a time. It is particularly well suited to initial
      evaluations of community interventions and the refinement of those interventions.
      This paper describes the main features of multiple baseline designs and related
      repeated-measures time-series experiments, discusses the threats to internal
      validity in multiple baseline designs, and outlines techniques for statistical
      analyses of time-series data. Examples are given of the use of multiple baseline
      designs in evaluating community interventions and policy changes.

PMID- 11507794
TI  - Enhancing the educational achievement of at-risk youth.
AB  - This study examined a non-school program aimed at enhancing the educational
      performance of economically disadvantaged early adolescents who live in public
      housing. The educational enhancement program included discussions with adults,
      writing activities, leisure reading, homework, helping others, and games using
      cognitive skills. A three-arm research design juxtaposed program youth who
      received educational enhancements with comparison youth in affiliated facilities
      who did not receive the program and with control youth in other community
      programs without educational enhancements. From youths, follow-up data collected
      2 1/2 years after baseline revealed uniformly positive outcomes for program youth
      on measures of reading, verbal skills, writing, and tutoring. Teacher reports at
      final follow-up favored program and comparison youth over controls on measures of
      reading, writing, games, overall school performance, and interest in class
      material. School grades were higher for program youth than for comparison and
      control youth for reading, spelling, history, science, and social studies.
      Overall grade averages were higher for program youth versus comparisons and
      controls, as was school attendance. Study data lend empirical support to the
      provision of educational enhancements in non-school settings for at-risk youths.

PMID- 11507795
TI  - Relationship between bond strengths and nanoleakage: evaluation of a new
      assessment method.
AB  - PURPOSE: To test if there was a correlation between resin-dentin bond strengths
      and nanoleakage of total etch and self-etching primer bonding systems. MATERIALS
      AND METHODS: Ten extracted third molars were ground flat with 600 grit SIC paper
      under running water to expose middle dentin. Clearfil Liner Bond 2V or Single
      Bond was applied to the dentin surface according to the manufacturers'
      instructions. A crown was built-up with Clearfil AP-X resin-based composite, and
      the specimens stored in water for 24 hrs at 37 degrees C. The bonded assemblies
      were cut mesiodistally perpendicular to the interface into approximately 0.7 mm
      thick slabs, and trimmed for microtensile bond strength testing. Alternate slices
      from each tooth were either entirely double-coated with nail varnish leaving a
      0.5 mm window around the interface, or left uncoated to be immersed in water for
      13 hrs as the control. The varnished (experimental) slabs were immersed in 50%
      AgNO3 for 1 hr, and then immersed in a photo developing solution for 12 hrs. All
      specimens were subjected to microtensile bond test at a crosshead speed of 1
      mm/min. After debonding, the specimens were embedded in epoxy resin and observed
      under a confocal laser scanning microscope for determination of lateral silver
      penetration within the interface. Silver penetration was further analyzed under
      the SEM. Data were analyzed with one- and two-way ANOVA, Fisher's PLSD test (P <
      0.05), and regression analysis. RESULTS: The bond strengths of Clearfil Liner
      Bond 2V and Single Bond were not significantly different (P > 0.05); however the
      bond strengths of the specimens that were soaked in 50% AgNO3 for 1 hr
      significantly increased (P < 0.01). No correlation was observed between bond
      strengths and nanoleakage.

PMID- 11507796
TI  - In vivo bonding mechanism of an experimental dual-cure enamel-dentin bonding
      system.
AB  - PURPOSE: To evaluate, in vivo, the formation of hybrid layer, resin tags and
      adhesive lateral branches, by an experimental dual-curing "one-bottle" enamel
      dentin bonding system. MATERIALS AND METHODS: The new dentin adhesive (Excite
      DSC) was tested in five Class V restorations placed in vital, periodontally
      compromised teeth. The experimental bonding system was used in combination with a
      flowable composite. After 1 wk the teeth were extracted and processed for SEM
      evaluation. All the samples were split-fractured along their long axis. Half of
      the samples were used to evaluate hybrid layer formation and the other half to
      examine the morphology of resin tags. RESULTS: The experimental adhesive system
      showed a micromechanical bonding mechanism to conditioned dentin with formation
      of a hybrid layer, resin tags and adhesive lateral branches. SEM photomicrographs
      of the decalcified samples showed a high density of resin tags and uniform
      distribution along the cavity walls.

PMID- 11507797
TI  - Determining the direction of shrinkage in dental composites by changes in surface
      contour for different bonding configurations.
AB  - PURPOSE: To determine if polymerization shrinkage of a light-cured composite is
      directed toward the light source, and if a relationship exists between C-factor
      and magnitude of deflection. MATERIALS AND METHODS: Either a self-cured composite
      or light-cured composite each was placed in an experimental model of composite
      cured in a glass ring. Changing the surface area prepared for bonding within the
      cavity preparation produced three different C-factors (the ratio of bonded to
      unbonded surface areas): 0, 1.9, and 4.8. Profilometer tracings were obtained,
      and the largest deviation from the height of the glass ring was reported. An
      uncured control sample also was evaluated and showed a linear tracing with
      fluctuations of less than 0.5 micron. The specimens were then cut in half and
      examined by scanning electron microscope. RESULTS: The top (unbonded) surface
      exhibited a concave shrinkage profile with the greatest deflection at the center.
      The magnitude of deflection at the center increased as the cavity's C-factor
      increased from 31 microns (C = 0) to 57 microns (C = 4.8). The bottom (unbonded)
      surface, similarly formed a concave surface. When the composite was bonded to the
      glass, fractures in the glass wall near the glass-composite interface were
      observed.

PMID- 11507798
TI  - Use of spore tests for quality assurance in infection control.

PMID- 11507799
TI  - Condyloma acuminatum of the floor of the mouth.

PMID- 11507800
TI  - A comparative 3-month clinical investigation of the safety and efficacy of a
      battery-operated and a rechargeable oscillating-rotating power toothbrush.
AB  - PURPOSE: To compare the safety and efficacy of two oscillating-rotating power
      toothbrushes, the rechargeable Braun Oral-B D8 and the battery-powered Colgate
      Actibrush. MATERIALS AND METHODS: This was a randomized, examiner-blind, parallel
      group study, carried out over 3 months of product use, involving a total of 113
      healthy subjects with a plaque score of > or = 1.5 and a gingivitis score of > or
      = 1.1. Subjects were given written and verbal instructions in the use of their
      respective power brushes and were told to brush twice per day. At baseline, hard
      and soft tissues were examined, and plaque scores and gingival scores were
      recorded after 12-18 hrs of no oral hygiene. Subjects returned after 3 months, at
      which time soft and hard tissues were re-examined and plaque and gingivitis
      scores were recorded. RESULTS: No evidence was found of soft or hard tissue
      trauma and both brushes were considered to be safe when used according to the
      manufacturers' instructions. After 3 months, whole mouth plaque scores had
      decreased by 7% in the D8 group but had increased by 4.3% in the Actibrush group.
      The decrease from baseline in the D8 group was statistically significant, but the
      increase in the Actibrush group was not. The difference between the two groups
      was statistically significant both for the whole mouth and all individual sites.
      Whole mouth gingivitis scores were also reduced significantly from baseline in
      both groups, by 22.5% in the D8 group and by 17.5% in the Actibrush group. For
      whole mouth scores and all individual sites (interproximal, buccal and lingual),
      the D8 was significantly more effective than the Actibrush.

PMID- 11507801
TI  - Effect of carbamide peroxide bleaching agents on the physical properties and
      chemical composition of enamel.
AB  - PURPOSE: To evaluate the effect of two commercially available carbamide peroxides
      bleaching agents, Opalescence and Nite-White, in concentrations of 10, 15 and
      16%, on enamel. MATERIALS AND METHODS: Vickers hardness measurements (VH) were
      made at the surface and 110 microns below the surface on human enamel samples
      that were treated for 5 or 10 days, 6 hrs/day. Furthermore, infrared
      spectrophotometry (IR), Fourier transform infrared spectrophotometer (FTIR) and X
      ray diffraction (XRD) measurements were performed after the VH measurements were
      completed. RESULTS: Using a one-way ANOVA, statistically significant differences
      in VH could be established between surface and subsurface VH values. For all
      groups, including the control group, the surface VH values were statistically
      significantly higher than subsurface VH. IR, FTIR and XRD established a change
      from hydroxyapatite to primary calcium ortho phosphate [Ca(H2PO4)2] for all
      experimental groups except for 10% Opalescense tested for 5 or 10 days.

PMID- 11507802
TI  - Effects of 10% carbamide peroxide bleaching materials on enamel microhardness.
AB  - PURPOSE: To evaluate the microhardness of enamel treated with two different 10%
      carbamide peroxide bleaching materials at different time intervals. MATERIALS AND
      METHODS: Two bleaching agents were analyzed: Opalescence (OPA) and Rembrandt
      (REM). The control group (CON) consisted of dental fragments maintained in
      artificial saliva. Bleaching was accomplished for 8 hrs per day and stored during
      the remaining time in an individual recipient with artificial saliva. Enamel
      microhardness testing was performed before the initial exposure to the treatments
      and after 1, 7, 14, 21, 28, 35 and 42 days. RESULTS: The ANOVA, followed by the
      Bartlet and Tukey tests, showed significant differences for treatments (P <
      0.00001) from day 7-day 42. From the 7th to the 14th day, OPA presented an
      increase of enamel microhardness over time while REM presented a decrease of
      microhardness. Statistical differences were not found between REM and the control
      group (OPA > CON = REM). From the 21st-35th day, enamel fragments bleached with
      OPA and REM presented a decrease of microhardness. Statistical differences of
      microhardness were verified among all the treatments (OPA > CON > REM). On the
      day 42, statistical differences were not found between OPA and the control group,
      but they were found between REM and the control group (OPA = CON > REM). The
      polynomial regression showed an increase of microhardness for OPA until the 21st
      day, followed by a decrease of microhardness up to the 42nd day. A decrease of
      microhardness for REM was verified. There were alterations in enamel
      microhardness as a function of bleaching time when using the two different 10%
      carbamide peroxide whiteners. Over a 42-day treatment time, bleaching with REM
      agent caused a decrease in enamel microhardness. The OPA agent initially
      increased the microhardness, then returned to the control level. Different
      bleaching materials with the same concentration of carbamide peroxide have
      different effects on the enamel.

PMID- 11507803
TI  - Incidence of fractures and lifetime predictions of all-ceramic crown systems
      using censored data.
AB  - PURPOSE: To determine Kaplan-Meier survival estimates and Weibull lifetime
      predictions for four all-ceramic crown systems from long-term data (> 5 yrs).
      MATERIALS AND METHODS: Single unit crowns of Cerestore (n = 30), Dicor (n = 30),
      Hi-Ceram (n = 22) and In-Ceram (n = 68) were placed in 95 patients treated in a
      university clinic. They were cemented using glass-ionomer (GI) for Cerestore,
      zinc phosphate (ZP) for Dicor, and 75% ZP (n = 51), 20% GI (n = 13) and 5% resin
      based cement (n = 4) for In-Ceram crowns. The follow-up times were 8 yrs for
      Cerestore, 7 yrs for Dicor, 6 yrs for Hi-Ceram and 5 yrs for In-Ceram. The
      statistical analyses were based on censored data sets. A progressively censored
      Weibull distribution allowing for lifetime predictions beyond the actual
      observation time was used as well as the Kaplan-Meier Survival Product Limit
      Estimate (PLE), which provides survival estimates up to the maximum time of
      follow-up. RESULTS: Cerestore, Dicor and Hi-Ceram demonstrated molar fractures in
      the first 2 yrs, whereas for In-Ceram these occurred during the third and fourth
      year of the study. The Kaplan-Meier Survival PLE was 69% for Cerestore at 8 yrs,
      86% for Dicor at 7 yrs, 81% for Hi-Ceram at 6 yrs, 92% for In-Ceram at 5 yrs. The
      predicted Weibull characteristic time T0 (time at which 63% of the restorations
      would have failed) was 23 yrs for Cerestore, 34 yrs for Dicor, 31 yrs for Hi
      Ceram, and 16 yrs for In-Ceram. However, when using data sets arbitrarily limited
      to the three first years of follow-up, T0 decreased significantly for Cerestore,
      Dicor and Hi-Ceram due to the number of early fractures. Such Weibull lifetime
      data illustrate the risk of predicting long-term (> 5 yrs) survival using short
      term (< or = 3 yrs) data on ceramic restorations, which exhibit fracturing in the
      initial years.

PMID- 11507804
TI  - Wear of luting materials with titanium retainer.
AB  - PURPOSE: The purpose of this study was to investigate the wear resistance of
      prosthodontic luting materials with a titanium framework by means of an in vitro
      three-bodied wear-testing device. MATERIALS AND METHODS: The surfaces of flat
      cast titanium disks were blasted with 50 microns alumina. Placing a 50 microns
      masking tape on the plane surface, the disks were bonded with five luting
      materials. The axial surfaces of the bonded disks were ground flat with 600 grit
      silicon-carbide paper, and then cyclically loaded (75.6 N, 1.2 Hz) by a chewing
      simulator for 400,000 cycles. The distance between titanium and cement surfaces
      was measured in micrometers by means of a profilometer to determine delta wear,
      and the surface texture was evaluated with a scanning electron microscope.
      RESULTS: The delta wear measurement showed that the resistance of Super-Bond
      Opaque adhesive was significantly higher than Panavia Fluoro adhesive and Fuji I
      cement after 400,000 wear cycles. No significant differences were detected among
      Super-Bond Opaque adhesive, Super-Bond adhesive, and All-Bond adhesive. Visually,
      continuity with the titanium framework was observed when the titanium disks were
      luted with resin systems.

PMID- 11507805
TI  - Early bond strength and durability of bond between a ceramic material and
      chemically-cured or dual-cured resin luting agent.
AB  - PURPOSE: To evaluate the influence of the different polymerization types of two
      chemically-cured (Panavia 21 and Super-Bond C&B) and three dual-cured (Panavia
      Fluoro Cement, Clapearl DC, and Vita Cerec Duo Cement) resin luting agents on the
      early bond strengths and durability of bond to a Cerec 2 ceramic material.
      MATERIALS AND METHODS: The Cerec 2 ceramic specimens were prepared with No. 600
      silicon carbide paper and their surfaces were etched with phosphoric acid gel,
      and applied with silane coupling agent. Two sizes of specimens were then bonded
      together with each of the five luting agents. Shear bond tests were performed 10
      mins or 20 mins after preparing specimens, storage in water at 37 degrees C for
      24 hrs, and/or 20,000 thermocycles between 4 degrees C and 60 degrees C water
      baths. RESULTS: The specimens bonded with one of the three dual-cured resin
      luting agents showed almost the same shear bond strengths for all four storage
      conditions. However, two chemically-cured resin luting agents exhibited much
      lower shear bond strengths at 10- and 20-min intervals than at 0 and 20,000
      thermocycles. Three dual-cured resin luting agents showed significantly higher
      bond strengths than two chemically-cured resin luting agents at 10- and 20-min
      intervals.

PMID- 11507806
TI  - The use of oxalate to reduce dentin permeability under adhesive restorations.
AB  - PURPOSE: To test a novel approach to reducing dentin permeability that localizes
      occlusion of dentin tubules by calcium oxalate crystals to the subsurface without
      lowering resin bond strengths to oxalate-treated dentin surfaces. MATERIALS AND
      METHODS: Flat dentin surfaces of extracted human third molars were etched with a
      mass fraction of 32% phosphoric acid (Bisco) for 15 s and rinsed. Half of the
      surface was treated with a potassium oxalate gel (mass fraction of 3%
      monopotassium monohydrogen oxalate) for 2 mins. The entire surface was then moist
      bonded with either One Step (OS) or Scotchbond Multi-Purpose (SB) adhesive
      systems. A resin-based composite (Z-100) buildup was made over the entire
      surface. After storage for 24 hrs in distilled water, the teeth were
      longitudinally sectioned to separate the oxalate-treated half from the untreated
      (control) half. Each half was serially sectioned into several 0.7 mm thick slabs
      which were then trimmed to an hour-glass shape to reduce the bonded area to
      approximately 0.8 mm2 and tested in tension. Pre- and post-treatment hydraulic
      conductance (Lp) of dentin was determined using dentin discs with a standard
      protocol. SEM images were obtained to examine the effects of treatment both on
      the dentin surface and along the tubules beneath the surface. The bonded
      interface was also examined by SEM. RESULTS: Treating etched dentin discs with
      the oxalate gel caused significant reduction of the Lp of dentin (80% reduction,
      P < 0.05). There were no statistically significant differences between bond
      strengths of oxalate-treated and untreated surfaces for either adhesive system.
      OS resulted in a bond strength of 25.8 +/- 9.2 MPa to untreated and 27.8 +/- 8.9
      MPa to oxalate treated surfaces (P > 0.05). SB showed bond strengths of 22.9 +/-
      7.9 MPa and 22.9 +/- 9.6 MPa to untreated and treated surfaces, respectively (P >
      0.05). SEM images showed that the application of potassium oxalate gel on etched
      dentin resulted in the formation of crystals inside the tubules rather than on
      the surface. Examination of the bonded interfaces demonstrated that the crystal
      formation inside the tubules did not compromise the formation of a typical hybrid
      layer on the top of dentin surfaces. Resin monomers penetrated into the tubules
      filling the spaces around the crystals forming resin tags with a jagged-like
      feature.

PMID- 11507807
TI  - Three-year clinical evaluation of composite and ceramic inlays.
AB  - PURPOSE: To evaluate the 3-yr clinical performance of composite and ceramic
      inlays in posterior teeth. MATERIALS AND METHODS: 47 composite inlays (Tetric,
      Blend-a-Lux, Pertac) and 24 ceramic inlays (Empress) were placed by seven student
      operators under supervision of an experienced dentist. Clinical assessment of 58
      inlays (81.7%) was performed after 3 yrs using amodified USPHS criteria and
      statistically analyzed with Mann-Whitney U test and Fisher's exact test. RESULTS:
      A total of 100% of the ceramic inlays and 89% of the composite inlays were
      assessed to be clinically excellent or acceptable. Three composite inlays failed
      during the first yr and one had to be replaced during the second evaluation
      period. All composite inlay failures were recorded on molars, revealing a
      significantly higher failure rate compared with premolars (Fisher's test, P =
      0.041). Ceramic inlays revealed a significantly better "anatomic form of the
      surface" (P = 0.027) and "integrity of the restoration" (P = 0.035). Inlays in
      small cavities performed better for "marginal integrity" (P = 0.033) and
      "discoloration at the margin" (P = 0.038).

PMID- 11507808
TI  - Ward managers' attitudes towards external consultants in Ashworth, a special
      hospital, 1992-1994.
AB  - This case study elaborates the aftermath of the Blom-Cooper Inquiry (1992), which
      forced the special hospital, Ashworth, into a radical 'culture change'. To this
      end, two groups of external consultants--a management consultancy and a
      professional task force--were introduced into the hospital. Newly established
      ward managers were to spearhead the organizational change by bringing social and
      clinical order to the wards over which the higher management had lost control.
      Few studies have mapped out the interaction between segments of an organization
      and expert outsiders. In this study, the interaction of the ward manager to the
      newly appointed external management consultancy and task force was analysed. It
      was clear that ward managers rated poorly the efforts of the management
      consultancy and task force--it was considered that they were not giving value for
      money. The task force rated slightly more favourably than the management
      consultancy. The fact that the management consultancy did not have ward
      credibility in this closed forensic setting was attributed to low prestige. The
      management consultancy also failed to fulfill the organizational ambitions of
      ward managers, who wished to be central to the hospital's major decision-making
      process.

PMID- 11507809
TI  - The performance impact of context in TQM implementation: the nursing facility
      industry.
AB  - This study develops a model and empirically assesses how# organizational context
      mediates the impact of total quality management (TQM) implementation on perceived
      performance in the nursing facility industry. Outcomes are analysed for
      financial, human resources and resident-care performance. Contextual factors
      related to TQM implementation include managerial control, reward systems,
      organizational structure and the extent of implementation. Duration of TQM
      implementation is included as a control variable. Benchmarking has a positive
      impact on financial outcomes, and the extent of TQM implementation and required
      reporting of quality improvement activity results have a positive impact on both
      financial and human resources performance. The presence of a Quality Steering
      Council has a positive impact on financial performance, but only among larger
      facilities.

PMID- 11507810
TI  - Programme approach to managing informed commissioning.
AB  - The objective of this paper is to examine possible organizational reasons for why
      UK NHS commissioners have not adopted programme budgeting and marginal analysis
      (PBMA). This is despite increasing evidence of discontent with current
      commissioning and priority-setting processes, increasing research evidence
      demonstrating the potential of PBMA and support for the principles of PBMA. Two
      separate semistructured surveys of the views of commissioning decision-makers on
      the use of PBMA were carried out at Grampian Health Board and Newcastle & North
      Tyneside Health Authority. Twenty-nine decision-makers were interviewed. Both
      surveys found common barriers to implementation of PBMA, described by respondents
      as 'institutional inertia'. These were the reactive rather than proactive
      environment; the fear of 'unnecessary' explicitness; an aversion to unilateral
      innovation in the current NHS environment; and the demand for concrete evaluation
      evidence. It is concluded that these qualitative surveys have small samples and
      cannot claim to be representative. It may be significant that many issues were
      common to both surveys carried out separately in organizations. It is unlikely
      that NHS commissioning will independently adopt techniques such as PBMA, given
      the current commissioning environment and organizational structures.
      Implementation strategies and future research on such commissioning innovations
      may need to focus on institutions as well as the interventions.

PMID- 11507811
TI  - The effect of medical work groups on hospital resource use.
AB  - This study tests the ability of medical work groups to overcome coordination
      problems related to group decision-making in allocating clinical resources to
      inpatients. The study was conducted over a 32-month period in two medium-sized
      acute-care hospitals located in Montreal, Quebec, Canada. The data were collected
      by hand from the medical charts of 10,456 patients in the surgical and medical
      departments. The Linear Structural Relations (LISREL) approach was employed to
      address the work-group issue using a task contingent model of work-group
      organization. In this model, the nature of the task is fundamental because its
      level of complexity determines both the organization of the work group and the
      use of resources. Medical work-group mechanisms should be efficient to the extent
      that resource utilization is explained solely by task characteristics rather than
      by work-group structure. In this study, the following two major organizational
      concepts were used as factors to explain resource use: task characteristics and
      work-group characteristics. Our analysis confirmed the main points of the task
      contingency theory as applied to the field of medicine. First, the results
      confirm that resource utilization is explained mainly by task complexity. Second,
      they confirm that medical work groups modulate their structures on the basis of
      task characteristics and do not explain resource use. The results also reveal a
      more complex model in which, for instance, the concepts of medical task and
      medical professional work are not easy to separate. The results highlight the
      interest in conceptualizing and analysing medical practice in work groups. It
      raises important issues that have seldom been taken into account in the study of
      medical practice variations, which has tended to focus on attending physicians.

PMID- 11507812
TI  - Evaluating medical information systems: ethnomethodological and interactionist
      approaches.
AB  - This paper examines how qualitative research can contribute to the evaluation of
      medical information systems. Most qualitative studies of the use of medical
      computer systems adopt either an interactionist or, less commonly, an
      ethnomethodological perspective. The paper compares and contrasts the two
      approaches through the detailed discussion of two case studies, one rooted in
      each tradition. It identifies the implications of using these different
      analytical approaches and assesses their strengths and weaknessess. The paper
      argues that the preference for interactionism has led qualitative researchers to
      overlook important aspects of the social processess which surround the use of
      computer systems and that, consequently, a shift in emphasis towards
      ethnomethodological research is necessary. Nonetheless, it concludes by asserting
      that both strands of qualitative research can illuminate the organizational
      impact of medical computer systems.

PMID- 11507813
TI  - Impact of human resource management practices on nursing home performance.
AB  - Management scholars and practitioners alike have become increasingly interested
      in learning more about the ability of certain 'progressive' or 'high-performance'
      human resource management (HRM) practices to enhance organizational
      effectiveness. There is growing evidence to suggest that the contribution of
      various HRM practices to impact firm performance may be synergistic in effect yet
      contingent on a number of contextual factors, including workplace climate. A
      contingency theory perspective suggests that in order to be effective, HMR
      policies and practices must be consistent with other aspects of the organization,
      including its environment. This paper reports on empirical findings from research
      that examines the relationship between HRM practices, workplace climate and
      perceptions of organizational performance, in a large sample of Canadian nursing
      homes. Data from 283 nursing homes were collected by means of a mail survey that
      included questions on HRM practices, programmes, and policies, on human resource
      aspects of workplace climate, as well as a variety of indicators that include
      employee, customer/resident and facility measures of organizational performance.
      Results derived from ordered probit analysis suggest that nursing homes in our
      sample which had implemented more 'progressive' HRM practices and which reported
      a workplace climate that strongly values employee participation, empowerment and
      accountability tended to be perceived to generally perform better on a number of
      valued organizational outcomes. Nursing homes in our sample that performed best
      overall were found to be more likely to not only have implemented more of these
      HRM practices, but also to report having a workplace climate that reflects the
      seminal value that it places on its human resources. This finding is consistent
      with the conclusion that simply introducing HRM practices or programmes, in the
      absence of an appropriately supportive workplace climate, will be insufficient to
      attain optimal organizational performance.

PMID- 11507814
TI  - Comparing uninsured and privately insured hospital patients: admission severity,
      health outcomes and resource use.
AB  - This paper compares uninsured hospital patients with privately insured patients
      in terms of severity of illness on admission, emergency department use, leaving
      the hospital against medical advice, length of stay, and in-hospital mortality
      and morbidity rates. This cross-sectional study includes 29,237 admissions to 100
      US hospitals in 1993 and 1994. We found that uninsured patients are sicker,
      indicating that hospitals should expect uninsured patients to have increased
      service needs. Our results indicate that the uninsured exhibit higher likelihood
      of leaving against medical advice, shorter lengths of stay and poorer health
      outcomes suggest that the uninsured may not be receiving necessary care. Further
      studies are needed.

PMID- 11507815
TI  - Use 'customer service' approach with external case managers.

PMID- 11507816
TI  - Alternative case manager model improves outcomes.

PMID- 11507817
TI  - Hepatitis C: proven case management strategies.

PMID- 11507818
TI  - Learn more about your stakeholders via analysis.

PMID- 11507819
TI  - Follow new pediatric guidelines or risk liability.

PMID- 11507820
TI  - Inpatient and SDS: one unit or two?

PMID- 11507821
TI  - AHRQ sends mixed message on guidelines.

PMID- 11507822
TI  - The managed care cycle: taking control of your system's contracted business.

PMID- 11507823
TI  - Market is ripe for hospitals to define and determine their futures.

PMID- 11507824
TI  - Quality compensation incentives work when system fosters quality.

PMID- 11507825
TI  - Patients rights portends changes for hospitals.

PMID- 11507826
TI  - Selenium speciation in waters: role of dissolved polysaccharides on the
      mobilization process.
AB  - The paper deals with the study of selenium speciation in a water system where
      antropic contribution could be relevant (Tiber river). The speciation at natural
      levels was determined before, inside, after the city of Rome by a previously
      defined method: the tetravalent state is prevalent in the anthropized zone while
      the highest oxidation state is predominant outside. The study of the storage
      effects (on a whole sample) and the distribution (fate) of the selenium
      contribution were also carried out. The study showed how in polluted waters the
      fraction of dissolved organic matter able to bind Se(IV) highly affects the
      mobility of selenium in the matrix. Polysaccharide species show this property, so
      they are be very probably responsible for the adsorption of selenium on
      particulate and stabilize this form against oxidation.

PMID- 11507827
TI  - Improvements in the sample preparation for the determination of ruthenium in
      catalysts by different spectrometric techniques.
AB  - The sample preparation steps of two analytical methods for the determination of
      ruthenium in carbon supported catalysts with flame atomic absorption spectrometry
      (FAAS) or UV-vis spectrophotometry, were carefully optimised. As a first step,
      the carbon support is ignited in air at 450 degrees C then the residue is fused
      with potassium hydroxide and potassium nitrate to convert ruthenium into
      ruthenate anion RuO4(2-). The melt is dissolved in water with potassium
      persulphate and potassium hydroxide as stabilisers. Ruthenium may be directly
      estimated by measuring the UV-vis molecular absorption of ruthenate at the
      isosbestic point of the ruthenate-perruthenate mixture or by FAAS. In the latter
      case, an aliquot of the sample solution is added to the concentrated hydrochloric
      acid to obtain hexachlororuthenate RuCl6(2-), that is nebulized into the flame
      after proper dilution. This novel procedure allows to determination of ruthenium
      without the sensitivity loss (-66%) which occurs in the alkaline media resulting
      from the fusion. The relative standard deviation is 1.1% for FAAS and 1.3% for UV
      vis, at 5% Ru (n = 7). The detection limit (3sB) is 0.07% Ru for FAAS and 0.02%
      Ru for UV-vis. Both methods were applied to the analysis of a commercial sample
      and a statistical comparison was carried out.

PMID- 11507828
TI  - On the formation of iron(III) hydroxo acetate complexes.
AB  - The formation of hydroxo acetate complexes of iron (III) ion has been studied at
      25 degrees C in 3 M (Na)ClO4 ionic medium by measuring with a glass electrode the
      hydrogen ion concentration in Fe(ClO4)3-HClO4-NaAc mixtures (Ac = acetate ion).
      The acetate/metal ratio ranged from 0 to 6, the metal concentration varied from
      0.005 to 0.06 M, whereas [H+] was stepwise decreased from 0.1 M to initial
      precipitation of hydroxo-acetates. This occurred, depending on the acetate/metal
      ratio, in the -log[H+] range 1.85-2.7. The potentiometric data are consistent
      with the presence of Fe3(OH)3Ac3(3+), Fe2(OH)2(4+), Fe3(OH)4(5+), Fe3(OH)5(4+)
      and, as minor species, of Fe3(OH)2Ac6+, FeAc2+, FeAc2+, FeOH2+ and Fe(OH)2+.
      Previously published EMF measurements with redox and glass half-cells were
      recalculated to refine the stability constants of FeAc2+, FeAc2+ and
      Fe3(OH)2Ac6+. Formation constants *beta pqr for pFe(3+)+(q-r)H2O + rHAc
      reversible Fep(OH)(q-r)(Ac)r3p-q + qH+ (in parenthesis the infinite dilution
      value): log*beta 111 = -1.85 +/- 0.02 (-0.67 +/- 0.15), log*beta 122 = -3.43 +/-
      0.02 (-1.45 +/- 0.15); log*beta 363 = -5.66 +/- 0.03 (-2.85 +/- 0.40), log*beta
      386 = -8.016 +/- 0.006 (-4.06 +/- 0.15), log*beta 220 = -2.88 +/- 0.02 (-2.84 +/-
      0.05), log*beta 340 = -6.14 +/- 0.18 (-6.9 +/- 0.4), log*beta 350 = -8.44 +/-
      0.09 (-7.65 +/- 0.15).

PMID- 11507829
TI  - Rapid determination of tannins in tanning baths by adaptation of BSA method.
AB  - A rapid and reproducible method for the determination of tannins in vegetable
      tanning baths is proposed as a modification of the BSA method for grain tannins
      existing in literature. The protein BSA was used instead of leather powder
      employed in the Filter Method, which is adopted in Italy and various others
      countries of Central Europe. In this rapid method the tannin contents is
      determined by means a spectrophotometric reading and not by means a gravimetric
      analysis of the Filter Method. The BSA method, which belongs to mixed methods
      (which use both precipitation and complexation of tannins), consists of selective
      precipitation of tannin from a solution containing also non tannins by BSA, the
      dissolution of precipitate and the quantification of free tannin amount by its
      complexation with Fe(III) in hydrochloric solutions. The absorbance values, read
      at 522 nm, have been expressed in terms of tannic acid concentration by using a
      calibration curve made with standard solutions of tannic acid; these have been
      correlated with the results obtained by using the Filter Method.

PMID- 11507830
TI  - Metal and non-metal micro-pollutants in cultivated soils of Lecce and Brindisi
      districts (Apulia, southern Italy).
AB  - To estimate the presence of metal and non-metal micro-pollutants in the soils of
      the Lecce and Brindisi districts, an analytical study has been carried out on
      samples of surface soils taken from agricultural areas. The research has
      concerned the determination of the following micro-pollutants: Cu, Ni, Cr, Zn,
      Pb, Be, Cd, As, Hg, Sb e Tl. Statistical techniques, such as Principal Component
      Analysis and Clustering Analysis, have been utilised to examine the correlations
      among the different parameters and to define contamination areas. The results
      show that the amount of micro-pollutants in the superficial stratum of the
      examined soils is in the range permitted by the regulations in force, with the
      exception of arsenic and thallium. Arsenic concentrations are near to the maximum
      admissible value, while thallium concentrations are in 56% of the samples higher
      than the admissible value both in the soil and underground. The most significant
      parameter from a toxicological point of view is thallium, which has its maximum
      concentration in the soils located near the industrial area of Brindisi.

PMID- 11507831
TI  - Accurate quantitative measurements of asbestos in XRPD analysis.
AB  - X-ray Powder Diffraction (XRPD) quantitative analysis of fibrous substances like
      asbestos, is strongly influenced by systematic errors due to preferred
      orientation, as a consequence of their morphology. In the present work we have
      compared the accuracy of quantitative measurements performed by using the
      Internal Standard (IS) method and the Reference Intensity Ratio (RIR) method in
      the analysis of the same diffractographs. Both these analytical methods are based
      on the same principle but the data analysis procedures are different. We have
      particularly studied how, in the RIR case, the evaluation of several diffraction
      lines of both phases, standard and unknown, increases the accuracy of a
      quantitative determination, balancing the different effect due to systematic
      errors on the measurements of distinct peaks.

PMID- 11507832
TI  - A potentiometric study on oxalate and citrate complexes of tin(II).
AB  - The formation of oxalate and citrate complexes of the Sn2+ ion in 1 M Na(ClO4) at
      25 degrees C was investigated in the -log[H+] range 2 to 5 by potentiometric
      titrations using glass and tin amalgam electrodes. The tin concentration was
      varied from 0.5 to 5 mM and the concentration of the ligands from 1 to 40 mM. The
      experimental data have been explained by the formation of the oxalato complexes
      SnC2O4(aq) and Sn(C2O4)2(2-) and of the citrate complexes (C3H5O7(3-) = citrate
      ion) SnC3H5O7-, SnHC3H5O7(aq), SnH2C3H5O7+ and Sn(OH)C3H5O7(2-). The equilibrium
      constants were refined by the computer program SUPERQUAD. The final values of the
      constants on the medium scale and in the infinite dilution reference state are
      given in Table 2.

PMID- 11507833
TI  - Role played by a natural channel on the quality of bordering environment: a
      chemical assessment.
AB  - Based on a rational and simple chemical approach, a field-investigation aimed to
      assess the role played by a natural channel "lama" on the quality of underlying
      groundwater and neighbouring soils has been carried out. The results have
      demonstrated that: (a) the stream flowing through the "lama" is mainly made up of
      treated effluent from a nearby municipal wastewater treatment plant; (b) the
      occurrence of nitrates in the "lama" is due to rain-washing of nitrogen
      fertilized agricultural soils bordering on the "lama"; (c) hydraulic connections
      exist between the lama and the underlying groundwater causing contaminants
      flowing through the "lama" to reach groundwater within less than one week; (d)
      compared with the values measured in the "lama", the concentrations of TOC, N-NH4
      and N-NO3 in groundwater result: lower, far lower and greater, respectively; (e)
      agricultural soils bordering on the "lama" result significantly contaminated by
      halogenated organics.

PMID- 11507834
TI  - N,N-diethyl-N'-benzoylthiourea--a new spectrophotometric reagent for rhenium
      determination.
AB  - The reagent N,N-diethyl-N'-benzoylthiourea produces a green complex with rhenium
      in hydrochloric acid medium in the presence of tin(II) chloride. The complex
      extracted into toluene shows an absorption maximum at 383 nm, obeys Beer's law
      from 1.5 to 22 micrograms ml-1 of rhenium while its molar absorptivity and
      Sandell sensitivity are 6.66 x 10(3) L mol-1 cm-1 and 0.028 microgram cm-2,
      respectively. It tolerates the presence of a large number of ions, including
      Mo(VI), W(VI) and some platinum metals. Job's and the mole ratio methods indicate
      that the rhenium metal and the chelating agent ratio of 1:2 in solution. The
      system has been applied to the determination of rhenium on synthetic samples and
      alumina based catalysts.

PMID- 11507835
TI  - The stability constants of the rare earth complexes with trimetaphosphoric acid.
AB  - The stability constants of the complexes formed between the rare earth metal ions
      and the anion of trimetaphosphoric acid have been determined at a temperature of
      20 degrees C and an ionic strength of mu = 0.1 by the ion-exchange equilibrium
      method. The investigations indicate that stabilities of complexes increased from
      La to Lu. The highest and the lowest stability constant values (beta) were found
      to be 7.76 and 3.82 for Lu3+ and La3+ respectively.

PMID- 11507836
TI  - Column preconcentration of trace manganese with the ion pair of 2-nitroso-1
      naphthol-4-sulfonic acid tetradecyldimethylbenzyl-ammonium chloride supported on
      naphthalene and determination by derivative spectrophotometry.
AB  - A column preconcentration method has been developed for the determination of
      trace amounts of manganese by preconcentration on 2-nitroso-1-naphthol-4-sulfonic
      acid (nitroso-S)-tetradecyldimethylbenzylammonium (TDBA) naphthalene as an
      adsorbent using a simple funnel tipped glass tube. Manganese reacts with nitroso
      S to form a water soluble brown colored chelate anion. The chelate anion forms a
      water insoluble Mn-Nitroso-S-TDBA ion pair on naphthalene packed in a column in
      the pH range 9.6-10.5 at a flow rate of 1-2 ml/min. The solid mass consisting of
      manganese complex and naphthalene is dissolved in 5 ml of dimethylformamide (DMF)
      and the metal determined by second derivative spectrophotometry. The calibration
      curve is linear in the concentration range 0.25-35.0 micrograms of Mn in 5 ml of
      the final DMF solution. Eight replicate determinations of 25 micrograms of
      standard manganese solution give a mean peak height of 4.0 with a correlation
      coefficient of 0.9995 and relative standard deviation of +/- 1.1%. The
      sensitivity was calculated to be 0.502(d2 A/d lambda 2)/microgram ml-1 from the
      slope of the calibration curve. The detection limit was 0.020 microgram ml-1 for
      manganese at the minimum instrumental settings (signal to noise ratio = 2).
      Various parameters effecting the method such as the effect of pH, volume of
      aqueous phase and interference of a number of metal ions on the determination of
      manganese have been evaluated to optimize the conditions for its determination in
      standard alloys and biological samples.

PMID- 11507837
TI  - Effect of perchlorate ion within the polypyrrole matrix on the electrooxidation
      of ethylene glycol in acidic media.
AB  - The electrooxidation of ethylene glycol was investigated on platinum and
      perchlorate ions doped polypyroole film electrodes in acidic media. The presence
      of perchlorate ion was observed by XPS experiments. Optimum experimental
      conditions were determined. The electrooxidation kinetic of ethylene glycol was
      studied as a function of ethylene glycol concentration, potential scan limit and
      scan rate. Results suggest that the doping process has a strong effect on the
      oxidation reaction.

PMID- 11507838
TI  - Corrosion of Cu-xZn alloys in slightly alkaline chloride solutions studied by
      stripping voltammetry and microanalysis.
AB  - The mechanism of corrosion of Cu-xZn alloys (x = 10-40 wt %) in slightly alkaline
      chloride solutions was investigated by analysing solid reaction products by
      energy dispersive X-ray analysis (EDS) and dissolved reaction products by
      differential anodic pulse stripping (DAPS) voltammetry. The corrosion process was
      studied under open circuit and under potentiostatic conditions at selected
      potentials. Pure metals were studied comparatively so that an interacting effect
      of particular metal components in the alloy could be determined. All four Cu-xZn
      alloys show an improved behaviour compared to pure metals. Under open-circuit
      condition both components dissolve simultaneously in the solution. With
      increasing immersion time the preferential, dissolution of zinc in the solution
      becomes pronounced. It is the highest for Cu-10Zn and the lowest for Cu-30Zn
      alloy. Under potentiostatic control the dissolution mechanism depends on the
      electrode potential and changes from exclusive dissolution of zinc to
      simultaneous dissolution of both components with preferential dissolution of
      zinc. The latter decreases, as the electrode potential becomes more positive.

PMID- 11507839
TI  - Determination of the thermodynamic parameters and stability constants of UO2(2+),
      Th4+, and Ce3+ complexes with some azo-benzene-N-malonic acid derivatives.
AB  - Proton-ligand dissociation and metal-ligand formation constants of azobenzene-N
      malonic acid (I), p-Cl-azobenzene-N-malonic acid (II), p-Br-azobenzene-N-malonic
      acid (III) and p-COOH- azobenzene-N-malonic acid (IV) with UO2(2+), Th4+ and Ce3+
      were evaluated potentiometrically using Bjerrum's method at 25, 35 and 45 +/- 0.5
      degrees C and ionic strength 0.1 M in 40% v/v ethanol-water medium. The order of
      stability constants was found to be Ce3+ > Th4+ > UO2(2+). The effect of
      temperature on the dissociation and stability constants of the formed complexes
      was studied and the corresponding thermodynamic functions were derived and
      discussed. The ratio of metal-ligand was determined conductometrically. The
      structure of the ligands under investigation as well as their metal complexes has
      been elucidated by elemental analysis, IR and 1HNMR spectroscopy.

PMID- 11507840
TI  - A new rapid method for measurement of nitrogen.

PMID- 11507841
TI  - Trace metals in marine bivalve molluscs sampled near the Italian base in
      Antarctica.

PMID- 11507842
TI  - Water and acetic acid leachable Cd, Cr, Cu, Fe, Ni, Pb and Zn in lime-treated
      sewage sludge.

PMID- 11507843
TI  - Comments to the paper "Assessment of the metal contamination of the low Sebou
      sediments": Ann. Chim. (Rome), 91, 637-644 (2000).

PMID- 11507844
TI  - Malocclusions and traumatic injuries in disabled schoolchildren and adolescents
      in Kuwait.
AB  - The present study was carried out to determine the prevalence of malocclusion and
      traumatic injuries in disabled children and adolescents attending the special
      needs schools in Kuwait. Included in the study were 818 children (438 males and
      380 females), in the age groups of 3-20 years, who have visual impairment,
      hearing impairment, physical handicaps, or developmental disorders. The mean age
      of participants was 11.9 years. The survey was carried out according to the
      methods of WHO. The prevalence of severe malocclusion was 23.6%, and that of
      slight malocclusion was 37.0%. Children with Down syndrome (OR = 2.3; 95% CI =
      1.51-3.52), those of increasing age (OR = 1.1; 95% CI = 1.01-1.10), and males (OR
      = 1.5; 95% CI = 1.05-2.07) had higher risk for the occurrence of severe
      malocclusion. Less than one-fifth of the subjects (16.9%) had traumatized
      anterior teeth. Severe malocclusion (OR = 1.8; 95% CI = 1.17-2.77) and increasing
      age (OR = 1.2; 95% CI = 1.13-1.26) were significant risk factors for the
      occurrence of traumatic injuries. We concluded that malocclusion and traumatic
      injuries are more prevalent among these subjects with disabilities than among the
      healthy population in Kuwait.

PMID- 11507845
TI  - Managing patients on warfarin therapy: a case report.
AB  - Coagulotherapy is a common therapeutic regimen most frequently utilizing
      warfarin. This therapy may have important dental ramifications. An understanding
      of the mechanisms of action and drug interactions may help avoid problems.
      Questions commonly arise as to what dental procedures may be safely considered
      when a patient is on anticoagulant therapy. The coagutherapy level is measured in
      values of the International Normalized Ratio (INR). Any question about the
      appropriateness of dental procedures should be referred to the physician
      prescriber of the anticoagulant therapy. Generally, controlling bleeding is less
      of a problem than the management of thrombi and vascular occlusion from decreased
      coagutherapy. A case is presented in which the INR reached a critical value as
      the result of drug interactions and miscommunication.

PMID- 11507846
TI  - Attitudes of dentists, working in Riyadh, toward people with a sensory
      impairment.
AB  - This study was conducted to determine the attitudes of dentists, working in
      Riyadh, toward people with a sensory impairment (SI), according to the Scale of
      Attitude Towards Disabled Persons (SADP). The SADP scale was modified to focus
      solely upon sensory impairment. The modified scale was pre-tested and then
      incorporated into a self-administered questionnaire. This was then administered
      to 600 dentists (response rate, 73.7%) working in the city of Riyadh, Saudi
      Arabia. The modified scale showed itself to be reliable, with a Chronbach's
      coefficient alpha 0.616 and four-factor analysis, which accounted for 38.5% of
      the variance. Ninety-four percent of the dentists were generally positive toward
      SI in the society. There were, however, significant variations in attitudes, with
      a more positive score for dentists who had worked for 30 years or more (p <
      0.005), were specialists (p < 0.005), received little or no undergraduate
      training in this subject (p < 0.05), and who received their undergraduate
      training in Europe/North America (p < 0.001). However, in a stepwise regression
      model, all these variables were significant except for the years of practice. The
      modified SADP showed dentists, working in Saudi Arabia, having a positive
      attitude toward people with SI.

PMID- 11507847
TI  - Oral health is not an isolated dental problem.

PMID- 11507848
TI  - The Surgeon General's Report and special-needs patients: a framework for action
      for children and their caregivers.
AB  - The Surgeon General's Report, Oral Health in America, is the first comprehensive
      assessment of oral, dental, and craniofacial health in the history of our nation.
      The intent of this first-ever Report is to alert Americans to the full meaning of
      oral health and its importance to general health and well-being across the
      lifespan. Moreover, the Report has been released at a time in human history of
      enormous changes as well as opportunities. The convergence of public health
      policies, "quality of life" expectations, global informatics, a new century of
      biotechnology, the completion of the Human Genome Project, changes in the
      management of health care, and the acknowledgment of enormous health disparities
      herald a call to action. These profound dynamics particularly affect children and
      their caregivers and the multitude of social, economic, and health issues
      associated with special patients and developmental disabilities. This paper will
      highlight the issues, provide recommendations, and suggest a call to action.

PMID- 11507849
TI  - Today's dental student is training for tomorrow's elderly baby boomer.
AB  - We are constantly reminded of the exploding elderly population and the increasing
      demand to meet their needs. But do we fully understand and appreciate the impact
      that this fastest-growing segment of the population will have upon our
      profession? Whether we realize it or not, today's dental student is training for
      tomorrow's elderly baby boomer. The baby boomer generation is 76 million strong,
      representing 19 years worth of births spanning from 1946-1964. That makes the
      oldest baby boomer 55 years old and the youngest 37 years old. What does this all
      mean? That from 2011-2030, the age group of 65 years of age and older will make
      up approximately 22% of the population, vastly changing our patient population,
      not to mention a significant increase in patient load. The future holds promise
      for not only a busy career, but also potentially a financially rewarding one as
      well. To some extent, we are all going to be geriatric clinicians. There is
      little doubt that there will be a great demand for services in restorative
      dentistry, prosthodontic dentistry, endodontics, periodontics, oral surgery, and
      perhaps orthodontics. As the baby boomers benefited from fluoride and sanitation,
      more people have been able to maintain their dentition and health into their
      older years. Dental students graduating today will be only beginning the prime of
      their careers as the baby boomers make their introduction in full force in the
      year 2011.

PMID- 11507851
TI  - Two thumbs down. Focus groups react negatively to AHA's workforce crisis pitch.

PMID- 11507850
TI  - Periodontal health status and treatment needs among the elderly.
AB  - The numbers of dentate elderly are growing rapidly in all industrialized
      countries, and epidemiological information about their oral health is urgently
      needed. Our study is part of the population-based Helsinki Ageing Study (HAS),
      and this paper describes the periodontal health status as well as the need for
      periodontal treatment among the dentate elderly born in 1904, 1909, and 1914 and
      living in January, 1989, in Helsinki, Finland (n = 175). The dental examinations
      were carried out during 1990 and 1991 at the Institute of Dentistry, University
      of Helsinki, Finland. The subjects' periodontal health was recorded by the CPITN
      (Community Periodontal Index of Treatment Needs) method. The mean number of
      remaining teeth was 15.1 among men and 14.0 among women, with the mean number of
      remaining sextants 3.7 and 3.5, respectively. Healthy periodontal tissues (CPI =
      0) were found in 7% of the subjects. Bleeding on probing (CPI = 1) was recorded
      in 6%, and calculus and/or overhanging margins of restorations (CPI = 2) in 41%
      of the subjects, as the worst finding. Altogether, 46% of the subjects had deep
      periodontal pockets, 35% with at least one 4- to 5-mm pocket (CPI = 3), and 11%
      with at least one > or = 6-mm pocket (CPI = 4). Overall, 93% of the subjects
      required oral hygiene instruction, 87% scaling and root planing, and 11% complex
      periodontal treatment. The periodontal treatment need was significantly higher in
      men than in women; however, no significant differences were observed among the
      three age cohorts. The need for complex periodontal treatment was unexpectedly
      low, probably explained by the fact that there were many missing teeth,
      especially molars, perhaps lost due to poor periodontal health.

PMID- 11507852
TI  - A bundle, then a flip-flop. N.J. hospitals gain substantially as state's
      lawmakers support Bush plan.

PMID- 11507853
TI  - AHERF scandal widens. Three outside auditors charged with securities fraud in SEC
      civil lawsuit.

PMID- 11507854
TI  - Keeping the focus. UVA decides to sell money-losing 'distraction,' to Coventry.

PMID- 11507855
TI  - DMC backs out of OmniCare deal. Turnaround unlikely as 97,000-member HMO put
      under state control.

PMID- 11507856
TI  - 'Time to begin an orderly transition'. With HCA's turnaround well under way,
      Frist stepping down as chairman.

PMID- 11507857
TI  - Desert lasis. Chain may try to sell beleaguered Phoenix-area hospitals, sources
      say.

PMID- 11507858
TI  - There's no place like home. No Texas deal for Menninger, but clinic still
      looking.

PMID- 11507859
TI  - Paying the piper. California hospitals brace for mandatory compliance costs.

PMID- 11507860
TI  - Not so golden now. Calif. hospitals scramble to keep energy use low as rate hikes
      bite hard.

PMID- 11507861
TI  - Ugly wait at the counter. Insurer pushes to make allergy drugs nonprescription.

PMID- 11507862
TI  - Help, with strings. Hospitals may find Congress will attach some controls to
      funding for new nurses.

PMID- 11507863
TI  - No boundaries. Texas' Christus Health bucks trend by looking to Mexico for
      expansion.
AB  - Christus Health has bucked the trend by looking to Mexico for expansion. The
      Roman Catholic system based in Irving, Texas, bought 51% of Hospital Muquerza in
      the prosperous northern Mexico state of Nuevo Leon. Christus believes the move
      makes sense on many levels.

PMID- 11507864
TI  - Marginally better off. Survey shows more systems post a profit, but for many it's
      barely break-even.

PMID- 11507865
TI  - Contract management. Consultants, software help maximize payments.

PMID- 11507866
TI  - Accepting responsibility. Two hospitals admit central roles in recent deaths.

PMID- 11507867
TI  - AHA announces new safety award.

PMID- 11507868
TI  - Sin of omission? Pharmaceutical trade group failed to disclose that ad subject
      was employee.

PMID- 11507870
TI  - Don't let the bugs bite.

PMID- 11507871
TI  - Consultant appraisal. Getting won over.

PMID- 11507872
TI  - Open space. Pounds, shillings and sense.

PMID- 11507873
TI  - Joint working. Stories in the making.
AB  - Joint working is likely to increase. But it does not necessarily improve
      efficiency. The essential change required is cultural, not structural.

PMID- 11507874
TI  - Telegraph route.

PMID- 11507875
TI  - [Scanning electron microscopy of peripheral blood erythrocytes in the diagnosis
      and treatment of hemorrhagic vasculitis in children].
AB  - Twenty-four children aged 3-15 years were examined, 16 of these with cutaneous
      and articulo-cutaneous hemorrhagic vasculitis (HV) and 8 normal controls. The
      patients were divided into 2 groups: 10 patients treated by basic therapy and 6
      children whose treatment protocols were supplemented by membranoprotector
      locheine. The children were repeatedly examined 1 month after discharge from
      hospital. Scanning electron microscopy of peripheral blood erythrocytes provides
      valuable diagnostic data on erythrocyte membrane morphology and function in
      children with HV and can serve as a method for monitoring the efficiency of new
      approaches to therapy of this disease.

PMID- 11507876
TI  - [Analysis of changes in erythrocyte thermoresistance in lung cancer].
AB  - Heat-induced hemolysis of erythrocytes was evaluated by the equilibrium method at
      54-60 degrees C in patients with lung cancer and donors. Thermal sensitivity of
      patients differed from that of normal subjects and the seeming energy of
      erythrocyte lysis activation was lower in patients (230 kJ/mol) than in the
      controls (345 kJ/mol). Presumably changed structural characteristics of membrane
      bilayer affected the physicochemical properties of erythrocytes, determining,
      among other things, thermal resistance of red blood cells.

PMID- 11507877
TI  - [Spontaneous migration of blood neutrophils in mixed leukocyte population and its
      changes under the effect of auto-plasma substances in various functional states].
AB  - Modified method for studies of leukocyte migration under agarose allows
      evaluating the spontaneous locomotion activity of cells and its changes under the
      effects of humoral factors accumulating in the blood in various pathological and
      extreme states. Trials of the method confirmed the possibility of its use for
      evaluation of locomotion changes depending on cell functions and mediated by
      plasma factors in various conditions.

PMID- 11507878
TI  - [Fluorescent evaluation of blood nuclear cells in experimental myocardial
      infarction].
AB  - Functional (synthetic) activity of acridine orange-stained blood nuclear cells
      was studied by microspectral fluorescent analysis in experimental myocardial
      infarction. A specific time course of changes in the synthetic activity of blood
      nuclears, described by alpha parameter, was detected in uneventful myocardial
      infarction and infarction complicated by suppurative inflammation of the suture.
      This time course reflected the reparative changes in the myocardium. Hence, alpha
      parameter can be regarded as an indicator of reparative processes in the
      myocardium, and the above method recommended for fluorescent cytodiagnosis of
      reparation processes after acute myocardial infarction and for predicting its
      course.

PMID- 11507879
TI  - [Significance of blood ribose measurement by gas liquid chromatography in
      ischemic hear disease].
AB  - A method for measuring serum ribose by gas liquid chromatography is described,
      prolonging the sample stability and simplifying its storage. Serum ribose content
      is decreased in patients with angina of effort (functional class III).

PMID- 11507880
TI  - [Biorheology. Clinical hemorheology. Fundamental notions, parameters, equipment].

PMID- 11507881
TI  - [Morphofunctional characteristics of erythron (review of the literature)].

PMID- 11507882
TI  - [Measurement of plasma renin activity using fluorescent substrate renin].
AB  - Direct chromatographic method for measuring renin activity by high-performance
      liquid chromatography has been developed. The method is based on enzymatic
      hydrolysis of a new fluorescent substrate renin with formation of fluorescent
      angiotensin I (fAI). The content of fAI is evaluated by a calibration curve
      reflecting a linear relationship between the ratio of fAI and internal standard
      areas and the amount of resultant fA1 in reaction mixture. 100 microliters plasma
      is needed for analysis. After 1-h incubation at 37 degrees C the reaction mixture
      is introduced directly into chromatographic system with a precolumn. Acetonitrile
      gradient in 0.05 M Tris-TPU buffer (pH 8.0) allows a satisfactory separation of
      hydrolysis products. The sensitivity of the method is 100 pg fAI/ml. The method
      adequately reflects species characteristics of plasma renin activity and its
      changes caused by stimulation of renin secretion, is characterized by higher
      selective activity than radioimmunoassay, and is more rapid.

PMID- 11507883
TI  - [Measurement of blood homocysteine by high performance liquid chromatography
      (HPLC)].
AB  - Hyperhomocysteinemia is an independent risk factor for atherosclerosis and
      vascular occlusive diseases. Measurements of total homocysteine (Hcy) require an
      accurate reproducible method. A high-performance liquid chromatographic (HPCL)
      method for evaluating plasma Hcy after reduction with 2-mercaptoethanol and
      precolumn derivatization with iodoacetic acid and o-phthaldialdehyde is
      described. The resultant derivatives were separated on reverse-phase column C18
      in the isocratic HPCL mode with fluorimetric detection. The detection limit for
      Hcy is 0.8 mumol/liter. The concentration of Hcy after overnight fasting was
      increased significantly (p < 0.02) in the patients in comparison with the control
      (11.7 +/- 1.1 vs. 8.3 +/- 0.5 mumol/liter). The method can be used for measuring
      the concentrations of asparaginic acid, glutamic acid, cysteine, asparagine,
      serine, and glutamine.

PMID- 11507884
TI  - [Early evaluation of blood loss by the profile of blood proteins in patients with
      injuries].
AB  - The concentrations of positive (C-reactive protein, orosomucoid, haptoglobin,
      ceruloplasmin) and negative (transtiretine, alpha 2-macroglobulin, transferrin)
      markers of acute phase response were measured in 55 victims with injuries to
      hollow organs on day 1 of hospitalization. By visual intraoperative evaluation of
      blood loss, the patients were divided in 2 groups: with blood loss under 1 liter
      (n = 32, group 1) and more than 1 liter (n = 23, group 2). Acute phase response
      was more manifest in group 1. Blood loss affected the levels of orosomucoid and
      haptoglobin, which is explained by functional characteristics of these blood
      proteins. Orosomucoid and haptoglobin tests were highly sensitive, specific, and
      accurate in evaluation of blood loss in patients with hollow organ wounds (87.5,
      90, 89% and 80, 80, 80%, respectively). The content of these proteins equal to no
      more than 1 g/liter during the first day after the injury indicates blood loss
      higher than 1 liter with high probability.

PMID- 11507885
TI  - [Changes in the activities of oxidoreductases, content of malondialdehyde and
      medium weight molecules in the blood of patients with craniocerebral injuries of
      different severity].
AB  - Biochemical changes are determined by the severity of craniocerebral injury.
      Twenty-four hours after the injury the activity of succinate dehydrogenase in
      lymphocytes increases significantly in patients with brain concussion and
      contusion of medium severity. Glutamate dehydrogenase activity increases in
      patients with repeated brain concussion. The content of malonic dialdehyde is
      increased in patients with repeated brain concussion and decreased in severe
      brain contusion. The level of medium-weight molecules is increased in all
      patients with craniocerebral injuries. The activities of these enzymes are
      virtually unchanged in the patients with lethal outcomes.

PMID- 11507886
TI  - [Energy metabolism, free radical and microsomal oxidation and electrolyte
      metabolism in workers of oil processing industry].
AB  - Disorders in erythrocyte energy metabolism, plasma and erythrocyte electrolyte
      metabolism, erythrocyte, plasma, and urinary free-radical oxidation, and in the
      urinary microsomal monoxigenase system were detected in workers engaged in oil
      processing industry. All examinees were divided into 3 groups with different
      intensity of exposure to chemical pollutants: 1) workers having no contacts with
      chemicals (n = 21); 2) workers exposed to chemicals 2-3 times a week (n = 28,
      risk group); and 3) workers permanently exposed to chemicals for 3-5 years (n =
      45). Control group consisted of 40 subjects occupationally not exposed to
      chemicals. The findings indicate marked changes in energy metabolism, free
      radical and microsomal oxidation, and electrolyte metabolism in group 2 and more
      so in group 3.

PMID- 11507887
TI  - [Formation of a universal technological process of laboratory analysis.
      Experience gained at the Medical Center of the Central Bank of the Russian
      Federation].

PMID- 11507888
TI  - [Everyday quality control at clinical-biochemical laboratories using chi square
      test].
AB  - The possibility of using chi 2 statistical test for quality control of laboratory
      studies was evaluated in a practical laboratory. In the overwhelming majority of
      cases the chi 2 test of analytical series, estimated from previous results or
      total sum of results of a month, indicates with certainty that this series is a
      random sampling. This unambiguously indicates analytical reliability of the
      results. Division of patients into inpatients and outpatients did not improve
      this parameter. The results were regularly much better for some analytical
      methods in comparison with other methods, which indicates their higher
      reliability.

PMID- 11507889
TI  - [Hematological parameters in characterization of anemia in leptospirosis].
AB  - Blood samples from 46 patients with leptospirosis were analyzed on a Cobas Vega
      (ABX, France) device over the course of disease. Hemoglobin content, erythrocyte
      count, mean volume of erythrocytes, mean content and mean concentration of
      hemoglobin in an erythrocyte, anisocytosis index, reticulocyte count, and content
      of free hemoglobin (FH) were analyzed. Anemia (normocytic normochromic
      hyperregeneratory) is a typical manifestation of leptospirosis during the second
      week of disease. The leading pathogenetic mechanism of anemia associated with
      leptospirosis is erythrocyte hemolysis, whose intensity during the acute period
      depends on the severity of intoxication and extracorporeal methods of
      detoxication. Persistence of anemia during convalescent period is due to
      involvement of the kidneys (nephrotic nephritis).

PMID- 11507890
TI  - [Continuous measurement of baseline atmospheric carbon monoxide in western
      China].
AB  - In-situ custom-designed gas chromatography(GC)-HgO system was established for the
      continuous measurement of atmospheric CO at Waliguan Baseline Station(36 degrees
      17' N, 100 degrees 54' E, 3816 m asl) in western China. The system's assembling,
      testing, running and calibration indicated that the chromatographic method has
      stable baseline and high separation efficiency, as well as reliable detection
      method. This system adopted high automatic operating techniques and followed
      strict quality control. It is up to the standard of WMO's baseline watch on
      global atmosphere. According to the flask sampling results of in-situ CO
      variation at Waliguan, CO standards in clean dry air under international
      comparison were used to determine the adjustable working standard curves, so as
      to calculate the ambient CO mixing ratios based on peak height. This system's
      detection limit for CO is around 1 x 10(-9) (V/V), the precision is below 0.1%
      and accuracy in +/- 0.05%, it can provide continuous and accurate surface CO
      mixing ratios in baseline areas of China.

PMID- 11507891
TI  - [Retention of selenium volatility using lime in coal combustion].
AB  - For understanding the volatility of selenium, the effect of the contents of
      exchangeable cations of coal on it, and the retention of selenium using CaO in
      coal combustion, the sequential chemistry extraction, the fixed bed and
      circulating fluidized bed (CFB) combustion, X-ray diffraction (XRD) and atomic
      fluorescence spectrometry (AFS) were undertaken. The results showed that the
      volatility of selenium was more than 97% in coal combustion at 815 degrees C, and
      the volatility of selenium was affected by the content of exchangeable cations of
      coal in low-middle temperature. It was identified that lime can restrain the
      volatility of selenium. In fixed bed combustion of coal, the retention rates of
      selenium volatility were between 11.6% and 50.7% using lime. In circulating
      fluidized bed combustion of coal, partitioning of selenium changed very much in
      ash of different size fraction between without lime and with lime. Comparing with
      combustion without lime, the content of selenium in ash from chimney was less
      than fourth times and that in leaching water from chimney decreased by two orders
      of magnitude using lime. Retention of selenium volatility using lime is so
      effective in coal combustion, especially in CFB combustion of coal.

PMID- 11507892
TI  - [Wet FGD process on rotating-stream-tray tower with magnesium-enhanced lime].
AB  - Wet flue gas desulfurization(FGD) process with magnesium-enhanced lime slurry was
      conducted on a rotating-stream-tray tower. Changes of SO2 removal efficiency and
      slurry pH with time were experimentally determined. Effects of magnesium sulfate
      concentration were investigated and the lime utilization was calculated according
      to experimental data. In comparison with lime FGD process, adding magnesium
      sulfate could effectively enhance SO2 removal efficiency; when the adequate
      magnesium sulfate concentration was 0.2 mol/L, the removal efficiency was more
      than 60% with two rotating-stream-trays, while the removal efficiency of lime
      process was only 45%. To achieve higher SO2 removal efficiency, the slurry pH
      should be controlled between 6.0 and 7.5. Magnesium sulfate could also promote
      lime dissolution, slow down descent of slurry pH and increase lime utilization;
      when magnesium sulfate concentration was 0.2 mol/L, lime utilization could be
      increased by more than 5 percentage point under adequate conditions.

PMID- 11507893
TI  - [The granulation of PCP-degrading anaerobic sludge with industrial organic
      wastewater as co-substrate].
AB  - The granulation of PCP degrading anaerobic sludge in two improved UASB reactors
      under co-existence of two types of industrial wastewater and PCP were studied. It
      was found that the granulation of PCP degrading anaerobic sludge could be divided
      into three stages, i.e. sludge acclimation, granular pre-formation and granular
      maturation. The changes in biomass, sludge bioactivity, population and ecological
      distribution of three group bacteria involved in anaerobic digestion during the
      course of granulation were also examined. Anaerobic granules from two reactors
      showed high dechlorination activity at meta, otho and para position. Rod-shaped
      and filamentous shaped Methanosaeta-like spp. were found in anaerobic granules.
      Results of electron microscopy revealed the presence of synthophic microcolonies
      and non-layed microstructure in PCP-degrading granules. The types of industrial
      wastewater used as co-substrate had affected the course of sludge granulation,
      dechlorinating activity and pre-dominant methanogens in PCP-degrading anaerobic
      granules.

PMID- 11507894
TI  - [Degradation of trichloroethylene by discharge plasma process].
AB  - Two types of discharge and two kinds of discharge reactors was employed to
      decompose trichloroethylene (TCE) in air. The results showed that both pulsed
      discharge and AC discharge were efficient to the degradation of TCE. Under the
      pulsed discharge with peak voltage of 42 kV, gas resident time of 15 s and TCE
      initial concentration of 1350 mg/m3, the degradation efficiency of TCE was close
      to 100% in the hallow reactor and the higher voltage results in a higher
      degradation efficiency. For the AC discharge, the degradation efficiency of TCE
      reached 90% with applied voltage of 30 kV. Meanwhile, increasing the applied
      frequency of AC voltage can enhance the degradation of TCE. The energy
      consumption for TCE degradation by AC discharge was higher than that by pulsed
      discharge. The energy consumption for TCE degradation efficiency of 80% by pulsed
      and AC discharge were 4.9 W.h/m3 and 116 W.h/m3, respectively. In addition, the
      energy consumption in the packed reactor was higher comparing with that in the
      hallow one.

PMID- 11507895
TI  - [Acid producing potential of a lead/zinc mine tailings at Lechang, Guangdong
      Province].
AB  - The acid producing potential of a Pb/Zn mine tailings at Lechang City, Guangdong
      Province were studied using both net acid generation (NAG) and net acid
      production potential (NAPP) methods. The pyritic and total sulfur contents of the
      tailings were 12.57% and 18.68% respectively. The NAG and NAPP values were H2SO4
      220 kg.t-1 and 326 kg.t-1, and both the NAG and NAPP results indicated that the
      tailings had high acid forming potential. NAG was more accurate than NAPP in
      predicting acid forming potential of the tailings due to the uncompleted
      oxidization of pyritic sulfur. Analysis of samples from two profiles test
      indicated that the acidification major occurred on the surface (0-20 cm) of the
      tailings because of limited oxygen diffusion and had little effects on the
      tailings at lower horizons. pH values were negatively related to EC, indicated
      that the acid released accelerate dissolution of the solid matrix and increase in
      both cations and actions in solution, the extractable Pb, Zn, Cu and Cd at the
      acidifying tailings surface.

PMID- 11507896
TI  - [Ecological analysis and optimization design for agricultural landscape of
      coastal zone along Radial Submarine Sand Ridges in north Jiangsu].
AB  - The Radial Submarine Sand Ridges (RSSR) on the inner shelf of the Southwestern
      Yellow Sea is one of the largest of such system in the world. It was developed
      into great amount of land which is mainly used for agriculture. However, the
      coastal zone is facing many serious environmental and resources problems such as
      coastal erosion, ecological fragility and over- and abuse of coastal resources.
      Based on comprehensive field survey, this paper proposes optimization allocation
      and design of agri-landscape spatial structures targeting an integrated
      improvement in agricultural ecology, economy and amenity of the region as well as
      implementation of sustainable development strategy. As a case study,
      rectification approaches and conceptual optimization design for Rudong County are
      proposed and discussed.

PMID- 11507897
TI  - [The modified process for preparing natural organic polymer flocculant chitosan].
AB  - The modified process for preparing chitosan from crab or lobster shells was
      developed. In the decalcification stage, 10% HCl was used as soaking solution
      with addition of a small quantity of A as a promoter, and the mass ratio of
      reactants was 10% HCl:A:crab or lobster shells = 3.5:0.5:1, continuously stirring
      the crab or lobster shells at 30 degrees C for 3 h in place of simply soaking the
      crab or lobster shells at room temperature for 16-24 h in the previous process.
      In the deacetylation stage, 40% NaOH solution was used with addition of a small
      quantity of B as a promoter, and the mass ratio of reactants was 40%
      NaOH:B:chitin = 4:0.2:1, keeping reaction at 105 degrees C for 2 h in place of at
      115 degrees C for 6 h in the previous process. By this new process, the cost of
      the raw materials used for preparing chitosan was cut down 49%, the preparation
      time was shortened by one half, and the main properties of this chitosan such as
      viscosity, deacetylation and molecular weight all approached or exceeded those of
      the Sigma' commercial chitosan (Chitosan C-3646).

PMID- 11507898
TI  - [The distribution and natural degradation of cyanide in goldmine waste-solid and
      polluted soil].
AB  - The farmland and river were seriously polluted by cyanide because one goldmine
      tailing dam collapsed in 1995. 3 and 4 years after the accident, the cyanide
      distribution in the polluted farmland and the abandoned tailing dam was studied.
      The results indicated that natural degradation of cyanide in soil section was
      slower than in natural water body. The cyanide transference in soil section was
      similar to freely soluble salts. In arid and semiarid area, cyanide can be highly
      enriched in the salt shell which content degrading 4 years even higher than the
      fresh tailing slurry. One side the viscidity layer in the soil section can partly
      prevent cyanide transference to groundwater, on the other side the result can
      cause the cyanide highly enrich in the viscidity layer. According to character of
      cyanide natural degradation in soil the measurement of prevention and cure soil
      pollution by goldmine tailing dam collapsing was brought forward.

PMID- 11507899
TI  - [Application of DNDC model in estimation of CH4 and N2O emissions in agricultural
      ecosystems in Yangtze River Delta].
AB  - It was paid attention that CH4 and N2O emission from agricultural soil in Yangtze
      River Delta where there is most advanced agricultural region in China. In this
      paper, a regional-scale biogeochemical model DNDC was validated on available
      field measurement. Then it was used to estimate CH4 and N2O emission in Yangtze
      River Delta to be 1.69 (1.29-2.09) Tg.a-1 and 0.019 (0.014-0.024) Tg.a-1,
      respectively. They are about 16.7% and 6.1% of the national total CH4 and N2O
      emissions from agricultural ecosystems, respectively.

PMID- 11507900
TI  - [A comparison between a submerged membrane bioreactor and a conventional
      activated sludge process].
AB  - A comparison between a submerged membrane bioreactor (MBR) and a conventional
      activated sludge process (CAS) was carried out under similar operational
      conditions. MBR demonstrated a more stable and excellent effluent quality than
      CAS. Its effluent COD concentration was 55.5 mg/L on average, much lower than
      that of CAS (79.7 mg/L). Soluble microbial products accumulated in the MBR during
      the first 120 days in operation due to membrane interception of macromolecules,
      but these accumulated substances were degraded at last with microbial
      acclimation. No similar phenomenon was observed in the CAS system. Compositions
      of the CAS effluent, MBR supernatant and membrane permeate were found quite
      different. In the CAS effluent and MBR supernatant, both macromolecules with MW >
      60,000 and small molecules with MW < 3,000 were dominant and macromolecules had a
      much larger occupation in the MBR supernatant. In the membrane permeate, however,
      small molecules with MW < 3,000 were the major component. The relatively small
      floc size in the MBR was proved favorable to improve oxygen transfer rate.

PMID- 11507901
TI  - [Removal of arsenic from dispersed drinking water by iron oxide-coated sand].
AB  - The iron oxide-coated sand(IOCS) was developed by treating normal river sand with
      molysite and investigated by batch, column tests and autoptic experiment to
      evaluate it's ability of eliminating arsenic from dispersed drinking water. The
      results showed that IOCS was relatively stable and can be seen iron oxide
      distributedly patched the surface of sand by scan electron microscope. IOCS
      needn't any activation pretreatment. It reached the maximum adsorption within 30
      60 min. The removal percentage of arsenate was decreased but the one of arsenite
      had little change when the pH varied from 5 to 9. And the arsenic adsorption
      matched the Langmuir isotherm. In 5 circles of runs, it treated 408-426
      (arsenite) beds and 390-412(arsenate) beds volume of water with 75 g(50 ml) IOCS
      respectively when the influent arsenic concentration was 1.0 mg.L-1. And the
      arsenic percentage recovery was above 94% when regenerating the IOCS by 0.2 mol.L
      1 NaOH. The home simulation unit contained IOCS 3.0 kg produced 209 L and 198 L,
      196 L and 185 L of water when the influent arsenate or arsenite concentration was
      1.0 mg.L-1, and 200 L arsenic free water with the influent arsenic 0.202-1.733
      mg.L-1 during the field experimental period. The water quality was not affected
      by the adsorbent. With low-cost and simple operation, the IOCS should be a
      promising novel medium for arsenic removal in dispersed drinking water.

PMID- 11507902
TI  - [Characteristics of granular sludge during start-up of the internal circulation].
AB  - The quick start-up of the laboratory scale IC reactor and the characteristics of
      granular sludge during start-up were studied in this paper. The results showed
      that the first start-up of IC reactor could be finished in 20 days, while
      secondary start-up only needed 15 days with COD loading rate of 12-15 kg.(m3.d)-1
      and COD removal larger than 85%. During start-up, the characteristics of granular
      sludge changed greatly: average granular diameter was increased from 0.88 mm to
      1.25 mm; average settling velocity was enhanced from 35.4 m.h-1 to 105.17 m.h-1;
      methanogenic activities of the granular increased up to 4 times as large as the
      seeded sludge; the main methanobacteria was changed from Methanothrix to
      Methanococcus and Methanobacterium.

PMID- 11507903
TI  - [Total water pollution load determining on Tianxi catchment area in Shenyang
      city].
AB  - This paper analysed and determined the total water pollution load of Tianxi
      catchment area in Shenyang city systematically; by giving the reliability
      measurement to the total pollution load, put forward the suggestions to improve
      the system information reliability. It was found that to strengthen monitoring
      and investigation for the pumping station is of great advantage to control the
      pollutants of heavy metals, moreover, by adding monitoring to the Huanglatuozi
      section of Xi river, not only can the pollution load be identified clearly but
      also organic pollutants can be controlled more accurately and timely.

PMID- 11507904
TI  - [Removal of NH4(+)-N from polluted water resources by bioremediation of biofilm
      process with elastic packing & micropore aerator].
AB  - The effect of NH4(+)-N removal in the polluted raw water of water sources by the
      bioremediation action of the biocontact oxidation process with the elastic
      packing and micropore aerator was studied in this paper. The research results
      showed the bioremediation process can reach a removal ratio of 64%-95% for NH4(+)
      N of water sources under the condition of ordinary temperature 20 degrees C-27
      degrees C, CODMn 7-14 mg/L, NH4(+)-N 0.7-2.0 mg/L in the water sources and the
      running parameters HRT 1.4 h, gas and water ratio 0.5:1, and DO 7-9 mg/L for the
      bioremediation process and a removal ratio of 40%-63% for NH4(+)-N of water
      sources under the condition of low temperature 7 degrees C-12 degrees C, CODMn 6
      11 mg/L, NH4(+)-N 1.2-8.0 mg/L in the water sources and the running parameters
      HRT 1.4 h, gas and water ratio 0.5:1, and DO 8-10 mg/L for the bioremediation
      process.

PMID- 11507905
TI  - [Accumulation of heavy metals in urban soils and impacts on microorganisms].
AB  - Compared with rural soils, urban soils in Aberdeen city possessed obviously
      different microbial features: higher in microbial basal respiration strength, and
      microbial ecophysiological parameters Cmic/Corg and qCO2, but lower in microbial
      biomass, also much more rapid in consuming carbon sources deduced from Biolog
      data. Urban soils showed different characteristics in heavy metals as well.
      Apparent accumulation of Pb, Zn, Cu, Ni were observed, in which Pb mainly related
      with iron oxides, Ni, Zn existed in residual forms, Cu exhibited same importance
      of different chemical forms but for soluble forms. Principal component analysis
      results reflected the overwhelming factor to control the difference of microbial
      features between urban and rural soils was soluble Pb, then soluble Zn, soluble
      and organic bonded Cu and Ni also contributed in some degree.

PMID- 11507906
TI  - [Kinetics of interaction of H+ with constant and variable charge soils].
AB  - The kinetics of interaction of H+ ions with constant and variable charge soils
      were studied, among which changes of H+ concentration, positive surface charge
      and soluble Al with time and their influencing factors were investigated in
      detail. The results showed that the consumption processes of H+ ions in both
      constant and variable charge soils could be divided into fast and slow processes,
      but the manifestations and influencing factors were different for the two types
      of soils. The variations in positive surface charges for variable and constant
      charge soils, due to the difference in the contents of free Fe-oxides, are
      remarkably different and thus can not be modeled mathematically in the same
      manner for the two types of soils. The variations in soluble Al for both variable
      and constant charge soils were controlled by the components, solubility and
      solution kinetics of dominant clay minerals in soils, and could be described by
      both modified Elovich and two-constant rate equations mathematically.

PMID- 11507907
TI  - [Effect on sewage sludge composting with different aeration modes].
AB  - Two kinds of aeration modes, five kinds of amendment were tested in sewage sludge
      composting. The pile temperature rose to the set temperature(60 degrees C) and
      could maintain some thermophilic period. The pathogen reduction of sewage sludge
      compost met with the control standard. Compared with positive forced aeration,
      the natural aeration combined with positive forced aeration made the pile
      temperature rise faster and consume less energy. However, the positive forced
      aeration could accelerate the moisture content reduction and the organic matter
      degradation of mixtures of sewage sludge and amendment. The moisture content of
      raw materials affected the composting process very much, and should be less than
      80%. The pH value of raw materials need to be adjusted during the sewage sludge
      composting process.

PMID- 11507908
TI  - [UV photolysis mechanism of CCl4 and CHCl3 in water].
AB  - The photolysis mechanism of CCl4 and CHCl3 in water was studied by using
      transient absorption spectra. The results showed that aqueous CCl4 was
      dissociated into CCl3 and Cl radicals by 248 nm laser, and CHCl3 was dissociated
      into CHCl2 and Cl radicals after adding C6H6. The radicals CCl3 and CHCl2 were
      able to react with O2 to form CCl3O2 and CHCl2O2 respectively, or to form C2Cl6
      and C2H2Cl4 without O2. The rate coefficients of some reactions were obtained.

PMID- 11507909
TI  - [The character changes and maturity of sewage sludge aerobic co-composting with
      various bulking agents].
AB  - In Aerobic co-composting of four bulking agents and de-watered sewage sludge, the
      records of temperature, moisture, organic matter, pH and conductivity with time
      showed the composting could be successfully processed. The changes of chemical
      parameters, water soluble organic carbon, nitrate, ammonium and biological
      parameter Cress Germination Index(GI) with time during the composting process
      were investigated. Ammonium concentration was found to be an important chemical
      factor affecting Cress Germination Index and had significant negative correlation
      with GI which could be used as a good index of compost maturity in this study.
      The value of ammonium which changed with the initial components in composting
      would be 0.5-1.4 mg/g at the end of the processes in all composts.

PMID- 11507910
TI  - [Effect of phosphate on the exchangeable form and the bioavailability of
      exogenous neodymium in soil].
AB  - Effects of phosphate on the exchangeable form and the bioavailability of
      exogenous neodymium (Nd) in soil were studied with 147Nd isotopic tracer.
      Exchangeable Nd was extracted with solution (pH8.2) of NaAc. The results
      indicated that Nd beyond 99.5% was adsorbed by soil whether phosphate exists in
      soil or not. Phosphate can precipitate dramatically Nd3+. And the Nd phosphate
      precipitates may set limits on the concentration of exchangeable Nd observed in
      soil. KH2PO4 ranging from 0.3 g.kg-1 to 1.5 g.kg-1 make a uniform impact on the
      exchangeable form of Nd. In addition, phosphate in soil can inhibit wheat
      seedling to absorb Nd. The concentration of exchangeable Nd is correlated
      significantly with the content of Nd in wheat seedling.

PMID- 11507911
TI  - [Accumulation, chemical fractions and phytoavailability of Cr in tannery sludge
      amended soils].
AB  - The phytoavailability of various fractions in the tannery sludge amended soils
      was investigated employing a sequential extraction procedure as well as seedling
      culture experiment. The results showed that 2 mol/L HCl extractable Cr could be
      the major fraction of soil Cr available to the plants. When the Cr content in
      soil was about 220 mg/kg, the Cr concentration of in plant reached maximum of
      23.5 mg/kg, which was hardly approachable in field condition.

PMID- 11507912
TI  - [Distribution of polycyclic aromatic hydrocarbon in core sediments of the Bohai
      Straight].
AB  - Thirteen compounds of PAHs were identified by GC in the core sediments of Bohai
      Straight (S44 and T4 Stations). The distribution and source identification were
      studied with the two core sediments. The total concentrations changed from 60.3
      ng/g to 2076.5 ng/g. Though the contamination of PAHs in the study area is quite
      modest, some carcinogenic compounds were detected in most samples. From the
      indicators such as Pen/Anth and Fluo/Pyr etc. the dominated origin of PAHs in S44
      Station is pyrolytic origins. However, in T4 Station, a mixture of pyrolysis and
      petroleum origin is suggested in this area. The distribution of PAHs in the core
      sediments also could be a good indicative of the contribution of human activity.

PMID- 11507913
TI  - [Effect of pH on copper sorption by the loess and its species].
AB  - To study the effect of pH on copper sorption and species, loess was taken as
      sorbent in this research, and control experiments were conducted with quartz. All
      the curves of sorption amount-pH showed three regions, namely, sorption amount
      increased slowly at low pH, then increased quickly with the rise of pH, and
      reached the maximum amount at high pH. Copper of sorbed, exchangeable and bound
      to carbonate decreased with the increase in sediment concentration at constant Cu
      concentration, and increased with the increase in Cu concentration at constant
      sediment concentration. The MINTEQA2 model results showed that the proportions of
      precipitates and their compositions were different for loess and quartz, and the
      proportions of precipitates decreased with the concentrations of loess.

PMID- 11507914
TI  - [The sonochemical-degradation mechanism of toluene in aqueous solution].
AB  - The sonochemical degradation of toluene in the airproof aqueous solution was
      studied, and the mechanism and course of degradation was explored. It was found
      that the sonication time had great effect on the removal rate of toluene, and the
      degradation followed a pseudo-first-order kinetic law, and 90%-95% of toluene was
      removed only after being irradiated for 40 min, types of dissolved gas and pH
      also had some effects. After aqueous solution was analyzed pH and scanned UV
      wavelength and identified components with SMPE-GC-MS, results confirmed that
      radical-oxidation controlled the sonochemical-oxidation of toluene, and main
      middle-products included benzaldehyde, bibenzyl, dibutyl phthalate, et al., final
      products were carbon dioxide and water.

PMID- 11507915
TI  - [Evaluation and fate of the organic chlorine pesticides at the waters in Jiulong
      River Estuary].
AB  - 18 Organochlorine Pesticides at the water(surface water and porewater) in Jiulong
      River Estuary were determined. The range of organochlorine pesticides at surface
      water was 51.3-2479 ng/L, and the concentration in porewater was 266-33,355 ng/L.
      The results showed that the organochlorine pesticides were removed in the estuary
      and the sediments were the reservior of the organochlorine pesticides. Compared
      with the results of other harbor and estuaries, it showed that the contamination
      for organic chlorine pollutants in Jiulong River Estuary was similar to those of
      others. At the same time, the risk of organochlorine pesticides in the estuary
      was evaluated.

PMID- 11507916
TI  - [Experiment of biodegradation of chlorobenzenes].
AB  - Four strains of microorganisms which were able to grow at the presence of 1,4
      dichlorobenzene 1,2,4-trichlorobenzene and hexachlorobenzene were isolated from
      the sludge collected from two different sites after incubating about 2 months.
      During the growth of the mixed microorganisims on chlorobenzenes, the
      accumulating consumption of oxygen, the microbial population curve and the
      concentration of released Cl- were investigated. The result showed that the mixed
      microorganisms were able to utilize 1,4-dichlorobenzen and 1,2,4-trichlorobenzene
      as sole carbon source and energy source. The concentration of released Cl- may
      depend strongly on the activity of the living cells. The order in which the
      chlorobenzenes were readily degraded was 1,4-dichlorobenzenez[356.7
      micrograms/(L.d)] > 1,2,4-trichlorobenzene[110.4 micrograms/(L.d)] >
      hexachlorobenzene[approximately 6 micrograms/(L.d)]. The number of the
      substituted chlorine on the chlorobenzenes directly resulted in the resistance to
      biodegradation.

PMID- 11507917
TI  - [Microbial degradation of polychlorinated dibenzo-p-dioxins].
AB  - PCDDs-degrading bacterial strains were isolated from soil and oxic-sediments
      polluted by PCDDs. One of them was identified as Pseudomonas sp. EE41. They are
      capable of growing on and degrade mono- and di-chlorinated dibenzo-p-dioxins as a
      sole carbon source. The biodegradability of TrCDD and TCDD can be enhanced
      through primary nutrient of co-metabolism of o-CDB, thus, 1,2,3-TrCDD and 2,3,7,8
      TCDD were degraded by 33% (at the concentration of 1.2 mg/L, within 3 weeks) and
      37.8% (at the concentration of 0.1 mg/L, within 3 weeks) respectively. Most
      highly chlorinated dibenzo-p-dioxins (P-CDD, H6-, H7-CDD and OCDD) tested in this
      study were accumulated in bacterial cells, but could not be degraded.

PMID- 11507918
TI  - The effect of an oral hygiene program on oral levels of volatile sulfur compounds
      (VSC).
AB  - Volatile sulfur compounds (VSCs) produced by bacteria in niches of the oral
      cavity play a major role in the etiology of bad breath, and can be easily
      detected by a portable sulfide monitor (Halimeter). To investigate the effect of
      an oral hygiene program on VSC levels, Halimeter readings were taken from 55
      healthy dental students during a course in oral hygiene training, including
      instruction on brushing, flossing and professional tooth cleaning. Ten students
      who received no oral hygiene training served as a negative control. The oral
      hygiene status was measured using the papillary bleeding index (PBI). PBI and VSC
      values did not show significant changes during the study period of 10 weeks in
      the control group. In the test group, PBI values significantly decreased compared
      to baseline and the control, indicating that the oral hygiene program had a
      benefit on the oral hygiene status. The VSC values also decreased significantly
      during the study period compared to baseline and the control. It was concluded
      that in a group of dental students, a thorough oral hygiene training program was
      capable of reducing the oral level of VSC Halimeter readings.

PMID- 11507919
TI  - Caries inhibition in rats by a sodium fluoride, tripolyphosphate toothpaste with
      whitening and anti-tartar properties.
AB  - The anti-caries properties of a silica-based, sodium fluoride (NaF) toothpaste
      containing sodium tripolyphosphate (NaTPP) with tooth whitening and anti-tartar
      properties (Aquafresh Whitening), in specific pathogen-free Osborne-Mendel rats,
      were assessed in this study. A silica-based, fluoride-free placebo containing
      NaTPP, and a NaF-containing silica-based USP reference standard toothpaste were
      used as negative and positive control toothpastes, respectively. Sixty weanling
      rats were randomly distributed into groups of 20; all were inoculated with S.
      mutans 10449S, ate cariogenic diet 2000, and drank demineralized water ad
      libitum. Each toothpaste, packaged in coded tubes, was applied to the dentitions
      of the rats' teeth for one minute, twice daily on weekdays, and once daily on
      weekends and holidays. Both the NaF/NaTPP-containing and the NaF-containing USP
      standard toothpaste groups had lower total enamel caries scores (41 to 45%) than
      the group treated with the fluoride-free NaTPP-containing placebo. Similar
      dimensioned differences were evident both at smooth surface and sulcal enamel
      sites, and in dentinal sites. All were statistically significant at p < 0.001.
      There were no statistically significant differences at any tooth surface category
      site between the two fluoride-containing toothpastes' effects. It is thus
      apparent that Aquafresh Whitening has the anticaries benefit of a USP reference
      standard NaF toothpaste.

PMID- 11507920
TI  - Laboratory evaluations of a toothbrush with diamond-shaped filaments for
      stiffness and efficacy.
AB  - The purpose of these studies was to evaluate four toothbrushes with a similar
      flat profile for stiffness and efficacy in removing artificial plaque deposits
      from interproximal areas, or depth of removal from broad tooth surfaces, and to
      relate these findings to bristle stiffness. The test toothbrush had 5-mil
      diameter, elongated diamond-shaped bristles (D). Three toothbrushes contained 5
      mil (5), 6-mil (6), or 7-mil (7) diameter round bristles. Stiffness studies were
      performed using the ISO 8627 method. In the efficacy studies, toothbrushing was
      conducted with a vertical or horizontal brushing motion on simulated anterior or
      posterior teeth using a brushing weight of 250 g. The bristles were placed at a
      90 degrees angle to the tooth surface, and brushing was performed for 15 seconds
      at two strokes per second with 50 mm strokes. Each of the toothbrush designs was
      tested 24 times. Interproximal access efficacy (IAE) was recorded as the maximum
      width of simulated plaque deposit removed. Depth of deposit removal (DDR) was
      determined using a color comparative scale, where 0 = no deposit change and 4 =
      maximum removal. The averages of wet and dry stiffness measurements were found to
      be 7 > D > 6 > 5; all values were in the range accepted as soft texture. The
      means for total IAE were ranked D > 5 > 6 > 7, and total DDR mean rankings were D
      > 7 > 6 > 5. For the round bristles, stiffness was inversely related to IAE and
      paralleled the DDR rankings. Using ANOVA, the D and 5-mil toothbrushes had
      significantly higher (p < 0.05) IAE means compared to the 6- or 7-mil products.
      The D toothbrush had significantly higher (p < 0.05) DDR means than the 5-mil
      product. The diamond-shaped bristles in these flat profile products resulted in
      improved depth of deposit removal compared to the same design with 5-mil round
      bristles.

PMID- 11507922
TI  - Comparison of the mechanical effects of a toothbrush and standard abrasive on
      human and bovine dentine in vitro.
AB  - Dentine abrasion is an important possible side effect of individually used
      mechanical oral hygiene products. Since human teeth are sometimes not available
      in sufficient numbers for research purposes, bovine teeth are often used as a
      substitute for in vitro tests of dentine abrasion. The aim of the present
      comparative study was to determine the mechanical effects of a manual toothbrush
      and a standard abrasive on human and bovine dentine under standardized
      conditions. Roots of human and bovine teeth were radioactivated and subjected to
      standardized machine brushing using a manual toothbrush and a standard abrasive
      slurry. Dentine abrasion was assessed by measuring radioactive phosphorus
      contained in the slurry after brushing. Non-radioactive human and bovine roots
      were brushed in the same machine, and the generated surface roughness was
      assessed using profilometry. Artificially stained human and bovine roots were
      brushed as described, and the cleaning effect was expressed as the extent of
      stain-free surfaces after different brushing times. The results for abrasion and
      surface roughening found with bovine and human dentine suggest that if
      standardized methods are used, roots of bovine mandibular front teeth can be used
      in place of human roots for in vitro studies of the mechanical effects of
      toothbrushes and toothpastes on dentine. The use of bovine dentine for measuring
      the cleaning effects of these products is, however, not recommended.

PMID- 11507921
TI  - A four-day study to evaluate the anti-plaque efficacy of an experimental
      triclosan-containing dentifrice.
AB  - Four-day, non-brushing studies have been used successfully to demonstrate the
      anti-plaque efficacy of triclosan-containing dentifrices. The treatment effects
      observed are variable, likely due to differences in formulation, study design and
      measurement techniques. This randomized, double-blind crossover study was
      conducted to evaluate the anti-plaque efficacy of an experimental, multiple
      benefit, triclosan-containing dentifrice versus two currently marketed sodium
      fluoride dentifrices in a four-day, lingual-brushing model on subjects in
      Beijing. People's Republic of China. Subjects brushed the lingual surfaces for 30
      seconds, and before expectorating, swished the saliva/dentifrice slurry over the
      buccal surfaces for an additional 30 seconds. This procedure was repeated.
      Subjects performed their assigned brushing regimen twice daily for four days
      under supervision. On Day 5, plaque was measured using the Turesky Modification
      of the Quigley-Hein Plaque Index. There were highly significant treatment effects
      in favor of the experimental triclosan-containing dentifrice for whole mouth,
      buccal and lingual sites when compared to either of the sodium fluoride
      dentifrices (p < 0.0001).

PMID- 11507923
TI  - Laboratory evaluation of anti-biofilm agents for use in dental unit waterlines.
AB  - Dental unit waterline biofilm has been recognized as a potential point of
      contamination and a risk to patients with any level of immunocompromise. Biofilm
      in dental unit waterlines, once established, has proven formidable to efforts in
      disinfection/disruption. This project compared standardized evaluation techniques
      by assessing the efficacy of a variety of agents that have been reported or
      suggested as useful in surface disinfection and/or antiseptic protocols. The
      zones of inhibition, minimum inhibitory/bactericidal concentrations and use
      dilution with stainless steel carrier replicates tests assessed the disinfection
      of planktonic organisms using standardized microbial testing procedures. The
      disruption and/or disinfection of planktonic and biofilm organisms within
      naturally occurring dental unit waterlines were evaluated by culture and scanning
      electron microscopy. The six commercially available antimicrobial agents used to
      assess the techniques were bleach (sodium hypochlorite), Cavicide,
      glutaraldehyde, Listerine Antiseptic, Peridex and Sterilex Ultra. Comparisons
      between the results for each technique evaluated were determined for each
      product. All six agents demonstrated antimicrobial efficacy at the working
      concentrations designated by the manufacturers. Biofilm matrix elimination
      evaluated by scanning electron microscopy found virtually 0% elimination by
      glutaraldehyde to an estimated 90% elimination by Sterilex Ultra and bleach after
      one treatment. Treatment with Cavicide, Listerine Antiseptic and Peridex resulted
      in negligible elimination of the biofilm matrix. For comparability, the use of
      standardized testing techniques to evaluate a disinfection agent's efficacy
      against dental unit waterline contamination is essential. This project
      demonstrates a model system for evaluating disinfection agents potentially useful
      in the management of dental unit waterline biofilm, and should assist in
      educating the dental clinician in the appraisal of existing and future product
      claims.

PMID- 11507924
TI  - A new and improved "dual action" whitening dentifrice technology--sodium
      hexametaphosphate.

PMID- 11507925
TI  - Extrinsic stain removal with a sodium hexametaphosphate-containing dentifrice:
      comparisons to marketed controls.
AB  - Repeated exposure to chlorhexidine and tea has long been recognized to promote
      extrinsic tooth stain. Previously, the merits of a modified, rapid clinical trial
      model using chlorhexidine and tea in combination with restricted brushing to
      accelerate staining have been established. A nine-week randomized and controlled,
      examiner blind, parallel group clinical trial was conducted to compare selected
      chemical and mechanical approaches for stain removal using this model. After
      prophylaxis, stain was induced during a 3-week pre-treatment period, and then the
      healthy adult volunteers were randomized to one of three treatment groups: an
      experimental whitening dentifrice containing a combination of sodium
      hexametaphosphate and soluble pyrophosphate; a marketed alumina-based high
      abrasive dentifrice; or a lower abrasive control dentifrice. At baseline, three
      and six weeks, dental stain was measured on the facial and lingual surfaces of
      the eight anterior teeth using the Lobene index. A total of 94 subjects completed
      the study. Both the chemical and abrasive dentifrices showed statistically
      significant reductions in stain area (p < 0.05) relative to the control after
      three weeks. After six weeks, adjusted mean stain area scores were 0.35, 0.41 and
      0.49 for the sodium hexametaphosphate, alumina and regular dentifrice groups,
      respectively. While the alumina dentifrice showed only a directional benefit, the
      sodium hexametaphosphate differed statistically (p = 0.023) from the control.
      Subjects in both the chemical and abrasive dentifrice groups showed statistically
      significant reductions relative to baseline for Lobene composite stain, stain
      area and stain intensity (p < 0.05) at six weeks. There were no statistically
      significant differences in stain levels between the sodium hexametaphosphate and
      alumina dentifrice groups at any time. This study demonstrates that following six
      weeks of treatment, sodium hexametaphosphate-containing dentifrices are effective
      in removing extrinsic tooth stain, with performance at least comparable to that
      seen with more abrasive dentifrices.

PMID- 11507926
TI  - Extrinsic stain prevention with a combination dentifrice containing calcium
      phosphate surface active builders compared to two marketed controls.
AB  - A six-week, randomized and controlled, examiner blind, parallel group clinical
      trial was conducted to evaluate the stain prevention efficacy of an experimental
      whitening dentifrice containing a combination of sodium hexametaphosphate and
      soluble pyrophosphate relative to a marketed high-abrasive dentifrice and a
      marketed control dentifrice. Following the collection of baseline stain scores
      and subsequent prophylaxis, healthy volunteers were randomized to one of three
      treatment regimens, balancing for stain levels and smoking status. Throughout the
      six-week treatment period, subjects brushed twice daily with the assigned
      dentifrice while following a rinse regimen of three times daily tea and once
      daily chlorhexidine. At baseline, three and six weeks, dental stain was measured
      on the facial and lingual surfaces of the eight anterior teeth using the Lobene
      Index. A total of 96 subjects completed the study. At three and six weeks,
      adjusted stain scores were highest in the control group and generally lowest in
      the sodium hexametaphosphate group for all Lobene parameters (intensity, area and
      composite). At three weeks, stain area and composite stain scores for the sodium
      hexametaphosphate dentifrice were statistically significantly (p < 0.05) lower
      relative to the control, representing reductions of 30% and 33%, respectively.
      Similar numerical trends were observed after six weeks, with the sodium
      hexametaphosphate group showing reductions of 21% (p = 0.068) in stain area and
      26% (p = 0.055) in composite stain relative to the control. The high-abrasive
      dentifrice was directionally, though not statistically superior to the control at
      three and six weeks. All three test products were well-tolerated.

PMID- 11507927
TI  - Laboratory studies on the chemical whitening effects of a sodium
      hexametaphosphate dentifrice.
AB  - Laboratory studies were developed to permit the evaluation of chemical actions of
      toothpaste components in the non-abrasive prevention and removal of tea stains.
      Powdered hydroxyapatites were used as substrates for adsorption of tea
      chromogens. Pre-treatment with a sodium hexametaphosphate dentifrice (Crest Dual
      Action Whitening) reduced tea adsorption to powdered apatite, while post
      treatments of pre-stained powder resulted in desorption of tea components. These
      results exemplified the chemical actions of condensed calcium phosphate surface
      active builders toward dental stain removal and prevention. A cycling synamel
      chip model permitted the study of stain prevention, including salivary pellicle
      formation and chlorhexidine enhancement of dental staining by tea chromogens.
      Staining was evaluated by image analysis of color development. Under these
      conditions, condensed phosphate dentifrices were observed to produce superior
      prevention of stain accumulations, with Crest Dual Action Whitening dentifrice
      providing stain prevention superior to a variety of commercial dentifrices,
      including Colgate Total, Aquafresh Whitening, Colgate Tartar Control Whitening,
      Mentadent Baking Soda and Peroxide Whitening, Close-Up Whitening, Crest Tartar
      Control and Crest Regular Cavity Protection.

PMID- 11507928
TI  - Anticalculus efficacy and safety of a novel whitening dentifrice containing
      sodium hexametaphosphate: a controlled six-month clinical trial.
AB  - This study was undertaken to establish the tartar control efficacy and long-term
      safety of a new dentifrice containing sodium hexametaphosphate. In a randomized,
      examiner blind, parallel group clinical trial, the experimental dentifrice with
      7% sodium hexametaphosphate (5% hexametaphosphate anion), a non-abrasive cleaning
      agent that provides whitening and tartar control benefits, was compared to two
      currently marketed controls, a regular sodium fluoride dentifrice and a
      triclosan/copolymer dentifrice. The 8-month trial model included a 2-month
      pretest period to establish calculus formation after prophylaxis, and a 6-month
      test period to evaluate anti-calculus efficacy and safety. Following the pretest
      period, 551 subjects were allocated to one of the three treatment groups and then
      monitored for calculus accumulation and soft tissue tolerance. After 6 months,
      the sodium hexametaphosphate group exhibited superior calculus inhibition
      compared to the regular sodium fluoride dentifrice and triclosan/copolymer
      dentifrice (p < 0.01). Over the 6-month observation period, the sodium
      hexametaphosphate and the marketed control dentifrices were comparable in terms
      of adverse event type and severity, and no subject discontinued treatment due to
      an oral soft tissue adverse event.

PMID- 11507929
TI  - Comparative intraoral tolerance of sodium hexametaphosphate and pyrophosphate
      antitartar dentifrices.
AB  - A randomized, controlled clinical trial was conducted to assess the relative
      acute oral tolerance of a novel, dual-phase, tartar control dentifrice containing
      7.0% sodium hexametaphosphate (5% hexametaphosphate anion). In this 4-day study,
      159 healthy adult volunteers were randomly assigned to the experimental sodium
      hexametaphosphate dentifrice or a marketed, single-phase, antitartar dentifrice
      control containing 5.0% ionic pyrophosphate. A detailed oral soft tissue
      examination and interview were conducted each day by blinded evaluators to elicit
      clinical signs and symptoms associated with ad libitum use of the assigned
      dentifrice. A total of 24 subjects (15% of the study population) had new
      symptoms/signs after baseline. By treatment, 9% of subjects in the sodium
      hexametaphosphate group had new findings, compared to 21% of subjects in the
      pyrophosphate group, and these groups differed statistically (p < 0.03, two
      sided) with respect to occurrence. In addition, onset, severity, duration and
      clinical presentation were generally milder in the sodium hexametaphosphate group
      compared to the pyrophosphate control. Only one subject (in the pyrophosphate
      group) discontinued treatment early due to oral intolerance. In this study, the
      7.0% sodium hexametaphosphate dentifrice was well-tolerated, with significantly
      fewer symptoms and superior overall tolerance compared to the marketed antitartar
      dentifrice control.

PMID- 11507930
TI  - In vitro studies of the anticalculus efficacy of a sodium hexametaphosphate
      whitening dentifrice.
AB  - Laboratory studies involving crystal growth inhibition and plaque biofilm
      calcification were conducted to confirm the anticalculus potential of a dual
      action whitening dentifrice containing sodium hexametaphosphate, a novel, enamel
      safe, antitartar agent. Calcium hydroxyapatite crystal growth was significantly
      inhibited following direct supernate treatments by hexametaphosphate in solution
      and when formulated into the dual-action whitening dentifrice. Similarly, plaque
      biofilm calcification was significantly inhibited by supernate treatments of the
      hexametaphosphate whitening dentifrice. The activity of hexametaphosphate
      dentifrice in plaque biofilm calcification protocols exceeded that produced by
      commercial dentifrices containing polycarboxylic acid, metal ion and
      pyrophosphate tartar control ingredients. Results predict excellent clinical
      activity for hexametaphosphate dentifrice for the prevention of supragingival
      calculus formation. Published double-blind, randomized clinical studies confirm
      the validity of these laboratory models for the screening of potentially improved
      tartar control ingredients.

PMID- 11507931
TI  - Hexametaphosphate effects on tooth surface conditioning film chemistry--in vitro
      and in vivo studies.
AB  - These studies compared the effects of Crest Dual Action Whitening dentifrice with
      sodium hexametaphosphate and control commercial dentifrices on the surface
      chemistry of conditioning film-coated dental enamel in vitro and in vivo.
      Conditioning film chemistry was studied by measurements of film thickness,
      ability to wet the surface/surface energy, conditioning film chemical composition
      and zeta potential. Laboratory and in vivo studies demonstrated that brushing and
      chemical-only treatment of pellicle-coated enamel surfaces produced marked
      changes in surface chemistry. Brushing of surfaces with all commercial
      dentifrices significantly reduced pellicle film quantity. Effects on non-brushed
      areas, of significance in the clinical situation, were different for different
      dentifrices. For dentifrice chemical treatments, calcium phosphate surface active
      builders, such as pyrophosphate and hexametaphosphate, produced stronger effects
      than standard (non-tartar control) dentifrices, peroxide baking soda dentifrices
      and dentifrices formulated with carboxylate polymers, viz. Colgate Total with
      copolymer. Crest Dual Action Whitening hexametaphosphate dentifrice removed more
      pellicle conditioning film, produced a lower zeta potential, produced the largest
      changes in film composition and had the greatest impact on surface free energies
      of the tested dentifrices. Crest Dual Action Whitening dentifrice also produced
      lasting changes in the reacquisition of pellicle conditioning film, as
      established by in vitro cycling immersion studies. Crest Dual Action Whitening
      dentifrice produced stronger and more lasting effects on surface film chemistry
      than low molecular weight pyrophosphate (Crest Tartar Control) or other polymeric
      based dentifrice systems (Colgate Total). These surface chemistries may
      contribute to the unique clinical actions of hexametaphosphate established in
      recently reported, randomized clinical studies of tartar control, stain
      prevention and stain removal effects.

PMID- 11507932
TI  - Bacterial detachment from salivary conditioning films by dentifrice supernates.
AB  - This study compared the detachment by supernates of nine different dentifrices of
      four oral bacterial strains adhering to a salivary pellicle in a parallel plate
      flow chamber. Ultra-thin bovine enamel slabs were coated for 1.5 h with human
      whole saliva. Following buffer rinsing, a bacterial suspension of Streptococcus
      oralis, Streptococcus sanguis, Streptococcus mutans or Actinomyces naeslundii was
      perfused through the flow chamber at a shear rate of 30 s-1 for four hours, and
      the number of adhering bacteria n4h was enumerated by image analysis after buffer
      rinsing at the same shear rate. Then, a 25 wt%-dentifrice/water supernate was
      perfused through the flow chamber for four minutes, followed by eight minutes of
      buffer rinsing and another enumeration of the number of bacteria that had
      remained adhering nad. Finally, an air-bubble was passed through the flow chamber
      to mimic the occasionally high detachment forces occurring in the oral cavity,
      and the adhering bacteria nab were counted again. On average, S. sanguis was the
      easiest to detach (73% averaged over all dentifrice supernates), while A.
      naeslundii was the most difficult (22% on average). The combined detachment of
      bacteria by dentifrice supernates and air-bubble ranged from a low of 16% to a
      high of 80%. Dentifrices containing pyrophosphate and polymeric polyphosphate
      (hexametaphosphate) surface active ingredients appeared to produce the most
      consistent and strongest desorption effects on plaque bacteria. Factors
      apparently important to bacterial detachment from pellicle-covered tooth surfaces
      by dentifrice formulations include the nature of adhesion of bacterial strains
      and chemical composition of the dentifrice formulations, including pH, surfactant
      system and the effect of added ingredients (dispersants, metal ions, peroxides,
      baking soda).

PMID- 11507933
TI  - Anticaries and hard tissue abrasion effects of a "dual-action" whitening, sodium
      hexametaphosphate tartar control dentifrice.
AB  - A series of "profile" laboratory studies was conducted to confirm the anticaries
      potential and hard tissue safety of a novel sodium hexametaphosphate dentifrice
      technology which provides dual-action tooth whitening (i.e., stain prevention as
      well as stain removal), while simultaneously providing improved anticalculus
      action. Under remineralization pH cycling conditions, the dual-action whitening
      dentifrice produced lesion fluoridation comparable to a conventional NaF
      dentifrice. Under lesion progression pH cycling conditions, the dual-action
      whitening dentifrice produced enamel protection against caries initiation and
      progression comparable to a conventional NaF dentifrice, as well as comparable to
      a conventional tartar control dentifrice, also containing NaF. These results are
      consistent with clinical data supporting the anticaries effectiveness of NaF
      dentifrices combined with anionic tartar control inhibitors, such as
      pyrophosphate. Abrasion assessments were made using Radioactive Dentin and Enamel
      Abrasivity (RDA and REA) methods. These laboratory studies demonstrated that the
      new, dual-action whitening dentifrice produces dentin and enamel abrasivity
      similar to conventional silica-based dentifrice formulations. These in vitro
      studies verify the anticaries potential and demonstrate the hard tissue safety of
      the dual-action, sodium hexametaphosphate dentifrice.

PMID- 11507934
TI  - Removal of extrinsic stain using a 7.0% sodium hexametaphosphate dentifrice: a
      randomized clinical trial.
AB  - A nine-week, randomized and controlled clinical trial was conducted to compare
      the stain removal efficacy of a 0.243% sodium fluoride dentifrice containing 7%
      sodium hexametaphosphate (5% hexametaphosphate anion) to that of a 0.243% sodium
      fluoride control dentifrice. Following prophylaxis and a three-week pre-treatment
      period to induce extrinsic stain, healthy adult volunteers with tooth stain were
      randomized to the sodium hexametaphosphate dentifrice or the control. Stain area
      and intensity were assessed at baseline, three and six weeks. At both three and
      six weeks, the sodium hexametaphosphate dentifrice was statistically
      significantly superior to the control for all overall stain measures (p < 0.04).
      After six weeks of product usage, the sodium hexametaphosphate dentifrice
      demonstrated reductions of 29% in composite stain, 24% in stain intensity, and
      25% in stain area relative to the control. Significant reductions in composite
      stain were seen on both gingival and body regions for the sodium
      hexametaphosphate dentifrice versus the control at three and six weeks. Both
      products demonstrated favorable safety profiles, as determined by oral soft
      tissue evaluations and recording of subject-reported adverse events.

PMID- 11507935
TI  - Good food in a hospital? Dare to dream and palates will follow.

PMID- 11507936
TI  - Regional differences are part of breast cancer care.

PMID- 11507937
TI  - Do the job properly: see cataract surgery clearly.

PMID- 11507938
TI  - Practical risk management considerations for clinical E-mail in ambulatory care.

PMID- 11507939
TI  - Mandatory arbitration: will it be the answer to managing risk of employee
      lawsuits?

PMID- 11507940
TI  - EMTALA extended to ambulances not owned by hospital. Arrington v. Wong.

PMID- 11507941
TI  - U.S. Supreme Court has final say on pedicle screw litigation. Buckman Co. v.
      Plaintiff's Legal Committee.

PMID- 11507942
TI  - Parents do not have authority to refuse to consent to resuscitation of fetus born
      alive. HCA, Inc. v. Miller.

PMID- 11507943
TI  - Penalties and damages under FCA may be unconstitutionally excessive. U.S. v.
      Mackby.

PMID- 11507944
TI  - Civil monetary penalties may be liability for successor owners of facility.
      Deerbrook Pavilion, LLC v. Shalala.

PMID- 11507945
TI  - Activities outside practice of medicine may carry their own liabilities. Wright
      v. Jeckle.

PMID- 11507946
TI  - ERISA preemption of medical negligence claims against HMO's: perceived conflict
      between Pennsylvania Supreme Court and 3rd Circuit paves way for showdown in U.S.
      Supreme Court.

PMID- 11507947
TI  - Perspective. Senior drug use unique, needs management, analysts say.

PMID- 11507948
TI  - [Uncoupling proteins].
AB  - Uncoupling proteins are located in the inner mitochondria membrane. Their name is
      derived from their function: they uncouple oxidative procesess of the respiratory
      chain from ATP synthesis. Hitherto several members of the family have been
      described, the best known being UCP1. UCP1 can be expressed exclusively in brown
      adipose tissue and it is responsible for the heat production. In humans the brown
      fat disappears during the early childhood. In adults another members of the UCP
      family can be found--UCP2 and UCP3. It is widely accepted that these proteins
      affect lipid metabolism and energy expenditure. They are intensively studied
      owing to their possible use in the therapy of obesity. However, their
      physiological function has not been yet fully established.

PMID- 11507949
TI  - [Eating disorders in childhood and early adolescence].
AB  - Paper dials with specific characteristics of eating disorders in childhood and in
      early adolescence. Eating disorders can come in all ages, however, they occur
      most frequently in adolescents and in young adults. Less frequently they appear
      in childhood and in adolescence (only about 5% of patients are children below 12
      years) but they represent serious challenge to the developmental process both at
      the biological and psychosocial level. Paper gives characteristic signs of eating
      disorders in children and specific syndromes, which occur in that developmental
      stage.

PMID- 11507950
TI  - [3-years' study of family contacts of HBsAg+ individuals].
AB  - BACKGROUND: About 50,000 HbsAg carriers exist in Czech Republic. The most
      endangered group is the family members and sex partners. On the basis of positive
      HbsAg laboratory findings we decided to offer laboratory examination of post
      infectious hepatic markers and to sero-negative also the vaccination against
      viral hepatitis B. METHODS AND RESULTS: The group of HbsAg carriers included 453
      persons (253 males and 200 females), average age 42.3 years, within the range of
      0 to 89 years. When samples were taken, 55.4% of examined persons were classified
      as "Healthy carrier". To offer of free examination and vaccination 410 family
      contacts responded. Postinfectious markers (HbsAg, antiHbsAg) were identified in
      19.0% of examined persons, 78.3% of sensitive ones were vaccinated. When
      financial costs were evaluated, it is possible to conclude that examination and
      vaccination of contacts of HbsAg positive persons in the whole Czech Republic
      using the same method and similar collaboration may require 58.5 millions Kc.
      When laboratory tests were omitted, the costs may be reduced to 59.4%.
      CONCLUSIONS: On the basis of presented data authors deduce that the legislation
      of Czech Republic should be quickly changed to include the precept of free
      vaccination of family contacts of HbsAg positive persons. In accordance with it,
      rational method of depistage of those persons and information transfer should be
      developed. Considering long-term consequences of the viral B hepatitis,
      unreplaceable role in the prevention and diagnostics of the infection have
      general practitioners.

PMID- 11507951
TI  - [Nitric oxide (NO) in a model of renal ischemia and cyclosporine toxicity].
AB  - BACKGROUND: The role of nitric oxide (NO) after the cadaveric kidney
      transplantation has not been fully clarified yet. The aim of our study was to
      examine benefits of the administration of a NO precursor--L-arginine in the model
      of renal ischaemia and after the subsequent cyclosporine (CsA) treatment, which
      simulates the state resulting from the kidney transplantation. METHODS AND
      RESULTS: 60 male rats of the Wistar strain were exposed to ischaemia for 45
      minutes. Then they were divided into six groups: 1. Controls, 2. Rats
      administered by gastric sonde with 300 mg/kg of L-arginine since the first day
      after ischaemia, 3. Rats administered in a similar way with 10 mg/kg of
      cyclosporine A, 4. Group of rats receiving both drugs in the same doses, 5. Rats
      receiving 10 mg/kg of cyclosporine A since the first day after ischaemia and L
      arginine in the dose 300 mg/kg since the seventh day, 6. Group of animals
      administered with L-arginine and cyclosporin A in the same doses with
      nonselective blocker of NO synthesis--L-NNA in the dose of 5 mg/kg. We examined
      renal functions (blood and urine levels of creatinine, urea, Na, K, Cl,
      osmolality, proteinuria), blood and urine levels of NO metabolites (NO2- and NO3
      ) in the fourth week after ischaemia. We found that L-arginine administration
      (when groups 1 and 2 were compared) decreased S-creatinine (< 0.05), it increased
      U-osmolality (p < 0.01), tubular resorption (p < 0.001), and blood levels of NO
      metabolites (p < 0.05). Changes in urine levels of NO metabolites (U-NOx/U-Cr)
      and in proteinuria were not found. In animals with renal ischaemia treated with
      cyclosporine (comparison of groups 3 and 4), L-arginine administration brought
      about a decrease of blood creatinine levels (p < 0.05), higher creatinine
      clearance (p < 0.05) and higher blood levels of NO metabolites (S-NOx; p < 0.01).
      However, differences in tubular functions, proteinuria and U-NOx/U-Cr were not
      detected. When L-arginine was added 7 days after the beginning of cyclosporine
      treatment, no significant difference was found between groups 5 and 3 and
      differences between groups 5 and 4 were similar to those between groups 4 and 3.
      Animals of the group 6 were not tested due to high mortality indicating high
      toxicity of the combination ischaemia + cyclosporine + L-arginine + L-NNA.
      CONCLUSION: Our study shows the benefits of L-arginine treatment in the renal
      ischaemia and during cyclosporine administration. The treatment should start
      immediately after the ischaemic period and at the same time as the cyclosporine
      administration. L-arginine added later has no positive effect.

PMID- 11507952
TI  - [The first successful therapeutic pulmonary lavage in pulmonary alveolar
      proteinosis in the Czech Republic].
AB  - Whole lung lavage represents a possible therapeutic method in pulmonary alveolar
      proteinosis which can lead to an improvement of blood oxygenation in the lungs.
      In the Czech Republic there has been no experience with this method so far. A
      case of 69-year-old female with idiopathic pulmonary alveolar proteinosis treated
      with the whole lung lavage sequentionally conducted is reported. The whole lung
      lavage led to the improvement of dyspnoe and arterial blood gases. Whole lung
      lavage leads to the improvement of clinical status in patients with pulmonary
      alveolar proteinosis.

PMID- 11507953
TI  - [Multiresistant tuberculosis in the Czech Republic in 1998 and causes of its
      occurrence].
AB  - Multidrug resistant tuberculosis (MDR-TB) belongs to the most serious forms of
      TB. The number of MDR-TB patients represents an indicator of the effectiveness of
      TB regimentation. The aim of the study was to determine the number of registered
      MDR-TB patients in CR in 1998 and to identify causes of the resistance. Analysis
      of clinical documentation of 27 patients with MDR-TB positive sputum was done in
      1998. According to the documentation, this form of tuberculosis was not confirmed
      in 5 persons. Out of 22 patients with confirmed MDR-TB, 21 were males and one
      female. In 3 of them we could not reveal whether they had been cured with
      antituberculotics before MDR-TB developed. Such resistance was then classified as
      an initial form. In 19 patients we found that resistance developed during
      treatment. Those cases were classified as secondary forms. In 16 patients the
      secondary resistance was related to the interruption of treatment, which was done
      wantonly by the patients in 14 cases. The consistent treatment of the sensitive
      TB is therefore the best prevention for MDR-TB development. Incidence of MDR-TB
      cases has not been influenced by immigration from countries with high rate of
      occurrence of MDR-TB.

PMID- 11507954
TI  - Leapfrog Group, other projects propel quality effort forward.

PMID- 11507955
TI  - Staff are facing big cleanup after Houston flood disaster.

PMID- 11507956
TI  - Project tackles OR sharps injuries.

PMID- 11507957
TI  - An ASC culture in a hospital center.

PMID- 11507958
TI  - Texas to license surgical assistants.

PMID- 11507959
TI  - Rapid socio-cultural change and health in the Arctic.
AB  - The colonization of the circumpolar peoples has had a profound influence on their
      health. History tells about devastating epidemics and the introduction of
      alcohol. The last 50 years have witnessed an unprecedented societal development
      in Greenland and a rapid epidemiological transition. Physical health and survival
      have improved but at the expense of mental health. The incidence of tuberculosis
      and the infant mortality rate have decreased because of improved socioeconomic
      conditions and health care. Mental health has deteriorated parallel to the rapid
      modernization of Greenlandic society. Chronic diseases are on the increase due to
      changing life styles, and environmental pollution with mercury and persistent
      organic pollutants may pose a threat to future generations of Inuit.

PMID- 11507960
TI  - Traditional food systems research with Canadian Indigenous Peoples.
AB  - Traditional food systems research with Canadian Indigenous Peoples has revealed
      many aspects of benefits and risks of the use of this food. Traditions based in
      hunting, fishing and gathering contain a great variety of species of wildlife
      plants and animals that provide rich cultural and nutritional benefits. Dietary
      change for Indigenous Peoples in Canada has resulted in the use of traditional
      food to provide usually less than 30% of total dietary energy; however this
      portion of the total diet contributes significantly more of essential nutrients.
      It also results in exposure to organochlorine and heavy metal contaminants that
      exceed the tolerable intake levels for some areas. A successful research and
      education intervention program with one British Columbia community demonstrated
      that increasing traditional food use can improve health status for vitamin A,
      iron and folic acid. It is concluded that traditional food systems are rich with
      potential for research and public health education intervention programs for
      Indigenous Peoples.

PMID- 11507961
TI  - Dietary intake among Alaska native women resident of Anchorage, Alaska.
AB  - OBJECTIVE: We summarized data from a study of Alaska Native women living in
      predominantly urban communities to assess the quality of their dietary intakes
      and compare to current US dietary recommendations. STUDY DESIGN: Descriptive
      cross sectional study of seventy-four Alaska Native women living in and around
      Anchorage, Alaska. Each completed up to four 24-h diet recalls during one year.
      Participants were enrolled in 1996 and 1997. Blood samples were analyzed for
      hematocrit, vitamin A, vitamin C, vitamin E and folate. RESULTS: Results were
      compared with current US dietary guide lines for food groups and nutrients. Mean
      intake of these women fell below recommendations for all food groups except the
      Meat and Beans Group. Mean intakes of sweets, sodium and energy from fat and
      saturated fat exceeded recommendations. Red blood cell folate levels were low in
      32% of the women. Only one-quarter of the women reported eating Native foods.
      CONCLUSIONS: The survey shows room for improvement in diet to include reduced
      intakes of saturated fat, and increased intakes of folate, calcium, and dietary
      fiber by increasing consumption of fruits and vegetables, whole grain breads and
      cereals, non-fat milk products, and Native foods.

PMID- 11507962
TI  - Traditional foods in the diet of Chukotka natives.
AB  - During several medical expeditions the recipes and technology of traditional
      foods of the indigenous population of Chukotka have been collected. Traditional
      foods are important sources of fat, protein and essential nutrients. The
      traditional diet of Chukotka natives consists of caribou meat, marine animals and
      fish, depending on the place of residence. All meat products or fish are eaten
      with local plants: roots, green leaves, berries or seaweed. Local foods are
      usually eaten raw frozen and dipped into seal oil or melted caribou fat. However,
      it has been shown that the traditional way of food preparation in the Far North
      does not meet modern sanitary and hygiene regulations. Based on data collected
      about the traditional diet of Chukotka native recipes and technology have been
      changed and approved by the Association of Indigenous Nationalities of Chukotka.
      Dietary recommendations for natives that are based on traditional eating patterns
      have been presented for consideration.

PMID- 11507963
TI  - Cod liver oil consumption, smoking, and coronary heart disease mortality: three
      counties, Norway.
AB  - It has been hypothesized that omega-3 fatty acid consumption may lessen the
      adverse effect of smoking on coronary heart disease (CHD) risk. Thus, we explored
      whether cod liver oil consumption was protective of coronary heart disease in a
      cohort of men and women participating in a cardiovascular disease screening in
      Norway. The study population was aged 35-54 at the time of the baseline screening
      conducted by the National Health Screening Service of Norway in 1977-1983. Of
      56,718 age-eligible men and women, 52,138 participated, of whom 42,612 (82%)
      completed a dietary questionnaire. Cod liver oil use was reported by 12.5%. At
      baseline, cod liver oil users had lower triglycerides, adjusting for age, body
      mass index, time since last meal and income (p < or = .05). As of December 1992,
      639 and 118 CHD deaths were observed among the men and women, respectively.
      Overall, we observed no effect of cod liver oil consumption reported at baseline
      and CHD mortality in Cox Proportional Hazards analyses [Hazard Ratio (HR) = 1.0
      (0.8-1.3)]. In analyses, stratified by smoking status, never smokers and current
      smokers showed non-significant beneficial associations between cod liver oil use
      and CHD mortality (HR = 0.7, 95% CI = 0.4-1.5; and HR = 0.8, 95% CI = 0.6-1.2,
      respectively). However, among former smokers a non-significant excess risk of CHD
      mortality was associated with cod liver oil use (HR = 1.6, 95% CI = 0.9-2.6).
      Smokers, regardless of their cod liver oil use were at a substantially higher
      risk for CHD mortality relative to non-smokers. Omega-3 fatty acid
      supplementation, as practiced in this cohort, provided no significant benefits to
      CHD risk among study participants.

PMID- 11507964
TI  - Moulds, moisture and microbial contamination of First Nations housing in British
      Columbia, Canada.
AB  - This paper reviews the difficulties experienced with mould growth in First
      Nations homes in British Columbia and to describe the team approach used in
      dealing with this problem. Humid, damp conditions promote the growth of bacteria,
      moulds, and dust mites. These organisms contribute to poor air quality and causes
      serious health problems. There is increasing evidence indicating an association
      between mould, particularly toxigenic moulds, and some diseases, notably asthma.
      These health problems usually improve when families are relocated to more
      suitable accommodation. Those particularly at risk include atopic,
      immunocompromised, very young and elderly individuals and those with chronic
      health conditions. Our experience suggests that substandard housing is a major
      contributor to poor health in First Nations communities.

PMID- 11507965
TI  - Exposure to persistent organochlorines among Alaska Native women.
AB  - OBJECTIVES: To report the levels of DDT, DDE, other chlorinated pesticides, and
      PCBs found in 131 Alaska Native women who had serum samples collected between
      1980 and 1987 and to compare these levels to other published studies of DDE and
      PCB exposure among U.S. women. STUDY DESIGN: Review of data collected during a
      case-control study of the relationship between organochlorine chemicals and
      breast cancer. Data for case and control women were pooled in this analysis
      because case-control differences were found to be minimal and because serum
      samples pre-dated cancer diagnoses by 3 to 10 years. RESULTS: More than 99% of
      the women had detectable levels of p,p-DDE (mean 9.10 ng/mL or ppb). Mean total
      PCB level was 7.56 ppb. Levels of exposure varied by geographical location and
      ethnic identification, which maybe a reflection of dietary differences. Five of
      the organochlorines were detected in at least half of the study population.
      Results were recalculated using detection limits corresponding to other published
      studies of DDE and PCB levels in U.S. women. Alaska women had levels similar to
      those reported from New York women collected in the 1980s. We compared the PCB
      congener levels measured in Alaska Native women with levels reported in Arctic
      animals and found similar PCB congener profiles. The six most frequently detected
      contaminants in Alaska Natives were also detected in the marine mammal samples
      reported by Becker et al (5). CONCLUSIONS: Our study identified widespread Alaska
      Native exposure to organochlorines that originated outside of the Arctic, a
      finding also seen in other studies. Our results provide a reference baseline for
      exposure levels during the 1980s, but further research is necessary to assess
      temporal trends in exposure among Alaska Natives. Further, the need for national
      and international inter-laboratory standardization for testing for persistent
      organochlorines to facilitate comparisons between Alaska Natives and other
      American populations is clearly demonstrated.

PMID- 11507966
TI  - Ecology and community health in the north.
AB  - Health of a nation is a sensitive barometer of the environmental situation,
      especially in the North, where vulnerable nature cannot resist intensive
      industrial development. The geographical location and severe climatic conditions
      of the Republic of Sakha (Yakutia) significantly sharpen any negative impact of
      industrial activity on the state of the environment. The impact of ecological
      factors on the health of population has been studied in the case of a diamond
      province (Vilyuy region), where a complex of chemical pollutants from diamond
      mining, products of wood decay in places of flooding of the water reservoir for
      the Vilyuisk power station, highly mineralised underground waters and
      consequences of underground explosions have caused a substantial negative effect
      on the environment and people. Studies on the health of the population in the
      Vilyuy region has shown that sickness and morbidity rates of viral hepatitis,
      tuberculosis, pathologies during pregnancy and other diseases are higher in
      comparison to rates in the Republic as a whole, a feature which has been
      attributed to environmental degradation in the area.

PMID- 11507967
TI  - Risk perceptions and First Nations communities.
AB  - When conducting research in First Nations communities problems can arise when
      applying research methods that were developed for Western society. Studies of
      environmental risk perception, the subfield of environmental risk assessment and
      management that incorporates the opinions and feelings of "lay persons" into the
      assessment process, are not immune to this. These studies of risk perception are
      generally based on statistical analyses derived from questionnaires. This paper
      will argue that the methodology used in studying the perception of risk of First
      Nations people should be culturally sensitive to the particular community that is
      being studied. This can be accomplished with direct community approval and
      cooperation from the initial decision on whether or not a study is needed, the
      research itself, and finally the communication of results. This paper is not
      meant to be a critique of the field of risk perception, but is instead a
      discussion of the characteristics of community-based research relevant to the
      field of risk perception.

PMID- 11507968
TI  - The epidemiology of injuries in Svalbard compared with Harstad.
AB  - STUDY OBJECTIVE: To survey all injuries treated in Longyearbyen hospital,
      Svalbard and to describe the injury epidemiology for Svalbard (residents and
      visitors), comparing it with Harstad. SETTING: The Norwegian arctic archipelago,
      Svalbard and the mainland city Harstad during three years from 8 March 1997.
      PARTICIPANTS: The person years of the study were 4211 for Svalbard residents and
      69,014 for Harstad. MEASUREMENTS AND MAIN RESULTS: The variables followed the
      Nordic system. Of 630 recorded injuries, 107 were snowmobile related. Crude
      injury rates (per 1000 person years) [corrected] for Svalbard residents were for
      men 100.9 and for women 76.3. Corresponding rates were not significantly higher
      for men in Harstad (115.4, p = 0.19) and for women (80.1, p = 0.56). Home
      injuries were more prevalent in Harstad (30.5%) compared to Svalbard residents
      (13.1%, p < 0.001) and visitors (8.9%, p < 0.001). Work and leisure related
      injuries were more prevalent for Svalbard visitors (38.8% and 48.7%) and
      residents (27.2% and 41.9%) compared to Harstad (13.2% and 34.8%) (both p <
      0.001). 43.5% of Svalbard visitors sustained work related injuries at sea. These
      injuries had higher AIS (abbreviated injury scale) mean score (1.83) than
      visitors' work injuries occurring on land (1.41) (p < 0.05) and residents' work
      injuries (1.29) (p < 0.001). Harstad had lowest AIS score for work related
      injuries (1.24). The violence rate (per 1000 person years) was 0.9 for Svalbard
      residents, less than a third of the Harstad rate (p < 0.02). There was one
      Svalbard resident fatality (drowning).

PMID- 11507969
TI  - Knowledgeable, consistent, competent care: meeting the challenges of delivering
      quality cancer care in remote northern communities.
AB  - The Northwestern Ontario Regional Cancer Centre (NWORCC) has created outreach
      services that provide chemotherapy and supportive care to clients in thirteen
      small, remote communities. Located 100-600 km from the NWORCC, these satellite
      oncology services are staffed by local physicians, specially prepared nurses and
      support staff. The present paper reports selected findings from an evaluation of
      the service, based on two rounds of site visits, interviews and surveys of
      providers and clients. Although the consensus was that quality care was being
      delivered, local hospitals and other organizations had to address a variety of
      challenges. Those discussed in the paper include: maintaining provider
      competency, strengthening supportive care networks, and adjusting staffing and
      other resources to meet increased demands for care.

PMID- 11507970
TI  - Prevalence of type 2 diabetes in northern populations of Siberia.
AB  - In the first part of the study the prevalence and incidence of diagnosed Type 2
      diabetes among adult rural populations of southern, central and northern areas of
      the Krasnoyarsk region of Siberia is compared. The six-year mean incidence of
      diabetes in the southern area was 0.86 per 1000 (95% CI: 0.66-1.06), in the
      central area this incidence was 0.79 (0.57-1.01). In contrast, in the northern
      area the mean Type 2 incidence among indigenous population was 0.16 per 1000 (0
      0.43) and among aliens it was 0.38 (0.22-0.54). The age-standardised Type 2
      diabetes prevalence in the population of southern and central areas were 10.23
      (9.55-10.-92) and 10.77 (9.99-11.55), respectively. In the northern area among
      aliens it was 8.98 (8.18-9.78) and among indigenous peoples only 2.54 per 1000
      (1.46-3.62). The second part of this study consists of a population based survey
      to determine the prevalence rate of Type 2 diabetes among 596 Evenks and 306
      alien inhabitants in Evenkia (82% eligible participants of Baikit district). No
      cases of glucose intolerance were found among Evenks in this study and one case
      of Type 2 diabetes was confirmed among aliens (prevalence rate 3.27 per 1000).
      These data indicate that Type 2 diabetes is still rare among northern indigenous
      populations of Siberia and that diabetes in northern alien populations is less
      prevalent than among peoples of central and southern areas of Siberia.

PMID- 11507971
TI  - Ten-year trends in cardiovascular risk factors of Siberian adolescents.
AB  - PURPOSE: To evaluate trends in CVD risk profile of adolescent population in
      Novosibirsk during social and economic crisis in Russia (1989-1999). DESIGN:
      Three cross-sectional surveys of samples of schoolchildren aged 14-17 in 1989
      (657), in 1994 (620) and in 1999 (626) were undertaken. Total sample was 1903
      (914 males and 989 females). The programme of the surveys included a
      questionnaire (smoking and physical activity habits), measuring blood pressure,
      weight, serum lipids and lipoproteins, and a 24-hour dietary recall. RESULTS:
      Prevalence of regular smoking (1 cig/day and more) decreased from 42% (1989) to
      33% (1999) in males. Frequency of overweight (BMI > = 22.0) significantly
      decreased both among boys (from 29% to 7%) and girls (from 30% to 14%). The
      number of teenagers with high blood pressure (systolic or diastolic BP > = 140/90
      mm Hg) also decreased in both gender groups. The prevalence of high total
      cholesterol (> = 200 mg/dl) significantly decreased from 22% to 6% in males and
      from 32% to 14% in females. The frequency of low HDL cholesterol (< = 40 mg/dl)
      also decreased in boys (from 28 to 8%) and girls (from 12.5% to 3%). Low physical
      activity (< = 2 h/week) was high and without any big changes. CONCLUSIONS: The
      results obtained showed serious changes in the CVD risk profile of Siberian
      adolescents during the crisis period.

PMID- 11507972
TI  - Plasma lipoprotein (a) levels and Apo(a) isoforms in native population of
      Chukotka with and without arterial hypertension.
AB  - Lipoprotein(a) (Lp(a)) levels and Apolipoprotien(a) (Apo(a)) isoforms in blood
      plasma were determined among the native population of Chukotka (Chukchee, Eskimo)
      in 32 persons with and 148 persons without Arterial Hypertension (AH). Plasma
      Lp(a) levels were determined by radial immunodiffusion using polyclonal
      antibodies raised against purified Lp(a) human plasma. The range of fluctuations
      of Lp(a) levels was wide: 0-77 mg/dl (Chukchee), 0-48 mg/dl (Eskimo). The
      distribution in the total population was also highly skewed, yielding a curve
      similar to a negative exponential function. Insignificant differences were found
      in the levels of Lp(a) between persons with and without AH: 22.9 +/- 2.6 vs. 20.6
      +/- 0.8 mg/dl. Apo(a) isoform S4 as homozygous appears to be more frequent in
      patients with AH (8.1%), than in persons without AH (15.3%), isoform S2 in 30.2%
      and 19.2%, isoform S1 in 3.9% and 2.9%, respectively (in all cases p > 0.05). In
      conclusion, plasma Lp(a) levels in native population of Chukotka (Chukchee,
      Eskimo) did not differ between persons with AH and without AH. Apo(a) isoform
      distribution differed slightly between Chukchee and Eskimo with AH and without
      AH.

PMID- 11507973
TI  - The estimation of gametic disequilibrium between DNA markers in candidate genes
      for coronary artery disease (CAD) and the associations of gene complexes with
      risk factors for CAD.
AB  - In this investigation associations of gene complexes consisting of seven
      candidate for coronary atherosclerosis (ACE, AGT, NOS3, APOA1, MTHFR, PLAT, F13)
      with risk factors for CAD (lipid levels, blood pressure, body mass index (BMI))
      were studied in Russian population. 94 male patients with CAD proven by
      angiography and 131 healthy individuals were involved in the case-control study.
      We observed a significant contribution of gene combinations ("ensembles"). ACE
      MTHFR, ACE-F13, ACE-AGT-MTHFR in the variability of the total cholesterol and LDL
      cholesterol levels. The "Ensembles" ACE-AGT-MTHFR were associated with
      variability of three atherogenic risk factors (LDL, BMI, cholesterol total). Two
      locus gametic disequilibrium was analysed between gene polymorphisms. NOS3 and
      ACE, NOS3 and APOA1 were in gametic disequilibrium in the control group.
      Polymorphic markers of ACE and F13, NOS3 and F13, ACE and PLAT loci were in
      gametic disequilibrium in the patients. Both approaches (association analysis and
      gametic disequilibrium) revealed the same gene combinations contributing to the
      CAD risk factors. NOS3 and APOA1 markers were in gametic disequilibrium in the
      patients and both of them were associated with LDL. F13 and AGT were associated
      with systolic and diastolic blood pressure and two-locus gametic disequilibrium
      between F13 and AGT polymorphisms observed in the patients.

PMID- 11507974
TI  - Genetic polymorphisms of CYP1A1, GSTM1 and P53 genes in a unique Siberian
      population of Tundra Nentsi and its pharmacogenetic importance.
AB  - Complete data on the polymorphisms of CYP1A1, GSTM1 and p53 genes in Tundra
      Nentsi population, with known genealogical history are essential for the analysis
      of the "cancer susceptibility gene markers" distribution among different Oriental
      populations. The cytochrome P4501A subfamily is known to be responsible for the
      metabolic activation of aromatic compounds occurring in the products of gas
      mixture combustion, the main environmental pollutants in the north of western
      Siberia. Recently a close correlation was reported between development of some
      types of cancer and polymorphisms of human CYP1A1, GSTM1 and p53 genes. The
      frequency of the CYP1A1 Vol allele in the healthy part of the Tundra Nentsi
      population differs from those previously reported for Japanese and is more than
      1.5 times higher. It is necessary to underline that homozygote Val genotype was
      present in 26% of non-healthy Tundra Nentsi, the incidence being 2.7-times higher
      in comparison with healthy population. GSTM1 gene deletion is present in 40% of
      Orientals and in 39% of Tundra Nentsi. Moreover, the share of individuals with
      null genotype among a group with chromosomal abnormalities and cancer was 63%, or
      1.5 fold higher. Thus the prevalence of two polymorphic genes CYP1A1 and GSTM1
      responsible for the biotransformation of polycyclic aromatic hydrocarbons was too
      high in the non-healthy group.

PMID- 11507976
TI  - Pulmonary tuberculosis in Yakutsk at the end of the 20th century.
AB  - The objective of the study is to identify the share of lethality from pulmonary
      tuberculosis and its nature over the last decade in Yakutsk. The study is based
      on the analysis of 98 autopsies of adults who died from a variety of infectious
      diseases during 1993-1995. The study shows that the proportion of lethal outcomes
      from tuberculosis is high and comprises 63.3% out of other infectious diseases.
      The nature of the lethality is characterized by the death of adults mainly from
      20 to 50 years old and totals 67.8%. 67.7% of the lethal outcomes are caused by
      the fibrous-cavitary form and 19.4% by the disseminated pulmonary form of
      tuberculosis.

PMID- 11507975
TI  - Short-term functional outcome of hospitalised first-ever strokes in Finnmark,
      Norway in 1998-1999. Results from the Finnmark Stroke Register.
AB  - Data on the functional outcome, prevalence of risk factors and comorbidity of
      stroke were collected in the population-based Finnmark Stroke Register in
      northern Norway. Findings for hospitalised first-ever strokes (n = 125) during
      the first registration year (1998-1999) are presented here. The median age of the
      patients was 70 years for men and 79 years for women. Cerebral infarctions
      comprised 81.6% of the strokes. Patients were severely handicapped: at discharge
      from hospital about 46% of those 75 years or older and about 21% of those younger
      than 75 years had severe disability by Rankin Scale. Women were more impaired
      than men. After hospitalisation, 45% of those 75 years or older and 21% of those
      younger than 75 years were sent to nursing home. The prevalence of risk factors
      and comorbidity was high: 29% of men (52% of women) had high blood pressure, 22%
      of men (25% of women) had atrial fibrillation, 22% of both men and women had
      diabetes, and 50% of men and 33% of women were current smokers. In conclusion,
      stroke victims in Finnmark were left with severe disability and need intensive
      rehabilitation. The prevalence of treatable risk factors was high; thus, primary
      and secondary prevention is the key to reduce the individual and social burden of
      stroke.

PMID- 11507977
TI  - Prevalence of Helicobacter pylori infection in the Asian part of Russia.
AB  - The purpose of the present study was to evaluate the prevalence of H. pylori
      infection in various regions of Siberia and the Far East. A representative sample
      of adult Novosibirsk population participated in the study and four groups of
      native population of various regions of Siberia were examined, and patients' sera
      were tested using ELISA. H. pylori is widespread among Siberian populations with
      prevalence rates ranging between 71% and 92%. Almost maximum prevalence rates of
      H. pylori infection occurred by the age of 30 years, with only minor increase at
      older ages.

PMID- 11507978
TI  - Prevalence of dyspepsia and irritable bowel syndrome among adolescents of
      Novosibirsk, western Siberia.
AB  - The study was undertaken to determine the prevalence of gastrointestinal symptoms
      in a community-based population of adolescents. All students in grades 9-11 of
      four randomly chosen schools in one of the typical districts of Novosibirsk were
      invited to participate. A total of 449 students participated (189 boys, 260 girls
      aged 14-17), all of them completed the Russian version of the Bowel Disease
      Questionnaire. Dyspepsia was reported more frequently by girls than boys (27% vs
      16%). The prevalence of irritable bowel syndrome defined according to the Rome
      criteria was 24% in girls and 14% in boys. Among students with dyspepsia, 49% had
      sought medical advice, and 37% had undergone upper gastrointestinal endoscopy or
      X-ray series, for IBS the corresponding figures were 49% and 24%. School
      absenteeism was reported by 57% of dyspepsia sufferers, and by 62% of subjects
      with IBS. In conclusion, dyspepsia and IBS are common among adolescents of
      Novosibirsk with prevalence rates similar to those described in adults in Western
      Europe and the USA. These disorders are associated with significant disability
      and health care costs.

PMID- 11507979
TI  - Immunogenetic factors of predisposition to duodenal ulcer in Caucasian population
      of western Siberia.
AB  - A total of 47 Caucasian duodenal ulcer patients and 680 healthy persons were
      investigated for HLA antigens of classes I and II. HLA antigens of the A, B
      series were sought using the microlymphocytotoxicity test, and HLA-DRBI was
      analysed by polymerase chain reaction. The study found associations of duodenal
      ulcer with HLA-A10, -B41 and different combinations of these alleles, whereas HLA
      A9 was found to be protective. A relative risk of peptic ulcer was 3.03 in HLA
      A10 (pcor < 0.05), and 7.78 in HLA-B41 (p < 0.001). The allele frequency A9 was
      higher in healthy controls (30.15%) than in Helicobacter pylori-positive patients
      with duodenal ulcer (10.64%, RR = 3.50, pcor < 0.05). The study showed that
      frequencies of alleles HLA-DR7 and HLA-A1/B12 were higher in Helicobacter pylori
      positive duodenal ulcer patients with family history of peptic ulcer (RR = 4.00
      and RR = 11.92, respectively p < 0.05). These data suggest that HLA may influence
      duodenal ulcer susceptibility and resistance, and according to the high
      prevalence of Helicobacter pylori (HP) infection in Siberian population (87.5%),
      this may occur through a non-HP infection pathway.

PMID- 11507980
TI  - Diffuse liver lesions among the general population of western Siberia.
AB  - The study was aimed at ascertaining the prevalence of diffuse liver lesions and
      associated factors in the general population of Novosibirsk, Western Siberia. A
      representative sample of 362 men and 870 women aged 25-64 years was investigated
      using ultrasound examination and blood tests for liver-derived enzymes (AST, ALT,
      GGT). Diffuse liver lesions (DLL) were detected in 42.8% of males and 18.7% of
      females. A significant association was found between DLL and elevated levels of
      liver enzymes. In conclusion, the prevalence of chronic liver disease is
      relatively frequent in the unselected urban population.

PMID- 11507981
TI  - Socio-economic and school factors of psychological and physical health in
      Siberian schoolchildren.
AB  - Cultural influences on psychological and physical health were examined in a
      sample of Russian schoolchildren in Novosibirsk. To evaluate the children's
      behaviour the translated short form of the Child Behaviour Checklist was given
      out to mothers. A School Adjustment Scale and the Rutter Teacher Questionnaire
      were completed by teachers and one total score was derived from the Rutter Health
      Questionnaire for children. Children from disturbed families had worse school
      adjustment and more behavioural problems. Acute respiratory diseases were more
      frequent in children from large families, while the mother's education level was
      a protective factor. Academic attainment was positively related to parents'
      education, CBCL Somatic Complaints and the occurrence of psychosomatic and
      inflammatory diseases, and negatively related to Externalising Problems. The CBCL
      Somatic complaints score was the key variable in the prediction of most physical
      health variables. Overall, the findings show the significance of academic
      attainment for a child's physical and psychological health. Low academic
      attainment tends to be connected with Externalising Problems, while higher
      attainment could be connected with somatisation and physical illness.

PMID- 11507982
TI  - Culture-bound mental disorders among the Tatars of the Siberian north.
AB  - Several forms of culture-bound mental disorders and their shamanic treatment
      among the Tatars of North Siberia were studied: kizil kootalak--possession by the
      Spirit of Fertility; orak--moving in of the Spirit of Suicides; oolamchak--the
      disorder of the natural exchange between the inner and the outer Spirits that
      induces depression with lethal exit. The shamanic treatment included specific
      rituals where the shaman receives the support of helper Spirits and the Spirit of
      the Great Shaman. Misunderstandings concerning terms and concepts of culture
      bound states are analysed.

PMID- 11507983
TI  - Suicide in a society in transition.
AB  - In Greenland, the rapid socio-cultural change of the last 50 years has been
      paralleled by an increasing number of suicides. The suicide rates in Greenland
      are now among the highest in the world. Especially among men aged 15-24 suicide
      rates are dramatically high. In the present study, information on the psycho
      social background of suicides is provided based on a review of death certificates
      and police reports for the period 1993-95. Dysfunctional social networks seem to
      play a predominant role among suicides. Being disconnected from community and
      family ties seems to increase the vulnerability of young people in Greenland. In
      addition, temporal trends of suicide rates are described for the different
      regions of Greenland. The findings are discussed in relation to the societal and
      cultural transition of the society.

PMID- 11507984
TI  - Acute phase proteins as biological markers of addictive disorders in teenagers
      and children.
AB  - Acute phase proteins (APP), including C-reactive protein (CRP), alpha-1
      proteinase inhibitor (PI) activity and albumin level were studied in serum of 183
      teenagers and children with drug addictive disorders (DAD) (mainly home-made
      opiate dependence and glue-sniffing), hospitalised at Municipal Drug Addictive
      Centre, Novosibirsk (1996-1999). Serum CRP concentration increased several times
      during early withdrawal period in the teenager group with opiate dependence. In
      most cases of DAD decreased level of albumin (negative APP reactant) as well as
      decreased activity of PI was revealed. After treatment (about 21 days after onset
      of hospitalisation) the level of albumin still remained decreased. These indexes
      were suggested as a possible surrogate biological marker of DAD, and immune
      stimulators were recommended during DAD treatment to restore the decreased level
      of protective APP of these patients.

PMID- 11507985
TI  - The quality world change as a cause of addiction development in conditions of the
      north.
AB  - OBJECTIVE: The aim was to study the quality world (QW), according to Glasser, in
      newcomers to the North. METHOD: The study included clinical examination of
      newcomers to the North according to DSM-IV criteria. The QW was studies defined
      as important figures of significant others (parents, family members, persons
      loved, friends, acquaintances etc.) with various functions, such as control,
      revision, support and others. RESULTS: It was found in the newcomers of North
      that they were unable to structure time in the way typical of their previous
      life, and that the absence of outside control from the significant others was
      expressed. The clinical evaluation revealed a strong sense of discomfort,
      anxiety, and depression. It was typical of the newcomers that they often tried to
      escape these feelings by alcohol intake, The newcomers used alcohol as a remedy
      to stimulate the imagination and to overcome the barriers in interpersonal
      relationships in the new environmental conditions. Alcohol also helped to re
      establish the former patterns of self-object relationships and to re-experience
      the feelings of the comfortable QW pattern. The obtained data revealed that
      social isolation and hypostimulation led to a faster development of psychological
      alcohol dependence.

PMID- 11507986
TI  - Antismoking activity in Novosibirsk.
AB  - The prevalence of smoking is very high and growing in Siberia. Three population
      surveys carried out by the Institute of Internal medicine within the framework of
      the MONICA project (WHO) during 1988-1995 revealed that 59% of the men and 11% of
      the women aged 25-64 are smokers (2). The number of smokers among children is
      also growing: 21% of girls and 40% of boys aged 14-17 are smokers (1). Tobacco
      product advertising is widespread in the city. Cheap cigarettes of bad quality
      are easily available for the population. The economic situation in the region
      makes it difficult for people to pay for specialised treatment. That is why new
      methods of smoking prevention should be found. The main components of our work
      are: involving local decision-makers in the activity, educating the population,
      work with mass media, epidemiological studies, international Quit & Win
      campaigns.

PMID- 11507987
TI  - Body thermal state influence on local skin thermosensitivity.
AB  - Three series of experiments (I-III) on 33 volunteers aged 20-23 years old were
      carried out using the climatic chamber. The thermal thresholds were measured on
      the forearm of men dressed only in swimming trunks. The Peltier thermode was
      used. Inspection I was carried out in a thermoneutral environment (27 degrees C)
      with 1 degree C step modification of the initial thermode temperature ("i) within
      29-38 degrees C temperature span. In an alternative experiments (II) the "i was
      supported at 33 degrees C, while the men were exposed to 20, 27 and 38 degrees C.
      In the last series (III) "i was maintained close to natural cutaneous temperature
      and the environmental temperatures were 27, 20 and 14 degrees C. It is shown that
      selected changes of local cutaneous temperature (I series) or the medium
      temperature (II series) render the a sharply expressed and opposite influence on
      local thermal thresholds. Common body cooling (III series) also reduces local
      thermal sensitivity. The equations and three-dimensional graphs linking
      thresholds of local thermal sensitivity, local skin temperature and average
      weighted full coverlet temperature (or deep body, or environmental temperature)
      on obtained data were computed. They allow taking into account the influence of
      body thermal state in practice of a quantitative cutaneous thermal sensitivity
      definition.

PMID- 11507988
TI  - Ten-day cold exposures develop adaptation-compensatory mechanisms of regulation
      of heat exchange and breathing.
AB  - The purpose of the study was to determine types of general cold adaptation and to
      reveal adaptation-compensatory regulation mechanisms of heat exchange and
      breathing. 24 healthy subjects were tested. Thermoregulation and gas exchange was
      measured before, during and after a 10-day cold exposure (13 degrees C, 2 h).
      Before and after cold exposures the ventilatory CO2 and O2 sensitivity was
      measured by the rebreathing method. The gas-analyser Eos Sprint ("Erich Jaeger",
      Germany) was used. The whole group exhibited the hypothermic isoinsulative
      adaptation type: during cold exposure Tre decreased (P < 0.01), Tsk did not
      change, the delay for the onset of shivering increased (P < 0.001), Tre of the
      onset of shivering decreased (P < 0.01). According to Tre measured at 120 min of
      the 10th day the group was divided in two. In the first group the adaptive
      response was based on thermoregulation changes only. In the second group adaptive
      response was based on both thermoregulation changes and breathing regulation
      changes: ventilatory CO2 and O2 sensitivity increased (P < 0.01), the
      oxyhaemoglobin dissociation curve moved to the right (P < 0.01). Thus we can
      propose that subjects of the first group will be more successful in cold
      adaptation, whereas the second group will be unsuccessful in cold adaptation and
      at risk for respiratory diseases.

PMID- 11507989
TI  - Problems of combined chronic pathology in newcomers of the north.
AB  - The problem of a combination of diseases is of great in the clinical treatment of
      internal diseases. Syntropy is of great significance to the northern population.
      A total of 617 patients living in Yakutia were studied. Analysing the combination
      of chronic pathology by means of the international classification of diseases was
      revealed that 7.4% of patients have only one nosological form and 55.1% had been
      diagnosed with 5 and more nosologies. When analysing the combination of the
      classes of the international classification of diseases it was seen that patients
      with one class constituted 14.0%. At same time the number of classes of the
      diagnosed pathology comprised 3 and more in 44.3% of the patients. In our opinion
      the process of long human adaptation to severe climatic conditions leads to a
      decrease of the functional reserves in an organism and disadaptation in
      newcomers. It leads to the development of severe chronic polynosological
      pathology, pathogenesis of which is defined by the for need complex of
      disadaptive disorder.

PMID- 11507990
TI  - Northern cardiometeopathies.
AB  - Our research in high latitudes has allowed the identification of a special class
      of deadaptive disorders, northern cardiometeopathies, which integrates
      cardiovascular functional violations connected to biologically significant
      modifications of meteorological, geomagnetic, electrical, gravitational,
      rhythmological and other geo-ecological factors of the North. Cardiac and
      cerebral disorder complexes, and also some psychoemotional modifications manifest
      cardiometeopathies. Cardiometeopathies can occur with developing of pathology,
      and in such a case they can be selected in the independent form of deadaptive
      disease. At the same time, cardiometeopathies in case where cardiovascular
      pathology already exists could cause complications and become a particular risk
      factor for the development of injuries and myocardial heart attack. The most
      important mechanism of cardiometeopathies' formation is the organism's reaction
      to modifications of the Earth's electromagnetic field, based on internal
      electromagnetic fields' (first of all pulsing field of heart) dependence on the
      magnitude and directness of modification of the external electromagnetic fields.
      The analysis of the high degree of dependence of the blood circulation effiency
      during geomagnetic perturbations in the North of the modification of
      electromagnetic heart activity allows us to speak of the discovery of an earlier
      unknown electromagnetic blood pump.

PMID- 11507991
TI  - Seasonal variations in respiratory system in healthy inhabitants of west Siberia.
AB  - The aim of this work was to investigate seasonal variations in oxygen
      consumption, ventilation, lung volumes and their relationships in healthy adult
      inhabitants of West Siberia. The investigations were performed in Novosibirsk.
      Thirty healthy male adult volunteers were studied 4 times during a year: in
      summer (mean monthly temperature +20 degrees C), autumn (+2 degrees C), winter (
      18 degrees C), and spring (degrees C) under the same conditions in a room at
      rest. Oxyspirography, pneumotachography and the helium dilution method were used.
      Oxygen consumption (VO2), breathing frequency, vital capacity (VC) and
      inspiratory capacity were adjusted to be the same during the year. Minute
      ventilation (Ve), VO2-Ve ratio, residual volume (RV) and expiratory reserve
      volume (ERV) to RV ratio had dynamics concurrent with seasonal temperature
      dynamics. Tidal volume, ERV, functional residual capacity, forced 1-s expired
      volume (FEV1) and FEV1/VC also changed, but their dynamics were different from
      the previous parameters. The minimum value of these parameters was found in the
      spring and the maximum--in the autumn, or summer and autumn. Correlations between
      respiratory parameters also changed during the year. We conclude that oxygen
      consumption is provided by reorganisation of pulmonary tissue in winter.

PMID- 11507992
TI  - Differences in self-disclosure in psychotherapy between American and Israeli
      patients.
AB  - This study investigated differences in extent and patterns of disclosure in
      psychotherapy between American (n = 164) and Israeli (n = 45) patients.
      Participants completed the Disclosure to Therapist Inventory-R, an 80-item
      measure that uses a rating scale to assess the extent to which psychotherapy
      patients have discussed each of 80 moderately to highly intimate topics with
      their most recent therapist. Analysis yielded no significant difference between
      groups in overall disclosure and high overlap in the topics most and least
      discussed. Both groups frequently discussed aspects of their personalities they
      disliked, feelings of desperation or depression, and feelings of rage or anger
      towards parents. Findings suggest universal concerns may outweigh the cultural
      context in which therapy occurs.

PMID- 11507993
TI  - Effects of permanent residence with foster mothers and new siblings upon numbers
      of mast cells within the thalamus of preweaned rats.
AB  - In a split-litter, cross-fostered design, the numbers of mast cells per 10
      micrometer sections within the thalamic boundaries in rats that had been reared
      by 8 natural or 8 foster mothers were counted 5 days and 10 days after the
      transfer had occurred on postnatal Day 10. The rats from 4 litters with the
      highest numbers of thalamic mast cells exhibited marked reductions in these
      numbers when fostered by mothers of the 4 litters with the fewest numbers of
      thalamic mast cells. The reverse influence was not observed. These results
      suggest that adaptation to changing maternal environments for rats with
      congenitally elevated numbers of mast cells may increase the risk of
      degranulation and transient anomalies within cerebral vasculature or the blood
      brain barrier.

PMID- 11507994
TI  - Organizational factors as predictors of teachers' burnout.
AB  - The purpose of this study was to examine the burnout experienced by a sample of
      Greek teachers and to explore the extent to which certain organizational factors
      predict teachers' scores on the Maslach Burnout Inventory. The sample consisted
      of 100 teachers, 28 to 59 years of age. Greek teachers' means were lower than
      those for burnout of U.S. teachers. Stepwise regression analysis identified
      satisfaction with the job itself was the only significant predictor for
      Depersonalization and Emotional Exhaustion subscales, while satisfaction with the
      job itself and satisfaction with promotion were significant predictors for the
      Personal Accomplishment subscale. These findings showed that stress, e.g., role
      conflict and role ambiguity, were not highly correlated with teachers' burnout.

PMID- 11507995
TI  - Relationship between exposure to community violence and psychological distress:
      linear or curvilinear?
AB  - This paper presents data testing the hypothesis that the relationship between
      exposure to recurring community violence during high school years and later
      experiencing of psychological distress symptoms is a quadratic curvilinear one.
      Data were collected between 1994-1996 by self-administered questionnaires using
      multi-item scales; the sample (N = 452) comprises older urban adolescents.
      Although exposure to community violence was positively and linearly related to
      psychological distress, no statistically significant quadratic curvilinear
      relationship was found between community violence and psychological distress.

PMID- 11507996
TI  - Objective measurement of paranormal belief: a rebuttal to Vitulli.
AB  - Effects of age and sex in paranormal belief remain controversial because issues
      of scaling and differential item function are not given due attention. Therefore,
      in response to the recent debate between Irwin and Vitulli, these issues are
      reviewed and validated as crucial approaches for obtaining an objective measure
      of paranormal belief. A Rasch version of Tobacyk's Paranormal Belief Scale has
      been developed, but research with this scale suggests that--contrary to past
      literature and recently refined studies--age and sex are neither consistent nor
      crucial factors mediating paranormal belief.

PMID- 11507997
TI  - A proposed method for learning from textbooks in the primary grades: use of text
      structure to guide self-questioning.
AB  - A questioning strategy is proposed for teaching primary-level children about text
      organization or structure, such as cause-effect, comparison-contrast, and problem
      solution. Once students can reliably identify different types of organization,
      they are taught to ask questions appropriate to each type to guide their
      learning. A cognitive-strategy instruction model is used as the vehicle for
      teaching children through modeling by a teacher, interactive discussion, and
      practice with corrective feedback. In addition, students are taught how to
      monitor the process, so responsibility is transferred from teacher to student.
      Some questions demand searching for answers in the text. Others are more complex,
      demanding integration of textual elements and use of personal knowledge for
      answering questions.

PMID- 11507998
TI  - Spirituality in late adulthood.
AB  - MacDonald's Expressions of Spirituality Inventory was used to examine
      spirituality in late adulthood using a sample of 30 people (22 women, 8 men)
      whose mean age was 72.6 yr. While average scores are higher on scales measuring
      spiritual and religious beliefs and practices for the sample than for a
      standardization group of undergraduate students with a mean age of 21.0 yr.,
      means are lower on scales measuring paranormal beliefs. Low scores on death
      anxiety are correlated only with Existential Well-being and age. And, while some
      religious behaviors such as frequent religious practice, prayer, and church
      attendance are correlated with some of the dimensions of spirituality, many of
      the scores on the Expressions of Spirituality Inventory scales are independent of
      self-reported religious behaviors.

PMID- 11507999
TI  - Silencing the self and the big five: a personological profile of silent women.
AB  - This study examined the correlations between scores on Jack and Dill's 1992
      Silencing the Self Scale and Costa and McCrae's 1985 Big Five personality factors
      among 146 female undergraduates. Analyses indicated the Silencing the Self scores
      were positively correlated with those on Neuroticism and negatively correlated
      with those on Openness, Extraversion, and Agreeableness. In addition, regression
      analysis indicated that Neuroticism and Openness scores showed the greatest
      contribution to Silencing the Self scores. These findings suggest the possible
      importance of studying personality traits in women who utilize the silencing the
      self schema in interpersonal contexts.

PMID- 11508000
TI  - Stepping aside for elderly persons in American versus east-Asian cultures.
AB  - In the current study, younger (15-30 years of age) and older (60+ years of age)
      Asian-American and European-American individuals (N = 160) were observed as they
      approached someone of the same ethnic group on a walkway at a city market. The
      interaction was recorded if one stepped aside and let the other pass. Younger
      Asian-Americans tended to step aside for older Asian-Americans. No such trend was
      observed among European-Americans. Results were discussed in terms of cultural
      values.

PMID- 11508001
TI  - Roles of outcome expectations and self-efficacy in preschoolers' aggression.
AB  - The present study examined preschool boys' beliefs for the outcome of aggression
      and their perceptions of self-efficacy for aggressive behaviors. 23 preschoolers
      (mean age 6.3 yr.; 12 aggressive boys and 11 nonaggressive boys) were presented
      stories about provocative situations and asked about three expectations for
      aggression: positive outcomes, peer rejection, and morality. Another 18
      preschoolers (mean age 6.3 yr.; 9 aggressive boys and 9 nonaggressive boys) rated
      their self-efficacy for four strategies: aggression, verbal persuasion, seeking
      help from a teacher, and withdrawal. Aggressive preschoolers did not expect a
      negative outcome in the form of peer-rejection in response to aggression as much
      as nonaggressive boys, although the groups did not differ in their expectations
      of positive outcomes and morality. Also, aggressive preschoolers were more
      confident about aggression in situations including teasing or criticism but less
      confident about verbal persuasion than nonaggressive preschoolers.

PMID- 11508002
TI  - Correlates of the impostor phenomenon among undergraduate entrepreneurs.
AB  - The impostor phenomenon describes the self-attribution of success to luck and
      interpersonal skills rather than to intelligence and ability, despite external
      validation to the contrary. Evidence suggests the presence of impostor
      characteristics among a group of 63 undergraduate entrepreneurs. More intense
      impostor feelings were associated with an external locus of control and a
      stronger perceived effect of work on family life. Implications for
      entrepreneurial performance are discussed and questions for research are
      presented.

PMID- 11508003
TI  - Sources of increasing agedness of references in psychology-of-learning textbooks,
      1952-1995.
AB  - This article identifies sources of a significant increase in the agedness of
      references in 89 learning textbooks published from 1952 through 1995.

PMID- 11508004
TI  - Gender perception of professional occupations.
AB  - Students (181 women and 44 men in a southern university) were asked to indicate
      their perception of whether each of 105 professional occupations was
      predominately masculine or feminine. Analysis indicated that a majority of the
      occupations were perceived as masculine, i.e., those predominately power- or
      product-oriented, while feminine occupations were predominately caregiving.
      Results were discussed in terms of the influence of media on the perception of
      gender-specific roles and the implications of these perceptions for the status of
      a person holding a given occupation.

PMID- 11508005
TI  - Preliminary data on the Multidimensional Fatigue Inventory-20 from female
      caregivers of male hemodialysis patients.
AB  - To test the reliability and concurrent validity of the Multidimensional Fatigue
      Inventory-20, 45 spouses or first-degree female caregivers of male hemodialysis
      patients in northern and eastern Iowa were administered the Multidimensional
      Fatigue Inventory-20 and the Rhoten Fatigue Scale. Four of the five subscales had
      a high Cronbach alpha (.76 to .82). There were low to moderate statistically
      significant Pearson correlations between scores on the Rhoten Fatigue Inventory
      and the MFI-20 subscales (.40 to .72). Limitations of generalizations are
      addressed.

PMID- 11508006
TI  - Self-confidence in financial analysis: a study of younger and older male
      professional analysts.
AB  - Measures of reported self-confidence in performing financial analysis by 59
      professional male analysts, 31 born between 1946 and 1964 and 28 born between
      1965 and 1976, were investigated and reported. Self-confidence in one's ability
      is important in the securities industry because it affects recommendations and
      decisions to buy, sell, and hold securities. The respondents analyzed a set of
      multiyear corporate financial statements and reported their self-confidence in
      six separate financial areas. Data from the 59 male financial analysts were
      tallied and analyzed using both univariate and multivariate statistical tests.
      Rated self-confidence was not significantly different for the younger and the
      older men. These results are not consistent with a similar prior study of female
      analysts in which younger women showed significantly higher self-confidence than
      older women.

PMID- 11508007
TI  - Answering two criticisms of hypothesis testing: reply to Serlin.
AB  - Two criticisms of hypothesis testing have been repeated for half a century.
      Leventhal (1999) defended against those criticisms. Serlin (2000) commented on
      Leventhal's paper and criticized parts of Leventhal's defense. Serlin's comments
      are discussed and his criticisms answered.

PMID- 11508008
TI  - Meaning in life and sense of mastery in Chinese adolescents with economic
      disadvantage.
AB  - Data from 229 Hong Kong Chinese adolescents with economic disadvantage showed
      that there was a positive relationship between reported meaning in life and sense
      of mastery.

PMID- 11508009
TI  - Validation of the Crisis in Family Systems-Revised, a contemporary measure of
      life stressors.
AB  - The objectives of this study were to establish the validity of the Crisis in
      Family Systems-Revised, a recently developed measure of contemporary life
      stressors, using the same validation technique as in the original validation and
      to provide further evidence of construct validity by assessing its relationship
      to socioeconomic status and residential location. We conducted 124 in-person
      interviews with parents in three outpatient pediatric asthma clinics affiliated
      with an academic medical center. The design was cross-sectional and
      correlational. Total count of life stressors accounted for 19% of the variance in
      scores on the Center for Epidemiologic Studies-Depression. Respondents using
      Medicaid and living in the city experienced more objective stressors, but the
      proportions of stressors rated as negative or positive (Valence), and ongoing
      (Chronicity) were fairly constant across subsamples, as was the Difficulty
      rating. Psychologists and health and mental health services researchers are in
      need of constructs relevant to contemporary society and its issues and tools to
      measure these constructs. Life stressors appears to be such a construct and the
      Crisis in Family Systems-Revised a measure with considerable utility.

PMID- 11508010
TI  - Depression and blood types.
AB  - A sample of 108 normal volunteers (grouped as blood Types O, A, and B/AB) were
      administered the Beck Depression Inventory. The results suggest that the
      association between depression and blood Type O that has been found for
      hospitalized patients can also be observed in normal patients.

PMID- 11508011
TI  - Depression, anxiety, and hopelessness in sexually abused adolescent girls.
AB  - 50 sexually abused girls showed significantly higher scores on depression,
      anxiety, and hopelessness than 50 nonabused controls. The 31 subjects who were
      repeatedly abused showed higher distress than the 19 abused ones. The results are
      discussed in the context of psychological dynamics, suicidal risk, and the need
      for intervention.

PMID- 11508012
TI  - Relations of imagery, creativity, and socioeconomic status with performance on a
      stock-market E-trading game.
AB  - The purpose of the present investigation was to examine how measures of imagery,
      creativity, and socioeconomic status relate to performance in a stock-market
      trading game. The 368 participants were students enrolled in an administration
      studies curriculum. A multiple regression analysis showed imaging scores to be a
      predictor of stock-trading performance as were creativity and socioeconomic
      status to a lesser extent. High imagers and high scorers on creativity and
      socioeconomic status made several times more profit with their portfolios.
      Results are discussed in terms of imagery having multiple repercussions on
      learning, e.g., memory and problem-solving. It is concluded that scores on
      imagery, creativity, and socioeconomic status, being weakly correlated, are
      interdependent and likely associated with personality traits shaped within a
      stimulating home or social environment.

PMID- 11508013
TI  - Height, societal threat, and the victory margin in presidential elections (1824
      1992).
AB  - Based on the idea that height serves as a heuristic for judgments about status,
      dominance, and leadership potential, two hypotheses were tested: (1) Heights of
      U.S. presidential election winners are positively correlated with estimates of
      social, economic, and political threat in election years. (2) Height and victory
      margin are positively correlated regardless of the magnitude of estimates of
      social, economic, and political threat in election years. Both hypotheses were
      supported for the 43 elections from 1824 to 1992.

PMID- 11508014
TI  - Diagnostic reliability and accuracy of pathological grief and psychiatric
      disorders among Japanese psychologists and psychology students.
AB  - The present study examined the reliability and accuracy of diagnoses regarding
      pathological grief and other psychiatric disorders using a case vignette design.
      Two Japanese psychologists (Ph.D. and M.A. levels) and five graduate students in
      psychology participated. Analysis suggests that psychologists and psychology
      students can reliably apply the diagnostic criteria for pathological grief and
      other psychiatric disorders.

PMID- 11508015
TI  - Correlations between cognitive style and performance on the water-level task by
      female graduate students.
AB  - The present study examined the correlation between cognitive style measured by
      the Group Embedded Figures Test and performance on two water-level tasks by 16
      female graduate students. The mean of the absolute deviation from the horizontal
      was used as the water-level task performance. As predicted, rho was -.49. Greater
      deviation on the water-level task was associated with low scores on the Group
      Embedded Figures Test, indicating field dependence.

PMID- 11508016
TI  - A preliminary study of proposed levels of relatedness in identity exploration
      among female late adolescents in Japan.
AB  - This study examined features of identity exploration among late adolescent
      Japanese girls from the viewpoint of relatedness. The expanded Ego Identity
      Interview was administered to 33 female university students. Five levels of
      relatedness were formulated in a sequence from exploration without relatedness to
      exploration with disagreements between one's own and others' perspectives. The
      results support the current view of researchers emphasizing relational aspects of
      identity and provide detailed features of the identity formation process from the
      viewpoint of relatedness among late adolescent girls in Japan.

PMID- 11508017
TI  - Stress, coping, and success among graduate students in clinical psychology.
AB  - Research has indicated that coping styles and social support are moderating
      variables in the relationship between stress and distress. Few studies, however,
      have examined the relationship between these variables and the relative health
      and success of graduate students in clinical psychology. We administered measures
      of stress, psychological health, social support, and coping styles to 53 doctoral
      students in clinical psychology. Current grade point averages were used as a
      measure of academic success. We hypothesized that more successful students would
      likely be healthier and report less stress, more social support, and utilization
      of more positive and less negative coping styles. Results generally supported the
      hypothesis. Unexpected findings were that more successful students were likely to
      be women and to report increased use of focus on and venting of emotion as a
      coping style, increased utilization of medical care, and increased stress
      regarding scholastic coursework.

PMID- 11508018
TI  - Cognitive-affective stress response: effects of individual stress propensity on
      physiological and psychological indicators of strain.
AB  - The purpose of this study was to define further the role of individual stress
      propensity in physiological arousal and subsequent subjective stress and strain
      by measuring stress-induced reactivity in a laboratory setting. Individual
      predisposition to stress is conceptualized as a latent construct, cognitive
      affective stress propensity, that is manifested as multiple trait indicators,
      e.g., negative affectivity, anger-irritability, and negative self-esteem. For 80
      undergraduates experimental treatments were two stressors, time pressure and
      performance feedback. Physiological arousal indices included skin temperature,
      blood volume, and electromyographic activity. Results provide some support for
      the hypotheses that this propensity moderates the relationships between stressor
      and physiological arousal and between physiological arousal and subjective stress
      and strain.

PMID- 11508019
TI  - Formality of researcher's attire and number of terms given by participants for
      six gender labels.
AB  - The number of terms given by participants when experimenters were dressed in
      either professional or casual attire (ns = 20 and 18) was assessed. Participants
      were given 90 sec. to list descriptors for each of six gender-type labels.
      Analyses of variance yielded no significant mean differences for number of items
      listed.

PMID- 11508021
TI  - Type A behavior, social support, and sex in Japanese college students.
AB  - The relations among self-report scores for Type A behavior with social support
      and sex were examined in 239 female and 213 male Japanese college students.
      Scores on Type A behavior were inversely correlated with those for social support
      for both women and men separately. There were no significant differences in the
      magnitudes of these coefficients for women and men.

PMID- 11508020
TI  - Two-year comparison of income, education, and depression among parents
      participating in regular Head Start or supplementary Family Service Center
      Services.
AB  - Changes after 2 years in a Head Start Family Service Center Demonstration Project
      were assessed through pre-implementation and post-implementation interviews with
      80 parents of Head Start children to evaluate changes during the project noted
      for the children's parents. Compared with parents in regular Head Start, parents
      in the supplementary Family Service Center project reported more contact with
      staff, increased their functional literacy scores, and increased their family
      incomes. The percentage of these parents with high depression scores decreased.
      These changes encourage implementation of more intensive social services within
      Head Start programs as a means of effectively assisting Head Start parents.

PMID- 11508022
TI  - Jealousy within the perspective of a self-evaluation maintenance theory.
AB  - We dealt with jealousy in the perspective of a self-evaluation maintenance theory
      which emphasizes the importance of rivals and their characteristics in view of
      the self-concept of individuals. If our study replicates 1996 results of DeSteno
      and Salovey, the finding would support the hypothesis that jealousy is a specific
      process for maintenance of self-evaluation. Thus, a participant should report
      greater jealousy when the domain of a rival's achievements was one of high self
      relevance for the participant. Support for this hypothesis was found under one
      condition. The relevance of a rival's domain to the participant's self-definition
      influenced intensity of experienced jealousy only if the domain was a central
      professional skill (of prospective teachers, namely, "the ability to handle
      children well"). Consequently, the relevance of the other domains used by DeSteno
      and Salovey (1996)--intelligence, popularity, athleticism--is not of unlimited
      validity. In contrast to DeSteno and Salovey, sex differences were significant.

PMID- 11508023
TI  - Relationships among perceived justice, customers' satisfaction, and behavioral
      intentions: the moderating role of gender.
AB  - This article tested the gender differences in the relationships between
      perceptions of justice, customers' satisfaction, and behavioral intentions. The
      sample consisted of 334 subjects (205 men and 129 women) surveyed in 38 hotels
      located in Spain. A questionnaire was used to measure distributive, procedural,
      and interactional justice as well as customers' responses of satisfaction and
      intentions. Analysis showed that the correlation between scores for distributive
      justice and customers' satisfaction as well as that between distributive justice
      and intentions were greater for men than for women. In contrast, the sex
      differences in the links of procedural and interactional justice to satisfaction
      and intentions were not significant.

PMID- 11508024
TI  - The sound of the dentist's drill and students' anxiety scores.
AB  - In a sample of 42 college students, a positive correlation of .51 with sound and
      .56 without sound was found between EMG scores and their total Dental Anxiety
      Scale scores for those who did and did not hear the drill.

PMID- 11508025
TI  - Note on objectives of psychological assessment procedures and the value of
      multidimensional questionnaires and inventories.
AB  - Two different objectives of psychological assessment procedures are identified.
      It is suggested that excessive caution in interpreting and reporting the results
      of such procedures can limit their value.

PMID- 11508026
TI  - Personality predictors of happiness.
AB  - The Oxford Happiness Inventory and a battery of personality measures were
      completed by 171 subjects. The results showed predicted positive correlations for
      happiness with satisfaction with life, self-esteem, and sociability and negative
      correlations of happiness with embarrassability, loneliness, shyness, and social
      anxiety. Four predictors (satisfaction with life, shyness, loneliness, and
      sociability) accounted for 58% of the variance in happiness scores. These results
      support previous research as well as validate the Portuguese version of the
      happiness inventory.

PMID- 11508027
TI  - Psychometric characteristics of the conceptions of mathematics questionnaire.
AB  - This study describes the psychometric characteristics of the 19-item Conceptions
      of Mathematics Questionnaire for a total of 158 students (86 women and 72 men).
      The coefficient alpha of internal consistency reliability was .75. Principal
      components analysis with varimax rotation indicated a two-component solution
      could be extracted. The two theoretically meaningful dimensions were fragmented
      conceptions (alpha = .80) and cohesive conceptions (alpha = .80). The former
      entails seeing mathematics as number rules and formulae to be used to solve
      problems. Students who hold this conception use rote learning and memorization.
      In contrast, the latter entails seeing mathematics as a complex logical system
      for solving complex problems. Students with such a conception approach learning
      to attain, develop, and apply knowledge.

PMID- 11508028
TI  - Determinants of coping: some alternative explanations and measurement issues.
AB  - The determinants of coping may be better understood if we considered the
      different constructs--stressors, strain, and coping within a transactional
      framework: a framework wherein stress is viewed as resulting from the transaction
      between the individual and the environment. Adopting such an approach may also
      require researchers to consider how stressful encounters are appraised--the
      meanings given to events, how coping strategies are classified, and how they are
      used in the coping process, whether linear additive coping scores really tell us
      anything about how individuals actually cope and whether it is now time to
      consider alternative methodologies if we are to better understand the
      complexities of the stress process.

PMID- 11508029
TI  - A field study of the relation between leaders' anticipation of targets'
      resistance and targets' reports of influence tactics used by leaders in dyadic
      relations.
AB  - This research explored the relationship between targets' resistance and leaders'
      behaviors. Barbuto's concentric zones, Preference, Indifference, Legitimate,
      Influence, and Noninfluence, were used as the independent variables to predict
      leaders' use of influence tactics. Results from 83 leader-member dyads imply
      moderate relationships between perceptions of followers' resistance and influence
      tactics used by leaders. Directions for research are addressed.

PMID- 11508030
TI  - Testing the equality of two or more split-half reliability coefficients.
AB  - Methods for testing the equality of two or more split-half reliability
      coefficients as calculated by the Spearman-Brown or the two-part alpha approaches
      are provided.

PMID- 11508031
TI  - Perception of illness among secondary school pupils in South Africa: malaria,
      tuberculosis, HIV/AIDS, and alcoholism.
AB  - The study investigated beliefs of 121 high school students in Grade 11 about
      people who are ill with malaria, tuberculosis, HIV/AIDS, and alcoholism. The
      sample of Black pupils were chosen at random from two rural secondary schools in
      one region in the Northern Province of South Africa. Analysis indicated that
      HIV/AIDS was clearly distinguished from the other three illnesses by being seen
      as the least easily cured, having the most gradual onset, being the most
      contagious, showing the least look of illness, and the patients being likely
      those most blamed for their illness.

PMID- 11508032
TI  - Assessing sexuality attitudes and behaviors and correlates of alcohol and drugs.
AB  - The association between sexual abstinence and use of alcohol, cigarettes, and
      marijuana was examined in data from questionnaires completed by 874 students in
      Grades 6 through 8 at six urban schools. These students participated in a program
      that implemented and evaluated an educational program on abstinence sexuality. It
      focused on raising self-esteem, improving communication skills, and learning to
      set life goals. The evaluation instrument contained items assessing sexuality and
      attitudes toward behaviors related to drug use. Use of each drug (alcohol,
      tobacco, and marijuana) was significantly (p < .00001) and positively associated
      with self-report of having experienced sexual intercourse and expectation of
      having intercourse during the next year.

PMID- 11508033
TI  - Family-of-origin, personality characteristics, and counselor trainees'
      effectiveness.
AB  - This study examined the relationship between counselor trainees' personality
      scores and family characteristics with effectiveness. 56 master's counselor and
      psychologist trainees participated. Analysis suggested that functioning of the
      family-of-origin and MMPI-2 personality traits contribute to the prediction of
      counselor trainees' effectiveness.

PMID- 11508034
TI  - Perceptions of interventions for child sexual abuse in an urban South African
      sample.
AB  - A questionnaire was used to study perceptions of interventions for child sexual
      abuse in a nonrepresentative urban South African population of 132 African/Black
      participants (61 men and 71 women) from the general public of Mankweng. Their
      ages ranged from 21 to 60 years (M age = 32.2 yr., SD = 10.4). Analysis indicated
      these participants clearly supported most of the components of nonadversarial
      approaches. Women were more positive about a nonadversarial approach than men;
      however, participants disagreed on questions about controlling the offender and
      whether an accused relative should move out of the home of the victim.
      Participants supported prosecuting offenders and longer prison sentences and did
      not favour leniency for first-time offenders. They further believed children, the
      family, and even less the offenders should receive treatment.

PMID- 11508036
TI  - Hostility as a feature of elderly suicidal ideators.
AB  - Literature suggests that suicidal feelings are relatively rare in mentally
      healthy older adults. This research investigated the presence of death or
      suicidal ideation in a group of home-dwelling elderly people (N = 611, M age =
      75.7 yr., SD = 7.2), taking into account their psychopathological profiles
      assessed by means of the Brief Symptom Inventory. Suicidality was investigated by
      the Italian translation of the 1974 questions from Paykel, Myers, Lindenthal, and
      Tanner. Elderly with death or suicidal ideation manifested depressive and anxious
      symptoms on the Brief Symptom Inventory. This psychopathological profile, which
      has been reported for these subjects in various contributions to the literature,
      was also characterized by the presence of hostility. The correlation with higher
      scores on the hostility scale is difficult to interpret, although these feelings
      are often accompanied by failure to control impulses, which is an essential
      characteristic in suicidal behaviour.

PMID- 11508035
TI  - A psychometric comparison of the positive and negative affect schedule across age
      and sex.
AB  - This study examined factorial and other psychometric characteristics of the
      Positive and Negative Affect Schedule in relation to mixed-sex youth (n: 234) and
      adult (n: 436) samples. Broadly, the results for both age groups were supportive
      of commonly reported statistical properties of the schedule. Although two factors
      were plainly identified, they were not clearly endorsed for either age group by
      confirmatory indices of fit. Within the adolescent sample, sex differences in
      response to the scales were noted.

PMID- 11508037
TI  - Possible artifacts in memory assessment with the Wechsler Memory Scale-III.
AB  - The Wechsler Memory Scale-III has a number of subtests on which scores can be
      influenced by random answering, malingering, and response sets as well as valid
      variance from memory functioning. Clinicians, researchers, and forensic
      psychologists need to take these possibly confounding sources into account when
      interpreting findings. Chance performance guidelines are presented along with
      some brief examples from clinical assessment.

PMID- 11508038
TI  - Assessing adult ADHD using a self-report symptom checklist.
AB  - The self-ratings of DSM-IV ADHD symptoms by adults reporting a previous ADHD
      diagnosis were contrasted with ratings by controls matched for age and sex.
      Adults previously diagnosed with ADHD endorsed significantly more symptoms of
      inattention and of hyperactivity-impulsivity. Specifically, 13 of the 18 DSM-IV
      ADHD symptoms were endorsed more frequently by the group previously diagnosed
      with ADHD than by the control group. Predictive power analysis showed that
      persons endorsing ADHD symptoms were highly likely to have reported a prior ADHD
      diagnosis. Finally, the data suggested that the DSM-IV diagnostic criteria of 6
      symptoms of inattention or 6 symptoms of hyperactivity-impulsivity could be
      appropriately applied during adult ADHD assessment.

PMID- 11508039
TI  - Spence and Robbins' measures of workaholism components: test-retest stability.
AB  - There has been a recent increase in research devoted to the study of workaholism,
      specifically concerning issues of definition and measurement. The present
      investigation examined the test-retest stability of Spence and Robbins' measures
      of the components of workaholism (1992), one of two measures that has been fairly
      widely used. These measures were found to be relatively stable in a sample of
      early-career managers (n = 67) over a 12-wk. period.

PMID- 11508040
TI  - Immediate feedback during academic testing.
AB  - Performance on two multiple-choice testing procedures was examined during unit
      tests and a final examination. The Immediate Feedback Assessment Technique
      provided immediate response feedback in an answer-until-correct style of
      responding. The testing format which served as a point of comparison was the
      Scantron form. One format was completed by students in introductory psychology
      courses during unit tests whereas all students used the Scantron form on the
      final examination. Students tested with Immediate Feedback forms on the unit
      tests correctly answered more of the final examination questions which were
      repeated from earlier unit tests than did students tested with Scantron forms.
      Also, students tested with Immediate Feedback forms correctly answered more final
      examination questions previously answered incorrectly on the unit tests than did
      students tested previously with Scantron forms.

PMID- 11508041
TI  - Ecstasy is a dangerous drug.
AB  - Ecstasy, a dangerous psychoactive drug, has become a popular recreational drug on
      college campuses and dance halls in the United States, United Kingdom, and around
      the world. No reports on ecstasy have shown addictiveness, and some users of
      ecstasy claim they prefer infrequent use which is not the usual addictive
      pattern. Jaw clenching, bruxism, and some cardiac arrhythmias requiring medical
      attention have been associated with consumption of ecstasy and some fatalities.
      In large scale retrospective questionnaire studies of subjective experiences
      users claimed that they felt a gentle relaxation and openness to others and few
      adversive effects. In rats and monkeys ecstasy has caused depletion of the
      neurotransmitter serotonin in the brain but similar effects have not been
      identified for humans. Case reports have shown panic attacks, flashbacks,
      paranoia, and even fatalities. The Drug Enforcement Administration in 1985 placed
      ecstasy in Schedule I, the most restrictive drug category.

PMID- 11508042
TI  - Training in social skills: an alternative technique for handling disruptive child
      behavior.
AB  - The purposes of this study were to examine the type of response to different
      situations displayed by children with or without conduct disorders and to assess
      the efficacy of the social skills training program herein proposed for modifying
      styles of interpersonal relationship in children. The sample included 315
      children, 8 to 12 years of age. Those exhibiting conduct problems were 164 boys,
      and those having no conduct problems were 151 boys. All participants shared a low
      socioeconomic and cultural status and attended schools located in poor districts
      of Mendoza City in Argentina. Analysis showed that the groups trained in social
      skills improved in social interaction by reducing disruptive behaviors, whereas
      the groups without social skills training showed no behavioral changes. These
      data were confirmed by the teachers' assessments. These results suggest social
      skills training seems an efficient therapeutic approach to the attenuation of
      behavior disorders of boys.

PMID- 11508043
TI  - Progressive muscle relaxation and secretory immunoglobulin A.
AB  - 30 healthy students produced saliva samples for Immunoglobulin A assay before and
      after sessions involving either progressive muscle relaxation (n = 15) or a
      control condition (n = 15). Levels of immunoglobulin A increased significantly in
      the relaxation group but not in the control group.

PMID- 11508044
TI  - The Type A-B behavior pattern in urban and rural men and women.
AB  - This study examined the prevalence of the Type A behavior pattern with Bortner's
      scale in a rural (n = 104) and urban (n = 200) sample of men and women in
      Slavonia, Croatia. The mean score on the Bortner scale for the rural sample was
      significantly lower than the mean for the urban sample. The results support the
      view that rural lifestyle suppresses manifestation of Type A characteristics.

PMID- 11508045
TI  - Body-image attitudes and psychosocial functioning in Euro-American and Asian
      American college women.
AB  - Euro-American (n = 94) and Asian-American (n = 72) college women were compared on
      multiple dimensions of body image, including global body satisfaction,
      preoccupation with appearance, satisfaction with individual body parts or
      features, and weight concern, and psychosocial functioning, including self
      esteem, public self-consciousness, social anxiety, and public body consciousness.
      Both groups reported similar scores on these variables and showed similar
      patterns of correlations between body-image and psychosocial variables. Despite
      similar global body satisfaction, there were group differences in satisfaction
      with individual body parts or features, with Asian-American women reporting lower
      satisfaction with six parts or features and higher satisfaction with one feature.
      Stepwise multiple regression analyses predicting global body satisfaction from
      individual body parts or features suggested that both the specific body parts or
      features most salient to global body satisfaction and the relative influence of
      these parts or features varied as a function of ethnicity. Implications of these
      findings for research and practice are discussed.

PMID- 11508046
TI  - Perception of family support is correlated with glycemic control in Greeks with
      diabetes mellitus.
AB  - We studied 98 native Greek patients with Type 2 diabetes mellitus. Their degree
      of glycemic control, evaluated with glycated hemoglobin A1c levels, was
      correlated with perceived family support, assessed with the Family Support Scale.
      The different social context of Greece--and its corresponding perception of
      family support--influence glycemic control in a way that is at variance from data
      of some studies of Anglo-Saxon families. In conclusion, family support should be
      taken into consideration in the management of native Greek patients with Type 2
      diabetes mellitus.

PMID- 11508047
TI  - Relative roles of cognitive ability and practical intelligence in the prediction
      of success.
AB  - Initial investigations into the construct of practical intelligence have
      identified a new general factor of practical intelligence (gp), which is believed
      to be independent of general cognitive ability. This construct, gp, is also
      believed to be a better predictor of success than cognitive ability, personality,
      or any combination of variables independent of gp. The existence of this
      construct and its independence from Spearman's g is, however, under debate. The
      purpose of the present study is to investigate both the relationship between gp
      and g and the relative roles of practical intelligence and cognitive ability in
      the prediction of success. The participants included 197 college students. Each
      completed both the Multidimensional Aptitude Battery and Sternberg and Wagner's
      measure of practical intelligence in academic psychology. The results of
      structural equation modeling support Sternberg and Wagner's assertion that
      practical intelligence and general cognitive ability are relatively independent
      constructs. Results of regression analysis, however, do not support their
      contention that practical intelligence is related to success after controlling
      for general cognitive ability. Implications of these results for research and
      theory on practical intelligence are discussed.

PMID- 11508048
TI  - Parents' and children's perceptions of interparental conflict resolution.
AB  - This study examined the concordance between parents' assessment of their
      interpersonal conflict resolution with each other and their children's perception
      of the same. 61 parent dyads responded to the 1984 Communication Patterns
      Questionnaire of Christensen and Sullaway while their children completed the 1992
      Children's Perception of Interparental Conflict Scale by Grych, Seid, and
      Fincham. Mothers' and fathers' perceptions of their conflict resolution were
      significantly correlated. Analysis indicated that overall, children's perception
      of interparental conflict was related to their mothers' perception of the
      communication patterns between themselves and their partner. However, this
      relationship was confounded with sex of the child indicated by different patterns
      of intercorrelations between mothers', fathers', and children's perceptions for
      boys and girls.

PMID- 11508049
TI  - [Changes in cause of death determination due to the new Baden-Wurttemberg burial
      regulation].
AB  - In the Burial Ordinance of the State of Baden-Wurttemberg taking effect on 1
      November 2000 some aspects of the post-mortem examination have been revised. One
      of these revisions concerns the determination of the manner of death: In addition
      to the alternatives available so far ("natural death" and "clues to unnatural
      death") there is now the option to classify the death as "unclear"; in this case
      the physician is obliged to inform the local police without delay. The emergency
      doctors working in the ambulance service may restrict themselves to the
      determination of death; if there are grounds suggesting an unnatural death, the
      emergency doctor has to inform the ambulance control station immediately, which
      will then inform the police. Another new regulation is that the post-mortem
      examination has to be performed at the place of death or the place where the body
      was found. Moreover the Ordinance standardizes the obligation to perform a
      "thorough" examination on the undressed body under adequate light conditions. If
      there are clues pointing to an unnatural death or if the body is unidentified no
      changes must be made, in particular the body must not be undressed. The new legal
      situation is described and discussed with regard to its practical implications
      related to the determination of death.

PMID- 11508051
TI  - [An unusual autoerotic accident: sexual pleasure from peritoneal pain].
AB  - The paper describes a fatal autoerotic accident of a 23-year-old man who derived
      sexual pleasure from painful irritation of the peritoneum by sharp force. For
      this purpose he clamped two knife blades into a vice suspended from a rope-pulley
      construction so that he could lower it to pierce the abdominal skin with the tips
      of the knives. When one of the ropes broke, the vice with the knives fell onto
      the man's belly piercing the inferior vena cava and leading to death by
      exsanguination. This, to the authors' knowledge, has been the first ever report
      of a fatal autoerotic accident in which sexual pleasure was to be obtained from
      painful irritation of the peritoneum.

PMID- 11508050
TI  - [Passive exposure in detection of low blood and urine cannabinoid
      concentrations].
AB  - Whenever small amounts of drugs are present in blood or urine samples, especially
      of substances that are preferentially smoked such as cannabinoids, the
      discrimination between active and passive inhalation may cause severe problems.
      The statement of a passive exposure by marijuana smoke has been scrutinized
      reviewing the literature. The pharmacokinetics of smoked marijuana as well as
      experimental data on cannabinoid concentrations in plasma and urine samples
      following passive exposure are summarized. As a conclusion it seems urgent to
      enlarge the existing data base.

PMID- 11508052
TI  - [Detection of the cholinesterase inhibitor tacrine and its main metabolites].
AB  - Tacrine, a cholinesterase inhibitor for symptomatic treatment of minor to
      moderate dementia, and its primary metabolites 1-hydroxy-tacrine and 4-hydroxy
      tacrine were studied by means of thin-layer chromatography, UV spectroscopy and
      gas-chromatography/mass spectroscopy. The analytical data (corrected hRf values,
      UV spectra in solution as well as reflectance spectra, high-pressure liquid
      chromatography data, GC retention indices and EI mass spectra) including various
      derivatization methods are described.

PMID- 11508053
TI  - [Hypostasis-induced changes in the breast area].
AB  - When the anterior thoracic wall is within the hypostatic area, postmortem
      lividity in the region of the nipples and their immediate vicinity is less
      intense or absent. Where hypostatic skin haemorrhages (so-called vibices) are
      present, these are also found outside the areola of the nipple only. This
      phenomenon is visible not only externally, but is particularly pronounced on the
      cut surface. A possible explanation may be the different distribution pattern of
      connective tissue, smooth muscles and blood vessels inside and outside the areola
      mammae. Based on 13 cases from the forensic autopsy material--mostly drug related
      deaths--the macromorphological findings and their histological correlates are
      presented.

PMID- 11508054
TI  - [Determining body height by the femur and femoral fragments].
AB  - Using a forensic series of human specimens, the reliability of frequently-cited
      formulas applied to estimate body height on the basis of the femur was examined
      with regard to their accuracy. Very few proved reliable enough to render accurate
      results. In most cases, less than half of the actual body heights were found to
      have predicted within the single estimation interval. The method to be used for
      such estimations must therefore be selected with great care. Even with partial
      femur measures, it is possible to estimate reliably body height. In particular,
      the circumference of the diaphysis centre correlates well with body height. The
      regression equations calculated in the present study, however, reveal greater
      errors in estimates than the formulas worked out using the total femur length.

PMID- 11508055
TI  - Alveolar ridge preservation during and after surgical tooth removal. Interview.

PMID- 11508056
TI  - Intellectual property rights in agriculture in the light of the debate on
      biotechnology: historical evolution and current situation.

PMID- 11508057
TI  - [The new role of an old enzyme, as studied by A. Clementi, in neurodegenerative
      diseases].

PMID- 11508058
TI  - The use of biotechnology in agriculture and the methods for the detection of
      genetically modified organisms (GMOs) in food.

PMID- 11508059
TI  - Support to the implementation of European Commission policy in the area of GMOs.

PMID- 11508060
TI  - Quantitative analysis of GMO food contaminations using real time PCR.

PMID- 11508062
TI  - PDAs come in handy.

PMID- 11508061
TI  - Biosensors as a new analytical tool for detection of genetically modified
      organisms.

PMID- 11508063
TI  - Laboratory tests Internet culture.

PMID- 11508064
TI  - Wireless catching up, catching on in health care.

PMID- 11508065
TI  - Easy access is key with data repositories.

PMID- 11508066
TI  - New officers prepare to protect privacy.

PMID- 11508067
TI  - Finding qualified I.T. staff members.

PMID- 11508068
TI  - Readers perspectives. Improving patients health and refining the process of care
      delivery.

PMID- 11508069
TI  - Primary drug resistance pattern of mycobacterium tuberculosis in Dhaka,
      Bangladesh.
AB  - One thousand two hundred and eighty one clinically suspected untreated patients
      with pulmonary tuberculosis were studied from an urban tuberculosis clinic in
      Dhaka. Majority of the 1281 patients (77.6%) were from the age group of 14 to 44
      years. Sputum, 106 (8.3%) were found positive for mycobacteria (both by Ziehl
      Neelsen smear staining and culture to consider those as confirmed cases of
      mycobacterial infection. Out of these 106 cases, 101 (95.3%) were identified as
      M. tuberculosis and the rest 5 (4.7%) as Non-tuberculous Mycobacteria (NTM).
      Among the 101 M. tuberculosis strains, 30 (29.7%) were resistant to at least one
      drug; 16 (15.8%); to isoniazid, 11 (10.9%) to rifampicin, 07 (6.9%) to
      streptomycin, 03 (2.9%) to ethambutol and 04 (3.9%) to pyrazinamide. Multi-drug
      resistant tuberculosis (MDR-TB) was found in 5 (4.95%) cases. 5 (4.95%) cases
      were resistant to two drugs and 3 (2.97%) cases to three drugs. Ciprofloxacin was
      tested against 30 strains of M. tuberculosis; 2 (6.67%) of which were resistant.
      This is the first report of ciprofloxacin resistant Mycobacterium tuberculosis
      from Bangladesh. All the 5 strains of NTM tested for said 5 anti-tuberculous
      drugs, were found resistant to more than one.

PMID- 11508070
TI  - Vegetarian diet in the treatment of fibromyalgia.
AB  - Brain tryptophan is low in fibromyalgia. Intake of protein rich in large neutral
      amino acids is reported to lower brain tryptophan. This study was undertaken to
      assess whether any reduction of such proteins by exclusion of animal protein from
      the diet reduced pain and morbidity in fibromyalgia patients. It was an open,
      randomized controlled trial. 37 subjects with fibromyalgia were enrolled in the
      vegetarian diet and 41 in the amitriptyline groups. The outcome was assessed with
      the help of frequencies of fatigue, insomnia & non-restorative sleep, pain score
      on a 10-point VAS and tender point count. Fatigue, insomnia and non-restorative
      sleep were present in 41, 26 and 32 subjects before and in 3, 0 and 0 subjects
      respectively at six weeks of treatment in the amitriptyline group. The pain score
      and tender point count were 6.2 +/- 1.9 & 16.1 +/- 2.3 before and 2.3 +/- 1.3 &
      6.4 +/- 3.0 after treatment. All these differences were significant (P < 0.001).
      In the vegetarian diet group, fatigue, insomnia and non-restorative sleep were
      present in 36, 24 and 27 subjects before and in 34, 29 and 29 subjects at six
      weeks of treatment. The pain score and tender point count were 5.7 +/- 1.8 and
      15.7 +/- 2.4 before and 5.0 +/- 1.8 & 14.7 +/- 3.6 after treatment. All these
      differences were insignificant except that in the pain score. The decrease in the
      pain score, though significant, was much smaller than that in the amitriptyline
      group. So, it may be concluded that vegetarian diet is a poor option in the
      treatment of fibromyalgia.

PMID- 11508071
TI  - Administration of exogenous testosterone in the adult rat and its effects on
      reproductive organs, sex hormones and body-weight.
AB  - The present experiment was performed to observe the effects produced by high dose
      of a testosterone ester on the reproductive organ and body weight changes in the
      adult rat, and to correlate these effects with the serum hormone changes. The
      present study has used the benzoate ester of testosterone (Testosterone benzoate,
      TB) in the adult male rat (300-350 g). The aim was to co-relate the reproductive
      organ and body-weight changes with changes in the serum hormone levels following
      the administration of the ester. TB was injected i.p. for five (5) consecutive
      days at a dose of 100 mg/kg body-weight. The control rats were injected with
      vehicle (arachis oil) at the same dose. The rats were killed on the 6th, 12th,
      18th, 24th and 36th days. Controls for only the 6th and 36th days were kept.
      Reproductive organ weight, body-weight and testosterone (T) levels in serum and
      testis together with serum FSH and serum LH levels were observed. The testes
      weights remained similar (p < 0.05) to those in the control rats until the 18th
      days and were reduced on the 36th day. The epididymis weights were not changed
      until the 36th days, while the androgen-dependent seminal vesicle and ventral
      prostate weights were increased (< 0.05) compared to those in the control rats.
      The body-weights remained unchanged at the 6th day but were significantly (p <
      0.05) decreased on the 36th day. The serum testosterone (ST) concentrations were
      highly raised on the 6th day, came at the control level on the 18th day and were
      significantly decreased (< 0.05) on the 36th day. The testicular testosterone
      (TT) content remained significantly lower (p < 0.05) from the 6th to the 36th
      days post-injection. The serum LH and FSH levels also remained significantly
      lower (p < 0.05) throughout the treatment period. It appears that the elevated
      serum T levels exerted dual effect in the adult rats, namely, enhanced growth of
      the androgen-dependent organs and an inhibition over the hypothalamo-pituitary
      testicular axis. Inhibition of the said axis was evident by the lower levels of
      the serum LH and FSH; probably due to this, the TT-content remained all through
      lower, and perhaps this low TT-content for the long period had led to the low
      testis weights (p < 0.05) on the 36th day. This experiment therefore,
      demonstrates the effects of exogenous androgen administration in the adult male
      rat physiology.

PMID- 11508072
TI  - Incidence of spontaneous echocontrast in left atrium in mitral stenosis detected
      by transoesophageal echo cardiography and related factors.
AB  - The incidence of left atrial (LA) spontaneous echo contrast (SEC) and the
      clinical and echocardiographic variables related to it were prospectively
      evaluated in a series of 60 patients with mitral stenosis (MS) undergoing
      transoesophageal echocardiography (TEE) with a 5 MHz multiplane transducer. LA
      SEC was found in 39 patients (65%) employing TEE. Statistical analysis showed a
      significant relationship between the presence of SEC and MS without mitral
      regurgitation (MR) (P < 0.05), MS with < or = MR grade II (P < 0.05), atrial
      fibrillation (P < 0.001) and increased left atrial dimension (P < 0.05). Age,
      sex, mitral valve area and ejection fraction did not show any positive
      association (P > 0.05). Thus, it is concluded that LA-SEC is a common finding
      observed in approximately 65% of MS patients undergoing TEE and associated with
      conditions favouring stasis of left atrial blood.

PMID- 11508073
TI  - An unusual case of ABO-haemolytic disease of the newborn.
AB  - Haemolytic disease of the newborn (HDN) is a clinical condition in which foetal
      red blood cells are destroyed by maternal alloantibodies directed against red
      cells antigens acquired from the father. These antibodies usually belong to the
      Rhesus (Rh) or ABO blood group systems. ABO-HDN is usually a sub-clinical
      condition and less severe than Rh-HDN. The placenta is relatively impermeable to
      naturally occurring IgM anti-A/anti-B antibodies. However, immune anti-A and anti
      B of the IgG type will cross the placenta and may thus cause ABO-HDN. ABO-HDN is
      the commonest in Group O mothers having A infants. Occasionally it is seen in
      Group O or A (A2) mothers of Group B infants. The most severe disease is seen in
      immune anti-B rather than anti-A antibodies. There are at present no satisfactory
      methods to predict ABO-HDN in the antepartum period. We report here a case of ABO
      HDN where mother who was B, Rh-positive; delivered a baby girl of A1B, Rh
      positive who developed severe haemolytic disease. The baby was the third child.
      To our knowledge this is the first of this kind of severe ABO-HDN in Bangladesh
      and one of the rarest ABO-HDN cases in the world.

PMID- 11508074
TI  - Agranulocytosis--a case report.
AB  - Drug induced agranulocytosis is a rare condition. Yet one hundred and five drugs
      have been claimed to be associated with agranulocytosis and this list has since
      been updated. Some drugs are associated with relatively high risk. Dapsone is one
      of the drugs that was associated with a sufficiently high incidence of fatal
      agranulocytosis. It was withdrawn from use as prophylaxis against malaria. Here
      we present a case of a 27 years old female who had suffered from agranulocytosis
      after taking Dapsone, Amitriptyline and Oflacin for treatment of Dermatitis
      Herpetiformis.

PMID- 11508075
TI  - Designer drugs. What's best for patients isn't always what's best for profits.

PMID- 11508076
TI  - The musical mind. If song has no purpose, why is it deep-wired in the brain?

PMID- 11508077
TI  - Kids' safety is on the line as recalled products stay in use.

PMID- 11508078
TI  - Arsenic at the playground.

PMID- 11508079
TI  - Long-forgotten sunburns later become melanoma.

PMID- 11508080
TI  - Business and health: employer health strategies 2001-2005.

PMID- 11508081
TI  - "Deja-Hillary"--national health reform debate may resurface soon.

PMID- 11508082
TI  - Ten employer solutions to the issues of cost and quality.

PMID- 11508083
TI  - Branemark Novum: prosthodontic and dental laboratory procedures for fabrication
      of a fixed prosthesis on the day of surgery.
AB  - PURPOSE: The purpose of this report is to describe a new technique to fabricate
      and deliver an implant-supported fixed prosthesis to the patient on the day of
      surgery, and to propose a protocol for the prosthodontic and dental laboratory
      procedures. MATERIALS AND METHODS: The development of the Branemark Novum
      prosthodontic protocol is reviewed, and clinical and dental laboratory
      assessments and methods are described. RESULTS: The total treatment time to
      fabricate a permanent implant-supported fixed prosthesis in the mandible can be
      reduced to 1 day with the Branemark Novum technique. The new method includes a
      precise surgical technique using drilling templates for predetermined implant
      positions, a rigid splinting of the implants immediately after placement, the use
      of a prefabricated titanium framework, and elimination of implant impression
      procedures. CONCLUSION: With the technique described in this report, it is
      possible to provide patients with a permanent implant-supported fixed prosthesis
      in the mandible on the day of implant surgery. Patient benefits are obvious, with
      drastically reduced total treatment time, lower cost, and fewer clinical visits.

PMID- 11508084
TI  - Generation of 3-D finite element models of restored human teeth using micro-CT
      techniques.
AB  - PURPOSE: This article describes the development of a three-dimensional finite
      element model of a premolar based on a microscale computed tomographic (CT) data
      acquisition technique. The development of the model is part of a project studying
      the optimal design and geometry of adhesive tooth-colored cusp-replacing
      restorations. MATERIALS AND METHODS: The premolar was digitized with a micro CT
      scanner with a resolution of 13 microns. Surface contours were fitted to the
      various materials, after which a 3-D finite element mesh was constructed to the
      contours. To demonstrate the potential use of the resulting model, it was applied
      to a cusp-replacing resin composite restoration. RESULTS: The stress patterns
      generated in the composite material were truly 3-D. Stress concentrations were
      found at the surface where the load was applied and in the vicinity of the dentin
      composite bonding surface, where the interface had its complex geometry.
      CONCLUSION: The described procedure is an easy method to produce a highly
      detailed 3-D finite element model of a premolar with an adhesive cusp-replacing
      restoration.

PMID- 11508085
TI  - Contrast ratio of veneering and core ceramics as a function of thickness.
AB  - PURPOSE: The recent development of several dental ceramic products has raised
      questions concerning the relative translucency potential of these materials. The
      objective of this study was to test the hypothesis that the contrast ratio of
      dental core and veneering ceramics is a linear function of ceramic thickness.
      MATERIALS AND METHODS: Four groups of disk-shaped core ceramic specimens and four
      groups of veneering ceramic specimens (15 mm in diameter and 0.70, 1.10, 1.25, or
      1.50 mm in thickness) were prepared for analysis. Five disks were randomly
      assigned to each of the eight groups. Four core ceramics were selected for study:
      (1) tetrasilicic fluormica glass ceramic, (2) quadruple-chain silicate glass
      ceramic, (3) barium silicate glass ceramic, and (4) sintered alumina. The four
      veneering ceramics included two feldspathic body porcelains, one fine-grained
      veneering porcelain, and one ultralow-fusing porcelain. RESULTS: There were
      significant differences among the mean contrast ratio values of these materials.
      The most translucent group of the core materials was tetrasilicic fluormica glass
      ceramic, and the least translucent material was sintered alumina. The most
      translucent group among the veneering ceramics was one of the feldspathic
      ceramics (Ceramco), and the least translucent material for all thicknesses was
      the ultralow-fusing veneering ceramic (Duceram LFC). The mean contrast ratio
      values were significantly different at a thickness of 1.50 mm of the four core
      ceramic groups and among the four veneering ceramic groups. CONCLUSION: The
      results of this study indicate that the tetrasilicic fluormica glass ceramic is
      generally the most translucent core ceramic for thicknesses of 0.70, 1.10, and
      1.25 mm, and Ceramco porcelain is the most translucent veneering ceramic.
      However, for a thickness of 1.50 mm, the quadruple-chain silicate glass ceramic
      was the most translucent core ceramic. The relationship between contrast ratio
      and thickness was linear for all ceramics except Vita VMK 68.

PMID- 11508086
TI  - Tooth-implant supported fixed prostheses: a retrospective multicenter study.
AB  - PURPOSE: The purpose of this retrospective multicenter study on implants combined
      with natural teeth was to investigate the implant survival rate and loss of
      marginal bone, as well as indications and complications pertinent to this form of
      implant therapy. MATERIALS AND METHODS: The study comprised 185 implants in 111
      patients from six different clinics in Sweden. Gathering of data, which were
      taken from patient records, followed a strict protocol. The registrations
      included indications for treatment, failure of implants, radiographs from
      baseline and follow-up, and information on complications. RESULTS: The cumulative
      implant survival was found to be 95.4% (standard error 4.5%) up to 3 years of
      follow-up. The marginal bone level at baseline was lower in the maxilla compared
      with the mandible (P = .015), but any further loss did not differ between the
      jaws. The most severe complication other than loss of osseointegration (6/185) or
      periimplant infections (4/183) was intrusion of the abutment teeth, which
      occurred in 5% of the cases. In all instances, the intrusion was seen in
      constructions with nonrigid forms of connection between the implants and teeth.
      CONCLUSION: The tooth-implant supported prosthesis using the Branemark system is
      in the short term an equally predictable treatment as the completely implant
      supported prosthesis concerning implant survival and loss of marginal bone. When
      combining implants and teeth, a rigid form of connection should be used to
      prevent tooth intrusion.

PMID- 11508087
TI  - Implant-supported mandibular telescopic prostheses in oral cancer patients: an up
      to 9-year retrospective study.
AB  - PURPOSE: The aim of this retrospective study was to present the results of
      implant-supported telescopic prostheses in the mandible after removal of
      malignant tumors. MATERIALS AND METHODS: Between 1991 and 2000, 24 patients with
      squamous cell carcinoma (16 irradiated, eight nonirradiated) underwent mandibular
      rehabilitation with implant-supported telescopic prostheses. A total of 111
      dental implants were placed. Treatment complications were observed. The
      cumulative survival rates of the implants and prostheses were evaluated by
      lifetable analysis. RESULTS: Within a mean follow-up period of 30 months (1 to
      108 months), only three implants failed. All other implants are still in
      function. Of 24 patients, 23 were satisfied with their implant-supported
      telescopic restorations. Soft tissue, implant, or prosthetic complications
      occurred very rarely. The cumulative implant survival rate was about 97% and the
      cumulative prosthesis survival rate was about 95% at 9 years. CONCLUSION:
      Implants and implant-supported telescopic maxillofacial prostheses can
      successfully remain in function over a long period. Increased implant and
      prosthetic complications should not be expected. Therefore, telescopic implant
      attachments seem to be very useful as a treatment option for prosthetic
      restoration of the mandible in tumor patients.

PMID- 11508088
TI  - The effect of surface treatment on the shear bond strength of luting cement to a
      glass-infiltrated alumina ceramic.
AB  - PURPOSE: The aim of this study was to evaluate the effect of three different
      surface treatments on the bond strength of four different luting cements--three
      bis-GMA-based resin cements and a compomer cement--to In-Ceram. MATERIALS AND
      METHODS: Eight In-Ceram samples were used for each experimental group. The
      samples were randomly assigned three treatment conditions: (1) etching for 90
      seconds with 5% hydrofluoric acid gel, (2) sandblasting (110-micron Al2O3), and
      (3) tribochemical silica coating. All samples were silanated following the
      surface treatment. The luting cements were bonded to In-Ceram specimens using
      Teflon tubes. All samples were thermocycled for 5,000 cycles altering between 5
      and 55 degrees C with 30-second dwell times. The shear bond strength values were
      measured in a universal testing machine with a cross-head speed of 1 mm/min.
      Analysis of variance was used to analyze data. RESULTS: The mean bond strengths
      varied between 1.2 and 24.7 MPa. CONCLUSION: Shear bond strength of compomer
      cement following tribochemical silica coating was significantly lower in
      comparison to resin cements. Luting of In-Ceram with various resins provided
      varying degrees of bond strengths that were significantly increased by the
      tribochemical silica-coating system.

PMID- 11508089
TI  - The effects of buccolingual width and position of occlusal rest seats on load
      transmission to the abutments for tooth-supported removable partial dentures.
AB  - PURPOSE: The suitable buccolingual width and the location of occlusal rest seats
      for removable partial dentures have not been scientifically established. The aim
      of the present study was to use three-dimensional geometric analysis to evaluate
      the effects of buccolingual width and the location of occlusal rest seats on load
      transmission to the abutments for tooth-supported removable partial dentures.
      MATERIALS AND METHODS: A tooth-supported portion of a maxillary removable partial
      denture with two conventional circumferential cast clasps and an indirect
      retainer was analyzed. Occlusal loading of 100 N was applied to the buccal mesial
      cuspal incline 2.0 mm from the central fossa of the first molar or to the lingual
      mesial cuspal tip. Four combinations of position and width (wide, buccal shift,
      middle, and lingual shift) were simulated. RESULTS: For buccal loading, the wide
      rests and buccal-shift rests produced lower tensile forces at the indirect
      retainer. For lingual loading, the buccal-shift rests produced the lowest
      compressive force to the anterior abutment. CONCLUSION: Based on the tooth
      supported removable partial dentures that were analyzed, buccal shifting of the
      rest seats seems to be advantageous for load transmission to the abutments.

PMID- 11508090
TI  - In vitro repair of three-unit fiber-reinforced composite FPDs.
AB  - PURPOSE: Clinical damage, such as the fracture or abrasion of composite veneers,
      may cause the loss of a fixed partial denture (FPD). Intraoral methods may help
      in repairing and therefore lengthening the life span of the restoration. The aim
      of this in vitro study was to evaluate an intraoral method of repairing fractured
      FPDs made of two different fiber-reinforced composite framework systems.
      MATERIALS AND METHODS: Shear bond strengths of a composite between two different
      fiber-reinforced composite frameworks were determined after five different
      mechanical surface treatments. A silicate-silane coating intraoral air-abrading
      system provided the most reliable bond strength values and was therefore used for
      treatment for the following veneer repair. The repair of 24 three-unit posterior
      FPDs was performed using a restorative composite resin. All FPDs were examined
      after simulating clinical service using thermocycling and mechanical loading.
      Fracture forces were determined for original FPDs and for FPDs after simulated
      intraoral repair. RESULTS: The fracture strength of all original FPDs was about
      900 N. After repair, a maximum decrease in strength of about 15% was determined.
      FPDs that were extremely damaged by cutting the framework showed the lowest
      results, with values of about 450 N. CONCLUSION: The repair of the fractured
      veneer of fiber-reinforced composite FPDs provided good results and therefore may
      lengthen the life span of damaged FPDs. The repair of the fractured frameworks
      showed good results but can only be recommended for limited temporary use.

PMID- 11508091
TI  - Flexural strength of a glass-infiltrated alumina dental ceramic incorporated with
      silicon carbide whiskers.
AB  - PURPOSE: The addition of silicon carbide whiskers has been known to reinforce
      ceramics. This study compared the flexural strength of a glass-infiltrated
      alumina dental ceramic with various amounts of silicon carbide whiskers
      incorporated into the alumina matrix. MATERIALS AND METHODS: Three groups with a
      total of 30 specimens were included: glass-infiltrated alumina dental ceramic
      with 0, 0.125, and 0.25 wt% silicon carbide whiskers. The flexural strength was
      measured using a three-point bending test, and the data were analyzed with one
      way analysis of variance. Scanning electron microscopy was used to examine the
      fracture surfaces of all three materials. RESULTS: There were no significant
      differences in the flexural strength among the three groups. Glass-infiltrated
      alumina dental ceramic failed predominantly by transgranular fracture and to a
      lesser degree by intergranular fracture. CONCLUSION: The addition of silicon
      carbide whiskers did not change the flexural strength of glass-infiltrated
      alumina dental ceramic.

PMID- 11508092
TI  - Factors affecting the fracture resistance of post-core reconstructed teeth: a
      review.
AB  - PURPOSE: This article presents a review of the literature on factors that affect
      the resistance to fracture of post-core reconstructed teeth. MATERIALS AND
      METHODS: Articles cited in a MEDLINE search were obtained from the journals and
      reviewed with respect to factors affecting fracture resistance of post-core
      reconstructed teeth. RESULTS: A large part of the literature reviewed emphasizes
      the stress distribution during insertion of posts and during function. Other
      factors, like post length, post diameter, amount of remaining dentin, post
      material, post adaptability, post design, cement, core material, core and crown
      design, biocompatibility of post material, use of treated tooth, and load
      experienced by restored tooth, are also found to influence the fracture
      resistance of a reconstructed tooth. Of all the factors enumerated, crown design,
      occlusal forces, and use of the treated tooth are found to have direct impact on
      the longevity of the restored tooth. CONCLUSION: Literature indicates that (1)
      preservation of tooth structure is a must; (2) posts should not be used with the
      intention of reinforcing the tooth; (3) review of functional and parafunctional
      forces must be undertaken before restoring the tooth, as these will influence the
      prognosis; and (4) controlled prospective clinical studies evaluating each factor
      should be undertaken.

PMID- 11508093
TI  - Gagging prevention using nitrous oxide or table salt: a comparative pilot study.
AB  - PURPOSE: The objective of this study was to compare two methods for reducing
      gagging induced by stimulation of the soft palate: table salt and nitrous oxide
      inhalation sedation. MATERIALS AND METHODS: Fifteen healthy volunteers, eight men
      and seven women with a mean age of 20.6 years, were subjected to a gagging event
      three times using a large tablespoon to stimulate the soft palate: event 1 =
      spoon alone, event 2 = spoon and table salt on the tip of the tongue with a 30
      minute break between events 1 and 2, and event 3 = spoon and nitrous oxide
      sedation on another day. Time in seconds was measured from the moment the spoon
      touched the soft palate until gagging was felt using a chronometer held by the
      subject. RESULTS: The mean time for eliciting the gagging reaction was 7.7
      seconds for the spoon alone, 8.9 seconds for the spoon and table salt, and 24.0
      seconds for the nitrous oxide sedation. Nitrous oxide inhalation sedation
      significantly (P < .001) reduced the gagging/retching reaction, whereas there was
      no significant time difference in gagging reaction between stimulation with the
      spoon alone or when table salt was added. CONCLUSION: Within the limits of this
      study, table salt did not seem to reduce the time to triggering the gag reflex,
      whereas nitrous oxide had a substantial effect.

PMID- 11508094
TI  - Quantification of masseter muscle deformation during palpation using MRI and
      image-analysis procedure.
AB  - PURPOSE: The aim of this study was to quantify masseter muscle deformation during
      palpation and to discuss the clinical significance of muscle palpation using
      magnetic resonance imaging (MRI) and the image-analysis procedure. MATERIALS AND
      METHODS: Subjects were 10 male volunteers with a mean age of 26.8 years. MRIs
      were taken under two muscle conditions: compressed and noncompressed (control).
      By superimposing a compressed image on a noncompressed image, muscle deformation
      (the cross-sectional area, length of the surrounding area, thickness, circular
      convolution, compressed point, and anterior and posterior extension) was
      measured. RESULTS: The cross-sectional area of the masseter muscle was diminished
      by 14%, circular convolution of the muscle was reduced by 31%, the length of the
      surrounding area was enlarged by 11%, and the thickness of the muscle was reduced
      by 6.7 mm because of compressing. Thus, the masseter muscle was compressed. An
      uneven stretch of the muscle caused by compression was observed at the same time.
      The anterior portion of the masseter muscles extended on average 10%, with great
      individual differences. On the other hand, posterior extension (3%) and its
      individual differences were small. CONCLUSION: The method used made it possible
      to quantify masseter muscle deformation. By compressing, the masseter muscles
      were deformed especially in the anterior direction but with great individual
      differences.

PMID- 11508095
TI  - In vitro comparison of cuspal fracture resistances of posterior teeth restored
      with various adhesive restorations.
AB  - PURPOSE: This study compared the cuspal fracture resistances of posterior teeth
      restored with five different adhesive restorations. MATERIALS AND METHODS: Eighty
      four sound human molars were included in this study. Sample molars were divided
      into seven groups. The first five groups received mesio-occlusodistal cavity
      preparations and were restored with (1) amalgam combined with urethane
      dimethacrylate cement, (2) posterior composite, (3) direct composite inlay, (4)
      cast-metal inlay, and (5) complete ceramic inlay. The sixth and seventh groups
      were introduced in the study as controls. Samples of group 6 were prepared but
      were tested without restoration (prepared-only group). Samples of group 7 were
      intact teeth and were tested as unprepared. All samples were loaded axially until
      failure. RESULTS: While the unprepared teeth had a significantly higher
      resistance than all other groups, the prepared-only teeth were the weakest. No
      significant differences were found in resistance to cuspal fracture among the
      restoration groups. CONCLUSION: The difference between the mean cuspal fracture
      resistance of the unprepared and prepared-only groups was statistically
      significant. Restoration groups were stronger than the prepared-only group.
      However, differences between the restoration groups were insignificant.

PMID- 11508096
TI  - Five-year evaluation of posterior all-ceramic three-unit (In-Ceram) FPDs.
AB  - PURPOSE: The purpose of this study was to investigate whether the properties of
      the In-Ceram material are adequate for use in posterior three-unit fixed partial
      dentures (FPD) and to evaluate the clinical method regarding preparation
      technique, design, and choice of cement. MATERIALS AND METHODS: Eighteen patients
      were treated with a total of 20 posterior three-unit FPDs according to the In
      Ceram technique. The FPDs were constructed with bilateral support and one pontic
      and were all replacing one premolar or a molar (11 replacing premolars and 9
      replacing molars). They were evaluated 6 months after delivery and then once
      yearly. RESULTS: Eighteen of the 20 FPDs (90%) showed no defects at any of the
      follow-up examinations and were functioning well after 5 years. No caries or
      signs of gingivitis or periodontitis exceeding those found in the rest of the
      dentition were registered. CONCLUSION: The In-Ceram technique is, in a 5-year
      perspective and adopted for three-unit FPDs, an acceptable treatment alternative.
      Further studies must, however, be performed before the material can be
      recommended for more extensive restorations than the FPDs included in this study.

PMID- 11508097
TI  - Whealth study: women's reports of childhood abuse.
AB  - Most samples of adult women will contain a significant proportion who have been
      or are currently in abusive relationships. While past research has linked
      childhood abuse of girls to adult health concerns, little is known about the
      process through which women retrospectively reconcile these experiences. This
      article reports on data collected in an ongoing project on midlife women's
      health. Twenty-seven of 50 urban, middle-class participants in this phase of the
      project reported childhood abuse experiences. In the analysis, several aspects of
      these experiences were identified: definitions of abuse; recontextualizing abuse;
      responsibility for abuse; abuse avoidance; and experiences of multiple abuse. The
      women's discourse reflected a number of ideologies that provide a context in
      which women negotiate their understandings of these childhood experiences. This
      article provides insight into our understanding of abuse. It addresses the
      fundamental issue of promoting a worldview that precludes child abuse while
      leaving adult survivors with options for "moving on."

PMID- 11508098
TI  - Surreptitious learning: menarche and menstrual product advertisements.
AB  - The purpose of this study was to examine the messages conveyed in menstrual
      product advertisements with specific concern given to information that could be
      learned about menstruation and the female body by menarcheal girls. Over 200
      advertisements from popular women's magazines were analyzed using constant
      comparative analysis. The core variable was Heightening Insecurities. The themes
      identified in menstrual product advertisements function to heighten insecurities
      in the female adolescent reader. The findings revealed that the advertisements
      were a reflection of the negative societal views of menstruation and, because the
      advertisements function to heighten insecurities, they also function to
      perpetuate and maintain the silence and shame which surrounds menstruation in our
      society.

PMID- 11508099
TI  - Participatory action research: lessons learned with Aboriginal grandmothers.
AB  - Participatory action research is evolving as both a research methodology and an
      intervention for health promotion. Here we describe its use in conducting a
      health assessment as part of a larger project for older Aboriginal women
      (hereafter known as the grandmothers). The overall purpose of the project was to
      study the women's health needs and respond through health promotion programming.
      The experience of using participatory action research revealed a number of
      lessons, including challenges and points of tension, and determinants and
      indicators of success. The research team identified some implications for
      consideration by others interested in participatory action research.

PMID- 11508100
TI  - Medicalization and women's knowledge: the construction of understandings of
      infant feeding experiences in post-WW II New Zealand.
AB  - For most of the twentieth century infant feeding knowledge has been constructed
      by medical scientists and health professionals. However, for a short time around
      the 1970s, New Zealand women (re)claimed the power to author their own knowledge
      based upon experience. This coincided with a dramatic return to breastfeeding on
      a national scale. Using New Zealand women's narratives of their infant feeding
      experiences over the past 50 years, this article brings to the foreground the
      importance of women's subjective construction of knowledge, their positioning
      within it, and the suppression of rudimentary discourses when that power is
      removed or relinquished in the process of remedicalization.

PMID- 11508101
TI  - The breastfeeding support team for low-income, predominantly-minority women: a
      pilot intervention study.
AB  - This quasiexperimental pilot study explored whether a focused breastfeeding
      intervention had potential to improve outcomes in low-income breastfeeding women.
      Twenty breastfeeding women (10 in intervention and 10 in usual care) were matched
      on type of delivery, previous breastfeeding experience, and race. Women were low
      income, young, 65% high school graduates, and 40% minority. For this
      intervention, the BST, a breastfeeding support team (community health nurse and
      peer counselor) provided hospital and home visits and telephone support. Outcomes
      were measured weekly for the first month, and monthly through month five. At all
      time periods, more women who received the intervention were breastfeeding.
      Further, they had less nipple discomfort in the first month; significantly less
      fatigue in month four and at three and five months reported less fatigue,
      depression, and anxiety.

PMID- 11508102
TI  - Retrospective clinical investigation of the impact of early treatment of children
      with Down's syndrome according to Castillo-Morales.
AB  - BACKGROUND: Infants and toddlers with Down's syndrome are treated at the
      Department of Orthodontics, University of Frankfurt/Main only when the tongue
      protrudes over the lower lip, hindering mouth closure. No plate therapy is
      applied in patients with less tongue protrusion. This study aimed to assess
      objectively the treatment effects of stimulation plate therapy after Castillo
      Morales at this early stage of development. PATIENTS AND METHOD: The follow-up
      covered 33 children, 20 of whom showed no mouth closure with the tongue resting
      protrusively on the lower lip at first examination at the age of 8 months. These
      20 children received orthodontic treatment based on a stimulation plate. The
      parents were advised to insert the plate four times a day for about half an hour
      respectively. The overall treatment time was ca. 2 years. The second group (13
      children) received no early treatment, as the functional parameters were only
      slightly altered at the age of 7 months. At follow-up, the children of the
      treatment group were between 8.8 +/- 2.3, and those of the control group 8.9 +/-
      3.0 years old. The children underwent clinical examination; the parents answered
      a questionnaire. Additionally, study casts and intraoral photographs were taken
      along with frontal and profile photographs. The factors assessed were various
      functions, dentition, facial development, and subjective rating of the parents.
      RESULTS: In contrast to the initial findings, no difference between the two
      groups was found at follow-up. CONCLUSION: Early treatment using a stimulation
      plate thus appears to mitigate or even normalize the initially more severe
      dysfunctions recorded in the study group as compared to the controls.

PMID- 11508103
TI  - Functional processes when wearing the SII appliance during the day.
AB  - In 20 subjects the neuromuscular activity during the day was divided into six
      different activities and recorded. In the case of typical application of the SII
      appliance for 4 hours in the afternoon and the free organization of this time by
      the patient himself, most of the time fell into the area "intellectual activity"
      followed by the area "manual activity". Since the term "functional orthodontics"
      naturally describes the function, this should be realized most impressively when
      wearing such an appliance during the day. During the day there are mouth opening
      and closing movements of varying frequency with quite different amplitudes.
      Conversation as well as reading a text aloud can be considered favorable in terms
      of neuromuscular adaptation. Obviously, the relatively short habituation period
      soon results in the patient not needing the bars as guiding bars any more (this
      is in contrast to investigations during nocturnal sleep). In other words, the
      patient needs them only for a brief time to influence the muscles in such a way
      that the neuromuscular masticatory pattern is virtually independent of the bars.
      Only during intellectual and practical activity does the patient rest on the
      inclined plane with the help of the bars and execute small movements.
      Consequently, wearing the SII appliance during the day can be regarded as
      extremely important to the success of treatment. Important neuromuscular
      influences occur while doing homework as well as during intellectual activity.
      Wearing the appliance during the day corresponds to neuromuscular programming, so
      that the term "functional orthodontic appliance" is completely correct. Since
      there are only about 600 biting actions during the night, a functional
      orthodontic appliance should definitely be worn for a certain time during the day
      too, in order not to jeopardize the neuromuscular adaptation.

PMID- 11508104
TI  - Skeletal and dental effects of maxillary protraction in patients with angle class
      III malocclusion. A meta-analysis.
AB  - The aim of this study was a quantitative review of the published results
      concerning the treatment effects of maxillary protraction in patients with Angle
      Class III using the meta-analysis method. 85 articles published between 1966 and
      1998 were reviewed under strict, pre-defined criteria. Of these, 12 studies
      presenting results of cephalometric measurements were selected for further
      analysis. The results of different cephalometric measurements were reviewed with
      Dstat 1.10 software in order to calculate a standardized treatment effect
      variable. The homogeneity of the variances of the different effect variables as
      well as a composite effect were calculated. For the latter, each individual
      effect variable was weighted by the reciprocal of its variance, with predefined
      study characteristics being used for categorical model calculations. Our results
      showed a significant composite effect of the therapy on the skeletal components
      (SNA: 1.4 degrees, composite effect = 1.11; SNB: -1.3 degrees, composite effect =
      -0.94; ANB: 2.6 degrees, composite effect = 1.73; lower anterior face height: 1.6
      mm, composite effect = 0.85) as well as on the dental components of the face
      (inclination of upper incisors: 1.6 degrees, composite effect = 0.37; inclination
      of lower incisors: -3.7 degrees, composite effect = -0.87). However, several of
      the individual effect variables demonstrated a significant lack of homogeneity.
      Study characteristics which might possibly account for this variability were the
      patients' ages at the start of treatment and the combination of maxillary
      protraction with rapid maxillary expansion. In summary, maxillary protraction was
      shown to have a significant treatment effect. The meta-analysis method proved to
      be a valuable tool in judging the current status of a given clinical therapeutic
      concept.

PMID- 11508105
TI  - Root resorptions in upper first premolars after application of continuous torque
      moment. Intra-individual study.
AB  - MATERIAL AND METHOD: With the purpose of investigating the occurrence,
      localization and extension of possible root resorptions after fixed appliance
      treatment with a continuous torque force, 28 upper first premolars
      orthodontically indicated for extraction from 14 patients were analyzed by
      scanning electron microscopy. Tooth movement was carried out with continuous
      moments of different magnitudes (300 cNmm, and 600 cNmm), using a biomechanical
      model with superelastic wires (stainless steel-NiTi-SE), which was specially
      designed and individually calibrated. The teeth were divided into one control
      group with four premolars (non-moved) from two patients, and two experimental
      groups (300 cNmm and 600 cNmm respectively) with six patients each. Each group
      was distributed intra-individually as follows: the right first premolar of six
      patients was extracted after 1 week of movement, the left first premolars were
      removed after 2, 3 and 4 weeks. After extraction, teeth were fixed, treated with
      2% sodium hypochlorite solution for 6 hours in order to remove the organic tissue
      components, dehydrated, and metal-coated in a Balzers SCD 050 apparatus. RESULTS:
      The analysis in a scanning electron microscope (Jeol 6100, at 10-15 kV) revealed
      many resorption lacunae in the root surface, mainly on the lingual side in the
      apical third of the roots. Resorption processes were also observed on the buccal
      root surface in the cervical third. All experimental teeth showed resorption
      areas. Teeth which had been moved for a longer time period and with a higher
      magnitude of applied moments showed a higher degree of root resorption in width
      as well as in depth. Higher magnitude of moments produced exposure of root
      dentine, evidencing pronounced root resorption.

PMID- 11508106
TI  - A new carbide finishing bur for bracket debonding.
AB  - BACKGROUND: The removal of residual bonding resin with rotary instruments after
      bracket debonding may damage the enamel surface. Conventional carbide burs may
      scratch the enamel due to the shape and sharpness of their blades. CARBIDE
      FINISHING BUR: A new carbide finishing bur with a slightly tapered shape, rounded
      tip and eight twisted blades has been developed. As a special feature the wedge
      angle of the blades has been enlarged to ca. 130-135 degrees by means of an
      oblique ground chamfer (relief angle ca. 0-5 degrees). The transition from head
      to shaft has been smoothed off with a safety chamfer. Overall, the cutting
      capacity has been reduced in the enamel, while the bur has remained sufficiently
      sharp within the adhesive resin. PROTOTYPE TESTING: For prototype testing,
      incisor brackets were bonded in vitro to 70 human incisors according to the
      standard clinical technique and removed after 7 days. Residual bonding resin was
      removed with conventional carbide burs and with gradually modified prototypes of
      the new finishing instrument respectively. The resulting enamel surfaces were
      evaluated by scanning electron microscopy. The specimens were then treated with a
      polishing paste and evaluated again. RESULTS: Conventional carbide burs remove
      not only residual bonding resin but also some enamel; scoring may occur. The
      newly developed finishing bur has been proven by morphological evaluation to be
      less aggressive in removing residual bonding resin after bracket debonding.

PMID- 11508107
TI  - The complex case--unforeseeable findings and interdisciplinary treatment.
AB  - Orthodontic treatment is described in a case requiring an early treatment start
      due to disturbed eruption in the upper front, with displacement of an upper
      central incisor, tongue dysfunction and Class III tendency. The further course
      revealed additional problems which had been unforeseeable at treatment onset:
      ankylosis of the lower left first molar and dehiscences in the lower front.
      Treatment duration was very long due to treatment measures overlapping. The
      interdisciplinary treatment measures are outlined and the difficulties posed by
      contractual guidelines are pointed out.

PMID- 11508108
TI  - [Three fourths of medical endeavors. An interview with Professor G. A. Nagel by
      K. Reinhardt].

PMID- 11508109
TI  - [Palliative treatment of brain metastases with gamma knife].
AB  - The gamma knife is a stereotactic radiosurgery device which allows well defined,
      deep seated brain tumors or arteriovenous malformations with a maximal volume of
      about 25 ccm and a diameter not greater than 3.5 cm, to be treated in a single
      session under local anesthesia. The gamma knife offers an alternative treatment
      method to the classical approach of treating brain metastases by surgical
      excision and/or whole brain radiotherapy. The advantages of this technique are
      evident: the method is non-invasive, the treatment is carried out in a single
      session with a very short hospitalisation of two to three days, it is exempt from
      physical and psychical stress, the head does not need to be shaved and no hair
      loss occurs, a good quality of life is obtained for a reasonably prolonged
      survival time and it offers an economically favourable treatment method. Up to
      December 1999, over 30,000 patients suffering from brain metastases have been
      treated worldwide using the gamma knife. In Zurich, from September 1994 to
      December 2000 140 received this treatment. In the literature selection criteria
      may differ, and this may have determined some of differences in outcome. However,
      our results are comparable with those in the majority of publications with an
      average survival time of 263 days and a maximum survival of 1080 days. Good
      prognostic factors for survival and local control of brain metastases are a
      Karnofsky Performance Scale Score approaching 90 to 100, but not lower than 70,
      tumour volume, controlled primary cancer, and absence or stable extracranial
      metastases.

PMID- 11508110
TI  - [Palliative immunotherapy of cancer].
AB  - In addition to surgery, chemotherapy and radiation, immunotherapy of cancer
      resembles a potential treatment strategy for patients with cancer. To strengthen
      the immune system might help to control or even to eradicate malignant tumors.
      Immunoaugmentative strategies include biological response modifiers as
      interferons and interleukins. Recently, monoclonal antibodies directed against
      tumor associated antigens and coupled with radioisotopes or cytotoxic agents have
      become available. Adoptive immunotherapy uses immune effector cells, i.e. T-cells
      or natural-killer cells that are activated in-vitro by appropriate cytokines.
      Dendritic cells, either unstimulated or pulsed with tumor derived molecules have
      shown promising anticancer activity in selected tumors. Immunonutrition, that is
      the manipulation of immune phenomenons through edibles is a new and interesting
      topic. Immunologic strategies for the treatment of malignant diseases are
      currently under intensive preclinical and clinical investigation. Further
      insights into the mechanisms of host-defense against cancer cells and the
      modification of immune-effector cells might pave the way to efficient treatment
      strategies, even in the palliative setting.

PMID- 11508111
TI  - [Eleven years of experience with permanently implanted port-systems in 329 cancer
      patients].
AB  - Intravenous port-systems are predominantly used for long-term chemotherapy in
      oncology. 164 of our patients were implanted with a Port-a-Cath and 165 patients
      with a Chemosite system. Indications, the duration of implantation, the duration
      of use, the access and complications were analysed. This retrospective study
      analyses 329 tumor patients, who have been treated at the Cancer Center Klinik im
      Park from September 1987 until February 1998. The preferred access of
      implantation were: v. subclavia (47%) and v. cephalica (35%). The average
      duration of implantation was 279 days for the Port-a-Cath system and 443 days for
      the Chemosite system. The most frequent complication immediately following
      surgery was a pneumothorax in 4% of the patients. The frequency of late
      complications was: thromboses 2%, infections 4%. This study analyses our
      experiences with fully implantable permanent intravenous catheter-systems in 329
      tumor patients. These catheters can be used for very long periods with a low rate
      of complications.

PMID- 11508112
TI  - [Palliative surgery for primary and secondary thoracic malignancies].
AB  - Palliative thoracic surgical interventions aim to assure or to improve quality of
      life. They encompass surgical correction of vital complications, treatment of
      symptoms that limit daily activities, and prophylactic interventions to reduce
      symptoms and improve prognosis. Interventions are based on statistically proved
      results as well as on profound clinical experience in oncologic surgery. Because
      palliation does not intent to cure, such operations require precise patient
      information and inclusion of the respective patient in decision making.
      Operability depends on patient general condition and extent of the procedure. If
      tumor is resected local radicality is the principle goal also in palliative
      situations, which is adapted to each individual case, especially in the context
      of multimodal treatment strategies. One of the main indications of palliative
      thoracic surgery in pulmonary metastasectomy. Using the new laser technology loss
      of parenchyma is minimal and the rate of lobectomies is reduced from 25% to 4%.
      With mortality and morbidity of less than 1% the 5-year survival after complete
      metastasectomy is more than 30%. Tumors of the thoracic wall cause pain and tend
      to exulcerate; due to their obvious presence they induce anxiety. Their removal
      and subsequent plastic surgery of the chest wall defect therefore makes sense
      also in advanced stages. Palliative and curative surgery is one of the pillars in
      plurimodal treatment of mediastinal tumors, besides its role in obtaining tissue
      for histologic diagnosis. Thoracoscopic talc pleurodesis has a success rate of
      more than 90% in malignant effusions if the lung is fully expandable.

PMID- 11508113
TI  - [Role of palliation in the care of the elderly].
AB  - Palliative care in the elderly appropriately takes place within a spectrum of
      curative, rehabilitative, preventive, and chronic disease management
      interventions, and seeks to optimize quality of life. Setting priorities among
      numerous legitimate treatment goals is the central task in the care of
      chronically ill frail individuals. Decision-making can be challenging when the
      goal of providing comfort comes into conflict with the goal of prolonging life,
      and should be guided whenever possible by consistently expressed preferences of
      the patient. The assessment and relief of distressing physical and psychological
      symptoms should receive active attention at all stages in the care of the frail
      elderly, both in the context of acute medical and surgical interventions and
      during the terminal phase of life. Pain and dyspnea are frequently reported by
      significant proportions of elderly individuals hospitalized for chronic lung
      disease, heart failure, and cirrhosis as well as for malignancies. In the
      treatment of dementia, the types of interventions that improve quality of life
      will differ in the early and late phases of the illness.

PMID- 11508114
TI  - [Palliative psychosomatic medicine].
AB  - Psychotherapeutic medicine, the area of medicinal specialisation dealing with the
      foundations of psychosomatic medicine, so far dealt mostly with diagnosis and
      therapy of acute diseases. The course of illness in patients with bio-psycho
      social disorders however ist most often chronic. Sigmund Freud the founder of
      scientific psychotherapy himself was a patient in palliative care for 26 years
      and underwent over 30 surgical procedures to treat his carcinoma of the palate
      and jaw. Some goals and psychotherapeutic strategies of intervention that can be
      used in palliative psychosomatic medicine are laid out. This important field has
      in itself so far not reached a wide spread recognition and there are hardly any
      theoretical concepts or empirical validation to be found.

PMID- 11508115
TI  - [What is the benefit of oncological rehabilitation programs for cancer patients
      in palliative care?].
AB  - Medical and psychosocial rehabilitation of cancer patients is deeply integrated
      into the German health system. In contrast to the majority of other European
      countries and the United States of America, rehabilitation is mainly done as
      inpatient care and only rarely in outpatient units. In curative treated cancer
      patients the main goals of rehabilitation include recovery from physical
      impairments, adaptation to functional disabilities and improvement of
      psychosocial functioning, including the ability to go back to work. In palliative
      cancer patients the improvement of health adjusted quality of life, the avoidance
      of permanent supportive care and the social integration are the major goals.
      Cancer rehabilitation needs an interdisciplinary strategy between medical,
      psychooncologic, physiotherapeutical and educational professionals. To attain a
      benefit for the individual cancer patient as well as for the medical system it is
      important to clearly define the rehabilitation needs and design a most individual
      rehabilitation program adjusted to the personal needs of the patient. A
      systematic quality management since 1995 of German rehabilitation clinics and
      rehabilitation programs did significantly improve this part of the professional
      health system. However it is necessary to add more outpatient units for cancer
      rehabilitation to reach more flexibility and satisfy the demand of patients for
      more home located support.

PMID- 11508116
TI  - [Rehabilitation of the anterior portions of the maxilla and mandible by means of
      implants and bone grafts].
AB  - This article describes the possibilities and difficulties of reconstruction in
      the front regio by means of implants and bone transplants in five patients. First
      of all, planning is the most important step. Sometimes the class III relationship
      is a real challenge. Different bone transplants, the inlay and onlay technique,
      the number of the implants, the importance of the way the implants are uncovered
      in the second stage are discussed. In the front region, we aim for functional and
      esthetic reconstruction.

PMID- 11508117
TI  - [Treatment of a congenitally missing upper lateral incisor with an implant].
AB  - The presentation of a case where an agenetic lateral tooth was replaced by an
      oral implant, has been described. The following parameters are important: oral
      hygiene, the moment of implant surgery, presurgical orthodontic treatment,
      alternative prosthetic treatment possibilities and recall of the patient.

PMID- 11508118
TI  - [Incidence and primary prevention of complications related to the placement of
      dental implants].
AB  - Despite high success rate with endosseous titanium implants, failures inevitably
      occur. At an early stage, lack of primary stability, surgical trauma,
      peroperative contamination and occlusal overload seem to be the most important
      causes of implant failure. Many authors have reported that implant failures after
      primary healing and osseointegration are mainly due to peri-implant infection
      and/or excessive occlusal stress. Like periodontal disease, peri-implant
      inflammatory lesions develop as a result of plaque accumulation and exhibit
      similar clinical and microbiological signs as encountered for periodontitis.
      Clinicians should therefore enforce preventive measures to decrease the
      prevalence of such causative agents. Therapeutic attempts should have their
      rationale in the restoration of a biomechanical and/or host-bacterial
      equilibrium. The major limitation at this point seems to be the detection of a
      pathological process. Aside from clinical evaluation, the interpretation of
      radiographic images is one of the most frequently applied diagnostic procedures
      in patients with osseointegrated implants. Post-therapeutic maintenance care is
      an integral part of the entire implant treatment approach.

PMID- 11508119
TI  - [Simplification and rationalization of oral implantology].
AB  - A number of rules, often considered as dogmas by some, made it possible for oral
      implants to achieve a high success rate. However, some of these concepts have
      been questioned. Indeed, the submerged fashion of implant placement, the
      arbitrary 3 to 6 months healing period, bicortical anchorage, placement of the
      longest possible implants, as well as implant placement in strict sterile
      conditions have been scientifically challenged. The aim of this article is thus
      to give a critical review of these concepts, in order to further simplify and
      rationalize oral implantology, putting this field in the reach of a bigger number
      of patients and practitioners. However, procedural simplification in oral
      implantology is not synonymous to poor patient preparation. On the contrary, an
      in-depth knowledge and experience in both the surgical and prosthetic aspects of
      oral implantology are of utmost importance in order to achieve a high success
      rate.

PMID- 11508120
TI  - [Vertical augmentation of the alveolar process by distraction osteogenesis].
AB  - This article describes the treatment of a boy with Class II deep bite and
      hypoplasia of the alveolar process due to agenesis of the canines and premolars.
      At first, the occlusion has been adjusted by advancement of the mandible and
      opening of the bite after bilateral sagittal split osteotomy. Later, under local
      anaesthesia, a segmental osteotomy of the hypoplastic alveolar process has been
      performed. Distraction of the hypoplastic alveolar process has been achieved by
      orthodontic traction on the residual dentition in the segments. After sufficient
      augmentation of the alveolar process, 6 implants for two bridges have been
      placed.

PMID- 11508121
TI  - [Less invasive sinus lift using the technique of Summers modified by Lazzara].
AB  - The sinus floor elevation (sinus lift) is a procedure used for treating patients
      with very large pneumatisation of the maxillary sinus and thereby with severe
      atrophic maxilla (height of the residual alveolar bone between 5 and 8 mm). A
      modification of this technique is the osteotome sinus floor elevation: this is a
      less invasive method of creating sites with osteotomes by crestal approach in
      locations with insufficient bone for insertion of oral implants. With larger
      osteotomes, bone graft substitutes are placed through the osteotomy site to
      provide a sinus floor elevation and an augmentation of the crestal bone.
      Therefore, via the osteotome technique, longer oral implants can be inserted.

PMID- 11508122
TI  - [Use of PRP (Platelet Rich Plasma) in bone volume augmentation].
AB  - Blood platelets are the main source of different bone healing and growth factors.
      Their role and use in sinuslifting will be discussed. Finally we discuss the
      technique and the results in our patient population.

PMID- 11508123
TI  - [Chin grafts].
AB  - This article describes various procedural steps undertaken during the chin graft
      technique used in our department. The recommendations and possible complications
      are described in detail and discussed using the scientific literature. A short
      theoretical introduction on bone healing is presented in order to better explain
      the proposed techniques.

PMID- 11508124
TI  - [Responsibility and legal aspects of implantology].
AB  - Medico-legal aspects regarding oral implantology are to be found in the Civil
      Right and governed by the Belgian civil code (article 1382) and by the specific
      nature of the relationship between the practitioner and the patient. Both the
      patient and the practitioner are to fulfill a number of obligations. One of
      these, is the compulsory 'informed consent' to be obtained from the patient.
      However, this consent is preceded by the information given and repeated by the
      practitioner to the patient regarding the proposed treatment. This article
      describes precautions and obligations to observe by the practitioner in order to
      minimize the possibility of being sued by a patient. Various anamnestic question
      lists are provided in this article.

PMID- 11508125
TI  - [Innovation in Hellenistic surgery: cataract operation].

PMID- 11508126
TI  - [Healing in the ancient Orient].

PMID- 11508128
TI  - Spa Bad Elster, Bad Elster, Germany.

PMID- 11508127
TI  - [Medical ethics as health policy. On the French discussion of human
      experimentation after 1945].

PMID- 11508129
TI  - USG presents specifying for performance: understanding key specification criteria
      for walls, ceilings and floors.

PMID- 11508130
TI  - Energy-saving lighting: no more excuses.

PMID- 11508131
TI  - Frequency of radiographic caries examinations and development of dental caries.
AB  - The general aim of this thesis was to evaluate whether a change in the threshold
      for surgical intervention in the caries process can be consistent with a stricter
      attitude towards the use of radiographic caries diagnosis. Bitewing radiographs
      of 3 groups of patients were retrospectively studied. Two groups comprised 229
      patients, 18 years old at the end of the study in 1984. 102 had lived in an area
      with 1.2 ppm water-fluoride content (F84-group) and 127 in an area with 0.02 ppm
      fluoride content (O84-group). In the 3rd group 285 patients, 19 years old at the
      end of the study in 1993, lived in an area with 1.2 ppm water-fluoride content
      (F93-group). The latter patients were managed according to a restrictive attitude
      to surgical intervention and radiographic diagnosis of caries. The prevalence of
      patients and the frequency of tooth surfaces with caries was significantly lower
      in the fluoride groups than in the non-fluoride group. The correlation between
      patients' accumulated number of posterior proximal lesions and fillings at the
      last examination and the mean interval between their bitewing examinations was
      weak in all groups. The mean interval between examinations was significantly
      longer in the F93-group than in the other 2 groups. By applying an algorithm for
      individualisation of examination intervals these could be prolonged depending on
      the accepted risk for the development of inner dentin lesions. Future development
      of proximal dentin lesions was rather well predicted by means of past caries
      experience as demonstrated by ROC-analysis. The proportion of inner dentin
      lesions that were operatively treated was significantly higher in patients from
      the F93-group than in those from the other 2 groups in which a less strict
      attitude towards operative treatment was used. In the F93-group the average
      survival time of enamel and outer dentin lesions was 8.0 and 3.4 years,
      respectively, when right censored data were taken into account. In populations
      with low caries prevalence a strict threshold for operative treatment of proximal
      lesions can be consistent with prolonged intervals between radiographic
      examinations without an increased risk of pulp involvement. A skewed distribution
      of the patients with regard to caries experience was found in all 3 groups. Thus,
      even in low prevalence populations the intervals between radiographic
      examinations must be individually determined and coupled with individualised
      preventive care.

PMID- 11508132
TI  - Riboflavin treatment of antiretroviral induced lactic acidosis and hepatic
      steatosis.
AB  - BACKGROUND: Antiretroviral induced lactic acidosis and hepatic steatosis is a
      rare syndrome caused by inhibition of deoxyribonucleic acid (DNA) polymerase
      gamma by the Nucleoside Reverse Transcriptase Inhibitor (NRTI) class of
      antiretrovirals. There have been recent reports of NRTI-induced lactic acidosis
      treated with high-dose riboflavin. INTERVENTION AND RESULTS: We report a case of
      NRTI lactic acidosis reversed with high-dose riboflavin. Treatment with 50 mg of
      riboflavin per day was initiated on hospital day 10 after the patient developed
      respiratory failure. Arterial lactate decreased from 11.9 mmol/dL to 2.1 mmol/dL.
      Despite lactic acidosis reversal the patient developed acute respiratory distress
      syndrome (ARDS) and expired. Autopsy confirmed extensive hepatic steatosis with
      no infectious agents identified. CONCLUSION: Nucleoside Reverse Transcriptase
      Inhibitor lactic acidosis will likely become more prevalent with the trend toward
      aggressive antiretroviral treatment. This report provides additional support for
      the efficacy of riboflavin treatment to reverse this serious complication of
      antiretroviral therapy. Clinicians should have a high index of suspicion for
      lactic acidosis in a patient on NRTIs and the medications should be stopped at
      the earliest sign of toxicity.

PMID- 11508133
TI  - A complicated case of acute bacterial endocarditis.
AB  - Acute bacterial endocarditis continues to be a significant medical and surgical
      problem in the United States. The authors describe a complicated case of acute
      Staphylococcus aureus endocarditis in an 18-year-old man. The patient suffered
      multiple systemic emboli requiring aggressive medical and surgical intervention.

PMID- 11508134
TI  - Monoamniotic twins in a triplet gestation with favorable outcome.
AB  - BACKGROUND: Monoamniotic twins in a triplet gestation is a rare combination. Each
      condition is separately associated with significant perinatal morbidity and
      mortality. There are no data about the outcome and management of such gestations.
      CASE: We report a case of monoamniotic twins in a spontaneous dichorionic triplet
      gestation with a favorable outcome. Transvaginal ultrasound examination at nine
      weeks confirmed the diagnosis. Close follow-up was established that included
      continuous fetal monitoring after 30 weeks. At 35 weeks and after confirming
      fetal lung maturity, elective cesarean delivery was performed resulting in three
      liveborn female infants. CONCLUSION: Favorable outcome of such a rare coexistence
      of monoamniotic twins in a triplet gestation is possible. Vigilant fetal
      monitoring and timed delivery remain the mainstays of management.

PMID- 11508135
TI  - Trunks and cords of the brachial plexus, their roots and terminations.

PMID- 11508136
TI  - You need this image. GE Medical targets consumers with ad campaign for CT-PET
      scanner.

PMID- 11508137
TI  - Keeping the emphasis on safety. IOM statistics on number of medical errors
      'misleading,' JAMA report says.

PMID- 11508138
TI  - State vs. feds. Missouri becomes battleground over funding for family-planning
      programs.

PMID- 11508139
TI  - Reaping the rewards. Hospitals show their appreciation for top execs by boosting
      compensation.
AB  - Healthcare executive compensation can be a balancing act for compensation
      committees. Setting the bar too low means everyone gets a bonus, and too high
      frustrates executives with unreachable goals. Modern Healthcare's survey takes a
      look at salary trends in the past year.

PMID- 11508140
TI  - One warehousing solution. Wis. system hires manufacturer-distributor to save cash
      on supply handling.

PMID- 11508141
TI  - A for-profit surge. HCA, Tenet raise bar with robust earnings reports.

PMID- 11508142
TI  - The big breakup. Once a model of integration, Allina splits.

PMID- 11508143
TI  - Should you have your baby now?

PMID- 11508144
TI  - When dad is a donor.

PMID- 11508145
TI  - Not their mothers' choices.

PMID- 11508146
TI  - Temperatures rising.

PMID- 11508148
TI  - HHS issues first HIPAA guidance.

PMID- 11508147
TI  - Can the Web improve DM?

PMID- 11508149
TI  - 53% of physicians use Net as part of their practice.

PMID- 11508150
TI  - Make/buy/assemble? Why DM assembling is gaining ground.

PMID- 11508151
TI  - How health plans are using the Web.

PMID- 11508152
TI  - 15 things you can do tomorrow to better integrate your Web sites with your
      organization.

PMID- 11508153
TI  - [The concept of precaution in medicine].

PMID- 11508154
TI  - [Sarcoidosis and comorbidity: retrospective study of 32 cases].
AB  - PURPOSE: A retrospective study was set up to investigate active pathologic
      processes associated with sarcoidosis diagnosed in 32 patients. METHODS: Eighteen
      patients had two identified granulomatous localizations (56%) and 14 patients had
      three localizations or more (27%). Comorbidity was noticed in nine patients (28%
      of cases). Sarcoidosis was associated with an infectious disease five times
      (hepatitis C virus [HCV] infection three times, including one case after
      recombinant interferon alpha therapy, and HIV and HCV co-infection two times).
      The association of sarcoidosis with a chronic immunologic inflammatory disease
      was noticed four times (lupus erythematosus two times, myasthenia and primary
      biliary cirrhosis). Finally, in two cases sarcoidosis was associated with a
      neoplasia (non-Hodgkin's lymphoma in a co-infected HIV-HCV patient, ovarian
      cystadenocarcinoma in another patient). Sarcoidosis preceded or revealed the
      comorbidity four times.

PMID- 11508156
TI  - [Inaugural symptoms of Horton's disease in a series of 260 patients].
AB  - PURPOSE: Horton disease or 'giant cell arteritis' is a known entity in its
      typical form; the difficulty in diagnosis is due to the atypical signs and
      symptoms. METHODS: We review 260 medical files presenting Horton disease between
      1979 and 1999 in five different departments: three internal medicine departments,
      one rheumatology department and one geriatric department. RESULTS: The study
      shows a female domination with a mean age of 75 years. Temporal artery biopsy was
      done on all patients. Ten patients presented a vascular manifestation. The
      neurological manifestation was the first symptom in four patients. Five patients
      had cutaneous symptomatology, with positive temporal artery in three cases. Renal
      manifestation was present in two patients. Two symptoms are important to discuss
      because of their frequency: the cough and the peripheral arthritis. We found nine
      observations with arthritis affecting large joints and responding to nonsteroidal
      antiinflammatories with positive temporal artery biopsy in seven patients, and 21
      observations manifesting by cough without radiological signs; in 57% of cases the
      temporal artery biopsy was positive, and the cough regressed with corticoids.
      CONCLUSION: These atypical symptoms have to be known to make a diagnosis and to
      begin a corticotherapy as soon as possible.

PMID- 11508155
TI  - [Horton's disease in elderly patients aged over 75: clinical course,
      complications of corticotherapy. Comparative study of 164 patients. Towards a
      reduced initial dose].
AB  - PURPOSE: Our study compares clinical and therapeutic courses (corticosteroid
      response, corticosteroid amount, complications) in people with giant cell
      arteritis before and over 75 years, during the first year of treatment. METHODS:
      A series of 164 patients was retrospectively analysed (mean age: 73.3 years)
      among the two subgroups: before 75 and over 75 years. Patient received
      (monitoring of reduction in the corticosteroid dosage) a 240 mg intravenous bolus
      of methylprednisolone followed by 0.5 or 0.7 mg/kg/d of prednisone, or 0.7
      mg/kg/d of prednisone without the bolus. RESULTS: Corticosteroid response was
      identical for the two groups, before and over 75 (patients with
      corticoresistance: 15% vs 11.4%; NS) and giant cell arteritis-related
      complications were equivalent (n = 2 vs n = 2; NS). Corticosteroid load was
      slightly lower in the elderly group (cumulative dose of corticosteroids during
      the first year of treatment 5.2 g vs 5.8 g; P = 0.03). Patients with rheumatic
      side effects (collapses of vertebral bodies, mainly) were more frequent in the
      elderly group (15.5% vs 4.3%; P = 0.01), in spite of a limited mean follow-up
      period (10.7 months). CONCLUSION: Even if steroid response was identical in the
      therapeutic course of giant cell arteritis, rheumatic side effects appeared more
      frequent in the elderly group (over 75 years). In order to obtain a
      corticosteroid-sparing effect, new studies are necessary to evaluate a reduced
      initial dosage of corticosteroids.

PMID- 11508157
TI  - [Dengue fever: a review].
AB  - INTRODUCTION: Transmitted by Aedes mosquitoes all over the inter-tropical area,
      Dengue fever is the leading arboviral disease in humans. It is also an emerging
      disease. CURRENT KNOWLEDGE AND KEY POINTS: Increasing morbidity-mortality, and
      geographical expansion are the drastic changes noted in the recent epidemiology
      of the disease. They are related to those occurring at the bio-climatic, socio
      demographic and behavioural levels, which in turn may have led to enhanced viral
      circulation and virulence, and also vectorial resistance. The various clinical
      patterns (undifferentiated febrile episode of children, acute and algid classic
      form, the potentially fatal dengue hemorrhagic fever/dengue shock syndrome, and
      the atypical forms) are reviewed, as well as the diagnostic methods, and the
      pathogenesis (sequential infections, facilitating antibodies, capillary leakage).
      FUTURE PROSPECTS AND PROJECTS: Dengue fever is actually much more than a
      traveller's fever or an exotic curiosity. It presently threatens half the world's
      population, and remains a puzzling disease in many aspects, such as the virus
      vector and host-virus relationships, and clinical expression variability. In this
      respect, dengue fever appears as a model of viral disease. The current molecular
      approach is expected to provide us with new insights into pathophysiology, more
      efficient tools for disease control, and also an efficient vaccine in the near
      future.

PMID- 11508158
TI  - [Tumor-induced hypercalcemia. Review of bisphosphonate treatment].
AB  - INTRODUCTION: The incidence of tumor-induced hypercalcemia is between 10 to 20%.
      New treatments justify this review article. CURRENT KNOWLEDGE AND KEY POINTS:
      Tumor-induced hypercalcemia (half of all hypercalcemia) is divided into two
      groups: hematological tumors (10%), and solid tumors (90%), with osteolytic
      hypercalcemia and humoral hypercalcemia of malignancy (HHM: mediators include
      PTHrP). The two most common causes of tumor-induced hypercalcemia are lung cancer
      and breast cancer. Tumor-induced hypercalcemia most commonly disturbs
      gastrointestinal, neurological, renal and cardiovascular functions. These
      symptoms may be erroneously attributed to the underlying malignancy or its
      therapy. Prognosis of tumor-induced hypercalcemia is very poor, with median
      survival being about 3 months. Bisphosphonates have emerged as the standard
      treatment of tumor-induced hypercalcemia. The intravenous administration of
      isotonic saline is the first step in the management of tumor-induced
      hypercalcemia. Specific treatment of cancer remains essential to prevent TIH
      relapse. FUTURE PROSPECTS AND PROJECTS: New bisphosphonates have appeared, the
      most potent known bisphosphonate today is zoledronate.

PMID- 11508159
TI  - [Hashimoto encephalopathy. Analysis of four case reports].
AB  - INTRODUCTION: Encephalopathy associated with Hashimoto's thyroiditis has been
      recognized for more than 30 years and is probably underestimated. EXEGESIS: We
      report four patients with Hashimoto's thyroiditis who presented neurological or
      psychiatric features. There were three women and one man, with a mean age of 68
      years. Neurological presentations were various: seizures, psychotic episodes,
      altered consciousness, hallucinations without usual aetiological diseases
      (infectious, metabolic, neoplasic, vascular, etc.). Neurological investigations
      (EEG, brain CT, magnetic resonance imaging) were unspecific. In all cases, a
      moderately high CSF protein level without pleocytosis was found. Patients
      presented slight hypothyroidism with high titers of antithyroperoxidase
      antibodies. Despite hormone therapy replacement, neurological features persisted.
      Outcome was favorable under steroid therapy. CONCLUSION: Hashimoto's
      encephalopathy must be considered in the face of neuropsychiatric manifestations
      without obvious etiology. Pathogenic mechanisms are not clear but probably
      involve autoimmune cerebral vasculitis because of the efficacy of steroids.

PMID- 11508160
TI  - [Acute motor axonal neuropathy and aseptic meningitis due to Staphylococcus
      aureus endocarditis].
AB  - INTRODUCTION: Central nervous system complications are commonly described in
      Staphylococcus aureus endocarditis but peripheral nervous system involvement is
      rare. EXEGESIS: We report the case of a 65-year-old woman who had tetraparesia
      and aseptic meningitis revealing S. aureus endocarditis. The presence of purpura
      on the lower limbs led to an initial diagnosis of meningococcal meningitis.
      Tetraparesia was due to an acute motor axonal neuropathy. Anti-GM1 antibodies
      were negative. Meningitis and tetraparesia improved with antibiotic therapy.
      CONCLUSION: Acute motor axonal neuropathy may be a presenting symptom of S.
      aureus endocarditis.

PMID- 11508162
TI  - [The king touches you, but God heals you].

PMID- 11508161
TI  - [Acute transitory intrafamilial erythroblastopenia and hereditary spherocytosis:
      role of parvovirus B19].
AB  - INTRODUCTION: Acute parvovirus B19 infection induces a transient inhibition of
      erythroid cell formation, which may induce an erythroblastopenia crisis in
      patients suffering from chronic hemolytic anemia. EXEGESIS: We report here an
      exceptional observation of acute erythroblastopenia crisis with good outcome,
      occurring at the same time in a mother and her son, both suffering from
      hereditary spherocytosis. Diagnosis of parvovirus infection is based on detection
      of serum parvovirus B19-specific immunoglobulin M antibodies in the mother and
      her son and by the positivity of parvovirus B19 DNA detected by PCR in serum in
      the mother. Outcome was good, with the end of the erythroblastopenia crisis
      obtained 7 to 10 days later, but requiring blood transfusion in the mother.
      CONCLUSION: Our observation is a reminder that the contagiosity of parvovirus B19
      is high in household contacts and that protection of family members should
      rapidly be considered in hereditary spherocytosis.

PMID- 11508163
TI  - [Infectious endocarditis due to permanent endocavitary pacemaker lead manifested
      as hypothyroidism].

PMID- 11508164
TI  - [Pseudomembranous colitis after pristinamycin].

PMID- 11508165
TI  - [Atrophic polychondritis and aseptic meningoencephalitis].

PMID- 11508166
TI  - A shifting agenda for the public.

PMID- 11508167
TI  - Increasing longevity and future hospital use.

PMID- 11508168
TI  - AMI case-fatality data: what are the implications for Canadian hospitals?

PMID- 11508169
TI  - Through the looking glass: the cardiac care network of Ontario 10 years later.

PMID- 11508170
TI  - Conversation with Roy Romanow. Interview by Cynthia Martin.

PMID- 11508171
TI  - The economic impact of nurse staffing decisions: time to turn down another road?

PMID- 11508173
TI  - Moving toward patient-focused care.

PMID- 11508172
TI  - We're hired by the hospital, but we work for the community: examining hospital
      involvement in community action.

PMID- 11508174
TI  - A health system approach to population health.

PMID- 11508175
TI  - Stewarding the resources of patients and residents: the funding support assistant
      role at West Park Healthcare Centre.

PMID- 11508177
TI  - Canadian healthcare supply chain from revolution to evolution.

PMID- 11508178
TI  - Changes in the quality of life: a major goal of cardiac rehabilitation.
AB  - BACKGROUND: Quality of life (QOL) is a major goal in the context of preventive
      and therapeutic cardiology. In this article, quality of life concepts are
      reviewed, factors limiting QOL in cardiac disease are identified, methods of
      measurement are explored, and clinically significant changes are defined. The
      changes effected by cardiac rehabilitation are considered, together with their
      physiological and psychological correlates. A final section suggests avenues for
      future research. METHODS: Relevant articles were identified by computer
      literature searches and review of extensive personal files. FINDINGS: In the
      past, there has been an excessive focus on extending the length rather than the
      quality of the cardiac patient's life. The overall QOL is a broad concept,
      influenced by personal perceptions, coping mechanisms, and environmental
      constraints. The ideal test instrument would be reliable, valid, and responsive
      to clinical change. Potential options include a Gestalt-type instrument, a
      disease-specific instrument, a function-specific instrument, or a detailed
      generic questionnaire. There have been relatively few comparisons between these
      potential approaches. Currently, the Standard Gamble (Gestalt-type), and Living
      With Heart Failure Questionnaire (disease-specific type), and the Medical
      Outcomes Study Short-Form 36 (SF-36) Health Survey (generic-type) are among the
      most popular approaches. Problems arise in distinguishing a clinically important
      from a statistically significant change; commonly a score change of 1 standard
      error of the mean is regarded as clinically important. Correlations of scores
      with clinical, physiological, and psychological change are sometimes weak, in
      part because of floor and ceiling effects. Nevertheless, potential gains in QOL
      provide a stronger argument for preventive and therapeutic programs than do
      increases in longevity. CONCLUSIONS: The current literature supports the value of
      QOL measurements in the management of patients with cardiac disease. However,
      further research is needed to determine the optimum test instrument, and the best
      method of interpreting resultant scores.

PMID- 11508179
TI  - Enhancing adherence to prescribed exercise: structured behavioral interventions
      in clinical exercise programs.

PMID- 11508180
TI  - Clinical profile and outcomes of obese patients in cardiac rehabilitation
      stratified according to National Heart, Lung, and Blood Institute criteria.
AB  - PURPOSE: Obesity is a major health problem and must be evaluated and treated in
      cardiac rehabilitation patients. The purpose of this study was to identify the
      scope of this problem in an urban-based cardiac rehabilitation program by
      evaluating the prevalence of obesity, and comparing the clinical and risk factor
      profiles and outcomes of patients stratified according to National Heart, Lung,
      and Blood Institute (NHLBI) weight classifications. METHODS: Four hundred forty
      nine consecutive cardiac rehabilitation patients, aged 57 +/- 11 years, were
      stratified according to the NHLBI criteria as: normal (body mass index [BMI] 18
      24.9 kg/m2), overweight (BMI 25-29.9 kg/m2), class I/II obese (BMI 30-39.9
      kg/m2), and class III morbidly obese (BMI > or = 40 kg/m2). Baseline cardiac risk
      factors and dietary habits were identified, and both pre- and postexercise
      training measurements of exercise tolerance, weight, and lipid profile were
      obtained. RESULTS: Overweight and obesity (BMI > or = 25 kg/m2) were present in
      88% of patients. Compared to normal weight patients, obese patients were younger
      and had a greater adverse risk profile (higher prevalence of diabetes and
      hypertension, larger waist circumference, lower exercise capacity, lower high
      density lipoprotein cholesterol level) at entry. After 10 weeks, all groups had a
      significant increase in exercise capacity, and on average obese patients in each
      category lost weight (Class I/II--4 lbs and Class III--12 lbs). Dropout rates
      were similar among the groups. CONCLUSION: Overweight and obesity are highly
      prevalent in cardiac rehabilitation. Overweight and obese patients had a greater
      adverse cardiovascular risk profile, including a lower exercise capacity in the
      latter. Thus, targeted interventions toward weight management in contemporary
      cardiac rehabilitation programs are important. Although short-term outcomes
      appear promising, greater efforts to improve these outcomes and to support long
      term management are needed.

PMID- 11508181
TI  - Obesity: a societal and cardiovascular "malignancy".

PMID- 11508182
TI  - Assessment of functional outcomes using the 6-minute walk test in cardiac
      rehabilitation: comparison of patients with and without left ventricular
      dysfunction.

PMID- 11508183
TI  - Assessment and description of functional outcomes: a key to future success.

PMID- 11508184
TI  - Exercise training in a young adult late after a fontan procedure to repair single
      ventricle physiology.

PMID- 11508186
TI  - Public health, ethics, and human rights: a tribute to the late Jonathan Mann.

PMID- 11508185
TI  - High-intensity inspiratory muscle training in patients with chronic obstructive
      pulmonary disease and severely reduced function.
AB  - PURPOSE: This study examined the effects of inspiratory muscle training (IMT)
      with high-intensity inspiratory pressure loads on respiratory muscle performance
      and exertional dyspnea. METHODS: This was a randomized single-blind clinical
      trial. Twenty-seven patients with chronic obstructive pulmonary disease (18 men,
      9 women) with severe to very severe airflow obstruction and severely limited
      functional performance were assigned randomly to an IMT group (n = 12) or an
      educational control group (n = 15). The IMT group trained with a threshold loaded
      device for 30 minutes a day for 16 weeks using interval training techniques.
      Training was initiated with inspiratory pressure loads equal to 30% of maximal
      inspiratory pressure (Plmax) and increased as tolerated to 60% of Plmax.
      Dependent variables were measured before and after 4 months of IMT: inspiratory
      muscle strength (Plmax), respiratory muscle endurance (discontinuous incremental
      threshold loading test [DC-ITL]), dyspnea (Chronic Respiratory Disease
      Questionnaire [CRQ]), and the Borg Category-Ratio Scale ratings of perceived
      breathing difficulty (RPBD) at equal loads during the DC-ITL. RESULTS: In the IMT
      group, Plmax increased from 64 +/- 15 to 75 +/- 17 cm H2O (P < .05), performance
      on the DC-ITL test increased from a maximal load of 37 +/- 12 to 53 +/- 13 cm H2O
      (P < .05), RPBD decreased from 5.5 +/- 2.5 to 3.8 +/- 2.6 for equal loads on the
      DC-ITL (P < .05) and the CRQ Dyspnea Scale improved from 18.1 +/- 5.1 to 22.4 +/-
      5.2 (P < .05). CONCLUSIONS: Inspiratory muscle training at high-intensity loads
      significantly improved inspiratory muscle strength, respiratory muscle endurance,
      and respiratory symptoms during daily activities and respiratory exertion.

PMID- 11508187
TI  - Jonathan Mann's legacy to the 21st century: the human rights imperative for
      public health.

PMID- 11508188
TI  - A vision of health and human rights for the 21st century: a continuing discussion
      with Stephen P. Marks.

PMID- 11508189
TI  - Genetic exceptionalism vs. paradigm shift: lessons from HIV.

PMID- 11508190
TI  - What lessons can we learn from the exceptionalism debate (finally)?

PMID- 11508191
TI  - DNA patents and human dignity.

PMID- 11508192
TI  - The case for caution--being protective of human dignity in the face of corporate
      forces taking title to our DNA.

PMID- 11508193
TI  - Just what the patient ordered: the case for result-based compensation
      arrangements.

PMID- 11508194
TI  - Result-based compensation in health care: a good, but limited, idea.

PMID- 11508195
TI  - Twenty-five years after Quinlan: a review of the jurisprudence of death and
      dying.

PMID- 11508196
TI  - Frozen embryo disputes revisited: a trilogy of procreation-avoidance approaches.

PMID- 11508197
TI  - Managed care takes to the highway: implications for insureds.

PMID- 11508198
TI  - Lawsuits against IRBs: accountability or incongruity?

PMID- 11508199
TI  - Toward a theology of the community.

PMID- 11508200
TI  - Communicating during open enrollment.

PMID- 11508201
TI  - Guidelines for organizational ethics. The goal should be "virtuous organizations"
      with a "community covenant".

PMID- 11508202
TI  - Eight principles of effective governance. Effective boards need to be in place
      long before a critical decision looms.

PMID- 11508203
TI  - Sponsorship at the crossroads. Religious institutes must consider the direction
      in which they will go.

PMID- 11508204
TI  - Sponsor leadership formation. Qualifications for the next generation of sponsors.

PMID- 11508205
TI  - Toward juridic personality. The evolution of health care sponsorship continues to
      be dynamic.

PMID- 11508206
TI  - Sponsorship and the Vatican. An official describes how the church weighs
      petitions for public juridic personality.

PMID- 11508207
TI  - "Reframing" sponsorship. The time has come to make sponsorship itself a ministry.

PMID- 11508208
TI  - Effective governance in complex systems. With sponsorship at a crossroads,
      navigating change becomes vital.

PMID- 11508209
TI  - The cosponsorship model. "Five communities of relationships" are integral to the
      success of the ministry.

PMID- 11508211
TI  - New report examines employee involvement in decision making.

PMID- 11508212
TI  - HCFA: from the inside out.

PMID- 11508210
TI  - CHI marks its fifth anniversary. Shared values and a pioneer spirit unite one of
      the nation's largest not-for-profit systems.

PMID- 11508213
TI  - [Status and prospects of public health care development in the Russian
      Federation].
AB  - The article deals with topical problems of healthcare for workers in Russian
      Federation and objectives of occupational pathology service.

PMID- 11508214
TI  - [Dependence of immune and biochemical homeostasis mechanisms on lead accumulation
      in the body (experimental study)].
AB  - It was established in experiments on rats that lead accumulation in organism
      caused by 1/100 DL50 lead acetate repeated injections connected with Ca2+
      competition forcing out from bone tissue and taking it out from blood. It was
      accompanied by homeostasis maintenance physiologic mechanisms disturbance and
      lead toxic influence realization in liver, cordial, brain tissues, as well as
      immune toxic influence display on neutrophiles, periphery blood lymphocytes and
      on spleen lymphocytes.

PMID- 11508215
TI  - [Clinical and laboratory aspects concerning early detection of lead
      intoxication].
AB  - Considerable changes are induced in children by serum lead level of 0.48 mol/l
      and in adults by that of 1.42 mol/l. As these values are significantly lower than
      those considered now as safe serum lead levels, necessity is to decrease
      allowable serum lead level to 1.4 mol/l for adults and to 0.48 mol/l for
      children.

PMID- 11508216
TI  - [Neurotoxicity due to long-standing exposure to lead].
AB  - Using computer psychometric tests characterizing central nervous system
      functions, the authors proved that workers contacting lead have altered visual
      perception time, rate and accuracy of motor functions, weaker short-term memory.
      Correlation analysis revealed no relationship between the changes obtained and
      the acting concentration. Research obviously should be parallel to studies of
      health state parameters.

PMID- 11508217
TI  - [Myelopid correction of immune deficiency in staffers exposed to lead materials
      at work].
AB  - Authors demonstrated that immune dysfunction of chronic lead intoxication is
      manifested in low number and changed subpopulations of immune cells, in
      alterations of spontaneous lymphocytes proliferation. "Myelopid" corrects the
      symptoms of immune dysfunction.

PMID- 11508218
TI  - [Lead and its effects on the human body (review of literature)].

PMID- 11508219
TI  - [New hygienic requirement in work with lead].
AB  - A project "Hygienic requirements for work with lead" is specified. The project
      covers principal hygienic requirements for production (including small and
      individual enterprises) where lead is the main occupational hazard and determines
      work conditions and prophylactic measures. The authors considered new
      prophylactic approaches--average shift MAC for the air of workplace (0.05 mg/m3)
      and monitoring of serum lead level in accordance with exposure grade.

PMID- 11508220
TI  - [Classification of enterprises according to degree of accident and occupational
      disease risk].
AB  - The authors suggested approach to classification of enterprises and economy
      branches according to occupational conditions. Suggestion is to classify by means
      of quantitative methods based on claster analysis.

PMID- 11508221
TI  - [Diseases of gastro-duodenal area in workers exposed to lead].

PMID- 11508222
TI  - [Efficiency of apple pectin "medetopekt" for prophylaxis of lead incorporation in
      workers].

PMID- 11508223
TI  - [Assessing the risk of lead environmental pollution for children's health status
      in Russia].
AB  - The calculations prove that average serum lead level in children residents of
      cities with low environmental lead content approximates 10 mg/dl. This value in
      cities with high environmental lead content could be nearly 2 times higher and
      equals 18.9 mg/dl. The main lead sources influencing serum lead levels in
      children are mainly foods, the soils with dust, polluted air and drinkable waters
      play minor roles. The estimates show that nearly 400,000 children require medical
      examination and repeated measurements of serum lead levels, 10,000 children may
      need specific therapy.

PMID- 11508224
TI  - [X-ray diagnosis of lung diseases at the present technological level].

PMID- 11508225
TI  - [X-ray criteria for newly detected infiltrative pulmonary tuberculosis].
AB  - The data of examination of 334 patients with infiltrative pulmonary tuberculosis
      were analyzed. Five types of X-ray signs of the disease were identified. These
      included: 1) irregularly shaped foci formed by the fusion of foci (31.5%); 2)
      shadow areas without focal structure (35.6%); 3) round or oval foci (26.3%); 4)
      wide-walled annular ghosts (3.9%); 5) periscissurites (2.7%). A decay phase was
      detected in 51.8%. In addition to the size and pattern of an infiltrate, specific
      foci of lymphohematogenous origin play a great role in the spread of the
      infiltrate. A diversity of X-ray signs of infiltrative pulmonary tuberculosis
      makes the verification of its diagnosis difficult.

PMID- 11508226
TI  - [Differential diagnosis aspects of computerized tomography in cancer and
      tuberculosis of the lungs].
AB  - The rise in the incidence of pulmonary tuberculosis has caused an increase in the
      frequency of an association with lung neoplasms. Atypical manifestations of the
      diseases are observed in 20-22% of cases and attributable to a combination of X
      ray signs, pathomorphism in the presence of immunodeficiencies, and a particular
      mimicry of lung cancer and pulmonary tuberculosis. The paper outlines the most
      characteristic diagnostic situations which most frequently lead to erroneous
      conclusions. The conditions in this group of patients should be verified by
      invasive instrumental means to obtain a morphological material.

PMID- 11508227
TI  - [Caseous pneumonia: diagnosis, clinical aspects and treatment].
AB  - Fifty-two patients with caseous pneumonia (CP) (whose age ranged from 18 to 60
      years) admitted to a specialized tuberculosis facility of the general health care
      system were followed up. On admission, all the patients had marked intoxication
      and bronchopulmonary manifestations of the disease. X-study revealed lesions to
      one lobe in 19.2%, to 2 lobes in 32.7%, to 3 lobes or more in 48.1% of the
      patients. At the same time, all the patients had destructive changes with large
      and giants caverns in 57.7% of cases. The sputa of all 52 patients exhibited
      Mycobacteria tuberculosis (MBT), whose primary drug resistance being established.
      The nonspecific microflora composed of gram-positive cocci, gram-negative
      bacilli, fungi of the genus Candida in over 60% of patients was found in the
      sputa in two thirds of cases. A retrospective analysis indicated that CP had been
      correctly diagnosed only in 11.5% of patients within the first fortnight, in
      65.4% by the end of the first month and by the beginning of the second, and in
      23.1% following 2 months. The main reason for untimely diagnosis of CP was no
      sputum test for MBT. An algorithm of early CP diagnosis at general hospitals was
      developed, which includes a compulsory test of 3 sputum smears by the Ziehl
      Nielsen method in all patients with pneumonia on admission and 2 weeks after
      treatment with wide-spectrum antibiotics. Chemotherapy in CP patients was long
      term and combined 4-5 essential drugs within the first 4 months with obligatory
      correction after there was evidence for drug resistance. A course of nonspecific
      antibiotic therapy and a developed complex of symptomatic and pathogenetic
      treatments were compulsory. By the cessation of bacterial isolation, the
      efficiency of combined treatment was 82.7%, but a question as to a surgical
      intervention that is a compulsory component of CP therapy always arose at the
      final stage.

PMID- 11508228
TI  - [Clinical aspects, diagnosis and treatment of neurological complications of
      tuberculosis].
AB  - Data on 1112 tuberculosis patients with various neurological complications who
      were treated at Moscow Tuberculosis Clinical Hospital No. 7 during 1997-1999 are
      analyzed. A working classification of neurological complications in tuberculosis,
      which may be recommended to therapeutists, phthisiologists, and neurologists, is
      proposed. The leading neurological complications in nonspecific tuberculosis are
      described. The acute toxic encephalopathy syndrome that is characterized by a
      combination of impaired consciousness, meningeal syndrome without spinal fluid
      changes, epileptic seizures, disseminated neurological symptoms, disseminated
      intravascular coagulation syndrome, and high death rates holds the lead. Mono-
      and polyneuropathies of predominantly the lower extremities are frequently
      detectable in tuberculosis. Concomitant alcoholism, diabetes mellitus, and
      isoniazid treatment make their course poorer. Vascular abnormalities of the
      nervous system in patients with tuberculosis run much more favourably that in
      those without it. Mild forms of parkinsonism were observed in 3% of patients with
      tuberculosis, vascular dementia is detectable rarely (0.2%), strokes run without
      severe overall cerebral symptoms. The high incidence of neurological diseases in
      patients with tuberculosis requires that specialized departments of neurology
      should be set up at the institutes of tuberculosis and at multidisciplinary
      related hospitals. The tuberculosis curricula for students and postgraduate
      physicians should envisage additional sections to study diseases of the nervous
      system in tuberculosis.

PMID- 11508229
TI  - ["Therapeutic" masks of tuberculosis].

PMID- 11508230
TI  - [Neurological manifestations of tuberculosis].
AB  - One hundred and forty-four new cases of pulmonary tuberculosis were examined. The
      examination revealed the following neurological syndromes: vegetovascular
      dystonia, disseminated cerebral microsymptoms, focal lesion of the brain, sensory
      polyneuropathy. The presence of positive specific basophilic degranulation
      reactions and intracutaneous tuberculin test suggests that the body shows
      allergic reactions in response to Mycobacteria tuberculosis. And since connective
      tissue that presents in the vessels and tunics in the nervous system is involved
      into a pathological process in allergy, neurological disorders are always
      secondary in tuberculosis and due to the primary vascular wall lesion that
      following the type of secondary allergic vasculitis.

PMID- 11508231
TI  - [Effects of the enterosorbent SUMS-1 on isoniazid pharmacokinetics and lipid
      peroxidation in patients with pulmonary tuberculosis and drug-induced hepatic
      lesions].
AB  - The use of the enterosorbent SUMS-1 in the combined therapy for pulmonary
      tuberculosis patients with drug-induced toxic hepatic lesion arrests the clinical
      and laboratory manifestations of endotoxicosis, removes antibiotic intolerance,
      increases the elimination rate of isoniazid, and reduces its distribution scope,
      the area beneath the kinetic curve being unchanged. The plasma concentrations of
      primary products and after-products of lipid peroxidation products during
      enterosorbent therapy decline and the levels of ceruloplasmin and alpha
      tocopherol remain unchanged.

PMID- 11508232
TI  - [Clinical and immunological characteristics and specific features of the
      treatment of patients with recurrent sarcoidosis of respiratory organs].
AB  - In the past 35 years, the authors have followed up 5600 patients with sarcoidosis
      of respiratory organs (SRO), among whom 1.2 and 10.7% were found to have single
      and multiple recurrences. The clinical manifestations of recurrent sarcoidosis
      were moderate, by showing a drastic reduction in the count of T and T"a"
      lymphocytes, as well as helper lymphocytes, and an increase of circulating immune
      complexes and immunoglobulins G, A, and M. Poor adaptive responses (AR) defined
      by the blood leukocyte and lymphocyte counts that reflect the body's nonspecific
      responsiveness were concurrently diagnosed. In chronic recurrent SRO, poor AR as
      stress and superactivation amount to as much as 86.1%. To optimize treatment, the
      patients were given adaptogens (thymaline, levamisole, dibasole, etc.) that make
      AR better, by enhancing the efficiency of treatment, reducing its duration, and
      improving prognosis.

PMID- 11508233
TI  - [Significance of bronchospasm in the development of bronchial obstruction in
      exogenous allergic alveolitis].
AB  - In 22 patients with exogenous allergic alveolitis, VC, FVC, FEV1/VC%, PEF, MEF25,
      MEF50, MEF75 were determined before and after inhalation of berotec in 1 dose and
      antrovent in 1 dose. Bronchospasm was detected in 50% of patients. Bronchial
      spasm was the sole cause of bronchial obstruction in 18.2% of patients and a
      cause of this disorder in 31.8%. The contribution of bronchospasm to the
      development of bronchial obstruction was decisive in most patients. In 42% of
      patients, the proportion of the former in bronchial obstruction amounted to 61
      100%.

PMID- 11508234
TI  - [Morphological diagnosis of tuberculosis and some disseminated diseases of the
      lungs].
AB  - Based on the results of light optic and electron microscopic studies of lung
      tissue biopsy specimens from patients with disseminated tuberculosis (n = 31),
      sarcoidosis (n = 46), exogenous allergic alveolitis (n = 22), the authors present
      a set of various morphological signs of specific inflammation, which are
      detectable both in the area of a focus and in its adjacent sites. The set allows
      the diagnosis of the most common granulomatoses of the lung to be verified.

PMID- 11508235
TI  - [Diagnosis of tuberculosis: possibilities and limitations].

PMID- 11508237
TI  - [Automated methods of culture determination of M. tuberculosis in liquid media].
AB  - A hundred and seventy respiratory samples from patients with different forms of
      tuberculosis were used to test the efficiency of the automatic liquid culture
      systems BACTEC MGIT 960 and MB/BacT with inoculation into the standard dense
      media. All these media provided 47 M. tuberculous isolates, of them 41 (87.2%),
      38 (80.9%), and 76.6% on the BACTER 960, MB/BacT, and dense media, respectively.
      The average time of detection of mycobacterial growth by means of automatic
      systems was much shorter and equal to 10.7 days on the BACTEC 960 and 18.7 days
      on the MB/BacT versus 33.2 days on the standard dense medium. In terms of their
      sensitivity and detection rate, the automatic systems were superior to the dense
      media widely used in laboratory practice.

PMID- 11508236
TI  - [Determination of drug resistance of Mycobacterium tuberculosis by methods of
      proportions and absolute concentrations].
AB  - The studies have showed the frequency and spectrum of drug resistance, determined
      by the methods of proportions and absolute concentrations, to be virtually equal.
      This suggests that both methods are of equal diagnostic value. The method of
      absolute concentrations is rather accurate and similar to that of proportions in
      sensitivity, by ensuring comprehensive determination of the spectrum of drug
      resistance. Furthermore, the advantages of this method are its simplicity,
      accessibility, and cost-efficiency.

PMID- 11508238
TI  - [Detection of Mycobacterium tuberculosis by different methods].
AB  - Comparative assessment of the sensitivity of detection of Mycobacteria
      tuberculosis by using bacterioscopy after Ziehl-Nilsen, the cultural study on the
      Finn II yolk medium and Middlebrook 7H11 agar medium, and polymerase chain
      reaction indicated that a complex microbiological study with all available
      laboratory methods should be used.

PMID- 11508239
TI  - [Role of PCR analysis in complex bacteriological studies in phthisiology].
AB  - The study was undertaken to assess the role of polymerase chain reaction (PCR)
      analysis in complex bacteriological studies in diagnosing pulmonary tuberculosis
      in 197 patients by bacterioscopy, inoculation, and PCR. It was shown that in
      addition to conventional bacteriological methods, PCR might be used as an
      additional laboratory study in making a diagnosis in patients with restrictive
      pulmonary tuberculosis. A combination of cultural inoculation and PCR analysis
      enhances the sensitivity of bacteriological diagnosis and reduces its duration in
      oligo- and abacillary patients with tuberculosis. PCR analysis enhances the
      efficiency of laboratory control over antituberculous chemotherapy.

PMID- 11508240
TI  - [Levels of mucin-antigen 3EG5 in the blood and bronchoalveolar swabs in patients
      with tuberculosis, sarcoidosis and fibrosing alveolitis].
AB  - The levels of the antigen mucin 3EG5, a marker of the activity of interstitial
      lung diseases, were studied in the sera and bronchoalveolar swabs of patients
      with active tuberculosis, sarcoidosis of the respiratory organs, and idiopathic
      and exogenous allergic alveolitis. Its higher blood levels were detectable in
      patients with alveolitis (exogenous allergic ones to a greater extent) and absent
      in active tuberculosis and sarcoidosis. There was a correlation of the levels of
      the antigen mucin 3EG5 in the blood and bronchoalveolar swabs with the degree of
      lymphocytosis in the endopulmonal cytogram. The fact that there is a high
      variability of the blood levels of the antigen mucin 3EG5 in the range of
      nosological entities calls the differential diagnostic informative value of this
      parameter to question.

PMID- 11508241
TI  - [Antioxidant effect of laser irradiation in chronic bronchitis].
AB  - The levels of medium-weight molecules and the parameters of lipid peroxidation
      (antioxidative defence) were studied in 64 patients with chronic bronchitis (33
      with chronic pyoobstructive bronchitis and 31 with nonobstructive bronchitis).
      There was a substantial increase in the concentrations of lipid peroxides,
      malonic dialdehyde, and medium-weight molecules in the blood and a considerable
      decrease in its levels of vitamin E and the enzyme catalase. To correct the above
      disorders, the author used the conventional therapy alone or in combination with
      endobronchial laser radiation. The results of treatment, which were assessed by
      the end of 3rd and 6th weeks of its initiation, only does a combination of
      traditional therapy and laser radiation provides a balance of the lipid
      peroxidation balance--antioxidative defence followed by its stabilization by the
      end of week 6 of treatment.

PMID- 11508242
TI  - [Role of Mycoplasma infections in respiratory tract diseases].

PMID- 11508243
TI  - [Trends of WHO activities in the control of tuberculosis in Russia].

PMID- 11508245
TI  - [National Days of Laboratory Medicine in Russia-2000. II (VI) Congress of
      Clinical Laboratory Diagnosis].

PMID- 11508246
TI  - Surgical management of hepatic metastatic disease.
AB  - In Europe, liver metastases are the most common malignomas of the liver. The
      majority of metastases are due to colorectal cancer. Radical surgical resection,
      if possible, is the treatment of choice. Radical resection of metastases from
      wilms-tumor, carcinoids, carcinoma of the breast, hypernephroma, adrenal tumors,
      malignant melanoma, leiomyosarcoma and gastric cancer may improve long time
      survival, however knowledge is too small for giving general directions. Local
      destructive therapies are only beneficial when a total necrosis of the tumor is
      reached. Indications for this treatment are quite rare. Both, systemic and local
      chemotherapy offers only palliation with little influence on long time survival.
      Adjuvant and neo-adjuvant chemotherapy is applicated under study conditions with
      encouraging results. Chemoembolisation of metastases might be useful in
      individual cases.

PMID- 11508244
TI  - [Main results of implementation of the special research program "Development and
      introduction of rapid methods of diagnosis and early detection of tuberculosis,
      novel technologies in the treatment of patients with tuberculosis in various
      sites and reliable means for improving control of tuberculosis epidemiology",
      1996-2000].

PMID- 11508247
TI  - Abstracts of the 5th International Conference on Stroke and 2nd Conference of the
      Mediterranean Stroke Society. Istanbul, Turkey, March 21-24, 2001.

PMID- 11508249
TI  - Proceedings from the Uterine Contractility Symposium. Oxford, United Kingdom, May
      3, 2000.

PMID- 11508248
TI  - The mechanical action of proprioceptive length feedback in a model of cat
      hindlimb.
AB  - Postural regulation is an important part of a variety of motor tasks, including
      quiet standing and locomotion. Muscle length feedback, both the autogenic length
      feedback arising from a muscle's own spindles, and heterogenic length feedback,
      arising from its agonists and antagonists, is a strong modulator of muscle force
      and well suited to postural maintenance. The effects of this reflex feedback on 3
      D force generation and limb mechanics are not known. In this paper, we present a
      mechanical model for relating 3-D changes in cat hindlimb posture to changes in
      muscle lengths. These changes in muscle length are used to estimate changes in
      both intrinsic muscle force generation and muscle activation by length feedback
      pathways. Few muscles are found to have directly agonist mechanical actions, and
      most differ by more than 20 degrees. Endpoint force fields are largely uniform
      across the space investigated. Both autogenic and heterogenic feedback contribute
      to whole limb resistance to perturbation, autogenic pathways being most dramatic.
      Length feedback strongly reinforced a restoring force in response to endpoint
      displacement.

PMID- 11508250
TI  - Rudolf Nissen and fundoplication.

PMID- 11508251
TI  - 36th Congress of the European Society for Surgical Research (ESSR). Santiago de
      Compostela, Spain, June 6-9, 2001. Abstracts.

PMID- 11508252
TI  - Control of Verocytotoxigenic E. coli. Proceedings of a conference. September 6-8,
      2000. Oslo, Norway.

PMID- 11508253
TI  - Abstracts of the 9th International Workshop on Electrogastrography for the
      International Electrogastrography Society.

PMID- 11508254
TI  - Johann Friedrich Meckel the younger: Meckel's diverticulum.

PMID- 11508255
TI  - Proceedings of the Society for Applied Microbiology Symposium on Campylobacter,
      Helicobacter and Arcobacter. Glasgow, United Kingdom, July 2000.

PMID- 11508256
TI  - ACOG Practice Bulletin. Chronic hypertension in pregnancy. ACOG Committee on
      Practice Bulletins.
AB  - Chronic hypertension occurs in up to 5% of pregnant women; rates vary according
      to the population studied and the criteria used for confirming the diagnosis
      (1,2). This complication may result in significant maternal, fetal and neonatal
      morbidity and mortality. There has been confusion over the terminology and
      criteria used to diagnose this complication, as well as the benefit and potential
      harm of treatment during pregnancy. The purpose of this document is to review the
      effects of chronic hypertension on pregnancy, to clarify the terminology and
      criteria used to define and diagnose it during pregnancy, and to review the
      available evidence for treatment options.

PMID- 11508257
TI  - Experts taking a hard look at hospital standards. Simplifying documentation of
      standards compliance.

PMID- 11508258
TI  - Getting hospital core measures on track. The continued evolution of ORYX.

PMID- 11508259
TI  - [The coxibs, third generation of non-steroidal anti-inflammatory agents].
AB  - The coxibs, specific anti-Cox-2, represent an interesting evolution for the
      treatment of patients suffering from rheumatic conditions and presenting
      gastrointestinal ulcer risk. Anti-inflammatory effectiveness is comparable with
      the other NSAIDs, but the toxicity for the gastrointestinal mucosa is slightly
      lower. Contra-indications, extradigestive adverse effects and interactions are
      the same as for any other NSAIDs. Their risks and cost must be taken into account
      as such as the rheumatic condition of the patient. They may be prescribed to
      patients presenting a gastrointestinal risk and the relevant cost is reasonable.
      Pharmacovigilance survey at mid to long term is necessary.

PMID- 11508260
TI  - [Cholinesterase inhibitors in Alzheimer's disease].
AB  - During the last years, treatment of Alzheimer's disease has improved following a
      better detection of this disease and, more importantly, following a better
      knowledge of its physio-pathogeny. After years of aspecific symptomatic
      treatments, acetylcholinesterase inhibitors have been recently released and can
      be considered as a specific symptomatic treatment. In this pharmacologic class,
      more practical and less toxic drugs are nowadays available. Treatments of
      behavioral disturbances have also been recently improved. Nowadays we have to
      find treatments able to modify the clinical evolution and eventually prognosis of
      this disease, and even to prevent it for the patients at risk. Nevertheless a
      simplification of the prescriptions is justified, to the detriment of drugs
      without any proven activity.

PMID- 11508261
TI  - American Association of Clinical Endocrinologists 2001 Medical Guidelines for
      Clinical Practice for the Prevention and Management of Postmenopausal
      Osteoporosis.

PMID- 11508262
TI  - Visual vignette. Pituitary enlargement.

PMID- 11508263
TI  - Early cellular and molecular changes induced by diabetes in the retina.
AB  - For several decades the pathobiology of diabetic retinopathy has been the object
      of conjecture and hypotheses. Indeed, very little was known about the cellular
      events triggered by diabetes in the retina and about the processes underlying the
      microangiopathy. In the last few years there has been a concerted effort to
      acquire such information, and the work has targeted not just the retinal vessels
      but more comprehensively the retina. The picture emerging is one of multiplicity:
      multiple cell types in the retina are affected early by diabetes and multiple
      processes are operative in the microangiopathy. The main abnormalities captured
      to date are altered expression of several genes, apoptosis, microthrombosis, and
      proinflammatory changes. The new information needs to be integrated into temporal
      and mechanistic sequences and further expanded but it is beginning to provide a
      framework for the cellular dimension of diabetic retinopathy.

PMID- 11508264
TI  - Diet and risk of Type II diabetes: the role of types of fat and carbohydrate.
AB  - Although diet and nutrition are widely believed to play an important part in the
      development of Type II (non-insulin-dependent) diabetes mellitus, specific
      dietary factors have not been clearly defined. Much controversy exists about the
      relations between the amount and types of dietary fat and carbohydrate and the
      risk of diabetes. In this article, we review in detail the current evidence
      regarding the associations between different types of fats and carbohydrates and
      insulin resistance and Type II diabetes. Our findings indicate that a higher
      intake of polyunsaturated fat and possibly long-chain n-3 fatty acids could be
      beneficial, whereas a higher intake of saturated fat and trans-fat could
      adversely affect glucose metabolism and insulin resistance. In dietary practice,
      exchanging nonhydrogenated polyunsaturated fat for saturated and trans-fatty
      acids could appreciably reduce risk of Type II diabetes. In addition, a low
      glycaemic index diet with a higher amount of fiber and minimally processed whole
      grain products reduces glycaemic and insulinaemic responses and lowers the risk
      of Type II diabetes. Dietary recommendations to prevent Type II diabetes should
      focus more on the quality of fat and carbohydrate in the diet than quantity
      alone, in addition to balancing total energy intake with expenditure to avoid
      overweight and obesity.

PMID- 11508265
TI  - Enterovirus antibody levels during the first two years of life in prediabetic
      autoantibody-positive children.
AB  - AIMS/HYPOTHESIS: We evaluated the role of enterovirus infections in the
      pathogenesis of Type I (insulin-dependent) diabetes mellitus by monitoring
      enterovirus antibody levels in prediabetic children who turned positive for
      diabetes-associated autoantibodies in a prospective birth cohort study. METHODS:
      Serial serum samples taken during prospective observation starting at birth were
      analysed for IgG and IgA class antibodies against enterovirus antigens including
      purified coxsackievirus B4, echovirus 11, poliovirus 1 and a synthetic
      enterovirus peptide antigen using enzyme immunoassay. Maternal samples taken at
      the end of the third month of pregnancy were also studied. Analyses were done
      from 21 childen who developed autoantibodies and from 104 autoantibody-negative
      control children who were matched for the time of birth, gender and HLA
      susceptibility alleles. For comparison, adenovirus antibodies were also analysed
      from all samples collected. RESULTS: IgG class enterovirus antibody levels were
      high in maternal samples and in cord blood in both case and control children.
      After birth the IgG levels decreased reaching a nadir at the age of 6 months. No
      IgA class antibodies were detected at birth but started to emerge postnatally.
      Antibody levels did not differ between the autoantibody positive and the control
      children during the first 6 months of life. From 6 months to 24 months of age,
      the autoantibody positive children had higher IgG and IgA levels against
      coxsackievirus B4, echovirus 11 and the synthetic enterovirus peptide antigens
      than control children but poliovirus 1 and adenovirus antibodies were closely
      similar in the two groups. The difference between children with autoantibodies
      and control children was predominantly seen among boys and among those with the
      HLA-DQB1*0302/x genotype. CONCLUSIONS/INTERPRETATION: Our data show that children
      who seroconverted for diabetes-associated auto-antibodies develop stronger
      humoral immune responses to coxsackievirus B4, echovirus 11 and a synthetic
      enterovirus peptide antigen than children who remained negative for
      autoantibodies. Poliovirus antibodies induced by uniform vaccinations did not
      differ between the prediabetic and control children suggesting that the
      regulation of antibody responses to enteroviruses is not disturbed. Accordingly,
      the results imply a stronger enterovirus exposure in prediabetic children
      supporting the role of enteroviruses in the pathogenesis of Type I diabetes.

PMID- 11508266
TI  - Morphometric documentation of abnormal intramyocellular fat storage and reduced
      glycogen in obese patients with Type II diabetes.
AB  - AIMS/HYPOTHESIS: Insulin resistance of skeletal muscle has been associated with
      increased lipid availability. This study aimed to estimate volume fractions of
      intramyocellular triglyceride droplets and glycogen granules in skeletal muscle
      using electron microscopy and furthermore, relate these findings to insulin
      sensitivity and the level of circulating lipids. METHODS: We compared 11 obese
      patients with Type II (non-insulin-dependent) diabetes mellitus and 11 obese
      normoglycaemic subjects matched for age and sex. Glucose metabolism was
      determined using the euglycaemic hyperinsulinaemic clamp technique (40 mU.m(
      2).min(-1)) coupled with indirect calorimetry and tritiated glucose. On the
      second day, using an automatic procedure, a fasting muscle biopsy was carried out
      and processed for electron microscopy. Volume fractions of intramyocellular
      structures were estimated by pointcounting on photographic pictures in a blinded
      manner. RESULTS: Insulin-stimulated total glucose disposal rate was lower in the
      Type II diabetic subjects compared with the obese normoglycaemic subjects (4.96
      +/- 049 vs 10.35 +/- 0.89 mg.min(-1).kg ffm(-1), p < 0.001) as was glucose
      storage (2.03 +/- 0.50 vs 6.59 +/- 0.83, p < 0.001). The electron microscopy
      study revealed that the diabetic subjects had higher intramyocellular amounts of
      triglyceride (1.43 +/- 0.21 vs 0.39 +/- 0.07%, p < 0.001) and lower amounts of
      glycogen (3.53 +/- 0.33 vs 6.94 +/- 0.54%, p < 0.001). Mitochondrial volume was
      identical indicating equal aerobic capacity. The fractional intramyocellular
      lipid volume was found to be positively associated with fasting NEFA (r = 0.63, p
      = < 0.05 and r = 0.79, p = < 0.05) and triglyceride (r = 0.74, p = 0.01 and r =
      0.62, p < 0.05) in the obese diabetic and normoglycaemic cohorts respectively.
      Intramyocellular lipid content was negatively correlated to insulin sensitivity
      (r = -0.71, p < 0.02) in the obese diabetic group whereas no significant
      association was found in the obese normoglycaemic group.
      CONCLUSION/INTERPRETATION: This study shows that fat accumulates
      intramyocellulary while glycogen stores are simultaneously reduced in obese
      subjects with Type II (non-insulin-dependent) diabetes mellitus. Quantitatively,
      a major component of the excessive lipid accumulation could be secondary in
      origin, related to the diabetic state in itself, although a contribution from the
      altered insulin action cascade of obesity and diabetes cannot be excluded. In
      both groups significant positive relations were found between circulating and
      intramyocellular lipid.

PMID- 11508267
TI  - Detection of nitrotyrosine in the diabetic plasma: evidence of oxidative stress.
AB  - AIMS/HYPOTHESIS: Oxidative stress plays an important role in diabetic vascular
      complications. It has been shown that an imbalance in the ratio of nitric oxide:
      superoxide anion, because of a prevalence of superoxide anion, leads to an
      alteration in vascular reactivity. In this condition peroxynitrite production,
      resulting from the reaction between nitric oxide and superoxide, could increase.
      Peroxynitrite is responsible for nitration of tyrosine residues in proteins.
      Therefore, the presence of nitrotyrosine in plasma proteins is considered
      indirect evidence of peroxynitrite production. The aim of this study was to
      demonstrate the presence of nitrotyrosine in the plasma of patients with Type II
      (non-insulin-dependent) diabetes mellitus and to correlate its concentrations
      with the plasma concentrations of glucose and antioxidant defenses. METHODS: A
      total of 40 Type II diabetic patients and 35 healthy subjects were enrolled, and
      glycaemia, plasma nitrotyrosine, total antioxidant parameter and glycated
      haemoglobin were measured. Nitrotyrosine was detected by ELISA with a detection
      limit of 10 nmol/l. RESULTS: Nitrotyrosine was found in the plasma of all
      diabetic patients (means +/- SD = 0.251 +/- 0.141 micromol/l), whereas it was not
      detectable in the plasma of healthy control subjects. Nitrotyrosine plasma values
      were correlated with plasma glucose concentrations (r = 0.38, p < 0.02) but not
      with total antioxidant parameter or glycated haemoglobin. Total antioxidant
      parameter was reduced in diabetic patients (p < 0.01). CONCLUSIONS: The presence
      of nitrotyrosine in the plasma of diabetic patients indicates that peroxynitrite
      is generated in diabetes, suggesting a possible involvement of peroxynitrite in
      the development of diabetic complications.

PMID- 11508268
TI  - MFP14, a multifunctional emerging protein with immunomodulatory properties,
      prevents spontaneous and recurrent autoimmune diabetes in NOD mice.
AB  - AIMS/HYPOTHESIS: To test the effects of multifunctional protein 14 (MFP14), which
      shares structural homology with heat shock proteins (HSPs), on the development of
      Type I (insulin-dependent) diabetes mellitus in NOD mice. METHODS: MFP14 was
      given to euglycaemic female NOD mice from either the 4th to the 25th or from the
      12th until the 35th week, or commencing one day before islet transplantation and
      until the reappearance of hyperglycaemia. Pancreata from NOD mice treated with
      multifunctional protein 14 for 14 consecutive weeks until 18 weeks of age were
      examined histologically for insulitis. Anti-CD3 and/or lipopolysaccharide (LPS)
      induced blood levels of interferon (IFN)-gamma, interleukin (IL)-4, IL-10, IL-12
      and tumour necrosis factor (TNF)-alpha were measured by ELISA in 10 week-old
      female NOD mice treated for 6 consecutive weeks with either MFP14 or PBS. Unless
      otherwise stated, multifunctional protein 14 was administered daily 5 times a
      week at a dose of 25 microg. Control mice received PBS or, in selected
      experiments, heat-inactivated MFP14. RESULTS: MFP 14 treated mice had a
      significantly lower incidence of spontaneous diabetes compared to control mice.
      The MFP14 was equally effective both upon early and late prophylaxis and the
      protection persisted until week 50 in mice treated from weeks 4 to 25. Insulitis
      was significantly reduced by the MFP14. The MFP14 also delayed recurrence of
      hyperglycaemia in syngeneic islet-transplanted NOD mice. Although MFP14 reduced
      anti-CD3 and/or LPS-induced blood levels of IFN-gamma, TNF-alpha and IL-12 it
      increased IL-4 and IL-10. CONCLUSION/INTERPRETATION: The MFP14 could be a
      possible candidate for the prevention or early treatment of human Type I (insulin
      dependent) diabetes mellitus.

PMID- 11508269
TI  - Changing patterns of cell surface mono (ADP-ribosyl) transferase antigen ART2.2
      on resting versus cytopathically-activated T cells in NOD/Lt mice.
AB  - AIMS/HYPOTHESIS: ART2.2 is a mouse T-cell surface ectoenzyme [mono (ADP-ribosyl)
      transferase] shed upon strong activation. We analysed temporal changes in ART2.2
      expression in unmanipulated and cyclophosphamide-treated NOD/Lt mice compared
      with diabetes-resistant control strains. We used NAD, the ART2.2 substrate, to
      test whether ART-mediated ADP-ribosylation could retard diabetogenic activation
      of islet-reactive T cells in vitro. METHODS: ART2.2 and CD38, another NAD
      utilizing enzyme, were measured by flow cytometry. ADP-ribosylation from ethano
      NAD was followed by flow cytometry using a reagent specific for etheno-ADP
      ribose. RESULTS: Although mature NOD CD4 + and C D8 + T cells expressed ART2.2,
      this expression was delayed in young NOD mice when compared with control strains.
      This ontological delay at 3 weeks of age correlated with an early burst of CD25
      expression unique to NOD splenic T cells. This pattern was reproduced in
      cyclophosphamide-accelerated diabetes in young NOD/Lt males, wherein a retarded
      repopulation of ART2.2 T cells in spleen and islets correlated with development
      of heavy insulitis and diabetes. NAD inhibited anti-CD3 induced activation of
      splenic T cells in vitro and also retarded killing of beta-cell targets by NOD
      islet-reactive CD8 effectors in vitro at concentrations equal to or greater than
      1 micromol/l. Evidence suggested that CD38 on B lymphocytes competes with ART2.2
      for substrate needed by B lymphocytes for ADP ribosylation. CONCLUSIONS: ART2.2
      on T cells may not simply mark the resting state, but could also contribute to it
      via ADP-ribosylation.

PMID- 11508270
TI  - Human islet transplantation network for the treatment of Type I diabetes: first
      data from the Swiss-French GRAGIL consortium (1999-2000). Groupe de Recherche
      Rhin Rhjne Alpes Geneve pour la transplantation d'Ilots de Langerhans.
AB  - AIMS/HYPOTHESIS: Improvements in islet transplantation require clinical series
      large enough to implement controlled new strategies. The goal of this study was
      to demonstrate the feasibility of a multicentre network for islet transplantation
      in Type I (insulin-dependent) diabetic patients. METHODS: The five centres
      (Besancon, Geneva, Grenoble, Lyon, Strasbourg) of the GRAGIL network allow
      pancreas procurement, recipient recruitment, transplantation procedure and follow
      up. Islet isolation is, however, performed in one single laboratory (Geneva).
      Pancreata were procured in each of the five centres and transported to Geneva
      with an ischaemia time of less than 8 hours. Islets were isolated using a
      standard automated method. If the islet number was too low for a graft (< 6,000
      Islet-equivalent/kg), islets were cultured up to 12 days until another isolation
      was possible. Islets were transplanted by percutaneous transhepatic intraportal
      injection. Immunosuppression consisted of cyclosporine, mycophenolate mofetil,
      steroids and an anti-interleukin 2 receptor antibody. RESULTS: From March 1999 to
      June 2000, 56 pancreata procurements were performed with an average yield of
      234500 islet-equivalent, with 32 preparations over 200000 islet-equivalent. Ten C
      peptide negative Type I diabetic patients (5 men and 5 women, median age 44
      years, median diabetes duration 29 years) with an established kidney graft (> 6
      months) received 9,030 +/- 1,090 islet-equivalent/kg with a median purity of 63
      %. The number of pancreata required for each graft was 1 (n = 5) or 2 (n = 5). At
      the completion of a 12 month follow-up, we observed 0% primary nonfunction, 50%
      graft survival and 20% insulin-independence. CONCLUSIONS/INTERPRETATION: This
      study demonstrates the interest and the feasibility of a multicentre
      collaboration in human islet transplantation.

PMID- 11508271
TI  - Ambulatory blood pressure and heart rate in relation to kidney structure and
      metabolic control in adolescents with Type I diabetes.
AB  - AIMS/HYPOTHESIS: To evaluate the relationship between metabolic control, kidney
      function, ambulatory blood pressure and renal morphology in normoalbuminuric
      adolescents with Type I (insulin-dependent) diabetes mellitus. METHODS: Metabolic
      control, clearance of inulin and para-amino hippuric acid, 24 h ambulatory blood
      pressure and renal biopsies were studied in 41 patients who were 17.8 +/- 0.5
      (SEM) years of age and 10.7 +/- 0.5 years after onset of diabetes. RESULTS:
      Glomerular filtration rate and filtration fraction were higher in diabetic
      patients than in healthy control subjects. At least one third of the patients had
      systolic and nocturnal diastolic blood pressures above the 90th centile. Basement
      membrane thickness was 512 +/- 17 nm, volume fraction of mesangial matrix 10.7 +/
      0.3% and foot process width 415 +/- 6 nm. Nocturnal mean arterial blood
      pressure, adjusted for body height and gender, correlated directly to the
      basement membrane thickness, the volume fraction of mesangial matrix and the foot
      process width. Multiple regression analysis showed that HbA1c, nocturnal heart
      rate and body height account for 44% of the variations in blood pressure. HbA1c,
      nocturnal heart rate and body height explained 57% of the variation in basal
      membrane thickness, and HbA1c, nocturnal heart rate and duration of diabetes
      explained 43% of Vv(matrix/glom). Actual renal function or urinary albumin
      excretion rate had no effect. CONCLUSION/INTERPRETATION: Nocturnal heart rate and
      nocturnal blood pressure, especially the mean arterial blood pressure, seem to be
      related to glomerulopathy changes in patients in whom persistent microalbuminuria
      has not yet developed. These findings suggest that a disturbance in sympathovagal
      balance could have a pathogenic effect.

PMID- 11508272
TI  - Irbesartan normalises the deficiency in glomerular nephrin expression in a model
      of diabetes and hypertension.
AB  - AIMS/HYPOTHESIS: The location of nephrin has been identified as the slit
      diaphragm of the glomerular podocyte. Recent evidence suggests that nephrin could
      play a key role in the function of the glomerular filtration barrier and the
      development of proteinuria but its status in long-term diabetes is still not
      understood. We studied the expression of nephrin in a hypertensive model of
      diabetic nephropathy and investigated the potential influence of angiotensin II
      blockade on nephrin gene and protein expression. METHODS: Streptozotocin-diabetic
      spontaneously hypertensive rats were given either no treatment or the angiotensin
      II antagonist, irbesartan, at a dose of 15 mg/kg per day by gavage for 32 weeks.
      Non-diabetic spontaneously hypertensive rats were used as a control group. Real
      time RT-PCR and immunohistochemistry were used to assess and quantify gene and
      protein expression of nephrin. RESULTS: Diabetic spontaneously hypertensive rats
      developed albuminuria and had a reduction in both gene and protein expression of
      nephrin when compared with control rats. Irbesartan treatment prevented the
      development of albuminuria and completely abrogated the down regulation of
      nephrin in diabetic rats. CONCLUSION/INTERPRETATION: Long-term diabetes in
      spontaneously hypertensive rats is associated with a reduction in both gene and
      protein expression of nephrin within the kidney. These changes in nephrin levels
      were completely prevented by angiotensin II antagonist treatment, suggesting a
      potential novel mechanism to explain the antiproteinuric effect of agents which
      interrupt the renin-angiotensin system.

PMID- 11508274
TI  - The angiotensin II receptor antagonist candesartan cilexetil (TCV-116)
      ameliorates retinal disorders in rats.
AB  - AIMS/HYPOTHESIS: The results of the EUCLID trial (EURODIAB Controlled Trial of
      Lisinopril in Insulin-dependent Diabetes Mellitus) highlighted the importance of
      the renin-angiotensin system in the pathogenesis of diabetic retinopathy.
      Candesartan cilexetil (TCV-116), a potent angiotensin II (AII) receptor
      antagonist, has beneficial effects on hypertension as well as on heart, renal and
      cerebrovascular disease. We aimed to evaluate the effectiveness of candesarten
      cilexetil in ameliorating retinal disorders induced by hyperglycaemia. METHODS:
      We compared retinal vascular endothelial growth factor (VEGF) mRNA expression and
      the latencies of retinal oscillatory potentials in TCV-116-treated and control
      groups of stroke-prone spontaneously hypertensive rats with streptozocin (STZ)
      induced diabetes. RESULTS: Retinal VEGF mRNA expression was significantly higher
      and the latencies of oscillatory potentials were significantly elongated in STZ
      treated spontaneously hypertensive rats compared with a non-treated spontaneously
      hypertensive rat group matched for age. These changes were dependent on
      hyperglycaemia but independent of hypertension. Treatment with TCV-116 (3 mg/kg)
      significantly diminished retinal VEGF mRNA expression and the latencies of
      oscillatory potential peaks, but had no effect on plasma glucose concentrations.
      CONCLUSION/INTERPRETATION: These results suggest that TCV-116 is effective in
      preventing the development of diabetic retinopathy already in the early stages.

PMID- 11508273
TI  - Podocyte foot process broadening in experimental diabetic nephropathy:
      amelioration with renin-angiotensin blockade.
AB  - AIMS/HYPOTHESIS: Changes in podocyte number and morphology have been implicated
      in the pathogenesis of proteinuria and the progression of human and experimental
      kidney disease. This study sought to examine podocyte foot process and slit pore
      architecture in experimental diabetic nephropathy and to determine whether such
      changes were modified with renoprotective intervention by blockade of the renin
      angiotensin system. METHODS: The number of filtration slits per 100 microm of
      glomerular basement membrane was assessed by transmission electron microscopy and
      quantitated histomorphometrically in control animals and in rats with 24 weeks of
      streptozotocin-induced diabetes. Diabetic rats were either untreated or received
      the angiotensin converting enzyme inhibitor ramipril, or the angiotensin II type
      1 receptor antagonist, valsartan. RESULTS: When compared with control animals,
      diabetes was associated with a decrease in the number of slit pores per unit
      length of glomerular basement membrane, indicative of podocyte foot process
      broadening. Both ramipril and valsartan attenuated these ultrastructural changes
      to a similar degree. These differences remained after correcting for glomerular
      volume as a possible confounding variable. CONCLUSION/INTERPRETATION:
      Preservation of podocyte architecture could contribute to the renoprotective
      effects of renin-angiotensin system blockade in diabetic nephropathy.

PMID- 11508275
TI  - C-peptide prevents and improves chronic Type I diabetic polyneuropathy in the
      BB/Wor rat.
AB  - AIMS/HYPOTHESIS: Insulin and C-peptide exert neuroprotective effects and are
      deficient in Type I (insulin-dependent) diabetes mellitus but not in Type II (non
      insulin-dependent) diabetes mellitus. These studies were designed to test the
      preventive and interventional effects of C-peptide replacement on diabetic
      polyneuropathy in the Type I diabetic BB/Wor rat. METHODS: Diabetic BB/Wor rats
      were replaced with rat C-peptide from onset of diabetes and between 5 and 8
      months of diabetes. They were examined at 2 and 8 months and compared to non-C
      peptide replaced BB/Wor rats, Type II diabetic (non-C-peptide deficient) BB/Z
      rats and non-diabetic control rats. Animals were monitored as to hyperglycaemia
      and nerve conduction velocity (NCV). Acute changes such as neural Na+/K+-ATPase
      and paranodal swelling were examined at 2 months, morphometric and teased fiber
      analyses were done at 8 months. RESULTS: C-peptide replacement for 2 months in
      Type I diabetic rats prevented the acute NCV defect by 59% (p < 0.005), the
      neural Na+/K+-ATPase defect by 55% (p < 0.001) and acute paranodal swelling by
      61% (p < 0.001). Eight months of C-peptide replacement prevented the chronic
      nerve conduction defect by 71% (p < 0.001) and totally prevented axoglial
      dysjunction (p < 0.001) and paranodal demyelination (p < 0.001). C-peptide
      treatment from 5 to 8 months showed a 13% (p < 0.05) improvement in NCV, a 33% (p
      < 0.05) improvement in axoglial dysjunction, normalization (p < 0.001) of
      paranodal demyelination, repair of axonal degeneration (p < 0.01), and a fourfold
      (p < 0.001) increase in nerve fibre regeneration. CONCLUSION/INTERPRETATION: C
      peptide replacement of Type I BB/Wor-rats partially prevents acute and chronic
      metabolic, functional and structural changes that separate Type I diabetic
      polyneuropathy from its Type II counterpart suggesting that C-peptide deficiency
      plays a pathogenetic role in Type I diabetic polyneuropathy.

PMID- 11508277
TI  - S20G mutation of the amylin gene is associated with Type II diabetes in Japanese.
      Study Group of Comprehensive Analysis of Genetic Factors in Diabetes Mellitus.
AB  - AIMS/HYPOTHESIS: Amylin is a unique constituent peptide of the amyloid deposits
      found in pancreatic islets in many patients with Type II (non-insulin-dependent)
      diabetes mellitus. A previous study suggested that a missense mutation at amino
      acid 20 (AGCSer to GGCGlY), the S20G mutation, could play a role in the
      pathogenesis of early-onset Type II diabetes in Japanese people. In order to
      determine the association between the S20G mutation and Type II diabetes in the
      Japanese population, we did a large scale screening for the mutation in randomly
      selected Type II diabetic patients and non-diabetic control subjects. METHODS: We
      examined 1,538 unrelated patients with Type II diabetes and 1,108 non-diabetic
      control subjects recruited from 9 university hospitals and their affiliated
      hospitals in 7 prefectures in Japan. The presence or absence of the S20G mutation
      of the amylin gene was assessed by direct DNA sequencing or MspI RFLP analysis of
      the amplified polymerase chain reaction products of exon 3. RESULTS: The S20G
      mutation was found in 40 (2.6%) and 9 (0.8%) of the subjects in the Type II
      diabetic and the non-diabetic control groups, respectively, all present in the
      heterozygous state. The frequency of individuals with the S20G mutation is
      different between the two groups (p = 0.0007). CONCLUSION/INTERPRETATION: These
      data suggest that the S20G mutation in the amylin gene is associated with
      increased risk of development of Type II diabetes in Japanese.

PMID- 11508276
TI  - High prevalence of glucokinase mutations in Italian children with MODY. Influence
      on glucose tolerance, first-phase insulin response, insulin sensitivity and BMI.
AB  - AIMS/HYPOTHESIS: The aim of this study was to assess the prevalence of
      glucokinase gene mutations in Italian children with MODY and to investigate
      genotype/phenotype correlations of the mutants. METHODS: Screening for sequence
      variants in the glucokinase gene was performed by denaturing gradient gel
      electrophoresis and direct sequencing in 132 children with maturity onset
      diabetes of the young (MODY) and in 9 children with chronic fasting
      hyperglycaemia but without laboratory evidence for Type I (insulin-dependent)
      diabetes mellitus and with normoglycaemic parents ("non-classical" MODY).
      RESULTS: Altogether 54 mutations were identified in the MODY group (54/132 or
      41%) and 3 among the "non-classical" MODY individuals (3/9 or 33%). Paternity
      testing indicated that the latter mutations have arisen de novo. Mean fasting
      plasma glucose concentrations of the children with the mutant glucokinase was in
      the expected impaired fasting glucose range. In contrast, results of the oral
      glucose tolerance test showed a wide range from normal glucose tolerance (Group
      1: 2-h OGTT = 6.7 +/- 1.1 mmol/l; 11 patients) to diabetes (Group 2: 2-h OGTT =
      11.5 +/- 0.5 mmol/l; 9 patients), with the remaining in the impaired glucose
      tolerance range. Disruptive mutations (i.e. nonsense, frameshifts, splice-site)
      were equally represented in Groups 1 and 2 and were not clearly associated with
      an impaired first-phase insulin response. Surprisingly, 5 out of 11 children (or
      45%) in Group 1 were found to be overweight but no children in Group 2 were
      overweight. Sensitivity index (SI), calculated by a recently described method,
      was found to be significantly lower in Group 2 than in Group 1 (SI Group 2 =
      0.0013 +/- 0.0009 ml Kg(-1) min(-1)/muU/ml; SI Group 1 = 0.0068 +/- 0.0048, p <
      0.0035). CONCLUSION/INTERPRETATION: Mutations in glucokinase are the first cause
      of MODY among Italian children selected through a low threshold limit of fasting
      plasma glucose (i. e. > 5.5 mmol). The lack of correlation between the molecular
      severity of glucokinase mutations, insulin secretion at intravenous glucose
      tolerance test and differences in glucose tolerance suggests that factors outside
      the beta cell are also involved in determining post-load glucose concentrations
      in these subjects. Our results seem to indicate that the differences observed in
      the 2-h responses at the OGTT among children with MODY 2 could be related to
      individual differences in insulin sensitivity.

PMID- 11508278
TI  - Isolation and characterization of the human AKT1 gene, identification of 13
      single nucleotide polymorphisms (SNPs), and their lack of association with Type
      II diabetes.
AB  - AIMS/HYPOTHESIS: AKT1, a serine/threonine protein kinase, is an important
      downstream target of the insulin-signalling pathway, with both anti-apoptotic and
      peripheral metabolic effects. Because impaired insulin signalling is a major
      hallmark of Type II (non-insulin-dependent) diabetes mellitus, we considered
      whether the AKT1 gene could be a candidate gene involved in susceptibility of
      this condition. To test this possibility, we isolated and characterized the human
      AKT1 gene. We also looked for single nucleotide polymorphisms in the gene and
      examined their association with Type II diabetes mellitus in the Ashkenazi Jewish
      population. METHODS: Human BAC/P1 genomic libraries were screened to isolate the
      AKT1 gene. To obtain structural information and the sequences of the exon-intron
      boundaries, BAC/P1 clones were directly sequenced. Identification of single
      nucleotide polymorphisms was done by polymerase chain reaction of each exon,
      followed by denaturing high performance liquid chromatography. Six single
      nucleotide polymorphisms were genotyped in Ashkenazi Jewish patients with Type II
      diabetes mellitus and in control subjects. RESULTS: The human AKT1 gene was at
      least 24.6 kb in length and comprised 14 exons. Altogether 13 putative intragenic
      single nucleotide polymorphisms, with minor-allele frequencies ranging from 0.011
      to 0.354, were identified. The allelic and the genotypic frequencies of 6 single
      nucleotide polymorphisms were the same in diabetic patients and in control
      subjects. CONCLUSION/INTERPRETATION: The results of our studies show that the
      AKT1 gene is not a major contributor to susceptibility to Type II diabetes
      mellitus in Ashkenazi Jews.

PMID- 11508279
TI  - The accelerator hypothesis: weight gain as the missing link between Type I and
      Type II diabetes.
AB  - Blood glucose concentrations are controlled by a loop incorporating two
      components, the beta cells which secrete insulin and the insulin-sensitive
      tissues (liver, muscle, adipose) which respond to it. Loss of blood glucose
      control might result from failure of the beta cells to secrete insulin,
      resistance of the tissues to its action, or a combination of both. The
      distinctions between Type I (insulin-dependent) and Type II (non-insulin
      dependent) diabetes mellitus are becoming increasingly blurred both clinically
      and aetiologically, where beta-cell insufficiency is the shared characteristic.
      The 'Accelerator Hypothesis' identifies three processes which variably accelerate
      the loss of beta cells through apoptosis: constitution, insulin resistance and
      autoimmunity. None of the accelerators leads to diabetes without excess weight
      gain, a trend which the 'Accelerator Hypothesis' deems central to the rising
      incidence of both types of diabetes in the industrially developed world. Weight
      gain causes an increase in insulin resistance, which results in the weakening of
      glucose control. The rising blood glucose (glucotoxicity) accelerates beta-cell
      apoptosis directly in all and, by inducing beta-cell immunogens, further
      accelerates it in a subset genetically predisposed to autoimmunity. Rather than
      overlap between two types of diabetes, the 'Accelerator Hypothesis' envisages
      overlay. Body mass is central to the development and rising incidence of all
      diabetes. Only tempo distinguishes the 'types'. The control of weight gain, and
      with it insulin resistance, could be the means of minimising both.

PMID- 11508280
TI  - -to: Waldhausl W (2001) Editorial: Finally we have arrived in a new millennium.
      Diabetologia 44: 1-2.

PMID- 11508282
TI  - Maturity onset diabetes of the young (MODY) and early onset Type II diabetes are
      not caused by loss of imprinting at the transient neonatal diabetes (TNDM) locus.

PMID- 11508283
TI  - Effect of the Pro12Ala polymorphism of the PPAR-gamma2 gene on long-term weight
      change in Finnish non-diabetic subjects.

PMID- 11508284
TI  - From the Centers for Disease Control and Prevention. Delayed influenza vaccine
      availability for 2001-02 season and supplemental recommendations of the Advisory
      Committee on Immunization Practices.

PMID- 11508286
TI  - JAMA patient page. Posttraumatic stress disorder.

PMID- 11508285
TI  - From the Centers for Disease Control and Prevention. Congenital syphilis--United
      States, 2000.

PMID- 11508287
TI  - Norman Henry Ashton, CBE, DSC(Lond), FRCP, FRCS, FRCPath, FRCOphth, FRS, KSTJ
      (1913-2000).

PMID- 11508289
TI  - [Limitations and usefulness of coronary stents in diverse clinical conditions.
      Long-term course].
AB  - Since the introduction of balloon angioplasty, the acceptance and widespread
      application of coronary stents is the most important advance in interventional
      cardiology. The option of bail-out stenting has liberated interventionalists from
      the restrains of surgical stand-by. It has also allowed more aggressive balloon
      angioplasty and better short- and long-term results. This progress was enabled by
      improvements in deployment technique and antiplatelet therapy preventing most of
      the vexing problems of subacute stent thrombosis. Whereas initial registries and
      randomized trials focused on specific narrow patient populations, the clinical
      indications are broadening based on the results of new clinical trials that have
      focused on expanding populations, such as restenotic lesions, small vessels,
      total chronic occlusions, saphenous vein grafts stenoses, and acute ischemic
      syndromes. Despite this progress, a solution to the problem of in-stent
      restenosis, although less frequent than after balloon angioplasty alone, is still
      pending. In this review, we will discuss the process of restenosis which is the
      main indication for the use of stents, then we will analyze the application of
      stents in some particular clinical and anatomical situations and finally we will
      focus on in-stent restenosis which is the main limitation for stenting.

PMID- 11508288
TI  - [Elimination of carbendazim from fruit conditioning waters by adsorption on
      different materials].
AB  - The main aim of this work is to test different materials (activated carbon and
      other more "rustic" materials like clay and coal) as potential adsorbents in
      order to evaluate their adsorption capacity for carbendazime. The experiments
      were realized with certified carbendazim or with benlate solutions left to change
      long enough to suppose all the benomyl converted into carbendazim. The results
      were introduced through adsorption kinetic and isotherm forms or interpreted
      according to the Langmuir model. They pointed out that final elimination
      percentages of certified carbendazim don't exceed 55%. But even the activated
      carbon remains the most effective adsorbent, clay and coal present an interesting
      adsorption capacity, 45% for clay (but its performance is varied), 35% for coal.
      The presence of formulation additives has an inhibitive effect whatever the
      materials is. Some adsorption attempts with clay and coal mixtures (100 mg l(-1)
      of each one) were realized, there isn't a cumulative adsorption, final
      percentages of elimination are about 45%. Characterization attempts of the
      adsorbents pointed out that all the materials have a negative global surface
      charge. But clay possesses a surface charge far more negative than coal,
      sodipolary lap of carbendazim can further the adsorption. The measures of surface
      functions according to Boehm titration and capillary rising technique showed that
      coal differentiates from the other materials by its high capacity to establish
      Lifshitz-Van der Waals interactions. Carbendazim molecule can present a dipolary
      moment which could lead to the formation of hydrogen bonds. But results of
      capillary rising are to be considered by surface unities that could explain the
      superior adsorption capacity of clay (internal surface: 800m2 g(-1)).

PMID- 11508290
TI  - [Clinical, angiographic, and procedure factors predicting coronary restenosis
      after stent implantation: synthesis of the evidence].
AB  - Stent implantation is the only technique that has proven to reduce restenosis
      rate for selected lesion types after procedures of percutaneous coronary
      revascularization. Yet restenosis, although reduced, continues to exert a
      negative impact on long-term clinical outcome of treated patients. In-stent
      restenosis is almost exclusively due to neointimal hyperplasia, which appears
      more pronounced following stent than after other types of devices. A new
      revascularization procedure is clinically required in almost one half of the
      cases of in-stent restenosis; its angiographic pattern represents a major
      determinant of the efficacy of repeat intervention, a diffuse pattern being
      associated with a worse prognosis. The most powerful predictors of in-stent
      restenosis include diabetes mellitus, vessel caliber, cumulative stent length and
      its minimal lumen diameter after expansion; genetic variables and biological
      individual factors may also play an important role in conditioning the local
      response to stent placement. Intravascular ultrasound-guided stent deployment and
      the use of very high pressure to assure full stent expansion have not
      demonstrated to improve long-term clinical and angiographic results of the
      procedure. Some observational studies have suggested that plaque removal with
      directional or rotational atherectomy prior to stent implantation may reduce the
      risk of restenosis; the usefulness of this approach is currently evaluated in
      randomized clinical trials. Absence of restenosis has recently been reported in
      small pilot studies in which stents coated with antiproliferative drugs were
      used; these findings warrant further confirmation and represent one of the most
      promising issues for the next future.

PMID- 11508291
TI  - [Membrane platelet receptors and cardiovascular risk: from structure to potential
      clinical implications].
AB  - Platelets exhibit membrane receptor proteins the structure of which has adapted,
      in the course of evolution, to halt hemorrhage. These receptors are also
      implicated in thrombosis, and their structural variability is likely able to
      account for part of the variability in intraindividual susceptibility to
      thrombotic events. This review offers a summary of current knowledge on the
      molecular structure and function of platelet membrane receptors, here studied
      also in relation to the variability of platelet function in the general
      population, with the aim of discussing possible implications for the
      atherothrombotic risk.

PMID- 11508292
TI  - [Familial predisposition to ischemic cardiopathy: role of homocysteine and
      genetic polymorphism of methylenetetrahydrofolate reductase].
AB  - Homocysteine represents a risk factor for coronary artery disease determined not
      only by nutritional habits, but also by the genetic polymorphism of the enzymes
      involved in its metabolism (i.e. methylenetetrahydrofolate reductase - MTHFR).
      However, recent prospective studies questioned the initial evidence of a clear
      epidemiological and pathogenetic link between homocysteine levels and coronary
      artery disease. Moreover, the relationships between MTHFR polymorphism and
      coronary artery disease remain unclear. In this paper, the recent literature
      analyzing the role of homocysteine and MTHFR polymorphism as a risk factor for
      coronary artery disease has been reviewed.

PMID- 11508293
TI  - [Glossary of terms of management and quality].
AB  - The implementation of a quality management system (QMS) in the health-care world
      is nowadays mandatory. This is a specific request not only of local laws but also
      of the World Health Organization which recently said that "By the year 2000,
      there should be structures and processes in all member States to ensure a
      continuous improvement in the quality of health care". In addition, we are
      bombarded by demands from patients, physicians, employers and the administration.
      However a QMS is something new for the medical doctor. We think that the first
      step to divulge the culture of quality in our field is to have a good knowledge
      of the specific terminology used in the QMS. This glossary explains the meaning
      of more than 80 terms related to the QMS.

PMID- 11508294
TI  - [Rehabilitation day-hospital of the heart failure unit: structure and functions].
AB  - Chronic heart failure has emerged as an important public health problem. The
      consequent increase in the sanitary services has induced an increased consumption
      of financial resources and conditioned the need to investigate new sanitary
      models that guarantee, by integrating the inpatient and outpatient health care
      delivery, the continuity of health assistance. Cardiac rehabilitation in the
      context of a day-hospital Heart Failure Unit allows for the organization of a
      rehabilitation program including various health approaches aimed at guaranteeing
      a multidisciplinary program and the relief continuity. This article describes the
      experience developed in the Heart Failure Unit of Montescano.

PMID- 11508295
TI  - [Heart failure in nursing homes: prevalence, hospitalization, compliance to
      guidelines].
AB  - BACKGROUND: The prevalence of heart failure, the hospitalization rates for DRG
      127 and the adherence to the recommendations included in the guidelines on
      pharmacological treatment among very old persons are poorly known. METHODS: We
      screened 141 very old subjects (75% females, aged 87+/-4 years), living in 2
      nursing homes. Heart failure was defined according to clinical criteria and on
      the basis of administrative databases and chart reviews. The latter were also
      used to collect data on hospitalization rates and pharmacological therapy.
      RESULTS: We found that: 1) 23% of the subjects were affected by heart failure; 2)
      with regard to such patients, 26 hospital admissions for DRG 127 occurred in 1999
      (18 admissions and 8 readmissions; 3) ACE-inhibitors have been prescribed to 54%
      of patients with a diagnosis of heart failure. CONCLUSIONS: Heart failure affects
      a huge number of very old persons living in nursing homes. These patients have
      high hospitalization rates for DRG 127. The adherence to the recommendations
      included in the guidelines on the pharmacological therapy for very old persons is
      poor.

PMID- 11508296
TI  - [Identification of patients with acute myocardial infarction that may be
      discharged early: prospective evaluation with simple clinical and instrumental
      indicators].
AB  - BACKGROUND: The hospital stay for "uncomplicated" acute myocardial infarction
      (AMI) is often too long. A reduction in the length of hospitalization, if proven
      to be safe, is advantageous in terms of costs and health organization.
      Accordingly the aims of the present, prospective study, were to evaluate: 1) the
      patients with AMI eligible for early discharge; 2) the incidence of adverse
      cardiovascular events within 2 weeks of myocardial infarction; 3) the incidence
      of cardiovascular mortality at 6-month follow-up. METHODS: On the fifth day after
      AMI, 331 of 526 patients, consecutively admitted to our coronary care unit
      between March 1997 and August 1999, were assigned to "complicated" and
      "uncomplicated" AMI groups, according to clinical and non-invasive criteria.
      Uncomplicated myocardial infarction eligible for early discharge was defined in
      patients < 75 years, as the absence of a high risk personality, stroke, left
      bundle branch block, transient myocardial ischemia after the first 24 hours from
      AMI, clinical signs or echocardiographic evidence of left ventricular dysfunction
      (ejection fraction < 40%), ventricular fibrillation, sustained ventricular
      tachycardia, symptomatic bradyarrhythmias after the first 48 hours from AMI,
      cardioversion or defibrillation (after the first 48 hours) or the need for
      coronary angioplasty or coronary artery bypass grafting. Uncomplicated patients
      were discharged on the sixth day after AMI (hospital stay 6.5+/-0.72 days). A
      symptom-limited ergometric stress test was planned in the uncomplicated group 14
      days after AMI. "Hard" (death, reinfarction) and "non-hard" (unstable angina,
      myocardial revascularization) adverse cardiovascular events were monitored at 2
      weeks of follow-up, and cardiovascular mortality at 6-month follow-up. RESULTS:
      Four (1.2%) hard (0.3% exitus and 0.9% reinfarction) and 7 (2.1%) non-hard
      adverse events occurred among patients with uncomplicated AMI at 2 weeks of
      follow-up. Patients with uncomplicated AMI who developed adverse events,
      presented during the primary coronary event creatine kinase (CK) and CK-MB serum
      levels which were significantly lower than those observed in patients who did not
      present adverse events. In the complicated group (hospital stay 9.9+/-1.79 days),
      from day 6 to 14 after AMI, 65 (33%) hard and non-hard events occurred. A
      significant reduction in mortality between the uncomplicated and complicated
      group (2.11 vs 27.17%, p < 0.0001) was observed at 6-month follow-up.
      Multivariate analysis showed a statistically significant difference for age and
      thrombolytic treatment. CONCLUSIONS: This first Italian prospective study
      demonstrated the possibility of identifying, 5 days after AMI and on the basis of
      simple criteria and without a stress test, a low risk population of patients
      eligible for early discharge.

PMID- 11508297
TI  - [Isolated aortic valve replacement with CarboMedics mechanical prosthesis: 9-year
      clinical experience and mid-term results].
AB  - BACKGROUND: Appraisal of the medium-term results of isolated aortic valve
      replacement with a CarboMedics mechanical prosthesis. METHODS: We assessed the
      clinical data of 195 consecutive patients (mean age 59.7+/-10.9 years) operated
      on between January 1992 and June 2000. Valve disease consisted of aortic stenosis
      regurgitation in 94 patients (48.2%), isolated aortic failure in 57 (29.2%) and
      isolated stenosis in 44 (22.6%). One hundred and four patients were in NYHA
      functional class III and 25 in NYHA functional class IV Follow-up was by
      telephone interview to 100% of the patients (average follow-up 39+/-20 months).
      RESULTS: The operative mortality was 3.6% (5% in the period January 1992-December
      1995, 1.3% in the period January 1996-June 2000). Sixteen deaths occurred in the
      long term. Thus, the actuarial survivals at 36 and 72 months were 92+/-7% and
      82+/-16% respectively. In the group of survivors, 139 patients (81%) were in NYHA
      class 1,26 (15%) in NYHA class II, and 7 (4%) in NYHA class III. The freedom from
      embolic events was 96+/-3.7% and that from hemorrhagic events was 90+/-9.4%. All
      the events occurred during the first 36 months; none of the patients developed
      infections or periprosthetic leaks. CONCLUSIONS: At the medium term, the
      CarboMedics mechanical valve prosthesis appears to be reliable, with an actuarial
      survival, quality of life and incidence of morbidity comparable to those reported
      for other types of second-generation mechanical prostheses.

PMID- 11508298
TI  - [The use of evidence-based medicine data].
AB  - Although the basic concepts behind evidence-based medicine (EBM) have been
      largely accepted, some aspects regarding its theoretical background and its
      methodological characteristics and practical applications (mainly concerning the
      therapeutic choices) in daily clinical practice are still subject of debate. This
      is a real problem, and we have not yet found a fully satisfactory solution. With
      regard to the theoretical point of view, the most radical antagonists of EBM
      contest that it is an "abstract building" which has lost contact with the day-to
      day clinical reality. In spite of these criticisms, at present the medical
      community largely considers EBM as a real improvement in the methodology of
      clinical research and as a helpful support for medical practice. However, in
      applying the principles of EBM, a dangerous mistake has to be avoided: the
      meaning and benefit of EBM consist of the fact that it suggests but does not
      impose rational medical options. The practice of EBM must respect the liberty of
      the doctors and try to increase their professional and ethical responsibilities.
      These principles require wisdom and caution in drafting the guidelines generated
      by EBM and compel us to take into account some psychological side-effects of its
      diffusion among the physicians and common people.

PMID- 11508299
TI  - [Recurrent acute myocardial infarction in a patient with nocturnal paroxysmal
      hemoglobinuria].
AB  - Paroxysmal nocturnal hemoglobinuria is a form of acquired hemolytic anemia with a
      high incidence of thrombotic complications, generally in the venous district;
      arterial thrombosis is rare, and exceptional in the coronary tree. We describe
      the case of a man who had two episodes of myocardial infarction, both during a
      hemoglobinuric crisis; this patient was free from cardiovascular risk factors and
      angiography revealed that there was no coronary stenosis. The clinical course was
      favorable and the patient's response to thrombolytic and dicumarol therapy was
      satisfactory. To our knowledge, this is the second case of coronary involvement
      in paroxysmal nocturnal hemoglobinuria described in the literature.

PMID- 11508300
TI  - [Acute myocardial infarction during labor: report of a case and review of the
      literature].
AB  - Acute myocardial infarction in pregnancy is a rare condition with substantial
      risk of maternal and fetal death. There is very little information about the use
      in this setting of percutaneous coronary interventional therapy. Together with
      literature review on this topic, we present the case of a 33-year-old 39-week
      pregnant woman who sustained during labor an acute transmural anterior myocardial
      infarction. Immediately after successful cesarean section, she was treated by
      primary percutaneous coronary angioplasty and direct stenting of the left
      anterior descending coronary artery with maternal and fetal excellent outcome.

PMID- 11508301
TI  - [Effects of ACE inhibitors, calcium antagonists, and other blood-pressure
      lowering drugs: results of prospectively designed overviews of randomized
      trials].

PMID- 11508302
TI  - [Sex differences in 2-year mortality after hospital discharge for myocardial
      infarction].

PMID- 11508303
TI  - [Ticlopidine pretreatment before coronary stenting is associated with sustained
      decrease in adverse events. Data from the Evaluation of Platelets IIb/IIIa
      Inhibitor for Stenting (EPISTENT) Trial].

PMID- 11508304
TI  - [Oral amiodarone for prevention of atrial fibrillation after open heart surgery,
      the Atrial Fibrillation Suppression Trial (AFIST): a randomised placebo
      controlled trial].

PMID- 11508305
TI  - [Baroreflex sensitivity and heart rate variability in the identification of
      patients at risk for life-threatening arrhythmias: implications for clinical
      trials].

PMID- 11508306
TI  - [Heart failure in art].

PMID- 11508307
TI  - [Primary angioplasty in Florence].

PMID- 11508309
TI  - Importance of the forest canopy to fluxes of methyl mercury and total mercury to
      boreal ecosystems.
AB  - The forest canopy was an important contributor to fluxes of methyl mercury (MeHg)
      and total mercury (THg) to the forest floor of boreal uplands and wetlands and
      potentially to downstream lakes, at the Experimental Lakes Area (ELA),
      northwestern Ontario. The estimated fluxes of MeHg and THg in throughfall plus
      litterfall below the forest canopy were 2 and 3 times greater than annual fluxes
      by direct wet deposition of MeHg (0.9 mg of MeHg ha(-1)) and THg (71 mg of THg
      ha(-1)). Almost all of the increased flux of MeHg and THg under the forest canopy
      occurred as litterfall (0.14-1.3 mg of MeHg ha(-1) yr(-1) and 110-220 mg of THg
      ha(-1) yr(-1)). Throughfall added no MeHg and approximately 9 mg of THg ha(-1)
      yr(-1) to wet deposition at ELA, unlike in other regions of the world where
      atmospheric deposition was more heavily contaminated. These data suggest that dry
      deposition of Hg on foliage as an aerosol or reactive gaseous Hg (RGM) species is
      low at ELA, a finding supported by preliminary measurements of RGM there. Annual
      total deposition from throughfall and litterfall under a fire-regenerated 19-yr
      old jack pine/birch forest was 1.7 mg of MeHg ha(-1) and 200 mg of THg ha(-1). We
      found that average annual accumulation of MeHg and THg in the surficial
      litter/fungal layer of soils since the last forest fire varied between 0.6 and
      1.6 mg of MeHg ha(-1) and between 130 and 590 mg of THg ha(-1) among sites
      differing in drainage and soil moisture. When soil Hg accumulation sites were
      matched with similar sites where litterfall and throughfall were collected,
      measured fluxes of THg to the forest floor (sources) were similar to our
      estimates of longterm soil accumulation rates (sinks), suggesting that the Hg in
      litterfall and throughfall is a new and not a recycled input of Hg to forested
      ecosystems. However, further research is required to determine the proportion of
      Hg in litterfall that is being biogeochemically recycled within forest and
      wetland ecosystems and, thus, does not represent new inputs to the forest
      ecosystem.

PMID- 11508310
TI  - From the Centers for Disease Control and Prevention. Outbreak of Listeriosis
      associated with homemade Mexican-style cheese--North Carolina, October 2000
      January 2001.

PMID- 11508311
TI  - From the Centers for Disease Control and Prevention. Hepatitis B outbreak in a
      state correctional facility, 2000.

PMID- 11508312
TI  - From the Centers for Disease Control and Prevention. Vitamin A deficiency among
      children--Federated States of Micronesia, 2000.

PMID- 11508313
TI  - JAMA patient page. Doctor's orders! A more physically active life may mean a
      longer, healthier life.

PMID- 11508314
TI  - [14th Annual meeting of the Retinology Society. 22-23 June 2001, Innsbruck.
      Abstracts].

PMID- 11508315
TI  - [50th Meeting of the Association of North-German Ophthalmologists. 16-17 June
      2001, Hamburg. Abstracts].

PMID- 11508316
TI  - The American Academy for Cerebral Palsy and Developmental Medicine 55th Annual
      Meeting. Long Beach, California, USA, 2001. Abstracts.

PMID- 11508318
TI  - Estrogen markedly increases LDL-receptor activity in hypercholesterolemic
      patients.
AB  - We investigated the change in low-density lipoprotein receptor activity following
      the administration of estrogen to patients with hypercholesterolemia (HC).
      Studies were conducted in 16 patients with HC (total cholesterol (TC)>220 mg/dL)
      and 133 healthy control subjects. LDL-R activity was measured by fluorocytometry.
      Three of sixteen patients with HC showed low LDL-R activity below 80% together
      with extremely high serum levels of TC and LDL cholesterol (LDL-C). LDL-R
      activity showed an inverse correlation with serum levels of TC and LDL-C (p<0.05,
      respectively). Two women with initially low LDL-R activity who showed a marked
      increase in LDL-R activity exhibited a normalized activity at four and eight
      weeks after estriol administration, proportional to the reduction in serum levels
      of TC and LDL-C. One man with an initially extremely low LDL-R activity showed no
      abnormality at the sites of exons 7, 14, 17 and intron 12 by the PCR-DGGE method,
      which are common sites for point-mutations of LDL-R among Japanese patients with
      HC. Estrogen reduced serum levels of TC and LDL-C in patients with HC, at least
      in part, via an increase in the LDL-R activity of patients with HC and an
      initially low LDL-R activity.

PMID- 11508317
TI  - Effects of niacin-bound chromium and grape seed proanthocyanidin extract on the
      lipid profile of hypercholesterolemic subjects: a pilot study.
AB  - Hypercholesterolemia, a significant cardiovascular risk factor, is prevalent in
      the American population. Many drugs lower circulating cholesterol levels, but
      they are not infrequently associated with severe side effects. Accordingly,
      natural means to lower cholesterol levels safely would be welcomed. We examined
      40 hypercholesterolemic subjects (total cholesterol 210-300 mg/dL) in a
      randomized, double-blind, placebo-controlled study. The four groups of ten
      subjects received either placebo bid, chromium polynicotinate (Cr) 200 microg
      bid, grape seed extract (GSE) 100 mg bid, or a combination of Cr and GSE at the
      same dosage bid. Over two months, the average percent change +/- SEM in the total
      cholesterol from baseline among groups was: placebo -3.5% +/- 4, GSE -2.5% +/- 2,
      Cr -10% +/- 5, and combination -16.5% +/- 3. The decrease in the last group was
      significantly different from placebo (p < 0.01). The major decrease in
      cholesterol concentration was in the LDL levels: placebo -3.0% +/- 4, GSE -1.0%
      +/- 2.0, Cr -14% +/- 4.0, and the combination -20% +/- 6.0. Again, the
      combination of Cr and GSE significantly decreased LDL when compared to placebo
      (p<0.01). HDL levels essentially did not change among the groups. Also, there was
      no significant difference in the triglyceride concentrations among the groups;
      and no statistically significant differences were seen in the levels of
      autoantibodies to oxidized LDL (Ox-LDL). However, the trend was for the two
      groups receiving GSE to have greater decreases in the latter parameter, i.e., 
      30.7% and -44.0% in the GSE and combined groups in contrast to -17.3% and -10.4%
      in the placebo and chromium groups. We determined the number of subjects in each
      group who decreased autoantibodies to oxidized LDL greater than 50% over eight
      weeks and found these ratios among groups: placebo = 2/9, Cr = 1/10, GSE = 6/10,
      and combined = 3/8. Thus, 50% of subjects (9/18) receiving GSE had a greater than
      50% decrease in autoantibodies compared to 16% (3/19) in the two groups not
      receiving GSE. No significant changes occurred in the levels of circulating
      homocysteine and blood pressure among the four groups. We conclude that a
      combination of Cr and GSE can decrease total cholesterol and LDL levels
      significantly. Furthermore, there was a trend to decrease the circulating
      autoantibodies to oxidized LDL in the two groups receiving GSE.

PMID- 11508319
TI  - Contemplation of age-adjusted standard values of lipid profiles in Japan.
AB  - In order to establish the age-adjusted standard values of lipids in both sexes in
      Japan, we examined the plasma levels of total cholesterol, HDL-cholesterol, LDL
      cholesterol, and triglyceride levels in 1262 healthy Japanese subjects (male 616,
      female 646). LDL-cholesterol levels in women increased significantly in relation
      to menopause as it rises from 112 mg/dL in 40 year olds to 131.2 mg/dL in 50 year
      olds. Menopause seems to affect the triglyceride levels as well. These age- and
      sex-dependent changes should be considered in evaluation of patients' lipid
      profiles.

PMID- 11508320
TI  - The status of serum iron and transferrin saturation in acute non-hepatotrophic
      viral infections.
AB  - Elevation of serum iron is frequently observed in patients' with chronic
      Hepatitis C virus infection and was found to be a negative predictive factor for
      treatment response. We prospectively evaluated the iron status of 112 patients
      with acute viral infection not due to hepatitis viruses. The virus infections
      included Epstein-Barr virus (57%), cytomegalovirus (22.3%) and others (20.7%).
      Increased serum iron was documented in two patients only. Out of nine patients
      who were evaluated twice, seven had increased serum iron but the level remained
      well within the normal range. Transferrin saturation was normal in all patients.
      Disturbed liver function tests were documented in 30-40% of patients. We conclude
      that serum iron is not significantly increased during acute non (A-E) hepatitis
      viral infections with or without liver involvement.

PMID- 11508321
TI  - Study of antiangiogenic agents with possible therapeutic applications in
      neoplastic disorders and macular degeneration.
AB  - Using a previously developed method (Ambrus, et al., 1991), we found that
      pentoxifylline and thalidomide potentiate each others antiangiogenic effect
      induced by human malignant melanoma cells in the cornea of Macaca arctoides
      monkeys.

PMID- 11508322
TI  - Nutritional therapy of chronic hepatitis by whey protein (non-heated).
AB  - In an open study the clinical efficacy of milk serum (whey) protein (Immunocal;
      cysteine content: 7.6-fold higher than that of casein) isolated from fresh milk
      and purified without heating was evaluated in 25 patients with chronic hepatitis
      B or C. Immunocal (12 g as protein) food (mousse) was given twice a day, in the
      morning and evening, for 12 weeks (test period). Casein (12 g as protein) food
      (mousse) was similarly given for two weeks prior to the start of the supplement
      with Immunocal food (induction period) and for four weeks after the end of the
      supplement with Immunocal food (follow-up period). Serum alanine aminotransferase
      (ALT) activity was reduced, and plasma glutathione (GSH) levels increased in six
      and five of eight patients with chronic hepatitis B, respectively, 12 weeks after
      the start of the supplement with Immunocal food. Serum lipid peroxide levels
      significantly decreased, and interleukin (IL)-2 levels and natural killer (NK)
      activity significantly increased. However, there were no significant Immunocal
      related changes in 17 patients with chronic hepatitis C. These findings suggest
      that the long-term supplement with Immunocal alone may be effective for improving
      liver dysfunctions in patients with chronic hepatitis B.

PMID- 11508323
TI  - Fatal pancreatitis associated with systemic amyloidosis in a rheumatoid arthritis
      patient.
AB  - We report here a case of severe acute pancreatitis associated with systemic AA
      amyloidosis in a 69-year-old rheumatoid arthritis (RA) patient. AA amyloid
      deposition was detected on the walls of small pancreatic arteries and arterioles.
      The acute pancreatitis was resistant to various interventions, and acute
      necrotizing pancreatitis and multiple organ failure developed. Although AA
      amyloidosis in RA patients is rarely complicated with acute pancreatitis, acute
      pancreatitis in such cases could be severe and intractable and might result in a
      fatal outcome.

PMID- 11508324
TI  - Clinical efficacy of clenbuterol and propiverine in menopausal women with urinary
      incontinence: improvement in quality of life.
AB  - The present study evaluated the effects of clenbuterol and propiverine therapy on
      postmenopausal urinary incontinence. The patients consisted of 89 postmeopausal
      women with stress or urge incontinence who had consulted our out-patient clinic
      between March 1994 and February 1999. Patients were treated with either
      clenbuterol for stress incontinence or propiverine for urge incontinence. The
      administration period for both drugs was eight weeks. The cure rates for
      clenbuterol and propiverine were 41.2% and 52.6%, respectively. Both treatments
      significantly decreased the frequencies of incontinence, 24-h. voiding and
      nocturnal voiding, and both resulted in an overall clinical improvement.
      Furthermore, the two treatments resulted in significant subjective improvements
      in quality of life. We conclude that both medical treatments resulted in an
      improvement in urinary incontinence and contributed to overall quality of life.
      The present study demonstrated the necessity of contributed urinary incontinence
      with improvement in quality of life of postmenopausal women.

PMID- 11508325
TI  - Nuclear matrix protein (NMP) levels in patients with acute pancreatitis.
AB  - Nuclear matrix protein (NMP) is an index of apoptosis. We measured NMP in 22
      patients with acute pancreatitis and investigated the relationship between
      severity and NMP. We also measured tumor necrosis factor-alpha (TNF-alpha) and
      investigated the relationship between NMP and TNF-alpha. The NMP value increased
      significantly as the pancreatitis became more increasingly severe, and the NMP
      values were significantly higher in the group with multiple organ dysfunction
      syndrome (MODS) than in the group without MODS. A comparison of the NMP values in
      the group that survived and the group that died revealed higher NMP values in the
      former. A significant correlation was found between the NMP values and the TNF
      alpha values, suggesting that apoptosis may contribute to the pathophysiology of
      acute pancreatitis.

PMID- 11508326
TI  - A case with myasthenia gravis (MG) emerging after splenectomy for idiopathic
      thrombocytopenic purpura (ITP): possible effects of thymectomy on autoantibodies.
AB  - The combination of idiopathic thrombocytopenic purpura (ITP) and myasthenia
      gravis (MG) has been reported infrequently. We report here the development of MG
      in a patient who underwent splenectomy for ITP ten years earlier, and describe
      the serum levels of anti-acetylcholine receptor antibodies (anti-AchR) and
      platelet-associated IgG (PAIgG) followed over 11 years. The concentrations of
      both autoantibodies have been decreased after thymectomy, suggesting that this
      procedure is potentially beneficial for treating both MG and ITP.

PMID- 11508327
TI  - Enhancement of noradrenergic neural transmission: an effective therapy of
      myasthenia gravis: a report on 52 consecutive patients.
AB  - Neurochemical, neuroautonomic and neuropharmacological assessments carried out on
      all our myasthenia gravis (MG) patients showed that they presented a neural
      sympathetic deficit plus excessive adrenal-sympathetic activity. These
      abnormalities were registered during the basal (supine-resting) state, as well as
      after several stress tests (orthostasis, exercise, oral glucose and buspirone).
      In addition, MG patients showed increased levels of free-serotonin (f5HT) in the
      plasma, supposedly associated with the increased platelet aggregability which we
      found in all MG patients. As the above trio of neurochemical disorders (low
      noradrenergic-activity + high adrenergic-activity + increased f-5HT plasma
      levels) is known to favor Th-1 immunosuppression + Th-2 predominance, we outlined
      a neuropharmacological strategy for reverting the above neurochemical disorder.
      This treatment provoked sudden (acute), and late sustained improvements. Acute
      effects have been attributed to the increase of alpha-1 activity at the spinal
      motoneuron level. Late improvements always paralleled a significant normalization
      of immunological disorders. Complete normalization was registered only in non
      thymectomized MG patients.

PMID- 11508328
TI  - Mercury and selenium concentrations in maternal and neonatal scalp hair:
      relationship to amalgam-based dental treatment received during pregnancy.
AB  - Mercury and selenium concentrations were determined in scalp hair samples
      collected postpartum from 82 term pregnancy mothers and their neonates. Maternal
      mercury and selenium had median concentrations of 0.39 microg/g (range 0.1-2.13
      microg/g) and 0.75 microg/g (range 0.1-3.95 microg/g), respectively, and
      corresponding median neonatal values were 0.24 microg/g (range 0.1-1.93 microg)
      and 0.52 microg/g (range (0.1-3.0 microg/g). Amalgam-based restorative dental
      treatment received during pregnancy by 27 mothers (Group I) was associated with
      significantly higher mercury concentrations in their neonates (p < 0.0001)
      compared to those born to 55 mothers (Group II) whose most recent history of such
      dental treatment was dated to periods ranging between 1 and 12 yr prior to
      pregnancy. In the Group I mother/neonate pairs, amalgam removal and replacement
      in 10 cases was associated with significantly higher mercury concentrations
      compared to 17 cases of new amalgam emplacement. Selenium concentrations showed
      no significant intergroup differences. However, the selenium/mercury molar ratio
      values were lowest in the Group I neonates, compared to their mothers and to the
      Group II mother/neonate pairs. This ratio decreased as mercury concentration
      increased, and this interrelation was statistically significant in both groups of
      mother/neonate pairs. The data from this preliminary study suggest that amalgam
      based dental treatment during pregnancy is associated with higher prenatal
      exposure to mercury, particularly in cases of amalgam removal and replacement.
      The ability of a peripheral biological tissue, such as hair, to elicit such
      marked differences in neonatal mercury concentrations provides supporting
      evidence of high fetal susceptibility to this form of mercury exposure. The data
      are discussed in relation to the differences between maternal and fetal mercury
      metabolisms and to mercury-selenium metabolic intereactions in response to
      mercury exposure.

PMID- 11508329
TI  - Evaluation of superoxide dismutase and glutathione peroxidase enzymes and their
      cofactors in Egyptian children with Down's syndrome.
AB  - The present work investigated the activity of Cu/Zn superoxide dismutase enzyme
      (SOD) in red blood cells and glutathione peroxidase enzyme (GPx) in whole blood
      by spectrophotometric methods. Plasma levels of the cofactors copper and zinc and
      whole-blood selenium were evaluated using atomic absorption spectrophotometer.
      The study included a population of 18 Down's syndrome (DS) patients with complete
      trisomy 21 (group 1), translocations (group 2), and mosaicism (group 3), and
      their 15 matched controls. The purpose of this work was to study the gene dosage
      effect of SOD and its consequence on GPx enzyme and the various cofactors, and to
      find out correlations with developmental fields. Our results showed that in the
      population with complete trisomy 21 and translocations, SOD and GPx activities
      were increased, whereas in cases with mosaicism, the enzymes activities were
      within normal limits. Plasma copper concentrations were increased, whereas whole
      blood selenium concentrations were significantly decreased in the three DS
      groups. Plasma zinc levels were within normal in all patients. We concluded that
      changes in trace elements and enzyme activities were not related to age or sex.
      Also, there was no correlation between the enzyme levels and the developmental
      activities. Our results are useful tools for identifying nutritional status and
      guiding antioxidant intervention.

PMID- 11508331
TI  - Concentration of 17 trace elements in serum and whole blood of plains viscachas
      (Lagostomus maximus) by ICP-MS, their reference ranges, and their relation to
      cataract.
AB  - The reference ranges of the trace elements Al, As, Be, B, Cd, Co, Cu, Fe, Mn, Mo,
      Ni, Pb, Li, Rb, Se, Sr, and Zn were determined by inductively coupled plasma-mass
      spectrometry (ICP-MS) in sera of a group of free-ranging plains viscachas of the
      pampa grasslands of Argentina. The values were compared with those of a small
      group of captive plains viscachas of the Zurich Zoo with diabetes and bilateral
      cataracts. In addition, a method for digestion of whole-blood samples is
      described for the trace element determination. Significant differences in the
      concentration of trace elements in the two groups of animals are discussed. No
      correlation was found between the levels of selenium and of other trace elements
      compared to the formation of cataracts.

PMID- 11508330
TI  - Dietary boron supplementation enhances the effects of estrogen on bone mineral
      balance in ovariectomized rats.
AB  - The present study investigated whether boron would enhance the action of 17beta
      estradiol (E2) or parathyroid hormone (PTH) on bone mineral balance in
      ovariectomized (OVX) rats. Forty-three days after OVX, the rats were treated for
      5 wk with vehicle, boron (5 ppm as boric acid), E2 (30 microg/kg/d, sc), PTH (60
      microg/kg/d, sc), or a combination of boron and E2 or PTH. Bone mineral balance
      was assessed by measuring apparent absorption, excretion, and retention of
      calcium (Ca), phosphorus (P), and magnesium (Mg). Serum Ca, P, Mg, and
      osteocalcin were also measured in this experiment. Boron alone had no effects on
      food consumption, weight gain, bone mineral balance, and serum levels of Ca, P,
      Mg, and osteocalcin. E2 alone increased serum P and Mg and decreased serum
      osteocalcin, but it had no effect on bone mineral balance. The combination of
      boron and E2 markedly improved apparent absorption of Ca, P, and Mg. In addition,
      the combination treatment increased the apparent retention of Ca and Mg (but not
      P) and also increased serum Ca and Mg but not serum P. On the other hand, boron
      cotreatment did not prevent the E2-induced reduction in serum osteocalcin in OVX
      rats. PTH alone significantly increased serum Ca, P, Mg, and osteocalcin
      concentrations, although it had no effect on bone mineral balance. Contrary to
      the boron-E2 combination treatment, the combination of boron and PTH did not
      enhance bone mineral balance. However, inasmuch as boron-PTH cotreatment did not
      enhance the stimulatory action of PTH on serum Ca, P, and osteocalcin, boron
      completely abolished the stimulatory effect of PTH on serum Mg. In conclusion, we
      have demonstrated for the first time that although boron by itself has no effect
      on bone mineral homeostasis, it appears to have synergistic enhancing effects on
      the action of E2 on Ca and Mg homeostasis in OVX rats.

PMID- 11508332
TI  - High arsenic intake raises kidney copper and lowers plasma copper concentrations
      in rats.
AB  - The effect of high arsenic intake on copper metabolism was investigated. Male
      rats aged 6 wk had free access to purified diets containing either 0 or 100 mg
      As/kg diet and demineralized water for a period of 2 wk. Arsenic was added to the
      diet in the form of NaAsO2. The high-arsenic diet decreased feed and water intake
      and body weight gain, but significantly increased liver weight. Kidney weight was
      not affected. Arsenic feeding drastically elevated kidney copper concentration,
      but significantly reduced copper concentration in plasma. Both true absorption
      and biliary excretion of copper were decreased significantly in rats fed the high
      arsenic diet. True copper absorption was lowered essentially through the lower
      copper intake in the rats fed arsenic. It is speculated that arsenic feeding
      primarily leads to copper accumulation in the kidney, followed by a decrease in
      feed intake and thus in true, absolute copper absorption, a decrease in plasma
      copper concentration, and a decrease in biliary copper excretion.

PMID- 11508333
TI  - Consequences of long-term selenium-deficient diet on the prostacyclin and
      thromboxane release from rat aorta.
AB  - It is known that peroxides, which are increased during Se deficiency because of
      reduced glutathione peroxidase (GSH-Px) activity, can influence the prostacyclin
      I2/thromboxane A2 (PGI2/TXA2) ratio. In this study we analyzed the PGI2 and TXA2
      formation of aortas of long-term Se-deficient rats. Despite low GSH-Px activity
      in the Se-deficient group, the basal PGI2 and TXA2 formation was not different
      versus control animals (PGI2: 2295+/-1134 pg/mg vs 2940+/-1134 pg/mg; TXA2:
      3.83+/-1.06 pg/mg vs 5.67+/-2.99 pg/mg). However, we checked the capacity of the
      aortas of Se-deficient rats to compensate for a suddenly increased peroxide
      concentration. After peroxide stimulation, the PGI2 release was significantly
      lower in the Se-deficient group compared to the control group (PGI2: 3507+/-1829
      pg/mg vs 7986+/-2636 pg/mg). Again, the TXA2 release did not show any
      differences. The release ratio of PGI2/TXA2 decreased under peroxide stress in Se
      deficient animals. Although long-term Se deficiency showed a relatively well
      balanced metabolism under resting conditions, sudden stress, accompanied by an
      excessive radical production, cannot be compensated.

PMID- 11508334
TI  - Binding of mineral elements to locust bean gum influences availability in vitro.
AB  - Experiments were conducted to evaluate the extent to which element binding of
      locust bean gum (LBG) affects the availability of calcium, iron, and zinc in the
      gut. Infant formula was supplemented with increasing amounts of LBG and subjected
      to an intraluminal digestion procedure. Element binding was measured by
      eliminating the complexes by twofold centrifugation. Availability of the elements
      was determined using a validated continuous-flow dialysis technique. Elemental
      content of the samples, supematants, and dialysates was analyzed with validated
      atomic absorption spectrometry. LBG provided small amounts of intrinsic calcium
      (1.13+/-0.02 mg/g) and trace amounts of iron (0.02+/-0.00 mg/g) and zinc (0.01+/
      0.00 mg/g), which were strongly bound to the LBG molecule (respectively: 76.6+/
      3.3%, 83.4+/-1.2%, 96.7+/-6.6%). Correlation analysis, between percent element
      bound by LBG after centrifugation and percent trapped after dialysis, yielded
      significant correlation only for the data of zinc (r = 0.93). For calcium and
      iron, no correlation could be demonstrated; however, for iron a similar trend was
      observed. These findings suggest that element binding of LBG has a major
      influence on the availability of zinc and maybe of iron. For calcium, other
      factors might also be involved, affecting availability.

PMID- 11508335
TI  - Neurosecretory granule formation in ligated axons: additional arguments for a
      local differentiation from a Golgi apparatus extension.
AB  - The sorting domain for the different types of granules and small synaptic
      vesicles in neurosecretion is still largely a matter of debate. Some authors
      state that an exocytotic process has to precede granule formation. In previous
      studies, we favoured the idea that neurosecretory packages in terminals are
      assembled from axonal reticulum membranes simply by differentiation at the axon
      ending, the axonal reticulum being an extension of the Golgi apparatus. By
      ligating bovine splenic nerve, a de novo differentiation can be induced. After
      ligation, granules and granulo-tubular complexes appear. They were immunoreactive
      for SV2, VMAT2 and synaptobrevin II, which are all known to be highly enriched in
      large dense granules. Previously the granulo-tubular structures have already been
      recognized as precursor stadia of neurosecretory granules. It is concluded that
      at a de novo differentiation, a sorting out and aggregation is taking place of
      molecules typical for large dense granules. The small dense granules and tubules
      can be considered unripe, precursor forms of the large dense granules. All this
      occurs in the absence of signs of exocytosis. The present findings corroborate
      the view that granule formation occurs via local differentiation at an axon
      ending.

PMID- 11508336
TI  - Dystrophin-associated proteins in obliquely striated muscle of the leech
      Pontobdella muricata (Annelida, Hirudinea).
AB  - The distribution of dystrophin-associated proteins (beta-dystroglycan, alpha-,
      beta-, gamma- and delta-sarcoglycan, alpha-syntrophin and sarcospan) were studied
      in obliquely striated muscle of the leech Pontobdella muricata. Western blot
      analysis and immunohistochemical electron microscopy, using various polyclonal
      antibodies, were employed. Western blot analysis of all of these antibodies
      showed a single band, with approximately the same molecular weights as similar
      proteins detected in vertebrate muscles. The immunoelectron microscopy study
      confirmed specific immunogold labelling in the membrane of muscle cells. Since
      all dystrophin complex components have similar molecular weights and the same
      localisation in leech as in vertebrate skeletal muscle, we assume that these
      proteins have similar properties in leech and vertebrate muscle. The presence of
      these molecules in annelid muscles, together with a short version of dystrophin
      (previously described as IDLp-140) is of particular interest since phylogenetic
      and functional studies on this material could help to shed new light on the role
      and function of this complex in the muscle membrane.

PMID- 11508337
TI  - Impaired pancreatic duct-cell growth in focal areas of regeneration after partial
      pancreatectomy in the adult Goto-Kakizaki rat, a spontaneous model of non-insulin
      dependent diabetes mellitus.
AB  - The Paris colony of adult Goto-Kakizaki (GK/Par) rat, a genetic model of non
      insulin dependent diabetes mellitus, is characterized by a restriction of the
      beta-cell mass and reduced beta-cell regeneration capacity. In order to have a
      better understanding of the impaired mechanism(s) leading to reduced beta-cell
      plasticity in the GK/Par rat, we have investigated duct-cell growth capacity
      following 90% pancreatectomy, a well-defined procedure leading in non-diabetic
      rats, to sequential duct proliferation and subsequent differentiation. To this
      aim, we have performed pancreatectomy in 8-10-week-old male normoglycaemic Wistar
      and diabetic GK rats. Duct-cell proliferation and apoptosis were evaluated at
      different time points: day 0 (D0), day 2 (D2), day 7 (D7) and day 14 (D14) after
      pancreatectomy. A transient wave of duct-cell proliferation was observed on D2 in
      both small and main ducts in the pancreatectomized Wistar rats. A similar
      increase occurred in the similarly treated GK rats, but to a higher extent as
      compared to the Wistar rats. Thereafter, duct-cell proliferation from main or
      small ducts returned to non-pancreatectomized values on D7 and remained at this
      level on D14 in both the Wistar and GK pancreatectomized groups. In the common
      pancreatic duct, the number of proliferative duct-cells was higher in GK rats
      compared to Wistar on D0. In both the operated Wistar and GK rats, duct-cell
      proliferation from the common pancreatic duct similarly decreased on D2. On D7
      and D14, the same parameter returned to non-pancreatectomized values in the
      Wistar rats, while it was maintained lower in the GK rats as compared to the GK
      values on D0. In focal areas of regeneration, duct-cell proliferation was
      significantly lower in the pancreatectomized GK group compared to the age-related
      Wistar group on D7 (Wistar: 5.85+/-0.98%, GK: 3.02+/-0.69%; p < 0.01) and D14
      (Wistar: 3.82+/-0.29%, GK: 2.62+/-0.27%; ns). Only a few apoptotic duct-cells
      were observed, with no difference between the Wistar and GK groups, and that
      whatever the time after pancreatectomy and the duct category. Together, these
      results suggest that in the adult hyperglycaemic GK/Par rat facing
      pancreatectomy, duct-cell proliferation and apoptosis from the common pancreatic
      duct, main ducts and small ducts were not impaired compared to the Wistar rat.
      However, reduced duct-cell proliferation capacity in focal areas of regeneration
      in the treated GK rats probably contributes to the lower beta-cell neogenesis
      potential previously observed in this model.

PMID- 11508339
TI  - The expression of gastric H+-K+-ATPase mRNA and protein in developing rat fundic
      gland.
AB  - The proton pump H+-K+-ATPase is the final common pathway mediating the production
      and secretion of hydrochloric acid by gastric parietal cells. The present studies
      were undertaken to examine whether the expression of gastric H+-K+-ATPase mRNA
      and protein changes are associated with the development of H+-K+-ATPase activity
      in the rat fundic gland. H+-K+-ATPase activity was examined in rat fundic gland
      at different stages from gestational day 18.5 to postnatal 8 weeks. The
      expression of H+-K+-ATPase mRNA was detected by in situ hybridization using a
      digoxigenin-labelled RNA probe with a tyramide signal amplification system. The
      expression of H+-K+-ATPase protein was evaluated by immunoblotting and
      immunohistochemistry using antibodies against H+-K+-ATPase alpha- and beta
      subunits. We found that H+-K+-ATPase enzyme activity was detectable from the
      onset of gland formation (day 19.5 of gestation) and increased with age in the
      developing rat fundic gland. Expression of mRNA and protein was also discernible
      at the same time, and a progressive increase in expressions was observed as rats
      developed. Our results suggested that in developing rat fundic gland, the
      expression of both mRNA and protein of H+-K+-ATPase increased with age in a
      manner that parallels the development of H+-K+-ATPase enzyme activity.

PMID- 11508338
TI  - A comparison of caveolae and caveolin-1 to folate receptor alpha in retina and
      retinal pigment epithelium.
AB  - Caveolae are flask-shaped membrane invaginations present in most mammalian cells.
      They are distinguished by the presence of a striated coat composed of the
      protein, caveolin. Caveolae have been implicated in numerous cellular processes,
      including potocytosis in which caveolae are hypothesized to co-localize with
      folate receptor alpha and participate in folate uptake. Our laboratory has
      recently localized folate receptor alpha to the basolateral surface of the
      retinal pigment epithelium (RPE). It is present also in many other cells of the
      retina. In the present study, we asked whether caveolae were present in the RPE,
      and if so, whether their pattern of distribution was similar to folate receptor
      alpha. We also examined the distribution pattern of caveolin-1, which can be a
      marker of caveolae. Extensive electron microscopical analysis revealed caveolae
      associated with endothelial cells. However, none were detected in intact or
      cultured RPE. Laser scanning confocal microscopical analysis of intact RPE
      localized caveolin-1 to the apical and basal surfaces, a distribution unlike
      folate receptor alpha. Western analysis confirmed the presence of caveolin-1 in
      cultured RPE cells and laser scanning confocal microscopy localized the protein
      to the basal plasma membrane of the RPE, a distribution like that of folate
      receptor alpha. This distribution was confirmed by electron microscopic
      immunolocalization. The lack of caveolae in the RPE suggests that these
      structures may not be essential for folate internalization in the RPE.

PMID- 11508340
TI  - Immunohistochemical study of the phosphorylated and activated form of c-Jun NH2
      terminal kinase in human aorta.
AB  - c-Jun NH2-terminal kinase is a key enzyme mediating the cellular response to a
      variety of extracellular stimuli. In the present study, we performed
      immunohistochemical studies of the expression of the phosphorylated form of the
      kinase in 51 human aortas of various ages. The phosphorylated kinase
      immunoreactivity was strongly detected in vascular smooth muscle cells of the
      medial vessel layer of atherosclerotic lesions from adults. Immunoreactivity was
      also strongly detected in similar cells of the intima. On the other hand,
      immunoreactive phosphorylated kinase was only weakly defected in the medial
      vascular smooth muscle cells of non-atherosclerotic lesions from adults. We also
      investigated the expression of the phosphorylated kinase in infant aortas. In
      contrast to its weak immunoreactivity in adult non-atherosclerotic lesions, the
      kinase immunoreactivity was detected in high amounts in vascular smooth muscle
      cells of non-atherosclerotic lesions from infants. Thus, the abundant expression
      of the phosphorylated kinase in these cells in atherosclerotic lesions of adults
      and non-atherosclerotic lesions of infants suggests that the activation of c-Jun
      NH2-terminal kinase may be an important element initiating the proliferation of
      vascular smooth muscle cells during atherogenesis and aortic development.

PMID- 11508341
TI  - Histochemical phenotypes of von Ebner's gland of ferret and their functional
      implications.
AB  - Von Ebner's gland of ferret was examined by means of light microscopy, protein,
      mucosubstance and enzyme histochemistry, and neurohistology. Acinar cells were
      replete with granules containing neutral mucosubstances and disulphides, and
      showed strong diffuse acid phosphatase activity and weak granular staining for
      peroxidase. Staining for cytochrome oxidase, succinate dehydrogenase, and NADH
      and NAD(P)H dehydrogenases was also seen. Basolateral plasmalemma of acinar cells
      showed weak, ouabain-sensitive Na+,K+-ATPase activity. Ductal cells were of a
      simple appearance, contained thiols and showed variable staining for acid
      phosphatase, dehydrogenases and cytochrome oxidase. Variable amounts of beta
      glucuronidase reaction product were localized in the glandular parenchyma, being
      marked in atrophic areas. Prominent stellate myoepithelial cells embracing acini
      and also basal ductal cells were demonstrated by alkaline phosphatase. Thiamine
      pyrophosphatase reaction product was concentrated in blood vessels around
      parenchyma, with little Golgi-like staining in acinar cells. Acetylcholinesterase
      activity was associated with an extensive network of nerve fibres embracing
      parenchyma, whereas catecholamine fluorescence was not seen. The results suggest
      that the acini of von Ebner's gland of ferret synthesise neutral secretory
      glycoproteins and peroxidase. Water mobilization is inconspicuous. Lysosomal
      activities feature in the parenchyma, possibly a consequence of processing
      secretory products in acini, absorption in ducts and/or adaptation atrophy. The
      gland receives a rich cholinergic-type innervation, and has extensive
      myoepithelial and microvascular networks.

PMID- 11508342
TI  - Histone H3 mRNA in situ hybridization for identifying proliferating cells in
      human pancreas, with special reference to the ductal system.
AB  - In general, the incidence of proliferating cells parallels that of
      carcinogenesis. We have investigated proliferating activity and phenotype
      expression in epithelial cells in normal tissue, mucinous metaplasia and ductal
      adenocarcinoma of the pancreas. Twenty-eight resected pancreases (15 cases of
      pancreatic ductal adenocarcinoma and 13 cases of other diseases) were examined.
      Formalin-fixed, paraffin-embedded tissue sections were examined for proliferating
      cell activity using histone H3 mRNA in situ hybridization and immunostaining for
      Ki-67. In the normal pancreas, the labelling indices for proliferating cells were
      low and no generating zone was found. The following progressive increase was
      found in the labelling indices: normal ductal epithelium < mucinous metaplasia
      without papillary hyperplasia < mucinous metaplasia with papillary hyperplasia <
      ductal carcinoma. In the pancreatic ductal adenocarcinomas, the S-phase fraction,
      as defined by the ratio H3-mRNA-labelling index/Ki-67-labelling index, increased
      as the degree of differentiation decreased. Mucinous metaplasia with papillary
      hyperplasia showed organoid differentiation toward pyloric mucosa. If used in
      combination with other proliferative markers on paraffin-embedded tissue
      sections, histone H3 mRNA in situ hybridization could open broader perspectives
      on the biology of cell proliferation in the pancreatic ductal system.

PMID- 11508343
TI  - Role of receptor editing and revision in shaping the B and T lymphocyte
      repertoire.
AB  - B and T lymphocytes that carry antigen receptors are able to change specificity
      through subsequent receptor gene rearrangements. Receptor editing and receptor
      revision are terms used to distinguish those rearrangements occurring,
      respectively, in central lymphoid organs and the periphery. Secondary
      rearrangement appears to be a major player at two levels in the life of B
      lymphocytes. First, editing preserves a diverse repertoire without compromising
      self-tolerance, and revision further increases this repertoire once B cells have
      been engaged in an immune response, most likely for a better interaction with
      microbes. Recent studies have likewise suggested a role for receptor editing and
      revision in shaping the T cell repertoire during development and tolerance.

PMID- 11508344
TI  - Enhancement of endogenous corticosterone levels by a macrolide antibiotic,
      roxithromycin in mice.
AB  - The influence of roxithromycin (RXM), a macrolide antibiotic, on endogenous
      corticosterone (CS) levels was examined in BALB/c mice. Mice were sensitized
      intraperitoneally with two doses of Keyhole Limpet Hemocyanin at 1 week
      intervals. Mice were given orally 2.5 mg/kg RXM once a day for 14 days starting 7
      days after the first sensitization. RXM administration caused markedly increase
      in endogenous plasma CS levels which was peaked at 60 min after the
      administration. However, josamycin did not influence on endogenous CS levels in
      plasma. Injection of dexamethasone inhibits the plasma CS hyperproduction induced
      by RXM treatment.

PMID- 11508345
TI  - Role of plasma renin activity and the renal nerves in the natriuresis of L-NMMA
      infusion in rats.
AB  - The objective of this study was to determine the effect of N(G)-monomethyl-L
      arginine (L-NMMA) infusion on plasma renin activity (PRA) in the presence or
      absence of the renal nerves in normotensive Wistar-Kyoto (WKY) rats and Okamoto
      spontaneously hypertensive rats (SHR). All rats were unilaterally nephrectomized
      two weeks before the acute experiment. On the day of the experiment, acute renal
      denervation (Dnx) of the remaining kidney was performed in one group of WKY rats
      (Dnx-WKY; n= 10) and one group of SHRs (Dnx-SHR: n=7). The renal nerves were left
      intact in a group of WKY rats (Inn-WKY; n=8) and SHRs (Inn-SHR; n=9). After a
      control clearance period, L-NMMA was administered i.v. (15 mg/kg bolus followed
      by 500 microg/kg/min infusion) and another clearance period of 20 min was taken.
      In all experimental groups L-NMMA infusion resulted in a significant natriuresis.
      L-NMMA infusion increased fractional excretion of sodium (FE(Na)) to a greater
      extent in the Inn-SHR than in the Inn-WKY (delta FE(Na) = 5.23+/-0.87% vs delta
      FE(Na) = 2.87+/-0.73% respectively; P=0.05), PRA did not change in the SHR with
      the infusion of L-NMMA. However, in the Inn-WKY group, the natriuresis of L-NMMA
      infusion was associated with a tendency for lower PRA levels as compared to a
      group of time control Inn-WKY rats. In Dnx-WKY, the natriuresis of L-NMMA
      infusion (delta FE(Na) = 4.60+/-0.52%) was associated with a significantly lower
      level of PRA (4.26+/-1.18 ng AI/ml/hr) as compared to a group of time control Dnx
      WKY rats (9.83+/-1.32 ng AI/ml/hr; P<0.05). In the Dnx-SHR, the natriuretic
      response to L-NMMA infusion was significantly attenuated by renal denervation
      (delta FE(Na) = 2.36+/-0.34%) and PRA was unchanged. In conclusion, the
      natriuretic effect of systemic inhibition of nitric oxide (NO) synthesis was
      associated with decreased PRA in the Dnx-WKY suggesting that a potential
      interaction exists between NO and the renal nerves in the modulation of PRA in
      the normotensive WKY rat. Whereas, the natriuretic effect of L-NMMA infusion in
      the SHR in the presence and absence of the renal nerves, were independent of
      changes in PRA.

PMID- 11508346
TI  - Effect of ovarian steroids on nitric oxide synthase in the rat uterus, cervix and
      vagina.
AB  - The effects of estrogen (E2), progesterone (P) and E2 and P (E2 + P) were
      examined on nitric oxide synthase (NOS) activity in both cytosolic and
      particulate fractions isolated from the rat uterus, vagina, cervix and cerebral
      cortex. Additionally plasma nitrate + nitrite (NO3 + NO2) levels were measured in
      control and hormone treated rats. Cytosolic NOS was the predominant form being
      approximately 80% of the total in all four tissues. NOS activity in both
      fractions from all tissues was highly Ca-dependent (> 90%). Among the
      reproductive tract tissues, the highest activity was found in the cervix, which
      was nearly 5- and 2-fold higher than the uterus and vagina, respectively. NOS
      activity in the cerebral cortex was by far the highest being 5-fold higher than
      in the cervix. In contrast to the cortex, E2 treatment downregulated cytosolic
      NOS in all reproductive tract tissue, but this was statistically significant in
      only uterus. When compared with E2 treated rats, P increased cytosolic NOS in
      uterus, vagina, and particulate NOS in the cervix. The data do not give any
      indication whatsoever of differential effects of P in the uterus and cervix.

PMID- 11508347
TI  - Actions of NO donors and endogenous nitrergic transmitter on the longitudinal
      muscle of rat ileum in vitro: mechanisms involved.
AB  - The aim of this work has been to characterize and to compare the responses of the
      rat ileal longitudinal muscle to the nitric oxide (NO) donors, sodium
      nitroprusside (SNP) and morpholinosydnonimine hydrochloride (SIN-1). SNP (10(-5)
      10(-3) M) caused a contraction followed by a relaxation, both components being
      concentration-dependent. In contrast, SIN-1 (10(-5)-10(-4) M) caused a relaxation
      followed by a contraction. Neither the neural blocker tetrodotoxin (TTX) nor
      atropine were able to change the response to SNP, whereas nifedipine abolished
      its contractile component. In contrast, TTX and nifedipine diminished both the
      relaxation and the contraction in response to SIN-1, whereas atropine decreased
      only the contractile component. The specific guanylate cyclase inhibitor
      oxadiazolo-quinoxalin-1-one (ODQ) decreased the relaxation induced by SNP but did
      not modify that caused by SIN-1. The K+ channel blockers charybdotoxin, apamin
      and tetraethylamonium were unable to modify the response to SNP. In contrast,
      both TEA and apamin significantly decreased the relaxation induced by SIN- 1. The
      relaxation resulting from electrical field stimulation (EFS) of enteric nerves in
      non-adrenergic non-cholinergic conditions is mainly but not exclusively
      nitrergic, as incubation with the NO synthase inhibitor L-NNA markedly decreases
      such relaxation. EFS-induced relaxation is also sensitive to ODQ. We conclude
      that SNP acts mainly on smooth muscle cells activating L-type Ca2+ channels,
      which result in contraction, and activates the soluble guanylate cyclase, which
      results in relaxation. In contrast SIN-1 has mixed--neuronal and muscular-
      effects, the contraction being caused both by acetylcholine release from neurons
      and by direct activation of L-type Ca2+ channels on smooth muscle cells. SIN-1
      induced relaxation is cGMP-independent and it is likely to occur as a consequence
      of both, neuronal release of inhibitory transmitter(s) and by activation of
      apamin sensitive K+ channels. The effect of the nitrergic transmitter released
      from enteric nerves is different from those caused by SIN-1 but shows
      similarities with those caused by SNP.

PMID- 11508348
TI  - Antinociceptive effect following dietary-induced thiamine deficiency in mice:
      involvement of substance P and somatostatin.
AB  - We produced thiamine deficiency by treating mice with a thiamine deficient (TD)
      diet, but not with pyrithiamine, a thiamine antagonist. Twenty days after TD
      feeding, a significant antinociceptive effect was observed in the formalin test.
      A single injection of thiamine HCl (50 mg/kg, s.c.) on the 19th day after TD
      feeding (on the late TD stage) failed to reverse the antinociceptive effect, the
      muricide effect, and impairment of avoidance learning induced by TD feeding, as
      compared to pair-fed controls. These results indicate the possibility that the TD
      induced antinociceptive effect may result from irreversible changes in the spinal
      and/or brain neurons. To clarify the involvement of substance P (SP) and
      somatostatin (SST) systems in the spinal cord, we examined the effect of
      intrathecal (i.t.) injections of these agonists on TD feeding-inducd elevation of
      pain threshold. I.t. injection of SP and SST elicited a behavioral response
      consisting of reciprocal hindlimb scratching, biting and/or licking of hindpaws.
      There was no significant difference in the behavioral response to SP between TD
      mice and PF mice on the 5th day after feeding. However, on the 10th and 20th day
      after TD feeding the response to SP was significantly increased compared with PF
      mice. This phenomenon was also observed with SST on the 20th day after TD
      feeding. These results indicate the possibility that TD feeding may produce an
      increased behavioral response to SP and SST through an enhanced sensitivity of
      neurokinin-1 and SST receptors in the spinal cord. Taken together, the
      antinociceptive effect following TD feeding may result from a decrease in spinal
      SP and SST contents.

PMID- 11508349
TI  - Are adhesion molecules involved in stress-induced changes in lymphocyte
      distribution?
AB  - Acute psychological stress is associated with important changes in circulating
      cell populations and reductions in cell-mediated immune responses. However, the
      mechanisms underlying these phenomena are poorly understood. In this study, we
      investigated (i) acute and chronic restraint stress effects in Sprague-Dawley
      rats on peripheral lymphocyte subsets and (ii) adhesion molecule (beta2
      integrins) expression and (iii) also determined whether glucocorticoids could
      underlie stress-related changes in cellular redistribution. We observed time
      dependent changes in lymphocyte distribution including decreased (-21%)
      percentages of peripheral T helper cells and increased (88%) NK cell numbers
      following acute brief restraint. Acute stress was also found to overall
      upregulate beta2-integrin (CD11a and CD11b) expression on T cells and to raise
      (1049%) plasma corticosterone levels. However, this stress response was found
      habituated (-75% vs. acute) in the animals previously exposed to chronic
      restraint stress. Stress effects on circulating lymphocytes were not observed in
      animals previously exposed to chronic intermittent restraint stress or
      chronically stressed animals re-exposed to the same stressor. Our results
      indicate that 1) stress alters lymphocyte distribution, 2) that adhesion
      molecules may be involved in stress-induced alterations of T-cell distribution
      and 3) that these changes may be related to circulating glucocorticoids and
      subjected to adaptation with repeated stress exposure.

PMID- 11508350
TI  - Characteristics of depressive behavior induced by feeding thiamine-deficient diet
      in mice.
AB  - We produced thiamine-deficient (TD) mice by TD diet treatment. The growth curve
      of mice on TD feeding was sharply increased until on the 10th day and
      subsequently the body weight gradually decreased. The mortality rate in mice was
      about 67% on the 30th day after the start of TD feeding. We performed the forced
      swimming test on the 10th and 20th day after the start of TD feeding. The
      duration of immobility in the forced swimming test was increased on the 20th day
      of TD feeding. Locomotor activity and motor co-ordination between the pair-fed
      control group and TD group on the 20th day of TD feeding were not significantly
      changed. Only a single injection of thiamine HCI (50 mg/kg, s.c.) on the 10th day
      after the start of a TD diet shortened the increased duration of immobility in
      the forced swimming test on the 20th day after the start of TD feeding. Whereas
      these reversal effects of thiamine treatment on the 20th day were not found when
      the treatment was given on the 19th day after the start of a TD diet. On the 20th
      day after the start of TD feeding, the increased duration of immobility time
      induced by TD was shortened by chronic administration of the tricyclic
      antidepressant imipramine (10 mg/kg, i.p.). These results suggested that
      behavioral changes in the forced swimming test might be involved in the
      degeneration of serotonergic and noradrenergic neurons.

PMID- 11508351
TI  - Effects of anesthesia on cystometry and leak point pressure of the female rat.
AB  - Anesthetics operate by different mechanisms and are often used to perform
      urodynamics in animals. The objective of this study was to compare the effects of
      ketamine/xylazine and urethane anesthetics on filling, voiding, and leak point
      pressure (LPP) in female rats. Nineteen rats underwent awake cystometry 2 days
      after suprapubic bladder catheter implantation. Bladders were filled with saline
      (5 ml/hr), while bladder pressure was measured. Half the rats were then
      anesthetized with urethane i.p. and half were anesthetized with ketamine and
      xylazine i.p. (K/X). All rats then underwent cystometry and LPP testing under
      anesthesia. Spontaneous nonvoiding contractions were analyzed and capacity was
      determined by voiding or leakage. Capacity was significantly higher in awake rats
      (0.55 +/- 0.06 ml) than with either K/X (0.21 +/- 0.06 ml) or urethane (0.30 +/-
      0.05 ml). The pressure just prior to voiding in awake cystometry (15.6 +/- 1.7 cm
      H2O) was not significantly different from that with either anesthetic (K/X: 10.1
      +/- 1.0 cm H2O; urethane: 13.3 +/- 2.0 cm H2O). Spontaneous nonvoiding
      contractions occurred in 4 rats with urethane and 3 rats with K/X. The volume at
      which the first contraction occurred was significantly lower with K/X (0.05 +/-
      0.02 ml) than urethane (0.19 +/- 0.04 ml). There was no significant difference in
      the frequency of spontaneous nonvoiding contractions between K/X (4.58 +/-
      0.30/min) and urethane (5.16 +/- 2.66/min), nor was there a difference in LPP
      between anesthetics (K/X: 40.4 +/- 2.4 cm H2O; urethane: 36.2 +/- 3.9 cm H2O).
      The results suggest that urethane is preferable to K/X for anesthetized
      cystometry studies since it more closely simulates normal physiological
      responses.

PMID- 11508352
TI  - Inhibitory activity of nociceptin/orphanin FQ on capsaicin-induced
      bronchoconstriction in the guinea-pig.
AB  - In vivo studies were conducted in the guinea-pig to investigate the activity of
      the selective ORL1 receptor agonist nociceptin/orphanin FQ against capsaicin
      induced bronchoconstriction, a response mediated by the release of tachykinins
      from pulmonary sensory nerves. Anesthetized guinea-pigs were ventilated with a
      rodent ventilator and placed in a whole-body plethysmograph, and pulmonary
      resistance (R(L)) and dynamic lung compliance (C(Dyn)) were monitored.
      Intravenous administration of nociceptin/orphanin FQ (0.3 mg/kg) inhibited the
      capsaicin-induced bronchoconstriction. The new nonpeptide ORL1 receptor
      antagonist 1-[(3R,4R)-1-cyclooctylmethyl-3-hydroxymethyl-4-piperidyl]-3-ethyl-1,3
      dihydro-2H-benzimidazol-2-one (J-113397) administered intravenously (1 mg/kg)
      produced a significant blockade of the inhibitory effect of nociceptin/orphanin
      FQ (0.3 mg/kg) on capsaicin-induced bronchoconstriction, whereas the nonselective
      opioid receptor antagonist naloxone (1 mg/kg) had no effect. Nociceptin/orphanin
      FQ (0.3 mg/kg) did not affect the bronchoconstriction induced exogenously by the
      tachykinin NK2 receptor agonist [beta-ala8]-neurokinin A (4-10). We conclude that
      nociceptin inhibits in vivo capsaicin-evoked tachykinin release from sensory
      nerve terminals in the guinea-pig by a prejunctional mechanism. This inhibitory
      action does not involve activation of opioid receptors.

PMID- 11508354
TI  - The nerve distribution in the testis of the cat.
AB  - The autonomous innervation of the feline testis was investigated by
      immunohistochemistry and a modified acetylcholinesterase technique. The nerves
      reach the testis mainly by two routes: (1) with testicular artery and pampiniform
      plexus to the cranial extremity (funicular contribution), (2) from the epididymal
      tail to the caudal extremity (caudal contribution). Within the tunica albuginea
      the funicular contribution supplies the cranial two thirds, whereas the caudal
      third of the tunica receives its nerves via the ligamentous connection between
      testis and epididymal tail. The nerve bundles accompanying the testicular artery
      give branches to the arterial wall and the pampiniform plexus. When reaching the
      cranial testicular pole the bundles separate; the majority of them pass into the
      centrally located mediastinum testis, another large portion enters the tunica
      albuginea, particularly on its epididymal side. The septula testis are innervated
      from both sides, that is from the mediastinum and from the tunica albuginea. In
      the cat, contrary to other mammals, all septula are innervated. Furthermore,
      nerve fibers occur regularly within the testicular lobules. Generally, the
      testicular nerves of the cat are unmyelinated and mainly vascular nerves, but
      fibers are also found within the connective tissue compartments of the testis.
      The vast majority of all autonomous testicular nerves are postjunctional
      sympathetic fibers. Terminal ramifications of cholinergic fibers are exclusively
      observed in the wall of medium-sized arterioles within mediastinum, septula and
      lobuli testis. Neuropeptide Y is the most frequent peptidergic transmitter in
      feline testicular vascular plexuses. The amount of calcitonin gene-related
      peptide-positive fibers is also remarkably high in the testis, but prefers a
      location within the stroma of the tunica albuginea, mediastinum and septula. In
      the cat, Leydig cells occur not only in intertubular locations, but also as
      intratunical and mediastinal Leydig cells. In all three localizations solitary
      nerve fibers are observed between Leydig cell groups. These fibers are generally
      dopamin-beta-hydroxylase- and tyrosine hydroxylase-positive, some contain
      calcitonin gene-related peptide and, very few, substance P.

PMID- 11508353
TI  - Effects of virgin olive oil phenolics on scavenging of reactive nitrogen species
      and upon nitrergic neurotransmission.
AB  - The major phenolics from the polar fraction of virgin olive oil (caffeic acid,
      oleuropein, tyrosol and hydroxytyrosol) have well-established antioxidant
      activities but their effects on reactive nitrogen species and nitrergic
      neurotransmission have not been fully investigated. The three catechol compounds
      were active as scavengers of nitric oxide generated spontaneously from the
      decomposition of sodium nitroprusside (approximately 50% inhibition achieved at
      75 microM), and had similar ability to scavenge chemically generated
      peroxynitrite, as determined by an alpha1-antiproteinase inactivation assay
      (67.2%-92.4% reduction when added at 1 mM). Tyrosol was less active in these
      tests, but does not possess the catechol functionality. Despite their ability to
      interact with chemically prepared nitric oxide, neither oleuropein nor
      hydroxytyrosol at 5 microM altered NO*-mediated relaxations of the nerve
      stimulated rat anococcygeus preparation, but this may be because the nitrergic
      transmitter is protected from the effects of externally applied scavengers. In
      conclusion, the phenolics found in virgin olive oil possess ability to scavenge
      reactive oxygen and nitrogen species that are implicated in human pathologies,
      but their impact may be restricted to those species present in the extracellular
      environment.

PMID- 11508355
TI  - Postinflammatory changes of the diaphragmatic stomata.
AB  - Numerous investigations concerning the fine morphology of diaphragmatic stomata
      have been performed, but its ultrastructural changes in experimental conditions
      remain unclear. The present study demonstrates the peritoneal side of the
      diaphragm in adult Wistar rats by transmission electron microscopy. Ten
      experimental animals were observed 5 and 8 days after Pseudomonas aeuriginosa
      instillation (PI) into the peritoneal cavity. A control group of 6 rats showed
      flat mesothelial covering on basal lamina (BL) and connective tissue layer, as
      well as cubic mesothelial cells, single stomata over underlying lymphatic lacunae
      (LL). Five days after PI the mesothelial cells had more numerous microvilli,
      microvesicles, vacuoles, lysosomes and a lesser number of specialized contacts.
      The multiplication of the extravasal cells and larger intercellular spaces lead
      to thickenings of the connective tissue around LL. LL were larger and located in
      close proximity of the mesothelium. Intercellular spaces in the mesothelial layer
      and different types of contacts between mesothelial cells and endothelial
      protrusions of LL (with common BL or without BL) were encountered. Eight days
      after PI the mesothelium, endothelium of LL, their BL and surrounding connective
      tissue were interrupted and structurally modified to form typical new channels-
      stomata. The larger portion of the channels were formed of mesothelial cells,
      while the endothelial cells participated in the submesothelial part. LL were more
      numerous than in the previous period, and were arranged in groups. LL increased
      their vertical (50.59 microm) and horizontal (155.57 microm) diameter, as
      compared with control animals (respectively 12.37 microm and 74.08 microm).
      Neighbouring LL were separated by thin or thick septae. Peristomatal mesothelial
      cells or more rarely endothelium formed valve- or bridge-like structures. Valves
      on the opposite side of LL were observed. Groups of electron-dense bodies
      characterized some tall endothelial cells of LL. Cubic mesothelium, endothelium
      of the LL, both BL, the cell connections that formed new stomata, LL and
      surrounding connective tissue underwent rapid and parallel changes after PI.
      Among these elements of the lymphatic regions mentioned above, the mesothelium
      and endothelium of LL had a main role in experimental conditions.

PMID- 11508356
TI  - A light microscopic study of the attachment mechanism in different kinds of
      adhesive lines in rat molars.
AB  - This study was designed to observe drifting molars of 70-day-old rats by light
      microscopy, and to elucidate whether there are similar attachment mechanisms at
      different kinds of adhesive lines in periodontal mineralized tissue of the rat
      molar region. Three kinds of adhesive lines--cement lines on resorbed alveolar
      bone, cement lines on resorbed roots, and cemento-dentinal junctions were
      examined. The two kinds of cement lines showed similar histological and
      histochemical features, they were proteoglycan-rich and fiber-poor. They appeared
      to form on the resorbed tissue before principal fiber reattachment. After
      covering by new bone or by reparative cementum, the cement lines retained the
      original features. The cemento-dentinal junction showed features very similar to
      those of the cement lines. Previous studies have suggested that the cemento
      dentinal junctions bind the cementum and dentine by adhesion of proteoglycans.
      Structural similarities suggest that cement lines provide similar links between
      new bone and resorbed bone and between resorbed root and reparative cementum. In
      conclusion, this study suggests that there is one attachment mechanism for the
      different kinds of collagen based hard tissue in the rat molar region.

PMID- 11508357
TI  - Functional role and angioarchitectural arrangement of the filiform and fungiform
      papillae on the medial-dorsal surface of the beagle dog tongue.
AB  - A scanning electron microscopic study has been performed on the three-dimensional
      morphological structure and functional arrangement in microvascular cast
      specimens (MVCS) of the filiform (FiP) and fungiform papillae (FuP) of the entire
      medial-dorsal surface of the caudal portion of the beagle dog tongue. The
      characteristics and functional arrangements of each FiP and FuP were as follows:
      The FiPs densely and geometrically covered the entire medial-dorsal surface. The
      outer structure of the FiPs was composed of both the main process (mp) and
      accessory process (ap). These were formed by both the ascending and descending
      branches and originating in their tributaries was a spoon-like capillary
      micronetwork structure with a sharp arrowhead-like top. The mp inclined
      posteriorly and the ap anteriorly. On the other hand, the outer structure of the
      FuPs was a rounded papillary body composed of a capillary microvascular network
      consisting of the ascending and descending branches just as the FiPs. They were
      distributed sporadically along the oblique eines of FiPs in a V running from both
      peripheral edges in the posterocentral direction. It has been conjectured that
      the FiPs play a concentric functionally important role in transporting food and
      liquid from both the peripheral edges to the postero-central part or towards the
      pharynx, and on the other hand the FuPs play an assisting role in receiving
      gustatory sensations from the masticated food and liquid on the medial-peripheral
      and central-dorsal surface of the caudal portion of the beagle dog tongue.

PMID- 11508358
TI  - Vascular system of the human spinal cord in the prenatal period: a dye injection
      and corrosion casting study.
AB  - The vascularization of the spinal cord was investigated in 50 human fetuses aged
      from 10 to 28 gestational weeks using dye injection methods and corrosion casting
      accompanied by scanning electron microscopy. In the investigated period of fetal
      development, the general vascular architecture of the spinal cord, corresponding
      to that described postnatally, seemed to be already established. The observed
      changes included: (1) remodeling of the supplying (extrinsic) arterial branches,
      (2) transformation of the posterior anastomotic chain into two distinct posterior
      spinal arteries, and (3) development of the capillary networks in the gray and
      white matter. The remodeling of the radicular arteries supplying the spinal cord
      was accompanied by a decrease in their number and transition from regular to
      irregular distribution (appearance of intersegmental differences in their
      frequency). The anterior spinal artery and regular array of the central arteries
      were already present in the youngest fetuses examined, but the final remodeling
      of the posterior anastomotic chain into two posterior spinal arteries occurred
      between 15th and 20th week of fetal life indicating that the vascularization of
      the anterior region of the spinal cord in the investigated period of fetal life
      was more advanced as compared with that of the posterior region. The capillary
      network of the gray matter in the youngest fetuses had the form of discrete
      glomerular plexuses supplied by groups of central arteries and mainly
      vascularizing the anterior horns. Successively, the plexuses fused to form a
      continuous system along the anterior columns and the system expanded to fully
      vascularize the posterior horns. The white matter in the earlier fetal period
      seemed to be partially avascular, later the density of capillaries vascularizing
      those areas was still much lower than in the gray matter. The veins showed
      considerably greater variability than the arteries, as far as their topography
      and distribution was concerned. High tortuosity characterized the superficial
      veins, especially in the younger fetuses, although the degree of tortuosity
      differed even between individual fetuses. Only anterior spinal and central
      arteries were usually accompanied by their venous counterparts, the other veins
      seemed to have no regular topographical relations with the arteries.

PMID- 11508359
TI  - Expression of vasoactive intestinal polypeptide and calcitonin gene-related
      peptide in human stellate ganglia after acute myocardial infarction.
AB  - Using the method of indirect immunofluorescence the distribution of vasoactive
      intestinal polypeptide (VIP) and calcitonin gene-related peptide (CGRP) was
      investigated in autopsy specimens of human stellate ganglia following acute
      myocardial infarction (AMI). The dramatic increase of both VIP- and CGRP
      immunoreactivities in principal ganglionic neurons as well as of calcitonin gene
      related peptide in perineuronal nets was revealed. It was concluded that hypoxia
      and myocardial ischaemia following AMI are the main inducing factors for
      activation of both vasoactive regulatory neuropeptide synthesis. The upregulation
      of VIP and CGRP expression in sympathetic ganglionic neurons may provide
      regulatory and trophic support to the ischaemic heart.

PMID- 11508360
TI  - The development of synaptophysin immunoreactivity in the human sympathetic
      ganglia.
AB  - Using an indirect immunohistochemical method, synaptophysin immunoreactivity (SYN
      IR) has been studied in cryostat sections of stellate and thoracic ganglia in
      human fetuses, neonates, infants and adults. In the course of development, a
      progressive increase in SYN-IR in axonal terminals and around nerve cells was
      demonstrated. In contrast, large clusters of small intensely fluorescent (SIF)
      cells and paraganglionic cells increased in number in fetuses and premature
      neonates at 24-25 weeks. Such SIF cell clusters varied in form and often occurred
      at pole or subcapsular areas of sympathetic ganglia close to blood vessels or
      paraganglia. With increasing gestational age and during infancy, a decrease in
      sizes of SIF cell groups and paraganglionic cells as well as changes in their
      distribution were found. The results show that the amount and distribution of SYN
      IR is temporally related to the maturation and functional activity of human
      sympathetic ganglia neurons. It was suggested that numerous SIF cells and
      paraganglia in human prenatal sympathetic ganglia were both indicative of
      incomplete cell migration and an important source of regulation of ganglionic
      microcirculation under the conditions of relative hypoxia and immature nervous
      regulation.

PMID- 11508361
TI  - Expression of adhesion molecules and fibronectin of activated peritoneal surface
      with lipopolysaccharide (LPS) analyzed with immuno SEM.
AB  - To disclose cell-to-cell interaction associated with the defensive mechanism of
      the peritoneum, the peritoneum was stimulated with lipopolysaccharide (LPS) and
      analyzed three-dimensionally, ultrastructurally, and immunohistochemically with
      immunoSEM (scanning electron microscopy). The activated hepatic peritoneal
      surface demonstrated numerous microvilli with the adhesion molecules ICAM-1 and
      VCAM-1. They were restricted to villi and peaked at 1.5 microg/g body weight of
      LPS. Delicate strands appeared moderately and were interwoven among microvilli
      with increasing LPS. These strands did not express ICAM-1 or VCAM-1, but
      fibronectin. Leukocytes began to adhere to the peritoneal surface above die value
      of LPS (2.5 microg). These results suggest that the peritoneal surface gives a
      defensive sheet for cell-to-cell interaction through adhesion molecules and
      fibronectin.

PMID- 11508362
TI  - An ultrastructural study of osteoclasts and chondroclasts in poorly calcified
      mandible induced by high doses of strontium diet to fetal mice.
AB  - A high dose strontium diet was fed to fetal mice from day 1 of gestation to birth
      in order to investigate the ultrastructural changes of osteoclasts/chondroclasts
      when associated with poorly calcified bone/cartilage. Calcification in the
      mandibular bone and condylar cartilage was extensively inhibited by this diet.
      Multinucleated osteoclasts and chondroclasts were observed on the mandibular
      alveolar bone and in the resorption area of the condylar cartilage, respectively.
      However, both cell types never formed ruffled borders and clear zones at the cell
      surfaces facing the matrices indicative of bone resorption, although they had
      well-developed organelles and vacuoles. Furthermore, they revealed signs of
      phagocytosis of the matrix vesicles. These results indicate that
      osteoclasts/chondroclasts can exhibit phagocytotic activity in response to
      requirements.

PMID- 11508363
TI  - Morphometric analysis of early regeneration of motor axons through motor and
      cutaneous nerve grafts.
AB  - Peripheral nerve damage is a frequent consequence of trauma, tumor surgery or
      diseases. Clinical results of functional reinnervation after the application of
      cutaneous grafts are still unsatisfactory. Differences in the extracellular
      matrix are considered to be one of the factors responsible for poor results of
      motor axon reinnervation through the cutaneous graft. To verify these
      differences, we compared morphological features of the motor axons regenerating
      through the graft prepared from the saphenous nerve and the motor branch of the
      femoral nerve. Eighteen female adult rats (Wistar) were used in experiments. The
      saphenous nerve, the femoral nerve, and its main motor branch were exposed under
      deep anesthesia with ketamine and xylazine. The nerve graft (10 mm) prepared from
      the saphenous nerve was applied between the stumps of the transected motor branch
      of the femoral nerve in the 6 rats. In the next 6 rats, the nerve graft (10 mm)
      harvested from the motor branch of the femoral nerve was inserted between stumps
      of the transected motor branch of the femoral nerve on the contralateral side.
      All rats were perfused with Zamboni's fixative solution 14 days after grafting.
      The samples of grafts and the intact motor branch (n = 6) were dissected and
      embedded in Durcupan ACM. Semithin sections stained with Toluidine Blue were used
      for morphometric analysis of myelinated axons by means of computer-assisted image
      analysis system. Ultrathin sections counterstained with uranyl acetate were
      viewed and photographed in an electron microscope. The number of myelinated motor
      axons showing early regeneration under conditions of the cutaneous and motor
      nerve grafts was similar. The diameter of axons and thickness of their myelin
      sheaths were significantly smaller when the axons regenerated into the saphenous
      nerve in contrast to the motor graft. Morphometric analysis of early regeneration
      of myelinated motor axons suggests that the cutaneous and motor branches of the
      femoral nerve provide different conditions not for the growth but for the
      maturation of motor axons.

PMID- 11508364
TI  - Muscle differentiation after sciatic nerve transection and reinnervation in adult
      rats.
AB  - Reinnervation after peripheral nerve transections generally leads to poor
      functional recovery. In order to study whether changes in muscles might be a
      contributing factor in this phenomenon we studied muscle morphology and fibre
      type distributions after sciatic nerve transection in the rat hind limb.
      Proximally, before the bifurcation in the tibial and common peroneal nerve, a 12
      mm segment of the sciatic nerve was resected, reversed and re-implanted as an
      autologous nerve graft. After survival periods of 7, 15 and 21 weeks the lateral
      gastrocnemius, tibialis anterior and soleus muscles were dissected, stained with
      mATP-ase, and fibre type distributions were studied. In addition, numbers of
      muscle fibres were counted, and cross sectional areas were calculated. After 7
      weeks, cross sectional areas were decreased in all muscles. In the gastrocnemius
      and tibialis anterior muscles the fibre number remained unaltered but the
      hypotrophy had been reversed at later ages. The number of muscle fibres in the
      soleus muscle remained decreased over the entire period of observation. The
      percentages of type II fibres in the gastrocnemius and tibialis anterior muscles
      were decreased at 7 and 15 weeks but these again approached normal values at 21
      weeks. The type I fibres, however, remained arranged in groups. In the soleus
      muscle a large increase in the percentage of type II muscle fibres was observed
      and this remained until 21 weeks. We conclude that a non-selective reinnervation
      and later readjustments by regression of polyneural innervation may in part
      explain the changes in distributions of various fibre types.

PMID- 11508365
TI  - Analysis of the vascular anatomy of the palm and its clinical relevance in Morbus
      Dupuytren.
AB  - The triangular center of the palm is supposedly hypovascularized. Intraoperative
      clinical studies have shown numerous vessels and nerves rising through the palmar
      aponeurosis into the skin in this area. To investigate these findings we have
      dissected 7 cadaver hands in order to analyze the vascular and neural structure
      of the palm. On an average we have found 30 bundles in the center of the palm. At
      least half of them were vascular-nerve bundles, the other bundles consisted
      either of a nerve, an artery or a vein. By means of histological testing we have
      also found lymphatic vessels accompanying the blood vessels and the nerves. Our
      study shows a greater number of vessels rising into the skin than has been
      previously described in the literature, so that we cannot confirm the triangular
      hypovascular zone in the center of the palm.

PMID- 11508366
TI  - Cartilage in pulmonary valves of Syrian hamsters.
AB  - The presence of cartilage in the pulmonary valve has been reported in birds, but
      not in mammals. We describe here the occurrence of cartilaginous tissue in the
      pulmonary valves of 40 (11.4%) of 351 Syrian hamsters examined using
      histological, histochemical and/or immunohistochemical techniques. The
      cartilaginous deposits were located along the fibrous attachments of the valve
      leaflets to the wall of the pulmonary artery trunk. Our findings indicate that
      the proximal attachments of the leaflets to their respective sinuses, and
      especially that of the ventral leaflet, are the most prone valvular regions to
      develop cartilaginous foci. Nonetheless, the possible function of these foci
      remains an open question. Formation of cartilage in the pulmonary valve starts
      within the first month of life, that is during the period in which the valve
      reaches histological maturation. The earliest evidence of chondrogenesis is the
      presence of small groups of cells embedded in a type II collagen-positive
      extracellular matrix. These groups of cells, which can appear as early as one day
      after birth, increase moderately in size and differentiate into hyaline
      cartilaginous tissue. The precursors of the cartilaginous cells are presumed to
      be neural crest-derived elements. However, the factor or factors involved in the
      differentiation of these precursors into chondrocytes are still unknown. In this
      regard, our observations cast doubt on the hypothesis that the formation of
      cardiac cartilages is primarily due to locally intense mechanical stimulation.

PMID- 11508367
TI  - Differentiation and morphogenesis of cerebellar interneurons developing under
      controlled in vitro conditions.

PMID- 11508368
TI  - Polycystic kidney disease--a tale of calcium channels and the actin cytoskeleton.

PMID- 11508369
TI  - Controversial discussions.

PMID- 11508370
TI  - Introduction to "The analyst's participation: a new look" by Jay Greenberg.

PMID- 11508371
TI  - The analyst's participation: a new look.
AB  - Over the past fifteen years or so, advocates of a relational theory of
      psychoanalytic process have developed a compelling challenge to the classical
      approach to clinical work. Their critique of a fixed "standard technique,"
      applicable across the board to all analyzable patients, has been particularly
      effective. The new approach opens the possibility of tailoring technique to
      individual analysands, negotiating the best way of working within each unique
      analytic dyad. But despite the openness of relational theory, many of the most
      influential clinical vignettes in the recent literature emphasize the analyst's
      risk-taking, engaging patients in a highly personal way that breaks the
      traditional analytic frame. Various implications of the tendency of relational
      analysts to emphasize this sort of intervention are discussed, and questions
      raised about the way this may affect how relational thinking is received.

PMID- 11508372
TI  - The interpersonal and Freudian traditions: convergences and divergences.
AB  - The traditional Freudian and interpersonal schools of psychoanalysis diverged
      during the psychoanalytic wars in New York in the 1940s. Each has developed from
      a different set of assumptions concerning the mind, especially the role of
      structure and the role of interaction. Recent developments in both schools in the
      last twenty years suggest a convergence and overlap in theory and technique. The
      relevant history of the divergence is examined and the work of three contemporary
      interpersonal writers explored in depth. That work is contrasted with
      contemporary developments in traditional Freudian psychoanalysis.

PMID- 11508373
TI  - The analyst's knowledge and authority: a critique of the "new view" in
      psychoanalysis.
AB  - A critical assessment is presented of positions recently taken by Mitchell and
      Renik, who are taken as representatives of a "new view" in psychoanalysis. One
      article by Mitchell and two by Renik are examined as paradigmatic of certain ways
      of construing the nature of mind, the analyst's knowledge and authority, and the
      analytic process that are unduly influenced by the postmodern turn in
      psychoanalysis. Although "new view" theorists have made valid criticisms of
      traditional psychoanalytic theory and practice, they wind up taking untenable
      positions. Specifically called into question are their views on the relation
      between language and interpretation, on the one hand, and the mental contents of
      the patient on the other. A disjunction is noted between their discussion of
      clinical material and their conceptual stance, and their idiosyncratic
      redefinitions of truth and objectivity are criticized. Finally, a "humble
      realism" is suggested as the most appropriate philosophical position for
      psychoanalysts to adopt.

PMID- 11508374
TI  - Questioning the psychoanalyst's authority.
AB  - Sources of the trend to question not just the analyst's authority to interpret,
      but the analyst's use of authority in general, are explored. Out of a wish to
      circumvent the potentially detrimental effects an analyst's interpretations can
      have on patients, certain psychoanalysts have modified their analytic techniques
      with an eye to downplaying the role of their authority. When taken to extremes,
      this has led analysts to act as if they have little to offer patients in the way
      of an alternative point of view, and to privilege patients' accounts and
      interpretations by treating them as if they were objectively true. It is argued
      that one need not go so far in order to protect patients from the analyst's less
      than careful use of authority. It is argued further that the judicious use of
      authority remains an indispensable tool in helping to ready the patient's mind
      for a consideration of constructs different from those on which the patient has
      always relied. Finally, becoming comfortable with the aggressive aspect of the
      use of one's authority may determine the extent to which one is willing to employ
      one's authority with patients.

PMID- 11508375
TI  - Critical realism: distinguishing the psychological subjectivity of the analyst
      from epistemological subjectivism.
AB  - To clarify the concepts of critical realism, subjectivity, and subjectivism,
      distinctions are drawn among ontological subjectivism, moral subjectivity,
      psychological subjectivity, and epistemological subjectivism. Psychological
      subjectivity, including the ongoing affective life of the analyst, is an
      essential aspect of the analyst's response to the patient, and may either
      facilitate or distort an adequate observation of transference and
      countertransference dynamics and of the psychic reality of the patient.
      Subjectivism in current psychoanalytic literature involves an argument that there
      is an "irreducible" subjectivity in the analyst, who is bound to see things from
      an incorrigibly personal point of view, such that there is no substantial subject
      object differentiation between analyst and patient. Issues of authoritarianism in
      the analyst, or of pathological certainty, should not be confused with the issues
      of epistemological objectivism. The concept of critical realism or scientific
      objectivism includes the essential idea that there is no pure knowledge, no
      complete knowledge, that often evidence is insufficient for knowledge of some
      aspect of nature, and that care must be to taken understand what is sufficient
      knowledge in a given area, in this case clinical psychoanalysis. The question is
      raised whether "projective identification" makes the sorting out of "what comes
      from whom" impossible. It is argued that when free association is sufficiently
      facilitated, when there are enough corrections of the distortions wrought by
      transference and countertransference, when defenses are analyzed, and when
      sufficient subject-object differentiation is recovered, the analyst can get to
      know enough of the patient's psychic reality for the therapeutic and scientific
      purposes of psychoanalysis.

PMID- 11508376
TI  - Metaphors of a bodily mind.
AB  - Patients' metaphors in analysis may allow access to ineffable experiences. This
      is understandable, since the mind is a bodily mind, and language is a fully
      embodied function of this mind. That is, both are dependent for their existence
      upon the physical body. The ontogenic accumulation of perceived sensory
      impressions and affective processes far exceeds what can be put into words.
      Research in cognitive psychology suggests that the active mind functions in such
      a manner that later perceptions are organized by means of earlier ones. However,
      since the mind can know only its own representations, it inhabits two ever
      unknown realms: the external world itself, and the domain of internal unconscious
      processes that sustain the mind's functions. As a result, the world and the self
      we know are constructed by the mediation of our bodies. In language also, the
      active mode by which we perceive, process, and feel makes our understanding of
      words dependent on previous experience. The fact that the limbic system is
      activated immediately in the moment of processing experience means that all
      modalities of representation include an affective valuation. This inevitable
      processing of information through the mediation of affectively valued bodily
      perceptions gives the metaphorical function-the human capacity to organize
      experience and life in metaphoric ways-the ability to create linguistic metaphors
      that can capture and express otherwise inexpressible psychic experiences. This
      manner of understanding metaphor has implications for psychoanalytic technique.

PMID- 11508377
TI  - Life-threatening illness in the analyst.
AB  - The literature on practicing throughout a life-threatening illness is reviewed
      and important differences about attitudes toward self-disclosure are understood
      by noting a division between two perspectives on transference: "one-body" and
      "two-body" views. The analyst's use of self-disclosure is informed by the
      prominence given the interpretation of transference as against that given the
      patient's needs in the collaborative relatedness supporting the therapeutic
      alliance. Themes and illustrative clinical vignettes are presented from the
      author's own experience practicing during such an illness. Three phases of
      working during illness are delineated, each somewhat different regarding the
      analyst's state, and hence patients' needs and reactions. Recommendations are
      made regarding conditions that make it possible to work effectively during a life
      threatening illness. The analyst needs help from his or her own analyst to make
      the clinically and sometimes ethically appropriate decisions about practice;
      while this is important in instances in which the analyst recovers, it is
      essential should the analyst become terminal and face more certain death.

PMID- 11508378
TI  - Concurrent therapies: a model for collaboration between psychoanalysts and other
      therapists.
AB  - Many psychoanalysts treat individuals who are simultaneously in couples therapy
      or whose partners are in individual therapy. If such cases stall, some analysts
      may seek consultation from a colleague, though most have accepted the tacit
      historical prohibition against communication between therapists treating members
      of the same family. Experience, however, suggests that a certain form of
      communication between such therapists can have a powerfully enhancing effect on
      the concurrent therapies. After a review of the literature, the advantages,
      disadvantages, and impediments to collaborative cross-communication are examined.
      A model is then presented for use in ongoing discussion between therapists, and
      is illustrated with two clinical examples. The proposed model centers on the
      transference-countertransference configurations within the therapeutic field, and
      serves as an organizer highlighting areas for discussion.

PMID- 11508379
TI  - The effects of the introduction of medication on the psychoanalytic process: a
      case study.
AB  - The past fifteen years have seen a marked change in the attitude of
      psychoanalysts toward the use of medication in psychoanalysis, yet few detailed
      case studies have appeared in which the effects of the introduction of a
      medication on the psychoanalytic process have been studied. A plea for fluoxetine
      (Prozac) as a weight-loss aid, from a female patient whose analysis had
      progressed satisfactorily, set in motion a remarkable series of events. Her mood
      brightened, she rapidly lost weight, and she ultimately realized that she had the
      fantasy of being impregnated, all of which represented the reenactment of crucial
      childhood experiences. The most significant change in the psychoanalytic process
      was a newfound ability to experience critical thoughts and feelings, which
      previously had been prohibited by her harsh superego. At first both patient and
      analyst believed that the medication had "softened" her superego, but
      reexamination of the data revealed that most, if not all, of the changes could be
      attributed to the transference meaning of the collaboration rather than to the
      effects of the drug.

PMID- 11508380
TI  - On "Telepathic dreams?": an unpublished paper by Robert J. Stoller.
AB  - In 1973 Robert Stoller wrote a paper on a series of dreams-his own and his
      patients'--that he reluctantly found himself calling "telepathic." He never
      submitted the paper for publication, though he returned to the topic of
      unconscious communication and telepathy with increasing fascination in the years
      before his death. Publication of Stoller's paper seems particularly opportune
      just now. In it he pleads for open-minded examination of data, however alien to
      current scientific belief those data seem. In the past, despite numerous
      published reports of possibly telepathic experiences in analysis, their
      investigation remained relatively one-sided, since a technical posture of
      anonymity with patients constrained analysts from revealing that a communication
      struck them as telepathic. This has limited what analysts have been able to learn
      about the information actually exchanged, how it was exchanged, and whether the
      communication was experienced as uncanny by the patient. Recent attention to the
      intersubjective nature of the analytic situation has led to a deemphasis of
      anonymity, opening freer dialogue that may facilitate the rigorous investigation
      Stoller calls for. Such investigation may further analytic understanding of
      unconscious mental function and communication in the clinical setting, and lend
      perspective to the growing body of carefully controlled experimental research on
      anomalous mental phenomena.

PMID- 11508381
TI  - Speaking the unspeakable: institutional reactions to boundary violations by
      training analysts.
AB  - The work of a COPE study group on boundary violations is summarized, with
      particular focus on the impact on institutes and societies of sexual misconduct
      by training analysts. Difficulties in evaluating such situations are discussed,
      and the dynamics of institutional avoidance explicated. In addition,
      psychodynamic themes that are commonly observed in analysts who engage in sexual
      boundary violations with their patients are elaborated. Finally, suggestions are
      made for managing, through existing mechanisms, instances of boundary violations
      by training analysts.

PMID- 11508382
TI  - Longitudinal study of natural immune responses to the Plasmodium falciparum
      apical membrane antigen (AMA-1) in a holoendemic region of malaria in western
      Kenya: Asembo Bay Cohort Project VIII.
AB  - We investigated the development and maintenance of proliferative and antibody
      responses to apical membrane antigen-1 (AMA-1) epitopes in a holoendemic area of
      western Kenya. Young children (< 10 years), older children (10-17 years), and
      adults (> or = 18 years) were followed longitudinally for antibody and T-cell
      responses at 3 time points with an interval of 3-4 months. The proliferative
      responses against the AMA-1 T epitopes (PL171, PL172, PL173, PL186, PL191, and
      PL192) were not stable during follow-up; however, response to mycobacterial
      antigen PPD was highly stable. The responder frequencies were similar in all 3
      time points except for epitope PL192. The younger and older children responded
      more frequently to T-cell epitopes, but the differences were not significant. A
      positive proliferative response to PL191 was associated with a significantly
      lower risk of parasitemia at subsequent follow-up (relative risk, 0.5; P = 0.03).
      The presence of antibody response to B epitopes PL169, PL170, PL173, PL187, and
      PL192 in one time point was associated with a subsequent response (P = 0.0001
      0.008) suggesting a stable response. Younger (P = 0.046) and older children (P =
      0.017) more frequently responded to epitope PL169 than did adults, and adults
      responded more frequently to PL187 than did younger children (P = 0.009).
      Responses to AMA-1 T-cell epitopes were short lived, and antibody responses were
      relatively stable.

PMID- 11508383
TI  - The Carter Center's assistance to river blindness control programs: establishing
      treatment objectives and goals for monitoring ivermectin delivery systems on two
      continents.
AB  - Periodic mass treatment with ivermectin in endemic communities prevents eye and
      dermal disease due to onchocerciasis. As part of an international global
      partnership to control onchocerciasis, The Carter Center's Global 2000 River
      Blindness Program (GRBP) assists the ministries of health in ten countries to
      distribute ivermectin (Mectizan, donated by Merck & Co.). The GRBP priorities are
      to maximize ivermectin treatment coverage and related health education and
      training efforts, and to monitor progress through regular reporting of ivermectin
      treatments measured against annual treatment objectives and ultimate treatment
      goals (e.g., full coverage, which is defined as reaching all persons residing in
      at risk villages who are eligible for treatment). Since the GRBP began in 1996,
      more than 21.2 million ivermectin treatment encounters have been reported by
      assisted programs. In 1999, more than 6.6 million eligible persons at risk for
      onchocerciasis received treatment, which represented 96% of the 1999 annual
      treatment objective of 6.9 million, and 78% of the ultimate treatment goal in
      assisted areas.

PMID- 11508384
TI  - Antioxidant status and acute malaria in children in Kampala, Uganda.
AB  - Although antioxidant status has been implicated in the pathogenesis of malaria,
      these factors need further characterization. A longitudinal study was conducted
      involving 273 children 1-10 years of age with acute, uncomplicated malaria in
      Kampala, Uganda. Plasma vitamin A, carotenoids, and vitamin E were measured at
      enrollment and on day 7. Malaria parasitemia was measured at enrollment, on day
      3, and on day 7. Malaria parasitemia had completely cleared in 57.1% and 85.3% of
      children by day 3 and day 7, respectively. Plasma vitamin A, alpha-carotene, beta
      carotene, lycopene, lutein/zeaxanthin, and vitamin E were depressed at enrollment
      and increased by day 7. Multivariate analyses showed that higher plasma lycopene
      concentrations at enrollment were associated with clearance of parasitemia
      between enrollment and day 3 (odds ratio = 1.46, 95% confidence interval = 1.07
      2.06, per 0.10 micromol/L of lycopene). This study suggests that children with
      acute malaria have depressed plasma concentrations of antioxidants, and that
      higher plasma lycopene is associated with more rapid clearance of malaria
      parasitemia.

PMID- 11508385
TI  - Toxins and colonization factor antigens of enterotoxigenic Escherichia coli among
      residents of Jakarta, Indonesia.
AB  - Infection caused by enterotoxigenic Escherichia coli (ETEC) poses a serious
      health problem among children and adults in developing countries. Colonization of
      the small intestinal mucosa by ETEC strains is mediated by antigenically specific
      fimbriae, also known as colonization factor antigens (CFA). The significance of
      this study arises from reports that active and passive immunization with ETEC
      strains harboring CFAs has previously been shown to induce protective immunity
      against diarrhea in animal models. The aim of this study was to determine toxin
      associated CFAs of ETEC isolated from a diarrheal disease case-control study in
      Jakarta, Indonesia. Thirteen hundred and twenty-three diarrheic and control
      patients with lactose-fermenting colonies were screened by ganglioside GM1-enzyme
      linked immunosorbent assay (GM1-ELISA) for heat-labile (LT) and heat-stable (ST)
      toxins. Two hundred and forty-six (19%) ETEC isolates identified by GM1-ELISA for
      the LT/ST toxins were screened for CFAs by Dot blot assay using monoclonal
      antibodies against CFA/I, II, and IV and against the putative colonization
      antigens (PCF) PCFO159, PCFO166, CS7, and CS17. Of the 246 ETEC isolates, 177
      (72%) elaborated ST, 56 (23%) produced LT, while 13 (5%) elicited both the ST and
      LT toxins. CFA testing of the 246 ETEC isolates showed that 21 (8%) expressed
      CFA/I, 3 (1%) exhibited CFA/II, 14 (6%) elaborated CFA/IV, while 7 (3%) expressed
      PCFO159 and PCFO159 plus CS5. No CFAs or PCFs could be associated with 201 (82%)
      of the ETEC strains. This report documents the types of CFAs associated with ETEC
      strains in Jakarta, Indonesia. These data may help current research efforts on
      the development of CFA-based vaccines for humans against ETEC and provide
      additional information for future ETEC vaccine trials in Southeast Asia.

PMID- 11508386
TI  - Probability of Trypanosoma cruzi transmission by Triatoma infestans (Hemiptera:
      Reduviidae) to the opossum Didelphis albiventris (Marsupialia: Didelphidae).
AB  - The probability of Trypanosoma cruzi transmission to opossums by independent
      events of predation and fecal contamination during feeding ("biting") with
      positive Triatoma infestans was estimated. Negative female opossums were
      challenged for 23 hr with 10 infected third and fourth instars of T. infestans,
      and tests for positivity for T. cruzi by xenodiagnosis were performed at 30, 60,
      and 90 days. From these data, seven probability parameters were estimated by
      maximum likelihood, and likelihood ratio statistics confidence intervals were
      calculated. Simultaneous estimation of p1 (probability that a "bite" will infect
      an opossum), p3 (probability that a bug that has been eaten by an opossum will
      infect it), and p6 (probability that the opossum will become infected if faced
      with an infected triatomine), resulted in p1 = 0.06, p3 = 0.075, and p6 = 0.059.
      On average, each opossum should be exposed to an average of 700 encounters with
      bugs during its life, resulting in about eight potentially infective contacts, to
      produce the 35% opossum prevalence found in the field.

PMID- 11508387
TI  - Seroepidemiology of toxoplasmosis in amerindians from western Venezuela.
AB  - A survey of 447 Amerindians aged 1-69 years (mean age, 18.6 +/- 15.8 years) in 3
      mountain and 1 lowland communities from Venezuela were studied to determine the
      seroprevalence of Toxoplasma gondii, the environmental risk factors for the
      infection, and how the process of acculturation may affect the transmission rate.
      Serum samples were tested for immunoglobulin G antibodies by a commercial
      indirect hemagglutination test. The overall prevalence of infection was 49.7%
      (222 of 447) and ranged 38.2-62.4%. A higher antibody rate was found in the
      lowland setting as compared with those from the mountain area (P < 0.001). The
      geometric mean titer in the overall population was 280.3. No age-antibody
      association was detected in the mountain communities, although a gradual increase
      in positivity with increasing age (P < 0.01) was observed in the lowland setting,
      reaching a peak of 83.3% in the oldest group. The results suggest that
      transmission by infective cat feces may play a predominant role in the spread of
      infection in this population. This study demonstrates the environmental
      Toxoplasma infection pressure in this sylvatic population and how transmission
      rate is facilitated by environmental changes produced by acculturation.

PMID- 11508388
TI  - Short report: Hookworm infection is associated with decreased body temperature
      during mild Plasmodium falciparum malaria.
AB  - Malaria's pyrogenic threshold seems to depend on factors such as age and
      transmission patterns. We studied the temperature at admission of 200 patients
      with mild malaria and observed that after adjusting for body mass index, the
      presence of other helminths, and other confounders, only hookworm-infected
      patients had lower fever at admission that those without hookworm infection (37.5
      +/- 0.9 and 38 +/- 0.8, respectively; P < 0.001). Thus, we suggest the age
      dependence of the pyrogenic threshold could have been confounded by the
      epidemiology of iron deficiency.

PMID- 11508389
TI  - Effect of malaria on soluble transferrin receptor levels in Tanzanian infants.
AB  - The diagnosis of iron deficiency anemia in malaria endemic areas is complicated
      by the influence of the infection on the laboratory tests conventionally used to
      assess iron status. Determination of soluble transferrin receptor (sTfR) levels
      has been shown to be a sensitive indicator of iron deficiency in adults and is
      not affected by a range of infectious and inflammatory conditions. The utility of
      sTfR levels in the diagnosis of iron deficiency in malaria endemic areas remains
      unresolved. Three hundred and fourteen infants in a rural area of southern
      Tanzania living under conditions of intense and perennial malaria transmission
      were studied to determine the utility of sTfR plasma levels in the assessment of
      iron deficiency anemia. Independent of the presence of anemia, malaria
      parasitemia was associated with a significant increase in sTfR plasma levels that
      were even higher than those found in iron deficiency anemia. We conclude that the
      measurement of sTfR levels does not have a role in the diagnosis of iron
      deficiency anemia in young children exposed to malaria infection.

PMID- 11508390
TI  - Clinical features of vivax malaria.
AB  - Plasmodium vivax malaria reemerged in the Republic of Korea in 1993 near the
      Demilitarized Zone (DMZ). We reviewed clinical features of 101 symptomatic
      patients with vivax malaria. Of the patients, 77 patients (76.3%) were veterans
      who had served near the DMZ; their median age was 23 years. The duration of the
      minimum latent period was > 6 months in 66.2% (51 of 77) of the patients (median,
      278 days). Tertian fever developed in 69 patients (68.3%). Severe
      thrombocytopenia with platelet counts < 60,000/microL was common (29.6% of
      patients). The parasite densities ranged 32-52,127 parasites per microliter of
      blood (geometric mean, 1,287). The only complication was a splenic rupture in one
      patient. All patients responded promptly to chloroquine therapy. Our data suggest
      that the clinical features of reemerging vivax malaria may be similar to those of
      Korean vivax malaria reported in the past.

PMID- 11508391
TI  - Experimental infection of Neotoma albigula (Muridae) with Whitewater Arroyo virus
      (Arenaviridae).
AB  - The Whitewater Arroyo virus (WWA) is a newly described North American arenavirus.
      The purpose of this study was to elucidate the biology of this virus in its
      natural rodent host, Neotoma albigula (white-throated woodrat). Thirteen adult, 7
      juvenile, and 8 newborn woodrats each were inoculated subcutaneously with 1,000
      cell culture infectious dose50 of the WWA virus prototype strain AV 9310135. All
      28 animals became infected (as measured by the recovery of infectious virus
      and/or seroconversion) and no overt illness was associated with infection.
      Infection and virus shedding in the adult animals were transient (less than 59
      days) whereas virus shedding in animals inoculated at birth persisted through 164
      days of age. These results indicate that the duration of WWA virus infection in
      N. albigula is dependent upon the animal's age at the onset of infection and that
      neonatal infection can result in chronic (perhaps lifelong) virus shedding.

PMID- 11508392
TI  - Mouse model for Chagas disease: immunohistochemical distribution of different
      stages of Trypanosoma cruzi in tissues throughout infection.
AB  - Different stages of Trypanosoma cruzi are seen during mammalian infection.
      Histologic sections of infected hearts have shown amastigotes and, when using
      immunohistochemistry (IHC), parasite antigens; however, demonstration of
      trypomastigotes in these tissues has proven elusive. Using a mouse strain that
      develops chagasic cardiomyopathy (histologically similar to human infection) 70
      days after injecting T. cruzi-Brazil strain, we studied the distribution of
      parasite stages and the extent of inflammation. All organs had varying amounts of
      mononuclear inflammation by day 10, which peaked between day 20 and day 30, and
      decreased by day 50. Amastigotes were detected in myocytes, histiocytes, acinar
      pancreatic cells, astrocytes and ependymal cells by day 10, and the number of
      amastigotes peaked on day 30. Immunohistochemistry demonstrated trypomastigotes
      in sinusoids, vessels and interstitial tissues of several organs between day 15
      and 50. Abundant parasite antigens (granular staining) were detected in
      connective tissues throughout the infection. The burden of amastigotes and
      trypomastigotes during the acute phase seems to correlate with the degree of
      inflammation and granular staining in the chronic stage.

PMID- 11508393
TI  - Short report: Antibody responses of mice immunized with a tetravalent dengue
      recombinant protein subunit vaccine.
AB  - Recombinant proteins containing the B domain of dengue virus serotypes 1-4 fused
      to the maltose binding protein (MBP) of Escherichia coli were evaluated
      individually and as a tetravalent vaccine candidate in mice. Sera from mice
      immunized with monovalent DEN-MBP recombinant protein vaccines developed high
      titers of serotype homologous antibody in the enzyme-linked immunosorbent assay
      and the plaque-reduction neutralization test. Cross-reactive antibody titers were
      either several dilutions lower or not detectable. Sera from mice immunized with
      the tetravalent DEN subunit vaccine neutralized all 4 DEN viruses in the plaque
      reduction neutralization test. The neutralizing antibody titers to each
      individual serotype were significantly greater than any cross-reactive
      neutralizing antibody titers induced by the monovalent vaccines, providing
      evidence that the tetravalent DEN recombinant subunit vaccine produced specific
      neutralizing antibody to all 4 serotypes of dengue virus.

PMID- 11508394
TI  - Short report: A practical technique for the cryopreservation of Dirofilaria
      immitis, Brugia malayi, and Wuchereria bancrofti microfilariae.
AB  - A technique to cryopreserve microfilariae has been developed. This method was
      used to cryopreserve microfilariae of Dirofilaria immitis, Brugia malayi, and
      Wuchereria bancrofti at a controlled rate of 1 degree C/min by use of a freezing
      tank. Microfilariae of each of these species retained their ability to infect
      susceptible mosquito species and develop to the infective stage after
      cryopreservation. The method presented here is quickly and easily carried out
      with inexpensive equipment.

PMID- 11508395
TI  - Short report: Detection of borrelia (relapsing fever) in rural Ethiopia by means
      of the quantitative buffy coat technique.
AB  - The diagnosis of louse-borne relapsing fever is commonly made on the basis of the
      detection of Borrelia spirochetes on Giemsa-stained thin blood films. In the
      present study, we used acridine orange-coated quantitative buffy coat (QBC)
      tubes, centrifugation, and fluorescence microscopy to detect Borrelia. Between
      July and August 1998, we used the QBC technique to diagnose 7 patients with
      borreliosis who visited a rural clinic in southwest Ethiopia. In laboratory
      studies that used Borrelia burgdorferi as a model, we detected spirochetes at
      concentrations as low as 10 organisms/mm3, whereas the number of positive
      readings assessed by means of stained blood films fell significantly at dilutions
      below 3,263 organisms/mm3. The greater sensitivity of the QBC technique is
      important in areas where Borrelia is endemic, as in the Horn of Africa. It may
      also prove useful in evaluating relapsing fevers in travelers.

PMID- 11508396
TI  - Successful treatment of refractory mucosal leishmaniasis with pentoxifylline plus
      antimony.
AB  - Mucosal leishmaniasis is characterized by an intense inflammatory reaction and
      tissue damage with few parasites in the lesion. On the basis of previous
      observations that suggest a possible role of tumor necrosis factor alpha (TNF
      alpha) in the pathology of this disease, an open-label study was performed to
      evaluate the efficacy of the treatment with an inhibitor of TNF-alpha
      (pentoxifylline) associated to antimony therapy in 10 patients with refractory
      mucosal leishmaniasis. Patients were treated with pentavalent antimony (20 mg per
      kilogram of body weight per day) plus orally administered pentoxifylline 400 mg 3
      times daily for 30 days. Nine of 10 patients fulfilled the criteria for cure:
      they experienced complete reepithelization of the mucosal tissue 90 days after
      therapy and displayed no evidence of relapse at 1 year of follow-up. The TNF
      alpha levels before therapy (776 +/- 342 pg/mL) fell to 94 +/- 57 pg/mL (P <
      0.05) within 60 days after therapy. Our results indicate that pentoxifylline plus
      antimony therapy should be considered in all patients with mucosal leishmaniasis
      that is refractory to treatment.

PMID- 11508397
TI  - Plasmodium vivax clinically resistant to chloroquine in Colombia.
AB  - Chloroquine-resistant Plasmodium vivax has been the subject of numerous case
      reports and prospective studies from Oceania and Asia. In contrast, only case
      reports exist from the Americas. We performed a prospective study with 28-day
      follow-up of clinical responses to chloroquine in 2 P. vivax-endemic regions of
      Colombia. Three (11%) of 27 patients failed to respond to treatment with the
      standard regimen of chloroquine (1,500 mg of base over 3 days). One patient
      demonstrated RI resistance on Day 26; one patient demonstrated RI resistance due
      to recrudescence of blood stages on Day 11; and one patient demonstrated RII
      resistance of blood stages by never displaying clearing of peripheral
      parasitemia. All patients were successfully treated with primaquine, which has
      some blood stage efficacy against P. vivax, combined with a second course of
      chloroquine. Clinical resistance of P. vivax to chloroquine is present in
      Colombia and should be monitored in the Americas.

PMID- 11508398
TI  - Case report: Nitazoxanide treatment failure in chronic isosporiasis.
AB  - We report a 60-year-old immunocompetent patient with chronic biliary isosporiasis
      who failed to respond to orally administered cotrimoxazole prophylaxis and orally
      administered treatment with nitazoxanide, a 5-nitrothiazole benzamide compound.
      Severe malabsorption was regarded as responsible for the subtherapeutic levels of
      nitazoxanide in plasma and bile, resulting in treatment failure. Intravenously
      administered cotrimoxazole stopped the shedding of Isospora belli oocysts in bile
      within 5 days, excluding initially suspected resistance to cotrimoxazole.
      Patients with malabsorption and cholangitis due to Coccidia such as Isospora
      belli and Cryptosporidium spp. or due to protozoa that cause microsporidiasis
      seem to be predisposed to fail to respond to otherwise effective treatment.

PMID- 11508399
TI  - Preliminary study of therapeutic efficacy of a new fasciolicidal drug derived
      from Commiphora molmol (myrrh).
AB  - Myrrh (from the stem of the Commiphora molmol tree) is an oleo gum resin that may
      prove efficacious for the treatment of fascioliasis. We studied 7 patients who
      were passing Fasciola eggs in their stools and treated them with myrrh. The drug
      (a formulation consisting of 8 parts of resin and 3.5 parts of volatile oils, all
      extracted from myrrh) was given in a dose of 12 mg/kg per day for 6 consecutive
      days in the morning on an empty stomach. Patients were followed for 3 months. The
      therapy proved to be effective, with pronounced improvement of the general
      condition and amelioration of all symptoms and signs. A dramatic drop in the egg
      count was detected at the end of treatment. Eggs were no longer detectable in the
      feces 3 weeks after treatment and after a follow-up period of 3 months. High
      eosinophilic counts, elevated liver enzymes, and Fasciola antibody titers
      returned to nearly normal. No signs of toxicity or adverse effects were observed.
      We conclude that the formulation of myrrh is safe, well tolerated, and effective
      for treating fascioliasis.

PMID- 11508400
TI  - Wheelchair armrest strength testing.
AB  - There are about 1.4 million manual wheelchair users, 100,000 electric-powered
      wheelchair users, and 60,000 electric-powered scooter users. The current study
      was undertaken to determine if the fasteners of a clamp-type armrest receiver
      were prone to failure. The first test was used to examine the potential
      misalignment of the armrest receiver components that attach it to the frame. The
      second test was to evaluate the entire armrest using the American National
      Standards Institute/Rehabilitation Engineering and Assistive Technology Society
      of North America armrest static strength standard. Finally, we conducted three
      fatigue tests. The first fatigue test was performed by repeating the static
      stability tests multiple times. The last two tests were a modified version of the
      double-drum wheelchair fatigue test used to apply repeated loading and vibration
      simultaneously. A paired t-test showed that there is no statistically significant
      difference (p = 0.08), with a confidence of 95%, between critical alignment
      measurements. The armrest including the receiver passed the standard requirement
      of a force of 760 N being applied outward at 15 degrees. During fatigue testing,
      we found that armrests did not exhibit any visible or functional damage. Upon
      completion of the tests, the armrests and receivers functioned properly. At about
      100,289 cycles on a double-drum test machine, three bolts failed on each armrest
      receiver when the screws were loosened to have only five threads engaged prior to
      commencing the test. The design of the armrest tested was in compliance with
      existing national and international standards. Currently, both International
      Standards Organization and American National Standards Institute/Rehabilitation
      Engineering and Assistive Technology Society committees are developing standards
      for seating systems that will include static, impact, and fatigue strength
      testing of devices like lateral torso supports, lateral hip support, etc. Methods
      similar to those explored in this study should be considered. This study may help
      manufacturers when designing products and purchasers or regulatory agencies when
      attempting to evaluate the safety and quality of armrest assemblies.

PMID- 11508401
TI  - Modifying a motor go-kart to accommodate children with disabilities.
AB  - As an educational exercise with real-world application, a standard motor go-kart
      was altered so that a person with disabilities could control it with one hand via
      a joystick. The first step was to establish the exact design requirements. Then
      the power systems to operate the steering, throttle, and brakes were selected and
      the analog control circuits and amplifiers to drive and control the power systems
      were built. Finally, the mechanisms to connect the power systems to the various
      functions on the go-kart were designed and built. The complete system was then
      tested with a group of children with disabilities, and problems with the system
      were identified.

PMID- 11508402
TI  - Psychosocial impact of electronic aids to daily living.
AB  - Electronic aids to daily living (EADLs) allow persons who have a degenerative
      neuromuscular condition such as Duchenne's muscular dystrophy to operate a wide
      variety of household and workplace appliances without assistance (independent of
      family members or other caregivers). There is very little published research to
      describe how well EADLs are perceived by users to enhance their sense of personal
      autonomy, functional independence, and psychological well being. Psychosocial
      impact is a significant determinant of how users perceive the benefit of
      assistive devices to their quality of life. This study compared the perceived
      psychosocial impact of EADLs on a group of device users with the anticipated
      impact of EADLs reported by a group who were eligible for, but had not yet
      received, these devices. The perceptions of the user group were measured at two
      points in time, approximately 6 to 9 months apart, to examine the stability of
      psychosocial impact. The Psychosocial Impact of Assistive Devices Scale was the
      instrument used to assess perceived impact. EADLs were found to produce similar
      degrees of positive impact on users and positive perceptions of anticipated
      impact on those without devices. The psychosocial impact on users was stable over
      time. The results indicate that the perceived benefits of EADLs to the autonomy,
      functional independence, and psychological well being of both users and nonusers
      are positive and strikingly similar. The study is an important first step in
      attempting to quantify psychosocial outcomes for EADLs in a way that might
      facilitate economic analysis of these devices in the future.

PMID- 11508403
TI  - Classroom evaluation of the Arlyn Arm robotic workstation.
AB  - High school and junior high school students with neuromuscular weakness and other
      disorders of the arms evaluated a recently commercialized robotic workstation,
      the Arlyn Arm, to carry out art projects and science experiments. These tasks
      were designed for independent execution with the workstation using standard or
      custom-designed tools. Each task was divided into subtasks, and the execution
      time of each subtask was determined as a measure of efficiency. Special attention
      was given to the causes of required experimenter intervention. While subjects
      easily accomplished some subtasks, others required considerable intervention.
      Most of these interventions could be avoided by further customizing accessories.
      It is concluded that the Arlyn Arm workstation could be of considerable benefit
      in a classroom setting to persons with severe neuromuscular disorders.

PMID- 11508404
TI  - Science and technology policy: is disability a missing factor?

PMID- 11508405
TI  - The digital divide.

PMID- 11508406
TI  - Item analysis of the Quebec User Evaluation of Satisfaction with Assistive
      Technology (QUEST).
AB  - The Quebec User Evaluation of Satisfaction with Assistive Technology (QUEST) is
      an outcomes assessment tool designed to measure satisfaction with assistive
      technology in a structured and standardized way. The purpose of this article is
      to present the results of an analysis of the 24 items comprising QUEST and to
      explain how a subset of items demonstrating optimal measurement performance was
      selected. The criteria against which the items were measured were general
      acceptability, content validity, contribution to internal consistency, test
      retest stability, and sensitivity. The items that ranked best in terms of these
      measurement properties were submitted to factorial analysis in order to complete
      the item selection. The first series of analyses reduced the item pool
      approximately by half, and the second series of analyses led to the final
      selection of 12 items. Factor analysis results suggested a bidimensional
      structure of satisfaction with assistive technology related to the assistive
      technology device (eight items) and services (four items). The 12-item revised
      version that will result from this study should prove to be a reliable and valid
      instrument for measuring outcomes in the field of assistive technology.

PMID- 11508407
TI  - Whose shoes?

PMID- 11508408
TI  - Back to the floor.

PMID- 11508409
TI  - Panoramic radiography in adult patients.

PMID- 11508411
TI  - Microbial aerosols.

PMID- 11508410
TI  - Panoramic radiography in adult patients.

PMID- 11508412
TI  - Academics for dental primary care.
AB  - Driven by the need to address integrated dental care, many UK dental schools have
      recognised the advantages of teaching dental practice, or dental primary care
      (DPC), as a separate and defined subject area. In such schools, DPC may be taught
      alongside specialist subjects such as restorative dentistry, oral surgery, oral
      medicine and those traditionally forming elements of the dental undergraduate
      curriculum. As a result, departments or units of general dental practice or DPC
      have been established.

PMID- 11508413
TI  - Analysing information.
AB  - The process of gathering information should remain completely separate from the
      process of analysing it, or else assumptions can be made that might lead the
      organisation into some hasty training without appreciating the full picture.

PMID- 11508414
TI  - Chronic idiopathic orofacial pain: II. What can the general dental practitioner
      do?
AB  - Currently, the majority of facial pain patients are referred onto specialists but
      there are treatment options available to the primary care practitioner and,
      indeed, good reasons for interception at the acute stage to prevent the
      development of chronicity. This paper attempts to synthesize contemporary theory
      and clinical evidence into a management strategy for the general dental
      practitioner.

PMID- 11508415
TI  - Displaced polishing discs: two case reports.
AB  - Routine dental treatment is not without its hazards. Two cases of trauma to the
      buccal soft tissues caused by displaced polishing discs are reported and
      suggestions made regarding the long-term use and maintenance of dental
      instruments.

PMID- 11508416
TI  - The use and maintenance of visible light activating units in general practice.
AB  - AIM: The present study to investigate the use, care and maintenance of light
      units in everyday clinical practice was undertaken to complement light unit
      emission surveys, with a view to developing a protocol for light unit use and
      care in everyday clinical practice. METHOD: The investigative work comprised a
      survey of selected practices in the Blackburn area with follow-up practice visits
      to examine light units in situ, and to glean additional information in respect of
      light unit use and care in the practice environment. RESULTS: Completed
      questionnaires were returned by 54 of 77 selected practices--a 70% response,
      including information in relation to 164 light units. Subsequently, 100 (61%) of
      these light units were examined in 42 practices according to a standardised
      protocol. The use and care of the light units included in the study was found to
      be very variable. In addition to finding that 28 (28%) had inadequate light
      output (<300 mW/cm2), many of the light units were found to be damaged or
      repaired (47, 47%). Thirty five (35%) of the light units inspected were found to
      have varying amounts of material adherent to the light guide exit portal.
      CONCLUSION: It is concluded that practitioners should address practical aspects
      of their increasing reliance on light units, and to this end, guidance is offered
      on visible light curing and the care and maintenance of light units.

PMID- 11508417
TI  - Cross infection control measures and the treatment of patients at risk of
      Creutzfeldt Jakob disease in UK general dental practice.
AB  - AIMS: To determine the suitability of key infection control measures currently
      employed in UK dental practice for delivery of dental care to patients at risk of
      prion diseases. MATERIALS AND METHODS:  SUBJECTS: Five hundred dental surgeons
      currently registered with the General Dental Council of the UK. DATA COLLECTION:
      Structured postal questionnaire. ANALYSIS: Frequencies, cross-tabulations and chi
      squared analysis. RESULTS: The valid response rate to the questionnaire was 69%.
      33% of practices had no policy on general disinfection and sterilisation
      procedures. Only 10 of the 327 responding practices (3%) possessed a vacuum
      autoclave. 49% of dentists reported using the BDA medical history form but less
      than 25% asked the specific questions recommended by the BDA to identify patients
      at risk of iatrogenic or familial CJD. However, 63% of practitioners would refer
      such patients, if identified, to a secondary care facility. Of the 107
      practitioners who were prepared to provide dental treatment, 75 (70%) would do so
      using routine infection control procedures. CONCLUSIONS: Most of the dental
      practices surveyed were not actively seeking to identify patients at risk of
      prion diseases. In many cases, recommended procedures for providing safe dental
      care for such patients were not in place.

PMID- 11508418
TI  - Does vocational training encourage continuing professional development?
AB  - The aim of this study was to compare the continuing professional development of
      young dentists who had participated in a vocational training scheme with that of
      young dentists who had not. It was encouraging to find both groups were actively
      involved in a broad range of continuing educational activities.

PMID- 11508419
TI  - Dental transfigurements in Borneo.
AB  - Dental transfigurement, formerly termed dental mutilation, has been practised by
      many societies worldwide. This article gives many of the forms that have been
      attributed to the indigenes of the island of Borneo. The method has been
      performed by review of anthropological books, sparse dental references, Borneo
      research literature, and popular writing.

PMID- 11508420
TI  - Anti-Ro/SSA antibodies and congenital heart block: necessary but not sufficient.

PMID- 11508421
TI  - Response criteria and criteria for clinically important improvement: separate and
      equal?

PMID- 11508422
TI  - The immune tolerance network and rheumatic disease: immune tolerance comes to the
      clinic.
AB  - The development of effective, new, biologically based therapies for RA has
      created real excitement and justifiable optimism in recent years among
      rheumatologists and among patients with rheumatic diseases. Recent advances in
      our understanding of the mechanisms of immune activation and immune tolerance
      provide further cause for optimism. Against this background, the establishment of
      the ITN is an important step. However, significant hurdles remain to be cleared.
      First, despite dramatic scientific progress, restoration of immune tolerance in
      the face of an established autoimmune response is still an elusive goal, even in
      the laboratory. Not only does the ITN face this fundamental scientific challenge,
      but it also faces daunting practical and political challenges. For example, can
      the ITN influence the research agenda of the pharmaceutical and biotechnology
      industries? This question and other important questions will only be answered as
      the ITN matures. Autoimmune disease, although individually uncommon, affects more
      than 2% of Americans. The rheumatologist is especially aware of the devastating
      potential of autoimmune diseases. If the ITN succeeds in linking basic research
      into the mechanisms of autoimmunity with clinical trials of promising new
      therapies, it can be expected to play a critical role in advancing the practice
      of clinical rheumatology.

PMID- 11508423
TI  - Prognostic factors for radiographic damage in early rheumatoid arthritis: a
      multiparameter prospective study.
AB  - OBJECTIVE: To determine prognostic factors of radiologic damage and radiologic
      progression in early rheumatoid arthritis (RA). METHODS: A cohort of 191 patients
      with RA whose disease duration was shorter than 1 year were prospectively
      followed up for 3 years. Radiologic scores (as determined by Sharp's method,
      modified by van der Heijde) and radiologic progression were used as outcome
      measures. Numerous baseline clinical, laboratory, genetic, and radiographic data
      were obtained. RESULTS: The change in the total radiologic score for the patients
      followed up over 3 years was a mean +/- SD increase of 6.1 +/- 6.2. Radiologic
      progression was observed in 71 of the 172 patients for whom there were data at
      the end of the study. By univariate analysis with Fisher's exact test, radiologic
      scores and progression at followup were closely correlated with the baseline
      values of the erythrocyte sedimentation rate (ESR), C-reactive protein level, IgM
      and IgA rheumatoid factor positivity, antiperinuclear antibody positivity,
      radiologic scores, duration of morning stiffness, and RA-associated HLA-DRB1*04
      genes. No correlation was demonstrated with sex, age, Disease Activity Score,
      swollen or tender joint counts, extraarticular manifestations, Health Assessment
      Questionnaire score, Ritchie Articular Index, patient's assessment of pain,
      positivity for anti-heat-shock protein 90-kd antibodies, anticalpastatin
      antibodies, anti-RA33 antibodies, antinuclear antibodies, YKL-40, or antikeratin
      antibodies, and HLA-DRB1*01 genes. The logistic regression analysis revealed that
      the only baseline values that were predictive of the 3-year radiologic scores
      were IgM rheumatoid factor positivity, DRB1*04 genes, pain score, and total
      radiologic score. Progression of joint damage was predicted by the ESR, IgM
      rheumatoid factor positivity, DRB1*04 genes, and erosions score at baseline.
      CONCLUSION: Prognostic factors for radiographic damage in early RA were
      identified. A combination of these baseline values allowed us to draw up a
      predictive arithmetic score that could be used to predict radiologic damage at 3
      years and radiologic progression in individual patients.

PMID- 11508424
TI  - Synovial tissue protease gene expression and joint erosions in early rheumatoid
      arthritis.
AB  - OBJECTIVE: To relate the expression of proteases in the lining and sublining
      layers of the synovial membrane to the rate of joint damage during 1 year in
      patients with early inflammatory arthritis. METHODS: Samples of synovial membrane
      were obtained by closed-needle biopsy or needle arthroscopy from inflamed knees
      of 20 patients with early inflammatory polyarthritis (mean disease duration 9.6
      months, range 2 weeks to 18 months). Expression of matrix metalloproteinase 1
      (MMP-1), cathepsin B (CB), and cathepsin L (CL) was examined using in situ
      hybridization. Immunohistochemistry was used to identify infiltrating mononuclear
      cell populations. Radiographs of the hands and feet, performed at presentation
      and after 1 year, were evaluated for the development of new erosions. RESULTS:
      Twelve patients had rheumatoid arthritis (RA), 6 had psoriatic arthritis (PsA), 1
      had gout, and 1 had an undifferentiated arthritis. Six patients had erosions at
      presentation. Eleven patients (10 with RA, 1 with PsA) demonstrated at least 1
      new erosion after 1 year of followup. MMP-1, CB, and CL messenger RNA (mRNA) were
      expressed in the synovial membrane of all patients and were present throughout
      the lining layer, as well as in perivascular cellular infiltrates and endothelial
      cells in the sublining layer. In the lining layer, the mean percentages of
      protease mRNA-positive cells per high-power field were higher in those patients
      who developed new joint erosions than in those without evidence of joint damage.
      A similar pattern was observed in the sublining layer, where mean numbers of
      protease mRNA-positive cells were also greater in patients with new joint
      erosions. There were significant differences between the two groups in MMP-1 mRNA
      expression in both the lining and sublining layers (P = 0.0007 and P = 0.0027,
      respectively), as well as in sublining layer CL mRNA expression (P = 0.017), but
      not in CB mRNA expression. Numbers of lining layer CD68+ cells correlated
      positively with lining layer MMP-1 mRNA expression (P = 0.043) and with the
      development of new joint erosions (P = 0.002). CONCLUSION: The detection of MMP
      1, CB, and CL in the synovium soon after the onset of symptoms highlights the
      potential for early joint destruction in patients with RA. High levels of MMP-1
      mRNA expression in the lining layer distinguished patients with more rapidly
      progressive erosive disease. This is the first study to demonstrate features of
      early synovial pathophysiology that may identify patients at increased risk of
      developing new joint erosions.

PMID- 11508425
TI  - Production of cytokines, vascular endothelial growth factor, matrix
      metalloproteinases, and tissue inhibitor of metalloproteinases 1 by tenosynovium
      demonstrates its potential for tendon destruction in rheumatoid arthritis.
AB  - OBJECTIVE: To investigate the role of proinflammatory cytokines, vascular
      endothelial growth factor (VEGF), matrix metalloproteinases (MMPs), and tissue
      inhibitor of metalloproteinases 1 (TIMP-1) in the destruction of tendons by
      tenosynovium in rheumatoid arthritis (RA). METHODS: Synovial specimens were
      obtained from encapsulating tenosynovium (n = 17), invasive tenosynovium (n =
      13), and wrist joints (n = 17) in 18 RA patients undergoing wrist extensor
      tenosynovectomy. Synovial membrane cells were dissociated from connective tissue
      by enzyme digestion and cultured in vitro for 48 hours, and harvested
      supernatants were assayed for the cytokines tumor necrosis factor alpha
      (TNFalpha) and interleukin-6 (IL-6), VEGF, MMPs 1, 2, 3, and 13, and TIMP-1 by
      enzyme-linked immunosorbent assay. Gelatin zymography was performed to
      demonstrate enzyme activity. Statistical analysis was performed using Student's
      paired 2-tailed t-tests for parametric data and the Wilcoxon signed rank test for
      nonparametric data. RESULTS: MMP-1 and MMP-13 levels were approximately 2.5-fold
      higher in invasive tenosynovium compared with encapsulating tenosynovium. Levels
      of MMP-2 were approximately 1.5-fold higher in invasive tenosynovium compared
      with both encapsulating tenosynovium and wrist joint synovium. MMP-13 (P = 0.009)
      and IL-6 (P = 0.03) levels were significantly lower in encapsulating tenosynovium
      compared with wrist joint synovium. Levels of VEGF, TIMP-1, TNFalpha, and MMP-3
      were similar in all synovial sample groups. Zymography demonstrated enzyme
      activity in all synovium samples from all 9 patients assessed. CONCLUSION:
      Tenosynovium produces proinflammatory cytokines and proteolytic enzymes that are
      important in the tissue degradation seen in RA. Increased production of the
      enzymes MMP-1, MMP-2, and MMP-13 by invasive tenosynovium suggests a possible
      explanation for the worse prognosis and increased rupture rate associated with
      invasive tenosynovitis in RA. Production of VEGF by tenosynovium suggests that
      angiogenesis may have a role in tenosynovial proliferation and invasion of
      tendons.

PMID- 11508426
TI  - Corticotropin-releasing hormone signaling in synovial tissue from patients with
      early inflammatory arthritis is mediated by the type 1 alpha corticotropin
      releasing hormone receptor.
AB  - OBJECTIVE: Elevated levels of corticotropin-releasing hormone (CRH) are produced
      locally in inflamed human synovial tissue, and previous observations indicate a
      role for CRH in the pathogenesis of inflammatory joint disease. To further
      elucidate the biologic role of CRH at peripheral sites, we examined the
      expression of known CRH receptor subtypes in inflamed human synovium and compared
      the expression patterns in normal synovium. METHODS: Immunohistochemical analysis
      was used to confirm enhanced expression of specific CRH receptor subtypes in
      rheumatoid arthritis (RA) and psoriatic arthritis (PsA) synovium.
      Immunofluorescence double-labeling was used to further characterize CRH receptor
      expressing cells. Reverse transcriptase-polymerase chain reaction analysis was
      performed to examine CRH receptor subtype messenger RNA (mRNA) expression in RA,
      PsA, and normal synovial tissue. In addition, CRH receptor expression was
      examined in isolated synovial endothelial cells and synoviocytes. RESULTS:
      Selective up-regulation of CRH receptors in inflamed synovial tissue indicated
      that CRH functions locally, in an autocrine/paracrine receptor-mediated manner.
      Immunoreactive CRH receptor type 1 (CRH-R1) was expressed abundantly on vascular
      endothelial cells and discrete perivascular cell populations, identified as mast
      cells. In all samples of inflamed synovium studied, CRH-R1alpha mRNA was
      detected; however, we were unable to identify CRH-R1beta or any CRH-R2 isoforms
      in samples from the same cohort of, patients. CRH receptor subtype expression in
      separated synovial cell populations revealed a pattern of staining similar to
      that seen in vivo. In contrast, neither CRH receptor subtype was expressed in
      normal synovial tissue. CONCLUSION: Our findings suggest that CRH signaling, via
      CRH-R1alpha, may play a role in both the vascular changes and the pathologic
      mechanisms associated with joint inflammation in human arthritis.

PMID- 11508427
TI  - The clinical meaning of functional outcome scores in children with juvenile
      arthritis.
AB  - OBJECTIVE: The Childhood Health Assessment Questionnaire (CHAQ) is the most
      widely used measure of function in childhood arthritis and yields a score of 0
      (no disability) to 3 (very severe disability). This study ascertained the cutoff
      levels for CHAQ scores that represent no, mild, moderate, and severe disability,
      to determine the minimal clinically important change in scores and to determine
      whether the minimal important change in scores is similar for parent-reported
      assessments and the self-assessments provided by their older children. METHODS:
      One hundred thirty-six parents of children with arthritis were interviewed. They
      were asked to complete the CHAQ by assessing their child's functional status
      under 3 categories: current health, a hypothetical small improvement, and a
      hypothetical small worsening. They also completed a categorical scale of
      subjective disability. Those children who were > or = 10 years old also completed
      the CHAQ interview separately. RESULTS: The pediatric patients had mostly no,
      mild, or moderate disability. For those children rated as having no disability,
      the median CHAQ score was 0. The median CHAQ scores corresponding to mild, mild
      to-moderate, and moderate disability were 0.13, 0.63, and 1.75, respectively. The
      minimal clinically important improvement was a reduction in score of 0.13. The
      minimal clinically important deterioration was a median change in score of 0.75.
      This discrepancy may be due to the ceiling effect seen with the CHAQ. There were
      no significant differences when the children assessed themselves. CONCLUSION:
      Clinicians, as well as researchers setting protocols, should aim for a mimimum
      improvement of 0.13 in the CHAQ score when treating pediatric patients with
      arthritis.

PMID- 11508428
TI  - Juvenile arthritis and autoimmunity to type II collagen.
AB  - OBJECTIVE: Joint inflammation in juvenile rheumatoid arthritis (JRA) is sometimes
      associated with an autoimmune response to type II collagen (CII), a cartilage
      specific protein. To test the hypothesis that down-regulation of autoimmunity to
      CII can be accomplished in JRA by oral administration of CII, an open-label study
      of CII was performed in 9 patients with JRA. METHODS: Seven rheumatoid factor
      negative JRA patients with polyarticular disease and 2 JRA patients with
      pauciarticular disease (1 with early onset and 1 with late onset) were treated
      for 3 months with oral bovine CII. Patients were examined for disease activity
      and underwent routine laboratory testing at monthly intervals. Two of the
      patients had flares of disease when treatment was discontinued, and these
      patients were re-treated for an additional 3 months. To test the hypothesis that
      oral tolerance induces an immune deviation of T cells, peripheral blood
      mononuclear cells from patients were collected before and after treatment and
      cultured with CII. Supernatants and RNA were collected and analyzed for the
      presence of various cytokines. RESULTS: Eight patient trials met the criteria for
      clinical improvement outlined by Giannini and coworkers in 1997. None of the
      patients had any side effects from the treatment. In 6 of the 8 patients who
      improved, interferon-gamma production decreased after oral CII therapy,
      correlating with clinical improvement, while 6 patients had increases in levels
      of transforming growth factor beta3. CONCLUSION: These results are encouraging.
      The possible beneficial effect of oral CII in JRA merits further investigation.

PMID- 11508429
TI  - A novel 5'-flanking region polymorphism of macrophage migration inhibitory factor
      is associated with systemic-onset juvenile idiopathic arthritis.
AB  - OBJECTIVE: To determine if polymorphisms of the macrophage migration inhibitory
      factor (MIF) gene are associated with systemic-onset juvenile idiopathic
      arthritis (JIA). METHODS: Denaturing high-performance liquid chromatography was
      used to screen for the MIF gene in 32 healthy Caucasian subjects. One hundred
      seventeen UK Caucasian patients with systemic-onset JIA and 172 unrelated healthy
      UK Caucasian controls were genotyped for a single-nucleotide polymorphism (SNP)
      identified in the 5'-flanking region of the gene, using polymerase chain reaction
      restriction fragment length analysis. RESULTS: A G-to-C transition was identified
      at position -173 of the MIF gene. The presence of a C at -173 creates an
      activator protein 4 transcription factor binding site. Allele and genotype
      frequencies differed significantly between the patients and controls for the MIF
      173 polymorphism. Individuals possessing a MIF-173*C allele have an increased
      risk of systemic-onset JIA (36.8% versus 20.3%) (odds ratio 2.3, 95% confidence
      interval 1.34-3.86; P = 0.0005). CONCLUSION: This is the first report of a SNP in
      the MIF gene. This polymorphism is associated with systemic-onset JIA.

PMID- 11508430
TI  - Effect of alignment of the medial tibial plateau and x-ray beam on apparent
      progression of osteoarthritis in the standing anteroposterior knee radiograph.
AB  - OBJECTIVE: Previous studies of knee osteoarthritis (OA) have yielded variable
      estimates of the rate of joint space narrowing (JSN) in the standing
      anteroposterior (AP) radiograph, due largely to longitudinal changes in the
      alignment of the medial tibial plateau (MTP) and x-ray beam. To characterize this
      bias, we examined serial radiographs of subjects with knee OA in population-based
      and clinical OA cohorts from 3 locations in the United States and the United
      Kingdom. METHODS: Radiographic features of knee OA (e.g., osteophytosis, JSN) and
      MTP alignment in 428 OA knees were evaluated by consensus of 2 readers. Alignment
      was considered satisfactory if the anterior and posterior margins of the MTP were
      superimposed within 1 mm. Readers were blinded to subject identity, and films
      were read in random order. The minimum medial joint space width was also measured
      manually (standard error of repeated measurements 0.20 mm) in serial knee images.
      RESULTS: Only 14% of serial radiographs exhibited alignment of the MTP in both
      images. In OA knees with satisfactory alignment in both images, the mean rate of
      JSN over 2-3 years (0.26 mm/year) was significantly larger (P = 0.004) than that
      in OA knees with misalignment in 1 or both radiographs and was 86% more rapid
      than the mean JSN in all OA knees. Moreover, the within-group standard deviation
      of JSN was significantly smaller among knees with reproduced alignment of the MTP
      than in knees in which misalignment occurred in 1 or both images (P = 0.006).
      CONCLUSION: Poor standardization of knee positioning in serial standing AP
      radiographs in previous studies of OA progression has obscured the rate and
      variability of articular cartilage loss in subjects with knee OA. True JSN (i.e.,
      JSN that is not attributable to longitudinal changes in the alignment of the MTP
      with the x-ray beam in serial radiographic examinations) may occur more rapidly,
      and with less between-subject variability, than that previously thought to be
      characteristic of knee OA.

PMID- 11508431
TI  - Expression of clusterin in the superficial zone of bovine articular cartilage.
AB  - OBJECTIVE: To investigate the differences between chondrocytes of the superficial
      and underlying zones of articular cartilage at the level of gene expression.
      METHODS: Messenger RNA (mRNA) was isolated from chondrocytes harvested from the
      superficial and deep zones of immature bovine articular cartilage. This mRNA was
      reverse transcribed, radiolabeled, and then each complementary DNA (cDNA) sample
      was used to screen duplicate filters of a bovine chondrocyte cDNA library. By
      comparing autoradiographic signals on matching filter sets, clones exclusively
      expressed in the superficial zone of articular cartilage were isolated and
      characterized further. RESULTS: Of the superficial-specific gene clones isolated,
      25% were found to be a single gene product, clusterin. Northern hybridization was
      used to show that clusterin is expressed specifically in the superficial zone of
      articular cartilage and that its expression is up-regulated in mature cartilage.
      In situ hybridization was used to precisely localize clusterin transcripts in
      articular cartilage, where it was found that clusterin expression was confined to
      the articular surface in both immature and mature samples. CONCLUSION: The
      discovery of clusterin expression at the articular cartilage surface extends
      previous observations that superficial articular chondrocytes are highly
      specialized cells. Clusterin is a multifunctional, secreted glycoprotein that has
      been shown to be expressed in diverse locations that have in common a tissue
      fluid boundary. Additionally, clusterin has been implicated in regulating
      complement activation and cell death in injured and degenerating tissues.

PMID- 11508432
TI  - Anti-Fas-induced apoptosis in chondrocytes reduced by hyaluronan: evidence for
      CD44 and CD54 (intercellular adhesion molecule 1) invovement.
AB  - OBJECTIVE: To investigate the in vitro effect of therapeutic hyaluronan (HA) of
      500-730 kd on anti-Fas-induced apoptosis of chondrocytes from osteoarthritis (OA)
      patients, and to assess its mechanism of action by analyzing the role of the 2 HA
      receptors, CD44 and CD54 (intercellular adhesion molecule 1 [ICAM-1]). METHODS:
      Chondrocytes isolated from human OA knee cartilage were cultured and the effect
      of HA on both spontaneous and anti-Fas-induced apoptosis was evaluated. Apoptosis
      was analyzed by JAM test (for quantitative analysis of fragmented DNA), cell
      death detection immunoassay (for quantitative analysis of oligonucleosome), TUNEL
      assay, and electron microscopy. Blocking experiments with anti-CD44 and anti-CD54
      alone or in combination were performed to investigate the HA mechanism of action.
      RESULTS: Both quantitative tests demonstrated that anti-Fas significantly induced
      apoptosis of isolated OA chondrocytes. HA at 1,000 microg/ml significantly
      reduced the anti-Fas-induced apoptosis of chondrocytes but did not affect
      spontaneous chondrocyte apoptosis. These data were also confirmed by TUNEL
      staining and by electron microscopy morphologic evaluation. The antiapoptotic
      effects of HA on anti-FAS-induced chondrocyte apoptosis were significantly
      decreased by both anti-CD44 (mean +/- SD 57 +/- 12% inhibition) and anti-ICAM-1
      (31 +/- 22% inhibition). The mixture of the 2 antibodies had an additive effect,
      since the rate of inhibition increased to 87 +/- 13%. CONCLUSION: These data
      demonstrate that 500-730-kd HA exerts an antiapoptotic effect on anti-FAS-induced
      chondrocyte apoptosis by binding its specific receptors (CD44 and ICAM-1).
      Furthermore, this HA fraction may be able to slow down chondrocyte apoptosis in
      OA by regulating the processes of cartilage matrix degradation.

PMID- 11508433
TI  - Formation and phenotype of cell clusters in osteoarthritic meniscus.
AB  - OBJECTIVE: To determine the histologic changes that accompany the formation of
      cell clusters during the early stages of osteoarthritis development in the
      meniscus, and to characterize the expression phenotype of these cells. METHODS:
      Histologic sections of medial menisci from normal and anterior cruciate ligament
      (ACL)-deficient rabbit knees were immunolabeled with monoclonal antibodies for
      vimentin to highlight the cytoskeleton of meniscal cells, Ki-67 to identify
      proliferating cells, and type X collagen to evaluate changes in the cell
      expression phenotype. Tissue mineralization was assessed by specific staining
      with alizarin red. RESULTS: Following ACL transection, there was an alteration in
      the normal interconnected network of meniscal cells in the fibrocartilaginous
      region of the tissue. This led to isolation of islands of cells within the
      extracellular matrix of the meniscal tissue. These islands of cells displayed 3
      different morphologies based on cell composition: 1) stellate cells, 2) stellate
      as well as round cells, and 3) round cells. Islands composed solely of round
      cells were more prominent in the latter stages following ACL transection, and the
      size of these islands increased with time, apparently as the result of cell
      proliferation. These islands of cells corresponded to the "clusters" previously
      described in osteoarthritic cartilage. Strong expression of type X collagen
      colocalized with the deposition of calcium within the meniscal regions enriched
      with cell clusters. CONCLUSION: Based on the observed changes in cell
      distribution, morphology, and cell proliferation as well as the previous
      detection of apoptosis in similar studies of rabbit knee joints, we propose a
      model for the development of cell clusters in the osteoarthritic meniscus. The
      morphologic appearance as well as the type X collagen expression phenotype of the
      meniscal cells forming the clusters is similar to that of hypertrophic
      chondrocytes. These findings provide a basis for understanding the origin of cell
      clusters in other joint connective tissues, such as osteoarthritic cartilage.

PMID- 11508434
TI  - Alternative messenger RNA splicing and enzyme forms of cathepsin B in human
      osteoarthritic cartilage and cultured chondrocytes.
AB  - OBJECTIVE: In previous studies, we suggested that cathepsin B, which is present
      at sites of cartilage remodeling in osteoarthritis (OA), may act as an antagonist
      of cartilage repair, an enhancer of the action of metalloproteinases, and a
      mediator of cartilage neovascularization and mineralization. Alternative splicing
      of cathepsin B pre-messenger RNA (pre-mRNA) and/or mRNA overexpression is a
      plausible regulatory mechanism. In the present study, we investigated the
      abundance of cathepsin B transcripts and the properties of cathepsin B protein in
      normal and OA cartilage, osteophytes, and cultured chondrocytes. METHODS:
      Cathepsin B mRNA splice variants containing the full-length transcript (CB) and
      the variants lacking either exon 2 (CB[-2]) or lacking exons 2 and 3 (CB[-2,3])
      were measured by semiquantitative reverse transcription-polymerase chain reaction
      (RT-PCR) and Northern blot assays and were localized by in situ RT-PCR. Cathepsin
      B protein was analyzed by electrophoretic, Western blot, and chromatographic
      methods. RESULTS: The relative content of CB, CB(-2), and CB(-2,3) varied
      considerably in OA cartilage and osteophytes, with less variation in normal
      cartilage. The mean cathepsin B mRNA level was significantly higher in OA
      cartilage and osteophytes than in normal cartilage. Normal cultured chondrocytes
      attained cathepsin B mRNA levels similar to those in OA cartilage. Enzyme
      overexpression resulted in the secretion of procathepsin B, followed by
      activation to the proteolytically active form. CONCLUSION: The high levels of CB
      and CB(-2) are consistent with an overproduction of secreted procathepsin B in
      OA. Up-regulation of chondrocyte cathepsin B, which takes place at both the
      transcriptional and the translational level, suggests a leading role of the
      enzyme in the progression of OA.

PMID- 11508435
TI  - Risk of congenital complete heart block in newborns of mothers with anti-Ro/SSA
      antibodies detected by counterimmunoelectrophoresis: a prospective study of 100
      women.
AB  - OBJECTIVE: To assess the true prevalence of congenital complete heart block
      (CCHB) in infants of anti-Ro/SSA-positive women known to have connective tissue
      disease (CTD) and, secondarily, to evaluate the prevalence of other
      electrocardiographic abnormalities in these newborns at birth. METHODS: A
      prospective study was conducted in 4 referral hospitals. One hundred anti-Ro/SSAA
      positive mothers were followed up before they became pregnant and during the
      index pregnancy. Counterimmunoelectrophoresis and immunoblotting were used to
      test for antibodies to extractable nuclear antigens. RESULTS: Of the 100 women
      with anti-Ro/SSA antibodies, 2 had infants who developed CCHB in utero (2%). The
      CCHB was detected at 22 weeks and 20 weeks, respectively. One of the 2 mothers
      had primary Sjogren's syndrome (SS), and the other had undifferentiated CTD
      (UCTD). No case of CCHB occurred among the infants of 53 mothers with systemic
      lupus erythematosus (SLE). No fetal death occurred due to CCHB. In 2 centers,
      electrocardiography was recorded in 24 unselected newborns, and 4 were found to
      have sinus bradycardia. CONCLUSION: The prevalence of CCHB in newborns of
      prospectively followed up women already known to be anti-Ro/SSA positive and with
      known CTD was 2%. This finding is useful with regard to preconception counseling
      of these women. The risk of delivering an infant with CCHB may be higher in
      mothers with primary SS or UCTD than in those with SLE. Additional
      electrocardiographic abnormalities such as sinus bradycardia and prolongation of
      the QT interval may be present in their children.

PMID- 11508436
TI  - A new type of acquired C1 inhibitor deficiency associated with systemic lupus
      erythematosus.
AB  - Acquired C1 inhibitor (C1-INH) deficiency with consequent angioedema is a rare
      condition that may indicate an underlying lymphoproliferative disorder. The
      defect is caused by increased catabolism, which is often associated with the
      presence of serum autoantibodies to C1-INH. The present report describes 3
      patients with systemic lupus erythematosus who developed typical symptoms of
      acquired angioedema, characterized by recurrent swelling of subcutaneous and
      mucous tissues. The 3 patients demonstrated a major classical pathway-mediated
      complement consumption, with very low levels of C3 antigen and decreased levels
      of C1-INH antigen. Neither antibodies to C1-INH nor associated
      lymphoproliferative disease was found. No patient had clinical and biologic signs
      of lupus activity at the time the angioedema occurred. All patients were treated
      with steroids and exhibited a good response, without relapse of angioedema and
      with normalization of plasma levels of C1-INH. In lupus patients who present with
      an angioedema syndrome, acquired or hereditary angioedema must be sought by
      examining parameters of the classical pathway and levels of C1-INH. Our
      observations suggest the existence of a new form of acquired C1-INH deficiency
      associated with a major classical pathway-mediated complement consumption and
      systemic autoimmunity.

PMID- 11508437
TI  - Calcium-channel blockers for Raynaud's phenomenon in systemic sclerosis.
AB  - OBJECTIVE: Most patients with systemic sclerosis (SSc) have Raynaud's phenomenon
      (RP), which is often more severe than idiopathic RP. This study was a meta
      analysis to determine the efficacy of calcium-channel blockers for the treatment
      of RP in SSc. The primary outcome measures were frequency and severity of
      ischemic attacks, digital skin temperature, patient and physician global
      assessments, and digital ulcers. METHODS: The Cochrane search strategy was used
      to ascertain all trials in all languages. Primary data sources included Medline,
      Current Contents, and the Cochrane Controlled Trials Register. Studies that met
      the inclusion criteria were randomized controlled trials of >2 days' duration
      with a dropout rate of <35%. Twenty-nine studies were found, of which 8
      randomized controlled trials were eligible for inclusion. The total number of
      patients included was small (n = 109). Most trials included primary and secondary
      RP, and the main reasons for trial exclusion were inability to extract subset
      data on SSc patients (18 trials), data published previously (2 trials), and lack
      of a control group (1 trial). Data were abstracted independently by 2 reviewers,
      and either a weighted mean difference (WMD) or a standardized mean difference
      (SMD) was calculated for all continuous outcomes; however, information was not
      available for all outcomes within trials. RESULTS: The WMD of all calcium-channel
      blockers versus placebo (6 trials) and of nifedipine alone versus placebo (5
      trials) for the reduction in the frequency of ischemic attacks over a 2-week
      period was -8.31 (95% confidence interval [95% CI] -15.71, -0.91) and -10.21 (95%
      CI -20.09, -0.34), respectively. The SMD of all calcium-channel blockers versus
      placebo (3 trials) and of nifedipine alone versus placebo (2 trials) for the
      reduction in the severity of ischemic attacks was -0.69 (95% CI -1.21, -0.17) and
      -0.99 (95% CI -1.74, -0.24), respectively. CONCLUSION: Calcium-channel blockers
      for RP in SSc have been tested in several small clinical trials and appear to
      lead to significant clinical improvement in both the frequency and the severity
      of ischemic attacks. Most trials were crossover trials in which order effect was
      not studied. This could have introduced bias. The results of this study suggest
      that the efficacy of calcium-channel blockers in reducing the severity and
      frequency of ischemic attacks in RP secondary to SSc is moderate at best (mean
      reduction of 8.3 attacks in 2 weeks and 35% less severity), and a further large,
      randomized controlled trial needs to be conducted.

PMID- 11508438
TI  - Fetal cell microchimerism in tissue from multiple sites in women with systemic
      sclerosis.
AB  - OBJECTIVE: The realization that fetal cells pass into the maternal circulation
      and can survive for many years has raised the question of whether fetal
      microchimerism can cause subsequent disease in the mother. Available data suggest
      that fetal-maternal transfusion may be related to some autoimmune diseases,
      notably systemic sclerosis (SSc). The goal of the current work was to identify
      and quantify tissue-specific fetal microchimerism in women with SSc. METHODS: We
      analyzed multiple tissue specimens obtained at autopsy from women with SSc as
      well as women who had died of causes unrelated to autoimmunity, using
      fluorescence in situ hybridization to detect the presence of male cells in women
      with sons. Tissues analyzed included adrenal gland, heart, intestine, kidney,
      liver, lung, lymph node, pancreas, parathyroid, skin, and spleen. RESULTS: Male
      cells were observed in tissue from at least 1 site in each woman with SSc and
      were found most frequently in spleen sections. After spleen, male cells were
      observed most frequently in lymph node, lung, adrenal gland, and skin tissue. The
      only tissue type in which male cells were not seen in any patient was pancreatic
      tissue. Male cells were not observed in tissue from women who had died of causes
      unrelated to autoimmunity. CONCLUSION: The results of this study suggest that
      fetal cells migrate from the peripheral circulation into multiple organs in women
      with SSc. All of the women studied had previously given birth to sons, so it is
      likely that these cells are of fetal origin. While the relevance of this finding
      to the pathogenesis of SSc remains to be elucidated, the presence of fetal cells
      in internal organs suggests that they could play a role in disease pathogenesis
      and that they may preferentially sequester in the spleen. The presence of these
      male cells may also be a result of disease, possibly through the migration of
      terminally differentiated and/or progenitor cells to areas of tissue damage.

PMID- 11508439
TI  - Abnormalities in fibrillin 1-containing microfibrils in dermal fibroblast
      cultures from patients with systemic sclerosis (scleroderma).
AB  - OBJECTIVE: To determine if there are abnormalities in fibrillin 1-containing
      microfibrils in the extracellular matrix (ECM) of primary dermal fibroblasts
      explanted from patients with systemic sclerosis (SSc). METHODS: Explanted
      fibroblasts from unaffected skin of 12 SSc patients were used to examine
      fibrillin 1-containing microfibrils by immunofluorescence (IF) using a monoclonal
      antibody (mAb) to fibrillin 1. Metabolic labeling of the fibroblast cultures was
      used to study the synthesis, secretion, and processing of fibrillin 1, as well as
      to observe microfibril formation and stability. Microfibrils elaborated by the
      SSc cells were analyzed by electron microscopy for ultrastructural abnormalities,
      and the results were confirmed by immunoblotting. RESULTS: Control and SSc
      fibroblasts displayed a prominent meshwork of fibrillin 1-containing microfibrils
      when visualized by IF using a fibrillin 1 mAb. Paradoxically, metabolic studies
      indicated a paucity of fibrillin 1 in the ECM in the majority of the SSc
      fibroblast strains. Subsequent rotary-shadowed electron microscopy revealed
      reduced amounts of and ultrastructural abnormalities in the microfibrils
      elaborated by all strains of SSc cells. Immunoblots confirmed the lack of the
      high molecular weight form of fibrillin 1 in the SSc fibroblasts of Choctaw
      American Indians. Finally, in vitro studies indicated that the amount of
      fibrillin 1 in the ECM of SSc cells diminished at a faster rate than the amount
      of fibrillin 1 in the ECM of control cells with time. CONCLUSION: Although SSc
      fibroblasts assemble microfibrils, these microfibrils are unstable, suggesting
      that an inherent defect of fibrillin 1-containing microfibrils may play a role in
      the pathogenesis of SSc.

PMID- 11508440
TI  - Evidence of 5-lipoxygenase overexpression in the skin of patients with systemic
      sclerosis: a newly identified pathway to skin inflammation in systemic sclerosis.
AB  - OBJECTIVE: Leukotrienes are a family of arachidonic acid derivatives with potent
      proinflammatory and profibrotic properties, and 5-lipoxygenase (5-LOX) catalyzes
      two key steps in the leukotriene biosynthetic pathway. Since inflammatory cell
      infiltrates and excessive fibrosis are hallmarks of systemic sclerosis (SSc) skin
      lesions, we undertook the present study to investigate the expression of 5-LOX in
      skin biopsy specimens from patients with SSc. METHODS: Expression of 5-LOX in
      skin sections from 10 SSc patients and 8 healthy controls was examined by in situ
      hybridization with specific riboprobes and by immunohistochemistry analysis with
      5-LOX monoclonal antibodies. Synthesis of 5-LOX by cultured dermal fibroblasts
      from 7 patients with SSc and 4 controls was measured by fluorescence-activated
      cell sorter analysis. In addition, concentrations of leukotriene B4 (LTB4) and
      LTE4 in fibroblast supernatants after stimulation were determined using enzyme
      immunoassays. RESULTS: Expression of 5-LOX was found in all skin sections from
      SSc patients as well as from controls. However, the number and percentage of 5
      LOX-positive cells were significantly higher in SSc skin sections compared with
      control sections. Expression of 5-LOX was seen in cells within perivascular
      inflammatory infiltrates as well as in fibroblasts throughout the skin. The
      experiments with cultured skin fibroblasts revealed that 5-LOX was constitutively
      expressed in these cells, which resulted in the production of leukotrienes after
      cell stimulation. Whereas no difference was found for LTE4, SSc fibroblasts
      produced significantly higher amounts of LTB4 after stimulation, compared with
      healthy control fibroblasts. CONCLUSION: The results of this study suggest that
      the 5-LOX pathway may be of significance in the pathogenesis of SSc and may
      represent a target for new treatment strategies.

PMID- 11508441
TI  - Ankylosing spondylitis assessment group preliminary definition of short-term
      improvement in ankylosing spondylitis.
AB  - OBJECTIVE: To develop criteria for symptomatic improvement in patients with
      ankylosing spondylitis (AS), using outcome domain data from placebo-controlled
      clinical trials of nonsteroidal antiinflammatory drugs (NSAIDs). METHODS: Patient
      data from 5 short-term, randomized, controlled trials were used to assess
      equivalence, reliability, and responsiveness of multiple items in the 5 outcome
      domains for AS treatment: physical function, pain, spinal mobility, patient
      global assessment, and inflammation. At least one measure per domain was
      responsive (standardized response mean of > 0.5), except for the spinal mobility
      domain, which was omitted from the criteria. We developed and tested candidate
      improvement criteria in a random two-thirds subset from the 3 largest trials and
      used the remaining one-third for validation. These 3 largest trials included 923
      patients (631 receiving NSAIDs, 292 in placebo groups). We selected the multiple
      domain definition that best distinguished NSAID treatment from placebo by chi
      square test and that had a placebo response rate of < or = 25%. RESULTS:
      Candidate definitions were changes in single domains and in multiple measure
      indices, as well as combinations of improvements in multiple domains. Worsening
      in a domain was defined as a change for the worse of > or = 20% and a net change
      for the worse of > or = 10 units on a scale of 0-100. Partial remission (for
      comparison purposes) was defined as an end-of-trial value of < 20/100 in each of
      the 4 domains. Among 20 candidate criteria, change of > or = 20% and > or = 10
      units in each of 3 domains and absence of worsening in the fourth discriminated
      best in the development subset (51% of patients improved with NSAIDs, 25% with
      placebo; chi2 = 36.4, P < 0.001). Results were confirmed in the validation
      subset. Almost all patients satisfying the definition of partial disease
      remission at the end of the trial had also improved by this criterion. Among all
      923 patients, improvement rates using this criterion were 49% for NSAID-treated
      patients and 24% for placebo-treated patients. CONCLUSION: Although further
      validation using data from new trials is still needed, we conclude that we have
      developed a clinically valid, easy-to-use measure of short-term improvement in
      AS.

PMID- 11508442
TI  - Improved differentiation between Churg-Strauss syndrome and Wegener's
      granulomatosis by an artificial neural network.
AB  - OBJECTIVE: To examine the operating characteristics of the American College of
      Rheumatology (ACR) classification criteria for Churg-Strauss syndrome (CSS) and
      Wegener's granulomatosis (WG), and to develop and validate improved criteria for
      distinguishing CSS from WG. METHODS: The ACR classification criteria for WG and
      CSS were applied to 40 consecutive CSS patients age- and sex-matched with 40
      patients with WG. Forty-three clinical, laboratory, and biopsy parameters were
      assessed. Artificial neural networks (ANNs) were trained and tested with all 43
      parameters (set A) and with 15 solely clinical parameters documented at the
      initial manifestation of the disease (set B). The ANNs were trained with data
      from the first 27 CSS and 27 WG patients and validated with data from the next 13
      consecutive CSS and 13 WG patients. To compare the ANNs with established methods,
      traditional format and classification tree criteria were generated using the same
      data sets. RESULTS: Fourteen of 40 CSS patients fulfilled the ACR criteria for
      WG, while 4 WG patients met the ACR criteria for CSS. The ANN, in contrast,
      reliably distinguished all CSS cases from WG cases (parameter set A, accuracy
      100%). For parameter set B, the ANN achieved an accuracy of 100% in the training
      phase and 96% for validation. The newly formulated traditional format and
      classification tree criteria reached an accuracy of 81% and 88%, respectively.
      CONCLUSION: The ACR criteria for WG do not reliably differentiate between CSS and
      WG (specificity 65%). An ANN, however, could be trained to correctly allocate all
      but 1 patient on the basis of clinical data. Indeed, the ANN applied in this
      study proved superior to established methods of classification. We suggest that
      an ANN may be effectively applied in the classification of systemic vasculitides.

PMID- 11508443
TI  - Inhibitor of nuclear factor kappaB kinase beta is a key regulator of synovial
      inflammation.
AB  - OBJECTIVE: Inhibitor of nuclear factor kappaB kinase beta (IkappaB kinase beta,
      or IKKbeta) has emerged as a key regulator of the transcription factor nuclear
      factor kappaB (NF-kappaB). Since IKKbeta could have both pro- and
      antiinflammatory activity, we examined whether its constitutive activation was
      sufficient to cause a chronic inflammatory disease such as rheumatoid arthritis.
      METHODS: Normal Lewis rats were evaluated for paw swelling by plethysmometry and
      histologic assessment after intraarticular injection of an adenoviral construct
      encoding the IKKbeta wild-type gene (Ad.IKKbeta-wt); controls received an
      adenoviral construct encoding green fluorescent protein (Ad.GFP). The rats were
      killed after 7 days. Additionally, rats were killed 48 hours after intraarticular
      injection of Ad.IKKbeta-wt or Ad.GFP for studies of IKK activity and NF-kappaB
      binding. For studies of the effects of inhibition of IKKbeta activity, Lewis rats
      were immunized with Mycobacterium tuberculosis in mineral oil. The ankle joints
      were injected on day 12 with an adenoviral construct encoding IKKbeta K-->M
      (dominant negative, IKKbeta-dn) or Ad.GFP. We evaluated paw swelling and NF
      kappaB expression on day 25. RESULTS: Intraarticular gene transfer of IKKbeta-wt
      into the joints of normal rats resulted in significant paw swelling and
      histologic evidence of synovial inflammation. Increased IKK activity was
      detectable in the IKKbeta-wt-injected ankle joints, coincident with enhanced NF
      kappaB DNA binding activity. Intraarticular gene transfer of IKKbeta-dn
      significantly ameliorated the severity of adjuvant arthritis, accompanied by a
      significant decrease in NF-kappaB DNA expression in the joints of Ad.IKKbeta-dn
      treated animals. CONCLUSION: IKKbeta plays a key role in rodent synovial
      inflammation. Intraarticular gene therapy to inhibit IKKbeta activity represents
      an attractive strategy for the treatment of chronic arthritis.

PMID- 11508444
TI  - Effects of low-dose, noncytotoxic, intraarticular liposomal clodronate on
      development of erosions and proteoglycan loss in established antigen-induced
      arthritis in rabbits.
AB  - OBJECTIVE: To assess the clinical and histologic effects of an intraarticular
      application of low-dose (non-cytotoxic) liposomal clodronate in established
      antigen-induced monarthritis (AIA) in rabbits. METHODS: AIA was monitored by
      assessments of joint swelling, C-reactive protein levels, and radiographic
      changes in 17 NZW rabbits for 8 weeks during the course of weekly intraarticular
      injections of liposomal clodronate (0.145 mg/injection, low dose) or "empty"
      liposomes. The contralateral knee was injected with liposome buffer alone as the
      control. End-point analyses included macroscopic joint examination, immuno- and
      TUNEL staining, Safranin O staining/microspectrophotometry, and tumor necrosis
      factor alpha (TNFalpha) convertase enzyme (TACE) inhibition assay. RESULTS:
      Liposomal clodronate-treated rabbits showed a reduction and delay in joint
      swelling during the first 3 injections. Expression of matrix-bound (solubilized)
      TNFalpha, lining cell hyperplasia, and levels of RAM-11+ macrophages were low in
      the synovium of the liposomal clodronate treatment group, but the proportion of
      apoptotic lining cells was not affected. The radiologic score was low at the end
      of weeks 2 and 4, but at 8 weeks, no difference, compared with controls, was
      found in pannus formation or in the extent of joint erosion; also, joint swelling
      was higher than before initiation of treatment. Injections of liposomal
      clodronate prevented cartilage proteoglycan loss, which was significant in the
      superficial zone only. TACE activity was not inhibited by clodronate. CONCLUSION:
      Liposomal clodronate had temporary antiinflammatory and antierosive effects on
      established AIA in rabbits. Over the long-term, the loss of cartilage
      proteoglycans was halted. This observed treatment effect may be related to the
      inhibition of TNFalpha production and processing in the synovium.

PMID- 11508445
TI  - Importance of dose of type II collagen in suppression of collagen-induced
      arthritis by nasal tolerance.
AB  - OBJECTIVE: To determine the influence of the dose of collagen given nasally on
      the induction of specific mucosal tolerance in collagen-induced arthritis.
      METHODS: The severity of clinical arthritis induced in DBA/1 mice was studied
      after the nasal administration (before disease induction) of 1 of 4 doses (across
      a 2-log range) of bovine type II collagen (CII). Parameters of immunity included
      lymphocyte proliferation and cytokine production in vitro in response to antigen
      stimulation, and the production of anticollagen IgG antibody subclasses. RESULTS:
      The 3 highest doses (20, 80, and 320 microg) ameliorated disease severity,
      whereas the lowest dose (5 microg) aggravated disease. These findings correlated
      well with antigen-specific T cell proliferation and cytokine and antibody
      production. T cell proliferation was suppressed by the higher doses of CII,
      whereas the low dose enhanced T cell proliferation, indicating it primed the T
      cells. Suppression of T cell proliferation could be overcome by the addition of
      exogenous interleukin-2 (IL-2) to these cultures. Decreased T cell proliferation
      was associated with suppression of both Th1 (interferon-gamma [IFNgamma]) and Th2
      (IL-4) cytokines and all the subclasses of anticollagen IgG in mice receiving 20,
      80, or 320 microg of collagen. Overall, the highest dose of collagen (320 microg)
      was less effective at suppressing the immune response and disease than the 20
      microg or 80-microg doses. There was an increased production of antibodies of all
      IgG isotypes, and of the Th1-associated cytokines IFNgamma and IL-2, in animals
      that had received the lowest dose of 5 microg collagen nasally. CONCLUSION: Nasal
      administration of antigens is effective in inducing tolerance and reducing
      disease severity, but the effects are dose dependent. Low doses can prime the
      immune system and aggravate disease; high doses may not suppress disease.
      Suppression of the immune response, which correlates with suppression of disease,
      is not obviously associated with a type I to type II T cell switch, but rather
      with an overall suppression of both forms of T cell response, with a potential
      role for anergy of T cells in this process.

PMID- 11508446
TI  - Multipotent mesenchymal stem cells from adult human synovial membrane.
AB  - OBJECTIVE: To characterize mesenchymal stem cells (MSCs) from human synovial
      membrane (SM). METHODS: Cell populations were enzymatically released from the SM
      obtained from knee joints of adult human donors and were expanded in monolayer
      with serial passages at confluence. Cell clones were obtained by limiting
      dilution. At different passages, SM-derived cells were subjected to in vitro
      assays to investigate their multilineage potential. Upon treatments, phenotypes
      of cell cultures were analyzed by histo- and immunohistochemistry and by
      semiquantitative reverse transcription-polymerase chain reaction for the
      expression of lineage-retated marker genes. RESULTS: SM-derived cells could be
      expanded extensively in monolayer, with limited senescence. Under appropriate
      culture conditions, SM-derived cells were induced to differentiate to the
      chondrocyte, osteocyte, and adipocyte lineages. Sporadic myogenesis was also
      observed. Five independent cell clones displayed multilineage potential.
      Interestingly, only 1 clone was myogenic. Donor age, cell passaging, and
      cryopreservation did not affect the multilineage potential of SM-derived cells.
      In contrast, normal dermal fibroblasts under the same culture conditions did not
      display this potential. CONCLUSION: Our study demonstrates that human multipotent
      MSCs can be isolated from the SM of knee joints. These cells have the ability to
      proliferate extensively in culture, and they maintain their multilineage
      differentiation potential in vitro, establishing their progenitor cell nature. SM
      derived MSCs may play a role in the regenerative response during arthritic
      diseases and are promising candidates for developing novel cell-based therapeutic
      approaches for postnatal skeletal tissue repair.

PMID- 11508447
TI  - Fibroblast-mediated delivery of growth factor complementary DNA into mouse joints
      induces chondrogenesis but avoids the disadvantages of direct viral gene
      transfer.
AB  - OBJECTIVE: To assess the advantages and disadvantages of a direct adenoviral and
      a cell-mediated approach to the induction of cartilage formation in joints by
      transfer of growth factor genes. METHODS: Adenoviral vectors carrying insulin
      like growth factor 1 (IGF-1) or bone morphogenetic protein 2 (BMP-2)
      complementary DNA were constructed and applied to primary human and murine
      chondrocytes or fibroblasts. Transgene expression was quantified by enzyme-linked
      immunosorbent assay. Direct injection of these vectors or AdLacZ, a reporter gene
      vector, into mouse knee joints was compared with the transplantation of syngeneic
      fibroblasts (infected ex vivo with the same vectors) with respect to virus
      spread, immune response, and cartilage formation by use of histologic,
      immunohistochemical, and molecular analyses. RESULTS: AdIGF-1 and AdBMP-2
      efficiently infected all cell types tested. Human cells secreted biologically
      relevant levels of protein over a period of at least 28 days. Direct transfer of
      AdLacZ into mouse knee joints resulted in positively stained synovial tissues,
      whereas AdLacZ-infected fibroblasts settled on the surface of the synovial
      membranes. Inadvertent spread of vector DNA into the liver, lung, and spleen was
      identified by nested polymerase chain reaction in all mice that had received the
      vector directly; this rarely occurred following fibroblast-mediated gene
      transfer. Direct injection of AdBMP-2 induced the synthesis of new cartilage in
      periarticular mesenchyme, accompanied by extensive osteophyte formation. When
      AdBMP-2 was administered by injecting ex vivo-infected fibroblasts, cartilage
      formation was observed only in regions near the injected cells. AdIGF-1 treatment
      did not lead to morphologic changes. Importantly, fibroblast-mediated gene
      transfer avoided the strong immune response to adenovirus that was elicited
      following direct application of the vector. CONCLUSION: Our results indicate that
      cell-mediated gene transfer provides sufficient BMP-2 levels in the joint to
      induce cartilage formation while avoiding inadvertent vector spread and immune
      reactions.

PMID- 11508448
TI  - A deceptive case of amyloid myopathy: clinical and magnetic resonance imaging
      features.
AB  - Amyloid myopathy is a well-described, increasingly recognized clinical entity.
      Similar to inflammatory myopathies, amyloid myopathy presents with proximal
      muscle weakness and can be associated with elevated levels of muscle enzymes. We
      report the case of a 58-year-old woman who, at presentation to her physician with
      proximal muscle weakness and congestive heart failure, was antinuclear antibody
      positive and had muscle biopsy findings "consistent with inflammatory myopathy."
      She was referred to Johns Hopkins University Medical Center with the diagnosis of
      polymyositis. Further investigation revealed a monoclonal gammopathy, a unique
      patterning of subcutaneous fat reticulation and hypodense bone marrow changes on
      magnetic resonance imaging (MRI), and an endocardial biopsy sample that was
      positive for light chain amyloid deposition. Paraffin sections of the muscle
      biopsy sample from the time of her original presentation were obtained, and Congo
      red staining showed diffuse amyloid deposition throughout the sample, but no
      inflammation. This case not only illustrates that proximal muscle weakness due to
      primary amyloid myopathy (as found in light chain amyloidosis and transthyretin
      amyloidosis) can mimic that of polymyositis, but also shows that unique findings
      on MRI can alert the clinician to the diagnosis of amyloidosis prior to muscle
      biopsy.

PMID- 11508449
TI  - Early hydroxychloroquine macular toxicity.
AB  - This report describes the case of an appropriately dosed patient who developed
      maculopathy <8 years after starting hydroxychloroquine (HCQ) therapy for systemic
      lupus erythematosus. Risk factors and screening for HCQ-associated maculopathy
      are discussed.

PMID- 11508450
TI  - Successful treatment of patients with systemic lupus erythematosus by
      immunoadsorption with a C1q column: a pilot study.

PMID- 11508451
TI  - Increased risk of ankylosing spondylitis among first-born children: comment on
      the article by Baudoin et al.

PMID- 11508452
TI  - The Sapporo criteria for antiphospholipid syndrome: comment on the article by
      Lockshin et al.

PMID- 11508454
TI  - To Professor Dr. Klaus Danzer on his 65th birthday.

PMID- 11508453
TI  - Hepatitis with interface inflammation and IgG, IgM, and IgA anti-double-stranded
      DNA antibodies following infliximab therapy: comment on the article by Charles et
      al.

PMID- 11508455
TI  - Comparison of detection limits in environmental analysis--is it possible? An
      approach on quality assurance in the lower working range by verification.
AB  - Detection limit, reporting limit and limit of quantitation are analytical
      parameters which describe the power of analytical methods. These parameters are
      used for internal quality assurance and externally for competing, especially in
      the case of trace analysis in environmental compartments. The wide variety of
      possibilities for computing or obtaining these measures in literature and in
      legislative rules makes any comparison difficult. Additionally, a host of terms
      have been used within the analytical community to describe detection and
      quantitation capabilities. Without trying to create an order for the variety of
      terms, this paper is aimed at providing a practical proposal for answering the
      main questions for the analysts concerning quality measures above. These main
      questions and related parameters were explained and graphically demonstrated.
      Estimation and verification of these parameters are the two steps to get real
      measures. A rule for a practical verification is given in a table, where the
      analyst can read out what to measure, what to estimate and which criteria have to
      be fulfilled. In this manner verified parameters detection limit, reporting limit
      and limit of quantitation now are comparable and the analyst himself is
      responsible to the unambiguity and reliability of these measures.

PMID- 11508456
TI  - Quantifying the measurement uncertainty of results from environmental analytical
      methods.
AB  - The Eurachem-CITAC Guide Quantifying Uncertainty in Analytical Measurement was
      put into practice in a public laboratory devoted to environmental analytical
      measurements. In doing so due regard was given to the provisions of ISO 17025 and
      an attempt was made to base the entire estimation of measurement uncertainty on
      available data from the literature or from previously performed validation
      studies. Most environmental analytical procedures laid down in national or
      international standards are the result of cooperative efforts and put into effect
      as part of a compromise between all parties involved, public and private, that
      also encompasses environmental standards and statutory limits. Central to many
      procedures is the focus on the measurement of environmental effects rather than
      on individual chemical species. In this situation it is particularly important to
      understand the measurement process well enough to produce a realistic uncertainty
      statement. Environmental analytical methods will be examined as far as necessary,
      but reference will also be made to analytical methods in general and to physical
      measurement methods where appropriate. This paper describes ways and means of
      quantifying uncertainty for frequently practised methods of environmental
      analysis. It will be shown that operationally defined measurands are no obstacle
      to the estimation process as described in the Eurachem/CITAC Guide if it is
      accepted that the dominating component of uncertainty comes from the actual
      practice of the method as a reproducibility standard deviation.

PMID- 11508457
TI  - Uncertainty of measurement. Twenty years afterwards.
AB  - The application of the concept "uncertainty" causes considerable difficulties. In
      this paper an analysis of the intrinsic contradictions of the concept itself and
      its relationship with the statements of metrology is given with the aim of
      establishing possible reasons for these difficulties. As a result of this
      analysis several examples are presented to demonstrate the conflicts of the
      concept and its several statements in the general fundamental notions of
      metrology.

PMID- 11508458
TI  - Resolution of two-way data: theoretical background and practical problem-solving.
      Part 1: theoretical background and methodology.
AB  - This paper reviews recent progress in the resolution of two-way data obtained
      from hyphenated instruments. Special emphasis is placed on the solution of
      practical problems. Methods for estimating the number of chemical components both
      statistically and visually (the first step in solving the resolution problem) and
      methods for resolving the pure profiles (the second step in solving the
      resolution problem) are discussed in detail. To deal with real-world problems,
      pitfalls in the chemometric analysis of the two-way data from the instrumental
      measurements are also pointed out. Applications of methods for solving some
      difficult practical problems in environmental chemistry, pharmaceutical
      chemistry, and physical chemistry will be discussed in the second part of this
      paper.

PMID- 11508459
TI  - Some case studies of skewed (and other ab-normal) data distributions arising in
      low-level environmental research.
AB  - Three general classes of skewed data distributions have been encountered in
      research on background radiation, chemical and radiochemical blanks, and low
      levels of 85Kr and 14C in the atmosphere and the cryosphere. The first class of
      skewed data can be considered to be theoretically, or fundamentally skewed. It is
      typified by the exponential distribution of inter-arrival times for nuclear
      counting events for a Poisson process. As part of a study of the nature of low
      level (anti-coincidence) Geiger-Muller counter background radiation, tests were
      performed on the Poisson distribution of counts, the uniform distribution of
      arrival times, and the exponential distribution of inter-arrival times. The real
      laboratory system, of course, failed the (inter-arrival time) test--for very
      interesting reasons, linked to the physics of the measurement process. The
      second, computationally skewed, class relates to skewness induced by non-linear
      transformations. It is illustrated by non-linear concentration estimates from
      inverse calibration, and bivariate blank corrections for low-level 14C-12C
      aerosol data that led to highly asymmetric uncertainty intervals for the biomass
      carbon contribution to urban "soot". The third, environmentally, skewed, data
      class relates to a universal problem for the detection of excursions above blank
      or baseline levels: namely, the widespread occurrence of ab-normal distributions
      of environmental and laboratory blanks. This is illustrated by the search for
      fundamental factors that lurk behind skewed frequency distributions of sulfur
      laboratory blanks and 85Kr environmental baselines, and the application of robust
      statistical procedures for reliable detection decisions in the face of skewed
      isotopic carbon procedural blanks with few degrees of freedom.

PMID- 11508460
TI  - Multivariate statistical interpretation of coastal sediment monitoring data.
AB  - Multivariate statistical analysis of sediment data (input matrix 122 x 15)
      collected from 122 sampling sites from the western coastline of the USA and
      analyzed for 15 analytes indicates that the data structure could be explained by
      four latent factors. These factors are conditionally named "anthropogenic",
      "organic", "natural", and "hot spots". They explain over 85% of the total
      variance of the data system, which is an acceptable value for the PCA model. The
      receptor models obtained after regression of the mass on the absolute principal
      components scores ensures reliable estimation of the contribution of each
      possible natural or anthropogenic source to the mass of each chemical component.
      It can be concluded that the region of interest reveals a different pattern of
      pollution compared with the eastern coastline treated statistically in a previous
      study.

PMID- 11508461
TI  - Quantification of butanol and ethanol in aqueous phases by reflectometric
      interference spectroscopy--different approaches to multivariate calibration.
AB  - This paper presents several methods for analysis of data from reflectometric
      interference spectroscopic measurements (RIfS) of water samples. The set-up
      consists of three sensors with different polymer layers. Mixtures of butanol and
      ethanol in water were measured from 0 to 12,000 ppm each. The data space was
      characterized by principal component analysis (PCA). Calibration and prediction
      were achieved by multivariate methods, e.g. multiple linear regression (MLR),
      partial least squares (PLS) with additional predictors, and quadratic partial
      least squares (Q-PLS), and by use of artificial neural networks. Artificial
      neural networks gave the best results of all the calibration methods used.
      Calibration and prediction of the concentration of the two analytes by artificial
      neural nets were robust and the set-up could be reduced to only two sensors
      without deterioration of the prediction.

PMID- 11508462
TI  - Temperature dependence of the optical properties of CuMoO4.
AB  - CuMoO4 crystals reversibly change their color from green to brown upon heating,
      accompanied by a loss in transmittance. UV/VIS spectroscopic analysis revealed
      that these changes are due to particular electronic properties of the crystal
      instead of its chemical decomposition or structural change. Investigations were
      carried out in the temperature range 23-400 degrees C. The intensive green color
      of the crystal at room temperature is caused by a small transmission window
      between two absorption bands, the band gap of the crystal in the blue and the 3d9
      ->4p absorption of the Cu2+ ions in the red. With increasing temperature the band
      gap shifts towards longer wavelengths, and the crystal changes both color and
      transmittance. Spectroscopic features of the crystal are discussed together with
      the temperature dependence of its electrical resistance. Resistance measurements
      were performed simultaneously to the optical measurements.

PMID- 11508463
TI  - Electrolytic hydride generation atomic absorption spectrometry for the
      determination of antimony, arsenic, selenium, and tin--mechanistic aspects and
      figures of merit.
AB  - This article deals with the electrocatalytic and electrochemical mechanisms of
      hydride formation and their dependence on hydrogen overvoltage. A three-electrode
      arrangement was used to determine the hydrogen overvoltage of different cathode
      materials (Pt, Au, Ag, glassy carbon, Cd, Pb, amalgamated Ag). The applicability
      of these cathode materials was tested for hydride formation using As(III), As(V),
      Sb(III), Sb(V), Se(IV), and Sn(IV). Glassy carbon is the most suitable cathode
      material for hydride generation with As(III), Sb(III), Se(IV), and Sn(IV). Hg-Ag
      is well suited for the production of stibine and arsine. As(III), As(V), Sb(III),
      and Sb(V) were all converted into their hydrides with efficiencies > 90%. A
      detection limit in the range of 0.11-0.13 microg L(-1) for As and Sb (sample
      volume 200 microL) was obtained for cathode materials with a high hydrogen
      overvoltage. The precision of replicate measurements was better than 5%
      calculated as variation coefficient. The accuracy of the presented method was
      verified by analysis of certified reference materials and tissues of cancer
      patients. The recovery rates for As and Se were calculated to be 93-108%.

PMID- 11508464
TI  - Rapid and sensitive determination of radiocesium (Cs-135, Cs-137) in the presence
      of excess barium by electrothermal vaporization-inductively coupled plasma-mass
      spectrometry (ETV-ICP-MS) with potassium thiocyanate as modifier.
AB  - An electrothermal vaporization-inductively coupled plasma-mass spectrometric (ETV
      ICP-MS) method based on selective volatilization of cesium with KSCN as modifier
      has been developed for determination of radiocesium, i.e. 135Cs and 137Cs, in the
      presence of isobaric barium. A 10,000 times excess of barium, which was
      volatilized at a temperature of 1,100 degrees C, resulted only in a 1% signal
      increase in the signal of mass 135 amu. The recommended concentration of KSCN is
      0.3 mM, and pretreatment and volatilization temperatures are 400 degrees C and
      1,100 degrees C, respectively. A ramp time of 1 s is recommeded for the
      volatilization step. The achieved limit of detection for 135Cs is 0.2 pg/mL (10
      microBq/mL) and 4 fg (0.2 microBq) absolute for a sample volume of 20 microL.
      This means a limit of detection for 137Cs of 0.2 pg/mL (0.6 Bq/mL) and of 4 fg
      (0.01 Bq) absolute. Signal variations of 135Cs and 137Cs, respectively, in spiked
      samples with various matrices were investigated.

PMID- 11508465
TI  - Characterization of municipal solid waste incineration (MSWI) bottom ash by
      scanning electron microscopy and quantitative energy dispersive X-ray
      microanalysis (SEM/EDX).
AB  - Scanning electron microscopy (SEM) with energy-dispersive X-ray microanalysis
      (EDX) is frequently used for morphological and qualitative chemical
      characterization of different materials. The applicability of this method for
      phase identification, is, however, often underestimated. The application of
      SEM/EDX for the characterization of different phases in fresh and altered
      municipal-waste incinerator bottom-ash samples with high lateral resolution is
      presented. Polished thin sections were prepared from the samples, but fresh
      fracture surfaces were also used. The EDX analyses were performed by using the
      correction procedures of a conventional standardless ZAF correction, a peak-to
      background ZAF correction, and a correction method for light-element analysis.
      Because of their highly reactive properties the bottom-ash SEM samples require a
      special method of preparation. The method facilitates nondestructive preparation
      of the sensitive bottom-ash alteration phases (e.g. cement phases, hydroxides,
      salts) and their microstructures.

PMID- 11508466
TI  - Direct solid sample analysis of geological samples with SS-GF-AAS and use of 3D
      calibration.
AB  - These results from direct solid-sample trace-element analysis, with 3D
      calibration, follow those of earlier publications. Cd, Cr, Cu, Ni, Pb, and Zn
      have been determined in complex inorganic powder samples, e.g. sediments, soils,
      rocks, and minerals. The measurements were performed with two SS-GF-AAS
      spectrometers which differ in the type of graphite furnace (transverse and
      longitudinal tube) and the background-correction technique (with and without the
      Zeeman system). The performance of the 3D calibration method was optimized by
      systematic investigation and the 2D- and 3D calibration techniques were compared.
      Another feature is the determination of confidence limits of the 3D calibration.
      This calibration error was calculated by the statistical bootstrap method. The
      results of calibration experiments and the precision and accuracy of the
      determination of trace elements in CRMs show that 3D calibration becomes
      increasingly essential as the refractory character of the analyte increases.
      Although there are large differences between the state of development and
      technical performance of the instruments used, 3D-calibration works with both SS
      GF-AAS spectrometers.

PMID- 11508467
TI  - Speciation of beryllium, nickel, and vanadium in soil samples from Csepel Island,
      Hungary.
AB  - Sequential leaching methods have been used for the speciation of Be, Ni, and V in
      five soil samples from Csepel Island on the Danube river located near an oil
      fired power plant. The concentrations of the elements of the extracts were
      determined by inductively coupled plasma mass spectrometry. The total efficiency
      (the sum of the extracted metals divided by metal fraction which is soluble in
      aqua regia) of the five-step method was always higher. The difference for Ni was
      considerable, because of the high abundance of Ni found in the moderately
      reducible fraction, which is absent from the three-step method. The sum of the
      mobile species (exchangeable, carbonatic, and easily reducible) determined by
      both methods, were in reasonable agreement; this was not so for the individual
      fractions. There were greater differences between the non-mobile fractions
      (moderately reducible and oxidizable), because of the presence or absence of the
      moderately reducible fraction. For both methods there was good correlation
      between the oxidizable fraction and the organic matter content of the soils.

PMID- 11508468
TI  - Solid-phase reactors in sequential injection analysis. Determination of manganese
      (II) in tap water and effluent streams using a solid-phase lead(IV) dioxide
      reactor in a sequential injection system.
AB  - The determination of manganese(II) in tap water and effluent streams, using a
      solid-phase reactor incorporated into a sequential injection system was
      investigated. Mn2+-ions in samples injected into a carrier stream, were oxidised
      by solid lead(IV) dioxide suspended on silica gel beads to form MnO4- -ions which
      were detected spectrophotometrically at 526 nm. The linear range of the system is
      from 1 to 7 mg L(-1) with a detection limit of 0.62 mg L(-1). The proposed system
      is suitable for the determination of manganese(II) in tap and effluent streams at
      a rate of approximately 50 samples per hour with a relative standard deviation of
      better than 3%. Statistical comparison between the proposed sequential injection
      system and a standard ICP method revealed that there is no significant difference
      between the two methods at the 95% confidence level for effluent streams and at
      99.9% for tap water.

PMID- 11508469
TI  - Capillary zone electrophoresis of proteins with poly(2-hydroxyethyl methacrylate)
      coated capillaries: fundamental and applications.
AB  - Fused silica capillaries have been modified by atom-transfer radical
      polymerization (ATRP) to generate covalently bonded polymer films of 2
      hydroxyethyl methacrylate. Because the kinetics of ATRP have mainly been
      investigated in bulk solutions, a GC experiment was set up to examine monomer
      conversion inside narrow-bore capillaries. It was shown that after 1 to 4 h the
      reaction was nearly complete. The coating process was further optimized by
      monitoring EOF, because low EOF indicates high surface coverage. To deal with the
      very low EOF values, a new approach was used to dramatically reduce the
      measurement time by overlaying hydrodynamic flow on the electroosmotic flow. The
      corresponding equations are derived separately in detail. Capillaries were then
      coated under optimum conditions with linear or cross-linked polymer films. The
      EOF was reduced over a wide range of pH values. A long-term reproducibility test
      with both types of functionalization showed that the efficiency of the linear
      polymer coating decreased significantly over time. With cross-linked films,
      however, the efficiency even increased. Relative standard deviations for protein
      migration times were also much lower in cross-linked coated capillaries. Highly
      efficient separations could be performed for basic and acidic proteins in acidic
      media, and for the latter even in basic media.

PMID- 11508470
TI  - Raman spectroscopic surface characterization of cellulose derivatives.
AB  - First results of experiments on the surface characterization of cellulose
      derivatives are presented. Different water contents of the surface of
      microcrystalline cellulose have been investigated by means of Raman spectroscopy,
      SERS, and environmental scanning electron microscopy (ESEM).

PMID- 11508471
TI  - Oncologists' use of quality of life information: results of a survey of Eastern
      Cooperative Oncology Group physicians.
AB  - PURPOSE: Objectives of this study were to obtain data from Eastern Cooperative
      Oncology Group (ECOG) oncologists regarding their views on quality of life (QOL)
      information; perform psychometric testing on the MD-QOL questionnaire, develop a
      model to describe oncologists' willingness to use QOL information and propose
      data-based interventions to facilitate use of QOL information in clinical
      decision-making. METHODS: A self-administered questionnaire, MD-QOL, designed to
      assess physician perspective on QOL information was mailed to a random sample of
      500 oncologists, members of ECOG; 271 responded. RESULTS: Oncologists' attitude,
      current behaviour, knowledge of QOL data, and reported willingness to use QOL can
      be measured using MD-QOL. The attitude, behaviour and willingness scales have
      high internal consistency. Physician attitude and behaviour account for 59% of
      the variance in the willingness to use QOL information. Demographic variables
      influencing physician responses were their primary income source and exposure to
      trials with a QOL component. CONCLUSIONS: This report of ECOG oncologists' views
      on QOL information suggests a model to describe relationship between physician
      willingness to use QOL information on the basis of their attitude and behaviour.
      Data-based interventions are proposed to influence the key variables and thus
      facilitate the incorporation of QOL data in clinical practice.

PMID- 11508472
TI  - Electronic collection of health-related quality of life data: validity, time
      benefits, and patient preference.
AB  - This study sought to validate World Wide Web-compliant software tools used to
      collect health-related quality of life (HRQOL) data, relative to pencil-and-paper
      collection. The RAND-36 general health survey and the Seattle Angina
      questionnaire (SAQ), a disease-specific functional status measure for patients
      with coronary artery disease, were each administered in paper and electronic
      format to 55 consecutive patients visiting the cardiology outpatient clinic of a
      public hospital. All eight sub-scale scores of the RAND-36 (interclass
      correlation coefficient range = 0.54-0.75, p < 0.01) and all five domains of the
      SAQ (interclass correlation coefficient range = 0.84-0.90, p < 0.01) collected
      using the software were significantly correlated with those collected using the
      paper version of questionnaires. Computer literacy, educational level, age, sex,
      and race were not significantly associated with the ability to successfully
      complete the computer-assisted questionnaire. Eighty-two percent of patients
      preferred the computer-assisted administration to paper, and 89% reported that
      they would feel comfortable using the software in the future without any
      technical assistance. This pilot study suggests that HRQOL measures can be
      reliably collected using software operating over the World Wide Web. Data
      collected in this manner are valid and of comparable quality to self-reported,
      HRQOL data obtained via paper survey.

PMID- 11508473
TI  - Comparison of three generic questionnaires measuring quality of life in
      adolescents and adults with cystic fibrosis: the 36-item short form health
      survey, the quality of life profile for chronic diseases, and the questions on
      life satisfaction.
AB  - OBJECTIVE: To compare different generic instruments in measuring quality of life
      and to demonstrate dimensions of quality of life (QL) in patients with cystic
      fibrosis (CF). METHODS: The short-form-36 health survey (SF-36), the quality of
      life profile for chronic diseases (PLC), and the questions on life satisfaction
      (FLZ(M)) were simultaneously employed in a cross-sectional study with 70
      adolescents and adults with CF. The different concepts of the measures were
      compared. Internal consistency (Cronbach's alpha), convergent and construct
      validity (correlation patterns, common factor analysis), and external validity
      (correlations with symptom and pulmonary function scores, with intensity of
      therapy; comparisons with healthy peers) of the three instruments were
      investigated. RESULTS: Similar reliability, but different validity of the
      questionnaires are demonstrated. Seventy-three percent of the total variance
      across the three measures could be explained with a seven-factor-solution: (1)
      physical functioning (19.3% of total variance), (2) mental health (19.3%), (3)
      social integration (7.5%), (4) role function/pain (7.5%), (5) economic/material
      living conditions (7.5%), (6) partnership/family (6.7%) and (7) anxiety (5.2%).
      DISCUSSION: The different validity of the instruments has to be considered in
      chosing a questionnaire appropriate to the purpose of measuring. Shortcomings of
      each instrument can be overcome by multimethod designs and by developing disease
      specific scales.

PMID- 11508474
TI  - Psychological status and the role of coping style after coronary artery bypass
      graft surgery. Results of a prospective study.
AB  - The results of a prospective study in patients who underwent a first coronary
      artery bypass graft operation are presented. The goals of this project consisted
      in assessing the psychological changes during the first year after surgery. For
      that purpose, 330 consecutive patients were recruited. They were assessed by
      means of several psychological scales before and on three occasions after
      surgery. These scales were: the Heart Patients' Psychological Questionnaire
      (HPPQ), the State-Trait Anxiety Scale (STAI), the Symptom Check List (SCL-90),
      the Maastricht Questionnaire (MQ) and the Marlowe Crowne Desirability Scale.
      Furthermore, the study focused on the differential influence of three coping
      styles. The data demonstrate a clear overall improvement in psychological status
      over the first year, more specifically during the first 6 months after CABG.
      Patients were less anxious, less depressed, less exhausted and experienced more
      subjective well-being. However, almost 30% of all patients did not experience
      that average favourable evolution. The final psychological end-state was
      predicted by psychological variables, measured pre-operatively (somatic
      complaints, hostility and dysphoria) and short-term post-operatively (anxiety).
      No single medical variable could predict patients' psychological end-state.
      Finally, the most favourable change was made by patients who display the
      sensitising coping style, resulting in lower anxiety and depression. Health care
      providers, physicians as well as nursing staff and psychologists, should
      therefore use psychodiagnostic tools in order to identify patients at risk for
      negative psychological outcome. Appropriate therapeutic interventions may
      consequently be developed and evaluated in future research.

PMID- 11508475
TI  - Health-related quality of life research and the capability approach of Amartya
      Sen.
AB  - Standardised health-related quality of life questionnaires play an increasing
      role as measures of outcome in the evaluation of health care interventions.
      However, problems can arise when the selected functions or dimensions of such
      standardised measures are not in line with the intervention that is the focus of
      the research. Furthermore, the subjective element of quality of life makes
      standardised questionnaires vulnerable to the coping mechanism, thereby
      decreasing their sensitivity. The capability approach of the economist and
      philosopher Amartya Sen offers a descriptive concept that contributes to a better
      understanding of these problems. This article provides an introduction to the
      ideas of Sen for researchers who wish to go beyond the traditional framework of
      measuring health-related quality of life.

PMID- 11508476
TI  - Elementary school-aged children's reports of their health: a cognitive
      interviewing study.
AB  - There are no standard methods for assessing the quality of young children's
      perceptions of their health and well-being and their ability to comprehend the
      tasks involved in reporting their health. This research involved three cross
      sectional studies using cognitive interviews of 5-11-year-old children (N = 114)
      to determine their ability to respond to various presentations of pictorially
      illustrated questions about their health. The samples had a predominance of
      children in the 5-7-year-old range and families of lower and middle socio
      economic status. The research questions in Study 1 involved children's ability to
      convert their health experiences into scaled responses and relate them to
      illustrated items (n = 35); Study 2 focused on the type of response format most
      effectively used by children (n = 19); and Study 3 involved testing children's
      understanding of health-related terms and use of a specific recall period (n =
      60). The results of Study 1 showed that children identified with the cartoon
      drawing of a child depicted in the illustrated items, typically responding that
      the child was at or near their own age and of the same gender, with no
      differences related to race. Study 2 results indicated that children responded
      effectively to circles of graduated sizes to indicate their response and
      preferred them to same-size circles or a visual analogue scale. Tests of three-,
      four-, and five-point response formats demonstrated that children could use them
      all without confusion. In Study 3, expected age-related differences in
      understanding were obtained. In fact, the 5-year-old children were unable to
      understand a sufficient number of items to adequately describe their health.
      Virtually all children 8 years of age and older were able to fully understand the
      key terms and presentation of items, used the full five-point range of response
      options, and accurately used a 4-week recall period. Six- and seven-year-olds
      were more likely than older children to use only the extreme and middle responses
      on a five-point scale. No pattern of gender differences in understanding or in
      use of response options was found. We conclude that children as young as eight
      are able to report on all aspects of their health experiences and can use a five
      point response format. Children aged 6-7 had difficulty with some health-related
      terms and tended to use extreme responses, but they understood the basic task
      requirements and were able to report on their health experiences. These results
      provide the guidance needed to develop and test a pediatric health status
      questionnaire for children 6-11 years old.

PMID- 11508477
TI  - Health-related quality of life in childhood disorders: a modified focus group
      technique to involve children.
AB  - OBJECTIVES: Qualitative methodology has been under-utilized in child health
      research due to lack of a specific set of instruments. The objective of this
      study was to develop a child-centred qualitative research methodology to
      facilitate direct exploration of health-related quality of life (HRQL) issues and
      to identify the quality of life elements in pre-adolescent children with a
      chronic medical condition. STUDY DESIGN: Purposeful stratified sampling of
      children, ages 6-12, who function in a regular school class, with active epilepsy
      who were assembled in small focus groups. The groups met in four phases and were
      led by moderators who probed preset open questions and activities. RESULTS: The
      study demonstrated that our modified focus groups process was a powerful
      exploratory experience eliciting meaningful and important issues in quality of
      life beyond what parents and health professionals expected, and helped identify
      HRQL elements in childhood epilepsy. CONCLUSION: Modified focus groups are
      appropriate and suitable to explore quality of life issues in pre-adolescent
      children with a chronic medical condition. The process is feasible and
      trustworthy.

PMID- 11508478
TI  - The spanish version of the paediatric asthma quality of life questionnaire
      (PAQLQ): metric characteristics and equivalence with the original version.
AB  - The Paediatric Asthma Quality of Life Questionnaire (PAQLQ), developed by Juniper
      et al., assesses the impact of asthma on children's daily life. It contains 23
      items, covering three dimensions: symptoms, activities limitation and emotional
      function. AIMS: To develop an equivalent Spanish version of the PAQLQ, and to
      assess its measurement characteristics. METHODS: The forward and back-translation
      method was used for the adaptation. A longitudinal study (assessments at the 1st
      and 5th weeks), with patients from the emergency and outpatient departments of
      three Spanish hospitals, was designed to test the properties of the new adapted
      version. At each visit, a trained interviewer administered the PAQLQ, a Global
      Index of Change and a General Health Perception scale. The Peak Expiratory Flow
      Rate (PEFR) was also recorded daily, together with symptoms, during the prior
      week. RESULTS: Ninety-nine patients (66.7% males, 42.4% suffering an
      exacerbation, mean age of 11.3 years) with the following types of asthma were
      evaluated: mild intermittent (31.3%), mild persistent (36.4%), moderate
      persistent (29.3%) and severe persistent (3%). At the 1st visit, the mean pre
      bronchodilator %PEFR was 87.3%. The Cronbach's alpha ranged from 0.86 to 0.95. As
      expected, correlations between the PAQLQ scores, and the Asthma Control Score
      (0.53-0.67), the General Health Perception (0.34-0.55), and the %PEFR (0.44-0.55)
      were moderate. The PAQLQ scores remained unchanged in stable patients while
      increased significantly in those showing improvements. CONCLUSIONS: After a
      standard cross-cultural adaptation process, the Spanish version of the PAQLQ has
      shown to be equivalent to the original, with similar internal consistency
      reliability, validity and sensitivity to clinical changes.

PMID- 11508479
TI  - Translation, cultural adaptation, and initial reliability and multitrait testing
      of the Kidney Disease Quality of Life instrument for use in Japan.
AB  - BACKGROUND: The Kidney Disease Quality of Life instrument (KDQOL) consists of 79
      items: 36 asking about health-related quality of life (HRQOL) in general (the
      Medical Outcomes Study SF-36) and 43 asking about QOL as it is affected by kidney
      disease and by dialysis. AIM: Translation, cultural adaptation and initial
      reliability and multitrait testing of the KDQOL for use in Japan. METHODS:
      Translation and cultural adaptation began with two translations into Japanese,
      two backtranslations into English, and discussions among the translators, the
      project coordinators in Japan, and the developers of the original (US-English)
      version. Focus-group discussions and field testing were followed by analyses of
      test-retest reliability, internal consistency, and convergent and discriminant
      construct validity. RESULTS: All eight of the SF-36 scales met the criterion for
      internal consistency (Cronbach's alpha ranged from 0.73 to 0.92) and were
      reproducible (intraclass correlations between test and retest scores ranged from
      0.60 to 0.82). Of the 10 kidney-disease-targeted scales, only two had alpha
      coefficients of less than 0.70: 'sleep' (0.61) and 'quality of social
      interaction' (0.35). One item on the 'quality of social interaction' scale had a
      very weak correlation with the remainder of that scale (r = 0.10). Eliminating
      that item from scoring increased the alpha coefficient of the scale from 0.35 to
      0.64. All three items on the 'quality of social interaction' scale had very
      strong correlations with other scales. CONCLUSIONS: First, in Japanese patients
      receiving dialysis the SF-36 scales are internally consistent and their scores
      are reproducible. Second, with the possible exception of the 'quality of social
      interaction' scale, the Japanese version of the KDQOL, can provide
      psychometrically sound kidney-disease-targeted data on quality of life in such
      patients.

PMID- 11508480
TI  - The spatial distribution of horizontal connections in field 18 of the cortex in
      cats.

PMID- 11508482
TI  - Neuron-Glial relationships in various fields of the frontal area of the brain in
      children at different stages of life.

PMID- 11508481
TI  - Characteristics of the development of speech motor areas 44 and 45 in the left
      and right hemispheres of the human brain in early post-natal ontogenesis.

PMID- 11508483
TI  - Morphological analysis of the cluster organization of corticocortical neurons in
      field 17 of the cat visual cortex.

PMID- 11508484
TI  - Structural organization of the area postrema in normal rats and in conditions of
      chronic gravitational overload.

PMID- 11508485
TI  - Descending pathways of the frontal lobe cortex to nuclei of the hypothalamic
      mamillary bodies in craniocerebral trauma in humans.

PMID- 11508486
TI  - The initial stages of the differentiation of pyramidal cells in the deep layers
      of the neocortex in mice during prenatal development.

PMID- 11508487
TI  - The spatial organization of the projections of field 18 into field 17 of the cat
      visual cortex.

PMID- 11508488
TI  - Changes in the ultrastructure of the rat cerebral cortex after oral doses of
      manganese chloride.

PMID- 11508489
TI  - The structure and quantitative characteristics of nuclear and screen-type
      formations of the posterior part of the amygdaloid body.

PMID- 11508490
TI  - The effects of afferent stimulation on neurons in slices of the medial septal
      area and their modulation by biologically active substances in hibernating and
      awake ground squirrels.
AB  - Evoked neuron activity in slices of the medial septal area and its modulation by
      neuropeptides and monoamines was studied in two groups of ground squirrels-
      hibernating and awake animals. Electrical stimulation of the medial forebrain
      bundle evoked predominantly inhibitory effects of different durations. In
      addition, responses were seen consisting of resetting of the phase of background
      volleys to the stimulus after initial inhibition: there were also small numbers
      of short-latency single-spike responses. All the neuropeptides tested. which had
      been identified from the brains of hibernating animals, induced differentiated
      reversible effects consisting of modulation of responses; changes in evoked
      activity were seen significantly more often than shifts in spontaneous activity.
      The effects depended on the state of the animal. Thus. peptide TSKYR increased
      the duration of inhibition in hibernating ground squirrels but shortened
      inhibition in awake animals. Peptide TSKY. which had little effect in hibernating
      animals, increased the duration of inhibition in awake animals. Dipeptide DY.
      which decreased the duration of inhibition and increased the amplitude of the
      activatory components of responses in hibernating ground squirrels. had little
      effect in awake animals. The effects of noradrenaline and serotonin correlated to
      a large extent with their effects on spontaneous activity. It is suggested that
      endogenous substances are involved in creating the conditions required for
      increasing the latent excitability and reactivity of septal neurons during
      hibernation. This allows the medial septal area to function as a "sentry post,"
      allowing the receipt of signals and urgent arousal during hibernation.

PMID- 11508491
TI  - The role of D1-dependent dopaminergic mechanisms of the frontal cortex in delayed
      responding in rats.
AB  - The effects of local microinjections of D1-selective dopaminergic agents into the
      medial wall of the frontal cortex of rats on short-term memory processes were
      studied, along with the effects of proactive interference in immediate and
      delayed spatial choice tasks in a Y maze. Microinjections of the D1 receptor
      antagonist SCH23390 (1 nmol) disturbed performance of both immediate and delayed
      choice tasks. while administration of the D1 receptor agonist SKF38393 (1 nmol)
      had no effect on immediate choice and improved delayed performance. The effects
      of proactive interference, induced by microinjections of SCH23390 and SKF38393
      into the frontal cortex, were significantly more marked in delayed choice than in
      the non-delayed task. Administration of SCH23390 increased the number of
      erroneous excursions made by the animals, the directions of these excursions
      coinciding with the preferred direction of rotation of the animals in a rotation
      test. The results obtained here lead to the conclusion that blockade of
      dopaminergic transmission in the mediofrontal cortex of rats worsens the
      performance of spatial choice in a Y maze by strengthening proactive interference
      processes and disinhibiting the mechanisms which intemally prepare the animals to
      respond to a defined spatial direction with behavioral acts.

PMID- 11508492
TI  - The behavior of ants in a maze in response to a change from food motivation to
      protective motivation.
AB  - The ability of Myrmica rubra scout ants to modify the foraging habit, formed in a
      symmetrical multiple-choice maze, in the situation in which the reinforcement
      (syrup) was replaced with a brood of the same species was studied. When the
      "test" was performed at the same high level of food motivation of the family as
      applied during training, the ants were able successfully to transfer to another
      type of social behavior - transporting of the brood. When the high-level food
      motivation was replaced with a low-level motivation, some of the ants were unable
      to modify the habit. Preliminary utilization in these conditions of reinforcement
      as a switching factor addressing the motivational system for protective behavior
      promoted successful performance of the "test." Criteria allowing identification
      of different methods of modifying behavior during the switch from food motivation
      to protective motivation were developed. A total of 37.5% of the ants transferred
      the strategy formed during training: 40.6% showed gradual remodeling. while 21.9%
      of individuals immediately used the new strategy.

PMID- 11508493
TI  - NMDA glutamate receptor antagonists selectively affect the synaptic mechanisms of
      nociceptive sensitization in snails.
AB  - Defensive behavior command neurons LP11 and RP11 were studied in semi-intact
      snail preparations to investigate the effects of N-methyl-D-aspartate (NMDA)
      receptor antagonists on the mechanisms of nociceptive sensitization. Application
      of sensitizing stimuli to the heads of control snails led to membrane
      depolarization and increased excitability, and also depressed the responses of
      neurons to tactile and chemical sensory stimuli in the short-term stage and
      facilitated responses in the long-term stage of sensitization. Development of
      sensitization in conditions of exposure to the NMDA receptor antagonists AP5 or
      MK-801 produced changes in the membrane potential and membrane excitability of
      command neurons similar to those seen in neurons of control sensitized snails. In
      addition, changes in the responses of command neurons to tactile stimulation of
      the head and foot and chemical stimulation of the foot in these conditions were
      also similar to those seen in neurons of control animals. Acquisition of
      sensitization during administration of NMDA receptor antagonists led to
      pronounced depression of responses to chemical test sensory stimulation of the
      snails' heads in both the short-term and long-term stages of sensitization. Thus.
      in sensitized snails. NMDA glutamate receptor antagonists selectively acted on
      the mechanisms of induction of plasticity the synaptic "inputs" of command
      neurons mediating excitation from chemical sensory stimuli from the animal's
      head.

PMID- 11508494
TI  - A method of operant training to differentiate signals during a delay in providing
      reinforcement in primates.

PMID- 11508495
TI  - The role of interleukin-1 in stress-induced changes in immune system function.
AB  - The cellular-molecular mechanisms of changes in immune system function were
      studied, including the production of lymphocyte activating factor (LAF) and
      interleukin-1 (IL-1). the effects of IL-1 on target cells, and subsequent
      cytokine signal transduction via the sphingomyelin pathway, in different types of
      stress. These experiments showed that stress of different durations and
      intensities induced the formation of lymphocyte activating factors by peritoneal
      macrophages and increased IL-la levels in mouse blood. but led to different
      changes in the responses of target thymocytes to the committing actions of IL
      1beta. which correlated with changes in the level of the humoral immune response.
      These data coincided with differently-directed stress-induced changes in the
      activity of membrane-bound neutral sphingomyelinase. the key enzyme in the
      sphingomyelin cascade, in cerebral cortex membrane fraction P2 from mouse brains.
      The results obtained here suggest that IL-1 is involved in the physiological
      mechanisms of stress reactions, operating at the levels of IL-1 production and
      its biological actions on lymphoid target cells, as well as at the level of
      cytokine signal transduction via the sphingomyelin pathway in nerve tissue.

PMID- 11508496
TI  - The role of neutral sphingomyelinase in interleukin-1beta signal transduction in
      mouse cerebral cortex cells.
AB  - The cytokine interleukin-1 (IL-1) is an important mediator of neuroimmune
      interactions, though it has not been established precisely how the IL-lbeta
      signal is transmitted in nerve cells. This study demonstrates the involvement of
      the sphingomyelin cascade in IL-1beta signal transduction in the P2 membrane
      fraction of the mouse cerebral cortex. The key role of the membrane enzyme
      neutral sphingomyelinase in initiating the sphingomyelin signal transduction
      pathway for this cytokine is supported. The stimulating activity of IL-1beta on
      sphingomyelinase activity in the P2 fraction of the cerebral cortex was found to
      be dose-dependent. Studies using this membrane fraction from mice lacking the IL
      1 type I receptor due to genomic mutations, along with studies using an IL-1
      receptor antagonist. yielded data showing that IL-1beta binding with the type I
      receptor is a necessary event for activation of neutral sphingomyelinase. The
      results obtained here lead to the conclusion that the action of IL-1beta in the
      CNS is mediated by the IL-1 type I receptor and activation of neutral
      sphingomyelinase as the initiating enzyme of the sphingomyelin cascade.

PMID- 11508497
TI  - The effects of hypothyroidism on 5-HT1A and 5-HT2A receptors and the serotonin
      transporter protein in the rat brain.
AB  - The effects of hypothyroidism on 5-HTIA and 5-HT2A receptors and the serotonin
      transporter protein were studied in thyroidectomized male Wistar rats in two
      experimental groups: 1) animals kept on an iodine-free diet hypothyroid rats) and
      2) animals kept on thyroxine (15 microg/kg) for 21 days (giving normal thyroid
      hormone levels. euthyroid animals). Sham-operated rats served as controls.
      Binding of [3H]8-OH-DPAT with 5-HTIA receptors and [3H]citalopram with the
      transporter protein in the hippocampus and midbrain showed no changes in
      hypothyroid rats as compared with controls. Conversely. there were significant
      decreases in [3H]ketanserin binding to 5-HT2A receptors in the frontal cortex in
      hypothyroid rats as compared with controls; this decrease was reversed by
      thyroxine treatment. Thus, losses of cortical 5-HT2A receptors appears to be the
      main consequence of hypothyroidism at the level of the serotonin system of the
      brain.

PMID- 11508498
TI  - Modulation by nitric oxide (NO) of the intensity of non-quantum mediator
      secretion in neuromuscular junctions in rats.
AB  - Experiments on rat diaphragm muscle showed that the nitric oxide (NO) donors
      sodium nitroprusside SNP) and S-nitroso-N-acetylpenicillamine (SNAP). as well as
      L-arginine. a substrate for NO synthesis. decreased the level of muscle fiber
      hyperpolarization (the H effect) after blockade of cholinoceptors on the
      postsynaptic membrane by d-tubocurarine in conditions of irreversible inhibition
      of acetylcholinesterase with armine. Conversely, disruptions to NO synthesis in
      muscle fibers by the NO synthase blocker NG-nitro-L-arginine methyl ester (L
      NAME) led to increases in the H effect both in vitro and in vivo. Inactivated
      solutions of sodium nitroprusside and inactive forms of arginine and NAME (D
      arginine. D-NAME) had no effect on the magnitude of the H effect, while
      hemoglobin, which efficiently binds NO molecules, blocked the inhibitory effects
      of sodium nitroprusside. SNAP, and L-arginine on the magnitude of the H effect.
      All these points provide evidence that NO can function as a modulator of non
      quantum mediator release in the neuromuscular junctions of warm-blooded animals.

PMID- 11508499
TI  - Some blood biochemistry parameters during the cholinergic treatment of
      Alzheimer's disease.
AB  - Acetylcholinesterase (ACE) activity and lipid peroxidation (LPO) parameters were
      measured in the blood of patients with Alzheimer's disease (AD) during treatment
      with amiridine and gliatiline. Treatment was accompanied by inhibition of ACE.
      There was a statistically significant relationship between clinical efficacy and
      changes in ACE activity. AD was charactefized by significant changes in LPO
      parameters, with a three-fold increase in the level of primary oxidation products
      on the background of a sharp (seven-fold) increase in total lipid
      desaturatedness. There was a statistically significant relationship between ACE
      activity and the levels of primary oxidation products in the RBC of patients with
      AD before and after treatment with amiridine and gliatiline.

PMID- 11508500
TI  - The effects of thyroxine isomers on free-radical oxidation processes in
      subcellular fractions of rat cerebral cortex.
AB  - Measurements made by chemiluminescence (CL) were used to estimate effective D-
      and L-thyroxine concentrations and to study their effects on free-radical
      oxidation processes in the mitochondrial and synaptosomal fractions of rat
      cerebral cortex in vitro. These experiments showed that in a model system
      containing riboflavin, the antioxidant activity of D-T4 was 2.2 times greater
      than that of L-T4. The effective concentrations for the two forms of thyroxine
      were I50 = 74.3 +/- 7.1 microM for D-T4 and I50 = 154.7 +/- 12.3 microM for L-T4.
      Studies of the in vitro effects of thyroxine on the membrane fraction of the
      cerebral cortex were based on luminol-dependent peroxide CL. At physiological
      concentrations (10 nM), both isomers of the hormone had identical antioxidant
      activities, which were stronger in the mitochondrial traction, where the
      intensity of CL decreased by 69% and 66%, compared with 45% and 46% decreases in
      the synaptosomal fraction. Since the D-form has no hormonal activity, it is
      suggested that this effect is associated with the phenolic nature of thyroxine.

PMID- 11508501
TI  - Clinical aspects of round window membrane permeability under normal and
      pathological conditions.
AB  - Current research and an overall review of 25 years of round window membrane
      studies are presented. The approach, rationale and concepts that have evolved
      from these studies are described. Ultrastructural studies of the round window
      membrane of humans, monkeys, felines and rodents have disclosed three basic
      layers: an outer epithelium, a middle core of connective tissue and an inner
      epithelium. Interspecies variations are mainly in terms of thickness, being
      thinnest in rodents and thickest in humans. Morphologic evidence suggests that
      the layers of the round window participate in resorption and secretion of
      substances to and from the inner ear, and that the membrane could play a role in
      the defense system of the ear. Different substances, including antibiotics and
      tracers, when placed in the middle ear side traverse the membrane. Tracers placed
      in perilymph become incorporated into the membrane by the inner epithelial cells.
      Permeability is selective and factors affecting permeability include size,
      concentration, electrical charge, thickness of the membrane and tacilitating
      agents. Passage of substances through the membrane is by different pathways, the
      nature of which is seemingly decided at the outer epithelium of the membrane.
      Round window membrane studies have provided increased knowledge of the anatomy
      and function of this structure, as well as new insights into pathology and
      pathogenesis. The concepts that have evolved from these studies are potentially
      useful for understanding middle and inner ear interactions, and for eventual drug
      delivery (based on permeability) to the inner ear.

PMID- 11508502
TI  - The role of neck dissection in the treatment of supraglottic laryngeal cancer.

PMID- 11508503
TI  - Localization of nitric oxide synthase isoforms in the human cochlea.
AB  - The location of nitric oxide (NO) in the structures of the cochlea is a topical
      issue. Nitric oxide synthase (NOS) has been detected previously in mammalian
      cochleae, but information on its presence in the human cochlea is still sparse.
      The location of NOS isoforms I, II and III in substructures of the human cochlea
      was studied by immunohistochemistry (fluorescein isothiocyanate technique) using
      monoclonal antibodies to NOS I, II and III. NOS I was the predominant isoform and
      staining could be observed in cells of the spiral ganglion (SG), in nerve fibres
      and in the outer hair cells (OHC). Furthermore, the supporting cells of the organ
      of Corti and the stria vascularis showed a fluorescent reaction to NOS I.
      Staining for NOS III was less intense and was located in the OHC, supporting
      cells and SG cells, while the stria vascularis remained unstained. By contrast,
      NOS II showed weak staining in a few neuron fibres only. The results imply that
      NO in the human cochlea could act as a neurotransmitter/neuromodulator at the
      level of neural cells and may be involved in the physiology of the supporting
      cells and stria vascularis. Moreover, because NO is both a mediator of
      excitotoxicity and a non-specifically toxic radical, it may also play a role in
      neurotoxicity of the human cochlea.

PMID- 11508504
TI  - Detection of nitric oxide in the guinea pig inner ear, using a combination of
      aldehyde fixative and 4,5-diaminofluorescein diacetate.
AB  - Localization of nitric oxide (NO) production sites in the inner ear of the guinea
      pig was investigated using a combination of glutaraldehyde fixative and a new
      fluorescence NO indicator. 4,5-diaminofluorescein diacetate (DAF-2DA). The
      cochlea and vestibular end organs were examined to locate NO production sites.
      The fluorescence persisted after glutaraldehyde fixation and embedding with water
      soluble resin. NO production in the cochlea was observed in the outer and inner
      hair cells, nerve endings, nerve fibers and supporting cells of the organ of
      Corti, stria vascularis, spiral ligament, ganglion cells, etc. In the vestibular
      end organs, both type I and type II sensory cells, nerve fibers, blood vessels
      and dark cells displayed fluorescence. This localization was exactly identical to
      that of NO synthase. Thus, detection of intracellular NO production by using a
      combination of glutaraldehyde fixation and DAF-2DA is useful for examining the
      function of NO in cells, both in situ and in vivo.

PMID- 11508505
TI  - Laser Doppler measurement of cochlear blood flow changes during conditioning
      noise exposure.
AB  - Using laser Doppler flowmetry, cochlear blood flow was assessed in Mongolian
      gerbils exposed to noise. Anesthetized animals were surgically implanted with
      permanent electrodes and then exposed for 10 consecutive days (6 h on/18 h off)
      to an octave band noise centered at 4 kHz (85 dB SPL). The auditory brainstem
      responses and the blood flow in the basal turn of the cochlea were compared with
      those of gerbils not exposed to noise. The exposed animals developed an initial
      threshold shift, followed by a progressive reduction in threshold shift up to
      complete recovery at the end of the test. In the exposed animals, a reduction in
      the cochlear blood flow during the first 4 days of exposure was observed, which
      was then followed by a progressive increase up to the end of the test. The
      results of this study exclude a possible role of the microvasculature of the
      lateral cochlear wall in determining the resistance to 4 kHz frequency noise
      exposure.

PMID- 11508506
TI  - Dynamics of inner ear pressure change caused by intracranial pressure
      manipulation in the guinea pig.
AB  - Previous studies have shown that pressure changes in the cerebrospinal fluid
      compartment are transmitted to the inner ear. The main route for pressure
      transfer is the cochlear aqueduct. about which little is known with regard to its
      dynamic properties. In the present study, sudden intracranial pressure changes
      (square waves and short pulses) were created in guinea pigs by means of an
      electronically controlled infusion system. Simultaneously with pressure
      manipulation, hydrostatic pressure was monitored in both the peridural space and
      the perilymphatic compartment of the inner ear. The onset of an inner ear
      pressure change following manipulation of intracranial pressure was immediate.
      Inner ear pressure increased or decreased without a measurable time lag, and
      equalized within a few seconds. During square wave intracranial pressure
      manipulation, inner ear pressure equalized somewhat more slowly after pressure
      increase than after pressure decrease. To a first approximation, the pressure
      equalization curves for the inner ear could be fitted with a single exponential
      function, rising or falling with a time constant in the range 1-3 s, and the
      system can be described as a low-pass filter composed of a constant compliance
      and a constant flow resistance. Detailed analysis, however, showed small
      deviations from a purely exponential recovery process. With a more complicated
      (non-linear) model, almost perfect fits to the inner ear pressure equalization
      curves could be obtained. This non-linearity may be a consequence of the
      dependence of the compliance and, or flow resistance on pressure.

PMID- 11508507
TI  - Expression of phospholipase C-gamma1 in experimental cholesteatoma using
      Mongolian gerbils.
AB  - Phospholipase C (PLC)-gamma1 is known to play a central role in ligand-mediated
      signal transduction for cell proliferation. The purpose of this study was to
      elucidate the distribution of PLC-gamma1 in deep meatal skin, retroauricular skin
      and cholesteatoma matrix of experimental animals. We induced canal ligation
      cholesteatoma using Mongolian gerbils and investigated the expression of PLC
      gamma1 in this model by using Western blot analysis and immunohistochemistry. By
      Western blot analysis, considerably higher levels of PLC-gamma1 protein were
      detectable in experimental cholesteatoma. On immunohistochemistry, experimental
      cholesteatoma showed more intense immunolabeling of PLC-gamma1 protein than deep
      meatal skin and retroauricular skin. In conclusion, overexpression of PLC-gamma1
      may in part contribute to abnormal proliferation and differentiation of
      experimental cholesteatoma in Mongolian gerbils.

PMID- 11508508
TI  - Observation of vestibular asymmetry in a majority of patients over 50 years with
      fall-related wrist fractures.
AB  - Previously [The abstract has been shortened somewhat, and the headings removed,
      in order to conform to journal style], we have observed vestibular asymmetry in
      about one-third of healthy senior citizens and in about two-thirds of subjects
      with previous hip fractures and no other significant ailments. Wrist fractures
      are considered a harbinger of hip fractures. If vestibular asymmetry is
      correlated with falls and fractures among the elderly then it should also be
      reflected among subjects with wrist fractures. Sixty-six consecutive patients
      (mean age 67.8 years) who had sustained a fall-related wrist fracture during a 10
      month period were included in the study. The frequency of head shake nystagmus
      among the patients was compared to that found among 49 healthy senior citizens
      (mean age 74.9 years). Nystagmus after head shaking, indicating asymmetric
      vestibular function, was found in 50 participants (76%) (p <0.001). Thirty-eight
      of these were graded with distinct or prominent nystagmus responses. Sixty
      percent of the subjects with horizontal nystagmus had a wrist fracture coinciding
      with the slow phase of nystagmus. Twenty-three subjects reported 30 previous fall
      related fractures during the previous 10 years. Subjects with nystagmus after
      head shaking sustained 26 of these fractures. The frequency of signs of
      vestibular asymmetry was significantly higher (p < 0.001) among the subjects than
      among healthy senior citizens. These findings suggest that an asymmetric
      vestibular function could be an epidemiologically important contributory factor
      to falls and wrist fractures among the elderly population.

PMID- 11508509
TI  - Binaural interaction of bone-conducted auditory brainstem responses.
AB  - Bone-conducted auditory brainstem responses (ABRs) elicited by monoaural
      stimulation are very useful for evaluating hearing in children with congenital
      atresia of both ears. In a previous study of sound lateralization in children
      with congenital atresia of both ears, using bilateral bone-conducted stimuli, we
      found that most of the children could sufficiently retain binaural hearing
      ability in terms of both intensity and time differences. In this study we
      attempted to record bilateral bone-conducted ABRs in normal subjects in order to
      explore binaural interaction objectively. The study revealed that binaural
      interaction exists in bone-conducted ABRs. This can be taken as
      neurophysiological evidence that sound lateralization can be detected by children
      with bilateral microtia and atresia.

PMID- 11508510
TI  - Postoperative vestibular-evoked myogenic potentials in cases with vestibular
      schwannomas.
AB  - Although still the subject of discussion, vestibular-evoked myogenic potentials
      (VEMPs) have been considered to reflect the function of the saccular and, more
      recently, the cochlear tracts. To accurately determine the precise afferent
      pathway carrying VEMPs, we studied the outcomes of VEMPs and other examinations
      in patients with unilateral vestibular schwannomas. Eleven patients with
      unilateral vestibular schwannomas resected using a middle cranial fossa approach
      were included in the study. Patients underwent pure-tone threshold audiometry,
      caloric tests and analysis of auditory brainstem responses (ABRs) and VEMPs pre-
      and postoperatively. The results were compared with those obtained in patients
      with intact superior or inferior vestibular and cochlear nerves. Among the 11
      patients studied, 4 retained their VEMPs postoperatively. Three of the 10
      patients with inferior vestibular schwannomas exhibited normal VEMPs, preserved
      hearing levels (20 dB HL) and anatomically intact superior vestibular nerves. In
      all of these cases, ABRs more closely correlated with VEMPs than with caloric
      responses. In one of the cases with inferior vestibular schwannomas, VEMPs were
      preserved postoperatively and VEMP latencies were shortened, which indicates the
      preoperative presence of a conduction block in either the cochlear or superior
      vestibular nerve. VEMPs may be conducted in both the superior vestibular and
      cochlear nerves, as well as in the inferior vestibular nerve. Thus, evaluation of
      saccular nerve function should be performed carefully, especially in cases where
      hearing is preserved. It appears that cochlear conduction may proceed along two
      pathways, one direct and the other via the brainstem, but this remains to be
      verified.

PMID- 11508511
TI  - Allergic rhinitis does not constitute a risk factor for obstructive sleep apnea
      syndrome.
AB  - Obstructive sleep apnea syndrome (OSAS) is a condition characterized by recurrent
      episodes of obstruction of the upper airway. The aim of this study was to
      evaluate whether nasal obstruction due to allergic rhinitis constitutes a risk
      factor for OSAS. Patients (n = 119) presenting typical symptoms of sleep apnea
      were tested for OSAS using polysomnography. Additionally all patients were tested
      in vivo and in vitro (including nasal eosinophilic cationic protein) for allergic
      rhinitis. Examination for allergic rhinitis revealed that 88.3% of all patients
      had no allergic rhinitis, whereas only 11.7% were diagnosed as allergic. No
      significant differences in sleeping parameters were observed between allergic and
      non-allergic patients. Comparison of parameters indicative of relevant OSAS
      (apnea-hypopnea index [AHI] > 10) revealed that 60% of non-allergic patients had
      relevant OSAS, compared to only 50% of allergic patients. Investigation of
      allergic subgroups revealed similar results: no significant differences in
      sleeping parameters or elevated rates of relevant OSAS parameters were observed,
      especially in perennial allergic rhinitis due to house dust mites. No elevated
      rates of allergic rhinitis were observed in the studied cohort of patients
      suffering from sleep apnea or OSAS. Furthermore, no significant differences in
      sleeping behavior or polysomnography parameters were found on comparing allergic
      and non-allergic patients. In summary, our data rule out allergic rhinitis as a
      major risk factor for OSAS.

PMID- 11508512
TI  - Comparison of six three-dimensional navigation systems during sinus surgery.
AB  - Three-dimensional (3D) navigation systems are routinely used in the fields of
      endoscopic skull base surgery, neurosurgery, maxillo-facial and endoscopic sinus
      surgery. The use of such systems is associated with the following advantages: a
      better 3D orientation: a more confident surgeon; a more precise surgical
      approach; and a reduced operation time. Six different brands of 3D navigation
      system were compared in order to find out if there are major differences in
      performance and whether the considerable financial investment required to
      purchase such a system would be justified by a noticeable improvement in surgical
      interventions and a realization of the above expectations. The 3D navigation
      systems were tested by performing endoscopic sinus surgery on 26 patients
      suffering from chronic sinusitis. The system accuracy, the confidence of the
      surgeon, the time of anaesthesia, the cost, the number of personnel required (and
      their skills), and the technical resources were compared. No major differences in
      performance of the different brands of 3D navigation system were noticed. All of
      the systems showed high, but varying, system precision, the surgeons felt more
      confident and the time of anaesthesia was prolonged by 5-15 min. A well-trained
      operating staff is required. Assuming that the initial costs are excluded and
      that data transfer occurs automatically, personnel costs and the extra time
      required still have to be considered.

PMID- 11508514
TI  - Functional role of nitric oxide in the nasal mucosa of the guinea pig after
      instillation with lipopolysaccharide.
AB  - Nitric oxide (NO) has been found to have various actions in the body. Recently,
      considerable attention has been focused on the intimate relationship between the
      intracellular production of NO and morphological or functional changes in
      ciliated cells. The aim of this study was to clarify the functional significance
      of NO in the nasal mucosa. Healthy, adult, pigmented guinea pigs were randomly
      divided into one control and three experimental groups. The animals were
      instilled with either lipopolysaccharide (LPS) only or LPS plus dexamethasone or
      NG-nitro L-arginine methyl ester (L-NAME). The effect of NO on the nasal
      epithelium was analyzed morphologically by scanning electron microscopy and
      physiologically by ciliary beat frequency (CBF) measurement. The origin of NO was
      also investigated using a fluorescent indicator for NO, namely 4,5
      diaminofluorescein diacetate. LPS induced damage of cilia 3 days after the first
      instillation, while dexamethasone or L-NAME seemed to attenuate the effect of
      LPS. NO production was localized in ciliated cells and the main source of NO in
      ciliated cells is suggested to be inducible NO synthase. The greater number of
      ciliated cells of LPS-treated animals produced a larger amount of NO compared
      with normal animals. LPS also induced a decrease in CBF, which was inhibited by
      dexamethasone or L-NAME. It is suggested that NO may play an important role in
      pathological changes in the nasal mucosa.

PMID- 11508513
TI  - Mometasone furoate nasal spray in the treatment of perennial non-allergic
      rhinitis: a nordic, multicenter, randomized, double-blind, placebo-controlled
      study.
AB  - In order to evaluate the efficacy and safety of mometasone furoate nasal spray
      (MFNS) in patients with perennial non-allergic rhinitis (PNAR) a phase III,
      double-blind, randomized, placebo-controlled, Nordic multicenter study was
      performed at 16 sites (7 in Sweden, 3 in Denmark, 3 in Finland and 3 in Norway).
      A total of 329 patients (age 18-82 years) with a mean duration of PNAR of 9 years
      were included in the study. The total duration of the study was 11 weeks: 2 weeks
      of screening, 6 weeks of treatment and 3 weeks of follow-up. Inclusion criteria
      were unspecific rhinitis symptoms and exclusion criteria were a positive skin
      prick test as well as intolerance to aspirin or non-steroidal anti-inflammatory
      drugs. Endoscopy was performed to exclude patients with structural anomalies and
      nasal polyps. The primary efficacy variable was the subject's total overall
      evaluation. In the intention-to-treat (ITT) group of patients (n = 329) the
      improvement rates were 56% (MFNS) and 49% (placebo). In the per-protocol (PP)
      group (n = 251) the corresponding figures were 58% and 47%. Stratifying for
      groups of patients having moderate symptoms, the results were 54% vs 43% in the
      ITT group and 56% vs 41% in the PP group. The therapeutic response showed greater
      improvement in total nasal score as recorded by the investigator in the groups
      treated with MFNS as compared to the placebo group (p = 0.09 [PP], p = 0.14
      [ITT]). Adverse events occurred during the study, upper respiratory tract
      infections and headache being the most frequently reported, but there was no
      statistically significant difference between MFNS and placebo. The results of
      this study indicate that MFNS is a safe and effective treatment for patients with
      PNAR.

PMID- 11508515
TI  - Phagocytosis in the nasopharyngeal secretion by cells from the adenoid.
AB  - The aim of this study was to elucidate whether granulocytes and macrophages in
      surface secretion on the adenoid emanate from the adenoid and whether these cells
      participate in the control of the nasopharyngeal bacterial flora. Samples of the
      adenoid and its surface secretion were obtained during adenoidectomy from 12
      children with recurrent acute otitis media, secretory otitis media or enlarged
      adenoids causing obstruction. Immunochemistry was used to examine the location of
      granulocytes and macrophages in the adenoid as well as the presence of IgA, IgM,
      IgG and plasma cells in the secretion. Phagocytosis in the secretion was examined
      in imprints stained with May Grunwald Giemsa. Acridine Orange and Gram staining
      were used to demonstrate the presence and location of bacteria in the secretion
      and mucosa. As a control, surface secretions were obtained from 12 children
      without any history of recurrent airway problems. Granulocytes and macrophages
      were observed in the epithelium of the adenoid and some of these cells penetrated
      the epithelial surface. Positive staining for IgA, IgM and IgG was observed in
      all secretions. In 10 of 12 children plasma cells were present in the secretion.
      Bacteria were observed in all imprints. With the exception of I child in each
      group phagocytosis of bacteria in the surface secretion was demonstrated from
      imprints in all children. We conclude that granulocytes and macrophages leave the
      adenoid and enter the surface secretion, where constant phagocytic activity takes
      place. The spatial relations between mononuclear and polymorphonuclear cells
      imply a possible cooperation between these cells in the overall control of the
      nasopharyngeal bacterial flora.

PMID- 11508516
TI  - Giant cell reparative granuloma of the temporal bone.
AB  - Giant cell reparative granuloma (GCRG) is an uncommon non-neoplastic lesion that
      typically occurs in the mandible and maxilla: however, its involvement with the
      temporal bone is rare. It is usually misdiagnosed as a giant cell tumor. Although
      regarded as a benign process, GCRG may be locally aggressive. In this paper, we
      describe two cases of GCRG of the temporal bone and review the pertinent
      literature published in English. The clinical course, histological evaluation,
      diagnosis, differential diagnosis, treatment and prognosis of GCRG of the
      temporal bone were investigated.

PMID- 11508517
TI  - A novel technique in the operative treatment of pyriform sinus carcinoma.
AB  - Pyriform sinus carcinoma is a highly malignant carcinoma of the head and neck
      region as a result of its location and its potential for metastatic spread.
      Decisions regarding the operative procedure remain very difficult. In this paper,
      we present a modified partial laryngo-pharyngectomy in which, following extended
      vertical laryngectomy. the cancerous mass is removed from the involved pyriform
      sinus and the remaining hypopharynx is reconstructed by using the preserved outer
      perichondrium of the resected thyroid cartilage. This technique has been applied
      with adequate success during the last five years in five cases in our department.
      It is indicated when a pyriform sinus carcinoma does not extend to the pyriform
      apex and does not involve the anterior and posterior laryngeal commissures,
      paraglottic space, retrocricoid region and posterior pharyngeal wall beyond the
      midline. All patients treated were male and middle-aged. Our technique appears to
      be a reliable alternative for the operative treatment of pyriform sinus
      carcinoma.

PMID- 11508518
TI  - Soluble adhesion molecules and cytokines in tumor-associated tissue eosinophilia
      of nasopharyngeal carcinoma.
AB  - The phenomenon of tumor-associated tissue eosinophilia (TATE) is seen in some
      cases of nasopharyngeal carcinoma (NPC) and is characterized by the eosinophils
      breaking through the vascular wall and pervading the tumor stroma. The
      margination and trans-endothelial migration of eosinophils in a typical
      inflammatory reaction depend on the activating effects of certain cytokines and
      the expression of adhesion molecules on the eosinophils and endothelial cells. In
      order to investigate whether the adhesion molecules and activating cytokines play
      a role in eosinophil tumor infiltration, we measured the serum levels of 3
      adhesion molecules, intercellular adhesion molecule-1, E-selectin and vascular
      cell adhesion molecule-1, and 2 cytokines, IL-3 and IL-5, in 60 NPC patients and
      40 normal healthy subjects. We found that the NPC patients had higher serum
      levels of all three soluble adhesion molecules than the normal subjects but the
      levels of adhesion molecules failed to correlate with the TATE phenomenon. The
      levels of IL-3 and IL-5 appeared not to differ between the NPC and control
      groups. We postulate that the three soluble adhesion molecules do not play a
      major role in TATE and that their elevation in serum may be due to local and/or
      systemic immune responses.

PMID- 11508519
TI  - Idiopathic hypereosinophilic syndrome involving the middle ear: clinical case
      report and discussion.
AB  - Multiple organ system involvement is seen in the idiopathic hypereosinophilic
      syndrome (HES). Cardiovascular, lung and upper airway, liver, spleen, skin and
      nervous systems are frequently involved. In this article, we describe two cases
      of HES involving the middle ear and lung. In both cases, the histological
      pictures showed an increase of eosinophils in the tissue of the tympanic cavity.

PMID- 11508520
TI  - Neural control of force output during maximal and submaximal exercise.
AB  - A common belief in exercise physiology is that fatigue during exercise is caused
      by changes in skeletal muscle metabolism. This 'peripheral' fatigue results
      either from substrate depletion during submaximal exercise or metabolite
      accumulation during maximal exercise in the exercising muscles. However, if
      substrate depletion alone caused fatigue, intracellular ATP levels would decrease
      and lead to rigor and cellular death. Alternatively, metabolite accumulation
      would prevent any increase in exercise intensity near the end of exercise. At
      present, neither of these effects has been shown to occur, which suggests that
      fatigue may be controlled by changes in efferent neural command, generally
      described as 'central' fatigue. In this review, we examine neural efferent
      command mechanisms involved in fatigue, including the concepts of muscle wisdom
      during short term maximal activity, and muscle unit rotation and
      teleoanticipation during submaximal endurance activity. We propose that neural
      strategies exist to maintain muscle reserve, and inhibit exercise activity before
      any irreparable damage to muscles and organs occurs. The finding that symptoms of
      fatigue occur in the nonexercising state in individuals with chronic fatigue
      syndrome indicates that fatigue is probably not a physiological entity, but
      rather a sensory manifestation of these neural regulatory mechanisms.

PMID- 11508521
TI  - Central and peripheral adaptations to physical training in patients with end
      stage renal disease.
AB  - Renal replacement treatment options are life-saving treatments for patients with
      end-stage renal disease (ESRD). However, prolonged survival in patients with ESRD
      is associated with various functional and morphological disorders from almost all
      systems. Anaemia, deconditioning, cardiac dysfunction. impairment of cardiac
      autonomic control and skeletal muscle weakness and fatigue, primarily because of
      'uraemic' myopathy and neuropathy, are the main predisposing factors for their
      poor functional ability. Physical training is being recommended as a
      complementary therapeutic modality. There are generally 3 methods of exercise
      training applied in patients with ESRD: (i) the supervised outpatient programme
      that is held in a rehabilitation centre; (ii) a home exercise rehabilitation
      programme; and (iii) exercise rehabilitation programme during the first hours of
      the haemodialysis treatment in the renal unit. All the available training data
      show that the application of an exercise training programme in patients with ESRD
      enhances their physical fitness. This improvement is due to central and mainly
      peripheral adaptations. Exercise training in these patients increases aerobic
      capacity, causes favourable left ventricular functional adaptations, reduces
      blood pressure in patients with hypertension, modifies other coronary risk
      factors, increases the cardiac vagal activity and suppresses the incidence of
      cardiac arrhythmias. Moreover, exercise training has beneficial effects on muscle
      structural and functional abnormalities. These central and peripheral adaptations
      to exercise training cause an increase in their functional capacity and offer
      them achance of a better quality of life. Moreover, exercise training improves
      exercisee tolerance of renal post-transplant patients.

PMID- 11508522
TI  - The effect of tape, braces and shoes on ankle range of motion.
AB  - Sport injuries are unwanted adverse effects accompanying participation in sports.
      In a wide variety of sports the most common location of injury is the ankle,
      frequently resulting from a forced plantar flexed inversion of the foot exceeding
      the physiological range of motion (ROM). Historically the purpose of external
      support systems is to prevent acute ankle injuries by restricting abnormal ankle
      ROM. It is believed that a superior restrictive effect also implies a superior
      preventive effect. The purpose of this review was to examine the literature
      regarding the restricting effect of adhesive taping, prophylactic ankle
      stabilisers (PAS) and high-top shoes on ankle ROM. It has been found that tape
      restricts ankle eversion and inversion ROM significantly following application.
      However, tape loosens significantly following standardised exercise and sports
      activities. Studies regarding PAS reported that both semi-rigid and nonrigid
      stabilisers give a significant post-application restriction of ankle inversion
      motion. The nonrigid stabilisers show loosening over time during exercise, while
      the semi-rigid stabilisers maintain their restrictive effect over the same time
      span. High-top shoes in comparison to low-top shoes are more effective in
      restricting mechanically imposed ankle inversion ROM. Low-top shoes, however,
      also limit mechanically imposed ankle inversion stress with the ankle in the
      position in which ankle injury occurs most frequently. One must keep in mind,
      however, that a superior mechanical restriction of ankle ROM does not necessarily
      imply a superior preventive effect. Only well-controlled randomised studies can
      show such an effect, and these studies have shown a reduction of ankle injury
      incidence for all 3 prophylactic measures reviewed.

PMID- 11508524
TI  - In-line skating injuries.
AB  - In-line skating has remained a popular recreational activity all over the world.
      The number of injuries seemingly reached a plateau in the late 1990s. However,
      there are still more injuries caused by in-line skating than from skateboarding,
      hockey or lacrosse and rugby. In 1997, the estimated annual cost of medical
      treatment for these injuries in the US was over $US4 billion. Adolescence still
      represents the largest group of skaters, both in participation and injury.
      Although 10- to 14-year-olds account for 60% of injuries, in 1996 the US Consumer
      Product Safety Commission reported nearly 1500 injuries in individuals 65 years
      and over. Risk factors for injury include inexperience, aggressive skating and
      amount of time spent skating. There are also more recent data to suggest that
      self-reported expert skaters are more likely to sustain an injury. Reluctance to
      use personal protective equipment (PPE) by in-line skaters remains high. The
      general consensus is that PPE is effective in reducing the incidence and severity
      of in-line skating injuries. Therefore, efforts should be made to increase
      awareness of risk factors for injury in all skaters; to increase use of safety
      equipment; to provide safe environments for skating; and to legislate skating
      laws that will protect skaters from injuries.

PMID- 11508525
TI  - Extracting aquatic mites from stream substrates: a comparison of three methods.
AB  - Aquatic mites (Hydrachnida, Oribatida, Halacaroidea) are diverse, and can reach
      high densities in the substrates of streams and rivers. Although they are a
      ubiquitous component of these habitats, their small size means that they are
      often overlooked. Using substrate samples from streams in tropical Queensland, I
      compared the thoroughness and time-based efficiency of three methods of
      extraction: sorting live samples without magnification (live-picking); exhaustive
      sorting of preserved samples using a dissecting microscope (microscope-picking);
      and kerosene-flotation of preserved samples followed by sorting with a dissecting
      microscope (kero-float). Live-picked samples yielded significantly fewer
      individuals and species than other methods, and were biased towards larger
      species. Oribatids and halacarids were not found when live-picking was used. Live
      picking and kero-float methods provided similar numbers of mites per minute of
      sampling effort, whereas microscope-picking had a lower efficiency than kero
      float. A combination of live-picking and kerosene-floatation is recommended for
      thorough surveys of stream acarofauna.

PMID- 11508523
TI  - Physiological demands of running during long distance runs and triathlons.
AB  - The aim of this review article is to identify the main metabolic factors which
      have an influence on the energy cost of running (Cr) during prolonged exercise
      runs and triathlons. This article proposes a physiological comparison of these 2
      exercises and the relationship between running economy and performance. Many
      terms are used as the equivalent of 'running economy' such as 'oxygen cost',
      'metabolic cost', 'energy cost of running', and 'oxygen consumption'. It has been
      suggested that these expressions may be defined by the rate of oxygen uptake
      (VO2) at a steady state (i.e. between 60 to 90% of maximal VO2) at a submaximal
      running speed. Endurance events such as triathlon or marathon running are known
      to modify biological constants of athletes and should have an influence on their
      running efficiency. The Cr appears to contribute to the variation found in
      distance running performance among runners of homogeneous level. This has been
      shown to be important in sports performance, especially in events like long
      distance running. In addition, many factors are known or hypothesised to
      influence Cr such as environmental conditions, participant specificity, and
      metabolic modifications (e.g. training status, fatigue). The decrease in running
      economy during a triathlon and/or a marathon could be largely linked to
      physiological factors such as the enhancement of core temperature and a lack of
      fluid balance. Moreover, the increase in circulating free fatty acids and
      glycerol at the end of these long exercise durations bear witness to the decrease
      in Cr values. The combination of these factors alters the Cr during exercise and
      hence could modify the athlete's performance in triathlons or a prolonged run.

PMID- 11508526
TI  - Host plant-mediated interactions between Tetranychus urticae and Eotetranychus
      carpini borealis (Acari: Tetranychidae).
AB  - Competitive interactions between Tetranychus urticae and Eotetranychus carpini
      borealis were investigated under laboratory and greenhouse conditions. When
      placed first to colonize red raspberry leaves, T. urticae caused extinction of E.
      carpini borealis populations. E. carpini borealis had detrimental effects on T.
      urticae but did not cause T. urticae population extinction. The area used by E.
      carpini borealis for egg deposition decreased with an increase in the number of
      T. urticae eggs. Red raspberry showed an induced response to T. urticae and E.
      carpini borealis feeding after two weeks of infestation. Population growth of
      each species was reduced on plants that were previously infested by conspecifics
      but inducible response by one species had no effects on the other species.

PMID- 11508527
TI  - Biological control of strawberry tarsonemid mite Phytonemus pallidus and two
      spotted spider mite Tetranychus urticae on strawberry in the UK using species of
      Neoseiulus (Amblyseius) (Acari: Phytoseiidae).
AB  - Two species of Neoseiulus, N. californicus and N. cucumeris, showed potential for
      biocontrol of phytophagous mites on strawberry. N. californicus controlled
      Tetranychus urticae on potted strawberry plants in a gauze-sided glasshouse at
      temperatures comparable to early summer in the UK (8-20 degrees C). Both species
      of phytoseiid reduced numbers of the tarsonemid Phytonemus pallidus on potted
      strawberry plants under glasshouse conditions (15-23 degrees C). In several
      experiments reductions in the range of 71-81% in numbers of tarsonemid active
      stages and eggs, compared to non-release plants, were obtained. The importance of
      establishing a suitable predator: prey ratio at an early stage was demonstrated
      in an experiment where an initial ratio of 1 N. cucumeris: 10 P. pallidus gave a
      greater degree of control than 1:20 or 1:40.

PMID- 11508528
TI  - Integrated pest management of two-spotted mite Tetranychus urticae on greenhouse
      roses using petroleum spray oil and the predatory mite Phytoseiulus persimilis.
AB  - From 1995 to 1999, four experiments were conducted on greenhouse roses to assess
      the effectiveness of the nC24 petroleum spray oil (PSO), D-C-Tron Plus, against
      two-spotted mite, Tetranychus urticae Koch (Acarina: Tetranychidae), and to
      determine how the oil could be most efficiently and effectively used in
      combination with the predatory mite Phytoseiulus persimilis Athias-Henriot
      (Acarina: Phytoseiidae) in an integrated pest management program. The results
      showed that 0.5% PSO applied fortnightly to roses gave excellent protection from
      T urticae infestation when the mite population was not already established.
      However, PSO applied after roses were infested with T. urticae above the economic
      threshold only stabilised populations without reducing them below that threshold.
      Populations of P. persimilis in the upper and lower canopies were unchanged after
      two sprays of PSO at 7-day intervals, and application of PSO to the upper canopy
      was as effective in controlling T. urticae in the presence of P persimilis as
      spraying the entire plant. Combining PSO with P. persimilis gave better control
      of T. urticae than using P. persimilis alone. The most cost-effective use of PSO
      in the presence of P. persimilis is, therefore, to apply spray only to the upper
      canopy. This will not affect control of powdery mildew with PSO. Comparison of a
      control program for T urticae based on the monitored use of synthetic miticides
      with that based on calendar application of PSO revealed that both gave equally
      effective control. The benefits of combining PSO and P. persimilis in an
      integrated pest management program for T. urticae on roses over a program based
      on synthetic fungicides are discussed.

PMID- 11508529
TI  - Variation in the olfactory response of 13 populations of the predatory mite
      Amblyseius womersleyi to Tetranychus urticae-infested plant volatiles (Acari:
      Phytoseiidae, Tetranychidae).
AB  - We studied the response of the predatory mite Amblyseius womersleyi collected in
      13 different sites in Japan toward Terranychus urticae-infested kidney bean leaf
      volatiles in a Y-tube olfactometer. The predatory mites were collected from eight
      plant species infested by one of three tetranychid mite species. The predators'
      responses to the infested-leaf volatiles varied from 33% to 97% among the
      populations. The predators collected at 10 sites showed a significant preference
      for infested-leaf volatiles, whereas those collected at three tea plantations did
      not distinguish between the infested- and uninfested-leaf volatiles. We discussed
      the possible factors that affected the olfactory response of A. womersleyi
      towards the infested leaf volatiles.

PMID- 11508530
TI  - Emission of volatile organic compounds by apple trees under spider mite attack
      and attraction of predatory mites.
AB  - Emission rates of volatile organic compounds (VOCs) from Pirus malus L. subsp.
      mitis (Wallr.) var. Golden Delicious and var. Starking attacked by the
      phytophagous mite Panonychus ulmi Koch, and their attractiveness to the predatory
      mites Amblyseius andersoni Chant and Amblyseius californicus McGregor, were
      studied during three years. A large variability was found in the emission of
      individual VOCs depending on the infestation, the apple tree variety and the
      date. There were larger total VOC emission rates and larger total VOC leaf
      concentrations in apple trees attacked by phytophagous mites, especially in the
      var. Starking. In infested trees of this variety, there were also more predatory
      mites. An olfactometer assay showed that predatory mites preferentially chose
      branches infested by Panonychus ulmi (85% went to infested branches vs 15% to
      uninfested control branches) indicating that volatiles may be used as cues to
      find their prey.

PMID- 11508531
TI  - Role of Rusa deer Cervus timorensis russa in the cycle of the cattle tick
      Boophilus microplus in New Caledonia.
AB  - Two field experiments were conducted to evaluate the efficiency of Rusa deer in
      the development of the cattle tick Boaphilus microplus in comparison with that of
      steers in the same pastures and under the same conditions of infestation. No
      difference was noted between a mixed steer/deer herd and a pure steer or pure
      deer herd in the infestation pattern of each host, suggesting that attachment to
      the alternative host is mechanical and not affected by the simultaneous presence
      of the primary host on the pasture. Deer are capable of producing engorged viable
      females, with weight and reproductive performances similar to or even better than
      females fed on steers. For moderate levels (1 million larvae per hectare) and
      high levels (32 million larvae per hectare) of pasture infestation, tick burdens
      on steers were not very different (e.g. average 1,911 and 2,681 ticks per m2
      skin, respectively, on day 24). This may be because of saturation of steer skin
      sites at the moderate larval dose. Deer harboured 2.7-33 times fewer ticks than
      steers and produce no engorged females at the moderate larval level and 32 times
      fewer engorged females than steers at the high larval level. Infestation of deer
      was dose-dependent with averages of 12 and 399 ticks per m2 skin on day 25 at the
      moderate and high larval levels, respectively. At a high infestation level of the
      environment, Rusa deer may contribute, but to a limited extent, to infestation of
      pastures and, consequently, of cattle. However, their role in sustaining a viable
      tick population requires further investigation.

PMID- 11508532
TI  - Intractable epilepsy associated with brain tumors in children: surgical modality
      and outcome.
AB  - OBJECTS: The aim of this study was to evaluate the role of surgical modality in
      children with brain tumors and intractable epilepsy. METHODS: Twenty-three
      patients who were treated for brain tumors and intractable epilepsy between
      January 1985 and March 1998 were retrospectively reviewed. The most common tumors
      were dysembryoplastic neuroepithelial tumors (n=9), oligodendrogliomas (n=6), and
      gangliogliomas (n=5). Six patients exhibited cortical dysplasia. The mean
      duration of follow-up was 43.4 months (range 12 to 125 months). Seizure outcome
      was more favorable (Engel's classes I and II) in patients with a complete
      resection of tumor (14/14 vs 6/9 for incomplete resection; P<0.05). There was no
      significant difference in seizure outcome between lesionectomy (n=13) and
      epilepsy surgery (n=10). The likelihood of requiring postoperative antiepileptic
      drugs was not influenced by the extent of resection or type of surgery.
      CONCLUSIONS: On the basis of this study, we conclude that the complete resection
      of these tumors can be an appropriate initial treatment for children with brain
      tumors who experience intractable epilepsy.

PMID- 11508533
TI  - Interleukin-1beta and tumor necrosis factor-alpha in cerebrospinal fluid of
      children with bacterial meningitis.
AB  - Certain cytokines may contribute to the sequence of events that lead to meningeal
      inflammation in bacterial meningitis. The purpose of this study was to determine
      the levels of cytokines in the cerebrospinal fluid (CSF) of children with
      bacterial meningitis and aseptic meningitis of different etiologies. We
      determined the concentrations of interleukin-1beta (IL-1beta) and tumor necrosis
      factor (TNF-alpha) in the CSF of 171 specimens of 144 patients whose cases were
      classified as follow: bacterial meningitis (n=23), aseptic meningitis (n=26) and
      non-meningitis (n=95). The detectable IL-1beta concentration (> or =20 pg/ml) in
      the bacterial meningitis, aseptic meningitis and non-meningitis groups were
      observed with 78.3%, 3.8%, and 8.4%, respectively. Significantly higher serum IL
      1beta concentrations were detected in those with bacterial meningitis than those
      with aseptic meningitis (538.93+/-605.32 pg/ml vs 2.52+/-11.57 pg/ml; P<0.001) or
      among non-meningitis subjects (2.90+/-11.91 pg/ml; P<0.001). The mean TNF-alpha
      concentration was 148.74+/-338.77 pg/ml. There was significantly more TNF-alpha
      than aseptic meningitis (6.85+/-17.93 pg/ml; P<0.001) or non-meningitis (7.67+/
      16.07 pg/ml; P<0.001). With regard to diagnosis, measurement of IL-1beta and TNF
      alpha levels showed sensitivities of 78% and 74%, respectively; specificities of
      96% and 81%, respectively. It is suggested that the levels of these cytokines,
      especially IL-1beta and TNF-alpha, are useful markers for distinguishing
      bacterial meningitis from aseptic meningitis.

PMID- 11508534
TI  - The retrograde ventriculosinus shunt: concept and technique for treatment of
      hydrocephalus by shunting the cerebrospinal fluid to the superior sagittal sinus
      against the direction of blood flow. Preliminary report.
AB  - A retrograde ventriculosinus (RVS) shunt is a watertight connection that delivers
      excess cerebrospinal fluid (CSF) to the superior sagittal sinus (SSS) against the
      direction of blood flow. This method of CSF shunting utilizes the impact pressure
      (IP) of the bloodstream in the SSS to maintain the intraventricular pressure
      (IVP) more than the sinus pressure (SP) regardless of changes in posture or
      intrathoracic pressure (ITP) and discourages stagnation and clotting of blood at
      the venous end of the connection. It also utilizes collapse of the internal
      jugular vein (IJV) in the erect posture to prevent siphonage. During the past 8
      years, 50 RVS shunts were successfully implanted using valveless shunting
      catheters. There were no problems related to incorrect CSF drainage or sinus
      thrombosis. The results indicated arrest of the hydrocephalic process,
      normalization of the IVP and proper shunt function.

PMID- 11508535
TI  - The effect of alignment on the pressure/flow characteristics of flow control
      shunt valves.
AB  - OBJECT: The proper functioning of shunt valves in vivo is dependent on many
      factors, including the valve itself, the antisiphon device (if included), patency
      of inlet and outlet tubing and location of the valve. Two general categories of
      shunt valves are available today, the differential-pressure valve (with or
      without antisiphon device) and the flow-control valve. We have previously shown
      that the relationship between the position of the valve body and the inlet
      catheter tip can have profound effects on the outflow rate of differential
      pressure valves with antigravity devices. The current study was conducted to
      evaluate the importance of this relationship for the pressure/flow
      characteristics of the flow-control shunt valve. METHODS: We bench-tested flow
      control valves from two manufacturers in the system we devised for testing
      differential-pressure valves. Valves were connected to an "infinite" reservoir,
      and the starting head pressure was determined from product inserts. The inlet
      catheter tip was fixed at this position and the valve body was moved in relation
      to the inlet catheter tip. Outflow rates were determined gravimetrically for
      positions +4 to -8 cm relative to the inlet catheter tip. CONCLUSIONS: All flow
      control valves utilized in this study showed nearly constant outflow rate as the
      valve body was moved incrementally with respect to the level of the inlet
      catheter tip. As previously tested, differential-pressure valves exhibit
      significant increases in outflow rate as the valve body is moved below the inlet
      catheter tip. The outflow rate for the flow-control shunt valves does not change
      over the range of effective head pressures used in this study.

PMID- 11508536
TI  - Withdrawal of shunt systems--clinical use of the programmable shunt system and
      its effect on hydrocephalus in children.
AB  - OBJECTS: The most important function of the programmable valve (PV) is to limit
      the shunt-dependent flow of the cerebrospinal fluid by upgrading valve pressure.
      This activates the regular circulation of cerebrospinal fluid, which may make
      successful removal of the shunt possible once sufficient cerebral development has
      been achieved. The purpose of this paper is to indicate the possibility of shunt
      removal using the programmable Medos and Sophy valves (one programmable Sophy
      valve was specially designed for this situation). METHODS: Prior to regular use
      of the PV, removal of existing shunt systems was attempted in 57 children, since
      some systems malfunctioned and others had abdominal tubes that were meanwhile too
      short as the children had grown as they became older. Shunt removal was
      successfully achieved in only 18 patients (32%). However, in patients in whom PV
      valves were used, shunt removal was successful in 68 out of 114 patients (57%).
      This shows that the success rate of shunt removal becomes significantly higher
      when PV valves are used. The 68 cases in which PV valves were used and shunt
      removal was successful were divided into three groups: A, B, and C. In group A
      (36 cases, 53%), the Medos valve was used for the initial PV shunt implantation
      and the pressure was gradually increased up to 200 mmH2O. The shunt systems were
      then withdrawn. Group B (29 cases, 43%) includes patients who experienced both
      the minor symptoms and ventricular enlargement attributable to increased valve
      pressure. The pressure was gradually upgraded by pumping several times and was
      maintained at close to 200 mmH2O. After 6-24 months' observation shunt removal
      was performed, and in 21 out of 29 cases the outcome was good. However, the
      remaining 8 patients (12%) still had symptoms and required shunt reinsertion. The
      specially designed Sophy valves were then used, which allowed the pressure to be
      set at above 200 mmH2O. The pressure was increased by degrees up to 400 mmH2O and
      kept at the same level for 6-24 months. The shunt systems were then removed
      successfully. Although a high pressure setting was required over a sustained
      period, a total of 29 patients (43%) were able to have their shunts removed. In
      group C (3 cases, 4%), which included patients with aqueduct stenosis, the
      pressure was raised and thus allowed ventricle enlargement. Third ventriculostomy
      was performed under neuroendoscopy with the shunt pressure maintained at a high
      level. Shunt systems were removed successfully. CONCLUSIONS: This study showed
      that it is possible to remove the shunt systems in 50% or more of pediatric
      hydrocephalus cases in which PV valves are used. This is achieved through careful
      control of the valve pressure. Close observation is essential during the period
      when the PV pressure is maintained at a high level, as well as 6-12 months after
      shunt removal.

PMID- 11508538
TI  - Outlet fenestration for isolated fourth ventricle with and without an internal
      shunt.
AB  - Conventional shunting of isolated fourth ventricle is notorious for leading to
      frequent and severe complications. We present four patients with isolated fourth
      ventricle who have been treated with open posterior fossa surgery together with
      either outlet fenestration alone or outlet fenestration and a fourth ventricle
      spinal subarachnoid space (SSS) shunt. A survey of the relevant literature did
      not yield any other case reports of fourth ventricle shunting to the SSS under
      such circumstances. This paper discusses the reasons for choosing this mode of
      treatment. The main advantage of this technique is that the catheter is inserted
      along the anatomical long axis of the fourth ventricle. This positioning lessens
      the possibility of irritating or penetrating the brain stem. Moreover, as a more
      physiological solution, the shunt does not require a valve system. Because of
      these advantages, internal fourth ventricle-SSS shunting is proposed as a valid
      alternative to the "classic" fourth ventriculo-peritoneal shunt.

PMID- 11508537
TI  - Association between increased central venous pressure and hydrocephalus in
      children undergoing cardiac catheterization. A prospective study.
AB  - OBJECTS: The relationship between increased central venous pressure (CVP) and
      development of hydrocephalus has been extensively discussed in the neuropediatric
      literature. However, the possibility of a direct connection has not been
      systematically examined. The purpose of this prospective study was to examine
      whether there was a correlation between elevated CVP and hydrocephalus in
      children undergoing cardiac catheterization. METHODS: We used cardiac
      catheterization to measure the right atrial and superior vena caval pressure in
      37 children (mean age 30 months) with congenital heart malformations. The
      children had CVP higher than normal (mean 10.2+/-3.1 mmHg, range 4-18). To
      evaluate the size of the lateral and fourth ventricles, we performed CT scans of
      the brain on each child. Abnormal scans were found in 15/37 children, showing
      brain atrophy (12/37), ventriculomegaly (3/37), and focal infarction (1/37).
      Cerebral atrophy was more likely to occur in young children (P<0.001). The
      average head circumference among these children was less than 2SD below the mean
      for healthy children of comparable ages. Using a correlation coefficient
      regression model, no relationship was found between CVP and ventricular diameters
      or head circumference. CONCLUSIONS: These results argue against the hypothesis
      that mild to moderately elevated venous pressure is involved in the mechanism and
      development of pediatric hydrocephalus.

PMID- 11508539
TI  - Is meningocele really an isolated lesion?
AB  - OBJECT: We designed this study to elucidate the associated occult spinal lesions
      in patients with simple dorsal meningocele. METHODS: The study population was
      comprised of two groups. Group I comprised newly diagnosed patients with dorsal
      spinal meningocele, and group II comprised patients who had had surgery for
      meningocele and presented with progressive neurological deficits. Magnetic
      resonance imaging (MRI) scans of the whole spinal column were done. The
      associated spinal cord malformations were also treated at the same operation.
      There were 14 boys and 8 girls, with an age range from birth to 4 years (mean 3.9
      months), in group I. Of 20 patients (90%) with associated spinal lesions, 6 had
      more than one lesion, excluding hydromyelia. Group II was made up of 6 patients
      who had been previously operated on for a meningocele and who presented with
      tethered cord syndrome. These were 4 boys and 2 girls, who ranged in age from 4
      to 10 years (mean 6 years). RESULTS: The level of the conus terminalis was lower
      than L3 in all patients. The other findings on MRI, besides low conus, were as
      follows: tight filum, split cord malformation, epidermoid, dorsal lipoma and
      hydromyelia. CONCLUSIONS: Meningocele frequently camouflages a second, occult,
      spinal lesion. MRI of the whole spinal column should be performed. An intradural
      exploration performed with a microneurosurgical technique is needed to detect the
      fibrous bands that may lead to spinal cord tethering and to release the entrapped
      nerve roots. The other associated spinal anomalies should be operated on during
      the same operation.

PMID- 11508540
TI  - Cervical dermal sinus associated with dermoid cyst.
AB  - We report a rare case of cervical dermal sinus associated with a dermoid cyst in
      a 10-month-old infant, who presented with a 1-month history of motor weakness of
      the right upper extremity. Magnetic resonance imaging showed an intradural
      extramedullary dermoid cyst extending from C3 to C4, which was connected with the
      skin dimple along the sinus tract. Total excision of the dermoid cyst and the
      sinus tract with C3-5 laminectomy resulted in good functional recovery.

PMID- 11508541
TI  - Tethered cord syndrome preceding syrinx formation--serial radiological
      documentation.
AB  - The authors report a case of tethered cord syndrome preceding the development of
      a syrinx, which subsequently resolved with detethering. This was shown
      conclusively with serial radiological imaging, although the patient did not
      improve clinically. The lack of clinical improvement is likely to be due to the
      delay in surgery caused by infections in this patient, and early detethering
      should therefore be the aim in patients with tethered cord syndrome.

PMID- 11508542
TI  - Sequential MRI in chronic meningitis during adrenocorticotropic hormone treatment
      for West syndrome.
AB  - I report a patient with West syndrome who suffered from chronic meningitis during
      adrenocorticotropic hormone treatment. The pleocytosis of cerebrospinal fluid
      continued, with vacillation, for more than 3 months. Sequential MRI studies with
      gadolinium contrast seem to be essential for evaluation of the activity and
      determination of the treatment in chronic meningitis.

PMID- 11508543
TI  - A case of surgically treated acute cerebellitis with hydrocephalus.
AB  - We report a pediatric case of acute cerebellitis with hydrocephalus requiring
      emergency placement of external ventricular drainage. A 7-year-old boy presented
      with acute development of headache, nausea and vomiting. Magnetic resonance (MR)
      examination revealed obstructive hydrocephalus and marked bilateral cerebellar
      swelling on T2-weighted imaging. After the placement of external ventricular
      drainage, symptoms of intracranial hypertension promptly improved, and other
      clinical and radiological abnormalities gradually resolved following intravenous
      injection of corticosteroids. Surgical treatment and timing in the treatment of
      acute cerebellitis are discussed.

PMID- 11508544
TI  - Award of the Peter Emil Becker Prize 2000 to Prof. Bengt Hagberg, Gothenburg.

PMID- 11508545
TI  - Lessons and indications from three decades of West-Swedish Cerebral Palsy data.

PMID- 11508547
TI  - Acute presentation of childhood adrenoleukodystrophy.
AB  - X-linked adrenoleukodystrophy is a neurodegenerative disorder affecting the
      myelin of the nervous system and the adrenal cortex. The childhood form of the
      disease is typically heralded by subtle neurocognitive changes which later
      progress. Acute presentation of childhood ALD has been reported, but the
      incidence is not known. We reviewed the records of 485 boys with childhood ALD,
      determined those with acute presentation, and classified them as adrenal crisis,
      seizures, or encephalopathy. Of the 485 reviewed cases, 45 (9.3%) presented
      acutely at an average age of 5.5 years. Twenty of 45 (44%) presented with
      seizures, focal seizures in 6 boys and generalized in the remainder with 4 having
      status epilepticus. Twenty out of 45 presented with acute adrenal crisis. Five of
      45 presented with acute encephalopathy or coma. The diagnosis of ALD was rarely
      made in the acute period, but was often suggested by neuroimaging. The accurate,
      rapid diagnosis of ALD has important implications for treatment as well as for
      other family members and should be considered in appropriate patients.

PMID- 11508546
TI  - Hypomyelination and reversible white matter attenuation in 3-phosphoglycerate
      dehydrogenase deficiency.
AB  - White matter abnormalities are a feature of many inborn errors of metabolism and
      magnetic resonance imaging (MRI) of the brain has become an important tool in the
      diagnostic work-up of these disorders. Recently, patients were reported with a
      potentially treatable disorder of serine biosynthesis. They presented with
      congenital microcephaly, severe psychomotor retardation and intractable seizures.
      Low concentrations of the amino acids serine, glycine as well as 5
      methyltetrahydrofolate were found in plasma and CSF and were due to a deficiency
      of the enzyme 3-phosphoglycerate dehydrogenase (3-PGDH). We studied four patients
      aged 10 months to 7 years by MRI before and after treatment with amino acids with
      a follow-up of 16 months to 6 years. Magnetic resonance spectroscopy (MRS) was
      performed in two patients at 4 and 16 months of treatment. Pre-treatment MRI
      demonstrated hypomyelination and profound white matter attenuation in all
      patients. During treatment, a significant increase in white matter volume was
      found and a progress of myelination in two patients. The most striking finding on
      MRS during treatment was an elevated level of white matter choline. Serine
      biosynthesis defects have to be considered in the differential diagnosis of
      patients with mental retardation, microcephaly, seizures, and on MRI
      hypomyelination and white matter attenuation.

PMID- 11508548
TI  - Homocysteine metabolism and effects of folic acid supplementation in patients
      affected with spina bifida.
AB  - Folic acid supplementation around conception decreases the risk of having
      offspring with a neural tube defect. However, the aetiology is often still
      unknown. This study investigated whether spina bifida patients have lower blood
      folate and higher fasting and post-methionine-load plasma total homocysteine
      (tHcy) concentrations than control patients. Moreover, the effects of
      supplementation with 500 microg folic acid/d on folate and tHcy concentrations
      were determined. Spina bifida patients (n = 12) and disabled control patients (n
      = 15) received 4 weeks of placebo treatment followed by 4 weeks of intervention
      with 500 microg folic acid/d. Blood was collected at the start and after 4 and 8
      weeks. A methionine-loading test was performed at the start and the end of the
      study. At baseline, no significant differences occurred between spina bifida and
      control patients. Folic acid supplementation significantly increased plasma and
      red blood cell folate concentrations in both groups. Folic acid decreased fasting
      tHcy concentrations in control patients by 1.6+/-0.5 micromol/l (p<0.01) and in
      spina bifida patients by 2.2 +/- 1.3 micromol/l (p = 0.10). This study does not
      show a derangement in homocysteine metabolism in spina bifida compared to control
      patients. Moreover, folic acid supplementation seems at least as effective in
      spina bifida patients as in controls.

PMID- 11508549
TI  - Atypical and variable clinical presentation of glutaric aciduria type I.
AB  - We report atypical and variable clinical presentation of glutaric aciduria type I
      (GA I) in four children from two Greek families. In one family, a boy with
      typical biochemical and neuroradiological features of GA I suffered a metabolic
      crisis at 16 months of age resulting in a severe movement disorder. His sister,
      two years older and showing identical biochemical features, has remained
      neurologically normal throughout childhood and at six years of age is attending
      normal primary school. Both children are homozygous for P217 L, a novel mis-sense
      mutation in exon 7 of the glutaryl-CoA dehydrogenase (GCDH) gene. In the other
      family, monozygotic twins presented at 6 years of age with mild developmental
      delay and a single episode of hypoglycaemia. Cranial magnetic resonance imaging
      (MRI) scans in both twins revealed almost identical high-signal alterations in
      the periventricular white matter and in the centrum semiovale. Biochemical
      analyses showed massive urinary excretion of glutaric and 3-hydroxyglutaric acids
      and carnitine depletion. Molecular studies showed compound heterozygosity for two
      novel putative null mutations, IVS6-1 G > A and Y413 X, in the GCDH gene. The
      milder clinical course of GA I in three of the four Greek patients demonstrates
      the phenotypic heterogeneity of the disease even within families. Asymptomatic
      siblings of GA I patients should always be investigated, and molecular studies
      may be useful for confirming the diagnosis, particularly when the presentation is
      atypical.

PMID- 11508550
TI  - Successful trial of amantadine hydrochloride for two patients with alternating
      hemiplegia of childhood.
AB  - We report here the efficacy of amantadine hydrochloride for two patients with
      alternating hemiplegia of childhood (AHC) that did not respond to flunarizine.
      Amantadine was administered to one patient at age one year and seven months and
      to the other at age 25 years. The frequencies and duration of the hemiplegic
      attacks significantly improved in both patients. However, the attacks gradually
      returned to the previous level after a significant reduction in seizures for
      three years in the younger patient with ongoing AHC. Our therapeutic results
      further support the hypothesis that glutamate and NMDA receptors are involved in
      inducing alternating hemiplegic attacks, because amantadine as well as its
      derivative, memantine, are clinically available non-competitive N-methyl-D
      aspartate (NMDA) receptor antagonists, with neuroprotective effects. Amantadine
      is worth trying when treating patients with AHC as a first trial or a substitute
      for flunarizine once the latter agent looses effect.

PMID- 11508551
TI  - Congenital bilateral perisylvian syndrome (CBPS): do concomitant esophageal
      malformations indicate a poor prognosis?
AB  - Congenital bilateral perisylvian syndrome (CBPS) is a syndrome of cortical
      malformation characterized by faciopharyngoglossomasticatory diplegia. We report
      on two cases of CBPS with associated esophageal malformations and a poor mental
      and motor development. The association of CBPS and esophageal malformations may
      indicate a subgroup of patients with a very early prenatal injury, characterised
      by a bad prognosis due to severe cortical disorganization. However, it can not be
      excluded that the association of CBPS and esophageal malformation is purely
      coincidental.

PMID- 11508552
TI  - Hydrocephalus internus in two patients with 5,10-methylenetetrahydrofolate
      reductase deficiency.
AB  - Hydrocephalus internus (HCI) of all four ventricles in association with early
      neurological abnormalities is described as the presenting symptom in two patients
      with 5,10-methylenetetrahydrofolate reductase (MTHFR) deficiency. Decreased
      activity of MTHFR leads to reduction of 5-methyltetrahydrofolate, the main methyl
      donor for methionine synthesis necessary for synthesis of S-adenosyl-methionine
      (SAM). Demyelination in MTHFR deficiency has been attributed to low SAM levels in
      the brain. The biochemical hallmarks of the disorder are hyperhomocystinemia,
      homocystinuria and low levels of plasma methionine. Hydrocephalus internus
      requiring neurosurgical intervention has to our knowledge not been reported as a
      presenting feature of homocystinuria due to deficiency of MTHFR so far. The
      surprising finding of HCI of all four ventricles in MTHFR deficiency must be kept
      in mind when evaluating patients with hydrocephalus of unknown origin.

PMID- 11508553
TI  - Recurrent alternating facial paralysis and malignant hypertension.
AB  - A previously healthy 11-year old girl with three episodes of alternating facial
      palsy is described. On examination during the third relapse a severe essential
      hypertension was diagnosed, accompanied by abnormalities on cerebral imaging,
      cardiac and fundoscopic investigations. Antihypertensive treatment normalized the
      hypertension. No relapse of the facial palsy occurred since. The objective of
      this communication is to draw the attention to hypertension as a possible cause
      of recurrent facial paralysis in children, to stress the importance of measuring
      the blood pressure and taking a thorough family history in every patient
      presenting with facial palsy.

PMID- 11508554
TI  - Presence of delayed myelination and macrocephaly in the sister of a patient with
      vacuolating leukoencephalopathy with subcortical cysts.
AB  - Leukoencephalopathy with swelling and a discrepantly mild clinical course ("van
      der Knaap disease") is a recently identified syndrome. It is characterised by
      macrocephaly occurring during the first year of life, initially normal or nearly
      normal development, and slowly progressive ataxia and spasticity with initial
      preservation of intellectual functions. MRI shows diffuse abnormality in signal
      intensity, as well as swelling of the hemispheral white matter with subcortical
      cyst-like spaces in the fronto-parietal and anterior temporal areas. It is
      thought to have an autosomal recessive mode of inheritance, since many patients
      have consanguineous parents and more than one affected patient is often present
      within the same family. We report on two sibs: a 5-year old boy affected with
      "van der Knaap disease" and his macrocephalic sister whose first MRI (2 years 6
      months) showed delayed myelination, which led us to suspect the same disease as
      her brother, however with subsequent normalisation at the second MRI (3 years 6
      months).

PMID- 11508555
TI  - Arthrogryposis multiplex congenita and pituitary ectopia. A case report.
AB  - We report a patient with a form of arthrogryposis multiplex congenita who
      developed seizures at 4 months of age that proved to be hypoglycemic. Further
      evaluation of the etiology of hypoglycemia led to the discovery of partial
      anterior hypopituitarism, with normal posterior pituitary function. Neuroimaging
      revealed an ectopic neurohypophysis with very small anterior pituitary, the
      presumed anatomic basis for his endocrine dysfunction. A chance association
      between the pituitary ectopia and the arthrogryposis cannot be ruled out.
      However, it is more likely that in the present patient a common genetic mechanism
      may be the basis for both the arthrogryposis and the pituitary dysfunction.

PMID- 11508556
TI  - Idiopathic neuralgic amyotrophy in children. A distinct phenotype compared to the
      adult form.
AB  - Two cases of neuralgic amyotrophy (idiopathic brachial plexus neuropathy) in
      children are presented and combined with a review of the literature. Difficulties
      in establishing the diagnosis are illustrated, and we give an overview of the
      phenotype of childhood neuralgic amyotrophy and its distinctions from the adult
      type. Pain, in adult cases present in over 95% of the cases, is less frequent in
      children, and its absence by no means excludes the diagnosis. In children under 8
      weeks of age, the literature shows that a subsequent osteomyelitis of the
      shoulder or arm always seems to be involved, which warrants a close follow-up.
      Overall, recovery is less favourable in children, but when they fully recover
      they seem to do so in a shorter period of time than adults. We conclude that
      neuralgic amyotrophy in children is distinct from the adult variety, and that it
      has a definite place in the differential diagnosis of a sudden limp arm, even if
      it is painless.

PMID- 11508557
TI  - Secondary non-response due to development of neutralising antibodies to botulinum
      toxin A during treatment of children with cerebral palsy.

PMID- 11508558
TI  - An examination of methods for risk-adjustment of rehospitalization rates.
AB  - This study examines three methods of conducting risk-adjustment to determine if
      the choice of method results in different conclusions about comparative mental
      health center performance. The three methods of risk-adjustment are
      stratification-weighting, logistic regression without interaction effects, and
      logistic regression with interaction effects. The dependent variable of interest
      is psychiatric rehospitalization within 14-60 days of discharge to a community
      mental health center. Subjects are adults discharged in fiscal year 1998 from
      inpatient psychiatric care to a designated community mental health center in
      Oklahoma. Using each method, we examine the mental health centers to determine
      whether their rehospitalization rates are significantly greater than, less than,
      or not different from, expected. Results show that, for some agencies, method of
      risk adjustment leads to different conclusions about center performance. Results
      are discussed with respect to identifying the preferred method of risk
      adjustment, study limitations, and next steps in developing risk-adjustment
      technology and applications.

PMID- 11508559
TI  - Establishing a new research agenda for studying psychiatric emergency room
      treatment decisions.
AB  - With the growing complexity of treatment decisions made at presentation to a
      psychiatric emergency room (PER) and the increasing influence of managed care on
      the decision-making process, it is increasingly important to establish a new and
      more sophisticated research agenda for studying PER decision making. The main
      goal of this paper is to propose a comprehensive conceptual model of the PER
      decision-making process that will facilitate active pursuit of such a research
      agenda. The proposed model presents both traditional and emerging elements of the
      PER decision-making process (i.e., determinants, mediating mechanisms, and
      outcomes) and explicates the nature of the relationships among them at different
      levels of analysis. The model's theoretical and empirical implications for future
      research are discussed and suggestions are made as to the research designs and
      methods needed to pursue this agenda.

PMID- 11508560
TI  - Social patterns of substance use among people with dual diagnoses.
AB  - An ethnography, part of the larger New Hampshire Dual Diagnosis Study, discovered
      in a small subsample (n = 16) that clients participated in 1 (or sometimes 2) of
      4 distinct and different social patterns of substance-use. These 4 patterns, (1)
      "the lone user," (2) "the small, closed social clique," (3) "the large, open user
      syndicate," and (4) the "entrepreneurial drug provider," manifest important
      social functions of such substance-use. These social functions need to be taken
      into account as case managers attempt to persuade clients to abstain from using
      substances, because changing one's substance-use immediately affects one's
      participation in these user networks. Case managers can understand the social
      pressures toward certain patterns of substance-use by attending to the social
      patterning of that use. Many social functions provided by these social patterns
      must be continued by other means if clients, once persuaded to attempt
      abstinence, are to be effectively supported in their sobriety.

PMID- 11508561
TI  - Outcomes associated with clinical profiles of children in psychiatric crisis
      enrolled in intensive, in-home interventions.
AB  - Little is known about the characteristics of children and youth presenting at
      emergency settings in psychiatric crisis, and virtually nothing is known about
      their outcomes. The purpose of this study is to describe the clinical profiles of
      238 children presenting at two psychiatric emergency settings and enrolled in a
      randomized controlled trial of three intensive in-home interventions. A second
      purpose is to examine child mental health outcomes, based on clinical profile and
      to suggest the utility of using a clinical-profiles approach.

PMID- 11508562
TI  - Cost-effectiveness of an HIV prevention intervention for mentally ill adults.
AB  - Adults with severe mental illness are at high risk for human immunodeficiency
      virus (HIV) infection and transmission. Small-group interventions that focus on
      sexual communication, condom use skills, and motivation to practice safer sex
      have been shown to be effective at helping mentally ill persons reduce their risk
      for HIV. However, the cost-effectiveness of these interventions has not been
      established. We evaluated the cost-effectiveness of a 9-session small-group
      intervention for women with mental illness recruited from community mental health
      clinics in Milwaukee, Wisconsin. We used standard techniques of cost-utility
      analysis to determine the cost per quality-adjusted life year (QALY) saved by the
      intervention. This analysis indicated that the intervention cost $679 per person,
      and over $136,000 per QALY saved. When the analysis was restricted to the subset
      of women who reported having engaged in vaginal or anal intercourse in the 3
      months prior to the baseline assessment, the cost per QALY saved dropped to
      approximately $71,000. These estimates suggest that this intervention is
      marginally cost-effective in comparison with other health promotion
      interventions, especially if high-risk, sexual-active women are preferentially
      recruited.

PMID- 11508563
TI  - Traumatic symptomatology in children who witness marital violence.
AB  - For many years, research has demonstrated the devastating effects of violence
      upon children, particularly in the form of direct physical and sexual abuse. What
      has only recently come to into focus are the potential effects of witnessing
      violence upon children. This area of vicarious victimization seems of particular
      import given the fact that so many youngsters are known to witness violent acts
      within their own households. This paper shall review the psychological effects
      which may be effected upon children as a result of witnessing marital violence.
      Relevant research issues concerning the potential roles of moderating and
      mediating variables will also be discussed.

PMID- 11508564
TI  - Child and adolescent mental health emergency services in Eastern European former
      Iron Curtain countries.
AB  - This paper describes the evolution of child and adolescent mental health
      emergency services in Eastern European countries over the past decade since the
      dissolution of the Iron Curtain. The process of helping countries to organize
      services, as facilitated by the authors through their training and mentoring of
      Eastern European mental health professionals, organized by the Children's Mental
      Health Alliance Foundation, with funding from the Soros Foundation, is described.
      This paper is a prelude to reports from six Eastern European countries which
      describe in more detail how child and adolescent mental health emergencies are
      evaluated and treated locally.

PMID- 11508565
TI  - Child and adolescent mental health emergency services in Lithuania.
AB  - This paper describes the development of emergency mental health services for
      children and adolescents in Lithuania over the past decade. The dramatic changes
      in child and adolescent psychiatry which correspond to the move away from the
      Soviet school to democracy and the restoration of the independent Lithuanian
      state are outlined. The paper includes: the nature of child mental health
      emergencies in Lithuania, how they are evaluated, follow-up care, training and
      supervision, and societal emergencies. Recommendations for the future are made.

PMID- 11508566
TI  - Child and adolescent mental health emergency services in Macedonia.
AB  - This paper describes the development of child and adolescent mental health
      emergency services in Macedonia since 1993. The evolution of services through the
      Mental Crisis Centre for Children and Adolescents, funded by the Open Society
      Institute, and located in six cities is outlined. The paper also defines
      traditional services, the nature of child mental health emergencies, the
      evaluation process, follow-up care and training and supervision. It concludes
      with concern that the mental health emergency system is not sufficient to meet
      the needs of the child and adolescent population, particularly in the face of the
      Kosovar refugee crisis. Recommendations for the future are made.

PMID- 11508567
TI  - Emergency child mental health services in Poland.
AB  - This paper describes emergency child mental health services in Poland. The paper
      defines common emergencies for children and adolescents, describes who responds
      and how services are organized. The evaluation process, interventions and
      treatment follow-up are outlined. The lack of consistency across Poland is
      highlighted. Recommendations for further training of professionals, as well as
      improvements in the mental health and legal systems are made.

PMID- 11508568
TI  - Emergency child mental health services in Estonia.
AB  - This paper describes emergency child mental health services in Estonia. The paper
      defines what is an emergency in Estonia, who provides services to children and
      adolescents, the process of evaluation, follow-up care and societal emergencies.
      Centers for care in Tartu and Tallin are described. The need for ongoing training
      and the expansion of services into the countryside is noted.

PMID- 11508569
TI  - Emergency child mental health services in Latvia.
AB  - This paper describes emergency child mental health services in Latvia. The paper
      defines child mental health emergency and outlines which professionals are
      involved in evaluation and where evaluations occur. The described follow-up
      services are only now developing, with the majority of children still receiving
      minimal mental health services in shelters or detention centers. Recommendations
      for more training of professionals, specific protocols and an integrated system
      of care are made.

PMID- 11508570
TI  - Emergency services in Czech Republic.
AB  - This paper describes emergency mental health services for children and
      adolescents in the Czech Republic. The paper defines need for emergency services,
      describes who provides care, where and how it is provided and follow-up care.
      Training of professionals and societal emergencies are also noted. While a range
      of services exists, increased specialty training for mental health professionals
      is recommended.

PMID- 11508571
TI  - Reactions to adolescent suicide and crisis intervention in three secondary
      schools.
AB  - This study investigated crisis intervention in three secondary schools after the
      suicides of five students, focusing on the 89 classmates' risk of developing
      symptoms of PTSD (measured by IES) and high intensity (HI) grief as measured by
      Hogan Sibling Inventory of Bereavement. Crisis interventions for the students
      varied from none to first talk-throughs and psychological debriefings. Six months
      after the suicide, 30% of the classmates evidenced scores indicative of PTSD and
      9.8% evidenced HI grief. Friendship was a predictor of PTSD and HI grief.
      Inadequate crisis intervention was a risk factor for HI grief. Proper crisis
      intervention, and appropriate screening and focused post-trauma psychotherapy
      after a suicide of a student are recommended.

PMID- 11508572
TI  - Telemedicine in rheumatology.

PMID- 11508573
TI  - Bias in its coat of many colors.

PMID- 11508574
TI  - Imaging damage: scoring versus measuring.

PMID- 11508575
TI  - Linkage and association analysis of candidate genes in rheumatoid arthritis.
AB  - OBJECTIVES: To test for linkage and association to rheumatoid arthritis (RA) in
      multiplex families for polymorphic markers in candidate gene loci. Loci including
      the cytokine cluster on 5q31.1 and IL10, both previously investigated in RA, were
      included along with several other genes including ICAM-1, cMYC, the cytokine
      cluster on 17q11.2 and IL1RA. METHODS: One hundred eighty-five multiplex RA
      families were genotyped for 11 microsatellite markers close to candidate genes.
      Markers showing evidence of linkage and/or association to RA were tested in a
      further cohort of families (n = 99). RESULTS: A single microsatellite marker in
      the GSTM4 gene showed some evidence of linkage, LOD 1.6 (p = 0.006). However,
      there was no evidence of excess allele sharing in the second cohort of families
      tested. There was also evidence of association to RA, using the transmission
      disequilibrium test for a dinucleotide repeat in the IRF gene in the cytokine
      cluster on 5q31.1; this was not replicated in a second cohort of families.
      CONCLUSION: Our results do not provide evidence of a role for these genes in RA
      susceptibility.

PMID- 11508576
TI  - Tumor necrosis factor-alpha (TNF-alpha) converting enzyme contributes to
      production of TNF-alpha in synovial tissues from patients with rheumatoid
      arthritis.
AB  - OBJECTIVE: Expression and function of tumor necrosis factor-alpha (TNF-alpha)
      converting enzyme (TACE) in synovia of patients with rheumatoid arthritis (RA)
      were examined to investigate posttranslational regulation of TNF-alpha production
      by TACE in RA. METHODS: Expression of TACE protein was evaluated by
      immunohistochemistry. Cytokines and soluble cytokine receptors were measured by
      ELISA. TACE mRNA was detected by RT-PCR. The enzymatic activity of TACE was
      measured using TACE-specific fluorogenic substrate. RESULTS: Expression of TACE
      at protein level in synovial tissue (ST) of patients with RA was significantly
      stronger than that of patients with osteoarthritis (OA). In RA, TACE was mainly
      expressed in CD68+ macrophage-like synovial cells. ST from 9 of 9 RA and 3 of 8
      OA patients expressed TACE mRNA. RA ST cells possessed significantly higher TACE
      like enzymatic activity than OA ST. A synthetic TACE inhibitor significantly
      reduced the release of TNF-alpha and p75 TNF receptor from RA ST cells.
      CONCLUSION: TACE is an important regulator of the secretion of TNF-alpha from
      synovia of patients with RA.

PMID- 11508577
TI  - Interferon-gamma enhances interleukin 12 production in rheumatoid synovial cells
      via CD40-CD154 dependent and independent pathways.
AB  - OBJECTIVE: To determine the role of interferon-gamma (IFN-gamma) in CD40-CD154
      dependent production of interleukin 12 (IL-12) by synovial cells of patients with
      rheumatoid arthritis (RA). METHODS: We examined the effects of IFN-gamma, tumor
      necrosis factor-alpha (TNF-alpha), and granulocyte-macrophage colony stimulating
      factor (GM-CSF) on CD40 expression on CD68+ synovial macrophage-lineage cells
      (SMC). The effects of IFN-gamma and soluble CD154 (sCD154) on IL-12 production by
      RA synovial cells were determined by ELISA. RESULTS: CD68+ SMC expressed
      substantial levels of CD40. IFN-gamma, but not TNF-alpha or GM-CSF, markedly
      upregulated CD40 expression on CD68+ SMC. IFN-gamma also dose dependently
      increased IL-12 production by synovial cells. The effects of IFN-gamma on CD40
      expression (EC50 = 127.4 U/ml) were observed at a concentration 19 times lower
      than the effects on IL-12 production (EC50 = 6.8 U/ml). Treatment with IFN-gamma
      at a concentration low enough to augment CD40 expression but not IL-12 production
      enhanced spontaneous IL-12 production synergy with sCD 154. The synergistic
      enhancement of spontaneous IL-12 production was abrogated by CD40-Fc. In
      contrast, IL-12 production induced by high concentration of IFN-gamma was not
      neutralized by CD40-Fc. CONCLUSION: IFN-gamma enhanced IL-12 production via both
      CD40-CD154 dependent and independent pathways in RA synovium. IFN-gamma may play
      a crucial role in the development of RA synovitis through regulation of IL-12
      production.

PMID- 11508578
TI  - Hepatocyte growth factor (HGF), HGF activator, and c-Met in synovial tissues in
      rheumatoid arthritis and osteoarthritis.
AB  - OBJECTIVE: Hepatocyte growth factor (HGF) is a multifunctional polypeptide that
      has been implicated in cancer growth, tissue development, and wound repair. Its
      actions are dependent on activation by HGF activator (HGFA) and its binding to a
      specific HGF receptor (c-Met). We examined the role of HGF, HGFA, and c-Met in
      synovial tissues in rheumatoid arthritis (RA) and osteoarthritis (OA), and their
      localization and mRNA expression. METHODS: Immunohistochemical staining, Western
      blotting, RT-PCR, and in situ hybridization (ISH) for HGF, HGFA, and c-Met were
      performed on synovial tissue specimens from 10 patients with RA and 4 with OA,
      and 2 healthy controls. RESULTS: Immunohistochemical staining revealed that HGFA
      and c-Met were strongly expressed in fibroblasts, macrophages, endothelial cells,
      and synovial lining cells. HGF was expressed only faintly in macrophages and
      fibroblasts, and not at all in the endothelial cells of RA and OA synovial
      tissue. HGFA was detected near 73 and 34 kDa on Western blot analysis,
      corresponding to inactive and active HGFA, respectively. RT-PCR showed HGF, HGFA,
      and c-Met mRNA in RA, OA, and control synovial tissue. ISH and
      immunohistochemistry revealed mRNA expression for HGF, HGFA, and c-Met in the
      cell types mentioned above. CONCLUSION: HGFA, HGF, and c-Met mRNA are expressed
      in synovial tissue in RA and OA, and HGF is activated by HGFA and binds to c-Met
      on endothelial cells, inducing angiogenesis.

PMID- 11508579
TI  - Mature form of interleukin 18 is expressed in rheumatoid arthritis synovial
      tissue and contributes to interferon-gamma production by synovial T cells.
AB  - OBJECTIVE: To investigate the expression and function of interleukin 18 (IL-18)
      in synovial tissue (ST) of patients with rheumatoid arthritis (RA). METHODS: The
      localization of IL-18 in ST was analyzed by immunohistochemistry. IL-18 and IL-18
      receptor (IL-18R) mRNA were detected by RT-PCR. Expression of IL-18 at the
      protein level was analyzed by Western blotting. Cytokines in culture supernatants
      were measured by ELISA. RESULTS: From immunohistochemical analysis, IL-18
      producing cells were localized in the lining layer and sublining region of RA ST.
      Most of them coexpressed CD68 antigen. In ST from patients with osteoarthritis
      (OA), IL-18-producing cells were localized only in the sublining region and the
      numbers of these cells were small. From RT-PCR, RA ST expressed mRNA of IL-18, as
      well as alpha- and beta-chains of IL-18R. OA ST did not express or very weakly
      expressed mRNA of alpha- and beta-chains of IL-18R. ST from RA patients produced
      significantly larger amounts of IL-18 in vitro than OA ST. Western blotting
      revealed that RA ST expressed mature IL-18 more abundantly than OA ST. IL-12
      alone stimulates interferon-gamma (IFN-gamma) production by RA synovial tissue
      cells, but IL-18 alone could not. In the presence of IL-12, however, IL-18 could
      synergistically stimulate IFN-gamma production by RA synovial tissue cells. OA
      synovial tissue cells responded to neither IL-12 nor IL-12 + IL-18. IL-18 showed
      synergistic effects with IL-12 on promoting the ability of synovial T cells from
      RA patients to produce IFN-gamma. CONCLUSION: These findings suggest that mature
      IL-18 is expressed in RA synovia and contributes to the production of IFN-gamma
      by infiltrating T cells.

PMID- 11508580
TI  - Tumor necrosis factor promoter polymorphisms in patients with rheumatoid
      arthritis in Taiwan.
AB  - OBJECTIVE: To investigate the association of tumor necrosis factor (TNF) promoter
      polymorphisms with rheumatoid arthritis (RA) in Taiwan. METHODS: TNF promoter
      polymorphisms at positions -238, -244, -308, -376, -857, and -863 were determined
      in 97 patients with RA and 97 healthy controls using the PCR-RFLP method.
      RESULTS: The phenotypic frequency of TNF-308A was significantly lower in patients
      with RA than in healthy controls. This finding can only be found in HLA-DR4
      negative patients, not in DR4 positive RA patients and controls. The TNF promoter
      polymorphisms at positions -238, -244, -308, -376, -857, and -863 were not
      related to the clinical manifestations of RA patients. CONCLUSION: TNF-308A
      itself or a neighboring gene may be a protective factor for the development of RA
      in the HLA-DR4 negative population in Taiwan. TNF promoter polymorphisms were not
      associated with the clinical manifestations of patients with RA in Taiwan.

PMID- 11508581
TI  - Influence of longterm therapy with methotrexate and low dose corticosteroids on
      type 1 and type 2 cytokine production in CD4+ and CD8+ T lymphocytes of patients
      with rheumatoid arthritis.
AB  - OBJECTIVE: Rheumatoid arthritis (RA) is a chronic inflammatory disease with
      predominance of type I cytokine [interleukin 2 (IL-2), interferon-gamma (IFN
      gamma)] production. In this prospective study, we evaluated the influence of
      longterm therapy with methotrexate (MTX) in combination with low dose
      corticosteroids on the type 1/type 2 cytokine balance in RA. METHODS: Peripheral
      blood mononuclear cells were isolated from 10 controls and 20 patients with RA
      before therapy and after 12 mo of therapy with MTX in combination with low dose
      corticosteroids. Using flow cytometry, the intracellular production of IL-2, IFN
      gamma, and IL-4 was measured in CD4+ and CD8+ T lymphocytes. RESULTS: Compared
      with healthy controls, patients with RA before therapy showed an increased
      percentage of IL-2 positive CD4+ and CD8+ T cells (p = 0.002, p = 0.01,
      respectively). An increased percentage of IFN-gamma positive CD8+ T cells was
      found (p = 0.0006) compared with the control group. After 12 months of therapy, a
      significantly decreased percentage of IL-2 positive CD4+ T cells and IFN-gamma
      positive CD4+ and CD8+ T lymphocytes was observed (p = 0.0003, p = 0.0007, p =
      0.001). The percentage of IL-4/IFN-gamma positive CD4+ and CD8+ T cells was
      significantly higher after 12 months of therapy (p = 0.01, p = 0.02). There was a
      positive correlation between the percentage of IFN-gamma positive CD4+ T cells
      and disease activity variables (Ritchie Index and number of swollen joints) in RA
      patients before therapy (r = 0.6, p = 0.04 and r = 0.4, p = 0.05). CONCLUSION:
      Longterm therapy with MTX in combination with low dose corticosteroids for RA
      influenced the predominance of type 1 cytokines toward normalization of the
      cytokine balance in both CD4+ and CD8+ T lymphocytes.

PMID- 11508582
TI  - Methotrexate inhibits rheumatoid synovitis by inducing apoptosis.
AB  - OBJECTIVE: To clarify the pharmacological action of methotrexate (MTX) on the
      synovium of patients with rheumatoid arthritis (RA) using severe combined
      immunodeficient (SCID) mice in which human RA synovial tissue had been grafted
      (SCID-HuRAg). METHODS: One month after engraftment of human RA tissue into SCID
      mice, MTX (0.3 mg/kg) was administered orally, then the appearance of apoptosis
      in the grafted tissue was examined by TdT mediated dUTP nick end labeling (TUNEL)
      staining and electron microscopy at various time points after MTX administration.
      In cultured synovial cells, synovial apoptotic changes after MTX treatment were
      studied by agarose gel electrophoresis and flow cytometric analysis. To compare
      the histological changes induced by MTX with those induced by other disease
      modifying antirheumatic drugs (DMARD) and a nonsteroidal antiinflammatory drug,
      histological examination of the grafted synovial tissues from SCID-HuRAg mice was
      conducted after 4 weeks of oral administration of MTX (0.3 mg/kg/week),
      salazosulfapyridine (30 mg/kg/day), auranofin (0.2 mg/kg/day), bucillamine (10
      mg/kg/day), or indomethacin (2 mg/kg/day). RESULTS: A significant decrease in the
      number of inflammatory cells was observed in the grafted synovial tissue of MTX
      treated SCID-HuRAg. A similar antiinflammatory effect was not observed with the
      other DMARD. Induction of apoptosis was noted with MTX treatment but not with the
      others. The pro-apoptotic effect of MTX was also observed in synovial cell
      cultures. CONCLUSION: MTX induces apoptosis in RA synovium that, in turn, may
      contribute to its antiinflammatory effect on RA synovitis.

PMID- 11508583
TI  - Influence of sex, age, and menopausal state on the course of early rheumatoid
      arthritis.
AB  - OBJECTIVE: To investigate the influences of the menopausal state, sex, and age on
      the course and outcome of rheumatoid arthritis (RA). METHODS: A cohort of
      patients with early RA (209 female, 123 male) was studied. Sex, age, and
      menopausal state at baseline, and disease activity, radiographic joint
      destruction, and physical disability during 6 years of followup were assessed.
      RESULTS: The Disease Activity Score (DAS) was significantly higher in female
      compared to male patients at any time point except at the time of inclusion. This
      was mainly due to postmenopausal patients. Radiographic joint destruction (RJD)
      was significantly worse in female patients compared to males at the time of
      inclusion. Postmenopausal patients had significantly higher RJD than
      premenopausal patients at the time of inclusion and 3 years thereafter. Older
      male patients showed worse RJD than younger male patients at all time points
      measured. Physical disability was significantly worse in female compared to male
      patients, as well as in postmenopausal compared to premenopausal patients, and
      older male compared to younger male patients. Stepwise regression analysis
      revealed that at 3 years higher age and female sex were the best predictors for a
      worse DAS. Higher age and the interaction term between menopausal state and age
      best predicted higher RJD. Higher age and the interaction term between menopausal
      state and age best predicted Health Assessment Questionnaire (HAQ) score.
      CONCLUSION: Higher age at presentation of RA leads to a more severe disease
      course in terms of DAS, RJD, and HAQ. Although female sex has a deteriorating
      effect on the DAS, the menopausal state is responsible for the major part of the
      differences in outcome between men and women. Postmenopausal state in early RA
      influences future disability and damage, especially in older patients.

PMID- 11508584
TI  - The level of inflammation in rheumatoid arthritis is determined early and remains
      stable over the longterm course of the illness.
AB  - OBJECTIVE: To determine whether the level of inflammatory activity, determined by
      the erythrocyte sedimentation rate (ESR), changes over the longitudinal course of
      rheumatoid arthritis (RA); whether the level of inflammatory activity identified
      early in RA predicts longterm inflammatory status; and whether RA "bums out"
      after many years of inflammatory activity. METHODS: A total of 21,866 consecutive
      ESR determinations from 1,897 patients with RA were analyzed to determine the
      association of inflammatory activity, as estimated by ESR, with duration of
      disease. Data were modeled by generalized estimating equations and random
      selection fractional polynomial regression models, controlling for age, sex, and
      calendar date. RESULTS: In a nonlinear fashion, ESR decreased by 4 mm/h over the
      first 10 years of disease, remained stable over the next 25 years, and increased
      slightly thereafter. Patients treated more recently had lower ESR values.
      Patients with recent onset of RA, when stratified in quartiles of ESR, maintained
      their position over time. CONCLUSION: Although ESR decreases by 4 mm/h over the
      first 10 years of disease, it remains stable or rises thereafter. The course of
      RA, as modeled by the ESR, appears to be "set" early in the disease and good and
      bad prognosis groups can be identified within the first 2 years. There is no
      evidence of general "burned out" RA or a lessening of disease activity with long
      duration of disease. Our findings tend to suggest that the ("usually treated")
      natural history of RA prior to introduction of antitumor necrosis factor agents
      is toward some degree of improvement in the early years. If the newer and
      combination therapies are indeed substantially better than what has been
      available, they must show a shifting of the curve downward, not just in the early
      years where it has occurred historically, but over the entire course of the
      illness.

PMID- 11508585
TI  - Reliability and sensitivity of joint space measurements in hand radiographs using
      computerized image analysis.
AB  - OBJECTIVE: To establish the sensitivity and reliability of proximal
      interphalangeal (PIP) and metacarpophalangeal (MCP) mean joint space measurements
      using standard clinical radiographs of healthy subjects, in order to determine
      the limits at which a change in radiographic joint space could indicate a change
      in actual joint size. METHODS: Repeat hand radiographs of healthy subjects were
      taken using standard techniques at 3-5 day intervals with the hands flat (5
      posteroanterior radiographs in 8 subjects) or in 6 different flexed positions on
      a single occasion (8 subjects). The mean joint space was determined using custom
      soft ware and was validated manually. Measurement reproducibility within
      subjects, within films, and between hand positions was assessed by analysis of
      variance. RESULTS: In repeat radiographs taken in the standard clinical position,
      the precision of individual join space measurements indicates that changes > 0.11
      mm (approximately 7%) would represent an actual physical change in joint space
      width (with 95% probability). Averaging measurements across fingers for a single
      subject decreases the detectable change to 0.05 mm (approximately 3%). With
      increasing flexure, radiographic joint space tended to increase in MCP and
      decrease in PIP. CONCLUSION: Mean finger joint space measured from standard
      clinical radiographs is a reliable and sensitive measurement in healthy subjects
      even with some change in hand position. Work is required to establish whether the
      joint space change measured from serial radiographs of patients with arthritis
      over a period of 6-12 mo exceeds the detectable limits of change derived in this
      study.

PMID- 11508586
TI  - Comparison of extracapsular changes by magnetic resonance imaging in patients
      with rheumatoid arthritis and polymyalgia rheumatica.
AB  - OBJECTIVE: Joint inflammation in polymyalgia rheumatica is regarded primarily as
      a disease of the synovial cavities and bursae, but the adjacent capsules and soft
      tissues have not been evaluated using sensitive imaging methods. We used fat
      suppression magnetic resonance imaging (MRI) to determine anatomical sites of
      inflammatory change in the shoulders of patients with early polymyalgia
      rheumatica (PMR) and a control group of patients with rheumatoid arthritis (RA).
      METHODS: Fourteen patients with PMR and 14 with RA (a total of 20 shoulders in
      each group) were evaluated. T2 SPIR (fat suppressed) coronal oblique MRI
      sequences of the shoulders were performed. Scans were assessed for sites of joint
      effusion, bursitis, tenosynovitis, bone edema, and extracapsular soft tissue
      edema. Statistical analysis was performed using Fisher's test. RESULTS: Nine of
      14 patients (10/20 joints) with PMR but only 2/14 (2/20 joints) with RA had
      prominent edema at extracapsular sites adjacent to the joint capsule or in the
      soft tissues (p = 0.02). Both groups had a comparable degree of joint effusion
      (18 PMR, 17 RA), bursitis (18 PMR, 16 RA), and tenosynovitis (3 PMR, 2 RA).
      CONCLUSION: The only significant difference between the 2 groups was the presence
      of inflammatory change outside the joint cavity in patients with PMR. This may
      contribute to the diffuse nature of symptoms in PMR and have implications for its
      pathogenesis.

PMID- 11508587
TI  - Comparison of disability and quality of life in rheumatoid and psoriatic
      arthritis.
AB  - OBJECTIVE: There is controversy about the severity of peripheral psoriatic
      arthritis (PsA) compared to rheumatoid arthritis (RA). Early reports found PsA to
      be a milder disorder, excepting the mutilans form. Recent reports suggest that
      PsA can be as severe as RA. We compared severity, disability, and quality of life
      in patients with PsA and RA matched primarily for disease duration. METHODS: Data
      relating to the extent and severity of disease were recorded in a hospital clinic
      setting. Recent radiographs of hands and feet were read blinded to diagnosis, and
      information on function and quality of life was collected with the Health
      Assessment Questionnaire (HAQ) and EuroQol-5D, respectively. RESULTS: Forty-seven
      patients were matched for disease duration (median PsA 5 yrs, RA 7 yrs). The
      male/female ratio was 24/23 for PsA, 16/31 for RA, and median ages were 45 and 51
      years, respectively. Patients with RA had significantly more joint involvement of
      metacarpophalangeal joints and wrists, whereas distal interphalangeal joints,
      spine, sternoclavicular joints, and sacroiliac joints were significantly more
      involved in PsA. No difference was found regarding Ritchie Articular Index,
      inflammatory markers, HAQ score, or EuroQol-5D. Patients with RA had
      significantly more damage on radiographs of hands and feet: median (range) Larsen
      score hands PsA 8 (0-91), RA 38 (0-125); feet PsA 4 (0-34), RA 11(0-56). Patients
      with RA were taking significantly more disease modifying drugs. CONCLUSION:
      Peripheral joint damage is significantly greater in RA than in PsA after
      equivalent disease duration, but function and quality of life scores are the same
      for both groups. The additional burden of skin disease in PsA may account for
      this.

PMID- 11508588
TI  - Anti-agalactosyl IgG antibodies in sera from patients with systemic sclerosis.
AB  - OBJECTIVE: To determine the prevalence and clinical correlations of anti
      agalactosyl IgG antibodies (anti-AG IgG) in patients with systemic sclerosis
      (SSc). METHODS: Serum samples from patients with limited cutaneous SSc (lSSc; n =
      49), diffuse cutaneous SSc (dSSc; n = 21), rheumatoid arthritis (RA; n = 10),
      systemic lupus erythematosus (SLE; n = 20), and healthy individuals (n = 20) were
      examined by lectin-enzyme immunoassay using human agalactosyl IgG as antigen.
      RESULTS: Anti-AG IgG were detected in 52 (74%) of 70 patients with SSc, which was
      much higher than the frequency of rheumatoid factor positivity in SSc (16%).
      Levels of anti-agalactosyl IgG antibodies were significantly higher than in
      healthy controls or patients with SLE, but lower than patients with RA. Levels of
      anti-AG IgG in patients with dSSc were significantly higher than in lSSc. SSc
      patients with anti-topoisomerase I antibodies had significantly higher levels of
      anti-AG IgG than SSc patients with anticentromere antibodies. Concerning clinical
      correlation, patients with pulmonary fibrosis showed elevated levels of anti-AG
      IgG compared to those without pulmonary fibrosis. Patients with decreased %VC or
      %DLCO showed increased levels of anti-AG IgG. Elevated levels of anti-AG IgG were
      associated with the presence of contracture of phalanges or cutaneous calcinosis,
      but not the presence of arthritis/arthralgia. CONCLUSION: The results suggest
      that anti-agalactosyl IgG antibody is frequently detected in SSc and is a
      serological indicator for more severe SSc.

PMID- 11508589
TI  - Tight skin mouse subcutaneous hypertrophy can occur in the absence of alphabeta T
      cell receptor-bearing lymphocytes.
AB  - OBJECTIVE: The tight skin (TSK) mouse has been proposed to be a murine model for
      heritable fibrotic disorders, and studies have implicated immune dysregulation in
      TSK pathogenesis. We evaluated the core features of TSK cutaneous pathology to
      ascertain whether cutaneous features were altered in TSK mice deficient in
      alphabeta T cell receptor (TCR)-bearing lymphocytes. METHODS: Blinded qualitative
      evaluations of cutaneous and subcutaneous tissues were performed to determine the
      effect of the TSK mutation and whether the TCR-alpha-/- mutation had any
      influence on TSK mediated pathology. RESULTS: Analysis by light microscopy
      revealed no difference in the thickness or any obvious changes in dermal
      architecture in 2 to 4-month-old TSK mice compared to age and sex matched
      littermate controls. The most consistent feature of TSK dermatohistopathology is
      the substantially expanded superficial fascia with accentuated "lamellar"
      architecture. We found that this reliable pathological marker and the
      characteristic skin tightness were not abrogated when the TSK mutation was
      crossed onto the TCR-alpha-/- background. CONCLUSION: The results dispute
      assertions that cutaneous and subcutaneous sclerosis in the TSK mouse are
      dependent upon the presence of CD4+ cells and that skin tightness can be
      dissociated from these pathological changes.

PMID- 11508590
TI  - High prevalence of thoracic vertebral deformities and discal wedging in
      ankylosing spondylitis patients with hyperkyphosis.
AB  - OBJECTIVE: To study the prevalence of deformities of vertebrae and intervertebral
      discs in patients with ankylosing spondylitis (AS) in relation to fixed
      hyperkyphosis of the spine. METHODS: Altogether 50 patients (15 women, 35 men)
      with AS were studied. Hyperkyphosis was measured by the occiput to wall distance
      (OWD). Anterior (Ha), mid- (Hm), and posterior height (Hp) of the vertebrae and
      intervertebral discs were measured on lateral radiographs of the thoracic (Th5
      Th12) and lumbar spine (L1-L5). Vertebral shapes were analyzed according to
      McCloskey, et al. Wedging of discs was calculated as Ha/Hp. Hyperkyphosis was
      defined as OWD > 1 cm. RESULTS: In the thoracic spine, the prevalence of
      vertebral deformities was higher in patients with hyperkyphosis (n = 38) compared
      to patients without hyperkyphosis (n = 12) (45% vs 8%; p = 0.01). The prevalence
      of thoracic vertebral deformities in patients with hyperkyphosis differed little
      between men and women (39% vs 58%; p > 0.10) and among patients above and below
      the age of 45 years (50% vs 33%; p > 0.10). Patients with one or more deformed
      thoracic vertebrae had a higher mean OWD than patients without deformed vertebrae
      (12 +/- 7 vs 7 +/- 6 cm; p < 0.01). The total sum of deformities of the thoracic
      vertebrae and discs explained 43% of the variance of the age adjusted OWD (p <
      0.001). Deformities of lumbar vertebrae and discs did not contribute to
      hyperkyphosis. CONCLUSION: In patients with AS and hyperkyphosis, deformities of
      the thoracic vertebrae occur frequently and, together with wedging of the
      thoracic discs, contribute significantly to fixed hyperkyphosis of the spine.

PMID- 11508591
TI  - Total hip arthroplasty in ankylosing spondylitis: outcome in 340 patients.
AB  - OBJECTIVE: The longterm outcome of total hip arthroplasty (THA) in ankylosing
      spondylitis (AS) remains unclear. Concern has been expressed regarding joint
      survival, given that recipients are young and active. We present outcome data on
      340 THA after a mean followup of 14 years. METHODS: The 6.7% of patients (n =
      309: 237 contactable) who had undergone THA were identified from our database of
      4569 subjects. Responses were received from 166 subjects (112 men, 54 women, M:F
      = 2:1) who were assessed for employment status and outcome [i.e., pain, mobility,
      satisfaction, disease activity (BASDAI), function (BASFI), and global well being
      (BAS-G)]. A non-THA AS control group was matched for age, sex, and disease
      duration. RESULTS: The mean age at AS disease onset for THA recipients was 19.5
      yrs compared to 24.4 yrs for the total database (p < 0.05). The mean age at the
      first THA was 40.0 yrs. Of the 340 THA, 276 were primary (bilateral in 66%) and
      64 were revisions. The mean followup for THA was 14.0 yrs (range 1-52). Overall,
      for the 340 THA, the patients considered outcome to be very good in 85%. In
      relation to the matched control group, THA patients were comparable for BASDAI,
      but had poorer function (p < 0.05) and lower global well being (p < 0.05). Of the
      80 men under 60 years of age, 39 (49%) were employed compared to 49 (68%) of the
      control group (p < 0.01). Survival of original THA and revisions after 10, 15,
      and 20 yrs was 90%, 78%, 64%, respectively (originals), and 73%, 55%, 55%,
      respectively (revisions). CONCLUSION: The longterm outcome of THA in AS is
      outstanding. THA recipients have a younger age at onset than nonrecipients. The
      longterm survival characteristics of THA in young patients with AS is excellent.

PMID- 11508592
TI  - Association of MICA alleles and HLA-B51 in Italian patients with Behcet's
      disease.
AB  - OBJECTIVE: To evaluate the distribution of the MHC class I chain related gene A
      transmembrane (MICA-TM) alleles in Italian patients with Behcet's disease (BD),
      and to investigate the relative contribution of MICA alleles and HLA-B51 in the
      susceptibility and specific clinical features of BD. METHODS: A total of 69
      consecutive Italian patients who satisfied the International Study Group criteria
      for BD were followed at rheumatology, ophthalmology, and neurology units during a
      3 year period (1997-99). We selected 130 healthy subjects from the same
      geographic areas as controls. All patients and controls were examined for MICA
      microsatellite polymorphisms using polymerase chain reaction. Serological HLA
      class B51 typing was performed by a standard microlymphocytotoxicity technique.
      RESULTS: A strong association with HLA-B51 was observed in patients with BD (OR
      5.7, 95% CI 2.8-11.3). The MICA-TM allele A6, in linkage disequilibrium with HLA
      B51, was only slightly increased in patients compared to controls (60.9% vs
      50.8%; p = NS). No significant associations between HLA-B51 or MICA-TM alleles
      and clinical subgroups, particularly central nervous system or eye involvement,
      were found. CONCLUSION: HLA-B51 is the most important susceptibility gene in BD.
      Association with MICA-A6, when it exists, is secondary to the strong linkage
      disequilibrium with HLA-B51.

PMID- 11508593
TI  - Complications of knee arthroscopy performed by rheumatologists.
AB  - OBJECTIVE: To evaluate the complication rate of knee arthroscopy as performed by
      rheumatologists. METHODS: A prospective study of complication rate in sequential
      patients having knee arthroscopies performed by rheumatologists at University of
      California Los Angeles (UCLA) over an 8 year period. RESULTS: A total of 342 knee
      arthroscopies were performed. There were 6 complications (1.8%), including one
      each of seizure, gout, portal cellulitis, ankle pain, inadequate knee drainage,
      and vasovagal symptoms. There was no longterm morbidity or mortality secondary to
      the procedures. CONCLUSION: Knee arthroscopy performed by experienced
      rheumatologists trained in arthroscopy has a low rate of complications, which are
      mostly minor.

PMID- 11508594
TI  - Chlamydial nucleic acids in synovium in osteoarthritis: what are the
      implications?
AB  - OBJECTIVE: To study whether there is evidence of bacterial DNA in some
      osteoarthritic (OA) joint tissues, and the clinical implications of finding
      bacterial DNA in this relatively noninflammatory disease. METHODS: Polymerase
      chain reaction (PCR) was used to detect DNA of Chlamydia trachomatis, Chlamydia
      pneumoniae, and other bacteria using panbacterial primers in synovial membranes
      and other articular tissues of 32 consecutive patients undergoing surgery for hip
      and knee OA. Patients were interviewed and examined postoperatively. Operative
      reports were reviewed and followup examinations were accomplished on all
      patients. RESULTS: Nine of 32 patients with OA (28.1%) had evidence for bacterial
      DNA in joint tissues with at least one set of primers for Chlamydia: 7 for C.
      trachomatis (21.9%), 2 for C. pneumoniae (6.2%). Five of 32 (15.6%) patients had
      postoperative complications; 3 of these were in patients who showed amplified DNA
      of C. trachomatis in joints and one in a patient in whom we detected Escherichia
      coli. CONCLUSION: C. trachomatis and C. pneumoniae nucleic acids can be present
      in joints in some cases of apparently classical OA. Whether chlamydial or other
      difficult to culture bacterial presence is associated with complications is
      suggested, but remains to be determined. Simple presence of C. trachomatis by PCR
      does not define a clinical syndrome or disease course.

PMID- 11508595
TI  - Bias in uncontrolled therapeutic trials in rheumatology due to selection of
      populations with extreme characteristics.
AB  - OBJECTIVE: To assess the prevalence of biases from selection of patients with
      extreme characteristics in recent uncontrolled therapeutic studies in
      rheumatology. METHODS: We hand searched 4 major rheumatology journals for
      uncontrolled trials published in 1997 or 1998 that measured therapeutic efficacy
      by comparing one or more variables at followup vs at baseline. We evaluated the
      susceptibility to bias from random measurement error and natural variability for
      variables used for defining eligibility that overlap with those used for defining
      outcomes. RESULTS: Twenty-five studies were analyzed. In 22 studies, the
      eligibility criteria were related to the outcome criteria and defined a patient
      population with extreme characteristics. Only 3 studies clearly reported that
      they had performed a baseline measurement separate from the screening
      (eligibility) measurement. The remaining 19 reports (76%) might be susceptible to
      bias: in 7, identical variables were used for eligibility criteria and outcomes;
      3 used outcome variables that were also used for characterizing eligibility along
      with other criteria; 2 used specific eligibility variables that were part of
      composite outcome scores; and 7 selected patients on the basis of vague
      descriptors of disease severity, while disease severity was also the outcome.
      CONCLUSION: Several recent uncontrolled trials of therapeutic interventions in
      rheumatology are subject to biases stemming from the selection of patients with
      extreme characteristics. Baseline evaluations separate from the screening
      measurements should be performed and eligibility criteria and outcomes should be
      carefully defined.

PMID- 11508596
TI  - Previous pain experience in women with fibromyalgia and inflammatory arthritis
      and nonpainful controls.
AB  - OBJECTIVE: To examine the frequency of commonly occurring pain and adverse
      experiences throughout life by self-report in women with fibromyalgia (FM) and
      chronic inflammatory arthritis (IA) and nonpainful healthy women. METHODS: Fifty
      one patients with FM and 44 with IA and 52 nonpainful healthy controls were
      consecutively interviewed in a tertiary clinic setting regarding the occurrence
      of lifetime common pain experience and adverse events, as well as a family
      history of FM and/or a childhood pain environment. RESULTS: Patients with FM
      reported significantly more irritable bowel syndrome, migraine headaches, severe
      menstrual pain, physical and psychological trauma affecting well being, family
      history of FM, and family pain environment than subjects with IA or controls.
      Both patient groups had more adult hospitalizations and surgeries than the
      controls. CONCLUSION: Patients with FM report a high rate of varied pain and
      adverse experiences throughout life. This real or perceived experience of pain
      supports the concept that FM is a lifetime disorder of pain processing.

PMID- 11508597
TI  - Effort testing in patients with fibromyalgia and disability incentives.
AB  - OBJECTIVE: To examine whether symptom exaggeration is a factor in complaints of
      cognitive dysfunction using 2 new validated instruments in patients with
      fibromyalgia (FM). METHODS: Ninety-six patients with FM and 16 patients with
      rheumatoid arthritis (RA) were administered 2 effort or symptom validity tests
      designed to detect exaggerated memory complaints as part of a battery of
      psychological tests and self-report questionnaires. RESULTS: A large percentage
      of patients with FM who were on or seeking disability benefits failed the effort
      tests. Only 2 patients with FM who were working and/or not claiming disability
      benefits and no patient with RA scored below the cutoffs for exaggeration of
      memory difficulties. CONCLUSION: This study illustrates the importance of
      assessing for exaggeration of cognitive symptoms and biased responding in
      patients with FM presenting for disability related evaluations.

PMID- 11508598
TI  - Seasonal symptom severity in patients with rheumatic diseases: a study of 1,424
      patients.
AB  - OBJECTIVE: To examine the nature of seasonal symptoms, their prevalence, and
      differences among rheumatic disorders by examining longitudinal data over a
      period of up to 24 years. METHODS: We used a questionnaire assessment of seasonal
      symptoms using the Seasonal Pattern Assessment Questionnaire (SPAQ) in 1,424
      patients with rheumatoid arthritis (RA), osteoarthritis (OA), and fibromyalgia
      (FM). Clinical status was evaluated with standard assessment measures, and
      reported symptoms were compared with actual seasonal differences measured for
      periods of up to 24 years. RESULTS: About 50% of patients with rheumatic disease
      reported exacerbation of rheumatic symptoms (pain, global severity, and fatigue)
      by seasonal changes. The presence of seasonal symptoms was not related to
      diagnosis or to seasonal affective disorder (SAD) symptoms, and symptoms were
      less common in older patients and in men. The number of symptoms and the severity
      of allied factors (depression, anxiety, pain, global severity, number of months
      with seasonal symptoms) were increased in persons with FM and/or complete SAD
      symptoms. Using circular statistics, the modal months for worse symptoms were
      December and January, and for best symptoms was July. Bimodal patterns of
      seasonality were identified for global severity, joint pain, fatigue, and
      socialization. Seasonal symptoms differed as to the degree at which they were
      dispersed around the 12 month circle. When pain and global severity measurements
      obtained over a 24 year period were analyzed, pain was slightly increased in the
      summer and global severity was not related to season at all. Even when patients
      who specifically reported worse symptoms in winter and best symptoms in summer
      were examined, no effect of season could be found. CONCLUSION: Seasonal rheumatic
      symptoms are commonly reported across all rheumatic diseases, but appear to
      reflect perception rather than reality since reported symptoms do not agree with
      measured clinical scores. In addition, regardless of seasonal complaints,
      measured pain and global severity scores are not worse in winter. Although
      patients with FM and Season (+) patients report more severe symptoms, their
      pattern of reporting and their actual scores do not differ according to season
      compared to persons without FM or positive seasonality.

PMID- 11508599
TI  - An evaluation of telehealth in the provision of rheumatologic consults to a
      remote area.
AB  - OBJECTIVE: To evaluate the feasibility and acceptability of providing telehealth
      consultations in rheumatology. METHODS: A prospective review of new consults from
      a rural area assessed by a rheumatologist in an urban area using telehealth.
      Patient demographics were recorded along with a self-administered questionnaire
      reporting assessment of the acceptability of the process. Referring physician and
      consultant provided open ended feedback as to relative strengths and weaknesses
      of telehealth versus traditional consult. A simple cost and time benefit analysis
      was undertaken. RESULTS: The spectrum of patients with rheumatic disease assessed
      was similar to a traditional consultation clinic. Patients found the overall
      process to be acceptable and effective. Apart from accessibility to specialist
      consultation, the greatest benefit was improved communication among patient,
      referring physician, and consultant. The process was determined to be efficient
      in both time and cost savings. CONCLUSION: Telehealth rheumatology consultations
      are feasible, acceptable, and cost/time effective and are therefore advocated for
      those geographic areas where traditional consultations are not readily available.

PMID- 11508600
TI  - Expression of galectins-1 and -3 correlates with defective mononuclear cell
      apoptosis in patients with juvenile idiopathic arthritis.
AB  - OBJECTIVE: Juvenile idiopathic arthritis (JIA) is characterized by hyperplasia of
      synovial cells and accumulation of mononuclear inflammatory infiltrates, which
      are locally maintained through a balance between cell proliferation and
      apoptosis. Although defective clearance of activated T cells in RA joints has
      been explained by alterations of the Fas-Fas ligand system, this has not been
      confirmed in synovial tissue of patients with JIA. We evaluated the relation
      between expression of galectin-1 (Gal-1) and galectin-3 (Gal-3) (beta-galactoside
      binding proteins with pro- and anti-apoptotic properties, respectively) and the
      apoptosis and proliferation rates of infiltrative lymphocytes in synovial tissue
      of patients with JIA. METHODS: Using slide cytometry and in situ end labeling we
      observed dysregulated apoptosis of infiltrating mononuclear cells within the
      synovial tissue of patients with JIA. RESULTS: Patients with pauciarticular JIA
      showed minimal apoptosis, high Bcl-2 expression, and high or normal proliferation
      rates, while patients with polyarticular disease showed the lowest apoptotic
      indexes, accompanied by low Bcl-2 expression and low proliferation rates. We
      found that Gal-1 expression is downregulated and Gal-3 expression is upregulated
      in synovial tissue from patients with JIA. CONCLUSION: In patients with
      polyarticular JIA, accumulation of inflammatory cells is mainly due to
      downregulated apoptosis, whereas in patients with pauciarticular disease the
      process results from increased proliferation. Defective mononuclear apoptosis in
      synovial inflammatory infiltrates from patients with JIA could be explained in
      part by decreased Gal-1 and increased Gal-3 expression.

PMID- 11508601
TI  - Hemarthrosis as initial presentation of scurvy.
AB  - Vitamin C deficiency or scurvy is a disease now rarely seen except for certain
      populations at risk. When it occurs, diagnosis can be difficult as it can mimic
      other disorders. Its manifestations are primarily due to an abnormality in
      collagen formation causing bleeding in the skin, joints, muscles, or
      gastrointestinal tract and dystrophic hair deformities. We describe a case of
      scurvy in a 43-year-old man who presented with new onset hemarthrosis with no
      history of bleeding disorder. He was found to have perifollicular
      hyperpigmentation and corkscrew hairs, highly suggestive of scurvy. He admitted
      to completely eliminating fruits and vegetables from his diet and his serum
      vitamin C level was markedly decreased. Treatment with daily vitamin C supplement
      led to relief of symptoms and resolution of skin changes.

PMID- 11508602
TI  - Dynamic videomicroscopy evaluation of synovial fluid in gout.

PMID- 11508603
TI  - Cholesterol crystals in gouty bursitis.

PMID- 11508604
TI  - Opioids for osteoarthritis of the hip and knee: which opioids for which patients?

PMID- 11508605
TI  - Clinical improvement in osteoarthritis.

PMID- 11508606
TI  - A multicase family with primary Sjogren's syndrome.

PMID- 11508607
TI  - Catastrophic antiphospholipid syndrome: need for a reappraisal.

PMID- 11508608
TI  - Sigmoid diverticular abscess perforation in 2 patients with rheumatoid arthritis
      treated with high dose corticosteroids. A cautionary tale.

PMID- 11508609
TI  - Rhabdomyolysis and 3,4 methylenedioxymethamphetamine in rheumatological practice.

PMID- 11508610
TI  - The role of colchicine in Helicobacter pylori prevalence and gastric mucosal
      changes in Behcet's disease.

PMID- 11508612
TI  - In vivo quantification of capsular end-point in the nonimpaired glenohumeral
      joint using an instrumented measurement system.
AB  - STUDY DESIGN: Single-group factorial. OBJECTIVES: Quantify glenohumeral joint
      translations as a function of force using an instrumented measurement system. Our
      first specific aim was to compare the magnitude of force (N) required to reach
      capsular end-point between the anterior, posterior, and inferior directions. Our
      second specific aim was to compare the magnitude of translation (mm) at capsular
      end-point between the anterior, posterior, and inferior directions. BACKGROUND:
      Manual force-displacement techniques are subjective in nature, and the clinician
      must rely on "feel" to determine capsular end-point. Several investigators have
      attempted to utilize more objective measures at the glenohumeral joint, however
      none have quantified the force or displacements necessary to achieve a true
      capsular end-point. METHODS AND MEASURES: An arthrometric technique was used to
      measure anterior, posterior, and inferior glenohumeral translations in 20
      nonimpaired shoulders (11 women and 9 men with a mean age of 20.9 +/- 3.6 years).
      RESULTS: The magnitude of applied force required to reach capsular end-point was
      significantly different between directions of translations. Anterior-directed
      translations required a significantly greater magnitude of applied force to reach
      capsular end-point than inferior-directed translations. The magnitude of
      translation was not significantly different between directions at capsular end
      point. CONCLUSIONS: Applied forces in the range of 181 to 203 N are necessary to
      reach capsular end-point in subjects with nonimpaired shoulders. Anterior
      translation required significantly higher forces (203.1 +/- 13.1 N) to reach
      capsular end-point than inferior translation (181.4 +/- 31.9 N).

PMID- 11508611
TI  - Effect of active limb movements on symptoms in patients with low back pain.
AB  - STUDY DESIGN: A descriptive, correlational study of patients with mechanical low
      back pain (LBP). OBJECTIVES: To assess the effect of active limb movements on
      symptoms in patients with LBP and to examine the relationship between symptoms
      with limb movements and select patient characteristics. BACKGROUND: Limb
      movements result in forces applied to the spine and, thus, may be important in
      the examination and treatment of patients with LBP. METHODS AND MEASURES: A total
      of 188 people with LBP, 84 men and 104 women, participated in a standardized
      examination. Six of the items required patients to move their limbs and note LBP
      symptoms as increased, remained the same, or decreased. The prevalence of various
      symptom responses with each limb movement test was calculated. Relationships
      between patient characteristics and reports of increased symptoms were examined
      with Cochran's linear trend statistic and the Spearman and Pearson correlation
      coefficients. Differences in characteristics of patients with and without
      increased symptoms were examined with chi2 test, Mann-Whitney U test, or
      Student's t test for independent groups. RESULTS: An increase in symptoms was
      reported by 149 patients with at least 1 of the limb movement tests, and 3 of the
      patients reported a decrease in symptoms. Across the patient sample, the mean
      number of limb movement tests for which symptoms were reported as increased was
      2.30 +/- 1.64. Patients with an increase in symptoms reported higher average pain
      intensity the week prior to the examination (median = 2; range: 1-5) and higher
      functional disability (mean = 0.25; SD = 0.15) than those without a change in
      symptoms (pain intensity: median = 1; range: 0-2 and functional disability: mean
      = 0.16; SD = 0.12). The correlation between the number of increased symptoms and
      the person's average pain intensity was r = 0.23; the correlation with the
      functional disability score was r = 0.36. Patients with a history of LBP tended
      to report an increase in symptoms with more of the limb movement tests (mean =
      3.5; SD = 1.40) than those without a previous history of LBP (mean = 2.0; SD =
      1.11). CONCLUSIONS: Active limb movements performed during the examination
      primarily resulted in increased LBP symptoms. The presence and number of
      increased symptoms with the active limb movements was related to the patient's
      report of average pain intensity and functional disability. Tests of symptoms
      with active limb movements may provide insight into factors contributing to a LBP
      problem, as well as information to guide the treatment of patients with LBP.

PMID- 11508613
TI  - Reliability of assessing end-feel and pain and resistance sequence in subjects
      with painful shoulders and knees.
AB  - STUDY DESIGN: Descriptive. OBJECTIVES: Examine the intrarater and interrater
      reliability of end-feel and pain/resistance sequence for patients with painful
      shoulders and knees. BACKGROUND: Clinicians make diagnostic and intervention
      decisions based on end-feel and pain/resistance sequence, but few studies have
      examined agreement within and between physical therapists when assessing subjects
      with pathology. METHODS AND MEASURES: Subjects with unilateral knee pain (18 men
      and 22 women with a mean age of 31.8 +/- 9.5 years) or shoulder pain (21 men and
      25 women with a mean age of 34.3 +/- 12.9 years) were examined twice. Two
      physical therapists used standardized positions to evaluate 2 knee motions and 5
      shoulder motions. Evaluators did not interview subjects and were blinded to
      previous test results. Evaluators applied overpressure and noted the end-feel
      while subjects identified the moment their pain was reproduced. Following
      testing, subjects rated their pain intensity. Analyses included: percentage of
      agreement; kappa, weighted kappa, and maximum kappa coefficients; and confidence
      intervals. Analyses were repeated for subjects whose pain intensity during
      testing did not change between examinations. RESULTS: Intrarater kappa
      coefficients varied from 0.65 to 1.00 for end-feel, and intrarater weighted kappa
      coefficients varied from 0.59 to 0.87 for pain/resistance sequence. Most
      coefficients remained stable or improved for the unchanged subjects. Interrater
      kappa coefficients for end-feel and weighted kappa coefficients for
      pain/resistance sequence varied from -0.01 to 0.70. End-feel kappa coefficients
      remained low for the unchanged subjects, but pain/resistance sequence weighted
      kappa coefficients improved. Unbalanced distribution affected many coefficients,
      producing low coefficients even when the percentage of agreement was high.
      CONCLUSIONS: The appropriate use of end-feel and pain/resistance sequence data
      requires reliable data gathering, especially when patients are managed by more
      than one physical therapist. Intrarater reliability of end-feel and
      pain/resistance judgments at the knee and shoulder were generally good,
      especially after accounting for subject change and unbalanced distributions.
      Interrater reliability, however, was generally not acceptable, even after
      accounting for these factors.

PMID- 11508614
TI  - Hip abduction-adduction strength and one-leg hop tests: test-retest reliability
      and relationship to function in elite ice hockey players.
AB  - STUDY DESIGN: Single group, test-retest. OBJECTIVES: To determine: (1) hip
      abduction and adduction torques during concentric and eccentric muscle actions,
      (2) medial and lateral one-leg hop distances, (3) the test-retest reliability of
      these measurements, and (4) the relationship between isokinetic measures of hip
      muscle strength and hop distances in elite ice hockey players. BACKGROUND: The
      skating motion used in ice hockey requires strong contractions of the hip and
      knee musculature. However, baseline scores for hip strength and hop distances,
      their test-retest reliability, and measures of the extent to which these tests
      are related for this population are not available. METHODS AND MEASURES: The
      dominant leg of 27 men (mean age 20 +/- 3 yrs) was tested on 2 occasions. Hip
      abduction and adduction movements were completed at 60 degrees.s(-1) angular
      velocity, with the subject lying on the non-test side and the test leg moving
      vertically in the subject's coronal plane. One-leg hops requiring jumping from
      and landing on the same leg without losing balance were completed in the medial
      and lateral directions. RESULTS: Hip adduction torques were significantly greater
      than abduction torques during both concentric and eccentric muscle actions, while
      no significant difference was observed between medial and lateral hop distances.
      Although hop test scores produced excellent ICCs (> 0.75) when determined using
      scores on 1 occasion, torques needed to be averaged over 2 test occasions to
      reach this level. Correlations between the strength and hop tests ranged from
      slight to low (r = -0.26 to 0.27) and were characterized by wide 95% confidence
      intervals (-0.54 to 0.61). CONCLUSIONS: Isokinetic tests of hip abduction and
      adduction did not provide a strong indication of performance during sideways hop
      tests. Although isokinetic tests can provide a measure of muscular strength under
      specific test conditions, they should not be relied upon as a primary indicator
      of functional abilities or readiness to return to activity.

PMID- 11508615
TI  - Defining core information for the training and continuing education of surgical
      oncologists.

PMID- 11508616
TI  - Isolated limb perfusion in the management of patients with recurrent limb
      melanoma: an important but limited role.

PMID- 11508617
TI  - Continuous leakage measurement during hyperthermic isolated limb perfusion.
AB  - BACKGROUND: Continuous measurement of perfusate leakage into the systemic
      circulation is of the utmost importance and can be performed with the help of
      radioactive tracers. The purpose of this study was to assess changes in the
      perfusion leakage rate between two periods: 1977-1990 and 1991-2000, and to
      determine the factors responsible for these changes. METHODS: During the 1991
      2000 period, 119 patients underwent HILP mainly for locally recurrent melanoma or
      locally advanced soft tissue sarcoma. HILP was performed with melphalan (33%) or
      in combination with TNFalpha (65%). There were 67 iliacal, 12 femoral, 25
      popliteal, and 15 axillary perfusions performed. Leakage into the systemic
      circulation was monitored continuously with the help of 131I-albumin and a
      stationary scintillation detector placed above the heart. RESULTS: The median
      maximum leakage was 2.7% (range 0%-21%) which is significantly less than the
      previous period (1977-1990) where leakage of 8% (range 0%-30%) was reported (P <
      .05). A statistical difference in leakage was detected among perfusion locations
      where the iliac and femoral vessels showed more leakage than the axillary and
      popliteal vessels (P < .05). Furthermore, there appeared to be significantly less
      leakage when TNFalpha was used than when melphalan was the sole drug (P < .05).
      CONCLUSIONS: Nowadays leakage from isolated perfusions into the systemic
      circulation is further minimized compared with the days when melphalan was the
      sole drug used. Increased awareness about TNFalpha leakage, continuous external
      monitoring with 131I-albumin as the main isotope, flow rate regulation in the
      perfusion circuit, and regulation of the patient's systemic blood pressure have
      all been major contributors to this improvement.

PMID- 11508618
TI  - Clinical and cost effectiveness of a new hepatocellular MRI contrast agent,
      mangafodipir trisodium, in the preoperative assessment of liver resectability.
AB  - BACKGROUND: Improved preoperative assessment of focal liver disease and tumors
      could have a potentially significant impact on their treatment. Mangafodipir
      trisodium (Teslascan; Nycomed Amersham Imaging, Little Chalfont, UK) is a new
      hepatocellular contrast agent for use with state-of-the-art MR imaging that, in
      early reports, is accurate in detection and characterization of liver lesions.
      METHODS: Records and diagnostic images of all patients undergoing enhanced
      Teslascan MRI (T-MRI) at our institution were reviewed. We assessed the relative
      sensitivities of contrast-enhanced CT scan (CECT) and T-MRI in detecting lesions,
      as well as the impact of T-MRI in the decision to operate or not on patients. In
      those patients taken to surgery, the correlation between T-MRI and intraoperative
      palpation and intraoperative ultrasound (IOUS) was determined. RESULTS: Fifty
      four patients were noted on CECT to have focal liver lesions and subsequently
      underwent imaging with T-MRI. The T-MRI correlated with CT findings in 22
      patients (41%), upstaged the liver disease in 26, and demonstrated fewer lesions
      in 6. Only 43 patients were considered operative candidates and T-MRI influenced
      the operative decision in 32 patients (74%), dissuading operative intervention in
      14. In the 25 patients without clear preoperative evidence of unresectability who
      were taken to the operating room, T-MRI correlated with findings of
      intraoperative palpation in 19 (76%). In the 20 patients who underwent IOUS, T
      MRI correlated with IOUS in 14 patients (70%). IOUS detected an additional nine
      lesions, all of which were <1 cm. Seventeen patients underwent resection and/or
      ablation of their liver lesions. Compared with pathology, sensitivities of CECT,
      T-MRI, and intraoperative evaluation were 61%, 83%, and 93%, respectively. T-MRI
      failed to predict hepatic-specific unresectability in only one of eight patients,
      the other seven having extrahepatic disease. CONCLUSIONS: These findings suggest
      that T-MRI is more sensitive than CECT in the preoperative predicting of the
      resectability of hepatic lesions. Despite T-MRI accurately correlating with
      intraoperative surgical findings, IOUS should be performed on all patients prior
      to a final decision to resect or ablate a focal liver lesion.

PMID- 11508619
TI  - Patient reluctance toward tamoxifen use for breast cancer primary prevention.
AB  - BACKGROUND: The National Surgical Adjuvant Breast and Bowel Project (NSABP) P-1
      trial demonstrated that tamoxifen reduces the incidence of new breast cancers by
      49% in women at increased risk for breast cancer development. Tamoxifen does have
      side effects, however, including marginally increased risks of endometrial cancer
      and thromboembolic events. In this study, women at increased risk for breast
      cancer development were offered tamoxifen. Their knowledge of tamoxifen as a
      chemopreventive agent was assessed, and factors influencing their acceptance of
      tamoxifen and willingness to take it were determined. METHODS: Forty-three
      patients were identified who qualified to take tamoxifen for primary prevention.
      Patients qualified by having at least a 1.7% 5-year risk of developing breast
      cancer, the criteria for entry into the NSABP P-1 trial. Patients initially
      completed questionnaires designed to assess their knowledge of tamoxifen and its
      associated risks and benefits. Patients were then provided neutral educational
      sessions and literature delineating the actual risks and benefits of tamoxifen.
      Subsequently, patients' decisions regarding taking tamoxifen were reassessed.
      RESULTS: Mean patient age was 52.8 years, with a range of 39 to 74 years. Ten
      patients (23.2%) qualified based on the presence of lobular carcinoma in situ
      (LCIS), seven patients (16.3%) qualified based on increased risk secondary to age
      >60 years, and 26 patients (60.5%) age range 35 to 59 qualified based on risk
      profiles demonstrating significantly increased risk. Of the total 43 patients,
      two (4.7%) elected to start taking tamoxifen. Fifteen patients (34.8%) declined
      immediately, and 26 patients (60.5%) were undecided initially but ultimately
      declined. Educational sessions did not influence patients' decisions. Fear of
      side effects, including endometrial cancer, thromboembolic events, and menopausal
      symptoms, was the most commonly cited reason for declining to take tamoxifen.
      CONCLUSIONS: In this study, the vast majority of patients at increased risk for
      breast cancer perceived that the risks of taking tamoxifen outweighed the
      benefits and declined to take it.

PMID- 11508621
TI  - Highest isotope count does not predict sentinel node positivity in all breast
      cancer patients.
AB  - BACKGROUND: Radioisotope mapping is an essential technical component of sentinel
      lymph node (SLN) biopsy, and most authors define isotope success by an arbitrary
      threshold SLN-to-background ratio. Few studies have examined the degree to which
      the relative level of SLN counts correlates with the presence of metastasis.
      Having removed the SLN with the highest counts, how far should the surgeon
      persist in removing additional SLN which contain much lower levels of isotope?
      METHODS: We performed SLN biopsy, using both radioisotope and blue dye, in 2285
      consecutive patients with stage I-II breast cancer. Successful isotope
      localization was defined as an ex vivo SLN-to-axillary background count ratio of
      at least 4:1, and enhanced pathologic analysis (serial sections and
      immunohistochemistry) was used throughout. RESULTS: Among the 1566 patients with
      more than one SLN site identified, the SLN contained metastasis in 463 (30%). In
      369 (80%) of these SLN-positive cases, the SLN with the highest count contained
      tumor, but in 94 (20%) it was benign. Among these 94: (1) the counts of the
      hottest benign SLN exceeded those of the histologically positive SLN by a ratio
      of at least 10:1 in 31% (29 of 94) of cases, (2) the counts of the positive SLN
      were < 4:1 those of the axillary background in 16% (15 of 94) of cases, and (3)
      blue dye failed to identify 27% of positive SLN. No optimum ratio of SLN-to-SLN
      or SLN-to-background counts identified the positive SLN in all cases. CONCLUSION:
      Although the SLN with the highest counts is positive in 80% of breast cancer
      patients with multiple SLN, neither a relatively high isotope count nor the
      presence of blue dye consistently predict SLN positivity in all breast cancer
      patients. For maximum accuracy, SLN biopsy requires (1) the removal of all nodes
      containing isotope regardless of the relative magnitude of counts, (2) the
      concurrent use of blue dye to salvage those procedures in which isotope fails,
      and (3) the removal of all clinically suspicious non-SLN.

PMID- 11508620
TI  - An outcome study of breast reconstruction: presurgical identification of risk
      factors for complications.
AB  - BACKGROUND: Breast reconstruction following mastectomy has been shown to have a
      salutary effect on the overall psychological well-being of women being treated
      for breast cancer. Unfortunately, however, not every patient is an ideal
      candidate for reconstruction. Complications stemming from reconstructive surgery
      can cause significant morbidity, the most important of which may be the delay of
      subsequent adjuvant antineoplastic therapies, and therefore may not be in the
      best interests of the patient. METHODS: A retrospective study was performed on a
      consecutive series of 123 breast reconstructions in 98 patients, performed by one
      of two plastic surgeons, in a university setting over a 5-year period, for all
      surgical outcomes. Specifically, wound-healing complications, infections, and
      reoperations leading to the potential delay of subsequent chemotherapy or
      radiotherapy were recorded, and possible risk factors leading to these were
      sought. RESULTS: Three presurgical risk factors were found to have a
      statistically significant influence on the development of complications following
      breast reconstruction. These were: (1) increasing obesity, defined by the body
      mass index, (2) an active or recent (<5 year) history of cigarette smoking, and
      (3) a history of previous radiation exposure. Odds ratios were used to describe
      the magnitude of the effect of each factor for the development of complications.
      An ordinal regression analysis was used to create a nomogram based on this
      information that can be used to calculate any individual patient's presurgical
      risk for developing major complications following breast reconstruction, based on
      the presence of these factors. CONCLUSIONS: It is possible, based on the presence
      of specific presurgical risk factors, to predict the probability of developing
      major complications following breast reconstruction. This information can be
      useful to the referring physician and plastic surgeon alike in determining which
      patients are the best candidates for breast reconstruction and which type of
      reconstruction would be best suited for each individual patient.

PMID- 11508622
TI  - Clinical significance and prognostic value of apoptosis related proteins in
      superficial esophageal squamous cell carcinoma.
AB  - BACKGROUND: The purpose of the present study was to examine the expression of
      cell cycle regulators [p53, p21WAF1/CIP1 (p21), and Rb] and apoptosis related
      proteins Bax and Bcl-X(L) and to evaluate the relationship between their
      expressions and clinicopathological findings in patients with superficial
      squamous cell carcinomas of the esophagus. METHODS: We immunohistochemically
      investigated the expression of p53, p21, Rb, Bax, and Bcl-X(L) in 79 patients
      with superficial esophageal carcinoma. RESULTS: p21 overexpression was found in
      mucosal carcinoma (P = 0.05) and a high Bcl-X(L) score was observed for
      submucosal carcinoma (P = 0.03). The patients with high Bcl-X(L) score had more
      frequent lymphatic invasion and lymph node metastasis than did those with low Bcl
      X(L) score (P < 0.05). Univariate analysis revealed significantly shorter
      survival in patients with high Bcl-X(L) expression than in those with low Bcl
      X(L) expression, but Bcl-X(L) expression was not identified as an independent
      prognostic factor by multivariate analysis. CONCLUSIONS: Because Bcl-X(L)
      expression correlated well with depth of tumor invasion, lymphatic invasion, and
      lymph node metastasis, examination of Bcl-X(L) expression will help to estimate
      the properties in superficial squamous cell carcinoma of the esophagus.

PMID- 11508623
TI  - Analysis of early (pT1) gastric cancer with submucosal invasion: surgical
      management and possibility to schedule less invasive surgery.
AB  - BACKGROUND: Early gastric cancer (EGC) is one of the popular targets of less
      invasive surgery. The aim of the present study is to clarify the possibility of
      scheduling a less invasive surgery for EGC cases with submucosal (SM) invasion.
      METHODS: Eighty cases of EGC with SM invasion were analyzed clinicopathologically
      and immunohistochemically. Correlations between factors that reflect cancer
      progression and data from endoscopic examination were investigated. RESULTS:
      Thirteen cases (16.3%) showed lymph node metastasis and the numbers of metastasis
      positive lymph nodes ranged from 1 to 18. Two cases showed lymph node metastasis
      not only in the perigastric area, but also along the left gastric artery and the
      common hepatic artery. Only the tumor size showed a significant correlation with
      lymph node metastasis (P = .014) using the data from preoperative endoscopic
      examination. With respect to p53 overexpression, there was no significant
      correlation with pathologic factors in EGC with SM invasion. The simple
      protuberance types that were <2 cm in diameter had no lymph node metastasis.
      CONCLUSIONS: It seems difficult to predict the progression of EGC with SM
      invasion from the data currently obtained by preoperative endoscopic examination.
      It was suggested that less invasive surgery could be scheduled only for simple
      protuberance type cases that were <2 cm in diameter. Radical gastrectomy and D2
      lymph node dissection is required, in open surgery or laparoscopic surgery, for
      any other type of EGC with SM invasion.

PMID- 11508624
TI  - Adenocarcinoma of the lower third of the rectum surgically treated with a <10-MM
      distal clearance: preliminary results in 35 N0 patients.
AB  - BACKGROUND: Recent reports suggest that a distal clearance (DC) of 10 mm at the
      lower surgical margin may be considered adequate in the surgical treatment of
      rectal cancer, but there are no data on the possible adequacy of a < 10-mm DC in
      N0 patients in whom a good prognosis can otherwise be expected, that is, those
      with negative surgical margins and negative lymph nodes. METHODS: Between
      November 1991 and December 1998, 154 consecutive patients with adenocarcinoma of
      the lower third of the rectum had a total rectal resection with total mesorectal
      excision and coloendoanal anastomosis. Among 76 N0 patients, there were 35 with
      <10-mm DC and 41 with > or =10-mm DC. Each group was divided into two subgroups
      depending on whether the surgical margins were involved or not, and the rate of
      local recurrence in the various categories was compared. All B2 Astler-Coller
      stage patients in the series received postsurgical chemoradiotherapy. RESULTS:
      The local recurrence rate in the 35 patients with DC < 10 mm was 11.4% and that
      of the 41 patients with DC > or =10 mm was 7.3%. When only patients with negative
      surgical margins were considered, the local recurrence rate was 3.4% for those
      with < 10-mm DC and 5.1% for those with > or =10-mm DC. CONCLUSIONS: Our results
      suggest that a radical surgery with <10-mm DC followed by chemoradiotherapy may
      be adequate in N0 patients, provided that a careful pathologic examination of the
      surgical specimen excludes the presence of lymph node metastases and that the
      distal rectal and mesorectal resection margins fall in healthy tissue.

PMID- 11508625
TI  - Zn concentration in thyroid tissue and whole blood of women with different
      diseases of thyroid.
AB  - The Zn concentration in thyroid tissue and whole blood of patients with Graves'
      disease, thyroid cancer, and nodular goiter disease was determined using the
      total-reflection X-ray fluorescence method. The dependence of obtained
      concentrations on the clinical stage of the examined disease, histopathological
      grading, and kind of analyzed material (thyroid tissue and blood) was studied.
      The determined concentration of Zn was the lowest in the thyroid tissue of
      patients with thyroid cancer (23.1 microg/g) and it was the highest in the case
      of Graves' disease (41.7 microg/g), whereas in the blood samples, the reverse
      results were found (7.1 microg/g and 4.8 microg/g, respectively). The physical
      basis of the method used, the experimental setup, and the procedure of sample
      preparation are described.

PMID- 11508626
TI  - Urinary and serum electrolyte changes in athletes during periodic and continuous
      hypokinetic and ambulatory conditions.
AB  - Hypokinesia (HK) (diminished movement) induces significant electrolyte changes,
      but little is known about the effect of periodic hypokinesia (PHK) on minerals.
      The aim of this study was to measure the effect of PHK and continuous hypokinesia
      (CHK) on urinary and serum electrolytes. Studies were done during a 30-d period
      of prehypokinesia (HK) and during 364 d of PHK and CHK periods. Thirty male
      athletes aged 24.6 +/- 7.7 yr were chosen as subjects. They were equally divided
      into three groups: unrestricted ambulatory control subjects (UACS), continuously
      hypokinetic subjects (CHKS), and periodically hypokinetic subjects (PHKS). The
      UACS group experienced no changes in the daily activities and regular training
      and they were maintained under an average running distance of 11.7 km/d. The CHKS
      group was limited to an average walking distance of 0.7 km/d; and the PHKS group
      was limited to an average walking distance of 0.7 and running distance of 11.7
      km/d for 5 d and 2 d/wk, respectively, for a period of 364 d. Urinary and serum
      phosphate (P), calcium (Ca), sodium (Na) and potassium (K), serum intact
      parathyroid hormone (iPTH), calcitonin (CT), plasma renin activity (PRA) and
      aldosterone (PA) levels, food and water intakes, and physical characteristics
      were measured. Urinary P, Ca, Na, and K loss, serum Ca, P, Na, and K, and PRA and
      PA values increased significantly (p < or = 0.01), whereas serum iPTH and CT
      levels decreased significantly (p < or = 0.01) in the PHKS and CHKS groups when
      compared with the UACS group. However, significant (p < or = 0.01) differences
      were observed between PHKS and CHKS groups regarding urinary and serum
      electrolytes, serum and plasma hormones. Food and water intakes, body weight,
      body fat, and peak oxygen uptake decreased significantly (p < or = 0.01) in the
      CHKS group when compared with PHKS and UACS groups. Food and fluid intakes, body
      fat, and body weight increased significantly (p < or = 0.01), whereas peak oxygen
      uptake remained significantly (p < or = 0.01) higher in the PHKS group when
      compared with the CHKS group. Serum and urinary minerals, serum hormones, food
      and fluid intakes, and physical characteristics did not change significantly (p >
      0.01) in the UACS group when compared with their baseline control values. It was
      shown that both PHK and CHK induce significant serum and urinary electrolyte
      changes. However, urinary and serum electrolyte changes were significantly (p <
      or = 0.01) greater during PHK than CHK. It was concluded that the greater the
      stability of muscular activity, the smaller the serum and urinary electrolyte
      changes during prolonged HK.

PMID- 11508627
TI  - Tissue-specific alterations in lipoprotein lipase activity in copper-deficient
      rats.
AB  - Copper deficiency results in alterations in lipid metabolism that include
      elevations in serum cholesterol and triglycerides and a decrease in whole-body
      respiratory quotient. Copper-deficient animals are also leaner even though
      electron micrographs of the myocardium present increased lipid droplet
      accumulation. To address whether a compromised copper status impacts triglyceride
      deposition in a tissue-specific manner, the activity of lipoprotein lipase was
      measured in adipose tissue and cardiac and skeletal muscle. Weanling rats fed a
      copper-restricted diet (<1 ppm) for 6 wk demonstrated a greater than twofold
      increase in cardiac lipoprotein lipase activity concomitant with a significant
      reduction in adipose tissue lipoprotein lipase activity. Skeletal muscle
      lipoprotein lipase activity was not altered by the copper-deficient state. The
      results of this study suggest that copper deficiency may induce a tissue-specific
      alteration in lipoprotein lipase activity in rats, which may contribute to the
      notable deposition of lipid substance in myocardium and the concomitant general
      body leanness.

PMID- 11508628
TI  - Mucosal uptake and whole-body retention of dietary manganese are not altered in
      beta2-microglobulin knockout mice.
AB  - To further examine the interrelationships between manganese and iron absorption,
      the mucosal uptake, initial rate of loss, whole-body retention, and tissue
      distribution of an orally administered 54Mn radiotracer were compared between
      normal and beta2-microglobulin knockout [beta2m(-/-)] mice. These mutant mice are
      commonly used as a model for the study of human hemochromatosis, a hereditary
      iron-overload disease. Initial uptake of 54Mn by the intestinal mucosa, the
      liver, and the brain was not different between the two strains. The mutant mice
      had much higher concentrations of nonheme and total iron in the liver, but
      hepatic manganese, copper, magnesium, and zinc concentrations were similar
      between the two strains. In summary, the mucosal uptake and whole-body retention
      of manganese and tissue manganese concentrations were not altered in beta2m(-/-)
      mice; this suggests that normal homeostasis of manganese is not affected by the
      altered HFE protein-beta2m complex in these mice.

PMID- 11508629
TI  - Trace metals in vertebral columns of deep-sea teleost fish.
AB  - Deep-sea teleost fish were collected from the Sagami Bay near a deep fissure in
      the Pacific Ocean. Fish were identified as Chlorophthalmis albatrosis,
      Engyprosopan xystrias, Satyrichthys hians, Ventrifossa garmani, and Halieutaea
      stellata. The Etmopterus lucifer is not a teleost, but a deep-sea shark. Just
      after being caught and fixed in neutral 20% formol, the vertebral column was
      resected and prepared for measurement by inductively coupled plasma-atomic
      emission spectrometry. Trace elements were found to be Al, Si, Ti, Fe, Cu, Cd,
      Zn, and Hg at micrograms per gram levels. Major elements were Mg, Ca, P, and S at
      the milligram per gram level. Some of trace elements, Zn and Hg, were also
      usually found at this level.

PMID- 11508630
TI  - Selenite or selenomethionine interaction with methylmercury on uptake and
      toxicity showing a weak selenite protection: studies on cultured K-562 cells.
AB  - Selenium and methylmercuric chloride (MMC) interactions regarding cellular uptake
      and selenium protection on MMC toxicity have been studied. Human K-562 cells were
      pretreated or simultaneously treated with either selenite (5 or 50 microM) or
      selenomethionine (10 or 50 microM) together with (3.5 or 5 microM) MMC. Cells
      simultaneously treated with selenite or selenomethionine and 3.5 microM MMC
      showed a decreased mercury concentration with increased selenium dose especially
      seen in the selenite combinations. The simultaneous selenite and MMC 3.5 microM
      combinations showed growth curves with an increasing number of viable cells with
      increased selenite dose. All combinations with 5 microM MMC were toxic to the
      cells. Interactions between selenite or selenomethionine and MMC regarding
      cellular uptake of mercury and selenium were observed and indications of selenite
      protection against MMC toxicity in human K-562 cells were noticed.

PMID- 11508631
TI  - Effect of vanadium compounds on the lipid organization of liposomes and cell
      membranes.
AB  - The influence of vanadate on the adsorption properties of Merocyanine 540 (MC540)
      to UMR cells was studied by means of specrofluorometry. An increment in the
      fluorescence was observed in the osteoblasts incubated with 0.1 mM vanadate. This
      effect could be interpreted in terms of vanadate inhibitory effects on
      aminotraslocase activity. However, vanadate promotes a similar behavior to that
      found in UMR 106 cells when it was added to lipid vesicles composed of
      phosphatidylcholine. The effect of vanadium in different oxidation states, such
      as vanadate(V) and vanadyl(IV) on lipid membrane properties was examined in large
      unilamellar vesicles by means of spectrofluorometry employing different probes.
      Merocyanine 540 and 1,6-diphenylhexatriene were used in order to sense the
      changes at interfacial and hydrophobic core of membranes, respectively. In
      contrast to vanadate, vanadyl decreased the fluorescence of MC540. Both vanadium
      compounds slightly perturbed the hydrocarbon core. The results can be interpreted
      by the specific adsorption of both compounds on the polar head groups of
      phospholipid and suggest a possible influence of vanadium compounds on the lipid
      organization of cell membranes.

PMID- 11508632
TI  - Low-dose zinc administration as an effective Wilson's disease treatment.
AB  - A case of a 11-yr-long Wilson's disease treatment in a 16-yr-old boy with
      neurologic presentation was analyzed and monitored. In the face of severe
      symptoms of chelator intolerance, a comparatively low dose of 100 mg of zinc has
      been administered for the entire 11-yr-long treatment. Considerable improvement
      of clinical status was achieved, with accompanying regression of central nervous
      system lesion. The parameters of copper metabolism were normalized with effective
      urine elimination. The low-dose oral zinc intake proved to be therapeutically
      effective, eliminating further copper tissue toxicity.

PMID- 11508633
TI  - Context and community.

PMID- 11508634
TI  - The effect of neighborhood-based community organizing: results from the Seattle
      Minority Youth Health Project.
AB  - OBJECTIVE: To evaluate the effect of a community mobilization and youth
      development strategy to prevent drug abuse, violence, and risky sexual activity.
      DATA SOURCES/STUDY SETTING: Primary surveys of youth, parents, and key
      neighborhood leaders were carried out at baseline (1994) and at the end of the
      intervention period (1997). The study took place in four intervention and six
      control neighborhoods in Seattle. STUDY DESIGN: The study was designed as a
      randomized controlled trial with neighborhood as the unit of randomization. The
      intervention consisted of a paid community organizer in each neighborhood who
      recruited a group of residents to serve as a community action board. Key
      variables included perceptions of neighborhood mobilization by youth, parents,
      and key neighborhood leaders. DATA COLLECTION/EXTRACTION METHODS: Youth surveys
      were self-administered during school hours. Parent and neighborhood leader
      surveys were conducted over the phone by trained interviewers. PRINCIPAL
      FINDINGS: Survey results showed that mobilization increased to the same degree in
      both intervention and control neighborhoods with no evidence of an overall
      intervention effect. There did appear to be a relative increase in mobilization
      in the neighborhood with the highest level of intervention activity. CONCLUSION:
      This randomized study failed to demonstrate a measurable effect for a community
      mobilization intervention. It is uncertain whether the negative finding was
      because of a lack of strength of the interventions or problems detecting
      intervention effects using individual-level closed-end surveys.

PMID- 11508635
TI  - Service delivery and community: social capital, service systems integration, and
      outcomes among homeless persons with severe mental illness.
AB  - OBJECTIVES: This study evaluated the influence of features of community social
      environment and service system integration on service use, housing, and clinical
      outcomes among homeless people with serious mental illness. STUDY SETTING: A one
      year observational outcome study was conducted of homeless people with serious
      mental illness at 18 sites. DATA SOURCES: Measures of community social
      environment (e.g., social capital) were based on local surveys and voting
      records. Housing affordability was assessed with housing survey data. Service
      system integration was assessed through interviews with key informants at each
      site to document interorganizational transactions. Standardized clinical measures
      were used to assess clinical and housing outcomes in face-to-face interviews.
      RESEARCH DESIGN: Structural equation modeling was used to determine the
      relationship between (1) characteristics of the social environment (social
      capital, housing affordability); (2) the level of integration of the service
      system for persons who are homeless in each community; (3) access to and use of
      services by individual clients; and (4) successful exit from homelessness or
      clinical improvement. PRINCIPAL FINDINGS: Social capital was associated with
      greater service systems integration, which was associated in turn with greater
      access to assistance from a public housing agency and to a greater probability of
      exiting from homelessness at 12 months. Housing affordability also predicted exit
      from homelessness. Neither environmental factors nor systems integration
      predicted outcomes for psychiatric problems, substance abuse, employment,
      physical health, or income support. CONCLUSION: Community social capital and
      service system integration are related through a series of direct and indirect
      pathways with better housing outcomes but not with superior clinical outcomes for
      homeless people with mental illness. Implications for designing improved service
      systems are discussed.

PMID- 11508636
TI  - An exploration of the complex relationship of socioecologic factors in the
      treatment and outcomes of acute myocardial infarction in disadvantaged
      populations.
AB  - OBJECTIVE: To examine the relationship of patients' socioeconomic status (SES) as
      measured by race, health insurance status, and median income by zip code to in
      hospital mortality of acute myocardial infarction (AMI), paying special attention
      to patients with multiple unfavorable socioeconomic risk factors. DATA
      SOURCES/STUDY SETTING: The data set was abstracted from patient-level hospital
      discharges in the Nationwide Inpatient Sample, Release 3, 1994. A total of 95,971
      AMI discharges in 11 states were extracted. STUDY DESIGN: The risk adjustment
      methodology was adapted from the California Hospital Outcomes Project. Risk
      factors included demographic and clinical characteristics. Patients in double
      jeopardy had inferior insurance status and lived in poorer neighborhoods.
      PRINCIPAL FINDINGS: Compared with patients with health care coverage under
      Medicare and private insurance uninsured AMI patients had the highest risk
      adjusted mortality odds and Medicaid AMI patients had the second highest odds.
      Probably because of the modest association of median income by zip code areas
      with mortality odds, the double jeopardy phenomenon was not observed. However,
      compared to patients who had two favorable SES attributes, patients who carried
      two unfavorable SES attributes had much higher mortality risk, more
      comorbidities, longer length of stay, and higher total hospital charges, while
      they received fewer AMI specialized procedures. Race did not seem to be a
      significant factor after adjustment for other SES attributes. CONCLUSIONS: SES is
      significantly related to the mortality of AMI patients. The disadvantaged
      patients receive fewer specialized procedures, possibly because of their higher
      levels of severity and financial barriers. The variation in mortality between
      patients who had favorable and unfavorable SES becomes wider when multiple
      socioeconomic risks are borne by the latter.

PMID- 11508637
TI  - Geographic variation in determinants of Medicare managed care enrollment.
AB  - OBJECTIVE: To examine the effect of adjusted average per capita cost (AAPCC) rate
      and volatility on Medicare risk plan enrollment at the county level. DATA
      SOURCES: Secondary data from the Health Care Financing Administration's office of
      managed care and other sources were merged to create comprehensive data on all
      Medicare risk plans in 3,069 of the 3,112 U. S. counties in December 1996. STUDY
      DESIGN: A two-step least squares regression was estimated to examine the effects
      of AAPCC rate and volatility, commercial HMO enrollment, market factors, and
      characteristics of the county population on Medicare HMO enrollment. The model
      was also used to simulate the effects of the Balanced Budget Act of 1997. Data
      from the Health Care Financing Administration were merged with other sources at
      the county level. The Federal Information Processing Standards code and a
      crosswalk file matching that code with the county name linked the data across
      sources. PRINCIPLE FINDINGS: The AAPCC rate has a small positive effect on the
      probability of Medicare HMO availability and enrollment. However, commercial HMO
      enrollment has a much stronger positive effect on Medicare HMO enrollment.
      Volatility has a negative effect on the probability of any Medicare HMO
      enrollment. CONCLUSIONS: The results suggest that payment changes enacted as part
      of the Balanced Budget Act will have a limited effect on Medicare HMO enrollment,
      especially in rural areas. Other policy changes are needed to stimulate Medicare
      HMO enrollment.

PMID- 11508638
TI  - The long-term effects of Medicaid managed care on obstetrics care in three
      California counties.
AB  - OBJECTIVE: To evaluate the long-term effects of Medicaid managed care (MMC) on
      obstetric service use and program costs in California. DATA SOURCES/STUDY
      SETTING: Longitudinal administrative data on Medi-Cal enrollment and claims and
      encounters related to pregnancy and delivery services were gathered from three
      counties--two long-standing MMC counties and one traditional fee-for-service
      Medicaid county--in California between 1987 and 1992. STUDY DESIGN: We studied
      Aid to Families with Dependent Children (AFDC) beneficiaries with live singleton
      vaginal deliveries with associated hospital stays of 14 days or less. Effects of
      managed care were examined with respect to prenatal visits, length of stay for
      delivery, maternal postpartum readmission rates, and total program expenditures.
      Multivariate analyses examined how the relative effect of managed care on service
      use and program expenditures in each MMC county evolves over time in comparison
      to fee-for-service. We controlled for length of Medi-Cal enrollment prior to
      delivery, data censoring, and individual characteristics such as race and age.
      PRINCIPAL FINDINGS: Prenatal care use is consistently lower in the MMC counties,
      although all three counties' prenatal care provision is well below the national
      standard. Drastic increases in one-day-stay deliveries were found: up to almost
      50 percent of deliveries in MMC counties were one-day stays. Program cost savings
      associated with MMC enrollment are unambiguous. CONCLUSIONS: MMC cost savings
      might have come at the expense of reduced provision of prenatal care and shorter
      delivery length of stay. Future studies should verify any possible causal link
      and the effects on maternal and infant health outcomes.

PMID- 11508639
TI  - The development of a survey instrument for community health improvement.
AB  - OBJECTIVE: To develop a survey instrument that could be used both to guide and
      evaluate community health improvement efforts. DATA SOURCES/STUDY SETTING: A
      randomized telephone survey was administered to a sample of about 250 residents
      in two communities in Lehigh Valley, Pennsylvania in the fall of 1997. METHODS:
      The survey instrument was developed by health professionals representing diverse
      health care organizations. This group worked collaboratively over a period of two
      years to (1) select a conceptual model of health as a foundation for the survey;
      (2) review relevant literature to identify indicators that adequately measured
      the health constructs within the chosen model; (3) develop new indicators where
      important constructs lacked specific measures; and (4) pilot test the final
      survey to assess the reliability and validity of the instrument. PRINCIPAL
      FINDINGS: The Evans and Stoddart Field Model of the Determinants of Health and
      Well-Being was chosen as the conceptual model within which to develop the survey.
      The Field Model depicts nine domains important to the origins and production of
      health and provides a comprehensive framework from which to launch community
      health improvement efforts. From more than 500 potential indicators we identified
      118 survey questions that reflected the multiple determinants of health as
      conceptualized by this model. Sources from which indicators were selected include
      the Behavior Risk Factor Surveillance Survey, the National Health Interview
      Survey, the Consumer Assessment of Health Plans Survey, and the SF-12 Summary
      Scales. The work group developed 27 new survey questions for constructs for which
      we could not locate adequate indicators. Twenty-five questions in the final
      instrument can be compared to nationally published norms or benchmarks. The final
      instrument was pilot tested in 1997 in two communities. Administration time
      averaged 22 minutes with a response rate of 66 percent. Reliability of new survey
      questions was adequate. Face validity was supported by previous findings from
      qualitative and quantitative studies. CONCLUSIONS: We developed, pilot tested,
      and validated a survey instrument designed to provide more comprehensive and
      timely data to communities for community health assessments. This instrument
      allows communities to identify and measure critical domains of health that have
      previously not been captured in a single instrument.

PMID- 11508640
TI  - Risk adjustment alternatives in paying for behavioral health care under Medicaid.
AB  - OBJECTIVE: To compare the performance of various risk adjustment models in
      behavioral health applications such as setting mental health and substance abuse
      (MH/SA) capitation payments or overall capitation payments for populations
      including MH/SA users. DATA SOURCES/STUDY DESIGN: The 1991-93 administrative data
      from the Michigan Medicaid program were used. We compared mean absolute
      prediction error for several risk adjustment models and simulated the profits and
      losses that behavioral health care carve outs and integrated health plans would
      experience under risk adjustment if they enrolled beneficiaries with a history of
      MH/SA problems. Models included basic demographic adjustment, Adjusted Diagnostic
      Groups, Hierarchical Condition Categories, and specifications designed for
      behavioral health. PRINCIPAL FINDINGS: Differences in predictive ability among
      risk adjustment models were small and generally insignificant. Specifications
      based on relatively few MH/SA diagnostic categories did as well as or better than
      models controlling for additional variables such as medical diagnoses at
      predicting MH/SA expenditures among adults. Simulation analyses revealed that
      among both adults and minors considerable scope remained for behavioral health
      care carve outs to make profits or losses after risk adjustment based on
      differential enrollment of severely ill patients. Similarly, integrated health
      plans have strong financial incentives to avoid MH/SA users even after
      adjustment. CONCLUSIONS: Current risk adjustment methodologies do not eliminate
      the financial incentives for integrated health plans and behavioral health care
      carve-out plans to avoid high-utilizing patients with psychiatric disorders.

PMID- 11508641
TI  - Measuring clinical performance: comparison and validity of telephone survey and
      administrative data.
AB  - OBJECTIVE: To compare and validate self-reported telephone survey and
      administrative data for two Health Plan Employer Data and Information Set (HEDIS)
      performance measures: mammography and diabetic retinal exams. DATA SOURCES/STUDY
      SETTING: A telephone survey was administered to approximately 700 women and 600
      persons with diabetes randomly chosen from each of two health maintenance
      organizations (HMOs). STUDY DESIGN: Agreement of survey and administrative data
      was assessed by using kappa coefficients. Validity measures were assessed by
      comparing survey and administrative data results to a standard: when the two
      sources agreed, that was accepted as the standard; when they differed,
      confirmatory information was sought from medical records to establish the
      standard. When confirmatory information was not available ranges of estimates
      consistent with the data were constructed by first assuming that all persons for
      whom no information was available had received the service and alternately that
      they had not received the service. PRINCIPAL FINDINGS: The kappas for mammography
      were .65 at both HMOs; for retinal exam they were .38 and .40. Sensitivity for
      both data sources was consistently high. However, specificity was lower for
      survey (range .44 to .66) than administrative data (.99 to 1.00). The positive
      predictive value was high for mammography using either data source but differed
      for retinal exam (survey .69 to .78; administrative data .99 to 1.00).
      CONCLUSIONS: Administrative and survey data performed consistently in both HMOs.
      Although administrative data appeared to have greater specificity than survey
      data the validity and utility of different data sources for performance
      measurement have only begun to be explored.

PMID- 11508642
TI  - Effects of exercise training of 8 weeks and detraining on plasma levels of
      endothelium-derived factors, endothelin-1 and nitric oxide, in healthy young
      humans.
AB  - Vascular endothelial cells produce nitric oxide (NO), which is a potent
      vasodilator substance and has been proposed as having antiatherosclerotic
      property. Vascular endothelial cells also produce endothelin-1 (ET-1), which is a
      potent vasoconstrictor peptide and has potent proliferating activity on vascular
      smooth muscle cells. Therefore, ET-1 has been implicated in the progression of
      atheromatous vascular disease. Because exercise training has been reported to
      produce an alteration in the function of vascular endothelial cells in animals,
      we hypothesized that exercise training influences the production of NO and ET-1
      in humans. The purpose of the present study was to examine whether chronic
      exercise could influence the plasma levels of NO (measured as the stable end
      product of NO, i.e., nitrite/nitrate [NOx]) and ET-1 in humans. Eight healthy
      young subjects (20.3 +/- 0.5 yr old) participated in the study and exercised by
      cycling on a leg ergometer (70% VO2max for 1 hour, 3-4 days/week) for 8 weeks.
      Venous plasma concentrations of NOx and ET-1 were measured before and after
      (immediately before the end of 8-week exercise training) the exercise training,
      and also after the 4th and 8th week after the cessation of training. The VO2max
      significantly increased after exercise training. After the exercise training, the
      plasma concentration of NOx significantly increased (30.69 +/- 3.20 vs. 48.64 +/-
      8.16 micromol/L, p < 0.05), and the plasma concentration of ET-1 significantly
      decreased (1.65 +/- 0.14 vs. 1.23 +/- 0.12 pg/mL, p < 0.05). The increase in NOx
      level and the decrease in ET-1 level lasted to the 4th week after the cessation
      of exercise training and these levels (levels of NOx and ET-1) returned to the
      basal levels (the levels before the exercise training) in the 8th week after the
      cessation of exercise training. There was a significant negative correlation
      between plasma NOx concentration and plasma ET-1 concentration. The present study
      suggests that chronic exercise causes an increase in production of NO and a
      decrease in production of ET-1 in humans, which may produce beneficial effects
      (i.e., vasodilative and antiatherosclerotic) on the cardiovascular system.

PMID- 11508643
TI  - The effects of hydraulic pressure on atrial natriuretic peptide during
      rehabilitative head-out water immersion.
AB  - To study the hydraulic effects of subtotal immersion as a rehabilitative
      hydrotherapy, we examined the change in serum levels of atrial natriuretic
      peptide, catecholamine, cortisol and interleukins in 12 healthy volunteers. The
      subjects soaked in 42 degrees C water of 70 cm depth up to chin level in the
      upright seated position for 10 min. The serum level of atrial natriuretic peptide
      increased significantly 15 min after the start of subtotal immersion, though that
      of brain natriuretic peptide did not change. The serum dopamine level increased
      significantly 15 min after immersion, though neither the serum epinephrine nor
      norepinephrine levels did. In addition, 30 min after the start of immersion, the
      serum levels of atrial natriuretic peptide and dopamine decreased to those before
      immersion. The serum level of adrenocorticotropic hormone increased 15 min after
      immersion, though those of cortisol, interleukin-1beta and 6, and tumor necrotic
      factor-alpha did not change. It is suggested that 10-min head-out water immersion
      increased atrial natriuretic peptide partly due to increased venous return or
      right atrial load by hydraulic pressure.

PMID- 11508644
TI  - The opioid peptide analogue biphalin induces less physical dependence than
      morphine.
AB  - We compared the physical dependence liability of biphalin, a dimeric enkephalin
      analogue that possesses high antinociceptive activity, with that of morphine in
      equipotent intravenous doses. Naloxone challenge produced severe withdrawal signs
      after a 5-day infusion of morphine but only minor withdrawal signs after a 5-day
      biphalin infusion. In a cross-dependence study, biphalin did not suppress body
      weight loss after morphine withdrawal, but successfully suppressed weight loss
      after pentazocine withdrawal. These data support consideration of biphalin as a
      new analgesic with a novel pharmacological profile and minimum dependence
      liability.

PMID- 11508645
TI  - Spirulina maxima prevents fatty liver formation in CD-1 male and female mice with
      experimental diabetes.
AB  - The dietary administration of 5% Spirulina maxima (SM) during four weeks to
      diabetic mice, starting one week after a single dose of alloxan, 250 mg/Kg body
      weight, prevented fatty liver production in male and female animals. The main
      action of SM was on triacylglycerol levels in serum and liver. There was also a
      moderate hypoglycemia in male mice. The thiobarbituric acid reactive substances
      also decreased in serum and liver after SM administration. There was also a
      decrease in the percentage of HDL in diabetic mice that was reverted by the SM
      administration. The sum of LDL + VLDL percentages was also partially normalized
      in diabetic animals by the SM administration. An additional observation was the
      lower incidence of adherences between the liver and the intestine loops in the
      diabetic mice treated with SM compared with diabetic mice without SM. Male and
      female mice showed differences to diabetes susceptibility and response to SM, the
      female being more resistant to diabetes induction by alloxan and more responsive
      to the beneficial effects of SM. It is worth future work of SM on humans looking
      for better quality of life and longer survival of diabetic patients.

PMID- 11508646
TI  - Hyperglycemia in diabetic rats reduces the glutathione content in the aortic
      tissue.
AB  - The glutathione redox cycle plays a major role in scavenging hydrogen peroxide
      (H2O2) under physiological conditions. Recently, we demonstrated that a high
      glucose concentration in the culture medium reduced the level of H2O2 scavenging
      activity of human vascular smooth muscle cells (hVSMCs). We also showed that a
      high glucose concentration reduced the intracellular glutathione (GSH) content
      and the rate of uptake of cystine, which itself is a rate-limiting factor that
      maintains the GSH level (FEBS Lett.421: 19-22,1998). In the present study, we
      investigated whether the hyperglycemic condition in diabetic rats impairs the
      glutathione content in the aortic tissue in vivo. Wistar rats were divided into
      the following three groups: streptozotocin-induced diabetic rats (STZ-D, n=7),
      insulin-treated STZ-D rats (I-STZ-D, n=8), and non-diabetic controls (C, n=7).
      Fourteen days after streptozotocin injection, the aortic tissue was extracted and
      the GSH content in the aortic tissue was measured. Furthermore, the relationship
      between the GSH content in the aortic tissue and blood glucose level in Otsuka
      Long-Evans Tokushima Fatty (OLETF) rats aged 30 weeks, which developed diabetes
      spontaneously, was investigated. The GSH content in the aortic tissue of the STZ
      D group (0.99+/-0.14 nmol/mg protein) was significantly lower than that of the
      control group (1.68+/-0.15 nmol/mg protein). Insulin treatment to the diabetic
      rats restored the GSH content in the aortic tissue (I-STZ-D group; 1.45+/-0.11
      nmol/mg protein). Among the 22 Wistar rats, the GSH content in the aortic tissue
      was negatively correlated with the blood glucose level (r=-0.69, p<0.01, n=22).
      Among the OLETF rats, a similar negative correlation between the GSH content in
      the aortic tissue and blood glucose level was seen (r=-0.64, p<0.05, n=10). We
      demonstrated in vivo that the hyperglycemic condition in STZ-induced diabetic
      Wistar rats and OLETF rats reduced the GSH content in aortic tissue. This
      suggested reduced glutathione redox cycle function of aorta.

PMID- 11508647
TI  - Differences between the tolerance characteristics of two anticonvulsant
      benzodiazepines in the amygdaloid-kindled rat.
AB  - The characteristics of the development of tolerance to the anticonvulsant effects
      of chronic treatment by dipotassium clorazepate and diazepam using amygdaloid
      kindled rats were investigated. Dipotassium clorazepate (5 mg/kg) or diazepam (5
      mg/kg) were intraperitoneally administered for 10 consecutive days. Tolerance to
      the anticonvulsant effect of dipotassium clorazepate developed in seizure stage
      on day 6, after-discharge duration on day 7 and seizure latency on day 4. In
      contrast, tolerance to the effects of diazepam developed more rapidly in seizure
      stage on day 4, after-discharge duration on day 4 and seizure latency on day 3.
      Thus tolerance to the anticonvulsive effect of dipotassium clorazepate developed
      relatively slower than that to diazepam. All rats had stage 5 convulsions 24 hr
      after cessation of the administration of dipotassium clorazepate and diazepam.
      Concomitant determinations of plasma concentrations of the main metabolite of
      dipotassium clorazepate and diazepam, desmethyldiazepam, showed no statistical
      difference during treatment, suggesting that the developed tolerance was not
      metabolic but functional.

PMID- 11508648
TI  - Resveratrol reduction of infarct size in Long-Evans rats subjected to focal
      cerebral ischemia.
AB  - Resveratrol is found in a wide variety of plant species. It is present in the
      seeds and skin of grapes and constitutes one of the major components of red wine.
      This study was undertaken to evaluate whether resveratrol could effectively
      suppress infarct size from the damaging effects of focal cerebral ischemia. The
      middle cerebral artery was occluded for 1 hr and 24 hr reperfusion in
      anesthetized Long-Evans rats. In pretreatment or treatment groups, resveratrol,
      at dosages of 10(-6), 10(-7), 10(-8) and 10(-9) g/kg, was intravenous injected 15
      minutes before middle cerebral artery (MCA) occlusion or when the common carotid
      arteries clips were removed respectively. Pretreatment or treatment of
      resveratrol (10(-6), 10(-7), 10(-8) and 10(-9) g/kg) did not produce any changes
      in pH, blood gases, heart rate or mean arterial blood pressure, but it
      significantly reduced the total volume of infarction at the doses 10(-6) and 10(
      7) g/kg. Our study suggests resveratrol is a potent neuroprotective agent in
      focal cerebral ischemia. Its beneficial effects may be related to its anti
      platelet aggregation activity, vasodilating effect, antioxidant property or by
      all mechanisms together.

PMID- 11508649
TI  - Dexamethasone suppresses iNOS gene expression by inhibiting NF-kappaB in vascular
      smooth muscle cells.
AB  - Bacterial lipopolysaccharide (LPS) and other immunostimulants induce an isoform
      of nitric oxide synthase (iNOS) gene expression in vascular smooth muscle cells
      (VSMC). This process is dependent on nuclear factor-kappa B (NF-kappaB)
      activation and is suppressed by glucocorticoids. The aim of this study was to
      investigate the molecular mechanisms of inhibition of iNOS expression by the
      synthetic glucocorticoid, dexamethasone (DEX), in rat VSMC. Treatment of VSMC
      with LPS plus interferon-gamma (LPS/IFN) caused activation of NF-kappaB and the
      iNOS promoter. LPS/IFN induced iNOS mRNA and NO synthesis. DEX markedly depressed
      LPS/IFN-stimulated iNOS mRNA expression and NO production. DEX also suppressed
      LPS/IFN-stimulated activity of a 1.7-kb iNOS promoter, indicating that the
      inhibition of iNOS expression by DEX occurs at the level of transcription. NF
      kappaB activation by LPS/IFN was repressed by DEX. The inhibition of NF-kappaB by
      DEX exhibited dose-dependent kinetics, which corresponded to DEX suppression of
      iNOS promoter activation, iNOS mRNA expression, and NO production. However,
      activation of activator protein-1 (AP-1), which is also contained in the iNOS
      promoter, was not enhanced by LPS/IFN or inhibited by DEX. Thus, glucocorticoids
      appear to block iNOS expression, at least in part, through inhibition of NF
      kappaB activation, which results in decreased NO production.

PMID- 11508650
TI  - Age-related reduction of extrastriatal dopamine D2 receptor measured by PET.
AB  - Although the aging effect of dopamine D2 receptor in the striatum is well
      documented, the effect of age on the extrastriatal dopamine D2 receptor has not
      been fully examined. Since the density of extrastriatal dopamine D2 receptor is
      very low, suitable ligands are limited. In this study, we used [11C]FLB 457 to
      quantify the extrastriatal dopamine D2 receptor in the living human brain. Twenty
      seven healthy male subjects aged from 21 to 82 years participated in the positron
      emission tomography study. Extrastriatal [11C]FLB 457 binding was quantified with
      a reference tissue model using cerebellum as a reference region. Binding
      potentials corresponding to Bmax/Kd were used to evaluate age-related change. We
      found age-related decreases of D2 receptor binding in all measured extrastriatal
      regions. The decrease of D2 receptor binding was 13.8% per decade in frontal
      cortex, 12.0% in temporal cortex, 13.4% in parietal cortex, 12.4% in occipital
      cortex, 12.2% in hippocampus, and 4.8% in thalamus. These findings suggest that
      the amounts of D2 receptor declines in all brain regions as part of the normal
      aging process.

PMID- 11508651
TI  - A possible indirect sympathomimetic action of metformin in the arterial vessel
      wall of spontanously hypertensive rats.
AB  - The antidiabetic drug metformin (MF) typically achieves only micromolar levels in
      plasma with normal therapeutic use. However, it is also known to accumulate in
      various tissues up to several times higher after standard oral dosing and we now
      have evidence from both in vivo and in vitro experiments with spontaneously
      hypertensive rats (SHR) that millimolar levels stimulate release of
      norepinephrine (NE) from vascular sympathetic nerve endings (SNEs). As shown in
      the present work with SHR tail arterial tissue (rich in SNEs), the known
      vasodilator effect of millimolar levels of MF on the smooth muscle (even if
      contracted with a nonadrenergic agonist), is attenuated by the presence of the
      SNEs unless phentolamine (an alpha receptor blocker) is present. We reasoned that
      the mechanism for this apparent NE-releasing action of MF is not exocytotic
      release as that would require depolarization of the neuronal cell membranes in
      SNEs, and MF at millimolar levels is known to repolarize (not depolarize)
      membranes of other cells. Thus, we tested the possibility that MF releases NE by
      an indirect sympathomimetic-like action. Such an action should be amplified by
      monoamine oxidase inhibitors (e.g. iproniazid) and blocked by NE-carrier
      inhibitors (e.g. desipramine). Accordingly, we found that the abovementioned
      attenuating effect of intact SNEs on MF's relaxation of SHR tail arterial tissue
      (compared to tissues in which SNEs were experimentally removed with 6
      hydroxydopamine) was amplified nearly 3-fold by iproniazid (p<0.05) and blocked
      by desipramine (p<0.05). These results support an indirect sympathomimetic action
      of MF and raise the question whether commonly used antidepressants with
      properties similar to iproniazid and desipramine might alter MF's beneficial
      vasodilatory (and thus antihypertensive) effectiveness in diabetic patients with
      hypertension.

PMID- 11508652
TI  - Chronic cocaine administration decreases the functional coupling of GABA(B)
      receptors in the rat ventral tegmental area as measured by baclofen-stimulated
      35S-GTPgammaS binding.
AB  - Results of numerous studies indicate that the inhibitory neurotransmitter gamma
      aminobutyric acid (GABA) modulates central dopamine systems, and that GABA(B)
      receptors may play a primary role in decreasing dopamine release. To determine if
      chronic cocaine administration alters the functional coupling of GABA(B)
      receptors to G-proteins in central dopamine systems, male F-344 rats received
      cocaine (15 mg/kg/injection) or saline three times a day at hourly intervals for
      fourteen consecutive days. Rats were decapitated one hour after the last
      injection and crude membrane preparations were made from the substantia nigra,
      caudate-putamen, ventral tegmental area, nucleus accumbens, and frontal cortex of
      individual rats. The ability of the specific GABA(B) receptor agonist baclofen to
      stimulate 35S-GTPgammaS binding in each of these regions was determined for
      individual animals. Additionally, baclofen-stimulated 35S-GTPgammaS binding in
      each of these regions in rats that received cocaine was compared to baclofen
      stimulated 35S-GTPgammaS binding in rats that received control injections of
      saline. The EC50 of baclofen and maximal baclofen-stimulated 35S-GTPgammaS
      binding over basal levels were determined in each brain region in the saline
      group and in the cocaine group. Two-way ANOVA revealed a significant decrease in
      GABA(B) receptor-stimulated 35S-GTPgammaS binding in the ventral tegmental area
      of the cocaine group compared to the saline group. These data suggest that
      chronic exposure to cocaine decreases the functional coupling of GABA(B)
      receptors to G-proteins selectively in the ventral tegmental area. This finding
      may have implications in the augmented extracellular dopamine levels seen in the
      nucleus accumbens of rats that have been sensitized to cocaine.

PMID- 11508653
TI  - A role for dietary fat in leptin receptor, OB-Rb, function.
AB  - Leptin is a hormone believed to control appetite and regulate body weight via
      receptors in the hypothalamus. Much is known about the structure of the
      functional, or long, form of the leptin receptor, OB-Rb. However, the mechanism
      by which the receptor regulates leptin's biological action is unknown. Both the
      type and amount of dietary fat have been shown to affect factors involved in OB
      Rb binding and signaling, as well as the morphology of hypothalamic cell
      membranes. Thus, the following review article examines possible mechanisms by
      which dietary fat may affect OB-Rb functioning at the hypothalamic level. Dietary
      fat can alter the fatty acid make-up of membranes, such as the
      polyunsaturated:saturated fat ratio, changing membrane fluidity and possibly
      leading to an enhancement or impairment of the structure and/or function of any
      membrane-associated receptor complexes. Dietary fat also interferes in
      biochemical pathways involving leptin, OB-Rb, and other neurons containing
      neuropeptides under OB-Rb's control, such as neuropeptide Y (NPY),
      proopiomelanocortin (POMC), and cocaine- and amphetamine-regulated transcript
      (CART). Increased monounsaturated fat increases cyclic adenosine monophosphate
      (cAMP) levels, possibly reducing mitogen-activated protein kinase (MAPK)
      activation and interrupting leptin signaling through Janus kinase/signal
      tranducers and activators of transcription (JAK/STAT) pathways. Dietary induced
      alterations in hypothalamic cell membranes, SNS activity, or other factors
      involved in OB-Rb function form a possible basis for the control of leptin's
      effects on body composition and appetite. Improving the biological activity of
      leptin by diet modification may exist as a practical strategy for the treatment
      of obesity and related disorders.

PMID- 11508654
TI  - Effect of intranasal sumatriptan on gastric tone and sensitivity to distension.
AB  - Sumatriptan is able to improve symptoms of early satiety in dyspeptic patients by
      relaxing the gastric fundus. The aim of this study was to verify the efficacy of
      intranasal administration of sumatriptan on gastric sensory motor function, in
      order to provide a new pharmacotherapeutic approach to functional dyspepsia.
      Thirteen healthy subjects were investigated twice on separate days. A gastric
      barostat was used to study the effect of placebo and sumatriptan, 20 mg
      intranasally, on basal fundic tone. In addition, stepwise isobaric distensions
      were performed and perception was measured before and after administration of
      drugs. Placebo had no effect on gastric tone and on perception. Sumatriptan
      caused a small, but short-lasting gastric relaxation and had no significant
      effect on sensitivity to distension and gastric compliance. Unlike the
      subcutaneous formulation, the intranasal administration of sumatriptan had no
      effect on gastric sensory motor functions, and this probably reflects a low
      biovailability of intranasally administered sumatriptan.

PMID- 11508655
TI  - Gastric neuropeptides and gastric motor abnormality in streptozotocin-induced
      diabetic rats: observation for four weeks after streptozotocin.
AB  - Alterations of gastric calcitonin gene-related peptide and substance P content
      and gastric emptying in early stages of streptozotocin-induced diabetic rats were
      investigated. Diabetes was induced by intravenous injection of streptozotocin (50
      mg/kg) in male Wistar rats. Gastric emptying of phenol red solution and
      calcitonin gene-related peptide and substance P content of gastric walls,
      measured by radioimmunoassay, was assessed two and four weeks after
      streptozotocin injection. Gastric emptying two weeks after streptozotocin was
      delayed (32+/-9%) and that four weeks after was enhanced (73+/-2%) compared with
      nondiabetic control rats (50+/-3%). Calcitonin gene-related peptide content of
      the gastric antrum and corpus was increased two weeks after and decreased four
      weeks after streptozotocin, while gastric substance P content was not changed at
      any time in diabetic rats. Insulin treatment reversed alterations of gastric
      emptying and calcitonin gene-related peptide content. The delayed gastric
      emptying in two-week diabetic rats was reversed by CGRP antagonist and the
      enhanced gastric emptying in four-week diabetic rats was reversed by CGRP
      pretreatment. These results suggest a possible relationship between gastric
      calcitonin gene-related peptide and abnormal gastric motility in diabetic state.

PMID- 11508657
TI  - Occurrence of esophageal granular cell tumors in The Netherlands between 1988 and
      1994.
AB  - Granular cell tumors (GCT) of the esophagus are rare. The tumor is generally
      beleived to be of neurogenic origin and shows a malignant course in 2-4% of
      cases. No unanimity has been reached regarding the management of this tumor. A
      national survey was conducted on the incidence of GCT of the esophagus, related
      symptoms, management, and follow-up. A national survey was performed on all newly
      registered esophageal GCTs in the PALGA system (Dutch register of all pathology
      diagnoses) for seven consecutive years (1988-1994). Fifty-two new cases (17 men,
      35 women; median age 46 years, range 22-77 years) were registered. In 44 cases
      clinical data could be obtained (survey response 85%). The majority of the GCTs
      were solitary (42/44) and localized in the distal esophagus (33/44). At endoscopy
      the size of the tumor was estimated at <5 mm in 50%, 5-10 mm in 25%, and 10-30 mm
      in 18%. Most patients (40/44) presented with nonspecific gastrointestinal
      symptoms, only four had dysphagia (tumor size >1 cm). No malignancies were
      reported. Management of the tumor included excisional biopsy (1/44), endoscopic
      polypectomy (3/44), and surgical excision (1/44). Endoscopic follow up (1-60
      months) in 16 out of 17 patients left untreated showed either a stable tumor size
      or regression of the tumor. In one case with multiple GCT's a slight tumor growth
      was seen after a follow-up period of 48 months. Esophageal GCTs in the
      Netherlands are rare, and mostly diagnosed incidentally. Most patients suffer
      from nonspecific symptoms; dysphagia occurs only with tumors >1 cm. The usual
      clinical course of esophageal GCTs is benign. Patients without dysphagia probably
      do not require routine endoscopic follow-up, provided they are instructed to
      contact their physician, once dysphagia develops.

PMID- 11508656
TI  - Gastric emptying and gastrointestinal transit of liquid throughout the first
      month after thoracic spinal cord transection in awake rats.
AB  - Spinal cord transection (SCT) inhibits gastrointestinal motility in awake rats.
      We studied the gastric emptying (GE) and gastrointestinal transit of liquid
      throughout the first month after thoracic SCT. Male Wistar rats (N = 66) were
      submitted to laminectomy followed or not by complete SCT between T4 and T5
      vertebrae. Phenol red recovery in the stomach, proximal, mid-and distal small
      intestine was determined 1, 7, 10, 15, and 30 days thereafter. Gastric recovery
      increased by 51.2 and 38.9% and mid-intestinal recovery decreased by 45.5 and
      66.6% at one and seven days after SCT (P < 0.05). Proximal small intestine
      recovery increased by 45.9% 10 days after SCT but no inhibition of
      gastrointestinal motility was observed thereafter. Stool output significantly
      decreased in the first seven days after SCT (P < 0.05). In summary,
      gastrointestinal motility in awake rats is inhibited throughout the first 10 days
      after thoracic SCT but not thereafter.

PMID- 11508659
TI  - Prognostic factors in hepatic metastases of colorectal carcinoma:
      immunohistochemical analysis of tumor biological factors.
AB  - The present study was designed to provide a systemic analysis of prognosis in 62
      patients who underwent hepatic resection for colorectal liver metastasis. The
      analyzed factors included microvessel counts stained by CD34 and expression of
      two adhesion molecules, E-cadherin and CD44 variant exon 6-(v6) in these tumors.
      No significant factors related to recurrence were identified and only negative
      expression of CD44v6 tended to correlate with recurrence (P = 0.075). A short
      disease-free period to recurrence was noted in patients with high CEA levels (>10
      ng/ml) and H2/3 classification. A short surgical margin, H2/3 classification,
      high microvessel counts (>60/field, x200), and negative expression of CD44v6 and
      E-cadherin tended to be associated with poor prognosis. A high microvessel count
      was the most significant prognostic factor by multivariate Cox proportional
      hazards regression model. Hepatic resection without tumor exposure and a careful
      follow-up in cases identified with poor prognostic factors are necessary.

PMID- 11508658
TI  - Relationship between grade of microsatellite instability and target genes of
      mismatch repair pathways in sporadic colorectal carcinoma.
AB  - Microsatellite instability (MSI) induces carcinoma through the alteration of
      target genes; TGF-beta RII, BAX, IGFIIR, hMSH3, and hMSH6. The grade of M

PMID- 11508660
TI  - Expression of embryonic-form smooth muscle myosin heavy chain in a
      gastrointestinal stromal tumor of the greater omentum.

PMID- 11508661
TI  - Brain-derived neurotrophic factor (BDNF) is upregulated and associated with pain
      in chronic pancreatitis.
AB  - Our purpose was to investigate brain-derived neurotrophic factor (BDNF) in
      chronic pancreatitis (CP) in comparison with the normal pancreas and to evaluate
      its association with pain. By immunohistochemistry, in the normal pancreas BDNF
      immunoreactivity was moderately present in the cytoplasm of most ductal cells and
      weakly present in most acinar cells, islet cells, nerve fibers (including
      perineurium), and ganglia cells. In contrast, in CP intense immunostaining of
      BDNF was present in most cells of ductular complexes and in the perineurium of
      enlarged nerves. Moderate immunostaining of BDNF was found in degenerating acinar
      cells and islet cells. In addition, moderate immunoreactivity of BDNF was also
      detected in most enlarged nerve fibers and intrinsic pancreatic ganglia cells in
      CP samples. Western blot analysis also revealed 5.6-fold higher BDNF levels in CP
      samples (P < 0.01) compared with normal pancreas samples. The expression level of
      BDNF was positively correlated with pain intensity (P < 0.01) and pain frequency
      (P < 0.01) of CP patients. Furthermore, there was a significant relationship (r =
      0.68, P < 0.01) between the BDNF immunostaining and the global pain scores. BDNF
      is increased in CP. Its association with pain suggests that it functions as a
      peripheral and central pain modulator, as reported previously in other
      inflammatory disorders.

PMID- 11508662
TI  - P8 expression is induced in acinar cells during chronic pancreatitis.
AB  - The p8 gene is barely expressed in the normal pancreas, but is overexpressed in
      acute pancreatitis. To elucidate the dynamic expression of p8 mRNA and its
      significance in the course of chronic pancreatitis, we investigated the p8
      expression in spontaneous chronic pancreatitis in the WBN/Kob rat as well as in
      humans and arginine-treated rat pancreatic acinar AR4-2J cells. p8 mRNA was
      significantly increased at 12 weeks when chronic pancreatitis first appeared in
      the WBN/Kob rats. p8 was immunolocalized in the acinar cell nuclei. Acinar cell
      apoptosis was significantly increased at 12 and 20 weeks in the WBN/Kob rats. In
      AR4-2J cells, p8 mRNA was significantly induced at 4 hr after arginine addition.
      Apoptosis of AR4-2J cells was not increased during the strong expression of p8
      mRNA. These results suggest that p8 is induced in the acinar cells during chronic
      pancreatitis as the self-defence mechanism against proapoptotic insults.

PMID- 11508663
TI  - Cytokine mRNA levels and lymphocyte infiltration in pancreatic tissue during
      experimental chronic pancreatitis induced by dibutyltin dichloride.
AB  - There is little information available regarding the role of inflammatory cells in
      the pathogenesis of chronic pancreatitis. Therefore, we analyzed the local
      cytokine profile and infiltrating lymphocytes in a rat model of chronic
      pancreatitis. Experimental pancreatitis was induced by a single intravenous
      application of dibultyltin dichloride (DBTC). During a time course of two months
      we observed the mRNA expression of cytokines using competitive RT-PCR.
      Lymphocytes were characterized by immunohistochemistry, FACS analysis, and the
      lymphocyte proliferation test. IL-1beta, IL-6, IL-5, and IL-10 were immediately
      up-regulated in the acute phase of disease, while lymphocyte-restricted
      expression of IL-2, IL-2R, and IFN-y was only found in the chronic course. Among
      the infiltrating lymphocytes, CD4+ cells dominated, but during the chronic
      process there was an increase of CD8+ cells, resulting in a reduced CD4/CD8
      ratio. Mitogen-induced activation of isolated mesenteric lymph node cells
      increased during the chronic inflammation. Our results suggest that in
      experimental pancreatitis acute inflammatory reactions are followed by a T
      lymphocyte-mediated process.

PMID- 11508664
TI  - Hyperbaric oxygen prevents bacterial translocation in rats with obstructive
      jaundice.
AB  - This study was designed to demonstrate bacterial translocation following bile
      duct ligation and investigate preventive effects of hyperbaric oxygen on
      obstructive jaundice-related bacterial translocation in an animal model.
      Hyperbaric oxygen treatment significantly reduced the endogenous colony counts in
      distal ileum of normal rats both in the short (two days) and long (seven days)
      term. Endogenous bacteria in distal ileum significantly increased in bile duct
      ligated rats in the short and long term, and presence of bacterial translocation
      was proven by bacterial growth in mesenteric lymph nodes, liver, spleen, and
      blood. Short- and long-term hyperbaric oxygen treatments significantly reduced
      the intestinal colony counts and prevented the bacterial translocation almost
      completely in rats with bile duct ligation. It is concluded that obstructive
      jaundice causes bacterial overgrowth and translocation, and hyperbaric oxygen
      treatment can prevent both bacterial overgrowth and translocation effectively.

PMID- 11508665
TI  - Effect of ischemia-reperfusion on bile canalicular F-actin microfilaments in
      hepatocytes of human liver allograft: image analysis by confocal laser scanning
      microscopy.
AB  - We studied and quantified the effect of ischemia-reperfusion on hepatic F-actin
      on bile canalicular and basolateral membranes in human liver allografts by means
      of confocal laser scanning microscopy imaging. The phalloidin-FITC staining of F
      actin was normal in liver hepatocytes before reperfusion but decreased
      significantly after reperfusion (by 25% of controls). These results indicate that
      hepatic F-actin alteration is produced during the reperfusion phase. This
      modification, probably induced by reactive oxygen species, could impair bile
      canalicular contraction and tight junction permeability and consequently bile
      secretion in the postoperative period.

PMID- 11508666
TI  - Expression of proinflammatory cytokines and their inhibitors during the course of
      spontaneous bacterial peritonitis.
AB  - The aim of this work was the evaluation, in cirrhotic patients with noninfected
      ascites and with spontaneous bacterial peritonitis (SBP), of serum and ascitic
      fluid levels of proinflammatory cytokines [interleukin (IL) 1-beta, tumor
      necrosis factor alpha (TNF-alpha), and IL6] and antiinflammatory compounds [IL10,
      soluble IL-1 receptor antagonist (sIL-1Ra), soluble receptors of TNF p55 and p75
      (sTNFR55 and sTNFR75), and soluble receptor of IL6 (sIL6R)], as well as their
      relationship with the outcome of the infection in those with SBP. These molecules
      were assayed by ELISA in noninfected cirrhotic controls (n = 15), patients with
      SBP (n = 32), and healthy controls (n = 20). Serum levels of IL6 and of the
      majority of antiinflammatory mediators, sIL1Ra, sTNFR75, and sIL6R, were higher
      in control cirrhotic patients compared to healthy subjects. SBP was associated
      with significantly elevated ascitic fluid levels of every one of the
      proinflammatory cytokines compared to those in cirrhotic controls. Also, serum
      levels of IL10 and both TNF receptors and ascitic fluid levels of sIL1Ra and
      sTNFR55 were higher in patients with SBP compared to cirrhotic controls. Ascitic
      fluid levels of proinflammatory cytokines decreased rapidly after resolution of
      the infection; however, nonsignificant changes were detected in ascitic fluid
      concentrations of antiinflammatory molecules. Thus, elevated levels of
      antiinflammatory compounds both in noninfected cirrhotic patients and in patients
      with SBP suggest a regulatory control of the inflammatory process by these
      molecules in liver cirrhosis patients.

PMID- 11508667
TI  - Serum HCV RNA levels correlate with histological liver damage and concur with
      steatosis in progression of chronic hepatitis C.
AB  - The role of HCV RNA levels and host factors in the severity of liver injury was
      studied. Enrolled were 298 consecutive liver biopsy-proven chronic hepatitis (CH)
      C patients (179 men; median age: 52 years, range 19-68; CH, 198; cirrhosis, 100)
      and 18 chronic hepatitis C with normal ALT. HCV genotypes were: 1a, 4.3%; 1b,
      53%; 2a/c, 28%; 3a, 7%; 4, 1.3%, and mixed 6.4%. Serum HCV RNA levels were
      similar for all genotypes (median: 2.8 x 10(6) eq/ml; range <0.2-69). In patients
      with chronic hepatitis without cirrhosis, the serum HCV RNA levels reflected the
      grade of liver necroinflammatory activity (R = 0.45; P < 0.001) and the stage of
      fibrosis (R = 0.51; P < 0.001), regardless of age, gender, HCV genotype, hepatic
      steatosis, and hepatic iron overload. Patients with high serum HCV RNA levels (>
      or =3 x 10(6) eq/ml) had higher ALT values (P < 0.002) than those with lower HCV
      RNA levels. Patients with normal ALT showed low HCV RNA levels (median: 0.82 x
      10(6) eq/ml) and histological features of minimal or mild chronic hepatitis.
      Cirrhotic patients showed significantly lower levels of viremia than those with
      chronic hepatitis with a similar HAI. The data of a subgroup of 62 patients with
      an established time of infection showed that for a similar duration of disease,
      patients with serum HCV RNA levels > or =3 x 10(6) eq/ml had a significantly
      higher fibrosis score than those with lower levels. HAI and fibrosis score were
      significantly higher in patients with HCV RNA levels > or =3 x 10(6) eq/ml and
      grade 3-4 steatosis than those with lower HCV RNA levels and steatosis grades.
      The data indicate that the liver damage is correlated with the HCV RNA levels and
      that a high viral load acts together with steatosis in accelerating the
      progression of liver injury.

PMID- 11508668
TI  - Alpha-interferon improves liver fibrosis in chronic hepatitis C: clinical
      significance of the serum N-terminal propeptide of procollagen type III.
AB  - Our objective was to estimate the effect of interferon (IFN) on the evolution of
      fibrosis in chronic hepatitis C and the significance of the N-terminal propeptide
      of procollagen type III (PIIIP) as a marker of fibrogenesis. One hundred
      seventeen patients, 72 male (61%) and 45 female (39%), with a mean age of 40.7+/
      11.9 years were treated with a2b-IFN, 3 to 5 MU, for 12 months: sustained
      responders (SR = 44), relapsers (RR = 35), and nonresponders (NR = 38). Liver
      biopsies were performed before treatment and 1 year after cessation of IFN for
      evaluation of the histological activity index (HAI). Serum PIIIP was obtained at
      the time of liver biopsy, at the beginning, during, and end of therapy and during
      the follow-up. The normal value in 29 healthy individuals was 0.37+/-0.18 U/L.
      Staging was reduced in 58% of SR, 12.5% of RR, and 11.5% of NR. There was a
      correlation between PIIIP and the HAI before (n = 71, r(s) = 0.41, P < 0.0004)
      and after IFN (n = 71, r(s) = 0.58, P < 0.0001). The SR had a better improvement
      in grading (90.3%; P < 0.05) and staging (58%; P < 0.001). The correlation of the
      HAI parameters with the variation of PIIIP showed significance only for fibrosis
      (r(s) = 0.36, P < 0.002) and portal inflammation (r(s) = 0.35, P < 0.01). PIIIP
      normalized only in patients whose fibrosis improved (P < 0.01). At the end of
      therapy, PIIIP had a predictive value in the distinction of SR from RR (PPV, 64;
      PNV, 55.6). During the follow-up, PIIIP remained lower in SR compared with RR and
      NR (P < 0.002). The response to a-IFN improved liver inflammation and fibrosis.
      Serum PIIIP is a useful noninvasive method to evaluate serially fibrogenesis in
      chronic hepatitis C treated with IFN.

PMID- 11508669
TI  - Low gastric toxicity of nitric oxide-releasing aspirin, NCX-4016, in rats with
      cirrhosis and arthritis.
AB  - The gastric toxic effects of aspirin (ASA) and NCX-4016, a nitric oxide (NO)
      releasing ASA, were compared in normal, cirrhotic, and arthritic rats. Oral
      administration of ASA (100 mg/kg) produced hemorrhagic lesions on the gastric
      mucosa in normal rats. The gastric ulcerogenic response to ASA was significantly
      worsened in both cirrhotic rats induced by N-nitrosodiethylamine and in arthritic
      rats induced by Freund's complete adjuvant. By contrast, NCX-4016 at 190 mg/kg (a
      dose equimolar to 100 mg/kg of ASA) did not induce damage in normal rat stomachs
      but caused slight lesions in the gastric mucosa of both cirrhotic and arthritic
      rats. Plasma salicylate levels following administration of ASA or NCX-4016 were
      not different between normal, cirrhotic, and arthritic rats, although the latter
      drug gave significantly lower values in any group of rats as compared to the
      former. Acid secretion was significantly increased in both cirrhotic and
      arthritic rats. ASA with 150 mM HCl caused severe gastric lesions in normal rats,
      the degree of damage being significantly greater than that induced by ASA alone.
      Coadministration of NOR-3, a NO donor, significantly prevented the development of
      gastric lesions induced by ASA, irrespective of whether or not ASA was given
      together with HCl. Gastric mucosal application of ASA (100 mg/kg) for 30 min
      caused a marked reduction of transmucosal potential difference (PD) with a
      minimal effect on gastric mucosal blood flow in both normal and cirrhotic rats,
      while that of NCX-4016 did not cause a PD reduction and produced a marked
      increase in the mucosal blood flow in both groups of rats. These results suggest
      that gastric mucosal susceptibility to ASA-induced damage is increased in both
      cirrhotic and arthritic rats (the process being partly accounted for by acid
      hypersecretion in these animals), NCX-4016 has even less gastric toxicity in both
      cirrhotic and arthritic rats, and the gastric-sparing effect of NCX-4016 is due,
      at least partly, to an increase of gastric mucosal blood flow, mediated by NO
      released from this drug.

PMID- 11508670
TI  - A fulminant hepatic failure model in the rat: involvement of interleukin-1beta
      and tumor necrosis factor-alpha.
AB  - The development of a fulminant hepatic failure (FHF) model is necessary for
      evaluating the efficacy of extracorporeal liver support systems. Recognizing the
      multifaceted functions of the liver, including synthesis and degradation, we
      investigated blood chemistry, histological findings, and survival rate in D
      galactosamine (GalN)-intoxicated rats. The pathophysiologic response of
      inflammatory cytokines, interleukin-1beta (IL-1beta) and tumor necrosis factor
      alpha (TNF-alpha), was also measured. Sprague-Dawley rats (200-300 g) were
      divided into two groups: GalN and saline injection. Rats were killed at 1, 3, 6,
      12, 24, 36, 48, 72, and 168 hr after intraperitoneal injection of GalN (1.4 g/kg)
      or saline. In both groups, liver-specific markers, liver histology, and IL-1beta
      and TNF-alpha levels in blood and liver tissue were analyzed. In a second series
      of experiments, the survival rates were examined after two administrations of
      GalN at 1.0, 1.4 or 2.0 g/kg, at a 12-hr interval. In the GalN injection group,
      the liver-specific markers reached peak levels between 36 and 48 hr after
      injection. Histologically, hepatocellular necrosis was seen at 6-48 hr, followed
      by a regenerative phase occurring between 72 and 168 hr. IL-1beta and TNF-alpha
      levels in liver tissue peaked at 12 hr and 1 hr, respectively. The levels of
      these cytokines in blood, however, did not change significantly. The survival
      rates at day 7 for 1.0, 1.4 or 2.0 g/kg GalN injected twice were 77.8%, 16.7%,
      and 0%, respectively. These results suggest that single and double injection of
      GalN enable the development of reversible and irreversible FHF models. The
      results also indicate that IL-1beta and TNF-alpha are useful markers of liver
      injury.

PMID- 11508671
TI  - Clinical significance of elevated alpha-fetoprotein in adults and children.
AB  - The aim of the current study is to identify underlying pathology associated with
      elevated serum alpha-fetoprotein (AFP; >20 ng/ml) among patients referred to a
      tertiary-care academic medical center with emphasis in liver diseases,
      hepatobiliary surgery, and liver transplantation. From May 1992 to April 1997,
      386 patients (320 adults and 66 children) with elevated AFP (>20 ng/ml) were
      identified from the Medical Archival System (MARS) database at the University of
      Pittsburgh Medical Center. The medical records from all these patients were
      retrospectively reviewed. Radiological, pathological, and biochemical profiles
      were obtained at the time of documented elevated AFP. These patients included:
      218 adults with malignancies, 102 adults without malignancies, 18 children and
      infants with malignancies, and 48 children and infants without malignancies.
      Thirty-two percent of adults were found to have raised AFP with liver disease and
      without hepatocellular carcinoma and 78% had some type of malignancy,
      predominantly hepatocellular carcinoma. Seventy-three percent of infants and
      children had elevated AFP without malignancy. Based on our findings, we recommend
      that all patients (adults, infants and children) with raised AFP of >20 ng/ml
      should undergo thorough evaluation to rule out malignant disease.

PMID- 11508672
TI  - Terbinafine-induced hepatitis and pancytopenia.

PMID- 11508673
TI  - Effects of current cigarette smoking on clinical course of Crohn's disease and
      ulcerative colitis.
AB  - Cigarette smoking worsens Crohn's disease (CD) but ameliorates ulcerative colitis
      (UC). In Israel, where there is no epidemiological association of smoking with
      CD, we examined the effects of current smoking on the course of CD and UC.
      Patients at nine public hospitals completed a questionnaire detailing their
      smoking history, disease course and treatments; subjects altering their smoking
      habit after the onset of disease were excluded. Sixty-four smokers and 144
      nonsmokers had CD, and 34 smokers and 158 nonsmokers had UC. No differences were
      found between CD smokers and nonsmokers for hospitalizations, operations, and
      requirement for corticosteroid and immunosuppressive treatment. By contrast, UC
      smokers had less extensive disease than nonsmokers (P < 0.02) and fewer
      hospitalizations (P = 0.01) and operations (P = 0.025). Our results agree with a
      minority of studies showing no adverse effect of smoking on the course of CD, and
      confirm the protective effect of smoking in UC.

PMID- 11508674
TI  - Hydrogen sulfide and colonic epithelial metabolism: implications for ulcerative
      colitis.
AB  - Hydrogen sulfide (HS-) impairs the oxidation of butyrate in colonocytes and is
      found in excess in feces of patients with ulcerative colitis. The possible
      pathogenic role of HS- in ulcerative colitis was further investigated. To
      investigate the metabolic effect of free and bound fecal HS-, isolated rat
      colonocytes were incubated in the presence of butyrate without and with the
      addition of (1) HS- in water, (2) sterile filtrates of fecal homogenates
      supplemented and incubated with HS- and known sources of fecal HS- production,
      and (3) HS- incubated with fecal agents known to bind HS-. Oxidation rates were
      obtained by quantifying the production of CO2. Total and free HS-, as well as the
      fecal ability to bind HS-, were determined in health and ulcerative colitis.
      Compared to the production of CO2 by colonocytes incubated with 2 mmol/liter of
      butyrate, the further addition of 1.25 and 2.5 mmol/liter of HS- in water reduced
      the production of CO2 by 57.6+/-10.0 and 98.9+/-1.4%, respectively. However, when
      adding fecal filtrate of homogenate supplemented with HS- corresponding to 1.25
      and 2.5 mmol/liter of HS- in water, the reduction of CO2 production was only
      30.7+/-12.0 and 53.2+/-14.0%, respectively. Neither the fecal level of total or
      free HS- nor the remarkable fecal ability to bind HS- differed in health or
      quiescent and active ulcerative colitis. Bound HS- had no or little effect on CO2
      production. Addition of fecal filtrate of nonsupplemented homogenate to
      colonocytes significantly reduced the oxidation of butyrate to CO2 about 25%,
      which could not be ascribed to fecal HS-. In conclusion, fecal HS- has little
      effect on butyrate oxidation in colonocytes and does not seem to play a
      pathogenic role for UC by impairing colonic epithelial metabolism. Other fecal
      agents seem to be more potent metabolic inhibitors than fecal HS-. The role of
      colonic contents in the pathogenesis of ulcerative colitis remains
      circumstantial.

PMID- 11508675
TI  - Successful treatment of refractory esophageal Crohn's disease with infliximab.

PMID- 11508676
TI  - Crohn's disease involving the lung: resolution with infliximab.

PMID- 11508677
TI  - EGF and TGF stimulate proabsorption of glucose and electrolytes by Na+/glucose
      cotransporter in awake canine model.
AB  - Growth factor-stimulated intestinal absorption has recently been described, but
      the cellular transport mechanisms mediating this response are unknown. The
      purposes of this study were to examine the effect that intraluminal and systemic
      EGF and TGF have in intestinal absorption, elucidate a possible mechanism through
      which they exert their activity, and compare this response to that of a mixed
      meal only. Jejunal and ileal Thiry-Vella intestinal segments were constructed in
      six dogs. Absorption was measured by infusing the loops with a physiological
      electrolyte solution containing either 10 mmol or 50 mmol glucose and [14C]PEG as
      the impermeant marker. In vivo studies show that the addition of either EGF or
      TGF resulted in increased absorption of Na+, Cl-, H2O, and glucose in the
      intestine. This response was significantly greater than that seen when giving a
      mixed meal alone. Luminal phloridzin, an inhibitor of the SGLT-1 transporter,
      inhibited intestinal absorption observed in response to EGF and TGF. In
      conclusion, these results suggest that growth factors are capable of up
      regulating intestinal absorption of electrolytes and nutrients and, these effects
      are mediated, at least in part, by SGLT-1 pathways.

PMID- 11508678
TI  - A spontaneous nitric oxide donor ameliorates small bowel ischemia-reperfusion
      injury in dogs.
AB  - Nitric oxide (NO) appears to play an important role in tissue injury during
      reperfusion. FK409 is the first spontaneous NO donor that increases plasma
      guanosine 3',5'-cyclic monophosphate. We investigated the effects of the NO donor
      FK409 (FK) on ischemia-reperfusion injury in a canine warm ischemia model.
      Fourteen adult mongrel dogs were divided into two groups: the control group and
      the FK group, which received FK. The superior mesenteric artery and vein were
      both clamped for 2 h and then reperfused for 12 h. Arterial and intramucosal pH
      were well maintained in the FK group in comparison with the control group.
      Histologically, ischemia-reperfusion injury was significantly more severe in the
      control group than in the FK group. The serum NO levels were significantly higher
      in the FK group than in the control group during FK administration. FK409 has
      protective effects on ischemia-reperfusion injury of the small intestine due to
      NO release.

PMID- 11508679
TI  - Coordinated Muc2 and Muc3 mucin gene expression in Trichinella spiralis infection
      in wild-type and cytokine-deficient mice.
AB  - Mucin hypersecretion is an important component of the immune response to
      gastrointestinal nematode infection. Two discrete types of mucin proteins exist
      in the mouse intestine, secretory Muc2 and membrane-bound Muc3. We examined Muc2
      and Muc3 expression in wild-type mice and mice lacking gamma interferon receptor
      (IFNgammaR-/-), tumor necrosis factor receptor 1 (TNFR1-/-) and interleukin 4
      (IL4-/-) infected with Trichinella spiralis. Infected wild-type mice demonstrated
      significant goblet cell hyperplasia and increased mucin glycoprotein. In situ
      hybridization showed this was accompanied by increases in Muc2 and Muc3 mRNA.
      Total intestinal mucin protein and Muc2 and Muc3 mRNA levels were also
      significantly increased in cytokine-deficient mice. These data demonstrate the
      coordinated up-regulation of two types of mucin genes in response to T. spiralis
      infection and may form the basis of an innate mucosal response independent of IFN
      gamma, TNF, and IL-4.

PMID- 11508680
TI  - Dynamic involvement of the inducible type of nitric oxide synthase in acid
      induced duodenal mucosal alkaline secretion in the rat.
AB  - It has previously been shown that mucosal nitric oxide synthase (NOS) is involved
      in acid-induced duodenal mucosal alkaline secretion. The primary aim of the
      present study was to elucidate which isoform of NOS is responsible in rats.
      Immunohistochemistry showed that inducible NOS (iNOS) was constitutively
      expressed in villous epithelial cells. Exposing the duodenal mucosa to 10 mM HCl
      resulted in an increased duodenal mucosal alkaline secretion. This response was
      totally inhibited by intraluminal administration of a selective inhibitor of iNOS
      (L-N6-1-iminoethyl-lysine). One hour after the acid exposure, western blot
      technique showed a marked increase in mucosal iNOS expression. A second acid
      exposure resulted in a further stimulation of alkaline secretion. These data
      suggest that exposure of the duodenal mucosa to HCI initiates an increased
      mucosal alkaline secretion, via NO synthesis mediated by iNOS located in the
      epithelial cells of the villi. In addition, luminal acid stimulates expression of
      iNOS.

PMID- 11508681
TI  - Clinical significance of oral urease in diagnosis of Helicobacter pylori
      infection by [13C]urea breath test.
AB  - This study was performed to evaluate the effect of oral flora on [13C]urea breath
      test in detecting H. pylori infection and find an optimal method and timing for
      sample collection. Forty-five volunteers were included in this study. The
      [13C]urea breath test was performed using mouthwash, endoscopic administration,
      and conventional methods. According to the receiver-operating characteristic
      curves, the earliest optimal time for discriminating H. pylori-positive and H.
      pylori-negative patients was at 25 min with the mouthwash method with 78%
      sensitivity and 82% specificity, at 2 min with the endoscopic administration
      method with 100% sensitivity and 100% specificity, and at 6 min with the
      conventional method with 100% sensitivity and 95% specificity. The study shows a
      significant effect of oral urease on the results of the [13C]urea breath test.
      The timing of sampling collection can be shortened to 6 min with the conventional
      method or to 2 min through endoscopic administration.

PMID- 11508682
TI  - Bile acid reflux and possible inhibition of Helicobacter pylori infection in
      subjects without gastric surgery.
AB  - Bile acids are generally known to inhibit growth of Helicobacter pylori in vitro,
      but whether they do so in humans with no gastric surgery has been uncertain. The
      present study addresses this issue. Among healthy control subjects with preserved
      acid secretion, H. pylori-positive subjects were older and had lower gastric bile
      acid concentrations than H. pylori-negative subjects (P < 0.05). Among gastric
      ulcer patients with preserved acid secretion, H. pylori-positive patients had a
      higher basal acid output than H. pylori-negative patients (P < 0.05). Among H.
      pylori-positive subjects with preserved acid secretion, duodenal ulcer patients
      had a higher basal and maximum acid output than healthy control subjects (P <
      0.01). In conclusion, gastric bile acids may suppress initial stages of H. pylori
      infection in subjects without gastric surgery. However gastric bile acids may
      have little effect on peptic ulcer disease, once H. pylori infection is
      established.

PMID- 11508683
TI  - Coexistence of eosinophilic gastroenteritis and Helicobacter pylori gastritis:
      causality versus coincidence.

PMID- 11508684
TI  - Use of montelukast as steroid-sparing agent for recurrent eosinophilic
      gastroenteritis.
AB  - Patients with eosinophilic gastroenteritis generally respond well to
      corticosteroids but relapses are common. Patients with relapsing disease are
      usually placed on long-term low-dose prednisone or immunosuppressive therapy.
      Here we reported on a patient with severe steroid-dependent eosinophilic
      gastroenteritis who was able to successfully taper off steroids and maintain
      remission after starting montelukast, a leukotriene receptor antagonist. To our
      knowledge, this is the first use of montelukast as a steroid sparing agent for
      eosinophilic gastroenteritis.

PMID- 11508685
TI  - Comparison of quality of life and nutritional parameters after total gastrectomy
      and a new type of pouch construction with simple Roux-en-Y reconstruction:
      preliminary results of a prospective, randomized, controlled study.
AB  - The aim of the study was to introduce a new type of gastric substitute, the
      aboral pouch, after total gastrectomy and to compare nutritional, motility, and
      quality of life parameters of patients with an aboral pouch to those undergoing
      simple Roux-en-Y reconstruction in a prospective, randomized, and controlled
      trial. To date 40 patients have entered the study. In 22 of them the aboral pouch
      was created; the remaining 18 patients with simple Roux-en-Y reconstruction
      served as the control group. Laboratory measurements, passage studies, lipid and
      carbohydrate absorption tests, and quality of life interviews were carried out as
      follow-up examinations. Preliminary results suggest that the aboral pouch has
      some advantages over simple Roux-en-Y reconstruction. Serum immunoglobulin M
      level and the quality of life estimated by the gastrointestinal quality of life
      index, yielded significantly better results in the pouch group.

PMID- 11508686
TI  - Protective effect of amtolmetin guacyl versus placebo diclofenac and misoprostol
      in healthy volunteers evaluated as gastric electrical activity in alcohol-induced
      stomach damage.
AB  - Amtolmetin guacyl (AMG) is a nonsteroidal antiinflammatory drug (NSAID) of high
      therapeutic activity and free of damaging effects on the gastrointestinal tract.
      Since acute ulcer and nausea have been found to be associated with gastric
      dysrhythmias, cutaneous electrogastrography and ultrasonographic study of the
      gastric emptying time were performed simultaneously in 24 healthy volunteers
      before and for 180 min after a liquid meal with 0.5 g/kg body weight of alcohol
      in double-blind, placebo-controlled, crossover studies. Before the recording
      session, each subject had taken placebo, AMG, a standard NSAID, or a gastric
      protective drug for four days. Alcohol administration increased the tachygastria
      percentage while diclofenac, AMG, and misoprostol alone did not induce
      gastrointestinal symptoms and gastric dysrhythmias. As regards alcohol-induced
      gastric dysrhythmia, placebo and diclofenac showed a clear increase in
      tachygastria while AMG and misoprostol did not. AMG is able to induce a
      normalization of gastric dysrhythmia induced by alcohol administration probably
      due to its peculiar mechanism of action, which involves capsaicin and CGRP
      pathways.

PMID- 11508687
TI  - Lack of gastric toxicity of nitric oxide-releasing indomethacin, NCX-530, in
      experimental animals.
AB  - The effects of a nitric oxide (NO) releasing derivative of indomethacin (NCX-530)
      on gastric ulcerogenic and healing responses were evaluated in rats and mice, in
      comparison with the parent compound indomethacin. Indomethacin (per os) produced
      damage in the rat stomach in a dose-dependent manner. NCX-530 (per os) itself,
      however, was not ulcerogenic and even showed a dose-dependent protection against
      HCl/ethanol-induced lesions in the rat stomach. Likewise, indomethacin given
      repeatedly delayed healing of gastric ulcers induced in mice by thermal
      cauterization, while NCX-530 did not affect the healing response and
      significantly promoted the healing as compared to indomethacin. These actions of
      NCX-530 were mimicked by the combined administration of a NO donor NOR-3 with
      indomethacin. The amount of NO metabolites was increased in both the gastric
      contents and serum when NCX-530, but not indomethacin, was given in pylorus
      ligated stomachs. Neither indomethacin nor NCX-530 influenced gastric acid
      secretion and transmucosal potential difference, yet NCX-530 caused a marked
      increase of gastric mucosal blood flow, which was preventable by carboxy-PTIO, a
      scavenger of NO. Gastric motility was increased by indomethacin but not by NCX
      530. In addition, NCX-530 inhibited PGE2 generation in both the intact and
      ulcerated gastric mucosa and showed antiinflammatory action on carrageenan
      induced rat paw edema, as effectively as indomethacin. These results suggest that
      unlike indomethacin, NCX-530 caused neither an irritating action on the stomach
      nor healing impairment effect on the preexisting gastric ulcers, but conferred
      gastric protection against HCl/ethanol, despite causing cyclooxygenase inhibition
      and antiinflammatory action, as effectively as indomethacin. This NO-releasing
      indomethacin, probably by releasing NO, exerts protective influences, such as an
      increase of gastric mucosal blood flow, that counteract the potential damaging
      effects of cyclooxygenase inhibition by indomethacin.

PMID- 11508688
TI  - Rickettsiaceae, rickettsia-like endosymbionts, and the origin of mitochondria.
AB  - Accumulating evolutionary data point to a monophyletic origin of mitochondria
      from the order Rickettsiales. This large group of obligate intracellular alpha
      Proteobacteria includes the family Rickettsiaceae and several rickettsia-like
      endosymbionts (RLEs). Detailed phylogenetic analysis of small subunit (SSU) rRNA
      and chaperonin 60 (Cpn60) sequences testify to polyphyly of the Rickettsiales,
      and consistently indicate a sisterhood of Rickettsiaceae and mitochondria that
      excludes RLEs. Thus RLEs are considered as the nearest extant relatives of an
      extinct last common ancestor of mitochondria and rickettsiae. Phylogenetic
      inferences prompt the following assumptions. (1) Mitochondrial origin has been
      predisposed by the long-term endosymbiotic relationship between rickettsia-like
      bacteria and proto-eukaryotes, in which many endosymbiont genes have been lost
      while some indispensable genes have been transferred to the host genome. (2) The
      obligate dependence of rickettsiae upon a eukaryotic host rests on the import of
      proteins encoded by these transferred genes. The nature of a proto-eukaryotic
      cell still remains elusive. The divergence of Rickettsiaceae and mitochondria
      based on Cpn60, and the evolutionary history of two aminoacyl-tRNA synthetases
      favor the hypothesis that it was a chimera created by fusion of an
      archaebacterium and a eubacterium not long before an endosymbiotic event. These
      and other, mostly biochemical data suggest that all the mitochondrion-related
      organelles, i.e., both aerobically and anaerobically respiring mitochondria and
      hydrogenosomes, have originated from the same RLE, while hydrogenosomal energy
      metabolism may have a separate origin resulting from a eubacterial fusion
      partner.

PMID- 11508689
TI  - Short-term effects of the 21-aminosteroid lazaroid tirilazad mesylate (PNU
      74006F) and the pyrrolopyrimidine lazaroid PNU-101033E on energy metabolism of
      human peripheral blood mononuclear cells.
AB  - Two groups of antioxidant compounds, the 21-aminosteroids and the
      pyrrolopyrimidines, have been found to act as neuroprotective drugs against lipid
      peroxidation in the injured CNS. Like glucocorticoids at high doses they are
      assumed to produce their effects at least in part by direct membrane stabilizing
      effects. In order to prove this hypothesis, we have investigated in this study
      the effects of these drugs on the energy metabolism of activated human peripheral
      blood mononuclear cells (PBMC) since these cells have been shown to serve as a
      suitable test system for substances affecting processes of ATP turnover. We
      compared the in vitro effects of (i) the 21-aminosteroid lazaroid tirilazad, (ii)
      the pyrrolopyrimidine lazaroid PNU-101033E and (iii) the glucocorticoid
      methylprednisolone on mitogen-induced respiration rate and ATP-consumption. We
      show that tirilazad inhibits concanavalin A-stimulated respiration rate and
      sodium cycling across the plasma membrane. The effect of methylprednisolone is
      similar indicating corresponding cellular mechanisms. However, unlike
      methylprednisolone, tirilazad produced no significant effect on calcium cycling
      across the plasma membrane. PNU-101033E in our test system caused cytotoxic
      effects on PBMC that did not allow us to quantify cellular actions on energy
      metabolism. Our results underline the view that tirilazad, first, is mimicking
      the high-dose immunosuppressive pharmacology of glucocorticoids such as
      methylprednisolone and, second, is likely to produce its therapeutic effects by
      direct physicochemical interactions with cellular membranes.

PMID- 11508690
TI  - Effect of garlic oil on the levels of various enzymes in the serum and tissue of
      streptozotocin diabetic rats.
AB  - Levels of red cell, serum acid, and alkaline phosphatases, serum amylase, alanine
      and aspartate transferase and bilirubin were examined in streptozotocin-induced
      diabetic rats treated with garlic oil and compared with the corresponding levels
      in diabetic control rats, normal rats and normal rats on garlic oil. Values of
      tissue amylase and total protein were also assessed from the pancreas, liver, and
      kidney. Treatment of diabetic rats with garlic oil significantly decreased the
      red cell phosphatase (p < 0.01), serum acid and alkaline phosphatase (p<0.001)
      when compared to diabetic control rats. Serum alanine and asparate transferases
      were significantly (p<0.001) decreased as well as serum amylase (p<0.002) in
      garlic oil treated diabetic rats as compared with diabetic control rats. When
      treated with garlic oil, however, diabetic and normal rats showed significant
      increase (p <0.05) in the amylase levels of the pancrease, liver, and kidney.

PMID- 11508691
TI  - p-Nitrophenylphosphatase activity catalyzed by plasma membrane (Ca(2+) +
      Mg(2+)ATPase: correlation with structural changes modulated by glycerol and
      Ca(2+).
AB  - The plasma membrane (Ca(2+) + Mg(2+))ATPase hydrolyzes pseudo-substrates such as
      p-nitrophenylphosphate. Except when calmodulin is present, Ca(2+) ions inhibit
      the p-nitrophenylphosphatase activity. In this report it is shown that, in the
      presence of glycerol, Ca(2+) strongly stimulates phosphatase activity in a dose
      dependent manner. The glycerol- and Ca(2+)-induced increase in activity is
      correlated with modifications in the spectral center of mass (average emission
      wavenumber) of the intrinsic fluorescence of the enzyme. It is concluded that the
      synergistic effect of glycerol and Ca(2+) is related to opposite long-term
      hydration effects on the substrate binding domain and the Ca(2+) binding domain.

PMID- 11508692
TI  - Quantitative analysis of phospholipid peroxidation and antioxidant protection in
      live human epidermal keratinocytes.
AB  - To characterize oxidative stress in phospholipids of normal human epidermal
      keratinocytes we metabolically labeled their membrane phospholipids with a
      natural oxidation-sensitive fluorescent fatty acid, cis-parinaric acid, and
      exposed the cells to two different sources of oxidants--a lipid-soluble azo
      initiator of peroxyl radicals, 2,2'-azobis(2,4-dimethyl-valeronitrile), AMVN, and
      a superoxide generator, xanthine oxidase/xanthine. We demonstrated that both
      oxidants induced pronounced oxidation of four major classes of cis-parinaric acid
      labeled phospholipids-phosphatidylcholine, phosphatidylethanolamine,
      phosphatidylserine, and phosphatidylinositol-in normal human epidermal
      keratinocytes that was not detectable as any significant change of their
      phospholipid composition. Vitamin E was effective in protecting the cells against
      phospholipid peroxidation. Since viability of normal human epidermal
      keratinocytes was not changed either by labeling or exposure to oxidants the
      labeling protocol and oxidative stress employed are compatible with the
      quantitative analysis of phospholipid peroxidation in viable cells.

PMID- 11508693
TI  - Decreased susceptibility of heart mitochondria from diabetic GK rats to
      mitochondrial permeability transition induced by calcium phosphate.
AB  - Type 2 diabetes (or non-insulin dependent diabetes mellitus, NIDDM) is a common
      metabolic disease in man. The Goto-Kakizaki (GK) rat has been designed as a NIDDM
      model. Previous studies with this strain have shown differences at the
      mitochondrial level. The mitochondrial permeability transition (MPT) is a widely
      studied phenomenon but yet poorly understood, that leads to mitochondrial
      dysfunction and cell death. The aim of this work was to compare the differences
      in susceptibility of induction of the MPT with calcium phosphate in GK and Wistar
      rats. Our results show that heart mitochondria from GK rats are less susceptible
      to the induction of MPT, and show a larger calcium accumulation before the
      overall loss of mitochondrial impermeability.

PMID- 11508694
TI  - Promoter characterization and expression of the gene coding for the human GM2
      activator protein.
AB  - Genomic clones of the human GM2 activator protein have been isolated and
      analyzed. The 5' region of the gene demonstrated promoter activity as ascertained
      by its ability to drive luciferase gene expression in transfected COS cells. This
      sequence contains GC rich region and several putative promoter elements were
      present, including Sp1, AP2, cAMP-responsive element, and B-cell-specific
      activating protein. Analysis of tissue distribution of the GM2 activator protein
      gene revealed tissue-specific variations in transcript levels. Placenta, bone
      marrow, mammary gland, bladder, lymph node, and spleen had the highest mRNA
      levels.

PMID- 11508695
TI  - Cross-Linking study of cytochrome P450 1A2 in proteoliposomes.
AB  - Proteoliposomes, containing cytochrome P450 1A2, were obtained by the cholate
      dialysis technique. The effect of bifunctional cross-linking reagents on the
      purified hexameric cytochrome P450 1A2 in an aqueous medium and on the
      proteoliposomal P450 1A2 have been compared. Electrophoretic analysis of the
      modified proteins demonstrated the same oligomeric (hexameric) organization of
      the hemoprotein in each case.

PMID- 11508696
TI  - Chenodeoxycholate is a potent inducer of the permeability transition pore in rat
      liver mitochondria.
AB  - Several reports support the concept that bile acids may be cytotoxic during
      cholestatic disease process by causing mitochondrial dysfunction. Here we report
      additional data and findings aimed at a better understanding of the involvement
      of the permeability transition pore (PTP) opening in bile acids toxicity. The
      mitochondrial PTP is implicated as a mediator of cell injury and death in many
      situations. In the presence of calcium and phosphate, chenodeoxycholic acid
      (CDCA) induced a permeability transition in freshly isolated rat liver
      mitochondria, characterized by membrane depolarization, release of matrix
      calcium, and osmotic swelling. All these events were blocked by cyclosporine A
      (CyA) and the calcium uniporter inhibitor ruthenium red (RR). The results suggest
      that CDCA increases the sensitivity of isolated mitochondria in vitro to the
      calcium-dependent induction of the PTP.

PMID- 11508697
TI  - Increase of membrane permeability of mitochondria isolated from water stress
      adapted potato cells.
AB  - In order to gain some insight into mitochondria permeability under water stress,
      intact coupled mitochondria were isolated from water stress adapted potato cells
      and investigations were made of certain transport processes including the
      succinate/malate and ADP/ATP exchanges, the plant mitochondrial ATP-sensitive
      potassium channel (PmitoKATP) and the plant uncoupling mitochondrial protein
      (PUMP). The Vmax values measured for succinate/malate and ADP/ATP carriers, as
      photometrically investigated, as well as the same values for the PmitoK(ATP) and
      the PUMP were found to increase; this suggested that mitochondria adaptation to
      water stress can cause an increase in the membrane permeability.

PMID- 11508698
TI  - Diadenosine tetraphosphate-gating of recombinant pancreatic ATP-sensitive K(+)
      channels.
AB  - Diadenosine tetraphosphate (Ap4A) has been recently discovered in the pancreatic
      beta cells where targets ATP-sensitive K(+) (K(ATP)) channels, depolarizes the
      cell membrane and induces insulin secretion. However, whether Ap4A inhibit
      pancreatic K(ATP) channels by targeting protein channel complex itself was
      unknown. Therefore, we coexpressed pancreatic K(ATP) channel subunits, Kir6.2 and
      SUR1, in COS-7 cells and examined the effect of Ap4A on the single channel
      behavior using the inside-out configuration of the patch-clamp technique. Ap4A
      inhibited channel opening in a concentration-dependent manner. Analysis of single
      channels demonstrated that Ap4A did not change intraburst kinetic behavior of
      K(ATP) channels, but rather decreased burst duration and increased between-burst
      duration. It is concluded that Ap4A antagonizes K(ATP) channel opening by
      targeting channel subunits themselves and by keeping channels longer in closed
      interburst states.

PMID- 11508699
TI  - Simultaneous determination of alpha-, gamma-tocopherol and their quinones in rats
      plasma and tissues using reversed-phase high-performance liquid chromatography.
AB  - We established a method to determine simultaneously alpha- and gamma-tocopherol (
      Toc) and their quinones (alpha-TQ and p-gamma-TQ) in biological samples by
      reverse-phase high-performance liquid chromatography (HPLC). Tocs had a shorter
      retention time than TQs, and alpha-forms had a shorter retention times than gamma
      forms. Four peaks of Tocs and TQs were completely separated by this method.
      Subsequently, we investigated the distribution of alpha-, gamma-Toc and TQ in rat
      tissues and the excretion of Tocs and TQs in rat bile by the above HPLC method.
      Rats deficient in vitamin E were divided into two groups, gamma-Toc group and
      alpha+ gamma-Toc group, and tissues were collected at 6 and 24 h after
      intravenous administration of Tocs. Also, bile collection was started immediately
      and performed at 3 h intervals during 24 h after intravenous administration. The
      concentration of alpha- and gamma-Toc and their quinones in plasma, tissues and
      bile were determined by this method. Gamma-Toc concentration in the liver of
      alpha+gamma-Toc group was higher than that of gamma-Toc group. However, p-gamma
      TQ in the liver was not significantly different between alpha+gamma-Toc group and
      gamma-Toc group. Also, both alpha-TQ and p-gamma-TQ were present in very low
      concentrations in all tissues. Therefore, we suggested that the distribution of
      gamma-Toc is affected by alpha-Toc present in vivo, but the oxidative production
      of p-gamma-TQ from gamma-Toc is not affected.

PMID- 11508700
TI  - Isolation, identification and biological activity of 24R,25-dihydroxy-3-epi
      vitamin D3: a novel metabolite of 24R,25-dihydroxyvitamin D3 produced in rat
      osteosarcoma cells (UMR 106).
AB  - We recently identified 1alpha,25-dihydroxy-3-epi-vitamin D3 [1alpha,25(OH)2-3-epi
      D3] as a metabolite of 1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3] produced
      in rat osteosarcoma cells (UMR 106). We now report the isolation of 24R,25
      dihydroxy-3-epi-vitamin D3 [24R,25(OH)2-3-epi-D3] as a metabolite of 24R,25
      dihydroxyvitamin D3 [24R,25(OH)2D3] by high-performance liquid chromatography
      (HPLC) with chiral column and its structure assignment by proton nuclear magnetic
      resonance (1H-NMR) and liquid chromatography-mass spectrometry (LC-MS) analysis.
      We also demonstrated the production of 24R,25(OH)2-3-epi-D, in two other cell
      lines [human colon carcinoma cells (Caco-2) and porcine kidney cells (LLC-PK1)]
      which were previously shown to convert 1alpha,25(OH)2D3 into 1alpha,25(OH)2-3-epi
      D3. It can be seen that the production of 24R,25(OH)2- 3-epi-D3 from
      24R,25(OH)2D3 is lower than that of 1alpha,25(OH)2-3-epi-D3 from 1alpha,25(OH)2D3
      in all the cells studied. 24R,25(OH)2-3-epi-D3 was found to be inactive in terms
      of its ability to bind to the vitamin D receptor (VDR), in inhibiting
      proliferation and in inducing differentiation of human promyelocytic leukemia
      cells (HL-60). Thus, our study indicates that the C-3 epimerization pathway is
      common to both 1alpha,25(OH)2D3 and 24R,25(OH)2D3 and may play an important role
      in modulating the concentration and the biological activity of these two major
      vitamin D3 metabolites in target tissues.

PMID- 11508702
TI  - Evaluation of body composition using dual-energy X-ray absorptiometry, skinfold
      thickness and bioelectrical impedance analysis in Japanese female college
      students.
AB  - We compared three methods for evaluating body composition: dual-energy X-ray
      absorptiometry (DXA), skinfold thickness (Skinfolds), and bioelectrical impedance
      analysis (BIA). Subjects were 155 healthy young college-aged Japanese females
      whose mean+/-SD (range) age, body height, body weight and body mass index (BMI)
      were 20.1+/-0.3 (19.6-21.1) y, 158.9+/-4.7 (145.4-172.6) cm, 52.0+/-6.8 (39.4
      84.6) kg and 20.6+/-2.3 (16.5-32.5), respectively. Their mean skinfold thickness
      at the triceps and subscapular were 16.9+/-4.7 (8.0-31.0) and 16.0+/-5.7 (7.0
      40.0) mm, respectively. Mean body fat mass percentages evaluated by DXA,
      Skinfolds and BIA were 29.6+/-5.1, 22.8+/- 5.3 and 25.8+/-4.7%, respectively.
      Body fat mass was 15.4+/-4.4, 12.1+/-4.5 and 13.6+/-4.5 kg, respectively. Simple
      correlation coefficients between the three methods for body fat mass percentages
      provided the following coefficients: r=0.741 for DXA vs. Skinfolds, r=0.792 for
      DXA vs. BIA and r=0.781 for Skinfolds vs. BIA. Simple correlation coefficients
      for body fat mass were as follows: r=0.898 for DXA vs. Skinfolds, r=0.927 for DXA
      vs. BIA and r=0.910 for Skinfolds vs. BIA (all p<0.001). There were significant
      differences in the values among the three methods with the Skinfolds providing
      the lowest body fat mass and percentage, and DXA the highest (p<0.001). They all
      appear to be strongly correlated for evaluating body composition: however,
      different cut-off values for defining obese and lean need to be defined for each
      method.

PMID- 11508701
TI  - Effect of exercise on the metabolism of vitamin B6 and some PLP-dependent enzymes
      in young rats fed a restricted vitamin B6 diet.
AB  - The effect of exercise on vitamin B6 metabolism and PLP-dependent enzymes was
      studied in rats fed a diet with or without vitamin B6. Metabolism of some amino
      acids (citrulline, arginine, ornithine and threonine) inhibited in the B6
      deficient rats was normalized during exercise. Exercise was also effective in
      storing vitamin B6 in the body by lowering excretion of vitamin B6, when intake
      of vitamin B6 was restricted. Aspartatae aminotransferase activity was higher in
      the red portion of the gastrocnemius muscle than that of the white one, whereas
      glycogen phosphorylase activity was vice versa and furthermore glycogen content
      in the white portion was very low in the vitamin B6-deficient rat. From the data
      obtained, it has been suggested that the red and white portions of the
      gastrocnemius muscle seemed to be more important in metabolizing amino acids and
      hydrolyze glycogen, respectively.

PMID- 11508703
TI  - Acute toxicity and mutagenicity study on branched corn syrup and evaluation of
      its laxative effect in humans.
AB  - We developed a branched corn syrup (BCS, average molecular weight: 500, content
      of indigestible portion: 45%) by heat treatment of indigestible dextrin with
      hydrochloric acid. To confirm the safety of BCS, we conducted both an acute
      toxicity test and a mutagenicity test. Moreover, we observed gastroenteric
      effects of BCS in fifty healthy humans. The results are summarized as follows. 1)
      There was no death observed after oral administration of BCS in Sprague-Dawley
      strain rats. Lethal dose (LD)50, value was estimated to be more than 10 g/kg body
      weight. 2) No mutagenicity was observed in Salmonella typhimurium TA98, TA100,
      TA1535, TA1537, or Escherichia coli WP2uvrA. 3) Fifty adults were divided into
      five groups often (five of each sex) and orally administered BCS at 0.2, 0.3,
      0.4. 0.5 and 0.6 g/kg body weight as indigestible portion. Although no diarrhea
      was observed in females, BCS at 0.6 g/kg as indigestible portion caused diarrhea
      in two out of five males. The maximum non-effective dose of indigestible portion
      of BCS was estimated to be 0.5 g/kg in males and more than 0.6 g/kg in females.

PMID- 11508704
TI  - Expression and properties of human liver beta-ureidopropionase.
AB  - A cDNA encoding beta-ureidopropionase (BUP) was isolated from a human liver cDNA
      library, expressed in E. coli, and purified from the culture extract. The 2,006
      bp cDNA contained a 1,152 bp open reading frame encoding a protein of 384 amino
      acids with a molecular weight of 43,165 Da. The subunit molecular weight of the
      enzyme expressed was about 43,000 Da. The enzyme was inhibited by 1 mM
      propionate, but not by 10 mM beta-alanine. Chemical analysis of the purified
      human BUP showed 0.54 zinc atoms per subunit, and the sequence of BUP cDNA
      contained one putative zinc-binding site motif. The purified enzyme had a pI of
      5.65, and exhibited positive cooperativity with N-carbamoyl-beta-alanine as the
      substrate with a Hill coefficient 2.0. These properties of human BUP, except the
      inhibition by beta-alanine, were similar to the rat liver purified enzyme. Beta
      alanine inhibits rats BUP activity. The complex regulatory function and the
      negative cooperative mechanism of BUP by beta-alanine have been observed in rats.
      This kind of mechanism may not exist in humans, because beta-alanine did not
      inhibit human BUP.

PMID- 11508705
TI  - Caffeine as a lipolytic food component increases endurance performance in rats
      and athletes.
AB  - Caffeine is one of the famous ergogenic aids in the athletic field. Caffeine has
      been known to stimulate lipolysis that spares stored glycogen utilization during
      moderate intensity exercise. Therefore, we investigated the effects of caffeine
      ingestion on exercise performance in rats and athletes. Rats were administered
      the caffeine (6 mg/kg) 1 h prior to the exercise then were run on a treadmill at
      a speed of 20 m/min. They were decapitated at 0 min, 30 min, 60 min of exercise,
      and exhausted time point. Human subjects ingested the caffeine (5 mg/kg) 1 h
      prior to the exercise. They exercised on a cycle ergometer at 60% of their VO2max
      for 45 min, and then the exercise intensity was increased to 80% of their VO2max
      until exhaustion. Blood and breathing gas samples were collected and calculated
      every 10 min during exercise. Respiratory exchange ratio of the caffeine trial
      was significantly lower than that of the placebo trial in the athletes' study
      (p<0.05). Blood free fatty acid (FFA) levels in studies of both rats and athletes
      were increased by caffeine ingestion during exercise (p<0.05). Blood lactate
      levels were also increased during exercise in both rats and athletes (p<0.05).
      Increased FFA and glycerol concentrations reduced glycogen utilization during
      exercise compared with placebo group in rats. In addition, endurance time to
      exhaustion was significantly increased by the caffeine ingestion in both rats and
      athletes (p<0.05). These results suggest that the caffeine ingestion enhanced
      endurance performance resulting from spare stored glycogen with increasing
      lipolysis from adipose tissues and fat oxidation during exercise both in rats and
      in athletes.

PMID- 11508706
TI  - Blood pressure, serum cholesterol concentration and their related factors in
      urban and rural elderly of Ho Chi Minh City.
AB  - In Vietnam, information about blood pressure, serum lipids and their factors is
      limited. To obtain some of this information, a cross sectional nutrition survey
      was carried out in an urban and rural area of Ho Chi Minh City with 217
      participants aged 60-69 y (148 females and 69 males). Anthropometry and blood
      pressure were measured. For three consecutive weekdays, 24 h dietary recalls were
      performed. Single 24 h urine was collected for sodium and potassium analysis. A
      fasting blood sample was taken and biochemical parameters were measured. Results
      indicate a high percentage of hypertension in urban (female: 35.5%, male: 43.8%)
      and rural areas (female: 22.2%, male: 35.1%). Blood pressure was correlated with
      body mass index (BMI) and 24 h urinary sodium-to-potassium (Na/K) ratio. A high
      prevalence of serum total cholesterol (TC) above 220 mg/dL (female: 55.3%, male:
      31.3%) and overweight (female: 34.2%, male: 25.0%) were observed in urban
      residents. By contrast, 5.6% and 24.3% of rural females and males respectively
      had TC below 150 mg/dL and both genders had the same prevalence of underweight
      (32.4%). TC was positively correlated with body weight, BMI, dietary protein and
      dietary lipids. Overweight might be a major risk factor for hypertension in our
      urban elderly. A high Na/K intake ratio might be a risk factor for hypertension
      in both areas. The high prevalence of elevated TC in the urban area might to be
      related to the high lipid intake, and the high prevalence of low TC in the rural
      area might to be related to the low lipid intake.

PMID- 11508707
TI  - Analysis of rhythmical jaw movements produced by taste stimulation in rats.
AB  - Taste stimulation of the mouth induces various oral movements. Sucrose or salt
      solution induces rhythmical jaw movements (RJM) or tongue protrusion as an
      ingestive behavior. Bitter taste induces a gaping or tongue retraction as an
      aversive behavior. There is no report that describes the precise pattern of jaw
      movements induced by taste stimulation. The purpose of the present study is to
      clarify the pattern of the taste-induced RJM with electromyographic activities of
      the masticatory muscles in the anesthetized rat. When water was injected into the
      mouth of the rat, an RJM was induced. In this type of RJM, the lower jaw swung
      right and left side in each open-close cycle alternately. The anterior digastric
      muscle was active in every opening phase, while activities of the jaw closing
      muscles were generally weak. The RJM induced by water was opening-dominant
      movements. Sucrose or salt solution induced a similar pattern of RJM to water
      induced RJM. When acetic acid was injected, amplitude of the alternate lateral
      jaw movement was significantly larger than that in the water-induced RJM. The
      activity of the superficial temporalis muscle was large in those closing phases
      with ipsilateral side movement, while it was small in the closing phases with
      contralateral movement. The pattern of quinine-induced RJM was characterized by
      small lateral, large open-close and large antero-posterior movements. Tastes
      which are reported to induce ingestive behavior such as sweet or salty don't
      alter the pattern of RJM; however, the tastes which induce aversive behavior make
      the pattern of RJM different from the water-induced RJM.

PMID- 11508708
TI  - Behavioral taste similarities and differences among monosodium L-glutamate and
      glutamate receptor agonists in C57BL mice.
AB  - Monosodium L-glutamate (MSG) and 5'-ribonucleotides elicit umami taste in humans
      and probably in some species of animals. Previous studies suggest that taste
      mGluR4 and NMDA receptor may be involved in taste transduction for umami, but
      behavioral responses in rats do not support the involvement of NMDA receptor. In
      the present study, behavioral similarities and differences among MSG, mGluR4
      agonist L(+)-2-amino-4-phosphonobutyrate (L-AP4), and NMDA receptor agonist N
      methyl-D-aspartate (NMDA) were compared in C57BL mice by using a conditioned
      taste aversion paradigm. Mice conditioned to avoid either MSG or 10 mM L-AP4
      appeared to avoid MSG, disodium 5'-inosinate (IMP), a mixture of MSG and IMP, and
      L-AP4, but not NMDA. Aversive conditioning to either sucrose or NMDA was
      generalized only to a mixture of MSG+IMP or NaCl. However, aversive conditioning
      to L-AP4 at 1 mM was generalized to NMDA and the umami substances. Lick rates for
      L-AP4 increased by mixing with (RS)-alpha-cycloprophy-4-phosphonophenylglycine
      (mGluR4 antagonist) when animals were conditioned to avoid MSG or L-AP4. Lick
      rates for NMDA also either decreased or increased by mixing with glycine (NMDA
      receptor coagonist) or D(-)-2-amino-5-phosphonopentanoic acid (NMDA receptor
      antagonist) when animals were conditioned to avoid L-AP4 or NMDA. In sucrose
      conditioned mice. gurmarin (a sweet inhibiting peptide) suppressed the avoidance
      of sucrose and a mixture of MSG and IMP, but not L-AP4 and NMDA. The results
      suggest the possibility that to C 57BL mice MSG may taste similar to L-AP4 but
      different from NMDA, although both types of glutamate receptors as well as
      gurmarin-sensitive sweet receptor may be involved in perception of umami taste.

PMID- 11508709
TI  - 1,1-Diphenyl-2-picrylhydrazyl radical-scavenging active compounds from greater
      cardamom (Amomum subulatum Roxb.).
AB  - Constituents of the fruits of greater cardamom (Amomum subulatum) were
      fractionated into three fractions, the dichloromethane extract, and the ethyl
      acetate-soluble and water-soluble fractions of the 70% aqueous acetone extract.
      The ethyl acetate-soluble fraction showed a high radical-scavenging activity
      against 1,1-diphenyl-2-picrylhydrazyl (DPPH). Four compounds were isolated from
      the ethyl acetate-soluble fraction, and their structures were ascribed to
      protocatechualdehyde (1), protocatechuic acid (2), 1,7-bis(3,4
      dihydroxyphenyl)hepta-4E,6E-dien-3-one (3) and 2,3,7-trihydroxy-5-(3,4-dihydroxy
      E-styryl)-6,7,8,9-tetrahydro-5H-benzocycloheptene (4) on the basis of
      spectroscopic evidence. This is the first isolation of these compounds from
      greater cardamom. In particular, 4 was a new type of cyclic diarylheptanoid. DPPH
      radical-scavenging activity of these compounds was measured by colorimetric
      analysis. Compounds 1 and 3 showed stronger activity than such natural
      antioxidants as alpha-tocopherol and L-ascorbic acid. Compounds 2 and 4 were
      comparable to alpha-tocopherol and L-ascorbic acid.

PMID- 11508710
TI  - Lactobacillus casei strain Shirota-fermented milk stimulates indigenous
      Lactobacilli in the pig intestine.
AB  - The aim of this study was to determine the effect of a probiotic, i.e. fermented
      milk prepared with Lactobacillus casei strain Shirota, on indigenous Lactobacilli
      in the pig large intestine. This fermented milk was given as a probiotic to
      experimental pigs for 2 weeks. The fecal organic acid concentration increased
      with the fermented milk; acetate and propionate increased significantly (p<0.05).
      At the same time, lactate and butyrate tended to increase. The fecal pH was
      significantly reduced by the fermented milk (p<0.05). Although the number of
      bacteria of strain Shirota in the intestinal contents was much smaller than those
      of indigenous Lactobacilli, 10(4) vs 10(8) (cfu/g), the numbers of indigenous
      Lactobacilli and Bifidobacteria in the pig intestine appeared to increase with
      the fermented milk. In addition, the phenotypic diversity (phenotypic group
      numbers) of indigenous Lactobacilli increased from 3 to 8 with the fermented milk
      supplementation. Thus the fermented milk affected the indigenous Lactobacillus
      population and constitution.

PMID- 11508711
TI  - Elevation of blood NAD level after moderate exercise in young women and mice.
AB  - We previously reported that the blood NAD levels are decreased by severe
      exercise, and administration of nicotinamide, a precursor of NAD, improves the
      endurance capacity of mice. In the present study, we determined whether moderate
      exercise changes the blood NAD levels in humans and mice. College female students
      exercised moderately with bike-ergometers. The blood NAD levels elevated after
      moderate exercise. Mice were forced to swim in a running water pool for 5 min as
      a moderate exercise, 15 min as a strong exercise, and until exhaustion as a
      severe exercise (average swimming time was 28.7 min). A 5 min swim gave a result
      similar to that of moderate exercise by human subjects. However, the blood NAD
      levels decreased after all-out exercise. The changes in whole blood tryptophan (a
      precursor of pyridine nucleotides) levels were similar to that in NAD. The
      glucose levels in whole blood and the non-esterified fatty acid levels in serum
      decreased according to exercising time. These data are the first demonstration of
      moderate exercise raising the blood NAD levels in human and mice. Elevation of
      the blood NAD levels may reflect changes in niacin metabolism that occur in
      response to exercise.

PMID- 11508712
TI  - Content of phylloquinone and menaquinone in the tissues of mummichog Fundulus
      heteroclitus fed diets containing different forms of vitamin K.
AB  - The contents of vitamin K in the plasma and tissues (kidney, liver and gonad) of
      mummichog Fundulus heteroclitus fed diets supplemented with different vitamin K
      groups were determined. The vitamin K mainly detected in the gastrointestinal
      tract of each experimental group was the one supplemented in the respective diet,
      and all other forms of vitamin K were observed at low concentrations. This
      implies that the main vitamin K source for mummichog is their food. Further
      evidence that the main vitamin K source is the food is that the elevation of
      vitamin K concentrations in the plasma and other tissues in this experiment was
      brought about by vitamin K added to the feed. The phylloquinone-rich diet raised
      the phylloquinone concentration in the plasma and the tissues much higher than
      the diets supplemented with short and/or long chain menaquinones. This indicates
      that phylloquinone is more easily accumulated into the body of fish than the
      menaquinone homologues. There were apparent differences in absorption and
      deposition of vitamin K between females and males. This may be a factor in the
      high mortality in male mummichog during the spawning season but further
      clarification of the causes of the mortality is required.

PMID- 11508713
TI  - Comparison of dihydrofolate reductase activities for folic acid in pigs and rats
      using in vivo and in vitro evaluation techniques.
AB  - The activity of dihydrofolate reductase (DHFR) for folic acid (PteGlu) was
      evaluated in pigs by in vivo and in vitro experiments. The results were compared
      with those of rats. Since bile secretion of reduced folates reflects the activity
      of DHFR for PteGlu in the body, the bile secretion rates of reduced folates
      including tetrahydrofolate (H4PteGlu), 5-methyltetrahydrofolate, 5,10
      methylenetetrahydrofolate, and 10-formyltetrahydrofolate were determined by using
      high-performance liquid chromatography with electrochemical detection, after the
      intravenous injection of PteGlu at 1 mg/kg body weight to pigs and rats. Although
      the PteGlu injection raised the total secretion rate of reduced folates. the
      total increased amount of reduced folates secreted into bile from 0 h to 2.5 h
      after PteGlu injection in pigs was about one-tenth of that in rats. The enzyme
      kinetics of DHFR for PteGlu was examined at the physiological condition (pH 7.4
      and 3 7 degrees C). Affinity chromatography was applied to liver homogenates of
      pigs and rats to obtain DHFR. The final product of the enzyme reaction, H4PteGlu,
      was measured. The Km for pig enzyme was similar to that for rat enzyme, whereas
      the Vmax for the pig enzyme was less than 1/5 of that for the rat's. The
      comparison of the ratio of Vmax to Km between pig and rat enzymes suggests that
      PteGlu is a much less efficient substrate for pig liver DHFR. In short, these
      results from in vivo and in vitro experiments suggest that the role of DHFR for
      PteGlu in pigs is physiologically much less important than that in rats.

PMID- 11508714
TI  - Awareness in classical differential eyeblink conditioning in young and aging
      humans.
AB  - The role of awareness and its impact on learning the conditioned eyeblink
      response was investigated in both trace and delay discrimination eyeblink
      conditioning in young and aging participants, in 4 paradigms: delay 750, delay
      1,250, trace 500, and trace 1,000. Participants concurrently watched a silent
      movie about which they were questioned afterward. Acquisition in both the trace
      and delay discrimination task was correlated with awareness of conditioning
      stimulus contingencies, regardless of age. Age-dependent deficits were observed
      in trace discrimination but not in delay discrimination, with more severe
      deficits appearing at the longer trace interval. The percentage of aware
      participants was also found to be greater in the young population than in the
      aging population. These results indicate that awareness or knowledge of stimulus
      contingencies may be an important contributor to successful acquisition in higher
      order discrimination tasks.

PMID- 11508715
TI  - Structure and irregularity in the spontaneous behavior of young infants.
AB  - Persistent, irregular fluctuations in spontaneous motor activity are common in
      the young of many vertebrate species, but whether the irregularity is intrinsic
      to the dynamics of motor activation or the result of random perturbations is not
      known. Analysis of the second-by-second variation in the general body movement of
      awake human infants 1 and 3 months after birth revealed low dimensional structure
      in the characteristically irregular motor activity and exponential rates of
      divergence of initially similar states of motor activation. Results support the
      conclusion that irregularity is an intrinsic property of the dynamics of motor
      activation involving relatively few effective degrees of freedom and raise
      questions about the advantages or disadvantages of irregularity built into early
      behavioral organization.

PMID- 11508716
TI  - Amygdala lesions block conditioned enhancement of the early component of the rat
      eyeblink reflex.
AB  - A tone conditioned stimulus (CS) previously paired with a grid shock
      unconditioned stimulus (US) can greatly enhance the early electromyographic (EMG)
      component (R1) of the rat eyeblink reflex. The hypothesis that the central
      nucleus of the amygdala (ACe) is an essential part of the circuitry mediating
      conditioned R1 enhancement was tested. After bilateral ACe lesions (L) or a sham
      operation (S), rats received paired presentations of the CS and US (P) or
      explicitly unpaired CS and US presentations (U), resulting in 4 groups: P/S, P/L,
      U/S, and U/L. ACe lesions completely prevented conditioned R1 enhancement, which
      was only exhibited in Group P/S. In the latter group, the "preextinction"
      conditioned enhancement effect was roughly a 2-fold increase in the R1 magnitude.
      Circuit-level mechanisms are discussed, and some advantages of the eyeblink EMG
      response in this general conditioning paradigm are considered.

PMID- 11508717
TI  - Perirhinal cortex and place-object conditional learning in the rat.
AB  - The present study examined whether excitotoxic lesions of the perirhinal cortex
      can affect acquisition of a place-object conditional task in which object and
      spatial information must be integrated. Testing was carried out in a double Y
      maze apparatus, in which rats learned a conditional rule of the type, "In Place
      X, choose Object A, not Object B (A+ vs. B-); in Place Y, choose Object B, not
      Object A (A- vs. B+)." Perirhinal cortex lesions significantly impaired
      acquisition of this task while sparing performance of an allocentric spatial
      memory task performed in a radial arm maze. Perirhinal cortex lesions also had no
      apparent effect on a 1-pair object discrimination task performed in the double Y
      maze or on retention and acquisition of 4-pair concurrent discrimination problems
      performed in a computer-automated touch screen testing apparatus. The results
      suggest that, although the perirhinal cortex and hippocampus can be functionally
      dissociated, their normal mode of operation includes the integration of object
      and spatial information.

PMID- 11508718
TI  - A possible role of the striatum in linear and nonlinear category learning:
      evidence from patients with Huntington's disease.
AB  - Linear and nonlinear categorization rule learning was examined in patients with
      Huntington's disease (HD) and a group of controls using the perceptual
      categorization task. Participants learned to categorize simple line stimuli into
      1 of 2 categories over 600 trials. In addition to traditional measures of
      accuracy, quantitative model-based analyses were applied to each participant's
      data to characterize better the nature of any observed deficits. In the linear
      rule condition, HD patients displayed an early-training deficit relative to
      controls, whereas later in training the HD patients were not statistically
      different from controls. In the nonlinear rule condition, HD patients displayed
      both an early- and late-training deficit. The quantitative model-based analyses
      revealed that the HD patients' deficits in the linear condition were due to an
      impairment in learning the experimenter-defined rule and not in applying a
      learned rule inconsistently. In the nonlinear condition, in contrast, the HD
      patients' deficits were due to an impairment in learning the experimenter-defined
      rule and in applying a learned rule inconsistently. Overall, these results
      suggest that HD can result in a deficit in learning both linear and nonlinear
      categorization rules.

PMID- 11508719
TI  - Lesions of the medial and lateral striatum in the rat produce differential
      deficits in attentional performance.
AB  - Excitotoxic lesions of the medial frontal cortex and anterior cingulate cortex in
      rats have been shown to produce dissociable impairments on a reaction time visual
      attention (5-choice) task. Because these cortical areas project to the medial
      striatal region, the authors predicted similar deficits after lesions of this
      striatal area compared with the lateral area. Compared with sham-operated
      controls, rats with quinolinic acid-induced medial striatal lesions showed all
      the behavioral changes associated with medial frontal cortex and anterior
      cingulate cortex lesions. In contrast, lateral striatal lesions produced profound
      disturbances in the performance of the task. Control tests showed little evidence
      of gross deficits in either group of rats in terms of motivation, locomotor
      function, or Pavlovian appetitive conditioning. These data suggest that the
      medial and lateral striatum have contrasting roles in the control of instrumental
      responding related to the primary sources of their cortical innervation.

PMID- 11508720
TI  - Functional disconnection of a prefrontal cortical-dorsal striatal system disrupts
      choice reaction time performance: implications for attentional function.
AB  - This series of experiments investigated the role of a prefrontal cortical-dorsal
      striatal circuit in attention, using a continuous performance task of sustained
      and spatially divided visual attention. A unilateral excitotoxic lesion of the
      medial prefrontal cortex and a contralateral lesion of the medial caudate-putamen
      were used to "disconnect" the circuit. Control groups of rats with unilateral
      lesions of either structure were tested in the same task. Behavioral controls
      included testing the effects of the disconnection lesion on Pavlovian
      discriminated approach behavior. The disconnection lesion produced a significant
      reduction in the accuracy of performance in the attentional task but did not
      impair Pavlovian approach behavior or affect locomotor or motivational variables,
      providing evidence for the involvement of this medial prefrontal corticostriatal
      system in aspects of visual attentional function.

PMID- 11508721
TI  - Selective loss of cholinergic neurons projecting to the olfactory system
      increases perceptual generalization between similar, but not dissimilar,
      odorants.
AB  - The neuromodulator acetylcholine is thought to modulate information processing in
      the olfactory system. The authors used 192 IgG-saporin, a lesioning agent
      selective for basal forebrain cholinergic neurons, to determine whether selective
      lesions of cholinergic neurons projecting to the olfactory bulb and cortex affect
      odor perception in rats. Lesioned and sham-operated rats were tested in an
      olfactory generalization paradigm with sets of chemically related odorants (n
      aliphatic aldehydes, acids, and alcohols). Lesioned rats generalized more between
      chemically similar odorants but did not differ from controls in their response to
      chemically unrelated odorants or in acquisition of the conditioned odor. Results
      show that cholinergic inputs to the olfactory system influence perceptual
      qualities of odorants and confirm predictions made by computational models of
      this system.

PMID- 11508722
TI  - Ultrasonic vocalizations as an index of social memory in female mice.
AB  - Ultrasonic vocalization (UV) as a measure of social memory was investigated in
      female mice. UVs emitted by a resident female in the presence of a same-sex
      partner were measured during a 3-min, pretest social interaction. In a second 3
      min test session, mice were reexposed to the familiar partner or presented with a
      novel partner. In the first case, there was a decline in UVs emitted by resident
      mice when the intervals between the 2 sessions were 15, 30, or 60 min. After 24
      hr, this effect disappeared. In contrast, with a novel female partner, the number
      of UVs remained unchanged. Scopolamine (0.05 mg/kg ip) disrupted this memory
      process: Drug-treated females did not show the expected decrease in UVs when
      reexposed to the familiar female after 30 min. This study provides behavioral and
      pharmacological evidence that ultrasonic calls can be used as a measure of social
      memory in female mice.

PMID- 11508723
TI  - Involvement of the entorhinal cortex in a process of attentional modulation:
      evidence from a novel variant of an IDS/EDS procedure.
AB  - Novel behavioral assays were used to assess the role of the entorhinal cortex in
      modulating attention to components of stimulus compounds. In Stage 1, rats
      received discrimination training with compounds constructed from 3 dimensions
      (auditory, visual, and tactile); in each compound the combination of components
      from 2 dimensions (e.g., auditory and visual) were relevant to the solution of
      the discrimination, and the remaining dimension (e.g., tactile) was irrelevant.
      In Stage 2, rats received a different discrimination in which the relevant
      dimensions were either congruent (auditory and visual) or incongruent (auditory
      and tactile) with those that were relevant in Stage 1. Sham-operated rats
      acquired the congruent discrimination more rapidly than the incongruent
      discrimination--a finding indicative of a process of attentional modulation-
      whereas rats with excitotoxic lesions of the entorhinal cortex acquired both
      discriminations equally readily.

PMID- 11508724
TI  - How do animals actually solve the T maze?
AB  - Rats were trained on a reinforced, delayed alternation T-maze task in the
      presence (cue group) or absence (no-cue group) of salient extramaze landmarks. A
      surprising finding was that the acquisition and memory performance of the 2
      groups did not differ. Manipulations of the extramaze landmarks for the cue group
      suggested that, although landmarks were used to guide behavior, other sources of
      information were also used normally. The no-cue group was able to perform the
      task at above-chance levels even when extramaze, intramaze, and inertial sources
      of orientation were manipulated. These results suggest that memory performance on
      the T maze does not rely exclusively on the processing of allocentric spatial
      relationships in the maze environment.

PMID- 11508725
TI  - Loss of the thalamic nuclei for "head direction" impairs performance on spatial
      memory tasks in rats.
AB  - This study sought to characterize the effects of removing the nuclei of primary
      importance in relaying the thalamic head direction signal to the hippocampal
      formation (the anterior dorsal [AD] and lateral dorsal [LD] nuclei) on the
      performance of a variety of spatial and nonspatial tasks. The results indicate
      that combined excitotoxic lesions of the AD and LD nuclei produce marked deficits
      on a variety of spatial tasks. These tasks included T-maze alternation and the
      ability to locate a hidden platform set at a fixed distance and fixed direction
      from a beacon in a Morris water maze. Although object recognition appeared
      unaffected, marked impairments were found in the ability to detect when an object
      was placed in a novel position (object-in-place memory).

PMID- 11508726
TI  - Ontogeny of spatial navigation in rats: a role for response requirements?
AB  - Three experiments investigated the role of response requirements in the Morris
      water maze for pre- and postweanling rats. Fischer-344N pups were required to
      locate a hidden platform using extramaze cues in a tank modified for the pups'
      immature response repertoire. Weanlings (20-22 days) displayed spatial learning
      in a pool 1/2 the size of the adults' (Experiment 1); by 26-28 days of age, probe
      performance was comparable to adults' on quadrant preference and platform
      crossing measures. Preweanlings (17 days), in a pool 1/3 the original size,
      significantly reduced escape latencies and displayed quadrant preference and
      platform-crossing scores indicative of spatial navigation. These results suggest
      that despite its protracted postnatal development, the preweanling hippocampus
      allows neural integration of visual-spatial information; however, the capacity to
      demonstrate such learning is dependent on task parameters and the pup's response
      repertoire.

PMID- 11508727
TI  - Behavioral effects of psychomotor stimulants in rats with dorsal or ventral
      subiculum lesions: locomotion, cocaine self-administration, and prepulse
      inhibition of startle.
AB  - Compelling evidence suggests a primary role for the mesoaccumbens dopaminergic
      pathway in the behavioral effects of amphetamine and cocaine, but the roles of
      other projections to the accumbens, including those arising in the hippocampal
      formation, are less clear. The authors evaluated the effects of discrete
      excitotoxic lesions of either the dorsal or ventral subiculum on the locomotor
      activating, reinforcing, and sensorimotor gating-disruptive effects of
      psychomotor stimulant drugs. Whereas dorsal subiculum-lesioned rats were
      hyperactive in tests of exploratory locomotion and startle reactivity, ventral
      subiculum-lesioned rats exhibited an attenuated locomotor response to
      amphetamine, moderately impaired acquisition of cocaine self-administration, and
      reduced levels of prepulse inhibition of startle. These 2 behavioral profiles
      overlap considerably with those previously observed in rats with lesions of the
      rostrodorsal and caudomedial accumbens, respectively, and suggest that
      projections from dorsal subiculum to accumbens core and ventral subiculum to
      accumbens shell exert distinct influences on behavioral responses that are
      amplified by psychomotor stimulant drugs.

PMID- 11508728
TI  - Association of intrinsic circadian period with morningness-eveningness, usual
      wake time, and circadian phase.
AB  - The biological basis of preferences for morning or evening activity patterns
      ("early birds" and "night owls") has been hypothesized but has remained elusive.
      The authors reported that, compared with evening types, the circadian pacemaker
      of morning types was entrained to an earlier hour with respect to both clock time
      and wake time. The present study explores a chronobiological mechanism by which
      the biological clock of morning types may be set to an earlier hour. Intrinsic
      period, a fundamental property of the circadian system, was measured in a month
      long inpatient study. A subset of participants also had their circadian phase
      assessed. Participants completed a morningness-eveningness questionnaire before
      study. Circadian period was correlated with morningness-eveningness, circadian
      phase, and wake time, demonstrating that a fundamental property of the circadian
      pacemaker is correlated with the behavioral trait of morningness-eveningness.

PMID- 11508729
TI  - The substrate for brain-stimulation reward in the lateral preoptic area: III.
      Connections to the lateral hypothalamic area.
AB  - Double-pulse tests were used to estimate the refractory periods and anatomical
      linkage of the reward-relevant fibers that course between the lateral preoptic
      and lateral hypothalamic areas. In the 1st study, pairs of conditioning and test
      pulses were delivered to each site, and the interval between pulses varied;
      recovery from refractoriness was similar at both sites, with the curves generally
      rising from 0.6 to 2.0 ms. In the 2nd study, the pairs of pulses were delivered
      to both sites. Six of 7 rats showed evidence of axonal collision, with estimates
      of conduction velocity that ranged from 0.48 to 8.95 m/s across rats. These
      results suggest that a wide spectrum of fiber types characterizes the reward
      relevant axons that course uninterruptedly between these 2 regions.

PMID- 11508730
TI  - Vasopressin in the lateral septum regulates pair bond formation in male prairie
      voles (Microtus ochrogaster).
AB  - Male prairie voles (Microtus ochrogaster) form a pair bond with a female partner
      after mating, and this behavior is regulated by the neuropeptide vasopressin
      (AVP). The authors report that AVP in the lateral septum is important for pair
      bond formation. Administration of an AVP V1a receptor antagonist in the lateral
      septum blocked mating-induced pair bonding, whereas administration of AVP induced
      this behavior in the absence of mating. In addition, administration of an
      oxytocin (OT) receptor antagonist in the lateral septum also blocked pair bond
      formation induced by either mating or AVP administration, suggesting that the OT
      receptor blockade may have interfered with the AVP regulation of behavior.
      Together, these data provide evidence suggesting that AVP in the lateral septum
      regulates pair bond formation in male prairie voles and that this process
      requires access to both AVP and OT receptors.

PMID- 11508731
TI  - Parabrachial nucleus lesions block taste and attenuate flavor preference and
      aversion conditioning in rats.
AB  - Rats with ibotenic acid lesions of the parabrachial nucleus (PBN) failed to learn
      a taste aversion induced by lithium chloride (LiCl) toxicosis. The same rats also
      did not learn to prefer a taste that was paired with intragastric (IG)
      carbohydrate infusions during 22 hr/day trials. The PBN-lesioned rats did learn
      to prefer a flavor (odor + taste) paired with the IG carbohydrate infusions over
      a different flavor paired with IG water. The PBN-lesioned rats also learned to
      avoid a flavor paired with IG LiCl infusions during 22 hr/day trials. The flavor
      preference and aversion, however, were less pronounced than those displayed by
      control rats. These data indicate that the PBN is essential for forming
      orosensory-viscerosensory associations when taste is the primary cue but is less
      critical when more complex flavor cues are available.

PMID- 11508732
TI  - Delay-dependent modulation of memory retrieval by infusion of a dopamine D1
      agonist into the rat medial prefrontal cortex.
AB  - Dopamine (DA) in the medial prefrontal cortex (PFC) can modulate the short-term
      retention of information and other executive functions. The present study
      examined whether administration of a DA D1 agonist into the PFC could have
      differential effects on memory retrieval in circumstances in which memory was
      either excellent or poor. Separate groups of rats were trained on a delayed
      version of the radial maze task. On the test day, the delay between the phases
      was either 30 min or 12 hr. Infusions of the D1 receptor agonist SKF 81297 (0.05,
      0.10, or 0.20 microg/0.5 microl) into the PFC before the test phase improved
      memory retrieval after a 12-hr delay but disrupted performance after a 30-min
      delay. These data suggest that D1 receptor activity can exert differential
      effects over PFC function, depending on the strength of the memory trace. When
      memory is decremented by an extended delay, activation of PFC DA D1 receptors by
      an agonist can improve cognitive function.

PMID- 11508733
TI  - Nucleus accumbens amphetamine microinjections unconditionally elicit 50-kHz
      ultrasonic vocalizations in rats.
AB  - The authors have hypothesized that, in adult rats, 50-kHz ultrasonic
      vocalizations (USVs) index a state characterized by high arousal and expectations
      of reward. This study was conducted to investigate whether dopamine agonism of
      the nucleus accumbens (NAcc) could evoke such an appetitive state, by examining
      the effects of NAcc amphetamine (AMPH) microinjections on USVs. Intra-NAcc AMPH
      injections (0.3, 1.0, 3.0, 10.0 microg unilaterally) produced robust, dose
      dependent increases in 50-kHz USVs, which could not be accounted for by
      concomitant increases in locomotor activity (LA). However, AMPH injections into
      dorsal control caudate putamen sites produced a modest, dose-dependent increase
      in LA without significant increases in 50-kHz USVs. These findings indicate that
      NAcc AMPH microinjections selectively evoke 50-kHz USVs in rats, supporting the
      notion that dopamine elevations in the NAcc may unconditionally elicit a state of
      reward anticipation.

PMID- 11508734
TI  - Rats with basolateral amygdala lesions show normal increases in conditioned
      stimulus processing but reduced conditioned potentiation of eating.
AB  - Rats with neurotoxic lesions of basolateral amygdala (ABL) and control rats
      showed comparable enhancement of attentional processing of a visual stimulus when
      its predictive value was altered. In contrast, lesioned rats showed less
      potentiation of eating than did control rats when food was available during
      presentations of a conditioned stimulus that was previously paired with food.
      When considered together with previous data, these results indicate a double
      dissociation between effects of lesions of the ABL and of the amygdala central
      nucleus on phenomena related to attentional processing and the acquisition of
      motivational value.

PMID- 11508735
TI  - Fear conditioning in inbred mouse strains: an analysis of the time course of
      memory.
AB  - Three mouse strains were examined for short- and long-term memory for Pavlovian
      fear conditioning measured 1 hr and 24 hr after conditioning. Both DBA/2J and
      CBA/J mice exhibit reduced long-term memory for contextual fear conditioning
      compared with C57BL/6J mice. In cued fear conditioning, however, DBA/2J mice show
      reduced short- and long-term memory compared with C57BL/6J mice, whereas CBA/J
      mice exhibit reductions only in short-term memory. These results underscore the
      importance of examining the time course of memory retention, and they suggest
      that inbred mouse strains may provide a diversity of phenotypes. The results also
      suggest that the processes of short- and long-term memory storage as well as
      contextual and cued fear conditioning are dissociable and are mediated by
      genetically distinct neurobiological mechanisms.

PMID- 11508736
TI  - Discrimination of computer-graphic stimuli by mice: a method for the behavioral
      characterization of transgenic and gene-knockout models.
AB  - An automated method is described for the behavioral testing of mice in an
      apparatus that allows computer-graphic stimulus material to be presented. Mice
      responded to these stimuli by making a nose-poke toward a computer monitor that
      was equipped with a touchscreen attachment for detecting responses. It was found
      that C57BL/6 mice were able to solve single-pair visual discriminations as well
      as 3-pair concurrent visual discriminations. The finding that mice are capable of
      complex visual discriminations introduces the possibility of testing mice on
      nonspatial tasks that are similar to those used with rats, monkeys, and humans.
      Furthermore, the method seems particularly well suited to the comprehensive
      behavioral assessment of transgenic and gene-knockout models.

PMID- 11508737
TI  - Chromatin and chromosomal fine structure in spermatogenesis of some species of
      amphibians.
AB  - Spermatogenesis is a complex differentiation process which is characterised,
      among other features, by conspicuous stage-specific nuclear events such as the
      pairing of homologous chromosomes coupled with the formation of synaptonemal
      complexes, the replacement of histones with sperm-specific proteins during
      spermiogenesis and, as a result, chromatin condensation and its inactivation in
      sperm cells. The chromatin of spermatogenic cells undergoes dramatic
      conformational changes upon differentiation from spermatogonia to mature
      spermatozoa. During the haploid stage of spermatogenesis, histones are gradually
      replaced, firstly by transition proteins and later by sperm-specific proteins. As
      a result of the high degree of condensation and inactivation of spermatid and
      sperm chromatin, Sertoli cells are responsible for the nourishment of germ cells
      with ribosomal RNA and nutritive substances.

PMID- 11508738
TI  - Cytogenetic analysis of caprine 2- to 4-cell embryos produced in vitro.
AB  - Prepubertal goat in vitro matured/in vitro fertilised oocytes produce only a
      small percentage of blastocysts. The present study examines the incidence of
      chromosomal anomalies in 2- to 4-cell embryos in vitro produced (IVP) from
      prepubertal oocytes fertilised with the semen of two males. Cumulus-oocyte
      complexes were obtained by slicing ovaries from slaughtered prepubertal goats.
      Oocytes were matured in TCM199 supplemented with 20% heat inactivated Donor
      Bovine Serum (DBS), 10 microg/ml FSH + 10 microg/ml LH + 1 microg/ml 17beta
      oestradiol for 27 h at 38.5 degrees C in 5% CO2 in air. IVM oocytes were
      inseminated with the sperm from two males prepared using the swim-up and heparin
      capacitation procedures. At 24 h postinsemination (hpi) the oocytes were
      transferred to 100 microl drops of SOF medium for a further 24 h. At 17 hpi a
      sample of oocytes was stained with lacmoid to evaluate the nuclear stage after
      fertilisation. The cleavage rate was determined at 24, 36 and 48 hpi and
      chromosome slides were prepared according to the gradual-fixation technique and
      stained with Leishman. A total of 1070 2- to 4-cell embryos from prepubertal goat
      oocytes were studied, but it was only possible to analyse 241 cytogenetically. Of
      these, 40% exhibited a normal diploid chromosome complement, 59% were haploid and
      1% were triploid. There were significant differences between the two males in
      sperm oocyte penetration and oocyte cleavage but no differences were found in
      chromosomal anomalies. In conclusion, the low number of embryos karyotyped and
      the high number of haploid embryos found in this study suggested a high incidence
      of abnormal fertilised embryos and deficient cytoplasmic maturation of the oocyte
      which inhibits sperm head decondensation.

PMID- 11508739
TI  - Zona pellucida solubility and cortical granule complements in human oocytes
      following assisted reproductive techniques.
AB  - In this study the solubility to alpha-chymotrypsin of the zona pellucida (ZP) of
      human oocytes and polyploid embryos obtained during various clinical procedures
      of assisted fertilisation (IVF, ICSI, cyropreservation) was evaluated. The aim of
      the study was to determine whether changes in ZP solubility occur during such
      procedures and whether abnormal solubility could be likened to fertilisation
      failure. Correlation between ZP solubility and cortical granule (CG) density was
      also studied. The results showed that ZP solubility varied considerably among
      germinal vesicle or metaphase oocytes obtained from different subjects, but was
      essentially identical for the oocyte cohort obtained from individual women. On
      the basis of ZP solubility metaphase oocytes were subdivided into two classes:
      class I, average ZP dissolution time +/- SE = 24.1+/-0.9 min, n = 28; and class
      II, 46.7+/-2.0 min, n = 13. Prolonged ZP dissolution times of metaphase oocytes
      were significantly correlated with a low in vitro fertilisation rate in sibling
      oocytes. The zonae of fertilised eggs (polyploid embryos) showed long
      solubilisation times (IVF: 45.3+/-3.4 min, n = 18; ICSI: 48.9+/-2.7 min, n = 19).
      ZP solubility of oocytes that failed to fertilise was intermediate between that
      of class I metaphase oocytes and embryos (unfertilised IVF: 33.0+/-2.7 min, n =
      13; unfertilised ICSI: 43.0+/-2.4 min, n = 9). A moderate spontaneous ZP
      hardening occurred when metaphase oocytes were cultured for 24 h. Finally,
      cryopreservation of unfertilised oocytes caused hardening of their ZP, with
      dissolution times that were comparable to those found in fertilised eggs (49.5+/
      2.3 min, n = 10). In most cases, an inverse correlation was found between ZP
      dissolution time and CG density (longer solubilisation times corresponding to
      lower CG density). ZP hardening caused by cryopreservation, however, was not
      associated with a significant reduction in CG density in most of the oocytes
      examined.

PMID- 11508740
TI  - In vitro development of reconstructed bovine embryos and fate of donor
      mitochondria following nuclear injection of cumulus cells.
AB  - In this study we examined the developmental potential of reconstructed embryos
      and the fate of donor mitochondria during preimplantation development after
      nuclear transfer in cattle. Isolated cumulus cells were used as donor cells in
      nuclear transfer. Cumulus cells labelled with MitoTracker Green FM fluorochrome
      were injected into enucleated bovine MII oocytes and cultured in vitro.
      MitoTracker labelling on donor cells did not have a detrimental effect on
      blastocyst formation following nuclear transfer. Cleavage rate was about 69%
      (56/81) and blastocyst formation rate was 6.2% (5/81) at 7 days after nuclear
      transfer. The labelled mitochondria dispersed to the cytoplasm and became
      distributed between blastomeres and could be identified up to the 8- to 15-cell
      stage. Small patches of mitochondria were detected in some 8- to 15-cell stage
      embryos (5/20). However, donor mitochondria were not detected in embryos at the
      16-cell stage and subsequent developmental stages. In the control group,
      mitochondria could be identified in arrested 1-cell embryos up to 7 days after
      nuclear transfer. These results suggest that disappearance of the labelled donor
      mitochondria in nuclear transfer bovine embryos is not due to fading of the
      fluorochrome marker, but is rather an as yet undefined cytoplasmic event.

PMID- 11508741
TI  - Maternal versus paternal expression of a LacZ transgene in preimplantation mouse
      embryos: effects of genetic background and 2-cell block.
AB  - The expression of a transgene NI-ROSA LacZ (LacZtg) trapped into the genes for
      two presumably untranslated, ubiquitously expressed RNAs, was studied in
      preimplantation mouse embryos with respect to penetrance (fraction of expressing
      embryos) and to localisation of beta-galactosidase activity. With maternal origin
      in NMRI mice beta-galactosidase was first detected within one dot in the
      cytoplasm of zygotes at 30 h post-hCG. The staining pattern progressed to small
      clusters and to dense, homogeneous staining of the entire cytoplasm during
      further development. Within the NMRI background, penetrance in utero was delayed
      by at least 6 h when the transgene was of paternal as compared with maternal
      origin. Paternal transgene expression increased marginally during culture to 50 h
      after explantation of embryos at 30-48 h post-hCG and remained low or decreased
      in the '2-cell block'. Expression of a paternal transgene in preimplantation
      embryos developing in utero was further delayed in the maternal MF1 as compared
      with the NMRI background. In contrast to NMRI x NMRI embryos with paternally
      derived transgene, expression increased with time during the 2-cell block in MF1
      x NMRI embryos. Thus, in the earliest phase of mammalian development expression
      of this LacZtg is influenced by parental origin, maternal genetic background and
      environment. The spatial distribution of the gene product is developmentally
      controlled.

PMID- 11508742
TI  - Protein translation during early cell divisions of sea urchin embryos regulated
      at the level of polypeptide chain elongation and highly sensitive to natural
      polyamines.
AB  - Protein synthesis was analysed following fertilisation in sea urchin.
      Fluctuations in the accumulation of neo-synthesised proteins were observed during
      the first cell cycles. Accurate translation analyses were performed from lysates
      prepared from early embryos. The lysates readily translated endogenous pre
      initiated mRNAs allowing the determination of elongation rates in the absence of
      re-initiation in vitro. The translation capacity of embryo lysates increased 18
      fold from 0 to 90 min after fertilisation, reflecting the increase in the amount
      of pre-initiated mRNAs during early development. Kinetics analysis at a short
      time interval during the course of early development (240 min) showed an overall
      increase in the elongation rate (> 10-fold) which is regulated by pauses in
      synchrony with the cell divisions. Elongation activity in the lysates was highly
      sensitive to the natural polyamines, spermine (ID50 = 0.2 mM) and spermidine
      (ID50 = 1.8 mM), indicating high potential regulation by the intracellular level
      of polyamines in embryos. The regulation in the elongation changes associated
      with the early embryo cell divisions is discussed in the light of the
      physiological fluctuations in polyamine concentrations.

PMID- 11508743
TI  - Expression of melatonin receptor transcripts (mel-1a, mel-1b and mel-1c) in
      Japanese quail oocytes and eggs.
AB  - Cloning and sequencing of the cDNA for avian melatonin (MEL) receptors have made
      it possible to investigate the expression of these receptors in different animal
      tissues and organs by reverse transcription polymerase chain reaction. Our study
      demonstrates for the first time, the presence of MEL receptor transcripts in
      maternal RNA from Japanese quail oocytes and in RNA from the early embryos of the
      laid eggs. Specific primers permitted discrimination between mel-1a, mel-1b and
      mel-1c receptor sequences, and special techniques used to obtain the biological
      material made it possible to avoid accidental contamination with cells of somatic
      origin. Mel-1c transcript was the main one found in the oocytes and was
      constantly present in the maternal RNA from individual ovulated oocytes, while
      mel-la and mel-1b transcripts were only sporadically present. All three MEL
      receptor transcripts appeared in the RNA from blastoderms of laid eggs, pointing
      to their de novo synthesis during uterine embryo development. The relative amount
      of the MEL receptor transcripts was low in relation to that of beta-actin,
      roughly 3 x 10(-4) the amount of control beta-actin transcript. The presence of
      MEL receptor transcripts and their de novo synthesis in the 24-h-old bird embryos
      point to their probable wider distribution and earlier appearance in development
      than originally thought; the existence of the corresponding functional receptor
      proteins in such early embryos has not previously been reported.

PMID- 11508744
TI  - Expression of pregnancy-associated glycoprotein 1 and 2 genes in in vivo, in
      vitro and parthenogenetically derived preimplantation pig embryos.
AB  - The objective of this study was to determine whether porcine PAG (poPAG) genes
      are expressed in embryos as they develop from the 1-cell stage to expanded
      blastocysts, and whether expression differed according to how embryos had been
      derived. Embryos at various preimplantation stages were assayed after in vivo
      fertilisation, after in vitro fertilisation of in vitro-matured oocytes, or
      following parthenogenetic activation of in vitro-matured oocytes. The presence of
      PAG transcripts was determined at the 1-, 2-, and 4-cell, compact morula and
      blastocyst stages by reverse transcription-PCR procedures with PAG 1- and PAG 2
      specific primers, followed by Southern blotting. The mRNAs for poPAG 1 and 2 were
      detected in in vitro-derived, in vivo-derived and parthenogenetically derived
      blastocyst stage embryos. In some replications poPAG 1 could be detected as early
      as the compact morula stage and poPAG 2 could be detected as early as the 4-cell
      stage. Our study revealed that poPAG 1 and 2 genes are expressed as early as the
      compact morula stage and 4-cell stage, respectively, in normal embryos and in
      parthenogenetically derived blastocysts. Thus it appears that the poPAGs are not
      maternally imprinted and they may be useful as potential candidates for markers
      of developmental competence.

PMID- 11508745
TI  - Cortical granule exocytosis in Bufo arenarum oocytes matured in vitro.
AB  - Denuded Bufo arenarum oocytes matured in vitro by progesterone treatment
      exhibited abnormal segmentation due to the penetration of more than one sperm.
      These oocytes were able to respond to activation stimuli and exhibited the
      external signs characteristic of activation. However, the prevention of
      polyspermy was not effective in these oocytes, which exhibited numerous sperm in
      their cytoplasm. The aim of this work was to analyse the cortical reaction in
      polyspermic Bufo arenarum oocytes matured in vitro. The result indicate that the
      cortical reaction of these oocytes seems to occur with a chronological sequence
      similar to that described for ovoposited oocytes of this species. In addition,
      when, 1 min after pricking, cortical granule exocytosis occurred, the oocytes
      became refractory to sperm entry, suggesting that they are able to establish a
      slow block to polyspermy.

PMID- 11508746
TI  - Phosphorylation of p90rsk during meiotic maturation and parthenogenetic
      activation of rat oocytes: correlation with MAP kinases.
AB  - This paper reports on the activation of p90rsk during meiotic maturation and the
      inactivation of p90rsk after electrical parthenogenetic activation of rat
      oocytes. In addition, the correlation between p90rsk and MAP kinases after
      different treatments was studied. We assessed p90rsk activity by examining its
      electrophoretic mobility shift on SDS-PAGE and evaluated ERK1+2 activity by both
      mobility shift and a specific antibody against phospho-MAP kinase. The
      phosphorylation of p90rsk during rat oocyte maturation was a sequential process
      that may be divided into two stages: the first stage was partial phosphorylation,
      which was irrelevant with MAP kinases because p90rsk phosphorylation took place
      prior to activation of MAP kinases. The second stage inferred full activation
      occurred at the time when MAP kinases began to be activated (3 h after germinal
      visicle breakdown). Evidence for the involvement of MAP kinases in the p90rsk
      phosphorylation was further obtained by the following approaches: (1) okadaic
      acid (OA) accelerated the phosphorylation of both MAP kinases and p90rsk; (2) OA
      induced phosphorylation of both MAP kinases and p90rsk in the presence of IBMX;
      (3) when activation of MAP kinases was inhibited by cycloheximide, p90rsk
      phosphorylation was also abolished; (4) dephosphorylation of p90rsk began to take
      place at 3 h post-activation, temporally correlated with the completion of MAP
      kinase inactivation; (5) phosphorylation of both kinases was maintained in
      oocytes that failed to form pronuclei after stimulation; (6) OA abolished the
      dephosphorylation of both kinases after parthenogenetic activation. Our data
      suggest that MAP kinases are not required for early partial activation of p90rsk
      but are required for full activation of p90rsk during rat oocyte maturation, and
      that p90rsk dephosphorylation occurs following MAP kinase inactivation after
      parthenogenetic activation of rat oocytes.

PMID- 11508747
TI  - Deficiency or opportunity?

PMID- 11508748
TI  - Comparison of unenhanced and contrast-enhanced spiral CT for assessing interval
      change in patients with colorectal liver metastases.
AB  - RATIONALE AND OBJECTIVES: The purpose of this study was to determine whether the
      interval change in hepatic colorectal metastases as assessed with serial computed
      tomographic (CT) scans without contrast material enhancement differs from that as
      assessed using serial, portal dominant phase, contrast-enhanced CT scans.
      MATERIALS AND METHODS: Unenhanced and contrast-enhanced abdominal CT scans were
      obtained in 28 patients. Three radiologists separately reviewed serial unenhanced
      and contrast-enhanced studies to assess the interval change in liver metastases.
      These radiologists recorded total number of lesions, bidimensional measurements
      of the largest lesions (as many as three), and overall impressions regarding the
      interval change (none, worse, or better). RESULTS: Among the 84 judgments (28
      patients x 3 radiologists), comparisons of unenhanced and contrast-enhanced CT
      studies were concordant in 60 assessments (71%). Nineteen (23%) showed mild
      disagreement. Of these, contrast-enhanced CT studies demonstrated disease
      stability when unenhanced CT studies demonstrated otherwise in 11 judgments,
      whereas unenhanced CT studies demonstrated stability when contrast-enhanced CT
      studies demonstrated otherwise in eight assessments. Furthermore, of the five
      marked disagreements, two resulted from a conclusion of interval improvement on
      unenhanced CT studies and a conclusion of interval worsening on contrast-enhanced
      CT studies, whereas three demonstrated the opposite. Neither set of serial CT
      studies systematically resulted in under- or overestimation of disease
      progression (McNemar Q test, P < .25). CONCLUSION: The authors found no
      consistent pattern to demonstrate that serial unenhanced or contrast-enhanced CT
      studies resulted in over- or underestimation of disease progression.

PMID- 11508749
TI  - Sonographic discrimination between benign and malignant breast lesions with use
      of disparity processing.
AB  - RATIONALE AND OBJECTIVES: The authors performed this study to evaluate whether a
      digital processing technique called disparity processing (DP) can improve the
      differentiation between benign and malignant breast masses at ultrasound (US)
      and, thus, reduce the number of benign lesions being sampled for biopsy.
      MATERIALS AND METHODS: During an US examination, a sonographer slightly varies
      the pressure of the probe on the breast surface. DP can be used to evaluate pairs
      of B scans that represent the different parts of this compression cycle. The
      apparent displacement of the tissue is measured with DP, and a new image, called
      a correlation map, is constructed. This new image illustrates the similarity
      between the speckle patterns around each point. The authors evaluated 25 solid
      lesions with DP. Results were compared with those from (a) histologic examination
      of specimens obtained with core or surgical biopsy or (b) cytologic examination
      of specimens obtained with fine-needle aspiration. RESULTS: All 25 lesions were
      correctly diagnosed with DP. There were no false-positive or false-negative
      findings. All malignancies demonstrated a relatively low-brightness halo around
      the lesion perimeter with evidence of discontinuity. All benign lesions were
      associated with relatively high-brightness, continuous halos. CONCLUSION: The
      results suggest that DP can help differentiate benign from malignant masses.

PMID- 11508751
TI  - Medial axis reformation: a new visualization method for CT angiography.
AB  - RATIONALE AND OBJECTIVES: The authors performed this study to evaluate a new
      method (medial axis reformation [MAR]) for visualizing three-dimensional vascular
      data at electron-beam computed tomographic (CT) angiography. MATERIALS AND
      METHODS: MAR was performed automatically with a personal computer-based
      workstation. After the region of interest was edited, voxels were divided into
      groups according to their path lengths. Centroids of groups were connected to
      form the medial axis. Then, the medial axis was refined with multiscale medial
      response. Bifurcations were also detected and refined. Finally, curved sections
      were generated through the branches and laid out onto a single image by using a
      splitting method. The authors performed MAR during electron-beam CT angiography
      of coronary arteries, common carotid arteries, and iliac arteries. RESULTS: MAR
      displayed curved sections of branched vessels on one image, cut through the axis
      of vessels to show the vessel diameter objectively, and allowed the viewing
      direction to be altered arbitrarily. CONCLUSION: Results of preliminary
      applications demonstrate that MAR is a valuable new visualization method for CT
      angiography.

PMID- 11508750
TI  - Bayesian regression methodology for estimating a receiver operating
      characteristic curve with two radiologic applications: prostate biopsy and spiral
      CT of ureteral stones.
AB  - RATIONALE AND OBJECTIVES: The authors evaluated two Bayesian regression models
      for receiver operating characteristic (ROC) curve analysis of continuous
      diagnostic outcome data with covariates. MATERIALS AND METHODS: Full and partial
      Bayesian regression models were applied to data from two studies (n = 180 and
      100, respectively): (a) The diagnostic value of prostate-specific antigen (PSA)
      levels (outcome variable) for predicting disease after radical prostatectomy
      (gold standard) was evaluated for three risk groups (covariates) based on Gleason
      scores. (b) Spiral computed tomography was performed on patients with proved
      obstructing ureteral stones. The predictive value of stone size (outcome) was
      evaluated along with two treatment options (gold standard), as well as stone
      location (in or not in the ureterovesical junction [UVJ]) and patient age
      (covariates). Summary ROC measures were reported, and various prior distributions
      of the regression coefficients were investigated. RESULTS: (a) In the PSA
      example, the ROC areas under the full model were 0.667, 0.769, and 0.703,
      respectively, for the low-, intermediate-, and high-risk groups. Under the
      partial model, the area beneath the ROC curve was 0.706. (b) The ROC areas for
      patients with ureteral stones in the UVJ decreased dramatically with age but
      otherwise were close to that under the partial model (ie, 0.774). The prior
      distribution had greater influence in the second example. CONCLUSION: The
      diagnostic tests were accurate in both examples. PSA levels were most accurate
      for staging prostate cancer among intermediate-risk patients. Stone size was
      predictive of treatment option for all patients other than those 40 years or
      older and with a stone in the UVJ.

PMID- 11508752
TI  - B-mode enhancement of the liver with microbubble contrast agent: a blinded study
      in rabbits with VX2 tumors.
AB  - RATIONALE AND OBJECTIVES: The purpose of this study was to evaluate the accuracy
      of contrast material-enhanced sonography in the detection of liver lesions by
      using an animal model. MATERIALS AND METHODS: A total of 36 rabbits, 12 normal
      and 24 with one, two, or more VX2 tumors implanted percutaneously, were imaged on
      an Acuson 128XP/10 with a 7-MHz sector transducer by a sonographer blinded to the
      study assignments. The sonographer assigned rabbits to four groups (no, one, two,
      more than two tumors) based on the number of lesions detected before and then
      after the intravenous bolus injection of 0.5 mL of AF0150. S-VHS video segments
      or pre- and postcontrast images were separated, randomized, and evaluated by a
      blinded reader. Necropsy served as the gold standard. RESULTS: Classification of
      rabbits as normal or tumor bearing on the precontrast images produced three false
      positive results and three false-negative results for the blinded sonographer and
      six false-positive results and two false-negative results for the blinded reader.
      On postcontrast images, all rabbits were correctly classified by both observers.
      The correlation of the classification of whether rabbits had no, one, two, or
      more tumors relative to the pathologic classification on precontrast images was
      poor to fair (K = 0.349 +/- 0.099 for the sonographer and 0.274 +/- 0.111 for the
      reader), whereas the postcontrast correlation was good to excellent (K = 0.924 +/
      0.099 for the sonographer and 0.809 +/- 0.076 for the reader). CONCLUSION:
      AF0150 markedly increased the ability of the sonographer and the blinded reader
      to distinguish normal from tumor-bearing animals and improved the classification
      of rabbits with more than one liver tumor.

PMID- 11508753
TI  - Diffusion-weighted echo-planar MR imaging of CNS involvement in systemic lupus
      erythematosus.
AB  - RATIONALE AND OBJECTIVES: The purpose of this study was to determine the range of
      findings at diffusion-weighted magnetic resonance (MR) imaging in patients with
      systemic lupus erythematosus (SLE) and central nervous system involvement.
      MATERIALS AND METHODS: Diffusion-weighted MR images were reviewed in 20 patients
      with SLE and correlated with clinical symptoms and findings at computed
      tomography, conventional MR imaging, MR angiography, or conventional angiography.
      RESULTS: Diffusion-weighted MR imaging showed acute or subacute lesions in nine
      of 20 patients (45%). In the other 11, it showed no abnormal findings or chronic
      lesions. In four of the nine patients with lesions, diffusion-weighted imaging
      primarily showed hyperintense lesions with decreased apparent diffusion
      coefficient (ADC), which indicates acute or subacute infarcts. In four other
      patients, it primarily showed iso- or slightly hyperintense lesions with
      increased ADC, suggesting vasogenic edema. In two of these four patients, the
      findings were consistent with hypertensive encephalopathy. In the other two,
      small hyperintense foci on diffusion-weighted images with decreased ADC were seen
      within the vasogenic edema. These foci presumably represent microinfarcts
      associated with SLE vasculopathy. In the ninth patient, diffusion-weighted
      imaging showed a small linear hyperintense lesion with normal ADC in the left
      parietooccipital region. CONCLUSION: Diffusion-weighted imaging shows primarily
      two patterns of acute or subacute parenchymal lesions in patients with SLE: acute
      or subacute infarction and vasogenic edema with or without microinfarcts.

PMID- 11508754
TI  - Effects of window and threshold levels on the accuracy of three-dimensional
      rendering techniques in coronary artery electron-beam CT angiography.
AB  - RATIONALE AND OBJECTIVES: The authors performed this study to evaluate the effect
      of window level and gray-scale threshold on the demonstration of coronary artery
      lumina at three-dimensional electron-beam computed tomographic (CT) angiography.
      MATERIALS AND METHODS: Forty-four coronary artery branches in postmortem pigs
      were evaluated with electron-beam CT angiography, and the findings were compared
      with those from conventional angiography. Images from electron-beam CT
      angiography were reconstructed with maximal intensity projection (MIP),
      multiplanar reformation (MPR), and shaded-surface display (SSD). Four categories
      of window level and gray-scale threshold were evaluated. RESULTS: Three
      dimensional electron-beam CT angiography accurately depicted the luminal
      diameters of the coronary arteries compared with conventional angiography (r =
      0.83-0.90, P < .0001). The length of lumina visualized at electron-beam CT
      angiography was significantly shorter than that visualized with conventional
      angiography (P < .001). The use of MPR enabled visualization of longer segments
      of coronary arteries than did the use of MIP or SSD (P < .05). The higher the
      window level and gray-scale threshold used, the smaller the coronary luminal
      diameters measured (P < .05). The most accurate window level and gray-scale
      threshold (82.6 HU +/- 29.8 and 89.5 HU +/- 29.7, respectively) were found to
      correspond to the attenuation of the lumina (275.8 HU +/- 58.8). Results of
      simple linear regression showed a strong correlation between luminal attenuation
      and window level (r = 0.89, P < .0001) or gray-scale threshold (r = 0.95, P <
      .0001). CONCLUSION: Electron-beam CT angiography shows promise in the
      visualization of coronary artery lumina. For accurate display of lumina, a proper
      window level and gray-scale threshold for three-dimensional rendering techniques
      should be determined and used on the basis of the attenuation of the target
      vessel.

PMID- 11508755
TI  - Take me to your (future) leader.

PMID- 11508756
TI  - Time management 101.

PMID- 11508757
TI  - Promotion based on teaching efforts requires ongoing documentation of scholarly
      teaching activities.

PMID- 11508758
TI  - Results of and comments on the 2000 survey of the American Association of
      Academic Chief Residents in Radiology.
AB  - RATIONALE AND OBJECTIVES: The American Association of Academic Chief Residents in
      Radiology (A3CR2) annually surveys radiology residency programs on issues related
      to training. The objective is to highlight national similarities, differences,
      and trends to help programs establish standards and improve residency training.
      MATERIALS AND METHODS: Questionnaires were mailed to 180 accredited diagnostic
      radiology residency training programs in the United States. The survey covered
      the usual general topics and more specific topics considered every 4 years; for
      2000 the latter were on-call issues and the chief residency year. RESULTS:
      Completed surveys were returned from 63 programs (35%). Important findings
      included increased caseload and call commitments, especially for smaller
      programs. Resident salaries appear to have increased more than the consumer price
      index. Nonemergent after-hour coverage and teleradiology are now a large part of
      the resident work practice. Women continue to be underrepresented, with a trend
      downward. Chief residents are more involved in organizing preparation for board
      examinations and have greater office facilities and more administrative duties.
      CONCLUSION: This survey provided useful insights. All levels of residency face
      increased workloads. On-call hours have not changed, but the work has intensified
      and the use of teleradiology has increased. Many programs have adopted a "night
      float" system, and nonemergent after-hours coverage should be considered in any
      program evaluation. Continued vigilance and sustained efforts are required to
      ensure that radiology is considered as a specialty by both men and women. With
      increased demands on attending physicians' time, chief residents may need to take
      on more administrative responsibilities.

PMID- 11508759
TI  - Assessing the potential versus the actual earnings of academic radiologists:
      effects of unequal duty service assignments.
AB  - RATIONALE AND OBJECTIVES: The purpose of this study was to determine if annual
      total work relative value units (RVUs) can be used to accurately compare
      physician productivity and effort among a small group of similarly trained
      radiologists. MATERIALS AND METHODS: The annual procedures for nine abdominal
      imaging radiologists were obtained. The work RVU was assigned to each procedure
      and summed for each radiologist. The daily work RVU mean earnings by duty service
      (eg, ultrasound [US], gastrointestinal radiology) were calculated for each
      radiologist and for the entire group. RESULTS: Annual total work RVUs earned by
      the six full-time radiologists ranged widely (5,000 to >9,000). Mean work RVUs
      earned per day by all the radiologists for each duty service also ranged widely
      (74 for US vs 23 for gastrointestinal radiology). The range of mean work RVUs
      earned per day by the radiologists within each duty service was narrower,
      however, and had almost no statistical significance. The wider range of annual
      total work RVUs earned by the radiologists resulted primarily from unequal
      distribution of duty service assignments. For example, radiologists with more
      days spent performing gastrointestinal radiology had lower annual total RVUs
      compared to radiologists with more days spent performing computed tomography or
      US. CONCLUSION: The RVU is an accurate measure of income production but may be an
      inaccurate measure of effort and individual productivity because of differences
      in duty assignments. In a relatively homogeneous group of
      radiologists/practitioners, such a comparison should be done within a duty
      service, or a correcting methodology should be used, because assignment to duty
      services rarely is equalized across physicians.

PMID- 11508760
TI  - Organizing the National Institute of Biomedical Imaging and Bioengineering. Part
      2.

PMID- 11508761
TI  - In vitro modified release of acyclovir from ethyl cellulose microspheres.
AB  - The aim of this study was to demonstrate a sustained-release microparticulate
      dosage form for acyclovir via an in vitro study. Ethyl cellulose was selected as
      a model encapsulation material. All of the microspheres were prepared by an oil
      in-water solvent evaporation technique. A 2(3) full factorial experiment was
      applied to study the effects of the viscosity of polymer, polymer/drug ratio, and
      polymer concentration on the drug encapsulation efficiency and the dissolution
      characteristics. The encapsulation efficiency of acyclovir in microspheres was in
      the range of 20.0-56.6%. Increase in the viscosity of ethyl cellulose and the
      ratio of CH2Cl2/ethyl cellulose increased drug encapsulation efficiency. The drug
      continuously released from microspheres for at least 12 h, and the release rate
      depended on the pH of the release medium. The sustained release characteristic
      was more prominent in the simulated intestine fluid than in the simulated gastric
      fluid. A faster release of drug was observed when a high viscosity polymer was
      used. The decomposition of acyclovir significantly decreased when encapsulated by
      ethyl cellulose, especially when stored at 37 and 50 degrees C.

PMID- 11508762
TI  - New strategy for the cultivation of microalgae using microencapsulation.
AB  - The four species of microalgae (Dunaliella bardawil, Chlorella minutissima,
      Pavlova lutheri and Haematococcus pluvialis) were immobilized in Ca-alginate
      capsules as a basic study for the development of the economic cultivation
      process. Under the batch culture of aerobic conditions, the thickness of the
      capsule membrane and CO2 supply did not affect the growth of the immobilized
      microalgae, Dunaliella bardawil. Cell concentration of immobilized microalgae in
      the capsule was higher than those of immobilized microalgae in beads and free
      cells. The cell concentrations of microencapsulated Dunaliella bardawil and
      Haematococcus pluvialis were five times greater than that of free cells. Based on
      these results, microencapsulation for the culture of microalgae was an effective
      method for the high-density cultivation. In comparison to the immobilized
      cultivation on the bioreactor type, it was more effective for the cultivation in
      the bubble column bioreactor than that in the stirrer tank bioreactor.

PMID- 11508763
TI  - Fabrication of porous poly(epsilon-caprolactone) microparticles for protein
      release.
AB  - The particle morphology and in vitro release of protein from porous and non
      porous PCL-F127 blended microparticles were evaluated. The BSA loaded PCL
      microparticles were prepared by the w/o/o/o emulsion-solvent evaporation method.
      Two types of homogenizer, a Polytron homogenizer and a probe ultrasonicator, were
      used to prepare the emulsion systems. The effects of solvent evaporation rate on
      the crystallinity and the performance of the microparticles were investigated.
      Both microparticles showed quite different shapes as well as surface morphology
      and release characteristics. The microparticles prepared with a Polytron
      homogenizer were quite porous in structure, which created channels for protein to
      continuously diffuse out, and resulted in sustained- and controlled-release
      characteristics. In addition, the initial burst release of protein from the
      microparticles was also reduced. Alteration of the evaporation rate of solvent
      did not change the crystallinity of the final microparticles. An influence of
      evaporation rate on the size of resulting microparticles was observed. The porous
      PCL microparticles were developed by choosing a proper homogenizer and
      fabrication conditions. Carefully controlling these variables resulted in
      microparticles with desirable release performance.

PMID- 11508764
TI  - Comparison of protein loaded poly(epsilon-caprolactone) microparticles prepared
      by the hot-melt technique.
AB  - This study was systematically designed to compare bovine serum albumin (BSA)
      loaded poly(epsilon-caprolactone) (PCL) microparticles based on a 2(3) factorial
      experiment. The microparticles were prepared by the holt-melt technique without
      using an organic solvent for polymer solubilization. The influence of the
      particle size of protein, protein/polymer ratio, and hydrophilic PEG on the
      surface morphology, particle size as well as the yield of PCL microparticles,
      encapsulation efficiency of BSA, and in vitro release properties were
      investigated. The structure of BSA remained its integrity using this technique.
      The mean particle size of BSA-loaded microparticles were in the range of 12.7 +/-
      0.1-16.9 +/- 0.8 microm, and all of the particles were smooth on the surface. The
      production yield of microparticles and the encapsulation efficiencies were high,
      and the values were in the range of 94.8 +/- 1.6%-98.1 +/- 1.0% and 94.9 +/- 9.6%
      98.6 + 0.3%, respectively. The burst release of BSA was in the range of 8.2 +/-
      0.4%-61.0 +/- 0.8%, which strongly depended on the formulation. None of three
      variables affected the yield of microparticles prepared from eight formulations
      (p > 0.05). However, the particle size of BSA significantly affected the size and
      the burst release as well as the cumulative release of protein in these
      microparticles (p < 0.05). The initial loading of BSA in terms of BSA/PCL ratio
      and the amount of PEG blended with PCL significantly affected all of the
      properties, except the yield (p < 0.05). The smaller the particle size of the
      BSA, the smaller the size of the resulting microparticles. Since the total
      surface area of the small particles was larger than that of the large particles,
      this accounted for the high burst release of protein from the microparticles
      encapsulating triturated-BSA.

PMID- 11508765
TI  - Mechanical properties of melamine-formaldehyde microcapsules.
AB  - The mechanical properties of melamine-formaldehyde (M-F) microcapsules were
      studied using a micromanipulation technique. Single microcapsules with diameters
      of 1-12 microm were compressed and held between two parallel planes, compressed
      and released, and compressed to burst at different speeds, whilst the force being
      imposed on the microcapsules and their deformation were measured simultaneously.
      This force increased as single microcapsules were compressed and then relaxed
      slightly as they were held. When the microcapsules were repeatedly compressed and
      released, a pseudo yield point was found for each microcapsule. Before the
      microcapsules were compressed to this point, the deformed microcapsules recovered
      to their original shape once the force was removed. However, when the deformation
      was beyond the 'yield point' there was profound hysteresis and the microcapsules
      showed plastic behaviour. As the microcapsules were compressed to burst at
      different speeds, ranging from 0.5-6.0 microm/s, it was found that their mean
      bursting forces did not change significantly. The deformations at the pseudo
      yield point and at bursting were also independent of the compression speed. On
      average, these melamine-formaldehyde microcapsules reached their 'yield point' at
      a deformation of about 19 +/- 1%, and burst at a deformation of 70 +/- 1%.

PMID- 11508766
TI  - The in-vitro and in-vivo characterization of PLGA:L-PLA microspheres containing
      dexamethasone sodium phosphate.
AB  - Dexamethasone sodium phosphate (DSP) is a widely used corticosteroid in the
      treatment of brain oedema associated with brain tumours. DSP has many side
      effects that limit its usage at an effective concentration. The objective of this
      study was to minimize these side effects by encapsulating DSP using biodegradable
      synthetic polymers, to extend the release time from microspheres and to evaluate
      the effectiveness in the treatment of brain oedema. Microspheres containing 5%
      DSP were formulated by the solvent evaporation method by using a 1:1 mixture of
      two synthetic polymers, poly(lactic-co-glycolic acid) and L-polylactic acid (PLGA
      and L-PLA). The surface morphologies and particle size distribution of the
      microspheres were investigated. The in-vitro release studies were performed in pH
      7.4 phosphate buffer solution. For determining the effectiveness of microspheres
      in the treatment of brain oedema, Sprague-Dawley rats weighing 200-250g were used
      as an animal model. Brain oedema was generated by the cold lesion method, and the
      effectiveness of the microspheres in treatment of oedema was investigated by the
      wet-dry weight method, lipid peroxidation ratios and histological evaluations.
      The average particle size of the microspheres was 13.04 +/- 2.05 microm, and the
      in-vitro release time of the microspheres was 8 h for 100/release. The degree of
      oedema was significantly different from the control group for the wet-dry weight
      method and lipid peroxidation ratio (p < 0.05). Similarly, histological
      evaluation of the tissues shoved that degree of oedema was significantly
      decreased with respect to the control group. All these results showed that
      implantation of microspheres was significantly more effective with respect to the
      systemic administration of DSP.

PMID- 11508767
TI  - Effects of the characteristics of chitosan on controlling drug release of
      chitosan coated PLLA microspheres.
AB  - Chitosan has been shown to be a biomaterial with good biocompatibility, and is
      highly biodegradable. This study investigated the effect of post-coating PLLA
      microspheres with different chitosans on the initial burst and controlling the
      drug release of the microspheres. Without chitosan, 19.2% of encapsulated
      lidocaine would release from PLLA microspheres within the first hour (R1), and
      the time of 50% release (T50) was 25 h. After the microspheres were coated with
      chitosan of viscosity (eta) 384 +/- 10cp, R1 and T50 could be reduced and
      prolonged to 14.6% and 90 h, respectively, for all tested molecular weights (Mw)
      of chitosan. In the case of the same Mw of chitosan being applied, the efficacy
      of reducing the initial burst of drug release was higher for a lower degree of
      deacetylation (D.D.). With chitosan in acetic acid solution, coating the
      microspheres with high Mw and high viscosity could most effectively reduce the
      initial burst and control drug release of PLLA microspheres. For example, the
      microspheres coated with chitosan solution of Mw 800 kDa and eta of 1479 cp, R1
      and T50 could be reduced and prolonged to 7.4% and 245 h, respectively. The study
      indicated that manipulating the viscosity of the chitosan solution was the most
      important factor in contributing to controlling the drug release of chitosan post
      coated PLLA microspheres.

PMID- 11508768
TI  - PLGA microsphere bioburden evaluation for radiosterilization dose selection.
AB  - The aim of this study was to determine the bioburden of PLGA microspheres
      produced by the solvent emulsion/extraction process as a means of determining an
      appropriate gamma-irradiation dose for sterilization. Bioburden was evaluated on
      the basis of ISO specifications. The analysis of initial microbial contamination
      was performed on blank microspheres, prepared by a non-aseptic laboratory scale
      process. A mean bioburden of 36.04 CFU (colony forming units)/110 mg microspheres
      was determined. Most of the detected germs originated from human commensal flora.
      According to the ISO dose-selection method, a gamma-irradiation dose of 19.6 kGy
      was found sufficient to ensure a sterility level of 10(-6). The effect of the
      selected irradiation dose on both the molecular weight of the polymer and the
      kinetics of 5-fluorouracil drug release from the microspheres was compared to the
      European Pharmacopeia recommended irradiation dose (25 kGy). This 20% reduced
      dose showed a lower extent of molecular weight reduction of PLGA and a better
      control of 5-FU release from microparticles. This can be related to reduce
      polymer radiation damage.

PMID- 11508769
TI  - Effects of inner water volume on the peculiar surface morphology of microspheres
      fabricated by double emulsion technique.
AB  - Poly(D,L-lactide-co-glycolide) (PLG, 65:35) was used to encapsulate bovine serum
      albumin (BSA) using a water-in-oil-in-water (W/O/W) double emulsion solvent
      extraction technique. To investigate the effects of an inner water/oil ratio on
      microsphere characteristics, microspheres were fabricated using four different
      formulations with a fixed oil volume of 12ml and the inner aqueous phase volume
      of 0.2ml, 0.3 ml, 0.4ml or 0.5 ml, respectively. Spherical microspheres were
      obtained after collection by filtration for formulations employing any of the
      four different inner water/oil ratios. However, microspheres with smaller inner
      water volumes tend to collapse after vacuum drying. The surface of the
      formulation with a higher inner water/oil ratio was shown to possess many more
      pores than that of the formulations with lower inner water/oil ratios. These
      pores may facilitate the water withdrawal during vacuum drying. Furthermore,
      microspheres with the lowest inner water/oil ratio (1/60) had higher initial
      burst release due to its larger surface area. However, microspheres with the
      highest inner water volume yield a faster release profile of BSA due to
      interconnected voids within microspheres and more pores on the surface.
      Therefore, the inner water/oil ratio is a crucial factor in the W/O/W double
      emulsion technique affecting the morphology and release kinetics of the resulting
      microspheres.

PMID- 11508770
TI  - Response surface methodology to obtain naproxen controlled release tablets from
      its microspheres with Eudragit L100-55.
AB  - PURPOSE: Naproxen CR tablets have been obtained from its microspheres prepared by
      coprecipitation with Eudragit L100-55. The purpose of this work was to evaluate
      the main and interaction effects of deaggregating agent concentration (X1),
      compression pressure (X2) and amount of precipitating water (X3) on naproxen
      release. A secondary purpose was to obtain an optimized naproxen controlled
      release solid oral dosage form with a predictable 12 h drug release. METHOD:
      Eudragit L100-55 (10 g) was dissolved in 100 ml of ethyl alcohol, and 30g of
      naproxen was dispersed in it with stirring. Purified water (100mL, cooled to 4
      degrees C) containing calcium chloride as a deaggregating agent was added to an
      alcoholic solution and homogenized. The mixture was filtered to obtain
      microspheres. Drug content analysis was performed spectrophotometrically at 332
      nm. Tablets were prepared by compressing microspheres containing 500mg of
      naproxen after adding 1% magnesium stearate. Dissolution was performed by the USP
      specifications of naproxen tablets. A 3-factor 3-level Box-Behnken design was
      employed to get 15 experimental runs. The independent variables used were X1, X2
      and X3. The dependent variables were dissolution at different time points with
      constraints on yield value and angle of repose of the microspheres, and hardness
      and thickness of the tablets. The dissolution constraints were placed such that
      the naproxen is released for 12 h by Higuchi's square root of time kinetics.
      RESULTS: The mathematical relationship obtained between X1, X2, X3 and the
      cumulative per cent of naproxen dissolved in 12 h with various constraints (Y5)
      was Y5 = 92.39 - 1.13X1 - 4.84X2 - 2.12X3 - 2.26X1X2 - 0.5X1X3 - 0.4X2X3 +
      2.4X(1)(2) - 0.4X(2)(2) (R2 = 0.9). The equation shows that X1, X2 and X3
      affected the release inversely, and the most significant interaction was between
      X1 and X2. Y5 has been maximized for optimization of naproxen release.
      CONCLUSIONS: Controlled release tablets of naproxen with predictable drug release
      characteristics were obtained by compressing its microspheres with Eudragit L100
      55.

PMID- 11508771
TI  - Microencapsulation of a synthetic peptide epitope for HTLV-1 in biodegradable
      poly(D,L-lactide-co-glycolide) microspheres using a novel encapsulation
      technique.
AB  - A novel procedure has been developed for the encapsulation of peptide antigens in
      poly(lactide-co-glycolide) (PLGA) microspheres, which employs trifluoro-acetic
      acid (TFA) as a carrier solvent for both the polymer and antigen. The
      antigen/polymer solution is emulsified in mineral oil containing sorbitan
      trioleate (Span 85) as an emulsifier and a low level of cottonseed oil to extract
      the TFA. Fluoresceinisothiocyanate-labelled bovine serum albumin (FITC-BSA) was
      used as a model antigen to characterize the microencapsulation. Microspheres were
      of the desired size (<10 microm) for targeting to antigen-presenting cells, and
      released the model antigen slowly after an initial burst release (11%) in
      PBS/0.02% Tween 80 at 37 degrees C. Subsequently, a potential peptide vaccine,
      designated MVFMF2, for the human T-lymphotropic virus type 1 (HTLV-1 ) was
      encapsulated at 4.7% loading using the novel oil-in-oil method. In vivo immune
      responses were examined in rabbits immunized with (i) encapsulated MVFMF2
      together with encapsulated adjuvant (N-acetyl-glucosamine-3yl-acetyl-L-alanyl-D
      isoglutamine, nor-MDP, (ii) encapsulated MVFMF2 without adjuvant, and (iii) free
      peptide with adjuvant. Inoculation of the encapsulated peptide produced an
      antibody response similar to that of the free peptide emulsified in adjuvant.
      Moreover, the elevated immune response elicited by the encapsulated peptide was
      observed without multiple booster immunizations and irrespective of whether an
      adjuvant was used. Additionally, the antibodies raised against both free and
      encapsulated MVFMF2 had similar affinities, as judged by competitive enzyme
      linked immunosorbant assay (ELISA), indicating that the encapsulated peptide
      retained a significant fraction of its epitopes. Hence, these results demonstrate
      that peptide vaccines can be encapsulated in PLGA microspheres using a common
      carrier solvent for both the peptide and polymer, which produces a desirable
      immune response in the absence of an adjuvant.

PMID- 11508773
TI  - Literature alerts.

PMID- 11508772
TI  - Impregnation and release of aspirin from chitosan/poly(acrylic acid) graft
      copolymer microspheres.
AB  - The purpose of this study was to produce aspirin-impregnated microspheres of
      chitosan/poly(acrylic acid) copolymer in order to evaluate the release
      characteristics as a function of pH, simulating the fluids in the
      gastrointestinal tract. Chitosan microspheres were obtained by the coacervation
      phase separation method, induced by the addition of a non-solvent (NaOH 2.0 M
      solution). The microspheres were cross-linked with glutaraldehyde, reduced with
      sodium cianoborohydride and grafted with poly(acrylic acid). The impregnation of
      aspirin into chitosan/poly(acrylic acid) copolymer microspheres was achieved by
      the dissolution of the drug in water:ethanol (2:1), which was adsorbed by the
      microspheres for 24h at 25 degrees C. The efficiency of aspirin impregnation was
      high (approximately 94%). The approach employed herein in the production of
      aspirin-impregnated microspheres using chitosan/poly(acrylic acid) can be a
      suitable drug-release control system.

PMID- 11508774
TI  - Noise-tolerant stimulus discrimination by synchronization with depressing
      synapses.
AB  - Some synapses between cortical pyramidal neurons exhibit a rapid depression of
      excitatory postsynaptic potentials for successive presynaptic spikes. Since
      depressing synapses do not transmit information on sustained presynaptic firing
      rates, it has been speculated that they are favorable for temporal coding. In
      this paper. we study the dynamical effects of depressing synapses on stimulus
      induced transient synchronization in a simple network of inhibitory interneurons
      and excitatory neurons, assuming that the recurrent excitation is mediated by
      depressing synapses. This synchronization occurs in a temporal pattern which
      depends on a given stimulus. Since the presence of noise is always a potential
      hazard in temporal coding, we investigate the extent to which noise in stimuli
      influences the synchronization phenomena. It is demonstrated that depressing
      synapses greatly contribute to suppressing the influences of noise on the
      stimulus-specific temporal patterns of synchronous firing. The timing-based
      Hebbian learning revealed by physiological experiments is shown to stabilize the
      temporal patterns in cooperation with synaptic depression. Thus, the times at
      which synchronous firing occurs provides a reliable information representation in
      the presence of synaptic depression.

PMID- 11508775
TI  - A neural mechanism of hyperaccurate detection of phase advance and delay in the
      jamming avoidance response of weakly electric fish.
AB  - The weakly electric fish Eigenmannia can detect the phase difference between a
      jamming signal and its own signal down to micros. To clarify the neuronal
      mechanism of this hyperaccurate detection of phase difference, we present a
      neural network model of the torus of the midbrain which plays an essential role
      in the detection of phase advances and delays. The small-cell model functions as
      a coincidence detector and can discriminate a time difference of more than 100
      micros. The torus model consists of laminae 6 and 8. The model of lamina 6 is
      made with multiple encoding units, each of which consists of a single linear
      array of small cells and a single giant cell. The encoding unit encodes the phase
      difference into its spatio-temporal firing pattern. The spatially random
      distribution of small cells in each encoding unit improves the encoding ability
      of phase modulation. The neurons in lamina 8 can discriminate the phase advance
      and delay of jamming electric organ discharges (EODs) compared with the phase of
      the fish's own EOD by integrating simultaneously the outputs from multiple
      encoding units in lamina 6. The discrimination accuracy of the feature-detection
      neurons is of the order of 1 micros. The neuronal mechanism generating this
      hyperacuity arises from the spatial feature of the system that the innervation
      sites of small cells in different encoding units are distributed randomly and
      differently on the dendrites of single feature-detection neurons. The mechanism
      is similar to that of noise-enhanced information transmission.

PMID- 11508776
TI  - Predicting the voluntary arm forces in FES-assisted standing up using neural
      networks.
AB  - For individuals with paraplegia, standing up requires activation of paralyzed leg
      muscles by an artificial functional electrical stimulation (FES) controller and
      voluntary control of arm forces by the individual. Any knowledge of such
      voluntary control, particularly its prediction, could be used to design more
      effective FES controllers. Therefore, artificial neural network models were
      developed to predict voluntary arm forces from measured angular positions of the
      ankle, knee, and hip joints during FES-assisted standing up in paraplegia. The
      training data were collected from eight paraplegic subjects in repeated standing
      up trials, and divided into two categories for training and validation. The
      predictions of the models closely followed both the training and validation data,
      showing good accuracy and generalization. The comparison of the models showed
      that, although there are striking similarities among the voluntary controls
      adopted by different subjects, each subject develops his/her own 'personal
      strategy' to control the arm forces, which is consistent from trial to trial. The
      level of consistency was dependent on the experience in using FES, injury level,
      body weight, and other subject-specific parameters.

PMID- 11508777
TI  - Evaluating causal relations in neural systems: granger causality, directed
      transfer function and statistical assessment of significance.
AB  - We consider the question of evaluating causal relations among neurobiological
      signals. In particular, we study the relation between the directed transfer
      function (DTF) and the well-accepted Granger causality, and show that DTF can be
      interpreted within the framework of Granger causality. In addition, we propose a
      method to assess the significance of causality measures. Finally, we demonstrate
      the applications of these measures to simulated data and actual neurobiological
      recordings.

PMID- 11508778
TI  - Mathematical models of eye movements in reading: a possible role for autonomous
      saccades.
AB  - An efficient method for the exact numerical simulation of semi-Markov processes
      is used to study minimal models of the control of eye movements in reading. When
      we read a text, typical sequences of fixations form a rather complicated
      trajectory - almost like a random walk. Mathematical models of eye movement
      control can account for this behavior using stochastic transition rules between
      few discrete internal states, which represent combinations of certain stages of
      lexical access and saccade programs. We show that experimentally observed
      fixation durations can be explained by residence-time-dependent transition
      probabilities. Stochastic processes with this property are known as semi-Markov
      processes. For our numerical simulations we use the minimal process method
      (Gillespie algorithm), which is an exact and efficient simulation algorithm for
      this class of stochastic processes. Within this mathematical framework, we study
      different forms of coupling between eye movements and shifts of covert attention
      in reading. Our model lends support to the existence of autonomous saccades,
      i.e., the hypothesis that initiations of saccades are not completely determined
      by lexical access processes.

PMID- 11508779
TI  - Coupling of posture and gait: mode locking and parametric excitation.
AB  - We investigate the temporal coordination of human gait and posture and infer the
      nature of their coupling. Participants viewed a sinusoidally oscillating visual
      display which induced medial-lateral postural sway during treadmill walking,
      while display frequency was varied (0.075-1.025 Hz). First, postural responses
      exhibited the usual low-pass characteristic but with an additional resonance peak
      near the preferred stride frequency, although shifted downward by 0.12 Hz; this
      provides evidence of a coupling from gait to posture. Second, the step cycle
      adapted to mode lock with the visual driver and postural sway, as well as
      displaying instances of intermittency (slipping in and out of phase) and
      quasiperiodicity (phase wandering); this provides evidence of a coupling from
      posture to gait. We observed a spectrum of integer mode locks, including a large
      1:1 trapping region about the stride frequency and superharmonic entrainment
      (stride frequency > driver frequency) at lower driver frequencies. A coupled
      oscillator model that incorporates a novel parametric coupling from posture to
      the gait "stiffness" term reproduces these features of the data, including the
      resonance peak shift. Biological coordination patterns may thus emerge naturally
      as properties of a system of appropriately coupled oscillators.

PMID- 11508780
TI  - Decreased IGF-I bioavailability after ethanol abuse in alcoholics: partial
      restitution after short-term abstinence.
AB  - IGF-I stimulates protein synthesis, lowers blood glucose, and affects cell
      differentiation. The main production site of IGF-I is the liver. One of its
      binding proteins, IGFBP-1, is also produced by the liver. It is well known that
      ethanol affects the function of the human liver. Long-term alcohol abuse may
      therefore not only cause considerable IGF-I and IGFBP-1 production changes, but
      also changes in IGF-I bioavailability, which at least in part is determined by
      the IGF-I/IGFBP-1 ratio. Not much is known about how the bioavailability of IGF-I
      is changed in alcohol abusers. Therefore, the objective of this investigation was
      to study that matter, and to elucidate how abstinence affects IGF-I
      bioavailability in man. Three study groups were formed: group N including normal
      non-addicted subjects, group E ethanol abusers without gross liver insufficiency,
      and group C alcohol abusers with liver cirrhosis and ascites. Serum
      concentrations of insulin, GH, IGF-1, and IGFBP-1 were determined in the morning
      in all participants, and the IGF-I/IGFBP-1 ratios were calculated. These values
      were compared in the three study groups. In group E comparison was also made
      between values recorded in the ethanol intoxicated and in the detoxicated states.
      Patients in group C had low IGF-I levels, high IGFBP-1 levels, and low IGF-I
      bioavailability as reflected by the IGF-I/IGFBP-1 ratios, which were several-fold
      reduced compared with subjects in group N (0.6+/-0.2 vs 10.2+/-2.3; p<0.001).
      Patients in group E had also a low IGF-I/IGFBP-1 ratio in the acute ethanol
      intoxicated state, which increased after detoxication (from 1.5+/-0.4 to 5.6+/
      1.2; p<0.01). It is concluded that alcohol abuse lowers the hepatic production of
      IGF-I and increases the production of IGFBP-1. This results in a reduced IGF-I
      bioavailability. However, in patients with not yet clinically apparent liver
      damage the IGF-I bioavailability increases if the alcohol abuse is stopped. These
      findings could reflect an important, physiological adaptation, since hypoglycemia
      may be induced if the blood glucose-lowering power of IGF-I remains strong at a
      time of ethanol-induced inhibition of the hepatic gluconeogenesis. Chronic
      alcohol abuse, causing liver cirrhosis, also leads to markedly reduced IGF-I
      bioavailability, which appears to become permanent, since it prevails more than
      one week after stopping the alcohol abuse.

PMID- 11508781
TI  - Naltrexone effect on pulsatile GnRH therapy for ovulation induction in polycystic
      ovary syndrome: a pilot prospective study.
AB  - The aim of the present study was to analyze the opioid influence on LH
      pulsatility in polycystic ovary syndrome (PCOS) patients and to evaluate the
      effectiveness of a long-term opioid antagonist (naltrexone) treatment in
      improving the pulsatile GnRH therapy which is successful in this syndrome. Ten
      obese women affected by PCOS participated in the study. Patients were
      hospitalized during the early follicular phase and underwent an oral glucose
      tolerance test (OGTT) with 75 g of glucose and a pulse pattern study followed by
      a GnRH test (100 pg i.v.). All patients were then treated for ovulation induction
      with pulsatile administration of GnRH (5 microg/bolus every 90 min). Since
      pregnancies did not occurr in any patient, after spontaneous or progestin-induced
      menstrual cycles, all patients received naltrexone at a dose of 50 mg/day orally
      for 8 weeks and during treatment repeated the basal protocol study and the
      ovulation induction cycle with the same modalities. The naltrexone treatment
      significantly reduced the insulin response to OGTT and the LH response to GnRH
      bolus, whereas it did not affect the FSH and LH pulsatility patterns. Concerning
      the ovulation induction by pulsatile GnRH, naltrexone treatment was able to
      improve, although not significantly, the ovulation rate (60% pre-treatment vs 90%
      post-treatment). Furthermore, the maximum diameter of the dominant follicle and
      the pre-ovulatory estradiol concentration were higher after long-term opioid
      blockade (follicular diameter 19.5+/-1.76 mm pre-treatment vs 21.6+/-2.19 mm post
      treatment, p<0.001; maximum estradiol level 728.7+/-288.5 pmol/l pre-treatment vs
      986.4+/-382.1 pmol/l post-treatment, p<0.05). During the naltrexone-pulsatile
      GnRH co-treatment two pregnancies occurred. In conclusion, our data show that
      naltrexone-pulsatile GnRH co-treatment is able to improve the ovarian
      responsiveness to ovulation induction in obese PCOS patients when compared to
      pulsatile GnRH alone. This action seems to be related to a decrease of insulin
      secretion. Further randomized studies should be performed in order to obtain
      significant conclusions on the possible clinical application.

PMID- 11508782
TI  - Functional hyperandrogenism detected by corticotropin and GnRH-analogue
      stimulation tests in women affected by apparently idiopathic hirsutism.
AB  - The etiologic diagnosis of hirsutism is often difficult. Previous studies have
      reported normal basal androgen and SHBG concentrations in 33-50% of hirsute
      women, suggesting the presence of an "idiopathic" form of hirsutism as the most
      frequent cause of this problem. The recent use of GnRH-analogues together with
      the corticotropin stimulation test allows better understanding of whether the
      cause of hirsutism is androgen excess and, if so, whether the origin of the
      latter is ovarian, adrenal or both. The present study evaluated adrenal and
      ovarian function in 48 young hirsute women as well as in 78 normal women matched
      for body mass index and age, who acted as control group. To determine ovarian
      function, a single 100-microg dose of GnRH analogue triptorelin was injected
      s.c.; thereafter, gonadotropins, 17-hydroxyprogesterone (17-OHP), delta4
      androstenedione (delta4), total testosterone (T) and estradiol were determined.
      To better understand the adrenal function, 250 microg of 1,24 ACTH were
      administrated as i.v. infusion for 5 h, and plasma cortisol (F), 17-OHP, A4,
      DHEAS, T, 11-desossicortisol were measured. The combined use of these two
      stimulation tests was able to detect mild to moderate abnormalities in the
      steroidogenesis of ovaries alone (23%), adrenals alone (16.6%), or both (35.4%)
      in most hirsute women (75%) with otherwise normal baseline androgen
      concentrations. In particular, patients showed significantly increased responses
      of 17-OHP, delta4, total T, 11-desossicortisol, and F to 1,24-ACTH
      administration. Moreover, they also had significantly higher 17-OHP and T
      responses to triptorelin. In conclusion, milder forms of functional ovarian
      and/or adrenal hyperandrogenism, similar to those found in clearly
      hyperandrogenic women, were observed and could be an underlying mechanism of
      idiopathic hirsutism.

PMID- 11508783
TI  - Absence of high-risk "s" allele associated with osteoporosis at the intronic SP1
      binding-site of collagen Ialpha1 gene in Southern Chinese.
AB  - The Sp1 polymorphism in the first intron of the collagen Ialpha1 gene was
      recently described to be associated with low bone mineral density (BMD) and
      increased fracture risk in Caucasian populations. The impact of this gene was
      assessed in a Southern Chinese population. One hundred and eighty-one women, aged
      51.1+/-8.8 yr were evaluated for the Sp1 polymorphism. Twenty-two per cent of the
      women were classified as having osteoporosis on the basis of a T-score at the
      lumbar spine or the hip below -2.5 with or without a prevalent fracture. Genotype
      analysis was performed by PCR amplification and restriction enzyme digestion.
      Single-strand conformational polymorphism analysis (SSCP) was performed in 65
      randomly selected samples to search for any polymorphic site in the PCR amplified
      region. The results showed that no restriction enzyme site could be identified in
      any of the 181 samples analyzed. Moreover, SSCP analysis revealed no polymorphism
      in the PCR amplified region of the first intron of the collagen Ialpha1 gene. In
      conclusion, the "s" allele, associated with low BMD and increased fracture risk
      in Caucasians, is non-existent or very rare in the Southern Chinese population.
      The absence of this "high risk" allele may in part account for the reduced
      fracture risk observed in the Chinese in comparison to Western populations.

PMID- 11508784
TI  - The effect of liver transplantation on circulating levels of estradiol and
      progesterone in male patients: parallelism with hepatopulmonary syndrome and
      systemic hyperdynamic circulation improvement.
AB  - The correction of hepatopulmonary syndrome (HPS) after liver transplantation (LT)
      remains controversial. The aims of our study were to: 1) analyze whether LT
      reverses HPS; 2) note any relationship between HPS and the systemic hemodynamic
      disturbance; and 3) note changes in circulating sex hormones and the possible
      association with pulmonary and systemic hemodynamic changes. Systemic hemodynamic
      parameters, cardiac output and systemic vascular resistance (SVR), sex hormones,
      and intrapulmonary vasodilatation assessed by contrast transesophageal
      echocardiography, and gas exchange abnormalities were investigated in 19 patients
      with advanced cirrhosis prior to and 6 months (176.8+/-30 days) after LT. LT was
      followed by a marked reduction in cardiac output (6.6+/-1.7 vs 3.5+/-0.5 l/min;
      p<0.001) and SVR (1039+/-460 vs 1978+/-294 dyn x sec x cm(-5); p<0.005). Before
      LT, circulating estradiol and progesterone levels were invariably elevated (66+/
      22 pg/ml and 1.8+/-1.1 ng/ml, respectively, normal values <31 pg/ml and 0.35
      ng/ml, respectively), and dropped after LT (28+/-12 pg/ml p<0.001 and 0.38+/-0.2
      ng/ml; p<0.001, respectively). Seventeen of 19 patients had intrapulmonary
      vasodilatation and increased alveolar-arterial oxygen difference, thereby
      fulfilling diagnostic criteria for HPS. Patients with HPS presented higher
      cardiac output (p<0.05), lower SVR (p<0.01), and higher progesterone and
      estradiol levels than patients without HPS (p<0.05). LT produced normalization of
      intrapulmonary vasodilatation in all patients. LT normalized hyperdynamic
      circulation and is a useful therapeutic option in patients with HPS.
      Normalization of sex hormone levels after LT suggests that they could play a
      pathogenic role in the development of HPS.

PMID- 11508785
TI  - Volume measurement with magnetic resonance imaging of hippocampus-amygdala
      formation in patients with anorexia nervosa.
AB  - The purpose of our work was to evaluate the volume of hippocampus-amygdala
      formation (HAF) in patients with anorexia nervosa (AN), being this structure a
      crucial target for the glucocorticoid action in the adaptative stress-response.
      AN patients have biochemical hypercortisolism associated to normal ACTH levels,
      but do not develop the characteristic clinical features of glucocorticoid
      hypersecretion. Furthermore, in these patients cortisol levels usually do not
      suppress after dexametasone challenge. Twenty AN females (aged 30.0+/-5.1) with
      10.5+/-4.2 yr of disease underwent a brain magnetic resonance (MR) examination
      during the recovery phase; an age-matched control group (CG) of 20 healthy female
      volunteers was also studied. Two interleaved T1-weighted spin-echo sequences for
      46 contiguous 2-mm coronal slices (pixel 0.98(2) mm) were used. The volumes of
      both right and left HAFs were calculated with manual contouring from the third
      ventricle to the Sylvian aqueduct. IGF-I, T3, gonadotropins, 24-h urine free
      cortisol, and BMI were obtained for both patients (on admission and on present
      evaluation) and CG. Mann-Whitney, Wilcoxon and Spearman tests were used. AN
      patients showed a significant (p=0.0001) reduction of total (right plus left) HAF
      volume (6.6+/-1.3 cm3) when compared with CG (8.9+/-1.1). No significant
      difference was found between right and left HAF in both patients and CG. In AN
      patients, no significant correlation was found between the HAF and all the
      hormonal parameters or BMIs, while a trend towards significance was observed with
      duration of the disease (r=-0.398; p=0.082). MR imaging demonstrated a
      significant volume reduction o

PMID- 11508786
TI  - Plasma and urinary GH following a standardized exercise protocol to assess GH
      production in short children.
AB  - Plasma and urinary GH responses following acute physical exercise were evaluated
      in 19 short-statured children (12 males, 7 females, median age: 11.4 yr, age
      range: 6.1-14.5 yr, Tanner stage I-III, height < or = 3rd centile for age; 7 with
      familial short stature, FSS; 8 with constitutional growth delay, CGD; 4 with GH
      deficiency, GHD) and 7 normally growing, age- and sex-matched control children (4
      males, 3 females, median age 11.0 yr, range: 7.2-13.1 yr, Tanner stage I-III).
      All patients and controls underwent a standardized exercise protocol (consisting
      of jogging up and down a corridor for 15 min, strongly encouraged to produce the
      maximum possible effort, corresponding to 70-80% of the maximal heart rate) after
      an overnight fasting. Samples for plasma GH determinations were drawn at 0 time
      (baseline), at 20 min (5 min after the end of exercise) and at 35 min (after 20
      min of rest); urine samples were collected before (0 time) and at 40, 80 and 120
      min after exercise. The distance covered by children with GHD during the test was
      significantly lower (p<0.05) than in the other groups of patients and controls.
      No differences in the pattern of plasma GH responses after physical exercise were
      found between children with FSS, CGD and healthy controls, the maximum percent
      increase (vs baseline) being evident at 20 min (median, FSS: +1125%; CGD: +1271%;
      controls: +571%). Children with GHD showed a smaller percent increase (+94%) of
      plasma GH, significantly lower (p<0.01) than those recorded in the other groups.
      A significant percent increase (p<0.01) of baseline urinary GH following exercise
      was found in children with FSS (median: +34%), CGD (+18%) and controls (+44%).
      Children with FSS and CGD showed a gradual increase of urinary GH, reaching the
      maximum at 80 min, while healthy controls had a more evident and precocious
      increase (maximum at 40 min). Urinary median GH levels did not change following
      physical exercise in children with GHD (-5%, not significant). A significant
      correlation was found between the maximal percent increase (vs baseline) of
      plasma and urinary GH following physical exercise (r=0.7, p<0.001). In
      conclusion, our results show that: 1) plasma and urinary GH responses (as well as
      the distance covered and the number of steps, i.e. the physical performance) to a
      standardized exercise protocol are similar in children with FSS, CGD and in
      normal-statured controls, being unable to differentiate among the "normal
      variants" of growth; 2) children with GHD, unable to accomplish the same
      performance of the other three groups, show significantly reduced plasma and
      urinary GH responses following physical exercise. Although the determination of
      GH responses to pharmacological stimuli remains the definitive tool for the
      diagnosis of GHD, these preliminary results seem to suggest a potential role of
      urinary (and plasma) GH response to a standardized exercise protocol as a safe,
      acceptable first screening test for GH sufficiency also in children, as
      previously reported in adults.

PMID- 11508787
TI  - In vivo and in vitro expression of somatostatin receptors in two human thymomas
      with similar clinical presentation and different histological features.
AB  - [(111)In-DTPA0]octreotide scintigraphy allows the in vivo visualization of
      several types of SS receptor (SSR)-expressing tumors. Among these, thymomas have
      been recently detected. Here we report on 2 patients admitted for myasthenia
      gravis and radiological evidence of thymic mass. Although these patients had
      similar clinical presentation, in vivo SSR scintigraphy displayed a difference in
      the degree of the [(111)In-DTPA0]octreotide uptake. Considering that both thymic
      masses had comparable volume, [(111)In-DTPA0]octreotide level was significantly
      higher in one of the 2 tumors (tumor/background ratio of 5.7 vs 2.6). The SSR
      subtype expression pattern was studied in vitro on the surgically resected
      specimens by ligand binding techniques, quantitative reverse transcriptase
      polymerase chain reaction (RT-PCR) and immunohistochemistry. According to the
      recent World Health Organization classification, the 2 tumors were classified A
      and B2 thymomas respectively. In membrane homogenates, we found a higher number
      of high affinity [125I-Tyr11]-SS-14 binding sites in the B2 thymomas (23.5+/-2.5
      vs 12.0+/-0.4 fmol/mg membrane protein; p<0.05). RT-PCR analysis showed sst1,
      sst2A and sst3 mRNA in the 2 thymoma tissues, whereas SS mRNA was detectable only
      in the A thymoma. Quantitative evaluation of RT-PCR data showed a comparable
      expression of the relative amount of sst2A mRNA in both tumors, whereas a
      significant higher expression of sst3 mRNA in the B2 thymoma. Sst2A
      immunoreactivity was localized mainly on the endothelium of intratumoral vessels,
      whereas sst3 was present on either tumoral epithelial cells or normal reactive
      thymocytes. The expression of sst2A receptors in these tumors is in line with the
      in vivo visualization by [(111)In-DTPA0]octreotide, which is considered a sst2
      preferring ligand. However, since radioligand uptake was significantly higher in
      the B2 thymoma, which expressed the largest sst3 mRNA levels, it might be
      possible that this subtype is involved in determining the tumor visualization
      during SSR scintigraphy. Apart from the affinity of the radioligand for the
      receptor, also the efficacy of the internalization of the radioligand-receptor
      complex might play a role in radioactivity accumulation during in vivo SSR
      scintigraphy. In fact, although octreotide binds with lower affinity to sst3
      receptors, this subtype displayed the highest amount of agonist-dependent
      receptor internalization compared to the other SSR subtypes. Moreover, sst3 was
      localized on both tumor cells and reactive thymocytes, and these latter cells are
      characterized by a very active turnover of membrane molecules. Finally, although
      more cases need to be evaluated, the lack of detection of SS mRNA in the tumor
      presenting a more aggressive phenotype (B2 thymoma) might have physiopathological
      or prognostic significance.

PMID- 11508788
TI  - Bilateral testicular adrenal rest tissue in congenital adrenal hyperplasia: US
      and MR features.
AB  - We describe magnetic resonance (MR) and ultrasonography (US) features of
      bilateral testicular adrenal rest tissue in a 20-yr-old man with congenital
      adrenal hyperplasia (CAH). Scrotal ultrasonology detected bilateral homogeneous
      hypoechoic lesions with well-defined margins and without evidence of sound
      attenuation. MR is useful in defining the size of lesions, because the contrast
      resolution is better than with sonography and allows an accurate definition of
      the extent of disease. This case suggests that US evaluation should be included
      in periodical follow-up of patients with CAH, while MR may be used in the case of
      rapid increase in the size of the testicular mass.

PMID- 11508789
TI  - Sustained remission of metastatic adrenal carcinoma during long-term
      administration of low-dose mitotane.
AB  - We present our experience with two female patients suffering from metastatic,
      recurrent adrenocortical carcinomas, to whom o,p'-DDD (mitotane) was administered
      for unusually long duration. The first patient received mitotane as monotherapy
      after relapse (in doses ranging from 3 to 6 g/day initially and 1 g/day
      thereafter, for 13 yr). The second patient presented with metastatic disease and
      underwent radical surgical excision of the adrenal. Mitotane was administered
      initially at 2.5 g/day, and the dose was gradually lowered over 8 yr to 1 g/day,
      without interruption. Both patients tolerated the medication well, regardless of
      the daily dosage, with complaints limited to epigastric pain and nausea, while
      their disease has been kept under control for 14 and 16 yr, respectively. The
      blockade of steroid synthesis with mitotane resulted in hypercholesterolemia in
      both patients and in premature menopause in the second patient; however, these
      abnormalities were taken care of with the appropriate therapy. The excellent
      follow-up of these patients suggests that even in hopeless cases with metastatic
      adrenocortical carcinoma, mitotane should be administered for very long periods
      of time as it can be well-tolerated and may be beneficial in the long run.

PMID- 11508790
TI  - P53 mutations in thyroid carcinoma: tidings from an old foe.
AB  - The underlying mechanism leading to carcinogenesis involves genomic instability,
      likely related to aneuploidy. While p53 as a "guardian of the genome" is an
      appealing candidate as an initiator of genomic instability, its mutations or
      deletions usually occur late in the course of tumor progression. P53 may,
      however, become a target of events initiated by genomic instability. P53 is a
      transcription factor with multifaceted regulatory functions in the cell cycle,
      DNA repair and apoptosis. Inactivating p53 mutations have been described in some
      50% of human cancers. These mutations are not only important in tumor progression
      but apparently also in the response of some tumors to chemotherapy and radiation
      treatment, thus to clinical outcome. P53 mutations are found in 14% of malignant
      thyroid tumors and are more frequent in poorly differentiated and anaplastic
      tumors. We have examined the mutation rates of p53 as a measure of genomic
      instability (hypermutability) of malignant thyroid tumors. We also wondered
      whether radiation enhances this tendency to genomic instability. To those ends we
      extracted all available entries from the p53 mutations database
      (http://www.perso@curies.fr), verified, extended where applicable, and
      supplemented that information from the original published reports. We were able
      to locate 100 entries. The distribution of the types of p53 aberrations in
      thyroid cancer was similar to those in the database as a whole. The silent
      mutation rate of 20%, not different from the expected 25%, is consistent with a
      random occurrence of these mutations. This silent mutation rate is 130 times that
      expected and is 7 times that of the p53 database. Moreover the distribution of
      p53 mutations is compatible with Poisson's distribution, which, when considered
      in the context of the silent mutation rates, indicates that p53 is particularly
      hypermutable in thyroid cancer. Epigenetic deamination of CpG dinucleotides at
      highly transforming DNA-contact residues is a feature of poorly differentiated
      tumors and thus associated with tumor progression. The rates of p53 mutations in
      radiation-related thyroid cancers (15.4%) are similar to those in spontaneously
      arising tumors, although there was a highly significant heterogeneity (p<0.0005)
      in the residues mutated in the two tumor sets. None of the residues mutated in
      radiation-related thyroid cancer involved CpG deamination. Based on the evidence
      of p53 hypermutability, thyroid cancer appears to exhibit remarkable genomic
      instability. Spontaneous epigenetic mutational events are involved in tumor
      progression. While thyroid cancer related to radiation exposure does not increase
      the rates of p53 mutation, they exhibit mutation at residues not involved in
      p53/DNA interface.

PMID- 11508791
TI  - A subject with abnormally short stature from Imperial Rome.
AB  - In spite of the rich iconographic and literary documentation from ancient
      sources, the skeletal evidence concerning individuals of abnormally short stature
      in the Greco-Roman world is scarce. The necropolis of Viale della Serenissima/Via
      Basiliano in Rome, mostly referable to the II century AD, recently yielded the
      skeleton of an individual characterized by proportionate short stature, gracile
      features suggesting female gender, and delayed epiphysial closure, associated
      with full maturation of the permanent dentition. These characteristics could be
      compatible with the phenotype associated with female gonadal dysgenesis. The
      skeletal individual described here, although poorly preserved, represents the
      first evidence of a paleopathologic condition affecting skeletal growth
      documented for the population of ancient Rome.

PMID- 11508792
TI  - Effect of acute hyperglycemia on potassium (86Rb+) permeability and plasma lipid
      peroxidation in subjects with normal glucose tolerance.
AB  - Hyperglycemia is likely to be one of the important determinants of ion transport
      as it is known to induce oxidative stress and may thus enhance non-specific
      permeability of membranes. The aim of the present study was to evaluate the
      effects of an acute increase in glycemia on 86Rb+ (a marker for K+) influx and
      lipid peroxidation. We evaluated the 75-g oral glucose tolerance test (OGTT)
      induced modification on 86Rb+ influx and plasma lipid peroxidation in 20 subjects
      with normal glucose tolerance (NGT). After 2-hour glucose loading, the levels of
      passive 86Rb+ influx and plasma lipid peroxidation were significantly increased,
      whereas the active influx of 86Rb+ was unchanged. The total and passive influx of
      86Rb+ into erythrocytes was significantly correlated with the level of plasma
      lipid peroxidation. This study demonstrates that acute hyperglycemia induces an
      increase in the passive influx of 86Rb+ in subjects with NGT, suggesting that
      acute hyperglycemia may produce an oxidative stress in plasma. These changes may
      be among the earliest changes occurring in response to hyperglycemia.

PMID- 11508793
TI  - Pro-atrial natriuretic peptide hormone from right atria is correlated with
      cardiac depression in septic patients.
AB  - N-terminal pro-atrial natriuretic peptide [proANP(1-98)] has been extensively
      investigated in patients with chronic heart failure and ishemic heart disease. It
      is found to be a better marker of cardiac dysfunction than atrial natriuretic
      peptide (ANP). The possible involvement of proANP(1-98) in cardiac depression
      caused by sepsis has not been studied yet. Therefore, we analyzed atrial plasma
      concentration of proANP(1-98) in 17 septic patients with hemodynamic variables
      measured or calculated using pulmonary artery catheter. The results of altogether
      96 measurements show a significant negative correlation of proANP(1-98) and
      cardiac index (p<0.024), oxygen delivery (p<0.03) and oxygen consumption
      (p<0.03). There is also a positive correlation with pulmonary vascular resistance
      (p<0.03). ProANP(1-98) is significantly higher in patients who developed acute
      respiratory distress syndrome (ARDS) (p<0.001). This study implies that proANP(1
      98) is a possible novel hormone marker of cardiac depression caused by sepsis
      that could be used for prediction of ARDS.

PMID- 11508794
TI  - DNA commission of the International Society of Forensic Genetics: recommendations
      on forensic analysis using Y-chromosome STRs.
AB  - During the past few years the DNA commission of the International Society of
      Forensic Genetics has published a series of documents providing guidelines and
      recommendations concerning the application of DNA polymorphisms to the problems
      of human identification. This latest report addresses a relatively new area,
      namely Y-chromosome polymorphisms, with particular emphasis on short tandem
      repeats (STRs). This report addresses nomenclature, use of allelic ladders,
      population genetics and reporting methods.

PMID- 11508795
TI  - Intranuclear ubiquitin immunoreactivity in the pigmented neurons of the
      substantia nigra in fire fatalities.
AB  - To evaluate the significance of immunohistochemical staining of ubiquitin (heat
      shock protein) in the midbrain for medico-legal investigation of death in fires,
      we examined forensic autopsy cases of fire fatalities (n = 35) in comparison with
      controls (n = 27; brain stem injury, acute myocardial infarction and carbon
      monoxide poisoning other than fire fatality). There were two intranuclear
      staining patterns in the nuclei of pigmented substantia nigra neurons: a type of
      inclusion (possible Marinesco bodies) and a diffuse staining. Percentage of
      nuclear ubiquitin positivity (Ub-positive %) in fire fatalities (2.7-44.7%; mean,
      18.5%) was significantly higher than in brain stem injury (n = 9; 0-10.4%; mean,
      4.5%) and myocardial infarction (n = 14; 1.5-14.6%; mean, 6.9%), independently of
      blood carboxyhemoglobin (COHb) levels. Age-dependent increase in Ub-positive %
      was observed in lower COHb (< 60%) cases. The intranuclear diffuse ubiquitin
      staining was not observed in cases of high blood cyanide level (> 1.0 microg/ml).
      These observations showed that intranuclear ubiquitin immunoreactivity of the
      pigmented substantia nigra neurons in the midbrain was induced by severe stress
      in fires.

PMID- 11508796
TI  - No stress--no whiplash? Prevalence of "whiplash" symptoms following exposure to a
      placebo rear-end collision.
AB  - Volunteer studies of experimental, low-velocity rear-end collisions have shown a
      percentage of subjects to report short-lived symptoms, but the cause of these
      symptoms remains unknown. It is unclear whether the symptoms arise from
      biomechanical stress causing injury or from psychological stress causing symptom
      expectation and anxiety. Similarly, the cause of symptoms remains obscure in
      virtually all "whiplash" patients because it is impossible to identify acute
      pathology in many cases. In this study subjects were exposed to placebo
      collisions that almost completely lacked biomechanical stress. It was highly
      probable that if the symptoms reported following low-velocity collisions were not
      due to injury but to other factors (including misattribution of symptoms from
      other sources), then the proportion of subjects reporting symptoms would be
      similiar to that reported for volunteers in true (experimental) low-velocity,
      rear-end collisions. A total of 51 volunteers (33 males and 18 females, mean age
      32.4 years) were recruited through local newspaper advertisements. An
      experimental set-up for a placebo collision was constructed using two standard
      European cars. At time T0, prior to the placebo collision, a history and physical
      examination was performed, including a psychological analysis (Freiburger
      Personality Inventory). A symptom history and physical examination were also
      performed at time T1, immediately after the placebo collision, and the subjects
      completed symptom questionnaires 3 days (time T2) and 4 weeks (time T3) after the
      placebo collision. Data analysis included a determination of the predictive value
      of psychological data for the presence of symptoms following exposure to a
      placebo collision. At time T1, 9 out 51 participants (17.6%) indicated symptoms.
      Within 3 days (time T2) after the placebo collision, 10 (19.6%) of the subjects
      had symptoms, and within 4 weeks (time T3) 5 subjects (9.8%) had symptoms. Of the
      last group, two of the five did not relate these symptoms to the "collision".
      Subjects who endorsed symptoms at time T1 had significantly higher scores on the
      psychological scale of psychosomatic disorders (measured at time T0). Subjects
      endorsing symptoms at time T2 had significantly higher scores on emotional
      instability. There was also a tendency to higher scores on this sub-scale for
      subjects with whiplash-associated disorders (WAD) at time T3. A discriminant
      analysis using all four psychological scales from time T0 had a power of 87%, 83%
      and 92% for correct classification of subjects as asymptomatic times T1, T2 and
      T3, respectively. Approximately 20% of subjects exposed to placebo, low-velocity
      rear-end collisions will thus indicate WAD, even though no biochemical potential
      for injury exists. Certain psychological profiles place an individual at higher
      risk for phenomenon.

PMID- 11508797
TI  - Markers of cardiac oxidative stress and altered morphology after intraperitoneal
      cocaine injection in a rat model.
AB  - This study was designed to assess the parameters of myocardial oxidative stress
      and related cardiac morphological changes following intraperitoneal cocaine
      exposure in rats. The cardiac levels of reduced glutathione(GSH), oxidised
      glutathione(GSSG), ascorbic acid (AA), and the production of malondialdehyde
      (MDA) were measured, as well as the variations of activity in the enzyme systems
      involved in cell antioxidant defence, glutathione peroxidase (GSH-Px),
      glutathione reductase (GR) and superoxide dismutase (SOD). After chronic cocaine
      administration for 30 days GSH was significantly depleted in the heart from 30
      min (P < 0.001) to 24 h (P < 0.001) after exposure, and GSSG was increased for a
      similar time (P < 0.05 at 30 min and P < 0.01 at 24 h). SOD increased during the
      first hour (P < 0.001), GR and GSH-Px both increased from 30 min to 24 h, and
      these increases were statistically significant (P < 0.01 and P < 0.001 at 30 min
      and P < 0.01 and P < 0.001 at 24 h, respectively). The AA levels increased after
      1 h (P < 0.01), remaining significantly so for 24 h (P < 0.001) and MDA increased
      from 30 min to 24 h, all values being highly significant (P < 0.001). The body
      weight was significantly (P < 0.001) reduced in both cocaine groups (40 mg/kg x
      30 days and 40 mg/kg x 10 days + 60 mg/kg x 20 days). The heart weight (P < 0.01)
      and its percentage of the body weight (P < 0.001) were significantly higher in
      these two groups than in the controls. Similarly, in the noradrenaline 4 mg/ kg x
      30 days group, the body weight was significantly (P < 0.001) reduced and the
      heart weight (P < 0.01) and its percentage of body weight (P < 0.001) were
      significantly higher than in the controls. In comparing the cocaine and
      noradrenaline experiments, the frequency and extent of cardiac lesions obtained
      with 40 mg/kg x 10 days + 60 mg/kg x 20 days of cocaine were similar to those
      with 8 mg/kg of noradrenaline at 24 h. In this experimental model, cocaine
      administration compromised the antioxidant defence system of the heart associated
      with a significant increase of heart weight and the percentage of body weight.

PMID- 11508798
TI  - Sudden unexpected death in young adults with chronic hydrocephalus.
AB  - We present four cases of sudden unexpected death in young adults with chronic
      hydrocephalus. The patients were between 20 and 28 years of age and had suffered
      from aqueduct stenosis (two patients), spina bifida in combination with Arnold
      Chiari malformation (type II) and fragile X-syndrome. The patients suddenly
      collapsed with cardiorespiratory failure and could not be resuscitated and none
      had a history of headache or seizures. The post-mortem examinations revealed no
      unusual findings and a definite cause of death could not be established.
      Neuropathological examination revealed chronically hydrocephalic brains without
      any signs of uncal or tonsillar herniation. We hypothesise that a sudden pressure
      induced decompensation of cerebral neuronal pathways involving insular and limbic
      cortex, hypothalamus and brain stem nuclei, may have caused disturbances of the
      cardiopulmonary control centres in the reticular formation of the brain stem,
      which in turn may have led to instantaneous cardiorespiratory arrest resulting in
      sudden "neurogenic" cardiac death.

PMID- 11508799
TI  - Course of glial immunoreactivity for vimentin, tenascin and alpha1
      antichymotrypsin after traumatic injury to human brain.
AB  - In a total of 104 individuals who had sustained traumatic brain injury (TBI), the
      course of glial immunoreactivity was investigated at the injured cortical area
      during the first 30 weeks after the trauma, in order to provide data for a
      forensic wound age estimation. Glial cells were stained with antibodies against
      the intermediate filament protein vimentin, the extracellular matrix protein
      tenascin and the serine protease inhibitor alpha1-antichymotrypsin (alpha1-ACT).
      Injury-induced glial staining reactions could be observed, at the earliest, after
      a post-infliction interval of 3.1 h for alpha1-ACT, 22 h for vimentin and 7 days
      for tenascin.

PMID- 11508800
TI  - Trajectory reconstruction from trace evidence on spent bullets. II. Are tissue
      deposits eliminated by subsequent impacts?
AB  - STR-based individualisation of biological deposits on bullets after perforation
      of tissue, can identify the person injured or killed by a particular bullet and
      comparison with the firearms used can identify the weapon and thus possibly the
      person who did the shooting. In this study, the effect of subsequent impacts on
      intermediate targets such as loss of cells was investigated by amplification of
      mitochondrial (mt) DNA. Bovine tissue was perforated and the 9 mm Luger FMJ
      bullets were recovered from the bullet collector. The mt cytochrome-b (cyt-b)
      gene could be amplified by the polymerase chain reaction (PCR) from 14 out of 15
      bullets. Examination with a scanning electron microscope (SEM) and an energy
      dispersive X-ray spectrometer (EDS) demonstrated the presence of minute dried
      tissue deposits on all bullets (n = 10) but was not able to establish
      preferential locations. In a series of 25 gunshots, various intermediate targets
      (glass, wood, car metal, gypsum board, asphalt) were perforated/impacted
      following perforation of tissue and the cyt-b gene could be typed from all
      bullets. It is concluded that subsequent impacts on intermediate targets do not
      eliminate enough biological deposits to render DNA analysis impossible and that
      the amplification of mtDNA is a useful additional method.

PMID- 11508801
TI  - The cloven hoof in legal medicine.
AB  - The injury of a horse's leg needed to be investigated to answer the question
      whether the fracture had been caused by an accident or by intentional
      manipulation. By toxicology and using scanning electron microscopy with an energy
      dispersive X-ray spectrometer (SEM-EDX) the suspicion obtained by morphology
      could be confirmed. Toxicologically a short term anaesthetic was found, and by
      EDX ferric oxide particles could be detected in the wound indicating that the
      injury was caused by a sharp pointed metallic instrument and not as stated by the
      owner by a wooden bar. As the result of the interdisciplinary investigation using
      modern techniques, there is no doubt that the owner attempted to fraudulently
      claim on an insurance policy.

PMID- 11508802
TI  - Tibetan population data on the PCR-typed loci D16S539, D7S820, D13S317,
      HUMF13A01, FESFPS, vWA, HUMTH01, TPOX and CSF1PO.
AB  - Frequency data for nine tetrameric short tandem repeat loci (D16S539, D7S820,
      D13S317, HUMF13A01, FESFPS, vWA, HUMTH01, TPOX and CSF1PO) were investigated in a
      population sample of 107 unrelated Tibetan individuals by using a multiplex
      polymerase chain reaction (PCR), followed by 4% polyacrylamide gel
      electrophoresis (PAGE) and silver staining. All loci met the Hardy-Weinberg
      expectations. The forensically relevant parameters were calculated. This is the
      first time that Chinese Tibetan population data on DNA loci have been reported
      that are of forensic importance.

PMID- 11508803
TI  - One fatal and seven non-fatal cases of 4-methylthioamphetamine (4-MTA)
      intoxication: clinico-pathological findings.
AB  - We present a case history involving one fatal and seven survived cases of
      intoxication with 4-methylthioamphetamine (4-MTA), also called para
      methylthioamphetamine (p-MTA) or methylthioamphetamine (MTA), a relatively new
      amphetamine analogue. Two of the seven survivors required a 24-h-period of
      observation in hospital. This report proves once again that the new amphetamine
      designer drugs are not without danger, as is thought by many young people. In
      addition, individually different subjective reactions are described. Finally, the
      medico-legal implications of new, as yet unregistered drugs are discussed.

PMID- 11508804
TI  - A review of 16 cases of honour killings in Jordan in 1995.
AB  - The purpose of the study was to determine the causes of death as reported in
      court files of the female victims of honour crimes, the Jordanian penal codes
      regarding crimes of honour, the evidence used in the sentencing of the
      defendants, the types of weapons used, the characteristics of the physical
      assaults on the victims and the sentencing of the offenders. A retrospective
      study of crimes of honour in Jordan was conducted, and the 16 homicide cases
      considered to be crimes of honour were reviewed. The autopsy reports of the
      victims provided information on the physical condition of the victims, including
      the type and severity of injuries. In over 60% of the honour crime cases,
      multiple gunshot wounds were the direct cause of death. In cases where the victim
      was a single pregnant female, the offender was acquitted of murder or received a
      reduced sentence. The majority of murders were committed by the brother of the
      victim and the length of sentence received by the offender varied from no
      sentence to life with hard labour. Offenders who received the harshest punishment
      were those whose victims married without the family consent.

PMID- 11508805
TI  - 13C spin-lattice relaxation in natural diamond: Zeeman relaxation in fields of
      500 to 5000 G at 300 K due to fixed paramagnetic nitrogen defects.
AB  - 13C Spin-lattice relaxation (SLR) times in the laboratory frame have been
      measured at room temperature as a function of field in the range of 500 to 5000 G
      on two natural type 1b and 1a diamonds after dynamic nuclear polarization. Each
      of the diamonds contains two types of fixed paramagnetic centers with overlapping
      inhomogeneous electron paramagnetic resonance (EPR) lines. EPR techniques have
      been employed to identify these defects and to determine their concentrations and
      relaxation times at X-band. Three different nuclear SLR paths, namely that due to
      electron SLR and two types of three spin processes, are discussed. The one three
      spin process (TSP) (type 1) involves a simultaneous transition of two electron
      spins belonging to the same hyperfine EPR line and a 13C spin while the other
      process (type 2) involves two electron spins belonging to different hyperfine EPR
      lines and a 13C spin. It is shown that the thermal contact between the 13C
      nuclear Zeeman and electron dipole-dipole interaction reservoirs decreases with
      an increase in field intensity, thus forming a bottleneck in the 13C relaxation
      path due to the type 1 TSP. The contribution of TSP of type 1 dominates that due
      to electron SLR and the type 2 TSP in relaxing the 13C nuclei in type lb diamond
      from about 1200 to 5000 G, while for type 1a diamond it dominates from 500 up to
      about 2200 G. In type 1a diamond over the range 2200 to 5000 G it seems that the
      type 2 TSP, which involves electrons of neighboring P2 hyperfine lines, dominates
      that of electron spin-lattice and the type 1 TSP. Over the range 500 to about
      1200 G, a field-dependent electron SLR mechanism associated with N3 centers
      appears to dominate the 13C SLR.

PMID- 11508806
TI  - Filtering of spinning sidebands in 1D MAS NMR spectra.
AB  - Spinning sidebands (SSBs) in the MAS NMR spectrum of a polycrystalline solid are
      related to the principal values of the chemical shift or quadrupole coupling
      tensors. At present, 2D methods are widely used to sort out the SSBs for each
      isotropic peak. Here a simple and efficient method for separating the SSBs in 1D
      MAS NMR spectra is described. It is based on finding the optimal spinning rate
      with a mathematical algorithm and subsequently treating the spectra with
      filtering functions.

PMID- 11508807
TI  - Homonuclear vanadium-51 dipolar couplings in inorganic solids obtained via hahn
      spin echo decay NMR spectroscopy.
AB  - Dipolar dephasing of the magnetization following a Hahn spin echo pulse sequence
      potentially provides a quantitative means for determining the dipolar second
      moment in solids. In this work, the possibility of employing Hahn spin echo decay
      spectroscopy to obtain quantitative 51V-51V dipolar second moments is explored.
      Theoretical spin echo response curves are compared to experimental ones for a
      collection of crystalline vanadium-containing compounds. This work suggests that
      51V dipolar second moments can be obtained by selectively exciting the central m
      = 1/2 --> -1/2 by a Hahn echo sequence for vanadate compounds with line
      broadening no greater than approximately 220 ppm. For vanadates with greater
      broadening of the central transition due to chemical shift, second-order
      quadrupolar, and dipolar interactions, off-resonance effects lead to an
      oscillatory time dependence of the spin echo. Experimentally determined second
      moments of the normalized echo decay intensities lie within 10-33% of the
      calculated values if the second moments are extrapolated to zero evolution time
      due to the time scale dependence of spin exchange among neighboring vanadium
      nuclei. Alternatively, the second moments can be obtained to within 10-25% of the
      calculated values if the broadening of the central transition due to chemical
      shift and second-order quadrupolar effects can be estimated.

PMID- 11508808
TI  - An optimal strategy for recovering the deuterium (2H) quadrupolar interaction
      under magic-angle spinning NMR.
AB  - By exploiting the homology in the form of the truncated high-field homonuclear
      dipole-dipole and quadrupole coupling Hamiltonians, we have previously
      demonstrated that a simple adaptation of a rotor-synchronized pulse sequence
      (DRAMA) used for the recovery of dipole-dipole couplings can also be used to
      resurrect quadrupole couplings (QUADRAMA). In the canonical implementation of
      these recovery pulse sequences, the couplings are not significantly scaled down
      from their static sample values. While such minimal scaling is of course
      desirable in the recovery of typical homonuclear dipolar couplings (< or =2 kHz)
      and small quadrupole couplings, it is clearly not ideal for the recovery of the
      much larger quadrupole couplings (20-200 kHz) often encountered in solid-state 2H
      NMR. In such a case, some prior knowledge of the order of magnitude of the
      coupling is required to optimize the experimental conditions for QUADRAMA. In
      order to overcome this drawback, in this study, we have developed a general and
      optimized strategy for implementing the QUADRAMA technique which does not require
      any knowledge of the size of the coupling vQ. Experimental tests of the optimized
      protocol demonstrate that by judicious choices of a combination of scaling
      factors and recoupling times, 2H quadrupole couplings ranging over an order of
      magnitude from 3 to 42 kHz can be measured. Since this optimized protocol can
      reliably be used to recover couplings over a broad range, it expands the range of
      systems accessible to study by 2H NMR into a realm where static sample NMR and
      simple MAS NMR may fail.

PMID- 11508809
TI  - Boron neutron capture therapy: effects of split dose and overall treatment time.
AB  - New clinical protocols are being developed that will entail the administration of
      considerably higher doses of the boron delivery agent boronophenylalanine (BPA)
      than those in current clinical use. Fractionation (2 or 4 fractions) of BPA
      mediated boron neutron capture therapy (BNCT) is also under consideration at some
      clinical centres. Given the considerably higher infusion volumes that will be
      entailed in the delivery of BPA in the new high dosage protocols, there will be a
      requirement to extend the gap between fractions to 2 or more days. In order to
      assess the effects of a 2 fraction protocol on the therapeutic efficacy of BPA
      mediated BNCT, a series of split dose irradiations (two equal fractions) were
      undertaken using the rat intracranially implanted 9L gliosarcoma model. A single
      dose exposure to BPA mediated BNCT of 3.0 Gy resulted in long term survival
      levels of 50%. Survival levels increased to 71% and 77% with a 3 and 5 day gap
      between dose fractions (two equal fractions), respectively, using the same total
      dose. A further increase in the time interval between dose fractions to 7 days
      resulted in a reduction in survival to 36%. However, there was no significant
      difference between the single dose and the 3, 5 and 7 day survival data (P > 0.1)
      The difference between the 5 and 7 day split dose survival data was of border
      line significance (P = 0.05). It is anticipated that mucositis, could become a
      potential problem in future BNCT clinical protocols involving higher doses,
      larger field sizes or multiple fields. The potential sparing of the oral mucosa,
      due to repopulation during the interval between the two fractions, was
      investigated using a series of split dose BPA mediated BNC irradiations. The
      ventral surface of the rat tongue was utilised as a model for oral mucosa. The
      ED50 (50% incidence) values for the ulceration end point were 3.0+/-0.1, 3.2+/
      0.1, 3.0+/-0.1 and 3.6+/-0.1 Gy, for 3, 5, 7 and 9 day splits between doses,
      respectively. It is evident from this data that there were no significant changes
      in the ED50 (p < 0.001) until the 9 day dose split, when the ED50 value was 20%
      higher than the ED50 value after a 7 day split. It was concluded that the two
      fraction BNCT protocol, with dose splits of up to 5 days, did not diminish the
      therapeutic response of the rat 9L gliosarcoma, when compared with a single dose
      BNCT protocol. Tolerance of the oral mucosa to BNC irradiation was not increased
      until there was a 9 day gap between fractions. However, the beneficial effects of
      dose sparing at this time interval between doses, would probably be counteracted
      by a reduction in the therapeutic effectiveness of the BNCT modality, due to
      repopulation of tumour clonogens between doses.

PMID- 11508810
TI  - Biodistribution of copper carboranyltetraphenylporphyrins in rodents bearing an
      isogeneic or human neoplasm.
AB  - The biodistributions of carborane-containing copper porphyrins, CuTCP and CuTCPH,
      have been studied previously in mice bearing subcutaneously implanted mammary
      carcinomas. We now report biodistributions of those porphyrins in Fischer 344
      rats bearing intracranial and/or multiple subcutaneous isogeneic 9L gliosarcomas
      (9LGS). The porphyrin was given either by i.v. infusion or by multiple i.p.
      injections. When 190 mg CuTCPH/kg body weight was given to the rats by i.v.
      infusion, median tissue boron concentrations (microg/g) 3 days after the end of
      infusion were: 64 in subcutaneous tumor, 13 in intracranial tumor, 1 in blood and
      3 in brain. When 450 mg CuTCPH/kg body weight was given to the rats by serial
      i.p. injections, the median concentrations (microg B/g) 4 days after the last
      injection were: 117 in subcutaneous tumor, 50 in intracranial tumor, 4 in blood,
      and 4 in brain. CuTCPH biodistribution was also studied in xenografts of the
      human malignant gliomas U87 and U373, and of the murine EMT-6 mammary carcinoma
      and the rat 9LGS, each grown subcutaneously in mice with severe combined
      immunodeficiency (SCIDs). In SCIDs, median boron concentrations (microg/g) 2 days
      after the last s.c. injection of a total of 190 mg CuTCPH/kg body weight were:
      251 in U373, 33 in U87, <0.6 in blood and <0.5 in brain. Because there were such
      high boron levels in the U373, and because xenografted U373 is similar to
      spontaneous intracerebral human glioblastoma multiforme (GBM) microscopically,
      CuTCPH could prove useful as a boron carrier for boron neutron-capture therapy
      (BNCT) of GBM and of other human malignant gliomas.

PMID- 11508811
TI  - Identification of uncommon chromosomal aberrations in the neuroglioma cell line
      H4 by spectral karyotyping.
AB  - To elucidate the reasons why mRNA expression of the LGI1 candidate tumor
      suppressor gene was severely reduced in the glioma-derived cell line H4, as
      demonstrated in a previous study, we performed a cytogenetic analysis of this
      cell line using conventional methods and fluorescence in situ hybridization
      (FISH) techniques [spectral karyotyping (SKY), interphase- and chromosome FISH of
      metaphases (I- and C-FISH)]. Cell line H4 is monoclonal and near triploid (+/
      3n). SKY enabled us to detect 24 structural aberrations: unbalanced
      translocations, n = 12; deletions, n = 10; insertion, n = 1; duplication, n = 1.
      The results were confirmed by I- and C-FISH analysis using chromosome-specific
      paints, centromer-specific probes and locus-specific probes for p53, PTEN/MMAC1,
      LGI1, Cyclin D1, EGR1, ETV6/TEL, AML1, and the genomic region 13q14.3 containing
      the Rb locus. We found loss of one copy of p53 as well as of one copy of Rb.
      Complete loss of PTEN/MMAC1 was detected, while all copies of LGI1 and Cyclin D1
      were preserved. Interestingly, there was a gain of ETV6/TEL and EGR1, which were
      each present in quadruplicate. Additionally, the AML1 locus revealed mosaicism of
      cells with three and four copies, respectively. Additionally, a 5q-chromosome
      [del(5)(q13q33)] was found, which is one of the common features in hematological
      malignancies, and der(12)t(1;12) was found, suggesting that there might be an
      additional ETV6/TEL fusion protein. The combination of SKY, I- and C-FISH
      demonstrates that the neuroglioma cell line H4 harbors cytogenetic aberrations
      that are reported to occur in glioma-derived cell lines and additional
      chromosomal aberrations that have so far not been reported to occur in these cell
      lines. The complex aberrant karyotype and possibly generation of transcription
      factors by fusion proteins might be reasons for the impaired mRNA expression of
      the LGI1 candidate tumor-suppressor gene in cell line H4.

PMID- 11508813
TI  - Bone metastases from secondary glioblastoma multiforme: a case report.
AB  - Extraneural metastases of glioblastoma multiforme (GBM) are a relatively rare
      occurrence which usually manifest after de novo GBM. We report a case of a
      patient with an oligodendroastrocytoma who developed over a period of 12 years
      malignant progression to glioblastoma followed by multiple cytologically
      confirmed bone metastases. No 1p deletions were detected in the original tumour.
      GBM cells disclosed the EGFr(+) and p53(-) immunophenotype more characteristic of
      a primary GBM.

PMID- 11508812
TI  - Expression of bcl-2, bax and bcl-xl in human gliomas: a re-appraisal.
AB  - We have analyzed the expression of the anti-apoptotic proteins bcl-2, bcl-xl and
      that of bax, a pro-apoptotic protein, in human WHO grade II astrocytomas (LGA)
      and WHO grade IV glioblastoma multiforme (GBM). Tumors were obtained immediately
      after surgical resection and were analyzed by immunohistochemistry (IHC), laser
      confocal microscopy (LCM) and immunoblots. Both IHC and immunoblot analysis
      indicated that the expression of bcl-xl was not significantly different between
      LGA and GBM. IHC indicated that the expression of bcl-2 was inversely correlated
      to the grade of the tumors (i.e more cells were bcl-2 positive in LGA than in
      GBM) while the expression of bax was unaffected by the grade of the tumor. In
      contrast, immunoblots revealed a parallel increase in the expression of bcl-2 and
      bax from the low to high grade tumor, suggesting a co-regulation of the
      expression of these two proteins during tumoral progression. Confocal analyses
      provide us with another possible level of complexicity in the regulation of
      apoptosis in these tumors, as these markers exhibited different subcellular
      localizations: bcl-2 was strictly associated with mitochondria and bcl-xl was
      present in both cytosolic and mitochondrial compartments while bax was found
      essentially in the cytosol of the tumoral cells. Taken together, our data suggest
      that the role of bcl-2 related proteins could be regulated at different levels in
      human astrocytomas (expression, subcellular localization, antigen exposure ...)
      which should be studied by different techniques.

PMID- 11508814
TI  - Fotemustine combined with procarbazine in recurrent malignant gliomas: a phase I
      study with evaluation of lymphocyte 06-alkylguanine-DNA alkyltransferase
      activity.
AB  - The aims of this phase I study in patients with recurrent malignant gliomas were
      to determine the maximum tolerated dose (MTD) and toxicity profile of fotemustine
      when combined with a fixed dose of procarbazine (PCZ), and to evaluate the extent
      of O6-alkylguanine-DNA alkyltransferase (ATase) depletion in circulating
      lymphocytes during treatment. Sixteen patients received an induction cycle
      consisting of 100 mg/day oral PCZ for 12 consecutive days and a 1-h intravenous
      infusion of fotemustine given 4 h after PCZ on days 5 and 12 at escalated doses
      (50, 75, 100 and 125 mg/m2/day). After a 6-week rest period, a maximum of 4
      maintenance cycles (PCZ 300 mg/day, 4 days; fotemustine, day 4) was given every 4
      weeks. ATase activity was measured on days 1, 5 and 12 over 4 h after PCZ intake.
      Fifteen patients had previously received at least one nitrosourea-based
      chemotherapy, associated with PCZ in 12 cases. The MTD of fotemustine was 125
      mg/m2 (days 5 and 12) with myelosuppression as the dose limiting toxicity (DLT).
      At this dose level, half of patients experienced grade 3 anemia, neutropenia or
      thrombopenia. No extra-hematological DLT was observed. No significant depletion
      of ATase activity by PCZ was evidenced. One partial response and 7 stable
      diseases were obtained leading to a disease control rate of 50%. The median times
      to progression and survival were 2.6 and 9.7 months, respectively. This combined
      regimen of PCZ and fotemustine was well tolerated with a good disease control
      rate in heavily pretreated glioma patients and merits further investigation in
      phase II studies.

PMID- 11508815
TI  - Malignant fibrous histiocytoma presenting as an intraventricular mass five years
      after incidental detection of a mass lesion.
AB  - Malignant fibrous histiocytoma is a rare intracranial neoplasm. It usually
      presents as a meningeal mass but occurs also intraaxially. Few information is
      available on cellular origin, premalignant histologic stages and time course of
      malignant transformation. We report a case of a primary intraventricular
      malignant fibrous histiocytoma in a patient who five years prior to clinical
      manifestation of the malignancy was found to have an intraventricular mass with
      benign CT characteristics.

PMID- 11508816
TI  - Selection of eligible patients with supratentorial glioblastoma multiforme for
      gross total resection.
AB  - The purpose of this study is to clarify whether gross total tumor resection can
      prolong the survival in adult patients with supratentorial glioblastoma
      multiforme (GBM), and to clarify what subset of these patients obtains a survival
      advantage by gross total tumor resection without postoperative neurological
      deterioration. Eighty-two adult patients with supratentorial GBM were
      retrospectively reviewed. Overall, the median survival time was 13 months, and
      the 1- and 2-year survival rates were 53.7% and 14.6%, respectively. In a
      univariate analysis for survival rate by log-rank test, age (< 40 years),
      Karnofsky performance scale (KPS) score (70-100%) and extent of surgery (gross
      total resection) were revealed to be significant good prognostic factors. A Cox
      proportional hazard multivariate regression analysis confirmed that the KPS and
      extent of surgery were independent, significant good prognostic factors. Nine
      patients (11%) suffered postoperative neurological deterioration. A topographical
      GBM staging system (Stages I, II and III) with the integration of tumor location,
      size and eloquence of adjacent brain based on MRI (for explanation of Stages see
      text) was originally proposed. In Stage I, gross total resection had a strong
      tendency toward a better prognostic factor in a univariate analysis and was
      revealed to be a significant independent good prognostic factor in a multivariate
      analysis. In also Stage II, the survival of patients who underwent gross total
      resection was better than that of patients with less than gross total resection,
      although not significant. In Stage III, there were no patients who underwent
      gross total tumor resection. Risk probabilities of postoperative neurological
      deterioration, overall, were 0%, 22.2%, and 20% in Stages I, II, and III,
      respectively, and those after gross total resection were 0% and 16.7% in Stages I
      and II, respectively. Although gross total tumor resection is associated with
      prolongation of the survival time of patients with GBM, the risk of postoperative
      neurological deficit increases with radical tumor resection. To select an
      eligible subset of patients that benefit in survival from gross total tumor
      resection without postoperative risk, the following surgical policy for GBM
      resection is suggested. GBM in Stage I should be resected as radically as
      possible. Regarding Stage II, risky surgical resection extending to the area
      adjacent to the critical zone should be avoided and more meticulous and careful
      surgical planning is needed than that in Stage I. In Stage III, radical gross
      total tumor resection is not recommended at present.

PMID- 11508817
TI  - Primary Ewing's sarcoma/peripheral primitive neuroectodermal tumor at the vertex
      of the skull with elevated serum carcinoembryonic antigen: case report.
AB  - A primary Ewing's sarcoma arising in the skull is relatively rare. Although a
      small number of case reports noted elevated carcinoembryonic antigen (CEA) in
      patients with primary central nervous system (CNS) neoplasms, there is no report
      of Ewing's sarcoma/peripheral primitive neuroectodermal tumor (PNET) with
      elevated serum levels of CEA. A 7-year-old boy who had episodes of headache and
      vomiting had noticed a solid mass in the vertex of the head. Imaging studies
      revealed a large intra- and extracranial tumor at the vertex of the skull.
      Hematological examination demonstrated high serum levels of CEA: 91.09 ng/ml. The
      patient initially underwent an embolization of the bilateral middle meningeal
      arteries with Gelfoam particles. One week later, the patient was operated on and
      a subtotal resection of the tumor was performed. On histopathological and
      molecular genetic examination, the tumor was diagnosed as a Ewing's
      sarcoma/peripheral PNET. Immunohistochemical study showed strongly positive
      staining for CEA in the tumor cells. The serum level of CEA was normalized at
      0.83 ng/ml after the tumor was removed and the boy underwent radiotherapy and 3
      courses of chemotherapy. This is the first reported case of a primary Ewing's
      sarcoma/peripheral PNET at the vertex of the skull with elevated serum CEA.

PMID- 11508819
TI  - Are the ALTERNATIVES in pharmacology and toxicology real alternatives?

PMID- 11508818
TI  - Primary meningeal sarcomas in two children.
AB  - Primary meningeal sarcomas are rare but highly aggressive tumors predominantly
      affecting children. The clinical course, imaging characteristics and
      histopathological features of meningeal sarcomas in two pediatric patients are
      presented. Furthermore, we critically discuss the new WHO classification of these
      entities comparing them to older descriptions. In a 6-year-old girl, a cranial
      computed tomography (CT) scan was performed, after a mild head trauma, showing a
      parieto-occipital hemorrhage. One month later, a circumscribed mass adhering to
      the meninges and with central areas of hemorrhage was evident on magnetic
      resonance imaging (MRI) scans. Brain biopsy revealed a polymorphocellular sarcoma
      originating from the leptomeninges and infiltrating the brain. In an 8-year-old
      girl, who presented with headaches and vomiting, several MRI-examinations were
      inconspicuous for nearly one year until the latest MR-scan revealed a diffuse
      contrast enhancement of the leptomeninges of the whole brain and spinal canal.
      After open biopsy, primary leptomeningeal sarcomatosis was diagnosed. Although CT
      and MRI did not allow a specific diagnosis in both cases the exact visualization
      of the extent of the tumor and/or meningeal involvement was possible. Since there
      are no specific imaging criteria to differentiate meningeal sarcoma from other
      solid brain tumors or from other tumoral or inflammatory meningioses brain biopsy
      is indispensable. In order to avoid misinterpretations and delays of therapy,
      early open brain biopsy or surgical resection of the lesion is necessary in cases
      of unclear brain masses, especially of unclear meningeal processes. Due to the
      low number of cases published so far, the biological behavior and clinical
      management of this tumor entity still awaits further investigation.

PMID- 11508820
TI  - Fractal analysis of STM images of photochemical polymer of coniferyl alcohol.
AB  - Fractal analysis was applied to images of photochemical lignin polymer obtained
      using scanning tunneling microscope. We studied the polymer obtained in vitro by
      ionic mechanism through UV radiation--induced polymerization. The analysis showed
      the regularity of the lignin-like polymer at different levels of organization. At
      the 95% confidence level, there was no significant difference in the fractal
      dimension between images representing different organizational levels of
      photochemical lignin. That means that lignin produced in in vitro conditions by
      photochemical mechanism of synthesis, has a fractal structural organization. The
      obtained values of the fractal dimension are in good agreement with the
      theoretically predicted value for the polyaddition and polycondensation mechanism
      of polymerization, known as the bulk model.

PMID- 11508821
TI  - Thyrotropin-releasing hormone activates KCa channels in gastric smooth muscle
      cells via intracellular Ca2+ release.
AB  - Thyrotropin-releasing hormone (TRH) is released in high concentrations into
      gastric juice, but its direct effect on gastric smooth muscles has not been
      studied yet. We undertook studies on TRH effect on gastric smooth muscle using
      contraction and patch clamp methods. TRH was found to inhibit both acetylcholine-
      and BaCl2-induced contractions of gastric strips. TRH, applied to single cells,
      inhibited the voltage-dependent Ca2+ currents and activated the whole-cell K+
      currents. The TRH-induced changes in K+ currents and membrane potential were
      effectively abolished by inhibitors of either intracellular Ca2+ release channels
      or phospholipase C. Neither activators, nor blockers of protein kinase C could
      affect the action of TRH on K+ currents. In conclusion, TRH activates K+ channels
      via inositol-1,4,5-trisphosphate-induced release of Ca2+ in the direction to the
      plasma membrane, which in turn leads to stimulation of the Ca2+-sensitive K+
      conductance, membrane hyperpolarization and relaxation. The data imply that TRH
      may act physiologically as a local modulator of gastric smooth muscle tone.

PMID- 11508822
TI  - Neural network comparing two-rate-encoded inputs entering in parallel.
AB  - Presented computational model of a neural network is able to compare two regular
      input frequencies. The comparison is based on detection of inter-spike interval
      differences of the two frequencies. This detection is continuous and the network
      dynamically changes its output according to the changes in the input frequencies.
      The entire network is composed of biologically plausible parts. A combination of
      such simple comparators might be involved in the information processing in the
      central nervous system.

PMID- 11508823
TI  - Amylolytic enzymes: molecular aspects of their properties.
AB  - The present review describes the structural features of alpha-amylase, beta
      amylase and glucoamylase that are the best known amylolytic enzymes. Although
      they show similar function, i.e. catalysis of hydrolysis of alpha-glucosidic
      bonds in starch and related saccharides, they are quite different. alpha-Amylase
      is the alpha --> alpha retaining glycosidase (it uses the retaining mechanism),
      and beta-amylase together with glucoamylase are the alpha --> beta inverting
      glycosidases (they use the inverting mechanism). While beta-amylase and
      glucoamylase form their own families 14 and 15, respectively, in the sequence
      based classification of glycoside hydrolases, alpha-amylase belongs to a large
      clan of three families 13, 70 and 77 consisting of almost 30 different
      specificities. Structurally both alpha-amylase and beta-amylase rank among the
      parallel (beta/alpha)8-barrel enzymes, glucoamylase adopts the helical
      (alpha/alpha)6-barrel fold. The catalytic (beta/alpha)8-barrels of alpha-amylase
      and beta-amylase differ from each other. The only common sequence-structural
      feature is the presence of the starch-binding domain responsible for the binding
      and ability to digest raw starch. It is, however, present in about 10% of
      amylases and behaves as an independent evolutionary module. A brief discussion on
      structure-function and structure-stability relationships of alpha-amylases and
      related enzymes is also provided.

PMID- 11508824
TI  - Gallamine triethiodide selectively blocks voltage-gated potassium channels in
      Ranvier nodes.
AB  - The effects of gallamine on ionic currents in single intact Ranvier nodes of the
      toad Xenopus were investigated. The following fully reversible effects were
      observed: 1. With a test concentration of 1 mmol/l the current-voltage relation
      of steady-state potassium currents, IK ss exhibited a complete block of IK ss up
      to about V = 110 mV; with stronger depolarisations the block was incomplete. The
      peak sodium currents, in contrast, were not affected. 2. At the same test
      concentration the potassium permeability constant PK was reduced by 92% from its
      normal value, while the sodium permeability constant PNa decreased by only 8%. 3.
      Concentration-response relations of the block of PK yielded an apparent
      dissociation constant of 30 micromol/l and a steepness parameter of unity. Patch
      clamp experiments on cloned Kv1.1, Kv1.2, Kv1.3 and Kv3.1 channels yielded
      apparent dissociation constants of 86, 19, >>100 and 121 micromol/l,
      respectively. Our findings show that gallamine is particularly well suited for
      separating potassium and sodium currents in axonal current ensembles. They also
      strongly suggest that potassium currents in Ranvier nodes of Xenopus are mainly
      carried by an ensemble of Kv1.1 and 1.2 channels.

PMID- 11508825
TI  - Apamin-sensitive nitric oxide- and ATP-mediated motor effects on the guinea pig
      small intestine.
AB  - The involvement of nitric oxide and ATP in both spontaneous and electrically
      induced nonadrenergic noncholinergic (NANC) motor activity with special interest
      in the apamin-sensitive mechanisms was studied in a guinea pig ileum model.
      Depending on the concentration (0.1 or 1 micromol/l), apamin, a blocker of the
      calcium-activated potassium channels and antagonist of ATP action, induced either
      TTX (0.1 micromol/l)-resistant increase in tone or contractions. SNP, a nitric
      oxide donor, applied cumulatively (0.1-100 micromol/l) evoked a concentration
      dependent relaxation, the EC50 value being 0.39 +/- 0.12 micromol/l. At
      concentrations of 0.1 or 1 micromol/l, apamin decreased the SNP effects and
      shifted the concentration-response curves for SNP to the right. The EC50 value
      for SNP in the presence of apamin at a concentration of 0.1 micromol/l increased
      to 59.34 +/- 36.53 micromol/l. ATP (1 or 50 micromol/l) induced TTX-resistant
      contractions. The effects of ATP were reduced by apamin (1 micromol/l). The
      contractile effect of ATP occurred in the presence of SNP. SNP provoked
      relaxation on the background of ATP. The NANC responses to electrical stimulation
      (0.8 ms, 40 V, 2 or 20 Hz, 20 s) consisted of an initial relaxation phase
      followed by a phase of contractions, twitch-like and tonic. L-NNA (0.5 mmol/l),
      an inhibitor of nitric oxide syntheses, abolished the relaxation phase. L
      arginine (0.5 mmol/l) restored it. Apamin (0.1 or 1 micromol/l) completely
      eliminated the relaxation phase and concentration-dependently inhibited the tonic
      contraction of the phase of contractions. The present findings indicate that the
      apamin-sensitive nitric oxide-evoked relaxation could be realized by calcium
      activated potassium channels and that the apamin-sensitive ATP-induced
      contraction is mediated via contraction-producing P2 purinoceptors.

PMID- 11508826
TI  - Review: molecular thyroidology.
AB  - Novel disorders involving aberrations of the hypothalamic-pituitary-thyroid gland
      thyroid hormone axis have been described in the last 5 to 10 years. The following
      topics are addressed: molecular mutations causing central hypothyroidism
      (isolated autosomal recessive TRH deficiency; autosomal recessive TRH-receptor
      inactivating mutations; TSH beta-subunit bio-inactivating mutations; Pit-1
      mutations; Prop1 mutations; high molecular weight bio-inactive TSH); defects in
      response to TSH (mutations in the TSH receptor: TSH receptor gain-of-function
      mutations; TSH receptor loss-of-function mutations); defects in thyroid gland
      formation: transcription factor mutations (TTF-2 and Pax8); defects in peripheral
      thyroid hormone metabolism (defective intrapituitary conversion of T4 to T3;
      hemangioma consumption of thyroid hormone); and defects in tissue response to
      thyroid hormone (generalized thyroid hormone resistance, selective pituitary
      thyroid hormone resistance). While molecular diagnosis of such conditions is
      rarely indicated for clinical management, knowledge of the molecular mechanisms
      of these diseases can greatly enhance the clinical laboratory scientist's ability
      to advise clinicians about appropriate thyroid testing and to interpret the
      complex and sometimes confusing results of thyroid function tests.

PMID- 11508827
TI  - Nuclear localization of thyroid transcription factor-1 correlates with serum
      thyrotropin activity and may be increased in differentiated thyroid carcinomas
      with aggressive clinical course.
AB  - Thyroid transcription factor 1 (TTF-1) is essential for thyroid differentiation
      and regulates expression of thyroglobulin, thyroid peroxidase, sodium/iodide
      symporter, and thyrotropin receptor (TSH-R) genes. Because thyrotropin (TSH)
      upregulates these same genes, we hypothesized TSH-R activation might increase TTF
      1 and that TTF-1 might be differentially expressed in benign and malignant
      thyroid disease. TTF-1 expression and sub-cellular localization were determined
      by immunohistochemistry in 62 thyroid carcinomas, 15 benign lesions, and 2 normal
      thyroids. Nuclear TTF-1 was detected in benign (77%) and malignant lesions (69%),
      with similar intensity in both (1.1+/-0.19 versus 1.0+/-0.10). Nuclear TTF-1
      staining correlated with the effective serum TSH level (p = 0.02) and patient age
      (p < 0.05). Nuclear TTF-1 was detected in 35 papillary thyroid carcinomas (PTC),
      of which 23% developed recurrent or persistent disease, and was absent from 18
      PTC, of which only 6% recurred (p = 0.06). We conclude that nuclear TTF-1
      correlates with serum TSH activity, increases with age, and may be increased in
      persistent or recurrent PTC.

PMID- 11508828
TI  - Serum anti-p53 autoantibodies in patients with type 1 diabetes.
AB  - The presence of antibodies reacting with the p53 tumor suppressor protein has
      been described in patients with some autoimmune disorders. In this study we
      looked for serum anti-p53 antibodies in 64 patients with autoimmune type 1
      diabetes mellitus within 4 mo of diagnosis. The presence of anti-p53 antibodies
      was observed in 6/64 (9.4%) subjects with type 1 diabetes, and in 1/44 (2.3%)
      subjects with other organ-specific autoimmune diseases (18 primary biliary
      cirrhosis, 10 autoimmune hepatitis, 16 thyroid diseases), but in none of 45
      control subjects. No relationship was found between antibodies directed against
      islet- and non-islet-specific antigens and anti-p53 antibodies. These findings
      support a possible role for p53 in some autoimmune disorders.

PMID- 11508829
TI  - Abnormal chromatographic patterns of porphyrins in urine.
AB  - Urine is the most frequent specimen used in the initial evaluation of adult
      patients who present with photosensitivity. When urine porphyrins are abnormal,
      characterization of the chromatogram is facilitated by calculation of
      uroporphyrin-to-heptacarboxylate porphyrin (uro/hepta) and uroporphyrin-to
      isocoproporphyrin (uro/iso) ratios. The most frequent abnormal pattern, and that
      most consistent with porphyria cutanea tarda (PCT), is an uro/hepta ratio < or
      =2.0 and an uro/iso ratio < or =18. When the uro/hepta or uro/iso ratios are less
      consistent with PCT, other less common porphyrin disorders should be considered.
      These include variegate porphyria, coproporphyria with manifestations of
      photosensitivity only, adult onset congenital porphyria, mixed porphyrias, and
      other less frequent porphyrin disorders. After initial evaluation, the diagnosis
      should ideally be confirmed by additional testing of blood and fecal specimens.
      Most attacks of the acute porphyrias are associated with a uro/hepta ratio >4,
      and can be confirmed by an elevated urine porphobilinogen concentration.

PMID- 11508830
TI  - A practical approach to glomerular filtration rate measurements: creatinine
      clearance estimation using cimetidine.
AB  - Determination of creatinine clearance (Ccr) is not a reliable indicator of
      glomerular filtration rate (GFR), owing to tubular secretion of creatinine. It
      has been reported that Ccr measurements can approximate true GFR after cimetidine
      (Ci) administration. In this study, GFR was estimated by Cockcroft and Gault's
      equation (C(C-G)) based on measurement of plasma creatinine, and Ccr was
      determined by the standard clearance equation using 4- and 24-hr urine samples
      (Ccr4 and Ccr24, respectively) in 17 patients and 10 healthy controls. After
      cimetidine administration (800 mg, 3 times daily), GFR values were recalculated
      at the same time periods (C(CiC-G), CcrCi4 and CcrCi24, respectively). The
      results were all compared to those obtained by the 99mTc-DTPA protein-free double
      sample method (C(DTPA)), which is a reference method for GFR determination. The
      coefficient of variation (CV%) for Ccr24/C(DTPA) was high before cimetidine
      administration; Ccr24 and CcrCi24 values were significantly different from
      C(DTPA) (CV 23.1%, Ccr24/C(DTPA) = 1.17, p 0.005; and CV 14.1%, CcrCi24/C(DTPA) =
      0.92, p 0.006, respectively). Ccr4 values obtained before cimetidine ingestion
      showed large variation and were significantly different from C(DTPA) (CV 15.5%,
      Ccr4/C(DTPA) = 1.11, p 0.001). CcrCi4 values after cimetidine were similar to
      CDTPA (CV 6.9%, CcrCi4/C(DTPA) = 1.01, p 0.28). C(C-G) estimates were higher
      before cimetidine intake (CV 12.4%, C(C-G)/C(DTPA) = 1.21, p <0.001), whereas
      C(CiC-G) values were not significantly different from C(DTPA) values (CV 7.0%,
      C(CiC-G)/C(DTPA) = 1.01, p 0.67). This study shows that GFR estimations by C(C
      G), Ccr4, Ccr24, or CcrCi24 are insufficiently reliable. On the other hand, C(CiC
      G) and CcrCi4 results are acceptable for true GFR estimations.

PMID- 11508831
TI  - Suppression of polyclonal immunoglobulin production by M-proteins shows isotype
      specificity.
AB  - Monoclonal gammopathies are B cell neoplasms that are characterized by the
      presence of monoclonal immunoglobulins (M-proteins) in the serum. By an unknown
      mechanism, the normal polyclonal immunoglobulin levels are frequently reduced in
      sera of these patients. To assess the role of M-protein isotype in this effect,
      we used serum protein electrophoresis to quantitate monoclonal and polyclonal
      immunoglobulins in patients and we used serum immunofixation electrophoresis to
      determine their M-protein isotype. When divided into populations of 30 patients
      with IgG M-proteins (mean 2.5 g/dl) and 19 patients with IgM or IgA M-proteins
      (mean 2.6 g/dl), the mean polyclonal immunoglobulin level was significantly lower
      in the IgG M-protein population (0.4 g/dl) than the IgM/IgA population (0.8
      g/dl). Patients with IgG M-proteins also had significantly lower polyclonal
      immunoglobulin levels when compared separately with the patients with either IgA
      or IgM paraproteins. Since the polyclonal immunoglobulin fraction is comprised
      mostly of IgG, these results give the first direct indication that IgG M-proteins
      have a greater suppressive effect on polyclonal IgG levels than do M-proteins of
      other isotypes. These findings suggest that an isotype-specific feedback
      mechanism could be involved in the normal regulation of serum IgG levels.

PMID- 11508832
TI  - Comparison of the BACTEC MGIT 960 and BACTEC 460TB systems for detection of
      mycobacteria in clinical specimens.
AB  - The reliability of the Mycobacteria Growth Indicator Tube (MGIT) 960 system for
      rapid detection of mycobacteria in clinical specimens was evaluated and compared
      to the radiometric method (BACTEC 460TB) and to mycobacterial culture on
      Lowenstein-Jensen (LJ) medium. Clinical specimens (n = 590) were tested without
      selection. A total of 121 (20.5%) isolates of mycobacteria were recovered; 98
      (81.0%) of them were recovered with the BACTEC 460TB system, 86 (71.1%) were
      recovered with the BACTEC MGIT 960 system, and 55 (45.5%) were recovered with LJ
      medium (MGIT 960 versus BACTEC 640TB, p >0.05; MGIT 960 or BACTEC 460TB versus
      LJ, p <0.001). The mean time to detection (TTD) was 18 da for BACTEC 460 TB, and
      13 da for BACTEC MGIT 960. The mean time to detection in each system, based upon
      data where both systems were culture positive, was significantly different (16.6
      da for BACTEC 460TB and 13 da for BACTEC MGIT 960, p<0.001). The contamination
      rate of the BACTEC MGIT 960 system was 13.2%, which was intermediate between the
      BACTEC 460TB system (11.7%) and the LJ medium (14.7%). These data indicate that
      the fully automated MGIT 960 system is an accurate, non-radiometric alternative
      to the BACTEC 460TB method for rapid detection of mycobacteria in a clinical
      setting.

PMID- 11508833
TI  - Ultrastructure of the periductal area of comedo carcinoma in situ of the breast.
AB  - We have previously shown that the different biological natures of comedo ductal
      carcinoma in situ (DCIS) and non-comedo DCIS may, in part, be explained by the
      different expression patterns of tenascin, a large extracellular matrix protein,
      as observed by immunohistochemical studies. In the present study, we compared 8
      cases of comedo DCIS with 5 cases of non-comedo DCIS by ultrastructural analysis,
      focusing on the myoepithelium, basal lamina, and tenascin-positive extracellular
      periductal stromal matrix. Our observations show that the comedo type DCIS
      frequently has an altered basal lamina, a looser and more disorganized
      collagenous matrix, and a general increase in stromal cellularity, including
      fibroblasts, lymphocytes, histiocytes and small blood vessels. In addition, in
      comedo DCIS, the lateral intercellular spaces between large myoepithelial cells
      that border the basal lamina are often expanded, compared to those of non-comedo
      DCIS. These results identify structural characteristics of comedo DCIS that may
      play a role in its greater preinvasive potential. They may also provide a
      structural basis for the different strategies that are needed for for clinical
      management of comedo DCIS, compared to non-comedo DCIS.

PMID- 11508834
TI  - Papillary fibroelastoma of the heart: report of two cases and review of the
      literature.
AB  - Papillary fibroelastoma is the most common primary cardiac valvular tumor.
      Historically, papillary fibroelastoma was an incidental autopsy finding, deemed
      to have no clinical significance. More recently, reports of symptomatic cases of
      papillary fibroelastoma with complications such as myocardial infarction and
      stroke have led papillary fibroelastoma to be considered a potentially dangerous
      lesion. We report 2 cases of symptomatic papillary fibroelastoma, both of which
      presented with a stroke. Both patients underwent uneventful open-heart surgery.
      The literature is reviewed, with a compilation of 79 cases.

PMID- 11508835
TI  - Conformational study of proteins by SAXS and EDXD: the case of trypsin and
      trypsinogen.
AB  - The radius of gyration (Rg) of bovine trypsinogen and beta-trypsin was measured
      by an energy-dispersive X-ray technique (EDXD) and by small-angle X-ray
      scattering (SAXS), under different solvent conditions. Both techniques gave
      superimposable results. The experimental evidence demonstrated that: (1) no
      structural modifications and/or damage occurred during the data acquisition by
      EDXD; (2) at pH 4 the active enzyme has one class of chloride binding sites in
      common with the zymogen, whereas the latter protease shows an additional class
      able to reverse the effects on Rg induced by chloride at low concentration; and
      (3) the pH profile of the Rg of both proteases does not resemble at all the pH
      effect on beta-trypsin activity, a result in line with the finding that the
      electrical potentials induced by surface charge are small in absolute magnitude
      and produce no gradient across the active site.

PMID- 11508836
TI  - Structural heterogeneity of blue copper proteins: an EPR study of amicyanin and
      of wild-type and Cys3Ala/Cys26Ala mutant azurin.
AB  - A comparative investigation of the effects of cooling rate and solvent
      physicochemical properties on the structural heterogeneity of wild-type and
      disulfide bond depleted azurin (Cys3Ala/Cys26Ala) and of amicyanin has been
      performed by EPR spectroscopy and computer simulation. By describing the spectral
      features of the EPR spectra in terms of Gaussian distributions of the components
      of the g and A tensors of the spin Hamiltonian, we have shown that either the
      cooling rate or the solvent composition affect the structural heterogeneity of
      the proteins. Such a heterogeneity has been quantified by the standard deviations
      sigmag and sigmaA of the parallel components of the axially symmetric tensors. In
      particular, both parameters become smaller after the slow cooling cycle; such a
      reduction is more significant when glycerol is added as cosolvent to the protein
      solutions. The comparison of the deltag and sigmaA values found, for the copper
      proteins investigated, highlights that the reduction is more marked in the
      azurins compared to amicyanin and that the Cys3Ala/Cys26Ala azurin mutant has a
      structural heterogeneity lower than that shown by the wild-type protein. The
      remarkable similarity of the copper coordination sphere of the proteins suggests
      a more rigid structure of the azurin protein matrix in the absence of the
      disulfide bridge compared to wild-type azurin and of amicyanin with respect to
      both forms of azurin. The former result establishes an important role for the -SS
      bond in modulating the flexibility of wild-type azurin.

PMID- 11508837
TI  - Conformational properties of DNA fragments containing GAC trinucleotide repeats
      associated with skeletal displasias.
AB  - The human gene for cartilage oligomeric matrix protein contains five tandem
      repeats of the GAC trinucleotide. Its expansion by one repeat causes multiple
      epiphyseal dysplasia, while expansion by two repeats or, remarkably, deletion of
      one repeat causes pseudoachondroplasia. Here we used CD spectroscopy, PAGE and UV
      absorption spectroscopy to compare conformational properties of the DNA strands
      containing four, five, six and seven repeats of the GAC trinucleotide. The (GAC)n
      strands were found to form four distinct ordered conformations, depending on the
      solution conditions. The first was a foldback, stable at slightly alkaline pH
      values and low and medium ionic strengths. Increasing salt concentration induced
      a transition of the foldback into an antiparallel right-handed homoduplex. Both
      the conformers contained the Watson-Crick G.C pairs while the intervening
      adenines contributed little to their B-like conformation. Thirdly, the strands
      associated into a parallel homoduplex stabilized by the hemiprotonated C+.C pairs
      and by the GpA steps that both favor the parallel DNA strand orientation. The
      parallel homoduplex was stable even at neutral pH. The fourth conformation was
      the left-handed Z-DNA, which formed easier with (GAC)n than with (GC)n of
      comparable length, indicating that the adenines of (GAC)n promoted the left
      handed duplex. The paper shows that stability of the above four conformers
      strongly depends on the GAC repeat number.

PMID- 11508838
TI  - Ionization properties of titratable groups in ribonuclease T1. I. pKa values in
      the native state determined by two-dimensional heteronuclear NMR spectroscopy.
AB  - pKa values of amino acid side chains of ribonuclease T1 have been determined from
      the pH dependence of 13C and 15N resonances. It was possible to derive pKa values
      of single protonation or deprotonation sites of carboxylate and imidazole groups.
      Deviations from pKa values of free amino acids could be interpreted with
      electrostatic interactions of corresponding side chains with the protein
      environment. In particular, the interaction between H27 and E82 led to an
      increase of the H27 pKa and a decrease of the E82 pKa. The pKa of E28 at the C
      terminal end of the alpha-helix was increased because of the dipolar character of
      the alpha-helix. D76 did not titrate in the investigated pH range of about 2-9.
      From the chemical shift value this buried side chain seems to be protonated. The
      pKa values of side chains in the active site deviate from a normal behaviour. The
      lower pKa value of E58 may be interpreted with the close proximity of this side
      chain with positively charged H40 and R77. A novel two-dimensional
      1H(13Cdelta)13Cgamma correlation experiment was developed to observe the pH
      dependence of the chemical shifts of the Cgamma resonances of histidine residues.
      From the inspection of the Cgamma chemical shift-pH profiles it was possible to
      determine the predominant tautomeric form for the histidine residues at higher pH
      values.

PMID- 11508839
TI  - Ionization properties of titratable groups in ribonuclease T1. II. Electrostatic
      analysis.
AB  - The experimental NMR data for the individual titratable groups in ribonuclease T1
      presented in the preceding paper were analysed by means of a continuum dielectric
      model. The role of two factors, the alteration of hydrogen loci on the ionizable
      groups and the conformational flexibility, were analysed. It was suggested that
      the position of the titratable hydrogen is essential mainly for strongly
      interacting groups. For groups which are accessible to the solvent and whose
      ionization is not coupled with the ionization of neighbouring groups, this factor
      can be neglected. The influence of the conformational flexibility on the
      electrostatic interactions becomes apparent for the environment of K25. For some
      strongly interacting groups, non-sigmoidal ionization curves were calculated. On
      this basis the pH dependence of the NMR chemical shift of the 13Cepsilon2
      resonance of H27, whose ionization is coupled with E82, was reproduced.

PMID- 11508840
TI  - The mechanism of the stabilization of the hexagonal II (HII) phase in
      phosphatidylethanolamine membranes in the presence of low concentrations of
      dimethyl sulfoxide.
AB  - Dimethyl sulfoxide (DMSO), a water-miscible organic solvent, has been used as a
      cryoprotectant for cells. It is known that DMSO stabilizes the HII phase of
      phosphatidylethanolamine (PE) membranes rather than the Lalpha phase, while most
      other water-miscible organic solvents such as acetone and ethanol destabilize the
      HII phase. To elucidate the mechanism for this stabilizing effect of DMSO on the
      HII phase, we have investigated its effects on the structures and physical
      properties of PE membranes. X-ray diffraction data indicated that
      dipalmitoleoylphosphatidylethanolamine (DPOPE) membranes in H2O at 20 degrees C
      were in the Lalpha phase and that an Lalpha to HII phase transition occurred at
      X=0.060 (mole fraction of DMSO) in water/DMSO mixtures. As the DMSO concentration
      increased, the basis vector length of the dioleoylphosphatidylethanolamine
      (DOPE)/ 16 wt% tetradecane membrane and also of the DPOPE/ 16 wt% tetradecane
      membrane in the HII phase decreased, suggesting that the spontaneous curvature of
      these membranes increased. We have also investigated the effects of DMSO on the
      physical properties of the PE membranes, and compared them with those of acetone.
      As the DMSO concentration increased, the excimer to monomer fluorescence
      intensities of pyrene-phosphatidylcholine in the PE membranes decreased,
      indicating that the membrane fluidity decreased, and also the generalized
      polarization value of the Laurdan fluorescent probe in the DPOPE membrane
      increased, indicating that the polarity of the membrane interface decreased. On
      the other hand, acetone had the opposite effects to DMSO. The interaction free
      energy between the membrane surface segments and solvent increased with an
      increase in DMSO concentration. It decreased the amount of solvent in the
      membrane interface, inducing an increase in the spontaneous curvature. This can
      reasonably explain the effects of DMSO on the phase stability and the physical
      properties of the membranes.

PMID- 11508841
TI  - On the Na+,K+ pump in fluctuating membrane potentials.
AB  - The present work investigates the usefulness of noise in the activity of the
      Na+,K+ pump. Random gating activity of the neighboring ion channels causes local
      fluctuations of the electric potential. They are modeled by a Markovian symmetric
      dichotomic noise, added to the membrane potential. The noise-averaged pump
      current is calculated for a general rectangular voltage signal and the model
      parameters of the effective two-state enzyme cycle are tuned to fit experimental
      results. Then, using these parameters, the amount of transported charge is
      calculated, and studied as a function of noise intensity. Signal and noise
      characteristics are identified at which fluctuations enhance pump activity. The
      biological impact of this phenomenon seems to be absent in physiological
      conditions for it occurs at noise amplitudes over 50 mV, which are unlikely to
      appear due to ion channels. However, under some conditions, externally applied
      dichotomic noise of intensity about 150 mV may sensibly increase the quantity of
      transported charge.

PMID- 11508842
TI  - Pink-noise behaviour of biosystems.
AB  - Pink (1/f) noise is one of the most common behaviours of biosystems. Our present
      paper is devoted to clarify the origin of this interesting phenomenon. It is
      shown that the stationary random stochastic processes under self-similar
      conditions (as we have in living objects) generate pink noise independently of
      the kind and number of variables.

PMID- 11508843
TI  - Male reproductive effect of arsenic in mice.
AB  - Arsenic, a known human carcinogen, was given to mice via drinking water as sodium
      arsenite at a dose 53.39, 133.47, 266.95 and 533.90 micromol 1 for 35 days. A
      decrease in the activity of 17 beta HSD along with increase in LDH, gammaGT
      activity were observed at 533.90 micromol l. The observed sperm count, motility
      and morphological abnormalities in sperm were similar to control at lower dose
      levels. However at 533.90 micromol l a significant decrease in sperm count and
      motility along with increase in abnormal sperm were noticed. Significant
      accumulation of arsenic in testes and accessory sex organs may be attributed to
      the arsenic binding to the tissues or greater cellular uptake. No effects were
      observed on indices studied for reproductive effects at 53.39 micromol l arsenic
      close to which human being are exposed through drinking water under the present
      set of experimental conditions.

PMID- 11508844
TI  - Heterobactins: A new class of siderophores from Rhodococcus erythropolis IGTS8
      containing both hydroxamate and catecholate donor groups.
AB  - We report here on a new class of siderophores isolated from Rhodococcus
      erythropolis IGTS8, the first structurally characterized from any species of
      Rhodococcus and for which we suggest the name heterobactins. These siderophores
      consist of a tripeptide of sequence (N-OH)-L-Orn-Gly-D-Orn-(delta-N
      dihydroyxbenzoate). The alpha amino group of the D-Orn is derivatized either as a
      2-hydroxybenzoxazolate in heterobactin A or remains free in heterobactin B. The
      structures were determined by a combination of amino acid analysis, mass
      spectrometry and NMR methods. The two new compounds are true siderophores in that
      they relieve iron limited growth in the producing strain. The heterobactins are
      also transported by other non-producing bacteria. Growth promotion tests using
      various transport mutants revealed that in E. coli heterobactin A is only
      recognized by the catecholate receptor Cir while heterobactin B is taken up in
      both E.coli and A. flavescens JG9 via a hydroxamate transport system.

PMID- 11508845
TI  - The changes in the antioxidant status of heart during experimental hypomagnesemia
      in balb/c mice.
AB  - The present experiment was performed to assess if hypomagnesemia can influence
      antioxidant status in mice heart. The results could explain possibly a free
      radical theory of heart damage in magnesium deficiency. We used a rodent model of
      hypomagnesemia. The magnesium sufficient group received a standard diet whereas a
      magnesium deficient group received the diet containing a trace amount of
      magnesium. The activities of the most important antioxidant enzymes--catalase,
      glutathione peroxidase and superoxide dismutase were assessed in mice heart and
      liver in a time dependent manner, on the 10th and the 20th day of experiment. The
      level of magnesium in plasma of animals receiving the magnesium deficient diet
      dropped twice after the 8th day and four times after the 13th day and then
      reached a plateau value. The activity of catalase in heart in the magnesium
      deficient group increased gradually and was significantly (P < 0.05) elevated by
      27% on the 20th day of experiment whereas the superoxide dismutase activity was
      significantly decreased by 17% on the 20th day. Glutathione peroxidase activity
      was insignificantly elevated. The alterations of antioxidant enzyme activities in
      the heart indicate cardiomyocytes's exposure to oxidative stress, which can be
      responsible for the cardiac lesions observed during hypomagnesemia.

PMID- 11508846
TI  - Cloning and expression of the ferredoxin gene from extremely halophilic archaeon
      Haloarculajaponica strain TR-1.
AB  - The gene encoding a ferredoxin (Fd) from Haloarculajaponica strain TR-1 was
      cloned and sequenced. Sequence analysis of the cloned Ha. japonica Fd gene
      revealed that the structural gene consisted of an open reading frame of 387
      nucleotides encoding 129 amino acids. The deduced amino acid sequence of Ha.
      japonica Fd showed 84 to 98% identity with corresponding sequences in other
      extremely halophilic archaea. The Ha. japonica Fd gene was inserted into the
      shuttle vector pWL102 and used to transform Ha. japonica. Ha. japonica Fd could
      then be produced as a fusion with His-Tag (6xHis) in Ha. japonica host cells. The
      absorption and ESR spectra of the Fd/His Tag fusion protein revealed the presence
      of a [2Fe-2S] cluster which is characteristic of native Ha. japonica Fd.

PMID- 11508847
TI  - Pattern of cadmium accumulation and essential cations during growth of cadmium
      tolerant fungi.
AB  - The present study evaluates the growth response of two strains of filamentous
      fungi; a Fusarium sp. and Alternaria tenuis, grown on both solid and liquid
      Czapek Dox medium amended with different concentrations of CdCl2. Colony
      extension and the mycelial dry weight of both fungi were significantly inhibited
      by high concentrations of cadmium. Extended lag phases and low growth rates
      resulted from cadmium administration. Cadmium drastically affected fungal
      morphogenesis by the production of stunted sterile thick mycelial filaments of
      the Fusarium sp. and chains of uncharacterized swellings instead of conidia in A.
      tenuis. Experiments showed that cadmium accumulation by the Fusarium sp. grown in
      liquid medium was a concentration dependent, and over the incubation time it
      displayed a plateau pattern. The cells grown on medium containing 0.25 mmol l(-1)
      CdCl2 accumulated up to 89 +/- 12 ,umol Cd (gm dw)(-l) after two days, falling to
      approximately 29 +/- 10 mol Cd (gm dw)(-1) after five days. At 0.5 mmol l(-1)
      CdCl2 treatment the maximum cellular cadmium content was approximately 132 +/- 14
      micromol (gm dw)(-1), attained after 3 days, and decreased to degrees 98 +/- 9
      micromol (gm dw)(-1) at the end of the incubation time. There was a simultaneous
      marked drop in cadmium content and pH of the growth medium during the first few
      days. The presence of cadmium markedly altered the cellular essential cations; K+
      and Mg2+ being decreased while Na+ increased during the growth period. Such
      findings resulted a reverse pattern of cellular Na+/K+ ratio for cells grown on
      cadmium-containing medium in respect to the control treatment. The results are
      discussed in relation to a further dimension of cadmium effects that might
      reflect its toxicity, as well as the implication of cadmium extrusion for
      tolerance during fungal growth.

PMID- 11508848
TI  - The remarkable hydrophobic effect of a fatty acid side chain on the microbial
      growth promoting activity of a synthetic siderophore.
AB  - The ability of synthetic derivatives of the siderophore tripeptide of N5-hydroxy
      N5-acetyl-L-ornithine to promote the growth of various strains of mycobacteria
      and Gram negative bacteria was found to depend significantly on the hydrophobic
      nature of the derivative. Although the tripeptide of N5-hydroxy-N5-acetyl-L
      ornithine is not normally utilized by mycobacteria, an N-terminal palmitoyl
      derivative mimicked natural mycobactin J in all studies.

PMID- 11508849
TI  - Structure-activity relationship studies of protective function of nitroxides in
      Fenton system.
AB  - The aim of this study was to evaluate the effect of piperidine nitroxides and
      their amine precursors on deoxyribose oxidation in the Fenton system. Protecting
      activity of nitroxides was found to be concentration-dependent and strongly
      influenced by ring substituents, while secondary amines did not provide any
      protection. The reported results suggest a mechanism of nitroxide action through
      iron oxidation rather than through direct scavenging of hydroxyl radicals.
      Moreover, presented data point to the danger of interference of nitroxides during
      the TBARS assay procedure.

PMID- 11508850
TI  - Interactions of three eco-types of Acidithiobacillus ferrooxidans with U(VI).
AB  - The interaction of uranium with cells of three recently described eco-types of
      Acidithiobacillus ferrooxidans recovered from uranium mining wastes was studied.
      The uranium sorption studies demonstrated that the strains from these types
      possess different capabilities to accumulate and tolerate uranium. The amount of
      uranium biosorbed by all A. ferrooxidans strains increased with considerable
      concentrations. We have found that the representatives of type II accumulate
      significantly higher amounts of uranium in comparison to the other A.
      ferrooxidans strains. The investigations of the tolerance to uranium showed that
      the types I and III are resistant to 8 and 9 mM of uranium respectively, whereas
      the type II does not tolerate more than 2 mM of uranium. The recovery of the
      accumulated uranium by desorption was investigated using various desorbing agents
      as sodium carbonate, sodium citrate and EDTA at different concentrations. Sodium
      carbonate was the most efficient desorbing agent, removing 97% of the uranium
      sorbed from the cells of A. ferrooxidans type III, and 88.33 and 88.50% from the
      cells of the types I and II, respectively.

PMID- 11508851
TI  - Aluminum-induced apoptosis in PC12D cells.
AB  - The addition of aluminum-maltol complex to PC12D cells induced a time-dependent
      and concentration-dependent growth inhibition as well as cell death, whereas
      aluminum chloride or maltol alone did not affect the viability of PC12D cells.
      Apoptosis of differentiated PC12D cells was assessed by using terminal
      deoxynucleotidyltransferase-mediated 2'-deoxyuridine-5'-triphosphate nick end
      labeling (TUNEL) technique to detect DNA strand breaks in situ. The number of
      TUNEL-positive cells treated with aluminum-maltol increased with time in the
      treatment cultures. The ability of aluminum ion to elevate intracellular reactive
      oxygen species was determined by fluorescence in PC12D cells loaded with the
      oxidant-sensitive dye 2',7'-dichlorofluorescin diacetate. Aluminum ion
      incorporated to PC 12D cells causes apoptotic cell death by enhancing the
      generation of reactive oxygen species.

PMID- 11508852
TI  - Old iron, young copper: from Mars to Venus.
AB  - Iron and copper are metals which play an important role in the living world. From
      a brief consideration of their chemistry and biochemistry we conclude that the
      early chemistry of life used water soluble ferrous iron while copper was in the
      water-insoluble Cu(I) state as highly insoluble sulphides. The advent of oxygen
      was a catastrophic event for most living organisms, and can be considered to be
      the first general irreversible pollution of the earth. In contrast to the
      oxidation of iron and its loss of bioavailability as insoluble Fe(III), the
      oxidation of insoluble Cu(I) led to soluble Cu(II). A new iron biochemistry
      became possible after the advent of oxygen, with the development of chelators of
      Fe(III), which rendered iron once again accessible, and with the control of the
      potential toxicity of iron by its storage in a water soluble, non-toxic, bio
      available storage protein (ferritin). Biology also discovered that whereas
      enzymes involved in anaerobic metabolism were designed to operate in the lower
      portion of the redox spectrum, the arrival of dioxygen created the need for a new
      redox active metal which could attain higher redox potentials. Copper, now
      bioavailable, was ideally suited to exploit the oxidizing power of dioxygen. The
      arrival of copper also coincided with the development of multicellular organisms
      which had extracellular cross-linked matrices capable of resisting attack by
      oxygen free radicals. After the initial 'iron age' subsequent evolution moved,
      not towards a 'copper age', but rather to an 'iron-copper' age. In the second
      part of the review, this symbiosis of iron and copper is examined in yeast. We
      then briefly consider iron and copper metabolism in mammals, before looking at
      iron-copper interactions in mammals, particularly man, and conclude with the
      reflection that, as in Greek and Roman mythology, a better understanding of the
      potentially positive interactions between Mars (iron) and Venus (copper) can only
      be to the advantage of our species.

PMID- 11508853
TI  - Interleukin-2 and cancer--physiological and pharmacological uses.

PMID- 11508854
TI  - D-fructose-binding proteins in bull seminal plasma: isolation and
      characterization.
AB  - The heparin-binding activity of bull seminal plasma proteins was inhibited by D
      fructose, D-glucose, inulin and glycogen; D-galactose, dextran and mannan had no
      effect. While the ejaculated sperm-heparin interaction was not influenced by the
      presence of saccharides, the heparin-binding activity of epididymal sperm was
      inhibited by D-fructose. The results of the binding studies were confirmed by
      affinity chromatography on immobilized heparin followed by elution with
      monosaccharides. Proteins adsorbed to a heparin-polyacrylamide column and eluted
      with D-fructose were analyzed by RP HPLC, SDS electrophoresis and by
      determination of the N-terminal amino-acid sequence. RNAase dimer, PDC-109 and
      metalloproteinase inhibitor (TIMP-2) were identified.

PMID- 11508855
TI  - Expression of BRCA1, NBR1 and NBR2 genes in human breast cancer cells.
AB  - BRCA1 is a tumour suppressor gene with a caretaker function in the DNA-damage
      repair and the maintenance of genome integrity. The human BRCA1 and NBR2 genes
      and the homologous Brcal and Nbr1 mouse genes are situated head-to-head on human
      chromosome 17q21 and on mouse chromosome 11, respectively. Their transcription
      start sites, located on opposite DNA strands, are separated by 218 bp in humans,
      and by 289 bp in mice. Because of this intimate contact and because of our
      previous observation of a quasi-reciprocal expression pattern of Brca1 and Nbr1
      in mouse spermatogenesis, we estimated here the relative mRNA expression of
      BRCA1, NBR1 (next-to-BRCA1) and NBR2 genes in a panel of permanent cell lines and
      primary cell cultures derived from human breast cancer or normal mammary tissue.
      The analysis revealed highly significant downregulation of BRCA1 in 11 out of 12
      examined tumour cell lines and primary cell cultures as compared to non-malignant
      mammary cells. Two isoforms of NBR1(1A) and the classical NBR1(1B) transcripts
      were found in cells from malignant mammary tissues, all of them downregulated in
      respect to normal cells. The expression of NBR2 differed, being increased in
      three permanent tumour cell lines and slightly decreased in all primary breast
      cancer cell cultures. The in silico analysis revealed two new putative domains of
      the predicted NBR1 protein, suggesting its role in the ubiquitin pathway. The
      recent identification of the ubiquitin protein ligase activity of BRCA1 implies a
      possible functional connection between both genes.

PMID- 11508856
TI  - Y chromosome and vimentin used to trace the fate of allogeneic keratinocytes
      delivered to the wound by the recombined human/pig skin.
AB  - RHPS, composed of confluent allogeneic keratinocytes cultured on cell-free pig
      dermis, stimulates wound healing when applied with the keratinocyte layer facing
      the wound. So far it has not been clarified whether the confluent keratinocytes
      implanted 'upside-down' can 'take' or only stimulate healing by producing growth
      factors. Confluent male keratinocytes were grafted onto donor sites of three
      female patients. Biopsies were taken on days 4, 6 and 9 after grafting. The fate
      of donor cells was followed in paraffin sections by FISH for the Y chromosome and
      by persisting expression of vimentin taken as a marker of cultured keratinocytes.
      Histological evaluation was complemented by detection of keratin 10 and
      involucrin. All three donor sites healed within one week. On day 4 the early
      neoepidermis was multilayered but disordered after transplantation. A large
      proportion of cells were apparently of donor origin as indicated by the presence
      of Y chromosomes, irregular morphology, expression of vimentin in the bottom and
      upper layers of the neoepidermis, and by irregular expression of involucrin and
      keratin 10 only in the central layer of the neoepidermis. From day 6 onwards, the
      new epidermis acquired an ordered stratification. Involucrin and keratin 10
      renewed normal distribution in suprabasal layers. Concomitantly, vimentin
      expression was decreasing. The Y chromosome was still found on day 6 but not on
      day 9. We concluded that confluent allogeneic keratinocytes temporarily 'take' to
      the wound and contribute to rapid wound closure, being replaced by the patient's
      epidermal cells after about one week.

PMID- 11508857
TI  - Necrobiotic process causing burn wound conversion may be prevented by allogeneic
      keratinocytes delivered by the recombined human/pig skin.
AB  - The spontaneous necrobiotic process frequently causes conversion of DDB (deep 2nd
      degree wounds) into full-thickness skin loss (3rd degree wounds). We found that
      this process may be positively influenced by the activity of living human
      allogeneic keratinocytes cultured on acellular pig dermis. This RHPS, if applied
      'upside-down' with the epidermal layer facing the wound, provides an opportunity
      for keratinocytes to influence the healing. The aim of the present study was to
      find conditions, in terms of timing and wound-bed preparation, for optimum
      healing activity of RHPS. The wound beds were prepared either with tangential
      excision, surface dermabrasion or deep dermabrasion. Out of 17 wounds grafted
      with RHPS after tangential excision, 15 (88%) healed in 4-10 days; early excised
      wounds (up to day 5) healed within less than 10 days after the injury. Out of 8
      wounds grafted after surface dermabrasion, only 2 (25%) healed. Out of 6 wounds
      grafted with RHPS after deep dermabrasion, 4 (67%) healed. The optimum healing
      effect of RHPS and prevention of conversion was achieved in early tangentially
      excised wounds.

PMID- 11508858
TI  - Changes in microtubules and microfilaments due to a combined effect of ultrasound
      and cytostatics in HeLa cells.
AB  - Treatment of HeLa cells with low intensity ultrasound and two cytostatic drugs,
      cycloplatin and methotrexate, resulted in a partial disassembly of microtubules
      and microfilaments. This disassembly was due to depolymerization and subsequent
      erroneous repolymeration of essential cytoskeletal proteins, resulting in
      formation of unusual arrangements, mainly small, granule-like structures. The
      combined action of ultrasound and cytostatics had a synergistic effect dependent
      on both the concentration of the drug and the time of sonication. The
      demonstrated changes in the cytoskeleton are considered to be non-specific to
      ultrasound treatment, reflecting only an altered vital state of the treated
      cells.

PMID- 11508860
TI  - Overexpression of the high-affinity Fcgamma receptor (CD64) is associated with
      leukocyte dysfunction in sepsis.
AB  - The morbidity and mortality from sepsis and multiple organ dysfunction syndrome
      (MODS) continues to be high. An increase in FcgammaRI+ (CD64+) monocytes was
      demonstrated in septic patients, and an association between cell number, their
      secretory activity, and poor outcome has been described. In the present
      investigation further characterization of CD64+ leukocytes has been attempted.
      The study was aimed at examining the phagocytic activity (PA) and reactive oxygen
      species (ROS) production by monocytes (Mo) and neutrophils (Neu) in sepsis and
      sepsis-induced acute respiratory distress syndrome (ARDS) related to the pattern
      of CD64 expression. Twenty-three post-traumatic or post-operative male and female
      patients with sepsis were enrolled. The control group consisted of 10 healthy
      volunteers. Arterial blood samples were taken during the septic episode for flow
      cytometric analysis of surface leukocyte antigens, phagocytosis, and ROS
      production. CD64 expression on Mo and Neu was markedly increased in septic
      patients (P = 0.029 and P = 0.0005), and even more in sepsis with ARDS (P =
      0.011). In healthy individuals, PA of CD64+ Neu was higher, than of CD64- cells
      (P = 0.021). In septic patients, decreased PA was detected in CD64+ Mo and Neu (P
      = 0.013 and P = 0.040, respectively). CD64+ Neu of patients in ARDS exhibited the
      most prominent PA depression (P = 0.048). ROS production in non-separated Mo and
      Neu was increased in sepsis (P = 0.026 and P = 0.004, respectively). In healthy
      individuals CD64+ Neu and stimulated CD64+ Mo demonstrated increased ROS
      synthesis compared to matched CD64- cells (P = 0.001 and P = 0.042,
      respectively). Although ROS production by CD64+ leukocytes in sepsis was also
      increased compared to CD64- cells, significantly less ROS was generated compared
      to healthy subjects (P = 0.021). In conclusion, overexpression of CD64 on blood
      Mo and Neu from patients with sepsis and ARDS is associated with depressed PA and
      decreased oxidative response.

PMID- 11508859
TI  - New monoclonal antibodies recognizing p53 protein phosphorylated by casein kinase
      II at serine 392.

PMID- 11508861
TI  - Procalcitonin and CGRP-1 mrna expression in various human tissues.
AB  - Procalcitonin (PCT) is a highly sensitive and specific marker of systemic
      bacterial infection and sepsis. In contrast to its diagnostic significance, the
      cellular sources of plasma procalcitonin remain to be clarified. Two forms of PCT
      mRNAs originate from calcitonin/calcitonin gene-related peptide gene (CALC-I
      gene) along with mRNA for calcitonin gene-related peptide-I (CGRP-I). Reverse
      transcription polymerase chain reaction with newly designed primers detecting
      different PCT mRNAs and CGRP-I mRNA was used to identify tissues that might
      contribute to PCT production. Our study indicates that a variety of human tissues
      (13 of the 16 analyzed overall) express PCT-I, PCT-II, and/or CGRP-I mRNAs, with
      the highest levels detected for liver, testis, lung, prostate, kidney, and small
      intestine. Various tissues differ in the proportions of PCT-I, PCT-II, and CGRP-I
      mRNA expression levels. Thus we demonstrate the complexity of tissue-specific
      regulation of CALC-I gene expression and suppose a variety of tissues as a
      potential source of CALC-I-encoded peptides.

PMID- 11508862
TI  - Arginase release from red blood cells: possible link in transfusion induced
      immune suppression?
AB  - Arginine stimulates lymphocyte function and is degraded by arginase, an enzyme
      that is abundantly present in red blood cells. Arginase impairs lymphocyte
      function and responses in vitro. Leakage of arginase from stored red blood cells
      may be involved in the lymphocyte dysfunction associated in allogenic blood
      transfusion. In the present study, arginase activity was determined in bags of
      red cells stored for transfusion. Buffy coat depleted red blood cells were
      obtained routinely from four healthy donors and stored in bags for a maximum
      period of five weeks at 4 degrees C. The bags were sampled for determination of
      arginase, lactate dehydrogenase, and potassium. In addition, a random sample of
      36 bags of red blood cells about to be transfused to patients were studied.
      Levels of arginase, lactate dehydrogenase, and potassium showed a time dependent
      increase in the bags of the four donors. This time dependent increase in arginase
      activity could be confirmed in the additional bags sampled (P < 0.0001, r =
      0.78). The results for the first time show that arginase is released from red
      blood cells during storage for transfusion. Arginase infusion may play an
      important role in the immune suppression observed after blood transfusion.

PMID- 11508863
TI  - Glycine reduces the inflammatory response and organ damage in a two-hit sepsis
      model in rats.
AB  - The goal of this study was to investigate whether prefeeding of glycine reduces
      the immunoinflammatory response, the degree of distant organ injury (liver),
      and/or the mortality rate in a two-hit model using intestinal
      ischemia/reperfusion and endotoxin (ET) challenge 6 h later in rats. The liver
      damage was greatest at 24 h after ET challenge and completely inhibited by
      glycine. The early systemic increase of the proinflammatory cytokines tumor
      necrosis factor-alpha (TNF-alpha) and interleukin (IL) -6 as well as the
      secretion of the antiinflammatory cytokine IL-10 was reduced by glycine. Tissue
      cytokine mRNA expression (TNF-alpha, IL-1beta, IL-10) was decreased in the lung
      and the liver but not in the mesenteric lymph node or ileum, in the glycine-fed
      group. However, glycine did not decrease the mortality rate. These results
      suggest that prefeeding of glycine reduces liver damage as well as the systemic
      and local (lung and liver) inflammatory response after intestinal
      ischemia/reperfusion and endotoxin challenge in rats.

PMID- 11508864
TI  - Development of an acute burn model in adult mice for studies of cardiac function
      and cardiomyocyte cellular function.
AB  - The increasing availability of mice with gene supplementation (transgenic), site
      specific inactivation mutations (gene "knock-outs"), or site-specific genetic
      modification mutations (gene "knock-ins") has spurred interest in the development
      of murine trauma models. In this study, C57 BL/6 mice (28 g) were given a
      cutaneous burn over 40% total body surface area by applying brass probes (1 x 2 x
      0.003 cm) heated to 100 degrees C in boiling water to the animals side and back
      for 5 s. Shams received anesthesia alone and not burn. Mice were killed 24 h post
      burn to determine presence of partial-thickness or full-thickness burn injury,
      cardiac contractile function (Langendorff perfusion, n = 7 or 8 mice/group) or to
      examine cardiac myocyte cytokine secretion in isolated cardiomyocytes
      (collagenase perfusion, n = 4 or 5 mice/group). All mice were killed 24 h post
      burn for subsequent cardiac or cardiomyocyte studies. Our studies confirm that
      this murine model of burn trauma produced mixed partial- or full-thickness burn
      injury, whereas there was no necrosis or inflammation in sham burn mice. Baseline
      hematocrits were similar in all mice (44+/-1) but decreased after burn trauma
      (37+/-1), likely because of the volume of fluid resuscitation and hemodilution.
      Burn trauma impaired cardiac contraction and relaxation as indicated by the lower
      left ventricular pressure (LVP) measured in burn (56+/-4) compared to that
      measured in shams (84+/-1 mmHg, P < 0.001), a lower rate of LVP rise (+dP/dt max,
      1393+/-10 vs. 2000+/-41 mmHg/s, P < 0.002), and reduced LVP fall (-dP/dt max,
      1023 - 40 vs. 1550+/-50, P < 0.001). These differences occurred despite similar
      coronary perfusion pressures and heart rates in both sham and burn mice.
      Ventricular function curves were shifted downward in the burn mice in the
      direction of contractile failure; in addition, hearts from burn mice had reduced
      LVP and +dP/dt responses to increases in coronary flow rate, increases in
      perfusate Ca2+, and to isoproterenol challenge (P < 0.05). Burn trauma promoted
      cardiac myocyte secretion of tumor necrosis factor (TNFalpha) (175+/-6 pg/mL)
      compared to that measured in shams (72+/-9 pg/mL, P < 0.05); burn trauma also
      increased cardiac myocyte secretion of interleukin 1beta (IL-1beta) (sham: 2+/
      0.5; burn: 22+/-1 pg/mL, P < 0.05) and IL-6 (sham: 70+/-6; burn: 148+/-16 pg/mL,
      P < 0.05). Anti-TNFalpha strategies prevented burn-mediated cardiac contractile
      deficits. Burn trauma altered Ca2+ homeostasis in murine cardiomyocytes (Fura-2
      AM loading). [Ca2+]i in myocytes from burns (185+/-4 nM) was higher than values
      measured in myocytes from shams (86+/-nM, P < 0.05). These data confirm that the
      murine burn model provides a reasonable approach to study the molecular and cell
      biology of inflammation in organ dysfunction after burn trauma.

PMID- 11508865
TI  - Effects of combined selective iNOS inhibition and peroxynitrite blockade during
      endotoxemia in pigs.
AB  - We investigated the effect of mercaptoethylguanidine (MEG, 3 mg kg(-1)h(-1)), a
      combined selective inducible nitric oxide synthase (iNOS) inhibitor, a
      peroxynitrite and oxygen free radical scavenger with cyclooxygenase-inhibitor
      properties on intestinal and hepatic perfusion, O2 exchange, and metabolism
      during long-term hyperdynamic porcine endotoxemia. MEG was started 12 h after
      onset of endotoxemia. At baseline and after 12, 18, and 24 h of endotoxemia,
      hepatic arterial and portal venous blood flow, ileal mucosal-arterial PCO2 gap,
      portal and hepatic venous lactate/pyruvate ratio, free glutathione (GSH), and 8
      isoprostanes were measured. Expired NO and plasma nitrate levels were assessed as
      well. MEG blunted the endotoxin-induced increase in expired NO and prevented the
      progressive fall in blood pressure without affecting cardiac output. It
      attenuated both systemic and regional venous acidosis without influencing the
      impairment of hepatosplanchnic metabolism nor counteracting the increase in GSH
      levels. In our model MEG failed to beneficially affect variables of oxidative
      stress.

PMID- 11508866
TI  - Does the activation of poly (ADP-ribose) synthetase mediate tissue injury in the
      sepsis induced by cecal ligation and puncture?
AB  - Poly (ADP-ribose) synthetase (PARS) is a DNA protective enzyme activated by
      single-strand breakage. It is suspected that exaggerated PARS activation related
      to biochemical stress by reactive oxygen and nitrogen species contributes to
      cellular injury in sepsis. The main hypothesis is that PARS activation leads to
      massive ATP and NAD consumption and consequent cellular energy depletion. The
      PARS inhibitor 3-amino-benzamide (3AB) is protective in rodents challenged with
      either endotoxin or intraperitoneal zymozan. The present experiment was designed
      to test the effect of 3AB in a more clinically relevant model of sepsis, namely
      polymicrobial sepsis induced by cecal ligature and puncture (CLP). Adult male
      Wistar rats were anesthetized, instrumented with catheters in the jugular vein
      and in the carotid artery, and then randomized into three groups: Sham (no
      laparotomy, n = 13), CLP (n = 15), and CLP/3AB (n = 18). All animals were allowed
      to recover and they received a continuous intravenous infusion of saline (20
      mL/kg/h) and fentanyl (20 microg/kg/h). 3AB was administered to the CLP/3AB group
      as an intravenous bolus (10 mg/kg) followed by a continuous intravenous infusion
      (10 mg/kg/h). After 24 h, blood was drawn for the determination of biological
      indicators of organ injury. Rats were then anesthetized and biopsies of the liver
      were quickly frozen into liquid nitrogen for the subsequent determination of NAD
      and ATP levels. Further organ samples were collected for the assay of
      myeloperoxidase (MPO) to indicate tissue infiltration by leukocytes, and
      nitrotyrosine to indicate the level of biochemical stress by reactive nitrogen
      species. Twenty-four-hour mortality was 0/13 (Sham), 1/15 (CLP), and 5/18
      (CLP/3AB; p = NS). In the surviving rats, CLP induced a clear elevation of liver
      enzymes, bilirubin, and pancreatic lipase, but not creatinine in the plasma, as
      well as a marked increase of MPO activity in liver, jejunum, and lung, but not
      kidney or heart. None of these variables was affected by treatment with 3AB.
      Furthermore, CLP did not cause depletion of NAD or ATP in the liver, nor any
      change in the nitrotyrosine content of any organ. These data argue against a
      general role of PARS activation in the pathogenesis of sepsis-induced tissue
      injury.

PMID- 11508867
TI  - Ex vivo fluorescence microscopy provides simple and accurate assessment of
      neutrophil-endothelial adhesion in the rat lung.
AB  - Neutrophil adhesion to the pulmonary endothelium is prerequisite to neutrophil
      transmigration and activation, both of which may lead to lung injury. A simple
      method to evaluate neutrophil adherence in the lung would be useful for
      developing new strategies for neutrophil-mediated lung injury. The purpose was to
      establish a simple method to evaluate neutrophil adhesion in the lung using ex
      vivo fluorescence microscopy. Rats were anesthetized, and the right jugular veins
      were catheterized. Neutrophils were isolated from another set of rats and labeled
      with 5,(6)-carboxyfluorescein diacetate. Animals were killed 120 s after a 1 x
      10(6) labeled neutrophil injection. The pulmonary labeled neutrophil number was
      counted under a fluorescence microscope. In the first experiment, rats were given
      0, 20, 200, or 2000 microg/kg lipopolysaccharide (LPS) i.p. At 4 h after
      challenge, the pulmonary labeled neutrophil number was determined. Kinetic
      studies were also performed at 0, 1, 4, and 8 h after 200 microg/kg LPS. Finally,
      anti-ICAM-1 Ab was injected i.v. before LPS 200 microg/kg, and the labeled
      neutrophil number in the lung was determined at 4 h. The number of pulmonary
      labeled neutrophils was higher after LPS 200 or 2000 microg/kg than after the
      other doses. The pulmonary labeled neutrophil number was increased at 4 h
      compared with the other time points. ICAM-1 blocking normalized the pulmonary
      labeled neutrophil number in the LPS group. In conclusion, our method seems to
      reflect ICAM-1-mediated neutrophil adherence to the endothelium in the present
      setting. This simple technique may be useful for evaluating neutrophil adhesion.

PMID- 11508869
TI  - The protective effect of hypervolemic hemodilution in experimental heatstroke.
AB  - The authors tested the hypothesis in a rat model that hypervolemic hemodilution
      during heatstroke affected the mean arterial pressure (MAP), striatal dopamine
      (DA) release, and local cerebral blood flow and neuronal damage score in
      different brain structures. The heatstroke was induced by exposing the urethane
      anesthetized rats to an ambient temperature of 42 degrees C. Hypervolemic
      hemodilution was produced by intravenous administration of 10% human albumin.
      Relative and absolute blood flow in the corpus striatum were determined using the
      laser Doppler flowmetry and the autoradiography diffusible tracer technique,
      respectively. The DA release in the striatum was estimated using the in vivo
      microdialysis technique. After onset of heatstroke, animals with hypervolemic
      state alone, produced by saline or heparinized blood injection, displayed higher
      values of DA release, as well as neuronal damage score in the striatum,
      hypothalamus, or cortex, but lower values of MAP and blood flow in the striatum,
      hypothalamus, or cortex compared to normothermic controls. However, the
      heatstroke-induced arterial hypotension, cerebral ischemia, increased striatal DA
      overload, and increased neuronal damage score were attenuated by induction of
      both hypervolemic and hemodilution state with 10% albumin either before or after
      the onset of heatstroke. In addition, constant infusions of a vasopressor agent
      phenylephrine (2 microg kg(-1) min(-1)) after the onset of heatstroke failed to
      maintain appropriate levels of MAP and resulted in no protection against
      heatstroke. Thus, it appears that the observed benefit of the 10% albumin is
      secondary to hemodilution and/or maintenance of MAP.

PMID- 11508868
TI  - Comparison of translocation of different types of microorganisms from the
      intestinal tract of burned mice.
AB  - The aim of this study was to compare the ability of various microorganisms to
      translocate from the intestine to the mesenteric lymph nodes (MLNs), liver, and
      spleen in a burned mouse model. Balb/c mice were gavaged with 1 x 10(9) or 1 x
      10(10) of one of 11 different microorganisms. All animals were then given a 20%
      burn. Survival after 10 days showed no significant difference between any of the
      groups at the 10(10) dose. At the 10(9) dose, significantly higher survival rates
      were found in three of the 11 strains. Microbial translocation (gavage of 10(10)
      111In-labeled organisms) and host's ability to kill translocated bacteria (viable
      bacteria in tissues) were measured followed by burn injury and sacrifice four
      hours later. Translocation and killing of Staphylococcus epidermidis and
      Escherichia coli was high in the MLNs compared with all other groups but
      translocation was lower to the liver. Klebsiella, Pseudomonas, and Serratia
      translocated more evenly to all the tissues. However, these groups showed very
      high clearance of bacteria in the liver and spleen except for Klebsiella and one
      strain of Pseudomonas in the spleen. Candida showed poor translocation to all of
      the tissues and high clearance. It is concluded that various strains of bacteria
      translocate from the intestine to a similar degree after injury, but the tissues
      to which they translocate and the rate at which they are killed are somewhat
      strain dependent.

PMID- 11508870
TI  - Poly(adp-ribose) synthetase inhibition reduces bacterial translocation in rats
      after endotoxin challenge.
AB  - We investigated whether 3-aminobenzamide (3-AB), a poly(ADP-ribose) synthetase
      (PARS) inhibitor, reduces bacterial translocation (BT) after intraperitoneal
      endotoxin administration. Wistar rats were randomized to receive intraperitoneal
      saline (control, n = 6); endotoxin (n = 8); 3-AB (n = 6); and 3-AB plus endotoxin
      (n = 8). Six hours later, to evaluate the endotoxin-related intestinal injury and
      BT, tissue and blood samples were collected. Administration of intraperitoneal
      endotoxin caused severe intestinal injury and BT to mesenteric lymph nodes. PARS
      inhibition with 3-AB completely prevented endotoxin-induced BT. No colony-forming
      bacteria was isolated from the samples obtained from 3-AB-pretreated animals
      under endotoxin challenge. Treatment with 3-AB significantly reduced the
      endotoxin-induced intestinal mucosal injury. The inhibition of PARS by its
      blocker 3-aminobenzamide during endotoxemia prevents bacterial translocation and
      intestinal injury in rats. PARS activation may provide a novel therapeutic
      approach in reducing gut barrier failure seen in endotoxemia.

PMID- 11508871
TI  - Sepsis syndromes: understanding the role of innate and acquired immunity.
AB  - An intact innate and acquired immune response are essential for defeating
      systemic microbial infections. Recognition molecules, inflammatory cells, and the
      cytokines they produce are the principal means for host tissues to recognize
      invading microbes and to initiate intercellular communication between the innate
      and acquired immune systems. However, activation of host innate immunity may also
      occur in the absence of microbial recognition, through expression of internal
      "danger" signals produced by tissue ischemia and necrosis. When activation of the
      innate immune system is severe enough, the host response itself can propel the
      patient into a systemic inflammatory response syndrome (SIRS), or even multiple
      system organ failure (MSOF) and shock. Although most patients survive the initial
      SIRS insult, these patients remain at increased risk of developing secondary or
      opportunistic infections because of the frequent onset of a compensatory anti
      inflammatory response syndrome (CARS). The initial activation of the innate
      immune response often leads to macrophage deactivation, T-cell anergy, and the
      rapid apoptotic loss of lymphoid tissues, which all contribute to the development
      of this CARS syndrome and its associated morbidity and mortality. Initial efforts
      to treat the septic patient with anticytokine therapies directed at the SIRS
      response have been disappointing, and therapeutic efforts to modify the immune
      response during sepsis syndromes will require a more thorough understanding of
      the innate and acquired immune responses and the increased apoptosis in the
      lymphoid tissue.

PMID- 11508872
TI  - Elevated serum levels of S-100B reflect the extent of brain injury in alcohol
      intoxicated patients after mild head trauma.
AB  - Elevated systemic levels of S-100B are proposed as a potential indicator of brain
      damage in identifying high-risk patients after mild head trauma (MHT). Although
      incidence of alcohol intoxication is high in these patients, the influence of
      alcohol intoxication on S-100B levels is unclear. Therefore, the aim of our study
      was to investigate serum concentrations of S-100B in intoxicated (group 1) and
      sober (group 2) patients after MHT in comparison with those of mild (group 3) or
      severely intoxicated (group 4) individuals without trauma. S-100B was
      significantly increased in MHT patients exhibiting posttraumatic lesions in
      initial cranial computed tomography scan. Alcohol intoxication did not elevate S
      100B levels in group 3 or 4 subjects. Our data indicate for the first time that
      alcohol intoxication does not influence the diagnostic value of S-100B
      measurements in patients after MHT.

PMID- 11508873
TI  - Macular translocation with 360-degree peripheral retinectomy impact of technique
      and surgical experience on visual outcomes.
AB  - PURPOSE: To evaluate the impact of technique and surgical experience on
      complications and outcomes of macular translocation surgery with 360-degree
      peripheral retinectomy (MTS360). METHODS: Twenty-six consecutive patients
      underwent MTS360 in a prospective study of macular translocation surgery for
      subfoveal choroidal neovascularization (CNV) in eyes with age-related macular
      degeneration (ARMD). Data gathered included intraoperative and postoperative
      events and pre- and postoperative standardized visual acuity recorded as number
      of letters read. Because the surgical technique changed particularly during the
      first 16 cases, patients were grouped into an evolving treatment group of the
      first 16 patients (Group 1) and a modified treatment group of the final 10
      patients (Group 2). RESULTS: As techniques evolved in this series, ease of
      surgery increased. There were significant decreases in surgery duration and in
      number of retinotomies required to induce artificial retinal detachment. Number
      of postoperative retinal detachments decreased from five in Group 1 to none in
      Group 2. Change in visual acuity was significantly different between the two
      groups: Group 1 had an average loss of 14 letters (<3 lines) and Group 2 an
      average gain of 3 letters (<1 line) (P < 0.05). Average postoperative visual
      acuity was significantly better for Group 2 (68 letters, approximately 20/80)
      than for Group 1 (47 letters, approximately 20/250) (P < 0.01). CONCLUSION:
      Surgical experience and a progressively modified surgical technique decreased
      perioperative complications and improved visual outcomes after MTS360. With
      modified MTS360, central vision has been salvaged for almost 1 year of follow-up
      in patients presenting with vision loss from subfoveal CNV and ARMD.

PMID- 11508874
TI  - Successful macular translocation with temporary scleral infolding using
      absorbable sture.
AB  - PURPOSE: To describe successful macular translocation with temporary scleral
      infolding in a series of patients with small subfoveal choroidal
      neovascularization due to age-related macular degeneration or ocular
      histoplasmosis syndrome. METHODS: Ten eyes of 10 consecutive patients were
      studied in a prospective, nonrandomized clinical trial. Macular translocation
      with scleral infolding (MTSI) was performed. Absorbable polyglactin suture was
      used to create temporary scleral infolding. Distance and stability of retinal
      translocation, corneal topography, visual acuity, and rates of complications were
      measured. RESULTS: The median distance of translocation in the early
      postoperative period was 1,700 microm (range, 680-3,200) and did not regress
      after resolution of the scleral infolding. Induced postoperative oblique corneal
      astigmatism resolved, coinciding with the disappearance of peripheral retinal
      elevation due to scleral infolding. Three patients gained more than two lines of
      vision, two patients were within two lines of preoperative vision, and five
      patients lost more than two lines of vision. Complications were similar to
      previously published reports. CONCLUSION: Temporary scleral infolding is an
      effective technique in MTSI. The distance of translocation is comparable to that
      achieved with nonabsorbable suture or scleral resection, and does not regress
      after resolution of the scleral infolding. Induced postoperative corneal
      astigmatism appears to resolve.

PMID- 11508875
TI  - The effect of pars plana vitrectomy in the management of Fuchs heterochromic
      cyclitis.
AB  - PURPOSE: Fuchs heterochromic cyclitis (FHC) is characterized by a unilateral
      chronic iridocyclitis of insidious onset and uncertain cause. Our aim was to
      evaluate the effect of vitreous surgery in patients with FHC and clinically
      significant visual symptoms caused by inflammatory vitreous debris. METHODS: This
      study was a review of 12 eyes of 12 consecutive patients with FHC who underwent
      pars plana vitrectomy for visually significant vitreous opacities. Cataract
      extraction with posterior chamber lens implantation had been performed on four
      eyes preoperatively. Four eyes had a concomitant lensectomy for cataracts, and
      one had a surgical posterior capsulotomy. Visual and anatomic data were recorded
      before surgery and for at least 6 months after surgery. RESULTS: Visual acuity
      improved in all patients from an average logMAR of 0.57 to 0.007 (P = 0.0004) and
      by more than 2 Snellen lines in 8 of 12 of the eyes (P < 0.05). Symptoms of
      floaters resolved in all 11 patients in whom they were a symptom. Vitreous haze
      was cleared completely from an average Nussenblatt grade of 1.7 to 0 after 1 week
      (P = 0.0001). CONCLUSIONS: Pars plana vitrectomy is a safe and effective
      treatment for the visual symptoms associated with FHC and can be combined safely
      with a lensectomy if required.

PMID- 11508876
TI  - Surgical removal of subfoveal choroidal neovascularization without removal of
      posterior hyaloid: a consecutive series in younger patients.
AB  - PURPOSE: Subfoveal choroidal neovascularization (CNV) remains a common and
      important cause of visual loss. Previous studies have suggested that submacular
      surgery may improve or maintain visual acuity, particularly in younger patients.
      The majority of reported cases included removal of the posterior hyaloid during
      vitrectomy. The authors present a consecutive series of patients age 55 or
      younger with subfoveal CNV removal without posterior hyaloid removal. METHODS:
      Seventeen patients without age-related macular degeneration (ARMD), with
      subfoveal CNV from choroiditis, presumed ocular histoplasmosis syndrome, myopia,
      or idiopathic causes, underwent a small retinotomy technique to extract the
      membranes after vitrectomy without posterior hyaloid removal. RESULTS: Median
      improvement in visual acuity was from 20/320 to 20/50. Eleven patients (65%)
      experienced an improvement of three or more lines of Snellen acuity (average
      7.5), 4 (23%) were within two lines of preoperative acuity, and 2 (12%) had
      decreased acuity, with an average follow-up of 12 months (range 3-31). Choroidal
      neovascularization recurred in six patients (35%). Postoperative retinal
      detachment, epiretinal proliferation, or macular hole did not occur. CONCLUSIONS:
      In this series of younger patients with subfoveal CNV not from ARMD, visual
      acuity was improved in the majority after submacular membrane removal. Omission
      of removal of the posterior hyaloid did not adversely affect outcome.

PMID- 11508878
TI  - The role of vitreoretinal surgery in the management of myopic macular hole
      without retinal detachment.
AB  - PURPOSE: To evaluate the anatomic and functional outcome of vitreoretinal surgery
      in eyes with pathologic myopia and macular hole and to determine if surgery
      improves visual acuity. METHODS: Twenty-four consecutive highly myopic eyes with
      full-thickness macular hole without posterior retinal detachment were treated by
      vitrectomy. Posterior hyaloid dissection, removal of epiretinal and internal
      limiting membranes (ILM) if thickened, instillation of platelet concentrate, and
      flushing with 25% sulfur hexafluoride were performed. RESULTS: Patients'
      refractive error ranged between -8.0 and -17.5 diopters, and axial length ranged
      from 27.1 to 31.4 mm. Two epimacular membranes and 10 macular ILM were removed.
      Ten patients also underwent phacoemulsification and intraocular lens implantation
      at the same procedure. Mean preoperative best-corrected visual acuity was 20/200.
      Successful anatomic macular hole closure occurred 6 months postoperatively in
      100% of eyes after one (21 eyes, 87.5%) or two surgeries (3 eyes, 12.5%). Visual
      acuity improved three or more lines in 83.3% of patients. Mean postoperative
      visual acuity was 20/70. No retinal detachment was observed during the follow-up
      period, which ranged from 12 to 45 months. CONCLUSION: Our results suggest that
      vitreoretinal surgery may effectively manage myopic macular holes, thus improving
      anatomic and visual outcomes. By closing the hole, vitreoretinal surgery may
      decrease the risk of posterior retinal detachment in highly myopic eyes.

PMID- 11508877
TI  - Dispase facilitates posterior vitreous detachment during vitrectomy in young
      pigs.
AB  - PURPOSE: To evaluate the role of intravitreal dispase in conjunction with pars
      plana vitrectomy to facilitate the creation of a posterior vitreous detachment
      (PVD) in young pig eyes. METHODS: Twenty-four eyes of 24 animals were randomized
      to receive an intravitreal injection of dispase (50 microg/0.05 mL) or phosphate
      buffered saline (PBS) immediately after core vitrectomy and before attempted
      creation of a posterior cortical vitreous detachment. Following a 15-minute
      waiting period, surgical creation of a posterior vitreous separation was
      attempted by aspiration of the posterior vitreous immediately adjacent to the
      optic disk. Eyes were evaluated postoperatively by clinical examination (1, 4,
      and 8 weeks) and electroretinography (4 and 8 weeks), after which they were
      enucleated for light, scanning, and transmission electron microscopy. RESULTS:
      Based on intraoperative findings and postoperative scanning electron microscopy,
      eyes receiving intravitreal dispase exhibited a higher incidence of PVD compared
      to eyes receiving PBS (P = 0.029). Electroretinographic responses recorded at
      postoperative weeks 4 and 8 were similar in both dispase and PBS eyes compared to
      the unoperated fellow eyes. Clinical examinations, including indirect
      ophthalmoscopy, were indistinguishable between the PBS eyes and 11 of 12 eyes in
      the dispase group. Light and transmission electron microscopy demonstrated no
      differences in the retina between the dispase eyes and the PBS operated controls.
      CONCLUSION: Dispase is a useful adjunct in facilitating surgical creation of a
      PVDin young pig eyes.

PMID- 11508879
TI  - Highly active antiretroviral therapy-associated regression of cytomegalovirus
      retinitis: long-Term results in a small case series.
AB  - PURPOSE: To report the stability of acquired immunodeficiency syndrome (AIDS)
      associated cytomegalovirus (CMV) retinitis lesions that have undergone regression
      in the absence of specific anti-CMV medications owing to highly active
      antiretroviral therapy (HAART)-generated immune recovery. METHODS: The initial
      examination revealed HAART-associated regression of CMV retinitis lesions in
      eight subjects at two institutions. Patients were monitored for recurrences of
      CMV activity. CD4+ T-lymphocyte counts and human immunodeficiency virus (HIV)
      loads were measured. RESULTS: All patients had positive initial responses to
      HAART with an average HIV load decrease of 2.26 log units (range 0.3-5.57). Mean
      CD4+ T-lymphocyte count at baseline was 45.6 (range 4-107) and increased by an
      average of 132.5 (range 7-266) within the first 2 to 4 months of HAART. Patients
      were observed for an average of 15.5 months (range 11-20 months). Six subjects
      had a vigorous and sustained response to therapy, achieving an average HIV load
      of 9,400 copies/mL (3.32 log10 decrease) and CD4+ T-lymphocyte count of 158.2
      cells/microL. These patients had no CMV retinitis progression. By contrast, two
      others who attained an average log10 decrease of only 0.48 had modest and short
      lived increases in the CD4+ T-lymphocyte count. These patients experienced
      reactivation of CMV retinitis after 5 and 7 months, respectively. CONCLUSIONS:
      Regressed CMV retinitis may remain healed for long periods. However, failure of
      HAART to induce substantial decreases in HIV load may predict poor or
      unsustainable rises in the CD4+ T-lymphocyte count and presage recurrence of CMV
      retinitis. Vigilance in ophthalmic examinations is especially mandatory in these
      subjects.

PMID- 11508880
TI  - Acute retinal necrosis in children caused by herpes simplex virus.
AB  - PURPOSE: To report the diagnosis, management, and outcome of acute retinal
      necrosis syndrome in children. METHOD: Case series of three consecutive children
      aged 11 years and younger who were diagnosed with acute retinal necrosis. In
      addition to full ocular and systemic examinations, the children underwent
      vitreous biopsy (Patients 1 and 2) or aqueous tap (Patient 3) for polymerase
      chain reaction analysis. RESULTS: All patients had unilateral retinitis that was
      associated with preexisting chorioretinal scars, and two patients (Patients 1 and
      3) had concurrent extraocular central nervous system abnormalities. Intraocular
      herpes simplex virus was detected in all three children: Type 1 in Patient 1 and
      Type 2 in Patients 2 and 3. In addition, all three children had a history of
      extraocular herpes simplex virus infection. CONCLUSIONS: Retinitis associated
      with preexisting chorioretinal scars and detectable intraocular herpes simplex
      virus on polymerase chain reaction was common to all three children with acute
      retinal necrosis.

PMID- 11508881
TI  - Choroidal infarction, anterior ischemic optic neuropathy, and central retinal
      artery occlusion from polyarteritis nodosa.
AB  - PURPOSE: Ocular ischemia from polyarteritis nodosa (PAN) is rare. The authors
      present a case of multifocal ocular infarction from PAN. METHODS AND RESULTS: A
      70-year-old woman developed hand and foot numbness followed by intermittent
      blurred vision and binocular horizontal diplopia. Two weeks later, she suddenly
      lost vision in the right eye from a central retinal artery occlusion and then
      developed a left anterior ischemic optic neuropathy and bilateral triangular
      choroidal abnormalities consistent with infarction. Her erythrocyte sedimentation
      rate and C-reactive protein were elevated. Although giant cell arteritis was
      suspected, a multiple mononeuropathy was demonstrated by electromyogram and nerve
      conduction velocity studies. Biopsy specimens from her sural nerve and biceps
      muscle showed a necrotizing vasculitis with fibrinoid necrosis, consistent with
      PAN. CONCLUSIONS: Polyarteritis nodosa can produce ischemia of a variety of
      ocular structures, including the retina, choroid, and optic nerve. In our
      patient, all three structures were affected. To our knowledge, this is the first
      reported case of the triangular sign of Amalric in PAN.

PMID- 11508882
TI  - Findings on retinal topography and thickness mapping in age-related macular
      degeneration.
AB  - PURPOSE: To report alterations in the retinal topography and thickness in typical
      cases of age-related macular degeneration (ARMD). METHODS: An optical imaging
      system was applied to patients with ARMD with alterations in the retinal
      structures. The system generates a series of 20 optical section images that
      encompass a 2 mm x 2 mm retinal area. The optical sections are digitized and
      analyzed to provide topographic maps of the vitreo-retinal and chorio-retinal
      surfaces and the retinal thickness. RESULTS: Retinal topography and thickness
      mapping in a normal eye corresponded to normal anatomy. Topographic mapping in a
      patient with confluent drusen indicated elevation of the vitreo-retinal surface.
      Retinal topography in a patient with retinal pigment epithelium detachment
      displayed localized elevation of the chorio-retinal surface. The thickness map in
      a patient with geographic atrophy of the retinal pigment epithelium revealed
      retinal thinning. In the patients with choroidal neovascularization, the
      vitreoretinal and chorio-retinal surfaces were elevated. The chorio-retinal
      surface map in a patient with evolving disciform scar displayed topographic
      variations corresponding to the fibrovascular tissue underlying the serous
      detachment. CONCLUSION: Retinal topography and thickness mapping is useful for
      visualization and evaluation of pathologic alterations in retinal structures due
      to ARMD.

PMID- 11508883
TI  - Foveal ectopia in X-linked retinoschisis.
AB  - BACKGROUND: This study compared the position of the foveal center in patients
      with X-linked retinoschisis (XLRS) and controls and estimated the frequency of
      foveal ectopia in XLRS. METHOD: Fundus photographs of 23 patients with XLRS and
      25 controls were reviewed. The position of the foveal center relative to the
      vertical center of the optic disk was determined from magnified images and
      expressed as the angle between the disk and foveal centers, relative to the
      horizontal meridian. The shortest distance between the foveal and disk centers
      was also measured, using the horizontal disk diameter (HDD) as the relative size
      unit. RESULTS: The position of the foveal center could be determined accurately
      for 43 eyes of the 23 patients with XLRS. The foveal center was located an
      average of 4.7 degrees (standard deviation, 9.3) below and 3.2 HDD (standard
      deviation, 0.4) temporal to the vertical disk center. In 9 (21 %) of the eyes,
      the fovea was above the horizontal meridian. For the control eyes, the foveal
      center was an average of 7.8 degrees (standard deviation, 2.3) below and 2.9 HDD
      (standard deviation, 0.4) temporal to the vertical disk center. According to a
      previous definition, foveal ectopia was present in 13 (30%) of the eyes with XLRS
      and none of the control eyes (P < 0.001). CONCLUSION: Foveal ectopia occurs in at
      least 30% of eyes with XLRS. This finding may provide a useful diagnostic sign
      for XLRS and may have implications for its pathogenesis.

PMID- 11508884
TI  - Diagnostic and therapeutic challenges. A 50-year-old woman with oculocutaneous
      albinism (OCA) and Type II diabetes mellitus (DM) reported bilateral progressive
      visual loss, especially during the last month.

PMID- 11508885
TI  - An atypical posterior scleritis case: a diagnostic challenge.

PMID- 11508886
TI  - A transparent peripapillary staphyloma in pathologic myopia.

PMID- 11508887
TI  - Combined optic neuropathy and central retinal artery occlusion in miliary
      tuberculosis.

PMID- 11508888
TI  - Retinal pigment epithelial detachment in the fellow eye of a patient with
      unilateral central serous chorioretinopathy treated with steroid.

PMID- 11508889
TI  - Unintentional transplantation of autologous retinal pigment epithelium during
      limited macular translocation.

PMID- 11508890
TI  - Treatment of posterior persistent hyperplastic primary vitreous complicated by
      tractional retinoschisis in an adult.

PMID- 11508891
TI  - Retinal detachment due to macular hole after transpupillary thermotherapy of
      choroidal melanoma.

PMID- 11508892
TI  - Spontaneous closure of traumatic macular hole.

PMID- 11508893
TI  - Vitrectomy surgery for impending macular hole based on optical coherence
      tomography.

PMID- 11508894
TI  - Probably the longest prepapillary loop in the world.

PMID- 11508895
TI  - Polypoidal choroidal vasculopathy in a patient with melanocytoma of the optic
      nerve.

PMID- 11508896
TI  - Discourse-based intervention for word finding in children.
AB  - A discourse-based, contextual intervention approach for increasing children's
      word finding proficiency was evaluated. The clinician's role was to (a) identify
      overt word finding behaviors as they occurred, (2) allow their completion, and
      (c) provide appropriate feedback, including requests for associative information,
      requests for clarification, comments to confirm the appropriateness of word
      choices, and comments to facilitate discourse restructuring. Subjects were three
      9-year-old boys with diagnosed language-learning disabilities (LLD) characterized
      by word finding problems. Intervention proceeded following a within-subjects
      multiple baseline design involving three tasks: picture-elicited narratives,
      story-retelling, and conversation on familiar topics. All three subjects
      exhibited a decrease in the average number of problematic word finding behaviors
      from initial baseline to posttreatment measurement. Discourse-based intervention
      provided naturalistic contexts for the study of word finding behaviors,
      specifically effects of linguistic contexts and effects of task complexity.
      LEARNING OUTCOMES: (1) As a result of this activity, the participant will be able
      to identify and categorize children's overt word finding behaviors as they occur
      in discourse. (2) As a result of this activity, the participant will be able to
      discuss various aspects of a contextualized philosophy of learning as applied to
      language intervention. (3) As a result of this activity, the participant will be
      able to compare and contrast traditional intervention approaches for improving
      children's word finding with one discourse-based approach.

PMID- 11508897
TI  - Intelligibility of stops and fricatives in tracheoesophageal speech.
AB  - Listener accuracy in identifying voiced and voiceless stops and fricatives in
      tracheoesophageal (TE) and laryngeal speech were compared. Sixteen TE and ten
      laryngeal speakers produced ten phonemes embedded in a nonsense word in a carrier
      phrase. Four experienced listeners phonetically transcribed the experimental
      phonemes. As expected, perceptual error rates were higher for the TE samples for
      all comparisons completed. The dominant error for laryngeal samples was a
      misperception of manner of production. The dominant error for TE samples was a
      perception of voiced for voiceless phonemes. Such voicing misperceptions occurred
      more frequently for fricatives than stops. Previous studies have implicated the
      vibratory characteristics of the pharyngoesophageal (PE) segment for the voicing
      errors in TE speech. However, PE features would not fully explain why stops were
      less affected than fricatives and why the expected error was reversed for two TE
      phonemes (perceptions of voiceless for voiced consonants). LEARNING OUTCOMES: (1)
      As a result of this activity, the participant will be able to identify the most
      common listener misperceptions of tracheoesophageal speech. (2) As a result of
      this activity, the participant will be able to discuss possible reasons for the
      predominant error that occurs.

PMID- 11508898
TI  - The phonology-morphology interface in the speech of Hebrew-speaking children with
      specific language impairment.
AB  - Phonological deficits are common in children with specific language impairment
      (SLI). However, the degree to which they constitute an area of extraordinary
      difficulty, and their contribution to the morphological deficits of these
      children are largely unknown. In this investigation, we studied a group of young
      children with SLI who were acquiring Hebrew, a language in which phonology and
      morphology are closely linked. The phonology of these children lagged behind that
      of same-age peers as well as younger normally developing children matched
      according to mean number of morphemes per utterance. Furthermore, the children
      with SLI were more likely to commit phonological errors that neutralized
      important morphological distinctions in their language. These findings have
      implications for both assessment and therapy. LEARNING OUTCOMES: As a result of
      this activity, the following learning outcomes will be achieved: The participant
      will be able to: (1) describe the differences in phonology between children with
      SLI and typically developing children; (2) describe the impact ofphonological
      disorders on the assessment of the morphological systems of children with SLI;
      and (3) explain the necessary modifications to a therapy program for children
      with a combination of morphological and phonological disorders.

PMID- 11508899
TI  - Attention deficity/hyperactivity in SLI children increases risk of
      speech/language disorders in first-degree relatives: a preliminary report.
AB  - Specific language impairment (SLI) or developmental dysphasia denotes the
      inability to acquire normal expression and/or comprehension of language in the
      absence of peripheral hearing impairment, neurological disorder, and mental
      retardation. The presence of attention deficit/hyperactivity in some SLI children
      has previously been documented. This family history study used 27 SLI families,
      identified through the parents from the Dysphasia Association, to examine the
      relationship between attention deficit/hyperactivity in SLI children and the risk
      to first-degree relatives. All SLI children were clinically diagnosed with
      speech/language disorder; medical records were searched for the presence of any
      of the exclusion criteria noted above. The 13 SLI children with medical record of
      attention deficit/hyperactivity had a significantly higher chance of having first
      degree relatives with speech/language disorders than 14 SLI children without such
      record (15/27 and 4/46, respectively). This preliminary report suggests that
      additional study is warranted to investigate the relationship between
      speech/language disorders and attention deficit/hyperactivity in families of SLI
      children. LEARNING OUTCOMES: As a result of this activity, the participant will
      be able to describe the SLI phenotype, its prevalence, and complexity and to
      recognize the relationship between comorbid attention deficit/hyperactivity in
      SLI children and the risk of speech/language disorder in their relatives.

PMID- 11508900
TI  - Perceptions of communicative disorders: verification and specification of rater
      variables.
AB  - Using semantic differential scales with nine trait pairs, 600 students at three
      universities rated five descriptions, one depicting an individual without a
      disorder and four portraying individuals with communicative disorders.
      Statistical analyses indicated that the description with no disorder was rated as
      significantly less ambitious than the described articulation disorder. Other
      differences emerged when raters were divided by gender and age. Male subjects
      rated the portrayed individuals as more highly stressed than did females. A
      significant negative correlation was found for age of respondent and ratings of
      self-esteem. Results support previous research suggesting that rater gender and
      age impact perceptions of communicative disorders. LEARNING OUTCOMES: As a result
      of this activity, the participant will be able to: (1) identify the different
      means by which investigators have studied the stereotyping of people with
      communicative disorders, (2) discuss how listeners perceive those with and
      without communicative disorders, and (3) identify listener traits that may be
      associated with negative perceptions of people with communicative disorders.

PMID- 11508901
TI  - The study on the web-based Clinical Database Management System of Oriental Pulse
      Waveform.
AB  - There are many database-oriented sites on the web, which provide basic medical
      knowledge, hospital information, and medical counseling. However, there are only
      a few oriental pulse databases on the web. In this perspective, the goal of this
      study is to develop the Clinical Database Management System of Oriental Pulse
      Wave Form using the World Wide Web. Accordingly, this study has conducted
      researches in the Web-based diagnosis data management system of pulse waveform as
      well as the method of transmitting the data of pulse waveform. In order to set
      the standard for the documents of the pulse waveform of patients, the web-based
      clinical database management system has been developed.

PMID- 11508902
TI  - Design of an SHD-distributed database over IP to support telemedicine.
AB  - We have conducted tests utilizing superhigh-definition CRTs (hereafter, referred
      to as a "super high-definition image system," or "SHD ": 2,048 x 2,048 pixels, 24
      bit RGB gradation, noninterlace system) for autonomous and distributed medical
      image database systems. The system is capable of providing six times the image
      definition of a hi-vision television (HDTV). The aim in designing and testing the
      system is to enable gigabit network connectivity while displaying images on a DOS
      V machine. This paper discusses how we devised an integrated environment for
      managing and operating distributed an SHD image database to support Telemedicine
      linking with ATM, with INS-1500, and with dial-up IP connection.

PMID- 11508903
TI  - A versatile functional-anatomic image fusion method for volume data sets.
AB  - We describe and validate a volumetric three-dimensional registration method, and
      compare it to our previously validated two-dimensional/three-dimensional method.
      CT/MRI and SPECT data from 14 patients were interactively fused using a
      polynomial warping technique. Registration accuracy was confirmed visually and by
      a nonsignificant F value from multivariate analysis of the transformed landmarks,
      a significant difference of the squared sum of intensity differences between the
      transformed/untransformed and the reference volume both at the 0.05 (p > 0.05)
      confidence level and an average 31% improvement of the correlation coefficient
      and cross correlation. For the two-dimensional/three-dimensional method, ROI
      center-to-center distance ranged from 1.42 to 11.32 mm (for liver) with an
      average of 6.13 mm +/- 3.09 mm. The average ROI overlap was 92.51% with a 95%
      confidence interval of 90.20-96.88%. The new method is superior because it
      operates on the true three-dimensional volume. Both methods give good
      registration results, take 10 to 30 min, and require anatomic knowledge.

PMID- 11508904
TI  - The performance and problems of the Turkish pharmaceutical industry: is there a
      need to develop a national drug policy?
AB  - Turkey has a big pharmaceutical industry-of the drugs consumed there, 90% are
      manufactured domestically. Eighty percent of this manufacturing is run by foreign
      companies. In this study, the performance of the Turkish pharmaceutical industry
      in terms of the technology and production is examined and compared with that of
      some other countries, and the importance of the essential drugs list and national
      drug policy is discussed. At the end of the study, strategies are suggested
      toward meeting the main current challenges in the Turkish pharmaceutical
      industry.

PMID- 11508905
TI  - Effects of environmental threats on the quality of care in acute care hospitals.
AB  - This study investigates how environmental threats may adversely affect internal
      resources (slacks) and how hospitals' slack level may mediate the adverse effect
      of environmental threats on quality. Two testable hypotheses are (1) The
      environmental threat and level of organizational slack in hospitals are inversely
      related; and (2) Hospitals' slack level and quality of care are positively
      related. Both hypotheses are supported by the data in analysis of the structural
      relationships among the environmental threat, organizational slack, and quality
      of care indicators.

PMID- 11508906
TI  - Technology transfer with system analysis, design, decision making, and impact
      (Survey-2000) in acute care hospitals in the United States.
AB  - This paper provides the results of the Survey-2000 measuring technology transfer
      for management information systems in health care. The relationships with systems
      approaches, user involvement, usersatisfaction, and decision-making were measured
      and are presented. The survey also measured the levels Internet and Intranet
      presents in acute care hospitals, which will be discussed in future articles. The
      depth of the survey includes e-commerce for both business to business and
      customers. These results are compared, where appropriate, with results from
      survey 1997 and changes are discussed. This information will provide benchmarks
      for hospitals to plan their network technology position and to set goals. This is
      the first of three articles based upon the results of the Srvey-2000. Readers are
      referred to a prior article by the author that discusses the survey design and
      provides a tutorial on technology transfer in acute care hospitals.

PMID- 11508915
TI  - Why don't we know more about what we are doing?

PMID- 11508916
TI  - Life expectancy among people with cerebral palsy in Western Australia.
AB  - This report describes trends, predictors, and causes of mortality in persons with
      cerebral palsy (CP) using individuals identified by the Western Australian
      Cerebral Palsy Register and born between 1958 and 1994. Two thousand and fourteen
      people were identified (1154 males, 860 females), of whom 225 had died by 1 June
      1997. Using date-of-death data, crude and standardized mortality rates were
      estimated and predictors of mortality sought using survival analysis stratified
      by decade of birth, description of impairments, and demographic and perinatal
      variables. For those born after 1967, the cause of death profile was examined
      over time. Mortality exceeded 1% per annum in the first 5 years and declined to
      age 15 years after which it remained steady at about 0.35% for the next 20 years.
      The strongest single predictor was intellectual disability, but all forms of
      disability contributed to decreased life expectancy. Half of those with IQ/DQ
      score <20 survived to adulthood, increasing to 76% with IQ/DQ score 20-34, and
      exceeding 92% for higher scores. Severe motor impairment primarily increased the
      risk of early mortality. Despite there being 72 persons aged from 25 to 41 years
      with severe motor impairment in our data set, none had died after the age of 25
      years. Infants born after more than 32 weeks' gestation were at significantly
      higher risk of mortality than very preterm infants, accounted for by their higher
      rates of intellectual disability. No improvements in survival of persons with CP
      were seen over the study period despite advances in medical care, improved
      community awareness, and the increasing proportion of very preterm births among
      people with CP. This may be the result of improved neonatal care enabling the
      survival of infants with increasingly severe disabilities.

PMID- 11508917
TI  - Functional status of adults with cerebral palsy and implications for treatment of
      children.
AB  - This study examined the evolution of individuals with cerebral palsy (CP) from
      childhood to adulthood. Seventy-two adults with a diagnosis of CP born between
      1934 and 1980 were studied. Individuals were recruited and data comprehensively
      collected using case notes and through direct assessments of the majority of
      participants from three rehabilitation units in Bologna, Padua, and Rovigo in
      Italy. The main findings can be summarized as follows: contact with health and
      rehabilitation services was radically reduced once individuals reached adulthood;
      more individuals who were integrated into mainstream schools achieved and
      maintained literacy than those who had attended special schools; in a high number
      of participants, motor performance deteriorated once into adulthood. Independent
      walking or other forms of supported locomotion were lost in many on reaching
      adulthood. Of those who continued to walk, walking deteriorated in terms of
      distance. It was concluded that even though CP has been considered as
      predominantly a childhood pathological condition, the evolution of the effects of
      CP do not stop at 16 or 18 years of age. For this reason, the traditional child-
      (or infant-) oriented approach concentrating mainly or exclusively on the
      achievement of independent walking, may not be an ideal approach to children with
      CP. Instead a more independence-oriented therapeutic approach would be
      appropriate.

PMID- 11508918
TI  - Time costs of caring for children with severe disabilities compared with caring
      for children without disabilities.
AB  - To assess time costs of caring for children with severe disabilities in the
      community compared to caring for children without disabilities, a diary- and
      questionnaire-based study was carried out. Sixteen complete data sets were
      obtained from families with children who have disabilities (mean age 8.7 years)
      and 31 complete data sets from families with normally developing children (mean
      age 4.9 years). Diagnoses in the study group included cerebral palsy, autism,
      Sanfillipo syndrome, lissencephaly, and osteogenesis imperfecta. Items of
      personal care per waking hour were significantly greater in children with
      disabilities than non-disabled children (p<0.001). In the study group, there was
      no correlation (r=-0.12) between age and frequency of care whereas a significant
      correlation was observed between degree of disability as measured by the
      Functional Independence Measure for children (WeeFIM) and frequency of care items
      (r=0.89). Twelve of the 16 mothers in the study group were not in paid
      employment. Twelve had little or no extended family support. Benefits awarded did
      not correlate with the degree of disability as measured by the WeeFIM (r=-0.11).
      Care needs of children with severe disabilities are significantly greater than
      those of non-disabled children and do not decrease with advancing age. Mothers of
      children with disabilities are unable to work outside the home because of these
      care needs. This brings the family income, even when benefits are included, to a
      level that is less than peer families with non-disabled children. A Functional
      Disability Score may help to achieve more appropriate allocation of state
      resources.

PMID- 11508919
TI  - Influence of two different sitting positions on postural adjustments in children
      with spastic diplegia.
AB  - The present study addressed the question whether the deviant postural adjustments
      in children with spastic diplegia can be attributed to their crouched sitting
      position or primarily to their neural deficit. Postural adjustments during
      sitting in an erect and in a crouched position on a movable platform were
      assessed in 10 children, aged 3 to 7 years 6 months, with mild-to-severe forms of
      spastic diplegia and 10 age- and sex-matched control children. Multiple surface
      EMGs of neck, trunk, and leg muscles and kinematics of head, body sway, and
      pelvis were recorded during forward and backward translations. The children with
      normal motor development showed a distinct adaptation of postural adjustments to
      sitting position. The children with cerebral palsy (CP) had a deficient
      adaptational capacity which was more pronounced in the erect than in the crouched
      position. Thus, the crouched sitting position did not induce postural deficiency
      but seemed to offer a solution to the sensory-motor problem of the instability
      experienced. Children with severe diplegia exhibited a lack of direction
      specificity in the leg muscles during backward body sway, which points to a basic
      deficit in postural control. In addition, these children showed marked
      dysfunctions in the precise tuning of the postural adjustments to task-specific
      conditions. In the children with mild-to-moderate forms of CP the basic level of
      control was intact.

PMID- 11508920
TI  - Outcome of pseudoseizures in children and adolescents: a 6-year symptom survival
      analysis.
AB  - Outcome was studied of all children and adolescents with pseudoseizures without
      epilepsy, who were referred and treated as in-patients and/or day patients in the
      tertiary psychiatric ward at Birmingham Children's Hospital, UK between 1988 and
      1994. Information was derived from case-note data. Freedom from seizures for six
      months was defined as 'cure', as no recurrences after this period were noted.
      Kaplan-Meier survival analysis was used. Seventeen patients were identified: 15
      females and two males; mean age at presentation to the tertiary psychiatric
      service was 12 years 9 months (SD 26 months; range 8 years 3 months to 15 years 9
      months). Fourteen participants recovered and resumed regular school attendance.
      Three were lost to follow-up due to being referred on to other agencies before
      recovery because they became too old for the service. Recovery followed an
      exponential distribution, with a mean symptom survival time following treatment
      of 1.5 years. These results are consistent with a treatment effect. Younger age
      at presentation, female sex, having more types of seizures, and not receiving
      both in-patient and outpatient treatment were associated with better outcome. The
      deteriorating prognosis with age at treatment suggests prompt identification may
      be important in ensuring a good outcome.

PMID- 11508921
TI  - Accommodative esotropia: an unrecognized cause of hemifacial spasm in children.
AB  - Pediatric hemifacial spasm can be a sign of an intracranial tumor. We examined
      two females, ages 2 and 6 years, who presented with hemifacial spasm as an early
      sign of accommodative esotropia. Initial ophthalmologic examination disclosed
      high hyperopia without detectable esotropia. Both children developed an
      intermittent esotropia over the following month. In the first child, the
      hemifacial spasm resolved concurrent with the onset of amblyopia. In the second
      child, spectacle correction produced immediate cessation of the spasms. In both
      children, squinting to avoid diplopia produced an overflow facial movement that
      manifested as hemifacial spasm. Accommodative esotropia should be considered in
      the differential diagnosis of pediatric hemifacial spasm.

PMID- 11508922
TI  - Acute encephalopathy as a primary manifestation of haemophagocytic
      lymphohistiocytosis.
AB  - Haemophagocytic lymphohistiocytosis (HLH) is characterized anatomically by an
      infiltration of multiple tissues with lymphocytes and haemophagocytic
      histiocytes. First symptoms are usually hepatosplenomegaly, pancytopenia, and
      intractable fever. Up to 73% of those with HLH develop CNS involvement during the
      disease course. The peculiarity of the two patients presented here, a 20-month
      old Italian female and a 4-year-old Moroccan female, is that the initial
      presenting neurological symptoms mimicked an encephalitis, anticipating the
      typical systemic symptoms by 1 and 4 months. They developed progressive
      encephalopathy accompanied by status epilepticus, one child developed a secondary
      hydrocephalus. In both children it was not possible to detect an underlying
      infection or malignant disease and there were no other cases in the family that
      suggested a familial form of HLH. Diagnosis and initiation of treatment was
      delayed because of the initial encephalopathic clinical picture and the late
      onset of the typical systemic features. As early diagnosis allows better
      therapeutical approaches, haemophagocytic lymphohistiocytosis should be
      considered in children with persistent or progressive findings of encephalopathy,
      especially in the absence of identification of a plausible pathogen.

PMID- 11508923
TI  - Neonatal infarction within basal cerebral vein territory.
AB  - In this report, an unusual intracranial haemorrhage in a term male infant born to
      a mother with diabetes is explained on the basis of occlusion of both basal veins
      of Rosenthal. This diagnosis relies on anatomical location and iconographic
      aspect of the clots. Evidence that this vessel is occluded cannot be ascertained
      from ultrasound or MR angiographic techniques in the neonatal period. The basal
      vein has not been implicated in previous reports of neonatal brain haemorrhage.

PMID- 11508924
TI  - Management of cerebral palsy: equinus gait.

PMID- 11508925
TI  - Defining learning disability: what place does intelligence testing have now?
AB  - In summary, therefore, when we endeavour to make any statements on the presence
      and/or degree of learning disability in children, we need to consider carefully
      how we define our population. Intelligence testing, or some similar psychometric
      procedures should be available, but with two substantial caveats. First, the
      results of the tests must be taken in the context of the respective test
      situations, and any relevant wider child/environmental factors. In practice,
      where testing is carried out by a chartered psychologist according to standard
      protocols, these considerations are dealt with, and will be cited in the
      commentary on the test results. Second, intelligence testing, while helpful, is
      not sufficient of itself for definition. There must be evidence for early onset
      in the developmental period. Here, it is surprising in clinical practice how
      often the evidence is far from clear; population migration and resultant
      variations in practice and documentation are contributory factors here. However,
      all indications are that evidence of early onset may become even more important
      in the near future, in the face of these latter secular trends. In addition to
      intelligence testing, therefore, some measure of social functioning should be
      made, such as a Vineland assessment. It should be noted, however, that many of
      the same provisos that apply to intelligence testing apply here. While the
      combination of the two is quite robust, just as intelligence assessment alone is
      insufficient, the same applies to assessment of social functioning. Furthermore,
      the complexities of definition by service received, for example by school
      attended, must be considered carefully. To ignore a child's reception into
      special education is to miss important information, whether in terms of the
      preceding background factors or the resultant impact of experience at the school.
      But to identify or classify a child according to type of special education
      received, and to then go on to make prognostic statements on that basis, is far
      from satisfactory. Finally, there is a need to be clear about what is meant by
      defining learning disability. Social context and obstacles to integration may in
      a sense 'define' the individual's situation. But an operationalized definition of
      learning disabity, including the consideration of intelligence, remains vital.

PMID- 11508926
TI  - Comparison of survival in cerebral palsy between countries.

PMID- 11508927
TI  - Disability information improves reliability of cerebral palsy classification.

PMID- 11508929
TI  - School career of children is at risk before diagnosis of epilepsy only.

PMID- 11508930
TI  - Mechanism of action of rituximab.
AB  - The CD20 antigen is strongly and stably expressed on cells of the B-cell lineage,
      but not on stem cells, and is thus an ideal target antigen for antibody therapy
      of B-cell malignancies. Rituximab is a human-mouse chimeric monoclonal antibody
      to the CD20 antigen that kills B-cells by a number of different effector
      mechanisms. The human IgG component of the antibody is able to bind human
      complement and also interact with effector cells to kill cells by antibody
      dependent cell-mediated cytotoxicity. Some investigators have also shown direct
      effects of the antibody on human tumor cell lines expressing CD20. These effects
      include inhibition of proliferation, induction of apoptosis and increased
      sensitivity to chemotherapeutic agents, although the extent to which each of
      these mechanisms may contribute to the anti-tumor action of rituximab remains to
      be determined. Rituximab thus acts by additional mechanisms compared to
      conventional chemotherapeutic agents. The chimeric nature of the antibody results
      in minimal immunogenicity and allows repeat use. The antibody may be combined
      with conventional chemotherapy, with potential for increased efficacy with
      minimal added toxicity.

PMID- 11508931
TI  - Rituximab as first-line monotherapy in low-grade follicular lymphoma with a low
      tumor burden.
AB  - Patients with follicular lymphoma and a low tumor burden have a median overall
      survival of more than 10 years. Toxic conventional chemotherapy regimens are
      inappropriate in these patients, as they do not improve overall survival and the
      patients do not require palliation of symptoms. However, as most of these
      patients will ultimately die of their lymphoma, new therapies, with curative
      intent, are required. Rituximab is a human-mouse chimeric monoclonal antibody
      that has shown efficacy in patients with non-Hodgkin's lymphoma (NHL). The benign
      tolerability profile of rituximab makes it a suitable candidate for first-line
      treatment of follicular NHL patients with a low tumor burden. In a trial of 49
      patients, 73% achieved a clinical response (26% complete response) with rituximab
      treatment. Molecular studies showed that 57% of patients achieved molecular
      remission (clearance of the bcl-2 molecular translocation from the blood,
      evaluated by polymerase chain reaction), 62% of these remaining bcl-2- for at
      least 1 year. There was a good correlation between molecular and clinical
      responses, with patients failing to achieve a molecular response at higher risk
      of disease progression. Rituximab monotherapy is therefore an effective and well
      tolerated treatment for patients with low-grade lymphoma and a low tumor burden.

PMID- 11508932
TI  - Combination chemotherapy and rituximab.
AB  - Rituximab is a human-mouse chimeric monoclonal antibody that has demonstrated
      efficacy against non-Hodgkin's lymphoma (NHL). There is a powerful rationale for
      combining rituximab treatment with chemotherapeutic agents that have also shown
      efficacy in NHL, since the mechanisms of action are distinct and there is also
      evidence that rituximab may sensitize chemoresistant tumor cells to the actions
      of cytotoxic drugs. A study of rituximab plus cyclophosphamide, doxorubicin,
      vincristine and prednisone (CHOP) chemoimmunotherapy has been carried out in 40
      patients with low-grade NHL. In the 35 patients who completed the study, the
      overall response rate was 100%, with 63% achieving a complete response. Median
      time to progression has not yet been reached at 47.2+ months. Molecular analysis
      (polymerase chain reaction) showed that CHOP plus rituximab (unlike CHOP alone)
      could completely clear blood and bone marrow of cells containing the bcl-2 gene
      translocation, a molecular marker of NHL cells. Rituximab can therefore add to
      the efficacy of CHOP without significantly increasing toxicity. A further study
      is underway to determine whether similar efficacy with less overall toxicity can
      be achieved using rituximab in combination with fludarabine.

PMID- 11508933
TI  - Rituximab in autologous stem cell transplantation for follicular lymphoma.
AB  - Contamination of stem cell harvests with residual tumor cells is a significant
      problem hampering the success of autologous peripheral blood stem cell
      transplantation in non-Hodgkin's lymphoma (NHL). Techniques have therefore been
      introduced to attempt to remove these cells, either in vivo, prior to harvesting,
      or ex vivo, before reinfusion into the patient. Rituximab is a human-mouse
      chimeric anti-CD20 monoclonal antibody that has been administered to patients
      prior to stem cell harvesting, to purge the blood of residual malignant cells.
      Clinical studies have shown that rituximab is safe to use during stem cell
      mobilization since administration did not adversely affect the yield of CD34+
      stem cells or the functional capability of these progenitors. Rituximab was also
      effective in purging stem cell harvests of malignant cells. Translocation of the
      bcl-2 gene was found in a significantly smaller proportion of stem cell harvests
      from patients who had received a purging infusion of rituximab than controls.
      Rituximab may also be useful as salvage therapy following post-transplant relapse
      or as maintenance therapy for patients in remission. Prospective randomized
      trials will ultimately define the role of rituximab in the autologous
      transplantation setting.

PMID- 11508934
TI  - Current treatment of follicular and low-grade non-Hodgkin's lymphoma.
AB  - Patients with low-grade non-Hodgkin's lymphoma (NHL) have a median survival of 4
      8 years from diagnosis and a cause-specific survival of about 10 years.
      Radiotherapy can be curative in a small proportion of patients with very
      localized disease, but the majority of patients have advanced disease at
      diagnosis and it is not clear that any current therapy is curative in this
      situation. While in many instances patients with high-grade NHL are cured by
      chemotherapy, those with low-grade NHL, despite impressive response rates, almost
      invariably relapse. A 'watch-and-wait' strategy can therefore delay the onset of
      chemotherapy by 2-3 years, without affecting survival. Results with autologous
      stem cell transplantation have been similarly disappointing to date. Rituximab is
      a human-mouse chimeric monoclonal antibody that represents a novel approach to
      treatment of low-grade NHL, targeting malignant cells without the side effects
      associated with chemotherapy. A pivotal study has demonstrated a response rate of
      56% in relapsed or refractory low-grade NHL. The relatively benign side-effect
      profile means rituximab can be used early in the disease process, and in
      combination with chemotherapeutic regimens and autologous transplantation.
      Ongoing and future studies will define the optimal role of rituximab in treatment
      of low-grade NHL.

PMID- 11508957
TI  - Three-dimensional sound localization from a compact non-coplanar array of
      microphones using tree-based learning.
AB  - One of the various human sensory capabilities is to identify the direction of
      perceived sounds. The goal of this work is to study sound source localization in
      three dimensions using some of the most important cues the human uses. In an
      attempt to satisfy the requirements of portability and miniaturization in
      robotics, this approach employs a compact sensor structure that can be placed on
      a mobile platform. The objective is to estimate the relative sound source
      position in three-dimensional space without imposing excessive restrictions on
      its spatio-temporal characteristics and the environment structure. Two types of
      features are considered, interaural time and level differences. Their relative
      effectiveness for localization is studied, as well as a practical way of using
      these complementary parameters. A two-stage procedure was used. In the training
      stage, sound samples are produced from points with known coordinates and then are
      stored. In the recognition stage, unknown sounds are processed by the trained
      system to estimate the 3D location of the sound source. Results from the
      experiments showed under +/-3 degrees in average angular error and less than +/
      20% in average radial distance error.

PMID- 11508959
TI  - Intensity-invariance of fine time structure in basilar-membrane click responses:
      implications for cochlear mechanics.
AB  - Basilar-membrane and auditory-nerve responses to impulsive acoustic stimuli,
      whether measured directly in response to clicks or obtained indirectly using
      cross- or reverse-correlation and/or Fourier analysis, manifest a striking
      symmetry: near-invariance with stimulus intensity of the fine time structure of
      the response over almost the entire dynamic range of hearing. This paper explores
      the origin and implications of this symmetry for cochlear mechanics. Intensity
      invariance is investigated by applying the EQ-NL theorem [de Boer, Aud. Neurosci.
      3, 377-388 (1997)] to define a family of linear cochlear models in which the
      strength of the active force generators is controlled by a real-valued, intensity
      dependent parameter, gamma (with 0 < or = gamma < or = 1). The invariance of fine
      time structure is conjectured to imply that as gamma is varied the poles of the
      admittance of the cochlear partition remain within relatively narrow bands of the
      complex plane oriented perpendicular to the real frequency axis. Physically, the
      conjecture implies that the local resonant frequencies of the cochlear partition
      are nearly independent of intensity. Cochlear-model responses, computed by
      extending the model obtained by solution of the inverse problem in squirrel
      monkey at low sound levels [Zweig, J. Acoust. Soc. Am. 89, 1229-1254 (1991)] with
      three different forms of the intensity dependence of the partition admittance,
      support the conjecture. Intensity-invariance of cochlear resonant frequencies is
      shown to be consistent with the well-known "half-octave shift," describing the
      shift with intensity in the peak (or best) frequency of the basilar-membrane
      frequency response. Shifts in best frequency do not arise locally, via changes in
      the underlying resonant frequencies of the partition, but globally through the
      intensity dependence of the driving pressure. Near-invariance of fine time
      structure places strong constraints on the mechanical effects of force generation
      by outer hair cells. In particular, the symmetry requires that the feedback
      forces generated by outer hair cells (OHCs) not significantly affect the natural
      resonant frequencies of the cochlear partition. These results contradict many, if
      not most, cochlear models, in which OHC forces produce significant changes in the
      reactance and resonant frequencies of the partition.

PMID- 11508960
TI  - Intracochlear pressure measurements related to cochlear tuning.
AB  - Pressure in turn one of the scala tympani (s.t.) was measured close to the
      basilar membrane (b.m.) and at additional positions as the pressure sensor
      approached and/or withdrew from the b.m. The s.t. pressure measured within about
      100 microm of the b.m. varied rapidly in space at frequencies around the region's
      best frequency. Very close to the b.m. the s.t. pressure was tuned and scaled
      nonlinearly with sound level. The scala vestibuli (s.v.) pressure was measured at
      one position close to the stapes within seconds of the s.t. pressure and served
      primarily as a reference pressure. The driving pressure across the organ of Corti
      and the b.m. velocity were derived from the pressure data. Both were tuned and
      nonlinear. Therefore, their ratio, the specific acoustic impedance of the organ
      of Corti complex, was relatively untuned, and only subtly nonlinear. The
      impedance was inspected specifically for negative resistance (amplification) and
      resonance. Both were detected in some instances; taken as a whole, the current
      results constrain the possibilities for these qualities.

PMID- 11508961
TI  - Auditory nerve fiber responses to electric stimulation: modulated and unmodulated
      pulse trains.
AB  - Many modern cochlear implants use sound processing strategies that stimulate the
      cochlea with modulated pulse trains. Rubinstein et al. [Hear. Res. 127, 108
      (1999)] suggested that representation of the modulator in auditory nerve
      responses might be improved by the addition of a sustained, high-rate,
      desynchronizing pulse train (DPT). In addition, activity in response to the DPT
      may mimic the spontaneous activity (SA) in a healthy ear. The goals of this study
      were to compare responses of auditory nerve fibers in acutely deafened,
      anesthetized cats elicited by high-rate electric pulse trains delivered through
      an intracochlear electrode with SA, and to measure responses of these fibers to
      amplitude-modulated pulse trains superimposed upon a DPT. Responses to pulse
      trains showed variability from presentation to presentation, but differed from SA
      in the shape of the envelope of the interval histogram (IH) for pulse rates above
      4.8 kpps (kilo pulses per second). These IHs had a prominent mode near 5 ms that
      was followed by a long tail. Responses to modulated biphasic pulse trains
      resembled responses to tones in intact ears for small (<10%) modulation depths,
      suggesting that acousticlike responses to sinusoidal stimuli might be obtained
      with a DPT. However, realistic responses were only observed over a narrow range
      of levels and modulation depths. Improved coding of complex stimulus waveforms
      may be achieved by signal processing strategies for cochlear implants that
      properly incorporate a DPT.

PMID- 11508962
TI  - Optimal focusing by spatio-temporal inverse filter. I. Basic principles.
AB  - A focusing technique based on the inversion of the propagation operator relating
      an array of transducers to a set of control points inside a medium was proposed
      in previous work [Tanter et al., J. Acoust. Soc. Am. 108, 223-234 (2000)] and is
      extended here to the time domain. As the inversion of the propagation operator is
      achieved both in space and time, this technique allows calculation of the set of
      temporal signals to be emitted by each element of the array in order to optimally
      focus on a chosen control point. This broadband inversion process takes advantage
      of the singular-value decomposition of the propagation operator in the Fourier
      domain. The physical meaning of this decomposition is explained in a homogeneous
      medium. In particular, a definition of the number of degrees of freedom necessary
      to define the acoustic field generated by an array of limited aperture in a focal
      plane of limited extent is given. This number corresponds to the number of
      independent signals that can be created in the focal area both in space and time.
      In this paper, this broadband inverse-focusing technique is compared in
      homogeneous media with the classical focusing achieved by simple geometrical
      considerations but also with time-reversal focusing. It is shown that, even in a
      simple medium, slight differences appear between these three focusing strategies.
      In the companion paper [Aubry et al., J. Acoust. Soc. Am. 110, 48-58 (2001)] the
      three focusing techniques are compared in heterogeneous, absorbing, or complex
      media where classical focusing is strongly degraded. The strong improvement
      achieved by the spatio-temporal inverse-filter technique emphasizes the great
      potential of multiple-channel systems having the ability to apply completely
      different signal waveforms on each transducer of the array. The application of
      this focusing technique could be of great interest in various ultrasonic fields
      such as medical imaging, nondestructive testing, and underwater acoustics.

PMID- 11508963
TI  - Evidence for a behavioral significance of saccular acoustic sensitivity in
      humans.
AB  - In this article the results are reported of an experiment to provide direct
      evidence for a perceptual and behavioral significance of human saccular acoustic
      sensitivity. Ten human subjects were stimulated monaurally with 100-ms trains of
      10-ms tone pulses with pulse repetition rate of 40 Hz, and were required to rate
      the pleasantness of the stimuli on a nine-point scale. The design included three
      within-subject factors: carrier frequency (two levels, 200 and 4,000 Hz),
      intensity [13 levels from 55 to 115 dB(A) in 5-dB steps] and ear (left and
      right). For intensities above 90 dB myogenic vestibular evoked potentials (MVEP)
      were also obtained from the ipsilateral sternocleidomastoid muscle from which it
      was possible to obtain thresholds by linear regression of MVEP amplitudes against
      intensity. A further between-subjects factor was added which assessed subjects'
      attitude to vestibular sensations. The results indicate that across subjects
      there is a general trend of decreasing pleasantness with increasing intensity,
      but for the 200-Hz condition there is a significant positive departure from
      monotonicity in pleasantness (p<0.05) above the mean saccular threshold. However,
      when split by the between-subjects factor, the positive departure was only
      evident for those subjects who have a positive attitude to vestibular sensations
      (p < 0.01). Implications of these results for human responses to loud sound and
      the possible evolutionary significance of saccular acoustic sensitivity are
      discussed.

PMID- 11508964
TI  - Effects of asynchrony and ear of presentation on the pitch of mistuned partials
      in harmonic and frequency-shifted complex tones.
AB  - When a partial of a periodic complex is mistuned, its change in pitch is greater
      than expected. Two experiments examined whether these partial-pitch shifts are
      related to the computation of global pitch. In experiment 1, stimuli were either
      harmonic or frequency-shifted (25% of F0) complexes. One partial was mistuned by
      +/- 4% and played with leading and lagging portions of 500 ms each, relative to
      the other components (1 s), in both monaural and dichotic contexts. Subjects
      indicated whether the mistuned partial was higher or lower in pitch when
      concurrent with the other components. Responses were positively correlated with
      the direction of mistuning in all conditions. In experiment 2, stimuli from each
      condition were compared with synchronous equivalents. Subjects matched a pure
      tone to the pitch of the mistuned partial (component 4). The results showed that
      partial-pitch shifts are not reduced in size by asynchrony. Similar asynchronies
      are known to produce a near-exclusion of a mistuned partial from the global-pitch
      computation. This mismatch indicates that global and partial pitch are derived
      from different processes. The similarity of the partial-pitch shifts observed for
      harmonic and frequency-shifted stimuli suggests that they arise from a grouping
      mechanism that is sensitive to spectral regularity.

PMID- 11508965
TI  - Modulation detection interference: effects of concurrent and sequential
      streaming.
AB  - The presence of amplitude fluctuations in one frequency region can interfere with
      our ability to detect similar fluctuations in another (remote) frequency region.
      This effect is known as modulation detection interference (MDI). Gating the
      interfering and target sounds asynchronously is known to lead to a reduction in
      MDI, presumably because the two sounds become perceptually segregated. The first
      experiment examined the relative effects of carrier and modulator gating
      asynchrony in producing a release from MDI. The target carrier was a 900-ms, 4.3
      kHz sinusoid, modulated in amplitude by a 500-ms, 16-Hz sinusoid, with 200-ms
      unmodulated fringes preceding and following the modulation. The interferer
      (masker) was a 1-kHz sinusoid, modulated by a narrowband noise with a 16-Hz
      bandwidth, centered around 16 Hz. Extending the masker carrier for 200 ms before
      and after the signal carrier reduced MDI, regardless of whether the target and
      masker modulators were gated synchronously or were gated with onset and offset
      asynchronies of 200 ms. Similarly, when the carriers were gated synchronously,
      asynchronous gating of the modulators did not produce a release from MDI. The
      second experiment measured MDI with a synchronous target and masker and
      investigated the effect of adding a series of precursor tones, which were
      designed to promote the forming of a perceptual stream with the masker, thereby
      leaving the target perceptually isolated. Four modulated or unmodulated precursor
      tones presented at the masker frequency were sufficient to completely eliminate
      MDI. The results support the idea that MDI is due to a perceptual grouping of the
      masker and target, and show that conditions promoting sufficient perceptual
      segregation of the masker and target can lead to a total elimination of MDI.

PMID- 11508966
TI  - Formant-frequency matching between sounds with different bandwidths and on
      different fundamental frequencies.
AB  - The two experiments described here use a formant-matching task to investigate
      what abstract representations of sound are available to listeners. The first
      experiment examines how veridically and reliably listeners can adjust the formant
      frequency of a single-formant sound to match the timbre of a target single
      formant sound that has a different bandwidth and either the same or a different
      fundamental frequency (F0). Comparison with previous results [Dissard and Darwin,
      J. Acoust. Soc. Am. 106, 960-969 (2000)] shows that (i) for sounds on the same
      F0, introducing a difference in bandwidth increases the variability of matches
      regardless of whether the harmonics close to the formant are resolved or
      unresolved; (ii) for sounds on different F0's, introducing a difference in
      bandwidth only increases variability for sounds that have unresolved harmonics
      close to the formant. The second experiment shows that match variability for
      sounds differing in F0, but with the same bandwidth and with resolved harmonics
      near the formant peak, is not influenced by the harmonic spacing or by the
      alignment of harmonics with the formant peak. Overall, these results indicate
      that match variability increases when the match cannot be made on the basis of
      the excitation pattern, but match variability does not appear to depend on
      whether ideal matching performance requires simply interpolation of a spectral
      envelope or also the extraction of the envelope's peak frequency.

PMID- 11508967
TI  - Systematic distortions of auditory space perception following prolonged exposure
      to broadband noise.
AB  - Perceptual distortions referred to as aftereffects may arise following exposure
      to an adapting sensory stimulus. The study of aftereffects has a long and
      distinguished history [Kohler and Wallach, Proc. Am. Philos. Soc. 88, 269-359
      (1944)] and a range of aftereffects have been well described in sensory
      modalities such as the visual system [Barlow, in Vision: Coding and Efficiency
      (Cambridge University Press, Cambridge, 1990)]. In the visual system these
      effects have been interpreted as evidence for a population of cells or channels
      specific for certain features of a stimulus. However there has been relatively
      little work examining auditory aftereffects, particularly in respect of spatial
      location. In this study we have examined the effects of a stationary adapting
      noise stimulus on the subsequent auditory localization in the vicinity of the
      adapting stimulus. All human subjects in this study were trained to localize
      short bursts of noise in a darkened anechoic environment. Adaptation was achieved
      by presenting 4 min of continuous noise at the start of each block of trials and
      was maintained by a further 15-s noise burst between each trial. The adapting
      stimulus was located either directly in front of the subject or 30 degrees to the
      right of the midline. Subjects were required to determine the location of noise
      burst stimuli (150 ms) in the proximity of the adapting stimulus following each
      interstimulus period of adaptation. Results demonstrated that following
      adaptation there was a general radial displacement of perceived sound sources
      away from the location of the adapting stimulus. These data are more consistent
      with a channel-based or place-based process of sound localization rather than a
      simple level-based adaptation model. A simple "distribution shift" model that
      assumes an array of overlapping spatial channels is advanced to explain the
      psychophysical data.

PMID- 11508968
TI  - The effects of production and presentation level on the auditory distance
      perception of speech.
AB  - Although both perceived vocal effort and intensity are known to influence the
      perceived distance of speech, little is known about the processes listeners use
      to integrate these two parameters into a single estimate of talker distance. In
      this series of experiments, listeners judged the distances of prerecorded speech
      samples presented over headphones in a large open field. In the first experiment,
      virtual synthesis techniques were used to simulate speech signals produced by a
      live talker at distances ranging from 0.25 to 64 m. In the second experiment,
      listeners judged the apparent distances of speech stimuli produced over a 60-dB
      range of different vocal effort levels (production levels) and presented over a
      34-dB range of different intensities (presentation levels). In the third
      experiment, the listeners judged the distances of time-reversed speech samples.
      The results indicate that production level and presentation level influence
      distance perception differently for each of three distinct categories of speech.
      When the stimulus was high-level voiced speech (produced above 66 dB SPL 1 m from
      the talker's mouth), the distance judgments doubled with each 8-dB increase in
      production level and each 12-dB decrease in presentation level. When the stimulus
      was low-level voiced speech (produced at or below 66 dB SPL at 1 m), the distance
      judgments doubled with each 15-dB increase in production level but were
      relatively insensitive to changes in presentation level at all but the highest
      intensity levels tested. When the stimulus was whispered speech, the distance
      judgments were unaffected by changes in production level and only decreased with
      increasing presentation level when the intensity of the stimulus exceeded 66 dB
      SPL. The distance judgments obtained in these experiments were consistent across
      a range of different talkers, listeners, and utterances, suggesting that voice
      based distance cueing could provide a robust way to control the apparent
      distances of speech sounds in virtual audio displays.

PMID- 11508969
TI  - Dynamic articulatory model based on multidimensional invariant-feature task
      representation.
AB  - A dynamic model of articulatory movements is introduced. The research presented
      herein focuses on the method of representing the phonemic tasks, i.e., phoneme
      specific articulatory targets. Phonemic tasks in our model are formally defined
      using invariant features of articulatory posture. The invariant features used in
      the model are characterized by the linear transformation of articulatory
      variables and found using a statistical analysis of measured articulatory
      movements, in which the articulatory features with minimum variability are taken
      to be the invariant features. Articulatory movements making vocal-tract
      constrictions or relative movements among articulators reflecting task-sharing
      structures are typical examples of the features found to have low variability. In
      the trajectory formation of articulatory movements, the dimension number of the
      phonemic task is set at a smaller value than that of articulatory variables.
      Consequently, the kinematic states of the articulators are partly constrained at
      given time instants by a sequence of phonemic tasks, and there remain
      unconstrained degrees of freedom of articulatory variables. Articulatory
      movements are determined so that they simultaneously satisfy given phonemic tasks
      and dynamic smoothness constraints. The dynamic smoothness constraints coupled
      with the underspecified phonemic targets allow our model to explain contextual
      articulatory variability using context-independent phonemic tasks. Finally, the
      capability of the model for predicting actual articulatory movements is
      quantitatively investigated using empirical articulatory data.

PMID- 11508970
TI  - Generation of articulatory movements by using a kinematic triphone model.
AB  - The method described here predicts the trajectories of articulatory movements for
      continuous speech by using a kinematic triphone model and the minimum
      acceleration model. The kinematic triphone model, which is constructed from
      articulatory data obtained from experiments using an electro-magnetic
      articulographic system, is characterized by three kinematic features of a
      triphone and by the intervals between two successive phonemes in the triphone.
      After a kinematic feature of a phoneme in a given sentence is extracted, the
      minimum-acceleration trajectory that coincides with the extremum of the time
      integral of the squared magnitude of the articulator acceleration is formulated.
      The calculation of the minimum acceleration requires only linear computation. The
      method predicts both the qualitative features and the quantitative details of
      experimentally observed articulation.

PMID- 11508971
TI  - Sex-specific fundamental and formant frequency patterns in a cross-sectional
      study.
AB  - An extensive developmental acoustic study of the speech patterns of children and
      adults was reported by Lee and colleagues [Lee et al., J. Acoust. Soc. Am. 105,
      1455-1468 (1999)]. This paper presents a reexamination of selected fundamental
      frequency and formant frequency data presented in their report for ten
      monophthongs by investigating sex-specific and developmental patterns using two
      different approaches. The first of these includes the investigation of age- and
      sex-specific formant frequency patterns in the monophthongs. The second, the
      investigation of fundamental frequency and formant frequency data using the
      critical band rate (bark) scale and a number of acoustic-phonetic dimensions of
      the monophthongs from an age- and sex-specific perspective. These acoustic
      phonetic dimensions include: vowel spaces and distances from speaker centroids;
      frequency differences between the formant frequencies of males and females; vowel
      openness/closeness and frontness/backness; the degree of vocal effort; and
      formant frequency ranges. Both approaches reveal both age- and sex-specific
      development patterns which also appear to be dependent on whether vowels are
      peripheral or nonperipheral. The developmental emergence of these sex-specific
      differences are discussed with reference to anatomical, physiological,
      sociophonetic, and culturally determined factors. Some directions for further
      investigation into the age-linked sex differences in speech across the lifespan
      are also proposed.

PMID- 11508972
TI  - SIM--simultaneous inverse filtering and matching of a glottal flow model for
      acoustic speech signals.
AB  - A new method "simultaneous inverse filtering and model matching" (SIM) is
      proposed that allows one to calculate voice source measures without any user
      interaction. It is based on the discrete all-pole modeling (DAP) technique for
      inverse filtering (IF), which is modified to include a model of the glottal flow
      as integral part [LF model, Fant et al., STL-QPSR (Stockholm) 4/1985, 1-13
      (1986)]. As the correct LF parameters are initially unknown, they are estimated
      in an iterative procedure using multi-dimensional optimization techniques that
      are initialized according to the results of an exhaustive search. The error
      criteria applied reflect how well the IF is performed after the spectral
      contribution of the glottal flow has been removed. The resulting optimal LF
      parameter constellation serves as the basis to calculate 11 voice source
      measures. The performance was evaluated using synthesized signals and recordings
      of natural utterances. For the synthesized signals, the accuracy to reproduce the
      original parameters was high (correlations exceeding 0.88) for measures where the
      starting point of the glottal cycle did not enter explicitly. Errors were smaller
      compared to conventional estimation methods where the measures were estimated
      from the IF signal. The analysis of natural utterances indicates that problems
      still exist with regard to robustness, but that under advantageous conditions the
      open quotient, the speed quotient, the closing quotient, the parabolic spectral
      parameter, and the negative peak amplitude of the glottal flow derivative can
      indeed be determined automatically by the SIM method.

PMID- 11508973
TI  - Optimal focusing by spatio-temporal inverse filter. II. Experiments. Application
      to focusing through absorbing and reverberating media.
AB  - To focus ultrasonic waves in an unknown heterogeneous medium using a phased
      array, one has to calculate the optimal set of signals to be applied on the
      transducers of the array. (In most applications of ultrasound, medical imaging,
      medical therapy, nondestructive testing, the first step consists of focusing a
      broadband ultrasound beam deeply inside the medium to be investigated.) Focusing
      in a homogeneous medium simply requires to compensate for the varying focus-array
      elements geometrical distances. Nevertheless, heterogeneities in the medium, in
      terms of speed of sound, density, or absorption, may strongly degrade the
      focusing. Different techniques have been developed in order to correct such
      aberrations induced by heterogeneous media (time reversal, speckle brightness,
      for example). In the companion to this paper, a new broadband focusing technique
      was investigated: the spatio-temporal inverse filter. Experimental results
      obtained in various media, such as reverberating and absorbing media, are
      presented here. In particular, intraplate echoes suppression and high-quality
      focusing through a human skull, as well as hyper-resolution in a reverberating
      medium, will be shown. It is important to notice that all these experiments were
      performed with fully programmable multichannel electronics whose use is required
      to fully exploit the spatio-temporal technique.

PMID- 11508974
TI  - On the relationship between identification and discrimination of non-native nasal
      consonants.
AB  - To examine the relationship between the identification and discrimination of non
      native sounds, nasal consonants varying in place of articulation from Malayalam,
      Marathi, and Oriya were presented in two experiments to seven listener groups
      varying in their native nasal consonant inventory: Malayalam, Marathi, Punjabi,
      Tamil, Oriya, Bengali, and American English. The experiments consisted of a
      categorial AXB discrimination test and a forced-choice identification test with
      category goodness ratings. The identification test results were used to classify
      the non-native contrasts as one of five "assimilation types" of the Perceptual
      Assimilation Model (PAM) that are predicted to vary in their relative
      discriminability: two-category (TC), uncategorizable-categorizable (UC), both
      uncategorizable (UU), category-goodness (CG), and single-category (SC). The
      results showed that the mean percent correct discrimination scores of the
      assimilation types, but not the range of scores, were accurately predicted.
      Furthermore, differences in category goodness ratings in the CG and SC
      assimilations that were predicted to correlate with discrimination showed a weak,
      but significant correlation (r= 0.3 1, p<0.05). The implications of the results
      for models of cross-language speech perception were discussed, and an alternative
      model of cross-language speech perception was outlined, in which the
      discriminability of non-native contrasts is a function of the similarity of non
      native sounds to each other in a multidimensional, phonologized perceptual space.

PMID- 11508975
TI  - Target spectral, dynamic spectral, and duration cues in infant perception of
      German vowels.
AB  - Previous studies of vowel perception have shown that adult speakers of American
      English and of North German identify native vowels by exploiting at least three
      types of acoustic information contained in consonant-vowel-consonant (CVC)
      syllables: target spectral information reflecting the articulatory target of the
      vowel, dynamic spectral information reflecting CV- and -VC coarticulation, and
      duration information. The present study examined the contribution of each of
      these three types of information to vowel perception in prelingual infants and
      adults using a discrimination task. Experiment 1 examined German adults'
      discrimination of four German vowel contrasts (see text), originally produced in
      /dVt/ syllables, in eight experimental conditions in which the type of vowel
      information was manipulated. Experiment 2 examined German-learning infants'
      discrimination of the same vowel contrasts using a comparable procedure. The
      results show that German adults and German-learning infants appear able to use
      either dynamic spectral information or target spectral information to
      discriminate contrasting vowels. With respect to duration information, the
      removal of this cue selectively affected the discriminability of two of the vowel
      contrasts for adults. However, for infants, removal of contrastive duration
      information had a larger effect on the discrimination of all contrasts tested.

PMID- 11508976
TI  - Category restructuring during second-language speech acquisition.
AB  - This study examined the production of English /b/ and the perception of short-lag
      English /b d g/ tokens by four groups of bilinguals who differed according to
      their age of arrival (AOA) in Canada from Italy and amount of self-reported
      native language (L1) use. A clear difference emerged between early bilinguals
      (mean AOA= 8 years) and late bilinguals (mean AOA= 20 years). The late bilinguals
      showed a stronger L1 influence than the early bilinguals did on both the
      production and perception of English stops. In experiment 2, the late bilinguals
      produced a larger percentage of prevoiced English /b/ tokens than early
      bilinguals and native English (NE) speakers did. In experiment 3, the late
      bilinguals misidentified short-lag English /b d g/ tokens as /p t k/ more often
      than the early bilinguals and NE speakers did. Experiment 4 revealed that the
      frequencies with which the bilinguals prevoiced /b d g/ in Italian and English
      were correlated. The observed differences between the early and late bilinguals
      were attributed to differences in the quantity and quality of English phonetic
      input they had received, not to a greater likelihood by the early than late
      bilinguals to establish new phonetic categories for English /b d g/.

PMID- 11508977
TI  - Effects of degradation of intensity, time, or frequency content on speech
      intelligibility for normal-hearing and hearing-impaired listeners.
AB  - Many hearing-impaired listeners suffer from distorted auditory processing
      capabilities. This study examines which aspects of auditory coding (i.e.,
      intensity, time, or frequency) are distorted and how this affects speech
      perception. The distortion-sensitivity model is used: The effect of distorted
      auditory coding of a speech signal is simulated by an artificial distortion, and
      the sensitivity of speech intelligibility to this artificial distortion is
      compared for normal-hearing and hearing-impaired listeners. Stimuli (speech plus
      noise) are wavelet coded using a complex sinusoidal carrier with a Gaussian
      envelope (1/4 octave bandwidth). Intensity information is distorted by
      multiplying the modulus of each wavelet coefficient by a random factor. Temporal
      and spectral information are distorted by randomly shifting the wavelet positions
      along the temporal or spectral axis, respectively. Measured were (1) detection
      thresholds for each type of distortion, and (2) speech-reception thresholds for
      various degrees of distortion. For spectral distortion, hearing-impaired
      listeners showed increased detection thresholds and were also less sensitive to
      the distortion with respect to speech perception. For intensity and temporal
      distortion, this was not observed. Results indicate that a distorted coding of
      spectral information may be an important factor underlying reduced speech
      intelligibility for the hearing impaired.

PMID- 11508980
TI  - Melody lead in piano performance: expressive device or artifact?
AB  - As reported in the recent literature on piano performance, an emphasized voice
      (the melody) tends to be played not only louder than the other voices, but also
      about 30 ms earlier (melody lead). It remains unclear whether pianists
      deliberately apply melody lead to separate different voices, or whether it occurs
      because the melody is played louder (velocity artifact). The velocity artifact
      explanation implies that pianists initially strike the keys simultaneously; it is
      only different velocities that make the hammers arrive at different points in
      time. The measured note onsets in these studies, mostly derived from computer
      monitored pianos, represent the hammer-string impact times. In the present study,
      the finger-key contact times are calculated and analyzed as well. If the velocity
      artifact hypothesis is correct, the melody lead phenomenon should disappear at
      the finger-key level. Chopin's Ballade op. 38 (45 measures) and Etude op. 10/3
      (21 measures) were performed on a Bosendorfer computer-monitored grand piano by
      22 skilled pianists. The hammer-string asynchronies among voices closely resemble
      the results reported in the literature. However, the melody lead decreases almost
      to zero at the finger-key level, which supports the velocity artifact hypothesis.
      In addition to this, expected onset asynchronies are predicted from differences
      in hammer velocity, if finger-key asynchronies are assumed to be zero. They
      correlate highly with the observed melody lead.

PMID- 11508981
TI  - Relationships among calcaneal backscatter, attenuation, sound speed, hip bone
      mineral density, and age in normal adult women.
AB  - The present study was undertaken in order to investigate the use of calcaneal
      ultrasonic backscatter for the application of diagnosis of osteoporosis.
      Broadband ultrasonic attenuation (BUA), speed of sound (SOS), the average
      backscatter coefficient (ABC), and the hip bone mineral density (BMD) were
      measured in calcanea in 47 women (average age: 58 years, standard deviation: 13
      years). All three ultrasound variables had comparable correlations with hip BMD
      (around 0.5). As reported previously by others, BUA and SOS were rather highly
      correlated with each other. The logarithm of the ABC was only moderately
      correlated with the other two. The three ultrasound parameters exhibited similar
      moderate negative correlations with age. These results taken collectively suggest
      that the ABC may carry important diagnostic information independent of that
      contained in BUA and SOS and, therefore, may be useful as an adjunct measurement
      in the diagnosis of osteoporosis.

PMID- 11508982
TI  - A bending wave simulator for investigating directional vibration sensing in
      insects.
AB  - Substrate vibrations are important in social and ecological interactions for many
      insects and other arthropods. Localization cues include time and amplitude
      differences among an array of vibration detectors. However, for small species
      these cues are greatly reduced, and localization mechanisms remain unclear. Here
      we describe a method of simulating the vibrational environment that facilitates
      investigation of localization mechanisms in small species. Our model species was
      the treehopper Umbonia crassicornis (Membracidae; length 1 cm), which
      communicates using bending waves that propagate along plant stems. We designed a
      simulator consisting of a length of dowel and two actuators. The actuators were
      driven with two time signals that created the relationship between slope and
      displacement characteristic of steady-state bending wave motion. Because the
      surface of the dowel does not bend, as would a natural stem, close approximation
      of bending wave motion was limited to a region in the center of the dowel. An
      example of measurements of the dynamic response of an insect on the simulator is
      provided to illustrate its utility in the study of directional vibration sensing
      in insects.

PMID- 11508983
TI  - Ultrasound-mediated disruption of cell membranes. I. Quantification of molecular
      uptake and cell viability.
AB  - Ultrasound-mediated drug delivery is a nonchemical, nonviral, and noninvasive
      method for targeted transport of drugs and genes into cells. Molecules can be
      delivered into cells when ultrasound disrupts the cell membrane by a mechanism
      believed to involve cavitation. This study examined molecular uptake and cell
      viability in cell suspensions (DU145 prostate cancer and aortic smooth muscle
      cells) exposed to varying peak negative acoustic pressures (0.6-3.0 MPa),
      exposure times (120-2000 ms), and pulse lengths (0.02-60 ms) in the presence of
      Optison (1.7% v/v) contrast agent. With increasing pressure and exposure time,
      molecular uptake of a marker compound, a calcein, increased and approached
      equilibrium with the extra cellular solution, while cell viability decreased.
      Varying pulse length produced no significant effect. All viability and molecular
      uptake measurements collected over the broad range of ultrasound conditions
      studied correlated with acoustic energy exposure. This suggests that acoustic
      energy exposure may be predictive of ultrasound's nonthermal bioeffects.

PMID- 11508985
TI  - Ultrasound-mediated disruption of cell membranes. II. Heterogeneous effects on
      cells.
AB  - Ultrasound has been shown to reversibly and irreversibly disrupt membranes of
      viable cells through a mechanism believed to involve cavitation. Because
      cavitation is both temporally and spatially heterogeneous, flow cytometry was
      used to identify and quantify heterogeneity in the effects of ultrasound on
      molecular uptake and cell viability on a cell-by-cell basis for suspensions of
      DU145 prostate cancer and aortic smooth muscle cells exposed to varying peak
      negative acoustic pressures (0.6-3.0 MPa). exposure times (120-2,000 ms), and
      pulse lengths (0.02-60 ms) in the presence of Optison (1.7% v/v) contrast agent.
      Cell-to-cell heterogeneity was observed at all conditions studied and was
      classified into three subpopulations: nominal uptake (NUP), low uptake (LUP), and
      high uptake (HUP) populations. The average number of molecules within each
      subpopulation was generally constant: 10(4)-10(5) molecules/cell in NUP,
      approximately 10(6) molecules/cell in LUP, and approximately 10(7) molecules/cell
      in HUP. However, the fraction of cells within each subpopulation showed a strong
      dependence on both acoustic pressure and exposure time. Varying pulse length
      produced no significant effect. The distribution of cells among the three
      subpopulations correlated with acoustic energy exposure, which suggests that
      energy exposure may govern the ability of ultrasound to induce bioeffects by a
      nonthermal mechanism.

PMID- 11508986
TI  - A model of echolocation of multiple targets in 3D space from a single emission.
AB  - Bats, using frequency-modulated echolocation sounds, can capture a moving target
      in real 3D space. The process by which they are able to accomplish this, however,
      is not completely understood. This work offers and analyzes a model for
      description of one mechanism that may play a role in the echolocation process of
      real bats. This mechanism allows for the localization of targets in 3D space from
      the echoes produced by a single emission. It is impossible to locate multiple
      targets in 3D space by using only the delay time between an emission and the
      resulting echoes received at two points (i.e., two ears). To locate multiple
      targets in 3D space requires directional information for each target. The
      frequency of the spectral notch, which is the frequency corresponding to the
      minimum of the external ear's transfer function, provides a crucial cue for
      directional localization. The spectrum of the echoes from nearly equidistant
      targets includes spectral components of both the interference between the echoes
      and the interference resulting from the physical process of reception at the
      external ear. Thus, in order to extract the spectral component associated with
      the external ear, this component must first be distinguished from the spectral
      components associated with the interference of echoes from nearly equidistant
      targets. In the model presented, a computation that consists of the deconvolution
      of the spectrum is used to extract the external-ear-dependent component in the
      time domain. This model describes one mechanism that can be used to locate
      multiple targets in 3D space.

PMID- 11508987
TI  - On the feasibility of remote palpation using acoustic radiation force.
AB  - A method of acoustic remote palpation, capable of imaging local variations in the
      mechanical properties of tissue, is under investigation. In this method, focused
      ultrasound is used to apply localized (on the order of 2 mm3) radiation force
      within tissue. and the resulting tissue displacements are mapped using ultrasonic
      correlation based methods. The tissue displacements are inversely proportional to
      the stiffness of the tissue, and thus a stiffer region of tissue exhibits smaller
      displacements than a more compliant region. In this paper, the feasibility of
      remote palpation is demonstrated experimentally using breast tissue phantoms with
      spherical lesion inclusions, and in vitro liver samples. A single diagnostic
      transducer and modified ultrasonic imaging system are used to perform remote
      palpation. The displacement images are directly correlated to local variations in
      tissue stiffness with higher contrast than the corresponding B-mode images.
      Relationships between acoustic beam parameters, lesion characteristics and
      radiation force induced tissue displacement patterns are investigated and
      discussed. The results show promise for the clinical implementation of remote
      palpation.

PMID- 11508988
TI  - Linear elastic properties of anisotropic open-cell foams.

PMID- 11508989
TI  - Estimation of an open-loop compact adaptive passive noise control system with
      microstructures.

PMID- 11508994
TI  - Measurement of stress-induced Ca(2+) pulses in single aequorin-transformed
      tobacco cells.
AB  - Signaling patterns measured in large cell populations are the sum of differing
      signals from separate cells, and thus, the detailed kinetics of Ca(2+) pulses can
      often be masked. In an effort to evaluate whether the cytosolic Ca(2+) pulses
      previously reported in populations of elicitor- and stress-stimulated tobacco
      cells accurately represent the pulses that occur in individual cells, a study of
      single cell Ca(2+) fluxes in stress-stimulated tobacco cells was undertaken.
      Individual aequorin-transformed cells were isolated from a tobacco suspension
      culture and placed directly on a sensitive photo-multiplier tube mounted in a
      dark chamber. Ca(2+)-dependent luminescence was then monitored after stimulation
      with hypo- or hyper-osmotic shock, cold shock, or defense elicitors
      (oligogalacturonic acid and harpin). Hypo-osmotic shock induced a biphasic Ca(2+)
      transient in 67% of the single cells tested that exhibited similar kinetics to
      the biphasic pulses measured repeatedly in 1ml cell suspensions. In contrast, 33%
      of the stimulated cells displayed Ca(2+) flux patterns that were not previously
      seen in cell suspension studies. Additionally, because only 29% of the cells
      tested responded with measurable Ca(2+) pulses to oligogalacturonic acid and 33%
      to the harpin protein, we conclude that not all cells in a suspension are
      simultaneously sensitive to stimulation with defense elicitors. In contrast, all
      cells tested responded with an immediate Ca(2+) influx after cold or hyperosmotic
      shock. We conclude that in many cases the Ca(2+) signaling patterns of single
      cells are accurately represented in the signaling patterns of large populations,
      but that single cell measurements are still required to characterize the Ca(2+)
      fluxes of the less prominent cell populations.

PMID- 11508995
TI  - Involvement of trp-2 protein in store-operated influx of calcium in fibroblasts.
AB  - Mammalian homologues of the Drosophila melanogaster transient receptor potential
      (trp) gene have been proposed to encode store-operated channels. This assertion
      essentially stays on the fact that expression of different trp proteins produces
      trans-membrane cation currents. However, the selectivity of the expressed
      channels and their mode of activation, in particular, their dependence to store
      depletion appears to be quite variable. In the present work, we adopted an anti
      sense strategy to study this question in transfected Chinese hamster ovary cells
      expressing the rat neurotensin receptor (CHO-NTR cells), a cellular model
      characterized by its very large store-dependent entry of Ca(2+). We identified
      different trp transcripts by RT-PCR, the trp-1 and trp-2 transcripts being by far
      the most abundant. CHO-NTR cells were then transfected with a mouse trp-2 anti
      sense construct (CHO-NTR-TRP2AS cells). We showed that in these cells, trp-2 mRNA
      was suppressed in comparison with cells transfected with a control plasmid. The
      store-operated entry of Ca(2+) was evaluated after store depletion by an IP(3)
      dependent mechanism (neurotensin stimulation) or by direct inhibition of the
      endoplasmic reticulum Ca(2+)ATPase (thapsigargin stimulation). In both cases,
      store-dependent entry of Ca(2+) was largely reduced in CHO-NTR-TRP2AS cells in
      comparison with control cells, suggesting that trp-2 protein might constitute a
      functional subunit of store-operated channels.

PMID- 11508996
TI  - Potentiation by propofol of the response of rat submandibular acinar cells to
      purinergic agonists.
AB  - The effect of propofol (2,6-diisopropylphenol) on the intracellular concentration
      of calcium ([Ca(2+)](i)) and on the response of rat submandibular acini to
      purinergic agonists was studied. By itself, propofol (60 to 200 microM) slowly
      increased the [Ca(2+)](i) without affecting the production of inositol
      phosphates. The increase of the [Ca(2+)](i) involved for about 50% the
      mobilization of thapsigargin-sensitive intracellular calcium pools. The rest of
      the calcium originated from a pool distinct from mitochondria. Propofol also
      increased the uptake of extracellular calcium but not manganese by a mechanism
      inhibited by nickel. The variation of the [Ca(2+)](i) by propofol provoked a
      decrease of cell volume measured by light scattering. Propofol increased the
      effect of a maximal concentration of extracellular ATP on the [Ca(2+)](i). This
      interaction could be observed when propofol and ATP were added simultaneously to
      the medium but not when propofol had been removed from the medium before adding
      ATP. Among ATP analogs, propofol only increased the response to benzoyl-ATP (Bz
      ATP). The blockade of P2X(7) receptors with oxidized ATP or Coomassie blue did
      not prevent the interaction between propofol and ATP. The effect of propofol
      could also be observed even when the concentration of ATP(4-) was decreased by
      extracellular magnesium to such a level that only P2X(4) receptors could possibly
      be activated by the nucleotide. Propofol had no effect on the uptake of
      manganese, the formation of pores and the activation of phospholipase D in
      response to a P2X(7) agonist. These results exclude an interaction with this
      receptor. It is concluded that, in rat submandibular acini, propofol can increase
      the [Ca(2+)](i) and decrease the cell volume. Propofol can also modulate the
      activation of P2X(4) receptors by extracellular nucleotides. These effects are
      observed at concentrations of propofol reached during the induction of anesthesia
      and might explain why hypersalivation has been reported as one of the side
      effects of propofol.

PMID- 11508997
TI  - Stimulation by thimerosal of histamine-induced Ca(2+) release in intact HeLa
      cells seen with aequorin targeted to the endoplasmic reticulum.
AB  - The oxidizing thiol reagent, thimerosal, has been shown to activate reversibly
      the inositol 1,4,5-trisphosphate (InsP(3)) receptor in several cell types. We
      have studied here the effects of thimerosal by monitoring the [Ca(2+)] inside the
      endoplasmic reticulum (ER) of intact HeLa cells with targeted aequorin. We show
      that thimerosal produced little effects on the ER-Ca(2+)-pump and only slightly
      increased the ER-Ca(2+)-leak in intact cells. Instead, thimerosal increased the
      sensitivity to histamine of ER-Ca(2+)-release by about two orders of magnitude,
      made the response much more prolonged at saturating histamine concentrations and
      enhanced both cytosolic and mitochondrial [Ca(2+)] responses to histamine.
      Moreover, inhibition of ER-Ca(2+)release by cytosolic [Ca(2+)] microdomains was
      fully preserved and sensitive to BAPTA-loading, and histamine-induced Ca(2+)
      release remained quantal in the presence of both thimerosal and intracellular
      BAPTA. The effects of thimerosal were reversible in the presence of
      dithiotreitol, suggesting the possible presence of a physiological redox
      regulatory mechanism. However, in permeabilized cells thimerosal potentiated
      InsP(3)-induced Ca(2+) release but oxidized glutathione had no effect. In
      addition, thimerosal increased the [Ca(2+)](ER) steady-state level in
      permeabilized cells. Thimerosal partially inhibited also plasma membrane
      Ca(2+)extrusion and increased Ca(2+)(Mn(2+)) entry through the plasma membrane,
      both phenomena contributing to increase the steady-state cytosolic [Ca(2+)].
      Thimerosal-induced Ca(2+) entry was additive to that induced by emptying of the
      ER, suggesting that store-operated Ca(2+) channels may not be involved. These
      results provide new insights on the mechanisms of activation and inactivation of
      InsP(3) receptors.

PMID- 11508998
TI  - A new Na/Ca exchanger splicing pattern identified in situ leads to a functionally
      active 70kDa NH(2)-terminal protein.
AB  - The Na/Ca exchanger (NCX) is an ubiquitous transporter that plays an important
      role in regulating cellular Ca(2+) balance. On gel electrophoresis, the NCX1
      protein migrates as two major bands of 120 and 70kDa. While the 120kDa is thought
      to represent the native protein, the nature of the 70kDa protein remains unclear.
      In this report, we describe a new NCX1 splicing pattern, identified during the
      cloning of NCX1 isoforms from human eye. The insertion of a newly identified
      sequence upstream exons B and D of the NCX1.3 isoform, generates a stop codon in
      frame with the NCX1 coding sequence, that should lead to a truncated Na/Ca
      exchanger (that we called NCX1.33) comprising only the N-terminal portion of the
      exchanger and a shortened intracellular loop. Insulin-secreting cells were stably
      transfected with NCX1.33. Overexpression was assessed at the mRNA and protein
      level, the truncated exchanger migrating as a70kDa band. Appropriate targeting to
      the plasma membrane was assessed by microfluorescence and by the increase in
      Na/Ca exchange activity. The results of the present study constitute a clear
      piece of evidence indicating that the Na/Ca exchanger 70kDa protein corresponds
      to the N-terminal portion of the exchanger, and is functionally active.

PMID- 11508999
TI  - Calcium-induced calcium release in neurosecretory insect neurons: fast and slow
      responses.
AB  - The dynamics of intracellular free Ca(2+)([Ca(2+)](i)) changes were investigated
      in dorsal unpaired median (DUM) neurons of the cockroach Periplaneta americana.
      Activation of voltage-gated Ca(2+) channels caused a steep increase in
      [Ca(2+)](i). Depolarizations lasting for < 100ms led to Ca(2+) release from
      intracellular stores as is indicated by the finding that the rise of [Ca(2+)](i)
      was greatly reduced by the antagonists of ryanodine receptors, ryanodine and
      ruthenium red. There is a resting Ca(2+)current which is potentiated on
      application of a neuropeptide, Neurohormone D (NHD), a member of the adipokinetic
      hormone family. Ca(2+) influx enhanced in this way again caused a rise of
      [Ca(2+)](i) sensitive to ryanodine and ruthenium red. Such rises developed and
      relaxed much more slowly than the depolarization-induced signals. Ca(2+)responses
      similar to those induced by NHD were obtained with the ryanodine receptor
      agonists caffeine (20mM) and cADP-ribose (cADPR, 100nM). These Ca(2+) responses,
      however, varied considerably in size and kinetics, and part of the cells did not
      respond at all to caffeine or cADPR. Such cells, however, produced Ca(2+) rises
      after having been treated with NHD. Thus, the variability of Ca(2+) signals might
      be caused by different filling states of Ca(2+) stores, and the resting Ca(2+)
      current seems to represent a source to fill empty Ca(2+) stores. In line with
      this notion, block of the endoplasmic Ca(2+) pump by thapsigargin (1 microM)
      produced either no or largely varying Ca(2+) responses. The Ca(2+) signals
      induced by caffeine and cADPR displayed different sensitivity to ryanodine
      receptor blockers. cADPR failed to elicit any response when ryanodine or
      ruthenium red were present. By contrast, the response to caffeine, in the
      presence of ryanodine, was only reduced by about 50% and, in the presence of
      ruthenium red, it was not at all reduced. Thus, there may be different types of
      Ca(2+) release channels. Block of mitochondrial Ca(2+) uptake with carbonyl
      cyanide m -chlorophenylhydrazone (CCCP, 1 microM) completely abolished cADPR
      induced Ca(2+) signals, but it did not affect the caffeine-induced signals. Taken
      together our findings seem to indicate that there are different stores using
      different Ca(2+) uptake pathways and that some of these pathways involve
      mitochondria.

PMID- 11509000
TI  - Venom from Anemesia species of spider modulates high voltage-activated Ca(2+)
      currents from rat cultured sensory neurones and excitatory post synaptic currents
      from rat hippocampal slices.
AB  - The actions of crude venom from Anemesia species of spider were investigated in
      cultured dorsal root ganglion neurones from neonatal rats and hippocampal slices.
      Using mass spectrometry (MALDI-TOF MS), 10-12 distinct peptides with masses
      between about 3 and 10kDa were identified in the crude spider venom. At a
      concentration of 5 microg/ml crude Anemesia venom transiently enhanced the mean
      peak whole cell voltage-activated Ca(2+) current in a voltage-dependent manner
      and potentiated transient increases in intracellular Ca(2+) triggered by 30mM KCI
      as measured using Fura-2 fluorescence imaging. Additionally, 5-8 microg/ml
      Anemesia venom increased the amplitude of glutamatergic excitatory postsynaptic
      currents evoked in hippocampal slices. Omega-Conotoxin GVIA (1 microM) prevented
      the increase in voltage-activated Ca(2+) currents produced by Anemesia venom.
      This attenuation occurred when the cone shell toxin was applied before or after
      the spider venom. Anemesia venom (5 microg/ml) created no significant change in
      evoked action potentials but produced modest but significant inhibition of
      voltage-activated K(+) currents. At a concentration of 50 microg/ml Anemesia
      venom only produced reversible inhibitory effects, decreasing voltage-activated
      Ca(2+) currents. However, no significant effects on Ca(2+) currents were observed
      with a concentration of 0.5 microg/ml. The toxin(s) in the venom that enhanced
      Ca(2+) influx into sensory neurones was heat-sensitive and was made inactive by
      boiling or repetitive freeze-thawing. Boiled venom (5 microg/ml) produced
      significant inhibition of voltage-activated Ca(2+) currents and freeze-thawed
      venom inhibited Ca(2+) transients measured using Fura-2 fluorescence. Our data
      suggest that crude Anemesia venom contains components, which increased neuronal
      excitability and neurotransmission, at least in part this was mediated by
      enhancing Ca(2+) influx through N-type voltage-activated Ca(2+) channels.

PMID- 11509001
TI  - Progesterone-induced increase of sperm cytosolic calcium is enhanced by previous
      fusion of spermatozoa to prostasomes.
AB  - Ejaculated spermatozoa must undergo a number of modifications before becoming
      able to fertilize the oocyte. The interaction of sperm with other semen
      components may influence these phenomena; human semen contains vesicles of
      prostatic origin, called prostasomes that may fuse to sperm at slightly acidic to
      neutral pH values. Prostasomes contain calcium and it has been demonstrated that
      their fusion with spermatozoa produces a transient increase (wave) of [Ca(2+)](i)
      in these cells. The fusion process also transfers protein and lipid to
      spermatozoa. These phenomena may induce long-lasting changes of sperm properties.
      We test the hypothesis that spermatozoa, as modified by fusion, change their
      ability to undergo the progesterone-induced increase of [Ca(2+)](i) and we find
      that the increase of [Ca(2+)](i) produced by the fusion with prostasomes and by
      the stimulation with progesterone are independent and additive phenomena. We also
      find that spermatozoa present a stronger response to the progesterone-induced
      increase of [Ca(2+)](i) if they are previously made to fuse with prostasomes.
      This effect does not depend directly on the [Ca(2+)](i) increase due to fusion,
      since it is still present after the [Ca(2+)](i) has returned to resting values.

PMID- 11509002
TI  - Brain cytokine production and action in anorexia and cachexia.

PMID- 11509003
TI  - Binding of octamer factors to the murine IL-5 CLE0 in primary T-cells and a T
      cell line.
AB  - Interleukin-5 (IL-5) is an inducible T-cell derived cytokine with remarkable
      specificity for the eosinophil lineage. It is controlled at the level of
      transcription and regulation of the gene is an obvious target for therapy of
      eosinophil-dependent allergic disorders such as asthma, eczema and rhinitis.
      Using a T-cell line and primary T-cells we have shown for the first time that the
      Oct1 and Oct2 transcription factors combine to form a complex with the
      functionally critical murine IL-5 cis-regulatory element, conserved lymphokine
      element 0 (CLE0), and contribute to positive regulation of the gene. These
      results show the increasingly important role of octamer factors in regulation of
      the IL-5 gene.

PMID- 11509004
TI  - Modified peptide antagonists of interleukin 5 exhibit extended in vivo
      persistence but restricted species specificity.
AB  - AF18748 is disulphide-linked homodimeric peptide with 19 amino acids in each
      chain that antagonises the action of the eosinophil-specific cytokine,
      interleukin 5 (IL-5). We have generated a set of N-terminally truncated peptides
      derived from AF18748 and demonstrated that the first five amino acids of the
      peptide do not contribute to receptor binding activity. The shortened peptide
      blocked IL-5-dependent adhesion of eosinophils with an IC(50)of 350 pM, and had
      no effect on stimulation by IL-3, granulocyte-macrophage colony-stimulating
      factor (GM-CSF), tumour necrosis factor (TNF)-alpha or fMet-Leu-Phe. The peptides
      were rapidly broken down in mouse plasma through cleavage of a single chain of
      the dimer. However, this breakdown did not correlate with loss of biological
      activity, indicating that the asymmetric peptide fragment retains full receptor
      binding capacity. The activity of AF18748 disappeared rapidly from the blood
      following intravenous injection into mice. Coupling of polyethylene glycol to the
      N-terminus of AF18748 resulted in a moderate loss in biological potency (IC(50)30
      nM), but the resulting conjugate persisted in the circulation for more than 8 h
      after injection. Despite its high potency at the human IL-5 receptor, AF18748 was
      unable to antagonise the activity of IL-5 on murine B13 cells, or on canine
      eosinophils, indicating that the peptide is highly specific for the human IL-5
      receptor.

PMID- 11509005
TI  - Mechanism of tumour necrosis factor alpha mediated eosinophil survival.
AB  - Prolonged eosinophil survival is an essential step in the late and chronic phases
      of allergic inflammation and is regulated by the eosinophil survival cytokines.
      Our work has demonstrated that tumour necrosis factor (TNF)-alpha enhances
      survival (Trypan blue exclusion test) of human peripheral blood eosinophils from
      mildly allergic patients in a dose-dependent manner. The survival activity of TNF
      alpha was inhibited by anti-TNF-RI, anti-TNF-RII antagonist antibodies and anti
      granulocyte-monocyte colony-stimulating factor (GM-CSF) neutralizing antibodies
      but not by anti-interleukin (IL)-3 or anti-IL-5 antibodies. Furthermore, TNF
      alpha-induced GM-CSF release from eosinophils. Anti-TNF-alpha antibodies also
      inhibited GM-CSF release from eosinophils induced by rat mast cell sonicate,
      which enhances eosinophil survival. To define the signal transduction pathway
      involved in GM-CSF production, eosinophils were incubated either with various
      mitogen-activated protein kinases (MAPK) inhibitors (MEK, JNK, P38), or
      Cyclosporin A (calcineurin inhibitor), or MG-132 (proteasome inhibitor). Only the
      proteasome inhibitor significantly decreased both TNF-alpha-enhanced eosinophil
      survival (from 38.1+/-4.1% to 13.3+/-1.4%) and GM-CSF release (from 6.2+/-0.7
      pg/ml to 0.3+/-0.1 pg/ml). TNF-alpha also induced nuclear factor-kappaB (NF
      kappaB) translocation to the nucleus, an essential step in GM-CSF mRNA
      production. All these findings provide evidence that NF-kappaB is involved in TNF
      alpha-enhanced eosinophil survival through the regulation of GM-CSF production by
      eosinophils.

PMID- 11509006
TI  - Role of cytokines in cancer cachexia in a murine model of intracerebral injection
      of human tumours.
AB  - To study the role of cytokines that are relevant in cancer cachexia syndrome due
      to intracerebral tumours, mice were injected with human A431 epidermoid
      carcinoma, OVCAR3 ovarian carcinoma and GBLF glioma cells comparing intracerebral
      (i.c.) and systemic (i.p. or s.c.) routes of implantation. Anorexia and weight
      loss developed within 7-10 days in mice injected i.c. with A431 or OVCAR3 cells
      well before a large tumour developed, while i.c.-injected GBLF cells did not
      induce cachexia until day 20, when the tumour was large. By contrast, mice
      injected i.p. or s.c. developed tumours without evidence of anorexia. Thus,
      intracerebrally-growing A431 and OVCAR3 resulted in cancer cachexia independent
      of tumour mass, and we investigated their cytokine pattern. Serum levels of
      murine and human cytokines are not predictive of cancer cachexia development.
      Reverse-transcriptase polymerase chain reaction (RT-PCR) analysis revealed in the
      brain of i.c.-injected A431 tumour-bearing mice expression of human interleukin
      (IL-)1alpha, IL-1beta and LIF in all samples and IL-6 in two of four samples
      while in i.c.-injected OVCAR3 tumour-bearing animals IL-6, and LIF were detected
      in all samples and tumour necrosis factor-alpha (TNFalpha) in two of four
      samples. Only LIF was expressed in brains of mice injected with GBLF cells.
      Murine IL-6 was increased only in the brains of A431-bearing mice. Only mice
      injected i.c. simultaneously with a monoclonal antibody (mAb) directed against
      the murine IL-6 receptor and OVCAR3 cells, but not those with mAb and A431 cells,
      showed a significant increase in survival time with a partial and temporary
      attenuation of cachexia symptoms. These results suggest that IL-6 in OVCAR3 model
      may be important cachectogenic factor when centrally released by even a limited
      number of tumour cells.

PMID- 11509008
TI  - Inhibitory effect of physiological concentrations of cortisol but not estradiol
      on interleukin (IL)-6 production by human osteoblast-like cell lines with
      different constitutive IL-6 expression.
AB  - Estrogen deficiency and glucocorticoid excess are two well-known conditions that
      account for osteoporosis. Interleukin (IL)-6 plays an important role in bone
      resorption; both estrogens and glucocorticoids are credited with an inhibitory
      effect on osteoblast production of IL-6. The aim of the study was to investigate
      whether endogenous hormones, which lead to opposite changes in bone mass, have a
      common inhibitory effect upon constitutive and inducible IL-6 production by human
      osteoblast-like cells. We used two human osteosarcoma cell lines (MG-63 and Saos
      2) with a different degree of differentiation and constitutive production of IL-6
      [2587+/-536 (mean+/-SE) and 3.65+/-0.06 pg/10(6) cells, respectively]. We
      examined the effects of physiological and supraphysiological concentrations of
      17beta-estradiol (E2) and cortisol on basal and IL-1beta-induced IL-6 release in
      the medium. In all experimental conditions, cellular estrogen receptors (ERs) and
      glucocorticoid receptors (GRs) were measured by binding assay. Both MG-63 and
      Saos-2 cell lines had measurable GRs (106 300+/-24 996 and 18 100+/-3215 binding
      sites/cell, respectively) and ERs (2197+/-377 and 1261+/-66.5 binding sites/cell,
      respectively). In MG-63 cells, cortisol treatment for 20 h decreased both basal
      and IL-1beta-induced IL-6 release in a dose-dependent manner; in Saos-2 cells the
      same effect was apparent for IL-1beta-induced release. Mifepristone (RU-486) did
      function as partial agonist and antagonist of cortisol. At variance with
      cortisol, E2 did not exert any effect on IL-6 secretion. Treatment with
      1,25(OH)2D3 increased by 100-200% ER concentrations, but did not change
      ineffectiveness of E2 in modifying IL-6 production; furthermore, when E2 was
      combined with cortisol, there was no additive effect on cortisol-induced
      inhibition. The dissociation between glucocorticoid and estrogen effects observed
      in these human cell lines is a sufficiently robust phenomenon to raise questions
      about the pathogenetic role of IL-6 in osteoporosis associated with estrogen
      deficiency. Conversely inhibition of osteoblast production of IL-6 may offer an
      explanation why bone resorption is not the dominant factor in the pathogenesis of
      glucocorticoid-induced osteoporosis.

PMID- 11509007
TI  - Expression of IL-15 and IL-4 in IFN-gamma-independent control of experimental
      human Cryptosporidium parvum infection.
AB  - We have previously demonstrated interferon gamma (IFN-gamma) in intestinal mucosa
      after experimental human Cryptosporidium parvum infection, but expression was
      limited to sensitized volunteers. To characterize IFN-gamma-independent
      mechanisms in control of infection, jejunal biopsies from immunocompetent
      volunteers experimentally challenged with C. parvum were examined by in situ
      hybridization for interleukin (IL-)15 and IL-4 mRNA with confirmation by
      immunohistochemistry. Cytokine expression was correlated with prechallenge anti-
      C. parvum IgG, symptoms, oocyst shedding, and prior IFN-gamma expression data. IL
      15 expression was noted only in those without prior sensitization, who did not
      express IFN-gamma. By contrast, expression of IL-4 was associated with prior
      sensitization. IL-15 was only detected in those with symptoms (6/14 symptomatic
      vs 0/3 asymptomatic, P<0.05). Among 14 volunteers who did not express IFN-gamma,
      oocyst shedding was lower in those expressing IL-15. Overall, 14/15 volunteers
      who did not shed oocysts expressed either IFN-gamma or IL-15. There was no
      correlation between expression of IL-4 and symptoms or oocyst shedding. In
      conclusion, IL-15 expression was associated with control of oocyst shedding in
      those not expressing IFN-gamma. These data suggest that IL-15 is involved in IFN
      gamma independent mechanisms of control of human cryptosporidiosis, perhaps via
      activation of the innate immune response.

PMID- 11509009
TI  - Ontogeny of rat pulmonary alveolar macrophage function: evidence for a selective
      deficiency in il-10 and nitric oxide production by newborn alveolar macrophages.
AB  - Alveolar macrophages (AM) play a crucial role in host defence by secretion of a
      large repertoire of biological response modifiers (BRM) following challenge.
      Newborns manifest increased susceptibility to lung infections, suggesting a
      deficiency in AM-mediated host defence. Thus, we investigated the ontogeny of BRM
      production by resting and stimulated AM. We analysed the capacity of rat AM to
      produce mRNA specific for a range of cytokines including tumour necrosis factor
      alpha (TNF-alpha), interleukin (IL)-1beta, IL-6, IL-10, IL-12, IL-18, and the
      enzyme inducible nitric oxide synthase, in response to in vitro
      lipopolysaccharide (LPS) challenge. We report that production of nitric oxide by
      newborn AM under conditions of maximal stimulation was impaired. In addition,
      expression of IL-10 was only minimally upregulated in AM from newborns in
      response to LPS compared to adults. Inability to upregulate expression of IL-10
      appeared to be influenced by microenvironmental factors, since peritoneal
      macrophages from newborns responded to LPS with significant upregulation of IL
      10. Furthermore, when newborn AM were precultured in vitro, IL-10 responsiveness
      to LPS was partially restored. In contrast, cytokines such as TNF-alpha, IL-1, IL
      6, IL-12 and IL-18 appeared to be expressed at adult levels by newborn AM. These
      results demonstrate that there may be functional differences in AM of newborns
      compared to adults, and these may be specific to the tissue compartment.

PMID- 11509010
TI  - Carnitine transport by organic cation transporters and systemic carnitine
      deficiency.
AB  - The intracellular homeostasis is controlled by different membrane transporters.
      Organic cation transporters function primarily in the elimination of cationic
      drugs, endogenous amines, and other xenobiotics in tissues such as the kidney,
      intestine, and liver. Among these molecules, carnitine is an endogenous amine
      which is an essential cofactor for mitochondrial beta-oxidation. Recently, a new
      family of transporters, named OCT (organic cation transporters) has been
      described. In this minireview, we present the recent knowledge about OCT and
      focus on carnitine transport, more particularly by the OCTN2. The importance of
      this sodium-dependent carnitine cotransporter, OCTN2, comes from various recently
      reported mutations in the gene which give rise to the primary systemic carnitine
      deficiency (SCD; OMIM 212140). The SCD is an autosomal recessive disorder of
      fatty acid oxidation characterized by skeletal myopathy, progressive
      cardiomyopathy, hypoglycemia and hyperammonemia. Most of the OCTN2 mutations
      identified in humans with SCD result in loss of carnitine transport function.
      Identifying these mutations will allow an easy targeting of the SCD syndrome. The
      characteristics of the juvenile visceral steatosis (jvs) mouse, an animal model
      of SCD showing similar symptoms as humans having this genetic disorder, are also
      described. These mice have a mutation in the gene encoding the mouse carnitine
      transporter octn2. Although various OCTN carnitine transporters have been
      identified and functionally characterized, their membrane localization and
      regulation are still unknown and must be investigated. This knowledge will also
      help in designing new drugs that regulate carnitine transport activity.

PMID- 11509011
TI  - Genetic polymorphisms in drug-metabolizing enzymes and drug targets.

PMID- 11509012
TI  - Prediction of Sanfilippo phenotype severity from immunoquantification of heparan
      N-sulfamidase in cultured fibroblasts from mucopolysaccharidosis type IIIA
      patients.
AB  - Mucopolysaccharidosis type IIIA (MPS-IIIA) is an autosomal recessive lysosomal
      storage disorder caused by the deficiency of heparan-N-sulfamidase (NS; EC
      3.10.1.1), resulting in defective degradation and subsequent storage of heparan
      sulfate and leading to a clinical phenotype known as Sanfilippo syndrome. A
      sensitive and specific monoclonal/polyclonal-based immunoquantification assay has
      enabled the determination of NS protein, down to approximately 3 pg NS protein,
      in cultured fibroblasts from control and MPS-IIIA patients. Cultured skin
      fibroblasts from 15 normal controls contained 11.9 to 105 ng of NS protein/mg
      extracted cell protein, whereas NS protein ranged from "none detected" to 11
      ng/mg in fibroblasts from 35 MPS-IIIA patients. A relationship between
      genotype/phenotype and amount of NS protein present in these MPS-IIIA fibroblasts
      was established. Immunoquantification, in combination with a specific and highly
      sensitive tetrasaccharide-based assay of NS activity, enabled the determination
      of residual specific NS activity in these fibroblasts. Specific NS activity
      ranged from 28 to 1289 nmol/min/mg NS protein for MPS-IIIA patients, compared to
      870 nmol/min/mg of recombinant human NS. It is proposed that this
      immunoquantification method, in conjunction with the specific NS activity assay,
      may be used to predict clinical severity in MPS-IIIA patients, allowing for the
      selection of individuals best suited for gene- and enzyme-replacement therapy
      when these methods become available. Also proposed is that an enzyme-replacement
      therapy achieving a correction of approximately 10% of normal NS activity is
      required to avoid the onset of a Sanfilippo clinical phenotype.

PMID- 11509013
TI  - Gaucher disease and parkinsonism: a phenotypic and genotypic characterization.
AB  - Among the many phenotypes associated with Gaucher disease, the inherited
      deficiency of glucocerebrosidase, are reports of patients with parkinsonian
      symptoms. The basis for this association is unknown, but could be due to
      alterations in the gene or gene region. The human glucocerebrosidase gene,
      located on chromosome 1q21, has a nearby pseudogene that shares 96% identity.
      Immediately adjacent to the glucocerebrosidase pseudogene is a convergently
      transcribed gene, metaxin, which has a pseudogene that is located just downstream
      to the glucocerebrosidase gene. We describe a patient with mild Gaucher disease
      but impaired horizontal saccadic eye movements who developed a tremor at age 42,
      followed by rapid deterioration of her gait. A pallidotomy at age 47 was
      unsuccessful. Her motor and cognitive deterioration progressed despite enzyme
      replacement therapy. Sequencing of the glucocerebrosidase gene identified
      mutations L444P and D409H. Southern blot analysis using the enzyme SspI showed
      that the maternal allele had an additional 17-kb band. PCR amplifications and
      sequencing of this fragment demonstrated a duplication which included the
      glucocerebrosidase pseudogene, metaxin gene, and a pseudometaxin/metaxin fusion.
      Gene alterations associated with this novel rearrangement, resulting from a
      crossover between the gene for metaxin and its pseudogene, could contribute to
      the atypical phenotype encountered in this patient.

PMID- 11509014
TI  - An examination of polymorphic genes and folate metabolism in mothers affected by
      a spina bifida pregnancy.
AB  - The effect of four polymorphic genes of folate-dependent methionine biosynthesis
      have been investigated in mothers affected by a neural tube defect pregnancy
      (NTD) and matched controls. The influence of the various genotypes on total red
      cell 5-methyl-H(4)folate,5,10-methenyl-H(4)folate, and 5-formyl-H(4)folate is
      reported, as is the effect on homocysteine and radioassay folate in both serum
      and red cells. All of the single nucleotide polymorphisms studied would seem to
      contribute to the cellular folate profile in some way. From the data presented,
      and from the work of others, it is likely that C677T 5,10
      methylenetetrahydrofolate reductase is the most important of these polymorphisms.
      Control mother folate profiles seem reasonably predictive of any given methionine
      cycle mutation, but profiles in NTD mothers do not. On this basis, it seems
      likely that some other, as yet unidentified folate lesion is causal for NTD. In
      NTD-C677T 5,10-methylenetetrahydrofolate reductase in particular, indexes of
      folate depletion such as high-performance liquid chromatography (HPLC) folate
      level, oligo-gamma-glutamyl chain length, homocysteine, and radioassay folate
      values all seem to deteriorate with increased mutant allele carriage. This
      indicates that this folate polymorphism may provide a critical threshold effect
      that helps to promote NTD occurrence in the presence of another, as yet
      unidentified folate-related factor. In more general terms, on a by genotype
      basis, all 11 genotypes studied give NTD mothers a higher homocysteine compared
      to controls. Furthermore, a trend that is less universal indicates that NTD
      mothers have higher 5,10-methenyl-H(4)folate and 5-methyl-H(4)folate levels and
      lower 5-formyl-H(4)folate and H(4)PteGlu(1) levels than do controls. One of the
      most consistent, and possibly specific, differences between participant groups is
      a statistically significant elevation of 5,10-methenyl-H(4)folate in NTD mothers
      (affects three genotypes). Possible interpretations of this finding are
      discussed.

PMID- 11509015
TI  - Is the SLC7A10 gene on chromosome 19 a candidate locus for cystinuria?
AB  - One of the genes (SLC7A9) that causes cystinuria, an inborn error of amino acid
      transport, is localized to 19q13. Close examination of human genomic DNA
      sequences has identified a similar gene (SLC7A10) that also maps to the 19q13.1
      region and is highly expressed in kidney. The homologies between SLC7A9 and
      SLC7A10 are likely the result of gene duplication. SLC7A10 is known to encode a
      protein with a function similar to that of the SLC7A9 gene product. To determine
      if mutations in the SLC7A10 gene could also cause cystinuria, we characterized
      the primary genomic structure and sequenced the 11 exons and surrounding
      sequences from 10 unrelated patients with cystinuria. We identified one missense
      mutation which may account for cystinuria in one family. We also observed one
      intronic change, as well as one silent mutation, that were seen only in
      cystinuria patients. We therefore suggest that the SLC7A10 gene warrants further
      investigation as another candidate gene for cystinuria.

PMID- 11509016
TI  - A novel mutation in SURF1 causes skipping of exon 8 in a patient with cytochrome
      c oxidase-deficient leigh syndrome and hypertrichosis.
AB  - Leigh syndrome is a rare pediatric neurodegenerative disorder attributed to
      impaired mitochondrial energy metabolism. Mutations in SURF1 have been described
      in several patients with Leigh syndrome associated with cytochrome c oxidase
      deficiency. We report a new 18-bp deletion (821del18), spanning the splice donor
      junction of exon 8 of SURF1, in an infant presenting with cytochrome c oxidase
      deficient Leigh syndrome and hypertrichosis. cDNA sequencing demonstrated that
      this deletion results in a messenger lacking exon 8. RT-PCR experiments suggested
      a rapid degradation of the aberrant mRNA species from the 5'-end.

PMID- 11509017
TI  - A novel missense mutation in human lactate dehydrogenase B-subunit gene.
AB  - Reduced activity of serum lactate dehydrogenase (LDH; EC 1.1.1.27) was found in a
      male medical student during practical examinations of his own blood. Serum LDH
      isoenzyme pattern showed reductions in activities of the isoenzymes with lower
      subunit A/B ratios such as LDH1 and LDH2. These findings were indicative of a
      partial LDH-B subunit deficiency, which was confirmed in erythrocyte hemolysates
      by Western blotting. Polymerase chain reaction (PCR)-based DNA sequence analysis
      of the LDH-B subunit gene revealed a heterozygous nucleotide change: a guanine to
      adenine substitution in codon 69 (GGG --> GAG) at the third exon of the LDH-B
      subunit gene that resulted in a glycine to glutamic acid substitution (G69E). The
      mutation was confirmed by PCR-restriction fragment length polymorphism (RFLP)
      analysis using a mismatched primer to introduce a new NcoI restriction site. The
      same heterozygous mutation was found in his mother but not in other family
      members. This mutation involves a residue belonging to alphaC helix in LDH-B
      subunit protein molecule that functions as an interface for other subunits.

PMID- 11509018
TI  - Cholecystokinin (CCK) gene as a possible risk factor for smoking: a replication
      in two independent samples.
AB  - BACKGROUND: CCK is a satiety neuropeptide. Animal studies have shown that both
      acute and chronic exposure to nicotine results in weight loss which is associated
      with an increase in hypothalamic CCK and that CCK antagonists ameliorate symptoms
      of nicotine withdrawal. A major detriment to smoking cessation, especially in
      women, is the fear of gaining weight. These observations suggested that genetic
      variants in the CCK gene might be a possible risk factor for smoking. METHODS: To
      test this hypothesis we examined the association of the C-45T promoter
      polymorphism in the Sp1 binding region of the CCK gene with smoking and BMI in
      two independent groups of subjects. RESULTS: Group 1 consisted of 191 Caucasian
      women participating in an obesity study. The T allele was present in 15% of women
      who had never smoked, 20% of ex-smokers, and 58% of current smokers, P < or =
      0.0014. The T allele was present in 26.8% of ever-smokers (ex-smokers + current
      smokers). There was no association with BMI. Group 2 consisted of 725 parents of
      twins from the Minnesota Twin and Family Study of substance abuse. Logistic
      regression analysis showed that a diagnosis of nicotine dependence was
      significantly associated with the T allele (P < or = 0.002) and with gender
      (males > females) (P < or = 0.001), but not with BMI (P < or = 0.68). The T
      allele was present in 15.9% of parents who had never smoked and 24.7% of ever
      smokers, very similar to the results for group 1. INTERPRETATION: These results
      are consistent with a role of the CCK gene as a risk factor for smoking.

PMID- 11509019
TI  - Molecular and structural analysis of two novel StAR mutations in patients with
      lipoid congenital adrenal hyperplasia.
AB  - Mutations in the gene encoding steroidogenic acute regulatory protein (StAR)
      cause lipoid congenital adrenal hyperplasia. We report a novel homozygous splice
      site mutation (IVS1 + 2T --> G) in STAR in two sisters (46XY, 46XX) who presented
      with primary adrenal insufficiency at birth and a novel homozygous R182H missense
      mutation in the putative lipid transfer domain of StAR in a phenotypic female
      (46XY) with adrenal failure and a parotid tumor. These cases highlight the
      importance of StAR-dependent steroidogenesis during fetal development and early
      infancy and of the critical functional role of R182 in cholesterol transport.

PMID- 11509020
TI  - Valproate induces in vitro accumulation of long-chain fatty acylcarnitines.
AB  - To elucidate the interference mechanisms of valproate (VPA) with mitochondrial
      fatty acid beta-oxidation (FAO), the profile of acylcarnitine formation was
      studied in vitro. Human fibroblasts were incubated with 0.2 mmol/L [U
      (13)C]palmitate, 0.4 mmol/L l-carnitine, +/- VPA (2 mmol/L) (96 h at 37 degrees
      C). Acylcarnitines (AC) were analyzed by GC-CI-MS. VPA induced an impaired
      production of acetylcarnitine (C2) and an increase on long-chain AC (C10 to C16)
      both in control and in FAO-deficient cell lines (VLCAD, LCHAD, MTP).

PMID- 11509021
TI  - 3-Methylcholanthrene increases phorbol 12-myristate 13-acetate-induced
      respiratory burst activity and intracellular calcium levels in common carp
      (Cyprinus carpio L) macrophages.
AB  - Phagocytic cells play a key role in the fish immune system. They secrete reactive
      oxygen species (ROS) involved in their bactericidal activity. These cells are
      highly sensitive to pollution by polycyclic aromatic hydrocarbons and other
      organic pollutants. We have investigated the intracellular mechanisms by which 3
      methylcholanthrene (3-MC) increased bactericidal activity of carp phagocytes.
      Macrophages isolated from head kidney (pronephros) and incubated 1 h with 3-MC
      enhanced their production of ROS when they were stimulated 1.25 h with phorbol 12
      myristate 13-acetate (PMA), a direct activator of protein kinase C (PKC). 3-MC
      also produced a rapid and a sustained increase in [Ca(2+)](i) (2 h minimum).
      However, the cytochrome P450 1A and Ah receptor inhibitor, alpha-naphtoflavone
      (alpha-NF), inhibited the potentiation of PMA-induced ROS production, suggesting
      3-MC metabolic activation. Moreover, alpha-NF increased [Ca(2+)](i) without
      macrophage ROS production, suggesting that some mechanism other than calcium
      release is playing a role in the stimulation of the macrophages by 3-MC. The rise
      in [Ca(2+)](i) induced by 3-MC was potentiated by the inhibitor of the
      endoplasmic reticulum calcium ATPases, thapsigargin. And treating the cells with
      3-MC decreased the calcium mobilization caused by thapsigargin. These results
      suggest that 3-MC acts on the endoplasmic reticulum, perhaps directly on calcium
      ATPases, to increase intracellular calcium levels in carp phagocytes.

PMID- 11509022
TI  - Acute exposure of cerebellar granule neurons to ethanol suppresses stress
      activated protein kinase-1 and concomitantly induces AP-1.
AB  - The current studies were designed to examine the mechanisms of acute effects of
      ethanol on cerebellar granule neurons (CGNs) during neurodevelopment, with
      specific reference to activator protein-1 (AP-1). CGNs, isolated from 3-day-old
      Sprague-Dawley rats and cultured for 3 days, were exposed to 0, 22.5, and 100 mM
      ethanol for 1 h. Gel shift assays performed on the nuclear protein extracts
      showed increased AP-1 and heat shock factor-1 (HSF-1) transcriptional activation
      in response to ethanol. Western blots and RT-PCR showed increased c-JUN and
      phosphorylated c-JUN (serine 73) protein, as well as c-jun mRNA. Ethanol
      paradoxically decreased the activity of stress-activated protein kinase-1 (SAPK
      1) while increasing p44 and p42 mitogen-activated protein kinase (MAPK) activity.
      The protein synthesis-inhibiting and SAPK-1 activity-inducing antibiotic,
      anisomycin (30 and 500 microM) decreased AP-1 transcriptional activation to 47
      and 23% of control values, respectively. The anisomycin effect was enhanced in
      the presence of 100 mM ethanol. Similarly, cycloheximide decreased ethanol
      induced AP-1 transcriptional activation. Pretreatment with the MAPK kinase (MEK)
      pathway inhibitor PD98059 resulted in decreases in both ethanol-induced and
      control AP-1 DNA binding. Thus this acute ethanol-induced increased AP-1
      transcriptional activation requires protein synthesis and involves MEK
      independent increased MAPK phosphorylation, on the one hand, and decreased SAPK-1
      activity on the other. The ethanol effect is thus ascribed to the activities of
      alternate kinase pathways and/or the inhibition of (a) protein phosphatase(s).
      Exposure of CGNs to ethanol for 24 h resulted in decreased AP-1 DNA binding, an
      observation that could have consequences for overall neuronal function under
      chronic exposure conditions.

PMID- 11509023
TI  - Epididymal epithelial cell involution following a single intraperitoneal
      administration of ethane dimethanesulfonate in the goat (Capra hircus).
AB  - Ethane dimethanesulfonate (EDS) selectively destroys Leydig cells in rats and a
      few other smaller animal species but not in mice and quail. In the teleost fish,
      it stimulates testicular activity instead. It also causes formation of sperm
      granulomas, reduction of sperm fertilizing ability, and destruction of clear
      cells in the epididymis. Investigations involving larger animal species are
      scanty. We have previously reported that EDS has no effect on goat Leydig cells
      but appears to have a direct cytotoxic effect on the seminiferous epithelium.
      This study was therefore designed to investigate the effects of EDS on goat
      epididymal cytoarchitecture. EDS was administered intraperitoneally at two dose
      levels, 75 and 25 mg/kg body wt. The former dose was rather toxic, killing three
      of five goats in this group within 24 h whereas the latter dose was well
      tolerated. Six days after treatment, the goats were hemicastrated and the
      epididymis was isolated and processed for light and electron microscopy.
      Involution associated with EDS was observed in epithelial cells of all regions of
      the epididymis, each having its own specific and peculiar changes. In the caput,
      there was increased cytoplasmic density accompanied by enlarged vacuoles and
      paucity of secretory vesicles in the apical cytoplasm. The Golgi cisternae were
      dilated and disorganized and, in the basal aspect, large dense staining bodies or
      inclusions, degenerative mitochondria, and lamellated bodies were observed. In
      the corpus, large vacuoles containing flocculent materials occurred in the entire
      cell cytoplasm but were particularly numerous and large in the midcytoplasm,
      completely obliterating the Golgi area. There was a dramatic reduction in
      epithelial height in the cauda epididymis accompanied by sparse distribution of
      markedly shortened microvilli. The epithelial cells had extensively lobulated
      nuclei and disorganized cytoplasm with dilated Golgi apparatus and large
      conglomerations of tubular structures. These structural changes suggest that EDS
      causes degeneration of goat epididymal epithelial cells. These effects are likely
      to result from the direct action of the compound on the epithelium.

PMID- 11509024
TI  - Clustering of hepatotoxins based on mechanism of toxicity using gene expression
      profiles.
AB  - Microarray technology, which allows one to quantitate the expression of thousands
      of genes simultaneously, has begun to have a major impact on many different areas
      of drug discovery and development. The question remains of whether microarray
      analysis and gene expression signature profiles can be applied to the field of
      toxicology. To date, there are very few published studies showing the use of
      microarrays in toxicology and important questions remain regarding the
      predictability and accuracy of applying gene expression profiles to toxicology.
      To begin to address these questions, we have treated rats with 15 different known
      hepatotoxins, including allyl alcohol, amiodarone, Aroclor 1254, arsenic,
      carbamazepine, carbon tetrachloride, diethylnitrosamine, dimethylformamide,
      diquat, etoposide, indomethacin, methapyrilene, methotrexate, monocrotaline, and
      3-methylcholanthrene. These agents cause a variety of hepatocellular injuries
      including necrosis, DNA damage, cirrhosis, hypertrophy, and hepatic carcinoma.
      Gene expression analysis was done on RNA from the livers of treated rats and was
      compared against vehicle-treated controls. The gene expression results were
      clustered and compared to the histopathology findings and clinical chemistry
      values. Our results show strong correlation between the histopathology, clinical
      chemistry, and gene expression profiles induced by the agents. In addition, genes
      were identified whose regulation correlated strongly with effects on clinical
      chemistry parameters. Overall, the results suggest that microarray assays may
      prove to be a highly sensitive technique for safety screening of drug candidates
      and for the classification of environmental toxins.

PMID- 11509025
TI  - Persistent, low-dose 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure: effect on aryl
      hydrocarbon receptor expression in a dioxin-resistance model.
AB  - Most toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) are mediated by
      the aryl hydrocarbon receptor (AHR). A single, acute dose of TCDD can alter its
      own receptor levels thus complicating evaluation of dose-response relationships
      for AHR-mediated events. Since environmental exposure to dioxins is typically of
      a repeated low-dose nature, we examined the effect of such exposure on AHR
      expression. Three rat strains differing greatly in their sensitivity to acute
      TCDD lethality, Long-Evans (Turku AB) (L-E) (LD50 approximately 10 microg/kg);
      Sprague Dawley (SD) (LD50 approximately 50 microg/kg); and Han/Wistar (Kuopio)
      (H/W) (LD50 > 9600 microg/kg), were administered TCDD intragastrically, biweekly
      for 22 weeks producing doses equivalent to 0, 10, 30, and 100 ng/kg/day. Changes
      in hepatic AHR levels were quantitated at the protein level by radioligand
      binding and immunoblotting and at the mRNA level by RT-PCR. Cytosolic AHR protein
      was elevated at 10 or 30 ng/kg/day TCDD in SD and L-E rats; AHR mRNA was also
      elevated at these doses, suggesting a pretranslational mechanism. There was no
      apparent relationship between TCDD-induced AHR regulation and strain sensitivity
      to TCDD. Overall, "subchronic" TCDD did not greatly perturb AHR expression. The
      maintenance of relatively constant receptor levels in the face of persistent
      agonist stimulation is in contrast to the sustained depletion of AHR by TCDD
      observed in cell culture and to the fluctuations in AHR observed hours to days
      following acute TCDD exposure in vivo. Changes in AHR levels may affect dose
      response relationships; the effect of TCDD on its own receptor at environmentally
      relevant dosing schemes is therefore important to risk assessment.

PMID- 11509026
TI  - Loss of homotypic epithelial cell adhesion by selective N-cadherin displacement
      in bismuth nephrotoxicity.
AB  - The nephrotoxicity of single high doses of bismuth (Bi)-containing therapeutic
      drugs is characterized morphologically by detachment of proximal tubular
      epithelial cells (PTECs) from each other, followed by cell death. We investigated
      whether Bi nephrotoxicity is mediated by changes in the distribution of proteins
      involved in intercellular adhesion. A nephrotoxic dose of colloidal bismuth
      subcitrate (CBS; 3.0 mmol Bi/kg) was orally administrated to 10 female Wistar
      rats. After 1 h, N-cadherin had disappeared from the adherence junctions of vital
      PTECs, whereas ZO-1, a tight junction marker, remained present at the cell-cell
      border until cell death occurred after 3 h. E-Cadherin, absent in PTECs, remained
      absent. Exposure of the renal epithelial cell lines NRK-52E and LLC-PK1 to 400
      microM Bi(3+) also resulted in the disappearance of N-cadherin expression after 1
      h, whereas ZO-1, E-cadherin, and Desmoplakin expression did not resolve before
      cell death at 24 h, thus confirming in vivo results. Our results are the first to
      indicate that Bi-induced death of PTECs is preceded by redistribution of N
      cadherin and the disruption of homotypic cell adhesion.

PMID- 11509027
TI  - Interference with calcium-dependent mitochondrial bioenergetics in cardiac
      myocytes isolated from doxorubicin-treated rats.
AB  - In previous studies we showed that doxorubicin (DOX) interferes with
      mitochondrial calcium homeostasis and that cardiac mitochondria from DOX-treated
      rats express a dose-dependent, cumulative, and irreversible decrease in calcium
      loading capacity. Associated with this is an increased sensitivity to calcium
      induced cell killing of cardiac myocytes from DOX-treated rats. Because
      mitochondria play an important role in cytosolic calcium regulation, we
      questioned whether cardiac myocytes isolated from DOX-treated rats express an
      exaggerated response to interventions that increase cytosolic calcium. Adult male
      Sprague-Dawley rats received six weekly (sc) injections of either 2 mg/kg of
      doxorubicin or an equivalent volume of saline and were killed the following week.
      Cardiac myocytes were isolated and exposed in vitro to 25 microM of A23187, 20 mM
      of caffeine, or 500 microM of ouabain. A23187 and ouabain caused a dose-dependent
      increase in intracellular calcium, as measured fluorometrically with Fura-2AM. In
      the case of ouabain, the increase in cytosolic calcium was greater for myocytes
      from DOX-treated rats than for cells from control rats. With caffeine, however,
      the increase in intracellular calcium was not evident unless the mitochondria
      were depolarized. A23187 also caused depolarization of mitochondria, the extent
      of which was greater for cardiac myocytes from DOX-treated rats. All three agents
      caused depletion of cardiac myocyte ATP and cell killing, both of which were more
      profound in cells from DOX-treated rats than in controls. We suggest that by
      interfering with mitochondrial calcium regulation, long-term treatment with DOX
      renders myocytes susceptible to agents that increase cytosolic calcium,
      presumably by increasing the calcium-dependent disruption of mitochondrial
      function, leading to depletion of ATP and eventually cell death. This
      interference with mitochondrial calcium regulation may underlie the pathogenesis
      of DOX-induced cardiomyopathy.

PMID- 11509028
TI  - Identification of mucosal injury in the murine nasal airways by magnetic
      resonance imaging: site-specific lesions induced by 3-methylindole.
AB  - A magnetic resonance imaging (MRI) technique was developed to identify mucosal
      damage to the nasal passages of mice resulting from exposure to respiratory
      toxicants. 3-Methylindole (3-MI) was chosen as a model nasal toxicant because
      systemic administration of this compound in mice results in a well-characterized
      necrotizing nasal lesion that is restricted to the olfactory mucosa. MRI
      technology allows imaging of the same mice before and at time points after
      injection. In addition, morphological alterations and increases in the area of
      sinus cavity airspace can be followed as a function of dose and time following
      exposure. For 3-MI, the cross-sectional area of the sinus airspaces increased by
      1.7-fold in mice injected with 200 mg/kg and 2.6-fold in mice injected with 300
      mg/kg at 3 days after injection. Alterations in the nasal turbinates lined by
      olfactory mucosa were identified 1, 3, and 6 days postadministration of 3-MI
      using MRI. Postmortem histological examination of the nasal tissue confirmed the
      intranasal location and distribution of the 3-MI-induced lesions observed by MRI.
      MRI can be a useful technique to identify toxicant-induced mucosal injury in the
      nasal passages at an in-plane resolution less than 60 microm.

PMID- 11509029
TI  - Basal cell proliferation in female SKH-1 mice treated with alpha- and beta
      hydroxy acids.
AB  - Alpha- and beta-hydroxy acids are compounds that have been used extensively in
      cosmetic and dermatological formulations. Clinical and qualitative effects of
      alpha- and beta-hydroxy acids have been well characterized, but little is known
      about their mechanism of action or acute and chronic biochemical effects. In the
      present study, we examined the acute proliferative effects of glycolic and
      salicylic acids on cell proliferation in the epidermis of SKH-1 female mice,
      using BrdU incorporation as a marker of epidermal proliferation. In preliminary
      experiments, we observed an increase in the rate of proliferation after 3 days of
      treatment with 10% glycolic acid-containing cream and this was sustained
      throughout a 6.5-week (treatment 5 days/week) time course compared with untreated
      control animals. After each treatment with cream containing glycolic acid there
      was a wave of proliferation that was maximal 12 to 16 h (significant at p < 0.05)
      after treatment, followed by a subsequent increase in epidermal thickness at 18
      to 20 h (significant at p < 0.05). The effects of the concentration and pH level
      of glycolic acid- and salicylic acid-containing creams on the rate of
      proliferation and increases in skin thickness in SKH-1 epidermis were also
      investigated. We observed a dose-dependent increase in epidermal proliferation of
      animals treated with either glycolic or salicylic acid. A similar time-dependent
      response was observed in the epidermal thickness in animals treated with
      salicylic acid, but not with glycolic acid. Differences in pH (3.5 or 4.0) had no
      significant effect on either epidermal proliferation or skin thickness. The data
      that we present here should be useful in characterizing not only the beneficial
      but also the adverse effects that occur following acute or chronic usage of alpha
      hydroxy acids.

PMID- 11509030
TI  - Effect of JP-8 jet fuel on molecular and histological parameters related to acute
      skin irritation.
AB  - Organic chemicals such as jet fuels and solvents can cause skin irritation after
      dermal exposure. The molecular responses to these chemicals resulting in acute
      irritation are not understood well enough to establish safe exposure limits. Male
      F-344 rats were dermally exposed to JP-8 jet fuel for 1 h using Hill Top
      Chambers. Whole skin samples were collected at 0, 1, 2, 4, and 6 h after the
      beginning of the exposures, homogenized, and analyzed for interleukin (IL)-1alpha
      and inducible nitric oxide synthase (iNOS) protein and nitrite levels. IL-1alpha
      levels (determined by ELISA) ranged from approximately 11 to 34% above the 0-h
      samples over the observed time period. At 1 and 2 h, significantly higher (p <
      0.05) levels of IL-1alpha were detected when compared to the 0-h samples. Western
      blot analysis revealed significantly higher (p < 0.05) levels of iNOS at 4 and 6
      h compared to 0-h samples. Increases in IL-1alpha and iNOS expression were also
      observed in the skin immunohistochemically. Nitrite concentrations in skin
      samples were measured to estimate nitric oxide production. Although nitrite
      concentrations in the skin increased approximately 6-27% above the 0-h samples
      over the observed time period, no significant changes in nitrite levels were
      detected. Pathological changes in the skin following JP-8 exposure were evaluated
      histologically. Increased numbers of granulocytes were observed infiltrating the
      skin at 2 h and were more prominent by 6 h. These data show that a 1-h exposure
      to JP-8 results in a local inflammatory response, which can be detected by
      changes in molecular and histological parameters.

PMID- 11509031
TI  - Zinc inhibition of caspase-3 activation does not protect HeLa cells from
      apoptotic cell death.
AB  - Zinc is proposed to be antiapoptotic for it has been shown to inhibit late events
      of apoptotic pathways such as Ca(2+)/Mg(2+)-dependent endonuclease cleavage of
      chromatin DNA, poly-ADP ribose polymerase cleavage, and caspase-3 activity.
      Because caspase-3 is a critical executioner caspase in apoptosis, this study was
      undertaken to examine specifically a correlation between zinc inhibition of
      caspase-3 activation and apoptosis in HeLa cells. Cultured HeLa cells were
      exposed to 100 microM ZnCl(2) for 1 h prior to 12 h treatment with 1.0 microM
      doxorubicin (DOX), an important anticancer agent that causes apoptosis in a wide
      variety of tumor cells. Western blot analysis of HeLa cells treated with DOX for
      12 h revealed that DOX caused proteolytic activation of caspase-3 and zinc
      inhibited this activation. Interestingly, zinc did not inhibit DOX-induced
      apoptosis as measured by a terminal deoxynucleotidyl transferase-mediated dUTP
      nick-end labeling assay. Furthermore, a microculture tetrazolium assay confirmed
      that cell death occurred in the presence of zinc. These results demonstrate that
      zinc specifically inhibits DOX-induced activation of caspase-3 in HeLa cells, but
      does not suppress DOX-induced apoptosis or otherwise cell death, thus suggesting
      DOX-induced caspase-3 activation may not play a major role in overall cell death
      and/or non-caspase-3 pathways are involved in DOX-induced apoptosis in HeLa
      cells.

PMID- 11509034
TI  - Chronic myelogenous leukemia.

PMID- 11509035
TI  - Pay attention: ritalin acts much like cocaine.

PMID- 11509036
TI  - New advice for women patients about hormone therapy and the heart.

PMID- 11509037
TI  - Genetic research features murine creatures.

PMID- 11509042
TI  - Medication errors in children.

PMID- 11509043
TI  - Medication errors in children.

PMID- 11509045
TI  - Chronic fatigue syndrome and posttraumatic stress disorder.

PMID- 11509047
TI  - Smoking among Japanese physicians.

PMID- 11509049
TI  - Effects of industry sponsorship of grand rounds.

PMID- 11509051
TI  - Training in pediatric dermatology.

PMID- 11509053
TI  - A story about suicide in the Arctic.

PMID- 11509055
TI  - Relationship between asthma prevalence and income among Canadians.

PMID- 11509056
TI  - Physical activity, obesity, height, and the risk of pancreatic cancer.
AB  - CONTEXT: Diabetes mellitus and elevated postload plasma glucose levels have been
      associated with an increased risk of pancreatic cancer in previous studies. By
      virtue of their influence on insulin resistance, obesity and physical inactivity
      may increase risk of pancreatic cancer. OBJECTIVE: To examine obesity, height,
      and physical activity in relation to pancreatic cancer risk. DESIGN AND SETTING:
      Two US cohort studies conducted by mailed questionnaire, the Health Professionals
      Follow-up Study (initiated in 1986) and the Nurses' Health Study (initiated in
      1976), with 10 to 20 years of follow-up. PARTICIPANTS: A total of 46 648 men aged
      40 to 75 years and 117 041 women aged 30 to 55 years who were free of prior
      cancer at baseline and had complete data on height and weight. MAIN OUTCOME
      MEASURES: Relative risk of pancreatic cancer, analyzed by self-reported body mass
      index (BMI), height, and level of physical activity. RESULTS: During follow-up,
      we documented 350 incident pancreatic cancer cases. Individuals with a BMI of at
      least 30 kg/m(2) had an elevated risk of pancreatic cancer compared with those
      with a BMI of less than 23 kg/m(2) (multivariable relative risk [RR], 1.72; 95%
      confidence interval [CI], 1.19-2.48). Height was associated with an increased
      pancreatic cancer risk (multivariable RR, 1.81; 95% CI, 1.31-2.52 for the highest
      vs lowest categories). An inverse relation was observed for moderate activity
      (multivariable RR, 0.45; 95% CI, 0.29-0.70 for the highest vs lowest categories;
      P for trend <.001). Total physical activity was not associated with risk among
      individuals with a BMI of less than 25 kg/m(2) but was inversely associated with
      risk among individuals with a BMI of at least 25 kg/m(2) (pooled multivariable
      RR, 0.59; 95% CI, 0.37-0.94 for the top vs bottom tertiles of total physical
      activity; P for trend =.04). CONCLUSION: In 2 prospective cohort studies, obesity
      significantly increased the risk of pancreatic cancer. Physical activity appears
      to decrease the risk of pancreatic cancer, especially among those who are
      overweight.

PMID- 11509057
TI  - Use of nonprescription weight loss products: results from a multistate survey.
AB  - CONTEXT: Lifestyle changes to lose weight can be difficult; hence, both
      prescription and nonprescription diet products are appealing. Usage patterns of
      the nonprescription products phenylpropanolamine (PPA) and ephedra are of
      particular interest because of recent safety concerns. OBJECTIVE: To estimate the
      prevalence of overall and specific nonprescription weight loss product use by
      demographic characteristics, prescription diet pill use, diabetic status, and
      lifestyle choices. DESIGN AND SETTING: The Behavioral Risk Factor Surveillance
      System, a random-digit telephone survey conducted in 1998 in 5 states: Florida,
      Iowa, Michigan, West Virginia, and Wisconsin. PARTICIPANTS: Population-based
      sample of 14 679 noninstitutionalized adults 18 years or older. MAIN OUTCOME
      MEASURES: Prevalence of nonprescription weight loss product use in 1996-1998.
      RESULTS: Seven percent reported overall nonprescription weight loss product use,
      2% reported PPA use, and 1% reported ephedra product use. Overall use was
      especially common among young obese women (28.4%). Moreover, 7.9% of normal
      weight women reported use. There was no difference in nonprescription weight loss
      product use by daily consumption of fruits and vegetables; however, more users
      than nonusers reported being physically active (for those who exercised >/=30
      minutes 5 times per week, odds ratio, 1.5; 95% confidence interval, 1.2-2.0).
      Among prescription weight loss product users, 33.8% also took nonprescription
      product. CONCLUSIONS: With increasing rates of obesity, nonprescription product
      use is likely to increase. Clinicians should know about their patients' use of
      both prescription and nonprescription weight loss products.

PMID- 11509058
TI  - Cost-effectiveness of vitamin therapy to lower plasma homocysteine levels for the
      prevention of coronary heart disease: effect of grain fortification and beyond.
AB  - CONTEXT: A high homocysteine level has been identified as an independent
      modifiable risk factor for coronary heart disease (CHD) events and death. Since
      January 1998, the US Food and Drug Administration has required that all enriched
      grain products contain 140 microg of folic acid per 100 g, a level considered to
      decrease homocysteine levels. OBJECTIVES: To examine the potential effect of
      grain fortification with folic acid on CHD events and to estimate the cost
      effectiveness of additional vitamin supplementation (folic acid and
      cyanocobalamin) for CHD prevention. DESIGN AND SETTING: Cost-effectiveness
      analysis using the Coronary Heart Disease Policy Model, a validated, state
      transition model of CHD events in adults aged 35 through 84 years. Data from the
      third National Health and Nutrition Examination Survey (NHANES III) were used to
      estimate age- and sex-specific differences in homocysteine levels. INTERVENTION:
      Hypothetical comparison between a diet that includes enriched grain products
      projected to increase folic acid intake by 100 microg/d with the same diet
      without folic acid fortification; and a comparison between vitamin therapy that
      consists of 1 mg of folic acid and 0.5 mg of cyanocobalamin and the diet that
      includes grains fortified with folic acid. MAIN OUTCOME MEASURES: Incidence of
      myocardial infarction and death from CHD, quality-adjusted life-years (QALYs)
      saved, and medical costs. RESULTS: Grain fortification with folic acid was
      predicted to decrease CHD events by 8% in women and 13% in men, with comparable
      reductions in CHD mortality. The model projected that, compared with grain
      fortification alone, treating all patients with known CHD with folic acid and
      cyanocobalamin over a 10-year period would result in 310 000 fewer deaths and
      lower costs. Over the same 10-year period, providing vitamin supplementation in
      addition to grain fortification to all men aged 45 years or older without known
      CHD was projected to save more than 300 000 QALYs, to save more than US $2
      billion, and to be the preferred strategy. For women without CHD, the preferred
      vitamin supplementation strategy would be to treat all women older than 55 years,
      a strategy projected to save more than 140 000 QALYs over 10 years. CONCLUSIONS:
      Folic acid and cyanocobalamin supplementation may be cost-effective among many
      population subgroups and could have a major epidemiologic benefit for primary and
      secondary prevention of CHD if ongoing clinical trials confirm that homocysteine
      lowering therapy decreases CHD event rates.

PMID- 11509059
TI  - Should immunonutrition become routine in critically ill patients? A systematic
      review of the evidence.
AB  - CONTEXT: Several nutrients have been shown to influence immunologic and
      inflammatory responses in humans. Whether these effects translate into an
      improvement in clinical outcomes in critically ill patients remains unclear.
      OBJECTIVE: To examine the relationship between enteral nutrition supplemented
      with immune-enhancing nutrients and infectious complications and mortality rates
      in critically ill patients. DATA SOURCES: The databases of MEDLINE, EMBASE,
      Biosis, and CINAHL were searched for articles published from 1990 to 2000.
      Additional data sources included the Cochrane Controlled Trials Register from
      1990 to 2000, personal files, abstract proceedings, and relevant reference lists
      of articles identified by database review. STUDY SELECTION: A total of 326
      titles, abstracts, and articles were reviewed. Primary studies were included if
      they were randomized trials of critically ill or surgical patients that evaluated
      the effect of enteral nutrition supplemented with some combination of arginine,
      glutamine, nucleotides, and omega-3 fatty acids on infectious complication and
      mortality rates compared with standard enteral nutrition, and included clinically
      important outcomes, such as mortality. DATA EXTRACTION: Methodological quality of
      individual studies was scored and necessary data were abstracted in duplicate and
      independently. DATA SYNTHESIS: Twenty-two randomized trials with a total of 2419
      patients compared the use of immunonutrition with standard enteral nutrition in
      surgical and critically ill patients. With respect to mortality, immunonutrition
      was associated with a pooled risk ratio (RR) of 1.10 (95% confidence interval
      [CI], 0.93-1.31). Immunonutrition was associated with lower infectious
      complications (RR, 0.66; 95% CI, 0.54-0.80). Since there was significant
      heterogeneity across studies, we examined several a priori subgroup analyses. We
      found that studies using commercial formulas with high arginine content were
      associated with a significant reduction in infectious complications and a trend
      toward a lower mortality rate compared with other immune-enhancing diets. Studies
      of surgical patients were associated with a significant reduction in infectious
      complication rates compared with studies of critically ill patients. In studies
      of critically ill patients, studies with a high-quality score were associated
      with increased mortality and a significant reduction in infectious complication
      rates compared with studies with a low-quality score. CONCLUSION: Immunonutrition
      may decrease infectious complication rates but it is not associated with an
      overall mortality advantage. However, the treatment effect varies depending on
      the intervention, the patient population, and the methodological quality of the
      study.

PMID- 11509060
TI  - Risk of cardiovascular events associated with selective COX-2 inhibitors.
AB  - Atherosclerosis is a process with inflammatory features and selective
      cyclooxygenase 2 (COX-2) inhibitors may potentially have antiatherogenic effects
      by virtue of inhibiting inflammation. However, by decreasing vasodilatory and
      antiaggregatory prostacyclin production, COX-2 antagonists may lead to increased
      prothrombotic activity. To define the cardiovascular effects of COX-2 inhibitors
      when used for arthritis and musculoskeletal pain in patients without coronary
      artery disease, we performed a MEDLINE search to identify all English-language
      articles on use of COX-2 inhibitors published between 1998 and February 2001. We
      also reviewed relevant submissions to the US Food and Drug Administration by
      pharmaceutical companies. Our search yielded 2 major randomized trials, the Vioxx
      Gastrointestinal Outcomes Research Study (VIGOR; 8076 patients) and the Celecoxib
      Long-term Arthritis Safety Study (CLASS; 8059 patients), as well as 2 smaller
      trials with approximately 1000 patients each. The results from VIGOR showed that
      the relative risk of developing a confirmed adjudicated thrombotic cardiovascular
      event (myocardial infarction, unstable angina, cardiac thrombus, resuscitated
      cardiac arrest, sudden or unexplained death, ischemic stroke, and transient
      ischemic attacks) with rofecoxib treatment compared with naproxen was 2.38 (95%
      confidence interval, 1.39-4.00; P =.002). There was no significant difference in
      cardiovascular event (myocardial infarction, stroke, and death) rates between
      celecoxib and nonsteroidal anti-inflammatory agents in CLASS. The annualized
      myocardial infarction rates for COX-2 inhibitors in both VIGOR and CLASS were
      significantly higher than that in the placebo group of a recent meta-analysis of
      23 407 patients in primary prevention trials (0.52%): 0.74% with rofecoxib (P
      =.04 compared with the placebo group of the meta-analysis) and 0.80% with
      celecoxib (P =.02 compared with the placebo group of the meta-analysis). The
      available data raise a cautionary flag about the risk of cardiovascular events
      with COX-2 inhibitors. Further prospective trial evaluation may characterize and
      determine the magnitude of the risk.

PMID- 11509061
TI  - A 47-year-old woman with tension-type headaches.

PMID- 11509062
TI  - Is pancreatic cancer a preventable disease?

PMID- 11509063
TI  - Diabetes mellitus--a call for papers.

PMID- 11509069
TI  - Use of prolonged standing for individuals with spinal cord injuries.
AB  - BACKGROUND AND PURPOSE: Prolonged standing in people with spinal cord injuries
      (SCIs) has the potential to affect a number of health-related areas such as
      reflex activity, joint range of motion, or well-being. The purpose of this study
      was to document the patterns of use of prolonged standing and their perceived
      effects in subjects with SCIs. SUBJECTS: The subjects were 152 adults with SCIs
      (103 male, 49 female; mean age=34 years, SD=8, range=18-55) who returned mailed
      survey questionnaires. METHODS: A 17-item self-report survey questionnaire was
      sent to the 463 members of a provincial spinal cord support organization.
      RESULTS: Survey responses for 26 of the 152 respondents were eliminated from the
      analysis because they had minimal effects from their injuries and did not need
      prolonged standing as an extra activity. Of the 126 remaining respondents, 38
      respondents (30%) reported that they engaged in prolonged standing for an average
      of 40 minutes per session, 3 to 4 times a week, as a method to improve or
      maintain their health. The perceived benefits included improvements in several
      health-related areas such as well-being, circulation, skin integrity, reflex
      activity, bowel and bladder function, digestion, sleep, pain, and fatigue. The
      most common reason that prevented the respondents from standing was the cost of
      equipment to enable standing. DISCUSSION AND CONCLUSION: Considering the many
      reported benefits of standing, this activity may be useful for people with SCI.
      This study identified a number of body systems and functions that may need to be
      investigated if clinical trials of prolonged standing in people with SCI are
      undertaken.

PMID- 11509070
TI  - Spinal movement and performance of a standing reach task in participants with and
      without Parkinson disease.
AB  - BACKGROUND AND PURPOSE: Evidence suggests that individuals with early and mid
      stage Parkinson disease (PD) have diminished range of motion (ROM). Spinal ROM
      influences the ability to function. In this investigation, the authors examined
      available spinal ROM, segmental excursions (the ROM used) during reaching, and
      their relationships in community-dwelling adults with and without PD. SUBJECTS:
      The subjects were 16 volunteers with PD (modified Hoehn and Yahr stages 1.5-3)
      and 32 participants without PD who were matched for age, body mass index, and
      sex. METHODS: Range of motion of the extremities was measured using a goniometer,
      and ROM of the spine was measured using the functional axial rotation (FAR) test,
      a measure of unrestricted cervico-thoracic-lumbar rotation in the seated
      position. Motion during reaching was determined using 3-dimensional motion
      analysis. Group differences were determined using multivariable analysis of
      variance followed by analysis of variance. Contributions to total reaching
      distance of segmental excursions (eg, thoracic rotation, thoracic lateral
      flexion) were determined using forward stepwise regression. RESULTS: Subjects
      with PD as compared with subjects without PD had less ROM (FAR of 98.2 degrees
      versus 110.3 degrees, shoulder flexion of 151.9 degrees versus 160.1 degrees) and
      less forward reaching (29.5 cm versus 34.0 cm). Lateral trunk flexion and total
      rotation relative to the ground contributed to reaching, with the regression
      model explaining 36% of the variance. DISCUSSION AND CONCLUSION: These results
      contribute to the growing body of evidence demonstrating that spinal ROM is
      impaired early in PD.

PMID- 11509071
TI  - Relationship of therapists' attitudes, children's motor ability, and parenting
      stress to mothers' perceptions of therapists' behaviors during early
      intervention.
AB  - BACKGROUND AND PURPOSE: Federal law mandates family-centered care as the service
      delivery model in early intervention programs for children from birth to 36
      months of age. This study investigated the relationship of therapists' attitudes,
      children's motor ability, and parenting stress to mothers' perceptions of
      physical therapists' family-centered behaviors during early intervention.
      SUBJECTS AND METHODS: Twenty-five physical therapists and 75 mother-child dyads
      (3 from each therapist's caseload) participated. The mean chronological age for
      the children was 21.2 months (SD=7.3, range=6-35). Mothers participated in a
      structured interview using the Measures of Processes of Care (MPOC-56), and they
      completed the Parenting Stress Index-Short Form (PSI-SF) and a questionnaire. The
      Bayley-II Motor Scale was administered to the children. Therapists completed a
      modified version of the Measures of Processes of Care for Service Providers (MPOC
      SP) and a questionnaire. RESULTS: Scores for mothers on the MPOC-56 and for
      therapists on the MPOC-SP indicated strong positive perceptions and attitudes
      toward family-centered behaviors. Hierarchical multiple regression analyses
      indicated that parenting stress explained a considerable amount of the variance
      in mothers' perceptions of family-centered behaviors, whereas therapists'
      attitudes explained a considerable amount of the variance in mothers' perceptions
      of respectful and supportive care. Children's motor ability was inversely related
      to parenting stress. DISCUSSION AND CONCLUSION: Findings suggest that mothers
      perceive that physical therapists are using family-centered behaviors in early
      intervention. Findings from the questionnaires suggest that some early
      intervention policies may be barriers for therapists and prevent them from
      actualizing attitudes toward family-centered behaviors.

PMID- 11509072
TI  - Variation by diagnostic and practice pattern groups in the mobility outcomes of
      inpatient rehabilitation programs for children and youth.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to describe variation in
      functional mobility outcomes among children and youth with different diagnoses
      and belonging to groups with different practice patterns from an inpatient
      pediatric rehabilitation hospital setting. SUBJECTS: A sample of 138 individuals
      between the ages of 1 and 22 years (mean=9.4, SD=5.3) was enrolled. METHODS:
      Physical therapists administered the "Mobility" domain of the Pediatric
      Evaluation of Disability Inventory at the time of admission and at the time of
      discharge. Mobility level (combined admission and discharge scores) and amount of
      change between and within 4 diagnostic groups (traumatic brain injury, non
      traumatic brain injury, orthopedic, and neurological) and 5 neuromuscular and
      musculoskeletal practice pattern groups were calculated, and post hoc analyses
      were done for specific contrast comparisons. RESULTS: Mobility scores between
      admission and discharge for all subgroups were different. Practice pattern groups
      were useful for identifying variations in level of motor performance. Diagnostic
      groups best described differences in mobility change during inpatient
      rehabilitation. DISCUSSION AND CONCLUSION: The use of practice patterns as
      grouping categories may enhance our understanding of variation in clinical
      outcomes of children during inpatient rehabilitation.

PMID- 11509073
TI  - Material properties of Thera-Band Tubing.
AB  - BACKGROUND AND PURPOSE: Thera-Band Tubing has been used in rehabilitation to
      provide resistance for exercise and splinting. However, the forces required to
      stretch the tubing have not been thoroughly quantified. Therefore, the therapist
      cannot assess, with certainty, how much force is applied when using a given
      length and type of Thera-Band Tubing. The purpose of this study was to quantify
      the material properties of Thera-Band Tubing. METHODS: Force versus percentage of
      strain for all types of Thera-Band Tubing was measured during elongation in a
      mechanical testing machine. RESULTS: The material is very compliant and displays
      nonlinear behavior in the initial stretching phase and linear behavior after 50%
      elongation. DISCUSSION AND CONCLUSION: From the data obtained in this project,
      plots that can provide the therapist with information about the forces needed for
      exercises with Thera-Band Tubing were generated. These data should allow
      therapists to make better choices about which size of tubing to use for each
      patient.

PMID- 11509074
TI  - Considerations for planning and conducting clinic-based research in physical
      therapy.
AB  - There is growing demand to increase the volume of clinic-based research in
      physical therapy. Special considerations, unique to the planning and conduct of
      clinic-based research, need to be addressed to increase the likelihood that these
      studies will be completed successfully. The purposes of this perspective are to
      discuss factors affecting clinic-based research and to offer suggestions for
      addressing these problems when designing and conducting research studies in a
      clinical setting. This perspective discusses issues such as patient management,
      determining the availability of target patient populations, acquiring support
      from physical therapists and physicians, reporting and managing research-related
      injury or illness, and modifying or terminating projects. Some of the points made
      in this perspective are illustrated using examples from the authors' experiences
      in conducting clinical research.

PMID- 11509075
TI  - Mental practice combined with physical practice for upper-limb motor deficit in
      subacute stroke.
AB  - BACKGROUND AND PURPOSE: This case report describes a patient with upper-limb
      hemiparesis (ULH) who received a program combining physical therapy for the
      affected side with mental practice. CASE DESCRIPTION: The patient was a 56-year
      old man with stable motor deficits, including ULH, on his dominant side resulting
      from a right parietal infarct that occurred 5 months previously. He received
      physical therapy for an hour 3 times a week for 6 weeks. In addition, 2 times a
      week the patient listened to an audiotape instructing him to imagine himself
      functionally using the affected limb. The patient also listened to the audiotape
      at home 2 times a week. Pretreatment and posttreatment measures were the upper
      extremity scale of the Fugl-Meyer Assessment of Sensorimotor Impairment (Fugl
      Meyer Scale), the Action Research Arm Test (ARA), and the Stroke Rehabilitation
      Assessment of Movement (STREAM). OUTCOMES: The patient exhibited reduction in
      impairment (Fugl-Meyer Scale) and improvement in arm function, as measured by the
      ARA and STREAM. DISCUSSION: Mental practice may complement physical therapy to
      improve motor function after stroke.

PMID- 11509076
TI  - Primary stroke prevention.
AB  - Stroke is one of the leading causes of death and disability worldwide. Although
      important advances in therapeutic approaches have been made, treatment is still
      far from satisfactory. Thus, major efforts should be made on stroke prevention.
      We present evidence-based recommendations for primary stroke prevention. Changes
      to modifiable risk factors, the role of drugs and surgery are discussed. New
      markers may help identification of subjects at high risk.

PMID- 11509077
TI  - The future of magnetic resonance-based techniques in neurology.
AB  - Magnetic resonance techniques have become increasingly important in neurology for
      defining: 1. brain, spinal cord and peripheral nerve or muscle structure; 2.
      pathological changes in tissue structures and properties; and 3. dynamic patterns
      of functional activation of the brain. New applications have been driven in part
      by advances in hardware, particularly improvements in magnet and gradient coil
      design. New imaging strategies allow novel approaches to contrast with, for
      example, diffusion imaging, magnetization transfer imaging, perfusion imaging and
      functional magnetic resonance imaging. In parallel with developments in hardware
      and image acquisition have been new approaches to image analysis. These have
      allowed quantitative descriptions of the image changes to be used for a precise,
      non-invasive definition of pathology. With the increasing capabilities and
      specificity of magnetic resonance techniques it is becoming more important that
      the neurologist is intimately involved in both the selection of magnetic
      resonance studies for patients and their interpretation. There is a need for
      considerably improved access to magnetic resonance technology, particularly in
      the acute or intensive care ward and in the neurosurgical theatre. This report
      illustrates several key developments. The task force concludes that magnetic
      resonance imaging is a major clinical tool of growing significance and offers
      recommendations for maximizing the potential future for magnetic resonance
      techniques in neurology.

PMID- 11509078
TI  - Costs, quality of life and disease severity in multiple sclerosis: a cross
      sectional study in Sweden.
AB  - This study assessed the cost to society of multiple sclerosis (MS) in Sweden in
      1998. The cost-of-illness method, based on the human capital theory, was used as
      the theoretical framework. The study used a cross-sectional approach, in which
      resource utilization data and quality-of-life data (utilities) were collected at
      a single time point. The total cost of MS was estimated at 4868 MSEK, or 586
      MEUR, giving an annual cost of 442 500 SEK, or 53 250 EUR, per patient (1USD =
      9.73 SEK, 1 EUR = 8.31 SEK, as of 21 September 2000). Direct costs accounted for
      about 67% of total cost, and they were dominated by the cost of personal
      assistants and drugs. Indirect costs (loss of production) accounted for about 33%
      of total costs. To these economic costs, intangible costs of 2702 MSEK (325 MEUR)
      should be added as well. Direct, indirect and informal care costs all rose
      significantly with increased disability and were higher during a relapse. Quality
      of life declined substantially with increased disability and was lower during a
      relapse. Multiple sclerosis was found to be associated with much higher costs to
      society than has been ascertained by former studies. The study also revealed a
      strong correlation between severity of the disease and quality of life. These
      results are crucial for further studies on the cost-effectiveness of new
      treatments aimed at preventing relapses and reducing progression of the disease.

PMID- 11509079
TI  - T1 lesion load and cerebral atrophy as a marker for clinical progression in
      patients with multiple sclerosis. A prospective 18 months follow-up study.
AB  - We investigated the relationship between local tissue destruction, diffuse
      cerebral atrophy and clinical progression in patients with established multiple
      sclerosis (MS). Twenty-nine patients with MS (13 patients with relapsing-
      remitting and 16 with secondary progressive disease) were included in a
      prospective serial study. Cerebral volumes, T1 hypointense lesion volumes, T2
      hyperintense lesion volumes at baseline and at 18 months follow-up, and the
      volume of monthly enhancing lesions from month 0 to month 9 were assessed on
      magnetic resonance imaging (MRI) brain scans using highly reproducible semi
      automated quantitative techniques. The main outcome measures were the MRI
      parameters and disability on Kurtzkes' Expanded Disability Status Scale. There
      was a significant correlation between the change (increase) in T1 lesion volume
      and progressive cerebral atrophy, whereas no correlation between the T2 lesion
      volume and atrophy was seen over the same follow-up period. The change in T1
      lesion volume correlated more strongly than did T2 lesion volume change with the
      change in disability. We conclude that hypointense abnormalities detected in T1
      weighted brain scans and cerebral atrophy may be directly linked. Although one
      should bear in mind some potential for reversibility due to inflammatory,
      oedematous lesions, these MR measures are a useful marker of progressive tissue
      damage and clinical progression in established MS.

PMID- 11509080
TI  - Malondialdehyde, glutathione peroxidase and superoxide dismutase in peripheral
      blood erythrocytes of patients with acute cerebral ischemia.
AB  - The levels of malondialdehyde (MDA), glutathione peroxidase (GSH-Px) and
      superoxide dismutase (SOD-1) were measured in the red blood cells (RBC) of 34
      patients with acute ischemic hemispheric stroke on the first and seventh day
      after their stroke onset, and compared with 30 control individuals matched for
      sex, age and stroke risk factors. Within the first 24 h after stroke, SOD and GSH
      Px activities were significantly decreased and MDA levels were significantly
      elevated in the patients compared with control subjects. Decrease in SOD and GSH
      Px activities and increase in MDA levels showed significant correlation with
      infarct size, initial stroke severity assessed by NIH stroke scale and poor short
      term prognosis. Observed changes in the RBC oxygen scavenging process returned to
      values not different from those of control subjects within seven days after
      stroke. Our results indicated that antioxidant enzyme concentrations decreased
      below normal levels in the acute period following ischemic stroke. Until the
      recovery of antioxidant defence mechanisms, which occurred up to seven days after
      stroke onset according to our results, the use of neuroprotective therapy against
      oxyradical injury seems reliable.

PMID- 11509081
TI  - Twelve-month safety of entacapone in patients with Parkinson's disease.
AB  - The safety of entacapone combined with levodopa and a dopadecarboxylase (DDC)
      inhibitor was tested in a 12-month double-blind study of 326 patients with
      idiopathic Parkinson's disease (PD). The study population represented 'typical'
      PD outpatients, including patients with varying disease severity and with various
      concomitant medications. Two-thirds of the patients were randomized to receive
      200 mg of entacapone with each of 2--10 daily levodopa doses, and one-third to
      receive placebo. All entacapone patients were included in the safety evaluation
      of adverse events (AEs), vital signs, ECG, and laboratory parameters. Entacapone
      was well tolerated with a discontinuation rate due to AEs of 14% compared with
      11% with placebo (NS). As expected, due to dopaminergic enhancement, dyskinesia
      was more frequent as an AE with entacapone than with placebo. Dryness of mouth,
      urine discoloration and diarrhoea were more frequent non-dopaminergic AEs with
      entacapone than with placebo. Entacapone had no adverse effects on hepatic enzyme
      activity, ECG or haemodynamic parameters, and there was no evidence of any
      toxicity. As an indication of levodopa enhancement with entacapone, patients
      taking 5--10 doses of levodopa, most likely representing predominantly
      fluctuating patients, showed a significant decrease in their mean daily levodopa
      dose of 94 mg in the entacapone group compared with a decrease of 39 mg in the
      placebo group (P < 0.01). The interval between the first two morning doses of
      levodopa increased by 17% with entacapone, whereas with placebo no extension was
      observed (P < 0.05). Despite levodopa dose reduction, efficacy of entacapone was
      maintained. As further evidence of efficacy, Parkinsonian symptoms markedly
      worsened in all patients after withdrawal of entacapone. We conclude that
      entacapone is safe in optimizing levodopa in long-term treatment of idiopathic
      Parkinson's disease. Monitoring of liver or other safety parameters during
      entacapone treatment is not required.

PMID- 11509082
TI  - Validation of a migraine-specific questionnaire for use in family studies.
AB  - The availability of valid migraine-specific questionnaires is important when
      large numbers of migraine patients have to be analysed. The Finnish Migraine
      Specific Questionnaire has been validated in two stages. In the first, a clinical
      diagnosis of migraine was reached, using International Headache Society criteria,
      in 100 consecutive patients. Migraine was then diagnosed independently on the
      basis of responses to the Finnish Migraine-Specific Questionnaire. In the second
      stage, responses to 100 questionnaires returned consecutively in a family study
      in progress were analysed, and respondents were contacted by telephone for
      interview and diagnosis of migraine. Contact proved impossible in six cases. The
      sensitivity of the questionnaire for migraine was 0.99 (167 out of 168;
      validation stages 1 and 2 combined) and specificity was 0.96 (25 out of 26 cases;
      validation stage 2). It also proved possible to differentiate between migraine
      with and without aura on the basis of responses to the Finnish Migraine-Specific
      Questionnaire: chance-corrected agreement (Cohen's kappa) was 0.804 in relation
      to diagnoses reached on the basis of responses to the Finnish Migraine-Specific
      Questionnaire and clinically was 0.858 in relation to diagnoses reached on the
      basis of responses to the Finnish Migraine-Specific Questionnaire combined with
      the results of the telephone interviews. A value for Cohen's kappa > 0.75
      indicates good agreement. Therefore, use of the Finnish Migraine-Specific
      Questionnaire in research into migraine genetics is justified.

PMID- 11509083
TI  - Atypical neurological involvement associated with celiac disease.
AB  - We report an unusual case of celiac disease in a 31-year-old woman with gait
      disorder, stimulus-induced myoclonus and abnormalities of eye movement. We
      suggest that celiac disease can present with a variety of unusual neurological
      manifestations.

PMID- 11509084
TI  - Gabapentin in painful HIV-related neuropathy: a report of 19 patients,
      preliminary observations.
AB  - The objective of this study was to assess the efficacy and safety of Gabapentin
      as the sole analgesic in patients with HIV-related painful neuropathy. Nineteen
      patients with HIV-related painful neuropathy were administered Gabapentin.
      Efficacy was evaluated with two 100-mm Visual Analogue Scales (VAS) (0: no
      symptom; 100: worst symptom), rating pain and interference of pain with sleep,
      performed at baseline and monthly intervals. Main Pain VAS score decreased from a
      baseline of 55.7 +/- 19.1 mm to a final 14.7 +/- 18.6 mm (ANOVA P = 0.0001) and
      mean Sleep Interference VAS score decreased from a baseline of 60.4 +/- 31.9 mm
      to a final 15.5 +/- 27.7 mm (ANOVA P = 0.0001). Gabapentin provided significant
      pain relief in our patients with HIV-associated painful sensory neuropathy.

PMID- 11509085
TI  - Central and peripheral nervous system complications following allogeneic bone
      marrow transplantation.
AB  - Although graft vs. host disease (GvHD) is a frequent complication of allogeneic
      bone marrow transplantation (BMT), involvement of the central and peripheral
      nervous systems (CNS and PNS, respectively) has not been demonstrated
      conclusively. Here, we report of a patient who, following allogeneic BMT for
      lymphoblastic T-cell lymphoma, suffered a syndrome characterized by self
      remitting cerebellar and pyramidal signs associated with a progressive
      involvement of the peripheral nervous system (PNS). Clinical course and
      laboratory findings correlated with relapses of systemic GvDH, thus suggesting
      the possibility that involvement of CNS and PNS may be sustained by a similar
      pathogenic mechanism.

PMID- 11509086
TI  - Vinpocetine treatment in acute ischaemic stroke: a pilot single-blind randomized
      clinical trial.
AB  - The aim of the study was to assess the safety and feasibility of a clinical trial
      on the effect of vinpocetine, a synthetic ethyl ester of apovincamine, in acute
      ischaemic stroke. Thirty consecutive patients with computed tomography verified
      diagnosis of acute ischaemic stroke, who could receive drug treatment within 72 h
      of stroke onset, were enrolled. The patients were randomly allocated to receive
      either low-molecular weight dextran alone or in combination with vinpocetine.
      Poor outcome was defined as being dead or having a Barthel index of < 70 or a
      Rankin score of 3--5. Intention-to-treat analysis was applied. One-tenth of all
      hospitalized patients with acute ischaemic stroke were eligible for the trial.
      Thirty eligible patients were treated with either low-molecular weight dextran
      alone (mean age 57.9 +/- 11.6 years, n = 15) or in combination with vinpocetine
      (mean age 60.8 +/- 6.6 years, n = 15). The two treatment groups were comparable
      with respect to major prognostic variables. A relative risk (RR) reduction of
      poor outcome at 3 months follow-up was 30% (RR = 0.7; 95% confidence interval
      [CI] 0.1--3.4), as defined by the modified Barthel Index, and 60% as defined by
      the modified Ranking score (RR = 0.4, 95% CI: 0.1--1.7). The National Institute
      of Health (NIH--NINDS) Stroke Scale score was marginally significantly better in
      the vinpocetine treated group at 3 months of follow-up (P = 0.05, ANOVA). No
      significant adverse effects were seen. This pilot study shows that a full-scale
      randomized double-blind, placebo-controlled trial of vinpocetine treatment in
      acute ischaemic stroke is feasible and warranted.

PMID- 11509087
TI  - Is isolated vitamin B12 deficiency a sufficient causative factor of dementia?

PMID- 11509088
TI  - Fibromuscular dysplasia of the basilar artery: a case presenting with
      vertebrobasilar TIAs.

PMID- 11509089
TI  - Writing and praxis: what is new?

PMID- 11509090
TI  - The clinical involvement patterns of neuro-Behcet's disease.

PMID- 11509091
TI  - Headache in dementia.

PMID- 11509092
TI  - Micronutrients: oxidant/antioxidant status.
AB  - Potentially damaging species (reactive oxygen, nitrogen and chlorine species)
      arise as by-products of metabolism and as physiological mediators and signalling
      molecules. Levels of these species are controlled by the antioxidant defence
      system. Several components of this system are micronutrients (e.g. vitamins C and
      E) or are dependent upon dietary micronutrients (e.g. CuZn and Mn superoxide
      dismutase). The antioxidant defences act as a coordinated system where
      deficiencies in one component may affect the efficiency of the others. Oxidative
      stress may be an important factor in infection if micronutrients are deficient.

PMID- 11509093
TI  - Immunobiology of mild micronutrient deficiencies.
AB  - Nutrition is a critical determinant of the outcome of host microbe interactions
      through a modulation of the immune response. Besides macronutrient malnutrition,
      deficiencies of several macronutrients also influence immune homeostasis and thus
      affect infection-related morbidity and mortality. Deficiencies of micronutrients
      like vitamin A, iron and zinc are widely prevalent among populations living in
      developing countries. Besides their severe deficiencies, subclinical deficiencies
      are known to impair biological functions in the host, immune function being one
      of them. The effects of these micronutrients on various immune mechanisms are
      briefly reviewed in this article.

PMID- 11509094
TI  - Immunobiology of gestational zinc deficiency.
AB  - The trace element zinc is an essential micronutrient for the proper functioning
      of the immune system. Zinc deficiency leads to impaired function of the
      unspecific and specific immune response and consequently to an increased
      susceptibility to bacterial, viral and fungal infections. Immunological defects
      are not only seen in pronounced but even in marginal and moderate zinc
      deficiency. Lack of zinc is especially harmful for the development of the immune
      system, which stresses the importance of a balanced zinc level during pregnancy.
      However, gestational zinc deficiency due to an imbalance between intake and
      increased requirements is a common problem world-wide. In animals, gestational
      zinc deficiency results in reduced thymic and spleen size and depressed active
      and passive immunity in the infant. For example, depressed immunoglobulin levels,
      altered antibody repertoire, reduced proliferative response of lymphocytes and
      diminished neutrophil functions have been reported. Interestingly, immune defects
      caused by prenatal zinc deficiency, such as depressed antibody levels and
      lymphocyte proliferation, may even persist in subsequent generations and are not
      reversible by postnatal zinc administration. Since gestational zinc deficiency is
      a common problem throughout all cultures and socioeconomic levels, it might have
      immense consequences for the health status of the population. Based on a summary
      of the immunobiology of zinc, this article reviews the significance of zinc
      deficiency during pregnancy and the effect of gestational zinc deficiency on
      passive and active immunity in the infant. It provides a rational basis for both
      immunological laboratory investigations and field studies, such as large
      community-based zinc supplementation trials in pregnant women.

PMID- 11509095
TI  - Prevalence of micronutrient deficiency particularly of iron, zinc and folic acid
      in pregnant women in South East Asia.
AB  - Micronutrient deficiency, whether clinical or subclinical, may affect growth,
      cognition and reproductive performance. In pregnant women moderate to severe
      deficiencies of iron, zinc and folic acid have been shown to increase risk of low
      birth weight, pregnancy complications and birth defects. Any attempt to introduce
      a micronutrient supplementation programme during pregnancy must be based on
      adequate data on the prevalence of micronutrient deficiencies, their adverse
      effects and the potential for reversing these through supplementation. This paper
      reviews parameters for assessment of iron, zinc and folic acid deficiencies in
      pregnancy and the available data on prevalence of these in pregnant women in
      South Asia. Iron deficiency and anemia affect 50 % or more of pregnant women, the
      prevalence of folic acid deficiency may be up to 30-50 % and there is evidence to
      suggest that zinc deficiency is likely to be widespread but supportive data are
      scarce.

PMID- 11509096
TI  - Nutrition and maternal morbidity and mortality.
AB  - Nearly 600 000 women die every year from pregnancy related conditions and the
      maternal mortality rates (MMR = deaths per 100 000 live births) in developing
      countries may be as high as 1000 compared with less than ten in industrialised
      countries. In the light of the striking impact of deficiencies of micronutrients
      such as vitamin A and zinc on immune function, morbidity and mortality in
      children it seems reasonable to suggest that such deficiencies might play a
      contributing role in the high rates of morbidity and mortality in mothers.
      Hitherto, there has been rather little published on the contribution of
      malnutrition to maternal morbidity or mortality but recent results of
      micronutrient supplementation show a major effect of vitamin A or beta carotene
      supplementation on maternal mortality in Nepal and an impressive effect of a
      multiple micronutrient mixture on pregnancy outcome in Tanzania. There is now
      data showing that subclinical mastitis, a potential risk factor for mother to
      child transmission of HIV by increasing levels of virus in breast milk, is
      influenced by maternal diet in Tanzania and feeding patterns in South Africa.
      Considering the massive tragedy of maternal mortality the recent data provides
      opportunities for new, innovative nutritional interventions for the reduction of
      the global burden of maternal morbidity and mortality.

PMID- 11509097
TI  - Effect of gestational zinc deficiency on pregnancy outcomes: summary of
      observation studies and zinc supplementation trials.
AB  - The lack of a valid indicator precludes a true estimate of zinc deficiency in
      pregnancy in various populations. However, it is possible that mild to moderate
      deficiency (as assessed by available indicators) may be common in the developing
      world. Animal experiments indicate that zinc deficiency can result in adverse
      maternal and fetal consequences. Human data, particularly from prenatal zinc
      supplementation trials, has failed to document a consistent maternal or infant
      benefit on evaluated outcome measures including pregnancy induced hypertension,
      preterm/post-term labour, premature rupture of membranes, maternal infection,
      postpartum haemorrhage, perinatal mortality, congenital malformations and fetal
      growth and gestation. Preliminary data suggest a beneficial effect of prenatal
      zinc supplementation on infants' neurobehavioural development and immune function
      (evaluated by diarrhoeal and ARI morbidity incidence in the first year of life).
      Future research should focus on these functional consequences and congenital
      malformations (with adequate sample sizes), and simultaneously address the safety
      issue, particularly in relation to micronutrient interactions. In the light of
      the currently available information, routine zinc supplementation can not be
      advocated to improve pregnancy outcome.

PMID- 11509098
TI  - Folate, vitamin B12 and homocysteine in relation to birth defects and pregnancy
      outcome.
AB  - Increased folate intake reduces the risk of neural tube defects, other
      malformations and also possibly, pregnancy complications. Increasing evidence
      suggests that the beneficial effect of folate may be related to improved function
      of methionine synthase, a vitamin B12-dependent enzyme that converts homocysteine
      to methionine. In India, the majority of the population adheres to a vegetarian
      diet known to be deficient in vitamin B12. In such a population, increased folate
      intake may offer minimal protection against birth defects, whereas vitamin B12
      administration should be considered. In this review, is described the metabolism
      of and interrelations between folate, vitamin B12 and homocysteine. This is
      followed by a brief discussion of some of the proposed mechanisms for their
      biological effects in relation to birth defects and pregnancy outcome.

PMID- 11509099
TI  - Importance of folate in human nutrition.
AB  - From a public health perspective, some of the new insights into folic acid
      nutrition are of significance. Folate intake recommendations vary under different
      conditions. Intake of 350 microg is required to maintain plasma homocysteine
      levels, 650 microg for those with elevated plasma homocysteine, about 400 microg
      for women planning to become pregnant and 4000 microg for those with history of
      neural tube defect affected pregnancy. This raises the question whether the
      folate intake is adequate for the general population, particularly in the
      vulnerable groups or whether there is a need for scientists to take a fresh view
      of the requirements, recommended dietary intakes, and consider intervention
      measures which will have impact on the folate nutritional status. The
      recommendations should provide a margin of safety to allow for decreased intake,
      increased requirements, individual variability and bioavailability of natural
      food folates. The folate intake and nutriture in relation to India and other
      developing countries needs careful consideration to reduce anemia, neural tube
      defects and possibly impact on the high incidence of cardiovascular diseases.

PMID- 11509100
TI  - Zinc and childhood infectious disease morbidity and mortality.
AB  - Zinc is an essential mineral and deficiency results in abnormal immune function
      and higher rates of infectious diseases. Randomized controlled trials of zinc
      supplementation have been conducted in children in developing countries to
      determine effects on infectious disease morbidity and mortality. Zinc
      supplemented children have been found to have lower rates of diarrhea, pneumonia
      and malaria in comparison with children not given zinc. Zinc used as an adjunct
      to fluid and dietary management of acute and persistent diarrhea has been found
      to reduce diarrheal duration and severity. Preliminary evidence suggests that
      zinc supplementation in children in poor developing country settings may also
      reduce infant mortality, but larger trials are needed to address this important
      issue. Preventive and therapeutic interventions should be implemented in
      developing countries where zinc deficiency is likely to be prevalent.

PMID- 11509101
TI  - Effect of micronutrient supplementation on linear growth of children.
AB  - This review summarizes the results of published, randomized clinical trials that
      have examined the impact of administration of micronutrients, singly or in
      combination to infants, preschool and school children on linear growth.
      Supplementation of single micronutrients resulted in small or no benefits on
      linear growth. A meta-analysis of zinc supplementation trials confirmed that zinc
      has a significant but small impact (0.22 sd units) on length gain in children 0
      13 years of age. However, a recent study reported a substantially greater benefit
      (>1 sd) in stunted and non-stunted breast-fed infants 6-12 months of age. With
      iron supplementation, a beneficial effect was found only in anemic children.
      Vitamin A supplementation trials have reported little or no benefit on linear
      growth. Data currently available suggest some impact in children with clinical or
      biochemical vitamin A deficiency, but this issue needs confirmation. Few studies
      could be identified where a combination of micronutrients was given as a
      supplement or as fortified food; in the latter set of studies energy availability
      was assured. The impact on length without multiple micronutrient supplementation
      was no greater than that observed with single micronutrients. In conclusion, zinc
      and iron seem to have a modest effect on linear growth in deficient populations.
      Vitamin A is unlikely to have an important effect on linear growth. Limited
      available evidence does not allow us to conclude whether a combination of
      micronutrients, with or without additional food, would have a greater impact than
      that seen with zinc alone.

PMID- 11509102
TI  - Zinc and cognitive development.
AB  - Cognition is a field of thought processes by which an individual processes
      information through skills of perception, thinking, memory, learning and
      attention. Zinc deficiency may affect cognitive development by alterations in
      attention, activity, neuropsychological behavior and motor development. The exact
      mechanisms are not clear but it appears that zinc is essential for neurogenesis,
      neuronal migration, synaptogenesis and its deficiency could interfere with
      neurotransmission and subsequent neuropsychological behavior. Studies in animals
      show that zinc deficiency during the time of rapid brain growth, or during the
      juvenile and adolescent period affects cognitive development by decreasing
      activity, increasing emotional behavior, impairing memory and the capacity to
      learn. Evidence from human studies is limited. Low maternal intakes of zinc
      during pregnancy and lactation were found to be associated with less focused
      attention in neonates and decreased motor functions at 6 months of age. Zinc
      supplementation resulted in better motor development and more playfulness in low
      birth weight infants and increased vigorous and functional activity in infants
      and toddlers. In older school going children the data is controversial but there
      is some evidence of improved neuropsychological functions with zinc
      supplementation. Additional research is required to determine the exact
      biological mechanisms, the critical periods, the threshold of severity and the
      long-term effects of zinc deprivation on cognitive development.

PMID- 11509103
TI  - Iron and the brain: neurotransmitter receptors and magnetic resonance
      spectroscopy.
AB  - Earlier studies show that in iron deficiency with anaemia and in latent iron
      deficiency neurotransmitters are altered. The changes induced in the fetal brain
      are irreversible on rehabilitation. The important alterations in glutamate
      metabolism in latent iron deficiency stimulated studies on gamma aminobutyric
      acid and glutaminate receptors. It was observed that binding of 3H-muscimol at pH
      7.5 and 1 mg protein/assay increased significantly in synaptic vesicular
      membranes and under similar conditions 3H-glutamate binding showed reduction.
      Thus iron deficiency played a role in both excitatory and inhibitory
      neurotransmitter receptors. To elucidate the role of body iron status on the
      brain, anaemic children with thalassemia and iron deficiency were subjected to
      'magnetic resonance spectroscopy' of globus pallidus, caudate and dentate nuclei
      and there was no change in iron content. The concentrations of creatinine and
      aspartate increased, with lowering of choline content. The findings were similar
      in thalassemia as well as iron deficiency anaemia, suggesting that in anaemia
      changes operate through reduced oxygen availability.

PMID- 11509104
TI  - Micronutrients as adjunct therapy of acute illness in children: impact on the
      episode outcome and policy implications of current findings.
AB  - Role of micronutrients namely vitamin A, zinc and folate, as adjunct therapy of
      illness episodes in children in developing countries have been discussed in the
      light of health policy. Apart from a selective review, attempts have been made to
      statistically combine results of several studies to address policy issues. In
      children, vitamin A supplementation during illness has (a) a profound effect in
      reducing mortality in measles, (b) possibly a significant effect in reducing
      persistent diarrhea episodes in children with acute diarrhea, and (c) no benefit
      in pneumonia. Use of large dose vitamin A is recommended during measles episodes
      but not in non-measles pneumonia. Its use in acute diarrhea is debatable but
      recommended in persistent diarrhea and in severe malnutrition as a component of a
      micronutrient mixture. Large dose vitamin A supplementation should be used with
      caution in young infants as there are unresolved concerns about its safety
      particularly, bulging fontanelle observed in infants when co-administered at
      immunization. In children, zinc supplementation during illness, (a) had a marked
      effect in reducing prolonged episodes and a modest effect on episode duration in
      acute diarrhea, (b) resulted in reduced rate of treatment failure and death in
      persistent diarrhea, (c) had no effect in measles and non-measles pneumonia, and
      (d) probably had a detrimental effect of increasing death rate when a large dose
      was used in severely malnourished children. The desirability of routine zinc
      supplementation therapy of undernourished children with acute diarrhea should be
      assessed further. Concerning policy, zinc supplementation as a component of a
      micronutrient mixture is recommended in the rehabilitation of severely
      malnourished children and in persistent diarrhea. However, recommendation for its
      routine use in all cases of acute diarrhea in children needs additional studies
      on effectiveness, cost, operations and safety. In two randomized controlled
      trials folate has been evaluated in acute and persistent diarrhea and found to
      have no beneficial effect. Folate is not recommended as adjunct therapy of
      diarrhea. Role of folate in preventing severe disease and/or death deserves
      further evaluation.

PMID- 11509105
TI  - Dietary diversification/modification strategies to enhance micronutrient content
      and bioavailability of diets in developing countries.
AB  - Both cereal staples and household diets can be manipulated to enhance the content
      of micronutrients and/or alter the levels of absorption modifiers to improve
      micronutrient bioavailability. Strategies described range from plant breeding,
      use of fertilizers and genetic engineering to changes in food preparation and
      processing methods at the household level involving soaking, fermentation and
      germination. The impact of five household strategies designed to enhance the
      content and bioavailability of iron, zinc and calcium in a representative daily
      menu for rural Malawian preschool children has been calculated using food
      composition data. In the five strategies, relishes based on small dried fish
      replaced plant-based relishes, maize-based porridges prepared with maize flour
      soaked to reduce its hexa (IP-6)- and penta (IP-5)-inositol phosphate content
      replaced conventional porridges; and a pumpkin-leaf relish replaced sweet potato
      to increase the retinol content of the daily menu. Comparison of the calculated
      energy, nutrient, and phytate content, and [phytate]:[zinc] molar ratios of the
      five modified menus compared with the unmodified menu emphasizes that to ensure
      that the estimated requirements for iron and zinc are met, the optimal strategy
      includes dried fish relish twice daily together with porridges prepared using
      soaked (or fermented) maize flour to reduce their hexa- and penta-inositol
      phosphate content. Implementation of these household strategies has the potential
      to increase the bioavailability of iron and zinc in rural Malawian diets from low
      to high.

PMID- 11509106
TI  - Prospects of fortification of salt with iron and iodine.
AB  - Fortification of salt with iron has been developed by the National Institute of
      Nutrition (NIN) as a strategy for the control of iron deficiency anaemia (IDA) in
      India, similar to iodization of salt for control of iodine deficiency disorders
      (IDD). Stability of the iron fortified salt (IFS), its bioavailability and
      organoleptic evaluation of food items containing the IFS have been demonstrated.
      Acceptability and effectiveness of the IFS in school children and in multicentric
      community trials have been demonstrated. With the introduction of universal
      iodization of salt as a national policy in 1988, NIN has developed a formulation
      for double fortification (DFS) of salt with iodine and iron. The stability of the
      nutrients under laboratory conditions along with their bioavailability were found
      to be good but varying with the quality of salt used. The DFS has been evaluated
      in controlled trials in tribal communities and in residential school children.
      The findings of these studies are discussed. Overall, in these trials, DFS
      effectively controlled iodine deficiency but a clear impact on reducing anaemia
      was not demonstrated. In residential schoolchildren, increased urinary excretion
      of iodine as well as reduced anaemia were observed. The quality of salt has been
      found to be an important determinant of the stability of iodine in DFS. Further
      evaluation of this potentially important intervention is in progress.

PMID- 11509107
TI  - Highly nutrient-dense spreads: a new approach to delivering multiple
      micronutrients to high-risk groups.
AB  - Using a highly fortified food is the most attractive option to bringing missing
      nutrients to vulnerable groups. The recent development of a highly nutrient-dense
      spread (HNDS) for the treatment of malnourished children may have some relevance
      for other high-risk groups. Traditionally, severely malnourished children are fed
      for 3-4 weeks during their recovery with adapted milk feeds prepared by mixing
      dried skimmed milk, oil and sugar with a vitamin and mineral complex. This
      approach, however, is difficult to implement, since these feeds are excellent
      growth media for bacteria, and they must be prepared and fed under close
      supervision. This constraint led to the development of a HNDS, which is obtained
      by replacing part of the dried skimmed milk with a mixture of groundnut butter
      and powdered lactoserum. This spread can be eaten without dilution with water and
      preliminary trials showed that children preferred this HNDS to traditional liquid
      diets. In HNDS all powdered ingredients are embedded in fat which protects
      vitamins against oxidation and increases the shelf life of this product. Spreads
      also have a very low humidity and bacteria do not grow in it. Attempts to use
      spreads to supplement other vulnerable groups such as moderately malnourished
      children and pregnant women are discussed.

PMID- 11509108
TI  - Micronutrient interactions: effects on absorption and bioavailability.
AB  - A potential risk of interactions between micronutrients affecting absorption and
      bioavailability has to be considered in any supplementation or fortification
      strategy. At levels of essential micronutrients present in foods, most
      micronutrients appear to utilise specific absorptive mechanisms and not be
      vulnerable to interactions. In aqueous solutions and at higher intake levels
      competition between elements with similar chemical characteristics and uptake by
      non-regulated processes can take place. These interactions have clearly been
      demonstrated in experimental absorption studies and to some extent have been
      confirmed in supplementation studies. Negative effects of iron supplementation on
      indices of zinc and copper status and of zinc supplementation on iron and copper
      status have been reported. In contrast, the negative effect of calcium on iron
      absorption has not been confirmed in long-term supplementation studies. Ascorbic
      acid has a strong iron absorption promoting potential and in iron deficient
      populations ascorbic acid supplementation improves iron status. Thus, ascorbic
      acid supplements or an increased intake of ascorbic acid rich foods could have
      important public health implications, especially in populations subsisting on a
      mainly plant food based diet. The effect of poor status of a given micronutrient
      on absorption and utilisation of other micronutrients should also be considered
      while developing strategies to improve micronutrient status in a population.
      Awareness of these interactions, combined with a balanced evaluation of the
      dietary intake of the population with regard to absorption promoting and
      inhibiting substances and the risk for multiple deficiencies, could lead to more
      effective strategies to improve micronutrient status.

PMID- 11509109
TI  - Alternate strategies for improving iron nutrition: lessons from recent research.
AB  - Strategies such as dietary diversification and food fortification have yielded
      significant results in controlling iron deficiency anaemia in developed
      countries. Reducing the prevalence of iron deficiency anaemia in developing
      countries is still a matter of importance. The major factors responsible for iron
      deficiency anaemia in the vulnerable segments of developing countries are reduced
      intake and poor bioavailability of dietary iron. Dietary diversification and food
      based approaches pose considerable challenges before they can be implemented on a
      wide scale. Anaemia control programmes based on the administration of
      prophylactic doses of iron and folic acid tablets have been widely implemented.
      As the programmes were not effective in countries such as India, the dosage of
      iron was increased. The role of excess iron in causing intestinal oxidative
      stress has drawn attention to other approaches of iron supplementation.
      Prophylactic administration of iron along with antioxidants like vitamins E and C
      or foods rich in these vitamins is one such strategy. To reduce the intestinal
      oxidative stress, intermittent supplementation of iron is being considered. The
      potential benefits and shortcomings of these approaches are reviewed.

PMID- 11509110
TI  - Micronutrients in pregnancy.
AB  - Vitamins and minerals, referred to collectively as micronutrients, have important
      influences on the health of pregnant women and the growing fetus. Iron deficiency
      results in anemia which may increase the risk of death from hemorrhage during
      delivery, but its effects on fetal development and birth outcomes is still
      unclear. Folic acid deficiency can lead to hematological consequences, pregnancy
      complications and congenital malformations, but again the association with other
      birth outcomes is equivocal. Zinc deficiency has been associated in some, but not
      all studies with complications of pregnancy and delivery, as well as with growth
      retardation, congenital abnormalities and retarded neurobehavioral and
      immunological development in the fetus. Iodine deficiency during pregnancy
      results in cretinism and possible fetal wastage and preterm delivery. Deficiency
      of other minerals such as magnesium, selenium, copper, and calcium have also been
      associated with complications of pregnancy, childbirth or fetal development.
      Deficiencies of vitamins other than folate may likewise be related to such
      complications; and vitamin A or beta-carotene supplements in pregnancy reduced
      maternal mortality by 50 % in a controlled trial in Nepal. Additional research is
      need on the prevalence of such deficiencies and their consequences and on cost
      effective public health interventions for their control.

PMID- 11509111
TI  - Micronutrient deficiency in children.
AB  - Malnutrition increases morbidity and mortality and affects physical growth and
      development, some of these effects resulting from specific micronutrient
      deficiencies. While public health efforts must be targeted to improve dietary
      intakes in children through breast feeding and appropriate complementary feeding,
      there is a need for additional measures to increase the intake of certain
      micronutrients. Food-based approaches are regarded as the long-term strategy for
      improving nutrition, but for certain micronutrients, supplementation, be it to
      the general population or to high risk groups or as an adjunct to treatment must
      also be considered. Our understanding of the prevalence and consequences of iron,
      vitamin A and iodine deficiency in children and pregnant women has advanced
      considerably while there is still a need to generate more knowledge pertaining to
      many other micronutrients, including zinc, selenium and many of the B-vitamins.
      For iron and vitamin A, the challenge is to improve the delivery to target
      populations. For disease prevention and growth promotion, the need to deliver
      safe but effective amounts of micronutrients such as zinc to children and women
      of fertile age can be determined only after data on deficiency prevalence becomes
      available and the studies on mortality reduction following supplementation are
      completed. Individual or multiple micronutrients must be used as an adjunct to
      treatment of common infectious diseases and malnutrition only if the gains are
      substantial and the safety window sufficiently wide. The available data for zinc
      are promising with regard to the prevention of diarrhea and pneumonia. It should
      be emphasized that there must be no displacement of important treatment such as
      ORS in acute diarrhea by adjunct therapy such as zinc. Credible policy making
      requires description of not only the clinical effects but also the underlying
      biological mechanisms. As findings of experimental studies are not always
      feasible to extrapolate to humans, the biology of deficiency as well as excess of
      micronutrients in humans must continue to be investigated with vigour.

PMID- 11509112
TI  - Decrease in risk of lung cancer death in males after smoking cessation by age at
      quitting: findings from the JACC study.
AB  - To evaluate the impact of smoking cessation in individuals and populations, we
      examined the decrease in risk of lung cancer death in male ex-smokers by age at
      quitting in the Japan Collaborative Cohort Study for Evaluation of Cancer Risk
      Sponsored by Monbusho (JACC Study), which was initiated from 1988 to 1990 in
      Japan. For simplicity, subjects were limited to male non-smokers, and former /
      current smokers who started smoking at ages 18 - 22, and 33654 men aged 40 - 79
      years were included. We modeled the mortality rates in non-smokers and current
      smokers, and compared the rates in ex-smokers with those expected from the model
      if they had continued smoking. During the mean follow-up of 8.0 years, 341 men
      died from lung cancer. The mortality rate ratio for current smokers, compared to
      non-smokers, was 5.16, and those for ex-smokers who had quit smoking 0 - 4, 5 -
      9, 10 - 14, 15 - 19 and > or = 20 years before were 4.84, 3.19, 2.03, 1.29 and
      0.99, respectively. The functions of 3.20 x 10(-7) x (age)(4.5) and 1.96 x 10(-5)
      x (age - 29.6)(4.5) fitted the observed mortality rates (per 100000 person-years)
      in non-smokers and continuing smokers, respectively. A greater decrease in lung
      cancer mortality was estimated among those who quit smoking at younger ages.
      Stopping smoking earlier in life appears preferable to keep the individual risk
      low. The absolute rate, however, substantially decreased after smoking cessation
      even in those who quit at ages 60 - 69, reflecting the high mortality rate among
      continuing smokers in the elderly.

PMID- 11509113
TI  - Serological Immunoglobulin G antibody titers to Helicobacter pylori in Japanese
      Brazilian and Non-Japanese Brazilian gastric cancer patients and controls in Sao
      Paulo.
AB  - Helicobacter pylori (H. pylori) infection is considered a cause of gastric cancer
      (GC), though evidence for this association is scarce in high-risk areas. Possible
      case control and/or ethnic differences were investigated as to the presence of H.
      pylori and its immunogloblin G antibody titer in the multi-ethnic city of Sao
      Paulo, where the incidence of GC is relatively high. We performed a cross
      sectional comparison of antibody titers to H. pylori in Japanese Brazilian, and
      non-Japanese Brazilian GC patients and their controls. Japanese Brazilian
      patients were matched by age, sex and ethnicity with two controls, while non
      Japanese Brazilian patients were matched as above with one control. Among
      Japanese Brazilians, 59 of 93 (63.4%) patients with GC and 127 of 186 (68.3%)
      controls were positive for H. pylori-specific antibody (odds ratio (OR) = 0.80,
      95% confidence interval (CI) = 0.47 - 1.36), while among non-Japanese Brazilians,
      171 of 228 patients with GC (75.7%) and 178 of 226 controls (78.8%) were positive
      (OR = 0.84, 95% CI = 0.54 - 1.30). The median serum antibody titer was lower in
      cases than in controls in both ethnic groups. A high titer (H. pylori titer > or
      = 50) was associated with less likelihood of GC for both ethnic groups (for
      Japanese Brazilians, OR = 0.39, 95% CI = 0.16 - 0.92; for non-Japanese
      Brazilians, OR = 0.56, 95% CI = 0.31 - 1.02). The high titer can be regarded as a
      sign of the necessity of eradication, and low titer is regarded as a sign of the
      necessity of close screening for GC in both ethnic groups, because extended
      atrophy may cause spontaneous disappearance of H. pylori from the stomach.

PMID- 11509114
TI  - Glucose intolerance, plasma insulin levels, and colon adenomas in Japanese men.
AB  - Hyperinsulinemia may be related to colon carcinogenesis. Several studies have
      suggested that diabetes mellitus is related to increased risk of colon cancer. We
      examined cross-sectionally the relation of fasting plasma insulin levels and
      glucose tolerance status to colon adenomas. In a consecutive series of 951 men
      undergoing total colonoscopy for a health examination at the Japan Self Defense
      Forces Fukuoka Hospital from April 1998 to August 1999, we identified 233 cases
      of colon adenomas and 497 controls with normal colonoscopy. Glucose tolerance
      status was determined by a 75-g oral glucose tolerance test, and subjects were
      classified as normal, impaired glucose tolerance (IGT) or non-insulin dependent
      diabetes mellitus (NIDDM). Plasma insulin levels were measured after subjects had
      fasted overnight. Logistic regression analysis and analysis of covariance was
      used to control for age and obesity. While plasma insulin levels were unrelated
      to colon adenomas, NIDDM was associated with a significantly increased risk of
      colon adenomas. There was no association between IGT and colon adenomas. NIDDM
      was more strongly associated with proximal colon adenomas. The findings suggest
      that long-term hyperinsulinemic status associated with NIDDM may increase the
      risk of colon adenomas, and subsequently of colon cancer.

PMID- 11509115
TI  - Role of Atp7b gene in spontaneous and N-diethylnitrosamine-induced carcinogenesis
      in a new congenic strain, WKAH.C-Atp7b rats.
AB  - To examine whether Long-Evans Cinnamon (LEC) rats, a mutant rat model of Wilson's
      disease, have a susceptibility gene(s) to hepatocarcinogenesis in addition to the
      causative gene, Atp7b, we established a new congenic strain, WKAH.C-Atp7b rats,
      in which the Atp7b gene of the LEC rats is inserted into the normal Wistar-King
      Aptekman Hokkaido (WKAH) background. Hepatocellular tumors developed
      spontaneously in both sexes of WKAH.C-Atp7b rats, their incidence being slightly
      lower than that in LEC rats. Incidences of spontaneous liver tumors in LEC,
      WKAH.C-Atp7b and WKAH rats correlated with hepatic copper and iron
      concentrations. Medium-term liver bioassay showed that LEC rats were more
      susceptible to the induction of glutathione S-transferase placental form-positive
      preneoplastic foci than WKAH.C-Atp7b rats, and WKAH.C-Atp7b rats were more
      susceptible than WKAH rats. In an N-diethylnitrosamine (DEN)-induced long-term
      carcinogenicity study, 1) LEC rats were similarly or rather less susceptible to
      hepatocellular tumors than WKAH.C-Atp7b and WKAH rats, indicating that the
      progression of the preneoplastic foci to liver cancer in LEC rats was worse than
      that in WKAH.C-Atp7b and WKAH rats, 2) the incidences of kidney tumors in LEC and
      WKAH.C-Atp7b rats were higher than that in WKAH rats and high copper
      concentrations in the kidneys were observed in LEC and WKAH.C-Atp7b rats, 3) LEC
      rats were resistant to lung carcinogenesis. These data indicate that the
      susceptibility of LEC rats to liver and kidney carcinogenesis could be explained
      by Atp7b gene mutation and that the susceptibility to lung carcinogenesis is
      controlled by gene(s) other than Atp7b.

PMID- 11509116
TI  - Inhibition of DNA adduct formation and mutagenic action of 3-amino-1-methyl-5h
      pyrido[4,3-b]indole by chlorophyllin-chitosan in rpsL transgenic mice.
AB  - We have studied the inhibitory effect of chlorophyllin-chitosan (Chl-Chi)
      complex, an insoluble form of chlorophyllin, on the DNA adduct formation and
      mutagenesis by a heterocyclic food mutagen-carcinogen, 3-amino-1-methyl-5H
      pyrido[4,3-b]indole (Trp-P-2), in mice carrying the E. coli rpsL gene as a
      mutagenesis reporter. Upon administration of a diet containing 0.002% or 0.01%
      Trp-P-2, DNA adducts were formed in various tissues in a dose-dependent manner,
      with the maximum level observed in the liver. Addition of 3% Chl-Chi to the diet
      reduced the Trp-P-2 adduct by up to 90%. The rpsL mutant frequencies increased
      significantly in both the liver and spleen upon administration of a 0.01% Trp-P-2
      diet. Addition of Chl-Chi to the diet decreased these induced mutant frequencies
      to the background level. No harmful effect of Chl-Chi was detected during these
      experiments. The results show that Chl-Chi may be a candidate chemopreventive
      agent against the genotoxic action of Trp-P-2, and possibly also other aromatic
      carcinogens in the diet.

PMID- 11509117
TI  - Frequent increase of DNA copy number in the 2q24 chromosomal region and its
      association with a poor clinical outcome in hepatoblastoma: cytogenetic and
      comparative genomic hybridization analysis.
AB  - In a cytogenetic and comparative genomic hybridization (CGH) study of 38
      hepatoblastomas, we found gain of 1q in 17 tumors (44.7%), that of 2 / 2q in 14
      (36.8%), that of 20 / 20q in 9 (23.7%) and that of 8 / 8q in 8 (21.0%), loss of
      4q in 4 (10.5%) and no DNA copy changes with normal karyotype or no mitotic cells
      in 11 (28.9%). Eleven tumors with 2 / 2q gain detected by CGH had a total
      chromosome 2 gain, a partial 2q gain, or a total chromosome 2 gain with an
      augmented partial 2q region; the common region for DNA copy gain was 2q24. Two
      color fluorescence in situ hybridization (FISH) analyses using probes covering
      the centromere of chromosome 2 or HOXD13 (2q31) confirmed the CGH findings, and
      showed that the common region for gain in 2q was centromeric to HOXD13. Event
      free survival (EFS) +/- standard error (SE) at 5 years was lowest in patients
      with 2q gain [37 +/- 15%], highest in those with no DNA copy changes [82 +/-
      12%], and intermediate in those with DNA copy changes other than 2q gain [74 +/-
      13%] (P = 0.0549). Multivariate analysis showed that 2q gain was an independent
      factor predicting a poor outcome. These findings suggest the presence of a growth
      promoting gene or an oncogene in the 2q24 chromosome band, and a tumor suppressor
      gene in terminal 4q, which have important roles in the development and
      progression of hepatoblastoma.

PMID- 11509118
TI  - Detection and cloning of a protein recognized by anti-human prostate-specific
      antigen (PSA) antibody in the rat ventral prostate.
AB  - Prostate-specific antigen (PSA), a 33 kDa glycoprotein produced in the epithelium
      of the human prostate, has become established as a useful tumor marker for
      prostate cancer in man. Since reports of homologous proteins in animals other
      than primates have been lacking, the present investigation was carried out to
      identify any PSA-like protein in rats. Immunoblot analysis using a specific
      monoclonal anti-human PSA antibody detected a 32 kDa immunoreactive protein in
      the ventral lobe of the rat prostate, but not in other lobes or in other tissues.
      Positive immunostaining was observed only for the luminal surface of the
      glandular epithelium and the intraductal fluid in the ventral prostate. Sequence
      analysis of a cDNA for the rat PSA-like protein, cloned by immunoscreening of an
      expression cDNA library prepared from the ventral lobe, revealed identity to the
      rat submaxillary gland S3 kallikrein. Human PSA also belongs to the kallikrein
      family. Thus, this protein produced in the rat ventral prostate was suggested to
      be a possible counterpart of human PSA.

PMID- 11509119
TI  - Expression of Periostin, homologous with an insect cell adhesion molecule, as a
      prognostic marker in non-small cell lung cancers.
AB  - We used our palindromic polymerase chain reaction (PCR)-driven cDNA differential
      display technique to identify and isolate a gene, designated periostin, from
      cancer tissues and found it to be overexpressed in several human tumors. We
      attempted to determine the influence of periostin expression on clinical outcome
      in patients with non-small cell lung cancer (NSCLC) by reverse transcriptase (RT)
      PCR analysis. Periostin gene was highly expressed at the tumor periphery of lung
      cancer tissue but not within the tumor by in situ RNA hybridization, suggesting
      that expression of periostin may be involved in the process of tumor invasion.
      Periostin transcripts were detected in 50 (49.0%) of the tumor samples, although
      some paired normal lung samples showed weak expression. There was no relationship
      between periostin gene expression and gender, N- or T-status. The NSCLC patients
      with periostin expression had significantly poorer survival than the patients
      without periostin expression (P = 0.0338).

PMID- 11509120
TI  - SGLT gene expression in primary lung cancers and their metastatic lesions.
AB  - Cancer cells show increased glucose uptake and utilization in comparison with
      their normal counterparts. Glucose transporters play an important role in glucose
      uptake. We previously reported the differential gene expression of the GLUT
      family in primary and metastatic lesions of lung cancer. To investigate the role
      of Na( +) / glucose cotransporter (SGLT) genes in cancers, we examined the levels
      of expression of SGLT1 and SGLT2 genes in primary lung cancers and their
      metastatic lesions. Ninety-six autopsy samples (35 primary lung cancers, 35
      corresponding normal lung tissues, 10 metastatic liver lesions, and 16 metastatic
      lymph nodes) from 35 patients were analyzed for SGLT1 and SGLT2 expression by
      reverse transcription (RT)-polymerase chain reaction (PCR). There were no
      significant differences in the level of expression of either gene between the
      primary lung cancers and normal lung tissues. The level of SGLT1 expression in
      the metastatic lesions and primary lung cancers did not differ significantly. The
      level of SGLT2 expression was, however, significantly higher in the metastatic
      lesions of both the liver and lymph node than in the primary lung cancers. These
      results suggest that SGLT2 plays a role in glucose uptake in the metastatic
      lesions of lung cancer.

PMID- 11509121
TI  - Enhanced formation of azoxymethane-induced colorectal adenocarcinoma in
      gammadelta T lymphocyte-deficient mice.
AB  - T cell receptor (TCR) gammadelta-positive T lymphocytes, which are localized
      mostly within the intraepithelial space of intestinal epithelium, have been
      suggested to play a role in maintaining the normal configuration of intestinal
      epithelium. However, the role of TCRgammadelta-positive T lymphocytes in the
      formation and progression of colorectal adenocarcinoma that originates from
      colorectal epithelial cells remains to be elucidated. In this study, TCRalphabeta
      and TCRgammadelta-positive T lymphocyte-deficient mice (homozygous TCRa and TCRd
      gene knockout mice) and the background wild-type mice were administered
      azoxymethane, and the formation of macroscopic tumors and microscopic aberrant
      crypt foci in colorectal mucosa were compared among the three types of mice. Well
      differentiated adenocarcinoma appeared 5 months after 5 administrations of
      azoxymethane (10 mg/kg weight) only in a few TCRd -gene knockout mice and the
      frequency of the carcinoma-bearing mice was increased at 7 and 9 months after the
      administration. Aberrant crypt foci were also detected in the colorectal mucosa
      of TCRd -gene knockout mice to a greater extent than in colorectal mucosa of TCRa
      gene knockout mice 1 month after the azoxymethane administration. These results
      suggest that TCRgammadelta-positive T lymphocytes, which are present mainly in
      the intraepithelial space, play a role in suppression of the formation and
      progression of colorectal adenocarcinoma in mice.

PMID- 11509122
TI  - Reversing effect of agosterol A, a spongean sterol acetate, on multidrug
      resistance in human carcinoma cells.
AB  - The effect of agosterol A, a novel polyhydroxylated sterol acetate isolated from
      a marine sponge, on P-glycoprotein (P-gp)-mediated multidrug-resistant cells (KB
      C2) and the multidrug resistance associated protein (MRP1)-mediated multidrug
      resistant cells (KB-CV60) was examined. Agosterol A reversed the resistance to
      colchicine in KB-C2 cells and also the resistance to vincristine in KB-CV60 cells
      at 3 to 10 microM concentration. Agosterol A at 3 mM increased the vincristine
      concentration in both KB-C2 cells and KB-CV60 cells to the level in parental KB-3
      1 cells. Agosterol A also decreased the efflux of vincristine from both KB-C2
      cells and KB-CV60 cells to the level seen in KB-3-1 cells. Agosterol A inhibited
      the [(3)H]azidopine-photolabeling of P-gp and also inhibited the uptake of
      [(3)H]S-(2,4-dinitrophenyl)glutathione (DNP-SG) in inside-out membrane vesicles
      prepared from KB-CV60 cells. We conclude that agosterol A directly inhibited drug
      efflux through P-gp and/or MRP1.

PMID- 11509124
TI  - Simultaneous intraluminal thermobrachytherapy: an in vitro study.
AB  - A multi-institutional study on simultaneous intraluminal thermobrachytherapy
      (SITB) for advanced esophageal cancer was conducted in Japan. In this study,
      brachytherapy was administered by a small radioactive source stepping through a
      catheter in the esophagus, and hyperthermia was also applied by an endoesophageal
      coil. However, experimental or clinical findings on the spatial distribution of
      its antitumor effects around the esophagus are not available. Therefore, we
      developed an in vitro model of SITB using a high-dose-rate iridium-192 stepping
      source and two human cancer cell lines (WiDr and A549), and determined the
      spatial distribution of the antitumor effects. According to this model, the
      antitumor effects steeply decreased as the source-cell distance increased when
      cells of both cell lines were irradiated with 5 Gy without heat. When WiDr cells,
      a more resistant cell line to radiation and heat, were simultaneously irradiated
      and heated for 30 min at 44 degrees C, the effects decreased much less steeply as
      the distance increased. For A549 cells, a more sensitive cell line, irradiation
      with hyperthermia even at 42 degrees C made the decrease in the effects smaller.
      The largest antitumor effects can be expected at 5 - 10 mm beneath the esophageal
      mucosa, where the endoesophageal coil can heat tissues most effectively. SITB can
      induce larger antitumor effects than brachytherapy alone, especially in
      submucosal disease, which would favor treatment of advanced cancer.

PMID- 11509123
TI  - Anticancer drug-mediated induction of multidrug resistance-associated genes and
      protein kinase C isozymes in the T-lymphoblastoid cell line CCRF-CEM and in
      blasts from patients with acute lymphoblastic leukemias.
AB  - The major determinants mediating drug resistance in acute lymphoblastic leukemias
      (ALL) unresponsive to chemotherapy, are still unclear. For example, it is still
      unknown whether selection or induction processes are responsible for drug
      resistance here or whether protein kinase C (PKC) isozymes contribute to the
      resistant phenotype. Therefore, inducibility of resistance factors or PKC
      isozymes genes was examined in CCRF-CEM cells treated with diverse anticancer
      drugs--adriamycin, camptothecin, etoposide or vincristine--at sublethal
      concentrations for 24 h. MDR1, MRP1, LRP and PKC isozyme alpha, beta(1), beta(2),
      epsilon, iota, eta, theta, zeta gene expression was determined by cDNA-PCR. We
      found significant dose-dependent, mostly combined, induction of the MDR1, MRP1
      and LRP genes. Significantly enhanced gene expression of the majority of PKC
      isozyme genes was found after treatment with camptothecin. PKCzeta was
      upregulated throughout by each anticancer drug applied in this setting. A series
      of selected CCRF-CEM-derived multidrug resistance (MDR) sublines also showed
      enhanced expression of the PKC isozymes compared to the parental cell line. MDR1
      and PKCeta gene expression levels were correlated highly significantly. Blasts
      from two patients with ALL during the first week of monotherapy with steroids
      revealed combined induction of the MDR1, multidrug resistance-associated protein
      1 (MRP1), lung cancer resistance-related protein (LRP) and most PKC isozymes,
      predominantly PKCzeta. Another patient with T-ALL, who failed to respond to four
      months of intensive chemotherapy, showed an enhanced MRP1 gene expression
      combined with markedly overexpression of PKCeta and PKCtheta. Furthermore, the
      camptothecin and etoposide-mediated induction of resistance factors in the CCRF
      CEM cell line could be suppressed by staurosporine, a rather unspecific inhibitor
      of protein kinases. However, selective inhibitors of PKC isozymes
      (bisindolylmaleimide GO 6850, indolocarbazole GO 6976) produced no significant
      effects here. Therefore, the PKC isozymes eta, theta and zeta are of interest as
      potential targets to overcome drug resistance in ALL.

PMID- 11509125
TI  - [Studies on cloning and expression of hepatitis B virus x gene].
AB  - OBJECTIVE: To express and purify the x gene of hepatitis B virus (HBV), and then
      the purity of the protein could specifically be analysed by the human antibodies
      against HBV x antigen (protein). METHODS: HBV x gene was amplified from the
      complete genome by PCR, and cloned in the pGEX-2T fused expression vector. After
      transforming the plasmid into E.coli, the recombinant with HBx gene was obtained.
      The fusion protein was generated with E.coli fused expression system and purified
      with affinity chromatography. RESULTS: The HBx protein could be applied to
      detecting specific antibody of hepatitis B virus patients. CONCLUSIONS: The
      purity of the HBx protein can specifically be recognized by the human antibodies
      against HBV x antigen.

PMID- 11509126
TI  - [Fas and ICE expression in the hepatocytes of tupaia with HDV/HBV infection].
AB  - OBJECTIVE: To investigate the relationship between Fas and ICE expression and HDV
      infection. METHODS: HDAg, Fas, and ICE were determined in 45 liver tissue
      specimens of tupaia with HDV/HBV infection by immunohistochemistry. RESULTS: Fas
      was detected in 39 out of 45 liver tissue specimens (86.7%), and ICE in 43
      (95.6%). Fas and ICE were located in the cytoplasm or/and the membrane of
      hepatocytes, especially in the cytoplasm. There was significant correlation
      between the expression of HDAg and the expression of Fas and ICE (chi(2)=29.2 and
      36.2, respectively, P<0.01). CONCLUSIONS: The expression of Fas and ICE may be
      induced by HDAg in hepatocytes.

PMID- 11509127
TI  - [The inhibitory effect of oxymatrine on hepatitis C virus in vitro].
AB  - OBJECTIVE: To study the inhibitory effect of oxymatrine on HCV in vitro. METHODS:
      SMMC-7721 cells transfected with pBK-HCV using lipofectin transfection protocal
      were treated with oxymatrine. bDNA signal amplification assay and MTT
      colorimetric assay were used for intracellular HCV RNA and cytotoxicity. RESULTS:
      The stable HCV expression cell model established here could be used as a tool for
      medicine screen. Oxymatrine at the concentration of 100~1000 mug/ml could
      significantly decrease the level of intracellular HCV RNA. No cytotoxicity was
      shown in such concentrations. CONCLUSIONS: Oxymatrine has an anti-HCV potential
      activity in vitro.

PMID- 11509128
TI  - [Effects of tumor necrosis factor alpha on the expression of connective tissue
      growth factor in hepatic stellate cells].
AB  - OBJECTIVE: To investigate the effect of tumor necrosis factor alpha (TNF-alpha)
      on the expression of connective tissue growth factor (CTGF) in rat hepatic
      stellate cells (HSC) in vitro. METHODS: HSCs were prepared from SD rats by in
      situ perfusion and single-step Nycodenz gradient, and were treated with TNF-alpha
      and TGF-beta 1. The expression of CTGF in HSC was assessed using reverse
      transcription-polymerase chain reaction (RT-PCR). RESULTS: Both TNF-alpha and TGF
      beta 1 could stimulate the expression of CTGF mRNA in HSC. The expression of CTGF
      was not found in HSC after treatment with TNF-alpha(10microgram/L) for 6 hours,
      but was observed after TNF-alpha treatment for 24 and 48 hours. TGF-beta1 could
      induce the mRNA expression for CTGF just after 6 hours of treatment at
      1microgram/L concentration. CONCLUSIONS: TNF-alpha is able to induce the
      expression of CTGF in HSC, and this may be one of the mechanisms for TNF-alpha
      involving in the liver fibrosis.

PMID- 11509129
TI  - [Changes of lipid peroxidation in liver fibrogenesis induced by
      dimethylnitrosamine and drugs' intervention].
AB  - OBJECTIVE: To investigate the pathological actions of lipid peroxidation
      implicated in liver fibrogenesis induced by dimethylnitrosamine (DMN), and the
      mechanism of Fuzheng Huayu 319 decoction (319 decoction) and interferon-gamma
      (IFN-gamma) actions against liver fibrosis. METHODS: A liver fibrotic model was
      induced by intraperitoneal injection of DMN in rats, and treated with 319
      decoction and IFN-gamma, respectively. The liver sections were stained with HE
      and ponceau for collagens, and the liver functions were assayed. The contents of
      hepatic hydroxyproline (Hyp) and malondialdehyde (MDA) and the activities of
      superoxide dismutase (SOD) were measured. The correlation among SOD, MDA and Hyp
      was analyzed. RESULTS: In the models, hepatic collagens proliferated remarkably
      and fibrous septa were formed. Serum ALT activities increased. Both Hyp and MDA
      enhanced obviously, but SOD decreased markedly. SOD was significantly negatively
      correlated with MDA and Hyp, respectively (r=-0.70, -0.73, P<0.01), and MDA was
      significantly positively correlated with Hyp (r=0.88, P<0.01). While both 319
      decoction and IFN-gamma attenuated collagen proliferation and deposition,
      decreased ALT level, increased SOD activity, but decreased MDA and Hyp contents.
      CONCLUSIONS: DMN can cause hepatic lipid peroxidation, which is closely involved
      in liver fibrogenesis induced by DMN. The effect against hepatic lipid
      peroxidation is one of the important mechanisms of 319 decoction and IFN-gamma
      actions against liver fibrosis.

PMID- 11509130
TI  - [Effects of intestinal endotoxemia on the development of cirrhosis in rats].
AB  - OBJECTIVE: To explore the effect of endotoxin on the development of cirrhosis.
      METHODS: The cirrhosis model with intestinal endotoxemia was made by oral intake
      of 0.03% thioacetamide for four months to observe the effect of endotoxin on the
      hepatic collagen contents in both thioacetamide and thioacetamide +
      lipopolysaccharide groups and to detect the contents of tumor necrosis factor
      alpha (TNF-alpha), endothelin-1 (ET-1), nitric oxide (NO), and malondialdehyde
      (MDA) in the plasma and the hepatic homogenate. RESULTS: The contents of TNF
      alpha, ET-1, NO, and MDA in the plasma and the hepatic homogenate and the content
      of collagen in the hepatic tissue in the two groups were higher than those in the
      normal control group. CONCLUSIONS: Endotoxin can accelerate liver fibrosis and
      the formation of cirrhosis.

PMID- 11509131
TI  - [Annexin V technique for the study of liver damage].
AB  - OBJECTIVE: To evaluate Annexin V technique for measuring hepatic apoptosis and to
      investigate the protective function of Rg1 and Rb1 on acute liver injury.
      METHODS: LPS-treated acute liver injury and the protective effect of Rg1 and Rb1
      were assessed by Annexin V double staining and PI staining measurements. The
      activity of sPLA(2) was measured by [(3)H]-labelled oleic acid method. RESULTS:
      Annexin V showed a higher sensitivity and specificity than PI staining. It was
      only the Annexin V assay that could discriminate normal cells, apoptosis cells,
      and necrotic cells. Rg1 and Rb1 could reduce the percentage of hepatic apoptotic
      and necrotic cells (P<0.01) and activity of sPLA2 (P<0.01). CONCLUSIONS: The
      Annexin V assay is an ideal method for measuring apoptosis presently. Rg1 and Rb1
      have a definite protective effect on acute liver injury in rats.

PMID- 11509132
TI  - [Overexpression of p27(KIP1) induced by Bak gene leads to the arrest in G(1)
      phase of HCC-9204 cell line].
AB  - OBJECTIVE: To explore whether p27(KIP1) plays an important role in prolonging
      cell cycle in G(1) phase and leading to apoptosis of HCC-9204 cells. METHODS: A
      model of Bak-induced cell cycle arrest in G(1) phase and subsequent apoptosis was
      established. p27(KIP1) was obtained from the model and sequenced afterwards. A
      zinc inducible p27(KIP1) stable transfectant was constructed. The effects of
      inducible p27(KIP1) on cell growth and cell cycle arrest were examined in control
      pMD and pMD-KIP1 transfected HCC-9204 cells. Western blot was performed to
      evaluate the expression of p27(KIP1). RESULTS: The cell growth was reduced by 35%
      upon 48h of p27(KIP1) induction with zinc treatment as determined by trypan blue
      exclusion assay. p27(KIP1) caused cell cycle arrest at 24h after induction, with
      40% increase in G(1) population. CONCLUSIONS: Bak may induce cell cycle arrest in
      G(1) phase through up-regulating expression of p27(KIP1). The inducible p27(KIP1)
      expressing cells provide a model to assess p27(KIP1) function.

PMID- 11509133
TI  - [Cloning and sequence analysis of light chain gene of human antibody against HBV
      pre-S2].
AB  - OBJECTIVE: To obtain the gene of light chain of human antibody against HBV pre
      S2. METHODS: A human antibody against HBV pre-S2 displayed on phage was obtained
      from the constructed human immunoglobulin phage displaying library through four
      rounds panning of "adherence-elution-amplification" with Pre-S2 (120aa-145aa)
      short peptide synthesized and help phage. The positive clone of anti-pre-s2 was
      characterized by ELISA competitive inhibition assay. The plasmid from the
      positive clone was amplified by PCR with designed oligonucleotide primers of kaph
      light chain. The light chain fragment was amplified with PCR and plasmid pUC18
      digested by restriction endonuclease SacI & XbaI, respectively, then it was
      subcloned into the plasmid pUC18 and was transformed into E.coli XL1-blue
      sensitized by CaCl2. The recombinant plasmid pUC18-kaph was sequenced. RESULTS:
      The competitive inhibition rate of the positive clone of anti-pre-S2 was 65% at
      1:50 dilution. Sequence was compared with data in gene bank through internet and
      analyzed with Blast. According to the sequence and ELISA competitive inhibition
      assay the integral gene of kaph light chain of human antibody against HBV-PreS2
      was obtained. Its variable region located on 1-328bp including three
      hypervariable regions (82-105bp, 145~177bp, 274~309bp) and four frame regions (1
      81bp, 106-144bp, 178-273bp, 310-328bp). Its constant region was located on 329
      645bp. CONCLUSIONS: The HBV pre-S2 kaph light chain is screened from phage
      antibody displaying library by antigen-antibody special response.

PMID- 11509134
TI  - [Effect of Xue Zhi Kang on the formation of fatty liver in cholesterol-fed
      rabbits].
AB  - OBJECTIVE: To explore the effect of Xue Zhi Kang (XZhK) on the formation of fatty
      liver in cholesterol-fed rabbits. METHODS: XZhK was refined from Chinese
      traditional medicine Hong Qu and its main composition is HMG-CoA reductase
      inhibitor. Thirty New Zealand white rabbits were randomly assigned into 3 groups
      (control, hypercholesterol-fed, and XZhK groups) during the 12 week's experiment.
      The effects of XZhK (0.8g.kg(-1).d(-1)) were investigated in rabbits fed a l.5%
      cholesterol diet. The changes of serum TC, TG, HDL-C, and LDL-C concentrations
      and the histopathological changes of the liver were detected. RESULTS: The serum
      TC, LDL-C, and TG levels decreased in XZhK group compared with those in the
      cholesterol-fed control group (P<0.05 ). The serum HDL-C concentration slightly
      increased, but there was no statistical significance. The fatty degeneration of
      liver was ameliorated in XZhK group (P<0.05). CONCLUSIONS: XZhK can modulate the
      lipid metabolism and inhibit the formation of fatty liver in cholesterol-fed
      rabbits.

PMID- 11509135
TI  - [Effects of vascular endothelial growth factor on adhesion molecular expression
      of hepatocellular carcinoma HepG].
AB  - OBJECTIVE: To study the effect of vascular endothelial growth factor (VEGF) on
      homotypic adhesion and E-cadherin of hepatocellular carcinoma cells. METHODS: We
      measured the function of homotypic adhesion with (3)H-TdR infiltration and the
      expression of E-cadherin with laser scanning confocal microscope. RESULTS: After
      60, 90, 120min, the values (dpm/min) of (3)H-TdR infiltration in HepG(2) cells
      induced by 1ng/ml, 5ng/ml VEGF were 1758.67+/-289.46, 1380.03+/-328.55, 2657.43
      +/- 310.31 and 3124.30+/-262.14, 2245.60+/-273.24, 2091.52+/-213.84. The values
      by 10ng/ml VEGF were 1232.32+/-201.04, 2337.50+/-333.04, 2236.99 +/- 237.07,
      which were significantly lower than those in control group (P<0.05 or 0.01). The
      expression of E-cadherin in hepatocellular carcinoma cells induced by 5ng/ml VEGF
      was 352+/-56 and much lower than that in control group (757+/-103, P<0.01).
      CONCLUSIONS: VEGF can decrease homotopic adhesion of hepatocellular carcinoma
      HepG(2) cell, which is connected with the less expression of E-cadherin in
      hepatocellular carcinoma HepG(2) cell.

PMID- 11509136
TI  - [Improvement of proliferation of intrasplenically transplanted fetal hepatocytes
      after immunoadsorption].
AB  - OBJECTIVE: To investigate whether removing the compartments of hemopoietic stem
      cells by immunoadsorption would improve the proliferation of fetal hepatocytes
      after transplantation. METHODS: The purification of fetal hepatocytes was
      performed by immunoadsorption, and the proliferative capability of fetal
      hepatocytes after intrasplenic transplantation was evaluated by image analysis
      and flowcytometry analysis. RESULTS: The yield of fetal hepatocytes after
      immnoadsorption was (2~3)+/-10(7) in total per fetal liver and the viability is
      over 85%. The square densities of fetal hepatocytes with image analysis at 3, 7,
      and 14 days after transplantation were (1603+/-337), (3788+/-605), (8129+/-1025)
      micrometer(2)/mm(2), and the adult hepatocytes were (1007+/-128), (2013+/-242),
      (3780+/- 772) mum(2)/mm(2) accordingly. The S phase rates of fetal hepatocytes by
      flowcytometry analysis were (14.25+/-4.11)%, (16.07+/-5.35)%, and (17.32+/
      5.17)%, and the rates of adult hepatocytes were (5.66+/-1.02)%, (4.98+/- 0.74)%,
      and (6.83+/-1.37)% correspondingly. The S phase rates and the square densities of
      fetal hepatocytes were significantly higher than those of adult hepatocytes.
      CONCLUSIONS: Fetal hepatocytes are highly proliferative and potentially suitable
      as donor cells in hepatocytes transplantation after immunoadsorption.

PMID- 11509137
TI  - [Therapeutic potential of recombinant adenovirus expressing p53 in hepatocellular
      carcinoma cell lines].
AB  - OBJECTIVE: To investigate the effects of the recombinant adenoviral vector Ad-p53
      on the biological behavior of hepatocellular carcinoma (HCC) cells in vitro and
      in vivo. METHODS: With recombinant adenoviral vector expressing WT-p53 (Ad-p53),
      p53 gene was transfected into the HCC cell line, PLC/PRF/5. The cytotoxicities of
      Ad-p53 to cells were measured by MTT assay. Cell growth properties and cell cycle
      patterns were assessed with flow cytometry. The animal model was developed by
      injecting HCC cells into the dorsum of nude mice. Ad-p53 was injected
      intratumorally. The animals were killed, and then excised tumors were weighed and
      analyzed for p53 and p21 protein expression using western blot assay. RESULTS:
      The introduction of exogenous wild-type p53 resulted in the inhibition of cell
      growth, high G2/M ratio and cell apoptosis, and low S ratio in PLC/PRF/5. The
      expression of both p53 and p21 proteins was upregulated in the cells.
      CONCLUSIONS: Replication-deficient adenoviral vector expressing WT-p53 may be
      useful for gene therapy of HCC.

PMID- 11509138
TI  - [Construction and expression in eukaryotic cells of HBsAg and B].
AB  - OBJECTIVE: To investigate the enhanced role of B(7-1) in gene immunization of
      eukaryotic vector expressing HBsAg, and further to eliminate the immunotolerance
      to hepatitis B virus. METHODS: B(7-1) and IRES-HBs with linker and promoter
      sequence prior to HBs gene were amplified with high fidelity PCR, then subcloned
      into plasmid pBluescriptks+, which was used to sequence. The eukaryotic
      expressing vector was constructed by inserting B(7-1) and IRES-HBs into plxsn.
      Recombinant vector was transfected into PA317 by means of lipid mixtures. Titre
      of pseudovirus packaged in PA317 cells was detected by infecting NIH3T3 cells.
      B(7-1) and HBsAg expression in PA317, NIH3T3, HepG(2), 293, EL4 cell lines was
      detected by RT-PCR, immunohistochemistry and ELISA, respectively. RESULTS: No
      change was found in the sequences of target genes amplified by high fidelity PCR
      compared with the known sequences. Plxsn-B(7-1)-HBs was constructed by first
      inserting B(7-1) into plxsn with enzyme EcoRI/XhoI, then IRES-HBs was inserted in
      the same way with enzyme XhoI/BamHI. 43 and 90 G418-resistant clones were
      obtained two weeks later after 1:10 and 1:5 passages at 24 hours after
      transfection. Titre of the peudovirus was 5.4x10(5) CFU/ml. B(7-1) was expressed
      in all the cell lines above by RT-PCR test. The contents of HBsAg in the
      supernatant of the PA317, NIH3T3, HepG(2), and 293 cells at 24, 48, 72 hours
      intervals were 0.15, 0.11, 0.20, 0.13; 0.63, 0.47, 0.76, 0.58; 0.77, 0.61, 0.89,
      0.69, respectively. CONCLUSIONS: The retroviral vector expressing B(7-1) and
      HBsAg simultaneously is constructed successfully. The target antigens are
      expressed in above cell lines in vitro after transfection with lipids mixtures.
      It may be used to conduct gene immunization and to investigate the role of B(7-1)
      on HBsAg immune response, which may be further used to the prevention and therapy
      of hepatitis B.

PMID- 11509139
TI  - [Modulation of angelica sinensis polysaccharides on the expression of nitric
      oxide synthase and Bax, Bcl-2 in liver of immunological liver-injured mice].
AB  - OBJECTIVE: To investigate the modulation of Angelica Sinensis Polysaccharides on
      the expression of nitric oxide synthase and Bax, Bcl-2 in the liver of
      immunological liver injured mice. METHODS: Immunological liver injury was induced
      by lipopolysaccharide (ip, 2mug/10g) in bacillus calmette-guerin (ip, 1mg/10g,
      qd/1 d) primed mice. Angelica Sinensis Polysaccharides was administrated to the
      mice with 30mg/kg, 60mg/kg, respectively. The effects of Angelica Sinensis
      Polysaccharides on the expression of nitric oxide synthase, Bcl-2, and Bax gene
      were assessed by immunohistochemistry, and the nitric oxide (NO) production,
      alanine transaminase (ALT) activity, glutathione S-transferase (GST) activity in
      serum were determined. RESULTS: The levels of NO, sALT, and sGST were
      significantly higher in immunological liver-injured mice than controls. The
      contents of iNOS and Bax were 17.8 times (P<0.001) and 1.31 times (P<0.05) of
      control values, respectively. cNOS expression was not obviously changed, and no
      Bcl-2 expression was found in immunological liver-injured mice. Angelica Sinensis
      Polysaccharides of 30mg/kg could reduce the levels of NO, sALT, and sGST by
      24.6%, 40.8%, and 18.4%, respectively; the expression of iNOS and Bax decrease by
      84.2% and 37.1%; and the expression of cNOS, Bcl-2 increase by 66.8% and 3.38
      times, respectively. The influence of Angelica Sinensis Polysaccharides of
      60mg/kg was not so obvious as that of 30mg/kg on sGST, NO, cNOS, Bax, and Bcl-2,
      but was more effective on sALT and iNOS. CONCLUSIONS: NO production may play a
      role in the LPS-induced hepatotoxicity. Angelica Sinensis Polysaccharides can
      alleviate the immune liver injury by modulating the expression of cNOS, iNOS,
      Bax, Bcl-2.

PMID- 11509140
TI  - [Clinical study on hepatitis D virus-positive patients died from severe hepatitis
      B].
AB  - OBJECTIVE: To investigate the role of hepatitis D virus (HDV) in the development
      of severe hepatitis B. METHODS: Seventy-six HDV-positive patients died from
      severe hepatitis B were compared with 244 HDV-negative patients from severe
      hepatitis B in clinical manifestations, signs, complications and main biochemical
      indexes at the same period. RESULTS: HDV-positive patients had obvious ascites,
      abdominal distension, digestive tract hemorrhage as compared with the HDV
      negative ones (P<0.05). There were significant differences in hepatorenal
      syndrome, bacterial infection, manifold complications, the levels of total
      bilirubin and alanine aminotransferase, and the activity of prothrombin between
      the patients of the two groups (P<0.01). CONCLUSIONS: HDV can aggravate severe
      hepatitis B.

PMID- 11509141
TI  - [A retrospective analysis of therapeutic outcome of various types of severe virus
      hepatitis].
AB  - OBJECTIVE: To explore combined therapeutic schemes for severe virus hepatitis and
      to raise survival rate. METHODS: The therapeutic outcomes of different schemes
      were analyzed in 1020 cases of severe viral hepatitis treated in our hospital in
      recent twenty years. The treatments were classified as basic and combination of
      Chinese traditional and Western medicine therapies in which embryonic liver cell
      suspend liquid or hepatic growth factor, or/and artificial liver as blood cleaner
      were also used for the latter. RESULTS: The survival rate was 30.28% (33/109)
      treated by basic procedures and 60.15% (548/911) by combined procedures. There
      was obvious statistical difference in survival rate between the two groups
      (P<0.001). Among all the patients, 219 (21.47%) suffered from acute or sub-acute
      severe hepatitis, 801 (78.53%) chronic severe hepatitis; 446 started their
      treatment at the early stage of the disease and the survival rate was 77.13%
      (344/446); 404 at the mid stage and 170 at the late stage and the survival rates
      were 52.72% (213/404) and 14.12% (24/170), respectively. The survival rate for
      the patients treated at the early or the mid stage was much higher than that at
      the late stage (P<0.001), and had a positive correlation with the activity of
      prothrombin. CONCLUSION: The combined therapies used in present study are
      effective to raise the survival rate of the patients with severe virus hepatitis.
      Early treatment is extremely important for the patients' prognosis.

PMID- 11509142
TI  - [Relationship between serum matrix metalloproteinase-2 and metastasis and
      recurrence following radical hepatic resection in hepatocellular carcinoma].
AB  - OBJECTIVE: To study the relationship between serum matrix metalloproteinase-2
      (MMP-2) and metastasis and recurrence following radical hepatic resection in
      hepatocellular carcinoma (HCC). METHODS: Cox's proportional hazard model was used
      to determine the significant clinical factor of prognosis. Meanwhile, enzyme
      linked immunoadsordent assay (ELISA) and northern blot analysis were adopted to
      detect serum and tumor tissue levels of MMP-2 respectively in HCC patients.
      RESULTS: Cox's proportional hazard model showed that tumor size and tumor number
      were significant prognostic factors of HCC patients following hepatic resection
      (P=0.022 and P=0.040). According to this result, we divided HCC patients into
      high-tendency to metastasis recurrence and low-tendency to metastasis recurrence
      groups. Serum levels of MMP-2 in high-tendency to metastasis recurrence following
      radical hepatic resection group were significantly higher than those in low
      tendency group (26.39ng/m+/-2.64ng/ml vs 24.86ng+/-1.95ng/ml, P<0.05). Serum
      levels of MMP-2 in HCC patients performed non-radical hepatic resection group
      were also significantly higher than those in HCC patients performed radical
      hepatic resection group (29.43ng+/-3.12 ng/ml vs 25.72ng+/-2.45ng/ml, P<0.01).
      Northern blot analysis revealed that the changes of MMP-2 level in the serum were
      consistent with those of its mRNA level in the tumor tissue of HCC patients.
      CONCLUSIONS: Serum MMP-2 level is an indicator for metastatic recurrence
      following radical hepatic resection in HCC. The high levels of MMP-2 in the serum
      are due to high MMP-2 mRNA expression in the tumor tissue of HCC patients.

PMID- 11509143
TI  - [CT appearance and its diagnosis value in liver cancer after transcatheter oily
      chemoembolization combining with high intensity focused ultrasound therapy].
AB  - OBJECTIVE: To study the CT appearances of liver cancer after transcatheter oily
      chemoembolization (TOCE) combining with high intensity focused ultrasound (HIFU)
      therapy. METHODS: Fifty cases of clinically-proved liver cancer were included
      into this study. For each case, CT scanning before and after TOCE, HIFU treatment
      was performed. The volumes of the masses were measured. The appearances of the
      oily deposition and the density, shape, border of the lesions were observed.
      RESULTS: The lesions became smaller in 38 cases (38/50, 76%) after the treatment.
      The differences were detected statistically in the ratio of the tumor shrinkage
      between the single TOCE therapy and the combined treatment (P<0.05). The ratio of
      the tumor shrinkage was closely correlative with the quantity of the oily
      deposition, but not with the diameter of the tumor before treatment. The lowered
      densities were showed in 30 cases (30/50, 60%) and the borders became regular and
      clear in 16 cases after HIFU therapy. CONCLUSIONS: TOCE combining with HIFU
      therapy in the patients with liver cancer can make the tumor smaller. CT is of
      great value in the evaluation of efficacy and prognosis.

PMID- 11509144
TI  - [IFN-r/IL-4 expression in peripheral blood mononuclear cells of the patients with
      chronic severe hepatitis].
AB  - OBJECTIVE: To understand the expressions of interferon-r (INF-r) and interleukin
      4 (IL-4) in peripheral blood mononuclear cells (PBMCs) of the patients with
      chronic severe hepatitis (CSH). METHODS: PBMCs from the patients with CSH were
      separated routinely and stimulated by PMA/Ionomycin/Monensin. The production of
      IFN-r/IL-4 by CD4+ T cells in PBMC was determined by fluorescence activated call
      sorting (FACS) analysis and fluorescence-quantitative PCR assay for
      quantification of HBV DNA. RESULTS: The percentage of IFN-gamma-producing T cells
      in CD4+ T cells was higher in patients with CSH (7.2%-26.3%) than in normal
      controls (2.2%-11.9%) (P<0.01). The percentage of Th1 cells increased
      significantly with the raise of hepatic inflammation activity. The percentage of
      IL-4-producing T cells in CD4+ T cells did not differ significantly between
      patients with CSH and normal controls. The quantification of HBV DNA decreased
      significantly with the increase of the percentage of IFN-gamma-producing T cells.
      CONCLUSIONS: Th1 cell is associated with hepatic inflammatory activity and IFN
      gamma depresses HBV replication.

PMID- 11509145
TI  - [Serum markers and pathological evaluation in hepatitis fibrosis of chronic
      hepatitis B treated with interferon alpha].
AB  - OBJECTIVE: To evaluate the anti-fibrotic effect of interferon alpha and to study
      the relationship between the anti-fibrotic effect and the efficacy of anti-virus
      in patients with chronic hepatitis B treated with interferon alpha. METHODS:
      Thirty-six patients with chronic hepatitis B were treated with interferon alpha.
      Before, during and after the treatment, the levels of hyaluronic acid (HA), type
      III procollagen (PC-III), type IV collagen(IV-C), laminin (LN) and transforming
      growth factor beta 1 (TGF-beta 1) were measured as the markers of hepatic
      fibrosis. Needle biopsy sections of the liver taken before and at the end of IFN
      treatment were assessed and compared according to the modified histological
      activity index (HAI) and hepatic fibrosis (HF) scoring system. RESULTS: In IFN
      group, the levels of HA, PC-III, IV-C, LN, and TGF-beta 1 after treatment were
      all significantly lower than those before treatment (P<0.01). The levels of HA,
      PC-III, and TGF-beta 1 after treatment were significantly lower in IFN group than
      in control one. HAI scores decreased from 9.3+/-3.2 to 6.2 +/-2.1 and HF scores
      decreased from 7.5+/-2.2 to 5.1+/-1.8 after treatment. CONCLUSIONS: The
      improvement of hepatic fibrosis closely related to the efficacy of anti-virus.
      Interferon alpha therapy is effective for hepatic fibrosis of chronic hepatitis
      B.

PMID- 11509146
TI  - [The expression of HCV RNA polymerase in E.coli and the study of its solubility
      and antigenicity].
AB  - OBJECTIVE: To express HCV RNA polymerase and study its soluble condition and
      antigenicity. METHODS: We constructed expression vectors pQE-5B-Fl and pQE-5B-C21
      and expressed them in E.coli (M15). We analyzed their solubility in different
      conditions and purified soluble pQE-5B-C21 protein by Ni-NTA column, then
      detected its antigenicity by ELISA and western blot. RESULTS: We obtained the
      purified soluble pQE-5B-C21 protein in the induction conditions of 18 degrees C
      and the protein was proved to be of good antigenicity by ELISA and western blot.
      CONCLUSIONS: The RNA polymerase of HCV expressed in E.coli has good solubility
      and antigenicity.

PMID- 11509147
TI  - [Detection of positive-strand of transfusion transmitted virus fragment in the
      liver of cryptogenic hepatitis].
AB  - OBJECTIVE: To evaluate whether transfusion transmitted virus (TTV) replicates in
      the liver and to analyze the relationship between TTV and cryptogenic hepatitis.
      METHODS: A 3.2 kb TTV fragment was detected by nested polymerase chain reaction
      (PCR) in 31 serum samples of patients with cryptogenic hepatitis who came from a
      school where was in an outbreak area of cryptogenic hepatitis during 1996 and in
      30 healthy individuals. A hybridization/nuclease protection assay was used to
      detect positive-strand TTV fragment from the liver specimens of the 7 patients.
      RESULTS: TTV DNA was detected in serum samples from 30 of 31 (96.9%) patients and
      from 18 of 30 (60%) healthy individuals, respectively. There was significant
      difference in the prevalence of TTV infection between the two groups. Based on
      hybridization/ nuclease protection assays, we detected positive-strand TTV
      fragment in all of 7 liver specimens of the patients. CONCLUSIONS: TTV is related
      possibly to cryptogenic hepatitis. TTV can replicate in the liver. Although TTV
      only causes mild liver damage, a few patients will suffer from chronic hepatitis.

PMID- 11509148
TI  - [The growth hormone and insulin-like growth factors axis in liver failure
      patients].
AB  - OBJECTIVE: To measure circulating concentration of growth hormone (GH), insulin
      like growth factors 1 (IGF-1), and it's binding protein 1 (IGFBP1) and binding
      protein 3 (IGFBP3) in patients with sever hepatitis, and to survey the clinical
      significance of GH-IGFS axis. METHODS: The study population consisted of 18
      patients with liver failure caused by serious virous hepatitis, and of 20 normal
      volunteers. Serum concentration of GH, IGF-1, IGFBP1 and IGFBP3 was determined by
      ELISA. Liver biochemistric functions were measured by routine methods. RESULTS:
      Serum concentrations of IGF-1 and IGFBP3 were equally reduced (5.5microgram/ml +/
      6.2 microgram/ml vs 17.6 microgram/ml +/-7.0 microgram/ml, and 2.4 microgram/ml
      +/-1.3 microgram/ml vs 9.4 microgram/ml +/- 1.7microgram/ml, P<0.001,
      respectively); increased serum GH and IGFBP1 were observed (9.1ng/ml +/-12.4ng/ml
      vs 1.6ng/ml +/-2.4ng/ml, P<0.05; 67.9ng/ml+/-50.2ng/ml vs 45.8ng/ml+/-33.1ng/ml,
      P<0.01) in liver failure patients as compared with the controls. The positive
      relationship between IGF-1 and IGFBP3 (r=0.91, P<0.001) was observed. The closed
      relation between the serum IGF-1 and the prognosis of patients was also obtained.
      IGF-1<10 microgram/ml was in accord with 90% accurate rate of predicted death.
      CONCLUSIONS: The GH-IGFs axis is significantly abnormal in liver failure
      patients, suggesting the existence of GH resistance in these patients. Serum IGF
      1 may act as a predictor for their prognosis.

PMID- 11509149
TI  - [Expression of telomerase reverse transcriptase and its relationship with tumor
      suppressor gene p53 in HCC].
AB  - OBJECTIVE: To explore the expression of human telomerase reverse transcriptase
      (HTERT) and its relationship with tumor suppressor gene p53. METHODS: RNA-RNA in
      situ hybridization (ISH) technique was applied to localize the expression of
      HTERT mRNA and immunohistochemistry (IHC) was used to observe the p53 protein
      expression in 34 specimens of HCC and their corresponding non-cancerous tissues.
      Both the significance of HTERT mRNA expression in the different histopathologic
      characters and its relationship with p53 protein were investigated. RESULTS:
      HTERT was detected in tumor tissue in 30 of 34 cases (88.2%), and all the 6 cases
      of small cancer (diameter<3cm) were positive. The positive rate of HTERT mRNA was
      higher in the tumor tissues with low-differentiation, extra- or intra-hepatic
      metastasis, uncompleted fibrotic capsule and/or the non-cancerous tissue with
      chronic active lesions or positive HBsAg. Intensive signal was seen both in the
      HCC cells along the front of invasive area and in a few non-cancerous liver cells
      with dysplasia. Of all 34 HCC, p53 protein was presented in 25 cases. There was a
      correlation between the expression of HTERT mRNA and of p53 protein. The
      coincidence rate of the expression (HTERT+/p53+ and HTERT-/p53-) was 79.4%. More
      intensity of HTERT signal could be seen in the cases of positive p53. HTERT mRNA
      was not found in normal liver tissues. CONCLUSIONS: High expression of HTERT mRNA
      is proved in most cases of HCCs. HTERT expression may relate to the pathogenesis
      and the invasion of HCC. p53 may play a role in regulating the expression of
      HTERT.

PMID- 11509150
TI  - [Clinical and pathological study of autoimmune hepatopathy].
AB  - OBJECTIVE: To study the clinical and histologic characteristics of autoimmune
      hepatopathy, and to explore the diagnostic criteria and therapy. METHODS: Sixty
      two patients with autoimmune hepatopathy were studied between 1996 and 1998 to
      compare primary biliary cirrhosis (PBC) and autoimmune hepatitis (AIH) in the
      clinical symptoms, signs, laboratory findings and histologic features. RESULTS:
      PBC was 59.68% and AIH 40.32% in the autoimmune hepatopathy. The morbidity in
      middle and old aged female patients with autoimmune hepatopathy was 83.8%. The
      ratio of male and female was 1:10. Whereas, the ratio of male and female was 1:5
      in AIH patients and average age was 35 years old. Seropositive autoimmune
      antibodies were detected in 53 serum sample (PBC 85.29%; AIH 78.95%). Positive
      rates of the mitochondrial antibody and subtype-M2 were 100% for PBC. IgM
      increasing was 80% in PBC (P<0.05) and 82.35% in AIH (P<0.025). Histologic
      features in PBC group consisted of cholangitis, destruction or proliferation of
      the bile duct and inflammation within the portal tract; while in AIH group
      inflammation, necrosis and fibrosis of periportal region, the aggregation of
      lymphocytes, mononuclear cells and plasma cells in the portal tract or periportal
      area were found. CONCLUSIONS: PBC and AIH are the most common two types in the
      patients with autoimmune hepatopathy. AIH-I is more often seen clinically. AMA-M2
      is the special autoimmune antibody of PBC. The efficacy of prednisolone is better
      for AIH than PBC.

PMID- 11509151
TI  - [Genotypes of transfusion-transmitted virus].
AB  - OBJECTIVE: To investigate the genotypes of transfusion-transmitted virus (TTV) in
      South China. METHODS: One capture probe for all types of TTV from the conserved
      sequence nt2160 to nt2196 and six varied probes, heterogeneity more than 20%
      between each other for G1, G2, G3, G4, G5 and G6 type, respectively were
      synthesized. The primers coming from the conserved sequence of ORF1 were used to
      amplify TTV DNA from the serums of patients. Microplate sandwich hybridization
      ELISA technique was used to detect the genotypes of TTV in 380 hepatitis patients
      with liver damage. RESULTS: Sixty-one of 380 patients, about 16.0%, were TTV DNA
      positive, in whom 44 were genotype I (G1), 5 were G2, 10 were mixed infection of
      G1 and G2, one was G3 and one was G4. Neither G5 nor G6 has been detected. The
      rate of TTV infection in chronic hepatitis patients was equal to that in acute
      hepatitis patients. CONCLUSIONS: TTV infection is common in South China. There
      are four types of TTV. The first genotype was G1, and the second was G2. G5 or G6
      has not yet been detected. PCR microplate sandwich hybridization-ELISA has
      certain value in clinic diagnosis for its specific, sensitive and practicable
      characters.

PMID- 11509152
TI  - Does delaying placement of tympanostomy tubes have an adverse effect on
      developmental outcomes in children with persistent middle ear effusions?

PMID- 11509154
TI  - Should we use Foley catheters for preinduction cervical ripening?

PMID- 11509153
TI  - Are all beta-blockers equally effective in reducing mortality after acute
      myocardial infarction (AMI)?

PMID- 11509155
TI  - What is the best treatment for patients with severe gastroesophageal reflux
      disease (GERD)?

PMID- 11509156
TI  - Clinical inquiries. What is the best test to diagnose urinary tract stones?

PMID- 11509157
TI  - Clinical inquiries. Which patients with gastroesophageal reflux disease (GERD)
      should have esophagogastroduoudenoscopy (EGD)?

PMID- 11509158
TI  - Screening for microalbuminuria to prevent nephropathy in patients with diabetes:
      a systematic review of the evidence.
AB  - OBJECTIVE: Our goal was to evaluate whether screening patients with diabetes for
      microalbuminuria (MA) is effective according to the criteria developed by Frame
      and Carlson and those of the US Preventive Services Task Force. STUDY DESIGN: We
      searched the MEDLINE database (1966-present) and bibliographies of relevant
      articles. OUTCOMES MEASURED: We evaluated the impact of MA screening using
      published criteria for periodic health screening tests. The effect of the
      correlation between repeated tests on the accuracy of a currently recommended
      testing strategy was analyzed. RESULTS: Quantitative tests have reported
      sensitivities from 56% to 100% and specificities from 81% to 98%.
      Semiquantitative tests for MA have reported sensitivities from 51% to 100% and
      specificities from 21% to 100%. First morning, morning, or random urine sampling
      appear feasible. Assuming an individual test sensitivity of 90%, a specificity of
      90%, and a 10% prevalence of MA, the correlation between tests would have to be
      lower than 0.1 to achieve a positive predictive value for repeated testing of
      75%. CONCLUSIONS: Screening for MA meets only 4 of 6 Frame and Carlson criteria
      for evaluating screening tests. The recommended strategies to overcome diagnostic
      uncertainty by using repeated testing are based on expert opinion, are difficult
      to follow in primary care settings, do not improve diagnostic accuracy
      sufficiently, and have not been tested in a controlled trial. Although not
      advocated by the American Diabetes Association, semiquantitative MA screening
      tests using random urine sampling have acceptable accuracy but may not be
      reliable in all settings.

PMID- 11509159
TI  - Use of microalbuminuria testing in persons with type 2 diabetes: are the right
      patients being tested?
AB  - OBJECTIVE: Our goal was to determine whether adult patients with type 2 diabetes
      who had gross proteinuria or were already taking angiotensin-blocking drugs were
      screened for microalbuminuria. STUDY DESIGN: This was a retrospective cross
      sectional study. POPULATION: We included a total of 278 adult patients with type
      2 diabetes seen during 1998 and 1999 at the family medicine practices of the
      Medical University of South Carolina. OUTCOMES MEASURED: The outcomes were
      microalbuminuria testing during either 1998 or 1999 and the initiation of
      medication if the screening test result was positive. RESULTS: We found that
      patients who could derive the greatest benefit from testing (ie, those without
      preexisting proteinuria or who were not receiving an angiotensin-blocking drug)
      were no more likely to be screened for microalbuminuria than those with existing
      proteinuria (16% vs 18%, P=.84) or those who were already being treated with an
      angiotensin-converting enzyme inhibitor or angiotensin receptor blocker (16% vs
      16%, P=.83). Also, when the microalbuminuria test result was positive, only 40%
      of the patients were placed on angiotensin-blocking drugs. CONCLUSIONS: Physician
      use of microalbuminuria screening does not follow established guidelines. The
      test appears to be used for many patients who might not need to be screened, and
      it is not always used for patients who should be screened. Consideration should
      be given to other strategies to prevent nephropathy in persons with type 2
      diabetes.

PMID- 11509160
TI  - Screening for microalbuminuria.

PMID- 11509161
TI  - Improving the quality of outpatient care for older patients with diabetes:
      lessons from a comparison of rural and urban communities.
AB  - OBJECTIVE: Our goal was to compare the quality of diabetic care received by
      patients in rural and urban communities. STUDY DESIGN: We performed a
      retrospective analysis of claims data captured by the Medicare program.
      POPULATION: We included all fee-for-service Medicare patients 65 years and older
      living in the state of Washington who had 2 or more physician encounters for
      diabetes care during 1994. OUTCOME MEASURES: The outcomes were the extent to
      which patients received 3 specific recommended services: glycated hemoglobin
      determination, cholesterol measurement, and eye examination. RESULTS: A total of
      30,589 Medicare patients (8.4%) were considered to have diabetes; 29.1% lived in
      rural communities. Generalists provided most diabetic care in all locations.
      Patients living in small rural towns received almost half their outpatient care
      in larger communities. Patients living in large rural towns remote from
      metropolitan areas were more likely to have received the recommended tests than
      patients in all other groups. Patients who saw an endocrinologist at least once
      during the year were more likely to have received the recommended tests.
      CONCLUSIONS: Large rural towns may provide the best conditions for high-quality
      care: They are vibrant, rapidly growing communities that serve as regional
      referral centers and have an adequate-but not excessive-supply of both generalist
      and specialist physicians. Generalists provide most diabetic care in all
      settings, and consultation with an endocrinologist may improve adherence to
      guidelines.

PMID- 11509162
TI  - Making decisions about cancer screening when the guidelines are unclear or
      conflicting.
AB  - OBJECTIVE: Our purpose was to determine the factors involved in the cancer
      screening decisions of family physicians in situations where the clinical
      practice guidelines are unclear or conflicting as opposed to when they are clear
      and uncontroversial. STUDY DESIGN: We analyzed discussions with focus groups
      using a constant comparative approach. POPULATION: A total of 73 family
      physicians in active practice participated in 10 focus groups (1 urban group and
      1 rural group in each of 5 Canadian provinces). OUTCOME MEASURES: Our main
      outcome measures were participants' perceptions regarding cancer screening when
      the guidelines were unclear or conflicting. RESULTS: We propose a model of the
      determinants of cancer screening decision making with regard to unclear and
      conflicting guidelines. This model is rooted in the physician-patient
      relationship, and is an interactive process influenced by patient factors
      (anxiety, expectations, and family history) and physician factors (perception of
      guidelines, clinical practice experience, influence of colleagues, distinction
      between the screening styles of specialists and family physicians, and the amount
      of time and financial costs involved in performing the maneuver). CONCLUSIONS:
      Our model is unique, because it is embedded in the physician-patient
      relationship. Ultimately, a modified model could be used to design interventions
      to assist with the implementation of preventive services guidelines.

PMID- 11509163
TI  - Direct observation of smoking cessation activities in primary care practice.
AB  - OBJECTIVE: Our goals were to determine how often family physicians incorporate
      smoking cessation efforts into routine office visits and to examine the effect of
      patient, physician, and office characteristics on the frequency of these efforts.
      STUDY DESIGN: Data was gathered using direct observation of physician-patient
      encounters, a survey of physicians, and an on-site examination of office systems
      for supporting smoking cessation. POPULATION: We included patients seen for
      routine office visits in 38 primary care physician practices. OUTCOMES MEASURED:
      The frequency of tobacco discussions among all patients, the extent of these
      discussions among smokers, and the presence of tobacco-related systems and
      policies in physicians' offices were measured. RESULTS: Tobacco was discussed
      during 633 of 2963 encounters (21%; range among practices = 0%-90%). Discussion
      of tobacco was more common in the 58% of practices that had standard forms for
      recording smoking status (26% vs 16%; P=.01). Tobacco discussions were more
      common during new patient visits but occurred less often with older patients and
      among physicians in practice more than 10 years. Of 244 smokers identified,
      physicians provided assistance with smoking cessation for 38% (range among
      practices = 0%-100%). Bupropion and nicotine-replacement therapy were discussed
      with smokers in 31% and 17% of encounters, respectively. Although 68% of offices
      had smoking cessation materials for patients, few recorded tobacco use in the
      "vital signs" section of the patient history or assigned smoking-related tasks to
      nonphysician personnel. CONCLUSIONS: Smoking cessation practices vary widely in
      primary care offices. Strategies are needed to assist physicians with
      incorporating systematic approaches to maximize smoking cessation rates.

PMID- 11509164
TI  - Ergogenic supplements and health risk behaviors.
AB  - OBJECTIVE: Our goals were to determine the prevalence of ergogenic supplement use
      in a young healthy population and to examine the extent to which supplement use
      is associated with specific health risk behaviors. STUDY DESIGN: We performed a
      cross-sectional survey. POPULATION: Individuals entering military service for
      enlisted training were included. OUTCOMES MEASURED: We recorded previous use of
      any nutritional ergogenic supplements and self-reported health risk behaviors.
      RESULTS: Of 550 eligible participants, 499 completed the survey (91% response
      rate). Individuals who used ergogenic supplements were more likely to drink
      alcohol (adjusted odds ratio [AOR]=1.8; 95% confidence interval [CI], 1.1-3.1),
      more likely to drink heavily (AOR=2.4; 95% CI, 1.5-3.9), more likely to ride in a
      vehicle with someone who had been drinking (AOR=2.2; 95% CI, 1.3-3.6), more
      likely to drive after drinking (AOR=2.4; 95% CI, 1.3-4.4), and more likely to
      have been in a physical fight (AOR=1.9; 95% CI, 1.0-3.5), compared with those who
      had not used supplements. Men were more likely to use supplements than women (P
      &lt.001). There were no differences in patterns of supplement use according to
      age or body mass index. CONCLUSIONS: Our study indicates an association between
      individuals who use ergogenic nutritional supplements and specific health risk
      behaviors. This represents an important opportunity for preventive counseling.

PMID- 11509165
TI  - A comprehensive investigation of barriers to adult immunization: a methods paper.
AB  - OBJECTIVE: Immunization rates for influenza and pneumococcal vaccines among the
      elderly (especially minority elderly) are below desired levels. We sought to
      answer 4 questions: (1) What factors explain most missed immunizations? (2) How
      are patient beliefs and practices regarding adult immunization affected by racial
      or cultural factors? (3) How are immunizations and patient beliefs affected by
      physician, organizational, and operational factors? and (4) Based on the
      relationships identified, can typologies be created that foster the tailoring of
      interventions to improve immunization rates? STUDY DESIGN: A multidisciplinary
      team chose the PRECEDE-PROCEED framework, the Awareness-to-Adherence model of
      clinician response to guidelines, and the Triandis model of consumer decision
      making as the best models to assess barriers to and facilitators of immunization.
      Our data collection methods included focus groups, face-to-face and telephone
      interviews, self-administered surveys, site visits, participant observation, and
      medical record review. POPULATION: To encounter a broad spectrum of patients,
      facilities, systems, and interventions, we sampled from 4 strata: inner-city
      neighborhood health centers, clinics in Veterans Administration facilities, rural
      practices in a network, and urban/suburban practices in a network. In stage 1, a
      stratified random cluster sample of 60 primary care clinicians was selected, 15
      in each of the strata. In stage 2, a random sample of 15 patients was selected
      from each clinician's list of patients, aiming for 900 total interviews.
      CONCLUSIONS: This multicomponent approach is well suited to identifying barriers
      to and facilitators of adult immunizations among a variety of populations,
      including the disadvantaged.

PMID- 11509166
TI  - The diagnosis of essential and secondary hypertension in adults.

PMID- 11509167
TI  - Single question screening for problem drinking.

PMID- 11509168
TI  - Are antibiotics effective in the treatment of acute sinusitis in children and
      adolescents?

PMID- 11509169
TI  - What is the best treatment for patients with symptomatic mild-to-moderate hallux
      valgus (bunions)?

PMID- 11509170
TI  - Is fluvoxamine safe and effective for treating anxiety disorders in children?

PMID- 11509171
TI  - Is ginger root effective for decreasing the severity of nausea and vomiting in
      early pregnancy?

PMID- 11509172
TI  - Dendritic cells: specialized and regulated antigen processing machines.

PMID- 11509173
TI  - Dendritic cell subsets and lineages, and their functions in innate and adaptive
      immunity.

PMID- 11509174
TI  - Regulation of T cell immunity by dendritic cells.

PMID- 11509175
TI  - The host-pathogen interaction: new themes from dendritic cell biology.

PMID- 11509176
TI  - Dendritic cells as vectors for therapy.

PMID- 11509177
TI  - Telomere dysfunction increases mutation rate and genomic instability.
AB  - The increased tumor incidence in telomerase null mice suggests that telomere
      dysfunction induces genetic instability. To test this directly, we examined
      mutation rate in the absence of telomerase in S. cerevisiae. The mutation rate in
      the CAN1 gene increased 10- to 100-fold in est1Delta strains as telomeres became
      dysfunctional. This increased mutation rate resulted from an increased frequency
      of terminal deletions. Chromosome fusions were recovered from est1Delta strains,
      suggesting that the terminal deletions may occur by a breakage-fusion-bridge type
      mechanism. At one locus, chromosomes with terminal deletions gained a new
      telomere through a Rad52p-dependent, Rad51p-independent process consistent with
      break-induced replication. At a second locus, more complicated rearrangements
      involving multiple chromosomes were seen. These data suggest that telomerase can
      inhibit chromosomal instability.

PMID- 11509178
TI  - Replication from oriP of Epstein-Barr virus requires human ORC and is inhibited
      by geminin.
AB  - A hypomorphic mutation made in the ORC2 gene of a human cancer cell line through
      homologous recombination decreased Orc2 protein levels by 90%. The G1 phase of
      the cell cycle was prolonged, but there was no effect on the utilization of
      either the c-Myc or beta-globin cellular origins of replication. Cells carrying
      this mutation failed to support the replication of a plasmid bearing the oriP
      replicator of Epstein Barr virus (EBV), and this defect was rescued by
      reintroduction of Orc2. Orc2 specifically associates with oriP in cells, most
      likely through its interaction with EBNA1. Geminin, an inhibitor of the mammalian
      replication initiation complex, inhibits replication from oriP. Therefore, ORC
      and the human replication initiation apparatus is required for replication from a
      viral origin of replication.

PMID- 11509179
TI  - The p400 complex is an essential E1A transformation target.
AB  - Here, we report the identification of a new E1A binding protein complex that is
      essential for E1A-mediated transformation. Its core component is a SWI2/SNF2
      related, 400 kDa protein (p400). Other components include the myc- and p/CAF
      associated cofactor, TRRAP/PAF400, the DNA helicases TAP54alpha/beta, actin-like
      proteins, and the human homolog of the Drosophila Enhancer of Polycomb protein.
      An E1A mutant, defective in p400 binding, is also defective in transformation.
      Certain p400 fragments partially rescued this phenotype, underscoring the role of
      E1A-p400 complex formation in the E1A transforming process. Furthermore, E1A and
      c-myc each alter the subunit composition of p400 complexes, implying that
      physiological p400 complex formation contributes to transformation suppression.

PMID- 11509180
TI  - Regulation of CSF1 promoter by the SWI/SNF-like BAF complex.
AB  - The mammalian BAF complex regulates gene expression by modifying chromatin
      structure. In this report, we identify 80 genes activated and 2 genes repressed
      by the BAF complex in SW-13 cells. We find that prior binding of NFI/CTF to the
      NFI/CTF binding site in CSF1 promoter is required for the recruitment of the BAF
      complex and the BAF-dependent activation of the promoter. Furthermore, the
      activation of the CSF1 promoter requires Z-DNA-forming sequences that are
      converted to Z-DNA structure upon activation by the BAF complex. The BAF complex
      facilitates Z-DNA formation in a nucleosomal template in vitro. We propose a
      model in which the BAF complex promotes Z-DNA formation which, in turn,
      stabilizes the open chromatin structure at the CSF1 promoter.

PMID- 11509181
TI  - Two splice variants of the Wilms' tumor 1 gene have distinct functions during sex
      determination and nephron formation.
AB  - Alternative splicing of Wt1 results in the insertion or omission of the three
      amino acids KTS between zinc fingers 3 and 4. In vitro experiments suggest
      distinct molecular functions for + and -KTS isoforms. We have generated mouse
      strains in which specific isoforms have been removed. Heterozygous mice with a
      reduction of +KTS levels develop glomerulosclerosis and represent a model for
      Frasier syndrome. Homozygous mutants of both strains die after birth due to
      kidney defects. Strikingly, mice lacking +KTS isoforms show a complete XY sex
      reversal due to a dramatic reduction of Sry expression levels. Our data
      demonstrate distinct functions for the two splice variants and place the +KTS
      variants as important regulators for Sry in the sex determination pathway.

PMID- 11509182
TI  - Structure of bovine mitochondrial F(1)-ATPase with nucleotide bound to all three
      catalytic sites: implications for the mechanism of rotary catalysis.
AB  - The crystal structure of a novel aluminium fluoride inhibited form of bovine
      mitochondrial F(1)-ATPase has been determined at 2 A resolution. In contrast to
      all previously determined structures of the bovine enzyme, all three catalytic
      sites are occupied by nucleotide. The subunit that did not bind nucleotide in
      previous structures binds ADP and sulfate (mimicking phosphate), and adopts a
      "half-closed" conformation. This structure probably represents the
      posthydrolysis, pre-product release step on the catalytic pathway. A catalytic
      scheme for hydrolysis (and synthesis) at physiological rates and a mechanism for
      the ATP-driven rotation of the gamma subunit are proposed based on the crystal
      structures of the bovine enzyme.

PMID- 11509183
TI  - Gibberellins signal nuclear import of PHOR1, a photoperiod-responsive protein
      with homology to Drosophila armadillo.
AB  - S. tuberosum ssp. andigena potato plants require short days (SD) for
      tuberization. We have isolated PHOR1 (photoperiod-responsive 1), which shows
      upregulated expression in induced leaves (SD). PHOR1 encodes an arm repeat
      protein with homology to the Drosophila segment polarity protein armadillo.
      Antisense inhibition of PHOR1 produces a semidwarf phenotype similar to that of
      GA-deficient plants, and the antisense lines show reduced GA responsiveness
      combined with a higher endogenous GA content than wild-type plants. Feedback
      regulation of GA biosynthetic genes is also altered in these lines. Conversely,
      transgenic lines overexpressing PHOR1 show an enhanced response to GA. GA
      application induces rapid migration of PHOR1-GFP protein to the nucleus. Thus,
      PHOR1 appears to be a general component of GA signaling pathways that relocalizes
      to the nucleus in the presence of GA.

PMID- 11509184
TI  - The Partner of Inscuteable/Discs-large complex is required to establish planar
      polarity during asymmetric cell division in Drosophila.
AB  - Frizzled (Fz) signaling regulates cell polarity in both vertebrates and
      invertebrates. In Drosophila, Fz orients the asymmetric division of the sensory
      organ precursor cell (pI) along the antero-posterior axis of the notum. Planar
      polarization involves a remodeling of the apical-basal polarity of the pI cell.
      The Discs-large (Dlg) and Partner of Inscuteable (Pins) proteins accumulate at
      the anterior cortex, while Bazooka (Baz) relocalizes to the posterior cortex. Dlg
      interacts directly with Pins and regulates the localization of Pins and Baz. Pins
      acts with Fz to localize Baz posteriorly, but Baz is not required to localize
      Pins anteriorly. Finally, Baz and the Dlg/Pins complex are required for the
      asymmetric localization of Numb. Thus, the Dlg/Pins complex responds to Fz
      signaling to establish planar asymmetry in the pI cell.

PMID- 11509185
TI  - A polymorphic genomic duplication on human chromosome 15 is a susceptibility
      factor for panic and phobic disorders.
AB  - Anxiety disorders are complex and common psychiatric illnesses associated with
      considerable morbidity and social cost. We have studied the molecular basis of
      the cooccurrence of panic and phobic disorders with joint laxity. We have
      identified an interstitial duplication of human chromosome 15q24-26 (named
      DUP25), which is significantly associated with panic/agoraphobia/social
      phobia/joint laxity in families, and with panic disorder in nonfamilial cases.
      Mosaicism, different forms of DUP25 within the same family, and absence of
      segregation of 15q24-26 markers with DUP25 and the psychiatric phenotypes suggest
      a non-Mendelian mechanism of disease-causing mutation. We propose that DUP25,
      which is present in 7% control subjects, is a susceptibility factor for a
      clinical phenotype that includes panic and phobic disorders and joint laxity.

PMID- 11509186
TI  - Mammalian sweet taste receptors.
AB  - The sense of taste provides animals with valuable information about the quality
      and nutritional value of food. Previously, we identified a large family of
      mammalian taste receptors involved in bitter taste perception (the T2Rs). We now
      report the characterization of mammalian sweet taste receptors. First, transgenic
      rescue experiments prove that the Sac locus encodes T1R3, a member of the T1R
      family of candidate taste receptors. Second, using a heterologous expression
      system, we demonstrate that T1R2 and T1R3 combine to function as a sweet
      receptor, recognizing sweet-tasting molecules as diverse as sucrose, saccharin,
      dulcin, and acesulfame-K. Finally, we present a detailed analysis of the patterns
      of expression of T1Rs and T2Rs, thus providing a view of the representation of
      sweet and bitter taste at the periphery.

PMID- 11509187
TI  - Estrous cycle modulation of nociceptive behaviors elicited by electrical
      stimulation and formalin.
AB  - The impact of circulating ovarian hormones on nociceptive behaviors elicited by
      phasic and tonic stimuli was evaluated in rats using two behavioral tests: an
      operant escape task and the formalin test. The operant escape task was structured
      to separately evaluate hindlimb flexion reflexes, the latency of escape, and the
      amplitude of peak vocalization to a series of phasic electrocutaneous stimuli
      (0.05-0.8 mA), whereas the formalin test evaluated nociceptive behaviors elicited
      by tonic stimulation following a subcutaneous injection of dilute formalin (1%).
      Hindlimb reflex amplitude, escape latency, and peak vocalization varied across
      the estrous cycle, such that rats were most sensitive to electrical stimuli
      during proestrus (reflex and escape latency) and diestrus (vocalization).
      Furthermore, morphine-induced (3 mg/kg sc) attenuation of hindlimb reflex
      amplitude was sensitive to estrous cycling. During proestrus, morphine produced
      less attenuation of hindlimb reflex amplitude than during nonproestrus phases.
      However, estrous cycling did not alter nociceptive behaviors elicited by 1%
      formalin. These data support the notion that circulating ovarian hormones may
      differentially modulate behaviors associated with phasic and tonic pain.

PMID- 11509188
TI  - How REM sleep deprivation and amantadine affects male rat sexual behavior.
AB  - There are conflicting findings about the sexual effects of REM sleep deprivation
      (REMd). Otherwise, several studies show a dopaminergic hypersensitivity after
      REMd. The effect of REMd and amantadine (AMA) was studied for standard measures
      and temporal patterning in the first experiment, in four groups: normal with
      vehicle, normal with AMA (5.0 and 10 mg/kg), REMd with vehicle and REMd with AMA
      (5.0 and 10.0 mg/kg). REMd reduced mount latency (ML), intromission latency (IL)
      and mount number (MN) and increased copulatory efficiency (CE) and hit rate
      factor. REMd also reduced the mount bout number (MBN) and increased the sexual
      interaction (mount bout time, MBT) among male and female during copula. AMA
      stimulates initiation and hit rate factors and accelerates the temporal
      patterning of sexual behavior, evoking fewer and quicker mount bouts. In the
      experiments with combination of REMd and AMA administration, AMA did not increase
      behavior effects evoked by REM deprivation, probably due to a top or a bottom
      effect, depending on the measures considered. A second experiment studied the
      effects of AMA (1.25 to 5.0 mg/kg) and REMd on the sexual reflexes of
      nonimmobilized male rats. REMd enhanced the AMA effects upon the seminal emission
      reflex, but inhibited the penile erection reflex elicited by 1.25 mg/kg of AMA.
      Curiously, our results showed that REMd, like AMA, a dopaminergic agonist, causes
      similar effects of sexual behavior in the male rat, particularly those related to
      arousal mechanism and hit rate factor. The results are discussed and the effects
      of REMd probably involve dopaminergic hypersensitivity and increased sexual
      motivational response.

PMID- 11509189
TI  - Behavioral and biochemical effects of L-tryptophan and buspirone in a model of
      cerebellar atrophy.
AB  - The Lurcher mutant mouse can be considered an adequate model of autosomal
      dominant spinocerebellar atrophy because of the severe degeneration of its
      cerebellar cortex and inferior olive. The purpose of this study was to determine
      whether the motor coordination deficits of Lurcher mutants could be improved
      after chronic administration of the serotonin (5-hydroxytryptamine; 5-HT)
      precursor, L-tryptophan, or of the 5-HT(1A) agonist, buspirone. During these
      treatments, the mice were submitted to behavioral evaluations using the coat
      hanger and the rotorod tests, as well as an inclined screen and a vertical grid
      test. At the end of treatments, 5-HT and 5-hydroxindole-3-acetic acid (5-HIAA)
      were measured in six brain regions. On the coat hanger test, administration of L
      tryptophan accelerated movements along the horizontal bar by 44%, while buspirone
      increased the time spent on the apparatus by 11%. Neither drug had an effect on
      climbing ability or on the time spent on a rotating beam. Administration of L
      tryptophan increased 5-HIAA levels in frontal cortex, neostriatum, thalamus,
      brainstem, cerebellum and spinal cord, but elevated 5-HT only in neostriatum,
      brainstem and cerebellum. In contrast, buspirone led to 5-HT increases in
      cerebellum and augmented 5-HIAA in the spinal cord. The modest test-specific
      improvements are consistent with some of the clinical data concerning 5-HT
      pharmacotherapy in patients suffering from cerebellar atrophy.

PMID- 11509191
TI  - Effect of the Ginkgo biloba extract, EGb 761, on memory formation in day-old
      chicks.
AB  - Previous studies indicate that the Ginkgo biloba extract, EGb 761, has a
      facilitative effect on deficient memory. The temporal parameters of this effect,
      however, have not been clearly defined or distinguished from the effect on normal
      memory. The aim in the current study was to investigate the effects of EGb 761 on
      memory using a well-controlled animal model. Day-old chicks were trained on
      either a weakly or strongly reinforced version of a passive avoidance task. Long
      term memory formation of the weakly reinforced version of the task was improved
      significantly by EGb 761 (3 mg/ml) when administered between 10 and 30 min after
      training. However, the same dose of EGb 761 impaired retention when administered
      prior to strongly reinforced training. These data provide convincing evidence
      that posttraining administration of EGb 761 initiates long-term memory in chicks
      with only short-term memory, but that the same dose-administered pretraining can
      be deleterious for normal retention. This dual effect has important implications
      for the clinical use of Ginkgo biloba extracts.

PMID- 11509190
TI  - Antiemetic efficacy of smoked marijuana: subjective and behavioral effects on
      nausea induced by syrup of ipecac.
AB  - Although the public debate about the legalization of marijuana has continued for
      as long as 25 years, few controlled studies have been conducted to assess its
      potential medical benefits. The present study examined the antiemetic effect of
      smoked marijuana cigarettes (8.4 and 16.9 mg Delta(9)-tetrahydrocannabinol [THC])
      compared to a highly potent antiemetic drug, ondansetron (8 mg) in 13 healthy
      volunteers. Nausea and emesis were induced by syrup of ipecac. Marijuana
      significantly reduced ratings of "queasiness" and slightly reduced the incidence
      of vomiting compared to placebo. Ondansetron completely eliminated the emetic
      effects of ipecac. These findings support and extend previous results, indicating
      that smoked marijuana reduces feelings of nausea and also reduces emesis in this
      model. However, its effects are very modest relative to ondansetron, and the
      psychoactive effects of marijuana are likely to limit its clinical usefulness in
      the general population.

PMID- 11509192
TI  - Chronic corticosterone treatment alters sensory gating in C3H mice.
AB  - Two methods of evaluating inhibitory sensory processing are prepulse inhibition
      of acoustic startle (PPI) and gating of auditory evoked potentials. Studies using
      both methods suggest nicotinic acetylcholinergic receptor modulation of gating,
      specifically the alpha-bungarotoxin (alpha-BTX) binding site (alpha7 receptor
      subtype). However, recent assessment of alpha7 null mutant mice failed to
      demonstrate any effect of the loss of this receptor in either gating paradigm. An
      alternate approach to assessing the effects of the alpha7 receptor is to reduce
      its numbers in mature inbred mice, thus, avoiding the twin problems of background
      and developmental compensation inherent in null mutant mouse studies. Numerous
      studies have shown that chronic corticosterone (CCS) treatment selectively
      reduces alpha-BTX binding sites. C3H mice were adrenalectomized and implanted
      with corticosterone or cholesterol (control) pellets. After 8 days, they were
      tested in one of the gating paradigms. PPI and auditory gating were significantly
      diminished in corticosterone-treated mice concomitant with a reduction in alpha
      BTX binding in several brain regions. Cholesterol-treated mice had no change in
      either paradigm. Nicotine treatment (1 mg/kg) produced significant improvement in
      both paradigms in corticosterone-treated mice. These data agree with previous
      pharmacological studies suggesting modulation of gating occurs through a
      nicotinic receptor.

PMID- 11509193
TI  - Different effects of anxiolytic agents, diazepam and 5-HT(1A) agonist
      tandospirone, on hippocampal long-term potentiation in vivo.
AB  - Benzodiazepines and 5-HT(1A) agonists have been widely used as anxiolytic agents.
      Some clinical reports document that 5-HT(1A) agonists induce memory impairment to
      a lesser degree than diazepam. In the present study, we compared the effects of
      diazepam and 5-HT(1A) agonist, tandospirone, on hippocampal long-term
      potentiation (LTP) in Schaffer collateral-CA1, mossy fiber-CA3 and perforant path
      dentate gyrus synapses. In the diazepam-injected group, the reduction in LTP was
      observed in all three types of synapses, although the effective dose differed
      among these. In the tandospirone-injected group, no reduction in LTP was observed
      except in Schaffer-CA1 synapses. In addition, population spike amplitude was
      potentiated by tandospirone in mossy fiber-CA3 synapses in a dose-dependent
      manner. Thus, there was a discrepancy in the effects on hippocampal LTP between
      diazepam and tandospirone, possibly reflecting the reported clinical properties
      of these drugs, in that 5-HT(1A) partial agonists do not affect learning and
      memory, whereas diazepam impairs memory function.

PMID- 11509194
TI  - D1 or D2 antagonism in nucleus accumbens core or dorsomedial shell suppresses
      lever pressing for food but leads to compensatory increases in chow consumption.
AB  - Although interference with dopamine (DA) systems can suppress lever pressing for
      food reinforcement, it is not clear whether this effect occurs because of a
      general disruption of food motivation. One way of assessing this has been a
      choice procedure in which a rat responds on an fixed ratio 5 (FR5) schedule for
      preferred Bioserve pellets while a less preferred lab chow is concurrently
      available in the operant chamber. Untreated rats consume little of the chow,
      preferring to respond for the Bioserve pellets. Previous studies have shown that
      depleting DA in the accumbens substantially decreased lever pressing while
      increasing chow consumption. In the present study, low doses (0.0625-1.0 microg)
      of the D1 antagonist SCH 23390 or the D2 antagonist raclopride were injected into
      the either the core or shell subregions of nucleus accumbens, and rats were
      tested on the concurrent lever pressing/feeding task. Analysis of the dose
      response curves showed that injections of SCH 23390 into the core were more
      potent than injections into the shell for suppressing lever pressing (i.e., the
      ED(50) was lower in the core). Nevertheless, injections of either drug into
      either site suppressed lever pressing and increased intake of the concurrently
      available chow. Across both drugs and at both sites, the amount of chow consumed
      was negatively correlated with the total number of responses. Neither drug
      significantly increased response duration, suggesting that accumbens DA
      antagonism did not produce the type of motor impairment that leads to severe
      alterations in the form of lever pressing. In summary, the blockade of D1 or D2
      receptors in nucleus accumbens core or shell decreased lever pressing for food
      reinforcers, but rats remained directed toward the acquisition and consumption of
      food. These results indicate that accumbens D1 antagonism does not decrease lever
      pressing because of a general reduction in food motivation. Nevertheless,
      interference with accumbens DA does appear to set constraints upon which
      responses are selected for obtaining food, and may impair the ability of animals
      to overcome work-related response costs in order to obtain food.

PMID- 11509195
TI  - Ambulation-promoting effect of peppermint oil and identification of its active
      constituents.
AB  - Various plant-derived essential oils (EOs) have traditionally been used in the
      treatment of mental disorders, despite a lack of scientific evidence. In a
      previous study, we demonstrated that certain EOs possess behavioral effects, a
      finding that supports our original hypotheses that EOs possess psychoactive
      actions. The present study was conducted in order to obtain further evidence to
      support our hypothesis. Peppermint oil, a type of EO, is believed to be effective
      for treating mental fatigue. When the oil was administered intraperitoneally to
      ICR mice, the ambulatory activity of mice increased dramatically. We identified
      alpha-pinene, beta-pinene, (R)-(+)-limonene, 1,8-cineol, isomenthone, menthone,
      menthol, (R)-(+)-pulegone, menthyl acetate and caryophyllene as constituent
      elements of peppermint oil by GC-MS analysis. We then examined the effect of each
      constituent element of peppermint oil on ambulatory activity in mice.
      Intraperitoneal administration of 1,8-cineol, menthone, isomenthone, menthol, (R)
      (+)-pulegone, menthyl acetate and caryophyllene significantly increased
      ambulatory activity in mice, suggesting that these chemicals are the behaviorally
      active elements of peppermint oil. Intravenous administration of these substances
      to mice induced a significant increase in ambulatory activity at much lower
      doses. The present study provides further evidence demonstrating that EOs possess
      pharmacological actions on behavior. In addition, our finding revealed that the
      action of peppermint oil comes from its constituent elements.

PMID- 11509196
TI  - Septal GABAergic and hippocampal cholinergic systems modulate anxiety in the plus
      maze and shock-probe tests.
AB  - According to Gray [The neuropsychology of anxiety: an inquiry into the function
      of the septo-hippocampal system. Oxford: Oxford Univ. Press, 1982; Neural
      systems, emotion and personality. In: Madden VJ, editor. Neurobiology of
      learning, emotion, and affect. New York: Raven Press, 1991. p. 273-306.] the
      septum and hippocampus act in concert to control anxiety. In the present study we
      examined the roles of these structures in two animal models of anxiety: the
      elevated plus-maze and the shock-probe burying tests. We found that
      microinfusions (20 ng/0.4 microl) of the GABA(A) agonist muscimol into either the
      lateral or the medial septum increased rats' open-arm exploration in the plus
      maze test, and decreased their burying behavior in the shock-probe test. We also
      found that infusions of the acetylcholinesterase inhibitor physostigmine (10
      microg/microl) into the dorsal hippocampus, like intraseptal muscimol (20 ng/0.4
      microl), increased open-arm exploration in the plus-maze test, and decreased
      burying behavior in the shock-probe test. Although combined infusions of
      intraseptal muscimol and intrahippocampal physostigmine did not increase the
      magnitude of anxiolysis, this may have been due to "ceiling" effects. Overall,
      the results confirm that septal GABAergic and hippocampal cholinergic systems are
      both involved in the modulation of anxiety.

PMID- 11509197
TI  - Long-term exposures to higher environmental temperature and body temperature:
      effect of chlorpromazine in relation to hypothalamic GABA.
AB  - Treatment with a single dose of chlorpromazine (CPZ; 1 mg/kg, ip) at room
      temperature (28 degrees +/-0.5 degrees C) significantly reduced body temperature
      by its anticholinergic action. Long-term exposures to higher environmental
      temperature (40 degrees +/-0.5 degrees C, 2 h/day, for 30 consecutive days)
      increased body temperature significantly by reduction of hypothalamic GABAergic
      activity, but this increase in body temperature was attenuated from that observed
      with a single exposure to higher environmental temperature (40 degrees C for 2
      h). Treatment with a single dose of CPZ on the last day of 30 consecutive days of
      exposures to higher environmental temperature increased body temperature of rats
      more than that observed with long-term exposures to higher environmental
      temperature possibly due to (i) reduction of hypothalamic GABAergic activity,
      (ii) heat dissipation and (iii) reverse-anticholinergic action of CPZ at higher
      environmental temperature.

PMID- 11509198
TI  - Iron deficiency decreases dopamine D1 and D2 receptors in rat brain.
AB  - Iron deficiency (ID) in early life is known to alter neurological development and
      functioning, but data regarding specific effects on dopamine biology are lacking.
      The objective of this study was to determine the extent of functional alterations
      in dopamine receptors in two dopaminergic tracts in young, growing, iron
      deficient rats. Forty male and 40 female weanling Sprague-Dawley rats were fed
      either an iron-deficient (ID) diet or control (CN) diet for 6 weeks. ID decreased
      densities of D(1) and D(2) receptors in the caudate-putamen and decreased D(2)
      receptor densities in the nucleus accumbens. There were no apparent effects of ID
      on the affinities for the ligands in either receptor in several brain regions. In
      situ hybridization studies for both dopamine receptors revealed no significant
      effect of ID on mRNA expression for either receptor. Iron-deficient rats had a
      significantly higher ED(50) for raclopride-induced hypolocomotion in male and
      female rats compared to control rats of each sex. The loss of iron in the
      striatum due to dietary ID was significantly correlated with the decrease in D(2)
      receptor density; however, this relationship was not apparent in other brain
      regions. These experiments thus demonstrate abnormal dopamine receptor density
      and functioning in several brain regions that are related to brain regional iron
      loss. Importantly, the impact of ID on dopamine was more pronounced in males than
      females, demonstrating sex-related different sensitivities to nutrient
      deprivation.

PMID- 11509199
TI  - On the mechanism of tolerance to morphine-induced Straub tail reaction in mice.
AB  - The effect of 5-HT and opioid receptor antagonists on morphine-induced Straub
      tail was studied in mice. Straub tail behavior was induced by subcutaneous
      administration of different doses (20, 30, and 40 mg/kg) of morphine
      hydrochloride to mice. The effect of morphine was dose-dependent. Maximum
      response was obtained with 40 mg/kg of the drug. The response induced by morphine
      (20 and 40 mg/kg) was decreased by different doses of intraperitoneal injection
      of naloxone (1 and 2 mg/kg) or methysergide, mianserin, and ritanserin (1 and 2
      mg/kg). The effect of morphine (40 mg/kg) was also reduced by
      intracerebroventricular injection of naloxone (0.4-0.8 microg/animal) or
      mianserin (2 and 4 microg/animal). Different groups of mice received one daily
      dose (50 mg/kg sc) of morphine sulfate for 3 days to develop tolerance to
      morphine. The Straub tail reaction induced by morphine hydrochloride (40 mg/kg)
      was tested on the fourth day. Naloxone injection (1 and 2 mg/kg ip) on Day 3 (1 h
      after morphine sulfate injection) or on Day 4 (1 h before test dose of morphine
      hydrochloride), decreased tolerance induced to morphine. Methysergide, mianserin,
      or ritanserin (intraperitoneal) on Days 2 and 3 (1 h after morphine sulfate
      injection) or on Day 4 (1 h before test dose of morphine hydrochloride), also
      decreased tolerance induced to morphine. Intracerebroventricular injection of
      either naloxone or mianserin also reduced tolerance to morphine. It is concluded
      that 5-HT(2) and opioid receptor mechanisms are involved in morphine-induced
      Straub tail reaction and tolerance induced to morphine also may be mediated
      through these receptors.

PMID- 11509200
TI  - The effect of dopamine receptor blockade on motor behavior in Aplysia
      californica.
AB  - The mammalian D1- and D2-like receptor blockers SCH-23390 and raclopride were
      used to block receptors in Aplysia californica, and the effect on reflexes and
      escape behavior was examined. Four groups of 20 young adults were each injected
      with SCH-23390, raclopride, SCH-23390+raclopride, or seawater. The drug (0.0125
      mg/g of body weight) was injected 2 mm anterior to the parapodia. After the
      injection of either SCH-23390 or SCH-23390+raclopride, there was a significant
      increase in parapodia opening (P<.001), siphon withdrawal (P<.05), and galloping
      following tail pinch (P<.01) compared to raclopride-injected or control animals.
      The data showed that blockade of receptors by SCH-23390, but not raclopride,
      produced significant changes in motor behavior in A. californica.

PMID- 11509201
TI  - Hippocampus and locus coeruleus activity on rats chronically treated with
      diazepam.
AB  - The neural mechanisms underlying benzodiazepine (BZD) dependence remain
      equivocal. The present studies tested the hypothesis that similar neural
      circuitry might be involved in the effects of chronic 7-chloro-1-methyl-5-phenyl
      3H-1,4-benzodiazepine-2(1H)-one, diazepam (DZ, Roche), administration and
      withdrawal. The results of our study showed an increased hippocampal synaptic
      plasticity in slices from rats chronically treated with DZ (5 mg/kg/18 days),
      assessed as a decrease of the threshold in the stimulation rate for long-term
      potentiation (LTP) elicitation. Rats with the same schedule of DZ administration
      but without signs of withdrawal behaved similarly to vehicle-treated ones (VEH),
      in the threshold to induce LTP. Furthermore, the activity of locus coeruleus (LC)
      norepinephrine (NE) neurons in rats tested 24 h after the last DZ injection
      showed a significant increase. On the other hand, rats that after chronic DZ
      administration did not develop signs of withdrawal and exhibited a similar
      pattern of discharge on LC-NE nucleus compared with their controls. We conclude
      that chronic DZ administration enhances both hippocampal synaptic plasticity and
      activity of LC-NE neurons. This neural system could be the biological substrate
      underlying the behavioral alterations accompanying chronic DZ administration and
      withdrawal.

PMID- 11509202
TI  - Nootropic and anxiolytic activity of saponins of Albizzia lebbeck leaves.
AB  - The effect of saponin containing, n-butanolic fraction (BF), extracted from dried
      leaves of Albizzia lebbeck, was studied on cognitive behavior and anxiety in
      albino mice. The elevated plus maze was used for assessment of both nootropic and
      anxiolytic activity. The nootropic activity was evaluated by recording the effect
      of BF (0, 10, 25, and 50 mg/kg) on the transfer latency, whereas anxiolytic
      activity was assessed by studying its effect on the duration of occupancy in the
      closed arm. Results showed significant improvement in the retention ability of
      the normal and amnesic mice as compared to their respective controls. Animals
      treated with BF (25 mg/kg) spent more time in the open arm in a dose-dependent
      manner. The BF was without any significant effect on motor coordination. However,
      it significantly inhibited passivity and hypothermia induced by baclofen (10
      mg/kg), a GABA(B) agonist. The data emanated in the present study suggests
      involvement of gamma-aminobutyric acid (GABA) in the nootropic and anxiolytic
      activity of saponins obtained from A. lebbeck.

PMID- 11509203
TI  - Involvement of the hypothalamus-pituitary-adrenal axis in antidepressant activity
      of corticotropin-releasing factor subtype 1 receptor antagonists in the rat
      learned helplessness test.
AB  - Effects of corticotropin-releasing factor (CRF) subtype 1 receptor antagonists on
      learned helplessness (LH) were examined in rats. Repeated administration of
      CRF(1) receptor antagonists, CRA1000 (3 mg/kg, po) and CP-154,526 (10 mg/kg, po),
      and tricyclic antidepressant, imipramine (10 mg/kg, po), for 8 days significantly
      decreased the number of escape failures in LH. On the other hand, acute treatment
      of adrenocorticotropin (ACTH) abolished the decreased number of escape failures
      seen with imipramine. Likewise, in this ACTH model, the CRA1000- and CP-154,526
      induced decrease in the number of escape failures was no longer observed. The
      CRF(1) receptor is apparently involved in the produced escape failures in LH, and
      the attenuated LH seen with CRF(1) receptor antagonists was abolished by ACTH. It
      would thus appear that the attenuated LH seen with CRF(1) receptor antagonists
      depends on the hypothalamus-pituitary-adrenal (HPA) axis.

PMID- 11509204
TI  - The role of NMDA receptors in neonatal cocaine-induced neurotoxicity.
AB  - The present study assessed the ability of N-methyl-D-aspartate (NMDA) receptor
      antagonist, dizocilpine (MK-801), to modulate neonatal cocaine-induced
      neurobehavioral changes in the rat. Sprague-Dawley rats were randomly assigned on
      postnatal day 0 (PND 0) to one of four treatment groups. Treatments began on PND
      4 and continued until PND 10. Treatments consisted of an oral bolus of either
      cocaine HCl (40 mg/kg), (+)MK-801 (0.4 mg/kg), (+)MK-801 (0.4 mg/kg) followed 30
      min later with cocaine HCl (40 mg/kg) or 0.9% saline. On PND 21, 30, 40 and 60,
      males and females were examined for stress response using the cold-water swim
      test. Cocaine-treated male and female rats exhibited significantly diminished
      tolerance to cold-water stress compared to control and MK-801/cocaine-treated
      groups. In addition, neonatal exposure to cocaine was associated with increased
      severity of motor symptoms (tail twitches, wet dog shaking and convulsions)
      following the administration of NMDA (35 mg/kg). Treatment groups were also
      tested for pain sensitivity using the tail flick (TF) and hot plate (HP) methods.
      The results indicated that neonatal cocaine exposure altered pain sensitivity in
      both tests. NMDA receptor binding studies showed a significant increase in
      receptor densities in the hippocampus and hypothalamus of the cocaine-treated
      group compared to control. MK-801 administered to rat pups before cocaine
      treatment blocked the increase in receptor density. The results indicated that
      neonatal cocaine exposure was associated with altered responses to NMDA, stress
      tolerance and pain sensitivity. Moreover, the pretreatment with NMDA receptor
      antagonist, MK-801, abolished or attenuated these cocaine-induced neurobehavioral
      changes.

PMID- 11509205
TI  - Genetic-environment analysis of sensitivity and acute tolerance to ethanol in
      mice.
AB  - The purpose of this study was to characterize initial sensitivity (IS), acute
      functional tolerance (AFT), and rate of tolerance development to ethanol in lines
      of mice selected for aggression mice as well as to investigate the impact of
      isolate housing on these phenotypes. The results showed that for IS, there were
      no differences among treatment groups. For acute tolerance and rate of tolerance
      development, a Line x Sex x Housing interaction was present, with the response to
      housing being more pronounced in the low aggressive line than the high aggressive
      line, and the females being more affected than the males. Correlational analysis
      showed low to moderate associations between rate of tolerance development and IS,
      as well as between rate of tolerance and AFT. Housing condition significantly
      influenced female expression of ethanol phenotypes as compared to males. The line
      of the subject also influenced the magnitude of expression of these phenotypes.
      These findings suggest that environmental and genetic influences interact to
      influence acute tolerance and rate of tolerance development.

PMID- 11509206
TI  - Effect of nordihydroguaiaretic acid on behavioral impairment and neuronal cell
      death after forebrain ischemia.
AB  - The purpose of this study was to evaluate the neuroprotective effect of
      nordihydroguaiaretic acid (NDGA), an antioxidant and/or 5-lipoxygenase inhibitor,
      on ischemia-reperfusion injury behavioral pharmacologically and histologically in
      vivo. First, the antioxidant activity of NDGA was evaluated in vitro by measuring
      the production of thiobarbituric acid reactive substances (TBARS) in rat brain
      homogenate. Second, the effect of NDGA on learning and memory impairment induced
      by rat four-vessel occlusion transient ischemia was investigated with the Morris
      water-maze task. Third, the effect of NDGA on pyramidal cell loss in the
      hippocampus after transient ischemia was examined. NDGA inhibited the production
      of TBARS with an IC(50) of 0.1 microM, and significantly attenuated postischemic
      learning and memory impairment at 10 mg/kg. Furthermore, consecutive 4-day
      administration of NDGA at 10 mg/kg significantly reduced the postischemic
      neuronal death. NDGA was found to be potent and effective as an anti-ischemia
      reperfusion injury agent in terms of behavioral pharmacology and histology. The
      present results suggest that NDGA has beneficial effects on behavioral deficits
      and histological injury caused by ischemia-reperfusion.

PMID- 11509207
TI  - The effects of diazepam dependence and withdrawal on morphine-induced
      antinociception and changes in locomotion in male and female rats.
AB  - Male and female rats were exposed for 3 weeks to diazepam (DZ)-filled or empty
      capsules (CTR) prior to the daily administration of morphine (MOR, 5 mg/kg, IP)
      for 5 days. Thereafter, capsules were removed and 48 h later MOR was injected for
      the next 5 days. The tail-flick latency (TFL) was measured prior to and 15, 30,
      and 60 min after MOR assessed analgesia. Locomotion (LOC) was determined before
      and 15 min after injection. Prior to MOR injection (baseline), male rats were
      more sensitive to the thermal stimulus and were less active than female rats.
      Daily MOR injections neither affected the baseline TFL nor LOC. Regardless of
      gender, MOR produced greater analgesia in DZ-dependent and withdrawn rats than in
      CTR. MOR analgesia was greater in DZ-dependent male than in female rats. Gender
      differences in MOR analgesia were not of statistical significance in DZ-withdrawn
      rats. The first dose of MOR produced more depression of LOC in DZ-dependent
      female than in male rats. Across the time of MOR injections, female DZ-dependent
      and withdrawn rats were less active than CTR. LOC increased with repeated
      administration of MOR in all groups of rats. In summary, DZ dependence and
      withdrawal enhanced MOR analgesia in rats of both sexes. Regardless of chronic
      treatment, MOR produced more analgesia and less depression of LOC in male than in
      female rats. It is suggested that a decrease in the function of the GABAergic
      system plays a role in alteration of MOR analgesia.

PMID- 11509208
TI  - Iboga compounds reverse the behavioural disinhibiting and corticosterone effects
      of acute methamphetamine: Implications for their antiaddictive properties.
AB  - This study investigated the effects of pretreatment with the putative
      antiaddictive compound, ibogaine (IBO), and its synthetic derivative, 18
      methoxycoronaridine (18-MC), on the changes in behaviour in an elevated plus maze
      and the changes in corticosterone (CORT) produced by a low dose of
      methamphetamine (METH). In the elevated plus maze, the acute administration of
      METH (0.1 mg/kg ip, -20 min) produced an increase in both the number and the
      duration of open arm entries relative to saline (SAL)-treated controls. No effect
      of METH administration was observed on the total number of arm entries. These
      data indicated that METH alone produced either anxiolysis or behavioural
      disinhibition in this paradigm. More consistent with the latter possibility, the
      open arm behaviour of METH controls was associated with an increase in plasma
      levels of CORT, supporting a facilitatory role for CORT in this METH-induced
      effect. Pretreatment with both IBO and 18-MC (40 mg/kg ip, 19 h earlier)
      antagonized the behavioural disinhibiting effects of acute METH without altering
      locomotor activity. In addition, both iboga agents antagonized the increase in
      CORT produced by METH. These data provide insight into yet another potential
      mechanism through which iboga compounds may exert their antiaddictive effects, a
      reversal of the behavioural disinhibiting properties of stimulant drugs.
      Furthermore, these data indicate that this reversal is related to effects of
      iboga compounds on the stimulation of neuroendocrine systems by stimulant drugs.

PMID- 11509209
TI  - Competitive and noncompetitive NMDA antagonist effects in rats trained to
      discriminate lever-press counts.
AB  - The glutamate activated N-methyl-D-aspartate (NMDA) receptor may play a role in
      short-term memory processing. Among the evidence for this is that NMDA
      antagonists can impair accuracy in fixed consecutive number (FCN) tasks. This
      study was designed to further characterize this effect by examining NMDA
      antagonists differing in their cellular mechanisms of action. Rats were trained
      to respond under an FCN operant schedule, which required eight presses on one
      lever (counting lever) before one press at an alternate lever (reinforcement
      lever) would produce food reinforcement. The effects of three noncompetitive [MK
      801 (0.01-0.56 mg/kg); phencyclidine (0.3-3.0 mg/kg); memantine (1-10 mg/kg)] and
      two competitive [SDZ EAA 494 (0.3-3.0 mg/kg) and NPC 17742 (2.0-16 mg/kg)] NMDA
      antagonists were analyzed. MK-801 and phencyclidine decreased accuracy at doses
      not reducing response rates. Memantine, and both of the competitive antagonists,
      also reduced accuracy, but did so only at doses that markedly reduced response
      rates. These results suggest that both the affinity and the site bound on the
      NMDA glutamate receptor by antagonists can determine their effects on FCN
      performance. Subsequent studies investigated whether SCH 23390, a dopamine D1
      receptor antagonist, and NMDA could modulate the effects by phencyclidine and SDZ
      EAA 494, respectively, on FCN performance.

PMID- 11509210
TI  - Administration of minute quantities of 17beta-estradiol on the nasal area
      terminates early pregnancy in inseminated female mice.
AB  - It is well established that chemical emissions of novel males disrupt
      intrauterine implantation of fertilized ova in inseminated female mice, but the
      specific nature of these chemicals is not known. Given that novel males excrete
      androgens and estrogens in their urine and feces, the current experiments were
      designed to determine whether nasal application of these steroids could disrupt
      pregnancy. Nasal application of testosterone propionate to females during early
      pregnancy had no impact on gestation. However, nasal application of 17beta
      estradiol terminated all pregnancies in females at all doses greater than or
      equal to approximately 1 microg/day. Nasal application of 17beta-estradiol
      benzoate similarly terminated all pregnancies in females at very low doses. In
      subcutaneous administration, 17beta-estradiol is also the most potent steroid in
      disrupting pregnancy compared to other estrogens and androgens. These data
      suggest the possibility that males' emission of estrogens is among factors
      mediating the Bruce effect.

PMID- 11509211
TI  - The anxiolytic-like effect of nicotine undergoes rapid tolerance in a model of
      contextual fear conditioning in rats.
AB  - The effects of repeated administration of nicotine on contextual fear
      conditioning, locomotor activity, and pain threshold, were examined in rats. It
      was found that a single injection of nicotine prior to the training session
      (three 0.7-mA footshocks, each 0.5 s long), decreased the freezing reaction
      during the retest 24 h later. The locomotor activity was moderately enhanced, and
      the pain threshold remained unchanged. The baseline freezing measured immediately
      after administration of a single dose of nicotine was not significantly different
      from the saline-treated group. The anxiolytic-like effect of nicotine was as
      potent as that of midazolam, a benzodiazepine derivative. After five day-by-day
      injections, the anxiolytic-like effect of nicotine (0.6 mg/kg, sc) was no longer
      present, independently whether the last drug injection was given 24 h or 5 min
      (i.e., the sixth, additional, nicotine injection), prior to the training session.
      Thus, it appeared that the expression of tolerance to the nicotine-induced
      anxiolytic-like action did not require a direct stimulation of nicotinic
      receptors. Simultaneously, in this group of animals, nicotine caused a potent
      stimulation of locomotor activity in the open field test. The applied dosage and
      regimen of nicotine administration did not change rat pain threshold (flinch-jump
      test). Collectively, the present data showed for the first time, that short-term,
      intermittent, administration of nicotine was sufficient to induce tolerance to
      the anxiolytic-like effect of this drug, in the model of fear conditioning to
      context. Importantly, a clear dissociation between the locomotor and anxiolytic
      like effects of nicotine was present. This effect appeared independent also of
      changes in rat pain threshold. The possible mechanisms of this phenomenon are
      discussed.

PMID- 11509212
TI  - Locomotor-stimulating effects of indirect dopamine agonists are attenuated in
      Fawn hooded rats independent of postweaning social experience.
AB  - The effects of the indirect dopamine (DA) agonists cocaine and D-amphetamine on
      locomotor activity were examined in Fawn hooded (FH) rats and Wistar rats. The
      effect of isolation rearing was also examined to determine if it might have
      different effects in these two strains. Contrary to previous findings in other
      rat strains, only small increases in locomotor-stimulating responses to low doses
      of cocaine were observed in the present study as a result of isolation rearing.
      However, at higher cocaine doses, locomotor activity was substantially attenuated
      in FH rats relative to Wistar rats. A similar pattern of effects was observed for
      amphetamine in FH rats but only at the intermediate dose. The effects of strain
      and rearing were independent. There was no evidence for interactions between
      these factors.

PMID- 11509213
TI  - Effects of a novel potential antidepressant on the behavior and cortisol levels
      of isolated guinea pig pups.
AB  - A novel, potential antidepressant, E-6006 citrate (E-6039), dose-dependently
      reduced the vocalizations emitted by isolated guinea pig pups. The (+)-E-6006,
      but not the (-)-E-6006, enantiomer also reduced vocalizing. There were no
      reliable effects of E-6039 on locomotor activity, crouching, or other behavioral
      measures, but both E-6039 and the (+)-E-6006 enantiomer elevated plasma cortisol
      levels during isolation. The contrasting effects of E-6039 on vocalizations and
      plasma cortisol are discussed in terms of E-6039's putative ability to inhibit
      release of substance P. The reduction in the vocalizations of isolated guinea pig
      pups corroborates positive results with this drug in other antidepressant screens
      utilizing mice and rats, and provides further support for the potential of E-6039
      as an antidepressant compound.

PMID- 11509214
TI  - Blockade of drug-induced deficits in prepulse inhibition of acoustic startle by
      ziprasidone.
AB  - Ziprasidone, an antipsychotic with efficacy against core symptoms of
      schizophrenia and schizoaffective disorder, has a low incidence of extrapyramidal
      syndrome (EPS). Because of its high 5-HT(2A)/D(2) binding-affinity ratio and low
      EPS liability, ziprasidone is considered to belong to the newer class of "novel"
      antipsychotics typified by clozapine. Its unique pharmacological profile,
      however, distinguishes it from other novel agents. We evaluated ziprasidone in
      the prepulse inhibition (PPI) model, which is sensitive to clinically active
      antipsychotics. Male Wistar rats were tested in acoustic startle sessions in
      which some startle-eliciting stimuli were presented alone, and others were
      preceded by a weak prepulse. Administration of the dopamine agonist apomorphine
      (1 mg/kg) or the N-methyl-D-aspartate (NMDA) antagonist ketamine (10 mg/kg)
      significantly disrupted PPI. When coadministered with either of these compounds,
      clozapine (1-5.6 mg/kg sc) and ziprasidone (5.6-17.8 mg/kg po) significantly
      attenuated the declines in PPI. Haloperidol (0.03-0.56 mg/kg) also attenuated
      drug-induced deficits in PPI but to a lesser extent (and at higher doses) with
      ketamine than with apomorphine. Together, these data confirm that ziprasidone
      shares common effects in PPI models with other novel antipsychotics.
      Ziprasidone's affinity for non-D(2) receptors in the central nervous system may
      partly account for its attenuation of ketamine's effect.

PMID- 11509215
TI  - Long-term effects of alcohol drinking on cerebral glucose utilization in alcohol
      preferring rats.
AB  - The 2-[14C]deoxyglucose (2-DG) quantitative autoradiography technique was used to
      determine rates of local cerebral glucose utilization (LCGU) in discrete brain
      regions in alcohol-chronic (A-C), alcohol-deprived (A-D) and alcohol-naive (A-N)
      adult, male alcohol-preferring (P) rats. The hypothesis to be tested is that
      neuronal alterations occur as a result of chronic alcohol drinking and some of
      these alterations persist for long periods in the absence of alcohol. Following 6
      weeks of daily 4-h scheduled access sessions to 15% (v/v) ethanol and water,
      group A-D received only water during the sessions over the next 2 weeks, whereas
      groups A-C and A-N continued to receive ethanol-water and water-water,
      respectively. On the 14th day of the deprivation interval, LCGU rates were
      measured 1 h prior to the scheduled access period. Mean ethanol intake for the A
      D and A-C groups was 1.5+/-0.1 g ethanol/kg body weight per 4 h. LCGU rates were
      significantly decreased in 49 of 57 regions or subregions examined in the A-C
      group compared to the A-N group, including subregions of the cerebral cortex,
      hippocampus and structures in the mesocorticolimbic and nigrostriatal systems.
      Following alcohol deprivation, LCGU values in the A-D group were partially or
      completely returned to A-N levels in many, but not all, regions. In several
      limbic regions (e.g., ventral tegmental area, olfactory tubercle, medial
      prefrontal cortex, ventral pallidum and lateral septum), no recovery of LCGU
      rates was observed after 2 weeks of alcohol deprivation. This study demonstrates
      that chronic alcohol consumption produces significant reductions in functional
      neuronal activity in P rats, some of which persist in the absence of ethanol. The
      extent to which LCGU rates returned to normal levels following 2 weeks of alcohol
      deprivation varied among brain regions, suggesting that there are imbalanced
      interactions among and within several CNS sites, which do not reflect either the
      alcohol-naive or chronic alcohol-exposed state. Such neuronal imbalances may
      underlie relapse of alcohol drinking following prolonged abstinence.

PMID- 11509216
TI  - Passive exposure to a contextual discriminative stimulus reinstates cocaine
      seeking behavior in rats.
AB  - A significant problem in treating cocaine dependence is craving-induced relapse
      elicited by inadvertent (i.e., passive) exposure to cocaine-paired stimuli.
      Extinction/reinstatement of cocaine-seeking behavior in animals has been used to
      investigate this phenomenon. Most studies using this model have examined
      reinstatement by response-contingent exposure to discrete cocaine-paired stimuli.
      The present study expanded this research by examining passive (i.e., not
      contingent upon an operant response) exposure to a contextual cocaine-paired
      stimulus to better model craving elicited by inadvertent exposure to cocaine
      associated environmental stimuli. Rats underwent daily cocaine and saline self
      administration sessions that were identical to each other except for a
      discriminative stimulus (scented bedding) signaling cocaine availability (S+) or
      nonavailability (S-). Subsequently, they were placed into the self-administration
      chambers in the presence of neutral bedding. Reinforcement was not available and
      cocaine-seeking behavior (i.e., nonreinforced operant responses) was extinguished
      across days. Rats were then reintroduced to the S+ and S- stimuli. Presentation
      of the S+, but not the S-, elicited significant reinstatement of cocaine-seeking
      behavior. The results demonstrate that passive exposure to a contextual
      discriminative stimulus reinstates extinguished cocaine-seeking behavior.
      Furthermore, we suggest that reinstatement of cocaine-seeking behavior by passive
      exposure to cocaine-paired stimuli may provide a model of craving-induced relapse
      elicited by inadvertent exposure to a cocaine-associated environment.

PMID- 11509217
TI  - Acute exposure to a low or mild dose of soman: biochemical, behavioral and
      histopathological effects.
AB  - Effects of low to mild doses of soman on central and blood cholinesterase (ChE)
      activities and anxiety behavior were studied in mice 30 min, 24 h and 7 days
      after poisoning. At these two latter time points, histopathological consequences
      of soman intoxication were also studied. The 30-microg/kg dose of soman produced
      30 min after intoxication, about 35% of central ChE inhibition, and an anxiolytic
      effect without toxic signs or histopathological changes. The 50-microg/kg dose of
      soman produced at the same time, about 56% of central ChE inhibition, slight
      clinical signs of poisoning without convulsions, an anxiogenic effect with a
      slight hypolocomotion but no brain damage. A mild dose of soman (90 microg/kg)
      produced at this same time point about 80% of central ChE inhibition, and led to
      ataxia and tremors in every mouse and to convulsions in some of them. Thirty
      minutes and 24 h after poisoning, the behavioral tests revealed neither
      anxiolytic nor anxiogenic responses despite a clear hypolocomotion. Only mice
      that experienced long-lasting convulsions developed neuropathological changes.
      The functional implication of our results, as well as the biological relevance of
      blood vs. brain ChE levels, as an index of intoxication severity are discussed.

PMID- 11509218
TI  - Anxiolytic-like effects of DAIZAC, a selective high-affinity 5-HT(3) receptor
      antagonist, in the mouse elevated plus-maze.
AB  - Behavioral effects of desamino-3-iodozacopride (DAIZAC) [(S)-5-chloro-3-iodo-2
      methoxy-N-(1-azabicyclo[2.2.2]oct-3-yl)benzamide], a selective high-affinity 5
      HT(3) receptor antagonist (K(D) 0.14 nM), were evaluated in the mouse elevated
      plus-maze using the anxiolytic benzodiazepine, diazepam, as a positive control.
      DAIZAC treatment produced a significant dose-related increase in the time spent
      in the open arm. The increased total time in the open arm resulted from a
      significant dose-dependent increase in the number of entries into that arm. The
      minimum dose of DAIZAC associated with a statistically significant increase in
      entries and time spent in the open arm was 0.05 mg/kg ip, consistent with its
      high affinity for the 5-HT(3) receptor. DAIZAC did not affect the amount of time
      spent in the open arm after each entry. Thus, DAIZAC reduced apparent avoidance
      of the open arm when the animal was in the central compartment, without affecting
      active avoidance of that arm when the animal was in the exposed condition. The
      increase in the open-arm entries was accompanied by a corresponding reduction in
      the number of entries into the closed arm with a consequent reduction in the time
      spent in the closed arm. The time spent in the closed arm after each entry was
      not altered by DAIZAC administration. As such, the sole apparent effect of DAIZAC
      was to alter the choice of arm to enter when the animal was in the central
      compartment. Diazepam also significantly increased total time in the open arm;
      however, the increase was not attributable to a single behavioral factor. The
      anxiolytic-like effects of DAIZAC reached maximum by 20-30 min and returned to
      baseline levels by 90 min. Ex vivo binding studies found that levels of DAIZAC
      like activity assayed in brains of mice 25 min after DAIZAC injection were
      significantly correlated with the behavioral parameters associated with
      anxiolysis. These results indicate that DAIZAC produces dose-dependent anxiolytic
      like behavioral changes in the mouse elevated plus-maze that are correlated with
      brain DAIZAC-like activity.

PMID- 11509219
TI  - GABAergic and glutamatergic modulation of exploratory behavior in the dorsomedial
      hypothalamus.
AB  - Systemic injection of glutamate NMDA receptor antagonists or drugs that
      facilitate GABA(A)-mediated neurotransmission produces anxiolytic effects. The
      dorsomedial hypothalamic (DMH) region is proposed to be a possible site of action
      of these drugs. The objective of the present study was to investigate if
      facilitation of GABA(A)-mediated neurotransmission or blockade of NMDA receptors
      in the DMH would produce anxiolytic effects in the elevated plus-maze (EPM).
      Seven days after surgery, male Wistar rats with unilateral cannulas in the DMH
      were submitted to the behavioral studies. Results showed that midazolam, a
      benzodiazepine anxiolytic (30-60 nmol/0.3 microl), produced a dose-dependent
      increase in open arm exploration without changing the number of enclosed arm
      entries, indicating an anxiolytic effect. This effect was antagonized by previous
      treatment with flumazenil, a benzodiazepine receptor antagonist (60 nmol/0.3
      microl). Flumazenil alone had an anxiogenic effect, decreasing exploration of the
      open arms of the EPM. 2-Amino-7-phosphonoheptanoic acid (AP7), an NMDA receptor
      antagonist (0.2-2 nmol/0.3 microl), did not modify open arm exploration but
      decreased general exploratory activity. These results indicate that
      benzodiazepine receptors located in the DMH could modulate anxiety. Interference
      with NMDA receptor-mediated neurotransmission in this region, however, seems to
      change general exploratory activity rather than anxiety.

PMID- 11509221
TI  - Involvement of somatodendritic 5-HT(1A) receptors in Delta(9)
      tetrahydrocannabinol-induced hypothermia in the rat.
AB  - Previously, it has been reported that modulating serotonergic neurones by use of
      selective serotonin reuptake inhibitors (SSRI) can alter the hypothermic response
      produced by Delta(9)-tetrahydrocannabinol (Delta(9)-THC). The aim of the present
      study was to investigate the effect that activation or antagonism of 5
      hydroxytryptamine (5-HT(1A)) receptors has on Delta(9)-THC-induced hypothermia.
      Delta(9)-THC (0.5, 2 and 5 mg/kg iv) decreased body temperature in a dose-related
      manner. Whilst having no significant effect on body temperature when administered
      40 min prior to vehicle injection, the 5-HT(1A) receptor antagonist N-[2-[4-(2
      methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexanecarboxamide
      trihydrochloride (WAY 100635; 1 mg/kg sc) significantly potentiated the
      hypothermia produced by 2 and 5 mg/kg Delta(9)-THC. In order to investigate
      whether this effect was due to antagonism at somatodendritic autoreceptors in
      midbrain raphe nuclei, WAY 100635 or the 5-HT(1A) agonist 8-hydroxy-(di-n
      propylamino) tetralin (8-OH-DPAT) was microinjected into either the median raphe
      nuclei (MRN) or dorsal raphe nuclei (DRN) 40 min prior to Delta(9)-THC injection.
      Following microinjection into the DRN, neither WAY 100635 (0.5 nmol/0.5 microl/10
      s) nor 8-OH-DPAT (15.2 nmol/0.5 microl/10 s) had any significant effect on
      Delta(9)-THC-induced hypothermia. However, WAY 100635 when microinjected into the
      MRN significantly potentiated Delta(9)-THC-induced hypothermia, and 8-OH-DPAT
      microinjected into the MRN significantly inhibited Delta(9)-THC-induced
      hypothermia. It is suggested from these studies that the potentiation of Delta(9)
      THC-induced hypothermia by WAY 100635 when administered peripherally is mainly
      due to antagonism at somatodendritic 5-HT(1A) autoreceptors in the MRN.

PMID- 11509220
TI  - MK-801 induced retrieval, but not acquisition, deficits for passive avoidance
      conditioning.
AB  - Two experiments using a state-dependent retention (SDR) design determined whether
      MK-801 blocked the acquisition and retention of an avoidance response. In
      Experiments 1 and 2, rats were trained and tested 30 min after injections of
      either saline or MK-801 (0.05 and 0.10 mg/kg, respectively). Two minutes after
      training, subjects were immediately tested, and in both experiments, the
      avoidance response was acquired. The 24-h retention tests for Experiment 1
      revealed that the data marginally supported a SDR interpretation. In Experiment
      2, the dose of MK-801 was increased to 0.10 mg/kg, and the results showed that MK
      801 rendered passive avoidance (PA) state-dependent. These experiments indicate
      that neither the 0.05 nor 0.10 mg/kg doses of MK-801 prevented acquisition of the
      avoidance response and that the latter dose rendered memory for PA training state
      dependent. It is suggested that doses of MK-801 that did not impair PA learning
      can function as a cue state and influence expression of memory for PA.

PMID- 11509222
TI  - The role of the hypothalamic melanocortin system in behavioral appetitive
      processes.
AB  - Much evidence suggests that the hypothalamic melanocortin (MC) system plays an
      important role in the control of food intake. However, investigations of the
      potential behavioral mechanisms have been limited to measures of aversion. The
      purpose of the present experiment was to assess whether other behavioral
      consequences of administration of MC peptides were similar to those produced by 0
      or 24-h food deprivation, respectively. Rats were first trained while food
      deprived that a tone predicted the delivery of peanut oil. They then received
      exposure to oil under food deprivation, satiation, intra-third-cerebroventricular
      (i3vt) infusion of MTII (a potent MC agonist) or SHU-9119 (a potent MC
      antagonist). All rats were then tested during extinction for levels of responding
      to the tone under food satiation. Previous results demonstrated that sated
      exposure reduces subsequent test responding to the tone. During the present
      extinction test, rats that received sated exposure exhibited reduced responding
      to the tone, relative to rats that received deprived exposure. Unlike satiation,
      rats that received exposure after MTII exhibited continued high levels of
      responding to the tone. Further, rats that received SHU-9119 exhibited a small
      reduction in responding. These data suggest that MTII and SHU-9119 do not
      influence intake via the same mechanisms as hunger and food satiation,
      respectively.

PMID- 11509223
TI  - Nefiracetam improves Morris water maze performance following traumatic brain
      injury in rats.
AB  - Nefiracetam, a pyrrolidone derivative, is a nootropic agent that has facilitated
      cognitive function in a wide variety of animal models of cognitive dysfunction.
      The purpose of this study was to investigate the efficacy of the chronic
      postinjury administration of nefiracetam (DM-9384) in improving cognitive
      performance following central fluid percussion brain injury in rats. Twenty-four
      hours following surgical preparation, a sham injury or a moderate fluid
      percussive injury (2.1 atm) was delivered. Nefiracetam was administered
      chronically (0 or 9 mg/kg, po, for sham animals and 0, 3, or 9 mg/kg for injured
      animals) on postinjury days 1-15. Cognitive performance was assessed using the
      Morris water maze (MWM) on postinjury days 11-15. Chronic administration of 3 and
      9 mg/kg nefiracetam attenuated MWM deficits produced by central fluid percussive
      brain injury. Importantly, the MWM performance of the injured animals treated
      with 9 mg/kg did not significantly differ from uninjured, sham animals. The 9
      mg/kg dose of nefiracetam did not have a positive or negative effect on MWM
      performance of uninjured animals. The results of the present experiment suggest
      that a nootropic such as nefiracetam may be an appropriate treatment for trauma
      induced cognitive dysfunction.

PMID- 11509224
TI  - The role of dopamine in the timing of Pavlovian conditioned keypecking in ring
      doves.
AB  - The effect of dopaminergic drugs on the timing of conditioned keypecking in ring
      doves was studied in two experiments. Subjects were given pairings of a keylight
      with food and the temporal distribution of keypecks was obtained during
      unreinforced probe trials. Experiment 1 demonstrated that injections of pimozide
      before each session immediately decreased response rates but shifted timing
      distributions gradually to the right over several days of treatment. Experiment 2
      showed similar results using a longer interstimulus interval (ISI). No shifts
      were observed when the drug was injected after training sessions, or when a
      delay, identical to each subject's average latency to eat during the drug
      condition, was inserted between keylight offset and food presentation.
      Consequently, the shifts in timing were mediated neither by mere accumulation of
      the drug nor a delay from keylight offset to food presentation resulting from the
      drug's ability to slow motor processes. The results suggest that pimozide
      modulates response rate through its effect on motor processes or incentive value,
      and response timing through a conditioned response (CR) to injection-related cues
      established via their repeated pairings with the drug.

PMID- 11509225
TI  - Enhanced corticosterone release after a modified forced swim test in Fawn hooded
      rats is independent of rearing experience.
AB  - Recent findings have demonstrated that Fawn hooded (FH/Har) rats exhibit enhanced
      plasma corticosterone (CORT) responses compared to Wistar rats after exposure to
      an open field, whereas this effect was not influenced by early social experience.
      In contrast, it was found that behavior in a modified version of the Porsolt
      Forced Swim Test (Porsolt FST) was affected by both strain and social experience.
      An important part of this study included modifications of the Porsolt FST that
      allowed separation of multiple behavioral endpoints. The present experiment was
      conducted to determine if FH/Har rats also exhibit enhanced CORT responses after
      exposure to the modified forced swim test, and whether CORT levels might predict
      the behavioral response in this context. After the initial exposure in the
      modified forced swim test FH/Har rats had higher CORT levels than Wistar rats,
      but this difference was not affected by isolation rearing. However, CORT levels
      were not correlated with the main behavioral measures assayed in this test.
      Nonetheless, the data confirm that FH/Har rats have altered HPA axis responses to
      stressors.

PMID- 11509226
TI  - Ethanol, errors, and the speed-accuracy trade-off.
AB  - Ethanol has been shown to have a relatively greater effect on error rates in
      speeded tasks than temazepam, and this may be due to a differential effect on the
      speed-accuracy trade-off (SATO). This study used different instruction sets to
      influence the SATO. Forty-nine healthy volunteers (24 males, aged 18-41 years)
      were allocated at random to one of three instruction conditions--emphasising
      accuracy, neutral, and emphasising speed. After familiarisation, they took part
      in two sessions spaced at least 4 days apart in which they received either
      ethanol (0.8 g/kg, max 60 g males, 50 g females) or placebo in randomised order.
      Tests were administered starting at 30 and 75 min postdrug. Instructions
      significantly affected performance. In two maze tasks, one on paper, the other on
      a pen computer, the pattern of instruction effects was as expected. A significant
      increase in errors with ethanol was seen for both maze tasks, and there was a
      tendency to speed up with ethanol (significant only for the pen computer task).
      Responses to fixed stimulus sequences on the Four-Choice Reaction Test also
      showed a tendency to speed up and an increase in errors with ethanol, while all
      other tests showed both slowing and increases in errors with ethanol compared to
      placebo. Error scores are consistently increased by ethanol in all test
      situations, while the effects of ethanol on speed are variable across tests.

PMID- 11509227
TI  - Modulation of 5-HT(2A) receptor-mediated head-twitch behaviour in the rat by 5
      HT(2C) receptor agonists.
AB  - The pharmacology of several commonly described 5-hydroxytryptamine (5-HT)(2C)
      receptor agonists was investigated in vivo and in vitro at rat 5-HT(2A), 5
      HT(2B), and 5-HT(2C) receptors. The 5-HT(2C) receptor agonist, (S)-2-(6-chloro-5
      fluoroindol-1-yl)-1-methylethylamine fumarate (Ro 60-0175), did not induce a
      significant head-twitch response when given alone, yet when administered to rats
      subsequent to an acute challenge with the selective 5-HT(2C) receptor antagonist,
      6-chloro-5-methyl-1-[6-(2-methylpyridin-3-yloxy) pyridin-3-yl carbomyl] indoline
      (SB-242084), a robust head-twitch response was observed which was blocked by the
      selective 5-HT(2A) receptor antagonists R(+)-alpha-(2,3-dimethoxyphenyl)-1-[2-(4
      fluorophenyl-ethyl)]-4-piperidine-methanol (MDL 100907) or ketanserin. The
      preferential 5-HT(2C) receptor agonists Ro 60-0175, 6-chloro-2-[1-piperazinyl]
      pyrazine HCl (MK-212), 1-(3-chlorophenyl)piperazine hydrochloride (mCPP), 1-(3
      trifluoromethylphenyl)piperazine hydrochloride (TFMPP), and (S)-3-[(2,3-dihydro-5
      methoxy-1H-inden-4-yl)oxy]-pyrollidine HCl (ORG-37684), the 5-HT(2A/2C) receptor
      agonist 2,5-dimethoxy-4-iodoamphetamine (DOI), the 5-HT(2B) receptor agonist 1-[5
      thienylmethoxy-1-1H-3-indoyl] propan-2-amine hydrochloride (BW-723C86), and nor-D
      fenfluramine were administered to rats subsequent to an acute challenge of SB
      242084. Under such conditions, each agonist, with the exception of BW-723C86,
      induced a dose-dependent increase in the incidence of head twitches. The
      pharmacology of the same agonists was determined at cloned rat 5-HT(2) receptors
      using a fluorometric imaging plate reader (FLIPR). Both the in vivo and in vitro
      data suggest that for some ligands, previous reports have overestimated their in
      vivo selectivity for the 5-HT(2C) receptor.

PMID- 11509228
TI  - Effects of amphetamine and sydnocarb on dopamine release and free radical
      generation in rat striatum.
AB  - Microdialysis technique was used to compare the effects of four repeated
      intraperitoneal administrations of two psychostimulant drugs, D-amphetamine and
      sydnocarb, at the equimolar doses 5 and 23.8 mg/kg, respectively, on the
      extracellular level of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and
      hydroxyl radicals (.OH) in the dorsal striatum of freely moving 3-month-old male
      Wistar rats 250-300 g in weight. D-amphetamine caused immediate increase of DA
      concentration up to 950% with quick decline towards baseline values thereafter,
      followed by much less increase after further injections. Sydnocarb elicited
      moderate elevation in DA level achieving 400% after the fourth injection. D
      amphetamine induced deep decrease in DOPAC concentration, while sydnocarb caused
      its increase after the first and second dosing. Both drugs enhanced generation of
      .OH, the effect of D-amphetamine was more pronounced. D-Amphetamine induced more
      intensive stereotyped behavior in rats compare to sydnocarb. It is concluded that
      the psychostimulant action of sydnocarb is accompanied by facilitation of the
      central dopaminergic transmission in rat neostriatum and followed by less
      pronounced neurotoxic effect than that of D-amphetamine.

PMID- 11509229
TI  - Cyclooxygenase 1 is not essential for hypophagic responses to interleukin-1 and
      endotoxin in mice.
AB  - Numerous studies have shown that the effects of interleukin-1 (IL-1) and
      endotoxin (LPS) on behavior are sensitive to cyclooxygenase (COX) inhibitors.
      However, neither the location of the COX involved nor the specific isoform, COX1
      or COX2, is known. A previous study using selective COX1 and COX2 inhibitors did
      not provide an unequivocal answer. Therefore, we tested the response of sweetened
      milk ingestion to IL-1 and LPS in mice in which the COX1 or the COX2 gene was
      deleted (COX1ko and COX2ko). When IL-1beta was administered 90 min before the
      milk, COX1ko mice showed responses similar to those of normal mice. In contrast,
      COX2ko mice exhibited responses considerably less than normal, with some mice
      showing no response. Indomethacin pretreatment almost prevented the feeding
      responses to IL-1 in normal and COX1ko mice. The milk intake response to LPS in
      COX1ko mice was like that of normal mice. The results from COX1ko mice suggest
      that COX1 is not necessary for the decreased milk intake following IL-1 and LPS.
      The results from COX2ko mice are consistent with the involvement of COX2 in the
      IL-1-induced depression of milk intake, but other mechanisms may effect decreases
      in sweetened milk intake.

PMID- 11509230
TI  - The survival of motor neurons (SMN) protein interacts with the snoRNP proteins
      fibrillarin and GAR1.
AB  - BACKGROUND: The survival of motor neurons (SMN) protein is the protein product of
      the spinal muscular atrophy (SMA) disease gene. SMN and its associated proteins
      Gemin2, Gemin3, and Gemin4 form a large complex that plays a role in snRNP
      assembly, pre-mRNA splicing, and transcription. The functions of SMN in these
      processes are mediated by a direct interaction of SMN with components of these
      machineries, such as Sm proteins and RNA helicase A. RESULTS: We show that SMN
      binds directly to fibrillarin and GAR1. Fibrillarin and GAR1 are specific markers
      of the two classes of small nucleolar ribonucleoprotein particles (snoRNPs) that
      are involved in posttranscriptional processing and modification of ribosomal RNA.
      SMN interaction requires the arginine- and glycine-rich domains of both
      fibrillarin and GAR1 and is defective in SMN mutants found in some SMA patients.
      Coimmunoprecipitations demonstrate that the SMN complex associates with
      fibrillarin and with GAR1 in vivo. The inhibition of RNA polymerase I
      transcription causes a transient redistribution of SMN to the nucleolar periphery
      and loss of fibrillarin and GAR1 colocalization with SMN in gems. Furthermore,
      the expression of a dominant-negative mutant of SMN (SMNDeltaN27) causes snoRNPs
      to accumulate outside of the nucleolus in structures that also contain components
      of gems and coiled (Cajal) bodies. CONCLUSIONS: These findings identify
      fibrillarin and GAR1 as novel interactors of SMN and suggest a function for the
      SMN complex in the assembly and metabolism of snoRNPs. We propose that the SMN
      complex performs functions necessary for the biogenesis and function of diverse
      ribonucleoprotein complexes.

PMID- 11509231
TI  - Control of astrocyte Ca(2+) oscillations and waves by oscillating translocation
      and activation of protein kinase C.
AB  - BACKGROUND: Glutamate-induced Ca2+ oscillations and waves coordinate astrocyte
      signaling responses, which in turn regulate neuronal excitability. Recent studies
      have suggested that the generation of these Ca2+ oscillations requires a negative
      feedback that involves the activation of conventional protein kinase C (cPKC).
      Here, we use total internal reflection fluorescence (TIRF) microscopy to
      investigate if and how periodic plasma membrane translocation of cPKC is used to
      generate Ca2+ oscillations and waves. RESULTS: Glutamate stimulation of
      astrocytes triggered highly localized GFP-PKCgamma plasma membrane translocation
      events, induced rapid oscillations in GFP-PKCgamma translocation, and generated
      GFP-PKCgamma translocation waves that propagated across and between cells. These
      translocation responses were primarily mediated by the Ca2+-sensitive C2 domains
      of PKCgamma and were driven by localized Ca2+ spikes, by oscillations in Ca2+
      concentration, and by propagating Ca(2+) waves, respectively. Interestingly, GFP
      conjugated C1 domains from PKCgamma or PKCdelta that have been shown to bind
      diacylglycerol (DAG) also oscillated between the cytosol and the plasma membrane
      after glutamate stimulation, suggesting that PKC is repetitively activated by
      combined oscillating increases in Ca(2+) and DAG concentrations. The expression
      of C1 domains, which increases the DAG buffering capacity and thereby delays
      changes in DAG concentrations, led to a marked prolongation of Ca(2+) spikes,
      suggesting that PKC activation is involved in terminating individual Ca(2+)
      spikes and waves and in defining the time period between Ca(2+) spikes.
      CONCLUSIONS: Our study suggests that cPKCs have a negative feedback role on
      Ca(2+) oscillations and waves that is mediated by their repetitive activation by
      oscillating DAG and Ca(2+) concentrations. Periodic translocation and activation
      of cPKC can be a rapid and markedly localized signaling event that can limit the
      duration of individual Ca(2+) spikes and waves and can define the Ca(2+) spike
      and wave frequencies.

PMID- 11509232
TI  - Downregulation of Jun kinase signaling in the amnioserosa is essential for dorsal
      closure of the Drosophila embryo.
AB  - BACKGROUND: During Drosophila embryogenesis, Jun kinase (JNK) signaling has been
      shown to play a key role in regulating the morphogenetic process of dorsal
      closure, which also serves as a model for epithelial sheet fusion during wound
      repair. During dorsal closure the JNK signaling cascade in the dorsal-most
      (leading edge) cells of the epidermis activates the AP-1 transcription factor
      comprised of DJUN and DFOS that, in turn, upregulates the expression of the dpp
      gene. DPP is a secreted morphogen that signals lateral epidermal cells to
      elongate along the dorsoventral axis. The leading edge cells contact the
      peripheral cells of a monolayer extraembryonic epithelium, the amnioserosa, which
      lies on the dorsal side of the embryo. Focal complexes are present at the dorsal
      most membrane of the leading edge cells, where they contact the amnioserosa.
      RESULTS: We show that the JNK signaling cascade is initially active in both the
      amnioserosa and the leading edge of the epidermis. JNK signaling is downregulated
      in the amnioserosa, but not in the leading edge, prior to dorsal closure. The
      subcellular localization of DFOS and DJUN is responsive to JNK signaling in the
      amnioserosa: JNK activation results in nuclear localization of DFOS and DJUN; the
      downregulation of JNK signaling results in the relocalization of DFOS and DJUN to
      the cytoplasm. The HINDSIGHT (HNT) Zn-finger protein and the PUCKERED (PUC) JNK
      phosphatase are essential for downregulation of the JNK cascade in the
      amnioserosa. Persistent JNK activity in the amnioserosa leads to defective focal
      complexes in the adjacent leading edge cells and to the failure of dorsal
      closure. CONCLUSIONS: Focal complexes are assembled at the boundary between high
      and low JNK activity. In the absence of focal complexes, miscommunication between
      the amnioserosa and the leading edge may lead to a premature "stop" signal that
      halts dorsalward migration of the leading edge. Spatial and temporal regulation
      of the JNK signaling cascade may be a general mechanism that controls tissue
      remodeling during morphogenesis and wound healing.

PMID- 11509233
TI  - Xenoinfection of nonhuman primates by feline immunodeficiency virus.
AB  - New viral infections in humans usually result from viruses that have been
      transmitted from other species as zoonoses. For example, it is accepted widely
      that human immunodeficiency virus (HIV) is the result of the propagation and
      adaptation of a simian immunodeficiency virus (SIV) from nonhuman primates to man
      [1]. Previously, we reported productive infection of primary human cells in vitro
      by feline immunodeficiency virus (FIV) [2], a lentivirus that causes an
      immunodeficiency syndrome in cats similar to HIV in humans [3]. The present study
      extends these findings by demonstrating that cynomolgus macaques (Macaca
      fasicularis) infected with FIV exhibited clinical signs, including depletion of
      CD4+ cells and weight loss, that are consistent with FIV infection. The
      development of an antibody response to FIV gag-encoded proteins and detection of
      virus-specific sequences in sera, blood-derived cells, and necropsied tissue
      accompanied these changes. Moreover, the reactivation of FIV replication from
      latently infected cells was observed after stimulation in vitro with phorbol
      esters and in vivo with tetanus toxoid. The proposed use of lentiviruses in human
      gene therapy [4, 5] and of nonhuman cells and organs in xenotransplantation [6]
      has raised concerns about zoonoses as potential sources of new human pathogens.
      Therefore, the study of FIV infection of primate cells may provide insight into
      the principles underlying retroviral xenoinfections.

PMID- 11509234
TI  - Quality control in the endoplasmic reticulum: PDI mediates the ER retention of
      unassembled procollagen C-propeptides.
AB  - Quality control within the endoplasmic reticulum (ER) is thought to be mediated
      by the interaction of a folding protein with one or several resident ER proteins
      [1]. Protein disulphide isomerase (PDI) is one such ER resident protein that has
      been previously shown to interact with proteins during their folding and assembly
      pathways [2, 3]. It has been assumed that, as a consequence of this interaction,
      unassembled proteins are retained within the ER. Here, we experimentally show
      that this is indeed the case. We have taken advantage of our previous finding
      that PDI interacts with procollagen chains early on in their assembly pathway [2]
      to address the role of this protein in directly retaining unassembled chains
      within the ER. Our experimental approach involved expressing individual C
      propeptide domains from different procollagen chains in mammalian cells and
      determining the ability of these domains to interact with PDI and to be secreted.
      The C-propeptide from the proalpha2(I) chain was retained within the cell, where
      it formed a complex with PDI. Conversely, the C-propeptide from the
      proalpha1(III) chain did not form a complex with PDI and was secreted. Both
      domains were secreted, however, from a stable cell line expressing a secreted
      form of PDI lacking its ER retrieval signal. Hence, we have demonstrated directly
      that the intracellular retention of one substrate for ER quality control is due
      to an interaction with PDI.

PMID- 11509235
TI  - Resistance of RNA-mediated TGS to HC-Pro, a viral suppressor of PTGS, suggests
      alternative pathways for dsRNA processing.
AB  - In plants, double-stranded (ds) RNA that is degraded to small (sm) RNAs that are
      approximately 23 nucleotides in length can trigger the degradation of homologous
      RNAs in the cytoplasm (posttranscriptional gene silencing or PTGS) and de novo
      methylation of homologous DNA in the nucleus [1]. PTGS is similar to quelling in
      fungi [2] and RNAi in animals [3]. RNA-directed DNA methylation (RdDM) can lead
      to transcriptional gene silencing (TGS) and the methylation of homologous target
      promoters if dsRNAs containing promoter sequences are involved [4]. HC-Pro is a
      plant viral suppressor of PTGS that acts by preventing the accumulation of smRNAs
      [5, 6] that provide the specificity determinant for homologous RNA degradation [7
      10]. Here, we show that HC-Pro does not suppress TGS induced by promoter dsRNA.
      Moreover, the amount of promoter smRNAs is elevated 5-fold in the presence of HC
      Pro, and target promoter methylation is slightly increased without a concomitant
      rise in the level of promoter dsRNA. The promoter dsRNA, which is not
      polyadenylated, failed to trigger substantial degradation of polyadenylated,
      single-stranded promoter RNA. The differential effects of HC-Pro on smRNA
      accumulation associated with dsRNA-mediated TGS and at least some cases of PTGS
      suggest that dsRNA processing can occur by alternative pathways, and they support
      the idea that RdDM is triggered by smRNAs.

PMID- 11509236
TI  - Myosin V-mediated vacuole distribution and fusion in fission yeast.
AB  - The class V myosins are actin-based motors that move a variety of cellular
      cargoes [1]. In budding yeast, their activity includes the relocation of a
      portion of the vacuole from the mother cell to the bud [2, 3]. Fission yeast
      cells contain numerous (approximately 80) small vacuoles. When S. pombe cells are
      placed in water, vacuoles fuse in response to osmotic stress [4]. Fission yeast
      possess two type V myosin genes, myo51(+) and myo52(+) [5]. In a myo51Delta
      strain, vacuoles were distributed throughout the cell, and mean vacuole diameter
      was identical to that seen in wild-type cells. When myo51Delta and wild-type
      cells were placed in water, vacuoles enlarged by fusion. In myo52Delta cells, by
      contrast, vacuoles were smaller and mostly clustered around the nucleus, and
      fusion in water was largely inhibited. When cells containing GFP-Myo52 were
      placed in water, Myo52 was seen to redistribute from the cell poles to the
      surface of the fusing vacuoles. Vacuole fusion in fission yeast was inhibited by
      the microtubule drug thiabendazole (TBZ) but not by the actin inhibitor
      latrunculin B. This is the first demonstration of the involvement of a type V
      myosin, possibly via an interaction with microtubules, in homotypic membrane
      fusion.

PMID- 11509237
TI  - CpG methylation regulates the Igf2/H19 insulator.
AB  - The differentially methylated 5'-flank of the mouse H19 gene unidirectionally
      regulates the communication between enhancer elements and gene promoters and
      presumably represses maternal Igf2 expression in vivo [1-6]. The specific
      activation of the paternally inherited Igf2 allele has been proposed to involve
      methylation-mediated inactivation of the H19 insulator function during male
      germline development [1-4, 6]. Here, we addressed the role of methylation by
      inserting a methylated fragment of the H19-imprinting control region (ICR) into a
      nonmethylated episomal H19 minigene construct, followed by the transfection of
      ligation mixture into Hep3B cells. Individual clones were expanded and analyzed
      for genotype, methylation status, chromatin conformation, and insulator function.
      The results show that the methylated status of the H19 ICR could be propagated
      for several passages without spreading into the episomal vector. Moreover, the
      nuclease hypersensitive sites, which are typical for the maternally inherited H19
      ICR allele [1], were absent on the methylated ICR, underscoring the suggestion
      that the methylation mark dictates parent of origin-specific chromatin
      conformations [1] that involve CTCF [2]. Finally, the insulator function was
      strongly attenuated in stably maintained episomes. Collectively, these results
      provide the first experimental support that the H19 insulator function is
      regulated by CpG methylation.

PMID- 11509238
TI  - Motor domain-dependent localization of myo1b (myr-1).
AB  - Myosin-I is the single-headed, membrane binding member of the myosin superfamily
      that plays a role in membrane dynamics and transport [1-6]. Its molecular
      functions and its mechanism of regulation are not known. In mammalian cells,
      myosin-I is excluded from specific microfilament populations, indicating that its
      localization is tightly regulated. Identifying the mechanism of this
      localization, and the specific actin populations with which myosin-I interacts,
      is crucial to understanding the molecular functions of this motor. eGFP chimeras
      of myo1b [7] were imaged in live and fixed NRK cells. Ratio-imaging microscopy
      shows that myo1b-eGFP concentrates within dynamic areas of the actin
      cytoskeleton, most notably in membrane ruffles. Myo1b-eGFP does not associate
      with stable actin bundles or stress fibers. Truncation mutants consisting of the
      motor or tail domains show a partially overlapping cytoplasmic localization with
      full-length myo1b, but do not concentrate in membrane ruffles. A chimera
      consisting of the light chain and tail domains of myo1b and the motor domain from
      nonmuscle myosin-IIb (nmMIIb) concentrates on actin filaments in ruffles as well
      as to stress fibers. In vitro motility assays show that the exclusion of myo1b
      from certain actin filament populations is due to the regulation of the
      actomyosin interaction by tropomyosin. Therefore, we conclude that tropomyosin
      and spatially regulated actin polymerization play important roles in regulating
      the function and localization of myo1b.

PMID- 11509239
TI  - Annexin 2 has an essential role in actin-based macropinocytic rocketing.
AB  - Annexin 2 is a Ca(2+) binding protein that binds to and aggregates secretory
      vesicles at physiological Ca(2+) levels [1] and that also associates Ca(2+)
      independently with early endosomes [2, 3]. These properties suggest roles in both
      exocytosis and endocytosis, but little is known of the dynamics of Annexin 2
      distribution in live cells during these processes. We have used evanescent field
      microscopy to image Annexin 2-GFP in live, secreting rat basophilic leukemia
      cells and in cells performing pinocytosis. Although we found no evidence of
      Annexin 2 involvement in exocytosis, we observed an enrichment of Annexin 2-GFP
      in actin tails propeling macropinosomes. The association of Annexin 2-GFP with
      rocketing macropinosomes was specific because Annexin 2-GFP was absent from the
      actin tails of rocketing Listeria. This finding suggests that the association of
      Annexin 2 with macropinocytic rockets requires native pinosomal membrane. Annexin
      2 is necessary for the formation of macropinocytic rockets since overexpression
      of a dominant-negative Annexin 2 construct abolished the formation of these
      structures. The same construct did not prevent the movement of Listeria in
      infected cells. These results show that recruitment of Annexin 2 to nascent
      macropinosome membranes 16656is an essential prerequisite for actin
      polymerization-dependent vesicle locomotion.

PMID- 11509240
TI  - Photoactivation of DNA thiobases as a potential novel therapeutic option.
AB  - The thiopurines, 6-thioguanine and 6-mercaptopurine, are antileukemic agents that
      are incorporated into DNA following retrieval by the purine salvage pathway (see
      [1] for a review). Their toxicity requires active DNA mismatch repair (MMR), and
      thiopurine resistance is an acknowledged phenotype of MMR-defective cells [2, 3].
      In addition to these direct cytotoxic effects, DNA thiobases have distinctive
      photochemical properties [4], the therapeutic potential of which has not been
      extensively evaluated. We report here that the thiopyrimidine nucleoside 4
      thiothymidine is incorporated into DNA. It does not induce MMR-related toxicity,
      but it interacts synergistically with UVA light and dramatically sensitizes
      cultured human cells to very low, nonlethal UVA doses. 4-thiothymidine induced
      UVA dose enhancements of around 100-fold in DNA repair-proficient cells.
      Nucleotide excision repair-defective xeroderma pigmentosum cells were sensitized
      up to 1000-fold, implicating bulky DNA photoproducts in the lethal effect. The
      synergistic action of thiothymidine plus UVA required thymidine kinase,
      indicating a selective toxicity toward rapidly proliferating cells. Cooperative
      UVA cytotoxicity is a general property of DNA thiobases, and 6-thioguanine and 4
      thiodeoxyuridine were also UVA sensitizers. Thiobase/UVA treatment may offer a
      novel therapeutic approach for the clinical management of nonmalignant conditions
      like psoriasis or for superficial tumors that are accessible to phototherapy.

PMID- 11509241
TI  - Sightless has homology to transmembrane acyltransferases and is required to
      generate active Hedgehog protein.
AB  - Proteins of the Hedgehog (Hh) family act as important developmental signals in a
      variety of species [1]. Hh proteins are synthesized as full-length precursors
      that are autocatalytically cleaved by their C-terminal domains to release the
      signaling N-terminal domains [2]. The addition of a cholesterol molecule to the C
      terminus of the signaling domain is concomitant with cleavage [3]. Vertebrate
      Sonic hedgehog (Shh) proteins have also been shown to acquire a fatty acid chain
      on the N-terminal cysteine of this domain [4], which is required for a subset of
      their in vivo functions [5, 6]. A mutation of the corresponding cysteine in
      Drosophila Hh transforms it into a dominant-negative protein [6]. We have
      identified a novel gene, sightless (sit), which is required for the activity of
      Drosophila Hh in the eye and wing imaginal discs and in embryonic segmentation.
      sit acts in the cells that produce Hh, but does not affect hh transcription, Hh
      cleavage, or the accumulation of Hh protein. sit encodes a conserved
      transmembrane protein with homology to a family of membrane-bound
      acyltransferases. The Sit protein could act by acylating Hh or by promoting other
      modifications or trafficking events necessary for its function.

PMID- 11509243
TI  - Human babies in germ-line juggernaut.
AB  - Mediawatch: A report on infertility treatment that mixed mitochondria from a
      third party to the union of egg and sperm caused little stir initially in the US
      but ignited the British press, writes Richard Harris.

PMID- 11509244
TI  - Drawing new GM battle lines.
AB  - The legal battles over GM crop trials in Europe are hotting up, reports Nigel
      Williams.

PMID- 11509245
TI  - New efforts develop therapeutic antibodies.
AB  - Since the development of monoclonal antibodies twenty-five years ago, researchers
      and biotech companies have been looking to develop therapeutic uses for them.
      Michael Gross looks at some of the latest efforts.

PMID- 11509246
TI  - Apple Eden looks east.

PMID- 11509247
TI  - Presenilins.

PMID- 11509248
TI  - Green fluorescent tortoiseshell mice.

PMID- 11509249
TI  - Mismatch repair: praying for genome stability.

PMID- 11509250
TI  - Trains with a view to sickness.

PMID- 11509251
TI  - Nucleocytoplasmic transport: diffusion channel or phase transition?
AB  - How exactly large molecules translocate through nuclear pores has been mysterious
      for a long time. Recent kinetic measurements of transport rates through the pore
      have led to a novel translocation model that elegantly combines selectivity with
      very high transport rates.

PMID- 11509252
TI  - Axoglial junctions: separate the channels or scramble the message.
AB  - Axoglial junctions flank the nodes of Ranvier in myelinated nerves. These large
      cell adhesion complexes have an essential role in sequestering potassium channels
      located under the myelin sheath from nodal sodium channels. Recent studies have
      shed new light on the composition and function of axoglial junctions.

PMID- 11509253
TI  - Plant cell walls: wall-associated kinases and cell expansion.
AB  - Arabidopsis has a family of five cell wall-associated protein kinases (WAKs) with
      properties suggestive of transmembrane sensors between the cell wall and the
      cytoplasm. Recent results show that WAKs are bound to pectin and are necessary
      for normal leaf cell enlargement and other growth processes.

PMID- 11509254
TI  - Taste: independent origins of chemoreception coding systems?
AB  - A large family of divergent candidate gustatory receptors has been identified in
      Drosophila. As with the odorant receptors, one receptor is expressed per sensory
      neuron, each class of which projects to discrete regions of the brain, allowing a
      combinatorial coding system for specific recognition of ligands.

PMID- 11509255
TI  - Protein synthesis: twenty three amino acids and counting.
AB  - The genetic code can be interpreted during translation as 21 amino acids and
      three termination signals. Recent advances at the interface of chemistry and
      molecular biology are extending the genetic code to allow assignment of new amino
      acids to existing codons, providing new functional groups for protein synthesis.

PMID- 11509256
TI  - Visual processing: parallel-er and parallel-er.
AB  - The mammalian visual system processes many different aspects of the visual scene
      in separate, parallel channels. Recent experiments suggest that the visual
      cortex, like the retina, forms parallel circuits even at very fine spatial
      scales.

PMID- 11509258
TI  - Mammalian phylogeny: genes and supertrees.
AB  - A massive effort to sample mammals for genes has yielded new proposals for the
      branching architecture of the great radiation of placental mammals. Some of these
      are notably discrepant with morphologically based analyses, but they suggest new
      research that should address several major outstanding issues.

PMID- 11509257
TI  - Cadherin function: breaking the barrier.
AB  - Three desmoglein isoforms collaborate with desmocollins to build the adhesive
      core of desmosomes. A recent study has shown that altering the ratio of
      desmoglein isoforms influences epidermal barrier function, suggesting distinct
      roles for these cadherins that extend beyond adhesion.

PMID- 11509259
TI  - Population genomics: linkage disequilibrium holds the key.
AB  - Current efforts to find disease-causing genes depend on patterns of linkage
      disequilibrium in human populations. Recent work has shown that linkage
      disequilibrium can extend over much larger genomic regions than expected, and
      that the patterns of linkage disequilibrium can differ markedly among
      populations.

PMID- 11509260
TI  - Video-assisted thoracic surgery major pulmonary resections. Present experience.
AB  - OBJECTIVE: The purpose of this report is to review our experience of video
      assisted thoracic surgery (VATS) major pulmonary resections. METHODS: From
      January 1993 to December 1999 we proposed VATS, for major pulmonary resections,
      with these indications: benign lesions and solitary metastases not removable by
      wedge resection and stage I non-small cell lung cancer (NSCLC). The maximum size
      of the lesion had to be less than 4 cm. RESULTS: There were 125 patients, 87 men
      and 38 women with a mean age of 62. We successfully performed VATS procedure in
      112 cases (one hamartoma, one tubercoloma, 12 typical carcinoids, 11 metastases
      and 87 lung cancers), while in another 13 (10.4%) a conversion to open surgery
      was required. There were 108 lobectomies, three bilobectomies and one
      pneumonectomy. Out of the first three cases of NSCLC, in all patients mediastinal
      node sampling or lymphadenectomy was performed. We recorded 13 (11.6%)
      postoperative complications, one of which required re-operation (bleeding). In
      the 99 patients without complications, the mean postoperative stay was 5.8 days.
      In a mean follow-up period of 36 months with patients having lung cancer we
      achieved a 3-year survival rate of 85+/-9 and 90+/-8% when only the patients in
      Stage I were considered. CONCLUSIONS: We believe that VATS, in performing
      pulmonary lobectomy, is a safe and effective approach and it seems to give the
      same long-term results as open surgery. Now the main problems concern the
      indications that should be strictly respected and the conversion to thoracotomy
      which should be undertaken without hesitation when the anatomic or pathologic
      conditions are not favourable.

PMID- 11509261
TI  - Thoracoscopic lobectomy for benign disease--a single centre study on 64 cases.
AB  - OBJECTIVE: Chronic lung infection is the main indication for lobectomy in benign
      pulmonary disease and may be technically demanding due to inflammatory changes
      such as adhesions, lymph node enlargement and neovascularization. The role of the
      thoracoscopic operation in these indications is yet ill-defined. METHODS: We
      retrospectively analyzed the results of patients who underwent thoracoscopic
      lobectomy (TL) between 1992 and June 1999 and compared this study group with
      patients who underwent open lobectomy (OL), all for benign disease. Data were not
      normally distributed, therefore, the median and range is given and nonparametric
      statistical analysis was applied. RESULTS: A total of 117 lobectomies for benign
      disease (64 TL) were analyzed. Indications included bronchiectasis (36 TL; 18
      OL), chronic infections (13 TL; eight OL), tuberculosis (five TL; 15 OL),
      emphysema (five TL; one OL), AV-malformations (two TL; one OL), severe
      haemoptysis (four OL), and others (three TL; six OL). Twelve conversions to
      thoracotomy were necessary due to severe adhesions. One patient in the open
      lobectomy group died within 30 days postoperative. Drainage time was 5.0 (1-32)
      days in TL and 6.0 (3-21) days in OL, hospital stay was 8.5 (4-41) days and 10.0
      (5-52) days, respectively. Blood loss was 0 (0-2000) ml in TL and 300 (0-6000) ml
      in OL. Operation time for thoracoscopic lobectomies significantly decreased from
      2.5 (1-6) h for cases between 1992 and 1997 (n=49) to 1.5 (0.5-2.5) h for recent
      cases (n=15) (P<0.01). In addition, a trend towards less blood loss was noted
      (100 (0-2000) ml vs. 0 (0-400) ml; P=0.06). Drainage time and hospital stay did
      not differ significantly. CONCLUSIONS: Thoracoscopic lobectomy in chronic
      inflammatory disease can be performed safely in selected patients, especially
      with bronchiectasis. Conversion rate to thoracotomy is low. Operation time with
      this approach declined significantly over time.

PMID- 11509262
TI  - One-day admission for major lung resections in septuagenarians and octogenarians:
      a comparative study with a younger cohort.
AB  - OBJECTIVES: The proportion of elderly patients presenting with a potentially
      resectable lung malignancy is increasing. Due to their greater operative risk,
      these patients are frequently offered a lesser resection, non-surgical treatment,
      or no treatment at all. The goal of this study is to determine whether
      septuagenarians and octogenarians undergoing video-assisted major lung resections
      benefit from an accelerated recovery program as much as younger patients,
      enabling them to be discharged after an overnight hospital stay. A short length
      of hospital stay, per se, does not represent the actual goal of this clinical
      care pathway. Instead, it should be considered as a measurement of how quickly
      functional ability is restored. METHODS: Of 65 consecutive patients who underwent
      major lung resections, 30 were 70 years of age or older (25 septuagenarians and
      five octogenarians; mean age, 75.7 years). Forty-six lobectomies, eight
      bilobectomies, and 11 pneumonectomies were performed using a video-assisted
      muscle-sparing minithoracotomy. In the elderly group, 24 lobectomies, three
      bilobectomies, and three pneumonectomies were performed. Patient and family
      education, multimodal analgesia, and an accelerated recovery program were
      implemented for all patients and the results were compared between the elderly
      group and the younger cohort. Discharge criteria included: (a), pain controlled
      with oral analgesics; (b), clear lungs in chest radiograph and without evidence
      of pneumothorax with the chest tube off suction; (c), independent ambulation;
      (d), adequate oxygenation; and (e), patient's acceptance and with home support.
      Whenever these criteria were met, regardless of how early or late during the
      hospital stay, the patient was released from the hospital. RESULTS: There were no
      deaths within 30 days of the operation and only three complications (one in the
      elderly group), and none of them altered the patients' clinical courses. The mean
      length of hospital stay for the whole group was 1.2 days (54 patients had an
      overnight hospital stay and two were outpatient procedures). The mean length of
      hospital stay for the elderly group was 1 day (27 patients had an overnight
      hospital stay and one was an outpatient procedure). None of the patients required
      conversion to a standard posterolateral thoracotomy and no patient required
      readmission related to an early discharge. CONCLUSIONS: These data show that it
      is feasible to create strategies to prevent or attenuate physiological
      derangements during surgery while performing major lung resections. As a result,
      an early recovery with few complications has been attained, allowing patients to
      consistently meet stringent discharge criteria after only an overnight hospital
      stay, even in the case of septuagenarians and octogenarians.

PMID- 11509263
TI  - Acute phase responses following minimal access and conventional thoracic surgery.
AB  - OBJECTIVES: Major thoracic surgery is associated with trauma-related
      immunological changes. These may impair anti-tumour immunity. We hypothesize that
      the reduced operative trauma associated with a video-assisted thoracic surgery
      (VATS) approach may decrease acute phase responses and, consequently, lead to
      better preservation of immune function. This prospective randomized study
      compared the effects of conventional open thoracic surgery and VATS on acute
      phase responses in patients undergoing pulmonary lobectomy. METHODS: Acute phase
      indicators were analyzed in patients undergoing lobectomy for suspected
      bronchogenic carcinoma. Surgery was prospectively randomized to pulmonary
      lobectomy by VATS or limited postero-lateral thoracotomy. Blood was taken pre
      operatively and at 4, 24, 48, 72, 120 and 168 h post-operatively for analysis of
      C-reactive protein (CRP; 41 patients: open, n=22; VATS, n=19) interleukin (IL)-6,
      tumour necrosis factor (TNF) receptors (TNF-sR55, TNF-sR75) and P-selectin (24
      patients: open, n=12; VATS, n=12). Samples taken at 48 and 168 h were also
      analyzed for phagocyte reactive oxygen species (ROS) production (25 patients:
      open, n=16; VATS, n=19). RESULTS: Surgery increased acute phase responses. VATS
      was associated with lower CRP and IL-6 levels. In the open surgery group,
      significant increases in ROS in neutrophils (up to 36% greater than before
      surgery, n=12, P<0.02-0.05) were detected at 2 days after surgery, but in the
      VATS group, the increase after surgery (of up to 17%, n=18) did not reach
      significance. Similarly, monocyte ROS increases of up to 25% in the mean ROS in
      the open surgery group and of up to 17% in the VATS group were detected on days 2
      and 7 after surgery. CONCLUSIONS: VATS pulmonary lobectomy is associated with
      reduced peri-operative changes in acute phase responses. This finding may have
      implications for peri-operative tumour immuno-surveillance in lung cancer
      patients.

PMID- 11509264
TI  - Endoscopic treatment of lung cancer invading the airway before induction
      chemotherapy and surgical resection.
AB  - OBJECTIVE: Many patients with advanced lung cancer invading the airway require
      only palliation; however, induction chemotherapy and surgery may sometimes be
      considered. Preliminary endoscopic palliation may improve quality of life and
      functional status, allows better evaluation of tumor extension and contributes to
      prevent infectious complications. We reviewed our experience with preliminary
      laser treatment, induction chemotherapy and surgical resection in patients with
      lung cancer invading the airway. METHODS: Twenty-one patients with stage IIIA and
      IIIB lung cancer presenting with an 80% unilateral airway obstruction were
      treated with laser resection, induction chemotherapy and surgery. Spirometry,
      arterial blood gas analysis, quality of life (QLQ-C30 score) and performance
      status were recorded before and after laser treatment and after chemotherapy.
      Complications during chemotherapy, surgical morbidity and mortality, and survival
      were also recorded. RESULTS: No complications were observed after endoscopic
      treatment. FEV(1) significantly improved from 1.4+/-0.4 l/s to 2.2+/-0.7 l/s, as
      well as FVC (from 2+/-0.5 to 3.1+/-0.8 l), and remained stable after
      chemotherapy. The QLQ-C30 score significantly improved after laser treatment
      (from 45+/-4.8 to 31+/-2.5) as well as the Karnofsky status (from 76+/-5 to 90).
      One patient developed pneumonia during induction chemotherapy. Three patients
      were not operated on. We performed five pneumonectomies (one right tracheal
      sleeve pneumonectomy) and 13 lobectomies (five associated to a bronchial sleeve
      resection). One patient (5.5%) died after the operation. Four patients
      experienced minor postoperative complications. Three-year survival after the
      operation was 52%. CONCLUSIONS: Preliminary endoscopic palliation of lung cancer
      invading the airway is feasible, improves evaluation and staging, helps to reduce
      the incidence of complications during induction chemotherapy without increasing
      surgical morbidity and mortality.

PMID- 11509265
TI  - PET-FDG scan enhances but does not replace preoperative surgical staging in non
      small cell lung carcinoma.
AB  - OBJECTIVE: To assess the effectiveness of positron emission tomography with
      radiolabeled [18F]-2-fluoro-deoxy-D-glucose (PET-FDG) imaging in mediastinal
      lymph node (LN) staging for non-small cell lung carcinoma (NSCLC) and to compare
      it to conventional clinical and surgical staging. METHODS: From June 1998 to
      February 2000, we enrolled 64 potentially resectable NSCLC patients in a
      prospective study of PET-FDG imaging of the mediastinum to assess LN involvement.
      Results of this technique were compared to conventional clinical and surgical
      staging. Diagnostic efficacy was determined by calculating sensitivity,
      specificity, overall accuracy, and positive and negative predictive values for
      each method. RESULTS: PET-FDG imaging correctly identified nodal stage (N0-N1 vs.
      N2) in 50 out of 61 patients (82%), overstaging occurred in eight patients (13%),
      and understaging in three patients (4.9%). The sensitivity, specificity,
      accuracy, and positive and negative predictive values for PET-FDG scan imaging
      were 67, 85, 82, 43, and 93.6%, respectively. Conventional staging correctly
      identified nodal stage (N0-N1 vs. N2) in 51 out of 62 patients (82%), overstaging
      occurred in five patients (8.1%), and understaging in six patients (9.7%). The
      sensitivity, specificity, accuracy, and positive and negative predictive values
      for conventional staging were 33, 90.6, 82, 37, and 89%, respectively. With
      regard to N2 disease, conventional staging showed a poor sensitivity (33%).
      Indeed, six out of 64 patients were understaged for mediastinal LN involvement.
      Even though the improvement was not statistically significant (McNemar P=0.08),
      the combined use of PET-FDG scan and computerized tomography (CT) scan allowed a
      two-fold increase in the sensitivity of our clinical preoperative staging.
      Moreover, relying on the PET-scan high negative predictive value might have
      contributed to a three-fold decrease in the number of required surgical staging
      procedures. CONCLUSIONS: Our study shows that the PET-FDG imaging strength lies
      in its very high negative predictive value and increased sensitivity. In this
      study, the overall accuracy of PET-FDG scan (82%) was lower than previously
      reported. Combined with chest CT-scan preoperatively, it may alleviate the need
      for surgical staging when PET-FDG studies of the mediastinum are negative.
      However, with a positive PET-FDG scan result, further diagnostic procedures
      should be pursued in order to avoid overstaging and allow better surgical patient
      selection.

PMID- 11509266
TI  - Pneumonectomy for non-small cell lung cancer: predictors of operative mortality
      and survival.
AB  - OBJECTIVE: The purpose of this study was to identify predictors of operative
      mortality and survival following pneumonectomy for non-small cell lung cancer
      (NSCLC). METHODS: All 206 patients having a pneumonectomy for NSCLC between 1991
      and 1997 in our unit were prospectively studied. There were 162 males (79%) and
      44 females (21%) with a mean age (+/- standard deviation) of 61+/-7.7 years
      (range 34-81 years). Squamous cell (75%) and adenocarcinoma (17.0%) were the
      predominant histological types. The possible impact of 29 parameters on operative
      mortality and survival was tested with univariate and multivariate analysis. The
      mean follow-up was 2.3+/-1.2 years, ranging between 0 and 6.8 years, and it was
      complete. RESULTS: Operative mortality was 6.8% (14 deaths). On multiple logistic
      regression older age (P=0.04) and the development post-operatively of
      bronchopleural fistula (BPF) (P=0.01) were independent predictors of operative
      mortality. The overall, Kaplan-Meier, 1-, 3- and 5-year survival (+/- standard
      error from the mean), inclusive of operative mortality, was 68+/-3.3, 42+/-4.1
      and 35+/-4.5%. On Cox proportional hazards regression adenocarcinoma (P=0.006),
      the development of BPF (P=0.003), older age (P=0.03) and higher pathological
      stage (P=0.02) were independent adverse predictors of survival. CONCLUSION:
      Pneumonectomy for NSCLC carries a considerable, but acceptable, operative
      mortality and provides an important survival benefit. This study suggests that
      older age and BPF are major determinants of an unfavourable in-hospital outcome;
      older age, BPF, adenocarcinoma cell type and higher pathological stage
      significantly reduce the probability of a long-term survival.

PMID- 11509267
TI  - Bone marrow micrometastasis might not be a short-term predictor of survival in
      early stages non-small cell lung carcinoma.
AB  - OBJECTIVE: To determine the presence of occult micrometastasis (OM) in a selected
      population of surgically resectable patients presenting with non-small cell lung
      carcinoma (NSCLC) and to evaluate its prognostic value on relapses and survival.
      METHODS: From February 1996 to December 1999, 99 patients undergoing surgical
      treatment for NSCLC were prospectively investigated for the presence of occult
      bone marrow micrometastasis. Tumor cells were detected with monoclonal primary
      antibodies directed against low molecular weight cytokeratins. RESULTS: Median
      follow-up time was 14.3 months (range 0.2-45.6 months). Overall prevalence of OM
      was 22.2% (22 out of 99). The presence of OM was not correlated to pathology, T
      status, or N status. In survival analysis, the only independent predictors of
      overall survival were N0 status and Stage I (P=0.016 and 0.004, respectively),
      while T1 was a predictor of disease-free survival (P=0.044). Metastasis and loco
      regional recurrence were observed at follow-up in 18.2 (four out of 22) and 9%
      (two out of 22) of patients OM(+) and in 14.3 (11 out of 77) and 7.8% (six out of
      77) of patients OM(-), respectively (P=not significant). OM was a predictor
      neither of overall survival nor of disease-free survival (P=0.52 and 0.97,
      respectively). In Stage I patients, 1-year overall survival and 1-year disease
      free survival were 89 and 98% for OM(-) patients and 88 and 90% for OM(+)
      patients, respectively (P=0.57 and P=0.75). CONCLUSIONS: OM was present in >20%
      of surgically treated NSCLC patients and did not correlate to pathological
      variables. In contrast to previous published data, in this study the presence of
      OM had no influence on overall or disease-free survival.

PMID- 11509268
TI  - Surgical results for multiple primary lung cancers.
AB  - OBJECTIVE: The development of a multiple primary lung cancer (MPLC) is not rare
      in long-term survivors after curative resections. We analysed our experience in
      order to verify surgical results and long-term survival in our patients. METHODS:
      From 1971 to 1999, 80 patients with MPLC (two tumours each, total 160) were
      treated at the Division of Thoracic Surgery of the University of Padua. Our
      criteria for the definition of a synchronous or metachronous cancer are those
      proposed by Martini and Melamed. We had 19 patients with a synchronous tumour and
      61 patients with a metachronous tumour. We performed 95 lobectomies, 5 completion
      pneumonectomies and 53 segmentectomies. Of 160 MPLCs, 60 were squamous
      carcinomas, 78 adenocarcinomas, 8 small cell lung cancers, 9 large cell lung
      cancers and 5 other tumours. Of 160 MPLCs, 140 were N0 disease (87.5%) and 20
      were N1 or N2 disease (12.5%). RESULTS: The overall 30-day mortality was 2.5% (2
      patients). Eighteen patients (22.5%) had postoperative complications. Survival at
      5 and 10 years for all patients was 72% and 58%, respectively. Five-year survival
      for patients with metachronous and synchronous disease from the time of initial
      diagnosis of cancer was 85% and 20% (P=0.001), and 10-year survival was 58% and
      0% (P=0.001), respectively. Survival after the development of a metachronous
      lesion was 51% at 5 years and 20% at 10 years. The 5-year survival of patients
      with metachronous tumours undergoing standard surgical procedures of the second
      tumour was 52%; the 5-year survival of patients undergoing atypical or segmental
      resections was 55%. CONCLUSIONS: Careful follow-up is recommended in all patients
      surviving curative resection. More accurate selection criteria for MPLC is
      required. An aggressive surgical approach is justified in patients with MPLC and
      offers the greatest chance for long-term survival even in the case of limited
      resection.

PMID- 11509269
TI  - Pulmonary function testing after operative stabilisation of the chest wall for
      flail chest.
AB  - OBJECTIVE: This is a prospective evaluation of chest wall integrity and pulmonary
      function in patients with operative stabilisation for flail chest injuries.
      METHODS: From 1990 to 1999, 66 patients (56 men, 10 women; mean age 52.6 years)
      with antero-lateral flail chest (> or =4 ribs fractured at > or =2 sites)
      underwent surgical stabilisation using reconstruction plates. Clinical assessment
      and pulmonary function testing were performed at 6 months following surgery.
      RESULTS: Fifty-five (83%) patients had various combinations of injuries of the
      thorax, head, abdomen and extremities. Sixty-three (95.5%) patients underwent
      unilateral and 3 (4.5%) patients bilateral stabilisation with a median delay of
      2.8 days (range 0-21 days) from admission. The 30-day mortality was 11% (seven of
      66 patients). Immediate postoperative extubation was feasible in 31 of 66
      patients (47%) and extubation within 7 days following stabilisation in 56 of 66
      patients (85%). No plate dislocation was observed during the follow-up. The
      shoulder girdle function was intact in 51 of 57 patients (90%). Chest wall
      complaints were noted in 6 of 57 (11%) patients, requiring removal of implants in
      three cases. All patients returned to work within a mean period of 8 (range 3-16)
      weeks following discharge. Pulmonary function testing (n=50) at 6 months after
      the operation revealed a significant difference of predicted vs. recorded vital
      capacity (VC) and forced expiratory volume in 1s (FEV1) (P=0.04 and P=0.0001,
      respectively; Wilcoxon signed-rank test). The median ratio of the recorded and
      predicted total lung capacity (TLC) was shown to be significantly higher than
      0.85 (P=0.0002; Wilcoxon signed-rank test), indicating prevention of pulmonary
      restriction. CONCLUSION: Antero-lateral flail chest injuries accompanied by
      respiratory insufficiency can be effectively stabilised using reconstruction
      plates. Early restoration of the chest wall integrity and respiratory pump
      function may be cost effective through the prevention of prolonged mechanical
      ventilation and restriction-related working incapacity.

PMID- 11509270
TI  - Effects of cryoanalgesia on post-thoracotomy pain and on the structure of
      intercostal nerves: a human prospective randomized trial and a histological
      study.
AB  - OBJECTIVE: The choice of analgesia in the management of post-thoracotomy pain
      remains controversial. Although several alternative forms of post-thoracotomy
      analgesia exist, all have their disadvantages. Cryoanalgesia, localized freezing
      of intercostal nerves, has been reported to have variable effectiveness and an
      incidence of long-term cutaneous sensory changes. We carried out an animal study
      to assess the reversibility of histological changes induced by cryoanalgesia and
      a prospective randomized trial to compare the effectiveness of cryoanalgesia with
      conventional analgesia (parenteral opiates). METHODS: In six anaesthetized dogs,
      intercostal nerves were exposed to a varying duration of cryo-application (30,
      60, 90 and 120 s). The nerves were biopsied and examined histologically at
      regular intervals over the following 6 months. In the clinical study, 200
      consecutive patients undergoing thoracotomy were randomized to cryoanalgesia and
      conventional (parenteral opiates) analgesia groups. Postoperative pain scores,
      respiratory function tests and use of opiate analgesia were measured for the two
      groups. RESULTS: Following application of the cryoprobe, degeneration and
      fragmentation of the axons was evident with associated inflammatory changes. As
      the endoneurium remained intact, axonal regeneration took place after the
      resolution of axonal swelling. Over the course of weeks, recovery of the
      intercostal nerve occurred and was complete after 1 month for the 30 and 60 s
      groups. For nerves exposed to longer durations of cryoanalgesia, the time taken
      for complete recovery was proportionally increased. Clinically, there was a
      statistically significant (P<0.05) improvement in postoperative pain scores and
      use of opiate analgesia and an improvement (P>0.05) in respiratory function tests
      for patients in the cryoanalgesia group. The previously suggested cutaneous
      sensory changes resolved within 6 months with complete restoration of function.
      CONCLUSIONS: We suggest that cryoanalgesia be considered as a simple,
      inexpensive, long-term form of post-thoracotomy pain relief, which does not cause
      any long-term histological damage to intercostal nerves.

PMID- 11509271
TI  - Survival and graft function in a large animal lung transplant model after 30 h
      preservation and substitution of the nitric oxide pathway.
AB  - OBJECTIVE: Substitution of the nitric oxide- (NO-) pathway improves early graft
      function following lung transplantation. We previously demonstrated that 8-Br
      cGMP (second messenger of NO) to the flush solution and tetrahydrobiopterin (BH4,
      coenzyme of NO synthase) given as additive during reperfusion improve post
      transplant graft function. In the present study, the combined treatment with 8-Br
      cGMP and BH4 was evaluated. METHODS: Unilateral left lung transplantation was
      performed in weight matched outbred pigs (24-31 kg). In group I, grafts were
      preserved for 30 h (n=5). 8-Br-cGMP (1mg/kg) was added to the flush solution
      (Perfadex, 1.5l, 1 degrees C) and BH4 (10mg/kg/h) was given to the recipient for
      5h after reperfusion. In group II, lungs were transplanted after a preservation
      time of 30 h (n=3) and prostaglandin E(1) (250 g) was given into the pulmonary
      artery (PA) prior to flush. In all recipients 1h after reperfusion the
      contralateral right PA and bronchus were ligated to assess graft function only.
      Survival time after reperfusion, extravascular lung water index (EVLWI),
      hemodynamic variables, and gas exchange (PaO(2)) were assessed during a 12h
      observation period. RESULTS: All recipients in group I survived the 12h
      assessment, whereas none of the group II animals survived more than 4h after
      reperfusion with a rapid increase of EVLWI up to 24.8+/-6.7 ml/kg. In contrast,
      in group I EVLWI reached up to 8.9+/-1.5 ml/kg and returned to nearly normal
      levels at 12h (6.1+/-0.8 ml/kg). In two animals of group I the gas exchange
      deteriorated slightly. The other three animals showed normal arterial oxygenation
      over the entire observation time. CONCLUSION: Our data indicate that the combined
      substitution of the NO pathway during preservation and reperfusion reduces
      ischemia/reperfusion injury substantially and that this treatment even allows
      lung transplantation after 30 h preservation in this model.

PMID- 11509272
TI  - Endovascular stent-graft treatment for diseases of the descending thoracic aorta.
AB  - OBJECTIVE: Assessment of endovascular stent-graft treatment for diseases of the
      descending thoracic aorta as a valid and effective alternative to surgery.
      METHODS: From March 1999 to August 2000, a total of 16 patients underwent
      deployment of endovascular stent-grafts in the descending thoracic aorta.
      Patients were divided into three groups according to the type of lesion. Group A
      (n=8) included five patients with atherosclerotic aneurysm and three with chronic
      post-traumatic pseudoaneurysm. Patients with acute post-traumatic pseudoaneurysm
      (n=3) and type B aortic dissection (n=5) were included in Groups B and C,
      respectively. All patients underwent 5-mm chest spiral angio-computerized
      tomography (CT) scan and angiography as preoperative assessment. The deployed
      stent-graft systems were Talent-Medtronic and Excluder-Gore. RESULTS: A total of
      20 stent-grafts were placed. Two patients required deployment of two grafts,
      while three grafts were juxtaposed in a third patient in order to treat larger
      lesions. There was no mortality related to the procedure, although one patient
      (6.2%) died because of multiorgan failure 24h post-operatively. The placement of
      the graft was successful in all cases except one affected with type B dissection
      and characterized by a very large intimal flap, which was eventually fenestrated
      by graft guidewire. Therefore, an optimal sealing of the grafts was achieved in
      15 patients. However, in one patient the descending aorta had to be surgically
      replaced because of the calcified pseudoaneurysm still compressing the trachea
      and left bronchus. Two patients required a left carotid-subclavian by-pass in
      order to achieve a sufficient neck for the proximal placement of the graft. No
      spinal cord injuries were observed. At the follow-up, performed with chest spiral
      angio-CT scan within 72 h and scheduled at 6 and 12 months and once a year, no
      stent-graft related complications have been detected. CONCLUSIONS: Endoluminal
      stent-graft treatment may represent a valid option in well-selected cases of
      descending thoracic aorta diseases. A longer follow-up in a larger series of
      patients is desirable to confirm these initial positive results.

PMID- 11509273
TI  - Surgical treatment of thoracoabdominal aortic aneurysm after repairs of
      descending thoracic or infrarenal abdominal aortic aneurysm.
AB  - OBJECTIVE: The outcome of thoracoabdominal aortic aneurysm repair after
      operations for descending thoracic or infrarenal abdominal aortic aneurysm was
      investigated. METHODS: Between May 1982 and July 2000, 102 patients underwent
      thoracoabdominal aortic aneurysm repair. Of these patients, 36 had previously
      undergone operations for descending thoracic or abdominal aortic aneurysm. To
      evaluate the influence of previous descending thoracic or infrarenal abdominal
      aortic aneurysm repair on the results of TAAA replacement, patients were divided
      into two groups: one group of patients who had previously undergone descending
      thoracic or infrarenal abdominal aortic aneurysm repair (group I, n=36) and one
      group of patients who had not previously undergone descending thoracic or
      infrarenal abdominal aortic aneurysm repair (group II, n=66). RESULTS: Patients
      with previous descending thoracic or infrarenal abdominal aortic aneurysm repair
      had more chronic dissection and extensive thoracoabdominal aortic aneurysm. The
      distal aortic perfusion time and total aortic clamp time were both longer in
      group I. The total selective visceral and renal perfusion time and operation time
      did not differ significantly between the two groups. In 30-day mortality rates
      were 5.5% in group I and 13% in group II. Major postoperative complications
      included paraplegia in 14% of patients in group I and 3.1% in group II, renal
      failure requiring hemodialysis in 22% of patients in group I and 19% of patients
      in group II, respiratory failure in 36% of patients in group I and 30% of
      patients in group II, postoperative hemorrhage in 11% of patients in group I and
      16% of patients in group II. CONCLUSION: The presence of a previous descending
      thoracic or infrarenal abdominal aortic aneurysm did not adversely affect the
      outcome of thoracoabdominal aortic aneurysm repair.

PMID- 11509274
TI  - Doppler ultrasonographic identification of the critical segmental artery for
      spinal cord protection.
AB  - OBJECTIVE: The purpose of this study is to evaluate the possibility of
      identifying critical segmental arteries (CSAs) based on Doppler ultrasonographic
      hemodynamics. METHODS: In 18 mongrel dogs, the descending aorta was scanned
      directly with a 5-MHz linear probe through left thoracotomies and the flow
      velocities in segmental arteries were measured by pulsed Doppler. The aorta was
      cross-clamped between Th13 and L1, and flow velocity changes were recorded.
      According to flow increases, segmental arteries were divided into three groups:
      arteries with the largest flow increase (L-arteries), arteries with the smallest
      increase (S-arteries) and other arteries (O-arteries). Animals were divided into
      three groups. One aortic segment including an L-artery or an S-artery was
      perfused via a temporary shunt during 30-min aortic cross-clamping distal to the
      left subclavian artery (Group L or Group S) and neurological outcomes were
      compared with those of animals without shunting (Group N) after 24 and 48 h.
      RESULTS: L-arteries had significantly larger flow increases than S- and O
      arteries (74.3+/-33.8, 20.4+/-9.8 and 33.3+/-17.8 cm/s, P<0.01). In Group N, five
      of the six animals were completely paraplegic (Tarlov Grade 0) and the other was
      Grade 1. In Group S, four animals were Grade 4 and two were Grade 0 after 24h.
      However, two animals showed delayed paraplegia. Therefore, four animals were
      Grade 0 and two were Grade 4 after 48 h. All animals in Group L were
      neurologically normal (Grade 4) at both after 24h (vs. Group N, P=0.0013) and 48
      h (vs. Group N, P=0.0013; vs. Group S, P=0.019). CONCLUSIONS: Flow responses to
      aortic cross-clamping differed among segmental arteries and selective perfusion
      of L-arteries completely prevented paraplegia. Therefore, L-arteries were
      considered to be CSAs. Hemodynamic measurement of segmental arterial flow using
      Doppler ultrasonography could be clinically useful for spinal cord protection
      during thoracoabdominal aortic surgery.

PMID- 11509275
TI  - OPCAB surgery: a critical review of two different categories of pre-operative
      ejection fraction.
AB  - OBJECTIVE: Literature review found little information on off-pump coronary artery
      bypass (OPCAB) procedure in patients with poor left ventricular function and
      there was no information comparing the low EF and normal EF patients undergoing
      OPCAB procedure. METHODS: Between 1/1/1998 and 6/30/1999, 387patients had surgery
      performed utilizing the off-pump technique and 45 of these patients had pre
      operative left ventricular function of equal to or less than 30% (LVEF < or =30).
      The two groups (LVEF < or =30 and LVEF>30) were compared using univariate
      analysis. Patients in LVEF < or =30 were older and more female gender. LVEF< 30
      had more NYHA class IV patients (64 vs. 50%) and more symptoms related to
      depressed left ventricular function. The mean pre-operative left ventricular
      function was 25% in LVEF < or =30 and 56% in LVEF>30. Pre-operative predicted
      risk was 6.4+/-5.5% in LVEF < or =30 and 2.7+/-4.5% in LVEF>30 (P< 0.001). Most
      (> 95%) of the patients in both groups were elective status, and LVEF < or =30
      patients had increased incidence of redo (11 vs. 6%, P=0.2). In LVEF>30, 84% of
      the patients had stable angina while only 69% in LVEF < or =30 (P=0.009).
      RESULTS: Intra-operatively no significant differences were measured in number of
      grafts per patient (2.7 vs. 2.8), amount of blood loss, peak CK-MB, skin-to-skin
      time, or OR time. Patients with LVEF < or =30 have more frequent utilization IABP
      during pre, intra and post-operative period. The statistical analysis yields no
      significance in post-operative major neurological deficit between these two
      groups; and are comparative to the nationally reported incidence of neurological
      deficit for on-pump patients. The operative mortality in the low EF group was 4.4
      and 1.8% in LVEF>30 group (P=0.23). CONCLUSIONS: Given the clinical presentation
      of the low EF group, higher prediction risk, longer pre-operative stay, and
      length of ventilation (24 vs. 8 h P=0.12) a longer surgery to discharge stay (8
      vs. 6 days, P=0.02) is anticipated. Short-term clinical outcomes for both groups
      of OPCAB patients encouraged us to continue to offer this approach to this broad
      base of patient population.

PMID- 11509276
TI  - The challenge of departmental quality control in the reengineering towards off
      pump coronary artery bypass grafting.
AB  - OBJECTIVE: Off pump coronary surgery is a major reengineering effort of the
      surgical systems. There are no perfect tools available to guide every centre in
      the confrontation with the complete spectrum of risk and the limited number of
      events. This study analyses the use of a hospital mortality risk-stratifying
      system in the complete shift towards off-pump CABG. METHODS: All 535 off-pump
      CABG patients from January 1997 till September 2000 underwent a comparison of
      their hospital mortality versus the EuroSCORE predictions. The mean risk
      predicted by the EuroSCORE was 4.5+/-3% (range 0-14) and the mean age was 65+/-10
      years (range 36-89). The series includes 23 repeat procedures, also 77 patients
      with per oral or insulin-treated diabetes. The number of distal anastomoses was
      2.5+/-1 and of arterial grafts 1.3+/-0.6. RESULTS: The observed hospital
      mortality was 15 patients, 2.8% (Fisher exact test P=0.19 versus the EuroSCORE).
      The 1 and 3 month Kaplan-Meier survival, irrespective from hospital discharge,
      was 97.4+/-0.7 and 97.2+/-0.7%, respectively. A cumulative risk-adjusted
      mortality plot is constructed. The area under the ROC curve was 0.886. A stepwise
      sampling of patients according to increasing risk identified the difference
      between the EuroSCORE-predicted and observed hospital mortality for the complete
      spectrum of risk. The P value of this difference was 0.06 for the grouping
      including all patients from 0-5% risk (78% reduction), 0.04 for the grouping 0-8%
      risk (61% reduction), and 0.05 for the grouping 0-11% risk (52% reduction of
      risk). The loss of statistical significant difference was due to the inclusion of
      the patients at extremely high risk. CONCLUSION: A hospital mortality risk
      stratifying system can provide guidance but different and in depth approaches are
      mandatory to improve the insight, certainly in the presence of a large spectrum
      of risk.

PMID- 11509277
TI  - Predictive value of perioperative cardiac troponin I for adverse outcome in
      coronary artery bypass surgery.
AB  - OBJECTIVES: Cardiac Troponin I (cTnI) is a well-known marker for myocardial
      damage in patients undergoing aorto-coronary bypass grafting (CABG) peaking 6-8 h
      after aortic declamping. The aim of this study was to evaluate cTnI release in
      the course of CABG procedures early, i.e. after the cessation of cardiopulmonary
      bypass (CPB) in order to recognize unstable cardiac function leading to
      hemodynamic deterioration and resulting in an adverse outcome (AO). AO is defined
      as the onset of myocardial infarction and/or death peri/postoperatively. METHODS:
      Five-hundred and forty consecutive patients who underwent CABG were evaluated for
      cTnI release immediately prior to the induction of anesthesia (IND) and after
      termination of CPB (END). Standard CPB with ante/retrograde cold blood
      cardioplegia was used. Patients with any of the following criteria were excluded:
      (1), CABG within 7 days of myocardial infarction; (2), emergency operation for
      both unstable angina and for coronary occlusion at angioplasty; (3), CABG with
      concomitant surgical cardiac procedures; (4), preoperative renal dysfunction
      requiring hemodialysis; (5), redos. Troponin I was measured with the Stratus CS
      fluorometric enzyme immunoassay analyzer (Dade-Behring) running on site in the
      operation room (OR), so values of cTnI could be obtained within 15 min. RESULTS:
      There were six deaths (1.1%) in the entire series, Q-wave myocardial infarction
      occurred in 19 patients (3.5%), AO was experienced by 21 patients (3.9%). The
      mean preoperative cTnI level was 0.04+/-0.17 ng/l (mean+/-standard deviation) for
      the entire group. The END cTnI level for the AO-group was 0.91+/-0.5 ng/l; for
      all other patients, this was 0.37+/-0.3 ng/l (P<0.001). Changes in intraoperative
      cTnI levels relative to time course showed a marked increase for the AO-group
      (0.0038+/-0.0035 ng/l*min) as compared with non-AO patients (0.0019+/-0.0015
      ng/l*min; P=0.028). The receiver operating characteristic curve indicates a cTnI
      level at CPB-end of higher than 0.495 ng/l with an area under the curve of 0.83
      as the optimal cut-off point for predicting AO with a sensitivity and specificity
      of 76.2%. Stepwise logistic regression analysis revealed END cTnI level (odds
      ratio, 17.24; P<0.001), CPB time (odds ratio, 1.03; P=0.001), female sex (odds
      ratio, 3.8; P=0.011) as significant independent predictors for AO. Age of over 70
      years (P=0.8), Cleveland Clinic risk score (P=0.65), diabetes (P=0.26), elevated
      preoperative creatinine level (P=0.77), severe left ventricular dysfunction
      (P=0.51), the number of grafts performed (P=0.15), and change of intraoperative
      cTnI level relative to time course (P=0.94) did not reach statistical
      significance. CONCLUSIONS: cTnI release as determined at the end of CABG
      procedures represents a strong predictor of an AO after surgery. Analyzing blood
      samples for cTnI with an automated device on site in the OR provides for
      immediate results, so specific diagnostic and therapeutic interventions can be
      performed before hemodynamics deteriorate.

PMID- 11509278
TI  - IL-8 concentration in coronary sinus blood during early coronary reperfusion
      after ischemic arrest.
AB  - OBJECTIVE: Activation of the inflammatory response is an important factor
      contributing to complications of cardiopulmonary bypass. Increased level of
      proinflammatory cytokine - IL-8 has been reported during coronary artery bypass
      grafting (CABG) operations with the use of cardiopulmonary bypass. The aim of
      this study was to find out whether the heart is the main source of IL-8 during
      early coronary reperfusion. METHODS: IL-8 concentration in coronary sinus before
      clamping and 5, 10, and 15 min after declamping of the aorta as well as in radial
      artery blood before clamping and 10 min after declamping of the aorta, was
      assessed in 30 patients undergoing CABG surgery. RESULTS: We observed increase in
      IL-8 concentration in coronary sinus blood after declamping of the aorta, however
      no difference between coronary sinus and arterial blood concentration was noted.
      The median value of IL-8 concentration in coronary sinus blood was 1.85 pg/ml
      before ischemia and 15.4, 20.3, and 29.3 pg/ml in 5, 10 and 15 min after aortic
      declamping, respectively. Our additional finding was that there was a negative
      correlation between IL-8 level and hemoglobin saturation with oxygen in coronary
      sinus blood 10 min after coronary reperfusion. CONCLUSIONS: We conclude that the
      heart is not the main source of IL-8 in early coronary reperfusion, although
      coronary reperfusion induces its release.

PMID- 11509279
TI  - Cardiac dysfunction and inefficiency after substrate-enriched warm blood
      cardioplegia.
AB  - OBJECTIVE: The study assessed the outcome after prolonged warm continuous
      antegrade blood cardioplegia (WCBC) with substrate enrichment, in terms of
      mechanical performance and mechanoenergetic efficiency. METHODS: WCBC was given
      for 3 h to three groups of pigs on cardiopulmonary bypass; WCBC alone (n=7),
      WCBC+glucose and insulin (+GIK, n=7) and WCBC+L-glutamine (+GLN, n=7). Cardiac
      systolic and diastolic function, pressure-volume area (PVA) and myocardial oxygen
      consumption (MVO(2)) were assessed before, and twice after WCBC using pressure
      conductance catheter, coronary flow-probes and O(2)-content difference. RESULTS:
      In the WCBC, +GIK and +GLN groups respectively, the following parameters
      decreased after WCBC compared to baseline: left ventricular developed pressure by
      26, 19 and 25% (P<0.001); dP/dt(max) by 36, 37 and 34% (P<0.001); preload
      recruitable stroke work by 35, 41 and 28% (P<0.001); mechanoenergetic efficiency
      (PVA/MVO(2)) by 44, 41 and 22% (P<0.001). End-diastolic stiffness increased early
      after WCBC in the WCBC and +GLN groups, while it was unchanged in the +GIK group
      (P=0.032). CONCLUSION: Despite continuous aerobic conditions and additional
      substrates, post-WCBC cardiac contractile function and mechanoenergetic
      efficiency was severely depressed. The results demonstrate the hazards of
      sustained normothermic hyperkalemic perfusion.

PMID- 11509280
TI  - Coronary artery bypass grafting for patients with non-dialysis-dependent renal
      dysfunction (serum creatinine > or =2.0 mg/dl).
AB  - INTRODUCTION: Patients with renal dysfunction carry a risk of coronary
      atherosclerosis. The purpose of this study was to evaluate the outcome after
      coronary artery bypass grafting (CABG) in patients with decreased renal function
      (serum creatinine > or =2.0 mg/dl). METHODS: We retrospectively analyzed
      consecutive patients who had undergone isolated CABG at Shin-Tokyo Hospital
      between May 1, 1991 and April 31, 2000. Preoperative, perioperative, and follow
      up data of the non-dialysis-dependent patients with preoperative serum creatinine
      equal to or more than 2.0mg/dl (group R, n=59) were collected, and compared with
      those of the control patients (serum creatinine < 2.0, group C, n=1666). Group R
      was further divided into the off-pump and on-pump CABG group and their
      perioperative results were compared. RESULTS: Group R included 51 males and eight
      females with a mean age of 66.4. The mean number of anastomoses was not
      significantly different between groups; however, clump time and pump time were
      longer in group R. Postoperative recovery was longer in group R than in group C,
      which is associated with a more frequent occurrence of major complications (28.8%
      in group R and 10.7% in group C, P<0.0001) and mortalities (6.8% in group R and
      0.5% in group C, P<0.0005). The patients who underwent off-pump CABG experienced
      relatively faster recovery than those who underwent on-pump CABG, despite
      decreased renal function. At the mean follow-up of 2.4 years, the actuarial 3
      year survival rate of groups R and C were 75.3 and 96.9%, respectively
      (P<0.0001), excluding hospital mortality. The actuarial 3-year cardiac event-free
      rate was 76.7% in group R and 87.3% in group C (P<0.05). CONCLUSIONS: Patients
      with decreased renal function carry significant operative risks and require
      prolonged hospital care. Even after adequate surgical revascularization was
      completed, the long-term cardiac event-free and survival rates in the patients
      with renal dysfunction were inferior to the patients with normal renal function.

PMID- 11509281
TI  - Primary spontaneous coronary artery dissections in atherosclerotic patients.
      Report of nine cases with review of the pertinent literature.
AB  - Primary spontaneous coronary artery dissection is one of the rare causes of acute
      myocardial infarction. Previous studies reports that it is mostly seen in middle
      aged women in the last trimester of pregnancy and early postpartum period.
      Clinical presentation of the disease is variable in pattern and severity related
      to extent and development rate of dissection. In the last 2 years, nine non
      pregnant primary spontaneous coronary artery dissection cases were found in
      coronary angiography among 3750 patients prediagnosed as coronary artery disease.
      The cases were presented and discussed with review of the pertinent literature.

PMID- 11509282
TI  - Tricuspid valve surgery for functional tricuspid valve regurgitation associated
      with left-sided valvular disease.
AB  - OBJECTIVES: We have reviewed 260 patients who underwent initial tricuspid valve
      surgery for functional tricuspid valve regurgitation (TR) and analyzed
      independent predictors for early and late unfavorable results. MATERIALS AND
      METHODS: Between 1981 and 1998, 260 tricuspid valve operations were performed for
      functional TR. There were 94 males and 166 females with a mean age of 55 years.
      The tricuspid valve surgery procedures consisted of De Vega tricuspid
      annuloplasty in 240 patients, ring annuloplasty in four patients, and tricuspid
      valve replacement in 16 patients. The mean duration of follow-up was 7.8 years.
      RESULTS: Hospital mortality was 8.9% (23 patients). Late deaths occurred in 34
      patients including cardiac-related late deaths in 26 patients. The survival rates
      were 83+/-2% at 5 years and 78+/-3% at 10 years. Late tricuspid valve reoperation
      was performed on 13 patients due to residual or recurrent TR in 12 patients and
      thrombosed tricuspid bileaflet mechanical valve in one patient. The tricuspid
      valve reoperation-free survival rate was 90+/-2% at 5 years and 84+/-3% at 10
      years. The only predictor of hospital mortality was preoperative highly elevated
      right atrial pressure (P=0.01). Variables predictive of cardiac-related late
      death were preoperative New York Heart Association (NYHA) class IV (P=0.01) and
      poor left ventricular ejection fraction (LVEF) (P=0.02). Residual TR of more than
      grade 2+ early after tricuspid annuloplasty was a significant risk factor for
      late tricuspid valve reoperation (P=0.01). Preoperative TR of grade 4+ was
      predictive of early residual TR (P=0.04). CONCLUSIONS: Tricuspid valve surgery
      for functional TR can be performed with acceptable levels of early mortality.
      Cardiac-related late mortality after tricuspid surgery may be improved by earlier
      surgical treatment before NYHA class IV or deterioration of LVEF occurs. To
      prevent late tricuspid reoperation, it is important not to leave residual TR of
      grade 2+ or more after tricuspid annuloplasty.

PMID- 11509283
TI  - The double-orifice technique for mitral valve reconstruction: predictors of
      postoperative outcome.
AB  - OBJECTIVE: The 'double-orifice' (DO) technique has been recently proposed as an
      additional option in mitral valve repair (MVR). However, little is known
      regarding the long-term postoperative outcome and the predictors of DO results.
      Therefore, the aim of this study was to evaluate our clinical series and to
      identify prognostic factors of DO repair. METHODS: From 1992, 75 patients
      underwent DO procedure because of severe mitral regurgitation. The study
      population consisted of 48 male and 27 female patients with a mean age of 58+/-13
      years (range 16-80 years). The aetiology of mitral incompetence was Barlow
      disease in 30 cases, rheumatic disease in 18 cases, acute or healed endocarditis
      in 16 cases and other causes in 11 cases. Carpentier rigid ring was used in 38
      patients, whereas autologous pericardium was used in 24 patients. Thirteen
      patients had no annuloplasty procedure. Statistical analysis included univariate
      and multivariate Cox proportional models to evaluate the predictors of the DO
      failure. RESULTS: There were four hospital and three late deaths with a survival
      rate of 92% at 8 years. Mean follow-up was 42+/-24 months (range 1-93 months).
      Twelve patients underwent reoperation (five cases of early failure) and had valve
      replacement, leading to 80% freedom from reoperation at 8 years. At follow-up, 13
      patients had no mitral regurgitation, 36 patients had trivial or mild mitral
      incompetence, whereas eight patients had moderate or severe mitral insufficiency
      at transthoracic echocardiography. Preoperative low left ventricular ejection
      faction, pulmonary arterial hypertension and marked left atrial enlargement were
      predictors (P<0.05) of DO failure at univariate analysis. Pericardial
      annuloplasty was also a risk factor (P<0.05) for unsuccessful DO repair at long
      term. Cox proportional multivariate analysis confirmed left atrial dilatation,
      pulmonary hypertension and pericardial annuloplasty as independent predictors of
      unfavourable postoperative results. CONCLUSIONS: This study suggests that
      preoperative factors, like pulmonary hypertension and severe left atrial
      dilatation, may predict late DO failure. Our findings also indicate that
      pericardial annuloplasty may negatively influence mitral valve reconstruction at
      long term when DO is employed in MVR.

PMID- 11509284
TI  - Pulmonary atresia with ventricular septal defect, extremely hypoplastic pulmonary
      arteries, major aorto-pulmonary collaterals.
AB  - OBJECTIVE: Among 63 patients with pulmonary atresia and ventricular septal defect
      (VSD), 10 patients with extreme hypoplasia of the pulmonary arteries (PA) (mean
      Nakata index 20.6 mm(2)/m(2)), but with confluent arteries and a diminutive main
      PA, and major aorto-pulmonary collaterals (MAPCAS), have been submitted to a
      'rehabilitation' of the PA with several stages: (i) connection between RV and
      PAs, (ii) interventional catheterizations, (iii) complete correction with or
      without unifocalisation. We report here the results of this approach. METHODS:
      The RV-PA connection was direct (nine cases) or with an homograft conduit (one
      case), done under normothermic cardiopulmonary by-pass in patients aged 4.9
      months (range 0.1-18 months). Subsequently, six underwent interventional
      catheterizations (dilations and stents in the PA, MAPCAS occlusion by coils).
      Complete correction was done in seven patients (mean age 30 months, range 8-49).
      One patient is awaiting correction. RESULTS: One patient died after the first
      stage. All patients having had the third stage had a satisfactory development of
      the PA, had a complete closure of the VSD and a satisfactory reconstruction of
      the PA bifurcation. There was one death of severe pulmonary infection 6 months
      after repair. All other patients have been followed by catheterization and/or
      echocardiograms. With a follow-up of 83+/-65 months, all patients are improved,
      50% have no cardiac medications, none has residual shunt, RV/LV pressure ratio is
      0.6 (range 0.3-1). CONCLUSIONS: The strategy of 'rehabilitation' of PA allowing:
      (i) antegrade flow in the PA, (ii) interventional catheterizations, (iii) growth
      of the PA with possible angiogenesis, (iv) complete correction, is a logical
      approach to be undertaken in the young patient and is a valid alternative to
      strategies relying more on MAPCAS for pulmonary vascular supply. The therapeutic
      sequences depend upon the individual anatomy.

PMID- 11509285
TI  - Risk factors influencing early and late mortality after total cavopulmonary
      connection.
AB  - OBJECTIVE: Among the later modifications of the Fontan type procedure, a
      significant alteration was introduced by de Leval and associates when they
      described the total cavopulmonary connection (TCPC). Although current results of
      TCPC have encouraged us to extend this procedure to high risk patients, risk
      factors influencing surgical outcome after TCPC have not been evaluated. We
      review our experiences with TCPC to identify which risk factors may have had a
      considerable impact on the outcome of patients undergoing TCPC and to clarify
      selection criteria of high-risk Fontan candidates for TCPC. PATIENTS AND METHODS:
      We retrospectively reviewed the medical and surgical records of all 76 patients
      who underwent TCPC between July 1988 and August 2000. A cross-sectional review of
      these patients was undertaken. RESULTS: There were eight early deaths and four
      late deaths. In a Fisher's exact test, the following variables were associated
      with an increased early mortality after TCPC: systemic ventricular morphology
      (right ventricle), ejection fraction of the systemic ventricle less than 60%, and
      prolonged cardiopulmonary bypass time (240 min or longer). The log-rank test
      demonstrated that heterotaxy syndrome, moderate to severe atrioventricular valve
      regurgitation, prolonged cardiopulmonary bypass time (240 min or longer), and
      prolonged aortic cross clamp time (70 min or longer) were associated with late
      mortality after TCPC. Six deaths occurred in eight (75%) patients who had six or
      more risk factors, whereas six deaths (9%) occurred in those who had five or
      fewer. CONCLUSIONS: Patients with complex cardiac anomalies who have six or more
      risk factors should be excluded from TCPC candidates.

PMID- 11509286
TI  - Continuous systemic perfusion improves outcome in one stage repair of obstructed
      aortic arch and associated cardiac malformation.
AB  - OBJECTIVE: To determine whether continuous systemic perfusion is of effective use
      when establishing primary repair of the aortic obstruction and associated cardiac
      malformations. METHODS: Since 1991, 56 infants have undergone reconstruction of
      interrupted (in 28) or coarctated (in 28) aorta, concomitantly with closure of
      ventricular septal defects in 37, and repair of other malformations in the
      remaining 19. Of these, total circulatory arrest (30+/-11 min) was employed in
      23. In another 21 patients, perfusion was maintained for the carotid arteries
      with the descending aorta cross-clamped (31+/-15 min). The bodily organs were
      perfused throughout the operative procedures by placing dual aortic cannulae in
      the remaining 12 patients. RESULTS: The postoperative courses were less eventful
      in the non-circulatory arrest group than other groups of patients undergoing
      total or partial circulatory arrest, although these groups were operated in
      different time periods, and consequently, a general progress might be one reason
      for improvements in the surgical outcomes. All patients undergoing no circulatory
      arrest survived the primary repair, could have the sternum primarily closed, and
      had no episodes of cerebral bleeding. Prolonged tracheal intubation was needed
      just in one patient of this group. The amount of urine output during
      cardiopulmonary bypass was significantly greater in the non-circulatory arrest
      group than in the others. The maximal concentrations of urinary beta
      microglobulin, serous creatinine, creatine phosphokinase, and glutamic
      oxaloacetic transaminase were lower in this setting. CONCLUSIONS: Continuous
      systemic perfusion was considered less invasive when concomitantly repairing the
      obstructed aorta and intracardiac malformations.

PMID- 11509287
TI  - Genetic predisposition in patients undergoing cardiopulmonary bypass surgery is
      associated with an increase of inflammatory cytokines.
AB  - OBJECTIVE: Cardiopulmonary bypass (CPB) surgery induces a transient rise in pro
      inflammatory cytokines typically released by activated monocytes. The E4 variant
      of apolipoprotein E is a recognized risk factor for atherosclerosis. It has
      recently been shown that apolipoprotein E affects monocyte functions in vitro and
      leads to higher levels of median lipoprotein (a) in humans. The aim of the study
      is to investigate if the E4 genetic variant of apolipoprotein E affects cytokine
      release after CPB surgery. METHODS: 22 patients were operated on with standard
      coronary artery bypass grafting. Concentrations of interleukin 8 (IL-8) and tumor
      necrosis factor (TNF-alpha) were measured by automated Immulite immunoassay at
      regular intervals within 48 h after surgery. Total apparent cytokine outputs were
      calculated as area under the curve. Results are expressed as mean+/-standard
      deviation and compared by unpaired t-test. RESULTS: In the presented patient
      population 6 (27%) carried the E4 allele. Sixteen (63%) showed no E4 allele. Mean
      cross clamp time (CCT) was 56.2+/-13.5 min versus 55.7+/-12.1 min and CPB time
      was 91.8+/-17.5 versus 93.5+/-15.7 min. No statistical difference between E4
      carriers and E4 non-carriers regarding CCT and CPB was observed. The total amount
      of IL-8 and TNF-alpha was higher in patients carrying the E4 genetic variant of
      apolipoprotein E in comparison to E4 non-carriers (P<0.08, P<0.039). CONCLUSION:
      The presence of the E4 allele is associated with increased release of IL-8 and
      TNF-alpha after CBP surgery. The preoperative determination of E4 in patients
      undergoing cardiac surgery may lead to additional perioperative measures for the
      treatment of an increased systemic inflammatory response.

PMID- 11509288
TI  - Optimization of venous return tubing diameter for cardiopulmonary bypass.
AB  - OBJECTIVE: To determine the optimal venous tubing diameter for adult
      cardiopulmonary bypass (CPB) to improve gravity drainage and to reduce priming
      volume. METHODS: (A) Maximum bovine blood flow rates by gravity drainage were
      assessed in vitro for four different tubing diameters (1/2, 3/8, 5/16,1/4 inch)
      with three different lengths and various pre- and afterloads. Based on the
      results of (A) and multiple regression analyses, we developed equations to
      predict tubing sizes as a function of target flows. (C) The equations obtained in
      (B) were validated by ex vivo bovine experiments. (D) The clinically required
      maximal flows were determined retrospectively by reviewing 119 perfusion records
      at Zurich University. (E) Based on our model (B), the clinical patient and
      hardware requirements, the optimal venous tubing diameter was calculated. (F) The
      optimized venous tubing was evaluated in a prospective clinical trial involving
      312 patients in Hangzhou. RESULTS: For a mean body surface area of 1.83+/-0.2
      m(2), the maximal perfusion flow rate (D) achieved with 1/2-inch (=1.27 cm(2))
      venous tubing was 4.62+/-0.57 l/min (range: 2.50-6.24 l/min). Our validated model
      (B,C) predicted 1.0 cm(2) as optimal cross-sectional area for the venous line.
      New tubing packs developed accordingly were used routinely thereafter. The
      maximal flow rate was 4.93+/-0.58 l/min (range: 3.9-7.0) in patients with a mean
      body surface area of 1.62+/-0.21 m(2). CONCLUSION: The new venous tubing with 1.0
      cm(2) cross-sectional area improves the drainage in the vast majority of adult
      patients undergoing CPB and reduces the priming volume (-27 ml/m). Reduced
      hemodilution can prevent homologous transfusions if a predefined transfusion
      trigger level is not reached.

PMID- 11509289
TI  - Clinical application of vacuum-assisted cardiopulmonary bypass with a pressure
      relief valve.
AB  - OBJECTIVES: Hemodilution induced by cardiopulmonary bypass (CPB) often prevents
      open heart operations without blood transfusion because of a large CPB-priming
      volume. A vacuum-assisted venous drainage system appears to overcome this problem
      and our previous experimental study demonstrated the beneficial effect of a
      vacuum-assisted CPB with a pressure relief valve. In this study, we clinically
      applied this novel system, and evaluated its efficacy by comparing it with the
      results of a conventional siphon-dependent drainage system. METHODS: Sixty
      patients undergoing open heart operation were divided into Group V (vacuum
      assisted system, n=30) and Group S (siphon-dependent system, n=30). The vacuum
      assisted system contains a powerful vacuum generator and a pressure relief valve
      to keep the negative pressure in the reservoir constant when the blood suction is
      used. RESULTS: The CPB-priming volume was significantly smaller in Group V (V vs.
      S: 1071+/-88 vs. 1405+/-137 ml; P<0.01), resulting in the lower hemodilution in
      Group V evidenced by the minimum hemoglobin level (V vs. S: 6.83+/-1.06 vs.
      5.78+/-0.79 mg/dl; P<0.01) and blood transfusion rate (V vs. S: 9 vs. 20%;
      P<0.01). There were no significant differences in the plasma free hemoglobin
      level and the reduction ratio of plasma haptoglobin between the groups.
      CONCLUSIONS: These data demonstrate that this vacuum-assisted CPB can provide
      simplification of the CPB circuit, resulting in a smaller CPB-priming volume and
      lower hemodilution. This vacuum-assisted CPB may attenuate the negative effect of
      CPB by minimizing hemodilution and appears to be a useful modification to
      accomplish no blood-requiring open heart operations.

PMID- 11509290
TI  - Carinal bronchogenic cyst.

PMID- 11509291
TI  - A bronchogenic cyst presenting itself as an aortic arch aneurysm.

PMID- 11509292
TI  - Chronic post-traumatic hernia of the lung.

PMID- 11509293
TI  - True aneurysm of saphenous vein graft.

PMID- 11509294
TI  - Aortic root replacement and coronary interposition using a cryopreserved
      allograft and its branch.
AB  - This communication describes a modified aortic root replacement technique using a
      cryopreserved allograft consisting of the aortic conduit and its branch. This
      method was applied in a patient suffering from infective pseudoaneurysm which had
      developed after aortic root replacement using an artificial graft with a
      mechanical aortic valve. A piece of the innominate artery obtained from the
      aortic allograft was used for interposition between the fragile left coronary
      artery root and the main conduit of the allograft.

PMID- 11509295
TI  - Surgical treatment of a cavernous hemangioma of the left atrial roof.
AB  - A hemangioma that occurs as a primary tumor of the heart is extremely rare. The
      authors experienced a cavernous hemangioma located in the epicardium of the left
      atrial roof in a patient who had paroxysmal atrial fibrillation. Resection of the
      tumor and cryo-coagulation yielded a satisfactory clinical course. No recurrence
      of the tumor is noted at the time of 5 years after operation.

PMID- 11509296
TI  - Vascular complications associated with a large cardiac fibroma.
AB  - A case is reported of a 30-year-old patient with an intrapericardial tumour with
      heart failure. After the diagnostic protocol, surgery was performed initially
      without extra-corporeal circulation (ECC). Due to the location, size and to the
      large connection with the most important vascular structures, the ascending aorta
      ruptured accidentally during resection and was replaced after using ECC in
      emergency. The post-surgical course was regular and the tumour was identified
      histologically as a fibroma.

PMID- 11509297
TI  - Foreign body in tracheal bronchus simulating bronchogenic cancer.
AB  - A foreign body in the bronchial tree may mimic many pathological conditions. We
      present a case of a 62-year-old patient with a foreign body in the tracheal
      bronchus simulating bronchogenic cancer. After the removal of the foreign body,
      there has been a gradual regression of the foreign body induced inflammatory
      changes. To the best of our knowledge, a similar case has not been reported in
      the English medical literature.

PMID- 11509298
TI  - Emergency management of aorto-bronchial fistula after implantation of a self
      expanding bronchial stent.
AB  - We report a case of aorto-bronchial fistula 7 years after implantation of a self
      expanding metal stent into the left main bronchus. The clinical presentation was
      characterised by left-sided chest pain, dyspnea and a single bout of haemoptysis.
      The fistula was surgically managed by aortic resection and primary repair of the
      aorta, and patch repair of the left main bronchus over a Polyflex covered
      bronchial stent. When haemoptysis occurs in a patient with a history of bronchial
      stent implantation, the presence of an aorto-bronchial fistula should be
      considered. Early diagnosis offers the only possibility of recovery through a
      lifesaving surgical procedure.

PMID- 11509299
TI  - Epidural emphysema associated with primary spontaneous pneumothorax.
AB  - A 21-year-old male patient was admitted with spontaneous pneumothorax, and no
      history of asthma. Closed drainage treatment was unsuccessful. Chest computed
      tomography demonstrated pneumomediastinum and subcutaneous emphysema with
      multiple air bubbles within the spinal canal between the levels Th3 and Th11.
      Resection of bullae on the upper lobe and partial pleurectomy were performed.
      Postoperative period was uneventful. Epidural emphysema was resolved
      spontaneously without neurologic symptoms and signs. Intraspinal air, or
      pneumorachis, associated with spontaneous pneumothorax and pneumomediastinum is
      an extremely rare condition. We discussed spontaneous pneumothorax and
      pneumomediastinum as well as epidural pneumatosis and reviewed reported cases in
      the literature.

PMID- 11509300
TI  - Successful removal of a giant recurrent mediastinal liposarcoma involving both
      hemithoraces.
AB  - Primary liposarcomas of the mediastinum are unusual tumors. We report herein a
      case of a 52-year-old woman, who was found to have a mediastinal tumor involving
      both hemithoraces and radiologically showing non-resectable-invasive features to
      the adjacent vital structures. She had a history of left thoracotomy for
      mediastinal schwannoma 14 years previously. The patient underwent an exploratory
      thoracotomy following a preoperative misdiagnosis of an ancient schwannoma.
      Complete removal of the tumor was accomplished through a right posterolateral
      thoracotomy with a subsequent histological diagnosis of a recurrent low-grade
      liposarcoma. A resectable liposarcoma should be considered in the differential
      diagnosis of a mediastinal tumor, although radiologically, the tumor presents
      with invasive features.

PMID- 11509302
TI  - Carotid sinus hypersensitivity in old age: clinical syndrome or physical sign?

PMID- 11509303
TI  - The precision and accuracy of questionnaires for clinical assessment.

PMID- 11509304
TI  - Neuroendocrinology of ageing.
AB  - Many common problems encountered in the ageing patient can be related to
      neuroendocrine phenomena. These include Alzheimer's disease, dementia and
      cognitive dysfunction, depression, Parkinson's disease, hyponatraemia and the
      postmenopausal increase in both vascular risk and osteoporosis. This review
      concentrates on the hypothalamic neuroendocrine system, including the
      dopaminergic, noradrenergic, serotoninergic, cholinergic and neurohypophyseal
      systems and the roles of the anterior pituitary and monoamine oxidases,
      luteinizing hormone-releasing hormone, corticotrophin-releasing factor, the pro
      opiomelanocortin-derived and opioid peptides, peptides involved in growth hormone
      and thyrotropin regulation, and amino acid transmitters.

PMID- 11509305
TI  - Carotid sinus hypersensitivity is common in older patients presenting to an
      accident and emergency department with unexplained falls.
AB  - OBJECTIVE: To determine the prevalence of carotid sinus hypersensitivity and
      orthostatic hypotension in older patients with non-accidental falls attending an
      accident and emergency department. DESIGN: A prospective case-control non
      randomized study. Data were collected from semi-structured interviews, physical
      examination and neurocardiovascular investigations. SETTING: We recruited cases
      and controls from an inner-city accident and emergency department. PARTICIPANTS:
      26 consecutive patients presenting to accident and emergency with non-accidental
      falls and 54 controls matched for age, sex and cognitive function presenting to
      the same department either because of an accidental fall or a reason other than
      falling. MAIN VARIABLES MEASURED: Detailed history and clinical evaluation,
      including postural phasic blood pressure measurements, heart rate and blood
      pressure responses to supine and upright carotid sinus stimulation. RESULTS:
      Orthostatic blood pressure responses did not differ between groups. The heart
      rate and blood pressure responses to carotid sinus massage were abnormal in
      patients with non-accidental falls compared with controls (P=0.002). Asystolic
      responses were present in 12 (46%) of 26 cases and seven (13%) of 54 controls.
      Loss of consciousness occurred during carotid sinus massage in seven (27%) of the
      cases, all of whom had asystole, and in none of the controls. CONCLUSIONS: Almost
      half of the cognitively normal older patients attending accident and emergency
      with non-accidental falls have carotid sinus hypersensitivity, emphasizing that a
      post-fall intervention strategy should include carotid sinus studies.

PMID- 11509306
TI  - The influence of sex and age on response to head-up tilt-table testing in
      patients with recurrent syncope.
AB  - BACKGROUND: Syncope is a common problem, accounting for 6% of hospital
      admissions. Often a diagnosis is not established. Head-up tilt testing is a
      diagnostic test for neuro-cardiogenic syncope, a condition which is often thought
      to affect younger women and be relatively rare in older people. We examined the
      effect of sex and age on response to head-up tilt testing in patients with
      unexplained syncope. METHODS: We performed a retrospective analysis on
      consecutive tilt tests performed using the Westminster drug-free protocol from
      January 1992 to June 1998. Patients were divided into four groups on the basis of
      sex and age (< or = or > 65 years). Responses were classified according to the
      Vasovagal International Study Investigators' criteria. RESULTS: We performed 665
      tests in 590 patients. Mean age was 50 years +/-17.6 (range 12-83). One hundred
      and fifty-three patients (23%) were > 65 years. There was an almost equal sex
      distribution. Two hundred and eight tests (31%) were positive, with 113 (54%)
      showing a mixed response (type 1), 65 (32%) a cardio-inhibitory response (type 2)
      and 30 (14%) a vasodepressor response (type 3). Age and sex had no effect on
      rates of positive tests or time to positive result. There was no gender influence
      with respect to response type. However, subjects aged > 65 years had a higher
      incidence of vasodepressor response (type 3)-29% versus 9% (P < 0.001).
      CONCLUSIONS: Head-up tilt testing is a useful tool in the investigation of all
      patients with suspected neuro-cardiogenic syncope. Age and sex do not influence
      the likelihood of a positive response, but older patients have an increased
      frequency of pure vasodepressor responses. This may have implications with
      respect to treatment strategies.

PMID- 11509307
TI  - Determining minimally important differences for the PDQ-39 Parkinson's disease
      questionnaire.
AB  - OBJECTIVE: To determine minimally important differences for dimensions of the PDQ
      39, a 39-item Parkinson's disease questionnaire. A minimally important difference
      is defined as the smallest change between two scores that is subjectively
      meaningful to patients. Data on minimally important differences are essential for
      the calculation of sample sizes in trials and surveys. METHODS: We conducted a
      postal survey of randomly selected members of 13 local branches of the
      Parkinson's Disease Society, asking them to complete the PDQ-39 on two occasions,
      6 months apart. On the first occasion respondents received the PDQ-39,
      demographic questions and a request to provide their name and address if they
      were willing to take part in the follow-up survey. After 6 months, we sent those
      who had agreed another copy of the questionnaire and also asked them to indicate
      how much change they had experienced since baseline in overall health and in each
      of the eight domains of the questionnaire. RESULTS: We calculated minimally
      important difference for each dimension and the index score for those reporting
      minor change since baseline. The minimally important difference varied across
      dimensions. CONCLUSIONS: These results indicate the minimum magnitude of change
      that should be sought when designing studies to evaluate change over time in
      Parkinson's disease. Since minimally important differences differ across
      dimensions, those designing studies in which sample size calculations are based
      on the PDQ-39 as an outcome measure should select the dimension which is the
      primary variable of interest.

PMID- 11509308
TI  - Stroke rehabilitation after hospital discharge: a randomized trial comparing
      domiciliary and day-hospital care.
AB  - OBJECTIVES: To compare the effectiveness and costs of a new domiciliary
      rehabilitation service for elderly stroke patients with geriatric day-hospital
      care. DESIGN: Randomized controlled trial. PARTICIPANTS: Stroke patients aged 55+
      who required further rehabilitation after hospital discharge or after referral to
      geriatricians from the community. SETTING: Poole area, East Dorset, a mixed
      urban/rural area on the south coast of England. MAIN OUTCOMES: Primary-changes
      between hospital discharge and 6-month follow-up in physical function as measured
      by Barthel index. Secondary-changes over this period in Rivermead Mobility Index
      and mental state (Philadelphia Geriatric Centre Morale Scale) and differences in
      social activity (Frenchay Activities Index) and generic health status (SF-36).
      Health service and social service cost per patient were compared for the two
      groups. RESULTS: 180 patients were eligible and 140 (78%) were randomized. The
      groups were well balanced for age, sex, social class and initial Barthel index.
      We achieved follow-up in 88% of subjects who were alive at 6 months. We detected
      no significant differences in patient outcomes, although there was a non
      significant improvement in measures of physical function and social activity in
      the domiciliary group. Domiciliary patients had more physiotherapy time per
      session and more district nurse time, and made greater use of social service day
      centres and home helps. Total cost per patient did not differ significantly
      between the two groups, with reduced health service costs in the domiciliary arm
      offset by higher social service costs. CONCLUSION: No significant differences
      were detected in the effectiveness of the two services. Neither service
      influenced patients' mental state, and their social activity remained low. Total
      costs were similar. A mixed model of day-hospital and domiciliary care may be
      most cost-effective for community stroke rehabilitation, but this requires
      further evaluation.

PMID- 11509309
TI  - Seasonal cold and circadian changes in blood pressure and physical activity in
      young and elderly people.
AB  - AIM: To test the hypothesis that there is no association between seasonal cold
      and the circadian responses of blood pressure, deep-body temperature and physical
      activity in healthy young and elderly men. METHODS: 25 healthy elderly (aged 70
      82 years) and 21 young volunteers (aged 20-30 years) participated in a 3-year
      prospective cross-seasonal study. RESULTS: Ambulatory day-time blood pressures in
      the older men were higher in the winter than in the summer and higher in both
      seasons than in the young people. The seasonally related differences were
      associated with lower outdoor and indoor temperatures, lower body temperature and
      higher activity levels in the elderly group in the winter. The older but not the
      younger group had higher blood pressure and levels of physical activity at
      certain times of the day in the winter compared with the summer. CONCLUSION: Time
      of-day winter increases in blood pressure in older people may be related to
      increased activity as well as to levels of ambient temperature. Although it is
      generally advantageous for older people to be physically active in order to
      prevent circulatory disease, there may be a rationale for advising that that they
      should avoid intense activity at certain times of the day, especially in the
      winter.

PMID- 11509310
TI  - Dual-task effects of talking while walking on velocity and balance following a
      stroke.
AB  - BACKGROUND: Therapists and nurses often use verbal instruction in the
      rehabilitation of mobility following stroke. This study aimed to determine
      whether performing a verbal cognitive task while walking adversely affected
      patients' balance and velocity. METHODS: There were two counterbalanced
      conditions: walking only and walking and concurrent cognitive activity. The
      cognitive activity used was to give one of two verbal responses to two verbal
      stimuli. An electronic GaitMat measured gait velocity and balance (double support
      time as a percentage of stride time). RESULTS: 11 people with stroke participated
      in the study (five women and six men, mean age 72 years, SD 9). They were on
      average 120 (SD 48) days post-stroke. Velocity decreased (P=0.017) and double
      support time as a percentage of stride time increased (P=0.010) when the
      cognitive activity was added to the test. CONCLUSIONS: Performing a verbal
      cognitive task while walking adversely affected stroke patients' balance and gait
      velocity. Susceptibility to disruption varied within the patient group,
      suggesting clinical heterogeneity. Further research is required before changes to
      clinical practice are justified.

PMID- 11509311
TI  - Relationship between periventricular or deep white matter lesions and arterial
      elasticity indices in very old people.
AB  - OBJECTIVE: To examine the relationship between the presence of cerebral white
      matter lesions and large and small artery elasticity indices in a population of
      healthy, very old subjects. METHODS: We studied 24 subjects (14 women, 10 men)
      with a mean age of 84+/-5 years, who were free from overt neurological,
      cardiovascular or psychiatric illness. We measured blood pressure and heart rate
      in supine and standing positions. Elasticity indices of the large arteries (C1)
      and small arteries (C2) were derived from radial artery pulse waves. Each subject
      had multi-slice spin-echo cerebral magnetic resonance imaging. The severity of
      white matter lesions was graded as 0, 1 or 2. RESULTS: Cerebral white matter
      lesions on magnetic resonance imaging were common in very old apparently healthy
      subjects: grade 0 (n=4, C1=2.68+/-1.80 ml/mmHg and C2=0.045+/-0.017 ml/mmHg),
      grade 1 (n=7, C1=2.13+/-0.36 ml/mmHg and C2=0.040+/-0.016 ml/mmHg) and grade 2
      (n=13, C1=1.12+/-0.36 ml/mmHg and C2=0.018+/-0.003 ml/mmHg). There was no
      significant association between elasticity indices and blood pressure.
      CONCLUSION: In very old, apparently healthy subjects, both large and small artery
      elasticity indices were inversely related to the severity of cerebral white
      matter lesions on magnetic resonance imaging.

PMID- 11509312
TI  - Sex differences of body fat distribution and cardiovascular dysmetabolic factors
      in old age.
AB  - BACKGROUND: The relationship between sexual differences of body fat distribution
      and cardiovascular dysmetabolic factors in old people is controversial.
      OBJECTIVES: To use centrality index-derived body fat distribution to clarify its
      relationship with glucose tolerance status, blood pressure and lipid profile.
      DESIGN: Cross-sectional survey in a tertiary-care medical centre in Tainan,
      Taiwan. SUBJECTS: 114 men and 101 women, aged > or = 60 years. METHODS: We
      measured total % body fat and body fat distribution (reflected as centrality
      index) by dual energy x-ray absorptiometry, and plasma glucose, glycosylated
      haemoglobin, blood pressure, total cholesterol, triglyceride, high-density
      lipoprotein (HDL) cholesterol and atherogenic index (total cholesterol/HDL
      cholesterol). RESULTS: Centrality index showed better linear correlation with
      cardiovascular dysmetabolic factors than body mass index, total % body fat and
      waist-to-hip ratio, except in systolic blood pressure. Women had higher total %
      body fat, but the % abdominal fat and centrality index were both higher in men.
      Subjects with diabetes mellitus had the highest centrality index compared with
      those with impaired or normal glucose tolerance. After adjustment for age and
      total % body fat, men still had higher diastolic blood pressure, triglyceride
      levels and atherogenic indices, but lower HDL cholesterol levels than women.
      However, when further adjusted for centrality index, the sex differences in
      cardiovascular dysmetabolic factors were statistically insignificant.
      CONCLUSIONS: Centrality index is a useful method for assessing body fat
      distribution in older people. Body fat distribution is an important factor in sex
      differences of cardiovascular dysmetabolic factors in old people.

PMID- 11509313
TI  - Using the SF-36 with older adults: a cross-sectional community-based survey.
AB  - OBJECTIVES: To assess the practicality and validity of using the 36-item short
      form health survey (SF-36) in a community-dwelling population over 65, and to
      obtain population scores in this age group. DESIGN: Postal survey, using a
      questionnaire booklet containing the SF-36 and other health-related items, of all
      those aged 65 or over registered with 12 general practices in Sheffield. Non
      respondents received up to two reminders at 3-weekly intervals. SAMPLE: 9897
      subjects, aged 65-104 years. MAIN OUTCOME MEASURES: Scores for the eight
      dimensions of the SF-36 and a modified version of the physical functioning
      dimension. RESULTS: The SF-36 achieved a response rate of 82% (n=8117) and
      dimension completion rates of 86.4-97.7%. Internal consistency measured by
      Cronbach's alpha exceeded 0.80 for all dimensions except social functioning.
      These results compare favourably with postal surveys of younger adults. We
      calculated scores for older adults by age and sex. Comparison with data from
      younger people showed how physical health declines steeply with age, in marked
      contrast to mental health. CONCLUSIONS: The SF-36 is a practical and valid
      instrument for use in postal surveys of older people living at home. The
      population scores provided here may facilitate its use in future surveys of older
      adults.

PMID- 11509314
TI  - Treatment of intractable angina in a nonagenarian patient by direct coronary
      stenting.
AB  - BACKGROUND: A 91-year-old man presented with a 6-month history of exertional
      angina. As he was already on maximally tolerated medical therapy, we decided to
      perform coronary angiography, which revealed severe stenosis of the distal main
      stem coronary artery, OUTCOME: The lesion was crossed with an intra-coronary
      wire, and a stent placed to cover the distal main stem lesion, without prior
      balloon dilatation. The result was satisfactory and he remains symptom-free at 6
      month follow-up. CONCLUSION: Treatment of left main stem lesions with
      percutaneous intervention may be an acceptable alternative to surgery in high
      risk elderly patients. Since percutaneous coronary angioplasty can be performed
      on very elderly patients with a high degree of success, the decision to
      investigate and treat should not be based solely on biological age.

PMID- 11509315
TI  - Lithium-induced nephrogenic diabetes insipidus in older people.
AB  - PRESENTATION: We report two patients. The first is a 68-year-old woman who
      presented with a 2-day history of vomiting. She was hypernatraemic and her
      elevated serum sodium concentration did not improve initially, despite adequate
      fluid replacement. She subsequently developed polyuria and polydipsia. The second
      patient, a 77-year-old woman, presented with delirium and severe hypernatraemia
      after being treated for a chest infection 1 week earlier. Both patients were on
      long-term lithium treatment. INVESTIGATION: In both the cases, a supervised water
      deprivation test done after normalization of the blood biochemistry showed
      partial nephrogenic diabetes insipidus. OUTCOME: Lithium was discontinued.
      CONCLUSION: Older people on lithium-especially those requiring supportive care
      are at risk of severe hypernatraemia after an acute illness or if their fluid
      intake is restricted.

PMID- 11509316
TI  - Ethanol septal ablation for hypertrophic obstructive cardiomyopathy in a very old
      patient.
AB  - BACKGROUND: A 90-year-old woman who had hypertrophic obstructive cardiomyopathy
      presented with drug-refractory heart failure. METHOD: She successfully underwent
      transcoronary ethanol septal ablation under sedation. OUTCOME: There was
      instantaneous improvement in left ventricular outflow tract gradient 6 months
      after discharge, and the symptoms of heart failure have resolved.

PMID- 11509317
TI  - Characteristics of chronic hepatitis C and response to interferon therapy in
      older patients.

PMID- 11509318
TI  - Creutzfeldt-Jakob disease presenting as recurrent falls in an older person.

PMID- 11509319
TI  - Short-term admission of acutely ill older people to nursing homes by general
      practitioners: a national questionnaire survey.

PMID- 11509320
TI  - An uncommon but important cause of severe chest pain in an older population.

PMID- 11509321
TI  - Basic mechanisms of lung development: Eighth Woods Hole Conference on Lung Cell
      Biology 2000.

PMID- 11509322
TI  - Alveolar macrophages and T cells from sarcoid, but not normal lung, are
      permissive to adenovirus infection and allow analysis of NF-kappa b-dependent
      signaling pathways.
AB  - Adenovirus (Adv)-mediated gene transfer requires efficient infection of target
      cells. The objective of this study was to establish whether alveolar macrophages
      (AM) and T cells (AT) from sarcoid patients were permissive to infection with Adv
      vectors and if this property could be used to investigate cytokine gene
      regulation. Sarcoid and normal bronchoalveolar lavage (BAL) specimens infected
      with Adv vectors expressing either beta-galactosidase or a green fluorescent
      protein were analyzed for transgene expression by fluorescence-activated cell
      sorter (FACS) and direct immunofluorescence, respectively. Expression of surface
      antigens previously associated with Adv infection, the coxsackie/adenovirus
      receptor (CAR), alpha v beta 3, and alpha v beta 5 integrins, was also assessed
      using FACS analysis. Sarcoid AM and AT were found to efficiently express Adv
      transgenes, unlike AM from normal volunteers, peripheral blood monocytes, and
      peripheral blood T cells. Cells permissive to Adv infection expressed the CAR and
      alpha v beta 5 integrin (also alpha v beta 3 integrin for AM). The data indicate
      that the upregulation of Adv receptors and the ability to infect sarcoid AM and
      AT are related to the inflammatory environment within the lung. Having
      demonstrated efficient Adv-mediated transgene delivery to sarcoid AM and AT, a
      construct encoding porcine I kappa B alpha was then used to investigate the
      requirement for nuclear factor (NF)-kappa B in the regulation of cytokine gene
      expression in pulmonary sarcoidosis. Overexpression of I kappa B alpha in sarcoid
      BAL specimens indicated that tumor necrosis factor-alpha and interleukin (IL)-6
      production by AM and interferon (IFN)-gamma production by AT is NF-kappa B
      dependent, whereas IL-4 production by AT is NF-kappa B independent. This is the
      first occasion that the requirement for NF-kappa B in IFN-gamma gene expression
      within primary human T cells has been demonstrated. The results of this study
      have implications for the future investigation of molecular pathways in
      inflammatory lung disease.

PMID- 11509323
TI  - Apoptosis in neonatal murine lung exposed to hyperoxia.
AB  - Exposure to high concentrations of oxygen in the neonatal period may impair lung
      growth and is a major contributing factor to the development of bronchopulmonary
      dysplasia. Cell death from hyperoxic injury may occur through either an apoptotic
      or nonapoptotic pathway, and we were interested in determining the type of cell
      death that occurs in the lung of neonatal mice exposed to hyperoxia. We found
      increased levels of Bax messenger RNA, a gene associated with apoptosis, in the
      lungs of neonatal mice born and raised in 92% hyperoxia. We next determined the
      extent of apoptosis taking place in the lungs of neonatal mice exposed to
      hyperoxia using terminal deoxyribonucleotidyl transferase-mediated deoxyuridine
      triphosphate-biotin nick-end labeling in 3.5-, 4.5-, and 5.5-d-old neonatal lung.
      The number of apoptotic cells in peripheral lung was significantly higher in the
      3.5-, 4.5-, and 5.5-d-old mice treated with oxygen compared with that in the room
      air control mice. Further, the number of apoptotic cells in the lung increased
      with longer exposure duration. In murine lung bronchus cells exposed to
      hyperoxia, growth arrest occurred after 48 h of oxygen exposure. Using annexin V
      binding, necrotic cell death was found to be the major form of cell death in
      these cells after 72 h of hyperoxic exposure. We conclude that 92% hyperoxia
      causes significant lung injury in neonatal mice exposed to hyperoxia, and that
      the number of apoptotic cells in the lung increases the longer the duration of
      exposure. The increase in apoptosis from hyperoxic exposure during a critical
      period of lung development may be an important factor in the impaired lung growth
      and remodeling that occur in animals exposed to high oxygen concentrations.
      Finally, it appears that hyperoxic injured cells in neonatal lung undergo both
      apoptotic and nonapoptotic cell death.

PMID- 11509324
TI  - The juxtamembrane lysine and arginine residues of surfactant protein C precursor
      influence palmitoylation via effects on trafficking.
AB  - Surfactant protein (SP)-C propeptide (proSP-C) becomes palmitoylated on cysteines
      5 and 6 before mature SP-C is formed by several proteolytic steps. To study the
      structural requirements for the palmitoylation of proSP-C, his-tagged human proSP
      C (his-proSP-C) and his-proSP-C mutants were expressed in Chinese hamster ovary
      cells and analyzed by metabolic labeling with [(3)H]palmitate and
      immunocytochemistry. Substitution of cysteines 5 and 6 by serines showed that
      these were the only two cysteine residues palmitoylated in his-proSP-C.
      Substitution of the juxtamembrane basic residues lysine and arginine by uncharged
      glutamines led to a large decrease in palmitoylation level of proSP-C. The
      addition of brefeldin A nearly abolished this decrease for the lysine and double
      mutant; the palmitoylation of the arginine mutant increased also, but not to wild
      type (WT) levels. Fluorescence immunocytochemistry showed that WT proSP-C was
      localized in punctate vesicles throughout the cell, whereas the mutant lacking
      the juxtamembrane positive charges was found more perinuclear, probably in the
      endoplasmic reticulum (ER). This indicates that the two basic juxtamembrane
      residues influence palmitoylation of proSP-C by preventing the transport of proSP
      C out of the ER, implying that proSP-C becomes palmitoylated normally in a
      compartment distal to the ER.

PMID- 11509325
TI  - Attenuation of bleomycin-induced pulmonary fibrosis by a catalytic antioxidant
      metalloporphyrin.
AB  - Oxidative stress plays an important role in the development of fibrotic responses
      in the lung. However, it is not clear whether inhibiting oxidative stress with
      antioxidants can attenuate fibrotic processes in the lung. The objective of these
      studies was to test whether the catalytic antioxidant porphyrin manganese (III)
      tetrakis (4-benzoic acid) porphyrin (MnTBAP) could protect mice against bleomycin
      induced lung fibrosis. A 10 mg/kg intraperitoneal dose of MnTBAP was established
      as safe and had a serum and lung half-life of 9.5 h in mice. Based on this data,
      four groups of mice were given one dose of bleomycin (3.2 U/kg, intratracheal) or
      saline and MnTBAP (5 mg/kg, intraperitoneal) or saline twice daily for 14 d. Lung
      fibrosis was assessed by measuring (1) lung hydroxyproline content as an index of
      collagen accumulation, (2) airway dysfunction by whole body plethysmography, and
      (3) histopathology. Bleomycin produced a 20% loss in body weight that was only
      10% in the bleomycin/MnTBAP group. Bleomycin produced a twofold increase in
      hydroxyproline content that was decreased 23% by MnTBAP. Bleomycin produced a
      twofold increase in airway dysfunction that was also attenuated 30% by MnTBAP.
      Histopathologic analysis of the lungs of mice treated with bleomycin demonstrated
      a severe fibrotic response that was attenuated 28% by MnTBAP. Future studies on
      the oxidant mechanisms that MnTBAP is affecting in this bleomycin model of lung
      fibrosis may shed light on potential new therapeutic approaches for treating
      interstitial lung diseases.

PMID- 11509326
TI  - The role of Mac-1 (CD11b/CD18) in antigen-induced airway eosinophilia in mice.
AB  - Mac-1 (CD11b/CD18) is an important adhesion molecule involved in the migration of
      leukocytes, cell signaling, and subsequent secretory responses. Its precise role
      in eosinophil recruitment and activation in vivo is not entirely clear. We wished
      to directly examine the role of Mac-1 in eosinophil migration in a murine model
      of allergic pulmonary inflammation. Briefly, wild-type (C57Bl/6) and Mac-1
      deficient/knockout (Mac-1 KO) mice were intraperitoneally sensitized with
      ovalbumin (OVA) and alum (AlOH) on Days 0 and 14, and intranasally challenged
      with OVA either once on Day 14 or five times on Days 14 and 25 through 28.
      Control animals were challenged with saline. Bronchial hyperresponsiveness was
      measured, bronchoalveolar lavage (BAL) fluid was collected, and lungs were
      harvested for histology 24 h after the last challenge. The data demonstrate that
      wild-type (WT) mice do not respond to one OVA challenge but do develop bronchial
      hyperreactivity and airway and tissue eosinophilia after five OVA challenges.
      Conversely, Mac-1 KO mice develop significant airway eosinophilia after one OVA
      challenge, and the degree of airway inflammation is comparable to that observed
      in allergic WT mice after five challenges. In Mac-1 KO mice, after five
      challenges, bronchial hyperreactivity and airway inflammation was significantly
      enhanced compared with their wild-type counterparts. Administration of an anti
      Mac-1 antibody to WT mice, before each of five intranasal OVA challenges,
      significantly reduces the airway eosinophilia but has no effect on tissue
      eosinophilia or bronchial hyperresponsiveness. Intravenous injection of
      interleukin-5 induced a significant blood eosinophilia in both WT and Mac-1 KO
      mice. Intranasal eotaxin administration induced similar levels of eosinophil
      migration into the lung tissues and airways of both WT and Mac-1 KO mice. In
      conclusion, Mac-1-deficient mice develop enhanced eosinophilic inflammation in
      the lung in response to allergic antigen challenge.

PMID- 11509327
TI  - Activation of nuclear factor-kappa b transcriptional activity in airway
      epithelial cells by thioredoxin but not by N-acetyl-cysteine and glutathione.
AB  - Increasing evidence indicates that intracellular redox status modulates the
      activity of various transcriptional factors, including nuclear factor (NF)-kappa
      B and activator protein-1. Our laboratory has been interested in characterizing
      the role thioredoxin (TRX) plays in regulating cellular redox status in airway
      epithelium. TRX is a small, ubiquitous protein with two redox-active half
      cysteine residues, -Cys-Gly-Pro-Cys, in its active center. Using primary passage
      1 human tracheobronchial epithelial cell cultures and an immortalized human
      bronchial epithelial cell line, HBE1, we observed that tumor necrosis factor
      (TNF)-alpha enhanced NF-kappa B transcriptional activity. This observation was
      based on gel mobility shift assays and interleukin (IL)-8 promoter-reporter gene
      transfection studies. TNF-alpha activation coincided with translocation of NF
      kappa B p65 from the cytoplasm to the nucleus. Pretreatment with N-acetyl
      cysteine (NAC) (1 to 10 mM) or glutathione (1 to 10 mM) inhibited TNF-alpha
      induced activation of NF-kappa B transcriptional activity and IL-8 promoter
      mediated reporter gene expression. In contrast, elevated TRX protein levels in
      cells enhanced TNF-alpha-dependent NF-kappa B transcriptional activity and IL-8
      promoter activity. This observation was independent of the manner in which TRX
      was elevated in cells (e.g., by cotransfection with a FLAG-TRX expression clone,
      or by direct exposure to commercially available human TRX protein). Localization
      of TRX protein by anti-TRX antibody indicated an accumulation of TRX protein in
      the nucleus after TNF-alpha treatment. The nuclear localization phenomenon was
      different from the major cytosolic accumulation of glutathione and NAC. This is
      the first known report demonstrating movement of TRX into the nucleus of airway
      epithelial cells after an inflammatory stress. These results suggest a
      compartment effect of thiol chemicals in the regulation of redox-dependent
      transcriptional activity.

PMID- 11509328
TI  - Small molecular weight secretory factors from Pseudomonas aeruginosa have
      opposite effects on IL-8 and RANTES expression by human airway epithelial cells.
AB  - Pseudomonas aeruginosa is an opportunistic human pathogen that causes both an
      acute lung disease in patients with hospital-acquired pneumonia and a chronic
      lung disease in individuals with cystic fibrosis. Many of the pathophysiologic
      effects of P. aeruginosa infection are due to factors secreted by the bacterium.
      Conditioned media from cultures of P. aeruginosa increased interleukin-8
      expression and decreased regulated on activation, normal T cells expressed and
      secreted (RANTES) expression by human airway epithelial cells. Both of these
      activities were present in heat-treated, protease-treated, small molecular weight
      fractions. The activities were not inhibited by polymyxin B and were not
      extracted into ethyl acetate, suggesting that they were not due to endotoxin or
      autoinducer. Conversely, results from chloroform extractions and studies with a
      phenazine-minus mutant suggested that the blue pigment pyocyanin contributes to
      these activities when present. In addition to the effects of small molecular
      weight factors on cytokine expression, proteases in bacterial-conditioned media
      further decreased levels of RANTES. By altering expression, release, and/or
      activity of inflammatory cytokines, secretory factors from P. aeruginosa could
      disrupt the delicate balance that constitutes the immune response to bacterial
      infection and thus could contribute to the lung damage that occurs in P.
      aeruginosa-infected airways.

PMID- 11509329
TI  - Antibacterial activity of apical surface fluid from the human airway cell line
      Calu-3: pharmacologic alteration by corticosteroids and beta(2)-agonists.
AB  - Calu-3 cells, a human lung carcinoma cell line with properties like serous cells
      of the upper airway, were used to develop an in vitro model for airway
      antibacterial activity. Calu-3 cell monolayers were cultured on permeable
      supports at an air-liquid interface. Apical surface fluid (ASF) was collected by
      washing; antibacterial activity was assayed by incubating ASF washings with
      bacteria for 18 h and counting surviving colony-forming units. ASF washings
      killed Escherichia coli and Pseudomonas aeruginosa. Antibacterial activity was
      salt sensitive and dependent on protein concentration. After washing,
      approximately 30 h were required before antibacterial activity recovered to its
      initial level. After culturing with topical corticosteroids (budesonide,
      triamcinolone, or beclomethasone, 0.1 microg/ml for 48 h), ASF antibacterial
      activity was 4- to 10-fold greater than the ASF from control monolayers. The
      increase in antibacterial activity was dose-dependent. The beta(2)-agonists
      salbutamol and terbutaline (100 microg/ml for 48 h) decreased ASF antibacterial
      activity by 5- to 8-fold. The nonsteroidal anti-inflammatory agents ibuprofen and
      cromolyn sodium had no effect. Our results are most consistent with agonist
      dependent changes in the composition of ASF antibacterial proteins. We conclude
      that Calu-3 cells synthesize and secrete antibacterial proteins and that clinical
      agents can alter these functions.

PMID- 11509330
TI  - Vitronectin and fibronectin function as glucan binding proteins augmenting
      macrophage responses to Pneumocystis carinii.
AB  - beta-glucans represent major structural components of fungal cell walls. We
      recently reported that Pneumocystis carinii beta-glucans stimulate alveolar
      macrophages to release proinflammatory cytokines. Macrophage activation by beta
      glucan is augmented by serum, implying the presence of circulating factors that
      interact with beta-glucans and enhance their ability to stimulate macrophages.
      Using beta-glucan-enriched cell wall fractions from P. carinii and Saccharomyces
      cerevisiae, two prominent proteins were precipitated from serum and demonstrated
      to be vitronectin (VN) and fibronectin (FN) by immune analysis. Preincubation of
      beta-glucan with VN or FN enhanced macrophage activation in response to this cell
      wall component. Because VN and FN accumulate in the lungs during P. carinii
      pneumonia, we further investigated hepatic and pulmonary expression of VN and FN
      messenger RNA during infection. P. carinii pneumonia in rodents is associated
      with increased hepatic expression of VN and FN as well as increased local
      expression of FN in the lung. Because interleukin (IL)-6 represents the major
      regulator of VN and FN expression during inflammatory conditions, we measured
      macrophage IL-6 release in response to stimulation with P. carinii beta-glucan.
      Stimulation of macrophages with P. carinii beta-glucan induced significant
      release of IL-6. Elevated concentrations of IL-6 were noted in the blood of
      infected animals compared with uninfected control animals. These studies indicate
      that VN and FN bind to beta-glucan components of P. carinii and augment
      macrophage inflammatory responses. P. carinii cell wall beta-glucan stimulates
      secretion of IL-6 by macrophages, thereby enhancing hepatic synthesis of both VN
      and FN, and lung synthesis of FN during pneumonia.

PMID- 11509331
TI  - A549 cells can express interleukin-16 and stimulate eosinophil chemotaxis.
AB  - Alveolar epithelial cells produce many types of chemokines such as regulated on
      activation, normal T cells expressed and secreted (RANTES), eotaxin induced by
      interleukin (IL)-1 beta, or tumor necrosis factor (TNF)-alpha and may contribute
      to allergic disease by recruiting eosinophils. However, identification of the
      eosinophil chemotacic activity (ECA) release from A549 cells, an alveolar type II
      cell line, has not yet been completed. Recently, IL-16 was also reported to be a
      potent chemotactic stimulus for CD4(+) T lymphocytes and eosinophils in asthma
      and other pulmonary diseases. To test the possibility that alveolar epithelial
      cells produce IL-16, we analyzed RNA and culture supernatant from A549 cells by
      reverse transcription/ polymerase chain reaction (RT-PCR) and enzyme-linked
      immunosorbent assay (ELISA). The release of ECA from A549 cells was assessed
      using a blind-well chemotactic chamber. IL-16 release was increased in a
      concentration-dependent manner by stimulation with IL-1 beta or TNF-alpha. A549
      cells also expressed IL-16 messenger RNA. The combination of IL-4 and IL-1 beta
      or TNF-alpha had an additive effect on IL-16 production. The release of ECA was
      induced by IL-1 beta or TNF-alpha in a dose-dependent manner. The combination of
      these cytokines had a greater effect than one alone. The blockade of eotaxin and
      IL-16 caused 70% inhibition of ECA, but anti-RANTES antibodies only caused 30%
      inhibition and anti-IL-8 antibodies failed to affect inhibition. These findings
      suggest a role for chemokines released by alveolar epithelial cells in the
      recruitment of eosinophils into the lung in pulmonary disorders such as asthma
      and interstitial lung diseases, and suggested that eotaxin and IL-16 are potent
      and effective eosinophil chemoattractants.

PMID- 11509332
TI  - Urodilatin, a natriuretic peptide stimulating particulate guanylate cyclase, and
      the phosphodiesterase 5 inhibitor dipyridamole attenuate experimental pulmonary
      hypertension: synergism upon coapplication.
AB  - In a model of acute pulmonary hypertension in intact rabbits, we investigated the
      vasodilatory potency of intravascularly administered urodilatin, a renal
      natriuretic peptide type A known to stimulate particulate guanylate cyclase.
      Urodilatin infusion was performed in the absence and presence of the
      phosphodiesterase (PDE) type 5 inhibitor dipyridamole. Stable pulmonary
      hypertension was evoked by continuous infusion of the thromboxane mimetic U46619,
      resulting in approximate doubling of the pulmonary artery pressure (PAP). When
      infused as sole agents, both urodilatin and dipyridamole dose-dependently
      attenuated the pulmonary hypertension, with doses for a 20% decrease in PAP being
      30 ng/kg min for urodilatin and 10 microg/kg min for dipyridamole. A
      corresponding decrease in systemic arterial pressure (SAP) was noted to occur in
      response to both agents. Sequential intravenous administration of a subthreshold
      dose of dipyridamole (1 microg/kg min), which per se did not affect pulmonary and
      systemic hemodynamics, and a standard dose of urodilatin (30 ng/kg min) resulted
      in a significant amplification of both the PAP and the SAP decrease in response
      to the natriuretic peptide. At the same time, manifold enhanced plasmatic cyclic
      guanosine monophosphate (cGMP) levels were detected. Aerosolized dipyridamole
      also dose-dependently attenuated pulmonary hypertension, with only 1 microg/kg
      min being sufficient for a 20% decrease in PAP, with no SAP decline. Preceding
      administration of subthreshold aerosolized dipyridamole (50 ng/kg min) did,
      however, cause only a minor amplification of the pulmonary vasodilatory response
      to a subsequently infused standard dose of urodilatin. In conclusion, this is the
      first study to show that urodilatin does possess vasodilatory potency in the
      pulmonary circulation, and enhanced plasma levels of cGMP and synergy with the
      PDE5 inhibitor dipyridamole both strongly suggest that this effect proceeds via
      guanylate cyclase activation. The effect of infused urodilatin is, however, not
      selective for the pulmonary vasculature, as the systemic vascular resistance
      declines in a corresponding fashion.

PMID- 11509333
TI  - Induction of peroxiredoxin gene expression by oxygen in lungs of newborn
      primates.
AB  - Peroxiredoxin (Prx) is an important antioxidant defense enzyme that reduces
      hydrogen peroxide to molecular oxygen by using reducing equivalents from
      thioredoxin. We report that lung Prx I messenger RNA (mRNA) is specifically
      upregulated by oxygen. Throughout the third trimester, mRNA for Prx I was
      expressed constitutively at low levels in fetal baboon lung. However, after
      premature birth (125 or 140 d gestation), lung Prx I mRNA increased rapidly with
      the onset of oxygen exposure. Premature animals (140 d) breathing 100% O(2)
      developed chronic lung disease within 7 to 14 d. These animals had greater lung
      Prx I mRNA after 1, 6, or 10 d of life than did fetal controls. In 140-d animals
      given lesser O(2) concentrations (as needed) that did not develop chronic lung
      disease, lung Prx I mRNA also was increased on Days 1 and 6, but not Day 10. In
      fetal distal lung explant culture, Prx I mRNA was elevated in 95% O(2), relative
      to 1% oxygen, and remained elevated at 24 h. Prx protein activity increased in
      140-d premature baboons exposed to as-needed oxygen. By contrast, there was a
      decrease in Prx activity in 140-d premature baboons exposed to 100% oxygen. In
      the lung explants from prematures (140 d), there was no significant increase in
      Prx activity in response to 24 h exposure to hyperoxia, whereas exposure of
      explants to 48 h hyperoxia caused a nonsignificant decrease in Prx activity.
      Treatment of lung explants with actinomycin D inhibited Prx mRNA increases in 95%
      oxygen, indicating transcriptional regulation. In cellular signaling studies we
      demonstrated that protein kinase (PK) C activity increased when A549 cells were
      exposed to 95% oxygen, compared with 21% oxygen exposure. In lung explant
      cultures, specific PKC inhibitors calphostin C or GF109203X inhibited the
      increase in Prx I mRNA with 95% oxygen exposure, indicating PKC-mediated
      signaling. The acute increase in gene expression of Prx I in response to oxygen
      suggests an important role for this protein during the transition from relatively
      anaerobic fetal life to oxygen-breathing at birth.

PMID- 11509334
TI  - Interferon-gamma stimulates fractalkine expression in human bronchial epithelial
      cells and regulates mononuclear cell adherence.
AB  - Bronchial epithelial cells may contribute to airway inflammation by releasing
      chemokines and expressing surface membrane molecules involved in the adhesion of
      leukocytes. We found that interferon (IFN)-gamma stimulates expression of
      fractalkine, a potent chemoattractant for monocytes and T lymphocytes, in a time-
      and concentration-dependent manner by normal human bronchial epithelial cells in
      culture. Enhanced expression of fractalkine messenger RNA was confirmed by both
      reverse transcription/polymerase chain reaction and Northern blotting. IFN-gamma
      also stimulated fractalkine protein production and most of the protein was found
      in cell lysates. The adherence of blood mononuclear cells to the monolayers of
      bronchial epithelial cells stimulated with IFN-gamma was partly inhibited by an
      antifractalkine antibody. An antibody against intercellular adhesion molecule-1
      was similarly effective in inhibiting the adhesion. Fractalkine protein levels in
      bronchoalveolar lavage fluids from patients with inflammatory diseases correlated
      positively with mononuclear cell counts in the fluids. The bronchial epithelium
      in a biopsy specimen of lung cancer was stained positively by immunofluorescent
      staining for fractalkine. We conclude that IFN-gamma stimulates fractalkine
      expression by bronchial epithelial cells, which may play an important role in
      inflammatory responses by recruiting mononuclear leukocytes to the bronchial
      epithelium.

PMID- 11509335
TI  - Interleukin-4 rapidly inhibits calcium transients in response to carbachol in
      bovine airway smooth muscle cells.
AB  - To assess interleukin (IL)-4 effects on calcium signaling, bovine airway smooth
      muscle (ASM) cells were loaded with fura-2 and cytosolic calcium ([Ca(2+)](i))
      was measured in single cells by digital microscopy. Human recombinant IL-4 (50
      ng/ml) caused small increases in [Ca(2+)](i). For single cells, carbachol
      stimulated calcium transients were compared before (S1) and after (S2) exposure
      to IL-4 or IL-13. When cells were treated with IL-4 (50 ng/ml) for 20 min, the
      S2/S1 ratio was 0.17 +/- 0.04 (n = 7) even though IL-4 had been washed from the
      chamber for 10 min before the S2 response. In contrast, controls not treated with
      IL-4 had S2/S1 of 0.70 +/- 0.04 (n = 13, P < 0.01). Lower concentrations of IL-4
      variably decreased transients and IL-13 had no effect. In other experiments, 5
      min of IL-4 did not immediately decrease transients but did after a 25-min delay.
      Goat antihuman IL-4 antibody abolished the effect of IL-4. IL-4 (50 ng/ml) also
      inhibited responses to caffeine (S2/S1: 0.30 +/- 0.04 and 0.54 +/- 0.06 for IL-4
      treated versus control). We conclude that IL-4 rapidly inhibited calcium
      transients. Because caffeine-stimulated transients were inhibited, IL-4 may act,
      at least in part, by depleting calcium stores. IL-4 inhibition of cholinergic
      signaling may be important for modulating ASM responses during inflammation.

PMID- 11509337
TI  - GM-CSF increases AP-1 DNA binding and Ref-1 amounts in human alveolar
      macrophages.
AB  - Alveolar macrophages have been implicated in the pathogenesis of a number of
      acute and chronic lung disorders. A characteristic feature of many of the chronic
      lung diseases is that the types of macrophages in the lung change, and in most
      instances, the cells resemble monocyte-like cells. We have previously shown that
      normal human alveolar macrophages have a decreased capacity to express protein
      kinase C (PKC)-induced DNA binding activity of the transcription factor activator
      protein (AP)-1 compared with monocytes. This decrease in AP-1 DNA binding appears
      to be due to a defect in redox regulation of AP-1 proteins via a decrease in the
      redox active protein Ref-1. The hypothesis for this study is that there are
      factors generated during the development of chronic lung disease that increase AP
      1 DNA binding activity and Ref-1 production in human alveolar macrophages. We
      have focused specifically on granulocyte-macrophage colony-stimulating factor (GM
      CSF) as a prototype mediator that can be released by alveolar macrophages and is
      related to the fibrotic process in the lung. We found that after a 24-h
      incubation with GM-CSF, AP-1 DNA binding was significantly increased in both
      unstimulated, interleukin (IL)-13, and phorbol myristate acetate (PMA)-stimulated
      alveolar macrophages and that there was a corresponding increase in Ref-1 protein
      by Western blot analysis in the PMA-stimulated group. This suggests that disease
      related cytokines such as GM-CSF and IL-13 may modulate AP-1 DNA binding activity
      in alveolar macrophages.

PMID- 11509336
TI  - Cytokine inhibition of fibroblast-induced gel contraction is mediated by PGE(2)
      and NO acting through separate parallel pathways.
AB  - Contraction of three-dimensional collagen gels is a model of the contraction that
      characterizes normal healing and remodeling after injury. In the current study,
      we evaluated the hypothesis that a number of inflammatory factors, including
      tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, and interferon (IFN)
      gamma, modulate this process by induction of prostaglandin (PG) E(2) and nitric
      oxide (NO) production and that these secondary mediators function in an autocrine
      or paracrine manner to modulate contraction. Human fetal lung fibroblasts (HFL)
      were cultured in type I collagen gels and floated in medium containing TNF-alpha,
      IL-1 beta, or IFN-gamma alone or in combination (cytomix). All cytokines
      inhibited the contraction significantly. The potency order was IL-1 beta, TNF
      alpha, IFN-gamma. The cytomix was no more potent than was IL-1 beta alone. PGE(2)
      production was increased by TNF-alpha (5.0 versus 0.16 ng/ml, P < 0.01), IL-1
      beta (5.3 versus 0.16 ng/ml, P < 0.01), and cytomix (5.9 versus 0.16 ng/ml, P <
      0.01), and was completely inhibited by indomethacin. Indomethacin (P < 0.05) and
      L-NG-monomethyl arginine citrate (L-NMMA) (P < 0.05) alone both partially
      attenuated the inhibition of contraction caused by cytokines alone or by cytomix.
      Indomethacin and L-NMMA together attenuated inhibition more than either alone (P
      < 0.05). Exogenous PGE(2) and exogenous NO donors (DETA nononate and 5-amino-3-(4
      morpholinyl)-1,2,3-oxadiazolium chloride) inhibited the contraction
      significantly. The protein kinase A inhibitor KT5270 and the protein kinase G
      inhibitor Rp-pCPT-cGMPS attenuated the inhibition induced by PGE(2) and NO,
      respectively. In summary, PGE(2) and NO appear to function in parallel as
      autocrine/paracrine mediators of cytokine-driven fibroblast inhibition of the
      contraction of collagen gels and may contribute to remodeling during repair and
      inflammation in lung disorders.

PMID- 11509338
TI  - Photoreduction and reoxidation of the three iron-sulfur clusters of reaction
      centers of green sulfur bacteria.
AB  - Iron-sulfur clusters are the terminal electron acceptors of the photosynthetic
      reaction centers of green sulfur bacteria and photosystem I. We have studied
      electron-transfer reactions involving these clusters in the green sulfur
      bacterium Chlorobium tepidum, using flash-absorption spectroscopic measurements.
      We show for the first time that three different clusters, named F(X), F(1), and
      F(2), can be photoreduced at room temperature during a series of consecutive
      flashes. The rates of electron escape to exogenous acceptors depend strongly upon
      the number of reduced clusters. When two or three clusters are reduced, the
      escape is biphasic, with the fastest phase being 12-14-fold faster than the
      slowest phase, which is similar to that observed after single reduction. This is
      explained by assuming that escape involves mostly the second reducible cluster.
      Evidence is thus provided for a functional asymmetry between the two terminal
      acceptors F(1) and F(2). From multiple-flash experiments, it was possible to
      derive the intrinsic recombination rates between P840(+) and reduced iron-sulfur
      clusters: values of 7, 14, and 59 s(-1) were found after one, two and three
      electron reduction of the clusters, respectively. The implications of our results
      for the relative redox potentials of the three clusters are discussed.

PMID- 11509339
TI  - Viscoelastic dynamics of actin filaments coupled to rotary F-ATPase: angular
      torque profile of the enzyme.
AB  - ATP synthase (F(O)F(1)) operates as two rotary motor/generators coupled by a
      common shaft. Both portions, F(1) and F(O), are rotary steppers. Their symmetries
      are mismatched (C(3) versus C(10-14)). We used the curvature of fluorescent actin
      filaments, attached to the rotating c-ring, as a spring balance (flexural
      rigidity of 8. 10(-26) Nm(2)) to gauge the angular profile of the output torque
      at F(O) during ATP hydrolysis by F(1) (see theoretical companion article (.
      Biophys. J. 81:1234-1244.)). The large average output torque (50 +/- 6 pN. nm)
      proved the absence of any slip. Variations of the torque were small, and the
      output free energy of the loaded enzyme decayed almost linearly over the angular
      reaction coordinate. Considering the threefold stepping and high activation
      barrier of the driving motor proper, the rather constant output torque implied a
      soft elastic power transmission between F(1) and F(O). It is considered as
      essential, not only for the robust operation of this ubiquitous enzyme under
      symmetry mismatch, but also for a high turnover rate of the two counteracting and
      stepping motor/generators.

PMID- 11509340
TI  - Viscoelastic dynamics of actin filaments coupled to rotary F-ATPase: curvature as
      an indicator of the torque.
AB  - ATP synthase (F-ATPase) operates as an electrochemical-to-mechanical-to-chemical
      energy transducer with an astounding 360 degrees rotary motion of subunits
      epsilongammac(10-14) (rotor) against delta(alphabeta)(3)ab(2) (stator). The
      enzyme's torque as a function of the angular reaction coordinate in relation to
      ATP-synthesis/hydrolysis, internal elasticity, and external load has remained an
      important issue. Fluorescent actin filaments of micrometer length have been used
      to detect the rotation as driven by ATP hydrolysis. We evaluated the viscoelastic
      dynamics of actin filaments under the influence of enzyme-generated torque,
      stochastic Langevin force, and viscous drag. Modeling with realistic parameters
      revealed the dominance of the lowest normal mode. Because of its slow relaxation
      (approximately 100 ms), power strokes of the enzyme were expected to appear
      strongly damped in recordings of the angular velocity of the filament. This
      article describes the theoretical background for the alternative use of the
      filament as a spring balance. The enzyme's angular torque profile under load can
      be gauged by measuring the average curvature and the stochastic fluctuations of
      actin filaments. Pertinent experiments were analyzed in the companion paper.

PMID- 11509341
TI  - Noncontact dipole effects on channel permeation. IV. Kinetic model of 5F-Trp(13)
      gramicidin A currents.
AB  - Nonlinear least squares fitting was used to assign rate constants for the three
      barrier, two-site, double-occupancy, single-filing kinetic model for previously
      reported current-voltage relations of (5F-Indole)Trp(13) gramicidin A and
      gramicidin A channels (, 75:2830-2844). By judicious coupling of parameters, it
      was possible to reduce the parameter space from 64 parameters to 24, and a
      reasonable fit consistent with other experimental data was obtained. The main
      features of the fit were that fluorination increased the rate constant for
      translocation by a factor of 2.33, consistent with a free energy change in the
      translocation barrier of -0.50 kcal/mol, and increased first-ion binding affinity
      by a factor of 1.13, primarily by decreasing the first-ion exit rate constant.
      The translocation rate constant was 5.62 times slower in diphytanoyl
      phosphatidylcholine (DPhPC) bilayers than in monoolein (GMO) bilayers (coupled
      for the four combinations of peptide and salt), suggesting a 44.2-mV difference
      in the projection of the interfacial dipole into the channel. Thus fluorination
      caused increased currents in DPhPC bilayers, where a high interfacial dipole
      potential makes translocation more rate limiting because the translocation
      barrier was reduced, and decreased currents in GMO bilayers, where ion exit or
      entry is rate limiting because these barriers were increased.

PMID- 11509343
TI  - Application of the stretched exponential function to fluorescence lifetime
      imaging.
AB  - Conventional analyses of fluorescence lifetime measurements resolve the
      fluorescence decay profile in terms of discrete exponential components with
      distinct lifetimes. In complex, heterogeneous biological samples such as tissue,
      multi-exponential decay functions can appear to provide a better fit to
      fluorescence decay data than the assumption of a mono-exponential decay, but the
      assumption of multiple discrete components is essentially arbitrary and is often
      erroneous. Moreover, interactions, both between fluorophores and with their
      environment, can result in complex fluorescence decay profiles that represent a
      continuous distribution of lifetimes. Such continuous distributions have been
      reported for tryptophan, which is one of the main fluorophores in tissue. This
      situation is better represented by the stretched-exponential function (StrEF). In
      this work, we have applied, for the first time to our knowledge, the StrEF to
      time-domain whole-field fluorescence lifetime imaging (FLIM), yielding both
      excellent tissue contrast and goodness of fit using data from rat tissue. We note
      that for many biological samples for which there is no a priori knowledge of
      multiple discrete exponential fluorescence decay profiles, the StrEF is likely to
      provide a truer representation of the underlying fluorescence dynamics.
      Furthermore, fitting to a StrEF significantly decreases the required processing
      time, compared with a multi-exponential component fit and typically provides
      improved contrast and signal/noise in the resulting FLIM images. In addition, the
      stretched-exponential decay model can provide a direct measure of the
      heterogeneity of the sample, and the resulting heterogeneity map can reveal
      subtle tissue differences that other models fail to show.

PMID- 11509342
TI  - Noncontact dipole effects on channel permeation. V. Computed potentials for
      fluorinated gramicidin.
AB  - Experimental and theoretical calculations indicate that the dipole moment of the
      four Trp side chains in gramicidin A (gA) channels modify channel conductance
      through long-range electrostatic interactions. Electrostatic ion/side-chain
      interaction energies along the channel were computed with CHARMM using ab initio
      atom charges for native and 4-, 5-, or 6-fluorinated Trp side chains. The bulk
      water reaction to the polar side chains was included using the method of images
      as implemented by, and channel waters in idealized structures were included.
      Ion/Trp interaction energies were approximately -0.6 kcal/mol throughout the
      channel for all four of the native Trp pairs. Channel waters produced a modest
      reduction in the magnitude of interactions, essentially offsetting images
      representing the bulk water outside the channel. The effects of side-chain
      fluorination depended on ring position and, to a lesser extent, residue number.
      Compared with native Trp, 5-fluorination reduces the translocation barrier with
      minor effects on the exit barrier. In contrast, 6-fluorination primarily reduces
      exit barrier. 4-Fluorination produces a more complex double-well energy profile.
      Effects of measured side-chain movements resulting from fluorination or change in
      lipid bilayer were negligible whereas thermal side chain librations cause large
      effects, especially in the region of the ion-binding sites.

PMID- 11509344
TI  - Evaluation of site-directed spin labeling for characterizing protein-ligand
      complexes using simulated restraints.
AB  - Simulation studies have been performed to evaluate the utility of site-directed
      spin labeling for determining the structures of protein-ligand complexes, given a
      known protein structure. Two protein-ligand complexes were used as model systems
      for these studies: a 1.9-A-resolution x-ray structure of a dihydrofolate
      reductase mutant complexed with methotrexate, and a 1.5-A-resolution x-ray
      structure of the V-Src tyrosine kinase SH2 domain complexed with a five-residue
      phosphopeptide. Nitroxide spin labels were modeled at five dihydrofolate
      reductase residue positions and at four SH2 domain residue positions. For both
      systems, after energy minimization, conformational ensembles of the spin-labeled
      residues were generated by simulated annealing while holding the remainder of the
      protein-ligand complex fixed. Effective distances, simulating those that could be
      obtained from (1)H-NMR relaxation measurements, were calculated between ligand
      protons and the spin labels. These were converted to restraints with several
      different levels of precision. Restrained simulated annealing calculations were
      then performed with the aim of reproducing target ligand-binding modes. The
      effects of incorporating a few supplementary short-range (< or =5.0 A) distance
      restraints were also examined. For the dihydrofolate reductase-methotrexate
      complex, the ligand-binding mode was reproduced reasonably well using relatively
      tight spin-label restraints, but methotrexate was poorly localized using loose
      spin-label restraints. Short-range and spin-label restraints proved to be
      complementary. For the SH2 domain-phosphopeptide complex without the short-range
      restraints, the peptide did not localize to the correct depth in the binding
      groove; nevertheless, the orientation and internal conformation of the peptide
      was reproduced moderately well. Use of the spin-label restraints in conjunction
      with the short-range restraints resulted in relatively well defined structural
      ensembles. These results indicate that restraints derived from site-directed spin
      labeling can contribute significantly to defining the orientations and
      conformations of bound ligands. Accurate ligand localization appears to require
      either a few supplementary short-range distance restraints, or relatively tight
      spin-label restraints, with at least one spin label positioned so that some of
      the restraints draw the ligand into the binding pocket in the latter case.

PMID- 11509345
TI  - Fluctuations and the Hofmeister effect.
AB  - The Hofmeister effect consists in changes of protein solubility triggered by
      neutral electrolyte cosolutes. Based on the assumption that salts cause
      stochastic fluctuations of the free energy barrier profiles, a kinetic theory of
      this phenomenon is proposed. An exponentially correlated noise, of amplitude
      proportional to the salt concentration, is added to each energy level, and the
      time-dependence of the mean protein concentration is calculated. It is found that
      the theory yields the well-known Setschenow equation if the noise correlation
      time is low in comparison to the aggregation time constant. Experimental data on
      salting-in agents are well fitted, whereas, in the case of salting-out cosolutes,
      two independent dichotomic fluctuations are needed to fit the data. This may
      result from the fact that, in both cases, the low-concentration regime is
      dominated by salting-in electrostatic contributions, whereas, at high salt
      concentrations, electron donor/acceptor interactions become important; these have
      opposite effects. The theory offers a novel way to metricate Hofmeister effects
      and also leads to thermodynamic quantities, which account for the influence of
      salts. The formalism may also be applied to describe kinetic phenomena in the
      presence of cosolutes.

PMID- 11509346
TI  - Molecular dynamics force probe simulations of antibody/antigen unbinding:
      entropic control and nonadditivity of unbinding forces.
AB  - Unbinding of a spin-labeled dinitrophenyl (DNP) hapten from the monoclonal
      antibody AN02 F(ab) fragment has been studied by force probe molecular dynamics
      (FPMD) simulations. In our nanosecond simulations, unbinding was enforced by
      pulling the hapten molecule out of the binding pocket. Detailed inspection of the
      FPMD trajectories revealed a large heterogeneity of enforced unbinding pathways
      and a correspondingly large flexibility of the binding pocket region, which
      exhibited induced fit motions. Principal component analyses were used to estimate
      the resulting entropic contribution of approximately 6 kcal/mol to the AN02/DNP
      hapten bond. This large contribution may explain the surprisingly large effect on
      binding kinetics found for mutation sites that are not directly involved in
      binding. We propose that such "entropic control" optimizes the binding kinetics
      of antibodies. Additional FPMD simulations of two point mutants in the light
      chain, Y33F and I96K, provided further support for a large flexibility of the
      binding pocket. Unbinding forces were found to be unchanged for these two
      mutants. Structural analysis of the FPMD simulations suggests that, in contrast
      to free energies of unbinding, the effect of mutations on unbinding forces is
      generally nonadditive.

PMID- 11509347
TI  - A diffusion-translocation model for gradient sensing by chemotactic cells.
AB  - Small chemotactic cells like Dictyostelium and neutrophils transduce shallow
      spatial chemoattractant gradients into strongly localized intracellular
      responses. We show that the capacity of a second messenger to establish and
      maintain localized signals, is mainly determined by its dispersion range, lambda
      = the square root of D(m)/k(-1), which must be small compared to the cell's
      length. Therefore, short-living second messengers (high k(-1)) with diffusion
      coefficients D(m) in the range of 0-5 microm(2) s(-1) are most suitable.
      Additional to short dispersion ranges, gradient sensing may include positive
      feedback mechanisms that lead to local activation and global inhibition of second
      messenger production. To introduce the essential nonlinear amplification, we have
      investigated models in which one or more components of the signal transduction
      cascade translocate from the cytosol to the second messenger in the plasma
      membrane. A one-component model is able to amplify a 1.5-fold difference of
      receptor activity over the cell length into a 15-fold difference of second
      messenger concentration. Amplification can be improved considerably by
      introducing an additional activating component that translocates to the membrane.
      In both models, communication between the front and the back of the cell is
      mediated by partial depletion of cytosolic components, which leads to both local
      activation and global inhibition. The results suggest that a biochemically simple
      and general mechanism may explain various signal localization phenomena not only
      in chemotactic cells but also those occurring in morphogenesis and cell
      differentiation.

PMID- 11509348
TI  - Force-induced denaturation of RNA.
AB  - We quantitatively describe an RNA molecule under the influence of an external
      force exerted at its two ends as in a typical single-molecule experiment. Our
      calculation incorporates the interactions between nucleotides by using the
      experimentally determined free energy rules for RNA secondary structure and
      models the polymeric properties of the exterior single-stranded regions
      explicitly as elastic freely jointed chains. We find that despite complicated
      secondary structures, force-extension curves are typically smooth in quasi
      equilibrium. We identify and characterize two sequence/structure-dependent
      mechanisms that, in addition to the sequence-independent entropic elasticity of
      the exterior single-stranded regions, are responsible for the smoothness. These
      involve compensation between different structural elements on which the external
      force acts simultaneously and contribution of suboptimal structures,
      respectively. We estimate how many features a force-extension curve recorded in
      nonequilibrium, where the pulling proceeds faster than rearrangements in the
      secondary structure of the molecule, could show in principle. Our software is
      available to the public through an "RNA-pulling server."

PMID- 11509349
TI  - Protein-protein ratchets: stochastic simulation and application to processive
      enzymes.
AB  - Interaction between a protein and a series of binding sites on a cytoskeletal
      substrate can create a resistance, or "protein friction," as the protein is moved
      along the substrate. If attachment and detachment rates are specified
      asymmetrically, this resistance can depend on the direction of movement, and the
      binding interaction acts as a ratchet. Stochastic computer simulations have been
      used to examine this type of protein-protein interaction. The performance of a
      protein-protein ratchet in the piconewton and nanometer range is significantly
      limited by thermal fluctuations, which in experimental measurements with single
      molecules are evident as Brownian motion. Simulations with a two-component model
      combining a conventional motor enzyme model with a protein-protein ratchet
      confirm previous suggestions that the processive movement of a single motor
      enzyme molecule against a load, as seen in experiments with inner arm dynein
      molecules, might be made possible by an accessory protein interaction that
      prevents backward slippage. When this accessory protein interaction is defined so
      that it acts as a ratchet, backward slippage can be prevented with minimal
      interference with forward progression.

PMID- 11509350
TI  - Molecular dynamics simulations of wild-type and mutant forms of the Mycobacterium
      tuberculosis MscL channel.
AB  - The crystal structure of the Mycobacterium tuberculosis homolog of the bacterial
      mechanosensitive channel of large conductance (Tb-MscL) provides a unique
      opportunity to consider mechanosensitive signal transduction at the atomic level.
      Molecular dynamics simulations of the Tb-MscL channel embedded in an explicit
      lipid bilayer and of its C-terminal helical bundle alone in aqueous solvent were
      performed. C-terminal calculations imply that although the helix bundle structure
      is relatively unstable at physiological pH, it may have been stabilized under low
      pH conditions such as those used in the crystallization of the channel. Specific
      mutations to the C-terminal region, which cause a similar conservation of the
      crystal structure conformation, have also been identified. Full channel
      simulations were performed for the wild-type channel and two experimentally
      characterized gain-of-function mutants, V21A and Q51E. The wild-type Tb-MscL
      trajectory gives insight into regions of relative structural stability and
      instability in the channel structure. Channel mutations led to observable changes
      in the trajectories, such as an alteration of intersubunit interactions in the
      Q51E mutant. In addition, interesting patterns of protein-lipid interactions,
      such as hydrogen bonding, arose in the simulations. These and other observations
      from the simulations are relevant to previous and ongoing experimental studies
      focusing on characterization of the channel.

PMID- 11509351
TI  - Stochastic simulation of hemagglutinin-mediated fusion pore formation.
AB  - Studies on fusion between cell pairs have provided evidence that opening and
      subsequent dilation of a fusion pore are stochastic events. Therefore, adequate
      modeling of fusion pore formation requires a stochastic approach. Here we present
      stochastic simulations of hemagglutinin (HA)-mediated fusion pore formation
      between HA-expressing cells and erythrocytes based on numerical solutions of a
      master equation. The following elementary processes are taken into account: 1)
      lateral diffusion of HA-trimers and receptors, 2) aggregation of HA-trimers to
      immobilized clusters, 3) reversible formation of HA-receptor contacts, and 4)
      irreversible conversion of HA-receptor contacts into stable links between HA and
      the target membrane. The contact sites between fusing cells are modeled as
      superimposed square lattices. The model simulates well the statistical
      distribution of time delays measured for the various intermediates of fusion pore
      formation between cell-cell fusion complexes. In particular, these are the
      formation of small ion-permissive and subsequent lipid-permissive fusion pores
      detected experimentally (R. Blumenthal, D. P. Sarkar, S. Durell, D. E. Howard,
      and S. J., J. Cell Biol. 135:63-71). Moreover, by averaging the simulated
      individual stochastic time courses across a larger population of cell-cell
      complexes the model also provides a reasonable description of kinetic
      measurements on lipid mixing in cell suspensions (T. Danieli, S. L. Pelletier,
      Y.I. Henis, and J. M. White, 1996, J. Cell Biol. 133:559-569).

PMID- 11509352
TI  - Carbohydrate-protein recognition: molecular dynamics simulations and free energy
      analysis of oligosaccharide binding to concanavalin A.
AB  - Carbohydrate ligands are important mediators of biomolecular recognition.
      Microcalorimetry has found the complex-type N-linked glycan core pentasaccharide
      beta-GlcNAc-(1-->2)-alpha-Man-(1-->3)-[beta-GlcNAc-(1-->2)-alpha-Man-(1-->6)]-Man
      to bind to the lectin, Concanavalin A, with almost the same affinity as the
      trimannoside, Man-alpha-(1-->6)-[Man-alpha-(1-->3)]-Man. Recent determination of
      the structure of the pentasaccharide complex found a glycosidic linkage psi
      torsion angle to be distorted by 50 degrees from the NMR solution value and
      perturbation of some key mannose-protein interactions observed in the structures
      of the mono- and trimannoside complexes. To unravel the free energy contributions
      to binding and to determine the structural basis for this degeneracy, we present
      the results of a series of nanosecond molecular dynamics simulations, coupled to
      analysis via the recently developed MM-GB/SA approach (Srinivasan et al., J. Am.
      Chem. Soc. 1998, 120:9401-9409). These calculations indicate that the strength of
      key mannose-protein interactions at the monosaccharide site is preserved in both
      the oligosaccharides. Although distortion of the pentasaccharide is significant,
      the principal factor in reduced binding is incomplete offset of ligand and
      protein desolvation due to poorly matched polar interactions. This analysis
      implies that, although Concanavalin A tolerates the additional 6 arm GlcNAc
      present in the pentasaccharide, it does not serve as a key recognition
      determinant.

PMID- 11509353
TI  - Intercellular ice propagation: experimental evidence for ice growth through
      membrane pores.
AB  - Propagation of intracellular ice between cells significantly increases the
      prevalence of intracellular ice in confluent monolayers and tissues. It has been
      proposed that gap junctions facilitate ice propagation between cells. This study
      develops an equation for capillary freezing-point depression to determine the
      effect of temperature on the equilibrium radius of an ice crystal sufficiently
      small to grow through gap junctions. Convection cryomicroscopy and video image
      analysis were used to examine the incidence and pattern of intracellular ice
      formation (IIF) in the confluent monolayers of cell lines that do (MDCK) and do
      not (V-79W) form gap junctions. The effect of gap junctions on intracellular ice
      propagation was strongly temperature-dependent. For cells with gap junctions, IIF
      occurred in a directed wave-like pattern in 100% of the cells below -3 degrees C.
      At temperatures above -3 degrees C, there was a marked drop in the incidence of
      IIF, with isolated individual cells initially freezing randomly throughout the
      sample. This random pattern of IIF was also observed in the V-79W monolayers and
      in MDCK monolayers treated to prevent gap junction formation. The significant
      change in the low temperature behavior of confluent MDCK monolayers at -3 degrees
      C is likely the result of the inhibition of gap junction-facilitated ice
      propagation, and supports the theory that gap junctions facilitate ice nucleation
      between cells.

PMID- 11509354
TI  - Stimulus-dependent control of inositol 1,4,5-trisphosphate-induced Ca(2+)
      oscillation frequency by the endoplasmic reticulum Ca(2+)-ATPase.
AB  - In many cell types, receptor stimulation evokes cytosolic calcium oscillations
      with a frequency that depends on agonist dose. Previous studies demonstrated
      controversial effects of changing the activity of the endoplasmic reticulum
      Ca(2+)-ATPase upon the frequency of oscillations. By numerical simulations, we
      found that the model of De Young and Keizer (J. Keizer and G.W. De Young, 1994,
      J. Theor. Biol. 166: 431-442), unlike other models, can explain the observed
      discrepancies, assuming that the different experiments were performed at
      different stimulus levels. According to model predictions, partial inhibition of
      internal calcium pumps is expected to increase frequency at low stimulus strength
      and should have an opposite effect at strong stimuli. Similar results were
      obtained using an analytical estimation of oscillation period, based on calcium
      dependent channel activation and inactivation. In experiments on HeLa cells, 4 nM
      thapsigargin increased the frequency of calcium oscillations induced by 1 and 2.5
      microM histamine but had no effect on supramaximally stimulated cells. In HEp-2
      cells, 2 nM thapsigargin slowed down the rapid, ATP-induced oscillations. Our
      results suggest that in the investigated cell types, the De Young-Keizer model
      based on inositol 1,4,5-trisphosphate-dependent calcium-induced calcium release
      can properly describe intracellular calcium oscillations.

PMID- 11509355
TI  - Heterotypic docking of Cx43 and Cx45 connexons blocks fast voltage gating of
      Cx43.
AB  - Immunohistochemical co-localization of distinct connexins (Cxs) in junctional
      areas suggests the formation of heteromultimeric channels. To determine the
      docking effects of the heterotypic combination of Cx43 and Cx45 on the voltage
      gating properties of their channels, we transfected DNA encoding Cx43 or Cx45
      into N2A neuroblastoma or HeLa cells. Using a double whole-cell voltage-clamp
      technique, we determined macroscopic and single-channel gating properties of the
      intercellular channels formed. Cx43-Cx45 heterotypic channels had rectifying
      properties where Cx45 connexons inactivated rapidly upon hyperpolarizing voltage
      pulses applied to the Cx45-expressing cell. During depolarizing pulses to the
      Cx45-expressing cell, Cx43 connexons inactivated with substantially reduced
      kinetics as compared with homotypic Cx43 channels. Similar slow kinetics was
      observed for homotypic Cx43M257 (truncation mutant). Heterotypic channels had a
      main conductance whose value was predicted by the sum of corresponding homomeric
      connexon conductances; it was not voltage dependent and had no detectable
      residual conductance. The voltage-gating kinetics of heterotypic channels and
      their single-channel behavior implicate a role for the Cx43 carboxyl-terminal
      domain in the fast gating mechanism and in the establishment of residual
      conductance. Our results also suggest that heterotypic docking may lead to
      conformational changes that inhibit this action of the Cx43 carboxyl-terminal
      domain.

PMID- 11509356
TI  - Two domains in dihydropyridine receptor activate the skeletal muscle Ca(2+)
      release channel.
AB  - The II-III cytoplasmic loop of the skeletal muscle dihydropyridine receptor
      (DHPR) alpha(1)-subunit is essential for skeletal-type excitation-contraction
      coupling. Single channel and [(3)H]ryanodine binding studies with a full-length
      recombinant peptide (p(666-791)) confirmed that this region specifically
      activates skeletal muscle Ca2+ release channels (CRCs). However, attempts to
      identify shorter domains of the II-III loop specific for skeletal CRC activation
      have yielded contradictory results. We assessed the specificity of the
      interaction of five truncated II-III loop peptides by comparing their effects on
      skeletal and cardiac CRCs in lipid bilayer experiments; p(671-680) and p(720-765)
      specifically activated the submaximally Ca2+-activated skeletal CRC in
      experiments using both mono and divalent ions as current carriers. A third
      peptide, p(671-690), showed a bimodal activation/inactivation behavior indicating
      a high-affinity activating and low-affinity inactivating binding site. Two other
      peptides (p(681-690) and p(681-685)) that contained an RKRRK-motif and have
      previously been suggested in in vitro studies to be important for skeletal-type E
      C coupling, failed to specifically stimulate skeletal CRCs. Noteworthy, p(671
      690), p(681-690), and p(681-685) induced similar subconductances and long-lasting
      channel closings in skeletal and cardiac CRCs, indicating that these peptides
      interact in an isoform-independent manner with the CRCs.

PMID- 11509357
TI  - Modulation of proton transfer in the water wire of dioxolane-linked gramicidin
      channels by lipid membranes.
AB  - Proton conductance (g(H)) in single SS stereoisomers of dioxolane-linked
      gramicidin A (gA) channels were measured in different phospholipid bilayers at
      different HCl concentrations. In particular, measurements were obtained in
      bilayers made of 1,2-diphytanoyl 3-phosphocholine (DiPhPC) or its ethylated
      derivative 1,2-diphytanoyl 3-ethyl-phosphocholine (et-DiPhPC,). The difference
      between these phospholipids is that in et-DiPhPC one of the phosphate oxygens is
      covalently linked to an ethyl group and cannot be protonated. In relatively
      dilute acid solutions, g(H) in DiPhPC is significantly higher than in et-DiPhPC.
      At high acid concentrations, g(H) is the same in both diphytanoyl bilayers. Such
      differences in g(H) can be accounted for by surface charge effects at the
      membrane/solution interfaces. In the linear portion of the log g(H)-log [H]
      relationship, g(H) values in diphytanoyl bilayers were significantly larger
      (approximately 10-fold) than in neutral glyceryl monooleate (GMO) membranes. The
      slopes of the linear log-log relationships between g(H) and [H] in diphytanoyl
      and GMO bilayers are essentially the same (approximately 0.76). This slope is
      significantly lower than the slope of the log-log plot of proton conductivity
      versus proton concentration in aqueous solutions (approximately 1.00). Because
      the chemical composition of the membrane-channel/solution interface is strikingly
      different in GMO and diphytanoyl bilayers, the reduced slope in g(H)-[HCl]
      relationships may be a characteristic of proton transfer in the water wire inside
      the SS channel. Values of g(H) in diphytanoyl bilayers were also significantly
      larger than in membranes made of the more common biological phospholipids 1
      palmitoyl 2-oleoyl phosphocholine (POPC) or 1-palmitoyl 2-oleoyl
      phosphoethanolamine (POPE). These differences, however, cannot be accounted for
      by different surface charge effects or by different internal dipole potentials.
      On the other hand, maximum g(H) measured in the SS channel does not depend on the
      composition of the bilayer and is determined essentially by the reduced mobility
      of protons in concentrated acid solutions. Finally, no experimental evidence was
      found in support of a lateral proton movement at the phospholipid/solution
      interface contributing to g(H) in single SS channels. Protein-lipid interactions
      are likely to modulate g(H) in the SS channel.

PMID- 11509358
TI  - Evidence for two concentration-dependent processes for beta-subunit effects on
      alpha1B calcium channels.
AB  - beta-Subunits of voltage-dependent Ca(2+) channels regulate both their expression
      and biophysical properties. We have injected a range of concentrations of beta3
      cDNA into Xenopus oocytes, with a fixed concentration of alpha1B (Ca(V)2.2) cDNA,
      and have quantified the corresponding linear increase of beta3 protein. The
      concentration dependence of a number of beta3-dependent processes has been
      studied. First, the dependence of the a1B maximum conductance on beta3-protein
      occurs with a midpoint around the endogenous concentration of beta3
      (approximately 17 nM). This may represent the interaction of the beta-subunit,
      responsible for trafficking, with the I-II linker of the nascent channel. Second,
      the effect of beta3-subunits on the voltage dependence of steady-state
      inactivation provides evidence for two channel populations, interpreted as
      representing alpha1B without or with a beta3-subunit, bound with a lower affinity
      of 120 nM. Third, the effect of beta3 on the facilitation rate of G-protein
      modulated alpha1B currents during a depolarizing prepulse to +100 mV provides
      evidence for the same two populations, with the rapid facilitation rate being
      attributed to Gbetagamma dissociation from the beta-subunit-bound alpha1B
      channels. The data are discussed in terms of two hypotheses, either binding of
      two beta-subunits to the alpha1B channel or a state-dependent alteration in
      affinity of the channel for the beta-subunit.

PMID- 11509359
TI  - Elastic thickness compressibilty of the red cell membrane.
AB  - We have used an ultrasensitive force probe and optical interferometry to examine
      the thickness compressibility of the red cell membrane in situ. Pushed into the
      centers of washed-white red cell ghosts lying on a coverglass, the height of the
      microsphere-probe tip relative to its closest approach on the adjacent glass
      surface revealed the apparent material thickness, which began at approximately 90
      nm per membrane upon detection of contact (force approximately 1-2 pN). With
      further impingement, the apparent thickness per membrane diminished over a soft
      compliant regime that spanned approximately 40 nm and stiffened on approach to
      approximately 50 nm under forces of approximately 100 pN. The same force
      thickness response was obtained on recompression after retraction of the probe,
      which demonstrated elastic recoverability. Scaled by circumferences of the
      microspheres, the forces yielded energies of compression per area which exhibited
      an inverse distance dependence resembling that expected for flexible polymers.
      Attributed to the spectrin component of the membrane cytoskeleton, the energy
      density only reached one thermal energy unit (k(B)T) per spectrin tetramer near
      maximum compression. Hence, we hypothesized that the soft compliant regime probed
      in the experiments represented the compressibility of the outer region of
      spectrin loops and that the stiff regime < 50 nm was the response of a compact
      mesh of spectrin backed by a hardcore structure. To evaluate this hypothesis, we
      used a random flight theory for the entropic elasticity of polymer loops to model
      the spectrin network. We also examined the possibility that additional steric
      repulsion and apparent thickening could arise from membrane thermal-bending
      excitations. Fixing the energy scale to k(B)T/spectrin tetramer, the combined
      elastic response of a network of ideal polymer loops plus the membrane steric
      interaction correlated well with the measured dependence of energy density on
      distance for a statistical segment length of approximately 5 nm for spectrin
      (i.e., free chain end-to-end length of approximately 29 nm) and a hardcore limit
      of approximately 30 nm for underlying structure.

PMID- 11509360
TI  - Reconstitution of membrane proteins into giant unilamellar vesicles via peptide
      induced fusion.
AB  - In this work, we present a protocol to reconstitute membrane proteins into giant
      unilamellar vesicles (GUV) via peptide-induced fusion. In principle, GUV provide
      a well-defined lipid matrix, resembling a close-to-native state for biophysical
      studies, including optical microspectroscopy, of transmembrane proteins at the
      molecular level. Furthermore, reconstitution in this manner would also eliminate
      potential artifacts arising from secondary interactions of proteins, when
      reconstituted in planar membranes supported on solid surfaces. However, assembly
      procedures of GUV preclude direct reconstitution. Here, for the first time, a
      method is described that allows the controlled incorporation of membrane proteins
      into GUV. We demonstrate that large unilamellar vesicles (LUV, diameter 0.1
      microm), to which the small fusogenic peptide WAE has been covalently attached,
      readily fuse with GUV, as revealed by monitoring lipid and contents mixing by
      fluorescence microscopy. To monitor contents mixing, a new fluorescence-based
      enzymatic assay was devised. Fusion does not introduce changes in the membrane
      morphology, as shown by fluorescence correlation spectroscopy. Analysis of
      fluorescence confocal imaging intensity revealed that approximately 6 to 10 LUV
      fused per microm(2) of GUV surface. As a model protein, bacteriorhodopsin (BR)
      was reconstituted into GUV, using LUV into which BR was incorporated via
      detergent dialysis. BR did not affect GUV-LUV fusion and the protein was stably
      inserted into the GUV and functionally active. Fluorescence correlation
      spectroscopy experiments show that BR inserted into GUV undergoes unrestricted
      Brownian motion with a diffusion coefficient of 1.2 microm(2)/s. The current
      procedure offers new opportunities to address issues related to membrane-protein
      structure and dynamics in a close-to-native state.

PMID- 11509361
TI  - Barrel-stave model or toroidal model? A case study on melittin pores.
AB  - Transmembrane pores induced by amphiphilic peptides, including melittin, are
      often modeled with the barrel-stave model after the alamethicin pore. We examine
      this assumption on melittin by using two methods, oriented circular dichroism
      (OCD) for detecting the orientation of melittin helix and neutron scattering for
      detecting transmembrane pores. OCD spectra of melittin were systematically
      measured. Melittin can orient either perpendicularly or parallel to a lipid
      bilayer, depending on the physical condition and the composition of the bilayer.
      Transmembrane pores were detected when the helices oriented perpendicularly to
      the plane of the bilayers, not when the helices oriented parallel to the
      bilayers. The evidence that led to the barrel-stave model for alamethicin and
      that to the toroidal model for magainin were reviewed. The properties of melittin
      pores are closely similar to that of magainin but unlike that of alamethicin. We
      conclude that, among naturally produced peptides that we have investigated, only
      alamethicin conforms to the barrel-stave model. Other peptides, including
      magainins, melittin and protegrins, all appear to induce transmembrane pores that
      conform to the toroidal model in which the lipid monolayer bends continuously
      through the pore so that the water core is lined by both the peptides and the
      lipid headgroups.

PMID- 11509363
TI  - Characteristics of pyrene phospholipid/gamma-cyclodextrin complex.
AB  - Recently, it was demonstrated that gamma-cyclodextrins (gamma-CDs) greatly
      accelerates transfer of hydrophobic pyrene-labeled and other fluorescent
      phospholipid derivatives from vesicles to cells in culture (). To understand
      better the characteristics of this process, we studied the interaction of gamma
      CD with pyrene-labeled phosphatidylcholines (PyrPCs) using a variety of physical
      methods. Either one or both of the acyl chains of PC was labeled with a pyrene
      moiety (monoPyrPCs and diPyrPCs, respectively), and the length of the labeled
      chain(s) varied from 4 to 14 carbons. Fluorescent binding assays showed that the
      association constant decreases strongly with increasing acyl chain length.
      PyrPC/gamma-CD stoichiometry was 1:2 for the shorter chain species, but changed
      to 1:3 when the acyl chain length exceeded 8 (diPyrPCs) or 10 (monoPyrPCs)
      carbons. The activation energy for the formation of diPyr(10)PC/gamma-CD complex
      was high, i.e., +92 kJ/mol, indicating that the phospholipid molecule has to
      fully emerge from the bilayer before complex formation can take place. The free
      energy, enthalpy, and entropy of transfer of monoPyrPC from bilayer to gamma-CD
      complex were close to zero. The absorption, Fourier transform infrared, and
      fluorescence spectral measurements and lifetime analysis indicated that the
      pyrene moiety lies inside the CD cavity and is conformationally restricted,
      particularly when the labeled chain is short. The acyl chains of a PyrPC molecule
      seem to share a CD cavity rather than occupy different ones. The present data
      provide strong evidence that the ability of gamma-CD to enhance intermembrane
      transfer of pyrene-labeled phospholipids is based on the formation of
      stoichiometric complexes in the aqueous phase. This information should help in
      designing CD derivatives that are more efficient lipid carriers then those
      available at present.

PMID- 11509362
TI  - Characterization of cholesterol-sphingomyelin domains and their dynamics in
      bilayer membranes.
AB  - Lipids segregate with each other into small domains in biological membranes,
      which can facilitate the associations of particular proteins. The segregation of
      cholesterol and sphingomyelin (SPM) into domains known as rafts is thought to be
      especially important. The formation of rafts was studied by using planar bilayer
      membranes that contained rhodamine-phosphatidylethanolamine (rho-DOPE) as a
      fluorescent probe, and wide-field fluorescence microscopy was used to detect
      phase separation of the probe. A fluorescently labeled GM(1), known to
      preferentially partition into rafts, verified that rho-DOPE faithfully reported
      the rafts. SPM-cholesterol domains did not form at high temperatures but
      spontaneously formed when temperature was lowered to below the melting
      temperature of the SPM. Saturated acyl chains on SPMs therefore promote the
      formation of rafts. The domains were circular (resolution > or = 0.5 microm),
      quickly reassumed their circular shape after they were deformed, and merged with
      each other to create larger domains, all phenomena consistent with liquid-ordered
      (l(o)) rather than solid-ordered (s(o)) domains. A saturated phosphatidylcholine
      (PC), disteoryl-PC, could substitute for SPM to complex with cholesterol into a
      l(o)-domain. But in the presence of cholesterol, a saturated
      phosphatidylethanolamine or phosphatidylserine yielded s(o)-domains of irregular
      shape. Lipids with saturated acyl chains can therefore pack well among each other
      and with cholesterol to form l(o)-domains, but domain formation is dependent on
      the polar headgroup of the lipid. An individual raft always extended through both
      monolayers. Degrading cholesterol in one monolayer with cholesterol oxidase first
      caused the boundary of the raft to become irregular; then the raft gradually
      disappeared. The fluid nature of rafts, demonstrated in this study, may be
      important for permitting dynamic interactions between proteins localized within
      rafts.

PMID- 11509364
TI  - A new high-temperature transition of crystalline cholesterol in mixtures with
      phosphatidylserine.
AB  - Phosphatidylserine and cholesterol are two major components of the cytoplasmic
      leaflet of the plasma membrane. The arrangement of cholesterol is markedly
      affected by the presence of phosphatidylserine in model membranes. At relatively
      low mol fractions of cholesterol in phosphatidylserine, compared with other
      phospholipids, cholesterol crystallites are formed that exhibit both thermotropic
      phase transitions as well as diffraction of x-rays. In the present study we have
      observed and characterized a novel thermotropic transition occurring in mixtures
      of phosphatidylserine and cholesterol. This new transition is observed at 96
      degrees C by differential scanning calorimetry (DSC), using a heating scan rate
      of 2 degrees C/min. Observation of the transition requires that the hydrated
      lipid mixture be incubated for several days, depending on the temperature of
      incubation. The rate of formation of the material exhibiting a transition at 96
      degrees C is more rapid at higher incubation temperatures. At 37 degrees C the
      half-time of conversion is approximately 7 days. Concomitant with the appearance
      of the 96 degrees C peak the previously known transitions of cholesterol,
      occurring at approximately 38 degrees C and 75 degrees C on heating scans of
      freshly prepared suspensions, disappear. These two transitions correspond to the
      polymorphic transition of anhydrous cholesterol and to the dehydration of
      cholesterol monohydrate, respectively. The loss of the 75 degrees C peak takes a
      longer time than that of the 38 degrees C peak, indicating that anhydrous
      cholesterol first gets hydrated to the monohydrate form exhibiting a transition
      at 75 degrees C and subsequently is converted by additional time of incubation to
      an altered form of the monohydrate, showing a phase transition at 96 degrees C.
      After several weeks of incubation at 37 degrees C, only the form with a phase
      transition at 96 degrees C remains. If such a sample undergoes several successive
      heating and cooling cycles, the 96 degrees C peak disappears and the 38 degrees C
      transition reappears on heating. For samples of 1-palmitoyl-2-oleoyl
      phosphatidylserine or of 1-stearoyl-2-oleoyl phosphatidylserine having mol
      fractions of cholesterol between 0.4 and 0.7, the 38 degrees C transition that
      reappears after the melting of the 96 degrees C component generally has the same
      enthalpy as do freshly prepared samples. This demonstrates that, at least for
      these samples, the amount of anhydrous cholesterol crystallites formed is indeed
      a property of the lipid mixture. We have also examined variations in the method
      of preparation of the sample and find similar behavior in all cases, although
      there are quantitative differences. The 96 degrees C transition is partially
      reversible on cooling and reheating. This transition is also scan rate dependent,
      indicating that it is, at least in part, kinetically determined. The enthalpy of
      the 96 degrees C transition, after incubation of the sample for 3 weeks at 37
      degrees C is dependent on the ratio of cholesterol to 1-palmitoyl-2-oleoyl
      phosphatidylserine or to 1-stearoyl-2-oleoyl phosphatidylserine, with the
      enthalpy per mole cholesterol increasing between cholesterol mol fractions of 0.2
      and 0.5. Dimyristoyl phosphatidylserine at a 1:1 molar ratio with cholesterol,
      after incubation at 37 degrees C, exhibits a transition at 95 degrees C that
      reverses on cooling at 44 degrees C, instead of 60 degrees C, as observed with
      either 1-palmitoyl-2-oleoyl phosphatidylserine or 1-stearoyl-2-oleoyl
      phosphatidylserine. These findings along with the essential absence of the 96
      degrees C transition in pure cholesterol or in cholesterol/phosphatidylcholine
      mixtures, indicates that the phospholipid affects the characteristics of the
      transition, and therefore the cholesterol crystallites must be in direct contact
      with the phospholipid and are not simply in the form of pure crystals of
      cholesterol. These observations are particularly important in view of recent
      observations of the presence of cholesterol crystals in biological systems.

PMID- 11509365
TI  - Comprehensive kinetic analysis of influenza hemagglutinin-mediated membrane
      fusion: role of sialate binding.
AB  - The data of Danieli et al. (J. Cell Biol. 133:559-569, 1996) and Blumenthal et
      al. (J. Cell Biol. 135:63-71, 1996) for fusion between hemagglutinin (HA)
      expressing cells and fluorescently labeled erythrocytes has been analyzed using a
      recently published comprehensive mass action kinetic model for HA-mediated
      fusion. This model includes the measurable steps in the fusion process, i.e.,
      first pore formation, lipid mixing, and content mixing of aqueous fluorescent
      markers. It contains two core parameters of the fusion site architecture. The
      first is the minimum number of aggregated HAs needed to sustain subsequent fusion
      intermediates. The second is the minimal number of those HAs within the fusogenic
      aggregate that must undergo a slow "essential" conformational change needed to
      initiate bilayer destabilization. Because the kinetic model has several
      parameters, each data set was exhaustively fitted to obtain all best fits.
      Although each of the data sets required particular parameter ranges for best
      fits, a consensus subset of these parameter ranges could fit all of the data.
      Thus, this comprehensive model subsumes the available mass action kinetic data
      for the fusion of HA-expressing cells with erythrocytes, despite the differences
      in assays and experimental design, which necessitated transforming fluorescence
      dequenching intensities to equivalent cumulative waiting time distributions. We
      find that HAs bound to sialates on glycophorin can participate in fusion as
      members of the fusogenic aggregate, but they cannot undergo the essential
      conformational change that initiates bilayer destabilization, thus solving a long
      standing debate. Also, the similarity in rate constants for lipid mixing and
      content mixing found here for HA-mediated fusion and by Lee and Lentz (Proc.
      Natl. Acad. Sci. U.S.A. 95:9274-9279, 1998) for PEG-induced fusion of
      phosphatidylcholine liposomes supports the idea that subsequent to stable fusion
      pore formation, the evolution of fusion intermediates is determined more by the
      lipids than by the proteins.

PMID- 11509366
TI  - Thermodynamic effects of the hydrophobic surfactant proteins on the early
      adsorption of pulmonary surfactant.
AB  - We determined the influence of the two hydrophobic proteins, SP-B and SP-C, on
      the thermodynamic barriers that limit adsorption of pulmonary surfactant to the
      air-water interface. We compared the temperature and concentration dependence of
      adsorption, measured by monitoring surface tension, between calf lung surfactant
      extract (CLSE) and the complete set of neutral and phospholipids (N&PL) without
      the proteins. Three stages generally characterized the various adsorption
      isotherms: an initial delay during which surface tension remained constant, a
      fall in surface tension at decreasing rates, and, for experiments that reached
      approximately 40 mN/m, a late acceleration of the fall in surface tension to
      approximately 25 mN/m. For the initial change in surface tension, the surfactant
      proteins accelerated adsorption for CLSE relative to N&PL by more than ten-fold,
      reducing the Gibbs free energy of transition (DeltaG(O)) from 119 to 112 kJ/mole.
      For the lipids alone in N&PL, the enthalpy of transition (DeltaH(O), 54 kJ/mole)
      and entropy (-T. DeltaS, 65 kJ/mole at 37 degrees C) made roughly equal
      contributions to DeltaG(O). The proteins in CLSE had little effect on -T.
      DeltaS(O) (68 kJ/mole), but lowered DeltaG(O) for CLSE by reducing DeltaH(O) (44
      kJ/mole). Models of the detailed mechanisms by which the proteins facilitate
      adsorption must meet these thermodynamic constraints.

PMID- 11509367
TI  - Detergent-like action of the antibiotic peptide surfactin on lipid membranes.
AB  - Surfactin is a bacterial lipopeptide with powerful surfactant-like properties.
      High-sensitivity isothermal titration calorimetry was used to study the self
      association and membrane partitioning of surfactin. The critical micellar
      concentration (CMC), was 7.5 microM, the heat of micellization was endothermic
      with DeltaH(w-->m)(Su) = +4.0 kcal/mol, and the free energy of micellization
      DeltaG(O,w-->m)(Su) = -9.3 kcal/mol (25 degrees C; 100 mM NaCl; 10 mM TRIS, 1 mM
      EDTA; pH 8.5). The specific heat capacity of micellization was deduced from
      temperature dependence of DeltaH(w-->m)(Su) as DeltaC(w-->m)(P) = -250 +/- 10
      cal/(mol.K). The data can be explained by combining the hydrophobicity of the
      fatty acyl chain with that of the hydrophobic amino acids. The membrane partition
      equilibrium was studied using small (30 nm) and large (100 nm) unilamellar POPC
      vesicles. At 25 degrees C, the partition coefficient, K, was (2.2 +/- 0.2) x
      10(4) M(-1) for large vesicles leading to a free energy of DeltaG(O, w-->b)(Su) =
      -8.3 kcal/mol. The partition enthalpy was again endothermic, with DeltaH(w-
      >b)(Su) = 9 +/- 1 kcal/mol. The strong preference of surfactin for micelle
      formation over membrane insertion explains the high membrane-destabilizing
      activity of the peptide. For surfactin and a variety of non-ionic detergents, the
      surfactant-to-lipid ratio, inducing membrane solubilization, R(sat)(b), can be
      predicted by the simple relationship R(sat)(b) approximately K. CMC.

PMID- 11509368
TI  - Controlling the direction of kinesin-driven microtubule movements along
      microlithographic tracks.
AB  - Motor proteins are able to move protein filaments in vitro. However, useful work
      cannot be extracted from the existing in vitro systems because filament motions
      are in random directions on two-dimensional surfaces. We succeeded in restricting
      kinesin-driven movements of microtubules along linear tracks by using micrometer
      scaled grooves lithographically fabricated on glass surfaces. We also
      accomplished the extraction of unidirectional movement from the bidirectional
      movements along the linear tracks by adding arrowhead patterns on the tracks.
      These "rectifiers" enabled us to construct microminiturized circulators in which
      populations of microtubules rotated in one direction, and to actively transport
      microtubules between two pools connected by arrowheaded tracks in the fields of
      micrometer scales.

PMID- 11509369
TI  - Fluorescent coumarin-labeled nucleotides to measure ADP release from actomyosin.
AB  - Several coumarin-labeled nucleotides have been synthesized, based on 2'(3')-O-(2
      aminoethyl)carbamoyl-ATP (edaATP). The fluorescent coumarins coupled with the
      free amino group are 7-diethylaminocoumarin-3-carboxylic acid (to give deac
      edaATP), coumarin 343 (but-edaATP) and 7-ethylamino-8-bromocoumarin-3-carboxylic
      acid (mbc-edaATP). The carbamoyl linkage of these nucleotide analogs undergoes
      interconversion between 2'- and 3'-hydroxyl attachment very slowly, so that the
      2'- and 3'-isomers were separated and stored with minimal equilibration. 3'-Deac
      edaADP had fluorescence excitation and emission maxima at 430 nm and 477 nm, with
      a fluorescence quantum yield of 0.012. The equivalent data for 3'-but-edaADP are
      445 nm, 494 nm, and 0.51, respectively, and for 3'-mbc-edaADP, 405 nm, 464 nm,
      and 0.62. The interaction with skeletal myosin subfragment 1 was measured in the
      absence and presence of actin. In each case the fluorescence was decreased when
      bound to subfragment 1, 3-fold for 3'-deac-edaADP, 7-fold for 3'-but-edaADP, and
      11-fold for 3'-mbc-edaADP. Steady-state ATPase measurements and the kinetics of
      binding and release of nucleotides were similar to those reported for the natural
      nucleotide. Large fluorescence changes could be observed for the release of these
      analogs from actomyosin subfragment 1, enabling a direct measurement of the
      kinetics of this process. In the case of 3'-deac-edaADP a rate constant of 474 s(
      1) was measured (at pH 7.0, 20 degrees C, and low ionic strength).

PMID- 11509370
TI  - Stability and folding rates of domains spanning the large A-band super-repeat of
      titin.
AB  - Titin is a very large (>3 MDa) protein found in striated muscle where it is
      believed to participate in myogenesis and passive tension. A prominent feature in
      the A-band portion of titin is the presence of an 11-domain super-repeat of
      immunoglobulin superfamily and fibronectin-type-III-like domains. Seven
      overlapping constructs from human cardiac titin, each consisting of two or three
      domains and together spanning the entire 11-domain super-repeat, have been
      expressed in Escherichia coli. Fluorescence unfolding experiments and circular
      dichroism spectroscopy have been used to measure folding stabilities for each of
      the constructs and to assign unfolding rates for each super-repeat domain.
      Immunoglobulin superfamily domains were found to fold correctly only in the
      presence of their C-terminal fibronectin type II domain, suggesting close and
      possibly rigid association between these units. The domain stabilities, which
      range from 8.6 to 42 kJ mol(-1) under physiological conditions, correlate with
      previously reported mechanical forces required to unfold titin domains.
      Individual domains vary greatly in their rates of unfolding, with a range of
      unfolding rate constants between 2.6 x 10(-6) and 1.2 s(-1). This variation in
      folding behavior is likely to be an important determinant in ensuring independent
      folding of domains in multi-domain proteins such as titin.

PMID- 11509371
TI  - Silver(I) complexes with DNA and RNA studied by Fourier transform infrared
      spectroscopy and capillary electrophoresis.
AB  - Ag(I) is a strong nucleic acids binder and forms several complexes with DNA such
      as types I, II, and III. However, the details of the binding mode of silver(I) in
      the Ag-polynucleotides remains unknown. Therefore, it was of interest to examine
      the binding of Ag(I) with calf-thymus DNA and bakers yeast RNA in aqueous
      solutions at pH 7.1-6.6 with constant concentration of DNA or RNA and various
      concentrations of Ag(I). Fourier transform infrared spectroscopy and capillary
      electrophoresis were used to analyze the Ag(I) binding mode, the binding
      constant, and the polynucleotides' structural changes in the Ag-DNA and Ag-RNA
      complexes. The spectroscopic results showed that in the type I complex formed
      with DNA, Ag(I) binds to guanine N7 at low cation concentration (r = 1/80) and
      adenine N7 site at higher concentrations (r = 1/20 to 1/10), but not to the
      backbone phosphate group. At r = 1/2, type II complexes formed with DNA in which
      Ag(I) binds to the G-C and A-T base pairs. On the other hand, Ag(I) binds to the
      guanine N7 atom but not to the adenine and the backbone phosphate group in the Ag
      RNA complexes. Although a minor alteration of the sugar-phosphate geometry was
      observed, DNA remained in the B-family structure, whereas RNA retained its A
      conformation. Scatchard analysis following capillary electrophoresis showed two
      binding sites for the Ag-DNA complexes with K(1) = 8.3 x 10(4) M(-1) for the
      guanine and K(2) = 1.5 x 10(4) M(-1) for the adenine bases. On the other hand, Ag
      RNA adducts showed one binding site with K = 1.5 x 10(5) M(-1) for the guanine
      bases.

PMID- 11509372
TI  - Significance of ligand tails for interaction with the minor groove of B-DNA.
AB  - Minor groove binding ligands are of great interest due to their extraordinary
      importance as transcription controlling drugs. We performed three molecular
      dynamics simulations of the unbound d(CGCGAATTCGCG)(2) dodecamer and its
      complexes with Hoechst33258 and Netropsin. The structural behavior of the
      piperazine tail of Hoechst33258, which has already been shown to be a contributor
      in sequence-specific recognition, was analyzed. The simulations also reveal that
      the tails of the ligands are able to influence the width of the minor groove. The
      groove width is even sensitive for conformational transitions of these tails,
      indicating a high adaptability of the minor groove. Furthermore, the ligands also
      exert an influence on the B(I)/B(II) backbone conformational substate behavior.
      All together these results are important for the understanding of the binding
      process of sequence-specific ligands.

PMID- 11509373
TI  - Temperature and halide dependence of the photocycle of halorhodopsin from
      Natronobacterium pharaonis.
AB  - The photocycle kinetics of halorhodopsin from Natronobacterium pharaonis
      (pHR(575)) was analyzed at different temperatures and chloride concentrations as
      well as various halides. Over the whole range of modified parameters the kinetics
      can be adequately modeled with six apparent rate constants. Assuming a model in
      which the observed rates are assigned to irreversible transitions of a single
      relaxation chain, six kinetically distinguishable states (P(1-6)) are discernible
      that are formed from four chromophore states (spectral archetypes S(j): K(570),
      L(N)(520), O(600), pHR'(575)). Whereas P(1) coincides with K(570) (S(1)), both
      P(2) and P(3) have identical spectra resembling L(520) (S(2)), thus representing
      a true spectral silent transition between them. P(4) constitutes a fast
      temperature-dependent equilibrium between the chromophore states S(2) and S(3)
      (L(520) and O(600), respectively). The subsequent equilibrium (P(5)) of the same
      spectral archetypes is only moderately temperature dependent but shows
      sensitivity toward the type of anion and the chloride concentration. Therefore,
      S(2) and S(3) occurring in P(4) as well as in P(5) have to be distinguished and
      are assigned to L(520)<--> O(1)(600) and O(2)(600)<--> N(520) equilibrium,
      respectively. It is proposed that P(4) and P(5) represent the anion release and
      uptake steps. Based on the experimental data affinities of the halide binding
      sites are estimated.

PMID- 11509374
TI  - Self diffusion and spectral modifications of a membrane protein, the Rubrivivax
      gelatinosus LH2 complex, incorporated into a monoolein cubic phase.
AB  - The light-harvesting complex LH2 from a purple bacterium, Rubrivivax gelatinosus,
      has been incorporated into the Q230 cubic phase of monoolein. We measured the
      self-diffusion of LH2 in detergent solution and in the cubic phase by
      fluorescence recovery after photobleaching. We investigated also the absorption
      and fluorescence properties of this oligomeric membrane protein in the cubic
      phase, in comparison with its beta-octyl glucoside solution. In these
      experiments, native LH2 and LH2 labeled by a fluorescent marker were used. The
      results indicate that the inclusion of LH2 into the cubic phase induced
      modifications in the carotenoid and B800 binding sites. Despite these significant
      perturbations, the protein seems to keep an oligomeric structure. The relevance
      of these observations for the possible crystallization of this protein in the
      cubic phase is discussed.

PMID- 11509375
TI  - The Fe(2+)-His(F8) Raman band shape of deoxymyoglobin reveals taxonomic
      conformational substates of the proximal linkage.
AB  - The band shape of the Raman line attributed to the Fe(2+)-N(epsilon)(His(F8))
      stretching mode in deoxymyoglobin contains significant information on the nature
      of the Fe-His proximal linkage. Raman lines appearing close to it, however,
      obscure the true line profile. To isolate this from its accompanying lines we use
      its isotopic shift of approximately 1 cm(-1) when (56)Fe in natural-abundance
      deoxymyoglobin is substituted by (54)Fe. This enables us to isolate the true line
      shape. We have measured this line shape in sperm whale myoglobin dissolved in a
      66% vol/vol glycerol/water solution for nine temperatures from 10 K to 300 K. The
      nu(Fe-His) band shows a complex temperature-dependent profile, with a shoulder on
      its high-frequency wing, which becomes more prominent with increasing
      temperature. Detailed analysis reveals that the band is composed of five distinct
      lines attributable to taxonomic conformational substates of the nu(Fe-His)
      linkage. These are in thermodynamic equilibrium above the glass transition
      temperature T(f) but freeze in into the thermodynamic distribution at T(f) for
      lower temperatures. Alternative models that try to explain the nu(Fe-His) band
      shape by either an anharmonic coupling of the nu(Fe-His) to a low-frequency heme
      doming mode or by conformational substates related to a Gaussian distribution of
      iron out-of-plane displacements are at variance with the distinct features
      observed experimentally.

PMID- 11509376
TI  - Contribution of translational and rotational motions to molecular association in
      aqueous solution.
AB  - Much uncertainty and controversy exist regarding the estimation of the enthalpy,
      entropy, and free energy of overall translational and rotational motions of
      solute molecules in aqueous solutions, quantities that are crucial to the
      understanding of molecular association/recognition processes and structure-based
      drug design. A critique of the literature on this topic is given that leads to a
      classification of the various views. The major stumbling block to experimentally
      determining the translational/rotational enthalpy and entropy is the elimination
      of vibrational perturbations from the measured effects. A solution to this
      problem, based on a combination of energy equi-partition and enthalpy-entropy
      compensation, is proposed and subjected to verification. This method is then
      applied to analyze experimental data on the dissociation/unfolding of dimeric
      proteins. For one translational/rotational unit at 1 M standard state in aqueous
      solution, the results for enthalpy (H degrees (tr)), entropy (S degrees (tr)),
      and free energy (G degrees (tr)) are H (degrees) (tr) = 4.5 +/- 1.5RT, S
      (degrees) (tr) = 5 +/- 4R, and G (degrees) (tr) = 0 +/- 5RT. Therefore, the
      overall translational and rotational motions make negligible contribution to
      binding affinity (free energy) in aqueous solutions at 1 M standard state.

PMID- 11509377
TI  - Mechanics and multiple-particle tracking microheterogeneity of alpha-actinin
      cross-linked actin filament networks.
AB  - Cell morphology is controlled by the actin cytoskeleton organization and
      mechanical properties, which are regulated by the available contents in actin and
      actin regulatory proteins. Using rheometry and the recently developed multiple
      particle tracking method, we compare the mechanical properties and
      microheterogeneity of actin filament networks containing the F-actin cross
      linking protein alpha-actinin. The elasticity of F-actin/alpha-actinin networks
      increases with actin concentration more rapidly for a fixed molar ratio of actin
      to alpha-actinin than in the absence of alpha-actinin, for networks of fixed
      alpha-actinin concentration and of fixed actin concentration, but more slowly
      than theoretically predicted for a homogeneous cross-linked semiflexible polymer
      network. These rheological measurements are complemented by multiple-particle
      tracking of fluorescent microspheres imbedded in the networks. The distribution
      of the mean squared displacements of these microspheres becomes progressively
      more asymmetric and wider for increasing concentration in alpha-actinin and, to a
      lesser extent, for increasing actin concentration, which suggests that F-actin
      networks become progressively heterogeneous for increasing protein content. This
      may explain the slower-than-predicted rise in elasticity of F-actin/alpha-actinin
      networks. Together these in vitro results suggest that actin and alpha-actinin
      provides the cell with an unsuspected range of regulatory pathways to modulate
      its cytoskeleton's micromechanics and local organization in vivo.

PMID- 11509378
TI  - Evidence that the 127-164 region of prion proteins has two equi-energetic
      conformations with beta or alpha features.
AB  - Prion proteins cause neurodegenerative illnesses in humans and animals. The
      diseases are associated with a topological change from a predominantly alpha
      (PrP(C)) to beta-sheet (PrP(Sc)) structure. Many studies have focused on the
      minimum sequence requirements and key events for developing or transmitting
      disease. Here, we report on the application of molecular modeling studies to
      predict the lowest-energy conformations for five fragments in solution at pH 7.
      We show that PrP(143-158) adopts a helix, the model PrP(106-126), PrP(142-167),
      and PrP(143-178) peptides have a clear preference for a variety of beta-sheet
      structures, whereas PrP(127-164) has two iso-energetic conformations with all
      beta or alphabeta native-like structures. Such a finding for PrP(127-164), which
      explains a large body of experimental data, including the location of all
      mutations causing prion diseases, may have important implications for triggering
      or propagating the topological change.

PMID- 11509379
TI  - Radially softening diffusive motions in a globular protein.
AB  - Molecular dynamics simulation, quasielastic neutron scattering and analytical
      theory are combined to characterize diffusive motions in a hydrated protein, C
      phycocyanin. The simulation-derived scattering function is in approximate
      agreement with experiment and is decomposed to determine the essential
      contributions. It is found that the geometry of the atomic motions can be modeled
      as diffusion in spheres with a distribution of radii. The time dependence of the
      dynamics follows stretched exponential behavior, reflecting a distribution of
      relaxation times. The average side chain and backbone dynamics are quantified and
      compared. The dynamical parameters are shown to present a smooth variation with
      distance from the core of the protein. Moving outward from the center of the
      protein there is a progressive increase of the mean sphere size, accompanied by a
      narrowing and shifting to shorter times of the relaxation time distribution. This
      smooth, "radially softening" dynamics may have important consequences for protein
      function. It also raises the possibility that the dynamical or "glass" transition
      with temperature observed experimentally in proteins might be depth dependent,
      involving, as the temperature decreases, progressive freezing out of the
      anharmonic dynamics with increasing distance from the center of the protein.

PMID- 11509380
TI  - Structure of type I antifreeze protein and mutants in supercooled water.
AB  - Many organisms are able to survive subzero temperatures at which bodily fluids
      would normally be expected to freeze. These organisms have adapted to these lower
      temperatures by synthesizing antifreeze proteins (AFPs), capable of binding to
      ice, which make further growth of ice energetically unfavorable. To date, the
      structures of five AFPs have been determined, and they show considerable sequence
      and structural diversity. The type I AFP reveals a single 37-residue alpha
      helical structure. We have studied the behavior of wild-type type I AFP and two
      "inactive" mutants (Ala17Leu and Thr13Ser/Thr24Ser) in normal and supercooled
      solutions of H(2)O and deuterium oxide (D(2)O) to see if the structure at
      temperatures below the equilibrium freezing point is different from the structure
      observed at above freezing temperatures. Analysis of 1D (1)H- and (13)C-NMR
      spectra illustrate that all three proteins remain folded as the temperature is
      lowered and even seem to become more alpha-helical as evidenced by (13)C(alpha)
      NMR chemical shift changes. Furthermore, (13)C-T(2) NMR relaxation measurements
      demonstrate that the rotational correlation times of all three proteins behave in
      a predictable manner under all temperatures and conditions studied. These data
      have important implications for the structure of the AFP bound to ice as well as
      the mechanisms for ice-binding and protein oligomerization.

PMID- 11509381
TI  - Conformation of alamethicin in oriented phospholipid bilayers determined by (15)N
      solid-state nuclear magnetic resonance.
AB  - The conformation of the 20-residue antibiotic ionophore alamethicin in
      macroscopically oriented phospholipid bilayers has been studied using (15)N solid
      state nuclear magnetic resonance (NMR) spectroscopy in combination with molecular
      modeling and molecular dynamics simulations. Differently (15)N-labeled variants
      of alamethicin and an analog with three of the alpha-amino-isobutyric acid
      residues replaced by alanines have been investigated to establish experimental
      structural constraints and determine the orientation of alamethicin in hydrated
      phospholipid (dimyristoylphosphatidylcholine) bilayers and to investigate the
      potential for a major kink in the region of the central Pro(14) residue. From the
      anisotropic (15)N chemical shifts and (1)H-(15)N dipolar couplings determined for
      alamethicin with (15)N-labeling on the Ala(6), Val(9), and Val(15) residues and
      incorporated into phospholipid bilayer with a peptide:lipid molar ratio of 1:8,
      we deduce that alamethicin has a largely linear alpha-helical structure spanning
      the membrane with the molecular axis tilted by 10-20 degrees relative to the
      bilayer normal. In particular, we find compatibility with a straight alpha-helix
      tilted by 17 degrees and a slightly kinked molecular dynamics structure tilted by
      11 degrees relative to the bilayer normal. In contrast, the structural
      constraints derived by solid-state NMR appear not to be compatible with any of
      several model structures crossing the membrane with vanishing tilt angle or the
      earlier reported x-ray diffraction structure (Fox and Richards, Nature. 300:325
      330, 1982). The solid-state NMR-compatible structures may support the formation
      of a left-handed and parallel multimeric ion channel.

PMID- 11509382
TI  - Decomposition of protein tryptophan fluorescence spectra into log-normal
      components. I. Decomposition algorithms.
AB  - Two algorithms of decomposition of composite protein tryptophan fluorescence
      spectra were developed based on the possibility that the shape of elementary
      spectral component could be accurately described by a uniparametric log-normal
      function. The need for several mathematically different algorithms is dictated by
      the fact that decomposition of spectra into widely overlapping smooth components
      is a typical incorrect problem. Only the coincidence of components obtained with
      various algorithms can guarantee correctness and reliability of results. In this
      paper we propose the following algorithms of decomposition: (1) the SImple
      fitting procedure using the root-Mean-Square criterion (SIMS) operating with
      either individual emission spectra or sets of spectra measured with various
      quencher concentrations; and (2) the pseudo-graphic analytical procedure using a
      PHase plane in coordinates of normalized emission intensities at various
      wavelengths (wavenumbers) and REsolving sets of spectra measured with various
      Quencher concentrations (PHREQ). The actual experimental noise precludes
      decomposition of protein spectra into more than three components.

PMID- 11509383
TI  - Decomposition of protein tryptophan fluorescence spectra into log-normal
      components. II. The statistical proof of discreteness of tryptophan classes in
      proteins.
AB  - The physical causes for wide variation of Stokes shift values in emission spectra
      of tryptophan fluorophores in proteins have been proposed in the model of
      discrete states (Burstein, E. A., N. S. Vedenkina, and M. N. Ivkova. 1973.
      Photochem. Photobiol. 18:263-279; Burstein, E. A. 1977a. Intrinsic Protein
      Luminescence (The Nature and Application). In Advances in Science and Technology
      (Itogi Nauki i Tekhniki), Biophysics Vol. 7. VINITI, Moscow [In Russian];
      Burstein, E. A. 1983. Molecular Biology (Moscow) 17:455-467 [In Russian; English
      translation]). It was assumed that the existence of the five most probable
      spectral classes of emitting tryptophan residues and differences among the
      classes were analyzed in terms of various combinations of specific and universal
      interactions of excited fluorophores with their environment. The development of
      stable algorithms of decomposition of tryptophan fluorescence spectra into log
      normal components gave us an opportunity to apply two mathematically different
      algorithms, SImple fitting with Mean-Square criterion (SIMS) and PHase-plot-based
      REsolving with Quenchers (PHREQ) for the decomposition of a representative set of
      emission spectra of proteins. Here we present the results of decomposition of
      tryptophan emission spectra of >100 different proteins, some in various
      structural states (native and denatured, in complexes with ions or organic
      ligands, in various pH-induced conformations, etc.). Analysis of the histograms
      of occurrence of >300 spectral log-normal components with various maximum
      positions confirmed the statistical discreteness of several states of emitting
      tryptophan fluorophores in proteins.

PMID- 11509384
TI  - Decomposition of protein tryptophan fluorescence spectra into log-normal
      components. III. Correlation between fluorescence and microenvironment parameters
      of individual tryptophan residues.
AB  - In our previous paper (Reshetnyak, Ya. K., and E. A. Burstein. 2001. Biophys. J.
      81:1710-1734) we confirmed the existence of five statistically discrete classes
      of emitting tryptophan fluorophores in proteins. The differences in fluorescence
      properties of tryptophan residues of these five classes reflect differences in
      interactions of excited states of tryptophan fluorophores with their
      microenvironment in proteins. Here we present a system of describing physical and
      structural parameters of microenvironments of tryptophan residues based on
      analysis of atomic crystal structures of proteins. The application of
      multidimensional statistical methods of cluster and discriminant analyses for the
      set of microenvironment parameters of 137 tryptophan residues of 48 proteins with
      known three-dimensional structures allowed us to 1) demonstrate the discrete
      nature of ensembles of structural parameters of tryptophan residues in proteins;
      2) assign spectral components obtained after decomposition of tryptophan
      fluorescence spectra to individual tryptophan residues; 3) find a correlation
      between spectroscopic and physico-structural features of the microenvironment;
      and 4) reveal differences in structural and physical parameters of the
      microenvironment of tryptophan residues belonging to various spectral classes.

PMID- 11509385
TI  - Simultaneous measurement of Ca2+ and cellular dynamics: combined scanning ion
      conductance and optical microscopy to study contracting cardiac myocytes.
AB  - We have developed a distance modulated protocol for scanning ion conductance
      microscopy to provide a robust and reliable distance control mechanism for
      imaging contracting cells. The technique can measure rapid changes in cell height
      from 10 nm to several micrometers, with millisecond time resolution. This has
      been demonstrated on the extreme case of a contracting cardiac myocyte. By
      combining this method with laser confocal microscopy, it was possible to
      simultaneously measure the nanometric motion of the cardiac myocyte, and the
      local calcium concentration just under the cell membrane. Despite large cellular
      movement, simultaneous tracking of the changes in cell height and measurement of
      the intracellular Ca2+ near the cell surface is possible while retaining the cell
      functionality.

PMID- 11509386
TI  - Complex homogeneous and heterogeneous fluorescence anisotropy decays: enhancing
      analysis accuracy.
AB  - In biological macromolecules, fluorophores often exhibit multiple depolarizing
      motions that require multiple lifetimes and rotational relaxation times to define
      fluorescence intensity and anisotropy decays. The related analysis of time
      correlated single-photon counting data becomes uncertain due to the multitude of
      decay parameters and numerical sensitivity to deconvolution of the instrument
      response function (IRF) via discretization of integrals. By using simulations we
      show that improved discretizations based on quadratic and cubic local
      approximations of the IRF yield more accurate estimation of short rotational
      relaxation times and lifetimes than the commonly used Grinvald-Steinberg
      discretization, which in turn appears more reliable than two discretizations
      based on linear local approximations of the IRF. In addition, our simulation
      suggests that cubic approximation is the most advantageous in discriminating
      complex heterogeneous and homogeneous anisotropy decay. We show that among three
      different information criteria, the Akaike information criterion is best suited
      for detection of heterogeneity in rotational relaxation times. It is capable of
      detecting heterogeneity even when anisotropy decay appears homogeneous within
      statistical errors of estimation.

PMID- 11509387
TI  - Light-induced flickering of DsRed provides evidence for distinct and
      interconvertible fluorescent states.
AB  - Green fluorescent protein (GFP) from jellyfish Aequorea victoria, the powerful
      genetically encoded tag presently available in a variety of mutants featuring
      blue to yellow emission, has found a red-emitting counterpart. The recently
      cloned red fluorescent protein DsRed, isolated from Discosoma corals (), with its
      emission maximum at 583 nm, appears to be the long awaited tool for multi-color
      applications in fluorescence-based biological research. Studying the emission
      dynamics of DsRed by fluorescence correlation spectroscopy (FCS), it can be
      verified that this protein exhibits strong light-dependent flickering similar to
      what is observed in several yellow-shifted mutants of GFP. FCS data recorded at
      different intensities and excitation wavelengths suggest that DsRed appears under
      equilibrated conditions in at minimum three interconvertible states, apparently
      fluorescent with different excitation and emission properties. Light absorption
      induces transitions and/or cycling between these states on time scales of several
      tens to several hundreds of microseconds, dependent on excitation intensity. With
      increasing intensity, the emission maximum of the static fluorescence
      continuously shifts to the red, implying that at least one state emitting at
      longer wavelength is preferably populated at higher light levels. In close
      resemblance to GFP, this light-induced dynamic behavior implies that the
      chromophore is subject to conformational rearrangements upon population of the
      excited state.

PMID- 11509388
TI  - Cell traction forces on soft biomaterials. I. Microrheology of type I collagen
      gels.
AB  - A laser-trap microrheometry technique was used to determine the local shear
      moduli of Type I collagen gels. Embedded 2.1 microm polystyrene latex particles
      were displaced 10-100 nm using a near-infrared laser trap with a trap constant of
      0.0001 N/m. The trap was oscillated transversely +/- 200 nm using a refractive
      glass plate mounted on a galvanometric scanner. The displacement of the
      microspheres was in phase with the movement of the laser trap at frequencies less
      than 1 rad/s, indicating that at least locally, the gels behaved as elastic
      media. The local shear modulus was measured at various positions throughout the
      gel, and, for gels at 2.3 mg/mL and 37 degrees C, values ranged from G = 3 to 80
      Pa. The average shear modulus G = 55 Pa, which compares well with measurements
      from parallel plate rheometry.

PMID- 11509389
TI  - Thermodynamics of specific and nonspecific DNA binding by two DNA-binding domains
      conjugated to fluorescent probes.
AB  - The complexes designed in this work combine the sequence-specific binding
      properties of helix-turn-helix DNA-binding motifs with intercalating cyanine
      dyes. Thermodynamics of the Hin recombinase and Tc3 transposase DNA-binding
      domains with and without the conjugated dyes were studied by fluorescence
      techniques to determine the contributions to specific and nonspecific binding in
      terms of the polyelectrolyte and hydrophobic effects. The roles of the
      electrostatic interactions in binding to the cognate and noncognate sequences
      indicate that nonspecific binding is more sensitive to changes in salt
      concentration, whereas the change in the heat capacity shows a greater
      sensitivity to temperature for the sequence-specific complexes in each case. The
      conjugated dyes affect the Hin DNA-binding domain by acting to anchor a short
      stretch of amino acids at the N-terminal end into the minor groove. In contrast,
      the N-terminal end of the Tc3 DNA-binding domain is bound in a well-ordered
      fashion to the DNA even in the absence of the conjugated dye. The conjugated dye
      and the DNA-binding domain portions of each conjugate bind noncooperatively to
      the DNA. The characteristic thermodynamic parameters of specific and nonspecific
      DNA binding by each of the DNA-binding domains and their respective conjugates
      are presented.

PMID- 11509391
TI  - Ionising Radiation (Medical Exposure) Regulations: impact on clinical radiology.

PMID- 11509390
TI  - A mathematical model of the kinetics of beta-amyloid fibril growth from the
      denatured state.
AB  - Spontaneous conversion of beta-amyloid peptide (Abeta) from soluble monomer to
      insoluble fibril may underlie the neurodegeneration associated with Alzheimer's
      disease. A complete description of Abeta self-association kinetics requires
      identification of the oligomeric species present and the pathway of association,
      as well as quantitation of rate constants and reaction order. Abeta was rendered
      monomeric and denatured by dissolution in 8 M urea, pH 10. "Refolding" and
      fibrillization were initiated by rapid dilution into phosphate-buffered saline,
      pH 7.4. The kinetics of growth were followed at three different concentrations,
      using size exclusion chromatography, dynamic light scattering, and static light
      scattering. A multi-step pathway for fibril formation and growth was postulated.
      This pathway included 1) rapid commitment to either stable monomer/dimer or
      unstable intermediate, 2) cooperative association of intermediate into a
      multimeric "nucleus," 3) elongation of the "nucleus" into filaments via addition
      of intermediate, 4) lateral aggregation of filaments into fibrils, and 5) fibril
      elongation via end-to-end association. Differential and algebraic equations
      describing this kinetic pathway were derived, and model parameters were
      determined by fitting the data. The utility of the model for identifying toxic
      Abeta oligomeric specie(s) is demonstrated. The model should prove useful for
      designing compounds that inhibit Abeta aggregation and/or toxicity.

PMID- 11509392
TI  - Imaging in epilepsy: a paediatric perspective.
AB  - Assessment of a child with epilepsy involves a number of key stages, the most
      crucial being clinical evaluation where the presence of seizure activity and
      seizure type is identified. Subsequent imaging is not required in all children.
      In those selected for further investigation, imaging techniques are broadly
      divided into structural and functional studies. MRI currently provides the best
      structural data, with nuclear medicine and specialized MR techniques giving
      supportive functional information. CT now has a much diminished role. This review
      highlights the role of different imaging modalities in the investigation of
      childhood epilepsy, as well as some of the practicalities of imaging children,
      and areas where recent advances have been made. It is hoped that the overview and
      information provided will help both the specialist and the general radiologist
      make informed decisions regarding how to best image a child with epilepsy.

PMID- 11509393
TI  - Colour flow Doppler ultrasound of the carotid bifurcation: can it replace routine
      angiography before carotid endarterectomy?
AB  - The objective of this study was to assess the diagnostic accuracy of colour flow
      Doppler ultrasound (CFD) and its potential to replace digital subtraction
      angiography (DSA) before carotid endarterectomy (CEA). All patients undergoing
      CFD of the carotid bifurcation in our department over a period of 1-1/2 years for
      whom both CFD and DSA results were available were included in the study. We
      evaluated the feasibility of CFD, its diagnostic accuracy and its potential to
      diagnose clinically significant stenosis (50%, 70% and 90% NASCET type diameter
      stenosis) compared with DSA. 225 carotid bifurcations in 116 patients met the
      criteria for evaluation (biplane arterial DSA without superimposition). Data
      analysis yielded the following diagnostic performance of CFD: sensitivity for a
      50% stenosis 91.4% (95% confidence interval (CI) 83.3--96.2%), specificity 93.2%
      (95% CI 87.1--96.8%) and accuracy 92.4% (95% CI 88.4--95.4%); sensitivity for a
      70% stenosis 89.2% (95% CI 81.9--94.1%), specificity 96.2% (95% CI 90.5--98.6%)
      and accuracy 92.4% (95% CI 88.4--95.4%). In 9 of 116 cases, carotid angiography
      was used to evaluate inconclusive CFD results. DSA disclosed relevant information
      not suspected by CFD in only 1 of the 116 cases. Thus, 91% (106/116) of the
      angiographies could have been dispensed with without loss of information. One
      major stroke occurred during diagnostic DSA. We conclude that DSA of the carotid
      arteries is unnecessary when CFD is unequivocal. The diagnostic gain of DSA must
      be counterweighted against its potential risks.

PMID- 11509394
TI  - Pyelocalyceal diverticulum: the imaging spectrum with emphasis on the ultrasound
      features.
AB  - Clinical and imaging data of 11 patients with pyelocalyceal diverticulum were
      retrospectively examined. Four patients suffered from ipsilateral flank pain, one
      from recurrent urinary tract infection and the other six from unrelated symptoms.
      All patients underwent ultrasound as the initial imaging study. In two cases
      ultrasound was the only examination performed. Additional imaging studies were
      obtained in the other nine patients (abdominal radiography in six cases,
      intravenous urography (IVU) in five and CT in four). Ultrasound suggested the
      diagnosis of pyelocalyceal diverticulum in eight cases owing to the presence of
      echogenic and mobile material within the cyst-like lesion. In three cases the
      ultrasound appearance was similar and indistinguishable from a simple cyst and
      the diagnosis was made by another imaging study IVU in two cases and CT in one).
      We suggest that ultrasound examination is the best imaging method for the
      diagnosis of a pyelocalyceal diverticulum, and no further imaging modalities are
      required when mobile echogenic material is seen. In uncertain cases, another
      relatively inexpensive imaging study should be added such as abdominal
      radiography or IVU.

PMID- 11509396
TI  - A practical approach to the first iteration in the optimization of radiation dose
      and image quality in CT: estimates of the collective dose savings achieved.
AB  - CT is a diagnostic imaging modality giving higher patient dose in comparison with
      other radiological procedures. It contributed an estimated 20% to the collective
      effective dose to the UK population from medical X-rays in 1990, rising to an
      estimated 40% in 1999. Tremendous national effort has been expended in reducing
      patient doses from other radiological procedures with considerable success, but
      much of the collective dose reduction achieved has been offset by a corresponding
      increase in the collective dose from CT. Over a period of about 2 years,
      following the installation of a helical CT scanner, CT scan parameters in this
      hospital have been adjusted with the aim of working towards optimization of image
      quality and patient dose. A 33% reduction in annual collective effective dose has
      been achieved, from about 16.5 manSv to 11 manSv. However, despite this dose
      reduction, the annual collective effective dose to our sub-population is 2.8
      times the value 9 years ago. The increase is almost entirely the result of an
      increased application of CT; 6149 examinations per annum in 1999 compared with
      2210 in 1991. The crucial importance of reducing patient doses from this modality
      is discussed. Indicative effective doses and image noise values are presented for
      examination protocols approaching optimization.

PMID- 11509395
TI  - Evaluation of bone mineral density by quantitative ultrasound of bone in 16,862
      subjects during routine health examination.
AB  - Caucasians and Asians are among those with the highest risk for involutional
      osteoporosis. To obtain accurate data about the prevalence of osteoporosis or
      osteopenia in different age groups, a large epidemiological study is necessary.
      Quantitative ultrasound (QUS) of bone is a promising technique in assessing bone
      microarchitecture in addition to bone mass. This study had two aims. The first
      was to establish bone mineral density (BMD) using QUS in subjects with no obvious
      disease undergoing routine health examination. The second was to determine risk
      factors for osteoporosis in Taiwan in order that better prevention and treatment
      measures may be provided for these patients. A prospective study of the risk
      factors for fracture was conducted in the health examination division of Chang
      Gung Medical Center in Linkou, Taiwan, from January 1996 to December 1997.
      Broadband ultrasound attenuation of the right heel was measured with an achilles
      bone densitometer (Lunar, Nauheim, Germany). A total of 16,862 subjects were
      examined, including 9,314 women (mean age 51.5+/-11.7 years) and 7,548 men (mean
      age 51.1+/-12.1 years). The incidence of osteoporosis in all subjects increased
      from 1.13% in the 21--30-year-old age group to 54.55% in those over 80 years of
      age. 12.02% of the subjects had osteoporosis and 34.45% had osteopenia. From
      multivariate analysis, bone density evaluated by QUS showed a relationship with
      age, gender, body mass index, waist/hip ratio, smoking and frequency of exercise.
      In conclusion, BMD evaluated by QUS is not found to be higher in Taiwan than
      elsewhere. The role of QUS in predicting fractures in Taiwan requires further
      investigation.

PMID- 11509397
TI  - Procedure for quantitatively assessing automatic exposure control in mammography:
      a study of the GE Senographe 600 TS.
AB  - The correct operation of a mammography system's automatic exposure control system
      (AEC) is essential if mammograms are to be produced with a suitable film
      exposure. A methodology has been developed that allows the performance of the AEC
      to be assessed quantitatively using clinical films. By digitizing mammograms, the
      mean optical density (OD) in the main breast region and in a region of interest
      corresponding to the position of the AEC detector are evaluated for each film,
      together with the area of the main breast. Using these data it is possible to
      determine the relationships between the mean OD, breast size and AEC detector
      position. The performance of the AEC on a GE Senographe 600 TS system was
      investigated. The study found that there is a tendency to underexpose smaller
      breasts, i.e. with an area less than approximately 4000 mm(2). This is equivalent
      to a compressed tissue width of approximately 60---80 mm. The difference in mean
      OD between the mammograms of small and large breasts was up to 0.7 OD. Provided
      the sensitive area of the AEC detector is known, this method of assessing AEC
      performance can be used with any mammography system.

PMID- 11509398
TI  - ROC curve analysis of lesion detectability on phantoms: comparison of digital
      spot mammography with conventional spot mammography.
AB  - Although conventional screen--film mammography has excellent spatial resolution
      and is commonly used as a screening tool, certain inherent limitations prevent
      its further improvement. New digital mammography techniques, despite lower
      spatial resolution than screen--film mammography, may overcome these limitations.
      This study compared lesion detectability between charge coupled device-based
      digital spot mammography and conventional spot mammography. A total of 100 sets
      of images of specially designed breast phantoms was acquired, with variable
      background achieved by overlapping several layers of grapefruit fibre on a 4 cm
      thick lucite slab, using both modalities. 75 sets were "normal" images and 25
      sets were images with simulated lesions. Four radiologists assessed the images
      according to a five-point confidence scale. The results were used to construct
      receiver operating characteristic curves. No statistical difference was observed
      between the two sets of curves for individual radiologists as well as pooled
      data. The lower spatial resolution of digital mammography was compensated for by
      its higher contrast sensitivity relative to conventional spot mammography.

PMID- 11509399
TI  - Equivalent dose to the fetus from occupational exposure of pregnant staff in
      diagnostic radiology.
AB  - The protection of the unborn children of pregnant women from ionizing radiations
      is very important because the fetus is particularly vulnerable to the effects of
      ionizing radiation. From the radiation protection perspective, the International
      Commission on Radiological Protection regards the unborn child as a member of the
      public when considering the occupational exposure of pregnant workers. The
      determination of the equivalent dose to the unborn child in diagnostic radiology
      is of interest as a basis for risk estimates from occupational exposures of the
      pregnant worker. In this paper, coefficients for converting dosemeter readings to
      equivalent dose to the fetus have been calculated using Monte Carlo simulation. X
      ray transport was simulated by tracing individual photons through soft tissue
      phantoms. Equivalent dose to the uterus was used to simulate the equivalent dose
      to the fetus during the first 2 months of pregnancy. The Monte Carlo model was
      validated experimentally by direct measurements made in an Alderson female Rando
      phantom for a range of irradiation conditions. The two sets of data indicated
      good agreement with the Monte Carlo results, being relatively greater than the
      experimental results to a maximum of about 15%.

PMID- 11509400
TI  - Radiotherapy for a solitary brain metastasis during pregnancy: a method for
      reducing fetal dose.
AB  - A patient presented during the second half of pregnancy with a solitary brain
      metastasis from lung cancer. This case shows that, using a new patient position,
      it is possible to shield the fetus efficiently. This new method consisted of
      whole brain irradiation with parallel pair treatment by lateral fields with the
      patient in a supine position with maximal neck extension. The dose to the fetus
      has been considerably reduced (0.3 cGy total dose) compared with previous
      techniques. The prescribed tumour dose was 30 Gy.

PMID- 11509401
TI  - MR diffusion tensor imaging of white matter tract disruption in stroke at 3 T.
AB  - Recent advances in MR diffusion weighted imaging (DWI) enable the identification
      of anisotropic white matter tracts with diffusion tensor imaging (DTI). We aimed
      to use a novel DTI technique to safely study patients with recent stroke in a
      high field (3 T) MR machine with its intrinsically higher spatial resolution and
      signal-to-noise ratio. Of ten patients studied, six had disruption of white
      matter tracts as determined by DTI. A further patient had distortion of white
      matter tracts around an infarct rather than actual disruption of the tracts
      themselves. The lack of tract destruction may imply a beneficial prognosis,
      information that is not available with conventional DWI.

PMID- 11509402
TI  - Diagnostic angiography performed by nurses.
AB  - The aim of this study was to assess the feasibility of a nurse performing
      diagnostic angiography. After a theoretical and practical training course on the
      techniques of arterial catheterization, the nurse performed diagnostic
      angiography under supervision on 68 patients. Patients with impalpable femoral
      pulses or scarred groins as well as obese patients were excluded. Successful
      arterial catheterization was achieved in 58 (85%) patients. Complications were
      limited to a severe haematoma requiring surgery in one patient and seven minor
      self-limiting haematomas. On this evidence, it is feasible and safe for
      appropriately trained nurses to perform angiography in radiology departments that
      have limited radiology staffing levels and no non-invasive alternations to
      catheter-based angiography.

PMID- 11509403
TI  - Cystic malignant fibrous histiocytoma of the gastrocolic ligament.
AB  - A case of malignant fibrous histiocytoma (MFH) of the gastrocolic ligament is
      presented. It appeared as a huge, thin walled cystic tumour in the upper
      abdominal cavity on CT. Barium studies showed splaying of the stomach and
      transverse colon by the mass. 1 year after resection of the cystic tumour,
      recurrence occurred at the greater curvature of the stomach and in the liver,
      with a cystic appearance similar to the primary tumour. To our knowledge, the CT
      appearance of primary cystic MFH of the gastrocolic ligament has not been
      previously documented.

PMID- 11509404
TI  - CT findings of portal vein aneurysm caused by gastric adenocarcinoma invading the
      portal vein.
AB  - The known causes of acquired origin portal vein aneurysm are portal hypertension,
      pancreatitis and trauma. We describe the CT findings of an additional cause of
      acquired origin portal vein aneurysm, namely gastric adenocarcinoma invading the
      portal venous system.

PMID- 11509405
TI  - Intralobar bronchopulmonary sequestration: evidence of air trapping shown by
      dynamic xenon-133 SPECT.
AB  - Dynamic single photon emission computed tomography with xenon-133 gas in a 29
      year-old male patient showed xenon-133 retention within an intralobar
      bronchopulmonary sequestration (BPS) with a focal hyperlucent lung area on CT.
      Left lower lobectomy showed no fistulous connection between the anomalous and
      normal bronchial trees, but non-contiguous, incompletely developed visceral
      pleura between the sequestration and the adjacent normally ventilated lung. These
      features strongly support the role of intralobar collateral air drift and air
      trapping in producing secondary changes of a focal hyperlucent lung area in BPS.

PMID- 11509406
TI  - Imaging of giant tumours involving the anterior skull base.
AB  - Tumours involving the anterior skull base are a challenge in diagnosis and
      treatment. They may arise from the bony skull base itself, intracranially or from
      the sinonasal tract and orbit. It is often difficult to determine the site of
      origin of giant tumours as anatomical boundaries are frequently breached.
      Accurate imaging evaluation is useful in planning treatment and may help in the
      differential diagnosis. We review those CT and MRI features of giant anterior
      cranial fossa tumours which may be helpful in identifying a pre-operative
      diagnosis.

PMID- 11509407
TI  - Pulsatile tinnitus.

PMID- 11509408
TI  - A simple method for verifying spinal cord position on oblique simulation and
      portal verification radiographs of the chest.

PMID- 11509409
TI  - Does exposure to landfill waste harm the fetus? Perhaps, but more evidence is
      needed.

PMID- 11509410
TI  - Improving endothelial vasomotor function.

PMID- 11509411
TI  - Bacteriotherapy: the time has come.

PMID- 11509412
TI  - Phytoestrogen therapy for menopausal symptoms?

PMID- 11509413
TI  - Referral of Dr Peter Mansfield to the GMC.

PMID- 11509414
TI  - President Bush sidesteps critics in stem cell debate.

PMID- 11509416
TI  - Trust defends decision to retain private beds at Heart Hospital.

PMID- 11509417
TI  - "Video pill" may supplement standard endoscopy.

PMID- 11509418
TI  - Exercise and diet reduce risk of diabetes, US study shows.

PMID- 11509419
TI  - Bayer decides to withdraw cholesterol lowering drug.

PMID- 11509421
TI  - Why a 1940s medical committee should not be forgotten.

PMID- 11509422
TI  - Mortality and smoking in Hong Kong: case-control study of all adult deaths in
      1998.
AB  - OBJECTIVE: To assess the mortality currently associated with smoking in Hong
      Kong, and, since cigarette consumption reached its peak 20 years earlier in Hong
      Kong than in mainland China, to predict mortality in China 20 years hence.
      DESIGN: Case-control study. Past smoking habits of all Chinese adults in Hong
      Kong who died in 1998 (cases) were sought from those registering the death.
      SETTING: All the death registries in Hong Kong. PARTICIPANTS: 27 507 dead cases
      (81% of all registered deaths) and 13 054 live controls aged >/=35 years. MAIN
      OUTCOME MEASURES: Mortality from all causes and from specific causes. RESULTS: In
      men aged 35-69 the adjusted risk ratios (and 95% confidence intervals) comparing
      smokers with non-smokers were 1.92 (1.70 to 2.16) for all deaths, 2.22 (1.94 to
      2.55) for neoplastic deaths, 2.60 (2.10 to 3.21) for respiratory deaths
      (including tuberculosis, risk ratio 2.54), and 1.68 (1.43 to 1.97) for vascular
      deaths (each P<0.0001). In women aged 35-69 the corresponding risk ratios were
      1.62 (1.40 to 1.88) for all deaths, 1.60 (1.33 to 1.93) for neoplastic deaths,
      3.13 (2.21 to 4.44) for respiratory deaths, and 1.55 (1.20 to 1.99) for vascular
      deaths (each P<0.001). If these associations with smoking are largely or wholly
      causal then, among all registered deaths at ages 35-69 in 1998, tobacco caused
      about 33% (2534/7588) of all male deaths and 5% (169/3341) of all female deaths
      (hence 25% of all deaths at these ages). At older ages tobacco seemed to be the
      cause of 15% (3017/20 420) of all deaths. CONCLUSIONS: Among middle aged men the
      proportion of deaths caused by smoking is more than twice as big in Hong Kong now
      (33%) as in mainland China 10 years earlier. This supports predictions of a large
      increase in tobacco attributable mortality in China as a whole.

PMID- 11509424
TI  - Risk of adverse birth outcomes in populations living near landfill sites.
AB  - OBJECTIVE: To investigate the risk of adverse birth outcomes associated with
      residence near landfill sites in Great Britain. DESIGN: Geographical study of
      risks of adverse birth outcomes in populations living within 2 km of 9565
      landfill sites operational at some time between 1982 and 1997 (from a total of 19
      196 sites) compared with those living further away. SETTING: Great Britain.
      SUBJECTS: Over 8.2 million live births, 43 471 stillbirths, and 124 597
      congenital anomalies (including terminations). MAIN OUTCOME MEASURES: All
      congenital anomalies combined, some specific anomalies, and prevalence of low and
      very low birth weight (<2500 g and <1500 g). RESULTS: For all anomalies combined,
      relative risk of residence near landfill sites (all waste types) was 0.92 (99%
      confidence interval 0.907 to 0.923) unadjusted, and 1.01 (1.005 to 1.023)
      adjusted for confounders. Adjusted risks were 1.05 (1.01 to 1.10) for neural tube
      defects, 0.96 (0.93 to 0.99) for cardiovascular defects, 1.07 (1.04 to 1.10) for
      hypospadias and epispadias (with no excess of surgical correction), 1.08 (1.01 to
      1.15) for abdominal wall defects, 1.19 (1.05 to 1.34) for surgical correction of
      gastroschisis and exomphalos, and 1.05 (1.047 to 1.055) and 1.04 (1.03 to 1.05)
      for low and very low birth weight respectively. There was no excess risk of
      stillbirth. Findings for special (hazardous) waste sites did not differ
      systematically from those for non-special sites. For some specific anomalies,
      higher risks were found in the period before opening compared with after opening
      of a landfill site, especially hospital admissions for abdominal wall defects.
      CONCLUSIONS: We found small excess risks of congenital anomalies and low and very
      low birth weight in populations living near landfill sites. No causal mechanisms
      are available to explain these findings, and alternative explanations include
      data artefacts and residual confounding. Further studies are needed to help
      differentiate between the various possibilities.

PMID- 11509426
TI  - Maternal and paternal age at delivery, birth order, and risk of childhood onset
      type 1 diabetes: population based cohort study.
AB  - OBJECTIVE: To estimate the associations of maternal and paternal age at delivery
      and of birth order with the risk of childhood onset type 1 diabetes. DESIGN:
      Cohort study by record linkage of the medical birth registry and the national
      childhood diabetes registry in Norway. SETTING: Norway. SUBJECTS: All live births
      in Norway between 1974 and 1998 (1.4 million people) were followed for a maximum
      of 15 years, contributing 8.2 million person years of observation during 1989-98.
      1824 cases of type 1 diabetes diagnosed between 1989 and 1998 were identified.
      MAIN OUTCOME MEASURES: Incidence of type 1 diabetes. RESULTS: There was no
      association between maternal age at delivery and type 1 diabetes among firstborn
      children, but among fourth born children there was a 43.2% increase in incidence
      of diabetes for each five year increase in maternal age (95% confidence interval
      6.4% to 92.6%). Each increase in birth order was associated with a 17.9%
      reduction in incidence (3.2% to 30.4%) when maternal age was 20-24 years, but the
      association was weaker when maternal age was 30 years or more. Paternal age was
      not associated with type 1 diabetes after maternal age was adjusted for.
      CONCLUSIONS: Intrauterine factors and early life environment may influence the
      risk of type 1 diabetes. The relation of maternal age and birth order to risk of
      type 1 diabetes is complex.

PMID- 11509428
TI  - Targeting deprived areas within small areas in Scotland: population study.

PMID- 11509427
TI  - Is it possible to exclude a diagnosis of myocardial damage within six hours of
      admission to an emergency department? Diagnostic cohort study.
AB  - OBJECTIVE: To assess the clinical efficacy and accuracy of an emergency
      department based six hour rule-out protocol for myocardial damage. DESIGN:
      Diagnostic cohort study. SETTING: Emergency department of an inner city
      university hospital. PARTICIPANTS: 383 consecutive patients aged over 25 years
      with chest pain of less than 12 hours' duration who were at low to moderate risk
      of acute myocardial infarction. INTERVENTION: Serial measurements of creatine
      kinase MB mass and continuous ST segment monitoring for six hours with 12 leads.
      MAIN OUTCOME MEASURE: Performance of the diagnostic test against a gold standard
      consisting of either a 48 hour measurement of troponin T concentration or
      screening for myocardial infarction according to the World Health Organization's
      criteria. RESULTS: Outcome of the gold standard test was available for 292
      patients. On the diagnostic test for the protocol, 53 patients had positive
      results and 239 patients had negative results. There were 18 false positive
      results and one false negative result. Sensitivity was 97.2% (95% confidence
      interval 95.0% to 99.0%), specificity 93.0% (90.0% to 96.0%), the negative
      predictive value 99.6%, and the positive predictive value 66.0%. The positive
      likelihood ratio was 13.9 and the negative likelihood ratio 0.03. CONCLUSIONS:
      The six hour rule-out protocol for myocardial infarction is accurate and
      efficacious. It can be used in patients presenting to emergency departments with
      chest pain indicating a low to moderate risk of myocardial infarction.

PMID- 11509429
TI  - Risk of macular degeneration in users of statins: cross sectional study.

PMID- 11509430
TI  - Antenatal detection of HIV: national surveillance and unlinked anonymous survey.

PMID- 11509431
TI  - Prescribing new drugs: qualitative study of influences on consultants and general
      practitioners.
AB  - OBJECTIVE: To explore consultants' and general practitioners' perceptions of the
      factors that influence their decisions to introduce new drugs into their clinical
      practice. DESIGN: Qualitative study using semistructured interviews. Monitoring
      of hospital and general practice prescribing data for eight new drugs. SETTING:
      Teaching hospital and nearby general hospital plus general practices in
      Birmingham. PARTICIPANTS: 38 consultants and 56 general practitioners who
      regularly referred to the teaching hospital. MAIN OUTCOME MEASURES: Reasons for
      prescribing a new drug; sources of information used for new drugs; extent of
      contact between consultants and general practitioners; and amount of study drugs
      used in hospitals and by general practitioners. RESULTS: Consultants usually
      prescribed new drugs only in their specialty, used few new drugs, and used
      scientific evidence to inform their decisions. General practitioners generally
      prescribed more new drugs and for a wider range of conditions, but their approach
      varied considerably both between general practitioners and between drugs for the
      same general practitioner. Drug company representatives were an important source
      of information for general practitioners. Prescribing data were consistent with
      statements made by respondents. CONCLUSIONS: The factors influencing the
      introduction of new drugs, particularly in primary care, are more multiple and
      complex than suggested by early theories of drug innovation. Early experience of
      using a new drug seems to strongly influence future use.

PMID- 11509432
TI  - Fortnightly review: Corticosteroid injections in tendon lesions.

PMID- 11509433
TI  - Lesson of the week: Causes of haematuria in adult polycystic kidney disease.

PMID- 11509434
TI  - Ethical debate: The distinction between withdrawing life sustaining treatment
      under the influence of paralysing agents and euthanasia. Are we treading a fine
      line?

PMID- 11509435
TI  - Mann-Whitney test is not just a test of medians: differences in spread can be
      important.

PMID- 11509437
TI  - Hormonal markers of susceptibility to sexually transmitted infections: are we
      taking them seriously?

PMID- 11509442
TI  - Two faces of nitric oxide: lessons learned from the NOS2 knockout.

PMID- 11509443
TI  - Salt-sensitive hypertension and inducible nitric oxide synthase: form-function
      dichotomy of a coding region mutation, Mutatis mutandis.

PMID- 11509444
TI  - -OONO: rebounding from nitric oxide.

PMID- 11509445
TI  - Phospholipase A(2) in vascular disease.
AB  - Secretory phospholipase A(2) (PLA(2)) can be proatherogenic both in the
      circulation and in the arterial wall. In blood plasma, PLA(2) can modify the
      circulating lipoproteins and so induce formation of small dense LDL particles,
      which are associated with increased risk for cardiovascular disease. In the
      arterial wall, PLA(2) can hydrolyze lipoproteins. The PLA(2)-modified
      lipoproteins bind tightly to extracellular proteoglycans, which may lead to their
      enhanced retention in the arterial wall. The modified lipoproteins may also
      aggregate and fuse, which can lead to accumulation of their lipids within the
      extracellular matrix. The PLA(2)-modified particles are more susceptible to
      further modifications by other enzymes and agents and can be taken up by
      macrophages, leading to accumulation of intracellular lipids. In addition,
      lysophospholipids and free fatty acids, the hydrolysis products of PLA(2),
      promote atherogenesis. Thus, these lipid mediators can be carried, either by the
      PLA(2)-modified lipoproteins themselves or by albumin, into the arterial cells,
      which then undergo functional alterations. This may, in turn, lead to specific
      changes in the extracellular matrix, which increase the retention and
      accumulation of lipoproteins within the matrix. In the present article, we
      discuss the possible actions of PLA(2) enzymes, especially PLA(2)-IIA, in the
      arterial wall during atherogenesis.

PMID- 11509446
TI  - Clinical imaging of the high-risk or vulnerable atherosclerotic plaque.
AB  - The study of atherosclerotic disease during its natural history and after
      therapeutic intervention will enhance our understanding of disease progression
      and regression and aid in selecting appropriate treatments. Several invasive and
      noninvasive imaging techniques are available to assess atherosclerotic vessels.
      Most of the standard techniques identify luminal diameter, stenosis, wall
      thickness, and plaque volume; however, none can characterize plaque composition
      and therefore identify the high-risk plaques. We will present the different
      imaging modalities that have been used for the direct assessment of the carotid,
      aortic, and coronary atherosclerotic plaques. We will review in detail the use of
      high-resolution, multicontrast magnetic resonance for the noninvasive imaging of
      vulnerable plaques and the characterization of plaques in terms of their various
      components (ie, lipid, fibrous, calcium, or thrombus).

PMID- 11509447
TI  - Nitric oxide synthase (NOS2) mutation in Dahl/Rapp rats decreases enzyme
      stability.
AB  - The pathogenesis of salt-sensitive hypertension remains poorly defined, but a
      role for nitric oxide (NO) has been suggested. The Dahl/Rapp salt-sensitive rat
      possesses a defect in NO synthesis that is overcome by supplementation with L
      arginine, which increases NO and cGMP production and prevents salt-sensitive
      hypertension. An S714P mutation of inducible NO synthase (NOS2) was subsequently
      identified. The current report examined the functional significance of an S714P
      mutation in NOS2. COS-7 cells were transiently transfected with cDNA of wild-type
      NOS2 and S714P and S714A mutants of NOS2, and enzyme function was determined.
      Whereas steady-state mRNA levels did not differ, immunoblot analysis demonstrated
      decreased levels of NOS2 protein. Metabolic labeling experiments confirmed a
      reduced half-life of the S714P mutation. Nitrite production, which was dependent
      on the concentration of L-arginine in the medium, was diminished in cells
      transfected with the S714P mutant, compared with the wild type and the S714A
      mutant. These data provide a biochemical explanation of the physiological
      abnormalities of NOS2 in the Dahl/Rapp salt-sensitive rat and suggest that a
      posttranslational mechanism involving the proteasome may be responsible for the
      diminished NO production observed in response to increased dietary salt intake in
      these animals.

PMID- 11509448
TI  - p27-p16 fusion gene inhibits angioplasty-induced neointimal hyperplasia and
      coronary artery occlusion.
AB  - Inhibition of proliferative neointima formed by vascular smooth muscle cells is a
      potential target in preventing angioplasty-induced restenosis. We have created a
      potent antiproliferative by fusing the active regions of the p27 and p16 cell
      cycle inhibitors. Intravascular delivery of a replication-deficient adenoviral
      vector (AV) encoding this p27-p16 fusion protein, named W9, inhibited balloon
      injury-induced neointimal hyperplasia in rabbit carotid arteries. In a
      therapeutically more relevant model, AV-W9 was delivered to balloon-injured
      porcine coronary arteries in vivo using an infusion catheter. Of the three
      coronary arteries, two were injured with a 15-mm balloon catheter and either were
      left untreated or were treated with 10(12) viral particles of either AV-W9 or a
      control null virus. AV-W9 treatment significantly inhibited neointimal
      hyperplasia in this porcine arterial balloon injury model compared with untreated
      or control virus-treated vessels. The average intimal area of the AV-W9-treated
      group 10 days after balloon injury and treatment was 0.42+/-0.36 mm(2), whereas
      the AV-null group demonstrated an intimal area of 0.70+/-0.52 mm(2). At day 10
      the average intimal thickness of the AV-W9-treated vessels was 9.1 microm (n=5, x
      20 magnification) compared with 21.2 microm (n=5, x 20 magnification) in control
      virus-treated vessels. This trend was also observed at 28 days after balloon
      injury and gene transfer during which AV-W9-treated vessels demonstrated an
      average intimal thickness of 4.7 microm (n=8, x 20 magnification) compared with
      13.3 microm (n=3, x 20 magnification) in control virus-treated vessels and 7.3
      microm (n=5, x 20 magnification) in the sham-treated vessels. The AV-W9 treatment
      was safe and well tolerated. These data suggest that AV-W9 gene therapy may be
      useful in preventing angioplasty-induced intimal hyperplasia in the coronary
      artery.

PMID- 11509449
TI  - Action potential characteristics and arrhythmogenic properties of the cardiac
      conduction system of the murine heart.
AB  - Studies have characterized conduction velocity in the right and left bundle
      branches (RBB, LBB) of normal and genetically engineered mice. However, no
      information is available on the action potential characteristics of the
      specialized conduction system (SCS). We have used microelectrode techniques to
      characterize action potential properties of the murine SCS, as well as epicardial
      and endocardial muscle preparations for comparison. In the RBB, action potential
      duration at 50%, 70%, and 90% repolarization (APD(50,70,90)) was 6+/-0.7, 35+/-6,
      and 90+/-7 ms, respectively. Maximum upstroke velocity (dV/dt(max)) was 153+/-14
      V/s, and conduction velocity averaged 0.85+/-0.2 m/s. APD(90) was longer in the
      Purkinje network of fibers (web) than in the RBB (P<0.01). Web APD(50) was longer
      in the left than in the right ventricle (P<0.05). Yet, web APD(90) was longer in
      the right than in the left ventricle (P<0.001). APD(50,70) was significantly
      longer in the endocardial than in the epicardial (P<0.001; P<0.003). APD(90) in
      the epicardial and endocardial was shorter than in the RBB ( approximately 36 ms
      versus approximately 100 ms). Spontaneous electrical oscillations in phase 2 of
      the SCS occasionally resulted in early afterdepolarizations. These results
      demonstrate that APDs in the murine SCS are significantly ( approximately 2-fold)
      longer than in the myocardium and implicate the role of the murine SCS in
      arrhythmias. The differences should have important implications in the use of the
      mouse heart to study excitation, propagation, and arrhythmias.

PMID- 11509450
TI  - A TREK-1-like potassium channel in atrial cells inhibited by beta-adrenergic
      stimulation and activated by volatile anesthetics.
AB  - Many members of the two-pore-domain potassium (K(+)) channel family have been
      detected in the mammalian heart but the endogenous correlates of these channels
      still have to be identified. We investigated whether I(KAA), a background K(+)
      current activated by negative pressure (stretch) and by arachidonic acid (AA) and
      sensitive to intracellular acidification, could be the native correlate of TREK-1
      in adult rat atrial cells. Using the inside-out configuration of the patch-clamp
      technique, we found that I(KAA), like TREK-1, was outwardly rectifying in
      physiological K(+) conditions, with a conductance of 41 pS at +50 mV. Like TREK
      1, I(KAA) was reversibly activated by clinical concentrations of volatile
      anesthetics (in mmol/L, chloroform 0.18, halothane 0.11, and isoflurane 0.69). In
      cell-attached experiments, I(KAA) was inhibited by chlorophenylthio-cAMP (500
      micromol/L) and also by stimulation of beta-adrenergic receptors with
      isoproterenol (1 micromol/L). In addition, TREK-1 mRNAs were detected in all
      cardiac tissues, and the TREK-1 protein was immunolocalized in isolated atrial
      myocytes. Such a background potassium channel might contribute to the positive
      inotropic effects produced by beta-adrenergic stimulation of the heart. It might
      also be involved in the regulation of the atrial natriuretic peptide secretion.

PMID- 11509451
TI  - Targeted alpha(1A)-adrenergic receptor overexpression induces enhanced cardiac
      contractility but not hypertrophy.
AB  - Activation of the alpha(1A)-adrenergic receptor (alpha(1A)-AR)/Gq pathway has
      been implicated as a critical trigger for the development of cardiac hypertrophy.
      However, direct evidence from in vivo studies is still lacking. To address this
      issue, transgenic mice with cardiac-targeted overexpression of the alpha(1A)-AR
      (4- to 170-fold) were generated, using the rodent alpha-myosin heavy chain
      promoter. Heterozygous animals displayed marked enhancement of cardiac
      contractility, evident from increases in dP/dt(max) (80%, P<0.0001),
      dP/dt(max)/LVP(inst) (76%, P<0.001), dP/dt(max):dP/dt(min) (104%, P<0.0001), and
      fractional shortening (33%, P<0.05). Moreover, changes in the dP/dt(max)-end
      diastolic volume relationship provided load-independent evidence of a primary
      increase in contractility. Blood pressure and heart rate were largely unchanged,
      and there was a small increase in (-)norepinephrine-stimulated, but not basal,
      phospholipase C activity. Increased contractility was directly related to the
      level of receptor overexpression and could be completely reversed by acute
      alpha(1A)- but not beta-AR blockade. Despite the robust changes in contractility,
      transgenic animals displayed no morphological, histological, or echocardiographic
      evidence of left ventricular hypertrophy. In addition, apart from an increase in
      atrial natriuretic factor mRNA, expression of other hypertrophy-associated genes
      was unchanged. To our knowledge, these data provide the first in vivo evidence
      for an inotropic action of the alpha(1A)-AR.

PMID- 11509452
TI  - Mice lacking inducible nitric oxide synthase have improved left ventricular
      contractile function and reduced apoptotic cell death late after myocardial
      infarction.
AB  - Nitric oxide produced by inducible nitric oxide synthase (NOS2) has been
      implicated in the pathophysiology of chronic myocardial remodeling and failure.
      We tested the role of NOS2 in left ventricular (LV) remodeling early (1 month)
      and late (4 months) after myocardial infarction (MI) in mice lacking NOS2. MI
      size measured 7 days, 1 month, and 4 months after MI was the same in NOS2
      knockout (KO) and wild-type (WT) mice. The LV end-diastolic pressure-volume
      relationship measured by the isovolumic Langendorff technique showed a
      progressive rightward shift from 1 to 4 months after MI in WT mice. LV developed
      pressure measured over a range of LV volumes was reduced at 1 and 4 months after
      MI in WT mice (P<0.05 and P<0.01 versus shams, respectively). In KO mice, the
      rightward shift was similar to that in WT mice at 1 and 4 months after MI, as was
      peak LV developed pressure at 1 month after MI. In contrast, at 4 months after
      MI, peak LV developed pressure in KO mice was higher than in WT mice (P<0.05
      versus WT) and similar to that in sham-operated mice. At 1 month after MI, the
      frequency of terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL)
      positive myocytes in the remote myocardium was increased to a similar extent in
      WT and KO mice. At 4 months after MI, the frequency of apoptotic myocytes was
      increased in WT mice but not in KO mice (P<0.05 versus WT). Improved contractile
      function and reduced apoptosis were associated with reduced mortality rate in KO
      mice at 4 months after MI. Thus, NOS2 does not play an important role in
      determining infarct size or early LV remodeling during the first month after MI.
      In contrast, during late (ie, 4 months after MI) remodeling, NOS2 in remote
      myocardium contributes to decreased contractile function, increased myocyte
      apoptosis in remote myocardium, and reduced survival.

PMID- 11509453
TI  - Role for endothelin-1-induced superoxide and peroxynitrite production in rebound
      pulmonary hypertension associated with inhaled nitric oxide therapy.
AB  - Our previous studies have demonstrated that inhaled nitric oxide (NO) decreases
      nitric oxide synthase (NOS) activity in vivo and that this inhibition is
      associated with rebound pulmonary hypertension upon acute withdrawal of inhaled
      NO. We have also demonstrated that inhaled NO elevates plasma endothelin-1 (ET-1)
      levels and that pretreatment with PD156707, an ETA receptor antagonist, blocks
      the rebound hypertension. The objectives of this study were to further elucidate
      the role of ET-1 in the rebound pulmonary hypertension upon acute withdrawal of
      inhaled NO. Inhaled NO (40 ppm) delivered to thirteen 4-week-old lambs decreased
      NOS activity by 36.2% in control lambs (P<0.05), whereas NOS activity was
      preserved in PD156707-treated lambs. When primary cultures of pulmonary artery
      smooth muscle cells were exposed to ET-1, superoxide production increased by 33%
      (P<0.05). This increase was blocked by a preincubation with PD156707.
      Furthermore, cotreatment of cells with ET-1 and NO increased peroxynitrite levels
      by 26% (P<0.05), whereas preincubation of purified human endothelial nitric oxide
      synthase (eNOS) protein with peroxynitrite generated a nitrated enzyme with 50%
      activity relative to control (P<0.05). Western blot analysis of peripheral lung
      extracts obtained after 24 hours of inhaled NO revealed a 90% reduction in 3
      nitrotyrosine residues (P<0.05) in PD156707-treated lambs. The nitration of eNOS
      was also reduced by 40% in PD156707-treated lambs (P<0.05). These data suggest
      that the reduction of NOS activity associated with inhaled NO therapy may involve
      ETA receptor-mediated superoxide production. ETA receptor antagonists may prevent
      rebound pulmonary hypertension by protecting endogenous eNOS activity during
      inhaled NO therapy.

PMID- 11509454
TI  - Elevated blood pressure in transgenic mice with brain-specific expression of
      human angiotensinogen driven by the glial fibrillary acidic protein promoter.
AB  - In addition to the circulatory renin (REN)-angiotensin system (RAS), a tissue RAS
      having an important role in cardiovascular function also exists in the central
      nervous system. In the brain, angiotensinogen (AGT) is expressed in astrocytes
      and in some neurons important to cardiovascular control, but its functional role
      remains undefined. We generated a transgenic mouse encoding the human AGT (hAGT)
      gene under the control of the human glial fibrillary acidic protein (GFAP)
      promoter to experimentally dissect the role of brain versus systemically derived
      AGT. This promoter targets expression of transgene products to astrocytes, the
      most abundant cell type expressing AGT in brain. All transgenic lines exhibited
      hAGT mRNA expression in brain, with variable expression in other tissues. In one
      line examined in detail, transgene expression was high in brain and low in
      tissues outside the central nervous system, and the level of plasma hAGT was not
      elevated over baseline. In the brain, hAGT protein was mainly localized in
      astrocytes, but was present in neurons in the subfornical organ.
      Intracerebroventricular (ICV) injection of human REN (hREN) in conscious
      unrestrained mice elicited a pressor response, which was abolished by ICV
      preinjection of losartan. Double-transgenic mice expressing the hREN gene and the
      GFAP-hAGT transgene exhibited a 15-mm Hg increase in blood pressure and an
      increased preference for salt. Blood pressure in the hREN/GFAP-hAGT mice was
      lowered after ICV, but not intravenous losartan. These studies suggest that AGT
      synthesis in the brain has an important role in the regulation of blood pressure
      and electrolyte balance.

PMID- 11509455
TI  - Ventricular fibrillation: Mother rotor or multiple wavelets?

PMID- 11509456
TI  - Health promotion and chronic disease: building on the Ottawa Charter, not
      betraying it?

PMID- 11509457
TI  - Promoting health knowledge through micro-credit programmes: experience of BRAC in
      Bangladesh.
AB  - This paper aims to assess the contribution of the micro-credit programme in
      raising health knowledge among poor women in rural Bangladesh. Data were
      collected from the 1998 sample survey of 500 mothers aged 15-49 years who had at
      least one child aged <5 years. Findings revealed that the socio-demographic
      factors such as the age of the woman, land ownership of the family and occupation
      of husband had no association with the prevalence of maternal knowledge. The
      knowledge was much greater among credit forum participants than non-participants,
      although exposure to the media and the education of women had also played a
      significant role in raising the level of knowledge. Multivariate analysis
      suggested that the duration of credit programme participation and exposure to the
      media were significantly more likely to raise the health knowledge among women
      when the influence of demographic and socio-economic factors were controlled. The
      paper concludes that the micro-credit programme can be an effective tool in
      promoting health among poor women in Bangladesh.

PMID- 11509458
TI  - Sustaining habits of attending cultural events and maintenance of health: a
      longitudinal study.
AB  - The purpose of this study was to assess how changes in the habit of attending
      cultural events in the community might predict self-reported health. This study
      made use of data based on two interviews, 8 years apart, with 3793 adults aged 25
      74 years from a simple random sample of the Swedish population. The subjects were
      interviewed in 1982-1983 and re-interviewed using the same questionnaire in 1990
      1991. The setting was a Swedish interview survey of living conditions comprising
      a random sample of the adult population. Self-reported health status was the main
      outcome measure. The variables used for control purposes were baseline health
      status according to the survey of 1982-1983, age (at baseline), type of
      residence, geographical region of domicile, and socio-economic status (level of
      education). A correlation was found between perceived poor health and all the
      independent variables, as well as an influence in the expected direction for all
      of them; poor education, increasing age and a low degree of urbanization all
      predicted poorer perceived health. In the full model (including all nine
      independent variables), those who became culturally less active between the first
      and second occasion, or those who were culturally inactive on both occasions, ran
      a 65% excess risk of impaired perceived health compared with those who were
      culturally active on both occasions. Furthermore, those who changed from being
      culturally less active to being more active had about the same level of perceived
      risk as those active on both occasions. These results could be in agreement with
      a causal influence of stimulation and suggest that cultural stimulation is a
      'perishable commodity'. While recruiting new consumers would in that case promote
      health, continued frequent replenishment of the cultural stimulation may be just
      as important.

PMID- 11509459
TI  - Effectiveness of a community leaders' programme to promote healthy lifestyles in
      Tokyo, Japan.
AB  - The aim of this study was to evaluate a community-based health promotion
      programme in terms of changing: (i) attitudes with respect to a healthy
      lifestyle; (ii) behaviour with respect to access to health-related information;
      and (iii) attitudes and health literacy regardless of socio-economic status. In
      this programme, 20 people are selected every 2 years in each municipality from
      the lay people of the community, and they are designated as members of a
      'community leaders' committee' by the Mayor. They, as a group, have opportunities
      to gain knowledge about and skills in healthy lifestyles, and undertake voluntary
      activities to serve the community. A programme intervention sample (INT group)
      was selected from programme participants from 13 municipalities in the greater
      Tokyo area. A questionnaire survey was carried out with the INT group and a
      general population group (REF group). The data obtained for female respondents,
      aged 30-59 years, in the two sample populations (n = 662 and 1361, respectively)
      were analysed using the chi(2) test, the Kruskal-Wallis test and multivariate log
      linear methods. Another questionnaire was given to female programme participants
      (n = 200) to identify any changes since the start of their participation. The
      results showed that the people in the INT group were pursuing healthier
      lifestyles than those in the REF group; current non-smokers who performed
      physical exercise and who ate meals regularly paid more attention to a healthy
      lifestyle and were more interested in the relationship between food and health.
      From the INT and REF groups, 22 and 4% of people, respectively, frequently
      obtained information from health professionals, and 29.8 and 10.8%, respectively,
      were satisfied with their access to health-related information. Results of
      multivariate log-linear analysis showed that significantly more people in the INT
      group were doing exercise, eating meals regularly, paying attention to
      nutritional balance and to food additives, were interested in health, and were
      satisfied with access to health information, after excluding the effects of age
      and socio-economic factors (p < 0.05). The results also showed positive changes
      after the implementation of the programme. These findings indicated that the
      people in the INT group were significantly more likely to pursue a healthier
      lifestyle and to have greater health literacy than those in the REF group,
      regardless of socio-economic status. In conclusion, this community participation
      approach, employing a committee style, was effective in improving health-related
      behaviour and in promoting health literacy while overcoming socio-economic
      variation.

PMID- 11509460
TI  - Child health-centre-based promotion of a tobacco-free environment--a Swedish case
      study.
AB  - Environmental tobacco smoke exposure is an important health risk for small
      children. The development, spread and evaluation of a national child health
      centre-based counselling method targeting environmental tobacco smoke is
      described. The work progressed in six steps. In a first step, accomplished in
      1994, it was found that child health nurses used a limited repertoire of
      techniques and were dissatisfied with their discussion on tobacco smoke. In a
      second step, routine recording of parental smoking status was introduced at all
      child health centres. In a third step, a counselling method based on Bandura's
      self-efficacy concept was developed, 'smoke-free children'. In a fourth step,
      smoke-free children was tested by 28 nurses in 128 families. At follow-up
      discussions, all parents said that they now smoked outdoors and that they had cut
      down on their smoking. In a fifth step, the national dissemination of smoke-free
      children was studied. A manual and a videotape were launched in 1995, supported
      by a newsletter and 10 regional conferences in the following years. In January
      1997, 36% of the child health nurses in Sweden (three counties excluded) stated
      that they used the method. Training of county instructors did not seem to have
      improved dissemination. In a sixth step, routinely collected information on
      parental smoking in Stockholm county on infants born 1995-1997 was used to study
      the effect. Little change in smoking rates between two consecutive years was
      found before the introduction of smoke-free children. Yet, after training of the
      child health nurses, the annual decrease was 1.7% in a pilot area and later, in
      remaining parts of the county, 2.7%. Thus, answers to two crucial questions were
      given: first, that the method seemed to affect parental behaviour; and secondly,
      that the training of county instructors might not have affected the dissemination
      of smoke-free children.

PMID- 11509461
TI  - Effectiveness of a cognitive behaviour therapy self-help programme for smokers in
      London, UK.
AB  - One of the key goals of health promotion strategies in the UK and other developed
      countries is to reduce the prevalence of cigarette consumption. While overall
      smoking rates in the UK have fallen over the last few decades, they have barely
      fallen for the least advantaged adults (Department of Health, 1998a). There is a
      need for interventions that are suitable for lower socio-economic status (SES)
      smokers that have undergone rigorous evaluation. This study describes a
      randomized controlled trial of cognitive behaviour therapy (CBT) with smokers
      from a deprived area of London. At 6 months follow-up, 21 (17.2%) of 122
      participants receiving therapy were abstinent and 14 (11.5%) had reduced
      cigarette consumption by at least 25% of pre-treatment level. Six (5.6%) of 107
      participants in the control group were abstinent and none had reduced
      consumption. These results suggest that this self-help CBT intervention has the
      potential to reduce the prevalence of smoking among lower SES smokers.

PMID- 11509462
TI  - Strengthening the evidence base for health promotion.
AB  - This paper describes the evidence debate from the many players currently
      attempting to define best practices in health promotion. Expert opinions on the
      purpose of collecting evidence range from those who view evidence as a western
      notion of little use in the developing world to those who choose to focus on
      opportunities to demonstrate the effectiveness of health promotion. There is also
      much disagreement on what constitutes evidence. Some view evidence as strict
      outcomes of randomized clinical trials (RCT) and others place greater value on
      other unpublished sources, not traditionally viewed as valuable information. A
      challenge for health promotion in the new century is to foster and develop high
      quality, widely recognized and acceptable standards for evidence-based
      evaluation.

PMID- 11509463
TI  - Promoting social responsibility for health: health impact assessment and healthy
      public policy at the community level.
AB  - The 1997 Jakarta Declaration on Health Promotion into the 21st Century called for
      new responses to address the emerging threats to health. The declaration placed a
      high priority on promoting social responsibility for health, and it identified
      equity-focused health impact assessment as a high priority for action. This theme
      was among the foci at the 2000 Fifth Global Conference on Health Promotion held
      in Mexico. This paper, which is an abbreviation of a technical report prepared
      for the Mexico conference, advances arguments for focusing on health impact
      assessment at the local level. Health impact assessment identifies negative
      health impacts that call for policy responses, and identifies and encourages
      practices and policies that promote health. Health impact assessment may be
      highly technical and require sophisticated technology and expertise. But it can
      also be a simple, highly practical process, accessible to ordinary people, and
      one that helps a community come to grips with local circumstances that need
      changing for better health. To illustrate the possibilities, this paper presents
      a case study, the People Assessing Their Health (PATH) project from Eastern Nova
      Scotia, Canada. It places ordinary citizens, rather than community elites, at the
      very heart of local decision-making. Evidence from PATH demonstrates that low
      technology health impact assessment, done by and for local people, can shift
      thinking beyond the illness problems of individuals. It can bring into
      consideration, instead, how programmes and policies support or weaken community
      health, and illuminate a community's capacity to improve local circumstances for
      better health. This stands in contrast to evidence that highly technological
      approaches to community-level health impact assessment can be self-defeating.
      Further development of simple, people-centred, low technology approaches to
      health impact assessment at the local level is called for.

PMID- 11509464
TI  - People, partnerships and human progress: building community capital.
AB  - The Victorian-era journal The Sanitarian used on its masthead the slogan 'A
      nation's health is a nation's wealth'. Today, we are re-discovering that wisdom,
      recognizing that health is indeed a form of wealth. Moreover, we are beginning to
      understand that wealth is not merely our economic capital, but includes three
      other forms of capital--social, natural and human capital. Health is one key
      element of human capital. A healthy community is one that has high levels of
      social, ecological, human and economic 'capital', the combination of which may be
      thought of as 'community capital'. The challenge for communities in the 21st
      century will be to increase all four forms of capital simultaneously. This means
      working with suitable partners in the private sector, making human development
      the central purpose of governance, and more closely integrating social,
      environmental and economic policy. Community gardens, sustainable transportation
      systems and energy conservation programmes in community housing projects are some
      of the ways in which we can build community capital.

PMID- 11509465
TI  - Health promoting hospitals: a typology of different organizational approaches to
      health promotion.
AB  - This paper draws on a review of the literature about the types of health
      promotion activities conducted by health promoting hospitals and an observation
      of how some Australian hospitals have structured the organizational arrangements
      to be more health promoting. This paper also draws on the experiences of one of
      the authors (A.J.) in managing and evaluating an organizational change process at
      a major specialist hospital in Adelaide, South Australia, that sought to re
      orientate the hospital towards placing more emphasis on health promotion. From
      these three sources, a typology of four approaches of organizational arrangement
      to health promotion is presented. These approaches are: 'doing a health promotion
      project'; 'delegating it to the role of a specific division, department or
      staff'; 'being a health promotion setting'; and 'being a health promotion setting
      and improving the health of the community'. For the re-orientation of the
      specialist hospital to occur and be sustainable, the research indicated that over
      the case study period of 1994-1998 there had to be strong organizational
      commitment to change, supported at multiple levels of the organization, and
      reflected in policy and practice change. The paper concludes that more evaluative
      research of this type will be important if the rhetoric of healthy settings is to
      become a reality.

PMID- 11509466
TI  - Health literacy: addressing the health and education divide.
AB  - Health literacy as a discrete form of literacy is becoming increasingly important
      for social, economic and health development. The positive and multiplier effects
      of education and general literacy on population health, particularly women's
      health, are well known and researched. However, a closer analysis of the current
      HIV/AIDS epidemics, especially in Africa, indicates a complex interface between
      general literacy and health literacy. While general literacy is an important
      determinant of health, it is not sufficient to address the major health
      challenges facing developing and developed societies. As a contribution to the
      health literacy forum in Health Promotion International, this paper reviews
      concepts and definitions of literacy and health literacy, and raises conceptual,
      measurement and strategic challenges. It proposes to develop a set of indicators
      to quantify health literacy using the experience gained in national literacy
      surveys around the world. A health literacy index could become an important
      composite measure of the outcome of health promotion and prevention activities,
      could document the health competence and capabilities of the population of a
      given country, community or group and relate it to a set of health, social and
      economic outcomes.

PMID- 11509468
TI  - DASH (Dietary Approaches to Stop Hypertension) diet is effective treatment for
      stage 1 isolated systolic hypertension.
AB  - Use of the DASH (Dietary Approaches to Stop Hypertension) diet, which is rich in
      fruits, vegetables, and low-fat dairy foods, significantly lowers blood pressure.
      Among the 459 participants in the DASH Trial, 72 had stage 1 isolated systolic
      hypertension (ISH) (systolic blood pressure, 140 to 159 mm Hg; diastolic blood
      pressure, <90 mm Hg). We examined the blood pressure response in these 72
      participants to determine whether the DASH diet is an effective treatment for
      stage 1 ISH. After a 3-week run-in period on a typical American (control) diet,
      participants were randomly assigned for 8 weeks to 1 of 3 diets: a continuation
      of the control diet (n=25), a diet rich in fruits and vegetables (n=24), or the
      DASH diet (n=23). Sodium content was the same in the 3 diets, and caloric intake
      was adjusted during the trial to prevent weight change. Blood pressure was
      measured at baseline and at the end of the 8-week intervention period with
      standard sphygmomanometry. Use of the DASH diet significantly lowered systolic
      blood pressure compared with the control diet (-11.2 mm Hg; 95% confidence
      interval, -6.1 to -16.2 mm Hg; P<0.001) and the fruits/vegetables diet (-8.0 mm
      Hg; 95% confidence interval, -2.5 to -13.4 mm Hg; P<0.01). Overall, blood
      pressure in the DASH group fell from 146/85 to 134/82 mm Hg. Similar results were
      observed with 24-hour ambulatory blood pressure measurements. In the DASH diet
      group, 18 of 23 participants (78%) reduced their systolic blood pressure to <140
      mm Hg, compared with 24% and 50% in the control and fruits/vegetables groups,
      respectively. Our results indicate that the DASH diet, which is rich in fruits,
      vegetables, and low-fat dairy foods, is effective as first-line therapy in stage
      1 ISH.

PMID- 11509469
TI  - Wine polyphenols decrease blood pressure, improve NO vasodilatation, and induce
      gene expression.
AB  - The effects of short-term oral administration of red wine polyphenolic compounds
      on hemodynamic parameters and on vascular reactivity were investigated in rats.
      Endothelial function and vascular smooth muscle contractility were studied in
      association with the induction of gene expression in the vascular wall. Rats were
      treated daily for 7 days by intragastric administration of either 5% glucose or
      red wine polyphenolic compounds (20 mg/kg). Administration of these compounds
      produced a progressive decrease in systolic blood pressure, which became
      significantly different on day 4. Aortas from rats treated with red wine
      polyphenolic compounds displayed increased endothelium-dependent relaxation to
      acetylcholine that was related to increased endothelial NO activity and involved
      a mechanism sensitive to superoxide anion scavengers. However, no increase in
      whole-body oxidative stress has been observed in rats treated with red wine
      polyphenolic compounds, as shown by plasma glutathione assay. Also, in the aorta,
      red wine polyphenolic compounds increased the expression of cyclooxygenase-2 and
      increased the release of endothelial thromboxane A(2), which compensated for the
      extraendothelial NO-induced hyporeactivity in response to norepinephrine,
      resulting from enhanced inducible NO synthase expression. The present study
      provides evidence that short-term oral administration of red wine polyphenolic
      compounds produces a decrease in blood pressure in normotensive rats. This
      hemodynamic effect was associated with an enhanced endothelium-dependent
      relaxation and an induction of gene expression (of inducible NO synthase and
      cyclooxygenase-2) within the arterial wall, which together maintain unchanged
      agonist-induced contractility. These effects of red wine polyphenolic compounds
      may be a potential mechanism for preventing cardiovascular diseases.

PMID- 11509470
TI  - Iron supplementation inhibits cough associated with ACE inhibitors.
AB  - Dry cough is the most common limiting factor of ACE inhibitor (ACEI) use.
      Generation of NO, a proinflammatory substance on bronchial epithelial cells, is
      increased by ACEI. Using a randomized, double-blind, placebo-controlled trial, we
      tested the hypothesis that supplementing iron, an inhibitor of NO synthase, may
      reduce the cough associated with ACEI use. The subjects were 19 patients who had
      developed ACEI-induced cough. After a 2-week observation period, they were
      randomized to a daily morning dose of either 256-mg ferrous sulfate as a tablet
      or placebo for a treatment period of 4 weeks. The subjects were requested to fill
      out a cough diary by scoring the daily severity of the cough on a scale of 0 to
      4. Mean daily cough scores for the last week of the observation and treatment
      period were compared. Changes in blood cell count and serum iron and ferritin
      concentration between the 2 periods were evaluated. Mean daily cough scores
      during the observation and treatment periods were 3.07+/-0.70 and 1.69+/-1.10,
      respectively, for the iron group and 2.57+/-0.80 and 2.35+/-1.22, respectively,
      for the placebo group, showing a significant reduction in cough scores with iron
      supplementation (P<0.01) but not with placebo. Three subjects in the iron group
      showed almost complete cough abolition. No significant changes in laboratory data
      were observed in either group. In conclusion, iron supplementation successfully
      decreases ACEI-induced cough. This effect may be related to the decrease of NO
      generation associated with the inhibition of NO synthase activity in bronchial
      epithelial cells.

PMID- 11509471
TI  - Hypertensive nephrosclerosis as a relevant cause of chronic renal failure.
AB  - It is currently unclear whether hypertensive nephrosclerosis (HN), usually
      diagnosed solely on clinical grounds, is a relevant cause of end-stage renal
      disease. We biopsied 81 hypertensive outpatients (blood pressure >/=160/95 mm Hg)
      with moderate renal insufficiency, who were referred to our service from 1988 to
      1998. Patients with known causes of hypertension, systemic disorders, rheumatic
      disease, or nephrotic syndrome were excluded. In 65% of patients, HN was the sole
      histological abnormality associated with renal dysfunction. Benign
      nephrosclerosis (BN), defined as isolated arteriolar hyalinosis and/or intimal
      fibrosis, was found in 18 HN patients (22%), whereas malignant nephrosclerosis
      (MN), denoted mainly by myointimal cell proliferation, appeared in 35 HN patients
      (43%). Previously undiagnosed primary nephritis (PN) was found in 13 patients
      (16%), whereas focal and segmental glomerulosclerosis, which might be either
      primary or secondary to hypertension, appeared in 15 patients (19%). These
      findings suggest that HN, in both its BN and MN forms, can be a definite cause of
      chronic renal insufficiency and that a substantial fraction of patients with
      renal insufficiency and clinical diagnosis of HN may actually have PN.

PMID- 11509472
TI  - Downregulation of angiotensin II type 1 receptors during sepsis.
AB  - Our study aimed to characterize the mechanisms underlying the attenuated
      cardiovascular responsiveness toward the renin-angiotensin system during sepsis.
      For this purpose, we determined the effects of experimental Gram-negative and
      Gram-positive sepsis in rats. We found that sepsis led to a ubiquitous
      upregulation of NO synthase isoform II expression and to pronounced hypotension.
      Despite increased plasma renin activity and plasma angiotensin (Ang) II levels,
      plasma aldosterone concentrations were normal, and the blood pressure response to
      exogenous Ang II was markedly diminished in septic rats. Mimicking the fall of
      blood pressure during sepsis by short-term infusion of the NO donor sodium
      nitroprusside in normal rats did not alter their blood pressure response to
      exogenous Ang II. Therefore, we considered the possibility of an altered
      expression of Ang II receptors during sepsis. It turned out that Ang II type 1
      receptor expression was markedly downregulated in all organs of septic rats.
      Further in vitro studies with rat renal mesangial cells showed that NO and a
      combination of proinflammatory cytokines (interleukin-1beta, tumor necrosis
      factor-alpha, and interferon-gamma) downregulated Ang II type 1 receptor
      expression in a synergistic fashion. In summary, our data suggest that sepsis
      causes a systemic downregulation of Ang II type 1 receptors that is likely
      mediated by proinflammatory cytokines and NO. We suggest that this downregulation
      of Ang II type 1 receptors is the main reason for the attenuated responsiveness
      of blood pressure and of aldosterone formation to Ang II and, therefore,
      contributes to the characteristic septic shock.

PMID- 11509473
TI  - Angiotensin-converting enzyme inhibition potentiates angiotensin II type 1
      receptor effects on renal bradykinin and cGMP.
AB  - Angiotensin (Ang) receptor blockers (ARBs) increase bradykinin (BK) by
      antagonizing Ang II at its type 1 (AT(1)) receptors and diverting Ang II to its
      counterregulatory type 2 (AT(2)) receptors. Because the effect of ARBs on BK is
      constrained by the short half-life of BK and because ACE inhibitors block the
      degradation of BK, this study was designed to test the hypothesis that an ACE
      inhibitor can potentiate ARB-induced increases in renal interstitial fluid (RIF)
      BK levels. We used a microdialysis technique to recover BK and cGMP in vivo from
      the RIF of sodium-depleted, conscious Sprague-Dawley rats infused for 60 minutes
      with the AT(1) receptor blocker valsartan (0.17 mg/kg per minute), with the
      active metabolite of the ACE inhibitor benazepril (benazeprilate, 0.05 mg/kg per
      minute), or with the specific AT(2) receptor blocker PD 123,319 (50 microg/kg per
      minute) alone or combined. Each animal served as its own control. RIF BK and cGMP
      levels increased significantly over 1 hour in response to valsartan,
      benazeprilate, or both but not to a vehicle control (P<0.01). The combined
      benazeprilate-valsartan effect was greater than the sum of their individual
      effects, suggesting potentiation rather than addition, and was abolished by PD
      123,319. We demonstrate for the first time that an ACE inhibitor (benazepril) and
      an ARB (valsartan) potentiate each other, and we postulate that such combinations
      may be beneficial in clinical states marked by Ang II elevation, such as chronic
      heart failure, postinfarction left ventricular dysfunction, and hypertension.

PMID- 11509474
TI  - Endogenous natriuretic peptides participate in renal and humoral actions of acute
      vasopeptidase inhibition in experimental mild heart failure.
AB  - Mild heart failure is characterized by increases in atrial natriuretic peptide
      (ANP) and brain natriuretic peptide (BNP) in the absence of activation of the
      renin-angiotensin-aldosterone system (RAAS). Vasopeptidase (VP) inhibitors are
      novel molecules that coinhibit neutral endopeptidase 24.11, which degrades the
      natriuretic peptides (NPs) and ACE. In a well-characterized canine model of mild
      heart failure produced by ventricular pacing at 180 bpm for 10 days, we defined
      the renal and humoral actions of acute VP inhibition with omapatrilat (OMA, n=6)
      and acute ACE inhibition (n=5) alone with fosinoprilat. We also sought to
      determine whether the NPs participate in the renal actions of acute VP inhibition
      by the administration of OMA together with an intrarenal administration of the NP
      receptor antagonist HS-142-1 (n=5). OMA resulted in a greater natriuretic
      response than did ACE inhibition in association with increases in plasma cGMP,
      ANP, BNP, urinary cGMP, urinary ANP excretion, and glomerular filtration rate
      (P<0.05 for OMA versus ACE inhibition). Plasma renin activity was increased only
      in the group subjected to ACE inhibition. Administration of intrarenal HS-142-1
      attenuated the renal properties of OMA in association with a decrease in urinary
      cGMP excretion despite similar increases in plasma ANP and BNP. This study
      provides new insight into a unique new pharmacological agent that has beneficial
      renal actions in experimental mild heart failure beyond the actions that are
      observed with ACE inhibition alone and that are linked to the NP system.

PMID- 11509475
TI  - Effect of dietary sodium intake on the responses to bicuculline in the
      paraventricular nucleus of rats.
AB  - The tachycardic, pressor, and renal sympathoexcitatory responses produced by
      administration of the gamma-aminobutyric acid antagonist bicuculline into the
      paraventricular nucleus of the rat are attenuated by the administration of
      losartan, an angiotensin II type 1 receptor antagonist, into the ipsilateral
      rostroventrolateral medulla. Therefore, excitatory synaptic inputs to pressor
      neurons in the rostroventrolateral medulla that arise from activation of the
      paraventricular nucleus are mediated predominantly by the action of angiotensin
      II on angiotensin II type 1 receptors. To examine whether such responses are
      influenced by physiological changes in the activity of the renin-angiotensin
      system, we measured heart rate, arterial pressure, and renal sympathetic nerve
      activity responses to the administration of bicuculline in the paraventricular
      nucleus in normal rats that were fed low-, normal-, and high-sodium diets and in
      rats with congestive heart failure. The rank order of both plasma renin activity
      and renal sympathoexcitatory responses was congestive heart failure>low-sodium
      diet>normal-sodium diet>high-sodium diet. The rank order of pressor and
      tachycardic responses exhibited a similar trend, but the differences between the
      groups were smaller and not statistically significant. The results indicate that
      the renal sympathoexcitatory responses to activation of the paraventricular
      nucleus are modulated by physiological alterations in the activity of the renin
      angiotensin system.

PMID- 11509476
TI  - Plasma ouabain-like factor during acute and chronic changes in sodium balance in
      essential hypertension.
AB  - An ouabain-like factor has been implicated repeatedly in salt-sensitive
      hypertension as a natriuretic agent. However, the response of plasma ouabain-like
      factor to acute and chronic variation of body sodium is unclear. We studied 138
      patients with essential hypertension who underwent an acute volume
      expansion/contraction maneuver (2 days) and 20 patients who entered a blind
      randomized crossover design involving chronically controlled sodium intake and
      depletion (170 to 70 mmol/d; 2 weeks each period). In both studies, plasma levels
      of ouabain-like factor were higher during sodium depletion (acute: 338.8+/-17.4
      and 402.7+/-22.8 pmol/L for baseline and low sodium, respectively, P<0.01;
      chronic: 320.4+/-32.0 versus 481.0+/-48.1 pmol/L, P=0.01). No significant change
      in plasma ouabain-like factor was observed after a 2-hour saline infusion
      (333.4+/-23.9 pmol/L) or controlled sodium (402.1+/-34.9 pmol/L). When patients
      were divided into salt-sensitive or salt-resistant groups, no differences in
      plasma ouabain-like factor were observed in the 2 groups at baseline or in
      response to the 2 protocols: salt resistant (n=69, 340.1+/-25.9 pmol/L) versus
      salt sensitive (n=69, 337.4+/-23.6 pmol/L) and chronic salt resistant (n=11,
      336.0+/-53.2) versus salt sensitive (n=9, 301.1+/-331.4 pmol/L). However,
      circulating ouabain-like factor was increased by sodium depletion in both groups.
      These results demonstrate that circulating ouabain-like factor is raised
      specifically by maneuvers that promote the loss of body sodium. Acute expansion
      of body fluids with isotonic saline is not a stimulus to plasma ouabain-like
      factor. Moreover, basal levels of plasma ouabain-like factor do not differ among
      patients with salt-sensitive or salt-resistant hypertension. Taken together,
      these new results suggest that ouabain-like factor is involved in the adaptation
      of humans to sodium depletion and argue against the hypothesis that ouabain-like
      factor is a natriuretic hormone.

PMID- 11509477
TI  - Interaction of alpha(1)-Na,K-ATPase and Na,K,2Cl-cotransporter genes in human
      essential hypertension.
AB  - Essential hypertension is a common disease the genetic determinants of which have
      been difficult to unravel because of its clinical heterogeneity and complex,
      multifactorial, polygenic etiology. Based on our observations that alpha(1)-Na,K
      ATPase (ATP1A1) and renal-specific, bumetanide-sensitive Na,K,2Cl-cotransporter
      (NKCC2) genes interactively increase susceptibility to hypertension in the Dahl
      salt-sensitive hypertensive (Dahl S) rat model, we investigated whether parallel
      molecular genetic mechanisms might exist in human essential hypertension in a
      relatively genetic homogeneous cohort in northern Sardinia. Putative ATP1A1-NKCC2
      gene interaction was tested by comparing hypertensive patients (blood pressure
      [BP] >165/95 mm Hg) with normotensive controls age >60 years with BP <140/85 mm
      Hg. Genotype analysis with microsatellite markers revealed conformation to Hardy
      Weinberg proportions for 6 alleles of both ATP1A1 (D1S453) and NKCC2 (NKCGT7)
      markers, respectively. Two-by-six chi(2) analysis of alleles identified
      overrepresentation of ATP1A1 No. 4 and NKCC2 No. 4 alleles, respectively, in
      hypertensives compared with controls. With a qualitative trait framework, single
      gene analysis detected association of both the ATP1A1 No. 4 allele (P=0.004,
      chi(2)=8.094, df=1) and the NKCC2 No. 4 allele (P=0.0002, chi(2)=14.279, df=1)
      with moderate to severe hypertension. Digenic analysis revealed that ATP1A1 No. 4
      NKCC2 No. 4 allele interaction increases susceptibility to hypertension
      (P<0.0001, chi(2)=22.3, df=1) beyond levels obtained in single-gene analysis.
      Analysis was also performed in a quantitative trait framework with BP as the
      continuous trait parameter. Digenic analysis of ATP1A1 No. 4-NKCC2 No. 4 allele
      interaction revealed significant association with systolic (1-way ANOVA,
      P=0.000076) and diastolic (P=0.00099) BP. Interaction was corroborated by 2x2
      factorial ANOVA for interaction (systolic BP interaction term, P<0.05, diastolic
      BP interaction term, P=0.035). The data are compelling that ATP1A1 and NKCC2
      genes are candidate interacting hypertension-susceptibility loci in human
      essential hypertension and affirm gene interaction as an important genetic
      mechanism underlying hypertension susceptibility. Although corroboration in other
      cohorts and identification of functionally significant mutations are imperative
      next steps, the data provide a genotype-stratification scheme, with 4-fold
      predictive value (odds ratio, 4.28; 95% confidence interval, 2.29 to 8.0), which
      could help decipher the complex genetics of essential hypertension.

PMID- 11509478
TI  - Human heme oxygenase-1 gene transfer lowers blood pressure and promotes growth in
      spontaneously hypertensive rats.
AB  - Heme oxygenase (HO) catalyzes the conversion of heme to biliverdin, with release
      of free iron and carbon monoxide. Both heme and carbon monoxide have been
      implicated in the regulation of vascular tone. A retroviral vector containing
      human HO-1 cDNA (LSN-HHO-1) was constructed and subjected to purification and
      concentration of the viral particles to achieve 5x10(9) to 1x10(10) colony
      forming units per milliliter. The ability of concentrated infectious viral
      particles to express human HO-1 (HHO-1) in vivo was tested. A single intracardiac
      injection of the concentrated infectious viral particles (expressing HHO-1) to 5
      day-old spontaneously hypertensive rats resulted in functional expression of the
      HHO-1 gene and attenuation of the development of hypertension. Rats expressing
      HHO-1 showed a significant decrease in urinary excretion of a vasoconstrictor
      arachidonic acid metabolite and a reduction in myogenic responses to increased
      intraluminal pressure in isolated arterioles. Unexpectedly, HHO-1 chimeric rats
      showed a simultaneous significant proportionate increase in somatic growth. Thus,
      delivery of HHO-1 gene by retroviral vector attenuates the development of
      hypertension and promotes body growth in spontaneously hypertensive rats.

PMID- 11509479
TI  - Genetic dissection of region around the Sa gene on rat chromosome 1: evidence for
      multiple loci affecting blood pressure.
AB  - A region with a major effect on blood pressure (BP) is located on rat chromosome
      1 in the vicinity of the Sa gene, a candidate gene for BP regulation. Previously,
      we observed a single linkage peak for BP in this region in second filial
      generation rats derived from a cross of the spontaneously hypertensive rat (SHR)
      with the Wistar-Kyoto rat (WKY), and we have reported the isolation of the region
      containing the BP effect in reciprocal congenic strains (WKY.SHR-Sa) and (SHR.WKY
      Sa) derived from these animals. Here, we report the further genetic dissection of
      this region. Two congenic substrains each were derived from WKY.SHR-Sa (WISA1 and
      WISA2) and SHR.WKY-Sa (SISA1 and SISA2) by backcrossing to WKY and SHR,
      respectively. Although there was some overlap of the introgressed regions
      retained in the various substrains, the segments in WISA1 and SISA1 did not
      overlap. Furthermore, although the Sa allele in WISA1, WISA2, and SISA2 remained
      donor in origin, recombination in SISA1 reverted it back to the recipient (SHR)
      allele. Surprisingly, all 4 substrains demonstrated a highly significant BP
      difference compared with that of their respective parental strain, which was of a
      magnitude similar to those seen in the original congenic strains. The findings
      strongly indicate that there are at least 2 quantitative trait loci (QTLs)
      affecting BP in this region of rat chromosome 1. Furthermore, the BP effect seen
      in SISA1 indicates that at least a proportion of the BP effect of this region of
      rat chromosome 1 cannot be due to the Sa gene. SISA1 contains an introgressed
      segment of <3 cM, and this will facilitate the physical mapping of the BP QTL(s)
      located within it and the identification of the susceptibility-conferring genes.
      Our observations serve to illustrate the complexity of QTL dissection and the
      care needed to interpret findings from congenic studies.

PMID- 11509480
TI  - Aerobic exercise training does not modify large-artery compliance in isolated
      systolic hypertension.
AB  - The present study characterized large-artery properties in patients with isolated
      systolic hypertension (ISH) and determined the efficacy of exercise training in
      modifying these properties. Twenty patients (10 male and 10 female) with stage I
      ISH and 20 age- and gender-matched control subjects were recruited, and large
      artery properties were assessed noninvasively. Ten ISH patients (5 male and 5
      female) were enrolled in a randomized crossover study comparing 8 weeks of
      moderate intensity cycling with 8 weeks of sedentary activity. Brachial and
      carotid systolic, diastolic, mean, and pulse pressures were higher in the ISH
      group than in the control group. Systemic arterial compliance (0.43+/-0.04 versus
      0.29+/-0.02 arbitrary compliance units for the control versus ISH groups,
      respectively; P=0.01) was lower, and carotid-to-femoral pulse-wave velocity
      (9.67+/-0.36 versus 11.43+/-0.51 m. s(-1) for the control versus ISH groups,
      respectively; P=0.007), input impedance (2.39+/-0.19 versus 3.27+/-0.34 mm Hg. s.
      cm(-1) for the control versus ISH groups, respectively; P=0.04), and
      characteristic impedance (1.67+/-0.17 versus 2.34+/-0.27 mm Hg. s. cm(-1) for the
      control versus ISH groups, respectively; P=0.05) were higher in the ISH group
      than in the control group. Training increased maximal oxygen consumption by 13+/
      5% (P=0.04) and maximum workload by 8+/-4% (P=0.05); however, there was no effect
      on arterial mechanical properties, blood lipids, or left ventricular mass or
      function. These results suggest that the large-artery stiffening associated with
      ISH is resistant to modification through short-term aerobic training.

PMID- 11509481
TI  - Acute effect of caffeine on arterial stiffness and aortic pressure waveform.
AB  - Caffeine acutely increases blood pressure and peripheral vascular resistance, in
      part because of sympathetic stimulation. Its effects on large artery properties
      are largely unknown. In a double-blind crossover study, 7 healthy subjects 26+/
      2.6 years of age (mean+/-SEM) were studied for 90 minutes while in the supine
      position on 2 occasions separated by a week in random order after ingestion of
      250 mL caffeinated (150 mg) and decaffeinated (<2 mg) coffee. Compared with
      baseline, arterial stiffness measured by carotid femoral pulse wave velocity
      increased progressively from 7.2+/-0.41 to 8.0+/-0.6 m/s (P<0.05) at 90 minutes
      after caffeine intake, an effect that may be independent of changes in blood
      pressure. In addition, arterial wave reflection, measured by applanation
      tonometry from the aortic pressure waveform, also increased from -5.7+/-7.6% to
      5.28%+/-5.6 (P<0.01). No such changes were seen with decaffeinated coffee intake.
      Although the integral of the brachial systolic and diastolic blood pressure
      values over the 90 minutes was larger (P<0.05) after caffeinated than
      decaffeinated coffee intake, the effect on aortic systolic and diastolic blood
      pressures was more pronounced (P<0.05) than on the brachial artery. These results
      show a significant effect of caffeine intake on arterial tone and function and
      suggest that caffeine acutely increases arterial stiffness.

PMID- 11509482
TI  - Pulse pressure compared with other blood pressure indexes in the prediction of 25
      year cardiovascular and all-cause mortality rates: The Chicago Heart Association
      Detection Project in Industry Study.
AB  - We compared the relations of 4 blood pressure (BP) indexes (pulse pressure [PP],
      systolic BP [SBP], diastolic BP [DBP], and mean arterial pressure [MAP]) with 25
      year mortality rates for coronary heart disease (CHD), cardiovascular disease
      (CVD), and all causes in younger, middle-aged, and older men and women by using
      data from a long-term prospective epidemiological study of employed persons who
      were screened between 1967 and 1973. A single supine BP measurement was obtained
      at baseline. Vital status was determined through 1995. We report on 5 groups
      (total, 28 360 participants) consisting of men age 18 to 39, 40 to 59, and 60 to
      74 years and of women age 40 to 59 and 60 to 74 years who were not receiving
      antihypertensive treatment, had no history of CHD, and did not have diabetes. Cox
      proportional hazards analyses were used to determine multivariate-adjusted hazard
      ratios with a 1-SD higher value for each BP index; Wald chi(2) tests were used to
      compare the strength of relations. Relations of PP were less strong than were
      those of SBP for all end points in all age/gender groups. SBP or MAP showed the
      strongest relations to all end points in all age/gender groups (hazard ratio,
      1.17 to 1.36). The relations of SBP to death were stronger than were those of
      DBP, except for middle-aged men and for CVD in women. DBP showed significant
      positive associations with death, after control for SBP, in middle-aged
      participants. In conclusion, these data indicate that the long-term risk of high
      BP should be assessed mainly on the basis of SBP or of SBP and DBP together, not
      on the basis of PP, in apparently healthy adults.

PMID- 11509483
TI  - Impaired skin capillary recruitment in essential hypertension is caused by both
      functional and structural capillary rarefaction.
AB  - Capillary rarefaction occurs in many tissues in patients with essential
      hypertension and may contribute to an increased vascular resistance and impaired
      muscle metabolism. Rarefaction may be caused by a structural (anatomic) absence
      of capillaries, functional nonperfusion, or both. The aim of this study was to
      assess the extent of structural versus functional capillary rarefaction in the
      skin of subjects with essential hypertension. We examined skin capillary density
      with video microscopy before and during maximization of the number of perfused
      capillaries by venous congestion (structural capillary number) and before and
      during postocclusive reactive hyperemia (capillary recruitment, which may have a
      structural and/or functional basis). The study group was composed of 26 patients
      with never-treated essential hypertension and 26 normotensive control subjects.
      In both groups, intermittently perfused capillaries in the resting state were an
      important functional reserve for recruitment during postocclusive hyperemia.
      Recruitment of perfused capillaries during postocclusive reactive hyperemia was
      decreased in the hypertensive subjects compared with normotensive control
      subjects (47.9+/-6.8 versus 55.3+/-8.2 capillaries/mm(2), respectively; P<0.01).
      During venous occlusion, maximal capillary density was significantly lower in the
      hypertensive subjects than in the control subjects (52.5+/-6.6 versus 57.2+/-8.6
      capillaries/mm(2), respectively; P<0.05), suggesting structural rarefaction.
      However, in the hypertensive subjects compared with the normotensive subjects, a
      smaller proportion of the maximal number of capillaries was perfused during
      postocclusive hyperemia (91.6+/-7.5% versus 97.2+/-2.7%, respectively; P<0.05),
      suggesting an additional functional impairment of capillary recruitment. If the
      difference in capillary numbers during venous congestion ( approximately 4.6
      capillaries/mm(2)) truly reflects the structural difference between the
      normotensive and hypertensive subjects, then, at most, 62% (4.6/7.4x100%) of the
      difference in capillary numbers during postocclusive hyperemia ( approximately
      7.4 capillaries/mm(2)) can be explained by structural defects, and at least 38%
      can be explained by functional defects. In conclusion, in patients with essential
      hypertension, recruitment of perfused capillaries is impaired, which can be
      explained by both functional and structural rarefaction.

PMID- 11509484
TI  - Renin uptake by the endothelium mediates vascular angiotensin formation.
AB  - We investigated the role of the vascular endothelium in the local production of
      angiotensin. Angiotensin release from isolated rat hindquarters perfused with an
      artificial medium was measured by high-performance liquid chromatography and
      radioimmunoassay. Perfused hindquarters with endothelium released angiotensin I
      spontaneously, indicating ongoing renin-angiotensinogen reaction. Endothelium
      denudation (by a detergent, validated by electron microscopy and by the absence
      of a vasodilator response to acetylcholine) reduced angiotensin I release by
      >90%, whereas bilateral nephrectomy 24 hours before perfusion abolished the
      release completely. Infusion of renin into perfused hindquarters induced
      sustained local angiotensin I release in the presence of an intact endothelium
      but not after endothelium denudation. The conversion of angiotensin I to
      angiotensin II was abrogated by endothelium denudation, whereas the disappearance
      of angiotensin II was unchanged. Endothelium denudation diminished the pressor
      response to angiotensin II but abolished the response to renin and angiotensin I.
      Expression of renin messenger RNA, investigated by reverse-transcription
      polymerase chain reaction using 4 different primer combinations, was not detected
      in up to 5 microg vascular RNA, whereas a renin signal was readily detected with
      5 ng kidney RNA. The effects of endothelium destruction on Ang I formation
      support the notion that the endothelium mediates vascular angiotensin formation
      by taking up renin.

PMID- 11509485
TI  - Increased expression of peroxisome proliferator-activated receptor-alpha and 
      gamma in blood vessels of spontaneously hypertensive rats.
AB  - Peroxisome proliferator-activated receptors (PPARs) are a family of ligand
      activated transcription factors that include PPAR-alpha, PPAR-gamma, and PPAR
      delta. We hypothesized that PPAR expression in blood vessels could be reduced in
      hypertension to result in increased vascular growth and reduced apoptosis. We
      investigated the abundance of PPAR-alpha and PPAR-gamma in aorta and mesenteric
      arteries from young (6-week-old) and adult (16-week-old) spontaneously
      hypertensive rats (SHR) compared with age-matched control Wistar-Kyoto rats
      (WKY). mRNA levels of PPAR-alpha and PPAR-gamma were determined by reverse
      transcription-polymerase chain reaction. Protein expression was evaluated by
      Western blot and by immunohistochemistry. PPAR-gamma was expressed in aortic and
      mesenteric vascular smooth muscle cells (VSMCs) from intact tissue and cultured
      cells. PPAR-alpha was expressed in intact vascular tissue but was almost
      undetectable in cultured VSMCs. In mesenteric arteries from adult SHR, PPAR-alpha
      and PPAR-gamma mRNA levels were significantly greater than in WKY (P<0.05). In
      aorta, PPAR-alpha mRNA was significantly (P<0.05) more abundant in adult (but not
      in young) SHR than in WKY, whereas there was no difference in PPAR-gamma mRNA
      between WKY and SHR. PPAR-alpha and PPAR-gamma mRNA were greater in mesenteric
      arteries (P<0.05) in young and adult SHR than in WKY. Expression of PPAR-alpha
      and PPAR-gamma was similar in SHR and WKY in other tissues. In cultured
      mesenteric VSMCs, PPAR-gamma mRNA was 3-fold higher in SHR than in WKY.
      Immunohistochemistry demonstrated that PPAR-gamma resided constitutively in the
      cytoplasm in primary and low-passaged aortic and mesenteric VSMCs, whereas PPAR
      alpha was almost undetectable. Thus, aorta and mesenteric resistance arteries
      from SHR in the prehypertensive and the established phase of hypertension exhibit
      increased expression of both PPAR isoforms, whereas other tissues do not. Changes
      (increases) in PPAR expression may play a compensatory role in the remodeling of
      blood vessels in SHR.

PMID- 11509486
TI  - Cardiac betaARK1 upregulation induced by chronic salt deprivation in rats.
AB  - The beta-adrenergic receptor (betaAR) kinase (betaARK1) is a G protein-coupled
      receptor kinase (GRK) that controls cardiac betaAR signaling via receptor
      phosphorylation, leading to desensitization. We have observed in mice that
      chronic isoproterenol administration results in increased myocardial levels of
      betaARK1 activity, suggesting that adrenergic activation can regulate cardiac
      betaARK1 expression. Thus, we evaluated left ventricular (LV) betaARK1 levels and
      activity in response to 3 weeks of a low-sodium (0.05%) diet, which is known to
      chronically activate the sympathetic nervous system. Wistar-Kyoto rats were
      subjected to either low or regular sodium (2%) intake. To prove the association
      of betaARK1 expression and low sodium-induced adrenergic activation, a group of
      rats was subjected to atenolol treatment (1 mg/kg per day) during the low-sodium
      diet. LV betaARK1 expression was assessed by protein immunoblotting and betaARK1
      activity by in vitro GRK phosphorylation assays. We verified the LV protein
      levels of GRK5, which is abundantly expressed in the heart. A low-sodium diet
      reduced body weight and cardiac size so that the heart-to-body weight ratio did
      not change. On the contrary, low-sodium diet increased by 50% both LV betaARK1
      protein (densitometry units: normal sodium, 26.5+/-0.9; low sodium, 35.7+/-1.6;
      P<0.05) and activity (fmol/mg per minute: normal sodium, 6.49+/-1.17; low sodium,
      9.15+/-0.93; P<0.05). Atenolol treatment prevented the increase in both protein
      expression (low sodium plus atenolol, 27.6+/-5.33, P=NS versus normal sodium) and
      activity (6.54+/-1.19, P=NS versus normal sodium). GRK5 expression was not
      affected by a low-sodium diet (17.2+/-0.2 versus 18.4+/-0.4, P=NS). Our data
      indicate that cardiac betaARK1 is regulated by sympathetic action on betaARs as
      tested by reducing dietary salt and betaAR blockade.

PMID- 11509487
TI  - Nitric oxide attenuates the expression of transforming growth factor-beta(3) mRNA
      in rat cardiac fibroblasts via destabilization.
AB  - Transforming growth factor-beta (TGF-beta) has been implicated in the development
      of interstitial fibrosis in cardiac hypertrophy. NO has been regarded as a potent
      inhibitor of cardiac fibroblast growth, albeit the modulation of cellular events
      associated with interstitial fibrosis remains undefined. In this regard, the
      regulation of TGF-beta mRNA expression by the NO donor S-nitroso-N-acetyl
      penicillamine (SNAP) was examined in neonatal rat cardiac fibroblasts. SNAP
      treatment for 4 hours decreased TGF-beta(3) mRNA levels, an effect mimicked by 8
      bromo-cGMP. TGF-beta(3) mRNA, however, had returned to levels observed in the
      untreated cells after a 24-hour exposure to SNAP, whereas a decreased expression
      persisted with 8-bromo-cGMP. In contrast to TGF-beta(3), TGF-beta(1) mRNA levels
      were modestly increased in response to cGMP-generating molecules. The treatment
      with actinomycin D for at least 8 hours did not appreciably alter TGF-beta(3)
      mRNA levels. By contrast, SNAP treatment caused a rapid decrease of TGF-beta(3)
      mRNA with a half-life of 3.3+/-0.2 hours, thereby supporting a mechanism of
      destabilization. The pretreatment with SNAP inhibited angiotensin II-stimulated
      protein synthesis and the concomitant expression of TGF-beta(3) mRNA. These data
      reveal a disparate pattern of TGF-beta(1) and TGF-beta(3) mRNA regulation by NO
      and highlight a novel mechanism of destabilization contributing to the decreased
      expression of TGF-beta(3) mRNA. The modulation of both basal and angiotensin II
      stimulated TGF-beta(3) mRNA expression provides a mechanism by which NO may
      influence the progression of interstitial fibrosis.

PMID- 11509488
TI  - Divergent biological actions of coronary endothelial nitric oxide during
      progression of cardiac hypertrophy.
AB  - Coronary endothelial NO synthase expression and NO bioactivity were investigated
      at sequential stages during the progression of left ventricular hypertrophy. Male
      guinea pigs underwent abdominal aortic banding or sham operation. Left
      ventricular contractile function was quantified in isolated ejecting hearts.
      Coronary endothelial and vasodilator function were assessed in isolated
      isovolumic hearts in response to boluses of bradykinin (0.001 to 10 micromol/L),
      substance P (0.01 to 100 micromol/L), diethylamine NONOate (DEA-NO) (0.1 to 1000
      micromol/L), N(G)-monomethyl-L-arginine monoacetate (L-NMMA) (10 mmol/L), and
      adenosine (10 mmol/L). At a stage of compensated left ventricular hypertrophy (3
      weeks), left ventricular endothelial NO synthase protein expression was unaltered
      (Western blot and immunocytochemistry). Vasoconstriction in response to L-NMMA
      was increased in banded animals compared with sham-operated animals (13.8+/-2.1%
      versus 6.2+/-1.3%, n=10; P<0.05), but agonist- and DEA-NO-induced vasodilation
      was similar in the 2 groups. At a stage of decompensated left ventricular
      hypertrophy (8 to 10 weeks), left ventricular endothelial NO synthase protein
      expression was significantly lower in banded animals (on Western analysis: banded
      animals, 7.8+/-0.4 densitometric units; sham-operated animals, 12.2+/-1.7
      densitometric units; n=5; P<0.05). At this time point, vasoconstriction in
      response to L-NMMA was similar in the 2 groups, but vasodilatation in response to
      bradykinin (30.9+/-2.4% versus 39.7+/-2.2%, n=10; P<0.05), DEA-NO (26.2+/-1.8%
      versus 34.6+/-1.8%, n=10; P<0.05), and adenosine (24.3+/-2.0% versus 35.7+/-2.0%,
      n=10; P<0.01) was attenuated in banded animals. These findings indicate that
      there is an increase in the basal activity of NO (without a significant change in
      endothelial NO synthase expression) in early compensated left ventricular
      hypertrophy, followed by a decrease in both endothelial NO synthase expression
      and NO bioactivity during the transition to myocardial failure.

PMID- 11509489
TI  - Age-related reduction of NO availability and oxidative stress in humans.
AB  - Age-related endothelial dysfunction could be caused by an alteration in the L
      arginine-NO system and the production of oxidative stress in both normotensive
      and hypertensive individuals. In 47 normotensive subjects and 49 patients with
      essential hypertension, we evaluated forearm blood flow (by strain-gauge
      plethysmography) modifications induced by intrabrachial sodium nitroprusside (1,
      2, and 4 microg/100 mL per minute) and acetylcholine (0.15, 0.45, 1.5, 4.5, and
      15 microg/100 mL per minute), an endothelium-independent vasodilator and an
      endothelium-dependent vasodilator, respectively. Acetylcholine was repeated in
      the presence of the NO synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA, 100
      microg/100 mL per minute), the antioxidant vitamin C (8 mg/100 mL per minute), or
      both. Vasodilation to acetylcholine, but not to sodium nitroprusside, was lower
      (P<0.01) in hypertensive patients compared with control subjects. Moreover, in
      both groups, endothelium-dependent vasodilation declined with aging. In
      normotensive subjects, the inhibiting effect of L-NMMA on response to
      acetylcholine decreased in parallel with advancing age, whereas vitamin C
      increased vasodilation to acetylcholine in only the oldest group (age >60 years).
      In young hypertensive patients (age <30 years), vasodilation to acetylcholine was
      sensitive to L-NMMA, whereas in hypertensive patients age >30 years, vitamin C
      enhanced endothelium-dependent vasodilation and restored the inhibiting effect of
      L-NMMA on response to acetylcholine. In normotensive individuals, an earlier
      primary dysfunction of the NO system and a later production of oxidative stress
      cause age-related reduction in endothelium-dependent vasodilation. These
      alterations are similar but anticipated in hypertensive patients compared with
      normotensive subjects.

PMID- 11509490
TI  - Role of nNOS in regulation of renal function in angiotensin II-induced
      hypertension.
AB  - Previous studies have indicated that in normotensive rats, NO produced by
      neuronal NO synthase (nNOS) plays an important role in modulating
      tubuloglomerular feedback (TGF)-mediated afferent arteriolar constriction. It has
      also been shown that in angiotensin (Ang) II-infused hypertensive rats, there is
      a reduced ability of nNOS-derived NO to counteract this vasoconstriction. The
      present study was performed to (1) assess in vivo renal functional responses to
      intrarenal nNOS inhibition in control and Ang II-infused rats and (2) determine
      whether changes in renal function following nNOS inhibition are mediated by
      unopposed stimulation of Ang II receptor subtype 1 (AT(1)). Wistar rats were
      infused with either saline (SAL) or Ang II (80 ng/min) by osmotic minipumps
      implanted subcutaneously. Mean arterial blood pressure of SAL- and Ang II-infused
      rats on day 13 after implantation averaged 121+/-4 (n=28) and 151+/-5 (n=30),
      respectively (P<0.05). There were no differences in glomerular filtration rate
      (GFR) (0.68+/-0.09 versus 0.59+/-0.09 mL. min(-1). g(-1)), renal plasma flow
      (RPF) (2.66+/-0.31 versus 2.34+/-0.39 mL. min(-1). g(-1)), and absolute sodium
      excretion (0.37+/-0.07 versus 0.42+/-0.09 micromol. min(-1). g(-1)). Intrarenal
      infusion of SAL did not change GFR, RPF, and sodium excretion in either SAL
      infused (n=7) or Ang II-infused rats (n=8). Acute intrarenal administration of
      the nNOS inhibitor S-methyl-L-thiocitrulline (L-SMTC; 0.3 mg/h) decreased GFR,
      RPF, and sodium excretion in SAL-infused rats (n=9) by 29+/-4%, 38+/-4%, and 70+/
      4% compared with control values (P<0.05). The pretreatment by the AT(1) receptor
      antagonist candesartan (750 ng IR) in SAL-infused rats (n=7) effectively
      prevented the decrease in RPF (-3+/-3%) elicited by nNOS inhibition and resulted
      in an increase in GFR (+25+/-12, P<0.05) and a concomitant greater increase in
      sodium excretion (84+/-12%, P<0.05) compared with control values. In contrast, in
      Ang II-infused rats (n=10) intrarenal inhibition of nNOS by L-SMTC did not cause
      significant decreases in GFR, RPF and sodium excretion (-2+/-2%, -15+/-10%, and 
      14+/-10%, respectively). These results suggest that in normotensive rats nNOS
      derived NO counteracts Ang II-mediated vasoconstriction in the pre- and
      postglomerular microcirculation. Furthermore, Ang II-infused rats exhibit an
      impaired ability to release NO by nNOS. Decreased nNOS activity is likely to
      account at least partially for the enhanced TGF responsiveness in Ang II-infused
      rats and thus may contribute to the maintenance of hypertension in this model.

PMID- 11509491
TI  - Effects of chronic clonidine administration on sympathetic nerve traffic and
      baroreflex function in heart failure.
AB  - Congestive heart failure is characterized by a sympathetic activation that is
      coupled with a baroreflex impairment. Whether these alterations are affected by
      clonidine is unknown. In 26 normotensive patients age 58.0+/-1.1 years (mean+/
      SEM) affected by congestive heart failure (New York Heart Association functional
      class II or III) and treated with furosemide and enalapril, we measured mean
      arterial pressure, heart rate, venous plasma norepinephrine, and muscle
      sympathetic nerve traffic (microneurography) at rest and during baroreceptor
      stimulation and deactivation caused by stepwise intravenous infusions of
      phenylephrine and nitroprusside, respectively. Measurements were repeated after a
      2-month administration of transdermal clonidine patch (14 patients) or placebo
      (12 patients) according to a double-blind, randomized sequence. Clonidine caused
      a slight, nonsignificant reduction in mean arterial pressure and heart rate
      without affecting exercise capacity and echocardiographically determined left
      ventricular ejection fraction. In contrast, both plasma norepinephrine and
      sympathetic nerve traffic were significantly reduced (-46.8% and -26.7%,
      respectively; P<0.01 for both). This reduction was coupled with no change in
      cardiac and sympathetic baroreflex responses. Transdermal placebo administration
      for a 2-month period did not affect any of the above-mentioned variables. Thus,
      in congestive heart failure patients who are undergoing conventional drug
      treatment, chronic clonidine administration exerts marked sympathoinhibitory
      effects without adversely affecting cardiac functions and clinical state. Whether
      this leads to further therapeutic benefits remains to be tested.

PMID- 11509492
TI  - Negative inotropic and chronotropic effects of oxytocin.
AB  - We have previously shown that oxytocin receptors are present in the heart and
      that perfusion of isolated rat hearts with oxytocin results in decreased cardiac
      flow rate and bradycardia. The mechanisms involved in the negative inotropic and
      chronotropic effects of oxytocin were investigated in isolated dog right atria in
      the absence of central mechanisms. Perfusion of atria through the sinus node
      artery with 10(-6) mol/L oxytocin over 5 minutes (8 mL/min) significantly
      decreased both beating rate (-14.7+/-4.9% of basal levels, n=5, P<0.004) and
      force of contraction (-52.4+/-9.1% of basal levels, n=5, P<0.001). Co-perfusion
      with 10(-6) mol/L oxytocin receptor antagonist (n=3) completely inhibited the
      effects of oxytocin on frequency (P<0.04) and force of contraction (P<0.004),
      indicating receptor specificity. The effects of oxytocin were also totally
      inhibited by co-perfusion with 5x10(-8) mol/L tetrodotoxin (P<0.02) or 10(-6)
      mol/L atropine (P<0.03) but not by 10(-6) mol/L hexamethonium, which implies that
      these effects are neurally mediated, primarily by intrinsic parasympathetic
      postganglionic neurons. Co-perfusion with 10(-6) mol/L NO synthase inhibitor (L
      NAME) significantly inhibited oxytocin effects on both beating rate (-1.85+/
      1.27% versus -14.7+/-4.9% in oxytocin alone, P<0.05) and force of contraction (
      24.9+/-4.4% versus -52.4+/-9.1% in oxytocin alone, n=4, P<0.04). The effect of
      oxytocin on contractility was further inhibited by L-NAME at 10(-4) mol/L (-8.1+/
      1.8%, P<0.01). These studies imply that the negative inotropic and chronotropic
      effects of oxytocin are mediated by cardiac oxytocin receptors and that intrinsic
      cardiac cholinergic neurons and NO are involved in these actions.

PMID- 11509493
TI  - Energy-sensing and signaling by AMP-activated protein kinase in skeletal muscle.
AB  - AMP-activated protein kinase (AMPK) is emerging as an important energy
      sensing/signaling system in skeletal muscle. This kinase is activated
      allosterically by 5'-AMP and inhibited allosterically by creatine phosphate.
      Phosphorylation of AMPK by an upstream kinase, AMPK kinase (also activated
      allosterically by 5'-AMP), results in activation. It is activated in both rat and
      human muscle in response to muscle contraction, the extent of activation
      depending on work rate and muscle glycogen concentration. AMPK can also be
      activated chemically in resting muscle with 5-aminoimidazole-4-carboxamide
      riboside, which enters the muscle and is phosphorylated to form ZMP, a nucleotide
      that mimics the effect of 5'-AMP. Once activated, AMPK is hypothesized to
      phosphorylate proteins involved in triggering fatty acid oxidation and glucose
      uptake. Evidence is also accumulating for a role of AMPK in inducing some of the
      adaptations to endurance training, including the increase in muscle GLUT-4,
      hexokinase, uncoupling protein 3, and some of the mitochondrial oxidative
      enzymes. It thus appears that AMPK has the capability of monitoring intramuscular
      energy charge and then acutely stimulating fat oxidation and glucose uptake to
      counteract the increased rates of ATP utilization during muscle contraction. In
      addition, this system may have the capability of enhancing capacity for ATP
      production when the muscle is exposed to endurance training.

PMID- 11509494
TI  - Inflammatory and mechanical factors of allergen-induced bronchoconstriction in
      mild asthma and rhinitis.
AB  - We studied whether different bronchial responses to allergen in asthma and
      rhinitis are associated with different bronchial inflammation and remodeling or
      airway mechanics. Nine subjects with mild asthma and eight with rhinitis alone
      underwent methacholine and allergen inhalation challenges. The latter was
      preceded and followed by bronchoalveolar lavage and bronchial biopsy. The
      response to methacholine was positive in all asthmatic but in only two rhinitic
      subjects. The response to allergen was positive in all asthmatic and most, i.e.,
      five, rhinitic subjects. No significant differences between groups were found in
      airway inflammatory cells or basement membrane thickness either at baseline or
      after allergen. The ability of deep inhalation to dilate methacholine-constricted
      airways was greater in rhinitis than in asthma, but it was progressively reduced
      in rhinitis during allergen challenge. We conclude that 1) rhinitic subjects may
      develop similar airway inflammation and remodeling as the asthmatic subjects do
      and 2) the difference in bronchial response to allergen between asthma and
      rhinitis is associated with different airway mechanics.

PMID- 11509495
TI  - On the functional consequences of bronchial basement membrane thickening.
AB  - Reticular basement membrane (RBM) thickness and airway responses to inhaled
      methacholine (MCh) were studied in perennial allergic asthma (n = 11), perennial
      allergic rhinitis (n = 8), seasonal allergic rhinitis (n = 5), and chronic
      obstructive pulmonary disease (COPD, n = 9). RBM was significantly thicker in
      asthma (10.1 +/- 3.7 microm) and perennial rhinitis (11.2 +/- 4.2 microm) than in
      seasonal rhinitis (4.7 +/- 0.7 microm) and COPD (5.2 +/- 0.7 microm). The dose
      (geometric mean) of MCh causing a 20% decrease of 1-s forced expiratory volume
      (FEV(1)) was significantly higher in perennial rhinitis (1,073 microg) than in
      asthma (106 microg). In COPD, the slope of the linear regression of all values of
      forced vital capacity plotted against FEV(1) during the challenge was higher, and
      the intercept less, than in other groups, suggesting enhanced airway closure. In
      asthma, RBM thickness was positively correlated (r = 0.77) with the dose
      (geometric mean) of MCh causing a 20% decrease of FEV(1) and negatively
      correlated (r = -0.73) with the forced vital capacity vs. FEV(1) slope. We
      conclude that 1) RBM thickening is not unique to bronchial asthma, and 2) when
      present, it may protect against airway narrowing and air trapping. These findings
      support the opinion that RBM thickening represents an additional load on airway
      smooth muscle.

PMID- 11509496
TI  - Effects of acute creatine monohydrate supplementation on leucine kinetics and
      mixed-muscle protein synthesis.
AB  - Creatine monohydrate (CrM) supplementation during resistance exercise training
      results in a greater increase in strength and fat-free mass than placebo. Whether
      this is solely due to an increase in intracellular water or whether there may be
      alterations in protein turnover is not clear at this point. We examined the
      effects of CrM supplementation on indexes of protein metabolism in young healthy
      men (n = 13) and women (n = 14). Subjects were randomly allocated to CrM (20
      g/day for 5 days followed by 5 g/day for 3-4 days) or placebo (glucose polymers)
      and tested before and after the supplementation period under rigorous dietary and
      exercise controls. Muscle phosphocreatine, creatine, and total creatine were
      measured before and after supplementation. A primed-continuous intravenous
      infusion of L-[1-(13)C]leucine and mass spectrometry were used to measure mixed
      muscle protein fractional synthetic rate and indexes of whole body leucine
      metabolism (nonoxidative leucine disposal), leucine oxidation, and plasma leucine
      rate of appearance. CrM supplementation increased muscle total creatine (+13.1%,
      P < 0.05) with a trend toward an increase in phosphocreatine (+8.8%, P = 0.09).
      CrM supplementation did not increase muscle fractional synthetic rate but reduced
      leucine oxidation (-19.6%) and plasma leucine rate of appearance (-7.5%, P <
      0.05) in men, but not in women. CrM did not increase total body mass or fat-free
      mass. We conclude that short-term CrM supplementation may have anticatabolic
      actions in some proteins (in men), but CrM does not increase whole body or mixed
      muscle protein synthesis.

PMID- 11509497
TI  - Maximal aerobic capacity across age in healthy Hispanic and Caucasian women.
AB  - We tested the hypothesis that the age-related decline in maximal aerobic
      capacity, as measured by maximal oxygen uptake (VO(2 max)), is greater in
      Hispanic than in Caucasian women. We studied 146 healthy sedentary women aged 20
      75 yr: 53 Hispanic (primarily of Mexican descent) and 93 Caucasian (non-Hispanic
      white). The groups did not differ in mean age, body mass, percent body fat,
      estimated physical activity-related energy expenditure, or education-based
      socioeconomic status (SES). During maximal exercise, respiratory exchange ratio,
      rating of perceived exertion, and percent predicted maximal heart rate were
      similar across age and ethnicity, suggesting equivalent maximum voluntary efforts
      in all subjects. VO(2 max) (ml x kg(-1) x min(-1)) was inversely related to age
      (P < 0.01) in Caucasian (r =-0.68) and Hispanic (r = -0.61) women. The absolute
      rate of decline in VO(2 max) with age was the same in the two groups (-0.31 ml x
      kg(-1) x min(-1) x yr(-1)). The relative rate of decline (% from age 25 yr) also
      was similar in the Caucasian (-9.0%) and Hispanic (-9.2%) women. When subjects of
      all ages were pooled, mean levels of VO(2 max) were similar in the two groups
      (approximately 28 ml x kg(-1) x min(-1)). These results, the first to our
      knowledge in Hispanics, indicate that mean levels of VO(2 max), as well as the
      rate of decline in VO(2 max) with age, are similar in healthy sedentary Hispanic
      and Caucasian women of similar SES. Thus it does not appear that Hispanic
      ethnicity per se modulates maximal aerobic capacity in this population.

PMID- 11509498
TI  - Hyperthermia and central fatigue during prolonged exercise in humans.
AB  - The present study investigated the effects of hyperthermia on the contributions
      of central and peripheral factors to the development of neuromuscular fatigue.
      Fourteen men exercised at 60% maximal oxygen consumption on a cycle ergometer in
      hot (40 degrees C; hyperthermia) and thermoneutral (18 degrees C; control)
      environments. In hyperthermia, the core temperature increased throughout the
      exercise period and reached a peak value of 40.0 +/- 0.1 degrees C (mean +/- SE)
      at exhaustion after 50 +/- 3 min of exercise. In control, core temperature
      stabilized at approximately 38.0 +/- 0.1 degrees C, and exercise was maintained
      for 1 h without exhausting the subjects. Immediately after the cycle trials,
      subjects performed 2 min of sustained maximal voluntary contraction (MVC) either
      with the exercised legs (knee extension) or with a "nonexercised" muscle group
      (handgrip). The degree of voluntary activation during sustained maximal knee
      extensions was assessed by superimposing electrical stimulation (EL) to nervus
      femoralis. Voluntary knee extensor force was similar during the first 5 s of
      contraction in hyperthermia and control. Thereafter, force declined in both
      trials, but the reduction in maximal voluntary force was more pronounced in the
      hyperthermic trial, and, from 30 to 120 s, the force was significantly lower in
      hyperthermia compared with control. Calculation of the voluntary activation
      percentage (MVC/MVC + EL) revealed that the degree of central activation was
      significantly lower in hyperthermia (54 +/- 7%) compared with control (82 +/-
      6%). In contrast, total force of the knee extensors (MVC + force from EL) was not
      different in the two trials. Force development during handgrip contraction
      followed the same pattern of response as was observed for the knee extensors. In
      conclusion, these data demonstrate that the ability to generate force during a
      prolonged MVC is attenuated with hyperthermia, and the impaired performance is
      associated with a reduction in the voluntary activation percentage.

PMID- 11509499
TI  - Elevating dietary salt exacerbates hyperpnea-induced airway obstruction in guinea
      pigs.
AB  - Previous studies have indicated that increased dietary salt consumption worsens
      postexercise pulmonary function in humans with exercise-induced asthma (EIA). It
      has been suggested that EIA and hyperpnea-induced airway obstruction (HIAO) in
      guinea pigs (an animal model of EIA) are mediated by similar mechanisms.
      Therefore, the purpose of this study was to determine whether altering dietary
      salt consumption also exacerbated HIAO in guinea pigs. Furthermore, the potential
      pathway of action of dietary salt was investigated by blocking leukotriene (LT)
      production during HIAO in guinea pigs. Thirty-two male Hartley strain guinea pigs
      were split into two groups. One group (n = 16) of animals ingested a normal-salt
      diet (NSD) for 2 wk; the other group (n = 16) ingested a high-salt diet (HSD) for
      2 wk. Thereafter, animals were anesthetized, cannulated, tracheotomized, and
      mechanically ventilated during a baseline period and during two dry gas hyperpnea
      challenges. After the first challenge, the animals were administered either
      saline or nordihydroguaiaretic acid, a LT inhibitor. Bladder urine was analyzed
      for electrolyte concentrations and urinary LTE(4). The HSD elicited higher airway
      inspiratory pressures (Ptr) than the NSD (P < 0.001) postchallenge. However,
      after infusion of the LT inhibitor and a second hyperpnea challenge, HIAO was
      blocked in both diet groups (P < 0.001). Nonetheless, the HSD group continued to
      demonstrate slightly higher Ptr than the NSD group (P < 0.05). Urinary LTE(4)
      excretion significantly increased in the HSD group compared with the NSD group
      within treatment groups. This study has demonstrated that dietary salt loading
      exacerbated the development of HIAO in guinea pigs and that LT release was
      involved in HIAO and may be moderated by changes in dietary salt loading.

PMID- 11509500
TI  - Phagocytic function in cyclists: correlation with catecholamines and cortisol.
AB  - Flow cytometer measurements were made of the basal variations in peripheral blood
      functional monocytes and granulocytes over the course of a training season
      (January to November) of a cycling team. Parallel determinations were made of
      plasma concentration of catecholamines (chromatography) and cortisol (RIA) in a
      search for neuroendocrine markers. The results showed the greatest phagocytic
      capacity to occur in the central months (March, May, and July), coinciding with
      the greatest number and highest level of competitive events with good correlation
      with a peak in epinephrine during these months (r(2) = 0.998 for monocytes and
      r(2) = 0.674 for granulocytes). No good correlations were found between
      phagocytosis and norepinephrine or cortisol. The highest values for phagocytosis
      and epinephrine concentration were found in May. These results suggest that blood
      epinephrine concentration could be a good neuroendocrine marker of sportspeople's
      phagocytic response.

PMID- 11509501
TI  - Regulation of muscle GLUT-4 transcription by AMP-activated protein kinase.
AB  - Skeletal muscle GLUT-4 transcription in response to treatment with 5
      aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR), a known activator
      of AMP-activated protein kinase (AMPK), was studied in rats and mice. The
      increase in GLUT-4 mRNA levels in response to a single subcutaneous injection of
      AICAR, peaked at 13 h in white and red quadriceps muscles but not in the soleus
      muscle. The mRNA level of chloramphenicol acyltransferase reporter gene which is
      driven by 1,154 or 895 bp of the human GLUT-4 proximal promoter was increased in
      AICAR-treated transgenic mice, demonstrating the transcriptional upregulation of
      the GLUT-4 gene by AICAR. However, this induction of transcription was not
      apparent with 730 bp of the promoter. In addition, nuclear extracts from AICAR
      treated mice bound to the consensus sequence of myocyte enhancer factor-2 (from 
      473 to -464) to a greater extent than from saline-injected mice. Thus AMP
      activated protein kinase activation by AICAR increases GLUT-4 transcription by a
      mechanism that requires response elements within 895 bp of human GLUT-4 proximal
      promoter and that may be cooperatively mediated by myocyte enhancer factor-2.

PMID- 11509502
TI  - Effect of mechanical deformation of neutrophils on their CD18/ICAM-1-dependent
      adhesion.
AB  - Mechanical deformation of polymorphonuclear leukocytes (PMN) changes their
      expression of the surface adhesion molecule CD11b/CD18. We tested the hypothesis
      that mechanical deformation of PMN enhances their adhesiveness. Purified human
      PMN were deformed through either 5- or 3-microm polycarbonate membrane filters
      and allowed to adhere to 96-well plates coated with human recombinant
      intercellular adhesion molecule-1 (ICAM-1). Flow cytometric studies showed that
      deformation of PMN increased CD11b/CD18 expression (P < 0.01). PMN adhesion to
      ICAM-1-coated plates was dependent on the magnitude of cell deformation (5
      microm, 63.8 +/- 8.1%, P < 0.04; 3 microm, 232.4 +/- 20.9%, P < 0.01). Priming of
      PMN (0.5 nM N-formyl-methionyl-leucyl-phenylalanine) before deformation (5
      microm) increased PMN adhesion (63.8 +/- 8.1 vs. 105.3 +/- 16.4%; P < 0.04).
      Stimulation (5% zymosan-activated plasma) of PMN after deformation resulted in
      increased adhesion, and the degree of increase was dependent on the magnitude of
      PMN deformation (stimulation, 50.6 +/- 4%; 5-microm filtration and stimulation,
      62.9 +/- 6.6%; 3-microm filtration and stimulation, 249.9 +/- 24.2%; P < 0.01).
      This study shows that mechanical deformation of PMN causes an increase in PMN
      adhesiveness to ICAM-1 that was enhanced by both priming of PMN before
      deformation and stimulation after cell deformation.

PMID- 11509503
TI  - Hindlimb unweighting decreases endothelium-dependent dilation and eNOS expression
      in soleus not gastrocnemius.
AB  - We tested the hypothesis that hindlimb unweighting (HLU) decreases endothelium
      dependent vasodilation and expression of endothelial nitric oxide synthase (eNOS)
      and superoxide dismutase-1 (SOD-1) in arteries of skeletal muscle with reduced
      blood flow during HLU. Sprague-Dawley rats (300-350 g) were exposed to HLU (n =
      15) or control (n = 15) conditions for 14 days. ACh-induced dilation was assessed
      in muscle with reduced [soleus (Sol)] or unchanged [gastrocnemius (Gast)] blood
      flow during HLU. eNOS and SOD-1 expression were measured in feed arteries (FA)
      and in first-order (1A), second-order (2A), and third-order (3A) arterioles.
      Dilation to infusion of ACh in vivo was blunted in Sol but not Gast. In arteries
      of Sol muscle, HLU decreased eNOS mRNA and protein content. eNOS mRNA content was
      significantly less in Sol FA (35%), 1A arterioles (25%) and 2A arterioles (18%).
      eNOS protein content was less in Sol FA (64%) and 1A arterioles (65%) from HLU
      rats. In arteries of Gast, HLU did not decrease eNOS mRNA or protein. SOD-1 mRNA
      expression was less in Sol 2A arterioles (31%) and 3A arterioles (29%) of HLU
      rats. SOD-1 protein content was less in Sol FA (67%) but not arterioles. SOD-1
      mRNA and protein content were not decreased in arteries from Gast. These data
      indicate that HLU decreases endothelium-dependent vasodilation, eNOS expression,
      and SOD-1 expression primarily in arteries of Sol muscle where blood flow is
      reduced during HLU.

PMID- 11509504
TI  - Effects of acute exercise on the gluconeogenic capacity of periportal and
      perivenous hepatocytes.
AB  - The present study was conducted to examine the effect of a single bout of
      exercise (rodent treadmill, 60 min at 26 m/min, 0% grade) on the gluconeogenic
      activity of periportal hepatocytes (PP-H) and perivenous hepatocytes (PV-H) in
      fasted (18 h) rats. Isolated PP-H and PV-H, obtained by selective destruction
      following liver perfusion with digitonin and collagenase, were incubated with
      saturating concentrations of alanine (Ala; 20 mM) or a mixture of lactate and
      pyruvate (Lac+Pyr; 20:2 mM) to determine the glucose production flux (J(glucose))
      in the incubation medium. Results show that, in the resting conditions,
      J(glucose) from all exogenous substrates was significantly higher (P < 0.01) in
      PP-H than in PV-H. Exercise, compared with rest, resulted in a higher J(glucose)
      (P < 0.01) from Lac+Pyr substrate in the PV-H but not in the PP-H, resulting in
      the disappearance of the difference in J(glucose) between PP-H and PV-H.
      Exercise, compared with rest, led to a higher J(glucose) (P < 0.01) from Ala
      substrate in both PP-H and PV-H. However, the exercise-induced increase in
      J(glucose) (gluconeogenic activity) from Ala substrate was higher in PV-H than in
      PP-H, resulting, as from Lac+Pyr substrate, in the disappearance (P > 0.05) of
      the difference of J(glucose) between PP-H and PV-H. It is concluded that exercise
      differentially stimulates the gluconeogenic activity of PV-H to a larger extent
      than PP-H, indicative of a heterogeneous metabolic response of hepatocytes to
      exercise.

PMID- 11509505
TI  - Nitric oxide synthase inhibition does not affect the exercise-induced arterial
      hypoxemia in Thoroughbred horses.
AB  - Because sensitivity of equine pulmonary vasculature to endogenous as well as
      exogenous nitric oxide (NO) has been demonstrated, we examined whether endogenous
      NO production plays a role in exercise-induced arterial hypoxemia. We
      hypothesized that inhibition of NO synthase may alter the distribution of
      ventilation-perfusion mismatching, which may affect the exercise-induced arterial
      hypoxemia. Arterial blood-gas variables were examined in seven healthy, sound
      Thoroughbred horses at rest and during incremental exercise protocol leading to
      galloping at maximal heart rate without (control; placebo = saline) and with
      N(omega)-nitro-L-arginine methyl ester (L-NAME) administration (20 mg/kg iv). The
      experiments were carried out in random order, 7 days apart. At rest, L-NAME
      administration caused systemic hypertension, pulmonary hypertension, and
      bradycardia. During 120 s of galloping at maximal heart rate, significant
      arterial hypoxemia, desaturation of hemoglobin, hypercapnia, hyperthermia, and
      acidosis occurred in the control as well as in NO synthase inhibition
      experiments. However, statistically significant differences between the
      treatments were not found. In both treatments, exercise caused a significant rise
      in hemoglobin concentration, but the increment was significantly attenuated in
      the NO synthase inhibition experiments, and, therefore, arterial O(2) content
      (Ca(O(2))) increased to significantly lower values. These data suggest that,
      whereas L-NAME administration does not affect pulmonary gas exchange in
      exercising horses, it may affect splenic contraction, which via an attenuation of
      the rise in hemoglobin concentration and Ca(O(2)) may limit performance at higher
      workloads.

PMID- 11509506
TI  - "Living high-training low" altitude training improves sea level performance in
      male and female elite runners.
AB  - Acclimatization to moderate high altitude accompanied by training at low altitude
      (living high-training low) has been shown to improve sea level endurance
      performance in accomplished, but not elite, runners. Whether elite athletes, who
      may be closer to the maximal structural and functional adaptive capacity of the
      respiratory (i.e., oxygen transport from environment to mitochondria) system, may
      achieve similar performance gains is unclear. To answer this question, we studied
      14 elite men and 8 elite women before and after 27 days of living at 2,500 m
      while performing high-intensity training at 1,250 m. The altitude sojourn began 1
      wk after the USA Track and Field National Championships, when the athletes were
      close to their season's fitness peak. Sea level 3,000-m time trial performance
      was significantly improved by 1.1% (95% confidence limits 0.3-1.9%). One-third of
      the athletes achieved personal best times for the distance after the altitude
      training camp. The improvement in running performance was accompanied by a 3%
      improvement in maximal oxygen uptake (72.1 +/- 1.5 to 74.4 +/- 1.5 ml x kg(-1) x
      min(-1)). Circulating erythropoietin levels were near double initial sea level
      values 20 h after ascent (8.5 +/- 0.5 to 16.2 +/- 1.0 IU/ml). Soluble transferrin
      receptor levels were significantly elevated on the 19th day at altitude,
      confirming a stimulation of erythropoiesis (2.1 +/- 0.7 to 2.5 +/- 0.6
      microg/ml). Hb concentration measured at sea level increased 1 g/dl over the
      course of the camp (13.3 +/- 0.2 to 14.3 +/- 0.2 g/dl). We conclude that 4 wk of
      acclimatization to moderate altitude, accompanied by high-intensity training at
      low altitude, improves sea level endurance performance even in elite runners.
      Both the mechanism and magnitude of the effect appear similar to that observed in
      less accomplished runners, even for athletes who may have achieved near maximal
      oxygen transport capacity for humans.

PMID- 11509507
TI  - Role of airway nitric oxide on the regulation of pulmonary circulation by carbon
      dioxide.
AB  - The effects of hypercapnia (CO(2)) confined to either the alveolar space or the
      intravascular perfusate on exhaled nitric oxide (NO), perfusate NO metabolites
      (NOx), and pulmonary arterial pressure (Ppa) were examined during normoxia and
      progressive 20-min hypoxia in isolated blood- and buffer-perfused rabbit lungs.
      In blood-perfused lungs, when alveolar CO(2) concentration was increased from 0
      to 12%, exhaled NO decreased, whereas Ppa increased. Increments of intravascular
      CO(2) levels increased Ppa without changes in exhaled NO. In buffer-perfused
      lungs, alveolar CO(2) increased Ppa with reductions in both exhaled NO from 93.8
      to 61.7 (SE) nl/min (P < 0.01) and perfusate NOx from 4.8 to 1.8 nmol/min (P <
      0.01). In contrast, intravascular CO(2) did not affect either exhaled NO or Ppa
      despite a tendency for perfusate NOx to decline. Progressive hypoxia elevated Ppa
      by 28% from baseline with a reduction in exhaled NO during normocapnia. Alveolar
      hypercapnia enhanced hypoxic Ppa response up to 50% with a further decline in
      exhaled NO. Hypercapnia did not alter the apparent K(m) for O(2), whereas it
      significantly decreased the V(max) from 66.7 to 55.6 nl/min. These results
      suggest that alveolar CO(2) inhibits epithelial NO synthase activity
      noncompetitively and that the suppressed NO production by hypercapnia augments
      hypoxic pulmonary vasoconstriction, resulting in improved ventilation-perfusion
      matching.

PMID- 11509508
TI  - Homeokinesis and short-term variability of human airway caliber.
AB  - We hypothesized that short-term variation in airway caliber could be quantified
      by frequency distributions of respiratory impedance (Zrs) measured at high
      frequency. We measured Zrs at 6 Hz by forced oscillations during quiet breathing
      for 15 min in 10 seated asthmatic patients and 6 normal subjects in upright and
      supine positions before and after methacholine (MCh). We plotted frequency
      distributions of Zrs and calculated means, skewness, kurtosis, and significance
      of differences between normal and log-normal frequency distributions. The data
      were close to, but usually significantly different from, a log-normal frequency
      distribution. Mean lnZrs in upright and supine positions was significantly less
      in normal subjects than in asthmatic patients, but not after MCh and MCh in the
      supine position. The lnZrs SD (a measure of variation), in the upright position
      and after MCh was significantly less in normal subjects than in asthmatic
      patients, but not in normal subjects in the supine position and after MCh in the
      supine position. We conclude that 1) the configuration of the normal
      tracheobronchial tree is continuously changing and that this change is
      exaggerated in asthma, 2) in normal lungs, control of airway caliber is
      homeokinetic, maintaining variation within acceptable limits, 3) normal airway
      smooth muscle (ASM) when activated and unloaded closely mimics asthmatic ASM, 4)
      in asthma, generalized airway narrowing results primarily from ASM activation,
      whereas ASM unloading by increasing shortening velocity allows faster caliber
      fluctuations, 5) activation moves ASM farther from thermodynamic equilibrium, and
      6) asthma may be a low-entropy disease exhibiting not only generalized airway
      narrowing but also an increased appearance of statistically unlikely airway
      configurations.

PMID- 11509509
TI  - Muscarinic excitation-contraction coupling mechanisms in tracheal and bronchial
      smooth muscles.
AB  - We investigated the mechanisms underlying muscarinic excitation-contraction
      coupling in canine airway smooth muscle using organ bath, fura 2 fluorimetric,
      and patch-clamp techniques. Cyclopiazonic acid (CPA) augmented the responses to
      submaximal muscarinic stimulation in both tracheal (TSM) and bronchial smooth
      muscles (BSM), consistent with disruption of the barrier function of the
      sarcoplasmic reticulum. During maximal stimulation, however, CPA evoked
      substantial relaxation in TSM but not BSM. CPA reversal of carbachol tone
      persisted in the presence of tetraethylammoium or high KCl, suggesting that
      hyperpolarization is not involved; CPA relaxations were absent in tissues
      preconstricted with KCl alone or by permeabilization with beta-escin, ruling out
      a nonspecific effect on the contractile apparatus. Peak contractions were
      sensitive to inhibitors of tyrosine kinase (genistein) or Rho kinase (Y-27632).
      Sustained responses were dependent on Ca(2+) influx in TSM but not BSM; this
      influx was sensitive to Ni(2+) but not La(3+). In conclusion, there are several
      mechanisms underlying excitation-contraction coupling in airway smooth muscle,
      the relative importance of which varies depending on tissue and degree of
      stimulation.

PMID- 11509510
TI  - Measurement of cell microrheology by magnetic twisting cytometry with frequency
      domain demodulation.
AB  - Magnetic twisting cytometry (MTC) (Wang N, Butler JP, and Ingber DE, Science 260:
      1124-1127, 1993) is a useful technique for probing cell micromechanics. The
      technique is based on twisting ligand-coated magnetic microbeads bound to
      membrane receptors and measuring the resulting bead rotation with a magnetometer.
      Owing to the low signal-to-noise ratio, however, the magnetic signal must be
      modulated, which is accomplished by spinning the sample at approximately 10 Hz.
      Present demodulation approaches limit the MTC range to frequencies <0.5 Hz. We
      propose a novel demodulation algorithm to expand the frequency range of MTC
      measurements to higher frequencies. The algorithm is based on coherent
      demodulation in the frequency domain, and its frequency range is limited only by
      the dynamic response of the magnetometer. Using the new algorithm, we measured
      the complex modulus of elasticity (G*) of cultured human bronchial epithelial
      cells (BEAS-2B) from 0.03 to 16 Hz. Cells were cultured in supplemented RPMI
      medium, and ferromagnetic beads (approximately 5 microm) coated with an RGD
      peptide were bound to the cell membrane. Both the storage (G', real part of G*)
      and loss (G", imaginary part of G*) moduli increased with frequency as
      omega(alpha) (2 pi x frequency) with alpha approximately equal to 1/4. The ratio
      G"/G' was approximately 0.5 and varied little with frequency. Thus the cells
      exhibited a predominantly elastic behavior with a weak power law of frequency and
      a nearly constant proportion of elastic vs. frictional stresses, implying that
      the mechanical behavior conformed to the so-called structural damping (or
      constant-phase) law (Maksym GN, Fabry B, Butler JP, Navajas D, Tschumperlin DJ,
      LaPorte JD, and Fredberg JJ, J Appl Physiol 89: 1619-1632, 2000). We conclude
      that frequency domain demodulation dramatically increases the frequency range
      that can be probed with MTC and reveals that the mechanics of these cells
      conforms to constant-phase behavior over a range of frequencies approaching three
      decades.

PMID- 11509511
TI  - Leukotriene B(4) promotes reactive oxidant generation and leukocyte adherence
      during acute hypoxia.
AB  - Acute systemic hypoxia produces rapid leukocyte adherence in the rat mesenteric
      microcirculation, although the underlying mechanisms are not fully known. Hypoxia
      is known to increase reactive oxygen species (ROS) generation, which could result
      in formation of the lipid inflammatory mediator leukotriene B(4) (LTB(4)). The
      goal of this study was to examine the role of LTB(4) in hypoxia-induced
      microvascular alterations. Using intravital microscopy, we determined the effect
      of the LTB(4) antagonist, LTB(4)-dimethyl amide (LTB(4)-DMA), on ROS generation
      and leukocyte adherence in mesenteric venules during hypoxia. Exogenous LTB(4)
      increased ROS generation to 144 +/- 8% compared with control values and also
      promoted leukocyte adherence. These responses to LTB(4) were blocked by
      pretreating the mesentery with LTB(4)-DMA. Leukopenia did not significantly
      attenuate the LTB(4)-induced increase in ROS generation (142 +/- 12.1%). LTB(4)
      DMA substantially, though not completely, reduced hypoxia-induced ROS generation
      from 66 +/- 18% to 11 +/- 4% above control values. Hypoxia-induced leukocyte
      adherence was significantly attenuated by LTB(4)-DMA. Our results support a role
      for LTB(4) in the mechanism of hypoxia-induced ROS generation and leukocyte
      adherence in the rat mesenteric microcirculation.

PMID- 11509512
TI  - Effects of a 12-wk resistance exercise program on skeletal muscle strength in
      children with burn injuries.
AB  - The posttraumatic response to burn injury leads to marked and prolonged skeletal
      muscle catabolism and weakness, which persist despite standard rehabilitation
      programs of occupational and physical therapy. We investigated whether a
      resistance exercise program would attenuate muscle loss and weakness that is
      typically found in children with thermal injury. We assessed the changes in leg
      muscle strength and lean body mass in severely burned children with >40% total
      body surface area burned. Patients were randomized to a 12-wk standard hospital
      rehabilitation program supplemented with an exercise training program (n = 19) or
      to a home-based rehabilitation program without exercise (n = 16). Leg muscle
      strength was assessed before and after the 12-wk rehabilitation or training
      program at an isokinetic speed of 150 degrees /s. Lean body mass was assessed
      using dual-energy X-ray absorptiometry. We found that the participation in a
      resistance exercise program results in a significant improvement in muscle
      strength, power, and lean body mass relative to a standard rehabilitation program
      without exercise.

PMID- 11509513
TI  - Skeletal muscle capillarity and angiogenic mRNA levels after exercise training in
      normoxia and chronic hypoxia.
AB  - Gene expression of vascular endothelial growth factor (VEGF), and to a lesser
      extent of transforming growth factor-beta(1) (TGF-beta(1)) and basic fibroblast
      growth factor (bFGF), has been found to increase in rat skeletal muscle after a
      single exercise bout. In addition, acute hypoxia augments the VEGF mRNA response
      to exercise, which suggests that, if VEGF is important in muscle angiogenesis,
      hypoxic training might produce greater capillary growth than normoxic training.
      Therefore, we examined the effects of exercise training (treadmill running at the
      same absolute intensity) in normoxia and hypoxia (inspired O(2) fraction = 0.12)
      on rat skeletal muscle capillarity and on resting and postexercise gene
      expression of VEGF, its major receptors (flt-1 and flk-1), TGF-beta(1), and bFGF.
      Normoxic training did not alter basal or exercise-induced VEGF mRNA levels but
      produced a modest twofold increase in bFGF mRNA (P < 0.05). Rats trained in
      hypoxia exhibited an attenuated VEGF mRNA response to exercise (1.8-fold compared
      3.4-fold with normoxic training; P < 0.05), absent TGF-beta(1) and flt-1 mRNA
      responses to exercise, and an approximately threefold (P < 0.05) decrease in bFGF
      mRNA levels. flk-1 mRNA levels were not significantly altered by either normoxic
      or hypoxic training. An increase in skeletal muscle capillarity was observed only
      in hypoxically trained rats. These data show that, whereas training in hypoxia
      potentiates the adaptive angiogenic response of skeletal muscle to a given
      absolute intensity of exercise, this was not evident in the gene expression of
      VEGF or its receptors when assessed at the end of training.

PMID- 11509514
TI  - Airway stability and heterogeneity in the constricted lung.
AB  - The effect of bronchoconstriction on airway resistance is known to be spatially
      heterogeneous and dependent on tidal volume. We present a model of a single
      terminal airway that explains these features. The model describes a feedback
      between flow and airway resistance mediated by parenchymal interdependence and
      the mechanics of activated smooth muscle. The pressure-tidal volume relationship
      for a constricted terminal airway is computed and shown to be sigmoidal.
      Constricted terminal airways are predicted to have two stable states: one
      effectively open and one nearly closed. We argue that the heterogeneity of whole
      lung constriction is a consequence of this behavior. Airways are partitioned
      between the two states to accommodate total flow, and changes in tidal volume and
      end-expiratory pressure affect the number of airways in each state. Quantitative
      predictions for whole lung resistance and elastance agree with data from
      previously published studies on lung impedance.

PMID- 11509515
TI  - Downregulation of nitric oxide in the brain of mice during their hypoxic
      preconditioning.
AB  - An animal model of hypoxic preconditioning was produced in mice by repeated
      exposure to autohypoxic condition. The animals' tolerance times to hypoxia were
      1.7, 1.8, 2.1, and 2.3 times longer in runs 2, 3, 4, and 5, respectively, than
      that in run 1, and their oxygen consumption and heart and respiration rates were
      progressively and significantly slowed down during the repetitive exposure to
      hypoxia. L-Arginine concentration, nitric oxide (NO) synthase-positive cells, NO
      synthase activity, and NO content in the whole brain and the subregions
      telencephalon, diencephalon, and brain stem were significantly increased during
      the first exposure and were, instead of continuing to increase, significantly
      decreased in run 4 after the second and third exposure. Tolerance times under the
      hypoxic condition were significantly shortened and prolonged when
      preadministration of L-arginine and its analog, respectively, was made. These
      results indicate that NO in the brain is downregulated under condition of hypoxic
      preconditioning and negatively involved in increased tolerance to hypoxia.

PMID- 11509516
TI  - Automated quantification of sympathetic beat-by-beat activity, independent of
      signal quality.
AB  - Sympathetic nerve activity (SNA) can provide critical information on
      cardiovascular regulation; however, in a typical laboratory setting, adequate
      recordings require assiduous effort, and otherwise high-quality recordings may be
      clouded by frequent baseline shifts, noise spikes, and muscle twitches. Visually
      analyzing this type of signal can be a tedious and subjective evaluation, whereas
      objective analysis through signal averaging is impossible. We propose a new
      automated technique to identify bursts through objective detection criteria,
      eliminating artifacts and preserving a beat-by-beat SNA signal for a variety of
      subsequent analyses. The technique was evaluated during both steady-state
      conditions (17 subjects) and dynamic changes with rapid vasoactive drug infusion
      (14 recordings from 5 subjects) on SNA signals of widely varied quality.
      Automated measures of SNA were highly correlated to visual measures of steady
      state activity (r = 0.903, P < 0.001), dynamic relation measures (r = 0.987, P <
      0.001), and measures of burst-by-burst variability (r = 0.929, P < 0.001). This
      automated sympathetic neurogram analysis provides a viable alternative to tedious
      and subjective visual analyses while maximizing the usability of noisy nerve
      tracings.

PMID- 11509517
TI  - Effect of short-term microgravity and long-term hindlimb unloading on rat cardiac
      mass and function.
AB  - The purpose of this study was to test the hypothesis that exposure to short-term
      microgravity or long-term hindlimb unloading induces cardiac atrophy in male
      Sprague-Dawley rats. For the microgravity study, rats were subdivided into four
      groups: preflight (PF, n = 12); flight (Fl, n = 7); flight cage simulation (Sim,
      n = 6), and vivarium control (Viv, n = 7). Animals in the Fl group were exposed
      to 7 days of microgravity during the Spacelab 3 mission. Animals in the hindlimb
      unloading study were subdivided into three groups: control (Con, n = 20), 7-day
      hindlimb-unloaded (7HU, n = 10), and 28-day hindlimb-unloaded (28HU, n = 19).
      Heart mass was unchanged in adult animals exposed to 7 days of actual
      microgravity (PF 1.33 +/- 0.03 g; Fl 1.32 +/- 0.02 g; Sim 1.28 +/- 0.04 g; Viv
      1.35 +/- 0.04 g). Similarly, heart mass was unaltered with hindlimb unloading
      (Con 1.40 +/- 0.04 g; 7HU 1.35 +/- 0.06 g; 28HU 1.42 +/- 0.03 g). Hindlimb
      unloading also had no effect on the peak rate of rise in left ventricular
      pressure, an estimate of myocardial contractility (Con 8,055 +/- 385 mmHg/s; 28HU
      8,545 +/- 755 mmHg/s). These data suggest that cardiac atrophy does not occur
      after short-term exposure to microgravity and that neither short- nor long-term
      simulated microgravity alters cardiac mass or function.

PMID- 11509518
TI  - Effects of bright light and melatonin on sleep propensity, temperature, and
      cardiac activity at night.
AB  - Melatonin increases sleepiness, decreases core temperature, and increases
      peripheral temperature in humans. Melatonin may produce these effects by
      activating peripheral receptors or altering autonomic activity. The latter
      hypothesis was investigated in 16 supine subjects. Three conditions were created
      by using bright light and exogenous melatonin: normal endogenous, suppressed, and
      pharmacological melatonin levels. Data during wakefulness from 1.5 h before to
      2.5 h after each subject's estimated melatonin onset (wake time + 14 h) were
      analyzed. Respiratory sinus arrhythmia (cardiac parasympathetic activity) and
      preejection period (cardiac sympathetic activity) did not vary among conditions.
      Pharmacological melatonin levels significantly decreased systolic blood pressure
      [5.75 +/- 1.65 (SE) mmHg] but did not significantly change heart rate. Suppressed
      melatonin significantly increased rectal temperature (0.27 +/- 0.06 degrees C),
      decreased foot temperature (1.98 +/- 0.70 degrees C), and increased sleep onset
      latency (5.53 +/- 1.87 min). Thus melatonin does not significantly alter cardiac
      autonomic activity and instead may bind to peripheral receptors in the
      vasculature and heart. Furthermore, increases in cardiac parasympathetic activity
      before normal nighttime sleep cannot be attributed to the concomitant increase in
      endogenous melatonin.

PMID- 11509519
TI  - Effect of lymphatic outflow pressure on lymphatic albumin transport in humans.
AB  - The effects of posture on the lymphatic outflow pressure and lymphatic return of
      albumin were examined in 10 volunteers. Lymph flow was stimulated with a bolus
      infusion of isotonic saline (0.9%, 12.6 ml/kg body wt) under four separate
      conditions: upright rest (Up), upright rest with lower body positive pressure
      (LBPP), supine rest (Sup), and supine rest with lower body negative pressure
      (LBNP). The increase in plasma albumin content (Delta Alb) during the 2 h after
      bolus saline infusion was greater in Up than in LBPP: 82.9 +/- 18.5 vs. -28.4
      mg/kg body wt. Delta Alb was greater in LBNP than in Sup: 92.6 vs. -22.5 +/- 18.9
      mg/kg body wt (P < 0.05). The greater Delta Alb in Up and Sup with LBNP were
      associated with a lower estimated lymphatic outflow pressure on the basis of the
      difference in central venous pressure (Delta CVP). During LBPP, CVP was increased
      compared with Up: 3.8 +/- 1.4 vs. -1.2 +/- 1.2 mmHg. During LBNP, CVP was reduced
      compared with Sup: -3.0 +/- 2.2 vs. 1.7 +/- 1.0 mmHg. The translocation of
      protein into the vascular space after bolus saline infusion reflects lymph return
      of protein and is higher in Up than in Sup. Modulation of CVP with LBPP or LBNP
      in Up and Sup, respectively, reversed the impact of posture on lymphatic outflow
      pressure. Thus posture-dependent changes in lymphatic protein transport are
      modulated by changes in CVP through its mechanical impact on lymphatic outflow
      pressure.

PMID- 11509520
TI  - Increased renal tubular sodium reabsorption during exercise-induced hypervolemia
      in humans.
AB  - We tested the hypothesis that renal tubular Na(+) reabsorption increased during
      the first 24 h of exercise-induced plasma volume expansion. Renal function was
      assessed 1 day after no-exercise control (C) or intermittent cycle ergometer
      exercise (Ex, 85% of peak O(2) uptake) for 2 h before and 3 h after saline
      loading (12.5 ml/kg over 30 min) in seven subjects. Ex reduced renal blood flow
      (p-aminohippurate clearance) compared with C (0.83 +/- 0.12 vs. 1.49 +/- 0.24
      l/min, P < 0.05) but did not influence glomerular filtration rates (97 +/- 10
      ml/min, inulin clearance). Fractional tubular reabsorption of Na(+) in the
      proximal tubules was higher in Ex than in C (P < 0.05). Saline loading decreased
      fractional tubular reabsorption of Na(+) from 99.1 +/- 0.1 to 98.7 +/- 0.1% (P <
      0.05) in C but not in Ex (99.3 +/- 0.1 to 99.4 +/- 0.1%). Saline loading reduced
      plasma renin activity and plasma arginine vasopressin levels in C and Ex,
      although the magnitude of decrease was greater in C (P < 0.05). These results
      indicate that, during the acute phase of exercise-induced plasma volume
      expansion, increased tubular Na(+) reabsorption is directed primarily to the
      proximal tubules and is associated with a decrease in renal blood flow. In
      addition, saline infusion caused a smaller reduction in fluid-regulating hormones
      in Ex. The attenuated volume-regulatory response acts to preserve distal tubular
      Na(+) reabsorption during saline infusion 24 h after exercise.

PMID- 11509521
TI  - Glucose uptake and metabolic stress in rat muscles stimulated electrically with
      different protocols.
AB  - In the present study, the relationship between the pattern of electrical
      stimulation and glucose uptake was investigated in slow-twitch muscles (soleus)
      and fast-twitch muscles (epitrochlearis) from Wistar rats. Muscles were
      stimulated electrically for 30 min in vitro with either single pulses
      (frequencies varied between 0.8 and 15 Hz) or with 200-ms trains (0.1-2 Hz).
      Glucose uptake (measured with tracer amount of 2-[(3)H]deoxyglucose) increased
      with increasing number of impulses whether delivered as single pulses or as short
      trains. The highest glucose uptake achieved with short tetanic contractions was
      similar in soleus and epitrochlearis (10.9 +/- 0.7 and 12.0 +/- 0.8 mmol x kg dry
      wt(-1) x 30 min(-1), respectively). Single pulses, on the other hand, increased
      contraction-stimulated glucose uptake less in soleus than in epitrochlearis (7.5
      +/- 1.1 and 11.7 +/- 0.5 mmol x kg dry wt(-1) x 30 min(-1), respectively; P <
      0.02). Glucose uptake correlated with glycogen breakdown in soleus (r = 0.84, P <
      0.0001) and (epitrochlearis: r = 0.91, P < 0.0001). Contraction-stimulated
      glucose uptake also correlated with breakdown of ATP and PCr and with reduction
      in force. Our data suggest that metabolic stress mediates contraction-stimulated
      glucose uptake.

PMID- 11509522
TI  - Decreased neuronal excitability in hippocampal neurons of mice exposed to cyclic
      hypoxia.
AB  - To study the physiological effects of chronic intermittent hypoxia on neuronal
      excitability and function in mice, we exposed animals to cyclic hypoxia for 8 h
      daily (12 cycles/h) for approximately 4 wk, starting at 2-3 days of age, and
      examined the properties of freshly dissociated hippocampal neurons in vitro.
      Compared with control (Con) hippocampal CA1 neurons, exposed (Cyc) neurons showed
      action potentials (AP) with a smaller amplitude and a longer duration and a more
      depolarized resting membrane potential. They also have a lower rate of
      spontaneous firing of AP and a higher rheobase. Furthermore, there was
      downregulation of the Na(+) current density in Cyc compared with Con neurons
      (356.09 +/- 54.03 pA/pF in Cyc neurons vs. 508.48 +/- 67.30 pA/pF in Con, P <
      0.04). Na(+) channel characteristics, including activation, steady-state
      inactivation, and recovery from inactivation, were similar in both groups. The
      deactivation rate, however, was much larger in Cyc than in Con (at -100 mV, time
      constant for deactivation = 0.37 +/- 0.04 ms in Cyc neurons and 0.18 +/- 0.01 ms
      in Con neurons). We conclude that the decreased neuronal excitability in mice
      neurons treated with cyclic hypoxia is due, at least in part, to differences in
      passive properties (e.g., resting membrane potential) and in Na(+) channel
      expression and/or regulation. We hypothesize that this decreased excitability is
      an adaptive response that attempts to decrease the energy expenditure that is
      used for adjusting disturbances in ionic homeostasis in low-O(2) conditions.

PMID- 11509523
TI  - LH secretion and testosterone concentrations are blunted after resistance
      exercise in men.
AB  - This study examined the hypothesis that exercise-induced changes in circulating
      testosterone would be centrally mediated via hypothalamic-pituitary release of
      luteinizing hormone (LH). We tested this hypothesis by examining overnight LH,
      total and free testosterone (TT and FT), and cortisol (C) concentrations in 10
      young healthy men (21 +/- 1 yr) during two experimental sessions: a control and
      an acute heavy-resistance exercise bout (50 total sets consisting of squats,
      bench press, leg press, and latissimus dorsi pull-down). Exercise was performed
      from 1500 to 1700, and blood sampling began at 1700 and continued until 0600 the
      next morning. Blood was sampled every 10 min for LH and every hour for TT, FT,
      and C. Hormonal concentrations were determined via RIA, and the secretion
      characteristics of LH were analyzed with deconvolution analysis. When overnight
      postexercise concentrations were compared with control concentrations, no
      statistically significant (P < or = 0.05) differences were observed for LH half
      life, LH pulse frequency, interpulse interval, pulse amplitude, or pulse mass.
      Significant differences were observed for LH production rate (13.6 +/- 4 and 17.9
      +/- 5 IU. l distribution volume(-1) x day(-1) for exercise and control,
      respectively, a 24% reduction). For the ANOVA marginal main effect means due to
      condition, C was significantly elevated (5.9 +/- 0.7 vs. 4.0 +/- 0.4 microg/dl),
      while TT (464 +/- 23 vs. 529 +/- 32 ng/dl) and FT (15.6 +/- 0.7 vs. 18.3 +/- 0.9
      pg/ml) were significantly decreased for the exercise condition. These data
      demonstrate that the decline in overnight testosterone concentrations after acute
      heavy-resistance exercise is accompanied by a blunted LH production rate and
      elevated C concentrations.

PMID- 11509524
TI  - Effect of race and resistance training status on the density of fat-free mass and
      percent fat estimates.
AB  - The impact of race and resistance training status on the assumed density of the
      fat-free mass (D(FFM)) and estimates of body fatness via hydrodensitometry
      (%Fat(D)) vs. a four-component model (density, water, mineral; %Fat(D,W,M)) were
      determined in 45 men: white controls (W; n = 15), black controls (B; n = 15), and
      resistance-trained blacks (B-RT; n = 15). Body density by hydrostatic weighing,
      body water by deuterium dilution, and bone mineral by dual-energy X-ray
      absorptiometry were used to estimate %Fat(D,W,M). D(FFM) was not different
      between B and W (or 1.1 g/ml); however, D(FFM) in B-RT was significantly lower
      (1.091 +/- 0.012 g/ml; P < 0.05). Therefore, %Fat(D) using the Siri equation was
      not different from %Fat(D,W,M) in W (17.5 +/- 5.0 vs. 18.3 +/- 5.4%) or B (14.9
      +/- 5.6 vs. 15.7 +/- 5.7%) but significantly overestimated %Fat(D,W,M) in B-RT
      (14.0 +/- 5.9 vs. 10.4 +/- 6.0%; P < 0.05). The use of a race-specific equation
      (assuming D(FFM) = 1.113 g/ml) did not improve the agreement between %Fat(D) and
      %Fat(D,W,M), resulting in a significantly greater mean (+/-SD) discrepancy for B
      (1.7 +/- 1.8% fat) and B-RT (6.2 +/- 4.3% fat). Thus race per se does not affect
      D(FFM) or estimates of %Fat(D); however, B-RT have a D(FFM) lower than 1.1 g/ml,
      leading to an overestimation of %Fat(D).

PMID- 11509525
TI  - Effect of Rho-kinase inhibition on vasoconstriction in the penile circulation.
AB  - A recent report from this laboratory (Chitaley K, Wingard C, Webb R, Branam H,
      Stopper V, Lewis R, and Mills T. Nature Medicine 7: 119-122, 2001) showed that
      inhibition of Rho-kinase increased the erectile response (intracavernosal
      pressure and mean arterial pressure) by a process that does not require nitric
      oxide or cGMP. The present study investigated whether vasoconstrictor agents,
      which are active in the penis, act via the Rho-kinase pathway. Western analysis
      revealed RhoA and Rho-kinase protein in the penis. Treatment with the selective
      Rho-kinase inhibitor Y-27632 significantly increased the magnitude of the
      erectile response. Intracavernous administration of endothelin-1 (ET-1; 50 pmol)
      or methoxamine (10 microg/kg) reduced the erectile response to autonomic
      stimulation. If Y-27632 was given before ET-1 or methoxamine, the vasoconstrictor
      effect was reduced, and intracavernosal pressure and mean arterial pressure
      remained elevated. However, when given after methoxamine, Y-27632 had a reduced
      vasodilatory effect, and Y-27632 had no vasodilatory effect when given after ET
      1. These findings suggest that ET-1 and methoxamine increase Rho-kinase activity
      in the cavernous circulation and support the hypothesis that the vasoconstriction
      that maintains the penis in the nonerect state is mediated, in part, by the Rho
      kinase pathway.

PMID- 11509526
TI  - New method of cardiac output measurement using ultrasound velocity dilution in
      rats.
AB  - The aim of this study was to validate a new technique for the measurement of
      cardiac output (CO) based on ultrasound and dilution (COUD) in anesthetized rats.
      A transit time ultrasound (TTU) probe was placed around the rat carotid artery,
      and ultrasound velocity dilution curves were generated on intravenous injections
      of saline. CO by COUD were calculated from the dilution curves for normal and
      portal hypertensive rats in which CO was known to be increased. COUD was compared
      with the radiolabeled microsphere method and with direct aortic TTU flowmetry for
      baseline CO and drug-induced CO variations. CO in direct aortic TTU flowmetry was
      the ascending aorta blood flow measured directly by TTU probe (normal use of TTU
      flowmetry). The reproducibility of COUD within the same animal was also
      determined under baseline conditions. COUD detected the known CO increase in
      portal hypertensive rats compared with normal rats. CO values by COUD were
      correlated with those provided by microsphere technique or direct aortic TTU
      flowmetry (adjusted r = 0.76, P < 10(-4) and r = 0.79, P < 0.05, respectively).
      Baseline CO values and terlipressin-induced CO variations were detected by COUD
      and the other techniques. Intra- and interobserver agreements for COUD were
      excellent (intraclass r = 0.99 and 0.98, respectively). COUD was reproducible at
      least 10 times in 20 min. COUD is an accurate and reproducible method providing
      low-cost, repetitive CO measurements without open-chest surgery. It can be used
      in rats as an alternative to the microsphere method and to direct aortic
      flowmetry.

PMID- 11509527
TI  - Exercise training alters the effect of chronic hypoxia on myocardial adrenergic
      and muscarinic receptor number.
AB  - Chronic hypoxic exposure results in elevated sympathetic activity leading to
      downregulation of myocardial alpha(1)- and beta-adrenoceptors (alpha(1)-AR, beta
      AR). On the other hand, it has been shown that sympathetic activity is reduced by
      exercise training. The objective of this study was to determine whether exercise
      training could modify the changes in receptor expression associated with
      acclimatization. Four groups of rats were studied: normoxic sedentary rats (NS),
      rats living and training in normoxia (NTN), sedentary rats living in hypoxia (HS,
      inspired PO(2) = 110 Torr), and rats living and training in hypoxia (HTH,
      inspired PO(2) = 110 Torr). Training consisted of running in a treadmill at 80%
      of maximal O(2) uptake during 10 wk. Myocardial receptor density was measured by
      radioactive ligand binding. Right ventricular (RV) hypertrophy occurred in HS but
      not in HTH. No effect of exercise was detected in RV weight of normoxic rats.
      Acclimatization to hypoxia (HS vs. NS) resulted in a decrease in both alpha(1)-
      and beta-AR density, whereas muscarinic receptor (M-Ach) expression increased.
      Hypoxic exercise training (HS vs. HTH) moderated beta-AR downregulation and M-Ach
      upregulation and prevented the fall in alpha(1)-AR density. Normoxic training (NS
      vs. NTN) did not change beta-AR density. On the other hand, densities of alpha(1)
      AR in both ventricles as well as RV M-Ach increased in NTN vs. NS. The data show
      that exercise training in hypoxia 1) prevents RV hypertrophy, 2) suppresses the
      downregulation of alpha(1)-AR in the left ventricle (LV) and RV, and 3)
      attenuates the changes in both beta-AR and M-Ach receptor density in LV and RV.
      Exercise training in normoxia increases M-Ach receptor expression in the RV.

PMID- 11509528
TI  - Genetic selection of mice for high voluntary wheel running: effect on skeletal
      muscle glucose uptake.
AB  - Effects of genetic selection for high wheel-running activity (17th generation)
      and access to running wheels on skeletal muscle glucose uptake were studied in
      mice with the following treatments for 8 wk: 1) access to unlocked wheels; 2)
      same as 1, but wheels locked 48 h before glucose uptake measurement; or 3) wheels
      always locked. Selected mice ran more than random-bred (nonselected) mice (8-wk
      mean +/- SE = 8,243 +/- 711 vs. 3,719 +/- 233 revolutions/day). Body weight was 5
      13% lower for selected vs. nonselected groups. Fat pad/body weight was ~40% lower
      for selected vs. nonselected and unlocked vs. locked groups. Insulin-stimulated
      glucose uptake and fat pad/body weight were inversely correlated for isolated
      soleus (r = -0.333; P < 0.005) but not extensor digitorum longus (EDL) or
      epitrochlearis muscles. Insulin-stimulated glucose uptake was higher in EDL (P <
      0.02) for selected vs. nonselected mice. Glucose uptake did not differ by wheel
      group, and amount of running did not correlate with glucose uptake for any
      muscle. Wheel running by mice did not enhance subsequent glucose uptake by
      isolated muscles.

PMID- 11509530
TI  - Muscle activity in the leg is tuned in response to ground reaction forces.
AB  - During walking and running, the human body reacts to its external environment.
      One such response is to the impact forces that occur at heel strike. This study
      tested previous speculation that the levels of muscle activity in the lower
      extremities are adjusted in response to the loading rate of the impact forces. A
      pendulum apparatus was used to deliver repetitive impacts to the heels of 20
      subjects. Impact forces were of similar magnitude to those experienced during
      running, but the loading rate was varied by 13% using different materials in the
      subjects' shoes. Myoelectric patterns were measured in the tibialis anterior,
      medial gastrocnemius, vastus medialis, and biceps femoris muscles. Wavelet
      analysis was used to resolve intensity of the myoelectric patterns into time and
      frequency space. Substantial and significant differences in the myoelectric
      activity occurred between the impact conditions for the 50 ms before and the 50
      ms after impact, reaching 3 ms in timing, 16% in wavelet number, and 154% in the
      intensity of the muscle activity.

PMID- 11509529
TI  - Mortality after carotid body denervation in rats.
AB  - Carotid body denervation (CBD) in neonatal goats and piglets results in minimal
      irregular breathing and no fatalities. Redundancy and/or plasticity of peripheral
      chemosensitivity and a relatively mature ventilatory control system at birth may
      contribute to the paucity of CBD effects in these species. In the present study,
      we tested the hypothesis that CBD mortality would be greater in neonates of a
      less mature species such as the rat. We found that the mortality in rats
      denervated at 2-3 and 7-8 days of age was significantly higher (P < 0.05) than in
      sham-CBD rats. In all surviving rats, pulmonary ventilation during hypoxia was
      lower in CBD than in sham operated rats 2 days after denervation. In surviving
      rats denervated during the 7th and 8th postnatal days, there was also reduced
      weight gain and pulmonary ventilation during eupnea, including apneas up to 20 s
      in duration. However, the effects of CBD were compensated within 3 wk after
      denervation. Local injections of NaCN indicated that aortic chemoreceptors might
      have been one of the sites of recovery of peripheral chemosensitivity. We
      concluded that CBD has higher mortality in newborn rats than in other mammals,
      possibly because of the relative immaturity of these animals at birth.
      Nonetheless, in survivors there was enough redundancy and plasticity in the
      control of breathing to eventually compensate for the consequences of CBD.

PMID- 11509531
TI  - Effects of human eosinophil granule-derived cationic proteins on C-fiber
      afferents in the rat lung.
AB  - Experiments were performed to test the hypothesis that human eosinophil granule
      derived cationic proteins stimulate vagal C-fiber afferents in the lungs and
      elicit pulmonary chemoreflex responses in anesthetized Sprague-Dawley rats.
      Intratracheal instillation of eosinophil cationic protein (ECP; 1-2 mg/ml, 0.1
      ml) consistently induced an irregular breathing pattern, characterized by
      tachypnea (change in breathing frequency of 44.7%) and small unstable tidal
      volume (VT). The tachypnea, accompanied by decreased heart rate and arterial
      blood pressure, started within 30 s after the delivery of ECP and lasted for >30
      min. These ECP-induced cardiorespiratory responses were completely prevented by
      perineural capsaicin treatment of both cervical vagi, which selectively blocked C
      fiber conduction, suggesting the involvement of these afferents. Indeed, direct
      recording of single-unit activities of pulmonary C-fibers further demonstrated
      that the same dose of ECP evoked a pronounced and sustained (>30-min) stimulatory
      effect on pulmonary C-fibers. Furthermore, the sensitivity of these afferents to
      lung inflation was also markedly elevated after the ECP instillation, whereas the
      vehicle of ECP administered in the same manner had no effect. Other types of
      eosinophil granule cationic proteins, such as major basic protein and eosinophil
      peroxidase, induced very similar respiratory and cardiovascular reflex responses.
      In conclusion, these results show that eosinophil granule-derived cationic
      proteins induce a distinct stimulatory effect on vagal pulmonary C-fiber endings,
      which may play an important role in the airway hyperresponsiveness associated
      with eosinophil infiltration in the airways.

PMID- 11509532
TI  - Humidity does not affect central nervous system oxygen toxicity.
AB  - Central nervous system (CNS) oxygen toxicity can occur as convulsions and loss of
      consciousness when hyperbaric oxygen is breathed in diving and hyperbaric medical
      therapy. Lin and Jamieson (J Appl Physiol 75: 1980-1983, 1993) reported that
      humidity in the inspired gas enhances CNS oxygen toxicity. Because alveolar gas
      is fully saturated with water vapor, we could not see a cause and effect and
      surmised that other factors, such as metabolic rate, might be involved. Rats were
      exposed to 507- and 608-kPa O(2) in dry (31 or 14%) or humid (99%) atmosphere
      until the appearance of the first electrical discharge preceding the clinical
      convulsions. Each rat served as its own control. A thermoneutral temperature (28
      +/- 0.4 degrees C) yielded resting CO(2) production of 0.81 +/- 0.06 ml x g(-1) x
      h(-1). Latency to the first electrical discharge was not affected by humidity. At
      507-kPa O(2), latency was 23 +/- 0.4 and 22 +/- 0.7 min in dry and humid
      conditions, respectively, and, at 608-kPa O(2), latency was 15 +/- 4 and 14 +/- 3
      min in dry and humid conditions, respectively. When no effects of CO(2) and
      metabolic rate are present, humidity does not affect CNS oxygen toxicity.
      Relevance of the findings to diving and hyperbaric therapy is discussed.

PMID- 11509533
TI  - Evidence of LPL gene-exercise interaction for body fat and LPL activity: the
      HERITAGE Family Study.
AB  - Evidence of a gene-exercise interaction for traits related to body composition is
      limited. Here, the association between the lipoprotein lipase (LPL) S447X
      polymorphism and changes in body mass index, fat mass, percent body fat,
      abdominal visceral fat measured by computed tomography, and post-heparin plasma
      LPL activity in response to 20 wk of endurance training was investigated in 741
      adult white and black subjects. Changes were compared between carriers and
      noncarriers of the X447 allele after adjustment for the effects of age and
      pretraining values. No evidence of association was observed in men. However,
      white women carrying the X447 allele exhibited greater reductions of body mass
      index (P = 0.01), fat mass (P = 0.01), and percent body fat (P = 0.03); in black
      women, the carriers exhibited a greater reduction of abdominal visceral fat (P =
      0.05) and a greater increase in post-heparin LPL activity (P = 0.02). These
      results suggest that the LPL S447X polymorphism influences the training-induced
      changes in body fat and post-heparin LPL activity in women but not in men.

PMID- 11509534
TI  - Normalized force, activation, and coactivation in the arm muscles of young and
      old men.
AB  - The purpose of this study was to determine whether the loss of muscle strength in
      the elderly could be explained entirely by a decline in the physiological cross
      sectional area (PCSA) of muscle. Isometric force, muscle activation (twitch
      interpolation), and coactivation (surface electromyograph) were measured during
      maximal voluntary contractions (MVCs) of the elbow flexors (EFs) and extensors
      (EEs) in 20 young (23 +/- 3 yr) and 13 older (81 +/- 6 yr) healthy men. PCSA was
      determined using magnetic resonance imaging, and normalized force (NF) was
      calculated as the MVC/PCSA ratio. The PCSA was smaller in the old compared with
      the young men, more so in the EEs (28%) compared with the EFs (19%) (P < 0.001);
      however, the decline in MVC (approximately 30%) with age was similar in the two
      muscle groups. Muscle activation was not different between the groups, but
      coactivation was greater (5%) (P < 0.001) in the old men for both muscles. NF was
      less (11%) in the EFs (P < 0.01) and tended to be unchanged in the EEs of the old
      compared with young subjects. The relative maintenance of NF in the EEs compared
      with the EFs may be related to age-associated changes in the architecture of the
      triceps brachii muscle. In conclusion, although the decline in PCSA explained the
      majority of strength loss in the old men, additional factors such as greater
      coactivation or reduced specific tension also may have contributed to the age
      related loss of isometric strength.

PMID- 11509535
TI  - beta(1)-Subunit of BK channels regulates arterial wall[Ca(2+)] and diameter in
      mouse cerebral arteries.
AB  - Mice with a disrupted beta(1) (BK beta(1))-subunit of the large-conductance
      Ca(2+)-activated K(+) (BK) channel gene develop systemic hypertension and cardiac
      hypertrophy, which is likely caused by uncoupling of Ca(2+) sparks to BK channels
      in arterial smooth muscle cells. However, little is known about the physiological
      levels of global intracellular Ca(2+) concentration ([Ca(2+)](i)) and its
      regulation by Ca(2+) sparks and BK channel subunits. We utilized a BK beta(1)
      knockout C57BL/6 mouse model and studied the effects of inhibitors of ryanodine
      receptor and BK channels on the global [Ca(2+)](i) and diameter of small cerebral
      arteries pressurized to 60 mmHg. Ryanodine (10 microM) or iberiotoxin (100 nM)
      increased [Ca(2+)](i) by approximately 75 nM and constricted +/+ BK beta(1) wild
      type arteries (pressurized to 60 mmHg) with myogenic tone by approximately 10
      microm. In contrast, ryanodine (10 microM) or iberiotoxin (100 nM) had no
      significant effect on [Ca(2+)](i) and diameter of -/- BK beta(1)-pressurized (60
      mmHg) arteries. These results are consistent with the idea that Ca(2+) sparks in
      arterial smooth muscle cells limit myogenic tone through activation of BK
      channels. The activation of BK channels by Ca(2+) sparks reduces the voltage
      dependent Ca(2+) influx and [Ca(2+)](i) through tonic hyperpolarization. Deletion
      of BK beta(1) disrupts this negative feedback mechanism, leading to increased
      arterial tone through an increase in global [Ca(2+)](i).

PMID- 11509536
TI  - Angiotensin-converting enzyme genotype and physical performance during US Army
      basic training.
AB  - Prior studies have suggested that angiotensin I-converting enzyme (ACE) genotype
      correlates with superior physical performance in highly selected populations.
      This study assessed whether such an association exists in a heterogeneous
      population. Using polymerase chain reaction techniques, we determined the ACE
      genotypes (insertion/insertion, deletion/insertion, or deletion/deletion) of 62
      male and 85 female US Army recruits. Before and after 8 wk of basic training, we
      determined peak oxygen uptake and performance on the Army Physical Fitness Test
      (APFT), which includes standardized measures of muscular endurance (sit-ups, push
      ups) and a 2-mile run. Subjects of different ACE genotypes had similar peak
      oxygen uptakes and APFT scores, both before and after training. Subjects with
      genotype II had higher APFT scores than others, but the differences were not
      statistically significant. Furthermore, no ACE genotype group had a performance
      advantage in analyses that adjusted for baseline fitness. We conclude that ACE
      genotype does not have a strong effect on aerobic power or muscular endurance in
      healthy, young American adults drawn from an ethnically and geographically
      diverse population.

PMID- 11509537
TI  - Total weak acid concentration and effective dissociation constant of nonvolatile
      buffers in human plasma.
AB  - The strong ion approach provides a quantitative physicochemical method for
      describing the mechanism for an acid-base disturbance. The approach requires
      species-specific values for the total concentration of plasma nonvolatile buffers
      (A(tot)) and the effective dissociation constant for plasma nonvolatile buffers
      (K(a)), but these values have not been determined for human plasma. Accordingly,
      the purpose of this study was to calculate accurate A(tot) and K(a) values using
      data obtained from in vitro strong ion titration and CO(2) tonometry. The
      calculated values for A(tot) (24.1 mmol/l) and K(a) (1.05 x 10(-7)) were
      significantly (P < 0.05) different from the experimentally determined values for
      horse plasma and differed from the empirically assumed values for human plasma
      (A(tot) = 19.0 meq/l and K(a) = 3.0 x 10(-7)). The derivatives of pH with respect
      to the three independent variables [strong ion difference (SID), PCO(2), and
      A(tot)] of the strong ion approach were calculated as follows: dpH/dSID(+) = [1 +
      10(pK(a)-pH)](2)/(2.303 x [SPCO(2)10(pH-pK'(1)[1 + 10(pK(a)-pH](2) +
      A(tot)10(pK(a)-PH]]; dpH/dPCO(2) = S10(-pK'(1)/[2.303[A(tot)10(pH)(10(pH +
      10(pK(a))(-2) - SID(+)10(-pH)]], dpH/dA(tot) = -1/[2.303[SPCO(2)10(pH-pK'(1) +
      SID(+)10(pK(a)-pH)]], where S is solubility of CO(2) in plasma. The derivatives
      provide a useful method for calculating the effect of independent changes in
      SID(+), PCO(2), and A(tot) on plasma pH. The calculated values for A(tot) and
      K(a) should facilitate application of the strong ion approach to acid-base
      disturbances in humans.

PMID- 11509538
TI  - Tryptase and agonists of PAR-2 induce the proliferation of human airway smooth
      muscle cells.
AB  - Airway remodeling with smooth muscle cell (SMC) hyperplasia is a feature of
      chronic asthma. We investigated the potential for tryptase, the major secretory
      product of human mast cells, to act as a growth factor for human airway SMCs.
      Because this serine protease can activate proteinase-activated receptor-2 (PAR
      2), we also examined the actions of SLIGKV, a peptide agonist of PAR-2.
      Incubation with lung tryptase provoked a twofold increase in [(3)H]thymidine
      incorporation; a similar increase in cell numbers was found when we used the MTS
      assay. The effect was catalytic site dependent, being abolished by the protease
      inhibitors leupeptin and benzamidine and by heat inactivation of the enzyme.
      Tryptase-induced DNA synthesis was inhibited by preincubation of the cells with
      pertussis toxin, calphostin C, or genistein. Transduction mechanisms are thus
      likely to involve a pertussis toxin-sensitive G protein, protein kinase C, and
      tyrosine kinase. SLIGKV elicited a response on SMCs similar to that of tryptase.
      Tryptase could provide an important stimulus for SMC proliferation in asthmatic
      airways, by acting on PAR-2.

PMID- 11509539
TI  - Mechanism of inhibition of matrix metalloproteinase-9 induction by NO in vascular
      smooth muscle cells.
AB  - Vascular smooth muscle (VSM) cell migration is a critical step in the development
      of a neointima after angioplasty. Matrix metalloproteinases (MMPs) degrade the
      basement membrane and extracellular matrix, facilitating VSM cell migration.
      Recently, we demonstrated that nitric oxide (NO) inhibits interleukin-1 beta (IL
      1 beta)-stimulated MMP-9 induction in rat aortic VSM cells. In this study, we
      examined the hypothesis that NO inhibits MMP-9 induction by attenuating
      superoxide generation and extracellular signal-regulated kinase (ERK) activation.
      Stimulation of VSM cells with IL-1 beta significantly (P < 0.05) increased
      superoxide production, ERK activation, and MMP-9 induction. Pretreatment of VSM
      cells with the NO donor DETA NONOate significantly (P < 0.05) decreased IL-1 beta
      stimulated superoxide generation. In addition, pretreatment of VSM cells with a
      specific ERK pathway inhibitor, PD-98059, or DETA NONOate inhibited IL-1 beta
      stimulated ERK activation and MMP-9 induction. Direct exposure of VSM cells to
      increased superoxide levels by treatment with xanthine/xanthine oxidase increased
      ERK activation and MMP-9 induction, whereas pretreatment of cells with PD-98059
      significantly (P < 0.05) inhibited xanthine/xanthine oxidase-stimulated ERK
      activation and MMP-9 induction. We conclude that NO inhibits IL-1 beta-stimulated
      MMP-9 induction by inhibiting superoxide generation and subsequent ERK
      activation.

PMID- 11509540
TI  - Distribution and colocalization of neurotransmitters and receptors in the pre
      Botzinger complex of rats.
AB  - The pre-Botzinger complex (PBC), thought to be the center of respiratory rhythm
      generation, is a cell column ventrolateral to the nucleus ambiguus. The present
      study analyzed its cellular and neurochemical composition in adult rats. PBC
      neurons were mainly oval, fusiform, or multipolar in shape and small to medium in
      size. Neurokinin-1 receptor, a marker of the PBC, was present in the plasma
      membrane of mostly medium and small neurons and their associated processes and
      boutons. Among neurons immunoreactive for different neurotransmitter or receptor
      candidates, various numbers were colocalized with neurokinin-1 receptor. The
      highest ratio was with nitric oxide synthase (52.72%), and the lowest was with
      glycine receptors (31.93%). Glutamic acid decarboxylase- and glycine transporter
      2-immunoreactive boutons, as well as GABA(A) receptor-immunoreactive plasma
      membrane processes and boutons, were also identified in the PBC. PBC neurons
      exhibited different levels of cytochrome oxidase activity, indicating their
      various energy demands. Our results suggest that synaptic interactions within the
      PBC of adult rats involve a variety of neurotransmitter and receptor types and
      that nitric oxide may play an important role in addition to glutamate, GABA,
      glycine, and neurokinin.

PMID- 11509541
TI  - Efficacy of nasal strip and furosemide in mitigating EIPH in Thoroughbred horses.
AB  - The purpose of this investigation was to study the effects of an equine nasal
      strip (NS), furosemide (Fur), and a combination of both (NS + Fur) on exercise
      induced pulmonary hemorrhage (EIPH) at speeds corresponding to near-maximal
      effort. Five Thoroughbreds (526 +/- 25 kg) were run on a flat treadmill from 7 to
      14 m/s in 1 m x s(-1) x min(-)1 increments every 2 wk (treatment order
      randomized) under control (Con), Fur (1 mg/kg iv 4 h prior), NS, or NS + Fur
      conditions. During each run, pulmonary arterial (Ppa) and esophageal (Pes)
      pressures were measured. Severity of EIPH was quantified via bronchoalveolar
      lavage (BAL) 30 min postrun. Furosemide (Fur and NS + Fur trials) reduced peak
      Ppa approximately 7 mmHg compared with Con (P < 0.05) whereas NS had no effect (P
      > 0.05). Maximal Pes swings were not different among groups (P > 0.05). NS
      significantly diminished EIPH compared with the Con trial [Con, 55.0 +/- 36.2;
      NS, 30.8 +/- 21.8 x 10(6) red blood cells (RBC)/ml BAL fluid; P < 0.05]. Fur
      reduced EIPH to a greater extent than NS (5.2 +/- 3.0 x 10(6) RBC/ml BAL; P <
      0.05 vs. Con and NS) with no additional benefit from NS + Fur (8.5 +/- 4.2 x
      10(6) RBC/ml BAL; P > 0.05 vs. Fur, P < 0.05 vs. Con and NS). In conclusion,
      although both modalities (NS and Fur) were successful in mitigating EIPH, neither
      abolished EIPH fully as evaluated via BAL. Fur was more effective than NS in
      constraining the severity of EIPH. The simultaneous use of both interventions
      appears to offer no further gain with respect to reducing EIPH.

PMID- 11509542
TI  - Regulation of vocal fold transepithelial water fluxes.
AB  - Vocal fold hydration is critical to phonation. We hypothesized that the vocal
      fold generates bidirectional water fluxes, which are regulated by activity of the
      Na(+)-K(+)- ATPase. Western blots and immunohistochemistry demonstrated the
      presence of the alpha-subunit Na(+)-K(+)-ATPase in the canine vocal fold (n =
      11). Luminal cells, basal and adjacent one to two layers of suprabasal cells
      within stratified squamous epithelium, were immunopositive, as well as
      basolateral membranes of submucosal seromucous glands underlying transitional
      epithelia. Canine (n = 6) and ovine (n = 14) vocal fold mucosae exhibited
      transepithelial potential differences of 8.1 +/- 2.8 and 9.3 +/- 1.3 mV (lumen
      negative), respectively. The potential difference and short-circuit current
      (ovine = 31 +/- 4 microA/cm(2); canine = 41 +/- 10 microA/cm(2)) were
      substantially reduced by luminal administration of 75 microM acetylstrophanthidin
      (P < 0.05). Ovine (n = 7) transepithelial water fluxes decreased from 5.1 +/- 0.3
      to 4.3 +/- 0.3 microl x min(-1) x cm(-2) from the basal to luminal chamber and
      from 5.2 +/- 0.2 to 3.9 +/- 0.3 microl x min(-1) x cm(-2) from the luminal to
      basal chamber by luminal acetylstrophanthidin (P < 0.05). The presence of the
      Na(+)-K(+)-ATPase in the vocal fold epithelium and the electrolyte transport
      derived from its activity provide the intrinsic mechanisms to regulate cell
      volume as well as vocal fold hydration.

PMID- 11509543
TI  - Activation of MAPK by modified low-density lipoproteins in vascular smooth muscle
      cells.
AB  - A high concentration of circulating low-density lipoproteins (LDL) is a major
      risk factor for atherosclerosis. Native LDL and LDL modified by glycation and/or
      oxidation are increased in diabetic individuals. LDL directly stimulate vascular
      smooth muscle cell (VSMC) proliferation; however, the mechanisms remain
      undefined. The extracellular signal-regulated kinase (ERK) pathway mediates
      changes in cell function and growth. Therefore, we examined the cellular effects
      of native and modified LDL on ERK phosphorylation in VSMC. Addition of native,
      mildly modified (oxidized, glycated, glycoxidized) and highly modified (highly
      oxidized, highly glycoxidized) LDL at 25 microg/ml to rat VSMC for 5 min induced
      a fivefold increase in ERK phosphorylation. To elucidate the signal transduction
      pathway by which LDL phosphorylate ERK, we examined the roles of the
      Ca(2+)/calmodulin pathway, protein kinase C (PKC), src kinase, and mitogen
      activated protein kinase kinase (MEK). Treatment of VSMC with the intracellular
      Ca(2+) chelator EGTA-AM (50 micromol/l) significantly increased ERK
      phosphorylation induced by native and mildly modified LDL, whereas chelation of
      extracellular Ca(2+) by EGTA (3 mmol/l) significantly reduced LDL-induced ERK
      phosphorylation. The calmodulin inhibitor N-(6-aminohexyl)-1
      naphthalenesulfonamide (40 micromol/l) significantly decreased ERK
      phosphorylation induced by all types of LDL. Downregulation of PKC with phorbol
      myristate acetate (5 micromol/l) markedly reduced LDL-induced ERK
      phosphorylation. Pretreatment of VSMC with a cell-permeable MEK inhibitor (PD
      98059, 40 micromol/l) significantly decreased ERK phosphorylation in response to
      native and modified LDL. These findings indicate that native and mildly and
      highly modified LDL utilize similar signaling pathways to phosphorylate ERK and
      implicate a role for Ca(2+)/calmodulin, PKC, and MEK. These results suggest a
      potential link between modified LDL, vascular function, and the development of
      atherosclerosis in diabetes.

PMID- 11509544
TI  - Invited review: cGMP-dependent protein kinase signaling mechanisms in smooth
      muscle: from the regulation of tone to gene expression.
AB  - cGMP is a second messenger that produces its effects by interacting with
      intracellular receptor proteins. In smooth muscle cells, one of the major
      receptors for cGMP is the serine/threonine protein kinase, cGMP-dependent protein
      kinase (PKG). PKG has been shown to catalyze the phosphorylation of a number of
      physiologically relevant proteins whose function it is to regulate the
      contractile activity of the smooth muscle cell. These include proteins that
      regulate free intracellular calcium levels, the cytoskeleton, and the
      phosphorylation state of the regulatory light chain of smooth muscle myosin.
      Other studies have shown that vascular smooth muscle cells (VSMCs) that are
      cultured in vitro may cease to express PKG and will, coincidentally, acquire a
      noncontractile, synthetic phenotype. The restoration of PKG expression to the
      synthetic phenotype VSMC results in the cells acquiring a more contractile
      phenotype. These more recent studies suggest that PKG controls VSMC gene
      expression that, in turn, regulates phenotypic modulation of the cells.
      Therefore, the regulation of PKG gene expression appears to be linked to
      phenotypic modulation of VSMC. Because several vascular disorders are related to
      the accumulation of synthetic, fibroproliferative VSMC in the vessel wall, it is
      likely that changes in the activity of the nitric oxide/cGMP/PKG pathway is
      involved the development of these diseases.

PMID- 11509545
TI  - Invited review: the circle of life: cell cycle regulation in airway smooth
      muscle.
AB  - Severe asthma is characterized by increased airway smooth muscle (ASM) mass, due
      predominantly to ASM hyperplasia. Diverse stimuli, which include growth factors,
      plasma- or inflammatory cell-derived mediators, contractile agonists, cytokines,
      and extracellular matrix proteins, induce ASM proliferation. Mitogens act via
      receptor tyrosine kinase, G protein-coupled receptors, or cytokine receptors, to
      activate p21ras and stimulate two parallel signaling pathways in ASM cells,
      namely, the extracellular signal-regulated kinase (ERK) or the
      phosphatidylinositol 3-kinase (PI3K) pathways. ERK and PI3K regulate cell cycle
      protein expression and thus modulate cell cycle traversal. ERK activation and
      downstream effectors of PI3K, such as Rac1 and Cdc42, stimulate expression of
      cyclin D1, a key regulator of G(1) progression in the mammalian cell cycle. In
      addition, PI3K activates 70-kDa ribosomal S6 kinase, an enzyme that also
      regulates the translation of many cell cycle proteins, including the elongation
      factor E2F. The present review examines the mitogens and critical signal
      transduction pathways that stimulate ASM cell proliferation. Further study in
      this area may reveal new therapeutic targets to abrogate ASM hyperplasia in
      diseases such as asthma and chronic obstructive pulmonary disease.

PMID- 11509546
TI  - Invited review: mechanisms of calcium handling in smooth muscles.
AB  - The concentration of cytoplasmic Ca(2+) regulates the contractile state of smooth
      muscle cells and tissues. Elevations in global cytoplasmic Ca(2+) resulting in
      contraction are accomplished by Ca(2+) entry and release from intracellular
      stores. Pathways for Ca(2+) entry include dihydropyridine-sensitive and 
      insensitive Ca(2+) channels and receptor and store-operated nonselective channels
      permeable to Ca(2+). Intracellular release from the sarcoplasmic reticulum (SR)
      is accomplished by ryanodine and inositol trisphosphate receptors. The impact of
      Ca(2+) entry and release on cytoplasmic concentration is modulated by Ca(2+)
      reuptake into the SR, uptake into mitochondria, and extrusion into the
      extracellular solution. Highly localized Ca(2+) transients (i.e., sparks and
      puffs) regulate ionic conductances in the plasma membrane, which can provide
      feedback to cell excitability and affect Ca(2+) entry. This short review
      describes the major transport mechanisms and compartments that are utilized for
      Ca(2+) handling in smooth muscles.

PMID- 11509548
TI  - Selected contribution: roles of focal adhesion kinase and paxillin in the
      mechanosensitive regulation of myosin phosphorylation in smooth muscle.
AB  - The increase in intracellular Ca(2+) and myosin light chain (MLC) phosphorylation
      in response to the contractile activation of tracheal smooth muscle is greater at
      longer muscle lengths (21). However, MLC phosphorylation can also be stimulated
      by Ca(2+)-insensitive signaling pathways (19). The cytoskeletal proteins paxillin
      and focal adhesion kinase (FAK) mediate a Ca(2+)-independent length-sensitive
      signaling pathway in tracheal smooth muscle (30). We used alpha-toxin
      permeabilized tracheal smooth muscle strips to determine whether the length
      sensitivity of MLC phosphorylation can be regulated by a Ca(2+)-insensitive
      signaling pathway and whether the length sensitivity of active tension depends on
      the length sensitivity of myosin activation. Although active tension remained
      length sensitive, ACh-induced MLC phosphorylation was the same at optimal muscle
      length (L(o)) and 0.5 L(o) when intracellular Ca(2+) was maintained at pCa 7. MLC
      phosphorylation was also the same at L(o) and 0.5 L(o) in strips stimulated with
      10 microM Ca(2+). In contrast, the Ca(2+)-insensitive tyrosine phosphorylation of
      FAK and paxillin stimulated by ACh was higher at L(o) than at 0.5 L(o). We
      conclude that the length-sensitivity of MLC phosphorylation depends on length
      dependent changes in intracellular Ca(2+) but that length-dependent changes in
      MLC phosphorylation are not the primary mechanism for the length sensitivity of
      active tension.

PMID- 11509549
TI  - Selected contribution: HSP20 phosphorylation in nitroglycerin- and forskolin
      induced sustained reductions in swine carotid media tone.
AB  - Cyclic nucleotide-induced relaxation of maximally activated arterial smooth
      muscle has two phases. 1) The initial relaxation transient is typically
      characterized by a rapid reduction in force associated with brief reductions in
      myoplasmic Ca(2+) concentration ([Ca(2+)](i)) and myosin regulatory light chain
      (MRLC) phosphorylation on serine (Ser)-19 (Ser(19)). 2) The sustained inhibitory
      response is typically associated with Ser(16) phosphorylation of heat shock
      protein 20 (HSP20) without sustained reductions in [Ca(2+)](i) or MRLC
      phosphorylation. We investigated whether the extent of Ser(16)-HSP20
      phosphorylation quantitatively correlated with the sustained inhibitory response.
      With addition of nitroglycerin to histamine-stimulated swine carotid media, the
      initial relaxation transient was associated with a decrease in MRLC
      phosphorylation without an increase in Ser(16)-HSP20 phosphorylation. During the
      sustained phase of nitroglycerin-induced relaxation and during force
      redevelopment induced by washout of nitroglycerin in the continued presence of
      histamine, the level of Ser(16)-HSP20 phosphorylation, but not MRLC
      phosphorylation, correlated with inhibition of force. Forskolin, which increases
      cAMP concentration, also induced a sustained inhibitory response that was
      associated with increases in Ser(16)-HSP20 phosphorylation without reductions in
      MRLC phosphorylation levels. Forskolin increased Ser(16)-HSP20 phosphorylation to
      a greater extent and inhibited force more completely than that observed with
      nitroglycerin. Increases in Ser(16)-HSP20 phosphorylation correlated with the
      degree of force inhibition regardless of whether the relaxation was induced by
      nitroglycerin or forskolin. These data are consistent with the hypothesis that
      Ser(16)-HSP20 phosphorylation may be a cyclic nucleotide-dependent, yet MRLC
      phosphorylation-independent, inhibitor of smooth muscle contractile force.

PMID- 11509550
TI  - Selected contribution: synergism between TNF-alpha and IL-1 beta in airway smooth
      muscle cells: implications for beta-adrenergic responsiveness.
AB  - In human cultured airway smooth muscle cells, interleukin (IL)-1 beta increases
      cyclooxygenase (COX)-2 expression and PGE(2) release, ultimately resulting in
      decreased beta-adrenergic responsiveness. In this study, we aimed to determine
      whether tumor necrosis factor-alpha (TNF-alpha) synergizes with IL-1 beta in the
      induction of these events. TNF-alpha alone, at concentrations up to 10 ng/ml, had
      no effect on COX-2 protein expression; at concentrations as low as 0.1 ng/ml, it
      significantly enhanced the ability of IL-1 beta (0.2 ng/ml) to induce COX-2 and
      to increase PGE(2) release. IL-1 beta and TNF-alpha in combination also
      significantly enhanced COX-2 promoter activity, indicating that synergism between
      the cytokines is mediated at the level of gene transcription. Although IL-1 beta
      and TNF-alpha each increased nuclear factor-kappa B activation and induced
      extracellular regulated kinase and p38 phosphorylation, combined administration
      of the cytokines did not enhance either nuclear factor-kappa B or mitogen
      activated protein kinase activation. Combined administration of IL-1 beta (0.2
      ng/ml) and TNF-alpha (0.1 or 1.0 ng/ml) reduced the ability of isoproterenol to
      decrease human airway smooth muscle cell stiffness, as measured by magnetic
      twisting cytometry, even though individually these cytokines, at these
      concentrations, had no effect on isoproterenol responses. Treatment with the
      selective COX-2 inhibitor NS-398 abolished the synergistic effects of TNF-alpha
      and IL-1 beta on beta-adrenergic responsiveness. Our results indicate that low
      concentrations of IL-1 beta and TNF-alpha synergize to promote beta-adrenergic
      hyporesponsiveness and that effects on COX-2 expression and PGE(2) are
      responsible for these events. The data suggest that the simultaneous release in
      the airway, of even very small amounts of cytokines, can have important
      functional consequences.

PMID- 11509551
TI  - Selected contribution: insulin utilizes NO/cGMP pathway to activate myosin
      phosphatase via Rho inhibition in vascular smooth muscle.
AB  - Our laboratory has recently demonstrated that insulin induces relaxation of
      vascular smooth muscle cells (VSMCs) by activating myosin-bound phosphatase (MBP)
      and by inhibiting Rho kinase (Begum N, Duddy N, Sandu OA, Reinzie J, and Ragolia
      L. Mol Endocrinol 14: 1365-1376, 2000). In this study, we tested the hypothesis
      that insulin via the nitric oxide (NO)/cGMP pathway may inactivate Rho, resulting
      in a decrease in phosphorylation of the myosin-bound subunit (MBS(Thr695)) of MBP
      and in its activation. Treatment of confluent serum-starved VSMCs with insulin
      prevented thrombin-induced increases in membrane-associated RhoA, Rho kinase
      activation, and site-specific phosphorylation of MBS(Thr695) of MBP and caused
      MBP activation. Preexposure to N(G)-monomethyl-L-arginine, a NO synthase
      inhibitor, and R-p-8-(4-chlorophenylthio)cGMP, a cGMP antagonist, attenuated
      insulin's inhibitory effect on Rho translocation and restored thrombin-mediated
      Rho kinase activation and site-specific MBS(Thr695) phosphorylation, resulting in
      MBP inactivation. In contrast, 8-bromo-cGMP, a cGMP agonist, mimicked insulin's
      inhibitory effects by abolishing thrombin-mediated Rho signaling and promoted
      dephosphorylation of MBS(Thr695). Furthermore, expression of a dominant-negative
      RhoA decreased basal as well as thrombin-induced MBS(Thr695) phosphorylation and
      caused insulin activation of MBP. Collectively, these results indicate that
      insulin inhibits Rho signaling by decreasing RhoA translocation via the NO/cGMP
      signaling pathway to cause MBP activation via site-specific dephosphorylation of
      its regulatory subunit MBS.

PMID- 11509552
TI  - Backbone dynamics of plastocyanin in both oxidation states. Solution structure of
      the reduced form and comparison with the oxidized state.
AB  - A model-free analysis based on (15)N R(1), (15)N R(2), and (15)N-(1)H nuclear
      Overhauser effects was performed on reduced (diamagnetic) and oxidized
      (paramagnetic) forms of plastocyanin from Synechocystis sp. PCC6803. The protein
      backbone is rigid, displaying a small degree of mobility in the sub-nanosecond
      time scale. The loops surrounding the copper ion, involved in physiological
      electron transfer, feature a higher extent of flexibility in the longer time
      scale in both redox states, as measured from D(2)O exchange of amide protons and
      from NH-H(2)O saturation transfer experiments. In contrast to the situation for
      other electron transfer proteins, no significant difference in the dynamic
      properties is found between the two redox forms. A solution structure was also
      determined for the reduced plastocyanin and compared with the solution structure
      of the oxidized form in order to assess possible structural changes related to
      the copper ion redox state. Within the attained resolution, the structure of the
      reduced plastocyanin is indistinguishable from that of the oxidized form, even
      though small chemical shift differences are observed. The present
      characterization provides information on both the structural and dynamic behavior
      of blue copper proteins in solution that is useful to understand further the
      role(s) of protein dynamics in electron transfer processes.

PMID- 11509553
TI  - N-acetylcysteine induces cell cycle arrest in hepatic stellate cells through its
      reducing activity.
AB  - Activation of hepatic stellate cells (HSC) has been identified as a critical step
      in hepatic fibrogenesis and is regulated by several factors including cytokines
      and oxidative stress. However, the molecular mechanism for HSC inactivation is
      not well understood. We investigated an N-acetyl-L-cysteine (NAC)-mediated
      signaling pathway involved in HSC inactivation. NAC, which acting through its
      reducing activity, induced cell arrest at G1 via the mitogen-activated protein
      kinase (MAPK) kinase (MEK)/MAPK pathway in a Ras-independent manner. The
      sustained activation of this extracellular signal-regulated kinase induced the
      expression of p21(Cip1/WAF1), a cell cycle-dependent kinase inhibitor, and
      mediated cell growth arrest through the Sp1 transcription activator-dependent
      mechanism. These effects of NAC were all reversed by treatment of HSC with MEK
      inhibitor PD98059 followed by culturing HSC on type I collagen-coated flasks. The
      collagen-mediated suppression of NAC-induced arrest may be due to an overriding
      of the cell cycle arrest through an acceleration of integrin-induced cell growth.
      NAC action is actually dependent on modulating the redox states of cysteine
      residues of target proteins such as Raf-1, MEK, and ERK. In conclusion, an
      understanding of the NAC signaling pathway in HSC should provide the theoretical
      basis for clinical approaches using antioxidant therapies in liver fibrosis.

PMID- 11509554
TI  - Role of threonines in the Arabidopsis thaliana somatic embryogenesis receptor
      kinase 1 activation loop in phosphorylation.
AB  - The Arabidopsis thaliana somatic embryogenesis receptor kinase 1 (AtSERK1) gene
      encodes a receptor-like protein kinase that is transiently expressed during
      embryogenesis. To determine the intrinsic biochemical properties of the AtSERK1
      protein, we have expressed the intracellular catalytic domain as a glutathione S
      transferase fusion protein in Escherichia coli. The AtSERK1-glutathione S
      transferase fusion protein mainly autophosphorylates on threonine residues (K(m)
      for ATP, 4 x 10(-6) m), and the reaction is Mg(2+) dependent and inhibited by
      Mn(2+). A K330E substitution in the kinase domain of AtSERK1 abolishes all kinase
      activity. The active AtSERK1(kin) can phosphorylate inactive AtSERK1(K330E)
      protein, suggesting an intermolecular mechanism of autophosphorylation. The
      AtSERK1 kinase protein was modeled using the insulin receptor kinase as a
      template. On the basis of this model, threonine residues in the AtSERK1
      activation loop of catalytic subdomain VIII are potential targets for
      phosphorylation. AtSERK1 phosphorylation on myelin basic protein and casein
      showed tyrosine, serine, and threonine as targets, demonstrating that AtSERK1 is
      a dual specificity kinase. Replacing Thr-468 with either alanine or glutamic acid
      not only obliterated the ability of the AtSERK1 protein to be phosphorylated but
      also inhibited phosphorylation on myelin basic protein and casein, suggesting
      that Thr-468 is essential for AtSERK-mediated signaling.

PMID- 11509555
TI  - Synaptic scaffolding proteins in rat brain. Ankyrin repeats of the multidomain
      Shank protein family interact with the cytoskeletal protein alpha-fodrin.
AB  - The postsynaptic density is the ultrastructural entity containing the
      neurotransmitter reception apparatus of excitatory synapses in the brain. A
      recently identified family of multidomain proteins termed Src homology 3 domain
      and ankyrin repeat-containing (Shank), also known as proline-rich synapse
      associated protein/somatostatin receptor-interacting protein, plays a central
      role in organizing the subsynaptic scaffold by interacting with several synaptic
      proteins including the glutamate receptors. We used the N-terminal ankyrin
      repeats of Shank1 and -3 to search for interacting proteins by yeast two-hybrid
      screening and by affinity chromatography. By cDNA sequencing and mass
      spectrometry the cytoskeletal protein alpha-fodrin was identified as an
      interacting molecule. The interaction was verified by pull-down assays and by
      coimmunoprecipitation experiments from transfected cells and brain extracts.
      Mapping of the interacting domains of alpha-fodrin revealed that the highly
      conserved spectrin repeat 21 is sufficient to bind to the ankyrin repeats. Both
      interacting partners are coexpressed widely in the rat brain and are colocalized
      in synapses of hippocampal cultures. Our data indicate that the Shank1 and -3
      family members provide multiple independent connections between synaptic
      glutamate receptor complexes and the cytoskeleton.

PMID- 11509556
TI  - Acetylation by histone acetyltransferase CREB-binding protein/p300 of STAT6 is
      required for transcriptional activation of the 15-lipoxygenase-1 gene.
AB  - Interleukin-4 (IL-4) induces expression of reticulocyte-type 15-lipoxygenase-1
      (15-LOX-1) in various mammalian cells via the Janus kinase/signal transducer and
      activator of transcription 6 (STAT6) signaling system. We studied the mechanism
      of 15-LOX-1 induction in A549 lung epithelial cells and found that genistein, a
      potent tyrosine kinase inhibitor, prevented phopsphorylation of STAT6, its
      binding to the 15-LOX-1 promoter, and the expression of catalytically active
      enzyme. In contrast, cycloheximide did not prevent 15-LOX-1 induction.
      Surprisingly, we found that IL-4 up-regulated the histone acetyltransferase
      activity of CREB-binding protein (CBP)/p300, which is responsible for acetylation
      of nuclear histones and STAT6. The acetylation of both proteins appears to be
      essential for the IL-4-induced signal transduction cascade, because inhibition of
      CBP/p300 by the viral wild-type E1A oncoprotein abrogated acetylation of both
      histones and STAT6 and strongly suppressed transcriptional activation of the 15
      LOX-1 gene. Moreover, we found that the inhibition by sodium butyrate of histone
      deacetylases, which apparently suppress 15-LOX-1 gene transcription,
      synergistically enhanced the IL-4-stimulated 15-LOX-1 expression. These data
      suggest that both phosphorylation and acetylation of STAT6 as well as acetylation
      of nuclear histones are involved in transcriptional activation of the 15-LOX-1
      gene, although these reactions follow differential kinetics. STAT6
      phosphorylation proceeds within the first hour of IL-4 stimulation. In contrast,
      CBP/p300-mediated acetylation requires 9-11 h, and similar kinetics were observed
      for the expression of the active enzyme. Thus, our results suggest that in the
      absence of IL-4, nuclear histones may be bound to regulatory elements of the 15
      LOX-1 gene, preventing its transcription. IL-4 stimulation causes rapid
      phosphorylation of STAT6, but its binding to the promoter appears to be prevented
      by nonacetylated histones. After 9-11 h, when histones become acetylated, STAT6
      binding sites may be demasked so that the phosphorylated and acetylated
      transcription factor can bind to activate gene transcription.

PMID- 11509557
TI  - Insulin-like growth factor-I induces renal cell hypertrophy via a calcineurin
      dependent mechanism.
AB  - Insulin-like growth factor-I (IGF-I) may play an important role in the
      development of renal hypertrophy. In this study we determined the effect of IGF-I
      on cultured mesangial cells (MCs) and examined activation of key signaling
      pathways. IGF-I induced hypertrophy as determined by an increase in cell size and
      an increase in protein to DNA ratio and increased accumulation of extracellular
      matrix (ECM) proteins. IGF-I also activated both Erk1/Erk2 MAPK and
      phosphatidylinositol 3-kinase (PI3K) in MCs. Inhibition of either MAPK or PI3K,
      however, had no effect on IGF-I-induced hypertrophy or ECM production. Next, we
      examined the effect of IGF-I on activation of the calcium-dependent phosphatase
      calcineurin. IGF-I treatment stimulated calcineurin activity and increased the
      protein levels of calcineurin and the calcineurin binding protein, calmodulin.
      Cyclosporin A, an inhibitor of calcineurin, blocked both IGF-I-mediated
      hypertrophy and up-regulation of ECM. In addition, calcineurin resulted in
      sustained Akt activation, indicating possible cross-talk with other signaling
      pathways. Finally, IGF-I treatment resulted in the calcineurindependent nuclear
      localization of NFATc1. Therefore, IGF-I induces hypertrophy and increases ECM
      accumulation in MCs. IGF-I-mediated hypertrophy is associated with activation of
      Erk1/Erk2 MAPK and PI3K but does not require either of these pathways. Instead,
      IGF-I mediates hypertrophy via a calcineurin-dependent pathway.

PMID- 11509558
TI  - Nucleocytoplasmic shuttling of Smad1 conferred by its nuclear localization and
      nuclear export signals.
AB  - Smad1 mediates signaling by bone morphogenetic proteins (BMPs). In the resting
      state, Smad1 is found in both the nucleus and cytosol. BMP addition triggers
      Smad1 serine phosphorylation, binding of Smad4, and its accumulation in the
      nucleus. Mutations in the Smad1 N-terminal basic nuclear localization signal
      (NLS)-like motif, conserved among all Smad proteins, eliminated its ligand
      induced nuclear translocation without affecting its other functions, including
      DNA binding and complex formation with Smad4. Addition of leptomycin B, an
      inhibitor of nuclear export, induced rapid nuclear accumulation of Smad1, whereas
      overexpression of CRM1, the receptor for nuclear export, resulted in Smad1 re
      localization to the cytoplasm and inhibition of BMP-induced nuclear accumulation.
      Thus, in addition to the NLS, Smad1 also contains a functional nuclear export
      signal (NES). We identified a leucine-rich NES motif in the C terminus of Smad1;
      its disruption led to constitutive Smad1 nuclear distribution. Reporter gene
      activation assays demonstrated that both the NLS and NES are required for optimal
      transcriptional activation by Smad1. Despite its constitutive nuclear
      accumulation, a Smad1 NES mutant did not display higher basal reporter gene
      activity. We conclude that Smad1 is under constant nucleocytoplasmic shuttling
      conferred by its NLS and NES; nuclear accumulation after ligand-induced
      phosphorylation represents a change in the balance of the activities of these
      opposing signals and is essential for transcriptional activation.

PMID- 11509559
TI  - Methylation-dependent silencing of the reduced folate carrier gene in inherently
      methotrexate-resistant human breast cancer cells.
AB  - The molecular basis of methotrexate resistance was studied in human MDA-MB-231
      breast cancer cells, which are inherently defective in methotrexate uptake and
      lack expression of the reduced folate carrier (RFC). Transfection of MDA-MB-231
      cells with RFC cDNA restored methotrexate uptake and increased methotrexate
      sensitivity by approximately 50-fold. A CpG island in the promoter region of RFC
      was found to be methylated in MDA-MB-231 cells, but was unmethylated in RFC
      expressing, methotrexate-sensitive MCF-7 breast cancer cells. Chromatin
      immunoprecipitation with antibodies against acetylated histones H3 and H4 showed
      that the RFC promoter was enriched for acetylated histones on expressed,
      unmethylated alleles only. Treatment of MDA-MB-231 cells with 5-aza-2'
      deoxycytidine restored RFC expression but also led to increased methotrexate
      efflux and did not reverse methotrexate resistance. This suggests that 5-aza-2'
      deoxycytidine up-regulates both methotrexate uptake and some methotrexate
      resistance mechanism(s). Reverse transcription-polymerase chain reaction analysis
      showed increased expression levels of several ATP-dependent efflux pumps in
      response to 5-aza-2'-deoxycytidine treatment, including P-glycoprotein and
      members of the multidrug resistance-associated protein family. Up-regulation of P
      glycoprotein in response to 5-aza-2'-deoxycytidine was associated with
      demethylation of a CpG island in the MDR1 promoter, whereas the mechanism(s) for
      5-aza-2'-deoxycytidine-induced up-regulation of multidrug resistance-associated
      proteins is probably indirect. Dipyridamole inhibited methotrexate efflux and
      reversed methotrexate resistance in 5-aza-2'-deoxycytidine-treated MDA-MB-231
      cells.

PMID- 11509560
TI  - Molecular interactions of the Gbeta binding domain of the Ste20p/PAK family of
      protein kinases. An isolated but fully functional Gbeta binding domain from
      Ste20p is only partially folded as shown by heteronuclear NMR spectroscopy.
AB  - The transmission of the mating signal of the budding yeast Saccharomyces
      cerevisiae requires Ste20p, a member of the serine/threonine protein kinases of
      the Ste20p/PAK family, to link the Gbeta subunit of the heterotrimeric G protein
      to the mitogen-activated protein kinase cascades. The binding site of Ste20p to
      the Gbeta subunit was mapped to a consensus sequence of SSLphiPLI/VXphiphibeta (X
      for any residue; phi for A, I, L, S or T; beta for basic residues), which was
      shown to be a novel Gbeta binding (GBB) motif present only in the noncatalytic C
      terminal domains of the Ste20p/PAK family of protein kinases (Leeuw, T., Wu, C.,
      Schrag, J. D., Whiteway, M., Thomas, D. Y., and Leberer, E. (1998) Nature 391,
      191-195; Leberer, E., Dignard, D., Thomas, D. Y., and Leeuw, T. (2000) Biol.
      Chem. 381, 427-431). Here, we report the results of an NMR study on two GBB motif
      peptides and the entire C-terminal domain derived from Ste20p. The NMR data show
      that the two peptide fragments are not uniquely structured in aqueous solution,
      but in the presence of 40% trifluoroethanol, the longer 37-residue peptide
      exhibited two well defined, but flexibly linked helical structure elements.
      Heteronuclear NMR data indicate that the fully functional 86-residue C-terminal
      domain of Ste20p is again unfolded in aqueous solution but has helical secondary
      structure preferences similar to those of the two peptide fragments. The NMR
      results on the two GBB peptides and the entire GBB domain all indicate that the
      two important binding residues, Ser(879) and Ser(880), are located at the
      junction between two helical segments. These experimental observations with the
      prototype GBB domain of a novel family of Gbeta-controlled effectors may have
      important implications in understanding the molecular mechanisms of the signal
      transduction from the heterotrimeric G protein to the mitogen-activated protein
      kinase cascade.

PMID- 11509561
TI  - ATP reorients the neck linker of kinesin in two sequential steps.
AB  - Recent models of the kinesin mechanochemical cycle provide some conflicting
      information on how the neck linker contributes to movement. Some spectroscopic
      approaches suggest a nucleotide-induced order-to-disorder transition in the neck
      linker. However, cryoelectron microscopic imaging suggests instead that
      nucleotide alters the orientation of the neck linker when docked on the
      microtubule surface. Furthermore, since these studies utilized transition state
      or non-hydrolyzable nucleotide analogs, it is not clear at what point in the
      ATPase cycle this reorientation of the neck linker occurs. We have addressed this
      issue by developing a strategy to examine the effect of nucleotide on the
      orientation of the neck linker based on the technique of fluorescence resonance
      energy transfer. Transient kinetic studies utilizing this approach support a
      model in which ATP binding leads to two sequential isomerizations, the second of
      which reorients the neck linker in relation to the microtubule surface.

PMID- 11509562
TI  - An essential role for Rac/Cdc42 GTPases in cerebellar granule neuron survival.
AB  - Rho family GTPases are critical molecular switches that regulate the actin
      cytoskeleton and cell function. In the current study, we investigated the
      involvement of Rho GTPases in regulating neuronal survival using primary
      cerebellar granule neurons. Clostridium difficile toxin B, a specific inhibitor
      of Rho, Rac, and Cdc42, induced apoptosis of granule neurons characterized by c
      Jun phosphorylation, caspase-3 activation, and nuclear condensation. Serum and
      depolarization-dependent survival signals could not compensate for the loss of
      GTPase function. Unlike trophic factor withdrawal, toxin B did not affect the
      antiapoptotic kinase Akt or its target glycogen synthase kinase-3beta. The
      proapoptotic effects of toxin B were mimicked by Clostridium sordellii lethal
      toxin, a selective inhibitor of Rac/Cdc42. Although Rac/Cdc42 GTPase inhibition
      led to F-actin disruption, direct cytoskeletal disassembly with Clostridium
      botulinum C2 toxin was insufficient to induce c-Jun phosphorylation or apoptosis.
      Granule neurons expressed high basal JNK and low p38 mitogen-activated protein
      kinase activities that were unaffected by toxin B. However, pyridyl imidazole
      inhibitors of JNK/p38 attenuated c-Jun phosphorylation. Moreover, both pyridyl
      imidazoles and adenoviral dominant-negative c-Jun attenuated apoptosis,
      suggesting that JNK/c-Jun signaling was required for cell death. The results
      indicate that Rac/Cdc42 GTPases, in addition to trophic factors, are critical for
      survival of cerebellar granule neurons.

PMID- 11509563
TI  - Chaperone-like activity of tubulin. binding and reactivation of unfolded
      substrate enzymes.
AB  - The eukaryotic cytoskeletal protein tubulin is a heterodimer of two subunits,
      alpha and beta, and is a building block unit of microtubules. In a previous
      communication we demonstrated that tubulin possesses chaperone-like activities by
      preventing the stress-induced aggregation of various proteins (Guha, S., Manna,
      T. K., Das, K. P., and Bhattacharyya, B. (1998) J. Biol. Chem. 273, 30077-30080).
      As an extension of this observation, we explored whether tubulin, like other
      known chaperones, also protected biological activity of proteins against thermal
      stress or increased the yields of active proteins during refolding from a
      denatured state. We show here that tubulin not only prevents the thermal
      aggregation of alcohol dehydrogenase and malic dehydrogenase but also protects
      them from loss of activity. We also show that tubulin prevents the aggregation of
      substrates during their refolding from a denatured state and forms a stable
      complex with denatured substrate. The activity of malic dehydrogenase, alpha
      glucosidase, and lactate dehydrogenase during their refolding from urea or
      guanidium hydrochloride denatured states increased significantly in presence of
      tubulin compared with that without tubulin. These results suggest that tubulin,
      in addition to its role in mitosis, cell motility, and other cellular events,
      might be implicated in protein folding and protection from stress.

PMID- 11509564
TI  - Distinct binding specificity of the multiple PDZ domains of INADL, a human
      protein with homology to INAD from Drosophila melanogaster.
AB  - PDZ domains are protein-protein interaction modules that typically bind to short
      peptide sequences at the carboxyl terminus of target proteins. Proteins
      containing multiple PDZ domains often bind to different trans-membrane and
      intracellular proteins, playing a central role as organizers of multimeric
      complexes. To characterize the rules underlying the binding specificity of
      different PDZ domains, we have assembled a novel repertoire of random peptides
      that are displayed at high density at the carboxyl terminus of the capsid D
      protein of bacteriophage lambda. We have exploited this combinatorial library to
      determine the peptide binding preference of the seven PDZ domains of human INADL,
      a multi-PDZ protein that is homologous to the INAD protein of Drosophila
      melanogaster. This approach has permitted the determination of the consensus
      ligand for each PDZ domain and the assignment to class I, class II, and to a new
      specificity class, class IV, characterized by the presence of an acidic residue
      at the carboxyl-terminal position. Homology modeling and site-directed
      mutagenesis experiments confirmed the involvement of specific residues at contact
      positions in determining the domain binding preference. However, these
      experiments failed to reveal simple rules that would permit the association of
      the chemical characteristics of any given residue in the peptide binding pocket
      to the preference for specific amino acid sequences in the ligand peptide.
      Rather, they suggested that to infer the binding preference of any PDZ domain, it
      is necessary to simultaneously take into account all contact positions by using
      computational procedures. For this purpose we extended the SPOT algorithm,
      originally developed for SH3 domains, to evaluate the probability that any
      peptide would bind to any given PDZ domain.

PMID- 11509565
TI  - The role of AP-1 in the transcriptional regulation of the rat apical sodium
      dependent bile acid transporter.
AB  - Ileal reclamation of bile salts, a critical determinant of their enterohepatic
      circulation, is mediated primarily by the apical sodium-dependent bile acid
      transporter (ASBT=SLC10A2). We have defined mechanisms involved in the
      transcriptional regulation of ASBT. The ASBT gene extends over 17 kilobases and
      contains five introns. Primer extension analysis localized two transcription
      initiation sites 323 and 255 base pairs upstream of the initiator methionine.
      Strong promoter activity is imparted by both a 2.7- and 0.2-kilobase 5'-flanking
      region of ASBT. The promoter activity is cell line specific (Caco-2, not Hep-G2,
      HeLa-S3, or Madin-Darby canine kidney cells). Four distinct specific binding
      proteins were identified by gel shift and cross-linking studies using Caco-2 or
      rat ileal nuclear extracts. Two AP-1 consensus sites were identified in the
      proximal promoter. DNA binding and promoter activity could be abrogated by
      mutation of the proximal AP-1 site. Supershift analysis revealed binding of c-Jun
      and c-Fos to this AP-1 element. Co-expression of c-Jun enhanced promoter activity
      in Caco-2 cells and activated the promoter in Madin-Darby canine kidney cells.
      Region and developmental stage-specific expression of ASBT in the rat intestine
      correlated with the presence of one of these DNA-protein complexes and both c-Fos
      and c-Jun proteins. A specific AP-1 element regulates transcription of the rat
      ASBT gene.

PMID- 11509566
TI  - Cloning and characterization of an alternatively spliced form of SR protein
      kinase 1 that interacts specifically with scaffold attachment factor-B.
AB  - Serine/arginine protein kinases have been conserved throughout evolution and are
      thought to play important roles in the regulation of mRNA processing, nuclear
      import, germline development, polyamine transport, and ion homeostasis. Human
      SRPK1, which was first identified as a kinase specific for the SR family of
      splicing factors, is located on chromosome 6p21.2-p21.3. We report here the
      cloning and characterization of SRPK1a, which is encoded by an alternatively
      processed transcript derived from the SRPK1 gene. SRPK1a contains an insertion of
      171 amino acids at its NH(2)-terminal domain and is similar to SRPK1 in substrate
      specificity and subcellular localization. Moreover, both isoforms can induce
      alternative splicing of human tau exon 10 in transfected cells. Using the yeast
      two-hybrid assay, we found that the extended NH(2)-terminal domain of SRPK1a
      interacts with Scaffold Attachment Factor-B, a nuclear scaffold-associated
      protein. Confirmation of this interaction was provided by in vitro binding
      assays, as well as by co-immunoprecipitation from 293T cells doubly transfected
      with SRPK1a and SAF-B. Our studies suggest that different SRPK family members are
      uniquely regulated and targeted and thus the multiple SRPK kinases present in
      higher eukaryotes may perform specialized and differentiable functions.

PMID- 11509567
TI  - Identification and characterization of a novel androgen receptor coregulator
      ARA267-alpha in prostate cancer cells.
AB  - The androgen receptor (AR) is a member of the steroid receptor superfamily that
      binds to the androgen response element to regulate target gene transcription. AR
      may need to interact with some selected coregulators for maximal or proper
      androgen function. Here we report the isolation of a new AR coregulator with a
      calculated molecular mass of 267 kDa named the androgen receptor-associated
      protein 267-alpha (ARA267-alpha). ARA267-alpha contains 2427 amino acids,
      including one Su(var)3-9, Enhancer-of-zeste, and Trithorax (SET) domain, two
      LXXLL motifs, three nuclear translocation signal (NLS) sequences, and four plant
      homeodomain (PHD) finger domains. Northern blot analyses reveal that ARA267-alpha
      is expressed predominantly in the lymph node as 13- and 10-kilobase transcripts.
      HepG2 is the only cell line tested that does not express ARA267-alpha. Yeast two
      hybrid and glutathione S-transferase pull-down assays show that both the N and C
      terminus of ARA267-alpha interact with the AR DNA- and ligand-binding domains.
      Unlike other coregulators, such as CBP, which enhance the interaction between the
      N and C terminus of AR, we found that ARA267-alpha had little influence on the
      interaction between the N and C terminus of AR. Luciferase and chloramphenicol
      acetyltransferase assays show that ARA267-alpha can enhance AR transactivation in
      a dihydrotestosterone-dependent manner in PC-3 and H1299 cells. ARA267-alpha can
      also enhance AR transactivation with other coregulators, such as ARA24 or PCAF, a
      histone acetylase, in an additive manner. Together, our data demonstrate that
      ARA267-alpha is a new AR coregulator containing the SET domain with an
      exceptionally large molecular mass that can enhance AR transactivation in
      prostate cancer cells.

PMID- 11509568
TI  - Role of the FYVE finger and the RUN domain for the subcellular localization of
      Rabip4.
AB  - Rabip4 is a Rab4 effector, which possesses a RUN domain, two coiled-coil domains,
      and a FYVE finger. It is associated with the early endosomes and leads, in
      concert with Rab4, to the enlargement of endosomes, resulting in the fusion of
      sorting and recycling endosomes. Our goal was to characterize the role of these
      various domains in Rabip4 subcellular localization and their function in Chinese
      hamster ovary cells. Although the FYVE finger domain specifically bound
      phosphatidylinositol 3-phosphate and was necessary for the function of Rabip4, it
      was not sufficient for the protein association with membranes. Indeed a protein
      containing the FYVE finger and the Rab4-binding site was cytosolic, whereas the
      total protein was mostly associated to the membrane fraction, whether or not
      cells were pretreated with wortmannin. By contrast, a construct corresponding to
      the N-terminal end, Rabip4-(1-212), and containing the RUN domain was membrane
      associated. The complete protein partitioned between the Triton X-100-insoluble
      and -soluble fractions and a wortmannin treatment increased the amount of the
      protein in the Triton X-100 fraction. Rabip4-(1-212) was totally Triton X-100
      insoluble, and confocal microscopic examination showed that it labeled not only
      the endosomes, positive for Rabip4, but also a filamentous network with a
      honeycomb appearance. The Triton X-100-insoluble fraction that contains Rabip4
      did not correspond to the caveolin or glycosylphosphatidylinositol-enriched lipid
      rafts. Rabip4 did not appear directly linked to actin but seemed associated to
      the actin network. We propose that the subcellular localization of the protein is
      primarily driven by the RUN domain to endosomal microdomains characterized by
      Triton X-100 insolubility and that the FYVE domain and the Rab4-binding domain
      then allow for the recruitment of the protein to lipophilic microdomains enriched
      in phosphatidylinositol 3-phosphate.

PMID- 11509569
TI  - Enhancement of fibroblast growth factor (FGF) activity by an FGF-binding protein.
AB  - Fibroblast growth factor-binding protein (FGF-BP) 1 is a secreted protein that
      can bind fibroblast growth factors (FGFs) 1 and 2. These FGFs are typically
      stored on heparan sulfate proteoglycans in the extracellular matrix in an
      inactive form, and it has been proposed that FGF-BP1 functions as a chaperone
      molecule that can mobilize locally stored FGF and present the growth factor to
      its tyrosine kinase receptor. FGF-BP1 is up-regulated in squamous cell, colon,
      and breast cancers and can act as an angiogenic switch during malignant
      progression of epithelial cells. For the present studies, we focused on FGF-1 and
      -2 and investigated interactions with recombinant human FGF-BP1 protein as well
      as effects on signal transduction, cell proliferation, and angiogenesis. We show
      that recombinant FGF-BP1 specifically binds FGF-2 and that this binding is
      inhibited by FGF-1, heparan sulfate, and heparinoids. Furthermore, FGF-BP1
      enhances FGF-1- and FGF-2-dependent proliferation of NIH-3T3 fibroblasts and FGF
      2-induced extracellular signal-regulated kinase 2 phosphorylation. Finally, in
      the chicken chorioallantoic membrane angiogenesis assay, FGF-BP1 synergizes with
      exogenously added FGF-2. We conclude that FGF-BP1 binds directly to FGF-1 and FGF
      2 and positively modulates the biological activities of these growth factors.

PMID- 11509570
TI  - Interaction between Ran and Mog1 is required for efficient nuclear protein
      import.
AB  - Mog1 is a nuclear protein that interacts with Ran, the Ras family GTPase that
      confers directionality to nuclear import and export pathways. Deletion of MOG1 in
      Saccharomyces cerevisiae (Deltamog1) causes temperature-sensitive growth and
      defects in nuclear protein import. Mog1 has previously been shown to stimulate
      GTP release from Ran and we demonstrate here that addition of Mog1 to either Ran
      GTP or Ran-GDP results in nucleotide release and formation of a stable complex
      between Mog1 and nucleotide-free Ran. Moreover, MOG1 shows synthetic lethality
      with PRP20, the Ran guanine nucleotide exchange factor (RanGEF) that also binds
      nucleotide-free Ran. To probe the functional role of the Mog1-Ran interaction, we
      engineered mutants of yeast Mog1 and Ran that specifically disrupt their
      interaction both in vitro and in vivo. These mutants indicate that the
      interaction interface involves conserved Mog1p residues Asp(62) and Glu(65), and
      residue Lys(136) in yeast Ran. Mutations at these residues decrease the ability
      of Mog1 to bind and release nucleotide from Ran. Furthermore, the E65K-Mog1 and
      K136E-Ran mutations in yeast cause temperature sensitivity and mislocalization of
      a nuclear import reporter protein, similar to the phenotype observed for the
      Deltamog1 strain. Our results indicate that a primary function of Mog1 requires
      binding to Ran and that the Mog1-Ran interaction is necessary for efficient
      nuclear protein import in vivo.

PMID- 11509571
TI  - Direct interaction of the spinal muscular atrophy disease protein SMN with the
      small nucleolar RNA-associated protein fibrillarin.
AB  - Disruption of the survival motor neuron (SMN) gene leads to selective loss of
      spinal motor neurons, resulting in the fatal human neurodegenerative disorder
      spinal muscular atrophy (SMA). SMN has been shown to function in spliceosomal
      small nuclear ribonucleoprotein (snRNP) biogenesis and pre-mRNA splicing. We have
      demonstrated that SMN also interacts with fibrillarin, a highly conserved
      nucleolar protein that is associated with all Box C/D small nucleolar RNAs and
      functions in processing and modification of rRNA. Fibrillarin and SMN co
      immunoprecipitate from HeLa cell extracts indicating that the proteins exist as a
      complex in vivo. Furthermore, in vitro binding studies indicate that the
      interaction between SMN and fibrillarin is direct and salt-stable. We show that
      the glycine/arginine-rich domain of fibrillarin is necessary and sufficient for
      SMN binding and that the region of SMN encoded by exon 3, including the Tudor
      domain, mediates the binding of fibrillarin. Tudor domain missense mutations,
      including one found in an SMA patient, impair the interaction between SMN and
      fibrillarin (as well as the common snRNP protein SmB). Our results suggest a
      function for SMN in small nucleolar RNP biogenesis (akin to its known role as an
      snRNP assembly factor) and reveal a potential link between small nucleolar RNP
      biogenesis and SMA.

PMID- 11509572
TI  - The DNA-binding domain of yeast heat shock transcription factor independently
      regulates both the N- and C-terminal activation domains.
AB  - The expression of heat shock proteins in response to cellular stresses is
      dependent on the activity of the heat shock transcription factor (HSF). In yeast,
      HSF is constitutively bound to DNA; however, the mitigation of negative
      regulation in response to stress dramatically increases transcriptional activity.
      Through alanine-scanning mutagenesis of the surface residues of the DNA-binding
      domain, we have identified a large number of mutants with increased
      transcriptional activity. Six of the strongest mutations were selected for
      detailed study. Our studies suggest that the DNA-binding domain is involved in
      the negative regulation of both the N-terminal and C-terminal activation domains
      of HSF. These mutations do not significantly affect DNA binding. Circular
      dichroism analysis suggests that a subset of the mutants may have altered
      secondary structure, whereas a different subset has decreased thermal stability.
      Our findings suggest that the regulation of HSF transcriptional activity (under
      both constitutive and stressed conditions) may be partially dependent on the
      local topology of the DNA-binding domain. In addition, the DNA-binding domain may
      mediate key interactions with ancillary factors and/or other intramolecular
      regulatory regions in order to modulate the complex regulation of HSF's
      transcriptional activity.

PMID- 11509573
TI  - Disrupted bile acid homeostasis reveals an unexpected interaction among nuclear
      hormone receptors, transporters, and cytochrome P450.
AB  - Sister of P-glycoprotein (SPGP) is the major hepatic bile salt export pump
      (BSEP). BSEP/SPGP expression varies dramatically among human livers. The potency
      and hierarchy of bile acids as ligands for the farnesyl/bile acid receptor
      (FXR/BAR) paralleled their ability to induce BSEP in human hepatocyte cultures.
      FXR:RXR heterodimers bound to IR1 elements and enhanced bile acid transcriptional
      activation of the mouse and human BSEP/SPGP promoters. In FXR/BAR nullizygous
      mice, which have dramatically reduced BSEP/SPGP levels, hepatic CYP3A11 and
      CYP2B10 were strongly but unexpectedly induced. Notably, the rank order of bile
      acids as CYP3A4 inducers and activators of pregnane X receptor/steroid and
      xenobiotic receptor (PXR/SXR) closely paralleled each other but was markedly
      different from their hierarchy and potency as inducers of BSEP in human
      hepatocytes. Moreover, the hepatoprotective bile acid ursodeoxycholic acid, which
      reverses hydrophobic bile acid hepatotoxicity, activates PXR and efficaciously
      induces CYP3A4 (a bile-metabolizing enzyme) in primary human hepatocytes thus
      providing one mechanism for its hepatoprotection. Because serum and urinary bile
      acids increased in FXR/BAR -/- mice, we evaluated hepatic transporters for
      compensatory changes that might circumvent the profound decrease in BSEP/SPGP. We
      found weak MRP3 up-regulation. In contrast, MRP4 was substantially increased in
      the FXR/BAR nullizygous mice and was further elevated by cholic acid. Thus,
      enhanced hepatocellular concentrations of bile acids, due to the down-regulation
      of BSEP/SPGP-mediated efflux in FXR nullizygous mice, result in an alternate but
      apparent compensatory up-regulation of CYP3A, CYP2B, and some ABC transporters
      that is consistent with activation of PXR/SXR by bile acids.

PMID- 11509575
TI  - Positive and negative regulation of NF-kappaB by COX-2: roles of different
      prostaglandins.
AB  - The prostaglandin H synthases (PGHS) catalyze the conversion of arachidonic acid
      to prostaglandin H(2), the committed step in prostanoid synthesis. Two forms of
      PGHS exist, PGHS-1 (COX-1) and PGHS-2 (COX-2). The gene encoding the latter form
      is known to be inducible by a number of stimuli including several inflammatory
      mediators. Recent evidence indicates that the inducible cyclooxygenase may have
      both pro- and anti-inflammatory properties through the generation of different
      prostaglandins. Previous reports indicate that the transcription factor NF-kappaB
      can function upstream of COX-2 to control transcription of this gene and that the
      cyclopentenone prostaglandins can inhibit NF-kappaB activation via the inhibition
      of the IkappaB kinase. Thus, it is suggested that cyclopentenones feed back to
      inhibit continued nuclear accumulation of NF-kappaB. In this report we
      demonstrate COX-2 expression inhibits nuclear translocation of NF-kappaB, and we
      confirm that the cyclopentenone prostaglandins inhibit NF-kappaB. In addition, we
      show that prostaglandin E(2) and its analogs promote the inherent transcriptional
      activity of the p65/RelA subunit of NF-kappaB in a manner independent of induced
      nuclear accumulation. Consistent with this evidence, prostaglandin E(2) strongly
      synergizes with the inflammatory cytokine tumor necrosis factor-alpha to promote
      NF-kappaB-dependent transcription and gene expression. The data provide a
      molecular rationale to explain both the pro- and anti-inflammatory nature of COX
      2.

PMID- 11509574
TI  - Structural and functional interactions of transcription factor (TF) IIA with
      TFIIE and TFIIF in transcription initiation by RNA polymerase II.
AB  - A topological model for transcription initiation by RNA polymerase II (RNAPII)
      has recently been proposed. This model stipulates that wrapping of the promoter
      DNA around RNAPII and the general initiation factors TBP, TFIIB, TFIIE, TFIIF and
      TFIIH induces a torsional strain in the DNA double helix that facilitates strand
      separation and open complex formation. In this report, we show that TFIIA, a
      factor previously shown to both stimulate basal transcription and have co
      activator functions, is located near the cross-point of the DNA loop where it can
      interact with TBP, TFIIE56, TFIIE34, and the RNAPII-associated protein (RAP) 74.
      In addition, we demonstrate that TFIIA can stimulate basal transcription by
      stimulating the functions of both TFIIE34 and RAP74 during the initiation step of
      the transcription reaction. These results provide novel insights into mechanisms
      of TFIIA function.

PMID- 11509576
TI  - The LIS1-related protein NUDF of Aspergillus nidulans and its interaction partner
      NUDE bind directly to specific subunits of dynein and dynactin and to alpha- and
      gamma-tubulin.
AB  - The NUDF protein of Aspergillus nidulans, which is required for nuclear migration
      through the fungal mycelium, closely resembles the LIS1 protein required for
      migration of neurons to the cerebral cortex in humans. Genetic experiments
      suggested that NUDF influences nuclear migration by affecting cytoplasmic dynein.
      NUDF interacts with another protein, NUDE, which also affects nuclear migration
      in A. nidulans. Interactions among LIS1, NUDE, dynein, and gamma-tubulin have
      been demonstrated in animal cells. In this paper we examine the interactions of
      the A. nidulans NUDF and NUDE proteins with components of dynein, dynactin, and
      with alpha- and gamma-tubulin. We show that NUDF binds directly to alpha- and
      gamma-tubulin and to the first P-loop of the cytoplasmic dynein heavy chain,
      whereas NUDE binds directly to alpha- and gamma-tubulin, to NUDK (actin-related
      protein 1), and to the NUDG dynein LC8 light chain. The data suggest a direct
      role for NUDF in regulation of the dynein heavy chain and an effect on other
      dynein/dynactin subunits via NUDE. The interactions between NUDE, NUDF, and gamma
      tubulin suggest that this protein may also be involved in the regulation of
      dynein function. Additive interactions between NUDE and dynein and dynactin
      subunits suggest that NUDE acts as a scaffolding factor between components.

PMID- 11509577
TI  - Diversity in mechanisms of substrate oxidation by cytochrome P450 2D6. Lack of an
      allosteric role of NADPH-cytochrome P450 reductase in catalytic regioselectivity.
AB  - Cytochrome P450 (P450) 2D6 was first identified as the polymorphic human
      debrisoquine hydroxylase and subsequently shown to catalyze the oxidation of a
      variety of drugs containing a basic nitrogen. Differences in the regioselectivity
      of oxidation products formed in systems containing NADPH-P450 reductase/NADPH and
      the model oxidant cumene hydroperoxide have been proposed by others to be due to
      an allosteric influence of the reductase on P450 2D6 (Modi, S., Gilham, D. E.,
      Sutcliffe, M. J., Lian, L.-Y., Primrose, W. U., Wolf, C. R., and Roberts, G. C.
      K. (1997) Biochemistry 36, 4461-4470). We examined the differences in the
      formation of oxidation products of N-methyl-4-phenyl-1,2,5,6-tetrahydropyridine,
      metoprolol, and bufuralol between reductase-, cumene hydroperoxide-, and
      iodosylbenzene-supported systems. Catalytic regioselectivity was not influenced
      by the presence of the reductase in any of the systems supported by model
      oxidants, ruling out allosteric influences. The presence of the reductase had
      little effect on the affinity of P450 2D6 for any of these three substrates. The
      addition of the reaction remnants of the model oxidants (cumyl alcohol and
      iodobenzene) to the reductase-supported system did not affect reaction patterns,
      arguing against steric influences of these products on catalytic
      regioselectivity. Label from H(2)18O was quantitatively incorporated into 1'
      hydroxybufuralol in the iodosylbenzene- but not in the reductase- or cumene
      hydroperoxide-supported reactions. We conclude that the P450 systems utilizing
      NADPH-P450 reductase, cumene hydroperoxide, and iodosylbenzene use similar but
      distinct chemical mechanisms. These differences are the basis for the variable
      product distributions, not an allosteric influence of the reductase.

PMID- 11509578
TI  - mDia-interacting protein acts downstream of Rho-mDia and modifies Src activation
      and stress fiber formation.
AB  - The formin homology protein mDia is a Rho GTPase effector protein that
      participates in stress fiber formation, cytokinesis, and transcriptional
      activation of the serum response factor. Although the function of another
      effector of Rho, Rho-associated kinase, is well established, relatively little is
      known about the functional mechanism and the downstream targets of mDia. Our
      recent report of a Rho-mDia-Src-tyrosine kinase pathway suggested an important
      role for mDia in cell adhesion turnover. We identified a new mDia-interacting
      protein which is expressed ubiquitously. The new protein mainly binds to the
      proline-rich region of mDia through its Src homology 3 domain and also binds to
      Grb2 through its proline-rich domain. The protein is localized at the cell
      periphery and membrane ruffles and co-localizes with mDia. Co-expression of vSrc
      and the mDia-interacting protein induces significant morphological changes at
      focal contacts and activation of vSrc. Furthermore, we found that the mDia
      interacting protein plays an important role in stress fiber formation induced by
      active mDia1. Our results suggest that this new protein regulates actin
      polymerization and cell adhesion turnover in the downstream portion of the Rho
      mDia pathway by interacting with Grb2 and Src.

PMID- 11509579
TI  - Cutting edge: culture with high doses of viral peptide induces previously
      unprimed CD8(+) T cells to produce cytokine.
AB  - Culturing naive T cells with 50 microM selected HIV-1 envelope peptides for 6
      days in the presence of IL-2 drives the emergence of a substantial CD8(+)
      population that secretes IFN-gamma following short-term stimulation with 1 microM
      peptide. This response is H-2K(b) restricted, epitope specific, and requires the
      continuing presence of peptide. The same effect was found for known H-2D(b)
      restricted peptides from two influenza virus proteins. The great majority of
      these influenza-specific CD8(+)IFN-gamma(+) T cells neither stained with the
      cognate tetramer nor expressed the TCR Vbeta bias that is characteristic of the
      CD8(+) set expanded in vivo during an infection. Thus, multipoint binding of low
      affinity TCRs on naive CD8(+) T cells can drive peptide-specific cytokine
      production. However, at least for two influenza-derived epitopes, the avidity of
      the TCR-MHC peptide interaction appears to be insufficient to stabilize a
      tetrameric complex of MHC class I glycoprotein plus peptide on the lymphocyte
      surface.

PMID- 11509580
TI  - Cutting edge: dichotomy of homing receptor dependence by mucosal effector B
      cells: alpha(E) versus L-selectin.
AB  - The common mucosal immune system may be compartmentalized because lymphocyte
      homing to the upper respiratory tract appears to be mediated by L-selectin
      interactions rather than alpha(4)beta(7) interactions, as is the case for gut
      associated lymphoreticular tissue. To assess the role of L-selectin in effector B
      cell immunity, L-selectin-deficient mice were intranasally immunized with cholera
      toxin (CT), and mucosal immune responses were compared with C57BL/6 mice. The
      absence of L-selectin correlated with a reduction in CT-specific secretory-IgA
      responses in nasal passages and reproductive tract, but not intestinal lamina
      propria. Cell sorting experiments showed that an L-selectin-dependent subset was
      responsible for CT-specific responses in nasal passages and reproductive tract,
      whereas an alpha(E)beta(7)(+) B cell subset was responsible for L-selectin
      independent intestinal immunity. This study provides evidence for
      compartmentalization of the common mucosal immune system into "intestinal" vs
      "nonintestinal" effector sites.

PMID- 11509581
TI  - Cutting edge: myeloid complement C3 enhances the humoral response to peripheral
      viral infection.
AB  - HSV-1 is the causative agent of cutaneous lesions, commonly referred to as cold
      sores. Primary exposure to the virus ordinarily occurs through the periphery, in
      particular through abraded skin or mucosal membranes. Under certain circumstances
      (e.g., in neonatals or AIDS patients), the infection becomes disseminated, often
      with severe consequences. Spread of HSV-1 is limited by virus-specific Ab. The
      development of an efficient humoral response to the virus is dependent on innate
      immunity component complement C3. The liver is the major source of C3, but there
      are also extrahepatic origins of C3 such as lymphoid macrophages. In the present
      study, the significance of C3 synthesis by bone marrow-derived cells was assessed
      by the transfer of wild-type bone marrow into irradiated C3-deficient mice. Using
      these chimeric mice, extrahepatic C3 was determined sufficient to initiate
      specific Ab and memory responses to a peripheral HSV-1 infection.

PMID- 11509582
TI  - Cutting edge: amelioration of kidney disease in a transgenic mouse model of lupus
      nephritis by administration of the caspase inhibitor carbobenzoxy-valyl-alanyl
      aspartyl-(beta-o-methyl)-fluoromethylketone.
AB  - Systemic lupus erythematosus (SLE) is a common, potentially fatal, non-organ
      specific autoimmune disorder. Immune complex-mediated kidney disease is the major
      cause of mortality. Apoptotic cells in the epidermis are a possible source of
      self Ags, and apoptosis of endothelial cells and lymphocytes is thought to
      contribute to end-organ damage. We have previously shown that female transgenic
      mice expressing IFN-gamma in the epidermis develop inflammatory skin disease and
      features of SLE that have striking parallels with the human condition. We have
      now tested the effects of a pan-caspase inhibitor, carbobenzoxy-valyl-alanyl
      aspartyl-(beta-o-methyl)-fluoromethylketone, on disease progression. Daily s.c.
      administration of carbobenzoxy-valyl-alanyl-aspartyl-(beta-o-methyl)
      fluoromethylketone to female transgenic mice over a 3-wk period resulted in
      significant amelioration of both glomerular and interstitial renal damage,
      independent of the effects on autoantibody levels or skin inflammation. We
      propose that apoptosis inhibitors could be beneficial in the treatment of human
      SLE.

PMID- 11509583
TI  - Technical note: linkage disequilibrium and disease-associated CTLA4 gene
      polymorphisms.
AB  - CTLA4 and CD28 are important regulators of T lymphocyte activation. Gene region
      2q33 carrying genes for both CTLA4 and CD28 has been shown to be linked to many
      autoimmune diseases. Disease associations with particular CTLA4 gene
      polymorphisms have been reported. Recently, first lines of evidence emerged for
      functional effects of CTLA4 gene polymorphisms. Two independent studies reported
      a reduced inhibitory function of CTLA4 in individuals with certain CTLA4
      genotypes: those with a high number of microsatellite repeats in one study and
      those with allele +49*G in exon 1 in the other one. We analyzed the strength of
      linkage disequilibrium between the three known CTLA4 polymorphisms among 577
      independent chromosomes. Our results show that the polymorphisms previously
      suggested to be the functional risk factors nearly always occur together in a
      very frequent haplotype. Due to this strong linkage disequilibrium, we conclude
      that the previous reports studying merely a single polymorphism could not
      distinguish which variation actually caused the functional difference. Hence,
      either mutagenesis approaches or studies with data on all linked polymorphisms
      are still needed to determine the genuine functional risk polymorphism in this
      gene region.

PMID- 11509584
TI  - Role of CD47 in the induction of human naive T cell anergy.
AB  - We recently reported that CD47 ligation inhibited IL-2 release by umbilical cord
      blood mononuclear cells activated in the presence of IL-12, but not IL-4,
      preventing the induction of IL-12Rbeta(2) expression and the acquisition of Th1,
      but not the Th2 phenotype. Here we show that in the absence of exogenous cytokine
      at priming, CD47 ligation of umbilical cord blood mononuclear cells promotes the
      development of hyporesponsive T cells. Naive cells were treated with CD47 mAb for
      3 days, expanded in IL-2 for 9-12 days, and restimulated by CD3 and CD28
      coengagement. Effector T cells generated under these conditions were considered
      to be anergic because they produced a reduced amount of IL-2 at the single-cell
      level and displayed an impaired capacity 1) to proliferate, 2) to secrete Th1/Th2
      cytokines, and 3) to respond to IL-2, IL-4, or IL-12. Moreover, CD47 mAb strongly
      suppressed IL-2 production and IL-2Ralpha expression in primary cultures and IL-2
      response of activated naive T cells. Induction of anergy by CD47 mAb was IL-10
      independent, whereas inclusion of IL-2 and IL-4, but not IL-7, at priming fully
      restored T cell activation. Furthermore, CD28 costimulation prevented induction
      of anergy. Thus, CD47 may represent a potential target to induce anergy and
      prevent undesired Th0/Th1 responses such as graft vs host diseases, allograft
      rejection, or autoimmune diseases.

PMID- 11509585
TI  - A CD19-dependent signaling pathway regulates autoimmunity in Lyn-deficient mice.
AB  - CD19 and the Src family protein tyrosine kinases (PTKs) are important regulators
      of intrinsic signaling thresholds in B cells. Regulation is achieved by cross
      talk between Src family PTKs and CD19; Lyn is essential for CD19 phosphorylation,
      while CD19 establishes an Src family PTK activation loop that amplifies kinase
      activity. However, CD19-deficient (CD19(-/-)) B cells are hyporesponsive to
      transmembrane signals, while Lyn-deficient (Lyn(-/-)) B cells exhibit a hyper
      responsive phenotype resulting in autoimmunity. To identify the outcome of
      interactions between CD19 and Src family PTKs in vivo, B cell function was
      examined in mice deficient for CD19 and Lyn (CD19/Lyn(-/-)). Remarkably, CD19
      deficiency suppressed the hyper-responsive phenotype of Lyn(-/-) B cells and
      autoimmunity characterized by serum autoantibodies and immune complex-mediated
      glomerulonephritis in Lyn(-/-) mice. Consistent with Lyn and CD19 each regulating
      conventional B cell development, B1 cell development was markedly reduced by Lyn
      deficiency, with further reductions in the absence of CD19 expression. Tyrosine
      phosphorylation of Fyn and other cellular proteins induced following B cell Ag
      receptor ligation was dramatically reduced in CD19/Lyn(-/-) B cells relative to
      Lyn(-/-) B cells, while Syk phosphorylation was normal. In addition, the enhanced
      intracellular Ca(2+) responses following B cell Ag receptor ligation that typify
      Lyn deficiency were delayed by the loss of CD19 expression. BCR-induced
      proliferation and humoral immune responses were also markedly inhibited by
      CD19/Lyn deficiency. These findings demonstrate that while the CD19/Lyn
      amplification loop is a major regulator of signal transduction thresholds in B
      lymphocytes, CD19 regulation of other Src family PTKs also influences B cell
      function and the development of autoimmunity.

PMID- 11509586
TI  - The TNF superfamily members LIGHT and CD154 (CD40 ligand) costimulate induction
      of dendritic cell maturation and elicit specific CTL activity.
AB  - LIGHT is a recently identified member of the TNF superfamily that is up-regulated
      upon activation of T cells. Herpesvirus entry mediator, one of its receptors, is
      constitutively expressed on immature dendritic cells (DCs). In this report, we
      demonstrate that LIGHT induces partial DC maturation as demonstrated by Ag
      presentation and up-regulation of adhesion and costimulatory molecules. LIGHT
      stimulated DCs show reduced macropinocytosis and enhanced allogeneic stimulatory
      capacity but fail to produce significant amounts of IL-12, IL-6, IL-1beta, or TNF
      alpha compared with unstimulated DCs. However, LIGHT cooperates with CD154 (CD40
      ligand) in DC maturation, with particular potentiation of allogeneic T cell
      proliferation and cytokine secretion of IL-12, IL-6, and TNF-alpha. Moreover,
      LIGHT costimulation allows DCs to prime in vitro-enhanced specific CTL responses.
      Our results suggest that LIGHT plays an important role in DC-mediated immune
      responses by regulating CD154 signals and represents a potential tool for DC
      based cancer immunotherapy.

PMID- 11509587
TI  - IFN-gamma induces the apoptosis of WEHI 279 and normal pre-B cell lines by
      expressing direct inhibitor of apoptosis protein binding protein with low pI.
AB  - Interferon-gamma plays a crucial role in induction of Th1 response but is
      predominantly a negative regulator of B cell differentiation and Th2 response, so
      it is a key molecule in determining cellular or humoral immunity. In this study,
      we demonstrate that IFN-gamma induces apoptosis in WEHI 279 mouse B cells and IL
      7-dependent mouse pre-B cells by disrupting mitochondrial membrane potential and
      cytochrome c release via down-regulation of Bcl-2 and Bcl-x(L). Furthermore, this
      apoptotic signal is promoted by the de novo synthesis of endogenous direct
      inhibitor of apoptosis protein binding protein with low pI (DIABLO) by IFN-gamma
      and its release from mitochondria into the cytosol. Inhibition of DIABLO
      expression by antisense oligonucleotide is sufficient to decrease caspase
      activities and DNA fragmentation, but not cytochrome c release from mitochondria,
      suggesting that DIABLO plays a critical role in promoting apoptotic signals
      downstream of mitochondrial events. Thus, these findings demonstrate a signaling
      pathway during B cell apoptosis induced by IFN-gamma and possible mechanisms by
      which B cell differentiation is negatively regulated by Th1-type cytokines.

PMID- 11509588
TI  - Double-stranded RNA regulates IL-4 expression.
AB  - dsRNA, as genomic fragment, replicative intermediate, or stem and loop structure
      in cells infected by viruses, can act to signal the immune system of the presence
      of viral infections. Although most viral infections are associated with strong
      Th1 immune responses, Th2-type responses have also been observed. In this study,
      we characterize the effects of dsRNA on the induction of Th2 responses in human
      lymphocytes. We report that in addition to the well-known Th1-inducing
      capabilities of dsRNA, treatment of human lymphocytes with low concentrations of
      dsRNA (0.1-1 microg/ml) leads to the expression of the prototypic Th2 cytokine IL
      4. This induction was accompanied with the concentration-dependent activation of
      NF-kappaB and NF-AT2 but not NF-AT1. In addition, dsRNA can directly activate an
      IL-4 promoter-driven chloramphenicol acetyltransferase reporter gene in
      transiently transfected Jurkat cells. These results are the first demonstration
      of a non-TCR-associated activator of NF-AT in human cells and suggest that dsRNA
      directly influences IL-4 gene expression through its effect on NF-AT activation.
      Our data provide support for the idea that dsRNA at low concentrations in vivo
      may induce a Th2-dominant response that is not optimal for protective immunity to
      the virus.

PMID- 11509589
TI  - Suppression of granulocyte-macrophage colony-stimulating factor expression by
      glucocorticoids involves inhibition of enhancer function by the glucocorticoid
      receptor binding to composite NF-AT/activator protein-1 elements.
AB  - Increased expression of a number of cytokines including GM-CSF is associated with
      chronic inflammatory conditions such as bronchial asthma. Glucocorticoid therapy
      results in suppression of cytokine levels by a mechanism(s) not yet fully
      understood. We have examined regulation of GM-CSF expression by the synthetic
      glucocorticoid dexamethasone in human T cells. Transient transfection assays with
      reporter constructs revealed that dexamethasone inhibited the function of the GM
      CSF enhancer, but had no effect on regulation of GM-CSF expression occurring
      through the proximal promoter. Activation of the GM-CSF enhancer involves
      cooperative interaction between the transcription factors NF-AT and AP-1. We
      demonstrate here that glucocorticoid-mediated inhibition of enhancer function
      involves glucocorticoid receptor (GR) binding to the NF-AT/AP-1 sites. These
      elements, which do not constitute recognizable glucocorticoid response elements,
      support binding of the GR, primarily as a dimer. This binding correlates with the
      ability of dexamethasone to inhibit enhancer activity of the NF-AT/AP-1 elements,
      suggesting a competition between NF-AT/AP-1 proteins and GR.

PMID- 11509590
TI  - Expression of alpha(4)beta(7) integrin defines a distinct pathway of lymphoid
      progenitors committed to T cells, fetal intestinal lymphotoxin producer, NK, and
      dendritic cells.
AB  - During embryogenesis, the Peyer's patch anlagen are induced by a cell population
      that produces lymphotoxin (LT) alpha(1)beta(2) following stimulation of IL
      7Ralpha. In this study, we show that the LT-producing cell is localized within
      the IL-7Ralpha(+) and integrin alpha(4)beta(7) (alpha(4)beta(7))(+) population in
      the embryonic intestine. Lineage commitment to the LT producer phenotype in the
      fetal liver coincides with expression of alpha(4)beta(7). Before expression of
      alpha(4)beta(7), the potential of IL-7Ralpha(+) population to generate B cells is
      lost. However, the progenitors for T cells and LT producer cells reside in the IL
      7Ralpha(+)alpha(4)beta(7)(+) cells, but during subsequent differentiation, the
      potential to give rise to T cells is lost. This IL-7Ralpha(+)alpha(4)beta(7)(+)
      population migrates to the intestine, where it induces the Peyer's patch anlagen.
      When stimulated with IL-15 or IL-3 and TNF, the intestinal IL
      7Ralpha(+)alpha(4)beta(7)(+) population can differentiate into fully competent
      NK1.1(+) NK cells or CD11c(+) APCs. Expression of alpha(4)beta(7) is lost during
      differentiation of both lineages; IL-7Ralpha expression is lost during NK1.1(+)
      cells differentiation. A newly discovered lineage(-)IL-7Ralpha(+)c
      Kit(+)alpha(4)beta(7)(+) population in the fetal liver is committed to T, NK,
      dendritic, and fetal intestinal LT producer lineage, the latter being an
      intermediate stage during differentiation of NK and dendritic cells.

PMID- 11509591
TI  - Longevity of antigen presentation and activation status of APC are decisive
      factors in the balance between CTL immunity versus tolerance.
AB  - Encounter of Ag by naive T cells can lead to T cell priming as well as tolerance.
      The balance between immunity and tolerance is controlled by the conditions of Ag
      encounter and the activation status of the APC. We have investigated the rules
      that govern this balance in case an environment that normally induces tolerance
      is reverted into a milieu that promotes T cell priming, using a minimal CTL
      epitope derived from human adenovirus type 5 E1A. Vaccination of mice s.c. with
      E1A peptide in IFA readily induces CTL tolerance, resulting in the inability to
      control E1A-expressing tumors. The present study shows that efficient CTL priming
      is achieved when this peptide vaccine is combined with systemic administration of
      APC-activating compounds like agonistic anti-CD40 mAb or polyriboinosinate
      polyribocytidylate. Surprisingly, this CTL response is not long-lasting and
      therefore fails to protect against tumor outgrowth. Disappearance of CTL
      reactivity was strongly associated with systemic persistence of the peptide for
      >200 days. In contrast, peptide administered in PBS does not persist and
      generates long term CTL immunity capable of rejecting Ad5E1A-positive tumors,
      when combined with CD40 triggering. Thus, presentation of CTL epitopes in an
      appropriate costimulatory setting by activated APC, although being essential and
      sufficient for CTL priming, eventually results in tolerance when the Ag persists
      systemically for prolonged times. These observations are important for the
      development of immune intervention schemes in autoimmunity and cancer.

PMID- 11509592
TI  - Exogenous peptides presented by transporter associated with antigen processing
      (TAP)-deficient and TAP-competent cells: intracellular loading and kinetics of
      presentation.
AB  - This study investigates the differential capacity of TAP-deficient T2 cells, TAP
      competent EBV cells, and immature and mature dendritic cells to present peptides
      to preformed CTL lines. It demonstrates that presentation of exogenous peptides
      involves peptide uptake and loading onto newly synthesized MHC class I molecules.
      This mechanism was best demonstrated for low affinity peptides in the presence of
      irrelevant peptides competing for HLA binding sites. Under these circumstances,
      inhibition of protein synthesis with cycloheximide or vesicular trafficking with
      brefeldin A significantly reduced the presentation of low affinity peptides. This
      was not restored by adding exogenous beta(2)-microglobulin to stabilize the MHC
      complex on the cell surface. In contrast, presentation of high affinity peptides
      was not sensitive to cycloheximide or brefeldin A, which suggests that different
      mechanisms may operate for presentation of high and low affinity peptides by TAP
      competent cells. High affinity peptides can apparently compete with peptides in
      preloaded MHC class I molecules at the cell surface, whereas low affinity
      peptides require empty MHC molecules within cells. Accordingly, very high
      concentrations of exogenous low affinity peptides in conjunction with active MHC
      class I metabolism were required to allow successful presentation against a
      background of competing intracellular high affinity peptides in TAP-competent
      cells. These findings have implications for the design of peptide and protein
      based vaccines.

PMID- 11509593
TI  - Neutrophils process exogenous bacteria via an alternate class I MHC processing
      pathway for presentation of peptides to T lymphocytes.
AB  - Peptides that are presented by class I MHC (MHC-I) molecules derive from
      cytosolic Ags processed via the conventional MHC-I pathway or exogenous Ags
      processed via alternate MHC-I processing mechanisms. Alternate MHC-I processing
      by macrophages and dendritic cells allows presentation of peptides from
      particulate Ags, including bacteria. Despite the established phagocytic activity
      of neutrophils, MHC-I processing and presentation of phagocytosed Ags by
      neutrophils has not been investigated. Murine neutrophils from peritoneal
      exudates were shown to express MHC-I molecules and tested for the ability to
      process HB101.Crl-OVA, Escherichia coli transfected to express a fusion protein
      containing the 257-264 epitope of OVA. Neutrophils were found to process
      HB101.Crl-OVA and present OVA(257-264)-K(b) complexes to CD8OVA T hybridoma cells
      via a pathway that was resistant to brefeldin A, an inhibitor of anterograde
      endoplasmic reticulum-Golgi transport, and lactacystin, a proteasome inhibitor.
      These results suggest that neutrophils process phagocytosed bacteria via a
      vacuolar alternate MHC-I pathway that does not involve cytosolic processing. In
      addition, neutrophils were found to secrete or "regurgitate" processed peptide
      that was subsequently presented by neighboring prefixed macrophages or dendritic
      cells. Thus, neutrophils may influence T cell responses to bacteria, either by
      directly presenting peptide-MHC-I complexes or by delivering peptides to other
      APCs for presentation. Hypothetically, neutrophils may directly present peptide
      to effector T cells in vivo at sites of inflammation, inducing cytokine
      production, whereas dendritic cells in receipt of neutrophil-derived antigenic
      peptides may migrate to lymphoid organs to initiate T cell responses.

PMID- 11509594
TI  - Bidirectional negative regulation of human T and dendritic cells by CD47 and its
      cognate receptor signal-regulator protein-alpha: down-regulation of IL-12
      responsiveness and inhibition of dendritic cell activation.
AB  - Proinflammatory molecules, including IFN-gamma and IL-12, play a crucial role in
      the elimination of causative agents. To allow healing, potent anti-inflammatory
      processes are required to down-regulate the inflammatory response. In this study,
      we first show that CD47/integrin-associated protein, a ubiquitous multispan
      transmembrane protein highly expressed on T cells, interacts with signal
      regulator protein (SIRP)-alpha, an immunoreceptor tyrosine-based inhibition motif
      containing molecule selectively expressed on myelomonocytic cells, and next
      demonstrate that this pair of molecules negatively regulates human T and
      dendritic cell (DC) function. CD47 ligation by CD47 mAb or L-SIRP-alpha
      transfectants inhibits IL-12R expression and down-regulates IL-12 responsiveness
      of activated CD4(+) and CD8(+) adult T cells without affecting their response to
      IL-2. Human CD47-Fc fusion protein binds SIRP-alpha expressed on immature DC and
      mature DC. SIRP-alpha engagement by CD47-Fc prevents the phenotypic and
      functional maturation of immature DC and still inhibits cytokine production by
      mature DC. Finally, in allogeneic MLR between mDC and naive T cells, CD47-Fc
      decreases IFN-gamma production after priming and impairs the development of a Th1
      response. Therefore, CD47 on T cells and its cognate receptor SIRP-alpha on DC
      define a novel regulatory pathway that may be involved in the maintenance of
      homeostasis by preventing the escalation of the inflammatory immune response.

PMID- 11509595
TI  - Antigen-specific blockade of T cells in vivo using dimeric MHC peptide.
AB  - Ag-specific immune tolerance in clinical organ transplantation is currently an
      unrealized but critical goal of transplant biology. The specificity and avidity
      of multimerized MHC-peptide complexes suggests their potential ability to
      modulate T cell sensitization and effector functions. In this study, we examined
      the ability of MHC-peptide dimers to modulate T cell function both in vitro and
      in vivo. Soluble MHC dimers induced modulation of surface TCR expression and
      inhibited T cell cytolytic activity at nanomolar concentrations in vitro.
      Furthermore, engagement of TCR by soluble dimers resulted in phosphorylation of
      the TCR zeta-chain and recruitment and phosphorylation of zeta-associated protein
      70 to the signaling complex, the latter of which increased upon dimer cross
      linking. Significantly, Ag-specific inhibition of an alloreactive TCR-transgenic
      T cell population in vivo resulted in consequent outgrowth of an allogeneic
      tumor. The prolonged Ag-specific suppression of expansion and/or effector
      function of cognate T cells in vivo suggests that soluble MHC dimers may be a
      means of inducing sustained Ag-specific T cell unresponsiveness in vivo.

PMID- 11509596
TI  - MHC class I allele dosage alters CD8 expression by intestinal intraepithelial
      lymphocytes.
AB  - The development of TCR alphabeta(+), CD8alphabeta(+) intestinal intraepithelial
      lymphocytes (IEL) is dependent on MHC class I molecules expressed in the thymus,
      while some CD8alphaalpha(+) IEL may arise independently of MHC class I. We
      examined the influence of MHC I allele dosage on the development CD8(+) T cells
      in RAG 2(-/-) mice expressing the H-2D(b)-restricted transgenic TCR specific for
      the male, Smcy-derived H-Y Ag (H-Y TCR). IEL in male mice heterozygous for the
      restricting (H-2D(b)) and nonrestricting (H-2D(d)) MHC class I alleles (MHC F(1))
      were composed of a mixture of CD8alphabeta(+) and CD8alphaalpha(+) T cells, while
      T cells in the spleen were mostly CD8alphabeta(+). This was unlike IEL in male
      mice homozygous for H-2D(b), which had predominantly CD8alphaalpha(+) IEL and few
      mostly CD8(-) T cells in the spleen. Our results demonstrate that deletion of
      CD8alphabeta(+) cells in H-Y TCR male mice is dependent on two copies of H-2D(b),
      whereas the generation of CD8alphaalpha(+) IEL requires only one copy. The
      existence of CD8alphabeta(+) and CD8alphaalpha(+) IEL in MHC F(1) mice suggests
      that their generation is not mutually exclusive in cells with identical TCR.
      Furthermore, our data imply that the level of the restricting MHC class I allele
      determines a threshold for conventional CD8alphabeta(+) T cell selection in the
      thymus of H-Y TCR-transgenic mice, whereas the development of CD8alphaalpha(+)
      IEL is dependent on, but less sensitive to, this MHC class I allele.

PMID- 11509597
TI  - Immune rejection of a large sarcoma following cyclophosphamide and IL-12
      treatment requires both NK and NK T cells and is associated with the induction of
      a novel NK T cell population.
AB  - Combined immunotherapy with cyclophosphamide (Cy) and IL-12, but not IL-12 alone,
      stimulates eradication of a large established solid tumor (20 mm), MCA207, a
      methylcholanthrene-induced murine sarcoma. In these studies we demonstrate that
      NK1.1(+) cells and CD1d-dependent NK T cells each play important yet distinct
      roles in regression of a large tumor in response to Cy and IL-12, and we define a
      novel NK T cell subset, selectively increased by this treatment. Mice depleted of
      NK1.1(+) cells demonstrated more rapid initial tumor growth and prolonged tumor
      regression following treatment, but tumors were eventually eradicated. In
      contrast, initial tumor regression following therapy was unimpaired in CD1d(-/-)
      mice, which are deficient in most NK T cells, but tumors recurred. No tumor
      regression occurred following Cy and IL-12 therapy in CD1d(-/-) mice that were
      depleted of NK1.1(+) cells. We found that Cy and IL-12 induced the selective
      increase in liver and spleen lymphocytes of a unique NK T subpopulation
      (DX5(+)NK1.1(-)CD3(+)). These cells were not induced by treatment in CD1d(-/-)
      mice. Our studies demonstrate a contribution of both NK and NK T cells to the Cy-
      and IL-12-stimulated anti-tumor response. We describe the selective induction of
      a distinct NK T cell subset by Cy and IL-12 therapy, not seen following IL-12
      therapy alone, which we suggest may contribute to the successful anti-tumor
      response induced by this immunotherapeutic regimen.

PMID- 11509598
TI  - Peptide requirement for CTL activation reflects the sensitivity to CD3
      engagement: correlation with CD8alphabeta versus CD8alphaalpha expression.
AB  - In our previous studies, CTL that were sensitive to low concentrations of peptide
      Ag were found to be far superior to those requiring high concentrations of Ag for
      reducing viral burden when adoptively transferred into SCID mice. Thus it is
      important that we understand the mechanisms that control the requirement for
      peptide Ag with the long-term goal of selectively expanding these exquisitely
      sensitive cells in vivo. Although TCR affinity is one parameter that can affect
      the CTL sensitivity for Ag, we investigated whether additional mechanisms may
      also be involved. In studies using a TCR transgenic mouse model, we successfully
      generated CTL with identical TCR affinity that possess distinctly different
      activation requirements. Using both peptide Ag and anti-CD3 Ab to activate the
      CTL lines of high vs low avidity, we found that the variations in activation
      threshold are the result of differences in the required number of engaged TCR.
      Additionally, we have observed that the ratio of CD8alphabeta to CD8alphaalpha is
      significantly greater in CTL lines that are more sensitive to TCR engagement,
      which may contribute to the lower activation threshold of these CTL following CD3
      engagement. These studies identify a novel mechanism by which the activation
      requirements of Ag-specific CTL are determined by demonstrating a direct
      correlation between the sensitivity to TCR engagement, the expression of levels
      CD8alphabeta vs alphaalpha, and the amount of peptide Ag required to reach the
      threshold for activation.

PMID- 11509599
TI  - Neonatal immunity develops in a transgenic TCR transfer model and reveals a
      requirement for elevated cell input to achieve organ-specific responses.
AB  - In recent years, it has become clear that neonatal exposure to Ag induces rather
      than ablates T cell immunity. Moreover, rechallenge with the Ag at adult age can
      trigger secondary responses that are distinct in the lymph node vs the spleen.
      The question addressed in this report is whether organ-specific secondary
      responses occur as a result of the diversity of the T cell repertoire or could
      they arise with homogeneous TCR-transgenic T cells. To test this premise, we used
      the OVA-specific DO11.10 TCR-transgenic T cells and established a neonatal T cell
      transfer system suitable for these investigations. In this system, neonatal T
      cells transferred from 1-day-old DO11.10/SCID mice into newborn (1-day-old)
      BALB/c mice migrate to the host's spleen and maintain stable frequency. The
      newborn BALB/c hosts were then given Ig-OVA, an Ig molecule carrying the OVA
      peptide, and challenged with the OVA peptide in CFA at the age of 7 wk; then
      their secondary responses were analyzed. The findings show that the lymph node T
      cells were deviated and produced IL-4 instead of IFN-gamma and the splenic T
      cells, although unable to proliferate or produce IFN-gamma, secreted a
      significant level of IL-2. Supply of exogenous IL-12 during Ag stimulation
      restores both proliferation and IFN-gamma production by the splenic T cells. This
      restorable form of splenic unresponsiveness referred to as IFN-gamma-dependent
      anergy required a transfer of a high number of neonatal DO11.10/SCID T cells to
      develop. Thus, the frequency of neonatal T cell precursors rather than repertoire
      diversity exerts control on the development of organ-specific neonatal immunity.

PMID- 11509600
TI  - Inhibition of activated/memory (CD45RO(+)) T cells by oxidative stress associated
      with block of NF-kappaB activation.
AB  - Impaired immune responses in cancer patients have been associated with oxidative
      stress. Increased levels of reactive oxygen species released from activated,
      tumor-infiltrating macrophages or granulocytes may therefore constitute a hurdle
      for effective immunotherapy against cancer. In this study, we investigated
      functional consequences and molecular events in T cells exposed to low levels of
      oxidative stress. We observed that cytokine production of human PBMC, upon
      stimulation with an HLA-A*0201-restricted influenza peptide and nonspecific
      receptor cross-linking, was reduced after exposure to micromolar levels of H2O2.
      Functional impairment as measured by IFN-gamma release occurred earlier and at
      lower doses of exogenously added H2O2 than required to induce apoptosis. This
      suggests that there is a dose window of oxidative stress leading to T cell
      unresponsiveness in the absence of apoptosis. The reduction of Th1 cytokines,
      induced by H2O2, was predominantly observed in memory/effector (CD45RO(+)) T
      cells and correlated with a block in NF-kappaB activation. IL-10 production was
      more profoundly influenced by low doses of H2O2 than IFN-gamma, TNF-alpha, and IL
      2. The influence of H2O2 on production of IL-10 was not significantly different
      between memory/activated and naive T cells. These observations suggest that Th1
      and Th2 cytokines are differently regulated under conditions of oxidative stress.
      Taken together, these findings may explain why Ag-experienced, CD45RO(+), T cells
      found in the tumor milieu are functionally suppressed.

PMID- 11509601
TI  - Genomic DNA released by dying cells induces the maturation of APCs.
AB  - Mature APCs play a key role in the induction of Ag-specific immunity. This work
      examines whether genomic DNA released by dying cells provides a stimulus for APC
      maturation. Double-stranded but not single-stranded genomic DNA triggered APC to
      up-regulate expression of MHC class I/II and various costimulatory molecules.
      Functionally, dsDNA enhanced APC function in vitro and improved primary cellular
      and humoral immune responses in vivo. These effects were dependent on the length
      and concentration of the dsDNA but were independent of nucleotide sequence. The
      maturation of APC induced by dsDNA may promote host survival by improving immune
      surveillance at sites of tissue injury/infection.

PMID- 11509602
TI  - Regulation of IL-12 p40 promoter activity in primary human monocytes: roles of NF
      kappaB, CCAAT/enhancer-binding protein beta, and PU.1 and identification of a
      novel repressor element (GA-12) that responds to IL-4 and prostaglandin E(2).
AB  - Appropriate regulation of IL-12 expression is critical for cell-mediated immune
      responses. In the present study, we have analyzed the regulation of IL-12 p40
      promoter activity in primary human monocytes in vivo. Accordingly, we analyzed
      the p40 promoter by in vivo footprinting in resting and activated primary human
      blood CD14(+) monocytes. Interestingly, footprints at binding sites for trans
      activating proteins such as C/EBP, NF-kappaB, and ETS were only found upon
      stimulation with LPS and IFN-gamma. In contrast, a footprint over a purine-rich
      sequence at -155, termed GA-12 (GATA sequence in the IL-12 promoter), was
      observed in resting, but not activated, cells. Further characterization of this
      site revealed specific complex formation at a protected GATA core motif in
      unstimulated primary monocytes and RAW264.7 macrophages. Mutagenesis within the
      GA-12 sequence caused a significant up-regulation of inducible IL-12 p40 promoter
      activity in both transient and stable transfection systems, suggesting a
      repressor function of this site. Furthermore, binding activity of the GA-12
      binding protein GAP-12 was increased by treatment with two potent inhibitors of
      IL-12 expression, IL-4 and PGE(2). Finally, we observed that IL-4-mediated
      repression of IL-12 p40 promoter activity is critically dependent on an intact GA
      12 sequence. In summary, our data underline the complex regulation of the human
      IL-12 p40 promoter and identify GA-12 as a potent, novel repressor element that
      mediates IL-4-dependent suppression of inducible promoter activity in monocytes.
      Regulation of GAP-12 binding may thus modulate IL-12 p40 gene expression.

PMID- 11509603
TI  - The recognition of HLA-B27 by human CD4(+) T lymphocytes.
AB  - HLA-B27 transgenic animal models suggest a role for CD4(+) T lymphocytes in the
      pathogenesis of the spondyloarthropathies, and murine studies have raised the
      possibility that unusual forms of B27 may be involved in disease. We demonstrate
      that CD4(+) T cells capable of recognizing B27 can be isolated from humans by
      coculture with the MHC class II-negative cell line T2 transfected with B27. These
      CD4(+) T cells recognize a panel of B27-transfected cell lines that are defective
      in Ag-processing pathways, but not the nontransfected parental cell lines, in a
      CD4-dependent fashion. Inhibition of responses by the MHC class I-specific mAb
      w6/32 and the B27 binding mAb ME1 implicates the recognition of a form of B27
      recognized by both of these Abs. We suggest that B27-reactive CD4(+) T cells may
      be pathogenic in spondyloarthropathies, particularly if factors such as infection
      influence expression of abnormal forms of B27.

PMID- 11509604
TI  - Connection between B lymphocyte and osteoclast differentiation pathways.
AB  - Osteoclasts differentiate from the hemopoietic monocyte/macrophage cell lineage
      in bone marrow through cell-cell interactions between osteoclast progenitors and
      stromal/osteoblastic cells. Here we show another osteoclast differentiation
      pathway closely connected with B lymphocyte differentiation. Recently the TNF
      family molecule osteoclast differentiation factor/receptor activator of NF-kappaB
      ligand (ODF/RANKL) was identified as a key membrane-associated factor regulating
      osteoclast differentiation. We demonstrate that B-lymphoid lineage cells are a
      major source of endogenous ODF/RANKL in bone marrow and support osteoclast
      differentiation in vitro. In addition, B-lymphoid lineage cells in earlier
      developmental stages may hold a potential to differentiate into osteoclasts when
      stimulated with M-CSF and soluble ODF/RANKL in vitro. B-lymphoid lineage cells
      may participate in osteoclastogenesis in two ways: they 1) express ODF/RANKL to
      support osteoclast differentiation, and 2) serve themselves as osteoclast
      progenitors. Consistent with these observations in vitro, a decrease in
      osteoclasts is associated with a decrease in B-lymphoid cells in klotho mutant
      mice (KL(-/-)), a mouse model for human aging that exhibits reduced turnover
      during bone metabolism, rather than a decrease in the differentiation potential
      of osteoclast progenitors. Taken together, B-lymphoid lineage cells may affect
      the pathophysiology of bone disorders through regulating osteoclastogenesis.

PMID- 11509605
TI  - Efficient presentation of both cytosolic and endogenous transmembrane protein
      antigens on MHC class II is dependent on cytoplasmic proteolysis.
AB  - Peptides from extracellular proteins presented on MHC class II are mostly
      generated and loaded in endolysosomal compartments, but the major pathways
      responsible for loading peptides from APC-endogenous sources on MHC class II are
      as yet unclear. In this study, we show that MHC class II molecules present
      peptides from proteins such as OVA or conalbumin introduced into the cytoplasm by
      hyperosmotic pinosome lysis, with efficiencies comparable to their presentation
      via extracellular fluid-phase endocytosis. This cytosolic presentation pathway is
      sensitive to proteasomal inhibitors, whereas the presentation of exogenous Ags
      taken up by endocytosis is not. Inhibitors of nonproteasomal cytosolic proteases
      can also inhibit MHC class II-restricted presentation of cytosolically delivered
      protein, without inhibiting MHC class I-restricted presentation from the same
      protein. Cytosolic processing of a soluble fusion protein containing the peptide
      epitope I-Ealpha(52-68) yields an epitope that is similar to the one generated
      during constitutive presentation of I-Ealpha as an endogenous transmembrane
      protein, but is subtly different from the one generated in the exogenous pathway.
      Constitutive MHC class II-mediated presentation of the endogenous transmembrane
      protein I-Ealpha is also specifically inhibited over time by inhibitors of
      cytosolic proteolysis. Thus, Ag processing in the cytoplasm appears to be
      essential for the efficient presentation of endogenous proteins, even
      transmembrane ones, on MHC class II, and the proteolytic pathways involved may
      differ from those used for MHC class I-mediated presentation.

PMID- 11509606
TI  - Cellular localization and functional role of phosphatidylcholine-specific
      phospholipase C in NK cells.
AB  - Although several classes of phospholipases have been implicated in NK cell
      mediated cytotoxicity, no evidence has been reported to date on involvement of
      phosphatidylcholine-specific phospholipase C (PC-PLC) in NK activation by
      lymphokines and/or in lytic granule exocytosis. This study demonstrated the
      expression of two PC-PLC isoforms (M(r) 40 and 66 kDa) and their IL-2-dependent
      distribution between cytoplasm and ectoplasmic membrane surface in human NK
      cells. Following cell activation by IL-2, cytoplasmic PC-PLC translocated from
      the microtubule-organizing center toward cell periphery, essentially by kinesin
      supported transport along microtubules, while PC-PLC exposed on the outer cell
      surface increased 2-fold. Preincubation of NK cells with a PC-PLC inhibitor,
      tricyclodecan-9-yl-xanthogenate, strongly reduced NK-mediated cytotoxicity. In IL
      2-activated cells, this loss of cytotoxicity was associated with a decrease of PC
      PLC exposed on the cell surface, and accumulation of cytoplasmic PC-PLC in the
      Golgi region. Massive colocalization of PC-PLC-rich particles with perforin
      containing granules was found in the cytoplasm of NK-activated (but not NK
      resting) cells; both organelles clustered at the intercellular contact region of
      effector-target cell conjugates. These newly detected mechanisms of PC-PLC
      translocation and function support an essential role of this enzyme in regulated
      granule exocytosis and NK-mediated cytotoxicity.

PMID- 11509607
TI  - Intestinal macrophages lack CD14 and CD89 and consequently are down-regulated for
      LPS- and IgA-mediated activities.
AB  - The intestinal mucosa normally displays minimal inflammation despite the close
      proximity between mucosal macrophages and lumenal bacteria. Macrophages interact
      with bacteria and their products through CD14, a surface receptor involved in the
      response to LPS, and CD89, the receptor for IgA (FcalphaR). Here we show that
      resident macrophages isolated from normal human intestine lack CD14 and CD89. The
      absence of CD14 and CD89 was not due to the isolation procedure or mucosal cell
      products, but was evident at the transcriptional level, as the macrophages
      expressed neither CD14- nor CD89-specific mRNAs, but did express Toll-like
      receptor 2 and 4 transcripts. Consistent with their CD14(-) phenotype, lamina
      propria macrophages displayed markedly reduced LPS-induced cytokine production
      and LPS-enhanced phagocytosis. In addition, IgA-enhanced phagocytosis was sharply
      reduced in lamina propria macrophages. Thus, the absence of CD14 and CD89 on
      resident intestinal macrophages, due to down-regulated gene transcription, causes
      down-modulated LPS- and IgA-mediated functions and probably contributes to the
      low level of inflammation in normal human intestinal mucosa.

PMID- 11509608
TI  - Abnormal T cell receptor signal transduction of CD4 Th cells in X-linked
      lymphoproliferative syndrome.
AB  - The molecular basis of X-linked lymphoproliferative (XLP) disease has been
      attributed to mutations in the signaling lymphocytic activation molecule
      associated protein (SAP), an src homology 2 domain-containing intracellular
      signaling molecule known to interact with the lymphocyte-activating surface
      receptors signaling lymphocytic activation molecule and 2B4. To investigate the
      effect of SAP defects on TCR signal transduction, herpesvirus saimiri
      immortalized CD4 Th cells from XLP patients and normal healthy individuals were
      examined for their response to TCR stimulation. CD4 T cells of XLP patients
      displayed elevated levels of tyrosine phosphorylation compared with CD4 T cells
      from healthy individuals. In addition, downstream serine/threonine kinases are
      constitutively active in CD4 T cells of XLP patients. In contrast, TCR-mediated
      activation of Akt, c-Jun-NH(2)-terminal kinases, and extracellular signal
      regulated kinases in XLP CD4 T cells was transient and rapidly diminished when
      compared with that in control CD4 T cells. Consequently, XLP CD4 T cells
      exhibited severe defects in up-regulation of IL-2 and IFN-gamma cytokine
      production upon TCR stimulation and in MLRs. Finally, SAP specifically interacted
      with a 75-kDa tyrosine-phosphorylated protein upon TCR stimulation. These results
      demonstrate that CD4 T cells from XLP patients exhibit aberrant TCR signal
      transduction and that the defect in SAP function is likely responsible for this
      phenotype.

PMID- 11509609
TI  - Regulatory potential of fever-range whole body hyperthermia on Langerhans cells
      and lymphocytes in an antigen-dependent cellular immune response.
AB  - The febrile response is one of the most common features of infection and
      inflammation. However, temperature is rarely a variable in experimental
      immunological investigations. To determine whether the thermal microenvironment
      has any immunoregulatory potential in an Ag-dependent response, we applied a mild
      fever-range whole body hyperthermia (FR-WBH) protocol to BALB/c mice experiencing
      the contact hypersensitivity (CHS) reaction. We observed that the timing of this
      FR-WBH treatment relative to the different phases of the CHS response was crucial
      to the outcome. FR-WBH treatment before sensitization with a 0.5% FITC solution
      resulted in a depressed CHS response. This appears to be due to direct effects of
      FR-WBH on epidermal Langerhans cell trafficking to the draining lymph nodes. In
      contrast, application of FR-WBH directly after application of the elicitation
      dose of FITC solution resulted in an enhanced reaction. This result correlates
      with increased homing of lymphocytes to the site of elicitation. Overall, these
      data have important implications regarding the role of thermal changes
      experienced during infection and the clinical use of FR-WBH relative to
      immunotherapeutic strategies.

PMID- 11509610
TI  - Progressive depletion of peripheral B lymphocytes in 4-1BB (CD137) ligand/I
      Ealpha)-transgenic mice.
AB  - Interaction of 4-1BB (CD137) and its ligand (4-1BBL) is thought to positively
      regulate cell-mediated and humoral immune responses. We have prepared transgenic
      mouse strains that express 4-1BBL cDNA under the control of MHC class II I-Ealpha
      promoter. The 4-1BBL-transgenic mice show progressive splenomegaly and selective
      depletion of B220(+) B cells accompanied with low levels of circulating IgG and
      defective humoral responses to Ag challenge. In addition, splenocytes from the
      transgenic mice fail to provide stimulation for allogeneic T cells in both
      lymphoproliferative and CTL responses in vitro, whereas their T cells remain
      functionally normal. Our results reveal unexpected functions of 4-1BBL in the
      regulation of humoral immune responses and Ag presentation.

PMID- 11509611
TI  - Inhibition of NFATx activation by an oligopeptide: disrupting the interaction of
      NFATx with calcineurin.
AB  - Calcium-dependent phosphatase calcineurin (CN) regulates the activation and
      nuclear translocation of NFAT. We identify here a novel CN-binding motif in one
      member of the NFAT family, NFATx, and a peptide based on this motif, Pep3. Pep3
      binds CN and competes with wild-type NFATx for CN interaction. Amino acid
      mutations within Pep3 show that multiple amino acid residues are required for the
      effective functions of Pep3. Ectopic expression of Pep3 in a Th clone via a
      retrovirus-mediated gene transfer could selectively block the nuclear
      translocation of endogenous NFATx, whereas it had little effect on the nuclear
      translocation of another member of the NFAT family, NFATp. Furthermore, in
      transfection experiments, Pep3 also blocked the nuclear translocation of
      transfected NFATx, but not NFATp, in the B cell line M12, demonstrating specific
      inhibition of Pep3 for NFATx. Importantly, several cytokines produced by the T
      cell clone were severely repressed by ectopic Pep3, and indeed, the production of
      these cytokines was enhanced by the expression of wild-type NFATx. Our results
      show selective inhibition of NFATx activation and cytokine expression by Pep3 and
      suggest a new approach for studying the biology of each NFAT family member. This
      approach may provide an opportunity for pharmacological targeting of Ca(2+)
      dependent signaling events.

PMID- 11509612
TI  - Immunomodulation of experimental autoimmune encephalomyelitis with ordered
      peptides based on MHC-TCR binding motifs.
AB  - T cell-mediated destruction of the myelin sheath causes inflammatory damage of
      the CNS in multiple sclerosis (MS). The major T and B cell responses in MS
      patients who are HLA-DR2 (about two-thirds of MS patients) react to a region
      between residues 84 and 103 of myelin basic protein (1 ). The crystal structure
      of HLA-DR2 complexed with myelin basic protein(84-102) confirmed that Lys(91) is
      the major TCR contact site, whereas Phe(90) is a major anchor to MHC and binds
      the hydrophobic P4 pocket (2 ). We have tested peptides containing repetitive 4
      aa sequences designed to bind critical MHC pockets and to interfere with T cell
      activation. One such sequence, EYYKEYYKEYYK, ameliorates experimental autoimmune
      encephalomyelitis in Lewis rats, an animal model of MS.

PMID- 11509614
TI  - Negative regulation of the NFAT1 factor by CD45: implication in HIV-1 long
      terminal repeat activation.
AB  - HIV-1 gene regulation is greatly dependent on the presence of the -104/-81
      enhancer region which is regulated by both NF-kappaB and NFAT transcription
      factors. We have found that a greater induction in HIV-1 long terminal repeat
      driven gene expression was observed upon PMA/ionomycin (Iono) stimulation of a
      CD45-deficient cell line (J45.01) in comparison to the parental Jurkat cells.
      Unlike NF-kappaB which was not affected by the absence of CD45, NFAT showed a
      much greater augmentation in nuclear translocation and transcriptional activity
      in J45.01 cells upon PMA/Iono stimulation. PMA/Iono-induced NFAT activation, NFAT
      translocation and calcium influx peaked at similar time points for both Jurkat
      and J45.01 cell lines. The NFAT-dependent promoters from the IL-2 and TNF-alpha
      genes were also more potently activated by PMA/Iono in J45.01 cells.
      Interestingly, higher levels of intracellular calcium were consistently
      demonstrated in PMA/Iono-induced CD45-deficient cell lines (J45.01 and HPB45.0).
      Furthermore, PMA/Iono induction of calcium mobilization in both Jurkat and J45.01
      cell lines was observed to be EGTA-sensitive. Mechanistic studies revealed that
      CD3zeta and ZAP-70 were more heavily tyrosine phosphorylated in J45.01 cells than
      Jurkat cells. Analysis of the HIV-1 enhancer by EMSAs demonstrated that the bound
      NFAT complex was present at higher levels in J45.01 nuclear extracts and that the
      NFAT1 member was predominant. In conclusion, our results indicate that NFAT
      activation by stimuli acting in a more distal fashion from the TCR-mediated
      signaling pathway can be down-regulated by CD45 and that this CD45-dependent
      regulation in turn affects HIV-1 long terminal repeat activation.

PMID- 11509613
TI  - Identification, cloning, and recombinant expression of procalin, a major
      triatomine allergen.
AB  - Among the most frequent anaphylactic reactions to insects are those attributed to
      reduviid bugs. We report the purification and identification of the major
      salivary allergen of these insects. This 20-kDa protein (procalin) is a member of
      the lipocalin family, which includes salivary allergens from other invertebrates
      and mammals. An expression system capable of producing reagent quantities of
      recombinant allergen was developed in Saccharomyces cerevisiae. Antisera produced
      against recombinant protein cross-reacts with ELISA with salivary allergen.
      Recombinant Ag is also shown to react with sera from an allergic patient but not
      with control sera. By immunolocalization, the source of the salivary Ag is the
      salivary gland epithelium and its secretions.

PMID- 11509615
TI  - Phosphatidylinositol 3-kinase potentiates, but does not trigger, T cell
      proliferation mediated by the IL-2 receptor.
AB  - Proliferative signaling by the IL-2R can occur through two distinct pathways, one
      mediated by Stat5 and one by the adaptor protein Shc. Although Stat5 induces T
      cell proliferation by serving as a transcription factor, the mechanism of
      proliferative signaling by Shc is poorly defined. We examined the roles of two
      major signaling pathways downstream of Shc, the p44/p42 mitogen-activated protein
      kinase (extracellular signal-related kinase (Erk)) and phosphatidylinositol 3
      kinase (PI3K) pathways, in promitogenic gene induction and proliferation in the
      IL-2-dependent T cell line CTLL-2. Using IL-2R mutants and specific pharmacologic
      inhibitors, we found that the PI3K, but not Erk, pathway is required for maximal
      induction of c-myc, cyclin D2, cyclin D3, cyclin E, and bcl-x(L) by Shc. To test
      whether the PI3K pathway is sufficient for proliferative signaling, a tamoxifen
      regulated form of PI3K (mp110*ER) was expressed in CTLL-2 cells. Activation of
      the PI3K pathway through mp110*ER failed to up-regulate expression of the c-myc,
      cyclin D2, cyclin D3, cyclin E, bcl-2, or bcl-x(L) genes or down-regulate
      expression of p27(Kip1), even when coactivated with the Janus kinases (Jak) or
      the Raf/Erk pathway. Moreover, mp110*ER induced modest levels of thymidine
      incorporation without subsequent cell division. Although insufficient for
      mitogenesis, mp110*ER enhanced Stat5-mediated proliferative signaling through a
      mechanism independent of Stat5 transcriptional activity. Thus, in addition to
      serving a necessary, but insufficient role in Shc-mediated promitogenic gene
      expression, the PI3K pathway contributes to T cell proliferation by potentiating
      mitogenic signaling by Stat5.

PMID- 11509616
TI  - Monomorphic molecules function as additional recognition structures on haptenated
      target cells for HLA-A1-restricted, hapten-specific CTL.
AB  - Hapten-specific T cells have been shown to recognize haptenated peptides with
      high avidity and, in some instances, with promiscuous MHC restriction. In this
      study, the impact of Ag density on MHC restriction of a CTL response specific to
      the trinitrophenyl (TNP) hapten was investigated. In this study, we demonstrate a
      novel recognition mechanism used by TNP-specific CD8(+) CTL in the presence of
      high Ag doses. Although low levels of TNP epitopes on target cells allowed for
      HLA-A1-restricted CTL activity only, entirely MHC-independent target cell
      recognition became operative at high TNP loading. In both cases, recognition was
      mediated by the TCR. This MHC-independent recognition is target cell type
      restricted and critically involves in our model direct recognition of the
      ectonucleotidase family surface molecule CD39 by the CTL.

PMID- 11509617
TI  - CD4(+) and CD8(+) T cells kill intracellular Mycobacterium tuberculosis by a
      perforin and Fas/Fas ligand-independent mechanism.
AB  - Cytotoxic effector phenotype and function of MHC-restricted Mycobacterium
      tuberculosis (MTB)-reactive CD4(+) and CD8(+) T lymphocytes were analyzed from
      healthy tuberculin skin test-positive persons. After stimulation in vitro with
      MTB, both CD4(+) and CD8(+) T cells up-regulated mRNA expression for granzyme A
      and B, granulysin, perforin, and CD95L (Fas ligand). mRNA levels for these
      molecules were greater for resting CD8(+) than CD4(+) T cells. After MTB
      stimulation, mRNA levels were similar for both T cell subsets. Increased perforin
      and granulysin protein expression was confirmed in both in CD4(+) and CD8(+) T
      cells by flow cytometry. Both T cell subsets lysed MTB-infected monocytes.
      Biochemical inhibition of the granule exocytosis pathway in CD4(+) and CD8(+) T
      cells decreased cytolytic function by >90% in both T cell subsets. Ab blockade of
      the CD95-CD95L interaction decreased cytolytic function for both T cell
      populations by 25%. CD4(+) and CD8(+) T cells inhibited growth of intracellular
      MTB in autologous monocytes by 74% and 84%, respectively. However, inhibition of
      perforin activity, the CD95-CD95L interaction, or both CTL mechanisms did not
      affect CD4(+) and CD8(+) T cell mediated restriction of MTB growth. Thus,
      perforin and CD95-CD95L were not involved in CD4(+) and CD8(+) T cell mediated
      restriction of MTB growth.

PMID- 11509618
TI  - Vpr is preferentially targeted by CTL during HIV-1 infection.
AB  - The HIV-1 accessory proteins Vpr, Vpu, and Vif are essential for viral
      replication, and their cytoplasmic production suggests that they should be
      processed for recognition by CTLs. However, the extent to which these proteins
      are targeted in natural infection, as well as precise CTL epitopes within them,
      remains to be defined. In this study, CTL responses against HIV-1 Vpr, Vpu, and
      Vif were analyzed in 60 HIV-1-infected individuals and 10 HIV-1-negative controls
      using overlapping peptides spanning the entire proteins. Peptide-specific IFN
      gamma production was measured by ELISPOT assay and flow-based intracellular
      cytokine quantification. HLA class I restriction and cytotoxic activity were
      confirmed after isolation of peptide-specific CD8(+) T cell lines. CD8(+) T cell
      responses against Vpr, Vpu, and Vif were found in 45%, 2%, and 33% of HIV-1
      infected individuals, respectively. Multiple CTL epitopes were identified in
      functionally important regions of HIV-1 Vpr and Vif. Moreover, in infected
      individuals in whom the breadth of HIV-1-specific responses was assessed
      comprehensively, Vpr and p17 were the most preferentially targeted proteins per
      unit length by CD8(+) T cells. These data indicate that despite the small size of
      these proteins Vif and Vpr are frequently targeted by CTL in natural HIV-1
      infection and contribute importantly to the total HIV-1-specific CD8(+) T cell
      responses. These findings will be important in evaluating the specificity and
      breadth of immune responses during acute and chronic infection, and in the design
      and testing of candidate HIV vaccines.

PMID- 11509619
TI  - Concurrent naive and memory CD8(+) T cell responses to an influenza A virus.
AB  - Memory Thy-1(+)CD8(+) T cells specific for the influenza A virus nucleoprotein
      (NP(366-374)) peptide were sorted after staining with the D(b)NP(366) tetramer,
      labeled with CFSE, and transferred into normal Thy-1.2(+) recipients. The donor
      D(b)NP(366)(+) T cells recovered 2 days later from the spleens of the Thy-1.2(+)
      hosts showed the CD62L(low)CD44(high)CD69(low) phenotype, characteristic of the
      population analyzed before transfer, and were present at frequencies equivalent
      to those detected previously in mice primed once by a single exposure to an
      influenza A virus. Analysis of CFSE-staining profiles established that resting
      tetramer(+) T cells divided slowly over the next 30 days, while the numbers in
      the spleen decreased about 3-fold. Intranasal infection shortly after cell
      transfer with a noncross-reactive influenza B virus induced some of the donor
      D(b)NP(366)(+) T cells to cycle, but there was no increase in the total number of
      transferred cells. By contrast, comparable challenge with an influenza A virus
      caused substantial clonal expansion, and loss of the CFSE label. Unexpectedly,
      the recruitment of naive Thy-1.2(+)CD8(+)D(b)NP(366)(+) host D(b)NP(366)(+) T
      cells following influenza A challenge was not obviously diminished by the
      presence of the memory Thy-1.1(+)CD8(+)D(b)NP(366)(+) donor D(b)NP(366)(+) set.
      Furthermore, the splenic response to an epitope (D(b)PA(224)) derived from the
      influenza acid polymerase (PA(224-233)) was significantly enhanced in the mice
      given the donor D(b)NP(366)(+) memory population. These experiments indicate that
      an apparent recall response may be comprised of both naive and memory CD8(+) T
      cells.

PMID- 11509620
TI  - Critical role of lipopolysaccharide-binding protein and CD14 in immune responses
      against gram-negative bacteria.
AB  - LPS-binding protein (LBP) and CD14 potentiate cell activation by LPS,
      contributing to lethal endotoxemia. We analyzed the contribution of LBP/CD14 in
      models of bacterial infection. Mice pretreated with mAbs neutralizing CD14 or LBP
      showed a delay in TNF-alpha production and died of overwhelming infection within
      24 h, after a challenge with 250 CFU of virulent Klebsiella pneumoniae. Blockade
      of TNF-alpha also increased lethality, whereas pretreatment with TNF-alpha
      protected mice, even in the presence of LBP and CD14 blockade. Anti-LBP or anti
      CD14 mAbs did not improve or decrease lethality with a higher inoculum (10(5) K.
      pneumoniae) and did not affect outcome following injections of low or high
      inocula of Escherichia coli O111. These results point to the essential role of
      LBP/CD14 in innate immunity against virulent bacteria.

PMID- 11509621
TI  - HIV-1 Tat induces microvascular endothelial apoptosis through caspase activation.
AB  - HIV-1 Tat, in addition to its critical role in viral transcription, is secreted
      from infected cells and can act as a proto-cytokine. We studied the effects of
      HIV-1 Tat in primary human microvascular endothelial cells of lung origin and
      found that it caused apoptosis. This apoptosis occurred without induction of
      either Fas or TNF, known mediators of programmed cell death. Tat, like Fas
      ligand, induced cleavage of chromatin structure, as evidenced by changes in DNA
      laddering, incorporation of fluorescein into the nicked chromosomal DNA (TUNEL
      assay), and mono- or oligonucleosomes. Furthermore, Tat treatment caused cleavage
      of poly(A/DP)-ribose polymerase, a substrate of caspases. Caspase-3, but not
      caspase-9, was activated following treatment of primary human microvascular
      endothelial cells of lung origin with either Tat or anti-Fas agonist Ab (anti
      Fas). Inhibition of caspase-3 activity markedly reduced apoptosis. Although Fas
      mediated apoptosis involved changes in Bcl-2, Bax, and Bad regulatory proteins,
      such alterations were not observed with Tat. Taken together, these data
      demonstrate that HIV-1 Tat is able to activate apoptosis in microvascular
      endothelium by a mechanism distinct from TNF secretion or the Fas pathway.

PMID- 11509622
TI  - Lipoxin A(4) and aspirin-triggered 15-epi-lipoxin A(4) antagonize TNF-alpha
      stimulated neutrophil-enterocyte interactions in vitro and attenuate TNF-alpha
      induced chemokine release and colonocyte apoptosis in human intestinal mucosa ex
      vivo.
AB  - Lipoxins (LXs) are lipoxygenase-derived eicosanoids and putative endogenous
      braking signals for inflammation in the gastrointestinal tract and other organs.
      Aspirin triggers the production of 15-epimers during cell-cell interaction in a
      cytokine-primed milieu, and aspirin-triggered 15-epi-5(S),6(R),15(S)-trihydroxy
      7,9,13-trans-11-cis-eicosatetraenoic acid (15-epi-LXA(4)) may contribute to the
      bioactivity profile of this prototype nonsteroidal anti-inflammatory drug in
      vivo. We determined the effect of LXA(4), 15-(R/S)-methyl-11,12-dehydro-LXA(4)
      methyl ester (15-(R/S)-methyl-LXA(4)), and stable analogs of LXA(4) on TNF-alpha
      stimulated neutrophil-enterocyte interaction in vitro and TNF-alpha-stimulated
      chemokine release, changes in mucosal architecture, and enterocyte apoptosis in
      cytokine-activated intact human colonic mucosa ex vivo. LXA(4), 15-(R/S)-epi
      LXA(4), and 16-phenoxy-11,12-dehydro-17,18,19,20-tetranor-LXA(4) methyl ester (16
      phenoxy-LXA(4)) inhibited TNF-alpha-stimulated neutrophil adherence to epithelial
      monolayers at nanomolar concentrations. In parallel experiments involving human
      colonic mucosa ex vivo, LXA(4)potently attenuated TNF-alpha-stimulated release of
      the C-X-C chemokine IL-8, and the C-C chemokines monocyte-chemoattractant protein
      1 (MCP-1) and RANTES. Exposure of strips of normal human colonic mucosa to TNF
      alpha induced disruption of mucosa architecture and enhanced colonocyte apoptosis
      via a caspase-3-independent mechanism. Prior exposure of the mucosa strips to 15
      (R/S)-methyl-LXA(4) attenuated TNF-alpha-stimulated colonocyte apoptosis and
      protected the mucosa against TNF-alpha-induced mucosal damage. In aggregate, our
      data demonstrate that lipoxins and aspirin-triggered 15-epi-LXA(4) are potent
      antagonists of TNF-alpha-mediated neutrophil-enterocyte interactions in vitro,
      attenuate TNF-alpha-triggered chemokine release and colonocyte apoptosis, and are
      protective against TNF-alpha-induced morphological disruption in human colonic
      strips ex vivo. Our observations further expand the anti-inflammatory profile of
      these lipoxygenase-derived eicosanoids and suggest new therapeutic approaches for
      the treatment of inflammatory bowel disease.

PMID- 11509623
TI  - Elimination of colonic patches with lymphotoxin beta receptor-Ig prevents Th2
      cell-type colitis.
AB  - Past studies have shown that colonic patches, which are the gut-associated
      lymphoreticular tissues (GALT) in the colon, become much more pronounced in
      hapten-induced murine colitis, and this was associated with Th2-type T cell
      responses. To address the role of GALT in colonic inflammation, experimental
      colitis was induced in mice either lacking organized GALT or with altered GALT
      structures. Trinitrobenzene sulfonic acid was used to induce colitis in mice
      given lymphotoxin-beta receptor-Ig fusion protein (LTbetaR-Ig) in utero, a
      treatment that blocked the formation of both Peyer's and colonic patches. Mice
      deficient in colonic patches developed focal acute ulcers with Th1-type
      responses, whereas lesions in normal mice were of a diffuse mucosal type with
      both Th1- and Th2-type cytokine production. We next determined whether LTbetaR-Ig
      could be used to treat colitis in normal or Th2-dominant, IFN-gamma gene knockout
      (IFN-gamma(-/-)) mice. Four weekly treatments with LTbetaR-Ig resulted in
      deletion of Peyer's and colonic patches with significant decreases in numbers of
      dendritic cells. This pretreatment protected IFN-gamma(-/-) mice from
      trinitrobenzene sulfonic acid-induced colitis; however, in normal mice this
      weekly treatment was less protective. In these mice hypertrophy of colonic
      patches was seen after induction of colitis. We conclude that Th2-type colitis is
      dependent upon the presence of colonic patches. The effect of LTbetaR-Ig was
      mediated through prevention of colonic patch hypertrophy in the absence of IFN
      gamma. Thus, LTbetaR-Ig may offer a possible treatment for the Th2-dominant form
      of colitis.

PMID- 11509624
TI  - Increased susceptibility of decay-accelerating factor deficient mice to anti
      glomerular basement membrane glomerulonephritis.
AB  - To prevent complement-mediated autologous tissue damage, host cells express a
      number of membrane-bound complement inhibitors. Decay-accelerating factor (DAF,
      CD55) is a GPI-linked membrane complement regulator that is widely expressed in
      mammalian tissues including the kidney. DAF inhibits the C3 convertase of both
      the classical and alternative pathways. Although DAF deficiency contributes to
      the human hematological syndrome paroxysmal nocturnal hemoglobinuria, the
      relevance of DAF in autoimmune tissue damage such as immune glomerulonephritis
      remains to be determined. In this study, we have investigated the susceptibility
      of knockout mice that are deficient in GPI-anchored DAF to nephrotoxic serum
      nephritis. Injection of a subnephritogenic dose of rabbit anti-mouse glomerular
      basement membrane serum induced glomerular disease in DAF knockout mice but not
      in wild-type controls. When examined at 8 days after anti-glomerular basement
      membrane treatment, DAF knockout mice had a much higher percentage of diseased
      glomeruli than wild-type mice (68.8 +/- 25.0 vs 10.0 +/- 3.5%; p < 0.01).
      Morphologically, DAF knockout mice displayed increased glomerular volume (516 +/-
      68 vs 325 +/- 18 x 10(3) microm(3) per glomerulus; p < 0.0001) and cellularity
      (47.1 +/- 8.9 vs 32.0 +/- 3.1 cells per glomerulus; p < 0.01). Although the blood
      urea nitrogen level showed no difference between the two groups, proteinuria was
      observed in the knockout mice but not in the wild-type mice (1.4 +/- 0.7 vs 0.02
      +/- 0.01 mg/24 h albumin excretion). The morphological and functional
      abnormalities in the knockout mouse kidney were associated with evidence of
      increased complement activation in the glomeruli. These results support the
      conclusion that membrane C3 convertase inhibitors like DAF play a protective role
      in complement-mediated immune glomerular damage in vivo.

PMID- 11509625
TI  - Murine cytomegalovirus infection alters Th1/Th2 cytokine expression, decreases
      airway eosinophilia, and enhances mucus production in allergic airway disease.
AB  - Concomitant infection of murine CMV (MCMV), an opportunistic respiratory
      pathogen, altered Th1/Th2 cytokine expression, decreased bronchoalveolar lavage
      (BAL) fluid eosinophilia, and increased mucus production in a murine model of OVA
      induced allergic airway disease. Although no change in the total number of
      leukocytes infiltrating the lung was observed between challenged and
      MCMV/challenged mice, the cellular profile differed dramatically. After 10 days
      of OVA-aerosol challenge, eosinophils comprised 64% of the total leukocyte
      population in BAL fluid from challenged mice compared with 11% in MCMV/challenged
      mice. Lymphocytes increased from 11% in challenged mice to 30% in MCMV/challenged
      mice, and this increase corresponded with an increase in the ratio of CD8(+) to
      CD4(+)TCRalphabeta lymphocytes. The decline in BAL fluid eosinophilia was
      associated with a change in local Th1/Th2 cytokine profiles. Enhanced levels of
      IL-4, IL-5, IL-10, and IL-13 were detected in lung tissue from challenged mice by
      RNase protection assays. In contrast, MCMV/challenged mice transiently expressed
      elevated levels of IFN-gamma and IL-10 mRNAs, as well as decreased levels of IL
      4, IL-5, and IL-13 mRNAs. Elevated levels of IFN-gamma and reduced levels of IL-5
      were also demonstrated in BAL fluid from MCMV/challenged mice. Histological
      evaluation of lung sections revealed extensive mucus plugging and epithelial cell
      hypertrophy/hyperplasia only in MCMV/challenged mice. Interestingly, the
      development of airway hyperresponsiveness was observed in challenged mice, not
      MCMV/challenged mice. Thus, MCMV infection can modulate allergic airway
      inflammation, and these findings suggest that enhanced mucus production may occur
      independently of BAL fluid eosinophilia.

PMID- 11509626
TI  - Eotaxin represents the principal eosinophil chemoattractant in a novel murine
      asthma model induced by house dust containing cockroach allergens.
AB  - Asthma represents a serious health problem particularly for inner city children,
      and recent studies have identified that cockroach allergens trigger many of these
      asthmatic attacks. This study tested the concept that asthma-like pulmonary
      inflammation may be induced by house dust containing cockroach allergens. An
      aqueous extract was prepared from a house dust sample containing endotoxin and
      high levels of cockroach allergens. BALB/c mice were immunized with the house
      dust extract (HDE) and received two additional pulmonary challenges.
      Bronchoalveolar lavage (BAL) eosinophil counts and eotaxin levels were
      significantly increased in immunized mice exposed to the HDE, whereas neutrophils
      were the predominant BAL inflammatory cell in the unimmunized mice. Kinetics
      studies in immunized mice demonstrated a peak pulmonary inflammatory response 48
      h after the last challenge. The allergic response in this model was further
      confirmed by histological and physiological studies demonstrating a significant
      influx of eosinophils and lymphocytes in the peribronchial area, and severe
      airway hyperreactivity through whole-body plethysmography. The specificity of the
      response was established by immunizing with HDE and challenging with purified
      cockroach allergen, which induced pulmonary eosinophilia and airway
      hyperreactivity. Ab inhibition of eotaxin significantly inhibited the number of
      BAL eosinophils. These data describe a novel murine model of asthma-like
      pulmonary inflammation induced by house dust containing endotoxin and cockroach
      allergens and further demonstrate that eotaxin represents the principal
      chemoattractant for the recruitment of the pulmonary eosinophils.

PMID- 11509627
TI  - IL-8 released constitutively by primary bronchial epithelial cells in culture
      forms an inactive complex with secretory component.
AB  - The bronchial epithelium is a source of both alpha and beta chemokines and,
      uniquely, of secretory component (SC), the extracellular ligand-binding domain of
      the polymeric IgA receptor. Ig superfamily relatives of SC, such as IgG and
      alpha(2)-macroglobulin, bind IL-8. Therefore, we tested the hypothesis that SC
      binds IL-8, modifying its activity as a neutrophil chemoattractant. Primary
      bronchial epithelial cells were cultured under conditions to optimize SC
      synthesis. The chemokines IL-8, epithelial neutrophil-activating peptide-78,
      growth-related oncogene alpha, and RANTES were released constitutively by
      epithelial cells from both normal and asthmatic donors and detected in high m.w.
      complexes with SC. There were no qualitative differences in the production of SC
      chemokine complexes by epithelial cells from normal or asthmatic donors, and in
      all cases this was the only form of chemokine detected. SC contains 15% N-linked
      carbohydrate, and complete deglycosylation with peptide N-glycosidase F abolished
      IL-8 binding. In micro-Boyden chamber assays, no IL-8-dependent neutrophil
      chemotactic responses to epithelial culture supernatants could be demonstrated.
      SC dose-dependently (IC(50) approximately 0.3 nM) inhibited the neutrophil
      chemotactic response to rIL-8 (10 nM) in micro-Boyden chamber assays and also
      inhibited IL-8-mediated neutrophil transendothelial migration. SC inhibited the
      binding of IL-8 to nonspecific binding sites on polycarbonate filters and
      endothelial cell monolayers, and therefore the formation of haptotactic
      gradients, without effects on IL-8 binding to specific receptors on neutrophils.
      The data indicate that in the airways IL-8 may be solubilized and inactivated by
      binding to SC.

PMID- 11509628
TI  - The affinity of integrin alpha(4)beta(1) governs lymphocyte migration.
AB  - The interaction of integrin alpha(4)beta(1) with endothelial VCAM-1 controls the
      trafficking of lymphocytes from blood into peripheral tissues. Cells actively
      regulate the affinity of alpha(4)beta(1) for VCAM-1 (activation). To investigate
      the biological function of alpha(4)beta(1) activation, we isolated Jurkat T cell
      lines with defective alpha(4)beta(1) activation. Using these cells, we found that
      alpha(4)beta(1)-stimulated alpha(L)beta(2)-dependent cell migration was
      dramatically reduced in cells with defects in alpha(4)beta(1) activation. These
      cells required 20 times more VCAM-1 to promote alpha(L)beta(2)-dependent cell
      migration. This defect was at the level of alpha(4)beta(1) affinity as an
      activating alpha(4)beta(1) Ab rescued alpha(4)beta(1)-stimulated alpha(L)beta(2)
      dependent migration. In contrast, migration of alpha(4)beta(1) activation
      defective cells on VCAM-1 alone was enhanced at higher VCAM-1 densities. Thus,
      alpha(4)beta(1) activation determines a set point or threshold at which VCAM-1
      can regulate alpha(L)beta(2)-dependent as well as alpha(4)beta(1)-dependent cell
      migration. Changes in this set point may specify preferred anatomical sites of
      integrin-dependent leukocyte emigration from the bloodstream.

PMID- 11509629
TI  - Roles of cyclooxygenase (COX)-1 and COX-2 in prostanoid production by human
      endothelial cells: selective up-regulation of prostacyclin synthesis by COX-2.
AB  - The two cyclooxygenase (COX) isoforms, COX-1 and COX-2, both metabolize
      arachidonic acid to PGH(2), the common substrate for thromboxane A(2) (TXA(2)),
      prostacyclin (PGI(2)), and PGE(2) synthesis. We characterized the synthesis of
      these prostanoids in HUVECs in relation to COX-1 and COX-2 activity. Untreated
      HUVEC expressed only COX-1, whereas addition of IL-1beta caused induction of COX
      2. TXA(2) was the predominant COX-1-derived product, and TXA(2) synthesis changed
      little with up-regulation of COX-2 by IL-1beta (2-fold increase). By contrast,
      COX-2 up-regulation was associated with large increases in the synthesis of
      PGI(2) and PGE(2) (54- and 84-fold increases, respectively). Addition of the
      selective COX-2 inhibitor, NS-398, almost completely abolished PGI(2) and PGE(2)
      synthesis, but had little effect on TXA(2) synthesis. The up-regulation of COX-2
      by IL-1beta was accompanied by specific up-regulation of PGI synthase and PGE
      synthase, but not TX synthase. An examination of the substrate concentration
      dependencies showed that the pathway of TXA(2) synthesis was saturated at a 20
      fold lower arachidonic acid concentration than that for PGI(2) and PGE(2)
      synthesis. In conclusion, endothelial prostanoid synthesis appears to be
      differentially regulated by the induction of COX-2. The apparent PGI(2) and
      PGE(2) linkage with COX-2 activity may be explained by a temporal increase in
      total COX activity, together with selective up-regulation of PGI synthase and PGE
      synthase, and different kinetic characteristics of the terminal synthases. These
      findings have particular importance with regard to the potential for
      cardiovascular consequences of COX-2 inhibition.

PMID- 11509630
TI  - CD18 dependency of transendothelial neutrophil migration differs during acute
      pulmonary inflammation.
AB  - Neutrophil extravasation during inflammation can occur either by a mechanism that
      requires the neutrophil integrin complex, CD18, or by an alternative CD18
      independent route. Which of the two pathways is used has been shown to depend on
      the site and nature of the inflammatory insult. More recent evidence suggests
      that selection may also depend on whether inflammation is chronic or acute, but
      why this is the case remains unknown. Using an in vitro model that supports both
      migratory mechanisms, we examined the CD18 dependency of migration of neutrophils
      isolated from patients with either chronic or acute pulmonary infection. Chronic
      neutrophils were found to behave like normal neutrophils by migrating to IL-8 and
      leukotriene B(4) using the CD18-independent pathway, but to the bacterial
      product, FMLP, using the CD18-dependent route. In contrast, migration of acute
      neutrophils to all of these stimuli was CD18 dependent. Normal neutrophils could
      be manipulated to resemble acute neutrophils by exposing them to FMLP before
      migration, which resulted in a "switch" from the CD18-independent to -dependent
      mechanism during migration to IL-8 or leukotriene B(4). Although treatment of
      normal neutrophils with FMLP caused selective down-regulation of the IL-8
      receptor, CXCR2, and acute neutrophils were found to have less CXCR2 than normal,
      a functional relationship between decreased CXCR2 and selection of CD18-dependent
      migration was not demonstrated. Results indicate that selection of the CD18
      dependent or -independent migration mechanism can be controlled by the neutrophil
      and suggest that the altered CD18 requirements of acute neutrophils may be due to
      priming in the circulation during acute infection.

PMID- 11509631
TI  - A novel function of phosphorothioate oligodeoxynucleotides as chemoattractants
      for primary macrophages.
AB  - Phosphorothioate cytosine-guanine oligodeoxynucleotides (CpG PS-ODNs) has been
      reported to induce Th1 immune responses against coadministered Ags more
      efficiently than phosphodiester CpG ODNs (CpG PO-ODNs). Here, we demonstrated
      that PS-ODNs, but not PO-ODNs, have a chemotactic effect on primary macrophages,
      which is independent of the CpG motif. In addition, the conjugation of a
      hexameric dG run (dG(6) run) at the 3' terminus reduced the concentration
      required for the optimal chemotactic activity of PS-ODNs by approximately 10
      fold. Endosomal maturation blockers, such as monensin and chloroquine, inhibited
      the chemotactic effect of PS-ODNs. The inhibition of the activities of p38
      mitogen-activated protein (MAP) kinase, and extracellular signal-related kinases
      (ERKs) as well as phosphoinositide 3-kinase with their specific inhibitors also
      resulted in suppressing the chemotaxis of primary macrophages induced by PS-ODNs.
      These results indicate that the PS-ODN-mediated chemotaxis requires the
      activation of ERKs, p38 MAP kinase, and phosphoinositide 3-kinase as well as
      endosomal maturation. In addition, the phosphorylations of the p38 MAP kinase,
      ERKs, and protein kinase B, Akt, were induced by PS-ODN, which were further
      enhanced by the presence of both a dG(6) run and CpG motifs. Our findings suggest
      that the chemotactic activity of PS-ODNs may be one of the mechanisms by which PS
      ODNs exhibit stronger immunomodulatory activities than PO-ODNs in vivo.

PMID- 11509632
TI  - IL-13 and IL-4 up-regulate cysteinyl leukotriene 1 receptor expression in human
      monocytes and macrophages.
AB  - The cysteinyl (Cys) leukotrienes (LT)C(4), LTD(4), and LTE(4), are lipid
      mediators that have been implicated in the pathogenesis of asthma. The human
      LTD(4) receptor (CysLT(1)R) was recently cloned and characterized. The present
      work was undertaken to study the potential modulation of CysLT(1)R expression by
      the Th2 cytokines IL-13 and IL-4. In this study, we report that IL-13 up
      regulates CysLT(1)R mRNA levels, with consequently enhanced CysLT(1)R protein
      expression and function in human monocytes and monocyte-derived macrophages.
      CysLT(1)R mRNA expression was augmented 2- to 5-fold following treatment with IL
      13 and was due to enhanced transcriptional activity. The effect was observed
      after 4 h, was maximal by 8 h, and maintained at 24 h. IL-4, but not IFN-gamma,
      induced a similar pattern of CysLT(1)R up-regulation. Monocytes pretreated with
      IL-13 or IL-4 for 24 h showed enhanced CysLT(1)R protein expression, as assessed
      by flow cytometry using a polyclonal anti-CysLT(1)R Ab. They also showed enhanced
      responsiveness to LTD(4), but not to LTB(4), in terms of Ca(2+) mobilization, as
      well as augmented chemotactic activity. Our findings suggest a possible mechanism
      by which IL-13 and IL-4 can modulate CysLT(1)R expression on monocytes and
      macrophages, and consequently their responsiveness to LTD(4), and thus contribute
      to the pathogenesis of asthma and allergic diseases.

PMID- 11509633
TI  - Human IgA activates the complement system via the mannan-binding lectin pathway.
AB  - The recently identified lectin pathway of the complement system, initiated by
      binding of mannan-binding lectin (MBL) to its ligands, is a key component of
      innate immunity. MBL-deficient individuals show an increased susceptibility for
      infections, especially of the mucosal system. We examined whether IgA, an
      important mediator of mucosal immunity, activates the complement system via the
      lectin pathway. Our results indicate a dose-dependent binding of MBL to
      polymeric, but not monomeric IgA coated in microtiter plates. This interaction
      involves the carbohydrate recognition domain of MBL, because it was calcium
      dependent and inhibited by mannose and by mAb against this domain of MBL. Binding
      of MBL to IgA induces complement activation, as demonstrated by a dose-dependent
      deposition of C4 and C3 upon addition of a complement source. The MBL
      concentrations required for IgA-induced C4 and C3 activation are well below the
      normal MBL plasma concentrations. In line with these experiments, serum from
      individuals having mutations in the MBL gene showed significantly less activation
      of C4 by IgA and mannan than serum from wild-type individuals. We conclude that
      MBL binding to IgA results in complement activation, which is proposed to lead to
      a synergistic action of MBL and IgA in antimicrobial defense. Furthermore, our
      results may explain glomerular complement deposition in IgA nephropathy.

PMID- 11509634
TI  - Fibrinogen induces IL-8 synthesis in human neutrophils stimulated with formyl
      methionyl-leucyl-phenylalanine or leukotriene B(4).
AB  - Human exudative neutrophils have greatly increased stores of the neutrophil
      chemoattractant IL-8 compared with peripheral blood cells, but the mechanism for
      the increase is not defined. In this report, we show that treatment of peripheral
      blood neutrophils with the chemotactic peptide fMLP or with leukotriene B(4) or
      fibrinogen results in little increase in the production of IL-8 by peripheral
      blood neutrophils. However, a chemotactically active dose of fMLP (5 x 10(-9) M)
      or leukotriene B(4) (1 x 10(-7) M) in the presence of a physiological
      concentration (2 mg/ml) of fibrinogen results in a receptor-mediated, pertussis
      toxin-sensitive, synergistic 30-fold increase in IL-8 synthesis. The levels of IL
      8 attained are comparable to those observed in exudative cells. Higher
      concentrations of fMLP (1 x 10(-7) M) are associated with reduced IL-8 protein
      synthesis without IL-8 degradation, indicating a sensitive regulatory mechanism
      for IL-8 production. Treatment of neutrophils with fibrinogen and fMLP resulted
      in minimal changes in the steady state levels of mRNA for macrophage inflammatory
      protein-1alpha and -1beta and monocyte chemoattractant protein-1. In contrast, in
      the presence of fibrinogen, the steady-state level of neutrophil IL-8 mRNA
      increased 8-fold with 5 x 10(-9) M fMLP but was not decreased with 1 x 10(-7) M
      fMLP, suggesting that neutrophils are specifically adapted to modulate neutrophil
      IL-8 synthesis through transcriptional and posttranscriptional mechanisms. The
      data indicate that fibrinogen can function not only as a substrate in the
      clotting cascade, but also as an important effector during the evolution of the
      innate immune response.

PMID- 11509635
TI  - A role for IL-18 in neutrophil activation.
AB  - IL-18 expression and functional activity has been identified in several
      autoimmune and infectious diseases. To clarify the potential role of IL-18 during
      early innate immune responses, we have explored the capacity of IL-18 to activate
      neutrophils. Human peripheral blood-derived neutrophils constitutively expressed
      IL-18R (alpha and beta) commensurate with the capacity to rapidly respond to IL
      18. IL-18 induced cytokine and chemokine release from neutrophils that was
      protein synthesis dependent, up-regulated CD11b expression, induced granule
      release, and enhanced the respiratory burst following exposure to fMLP, but had
      no effect upon the rate of neutrophil apoptosis. The capacity to release cytokine
      and chemokine was significantly enhanced in neutrophils derived from rheumatoid
      arthritis synovial fluid, indicating differential responsiveness to IL-18
      dependent upon prior neutrophil activation in vivo. Finally, IL-18 administration
      promoted neutrophil accumulation in vivo, whereas IL-18 neutralization suppressed
      the severity of footpad inflammation following carrageenan injection. The latter
      was accompanied by reduction in tissue myeloperoxidase expression and suppressed
      local TNF-alpha production. Together, these data define a novel role for IL-18 in
      activating neutrophils and thereby promoting early innate immune responses.

PMID- 11509636
TI  - Fibrinogen stimulates macrophage chemokine secretion through toll-like receptor
      4.
AB  - Extravascular fibrin deposition is an early and persistent hallmark of
      inflammatory responses. Fibrin is generated from plasma-derived fibrinogen, which
      escapes the vasculature in response to endothelial cell retraction at sites of
      inflammation. Our ongoing efforts to define the physiologic functions of
      extravasated fibrin(ogen) have led to the discovery, reported here, that
      fibrinogen stimulates macrophage chemokine secretion. Differential mRNA
      expression analysis and RNase protection assays revealed that macrophage
      inflammatory protein-1alpha (MIP-1alpha), MIP-1beta, MIP-2, and monocyte
      chemoattractant protein-1 are fibrinogen inducible in the RAW264.7 mouse
      macrophage-like cell line, and ELISA confirmed that both RAW264.7 cells and
      primary murine thioglycolate-elicited peritoneal macrophages up-regulate the
      secretion of monocyte chemoattractant protein-1 >100-fold upon exposure to
      fibrinogen. Human U937 and THP-1 precursor-1 (THP-1) monocytic cell lines also
      secreted chemokines in response to fibrinogen, upon activation with IFN-gamma and
      differentiation with vitamin D(3), respectively. LPS contamination could not
      account for our observations, as fibrinogen-induced chemokine secretion was
      sensitive to heat denaturation and was unaffected by the pharmacologic LPS
      antagonist polymyxin B. Nevertheless, fibrinogen- and LPS-induced chemokine
      secretion both apparently required expression of functional Toll-like receptor 4,
      as each was diminished in macrophages derived from C3H/HeJ mice. Thus, innate
      responses to fibrinogen and bacterial endotoxin may converge at the
      evolutionarily conserved Toll-like recognition molecules. Our data suggest that
      extravascular fibrin(ogen) induces macrophage chemokine expression, thereby
      promoting immune surveillance at sites of inflammation.

PMID- 11509637
TI  - Differential role of CD18 integrins in mediating lung neutrophil sequestration
      and increased microvascular permeability induced by Escherichia coli in mice.
AB  - The in vivo contributions of CD18 integrin-dependent and -independent mechanisms
      in mediating the increases in lung neutrophil (polymorphonuclear leukocyte; PMN)
      sequestration and microvascular permeability are not well understood. We
      determined the time course of these responses to Gram-negative sepsis in the
      mouse lung and addressed the specific contributions of CD18 integrins and ICAM-1.
      PMN sequestration in the lung was assessed by morphometric analysis, and
      transalveolar PMN migration was assessed by bronchoalveolar lavage. Lung tissue
      PMN number increased by 6-fold within 1 h after i.p. Escherichia coli challenge;
      this value peaked at 3 h (7-fold above control) and decreased at 12 h (3.5-fold
      above control). PMN migration into the airspace was delayed; the value peaked at
      6 h and remained elevated up to 12 h. Saturating concentrations of anti-CD18 and
      anti-ICAM-1 mAbs reduced lung tissue PMN sequestration and migration; however,
      peak responses at 3 and 6 h were inhibited by 40%, indicating that only a small
      component of PMN sequestration and migration was CD18 dependent at these times.
      In contrast to the time-dependent decreased role of CD18 integrins in mediating
      PMN sequestration and migration, CD18 and ICAM-1 blockade prevented the increase
      in lung microvascular permeability and edema formation at all times after E. coli
      challenge. Thus, Gram-negative sepsis engages CD18/ICAM-1-independent mechanisms
      capable of the time-dependent amplification of lung PMN sequestration and
      migration. The increased pulmonary microvascular permeability induced by E. coli
      is solely the result of engagement of CD18 integrins even when PMN accumulation
      and migration responses are significantly CD18 independent.

PMID- 11509638
TI  - Bystander activation involving T lymphocytes in herpetic stromal keratitis.
AB  - Herpes simplex virus infection of mouse corneas can lead to the development of an
      immunopathological lesion, termed herpetic stromal keratitis (HSK). Such lesions
      also occur in TCR-transgenic mice backcrossed to SCID (TgSCID) that are unable to
      mount detectable HSV-specific immune responses. The present study demonstrates
      that lesion expression in such mice depends on continuous viral replication,
      whereas in immunocompetent mice, lesions occurred even if virus replication was
      terminated at 4 days after infection. The continuous replication in TgSCID mice
      was considered necessary to produce an activating stimulus to CD4(+) T cells that
      invade the cornea. Lesions in TgSCID were resistant to control by cyclosporin A,
      but were inhibited by treatment with rapamycin. This result was interpreted to
      indicate that T cell activation involved a non-TCR-mediated cytokine-driven
      bystander mechanism. Bystander activation was also shown to play a role in HSK
      lesions in immunocompetent mice. Accordingly, in immunocompetent DO11.10 mice,
      lesions were dominated by KJ1.26(+) OVA-specific CD4(+) T cells that were
      unreactive with HSV. In addition, KJ1.26(+) HSV nonimmune cells parked in
      ocularly infected BALB/c mice were demonstrable in HSK lesions. These results
      provide insight for the choice of new strategies to manage HSK, an important
      cause of human blindness.

PMID- 11509640
TI  - Lactoferrin binds CpG-containing oligonucleotides and inhibits their
      immunostimulatory effects on human B cells.
AB  - Unmethylated CpG dinucleotide motifs in bacterial DNA, as well as
      oligodeoxynucleotides (ODN) containing these motifs, are potent stimuli for many
      host immunological responses. These CpG motifs may enhance host responses to
      bacterial infection and are being examined as immune activators for therapeutic
      applications in cancer, allergy/asthma, and infectious diseases. However, little
      attention has been given to processes that down-modulate this response. The iron
      binding protein lactoferrin is present at mucosal surfaces and at sites of
      infection. Since lactoferrin is known to bind DNA, we tested the hypothesis that
      lactoferrin will bind CpG-containing ODN and modulate their biological activity.
      Physiological concentrations of lactoferrin (regardless of iron content) rapidly
      bound CpG ODN. The related iron-binding protein transferrin lacked this capacity.
      ODN binding by lactoferrin did not require the presence of CpG motifs and was
      calcium independent. The process was inhibited by high salt, and the highly
      cationic N-terminal sequence of lactoferrin (lactoferricin B) was equivalent to
      lactoferrin in its ODN-binding ability, suggesting that ODN binding by
      lactoferrin occurs via charge-charge interaction. Heparin and bacterial LPS,
      known to bind to the lactoferricin component of lactoferrin, also inhibited ODN
      binding. Lactoferrin and lactoferricin B, but not transferrin, inhibited CpG ODN
      stimulation of CD86 expression in the human Ramos B cell line and decreased
      cellular uptake of ODN, a process required for CpG bioactivity. Lactoferrin
      binding of CpG-containing ODN may serve to modulate and terminate host response
      to these potent immunostimulatory molecules at mucosal surfaces and sites of
      bacterial infection.

PMID- 11509639
TI  - Methotrexate suppresses NF-kappaB activation through inhibition of IkappaBalpha
      phosphorylation and degradation.
AB  - Methotrexate (MTX), a folate antagonist, is a commonly used anti-inflammatory,
      antiproliferative, and immunosuppressive drug whose mode of action is not fully
      established. Due to the central role of NF-kappaB in these responses, we
      postulated that MTX must mediate its effects through suppression of NF-kappaB
      activation. We investigated the effects of MTX on NF-kappaB activation induced by
      TNF in Jurkat cells. The treatment of these cells with MTX suppressed TNF-induced
      NF-kappaB activation with optimum effects occurring at 10 microM MTX for 60 min.
      These effects were not restricted to Jurkat cells because other cell types were
      also inhibited. Besides TNF, MTX also suppressed the NF-kappaB activation induced
      by various other inflammatory stimuli. The suppression of TNF-induced NF-kappaB
      activation by MTX correlated with inhibition of IkappaBalpha degradation,
      suppression of IkappaBalpha phosphorylation, abrogation of IkappaBalpha kinase
      activation, and inhibition of NF-kappaB-dependent reporter gene expression.
      Because ecto 5' nucleotidase inhibitor (alpha,beta-methylene adenosine-5'
      diphosphate) blocked the effect of MTX, adenosine mimicked the effect of MTX, and
      adenosine A2b receptor antagonist (3,7-dimethyl-1-propargylxanthine) reversed the
      inhibitory effect of MTX, we suggest that MTX suppresses NF-kappaB activation by
      releasing adenosine. A partial reversal of MTX-induced NF-kappaB suppression by
      thymidine and folinic acid indicates the role of the thymidylate synthase pathway
      also. Overall, our results clearly demonstrate that MTX suppresses NF-kappaB
      activation through the release of adenosine, which may contribute to the role of
      MTX in anti-inflammatory, immunomodulatory, and antiproliferative effects.

PMID- 11509641
TI  - Enhanced dendritic cell-driven proliferation and anti-HIV activity of CD8(+) T
      cells by a new phenothiazine derivative, aminoperazine.
AB  - T cell anergy, apoptosis, and chronic activation of T lymphocytes are prevailing
      features of HIV infection. The inability to develop an efficient natural
      antiviral activity in infected patients might be the consequence of a failure of
      the Ag presentation by dendritic cells (DCs) in chronically activated lymphoid
      tissues. We have identified a new phenothiazine derivative aminoperazine (APR; 2
      amino-10-[3'-(1-methyl-4-piperazinyl)propyl]phenothiazine, C(20)H(26)N(4)S; m.w.
      354.51) able to increase (effective dose from 0.1 to 100 nM) the Ag-specific DC
      driven proliferation and differentiation of in vitro HIV-infected and uninfected
      normal donor T cells and of T cells from HIV-1-infected patients. The
      immunomodulatory effect of APR-sensitized DCs were ascribed to soluble factors
      derived from DCs. APR was also capable of increasing HIV gag-p24-specific
      proliferation and anti-HIV cytotoxic activity of patients' CD8(+) T cells against
      autologous B-lymphoblastoid cell lines expressing a HIV gag gene, resulting in
      the suppression of both proviral DNA and supernatant viral RNA in the HIV-1
      infected patients' T cell culture. This new phenothiazine derivative (APR) might
      be used for boosting the immune response of vaccinated individuals and for
      restoring the immunity of immunocompromised patients.

PMID- 11509642
TI  - Accumulation and activation-induced release of preformed Fas (CD95) ligand during
      the pathogenesis of experimental graft-versus-host disease.
AB  - Fas (CD95/APO-1) ligand (FasL)-mediated cytotoxicity has been implicated in
      tissue destruction in a variety of diseases, including acute graft-vs-host
      disease (GVHD). In this study, we have analyzed FasL expression and regulation
      during the course of experimental murine acute GVHD. Although activation-induced
      FasL-mediated cytotoxicity in control T cells was sensitive to the
      immunosuppressant cyclosporin A, we observed that functional FasL expression of
      GVHD T cells became increasingly cyclosporin A unresponsive. This was found to be
      the result of a massive in vivo accumulation and intracellular storage of FasL
      protein and its release in a transcription- and protein synthesis-independent
      manner. Immunohistochemistry analysis of FasL expression in situ revealed
      accumulation of FasL-expressing cells in the spleen, the liver, and small
      intestine, with a typical cytoplasmic and granular expression pattern. Thus, we
      conclude that the release of preformed FasL by infiltrating donor T cells may
      contribute to recipient tissue damage during the pathogenesis of acute GVHD.

PMID- 11509643
TI  - Prevention of experimental autoimmune encephalomyelitis in the common marmoset
      (Callithrix jacchus) using a chimeric antagonist monoclonal antibody against
      human CD40 is associated with altered B cell responses.
AB  - Inhibition of CD40-CD40 ligand interaction is a potentially effective approach
      for treatment of autoimmune diseases, such as multiple sclerosis. We have
      investigated this concept with a chimeric antagonist anti-human CD40 mAb (ch5D12)
      in the marmoset monkey experimental autoimmune encephalomyelitis (EAE) model.
      Marmosets were immunized with recombinant human myelin oligodendrocyte
      glycoprotein (rMOG) and treated from the day before immunization (day -1) until
      day 50 with either ch5D12 (5 mg/kg every 2-4 days) or placebo. On day 41 after
      the induction of EAE, four of four placebo-treated monkeys had developed severe
      clinical EAE, whereas all animals from the ch5D12-treated group were completely
      free of disease symptoms. High serum levels of ch5D12 associated with complete
      coating of CD40 on circulating B cells were found. At necropsy placebo- and
      ch5D12-treated animals showed similar MOG-specific lymphoproliferative responses
      in vitro, but ch5D12 treatment resulted in strongly reduced anti-MOG IgM Ab
      responses and delayed anti-MOG IgG responses. Most importantly, treatment with
      ch5D12 prevented intramolecular spreading of epitope recognition. Postmortem
      magnetic resonance imaging and immunohistologic analysis of the CNS showed a
      markedly reduced lesion load after ch5D12 treatment. In conclusion, the strong
      reduction of clinical, pathological, and radiological aspects of EAE by ch5D12
      treatment in this preclinical model points to a therapeutic potential of this
      engineered antagonist anti-CD40 mAb for multiple sclerosis.

PMID- 11509644
TI  - Plasmid vaccination with insulin B chain prevents autoimmune diabetes in nonobese
      diabetic mice.
AB  - The insulin B (InsB) chain bears major type 1 diabetes-associated epitopes of
      significance for disease in humans and nonobese diabetic (NOD) mice. Somatic
      expression of InsB chain initiated early in life by plasmid inoculation resulted
      in substantial protection of female NOD mice against disease. This was associated
      with a T2 shift in spleen, expansion of IL-4-producing and, to a lesser extent,
      of IFN-gamma-secreting T cells in pancreatic lymph nodes, as well as
      intermolecular Th2 epitope spreading to glutamic acid decarboxylase determinants.
      A critical role of IL-4 for the Ag-specific protective effect triggered by
      plasmid administration was revealed in female IL-4(-/-) NOD mice that developed
      diabetes and higher Th1 responses. Coadministration of IL-4-expressing plasmid or
      extension of the vaccination schedule corrected the unfavorable response of male
      NOD mice to DNA vaccination with InsB chain. Thus, plasmid-mediated expression of
      the InsB chain early in diabetes-prone mice has the potential to prevent
      transition to full-blown disease depending on the presence of IL-4.

PMID- 11509645
TI  - Immunoreactivity of organic mimeotopes of the E2 component of pyruvate
      dehydrogenase: connecting xenobiotics with primary biliary cirrhosis.
AB  - In primary biliary cirrhosis (PBC), the major autoepitope recognized by both T
      and B cells is the inner lipoyl domain of the E2 component of pyruvate
      dehydrogenase. To address the hypothesis that PBC is induced by xenobiotic
      exposure, we took advantage of ab initio quantum chemistry and synthesized the
      inner lipoyl domain of E2 component of pyruvate dehydrogenase, replacing the
      lipoic acid moiety with synthetic structures designed to mimic a xenobiotically
      modified lipoyl hapten, and we quantitated the reactivity of these structures
      with sera from PBC patients. Interestingly, antimitochondrial Abs from all
      seropositive patients with PBC, but no controls, reacted against 3 of the 18
      organic modified autoepitopes significantly better than to the native domain. By
      structural analysis, the features that correlated with autoantibody binding
      included synthetic domain peptides with a halide or methyl halide in the meta or
      para position containing no strong hydrogen bond accepting groups on the phenyl
      ring of the lysine substituents, and synthetic domain peptides with a relatively
      low rotation barrier about the linkage bond. Many chemicals including
      pharmaceuticals and household detergents have the potential to form such
      halogenated derivatives as metabolites. These data reflect the first time that an
      organic compound has been shown to serve as a mimeotope for an autoantigen and
      further provide evidence for a potential mechanism by which environmental organic
      compounds may cause PBC.

PMID- 11509646
TI  - Absence of macrophage-inflammatory protein-1alpha delays central nervous system
      demyelination in the presence of an intact blood-brain barrier.
AB  - Chemokines are small chemotactic cytokines that modulate leukocyte recruitment
      and activation during inflammation. Here, we describe the role of macrophage
      inflammatory protein-1alpha (MIP-1alpha) during cuprizone intoxication, a model
      where demyelination of the CNS features a large accumulation of
      microglia/macrophage without T cell involvement or blood-brain barrier
      disruption. RNase protection assays showed that mRNA for numerous chemokines were
      up-regulated during cuprizone treatment in wild-type, C57BL/6 mice. RANTES,
      inflammatory protein-10, and monocyte chemoattractant protein-1 showed greatest
      expression with initiation of insult at 1-2 wk of treatment, whereas MIP-1alpha
      and beta increased later at 4-5 wk, coincident with peak demyelination and
      cellular accumulation. The function of MIP-1alpha during demyelination was tested
      in vivo by exposing MIP-1alpha knockout mice (MIP-1alpha(-/-)) to cuprizone and
      comparing pathology to wild-type mice. Demyelination at 3.5 wk of treatment was
      significantly decreased in MIP-1alpha(-/-) mice ( approximately 36% reduction), a
      result confirmed by morphology at the electron microscopic level. The delay in
      demyelination was correlated to apparent decreases in microglia/macrophage and
      astrocyte accumulation and in TNF-alpha protein levels. It was possible that
      larger effects of the MIP-1alpha deficiency were being masked by other redundant
      chemokines. Indeed, RNase protection assays revealed increased expression of
      several chemokine transcripts in both untreated and cuprizone-treated MIP-1alpha(
      /-) mice. Nonetheless, despite this possible compensation, our studies show the
      importance of MIP-1alpha in demyelination in the CNS and highlight its effect,
      particularly on cellular recruitment and cytokine regulation.

PMID- 11509647
TI  - Predominant Th2/Tc2 polarity of tumor-infiltrating lymphocytes in human cervical
      cancer.
AB  - Cytotoxic T lymphocytes (Tc) play a central role in cellular immunity against
      cancers. The cytotoxic potential of freshly isolated tumor-infiltrating
      lymphocytes (TILs) is usually not expressed. This suggests the possible existence
      of as yet unspecified and perhaps complex immunosuppressive factors or cytokines
      that affect the anti-tumor capacity of these TILs in the tumor milieu. In the
      present study, we demonstrated for the first time that TILs derived from human
      cervical cancer tissue consist mainly of Th2/Tc2 phenotypes. In vitro kinetic
      assays further revealed that cancer cells could direct the tumor-encountered T
      cells toward the Th2/Tc2 polarity. Cancer cells promote the production of IL-4
      and down-regulate the production of IFN-gamma in cancer-encountered T cells. The
      regulatory effects of cervical cancer cells are mediated mainly by IL-10, and TGF
      beta plays only a synergistic role. The cancer-derived effects can be reversed by
      neutralizing anti-IL-10 and anti-TGF-beta Abs. IL-10 and TGF-beta are present in
      cancer tissue and weakly expressed in precancerous tissue, but not in normal
      cervical epithelial cells. Our study strongly suggests important regulatory roles
      of IL-10 and TGF-beta in cancer-mediated immunosuppression.

PMID- 11509648
TI  - Early chemokine cascades in murine cardiac grafts regulate T cell recruitment and
      progression of acute allograft rejection.
AB  - The identification of early inflammatory events after transplant in solid tissue
      organ grafts that may direct T cell recruitment and promote acute allograft
      rejection remain largely unknown. To better understand temporal aspects of early
      inflammatory events in vascularized organ grafts, we tested the intragraft
      expression of four different chemokines in heterotopically transplanted A/J (H
      2(a)) and syngeneic heart grafts in C57BL/6 (H-2(b)) recipient mice from 1.5 to
      48 h after transplant. Similar temporal expression patterns and equivalent levels
      of chemokine expression were observed in both syngeneic and allogeneic cardiac
      allografts during this time period. Expression of the neutrophil chemoattractant
      growth-related oncogene alpha (KC) was observed first and reached peak levels by
      6 h after transplant and was followed by the monocyte/macrophage chemoattractant
      protein-1 (JE) and then macrophage inflammatory proteins 1beta and 1alpha.
      Administration of rabbit KC antiserum to allograft recipients within 30 min of
      cardiac transplantation attenuated downstream events including intra-allograft
      expression of the T cell chemoattractants IFN-gamma-inducible protein-10 and
      monokine induced by IFN-gamma, cellular infiltration into the allograft, and
      graft rejection. Similarly, depletion of recipient neutrophils at the time of
      transplantation significantly extended allograft survival from day 8 to 10 in
      control-treated recipients up to day 21 after transplant. These results indicate
      the induction of highly organized cascades of neutrophil and macrophage
      chemoattractants in cardiac grafts and support the proposal that early
      inflammatory events are required for optimal recruitment of T cells into
      allografts during the progression of acute rejection of cardiac allografts.

PMID- 11509649
TI  - Deficiency in beta(2)-microglobulin, but not CD1, accelerates spontaneous lupus
      skin disease while inhibiting nephritis in MRL-Fas(lpr) nice: an example of
      disease regulation at the organ level.
AB  - When mutations that inactivate molecules that function in the immune system have
      been crossed to murine lupus strains, the result has generally been a uniform up
      regulation or down-regulation of autoimmune disease in the end organs. In the
      current work we report an interesting dissociation of target organ disease in
      beta(2)-microglobulin (beta(2)m)-deficient MRL-Fas(lpr) (MRL/lpr) mice: lupus
      skin lesions are accelerated, whereas nephritis is ameliorated. beta(2)m
      deficiency affects the expression of classical and nonclassical MHC molecules and
      thus prevents the normal development of CD8- as well as CD1-dependent NK1(+) T
      cells. To further define the mechanism by which beta(2)m deficiency accelerates
      skin disease, we studied CD1-deficient MRL/lpr mice. These mice do not have
      accelerated skin disease, excluding a CD1 or NK1(+) T cell-dependent mechanism of
      beta(2)m deficiency. The data indicate that the regulation of systemic disease is
      not solely governed by regulation of initial activation of autoreactive
      lymphocytes in secondary lymphoid tissue, as this is equally relevant to renal
      and skin diseases. Rather, regulation of autoimmunity can also occur at the
      target organ level, explaining the divergence of disease in skin and kidney in
      beta(2)m-deficient mice.

PMID- 11509650
TI  - Critical involvement of OX40 ligand signals in the T cell priming events during
      experimental autoimmune encephalomyelitis.
AB  - OX40 ligand (OX40L) expressed on APCs, and its receptor, OX40 present on
      activated T cells, are members of the TNF/TNFR family, respectively, and have
      been located at the sites of inflammatory conditions. We have observed in OX40L
      deficient mice (OX40L(-/-)) an impaired APC capacity and in our recently
      constructed transgenic mice expressing OX40L (OX40L-Tg), a markedly enhanced T
      cell response to protein Ags. Using these mice, we demonstrate here the critical
      involvement of the OX40L-OX40 interaction during the T cell priming events in the
      occurrence of experimental autoimmune encephalomyelitis (EAE). In OX40L(-/-)
      mice, abortive T cell priming greatly reduced the clinical manifestations of
      actively induced EAE, coupled with a reduction in IFN-gamma, IL-2, and IL-6
      production in vitro. Adoptive transfer experiments however revealed an efficient
      transfer of disease to OX40L(-/-) mice using wild-type donor T cells, indicating
      an intact capacity of OX40L(-/-) mice to initiate effector responses. On the
      other hand, OX40L(-/-) donor T cells failed to transfer disease to wild-type
      recipient mice. Furthermore, OX40L-Tg mice developed a greater severity of EAE
      despite a delayed onset, while both OX40L-Tg/CD28(-/-) and OX40L-Tg/CD40(-/-)
      mice failed to develop EAE demonstrating a requisite for these molecules. These
      findings indicate a pivotal role played by OX40L in the pathogenesis of EAE.

PMID- 11509651
TI  - Control of the autoimmune response by type 2 nitric oxide synthase.
AB  - Immune defense against pathogens often requires NO, synthesized by type 2 NO
      synthase (NOS2). To discern whether this axis could participate in an autoimmune
      response, we immunized NOS2-deficient mice with the autoantigen acetylcholine
      receptor, inducing muscle weakness characteristic of myasthenia gravis, a T cell
      dependent Ab-mediated autoimmune disease. We found that the acetylcholine
      receptor-immunized NOS2-deficient mice developed an exacerbated form of
      myasthenia gravis, and demonstrated that NOS2 expression limits autoreactive T
      cell determinant spreading and diversification of the autoantibody repertoire, a
      process driven by macrophages. Thus, NOS2/NO is important for silencing
      autoreactive T cells and may restrict bystander autoimmune reactions following
      the innate immune response.

PMID- 11509652
TI  - The SMRT and N-CoR corepressors are activating cofactors for histone deacetylase
      3.
AB  - Repression of gene transcription is linked to regulation of chromatin structure
      through deacetylation of core histone amino-terminal tails. This action is
      mediated by histone deacetylases (HDACs) that function within active multiprotein
      complexes directed to the promoters of repressed genes. In vivo, HDAC3 forms a
      stable complex with the SMRT corepressor. The SMRT-HDAC3 complex exhibits histone
      deacetylase activity, whereas recombinant HDAC3 is an inactive enzyme. Here we
      report that SMRT functions as an activating cofactor of HDAC3. In contrast, SMRT
      does not activate the class II HDAC4, with which it also interacts. Activation of
      HDAC3 is mediated by a deacetylase activating domain (DAD) that includes one of
      two SANT motifs present in SMRT. A cognate DAD is present in the related
      corepressor N-CoR, which can also activate HDAC3. Mutations in the DAD that
      abolish HDAC3 interaction also eliminate reconstitution of HDAC activity. Using
      purified components, the SMRT DAD is shown to be necessary and sufficient for
      activation of HDAC3. Moreover, the DAD is required both for HDAC3 to function
      enzymatically and for the major repression function of SMRT. Thus, SMRT and N-CoR
      do not serve merely as platforms for HDAC recruitment but function as an integral
      component of an active cellular HDAC3 enzyme.

PMID- 11509653
TI  - Synergistic regulation of immunoreceptor signaling by SLP-76-related adaptor Clnk
      and serine/threonine protein kinase HPK-1.
AB  - Recently, the identification of Clnk, a third member of the SLP-76 family of
      adaptors expressed exclusively in cytokine-stimulated hemopoietic cells, has been
      reported by us and by others. Like SLP-76 and Blnk, Clnk was shown to act as a
      positive regulator of immunoreceptor signaling. Interestingly, however, it did
      not detectably associate with known binding partners of SLP-76, including Vav,
      Nck, and GADS. In contrast, it became complexed in activated T cells and myeloid
      cells with an as yet unknown tyrosine-phosphorylated polypeptide of approximately
      92 kDa (p92). In order to understand better the function of Clnk, we sought to
      identify the Clnk-associated p92. Using a yeast two-hybrid screen and
      cotransfection experiments with Cos-1 cells, evidence was adduced that p92 is HPK
      1, a serine/threonine-specific protein kinase expressed in hemopoietic cells.
      Further studies showed that Clnk and HPK-1 were also associated in hemopoietic
      cells and that their interaction was augmented by immunoreceptor stimulation. A
      much weaker association was detected between HPK-1 and SLP-76. Transient
      transfections in Jurkat T cells revealed that Clnk and HPK-1 cooperated to
      increase immunoreceptor-mediated activation of the interleukin 2 (IL-2) promoter.
      Moreover, the ability of Clnk to stimulate IL-2 promoter activity could be
      blocked by expression of a kinase-defective version of HPK-1. Lastly we found
      that in spite of the differential ability of Clnk and SLP-76 to bind cellular
      proteins, Clnk was apt at rescuing immunoreceptor signaling in a Jurkat T-cell
      variant lacking SLP-76. Taken together, these results show that Clnk physically
      and functionally interacts with HPK-1 in hemopoietic cells. Moreover, they
      suggest that Clnk is capable of functionally substituting for SLP-76 in
      immunoreceptor signaling, albeit by using a distinct set of intracellular
      effectors.

PMID- 11509654
TI  - Dna damage-induced G(1) arrest in hematopoietic cells is overridden following
      phosphatidylinositol 3-kinase-dependent activation of cyclin-dependent kinase 2.
AB  - Exposure of hematopoietic cells to DNA-damaging agents induces p53-independent
      cell cycle arrest at a G(1) checkpoint. Previously, we have shown that this
      growth arrest can be overridden by cytokine growth factors, such as
      erythropoietin or interleukin-3, through activation of a phosphatidylinositol 3
      kinase (PI 3-kinase)/Akt-dependent signaling pathway. Here, we show that gamma
      irradiated murine myeloid 32D cells arrest in G(1) with active cyclin D-cyclin
      dependent kinase 4 (Cdk4) but with inactive cyclin E-Cdk2 kinases. The arrest was
      associated with elevated levels of the Cdk inhibitors p21(Cip1) and p27(Kip1),
      yet neither was associated with Cdk2. Instead, irradiation-induced inhibition of
      cyclin E-Cdk2 correlated with absence of the activating threonine-160
      phosphorylation on Cdk2. Cytokine treatment of irradiated cells induced Cdk2
      phosphorylation and activation, and cells entered into S phase despite sustained
      high-level expression of p21 and p27. Notably, the PI 3-kinase inhibitor,
      LY294002, completely blocked cytokine-induced Cdk2 activation and cell growth in
      irradiated 32D cells but not in nonirradiated cells. Together, these findings
      demonstrate a novel mechanism underlying the DNA damage-induced G(1) arrest of
      hematopoietic cells, that is, inhibition of Cdk2 phosphorylation and activation.
      These observations link PI 3-kinase signaling pathways with the regulation of
      Cdk2 activity.

PMID- 11509655
TI  - Transcriptional hyperactivity of human progesterone receptors is coupled to their
      ligand-dependent down-regulation by mitogen-activated protein kinase-dependent
      phosphorylation of serine 294.
AB  - Breast cancers often exhibit elevated expression of tyrosine kinase growth factor
      receptors; these pathways influence breast cancer cell growth in part by
      targeting steroid hormone receptors, including progesterone receptors (PR). To
      mimic activation of molecules downstream of growth factor-initiated signaling
      pathways, we overexpressed mitogen-activated protein kinase (MAPK; also known as
      extracellular signal-regulated kinase) kinase kinase 1 (MEKK1) in T47D human
      breast cancer cells expressing the B isoform of PR. MEKK1 is a strong activator
      of p42 and p44 MAPKs. MEKK1 expression increased progestin-mediated transcription
      8- to 10-fold above normal PR-driven transcription levels. This was dependent on
      the presence of a progesterone response element and functional PR. PR protein
      levels were unchanged by MEKK1 alone but were extensively down-regulated by MEKK1
      plus the progestin R5020. MEKK1 expression resulted in phosphorylation of PR on
      Ser294, a MAPK consensus site known to mediate ligand-dependent PR degradation.
      MEK inhibitors blocked phosphorylation of Ser294 and attenuated PR
      transcriptional hyperactivity in response to MEKK1 plus R5020; stabilization of
      PR by inhibition of the 26S proteasome produced similar results. T47D cells
      stably expressing mutant S294A PR, in which serine 294 is replaced by alanine,
      fail to undergo ligand-dependent down-regulation and are resistant to MEKK1-plus
      R5020-induced transcriptional synergy but respond to progestins alone. Similarly,
      c-myc protein levels are synergistically increased by epidermal growth factor and
      R5020 in cells expressing wild-type PR, but not S294A PR. Thus, highly stable
      mutant PR are functional in response to progestins but are incapable of cross
      talk with MAPK-driven pathways. These studies demonstrate a paradoxical coupling
      between steroid receptor down-regulation and transcriptional hyperactivity. They
      also suggest a link between phosphorylation of PR by MAPKs in response to peptide
      growth factor signaling and steroid hormone control of breast cancer cell growth.

PMID- 11509656
TI  - The essential function of the small Tim proteins in the TIM22 import pathway does
      not depend on formation of the soluble 70-kilodalton complex.
AB  - The TIM22 protein import pathway of the yeast mitochondrion contains several
      components, including a family of five proteins (Tim8p, -9p, -10p, -12p, and -13p
      [Tim, for translocase of inner membrane]) that are located in the intermembrane
      space and are 25% identical. Tim9p and Tim10p have dual roles in mediating the
      import of inner membrane proteins. Like the Tim8p-Tim13p complex, the Tim9p
      Tim10p complex functions as a putative chaperone to guide hydrophobic precursors
      across the intermembrane space. Like membrane-associated Tim12p, they are members
      of the Tim18p-Tim22p-Tim54p membrane complex that mediates precursor insertion
      into the membrane. To understand the role of this family in protein import, we
      have used a genetic approach to manipulate the complement of the small Tim
      proteins. A strain has been constructed that lacks the 70-kDa soluble Tim8p
      Tim13p and Tim9p-Tim10p complexes in the intermembrane space. Instead, a
      functional version of Tim9p (Tim9(S67C)p), identified as a second-site suppressor
      of a conditional tim10 mutant, maintains viability. Characterization of this
      strain revealed that Tim9(S67C)p and Tim10p were tightly associated with the
      inner membrane, the soluble 70-kDa Tim8p-Tim13p and Tim9p-Tim10p complexes were
      not detectable, and the rate of protein import into isolated mitochondria
      proceeded at a slower rate. An arrested translocation intermediate bound to
      Tim9(S67C)p was located in the intermembrane space, associated with the inner
      membrane. We suggest that the 70-kDa complexes facilitate import, similar to the
      outer membrane receptors of the TOM (hetero-oligomeric translocase of the outer
      membrane) complex, and the essential role of Tim9p and Tim10p may be to mediate
      protein insertion in the inner membrane with the TIM22 complex.

PMID- 11509657
TI  - Regulation of the yeast Yap1p nuclear export signal is mediated by redox signal
      induced reversible disulfide bond formation.
AB  - Yap1p, a crucial transcription factor in the oxidative stress response of
      Saccharomyces cerevisiae, is transported in and out of the nucleus under
      nonstress conditions. The nuclear export step is specifically inhibited by
      H(2)O(2) or the thiol oxidant diamide, resulting in Yap1p nuclear accumulation
      and induction of transcription of its target genes. Here we provide evidence for
      sensing of H(2)O(2) and diamide mediated by disulfide bond formation in the C
      terminal cysteine-rich region (c-CRD), which contains 3 conserved cysteines and
      the nuclear export signal (NES). The H(2)O(2) or diamide-induced oxidation of the
      c-CRD in vivo correlates with induced Yap1p nuclear localization. Both were
      initiated within 1 min of application of oxidative stress, before the
      intracellular redox status of thioredoxin and glutathione was affected. The
      cysteine residues in the middle region of Yap1p (n-CRD) are required for
      prolonged nuclear localization of Yap1p in response to H(2)O(2) and are thus also
      required for maximum transcriptional activity. Using mass spectrometry analysis,
      the H(2)O(2)-induced oxidation of the c-CRD in vitro was detected as an
      intramolecular disulfide linkage between the first (Cys(598)) and second
      (Cys(620)) cysteine residues; this linkage could be reduced by thioredoxin. In
      contrast, diamide induced each pair of disulfide linkage in the c-CRD, but in
      this case the cysteine residues in the n-CRD appeared to be dispensable for the
      response. Our data provide evidence for molecular mechanisms of redox signal
      sensing through the thiol-disulfide redox cycle coupled with the thioredoxin
      system in the Yap1p NES.

PMID- 11509658
TI  - Functional multimerization of the human telomerase reverse transcriptase.
AB  - The telomerase enzyme exists as a large complex (approximately 1,000 kDa) in
      mammals and at minimum is composed of the telomerase RNA and the catalytic
      subunit telomerase reverse transcriptase (TERT). In Saccharomyces cerevisiae,
      telomerase appears to function as an interdependent dimer or multimer in vivo (J.
      Prescott and E. H. Blackburn, Genes Dev. 11:2790-2800, 1997). However, the
      requirements for multimerization are not known, and it remained unclear whether
      telomerase exists as a multimer in other organisms. We show here that human TERT
      (hTERT) forms a functional multimer in a rabbit reticulocyte lysate
      reconstitution assay and in human cell extracts. Two separate, catalytically
      inactive TERT proteins can complement each other in trans to reconstitute
      catalytic activity. This complementation requires the amino terminus of one hTERT
      and the reverse transcriptase and C-terminal domains of the second hTERT. The
      telomerase RNA must associate with only the latter hTERT for reconstitution of
      telomerase activity to occur. Multimerization of telomerase also facilitates the
      recognition and elongation of substrates in vitro and in vivo. These data suggest
      that the catalytic core of human telomerase may exist as a functionally
      cooperative dimer or multimer in vivo.

PMID- 11509659
TI  - MGA2 is involved in the low-oxygen response element-dependent hypoxic induction
      of genes in Saccharomyces cerevisiae.
AB  - Eukaryotes have the ability to respond to changes in oxygen tension by
      alterations in gene expression. For example, OLE1 expression in Saccharomyces
      cerevisiae is upregulated under hypoxic conditions. Previous studies have
      suggested that the pathway regulating OLE1 expression by unsaturated fatty acids
      may involve Mga2p and Spt23p, two structurally and functionally related proteins.
      To define the possible roles of each of these genes on hypoxia-induced OLE1
      expression, we examined OLE1 expression under normoxia, hypoxia, and cobalt
      treatment conditions in Deltamga2 or Deltaspt23 deletion strains. The results of
      OLE1 promoter-lacZ reporter gene and Northern blot analyses showed that hypoxia-
      and cobalt-induced OLE1 expression was dramatically decreased in a Deltamga2
      strain but not in a Deltaspt23 strain. Further analyses using low-oxygen response
      element (LORE)-CYC1-lacZ fusion reporter assays and electrophoretic mobility
      shift assays (EMSAs) demonstrated that MGA2 significantly affects the LORE
      dependent hypoxic induction pathway of gene expression. When MGA2 was supplied by
      a plasmid, the LORE-dependent hypoxia-inducible reporter expression was
      recovered, as was the hypoxia-inducible complex in EMSAs in the S. cerevisiae
      Deltamga2 strain. Supershift analysis of EMSAs using crude extracts containing
      mycMga2p indicated that Mga2p is a component of the LORE-binding complex. Another
      LORE-dependent, hypoxia-inducible gene, ATF1, was similarly affected in the
      Deltamga2 strain. These results indicate that MGA2 is required for the LORE
      dependent hypoxic gene induction in S. cerevisiae.

PMID- 11509660
TI  - A point mutation in the N-terminal coiled-coil domain releases c-Fes tyrosine
      kinase activity and survival signaling in myeloid leukemia cells.
AB  - The c-fes locus encodes a 93-kDa non-receptor protein tyrosine kinase (Fes) that
      regulates the growth and differentiation of hematopoietic and vascular
      endothelial cells. Unique to Fes is a long N-terminal sequence with two regions
      of strong homology to coiled-coil oligomerization domains. We introduced leucine
      to-proline substitutions into the coiled coils that were predicted to disrupt the
      coiled-coil structure. The resulting mutant proteins, together with wild-type
      Fes, were fused to green fluorescent protein and expressed in Rat-2 fibroblasts.
      We observed that a point mutation in the first coiled-coil domain (L145P)
      dramatically increased Fes tyrosine kinase and transforming activities in this
      cell type. In contrast, a similar point mutation in the second coiled-coil motif
      (L334P) was without effect. However, combining the L334P and L145P mutations
      reduced transforming and kinase activities by approximately 50% relative to the
      levels of activity produced with the L145P mutation alone. To study the effects
      of the coiled-coil mutations in a biologically relevant context, we expressed the
      mutant proteins in the granulocyte-macrophage colony-stimulating factor (GM-CSF)
      dependent myeloid leukemia cell line TF-1. In this cellular context, the L145P
      mutation induced GM-CSF independence, cell attachment, and spreading. These
      effects correlated with a marked increase in L145P protein autophosphorylation
      relative to that of wild-type Fes. In contrast, the double coiled-coil mutant
      protein showed greatly reduced kinase and biological activities in TF-1 cells.
      These data are consistent with a role for the first coiled coil in the negative
      regulation of kinase activity and a requirement for the second coiled coil in
      either oligomerization or recruitment of signaling partners. Gel filtration
      experiments showed that the unique N-terminal region interconverts between
      monomeric and oligomeric forms. Single point mutations favored oligomerization,
      while the double point mutant protein eluted essentially as the monomer. These
      data provide new evidence for coiled-coil-mediated regulation of c-Fes tyrosine
      kinase activity and signaling, a mechanism unique among tyrosine kinases.

PMID- 11509661
TI  - Acetylation of nuclear hormone receptor-interacting protein RIP140 regulates
      binding of the transcriptional corepressor CtBP.
AB  - CtBP (carboxyl-terminal binding protein) participates in regulating cellular
      development and differentiation by associating with a diverse array of
      transcriptional repressors. Most of these interactions occur through a consensus
      CtBP-binding motif, PXDLS, in the repressor proteins. We previously showed that
      the CtBP-binding motif in E1A is flanked by a Lys residue and suggested that
      acetylation of this residue by the p300/CBP-associated factor P/CAF disrupts the
      CtBP interaction. In this study, we show that the interaction between CtBP and
      the nuclear hormone receptor corepressor RIP140 is regulated similarly, in this
      case by p300/CBP itself. CtBP was shown to interact with RIP140 in vitro and in
      vivo through a sequence, PIDLSCK, in the amino-terminal third of the RIP140
      protein. Acetylation of the Lys residue in this motif, demonstrated in vivo by
      using an acetylated RIP140-specific antibody, dramatically reduced CtBP binding.
      Mutation of the Lys residue to Gln resulted in a decrease in CtBP binding in vivo
      and a loss of transcriptional repression. We suggest that p300/CBP-mediated
      acetylation disrupts the RIP140-CtBP complex and derepresses nuclear hormone
      receptor-regulated genes. Disruption of repressor-CtBP interactions by
      acetylation may be a general mode of gene activation.

PMID- 11509662
TI  - Functional analysis of Asb-1 using genetic modification in mice.
AB  - The Asbs are a family of ankyrin repeat proteins that, along with four other
      protein families, contain a C-terminal SOCS box motif, which was first identified
      in the suppressor of cytokine signaling (SOCS) proteins. While it is clear that
      the SOCS proteins are involved in the negative regulation of cytokine signaling,
      the biological roles of the other SOCS box-containing families are unknown. We
      have investigated Asb-1 function by generating mice that lack this protein, as
      well as mice that overexpress full-length or truncated Asb-1 in a wide range of
      tissues. Although Asb-1 is expressed in multiple organs, including the
      hematopoietic compartment in wild-type mice, Asb-1(-/-) mice develop normally and
      exhibit no anomalies of mature blood cells or their progenitors. While most
      organs in these mice appear normal, the testes of Asb-1(-/-) mice display a
      diminution of spermatogenesis with less complete filling of seminiferous tubules.
      In contrast, the widespread overexpression of Asb-1 in the mouse has no apparent
      deleterious effects.

PMID- 11509663
TI  - Cell cycle progression and cell polarity require sphingolipid biosynthesis in
      Aspergillus nidulans.
AB  - Sphingolipids are major components of the plasma membrane of eukaryotic cells and
      were once thought of merely as structural components of the membrane. We have
      investigated effects of inhibiting sphingolipid biosynthesis, both in germinating
      spores and growing hyphae of Aspergillus nidulans. In germinating spores, genetic
      or pharmacological inactivation of inositol phosphorylceramide (IPC) synthase
      arrests the cell cycle in G(1) and also prevents polarized growth during spore
      germination. However, inactivation of IPC synthase not only eliminates
      sphingolipid biosynthesis but also leads to a marked accumulation of ceramide,
      its upstream intermediate. We therefore inactivated serine palmitoyltransferase,
      the first enzyme in the sphingolipid biosynthesis pathway, to determine effects
      of inhibiting sphingolipid biosynthesis without an accumulation of ceramide. This
      inactivation also prevented polarized growth but did not affect nuclear division
      of germinating spores. To see if sphingolipid biosynthesis is required to
      maintain polarized growth, and not just to establish polarity, we inhibited
      sphingolipid biosynthesis in cells in which polarity was already established.
      This inhibition rapidly abolished normal cell polarity and promoted cell tip
      branching, which normally never occurs. Cell tip branching was closely associated
      with dramatic changes in the normally highly polarized actin cytoskeleton and
      found to be dependent on actin function. The results indicate that sphingolipids
      are essential for the establishment and maintenance of cell polarity via control
      of the actin cytoskeleton and that accumulation of ceramide is likely responsible
      for arresting the cell cycle in G(1).

PMID- 11509664
TI  - Xenopus U3 snoRNA GAC-Box A' and Box A sequences play distinct functional roles
      in rRNA processing.
AB  - Mutations in the 5' portion of Xenopus U3 snoRNA were tested for function in
      oocytes. The results revealed a new cleavage site (A0) in the 3' region of
      vertebrate external transcribed spacer sequences. In addition, U3 mutagenesis
      uncoupled cleavage at sites 1 and 2, flanking the 5' and 3' ends of 18S rRNA, and
      generated novel intermediates: 19S and 18.5S pre-rRNAs. Furthermore, specific
      nucleotides in Xenopus U3 snoRNA that are required for cleavages in pre-rRNA were
      identified: box A is essential for site A0 cleavage, the GAC-box A' region is
      necessary for site 1 cleavage, and the 3' end of box A' and flanking nucleotides
      are required for site 2 cleavage. Differences between metazoan and yeast U3
      snoRNA-mediated rRNA processing are enumerated. The data support a model where
      metazoan U3 snoRNA acts as a bridge to draw together the 5' and 3' ends of the
      18S rRNA coding region within pre-rRNA to coordinate their cleavage.

PMID- 11509665
TI  - Nuclear localization of CBF1 is regulated by interactions with the SMRT
      corepressor complex.
AB  - The CSL family protein CBF1 is a nuclear mediator of Notch signaling and has been
      predicted to contain an N-terminal nuclear localization signal in exon 4.
      Surprisingly, we found that CBF1 carrying mutations at codon 233 or 249 within
      exon 7 was restricted to the cytoplasm. In mammalian and yeast two-hybrid assays,
      these mutations were also associated with a loss of CBF1-mediated transcriptional
      repression and a severely impaired interaction with the corepressors SMRT and
      CIR. Overexpression of SMRT rescued the ability of mutant CBF1 to target to the
      nucleus of transfected cells and similarly rescued nuclear targeting of enhanced
      green fluorescent protein (EGFP)-CBF1 exons 6 to 9 CBF1(6-9)carrying the codon
      233 or 249 mutations. Carboxy-terminally truncated SMRT with amino acids (aa)
      1291 to 1495 deleted was unable to rescue the nuclear targeting of mutant EGFP
      CBF1(6-9). In yeast two-hybrid assays, the SMRT aa 1291 to 1495 domain interacted
      with SKIP and SMRT aa 1291 to 1495 colocalized with SKIP within the nuclei of
      cotransfected cells. Comparison of the intracellular localization of CBF1(6-9)
      with that of CBF1(5-9) further supported the suggestion that nuclear targeting of
      CBF1 is dependent on the formation of a CBF1-SMRT-SKIP corepressor complex. These
      observations suggest that nuclear targeting of CBF1 is itself a component of CBF1
      mediated gene regulation and that in the absence of signaling, CBF1 enters the
      nucleus precommitted to a transcriptional repression function. The activators
      NotchIC (the intracellular domain of Notch) and Epstein-Barr virus EBNA2 also
      mediated nuclear targeting of mutant CBF1, consistent with the competition model
      for activator versus corepressor binding to CBF1.

PMID- 11509666
TI  - Targeting of the c-Abl tyrosine kinase to mitochondria in endoplasmic reticulum
      stress-induced apoptosis.
AB  - The ubiquitously expressed c-Abl tyrosine kinase localizes to the nucleus and
      cytoplasm. Using confocal microscopy, we demonstrated that c-Abl colocalizes with
      the endoplasmic reticulum (ER)-associated protein grp78. Expression of c-Abl in
      the ER was confirmed by immunoelectron microscopy. Subcellular fractionation
      studies further indicate that over 20% of cellular c-Abl is detectable in the ER.
      The results also demonstrate that induction of ER stress with calcium ionophore
      A23187, brefeldin A, or tunicamycin is associated with translocation of ER
      associated c-Abl to mitochondria. In concert with targeting of c-Abl to
      mitochondria, cytochrome c is released in the response to ER stress by a c-Abl
      dependent mechanism, and ER stress-induced apoptosis is attenuated in c-Abl
      deficient cells. These findings indicate that c-Abl is involved in signaling from
      the ER to mitochondria and thereby the apoptotic response to ER stress.

PMID- 11509667
TI  - Candida tropicalis Etr1p and Saccharomyces cerevisiae Ybr026p (Mrf1'p), 2-enoyl
      thioester reductases essential for mitochondrial respiratory competence.
AB  - We report here on the identification and characterization of novel 2-enoyl
      thioester reductases of fatty acid metabolism, Etr1p from Candida tropicalis and
      its homolog Ybr026p (Mrf1'p) from Saccharomyces cerevisiae. Overexpression of
      these proteins in S. cerevisiae led to the development of significantly enlarged
      mitochondria, whereas deletion of the S. cerevisiae YBR026c gene resulted in
      rudimentary mitochondria with decreased contents of cytochromes and a respiration
      deficient phenotype. Immunolocalization and in vivo targeting experiments showed
      these proteins to be predominantly mitochondrial. Mitochondrial targeting was
      essential for complementation of the mutant phenotype, since targeting of the
      reductases to other subcellular locations failed to reestablish respiratory
      growth. The mutant phenotype was also complemented by a mitochondrially targeted
      FabI protein from Escherichia coli. FabI represents a nonhomologous 2-enoyl-acyl
      carrier protein reductase that participates in the last step of the type II fatty
      acid synthesis. This indicated that 2-enoyl thioester reductase activity was
      critical for the mitochondrial function. We conclude that Etr1p and Ybr026p are
      novel 2-enoyl thioester reductases required for respiration and the maintenance
      of the mitochondrial compartment, putatively acting in mitochondrial synthesis of
      fatty acids.

PMID- 11509668
TI  - Tumor-specific proteolytic processing of cyclin E generates hyperactive lower
      molecular-weight forms.
AB  - Cyclin E is a G(1) cyclin essential for S-phase entry and has a profound role in
      oncogenesis. Previously this laboratory found that cyclin E is overexpressed and
      present in lower-molecular-weight (LMW) isoforms in breast cancer cells and tumor
      tissues compared to normal cells and tissues. Such alteration of cyclin E is
      linked to poor patient outcome. Here we report that the LMW forms of cyclin E are
      hyperactive biochemically and they can more readily induce G(1)-to-S progression
      in transfected normal cells than the full-length form of the protein can. Through
      biochemical and mutational analyses we have identified two proteolytically
      sensitive sites in the amino terminus of human cyclin E that are cleaved to
      generate the LMW isoforms found in tumor cells. Not only are the LMW forms of
      cyclin E functional, as they phosphorylate substrates such as histone H1 and GST
      Rb, but also their activities are higher than the full-length cyclin E. These
      nuclear localized LMW forms of cyclin E are also biologically functional, as
      their overexpression in normal cells increases the ability of these cells to
      enter S and G(2)/M. Lastly, we show that cyclin E is selectively cleaved in vitro
      by the elastase class of serine proteases to generate LMW forms similar to those
      observed in tumor cells. These studies suggest that the defective entry into and
      exit from S phase by tumor cells is in part due to the proteolytic processing of
      cyclin E, which generates hyperactive LMW isoforms whose activities have been
      modified from that of the full-length protein.

PMID- 11509669
TI  - H2A.Z is required for global chromatin integrity and for recruitment of RNA
      polymerase II under specific conditions.
AB  - Evolutionarily conserved variant histone H2A.Z has been recently shown to
      regulate gene transcription in Saccharomyces cerevisiae. Here we show that loss
      of H2A.Z in this organism negatively affects the induction of GAL genes.
      Importantly, fusion of the H2A.Z C-terminal region to S phase H2A without its
      corresponding C-terminal region can mediate the variant histone's specialized
      function in GAL1-10 gene induction, and it restores the slow-growth phenotype of
      cells with a deletion of HTZ1. Furthermore, we show that the C-terminal region of
      H2A.Z can interact with some components of the transcriptional apparatus. In
      cells lacking H2A.Z, recruitment of RNA polymerase II and TATA-binding protein to
      the GAL1-10 promoters is significantly diminished under inducing conditions.
      Unexpectedly, we also find that H2A.Z is required to globally maintain chromatin
      integrity under GAL gene-inducing conditions. We hypothesize that H2A.Z can
      positively regulate gene transcription, at least in part, by modulating
      interactions with RNA polymerase II-associated factors at certain genes under
      specific cell growth conditions.

PMID- 11509670
TI  - RotundRacGAP functions with Ras during spermatogenesis and retinal
      differentiation in Drosophila melanogaster.
AB  - Our analysis of rotund (rn) null mutations in Drosophila melanogaster revealed
      that deletion of the rn locus affects both spermatid and retinal differentiation.
      In the male reproductive system, the absence of RnRacGAP induced small testes,
      empty seminal vesicles, short testicular cysts, reduced amounts of interspermatid
      membrane, the absence of individualization complexes, and incomplete
      mitochondrial condensation. Flagellar growth continued within the short rn null
      cysts to produce large bulbous terminations of intertwined mature flagella.
      Organization of the retina was also severely perturbed as evidenced by grossly
      misshapen ommatidia containing reduced numbers of photoreceptor and pigment
      cells. These morphological phenotypes were rescued by genomic rnRacGAP
      transgenes, demonstrating that RnRacGAP function is critical to spermatid and
      retinal differentiation. The testicular phenotypes were suppressed by
      heterozygous hypomorphic mutations in the Dras1 and drk genes, indicating cross
      talk between RacGAP-regulated signaling and that of the Ras pathway. The observed
      genetic interactions are consistent with a model in which Rac signaling is
      activated by Ras and negatively regulated by RnRacGAP during spermatid
      differentiation. RnRacGAP and Ras cross talk also operated during retinal
      differentiation; however, while the heterozygous hypomorphic drk mutation
      continued to act as a suppressor of the rn null mutation, the heterozygous
      hypomorphic Dras1 mutation induced novel retinal phenotypes.

PMID- 11509671
TI  - Mechanisms controlling subcellular localization of the G(1) cyclins Cln2p and
      Cln3p in budding yeast.
AB  - Different G(1) cyclins confer functional specificity to the cyclin-dependent
      kinase (Cdk) Cdc28p in budding yeast. The Cln3p G(1) cyclin is localized
      primarily to the nucleus, while Cln2p is localized primarily to the cytoplasm.
      Both binding to Cdc28p and Cdc28p-dependent phosphorylation in the C-terminal
      region of Cln2p are independently required for efficient nuclear depletion of
      Cln2p, suggesting that this process may be physiologically regulated. The
      accumulation of hypophosphorylated Cln2 in the nucleus is an energy-dependent
      process, but may not involve the RAN GTPase. Phosphorylation of Cln2p is
      inefficient in small newborn cells obtained by elutriation, and this lowered
      phosphorylation correlates with reduced Cln2p nuclear depletion in newborn cells.
      Thus, Cln2p may have a brief period of nuclear residence early in the cell cycle.
      In contrast, the nuclear localization pattern of Cln3p is not influenced by Cdk
      activity. Cln3p localization requires a bipartite nuclear localization signal
      (NLS) located at the C terminus of the protein. This sequence is required for
      nuclear localization of Cln3p and is sufficient to confer nuclear localization to
      green fluorescent protein in a RAN-dependent manner. Mislocalized Cln3p, lacking
      the NLS, is much less active in genetic assays specific for Cln3p, but more
      active in assays normally specific for Cln2p, consistent with the idea that Cln3p
      localization explains a significant part of Clnp functional specificity.

PMID- 11509672
TI  - Identification of a signal-responsive nuclear export sequence in class II histone
      deacetylases.
AB  - Activation of muscle-specific genes by the MEF2 transcription factor is inhibited
      by class II histone deacetylases (HDACs) 4 and 5, which contain carboxy-terminal
      deacetylase domains and amino-terminal extensions required for association with
      MEF2. The inhibitory action of HDACs is overcome by myogenic signals which
      disrupt MEF2-HDAC interactions and stimulate nuclear export of these
      transcriptional repressors. Nucleocytoplasmic trafficking of HDAC5 is mediated by
      binding of the chaperone protein 14-3-3 to two phosphoserine residues (Ser-259
      and Ser-498) in its amino-terminal extension. Here we show that HDAC4 and -5 each
      contain a signal-responsive nuclear export sequence (NES) at their extreme
      carboxy termini. The NES is conserved in another class II HDAC, HDAC7, but is
      absent in class I HDACs and the HDAC-related corepressor, MEF2-interacting
      transcription repressor. Our results suggest that this conserved NES is inactive
      in unphosphorylated HDAC5, which is localized to the nucleus, and that calcium
      calmodulin-dependent protein kinase (CaMK)-dependent binding of 14-3-3 to
      phosphoserines 259 and 498 activates the NES, with consequent export of the
      transcriptional repressor to the cytoplasm. A single amino acid substitution in
      this NES is sufficient to retain HDAC5 in the nucleus in the face of CaMK
      signaling. These findings provide molecular insight into the mechanism by which
      extracellular cues alter chromatin structure to promote muscle differentiation
      and other MEF2-regulated processes.

PMID- 11509673
TI  - Cytochrome p450 epoxygenase metabolism of arachidonic acid inhibits apoptosis.
AB  - The ubiquitous cytochrome P450 hemoproteins play important functional roles in
      the metabolism and detoxification of foreign chemicals. However, other than
      established roles in cholesterol catabolism and steroid hormone biosynthesis,
      their cellular and/or organ physiological functions remain to be fully
      characterized. Here we show that the cytochrome P450 epoxygenase arachidonic acid
      metabolite 14,15-epoxyeicosatrienoic acid (14,15-EET) inhibits apoptosis induced
      by serum withdrawal, H(2)O(2), etoposide, or excess free arachidonic acid (AA),
      as determined by DNA laddering, Hoechst staining, and fluorescein isothiocyanate
      labeled annexin V binding. In the stable transfectants (BM3 cells) expressing a
      mutant bacterial P450 AA epoxygenase, F87V BM3, which was genetically engineered
      to metabolize arachidonic acid only to 14,15-EET, AA did not induce apoptosis and
      protected against agonist-induced apoptosis. Ceramide assays demonstrated
      increased AA-induced ceramide production within 1 h and elevated ceramide levels
      for up to 48 h, the longest time tested, in empty-vector-transfected cells
      (Vector cells) but not in BM3 cells. Inhibition of cytochrome P450 activity by 17
      octadecynoic acid restored AA-induced ceramide production in BM3 cells. Exogenous
      C2-ceramide markedly increased apoptosis in quiescent Vector cells as well as BM3
      cells, and apoptosis was prevented by pretreatment of Vector cells with exogenous
      14,15-EET and by pretreatment of BM3 cells with AA. The ceramide synthase
      inhibitor fumonisin B1 did not affect AA-induced ceramide production and
      apoptosis; in contrast, these effects of AA were blocked by the neutral
      sphingomyelinase inhibitor scyphostatin. The pan-caspase inhibitor Z-VAD-fmk had
      no effect on AA-induced ceramide generation but abolished AA-induced apoptosis.
      The antiapoptotic effects of 14,15-EET were blocked by two mechanistically and
      structurally distinct phosphatidylinositol-3 (PI-3) kinase inhibitors, wortmannin
      and LY294002, but not by the specific mitogen-activated protein kinase kinase
      inhibitor PD98059. Immunoprecipitation followed by an in vitro kinase assay
      revealed activation of Akt kinase within 10 min after 14,15-EET addition, which
      was completely abolished by either wortmannin or LY294002 pretreatment. In
      summary, the present studies demonstrated that 14,15-EET inhibits apoptosis by
      activation of a PI-3 kinase-Akt signaling pathway. Furthermore, cytochrome P450
      epoxygenase promotes cell survival both by production of 14,15-EET and by
      metabolism of unesterified AA, thereby preventing activation of the neutral
      sphingomyelinase pathway and proapoptotic ceramide formation.

PMID- 11509677
TI  - The role of macrophages in glomerulonephritis.
AB  - Macrophage accumulation is a prominent feature in most types of human
      glomerulonephritis. In particular, tubulointerstitial macrophage accumulation
      correlates with the degree of renal dysfunction and is predictive of disease
      progression. Depletion studies have shown that macrophages can induce glomerular
      injury in experimental glomerulonephritis. Moreover, recent studies targeting
      chemokines and adhesion molecules have shown that inhibiting macrophage
      accumulation can suppress progressive renal injury in animal models of
      glomerulonephritis. Macrophages can produce many molecules with the potential to
      cause renal damage, although the precise mechanism(s) of macrophage-mediated
      renal injury have yet to be determined. It is now evident that tubules-a major
      source of chemokines and adhesion molecules-play an active role in promoting
      interstitial macrophage infiltration and activation. Thus, targeting pro
      inflammatory functions of tubular epithelial cells may be an effective means to
      inhibit macrophage-mediated tubulointerstitial injury without causing systemic
      immunosuppression.

PMID- 11509674
TI  - S phase-specific proteolytic cleavage is required to activate stable DNA binding
      by the CDP/Cut homeodomain protein.
AB  - The CCAAT displacement protein (CDP), the homologue of the Drosophila
      melanogaster Cut protein, contains four DNA binding domains that function in
      pairs. Cooperation between Cut repeat 3 and the Cut homeodomain allows stable DNA
      binding to the ATCGAT motif, an activity previously shown to be upregulated in S
      phase. Here we showed that the full-length CDP/Cut protein is incapable of stable
      DNA binding and that the ATCGAT binding activity present in cells involves a 110
      kDa carboxy-terminal peptide of CDP/Cut. A vector expressing CDP/Cut with Myc and
      hemagglutinin epitope tags at either end generated N- and C-terminal products of
      90 and 110 kDa, suggesting that proteolytic cleavage was involved. In vivo
      pulse/chase labeling experiments confirmed that the 110-kDa protein was derived
      from the full-length CDP/Cut protein. Proteolytic processing was weak or not
      detectable in G(0) and G(1) but increased in populations of cells enriched in S
      phase, and the appearance of the 110-kDa protein coincided with the increase in
      ATCGAT DNA binding. Interestingly, the amino-truncated and the full-length
      CDP/Cut isoforms exhibited different transcriptional properties in a reporter
      assay. We conclude that proteolytic processing of CDP/Cut at the G(1)/S
      transition generates a CDP/Cut isoform with distinct DNA binding and
      transcriptional activities. These findings, together with the cleavage of the
      Scc1 protein at mitosis, suggest that site-specific proteolysis may play an
      important role in the regulation of cell cycle progression.

PMID- 11509675
TI  - Promotion of cell cycle progression by basic helix-loop-helix E2A.
AB  - Normal B-cell development requires the E2A gene and its encoded transcription
      factors E12 and E47. Current models predict that E2A promotes cell
      differentiation and inhibits G(1) cell cycle progression. The latter raises the
      conundrum of how B cells proliferate while expressing high levels of E2A protein.
      To study the relationship between E2A and cell proliferation, we established a
      tissue culture-based model in which the activity of E2A can be modulated in an
      inducible manner using E47R, an E47-estrogen fusion construct, and E47ERT, a
      dominant negative E47-estrogen fusion construct. The two constructs were
      subcloned into retroviral vectors and expressed in the human pre-B-cell line 697,
      the human myeloid progenitor cell line K562, and the murine fibroblastic cell
      line NIH 3T3. In both B cells and non-B cells, suppression of E2A activity by
      E47ERT inhibited G(1) progression and was associated with decreased expression of
      multiple cyclins including the G(1)-phase cyclin D2 and cyclin D3. Consistent
      with these findings, E2A null mice expressed decreased levels of cyclin D2 and
      cyclin D3 transcripts. In complementary experiments, ectopic expression of E47R
      promoted G(1) progression and was associated with increased levels of multiple
      cyclins, including cyclin D2 and cyclin D3. The induction of some cyclin
      transcripts occurred even in the absence of protein synthesis. We conclude that,
      in some cells, E2A can promote cell cycle progression, contrary to the present
      view that E2A inhibits G(1) progression.

PMID- 11509678
TI  - Treatment of membranous nephropathy.
AB  - Several therapeutic approaches have been tried in patients with membranous
      nephropathy. Corticosteroids have been largely used, but a meta-analysis of the
      available controlled trials did not show any benefit of corticosteroids either in
      favouring remission of the nephrotic syndrome or in preventing renal dysfunction.
      Controversial results have been obtained with cytotoxic agents. Unfortunately,
      most of the available trials were small in size and had short-term follow-ups.
      Three controlled trials evaluated the role of a 6-month treatment with
      methylprednisolone and chlorambucil. The first trial showed that the 10-year
      renal survival rate was 92% in treated patients compared with 60% in untreated
      controls. A second trial compared the effects of methylprednisolone/chlorambucil
      with those of methylprednisolone alone. The combined treatment achieved remission
      of nephrotic syndrome in 64% of cases vs 38% in patients given steroids alone. A
      third trial showed equivalent results in patients randomized to be given
      methylprednisolone/chlorambucil or methylprednisolone/cyclophosphamide. A number
      of non-controlled studies and a randomized trial also showed the efficacy of
      cyclosporine in reducing proteinuria. In many but not all cases, proteinuria
      reappeared when cyclosporine was stopped. In conclusion, although the treatment
      of membranous nephropathy remains difficult, some therapeutical approaches have
      proved to favour remission and protect renal function

PMID- 11509679
TI  - Renal disease in type 2 diabetes.
AB  - The prevalence of type 2 diabetes is rising in all Westernized societies.
      Presumably as a consequence of diminishing cardiovascular mortality, end-stage
      renal failure (ESRF) in patients with diabetes (mostly type 2) as a co-morbid
      condition has risen dramatically in the past decade. This constellation has
      become the single most common cause of ESRF in most countries. Such an
      epidemiological trend is particularly regrettable, since in uraemic diabetic
      patients, medical rehabilitation and survival are remarkably poor. Recent studies
      indicate that an interplay between genetic predisposition and factors, some of
      them susceptible to intervention, such as hyperglycaemia, blood pressure,
      smoking, age, gender and ethnicity, predispose to the development and progression
      of nephropathy. It has also become clear that trace albuminuria
      ('microalbuminuria') provides unique opportunities to recognize incipient renal
      involvement early on, although it is less specific in type 2 as compared with
      type 1 diabetes. Factors that promote progression include hypertension,
      proteinuria, smoking, glycaemic control and, less certainly, dietary protein
      intake and hyperlipidaemia. Cumulating evidence indicates that early intervention
      delays progression of nephropathy. The most important strategies to combat the
      medical catastrophe of increasing numbers of diabetic patients with ESRF include:
      (i) prevention of diabetes (mainly type 2); (ii) glycaemic control to prevent
      onset of renal involvement; and (iii) meticulous antihypertensive treatment to
      avoid progression of nephropathy.

PMID- 11509680
TI  - Pharmacological intervention in progressive renal diseases.

PMID- 11509681
TI  - Gene therapy approach in renal disease in the 21st century.
AB  - Theoretically, gene therapy has distinct potential to treat renal disease at the
      most fundamental level. However, the ability to pursue gene therapy has been
      limited by the availability of an adequate system for gene delivery to the
      kidney. The present viral vector systems seem to have limitations for clinical
      use because of uncertainty regarding their toxicity and immunogenicity; however,
      adenovirus-mediated gene transfer succeeded in gene expression in the kidney.
      Adeno-associated virus has a potential to be utilized as a vector targeting both
      kidney and skeletal muscle. Given that the systemic delivery of the functional
      protein can serve for the therapy of the renal diseases, skeletal muscle
      targeting gene therapy might be an alternative strategy for treatment of renal
      disease. Non-viral vectors such as the haemagglutinating virus of Japan (HVJ)
      liposome method and cationic liposome are possibilities, but their efficiency
      needs to be improved. Electric pulse is emerging as a new and less harmful
      strategy of gene transfer to various tissues, including the kidney. I believe
      that two plausible strategies exist for the therapeutic use of gene transfer in
      the near future: skeletal muscle-targeting gene therapy and kidney
      transplantation. Application of gene therapy to the transplanted kidney may
      potentially improve graft outcome by reducing acute and chronic rejections. The
      emerging strategies of gene transfer in kidneys are reviewed and the potential
      application of gene therapy in renal diseases are discussed.

PMID- 11509682
TI  - Erythropoietin and iron: the role of ascorbic acid.
AB  - Provision of sufficient available iron is a prerequisite to ensure the optimal
      response to recombinant human erythropoietin (rHuEpo). Functional iron deficiency
      (a state when iron supply is reduced to meet the demands for increased
      erythropoiesis) is the common cause of rHuEpo hyporesponsiveness in dialysis
      patients who have normal iron status, even when they are iron-overloaded. Iron
      supplementation is not justified for this hyporesponsiveness in patients with
      iron overload due to the potential hazards of iron overload aggravated by
      intravenous iron therapy. Furthermore, in vivo studies indicated that the
      promising effect of intravenous iron medication to overcome iron-deficient
      erythropoiesis is not observed in iron-overloaded haemodialysis (HD) patients.
      Ascorbic acid, a water-soluble antioxidant as well as a reducing agent, has a
      number of associations with iron metabolism. Recent research highlights that
      ascorbic acid can potentiate the mobilization of iron from inert tissue stores
      and facilitates the incorporation of iron into protoporphyrin in iron-overloaded
      HD patients being treated with rHuEpo. Interest has turned towards the use of
      ascorbic acid as an adjuvant therapy in this field. This review focuses on the
      improvement of rHuEpo response by administration of ascorbic acid and discusses
      its clinical implications and potential issues for nephrologists.

PMID- 11509683
TI  - Novel aspects of erythropoietin response in renal failure patients.
AB  - The invention of recombinant human erythropoietin (rHuEpo) for the treatment of
      renal anaemia was a hallmark in the care of patients with renal insufficiency.
      Recently published guidelines (European Best Practice Guidelines, NKF-DOQI) have
      set the target haemoglobin to be reached by treatment with rHuEpo to >11 g/dl.
      Normalizing haemoglobin levels may reduce morbidity and mortality and improve
      quality of life in haemodialysis patients. During long-term treatment, most
      patients will not respond adequately to therapy with rHuEpo alone. The most
      important confounding factor, limiting the effectiveness of rHuEpo, is absolute
      or functional iron deficiency, which is now recognized and treated in many
      dialysis units. However, there are several other adjuvant treatment options which
      may help to optimize the response to treatment with rHuEpo. A weekly dose of 2-3
      mg of folic acid and 100-150 mg of vitamin B6 is recommended for haemodialysis
      patients on rHuEpo therapy. The addition of 0.25 mg/month of vitamin B12 may be
      necessary in selected patients. Vitamin C (1-1.5 g/week) was shown to overcome
      functional iron deficiency in patients with high ferritin levels. The potential
      increase of oxidative stress induced by intravenous iron therapy may be blunted
      by concomitant administration of vitamin E (1200 IU). There is clear evidence
      from the literature that treatment of secondary hyperparathyroidism by vitamin D
      improves erythropoiesis. The most recently discovered biological effects of
      rHuEpo include the induction of several genes in endothelial cells as well as a
      role for erythropoietin in the outcome of plasmodium infection. A new
      erythropoietin-like molecule is novel erythropoiesis stimulating protein (NESP),
      which is as effective and safe as rHuEpo, with the potential advantage of less
      frequent dosing.

PMID- 11509684
TI  - The importance of early treatment of the anaemia of chronic kidney disease.
AB  - The beneficial effects of treating the anaemia of dialysis-dependent patients
      with erythropoietin on the improvement of cardiac status, exercise capacity,
      cognitive function and quality of life are well established. Equally, if not more
      important is the reduction in morbidity and mortality that accompanies the
      treatment of anaemia with epoietin. These documented improvements in outcomes of
      care notwithstanding, mortality and morbidity due to cardiovascular disease (CVD)
      remain high in dialysis patients. Recent epidemiological evidence indicates that:
      (i) the prevalence of CVD is very high in patients at the start of dialysis; (ii)
      pre-existing CVD is the major risk factor for mortality and morbidity on
      dialysis; (iii) CVD begins early in the course of kidney disease, shows an
      inverse relationship to kidney function and increases in prevalence and severity
      with progression of kidney disease; and (iv) corrective measures, which take 3-5
      years to show a favourable effect, must be instituted well before the initiation
      of dialysis. Hypertension and anaemia, which develop in the course of progressive
      reduction in kidney function, are the principal risk factors for the prevalence
      of left ventricular hypertrophy (LVH) in those with chronic kidney disease, and
      their treatment has been shown to arrest or reverse LVH in these individuals.
      Whereas the treatment of hypertension early in the course of kidney disease has
      been incorporated into clinical practice, there has been reluctance in the
      treatment of anaemia because of the possibility of worsening kidney function with
      epoietin, as shown in rats. There is now convincing evidence that epoietin has no
      potential adverse effect on kidney function in humans. While the most compelling
      reason for the early treatment of the anaemia of kidney disease is its beneficial
      effect on cardiovascular function, other documented potential benefits are
      improvements in exercise capacity, cognitive function and quality of life.

PMID- 11509685
TI  - Present and future strategies in the treatment of renal anaemia.
AB  - Recombinant human erythropoietin therapy has transformed the management of renal
      anaemia over the last decade or so. We have learned much about the optimum
      regimens for using this drug, including the route of administration, dosage
      frequency, use of iron supplementation, and management of poor response. Thus,
      dosage requirements of epoetin are generally lower if the drug is administered
      subcutaneously, and the most commonly used dosage frequency is two or three times
      weekly. The vast majority of patients respond very well to treatment, but
      approximately 5-10% of patients show some resistance to epoetin, the most common
      cause of which is iron deficiency. The presence of infection or inflammation and
      underdialysis are other important causes of a poor response to epoetin. There is
      increasing interest in treating renal anaemia at an earlier stage in the course
      of the disease, and there is much circumstantial evidence to support this
      strategy. This usually involves giving epoetin to pre-dialysis patients, and a
      study has also recently commenced to investigate the effects of preventing renal
      anaemia ever developing. Other erythropoietic substances are being developed, and
      the first of these to be ready for clinical use is novel erythropoiesis
      stimulating protein (NESP), which is an analogue of erythropoietin containing two
      extra N-linked carbohydrate side-chains. Other potential erythropoietic
      substances are still at the laboratory stage of development, but may be available
      for therapeutic use in the next decade or so.

PMID- 11509686
TI  - Determinants of haemodialyser performance and the potential effect on clinical
      outcome.
AB  - The performance of a dialyser is determined by several factors. Many of these
      factors relate to the dialyser membrane, including mean pore size, pore size
      distribution, wall thickness, surface area, and adsorptivity. In this article,
      several of these factors are reviewed. The potential impact of these factors on
      the clinical outcome of chronic haemodialysis patients is also discussed.

PMID- 11509687
TI  - Integrated end-stage renal disease care: the role of peritoneal dialysis.
AB  - This paper reviews the rationale behind the proposed policy of using peritoneal
      dialysis (PD) as the initial treatment modality in patients with end-stage renal
      disease (ESRD). The better preservation of residual renal function associated
      with PD is emphasized along with its potential cardiovascular benefits. The
      superior patient survival on PD, relative to hemodialysis, during the first 2
      years on dialysis in both the United States and Canada is discussed, as are the
      potential advantages of PD in terms of hepatitis C prevention, anaemia management
      and quality of life. The lower cost of PD in association with these clinical
      advantages lead to the modality being more cost-effective in the early years on
      dialysis. The relatively high technique failure rate on PD, however, subsequently
      leads to an increasing need for haemodialysis. A policy of integrated dialysis
      care with PD first and then haemodialysis, as required, is advocated as a more
      cost-effective approach to ESRD in suitable patients.

PMID- 11509688
TI  - Continuous renal replacement therapy in critically ill patients.
AB  - Acute renal failure is an evolving syndrome in which new pathogenetic mechanisms
      have recently been elucidated. The evolution of the field of haemodialysis has
      led to a parallel development in the therapeutic approach to patients suffering
      from this syndrome. In particular, acute renal failure is more frequently seen as
      part of a more complex syndrome, defined as multiple organ failure. In this
      clinical setting, patients are almost inevitably confined to intensive care units
      and sepsis is a frequent underlying mechanism of organ failure. The use of new
      devices and new machines, together with a better understanding of the underlying
      mechanisms of solute and water removal, have allowed us to achieve higher levels
      of efficiency and clinical tolerance during artificial renal replacement therapy.
      The first objective has been reached by increasing the automation of the
      extracorporeal circuits and the operational levels of the different techniques;
      the second has been achieved by means of a new generation of monitoring
      techniques and new machines equipped with specific interfaces and alarms. This
      progress has made continuous forms of renal replacement (CRRT) possible and easy
      to perform without major problems or complications. The most promising and
      effective options for treating acute renal failure in critically ill patients are
      today offered by continuous renal replacement therapies. Classic indications, but
      also alternative non-renal indications, have been proposed for these techniques.
      The most advanced indication is the multiple organ dysfunction occurring in
      septic patients. The possible removal of proinflammatory mediators may permit a
      blockade of the systemic inflammation, a modulation of the altered immune
      response in these patients, and it may lead to a partial or total restoration of
      the lost homeostasis.

PMID- 11509689
TI  - Leptospirosis renal disease.
AB  - Leptospirosis is a re-emerging infectious disease, affecting both animals and
      humans worldwide. Multiple organ involvement may be encountered in leptospirosis,
      and early renal involvement is very common, characterized by tubulo-interstitial
      nephritis and tubular dysfunction. All 12 patients diagnosed in Chang Gung
      Memorial Hospital (Taiwan) between 1997 and 1999 had acute renal failure, with
      five patients requiring dialysis. Leptospira shermani is the main serovar
      encountered in Taiwan, and penicillin may dramatically rescue patients from
      multiple organ failure provided it is given early. To understand the mechanism
      behind tubular injuries by leptospira infection, outer membrane proteins (OMPs)
      extracted from pathogenic leptospira were given to tubular cells in culture. Our
      in vitro experiment showed that OMPs of pathogenic leptospira activate nuclear
      NFkappaB binding and stimulate downstream inducible nitric oxide (iNOS), monocyte
      chemoattractant protein-1 (MCP-1) and tumor necrosis factor-alpha (TNF-alpha)
      expression. These results indicate that leptospiral infection may induce tubulo
      interstitial nephritis through a toxic component in the outer membrane followed
      by expression of inflammatory genes.

PMID- 11509690
TI  - Renal replacement therapy at the time of the Taiwan Chi-Chi earthquake.

PMID- 11509691
TI  - An essential role for BAFF in the normal development of B cells through a BCMA
      independent pathway.
AB  - The B cell activating factor BAFF (BlyS/TALL-1/zTNF4) is a tumor necrosis factor
      (TNF)-related ligand that promotes B cell survival and binds to three receptors
      (BCMA, TACI, and the recently described BAFF-R). Here we report an absolute
      requirement for BAFF in normal B cell development. Examination of secondary
      lymphoid organs from BAFF-deficient mice revealed an almost complete loss of
      follicular and marginal zone B lymphocytes. In contrast, mice lacking BCMA had
      normal-appearing B lymphocyte compartments. BAFF therefore plays a crucial role
      in B cell development and can function through receptors other than BCMA.

PMID- 11509692
TI  - BAFF-R, a newly identified TNF receptor that specifically interacts with BAFF.
AB  - B cell homeostasis has been shown to critically depend on BAFF, the B cell
      activation factor from the tumor necrosis factor (TNF) family. Although BAFF is
      already known to bind two receptors, BCMA and TACI, we have identified a third
      receptor for BAFF that we have termed BAFF-R. BAFF-R binding appears to be highly
      specific for BAFF, suggesting a unique role for this ligand-receptor interaction.
      Consistent with this, the BAFF-R locus is disrupted in A/WySnJ mice, which
      display a B cell phenotype qualitatively similar to that of the BAFF-deficient
      mice. Thus, BAFF-R appears to be the principal receptor for BAFF-mediated mature
      B cell survival.

PMID- 11509694
TI  - Going it alone.

PMID- 11509693
TI  - Direct interaction of Arabidopsis cryptochromes with COP1 in light control
      development.
AB  - Arabidopsis seedling photomorphogenesis involves two antagonistically acting
      components, COP1 and HY5. COP1 specifically targets HY5 for degradation via the
      26S proteasome in the dark through their direct physical interaction. Little is
      known regarding how light signals perceived by photoreceptors are transduced to
      regulate COP1. Arabidopsis has two related cryptochromes (cry1 and cry2)
      mediating various blue/ultraviolet-A light responses. Here we show that both
      photoactivated cryptochromes repress COP1 activity through a direct protein
      protein contact and that this direct regulation is primarily responsible for the
      cryptochrome-mediated blue light regulation of seedling photomorphogenic
      development and genome expression profile.

PMID- 11509695
TI  - Biomedical policy. NIH wins an exemption from HHS peer-review overhaul.

PMID- 11509696
TI  - Astronomy. Pull of gravity reveals unseen galaxy cluster.

PMID- 11509697
TI  - Advanced computing. NSF launches teragrid for academic research.

PMID- 11509699
TI  - Ecology. Field test backs model for invader.

PMID- 11509698
TI  - Plant science. How seedlings see the light.

PMID- 11509700
TI  - Human genome. Less can be more, U.K. study finds.

PMID- 11509701
TI  - Evolutionary biology. Queens, not workers, rule the ant nest.

PMID- 11509702
TI  - Ecology. Parasitic wasps invade Hawaiian ecosystem.

PMID- 11509703
TI  - Biomedical policy. Bush squeezes between the lines on stem cells.

PMID- 11509704
TI  - Biomedical policy. New chair of bioethics panel wants national debate on issues.

PMID- 11509705
TI  - Biomedical policy. "I have given this issue a great deal of thought ... and I
      have found widespread disagreement".

PMID- 11509706
TI  - Human evolution. Max Planck's meeting of the anthropological minds.

PMID- 11509707
TI  - Human evolution. Zoo's new primate exhibit to double as research lab.

PMID- 11509708
TI  - Science and commerce. Chemists for hire: have flask, will travel.

PMID- 11509709
TI  - Natural disasters. Researchers target deadly tsunamis.

PMID- 11509710
TI  - Natural disasters. Modeling a 3600-year-old tsunami sheds light on the Minoan
      past.

PMID- 11509711
TI  - Climate change. Hidden health benefits of greenhouse gas mitigation.

PMID- 11509712
TI  - Cell biology. A switch to release the motor.

PMID- 11509713
TI  - Enzymology. Nickel to the fore.

PMID- 11509714
TI  - Laser physics. Getting to grips with light.

PMID- 11509715
TI  - Ecology and conservation. Whose fish are they anyway?

PMID- 11509716
TI  - Oceanography. Patterns of Arctic circulation.

PMID- 11509717
TI  - Biochemistry. TRP ion channels--two proteins in one.

PMID- 11509718
TI  - Neurobiology. Learning how a fruit fly forgets.

PMID- 11509719
TI  - The morphological evolution of galaxies.
AB  - Many galaxies have taken on their familiar appearance relatively recently. In the
      distant Universe, galaxy morphology deviates significantly (and systematically)
      from that of nearby galaxies at redshifts (z) as low as 0.3. This corresponds to
      a time approximately 3.5 x 10(9) years in the past, which is only approximately
      25% of the present age of the Universe. Beyond z = 0.5 (5 x 10(9) years in the
      past), spiral arms are less well developed and more chaotic, and barred spiral
      galaxies may become rarer. At z = 1, around 30% of the galaxy population is
      sufficiently peculiar that classification on Hubble's traditional "tuning fork"
      system is meaningless. On the other hand, some characteristics of galaxies have
      not changed much over time. The space density of luminous disk galaxies has not
      changed significantly since z = 1, indicating that although the general
      appearance of these galaxies has continuously changed over time, their overall
      numbers have been conserved.

PMID- 11509720
TI  - Crystal structure of a carbon monoxide dehydrogenase reveals a [Ni-4Fe-5S]
      cluster.
AB  - The homodimeric nickel-containing CO dehydrogenase from the anaerobic bacterium
      Carboxydothermus hydrogenoformans catalyzes the oxidation of CO to CO2. A crystal
      structure of the reduced enzyme has been solved at 1.6 angstrom resolution. This
      structure represents the prototype for Ni-containing CO dehydrogenases from
      anaerobic bacteria and archaea. It contains five metal clusters of which clusters
      B, B', and a subunit-bridging, surface-exposed cluster D are cubane-type [4Fe-4S]
      clusters. The active-site clusters C and C' are novel, asymmetric [Ni-4Fe-5S]
      clusters. Their integral Ni ion, which is the likely site of CO oxidation, is
      coordinated by four sulfur ligands with square planar geometry.

PMID- 11509721
TI  - Phase-coherent optical pulse synthesis from separate femtosecond lasers.
AB  - We generated a coherently synthesized optical pulse from two independent mode
      locked femtosecond lasers, providing a route to extend the coherent bandwidth
      available for ultrafast science. The two separate lasers (one centered at 760
      nanometers wavelength, the other at 810 nanometers) are tightly synchronized and
      phase-locked. Coherence between the two lasers is demonstrated via spectral
      interferometry and second-order field cross-correlation. Measurements reveal a
      coherently synthesized pulse that has a temporally narrower second-order
      autocorrelation width and that exhibits a larger amplitude than the individual
      laser outputs. This work represents a new and flexible approach to the synthesis
      of coherent light.

PMID- 11509722
TI  - Nanowire nanosensors for highly sensitive and selective detection of biological
      and chemical species.
AB  - Boron-doped silicon nanowires (SiNWs) were used to create highly sensitive, real
      time electrically based sensors for biological and chemical species. Amine- and
      oxide-functionalized SiNWs exhibit pH-dependent conductance that was linear over
      a large dynamic range and could be understood in terms of the change in surface
      charge during protonation and deprotonation. Biotin-modified SiNWs were used to
      detect streptavidin down to at least a picomolar concentration range. In
      addition, antigen-functionalized SiNWs show reversible antibody binding and
      concentration-dependent detection in real time. Lastly, detection of the
      reversible binding of the metabolic indicator Ca2+ was demonstrated. The small
      size and capability of these semiconductor nanowires for sensitive, label-free,
      real-time detection of a wide range of chemical and biological species could be
      exploited in array-based screening and in vivo diagnostics.

PMID- 11509723
TI  - Stable ordering in Langmuir-Blodgett films.
AB  - Defects in the layering of Langmuir-Blodgett (LB) films can be eliminated by
      depositing from the appropriate monolayer phase at the air-water interface. LB
      films deposited from the hexagonal phase of cadmium arachidate (CdA2) at pH 7
      spontaneously transform into the bulk soap structure, a centrosymmetric bilayer
      with an orthorhombic herringbone packing. A large wavelength folding mechanism
      accelerates the conversion between the two structures, leading to a disruption of
      the desired layering. At pH > 8.5, though it is more difficult to draw LB films,
      almost perfect layering is obtained due to the inability to convert from the as
      deposited structure to the equilibrium one.

PMID- 11509724
TI  - Principles for measurement of chemical exposure based on recognition-driven
      anchoring transitions in liquid crystals.
AB  - The competitive binding of a molecule forming a liquid crystal and a targeted
      analyte to a common molecular receptor presented at a solid surface possessing
      nanometer-scale topography is used to trigger an easily visualized surface-driven
      change in the orientation of a micrometer-thick film of liquid crystal. Diffusion
      of the targeted analyte from atmosphere to surface-immobilized receptor across
      the micrometer-thick film of liquid crystal is fast (on the order of seconds),
      and the competitive interaction of the targeted analyte and liquid crystal with
      the receptor provides a high level of tolerance to nontargeted species (water,
      ethanol, acetone, and hexanes). Systems that provide parts-per-billion (by
      volume) sensitivity to either organoamine or organophosphorus compounds are
      demonstrated, and their use for imaging of spatial gradients in concentration is
      reported. This approach does not require complex instrumentation and could
      provide the basis of wearable personalized sensors for measurement of real-time
      and cumulative exposure to environmental agents.

PMID- 11509725
TI  - Ring closure of carbon nanotubes.
AB  - Lightly etched single-walled carbon nanotubes are chemically reacted to form
      rings. The rings appear to be fully closed as opposed to open coils, as ring
      opening reactions did not change the structure of the observed rings. The average
      diameter of the rings was 540 nanometers with a narrow size distribution. The
      nanotubes in solution were modeled as wormlike polymer chains, yielding a
      persistence length of 800 nanometers. Nanotubes shorter than this length behave
      stiffly and stay nearly straight in solution. However, nanotubes longer than the
      Kuhn segment length of 1600 nanometers undergo considerable thermal fluctuation,
      suggesting a greater flexibility of these materials than is generally assumed.

PMID- 11509726
TI  - Atlantic water flow pathways revealed by lead contamination in Arctic basin
      sediments.
AB  - Contaminant lead in sediments underlying boundary currents in the Arctic Ocean
      provides an image of current organization and stability during the past 50 years.
      The sediment distributions of lead, stable lead isotope ratios, and lead-210 in
      the major Arctic Ocean basins reveal close coupling of the Eurasian Basin with
      the North Atlantic during the 20th century. They indicate that the Atlantic water
      boundary current in the Eurasian Basin has been a prominent pathway, that
      contaminant lead from the Laptev Sea supplies surface water in the transpolar
      drift, and that the Canadian and Eurasian basins have been historically
      decoupled.

PMID- 11509727
TI  - Southward migration of the intertropical convergence zone through the Holocene.
AB  - Titanium and iron concentration data from the anoxic Cariaco Basin, off the
      Venezuelan coast, can be used to infer variations in the hydrological cycle over
      northern South America during the past 14,000 years with subdecadal resolution.
      Following a dry Younger Dryas, a period of increased precipitation and riverine
      discharge occurred during the Holocene "thermal maximum." Since approximately
      5400 years ago, a trend toward drier conditions is evident from the data, with
      high-amplitude fluctuations and precipitation minima during the time interval
      3800 to 2800 years ago and during the "Little Ice Age." These regional changes in
      precipitation are best explained by shifts in the mean latitude of the Atlantic
      Intertropical Convergence Zone (ITCZ), potentially driven by Pacific-based
      climate variability. The Cariaco Basin record exhibits strong correlations with
      climate records from distant regions, including the high-latitude Northern
      Hemisphere, providing evidence for global teleconnections among regional
      climates.

PMID- 11509728
TI  - Queen control of sex ratio in fire ants.
AB  - The haplodiploid sex-determination system of ants gives rise to conflict between
      queens and workers over colony sex ratios, and the female-biased allocation
      ratios seen in many species suggest that workers often prevail in this conflict.
      We exchanged queens between male- and female-specialist colonies of the fire ant
      Solenopsis invicta. These exchanges quickly reversed the sex-ratio biases of
      adopting colonies. The sex ratio of queen-laid eggs differed strongly between
      male- and female-specialist colonies. These findings suggest that queens can
      force workers to raise male sexuals by limiting the number of female brood and
      help to explain why sex investment ratios lie between the queen and worker
      equilibria in this and many other ant species.

PMID- 11509729
TI  - Migratory movements, depth preferences, and thermal biology of Atlantic bluefin
      tuna.
AB  - The deployment of electronic data storage tags that are surgically implanted or
      satellite-linked provides marine researchers with new ways to examine the
      movements, environmental preferences, and physiology of pelagic vertebrates. We
      report the results obtained from tagging of Atlantic bluefin tuna with
      implantable archival and pop-up satellite archival tags. The electronic tagging
      data provide insights into the seasonal movements and environmental preferences
      of this species. Bluefin tuna dive to depths of >1000 meters and maintain a warm
      body temperature. Western-tagged bluefin tuna make trans-Atlantic migrations and
      they frequent spawning grounds in the Gulf of Mexico and eastern Mediterranean.
      These data are critical for the future management and conservation of bluefin
      tuna in the Atlantic.

PMID- 11509730
TI  - Infiltration of a Hawaiian community by introduced biological control agents.
AB  - To examine the community-wide effects of introduced biocontrol agents on Kauai
      Island, Hawaii, we constructed quantitative food webs showing interactions among
      plants, moths, and moth parasitoids in a native forest. Eighty-three percent of
      parasitoids reared from native moths were biological control agents, 14% were
      accidental immigrants, and 3% were native species. Although parasitism by
      biological control agents reached 28% in some species of moth, all biocontrol
      agents reared had been released before 1945. This study highlights the importance
      of considering the potential damage caused by an introduced control agent, in
      addition to that caused by the target alien species.

PMID- 11509731
TI  - Cell cycle regulation of myosin-V by calcium/calmodulin-dependent protein kinase
      II.
AB  - Organelle transport by myosin-V is down-regulated during mitosis, presumably by
      myosin-V phosphorylation. We used mass spectrometry phosphopeptide mapping to
      show that the tail of myosin-V was phosphorylated in mitotic Xenopus egg extract
      on a single serine residue localized in the carboxyl-terminal organelle-binding
      domain. Phosphorylation resulted in the release of the motor from the organelle.
      The phosphorylation site matched the consensus sequence of calcium/calmodulin
      dependent protein kinase II (CaMKII), and inhibitors of CaMKII prevented myosin-V
      release. The modulation of cargo binding by phosphorylation is likely to
      represent a general mechanism regulating organelle transport by myosin-V.

PMID- 11509732
TI  - Cohesin cleavage by separase required for anaphase and cytokinesis in human
      cells.
AB  - Cell division depends on the separation of sister chromatids in anaphase. In
      yeast, sister separation is initiated by cleavage of cohesin by the protease
      separase. In vertebrates, most cohesin is removed from chromosome arms by a
      cleavage-independent mechanism. Only residual amounts of cohesin are cleaved at
      the onset of anaphase, coinciding with its disappearance from centromeres. We
      have identified two separase cleavage sites in the human cohesin subunit SCC1 and
      have conditionally expressed noncleavable SCC1 mutants in human cells. Our
      results indicate that cohesin cleavage by separase is essential for sister
      chromatid separation and for the completion of cytokinesis.

PMID- 11509733
TI  - Vascular abnormalities and deregulation of VEGF in Lkb1-deficient mice.
AB  - The LKB1 tumor suppressor gene, mutated in Peutz-Jeghers syndrome, encodes a
      serine/threonine kinase of unknown function. Here we show that mice with a
      targeted disruption of Lkb1 die at midgestation, with the embryos showing neural
      tube defects, mesenchymal cell death, and vascular abnormalities. Extraembryonic
      development was also severely affected; the mutant placentas exhibited defective
      labyrinth layer development and the fetal vessels failed to invade the placenta.
      These phenotypes were associated with tissue-specific deregulation of vascular
      endothelial growth factor (VEGF) expression, including a marked increase in the
      amount of VEGF messenger RNA. Moreover, VEGF production in cultured Lkb1(-/-)
      fibroblasts was elevated in both normoxic and hypoxic conditions. These findings
      place Lkb1 in the VEGF signaling pathway and suggest that the vascular defects
      accompanying Lkb1 loss are mediated at least in part by VEGF.

PMID- 11509735
TI  - Tech.Sight. Color by number: imaging large data.

PMID- 11509734
TI  - Immunocyte Ca2+ influx system mediated by LTRPC2.
AB  - We characterized an activation mechanism of the human LTRPC2 protein, a member of
      the transient receptor potential family of ion channels, and demonstrated that
      LTRPC2 mediates Ca2+ influx into immunocytes. Intracellular pyrimidine
      nucleotides, adenosine 5'-diphosphoribose (ADPR), and nicotinamide adenine
      dinucleotide (NAD), directly activated LTRPC2, which functioned as a Ca2+
      permeable nonselective cation channel and enabled Ca2+ influx into cells. This
      activation was suppressed by intracellular adenosine triphosphate. These results
      reveal that ADPR and NAD act as intracellular messengers and may have an
      important role in Ca2+ influx by activating LTRPC2 in immunocytes.

PMID- 11509737
TI  - The early days of SOT. Society of Toxicology.

PMID- 11509736
TI  - Biologically motivated quantitative models and the mixture toxicity problem.
AB  - The article highlighted in this issue is "A PBPK Modeling-Based Approach to
      Account for Interactions in the Health Risk Assessment of Chemical Mixtures" by
      Sami Haddad, Martin Beliveau, Robert Tardif, and Kannan Krishnan (pp. 125-131).

PMID- 11509738
TI  - TestSmart-high production volume chemicals: an approach to implementing
      alternatives into regulatory toxicology.
AB  - This article examines the status and application of alternatives defined as
      replacements, refinements, and reduction for screening high production volume
      (HPV) chemicals. It specifically focuses on the Screening Information Data Set
      (SIDS), a series of toxicological tests recommended by the Organization for
      Economic Cooperation and Development to screen such chemicals. Alternative tests
      associated with acute, repeat-dose, genetic, and reproductive and developmental
      toxicity were examined at 2 meetings of academic, industry, and regulatory
      scientists and their status determined. Tests were placed in 1 of 3 categories:
      ready for immediate use, in need of or currently undergoing validation, or
      needing research/developmental work. With respect to traditional acute toxicity
      testing, the basal cytotoxicity approach was placed in the category of research
      with the up-and-down, fixed-dose, limit test, and the acute toxic class
      categorized as available for immediate use and the neutral red assay under
      validation. Cell culture methods that could provide information on acute target
      organ toxicity were all categorized in the research stage. Studies of the Ah
      receptor were placed under validation. All alternative tests for repeat-dose
      toxicity were placed in the category of research. With regard to genetic
      toxicity, the Ames, mouse lymphoma, and Chinese hamster ovary methods were
      considered ready for immediate use, while the in vitro micronucleus and Syrian
      hamster ovary assays were placed in the validation category. All alternatives for
      developmental toxicity, with the exception of gene chip technology, were placed
      in the category of validation. Gene chip technology is considered to be in the
      research stage. For reproductive toxicity, sperm motility and morphology were
      considered as ready for immediate use, with the other assays categorized as
      needing validation or in the research stage. Follow-up to these results is
      obvious. Work needs to be conducted to move those tests from the research stage
      to the validation and use stage. This is one approach to the development of
      alternatives to SIDS. Progress along these lines would apply not only to SIDS but
      also to toxicology in general.

PMID- 11509739
TI  - Induction of hepatic microsomal drug-metabolizing enzymes by inhibitors of 5
      lipoxygenase (5-LO): studies in rats and 5-LO knockout mice.
AB  - The effect of 5-lipoxygenase (5-LO) inhibitors on the hepatic microsomal mixed
      function oxidase (MFO) system of rodents was investigated. After establishing the
      relative in vitro and in vivo potencies of the 3 test compounds, male Crl:CD (SD)
      BR rats received CJ-11,802 (0, 10, 50, or 200 mg/kg/day), zileuton (0, 10, 60, or
      300 mg/kg/day) or ZD2138 (0 or 200 mg/kg/day) once daily by oral gavage for 14
      (zileuton and ZD2138) or 30 (CJ-11,802) consecutive days. Controls were given an
      equivalent volume of 0.5% methylcellulose vehicle. At necropsy, all livers were
      weighed, and sections from representative animals (control and highest dose for
      each compound) were utilized to prepare hepatic microsomal fractions, which were
      assayed for cytochrome P-450 (CYP) content and the activities of cytochrome c
      reductase (CRed), para-nitroanisole O-demethylase (p-NOD), ethoxyresorufin O
      deethylase (EROD), and pentoxyresorufin O-dealkylase (PROD). A dose-related
      increase in liver weight occurred in rats given CJ-11,802 and zileuton, while
      animals administered ZD2138 were unaffected. Rats given CJ-11,802 (200 mg/kg/day)
      and zileuton (300 mg/kg/day) had increases in CYP, EROD, PROD, CRed and p-NOD
      compared to corresponding controls, while only the latter two activities were
      elevated in animals administered ZD2138. To determine if induction of the hepatic
      microsomal MFO system was related to 5-LO inhibition, male DBA wild-type and 5-LO
      knockout mice were administered either CJ-11,802 (200 mg/kg/day) or vehicle by
      oral gavage for 14 consecutive days. At necropsy, liver weight, CYP content, and
      CRed activity were measured and all were increased similarly in the treated wild
      type and knockout mice compared to corresponding controls, indicating that
      induction was not related to inhibiting 5-LO.

PMID- 11509740
TI  - Physiologically based pharmacokinetic model for tetrachlorobenzyltoluenes in rat:
      comparison of in vitro and in vivo metabolic rates.
AB  - Ugilec 141 is a technical mixture of tetrachlorobenzyltoluenes (TCBTs). It was
      introduced in the early 1980s as a replacement for polychlorinated biphenyls
      (PCBs). Based on physicochemical properties and accumulation in the environment,
      the use of this mixture was prohibited. To gain more insight in the
      toxicokinetics of these compounds in mammals, rats were exposed to a single iv
      bolus injection of a mixture of 3 TCBTs. At different time points after dosing,
      the tissue and blood concentrations of the TCBTs were determined. The adipose
      tissue is the main storage compartment, followed by skin and muscle. The TCBTs
      were rapidly eliminated from the liver and the blood, with half lives ranging
      from 65 to 72 h. Additionally, the tissue concentration data for all 3 TCBTs were
      analyzed using a physiologically based pharmacokinetic (PB-PK) model. Sensitivity
      analysis illustrated that the elimination of the TCBTs was not influenced by
      metabolism only, but also by the blood flow through the liver. Furthermore, the
      metabolic rates derived from the model were compared to previously reported in
      vitro metabolic rates. The in vitro values for the TCBTs were only a factor 2 to
      3 smaller than the in vivo metabolic rates, indicating the value of in vitro
      techniques for a priori parameterization of PB-PK models.

PMID- 11509741
TI  - Effect of phosphate transporter and methylation inhibitor drugs on the
      disposition of arsenate and arsenite in rats.
AB  - Arsenate (AsV) is biotransformed into the more toxic arsenite (AsIII) and
      monomethylarsonous acid (MMAsIII), but it is unknown how to decrease production
      of these harmful metabolites. We investigated the effects of foscarnet and
      fosfomycin, drugs interacting with the phosphate transporter, on
      biotransformation of AsV, an analog of inorganic phosphate. The effects of
      entacapone, an inhibitor of catechol-O-methyl transferase (COMT), and nitrous
      oxide, an inactivator of methylcobalamin, were also tested on the formation of
      MMAsIII from AsIII in order to clarify the role of COMT and methylcobalamin in
      biomethylation of AsIII. Arsenic in bile and urine of control and treated rats
      receiving AsV or AsIII was speciated by HPLC-HG-AFS. In AsV-injected rats,
      foscarnet, but not fosfomycin, increased the urinary excretion of AsV and
      decreased the biliary and urinary excretion of AsIII as well as biliary excretion
      of MMAsIII. In AsIII-injected rats, however, foscarnet failed to influence the
      excretion of AsIII and its metabolites, suggesting that this drug inhibits the
      hepatic uptake and renal reabsorption of AsV, thereby decreasing formation of
      AsIII and MMAsIII from AsV. Entacapone or nitrous oxide pretreatment slightly or
      not at all influenced the biliary excretion of MMAsIII and urinary excretion of
      dimethylarsinic acid (DMAsV) in AsIII-injected rats. In contrast, periodate
      oxidized adenosine, an inhibitor of S-adenosylmethionine-dependent
      methyltransferases, nearly abolished appearance of methylated arsenic metabolites
      in bile and urine. Thus, foscarnet facilitates urinary clearance of AsV and
      decreases formation of toxic AsIII and MMAsIII, indicating that this drug may be
      used to promote elimination and counter toxification of AsV. Because entacapone
      and nitrous oxide influenced the excretion of MMAsIII and DMAsV negligibly,
      neither COMT nor methylcobalamin appears to be involved in arsenic methylation in
      rats.

PMID- 11509742
TI  - Potential estrogenic and antiestrogenic activity of the cyclic siloxane
      octamethylcyclotetrasiloxane (D4) and the linear siloxane hexamethyldisiloxane
      (HMDS) in immature rats using the uterotrophic assay.
AB  - The cyclic siloxane octamethylcyclotetrasiloxane (D4) and the linear siloxane
      hexamethyldisiloxane (HMDS) have numerous industrial and consumer applications
      and thus have the potential for human exposure. The present study was undertaken
      to examine potential estrogenic and antiestrogenic activities of D4 and HMDS. To
      address potential differences in sensitivity between rat strains the study used
      both Sprague-Dawley (SD) and Fischer 344 (F-344) rats. Estrogenicity of the test
      compounds was determined by measuring absolute and relative uterine weights in
      immature rats and by monitoring uterine epithelial cell height. In order to place
      the data obtained for D4 into perspective relative to strong and weak estrogenic
      compounds, the response produced by D4 at 0, 10, 50, 100, 250, 500, and 1000
      mg/kg/day was compared to responses produced by ethinyl estradiol (EE) (1, 3, 10,
      or 30 microg/kg/day), diethylstilbestrol dipropionate (DES-DP) (0.5, 1.5, 5, 15
      microg/kg/day), and coumestrol (CE) (10, 35, 75, 150 mg/kg/day). Antiestrogenic
      effects were evaluated by co-administering D4 (500 mg/kg/day) with EE at 1, 3,
      10, and 30 microg /kg/day. All compounds were administered in sesame oil at a
      volume of 5 mL/kg by oral gavage. Beginning on postnatal day 18 (SD) or 21 (F
      344) each pup (12 per group) received a single dose of test compound once a day
      for 4 consecutive days. The pups were euthanized the morning after the last
      treatment and their uteri removed, weighed, and processed for histological
      examination. EE and DES-DP produced a significant dose-dependent increase in
      absolute and relative uterine weights and uterine cell height. The maximum
      increase in uterine weight following EE exposure was approximately 350% relative
      to controls in both strains. The weak phytoestrogen CE also produced a dose
      related increase in absolute and relative uterine weight and epithelial cell
      height, but the response occurred over a much higher range of doses. At the
      highest dose of CE, uterine weight was increased approximately 230% relative to
      controls. Following exposure to D4, absolute and relative uterine weights and
      uterine epithelial cell height were statistically significantly increased in both
      strains of rats at doses above 100 mg/kg/day. In terms of uterine weight, D4 was
      approximately 0.6 million times less potent than EE or DES-DP in SD pups and 3.8
      million times less potent than EE or DES-DP in F-344 pups. The maximal increase
      in uterine weight, relative to controls, produced by D4 at 1000 mg/kg/day was
      approximately 160% in SD rats, while the maximum increase produced by D4 in F-344
      rats was 86%. D4 co-administered over a wide range of EE doses, resulted in a
      significant reduction in uterine weight compared to EE alone. HMDS was evaluated
      in SD rats only. The response produced by HMDS (600 and 1200 mg/kg/day) was
      compared to EE (3 microg/kg/day). Antiestrogenic effects were evaluated by co
      administering HMDS (1200 mg/kg/day) with EE at 3 microg/kg/day. HMDS had no
      measurable effect on uterine weight under the experimental conditions described
      here. However, HMDS coadministered with EE did produce a small, but statistically
      significant reduction in uterine weight compared to EE alone. In conclusion, D4
      showed weak estrogenic and antiestrogenic activity that was several orders of
      magnitude less potent than EE, and many times less potent than the weak
      phytoestrogen CE.

PMID- 11509744
TI  - Mechanisms for the cytotoxicity of cysteamine.
AB  - The major aim of this study was to quantitatively assess the contribution of H2O2
      generation to the cytotoxicity induced by cysteamine. Cysteamine produces H2O2 at
      levels that correlate with its toxicity between 23 and 160 microM. A maximum of
      6.9 microM H2O2 is generated by 625 microM cysteamine. When compared to the
      toxicity of exogenous H2O2, cysteamine-derived peroxide accounted for 57% of its
      toxicity. This corresponded to the percent toxicity due to 23 to 91 microM
      cysteamine. The remaining 43% toxicity appears to involve the inhibition of
      glutathione peroxidase, because activity of both the cellular and purified enzyme
      were inhibited by 200 microM cysteamine concentrations. CCRF-CEM cells have no
      catalase activity, so the inhibition of glutathione peroxidase may sensitize
      these cells to the less than toxic levels of peroxide generated by this
      aminothiol. Cysteamine also stimulated the production of cellular glutathione in
      a manner that was not related to its H2O2 generation. The production of
      glutathione did not influence toxicity but may reflect the accumulation of
      cysteamine to levels that inhibit glutathione peroxidase.

PMID- 11509743
TI  - Differential gene expression in response to methoxychlor and estradiol through
      ERalpha, ERbeta, and AR in reproductive tissues of female mice.
AB  - The reproductive and developmental effects of 17beta-estradiol (E2) and
      methoxychlor (MXC) observed in treated rodents appear to be linked to some unique
      but also overlapping patterns of gene expression. The MXC metabolite 2,2-bis(p
      hydroxyphenyl)-1,1,1-trichloroethane (HPTE) was previously shown to have
      selective agonist activity through estrogen receptor alpha (ERalpha) and
      antagonist activity through ERbeta and androgen receptor (AR). To discover gene
      families regulated by HPTE and E2, and to characterize similarities and
      differences in patterns of gene expression induced by these selective ER ligands,
      we analyzed tissues from mice treated for 3 days with a combined treatment of E2
      and HPTE (E2 + HPTE), or the antiandrogen flutamide (FLU). RNA from uteri and
      ovaries was analyzed with cDNA microarrays and real-time RT-PCR. Results indicate
      that HPTE and E2 acted similarly to regulate most gene families in the uterus,
      which expresses predominantly ERalpha. However, in both the uterus and the ovary,
      there were a few genes that displayed differential patterns of gene regulation by
      E2 or HPTE treatment, presumably through ERbeta, AR, or other unidentified
      pathways. In the uterus, progesterone receptor, ERalpha, AR, insulin-like growth
      factor 1, insulin-like growth factor binding protein 5, and clusterin mRNAs were
      significantly reduced with both E2 or HPTE treatments, whereas cathepsin B was
      induced. Conversely, in the ovary, induction of cathepsin B by E2 was reversed
      after cotreatment with HPTE, and ERbeta expression was induced similarly by HPTE
      and FLU but not by E2. In addition, E2 uniquely regulated glutathione peroxidase
      3, glutathione S-transferase, and cytochrome P450 17alpha-hydroxylase, with no
      effect of HPTE or FLU treatments. This analysis demonstrated several gene
      families that appear to be regulated in a ligand-specific pattern, which may
      explain the unique but overlapping reproductive tissue pathologies following
      exposure to E2 and MXC.

PMID- 11509745
TI  - Inducing effects of dioxin-like polychlorinated biphenyls on CYP1A in the human
      hepatoblastoma cell line HepG2, the rat hepatoma cell line H4IIE, and rat primary
      hepatocytes: comparison of relative potencies.
AB  - Polychlorinated biphenyls (PCBs) are a group of widespread environmental
      pollutants. Some non-ortho-substituted congeners with a high likelihood of
      coplanarity of both aromatic rings have been shown to act like 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD) as agonists of the aryl hydrocarbon receptor
      (AhR) subsequently leading to adverse effects, such as immunosuppression and
      tumor promotion. Although there is a broad base of experimental data concerning
      the toxicity of PCBs in laboratory animals and animal-derived primary cells and
      cell lines, only few experimental data are available for cells of human origin.
      As a parameter of AhR activation, induction of CYP1A-mediated 7-ethoxyresorufin O
      deethylase (EROD) activity was determined in the human hepatoblastoma cell line
      HepG2 treated with the PCBs IUPAC Nos. 77, 81, 105, 114, 118, 123, 126, 156, 157,
      167, 169, and 189, and with TCDD as a positive control. Compared with results in
      rat primary hepatocytes and the rat hepatoma cell line H4IIE, treated HepG2 cells
      showed lower specific EROD activities maximally inducible by TCDD and PCBs, and
      EC50 values were shifted to higher concentrations. Furthermore, relative potency
      factors (REPs) for some congeners such as PCBs 81, 126, and 169 greatly differed
      from those observed in cells derived from rats. Northern blot analyses showed
      that EROD activities run parallel to changes in CYP1A-specific mRNA contents. The
      considerable differences in EROD-derived REPs between cells of human and rat
      origin indicate the need for further investigations in experimental models from
      different species including humans in order to extend the database of biochemical
      and toxic responses to PCBs.

PMID- 11509746
TI  - Methylmercury-induced decrement in neuronal migration may involve cytokine
      dependent mechanisms: a novel method to assess neuronal movement in vitro.
AB  - A major toxic effect associated with methylmercury (MeHg) exposure in developing
      humans is damage to the nervous system, which involves inhibition of cell
      migration, particularly in the cerebellum. The mechanisms by which MeHg impairs
      neural migration are not fully known, especially at low doses. In this paper we
      report on a novel method for observing and quantitating the movement of
      individual cells in primary cultures of murine neonatal cerebellar cells, which
      offers an opportunity to assess the role of endogenous and exogenous factors on
      neural migration. We have used this system to test the hypothesis that treatment
      with methylmercury would inhibit movement of granule cell neurons, possibly via a
      cytokine-mediated mechanism. We demonstrate that LPS (50 ng/ml) increases
      movement of neurons, concomitant with increased levels of TNF-alpha and IL-6
      secreted protein, and IL-1alpha mRNA. Treatment with LPS did not increase the
      number of neurons that moved, but, of the cells that did move, exposure to LPS
      significantly increased the total distances moved. Treatment with methylmercury
      (0.1 microM) decreased the number of moving cells and inhibited overall distance
      traveled by granule cells.

PMID- 11509747
TI  - Embryonic subcellular distribution of 13-cis- and all-trans-retinoic acid
      indicates differential cytosolic/nuclear localization.
AB  - Isotretinoin (13-cis-retinoic acid [13CRA], Accutane) is used for the treatment
      of dermatological diseases. Isotretinoin is, however, teratogenic in animals and
      humans. The mechanism of action of its teratogenicity is still not clearly
      identified. It has little or no binding properties to cytosolic retinoid-binding
      proteins or nuclear retinoid receptors (RAR, RXR). One hypothesis is that the
      teratogenicity of 2 approximately equipotent teratogenic doses of 13CRA and all
      trans-retinoic acids (ATRA) could mainly be correlated to ATRA in the nuclei,
      where the retinoic acid receptors (RARs) are located. To test this hypothesis,
      female mice at gestational day 11 were treated with approximately equipotent
      teratogenic doses of 13-cis-retinoic acid (100 mg/kg orally) or all-trans
      retinoic acid (10 mg/kg orally) and sacrificed 1 h and 4 h after administration.
      Embryos were homogenized and centrifuged into 4 fractions, and the purity of the
      fractions was tested by quantification of marker constituents for various cell
      compartments. We analyzed, by RP-HPLC, nuclear, mitochondrial, microsomal, and
      cytosolic fractions, as well as embryo homogenate and maternal plasma. After
      treatment with 13-cis-retinoic acid, this substance was mainly located in the
      nuclear fraction of the embryo (approximately 82%), whereas all-trans-retinoic
      acid, after ATRA treatment, was mainly located in the cytosolic supernatant
      (approximately 64%). The binding to cellular retinoid-binding protein (CRABP) may
      limit the access of ATRA to the nucleus, in contrast to 13CRA, which does not
      bind to CRABP. The concentration of ATRA in the nuclear fraction was similar
      after administration of either 13CRA or ATRA. The teratogenic activity of 13-cis
      retinoic acid could therefore be explained by its access to the nucleus and its
      possible conversion to all-trans-retinoic acids, which will interact with the
      nuclear retinoid receptors.

PMID- 11509748
TI  - Inflammatory effects of respirable quartz collected in workplaces versus standard
      DQ12 quartz: particle surface correlates.
AB  - In 1997, the IARC (International Agency for Research on Cancer) reevaluated its
      quartz classification from a class 2 carcinogen, to that of a class 1, stating
      sufficient evidence for carcinogenicity in both humans and experimental animals.
      However, tumor development did not occur across all occupational settings. It is
      probable that this is due to the considerable differences in toxicity between
      workplace quartz in comparison to quartz used in experimental studies. We
      therefore hypothesized that workplace quartz samples differ in toxicity from
      standard experimental quartz samples at equal mass. To test this hypothesis we
      compared 2 workplace quartz samples (RH1 and OM) with standard experimental
      quartz (DQ12) in several assays commonly used in particle toxicology. The sizes
      of the quartz samples were as closely matched as possible. The endpoints of this
      study were inflammation in the rat lung following intratracheal instillation
      (1000 microg or 250 microg for 3 or 14 days), release of soluble iron,
      cytotoxicity to cells in culture, and surface reactivity as assessed by hemolysis
      and ESR. The workplace samples did not cause inflammation at any dose or time
      point. DQ12 quartz caused marked inflammatory responses, as measured by an
      increased number of neutrophils in the lungs of instilled animals for both time
      points and doses. Protein in the bronchoalveolar lavage also increased in animals
      exposed to DQ12 but not the workplace samples. In vitro, DQ12 had the greatest
      hemolytic activity but only RH1 released substantial amounts of soluble iron. The
      increased inflammogenicity of DQ12 was not wholly explained by a greater surface
      area, by diameter, or by releasable iron. The hemolytic activity of DQ12, while
      not being informative in terms of understanding the mechanism of carcinogenicity,
      was the best in vitro predictor for in vivo activity. Therefore the surface
      reactivity of DQ12 appears to drive its inflammogenicity.

PMID- 11509749
TI  - Lung fibrosis in Sprague-Dawley rats, induced by exposure to manual metal arc
      stainless steel welding fumes.
AB  - To investigate the disease process of pneumoconiosis induced by welding-fume
      exposure, a lung fibrosis model was established by building a stainless steel arc
      welding fume generation system and exposing male Sprague-Dawley rats for 90 days.
      The rats were exposed to welding fumes with concentrations of 57-67 mg/m3 (low
      dose) and 105-118 mg/m3 (high dose) total suspended particulates for 2 h per day
      in an inhalation chamber for 90 days. The concentrations of the main metals, Fe,
      Mn, Cr, and Ni, were measured in the welding fumes, plus the gaseous compounds,
      including nitrous gases and ozone, were monitored. During the exposure period,
      the animals were sacrificed after the initial 2-h exposure and after 15, 30, 60,
      and 90 days. Histopathological examinations were conducted on the animals' upper
      respiratory tract, including the nasal pathway and conducting airway, plus the
      gas exchange region, including the alveolar ducts, alveolar sacs, and alveoli.
      When compared to the control group, the lung weights did not increase
      significantly in the low-dose group, yet in the high-dose group there was a
      significant increase from day 15 to day 90. The histopathological examination
      combined with fibrosis-specific staining (Masson's trichrome) indicated that the
      lungs in the low-dose group did not exhibit any progressive fibrotic changes.
      Whereas, the lungs in the high-dose group exhibited early delicate fibrosis from
      day 15, which progressed into the perivascular and peribronchiolar regions by day
      30. Interstitial fibrosis appeared at day 60 and became prominent by day 90,
      along with the additional appearance of pleural fibrosis. Accordingly, it would
      appear that a significant dose of welding-fume exposure was required to induce
      lung fibrosis.

PMID- 11509750
TI  - Quantification of changes in c-myc mRNA levels in normal human bronchial
      epithelial (NHBE) and lung adenocarcinoma (A549) cells following chemical
      treatment.
AB  - Lung tumors frequently exhibit altered expression of oncogenes and/or tumor
      suppressor genes. Although some of these alterations are believed to arise from
      chemical exposure, the ability of specific chemicals to cause distinct changes in
      gene expression is not well characterized. We previously reported the development
      of a quantitative reverse transcriptase/polymerase chain reaction (RT/PCR) method
      for measuring c-myc mRNA levels, and reported that c-myc proto-oncogene
      expression is significantly increased in small-cell lung carcinoma cells. In the
      present study, quantitative RT/PCR was used to assess the effect of model toxins
      cycloheximide (CHX), a protein synthesis inhibitor, and N-methyl-N'-nitro-N
      nitrosoguanidine (MNNG), a DNA alkylating agent, on c-myc mRNA levels in normal
      human bronchial epithelial (NHBE) and lung adenocarcinoma (A549) cells.
      Expression of c-myc was evaluated at 1-100 microM CHX and MNNG and was compared
      to the cytotoxic response as measured by the neutral red assay. Cycloheximide
      elicited a dose-dependent increase in c-myc mRNA levels in NHBE and A549 cells,
      but did not alter expression of the housekeeping gene beta-actin. A maximum
      increase for c-myc expression (200% of control) was observed 5 h after treatment
      with noncytotoxic concentrations. In contrast, MNNG elicited a dose-dependent
      decrease in c-myc expression in A549 cells, but no significant change in c-myc
      was observed in NHBE cells. The results from this study suggest that the
      quantitative RT/PCR method may be an appropriate technique for monitoring gene
      expression changes following chemical exposure. Hence, these types of studies may
      assist in the identification of specific chemicals which may induce the genetic
      alterations involved in the development of lung cancer as well as provide
      information relevant to the interactive effects of chemicals within complex
      mixtures.

PMID- 11509751
TI  - Ozone exposure enhances expression of cell-surface molecules associated with
      antigen-presenting activity on bronchoalveolar lavage cells in rats.
AB  - In this study, we investigated the effects of ozone (O3) exposure on expression
      of cell-surface molecules associated with antigen presentation and on accessory
      activity of bronchoalveolar lavage cells (BAL cells). Rats were exposed to 1 ppm
      O3 for 3 days. Expression of cell-surface molecules was measured by flow
      cytometry. Accessory activity of BAL cells was assessed by the allogeneic mixed
      lymphocyte reaction (MLR) and specific antigen-presenting activity. O3 exposure
      increased the expression of Ia, B7.1, B7.2, and CD11b/c on BAL cells.
      Morphological and immunological studies showed the Ia-positive cells to have
      monocyte-like features. Peripheral blood monocytes expressed Ia, B7.1, B7.2, and
      CD11b/c. The Ia expression on the monocytes was further increased by treatment of
      them with BAL fluid from O3-exposed rats (O3-BALF). Resident alveolar
      macrophages, however, did not express Ia antigen, and the Ia expression was not
      increased by O3-BALF. Neutrophils, which also infiltrated in response to O3
      exposure, did not express Ia, B7.1, and B7.2. Therefore, infiltrating monocytes
      may have caused the increased expression of Ia and B7 molecules on BAL cells
      exposed to O3. The accessory activity of BAL cells in terms of MLR and specific
      antigen-presenting activity was also enhanced by O3 exposure. The present study
      suggests that monocytes infiltrating in response to O3 exposure caused
      enhancements of the expression of Ia and costimulatory molecules on and the
      accessory activity of BAL cells.

PMID- 11509752
TI  - A PBPK modeling-based approach to account for interactions in the health risk
      assessment of chemical mixtures.
AB  - The objectives of the present study were: (1) to develop a risk assessment
      methodology for chemical mixtures that accounts for pharmacokinetic interactions
      among components, and (2) to apply this methodology to assess the health risk
      associated with occupational inhalation exposure to airborne mixtures of
      dichloromethane, benzene, toluene, ethylbenzene, and m-xylene. The basis of the
      proposed risk assessment methodology relates to the characterization of the
      change in tissue dose metrics (e.g., area under the concentration-time curve for
      parent chemical in tissues [AUCtissue], maximal concentration of parent chemical
      or metabolite [Cmax], quantity metabolized over a period of time) in humans,
      during mixed exposures using PBPK models. For systemic toxicants, an interaction
      based hazard index was calculated using data on tissue dose of mixture
      constituents. Initially, the AUCtarget tissue (AUCtt) corresponding to guideline
      values (e.g., threshold limit value [TLV]) of individual chemicals were obtained.
      Then, the AUCtt for each chemical during mixed exposure was obtained using a
      mixture PBPK model that accounted for the binary and higher order interactions
      occurring within the mixture. An interaction-based hazard index was then
      calculated for each toxic effect by summing the ratio of AUCtt obtained during
      mixed exposure (predefined mixture) and single exposure (TLV). For the
      carcinogenic constituents of the mixture, an interaction-based response
      additivity approach was applied. This method consisted of adding the cancer risk
      for each constituent, calculated as the product of q*tissue dose and AUCtt. The
      AUCtt during mixture exposures was obtained using an interaction-based PBPK
      model. The approaches developed in the present study permit, for the first time,
      the consideration of the impact of multichemical pharmacokinetic interactions at
      a quantitative level in mixture risk assessments.

PMID- 11509753
TI  - Toxicological interactions among arsenic, cadmium, chromium, and lead in human
      keratinocytes.
AB  - To evaluate health effects of chemical mixtures, such as multiple heavy metals in
      drinking water, we have been developing efficient and accurate hazard
      identification strategies. Thus, in this study, we determine the cytotoxicity of
      arsenic, cadmium, chromium, and lead, and characterize interactions among these
      metals in human epidermal keratinocytes. Three immortal keratinocyte cell lines
      (RHEK-1, HaCaT, and NM1) and primary keratinocytes (NHEK) were used. A
      statistical approach applying an additivity response surface methodology was used
      to test the validity of the additivity concept for a 4-metal mixture. Responses
      of the 4 keratinocyte strains to the metal mixture were highly dose-dependent. A
      growth stimulatory effect (hormesis) was observed in RHEK-1, NM1, and NHEK cells
      with the metal mixture at low concentrations (low ppb range). This hormesis
      effect was not significant in HaCaT. As the mixture concentration increased, a
      trend of additivity changed to synergistic cytotoxicity in all 4 cell strains.
      However, in NHEK, RHEK-1, and HaCaT, at the highest mixture concentrations
      tested, the responses to the metal mixtures were antagonistic. In NM1, no
      significant antagonistic interaction among the metals was observed. To explore a
      mechanistic basis for these differential sensitivities, levels of glutathione and
      metallothioneins I and II were determined in the keratinocyte cell strains.
      Initial data are consistent with the suggestion that synergistic cytotoxicity
      turned to antagonistic effects because at highest mixture exposure concentrations
      cellular defense mechanisms were enhanced.

PMID- 11509754
TI  - Oxidative stress and reactive nitrogen species generation during renal ischemia.
AB  - Previous evidence suggests that both oxygen radicals and nitric oxide (NO) are
      important mediators of injury during renal ischemia-reperfusion (I-R) injury.
      However, the generation of reactive nitrogen species (RNS) has not been evaluated
      in this model at early time points. The purpose of these studies was to examine
      the development of oxidant stress and the formation of RNS during I-R injury.
      Male Sprague-Dawley rats were anesthetized and subjected to 40 min of bilateral
      renal ischemia followed by 0, 3, or 6 h of reperfusion. Control animals received
      a sham operation. Plasma urea nitrogen and creatinine levels were monitored as
      markers of renal injury. Glutathione (GSH) oxidation and 4-hydroxynonenal (4-HNE)
      protein adducts were used as markers of oxidant stress. 3-Nitrotyrosine (3-NT)
      was used as a biomarker of RNS formation. Significant increases in plasma
      creatinine concentrations and urea nitrogen levels were found following both 3
      and 6 h of reperfusion. Increases in GSH oxidation, 4-HNE-protein adduct levels,
      and 3-NT levels were observed following 40 min of ischemia with no reperfusion.
      Since these results suggested RNS generation during the 40 min of ischemia, a
      time course of RNS generation following 0, 5, 10, 20, and 40 min of ischemia was
      evaluated. Significant increases in 3-NT generation was detected as early as 10
      min of ischemia and rose to values nearly 10-fold higher than Control at 40 min
      of ischemia. No additional increase was observed following reperfusion. The data
      clearly demonstrate that oxidative stress and RNS generation occur in the kidney
      during ischemia.

PMID- 11509755
TI  - Harmonization of cancer and noncancer risk assessment summarized the proceedings
      of a consensus-building workshop.

PMID- 11509756
TI  - The BCG vaccine: does it work?

PMID- 11509757
TI  - Who supervises the supervisors?

PMID- 11509758
TI  - Can this be conservation?

PMID- 11509759
TI  - Nitric oxide.
AB  - Nitric oxide (NO)--a 1:1 combination of the two most abundant gaseous elements-
      is a biological mediator of complexity, subtlety and protean effects. The history
      of its discovery as a mediator is fascinating, and its role in mammalian biology
      and medicine is proving to be of fundamental importance.

PMID- 11509760
TI  - Integration: farm and environment.
AB  - At a time when GM crops are being planted all around the globe, Europe appears to
      favour a more primitive and less productive agricultural system. Is the
      abandonment of 50 years of agricultural development the way forward or is there a
      rational alternative?

PMID- 11509761
TI  - Light of my life--messages in the dark.
AB  - Luminescent lures, counter-shading in the dark blue sea, flashes of light
      intensive enough to temporarily blind a predator, love fireworks in the night to
      impress a mate, and toadstools that glow to attract parasitic wasps--these are
      just some of the many examples of bioluminescence at work in Nature. But how is
      the biological light produced? What are its evolutionary roots? Why are there so
      many different uses for the light?

PMID- 11509762
TI  - Volunteers assess marine biodiversity.
AB  - Much less is known about marine biodiversity than that of terrestrial and
      freshwater environments. There is surprisingly little information about even the
      most common of organisms that live on the seashore. Science has limited resources
      to study them and volunteers can therefore make significant contributions. This
      article considers the value of a project in which volunteers are mapping the
      distribution and abundance of littoral animals and plants of the Northumberland
      coast.

PMID- 11509763
TI  - Computers, microscopes and cancer.
AB  - Computers and microscopes work hand in hand today. Together they offer the
      potential to enhance, analyse and store images, as well as creating the
      possibility of three- or four-dimensional pictures. The impact of these
      developments on cancer research is already apparent.

PMID- 11509764
TI  - Multiple factors in the reptile extinctions of the Cretaceous period.
AB  - The selective extinction of the dinosaurs and other giant reptiles has long been
      a topic of speculation and controversy. Everyone is familiar with the theory of
      the giant bollide colliding with Earth. But, would it not be more likely that
      that multiple factors acted over a relatively long period of time to produce this
      mass extinction?

PMID- 11509765
TI  - Where have all the flowers gone? Are our woodland flowers disappearing?
AB  - The owner of a wood in Norfolk once told me that he thought that the lily of the
      valley has declined over the last 20 years. In Wytham Woods near Oxford the dense
      bramble patches I studied in the 1970s didn't seem so thick ten years later. Were
      these slips of the memory or did Pete Seeger have a point with his 1961 song -
      Where have all the flowers gone?

PMID- 11509766
TI  - Who was... Frank Buckland?
AB  - Frank Buckland introduced salmon and trout to Australia. He was also one of the
      most popular writers on natural history in the 19th century and this interest,
      particularly in fish farming, rapidly overtook his work as a doctor.

PMID- 11509767
TI  - A grand old age.

PMID- 11509769
TI  - Litigation and laparoscopy.

PMID- 11509768
TI  - Tribute to Professor Carlo Romanini.

PMID- 11509770
TI  - Beta-hCG-negative ectopic pregnancy in the right tube.

PMID- 11509771
TI  - Survey of laparoscopic entry injuries provoking litigation.
AB  - STUDY OBJECTIVE: To examine injuries sustained during laparoscopic entry
      procedures that provoked malpractice claims in order to discern relative
      vulnerability of specific organs and differences in injury patterns, mortality,
      and financial awards, and specific entry devices involved in domestic claims
      versus those in other countries. DESIGN: Survey (Canadian Task Force
      classification II-2). SETTING: Insurance company records. INTERVENTIONS:
      Abstracts of malpractice allegations in 135 domestic cases insured by United
      States member companies of the Physician Insurers Association of America and 111
      cases by its non-United States affiliates were examined. MEASUREMENTS AND MAIN
      RESULTS: Most cases in the United States involved biliary-gastrointestinal
      surgery rather than gynecologic procedures; this was reversed for the non-United
      States database. Major vessel injury was proportionally more common in the
      domestic group. Small bowel led the group of structures injured. Most injuries
      involved trocars of various types (185), including blunt types (16); and needle
      injuries were noted in 39 cases. Injuries were recognized more immediately in the
      United States, and mortality was related to delay in diagnosis of bowel
      penetration. Indemnity payments were greater for serious nonfatal injuries versus
      deaths in the United States, but the opposite was true in other countries.
      CONCLUSION: Probably no needle-trocar system can guarantee avoidance of injury
      during laparoscopic entry, especially when the trajectory of insertion puts great
      vessels at risk. Bowel injuries occur during open as well as closed techniques of
      insertion, and with optical trocar systems as well. Vascular injury is usually
      obvious, but delayed recognition of loss of bowel integrity is related to
      increased mortality, especially in patients over 60 years of age.

PMID- 11509772
TI  - Fertility outcome after tubal anastomosis by laparoscopy and laparotomy.
AB  - STUDY OBJECTIVE: To evaluate fertility outcome and benefit of laparoscopic tubal
      anastomosis compared with laparotomy. DESIGN: Retrospective study (Canadian Task
      Force classification II-2). SETTING: University hospital. PATIENTS: Eighty-one
      women requesting reversal of sterilization. Fertility outcome was analyzed in 76
      patients for a minimum of 6 months. INTERVENTION: Laparoscopic tubal anastomosis
      in 37 women and abdominal tubal anastomosis in 44. MEASUREMENTS AND MAIN RESULTS:
      In both groups anastomosis was performed in two layers with four stitches using
      microsurgical technique. Overall pregnancy rates were 80.5% in the laparoscopy
      and 80.0% in the laparotomy group. The mean interval from operation to pregnancy
      was similar in the two groups (p = 0.9). Mean operating time was significantly
      longer for laparoscopy (201.9 +/- 33.8 min) than for laparotomy (148.7 +/- 32.5
      min), including diagnostic laparoscopy. However, mean hospital stay was shorter
      for laparoscopy than for laparotomy (3.3 +/- 2.0 vs 6.1 +/- 0.6 days, p <0.05).
      CONCLUSION: Laparoscopic tubal anastomosis is less invasive and could be an
      alternative to laparotomy for reversal of tubal sterilization. Advanced
      laparoscopic equipment and much experience could enhance the pregnancy rate and
      reduce operating time.

PMID- 11509773
TI  - Pelviscopic reversal of tubal sterilization with the one- to two-stitch
      technique.
AB  - STUDY OBJECTIVE: To describe 28 pelviscopic proximal reversals of tubal
      sterilization. DESIGN: Cohort study (Canadian Task Force classification II-2).
      SETTING: University-affiliated hospital. PATIENTS: Twenty-eight women.
      INTERVENTIONS: Twenty-two women underwent bilateral and six unilateral tubal end
      to-end anastomosis through a catheter introduced through the working channel of a
      hysteroscope for a combined hysteroscopic-laparoscopic operation. MEASUREMENTS
      AND MAIN RESULTS: In the two-stitch technique the first stitch adapted the
      mesosalpinx and the second (4-0 or 6-0 material) to unite the tube muscularis. In
      some cases a third stitch was applied to either the muscularis or mesosalpinx. In
      all cases the wound was sealed with tissue col at the end of the procedure. Tubal
      patency was achieved in 95% of bilateral anastomoses and 100% of unilateral ones.
      Seventeen pregnancies (61%) were achieved within a minimum of 6 months and a
      maximum of 4 years. Fifteen patients (54%) had an intrauterine pregnancy with
      normal delivery and two (7%) had a tubal pregnancy. No abortions occurred.
      CONCLUSION: Laparoscopic end-to-end anastomosis is a suitable surgical
      alternative to tubal end-to-end anastomosis by laparotomy and has all the
      advantages of a laparoscopic procedure.

PMID- 11509774
TI  - A multicenter evaluation of endometrial ablation by Hydro ThermAblator and
      rollerball for treatment of menorrhagia.
AB  - STUDY OBJECTIVE: To compare results of endometrial ablation using the Hydro
      ThermAblator (HTA) and rollerball. DESIGN: Prospective, randomized study
      (Canadian Task Force classification I). SETTING: Nine private practice and
      university centers in the United States. PATIENTS: Two hundred seventy-six women
      with menorrhagia due to benign causes. INTERVENTION: Endometrial ablation with
      the HTA (187 women) or rollerball (89). MEASUREMENTS AND MAIN RESULTS: Menstrual
      diaries were kept for 2 weeks and 3, 6, and 12 months after treatment. Reduction
      in diary scores to 75 or lower at 12 months was considered a success. For
      patients treated and followed according to protocol, success rates were 77% for
      HTA and 82% for rollerball. Amenorrhea rates at 12 months were 40% and 51%,
      respectively. CONCLUSION: Endometrial ablation with the HTA is safe and
      effective. It offers an advantage over rollerball ablation of being an office
      based procedure, which reduces anesthesia requirements and obviates problems of
      fluid absorption.

PMID- 11509775
TI  - Adhesion formation after laparoscopic resection of uterosacral ligaments in women
      with endometriosis.
AB  - STUDY OBJECTIVE: To analyze the risk of postoperative adhesions in women who
      undergo laparoscopic surgical management of deep endometriosis infiltrating the
      uterosacral ligaments (USL). DESIGN: Retrospective analysis (Canadian Task Force
      classification II-2). SETTING: University-affiliated hospital. PATIENTS: Forty
      six women with deep endometriosis infiltrating the USL. INTERVENTION:
      Laparoscopic resection of all USL with deep endometriotic lesions and excision of
      all other endometriotic lesions, followed by second-look laparoscopy.
      MEASUREMENTS AND MAIN RESULTS: At second-look laparoscopy, 15 patients (32.6%)
      had no adhesions at the site where the USL had been resected, 24 (52.2%) had
      filmy avascular adhesions, and 7 (15.2%) had dense or vascular adhesions. No
      patient had adhesions of the binding type. Only two factors, the revised American
      Fertility Association (rAFS) score at initial laparoscopy and surgical modality
      (unilateral resection of the right USL, unilateral resection of the left USL,
      bilateral resection of USL) had a statistically significant influence on the risk
      of postoperative adhesions occurring. After adjustment, the relation with initial
      rAFS stage and surgical modality remained significant in the stepwise logistic
      regression model. CONCLUSION: These encouraging results are particularly
      interesting for patients with infertility due to pelvic pain syndrome. Second
      look laparoscopy should not be performed routinely after laparoscopic management
      of deep endometriosis infiltrating the USL. We propose that it be reserved for
      women with rAFS stages III and IV endometriosis, especially when lesions are
      located on the left side.

PMID- 11509776
TI  - Extraperitoneal approach to laparoscopic Burch colposuspension.
AB  - STUDY OBJECTIVE: To evaluate 3-year outcomes of extraperitoneal laparoscopic
      colposuspension in treating genuine stress incontinence. DESIGN: Retrospective
      review (Canadian Task Force classification II-2). SETTING: University-based,
      tertiary-level center for endoscopic surgery. PATIENTS: One hundred sixty women
      with genuine stress incontinence with bladder neck hypermobility. INTERVENTION:
      Extraperitoneal space was created with CO2 through a 10-mm midline port 2 cm
      above the pubic hairline. A pair of sutures was inserted at the level of
      midurethral and urethrovesical junction, fixing them to Cooper's ligament on each
      side with proper tension. MEASUREMENTS AND MAIN RESULTS: Of 160 women, 10 were
      lost to follow-up. On follow-up questionnaire sent to 150 patients, 148 (98.7%)
      were pleased with the results of surgery. Stress incontinence was cured in 136
      women (90.7%) after a minimum of 3 years' follow-up. CONCLUSION: Cure rates for
      extraperitoneal colposuspension were similar to those reported for traditional
      laparoscopic or laparotomy Burch procedures; however, this is a more direct
      method to expose the space of Retzius, thus eliminating the need to open and
      close peritoneum.

PMID- 11509777
TI  - Comparison of tissue injury between laparosonic coagulating shears and
      electrosurgical scissors in the sheep model.
AB  - STUDY OBJECTIVE: To compare laparosonic coagulating shears (LCS), which use
      ultrasonic energy, and unipolar diathermy scissors with respect to depth of
      tissue injury. DESIGN: Prospective observational study (Canadian Task Force
      classification I). SETTING: A reproduced surgical setting. SUBJECTS: An
      anesthetized sheep. INTERVENTION: We laparoscopically harvested uterine horn and
      bowel tissue. MEASUREMENTS AND MAIN RESULTS: Tissue was transected while
      hemostasis was maintained. Two pathologists examined tissue independently, and
      each was blinded as to the instrument used for harvesting. Clinical
      characteristics and tissue injury created by the instruments were compared.
      CONCLUSION: Subjectively, LCS appeared to produce less smoke plume than diathermy
      scissors. It also produced greater tissue damage than unipolar electrosurgery on
      settings of 35 W cut and 30 W coagulate.

PMID- 11509779
TI  - Laparoscopic Burch colposuspension for recurrent stress urinary incontinence.
AB  - STUDY OBJECTIVE: To evaluate the effectiveness of laparoscopic Burch
      colposuspension in the treatment of recurrent stress urinary incontinence in
      women with previous vaginal or abdominal retropubic continence surgery. DESIGN:
      Retrospective analysis over 36 months (Canadian Task Force classification III).
      SETTING: Community hospital. PATIENTS: Thirty-three consecutive patients.
      INTERVENTION: Laparoscopic Burch colposuspension. MEASUREMENTS AND MAIN RESULTS:
      Data were obtained by retrospective chart review, telephone interviews, and
      follow-up physical examinations. Of the 33 patients, 17 (52%) had undergone open
      retropubic procedures (Burch or Marshall-Marchetti-Krantz), 11 (33%) had had
      vaginal retropubic needle suspension, and 5 (15%) pubovaginal sling operation.
      Additional laparoscopic and/or vaginal reconstructive surgery was completed in 32
      women (97%) at time of laparoscopic Burch. Average overall operating time was 165
      minutes (range 60-287 min), mean estimated blood loss was 178 ml (range 50-600
      ml), and hospital stay was 1.1 days. Three intraoperative complications occurred,
      two cystotomies and one serosal bowel injury. Postoperative objective evaluation
      over average follow-up of 18.6 months revealed a 90% stress urinary incontinence
      cure rate. CONCLUSION: Laparoscopic Burch colposuspension is safe and effective
      treatment of recurrent stress urinary incontinence in women who have undergone
      previous procedures for retropubic continence.

PMID- 11509778
TI  - Comparison of microlaparoscopy and conventional laparoscopy for tubal
      sterilization under local anesthesia with mild sedation.
AB  - STUDY OBJECTIVE: To compare tubal sterilization performed by microlaparoscopy and
      conventional laparoscopy. DESIGN: Prospective, randomized trial (Canadian Task
      Force classification I). SETTING: Gazi University School of Medicine. PATIENTS:
      Twenty women undergoing surgical sterilization. INTERVENTION: Ten sterilizations
      by conventional laparoscopy and 10 by microlaparoscopy. MEASUREMENTS AND MAIN
      RESULTS: The techniques were comparable in quality of visualization, operating
      time, amount of drugs used for sedation and local anesthesia, and intraoperative
      pain scores. However, the postoperative analgesic requirement was significantly
      less in women treated by by microlaparoscopy. CONCLUSION: Tubal sterilization by
      microlaparoscopy does not differ greatly from conventional laparoscopic
      sterilization.

PMID- 11509780
TI  - Diagnostic and operative transvaginal hydrolaparoscopy for infertility and pelvic
      pain.
AB  - STUDY OBJECTIVE: To review our experience with diagnostic and operative
      transvaginal hydrolaparoscopy (THL), a procedure that is less invasive than
      operative laparoscopy. DESIGN: Prospective, observational cohort study (Canadian
      Task Force classification II-2). SETTING: Private institute and university
      affiliated hospital. PATIENTS: Twenty-nine women with infertility and 11 with
      pelvic pain. INTERVENTIONS: Diagnostic and operative THL. MEASUREMENTS AND MAIN
      RESULTS: Thirty-five (88%) diagnostic THLs were performed in the office and the
      other five were done in hospital for insurance reasons; all six operative THLs
      were performed in the office under conscious sedation. The procedure was
      conclusive (all organs seen) in 37 patients (93%). Based on THL, no further
      surgical intervention was recommended in 18 (62%) infertile women and 5 (45%) of
      those with pain. Further surgical intervention was required in 5 (56%) of 9
      infertility patients with a previous normal hysterosalpingogram (HSG) and 6 (32%)
      of 19 infertility patients with no previous HSG. CONCLUSION: Transvaginal
      hydrolaparoscopy can be performed in the office with minimal pain, with a
      conclusive examination anticipated in 93% of cases. The procedure is more
      accurate than HSG and similar to laparoscopy.

PMID- 11509781
TI  - Hysteroscopic findings in 344 women with recurrent spontaneous abortion.
AB  - STUDY OBJECTIVE: To evaluate the prevalence of different anatomic factors in
      women with recurrent spontaneous abortion (RSA). DESIGN: Retrospective analysis
      over 9 years (Canadian Task Force classification II-2). SETTING: University
      hospital-affiliated endoscopic unit. PATIENTS: Three hundred forty-four
      consecutive patients with RSA and 922 controls referred for abnormal uterine
      bleeding. INTERVENTION: Diagnostic hysteroscopy. MEASUREMENTS AND MAIN RESULTS:
      Major and minor uterine mullerian abnormalities (septate, unicornuate uteri) were
      found significantly more often in women with RSA than in controls (32% vs 6%, p
      <0.001). The frequency of acquired uterine anomalies (submucous myomas, polyps)
      was significantly higher in controls (32% vs 9%, p <0.001). No significant
      differences were observed between groups in frequency of adhesions (4% vs 2%).
      CONCLUSION: Major mullerian uterine abnormalities are associated with RSA, and
      minor uterine anomalies may be correlated with an increased risk of recurrent
      miscarriage.

PMID- 11509783
TI  - A single, continuous spiraling suture for uterine wall reconstruction after
      laparoscopic enucleation of intramural myomas.
AB  - After laparoscopic enucleation of intramural myomas in eight women, the uterine
      wall defect was reconstructed with a single continuous spiraling suture. The
      procedure contained cost and reduced operating time. No patients had
      postoperative intramural hematoma. Although this is a reproducible method of
      laparoscopic uterine wall reconstruction, long-term results must be obtained to
      determine safety in pregnancy and extent of postoperative adhesions.

PMID- 11509782
TI  - Classification for endoscopic treatment of mullerian anomalies with an
      obstructive cervix.
AB  - STUDY OBJECTIVE: To describe our classification according to severity of
      developmental mullerian anomalies with obstructed cervix. DESIGN: Retrospective
      review (Canadian Task Force classification II-2). SETTING: University-based,
      tertiary-level center for endoscopic surgery. PATIENTS: Ten women with
      developmental mullerian anomalies with obstructed cervix. INTERVENTION: Patients
      with didelphic uterus with a rudimentary nonfunctional horn and hypoplastic
      cervix (type 1) underwent hemihysterectomy or diagnostic endoscopy. Those with
      agenesis of cervix with normal uterus (type 2) had uterovaginal canalization or
      neocervix with full-thickness skin graft. Women with identical didelphic uteri
      and hypoplastic cervix (type 3) underwent uterovaginal canalization with or
      without endometrial ablation or hemihysterectomy. Patients with didelphic uterus
      with a rudimentary horn and hypoplastic cervix (type 4) had laparoscopic
      hemihysterectomy. Those with agenesis of the vagina and cervix but with
      functional endometrium (type 5) had laparoscopic-assisted full-thickness skin
      graft. MEASUREMENTS AND MAIN RESULTS: Average duration of surgery was 60 to 210
      minutes. There were no intraoperative complications. Patients with type 1 anomaly
      are continuing infertility treatment. All three patients in type 2 continue to
      have regular menses without dysmenorrhea. In those with type 3 conditions,
      hemihysterectomy was performed in one woman and uterovaginal canalization was
      performed on the hypoplastic cervix in another. After the neocervix was created,
      endometrial ablation was performed. No evidence of cervical obstruction or
      hematometra was found in either patient. The patient with type 4 anomaly
      continues to have regular menstrual periods without dysmenorrhea. Women with type
      5 disorder had good healing of vaginal skin grafts. CONCLUSION: This
      classification helps identify mullerian anomalies in relation to obstructive
      cervix. It is useful in categorizing the disorders and determines management
      strategies and prognosis.

PMID- 11509784
TI  - Laparoscopic ureteroureteral anastomosis on the distal ureter.
AB  - Repair of ureteral injury involving the distal ureter traditionally required
      laparotomy. Ureteroureteral anastomosis is not usually advocated due to technical
      difficulties and poor outcomes. Laparoscopy overcomes these difficulties and
      allows correction of distal ureteral injuries.

PMID- 11509785
TI  - Laparoscopic creation of a neovagina in Mayer-Rokitansky-Kuster-Hauser syndrome
      by modification of Vecchietti's procedure.
AB  - We performed a modified Fedele technique for laparoscopic creation of a neovagina
      by Vecchietti's method to treat vaginal aplasia in three patients with Mayer
      Rokitansky-Kuster-Hauser syndrome. Three beads forming a triangle, anchored to a
      disposable syringe mould, were applied to the vaginal dimple and pulled upward by
      two polypropylene sutures, and passed through the potential neovaginal space
      created laparoscopically. The women sat on ordinary bicycle seats to provide
      pressure from below, resulting in formation of neovagina over 10 to 12 days. Good
      results were obtained in all three women in both anatomy and sexual function.

PMID- 11509786
TI  - Benefits of high epigastric port placement for removing the very large uterus.
AB  - Six laparoscopic-assisted vaginal hysterectomies were performed in women with
      huge uterine myomata. Because traditional four-puncture technique had limitation
      in these cases, high epigastric port placement provided an excellent operative
      field.

PMID- 11509787
TI  - Usefulness of long-jaw forceps in laparoscopic cornual resection of interstitial
      pregnancies.
AB  - Although laparoscopic surgery could be an option for treating interstitial
      pregnancies, it has not gained wide acceptance largely because of difficulty
      achieving hemostasis. To overcome this, we employed long-jaw forceps in three
      cases of interstitial pregnancy that were successfully treated by laparoscopic
      cornual resection. The forceps grasped a relatively large portion of pregnant
      myometrium without slipping, thus securing hemostasis and facilitating suturing.

PMID- 11509788
TI  - The Endosquid, a new device for laparoscopic Pomeroy tubal ligation.
AB  - The Pomeroy method is a most widely practiced and most familiar form of tubal
      ligation. It traditionally requires laparotomy or multiple-puncture laparoscopic
      suturing, which is not a realistic option for the average endoscopist. We
      designed a 5-mm device, the Endosquid, to reproduce Pomeroy tubal ligation
      laparoscopically using a single 5-mm accessory puncture site. It is able to
      ligate, transect, and remove a loop of isthmic tube. We tested the Endosquid in a
      porcine model by ligating 25 bicornuate uterine horns and aortas. Ligation times
      averaged less than 5 minutes for each application. Gross and histologic
      evaluation of ligation specimens performed at necropsy confirmed correct
      placement. Blood loss was negligible and there were no operative complications.

PMID- 11509789
TI  - Operative culdolaparoscopy: a new approach combining operative culdoscopy and
      minilaparoscopy.
AB  - The tendency is to use small cannulas for operative laparoscopy; however, working
      with these cannulas may have technical limitations. We developed a technique for
      performing appendectomy combining culdoscopy and minilaparoscopy. It uses 3- or 5
      mm abdominal cannulas, and the large 10- or 12-mm cannula is inserted into the
      posterior vaginal fornix under laparoscopic surveillance. The vaginal port is
      used to introduce operative instruments and extract specimens, and for vision.
      Culdolaparoscopy avoids additional or large abdominal ports, thus overcoming
      limitations of small cannulas.

PMID- 11509790
TI  - Uterine restoration after repeated expulsion of myomas after uterine artery
      embolization.
AB  - A patient passed infarcted myomas 21, 27, and 35 days after uterine artery
      embolization. Transvaginal ultrasound examination did not reveal a myoma and her
      menstruation became normal with minimal bleeding. Uterine artery embolization and
      expulsion of myomas vaginally can eliminate intramural and submucous myomas.

PMID- 11509791
TI  - Thoracic endometriosis syndrome resembling pulmonary embolism.
AB  - A 32-year-old infertility patient with a previous diagnosis of stage IV
      endometriosis experienced shortness of breath and chest pain. She was diagnosed
      with a pulmonary embolism by spiral volumetric computed tomography (SVCT) and
      anticoagulated during hospitalization, although no history of thrombosis was ever
      identified. She continued to have intermittent symptoms of chest pain, back pain,
      and shortness of breath for the next 1.5 months. Repeat SVCT revealed a large,
      right-sided pleural effusion with associated consolidation but no evidence of
      pulmonary embolism. To obtain a definitive diagnosis, a thoracoscopic pleural
      biopsy was performed and showed thoracic endometriosis involving the pleura. The
      patient desired to retain her fertility and opted for treatment with depot
      medroxyprogesterone. She has been asymptomatic for 2 years with this treatment.
      This case illustrates the importance of recognizing thoracic endometriosis
      syndrome and the difficulty diagnosing this condition considering its nonspecific
      features.

PMID- 11509792
TI  - Incarcerated hernia in a 5-mm cannula wound.
AB  - Laparoscopic suturing and repairing of the fascial opening at 10- to 12-mm
      cannula puncture sites is well established; however, closing a 5-mm cannula wound
      is not well documented. We often leave the wound open without suture and cover it
      with gauze after removing the surgical drainage tube. An unusual early
      postoperative complication of laparoscopic surgery was an incarcerated hernia in
      a 5-mm cannula site. The 9-year-old girl underwent laparoscopic surgery due to an
      8-cm ovarian mature teratoma. After 7 days, she came to our hospital because of a
      protruding mass in the left cannula wound. The mass was excised, and incarcerated
      fallopian tube torsion with necrotic change was diagnosed.

PMID- 11509793
TI  - Axonal damage to the left musculocutaneous nerve of the left biceps muscle during
      laparoscopic surgery.
AB  - The probable etiology of axonal damage to the left musculocutaneous nerve (motor
      branch) of the left biceps branchii during a laparoscopic procedure was the
      position in which the patient was maintained. As a result of unintentional change
      in the angle of the arm from 90 to approximately 120 degrees while in steep
      Trendelenburg position, the arm might have suffered hyperextension, resulting in
      pressure on and stretching of the brachial plexus nerve. This in turn might be
      the cause of neurologic damage. We recommend taking steps to prevent such
      occurrences, such as tying the patient's arms parallel to the body.

PMID- 11509794
TI  - Laparoscopic unwinding and cystectomy of twisted dermoid cyst during second
      trimester of pregnancy.
AB  - A woman in the sixteenth week of pregnancy experienced acute abdominal pain, and
      magnetic resonance imaging suggested a dermoid cyst. Laparoscopic unwinding and
      cystectomy of the twisted cyst was performed successfully.

PMID- 11509795
TI  - Global Congress of Gynecologic Endoscopy, 30th annual meeting of the American
      Association of Gynecologic Laparoscopists. San Francisco, California, USA.
      November 16-19, 2001. Abstracts.

PMID- 11509796
TI  - Influence of age on the prognosis of renal transplant recipients.
AB  - With aging, morphologic organ changes due to arteriosclerosis, hypertension, or
      diabetes increase, and renal transplantation tends to become less successful. We
      analyzed the outcome of transplantation in 123 recipients who underwent renal
      transplantation between January 1988 and December 1989. We assessed patient and
      graft survival after 1, 5, and 6 years as well as mortality and transplant
      failure and the incidence of rejections. We compared the results of patients aged
      under 60 years (group 1, n = 60) with the findings of patients aged over 60 years
      (group 2, n = 63). Immunosuppression was with cyclosporin A and prednisolone
      without exception. In patients under the age of 60, the overall patient survival
      at 1, 5, and 6 years was 97, 95, and 90% and was significantly compromised in
      recipients over the age of 60 (92, 80, and 75%). The 1-, 5- and 6-year graft
      survival rates were 92, 90, and 90% in recipients aged over 60 years and 88, 82,
      and 79% in recipients under the age of 60 years. The incidence of rejection was
      significantly higher in recipients under the age of 60. Patient mortality was
      mainly due to cardiovascular complications and transplant failure mainly related
      to transplant thrombosis. In older patients, renal transplantation is thought to
      be an option of survival rate improvement in comparison with hemodialysis. The
      incidence of transplant rejection is significantly lower, and this indicates a
      promising result regarding the long-term prognosis. As cardiovascular
      complications present as the main mortality factors of both transplant and
      patient, the prognosis is considered to be highly dependent on screening and
      treatment of these risk factors.

PMID- 11509797
TI  - Leukocyte, platelet and endothelial activation in patients with acute renal
      failure treated by intermittent hemodialysis.
AB  - BACKGROUND: Using different types of dialysis membranes to treat acute renal
      failure (ARF), clinical and experimental studies have demonstrated discordant
      results relatively to the effect of membrane bioincompatibility on patient
      outcome. Nevertheless, there are few data on the biocompatibility indices in
      patients with ARF who need to be treated by hemodialysis. OBJECTIVE: To
      characterize the impact of intermittent hemodialysis (IHD) on indices of
      leukocyte, platelet and endothelial activation in patients with ARF. PATIENTS AND
      METHODS: We prospectively studied 27 patients with severe ARF treated by IHD.
      They were characterized relatively to gender, age, ARF etiology, urinary output
      per 24 h, Simplified Acute Physiology Score (SAPS), number of dialysis sessions
      and outcome. We evaluated the effect of hemodialysis with two types of low-flux
      dialyzers (cuprophane and polysulfone dialyzers) on plasma concentrations of
      soluble TNF-RI (TNF-sR55), TNF-RII (TNF-sR75), interleukin (IL)-6, soluble CD23
      molecule, soluble P-selectin and von Willebrand factor (vWF). RESULTS: There were
      no significant differences between the two groups of patients dialyzed with
      cellulose-based and synthetic membranes in terms of age, sex, urinary output per
      24 h, SAPS, number of dialysis sessions and mortality. We verified high plasma
      concentrations of TNF-sR55, TNF-sR75, IL-6, sCD23, sP-selectin and vWF in the
      global population studied. Patients dialyzed with cuprophane membranes showed
      significantly lower pre- and postdialysis concentrations of sP-selectin than
      patients dialyzed with polysulfone membranes. After a hemodialysis session, with
      correction for differences of blood hematocrit, we did not observe any
      significant modification in the concentrations of TNF-sR55, TNF-sR75, IL-6, sP
      selectin and vWF of the plasma. On the other hand, a significant increase of
      sCD23 molecule was found in the group dialyzed with polysulfone membranes (p =
      0.009). CONCLUSIONS: The group of 27 patients with ARF who needed IHD, showed
      increased plasma concentrations of some leukocyte, platelet and endothelial
      activation markers (TNF-sR55, TNF-sR75, IL-6, sCD23, sP-selectin and vWF). These
      mediators characterize the inflammatory and procoagulant state associated with
      this pathologic condition. After a hemodialysis session with these low-flux
      membranes (cellulose-based and polysulfone membranes), we did not observe any
      significant variation in the concentrations of TNF-sR55, TNF-sR75, IL-6, sP
      selectin and vWF of the plasma. Patients dialyzed with polysulfone membranes
      presented higher basal plasma concentrations of sP-selectin and significant
      postdialysis increase of plasma concentrations of CD23 molecule compared to
      patients dialyzed with cuprophane dialyzers.

PMID- 11509798
TI  - Study of lead exposure from automobile exhaust as a risk for nephrotoxicity among
      traffic policemen.
AB  - BACKGROUND: Traffic policemen are the most exposed population to lead (Pb) from
      automobile exhaust. There has been increasing concern about the possible harmful
      effects of Pb from automobile exhaust on health of traffic policemen. However, no
      such study was concerned with the impact of Pb exposure on renal function among
      them. Therefore, we aimed to study the effect of Pb exposure from automobile
      exhaust on renal integrity among traffic policemen. METHODS: Markers of tubular
      damage [urinary excretion of beta(2)-microglobulin (beta(2)M), N-acetyl-beta-D
      glucosaminidase (NAG), alkaline phosphatase (ALP) and gamma-glutamyl transferase
      (gamma-GT)], a marker of glomerular injury (albuminuria), and markers of
      glomerular filtration [serum creatinine, serum beta(2)M and blood urea nitrogen
      (BUN)] were determined in 43 traffic policemen (Pb-exposed group) and 52 matched
      healthy persons (control group). Pb levels in blood, urine, hair and nails were
      determined in the two groups as exposure indices of Pb. RESULTS: The results
      obtained show that the Pb-exposed group had higher Pb levels in blood, urine,
      hair and nails than the controls. Among the Pb-exposed group, Pb levels in blood,
      hair and nails showed significant and positive correlations with the duration of
      exposure to Pb which is measured as the duration of employment. Among the studied
      markers of kidney damage, urinary excretion of NAG and albumin were significantly
      higher in the Pb-exposed group than in the controls. Urinary excretion of NAG was
      positively correlated with duration of exposure, blood Pb and nail Pb. Urinary
      albumin was positively correlated with duration of exposure, blood Pb and hair
      Pb. The other markers of kidney damage were neither elevated nor correlated with
      exposure indices of Pb. CONCLUSION: Traffic policemen are liable to Pb toxicity,
      and the determination of Pb in blood, hair and nails are good markers of such
      toxicity. In these exposure conditions, kidney damage is possible. Such damage is
      both tubular and glomerular in nature and can be documented by determination of
      the urinary excretion of NAG and albumin.

PMID- 11509799
TI  - Risk factors for hypertension in chronic hemodialysis patients: baseline data
      from the HEMO study.
AB  - A cross-sectional analysis was performed to determine risk factors associated
      with hypertension in 1,238 chronic hemodialysis patients upon enrollment into the
      HEMO Study. The mean pre- and post-dialysis systolic blood pressure were 152.4 +/
      25.0 (mean +/- SD) and 137.8 +/- 24.6 mm Hg, respectively. The mean pre- and
      post-dialysis diastolic blood pressures were 82.1 +/- 14.8 and 74.7 +/- 13.8 mm
      Hg, respectively. Less than 30% of the study cohort had blood pressures that were
      normotensive by JNC VI guidelines. Risk factors associated with higher pre- and
      post-dialysis systolic blood pressures included the presence of diabetes
      mellitus, older age, increased number of prescribed antihypertensive medications,
      lower hematocrit, and absence of arrhythmias. Variables associated with higher
      pre- and post-dialysis diastolic blood pressures included younger age, increased
      number of prescribed anti-hypertensive medications and absence of arrhythmias.
      There was also a nonlinear relationship between blood pressure and prescribed
      total ultrafiltration volume. A total ultrafiltration volume of >2.5 kg was
      associated with an elevation in pre-dialysis systolic and diastolic blood
      pressures. A total ultrafiltration volume of < or =2.5 kg was associated with an
      elevation in post-dialysis systolic and diastolic blood pressures. These data on
      ultrafiltration volume suggest that higher pre-dialysis blood pressures may be
      associated with excessive interdialytic weight gains due to patient noncompliance
      with fluid restriction and that higher post-dialysis blood pressures may be
      associated with a prescribed dry weight that is higher than the patient's true
      dry weight. Better management of these parameters may improve the prevalence and
      severity of hypertension in this population.

PMID- 11509800
TI  - Heparin-induced skin necrosis in a patient with end-stage renal failure and
      functional protein S deficiency.
AB  - Skin ulceration is a well-characterized thrombotic complication of the heparin
      induced thrombocytopenia (HIT) syndrome. We present the case of a 73-year-old
      diabetic woman nearing end-stage renal failure who developed extensive upper
      thigh, abdominal and buttock ulceration following initiation of subcutaneous
      heparin for prophylaxis against deep vein thrombosis. A preliminary diagnosis of
      calciphylaxis was made based on the classical distribution and macroscopic
      appearance of the ulceration in a patient with end-stage renal failure and
      secondary hyperparathyroidism. However skin biopsy showed complete absence of
      calcium deposits in the dermal microvasculature. The presence of extensive
      microthrombi within dermal vessels prompted serologic testing to detect a
      prothrombotic state. We identified the combined presence of heparin-dependent
      platelet activating (HIT) antibodies and functional protein S deficiency. To our
      knowledge this is the first reported case of a dialysis patient presenting with
      skin ulceration induced by heparin and protein S deficiency. This case highlights
      the importance of a skin biopsy and testing for a hypercoaguable state in
      patients with end-stage renal disease and skin ulceration. We suggest that HIT
      antibodies should be requested in all dialysis patients presenting with skin
      ulceration.

PMID- 11509802
TI  - Long-term impact of hepatitis B, C virus infection on renal transplantation.
AB  - Chronic liver disease and its complications are major problems in renal
      transplant recipients. Our aim was to elucidate the influence of hepatitis B, C
      virus infection on the long-term outcome of renal transplantation. Four hundred
      and seventy-seven patients who received renal transplantation between January
      1984 and December 1999, and who were followed up at our hospital were enrolled.
      HBsAg was detected by the RIA method and anti-HCV Ab was assayed by the second
      generation RIA kit. SGOT/ SGPT were checked every 3 months. Hepatoma was
      diagnosed by dynamic CT scan, elevated alpha-fetoprotein, hypervascularity by
      angiography and confirmed by pathological examination. The prevalence of HBV,
      HCV, coinfected HBV/HCV was 9.9% (n = 47), 28.5% ( n = 136), 3.1% (n = 15),
      respectively. The incidences of hepatoma in the HBV-/HCV-, HBV-/HCV+, HBV+/HCV-,
      HBV+/HCV+ groups were 1.4% (n = 4), 4.4% (n = 6), 6.4% (n = 3), 6.7% (n = 1),
      respectively (p = 0.114). The incidences of liver cirrhosis/hepatic failure were
      3.2% (n = 9), 6.6% (n = 9), 21.3% (n = 10), 20% (n = 3), respectively (p <
      0.001). The frequencies of chronic liver disease were 10.4% (n = 29), 45.6% (n =
      62), 66% (n = 31), 80% (n = 12), respectively (p < 0.001). Patient and graft
      survival rates were lower in the HBV-infected group than in the other groups. Cox
      regression analysis revealed that HBV infection is likely an independent risk
      factor for patient mortality although the statistical significance was only
      borderline. Patients with HBV as well as HCV infection were not at risk of graft
      loss according to this model of analysis. Patients with HBV infection showed
      higher incidences of hepatoma, hepatic failure, graft failure and death.
      Therefore, HBV-infected patients who are candidates for renal transplantation
      should be carefully evaluated. It seems that HCV infection has little influence
      on the outcome of renal transplant recipients. A longer period of follow-up is
      needed to clarify the impact of HCV on renal transplant recipients.

PMID- 11509801
TI  - Reduction of the homocysteine plasma concentration by intravenously administered
      folinic acid and vitamin B(12) in uraemic patients on maintenance haemodialysis.
AB  - BACKGROUND: Hyperhomocysteinaemia is an independent cardiovascular risk factor
      which can induce vascular lesions, thus contributing to the early development of
      atherosclerosis. Low-dose folic acid supplementation reduces the pretreatment
      homocysteine plasma levels by 25-35%. Recent studies report that higher
      intravenous or oral administration of the active form of folic acid reduces the
      homocysteine plasma concentration by nearly 70%. The reduction could also be
      influenced by the thermolabile variant of methylenetetrahydrofolate reductase
      (tMTHFR) and by the dialysis modality. METHODS: A cross-sectional clinical study
      was performed to evaluate the effect of a drug containing folinic acid and
      vitamin B(12) on the plasma homocysteine concentration and whether this variable
      could also be influenced by the presence of a genetic variant of the methionine
      pathway and the use of different dialysis modalities. The plasma homocysteine
      concentration was measured in 55 patients undergoing haemodialysis, 27 of whom
      have been treated intravenously for megaloblastic anaemia using a drug containing
      low concentrations of folinic acid and vitamin B(12) at the end of each dialysis
      session for 6 months. The presence of tMTHFR was sought by molecular analysis,
      and the role of the dialysis modality was also investigated. RESULTS: The
      patients given the folic acid treatment had lower homocysteine plasma levels than
      those not so treated. The plasma homocysteine concentration was significantly
      higher in the tMRHFR homozygotes than in the patients with a normal genotype,
      significantly lower in the treated than in the untreated homozygotes, and
      significantly higher in the untreated homozygotes than in the untreated subgroup
      with a normal genotype. The homocysteine level was also significantly lower in
      the patients who underwent convective haemodialysis than in those who received
      standard bicarbonate dialysis. CONCLUSIONS: A drug containing low concentrations
      of folinic acid combined with vitamin B(12) using an intermittent intravenous
      regimen is effective in reducing the homocysteine plasma concentration in uraemic
      patients. The homocysteine levels seem also to depend on genotype and dialysis
      modality.

PMID- 11509803
TI  - Induction of transcription factor AP-2 by cytokines and prostaglandins in
      cultured mesangial cells.
AB  - BACKGROUND/AIMS: Activator protein-2 (AP-2) is an important transcription factor
      for activation of growth- and inflammatory-associated genes. To detect AP-2 in
      the mesangium, the expression level of AP-2 was examined in cultured mesangial
      cells in response to various cytokines and prostaglandins. The level was also
      observed in kidney tissue samples obtained from patients with proteinuria and
      from a rat nephrosis model. METHODS: AP-2 was immunohistochemically detected with
      a specific antibody. The expression level was analyzed by immunoblotting. Human
      tissue samples were obtained from patients with proteinuria. Kidney samples were
      also obtained from rats with puromycin aminonucleoside-induced nephrosis.
      RESULTS: Pro-inflammatory cytokines, such as IL-6, IL-1 and IL-2, but not TNF
      alpha, induced AP-2 expression in a time- and dose-dependent manner in cultured
      mesangial cells. PGE(2) and PGI(2) also induced AP-2 expression, while PGF(2
      alpha) failed to induce this protein. High expression levels of AP-2 were
      observed in different cell types including mesangial cells of kidney samples from
      patients with proteinuria. Similar results were obtained from the rat nephrosis
      model. CONCLUSION: These findings demonstrate that the primary cytokines induce
      AP-2 protein in mesangial cells. AP-2 may act as a transcription factor to
      produce additional cytokines and growth-associated gene products, suggesting an
      important role for AP-2 for the function of mesangial cells in glomerular
      disorders.

PMID- 11509804
TI  - Two enlarged kidneys: a manifestation of Erdheim-Chester disease.
AB  - Erdheim-Chester disease is a rare form of non-Langerhans' cell histiocytosis.
      This disorder is characterized by a bone involvement and several extraskeletal
      manifestations. We describe the case of a patient with a pleural and pericardial
      effusion leading to tamponade. Pathological examination of pericardium and
      mediastinal adenopathy was normal. The abdominal computed tomography scan showed
      two enlarged kidneys suggestive of Erdheim-Chester disease. Bone scan
      scintigraphy demonstrated symmetrical increased labeling of the long bones. The
      biopsy of perirenal soft tissue confirmed the diagnosis of Erdheim-Chester
      disease.

PMID- 11509805
TI  - IgA nephropathy and pulmonary hemorrhage in an adult.
AB  - IgA nephropathy is the most common glomerular disease worldwide, but is generally
      renal limited or associated with a rash. Pulmonary hemorrhage has been very
      uncommonly associated with IgA nephropathy, although it is frequently seen in
      other glomerulonephritides. We describe a well-proven case of IgA nephropathy
      associated with pulmonary hemorrhage, in which immunosuppressive medication was
      administered. We also review the literature to make a case for immunosuppression
      in these rare patients.

PMID- 11509806
TI  - The effect of estrogen on renal phosphorus handling in the rat.
AB  - BACKGROUND/AIMS: Phosphorus reabsorption in the kidney is regulated by
      parathyroid action on the sodium phosphorus cotransporter (Na-Pi cotransporter).
      There is some evidence that estrogen may also regulate renal phosphorus handling
      but it is not known if this is an effect of estrogen on filtered phosphorus load.
      METHODS: This study examined the effect of estrogen on renal phosphorus handling
      during infusion with calcium or EDTA. Six month old Sprague Dawley rats were
      bilaterally oophorectomized (OOX) or underwent a sham operation under ether
      anaesthesia 6 weeks before undergoing infusion with calcium chloride or EDTA. A
      second study examined renal phosphorus handling after estrogen replacement in the
      OOX rat injected with 20 microg estradiol valerate, or vehicle alone, prior to
      calcium infusion. RESULTS: A comparison of filtered phosphorus load with renal
      phosphorus excretion indicated that the estrogen replete rat had a higher renal
      excretion of phosphorus when infused with both calcium (p = 0.004) and EDTA (p =
      0.037) at all filtered phosphorus loads. A similar analysis in calcium infused,
      estrogen replaced, OOX rats indicated an effect of estrogen to increase renal
      phosphorus excretion (p = 0.007) at all filtered phosphorus loads. OOX resulted
      in a mild metabolic alkalosis, an effect not reversed by estrogen administration,
      that was not related to renal phosphorus excretion. OOX decreased renal sodium
      excretion and uncoupled the relation between renal phosphorus and sodium
      excretion, an effect reversed by estrogen replacement. CONCLUSION: Ovarian
      hormone deficiency in the rat results in a decrease in renal phosphorus
      excretion. This finding is comparable to effects of the menopause and hormone
      replacement therapy in postmenopausal women.

PMID- 11509807
TI  - Low-protein diet suppresses serum insulin-like growth factor-1 and decelerates
      the progression of growth hormone-induced glomerulosclerosis.
AB  - A low-protein (LP) diet has been associated with amelioration of renal function
      in glomerulosclerosis (GS). However, the mechanisms involved are still unclear.
      We have used a mouse transgenic for bovine growth hormone (GH), which develops
      progressive GS and exhibits consistently elevated levels of circulating GH and
      insulin-like growth factor (IGF)-1, to study the effect of dietary protein
      restriction. LP (6% protein) and normal-protein (NP, 20% protein) diets were
      maintained for 30 weeks in mice with established GS of mild/moderate degree. The
      degree of GS was markedly attenuated in LP compared to NP mice. Quantitative
      analysis revealed a significantly lower GS index (1.4 +/- 0.9 in LP vs. 2.8 +/-
      0.8 in NP) and glomerular volume (0.8 x 10(6) +/- 0.1 x 10(6) microm(3) in LP vs.
      1.2 x 10(6) +/- 0.1 x 10(6) microm(3) in NP) in mice with restricted protein
      intake. These morphologic changes were accompanied by a significant reduction in
      renal expression of alpha(1) type-IV collagen (2.4-fold) and tenascin (1.4-fold)
      in LP mice. Serum IGF-1 decreased by 40% and showed a significant correlation
      with alpha(1) type-IV collagen expression with the LP diet. The present finding
      supports the use of the LP diet to decelerate the progression of GS and
      furthermore suggests that one of the mechanisms involved in this process is the
      GH/IGF-1 regulation by protein intake.

PMID- 11509808
TI  - Determination of xanthopterin in patients with renal insufficiency.

PMID- 11509809
TI  - Plasma cyclic guanosine monophosphate reflecting the severity of persistent
      pulmonary hypertension of the newborn.
AB  - The aim of the study was to examine the relationship between the plasma
      concentration of cyclic guanosine monophosphate (cGMP) and pulmonary pressure and
      hypoxia defined by oxygenation index (OI) in newborn infants with severe
      persistent pulmonary hypertension (PPHN) on inhaled nitric oxide (NO). In this
      prospective study, 18 newborn infants having Doppler ultrasound-diagnosed PPHN
      and treated with NO were investigated. The ratio of pulmonary artery to systemic
      artery pressure (PAP/SAP) and OI was assessed before treatment and at 0.5, 1, 12,
      and 24 h from the beginning of NO. At these time points, plasma concentrations of
      cGMP could be determined in 11 patients. The association of birth asphyxia as
      assessed by Apgar 1 min and 5 min and plasma cGMP before the NO treatment was
      examined. The initial median plasma concentration of cGMP was 37.3 pmol/ml (IQR
      13.3-79.6). After the start of NO, cGMP increased significantly within 60 min (p
      = 0.003) and peaked at 12 h. Initial plasma cGMP was associated with Apgar score
      (1 and 5 min). OI decreased within 30 min of NO and PAP/SAP within 60 min.
      Persistent high PAP/SAP after 1 h of NO was associated with low cGMP
      concentration (r = 0.70, p = 0.02). We conclude that a significant increase in
      plasma cGMP is already evident after 60 min of NO therapy. This effect is
      accompanied by changes in oxygenation index and in pulmonary artery pressure.
      Initial plasma concentrations of cGMP were associated with hypoxia assessed as
      Apgar score.

PMID- 11509810
TI  - Relation between birth weight and placenta weight.
AB  - With the goal to establish a model that relates birth weight to placenta weight,
      adjusted for the most documented predictors of birth weight, 300 live newborns
      were studied, all were products of single gestation. Inclusion criteria were
      newborns with gestational age of 37 weeks or older according to the date of last
      menstruation, whose mothers did not have diabetes mellitus, high blood pressure,
      pre-eclampsia, or eclampsia. The weight of the newborn was identified from the
      anthropometry data collected by previously trained nursing personnel in each of
      the participating hospitals. Immediately after delivery, the placenta was
      weighed. Multiple linear regression was used to see the effect of placenta weight
      and each variable on birth weight. The mean of birth weight was 3,369 g with a
      standard deviation (SD) of 445 g. Placenta weight had a mean of 537 g (SD: 96 g).
      The relation between the weight of the placenta and the birth weight was
      significant, and we found that for each gram increase in placenta weight, birth
      weight is increased by 1.98 g (SE = 0.25, p < 0.01) and this relation is not
      linear, since the quadratic term is significant. Placenta weight has a nonlinear
      relation to the birth weight and is an important predictor of birth weight.
      Together with the gestational age and the maternal age and size, it explains 32%
      of the variability of birth weight. Placenta weight can be a 'sentinel' indicator
      of nutritional and/or environmental problems.

PMID- 11509811
TI  - Cord blood levels of interleukin-6 and interleukin-8 for the immediate diagnosis
      of early-onset infection in premature infants.
AB  - BACKGROUND: Cytokine plasma levels are suggested to be sensitive indicators of
      neonatal sepsis, but conventional assays are time consuming. This study aimed at
      evaluating the significance of cord blood levels of interleukin (IL)-6 and IL-8
      determined by a fully automated random access assay within 90 min of admission to
      predict systemic bacterial infection. PATIENTS AND METHODS: Cord blood levels of
      IL-6 and IL-8 were determined in 71 mature and 100 premature infants by a
      chemiluminescence assay (Immulite). Patients were divided into four groups
      according to a clinical and laboratory scoring system. Group A: documented early
      onset infection; group B: infection possible; group C: infection unlikely, and
      group D: healthy newborns. RESULTS: Median IL-6 levels in the subgroup of
      premature newborns were as follows: group A, 1,920 pg/ml (5-95% confidence
      interval 308-4,660 pg/ml); group B, 50 (15-102) pg/ml; group C, 21 (12-71) pg/ml,
      and group D, 8 (6-11) pg/ml. For IL-8, median levels for groups A-D were 289 (226
      514) pg/ml, 87 (40-107) pg/ml, 44 (33-98) pg/ml and 21 (16-25) pg/ml,
      respectively. The difference between group A and the other groups was highly
      significant (IL-6 p < 0.0001, IL-8 p < 0.001). At a cut-off of 80 pg/ml, the
      sensitivity of IL-6 for the diagnosis of sepsis was 96% (specificity 95%). For IL
      8 (cut-off 90 pg/ml), the sensitivity was 87% (specificity 94%). CONCLUSION: In
      premature infants, the diagnosis of an early-onset infection can be established
      or ruled out with a high level of confidence by measuring IL-6 or IL-8 levels
      from cord blood using a random access chemiluminescence assay.

PMID- 11509812
TI  - Inhibition of macrophage proinflammatory cytokine expression by steroids and
      recombinant IL-10.
AB  - Chronic lung disease (CLD) of prematurity is a prolonged respiratory failure in
      very-low-birth-weight neonates. Proinflammatory cytokines have been implicated in
      the development of CLD. Steroids have been shown to produce some improvement in
      neonates with this disease. The purpose of this study was to evaluate the
      downregulation of these proinflammatory cytokines by dexamethasone, budesonide
      and recombinant IL-10 (rIL-10) in order to elucidate the mechanism of the
      clinical benefit of steroids in babies. Our results showed that dexamethasone,
      budesonide and rIL-10 significantly inhibited both IL-6 and TNF-alpha production
      in the THP-1 cell line stimulated by lipopolysaccharide and Ureaplasma
      urealyticum antigen. Similar effects were found in macrophages from
      tracheobronchial aspirate fluid from newborn infants. In the rat alveolar
      macrophage cell line, steroids inhibited IL-6 and TNF-alpha production, while rat
      rIL-10 did not significantly decrease production. In conclusion, steroids and
      human rIL-10 were able to downregulate proinflammatory cytokine production, which
      may explain the beneficial effect of steroids and suggests that rIL-10 could be
      tried as an anti-inflammatory agent in neonates with a high risk of CLD.

PMID- 11509813
TI  - Granulocyte colony-stimulating factor, granulocyte macrophage colony-stimulating
      factor and neutrophils in the bronchoalveolar lavage fluid of premature infants
      with respiratory distress syndrome.
AB  - BACKGROUND: Granulocyte colony-stimulating factor (G-CSF) and granulocyte
      macrophage colony-stimulating factor (GM-CSF) promote clonal maturation of
      neutrophil and macrophage progenitors and increase functional activities of
      mature cells. The number and activity of neutrophils and macrophages in the lung
      affect healing and remodeling following respiratory distress syndrome (RDS).
      QUESTIONS OF THE STUDY: (1) Are G-CSF and GM-CSF present in the airways of
      preterm neonates with RDS? (2) Do airway G-CSF and GM-CSF concentrations
      correlate with neutrophil and macrophage number in the bronchoalveolar lavage
      (BAL) fluid? (3) Are alveolar macrophages a source of airway G-CSF and GM-CSF?
      (4) Is in vitro expression of G-CSF and GM-CSF by airway macrophages modified by
      dexamethasone, endotoxin, or hyperoxia? METHODS: Eighteen preterm neonates with
      RDS requiring mechanical ventilation within the first 24 h of life underwent BAL
      on days 1, 3, 6, 10, 12, 15, 20, and 28 if still intubated. BAL G-CSF and GM-CSF
      concentrations were measured by ELISA, and neutrophils and macrophages were
      counted. Alveolar macrophages were cultured, and G-CSF and GM-CSF expression
      measured in the presence and absence of dexamethasone, endotoxin, and hyperoxia.
      RESULTS: G-CSF and GM-CSF were present in the BAL of intubated preterm neonates.
      In infants who did not develop chronic lung disease (CLD) (n = 5), G-CSF and GM
      CSF concentrations were highest in the first days of life, falling thereafter,
      while in those who did develop CLD (n = 13) these concentrations increased over
      time. Neutrophil concentrations in BAL fluid followed a similar pattern.
      Macrophages from BAL were identified as a source of G-CSF and GM-CSF mRNA and
      protein. G-CSF and GM-CSF expression by these macrophages was increased by
      endotoxin, decreased by dexamethasone, and unchanged by hyperoxia. CONCLUSIONS: G
      CSF and GM-CSF are present in neonatal BAL, and may contribute significantly to
      the accumulation of alveolar neutrophils.

PMID- 11509814
TI  - Once-a-day individualized amikacin dosing for suspected infection at birth based
      on population pharmacokinetic models.
AB  - Amikacin is widely used in the treatment of suspected or confirmed neonatal
      infections. However, dosage regimens are not well defined in this group of
      patients because of a wide inter-individual pharmacokinetic variability. An
      individualized goal-oriented amikacin dosage design was applied using population
      pharmacokinetic data. A dosing chart was developed for neonates during the first
      2 days of life, by using population pharmacokinetic parameter values and USCPACK
      software. This dosing chart based on gestational age (GA) and body weight gives a
      once-a-day amikacin dosage regimen involving an injection every 24 h. Validation
      was performed in 57 neonates less than 2 days old, divided into three GA groups
      and prospectively treated using the dosing chart. Target peak serum levels of
      amikacin were obtained in 62-80% of patients after the first dose and in 80-100%
      after the second dose, and trough concentrations were obtained in 100%. This
      study has confirmed the need for individualization of amikacin dosage regimens in
      neonates.

PMID- 11509815
TI  - Prescription of home oxygen therapy to infants in Germany.
AB  - There is no consensus on home oxygen therapy in infancy. We hypothesised that
      this might lead to considerable variability in the practice of prescribing home
      oxygen to infants. To assess this variability, a structured questionnaire was
      sent to all departments of Paediatrics in Germany (n = 380). Response rate was
      92% (n = 349). Indications were mostly (86%) based on long-term recordings of
      pulse oximeter saturation (S(P)O(2)). There was, however, a wide range (85-94%,
      mean 90%) of S(P)O(2)-values below which oxygen therapy was considered indicated.
      Hospitals more experienced with this therapy tended to prescribe oxygen at
      S(P)O(2) values closer to the physiological range. Similarly, S(P)O(2) values
      aimed for during therapy ranged from 86 to 100%, with hospitals prescribing home
      oxygen more frequently aiming for higher values. These differences would argue
      for concentrating home oxygen therapy to centers with the largest experience.

PMID- 11509816
TI  - Prenatal ethanol consumption increases retinol and cellular retinol-binding
      protein expression in the rat fetal snout.
AB  - Fetal exposure to ethanol disrupts normal craniofacial development, resulting in
      characteristic features of fetal alcohol syndrome (FAS). One mechanism that could
      result in some anomalies of this syndrome is through ethanol disrupting the
      regulatory role played by vitamin A in fetal development, thereby inducing
      morphological alterations which manifest as FAS. This work begins to explore a
      possible interaction of ethanol with vitamin A in craniofacial development.
      Retinoid levels and the expression of cellular retinol-binding protein (CRBP) and
      retinoic acid receptor (RAR) mRNA were determined in snouts of 20-day fetuses
      exposed to ethanol throughout gestation, compared to controls. Snout retinol and
      retinyl palmitate levels were elevated in fetuses of ethanol-treated rats, but
      retinoic acid levels were unaffected. The expression of CRBP mRNA, as determined
      by Northern analysis, was greater in snouts of fetuses exposed to ethanol, but
      there was no change in RAR alpha, beta, gamma or retinoid X receptor beta mRNA.
      These results demonstrate that prenatal ethanol consumption can alter certain
      markers of vitamin A metabolism and function in the fetal snout.

PMID- 11509817
TI  - Auditory brainstem response and unbound bilirubin in jaundiced (jj) Gunn rat
      pups.
AB  - The role of plasma bilirubin-albumin binding in the pathogenesis of kernicterus
      in human newborns is controversial. Kernicterus in the jaundiced (jj) Gunn rat
      pup, an animal model for kernicterus, prolongs interwave intervals and decreases
      wave amplitude in the auditory brainstem response (ABR). Plasma total bilirubin
      concentration (TBC), albumin concentration, and unbound bilirubin concentration
      (UBC), a measure of bilirubin-albumin binding, were measured in 16-day-old jj
      Gunn rat pups (n = 21) and compared with ABR wave latencies, interwave intervals,
      and wave amplitudes by linear correlation. The UBC, but not the TBC or
      TBC/albumin ratio, correlated positively and significantly with ABR I-II and I
      III interwave intervals (r = 0.55, p = 0.009, and r = 0.60, p = 0.004,
      respectively). The UBC, but not the TBC or TBC/albumin ratio, predicts bilirubin
      toxicity, as measured by bilirubin-induced ABR changes in jj Gunn rat pups.

PMID- 11509818
TI  - Prophylactic effects of recombinant human superoxide dismutase in neonatal lung
      injury induced by the intratracheal instillation of endotoxin in piglets.
AB  - The efficacy of prophylactic endotracheal administration of superoxide dismutase
      (SOD) was assessed in an animal model of acute lung injury induced by
      intratracheal endotoxin in neonatal piglets. Twenty-one anesthetized piglets were
      studied and underwent mechanical ventilation. The animals received recombinant
      human SOD (5 or 20 mg/kg intratracheally) 10 min before induction of acute lung
      injury with intratracheal endotoxin (20 mg/kg). The PaO(2) values of the SOD
      treated group remained higher than that of the control group until the end of the
      experiment. In contrast, the PaCO(2) values remained lower. Lung compliance
      remained higher. Thiobarbituric acid-reactive substances and albumin levels in
      the broncho-alveolar lavage fluid were more significantly increased in controls.
      Histologic examination showed that the degrees of atelectasis and edema in the
      SOD treatment group were milder than those of the control group. Thus, the
      present findings suggest that prophylactic treatment with SOD may be, at least in
      part, effective for alleviating acute lung injury caused by endotoxins.

PMID- 11509819
TI  - Pre- and postnatal tissue selenium of the rat in the growing state.
AB  - The aim of this study is to quantify the selenium (Se) content (in microg/g)
      during different gestational periods in rat fetal tissues, and to follow up the
      changes in the Se content of the placenta, fetal head, liver and lung during
      gestation and postpartum periods. Locally reared virgin female Wistar rats were
      mated. Pregnant rats were sacrificed on days 15, 18 and 21 of pregnancy. Newborn
      pups at the age of 3 days and rats at the age of 1 month were also investigated.
      There was a gradual increase in placental and whole head Se content as gestation
      proceeded compared to day 15; however, the differences between the groups were
      not statistically significant. The liver Se content at day 18 of gestation was
      significantly higher than at day 21 of gestation and in rats at 3 days of age,
      but lower than the Se content of the liver of rats at the age of 1 month and the
      differences were statistically significant. The lung Se content was higher at day
      18 of gestation than at day 21 and in the 3-day-old rats, and all differences
      between all groups were statistically significant except when the lung Se content
      at day 18 is compared to that of 1-month-old animals. The continuous increase in
      the Se content of the placental tissues and the whole head, although not
      significant statistically, may indicate that the fetus relies heavily on its
      supply of Se from the maternal blood and in part on the supply of thyroid
      hormones which are important for brain development, as evidence exists that T(4)
      and T(3) are present in the fetal brain in early fetal life before the onset of
      fetal thyroid function. The higher content of Se on day 18 and its decline on day
      21 of gestation in the liver may imply that it is stored and being utilized
      partly in other tissues for other functions and particularly for thyroid hormone
      synthesis, metabolism and functions.

PMID- 11509820
TI  - Antenatal terbutaline administration decreases the lung hyaluronan concentration
      in preterm rabbit pups.
AB  - OBJECTIVE: To determine whether antenatal exposure to terbutaline alters the lung
      hyaluronan concentration or lung water content at birth in preterm rabbit pups.
      STUDY DESIGN: Rabbit dams (n = 18) with timed pregnancies were injected with 30
      microg terbutaline or saline (controls) one day before delivery at 27-29 days of
      gestation. Pups were killed immediately after delivery. Lung water content and
      hyaluronan concentrations were determined. RESULTS: Pups exposed antenatally to
      terbutaline had lower mean lung hyaluronan concentrations than control pups. Lung
      hyaluronan/dry lung weight was significantly lower in pups delivered at 28 (p =
      0.034) or 29 days (p < 0.001), while lung hyaluronan/wet lung weight was
      significantly lower at all three gestational ages. CONCLUSION: Antenatal exposure
      to terbutaline lowers the lung hyaluronan concentration at birth in preterm (27
      29 days) rabbit pups without altering the lung water content.

PMID- 11509821
TI  - Sensory brain areas in mesopelagic fishes.
AB  - Four areas of the brain that receive primary projections from chemical senses
      ([1] olfactory bulb, [2] facial and vagal lobes), the eye ([3] optic tectum), and
      somato- and mechanosensory systems such as the lateral line, vestibular and
      auditory systems ([4] trigeminal and octavolateral regions) have been studied and
      relative size differences used to deduce the sensory specializations of 67
      species of mesopelagic fishes. One type of analysis used the average relative
      volumes of brain areas and identified 'specialists' with only one brain area
      above-average (36%), species 'dominated' by two sensory brain regions (49%), and
      generalists (15%), with three areas above-average. In addition, a cluster
      analysis was performed that separated 49 species which were mostly visually
      oriented from 18 non-visual species, among which 16 were characterized by an
      association of above-average trigeminal/octavolateral and gustatory areas, and a
      single species with a dominant olfactory bulb. The results support the idea that
      these species occupy a rich sensory environment for which the absence of sunlight
      is compensated by chemical and mechanosensory stimuli as well as by
      bioluminescent signals. This has lead to the development of specializations for
      the perception of single stimulus-modes, most notably for the visual system, as
      well as for combinations of various receptors and central processing areas, with
      a preference for associating either the chemical senses, including the olfactory
      and facial/vagal systems, or the trigeminal/octavolateral systems.

PMID- 11509822
TI  - Brainstem acoustic areas in the marine catfish, Arius felis.
AB  - The marine catfish Arius felis produces low frequency sounds for communication
      and obstacle detection. It was hypothesized that the utriculus of the inner ear
      might play an important role in these behaviors. In the current study, brainstem
      acoustic areas were studied to reveal possible neuroanatomical specializations in
      utricular processing areas. The first-order octaval nuclei in Arius were
      identical in number, anatomical characteristics, and organization of saccular,
      lagenar, and utricular inputs to previous reports of these features in Ictalurus,
      a closely related species of catfish that does not exhibit the specialized
      acoustic behaviors present in Arius. Similarly, injections of neural tracer in
      the acoustic midbrain (nucleus centralis) of Arius revealed afferent and
      retrograde pathways almost identical to those previously reported in Ictalurus.
      It is suggested that areas within the primary and higher-order octaval nuclei
      that utilize utricular input in acoustic processing are likely identical in Arius
      and Ictalurus. Two sets of higher-order connections in Arius differ from those in
      Ictalurus. First, Arius apparently lacks the direct input from the anterior
      octaval nucleus to nucleus centralis reported in Ictalurus. Second, in Arius
      nucleus centralis projects bilaterally to a strip of neurons positioned ventral
      to the ventral boundary of the torus semicircularis. This projection is
      apparently absent in Ictalurus and in the related species Carassius (goldfish),
      but has been previously reported in Porichthyes, a sound-producing species
      belonging to a different teleost taxon.

PMID- 11509823
TI  - Distribution of neuronal melanocortins in the spadefoot toad Spea multiplicata
      and effects of stress.
AB  - We examined the effects of an acute stressor on regional alpha-melanocyte
      stimulating hormone (alphaMSH) content in the New Mexican spadefoot toad, Spea
      multiplicata. We first used immunocytochemistry along with radioimmunoassay (RIA)
      to examine the distribution of pro-opiomelanocortin (POMC) neurons in the brain
      of Spea. Neurons immunoreactive for alphaMSH, beta-endorphin, and corticotropin
      were observed in the preoptic nucleus and ventral infundibulum of the
      hypothalamus. Ascending immunoreactive fibers projected to the olfactory nucleus,
      nucleus accumbens, and striatum. Numerous immunoreactive fibers were also
      observed in the hypothalamus. The thalamus/hypothalamus (T/HT) contained the
      greatest concentrations of alphaMSH as determined by RIA followed by the preoptic
      area (PO). Levels in the telencephalon, brain stem, and optic tectum (OT) were 14
      23 times lower than in the T/HT. Exposure to a brief stressor elevated alphaMSH
      levels in the PO and OT. We conclude that Spea possesses two distinct POMC
      neuronal cell groups, one located in the anterior preoptic area and one located
      in the ventral infundibulum. Ascending projections to the basal ganglia might
      play an indirect role in tectal regulation and the control of prey-catching
      behavior. Exposure to an acute stressor alters brain alphaMSH content in Spea,
      although there are regional and temporal differences in the response pattern
      compared to Bufo. These findings are consistent with the notion that neuronal
      melanocortins influence how frogs and toads gather information about their
      environment during stress.

PMID- 11509824
TI  - Comparison of brain volumes between single and multiple foundresses in the paper
      wasp Polistes dominulus.
AB  - Queens of the paper wasp Polistes dominulus have the option to found nests in
      spring alone or together with other queens. In the latter case a dominance
      hierarchy is established among the cofoundresses with the dominant wasp getting
      the major share of the reproductive output of the nest. The different
      reproductive strategies of an individual wasp will necessitate different
      behaviors. We measured the volumes of brain structures as a potential indicator
      of differential use and elaboration of a number of brain structures. We found a
      significant increase in the volume of the antennal lobe in members of multiple
      foundress associations in comparison to single foundresses. The volume of the
      collar, a substructure of the calyx of the mushroom body, was also significantly
      larger, especially in the dominant queen of a foundress association. No
      significant differences between dominant or subordinate wasps in regard to volume
      of the measured brain substructures were found.

PMID- 11509825
TI  - Reactive oxygen species as intracellular messengers during cell growth and
      differentiation.
AB  - Reactive oxygen species (ROS) are generated following ligand-receptor
      interactions and function as specific second messengers in signaling cascades
      involved in cell proliferation and differentiation. Although ROS are generated
      intracellularly by several sources, including mitochondria, the primary sources
      of ROS involved in receptor-mediated signaling cascades are plasma membrane
      oxidases, preferentially NADPH oxidases, with a rapid kinetics of activation and
      inactivation. This allows a tight up- and downregulation of intracellular ROS
      levels within the short time required for the transduction of signals from the
      plasma membrane to the cell nucleus. The mode of action of ROS may involve direct
      interaction with specific receptors, and/or redox-activation of members of
      signaling pathways such as protein kinases, protein phosphatases, and
      transcription factors. Furthermore, ROS act in concert with intracellular Ca(2+)
      in signaling pathways which regulate the balance of cell proliferation versus
      cell cycle arrest and cell death. The delicate intracellular interplay between
      oxidizing and reducing equivalents allows ROS to function as second messengers in
      the control of cell proliferation and differentiation.

PMID- 11509826
TI  - Hypoxia-effects on Ca(i)-signaling and ion transport activity of lung alveolar
      epithelial cells.
AB  - In excitatory cells specific responses upon changes in PO(2) are mediated by
      changes in intracellular Ca (Ca(i)). We wanted to know whether ion transport of
      lung alveolar epithelial cells is regulated by Ca(i) and whether Ca(i) and Ca(i) 
      signaling are affected by hypoxia in a way that might explain hypoxic transport
      inhibition (Mairbaurl et al. AJP 273: L797, 1997). The activity of transport
      (Na/K-pump, Na/K/2Cl-cotransport) was measured as unidirectional (86)Rb-uptake
      after A549 cells were exposed to hypoxia (3% O(2)). Ca(i) of primary cultured rat
      alveolar type II cells was measured by fura-2 epifluorescence. Depletion of Ca(i)
      by extracellular chelators in presence of ionomycin or with thapsigargin as well
      as PKC inhibition decreases (86)Rb-uptake of normoxic and hypoxic A549 cells,
      whereas an increased Ca(i) activates transport. Neither immediate nor prolonged
      exposure to hypoxia changes Ca(i) significantly. The increase in Ca(i) upon
      stimulation with ATP, which is caused mainly by release from intracellular
      stores, is smaller in hypoxia than in normoxia. These results indicate that ion
      transport of alveolar epithelial cells is modulated by Ca(i). A change in Ca(i)
      does not mediate hypoxic transport inhibition. The decreased Ca(i) transients in
      hypoxia might indicate a blunted response to extracellular stimuli.

PMID- 11509827
TI  - Cytosolic Ca(2+) levels and DNA synthesis of human umbilical vein endothelial
      cell cultures are unresponsive to thrombopoietin treatment.
AB  - The hormone thrombopoietin (TPO) induces proliferation of megakaryocytic
      progenitors and augments agonist-induced mobilization of Ca(2+) in platelets.
      Because the action of TPO is not restricted to the megakaryocytic lineage, we
      studied the occurrence of TPO receptor mRNA and protein, and effects of TPO on
      cytosolic Ca(2+) levels and DNA synthesis in human umbilical vein endothelial
      cell cultures (HUVECs). Polymerase chain reaction following reverse transcription
      (RT-PCR) of total mRNA revealed that TPO receptor (MPL) mRNA was expressed only
      at low level in our samples. TPO receptor protein was not detectable in HUVEC
      lysates investigated by immunoprecipitation and immunoblotting. In contrast to
      vascular endothelial growth factor (VEGF), TPO did neither alter fura2
      fluorescence as a measure of cytosolic Ca(2+) levels nor increase 5-bromo-2'
      deoxyuridine incorporation into DNA of HUVECs. In conclusion, our data
      demonstrate that HUVECs are neither structurally nor functionally responsive to
      TPO.

PMID- 11509828
TI  - Urinary excretion of aquaporin-2 water channel during pregnancy.
AB  - BACKGROUND: In healthy primiparas the total body water content increases by about
      8 liters within the last trimester, with a consequent reduction in plasma
      arginine-vasopressin (AVP) levels. The aim of the present study was to
      investigate the effect of normal pregnancy on urinary excretion of AQP2, a
      vasopressin sensitive water channel. METHODS: Forty-five healthy pregnant
      primiparas (specify mean age and range) with a physiological single-fetus
      pregnancy were studied during weeks 12, 24 and 36 of pregnancy and then for 3 to
      5 days postpartum. The control group consisted of 14 age-matched women in the
      early follicular phase of the menstrual cycle (day 5 or 6). The behavior of
      plasma AVP, ANP, oxytocin, urinary 6-keto-PGF1alpha (a metabolite of
      prostacyclin) and urinary AQP-2 excretion were evaluated in all subjects.
      RESULTS: Plasma ANP and oxytocin, and urinary AQP-2 and 6kPGF1alpha excretion
      increased during all three trimesters, with the highest peaks at the 36(th) week.
      In the postpartum period, these values markedly decreased. No statistically
      significant changes were found in plasma AVP levels throughout the study period.
      CONCLUSIONS: Our findings suggest that a non-AVP factor present in pregnancy
      plays a role in the control of the excretion of AQP-2 water channels.

PMID- 11509829
TI  - Effects of the serine/threonine kinase SGK1 on the epithelial Na(+) channel
      (ENaC) and CFTR: implications for cystic fibrosis.
AB  - Cystic fibrosis (CF) is characterized by impaired Cl(-) secretion and increased
      Na(+) reabsorption in several tissues including respiratory epithelium. Many CFTR
      mutations have been identified over the past years. However, only a poor
      correlation between the genotype and lung phenotype was found suggesting
      additional factors influencing the phenotype and course of the disease. The
      serine/threonine kinase SGK1 has recently been shown to stimulate the activity of
      the epithelial Na(+) channel ENaC. A variety of stimuli such as aldosterone, cell
      shrinkage, insulin or TGF-beta1 stimulate transcription and activate the SGK1
      kinase. Here we further examined the effects of SGK1 on ENaC and CFTR which have
      mutual interactions and we analyzed sgk1 mRNA abundance in lung tissue from CF
      patients. Coexpression of CFTR and h-SGK1 in Xenopus oocytes increased ENaC
      currents as previously described. In addition CFTR mediated currents were also
      stimulated. h-SGK1 accelerated the expression of the amiloride sensitive Na(+)-
      current in Xenopus oocytes paralleled by increased ENaC-protein abundance in the
      oocyte membrane, an effect which was reversed by a h-SGK1(K127R) mutation lacking
      the ATP-binding site. The cation selectivity or Na(+) affinity were not affected.
      However, coexpression of h-SGK1 with ENaC altered the sensitivity of the Na(+)
      channel to the inhibitors amiloride and triamterene. The inhibitory effect of
      CFTR expression on ENaC current was not affected by coexpression of h-SGK1 in
      Xenopus oocytes. Lung tissue from CF patients strongly expressed the
      serine/threonine kinase h-sgk1 which was not the case for non-CF lung tissue.
      Loss of CFTR function itself in a CF lung epithelial cell line did not increase
      SGK1 expression. In summary, enhanced expression of h-SGK1 in epithelial cells of
      CF-lung tissue may be a novel pathophysiological factor contributing to increased
      Na(+) channel activity and thus to increased Na(+) transport in CF.

PMID- 11509831
TI  - Postnatal expression of alpha-synuclein protein in the rodent substantia nigra
      and striatum.
AB  - A primary goal of our research is to elucidate the mechanisms involved in
      neuroplasticity of the basal ganglia in both development and in response to
      injury. One means to this aim is through the analysis of the ontological profile
      of proteins in the basal ganglia and to correlate their pattern of expression
      with morphological development. One protein thought to be important in
      neuroplasticity is alpha-synuclein. The purpose of this study was to characterize
      and compare the pattern of expression of alpha-synuclein protein using
      immunocytochemistry in the substantia nigra and striatum of the rodent in early
      postnatal and adult life. Our results demonstrate that there is a high level of
      expression of alpha-synuclein protein within cell bodies of the substantia nigra
      pars compacta in the 1st week of postnatal life that decreases both in intensity
      and number of immunoreactive cells between postnatal days 7 and 14. This is in
      contrast to the substantia nigra pars reticulata where alpha-synuclein protein
      expression in the neuropil increases after postnatal day 7. In the striatum,
      expression in early postnatal life is distributed in a mosaic-like fashion and
      becomes more diffuse after postnatal day 14. Our results support the findings of
      others that expression of alpha-synuclein is developmentally regulated and
      suggest that alpha-synuclein may play an important role in establishing the
      function of the basal ganglia. Understanding the role of alpha-synuclein in the
      normal basal ganglia may provide insights into the molecular mechanisms involved
      in neuroplasticity in response to injury.

PMID- 11509830
TI  - Characterisation of the rat SK4/IK1 K(+) channel.
AB  - BACKGROUND AND AIMS: The Ca(2+)-activated K(+) channel rSK4 is the rat homologue
      of the human SK4/IK1 (KCNN4) channel. In colonic mucosa rSK4 plays a key role
      during acetylcholin-induced secretion. This study was aimed to characterize the
      properties of the rat SK4 channel. METHODS: Electrophysiological measurements
      were performed on rSK4 expressing Xenopus laevis oocytes and rat colonic crypts.
      Intracellular Ca(2+) activity was assessed by Oregon Green fluorescence
      measurements. RESULTS: The 10 pS rSK4 expressed in oocytes was Ca(2+)-sensitive
      and inhibited by calmodulin antagonists. 1-ethyl-2-benzimidazolinone (1-EBIO), a
      known activator of SK4/IK1 channels, also activated rSK4. 1-EBIO affected the
      current neither at saturating Ca(2+) activities nor under Ca(2+)-free conditions,
      but increased the Ca(2+) sensitivity of rSK4. rSK4 was strongly activated by
      cytosolic ATP. However, PKA itself, PKA inhibitors and mutation of the PKA
      phosphorylation site (S332A) did not affect channel activity. The PKC activator
      1,2-dioctanoyl-sn-glycerol and the PKC inhibitor bisindolylmaleimide also failed
      to influence rSK4. CONCLUSION: The Ca(2+)-sensitive rSK4 is activated by 1-EBIO
      probably via facilitation of the Ca(2+)-calmodulin-rSK4 interaction. The strong
      ATP-activation of rSK4 is likely to be caused by phosphorylation via a yet
      unknown kinase and might involve additional subunits.

PMID- 11509832
TI  - Maternal choline availability alters the localization of p15Ink4B and p27Kip1
      cyclin-dependent kinase inhibitors in the developing fetal rat brain hippocampus.
AB  - Previously we have shown that changes in maternal dietary choline are associated
      with permanent behavioral changes in offspring. Importantly, in adult male rats,
      feeding a choline-deficient diet increases the localization of cyclin-dependent
      kinase inhibitors (CDKIs) in the liver, whereas young adult CDKI knockout mice
      (p15Ink4B or p27Kip1) exhibit behavioral abnormalities. Thus, maternal dietary
      choline-CDKI interactions could underlie the changes we observe in fetal
      hippocampal development and cognitive function in offspring. Here, timed-pregnant
      rats on embryonic day E12 were fed the AIN-76 diet with varying levels of dietary
      choline for 6 days, and, on E18, fetal brain sections were collected, and the
      localization of CDKI proteins was studied using immunohistochemistry and an
      unbiased image analysis method. In choline-supplemented animals compared to
      controls, the number of cells with nuclear immunoreactivity for p15Ink4b CDKI
      protein was decreased 2- to 3-fold in neuroepithelial ventricular zones and
      adjacent subventricular zones corresponding to the fimbria, primordial dentate
      gyrus and Ammon's horn regions in the fetal hippocampus. In contrast, maternal
      dietary choline deficiency significantly decreased nuclear p15Ink4b
      immunoreactivity in the neuroepithelial layer of the dentate gyrus. Unlike
      p15Ink4b, the CDKI protein p27Kip1 was observed almost exclusively in the
      cytoplasm, though the protein was distributed throughout the proliferating and
      postmitotic zones in the E18 fetal hippocampus. Maternal dietary choline
      supplementation decreased the cytoplasmic staining intensity for p27Kip1
      throughout the fetal hippocampus compared to control animals. Choline deficiency
      increased the staining intensity of p27Kip1 throughout the hippocampus in
      association with increased expression of MAP-1 and vimentin proteins. These
      results link maternal dietary choline availability to CDKI protein
      immunoreactivity and commitment to differentiation during fetal hippocampal
      development.

PMID- 11509833
TI  - NMR spectroscopic analysis of rat brain development: in vitro proton and carbon
      studies of whole tissue and its phospholipid fraction.
AB  - The developmental patterns of the rat brain at several postnatal time points were
      investigated in Folch (chloroform-methanol) extracts. The chloroform- (lipid
      containing) and water-soluble (cytosolic) fractions of whole-tissue extracts and
      the phospholipid fraction separated from the organic fraction by chromatography
      were analysed by means of high-resolution (1)H and (13)C nuclear magnetic
      resonance (NMR) spectroscopy. Analysis of the cytosolic fraction showed the
      changing patterns of several brain metabolites during postnatal maturation, in
      full agreement with data obtained from perchloric acid extracts. (1)H NMR
      spectroscopy of the phospholipid fraction allowed for quantitative evaluation of
      fatty acid acyl chain length, mean unsaturation and mean polyunsaturation. It was
      found that both mean unsaturation and polyunsaturation are lower in adult brain
      phospholipids than during the first 3 postnatal weeks. (13)C NMR spectroscopy of
      the same fraction showed that the molar percentage of C(18) fatty acids (oleic,
      linoleic, linolenic) in brain phospholipids is similar at all the investigated
      time points. These results indicate that the combination of Folch extraction with
      simple chromatographic procedures and NMR analysis yields useful data to define
      the chemical maturation of the brain.

PMID- 11509834
TI  - The Krox-20 null mutation differentially affects the development of masticatory
      muscles.
AB  - The Krox-20 null mutation results in a loss of rhombomeres 3 and 5, which give
      rise to neurons that are essential to oral motor behaviors. Thus, the Krox-20
      null mutant is an excellent model to investigate the development of oral motor
      circuitry. Our morphological examination of embryonic and neonatal Krox-20 null
      mutants revealed that a significant reduction of anterior digastric and mylohyoid
      muscles, the primary jaw openers, occurs between embryonic days 15 and 19. There
      are no gross morphological alterations in other masticatory muscles. These
      findings demonstrate that Krox-20 expression is critical for the normal
      development of the primary jaw opener musculature and they help explain previous
      studies documenting a reduction in jaw opening in Krox-20 null mutants. Since jaw
      opening is the power stroke of suckling behavior, our data help explain the
      reduction of colostrum/milk ingestion in Krox-20 null mutant neonates.

PMID- 11509835
TI  - Delayed postnatal development of NMDA receptor function in medium-sized neurons
      of the rat striatum.
AB  - During early postnatal development, the N-methyl-D-aspartate (NMDA) subtype of
      glutamate receptor plays a dominant role in excitatory amino acid-mediated
      synaptic transmission in essentially every brain region that has been examined.
      In contrast, we have found that in the rat striatum, NMDA receptor-mediated
      current develops later in the medium-sized neurons (MSNs) than currents mediated
      by activation of non-NMDA receptors. MSNs were identified using infrared video
      microscopy, and voltage-clamped in a slice preparation using the whole-cell patch
      clamp technique. Intrastriatal stimulation was used to evoke excitatory synaptic
      currents from slices in animals ranging in age from postnatal day (PND) 5 to 60.
      Though most cells from animals younger than PND 10 failed to respond to synaptic
      stimulation, postsynaptic responses were occasionally evoked in cells as young as
      PND 5. Synaptic currents from cells between PNDs 5 and 7 had a significant
      contribution due to activation of non- NMDA receptors, as evidenced by
      sensitivity to the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3
      dione and rapidly rising and falling response components. The relative
      contribution of NMDA receptors increased approximately twofold from the first to
      the third postnatal week; no further change was observed through PND 60. At the
      same ages that the NMDA receptors contributed maximally to the synaptic current,
      the decay time constant of the NMDA receptor-mediated current decreased
      significantly. The increasing weight of NMDA receptor-mediated current may
      reflect a change in the number of functional receptors at the synapse since there
      was no apparent change in the voltage dependence of the current. To more
      completely examine receptor function early in postnatal development, NMDA and
      kainate were applied either iontophoretically or in the bath. Iontophoretic
      application of NMDA onto cells obtained from rats between PNDs 3 and 5 only
      occasionally evoked current, provided that the membrane was held at depolarized
      potentials to remove the Mg(2+) block. In contrast, application of kainate
      consistently evoked a response from cells of the same age group. Bath application
      of the same agonists provided similar results. Taken together, the present
      experiments demonstrate that striatal non-NMDA receptor-mediated currents are
      more mature than NMDA receptor-mediated currents early in development.

PMID- 11509836
TI  - Effect of prenatal exposure to diazepam on brain GABA(A) receptor mRNA levels in
      rats examined at late fetal or adult ages.
AB  - This study tested the hypotheses that in utero exposure to diazepam (DZ): (1)
      exerts long-lasting effects on GABA(A) receptor function by altering GABA(A)
      receptor subunit mRNA levels in specific brain regions of adult animals and/or
      (2) alters GABA(A) subunit mRNA expression in exposed fetuses. We assayed levels
      of mRNAs encoding several of the most predominant GABA(A) receptor subunits as
      well as cyclophilin mRNA. Analysis of mRNA levels in the cortex in adults showed
      that only gamma2S mRNA levels varied significantly with prenatal drug exposure,
      an effect unrelated to DZ action to the GABA(A) receptor. Analysis in fetuses
      indicated that mRNA levels varied as a function of both fetal sex and fetal drug
      environment. Irrespective of sex, DZ exposure increased both alpha1 and
      cyclophilin mRNAs in fetal brainstem whereas the mRNA levels of gamma2S were
      increased and decreased, respectively, in the telencephalon and hypothalamus of
      DZ-exposed fetuses.

PMID- 11509837
TI  - Survival effects of pigment epithelium-derived factor expressed by a lentiviral
      vector in rat cerebellar granule cells.
AB  - We have previously shown that pigment epithelium-derived factor (PEDF) acts as a
      survival factor for cerebellar granule cells (CGCs), by blocking apoptotic death,
      and can also protect these cells against glutamate-induced neurotoxicity. In
      preparation for gene therapy studies, pseudotyped HIV-1-based lentiviral vectors
      containing the PEDF gene, as well as either green fluorescent protein or beta
      galactosidase, were prepared. These bicistronic vectors are unique in that they
      express two genes efficiently under one promoter. Primary cell cultures of CGCs
      from postnatal day 8 rats were infected with the vectors encoding PEDF. RT-PCR
      demonstrated expression of mRNA and Western blot analysis confirmed that infected
      CGCs secrete PEDF protein to the medium. Assays for cell survival demonstrated
      that PEDF-infected cells were significantly more protected compared with mock
      infected controls for 6-8 days in culture, as well as against induced apoptosis.
      The PEDF vectors expressing tat (trans-acting transcription factor) provided more
      protection than the tat(-) vectors. These results demonstrate that while the
      lentiviral vectors expressing PEDF are as neuroprotective as the protein itself
      for CGCs, the vectors have the advantage of providing long-lasting expression of
      PEDF protein, which will be more effective in in vivo studies. The present
      results suggest that this system may be useful for gene therapy for
      neurodegenerative disorders.

PMID- 11509838
TI  - Target cells promote the development and functional maturation of neurons derived
      from a sympathetic precursor cell line.
AB  - The role of target interactions in the development and functional maturation of
      peripheral neurons was investigated using an immortalized sympathetic precursor
      cell line. bMAH cells underwent neuronal differentiation in response to
      neurotrophic factors, but maintained an immature neuronal phenotype characterized
      by small cell bodies and continued cell division. Co-culture with cardiac
      myocytes, a target of sympathetic innervation, promoted the appearance of large
      diameter postmitotic bMAH neurons. Analysis of bMAH maturation in the presence
      and absence of co-cultured myocytes indicated that myocyte-derived factors
      promoted the survival of maturing bMAH neurons prior to their acquisition of
      nerve growth factor dependence. Myocyte interactions also promoted the functional
      maturation of bMAH neurons, leading to an increase in the localization of
      synaptic vesicle proteins into neuritic varicosities and the acquisition of
      sympathetic-like intrinsic electrical properties. Like primary sympathetic
      neurons, mature bMAH neurons formed functional connections to cardiac myocytes as
      measured by evoked postsynaptic responses in connected myocytes. The effects of
      myocyte co-culture on developing bMAH neurons could be mimicked by myocyte
      conditioned medium, indicating that cardiac myocytes produce soluble factors that
      promote the appearance of mature neurons. These experiments indicate that targets
      of innervation play a role in directing the development and final maturation of
      peripheral neurons.

PMID- 11509839
TI  - Applying principles of comparative risk analysis to substance abuse-related
      burden.

PMID- 11509840
TI  - A World Health Organization perspective on alcohol and illicit drug use and
      health.
AB  - Alcohol and illicit drug use has a significant impact on global health. Alcohol
      consumption is increasing worldwide, particularly in developing countries and
      countries in transition, leading to an increasing number of health and social
      problems, both acute and chronic. Illicit drug use is also increasing,
      particularly injection drug use, followed by an epidemic spread of HIV and other
      blood-borne infections. Alcohol and illicit drug use are related to key
      determinants of population health and are also an outcome of poor health.
      Globalized marketing and trade, and rapid social changes and development in the
      absence of strong policies and investments in public health have led to an
      increased availability, use and problems related to alcohol and other substance
      use. Public health policies and substantial investments in effective prevention
      and treatment approaches are needed in order to reduce the negative impact of
      alcohol and other drug use at national and global levels.

PMID- 11509841
TI  - Challenges and approaches to estimating mortality attributable to the use of
      selected illicit drugs.
AB  - A number of unique challenges are faced when attempting to estimate mortality
      attributable to illicit drugs. The hidden nature of illicit drug use creates
      difficulties in quantifying the prevalence of such use; identifying adverse
      health effects associated with exposure, and calculating the risk of these
      effects. The use of cohort studies of drug users allows the identification of
      causes of mortality associated with drug use and the determination of the risk of
      these causes. This risk estimate can then be used in conjunction with estimates
      of the prevalence of drug use to extrapolate the burden of mortality. We identify
      a number of such studies and present some solutions to the major challenges faced
      when attempting to estimate the global burden of mortality attributable to
      illicit drug use.

PMID- 11509842
TI  - Relation between average alcohol consumption and disease: an overview.
AB  - OBJECTIVE: To conduct an overview of alcohol-related health consequences and to
      estimate relative risk for chronic consequences and attributable fractions for
      acute consequences. METHODS: Identification of alcohol-related consequences was
      performed by means of reviewing and evaluating large-scale epidemiological
      studies and reviews on alcohol and health, including epidemiological
      contributions to major social cost studies. Relative risks and alcohol
      attributable fractions were drawn from the international literature and risk
      estimates were updated, whenever possible, by means of meta-analytical
      techniques. RESULTS: More than 60 health consequences were identified for which a
      causal link between alcohol consumption and outcome can be assumed. CONCLUSIONS:
      Future research on alcohol-related health consequences should focus on
      standardization of exposure measures and take into consideration both average
      volume of consumption and patterns of drinking.

PMID- 11509843
TI  - Methodological approaches to conducting pooled cross-sectional time series
      analysis: the example of the association between all-cause mortality and per
      capita alcohol consumption for men in 15 European states.
AB  - AIM: To compare different statistical models in order to estimate the association
      of alcohol consumption and total mortality when time series data stem from
      different regions. DATA AND METHODS: Data on per capita consumption in 15
      European countries were combined with standardized mortality rates covering
      different periods between 1950 and 1995. An indicator of region-specific drinking
      patterns was measured without reference to a concrete time point, thus generating
      a hierarchical data structure. Two groups of models were compared: pooled cross
      sectional time series models with different error structures and hierarchical
      linear models (random coefficient models). RESULTS: If historical time is not
      controlled for in cross-sectional models, this might result in estimating a
      negative association between alcohol consumption and total mortality.
      Hierarchical linear models or cross-sectional models controlling for historical
      time, however, resulted in the expected positive association. Only hierarchical
      linear models were able to adequately estimate the moderating effect of drinking
      patterns on the association between alcohol consumption and total mortality.
      CONCLUSION: For pooled cross-sectional time series data, control for the
      potential impact of historical time is of utmost importance. Hierarchical linear
      models constitute a superior alternative to analyze such complex data sets,
      especially as time-independent characteristics of regions can be implemented in
      the model.

PMID- 11509844
TI  - Steps towards constructing a global comparative risk analysis for alcohol
      consumption: determining indicators and empirical weights for patterns of
      drinking, deciding about theoretical minimum, and dealing with different
      consequences.
AB  - In order to conduct a comparative risk analysis for alcohol within the Global
      Burden of Disease Study (GBD 2000), several questions had to be answered. (1)
      What are the appropriate dimensions for alcohol consumption and how can they be
      categorized? The average volume of alcohol and patterns of drinking were selected
      as dimensions. Both dimensions could be looked upon as continuous but were
      categorized for practical purposes. The average volume of drinking was
      categorized into the following categories: abstention; drinking 1 (> 0-19.99 g
      pure alcohol daily for females, > 0-39.99 g for males); drinking 2 (20-39.99 g
      for females, 40-59.99 g for males), and drinking 3 (> or =40 g for females, > or
      =60 g for males). Patterns of drinking were categorized into four levels of
      detrimental impact based on an optimal scaling analysis of key informant ratings.
      (2) What is the theoretical minimum for both dimensions? A pattern of regular
      light drinking (at most 1 drink every day) was selected as theoretical minimum
      for established market economies for all people above age 45. For all other
      regions and age groups, the theoretical minimum was set to zero. Potential
      problems and uncertainties with this selection are discussed. (3) What are the
      health outcomes for alcohol and how do they relate to the dimensions? Overall,
      more than 60 disease conditions were identified as being related to alcohol
      consumption. Most chronic conditions seem to be related to volume only
      (exceptions are coronary heart disease and ischemic stroke), and most acute
      conditions seem to be related to volume and patterns. In addition, using
      methodology based on aggregate data, patterns were relevant for attributing harms
      for men but not women.

PMID- 11509845
TI  - Average volume of alcohol consumption, drinking patterns and related burden of
      mortality in young people in established market economies of Europe.
AB  - OBJECTIVE: To determine the burden of mortality in young people (age 15-29) in
      established market economies in Europe in 1999, which is attributable to alcohol
      consumption. Two dimensions of alcohol consumption were considered: average
      volume of consumption, and patterns of drinking. METHODS: Mortality data were
      obtained from the WHO EIP data bank, average volume data from the WHO global
      databank on alcohol, pattern of drinking data from a questionnaire sent out to
      experts, from the published literature and from the WHO global databank. Methods
      are explained and discussed in detail in two other contributions to this volume.
      RESULTS: More than 8,000 deaths of people aged 15-29 in Europe in 1999 were
      attributable to alcohol. Young males show a higher proportion of alcohol
      attributable deaths (12.8%) than females (8.3%). Both average volume and patterns
      of drinking contribute to alcohol-related death. CONCLUSIONS: Alcohol-related
      deaths constitute a considerable burden in young people in Europe.

PMID- 11509846
TI  - Persistent detection of alfa-fetoprotein in the vagina without overt preterm
      premature rupture of the membranes. Clinical and chemical characterizations.
AB  - OBJECTIVES: The objectives of this study were to clinically characterize and seek
      risk factors for the patients with persistently detected alfa-fetoprotein (AFP)
      in the vagina without showing overt preterm premature rupture of the membranes
      (PROM). STUDY DESIGN: The cohort study was undertaken using vaginal-cervical
      specimens collected consecutively between 21 and 40 weeks of gestation from 25
      consenting women. Demographic, obstetric, neonatal, and laboratory data from
      patients with persistent positive results of AFP kit tests without showing overt
      leakage of amniotic fluid were compared to those from controls. Cervical levels
      of interleukin-1 alpha, interleukin-1 beta, interleukin-6, interleukin-8, and
      granulocyte elastase were measured by immunoassay, and the uterine cervix was
      assessed by transvaginal ultrasonography. Statistical analysis involved Fisher's
      exact test and Mann-Whitney U test. RESULTS: The incidence of overt preterm PROM
      was significantly higher in the patients with persistently detected AFP in
      preterm (3 in 4 cases) than in controls (3 in 21 controls). At sampling before
      determination of persistently detected AFP, patients with persistently detected
      AFP had significantly higher cervical levels of interleukin-6 and significantly
      shorter cervical length than controls. CONCLUSIONS: Patients with persistently
      detected AFP in the vagina without showing overt preterm PROM have the risk of
      overt preterm PROM. Increased levels of interleukin-6 in cervical specimens and
      short cervical length may be risk factors for the occurrence of persistent
      detection of AFP in the preterm.

PMID- 11509847
TI  - Duplication dup(1)(q32q44) detected by comparative genomic hybridization (CGH):
      further delineation of trisomies 1q.
AB  - Partial trisomy 1q is rare and mostly the result of an abnormal segregation of
      parental translocation chromosomes and their homologues. Only 31 cases have been
      described with pure partial trisomy 1q. In the fetus presented, chromosome
      analysis after amniocentesis had shown an unbalanced male karyotype with an
      aberrant chromosome 1. A de novo terminal duplication of the long arm was
      suspected but could not be verified by FISH in 1994. Five years after fetal
      death, retrospective identification of the additional material in 1q could
      finally be achieved by comparative genomic hybridization (CGH) using DNA
      extracted from formalin-fixed and paraffin-embedded fetal tissues. A direct
      duplication dir dup (1)(pter-->q44::q32.1-->qter) was found. Only 6 other
      individuals with duplication of this segment have been described so far.
      Comparative delineation of a dup1q phenotype with regard to size and origin of
      the dup (1q) segment evidenced that large duplications as well as proximal and
      interstitial duplications coincide with more severe visceral malformations,
      severe mental retar- dation and a short life span. Terminal duplications (1q32-
      >qter) concur with less severe malformations and longer periods of survival, but
      marked mental retardation. With small terminal duplications (1q42-->qter)
      dysmorphisms are usually mild and intellectual performance is mostly in the
      normal range.

PMID- 11509848
TI  - Pulmonary atresia with hypoplastic right ventricle. A clinical embryological
      study.
AB  - An unusual case of pulmonary atresia with an aberrant karyotype of
      46,XX,t(6;8)(p21.2;q11.2) is reported. Fetal ultrasonic examination at the 20th
      week of gestation revealed a hypoplastic right ventricle and an intact
      interventricular septum. Authors summarize their postnatal findings in fetal
      heart and the large adjacent vessels with special reference to the pathogenesis
      of this rare congenital heart defect. The observation delineates right
      ventricular outflow tract obstruction associated with an abnormal pulmonary blood
      supply. The anatomy of the systemic pulmonary collaterals was studied and
      correlated with multifocal disorders in the system of the pharyngeal arch
      arteries in the early embryonic development.

PMID- 11509849
TI  - Mild ventriculomegaly, mild cerebellar hypoplasia and dysplastic choroid plexus
      as early prenatal signs of CHARGE association.
AB  - CHARGE association has been diagnosed postnatally in increasing numbers since the
      first description in 1979. The acronym CHARGE includes the abnormalities ocular
      Colobomas (iris, retina or nervus opticus), Heart disease, Atresia of choanae,
      Retarded growth and development and/or central nervous system anomalies, Genital
      hypoplasia, Ear anomalies and deafness. So far, no prenatal diagnosis of the
      CHARGE association has been described; only one case report presents prenatal
      symptoms detected at 31 gestational weeks. In our case, prenatally detected mild
      cerebral ventriculomegaly and dysplasia of choroid plexus were abnormalities
      visible as early as 15+6 weeks as well as mild cerebellar hypoplasia at 21+1
      weeks. At 28+6 weeks, in addition polyhydramnios could be found. The combination
      of the 'benign' central-nervous findings raised suspicion of a severe congenital
      malformation at 21+1 weeks which was confirmed postnatally in the form of
      diagnosis of CHARGE association.

PMID- 11509850
TI  - First-trimester diagnosis of sirenomelia. A case report.
AB  - We report a case of sirenomelia diagnosed at 13 gestational weeks. This rare
      malformation sequence is characterized by fusion and rotation of the lower limbs
      to various degrees and anorectal atresia, usually associated with absence of
      bladder and agenesis or dysgenesis of the kidneys. Diagnosis is commonly made
      later in the second trimester of pregnancy with oligohydramnios as the alerting
      sign. Survival is extremely rare, and only possible in the absence of bilateral
      renal agenesis. In view of the dismal prognosis, early diagnosis allows for
      earlier and less traumatic therapeutic abortion.

PMID- 11509851
TI  - Biochemical differentiation of gestational compartments in the midgestational
      fetal rabbit.
AB  - OBJECTIVES: The fetal rabbit at midgestation is increasingly being used as a
      model in fetal diagnosis and therapy. In this study, we aimed to establish a
      reliable method for identification of the origin of sampled extra-embryonic
      fluids based on selected biochemical components. METHODS: In 6 pregnant does at
      22 days of gestation, 18 gestational sacs were sampled for amniotic, allantoic
      and exocoelomic fluid. These fluids, as well as matching maternal and fetal blood
      samples, were assayed for levels of sodium, potassium, chloride, bicarbonate,
      total protein, alkaline phosphatase, gamma-glutamyl transferase and progesterone.
      RESULTS: Levels of sodium and potassium were, respectively, lower and higher in
      the allantoic fluid when compared to other extra-embryonic spaces. Amniotic fluid
      had a significantly lower total protein content and higher level of alkaline
      phosphatase when compared to the exocoelomic fluid. Significant levels of
      progesterone could only be detected in maternal blood. CONCLUSIONS: In the
      midgestational rabbit, a combined assay of potassium, alkaline phosphatase and
      progesterone can determine the gestational cavity of origin of the sampled fluid.
      The obtained gradients for these markers suggest compartment-specific production
      and/or inter-cavity transfer mechanisms.

PMID- 11509852
TI  - Management of anti-Rhesus-D antibodies in pregnancy: a review from 1994 to 1998.
AB  - OBJECTIVE: To review our management of anti-Rhesus-D antibodies in pregnancy over
      a 5-year period in order to assess possible changes in the management or
      prognosis which may have developed with time. METHOD: Retrospective analysis of
      prospectively collected data from 31 pregnancies with maternal anti-D levels >4
      IU/ml and in which the fetus was Rhesus positive. RESULTS: There were a total of
      30 amniocenteses, 8 cordocenteses, and 54 fetal blood transfusions performed.
      When undertaken as the first procedure, the mean gestational age at amniocentesis
      was 30 weeks as compared with 25 weeks for fetal blood sampling/transfusion (p <
      0.05). The median anti-D level at the first procedure was 24 IU/ml for
      amniocentesis and 64 IU/ml for fetal blood sampling. Of the 54 blood
      transfusions, 43 were intravascular, 4 were intraperitoneal, and 7 transfusions
      were both intravascular and intraperitoneal. CONCLUSIONS: Intravascular as
      opposed to intraperitoneal transfusions were found to be the main method of
      transfusion in the later years in this study, a finding which was expected with
      improved sonographic equipment. Apart from this, management and prognosis of anti
      D red cell isoimmunisation in pregnancy have remained relatively stable since the
      1980s. Amniocentesis was useful in the management of such pregnancies, especially
      as an initial procedure in the cases with a lower initial anti-D level. In this
      series 90% of the fetuses requiring blood transfusion, but were without hydrops,
      survived, whereas this was about 70%, if they had become hydropic (this latter
      figure was reduced by 2 hydropic deaths before 20 weeks' gestation in the same
      very severely affected woman).

PMID- 11509853
TI  - High-efficiency retroviral transduction of fetal liver CD38-CD34++ cells:
      implications for in utero and ex utero gene therapy.
AB  - OBJECTIVES: Defining methods for the efficient transduction of fetal stem cells
      could lead to novel fetal therapies for blood cell disorders and other birth
      defects. In this study, we analyzed the effects of various parameters on the
      retroviral transduction of primitive hematopoietic progenitors/stem cells
      isolated from fetal liver. METHODS: Candidate stem cells were isolated by
      fluorescence-activated cell sorting from midtrimester human livers based on the
      phenotype CD38-CD34++lineage- (lineage = glycophorin A, CD3, CD14, CD19, CD20 and
      CD56). A murine retroviral vector with a truncated human low-affinity nerve
      growth factor receptor (Delta NGFR) gene was used to transduce the candidate stem
      cells. Marker gene expression was monitored by flow cytometry using an anti-NGFR
      mAb. Candidate stem cells were transduced immediately after isolation or after up
      to 4 days of culture in serum-deprived medium containing the growth factors kit
      ligand and granulocyte-macrophage colony-stimulating factor. The effects on
      transduction efficiency of the addition of 4 microg/ml protamine sulfate and/or
      centrifugation to concentrate the candidate stem cells and virus were tested.
      After transduction, the cells were expanded for 10-21 days before determining the
      frequency of NGFR+ cells among the different hematopoietic progeny. RESULTS:
      Efficient transduction of candidate stem cells, at an average rate of 46%, was
      achieved after 3 days of culture with a single exposure to virus. Longer than 3
      days of culture or repeated exposure to viral supernatant did not significantly
      improve the rate of transduction. The use of centrifugation at 1,200 g for 1 h
      and the addition of protamine sulfate during the transduction procedure were
      critical to achieving a high rate of transduction. Marker gene expression was
      observed on the progeny of the transduced cells in conjunction with CD34
      (progenitors), glycophorin A (erythrocytes), CD14 (monocytes), CD15
      (granulocytes) and CD41 (megakaryocytes). CONCLUSIONS: This study demonstrates
      that the efficient transduction of fetal candidate stem cells can be achieved
      under defined culture conditions using a retroviral vector. These results
      encourage further examination of in utero and ex utero gene therapy as a means of
      treating birth defects.

PMID- 11509854
TI  - First-trimester diagnosis of Robinow syndrome.
AB  - We present 2 cases with Robinow syndrome in a nonconsanguineous Turkish couple.
      The first case, second living child of the family, has all of the cardinal
      features of this syndrome including short stature, mesomelic shortening of
      forearms, frontal bossing, hypertelorism, anteverted nares, triangular mouth,
      hypoplastic genitalia and vertebral and costal anomalies. The second case was
      diagnosed with first-trimester ultrasonographic findings such as shortening of
      extremities and increased nuchal translucency thickness at 12 + 4 weeks of
      gestation, and the family wished to terminate this pregnancy. After abortion, we
      obtained findings such as typical face features, shortening of forearms,
      ambiguous genitalia suggesting Robinow syndrome with autopsy examination.

PMID- 11509855
TI  - The Rationale for in utero repair of myelomeningocele.
AB  - OBJECTIVES: Despite advances in prenatal diagnosis, management of fetal
      myelomeningocele has been limited to abortion or supportive postnatal care. The
      rationale for fetal repair of myelomeningocele and initial clinical outcomes are
      discussed. METHODS: A complete review of the literature concerning fetal
      myelomeningocele and repair was performed. RESULTS: While myelomeningocele is a
      primary embryologic disorder, neurologic damage is also secondary to progressive
      in utero damage to the exposed spinal cord. Animal models with midgestational
      coverage of the spinal defect demonstrate near normal neurologic function at
      term. Early clinical results suggest that fetal closure can salvage neurologic
      function, reverse hindbrain herniation, and diminish the need for
      ventriculoperitoneal shunting. CONCLUSIONS: In utero repair of myelomeningocele
      may improve neurologic outcomes and reduce hindbrain herniation in selected
      patients.

PMID- 11509856
TI  - [Understanding the organism as a central problem medicine].
AB  - The history of scientific inquiries about the organism within medicine and
      biology is characterized by controversies about the adequate research methods and
      forms of explanation. These controversies continue well into our time. In
      different variations the more mechanistic approaches are opposed to the more
      vitalistic approaches, reductionistic approaches are opposed to the more holistic
      ones. Partly these different views are reflected in some of the differences
      between conventional and complementary medicine. This epistemologic inquiry
      discusses some of these approaches to show their potentials as well as their
      deficits. It is pointed at concepts that are searching for forms of explanation
      beyond mechanistic and vitalistic views. They are suitable to solve these long
      standing debates and to lead nearer to the specific properties of the organism.
      It is emphasized that it is important to further develop the concepts of an
      'organismic biology', and its relevance for medicine and medical research is
      demonstrated.

PMID- 11509857
TI  - [Complementary medicine and patient contentedness - a survey].
AB  - BACKGROUND: Increasing popularity and concomitant application of complementary
      and conventional methods by patients and doctors in Germany. INTENTION: To
      examine attitudes and patient contentedness. METHOD: Open, retrospective, postal
      survey in 1,582 female patients treated with complementary methods between 1991
      and 1996, using a structured trilateral questionnaire. RESULTS: Of 1,582 mailed
      questionnaires 808 (51%) were evaluable. About 50% of the patients in the survey
      felt that the results of their complementary treatment were 'very successful'
      (22%) or 'rather successful' (24%). 80% of the patients were 'very' oder 'rather
      satisfied' with the complementary treatment. This positive assessment was also
      found in patients without treatment success. 50% indicated a significant change
      in health behavior, more than two thirds indicated a change in life-style
      attitude. More than 90% of the patients would be ready to pay for part of their
      treatment. Half of the surveyed women used natural remedies without knowledge of
      their family doctor. Because of a low response rate of 50%, there is the
      possibility of selection bias which makes a cautious interpretation of these
      results necessary. CONCLUSION: Because of the approaches and methods applied,
      complementary medicine is particularly suited to induce patient treatment
      satisfaction. Further studies are necessary to verify positive long-term health
      effects of complementary interventions and treatment.

PMID- 11509858
TI  - [Effects of speech therapy with poetry on heart rate variability and well-being].
AB  - BACKGROUND: Anthroposophical Therapeutic Speech uses poems and exercises which
      typically induce rhythmical breathing. Speaking influences respiration and thus
      directly heart rate variability (HRV), in particular via respiratory sinus
      arrhythmia which, together with the slower rhythms of HRV, may be regarded as an
      indicator of sympathovagal balance. In chronomedicine numerous frequency ratios
      between physiological rhythms, especially in trophotropic phases, have been
      established. Integer ratios occur frequently and seem to be associated with the
      optimization of physiological processes. In larger groups the average pulse
      respiration quotient is about 4:1. QUESTION: Can systematic effects on HRV, and
      thus on autonomic balance, be established through special speech therapy?
      SUBJECTS AND METHODS: In two trained therapists and 7 untrained subjects the
      influence of different speech exercises and texts on HRV was investigated. With
      untrained subjects a total of 105 one-hour sessions, divided into speech and
      control exercises, was performed. The overall well-being and quality of well
      being were assessed with questionnaires. Control evaluations were made in the
      same setting. RESULTS: As a simultaneous effect, during speech exercises and
      texts typical intra- and inter-individually reproducible patterns in heart rate
      variability were observed. Reciting poems with a hexameter metric generates 2
      oscillations with a 2:1 frequency ratio in the HRV spectrum. As immediate effects
      there were a significant drop in heart rate after speech sessions as well as a
      strengthening of vagus-related HRV parameters, especially after hexameter
      exercises. In comparison to control sessions the subjects felt significantly
      better, too. The different metric and poetic character of the texts was reflected
      clearly in the results.

PMID- 11509859
TI  - [Homeopathy between vital force and self-organization].
AB  - The idea of the vital force served European 18th-century scientists as
      theoretical background and as an integration model for many popular theories. The
      vital force was used to explain why physiological processes occur in a practical,
      useful and functional way and to answer the questions about the nature of biotic
      organization. At the end of 18th century, Samuel Hahnemann, the founder of
      homeopathy, used the theory of the vital force as a theoretical basis to explain
      the effects of homeopathic treatment and to justify his medical system. Vitalists
      represented a holistic tradition, they were not willing to accept purely
      mechanical interpretations of biological phenomena. The discussion between
      holistic and mechanistic scientists resulted in the development of modern self
      organization theories, such as system, network, and chaos theory.The article
      gives an overview about the historical development from vital force to modern
      self-organization theories and discusses the relevance of the modern theories for
      homeopathic research.

PMID- 11509860
TI  - The serum concentration of tumor necrosis factor alpha is not an index of growth
      hormone- or obesity-induced insulin resistance.
AB  - BACKGROUND: The tumor necrosis factor alpha (TNF-alpha) might play a central role
      in insulin resistance, a frequent correlate of obesity likely contributing to
      some obesity-associated complications. Adult growth hormone (GH) deficiency
      syndrome (GHDA) shares with obesity excessive fat mass, hyperlipidemia, increased
      cardiovascular risk, and insulin resistance. On the other hand, GH has been shown
      to induce transient deterioration of glucose metabolism and insulin resistance
      when administered in normal humans and in GHDA patients. No information is
      presently available on the relationship between serum TNF-alpha levels and
      insulin sensitivity in GHDA. METHODS: We compared the serum TNF-alpha levels
      found in 10 GHDA patients before and after a 6-month recombinant human GH therapy
      (Genotropin), in an insulin resistance prone population of 16 obese (OB) patients
      and in 38 normal-weight healthy blood donors (controls). The insulin sensitivity
      was assessed by a euglycemic-hyperinsulinemic glucose clamp in all the GHDA
      patients and in 10 OB and in 6 control subjects. RESULTS: The serum TNF-alpha
      levels were not significantly different in OB patients (42.2 +/- 12.81 pg/ml), in
      GHDA patients at baseline (71.3 +/- 23.97 pg/ml), and in controls (55.3 +/- 14.28
      pg/ml). A slight decrease of TNF-alpha values was noted in GHDA patients after 6
      months of recombinant human GH treatment (44.5 +/- 20.19 pg/ml; NS vs. baseline).
      The insulin sensitivity (M) was significantly reduced in OB patients (2.4 +/-
      0.30 mg/kg/min) as compared with control subjects (7.5 +/- 0.39 mg/kg/min) and in
      GHDA patients both at baseline (6.6 +/- 0.6 mg/kg/min) and after recombinant
      human GH therapy (5.6 +/- 0.7 mg/kg/min). The insulin sensitivity in the GHDA
      patients, similar to that of controls at baseline, worsened after recombinant
      human GH treatment (p < 0.05 vs. baseline; p = 0.05 vs. controls). Linear
      regression analysis showed no correlation between TNF-alpha and M values (see
      text) in all patient groups. CONCLUSIONS: These data indicate that circulating
      concentrations of TNF-alpha do not reflect the degree of insulin resistance in
      obesity and GHDA. They, however, do not exclude that TNF-alpha may induce insulin
      resistance at tissue level.

PMID- 11509861
TI  - Insulin resistance in nonobese patients with polycystic ovary syndrome.
AB  - OBJECTIVES: Most patients with polycystic ovary syndrome (PCOS) are obese and
      known to have insulin resistance. Obesity per se is a cause of insulin
      resistance. This study was performed to determine whether insulin resistance
      occurs in patients with PCOS in the absence of obesity and acanthosis nigricans.
      METHOD: For this purpose, an euglycemic hyperinsulinemic clamp study was
      performed in 12 nonobese patients with PCOS and in 10 healthy control subjects
      matched for age and weight. RESULTS: The mean serum testosterone and luteinizing
      hormone (LH) levels were significantly elevated (4.09 +/- 1.32 vs. 1.18 +/- 0.53
      pg/ml, p < 0.001, and 11.63 +/- 5.37 vs. 4.98 +/- 2.73 mIU/ml, p < 0.001,
      respectively), and the serum sex hormone binding globulin level was significantly
      reduced (40.96 +/- 14.94 vs. 73.98 +/- 30.40 nmol/l, p < 0.001) in patients with
      PCOS as compared with the values in control subjects. The mean serum insulin
      level was also elevated in patients with PCOS as compared with control subjects
      (32.33 +/- 4.98 vs. 19.56 +/- 2.21 microU/ml, p < 0.05). The insulin sensitivity
      was lower in patients with PCOS as compared with the control subjects (200 +/-
      27.8 vs. 427.8 +/- 88.9 micromol x kg(-1) x min(-1), p < 0.001). In patients with
      PCOS, the serum levels of free testosterone (r = -0.89, p < 0.001) and LH were
      inversely correlated with the insulin sensitivity (r = -0.63, p < 0.05). Serum
      follicle-stimulating hormone, prolactin, and dehydroepiandrosterone sulfate
      levels were similar in both groups. CONCLUSIONS: These results indicate that a
      significant degree of insulin resistance exists in nonobese patients with PCOS
      and that this insulin resistance is significantly related to serum LH and free
      testosterone levels. Thus, measures to decrease insulin resistance may have to be
      considered earlier to decrease the potential risks of developing diabetes
      mellitus and coronary artery disease at later ages of life in these patients.

PMID- 11509862
TI  - Radiological signs of Leri-Weill dyschondrosteosis in Turner syndrome.
AB  - BACKGROUND/AIMS: Leri-Weill dyschondrosteosis (LWD), a mesomelic short stature
      syndrome with Madelung deformity, was recently reported to be caused by SHOX
      (short stature homeobox-containing gene) haploinsufficiency. The loss of SHOX on
      Xp22.32, also called PHOG (pseudoautosomal homeobox-containing osteogenic gene),
      through structural aberrations of the X chromosome was also implicated in the
      short stature phenotype and some additional stigmata of Turner syndrome. The aim
      of this study was to systematically examine left-hand radiographs from Turner
      girls for the presence of signs of LWD. METHODS: We retrospectively studied 168
      left-hand radiographs from 54 patients with Turner syndrome (bone age >10.5
      years) who were treated with rhGH and seen during the last 10 years in our
      clinic. For comparison, we analyzed 7 radiographs from 5 patients with LWD and 52
      radiographs from 20 patients with GH deficiency. The shape of the distal radial
      epiphysis (triangularisation index = TI) and the carpal angle were quantitatively
      measured. In addition, we screened for the presence of a premature cleft fusion
      or an ulnar deviation of the articular surface of the distal radial epiphysis and
      for fourth metacarpal shortening. One of 54 Turner girls (2%) was affected with
      LWD and presented with Madelung deformity. RESULTS: No milder forms of Madelung
      deformity were detected. However, there was a significant trend to a triangular
      shape of the distal radial epiphysis in Turner syndrome: the median TI was 2.7 in
      normal controls (range 1.8-3.7), 3.1 in Turner girls (range 2.0-6.3) (p < 0.001
      against controls), and 6.0 in patients with LWD (range 3.5-11.0) (p < 0.001
      against controls). CONCLUSIONS: The triangularisation index did not correlate
      with the carpal angle (median 122.5

PMID- 11509863
TI  - Frasier syndrome with childhood-onset renal failure.
AB  - BACKGROUND: The Wilms' tumour 1 (WT1) gene encodes a protein which is believed to
      exert transcriptional and tumour-suppressor activities. Mutations of this gene
      have occasionally been associated with Wilms' tumour (<15% of cases) and, more
      consistently, with three syndromes characterized by urogenital abnormalities
      (WAGR, Denys-Drash and Frasier syndrome). SUBJECT/METHOD: A 25-year-old
      phenotypic female with a 46,XY karyotype presented with amenorrhoea. An
      ultrasound scan showed streak gonads and a rudimentary uterus. The patient had a
      history of post-streptococcal glomerulonephrosis, when aged 4 years, which had
      rapidly progressed to kidney failure, requiring transplantation at age 8. RESULT:
      Frasier syndrome was suspected and confirmed by genetic analysis. In fact, direct
      sequencing of the PCR product of the intron 9 donor splice site revealed a
      substitution of guanine for adenine in position +5. CONCLUSION: Besides being one
      of the few Frasier syndrome cases to be genetically characterized, this case is
      interesting because of the unusually early-onset renal failure.

PMID- 11509864
TI  - Decreased levels of ionized calcium one year after hemithyroidectomy: importance
      of reduced thyroid hormones.
AB  - BACKGROUND: Previously we have found reduced levels of total serum calcium and
      1,25(OH)2D3 despite an unaltered stimulated parathyroid hormone (PTH) secretion 1
      year after hemithyroidectomy. The present study was undertaken to elucidate the
      possible relationship between calcium homeostasis, thyroid hormones and bone
      resorption in a group of 45 consecutive patients subjected to hemithyroidectomy
      because of a solitary nodule. All patients had free T4 and T3 levels within
      normal range preoperatively. METHODS: Thyroid hormones, bone mineral and
      biochemical variables known to reflect calcium homeostasis were studied. Patients
      were divided into three separate groups depending on their pre- and postoperative
      thyroid hormone status. RESULTS: One year postoperatively, serum levels of free
      T4 were decreased and that of thyrotropin (TSH) increased in the entire group of
      patients. The concentration of ionized calcium was reduced from 1.25 +/- 0.05 to
      1.22 +/- 0.04 (p < 0.001) despite an unaltered PTH value (2.8 +/- 1.0 vs. 3.1 +/-
      1.5, p = 0.50). A significant reduction in C-terminal telopeptide type 1 collagen
      (1CTP) indicated decreased bone resorption 1 year after surgery (p < 0.05).
      Subgroup analysis showed that a reduction in ionized calcium was seen only among
      patients with a postoperative decrease in free T4. Patients with subclinical
      hyperthyroidism preoperatively presented the lowest postoperative levels of
      ionized calcium, significantly reduced levels of 1CTP and increased levels of
      phosphate and creatinine. Multiple linear regression analysis showed that age (p
      < 0.05) and postoperatively changed serum levels of TSH (p < 0.05), creatinine (p
      < 0.05), phosphate (p < 0.001) and FT4 (p < 0.01) were independently associated
      with altered levels of ionized calcium. CONCLUSION: We conclude that the
      reduction in ionized calcium 1 year after hemithyroidectomy was not due to PTH
      deficiency. Instead our results suggest that the reduced effects of thyroid
      hormones on bone and kidney function is essential.

PMID- 11509865
TI  - Final height in children with idiopathic growth hormone deficiency treated with
      recombinant human growth hormone: the Belgian experience.
AB  - BACKGROUND: The growth response to recombinant hGH (rhGH) treatment and final
      height of 61 Belgian children (32 boys) with idiopathic growth hormone deficiency
      (GHD) were studied. PATIENTS/METHODS: Two patient groups were compared: Group 1
      with spontaneous puberty (n = 49), Group 2 with induced puberty (n = 12). The
      patients were treated with daily subcutaneous injections of rhGH in a dose of 0.5
      0.7 IU/kg/week (0.17-0.23 mg/kg/week) from the mean +/- SD age of 11.9 +/- 3.1
      years during 5.1 +/- 2.1 years. RESULTS: rhGH treatment induced a doubling of the
      height velocity during the first year and resulted in a normalisation of height
      in 53 (87%) patients. Final height was -0.7 +/- 1.1 SDS, being 170.4 +/- 7.2 cm
      in boys and 158.0 +/- 6.4 cm in girls. Corrected for mid-parental height, final
      height was 0.0 +/- 1.1 SDS. Ninety-two percent of the patients attained an adult
      height within the genetically determined target height range. Although height
      gain during puberty was smaller in the patients with induced puberty (boys: 17.1
      +/- 7.0 cm vs. 27.5 +/- 6.6 cm (p < 0.005); girls: 9.6 +/- 7.4 cm vs. 22.2 +/-
      6.1 cm (p < 0.005)), no differences in final height after adjustment for mid
      parental height were found between patients with spontaneous or induced puberty.
      CONCLUSIONS: We conclude that patients with idiopathic GHD treated with rhGH
      administered as daily subcutaneous injections in a dose of 0.5-0.7 IU/kg/week
      reach their genetic growth potential, resulting in a normalisation of height in
      the majority of them, irrespective of spontaneous or induced puberty.

PMID- 11509866
TI  - No influence of prednisolone on IGFBP-3 proteolysis in healthy young men.
AB  - AIMS: The impact of growth hormone (GH) and prednisolone on the GH/insulin-like
      growth factor (IGF) axis with special emphasis on IGF binding protein-3 (IGFBP-3)
      proteolysis was studied in 8 healthy adults in a double-blind cross-over study
      with four periods: (1) placebo; (2) s.c. GH 0.1 IU/kg/day; (3) oral prednisolone
      50 mg/day, and (4) co-administration of GH and prednisolone. METHODS: Each
      treatment period lasted for 4 days followed by a washout period of 10 days. We
      measured IGF-I, IGF-II, IGFBP-1, IGFBP-2, IGFBP-3 by immunoassays, IGFBP-3 by
      Western ligand blotting (WLB) and finally in vitro IGFBP-3 proteolysis by a
      (125)I-IGFBP-3 degradation assay. RESULTS: IGF-I levels increased by 99% during
      GH administration and 67% during co-administration of GH and prednisolone (p <
      0.0005), whereas no significant change was seen during prednisolone alone. IGFBP
      1 levels decreased 55% during the prednisolone period (p < 0.002), but the
      between period changes were not significant (p < 0.1). IGFBP-2 decreased 33%
      during co-administration of GH and prednisolone (p < 0.002). IGFBP-3 increased
      12% during GH and 7% during co-administration of GH and prednisolone (p < 0.003
      and p < 0.03 compared to placebo, respectively), whereas prednisolone alone
      induced no significant changes. IGFBP-3 measured by WLB did not change
      significantly, neither did IGFBP-3 proteolysis. CONCLUSIONS: Prednisolone
      administration induces only minimal changes in circulating components of the IGF
      axis and is not accompanied by alterations in IGFBP-3 proteolysis. This indicates
      that the metabolic effects of glucocorticoids do not depend on serum IGF-I.

PMID- 11509867
TI  - Discordant growth pattern and ovarian function in monozygotic twins with
      45,X/46,XX mosaicism.
AB  - BACKGROUND: We report on phenotypically discordant female monozygotic twins with
      45X/46,XX mosaicism in both lymphocytes and fibroblasts. RESULTS: At 11.5 years,
      twin A was prepubertal, her height was 126.8 cm (-3.15 SD), bone age (BA) 9.7
      years (TW2), FSH 47 IU/l and IGF-I 280 ng/ml (-0.89 SD), but twin B was pubertal
      (P2, B3), her height was 143.4 cm (-0.92 SD), BA 13.6 years (TW2), FSH 3.4 IU/l
      and IGF-I 380 ng/ml (-0.21 SD). One year later, twin A had grown 11.1 cm due to
      growth hormone therapy and had IGF-I 1,400 ng/ml (+5.91 SD), whereas the growth
      velocity of twin B (no therapy) was 5.9 cm, IGF-I 540 ng/ml (+0.57 SD) and she
      started regular menstruation at 12.1 years. CONCLUSION: To our knowledge, this is
      the first report on monozygotic twins with Turner mosaicism in both lymphocytes
      and fibroblasts who developed a discordant phenotype probably due to an unequal
      distribution of the two cell lines in distinct tissues.

PMID- 11509868
TI  - Recent advances in the development of peptide vaccines for hepatitis B.
AB  - The control of hepatitis B by vaccination is arguably one of medicine's greatest
      achievements in terms of protecting infants and adults at high risk of infection.
      Paradoxically, however, the existence of a large reservoir of chronically
      infected individuals will not diminish the risk of infection by those coming into
      close contact with such persons until universal infant immunisation is practised
      globally and vaccines are in place to ensure maximum efficacy in those with
      impaired immune responses, immunity is achieved with fewer doses, and
      immunisation as an adjunct to the antiviral treatment of chronic carriers is
      adopted. These imperatives have continued to stimulate research into vaccines
      based on chemically synthesised short peptides, and those systems best suited for
      their delivery. This review discusses the potential of synthetic peptide
      formulations as efficient inducers of both humoral and cellular immune responses
      against hepatitis B, and reviews recent advances in peptide delivery. Synthetic
      peptide and delivery systems technologies will, amongst others, be of paramount
      importance in the global fight for the eradication of hepatitis B in the 21st
      century.

PMID- 11509869
TI  - DNA vaccines for prophylactic or therapeutic immunization against hepatitis B.
AB  - DNA-based or genetic vaccination is an efficient new technique to stimulate
      specific immune responses after in vivo delivery of bacterial plasmids encoding
      antigens. In mice and in various other animal models for hepadnavirus infection,
      DNA vaccines specific for hepatitis B virus (HBV) antigens induce a strong
      humoral and cell-mediated immunity that confers protection in some models.
      Although there are effective prophylactic vaccines already available for HBV,
      there is currently no effective treatment for chronic HBV infection. Patients
      with HBV-associated liver disease are at increased risk of developing
      hepatocellular carcinoma and would greatly benefit from the availability of a
      therapeutic vaccine against HBV. By inducing immune responses closely related to
      those involved in clearing virus from the host, DNA vaccines may represent an
      alternative therapeutic approach for chronic HBV infection.

PMID- 11509870
TI  - A novel, recombinant triple antigen hepatitis B vaccine (Hepacare).
AB  - Infection with hepatitis B virus (HBV) continues to be a major problem in the
      human population. There remains a specific requirement for HBV vaccines capable
      of circumventing the non-responder/inadequate responder status of some vaccinees.
      Hepacare has been primarily developed to (1) improve anti-SHBs antibody titres in
      low responders, to conventional SHBsAg vaccinees, (2) overcome difficulties of
      non-compliance seen with existing SHBsAg vaccine regimens. Hepacare is a novel
      recombinant particle produced in eukaryotic cells, consisting of pre-S1, pre-S2
      and S proteins of HBV and is adjuvanted with alhydrogel. It has been demonstrated
      to be highly immunogenic for both B and T cells in mice, chimpanzees and humans
      and induces higher anti-S 'a' determinant antibody titres than SHBsAg vaccines in
      mice and humans. Hepacare has proven to be at least as efficacious as current
      SHBsAg vaccines in chimpanzees. Clinical trials in both Europe and the USA have
      clearly demonstrated its superior ability to induce anti-SHBs antibody
      seroconversion in low-responder groups, compared with SHBsAg vaccines.

PMID- 11509871
TI  - HBV core particles as a carrier for B cell/T cell epitopes.
AB  - In the middle 80s, recombinant hepatitis B virus cores (HBc) gave onset to
      icosahedral virus-like particles (VLPs) as a basic class of non-infectious
      carriers of foreign immunological epitopes. The recombinant HBc particles were
      used to display immunodominant epitopes of hepatitis B, C, and E virus, human
      rhinovirus, papillomavirus, hantavirus, and influenza virus, human and simian
      immunodeficiency virus, bovine and feline leukemia virus, foot-and-mouth disease
      virus, murine cytomegalovirus and poliovirus, and other virus proteins, as well
      as of some bacterial and protozoan protein epitopes. Practical applicability of
      the HBc particles as carriers was enabled by their ability to high level
      synthesis and correct self-assembly in heterologous expression systems. The
      interest in the HBc VLPs was reinforced by the resolution of their fine structure
      by electron cryomicroscopy and X-ray crystallography, which revealed an unusual
      alpha-helical organization of dimeric units of HBc shells, alternative packing
      into icosahedrons with T = 3 and T = 4 symmetry, and the existence of long
      protruding spikes. The tips of the latter seem to be the optimal targets for the
      display of foreign sequences up to 238 amino acid residues in length. Combination
      of numerous experimental data on epitope display with the precise structural
      information enables a knowledge-based design of diagnostic, and vaccine and gene
      therapy tools on the basis of the HBc particles.

PMID- 11509872
TI  - Modulation of gene-gun-mediated Th2 immunity to hepatitis B surface antigen by
      bacterial CpG motifs or IL-12.
AB  - Using different DNA vaccination techniques, we studied the IgG1/IgG2a antibody
      and MHC-I-restricted cytotoxic T lymphocyte (CTL) responses to the hepatitis B
      surface antigen (HBsAg) in mice. A single intramuscular injection of 100 microg
      HBsAg-encoding pCI/S plasmid DNA efficiently primed IgG2a antibody (IgG1/IgG2a
      ratio <0.3) and CTL responses to HBsAg (Th1 immunity). In contrast, a single
      intradermal injection of 1 microg of particle-coated pCI/S DNA with the gene-gun
      primed IgG1 antibody responses to HBsAg (IgG1/IgG2a ratio >80) but there was no
      CTL response (Th2 immunity). Injection of immune-stimulating CpG-containing
      oligodeoxy-nucleotides (ODN) into the skin area used for gene-gun-mediated pCI/S
      DNA delivery shifted the polarization of the response towards Th1 immunity. A
      similar shift from Th2 to Th1 immunity was observed when the skin area used for
      gene-gun-mediated DNA transfer was conditioned by injection of recombinant IL-12.
      DNA vaccination can thus prime polarized immunity to HBsAg. The polarization of
      immunity is determined by the technique of plasmid DNA delivery as well as by
      conditions of the tissue into which DNA is inoculated. Th1 immunity to HBsAg
      (primed by injection of naked pCI/S DNA) dominated Th2 immunity (primed by gene
      gun-mediated pCI/S DNA). In contrast, an established HBsAg-specific Th2 immunity
      was readily shifted towards Th1 immunity (including specific CTL priming) by an
      intramuscular boost injection of pCI/S DNA. These data contribute to the rational
      design of DNA vaccination strategies to efficiently prime anti-viral Th1 immune
      effector specificities using the gene gun.

PMID- 11509873
TI  - Evaluation of new approaches to prophylactic and therapeutic vaccinations against
      hepatitis B viruses in the woodchuck model.
AB  - The woodchuck model is most suitable for vaccine studies of prophylaxis and
      therapeutic treatment of hepatitis B virus infection. Recently, methodological
      advances allowed the examination of antigen-specific T cell responses in
      woodchucks during woodchuck hepatitis virus (WHV) infection and vaccinations.
      Similar to hepatitis B virus infection in humans, multispecific T-cell responses
      to WHV occur during acute self-limiting infection in woodchucks. Immunizations
      with WHV core antigen (WHcAg) or DNA vaccines expressing WHcAg demonstrated that
      priming of specific T-cell responses leads to the control of WHV infection. B
      cell responses but no T-cell responses to WHV surface antigens (WHsAg) were
      induced in chronically WHV-infected woodchucks by the therapeutic immunizations
      with WHsAg. Breaking T-cell tolerance appears to be critical for
      immunotherapeutic approaches to chronic hepatitis B.

PMID- 11509874
TI  - Studies of hepatitis C virus in chimpanzees and their importance for vaccine
      development.
AB  - Persistent infection with hepatitis C virus (HCV) is an important cause of
      chronic liver disease worldwide. Therefore, the development of vaccines to
      prevent HCV infection, or at least to prevent progression to chronicity, is a
      major goal. Potential HCV vaccine candidates include recombinant proteins,
      recombinant viruses, DNA constructs, synthetic peptides and virus-like particles.
      Various vaccine candidates have been shown to generate humoral and cellular
      immune responses in animals, primarily in mice. However, the efficacy of most
      vaccine candidates in protecting against HCV has not been tested because the
      chimpanzee, the only animal other than humans that is susceptible to HCV, is not
      readily available, requires special facilities, and is very expensive. The course
      of infection in chimpanzees is similar in its diversity to that in humans and
      detailed studies in this model are beginning to define the immune responses that
      can terminate HCV infection. Of relevance for vaccine evaluation was the
      titration in chimpanzees of different HCV variants to provide well-characterized
      challenge pools. In addition, monoclonal virus pools generated from chimpanzees
      infected with cloned viruses make it possible now to examine immunity to HCV
      without the confounding factor of antigenic diversity of the challenge virus
      (quasispecies). The vaccine trials performed in chimpanzees to date all have
      tested the efficacy of immunizations with various forms of the envelope proteins
      of HCV.

PMID- 11509875
TI  - DNA vaccines for hepatitis C virus.
AB  - Hepatitis C virus is an RNA encoded virus of the Flaviviridae family. In most
      cases, infections develop into a chronic carrier stage that can result in the
      onset of cirrhosis and hepatocellular carcinoma over a 20- to 30-year period.
      Because existing therapies are still of limited benefit and expensive, the
      development of a vaccine represents a priority to prevent further spreading of
      the infection. Immune correlates of protection remain poorly defined although
      increasing evidence suggests that both humoral and cellular immune responses are
      likely to contribute to protection and/or neutralization of the virus. Current
      DNA-based vaccines, while capable of generating the latter, appear limited in
      their capacity to induce a strong and long-lasting antibody response.

PMID- 11509876
TI  - Vaccination against hepatitis delta virus infection: studies in the woodchuck
      (Marmota monax) model.
AB  - Hepatitis delta virus (HDV) superinfection of hepatitis B virus carriers causes
      severe liver disease and results in a high rate of chronicity. So far, neither
      sufficient therapy nor vaccines to prevent HBV carriers from superinfection are
      available. A good model to test vaccine candidates is the woodchuck chronically
      infected with the woodchuck hepatitis virus (WHV); the woodchuck can be
      superinfected with HDV and shows a course of infection similar to that of
      patients. Different strategies have been investigated to establish a protective
      vaccine against HDV superinfection. Both proteins of HDV (HDAg p24 and p27),
      which differ only in the C-terminal amino acid sequence, have been used as
      vaccine candidates. Synthetic peptides derived from B cell epitopes of HDAg and
      HDAg p24 expressed in Escherichia coli, yeast, or baculovirus have been used to
      immunize woodchucks. The protein immunization induced a specific antibody
      response, however, no protection from HDV superinfection was achieved.
      Vaccinations with vaccinia virus expressing HDAg p24 or p27 and DNA immunization
      with vectors expressing p24 were also not able to induce a protective immune
      response, but seemed to modulate the course of HDV superinfection. Thus, new
      strategies to develop a vaccine to prevent HDV superinfection are needed.

PMID- 11509877
TI  - Perspectives of vaccination against hepatitis E.
AB  - Hepatitis E, an important cause of morbidity and mortality in humans, accounts
      for more than 50% of acute viral hepatitis in young adults in developing
      countries with a 20-30% mortality rate among infected pregnant women primarily
      those in their third trimester. The development of inactivated or live attenuated
      virus vaccine has been hampered because this virus does not replicate efficiently
      in cell culture. A vaccine has been developed by an alternative approach through
      recombinant technology. Preliminary results of the first administration in man
      conducted in the US at Walter Reed Army Institute of Research indicate the
      vaccine to be safe and immunogenic and have led to the decision to further
      evaluate the vaccine in an endemic setting.

PMID- 11509878
TI  - Therapeutic vaccines for human papillomaviruses.
AB  - Although papillomavirus infections are not very immunogenic there is evidence
      that the immune system controls the spread of virus and the development of
      diseases associated with such infections. Certain types of human papillomaviruses
      (HPV) are the major cause of premalignant and malignant diseases of the
      anogenital tract, most notably cancer of the uterine cervix, a major health care
      problem worldwide. Since the viral oncoproteins E6 and E7 are constitutively
      expressed within the tumor cells, they are considered as suitable targets for
      attack by T lymphocytes. Several approaches to specifically trigger a cell
      mediated immune response have been successful in experimental animals, leading to
      suppression of HPV-induced tumors. First clinical trials have been completed
      which raise hopes that a similar effect can also be achieved by therapeutic
      vaccination of humans.

PMID- 11509879
TI  - Development of new vaccines against dengue fever and Japanese encephalitis.
AB  - Mosquito-borne dengue (DEN) and Japanese encephalitis (JE) viruses are the
      leading causes of arthropod-transmitted viral disease in humans. A licensed
      tetravalent vaccine that provides effective, long-term immunity against all four
      serotypes of DEN virus is needed, but is currently unavailable. Improvements to
      currently available JE vaccines are also needed. Past and recent strategies for
      the development of new DEN and JE vaccines include inactivated and live
      attenuated viruses, engineered viruses and chimeric viruses derived from
      infectious cDNA clones of DEN or JE virus, recombinant poxviruses, recombinant
      baculoviruses, protein expression in Escherichia coli, and naked DNA vaccines.
      This report summarizes some of the recent developments in DEN and JE vaccinology,
      particularly vaccine strategies that involve live attenuated viruses, engineered
      viruses derived from infectious cDNA clones, and naked DNA vaccines.

PMID- 11509880
TI  - Dendritic cells and chronic hepatitis virus carriers.
AB  - Many individuals infected with hepatitis B virus (HBV) and hepatitis C virus
      (HCV) are unable to clear these viruses following an acute infection and become
      chronically infected. There are more than 400 million HBV and HCV carriers in the
      world and a considerable number of these patients would eventually develop more
      severe complications like liver cirrhosis and hepatocellular carcinoma. It is not
      clearly known how an individual develops a chronic hepatitis virus carrier state;
      however, a defective immune response of the host is thought to play a critical
      role in the underlying pathogenetic mechanism. On the other hand, dendritic cells
      (DCs), the most potent antigen-presenting cells, are widely distributed in both
      lymphoid and nonlymphoid tissues. Recognition of the microbes or microbial
      antigens by DCs is one of critical events for the initiation of an immune
      response. DCs also play a cardinal role during the progression and termination of
      an immune response. The aim of this overview is to provide information regarding
      the role of DCs in the pathogenesis of chronic hepatitis due to HBV and HCV in
      humans and in animal models of HBV and HCV carrier states. First, we summarize
      our current understanding of the pathogenesis of hepatitis virus carrier states
      and also of general properties of DCs. Next, we discuss the data on the
      phenotypes and functions of DCs in both human and murine HBV and HCV carriers. We
      also discuss vaccine therapy in murine HBV carriers because activation of DCs due
      to vaccination-initiated HBsAg-specific immune responses in HBV transgenic mice
      (HBV-Tg), which in turn resulted in complete clearance of hepatitis B surface
      antigen and hepatitis B e antigen and decreased levels of HBV DNA in some HBV-Tg.
      Finally, we discuss the extracted questions and future research directions.

PMID- 11509881
TI  - Effects of cyclosporin A on cell fusion in a monkey kidney cell line persistently
      infected with measles virus.
AB  - The authors studied the effects of immunosuppressive peptide cyclosporin A (CsA)
      on cell fusion efficiency in cells persistently infected with measles virus (448
      PI-Vero cells). Treatment of 448-PI-Vero cells with 5 microM CsA enhanced the
      infusion. In addition, the expression of measles virus antigen on cell surface
      was increased by treatment with CsA. The addition of phenothiazine, an anti
      calmodulin drug, enhanced the fusion of 448-PI-Vero cells in the presence of CsA,
      although treatment with phenothiazine alone did not affect polykaryocyte
      formation. The enhancement of fusion efficiency in 448-PI-Vero cells by CsA was
      suppressed by oligopeptide Z-D-Phe-Phe-Gly, a synthetic oligopeptide that
      inhibits fusion induced by measles virus. Since the cell content of major virus
      specific polypeptides, such as hemagglutinin, nucleoprotein or matrix protein is
      the same as in untreated controls, this fusion enhancement may be related to
      transport and accumulation of measles virus glycoproteins.

PMID- 11509882
TI  - Hepatitis C virus and GBV-C/hepatitis G virus in Argentine patients with
      porphyria cutanea tarda.
AB  - To investigate hepatitis C virus (HCV) and GBV-C/hepatitis G virus (HGV) genotype
      prevalence among HCV-infected porphyria cutanea tarda (PCT) patients, 19 HCV
      infected patients with associated PCT were studied. A control group of 53 age
      matched HCV-infected patients without associated PCT was selected. Eighteen of
      the 19 serologically positive HCV-PCT patients showed HCV RNA in serum. Genotype
      1b was the most prevalent among both HCV-PCT patients (72.2%; 13/18) and age
      matched HCV controls (50.9%; 27/53). Such different genotypic prevalence failed
      to reach statistical significance (chi(2) with Yates' correction, p = 0.19). The
      single HCV-PCT patient without detectable HCV RNA was also infected with
      genogroup 3 GBV-C/HGV. This GBV-C/HGV RNA prevalence (5.3%) among HCV-PCT
      patients is not statistically different from that observed among Argentine blood
      donors (5.5%; 11/200). To our knowledge, these results show for the first time
      the molecular epidemiology of both HCV and GBV-C/HGV associated to PCT in
      America.

PMID- 11509883
TI  - Roles of TT virus infection in various types of chronic hepatitis.
AB  - An unenveloped single-stranded virus, which might be a causative agent for
      posttransfusion non-A-G hepatitis, was recently found and named "TT virus" (TTV).
      There is still controversy over the role of TTV in chronic hepatitis. Therefore,
      we have examined the prevalence of TTV in various types of chronic hepatitis in
      Japan. TTV DNA was detected in 11 of 40 patients (27.5%) with non-B, non-C
      chronic hepatitis, 13 of 46 patients (28.3%) with type B chronic hepatitis, 21 of
      55 patients (38.2%) with type C chronic hepatitis, and 41 of 131 subjects (31.3%)
      with normal liver function tests. The positivity rate for TTV DNA tended to
      increase with age. The detection rate did not differ statistically between non-B,
      non-C chronic hepatitis and type B or type C chronic hepatitis, or normal
      subjects. The distribution of TTV genotypes was not significantly different among
      them. Clinical characteristics of the chronic illness were similar for patients
      with or without TTV in all hepatitis groups. The etiologic role of TTV in chronic
      hepatitis is not confirmed from the statistical and clinical standpoint.

PMID- 11509884
TI  - Murine cytomegalovirus infection induces cellular folylpolyglutamate synthetase
      activity in quiescent cells.
AB  - Cytomegalovirus (CMV) infection stimulates the expression of cellular enzymes
      involved in the biosynthesis of DNA precursors. Among them, dihydrofolate
      reductase (DHFR) and thymidylate synthase (TS) require folate as coenzymes. In
      growing cells, folates are readily converted to polyglutamated forms by the
      cellular enzyme folylpolyglutamate synthetase (FPGS). Polyglutamated folates are
      selectively retained within the cell and have an increased affinity for DHFR and
      TS. Here we report that murine CMV (MCMV) increases the levels of the FPGS mRNAs
      as well as the enzymatically active FPGS protein through a mechanism that
      requires viral gene expression. FPGS induction by MCMV would provide the
      necessary supply of polyglutamated folates to the cellular enzymes involved in
      the biosynthesis of deoxyribonucleotides, enabling viral DNA replication to take
      place in quiescent cells.

PMID- 11509885
TI  - Significance of serum matrix metalloproteinases and their inhibitors on the
      antifibrogenetic effect of interferon-alfa in chronic hepatitis C patients.
AB  - OBJECTIVE AND METHODS: The imbalance between matrix metalloproteinases (MMPs) and
      tissue inhibitors of matrix metalloproteinases (TIMPs) is considered to be an
      important determination of deposition and breakdown of the extracellular matrix.
      To investigate the antifibrogenetic effect of interferon-alpha (IFN-alpha)
      treatment on factors regulating hepatic fibrosis, serum MMP-1, MMP-2, TIMP-1 and
      TIMP-2 levels were measured by the one-step sandwich enzyme immunoassay in 27
      patients with chronic hepatitis C and compared with the histological status of
      the patients before and at the end of treatment. RESULTS: After 6 months of IFN
      alpha treatment, the histological status of liver fibrosis showed improvement in
      9 patients (IF group) and no change or a worsening in 18 patients (NIF group).
      Compared with pretreatment levels, in the IF group, IFN treatment caused a
      significant increase in the MMP-1/TIMP-1 ratio. In the NIF group, however, the
      MMP-1/TIMP-1 ratio tended towards a decrease; moreover, there was not only a
      significant increase in TIMP-2 levels but also a tendency towards an increase in
      TIMP-1 levels. CONCLUSION: These results suggested that an elevated MMP-1/TIMP-1
      ratio may ameliorate liver fibrosis by interferon in cases of chronic hepatitis
      C, whereas elevated levels of TIMP-1 and TIMP-2 might impede improvement.

PMID- 11509886
TI  - Replication-competent herpes simplex virus type 1 mutant expressing an
      autofluorescent glycoprotein H fusion protein.
AB  - The heterocomplex of glycoproteins H (gH) and L (gL) of herpes simplex virus type
      1 (HSV-1) is essential for viral infectivity and is involved in viral
      penetration, cell-to-cell spread, and syncytium formation. We constructed an HSV
      1 mutant expressing a gH-EGFP (enhanced green fluorescent protein) fusion protein
      under the control of the gH true late promoter. The EGFP coding sequence was
      cloned after the gH signal peptide into the HSV-1 genome. Superinfection of
      transfected, gH-nontranscomplementing cells with gH-negative HSV-1 resulted in a
      replication-competent recombinant virus. Cells infected with the recombinant
      virus exhibited strong and stable EGFP-specific fluorescence late in infection,
      and autofluorescence was detected in purified virions. The recombinant genotype
      of the mutant was confirmed by PCR. The 140-kD gH-EGFP fusion protein showed an N
      linked glycosylation pattern similar to gH-1, was recognized by the conformation
      dependent gH-specific monoclonal antibodies 52S and LP11 and formed a
      heterocomplex with gL which was transported to the cell surface and integrated
      into the viral envelope. Infectivity of the gH-EGFP mutant was neutralized by
      antibodies 52S and LP11. To our knowledge, this is the first replication
      competent HSV-1 mutant expressing an autofluorescent essential glycoprotein which
      will be a versatile tool for studies of penetration, late gene expression,
      transport and tissue spread.

PMID- 11509887
TI  - Nucleotide sequence of the precore/core gene and X gene of hepatitis B virus DNA
      in asymptomatic hepatitis B virus carriers who are negative for serum hepatitis B
      core antibody.
AB  - A hepatitis B virus (HBV) carrier who is positive for hepatitis B surface (HBs)
      antigen but negative for hepatitis B core (HBc) antibody despite persistent HBV
      infection, is designated as having hepatitis B virus 2 (HBV2). HBV2 is reported
      to be induced by mild-grade hepatitis. Patients with HBV2 have been reported in
      Taiwan and Senegal. In the present study, we determined the nucleotide (nt)
      sequence of the precore/core gene coding region and X gene region of the HBV DNA
      sequence in 7 subjects who were positive for HBs antigen and negative for HBc
      antibody. HBV DNA was detected by nested polymerase chain reaction (PCR). Nested
      PCR was carried out to amplify the precore/core and X open reading frames (ORFs)
      of HBV DNA. The second PCR products were sequenced, followed by investigation of
      nt homology. There were no deletions nor insertions in the nt sequence of the
      precore/core and X ORFs in the HBV DNA of these 7 patients, and mutations were
      found only sporadically in the 7 patients. Also, there were no common amino acid
      substitutions in the examined regions of the amino acid sequence of HBV in the 7
      patients, and we could not find a common mutation in the examined regions of HBV
      DNA that could potentially contribute to the development of negativity for HBc
      antibody. Thus, it is suggested that negativity for HBc antibody in patients with
      HBV2 is due to an immune response abnormality in the host.

PMID- 11509888
TI  - Role of interleukin-18 in peripheral blood mononuclear cells infected with human
      herpes virus type 6.
AB  - OBJECTIVE: Interleukin 18 (IL-18) production represents a critical step in the
      polarization of the Th1 immune response. Human herpes virus type 6 (HHV-6)
      possesses a peculiar tropism for immunocompetent cells. To understand the
      relationships among immunocompetent cells, HHV-6 and cytokines, the role of IL-18
      during infection of peripheral blood mononuclear cells (PBMC) with HHV-6 was
      evaluated. METHODS: PBMC were obtained from healthy HHV-6-seronegative donors,
      after centrifugation of heparinized venous blood over a Ficoll-Hypaque gradient.
      Supernatants from PBMC were analyzed for the presence of cytokines. To study the
      effects of exogenous recombinant human (rh) IL-18 on HHV-6 replication, the
      number of cells expressing viral antigens and the amount of extracellular virus
      were analysed. RESULTS: No basal production of IL-18 was found in supernatants of
      unstimulated PBMC. Appreciable amounts of the cytokine were produced by
      lipopolysaccharide (LPS)-stimulated PBMC. HHV-6 infection of LPS-treated PBMC
      downregulated IL-18 production. It was found that the addition of rhIL-18 to HHV
      6-infected PBMC downregulated the percentage of antigen-positive cells and the
      release of extracellular virus. CONCLUSION: Impairment of IL-18 release, which is
      involved in the induction of antiviral cytokines, such as interferon-gamma, could
      represent a strategy of the virus to evade the immune response of the host.

PMID- 11509889
TI  - Characterization of permanent cell lines that contain the AAV2 rep-cap genes on
      an Epstein-Barr-virus-based episomal plasmid.
AB  - Recombinant adeno-associated virus (rAAV) has emerged as a promising gene therapy
      vector. Its development, however, has been hampered by the lack of a readily
      available efficient production method. We investigated the possibility of
      establishing permanent cell lines for the production of rAAV with a new Epstein
      Barr-virus (EBV)-based episomal AAV rep-cap plasmid (pCEP-rep/cap). HeLa and 293
      cells were stably transfected with plasmids that carry the AAV2 rep/cap genes
      under transcriptional control of their endogenous promoters (p5, p19 and p40)
      either on the pCEP-rep/cap or an integrated (pIM45) plasmid. For the ease of
      monitoring transgene expression in live cells, a rAAV vector expressing gfp (the
      green fluorescent protein gene, rAAV-gfp/neo) was used. Establishment of stable
      transfected cell lines with these plasmids proved feasible but their usefulness
      was limited because of their instability. Within 8-12 weeks after their
      establishment, stably transfected rep-cap cell lines invariably lost their
      function. In addition, the rAAV-gfp/neo vector we used was susceptible to
      mutation in stably transfected HeLa cells. Our observations demonstrate specific
      problems both at the level of rep/cap gene function and the rAAV genome that can
      occur with the establishment of rAAV production cell lines. These experiments
      should aid the further development of efficient rAAV production protocols.

PMID- 11509890
TI  - Interleukin-4 is needed for the infection of monocytes by human cytomegalovirus.
AB  - OBJECTIVE: We studied the ability of human cytomegalovirus (HCMV) to infect
      peripheral blood mononuclear cells (PBMC) pretreated with or without Th2-cytokine
      interleukin-4 (IL-4) in vitro. METHODS: Adherent cells and nonadherent cells were
      obtained from PBMC. We inoculated these cells with HCMV at concentrations ranging
      from 0 to 10 ng/ml of IL-4. Immediate-early antigen-1 (IE-1) and glycoprotein H
      (gH) mRNAs were detected using the reverse-transcription polymerase chain
      reaction. RESULTS: IE-1 and gH mRNAs could be detected in monocytes pretreated
      with IL-4. In contrast, no IE-1 mRNA was detected in monocytes pretreated without
      IL-4. We tested whether higher infectious titers could result in the infection of
      monocytes whether or not they were pretreated with IL-4. However, no IE-1 mRNA
      was detected in the monocytes not pretreated with IL-4. To elucidate how HCMV
      infected monocytes affect lung tissue, human embryonic lung fibroblasts MRC-5
      were cocultured with HCMV-infected monocytes. The cytopathic effects of HCMV were
      observed microscopically and was confirmed by direct immunoperoxidase staining
      with a human monoclonal antibody against the HCMV IE-1. CONCLUSION: Our data
      strongly suggest that the ability of HCMV to infect monocytes may correlate with
      the presence of IL-4.

PMID- 11509891
TI  - The changing culture related to the practice of psychiatry.

PMID- 11509892
TI  - Prevalence and clinical correlates of residual depressive symptoms in bipolar II
      disorder.
AB  - BACKGROUND: Most patients with unipolar and bipolar I disorder have residual
      symptoms, despite successful treatment. The appraisal of subsyndromal
      symptomatology has important implications for pathophysiological models of
      disease and relapse prevention. Residual symptoms in bipolar II disorder were
      studied insufficiently. The study of residual symptoms in bipolar II disorder is
      important, because many depressed outpatients may suffer from it and because
      bipolar II disorder may be distinct from type I. The study aims were to assess
      the prevalence and clinical correlates of persistent residual depressive symptoms
      in bipolar II disorder. METHODS: 138 consecutive patients with bipolar II
      disorder and 83 unipolar disorder outpatients, presenting for major depressive
      episode treatment in private practice, were interviewed with the Structured
      Clinical Interview for DSM-IV Axis I Disorders - Clinician's Version. Study
      variables were persistent (more than 2 years) residual depressive symptoms, age,
      gender, age at onset, illness duration, recurrences, axis I comorbidity,
      severity, psychotic, melancholic and atypical features. RESULTS: The prevalence
      of residual depressive symptoms was 44.9% in bipolar II disorder and 43.3% in
      unipolar disorder. Residual depressive symptoms in bipolar II and unipolar
      disorders were significantly and positively associated with illness duration and
      recurrences. CONCLUSIONS: Persistent residual depressive symptoms were common in
      bipolar II disorder. Residual unipolar and bipolar II depressive symptoms were
      related to duration of illness and number of recurrences. Reducing these
      variables could reduce and prevent residual symptoms. A mechanism of kindling
      (more mood episodes leading to worse outcome) could be that of leaving a larger
      and larger amount of residual symptoms after the acute episode has subsided.

PMID- 11509893
TI  - A twin study of alexithymia.
AB  - BACKGROUND: Factors contributing to the development of alexithymia and the nature
      of alexithymia's relation with trait negative and positive affectivity are
      unclear. In this study, a twin approach was used to examine the degree of genetic
      and environmental contributions to the different facets of alexithymia, and the
      nature of their relations to trait negative and positive affectivity. METHOD:
      Forty-five monozygotic and 32 same-sex dizygotic twin pairs completed the Toronto
      Alexithymia Scale-20, the Eysenck Personality Inventory, and a zygosity
      questionnaire. RESULTS: Model fitting analyses indicated that familial influences
      contributed significantly to all three facets of alexithymia. Parameter estimates
      and intraclass correlations suggested, though could not confirm, that it was
      shared environmental factors that contributed to difficulty identifying and
      communicating emotions (ID and COM), but shared genetic factors that contributed
      to externally oriented thinking (EOT). Between-twin cross-trait twin analyses
      revealed strong correlations between ID and neuroticism, and between COM and
      extraversion, and suggested that it is shared familial influences which account
      for these associations. CONCLUSIONS: The results of this study indicate that: (a)
      the different facets of alexithymia are influenced by familial factors; (b) the
      previously noted associations between ID and COM and trait affectivity are not
      merely methodological artifacts; and (c) the associations between ID and COM and
      trait affectivity are influenced by familial factors. The results also suggest
      that ID and COM are largely influenced by shared environmental factors, but that
      EOT is influenced by genetic factors.

PMID- 11509894
TI  - Why do alexithymic features appear to be stable? A 12-month follow-up study of a
      general population.
AB  - BACKGROUND: This 12-month follow-up study investigated the prevalence of
      alexithymia and its relationship with depression in a sample of the general
      population from Eastern Finland (n = 1,584). METHODS: Alexithymia was assessed
      using the 20-item version of the Toronto Alexithymia Scale (TAS) and depression
      using the 21-item Beck Depression Inventory (BDI). RESULTS: The prevalence of
      alexithymia in each study phase was similar (baseline: 9.7%; follow-up: 10.1%).
      Mean values of BDI, TAS-20 and subfactors of the TAS-20 also remained unchanged
      between the study phases. However, by using the original cutoff points, we found
      that a proportion of the subjects were in a different TAS-20 category on follow
      up than at baseline. The mean values of BDI had not changed in those subjects who
      had similar alexithymia status in both phases, but increased or decreased in
      parallel with the change in TAS-20 score among all other subjects. CONCLUSIONS:
      Our findings indicate that it is important to use a variety of viewpoints when
      studying changes in alexithymia status. Alexithymia appears to be a stable trait
      based on the similarity of the mean TAS-20 scores in separate study phases.
      However, when focusing on the changes in alexithymia status at the individual
      level, alexithymic features also appear to be state dependent and strongly
      related to depressive symptoms.

PMID- 11509895
TI  - An evaluation of the absolute and relative stability of alexithymia in patients
      with major depression.
AB  - BACKGROUND: Previous studies demonstrating an association between alexithymia and
      depression have led to the proposal that alexithymia may be a state-dependent
      phenomenon rather than a stable and enduring personality trait. Several
      longitudinal studies have provided support for a trait view of alexithymia, but
      most of these studies evaluated absolute stability only (i.e., the extent to
      which alexithymia scores change over time) and did not examine the relative
      stability of alexithymia (i.e., the extent to which relative differences among
      individuals remain the same over time) in the context of changes in illness
      symptomatology. The present study evaluated both absolute stability and relative
      stability of alexithymia in depressed patients who experienced a marked reduction
      in the severity of depressive symptoms. METHODS: Forty-six psychiatric
      outpatients with major depression were assessed for alexithymia and depression
      with the 20-item Toronto Alexithymia Scale and the Hamilton Rating Scale for
      Depression at the start of treatment (baseline) and after 14 weeks of treatment
      (follow-up) with antidepressant medication. Paired t tests and correlational
      analyses were performed to evaluate absolute stability and relative stability in
      alexithymia. Hierarchical regression analyses were then used to assess the degree
      to which the relative stability in alexithymia scores was related to the severity
      of depressive symptoms, and the degree to which changes in alexithymia scores
      could be attributed to changes in depression scores. RESULTS: Alexithymia scores
      changed significantly from baseline to follow-up, indicating a general lack of
      absolute stability. There was, however, strong evidence of relative stability, as
      alexithymia scores at baseline correlated significantly with alexithymia scores
      at follow-up and were also a significant predictor of follow-up alexithymia
      scores, after partialling the effects of depression severity. CONCLUSIONS:
      Although alexithymia scores may change in the presence of large changes in the
      severity of depressive symptoms, the finding of relative stability of alexithymia
      supports the view that this construct is a stable personality trait rather a
      state-dependent phenomenon.

PMID- 11509896
TI  - Alexithymia and the temperament and character model of personality.
AB  - OBJECTIVE: In our study we explored the associations between alexithymia (Toronto
      Alexithymia Scale 20, TAS-20) and the dimensions and subscales of Cloninger's
      theoretically based and empirically validated psychobiological model of
      personality to further clarify the relationship between alexithymia and
      personality traits. METHODS: Psychiatric in- and outpatients (n = 254) were
      investigated with the TAS-20, the Temperament and Character Inventory (TCI) and
      the Symptom Check List SCL-90-R to control for the severity of current
      psychopathology. Correlation and regression analyses were performed. RESULTS: The
      regression analysis identified the TCI dimensions low self-directedness (SD), low
      reward dependence (RD) and to a minor degree harm avoidance (HA) as independent
      predictors for alexithymia. At the level of subscales, interpersonal detachment
      (RD3), low resourcefulness (SD3), low responsibility and blaming (SD1) and
      shyness with strangers (HA3) were predictors for alexithymia. The degree of
      explained variance of the TAS-20 scores by the TCI dimensions and subscales
      ranged between 43 and 45% whereas the inclusion of the general severity index
      into the regression models accounted for an additional 5% of the variance.
      CONCLUSIONS: Alexithymia is best explained by a mixture across different
      dimensions and subscales within Cloninger's psychobiological model of
      personality. However, alexithymia is captured only partly by current concepts of
      personality, and additional contributing psychological and biological factors
      need to be identified to understand alexithymia more extensively.

PMID- 11509897
TI  - Stress markers in relation to job strain in human service organizations.
AB  - BACKGROUND: Workers in human service organizations are often confronted with
      conflicting demands in providing care or education. The aim of this cross
      sectional study was to relate levels of endocrine stress markers to perceived job
      strain in two human service organizations. METHODS: Employees in two local units
      of the social insurance organization and two local units of the individual and
      family care sections of the social welfare in Sweden were selected and 103
      employees participated (56% participation rate). The perceived job strain was
      assessed with a standardized questionnaire containing questions of the demand
      control model. Questions specially designed to measure emotional demands were
      also included. The stress markers cortisol, prolactin, thyroid-stimulating
      hormone, testosterone and IgA and IgG were analysed in blood samples. RESULTS:
      The main finding was an association between high emotional strain and increased
      levels of prolactin. The levels of cortisol, but none of the other four stress
      markers, increased slightly with emotional strain. CONCLUSIONS: Emotional strain
      experienced in human service work may cause psychological stress. The increase in
      prolactin was modest but consistent with findings in other published studies on
      stress-related endocrine alterations.

PMID- 11509898
TI  - A follow-up study of psychiatric consultations in the general hospital: What
      happens to patients after discharge?
AB  - BACKGROUND: An appropriate follow-up is considered essential in the consultation
      liaison psychiatry setting, but it is often neglected. This study evaluated the
      effectiveness of the psychiatric consultation process in the general hospital, by
      investigating what occurred to patients 3-5 months after discharge. METHODS: We
      used a three-part questionnaire: (1) the results of the consultation process; (2)
      a telephone interview with patients, and (3) a telephone interview with the
      patients' primary care physician, to whom the patients were referred after
      discharge from hospital. We contacted all consecutive, unselected patients
      referred to psychiatric consultation from January to July 1999. Complete data
      were available for 119 patients from an initial group of 318. RESULTS: The
      consultation process was well accepted by patients and useful to general hospital
      physicians to complete the final diagnosis of the patient when discharged from
      hospital. In most cases (78.9%), the psychiatric letter was attached to the
      discharge letter. The second part of the questionnaire indicated that most
      patients were satisfied with the consultation process. They thought it helped
      focus their problems and 60% asserted that they felt better after following their
      psychiatrists' instructions or therapy. The primary care physicians agreed with
      the diagnostic results of the psychiatric consultation, mainly followed the
      psychiatrists' advice, and generally expressed positive comments about the
      consultation-liaison service. CONCLUSIONS: Compliance of hospital physicians,
      patients, and primary care physicians was good. Follow-up studies on outcome of
      psychiatric consultations are few and further analysis is strongly recommended.

PMID- 11509900
TI  - Ultrastructure of the human stratum corneum.
AB  - The ultrastructural study of the intercellular spaces of the human stratum
      corneum was based on transmission electron microscopy of thin vertical sections
      and freeze-fracture replicas, field emission scanning electron microscopy and
      immunofluorescence confocal laser scanning microscopy. The maturation of the
      corneosomes and their enzymatic degradation could be depicted at strategic
      interfaces. These sharp and rapid metamorphoses are now relatively well
      understood from a morphological point of view. But morphology raises a lot of
      unsolved physiological problems.

PMID- 11509901
TI  - Differences in corneocyte surface area in pre- and post-menopausal women.
      Assessment with the noninvasive videomicroscopic imaging of corneocytes method
      (VIC) under basal conditions.
AB  - The differences between pre- and postmenopausal women and men on corneocyte
      surface area were investigated by a noninvasive exfoliation method. Surface
      corneocytes were collected with a modified detergent scrub technique. Separated
      corneocytes were analyzed by videomicroscopy and image analyses (NIH Image 1.59).
      Additionally transepidermal water loss (TEWL) and stratum corneum hydration,
      water-holding capacity and moisture accumulation velocity were measured. 21
      postmenopausal females without hormonal substitution (age 50.6 years), 33
      premenopausal women (age 41.0 years) and 25 men matched for age (age 44.0 years)
      were included in this study. The smallest corneocyte surface area was seen in
      premenopausal women (368.0 pixels). For postmenopausal women and the male control
      population almost equal values could be detected (postmenopausal women 401.1
      pixels; men 401.8 pixels). Significant differences were calculated with the ANOVA
      test (p = 0.0050) and post-hoc analyses (Dunn test); premenopausal vs.
      postmenopausal women (p < 0.05) and premenopausal women vs. men (p < 0.05), but
      not postmenopausal women vs. men (p > 0.05). No statistically significant
      differences could be detected for TEWL, stratum corneum hydration parameters. No
      correlation could be found between the corneocyte surface area and barrier or
      hydration parameters. The detected differences support the hypothesis that sexual
      hormones have an impact on corneocyte surface area, because sex hormone levels
      are higher in premenopausal women than in non-hormone-substituted postmenopausal
      women or men.

PMID- 11509902
TI  - Investigation of follicular penetration of topically applied substances.
AB  - The influence of specific follicle properties, sebum production and hair growth
      on the follicular penetration of topically applied substances was investigated.
      The behavior of follicles identified in selected skin areas of volunteers was
      analyzed by various tape stripping and staining methods in combination with laser
      scanning microscopy. Furthermore hair growth in the selected skin areas was
      determined. A correlation between sebum production, hair growth activity and
      follicular penetration was observed.

PMID- 11509903
TI  - The role of follicular penetration. A differential view.
AB  - Textbooks describe percutaneous absorption through normal skin as diffusion
      through the stratum corneum barrier, i.e., in a simplified view, as a
      physiochemical interaction of a penetrating compound with the horizontal
      multilayer lipid structures and the underlying corneocytes within the horny
      layer. Hair follicles and sweat glands are vertical structures and are considered
      of little importance since 'they represent a small and insignificant percentage
      of the skin surface'. To this integral view, a differentiated hypothesis is
      proposed: the more perfect the barrier function of the horny layer, the greater
      the relative role of the imperfections within the skin as a defence organ. Three
      kinds of imperfections should be taken into account: (1) the follicular apparatus
      of hair follicles; (2) the sweat glands, and (3) microlesions in the
      interfollicular horny layer. Each of these can theoretically represent a vertical
      pathway for percutaneous absorption, i.e. a 'shunt'.

PMID- 11509904
TI  - Coordinate regulation of epidermal differentiation and barrier homeostasis.

PMID- 11509905
TI  - Iontophoretic transport across the skin.
AB  - There have been many attempts to define the key relationships between passive
      drug diffusion across the skin and the molecular and physicochemical properties
      of the permeant. At the present time, the importance of lipophilicity (or
      hydrogen bond donor and acceptor properties) and of molecular volume are well
      established, and useful predictive relationships for passive percutaneous
      permeability exist. With respect to iontophoresis, on the other hand, the
      situation is far less clear and the mechanisms involved have not been completely
      defined. The roles of electromigration and electroosmosis (current-induced
      convective solvent flow) are now beginning to be understood and experimentally
      separated. In turn, this allows the manner in which certain physicochemical
      parameters influence the efficiency of drug electrotransport to be deduced. An
      initial examination of a database drawn from the literature and from our own work
      (for which the experimental conditions employed were reasonably constant)
      suggests a rather sharp dependence of cationic drug delivery via electromigration
      upon molecular size. We suggest that the analysis reveals useful paths for
      further investigation.

PMID- 11509906
TI  - On the use of Micro-Imager to directly visualize drug distribution in human skin.
AB  - Knowledge of drug distribution into the skin has always been considered as a key
      parameter of both safety and efficiency. We describe here the use of a new and
      powerful device to directly visualize and quantify the skin distribution of a
      radioactively labelled compound on histological sections.

PMID- 11509907
TI  - Development of a low-metal adhesive tape to detect and localize metals in or on
      the stratum corneum at parts per million levels.
AB  - Tape-stripping is a well-established method for sampling the stratum corneum
      (SC). We have developed a tape with low-metal content suitable for use with
      particle-induced X-ray emission (PIXE), an analytical technique based on X-ray
      spectrometry. PIXE analysis of tape-stripped samples of SC is a reliable and
      minimally invasive means of identifying and quantifying metals present at parts
      per million levels. Assay feasibility and reproducibility was demonstrated using
      human volunteers. This new tape-strip technique has potential applications in
      exposure and decontamination assessment, diagnosis of metal dermatitis,
      forensics, and in environmental research.

PMID- 11509908
TI  - New aspects of the skin barrier organization.
AB  - In the superficial layer of the skin, the stratum corneum (SC), the lipids form
      two crystalline lamellar phases with periodicities of 6.4 and 13.4 nm (long
      periodicity phase). The main lipid classes in SC are ceramides, free fatty acids
      and cholesterol. Studies with mixtures prepared with isolated ceramides revealed
      that cholesterol and ceramides are very important for the formation of the
      lamellar phases, and the presence of ceramide 1 is crucial for the formation of
      the long-periodicity phase. This observation and the broad-narrow-broad sequence
      of lipid layers in the 13.4-nm phase led us to propose a molecular model for this
      phase. This consists of one narrow central lipid layer with fluid domains on both
      sides of a broad layer with a crystalline structure. This model is referred to as
      'the sandwich model'. While the presence of free fatty acids does not
      substantially affect the lipid lamellar organization, it is crucial for the
      formation of the orthorhombic sublattice, since the addition of free fatty acids
      to cholesterol/ceramide mixtures results in transition from a hexagonal to a
      crystalline lipid phase. Studies examining lipid organization in SC derived from
      dry or lamellar X-linked ichthyosis skin revealed that in native tissue the role
      of ceramide 1 and free fatty acids is similar to that observed with mixtures
      prepared with isolated SC lipids. From this we conclude that the results obtained
      with lipid mixtures can be used to predict the SC lipid organization in native
      tissue.

PMID- 11509909
TI  - Barrier function in reconstructed epidermis and its resemblance to native human
      skin.
AB  - One of the prerequisites for the use of human skin equivalents for scientific and
      screening purposes is that their barrier function is similar to that of native
      skin. Using human epidermis reconstructed on de-epidermized dermis we
      demonstrated that the formation of the stratum corneum (SC) barrier in vitro
      proceeds similarly as in vivo as judged from the extensive production of lamellar
      bodies, their complete extrusion at the stratum granulosum/SC interface, and the
      formation of multiple broad lamellar structures in the intercorneocyte space. The
      presence of well-ordered lipid lamellar phases was confirmed by small-angle X-ray
      diffraction. Although the long periodicity lamellar phase was present in both the
      native and the reconstructed epidermis, the short periodicity lamellar phase was
      present only in native tissue. In addition, the SC lipids predominantly formed
      the hexagonal sublattice. Analysis of lipid composition revealed that all SC
      lipids are synthesized in vitro. Differences in SC lipid organization in
      reconstructed epidermis may be ascribed to the differences in fatty acid content
      and profile indicating that further improvement in culture conditions is required
      for generation of in vitro reconstructed epidermis with stratum barrier
      properties of the native tissue.

PMID- 11509910
TI  - Modulation of the barrier function of the skin.
AB  - Transport of xenobiotics across the stratum corneum, the rate-controlling
      membrane of skin, is slow and the mechanism appears complex. However, the basic
      transfer is controlled by fundamental physicochemical concepts, the predominant
      of which are partition (K), diffusion (D) and solubility (C(s)). In order to
      change the rate of penetration it is therefore clear that it is these parameters
      that should be targeted. In most instances enhancement strategies are adopted to
      improve D, K or C(s), however there are instances in which permeation reduction
      may be beneficial. Examples include the topical application of sunscreens or
      insect repellents. This publication demonstrates the way in which modulation
      effects can be assessed and the difficulties involved in determining which of the
      physicochemical parameter(s) are being affected. If the formulation influences
      more than one, synergism can often be seen. Advances in computer modelling have
      provided an insight into the mechanisms of action of some of the chemical
      enhancers at a molecular level. Enhanced skin absorption has been reported for
      the delivery of macromolecules such as insulin (associated with transfersomes) or
      DNA (as a DOTAP complex). The barrier property of the skin must be modulated for
      this to be achieved. However the precise mechanisms of action have not been
      elucidated.

PMID- 11509911
TI  - Assessment of topical bioavailability in vivo: the importance of stratum corneum
      thickness.
AB  - We present a method to determine the cutaneous bioavailability and hence to
      evaluate the bioequivalence of topically applied drugs in vivo. The procedure
      uses serial tape-stripping and transepidermal water loss measurements to quantify
      the thickness of the removed stratum corneum (SC) and to determine the intact
      membrane thickness. Following tape-stripping, the drug is extracted from the
      tapes and assayed, e.g., by HPLC. This provides a drug concentration profile as a
      function of the normalized position within the SC. The data are fitted to a
      solution of Fick's second law of diffusion in order to calculate characteristic
      membrane transport parameters. Integration of the concentration profile over the
      entire SC thickness, that is, the 'area-under-the-curve', provides a measure of
      the cutaneous bioavailability and hence can be used to assess the bioequivalence
      of topically applied drugs.

PMID- 11509912
TI  - Oxidative targets in the stratum corneum. A new basis for antioxidative
      strategies.
AB  - As the outermost layer of skin, the stratum corneum (SC) is continuously exposed
      to an oxidative environment, including air pollutants, ultraviolet radiation,
      chemical oxidants, and aerobic microorganisms. Human SC reveals characteristic
      antioxidant and protein oxidation gradients with increasing antioxidant depletion
      and protein oxidation towards the outer layers. SC antioxidants, lipids, and
      proteins are oxidatively modified upon treatments with ultraviolet A/ultraviolet
      B, ozone, and benzoyl peroxide. alpha-Tocopherol represents the predominating SC
      antioxidant with respect to its concentration and its unique susceptibility to
      the various oxidative challenges tested. In sites rich in sebaceous glands, alpha
      tocopherol is physiologically delivered to the surface via secretion of sebum.
      Oxidative damage in the human SC represents an early pathophysiological event
      preceding barrier disruption and inflammation in environmentally challenged skin.
      Furthermore, oxidative gradients in SC proteins may have implications for the
      process of desquamation in human skin.

PMID- 11509913
TI  - The human stratum corneum layer: an effective barrier against dermal uptake of
      different forms of topically applied micronised titanium dioxide.
AB  - Electron microscopy visualisation and light microscopic investigations of three
      different application forms of titanium dioxide proved that neither surface
      characteristics, particle size nor shape of the micronised titanium dioxide
      result in any dermal absorption of this substance: Micronised titanium dioxide is
      solely deposited on the outermost surface of the stratum corneum and cannot be
      detected in deeper stratum corneum layers, the human epidermis and dermis.

PMID- 11509914
TI  - Correlation of the local distribution of topically applied substances inside the
      stratum corneum determined by tape-stripping to differences in bioavailability.
AB  - Tape-stripping and optical spectroscopy are used as a suitable combined method to
      determine the horny layer profile. Firstly, typical ultraviolet filter substances
      are used as active substances which are fixed inside the horny layer. Secondly,
      clobetasol propionate was applied topically in two formulations, Temovate Cream
      and Temovate and Emollient. The measured changes in the local distribution of the
      drug inside stratum corneum reflect the observed differences in the biological
      response visualized as blanching. The concentration of the drug in deeper parts
      of the horny layer proposes the existence of a small channel available for the
      percutaneous absorption. The observed low intensity blanching is correlated to
      the follicle orifices of the skin. After application of Temovate and Emollient, a
      lateral spreading of the drug must be taken into account.

PMID- 11509916
TI  - CIBIS, MERIT-HF, and COPERNICUS trial outcomes: do they complete the chapter on
      beta-adrenergic blockers as antiarrhythmic and antifibrillatory drugs?

PMID- 11509915
TI  - Changes in Thy1 gene expression associated with damaged retinal ganglion cells.
AB  - PURPOSE: The temporal series of molecular events that occur in dying retinal
      ganglion cells is poorly understood. We have examined the change in expression of
      a normally-expressed ganglion cell marker gene, Thy1, relative to the kinetics of
      cell loss caused by acute and chronic damaging stimuli. METHODS: For acute
      experiments, mice were subjected to optic nerve crush or intravitreal injections
      of N-methyl-D-aspartate (NMDA) to induce ganglion cell death. RNase protection
      analysis was used to quantify Thy1 mRNA levels from total retina RNA and in situ
      hybridization was used to monitor the pattern of Thy1 positive cells. Changes in
      Thy1 expression were compared to the time course of cell loss induced by each
      treatment. To induce elevated intraocular pressure (IOP), the episcleral veins of
      rats were injected with hypertonic saline, which scleroses Schlemm's Canal and
      the trabecular meshwork. Elevated IOP was monitored every day for 35 days after
      which the animals were sacrificed and the retinas harvested for quantitative RT
      PCR or fixed for in situ hybridization studies. Evaluation of glaucomatous damage
      caused by elevated IOP was determined from histological sections of the optic
      nerves of all rat eyes. RESULTS: After optic nerve crush, Thy1 mRNA levels
      decreased within 24 h, although the number of expressing cells did not decline
      until 7 days. Both measures showed a loss of Thy1 well in advance of cell loss,
      which was detected by 2 weeks after surgery. This change in expression was not
      dependent on execution of the cell death program since a similar decrease was
      detected in Bax-/- ganglion cells, which are resistant to cell death induced by
      optic nerve crush. Thy1 mRNA levels and the number of expressing cells also
      decreased within 6 h after NMDA injection, in advance of cell loss, which was
      detected by 24 h. Similarly, elevated intraocular pressure was associated with a
      decrease in mRNA and expressing cells in a pressure-dependent manner. In
      moderately hypertensive rat eyes, the number of cells expressing Thy1 decreased
      before significant cell loss in the retina. Virtually no Thy1-expressing cells
      were detected in eyes with severe disease. CONCLUSIONS: Thy1 mRNA abundance and
      expressing cells, decreased in advance of detectable ganglion cell loss caused by
      three different modalities of damage. This change is independent of the committed
      step of cell death.

PMID- 11509917
TI  - Importance of QT interval determination and renal function assessment during
      antiarrhythmic drug therapy.
AB  - A major concern associated with the use of antiarrhythmic drugs (AAD) is the
      occurrence of ventricular proarrhythmia, especially torsade de pointes (TdP). The
      AADs associated with TdP most commonly include quinidine, procainamide,
      disopyramide, sotalol, and the newer class III agents, such as ibutilide and
      dofetilide. It is not simply the administration and nature of an AAD but also
      several additional factors such as heart rate, ventricular hypertrophy,
      congestive heart failure, gender, age, concomitant drugs, and impaired drug
      clearance that influence TdP development. Dosing of these agents should be
      adjusted to take such factors into account to minimize the incidence of
      proarrhythmia.

PMID- 11509918
TI  - L-arginine improves post-ischemic vasodilation in coronary heart disease patients
      taking vasodilating drugs.
AB  - BACKGROUND: The hypothesis that intravenous L-arginine infusion improves the
      vasodilatory response to ischemia in the resistance vessels of human lower limbs
      in relatively young coronary heart disease patients taking vasodilating drugs was
      tested. METHODS: Twenty patients with onset of symptoms of coronary artery
      disease before age 50, operated for aortocoronary bypass and taking vasodilating
      drugs, were compared with 20 control subjects of comparable age and gender;
      neither group included heavy smokers (>10 cigarettes/day). Blood flow in the
      lower limbs was measured noninvasively with strain-gauge plethysmography, both at
      rest and during a reactive hyperemia test. Intravenous infusion of L-arginine was
      performed in nine coronary heart disease patients and in nine control subjects.
      RESULTS: Resting blood flow to the lower limbs was 2.3 mL/min/100 mL in control
      subjects vs 3.4 mL/min/100 mL in patients (difference not statistically
      significant). Peak blood flow measured after a 3-minute arterial occlusion was
      24.0 mL/min/100 mL in control subjects vs 20.3 mL/min/100 mL in coronary heart
      disease patients (P<0.05). Peripheral minimal vascular resistances were 4.28 and
      5.46 peripheral resistances units (p.r.u.) in control subjects and patients,
      respectively (P<0.05). Intravenous infusion of L-arginine was followed by
      increased resting blood flow in cases and controls (P=0.009), with a parallel
      reduction in peripheral resting vascular resistances (P=0.009). Coronary heart
      disease patients showed increased peak blood flow (P=0.04) and reduced minimal
      vascular resistances (P=0.02), whereas no statistically significant changes in
      these parameters were detectable in control subjects. Intravenous glucose
      infusion, leading to increased serum insulin concentration, did not modify any
      hemodynamic parameter. CONCLUSIONS: Hemodynamic responses in the skeletal muscle
      are impaired during a reactive hyperemia test in relatively young coronary heart
      disease patients taking vasodilating drugs. Intravenous L-arginine infusion
      corrects the impaired vasodilatory response of the lower limbs to an acute
      increase in flow following a cuff thigh occlusion.

PMID- 11509919
TI  - The relationship between low-density lipoprotein cholesterol goal attainment and
      prevention of coronary heart disease--related events.
AB  - BACKGROUND: According to the National Cholesterol Education Program (NCEP)
      treatment guidelines, patients with preexisting coronary heart disease (CHD) or
      other atherosclerotic vascular disease should lower low-density lipoprotein (LDL)
      cholesterol to < or = 100 mg/dL. Recent statin trials document the benefit of
      cholesterol lowering on CHD events but do not address the optimal goal of LDL
      cholesterol. METHODS: The pravastatin to simvastatin conversion-lipid
      optimization program (PSCOP) at the VA San Diego Healthcare System (VASDHS) was a
      formulary-conversion program designed to increase the percentage of patients who
      meet their recommended NCEP LDL cholesterol goal. We compared the incidence of
      clinical outcome and mortality between CHD patients from the original PSCOP
      cohort with postconversion LDL cholesterol greater than and < or = 100 mg/dL. A
      total of 524 patients were stratified by postconversion LDL cholesterol levels
      (greater than [N=183]) or < or = 100 mg/dL [N=341]) and observed for a mean
      duration of 27.7 months. Patients' VASDHS records were reviewed for
      postconversion mortality from any cause and CHD-related events. Patients were
      mailed a questionnaire to capture similar events that may have occurred outside
      of VASDHS, which might not be present in the patient's VASDHS record. RESULTS:
      Lipid-lowering therapy < or = 100 mg/dL was associated with a significantly lower
      percentage of total deaths and CHD-related events (40% vs 61%, P=0.008). In
      patients with LDL cholesterol >100 mg/dL, the relative risk of unstable angina
      (relative risk, 2.2; 95% confidence interval, 1.3 to 3.8; P=0.004) and stroke
      (relative risk, 3.0; 95% confidence interval, 1.04 to 8.6; P=0.04) were
      significantly greater compared to patients meeting their LDL cholesterol goal.
      CONCLUSIONS: Our study results support reducing LDL cholesterol to at least 100
      mg/dL in the patient with CHD.

PMID- 11509920
TI  - Dose dependency of fluvastatin pharmacokinetics in serum determined by reversed
      phase HPLC.
AB  - BACKGROUND: Fluvastatin is an inhibitor of the 3-hydroxy-3-methylglutaryl
      coenzyme A (HMG-CoA) reductase, effectively lowering serum cholesterol
      concentrations. A high-performance liquid chromatography (HPLC) assay was
      developed that determined the pharmacokinetics of fluvastatin in healthy
      individuals after administration of 40 and 80 mg fluvastatin. METHODS: The method
      was linear for serum concentrations between 10 ng/mL and 5,000 ng/mL, showing
      good coefficients of variations and sample stability. After administration of 40
      mg fluvastatin, the mean values of the area under the serum concentration vs time
      curve (AUC), the maximum serum drug concentration (C(max)), the time to reach
      C(max) (t(max)), and the serum elimination half-life time were 528.5 +/-358.8
      ng/mL x h, 149.6 +/-56.0 ng/mL, 60.0 +/-30.0 minutes, and 108.0 +/-67.9 minutes,
      respectively. The corresponding values for a dose of 80 mg fluvastatin were
      1417.7 +/-879.2 ng/mL x h, 1024.7 +/-1085.1 ng/mL, 60.0 +/-21.2 minutes, and
      106.0 +/-73.6 minutes, respectively. Doubling of the dose from 40 mg to 80 mg
      caused an overproportional increase of AUC and C(max). RESULTS AND CONCLUSION:
      Results suggest that the measurement of fluvastatin serum concentrations by means
      of HPLC provides reliable data within the broad range of physiological serum
      concentrations. The pharmacokinetic data after administration of high doses (80
      mg) showed an overproportional increase of AUC and C(max), suggesting a
      saturation of the hepatic first-pass effect. Thus, in patients treated with
      additional substances interfering with fluvastatin metabolism, fluvastatin serum
      concentrations should be analyzed.

PMID- 11509921
TI  - Renal artery stenosis in minority patients undergoing diagnostic cardiac
      catheterization: prevalence and risk factors.
AB  - BACKGROUND: Atherosclerotic renal artery stenosis (RAS) is a frequently
      overlooked clinical entity that can cause progressive renal failure and
      uncontrolled hypertension. Revascularization of a stenosed renal artery is
      associated with improved clinical outcomes including the prevention of renal
      failure. Thus, it is important to recognize all potential candidates for renal
      artery revascularization. In a general population referred for diagnostic cardiac
      catheterization, RAS of any severity was found in 30% of patients and significant
      stenosis (> or = 50% diameter narrowing) was found in 15% of patients. The number
      of minority groups is increasing in the US population, and RAS in this population
      is not well investigated. Our purpose was to determine the prevalence and risk
      factors associated with RAS in minority patients referred for diagnostic cardiac
      catheterization. METHODS: Abdominal aortography was performed in 171 consecutive
      minority patients referred for diagnostic cardiac catheterization (hispanics =
      115, African Americans = 56). The association of clinical and angiographic
      variables with RAS was examined using univariate and multivariate logistic
      regression analyses. RESULTS: Renal artery stenosis of any severity was
      identified in 13.5% of patients (unilateral 7.7%, bilateral 5.8%). Significant
      RAS was found in 7.7% of patients (unilateral 4.8%, bilateral 2.9%). Independent
      predictors of RAS included age (mean +/-1SD, 68 +/-10 vs 57 +/-12 yr, P < 0.001,
      for patients with vs without RAS), coronary artery disease, and elevated serum
      creatinine levels (> 115 micromol/L). Race/ethnicity (hispanics vs African
      Americans), sex, smoking, congestive heart failure, diabetes mellitus, peripheral
      vascular disease, and hypertension were not independent predictors. CONCLUSIONS:
      Renal artery stenosis in minority patients undergoing diagnostic cardiac
      catheterization is less common than reported in white patients, is similar in
      hispanics and African Americans, and is similar in women and men. The clinical
      and angiographic features are helpful in predicting its presence.

PMID- 11509922
TI  - Different isoforms of tocopherols enhance nitric oxide synthase phosphorylation
      and inhibit human platelet aggregation and lipid peroxidation: implications in
      therapy with vitamin E.
AB  - BACKGROUND: alpha-Tocopherol has received much attention in the primary and
      secondary prevention of coronary artery disease. Absence of other isoforms, such
      as gamma- and delta-tocopherol, in commercial preparations of vitamin E may
      account for the inconsistent results of clinical trials. Since platelet
      aggregation is intimately involved in thrombogenesis, the relative effects of
      alpha-, gamma-, and delta-tocopherol and their combination were examined on human
      platelet aggregation, lipid peroxidation, and constitutive nitric oxide synthase
      (cNOS) activity. METHODS AND RESULTS: Human platelets were incubated with the
      three different isoforms of tocopherol and their combination for 30 minutes, and
      then ADP-induced platelet aggregation measured. All three isoforms of tocopherol
      markedly and similarly decreased platelet aggregation in a concentration (120-
      480 microM)-dependent manner. All three tocopherols also decreased the level of
      the lipid peroxidation product, malondialdehyde (MDA), and increased NO release
      (P < 0.05 vs control). These isoforms of tocopherol did not affect cNOS protein
      expression, but enhanced cNOS phosphorylation in platelets. The combination of
      three tocopherols in a concentration found in nature was more potent than alpha-,
      gamma-, or delta-tocopherol alone in this regard. CONCLUSION: These observations
      suggest that all three major isoforms of tocopherol have a similar effect on
      human platelet aggregation. The three isoforms appear to attenuate platelet
      aggregation at least in part via a decrease in free radical generation and an
      increase in platelet cNOS activity. The combination of tocopherols has a
      synergistic platelet inhibitory effect. Future clinical trials should concentrate
      on the combination of these three isoforms of tocopherols.

PMID- 11509923
TI  - Heparin reacts with and inactivates nitric oxide.
AB  - Although heparin is a well-known anticoagulant, in some cases it promotes a
      prothrombotic state and does so through both antibody-dependent and antibody
      independent platelet activation. In this study, heparin was found to reverse the
      antiplatelet effect of an NO donor. S-nitroso-glutathione (SNO-Glu), with an
      EC(50) of 1.8 U/mL. Ultraviolet/visible spectral analysis and the Griess assay
      showed that increasing heparin concentrations on a dose-dependent basis
      eliminated acidified NO(x) species. Since heparin is a heterogeneous mixture of
      glycosaminoglycans, the effects of six different heparin disaccharides were
      compared with various substitutions on the hexose rings to determine which
      functional group(s) of the polysaccharide interact with acidified NO(x). Among
      the six disaccharides tested, only types I-S and II-S had the effect, suggesting
      that the sulfamino-group at the C2 position of the glucosamine moiety was
      critical for the elimination of acidified NO(x) species. Mass spectrometry
      experiments gave results consistent with these observations, indicating that only
      the I-S and II-S heparin disaccharides were modified upon treatment with
      NaNO(2)/HCl. Negative-ion electro-spray ionization MS and tandem MS analyses of
      the native compounds and their deuterium-labeled analogs confirmed that the
      reaction products from nitrosation of these N-sulfated disaccharides had
      eliminated the C2-sulfamino-moiety and replaced it with methoxide derived from
      the solvent. Participation of the 6-sulfato-substituent appears to facilitate the
      elimination reaction. These data show that heparin can impair the antiplatelet
      properties of nitric oxide by interacting with the nitrosating species, and
      suggest that heparin-like glycosamino-glycans may interact with endothelium
      derived nitric oxide in vivo to regulate the bioactivity of this important
      antiplatelet and vasorelaxant substance.

PMID- 11509924
TI  - Comparative effects of ACE inhibitors and an angiotensin receptor blocker on
      atherosclerosis and vascular function.
AB  - BACKGROUND: Both angiotensin-converting enzyme inhibitors (ACE-I(s)) and
      angiotensin receptor blockers (ARB(s)) provide vascular protection. This study
      was designed to compare ACE-I(s) with widely differing tissue affinity (captopril
      and quinapril) and an ARB (losartan) on vascular protection against the adverse
      effects of high cholesterol. METHODS AND RESULTS: Forty-two New Zealand rabbits
      on a 0.5% cholesterol diet were randomized into control, captopril (10 mg/kg/d),
      quinapril (0.3 mg/kg/d), and losartan (8 mg/kg/d) groups for 14 weeks. Captopril,
      quinapril, and losartan significantly attenuated aortic lipid lesions (P=0.001).
      Captopril and quinapril were more effective than losartan in preserving vascular
      relaxation. CONCLUSIONS: Captopril, quinapril, and losartan had similar
      protective effects against atherogenesis. Captopril and quinapril were more
      effective than losartan in preserving vascular function. Increased bradykinin by
      ACE inhibition may be responsible for this improved vascular endothelial
      function.

PMID- 11509925
TI  - Effect of chronic AT(1) receptor antagonism on postischemic functional recovery
      and AT(1)/AT(2) receptor proteins in isolated working rat hearts.
AB  - To determine whether chronic angiotensin II (Ang II) type I receptor (AT(1)R)
      antagonism improves recovery of left ventricular (LV) function after ischemia
      reperfusion (IR) and increases AT(1)R and Ang II type 2 receptor (AT(2)R) protein
      expression in isolated working rat hearts, rats were randomized to pretreatment
      with either losartan (30 mg/kg/day) or UP269-6 (3 mg/kg/day), or no drug
      (control), for 1 week or 3 weeks before IR (50 min perfusion, 25 min ischemia, 40
      min reperfusion). In vitro LV work and power and ex vivo AT(1)R and AT(2)R
      proteins (immunoblots) were measured. Compared to baseline perfusion, LV work and
      power showed variable recovery in control, losartan, and UP269-6 groups. Compared
      to control, losartan preserved recovery of LV work and power while UP269-6 showed
      less recovery after IR at both 1 week and 3 weeks. Both antagonists increased
      AT(2)R but not AT(1)R protein. The duration of pretreatment did not affect the
      expression of AT(1)R or AT(2)R proteins. The results indicate that chronic AT(1)R
      blockade over 1 or 3 weeks increases AT(2)R (not AT(1)R) protein expression and
      may preserve but not improve postischemic functional recovery compared to
      controls in isolated working rat hearts.

PMID- 11509926
TI  - Activation of ATP-sensitive potassium channels in hypoxic cardiac failure is not
      mediated by adenosine-1 receptors in the isolated rat heart.
AB  - BACKGROUND: Hypoxic cardiac failure is accompanied by action potential
      shortening, which in part might be a consequence of opening of cardiac ATP
      sensitive potassium channels (K(ATP) channels). Coupling of the adenosine-1
      receptor (A-1 receptor) to these channels has been described; however, the
      interaction of A-1-receptors and K(ATP) channels in different models of ischemia
      is still under debate. The hypothesis as to whether A-1 receptors are involved in
      hypoxic K(ATP) channel-activation in the saline-perfused rat heart was tested.
      METHODS AND RESULTS: Pharmacologic modulation of the K(ATP) channel by
      Glibenclamide (inhibitor) and Rimalkalim (activator) and of the A-1 receptor by
      R(-)-N6-(1-methyl-2-phenylethyl)-adenosine (R(-)-PIA, agonist) and 1,3-diethyl
      3,7-dihydro-8-phenyl-purine-2,6-dione (DPX, antagonist) at different oxygen
      tensions (95% O2 and 20% O2) was performed in isolated Langendorff-rat hearts.
      Peak systolic pressure (PSP, intraventricular balloon), duration of monophasic
      action potential (epicardial suction electrode, time to 67% of repolarization:
      MAP(67%)), coronary flow, and heart rate (HR) were registered. Hypoxic perfusion
      resulted in a significant reduction of PSP (from 106 +/-11 to 56 +/-8 mmHg, P <
      0.005) and shortening of MAP(67%) (from 37 +/-3 to 25 +/-4 ms, P < 0.005). With
      application of 1 microM Glibenclamide, MAP(67%) returned to normoxic values and
      PSP increased to 78 +/-9 mmHg (P < 0.005 vs hypoxia). In normoxia, 2 microM
      Rimalkalin resulted in reduction of MAP(67%) and PSP, which was reversed by
      Glibenclamide. Application of 0.1 microM R(-)-PIA in normoxia resulted in a
      decrease of HR (from 235 +/-36/min to 75 +/-41/min, P < 0.005), which was
      accompanied by an increase of PSP from 96 +/-7 to 126 +/-9 mmHg (P < 0.05)
      without changes in MAP(67%). These effects were reversible by 1 microM DPX and
      remained unaffected by application of 1 microM Glibenclamide. Application of 1
      microM DPX in hypoxia had no effect on the measured parameters. CONCLUSION: In
      isolated rat hearts, the K(ATP) channel-system is activated in hypoxic cardiac
      failure and contributes to action potential shortening and reduced contractile
      performance. These effects seem to be independent of the A-1 receptor in this
      model.

PMID- 11509927
TI  - Identification of a cardiac sodium channel insensitive to synthetic modulators.
AB  - BACKGROUND: DPI 201-106 (DPI) was the first synthetic compound showing
      cardioselective modulation of voltage-gated sodium channels (VGSCs) resulting in
      a positive inotropic effect. Currently, the exact mode of action for this class
      of compounds is not known. METHODS: Effects of different natural and synthetic
      sodium channel modulators were investigated in cardiac tissue of several species
      with conventional electrophysiologic methods. RESULTS: In electrically driven
      cardiac tissues, all compounds investigated increased force of contraction (FC)
      and action potential duration (APD) with increasing concentrations except for DPI
      in cattle trabecular muscle, which demonstrated no effect. Interestingly,
      calculation of EC50 levels at 30% repolarization demonstrates that natural VGSC
      ligands were highly potent in prolonging the APD in cattle whereas no positive
      trends could be obtained for DPI and SDZ 211-939 (SDZ) in cattle. CONCLUSIONS:
      These results demonstrate that the binding site for DPI and SDZ is distinct from
      sites 2 or 3 of the VGSC alpha-subunit. Moreover, this is the first time that
      these compounds show no effect or even shortening of APD. This finding will
      enable the characterization of the mode of action and probably the binding site
      for synthetic VGSC-modulators.

PMID- 11509928
TI  - Immunoregulatory role of chimerism in clinical organ transplantation.

PMID- 11509929
TI  - Chronic graft-versus-host disease: clinical manifestation and therapy.
AB  - Chronic graft-versus-host disease (GVHD) is a major cause of morbidity and
      mortality in long-term survivors of allogeneic stem cell transplantation. The
      immunopathogenesis of chronic GVHD is, in part, TH-2 mediated, resulting in a
      syndrome of immunodeficiency and an autoimmune disorder. The most important risk
      factor for chronic GVHD is prior history of acute GVHD and strategies that
      prevent acute GVHD also decrease the risk of chronic GVHD. Other important risk
      factors are the use of a non-T cell-depleted graft, and older age of donor and
      recipient. Whether recipients of peripheral blood stem cells are at increased
      risk of chronic GVHD remains unsettled. There are no known pharmacologic agents
      which can specifically prevent development of chronic GVHD. Agents which have
      efficacy in the treatment of autoimmune disorders have been utilized as therapy
      for established chronic GVHD and are associated with response rates of 20% to
      80%. Most responses are confined to skin, soft tissue, oral mucosa and
      occasionally liver. Bronchiolitis obliterans responds infrequently to therapy and
      is associated with a dismal prognosis. Newer, promising therapeutic strategies
      under investigation include thalidomide, photopheresis therapy, anti-tumor
      necrosis factor and B cell depletion with anti-CD20 monoclonal antibody.

PMID- 11509930
TI  - High-dose melphalan with autologous hematopoietic stem cell transplantation for
      acute myeloid leukemia: results of a retrospective analysis of the Italian
      Pediatric Group for Bone Marrow Transplantation.
AB  - This retrospective study from the Italian Association of Pediatric Hematology
      Oncology-Bone Marrow Transplant Group (AIEOP-TMO) reports the results of
      consolidation with high-dose melphalan and autologous hematopoietic stem cell
      transplantation (auto-HSCT) in patients with acute myeloid leukemia (AML) in
      first complete remission (CR1). From October 1994 to July 1999, 20 patients
      (median age 9.9 years, range 0.11-16.2) were treated in six centers. Eighteen had
      de novo AML and two had secondary AML. According to BFM criteria, 10 were
      classified as standard- and 10 as high-risk patients, respectively. The median
      time from diagnosis to CR1 and from diagnosis to Auto-HSCT were 1.1 months (range
      0.8-1.6) and 4.3 months (range 3.1-6.2), respectively. Purging with either
      mafosfamide (three) or in vivo interleukin-2 (four) was performed in seven of 20
      patients. Melphalan was administered at a dosage of 150-220 mg/m(2) (median 180).
      Median total number of nucleated cells infused was 2.5 x 10(8)/kg (range 1.1
      8.9). The myeloablative regimen was well tolerated with no toxic death, veno
      occlusive disease or life-threatening complications. All patients had
      hematopoietic recovery in a median time of 27 days for neutrophils and 44 days
      for platelets. Eight of 20 patients relapsed after a median time of 7.2 months
      from transplant (range 5.7-15.9). Six of them died (five of progression of
      disease and one of sepsis) while the remaining two patients are alive in CR2. The
      3-year cumulative probability of survival and event-free-survival (EFS) is 62%
      and 56%, respectively. This study showed that in pediatric patients with AML
      consolidation of CR1 with high-dose melphalan allows survival and EFS to be
      obtained comparable to other auto-HSCT or chemotherapy published series with a
      potential sparing effect both on duration of treatment (with respect to
      chemotherapy) and on long-term side-effects (with respect to auto-HSCT with TBI
      or busulfan containing regimens).

PMID- 11509931
TI  - Dexamethasone, paclitaxel, etoposide, cyclophosphamide (d-TEC) and G-CSF for stem
      cell mobilisation in multiple myeloma.
AB  - Forty-one patients with multiple myeloma were treated with a novel stem cell
      mobilisation regimen. The primary end points were adequate stem cell mobilising
      ability (>1% circulating CD34-positive cells) and collection (> or = 4 x 10(6)
      CD34-positive cells/kg), and safety. The secondary end point was activity against
      myeloma. The regimen (d-TEC) consisted of dexamethasone, paclitaxel 200 mg/m(2)
      i.v., etoposide 60 mg/kg i.v., cyclophosphamide 3 g/m(2) i.v., and G-CSF 5-10
      microg/kg/day i.v. A total of 84 cycles were administered to these 41
      individuals. Patient characteristics included a median age of 53 years, a median
      of five prior chemotherapy cycles, and a median interval of 10 months from
      diagnosis of myeloma to first cycle of d-TEC. Seventy-five percent of the
      patients had stage II or III disease, 50% had received carmustine and/or
      melphalan previously, and 25% had received prior radiation therapy. Eighty-eight
      percent of patients mobilised adequately after the first cycle of d-TEC and 91%
      mobilized adequately after the second cycle. An adequate number of stem cells
      were collected in 32 patients. Of the remaining nine patients, three mobilised,
      but stem cells were not collected, two mobilised but stem cell collection was < 4
      x 10(6) CD34-positive cells/kg, three did not mobilise, and one died of disease
      progression. Major toxicities included pancytopenia, alopecia, fever and
      stomatitis. One patient died from multi-organ failure and progressive disease.
      Fifty percent of evaluable patients demonstrated a partial response and 28.6% of
      patients had a minor response. This novel dose-intense regimen was safe, capable
      of stem cell mobilisation and collection, even in heavily pre-treated patients,
      and active against the underlying myeloma.

PMID- 11509932
TI  - Storage of unprocessed G-CSF-mobilized whole blood in a modified Leibovitz's L15
      medium preserves clonogenic capacity for at least 7 days.
AB  - Autologous stem cell transplantation using unprocessed, G-CSF-mobilized whole
      blood (WB) is a simple, cost-reducing procedure and supports high-dose
      chemotherapy regimens not exceeding 72 h. Thereafter, clonogenic capacity rapidly
      decreases if routine anticoagulants are used for storage. In order to increase
      clinical applicability, we investigated the requirements for optimal preservation
      of unprocessed WB for 7 days. During storage at 22 degrees C in CPDA-1, a
      decrease in pH was noted, which was at least partially responsible for the low
      recovery of clonogenic cells. Subsequently, WB cells were stored in various cell
      culture media (RPMI 1640, alpha-MEM, X-VIVO15, CellGro SCGM and Leibovitz's L15
      medium) containing either serum, serum-free substitutes or no additives.
      Leibovitz's L15 showed significantly better CFU-GM recoveries than the other
      media. Using a calcium-free modification of L15 medium (added 3:10 to WB), 94 +/-
      24% of CD34(+) cells, 41 +/- 14% of BFU-E, 56 +/- 17% CFU-GM and 90 +/- 14% of
      LTC-IC were preserved during storage for 7 days at 22 degrees C. Storage at 4
      degrees C was also feasible, but showed less optimal recoveries of 52 +/- 29%
      (CD34), 32 +/- 10% (BFU-E), 13 +/- 7% (CFU-GM) and 58 +/- 9% (LTC-IC). The
      expression of CD38, Thy-1, c-kit, AC133, L-selectin and CXCR4 on CD34-positive
      cells remained unchanged. In conclusion, a modified Leibovitz's L15 medium better
      meets the metabolic requirements of a high-density cell culture and allows safe
      storage of G-CSF mobilized WB for at least 7 days. The results encourage further
      exploration of WB transplants stored for 7 days for clinical use.

PMID- 11509933
TI  - Failure of sustained engraftment after non-myeloablative conditioning with low
      dose TBI and T cell-reduced allogeneic peripheral stem cell transplantation.
AB  - We investigated whether a T cell-reduced allogeneic stem cell transplant (SCT)
      with minimal conditioning and subsequent donor lymphocyte infusions (DLI) could
      reduce the incidence and severity of GVHD while retaining stable engraftment.
      Five patients with hematological malignancies (three MM, one CLL, one Chediak
      Higashi syndrome) were conditioned with TBI (200 cGy). One patient additionally
      received fludarabine (120 mg/m(2)). CsA and mofetyl-mycophenolate (MMF) were
      administered to prevent GVHD. All patients were grafted with >3 x 10(6)/kg highly
      purified CD34(+) cells together with 2 x 10(6)/kg CD3(+) cells (three patients)
      or 1 x 10(5)/kg CD3(+) cells (two patients). Quick hematopoietic recovery and
      initial mixed donor chimerism was observed. Treatment-related toxicity was
      minimal in all but one patient who died of treatment-refractory GVHD on day 112.
      The four other patients only achieved partial donor T cell chimerism. BM and PBMC
      donor chimerism was lost between day 40 and 209 despite DLI. Three patients are
      alive with disease and one is in CR. We conclude that T cell-reduced SCT using
      200 cGy as the conditioning regimen does not result in stable hematopoietic
      engraftment. Predominant donor T cell chimerism is not a prerequisite for initial
      allogeneic hematopoietic proliferation. However for sustained long-term
      engraftment it is of major importance.

PMID- 11509934
TI  - Similar myeloid recovery despite superior overall engraftment in NOD/SCID mice
      after transplantation of human CD34(+) cells from umbilical cord blood as
      compared to adult sources.
AB  - Umbilical cord blood (UCB), bone marrow (BM) and mobilized peripheral blood (mPB)
      are used as sources of hematopoietic stem cells for transplantation. The NOD/SCID
      mouse model was used to compare the lineage-specific repopulating potential of
      CD34(+) cells derived from these sources. Six to 8 weeks after transplantation,
      blood, BM, spleen, liver and thymus, were harvested, and analyzed by flow
      cytometry using CD34, CD45, myeloid, and lymphoid lineage-specific antibodies.
      Fifty percent engraftment of human cells in bone marrow of mice was estimated to
      be reached with 0.55 x 10(6) CD34(+) UCB cells or with 7.9 x 10(6) CD34(+) cells
      from adult sources, illustrating a 10-fold superiority of UCB CD34(+) cells to
      engraft NOD/SCID mice. Lineage-specific characterization of engrafted human cells
      showed that the high engraftment potential of CD34(+) cells from UCB was due to a
      preferential B cell development (2-81%). In contrast, comparable percentages of
      myeloid cells were found following transplantation of CD34(+) cells from UCB, BM
      and mPB (1-38%), and occurred at significant levels only at relatively high
      doses. Since the CD34 content of UCB transplants is usually at least one log
      lower than of transplant from adult sources, these results correspond to the
      clinical findings with UCB transplantation showing a relatively high overall
      engraftment, but delayed myeloid recovery.

PMID- 11509935
TI  - Phase II study of a multi-course high-dose chemotherapy regimen incorporating
      cyclophosphamide, thiotepa, and carboplatin in stage IV breast cancer.
AB  - The purpose of this study was to determine the feasibility and efficacy of
      multiple courses of high-dose cyclophosphamide, carboplatin and thiotepa with
      peripheral blood progenitor cell (PBPC) transplantation in women with advanced
      breast cancer. Forty-one patients with advanced hormone-refractory breast cancer
      were enrolled in the study. The treatment started with two courses of 5
      fluorouracil 500 mg/m(2), epirubicin 120 mg/m(2) and cyclophosphamide 500 mg/m(2)
      (FE(120)C) followed by PBPC harvesting. The high-dose regimen consisted of three
      subsequent courses of 'tiny' CTC, cyclophosphamide 4000 mg/m(2), thiotepa 320
      mg/m(2) and carboplatin 1060 mg/m(2) (target AUC 13.3 mg/ml/min) (tCTC) divided
      over 4 consecutive days. The second and third courses were scheduled to begin on
      day 28 after the previous transplantation. A total of 86 tCTC courses was given
      to 33 of the 41 enrolled patients. Major toxicities consisted of hemorrhagic
      cystitis (six patients), prolonged gastro-intestinal toxicity (three patients)
      and veno-occlusive disease (two patients). There was one therapy-related death
      (unknown cause). Twenty patients (49%) achieved a complete response, nine (22%) a
      partial response and three patients stable disease after treatment. The median
      follow-up of the surviving patients was 43 months (range 25-61). Six patients
      remain in complete remission beyond 3 years. At 4 years, the progression-free
      survival (PFS) and overall survival (OS) for the whole patient group were 23 and
      30% with a median duration of 12 and 27 months, respectively and for FE(120)C
      responsive patients 32 and 36%, respectively with a median duration of 15 and 33
      months. In the patient group with a PFS > or = 18 months all patients had limited
      disease (metastatic disease in only one or two sites) and fewer patients had bone
      or liver metastases compared to the overall patient group (33% vs 51%). This
      report shows that three closely spaced courses of tCTC are feasible, with
      acceptable toxicity. Triple tCTC can achieve complete or partial remission in
      most patients and long-term PFS in a selected subgroup of patients who have
      limited metastatic disease and are responsive to conventional-dose chemotherapy.

PMID- 11509936
TI  - Phase III study comparing tacrolimus (FK506) with cyclosporine for graft-versus
      host disease prophylaxis after allogeneic bone marrow transplantation.
AB  - We report the results of a phase III trial comparing tacrolimus (FK506) with
      cyclosporine for GVHD prophylaxis after allogeneic BMT. From February 1995 to
      July 1996, 136 patients were enrolled and followed up to September 1997. During
      the first 100 days post-transplant the incidence of grade II-IV acute GVHD (the
      primary end-point) was lower in the tacrolimus group (17.5%) compared with the
      cyclosporine group (48.0%, P < 0.0001). A significant difference was observed
      between the tacrolimus and cyclosporine groups when subset analyses were
      performed based on recipients from HLA-matched siblings (13.3% vs 41.3%, P =
      0.015) or donors other than HLA-matched siblings (21.4% vs 53.8%, P= 0.0029). The
      incidence of chronic GVHD (47.3% and 47.8%) and Kaplan-Meier estimate of overall
      survival (62.9% and 65.2%) were similar between the tacrolimus and cyclosporine
      groups, respectively. The overall leukemia relapse rate was not significantly
      different between the tacrolimus and cyclosporine groups (19.6% and 11.4%,
      respectively). However, the relapse rate among recipients from HLA-matched
      siblings was significantly higher in the tacrolimus group (30.9%) compared with
      the cyclosporine group (3.6%, P = 0.013). These results suggest the merit of
      tacrolimus for the prophylaxis of acute GVHD, but a lack of merit for a graft
      versus-leukemia effect among recipients from HLA-matched sibling donors.

PMID- 11509937
TI  - A multicenter, randomized, double-blind comparison of different doses of
      intravenous immunoglobulin for prevention of graft-versus-host disease and
      infection after allogeneic bone marrow transplantation.
AB  - Intravenous immunoglobulin is approved for use in allogeneic bone marrow
      transplant recipients for prevention of graft-versus-host disease (GVHD) and
      infections, but the minimally effective dose has not been established. In this
      multicenter, randomized, double-blind trial, patients undergoing allogeneic
      marrow transplantation were randomized to receive 100 mg/kg, 250 mg/kg, or 500
      mg/kg doses of intravenous immunoglobulin. Each dose was given weekly for 90 days
      and then monthly until 1 year after transplant. Six hundred and eighteen patients
      were evaluated. Acute GVHD (grades 2-4) occurred in 39% of the patients (80 of
      206) in the 100 mg/kg group, 42% of the patients (88 of 208) in the 250 mg/kg
      group, and in 35% of the patients (72 of 204) in the 500 mg/kg group (P = 0.344).
      Among patients with unrelated marrow donors, a higher dose of intravenous
      immunoglobulin (500 mg/kg) was associated with less acute GVHD (P = 0.07). The
      incidences of chronic GVHD, infection and interstitial pneumonia were similar for
      all three doses of intravenous immunoglobulin. The dose of intravenous
      immunoglobulin also had no effect on the types of infection, relapse of
      hematological malignancy or survival. Except for more frequent chills (P = 0.007)
      and headaches (P = 0.015) in patients given the 500 mg/kg or 250 mg/kg dose of
      immunoglobulin, adverse events were similar for all three doses. These results
      suggest that 100 mg/kg, 250 mg/kg, and 500 mg/kg doses of intravenous
      immunoglobulin are associated with similar incidences of GVHD and infections in
      most allogeneic marrow transplants. These results should be considered when
      designing cost-effective strategies for the use of intravenous immunoglobulin in
      allogeneic marrow transplants receiving other current regimens for prophylaxis of
      GVHD and infection.

PMID- 11509938
TI  - Increased hepatocyte growth factor in serum in acute graft-versus-host disease.
AB  - Hepatocyte growth factor (HGF) was reported to be effective in preventing acute
      graft-versus-host disease (GVHD) in a murine model. We examined serum HGF
      concentrations in 38 patients receiving allogeneic bone marrow transplants, and
      investigated the relationship of serum HGF concentrations to severity of acute
      GVHD. More HGF was present in sera from patients with than without acute GVHD.
      Serum HGF correlated significantly with grade of acute GVHD. Furthermore, serum
      HGF correlated with serum concentrations of C-reactive protein, gamma
      glutamyltranspeptidase (GTP), and aspartate aminotransferase (AST). Serum
      concentrations of HGF in transplanted patients without GVHD were consistently
      low, while those in patients with acute GVHD increased with exacerbation. We
      conclude that HGF was produced during induction of the GVH reaction, and probably
      increased as a physiological response.

PMID- 11509939
TI  - Final height of thalassemic patients who underwent bone marrow transplantation
      during childhood.
AB  - We evaluated the final height achieved by 47 patients who had bone marrow
      transplantation (BMT) for thalassemia major. Subjects were separated into two
      groups: patients who received BMT before 7 years of age and patients who received
      BMT after 7 years of age. Parental height and genetic target height (TH) were
      calculated. Our data indicated a strict correlation between age at time of
      transplant and final adult height. The patients whose age at transplant was <7
      years had a less impaired growth rate than did patients who were >7 years.
      Moreover, greatest loss in height was observed in subjects who had higher serum
      levels of transaminase and ferritin and these biochemical parameters were
      strictly correlated to the final adult height. Mean final adult height, however,
      did not differ from the genetic target height in subjects who received BMT before
      7 years of age and the final height SDS corrected for TH surpasses even the TH.
      In contrast, the subjects who received BMT after 7 years of age, failed to
      achieve their full genetic potential. In conclusion, short stature is present in
      a significant percentage of transplanted thalassemic children. The data in this
      study indicate a close effect of the age at time of transplant on subsequent
      growth rate, but the growth impairment in these subjects remain multifactorial.

PMID- 11509940
TI  - Progenitor and lymphoma cells in blood stem cell harvests: impact on survival
      following transplantation.
AB  - This study evaluated whether cytokine-induced blood stem cell mobilization also
      mobilized lymphoma cells and whether lymphoma cell mobilization affected outcome
      post autologous blood stem cell transplant. Blood stem cell collections from 26
      non-Hodgkin's lymphoma (NHL) patients harvested during steady-state (non
      mobilized) and from 35 NHL patients harvested after cytokine administration
      (mobilized) were studied. The harvests were cultured and molecularly evaluated
      for clonal markers of the primary lymphoma. All patients underwent high-dose
      chemotherapy and autologous transplantation. Graft products from mobilized
      patients were more likely to contain lymphoma than graft products from non
      mobilized patients (37% vs 19%) but this difference was not significant (P =
      0.16). In a multivariate analysis, lymphoma contamination was not associated with
      patient age, gender, tumor grade, prior radiotherapy, duration of prior
      chemotherapy, mononuclear cell count, or the number of aphereses performed to
      obtain the product. Heavily pre-treated patients were less likely to have
      lymphoma-contaminated harvests (P = 0.064). Lymphoma contamination was positively
      associated with the number of progenitor cells collected (P = 0.047). In
      multivariate analyses, the only significant independent predictor of lymphoma
      contamination was the number of mononuclear cells collected (P = 0.031). Lymphoma
      contamination of transplanted apheresis products had no apparent impact on event
      free and overall survival.

PMID- 11509941
TI  - Evaluation of the Murex CMV DNA Hybrid Capture assay (version 2.0) for early
      diagnosis of cytomegalovirus infection in recipients of an allogeneic stem cell
      transplant.
AB  - Early diagnosis of CMV infection based on sensitive diagnostic assays has helped
      to reduce CMV-related mortality after allogeneic stem cell transplantation (SCT).
      In this study, the commercialized Murex CMV DNA Hybrid Capture assay (version
      2.0) (HCS) was prospectively compared to an in-house CMV-DNA PCR assay from whole
      blood in patients after allogeneic stem cell transplantation. Overall, a high
      concordance between HCS and PCR was documented (kappa = 0.686; n = 385). The HCS
      assay was found to be as sensitive as the PCR indicating active CMV infection at
      a median of 35 and 34 days after transplantation, respectively. None of the HCS
      negative patients developed CMV-related symptoms (negative predictive value
      100%). Declining CMV DNA load in the blood was found to be an indicator for
      effective antiviral therapy, whereas persistence of a high viral load was
      associated with fatal CMV disease. In conclusion, the Hybrid Capture CMV DNA
      assay (v 2.0) allows early diagnosis of CMV infection after allogeneic SCT and
      assessment of the efficacy of antiviral therapy.

PMID- 11509942
TI  - Gene delivery from the E3 region of replicating human adenovirus: evaluation of
      the 6.7 K/gp19 K region.
AB  - The use of genetically engineered, replication-selective viruses to treat cancer
      is being realized with viruses such as ONYX-015, a human adenovirus that
      selectively destroys p53 mutant cancer cells. To enhance further the clinical
      efficacy of ONYX-015 and viruses like it, we have developed a novel gene delivery
      system for replicating adenoviruses. This system has two unique features. First,
      it uses the endogenous adenoviral gene expression machinery (promoter, splicing,
      polyadenylation) to drive transgene expression. Second, a single region or gene
      in the multi-gene E3 transcription unit is selectively substituted for by the
      therapeutic transgene(s). Analyzing various transgene substitutions for the 6.7
      K/gp19 K region of E3, we demonstrate the following: (1) transgene expression in
      this system is predictable and mimics the substituted endogenous gene expression
      pattern, (2) expression of surrounding E3 genes can be retained, (3) the
      insertion site choice can effect both the transgene expression level and the
      viral life cycle, and, (4) expression levels from this system are superior to
      those generated from a replication-defective virus using the HCMV enhancer
      promoter and this is dependent on viral DNA replication. This unique methodology
      has broad application to the rapidly evolving field of replicating virus-based
      therapies.

PMID- 11509943
TI  - Gene delivery from the E3 region of replicating human adenovirus: evaluation of
      the ADP region.
AB  - Genetically modified replication-selective human adenoviruses are currently
      undergoing testing in the clinical setting as anticancer agents. Coupling the
      lytic function of these viruses with virus-mediated transgene delivery represents
      a powerful extension of this treatment. We have designed a unique system for gene
      delivery from the replicating virus. It takes advantage of the endogenous gene
      expression control sequences (promoter, splicing, polyadenylation signals) to
      efficiently and predictably deliver transgenes from the non-essential E3
      transcription unit while still maintaining the expression of the remaining E3
      genes in the multi-gene transcription unit. In this article, we engineered
      restriction enzyme sites into the virus genome selectively to delete the ADP gene
      and replace it with the therapeutic transgenes CD and TNFalpha. We demonstrate
      that: (1) transgene expression from this region mirrors the substituted ADP gene;
      (2) the loss of ADP in these viruses results in infected cells with extended
      viability and protein synthesis when compared with a wild-type Ad5 infected cell;
      and (3) expression of surrounding E3 genes can be maintained in such a system.
      The potential advantages of delivering transgenes from the ADP region of the
      replicating adenovirus are discussed.

PMID- 11509944
TI  - Gene delivery from the E3 region of replicating human adenovirus: evaluation of
      the E3B region.
AB  - Successful therapies for cancer need to deal with the complexity associated with
      the human tumor. Studies of tumor and viral biology have progressed to a point
      where replicating viruses are now being engineered as potential treatments for
      human cancers. The complex nature of human cancers dictates that successful
      treatments will require combination therapies. To this end, we have focused on
      developing the gene delivery capacity of the replicating adenovirus, using the
      non-essential E3 region transcription unit as a target site for therapeutic
      transgene insertions. Utilizing the endogenous expression machinery of the E3
      region (promoter, splicing, polyA) we show that a therapeutic transgene, TNF, is
      efficiently expressed from the E3B region and with exclusive late gene expression
      kinetics. Potential clinical applications are discussed.

PMID- 11509945
TI  - Transfer of bcl-xs plasmid is effective in preventing and inhibiting rat
      hepatocellular carcinoma induced by N-nitrosomorpholine.
AB  - To examine the effect of the bcl-xs gene on the sequence from hepatic
      precancerous lesions, foci and neoplastic nodules, to hepatocellular carcinomas,
      Sprague-Dawley rats were given water containing 175 mg/l N-nitrosomorpholine
      (NNM) for 8 weeks. At weeks 1, 4 and 7, the left lobe of the rat liver was
      exposed and injected with the bcl-xs plasmid (pCR3.1-rat bcl-xs cDNA) or pCR3.1
      encapsulated in cationic empty liposomes each at a dose of 80 microg plasmid/kg
      body weight. One minute later, low-field-strength, long-duration electric pulses
      were applied to the left lobe using a pincette electrode with circular poles 1 cm
      in diameter. The in vivo electroporation procedure significantly increased the
      transfer of the reporter gene chloramphenicol acetyl transferase (CAT) plasmid
      via empty liposomes. Thus, CAT mRNA was expressed not only at the sites of
      electrode contact but at sites 0.5-1.0 cm away from the electrode, and expression
      also increased with increasing doses of plasmid, meaning that in vivo
      electroporation enabled the expression of plasmid DNA throughout an extensive
      area of the rat liver. By week 11, the neoplastic nodules were significantly
      fewer and smaller in the bcl-xs group than in the pCR3.1 group at the two sites,
      one with and the other without electrode contact. No hepatocellular carcinomas
      were found in the rats that had received the bcl-xs plasmid, whereas these tumors
      were observed in 30% of the rats given pCR3.1. Moreover, overexpression of the
      bcl-xs protein was detected, and apoptotic activity was significantly increased
      in the neoplastic nodules, foci and hepatocytes adjacent to the hepatic lesions.
      These results indicate that the bcl-xs plasmid inhibits the occurrence and growth
      of rat hepatocellular carcinoma and may thus be effective for the prevention and
      treatment of human liver tumors.

PMID- 11509946
TI  - Cytokine gene therapy of gliomas: effective induction of therapeutic immunity to
      intracranial tumors by peripheral immunization with interleukin-4 transduced
      glioma cells.
AB  - To provide a means for comparing strategies for cytokine gene therapy against
      intracranial (i.c.) tumors, we generated rat gliosarcoma 9L cells transfected
      with interleukin-4 (9L-IL4), interleukin-12 (9L-IL12), granulocyte-macrophage
      colony-stimulating factor (9L-GMCSF) or interferon-alpha (9L-IFNalpha). To
      simulate direct and highly efficient cytokine gene delivery, cytokine transfected
      9L tumors were implanted i.c. into syngeneic rats. i.c. injection led to tumor
      outgrowth in the brain and killed most animals, whereas these cell lines were
      rejected following intradermal (i.d.) injection. Cytokine-expressing i.c. 9L
      tumors, however, had a greater degree of infiltration by immune cells compared
      with control, mock-transfected 9L-neo, but to a lesser degree than i.d. cytokine
      expressing tumors. Tumor angiogenesis was suppressed in cytokine-transfected
      tumors. In a prophylaxis model, i.d. vaccination with 9L-IL4 resulted in long
      term survival of 90% of rats challenged i.c. with parental 9L; whereas 40% of 9L
      GM-CSF, 40% of 9L-IFNalpha and 0% of 9L-IL12-immunized rats were protected. In a
      therapy model (day 3 i.c. 9L tumors), only i.d. immunization with 9L-IL4 had long
      term therapeutic benefits as 43% of rats survived >100 days. These data indicate
      that peripheral immunization with 9L-IL4 had the most potent therapeutic benefit
      among various cytokines and approaches tested against established, i.c. 9L
      tumors.

PMID- 11509947
TI  - Gene therapy for preventing neuronal death using hepatocyte growth factor: in
      vivo gene transfer of HGF to subarachnoid space prevents delayed neuronal death
      in gerbil hippocampal CA1 neurons.
AB  - To develop a novel strategy to prevent delayed neuronal death (DND) following
      transient occlusion of arteries, the gene of hepatocyte growth factor (HGF), a
      novel neurotrophic factor, was transfected into the subarachnoid space of gerbils
      after transient forebrain ischemia. Importantly, transfection of HGF gene into
      the subarachnoid space prevented DND, accompanied by a significant increase in
      HGF in the cerebrospinal fluid. Prevention of DND by HGF is due to the inhibition
      of apoptosis through the blockade of bax translocation from the cytoplasm to the
      nucleus. HGF gene transfer into the subarachnoid space may provide a new
      therapeutic strategy for cerebrovascular disease.

PMID- 11509948
TI  - Successful and optimized in vivo gene transfer to rabbit carotid artery mediated
      by electronic pulse.
AB  - Several gene transfer methods, including viral or nonviral vehicles have been
      developed, however, efficacy, safety or handling continue to present problems. We
      developed a nonviral and plasmid-based method for arterial gene transfer by in
      vivo electronic pulse, using a newly designed T-shaped electrode. Using rabbit
      carotid arteries, we first optimized gene transfer efficiency, and firefly
      luciferase gene transfer via electronic pulse under 20 voltage (the pulse length:
      P(on)time 20 ms, the pulse interval: P(off) time 80 ms, number of pulse: 10
      times) showed the highest gene expression. Exogenous gene expression was
      detectable for at least up to 14 days. Electroporation-mediated gene transfer of
      E. coli lacZ with nuclear localizing signal revealed successful gene transfer to
      luminal endothelial cells and to medial cells. Histological damage was recognized
      as the voltage was increased but neointima formation 4 weeks after gene transfer
      was not induced. In vivo electroporation-mediated arterial gene transfer is
      readily facilitated, is safe and may prove to be an alternative form of gene
      transfer to the vasculature.

PMID- 11509949
TI  - Effect of immunity on gene delivery into anterior horn motor neurons by live
      attenuated herpes simplex virus vector.
AB  - Efficient and prolonged foreign gene expression has been demonstrated in the
      bilateral anterior horn motor neurons of the spinal cord by intramuscular
      inoculation with attenuated herpes simplex virus (HSV) expressing latency
      associated transcript promoter-driven beta-galactosidase (betaH1). To examine the
      effect of immunity on the gene delivery, betaH1 was applied in rats immunized
      subcutaneously or intramuscularly with the parent HF strain. Rats were immunized
      subcutaneously with HF strain and 28 days later when the high antibody titer was
      maintained, betaH1 was inoculated into the right gastrocnemius muscle. Second, 35
      days after inoculation with HF strain into the right gastrocnemius muscle, betaH1
      was inoculated at the same site. In both ways of immunization, immunity did not
      abolish or prevent the transgene expression in the anterior horn motor neurons,
      but attenuated the range and the number of the beta-galactosidase-positive
      neurons from about 85% to 50-65% on 28 days after inoculation with betaH1.
      However, beta-galactosidase activity was observed in a wide range of the
      bilateral anterior horn motor neurons without significant pathological changes.
      These findings support the feasibility of the attenuated HSV vector in gene
      delivery into the central nervous system, even in the presence of immunity.

PMID- 11509950
TI  - On the mechanism whereby cationic lipids promote intracellular delivery of
      polynucleic acids.
AB  - The mechanism whereby cationic lipids destabilize cell membranes to facilitate
      the intracellular delivery of macromolecules such as plasmid DNA or antisense
      oligonucleotides is not well understood. Here, we show that cationic lipids can
      destabilize lipid bilayers by promoting the formation of nonbilayer lipid
      structures. In particular, we show that mixtures of cationic lipids and anionic
      phospholipids preferentially adopt the inverted hexagonal (H(II)) phase. Further,
      the presence of 'helper' lipids such as dioleoylphosphatidylethanolamine or
      cholesterol, lipids that enhance cationic lipid-mediated transfection of cells
      also facilitate the formation of the H(II)phase. It is suggested that the ability
      of cationic lipids to promote nonbilayer structures in combination with anionic
      phospholipids leads to disruption of the endosomal membrane following uptake of
      nucleic acid-cationic lipid complexes into cells, thus facilitating cytoplasmic
      release of the plasmid or oligonucleotide.

PMID- 11509951
TI  - Radio-responsive recA promoter significantly increases TNFalpha production in
      recombinant clostridia after 2 Gy irradiation.
AB  - One of the major problems with gene therapy today is the lack of tumour
      specificity. The use of anaerobic apathogenic clostridia as a gene transfer
      system can target anoxic areas within the tumour. These bacteria can be
      genetically modified to express therapeutic proteins such as TNFalpha locally in
      the tumour. As shown in our results, ionising irradiation can be used in
      clostridia to activate genes encoding cytotoxic agents under control of a
      radiation-inducible promoter. A 44% significant increase (P < 0.05) in TNFalpha
      secretion was seen 3.5 h after a single dose of 2 Gy. A second dose of 2 Gy was
      also capable of repeating gene activation and gave a significant increase of
      TNFalpha production of 42% (P < 0.05). These results provide evidence that
      spatial and temporal control of gene expression can be achieved using a radio
      inducible promoter. Repetitive gene activation was feasible with a second dose of
      2 Gy, indicating that fractionated radiotherapy could lead to repeated gene
      induction resulting in prolonged and enhanced protein expression. Gene targeting
      by ionising radiation could thus provide a new means of increasing the
      therapeutic ratio in cancer treatment.

PMID- 11509952
TI  - Targeted gene transfer to lymphocytes using murine leukaemia virus vectors
      pseudotyped with spleen necrosis virus envelope proteins.
AB  - In contrast to murine leukaemia virus (MLV)-derived vector systems, vector
      particles derived from the avian spleen necrosis virus (SNV) have been
      successfully targeted to subsets of human cells by envelope modification with
      antibody fragments (scFv). However, an in vivo application of the SNV vector
      system in gene transfer protocols is hampered by its lack of resistance against
      human complement. To overcome this limitation we established pseudotyping of MLV
      vector particles produced in human packaging cell lines with the SNV envelope
      (Env) protein. Three variants of SNV Env proteins differing in the length of
      their cytoplasmic domains were all efficiently incorporated into MLV core
      particles. These pseudotype particles infected the SNV permissive cell line D17
      at titers of up to 10(5) IU/ml. A stable packaging cell line (MS4) of human
      origin released MLV(SNV) pseudotype vectors that were resistant against human
      complement inactivation. To redirect their tropism to human T cells, MS4 cells
      were transfected with the expression gene encoding the scFv 7A5 in fusion with
      the transmembrane domain (TM) of the SNV Env protein, previously shown to
      retarget SNV vector particles to human lymphocytes. MLV(SNV-7A5)-vector particles
      released from these cells were selectively infectious for human T cell lines. The
      data provide a proof of principle for targeting MLV-derived vectors to
      subpopulations of human cells through pseudotyping with SNV targeting envelopes.

PMID- 11509953
TI  - Fibroblast growth factor-II gene therapy reverts the clinical course and the
      pathological signs of chronic experimental autoimmune encephalomyelitis in
      C57BL/6 mice.
AB  - The development of therapies aimed to promote remyelination is a major issue in
      chronic inflammatory demyelinating disorders of the central nervous system (CNS)
      such as multiple sclerosis (MS), where the permanent neurological impairment is
      due to the axonal loss resulting from recurrent episodes of immune-mediated
      demyelination. Here, we show that the intrathecal injection of a herpes simplex
      virus (HSV) type-1 replication-defective multigene vector, engineered with the
      human fibroblast growth factor (FGF)-II gene (TH:bFGF vector), was able to
      significantly revert in C57BL/6 mice the clinicopathological signs of chronic
      experimental autoimmune encephalomyelitis (EAE), the animal model of MS. The
      treatment with the TH:bFGF vector was initiated within 1 week after the clinical
      onset of EAE and was effective throughout the whole follow-up period (ie 60
      days). The disease-ameliorating effect in FGF-II-treated mice was associated
      with: (1) CNS production of FGF-II from vector-infected cells which were
      exclusively located around the CSF space (ependymal, choroidal and leptomeningeal
      cells); (2) significant decrease (P < 0.01) of the number of myelinotoxic cells
      (T cells and macrophages) both in the CNS parenchyma and in the leptomeningeal
      space; and (3) significant increase (P < 0.01) of the number of oligodendrocyte
      precursors and of myelin-forming oligodendrocytes in areas of demyelination and
      axonal loss. Our results indicate that CNS gene therapy using HSV-1-derived
      vector coding for neurotrophic factors (ie FGF-II) is a safe and non-toxic
      approach that might represent a potential useful 'alternative' tool for the
      future treatment of immune-mediated demyelinating diseases.

PMID- 11509954
TI  - Rat marrow stromal cells rapidly transduced with a self-inactivating retrovirus
      synthesize L-DOPA in vitro.
AB  - Autologous bone marrow stromal cells engineered to produce 3,4,
      dihydroxyphenylalanine (L-DOPA) can potentially be used as donor cells for neural
      transplantation in Parkinson's disease. Here, we examined the possibility of
      using several different promoters and either a self-inactivating retrovirus
      (pSIR) or standard retroviruses to introduce into marrow stromal cells (MSCs),
      the two genes necessary for the cells to synthesize L-DOPA. pSIR vectors were
      constructed using the mouse phosphoglycerate kinase-1 (PGK) promoter or the
      cytomegalovirus (CMV) promoter to drive expression of either a GFP reporter gene
      or a bicistronic sequence containing the genes for human tyrosine hydroxylase
      type I (TH) and rat GTP cyclohydrolase I (GC) separated by an internal ribosome
      entry site (IRES). rMSCs were successfully transduced with both standard
      retroviral vectors and pSIR containing the PGK promoter. Transduced rMSCs
      expressed GFP (90.4--94.4% of cells) or were able to synthesize and secrete L
      DOPA (89.0--283 pmols/10(6) cells/h). After transduced rMSCs were plated at low
      density (3--6 cells/cm(2)), the cells expanded over 1000-fold in 3--4 weeks, and
      the rMSCs continued to either express GFP or produce L-DOPA. Furthermore, two
      high-expressing clones were isolated and expanded at low-density from rMSCs
      transduced with pSIR driven by the PGK promoter (97.0% GFP+ or 1096.0 pmols L
      DOPA/10(6) cells/h).

PMID- 11509955
TI  - Human myeloid dendritic cells transduced with an adenoviral interleukin-10 gene
      construct inhibit human skin graft rejection in humanized NOD-scid chimeric mice.
AB  - Human myeloid DC were generated from peripheral blood mononuclear cells by
      monocyte adhesion and subsequent culture with rhGM-CSF and rhIL-4. We transduced
      immature (day 5 of culture) myeloid DC with an E1-deleted replication-deficient
      adenoviral vector encoding the cytokine IL-10 (AdV IL-10) and a control
      adenovirus MX-17 (AdV MX 17). Human DC transduced with AdV IL-10 showed
      inhibition of the mixed leukocyte culture, reduced cell surface expression of co
      stimulatory molecules (CD80/CD86) and were unable to produce the potent allo
      stimulatory cytokine, interleukin-12. In order to test the in vivo properties of
      these cells a humanized immunodeficient mouse skin transplantation model was
      developed. Immunodeficient NOD-scid mice were engrafted with human skin,
      reconstituted via intraperitoneal injection with allogeneic mononuclear cells
      (MNC) mixed with 1 x 10(6) DC that were autologous to the skin donor and that had
      been transduced with either AdV IL-10 or AdV MX-17. Skin grafts were removed at
      day 7 and 14 after reconstitution and studied histologically for evidence of
      rejection. In animals that received DC modified with AdV IL-10 there was reduced
      skin graft rejection as characterized by reduced mononuclear cell infiltration
      and less dermo-epidermal junction destruction compared with those animals that
      received DC modified with the control virus alone. Injection of equivalent
      numbers of donor-derived fibroblasts transduced with AdV IL-10 were ineffective
      at modifying rejection of skin grafts. Immunosuppressive cytokine gene therapy
      targeting human DC is a novel means of inhibition of the alloimmune response.

PMID- 11509956
TI  - In vivo electroporation-mediated transfer of interleukin-12 and interleukin-18
      genes induces significant antitumor effects against melanoma in mice.
AB  - Direct intratumoral transfection of cytokine genes was performed by means of the
      in vivo electroporation as a novel therapeutic strategy for cancer. Plasmid
      vectors carrying the firefly luciferase, interleukin (IL)-12 and IL-18 genes were
      injected into established subcutaneous B16-derived melanomas followed by electric
      pulsation. When plasmid vectors with Epstein--Barr virus (EBV) nuclear antigen 1
      (EBNA1) gene were employed, the expression levels of the transgenes were
      significantly higher in comparison with those obtained with conventional plasmid
      vectors. In consequence of the transfection with IL-12 and IL-18 genes, serum
      concentrations of the cytokines were significantly elevated, while interferon
      (IFN)-gamma also increased in the sera of the animals. The IL-12 gene
      transfection resulted in significant suppression of tumor growth, while the
      therapeutic effect was further improved by co-transfection with IL-12 and IL-18
      genes. Repetitive co-transfection with IL-12 and IL-18 genes resulted in
      significant prolongation of survival of the animals. Natural killer (NK) and
      cytotoxic T lymphocyte (CTL) activities were markedly enhanced in the mice
      transfected with the cytokine genes. The present data suggest that the cytokine
      gene transfer can be successfully achieved by in vivo electroporation, leading to
      both specific and nonspecific antitumoral immune responses and significant
      therapeutic outcome.

PMID- 11509957
TI  - Hepatic intra-arterial delivery of a retroviral vector expressing the cytosine
      deaminase gene, controlled by the CEA promoter and intraperitoneal treatment with
      5-fluorocytosine suppresses growth of colorectal liver metastases.
AB  - Targeting of colorectal liver metastases by regional gene therapy was tested in a
      clinically relevant syngeneic model. First, the CEA-CD-113 retroviral vector
      containing the cytosine deaminase gene controlled by the CEA specific tumour cell
      promoter, was shown in vitro to convert 5-fluorocytosine to 5-fluorouracil,
      resulting in cancer cell killing with a large bystander effect. Second, 10 days
      after the establishment of liver metastases, retroviral vectors were delivered to
      the liver by hepatic artery injection. After 5-fluorocytosine administration for
      7 days, most surface metastases disappeared and tumour volumes were suppressed up
      to 8.2-fold. The results support the development of this approach for patient
      treatment.

PMID- 11509958
TI  - Self-complementary recombinant adeno-associated virus (scAAV) vectors promote
      efficient transduction independently of DNA synthesis.
AB  - Adeno-associated virus (AAV) vectors package single-stranded genomes and require
      host-cell synthesis of the complementary strand for transduction. However, when
      the genome is half wild-type size, AAV can package either two copies, or dimeric
      inverted repeat DNA molecules. Dimeric, or self-complementary molecules (scAAV)
      should spontaneously reanneal, alleviating the requirement for host-cell DNA
      synthesis. We generated and characterized scAAV vectors in order to bypass the
      rate-limiting step of second-strand synthesis. In vitro, scAAV vectors were five-
      to 140-fold more efficient transducing agents than conventional rAAV, with a
      5.9:1 particle to transducing unit ratio. This efficiency is neither greatly
      increased by co-infection with Ad, nor inhibited by hydroxyurea, demonstrating
      that transduction is independent of DNA synthesis. In vivo, scAAV expressing
      erythropoietin resulted in rapid and higher levels of hematocrit than a
      conventional single-stranded vector. These novel scAAV vectors represent a
      biochemical intermediate in rAAV transduction and should provide new insights
      into the biology of vector transduction.

PMID- 11509959
TI  - Adenovirus-transduced dendritic cells stimulate cellular immunity to melanoma via
      a CD4(+) T cell-dependent mechanism.
AB  - We previously showed that genetic immunization of C57BL/6 mice with recombinant
      adenovirus encoding human TRP2 (Ad-hTRP2) was able to circumvent tolerance and
      induce cellular and humoral immune responses to murine TRP2 associated with
      protection against metastatic growth of B16 melanoma. In the present study we
      compared delivery of Ad-hTRP2 with cultured dendritic cells (DC) and direct
      injections of Ad-hTRP2. We show that application of Ad-hTRP2 with cultured DC
      enhanced protective immunity to B16 melanoma cells. Most importantly, delivery of
      recombinant adenovirus with DC alters the character of the immune response
      resulting in preferential stimulation of strong cellular immunity in the absence
      of significant humoral immunity to the encoded antigen. Adoptive transfer of
      lymphocytes from mice immunized with Ad-hTRP2-transduced DC confirmed that
      cellular components of the immune response were responsible for rejection of B16
      melanoma. The protective efficacy of Ad-hTRP2-transduced DC clearly depended on
      the presence of CD4(+) T helper cells. Furthermore, AD-hTRP2-transduced DC, but
      not direct injection of Ad-hTRP2, were effective in the presence of neutralizing
      anti-adenoviral antibodies. These preclinical studies demonstrate the superiority
      of melanoma vaccines consisting of cultured DC transduced with recombinant
      adenoviruses encoding melanoma antigens.

PMID- 11509960
TI  - Optimisation of electrotransfer of plasmid into skeletal muscle by pretreatment
      with hyaluronidase -- increased expression with reduced muscle damage.
AB  - The efficiency of plasmid gene transfer to skeletal muscle can be significantly
      improved by the application of an electrical field to the muscle following
      injection of plasmid DNA. However, this electrotransfer is associated with
      significant muscle damage which may result in substantial loss of transfected
      muscle fibres. Reduction of the voltage used in the technique can result in a
      decrease in muscle damage, with a concomitant reduction in expression, but
      without a significant decrease in the number of transfected fibres. Pre-treatment
      of the muscle with a solution of bovine hyaluronidase greatly increases the
      efficiency of plasmid gene transfer when used in conjunction with
      electrotransfer, but not when used alone. This combination treatment results in
      greatly enhanced levels of transfected muscle fibres without the increases in
      muscle damage associated with the electrotransfer process.

PMID- 11509961
TI  - A novel system for mitigation of ectopic transgene expression induced by
      adenoviral vectors.
AB  - Adenoviral (Ad) vectors are good candidates for gene therapy in view of their
      high in vivo gene delivery efficiency. However, greater control over the tissue
      distribution of transgene expression is required to avoid potentially deleterious
      effects in non-target organs. In this regard, the liver is particularly at risk
      due to the high natural tropism of Ad for this organ, where dose limiting
      toxicity has been seen due to toxic transgene expression. We hypothesized that
      the cre/loxP system could be utilized to reduce unintended transgene expression
      at this site. This concept was tested using an Ad vector (AdLCLLL) carrying a
      reporter gene cassette in which the promoter and luciferase gene were flanked by
      LoxP sequences. Co-administration of this vector with a second vector carrying
      the cre recombinase gene in vitro and in vivo resulted in specific down
      regulation of transgene expression. This novel approach thus has the potential to
      improve the safety of gene therapy strategies that rely upon the delivery of
      genes which may be hepatotoxic.

PMID- 11509962
TI  - Liver-targeted gene transfer into a human hepatoblastoma cell line and in vivo by
      sterylglucoside-containing cationic liposomes.
AB  - We investigated the transfection efficiency of beta-sitosterol beta-D-glucoside
      (Sit-G)-containing liposome/DNA complex (Sit-G-liposome/DNA complex) for liver
      targeting. The Sit-G-liposome/DNA complex was composed of Tfx-20 reagent (Tfx),
      ie synthetic cationic lipid [N,N,N',N'-tetramethyl-N,N'-bis(2-hydroxyethyl)-2,3
      di(oleoyloxy)-1,4-butanediammonium iodide] with L
      dioleoylphosphatidylethanolamine (DOPE), 3 beta[N-(N',N'-dimethylaminoethane)
      carbamoyl]cholesterol (DC-Chol) and Sit-G with plasmid DNA. The in vitro studies
      were performed in HepG2 cells in serum-containing medium and the in vivo studies
      were carried out in the mice following intravenous injection. The Sit-G-liposome
      produced a Sit-G-liposome/DNA complex of relatively small size (100--250 nm).
      Transfection efficiency of the luciferase marker gene by Sit-G-liposome/DNA
      complex was increased in the presence of 10% serum in vitro, and was selectively
      high in the mouse liver reaching expression values up to an average of 14.9 pg
      luciferase/mg tissue protein, compared with Tfx/DNA complex, which showed
      approximately three-fold higher gene expression than Sit-G-liposome/DNA complex
      in vitro. High in vitro transfection efficiency by Sit-G-liposome/DNA complex
      seemed to be possible even with large lipid precipitates, whereas high in vivo
      activity seemed to be related to small and dispersed complexes. The interaction
      of liposome/DNA complexes with serum may be a key point to predict the in vivo
      efficiency of a liposome vector.

PMID- 11509966
TI  - Extracts from fruits of saw palmetto (Sabal serrulata) and roots of stinging
      nettle (Urtica dioica): viable alternatives in the medical treatment of benign
      prostatic hyperplasia and associated lower urinary tracts symptoms.
AB  - Benign prostatic hyperplasia (BPH) and associated lower urinary tract symptoms
      (LUTS) are very common disorders in aging men. Despite the great clinical
      importance, many aspects of their aetiology remain uncertain although it is
      generally accepted that advanced age and testicular androgens are important
      requirements for the development of these complaints. The currently available
      therapeutic options include watchful waiting, changes of life style, medical
      treatments and invasive therapies. In many European countries the use of
      phytopharmaceuticals for the management of BPH and related LUTS is common and
      these products represent up to 80 % of all drugs prescribed for this disorder. In
      particularly, extracts from the fruits of saw palmetto (Sabal serrulata, syn.
      Serenoa repens) and the roots of stinging nettle (Urtica dioica) are popular.
      During the last years numerous papers have been published which elaborated on the
      pharmacological activities and the clinical assessment of these herbal remedies.
      These investigations have not only broadened the scientific basis for the
      rational use of phytotherapeutics but have also provided evidence for their
      therapeutic efficacy and favourable safety profile.

PMID- 11509967
TI  - Inhibitory activity for chitin synthase II from Saccharomyces cerevisiae by
      tannins and related compounds.
AB  - In the course of search for potent inhibitors of chitin synthase II from natural
      resources, seven tannins and related compounds were isolated from the aerial part
      of Euphorbia pekinensis and identified as gallic acid (1), methyl gallate (2), 3
      O-galloyl-(-)-shikimic acid (3), corilagin (4), geraniin (5), quercetin-3-O-(2"-O
      galloyl)-beta-D-glucoside (6), and kaempferol-3-O-(2"-O-galloyl)-beta-D-glucoside
      (7). These and nine related compounds, (-)-quinic acid (8), (-)-shikimic acid
      (9), ellagic acid (10), kaempferol (11), quercetin (12), quercitrin (13), rutin
      (14), quercetin-3-O-(2"-O-galloyl)-beta-D-rutinoside (15) and 1,3,4,6-tetra-O
      galloyl-beta-D-glucose (16), were evaluated for the inhibitory activity against
      chitin synthase II and III. They inhibited chitin synthase II with IC(50) values
      of 18-206 microM, except for two organic acids, (-)-quinic acid (8) and (-)
      shikimic acid (9). Among them, 3-O-galloyl-(-)-shikimic acid (3) was the most
      potent inhibitor against chitin synthase II of Saccharomyces cerevisiae with an
      IC(50) value of 18 microM. The inhibition appears to be selective for chitin
      synthase II, as they did not appreciably inhibit chitin synthase III.

PMID- 11509968
TI  - Rutaecarpine, a quinazolinocarboline alkaloid, inhibits prostaglandin production
      in RAW264.7 macrophages.
AB  - In order to delineate the mechanism involved in the anti-inflammatory activity of
      rutaecarpine, its effects on the production of prostaglandin (PG) and therein
      involved enzymes were examined. Rutaecarpine reduced the production of PGE(2) in
      RAW264.7 cells treated with lipopolysaccharide (LPS) in a dose dependent manner
      when added to the culture media at the time of stimulation. However, the
      inhibition of total cellular cyclooxygenase (COX) activity under the same
      experimental condition was observed only at high concentrations of rutaecarpine.
      Rutaecarpine did not affected the levels of COX-2 mRNA and protein in macrophages
      stimulated with LPS. Calcium ionophore A23187 induced-PG production and [(3)H]
      arachidonic acid release were significantly decreased by the pretreatment of
      rutaecarpine for 30 minutes. With the same treatment schedule, however,
      rutaecarpine failed to alter the activities of cellular COX-1 and COX-2.
      Collectively, our data suggest that anti-inflammatory effect of rutaecarpine is,
      at least in part, ascribed to the diminution of PG production through inhibition
      of arachidonic acid release albeit the nature of its effects on PLA(2) activity
      remains to be elaborated.

PMID- 11509969
TI  - Molecular identification of potential selective estrogen receptor modulator
      (SERM) like properties of phytoestrogens in the human breast cancer cell line MCF
      7.
AB  - Numerous epidemiologic studies revealed that ethnic populations with higher
      dietary intake of phytoestrogens have the lowest incidence for breast cancer. The
      molecular mechanisms which may be responsible for this cancer protective action
      of phytoestrogens are so far only barely characterised. There are some hints that
      phytoestrogens may act like selective estrogen receptor modulators (SERMs) on the
      breast. For this reason we have investigated potential SERM-like properties of
      the phytoestrogens daidzein (Dai), coumestrol (Cou), and genistein (Gen) in the
      human breast cancer cell line MCF-7. Effects of these substances on progesterone
      (PR) and estrogen receptor alpha (ER) mRNA expression and estrogen receptor alpha
      protein levels were studied in comparison to estradiol (E2) and the synthetic
      SERMs raloxifene (Ral) and faslodex (ICI 182 780). PR mRNA expression was up
      regulated after administration of Cou, whereas treatment with Dai and Gen induced
      only a faint increase. ER mRNA expression was down-regulated by Cou but not
      affected by Dai and Gen. The content of ER protein in the breast cancer cells was
      strongly decreased by Gen, only a faint reduction could be observed following
      administration of Cou, whereas administration of Dai slightly increases ER
      protein levels. In summary and in comparison to the effects observed after
      administration of E2, Ral, and ICI it turned out that Cou shows molecular
      properties which are very similar to an estrogen receptor agonist like E2,
      whereas the molecular properties of Gen are comparable to the SERMs ICI and Ral.
      These results clearly indicate that phytoestrogens differ significantly in regard
      to their molecular action on breast cancer cells and can be subdivided into
      distinct functional categories.

PMID- 11509970
TI  - Cytotoxicity and lipid peroxidation-inhibiting activity of flavonoids.
AB  - Thirty-five flavonoids of seven different types, namely isoflavonoids, chalcones,
      dihydroflavonols, flavanols, flavanones, flavones, and flavonols were
      investigated for their ability to inhibit ascorbate-induced microsomal lipid
      peroxidation and their cytotoxicity. For each activity a structure-activity
      relationship was established. Subsequently, an antioxidant selectivity index, i.
      e., the maximal non-toxic dose divided by the IC(50) value for lipid
      peroxidation, was introduced. Kaempferol showed the highest antioxidant
      selectivity index of all flavonoids tested.

PMID- 11509971
TI  - Purification of phenylethanoids from Brandisia hancei and the antiproliferative
      effects on aortic smooth muscle.
AB  - The present study describes the isolation and purification of acteoside, 2'
      acetylacteoside, poliumoside and brandioside, four phenylethanoid glycosides from
      Brandisia hancei. We examined their effects on the proliferation of cultured A7r5
      rat aortic smooth muscle cells. The proliferative response was measured from the
      [(3)H]-thymidine incorporation into DNA. All four glycosides suppressed the
      proliferative response in the presence of 2 % or 5 % fetal bovine serum in a
      concentration-dependent manner. The rank order of effectiveness for inhibition of
      cell proliferation was: brandioside > or = poliumoside > 2'-acetylacteoside > or
      = acteoside. The acetyl group at position 2' of glucose does not seem necessary
      for the anti-proliferative effects of acteoside and 2'-acetylacteoside, while the
      hydroxy groups of the aromatic rings appear to play a role. Inhibition of smooth
      muscle cell proliferation by phenylethanoids indicates that these compounds may
      have preventative effects on arteriosclerosis.

PMID- 11509972
TI  - Reversal of chloroquine and mefloquine resistance in Plasmodium falciparum by the
      two monoindole alkaloids, icajine and isoretuline.
AB  - Eight naturally occurring monoindole alkaloids were evaluated in vitro for their
      ability to inhibit Plasmodium falciparum growth and, in drug combination, to
      reverse the resistance of a chloroquine-resistant strain of Plasmodium
      falciparum. None of these indole alkaloids has significant intrinsic
      antiplasmodial activity (IC(50) > 10 microM or 5 microg/ml). Nevertheless, three
      alkaloids (icajine, isoretuline and strychnobrasiline) did reverse chloroquine
      resistance at concentrations between 2.5 and 25 microg/ml (IF of 12.82 for
      isoretuline on W2 strain). The Interaction Factor (IF) equals 2, < 2, or > 2 for
      additive, antagonistic or synergistic effects of alkaloids on chloroquine
      inhibition, respectively. Icajine and isoretuline were also assessed in vitro for
      their mefloquine potentiating activity on a mefloquine-resistant strain of
      Plasmodium falciparum. Only icajine proved to be synergistic with mefloquine (IF
      = 15.38).

PMID- 11509973
TI  - Antiviral, haemolytic and molluscicidal activities of triterpenoid saponins from
      Maesa lanceolata: establishment of structure-activity relationships.
AB  - Ten saponins isolated from the leaves of Maesa lanceolata were tested for their
      antiviral, haemolytic and molluscicidal activities. The influence of the
      substitution pattern of these acylated triterpenoid saponins on their biological
      activities was investigated and structure-activity relationships were
      established. Maesasaponin VI(2) (3 beta-O-[[alpha-L-rhamnopyranosyl-(1 --> 2)
      beta-D-galactopyranosyl-(1 --> 3)]-[beta-D-galactopyranosyl-(1 --> 2)]-beta-D
      glucopyranuronyl]-21 beta,22 alpha-diangeloyloxy-13 beta,28-epoxyolean-16
      alpha,28 alpha-diol), the most potent molluscicidal compound (LC(50) 0.5 ppm),
      also showed virucidal and haemolytic activity. In general, 21,22-diacylation
      appeared to be associated with a virucidal (reduction factor of the viral titer >
      or = 10(3) at 50 microg/ml) and haemolytic activity (HC(50) < or = 1 microg/ml).

PMID- 11509974
TI  - Neurotrophic and neuroprotective actions of ginsenosides Rb(1) and Rg(1).
AB  - The ginsenosides have many pharmacological actions, including various actions on
      the nervous system. Our previous studies have demonstrated that two ginsenosides,
      Rb(1) and Rg(1) improve performance in a passive avoidance-learning paradigm and
      enhance cholinergic metabolism. The present study was designed to examine the
      cellular neurotrophic and neuroprotective actions of two pure ginsenosides in two
      model systems. PC12 cells were grown in the absence or presence of nerve growth
      factor (NGF) as a positive control, and different concentrations of Rb(1) or
      Rg(1). To assess neurotrophic properties, neurite outgrowth was quantified for
      representative fields of cells. After 8 days in culture, both ginsenosides
      enhanced neurite outgrowth in the presence of a sub-optimal dose of (2 ng/ml)
      NGF, but did not significantly stimulate neurite outgrowth in the absence of NGF.
      However, after 18 days in culture, both ginsenosides increased neurite outgrowth
      in the absence of NGF. SN-K-SH cells were grown in the absence or presence of
      MPTP or beta-amyloid to assess neuroprotection. Rb(1) and Rg(1) both reversed
      MPTP-induced cell death. beta-Amyloid-induced cell death was not reversed by
      either ginsenoside, but Rg(1) produced a modest enhancement of cell death in this
      model. These results suggest that these two ginsenosides have neurotrophic and
      selective neuroprotective actions that may contribute to the purported
      enhancement of cognitive function.

PMID- 11509975
TI  - Effect of honey and sugars on the metabolism and disposition of naringin in
      rabbits.
AB  - To investigate the effect of honey and sugars on the metabolism and disposition
      of naringin, rabbits were administered naringin alone and naringin with honey or
      its component sugars - fructose, glucose and sucrose in crossover designs. An
      HPLC method was developed to determine naringenin in serum after enzymatic
      hydrolysis. Our results indicate that honey, fructose and sucrose significantly
      reduced AUC(0-t) of naringenin by 41 %, 61 % and 45 %, respectively. In vitro
      studies using a rabbit feces suspension to incubate naringin without or with
      honey or the respective sugars were employed to investigate the mechanism of this
      interaction. The results indicated that honey and its component sugars did not
      affect the rate and extent of naringin hydrolysis, whereas the degradation of
      naringenin was significantly enhanced in the presence of honey and fructose. It
      could be concluded that concomitant intake of honey, fructose and sucrose
      resulted in the reduction of naringin absorption which could be attributable in
      part to the enhanced preabsorption degradation of absorbable naringenin in the
      large intestine.

PMID- 11509976
TI  - Two new bislabdane-type diterpenoids and three new diterpenoids from the roots of
      Cunninghamia lanceolata.
AB  - Two new bislabdane-type diterpenoids lanceolatin (1), lancelatol (2) and three
      new diterpenoids 15-nor-14-oxo-8(17),12-labdanien-14,18-dionic acid (3),
      8(17),12,14-labdantrien-18-oic acid (4) and 8(17),12,14-labdantrien-18-ol (5),
      together with 7 known diterpenoids were isolated from the roots of Cunninghamia
      lanceolata. Their structures were determined by spectroscopic and chemical
      methods. All of these compounds were isolated from the species for the first
      time. One of the isolated compounds showed a significant inhibition effect on
      mouse hind-paw edema induced by carrageenan.

PMID- 11509977
TI  - Flavanone glycosides from Citrus junos and their anti-influenza virus activity.
AB  - By bioactivity-guided fractionation, a new flavanone triglycoside, naringenin 7-O
      (2",6"-di-O-alpha-rhamnopyranosyl)-beta-glucopyranoside (1), as well as
      hesperetin 7-O-(2", 6"-di-O-alpha-rhamnopyranosyl)-beta-glucopyranoside (2),
      hesperidin (3) and narirutin (4) have been isolated from the fruits of Citrus
      junos Tanaka (Rutaceae). In addition, hesperetin 7-O-(2",6"-di-O-alpha
      rhamnopyranosyl)-beta-glucopyranoside (2) is reported for the first time from
      this plant and inhibits the influenza A virus.

PMID- 11509978
TI  - A curcuminoid and sesquiterpenes as inhibitors of macrophage TNF-alpha release
      from Curcuma zedoaria.
AB  - Tumor necrosis factor-alpha (TNF-alpha) is one of the major mediators produced in
      activated macrophages which contribute to the circulatory failure associated with
      septic shock. In the course of screening marketed oriental anti-inflammatory
      herbal drugs for TNF-alpha antagonistic activity, a crude methanolic extract of
      the rhizomes of Curcuma zedoaria exhibited significant activity. The activity
      guided fractionation and repetitive chromatographic procedures with the EtOAc
      soluble fraction resulted in the isolation of three active compounds. They were
      identified as 1,7-bis(4-hydroxyphenyl)-1,4,6-heptatrien-3-one (1), procurcumenol
      (2) and epiprocurcumenol (3) by spectral data analysis. They inhibited the
      production of TNF-alpha by lipopolysaccharide (LPS)-activated macrophages from
      the results of bioassay (IC(50) values of 1 and 2 are 12.3 and 310.5 microM,
      respectively) and Western blot assay. These results imply that the traditional
      use of C. zedoaria rhizome as anti-inflammatory drug may be explained at least in
      part, by the inhibition of TNF-alpha production.

PMID- 11509979
TI  - Estrogenic activity of phenolic compounds from Nigella damascena evaluated using
      a recombinant yeast screen.
AB  - We used a yeast estrogen screen (YES) containing human estrogen receptor to
      evaluate the estrogenic activity of both crude extracts and simple pure phenolic
      compounds from Nigella damascena seeds. Estrogenic activity was established in
      the methanolic and aqueous extracts of the seeds as well as in two simple
      phenolic compounds isolated from the methanolic extract, 2,4
      dihydroxyphenylacetic acid, 3,4-dihydroxy-beta-phenethyl alcohol.

PMID- 11509980
TI  - Cytotoxic cyclopenta[b]benzofuran derivatives from the stem bark of Aglaia
      formosana.
AB  - A new cytotoxic cyclopenta[b]benzofuran derivative, aglaiformosanin (1) and three
      known cyclopenta[b]benzofuran derivatives (2 - 4) were isolated from the stem
      bark of Aglaia formosana. Compounds 1 - 4 exhibited potent cytotoxicity against
      the P-388, KB, HT-29, HL-60, and A549 cell lines. The structure of compound 1 was
      determined by spectroscopic analysis.

PMID- 11509981
TI  - Cytotoxic sesquiterpene lactones mediate their death-inducing effect in leukemia
      T cells by triggering apoptosis.
AB  - Cytotoxicity is a well characterized property of sesquiterpene lactones. In the
      present study, the question was addressed whether sesquiterpene lactones mediate
      their cytotoxic effect by triggering apoptosis. Four compounds, ambrosin,
      alantolactone, hymenin and helenalin were shown to induce apoptosis in Jurkat
      leukemia T cells as judged by cell morphology, the appearance of apoptotic nuclei
      as well as the translocation of phosphatidylserine to the outer surface of the
      cell membrane.

PMID- 11509982
TI  - Cytotoxic neolignans and butanolides from Machilus obovatifolia.
AB  - From the chloroform-soluble portion of the stem wood of Machilus obovatifolia,
      one new neolignan, perseal F (1), four known neolignans, perseal G (2), licarin
      A, licarin B, acuminatin, two butanolides, linderanolide E and isolinderanolide
      E, two steroids, beta-sitosterol, beta-sitosterol-beta-D-glucoside, and
      syringaldehyde were isolated. Perseal F (1) and G (2) are neolignans that have a
      C-1' formyl side chain instead of a propenyl group. Compound 2 was isolated in a
      mixture with acuminatin. The structure of 2 was identified by comparison with the
      product formed by the Lemieux-von Rudloff oxidation of licarin B. Two minor
      oxidative by-products, 2a and 2b, were also obtained. Linderanolide E showed
      cytotoxicities against P-388, KB16, A549 and HT-29, 1 against P-388, KB16 and HT
      29, and isolinderanolide E against P-388, cancer cell lines, respectively. All
      structures were identified by means of spectroscopic analyses.

PMID- 11509983
TI  - Antibacterial activity of Hydrastis canadensis extract and its major isolated
      alkaloids.
AB  - The antibacterial activity of extract and isolated major alkaloids (berberine,
      beta-hydrastine, canadine and canadaline) of Hydrastis canadensis L.
      (Ranunculaceae) was evaluated against 6 strains of microorganism: Staphylococcus
      aureus (ATCC 25 993 and ATCC 6538P), Streptococcus sanguis (ATCC 10 556),
      Escherichia coli (ATCC 25 922), Pseudomonas aeruginosa (ATCC 27 853).
      Bactericidal activity was evaluated by contact test by measuring the "killing
      time" on a low density bacterial inoculum, and bacteriostatic activity in liquid
      medium by M.I.C. values. The results provide a rational basis for the traditional
      antibacterial use of Hydrastis canadensis.

PMID- 11509984
TI  - Local anaesthetic activity of monoterpenes and phenylpropanes of essential oils.
AB  - The local anaesthetic activity of a number of compounds with different
      structures, contained in essential oils, was studied. Anaesthetic activity was
      evaluated in vivo in the rabbit conjunctival reflex test and in vitro in a rat
      phrenic nerve-hemidiaphragm technique. Among the substances tested terpineol and
      trans-anethole (10(-3) - 1 microg/ml) were able to drastically reduce the
      electrically evoked contractions of rat phrenic nerve-hemidiaphragm in a
      concentration-dependent manner, but not eugenol, (-)- and (+)-citronellal, (-)-
      and (+)-carvone, trans cinnamaldehyde and alpha-terpinene. In the rabbit
      conjunctival reflex test, the treatment with a solution of terpineol and trans
      anethole (10 - 100 microg/ml) effected a concentration-dependent increase in the
      number of stimuli required to evoke the reflex, thus confirming in vivo the local
      anaesthetic activity observed in vitro. Eugenol, (-)- and (+)-citronellal, trans
      cinnamaldehyde, (-)- and (+)-carvone and alpha-terpinene were as ineffective in
      the in vivo test as they were in the in vitro results.

PMID- 11509985
TI  - Vasorelaxant effects of the bioflavonoid chrysin in isolated rat aorta.
AB  - Chrysin relaxed the contractions induced by noradrenaline in isolated endothelium
      intact rat aortic rings (IC(50) = 16 +/- 4 microM). Endothelium removal and N(G)
      nitro-L-arginine methyl ester inhibited this relaxant effect. Chrysin potentiated
      the relaxation to acetylcholine under control conditions or after incubation with
      the superoxide anion generator hypoxanthine/xanthine oxidase. It also potentiated
      the relaxation induced by 3-morpholino-sydnonimine, sodium nitroprusside, and 8
      bromoguanosine-3':5'-cyclic-monophosphate. Therefore, vasorelaxation induced by
      chrysin in the rat aorta is endothelium- and NO-dependent. This effect is
      mediated by the prevention of O(2)(-)-induced inactivation of endothelial derived
      NO and also by the potentiation of cGMP-induced vasodilatation.

PMID- 11509986
TI  - Coronin from roots of Annona muricata, a putative intermediate in acetogenin
      biosynthesis (1).
AB  - A novel acetogenin, coronin, was isolated from the roots of Annona muricata L.
      The structure was elucidated by a combination of chemical and spectral methods
      including MS and NMR measurements. Coronin is probably an intermediate in the
      biosynthetic pathway of bis-tetrahydrofuran acetogenins, and is proposed as a
      biogenetic precursor of neoannonin-B.

PMID- 11509987
TI  - 2-substituted furans from Polyalthia suberosa.
AB  - Two new 2-substituted furans, 1-(2-furyl)pentacosa-16,18-diyne and 23-(2
      furyl)tricosa-5,7-diynoic acid, have been isolated from stems of Polyalthia
      suberosa. The structures were assigned by spectroscopic methods. The two
      compounds together with the previously reported kalasinamide, N-trans
      feruloyltyramine and N-trans-coumaroyltyramine showed anti-HIV activities.

PMID- 11509988
TI  - New naphthoquinones from Arnebia hispidissima roots.
AB  - Besides shikonin and arnebifuranone, two new shikonin esters isolated from the
      roots of Arnebia hispidissima have been characterized as butylshikonin and 2'
      methyl-hexa-1',3'-dienoylshikonin by physicochemical methods. Arnebifuranone is
      the first report from this species.

PMID- 11509989
TI  - A new alkaloid and other anti-implantation principles from Tabernaemontana
      heyneana.
AB  - A new alkaloid designated as ervatine, in addition to seven known alkaloids, viz.
      tabersonine, coronaridine, heyneanine, voacristine, voacristine
      hydroxyindolenine, hydroxyibogamine, and coronaridine hydroxyindolenine, were
      isolated from the fruit of Tabernaemontana heyneana Wall. Characterisation and
      structure elucidation of these compounds was made on the basis of their spectral
      analyses. The ethanolic extract and isolated alkaloids heyneanine and voacristine
      prevented pregnancy when administered during the preimplantation period in
      Sprague-Dawley rats. These were, however, found to possess significant
      uterotrophic activity.

PMID- 11509990
TI  - Essential oil composition and antimicrobial activity of three Zingiberaceae from
      S.Tome e Principe.
AB  - The essential oil composition of three Zingiberaceae widely used as medicinal
      aromatic plants from S. Tome and Principe: Aframomum danielli (Hook. f.) K.
      Schum., Curcuma longa L. and Zingiber officinale Rosc. was studied. Two samples
      of the essential oils from fruit of A. danielli and from rhizomes of the other
      two species, were obtained by hydrodistillation and analyzed by GC, GC-MS, and
      (13)C-NMR. The essential oil from fruits of A. danielli has been studied for the
      first time and was characterised by its high content of monoterpenes, with 1,8
      cineole (25.5 - 34.4 %) the major constituent, followed by beta-pinene (14.1 -
      15.2 %) and alpha-terpineol (9.9 - 12.1 %). Essential oils from the rhizomes of
      C. longa contained a lower content of ar-turmerone (4.0 - 12.8 %) than those
      reported in the literature for C. longa from other origins (24.7 - 31.4 %),
      whereas the results for Z. officinale essential oils were in accordance with the
      literature data. The essential oils of A. danielli and Z. officinale showed
      antimicrobial activity against all Gram-positive and Gram-negative bacteria
      tested, as well as against yeasts and filamentous fungi, using the agar diffusion
      method.

PMID- 11509991
TI  - A new guaianolide as apoptosis inhibitor from Chrysanthemum boreale.
AB  - The 8-O-acetyl-3,10-dihydroxy-4(15),11(13)-guaiadien-12,6-olide, named
      borenolide, was isolated from Chrysanthemum boreale M. Borenolide inhibits the
      etoposide-induced apoptosis in U937 cell with an IC(50) value of 6.2 microg/ml.
      Structural assignment was based on NMR-spectroscopic methods and X-ray
      crystallographic analysis.

PMID- 11509992
TI  - Direct amplification of length polymorphism analysis differentiates Panax ginseng
      from P. quinquefolius.
AB  - The method of direct amplification of length polymorphism (DALP) was applied to
      authenticate Panax ginseng and P. quinquefolius. A 636-bp DALP fragment was
      present in all P. ginseng but absent in all the P. quinquefolius cultivars
      examined. We have shown that the use of DALP and conversion of specific
      polymorphic band to sequence-tagged site (STS) for quick authentication may be
      applied to authenticate related medicinal materials.

PMID- 11509993
TI  - Two unusual oleanane saponins from Anemone anhuiensis.
AB  - From the rhizomes of Anemone anhuiensis (Ranunculaceae), two new triterpene
      saponins, anhuienosides A (1) and B (2), were isolated. These compounds are
      glycosylated at C-23 and their structures were elucidated as hederagenin 23-O
      beta-D-glucopyranosyl-(1-->2)-beta-D-glucopyranoside (1) and 23-O-beta-D
      glucopyranosyl-(1-->2)-beta-D-glucopyranosyl hederagenin 28-O-alpha-L
      rhamnopyranosyl(1-->4)-beta-D-glucopyranosyl(1-->6)-beta-D-glucopyranosyl ester
      (2) on the basis of chemical and spectral evidence.

PMID- 11509994
TI  - Maple syrup urine disease: identification and carrier-frequency determination of
      a novel founder mutation in the Ashkenazi Jewish population.
AB  - Maple syrup urine disease (MSUD) is a rare, autosomal recessive disorder of
      branched-chain amino acid metabolism. We noted that a large proportion (10 of 34)
      of families with MSUD that were followed in our clinic were of Ashkenazi Jewish
      (AJ) descent, leading us to search for a common mutation within this group. On
      the basis of genotyping data suggestive of a conserved haplotype at tightly
      linked markers on chromosome 6q14, the BCKDHB gene encoding the E1beta subunit
      was sequenced. Three novel mutations were identified in seven unrelated AJ
      patients with MSUD. The locations of the affected residues in the crystal
      structure of the E1beta subunit suggested possible mechanisms for the deleterious
      effects of these mutations. Large-scale population screening of AJ individuals
      for R183P, the mutation present in six of seven patients, revealed that the
      carrier frequency of the mutant allele was approximately 1/113; the patient not
      carrying R183P had a previously described homozygous mutation in the gene
      encoding the E2 subunit. These findings suggested that a limited number of
      mutations might underlie MSUD in the AJ population, potentially facilitating
      prenatal diagnosis and carrier detection of MSUD in this group.

PMID- 11509995
TI  - Mannose-binding lectin accelerates complement activation and increases serum
      killing of Neisseria meningitidis serogroup C.
AB  - The capacity for different lipo-oligosaccharide (LOS) sialylation patterns of
      Neisseria meningitidis serogroup C to influence the binding and function of the
      innate humoral component, mannose-binding lectin (MBL), was investigated. By use
      of flow cytometry and immunogold electron microscopy, a clinical isolate with
      reduced endogenous LOS sialylation was found to bind more MBL than did strains
      with higher endogenous sialylation. MBL binding was reduced but not ablated if
      the same strain was allowed to exogenously sialylate its LOS structures after
      incubation with cytidine-5'-monophospho-neuraminic acid. MBL binding led to an
      increased rate of complement activation, with enhanced deposition of the
      complement components C4 and C5b-9, and this correlated with an increase in
      bactericidal activity. LOS sialylation appears to be an important determinant of
      MBL binding to N. meningitidis and can modulate complement-dependent killing of
      the bacterium. These findings could explain the observed susceptibility to
      meningococcal disease of individuals genetically deficient in MBL.

PMID- 11509996
TI  - Antibody responses to bovine parainfluenza virus type 3 (PIV3) vaccination and
      human PIV3 infection in young infants.
AB  - A phase 2 clinical trial was conducted to evaluate the antibody responses to
      bovine parainfluenza virus type 3 (bPIV3) vaccination in young infants. Three
      groups were tested as follows: placebo (n=66) and 10(5) (n=64) or 10(6) (n=62)
      TCID(50) of bPIV3. The vaccine or placebo was administered intranasally at ages
      2, 4, 6, and 12-15 months, and serum specimens were collected at ages 2, 6, 7, 12
      15, and 13-16 months. Serum hemagglutination inhibition (HI) and IgA antibody
      titers against bPIV3 and human PIV3 (hPIV3) were measured. The results indicate
      that antibody responses to bPIV3 vaccination are more likely to be detected by
      the bPIV3 IgA and HI assays than by the hPIV3 IgA and HI assays, that bPIV3
      induced antibody response can be differentiated from hPIV3-induced antibody
      response most reliably by comparing bPIV3 and hPIV3 HI titers, and that bPIV3
      vaccine prevents vaccine recipients from developing antibody profiles of hPIV3
      primary infection.

PMID- 11509997
TI  - Evidence for superantigen involvement in severe group a streptococcal tissue
      infections.
AB  - Host-pathogen interactions were studied in tissue biopsy samples from patients
      with severe invasive group A streptococcus (GAS) infections. Skin, subcutaneous
      tissue, and fascia biopsy samples were divided into clinical grade 1 (no evidence
      of inflammation [n=7]) or clinical grade 2 (inflamed tissue--erythema and edema
      including cellulitis, fasciitis, and necrotizing fasciitis [n=24]). In situ
      imaging demonstrated significantly higher bacterial load in biopsy samples of
      higher clinical grade (P<.05), and the bacterial load correlated with the in vivo
      expression of the superantigen streptococcal pyrogenic exotoxin F (P<.02).
      Increased expression of the interleukin-1 cytokines and significantly higher
      expression of tumor necrosis factor-beta, interferon-gamma, and the homing
      receptors CC chemokine receptor 5, CD44, and cutaneous lymphocyte-associated
      antigen (P<.002-.05) were observed in biopsy samples of higher clinical grade.
      Thus, the cytokine profile at the local site of infection mimics that of a
      typical superantigen cytokine response. The findings of this study demonstrate a
      critical role for superantigens and Th1 cytokines in GAS tissue infections.

PMID- 11509998
TI  - Effectiveness of hepatitis B vaccination in babies born to hepatitis B surface
      antigen-positive mothers in Italy.
AB  - This study examined 522 children born to hepatitis B surface antigen (HBsAg)
      positive mothers from 1985 through 1994 and evaluated the protection provided by
      anti-hepatitis B virus (HBV) immunization at birth. Babies were given hepatitis B
      immunoglobulin and hepatitis B vaccine at birth. At 5-14 years after
      immunization, 17 children (3.3%) were anti-HB core antigen positive, and 3 also
      were HBsAg positive. One carrier child had a double mutation, with substitution
      of proline-->serine at codons 120 (P120S) and 127 (P127S) within the a
      determinant of HBsAg. Of the 522 children, 400 (79.2%) of 505 still had
      protective anti-HBsAg titers > or =10 mIU/mL. Thus, HBV vaccination of children
      born to HBsAg-positive mothers is effective and confers long-term immunity. There
      is no evidence that the emergence of HBV escape mutants secondary to the immune
      pressure against wild-type HBV is of concern.

PMID- 11509999
TI  - Impact of human immunodeficiency virus type 1 (hiv-1) subtype on women receiving
      single-dose nevirapine prophylaxis to prevent hiv-1 vertical transmission (hiv
      network for prevention trials 012 study).
AB  - In Uganda, the HIV Network for Prevention Trials (HIVNET) 012 study recently
      demonstrated that single-dose nevirapine (Nvp) prophylaxis is effective for
      preventing mother-to-child transmission (MTCT) of human immunodeficiency virus
      type 1 (HIV-1). This exploratory study examines the relationship between HIV-1
      subtype, MTCT, and the development of Nvp resistance (Nvp(R)) in women enrolled
      in HIVNET 012. For 102 women (32 whose infants were HIV-1 infected by age 6-8
      weeks and 70 whose infants were uninfected), HIV-1 subtypes included 50 (49%)
      subtype A, 35 (34%) subtype D, 4 (4%) subtype C, 12 (12%) recombinant subtype,
      and 1 unclassified. There was no apparent difference in the rate of MTCT among
      women with subtype A versus D (adjusted odds ratio [OR], 1.24; 95% confidence
      interval [CI], 0.45-3.43). Nvp(R) mutations were detected more frequently at 6-8
      weeks postpartum in women with subtype D than in women with subtype A (adjusted
      OR, 4.94; 95% CI, 1.21-20.22). Additional studies are needed to further define
      the relationship between HIV-1 subtype and Nvp(R) among women receiving Nvp
      prophylaxis.

PMID- 11510000
TI  - Genetic and evolutionary analysis of mutations in the gusA gene that cause the
      absence of beta-glucuronidase activity in Escherichia coli O157:H7.
AB  - Escherichia coli serotype O157:H7 do not exhibit beta-glucuronidase (GUD)
      activity but carry the gusA gene (uidA) that encodes for GUD. In trans
      complementation, the gusA gene cloned from the GUD-positive variant strain 493-89
      effectively restored GUD activity in O157:H7 strain 35150. Comparison of gusA
      sequences from the GUD-negative 35150 strain to that of 493-89 revealed several
      base mutations, including a guanosine (G) dinucleotide insertion that caused a
      frameshift in the 35150 gusA gene and introduced a predicted premature
      termination codon. This explains the absence of GUD activity in O157:H7. A 35150
      gusA construct from which the G-G insertion was deleted restored activity in GUD
      negative O157:H7 transformants. The G-G insertion was present in all GUD-negative
      O157:H7 strains but was absent in their GUD-positive variants. The G-G insertion
      that produced the characteristic GUD-negative phenotype to O157:H7 strains
      appeared later than the other gusA mutations in the evolutionary emergence of
      O157:H7.

PMID- 11510001
TI  - Nodular fasciitis of the external ear region: a clinicopathologic study of 50
      cases.
AB  - Nodular fasciitis (NF), uncommon in the auricular area, is a benign reactive
      myofibroblastic proliferation that may be mistaken for a neoplastic
      proliferation. Fifty cases of NF of the auricular region were identified in the
      files of the Otorhinolaryngic-Head and Neck Tumor Registry of the Armed Forces
      Institute of Pathology. The patients included 22 females and 28 males, aged 1 to
      76 years (mean, 27.4 years). The patients usually presented clinically with a
      mass lesion (n = 49). Five patients recalled antecedent trauma. The lesions were
      dermal (n = 28) or subcutaneous (n = 11) in those cases where histologic
      determination was possible, measuring 1.9 cm on average. The majority of the
      lesions were circumscribed (n = 38), composed of spindle-shaped to stellate
      myofibroblasts arranged in a storiform growth pattern, juxtaposed to hypocellular
      myxoid tissue-culture-like areas with extravasation of erythrocytes. Dense,
      keloid-like collagen and occasional giant cells were seen (n = 18). Mitotic
      figures (without atypical forms) were readily identifiable. By
      immunohistochemical staining, myofibroblasts were reactive with vimentin, actins,
      and CD68. All patients had surgical excision. Four patients (9.3%) developed
      local recurrence and were alive and disease free at last follow-up. All patients
      with follow-up (n = 43) were alive or had died of unrelated causes, without
      evidence of disease an average 13.4 years after diagnosis. Nodular fasciitis of
      the auricular area occurs most often in young patients. Because NF is more often
      dermally situated than extremity NF, it may present with superficial ulceration
      and/or bleeding. Local recurrence is more frequent because of the difficulty in
      obtaining complete surgical excision around the ear.

PMID- 11510002
TI  - Pleomorphic rhabdomyosarcoma in children: four cases in the pediatric age group.
AB  - Pleomorphic rhabdomyosarcoma is considered rare and controversial, especially in
      children. Although pleomorphic rhabdomyosarcoma has been observed in children,
      its sparcity has taken it out of current childhood rhabdomyosarcoma
      classifications. We report four pediatric cases of pleomorphic rhabdomyosarcoma,
      review morphologic, immunohistochemical, and ultrastructural features, and
      discuss the rare need to include this category in children. The Soft Tissue
      Registry of the Armed Forces Institute of Pathology was searched for cases coded
      as "pleomorphic rhabdomyosarcoma" from 1970 to the present. Only cases in
      patients less than 21 years old were included. Clinical data, morphology, and
      immunohistochemical stains were reviewed and follow-up was obtained. Electron
      microscopy was performed on two cases. Molecular analysis by polymerase chain
      reaction was performed on one case with available material. Of four patients
      included, there were three boys and one girl. Patient ages ranged from 9 months
      to 10 years (median, 4.5 years). Tumors were located on the chest wall (n = 2)
      and one each on the upper and lower extremities. Tumor size ranged from 4.0 to
      10.0 cm (median, 7 cm). Grossly, the tumors were lobulated and circumscribed.
      Microscopically, architectural patterns varied from solid to fascicular or
      storiform. All tumors had large, often multinucleated, polygonal, spindled or
      strap-like rhabdomyoblasts with abundant eosinophilic cytoplasm. Nuclear
      characteristics ranged from hyperchromatic to vesicular. Most tumor cells had
      large prominent nucleoli. Background rhabdomyoblasts varied from spindled to
      polygonal. No tumors displayed areas typical of embryonal or alveolar
      rhabdomyosarcoma. All tumors exhibited atypical mitotic figures.
      Immunohistochemistry revealed that the tumors were positive for the following
      markers: desmin (3/4), myoglobin (4/4), myoD1 (3/3), myf4 (3/3), and MSA (4/4).
      The two cases studied by electron microscopy both showed evidence for skeletal
      muscle differentiation. One case showed no evidence for a t(2;13) or t(1;13)
      translocation. Two patients were alive with no evidence of disease at 12 and 25
      years. One patient was dead of disease at 9 years. Pleomorphic rhabdomyosarcoma
      is rare but exists in children. The diagnosis should be considered in pleomorphic
      sarcomas exhibiting skeletal muscle differentiation, which are otherwise devoid
      of typical areas or chromosomal changes of embryonal or alveolar
      rhabdomyosarcoma.

PMID- 11510003
TI  - Oral spindle cell lipoma.
AB  - Lipoma is an uncommon benign, oral, soft-tissue neoplasm commonly found on the
      buccal mucosa. It is predominantly composed of mature fat with or without other
      mesenchymal tissue elements, showing a variety of histologic subtypes, one of
      which is the rare "spindle cell variant" with only nine previously reported cases
      in the English literature. In this report, we review clinical and
      histomorphologic data of 164 cases of oral lipomas retrieved from the files of
      Long Island Jewish Medical Center, Department of Dental Medicine (New Hyde Park,
      NY). Of these, only two cases were diagnosed as the spindle cell variant, further
      confirming the rarity of this histologic subtype. A review of oral lipoma with
      particular reference to the spindle cell variant is also presented.

PMID- 11510004
TI  - Pulmonary spindle cell lesions: correlation of aspiration cytopathology and
      histopathology.
AB  - Spindle cell lesions primary to the lung are uncommon. They encompass a range of
      entities that are sometimes benign, but more often represent malignancies. The
      cytopathology of these lesions, obtained using fine-needle aspiration biopsy,
      remain incompletely described. Correlation of fine-needle aspiration smears with
      tissue sections show relatively faithful reproduction between the two. The
      overlapping features seen in tissue preparations of these various lesions,
      however, appears to be magnified in aspirates such that specific diagnoses are
      less often possible in the latter without immunophenotyping, and occasionally
      distinction between benign and malignant lesions may be difficult. This review
      seeks to correlate the salient cyto- and histo-morphologic features of spindled
      pulmonary lesions, and to cite the limitations and advantages of aspiration
      cytopathology in analysis of these lesions.

PMID- 11510005
TI  - Pleural amyloidosis mimicking mesothelioma: a clinicopathologic study of two
      cases.
AB  - Two cases of pleural amyloidosis are presented. The patients are two men, 70 and
      72 years of age respectively. Neither patient had evidence of systemic
      amyloidosis. Each presented clinically with symptoms of chest pain and dyspnea.
      Radiologically, both patients showed diffuse pleural thickening similar to that
      observed in malignant mesothelioma. In both patients, surgical decortication of
      the pleura was performed. Histologically, the lesions were characterized by the
      presence of an amorphous eosinophilic material with focal collections of a
      lymphoplasmacytic infiltrate. Focal clusters of giant cells were admixed with the
      lymphoplasmacytic infiltrate. Histochemical stains for Congo red showed strong
      positive apple-green birefringency. Immunohistochemical studies using kappa and
      lambda light chains showed polyclonality. The cases discussed herein represent an
      unusual presentation of amyloid and one that needs to be considered in the
      differential diagnosis of malignant mesothelioma.

PMID- 11510006
TI  - Basaloid squamous carcinoma with collagenous spherules and crystalloids.
AB  - A case of basaloid squamous carcinoma with unusual spheruloid and crystalloid
      structures occurring in the left submandibular region of 45-year-old woman is
      described. The tumor displayed features typical of basaloid squamous carcinoma.
      In addition, there were numerous eosinophilic deposits of extracellular matrix,
      which reacted positively on periodic acid-Schiff staining. These deposits were
      arranged in lamellar concentric and radial patterns. Ultrastructurally, they were
      composed of extracellular matrix components rich in basement membrane substances.
      A few banded collagen fibers were found in some deposits. Basaloid squamous
      carcinoma is an aggressive variant of squamous cell carcinoma, with a
      predilection to the head and neck region, that needs to be distinguished from
      other tumors that may contain abundant deposits of basement membrane rich
      material, especially from adenoid cystic carcinoma.

PMID- 11510007
TI  - Combined large cell neuroendocrine carcinoma and spindle cell carcinoma of the
      lung.
AB  - We report a unique case of a combined pulmonary large-cell neuroendocrine
      carcinoma and spindle-cell carcinoma. The patient was a 54-year-old female smoker
      who presented with a 4-month history of increased left-sided chest pain and
      exertional dyspnea. The left upper lobectomy specimen revealed an 8.0-cm mass
      with central necrosis. Microscopically, the epithelial areas were composed of
      well-defined nests of large cells with peripheral palisading expressing low
      molecular-weight keratin, synaptophysin, chromogranin, and neuron-specific
      enolase. The spindle-cell component consisted of pleomorphic cells arranged in
      fibrosarcoma and malignant fibrous histiocytoma-like patterns. These spindle
      cells were positive for low-molecular-weight keratin and vimentin with focal
      expression of CD68 and muscle-specific actin. Electron microscopy in the spindle
      cell areas showed cell junctions and numerous tonofilaments, indicative of
      epithelial differentiation. The tumor behaved aggressively and the patient died
      with extensive metastases 4 months after surgery. The combination of
      neuroendocrine malignancies and spindle-cell carcinomas appears to be uncommon in
      the lung. Previous reports have described this association in single case reports
      of anaplastic small-cell carcinoma and atypical carcinoid, but not in large-cell
      neuroendocrine carcinoma.

PMID- 11510008
TI  - Extranodal marginal-zone B-cell lymphoma of the salivary gland.
AB  - Primary non-Hodgkin's lymphoma of the salivary gland is an uncommon tumor that
      most often occurs in the parotid gland. The most common subtype is marginal-zone
      B-cell lymphoma, extranodal, mucosa-associated lymphoid tissue type. This subtype
      has recently been included in the Revised European-American Classification of
      Lymphoid Neoplasms, as well as in the upcoming World Health Organization
      classification of hematopoietic and lymphoid neoplasms. This low-grade lymphoma
      usually arises in a background of benign lymphoepithelial lesion or myoepithelial
      sialadenitis that is associated with the autoimmune disease Sjogren's syndrome.
      It occasionally develops in patients who do not have a history of autoimmune
      disease. When mucosa-associated lymphoid tissue lymphoma occurs in the salivary
      gland, as in other extranodal sites such as the stomach, it is usually an
      indolent neoplasm that tends to remain localized for long periods of time, even
      without treatment. Eventually, however, the tumor may disseminate or transform to
      a higher grade. The histologic distinction of myoepithelial sialadenitis from low
      grade B-cell mucosa-associated lymphoid tissue lymphoma can be a difficult
      diagnostic challenge and many of these lesions continue to be ambiguously
      diagnosed as "pseudolymphoma." Immunophenotypic or flow cytometric analysis may
      be useful in showing an aberrant phenotype or immunoglobulin light-chain
      restriction, which helps to support a diagnosis of malignant lymphoma in most
      cases. Molecular genetic analysis for immunoglobulin gene rearrangements also may
      be useful in showing monoclonality, although the exact significance of this
      finding in some cases remains controversial.

PMID- 11510009
TI  - Liver transplantation for hereditary hemochromatosis.
AB  - Although hereditary hemochromatosis (HHC) is relatively common, it is an uncommon
      indication for orthotopic liver transplantation (OLT). The diagnosis of HHC in
      patients with end-stage liver disease is difficult because many of these patients
      have elevated serum and tissue iron levels. Of patients undergoing OLT with iron
      stores in the range typical for HHC, approximately 10% are homozygous for the
      C282Y mutation. Most studies published to date noted decreased survival in
      patients who underwent OLT for HHC compared with those who underwent OLT for
      other indications. Death in patients with HHC was caused by increased infectious
      and cardiac complications. Decreased post-OLT survival in patients with iron
      overload appears to be independent of HFE gene status. This suggests that
      regardless of the cause, iron overload may be detrimental in patients undergoing
      OLT. Follow-up of patients undergoing OLT for HHC and case reports of the
      inadvertent transplantation of a liver from a donor with HHC has furthered our
      understanding of the pathophysiological state of iron overload in HHC.

PMID- 11510010
TI  - Reconstruction of double hepatic arterial and portal venous branches for right
      lobe living donor liver transplantation.
AB  - Double hepatic arterial and portal venous branches are common anatomic variations
      of the isolated right hepatic lobe. Reconstruction of these vessels during
      transplantation can be challenging because of their small caliber, close
      proximity to other hilar structures, and abnormal alignment with the native
      vasculature. Practical techniques for the creation of these anastomoses would
      simplify the recipient surgery and might minimize the incidence of vascular
      complications. Alternative methods for management of these structures are
      summarized. The recipient's proper hepatic artery and its bifurcation are
      resected for use as an arterial Y-type graft. The donor arteries are individually
      anastomosed at the bifurcation of the recipient's hepatic artery at the back
      table. The free end of the Y graft is then replaced at the origin of the
      gastroduodenal artery using standard branch-patch technique. Reconstruction of a
      second donor portal branch is similarly facilitated by ex situ placement of a Y
      type vascular conduit derived from the recipient's portal vein. Surgical
      management of these vessels and reconstruction of other hilar structures are
      noticeably less cumbersome. There have been no short-term vascular complications.
      The use of autologous vascular conduits with ex situ reconstruction facilitates
      management of double donor arterial and portal venous branches. The incidence of
      complications attributable to these methods is expected to be low.

PMID- 11510011
TI  - Adult-to-adult living donor liver transplantation using right-lobe grafts:
      results and lessons learned from a single-center experience.
AB  - Living donor liver transplantation (LDLT) for adults is now a practical
      alternative to cadaveric liver transplantation. Use of right-lobe grafts has
      become the preferred donor procedure. Because of the complexity of this
      operation, a learning curve is to be expected. We report the outcome of our first
      41 LDLTs at the University of Colorado Health Sciences Center (Denver, CO). We
      also discuss the lessons learned and the resultant modifications in the procedure
      that evolved during our series. Patient records were retrospectively reviewed
      between August 1997 and February 2001 for the following end points: recipient
      survival, graft survival, and donor and recipient complications. Thirty-eight of
      41 living donor liver transplant recipients (93%) are alive and well
      postoperatively with a mean follow-up of 9.6 months. Four patients required
      retransplantation secondary to technical problems (9.8%); all 4 patients were in
      our initial 11 cases. Modification of the donor liver plane of transection
      resulted in venous outflow improvement. Also, biliary management was modified
      during the series. Donor complications are listed; all 41 donors have returned to
      normal pretransplantation activity. Our results indicate that LDLT can be
      performed safely with excellent donor and recipient outcomes. Dissemination of
      our experience can help shorten the learning curve for other institutions.

PMID- 11510012
TI  - Accuracy and utility of 3-dimensional computed tomography in evaluating donors
      for adult living related liver transplants.
AB  - Three-dimensional (3D) computed tomography (CT) is an imaging technique that
      renders anatomic detail in 3D images from helical computed tomographic scans. The
      purpose of this study is to assess 3D CT in the preoperative evaluation of adult
      living related liver transplant donors. Nine patients underwent right-lobe liver
      resection for adult living related liver transplants between October 1999 and
      September 2000. All donors underwent triphasic helical CT of the liver with 3D
      computed tomographic reconstruction and conventional angiography. The 3D images
      were correlated with angiography and intraoperative findings. The origin of
      vessels, relative length of segments, and position of branches were considered
      for accuracy. The 3D computed tomographic images were compared with angiograms to
      determine whether angiography could be replaced by 3D CT. 3D CT identified all
      variations of the hepatic vein confluences and portal vein trifurcations and all
      hepatic arterial variants. At surgery, the 3D computed tomographic images of
      hepatic and portal veins were judged to be accurate and helpful in 8 of 9 cases,
      and images of the hepatic artery, accurate and helpful in 5 of 9 cases. The 3D
      computed tomographic images of hepatic and portal veins were better than or
      equivalent to angiograms in nearly all cases. The 3D computed tomographic images
      of the hepatic artery were better than or equivalent to angiography in 5 of 9
      cases. By providing an accurate 3D map of the liver and its vasculature, 3D
      computed tomographic reconstructions of the hepatic vasculature are a useful
      adjunct for surgical planning in adult living related liver donors. 3D CT clearly
      delineates portal and hepatic veins as well as or better than the angiogram and
      can identify the hepatic artery and its branches well enough to consider
      replacing angiography, thus reducing cost, inconvenience, and risk to the donor.

PMID- 11510013
TI  - Steroid-free liver transplantation using rabbit antithymocyte globulin induction:
      results of a prospective randomized trial.
AB  - Steroids have been 1 of the primary modes of immunosuppression since the
      inception of transplantation and have been credited with both the prevention and
      treatment of rejection. Steroids also have been held responsible for increased
      infections, posttransplantation diabetes, and recurrent hepatitis after
      orthotopic liver transplantation (OLT). The purpose of this ongoing prospective
      randomized trial is to eliminate steroid use in OLT through induction with rabbit
      antithymocyte globulin (RATG). This is the first report of a prospective
      randomized trial in OLT achieving complete absence of steroids. Seventy-one adult
      patients were prospectively randomized to administration of RATG or steroids.
      Thirty-six patients were randomized to the administration of RATG induction at a
      dose of 1.5 mg/kg intravenously (IV) beginning during the anhepatic phase. No
      steroids were administered. Patients were administered a second 1.5-mg/kg dose of
      RATG post-OLT day 1. Thirty-five patients were randomized to the administration
      of methylprednisolone, which had been our standard immunosuppressive protocol.
      These patients were administered methylprednisolone, 1,000 mg IV, initiated
      during the anhepatic phase and followed by steroid taper. Maintenance
      immunosuppression consisted of tacrolimus and mycophenolate, with or without
      prednisone. Three patients died in each group, for an overall survival rate of
      91% in each group. One patient in each group required re-OLT, for a graft
      survival rate of 89% in each group. Seven patients administered RATG had biopsy
      proven rejection (20.5%), all of whom were successfully treated by increasing
      tacrolimus doses. Eleven patients administered steroid had biopsy-proven
      rejection (32%), 7 (64%) of whom required additional steroids for treatment,
      whereas 4 patients (36%) were successfully treated by increasing tacrolimus
      doses. The incidence of rejection was not statistically significant; however,
      there was a significant difference in the incidence of steroid-requiring
      rejection (P =.01). The incidence of recurrent hepatitis C was 50% in RATG
      patients and 71% in steroid patients (P = not significant). The incidence and
      severity of infectious complications were slightly lower in RATG patients,
      accounted for by a greater incidence of cytomegalovirus (CMV) infection in the
      steroid patients. RATG induction enables complete avoidance of steroid use in OLT
      with a trend toward a lower rejection rate, decreased incidence of post-OLT
      diabetes and recurrent hepatitis C, and decreased CMV infection. This prospective
      randomized trial gives encouraging support that steroids can be safely eliminated
      in OLT.

PMID- 11510014
TI  - Steroid-free immunosuppression: balancing efficacy and toxicity.

PMID- 11510015
TI  - Orthotopic liver transplantation using low-dose tacrolimus and sirolimus.
AB  - Although sirolimus (SRL) binds the immunophilin FK506-binding protein-12 (FKBP
      12) with greater avidity than tacrolimus (TAC), animal studies have shown that
      SRL and TAC act synergistically to prevent rejection. Dose-related toxicity is
      more often the cause of TAC discontinuation than rejection. We hypothesized that
      SRL would allow for a substantial reduction in the concomitant dose of TAC after
      liver transplantation to levels less than the threshold for toxicity. A series of
      56 liver transplant recipients were administered a combination of SRL and TAC
      (target trough levels, 7 and 5 ng/mL, respectively). Planned weaning of steroids
      commenced after 3 months. Pharmacokinetic (PK) studies were undertaken. Patient
      and graft survival were 52 patients (93%) and 51 grafts (91%), with a follow-up
      of 23 months (range, 6 to 35 months). One episode (1.8%) of hepatic artery
      thrombosis was seen. The rate of acute cellular rejection was 14%. No extra
      treatment was administered in 3 of 8 patients, and the other 5 episodes responded
      to a single course of steroids. Cytomegalovirus infection occurred in 4 patients
      (7%). Renal function, glucose control, and lipid metabolism are near normal in 47
      patients (84%) without additional medication. Steroid elimination is completed in
      51 patients (91%). Bioavailability of SRL and TAC varied between transplant
      recipients, but trough levels strongly correlated with the area under the curve
      (r(2) = 0.82 and r(2) = 0.84, respectively). Simultaneous administration did not
      affect the PK profile of the drugs at this dose. The ratio of trough level to
      daily dose correlated between SRL and TAC. The synergistic effect seen in animal
      models also occurs in clinical liver transplant recipients on SRL-TAC combination
      immunosuppression. A low-dose combination of SRL and TAC should be compared with
      conventional immunosuppression in a multicenter, randomized, controlled trial.

PMID- 11510016
TI  - Cerebral blood flow velocity increases during a single treatment with the
      molecular adsorbents recirculating system in patients with acute on chronic liver
      failure.
AB  - The aim of this uncontrolled pilot study is to determine the effect of treatment
      with the molecular adsorbents recirculating system (MARS) on cerebral perfusion
      in patients with acute on chronic liver failure (AOCLF). In 8 patients (median
      age, 44 years; range, 35 to 52 years) admitted with AOCLF, a single 10-hour MARS
      treatment was performed. Hepatic encephalopathy (HE) was graded according to the
      Fogarty criteria. Changes in cerebral perfusion were determined by transcranial
      Doppler as mean flow velocity (V(mean)) in the middle cerebral artery. Arterial
      ammonia and bilirubin levels were monitored as a measure of the capability of the
      MARS to remove water-soluble and protein-bound toxins. During MARS treatment, HE
      grade improved in 3 patients and remained unchanged in 5 patients (P =.11).
      V(mean) increased from 42 cm/sec (range, 26 to 59 cm/sec) to 72 cm/sec (range, 52
      to 106 cm/sec; P <.05), whereas arterial ammonia level decreased from 88
      micromol/L (range, 45 to 117 micromol/L) to 71 micromol/L (range, 26 to 98
      micromol/L; P <.05) and bilirubin level from 537 micromol/L (range, 324 to 877
      micromol/L) to 351 micromol/L (range, 228 to 512 micromol/L; P <.05). In
      conclusion, cerebral perfusion is increased and levels of ammonia and bilirubin
      are reduced during MARS treatment in patients with AOCLF.

PMID- 11510017
TI  - Improvement in cerebral perfusion after MARS therapy: further clues about the
      pathogenesis of hepatic encephalopathy?

PMID- 11510018
TI  - T-cell clones derived by CD3 stimulation from hepatitis C virus explanted liver
      tissue are not representative of dominant clones present in vivo.
AB  - Liver tissue from hepatitis C virus (HCV)-related end-stage disease contains T
      cell infiltrates. The goal of this study is to determine whether CD4 T-cell
      clones established in vitro using an antigen-independent technique from explanted
      liver tissue (n = 3) are representative of dominant clones present in vivo. T
      cell receptor (TCR) use by intrahepatic CD4 T cells was assessed by spectratype
      analysis. Clones were established from single CD4 T cells by culturing in vitro
      with anti-CD3 and interleukin-2 (n > 25 per patient). TCR genes expressed by each
      clone were identified by sequencing. When identical clones were isolated, the
      original spectratype was analyzed further to determine whether the clone was a
      dominant T-cell expansion in vivo. Evidence for clonal expansions was found in
      all patients by spectratyping. T cells expressing the same TCRBV genes used for
      spectratyping were cloned in vitro. Duplicate clones expressing the same TCR
      genes were observed in 2 patients. Confirmation that clones established in vitro
      matched those present in vivo was obtained for 2 clones. Many dominant clones
      identified by spectratyping did not proliferate in vitro. Although spectratyping
      suggested the widespread accumulation of clonal expansions in HCV-related end
      stage liver disease, clones established in vitro using anti-CD3 were poorly
      representative of dominant clones present in vivo. Although cloning with anti-CD3
      has the advantage of generating T-cell clones not biased a priori toward a
      specific antigen, modified cloning strategies will need to be developed to expand
      those clones that appear dominant in end-stage organs.

PMID- 11510019
TI  - Outcome of liver transplantation for hepatitis B: report of a single center's
      experience.
AB  - Results of liver transplantation (LT) for hepatitis B have improved significantly
      with the use of hepatitis B immune globulin (HBIG) and/or lamivudine. The aim of
      this study is to review the long-term outcome of patients who underwent LT for
      hepatitis B. Records of 41 patients who underwent LT for hepatitis B and survived
      3 months or longer post-LT were reviewed. Twenty patients were administered no
      immunoprophylaxis or short-term intramuscular HBIG, whereas 21 patients were
      administered high-dose intravenous (IV) HBIG. Median post-LT follow-up in these 2
      groups was 76 months (range, 4 to 155 months) and 25 months (range, 4 to 68
      months), respectively. Hepatitis B recurred in 15 (75%) and 4 patients (19%) who
      underwent LT in the pre-HBIG and post-HBIG eras, respectively. Cumulative rates
      of recurrent hepatitis B at 1 and 3 years post-LT in these 2 groups were 66% and
      77% and 20% and 20%, respectively (P <.001). Recurrent hepatitis B in the post
      HBIG era correlated with antibody to hepatitis B surface antigen titer less than
      100 IU/L. Nine patients with recurrent hepatitis B were administered lamivudine
      for 13 to 49 months (median, 28 months); 6 patients continued to have stable or
      improved liver disease, whereas 3 patients developed virological breakthrough
      with slow deterioration of liver disease. Long-term IV HBIG is effective in
      preventing recurrent hepatitis B. The risk for recurrent hepatitis B is
      negligible after the first year post-LT. Among patients with no virological
      breakthrough, lamivudine can stabilize or improve liver disease for up to 4 years
      in patients with recurrent hepatitis B post-LT.

PMID- 11510020
TI  - Temporal profile of total, bound, and free Gc-globulin after acetaminophen
      overdose.
AB  - Low admission values of the actin scavenger Gc-globulin are associated with an
      adverse outcome in acetaminophen (paracetamol) overdose. This prospective
      longitudinal study including 84 patients with acetaminophen overdose
      characterizes the temporal profile of Gc-globulin during the entire length of
      hospitalization. Serum Gc-globulin (total, actin bound, and free) levels and
      actin-complex ratio were measured on admission and every 12 hours until
      discharge. In 32 patients without hepatotoxicity (non-HEPTOX group; peak
      transaminase levels < 1,000 U/L), total and free Gc-globulin levels and complex
      ratio remained within normal range during hospitalization. Among 52 patients with
      hepatotoxicity (HEPTOX group; peak transaminase levels > 1,000 U/L), 15 patients
      had hepatic encephalopathy (HE), and 37 patients did not. In these 2 groups,
      total and free Gc-globulin levels decreased to 97 and 50 mg/L and 148 and 86
      mg/L, respectively (normal mean, 340 and 299 mg/L), the nadir occurring at 72
      hours postoverdose. Complex ratio peaked at 60 hours at levels more than 3-fold
      greater than normal. Conversely, bound Gc-globulin remained within normal levels
      for all patients throughout the observation period. At day 2, a total Gc-globulin
      cutoff value of less than 120 mg/L correctly predicted HE in 75%, and a value
      greater than 120 mg/L correctly predicted the absence of HE in 91% of patients.
      In conclusion, Gc-globulin is severely stressed in patients with hepatotoxicity.
      Extreme values occurred at 60 to 72 hours postoverdose, a period in which Gc
      globulin protection against actin toxicity may be inadequate. A total Gc-globulin
      level less than 120 mg/L on day 2 is a good predictor of later HE. Bound Gc
      globulin is maintained at constant levels independent of total Gc-globulin
      levels, suggesting a balanced upregulation of the removal of bound Gc-globulin
      even under conditions with increased actin release.

PMID- 11510021
TI  - The effect of selective bowel decontamination on the pharmacokinetics of
      mycophenolate mofetil in liver transplant recipients.
AB  - Mycophenolate mofetil (MMF) is a prodrug immunosuppressant with a high oral
      bioavailability. Enterohepatic cycling of a glucuronide derivative of MMF
      contributes substantially to the bioavailability, but is dependent on bacterial
      deglucuronidation by intestinal flora. This study aims to determine whether an
      antibiotic regimen with activity against such organisms reduces the
      bioavailability of MMF by impairing enterohepatic cycling. In a prospective
      trial, 6 liver transplant recipients were administered MMF and a 21-day
      antibiotic regimen for selective bowel decontamination (SBD). Time-concentration
      profiles of the pharmacologically active metabolite, mycophenolic acid (MPA),
      were obtained during and after the SBD regimen. The bioavailability of MPA was
      reduced during compared with after the regimen (14.5 +/- 3.5 v 21.1 +/- 9.8 mg.
      h/mL; P =.07). The most pronounced contribution to this reduction was observed
      from 6 hours onward (2.4 +/- 1.4 v 5.6 +/- 4.4 mg. h/mL; P <.05). The presence of
      secondary maxima in the time-concentration profiles of MPA after, but not during,
      SBD indicates that enterohepatic cycling may be inhibited during SBD and restored
      afterward. Enterohepatic cycling may contribute 7% to 54% (mean, 29%) of the
      bioavailability of MPA. We conclude that the bioavailability of MMF may be
      reduced when SBD is used, and the reduction is likely to result from the
      interruption of enterohepatic cycling. This mechanism should be taken into
      consideration not only during SBD, but in any clinical setting combining MMF and
      broad-spectrum antibiotics.

PMID- 11510022
TI  - Imaging findings in Budd-Chiari syndrome.

PMID- 11510023
TI  - Liver transplantation in patients with severe portopulmonary hypertension treated
      with preoperative chronic intravenous epoprostenol.
AB  - Portopulmonary hypertension (PPHTN) is no longer an absolute contraindication to
      orthotopic liver transplantation (OLT). The pre-OLT management of patients with
      PPHTN requires early diagnosis and chronic therapy with intravenous epoprostenol
      to decrease pulmonary vascular resistance (PVR). Close follow-up is necessary to
      reassess pulmonary artery pressures (PAPs) and evaluate right ventricular (RV)
      function. This assists in the optimal timing of OLT. Successful management also
      necessitates reassessment of pulmonary artery hemodynamics just before OLT, with
      clearly defined parameters used to determine whether to proceed. Even with the
      intraoperative and postoperative availability of potent pulmonary vasodilators,
      clinical management may be suboptimal in reducing PAP. Adequate reduction in PVR
      and improvement in RV function in response to chronic epoprostenol therapy may
      facilitate successful OLT. We present a case report and review the limited
      experience with this treatment.

PMID- 11510024
TI  - Pneumocystis carinii pneumonia prophylaxis with atovaquone in trimethoprim
      sulfamethoxazole-intolerant orthotopic liver transplant patients: a preliminary
      study.
AB  - Pneumocystis carinii pneumonia (PCP) is an opportunistic infection associated
      with increased morbidity and mortality in solid-organ and bone-marrow transplant
      recipients. Side effects of trimethoprim-sulfamethoxazole (TMP/SMX) are frequent;
      therefore, we performed a preliminary study using atovaquone suspension, 750 mg
      once daily, for 1 year for the prevention of PCP in liver transplant recipients
      intolerant to TMP/SMX therapy. Twenty-eight patients were treated, and data were
      analyzed for efficacy and toxicity. Adverse events occurred in 14 subjects,
      mainly related to the gastrointestinal tract. Side effects from TMP/SMX, i.e.,
      rash, completely resolved and bone-marrow suppression improved in 62% of
      patients. No patients developed Pneumocystis carinii infection. Although a lower
      dose of atovaquone once daily may be effective in transplant recipients, further
      studies are necessary to confirm this preliminary observation. Liver Transpl
      2001;7:750-751.)

PMID- 11510026
TI  - Gemcitabine-containing regimens in bladder cancer: A new standard of care.

PMID- 11510027
TI  - Gemcitabine and carboplatin for patients with advanced non-small cell lung
      cancer.
AB  - The survival of patients with advanced non-small cell lung cancer remains poor.
      Cisplatin-based chemotherapy produces a modest benefit in survival compared with
      that observed with best supportive care. Gemcitabine (Gemzar; Eli Lilly and
      Company, Indianapolis, IN), a novel nucleoside antimetabolite, is active and well
      tolerated. The combination of gemcitabine/cisplatin has shown a significant
      improvement in response rate and survival over cisplatin alone. Phase III trials
      comparing gemcitabine/cisplatin with older combinations such as
      cisplatin/etoposide or mitomycin/ifosfamide/cisplatin have shown a higher
      activity for gemcitabine/cisplatin; however, the best way to combine these drugs
      remains unclear. In addition, the 3-week schedule has obtained a higher dose
      intensity with less toxicity and similar efficacy as the 4-week schedule. The
      role of carboplatin in combination with new drugs is still under evaluation.
      Gemcitabine/carboplatin seems to be a good alternative, with the advantage of
      ambulatory administration and lower nonhematologic toxicity. The 4-week schedule
      has produced frequent grade 3/4 neutropenia and thrombocytopenia in some studies.
      The 3-week schedule, using gemcitabine on days 1 and 8 and carboplatin on day 1,
      is a convenient and well-tolerated regimen. The toxicity profile is acceptable
      without serious symptoms. This schedule could be considered a good option as a
      standard regimen. Semin Oncol 28 (suppl 10):4-9.

PMID- 11510028
TI  - A prospective study of gemcitabine and carboplatin as first-line therapy in
      advanced non-small cell lung cancer: toxicity of a three- versus a four-week
      schedule.
AB  - We evaluated the toxicity and activity of gemcitabine (Gemzar; Eli Lilly and
      Company, Indianapolis, IN) and carboplatin on a 3-week (trial A) versus a 4-week
      (trial B) schedule in patients with advanced/metastatic non-small cell lung
      cancer. Chemotherapy-naive patients in trial A received gemcitabine 1,000 mg/m(2)
      on days 1 and 8 plus carboplatin area under the curve of 5 on day 1, every 3
      weeks. In trial B, patients received gemcitabine 1,000 mg/m(2) on days 1, 8, and
      15 and carboplatin area under the curve of 6 on day 1, every 4 weeks. Thirty
      patients were enrolled in trial A and 28 in trial B. Patients received a total of
      142 cycles in trial A and 134 in trial B. Despite more frequent treatment delays
      (82 cycles in trial B and 20 cycles in trial A), and dose reductions/omissions
      (mainly on day 15), gemcitabine mean dose intensities of both schedules were
      similar. The principal dose-limiting toxicity was grade 3/4 thrombocytopenia.
      Objective response rates were 40% in trial A and 68% in trial B (no complete
      response). Gemcitabine and carboplatin administered on days 1 and 8 every 3 weeks
      is associated with lower myelotoxicity than that of a 4-week schedule, although
      both schedules were active against non-small cell lung cancer. Semin Oncol 28
      (suppl 10):10-14.

PMID- 11510029
TI  - Gemcitabine/carboplatin versus cisplatin/etoposide for patients with poor
      prognosis small cell lung cancer: a phase III randomized trial with quality-of
      life evaluation.
AB  - Small cell lung cancer is a chemosensitive disease; however, patients with
      extensive-stage disease or adverse prognostic factors are rarely cured.
      Gemcitabine (Gemzar; Eli Lilly and Company, Indianapolis, IN), a new agent with
      good tolerability, interacts synergistically with platinum agents. Carboplatin is
      as effective as cisplatin, but is less toxic. The London Lung Cancer Group is
      conducting a multicenter, open-label, randomized, phase III trial in patients
      with histologically or cytologically proven small cell lung cancer and extensive
      stage, limited-stage but locally-advanced, or limited-stage disease with poor
      prognostic factors. Chemotherapy consists of 21-day cycles of gemcitabine 1,200
      mg/m(2) intravenous (IV) on days 1 and 8, plus carboplatin area under the curve
      of 5 IV on day 1, or cisplatin 60 mg/m(2) IV on day 1 plus etoposide 120 mg/m(2)
      IV on day 1 and 100 mg orally on days 2 and 3. Thirty-nine patients have been
      randomized to gemcitabine/carboplatin and 38 to cisplatin/etoposide (23 and 22
      completed treatment, with 96 and 84 cycles, respectively). Preliminary toxicity
      data indicate hematologic toxicity in 25% of cycles for gemcitabine/carboplatin
      and 16% for cisplatin/etoposide, although cisplatin/etoposide-treated patients
      experienced significant alopecia, nephrotoxicity, nausea and vomiting, and
      neutropenia. This London Lung Cancer Group trial of gemcitabine/carboplatin may
      define an active, safe, and acceptable treatment for patients with extensive
      stage and poor-prognosis small cell lung cancer. Semin Oncol 28 (suppl 10):15-18.

PMID- 11510030
TI  - Gemcitabine/carboplatin in advanced urothelial cancer.
AB  - Transitional cell carcinoma of the urothelium is a highly chemosensitive tumor.
      Combination chemotherapy can provide both palliation and a modest survival
      advantage in patients with advanced disease. As shown in a recent phase III
      trial, the new gold standard should be considered gemcitabine/cisplatin, although
      toxicity remains important. Bladder cancer is a common tumor in our population
      (Spain), usually affecting elderly patients with comorbid diseases and renal
      impairment. Thus, most of these patients may not benefit from cisplatin-based
      regimens. The development of new combinations for treating such patients is,
      therefore, of vital importance. The identification of new active agents against
      transitional cell carcinoma, such as taxanes and gemcitabine, is promising. We
      believe that the combination of gemcitabine plus carboplatin could also be useful
      in this subset of patients. On this basis, we treated bladder cancer patients in
      two trials using gemcitabine 1,000 mg/m(2) on days 1 and 8, and carboplatin (area
      under the curve 5) on day 1, every 21 days. The overall response rate for
      evaluable patients with and without renal impairment was 60%, with a 95%
      confidence interval of 40% to 72%. The potential clinical benefit of this new
      doublet in the treatment of transitional cell carcinoma warrants testing in
      future phase III studies. Semin Oncol 28 (suppl 10):19-24.

PMID- 11510031
TI  - Combining gemcitabine with radiation in pancreatic cancer: understanding
      important variables influencing the therapeutic index.
AB  - We compared and evaluated available laboratory and clinical data on the use of
      concurrent gemcitabine (Gemzar; Eli Lilly and Company, Indianapolis, IN) and
      radiation in pancreatic cancer to provide guidance for subsequent prospective
      research initiatives. Preclinical data suggest that the timing of administration
      of gemcitabine with respect to radiotherapy is important, but this issue has not
      yet been confirmed by clinical data. Phase I clinical data indicate that the
      amount of acute toxicity from the combination of gemcitabine and radiotherapy is
      strongly related to the dose and schedule of administration of gemcitabine, as
      well as to the radiation field size. There also appears to be an inverse linear
      relationship between the maximum tolerated gemcitabine dose and radiation dose.
      Also important, but less clear, is the infusion rate of gemcitabine as it relates
      to the systemic efficacy of the drug. The combination of additional agents with
      gemcitabine and radiation appears to be feasible. Finally, the addition of
      radioprotectors may enable chemotherapy dose escalation, but safe escalation of
      the radiotherapy dose with newer techniques has not been established. Semin Oncol
      28 (suppl 10):25-33.

PMID- 11510032
TI  - Beyond pancreatic cancer: irinotecan and gemcitabine in solid tumors and
      hematologic malignancies.
AB  - Non-platinum combinations including gemcitabine and irinotecan (Gemzar; Eli Lilly
      and Company, Indianapolis, IN) for the management of a variety of malignancies
      have started to emerge. Gemcitabine and irinotecan are well-tolerated single
      agents, each with a broad spectrum of antitumor activity. Preclinical data
      suggests synergy for the two drugs when used in combination. A phase I trial has
      defined a well-tolerated combination regimen using both drugs on a day-1, -8
      schedule every 3 weeks. Phase II data suggest activity for the combination in
      pancreatic cancer, and a phase III trial of the two-drug combination versus
      gemcitabine alone is underway in previously untreated pancreatic cancer patients.
      Other phase II trials evaluating the impact of this combination on a variety of
      other tumors, such as non-small cell lung, small cell lung, breast, colorectal,
      and non-Hodgkin's lymphoma, are either forthcoming or in progress. Semin Oncol 28
      (suppl 10):34-43.

PMID- 11510033
TI  - Phase II study of gemcitabine, 5-fluorouracil, and leucovorin in patients with
      pancreatic cancer.
AB  - The primary goal of this phase II study was to determine the efficacy of
      gemcitabine (Gemzar; Eli Lilly and Company, Indianapolis, IN) plus 5-fluorouracil
      in patients with pancreatic cancer. Eligibility criteria included nonresectable
      locally advanced or metastatic pancreatic adenocarcinoma and measurable disease.
      Gemcitabine at 1,000 mg/m(2) and leucovorin at 20 mg/m(2) were administered
      intravenously 30 minutes before 5-fluorouracil 600 mg/m(2), weekly for 3 of every
      4 weeks. Twenty nine patients were enrolled. The overall response rate was 21%
      (95% confidence interval: 8% to 40%), consisting of one complete response and
      five partial responses; 16 patients (55%) had stable disease. Median survival was
      8.4 months (95% confidence interval: 2.6 to 14.2), and actuarial 1-year survival
      was 36%. Neutropenia (grade 3 only) was reported in 3.4% of patients, but was
      generally of short duration. No thrombocytopenia or evidence of cumulative
      myelosuppression was observed. The only significant nonhematologic events were
      grade 3 diarrhea and alopecia (both 3.4%). Gemcitabine plus 5-fluorouracil is
      active and well tolerated compared with results reported for each of these single
      agents. Thus, this combination justifies future comparative clinical trials.
      Semin Oncol 28 (suppl 10):44-49.

PMID- 11510034
TI  - Gemcitabine/cyclophosphamide/5-fluorouracil/folinic acid triplet combination in
      anthracycline- and taxane-refractory breast cancer patients: a Southern Italy
      Cooperative Oncology Group phase I/II study.
AB  - We sought to define the recommended dose of cyclophosphamide (CTX) for subsequent
      phase II assessment when combined with fixed doses of gemcitabine (Gemzar; Eli
      Lilly and Company, Indianapolis, IN) and 5-fluorouracil/folinic acid in
      metastatic breast cancer patients previously treated with anthracyclines and
      taxanes. Patients age 70 or less, with an Eastern Cooperative Oncology Group
      performance status 0 to 2, were enrolled. Patients received gemcitabine 1,000
      mg/m(2), 5-fluorouracil 425 mg/m(2), folinic acid 100 mg/m(2), and escalating
      doses of CTX (in 100-mg/m(2) increments), starting at 500 mg/m(2), on days 1 and
      8 every 3 weeks. Since March 1999, 46 patients, with a median age of 51 years
      (range, 38 to 74 years), entered the trial in seven cohorts. Cyclophosphamide
      dose escalation was stopped at 600 mg/m(2) when three of six patients experienced
      dose-limiting toxicity (one each with grade 3 thrombocytopenia, grade 3
      neutropenia, and persistent grade 2 neutropenia), and then continued with
      granulocyte colony-stimulating factor support. The CTX dose of 800 mg/m(2) was
      proven safe and was chosen for phase II study. Two complete and 15 partial
      responses provided an overall response rate of 37% (95% confidence interval, 23%
      to 51%). Gemcitabine/CTX/5-fluorouracil/folinic acid is well tolerated by
      metastatic breast cancer patients pretreated with anthracyclines/taxanes, up to a
      CTX dose of 800 mg/m(2). The phase II study is ongoing. Semin Oncol 28 (suppl
      10):50-56.

PMID- 11510035
TI  - A phase II study of neoadjuvant gemcitabine plus doxorubicin in stage IIIB breast
      cancer: a preliminary report.
AB  - The purpose of this ongoing study is to determine the response and safety of a
      combination of gemcitabine (Gemzar; Eli Lilly and Company, Indianapolis, IN) plus
      doxorubicin as neoadjuvant therapy for stage IIIB breast cancer. Thirty-nine
      chemotherapy-naive patients were enrolled in the study. The median age was 54
      years (range, 32 to 74 years), and the median Karnofsky performance status was
      100. Gemcitabine 1,200 mg/m(2) was given on days 1 and 8, and doxorubicin 60
      mg/m(2) on day 1, followed by surgery or radiotherapy. Ninety-seven of 117 cycles
      (83%) were administered at full dose. An overall response rate of 95% was
      obtained, with a complete response in 18% (seven patients) and a partial response
      in 77% (30 patients). Twenty-eight patients (72%) underwent breast surgery after
      a maximum of three cycles of neoadjuvant therapy. World Health Organization grade
      3/4 toxicities included leukopenia in nine cycles (8%), neutropenia in 16 cycles
      (14%), febrile neutropenia in 11 cycles (9%), and anemia in two cycles (2%). The
      most important nonhematologic toxicity was grade 2/4 mucositis in 16 cycles
      (14%), and/or grade 2/3 diarrhea in 10 cycles (9%). Neoadjuvant therapy with
      gemcitabine plus doxorubicin results in a high tumor response rate with moderate
      oral and hematologic toxicity. Semin Oncol 28 (suppl 10):57-61.

PMID- 11510036
TI  - Gemcitabine in ovarian cancer.
AB  - Newer agents and combinations are needed in order to improve current results in
      the treatment of ovarian cancer. Gemcitabine (Gemzar; Eli Lilly and Company,
      Indianapolis, IN) is a novel agent with a unique mechanism of action that has
      shown consistent activity as a single-agent in platinum-resistant ovarian cancer,
      with remission rates of nearly 20% and a favorable toxicity profile. Because of
      these benefits and its shown clinical and preclinical synergism with platinum
      analogues, gemcitabine has been combined with carboplatin as a rational approach
      for the treatment of ovarian cancer patients. The combination has been studied in
      phase I and II trials aimed at determining the optimal schedule and potential
      activity. Triplets including paclitaxel are also feasible. Further combinations
      of gemcitabine and other agents are being actively studied in both treated and
      untreated patients with ovarian cancer in order to establish its role in the
      management of this disease. Semin Oncol 28 (suppl 10):62-69.

PMID- 11510037
TI  - [Surgical treatment of glomus tumors in the middle ear].
AB  - Twelve 42-63 year-old women were treated surgically for glomal tumors of the
      middle ear. The operation implied removal of the posterior wall of the external
      acoustic meatus along the canal of the facial nerve. This provided creation of a
      wide cavity and approach directly to the base of the tumor. In glomal tumors of
      the middle ear surgical treatment is a method of choice. The proposed surgical
      approach is thought optimal for removal of middle ear chemodectoma.

PMID- 11510038
TI  - [Mechanisms of onset and signs of latent mastoiditis in patients with exudative
      otitis media].
AB  - Tympanomastoidotomy was performed in 42 patients with exudative otitis media
      running from 4 to 8 weeks. Large size of the antral cells and high pneumatization
      of the translabyrinthine tract cells contribute to the onset of latent antritis;
      large size of the apical cells and hyperpneumatization of the cells of the
      inferior labyrinthine tract predispose to emergence of isolated apical
      mastoiditis in patients with exudative otitis media at early stages. Latent
      mastoiditis and mucoperiostitis in the region of perifacial and perilabyrinthine
      cells in patients with exudative otitis media are evidenced by early atypical
      cochleovestibular complaints, mixed hypoacusis and variability of tympanograms.

PMID- 11510039
TI  - [Pathogenesis and treatment of chronic purulent otitis media and its
      complications: immunological aspects].
AB  - Clinicoimmunological, microbiological and cytological examinations were made in
      96 patients with otitis media purulenta chronica (OMPC) and otogenic intracranial
      complications. It was found that in different clinical forms of OMPC nonspecific
      defense and immunity indices vary. In OMPC and chronic purulent mesotympanitis
      the indices change insignificantly. In chronic purulent epitympanitis and
      otogenic intracranial complications there was suppression in T-cell immunity and
      nonspecific defense. Middle ear secretion contained less SIgA and lysozyme, blood
      contained more amount of IgA and IgM and less of IgG. Deficiency of general and
      local defense antiinfectious mechanisms shows significance of immune and
      nonspecific resistance in transformation of ear inflammation into chronic phase
      and development of complications. Alterations in immunity, nonspecific defense
      and tympanic cavity depend on the causative agent of OMPC. Association of St.
      aureus with gramnegative flora or anaerobic infection cause the greatest immune
      deficiency. Temporal bone surgery and standard treatment for 21 days fail to
      eradicate initial immune disorders in the blood and middle ear. Thymalin
      immunocorrection improves nonspecific defense and immunity, attenuates
      inflammation and stimulates reparative processes in the trepanation wound of the
      ear.

PMID- 11510040
TI  - [Choice of rehabilitation in patients with mixed hypoacusis].
AB  - The article presents classification of mixed forms of hypoacusis based on certain
      combination of audiological criteria reflecting the impact of a hypoacusis
      neurosensory component. A differential approach to rehabilitation of patients
      with mixed hypoacusis caused by chronic pathological processes in the middle ear
      is proposed. The approach allows for severity of neurosensory hearing disorders.

PMID- 11510041
TI  - [Early detection of a sensorineural aspect of hypoacusis in patients with chronic
      purulent otitis media].
AB  - To detect initial signs of internal ear dysfunction in 87 patients with otitis
      media purulenta chronica (OMPC), wide-rage frequency audiometry (WRFA) in bone
      and air conduction according to B.M. Sagalovich was used. Most of the patients
      with normal bone conduction in frequencies up to 8 kHz had higher bone thresholds
      in wide-range frequencies. In mixed hypoacusis these thresholds rose to the
      highest degree. A correlation was found between a rise of auditory thresholds
      wide range of frequencies in bone conduction and the disease duration.

PMID- 11510042
TI  - [Parameters of high-frequency audiometry in patients with vocal defects, vascular
      diseases or exposed to noise, radiation].
AB  - High-frequency audiometry was performed in 100 patients with vascular diseases,
      vocal defects, exposed to noise or radiation. In normal hearing these patients
      had in normal frequency range elevated auditory thresholds for higher-frequency
      tones. The strongest abnormalities were registered in patients with vocal
      problems and Chernobyl wreckers. Examination of hearing in wide range of
      frequencies in patients with vocal problems can detect subclinical hearing
      defects and help in assessment of vocal defects severity and in issues of
      occupational expertise.

PMID- 11510043
TI  - [Characteristics of respiratory pattern, voice production and conduction in
      persons of vocal professions].
AB  - The authors studied external respiration, voice production and voice conduction
      in teachers. Occupation-specific compensatory features are described.

PMID- 11510044
TI  - [Photodynamic therapy of recurrent and residual oropharyngeal and laryngeal
      tumors].
AB  - Photodynamic therapy (PDT) was given to 61 patients with recurrent cancer of the
      tongue, oral mucosa, lower lip, oro- and nasopharynx, larynx. Photosensitizers
      photogem and photosens of Russian produce were employed. The radiation was given
      twice with the interval 24 and 48 hours, the exposure to light 3 to 30 min. The
      impact was external, through the instrumental canal of the fibroscope, by
      intracavitary and interstitial techniques. The response was assessed within 4-6
      weeks after the PDT course. The effect was observed in 95.1% patients. Its
      duration ranged from 4 months to 5 years. Complete resorption of the tumor was
      achieved in 57.4%. The treatment failed in 4.9% patients.

PMID- 11510045
TI  - [Surgical treatment of Meniere's disease and its pathophysiological validation].
AB  - The authors analyse their own and literature data on surgical treatment of
      Meniere's disease (MD) as intervention on the endolymphatic sac with assessment
      of various modifications by long-term results, on sympathetic intraaural and
      extraaural lesions. Surgical interventions on the endolymphatic sac are
      pathophysiologically validated. Insufficient knowledge on hydrodynamics in the
      internal ear labyrinth and the role of endolymphatic hydrops in MD pathogenesis
      hampers assessment and further development of surgical treatment of the disease.
      Future lines of the research in Meniere's disease and its treatment are outlined.

PMID- 11510046
TI  - [Cause-effect relationship in combination of purulent intracranial processes with
      ENT diseases].
AB  - 36 case histories were analyzed. The patients had purulent intracranial processes
      combined with inflammation of the paranasal sinuses and ear. Cause-effect
      relationships in development of the above diseases are considered. It was found
      that paranasal and auricular inflammation combined with purulent intracranial
      processes do not cause always the latter. The ENT diseases may develop not only
      in parallel with purulent intracranial pathology, but also as its complication.
      It is shown that post-mortem hyperdiagnosis exists of ethmoidal and sphenoid
      inflammation as a cause of purulent intracranial processes.

PMID- 11510047
TI  - [Postintubation laryngeal and tracheal stenosis: diagnosis and treatment].
AB  - The authors present 10-year experience gained in the treatment of 450 patients
      subjected to intubation, artificial lung ventilation, tracheostomy in critical
      care units. Updated approaches to the diagnosis, treatment and prevention in the
      above patients, classification of postintubation stenoses of the larynx and
      trachea allowed to raise rehabilitation effectiveness to 95 and 78% in patients
      with early (within 3 months after intubation) and late (more than 3 months after
      intubation) stenosis, respectively.

PMID- 11510048
TI  - [Prognosis and criteria of recovered motility of one of the vocal cords in the
      middle position as a result cordectomy].
AB  - Complex assessment of changes in laryngoscopic picture, direct laryngoscopy under
      anesthesia, tomography, thermography of the larynx and electrodiagnosis allows
      prognosis of recovery of motility of one of the vocal cords. The reflex spasm was
      relieved with corporal reflex therapy and novocain blockade of Zakharyin-Ged
      zones for the larynx. Out of 26 patients 11 recovered motility of the vocal cord
      due to the novocain blockades, 4--due to the corporal reflex therapy and 4
      patients--spontaneously. No response was achieved in 7 patients.

PMID- 11510049
TI  - [Causes of lethal outcomes in croup syndrome in children].
AB  - The paper reports 40 cases of lethal outcomes in children with croup syndrome
      treated in Morozov Children's Moscow City Hospital in 1985-1998. 92.5% of them
      died of severe pneumonia complications, 7.5%--of sepsis. 70% of the deceased were
      infants aged 0-2 years, 75% of them were boys. All the children had aggravated
      premorbid background. The sputum and organ tissues contained in most cases
      association of viruses with staphylococci and streptococci resistant to standard
      antibiotics (penicillin, ampicillin, cefazoline). The conclusion is made that
      children with croup died primarily of severe pneumonia complications in low
      systemic reactivity and bacterial-viral association of the agents resistant to
      the antibacterial therapy.

PMID- 11510050
TI  - [Electrostimulation of laryngeal muscles with fluctuating currents in the
      treatment of patients with unilateral laryngeal paralysis].
AB  - Intralaryngeal electrostimulation of the laryngeal muscles with fluctuating
      currents with simultaneous mobilization of the arytenoid cartilage and paralysed
      vocal cord were used in 42 patients with unilateral laryngeal paralysis. The
      treatment was combined with phonopedic lessons. The control group consisted of 32
      patients receiving standard electrostimulation with diadynamic currents. The
      effect was evaluated by changes in vocal acoustic parameters and stroboscopic
      parameters. In patients with paramedian fixation of the vocal cords voice
      improvement was obtained irrespective of electrostimulation type. For patients
      with intermedian and lateral fixation of the vocal cords more effective was
      intralaryngeal electrostimulation with fluctuating currents. A good therapeutic
      effect was achieved in patients with dislocation of the arytenoid cartilage.

PMID- 11510051
TI  - [Treatment policy in thrombophlebitis lesions of the sigmoid sinus and internal
      jugular vein during intensive use of antibiotics].
AB  - 152 patients were admitted to the ENT hospital with the diagnosis
      thrombophlebitis of the sygmoid sinus (62.1% of the total number of the admitted
      patients with otogenic intracranial complications). The surgery was made early
      upon the admission. The authors advocate radical removal of the thrombus before,
      the start of hemorrhage from both sinus parts. In case of the absence of low
      hemorrhage the intervention on the internal jugular vein was decided on day 1-3
      after the basic surgery depending on the clinical course. It is thought that in
      postoperative period antibiotic therapy should be supplemented with immune
      preparations made of donor blood, UV radiation of autoblood and hyperbaric
      oxygenation.

PMID- 11510052
TI  - [Tympanoplasty for patients with destruction of the stapes].
AB  - Mode of tympanoplasty allowing reconstruction of the drum and erosioned malleus
      handle is described. For this purpose an autoossicle fragment of the lengthened
      shape was inserted into the blind channel created in fascia transplant which
      "dressed" on the handle's remnant for the osseous fragment and remnants of the
      handle to appear in one fascia channel. This method was applied in 11 patients
      with subtotal drum perforation and erosion of the hammer's handle. In 9 of them
      0.5-2 years later the defect of the drum fully disappeared. In 7 patients the
      handle resumed normal length while the drum became conic. The average pure air
      conduction threshold in frequencies 0.5-2 kHz has become 25.5 +/- 3.5 dB (before
      the operation 38.2 +/- 2.3 dB; p > 0.01), the average bone conduction threshold
      14.3 +/- 2.6 dB (before operation 13.9 +/- 2.4 dB; p < 0.05).

PMID- 11510053
TI  - [Betaserk efficiency in cochlear and vestibular disorders in the regional
      surdocenter].
AB  - The results are available of the outpatient treatment of 10 patients with
      cochlear and vestibular disorders with the drug betaserk. The previous treatment
      was ineffective. Surdological indications for betaserk are described.

PMID- 11510054
TI  - [Effectiveness of Imudon in patients with acute and chronic inflammatory diseases
      of pharynx].

PMID- 11510055
TI  - [The application of IRS-19 in otorhinolaryngology].

PMID- 11510056
TI  - [A giant fibroma of the oropharynx in a 4 -year-old child].

PMID- 11510057
TI  - [An unusual foreign body in the esophagus].

PMID- 11510058
TI  - [Therapeutic and diagnostic policy in patients with bilateral vestibular
      schwannoma].

PMID- 11510059
TI  - [The condition of the middle ear mucosa in chemodectoma of the tympanic glomus at
      the early stage of the disease].
AB  - 28 samples of tissue from the middle ear obtained at removal of chemodectoma were
      studied histologically. Investigation of the tympanic cavity mucosa has shown
      correlation between the severity of fibroatrophic changes in the middle ear
      mucosa and duration of the disease. Pathomorphological alterations in the middle
      ear mucosa at early stages of chemodectoma (stage I and II) are similar to those
      in chronic lingering mucositis.

PMID- 11510060
TI  - [Blood concentration of propofol during cardiopulmonary bypass--comparison
      between arterial and internal jugular venous blood].
AB  - Twelve adult patients for cardiac surgery were divided into 2 groups,
      normothermia (6 patients) and mild hypothermia (6 patients), based on their body
      temperature during cardiopulmonary bypass (CPB). Propofol was continuously
      administered throughout each operation at a dose of 2 mg.kg-1.h-1. Arterial and
      internal jugular venous bulb blood samples were drawn simultaneously before CPB,
      at 5, 30, 60, and 90 minutes after the start of CPB, 30 minutes after the end of
      CPB, and at the conclusion of the operation, to measure propofol concentrations.
      In the normothermia group, propofol concentration in the arterial blood decreased
      significantly 5 minutes after the start of CPB, and then recovered immediately to
      the pre-CPB value. In the mild hypothermia group, however, no significant change
      in propofol concentration was observed. In both groups, there was no significant
      difference in propofol concentration between arterial and internal jugular venous
      bulb blood throughout the study period. Our results suggest that there are no
      significant differences between the effect of normothermic and that of mild
      hypothermic CPB on the pharmacokinetics of propofol in the brain.

PMID- 11510061
TI  - [Evaluation of adhesive tape containing lidocaine using current perception
      threshold measurement].
AB  - Lidocaine adhesive tape (Penles; Wyeth Lederle Japan, Ltd, Tokyo, Japan) is
      placed for pain relief prior to puncturing a vein with a needle. We investigated
      the optimal time interval from application of Penles to vein puncture by
      measuring current perception threshold (CPT) levels with a Neurometer, by which
      it was possible to measure the extent of nerve block in a non-invasive and
      quantitative manner with 3 electrical stimulus rates (2000 Hz, 250 Hz, and 5 Hz).
      Penles was applied to the dorsum of volunteers' hands for 1, 2, 4, 6 and 12 hours
      before measuring CPT levels. With a stimulation rate of 2000 Hz and 250 Hz, CPT,
      levels were found to increase 4 hours after the Penles application, while peak
      CPT levels for 5 Hz stimulation were observed from 6 to 12 hours after
      application. However, CPT levels tended to decrease 12 hours after application,
      regardless of the stimulus rate. From the result, we conclude that Penles
      provides maximum benefit when applied 6 hours prior to vein puncture.

PMID- 11510062
TI  - [The effect of intravenous patient controlled analgesia on activities of daily
      life and medical expense after thoracotomy].
AB  - We investigated the efficacy of postoperative intravenous patient controlled
      analgesia (i.v.-PCA) combined with continuous epidural analgesia (CEA) after
      thoracotomy. One hundred and eight patients receiving postoperative CEA were
      randomly divided into two groups; the i.v.-PCA (+) group who received i.v.-PCA
      combined with CEA and the i.v.-PCA (-) group who did not receive i.v.-PCA. Pain
      score (100 mm visual analogue scale; VAS) at 24 h and 48 h, postoperative
      complications, activities of daily life (ADL), the length of hospital stay and
      medical expense were compared. The length of hospital stay and medical expense
      were not significantly different between the two groups. The i.v.-PCA (+) group
      could recover ADL more quickly and had better analgesic state compared with the
      i.v.-PCA (-) group. The incidence of postoperative complications was lower in the
      i.v.-PCA (+) group compared with the i.v.-PCA (-) group. It was concluded that
      the i.v.-PCA combined with CEA had the desirable effects on postoperative
      analgesia and recovery of postoperative ADL.

PMID- 11510063
TI  - [Patient-controlled epidural analgesia with bupivacaine and fentanyl suppresses
      postoperative delirium following hepatectomy].
AB  - Postoperative delirium occurs frequently following major surgery, especially
      after hepatectomy. We hypothesized that better methods of postoperative pain
      control would decrease postoperative delirium. To clarify the magnitude of
      postoperative pain and incidence of postoperative delirium in hepatectomy
      patients, subjects received patient-controlled epidural analgesia (PCEA) using
      bupivacaine and fentanyl (Group P), or continuous epidural mepivacaine (Group E)
      following intraoperative epidural administration of morphine. The magnitude of
      postoperative pain was estimated by use of an analgesic adjuvant and delirium was
      classified as mild (insomnia, disturbance of sleepwake cycle), moderate
      (disorientation, hallucination), or severe (restlessness, confusion, agitation),
      based on the medical records. Analgesic adjuvant usage was less in Group P than
      in Group E, while the incidences of moderate and severe delirium were
      significantly less frequent in Group P than in Group E (35.7% versus 75.0%, and
      14.3% versus 50.0% respectively). Moreover, less amount of antipsychotic drugs
      was given in Group P than in Group E. These results suggest that the better pain
      relief and patient satisfaction provided by PCEA contributed to a decrease in the
      incidence of delirium, because of continuous opioid administration and patient
      control analgesia. We concluded that PCEA with bupivacaine and fentanyl can limit
      postoperative delirium following hepatectomy.

PMID- 11510064
TI  - [The effect of sedation with propofol and fentanyl during epidural catheter
      insertion on intraoperative temperatures].
AB  - General anesthesia inhibits thermoregulation by suppressing tonic
      vasoconstriction and facilitates a core-to-peripheral redistribution of body
      heat, which is the major cause of core hypothermia during the first hour of
      anesthesia. We randomly assigned 16 patients to two groups; 1) patients who
      received fentanyl (1 microgram.kg-1, i.v.) and propofol (1.5 mg.kg-1.h-1) during
      insertion of epidural catheters (P group), and 2) no drug (control) group (C
      group). We measured tympanic (Ttym) and skin temperatures at the time of
      admission to operating rooms, after dural catheter insertion, before induction of
      anesthesia, just after induction of anesthesia, and one hour after induction.
      After dural catheter insertion, forearm-finger tip skin temperature gradient of P
      group was significantly smaller than C group. One hour after induction of
      anesthesia, Ttym of P group was significantly higher than C group. We can
      conclude that a sedative dose of propofol and fentanyl before induction of
      general anesthesia inhibits redistribution hypothermia during general anesthesia.

PMID- 11510065
TI  - [Perioperative assessment of blood lactate levels in pediatric heart surgery].
AB  - Measuring arterial lactate concentration is a prompt, easy and relatively non
      invasive way to estimate tissue oxygen metabolism. We evaluated whether
      perioperative levels of the arterial lactate concentrations can reflect the
      general severity of a pediatric patient's condition. A consecutive series of 112
      patients, aged 5 days to 17 years (median age: 12 months), admitted to our
      pediatric intensive care unit (PICU) following cardiac surgery under
      cardiopulmonary bypass were studied. Arterial blood lactate concentration was
      measured preoperatively, immediately upon termination of the cardiopulmonary
      bypass (postCPB), immediately following the operation, and 16th hours
      postoperatively (D1). Trends within arterial lactate concentrations were examined
      in relation to mortality rates, the duration of PICU stays and the patient's
      ages. The studied population had a mortality rate of 5.7% (6 patients). Lactate
      levels increased significantly and exceeded 4.0 mmol.l-1 during postCPB
      measurements in a majority of the patients. The increases in lactate levels are
      affected by the changes in interorgan blood flow, blood glucose levels and/or
      blood pH in addition to the effects of the CPB-priming lactated Ringer's
      solution. Thus, higher cut off values have to be determined, and lower
      probabilities assigned, when using postCPB lactate levels to predict the severity
      of an outcome. Significantly and sustained increases in D1 lactate levels were
      noted in neonates, patients with longer PICU stays (> 15 days) and those died
      later. Hyperlactemia greater than 2.2 mmol.l-1 at D1 predicted death with a
      sensitivity of 82% and a specificity of 72%. The measurement of early
      postoperative lactate levels, reflecting postoperative ability to eliminate
      intraoperative hyperlactemia, is a better way of assessing the severity of a
      pediatric patient's condition following cardiac surgery. The ideal time to
      measure early postoperative lactate levels should be determined by further
      research.

PMID- 11510066
TI  - [Intraoperative assessment of cardiac function with transesophageal
      echocardiography during the Batista operation].
AB  - We experienced anesthetic management for six cases of the Batista operation and
      measured cardiac function before and after cardiopulmonary bypass (CPB) with
      transesophageal echocardiography. In the successful three patients, left
      ventricle ejection fraction and ejection time were maintained over 25% and 200
      msec after CPB, respectively. In the other three resulting in implantation of
      left ventricular assist device, ejection fraction remained below 20% and ejection
      time under 200 msec after CPB. Intraoperative transesophageal echocardiography
      may be useful not only for monitoring of cardiac function but also for the
      prediction of prognosis.

PMID- 11510067
TI  - [The spread and time to two-segment regression of spinal anesthesia with 0.25%
      hyperbaric bupivacaine].
AB  - The spread and time to two-segment regression of spinal anesthesia with 0.25%
      hyperbaric bupivacaine 2.0 ml (5 mg) were studied clinically in 20 patients for
      elective lower extremity, urological or gynecological surgery. Lumbar puncture
      was performed at the L 3-4 interspace with the patient in horizontal lateral
      decubitus positions using a 25-G Quincke needle. After injection of the local
      anesthetic solution at the rate of 0.2 ml.sec-1, the patient was placed
      immediately in supine position. Sensory block was assessed by using pinprick and
      motor block was assessed by using a four-point Bromage scale in every 5 min until
      30 min, then every 10 min thereafter until two-segment regression of sensory
      block had recovered. Results were expressed as mean values +/- SD. Maximum
      sensory block level was Th 10.6 +/- 2.3, and time to two-segment regression was
      51.5 +/- 14.6 min. Complete motor block was observed in three out of twenty
      patients (15%). These results indicate that spinal anesthesia with 0.25%
      hyperbaric bupivacaine is useful for a short case, which dose not require motor
      block or is performed as day-care surgery.

PMID- 11510068
TI  - [Radiological assessment of the structural relationship between the trachea and
      the innominate artery in physically disabled and scoliotic children].
AB  - Studies were made on the physically disabled and scoliotic children who underwent
      tracheostomy. The purpose was to clarify factors that might lead to the tracheo
      innominate artery fistula, by use of three-dimensional helical CT (3 DCT). In a
      case of right scoliosis, the tracheo-innominate artery fistula may be caused by
      the left-ward displacement of the trachea from the vertebra, having the
      innominate artery ride over the trachea and compressing it. In a case of the
      physically disabled and scoliotic children, there may be more compression on the
      trachea by the innominate artery along with the worsening scoliosis. Therefore,
      we consider it necessary to examine the structural relationship between the
      trachea, the vertebra, and the innominate artery periodically by 3 DCT.

PMID- 11510069
TI  - [Stump pain relieved by continuous intravenous ketamine infusion therapy].
AB  - We experienced a case of stump pain relieved by continuous intravenous ketamine
      infusion therapy. A 59-year-old male had his left first through fourth toes
      amputated because a giant iron plate at work fell on his left foot fifteen years
      ago. Thereafter he had refractory spontaneous burning pain and night pain on his
      stump. On examination, we found his left foot skin hard, lustrous, and with
      sweating disturbance, allodynia and hyperpathia. As intravenous administrations
      of ketamine 10 mg and thiamylal 50 mg were positive as a drug challenge test, we
      performed intravenous ketamine infusion at 1 mg.kg-1.hr-1 for 1 hour and a half.
      After this treatment, his visual analogue scale (VAS) improved dramatically to 0
      mm, and night pain, allodynia and hyperpathia disappeared for three days.
      Thereafter stump pain was relieved to the level of VAS 20 mm. Therefore we
      diagnosed his stump pain as central pain of neuropathic origin. We suspect that
      continuous intravenous infusion of ketamine, a noncompetitive blocker of N-methyl
      D-aspartic acid receptor, might be an effective and useful alternative treatment
      in a patient with refractory stump pain.

PMID- 11510070
TI  - [Perioperative management of a neonate with aglossia-adactylia syndrome].
AB  - Aglossia-adactylia syndrome is a rare disorder characterized by aglossia and
      deformity of the limbs of variable degree. We managed a 2-day-old neonate with
      ileojejunal atresia with aglossia-adactylia syndrome. He was scheduled for the
      repair of the intestinal atresia, gastrostomy and palatal impression taking,
      under general anesthesia with sevoflurane supplemented with fentanyl. In this
      case we could achieve tracheal intubation by direct laryngoscopy with cricoid
      pressure applied, and could manage without any complications. But many of the
      patients with this syndrome are complicated with cleft palate and micrognathia,
      and we should be careful of the difficult airway at the induction of general
      anesthesia and aspiration during perioperative period.

PMID- 11510071
TI  - [Difficult ventilation during induction of anesthesia in a patient with Arnold
      Chiari malformation type II].
AB  - Arnold-Chiari malformation is a congenital disorder with caudal displacement of
      the cerebellar tonsils through the foramen magnum into the cervical canal. We
      report difficulty with ventilation during the induction of anesthesia due to
      apnea and laryngospasm in a 5-year-old female with Arnold-Chiari malformation
      type II diagnosed at birth. She had had short periods of apnea during infancy,
      but was asymptomatic recently. Slow induction of anesthesia was performed using
      sevoflurane, but just after induction, the patient developed apnea and we could
      not ventilate her due to laryngospasm. We woke her up, and induced anesthesia
      with barbiturates. The operation was performed without complications, but she had
      another apnea attack with laryngospasm at extubation. This case suggests that it
      is important to be aware of the possibility of apnea due to disorder of the
      respiratory center in patients with Arnold-Chiari deformity.

PMID- 11510072
TI  - [Superimposed high-frequency jet ventilation induced deterioration of oxygenation
      during whole lung lavage in a patient with pulmonary alveolar proteinosis].
AB  - A 39-year-old man suffering from pulmonary alveolar proteinosis underwent whole
      lung lavage of the right lung under one-lung ventilation with total intravenous
      anesthesia in the right lateral position. Superimposed high-frequency jet
      ventilation (SHFJV) was applied for approximately 10 minutes during lung lavage.
      The settings of HFJV were as follows: FIO2 = 1.0, rate = 150 bpm, driving
      pressure = 1 atm, inspiratory time = 30% of cycle. Since peak inspiratory
      pressure was high (29 cm H2O) during intermittent positive pressure ventilation
      (IPPV) due to severe bridle ventilation impairment, HFJV was performed only in
      the exhalation phase of IPPV. SpO2 and PaO2 at the time of unilateral lung
      filling declined following initiation of SHFJV, from 98% and 93 mmHg to 95% and
      62 mmHg, respectively. Although pulmonary arterial pressure tended to be slightly
      elevated, little change in blood pressure, cardiac output and central venous
      pressure was observed. SpO2 was quickly restored after the end of SHFJV. The
      reason for deterioration of oxygenation might have been an increase in shunt due
      to shift of pulmonary blood flow from the ventilated lung to the nonventilated
      lung. These findings suggest that performance of SHFJV during lung lavage for a
      patient with advanced pulmonary alveolar proteinosis may cause pulmonary
      oxygenation capacity to deteriorate even when circulatory inhibition is minimal.

PMID- 11510073
TI  - [Perforation of the superior vena cava and hemothorax caused by insertion of a
      pulmonary artery catheter].
AB  - A 70-year-old woman with aortic regurgitation was scheduled for aortic valve
      replacement. After induction of anesthesia resistance was encountered when
      attempting to remove the guide wire with a sheath dilator prior to insertion of a
      pulmonary artery (PA) catheter through the right internal jugular vein. Ten hours
      after catheter insertion, chest X-ray examination in ICU showed poorly delineated
      right lung field, and hemothorax was suspected, as a large amount of fluid was
      also seen draining from the chest drain tube. Twenty two hours after catheter
      insertion, we opened her chest and found that the superior vena cava (SVC) had
      been perforated. After surgical closure of the hole on the SVC, the hemodynamics
      because stabilized and active bleeding was controlled. The patient was
      subsequently discharged from the hospital without any further complications. This
      perforation was thought to be caused by carelessness during insertion of the PA
      catheter. To prevent serious complications, such as perforation of the great
      vessels or heart by a catheter, the results of the present case suggest that
      careful attention is required during catheterization, especially when resistance
      is encountered.

PMID- 11510074
TI  - [Fiberoptic nasal intubation in a patient with huge laryngeal cyst].
AB  - Huge laryngeal cyst is rare, but may cause difficulty or inability in tracheal
      intubation during induction of general anesthesia. A 69-year-old patient was
      scheduled for laryngomicroscopic cystectomy. In this patient, we examined two
      methods of oro-tracheal intubation either with rigid laryngoscopy or flexible
      fiberscopy using transnasal fiberoptic monitoring. Direct laryngoscopy failed to
      expose the epiglottis because of large cyst being fragile and easy to bleed. And
      even oral fiberscopy intubation was also difficult since a large mass hindered
      acquiring a suitable view. However, trans-nasal fiberscopy monitoring could guide
      the oro-tracheal fiber into the trachea for intubation. When an anesthesiologist
      can predict the abnormality of epiglottis, this combination might be recommended
      for difficult airway and intubation. Postoperative respiratory management under
      intubating state was necessary because of bleeding, airway edema, and deviation
      of the larynx after tumor resection. We reported anesthetic management of a
      patient with epiglottis gigantic cyst occupying the laryngopharyngeal airway. It
      is a rare tumor leading to difficulty of induction of anesthesia and
      necessitating postoperative intubated respiratory care.

PMID- 11510075
TI  - [Anesthetic management of a child with congenital sensory neuropathy with
      anhydrosis].
AB  - Congenital sensory neuropathy with anhydrosis is a rare disorder characterized by
      insensitivity to pain with normal tactile perception, self-mutilation,
      anhydrosis, recurrent unexplained fever, mental retardation and variable
      autonomic abnormality. We managed a 14-year-old boy with this syndrome who
      underwent repair of right femur fracture. Anesthesia was induced with propofol
      and ketamine. Adequate depth of anesthesia was carefully controlled by processed
      electroencephalogram, and core body temperature was maintained at 37.0 degrees C
      during the surgery. The patient was well sedated, and nausea and vomiting were
      not noted postoperatively. Use of droperidol and propofol may be beneficial for
      anesthetic management of this syndrome, because droperidol exerts residual
      hypnotic effect postoperatively, and both drugs have antiemetic property.

PMID- 11510076
TI  - [On line display of the reconstructed pressure waves of the radial artery from
      the monitored output pressure waves at the same site].
AB  - The input-output relationship of transducer and catheter system is described by
      linear, second-order differential equation with three coefficients: inductance
      (L), resistance (R), and capacitance (C). Once the natural frequency (fo) and the
      damping ratio (beta) of the monitoring system have been measured, three
      coefficients of the differential equation are uniquely obtained. We measured the
      frequency response of the monitoring system, which we usually use in our
      hospital, to obtain fo and beta, and reconstructed the original input arterial
      pressure wave from output signal on the display using the simple time-domain
      approach. The analysis of this linear, second-order differential equation, is
      applicable in on-line bedside monitoring, because the calculation of this
      equation is simpler than that using Fourier's translation. The pressure waves of
      the radial artery both monitored (output) and restored (input) were depicted on
      the same display at the same time. We can evaluate the changes in systemic
      circulation from the changes in the wave shapes of arterial blood pressure.

PMID- 11510077
TI  - [Introduction and clinical evaluation of a new non-invasive cardiac output
      monitor (NICO) based on Fick partial CO2 rebreathing method].
AB  - A newly developed non-invasive monitor, NICO (Novametrix Medical Systems Inc.),
      measures cardiac output based on changes in respiratory CO2 concentration caused
      by a brief period of rebreathing. By applying modified form of the CO2 Fick
      principle, cardiac output is calculated. We determined the accuracy and precision
      of this technique (RBCO) by comparing it with continuous thermodilution technique
      (TDCCO) and pulse dye densitometry technique (PDD). The overall difference
      between RBCO and TDCCO(n = 46) was -0.21 +/- 1.43 (bias +/- 2 SD)l.min-1. On the
      other hand, the overall difference between RBCO and PDD (n = 53) was -0.1 +/-
      2.04 (bias +/- 2 SD)l.min-1. The degree of accuracy of RBCO was thought to be the
      same as those of TDCCO and PDD. We expect that NICO will be a useful cardiac
      output monitor in any method of general anesthesia in which PA catheterization is
      difficult or not indicated.

PMID- 11510078
TI  - [The situation of anesthesia in Afghanistan].
AB  - As a medical co-ordinator of the International Red Cross, I surveyed the
      situation of the anesthesia in the major hospitals in Afghanistan. There was
      almost no hospital to be able to carry out elective surgery except emergency
      operation, and even the basic facilities for anesthesia were not available in
      these hospitals. The improvement of country's health situation depends mainly on
      country's economical progress, besides foreign aid. Although the medical aid for
      these conflict areas is strongly requested to Japan as international
      contribution, a conflict itself destroys the social infra-structure of war torn
      countries, and therefore such medical aid is not easily accomplished.

PMID- 11510079
TI  - [Psychopathology and outcome in first-admission schizophrenia: a 13-year follow
      up study at a medical school hospital].
AB  - BACKGROUND: The course and outcome of 'dementia praecox' have attracted
      considerable attention since it was first described. However, studies in which
      schizophrenic patients have been followed for more than ten years are rare. In
      this study, the course and outcome of first-admission schizophrenic patients in
      Jichi Medical School Hospital was investigated. METHOD: The subjects were 62
      schizophrenic patients, 29 females and 33 males (the mean age at first
      hospitalization was 25.2 +/- 7.4 years), who were consecutively discharged from
      the Department of Psychiatry, Jichi Medical School Hospital, between June 1983
      and May 1988. The mean interval between first-admission and follow-up was
      thirteen years. The social outcome was measured using Eguma's Social Adjustment
      Scale. The subjects were divided into two groups according to Eguma's Scale: a
      favorable outcome group and an unfavorable outcome group. The following data were
      obtained from clinical records and analyzed: sex, family history of mental
      disorders, educational background, job experience, marital status, age at first
      contact to a psychiatrist, age at first hospitalization, type of onset, subtype
      of schizophrenia (paranoid, catatonic, hebephrenic types) and symptoms at the
      time of first hospitalization. Symptoms at the time of first hospitalization
      included delusions, hallucinations, disorders of ego consciousness, thought
      disorders, emotional disturbances, lack of spontaneity, catatonic symptoms,
      hypochondriac-cenestopathic symptoms, disorganized behavior, and suicide
      attempts. RESULT: Fifty-six of the 62 patients were followed-up. Six patients
      could not be contacted. Nine of the 56 patients follow-up were dead; two had died
      suddenly and seven had committed suicide. Forty-seven patients were alive, eight
      of which were not under psychiatric treatment, while 39 patients were receiving
      treatment (33 as outpatients, 6 as inpatients). The 47 patients who were still
      living were divided into two groups: 22 were included in the favorable outcome
      group, and 25 in the unfavorable outcome group. No significant differences in
      premorbid status were found. The unfavorable outcome group had an earlier age at
      first contact and age at first admission than the favorable outcome group. In the
      favorable outcome group, acute onset was more common than chronic onset. A
      comparison of psychopathological symptoms at the time of first hospitalization
      between the favorable and unfavorable outcome groups revealed significant
      differences in lack of spontaneity and hypochondriac-cenestopathic symptoms. No
      significant differences were found for any other symptoms. In the favorable
      outcome group, paranoid type was more common than hebephrenic type. DISCUSSION:
      Lack of spontaneity may reflect negative symptomatology, which has been suggested
      to be a predictor of an unfavorable outcome. While hypochondriac-cenestopathic
      symptoms may reflect an insufficient psychic container for the body, which has
      been hypothesized to work as an enabler of body image or imaginary body and an
      enabler of ego function as well. CONCLUSION: First-admission schizophrenic
      patients followed up after a mean period of thirteen years, and of this group
      data could be obtained on 90% of them. Two symptoms (a lack of spontaneity and
      hypochondriac-cenestopathic symptoms) present at the time of first
      hospitalization were observed more frequently in the unfavorable outcome group
      than in the favorable outcome group.

PMID- 11510080
TI  - [Two types of depersonalization--reconsideration from a descriptive
      phenomenological view point].
AB  - The term depersonalization has been vaguely used in clinical contexts and there
      is confusion over its nosological positioning. Although the syndrome has been
      assigned a niche of its own in the European psychiatric taxonomy, the American's
      Diagnostic and Statistical Manual of Mental Disorders (DSM-III, IV) labeled it
      under the term Dissociative Disorder. The latter, which does not agree with the
      classical theory of Janet, seems to have no basis on traditional psychopathology
      and is not derived from any dissociative theories. In this paper the descriptive
      characteristics of depersonalization are discussed with regard to the features of
      "observing self" and the relationship between experiences and selves, according
      to which the authors distinguish two types of depersonalization: an "excessive
      self-reflecting type" and an "absorbed-in-experience type". Whereas the former
      coinsides with the typical depersonalization neurosis, in which excessive self
      reflection plays an important role in reducing the sense of reality, in the
      latter over-absorption in some situations leads the patient to construct a wall
      to block out reality. We suggest that in making a distinction between these two
      types, the psychopathology of depersonalization will be better clarified.

PMID- 11510081
TI  - [Imaging diagnosis of hepatocellular carcinoma: recent progress].

PMID- 11510082
TI  - [Percutaneous tumor ablation therapy for hepatocellular carcinoma: current status
      and future perspective].

PMID- 11510083
TI  - [Change of cardiovascular risk factors after eradication therapy of Helicobacter
      pylori].
AB  - We studied the effect of eradication of Helicobacter pylori (H.P.) on several
      cardiovascular risk factors in patients with peptic ulcer disease. 205 H.P.
      positive patients with peptic ulcer disease were successfully eradicated. Body
      weight (BW), body mass index (BMI), total cholesterol (TC), triglycerides (TG).
      LDL-cholesterol (LDL), HDL-cholesterol, gamma-GTP, uric acid and plasma glucose
      of those were measured before eradication, one year after, and two years after
      eradication. As a control, same parameters were measured in 430 subjects without
      gastroenterological disease including both H.P.-positives and H.P.-negatives.
      Those eradicated patients showed a significant increase in BW, BMI, TC, LDL, TG
      and gamma-GTP over the first one year and two years after eradication. No
      significant difference of any parameters were observed between control groups
      both with and without H.P. No significant difference was observed over one year
      in both control groups. It is suggested that those cardiovascular risk factors
      should be regarded carefully to prevent the acceleration of life-style disease
      after H.P. eradication therapy.

PMID- 11510084
TI  - [Pedunculated GIST of the stomach showing extragastric growth; report of a case].

PMID- 11510085
TI  - [A case of Menetrier's disease caused by cytomegalovirus infection].

PMID- 11510086
TI  - [A case of metastatic ileal cancer from the lung diagnosed endoscopically].

PMID- 11510087
TI  - [A case report of duodenal stenosis caused by retroperitoneum hematoma due to
      rupture of pancreaticoduodenal artery aneurysm].

PMID- 11510088
TI  - [A case of systemic lupus erythematosus presented with severe acute pancreatitis
      as an initial manifestation and improved by intensive care].

PMID- 11510089
TI  - [A case of chronic pancreatitis with diffuse irregular narrowing of the
      pancreatic duct complicated by Sjogren's syndrome and interstitial pneumonia].

PMID- 11510090
TI  - [Evaluation of a new 13CO2 infrared analyzer (UBiT-IR300) for 13C-urea breath
      test].

PMID- 11510091
TI  - [Acute effect of 7% CO2 breathing on lactate, pyruvate and ketone body metabolism
      in healthy subjects].
AB  - Although the effect of hypoxia on the tissue metabolism is well discussed, little
      is known about hypercapnia. To investigate the effect of hypercapnia on
      metabolism, we studied 10 normal subjects in a condition of acute normoxic
      hypercapnia, while they breathed a mixture of gases: 7% CO2, 21% O2 and the
      remainder, N2. Lactate, pyruvate, nonesterified fatty acid (NEFA), and ketone
      bodies were measured by taking blood samples before the study (C), when end tidal
      CO2 reached its peak level (P), and when end tidal CO2 returned to normal (R).
      Pyruvate decreased from 0.66 +/- 0.17 mg/dl from (C) to (P), and reached its
      lowest value in (R). A significant decrement was found in (R) compared with (P)
      (p < 0.05). Lactate increased gradually, but not significantly, from (C) to (R),
      while the lactate/pyruvate ratio increased significantly from (P) to (R). No
      significant change was found in the acetoacetate/3-hydroxybutylate ratio. These
      results suggest that acute hypercapnia may affect the metabolism via the
      mitochondria, and we conclude that hypercapnia may play an important role in the
      disruption of tissue metabolism in man.

PMID- 11510092
TI  - [A focal usual interstitial pneumonia lesion: an important risk factor in diffuse
      alveolar damage--acute exacerbation of a focal usual interstitial pneumonia
      patient].
AB  - The aim of this study was to clarify whether the presence of a focal usual
      interstitial pneumonia lesion (F-UIP) is a risk factor for diffuse alveolar
      damage (DAD). Our subjects were 977 patients (681 males, 296 females, mean age,
      64 years). The incidence of F-UIP increased significantly with age (between 50
      and 60 years, 3% and 8%, p < 0.05; between 60 and 70 years, 8% and 14.1%, p <
      0.05; and between 70 and 80 years, 14.1% and 27.9%, p < 0.01). The mean age of
      the non-UIP group was 64 years, and of the F-UIP group was 75 years, showing
      significance (p < 0.001). The incidence of DAD was higher in the F-UIP group (100
      patients, 30%, p < 0.01) and the diffuse UIP group (60 patients, 30%, p < 0.01)
      than in the non-UIP group (817 patients, 5.3%). Although the causes of DAD were
      various, the presence of F-UIP was a important risk factor of DAD.

PMID- 11510093
TI  - [Clinical analysis of intrapulmonary lymph nodes].
AB  - We encountered 12 cases (9 men, 3 women) of intrapulmonary lymph nodes,
      discovered by chest radiography or chest CT and identified by thoracoscopic lung
      biopsy (in 10 cases), open lung biopsy (1 case) or lobectomy (1 case). We also
      studied the literature related to intrapulmonary lymph nodes in Japanese. Many
      intrapulmonary lymph nodes were found in the lower lung field, few in the upper
      lung field. All intrapulmonary lymph nodes were spherical and were located under
      the pleura, but we were not able in some cases to differentiate them from
      malignancies by the CT scanfindings. We could not diagnose them or rule out
      malignancy before surgery. Pathological findings revealed that all of them showed
      anthracosis. Silicotic changes were found in three cases. We consider that
      thoracoscopy is useful in making a definite diagnosis if peripheral pulmonary
      lesions cannot be diagnosed. We emphasize that intrapulmonary lymph nodes should
      be taken into consideration in differential diagnoses of small nodular lesions in
      the lung.

PMID- 11510094
TI  - [Genetic variation of NADPH/NADH oxidase and susceptibility to diffuse
      panbronchiolitis (DPB) and chronic obstructive pulmonary disease (COPD)].
AB  - Diffuse panbronchiolitis (DPB) and chronic obstructive pulmonary disease (COPD)
      are both characterized by chronic airflow obstruction of unknown etiology. It is
      hypothesized that neutrophils play the major role in the pathogenesis of these
      diseases. Recent studies have suggested that genetic factors may be related to
      individual susceptibility to these diseases. We have investigated the association
      between the C 242 T polymorphism of p 22 phox, a critical subunit of superoxide
      generating NADH/NADPH oxidase, and susceptibility to DPB and COPD. Blood samples
      obtained from both patients with DPB (n = 82), COPD (n = 53), and control
      subjects (n = 82) were used for this genotyping assay; and the polymerase chain
      reaction (PCR) and restriction fragment length polymorphism (RFLP) were performed
      to genotype the gene. The frequency of the C allele was 0.91, 0.92, 0.92 in the
      DPB, COPD, and control groups, respectively. There were no differences in the
      distribution of the genotype of p 22 phox among these groups, either. We
      concluded that there is no association between the C 242 T polymorphism of p 22
      phox, and susceptibility to DPB and COPD.

PMID- 11510095
TI  - [Three cases of pulmonary eosinophilic granuloma].
AB  - CASE 1. A 55-year-old man was admitted because of an abnormality in chest
      radiographs. Chest HRCT showed multiple cystic lesions with thick and thin walls,
      and nodules; and strongly suggested pulmonary eosinophilic granuloma (EG). Open
      lung biopsy revealed granuloma formation and a fibrotic area consistent with EG.
      CASE 2. A 28-year-old woman was admitted because of chest pain and dyspnea. Chest
      radiography revealed bilateral pneumothorax. Chest HRCT showed multiple cystic
      lesions with thick walls involving the entire lung. As lung biopsy revealed,
      proliferative lesions and cavitation containing S-100 protein-positive
      histiocytes, we diagnosed this case as pulmonary EG in the active stage. CASE 3.
      A 32-year-old woman was admitted because of dyspnea. Chest CT showed bullous
      changes in the lung. As an open lung biopsy revealed, honeycomb changes with S
      100 protein-positive histiocytes, this case was diagnosed as the regressive phase
      of EG. It is known that the chest radiography and HRCT findings of EG are
      characteristic and vary with the stage, so a surgical lung biopsy is necessary
      for diagnosis of EG. It is considered that the prognosis of the active phase of
      EG involving the entire lung is poor.

PMID- 11510096
TI  - [Pulmonary nocardiosis associated with nephrotic syndrome].
AB  - A 70-year-old man treated for 6 months with prednisolone for nephrotic syndrome,
      was referred to our pulmonary division because of a nodule in the right lower
      lung field. Nocardia asteroides was isolated from the culture of the percutaneous
      lung aspiration, and the case was diagnosed as pulmonary nocardiosis. The lesion
      disappeared after 2 months of therapy with sulfamethoxazole/trimethoprim (1,600
      mg/320 mg once a day). Though it had been given prophylactically (800 mg/160 mg
      twice a week) for the prevention of pneumocystis carinii pneumonitis.

PMID- 11510097
TI  - [Bilateral chylothorax as initial manifestation of gastric cancer].
AB  - We describe a case in which bilateral chylothorax was the initial presenting
      manifestation of a gastric cancer (scirrhous type). A 58-year-old woman was
      admitted because of acute right subclavian vein thrombosis. Following admission,
      she complained of dyspnea on effort and on the 14th hospital day chest X-ray
      examination revealed bilateral pleural effusion. Biochemical tests of the pleural
      fluid detected chyle, and cytological examinations revealed mucinous
      adenocarcinoma bilaterally. An upper gastrointestinal examination revealed
      gastric cancer (scirrhous type). Carcinoma of the stomach has very rarely been
      described as the cause of chylothorax, but our findings indicate the need to rule
      out a gastric neoplasm in patients with chylothorax of no clear cause.

PMID- 11510098
TI  - [A case of desmoplastic malignant pleural mesothelioma].
AB  - A 71-year-old woman with no history of asbestos exposure was referred to our
      hospital for evaluation of mediastinal soft tissue density. Six months prior to
      the admission, she had developed back pain and had been diagnosed as having
      intercostal neuralgia. Since the symptoms progressed, she was referred to another
      hospital. While chest radiography revealed no abnormality, chest computed
      tomography showed the prominence of mediastinal soft tissue, extending to the
      left hilum and partially destroying the nearby vertebrae. However, no pleural
      effusion was noted. After admission, a thoracoscopic examination was performed,
      and a whitish mass was found on the pleural surface partially adhering to the
      chest wall. Histological examination of the biopsied material showed dense areas
      of collagenous tissue with small foci of slightly atypical spindle cells. These
      findings led to the diagnosis of desmoplastic malignant pleural mesothelioma. The
      patient was treated with combined chemo-radiotherapy, but the response to this
      treatment was unclear. To date, reports for this subgroup of malignant
      mesothelioma are still rare.

PMID- 11510100
TI  - [Acute eosinophilic pneumonia with positive response to smoking challenge test,
      suggesting the involvement of health food].
AB  - A 17-year-old girl was admitted to our hospital because of acute febrile illness,
      progressive dyspnea and severe hypoxemia. Chest radiography and HRCT showed
      bilateral diffuse ground-glass opacities, consolidation, Kerley lines and pleural
      effusion. Analysis of bronchoalveolar lavage fluid showed 41.9% eosinophils, and
      a transbronchial lung biopsy revealed infiltration of eosinophils into the
      alveolar septa and mild alveolar septal edema. The patient's condition was
      improved immediately by corticosteroid therapy. She had begun smoking and taking
      health food (chitosan) 3 months before the admission. A smoking challenge test
      was positive and a drug-induced lymphocyte stimulation test for chitosan was
      positive. These findings suggested acute eosinophilic pneumonia caused by smoking
      and health food. The concentration of interleukin-5 (IL-5) in the serum and
      BALF/granulocyte colony-stimulating factor (G-CSF) in the serum on admission were
      very high, but decreased after the improvement. Therefore, it is likely that IL-5
      and G-CSF are important in the onset of acute eosinophilic pneumonia.

PMID- 11510099
TI  - [CA19-9-producing idiopathic pulmonary fibrosis with diffuse alveolar damage and
      a high titer of KL-6--an autopsy case].
AB  - A 73-year-old woman with CA19-9-producing idiopathic interstitial pneumonia was
      admitted to the hospital when her condition was exacerbated. Chest radiography
      and computed tomography showed an additional patchy shadow. The serum CA19-9
      level remained high during the clinical course, whereas KL-6 increased only at
      exacerbation. No therapy was effective, and the patient died 5 days later. The
      lung obtained at autopsy showed hyaline membrane formation, hemorrhage, and
      squamous metaplasia, suggesting that acute exacerbation had resulted in diffuse
      alveolar damage. Immunohistochemical staining using either anti-CA19-9 mAb or
      anti-KL-6 mAb showed the localization of CA19-9 and KL-6 antigen in the dilated
      bronchiolar epithelial cells. In conclusion, although CA19-9 can be an indicator
      for the degree of fibrotic and destructive change of lung structure, KL-6 seemed
      more sensitively to reflect the disease state of the diffuse alveolar damage.

PMID- 11510101
TI  - [A case of acute pulmonary embolism associated with squatting].
AB  - The patient was a 69-year-old man with a 3-year history of diabetes mellitus
      accompanied by cerebral infarction and arteriosclerosis obliterans of the lower
      extremities. After squatting to clean a car, the patient began to experience
      dyspnea. A blood gas analysis was performed upon admission, and the patient's
      PaCO2 and PaO2 levels were found to be low. Examination of a blood sample
      revealed elevated FDP, FDP-D dimer and platelet factor 4 levels. A perfusion lung
      scan showed multiple defects in both lungs, but no abnormal findings were
      detected on a ventilation scan. A pulmonary angiogram showed an interrupted blood
      flow in branches A9 + 10 of the left pulmonary artery. Accordingly, a pulmonary
      embolism was diagnosed. Squatting may have caused a partial obstruction of the
      venous return from the lower extremities by compression of the inguinal region
      and may have been a predisposing cause of the thrombosis. To our knowledge, such
      cases of pulmonary embolism triggered by the act of squatting are very rare.

PMID- 11510102
TI  - [A patient with lymphoma of mucosa-associated lymphoid tissue (MALT) and
      adenocarcinoma in the same tumor of the lung].
AB  - A 60-year-old woman with no symptoms was found to have a mass shadow in the left
      lower lobe of the lung on chest radiography. Open lung biopsy and left lower
      lobectomy were performed. Histopathological study of the specimen revealed two
      distinct neoplasms. One tumor was a low grade B-cell lymphoma of mucosa
      associated lymphoid tissue (MALT) of the lung, while the other was an
      adenocarcinoma. The two neoplasms were admixed to form a composite tumor.

PMID- 11510103
TI  - [Drug-induced interstitial pneumonia associated with inhalation of fibrinolysin
      deoxyribonuclease (ElaseR)].
AB  - A 73-year-old man was referred to our department because of sputum production and
      fever. He had under-gone a total laryngectomy for laryngeal cancer. His chest
      radiograph showed patchy ground-glass shadows in both lung fields. He was treated
      with antibiotics for pneumonia, but his symptoms continued, and the size of the
      patchy shadows in the chest radiograph increased. Inhalation therapy with ElaseR
      had been started from one day before fever arose. Withdrawal of ElaseR treatment
      resolved his symptoms. We therefore suspected drug-induced interstitial
      pneumonia. Transbronchial lung biopsy specimens showed infiltration of
      lymphocytes in the alveolar septa and thickening of those septa. A
      bronchoalveolar lavage revealed an increased number of lymphocytes, and the
      CD4/CD8 ratio was 0.3. A drug lymphocyte stimulation test (DLST) with peripheral
      blood lymphocytes was strongly positive (S.I. 2127%) for ElaseR. The anti-nuclear
      antigen (ANA) was detected (x640), and the anti-single strand DNA antibody titer
      was also high (123.4 IU/ml). About 10 weeks after the withdrawal of ElaseR, the
      infiltrative shadows and the abnormal laboratory findings improved spontaneously.
      On the basis of these findings, we arrived at a diagnosis of drug-induced
      interstitial pneumonia associated with inhalation of ElaseR.

PMID- 11510104
TI  - [A case of sarcoidosis acutely aggravated with high fever and diffuse
      interstitial pulmonary infiltrates].
AB  - We present a case of sarcoidosis acutely aggravated with high fever and diffuse
      interstitial pulmonary infiltrates in a female patient at the age of 64.
      Sarcoidosis was diagnosed in another hospital as a result of iritis, chest
      radiography findings, and a negative reaction in a tuberculin skin test. She was
      admitted to our hospital because of dyspnea and a high temperature of 39 degrees
      C in February 1994. A marked hypoxemia (PaO2 46.5 torr) was found in arterial
      blood gas analysis. Chest radiography revealed a bilateral diffuse reticulo
      nodular shadows, and chest CT showed ground glass opacity predominant
      posteriorly. Analysis of bronchoalveolar lavage fluid revealed an increase in
      lymphocytes and an increased ratio of CD4 to CD8 T lymphocyte. Transbronchial
      lung biopsy revealed lymphocytic alveolitis and proliferation of epithelioid cell
      granulomas in the alveolar septa and intraalveolar spaces. The patient was
      treated for deterioration of sarcoidosis with 40 mg of prednisolone and her
      respiratory status and the radiographic findings improved rapidly. With dose
      tapering of prednisolone, dyspnea and deterioration of the radiographic findings
      occurred, but with addition of a weekly low dose of methotrexate, dose reduction
      of prednisolone was achieved.

PMID- 11510105
TI  - [Electrodiagnosis of diabetic retinopathy--history and recent advance].

PMID- 11510106
TI  - [Relationship between glycoxidation and cytokines in the vitreous of eyes with
      diabetic retinopathy].
AB  - PURPOSE: To investigate the correlations among pentosidine, an advanced glycation
      end product, and related cytokines [vascular endothelial growth factor(VEGF),
      transforming growth factor(TGF)-beta 2, and monocyte chemotactic protein(MCP)-1],
      and active oxygen in the vitreous of patients with diabetic retinopathy(DR).
      METHODS: Vitreous samples from 43 eyes undergoing vitrectomy to treat DR were
      divided into four subgroups and analyzed. Vitreous samples from 21 eyes of
      patients with no systemic conditions were age- and sex-matched controls. The
      vitreous levels of pentosidine, cytokines, and hydrogen peroxide (H2O2) were
      determined by high performance liquid chromatography, enzyme-linked immunosorbent
      assay, and titanium-hydrogen peroxide colorimetric method respectively. RESULTS:
      The levels of pentosidine, VEGF, total TGF-beta 2, and MCP-1 in the vitreous
      samples of eyes with DR were significantly higher than in the controls(p < 0.01).
      Significant correlation(p < 0.01) was found between pentosidine and VEGF,
      pentosidine and H2O2, H2O2 and VEGF, and total TGF-beta 2 and MCP-1(r = 0.62,
      0.58, 0.65, and 0.59, respectively). CONCLUSIONS: These results suggest that the
      elevated levels of the glycoxidation product pentosidine may have caused
      increased levels of VEGF in the vitreous of DR patients. Increased levels of
      total TGF-beta 2 and MCP-1 together may also play an important role in the
      development of DR.

PMID- 11510107
TI  - [Effect of different concentrations of tranilast on posterior capsule
      opacification].
AB  - PURPOSE: To evaluate the effect of different concentrations(0.5, 1.0, 2.0%) of
      tranilast eyedrops in preventing fibrous posterior capsule opacification (PCO) in
      rabbits. METHODS: Experimental phacoemulsification procedures and in-the-bag
      placement of intraocular lens(IOL) implant were performed. An anterior eye
      segment analysis system(EAS-1000, Nidek Co, Ltd) was used to evaluate the degree
      of PCO during 5 weeks after surgery. RESULTS: The development of PCO was
      significantly suppressed in the eyes treated with tranilast eyedrops from 1 week
      after surgery. The mean PCO density after treatment with 0.5% tranilast was 59.1
      +/- 9.3 (mean deviation +/- standard error) and 57.1 +/- 8.2, while for 1.0%
      tranilast it was 40.1 +/- 6.8 and 46.6 +/- 8.4, and for 2.0% tranilast it was
      38.5 +/- 6.0 and 37.5 +/- 5.6 (computer compatible tape, CCT) at 1 week and 5
      weeks, respectively. In the control group, the mean PCO density was 89.3 +/- 10.4
      and 137.4 +/- 32.8 at 1 week and 5 weeks, respectively(p < 0.05). However, no
      significant statistical difference was observed in any of the findings for the 3
      different tranilast concentrations. CONCLUSION: These results suggest that the
      0.5% tranilast eyedrops, which are already available on the market, are
      sufficiently effective for inhibiting PCO.

PMID- 11510108
TI  - [An ultrasound biomicroscopic study of eyes after non-penetrating
      trabeculectomy].
AB  - PURPOSES: We studied the control of intraocular pressure(IOP) by various types of
      blebs after non-penetrating trabeculectomy(NPT) and the difference between bleb
      formation after penetrating trabeculectomy(PT) and that after NPT. METHODS: The
      filtering blebs of 45 yeys from 40 patients after NPT were studied using
      ultrasound biomicroscopy. They were grouped into four types, and the space under
      the scleral flap was classified into three types. The filtering blebs and the
      space under the scleral flap were correlated with IOP level. RESULTS: Overall,
      40% of the blebs were L(low-reflective) type, 16% H(high-reflective) type, 16% E
      (encapsulated) type, and 29% F(flattened) type, but in good IOP control cases 59%
      of the blebs were L type, 14% H type, 14% E type, and 14% F type. L type blebs
      were found in 94% of eyes with good IOP control. CONCLUSION: Though filtering
      blebs of the L type could produce sufficient IOP reduction, blebs after NPT
      showed a greater tendency to become flattened than after PT. Additional
      systematic therapy must be designed to maintain the L type of filtering blebs
      after NPT.

PMID- 11510109
TI  - [Clinical features of idiopathic macular holes-differences between sexes and
      stages].
AB  - PURPOSE: The purpose of this study was to evaluate the differences in the
      clinical features of idiopathic macular holes between sexes and stages. METHODS:
      Five hundred and twenty-six eyes of 480 patients with stage 3 or 4 idiopathic
      macular hole that had undergone vitrectomy were observed consecutively in this
      study. The each stage ratio, bilaterality, and affected eye were examined and the
      differences in age, hole duration, hole size, visual acuity, refractive power,
      axial length, and corneal refractive power were evaluated. RESULTS: Twenty-six %
      of the cases were stage 4 in males and 31% in females. There were no significant
      differences in bilaterality or affected eye between the sexes. Younger age and
      larger size were found in females of stage 3. Larger size was found in stage 4.
      More myopic eye and longer axial length were found in males of stage 4. There
      were no significant differences in hole duration and visual acuity between sexes
      or stages. CONCLUSIONS: In females the onset of macular hole occurred at a
      younger age than in males, size of the hole was larger from an earlier stage, and
      refractive power was less myopic. More myopic eye and longer axial length were
      found in stage 4, especially in males. This fact might be related to the
      existence of posterior vitreous detachment. We concluded that there were some
      differences in the mechanism of the onset and the progression of idiopathic
      macular hole between males and females.

PMID- 11510110
TI  - [Long-term results of vitrectomy for complications of proliferative diabetic
      retinopathy].
AB  - PURPOSE: To evaluate the long-term results of vitrectomy for complications of
      proliferative diabetic retinopathy. METHODS: Five-year follow-up examinations
      were obtained on 33 eyes of 24 patients that underwent vitrectomy. The
      preoperative status of macula was no detachment(group 1, 9 eyes), macular
      detachment(group 2, 17 eyes), and traction macular fold (group 3, 7 eyes).
      RESULTS: The retina was successfully reattached in 17 eyes(100%). The final
      visual acuity obtained was as follows: 75% of the eyes had acuity of 0.1 or
      better in group 1, 65% in group 2, and 86% in group 3; 44% had acuity of 0.5 or
      better in group 1, 24% in group 2, and 14% in group 3; and 11% had acuity of 0.05
      or worse in group 1, 18% in group 2, and 0% in group 3. 11% of the final visual
      acuity was worse than the postoperative best visual acuity(three lines or more)
      in group 1, 29% in group 2, and 14% in group 3. The causes of worsening in vision
      were optic or macular atrophy. CONCLUSIONS: Vitrectomy for complications of
      proliferative diabetic retinopathy is valuable in improving the patient's visual
      acuity.

PMID- 11510111
TI  - [Scotopic threshold response in noninsulin-dependent diabetes mellitus patients
      with good HbA1c level and ophthalmoscopically intact fundus].
AB  - PURPOSE: To evaluate behavior of the scotopic threshold response(STR) and the
      oscillatory potentials(OPs) of the electroretinogram in noninsulin-dependent
      diabetes mellitus(NIDDM) patients without retinal abnormalities. METHODS: The STR
      and the OP 1-3 were recorded from 15 eyes of 15 NIDDM patients aged from 45 to 63
      years old with good HbA1c level and ophthalmoscopically intact fundus. As a
      control group, 8 eyes of 8 age-matched normal subjects were used. The amplitude
      and the implicit time of the STR as well as the amplitudes and the peak latencies
      of OP 1-3 were measured. RESULTS: The mean amplitude and the mean implicit time
      of the STR in the NIDDM group did not differ significantly from those in the
      control group. The mean amplitudes and the mean peak latencies of the OP 1-3 also
      showed no significant differences between the NIDDM and control groups.
      CONCLUSIONS: The STR in NIDDM patients remains normal with good HbA1c level and
      ophthalmoscopically intact fundus.

PMID- 11510112
TI  - [Changes in the second-order kernel component obtained by the techniques of the
      multifocal electroretinogram in early stages of diabetes mellitus].
AB  - PURPOSE: To detect changes in retinal function in diabetic eyes without
      ophthalmoscopic retinopathy and to find a clue for differential origins of the
      second-order kernel of the multifocal electroretinogram(m-ERG). METHODS: m-ERGs
      were recorded from eyes of 22 healthy control subjects and 21 patients with
      diabetes mellitus(DM) by 19-hexagonal-element stimulus at stimulus intensities of
      20, 63, 100, 200 and 331 cd/m2(VERIS III, Tomey). The response densities and the
      peak latencies of the first-order kernel(P 1) and the second-order kernels(P 2, P
      3) were compared between the DM and the control groups. Full-field ERGs were also
      recorded from the same patients and compared with the results of m-ERGs. RESULTS:
      The response densities of P 1 and P 2 in the DM group were significantly(p <
      0.05) larger than those in the control group. The response of the full-field ERG
      in the DM group did not significantly differ from that in the control group. The
      components of the m-ERG were divided into two groups based on their behavior to
      stimulus intensity changes: P 1 together with P 2 and P 3. With increase in the
      stimulus intensity, the response densities of P 1 and P 2 increased
      significantly(p < 0.05), while the response densities of P 3 did not change
      significantly. CONCLUSION: The fact that the response densities in the DM group
      were greater than those in the control group supports the hypothesis that the
      retinal blood flow increases in the early stage of diabetes. m-ERG is therefore
      beneficial to ascertain subclinical retinal changes and to evaluate the retinal
      function of early diabetic patients. Since the P 2 and P 3 differed in behavior
      according to the stimulus intensities, it can be inferred that origin of the P 2
      of the second order kernel is different from that of P 3.

PMID- 11510113
TI  - [Influence of cyclosporin on steroid-induced cataract].
AB  - PURPOSE: To study the effect of cyclosporin on steroid-induced cataract in
      patients after renal transplantation. SUBJECTS AND METHODS: 140 patients who
      received renal transplantation and ophthalmological examinations before and over
      12 months after surgery at Kanazawa Medical University were investigated
      retrospectively. The subjects were divided into the following two groups: the
      conventional therapy group(Group C) who were administered azathioprin and
      methylprednisolone and the triple therapy group(Group T) who were administered
      azathioprin, methylprednisolone and cyclosporin. There were 73 subjects in group
      C and 67 in group T. Judgement of steroid cataract followed Crew's classification
      and steroid cataract was diagnosed when vacuoles or opacity were seen in the
      posterior subcapsular region. Subjects that had any lens opacity before renal
      transplantation were excluded. RESULTS: The total dose of systemic steroid during
      the first year and in the final observation period in group T was significantly
      higher than in group C. The prevalence of steroid cataract was 55% and 63% for
      the 1st year, 72% and 89% for the 2nd year, 74% and 92% for the 3rd year and 83%
      and 96% for the 5th year in groups C and T, respectively. By the third year, the
      rate of subjects whose corrected visual acuity was less than 0.8 or who received
      cataract surgery was significantly higher in group T than in group C. There was
      no significant difference in the total dose between the subjects with cataract
      over grade I and those of grade 0 and I in both groups C and T. In group C, the
      total dose of steroid pulse therapy was significantly higher in the subjects with
      steroid cataract over grade I than in those with grade 0 and I. CONCLUSIONS:
      Using cyclosporin, although the total dose of systemic steroid was decreased, the
      rate of steroid cataract increased. Cyclosporin may accelerate the development of
      steroid cataract. Steroid pulse therapy is considered to be a risk factor for
      developing steroid cataract.

PMID- 11510114
TI  - [Ocular complications in patients infected with human immunodeficiency virus seen
      at the Acquired Immunodeficiency Syndrome Clinical Center].
AB  - PURPOSE: To examine the ocular complications in patients infected with human
      immunodeficiency virus(HIV) in Japan. METHODS: The medical records of 322
      patients seen at the acquired immunodeficiency syndrome(AIDS) Clinical Center
      from July 1, 1997 through December 31, 1998 were reviewed, and the HIV-associated
      ocular complications were correlated with serum CD 4+ T-lymphocyte counts.
      RESULTS: Ocular complications were found in 51 patients: 35 cases with retinal
      microvasculopathy, 17 cases with cytomegalovirus retinitis(9 quiescent, 6 active,
      and 2 recurrent), and 1 case each with tuberculous uveitis, phthisis bulbi after
      necrotizing herpetic retinopathy, conjunctival Kaposi's sarcoma, papilledema,
      divergence palsy, hemianopia, and abducens palsy. Retinal microvasculopathy was
      present in patients with CD 4+ T-lymphocyte counts above 500/mm3, but was more
      common in patients with cell counts below 200/mm3. Among 6 patients with active
      cytomegalovirus retinitis, 5 patients had a CD 4+ T-lymphocyte count below 50/mm3
      at the onset of retinitis, while one patient developed retinitis after the cell
      count increased to over 200/mm3 with highly active antiretroviral therapy.
      CONCLUSION: Cytomegalovirus retinopathy may occur in patients with a CD 4+ T
      lymphocyte count of more than 200/mm3.

PMID- 11510115
TI  - [The ability of frequency doubling technology to detect abnormality of visual
      function in early glaucoma].
AB  - PURPOSE: To evaluate the ability of the Frequency Doubling Technology(FDT)
      threshold test in detecting abnormality of visual function in early glaucoma
      patients. SUBJECTS AND METHOD: The C-20 full threshold test of FDT was performed
      on 34 normal-tension glaucoma(NTG) patients and 39 primary open-angle
      glaucoma(POAG) patients with visual field defects limited to the upper or lower
      hemi-field as detected by Humphrey Field Analyzer(HFA) and on 79 normal control
      subjects. Optic disk findings and FDT results corresponding to the intact hemi
      field were evaluated. FDT abnormalities in normal subjects were calculated as
      false positive rates in FDT. RESULT: The sensitivity and specificity of FDT,
      calculated based on optic disk findings, were 75.0% and 61.1% in POAG, and 61.1%
      and 66.7% in NTG, respectively, while the false positive rate in normal subjects
      was 11.4%. CONCLUSION: FDT can detect glaucomatous functional abnormality earlier
      than HFA.

PMID- 11510116
TI  - [Review 7. Leukocoria].

PMID- 11510117
TI  - [Therapies for infections diseases in the 21st century. The role of minocycline
      among common treatments--focused on oral formulations(discussion)].

PMID- 11510118
TI  - [Comparative studies on activities of antimicrobial agents against causative
      organisms isolated from patients with urinary tract infections (1999). I.
      Susceptibility distribution].
AB  - The bacterial strains isolated from patients diagnosed as having urinary tract
      infections (UTIs) in 9 institutions in Japan were supplied between the period of
      August 1999 to July 2000. Then, the susceptibilities of them to many kinds of
      antimicrobial agents were investigated. The number of them were 499 strains. The
      breakdown of these strains was Gram-positive bacteria as 31.3% and Gram-negative
      bacteria as 68.7%. Susceptibilities of these bacteria to antimicrobial agents
      were as follows; vancomycin (VCM), ampicillin (ABPC) and imipenem (IPM) showed
      strong activities against Enterococcus faecalis. The increase of low-susceptible
      strains which was noticed in the former year showed a slight recovery in this
      year. VCM showed a strong activity against MRSA preventing growth of all strains
      with 1 microgram/ml. In addition, the activity of arbekacin (ABK) was also strong
      with the MIC90 of 2 micrograms/ml against MRSA. However, MSSA and MRSA showing
      low susceptibilities were detected in one strain each (MIC: 16 micrograms/ml and
      32 micrograms/ml, respectively). Carbapenems showed high activities against
      Citrobacter freundii and Escherichia coli. Meropenem (MEPM) prevented growth of
      all strains within 0.125 microgram/ml. Quinolone resistant E. coli decreased in
      this year compared with those in the last year, that percentage was less than 5%.
      Almost all drugs showed strong activities against Klebsiella pneumoniae and
      Proteus mirabilis. MEPM and carumonam (CRMN) prevented growth of all strains
      within 0.125 microgram/ml. On the other hand, one strain of K. pneumoniae showing
      resistance to cefaclor (CCL) and one strain of P. mirabilis showing low
      susceptibility to most of cephems were detected. Against Pseudomonas aeruginosa,
      almost drugs were not so active. The MIC90s of carbapenems were 8 micrograms/ml
      and those of all other drugs were more than 16 micrograms/ml.

PMID- 11510120
TI  - Implication of BRCA1 gene in breast cancer.
AB  - Breast cancer susceptibility gene (BRCA1) is known to be responsible for
      hereditary breast and ovarian cancer. This gene is highly penetrant conferring a
      risk for 0.92 by the age of 70. Germline mutation in this gene leads to
      susceptibility to breast and ovarian cancer, with a genotype phenotype
      correlation. Frequency of mutations of this gene in normal population of breast
      cancer is low suggesting that the effort of primary screening for BRCA1 gene
      should be restricted to only familial cases with a strong history of breast and
      ovarian cancer. Recent studies indicate that BRCA1 is a tumor suppressor gene
      responsible for both normal development and carcinogenesis of the breast. Normal
      function elucidated so far, reveal BRCA1 to be a multifunctional protein involved
      in DNA repair, cell cycle regulation and transcription. There is circumstantial
      evidence that gene interacts with p53, a protein involved in cell cycle control,
      DNA repair and apoptosis.

PMID- 11510119
TI  - [Comparative studies on activities of antimicrobial agents against causative
      organisms isolated from patients with urinary tract infections (1999). II.
      Background of patients].
AB  - Five-hundred forty four bacterial strains isolated from 412 patients diagnosed as
      having urinary tract infections (UTIs) in 9 institutions in Japan were supplied
      between the period of August 1999 to July 2000. Then, the clinical background of
      patients were investigated such as sex, age and type of infections, infections
      and kind of bacteria, frequency of isolation of bacteria by age and infections,
      bacteria and infections by timing of administration of antibiotics, and bacteria
      and infections by surgical procedures. About the relationship between age and sex
      of patients and type of infections, the number of male patients aged less than 50
      years was few, and complicated UTIs without indwelling catheter was the most
      frequent. In females, the number of patients aged less than 20 years was few.
      Complicated UTIs without indwelling catheter was the most frequent among female
      patients aged between 40 to 59 years, in other age groups, uncomplicated UTIs was
      most frequent. As for type of infections and kind of bacteria, Escherichia coli
      decreased when the infections became complicated, and Pseudomonas aeruginosa and
      Enterococcus faecalis increased when the infection became complicated.
      Considering this result by age of patients, isolation frequency of E. coli was
      gradually decreased with aging in patients aged more than 20 years with
      uncomplicated UTIs or complicated UTIs without indwelling catheter. The isolation
      frequencies of E. faecalis and Staphylococcus aureus were gradually increased
      with aging in complicated UTIs without indwelling catheter. In patients with
      complicated UTIs with indwelling catheter, there was no difference between age
      group, and P. aeruginosa and E. faecalis were frequently isolated. As for type of
      causative organisms in UTIs before and after the administration of antibiotics,
      the isolation of bacteria was remarkably decreased after administration in
      patients with uncomplicated UTIs and complicated UTIs without indwelling
      catheter. E. coli decreased after administration of antibiotics, and P.
      aeruginosa and E. faecalis increased after administration in patients with all
      infections. As for type of causative organisms in UTIs and surgical procedures,
      E. coli were more frequently isolated in patients with uncomplicated UTIs when
      surgical procedures were experienced. Also, Klebsiella spp. and E. faecalis were
      more frequently isolated in patients with surgical procedures. However, in
      complicated UTIs, type of causative organisms had no relationship with surgical
      procedures.

PMID- 11510121
TI  - Lipochitooligosaccharides and legume Rhizobium symbiosis--a new concept.
AB  - Legume-Rhizobium symbiosis is a multistep process characterized by the formation
      of root nodules on the host plant. A number of genes from both symbiotic partners
      share information during the interaction process. Nodulation genes (nod, nol and
      noe) have been classified as common nodulation genes and host specific (hsn)
      nodulation genes. Though common nodulation genes are enough to form root nodules,
      host specific nodulation genes are needed for specific interaction leading to
      formation of functional nodules. Core lipochitooligosaccharides (LCOs), the
      products of common nodulation genes are modified by the action of host specific
      nodulation genes. LCOs seem to be present in legumes as well as nonlegume and are
      known to act as a morphogen by acting as auxin-transport inhibitor. The
      understanding of Nod factor may contribute to reveal complex biological functions
      such as developmental regulation, signal transduction and plant morphogenesis.

PMID- 11510122
TI  - Cloning and expression of an actinokinase gene from a thermophilic Streptomyces
      in Escherechia coli.
AB  - A thermophilic Streptomyces megasporus strain SD5, could secrete a new
      fibrinolytic (actinokinase) at 55 degrees C. The gene (ackS) encoding
      actinokinase was isolated from the chromosomal DNA of S. megasporus SD5 and
      cloned in different hosts and vectors. The expression was obtained in E. coli
      JM109 using Cla I linearized pBR322 as vector (pSR 500). The recombinant E. coli
      containing pSR 500 expressed active actinokinase but the expression was low and
      the recombinant was unstable in liquid culture. Deletion analysis revealed that
      removal of Bam H I-Sal I fragment from down stream and Cla I-EcoRI from upsream
      enhanced the stability and expression of ackS in both solid and liquid media. For
      over expresion, the ackS gene was cloned in E. coli C 600 using Bam HI linearized
      pT7-7. This seemed to be the most suitable host vector system. The recombinant
      and native form of actinokinase exhibited similar characteristics. Actinokinase
      was the first thrombolytic enzyme from a thermophile to be cloned and over
      expressed in a mesophilic heterologous expression system.

PMID- 11510123
TI  - Pancreatic polypeptide cells of rat pancreas after chronic ethanol feeding.
AB  - Male Wistar rats, (2 months old) were randomly divided into two groups according
      to the diet offered (C-control and E-ethanol treated rats). Final body weight was
      significantly increased but pancreatic weight as a percentage of body weight was
      decreased in ethanol treated rats. Volume density, number of pancreatic poly
      peptide (PP)-cells per islet and per micron 2 of islet were significantly
      increased. PP-cells were abundant and occupied the whole periphery of islets in
      the splenic part of the pancreas. Those cells showed strong immunopositivity. At
      the ultrastructural level PP granules had predominantly less electron density.
      The mean diameter of PP granules was significantly increased and the number of
      granules of larger diameter was greater in the E group of rats, than in the
      controls.

PMID- 11510124
TI  - Anticonvulsant effect of cytoskeletal depolymerizers in combination with
      potassium channel opener and adenylate cyclase activator; a causative link with
      nerve growth factor?
AB  - Anticonvulsant effect of cytoskeletal depolymerizing drugs in combination with
      potassium channel (KATP) opener and adenylate cyclase activator was evaluated in
      animal models of epilepsy. Seizures were induced in the animals by subjecting
      them to maximal electroshock (MES) or by injecting a chemical convulsant,
      pentylenetetrazole (PTZ). Moreover a correlation with the nerve growth factor
      (NGF) was also investigated. The anticonvulsant effect of minoxidil (1200
      micrograms/kg i.p.) and Deacetylforskolin (600 micrograms/kg i.p.) was
      significantly enhanced in the mice pre-treated with cytoskeletal depolymerizing
      drugs. On the other hand nerve growth factor potentiated the convulsive
      phenomenon and decreased the seizure threshold in both the electroshock and
      chemically induced convulsions. Another interesting feature was the interaction
      of cytochalasin B, a microfilament disrupter in preventing the action of mNGF and
      PTZ. This study demonstrates the importance of interaction between cytoskeletal
      structures and signalling molecules in determining the convulsive threshold. This
      study clearly points to the importance of the nerve growth factor in convulsive
      phenomenon.

PMID- 11510125
TI  - Short-term effects of thyroid hormones on lipogenic enzymes and 14C-acetate
      incorporation into various lipid classes: in vivo and in vitro studies.
AB  - Short-term effect of 3,5,3'-triiodothyronine (T3) and 3,5-diiodothyronine (T2) on
      lipid metabolism in the liver of Anabas testudineus was examined. In vivo
      injections of both T3 and T2 at a concentration of 10 ng/g body weight increased
      malic enzyme (ME), glucose-6-phosphate dehydrogenase (G6PDH) and 6
      phosphogluconate dehydrogenase (6PGDH) activity compared to 6-propylthiouracil (6
      PTU) treated group. Treatment of 6-PTU results in the accumulation 14C-acetate
      into fat and thyroid hormones' treatment reduce it. In vitro experiments show
      that malic enzyme activity is augmented only by high concentration of T3 (10(-7)
      M) where as all concentrations of T2 increase its activity. In vitro studies with
      T3 showed a biphasic effect on cholesterol content. Conversely T2 in vitro,
      reduced cholesterol content with all concentrations. From these results it can be
      concluded that both T3 and T2 have short-term effect on lipid metabolism in
      Anabas.

PMID- 11510126
TI  - Protective effect of N-acetylcysteine in isoniazid induced hepatic injury in
      growing rats.
AB  - Status of oxidative/antioxidative profile was the mechanistic approach to
      inumerate the nature of protection by N-acetylcysteine (NAC) in isoniazid (INH)
      exposed experimental animals. Analysis of lipid peroxidation, thiol levels,
      cytochrome P450, superoxide dismutase (SOD), catalase, glutathione peroxidase,
      reductase and transferase were estimated in liver along with the body and liver
      weight of animals and histological observations. Isoniazid exposure to animals
      resulted in no change in body and liver weights. Thiols, lipid peroxidation,
      catalase, SOD glutathione peroxidase, reductase, transferase and cytochrome P450
      levels were altered with INH exposure. Supplementation of NAC with INH protected
      the animals against hepatotoxic reactions by minimizing the free radical induced
      tissue injury and overall maintenance of the endogenous scavengers of free
      radicals.

PMID- 11510127
TI  - Sub chronic toxicity studies of lactulose in rats.
AB  - Lactulose has profound health benefits by way of increasing bifidobacterial flora
      in the intestine of infants thereby protecting them against enteric infection,
      constipation and systemic encephalopathy. In the present study to assess the sub
      chronic toxicity of lactulose syrup, the rats were fed on a basal feed
      supplemented with lactulose syrup at 0.5, 1.0, 2.0 and 5.0% for a period of 21
      weeks. Monitoring of food consumption, gain in body weight and physical
      observations did not reveal any treatment-related toxicity in any of the group of
      rats. Terminal autopsy also did not reveal any signs of toxicity. Further, no
      significant alterations in relative organ weight, serum biochemistry and
      urinalysis were observed up to 1% lactulose supplementation level. The results
      suggest that supplementation of lactulose in the diet does not produce any
      toxicity at the doses tested.

PMID- 11510128
TI  - Antioxidant activity of brahma rasayana.
AB  - Free oxygen radical scavenging activity of brahma rasayana (BR) was studied by in
      vitro and in vivo models. Addition of aqueous extract of BR was found to scavenge
      the lipid peroxides already present in rat liver homogenate (IC50 700
      micrograms/ml) and inhibit the lipid peroxide generated by Fe(2+)-ascorbate (IC50
      2600 micrograms/ml) and Fe(3+)-ADP-ascorbate system (IC50 1200 micrograms/ml). BR
      was found to scavenge the hydroxyl radical generated by Fenton reaction (IC50
      7400 micrograms/ml) and superoxide generated by photoreduction of riboflavin
      (IC50 180 micrograms/ml). BR was also found to inhibit the nitric oxide radical
      generated in vitro from sodium nitroprusside (IC50 5.5 micrograms/ml). Oral
      administration of BR (50 mg/dose/animal) was found to inhibit the PMA induced
      superoxide generation in mice peritoneal macrophages. Oral administration of BR;
      10 and 50 mg/dose/animal was also found to inhibit the nitrite production in
      peritoneal macrophages and percentage inhibition was 25.2% and 37.8%
      respectively. These results indicate significant antioxidant activity of BR in
      vitro and in vivo.

PMID- 11510129
TI  - Acute and subchronic toxicity of aflatoxin B1 to rohu, Labeo rohita (Hamilton).
AB  - Pathological alterations in various organs of rohu (L. rohita) fingerlings
      following acute (0, 7.50, 11.25 and 13.75 mg/kg body weight) and subchronic (0,
      1.25 and 2.50 mg/kg body weight) single i.p. aflatoxin B1 exposure for 10 and 90
      days, respectively, were investigated. Mortality (dose-dependent) was marked only
      during acute toxicosis. The changes observed in various organs were dose and time
      dependent. The acute dose groups revealed toxic changes viz., necrotic and
      vascular changes in liver and gill lamellae; meningitis, congestion in brain,
      degeneration and inflammatory reaction in heart along with degenerative to
      necrotic changes in kidney tubules and sloughing of the intestinal mucosa. During
      subchronic exposure to this toxin, preneoplastic lesions in liver along with
      changes in spleen, intestine, gill and pancreas were recorded. With low doses of
      aflatoxin, the fish did not reveal any mortality or external signs other than
      catchexia and increased pigmentation on scales. In composite culture practice of
      Indian major carps, this could be of economic significance.

PMID- 11510130
TI  - Influence of lead in soil on mycorrhizal development and plant growth of
      Cyamopsis tetragonoloba (Linn.) Taub.
AB  - Growth of C. tetragonoloba suffered with increase in concentration of Pb in soil.
      Plant biomass declined significantly at concentrations above 60 ppm of Pb. Roots
      showed more pronounced impact as compared to shoots. At highest applied
      concentration of lead (100 ppm), fresh weight of fruits decreased by 33% and dry
      weight by 52% as compared to control. No significant impact was noticed on the
      development of mycorrhiza at lower concentrations (15-45 ppm) of lead
      contamination. At higher concentrations of Pb (60 and 75 ppm), there was a
      decrease in VAM colonization. VAM hyphae had irregular size and terminated
      abruptly in outer cortex of root. Number of VAM fungal spores in rhizosphere also
      decreased with increase in the edaphic Pb concentration.

PMID- 11510131
TI  - Siderophore production by fluorescent pseudomonads colonizing roots of certain
      crop plants.
AB  - Twelve fluorescent Pseudomonas isolates colonizing roots of four crop plants,
      chilli, cotton, groundnut and soybean, were examined for extracellular
      siderophore production in different media under iron deficient conditions. While
      all the organisms produced siderophores, they varied in the quantity of
      siderophores produced and in their preference to the medium. The siderophores
      were invariably hydroxamates (pyoverdine) of trihydroxamate type which formed
      bidentate ligands with Fe III ions.

PMID- 11510132
TI  - Amelioration of NaCl stress in Pisum sativum Linn.
AB  - Activity of endogenous auxins and growth inhibitors, gibberellins and cytokinins
      was observed in the extracts of seedlings of Pisum sativum under NaCl stress.
      After 6 days of germination, when Pisum sativum seedlings were subjected to low
      concentration of NaCl (50 mM) or boron (10 ppm) increased the endogenous growth
      regulating substances. Higher concentration of NaCl (150 mM) decreased endogenous
      level of growth regulators, length of the root and shoot, and fresh and dry
      weights of seedlings, whereas boron increased the parameters except endogenous
      growth regulators. Mitotic index and some abnormalities were observed in the
      treated plants. SDS-PAGE banding pattern of Pisum sativum seedlings extracted in
      tris-glycine and tris-HCl showed that lower concentration of NaCl increased the
      number of protein bands, while the higher concentration decreased these protein
      bands. Combination of boron and NaCl (150 mM) caused an increase in total number
      of protein bands compared with the total number of bands recorded by using NaCl
      (150 mM) alone.

PMID- 11510133
TI  - Effect of ATP sensitive potassium channel modifiers on antinociceptive effect of
      metoclopramide.
AB  - Metoclopramide, a prokinetic drug, has been documented to produce antinociceptive
      response in animal models through opioid pathways. Morphine has been shown to act
      through ATP sensitive potassium channels (KATP) to produce antinociceptive
      response. However, such a possibility has not been examined for metoclopramide.
      The present study investigated this using pharmacological tools. Acetic acid
      induced abdominal constriction assay procedure was utilized to assess
      antinociception. The results confirmed that metoclopramide has antinociceptive
      response. Glibenclamide, a KATP channel blocker, pretreatment antagonized this
      response. Where as, in minoxidil pretreated animals, metoclopramide elicited an
      enhanced antinociceptive response. Glibenclamide and minoxidil, which are known
      KATP channel blocker and opener respectively, interfered with metoclopramide
      antinociception. These finding are suggestive of a role for KATP channels in
      metoclopramide antinociception in mice.

PMID- 11510134
TI  - Modulatory effect of Mentha piperita (Linn.) on serum phosphatases activity in
      Swiss albino mice against gamma irradiation.
AB  - Mentha extract (ME; 1 g/kg body wt) given orally for three consecutive days prior
      to whole body irradiation (8 Gy) showed modulation of activity of serum
      phosphatases in albino mice. Values of acid phosphatase activities were
      significantly higher in untreated irradiated group throughout the experiment.
      Irradiated animals pretreated with ME showed significant decline in acid
      phosphatase activity as compared to untreated irradiated animals at all autopsy
      intervals and attained normalcy at day 5. A marked decrease in serum alkaline
      phosphatase activity was recorded in both irradiated groups. However, in ME
      pretreated irradiated group, values of alkaline phosphatase activity remained
      significantly higher than untreated irradiated animals at all intervals and
      attained normalcy from day 5 onwards.

PMID- 11510135
TI  - A simple and inexpensive "cell dissociation sieve-tissue grinder" apparatus.
AB  - A simple and inexpensive cell dissociation sieve-tissue grinder apparatus
      consisting essentially of stainless steel sieve (the one popularly used for
      sieving tea leaves) and a glass syringe plunger acting as pestle, is described
      for making single cell suspension.

PMID- 11510136
TI  - Induction of antioxidative enzyme by the ayurvedic herb Desmotrichum fimbriatum
      Bl. in mice.
AB  - The herb Desmotrichum fimbriatum Bl. (family: Orchidaceae), sold as Jibanti in
      West Bengal, is used in 'Rasayana therapy' in Ayurveda. Its effect on the
      modulation of the two antioxidant enzymes peroxidase and catalase has been
      studied in mice liver during 'cold water swim' (CWS) stress using appropriate
      controls. The drug, i.e. the aqueous ethanolic extract of the herb (whole plant)
      was found to increase peroxidase titre in the hepatic cells of normal mice. But
      in the stressed group, the drug displayed no effect on the peroxidase content,
      while it elicited an elevation of the catalase content. infinity-Tocoferol was
      used as the standard drug. These data suggested that the drug can ameliorate the
      peroxidative damage caused in mice by CWS stress.

PMID- 11510137
TI  - Effect of cadmium and zinc-metallothionein on methemoglobin and nitric oxide in
      dimethylnitrosamine treated rats.
AB  - Protective effects of metallothionein (MT) have been studied against
      dimethylnitosamine (DMN) toxicity in laboratory rats. MT was induced by feeding
      rats on repeated sublethal doses of cadmium and zinc. These rats were
      subsequently administered DMN. Methemoglobin and nitric oxides, the established
      markers of DMN toxicity, were estimated in the blood samples of MT protected
      rats. Preinduction of MT decreased methemoglobin and ameliorated the generation
      of nitric oxides. Antioxidative effects of MT may have manifested these results,
      however, an effect on N-nitrosation is also speculated.

PMID- 11510138
TI  - Isolation, screening and identification of bacterial strains for degradation of
      predigested distillery wastewater.
AB  - Three bacterial isolates from the activated sludge of a distillery wastewater
      treatment plant identified as Xanthomonas fragariae, Bacillus megaterium and
      Bacillus cereus were found to remove COD and colour from anaerobically digested
      distillery wastewater in the range of 55 to 68% and 38 to 58% respectively.

PMID- 11510139
TI  - Efficacy of ammonia in detoxification of fumonisin contaminated corn.
AB  - Fumonisin B1 level in culture material and in naturally contaminated corn by F.
      moniliforme was reduced by 30 and about 40%, respectively, by ammonia treatment.
      Atmospheric ammoniation of corn did not appear to be an effective method for
      detoxification of F. moniliforme contaminated corn.

PMID- 11510140
TI  - Circular form of regeneration in an unidentified species of land planarians,
      Bipalium sp.
AB  - The communication describes an interesting and possibly novel finding regarding a
      species of land planarians (Bipalium sp.) from a high altitude of Himalayan
      range. The regeneration in Bipalium sp. is highly interesting and the process
      takes about a fortnight for the completion. Accumulation of numerous basophilic
      cells in parenchyma at the blastema region occurs within 5 days after excision
      and in 7 to 9 days the head and tail regions become reorganized with the
      formation of functional pharynx in the tail piece. The neoblast cells in the
      mesenchyme and the gastrodermis cells proliferate continuously replenishing the
      population of stem cell for growth, reproduction, and regeneration. Many
      undifferentiated cells are present even in completely regenerated specimens.
      Sometimes middle piece regenerates apparently fuse at the blastema surface
      forming a peculiar circular form of Bipalium sp. where both the head and tail cut
      ends join completely. These regenerated individuals excepting the middle piece
      regenerate behave in a normal fashion within 12-14 days.

PMID- 11510141
TI  - Antidiabetic activity of a polyherbal preparation (tincture of panchparna) in
      normal and diabetic rats.
AB  - The present work was executed to evaluate the anti-diabetic potency of a
      polyherbal formulation, and its influence on derangement in the metabolism of
      glucose and cholesterol and changes in sodium levels in serum and urine in normal
      and alloxan induced diabetic rats. Serum glucose and serum cholesterol levels
      were found to be increased in diabetic animals. Serum sodium and urinary sodium,
      hepatic glycogen levels are found to be decreased in diabetic state. Treatment
      with the polyherbal formulation (1.0 ml/kg body wt) for 30 days in diabetic
      animals has shown decrease in serum glucose and serum cholesterol levels in
      comparison to control animals, whereas in normal treated animals, the formulation
      does not effect the serum glucose and serum cholesterol levels. Serum sodium and
      urinary sodium levels were increased in both diabetic treated and the control
      animals. Hepatic glycogen levels were increased in diabetic treated animals, but
      there was no change in the control treated animals.

PMID- 11510142
TI  - [All human and animal organs, tissues and cells are endocrine].
AB  - All known hormones are shown to be synthesized and secreted by different
      structures of the brain and nervous system, including neurons and glial cells and
      many of them are neurotransmitters. It should be recognized that all the organs,
      tissues, and cells of animals and man are endocrine and secrete different
      hormones into the intercellular space and blood.

PMID- 11510143
TI  - [Cerebral sleep-wakefulness cycles in humans after psychoemotional stress].

PMID- 11510144
TI  - [Active forms of oxygen and nitrogen in blood cells of patients with rheumatoid
      arthritis: effect of laser therapy].
AB  - Infrared pulse laser therapy was studied for its impact on the production of
      active forms of oxygen and nitrogen by neutrophils from patients with rheumatoid
      arthritis (RA). The authors determined the non-activated and PMA-activated
      production of superoxide anion-radical, peroxynitrite, peripheral neurophilic
      NAD.PH-oxidase and superoxide dismutase activities, and the red blood cell
      concentrations of reduced glutathione. Before therapy, non-activation RA
      neurophilic production of superoxide was much higher than in donors. Laser
      therapy made this parameter normal. Similarly, neutrophilic peroxynitrite
      production (defined by dihydrorhodamine oxidation) in RA patients was 1.7 times
      higher than the normal values. IF-laser therapy decreased peroxynitrite
      production to the values observed in donors. It is important that the therapy
      caused increased SOD activity (that was lower in RA patients prior to therapy) up
      to apparently control values. Thus, IF-laser therapy has a certain antioxidative
      effect by increasing SOD activity in RA patients' blood cells and reducing the
      production of highly reactive oxygen and nitrogen forms.

PMID- 11510145
TI  - [Study of the antiviral activity, pharmacokinetics and toxic properties of
      liposomal form of human alpha-2b interferon administered topically].
AB  - Human liposomal recombinant alpha 2b-interferon topically applied to laboratory
      animals was tested for antiviral activity, pharmacokinetics, and toxicity. The
      interferon was shown to penetrate through the skin and to circulate in the blood
      of experimental animals longer than its injectable form, and to exhibit its
      antiviral activity against genital herpes in guinea pigs. It produced no toxic,
      skin-irritant, or allergic effects in laboratory animals.

PMID- 11510146
TI  - [Development of medical engineering science].

PMID- 11510147
TI  - [Plasminogen activators of urokinase and tissue types and their inhibitor (PAI-1)
      in cytosol fraction in thyroid diseases].
AB  - Enzyme immunoassay (ELISA) was used to estimate the levels of plasminogen
      activators of urokinase (uPA) and tissue (tPA) types and one of their inhibitors
      (PAI-I) in the cytosolic fraction of the thyroid in 129 patients with malignant
      and benign tumors and various non-cancer diseases of the gland. Tumors from
      patients with thyroid cancer displayed the lowest levels of tPA and the highest
      levels of uPA and PAI-I, while those from patients with benign thyroid diseases,
      including adenoma, had high concentrations of tPA and relatively low levels of
      uPA and PAI-I in the tissue of the diseased organ. At the same time, the lowest
      levels of uPA and PAI-I were found in patients suffering from toxic goiter with
      and without adenomatosis. In terms of uPA and PAI-I levels, patients with nodular
      colloidal goiter were intermediate between those with toxic goiter and adenoma,
      on the one hand, and those with thyroid cancer, on the other.

PMID- 11510148
TI  - [Critical state medicine. Surfactant therapy of adult respiratory distress
      syndrome (results of multicenter studies)].
AB  - The paper provides evidence for the pathogenetic approach to treating acute lung
      lesion (ALL) and adult respiratory distress syndrome (ARDS). An algorithm of the
      use of Russian lung surfactant preparations: CT-HL and CT-BL has been developed.
      In involves earlier (the first days following the onset of respiratory failure)
      use of surfactant, its combined bolus intratracheal or intrabronchial
      administration in doses of 200-400 mg/m2, followed by continuous (5-day) aerosol
      inhalation in doses of 20-30 mg/h for children and 30-75 mg/h for adults until
      pronounced clinical and X-ray effects are shown. Fifty three patients were found
      to develop ALL and ARDS in the presence of severe pneumonia, postperfusion lung
      disorders, reperfusion syndrome, pulmonary embolism, long-term artificial
      ventilation, combined car accident injury and gunshot wounds of the chest,
      heroine intoxication, septic shock, sepsis, postoperative sequels in cancer
      patients, and after hepatic transplantation or massive aspiration of gastric
      contents. Fifty patients were overcome their critical status, 44 survived. The
      duration of artificial ventilation (AV) ranged from 1 to 6 days. Earlier use of
      the drugs made it possible to transfer patients to safe AV regimens and to
      eliminate ALL and ARDS rapidly and to significantly reduce mortality due to
      critical states.

PMID- 11510149
TI  - [New biophysical technologies in the early diagnosis of organ pathology].
AB  - Kinetic electropuncture diagnosis (CASKED) is the advancement of Voll's method
      and is characterized by a basically new procedure to apply an electrical signal
      to the acupuncture points (AP). This method records and analyzes not only the
      amplitude of AP potential, but its temporal kinetics (in the range up to 100
      seconds), he characteristic times of kinetic changes are used as diagnostic
      signs. CASKED makes it possible to make a direct diagnosis by taking into account
      the localization and characteristic features of a pathological process and to
      access changes in a patient's condition during treatment.

PMID- 11510150
TI  - [Formation of medical-demographic processes in the Russian Federation].
AB  - The authors analyze the specific features of the present medical and demographic
      situation in the Russian Federation, the naturally research regularities
      determining the evolution and development direction of population processes in
      the 20th century by using the populational advance to the demographic transition
      to the present-day reproduction as an example. Socioeconomic factors affecting
      the demographic structure of society are considered.

PMID- 11510151
TI  - [Atherosclerosis as pathology of polyene fatty acids].

PMID- 11510152
TI  - [Academician A. A. Bogomolets and his school (the 120th anniversary of his
      birthday)].

PMID- 11510153
TI  - [The theory of functional systems and preventive medicine].

PMID- 11510154
TI  - [Problems in surgical treatment of the cicatricial stage of retinopathy of
      prematurity].
AB  - Fifty-one children with stage V retinopathy neonatorum on 2 eyes were operated
      on. The author emphasizes numerous changes in the children and the importance of
      thoroughly examining the lungs, heart, liver, and particularly central nervous
      system by neurosonography. Retinopathy neonatorum is associated with
      characteristic signs of dysgenesis in all ocular tissues, and therefore the term
      "ophthalmopathy neonatorum" is proposed, better describing this condition.
      Surgical treatment of stage V retinopathy neonatorum is recommended in cases with
      bilateral process. The operation helps attain a normal ratio in the anterior
      segment tissues in 97% cases, transparent media in 70%, partial or complete
      adhesion of the retina in 38% cases. Visual functions improved in every 6th-7th
      child (in 14.3%).

PMID- 11510155
TI  - [New method of astigmatism correction: bitoric single-meridian kerato-ablation in
      photorefraction surgery].
AB  - The technique and results of an original method for correction of common myopic
      astigmatism and mixed small-sphere astigmatism by means of bitoric
      photokeratoablation are described. Forty-six operations were performed on
      patients with 2-7 diopter astigmatism. Residual 0.87 diopter astigmatism was
      observed in patients with the initial value of less than 3 diopters. At initial
      astigmatism higher than 3 diopters, residual value was 1.49 diopters 3 months
      postoperation. No changes in the spheric component of initial refraction
      occurred. The proposed technique includes estimation of bitoric keratoablation,
      order of steps, and values of ablation algorithm enhancement. The method helps
      decrease the depth of keratoablation, rules out hypercorrection, and creates
      optimal conditions for reoperations.

PMID- 11510156
TI  - [Vascular network of choroid melanoma as shown by triple ultrasonic examination].
AB  - Twenty-four patients (24 eyes) with choroid melanoma were examined by triplex
      ultrasonic examination (gray-scale scanning in the real time mode, color Doppler
      mapping, and pulse wave dopplerography). All tumors possessed individual vascular
      network with larger vessels with higher bloodflow velocity at the periphery in
      comparison with the center of the tumor. A large feeding vessel growing into the
      tumor at the periphery along the internal (facing the vitreous body) surface of
      the tumor was detected in the overwhelming majority of cases.

PMID- 11510157
TI  - [Characteristics of the structure of the posterior segment of the eye and
      morphology of posterior detachment of the vitreous body depending on the nature
      of pathological process as shown by ultrasonic B-scanning].
AB  - The data of B-scanning of 120 eyes with various diseases are analyzed. The
      authors pay special attention to the morphology of posterior segments of the
      vitreous and posterior hyaloid detachment and to relationship between tissues of
      the posterior segment and the type of pathological process. Sonograms with
      certain nosological entities are described and deciphered.

PMID- 11510158
TI  - [Characteristics of retinal vascular involvement in systemic lupus
      erythematosus].
AB  - Retinal vascular abnormalities were studied in 194 patients with systemic lupus
      erythematosus (SLE). All patients fulfilled the American Rheumatism Association
      criteria for SLE. The mean age of patients was 31.9 +/- 9.7 years (17-63 years),
      women falling ill 5 times more often than men. Retinal vascular abnormalities
      were found in 67 (34.5%) patients and were as follows: retinal angiopathy
      (80.6%), cotton-wool spots (10.4%), occlusion of central vein or its branches
      (3%), occlusion of a retinal artery branch (4.5%), and retinal vasculitis with
      extensive peripheral capillary nonperfusion and neovascularization (3%). In
      general, retinal vascular occlusions were found in 6.7% of all SLE patients and
      in 19.4% of SLE patients with retinal vascular changes. Retinal vascular
      occlusions in SLE patients were associated with the antiphospholipid syndrome.
      Retinopathy did not depend on systemic hypertension or duration of SLE but
      correlated with disease activity. Small retinal vessels were involved more often
      than large vessels (p < 0.0395) and arteries more often than veins (p = 0.0338).
      Visual outcomes were better in patients with cotton-wool spots than in those with
      severe retinal vaso-occlusive disease (0.92 +/- 0.09 and 0.15 +/- 0.13,
      respectively, p < 0.0000).

PMID- 11510159
TI  - [Clinical and immunological characteristics of dystrophic diseases of the retina
      in cleaners up after the Chernobyl AES accident].
AB  - A total of 119 Chernobyl liquidators with dystrophic changes in the retina were
      examined. Primary sclerotic maculodystrophy was diagnosed in 87 (73.1%, 174
      eyes), bilateral peripheral chorioretinal degeneration in 40 (33.6%, 80 eyes),
      and hypertensive retinopathy in 12 patients (10.1%, 24 eyes). Twenty (16.8%)
      patients (40 eyes) presented with combined diseases (maculodystrophy and
      peripheral chorioretinal degeneration, maculodystrophy and retinopathy). Central
      "dry" forms of retinal involvement predominated, affecting mainly central visual
      acuity and electrophysiological parameters. Disordered immunological reactivity
      and activation of autoimmune and immunocomplex reactions play an important role
      in the pathogenesis of these changes.

PMID- 11510160
TI  - [Vision disorders as manifestations of transient ischemic attacks in the
      vertebrobasilar basin].
AB  - Vision disorders caused by ischemia of the cerebral occipital cortex in the
      presence of transitory ischemic attacks in the vertebral basilar basin are
      described. Relationship between complaints of vision disorders and severity and
      frequency of transitory ischemic attacks is analyzed. Exogenous factors provoking
      dysfunctions of visual and vestibular analyzers are discussed. Correlation
      between visual disorders and cerebral hemodynamic disorders and vertebrogenic
      changes in various patterns of transitory ischemic attacks is analyzed. The
      number of complaints of visual analyzer dysfunction is increased by 1/3 in the
      patients with dyscirculatory abnormalities. One of the key symptoms of
      hypofunction of the stem mesencephalic compartments is paralysis or paresis of
      the eyeball convergence, which was recorded in 38% patients.

PMID- 11510161
TI  - [Effects of individual premedication on ocular hemo- and hydrodynamics in
      patients with cataracts].
AB  - Relationship between psychoemotional status of patients and ocular hemo- and
      hydrodynamics has been studied. Individual premedication prescribed with due
      consideration for patient's psychological reactions to preoperative stress
      promoted a decrease of ophthalmic tone and blood filling of ocular vessels.

PMID- 11510162
TI  - [Follow up results and pathogenetic substantiation of the effect of decompression
      surgery on the optic nerve in glaucomatous optic neuropathy].
AB  - Retrospective analysis of the efficiency of optic nerve decompression in
      progressive glaucomatous optic neuropathy in patients with normalized intraocular
      pressure showed widening and/or stabilization of the visual field in remote
      periods (6-11 years) in 83.3% patients. Study of the hemodynamics after optic
      nerve decompression showed a significant improvement of the hemodynamic
      parameters in the orbital artery-central retinal artery system: increased
      bloodflow velocity in the central retinal artery, increase of ophthalmic blood
      pressure and perfusion pressure, dilatation of the arteries, and constriction of
      veins, which indicates improvement of hemoperfusion in the initial portion of the
      optic nerve and retina after decompression surgery on the optic nerve. Extension
      and stabilization of visual field correlated with positive changes in
      circulation.

PMID- 11510163
TI  - [Topographic mapping of retinal function with a scanning laser ophthalmoscope and
      multifocal electroretinography using short M-sequences].
AB  - A new method of multifocal electroretinography making use of scanning laser
      ophthalmoscope with a wavelength of 630 nm (SLO-m-ERG), evoking short spatial
      visual stimuli on the retina, is proposed. Algorithm of presenting the visual
      stimuli and analysis of distribution of local electroretinograms on the surface
      of the retina is based on short m-sequences. Mathematical cross correlation
      analysis shows a three-dimensional distribution of bioelectrical activity of the
      retina in the central visual field. In normal subjects the cone bioelectrical
      activity is the maximum in the macular area (corresponding to the density of cone
      distribution) and absent in the blind spot. The method detects the slightest
      pathological changes in the retina under control of the site of stimulation and
      ophthalmoscopic picture of the fundus oculi. The site of the pathological process
      correlates with the topography of changes in bioelectrical activity of the
      examined retinal area in diseases of the macular area and pigmented retinitis
      detectable by ophthalmoscopy.

PMID- 11510164
TI  - [Fluorescein permeability of the cornea in patients after photorefraction surgery
      in residual myopia following radial keratotomy].
AB  - The barrier function of the cornea was studied before and after eximer laser
      photorefraction keratectomies and laser specialized keratomileusis (LASIK) for
      residual myopia after previous radial keratotomy. The barrier function of the
      cornea was studied by local keratofluoropenetrometry making use of computer
      system for analyzing TV images of the eye. Impaired barrier function of the
      cornea at the site of keratotomic cicatrices did not recover even many years
      after radial keratotomy, while after LASIK it recovered in 2-4 weeks. The time of
      recovery of this function depends on the state of the space between the flaps.
      LASIK does not affect the fluorescein permeability of keratotomic cicatrices.

PMID- 11510165
TI  - [Features of clinical course and proteinase inhibitor balance in tears in eye
      burns of different localization (an experimental study)].
AB  - Chemical burns of the eye of different location (cornea, corneal fragment with
      adjacent conjunctiva, and limbus) were studied in experiments. Clinical picture
      and changes in the lacrimal proteinase inhibitor balance were analyzed. Burn
      disease is less severe and the number of complications is less if a fragment of
      the cornea with adjacent conjunctiva and a fragment of the limbus are injured
      than in case of a corneal burn of the same depth and area. Burn of the total
      limbus area is a severe injury involving essential shifts in the proteinase
      inhibitor balance, leading to deep organic changes in the cornea and inner
      structures of the eye, eventuating in its subatrophy.

PMID- 11510166
TI  - [Closed anterior manual vitrectomy as a method of treatment in vitreal
      complications of intraocular lenses].
AB  - Fifty-five closed anterior manual vitrectomies were carried out in patients with
      vitreal complications after cataract extraction with implantation of posterior
      chamber intraocular lenses. The results indicate high efficiency of anterior
      vitrectomy as a method for surgical treatment of sluggish uveitis, keratopathy,
      macular edema, secondary glaucoma, developing as a result of vitreous prolapse
      during implantation of the posterior-chamber intraocular lens. The operations
      were performed through transscleral and corneolimbic accesses. No cases of
      intraocular lens dislocation occurred.

PMID- 11510167
TI  - [Pathogenetic treatment of central chorioretinal dystrophies with pikamilon].
AB  - Picamilon was used in the treatment of 48 patients with central chorioretinal
      dystrophies. In group 1 (34 eyes) the drug was delivered to the posterior pole of
      the eye through an infusion collagen system, which was followed by He-Ne laser
      exposure. In group 2 (46 eyes) the patients were given picamilon tablets. The
      following examinations were carried out in all patients before and immediately
      after treatment: evaluation of visual acuity, borders of peripheral visual field,
      critical frequency of fusion of flashes, visocontrastometry, electroretinography
      with consideration for pathological changes in the retina, rheography, direct and
      indirect ophthalmoscopy. Electric sensitivity and electric lability of the retina
      were evaluated and the function of the off/on channels examined. Subjective and
      objective parameters improved both in the first and second groups (in 98 and 65%,
      respectively). Picamilon promoted extension of the peripheral borders of visual
      field, improved contrast sensitivity, and increased the velocity of the
      sensorimotor reaction, which indicated improvement of interactions between
      neurons and of receptor function.

PMID- 11510168
TI  - [Ophthalmological manifestations of cavernous sinus thrombosis].
AB  - Thrombosis of cavernous sinus is one of the most grave diseases of cerebral
      venous system; its first signs most often manifest in the organ of vision. Pain
      in the orbit and the respective half of the head develop in the presence of
      general fatigue, chill, and fever. In parallel with this, venous dyscirculatory
      disorders in the eye and its appendages involve all oculomotor nerves in
      succession. Further progress of the disease leads to development of congestive
      optic disk. Involvement of the other eye is one of the most severe complications
      of cavernous sinus thrombosis. Further course and manifestations depend on 3
      factors: premorbid status, location of the focus of infection, and routes of its
      penetration into cavernous sinus.

PMID- 11510169
TI  - [Characteristics of clinical course and treatment of metastatic ophthalmia].

PMID- 11510170
TI  - [Phthiriasis of the eyelids].

PMID- 11510171
TI  - [Leber's hereditary optic neuropathy].

PMID- 11510172
TI  - [Characteristics of morphological and functional state of erythrocytes in
      patients with primary open-angle glaucoma with normalized intraocular pressure].
AB  - Disorders in erythrocyte morphology and function (impairment of erythrocyte
      membranes and decreased erythrocyte deformability), leading to impairment of
      capillary endothelium with release of Willebrand factor into the blood, increase
      of blood viscosity, and disorders in microcirculation and transcapillary exchange
      in the optic disk, were detected in 87.5% of 49 patients (70 eyes) with
      nonstabilized course of primary open-angle glaucoma with normalized intraocular
      pressure. Biochemical analysis of plasma lipids showed atherogenic hyperlipidemia
      with decreased antioxidant activity, which favored the development of these
      changes and was one of the factors determining the clinical course of disease.

PMID- 11510173
TI  - [Method of laser coagulation in the treatment of retinal breaks and detachment.
      State of the art].

PMID- 11510174
TI  - [Excimer laser correction of ametropia in children].

PMID- 11510175
TI  - [Cryokeratoplasty and keratoplasty in the treatment of chronic bullous
      keratopathy].
AB  - Comparative analysis of the results of cryokeratoplasty by the Kasparov
      Gorkiladze method (72 operations) and common perforating keratoplasty (60
      operations) in patients with bullous keratopathy of the third-fourth stages (mean
      period of observation 48 months) demonstrated the advantages of cryokeratoplasy:
      transparent healing of corneal transplant was attained in 69.4 and 50% cases,
      while the incidence of relapses of bullous keratopathy was 8.3 and 23.3%,
      respectively. Cryopexy leads to elimination of defective epithelial cells and
      creation of anti-edema barrier in the corneal limb with bullous keratopathy, thus
      preventing the dissemination of edema per continuatuum to the transplanted donor
      cornea with viable epithelium. This effect promotes transparent healing of the
      transplant and decreases the risk of relapse.

PMID- 11510176
TI  - [Phototherapy for trophic ulcers of the lower extremities].

PMID- 11510177
TI  - [Cardiogenic ischemic strokes: pathogenetic aspects].
AB  - Eighty-three patients with acute ischemic stroke (56 men and 27 women, mean age
      90.1 +/- 10.8 years) were examined in order to elucidate the significance of
      paroxysmal heart rhythm disorders and silent myocardial ischemia and determine
      the pattern of hemorheological changes. Traditional clinical instrumental
      examinations were supplemented by Holter monitoring and measurements of a wide
      spectrum of hemostatic and hemorheological values. Cardiogenic ischemic strokes
      were pathogenetically heterogeneous. Holter monitoring helped detect the
      significance of paroxysmal atrial fibrillation in the pathogenesis of embolic
      cardiogenic stroke. One of the key factors in development of hemodynamic
      cardiogenic stroke was transitory bradyarrhythmia and deterioration of left
      ventricular contractility. Cardiogenic strokes are associated with hemostatic
      activation with predominant changes in the plasma hemostasis, which dictates
      purposeful hemocorrection.

PMID- 11510178
TI  - [Results of simultaneous 24 hour pH and ECG monitoring in patients with
      cardialgias].
AB  - Simultaneous 24-hour pH and ECG monitoring is suggested as a method for
      differential diagnosis of cardialgias. Fifty-four patients were examined,
      complaining of retrosternal and precardial pain, retrosternal burning, heartburn,
      and belching of unknown origin. Four groups were distinguished. Relationships
      between gastroesophageal reflux disease (GERD) and coronary disease were
      evaluated. Reflux in GERD was hypothesized to be the mechanism triggering anginal
      episodes.

PMID- 11510179
TI  - [Left ventricular remodeling in mitral valve defects].
AB  - Left ventricular (LV) structure and function were studied in 199 with mitral
      valve defect before operation and in 88 patients after mitral valve replacement.
      LV structural-geometric shifts precede functional ones and can predict the
      latter. The rate of LV pathological remodeling depends on LV cavity volume and
      myocardial mass. Criteria of developing pathological LV remodeling are supposed
      to be the following: an increase in the myocardial mass index up to 225 g/m2 in
      2H/D > 0.29, up to 175 g/m2 in 2H/D < 0.30; LV cavity dilation to 7 cm in
      diastole and 5 cm in systole.

PMID- 11510180
TI  - [Differential diagnosis of infective endocarditis and fevers of unrelated
      genesis].
AB  - Case histories of 84 patients with fevers lasting from 2 weeks to 6 months and
      suspected infective endocarditis (IE) were analyzed. Infective endocarditis was
      diagnosed in 15 patients. From the viewpoint of IE diagnosis by the DUKE
      criteria, the major criteria possess the highest diagnostic value. Use of only
      minor DUKE criteria gave false-positive results in diagnosis of IE in feverish
      patients with angiitis, hemopoietic diseases, and malignant tumors with remote
      metastases. The diagnosis of IE should be based on the DUKE criteria, clinical
      picture, and data of laboratory tests (pericarditis, shift of the leukocytic
      formula to the left, increased level of circulating immune complexes, high
      erythrocyte sedimentation rate, etc.).

PMID- 11510181
TI  - [Human biological age, cardiovascular system, and its aging rate].
AB  - Mathematical model of biological age of the cardiovascular system was determined
      by multiple linear regression analysis in 100 normal subjects aged 30-74 years on
      the basis of central hemodynamic, microcirculation, and vascular reactivity
      parameters. The rate of cardiovascular aging is decreased in elderly subjects.
      Before 60 years of age the rate of aging is higher in men than in women.

PMID- 11510182
TI  - [Antibodies to phospholipids and the vascular endothelium in nodular
      polyarteritis].
AB  - Clinical significance of antibodies to phospholipids (aPL) and vascular
      endothelium (aVE) was evaluated in 20 patients (9 women and 11 men aged 36 +/-
      10.8 years) with nodular polyarteritis (NP) corresponding to classification
      criteria of the USA Rheumatology College. Antibodies to cardiolipin (aCL) (IgG
      and IgM) and to beta 2-glycoprotein (beta 2-GP1) (IgG) were titered by solid
      phase enzyme immunoassay. Total serum level of aVE (IgG + IgM + IgA) was measured
      by solid-phase enzyme immunoassay using Eahy. 926 endothelial hybrydoma cell
      culture. Anticardiolipin antibodies were detected in 11 (55%) of 20 patients, 3
      of these had IgG aCL, 4 IgM aCL, and 4 both antibody isotypes. Serum titers of
      all aCL were moderate in all cases. No antibodies to beta 2-GP1 were detected in
      any of the patients. Total serum endothelial activity varied from 0 to 89.7% in
      patients with NP. Mean aVE level was 24.45 +/- 21.2%, which was significantly
      higher than in donors (p < 0.001). In 4 (26.7%) of 15 patients with NP total
      level of aVE surpassed the upper threshold normal value. The presence of aCL
      directly correlated with the presence of reticular livedo (r = 0.54, p < 0.05),
      but not with any other clinical laboratory manifestations of the disease,
      including thrombotic complications (deep thrombosis of lower limb veins, stroke,
      myocardial infarction), renal involvement, increased erythrocyte sedimentation
      rate, increased concentrations of von Willebrand factor antigen and C-reactive
      protein, or angiitis activity. Vascular endothelial antibodies directly
      correlated with renal involvement (r = 1.00, p < 0.01), distal gangrene of the
      limb (r = 0.83, p < 0.01), and angiitis activity (r = 0.78, p < 0.001), with high
      level of von Willebrand factor antigen and increased erythrocyte sedimentation
      rate (r = 0.66 and r = 0.64, respectively; p < 0.01), but not with aCL (r = 0.43,
      p > 0.05) of any isotype (aCL IgG r = -0.01; r = 0.34; p < 0.05). All patients
      with aVE had aCL in the serum (aCL IgG in 1, aCL IgG and IgM in 1, and aCL IgM in
      2 patients). The results indicate different significance of a CL and aVE in NP;
      the mechanisms of realization of their pathogenetic potential are still to be
      investigated.

PMID- 11510183
TI  - [Central hemodynamic disorders and rheological red blood cell properties in
      hemorrhagic fever patients with renal syndrome].
AB  - The aim of this study was to detect a relationship between hemodynamic disorders
      in patients with hemorrhagic fever with the renal syndrome (HFRS) and erythrocyte
      aggregability and erythrocyte membrane ATPase activity. A total of 100 patients
      with HFRS of different severity were examined. Central hemodynamic parameters
      were studied: circulating blood volume, minute volume, cardiac index, stroke
      volume, and total peripheral vascular resistance during preoliguria, oliguria,
      and polyuria periods. Blood parameters were studied: percentage of minimum and
      maximum aggregation, disaggregation coefficient, activities of transport
      adenosine triphosphatases (Na, K, and Ca-activated ATPases and Mg-dependent
      ATPase). The main hemodynamic parameters were increased (p < 0.05) during early
      preoliguria and decreased during oliguria; during the polyuria period they again
      corresponded to the hyperkinetic circulation. The minimum erythrocyte aggregation
      increased by 110 and 130% in medium-severe and severe HFRS, respectively, the
      maximum erythrocyte aggregation by 20 and 28%, respectively (p < 0.05).
      Disaggregation coefficient decreased by 55%. The activities of Na, K(+)-ATPases
      decreased by 13% during preoliguria period, by 17.5% during oliguria, and by
      11.7% during polyuria (p < 0.05) in patients with moderate disease. In severe
      disease these decreases were 14, 19, and 15%, respectively (p < 0.05). Similar
      changes were observed in the activities of Ca(++)-ATPase and Mg-dependent ATPase.
      Hence, the detected hemodynamic changes in patients with medium-severe and severe
      HFRS correlated with disorders in erythrocyte aggregability and decreased
      activity of transport ATPases, which can be used for evaluation of the severity
      of clinical condition and early diagnosis.

PMID- 11510185
TI  - [Dilated cardiomyopathy: present views of its etiology and pathogenesis].

PMID- 11510184
TI  - [Clinical features, personality changes and anti-oxidative system activity in
      patients with peptic ulcer].
AB  - Examination of 54 patients with duodenal peptic ulcer revealed significant
      correlations between the psychological traits of the patients and their plasma
      antioxidative activity in the mild and moderate courses of the disease. There
      were no correlations in patients with severe duodenal peptic ulcer. A correlation
      analysis of the correlation between the personality traits and plasma
      antioxidative activity in patients with peptic ulcer may be used to for its
      prognosis.

PMID- 11510186
TI  - [The course of peptic ulcer in relation to patients' constitution].
AB  - Sixty one patients with peptic ulcer (PU) were examined to assess the specific
      features of its condition in relation to their affiliation to the type of
      morphological constitution (diathesis). Patients with PU were found to have most
      commonly dyscrasic diathesis. With predominant dyscrasic diathesis, there were
      more frequently complications of PU (rough scarring deformations of the gastric
      or duodenal walls, ulcer bleeding, perforation without clear association with the
      advance of PU, patient compliance, and the adequacy of antiulcerous therapy.
      Arthritic diathesis was next to dyscrasic one in its prevalence. Other diatheses
      (tuberculinic, psoriatic) were encountered much less frequently. Analysis of the
      diatheses manifested in a patient allows one to predict the course of PU, which
      is determined not only by the activity and duration of conventional antiulcerous
      treatment, as evidenced by these studies.

PMID- 11510187
TI  - [Immunological features of renal lesion in chronic alcoholism].
AB  - One hundred and sixty males whose mean age was 42 years were examined. Of them
      there were 122 patients with stage II chronic alcoholism (CA), 92 with renal
      lesion following the type of chronic glomerulonephritis (CG) (Group 1); 30
      patients with CA without renal lesion (Group 2), and 42 patients had CG alone
      (Group 3). Methods that characterize humoral immunity were used. These included
      detection of circulating immune complexes (CIC) by polyethylene glycol
      precipitation, measurement of the concentrations of IgA, IgM, and IgG by the
      Mancini radial immunodiffusion assay, detection DNA antibodies by the Farre test
      modified by V. V. Koshelev, that of serum anticomplement activity, measurement of
      the levels of complement by its hemolytic activity, determination of the activity
      of the lysosomal enzymes acid RNAase, acid DNAase, and cathepsin by the procedure
      of A. A. Pokrovsky et al. Complex estimation of the content of CIC,
      immunoglobulins, DNA antibodies and the activity of the lysosomal enzymes in
      patients with renal lesion makes it possible to evaluate the severity of a
      pathological process and to make its prognosis.

PMID- 11510188
TI  - [Omeprazole and misoprostol for NSAID-induced gastropathies: comparative
      efficiency of their short-term treatment].
AB  - It is rather difficult to choose a drug to treat nonsteroidal anti-inflammatory
      drug (NSAID)-induced gastropathies in patients with rheumatic diseases, which
      primarily makes it necessary to use antiulcerous treatment as part of continuous
      NSAID therapy. Detecting upper gastric ulcers or erosions in many patients
      admitted to a rheumatology hospital for exacerbation of the underlying disease
      cannot cause NSAID to be discontinued even temporarily as this may lead to a
      significant deterioration and progression of the joint syndrome. The aim of the
      study was to evaluate the efficiency of 2-week treatment with misoprostol
      (Cytotec), 800 micrograms/day, and omeprasole (Omez), 40 mg/day, for NSAID
      induced gastropathy in 63 patients with rheumatic diseases. The study has
      indicated that the use of Omez seems to be more advisable than that of Cytotec in
      the treatment of NSAID-induced gastropathy if it is necessary to continue to
      treat the patient with a whole range of antirheumatic drugs. Equally effective in
      healing ulcers and erosions, Omez is much better tolerated and able to rapidly
      relieve gastralgias and dyspepsia. It seems that the use of Cytotec for NSAID
      induced gastropathy with a great deal of side effects and relatively less
      efficiency borne in mind may be limited because of cases of inefficiency of
      proton pump inhibitors.

PMID- 11510189
TI  - [Evaluation of the efficacy of isosorbide-5-mononitrate in CHF patients
      unresponsive to isosorbide dinitrate therapy].
AB  - The purpose of this study was to evaluate the antianginal and antiischemic
      effects of isosorbide-5-mononitrate (Mono Mack) in patents unresponsive to its
      therapy. Thirty eight patients aged 38 to 70 years who had coronary heart disease
      (CHD) were followed up. Estimation of the number of daily anginal episodes, 24
      hour monitoring, EchoCG, bicycle ergometry, tetrapolar rheocardiography, and self
      assessment were made. Prior to the follow-up all the patients were treated with
      nitrosorbide (80-100 mg/day), beta-blockers, ACE inhibitors, disaggregants, and a
      complex of physico- and psychotherapies. CHD progression was an indication for
      the use Mono Mack. Its dose was 20 mg twice a day. Following 18-20 days, the
      efficiency of its use was evaluated. The treatment yielded a clinical effect in
      all the patients. The total daily number of anginal episodes decreased from 3.9
      to 1.2 times. 24-hour monitoring showed an average decrease in the duration of ST
      segment depression from 554 to 245 min a day. There was a significant increase in
      the patients' physical fitness and a trend for cardiac contractility to increase.
      They felt all better. With clinical improvement, 5 patients had no changes, as
      evidenced by instrumental studies. It is concluded that Mono Mack is highly
      effective with dinitrate tolerance, 1.8-fold decrease in the dose of nitrates,
      and good interaction with other drugs.

PMID- 11510190
TI  - [Experience with meloxicam treatment of ankylosing spondylarthritis].

PMID- 11510191
TI  - [Diagnosis of pancreatic diseases: past, present and future].

PMID- 11510192
TI  - [Problems in diagnosing intestinal amebiasis].

PMID- 11510193
TI  - [Respiratory syndrome masking lymphogranulomatosis].

PMID- 11510194
TI  - [Schonlein's purpura in a 85 year old woman with severe gastrointestinal
      lesions].

PMID- 11510195
TI  - [Evolving hemolytic anemia in the presence of senile calcified aortic stenosis].

PMID- 11510196
TI  - [A gastroenterologist's choice: proton pump inhibitors of H2 histamine receptor
      blockers in the treatment of peptic ulcer].

PMID- 11510197
TI  - [Assessing the surgical risk in patients with concomitant cardiovascular
      diseases].

PMID- 11510198
TI  - [Diet, smoking and reproductive history as risk factor for cervical cancer].
AB  - BACKGROUND: Epidemiological studies have suggested that smoking, nutrition and
      sexual patterns are major risk factors for cervical cancer. AIM: To study the
      association between food consumption patterns, smoking and sexual behavior and
      the risk of cervical cancer. MATERIAL AND METHODS: A matched case control study
      of 170 cases and 340 controls. Food and nutrient intakes were assessed by a food
      frequency questionnaire considering 58 antioxidant rich food items. Median daily
      intake of vegetables, fruits, antioxidant vitamins and fiber was calculated. A
      conditional logistic regression model was used to determine odds ratios
      associated with variations in nutritional intake and no nutritional factors (age
      at first delivery, parity, body mass index, family history of cancer and
      smoking). RESULTS: High intakes of vegetables, fruits, beta carotene, vitamin C,
      E and fiber were associated with a lower risk of cervical cancer (Odds ratios
      ranging from 0.56 to 0.78). The risk for cancer was inversely associated with the
      age at first delivery and directly associated with the total number of
      pregnancies and smoking. Multivariate analysis model showed a protective effect
      for vegetable and vitamin E consumption (odds ratio of 0.6 with confidence
      intervals of 0.5 to 0.8 p < 0.001) and a higher risk associated to smoking (odds
      ratio 2.8, confidence intervals 1.5-5.5 p < 0.002) and a younger age at the first
      delivery (odds ratio 3.37 confidence intervals 2-5.3 p < 0.001). CONCLUSIONS:
      Cervical cancer is associated with reproductive and food consumption behaviors. A
      higher intake of vegetables and foods rich in vitamin E can reduce its risk.

PMID- 11510199
TI  - [The classification of coronary lesion from Society for Cardiac Angiography and
      Intervention predicts better results of coronary angioplasty than the one from
      American College of Cardiology/American Heart Association Coronary Disease].
AB  - BACKGROUND: The classification of coronary lesion complexity, using the American
      College of Cardiology/American Heart Association (ACC/AHA) is a predictor of
      balloon angioplasty success. Stents have improved results even in complex
      lesions. AIM: To compare the ACC/AHA and the new Society for Cardiac Angiography
      (SCA&I) coronary lesion scores as predictors of angioplasty success. PATIENTS AND
      METHODS: Ali consecutive angioplasty procedures (n = 346, 456 lesions, 47%
      stents) were prospectively analyzed from August 1996 to March 1999. Coronary
      lesions were classified using the ACC/AHA and SCA&I scores. Angiographic success
      was assessed and its multivariate predictors determined with logistic regression
      analysis. RESULTS: According to the ACC/AHA score, angiographic success was 97,
      92.7, 93.3, and 82.3% in A, Bl, B2 and C lesions respectively (p = 0.013). There
      only were significant differences in success between C and A, Bl or B2 lesions.
      According to the SCA&I score success was achieved in 97.3, 97.9, 75.8 and 33.3%
      in nonCP, CP, nonCO and CO lesions respectively (P < 0.001). With the SCA&I score
      statistically significant differences in angiographic success were found for all
      lesion score comparisons, except between nonCP and CP lesions. No other variables
      had predictive value for angiographic success. CONCLUSIONS: Coronary angioplasty
      angiographic success is better predicted by the new SCA&l lesion score than with
      the ACC/AHA lesion classification in a group of patients with frequent use of
      stents.

PMID- 11510200
TI  - [Auto-antibody profile and breast feeding in type 1 diabetic patients].
AB  - BACKGROUND: Islet cell-specific autoantibodies such as islet cell antibody (ICA),
      antiinsulin (IAA), anti-glutamic acid decarboxylase (GAD) and anti-tyrosine
      phosphatase (IA2) can be present in patients with type I diabetes. Breast feeding
      duration and the early exposure to milk substitutes are environmental factors
      associated to etiology of type 1 diabetes. AIM: To study the frequency of the
      anti-GAD, anti-IA-2 e ICA antibodies in Chilean type 1 diabetic patients and
      determine the possible modulator effect of the breast feeding. PATIENTS AND
      METHODS: One hundred thirty four type 1 diabetic patients, aged one to 15 years
      old, were studied at the moment of their diagnosis. Patients were classified
      according to the duration of exclusive breast feeding. IA-2 and GAD were
      determined by radio immuno assay and ICA by means of indirect immunofluorescence.
      RESULTS: Subjects with three months or less and those with more than three months
      of breast feeding were positive for ICA in 78.8 and 90.6% of cases respectively,
      for GAD in 75 and 54.6% of cases respectively (p = 0.024) and for IA-2 in 73 and
      43.8% of cases respectively (p = 0.001). All three antibodies were positive in
      53.9 and 21.8% of children with less or more than three months of breast feeding
      (p = 0.001). CONCLUSION: Both IA-2 and GAD antibodies are less frequently
      positive in type 1 diabetic patients who have been breast fed for more than three
      months. These findings suggest a possible attenuating role of exclusive breast
      feeding on pancreatic aggression events in patients with type 1 diabetes.

PMID- 11510201
TI  - [Diagnosis of Clostridium difficile diarrhea: in search of a more efficient
      clinical focus].
AB  - BACKGROUND: The clinical parameters for the suspicion of Clostridium difficile
      infections, namely the use of antimicrobials and diarrhea, have a low predictive
      value for the diagnosis. AIM: To search other clinical variables and determine a
      clinical prediction model for (Clostridium difficile diarrhea. PATIENTS AND
      METHODS: All patients to whom a Clostridium difficile study was requested, were
      prospectively studied during 5 months. Clinical variables of these patients were
      registered. The diagnosis of Clostridium difficile was done using the
      cytotoxicity test in fibroblast cultures. RESULTS: Ninety two patients were
      analyzed and in 26, the diagnosis of Clostridium difficile was confirmed. A
      logistic regression model disclosed an age over 60 years old, the presence of
      mucus in the stools and a temperature over 37.8 degrees C in the previous 24 h,
      as significant predictors of the infection. The correlation of the model, between
      the predicted probability and the observed condition, was 81.5%. CONCLUSIONS: The
      presence of the clinical variables identified in this study are associated with a
      high probability of an infection by Clostridium difficile in patients with
      diarrhea and the recent use of antimicrobials.

PMID- 11510202
TI  - [Clinical and psychometric diagnosis of depression in patients in general
      medicine].
AB  - BACKGROUND: The Hamilton scale, applied by an external evaluator and the self
      rating Beck inventory for depression, can give discrepant results in psychiatric
      patients with depression. AIM: To compare depression scores obtained with the
      Hamilton scale and the Beck inventory in general medical patients. PATIENTS AND
      METHODS: Patients attending an outpatient clinic of a University Hospital were
      studied. Clinical psychiatric diagnoses were based on DSM-III. Hamilton scale was
      applied to 100 patients and 80 answered the Beck depression inventory. RESULTS:
      Patients with major depression obtained the higher scores with both scales.
      However, Beck inventory had false positive and false negative results. Moreover,
      some patients overstated their depressive symptoms. CONCLUSIONS: Self assessment
      of depression can be distorted by anxiety and somatic symptoms.

PMID- 11510203
TI  - [Clinical significance and frequency of the 11q23/MLL genetic molecular
      alteration in Chilean infants with acute leukemia].
AB  - BACKGROUND: Acute leukemia (AL) in infants generally shows distinctive biologic
      features and has a poor prognosis. AIM: To study the frequency of the cytogenetic
      alteration of 11q23 chromosome or the recombination of MLL gene in infants less
      than 18 months old, with acute leukemia. PATIENTS AND METHODS: We analyzed 37
      cases of AL in infants less than 18 months of age diagnosed in Chile from 1989 to
      1999. The clinical features and cytogenetic/molecular defects of 11q23MLL gene
      rearrangement and their influence in prognosis were determined. RESULTS: There
      were 18 cases of acute Lymphoblastic leukemia (ALL) characterized by female sex
      (67%) high presenting leukocyte count (median 99 x 109/L), blast cells with a
      CD10 negative phenotype (50%) and 11q23/MLL rearrangement (39%). Molecular
      abnormalities of 11q23 were significantly associated with adverse prognosis, with
      an event free survival (EFS) of only 14 +/- 12%. Interestingly, infants with germ
      line 11q23 had a very good outcome with an EFS of 73 +/- 11% (p < 0.025). There
      were 19 cases of acute myeloblastic leukemia (AML) characterized by male sex
      (63%) high leukocyte count (median 93 x 109/L), FAB-MS morphology (53%) and
      11q23/MLL rearrangement (53%). EFS was very poor, 20 +/- 9% and 33 +/- 4% for
      rearranged and germinal group respectively (p = NS), due to a high mortality rate
      during the first month of diagnosis. CONCLUSIONS: These findings demonstrate that
      Chilean ALL infants with 11q23 abnormalities have a very poor prognosis. However
      those with germinal state can enjoy a prolonged disease free survival with the
      current treatment protocols.

PMID- 11510204
TI  - [In vitro antimicrobial susceptibility of Helicobacter pylori strains: isolation
      of strains resistant to clarithromycin].
AB  - BACKGROUND: Our laboratory has carried out an epidemiological surveillance of
      Helicobacter pylori antimicrobial susceptibility since 1997. AIM: To report the
      antimicrobial susceptibility of H pylori strains, isolated in Chile from August
      1997 to August 2000. MATERIAL AND METHODS: Ninety one H pylori strains, obtained
      from antral gastric biopsies during upper gastrointestinal endoscopies were
      studied. Susceptibility towards clarithromycin, amoxicillin, bismuth subcitrate
      and metronidazole was studied by an agar diffusion technique. RESULTS: All
      strains were susceptible to amoxicillin and two strains were resistant to
      clarithromycin. Forty two percent of strains were resistant to metronidazole and
      13% were resistant to bismuth subcitrate. CONCLUSIONS: These results underscore
      the need to maintain an epidemiological surveillance of H pylori antimicrobial
      susceptibility, to modify its eradication therapy accordingly.

PMID- 11510206
TI  - [Characteristics of hospitalization of patients with rheumatic diseases admitted
      to a tertiary care hospital].
AB  - BACKGROUND: The diagnostic profile of patients with rheumatic diseases admitted
      to a general hospital is variable. AIM: To report the epidemiological profile of
      patients with rheumatic diseases admitted to a tertiary care hospital. MATERIAL
      AND METHODS: All admissions to a Medicine ward of a general hospital and seen by
      the Rheumatology team were prospectively registered during one year in 1999.
      Patients were classified as primarily admitted for a rheumatic disease or
      admitted for other cause that required a consultation with the Rheumatology team.
      RESULTS: One hundred forty five admissions due to rheumatic diseases were
      registered. Of these, 82 were due to primary rheumatic diseases. Systemic lupus
      erythematosus, rheumatoid arthritis and vasculitis were the main diagnoses and
      the mean hospital stay was 18.5 days. Sixty three patients required a
      consultation with the Rheumatology team specially due to osteoarthritis and
      crystal induced diseases. CONCLUSIONS: Admissions due to rheumatic diseases are
      prolonged, correspond to 0.46% of all admissions and the main responsible disease
      is systemic lupus erythematosus.

PMID- 11510205
TI  - [Self medication among patients with musculoskeletal symptoms in Araucania
      region].
AB  - BACKGROUND: Self-medication is a common behavior in the general population,
      specially among those suffering from chronic pain. AIM: To study the prevalence
      and characteristics of self medication. SUBJECTS AND METHODS: Aiming to know the
      prevalence and features of self medication, a structured interview was applied to
      272 out of 419 individuals from the general population, that reported
      musculoskeletal symptoms. RESULTS: Sixty five percent of those interviewed
      recognised self medication. No gender differences were observed and there was a
      trend towards a higher frequency of self medication among older individuals. The
      frequency of self-medication was higher in low socioeconomic groups, subjects
      with long lasting pain, those with more severe pain and among subjects with a
      previous prescription. The drugs more frequently used were dipyrone, piroxicam
      and aspirin. The average daily piroxicam dose reported was 27 mg. Self medication
      was not associated with the labor condition of the subjects or the time of
      occurrence of symptoms. CONCLUSIONS: Self medication is a frequent behavior,
      particularly among low socio-economic groups and those with long lasting and more
      severe pain.

PMID- 11510207
TI  - [Acute iron poisoning. A case report].
AB  - The ingestion of iron-containing products is a potential toxicological emergency.
      It is a leading cause of pediatric unintentional ingestion fatalities because
      some iron-containing compounds are readily available (vitamin mixtures, iron
      pills). Among adults, it has been described as accidental overdoses (mainly in
      pregnancy) and as suicidal attempts. We report a 42 years old woman, admitted due
      to the intentional ingestion of iron pills with suicidal purposes. A plain
      abdominal X ray showed at least 20 pills in the gastric fundus and antrum. She
      was successfully treated with intravenous desferroxamine chelation. Plain
      abdominal X ray examination can be very useful in the diagnosis of acute iron
      poisoning.

PMID- 11510208
TI  - [Mammary carcinoma ine ectopic breast tissue. A case report].
AB  - Ectopic breast tissue, that includes supernumerary breasts and aberrant breast
      tissue, develops along the mammary line. Malignancies rarely develop in this
      tissue. We report a 44 years old female subjected to a resection of a 3 cm O
      tumor located 2 cm below the right lower mammary sulcus. The pathological study
      reported an infiltrating ductal carcinoma. The patient was operated again and a
      metastatic carcinoma was detected in three resected axillary lymph nodes.
      Adjuvant chemotherapy and radiotherapy was indicated.

PMID- 11510209
TI  - [Familial gout and nephropathy in a young woman. Report of one case].
AB  - We report a 29 years old woman with a chronic tophaceous gout, whose disease
      started at the age of 18. On clinical examination, the blood pressure was
      elevated. The laboratory assessment showed a serum uric acid of 15 mg/dl, a
      urinary uric acid of 155 mg/24 h, a creatinine clearance of 59 ml/min/1.73 m2 and
      a uric acid excretion fraction off 1.3% (normal 7 to 12%). The clinical and
      laboratory features of this patient suggest the diagnosis of a familial juvenile
      gouty nephropathy.

PMID- 11510210
TI  - [Glucotoxicity and lipotoxicity: factors in the pathogenesis and evolution of
      type 2 diabetes].
AB  - Glucose toxicity refers to the structural and functional damage in the beta cells
      and target tissues of insulin, caused by chronic hyperglycemia. These alterations
      cause a lower hormonal secretion and action (insulin resistance). Lipid toxicity
      refers to the damage caused by persistently high free fatty acid levels, as a
      consequence of triacylglycerol catabolism. Since elevated glucose and lipid
      levels cause a similar damage and interact, the term glucose and lipid toxicity
      refers to their additive effects. This toxicity can be implicated in the
      pathogenesis of type II diabetes and in the secondary failure of oral
      hypoglycemic drugs, leading to the requirement of insulin treatment. Insulin
      resistance with normal glucose levels, glucose intolerance and clinical diabetes
      are the three recognized stages in the development of type 2 diabetes.
      Considering that the first two stages are reversible, a good metabolic control to
      avoid glucose and lipid toxicity could revert or avoid the development of
      clinical diabetes.

PMID- 11510211
TI  - [Ethical aspects of biomedical research. frequent concepts in written norms].
AB  - Most codes and declarations pertaining to the ethics of research involving human
      subjects have been formulated in response to specific events mostly of a painful
      or embarrassing nature. Several concepts appearing repeatedly in their texts are
      highlighted in this paper: principles of respect for persons, beneficence and
      justice, vulnerability and research propriety. Along with some comments on
      current revisions of many international guidelines and the role of bioethics
      committees, a plea is made to have a proactive rather than a reactive stance in
      ethical regulation of biomedical research.

PMID- 11510212
TI  - ["To Milena" (A essay of narrative medicine)].
AB  - Narrative medicine is becoming an increasingly popular way of communicating
      medical problems. This a letter that the author sends to a recently deceased
      patient. He describes his apprehensions on the use of invasive forms of diagnosis
      or treatments and the use of repeated hospital admissions in the context of a
      chronic and progressive disease. He also discusses the use of methods to
      "accelerate" death in suffering patients. He finally describes the dignity of his
      patient to face a chronic and debilitating condition.

PMID- 11510213
TI  - [Inspiratory muscles strength in heart failure and in chronic obstructive lung
      disease].

PMID- 11510214
TI  - [Adverse effect of 3,5,3 triiodothyroacetic acid in the treatment of obesity].

PMID- 11510216
TI  - Structural change of mesoporous silica with sonochemically prepared gold
      nanoparticles in its pores.
AB  - Ultrasonic irradiation of mesoporous silica soaked in a mixture of chloroauric
      acid and isopropanol for 120 min in Ar atmosphere at room temperature yielded
      Au/SiO2 mesoporous composite, which was characterized by high resolution
      transmission electron microscopy and optical absorption measurement. The
      structure of mesoporous silica after sonochemical preparation of gold (Au)
      nanoparticles within its pores was studied by nitrogen adsorption technique. It
      has been shown that the structural parameters, such as specific surface area
      (SSA), porosity (P), the mean pore diameter (lp) were increased significantly
      after ultrasonic irradiation. It is suggested that the collision of Au
      nanoparticles with pore walls and localized erosion induced by the asymmetric
      implosive collapse of cavities on the extensive liquid-solid interface that are
      responsible for the structural change in the mesoporous solid.

PMID- 11510215
TI  - A novel method for the preparation of III-V semiconductors: sonochemical
      synthesis of InP nanocrystals.
AB  - A novel method for the preparation of III-V semiconductor has been provided in
      this paper. At room temperature, InP nanocrystals with diameter of approximately
      9 nm were successfully obtained under high-intensity ultrasonic irradiation for 4
      h from the reaction of InCl(3).4H2O, yellow phosphorus and KBH4 in the mixed
      solvents of ethanol and benzene. Changing some parameters can effectively control
      the size of the products and possible explanations were offered. The products
      were characterized by X-ray powder diffraction, transmission electron microscope
      and electron diffraction pattern. The ultrasonic irradiation and the solvents are
      both important in the formation of the product.

PMID- 11510217
TI  - Intensification of leaching process by dual-frequency ultrasound.
AB  - Ultrasound is gaining importance in metal extraction process. In the previous
      laboratory scale investigation the authors have established the positive
      influence of ultrasound on copper recovery from oxide ores of Malanjkhand, Madhya
      Pradesh, India in an ammonical media. The process parameters in a conventional
      agitation method were optimized and a maximum recovery of approximately 32% in 20
      min was obtained without sonication. The recovery was increased to approximately
      78% by the application of ultrasound over the same period with several advantages
      like decrease in leaching time and the reagent consumption. In the present study
      the leaching process is intensified by studying the metal recovery variation at
      different ultrasonic frequencies (20, 40, 43 and 720 kHz) and intensities (up to
      8 W cm-2) with sonication time. The results show that sinusoidal ultrasound even
      at larger intensity has some limitations with single frequency. However,
      simultaneous application of dual frequency 20 and 40 kHz ultrasound enhanced
      extraction rates along with increased yield. While conventional single frequency
      exposure at either one of the two frequencies at the same acoustic power level
      did not yield similar results, application of two wave sources, as used in the
      study revealed that it is possible to save energy through lowering of time of
      operation process.

PMID- 11510218
TI  - Ultrasound-assisted extraction of ginseng saponins from ginseng roots and
      cultured ginseng cells.
AB  - Ultrasound-assisted extraction was evaluated as a simpler and more effective
      alternative to conventional extraction methods for the isolation of ginsenosides
      (saponins) from various types of ginseng. The ginseng samples were extracted with
      different solvents, under either direct sonication by an ultrasound probe horn or
      indirect sonication in an ultrasound cleaning bath. The ultrasonic extraction was
      compared with the conventional method of refluxing boiling solvents in a soxhlet
      extractor, on the yields of both the total saponin isolated by thin-layer
      chromatography and the individual ginsenosides by high performance liquid
      chromatography. It was found that the sonication-assisted extraction of ginseng
      saponins was about three times faster than the traditional extraction method. The
      ultrasonic extraction was not only more efficient but also convenient for the
      recovery and purification of the active ingredients of plant materials. In
      addition, the sonication-assisted extraction can be carried out at lower
      temperatures which are favorable for the thermally unstable compounds.

PMID- 11510220
TI  - Kinetics of hydrazinium nitrate decomposition in nitric acid solutions under the
      effect of power ultrasound.
AB  - The effect of ultrasound (f = 20 kHz) on the decomposition of hydrazinium nitrate
      was investigated in a nitric acid medium. The kinetics of N2H5+ decomposition and
      initial HN3 formation increase in a linear manner with the HNO3 concentration
      (from 1 to 6 M) and with the ultrasonic intensity (from 0.5 to 3.1 W cm-2). Both
      rates were equal to that of HNO2 formation in the absence of N2H5+, indicating
      that the N2H5+ decomposition mechanism is the same as observed without ultrasound
      between HNO2 and N2H5+. The variation of the steady-state HN3 concentration with
      the HNO3 concentration and the ultrasonic intensity suggests the existence of a
      nonexplosive HN3 thermal decomposition mechanism in the cavitation bubble under
      the effect of ultrasound. It was also observed at ultrasonic intensities
      exceeding 3.5 W cm-2 that the decomposition of HN3 led to the accumulation of
      NH4+ in solution.

PMID- 11510219
TI  - Aqueous sonolytic decomposition of polycyclic aromatic hydrocarbons in the
      presence of additional dissolved species.
AB  - Sonochemical degradation of aqueous polycyclic aromatic hydrocarbons (PAHs)
      results in a first-order loss of the PAHs (k = 0.010-0.027 s-1). When sonication
      occurred in the presence of other organic compounds, the degradation rate
      constant was reduced quite dramatically. This reduction is believed to come about
      through scavenging of radicals by the matrix chemical. When oxygen was bubbled
      into the PAH solution before sonication, the degradation rate constant was
      elevated. Nitrogen purging resulted in decreased rate constants. These results
      indicate that oxygen was an important precursor in the degradation of the PAHs.
      Organic compounds, including humic acid, benzoic acid, and sodium dodecyl
      sulfate, decreased PAH degradation rate constants by scavenging oxygen derived
      reactive transients.

PMID- 11510221
TI  - Monomerization of photosensitizers by ultrasound irradiation in surfactant
      micellar solutions.
AB  - The absorption and fluorescence properties of pheophorbide-a, Sodium salt of
      pheophorbide-a and its long chain (C20H39) ester (Pheophytine) were investigated
      in air-saturated micellar aqueous solutions before and after ultrasound
      irradiation (48 kHz, 10 min). The absorption spectra changed depending on the
      surfactant; cetyltrimethyl ammonium bromide (CTAB) or sodium dodecyl sulfate
      concentrations. The formation of different molecular species in various micellar
      solutions was estimated from the analysis of the absorption spectra. The
      absorption bands resulted from an aggregated form of the chromophore present in
      50 mM phosphate buffer and in pre-micellar solutions. The specific bands of the
      aggregate disappeared with a simultaneous increase of the bands of monomer in
      normal micellar solution. The fluorescence spectra, the lifetimes and the
      fraction of each component (with a characteristic lifetime) of the chromophore in
      the micellar solutions changed significantly before and after ultrasound
      irradiation although the changes in absorption spectra were small. The
      fluorescence emission band at 710 nm due to the aggregate almost disappeared in
      the pre-micellar solution after ultrasound irradiation. The fraction of the short
      lifetime component estimated for the aggregates decreased 55% in H2O or 85% in 2
      mM CTAB, however the long-lifetime components increased after the ultrasound
      treatment. From these fluorescence properties, it was concluded that the
      aggregated molecules were converted to a stable monomeric form by ultrasound.
      Extrapolation of these data to in vivo situations suggests that pretreatment of
      certain photosensitizers with ultrasound in micellar solutions may lead to
      increased efficiency of photodynamic therapy since only the monomers are
      photodynamically active.

PMID- 11510222
TI  - Effect of ultrasound on the dissolution kinetics of phosphate rock in HNO3.
AB  - Ultrasound is known to enhance solid/liquid reactions. This paper deals with the
      investigation of the dissolution of phosphate rock in nitric acid, in the absence
      and presence of ultrasound. The reaction is first-order with respect to H+ and
      activation energy equal to 16 kJ/mol in both cases. The effect of ultrasound is
      on the pre-exponential factor A. An empirical relation is given, which relates
      rate constant to ultrasound power.

PMID- 11510223
TI  - Ultrasonic soldering in electronics.
AB  - Ultrasonic (US) soldering of electronic components, as an alternative to flux
      soldering, is environmentally friendly, improves the quality of soldered
      connections at the mounting elements after long-term storage, and allows the use
      of lead-free solders. Methods of US solder melt activation, lead-free solders in
      US soldering and glass-ceramic capacitor metallization processes have been
      investigated.

PMID- 11510224
TI  - [The effect of pregnancy on the long-term renal function in lupus nephritis
      patients].
AB  - Pregnancy is an important consideration in the treatment of patients with lupus
      nephritis(LN), particularly because the disease predominantly affects females of
      childbearing age. Forty-two patients were studied retrospectively to investigate
      whether delivery adversely affects the natural course of renal function in
      patients with LN. The patients were divided into two groups(patients with
      delivery during the follow-up period: Group I, n = 11; patients who were not
      pregnant: Group II, n = 28; excluding 3 patients with abortion). Group I and II
      profiles at the beginning of the follow-up were as follows: age(years): 26.7 +/-
      5.0(mean +/- SD) and 30.5 +/- 8.4; S-Cr(mg/dl): 0.86 +/- 0.27 and 1.05 +/- 0.52,
      respectively; urinary protein(g/day): 2.42 +/- 3.05 and 3.37 +/- 4.08; follow-up
      period(months): 144 +/- 65.2 and 98.7 +/- 68.0; WHO IV LN was 27%(3/11) in Group
      I and 61%(17/28) in Group II. The activity of SLE in Group I disappeared before
      gestation, except for one case, and no patients experienced recurrence during
      pregnancy or after delivery. Delivery did not adversely affect the long-term
      prognosis of renal function in the three patients with WHO IV LN in Group I. The
      changes in the renal function between Groups I and II during the follow-up period
      were not significantly different (delta 1/Cr/dl/mg/months: -0.00066 +/- 0.00356
      in Group I, 0.00636 +/- 0.02889 in Group II). Renal deterioration was observed in
      only one case (9%) in Group I (the patient had persistent proteinuria of over 2
      g/day throughout the clinical course and started hemodialysis 12 years after
      delivery), and in 3 cases(11%) in Group II at the end of follow-up. The renal
      survival rate did not significantly differ between the two groups. We concluded
      that delivery does not adversely affect the long-term prognosis of patients with
      LN that is clinically controlled through treatment.

PMID- 11510225
TI  - [Peritoneal sclerosis in children under treatment with peritoneal dialysis].
AB  - Peritoneal dialysis(PD) is an established method of dialysis for children at the
      end stage of renal failure. Among several problems associated with PD, peritoneal
      sclerosis is one of the most serious complications. We examined four children on
      PD who were diagnosed as having peritoneal sclerosis in 1997 and 1998. Three of
      these cases were switched to hemodialysis(HD) and one is now undergoing a switch
      from PD to HD. Although all of the four patients had a history of bacterial
      peritonitis, they had been maintained in a fairly good condition on PD. The mean
      duration of PD was 9 years(4-14 years). All cases were anuric and had been
      maintained on PD without any problems of peritoneal function. From these
      observations, we should consider peritoneal sclerosis even in patients with a
      good clinical condition during the long-term period of PD. We recommend serial
      peritoneal biopsies, at least at the time of peritoneal catheter changes, to
      check for peritoneal sclerosis. The patients who are diagnosed as having
      sclerotic thickening of the peritoneal membrane should be switched from PD to HD
      to prevent the occurrence of life-threatening peritoneal sclerosis.

PMID- 11510226
TI  - [Two cases of exercise-induced acute renal failure with idiopathic renal
      hypouricemia].
AB  - Acute renal failure without oliguria developed in a 25-year-old male and a 19
      year-old male after exercise. Marked hypouricemia became apparent during
      improvement of their renal function. Increased excretion of uric acid into the
      urine, increased fractional excretion of uric acid(clearance ratio of uric acid
      against creatinine), and normal concentration of plasma xanthine and hypoxanthine
      were observed in both cases. Probenecid and pyrazinamide loading test suggesting
      decreased reabsorption of uric acid in the proximal convoluted tubules revealed
      that presecretory reabsorption defect of uric acid resulted in the hypouricemia
      in both cases. These two cases were diagnosed as having idiopathic renal
      hypouricemia.

PMID- 11510227
TI  - [A case of antiphospholipid antibody syndrome with variable renal histological
      change despite of poor changes in urinalysis].
AB  - We experienced a case of lupus nephritis with antiphospholipid antibody syndrome.
      A renal biopsy specimen from this patient showed various renal histological
      changes, but the results of urinalysis were almost normal. The patient was a 56
      year-old woman diagnosed as having systemic lupus erythematosus with
      antiphospholipid antibody syndrome in 1983. In 1998, she had diarrhea and blood
      gas analysis showed metabolic acidosis. Therefore, she was admitted to our
      hospital and underwent renal function examination. The glomerular filtration rate
      was reduced(GFR: 40/ml/min), but urinalysis was almost normal. To examine her
      renal dysfunction, we performed open renal biopsy. Her renal tissues showed
      global glomerular sclerosis, mesangial cell proliferation and infiltration of
      cells in the tubulointerstitial area(WHO II). Furthermore, some arterioles showed
      organized thrombus formation and recanalization due to the antiphospholipid
      antibody syndrome. Renal biopsy of patients with lupus nephritis is useful not
      only for precise diagnosis, but also for the selection of appropriate treatment.

PMID- 11510228
TI  - [Life style and mortality].

PMID- 11510229
TI  - [Language understanding among Nordic physicians. Yes to both the Nordic and the
      international].

PMID- 11510230
TI  - [To practice evidence-based medicine. What does it really say, how do the
      clinicians want the evidence be served and how can the information be refined
      without being out-of-date?].

PMID- 11510231
TI  - [The role of fluorides in the treatment of postmenopausal osteoporosis].

PMID- 11510232
TI  - [Diagnosis of infections. Meningitis].

PMID- 11510233
TI  - [Molecular mechanisms of beta-cell destruction in type 1 diabetes].

PMID- 11510234
TI  - [What do hospital staff's smoking habits mean for knowledge, attitude and
      counseling practice related to smoking?].

PMID- 11510235
TI  - [NSAID--COX-2-inhibitors, where is the difference? Focus on the modes of action].
AB  - Non-steroidal anti-inflammatory drugs (NSAID) induce their action by inhibiting
      prostaglandin synthesis via the cyclooxygenase enzymes (COX). COX has recently
      been shown to have at least two isoforms, termed COX-1 and COX-2. The life
      threatening gastrointestinal side effects of NSAID are caused by their inhibition
      of COX-1, which results in increased gastrointestinal bleeding and decreased
      ability to induce platelet aggregation. Highly specific COX-2 inhibitors are now
      available. These have the same ability to relieve pain, but do not cause
      gastrointestinal bleeding or prolong bleeding time. However, many other side
      effects caused by NSAID are due to COX-2 inhibition and COX-2 inhibitors should
      still be used with caution when patients suffer from lung, heart, or kidney
      diseases.

PMID- 11510236
TI  - [Impact of tobacco, alcohol overconsumption and drug abuse on mortality in
      Denmark. Trends over 25 years, 1973-1997].
AB  - INTRODUCTION: The aim of the study was to estimate the national impact of
      smoking, alcohol, and drugs on mortality. MATERIAL AND METHODS: The analysis was
      based on the cause of death register. Deaths attributable to smoking were
      calculated by an indirect method. Deaths related to alcohol and drugs (illegal
      drugs and prescription drugs) were defined by the underlying and contributory
      causes of death. RESULTS: In the period, 1993-1997, 30% of all deaths in men and
      20% in women were related to tobacco, alcohol, or drugs. The percentages of all
      deaths for tobacco, alcohol, and drugs were respectively 22.8%, 6.3%, and 1.2%
      for men and 16.5%, 2.5%, and 0.7% for women. Every year 12,000 Danes die 11-13
      years prematurely, because of tobacco, more than 2500 die more than 20 years
      prematurely, because of alcohol, and about 600 die almost 30 years prematurely,
      because of drugs. The standardised lifetime risk of death from one of these three
      causes was about 30% for men, highest in the middle five-year period. For women-
      because of substantially increased mortality attributable to smoking--there was a
      large increase from 8% to 20%. In the municipality of Copenhagen, the lifetime
      risk for men was about 50%, for women it increased from 15% in the middle of the
      1970s to more than 30% in the middle of the 1990s. For both men and women,
      mortality in the age group 35-74 declined sharply, when mortality related to the
      three causes was excluded. However, the heavy increase in smoking-related deaths
      in women means that the total mortality over the entire period has been almost
      constant. DISCUSSION: It is a tremendous challenge to change the impact of
      tobacco, alcohol, and drugs on mortality in Denmark.

PMID- 11510237
TI  - [Osteogenesis imperfecta. The effect of intramedullary nails in long tubular
      bones].
AB  - INTRODUCTION: The aim of the study was to describe the clinical, radiological,
      and functional results of intramedullary nailing of deformities in the lower
      extremities of children with osteogenesis imperfecta after the use of multiple
      osteotomies and non-telescoping rods (rush pins). MATERIAL AND METHODS: Eight
      children with osteogenesis imperfecta, who consecutively underwent surgery during
      1991-1994, were entered in the study. RESULTS: Sixteen operations were performed
      on eight children: 12 on the femur and four on the tibia. Like others, we found a
      high complication rate, 50%. Radiological correction of angular deformities was
      good. The functional outcome was satisfactory and the patients were satisfied.
      CONCLUSION: Correction and stabilisation of deformities in the lower extremities
      in children with osteogenesis imperfecta with the use of non-telescoping rods is
      an acceptable method of decreasing fractures and allowing most formerly non
      ambulatory children to walk. Furthermore, the cosmetics were improved.

PMID- 11510238
TI  - [TPO immunostaining of the solitary, cold thyroid nodules].
AB  - INTRODUCTION: The chance of malignancy in scintigraphically cold thyroid nodules
      is 2-24%. Differentiation between malignant and benign cytology is difficult. The
      aim of this study was to evaluate the ability of immunostaining (MoAB47--raised
      against thyroid peroxidase (TPO)) to differentiate between malignant and benign
      cells taken from cold thyroid nodules by fine needle aspiration biopsy (FNAB) in
      order to reduce the number of unnecessary thyroid operations. MATERIALS AND
      METHODS: One hundred and eighty-one patients (150 female) with a
      scintigraphically cold, solitary thyroid nodule were entered between 1993 and
      1996. Fifty-seven were excluded for various reasons. Material removed by FNAB was
      stained with MoAB47 and routine staining. Staining of 80% or more of the cells
      was considered benign, less than 80% was considered malignant. Routine staining
      of operatively removed material was used as the final diagnosis. RESULTS: A
      pattern with negative TPO staining was found in all lesions that were
      subsequently proved to be malignant. In all but one, the lesions subsequently
      diagnosed as being benign stained positive for TPO. The sensitivity and
      specificity were respectively 1.0 and 0.99. CONCLUSION: TPO immunostaining of
      material removed by FNAB is a powerful tool in the differentiation between benign
      and malignant tumours.

PMID- 11510239
TI  - [Endoscopic closure of cranionasal cerebrospinal fluid fistulas with the use of
      neuronavigation--"Computer Aided Surgery"].
AB  - INTRODUCTION: Conventionally, cranionasal cerebrospinal fluid (CSF) fistulas have
      been closed by repair of the dural defect via an open craniotomy. These
      techniques may be cumbersome, not without complications, and far from successful.
      In recent years, endoscopic techniques have been developed in the field of nasal
      surgery and neurosurgery. Furthermore, by means of computer-aided surgery or
      neuronavigation, it is possible to identify the surgical track with a high degree
      of accuracy and, by the same token, identify the defect in the cranium. METHOD:
      By combining the endoscopic technique with computer-aided surgery, we have
      operated on six patients with cranionasal CSF fistulas endonasally. The fistula
      was confirmed before surgery by subaracnoidal injection of fluorescein. RESULTS:
      The surgery was successful and without any complications in all six cases.
      DISCUSSION: The method is recommended as the operation of first choice for
      cranionasal CFS fistulas, as compared to transcranial surgery. It is probably
      more efficient and with fewer complications than conventional surgery. A
      collaboration between neurosurgeons and ENT surgeons, like ours, can be
      recommended.

PMID- 11510240
TI  - [Severe chronic acrylamide intoxication].
AB  - This report of a severe, occupational, long-term acrylamide intoxication with
      permanent peripheral neuropathy, that chemical toxicity is still a hazard at
      Danish workplaces.

PMID- 11510241
TI  - [Posttraumatic hyphema induced by tossed frozen caramel candy].
AB  - The tossing of caramels is a traditional part of the celebrations on the last day
      of school. A case in which a 14-year-old boy suffered a secondary posttraumatic
      hyphaemia induced by a caramel tossed at the patient's left eye is described. The
      condition remitted spontaneously without loss of eyesight.

PMID- 11510242
TI  - [Emergency tracheotomy].

PMID- 11510243
TI  - [Treatment of prolonged critical illness with hypothalamic hormones?].

PMID- 11510244
TI  - [The Roskilde Festival disaster--what about the dialogue between relatives and
      physicians?].

PMID- 11510245
TI  - [End of the Osterberg's chart?].

PMID- 11510246
TI  - [Legionnaires' disease--Turkey].

PMID- 11510247
TI  - [Chronic hepatitis B carriers].

PMID- 11510248
TI  - [Chronic hepatitis B carriers].

PMID- 11510249
TI  - [Honest nutritional counseling concerning vitamin E II].

PMID- 11510250
TI  - [Flexible sigmoidoscopy in Denmark--comments].

PMID- 11510251
TI  - [Why can scabies be of Norwegian origin?].

PMID- 11510252
TI  - Making health care safer: a critical analysis of patient safety practices.
AB  - OBJECTIVES: Patient safety has received increased attention in recent years, but
      mostly with a focus on the epidemiology of errors and adverse events, rather than
      on practices that reduce such events. This project aimed to collect and
      critically review the existing evidence on practices relevant to improving
      patient safety. SEARCH STRATEGY AND SELECTION CRITERIA: Patient safety practices
      were defined as those that reduce the risk of adverse events related to exposure
      to medical care across a range of diagnoses or conditions. Potential patient
      safety practices were identified based on preliminary surveys of the literature
      and expert consultation. This process resulted in the identification of 79
      practices for review. The practices focused primarily on hospitalized patients,
      but some involved nursing home or ambulatory patients. Protocols specified the
      inclusion criteria for studies and the structure for evaluation of the evidence
      regarding each practice. Pertinent studies were identified using various
      bibliographic databases (e.g., MEDLINE, PsycINFO, ABI/INFORM, INSPEC), targeted
      searches of the Internet, and communication with relevant experts. DATA
      COLLECTION AND ANALYSIS: Included literature consisted of controlled
      observational studies, clinical trials and systematic reviews found in the peer
      reviewed medical literature, relevant non-health care literature and "gray
      literature." For most practices, the project team required that the primary
      outcome consist of a clinical endpoint (i.e., some measure of morbidity or
      mortality) or a surrogate outcome with a clear connection to patient morbidity or
      mortality. This criterion was relaxed for some practices drawn from the non
      health care literature. The evidence supporting each practice was summarized
      using a prospectively determined format. The project team then used a predefined
      consensus technique to rank the practices according to the strength of evidence
      presented in practice summaries. A separate ranking was developed for research
      priorities. MAIN RESULTS: Practices with the strongest supporting evidence are
      generally clinical interventions that decrease the risks associated with
      hospitalization, critical care, or surgery. Many patient safety practices drawn
      primarily from nonmedical fields (e.g., use of simulators, bar coding,
      computerized physician order entry, crew resource management) deserve additional
      research to elucidate their value in the health care environment. The following
      11 practices were rated most highly in terms of strength of the evidence
      supporting more widespread implementation. Appropriate use of prophylaxis to
      prevent venous thromboembolism in patients at risk; Use of perioperative beta
      blockers in appropriate patients to prevent perioperative morbidity and
      mortality; Use of maximum sterile barriers while placing central intravenous
      catheters to prevent infections; Appropriate use of antibiotic prophylaxis in
      surgical patients to prevent postoperative infections; Asking that patients
      recall and restate what they have been told during the informed consent process;
      Continuous aspiration of subglottic secretions (CASS) to prevent ventilator
      associated pneumonia; Use of pressure relieving bedding materials to prevent
      pressure ulcers; Use of real-time ultrasound guidance during central line
      insertion to prevent complications; Patient self-management for warfarin
      (Coumadin) to achieve appropriate outpatient anticoagulation and prevent
      complications; Appropriate provision of nutrition, with a particular emphasis on
      early enteral nutrition in critically ill and surgical patients; and Use of
      antibiotic-impregnated central venous catheters to prevent catheter-related
      infections. CONCLUSIONS: An evidence-based approach can help identify practices
      that are likely to improve patient safety. Such practices target a diverse array
      of safety problems. Further research is needed to fill the substantial gaps in
      the evidentiary base, particularly with regard to the generalizability of patient
      safety practices heretofore tested only in limited settings and to promising
      practices drawn from industries outside of health care.

PMID- 11510253
TI  - Lymphocyte subsets in the course of continuous ambulatory peritoneal dialysis.
AB  - The present study evaluated whether estimation of lymphocyte subset counts can be
      more helpful than total lymphocyte count (TLC) in earlier diagnosis of immune and
      nutritional changes in the course of continuous ambulatory peritoneal dialysis
      (CAPD). For the study, 50 CAPD patients were divided into four groups depending
      on dialysis duration. Group I consisted of patients treated for 6-12 months (n =
      15); group II, for 13-24 months (n = 16); group III, for 25-36 months (n = 12);
      and group IV, for more than 36 months (n = 7). Thirteen patients, being 8 +/- 7
      days before CAPD initiation, were included in group 0. Flow cytometry was used
      for estimation of lymphocyte subsets (determination of CD3, CD4, CD8, CD19, and
      CD16 + 56 antigens). Our uremic patients started CAPD therapy with decreased TLC
      and lymphocyte subset (excluding CD16 + 56) counts. After 6-12 months of CAPD
      therapy, a significant increase in TLC, CD4:CD8 ratio, and all examined
      lymphocyte subset counts was observed. In the next years of CAPD therapy, TLC,
      CD3, CD4, CD8, and CD19 cell counts decreased. In patients on CAPD for more than
      36 months, CD3, CD4, CD8, and CD19 cell counts were below the normal range, but
      mean TLC was maintained in the normal range, and CD16 + 56 exceeded the upper
      limit of normal. A significant negative correlation between CD19 cell count and
      dialysis duration was seen (r = -0.298, p = 0.035, n = 50). In conclusion, the
      first months of CAPD therapy see an improvement in immune and nutritional status
      as expressed by an increase in TLC, lymphocyte subset counts, and CD4:CD8 ratio.
      Repeat determinations of CD3, CD4, CD8, and CD19 cell counts indicate that these
      counts decrease earlier than an evaluation of TLC indicates. We recommend
      lymphocyte subset determinations for detection of immune and nutritional
      abnormalities in the course of CAPD treatment. An increase in natural killer
      cells above the normal range may reflect chronic sterile or infectious
      inflammatory response, which deteriorates nutritional status.

PMID- 11510254
TI  - Polyglucose dialysis solution induces changes in blood chemistry.
AB  - In peritoneal dialysis patients, polyglucose dialysis solution (PG-DS) influences
      serum levels of sodium, amylase, and lipase, and of iron parameters. We aimed to
      examine, in the blood or serum of continuous ambulatory peritoneal dialysis
      (CAPD) patients treated with PG-DS, changes in the concentrations of Na+, K+,
      Ca++, total Ca, phosphorus, urea nitrogen, creatinine, uric acid, total protein,
      albumin, and intact parathyroid hormone (iPTH); in lipid profile [total
      cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein
      (LDL) cholesterol, triglycerides, HDL:total cholesterol ratio]; and in acid-base
      status. We started studies in 14 CAPD patients in whom 7.5% PG-DS was applied for
      the overnight 2-L exchange (duration: about 10 hours). Determinations of blood
      chemistry were carried out at 1.6 +/- 0.8 months before the introduction of PG-DS
      (period I, n = 14); after 1.2 +/- 0.6 months (period II, n = 14), 4.4 +/- 0.8
      months (period III, n = 11), and 8.8 +/- 2.4 months (period IV, n = 9) of PG-DS
      administration; and 2.0 +/- 0.6 months after PG-DS discontinuation (period V, n =
      11). The most pronounced (significant) differences in the examined parameters
      were seen between periods I and III or periods I and IV for Na+ (140 +/- 3 mmol/L
      vs 136 +/- 4 mmol/L), K+ (4.2 +/- 0.6 mmol/L vs 4.8 +/- 0.6 mmol/L), total Ca
      (9.4 +/- 1.1 mg/dL vs 10.5 +/- 1.3 mg/dL), urea nitrogen (61.3 +/- 25.9 mg/dL vs
      79.4 +/- 20.9 mg/dL), creatinine (10.7 +/- 2.6 mg/dL vs 12.8 +/- 4.3 mg/dL), uric
      acid (4.8 +/- 2.3 mg/dL vs 7.1 +/- 1.7 mg/dL), and total protein (61.7 +/- 10.8
      g/L vs 70.5 +/- 8.0 g/L). Serum lipid levels were stable during PG-DS
      administration, but they increased after discontinuation of the PG-DS. Other
      studied parameters usually returned to pre-treatment values after PG-DS
      discontinuation. All patients were in good clinical status during the study. The
      changes in blood chemistry did not cause clinical intervention. Our results
      indicate that PG-DS influences blood chemistry. The observed differences need to
      be clinically analyzed.

PMID- 11510255
TI  - Bone mass in chronic renal insufficiency patients treated with continuous
      ambulatory peritoneal dialysis.
AB  - Chronic renal failure (CRF) causes deterioration of the fluid, electrolyte, and
      acid-base balances, azotemia, and impairment of the structure and function of
      many systems. In the skeletal system, CRF changes both the quality and quantity
      of the bone through its multifactorial influence on bone metabolism, leading to
      osteopenia, osteoporosis, and increased risk of fracture. The aim of the present
      study was to work up the quickest and most sensitive schedule for detecting
      osteoporosis in chronic renal insufficiency patients treated with CAPD. Thirty
      seven uremic patients were included in the study. Bone mineral density was
      measured by dual-energy x-ray absorptiometry in lumbar spine, femoral neck,
      forearm (33% distal and ultradistal sites), and total body. Analyzing all five
      sites, we made the assessment that the prevalence of osteoporosis in our group of
      patients reached 48.6%. If only one site was evaluated, the ultradistal part of
      forearm yielded the highest frequency of diagnosis of osteoporosis (37.8%). Next
      came the femoral neck and total body (21.6% each). When the two sites in the
      forearm were taken into account together, the incidence of osteoporosis reached
      40.5%. We conclude that the quickest and most sensitive method of detecting
      osteoporosis in CAPD patients is to measure bone mass in both forearm sites (33%
      distal and ultradistal), then in the femoral neck.

PMID- 11510256
TI  - Role still exists for cycler therapy in anuric patients with a low-transport
      membrane.
AB  - It is generally believed that, to achieve adequacy targets, anuric patients with
      a low-transport membrane should be treated by continuous ambulatory peritoneal
      dialysis (CAPD) or CAPD with a night-exchange device. If adequacy targets are not
      reached, it is suggested that patients should be changed to hemodialysis. We
      would like to show that a role still exists for cycler + therapy (cycler therapy
      with a wet day or with only one manual exchange) in these patients, both for
      obtaining target Kt/V and for lifestyle. Using the PD Adequest computer program
      (Baxter Healthcare Corporation, Deerfield, IL, U.S.A.), we compared a night
      exchange device [3 exchanges during the day and 2 exchanges during the night (3 +
      2)] to various regimes of cycler + therapy. In all cases, the night-exchange
      volume exceeded the day-exchange volume by 500 mL. Using cycler + therapy in
      anuric patients with a low-transport membrane, with 6-7 exchanges over 9 hours,
      Kt/V can be increased by 10%-25%. A role therefore still exists for cycler +
      therapy in anuric patients with a low-transport membrane for lifestyle or to
      achieve a better Kt/V. Unfortunately, we saw no significant improvement in
      creatinine clearance.

PMID- 11510257
TI  - Increased mortality of elderly female peritoneal dialysis patients with diabetes-
      a descriptive analysis.
AB  - Three recent studies using registry data from the United States, in comparing the
      mortality risks between peritoneal dialysis (PD) and hemodialysis (HD), have
      consistently found that elderly diabetic women on PD have a higher mortality risk
      as compared with their counterparts on HD. Though the cause for this observation
      is not clear, the phenomenon may be unique to the United States. Alternatively, a
      selection bias impossible to decipher may be at work in these studies, as none of
      them have data on comorbidity, nutrition, or adequacy of dialysis. Finally, the
      possibility that elderly diabetic women are, for some reason, more vulnerable to
      the ill effects of peritoneal dialysis should be considered. We report here a
      retrospective analysis of 47 diabetic women, above 55 years of age, with end
      stage renal disease, who were started on PD and who later died on dialysis. The
      primary outcome of interest was cause of death. Demographic details about the
      patients, comorbid conditions, dialysis adequacy, and biochemical parameters at
      the start of PD were noted. Death in these patients was attributed mainly to
      vascular causes, and there appeared to be a high prevalence of peripheral
      vascular disease. Infection was the next major cause of death, being the primary
      cause in 14 patients. Of these, only 5 patients had peritonitis. On a Cox
      regression analysis, only patient age and duration of diabetes at onset of
      dialysis were found to be predictive of vascular death. No factor was found to be
      predictive of death from infection. It appears that elderly diabetic women on PD
      die mainly of the long-term complications of diabetes.

PMID- 11510258
TI  - Changing the trend: a prospective study on factors contributing to the growth
      rate of peritoneal dialysis programs.
AB  - Compared with countries worldwide, the United States currently has one of the
      lowest peritoneal dialysis (PD) populations as compared with its hemodialysis
      (HD) population. Approximately 12% of the total dialysis population in the United
      State is on PD. This figure correlates with the take-on rate [percentage of end
      stage renal disease (ESRD) patients enrolling in PD programs] of about 12%-15% in
      the United States. Over a two-year period, we prospectively examined the role
      that developing a comprehensive infrastructure and support system had on
      expanding our PD program. The changes made included these: nephrologists placing
      PD catheters using the laparoscopic method; active identification of, and
      training for, family members and personnel in nursing homes and daycare centers
      to perform PD; improvements in home conditions through support by social workers;
      early ESRD patient education; and provision of in-center intermittent PD (IPD)
      for selected patients. We then compared the results from the two years after
      commencement of the changes against the two years before the changes were made.
      Training of personnel in nursing homes increased enrollment from 3 to 11 patients
      (p = 0.01); training of personnel in daycare centers increased enrollment from 0
      to 5 patients (p = 0.05); training family members and providing family support
      increased enrollment from 4 to 15 patients (p = 0.03); early patient and family
      education increased enrollment from 4 to 24 patients (p = 0.008); improving home
      conditions increased enrollment from 1 to 14 patients (p = 0.01); and providing
      an IPD program for selected patients added 6 patients (p = 0.05). Introducing a
      program for nephrologists to place PD catheters by the laparoscopic technique
      decreased catheter mechanical failure (and subsequent transfer to HD), from 22 to
      3 patients (p = 0.005). Our PD take-on rate (percentage of ESRD patients choosing
      PD modality) increased from 19% to 76% (p = 0.002). The total number of patients
      in the PD program over the two years after initiation of the changes increased
      from 33 to 93 (p = 0.01), while the number of HD patients decreased from 168 to
      142 (p = 0.05). Developing a comprehensive infrastructure and support system for
      PD programs permits enrollment of patients who otherwise would have been excluded
      as PD candidates and eliminates loss of PD patients to HD. Implementation of such
      programs can contribute considerably to enhancing the PD population growth rate.

PMID- 11510259
TI  - Relationship between intraperitoneal bleeding, adhesions, and peritoneal dialysis
      catheter failure: a method of prevention.
AB  - Intraperitoneal (i.p.) bleeding causes intense inflammatory reactions and
      extensive adhesions. The relationship between i.p. bleeding and adhesions is well
      documented in both animal and human studies. Over an 8-year period, we performed
      362 permanent peritoneal dialysis (PD) catheter placements in 317 patients, using
      the laparoscopic technique. In the first 203 procedures (group I), we observed
      intra-operative bleeding in 12 patients (intra-operative i.p. bleeding seen
      laparoscopically, and significant blood-tinged dialysate irrigation). Patients
      were left dry for 3-5 days before dialysate instillation during the break-in
      period. During the break-in period, 7 of the 12 patients (58%) developed primary
      catheter failure requiring catheter removal (p = 0.03). All 7 patients underwent
      repeat laparoscopy for placement of a new catheter. In all 7 patients,
      laparoscopy showed significant adhesions. In the subsequent 159 procedures (group
      II), we observed intra-operative bleeding in 10 patients. We irrigated the
      peritoneal cavity repeatedly, until clear dialysate was obtained, then instilled
      500-1000 mL 1.5% Dianeal solution (Baxter Healthcare Corporation, Deerfield, IL,
      U.S.A.) and capped the catheter. These patients were then placed on low-volume
      continuous cycling peritoneal dialysis [(CCPD) 700-1200 mL, based on the
      patient's size, every 2 hours, until the effluent became clear]. Following this,
      patients underwent daily irrigation and PD fluid cell count, and were left with
      700-1200 mL dialysate to dwell. The process was continued until PD fluid drainage
      showed no red blood cells or until the patient was started on routine peritoneal
      dialysis. None of these patients were drained dry. Compared with group I, no
      patient among the 10 in group II developed catheter failure (p = 0.001), and mean
      catheter survival was 31 +/- 7 months. Of the 10 patients, 2 developed exist-site
      leaks, both after clearance of red blood cells from the drained dialysate. None
      developed peritonitis. We conclude that intra-operative i.p. bleeding associated
      with significant blood-tinged dialysate irrigation may lead to local adhesions if
      the peritoneum is drained dry. The result may be loss of the PD catheter in about
      60% of cases. Continuous irrigation, combined with a moderate amount of Dianeal
      solution left to dwell, or early initiation of low-volume PD, or both, prevents
      this complication.

PMID- 11510260
TI  - Diabetic patients on peritoneal dialysis need less erythropoietin to maintain
      adequate hemoglobin.
AB  - Peritoneal dialysis (PD) patients have been shown to require less erythropoietin
      as compared with hemodialysis (HD) patients to maintain similar hemoglobin
      values. In our unit, we observed that diabetic PD patients required less
      erythropoietin treatment than did other PD patients. We therefore compared the
      amount of erythropoietin needed in diabetic and non diabetic patients on PD to
      maintain a similar hemoglobin value. All polycystic patients were excluded from
      the study because they rarely require erythropoietin. We also excluded patients
      with bone marrow disease, active gastrointestinal bleeding, or patients very
      resistant (requiring more than 25,000 U per week) to Eprex (recombinant human
      erythropoietin: Janssen-Cilag, North York, Ontario, Canada). Patients not
      requiring Eprex were also excluded from the study. We calculated the weekly
      erythropoietin dose in the two groups. We also compared hemoglobin level, iron
      transferrin saturation, vitamin?12 level, and serum folate. Diabetic patients
      required a lower weekly erythropoietin dose. Diabetic PD patients in our unti
      receive an average 4497 U per week compared with 7593 U per week for non diabetic
      PD patients. The difference (approximately 3000 U per week) is statistically
      significant.

PMID- 11510261
TI  - Incisional hernia after corrective omentectomy for peritoneal dialysis catheter
      malposition.
AB  - Laparotomic correction with or without omentectomy is occasionally required for
      malposition of a peritoneal dialysis (PD) catheter. We reviewed the incidence of
      incisional hernia following laparotomic PD catheter correction with or with
      omentectomy. From January 1996 to December 1998, PD catheters were implanted by
      non open-dissection technique using a trocar in 148 patients. Laparotomy for PD
      catheter malposition was required in 20 of the 148 patients. Omentectomy was
      performed simultaneously in 11 patients. After laparotomy, the wound was closed
      with interrupted or continuous layered polyglycolidelactide polymer sutures.
      Dialysis was resumed after the third or fourth day. Incisional hernia developed
      in 30% (6/20) of all patients undergoing laparotomy, but in none of the patients
      not undergoing laparotomy. The incidence increased when omentectomy was performed
      [5/11 (45.5%) vs 1/9 (11.1%)]. Multiparity, female sex, and laparotomy at a later
      time also predisposed to development of incisional hernia. Among the patients
      with incisional hernia, 2 patients showed multiple recurrences and 1 patient
      showed later leakage; PD catheters were lost in these patients. Another 3
      patients continued continuous ambulatory peritoneal dialysis (CAPD) without a
      recurrence. The results suggest that incisional hernia is prevalent following
      laparotomic PD catheter correction, especially when omentectomy is performed
      simultaneously. Situations that seem to increase the risk of incisional hernia-
      inevitably encountered during corrective laparotomic omentectomy--are discussed.
      An evaluation is necessary concerning whether omentectomy acts as an independent
      risk factor for incisional hernia, and whether incisional hernia occurs more
      frequently when omentectomy is performed after a period on CAPD as compared with
      when it is performed at the time of PD catheter implantation. Laparotomic
      omentectomy should be performed as a last resort for the correction of PD
      catheter malposition.

PMID- 11510262
TI  - Alpha replacement method for displaced peritoneal catheter: a simple and
      effective maneuver.
AB  - Displacement of the peritoneal catheter tip is one of the most frequent causes of
      catheter malfunction. As a consequence, appropriate peritoneal effluent drainage
      is impossible. Alternatives to catheter exchange or invasive abdominal
      intervention did not appear until the alpha maneuver was described by Yoshihara
      et al. We review our experience with this maneuver over the last 7 years. We used
      the alpha maneuver in 24 peritoneal dialysis (PD) patients (13 men and 11 women)
      with a mean age of 52 +/- 16 years. Some patients required several repeat
      procedures (total procedures: 32). The mean time between placement of the
      catheter and performance of the alpha maneuver was 6.5 +/- 7.9 months. In all
      patients, the technique was indicated for problems with peritoneal effluent
      drainage, after verification of catheter tip displacement by radiologic
      examination. In 6 patients, the initial maneuver was unsuccessful and had to be
      repeated. The first maneuver was effective in 11 of 24 cases (46%) and
      unsuccessful in the other 13 (54%). No differences in sex, renal disease, or age
      were seen between the two groups. The mean time between catheter placement and
      tip displacement detection was significantly lower in the cases of ineffective
      maneuver (2.7 +/- 4.3 months) than in those that met with success (10.8 +/- 9
      months). In other words, 84% of unsuccessful maneuvers were performed in the
      first 3 months of catheter life. Of the 11 patients successfully treated, 6
      continued on PD for 14.7 +/- 6.3 months. Two other patients were transplanted
      with normal-functioning catheters, and two more left PD (after 10 and 17 months)
      for reasons unrelated to the catheter. One patient required a catheter change
      owing to breakdown in the Silastic after disruption by the metallic guide, which
      perforated the catheter wall. The 13 ineffective maneuvers involved 7 omentum
      entrapments, 1 procedure that was repeated effectively 15 days later, and 5
      definite failures requiring catheter change. The failure rate may therefore be
      considered to be 20.8%, taking into consideration that omentum entrapment should
      not be an indication for the procedure. We conclude that the alpha maneuver for a
      displaced peritoneal catheter is a simple and effective procedure that can be
      applied at the patient's bedside. In consequence, it should be the technique of
      first choice in these situations. Only when the alpha maneuver fails should
      invasive methods, including catheter change, be considered.

PMID- 11510263
TI  - Cardiovascular comorbidity and mortality in patients starting peritoneal
      dialysis: an American midwestern center experience.
AB  - End-stage renal disease (ESRD) patients frequently have multiple comorbidities,
      and cardiovascular disease remains the leading cause of death in these patients.
      The objectives of the present study were (1) to characterize the number and
      severity of cardiovascular comorbidities at the start of peritoneal dialysis
      (PD), and (2) to determine the impact of these comorbidities on mortality. We
      retrospectively studied all ESRD patients starting peritoneal dialysis at our
      center between 1990 and 1999. The baseline cardiovascular comorbid factors were
      categorized as ischemic heart disease, congestive heart failure, arrhythmia,
      peripheral vascular disease, and cerebrovascular disease. The severity of each
      factor was scored from 0 to 3. The number of comorbidities and the total
      cardiovascular comorbidity severity scores were determined for each patient.
      Cardiovascular deaths included those attributed to sudden death, cardiac disease,
      cerebrovascular disease, and complications of peripheral vascular disease. Of the
      191 patients, 105 were men, and 105 (55%) had diabetes mellitus. The mean age was
      60.8 +/- 13.3 years and the mean time on PD was 18.8 +/- 16.3 months. As the
      number of cardiovascular comorbidities increased, the proportion of patients who
      died of cardiovascular causes increased eighteen-fold. At each level of
      cardiovascular comorbidity, diabetic patients starting dialysis were younger, and
      their survival time was shorter as compared with non diabetic patients. Baseline
      comorbidity determination is important, as comorbidities are prognostic
      harbingers of eventual complications.

PMID- 11510264
TI  - Outcome of percutaneous endoscopic gastrostomy feeding in patients on peritoneal
      dialysis.
AB  - Protein malnutrition is now well established as an important contributory factor
      to the high mortality in peritoneal dialysis (PD) patients. Low dietary protein
      calorie intake is one of the factors leading to protein malnutrition. If PD
      patients develop difficulty eating, percutaneous endoscopic gastrostomy (PEG)
      feeding may prove beneficial in providing adequate nutrition. Studies on the
      effectiveness of PEG feeding in PD patients are limited to pediatric patients.
      The objective of the present study was to assess the outcome of PEG feeding in
      adult patients with end-stage renal disease (ESRD) on PD. We retrospectively
      reviewed charts from May 1992 to February 2000 of 10 consecutive patients in our
      center who had had feeding tubes inserted. The patients' ages ranged from 37 to
      81 years, with mean age of 65. Of the 10 patients, 7 were male, 5 were diabetic,
      and 1 was infected with the human immunodeficiency virus. Two patients had
      cerebrovascular accident (CVA) with dysphagia, 3 had multi-infarct dementia, 2
      had anoxic encephalopathy, 2 had dementia, and 1 had calciphylaxis with anorexia.
      Of the 10 patients, 9 failed to eat because of neurologic disorders. Two patients
      who had functioning PEG feedings before starting PD had no complications. Only 2
      of 8 patients already on PD continued with long-term PD after a PEG was inserted.
      Both patients whose PD was not interrupted at the time of PEG placement
      immediately developed peritonitis. Of the 6 patients who were maintained on
      hemodialysis (HD), 2 developed peritonitis within one week of starting PEG
      feedings. The other 4 had no complications from PEG feedings while being
      maintained on HD, but 1 developed peritonitis when PD was resumed. Of the 5
      patients who developed peritonitis, 3 experienced fungal peritonitis. In PD
      patients, PEG feeding is associated with frequent complications. However, PEG
      placement prior to PD initiation appears to be safe. Maintaining patients on HD
      for at least 6 weeks appears to decrease the incidence of peritonitis, but does
      not eliminate it. Use of anti-fungal prophylaxis and maintenance of the patient
      on HD for longer than 6 weeks may produce better results.

PMID- 11510265
TI  - Heme oxygenase-1 regulates vascular tone of the peritoneum undergoing peritoneal
      dialysis.
AB  - The present study investigated the role of heme oxygenase-1 (HO-1) in regulating
      the vascular tone of the peritoneum undergoing peritoneal dialysis. First, we
      used reverse-transcriptase polymerase chain reaction (RT-PCR) to measure changes
      in the expression of HO-1 mRNA in the peritoneum of dehydrated Wistar Kyoto (WKY)
      rats. Second, we used a charge-coupled-device (CCD) camera to measure changes in
      the diameter and blood flow in the small artery of the peritoneum after
      intravenous administration of saline, hemin (4-12 mumol/kg), and tin
      protoporphyrin (4-12 mumol/kg) in dehydrated WKY rats. In non dehydrated rats
      (control), no expression of HO-1 mRNA in the peritoneum was seen. In dehydrated
      and 10% glucose-treated dehydrated rats, HO-1 expression was significantly
      enhanced as compared with the control rats. Intravenous administration of saline
      induced no significant changes in the diameter of the small artery in dehydrated
      WKY rats. Intravenous administration of hemin induced a significant increase in
      the diameter of the small artery in dehydrated WKY rats. Intravenous
      administration of tin-protoporphyrin induced a significant reduction in the
      diameter of the small artery in dehydrated WKY rats. Our results suggest that 10%
      glucose injection into the peritoneal cavity induces overexpression of HO-1 in
      the peritoneum of dehydrated rats. In addition, HO-1 regulates peritoneal
      function by the regulation of vascular tone in the peritoneum.

PMID- 11510266
TI  - Inflammation, peritoneal transport, and response to erythropoietin in peritoneal
      dialysis patients.
AB  - The aim of the present study was to examine the association between 4-hour
      dialysate-to-plasma ratio of creatinine (D/PCr), erythropoietin (EPO)
      responsiveness [EPO (U/week)/hemoglobin (g/L)], and C-reactive protein (CRP).
      Subjects were 54 prevalent peritoneal dialysis (PD) patients [mean age: 58 years;
      30 women, 24 men; 28 with diabetes; 15 on continuous ambulatory peritoneal
      dialysis (CAPD); 39 on continuous cycling peritoneal dialysis (CCPD); mean Kt/V:
      2.44]. In 17 patients, CRP was elevated (> 15 mg/L), and in 39 patients, 4-hour
      D/PCr was high or high-average (> or = 0.65). Mean hemoglobin (Hb) was 115.5 +/-
      12.9 g/L; median EPO dose was 2800 U/week, and median EPO/Hb was 24.5. A
      nonsignificant negative correlation was noted between CRP and hemoglobin (r = 
      0.25, p = 0.07), but no correlations were seen between CRP and 4-hour D/PCr, or
      hemoglobin and 4-hour D/PCr. No correlation was seen between EPO/Hb and 4-hour
      D/PCr or CRP. Multiple linear regression (stepwise, alpha = 0.05) was performed
      with outcome hemoglobin and independent variables EPO [U/week (forced in)],
      percent transferrin saturation [TSAT (forced in)], age, sex, diabetes mellitus,
      serum albumin, CRP, time on PD, 4-hour D/PCr, normalized protein catabolic rate
      (nPCR), ferritin, intact parathyroid hormone (iPTH), aluminum, and angiotensin
      converting enzyme inhibitor (ACEI) use. Serum albumin (1.27, p < 0.01) and
      diabetes mellitus (-6.69, p = 0.04) were the only significant predictors of
      hemoglobin. With serum albumin removed from the model, age (but not CRP) became
      significant. These results do not support an association between peritoneal
      transport and EPO responsiveness, mediated by inflammation. The association
      between serum albumin and hemoglobin appears to be confounded by age more than by
      inflammation.

PMID- 11510267
TI  - Is interleukin-6 concentration in the dialysate of continuous ambulatory
      peritoneal dialysis patients a prognostic parameter in peritonitis?
AB  - In continuous ambulatory peritoneal dialysis (CAPD) patients, peritonitis is a
      dangerous complication. Chemical examinations in the dialysate can be
      successfully used to assess permeability disturbances, hemostatic balance, and
      (for early detection and follow-up) cellular inflammatory reaction. In 7 CAPD
      patients (age: 50 +/- 15 years; dialysis duration: 40 +/- 24 months) with
      peritonitis episodes, and in 17 age-matched CAPD patients (age: 50 +/- 13 years;
      dialysis duration: 29 +/- 18 months) without peritonitis, we examined daily
      dialysate cell count (CC) and concentrations of albumin (ALB), immunoglobulin G
      (IgG), thrombin-antithrombin III complex (TAT), D-dimer (DD), and interleukin-6
      (IL-6) after the long dwell (8-10 hours) over an interval of at least 14 days. In
      CAPD patients with peritonitis episodes, all parameters (CC, ALB, IgG, TAT, DD,
      IL-6) were significantly increased in the first days [IL-6 mean: 25,190 pg/mL
      (range: 2560-52,708 pg/mL) vs 66 pg/mL (range: 21-163 pg/mL)]; then, up to day 14
      after successful therapy with antibiotics, the levels showed no differences as
      compared with CAPD patients without peritonitis. In the case of relapse of
      peritonitis (4 cases), concentration of IL-6 rose again on day 14, 1 day earlier
      than did the other parameters. Determination of IL-6 in the dialysate is a
      reliable prognostic parameter for the course of peritonitis (start, end, relapse)
      in CAPD patients.

PMID- 11510268
TI  - Method for studying development of colonization and infection of dialysis
      catheters.
AB  - Microbial colonization and infection of dialysis catheters is the major cause of
      catheter failure. The present study aimed to develop a method to permit the study
      of microbial biofilm formation and antibiotic prophylaxis and therapy. Standard
      silicon rubber and silver-impregnated catheters were sectioned into 1 mm slices
      and placed into 1-cm x 2-cm culture slide chambers. Fresh clinical isolates were
      obtained from infected patients and suspended in concentrations of 10(3), 10(6),
      and 10(9) colony forming units (CFU) per milliliter in a variety of liquid
      suspending culture media, which included serum protein constituents. Antibiotics
      could be added to the suspending fluid to determine prophylactic activity, or at
      any time thereafter to determine therapeutic activity. The catheter sections were
      incubated with the microbial challenge for 6 hours, 12 hours, 24 hours, and 48
      hours and then washed in flowing distilled water to remove unattached biofilm.
      They were then stained with acridine orange, which fluoresces microbial DNA, and
      were examined by confocal scanning laser microscopy. Biofilm formation,
      representing colonization and infection, were quantified by comparing the
      fluorescent pixel analysis of the uninoculated control with the challenged
      catheter. The method was reproducible and permitted quantitative analysis.
      Standard silicon rubber catheters demonstrated greater biofilm formation than
      silver-impregnated catheters. The method examines the factors involved in
      microbial colonization and infection, and in antibiotic prophylaxis and therapy.

PMID- 11510269
TI  - Treatment of mycobacterial exit-site infections in patients on continuous
      ambulatory peritoneal dialysis.
AB  - Exit-site infections (ESIs) are frequently due to gram-positive organisms and
      occasionally to gram-negative organisms. Initial empiric antibiotic therapy is
      therefore directed against these organisms until culture reports are available.
      Two cases of ESI associated with Mycobacterium are here reported. The first
      patient, a 63-year-old man with type 2 diabetes, recently treated for
      Staphylococcus epidermidis peritonitis, presented with acute purulent drainage at
      the catheter exit site, accompanied by pain and erythema. No tunnel abscess was
      identified by ultrasound. Empiric antibiotic therapy was initiated with ofloxacin
      and vancomycin. A rapid-growing acid-fast bacillus (AFB) noted four days after
      culture was eventually identified as Mycobacterium fortuitum. Ofloxacin was
      continued, vancomycin was discontinued, and clarithromycin was added. The ESI
      initially showed improvement; therapy was therefore continued for several months.
      However, cultures remained positive for M. fortuitum, and the catheter was
      removed 5 months after therapy was initiated. The second patient, a 28-year-old
      woman, presented with severe pain and tenderness at the exit site without
      erythema or drainage. Empiric therapy with cefazolin, gentamicin, and cephalexin
      was initiated. Gram-positive cocci and an AFB were identified from the exit-site
      culture, and antibiotics were initially changed to clarithromycin,
      trimethoprim/sulfamethoxazole, and ofloxacin. The organisms were subsequently
      identified as M. chelonae-M. abscessus complex and coagulase-negative
      Staphylococcus. The patient continued to improve after 3 weeks of antibiotic
      therapy. However, despite the initial improvement in the ESI, the M. chelonae-M.
      abscessus complex continued to grow, and amikacin was added intravenously.
      Despite continued treatment, the ESI did not resolve, and the catheter was
      removed after 4 months of therapy. Despite unusual exist-site infections with
      rapidly growing AFBs, both patients continued continuous ambulatory peritoneal
      dialysis (CAPD) while undergoing treatment for ESI. Catheters were left intact,
      as improvement was initially seen with no evidence of tunnel infection or
      peritonitis. Rapid-growing AFB should be considered another possible causative
      agent for ESI. Two cases of atypical mycobacterial exit-site infection are
      presented to illustrate the difficulties in managing this complication of
      peritoneal dialysis. Ofloxacin--or other quinolones--may provide a better
      spectrum of coverage when choosing empiric therapy in patients presenting with
      ESI.

PMID- 11510270
TI  - Non Candida albicans fungal peritonitis in continuous ambulatory peritoneal
      dialysis patients.
AB  - We report four episodes of non Candida albicans peritonitis (NCAP) in 3 patients
      on continuous ambulatory peritoneal dialysis (CAPD). Risk factors for NCAP
      included diabetes mellitus and prior antibiotic use in half of the cases. The
      antibiotic treatment was prescribed for exit-site infection (ESI) or peritonitis
      in the patient. Treatment for NCAP included antifungal therapy with oral
      fluconazole or intravenous amphotericin B. The NCAP resulted in catheter loss in
      100% of the patients over time. Initial catheter salvage in one patient was
      followed 6 months later by catheter loss following treatment of a bacterial
      peritonitis that was complicated by the development of Candida (Torulopsis)
      glabrata peritonitis unresponsive to treatment with intravenous amphotericin B.
      Although the literature suggests that Candida peritonitis responds to oral
      fluconazole with and without catheter removal, this series suggests that the
      treatment of NCAP includes removal of the peritoneal dialysis catheter with
      appropriate antifungal agents.

PMID- 11510271
TI  - The case for oral treatment of peritonitis in continuous ambulatory peritoneal
      dialysis.
AB  - Among several regimes used in the oral treatment of continuous ambulatory
      peritoneal dialysis (CAPD)--related peritonitis, ciprofloxacin and ofloxacin
      showed the higher treatment efficacy, with an overall cure rate of 80% over a
      treatment duration of 10-16 days. The antimicrobial activity of these agents
      against gram-positive episodes was equal to or even higher than that against
      other peritonitis episodes, and the effectiveness of oral ciprofloxacin can be
      further increased either by an additional intraperitoneal dose for the first 1-5
      days, or by a simultaneous intraperitoneal dose of vancomycin in the first 24
      hours. Clinical resistance to the new quinolones has been uncommon. The possibly
      increasing resistance to ciprofloxacin is a consequence of suboptimal dosing,
      with the resulting low local concentrations of the antibiotic. Oral treatment
      with quinolones provides a good therapeutic alternative to more widely used
      antibiotics for initial treatment of peritonitis episodes. However, more
      extensive data from comparative randomized studies with agents administered
      orally and intraperitoneally would be able to clearly elucidate the overall
      safety and success of oral treatment of PD-related peritonitis with quinolones or
      any new agent.

PMID- 11510272
TI  - Sclerosing encapsulating peritonitis: a case series from a single U.K. center
      during a 10-year period.
AB  - Sclerosing encapsulating peritonitis (SEP) is a serious complication of
      peritoneal dialysis (PD). Previous reports place the prevalence of SEP at 0.54%
      7.3%. We estimated the prevalence of SEP in our unit to be 1.4% over the period
      1989-1999. We here present the 6 identified cases. All of the patients presented
      with small-bowel obstruction; hemorrhagic ascites was identified in 3 cases. All
      6 patients experienced ultrafiltration inadequacy, and 5 were treated with
      glucose polymer (icodextrin; duration of treatment: 1 month-2.5 years).
      Peritoneal dialysis was stopped at the time of diagnosis in 2 cases. In the other
      4 cases, PD had been withdrawn some time prior to the SEP being diagnosed (2
      weeks-5 years). Five of the patients have died; the 6th currently uses
      hemodialysis.

PMID- 11510273
TI  - The long-term effects of single peritonitis episodes on peritoneal equilibration
      test results in continuous ambulatory peritoneal dialysis patients.
AB  - The present study evaluates the long-term effects of single peritonitis episodes
      on peritoneal equilibration test (PET) results in continuous ambulatory
      peritoneal dialysis (CAPD) patients. Twenty-five patients (10 men, 15 women) with
      a mean age of 37.4 +/- 18.7 years were enrolled in this study because all had
      uneventful peritoneal dialysis periods for more than one year after a first
      peritonitis episode. Data from a total of 69 PETs were available [25 from before
      the first peritonitis episode (initial PET), 23 within 1 year after the episode
      (1-year PET), and 21 within 1-2 years after the episode (2-year PET)]. The
      changes in the PET results were evaluated using the dialysate-to-plasma ratio of
      creatinine (D/PCr) and the dialysate-to-instilled glucose ratio (D4/D0) after a 4
      hour dwell. The mean values of D/PCr and D4/D0 showed no statistically
      significant changes between the initial PETs, 1-year PETs, and 2-year PETs.
      However, analysis of the results for patients with culture-positive peritonitis
      (n = 17) revealed significant changes in the mean values of D/PCr and D4/D0
      between the initial PET and the 2-year PET (0.63 +/- 0.06 vs 0.70 +/- 0.09, p =
      0.01; and 0.41 +/- 0.05 vs 0.37 +/- 0.06, p = 0.04, respectively). The long-term
      effect of a definite bacterial peritonitis episode seems to be an increase in
      small-molecule transport. In patients with culture-negative peritonitis, the
      episode had less impact on peritoneal transport.

PMID- 11510274
TI  - Effect of prednisolone on increased expression of laminin by human peritoneal
      mesothelial cells cultured with high glucose.
AB  - This study aimed to clarify the role of laminin (a component of the extracellular
      matrix) in the mechanism of peritoneal fibrosis in continuous ambulatory
      peritoneal dialysis (CAPD) patients, and the effect of prednisolone on such
      fibrosis. We used semiquantitative reverse-transcriptase polymerase chain
      reaction (RT-PCR) and ELISA to study laminin mRNA expression and laminin protein
      production by human peritoneal mesothelial cells (HPMCs) cultured under various
      conditions. After 6 hours, medium 199 with a high glucose content (4.0%)
      increased laminin mRNA expression by 1.38-fold relative to control medium (0.1%
      glucose). Prednisolone (1 mumol/L) suppressed this increase by 92.9%. The laminin
      protein level in culture supernatant was increased 1.83-fold after incubation for
      24 hours in high-glucose medium. Prednisolone (1 mumol/L) suppressed this
      increase by 58.3%. The effects of prednisolone were prevented by a glucocorticoid
      receptor antagonist (RU486) at 100 mumol/L. We conclude that culture of HPMCs in
      high-glucose medium increases laminin mRNA and protein expression, while
      prednisolone suppresses these changes via the glucocorticoid receptor, suggesting
      that prednisolone may prevent peritoneal fibrosis in CAPD patients.

PMID- 11510275
TI  - Renin-angiotensin system plays an important role in the regulation of water
      transport in the peritoneum.
AB  - The present study was carried out to investigate changes in the expression of
      aquaporins (AQPs) in the peritoneum. The effects of the renin-angiotensin system
      on the expression of AQPs with and without angiotensin converting enzyme
      inhibitor (ACEI) or angiotensin II type 1a receptor blocker (ARB) were then
      examined. We divided 20 male Wistar Kyoto (WKY) rats into four groups, dialyzed
      with these solutions: saline; 10% glucose (TZ); 10% glucose plus benazepril
      (ACEI: 4 mg/kg daily); and 10% glucose plus valsartan (ARB: 10 mg/kg daily). The
      ACEI and ARB were administered into the peritoneum for 7 days. Expression of AQP
      1-AQP-4 mRNA was studied by semiquantitative reverse-transcription polymerase
      chain reaction (RT-PCR). Ultrafiltration volume (UFV) and peritoneal function
      were measured by peritoneal equilibration test (PET). In the TZ group, expression
      of AQP-1 and AQP-4 was enhanced in parallel with an increment in UFV. Expression
      of AQP-1 and AQP-4 was also observed in the mesothelium by immunofluorescence
      microscopy. On the other hand, in ACEI- and ARB-treated rats, expression of AQP-1
      and AQP-4 was significantly suppressed, accompanied by loss of UFV. Our results
      suggest that the renin-angiotensin system plays an important role in the
      regulation of water transport in the peritoneum. Administration of ACEI or ARB in
      patients undergoing continuous ambulatory peritoneal dialysis should be carried
      out with caution.

PMID- 11510276
TI  - Treatment options for encapsulating peritoneal sclerosis based on progressive
      stage.
AB  - Sclerosing encapsulating peritonitis (SEP) is recognized as a serious
      complication of peritoneal dialysis. However, recovery is possible if an
      appropriate diagnosis and treatment are made. The term SEP is used most often,
      but is inaccurate, particularly the reference to peritonitis. A more accurate
      description would be "encapsulating peritoneal sclerosis" (EPS). From the
      therapeutic perspective, the diagnosis should be established before EPS develops.
      Early diagnosis is important. Furthermore, it is also important to determine the
      therapeutic tactics for EPS according to the disease stage. Most cases of EPS
      develop with manifestations of fever, increased levels of C-reactive protein
      (CRP), and slight ileus symptoms, accompanied by increased ascites ("inflammatory
      stage"). Following precise identification of the inflammatory stage, steroid
      administration should be initiated immediately with the onset of EPS.
      Methylprednisolone pulse therapy is recommended during the early stage. If the
      EPS is not relieved, or if it recurs within 1 month, the steroid dose should be
      decreased and the patient should be managed by total parenteral nutrition (TPN)
      ("encapsulating stage"). If ileus symptoms remain despite the absence of
      inflammatory findings and decreased ascites, laparotomy and enterolysis should be
      considered within 6 months ("ileus stage"). However, it is important that the
      enterolysis be performed without damaging the capsule-covered intestine. To date,
      we have successfully treated EPS in 18 of 19 patients using these options. In 3
      patients, EPS was relieved by steroid administration. In 15 patients, EPS was
      relieved by total intestinal enterolysis. Enterolysis patients had satisfactory
      operative outcomes and eventually returned to their previous social activities.
      One patient experienced perforation of the small intestine and pan-peritonitis,
      and died of sepsis. In summary, EPS is not an incurable disease. It can be
      completely overcome by active diagnosis and treatment.

PMID- 11510277
TI  - The outcome of peritonitis in patients on automated peritoneal dialysis.
AB  - We reviewed all peritonitis over the last decade to compare patient outcomes on
      automated peritoneal dialysis (APD) and continuous ambulatory peritoneal dialysis
      (CAPD). There were 327 episodes of peritonitis in 198 patients during this
      period. The rates were 0.57 per patient-year and 0.55 per patient-year on APD and
      CAPD respectively. For 52% of the episodes, the patients were admitted and
      managed with a mixture of CAPD and APD, so that no further analysis of outcomes
      was performed. For 48% (158) of the episodes, the patients were treated as
      outpatients and remained on their existing modality: 49 on APD and 100 on CAPD (9
      catheter-related peritonitis excluded). In the APD group, 5 catheters were
      eventually removed for recurrent or refractory peritonitis. One other patient
      died in conjunction with peritonitis. Therefore, the adverse outcome was 12% on
      APD (6/49 episodes). In the CAPD group, 5 catheters were removed for refractory
      or relapsing peritonitis (including 1 for peritonitis with a leak). One other
      patient with fungal peritonitis died. Therefore, the adverse outcome on CAPD was
      6% (6/100 episodes), which is not statistically different from the 12% on APD (p
      = 0.21). In summary, the incidence of peritonitis was similar on APD and CAPD,
      with one half the patients in each group requiring admission. In peritonitis
      treated on an outpatient basis, failure was twice as high with continuation of
      APD as compared with continuation of CAPD, but the difference was nonsignificant.
      Further studies on managing peritonitis in patients on APD are needed.

PMID- 11510278
TI  - Predictors of serum albumin level in patients receiving continuous ambulatory
      peritoneal dialysis.
AB  - Hypoalbuminemia is the strongest predictor of death in patients with renal
      failure. We planned to investigate the factors influencing serum albumin levels
      in continuous ambulatory peritoneal dialysis (CAPD) patients. We prospectively
      followed 100 CAPD patients for 18.6 +/- 12.8 months. The parameters searched for
      a correlation with serum albumin levels were: peritoneal transport kinetics;
      presence of nephrotic syndrome; biochemical parameters; anthropometric
      measurements; and subjective global assessment (SGA). Older patients (age > or =
      60 years), patients with diabetes mellitus or amyloidosis, high and high-average
      transporters, and those with nephrotic syndrome had significantly lower albumin
      levels throughout the follow-up. In addition, significantly lower albumin levels
      were found in patients who were in the SGA "malnourished" categories and those
      who had iPTH levels < or = 65 pg/mL. Albumin level was negatively correlated with
      age, C-reactive protein (CRP), and fibrinogen level; it was positively correlated
      with total cholesterol, intact parathyroid hormone (iPTH) level, and triceps skin
      fold thickness. By regression analysis, age [risk ratio (RR): 0.2437], presence
      of diabetes mellitus (RR: 0.1421) and high or high-average transport status (RR:
      0.1156) were independent predictors of hypoalbuminemia (< or = 3.5 g/dL). In
      conclusion, development of hypoalbuminemia is multifactorial in CAPD patients.
      Older age, cause of renal failure, transport status, chronic inflammation,
      presence of nephrotic syndrome, and nutrition status are important determinants
      of hypoalbuminemia.

PMID- 11510279
TI  - Oral intake and serum levels of ascorbic acid in continuous ambulatory peritoneal
      dialysis patients.
AB  - Oral intake of ascorbic acid is essential for optimum health in human beings.
      Continuous ambulatory peritoneal dialysis (CAPD) patients have an increased need
      for ascorbic acid, because of increased loss through dialysate, reduced intake
      owing to nausea and loss of appetite, and increased oxidative stress. However,
      optimum intake is still controversial. We studied 50 clinically stable patients
      to determine the relationship between oral ascorbic acid intake and serum
      ascorbic acid (SAA) level. Total oral intake ranged from 28 mg daily to 412 mg
      daily. Only one patient had an oral intake of ascorbic acid below 60 mg per day.
      The SAA levels ranged from 1 mg/L to 36.17 mg/L. Although a strong correlation
      existed between intake and SAA (p < 0.001, R2 = 0.47), the variation in SAA at
      any given intake level was wide. Of the studied patients, 62% had an SAA < 8.7
      mg/L, 40% had an SAA < 5.1 mg/L (below the level in a healthy population), and
      12% had a level below 2 mg/L (scorbutic). None of the patients demonstrated
      clinical manifestations of scurvy. Our results show that, in CAPD patients,
      ascorbic acid deficiency can be reliably detected only with SAA measurements, and
      oral intake may influence SAA level. To maintain ascorbic acid in the normal
      range for healthy adults, daily oral intake needs to be increased above the U.S.
      recommended dietary allowance to 80-140 mg.

PMID- 11510280
TI  - Serum ascorbic acid and protein calorie malnutrition in continuous ambulatory
      peritoneal dialysis patients.
AB  - Protein calorie malnutrition (PCM) is a major predictor of morbidity and
      mortality in continuous ambulatory peritoneal dialysis (CAPD) patients. Oxidative
      stress has been implicated as a contributory cause. The relative lack of ascorbic
      acid, a plasma antioxidant, has been reported in CAPD patients. We therefore
      examined the correlation between serum ascorbic acid (SAA) and parameters of PCM
      in a cross-sectional study of 50 clinically stable adult CAPD patients. The mean
      age of the study group was 61 +/- 11 years; 48% of the patients were male; and
      64% had diabetes. The parameters assessed were SAA, serum albumin (S Alb), body
      mass index (BMI), subjective global assessment (SGA), and lean body mass (LBM).
      The results (mean +/- standard deviation) were: SAA, 9.44 +/- 8.79 mg/L; S Alb,
      31.6 +/- 4.9 g/L; BMI, 24.4 +/- 3.4; LBM, 0.66 +/- 0.14 kg/kg body weight; SGA, 9
      of 50 were considered mildly-to-moderately malnourished (the rest were well
      nourished). A significant correlation (p < 0.001) was found between SAA and S Alb
      only with SAA < or = 9 mg/L. No correlation was seen between SAA (at any level)
      and BMI or LBM. The SAA was not significantly different between the groups as
      graded by SGA. The data suggest that the mechanisms for low serum albumin in
      these patients may be related to the role of ascorbic acid as a plasma
      antioxidant.

PMID- 11510281
TI  - Zinc as a marker of nutrition in continuous ambulatory peritoneal dialysis
      patients.
AB  - Our aim was to show, in continuous ambulatory peritoneal dialysis (CAPD)
      patients, the relationships between zinc (serum level and dietary intake) and
      adequacy and duration of CAPD, age, and measures of nutrition. Serum zinc (12.2
      +/- 1.8 mumol/L) was not significantly related to dietary zinc intake (9.9 +/-
      2.5 mg daily), but depended on daily instilled (r = -0.331, p < 0.05) and
      effluent (r = -0.311, p < 0.05) dialysate volumes and on patient age (r = -0.304,
      p < 0.05). Positive correlations were seen between serum zinc level and
      laboratory (but not anthropometric) markers of nutrition: prealbumin (r = 0.349,
      p < 0.05), iron (r = 0.447, p < 0.05), transferrin saturation [(TSAT) r = 0.374,
      p < 0.05]. Additionally, zinc intake was positively related to serum ferritin
      level (r = 0.370, p < 0.05). Serum zinc level positively influenced blood
      morphology [correlation with hemoglobin (r = 0.287, p < 0.05) and mean
      corpuscular hemoglobin concentration (r = 0.361, p < 0.05)]. Zinc intake showed
      negative correlations with serum levels of total cholesterol (r = -0.373, p <
      0.05) and vitamin E (r = -0.504, p < 0.05), and a positive correlation with HDL:
      total cholesterol ratio (r = 0.338, p < 0.05). Mean values of three latter
      parameters were out of the normal limits (total cholesterol: 219.2 +/- 47.0
      mg/dL; vitamin E: 1.91 +/- 0.82 mg/dL; HDL: total cholesterol ratio: 16.7 +/-
      5.1). We conclude that, in CAPD patients, zinc is a marker of nutrition showing
      beneficial effect on serum iron parameters, blood morphology, lipid profile, and
      elevated vitamin E concentration. Zinc supplementation is needed for
      approximately 16% of CAPD patients, especially older patients and those requiring
      higher dialysate volumes.

PMID- 11510282
TI  - Adequacy and nutrition in the absence of residual renal function in peritoneal
      dialysis.
AB  - With the aim of evaluating nutrition indices and dialysis adequacy level in
      patients who started peritoneal dialysis (PD) without residual renal function, we
      retrospectively studied 19 patients [8 men, 11 women; 3 with diabetes (15.8%);
      mean age: 44.5 +/- 10.74 years; 15 on continuous ambulatory peritoneal dialysis
      (CAPD), 3 on continuous cycling peritoneal dialysis (CCPD), 1 on nightly
      intermittent peritoneal dialysis (NIPD)]. The mean time spent by these patients
      on hemodialysis before PD was 62.7 +/- 54.7 months (range: 8.8-216 months), and
      the mean time on PD was 46.2 +/- 21.4 months (range: 10-75 months). In these
      patients, we measured weekly Kt/V urea, weekly creatinine clearance (CrC),
      normalized protein catabolic rate (nPCR), body surface area (BSA), urea
      distribution volume (V), serum albumin, body mass index (BMI), percent lean body
      mass (%LBM), infusion volume (liters per day), subjective global assessment
      (SGA), and peritoneal equilibration test (PET). Using the Student t-test at a
      significance level of p < 0.05, we compared initial body weight (INW), actual
      weight (AW), and ideal body weight (IBW) according to age, sex, and height. We
      analyzed actuarial and technique survival (Kaplan-Meier). In regard to patient
      survival, only death was considered the end point; for technique survival, only
      technique failure was considered the end point. Data are expressed as mean +/-
      standard deviation. Results were: Kt/V, 2.20 +/- 0.46 L weekly; CrC, 59.11 +/- 12
      L weekly; nPCR, 1.08 +/- 0.25 g/kg daily; BSA, 1.67 +/- 0.2 m2; V, 33.34 +/-
      7.12; serum albumin, 3.68 +/- 0.22 g/dL; BMI, 24.06 +/- 4.16; %LBM, 64.92 +/-
      10.13; SGA, 94.7% well-nourished; AW, 65.37 +/- 13.88 kg; IBW, 67.21 +/- 10.5 kg
      (AW vs IBW: r = 0.69, p > 0.05); INW, 61.54 +/- 11.07 kg (INW vs AW: r = 0.92, p
      < 0.05; INW vs IBW: r = 0.71, p < 0.05). Distribution of transport status by PET
      was 15.8% high transport, 36.8% high-average transport, 36.8% low-average
      transport, and 10.5% low transport. Mean infusion volume was 10.41 +/- 1.36 L in
      24 hours. Cumulative survival was 100%, 98%, and 82% after 1, 2, and 6 years
      respectively. Technique survival was 100% after 6 years. The adequacy results
      accord with Dialysis Outcomes Quality Initiative (DOQI) recommendations, and the
      nutrition indices and actuarial and technique survival are satisfactory for
      anuric patients.

PMID- 11510283
TI  - Acid-base balance and nutrition in peritoneal dialysis.
AB  - Acidosis has been implicated in increased protein catabolism and malnutrition of
      dialysis. The present study examines the effect of acid-base balance on the
      nutrition status of peritoneal dialysis (PD) patients. We followed 43 PD patients
      for one year. Blood chemistries were measured monthly. Patients were divided on
      the basis of subjective global assessment (SGA) into well-nourished (A), mildly
      to-moderately malnourished (B), and severely malnourished (C) groups. Mean serum
      bicarbonate and albumin concentrations were, for group A (n = 16), 23.5 mmol/L
      and 3.96 g/dL respectively; for group B (n = 17), 27.2 mmol/L and 3.50 g/dL
      respectively; and for group C (n = 10), 25.9 mmol/L and 2.9 g/dL respectively. In
      group A, mean serum bicarbonate was significantly lower, and albumin
      concentration significantly higher as compared with the other groups.
      Interestingly, of 9 patients with serum HCO3 < 22 mmol/L, 6 were in group A and 2
      were in group B. Of 6 patients with serum HCO3 > 29 mmol/L, 5 were in group B and
      4 were in group C. The data suggest that well-nourished PD patients tend to be
      more acidotic. Malnutrition in alkalotic PD patients may be due to low protein
      intake resulting in decreased acid production; however, an effect of alkalosis on
      protein metabolism cannot be excluded.

PMID- 11510284
TI  - Low serum albumin in elderly continuous ambulatory peritoneal dialysis patients
      is attributable to high permeability of peritoneum.
AB  - Our study was carried out to investigate changes in nutrition and individual
      peritoneal membrane transport characteristics in elderly patients on continuous
      ambulatory peritoneal dialysis (CAPD), expressed as the personal dialysis
      capacity (PDC). We performed 376 PDC tests in 229 non diabetic patients who were
      undergoing CAPD from May 1995 to May 1999 in a multicenter study in Japan. We
      divided the patients into three groups: elderly (age > or = 65 years, n = 56),
      middle-aged (age 50-65 years, n = 150), and young (age < 50, n = 170). No
      significant differences were seen in duration of CAPD and incidence of
      peritonitis between the groups. We then compared the peritoneal function
      calculated by PDC test in the groups. Serum levels of albumin in elderly patients
      were significantly lower than those in middle-aged and young patients (elderly:
      3.2 +/- 0.1; middle-aged: 3.4 +/- 0.1, p = 0.0447 vs elderly; young: 3.4 +/- 0.1,
      p = 0.0272 vs elderly). Plasma protein loss from the peritoneum in elderly
      patients was significantly higher than in middle-aged and young patients
      (elderly: 0.11 +/- 0.01; middle-aged: 0.09 +/- 0.01, p = 0.0136 vs elderly;
      young: 0.09 +/- 0.01, p = 0.0161 vs elderly). No significant differences in
      ultrafiltration volume and water permeability were seen between the groups.
      Peritoneal area in the elderly group was significantly higher than in the middle
      aged and young groups. Peritoneal creatinine clearance (CCr) and Kt/V in elderly
      patients were significantly higher than in middle-aged and young patients.
      However, no significant difference in protein nitrogen appearance (PNA) or
      protein catabolic rate (PCR) was seen between the groups. Urea and creatinine
      generation rates in elderly patients were significantly lower than in the middle
      aged and young patients. These data show that elderly patients receiving CAPD are
      well maintained from the perspective of urea and water metabolism, indicating
      that CAPD therapy for the elderly is more acceptable than expected. However,
      caution should be exercised, owing to the lower serum albumin seen in elderly
      patients.

PMID- 11510285
TI  - The relationship between dialysate protein loss and membrane transport status in
      peritoneal dialysis patients.
AB  - Peritoneal dialysis (PD) patients lose significant quantities of protein and
      albumin during the dialysis procedure. The losses are greater in high
      transporters. The aim of the present study was to investigate the relationship
      between peritoneal membrane transport characteristics and protein losses. We
      studied 33 PD patients [14 men, 19 women; mean age: 53.5 years (range: 21-80
      years)]. Fourteen patients had diabetes, and 22 were on automated PD. Dialysis
      adequacy was good, with a mean Kt/V of 2.63 (range: 1.51-4.89). Patients
      underwent a standard peritoneal equilibration test (PET). In addition, dialysate
      albumin (Alb) and protein (Pro) were measured at 0, 1, 2, and 4 hours, after lack
      of interference from unspent dialysate was ensured. Of the 33 patients, 23 were
      high or high-average transporters [based on 4-hour dialysate-to-plasma ratio of
      creatinine (D/PCr > or = 0.65)]. Protein losses owing to PD ranged from 3.5 g/day
      to 13.2 g/day (median: 5.9 g/day), of which 1.9-7.14 g/day (median: 3.21 g/day)
      was albumin. The 4-hour D/PCr correlated with the 4-hour D/PAlb (r = 0.62, p <
      0.01), and 4-hour D/PPro (r = 0.63, p < 0.01). This finding persisted after
      correction for volume, indicating that it was not simply a concentration effect.
      The 4-hour D/PAlb and 4-hour D/PPro also correlated with the 24-hour PD albumin
      and protein losses. These results suggest a strong association between D/PCr and
      D/P for proteins. This observation is consistent with the increased protein
      losses through PD in high transporters and may be related to the inferior
      outcomes in this group.

PMID- 11510286
TI  - Use of tissue plasminogen activator for thrombolysis in occluded peritoneal
      dialysis catheters in children.
AB  - Peritoneal dialysis is often the renal replacement therapy of choice in pediatric
      patients, but the smaller catheters are at high risk for occlusion by fibrin
      clots. Tissue-type plasminogen activator (t-PA) is a recombinant protease
      specific for fibrin, and has been shown to be an effective thrombolytic for
      central venous catheters. The present study aimed to demonstrate the
      effectiveness of t-PA for thrombolysis in occluded peritoneal catheters. Six
      patients between 3 weeks and 15 years of age presented with 7 episodes of
      occluded peritoneal catheters. In all cases, t-PA (2 mg in 40 mL normal saline)
      was instilled into the catheter. Patency was assessed after 60 minutes by rapid
      instillation and drainage of 10 mL dialysis solution per kilogram patient body
      weight. Thrombolysis was effective in 4 of 7 attempts. In 2 cases, occlusion
      occurred in the setting of acute peritonitis. In 2 cases, catheters required
      surgical replacement. One child developed a leak at the catheter exit site within
      24 hours after treatment. No intraperitoneal bleeding was observed, and no
      changes were observed in systemic coagulation indices [prothrombin time (PT),
      activated partial thromboplastin time (aPTT), fibrinogen degradation products
      (FDP), and fibrinogen] assessed pre- and post-thrombolysis. In cases of occluded
      PD catheters, t-PA appears to be an effective and safe treatment.

PMID- 11510287
TI  - Recent advances in peritoneal morphology: the milky spots in peritoneal dialysis.
AB  - Milky spots are submesothelial lymphoid structures, essential for the maturation
      of resident peritoneal macrophages, for peritoneal defense, and for all
      peritoneal inflammatory and immune processes. We evaluated the number and size of
      milky spots in omentum of rats subjected to dialysis for 15, 30, and 60 days and
      in omentum of non dialyzed control rats (5 rats per group). After 15 days of
      dialysis, the number (4.2 +/- 1.5/cm2) and mean size (0.13 +/- 0.04 mm2) of milky
      spots were significantly lower than in the control group (7.6 +/- 2.3/cm2, p <
      0.03; 0.25 +/- 0.04 mm2, p < 0.01). After 30 days of dialysis, values returned to
      a level similar to that in controls (6.8 +/- 1.9/cm2 and 0.20 +/- 0.04 mm2).
      After 60 days of dialysis, values were significantly greater than in all other
      groups (11.8 +/- 2.2/cm2 and 0.41 +/- 0.07 mm2, p < 0.03). The early decrease in
      milky spots seems to be due to washing of the peritoneum and replacement of
      resident white cells at the expense of the white cell population in the milky
      spots. At 30 days, a process of adaptation seems to establish functional
      equilibrium. The increase in milky spots after 60 days of dialysis may be due to
      the chronic inflammatory stimulus of dialysis solutions with poor
      biocompatibility.

PMID- 11510288
TI  - Delayed compared with immediate use of peritoneal catheter in pediatric
      peritoneal dialysis.
AB  - Delayed use of the peritoneal catheter may be one method of reducing catheter
      related complications in chronic peritoneal dialysis (PD); however, the risks and
      benefits of immediate as compared with delayed use have not been examined in
      children. We retrospectively analyzed 33 peritoneal catheter placements in 27
      children between 1997 and 2000. Eleven catheters were used for PD immediately
      following insertion (group I); 22 catheters were used only after a delay
      averaging 20 days (group D). Characteristics of the children in the two groups
      were similar. Catheter-related complications within the first 3 months after
      placement--including dialysate leak, fibrin plug, outflow obstruction, cuff
      extrusion, herniation, exit-site and tunnel infection, peritonitis, and catheter
      revision and replacement--were evaluated. Rates of individual complications in
      the two groups were similar, but several trends were noted. Dialysate leaks were
      more common in group I (rate of 0.36 in group I vs 0.09 in group D), and
      infectious complications were more common in group D (rate of exit-site or tunnel
      infection of 0.14 in group D vs 0.09 in group I; rate of peritonitis of 0.36 in
      group D vs 0.18 in group I). We conclude from this small study that delayed use
      of the peritoneal catheter does not appear to convey significant advantages over
      immediate use; however, immediate use may be associated with more frequent
      dialysate leaks. On the other hand, delayed use may be associated with a greater
      risk of infection. Further studies involving larger numbers of children will be
      necessary to confirm these findings.

PMID- 11510289
TI  - Impact of total body water errors on Kt/V estimates in children on peritoneal
      dialysis.
AB  - Determining Kt/V in peritoneal dialysis (PD) requires estimation of total body
      water (TBW). The Dialysis Outcomes Quality Initiative (DOQI) guidelines recommend
      use of the Mellits and Cheek (MC) formulas for the estimation of TBW in children.
      However, the MC formulas were developed from healthy children and may not apply
      to children on PD. Re-evaluating the MC data with additional, recent data from
      healthy infants has led to the development of new formulas. In addition, and as
      part of a prospective study of children initiating PD, the Pediatric Peritoneal
      Dialysis Study Consortium (PPDSC) has directly measured TBW using H2[18O]. To
      assess the impact of various TBW estimates, KPDt/V values prospectively collected
      in 24 children were calculated using H2[18O]-measured TBW (O18), MC-derived TBW
      (MCD), and new-formula TBW (NEW). The mean weekly KPDt/V by O18 was 2.2; by MCD,
      it was 2.0; and by NEW, it was 2.0. The results derived using the O18 method
      varied from both the MCD and the NEW results (p < 0.001). The mean deviation from
      the measured KPDt/V using O18 was 9.5% (maximum: 16%) using the MCD estimate and
      7.8% (maximum: 18%) using the NEW formulas. Determinations of KPDt/V are
      significantly affected by the method of estimating TBW. The PPDSC formulas for
      children on PD based on the use of H2[18O] offer the most accurate means of
      calculating TBW and should replace formulas derived from healthy children. The
      use of Kt/V itself as a marker of adequacy in children will be validated only in
      prospective studies.

PMID- 11510290
TI  - A multicenter survey on automated peritoneal dialysis prescription in children.
AB  - Automated peritoneal dialysis (APD) is considered the first-choice chronic
      peritoneal dialysis modality for pediatric patients. Nighttime APD courses reduce
      the impact of PD treatment on a patient's and family's way of life, and the wide
      range of prescription options permit the dialysis schedule to be tailored to the
      needs of children of varying age and body size. We registered data concerning the
      dialytic regimens adopted in 12 pediatric dialysis centers for the treatment of
      110 children on APD. Of the 110 children, 64 (aged 7.6 +/- 5.1 years) were on
      nightly intermittent peritoneal dialysis (NIPD); 29 (aged 9.2 +/- 4.3 years) were
      on tidal peritoneal dialysis (TPD); and 17 (aged 8.2 +/- 4.9 years) were on
      continuous cycling peritoneal dialysis (CCPD). The main prescription parameters
      for the various regimens (mean +/- standard deviation) were these: NIPD-
      exchanges: 13.0 +/- 5.8; duration: 10.0 +/- 1.1 hours; dwell volume: 36.5 +/- 6.2
      mL/kg body weight (BW); glucose concentration: 1.69% +/- 0.41%. TPD--exchanges:
      23.3 +/- 8.1; duration: 10.0 +/- 1.0 hours; dwell volume: 36.1 +/- 5.9 mL/kg BW;
      glucose concentration: 1.63% +/- 0.37%. CCPD--exchanges: 13.0 +/- 4.7; duration:
      10.1 +/- 1.3 hours; dwell volume: 37.7 +/- 5.2 mL/kg BW; glucose concentration:
      1.65% +/- 0.28%. Tidal volume was 52.2% +/- 9.0% of initial fill volume. Daytime
      dwell volume was 54.8% +/- 17.3% of night volume in CCPD patients, and 56.6% +/-
      13.3% in 9 patients on continuous TPD. Because the patient population in this
      report varied in age, body size, and metabolic needs, the resulting range in
      prescription parameters was quite wide. Nevertheless, the duration of nightly PD
      sessions averaged 10 hours, fill volume averaged 36 mL per kilogram body weight,
      and daytime volume averaged 50% of nighttime fill volume.

PMID- 11510291
TI  - Effects of automated peritoneal dialysis on residual daily urinary volume in
      children.
AB  - Preservation of residual renal function (RRF) is an important goal. In children,
      a more rapid decline in RRF has been observed under hemodialysis (HD) therapy as
      compared with peritoneal dialysis (PD) therapy. In adults, however, automated
      peritoneal dialysis (APD) may cause a more rapid decline of RRF than continuous
      ambulatory peritoneal dialysis (CAPD) does. The objective of the present study, a
      survey in a single center over the last 15 years, was to assess the impact of APD
      versus hemodiafiltration (HDF) on daily urinary volume (dUV) outcome. We included
      97 children who were dialyzed for at least a 12-month period between January 1985
      and December 1999, using either HDF (n = 60; 62%) or PD [n = 37; 38% (86% of
      those on APD)]. The endpoint was anuria occurrence, defined as a dUV below 50
      mL/m2 body surface area (BSA) at three consecutive monthly determinations.
      Despite the use of HDF as hemodialysis therapy (that is, biocompatible membranes
      and a very low incidence of vascular instability during ultrafiltration), PD-
      even predominantly prescribed as APD--was associated with better preservation of
      residual dUV. At dialysis end, anuria occurred in 65% of the children undergoing
      HD as compared with 23% of those undergoing PD. The mean age of the children at
      dialysis start was lower in the PD group. No other significant differences were
      noted between the groups, either for the rate of uropathies or for the RRF at
      initiation of dialysis.

PMID- 11510292
TI  - Factors modulating cytosolic calcium. Role in lipid metabolism and cardiovascular
      morbidity and mortality in peritoneal dialysis patients.
AB  - Studies in the uremic rat indicate that insulin resistance and glucose
      intolerance leading to dyslipidemia are associated with a hyperparathyroid
      induced increase in cytosolic calcium ([Ca++i]). These alterations are reversed
      with verapamil, but recur after discontinuation of the drug, suggesting that
      increased [Ca++i] is responsible for the metabolic derangement. To our knowledge,
      no similar studies have been conducted in humans. We retrospectively examined,
      over 12-year period, the effects of factors that lower [Ca++i] on total serum
      cholesterol and triglycerides in 176 peritoneal dialysis (PD) patients. Because
      the study was retrospective, detailed lipid profiles were not available. We
      therefore relied on the morbidity and mortality outcome related to
      atherosclerotic vascular disease. Diabetic patients were excluded from the study,
      because their dyslipidemia and vascular disease are mediated via a different
      mechanism. The patients were classified into four groups. Group I [high
      parathyroid hormone (PTH) in the absence of calcium channel blockers (CCBs), n =
      56] represented the highest [Ca++i]. Group II (high PTH in the presence of CCBs,
      n = 43) and group III (lower PTH in the absence of CCBs, n = 37) represented
      intermediate [Ca++i]. Group IV (lower PTH in the presence of CCBs, n = 40)
      represented the lowest [Ca++i]. High PTH was defined as > or = 3.0 times normal;
      lower PTH, as < 3.0 times normal. Lower [Ca++i] was achieved through the use of
      CCBs, or through lower PTH, or both. Lower PTH was achieved by parathyroidectomy
      or calcitriol administration. The four groups showed no differences in age, sex,
      race, weight, dialysis duration, or primary disease. Group I showed a mean serum
      cholesterol of 358 +/- 27 mg/dL and serum triglycerides of 469 +/- 41 mg/dL.
      Group II showed mean serum cholesterol of 198 +/- 21 mg/dL and serum
      triglycerides of 147 +/- 17 mg/dL. Group III showed a mean serum cholesterol of
      205 +/- 20 mg/dL and serum triglycerides of 174 +/- 16 mg/dL. Group IV showed
      mean serum cholesterol of 184 +/- 10 mg/dL (p = 0.008) and serum triglycerides of
      103 +/- 8 mg/dL (p = 0.005). The cardiovascular morbidity and mortality
      incidences were: group I, 64%; group II, 27%; group III, 31%; and group IV, 20%
      (p = 0.002). We conclude that, in non diabetic PD patients, dyslipidemia is
      related to a hyperparathyroid-induced increase in cytosolic calcium [Ca++i].
      Lowering [Ca++i] by decreasing the parathormone level (via parathyroidectomy or
      calcitriol administration), or by blocking calcium entry into cells (via CCBs),
      or both, is associated with less dyslipidemia and improved long-term morbidity
      and mortality related to atherosclerotic vascular disease.

PMID- 11510293
TI  - Effect of bicarbonate/lactate peritoneal dialysis solutions on human mesothelial
      cell proliferation ex vivo.
AB  - Peritoneal membrane suffers structural and functional changes over time on
      peritoneal dialysis (PD)--in part, owing to the dialysis solutions currently
      used. Low pH seems to be an important element associated with solution
      bioincompatibility. Bicarbonate-containing fluids open new perspectives on this
      issue. The present study compared the effects of bicarbonate/lactate (Bic/Lac)
      solution (25 mmol/L bicarbonate, 15 mmol/L lactate) and lactate (Lac) solution
      (40 mmol/L lactate) on mesothelial cell (MC) growth in culture. Eight stable PD
      patients were asked to collect peritoneal effluent from an 8-hour dwell on two
      separate days, within an interval shorter than one week. For the first dwell, Lac
      solution was infused; for the second dwell, Bic/Lac solution was instilled. Human
      MCs were isolated from the effluent, seeded in 25-cm2 tissue culture flasks, and
      grown ex vivo. Morphology of the cells was also evaluated. In all effluents, MCs
      were present in mean amounts of 26,939 +/- 21,267 cells (Bic/Lac) and 25,986 +/-
      15,286 cells [Lac, p = nonsignificant (NS)]. Morphology of the MCs was similar
      with both solutions (87.5% typical). After initial culture, MCs from 6 patients
      using Bic/Lac (75%) and 3 patients using Lac (37.5%) reached confluence. At this
      time, the number of MCs from the 3 patients who showed MC growth with both
      solutions was slightly higher with Bic/Lac-buffered fluid (Lac: 1,154,125 +/-
      213,333 cells; Bic/Lac: 1,198,291 +/- 806,713 cells). To summarize: 3 patients
      showed MC growth under both solutions; 3 patients showed MC growth only under
      Bic/Lac solution; and 2 patients showed no MC growth at all. After cells were
      seeded in 24-well plates, the MC growth curve was performed in 4 cases of Bic/Lac
      solution use and in 3 cases of Lac solution use. Although no significant
      differences were observed between the solutions, the final number of MCs obtained
      was higher with Bic/Lac solution use. In conclusion, MCs released into peritoneal
      effluent under bicarbonate/lactate-buffered peritoneal dialysis solution are
      associated with a greater ex vivo proliferation capacity than those released
      under lactate solution in the same patient. This finding may demonstrate better
      biocompatibility for Bic/Lac solution.

PMID- 11510294
TI  - A comparison of the biocompatibility of phosphate-buffered saline and dianeal
      3.86% in the rat model of peritoneal dialysis.
AB  - Phosphate-buffered saline (PBS), an isotonic solution with a physiologic pH can
      be considered an example of a biocompatible dialysis fluid. This study compared
      the biocompatibility of PBS with that of Dianeal 3.86% (Baxter Healthcare
      Corporation, Deerfield, IL, U.S.A.), using a model of peritoneal dialysis in the
      rat. In an acute experiment, after catheter implantation, rats were infused on
      day 1 with PBS, on day 5 with standard dialysis solution (Dianeal 3.86%), and on
      day 7 again with PBS. When rats were injected with Dianeal 3.86%, the
      inflammatory reaction was suppressed as compared with PBS. The cell count was
      lower with Dianeal (-85%, p < 0.001), the neutrophil:macrophage ratio in
      dialysate was 80% lower (p < 0.01), total protein concentration in the Dianeal
      dialysate was 73% lower (p < 0.01), and the dialysate nitrite level was 45% lower
      (p < 0.01). In a chronic experiment, after catheter implantation, rats were
      dialyzed for four weeks with PBS or with Dianeal 3.86%. At the end of the study,
      a 1-hour peritoneal equilibration test (PET) was performed. As evaluated on a
      semiquantitative scale, macroscopic changes in the peritoneum were more severe in
      rats exposed to PBS than in those exposed to Dianeal 3.86% (8.6 +/- 3.2 vs 5.2 +/
      2.6, p < 0.05). The thickness of the visceral peritoneum was comparable in both
      groups; but, in PBS-treated rats, the peritoneal interstitium contained more
      inflammatory cells and more new vessels. During the 1-hour PET, peritoneal
      permeability to water and solutes was comparable in the two groups. Despite a
      more physiologic composition, PBS is a less biocompatible peritoneal dialysis
      solutions than is standard, acidic, hypertonic dialysis solution.

PMID- 11510295
TI  - Hyperosmotic stimuli induces recruitment of aquaporin-1 to plasma membrane in
      cultured rat peritoneal mesothelial cells.
AB  - Aquaporin-1 (AQP-1) has been reported to play an important role in peritoneal
      dialysis. To determine the precise mechanism involved, we used cultured rat
      peritoneal mesothelial cells (RPMCs) to examine the translocation of AQP-1 to the
      plasma membrane induced by hyperosmotic stimuli. Cultured RPMCs obtained from
      male Sprague-Dawley rats were incubated at room temperature in Dulbecco modified
      Eagle medium/F12 (DMEM/F12) with and without glucose or mannitol as the
      hyperosmotic stimulus. The plasma membrane was then extracted by the Percoll
      gradient method. Finally, the abundance AQP-1 molecules in the membrane fraction
      was determined by Western blot analysis. Significant enhancement of AQP-1
      abundance (p < 0.05) was observed within 2.5 minutes of the addition of 5%
      glucose to the medium. The increase was sustained in its abundance through 15
      minutes. Abundance of AQP-1 was also increased (p < 0.05) by the addition of 5%
      mannitol. These results suggest that hyperosmotic stimuli could generate
      increased AQP-1 abundance in the plasma membrane by translocation of AQP-1
      protein from recycling endosomes or early endosomes to the plasma membrane,
      rather than by protein synthesis via newly expressed mRNA. The latter mechanism
      would be expected to take more time.

PMID- 11510296
TI  - Parathyroid hormone contributes to variations in blood morphology in diabetic and
      non diabetic patients treated with continuous ambulatory peritoneal dialysis.
AB  - The present study looked for variations in blood morphology between diabetic
      patients (group I, n = 7) and non diabetic patients (group II, n = 16) treated
      with continuous ambulatory peritoneal dialysis (CAPD). A subsequent trial sought
      to find a reason for discrepancies in the results between the two groups. The
      patients in both groups and similar ages, CAPD durations, and erythropoietin
      dosages. Nutrition, CAPD adequacy, serum iron and ferritin levels, total iron
      binding capacity (TIBC), transferrin saturation (TSAT), red blood cells (RBCs),
      mean corpuscular hemoglobin (MCH), mean corpuscular volume (MCV), mean
      corpuscular hemoglobin concentration (MCHC), hemoglobin (Hb), hematocrit (Hct),
      white blood cells (WBCs), total lymphocyte count (TLC), platelets (PLTs), and
      serum intact parathyroid hormone (PTH) were evaluated every three months. The
      mean result of each parameter was obtained in every patient as representative for
      the entire CAPD course. Means and standard deviations for all respective
      parameters were then calculated for the two groups and compared. In patients with
      diabetes as compared with patients without diabetes, significantly higher numbers
      of RBCs, WBCs, and PLTs were seen, as were higher values for Hb and Hct and a
      lower serum PTH concentration. Values for WBCs, PLTs, and MCH obtained in all
      patients (n = 23) were correlated with serum intact PTH (r = -0.520, p = 0.011; r
      = -0.422, p = 0.045; and r = -0.436, p = 0.037 respectively). When data obtained
      in the patients receiving erythropoietin were excluded and the correlation
      analysis was repeated for the 10 remaining patients, a correlation between serum
      PTH and RBCs was found (r = -0.685, p = 0.029). With comparable age, renal
      function, nutrition, erythropoietin dosage, iron indices, and CAPD adequacy,
      duration, and outcome, higher parameters of blood morphology in diabetic patients
      may be related to lower levels of serum intact PTH, indicating no or only mild
      secondary hyperparathyroidism. Patients with diabetes usually show smaller
      disturbances in PTH level than do non diabetic uremic patients on CAPD. Better
      peripheral morphology indices in the group with diabetes can be expected when
      other factors affecting hematologic status are similar.

PMID- 11510297
TI  - Peritoneal dialysis solutions disturb the balance of apoptosis and proliferation
      of peritoneal cells in chronic dialysis model.
AB  - The present study investigated variation in apoptosis and proliferation, and the
      balance between apoptosis and proliferation, for peritoneal mesothelial cells
      (MCs) after exposure to peritoneal dialysis solution (PDS) in vivo. We implanted
      32 male Sprague-Dawley rats (4 groups; n = 8 in each group) with catheters and
      intraperitoneally infused the animals with 20 mL Dianeal 1.36%, 2.27%, or 3.86%
      (Baxter Healthcare Corporation, Deerfield, IL, U.S.A.) PDS twice daily for eight
      consecutive weeks, using saline as a control. At the end of the eighth week,
      samples of peritoneal membrane were fixed and sliced. Expression of apoptosis was
      checked with TUNEL kits (Boehringer Mannheim, Mannheim, Germany), and expression
      of proliferative cell nuclear antigen (PCNA) was checked by immunohistochemistry
      [streptoavidin-biotin-peroxidase complex (SABC) method]. The ratio of MC
      apoptosis to proliferation was measured from the same slices using the dual-stain
      combination of TUNEL and SABC. Cells positive for apoptosis and PCNA were counted
      for all samples by light microscopy in 50 consecutive grids (10 x by 40).
      Peritoneal dialysis solution was found to significantly induce MC apoptosis as
      compared with control at the end of the eighth week. The degree of apoptosis was
      proportional to the concentration of glucose in the PDS. The 1.36% PDS, but not
      the 2.27% or 3.86%, significantly stimulated the expression of PCNA. The degree
      of PCNA expression was negatively related to the glucose concentration of the
      PDS. The MC apoptosis: PCNA ratio was significantly higher for 3.86% and 2.27%
      PDS than for the control, but no significant difference was seen between 1.36%
      PDS and control. We conclude that glucose-based PDS may induce apoptosis and
      disturb the balance of MC apoptosis and proliferation, and that 1.36% PDS damages
      the balance less than does 2.27% or 3.86% PDS. These effects may be partly due to
      pH, calcium, hyperosmolality, and glucose degradation products (GDPs). Loss of
      balance between MC proliferation and apoptosis--induced by unphysiologic PDS--may
      be one of the major causes of peritoneal membrane failure during long-term
      continuous ambulatory peritoneal dialysis.

PMID- 11510298
TI  - Loss of phospholipids asymmetry in red blood cells contributes to anemia in
      uremic patients.
AB  - Anemia is common in dialysis patients. Change in phospholipids asymmetry in red
      blood cells (RBCs) may affect the removal of RBCs from the circulation and thus
      shorten the lifespan of RBCs. In the present study, we investigated phospholipids
      asymmetry in RBCs in uremic patients and its relationship with anemia. We studied
      34 continuous ambulatory peritoneal dialysis (CAPD) patients (age: 51 +/- 15
      years), 73 hemodialysis (HD) patients (age: 48 +/- 12 years), 8 pre-dialysis
      renal-failure patients (age: 42 +/- 21 years), and 16 healthy controls (age: 32
      +/- 9 years). All patients were clinically stable. Phospholipids asymmetry as
      measured by phosphatidylserine exposure was determined by a flow-cytometric
      annexin V-binding assay. Hemoglobin levels were 93 +/- 20 g/L, 83 +/- 17 g/L, 78
      +/- 21 g/L, and 145.8 +/- 12.5 g/L for CAPD patients, pre-dialysis patients, HD
      patients, and healthy controls respectively. Phosphatidylserine exposure in RBCs
      was significantly higher in uremic patients as compared with healthy controls,
      especially in HD patients--whose values were significantly higher than values
      seen in CAPD patients and pre-dialysis patients. No significant difference was
      seen in RBC phosphatidylserine exposure between pre-dialysis patients and CAPD
      patients. Cells positive for annexin V binding were 1.58%, 1.40%, 2.11%, and
      0.71% for CAPD patients, pre-dialysis patients, HD patients, and healthy controls
      respectively. Significant reverse correlations were seen between annexin V and
      hemoglobin (r = -0.381, p < 0.001), and between annexin V and hematocrit (r = 
      0.355, p < 0.001). Our results suggest that (1) anemia is common in our uremic
      patients, especially in HD patients; and (2) anemia in uremic patients may be
      partly related to the loss of phospholipids asymmetry in RBCs.

PMID- 11510299
TI  - Methods to improve the preservation of peritoneal tissues.
AB  - Peritoneal mesothelial cells are easily detached during conventional tissue
      processing, which may result in artifacts in peritoneal tissue examination.
      Therefore, in the present study, we investigated several methods to improve the
      preservation of the anterior parietal peritoneal tissues. Peritoneal tissue from
      the anterior abdominal wall was taken from each of 5 rats killed for the
      experiment. Tissue samples were immediately treated by one of these methods: (1)
      fixed with 10% formaldehyde; (2) fixed with Bouin's solution; (3) fixed with
      Helly's solution. After fixation, the samples were dehydrated with one of (a)
      ethanol, 1 hour in each step; (b) ethanol, 15 minutes in each step; or (c)
      tertiarybutyl alcohol. Five sections were taken from each tissue and stained with
      hematoxylin and eosin. The quality of tissue fixation was evaluated by image
      analysis. Peritoneal mesothelial cells were well preserved after fixation with
      Helly's solution or Bouin's solution. With 10% formaldehyde, about 40% of the
      mesothelial cells were lost. Dehydration with ethanol--especially long-duration
      dehydration--increased the loss. However, dehydration with tertiarybutyl alcohol
      avoided the increased loss of mesothelial cells. The submesothelial extracellular
      matrix was well preserved with Bouin's solution, but not with the other
      fixatives. Our results suggest that fixation with formaldehyde and dehydration
      with ethanol results in significant loss of peritoneal mesothelial cells and
      submesothelial extracellular matrix in peritoneal tissues. Fixation with Bouin's
      solution and dehydration with tertiary-butyl alcohol may be a better method of
      preserving peritoneal tissue.

PMID- 11510300
TI  - Sodium sulfite and N-acetylcysteine: new additives to dialysate for inhibiting
      formation of glucose degradation products and advanced glycation end-products.
AB  - The present study evaluated the inhibiting effect of various chemicals on the
      advanced glycation end-product (AGEs) cross-linking caused in protein by glucose
      degradation products (GDPs). We evaluated a few dozen organic and inorganic
      chemicals--in addition to previously reported AGE inhibitors, such as thiazolium
      derivatives and aminoguanidine--for their inhibiting effect. Collagen IV (from
      human placenta) or human serum albumin (HSA) was incubated with an AGE
      accelerator and one of the selected chemicals in phosphate buffer solution at 37
      degrees C for as long as 14 days. Fluorescence intensity (440 nm) was determined
      after a given incubation time. Among 36 chemicals tested, 8 new chemicals and 5
      previously known AGE inhibitors significantly suppressed the increase in
      fluorescence intensity seen after incubation of HSA with methylglyoxal. We
      believe that 6 chemicals may effectively quench GDPs and inhibit AGE cross-link
      formation, in a manner different from that of aminoguanidine and thiazolium.

PMID- 11510302
TI  - Disagreement between height/weight classifications of underweight, normal weight,
      and obesity in peritoneal dialysis patients.
AB  - Peritoneal dialysis (PD) patients are classified as underweight, normal weight,
      or obese by height/weight indices including body mass index (BMI) and the body
      weight/desired weight (W/DW) ratio. We compared these classifications of degree
      of obesity in 378 women and 555 men on PD. We used these cut-off values: for
      underweight, BMI < or = 18.5 and W/DW < or = 0.9; for obesity, BMI > or = 30.0
      and W/DW > or = 1.2. The W/DW values were calculated assuming first a small
      frame, then a medium frame, and finally a large frame for all subjects.
      Regardless of sex or skeletal frame, BMI correlated highly with W/DW (r value
      between 0.98 and 0.99); however, the range of BMI values corresponding by linear
      regression to the normal range of W/DW (0.9-1.2) was narrower than the range of
      "normal" BMI (18.5-30.0). Consequently, regardless of sex or skeletal frame,
      smaller fractions of the patient population were classified as underweight or
      obese by BMI standards than by W/DW standards. The degree of agreement of the
      classifications of subjects as underweight, normal weight, or obese by BMI and
      W/DW was evaluated by Cohen's kappa ratio. The kappa ratio varied between 0.47
      and 0.58, indicating a reasonable--but not high--degree of agreement beyond
      chance. The highest kappa ratios were obtained assuming a medium skeletal frame
      for both women and men. Substantial discrepancies are observed in the
      classification of PD patients as underweight, normal weight, or obese by BMI and
      W/DW. Further research is needed to identify the height/weight index that has the
      strongest association both with clinical outcomes and with other, more precise
      measurements of body fat content.

PMID- 11510301
TI  - Evaluation of drainage times and alarms with various automated peritoneal
      dialysis modalities.
AB  - This paper assesses the variation in total drainage time (TDT) and number of
      alarms due to low drainage volume (LDV) in automated peritoneal dialysis (APD)
      patients with varying catheter performance. Catheter performance was measured by
      drainage break point (DBP) in a supine position. Six patients with DBP > or = 80%
      underwent three types of APD: non tidal, 50% tidal, and 80% tidal. Six patients
      with DBP < 70% underwent two types of APD: non tidal and tidal fixed at 5% below
      DBP. In every case, the fill volume was 2.3 L. For the purpose of the study, each
      treatment was continued for seven consecutive nights. Home Choice Pro (Baxter
      Healthcare Corporation, Deerfield, Illinois, U.S.A.) was used to calculate the
      TDT and LDV. With both the non tidal and tidal treatments, TDT was higher in
      patients with DBP < 70% as compared with patients with DBP > or = 80%. In the
      latter group, 50% tidal was the most effective technique in reducing TDT. In
      patients with DBP < 70%, the tidal treatment reduced not only TDT, but also LDV
      alarms, as compared to the non tidal treatment. In conclusion, choosing the tidal
      method helps to reduce LDV alarms and TDT, especially in patients with a low DBP.
      The Home Choice Pro device is an effective aid in setting up and assessing the
      dialytic prescription.

PMID- 11510303
TI  - Hyperinsulinism reduction associated with icodextrin treatment in continuous
      ambulatory peritoneal dialysis patients.
AB  - Glucose absorption from peritoneal dialysis solutions causes a chronic
      stimulation of insulin secretion, which leads to hyperinsulinism. The use of
      solutions without glucose should correct this metabolic derangement together with
      the associated cardiovascular risk. To verify this hypothesis, we studied the
      entire non diabetic continuous ambulatory peritoneal dialysis (CAPD) population
      of our center: 27 patients with a mean age of 62 +/- 15 years, and a median 17
      months on treatment. Morning fasting serum insulin was 32.8 +/- 9.3 microU/mL;
      glucose, 104.4 +/- 21.8 mg/dL; triglycerides, 162.4 +/- 125.7 mg/dL; cholesterol,
      221.9 +/- 54.7 mg/dL; intact parathyroid hormone (iPTH), 212 +/- 189 pg/mL;
      fibrinogen, 519 +/- 112 mg/dL; body mass index, 24.1 +/- 4.1; and daily
      erythropoietin subcutaneous therapy dose, 17 +/- 6 U/kg. Insulin sensitivity,
      measured as ISI-HOMA (insulin sensitivity index, derived from the homeostasis
      model assessment) was 2.4 +/- 0.7. Daily glucose load, calculated from dialytic
      schedules, was 135 +/- 38 g. Of the 27 patients, 12 were treated with standard
      glucose solutions during the day and with one icodextrin dwell during the night
      for a median of 9 months (range: 1-28). The remaining 15 patients were treated
      with standard glucose solutions. The icodextrin group showed significantly lower
      serum insulin levels (28.6 +/- 6.0 microU/mL vs 36.1 +/- 10.2 microU/mL, p =
      0.021) and significantly higher ISI-HOMA values (2.7 +/- 0.5 vs 2.2 +/- 0.7, p =
      0.041) than the control group. The two groups showed no significant differences
      for glucose, triglycerides, cholesterol, iPTH, fibrinogen, body mass index, or
      erythropoietin therapy dose. Daily glucose load was lower in the icodextrin
      group, but without reaching statistical significance (128 +/- 31 g vs 142 +/- 43
      g). This study shows, in a preliminary way, that the chronic use of icodextrin in
      the long nighttime dwell can reduce serum insulin levels and increase insulin
      sensitivity in CAPD patients.

PMID- 11510304
TI  - Sustaining continuous ambulatory peritoneal dialysis after herniotomy.
AB  - Controversy still exists as to whether peritoneal dialysis (PD) treatment can be
      safely continued after herniotomy. Many nephrologists withhold PD treatment for
      several weeks after herniotomy for fear of dialysate leakage and hernia
      recurrence. Here, we report on 9 patients (2 women, 7 men) in whom herniotomy was
      performed for umbilical (n = 3), inguinal (n = 5), or cicatricial hernia (n = 2),
      or for open processus vaginalis (n = 2). Surgery was performed according to the
      Lichtenstein method with insertion of a polypropylene mesh and ligation of the
      hernia sac. In all patients, PD treatment was paused for the day of surgery and
      for 1-3 days postoperatively, depending on residual renal function. Over the next
      several days, low-volume (1.0-1.5 L), high-frequency (6 per day) exchanges were
      started. The patient's original PD regimen was gradually reinstated over the next
      2-4 weeks. All patients recovered rapidly, with no uremia or dialysis-related
      complications. Particularly, no leakage and no hernia recurrence could be
      observed 3 months thereafter. None of the patients had to be hemodialyzed
      intercurrently. In conclusion, continuing a modified regimen of CAPD treatment
      after herniotomy seems to be safe, with excellent patient comfort.

PMID- 11510305
TI  - Cost-effectiveness of peritoneal dialysis catheter implantation by laparoscopy
      versus by open dissection.
AB  - This study evaluates the cost-effectiveness of laparoscopic implantation of
      peritoneal dialysis (PD) catheters as compared with insertion by open dissection.
      The cost analysis was based on clinical experience with 232 consecutive implants
      and 23 procedures to rescue catheters from flow dysfunction. Institutional
      expenses were calculated from the costs of labor and of disposable and reusable
      materials. Payer costs were taken from Medicare reimbursement schedules for
      outpatient, inpatient, professional, and ancillary services. A break-even
      percentage was calculated, representing the point at which the laparoscopic
      procedure became cost-effective because of a lower incidence of costly catheter
      rescue procedures. An observed difference in the incidence of catheter
      obstruction between laparoscopic and open procedures exceeding this percentage
      would indicate that the laparoscopic approach was cost effective. The calculated
      break-even value varied between 1.5% and 26% depending on whether the procedures
      were performed exclusively on an inpatient or outpatient basis. Given our
      inpatient/outpatient case mix, a weighted calculation of the break-even value was
      9.4%. The observed difference in incidence between the two implant methods was
      10.8% overall and 16.4% for the last 91 consecutive laparoscopic procedures. The
      analysis demonstrates that our laparoscopic implantation procedure is a cost
      effective means of establishing PD access as compared with the open dissection
      technique.

PMID- 11510306
TI  - Abdominal catastrophe: definition and proposal for a new approach.
AB  - Abdominal catastrophe, defined as peritonitis from a visceral source, occurs in a
      significant number of patients treated by peritoneal dialysis. Peritonitis due to
      visceral injury is difficult to manage and is associated with high morbidity and
      mortality. Surgical intervention for both diagnosis and repair is definitive.
      However, no preventive strategy has been identified to date. The experience at
      University Hospitals of Cleveland and the published experiences of many other
      centers demonstrate that the risk of this complication has not changed in
      parallel with the many other improvements in the technique and outcome of
      peritoneal dialysis. We propose an approach to improve the understanding and
      outcome of this devastating complication. First, classification of peritonitis by
      source, not by organism, may lead to a more focused response to each episode of
      peritonitis. Second, the importance of antibiotic prophylaxis should be re
      assessed in defined clinical settings that have a high likelihood of progressing
      to abdominal catastrophe. Third, optimal antibiotic regimens need to be devised
      and applied when visceral injury is highly suspected as a cause of peritonitis.
      Finally, the results of surgical interventions must be carefully studied.

PMID- 11510307
TI  - Bag exchange in continuous ambulatory peritoneal dialysis without use of a face
      mask: experience of five years.
AB  - This article describes our five-year experience of continuous ambulatory
      peritoneal dialysis (CAPD) with bag exchanges performed without use of a face
      mask. The study took place in the renal unit at a university hospital. All
      patients admitted to the CAPD program from February 1995 to March 2000 were
      trained to perform bag exchanges without use of a face mask. Occurrence of
      peritonitis episodes was the outcome of interest. We evaluated 94 patients (52
      women, 42 men) with a mean age of 48 +/- 21 years and a total follow-up of 50,502
      patient-days. During that time, 79 episodes of peritonitis occurred in 46
      patients, for a peritonitis rate of 0.57 episodes/year. The most frequently
      isolated micro-organisms were Staphylococcus epidermidis in 20 patients (25.3%)
      and S. aureus in 11 patients (13.9%). Renal transplantation was the major cause
      of drop-out [23 patients (43.4%)], followed by peritonitis [14 patients (26.4%)],
      death due to cardiovascular complications [9 patients (17.0%)], loss of
      ultrafiltration [2 patients (3.8%)], and other causes [5 patients (9.4%)]. The
      probability of being free of peritonitis at 12 months was 0.60, and at 60 months,
      0.37. Peritonitis rates during the study period were not different from those
      reported by other centers, supporting the hypothesis that routine use of a face
      mask during CAPD bag exchange may be unnecessary.

PMID- 11510308
TI  - Cross-cultural adaptation and psychometric evaluation of the Childhood Health
      Assessment Questionnaire (CHAQ) and the Child Health Questionnaire (CHQ) in 32
      countries. Review of the general methodology.
AB  - The aim of this project was to cross-culturally adapt and validate the American
      English version of the Childhood Health Assessment Questionnaire (CHAQ) and of
      the Child Health Questionnaire (CHQ) in the 32 different member countries of the
      Paediatric Rheumatology International Trials Organisation (PRINTO). This effort
      forms part of an international study supported by the European Union to evaluate
      the health-related quality of life in children with juvenile idiopathic arthritis
      (JIA) as compared to their healthy peers. A total of 6,644 subjects were enrolled
      from 32 countries: Argentina, Austria, Belgium, Brazil, Bulgaria, Chile, Croatia,
      the Czech Republic, Denmark, Finland, France, Georgia, Germany, Greece, Hungary,
      Israel, Italy, Korea, Latvia, Mexico, the Netherlands, Norway, Poland, Portugal,
      Russia, Slovakia, Spain, Sweden, Switzerland, Turkey, the United Kingdom, and
      Yugoslavia. A total of 3,235 patients had JIA (20% systemic onset, 33%
      polyarticular onset, 17% extended oligoarticular subtype, and 30% persistent
      oligoarticular subtype) while 3,409 were healthy children. This introductory
      paper describes the methodology used by all the participants. The results and the
      translated version of both the CHAQ and the CHQ for each country are fully
      reported in the following papers. The results of the present study show that
      cross-cultural adaptation is a valid process to obtain reliable instruments for
      the different socio-economic and socio-demographic conditions of the countries
      participating in the project.

PMID- 11510309
TI  - The Argentinian version of the Childhood Health Assessment Questionnaire (CHAQ)
      and the Child Health Questionnaire (CHQ).
AB  - We report herein the results of the cross-cultural adaptation and validation into
      the Argentinian language of the parent's version of two health related quality of
      life instruments. The Childhood Health Assessment Questionnaire (CHAQ) is a
      disease specific health instrument that measures functional ability in daily
      living activities in children with juvenile idiopathic arthritis (JIA). The Child
      Health Questionnaire (CHQ) is a generic health instrument designed to capture the
      physical and psychosocial well-being of children independently from the
      underlying disease. The Argentinian CHAQ was already published and therefore it
      was revalidated while the Argentinian CHQ was derived from the European Spanish
      version by changing few words which use is different in the 2 countries. A total
      of 124 subjects were enrolled: 61 patients with JIA (29% systemic onset, 38%
      polyarticular onset, 7% extended oligoarticular subtype, and 26% persistent
      oligoarticular subtype) and 63 healthy children. The CHAQ clinically
      discriminated between healthy subjects and JIA patients, with the systemic onset,
      and polyarticular having a higher degree of disability, pain, and a lower overall
      well-being when compared to their healthy peers. Also the CHQ clinically
      discriminated between healthy subjects and JIA patients, with the systemic onset,
      polyarticular onset and extended oligoarticular subtypes having a lower physical
      and psychosocial well-being when compared to their healthy peers. In conclusion
      the Argentinian version of the CHAQ-CHQ is a reliable, and valid tool for the
      functional, physical and psychosocial assessment of children with JIA.

PMID- 11510310
TI  - The Latvian version of the Childhood Health Assessment Questionnaire (CHAQ) and
      the Child Health Questionnaire (CHQ).
AB  - We report herein the results of the cross-cultural adaptation and validation into
      the Latvian language of the parent's version of two health related quality of
      life instruments. The Childhood Health Assessment Questionnaire (CHAQ) is a
      disease specific health instrument that measures functional ability in daily
      living activities in children with juvenile idiopathic arthritis (JIA). The Child
      Health Questionnaire (CHQ) is a generic health instrument designed to capture the
      physical and psychosocial well-being of children independently from the
      underlying disease. The Latvian CHAQ CHQ were fully validated with 1 forward and
      1 backward translations. A total of 141 subjects were enrolled: 80 patients with
      JIA (16% systemic onset, 32.5% polyarticular onset, 19% extended oligoarticular
      subtype, and 32.5% persistent oligoarticular subtype) and 61 healthy children.
      The CHAQ clinically discriminated between healthy subjects and JIA patients, with
      the systemic, polyarticular and extended oligoarticular subtypes having a higher
      degree of disability, pain, and a lower overall well-being when compared to their
      healthy peers. Also the CHQ clinically discriminated between healthy subjects and
      JIA patients, with the systemic onset, polyarticular onset and extended
      oligoarticular subtypes having a lower physical and psychosocial well-being when
      compared to their healthy peers. In conclusion the Latvian version of the CHAQ
      CHQ is a reliable, and valid tool for the functional, physical and psychosocial
      assessment of children with JIA.

PMID- 11510311
TI  - The Mexican version of the Childhood Health Assessment Questionnaire (CHAQ) and
      the Child Health Questionnaire (CHQ).
AB  - We report herein the results of the cross-cultural adaptation and validation into
      the Mexican language of the parent's version of two health related quality of
      life instruments. The Childhood Health Assessment Questionnaire (CHAQ) is a
      disease specific health instrument that measures functional ability in daily
      living activities in children with juvenile idiopathic arthritis (JIA). The Child
      Health Questionnaire (CHQ) is a generic health instrument designed to capture the
      physical and psychosocial well-being of children independently from the
      underlying disease. The Mexican CHAQ was already published and therefore it was
      revalidated while the Mexican CHQ was derived from the European Spanish version
      with changing of the few words whose use is different in the 2 countries. A total
      of 182 subjects were enrolled: 89 patients with JIA (26% systemic onset, 47%
      polyarticular onset, 13.5% extended oligoarticular subtype, and 13.5% persistent
      oligoarticular subtype) and 93 healthy children. The CHAQ clinically
      discriminated between healthy subjects and JIA patients, with the systemic onset,
      and polyarticular onset subtypes having a higher degree of disability, pain, and
      a lower overall well-being when compared to their healthy peers. Also the CHQ
      clinically discriminated between healthy subjects and JIA patients, with the
      systemic onset, and polyarticular onset having a lower physical and psychosocial
      well-being when compared to their healthy peers. In conclusion the Mexican
      version of the CHAQ-CHQ is a reliable, and valid tool for the functional,
      physical and psychosocial assessment of children with JIA.

PMID- 11510312
TI  - The Dutch version of the Childhood Health Assessment Questionnaire (CHAQ) and the
      Child Health Questionnaire (CHQ).
AB  - We report herein the results of the cross-cultural adaptation and validation into
      the Dutch language of the parent's version of two health related quality of life
      instruments. The Childhood Health Assessment Questionnaire (CHAQ) is a disease
      specific health instrument that measures functional ability in daily living
      activities in children with juvenile idiopathic arthritis (JIA). The Child Health
      Questionnaire (CHQ) is a generic health instrument designed to capture the
      physical and psychosocial well-being of children independently from the
      underlying disease. The Dutch CHAQ was fully validated with 3 forward and 3
      backward translations while the CHQ was already published and therefore it was
      revalidated. A total of 180 subjects were enrolled: 100 patients with JIA (17%
      systemic onset, 31% polyarticular onset, 18% extended oligoarticular subtype, and
      34% persistent oligoarticular subtype) and 80 healthy children. The CHAQ
      clinically discriminated between healthy subjects and JIA patients, with the
      systemic, polyarticular and extended oligoarticular subtypes having a higher
      degree of disability, pain, and a lower overall well-being when compared to their
      healthy peers. Also the CHQ clinically discriminated between healthy subjects and
      JIA patients, with the systemic onset, polyarticular onset and extended
      oligoarticular subtypes having a lower physical and psychosocial well-being when
      compared to their healthy peers. In conclusion the Dutch version of the CHAQ-CHQ
      is a reliable, and valid tool for the functional, physical and psychosocial
      assessment of children with JIA.

PMID- 11510313
TI  - The Norwegian version of the Childhood Health Assessment Questionnaire (CHAQ) and
      the Child Health Questionnaire (CHQ).
AB  - We report herein the results of the cross-cultural adaptation and validation into
      the Norwegian language of the parent's version of two health related quality of
      life instruments. The Childhood Health Assessment Questionnaire (CHAQ) is a
      disease specific health instrument that measures functional ability in daily
      living activities in children with juvenile idiopathic arthritis (JIA). The Child
      Health Questionnaire (CHQ) is a generic health instrument designed to capture the
      physical and psychosocial well-being of children independently from the
      underlying disease. The Norwegian CHAQ and CHQ have already been published and
      therefore they were fully revalidated in this study. A total of 148 subjects were
      enrolled: 88 patients with JIA (6% systemic onset, 45% polyarticular onset, 10%
      extended oligoarticular subtype, and 39% persistent oligoarticular subtype) and
      60 healthy children. The CHAQ clinically discriminated between patients with
      various JIA subtypes, with the systemic, polyarticular and extended
      oligoarticular subtypes having a higher degree of disability, pain, and a lower
      overall well-being when compared to those with persistent oligoarticular
      arthritis. Also the CHQ clinically discriminated between healthy subjects and JIA
      patients, with the systemic onset, polyarticular onset and extended
      oligoarticular subtypes having a lower physical and psychosocial well-being when
      compared to their healthy peers. In conclusion the Norwegian version of the CHAQ
      CHQ is a reliable, and valid tool for the functional, physical and psychosocial
      assessment of children with JIA.

PMID- 11510314
TI  - The Polish version of the Childhood Health Assessment Questionnaire (CHAQ) and
      the Child Health Questionnaire (CHQ).
AB  - We report herein the results of the cross-cultural adaptation and validation into
      the Polish language of the parent's version of two health related quality of life
      instruments. The Childhood Health Assessment Questionnaire (CHAQ) is a disease
      specific health instrument that measures functional ability in daily living
      activities in children with juvenile idiopathic arthritis (JIA). The Child Health
      Questionnaire (CHQ) is a generic health instrument designed to capture the
      physical and psychosocial well-being of children independently from the
      underlying disease. The Polish CHAQ CHQ were fully validated with 1 forward and 1
      backward translation. A total of 30 subjects were enrolled: 17 patients with JIA
      (35% systemic onset, 18% polyarticular onset, 29% extended oligoarticular
      subtype, and 18% persistent oligoarticular subtype) and 13 healthy children. The
      CHAQ clinically discriminated between healthy subjects and JIA patients, with the
      systemic, polyarticular and extended oligoarticular subtypes having a higher
      degree of disability, pain, and a lower overall well-being when compared to their
      healthy peers. Also the CHQ clinically discriminated between healthy subjects and
      JIA patients, with the systemic onset, polyarticular onset and extended
      oligoarticular subtypes having a lower physical and psychosocial well-being when
      compared to their healthy peers. In conclusion the Polish versions of the CHAQ
      CHQ are reliable, and valid tools for the functional, physical and psychosocial
      assessment of children with JIA.

PMID- 11510315
TI  - The Portuguese version of the Childhood Health Assessment Questionnaire (CHAQ)
      and the Child Health Questionnaire (CHQ).
AB  - We report herein the results of the cross-cultural adaptation and validation into
      the Portuguese language of the parent's version of two health related quality of
      life instruments. The Childhood Health Assessment Questionnaire (CHAQ) is a
      disease specific health instrument that measures functional ability in daily
      living activities in children with juvenile idiopathic arthritis (JIA). The Child
      Health Questionnaire (CHQ) is a generic health instrument designed to capture the
      physical and psychosocial well being of children independently from the
      underlying disease. The Portuguese CHAQ CHQ were fully validated with 3 forward
      and 3 backward translations. A total of 130 subjects were enrolled: 69 patients
      with JIA (32% systemic onset, 19% polyarticular onset, 26% extended
      oligoarticular subtype, and 23% persistent oligoarticular subtype) and 61 healthy
      children. The CHAQ clinically discriminated between healthy subjects and JIA
      patients, with the systemic, polyarticular and extended oligoarticular subtypes
      having a higher degree of disability, pain, and a lower overall well being when
      compared to their healthy peers. Also the CHQ clinically discriminated between
      healthy subjects and JIA patients, with the systemic onset, polyarticular onset
      and extended oligoarticular subtypes having a lower physical and psychosocial
      well being when compared to their healthy peers. In conclusion the Portuguese
      version of the CHAQ-CHQ is a reliable, and valid tool for the functional,
      physical and psychosocial assessment of children with JIA.

PMID- 11510316
TI  - The Russian version of the Childhood Health Assessment Questionnaire (CHAQ) and
      the Child Health Questionnaire (CHQ).
AB  - We report herein the results of the cross-cultural adaptation and validation into
      the Russian language of the parent's version of two health related quality of
      life instruments. The Childhood Health Assessment Questionnaire (CHAQ) is a
      disease specific health instrument that measures functional ability in daily
      living activities in children with juvenile idiopathic arthritis (JIA). The Child
      Health Questionnaire (CHQ) is a generic health instrument designed to capture the
      physical and psychosocial well-being of children independently from the
      underlying disease. The Russian CHAQ CHQ were fully validated with 3 forward and
      3 backward translations. A total of 146 subjects were enrolled: 86 patients with
      JIA (23% systemic onset, 39% polyarticular onset, 15% extended oligoarticular
      subtype, and 23% persistent oligoarticular subtype) and 60 healthy children. The
      CHAQ clinically discriminated between healthy subjects and JIA patients, with the
      systemic, polyarticular and extended oligoarticular subtypes having a higher
      degree of disability, pain, and a lower overall well-being when compared to their
      healthy peers. Also the CHQ clinically discriminated between healthy subjects and
      JIA patients, with the systemic onset, polyarticular onset and extended
      oligoarticular subtypes having a lower physical and psychosocial well-being when
      compared to their healthy peers. In conclusion the Russian version of the CHAQ
      CHQ is a reliable, and valid tool for the functional, physical and psychosocial
      assessment of children with JIA.

PMID- 11510317
TI  - The Slovak version of the Childhood Health Assessment Questionnaire (CHAQ) and
      the Child Health Questionnaire (CHQ).
AB  - We report herein the results of the cross-cultural adaptation and validation into
      the Slovak language of the parent's version of two health related quality of life
      instruments. The Childhood Health Assessment Questionnaire (CHAQ) is a disease
      specific health instrument that measures functional ability in daily living
      activities in children with juvenile idiopathic arthritis (JIA). The Child Health
      Questionnaire (CHQ) is a generic health instrument designed to capture the
      physical and psychosocial well-being of children independently from the
      underlying disease. The Slovak CHAQ CHQ were fully validated with 3 forward and 3
      backward translations. A total of 119 subjects were enrolled: 52 patients with
      JIA (15% systemic onset, 37% polyarticular onset, 10% extended oligoarticular
      subtype, and 38% persistent oligoarticular subtype) and 67 healthy children. The
      CHAQ clinically discriminated between healthy subjects and JIA patients, with the
      systemic, polyarticular and extended oligoarticular subtypes having a higher
      degree of disability, pain, and a lower overall well-being when compared to their
      healthy peers. Also the CHQ clinically discriminated between healthy subjects and
      JIA patients, with the systemic onset, polyarticular onset and extended
      oligoarticular subtypes having a lower physical and psychosocial well-being when
      compared to their healthy peers. In conclusion the Slovak version of the CHAQ-CHQ
      is a reliable, and valid tool for the functional, physical and psychosocial
      assessment of children with JIA.

PMID- 11510319
TI  - The Swedish version of the Childhood Health Assessment Questionnaire (CHAQ) and
      the Child Health Questionnaire (CHQ).
AB  - We report herein the results of the cross-cultural adaptation and validation into
      the Swedish language of the parent's version of two health related quality of
      life instruments. The Childhood Health Assessment Questionnaire (CHAQ) is a
      disease specific health instrument that measures functional ability in daily
      living activities in children with juvenile idiopathic arthritis (JIA). The Child
      Health Questionnaire (CHQ) is a generic health instrument designed to capture the
      physical and psychosocial well-being of children independently from the
      underlying disease. The Swedish CHAQ CHQ were already published and therefore
      were revalidated in this study. A total of 129 subjects were enrolled: 69
      patients with JIA (13% systemic onset, 39% polyarticular onset, 25% extended
      oligoarticular subtype, and 23% persistent oligoarticular subtype) and 60 healthy
      children. The CHAQ clinically discriminated between healthy subjects and JIA
      patients, with the systemic, polyarticular and extended oligoarticular subtypes
      having a higher degree of disability, pain, and a lower overall well-being when
      compared to their healthy peers. Also the CHQ clinically discriminated between
      healthy subjects and JIA patients, with the systemic onset, polyarticular onset
      and extended oligoarticular subtypes having a lower physical and psychosocial
      well-being when compared to their healthy peers. In conclusion the Swedish
      version of the CHAQ-CHQ are reliable, and valid tools for the functional,
      physical and psychosocial assessment of children with JIA.

PMID- 11510318
TI  - The European Spanish version of the Childhood Health Assessment Questionnaire
      (CHAQ) and the Child Health Questionnaire (CHQ).
AB  - We report herein the results of the cross-cultural adaptation and validation of 2
      health related quality of life instruments into the European Spanish language.
      The Childhood Health Assessment Questionnaire (CHAQ) is a disease specific health
      instrument that measures functional ability in daily living activities in
      children with Juvenile Idiopathic Arthritis (JIA). The Child Health Questionnaire
      (CHQ) is a generic health instrument designed to capture the physical and
      psychosocial well-being of children independently from an underlying disease. The
      Spanish CHQ was fully validated with 3 forward and 3 backward translations, while
      the Spanish CHAQ, already published, was revalidated. A total of 149 subjects
      were enrolled: 80 patients with JIA (28% systemic arthritis, 34% polyarthritis,
      17% extended oligoarthritis, and 21% persistent oligoarthritis) and 69 healthy
      children. The CHAQ appropriately distinguished healthy subjects from JIA
      patients, with those classified in the systemic arthritis, polyarthritis and
      extended oligoarthritis categories having a higher degree of disability and pain,
      as well as a lower overall well-being than their healthy peers. The CHQ was also
      able to discriminate healthy subjects from JIA patients, with those allocated in
      the systemic arthritis, polyarthritis and extended oligoarthritis categories
      having a lower physical and psychosocial well-being than their healthy
      counterparts. In conclusion, the European Spanish version of the CHAQ-CHQ is a
      reliable and valid tool for the functional, physical and psychosocial assessment
      of children with JIA.

PMID- 11510320
TI  - The Austrian version of the Childhood Health Assessment Questionnaire (CHAQ) and
      the Child Health Questionnaire (CHQ).
AB  - We report herein the results of the cross-cultural adaptation and validation into
      the Austrian language of the parentis version of two health related quality of
      life instruments. The Childhood Health Assessment Questionnaire (CHAQ) is a
      disease specific health instrument that measures functional ability in daily
      living activities in children with juvenile idiopathic arthritis (JIA). The Child
      Health Questionnaire (CHQ) is a generic health instrument designed to capture the
      physical and psychosocial well-being of children independently from the
      underlying disease. The Austrian CHAQ CHQ were adapted from the German version of
      the CHAQ-CHQ, and revalidated in this study. A total of 134 subjects were
      enrolled: 74 patients with JIA (9.5% systemic onset, 42% polyarticular onset,
      9.5% extended oligoarticular subtype, and 39% persistent oligoarticular subtype)
      and 60 healthy children. The CHAQ clinically discriminated between healthy
      subjects and JIA patients, with the systemic, polyarticular and extended
      oligoarticular subtypes having a higher degree of disability, pain, and a lower
      overall well-being when compared to their healthy peers. Also the CHQ clinically
      discriminated between healthy subjects and JIA patients, with the systemic onset,
      polyarticular onset and extended oligoarticular subtypes having a lower physical
      and psychosocial well-being when compared to their healthy peers. In conclusion
      the Austrian version of the CHAQ-CHQ is a reliable, and valid tool for the
      functional, physical and psychosocial assessment of children with JIA.

PMID- 11510321
TI  - The Swiss German and Swiss French versions of the Childhood Health Assessment
      Questionnaire (CHAQ) and the Child Health Questionnaire (CHQ).
AB  - We report herein the results of the cross-cultural adaptation and validation into
      the Swiss German and Swiss French languages of the parent's version of two health
      related quality of life instruments. The Childhood Health Assessment
      Questionnaire (CHAQ) is a disease specific health instrument that measures
      functional ability in daily living activities in children with juvenile
      idiopathic arthritis (JIA). The Child Health Questionnaire (CHQ) is a generic
      health instrument designed to capture the physical and psychosocial well-being of
      children independently from the underlying disease. The Swiss German and Swiss
      French CHAQ-CHQ were adapted from the German and French versions of the CHAQ-CHQ,
      and revalidated in this study. A total of 147 subjects were enrolled: 85 patients
      with JIA (22% systemic onset, 31% polyarticular onset, 32% extended
      oligoarticular subtype, and 15% persistent oligoarticular subtype) and 62 healthy
      children. The CHAQ clinically discriminated between healthy subjects and JIA
      patients, with the systemic, polyarticular and extended oligoarticular subtypes
      having a higher degree of disability, pain, and a lower overall well-being when
      compared to their healthy peers. Also the CHQ clinically discriminated between
      healthy subjects and JIA patients, with the systemic onset, polyarticular onset
      and extended oligoarticular subtypes having a lower physical and psychosocial
      well-being when compared to their healthy peers. In conclusion the Swiss German
      and Swiss French versions of the CHAQ-CHQ are reliable, and valid tools for the
      functional, physical and psychosocial assessment of children with JIA.

PMID- 11510322
TI  - The Turkish version of the Childhood Health Assessment Questionnaire (CHAQ) and
      the Child Health Questionnaire (CHQ).
AB  - We report herein the results of the cross-cultural adaptation and validation into
      the Turkish language of the parent's version of two health related quality of
      life instruments. The Childhood Health Assessment Questionnaire (CHAQ) is a
      disease specific health instrument that measures functional ability in daily
      living activities in children with juvenile idiopathic arthritis (JIA). The Child
      Health Questionnaire (CHQ) is a generic health instrument designed to capture the
      physical and psychosocial well-being of children independently from the
      underlying disease. The Turkish CHAQ CHQ were fully validated with 3 forward and
      3 backward translations. A total of 145 subjects were enrolled: 85 patients with
      JIA (35% systemic onset, 41% polyarticular onset, and 24% persistent
      oligoarticular subtype) and 60 healthy children. The CHAQ clinically
      discriminated between healthy subjects and JIA patients, with the systemic, and
      polyarticular subtypes having a higher degree of disability, pain, and a lower
      overall well-being when compared to their healthy peers. Also the CHQ clinically
      discriminated between healthy subjects and JIA patients, with the systemic onset,
      and polyarticular onset having a lower physical and psychosocial well-being when
      compared to their healthy peers. In conclusion the Turkish version of the CHAQ
      CHQ is a reliable, and valid tool for the functional, physical and psychosocial
      assessment of children with JIA.

PMID- 11510323
TI  - The British version of the Childhood Health Assessment Questionnaire (CHAQ) and
      the Child Health Questionnaire (CHQ).
AB  - We report herein the results of the cross-cultural adaptation and validation into
      the British language of the parent's version of two health related quality of
      life instruments. The Childhood Health Assessment Questionnaire (CHAQ) is a
      disease specific health instrument that measures functional ability in daily
      living activities in children with juvenile idiopathic arthritis (JIA). The Child
      Health Questionnaire (CHQ) is a generic health instrument designed to capture the
      physical and psychosocial well-being of children independently from the
      underlying disease. A total of 440 subjects were enrolled: 219 patients with JIA
      (17% systemic onset, 41% polyarticular onset, 33% extended oligoarticular
      subtype, and 9% persistent oligoarticular subtype) and 221 healthy children. The
      CHAQ clinically discriminated between healthy subjects and JIA patients, with the
      systemic, polyarticular and extended oligoarticular subtypes having a higher
      degree of disability, pain, and a lower overall well-being when compared to their
      healthy peers. Also the CHQ clinically discriminated between healthy subjects and
      JIA patients, with the systemic onset, polyarticular onset and extended
      oligoarticular subtypes having a lower physical and psychosocial well-being when
      compared to their healthy peers. In conclusion the British version of the CHAQ
      CHQ is a reliable, and valid tool for the functional, physical and psychosocial
      assessment of children with JIA.

PMID- 11510324
TI  - The Serbian version of the Childhood Health Assessment Questionnaire (CHAQ) and
      the Child Health Questionnaire (CHQ).
AB  - We report herein the results of the cross-cultural adaptation and validation into
      the Serbian language of the parentis version of two health related quality of
      life instruments. The Childhood Health Assessment Questionnaire (CHAQ) is a
      disease specific health instrument that measures functional ability in daily
      living activities in children with juvenile idiopathic arthritis (JIA). The Child
      Health Questionnaire (CHQ) is a generic health instrument designed to capture the
      physical and psychosocial well-being of children independently from the
      underlying disease. The Serbian CHAQ-CHQ were fully validated with 3 forward and
      1 backward translations. A total of 139 subjects were enrolled: 79 patients with
      JIA (30% systemic onset, 28% polyarticular onset, 6% extended oligoarticular
      subtype, and 36% persistent oligoarticular subtype) and 60 healthy children. The
      CHAQ clinically discriminated between healthy subjects and JIA patients, with the
      systemic, polyarticular and extended oligoarticular subtypes having a higher
      degree of disability, pain, and a lower overall well-being when compared to their
      healthy peers. Also the CHQ clinically discriminated between healthy subjects and
      JIA patients, with the systemic onset, polyarticular onset and extended
      oligoarticular subtypes having a lower physical and psychosocial well-being when
      compared to their healthy peers. In conclusion the Serbian version of the CHAQ
      CHQ is a reliable, and valid tool for the functional, physical and psychosocial
      assessment of children with JIA.

PMID- 11510325
TI  - The Belgian-Flemish version of the Childhood Health Assessment Questionnaire
      (CHAQ) and the Child Health Questionnaire (CHQ).
AB  - We report herein the results of the cross-cultural adaptation and validation into
      the Belgian-Flemish language of the parent's version of two health related
      quality of life instruments. The Childhood Health Assessment Questionnaire (CHAQ)
      is a disease specific health instrument that measures functional ability in daily
      living activities in children with juvenile idiopathic arthritis (JIA). The Child
      Health Questionnaire (CHQ) is a generic health instrument designed to capture the
      physical and psychosocial well-being of children independently from the
      underlying disease. The Belgian-Flemish CHAQ was fully validated with 3 forward
      and 3 backward translations, while the Belgian-Flemish CHQ was equal to the Dutch
      version and revalidated in this study. The French version of both CHAQ and CHQ
      was exactly the same as the one used in France. A total of 199 subjects were
      enrolled: 53 patients with JIA (11% systemic onset, 40% polyarticular onset, 13%
      extended oligoarticular subtype, and 36% persistent oligoarticular subtype) and
      146 healthy children. The CHAQ clinically discriminated between healthy subjects
      and JIA patients, with the polyarticular onset, and extended oligoarticular
      subtypes having a higher degree of disability, pain, and a lower overall well
      being when compared to their healthy peers. Also the CHQ clinically discriminated
      between healthy subjects and JIA patients, with the polyarticular onset and
      extended oligoarticular subtypes having a lower physical and psychosocial well
      being when compared to their healthy peers. In conclusion the Belgian-Flemish
      version of the CHAQ-CHQ is a reliable, and valid tool for the functional,
      physical and psychosocial assessment of children with JIA.

PMID- 11510326
TI  - The Brazilian version of the Childhood Health Assessment Questionnaire (CHAQ) and
      the Child Health Questionnaire (CHQ).
AB  - We report the cross-cultural adaptation and validation into Brazilian-Portuguese
      of the parent's version of two health related quality of life instruments. The
      Childhood Health Assessment Questionnaire (CHAQ) is a disease specific health
      instrument that measures functional ability in daily living activities in
      children with juvenile idiopathic arthritis (JIA). The Child Health Questionnaire
      (CHQ) is a generic health instrument designed to capture the physical and
      psychosocial well-being of children regardless the underlying disease. The
      Brazilian CHAQ was revalidated, while the CHQ has been derived from the
      Portuguese version. A total of 471 subjects were enrolled: 157 patients with JIA
      (27% systemic onset, 38% polyarticular onset, 9% extended oligoarticular subtype,
      and 26% persistent oligoarticular subtype) and 314 healthy children. The CHAQ
      discriminated clinically healthy subjects from JIA patients, with the systemic,
      polyarticular and extended oligoarticular subtypes having a higher degree of
      disability, pain, and lower overall well-being scores when compared to their
      healthy peers. Also the CHQ discriminated clinically healthy subjects from JIA
      patients, with the systemic onset, polyarticular onset and extended
      oligoarticular subtypes having a lower physical and psychosocial well-being score
      when compared to their healthy peers. In conclusion the Brazilian versions of the
      CHAQ-CHQ are reliable and valid tools for the combined physical and psychosocial
      assessment of children with JIA.

PMID- 11510327
TI  - The Bulgarian version of the Childhood Health Assessment Questionnaire (CHAQ) and
      the Child Health Questionnaire (CHQ).
AB  - We report herein the results of the cross-cultural adaptation and validation into
      the Bulgarian language of the parent's version of two health related quality of
      life instruments. The Childhood Health Assessment Questionnaire (CHAQ) is a
      disease specific health instrument that measures functional ability in daily
      living activities in children with juvenile idiopathic arthritis (JIA). The Child
      Health Questionnaire (CHQ) is a generic health instrument designed to capture the
      physical and psychosocial well-being of children independently from the
      underlying disease. The Bulgarian CHAQ CHQ were fully validated with 1 forward
      and 1 backward translations. 137 subjects were enrolled: 77 patients with JIA
      (36% systemic onset, 30% polyarticular onset, 4% extended oligoarticular subtype,
      and 30% persistent oligoarticular subtype) and 60 healthy children. The CHAQ
      clinically discriminated between healthy subjects and JIA patients, with the
      polyarticular and extended oligoarticular subtypes having a higher degree of
      disability, pain, and a lower overall well-being when compared to their healthy
      peers. Also the CHQ clinically discriminated between healthy subjects and JIA
      patients, with the polyarticular onset and extended oligoarticular subtypes
      having a lower physical and psychosocial well-being when compared to their
      healthy peers. In conclusion the Bulgarian version of the CHAQ-CHQ is a reliable,
      and valid tool for the functional, physical and psychosocial assessment of
      children with JIA.

PMID- 11510328
TI  - The Chilean version of the Childhood Health Assessment Questionnaire (CHAQ) and
      the Child Health Questionnaire (CHQ).
AB  - We report herein the results of the cross-cultural adaptation and validation into
      the Chilean language of the parent's version of two health related quality of
      life instruments. The Childhood Health Assessment Questionnaire (CHAQ) is a
      disease specific health instrument that measures functional ability in daily
      living activities in children with juvenile idiopathic arthritis (JIA). The Child
      Health Questionnaire (CHQ) is a generic health instrument designed to capture the
      physical and psychosocial well-being of children independently from the
      underlying disease. The Chilean CHAQ-CHQ were derived from the European Spanish
      version with changing of the few words whose use is different in the 2 countries.
      A total of 126 subjects were enrolled: 72 patients with JIA (29% systemic onset,
      39% polyarticular onset, 4% extended oligoarticular subtype, and 28% persistent
      oligoarticular subtype) and 54 healthy children. The CHAQ clinically
      discriminated between healthy subjects and JIA patients, with the JIA patients
      having a higher degree of disability, pain, and a lower overall well-being when
      compared to their healthy peers. Also the CHQ clinically discriminated between
      healthy subjects and JIA patients, with the JIA patients having a lower physical
      and psychosocial well-being when compared to their healthy peers. In conclusion
      the Chilean version of the CHAQ-CHQ is a reliable, and valid tool for the
      functional, physical and psychosocial assessment of children with JIA.

PMID- 11510329
TI  - The Croatian version of the Childhood Health Assessment Questionnaire (CHAQ) and
      the Child Health Questionnaire (CHQ).
AB  - We report herein the results of the cross-cultural adaptation and validation into
      the Croatian language of the parent's version of two health related quality of
      life instruments. The Childhood Health Assessment Questionnaire (CHAQ) is a
      disease specific health instrument that measures functional ability in daily
      living activities in children with juvenile idiopathic arthritis (JIA). The Child
      Health Questionnaire (CHQ) is a generic health instrument designed to capture the
      physical and psychosocial well-being of children independently from the
      underlying disease. The Croatian CHAQ-CHQ were fully validated with 3 forward and
      3 backward translations. A total of 139 subjects were enrolled: 75 patients with
      JIA (19% systemic onset, 20% polyarticular onset, 17% extended oligoarticular
      subtype, and 44% persistent oligoarticular subtype) and 64 healthy children. CHAQ
      clinically discriminated between healthy subjects and JIA patients, with the
      polyarticular and extended oligoarticular subtypes having a higher degree of
      disability, pain, and a lower overall well-being when compared to their healthy
      peers. Also the CHQ clinically discriminated between healthy subjects and JIA
      patients, with the polyarticular onset and extended oligoarticular subtypes
      having a lower physical and psychosocial well-being when compared to their
      healthy peers. In conclusion the Croatian version of the CHAQ-CHQ is a reliable,
      and valid tool for the functional, physical and psychosocial assessment of
      children with JIA.

PMID- 11510330
TI  - The Czech version of the Childhood Health Assessment Questionnaire (CHAQ) and the
      Child Health Questionnaire (CHQ).
AB  - We report herein the results of the cross-cultural adaptation and validation into
      the Czech language of the parent's version of two health related quality of life
      instruments. The Childhood Health Assessment Questionnaire (CHAQ) is a disease
      specific health instrument that measures functional ability in daily living
      activities in children with juvenile idiopathic arthritis (JIA). The Child Health
      Questionnaire (CHQ) is a generic health instrument designed to capture the
      physical and psychosocial well-being of children independently from the
      underlying disease. The Czech CHAQ-CHQ were fully validated with 3 forward and 3
      backward translations. A total of 150 subjects were enrolled: 81 patients with
      JIA (14% systemic onset, 44% polyarticular onset, 10% extended oligoarticular
      subtype, and 32% persistent oligoarticular subtype) and 69 healthy children. The
      CHAQ clinically discriminated between healthy subjects and JIA patients, with the
      systemic, polyarticular and extended oligoarticular subtypes having a higher
      degree of disability, pain, and a lower overall well-being when compared to their
      healthy peers. Also the CHQ clinically discriminated between healthy subjects and
      JIA patients, with the systemic onset, polyarticular onset and extended
      oligoarticular subtypes having a lower physical and psychosocial well-being when
      compared to their healthy peers. In conclusion the Czech version of the CHAQ-CHQ
      is a reliable, and valid tool for the functional, physical and psychosocial
      assessment of children with JIA.

PMID- 11510331
TI  - The Danish version of the Childhood Health Assessment Questionnaire (CHAQ) and
      the Child Health Questionnaire (CHQ).
AB  - We report herein the results of the cross-cultural adaptation and validation into
      the Danish language of the parent's version of two health related quality of life
      instruments. The Childhood Health Assessment Questionnaire (CHAQ) is a disease
      specific health instrument that measures functional ability in daily living
      activities in children with juvenile idiopathic arthritis (JIA). The Child Health
      Questionnaire (CHQ) is a generic health instrument designed to capture the
      physical and psychosocial well-being of children independently from the
      underlying disease. The Danish CHAQ-CHQ were fully validated with 3 forward and 3
      backward translations. A total of 139 subjects were enrolled: 76 patients with
      JIA (25% systemic onset, 30% polyarticular onset, 19% extended oligoarticular
      subtype, and 26% persistent oligoarticular subtype) and 63 healthy children. The
      CHAQ clinically discriminated between healthy subjects and JIA patients, with the
      systemic, polyarticular and extended oligoarticular subtypes having a higher
      degree of disability, pain, and a lower overall well-being when compared to their
      healthy peers. Also the CHQ clinically discriminated between healthy subjects and
      JIA patients, with the systemic onset, polyarticular onset and extended
      oligoarticular subtypes having a lower physical and psychosocial well-being when
      compared to their healthy peers. In conclusion the Danish version of the CHAQ-CHQ
      is a reliable, and valid tool for the functional, physical and psychosocial
      assessment of children with JIA.

PMID- 11510332
TI  - The Finnish version of the Childhood Health Assessment Questionnaire (CHAQ) and
      the Child Health Questionnaire (CHQ).
AB  - We report herein the results of the cross-cultural adaptation and validation into
      the Finnish language of the parent's version of two health related quality of
      life instruments. The Childhood Health Assessment Questionnaire (CHAQ) is a
      disease specific health instrument that measures functional ability in daily
      living activities in children with juvenile idiopathic arthritis (JIA). The Child
      Health Questionnaire (CHQ) is a generic health instrument designed to capture the
      physical and psychosocial well-being of children independently from the
      underlying disease. The Finnish CHAQ-CHQ were validated with 3 forward and 1
      backward translations. A total of 161 subjects were enrolled: 89 patients with
      JIA (9% systemic onset, 44% polyarticular onset, 26% extended oligoarticular
      subtype, and 21% persistent oligoarticular subtype) and 72 healthy children. The
      CHAQ clinically discriminated between healthy subjects and JIA patients, with the
      systemic, polyarticular and extended oligoarticular subtypes having a higher
      degree of disability, pain, and a lower overall well-being when compared to their
      healthy peers. Also the CHQ clinically discriminated between healthy subjects and
      JIA patients, with the systemic, polyarticular and extended oligoarticular
      subtypes having a lower physical and psychosocial well-being when compared to
      their healthy peers. In conclusion the Finnish version of the CHAQ-CHQ is a
      reliable and valid tool for the functional, physical and psychosocial assessment
      of children with JIA.

PMID- 11510333
TI  - The French version of the Childhood Health Assessment Questionnaire (CHAQ) and
      the Child Health Questionnaire (CHQ).
AB  - We report the results of the cross-cultural adaptation and validation into the
      French language of two health status instruments. The Childhood Health Assessment
      Questionnaire (CHAQ) is a disease specific instrument that measures functional
      ability in daily living activities in children with juvenile idiopathic arthritis
      (JIA). The Child Health Questionnaire (CHQ) is a generic health related quality
      of life instrument designed to capture the physical and psychosocial well-being
      of children independently from the underlying disease. Five hundred children were
      enrolled including 306 patients with JIA classified into systemic (23%),
      polyarticular (22%), extended oligoarticular (25%), and persistent oligoarticular
      (30%) subtypes, and 194 healthy children. Both instruments were reliable with
      intra-class correlation (ICC) coefficients for the test-retest procedure of 0.91
      for the CHAQ, and 0.87 and 0.89 for the physical and psychosocial summary scores
      of CHQ, respectively. Agreement between parents and children evaluated for the
      CHAQ was high with an ICC of 0.89 for the disability index; weighted kappa
      coefficients for the 8 domains ranged from 0.61 to 0.72. Convergent validity was
      demonstrated by significant correlations with the JIA core set of variables
      (physician and parent global assessment, scores for active joints and joints with
      limited range of motion, erythrocyte sedimentation rate) for both instruments.
      Both CHAQ and CHQ discriminated between healthy and JIA children, but only the
      disease specific CHAQ questionnaire discriminated clearly between the 4 JIA
      subtypes. In conclusion, the French versions of the CHAQ and the CHQ are
      reliable, and valid health assessment questionnaires to be used in children
      suffering from JIA.

PMID- 11510334
TI  - The Georgian version of the Childhood Health Assessment Questionnaire (CHAQ) and
      the Child Health Questionnaire (CHQ).
AB  - We report herein the results of the cross-cultural adaptation and validation into
      the Georgian language of the parent's version of two health related quality of
      life instruments. The Childhood Health Assessment Questionnaire (CHAQ) is a
      disease specific health instrument that measures functional ability in daily
      living activities in children with juvenile idiopathic arthritis (JIA). The Child
      Health Questionnaire (CHQ) is a generic health instrument designed to capture the
      physical and psychosocial well-being of children independently from the
      underlying disease. The Georgian CHAQ CHQ were fully validated with 3 forward and
      3 backward translation. A total of 115 subjects were enrolled: 54 patients with
      JIA (44% systemic onset, 28% polyarticular onset, 7.5% extended oligoarticular
      subtype, and 20.5% persistent oligoarticular subtype) and 61 healthy children.
      The CHAQ clinically discriminated between healthy subjects and JIA patients, with
      the systemic, polyarticular and extended oligoarticular subtypes having a higher
      degree of disability, pain, and a lower overall well-being when compared to their
      healthy peers. Also the CHQ clinically discriminated between healthy subjects and
      JIA patients, with the systemic onset, polyarticular onset and extended
      oligoarticular subtypes having a lower physical and psychosocial well-being when
      compared to their healthy peers. In conclusion the Georgian version of the CHAQ
      CHQ is a reliable, and valid tool for the functional, physical and psychosocial
      assessment of children with JIA.

PMID- 11510335
TI  - The German version of the Childhood Health Assessment Questionnaire (CHAQ) and
      the Child Health Questionnaire (CHQ).
AB  - We report the results of the cross-cultural adaptation and validation into the
      German language of the parent's version of two health related quality of life
      instruments. The Childhood Health Assessment Questionnaire (CHAQ) is a disease
      specific health instrument that measures functional ability in daily living
      activities in children with juvenile idiopathic arthritis (JIA). The Child Health
      Questionnaire (CHQ) is a generic health instrument designed to capture the
      physical and psychosocial well-being of children independently from the
      underlying disease. The German CHAQ was fully validated with 3 forward and 3
      backward translations, while the CHQ has already been published and therefore it
      was revalidated. A total of 197 subjects were enrolled: 142 patients with JIA (5%
      systemic onset, 13% polyarticular onset, 8% extended oligoarticular subtype, and
      74% persistent oligoarticular subtype) and 55 healthy children. The CHAQ
      clinically discriminated between healthy subjects and JIA patients, with the
      polyarticular and extended oligoarticular subtypes having a higher degree of
      disability, pain, and a lower overall well-being when compared to their healthy
      peers. Also the CHQ clinically discriminated between healthy subjects and JIA
      patients, with the polyarticular onset and extended oligoarticular subtypes
      having a lower physical and psychosocial well-being when compared to their
      healthy peers. In conclusion the German versions of the CHAQ-CHQ are reliable,
      and valid tools for the functional, physical and psychosocial assessment of
      children with JIA.

PMID- 11510336
TI  - The Greek version of the Childhood Health Assessment Questionnaire (CHAQ) and the
      Child Health Questionnaire (CHQ).
AB  - We report herein the results of the cross-cultural adaptation and validation into
      the Greek language of the parent's version of 2 health related quality of life
      instruments. The Childhood Health Assessment Questionnaire (CHAQ) is a disease
      specific health instrument that measures functional ability in daily living
      activities in children with juvenile idiopathic arthritis (JIA). The Child Health
      Questionnaire (CHQ) is a generic health instrument designed to capture the
      physical and psychosocial well-being of children independently from the
      underlying disease. The Greek CHAQ CHQ were fully validated with 3 forward and 3
      backward translations. A total of 143 subjects were enrolled: 82 patients with
      JIA (28% systemic onset, 24% polyarticular onset, 10% extended oligoarticular
      subtype, and 38% persistent oligoarticular subtype) and 61 healthy children. The
      CHAQ clinically discriminated between healthy subjects and JIA patients, with the
      systemic, polyarticular and extended oligoarticular subtypes having a higher
      degree of disability, pain, and a lower overall well-being when compared to their
      healthy peers. Also the CHQ clinically discriminated between healthy subjects and
      JIA patients, with the systemic onset, polyarticular onset and extended
      oligoarticular subtypes having a lower physical and psychosocial well-being when
      compared to their healthy peers. In conclusion the Greek version of the CHAQ-CHQ
      is a reliable, and valid tool for the functional, physical and psychosocial
      assessment of children with JIA.

PMID- 11510337
TI  - The Hungarian version of the Childhood Health Assessment Questionnaire (CHAQ) and
      the Child Health Questionnaire (CHQ).
AB  - We report herein the results of the cross-cultural adaptation and validation into
      the Hungarian language of the parent's version of two health related quality of
      life instruments. The Childhood Health Assessment Questionnaire (CHAQ) is a
      disease specific health instrument that measures functional ability in daily
      living activities in children with juvenile idiopathic arthritis (JIA). The Child
      Health Questionnaire (CHQ) is a generic health instrument designed to capture the
      physical and psychosocial well-being of children independently from the
      underlying disease. The Hungarian CHAQ CHQ were fully validated with 3 forward
      and 3 backward translations. A total of 127 subjects were enrolled: 67 patients
      with JIA (13.5% systemic onset, 42% polyarticular onset, 13.5% extended
      oligoarticular subtype, and 31% persistent oligoarticular subtype) and 60 healthy
      children. The CHAQ clinically discriminated between healthy subjects and JIA
      patients, with the systemic, polyarticular and extended oligoarticular subtypes
      having a higher degree of disability, pain, and a lower overall well-being when
      compared to their healthy peers. Also the CHQ clinically discriminated between
      healthy subjects and JIA patients, with the systemic onset, polyarticular onset
      and extended oligoarticular subtypes having a lower physical and psychosocial
      well-being when compared to their healthy peers. In conclusion the Hungarian
      version of the CHAQ-CHQ is a reliable, and valid tool for the functional,
      physical and psychosocial assessment of children with JIA.

PMID- 11510338
TI  - The Hebrew version of the Childhood Health Assessment Questionnaire (CHAQ) and
      the Child Health Questionnaire (CHQ).
AB  - We report herein the results of the cross-cultural adaptation and validation into
      the Hebrew language of the parent's version of two health related quality of life
      instruments. The Childhood Health Assessment Questionnaire (CHAQ) is a disease
      specific health instrument that measures functional ability in daily living
      activities in children with juvenile idiopathic arthritis (JIA). The Child Health
      Questionnaire (CHQ) is a generic health instrument designed to capture the
      physical and psychosocial well-being of children independently from the
      underlying disease. The Hebrew CHAQ-CHQ were fully developed with 3 forward and 3
      backward translations. A total of 144 subjects were enrolled: 80 patients with
      JIA (12% systemic onset, 34% polyarticular onset, 23% extended oligoarticular
      subtype, and 31% persistent oligoarticular subtype) and 64 healthy children. The
      CHAQ clinically discriminated between healthy subjects and JIA patients, with the
      systemic, polyarticular and extended oligoarticular subtypes having a higher
      degree of disability, pain, and a lower overall well-being when compared to their
      healthy peers. Also the CHQ clinically discriminated between healthy subjects and
      JIA patients, with the JIA patients having a lower physical and psychosocial well
      being when compared to their healthy peers. In conclusion the Hebrew version of
      the CHAQ-CHQ is a reliable, and valid tool for the functional, physical and
      psychosocial assessment of children with JIA.

PMID- 11510339
TI  - The Italian version of the Childhood Health Assessment Questionnaire (CHAQ) and
      the Child Health Questionnaire (CHQ).
AB  - We report herein the results of the cross-cultural adaptation and validation into
      the Italian language of the parent's version of two health related quality of
      life instruments. The Childhood Health Assessment Questionnaire (CHAQ) is a
      disease specific health instrument that measures functional ability in daily
      living activities in children with juvenile idiopathic arthritis (JIA). The Child
      Health Questionnaire (CHQ) is a generic health instrument designed to capture the
      physical and psychosocial well-being of children independently from the
      underlying disease. The Italian CHAQ was already published in the literature and
      was therefore revalidated while the Italian CHQ was fully cross culturally
      adapted with 3 forward and 3 backward translations, and than validated. A total
      of 1,192 subjects were enrolled: 404 patients with JIA (16% systemic onset, 31%
      polyarticular onset, 21% extended oligoarticular subtype, and 32% persistent
      oligoarticular subtype) and 788 healthy children. The CHAQ clinically
      discriminated between healthy subjects and JIA patients, with the systemic,
      polyarticular and extended oligoarticular subtypes having a higher degree of
      disability, pain, and a lower overall well-being when compared to their healthy
      peers. Also the CHQ clinically discriminated between healthy subjects and JIA
      patients, with the systemic onset, polyarticular onset and extended
      oligoarticular subtypes having a lower physical and psychosocial well-being when
      compared to their healthy peers. In conclusion the Italian version of the CHAQ
      CHQ are reliable, and valid tools for the functional, physical and psychosocial
      assessment of children with JIA.

PMID- 11510340
TI  - The Korean version of the Childhood Health Assessment Questionnaire (CHAQ) and
      the Child Health Questionnaire (CHQ).
AB  - We report herein the results of the cross-cultural adaptation and validation into
      the Korean language of the parent's version of two health related quality of life
      instruments. The Childhood Health Assessment Questionnaire (CHAQ) is a disease
      specific health instrument that measures functional ability in daily living
      activities in children with juvenile idiopathic arthritis (JIA). The Child Health
      Questionnaire (CHQ) is a generic health instrument designed to capture the
      physical and psychosocial well-being of children independently from the
      underlying disease. A total of 221 subjects were enrolled: 87 patients with JIA
      (18% systemic onset, 37% polyarticular onset, 12% extended oligoarticular
      subtype, and 33% persistent oligoarticular subtype) and 134 healthy children. The
      CHAQ clinically discriminated between healthy subjects and the four JIA subtypes
      of patients, with the JIA patients having a higher degree of disability, pain,
      and a lower overall well-being when compared to their healthy peers. Also the CHQ
      clinically discriminated between healthy subjects and JIA patients, with the JIA
      patients having a lower physical and psychosocial well-being when compared to
      their healthy peers. In conclusion the Korean version of the CHAQ-CHQ is a
      reliable, and valid tool for the functional, physical and psychosocial assessment
      of children with JIA.

PMID- 11510341
TI  - The importance of adenoviral infections in pediatrics.

PMID- 11510342
TI  - Vision screening performed by the pediatrician.

PMID- 11510343
TI  - Eyeglasses: why and when do children need them?

PMID- 11510344
TI  - Management of corneal abrasions and ocular trauma in children.

PMID- 11510345
TI  - Management of strabismus in the first year of life.

PMID- 11510346
TI  - Management of congenital nasolacrimal duct obstruction.

PMID- 11510347
TI  - Pediatric ocular and periocular tumors.

PMID- 11510348
TI  - [Experience in the clinical use of intravenous hypnotic pofol (propofol) in
      anesthesias of different duration].
AB  - A new anesthetic pofol is characterized by predominantly hypnotic effect; it is a
      pharmacological analog of a well-known drug diprivan (propofol). The drug was
      used in 60 anesthesias for bronchoscopic manipulations and cardiosurgical
      operations. Its effects on hemodynamics, gas exchange, and reactions during
      induction and after anesthesia were evaluated. The present findings and results
      of previous clinical trials of diprivan indicate identity of pofol and diprivan.
      Clinical course of induction and anesthesia and hemodynamic reactions and effects
      on the respiratory system of patients were virtually the same. Pofol is well
      tolerated by the patients, its allergenic activity is low, it is rapidly
      metabolized and causes virtually no side effects. Positive results of clinical
      trials of pofol recommend it for clinical use.

PMID- 11510349
TI  - [Electrophysiological evaluation of the efficiency of general anesthesia with the
      use of propofol generics].

PMID- 11510350
TI  - [Clinical and pharmacological characteristics of ropivacaine in sacral
      anesthesia].

PMID- 11510351
TI  - [Clinical experience in the use of epidural blockade in complex anesthesia in
      cardiac surgical interventions].
AB  - A total of 326 patients were operated on the heart under total and combined
      epidural anesthesia. Multicomponent total anesthesia in combination with epidural
      blocking is indicated for patients with coronary disease, aortal and mitral valve
      failure, arterial and pulmonary hypertension. The dose of fentanyl is decreased
      2.98 times, duration of forced ventilation of the lungs 2-fold, and the incidence
      of cardiovascular and pulmonary complications is reduced in patients subjected to
      cardiosurgical interventions under total anesthesia in combination with epidural
      blocking.

PMID- 11510352
TI  - [Noninvasive ventilation of the lungs in the treatment of acute respiratory
      failure in immunocompromised patients].
AB  - The purpose of this study was to evaluate the efficiency and place of noninvasive
      ventilation of the lungs (NVL) in the treatment of hypoxemic acute respiratory
      failure (ARF) in patients with tumorous diseases of the blood. The study was
      carried out in 12 patients (3 men and 9 women) with tumorous diseases of the
      blood system, in whom NVL was used for treating ARF. Central hemodynamic and
      oxygen transport parameters were studied using Swan-Hanz catheter. NVL was
      uneventfully carried out in 5 (41.7%) of 12 patients (group 1). Group 2 consisted
      of 7 patients intubated after the beginning of NVL: 2 had to be transferred to
      forced ventilation of the lungs (FVL) because of loss of consciousness and 5
      because of augmenting severity of ARD. All patients transferred to FVL died.
      During the first 3 h of NVL, oxygen delivery increased from 371.3 +/- 84.9 to
      443.9 +/- 92.7 gm/m2 and oxygen consumption from 123.9 +/- 35.9 to 173.5 +/- 34
      m/m2, oxygen alveolar-arterial difference decreased from 400.8 +/- 165.3 to 210
      +/- 57.5 mm Hg, pulmonary shunt from 41.8 +/- 11.9 to 19 +/- 7.9%, PaO2/FiO2 from
      140.4 +/- 210 +/- 84.9, left-ventricular stroke index increased from 38.2 +/-
      14.9 to 50.6 +/- 21.8 ml/m2, left-ventricular output index from 37 +/- 19.5 to
      47.4 +/- 23.7 gm/m2, and heart rate decreased from 119.2 +/- 17.5 to 111.4 +/-
      23.8 min-1. In group 2 greater fraction of inhaled oxygen and higher positive
      pressure at the end of inspiration were required than in group 1. Heart rate and
      oxygen alveolar-arterial difference were higher in group 2. Side effects of NVL
      were skin maceration, hematomas on the bridge of the nose, and conjunctivitis. A
      specific complication associated with thrombocytopenia was the hemorrhagic
      syndrome (nasal bleeding, hemorrhagic stomatitis). Hence, NVL is the first stage
      of respiratory support in hypoxemic ARF. In immunocompromised patients NVL is
      effective only in cases when the cause of damage to the lung is rapidly diagnosed
      and effective pathogenetic therapy promptly started.

PMID- 11510353
TI  - [Comparative evaluation of different tracheal accesses for artificial ventilation
      of the lungs in patients with depressed hematopoiesis].
AB  - The purpose of this study was to analyze the complications and errors in tracheal
      intubation and tracheostomy, development of algorithm of steps for provision of
      endotracheal access in patients with hematological diseases. Provision of
      endotracheal access in 115 patients with blood system diseases is analyzed
      retrospectively. A total of 113 orotracheal, 50 nasotracheal intubations, and 48
      tracheostomies were carried out. In 6 patients fibrobronchoscope was used for
      intubation because of pronounced hemorrhagic syndrome, inflammatory changes, and
      soft tissue edema of the face and neck; in 2 patients tracheostoma was inserted
      under local anesthesia. In 12 patients nasotracheal intubation was complicated by
      nasal bleeding. The most frequent and serious complication in patients with a
      tube in the trachea was obturation of the tube with sputum (9.7% of orotracheal
      intubations, 30% of nasotracheal intubations, and 15% of tracheostomas).
      Extubation/decannulation was carried out in 20 patients. One patient developed
      cicatricial stenosis of the trachea after tracheostoma. Hemorrhagic
      tracheobronchitis was endoscopically diagnosed most often (in 55 cases). Autopsy
      showed hemorrhages in the mucosa in 68.2%, in soft tissues adjacent to
      tracheostoma in 41.4%, and suppurative inflammation in 15.2% cases. Hence,
      hemorrhagic tracheobronchitis, hemorrhages in the mucosa, soft tissues of the
      trachea and bronchi are the most frequent clinical and morphological
      complications in patients with depressed hemopoiesis. Indications for
      nasotracheal intubation in this patient population should be limited. Early
      tracheostomy is recommended. Algorithm of steps ensuring the patency of airways
      in patients subjected to forced ventilation of the lungs is offered.

PMID- 11510354
TI  - [Post-resuscitation cicatricial stenosis of the trachea: causes, prevention and
      first emergency care].

PMID- 11510355
TI  - [Effects of efferent therapy on the blood oxygen transporting function in diffuse
      suppurative peritonitis in patients with diabetes mellitus].
AB  - Twenty patients with non-insulin-dependent diabetes mellitus were treated in
      intensive care wards for diffuse purulent peritonitis developing during diabetes
      decompensation. Group 1 (10 pts) were treated by basic therapy after surgery, in
      group 2 (10 pts) basic therapy was supplemented by hemoquantum, efferent, and
      oxidative therapy with consideration for endotoxicosis phases. Basic therapy
      during the early postoperative period did not remove disorders in the blood
      oxygen-transporting function, while sessions of hemoquantum, efferent, and
      oxidative therapy supplementing basic therapy with consideration for the phases
      of endotoxicosis improved this function due to decrease of intoxication, diabetes
      compensation, and increase of cardiac output.

PMID- 11510356
TI  - [Blood loss compensation during surgery of abdominal aortic aneurysms].
AB  - Two methods of intraoperative compensation of blood loss in patients with aortic
      aneurysm are compared in 30 patients: transfusion of donor blood preparations and
      reinfusion of washed autoerythrocytes. Changes in hemostasis system, central
      hemodynamics, and oxygen transport were analyzed. Reinfusion of washed
      autoerythrocytes proved to be more safe and involved no serious complications.

PMID- 11510357
TI  - [Role of oxidative stress as a component of critical states in the genesis of
      hemostatic disorders].
AB  - The effect of oxidative stress (OS) on hemostasis parameters was studied in model
      systems Fe(2+)-ascorbic acid-EDTA and Fe(2+)-EDTA-H2O2. Blood recalcification
      time, thrombin time, activated partial thromboplastin time, prothrombin index,
      the content of fibrinogen, antithrombin III, soluble fibrin-monomer complexes,
      platelet count and aggregation activity were evaluated. Parameters characterizing
      the severity of OS were measured: protein concentrations of carbonyl and
      sulfhydryl groups and level of malonic dialdehyde. OS was found to induce changes
      in the hemostasis system, promoting the progress of intravascular coagulation
      during the formation of critical state. The authors conclude that antioxidants
      should be added to combined therapy of blood clotting disorders in critical
      patients.

PMID- 11510358
TI  - [Prehospital stage of care of patients and accident victims with acute
      neurosurgical diseases].
AB  - Prehospital care of victims with craniocerebral injuries and patients with
      cerebrovascular diseases is evaluated by means of retrospective analysis of
      emergency files and case histories of 258 patients with acute neurosurgical
      diseases treated in intensive neurosurgical care wards of N. V. Sklifosovsky
      Institute of Emergency Care. The results evidence that the majority of patients
      were hospitalized in a grave or extremely grave state. Prehospital care was
      inadequate: respiratory support was carried out in only 57% patients and oxygen
      therapy in but 23%, which resulted in pronounced disorders of blood gas
      composition and acid-base status. The highest mortality was observed among
      patients in whom intubation of the trachea was delayed. Prehospital infusion
      therapy was administered to 11% and inotropic support to only 1.1% patients.
      Oxygenation and active infusion therapy are recommended for all patients at the
      prehospital stage of care; indications for intubation of the trachea and
      sympathomimetic therapy should be extended.

PMID- 11510359
TI  - [Effects of basic therapy of ischemic heart disease on vascular-platelet
      hemostasis during myocardial revascularization].
AB  - Effects of preoperative therapy of coronary diseases with calcium antagonists and
      aspirin on vascular platelet hemostasis during aortocoronary shunting (ACS) have
      been studied in order to evaluate the role of hemostasis disorders in the
      pathogenesis of perioperative hemorrhagic complications. Therapy of coronary
      disease with these drugs during preparation to ACS can involve changes in
      platelet functional activity, depending on the individual sensitivity of
      patients. Drug-induced thrombocytopathy can induce pathological hemorrhages in
      the perioperative period of ACS.

PMID- 11510360
TI  - [Tissue hypoxia in acute myocardial infarction and possible approaches to its
      correction].
AB  - Gas exchange values were studied in 94 patients with complicated myocardial
      infarction. The degree of hypoxia correlated with the severity of complications
      during the acute stage of disease, which coincided with disorders in the
      myocardial contractile function. Hyperbaric oxygenation (HBO) in a sparing
      regimen, added to combined therapy of acute myocardial infarction, effectively
      liquidated tissue hypoxia and improved the contractile and pumping function of
      the heart. HBO in combination with antioxidants is the most effective in acute
      myocardial infarction after essential decrease of paO2 and pa-vO2 during the
      early postinfarction period in patients with signs of heart dilatation and
      decreased contractility; in addition, the efficiency of the method depends on the
      pattern of the preinfarction period.

PMID- 11510361
TI  - [Degree of the severity of fat embolism].
AB  - The authors discuss evaluation of the severity of fatty embolism. Three criteria
      are taken into consideration: clinical symptoms, presence of fat in the serum or
      liquor, and presence of fat on the surface of serum or liquor. The broth symptom
      is defined. The studies indicate that after detection of this symptom microscopy
      of the serum for detecting fatty globulemia is inefficient.

PMID- 11510363
TI  - [Clinical experience with the use of gelofusin (gelatin) in anesthesiology,
      resuscitation and intensive care].
AB  - Published reports on the use of colloid plasma substitute gelofusin, widely used
      in practical anesthesiology, intensive care, and resuscitation, are analyzed. The
      drug is characterized by positive effects on the hemodynamic status and oxygen
      transporting function of circulation, with the minimum side effects. It can be
      used for blood loss compensation, planned normovolemic hemodilution, afferent
      procedures, and filling the artificial circulation device. Gelofusin is
      preferable for use in patients with cardiac failure and marked dehydration. No
      negative effect on renal function and blood clotting system, even in infusions in
      high volume, are its positive qualities.

PMID- 11510362
TI  - [Multiple organ failure as a manifestation of immune dysregulation of reparative
      processes in the organs during critical states].
AB  - The authors claim that the specific clinical symptoms of multiple organ failure
      (MOF) are explained by impaired interactions of two functionally related systems:
      the immune system (IS) responsible for regeneration and the reticuloendothelial
      system (RES) responsible for inflammation. Organ regeneration during MOF is
      suppressed as a result of suppressed morphogenetic function of lymphocytes,
      imbalanced macrophage-lymphocyte interactions, and RES hyperactivation. For
      prevention and treatment of MOF, the authors recommend stimulation of reparative
      processes in the organs by splenic therapy: assisted xenospleen, infusion of
      splenic perfusate or xenosplenic peptides. Xenospleen therapy is preferable to
      other methods of immunocorrection due to more expressed morphogenetic activity of
      splenic T lymphocytes and their cytokines.

PMID- 11510364
TI  - [Computer analysis of components of general anesthesia].
AB  - Monitoring of cerebral evoked potentials during total anesthesia provides
      objective data on the depth of anesthesia. Somatosensory and auditory evoked
      potentials (SSEP and AEP, respectively) were recorded in 48 patients (ASA
      physical status 1-2) before and during surgery. AEPs were assessed using a two
      stimulus oddball paradigm under passive ignore conditions. Decreased amplitudes
      and increased latencies of mid-latency SSEP were regarded as decreased conduction
      of pain pulse via specific and nonspecific pathways. The amplitude of late
      latency AEP indicated the level of consciousness during total anesthesia. The
      removal of evoked potentials was followed by development of painful reaction.
      Registration of cerebral evoked potentials helps evaluate the depth of anesthesia
      and intraoperative memory in patients subjected to total anesthesia.

PMID- 11510365
TI  - [Role of nitric oxide (NO) in the mechanism of anesthetic action].
AB  - Published reports on modifications of nitric oxide (NO) synthase (NOS) activity
      and NO production in the brain during development of anesthesia induced by the
      most common inhalational (halothane, isoflurane, sevoflurane, enflurane) and
      intravenous (ketamine, barbiturates, propofol, etomidate) anesthetics are
      reviewed. According to a popular universally acknowledged hypothesis, inhibition
      of NOS activity and blockade of NO neurotransmitter function are important steps
      in the mechanism of action of anesthetics. There are data which confirm the
      validity of this hypothesis for all above-listed drugs, but there are also data
      which disagree with it. Some scientists find that anesthesia has no effect on NOS
      activity and NO production, others found that the enzyme activity and NOS gene
      expression increased under the effect of anesthesia. Published reports and
      authors' data on a drastic increase of NO content in the cerebral cortex in
      halothane anesthesia are discussed. The effects of narcotics on NO-mediated
      changes in vascular tone are analyzed.

PMID- 11510366
TI  - [In memory of A. P. Eremich. The 90th anniversary of "Russian intravenous
      anesthesia"].

PMID- 11510367
TI  - [Anesthesiology in orthotopic liver transplantation: first experience].
AB  - The authors present the first clinical experience gained in anesthesia and
      intensive care during 8 orthotopic transplantations of the liver in 4 male and 4
      female patients aged 24-50 years. Veno-venous bypass for general anesthesia is
      described. hemodynamic, oxygen balance, metabolic and blood clotting parameters
      during anesthesia and surgery are analyzed. Drastic changes were noted during the
      liver-free phase: oxygen delivery and consumption decreased almost twofold, a
      metabolic acidosis was observed before and, more so, during this phase.

PMID- 11510368
TI  - [Libyostrongylus douglassii in ostriches (Struthio camelus ssp.) in the
      Netherlands: case report and review].
AB  - Several types of worms can parasitize ostriches, the most pathogenic of which is
      the wire worm (Libyostrongylus douglassii). This worm, which occurs in the
      stomach, can cause severe lesions which can lead to a high mortality, especially
      among young birds. This article describes mortality due to this parasite on an
      ostrich farm and discusses relevant literature on L. douglassii.

PMID- 11510369
TI  - [Performance indicators of hygiene during animal transportation. Results of a
      large scale monitoring of trucks with ATP-bioluminescent technique].
AB  - From 1997 until 1999 932 animal transport trucks were screened for hygiene. In
      total 6542 samples were investigated using the ATP bioluminescence method. The
      aim was to gain insight into performance indicators that affect truck hygiene.
      Hygiene was significantly better in the trucks of large companies than in the
      trucks of small companies (p < 0.005), in the trucks of animal breeders than in
      the trucks of animal traders and transporters (p < 0.05), and in trucks used to
      transport pigs rather than cattle (p < 0.001). A floor of aluminium was
      significantly more hygienic than a floor made of polyester (p < 0.001). Ambient
      temperature during cleaning and the brand of disinfectant also had a significant
      effect on hygiene.

PMID- 11510370
TI  - [Cooperative veterinarian in search and rescue cases must be well considered].

PMID- 11510371
TI  - [Curious and critical: Dr. Rob Slappendel. 'The blood goes where it can't be'].

PMID- 11510372
TI  - [Regulation of Newcastle disease vaccination. Goal oriented, not compromising].

PMID- 11510373
TI  - [Hypoderma diana in roe deer in the Netherlands].
AB  - An infestation with Hypoderma diana in roe deer in the Netherlands is described.
      The condition of the infested deer was poor. Hypoderma diana is no threat for
      cattle.

PMID- 11510374
TI  - [Cyniclomyces guttulatus and diarrhea in dogs].

PMID- 11510375
TI  - [The killing of aquarium fish by their owners].

PMID- 11510376
TI  - [Unnecessary use of antibiotics. Reaction to 'Interaction of diet and veterinary
      drugs'].

PMID- 11510377
TI  - [Democratic state].

PMID- 11510378
TI  - [Non-vaccine regulation].

PMID- 11510379
TI  - [Veterinarians should not treat against owner's wishes].

PMID- 11510380
TI  - [It is never right! Veterinary disciplinary law].

PMID- 11510381
TI  - [Group Groot Dagen 2000: taking advantage of new changes. The modern agricultural
      veterinarian has integrity, social capacities and is well informed].

PMID- 11510382
TI  - [GVP-code dairy goat husbandry].

PMID- 11510383
TI  - [Regulation of recognition and registration of veterinary specialists.
      Registration commission takes over advice for specialization].

PMID- 11510384
TI  - [Opinion and motion concerning foot and mouth disease].

PMID- 11510385
TI  - [Separating pets from farm animals].

PMID- 11510386
TI  - General practice in an age of measurement.

PMID- 11510387
TI  - Dyspepsia in primary care--to prescribe or to investigate?

PMID- 11510388
TI  - The barriers to effective management of heart failure in general practice.
AB  - BACKGROUND: Several studies have shown that most patients with heart failure are
      not investigated and treated according to published guidelines. More effective
      management could reduce both mortality and morbidity from heart failure. AIM: To
      identify the reasons for gaps between recommended and actual management of heart
      failure in general practice. DESIGN OF STUDY: A nominal group technique was used
      to elicit general practitioners' (GPs') perceptions of the reasons for
      differences between observed and recommended practice. SETTING: Ten Medical
      Research Council General Practice Framework practices in the North Thames region.
      METHOD: Data were collected on the investigation and treatment of heart failure
      in the 10 participating practices and presented to 49 GPs and 10 practice nurses
      from those practices. RESULTS: Of the 674 patients requiring echocardiograms, 226
      were referred for echocardiography (34%), and 183/391 (47%) with probable heart
      failure were prescribed angiotensin-converting enzyme inhibitors. A wide variety
      of barriers were elicited. The main barrier to the use of echocardiograms in the
      diagnosis of heart failure was lack of open access. The main barrier to the use
      of angiotensin-converting enzyme inhibitors in treating heart failure was GPs'
      concerns about their possible adverse effects. CONCLUSION: The barriers to the
      effective management of heart failure in general practice are complex. We
      recommend further research to establish whether multifaceted intervention
      programmes based on our findings can improve the management of heart failure in
      primary care.

PMID- 11510389
TI  - A randomised controlled trial of four management strategies for dyspepsia:
      relationships between symptom subgroups and strategy outcome.
AB  - BACKGROUND: The first step in the management of uncomplicated dyspepsia in
      primary care often consists of prescribing empirical therapy, but in certain
      cases prompt endoscopy might be preferred. Any decision is usually based on the
      patient's symptoms and the presumed underlying pathology that causes these
      symptoms. AIM: To assess the relationship between symptom subgroups and the
      effect of management strategies on primary care patients with dyspepsia. DESIGN
      OF STUDY: Randomised controlled trial. SETTING: All patients presenting
      successively with a new episode of dyspepsia between January 1995 and November
      1997. METHOD: The results of four management strategies in dyspeptic primary care
      patients were compared and the value of subgrouping within this trial was
      estimated. Patients were allocated to one of either (a) empirical treatment in
      which therapy was based on the presented symptoms, or empirical treatment with
      (b) omeprazole or (c) cisapride regardless of the presented symptoms, or (d)
      prompt endoscopy followed by the appropriate treatment. Patients were
      retrospectively classified into the subgroups for each strategy using baseline
      data. The yield of each strategy was measured by counting the number of strategy
      failures in the first year. RESULTS: Of the 349 included patients, 326 were
      analysed. No statistically significant difference could be demonstrated between
      the strategies or between the symptom subgroups. However, patients in the reflux
      like subgroup showed a trend towards a better outcome in all empirical
      strategies. Ulcer-like dyspepsia seemed to benefit from omeprazole. The non
      specific subgroup seemed to benefit from cisapride but also had the highest
      proportion of strategy failure. Prompt endoscopy did not appear especially useful
      in any subgroup. CONCLUSION: Although this study has relatively low power, we
      conclude that the use of symptom subgroups seems to be a sensible approach when
      choosing empirical therapy in dyspepsia. Patients with reflux-like symptoms seem
      to have the best prognosis in the first year in every strategy.

PMID- 11510390
TI  - General practice out-of-hours service, variations in use and equality in access
      to a doctor: a cross-sectional study.
AB  - BACKGROUND: There is increasing dissatisfaction among general practitioners (GPs)
      with their 24 hour commitment despite the demand for GP services outside ordinary
      working hours. The creation of out-of-hours co-operatives has been welcomed by
      participating GPs and their families and patient satisfaction is generally high.
      However, there have been concerns about the lack of patient consultation in their
      development and on the quality of care provided. OBJECTIVES: To examine
      geographical variation in the rates of out-of-hours calls and to see if there is
      any systematic variation in how the co-operative that covers the area responds to
      calls. DESIGN OF STUDY: A secondary data analysis of 110,357 calls received by
      the co-operative during the second year of its operation. SETTING: A co-operative
      with four centres providing out-of-hours care for one mostly rural Health Board
      in Northern Ireland. METHOD: Deprivation score and mortality and long-term
      illness ratios provided indicators of need at an area level. Proximity to the
      four co-operative centres was measured as the distance in kilometres and
      estimated travel time (in minutes) along the road network. RESULTS: Out-of-hours
      call ratios were proportional to the area deprivation score and proximity to the
      co-operative centres, though not to area indicators of ill health. Older patients
      were more likely to be seen by the GP and females over the age of 15 years were
      more likely to receive telephone advice only (adjusted odds ratio [OR] = 0.785,
      95% confidence intervals [CI] 0.756-0.816, P < 0.001). Each kilometre from the
      centres reduced the likelihood of seeing the GP (OR = 0.978, 95% CI = 0.976
      0.979, P < 0.001). Even after controlling for potential confounders a large
      difference remained in how centres responded to calls. CONCLUSIONS: It is not
      certain whether these inequalities in services delivery represent inequity as the
      apposite level or type of response cannot be determined until more is known about
      the appropriateness of the demand for out-of-hours medical care.

PMID- 11510391
TI  - Clinical diagnosis of influenza virus infection: evaluation of diagnostic tools
      in general practice.
AB  - BACKGROUND: With the development of new antiviral agents for influenza, the urge
      for rapid and reliable diagnosis of influenza becomes increasingly important.
      Respiratory virus infections are difficult to distinguish on clinical grounds.
      General practitioners (GPs) however, still depend on their clinical judgement.
      AIM: To evaluate the importance of clinical symptoms in the diagnosis of
      influenza virus infection. DESIGN OF STUDY: A multicentre questionnaire study.
      SETTING: Eighty-one patients from 14 general practices. METHOD: Patients with
      fever and at least one constitutional symptom and one respiratory symptom were
      included. A questionnaire with the medical history and clinical symptoms was
      completed and a combined nose-throat swab was taken. Virus culture, rapid
      culture, and polymerase chain reaction (PCR) amplification were performed on each
      specimen. Multivariate analysis was used to obtain the best predictive model.
      RESULTS: By using PCR, an increase was seen in the detection of the viral
      pathogens compared with the results of culture. In 42 out of 81 patients PCR was
      positive for influenza. A positive predictive value (PPV) of 75% was observed for
      the combination of headache at onset, feverishness at onset, cough, and
      vaccination status during the period of increase influenza activity. Criteria
      used by the ICHPPC-2 resulted in a PPV of 54%. The PPV for diagnosis made by the
      GP was 76%. CONCLUSION: Although influenza is difficult to diagnose on clinical
      grounds, the GPs in this study were able to diagnose influenza as such more
      accurately on their judgement than by the other criteria.

PMID- 11510392
TI  - A quasi-randomised controlled trial of water as a quick softening agent of
      persistent earwax in general practice.
AB  - BACKGROUND: Earwax is a common problem in general practice. The incidence of
      complaints owing to earwax in general practice in the Netherlands is 39.3 per
      1000 patients. AIM: To determine the feasibility of a strategy using water as a
      quick dispersant for persistent earwax, compared with the usual strategy using
      oil as a dispersant for three days in a general practice setting. DESIGN OF
      STUDY: Practice based, prospective controlled intervention study. SETTING: Forty
      two patients (59 ears) in four general practices in the Netherlands. METHOD:
      Patients with persistent earwax were randomised into an intervention group and a
      control group. For patients in the intervention group, water drops at body
      temperature were dropped into the impacted ear and the auditory meatus was
      blocked with a wet wad of cotton. After the patient had waited for 15 minutes in
      the waiting room a series of attempts at syringing was completed. Patients in the
      control group received the usual strategy and were instructed to soften the
      earwax with oil each night before sleeping and to block the auditory meatus with
      a wad of cotton, for three days. They were asked to come back after three days
      for the second attempt of syringing. For both strategies the mean number of
      syringing attempts (and 95% confidence interval) was calculated and compared by
      testing the difference between the means using a t-test for independent samples.
      All ears in which the wax was still persistent after another five syringing
      attempts were given the value of 6 in the calculations. RESULTS: The mean number
      of syringing attempts needed per patient in the intervention group was 3.0 (95%
      CI = 2.4 to 3.6) and for the control group, the mean was 2.4 (95% CI = 1.7 to
      3.1). The difference between means (0.6, 95% CI = 0.3 to 1.5) was not
      statistically significant (P = 0.18). CONCLUSION: A patient with persistent
      earwax can stay in the waiting room following the initial series of five attempts
      at syringing, with water instilled in the ear canal. After 15 minutes, the earwax
      is removed as easily as in the usual strategy using oil instilled for three days.
      The strategy using water as a dispersant for persistent earwax is quick and more
      convenient for the patient.

PMID- 11510393
TI  - The prevalence of asthma and heart disease in transport workers: a practice-based
      study.
AB  - BACKGROUND: There has been widespread concern that the increasing incidence of
      asthma observed during the late 1980s might have arisen because of environmental
      pollution, and in particular vehicle pollution. The General Practice Morbidity
      Survey in 1991/92 (MSGP4) collected data on occupation, employment status, and
      smoking habit linked individually to each patient record. OBJECTIVES: To examine
      whether people with occupations that have high exposure to vehicle exhaust fumes
      have an increased prevalence of asthma, acute respiratory infections, and
      ischaemic heart disease (IHD). METHOD: Men aged 16 to 64 years were grouped by
      Standard Occupational Classification codes; 93,692 employed and 20,858 not
      employed men were studied separately. Those with likely high occupational
      exposure were grouped together ('all-exposed')--the remainder occupations in
      corresponding chapters of the code were used as controls. We compared 12-month
      age and smoking standardised disease prevalence ratios for asthma, chronic
      obstructive pulmonary disease (COPD), acute respiratory infections (IHD), and all
      circulatory disorders in the all exposed and individual exposed occupations with
      their matching controls. Also the mean frequency of consultations per person
      consulting was calculated for each occupational group and disease. RESULTS: For
      employed persons, the prevalence ratio (PR) for asthma in the all-exposed, (116,
      95% confidence interval [95% CI] = 101-130) exceeded that for all employed
      persons (100); however, the difference compared with chapter-matched controls (PR
      = 97, 95% CI = 92-103), was not statistically significant. Results for COPD were
      similar. Prevalence ratios in motor mechanics, a high-exposure group, were 98
      (95% CI = 70-127) 96 (95% CI = 70-123) for asthma and COPD respectively. Among
      the employed, prevalence ratios for IHD in all but one of the individual
      occupation groups examined did not differ from the average, however among those
      not employed the ratio in the all-exposed (PR = 152, 95% CI = 128-174) exceeded
      that in the controls (PR = 112, 95% CI = 104-120). CONCLUSION: Occupational
      groups exposed to motor vehicle pollution have a marginally increased prevalence
      of asthma compared with working males generally, though not compared with
      occupation matched controls. This study has demonstrated a methodology for using
      GP data to examine occupation-related disease. This could be used in future by
      augmenting GP data with occupation and smoking information.

PMID- 11510394
TI  - Practice size: impact on consultation length, workload, and patient assessment of
      care.
AB  - BACKGROUND: Variations in practice list size are known to be associated with
      changes in a number of markers of primary care. Few studies have addressed the
      issue of how single-handed and smaller practices compare with larger group
      practices and what might be the optimal size of a general practice. AIM: To
      examine variations in markers of the nature of the care being provided by
      practices of various size. DESIGN OF STUDY: Practice profile questionnaire
      survey. SETTING: A randomised sample of general practitioners (GPs) and practices
      from two inner-London areas, stratified according to practice size and patients
      attending the practice over a two-week period. METHOD: Average consultation
      length was calculated over 200 consecutive consultations. A patient survey using
      the General Practice Assessment Survey instrument was undertaken in each
      practice. A practice workload survey was carried out over a two-week period.
      These outcome measures were examined in relation to five measures of practice
      size based on total list size and the number of doctors providing care. RESULTS:
      Out of 202 pratices approached, 54 provided analysable datasets. The patient
      survey response rate was 7247/11,000 (66%). Smaller practices had shorter average
      consultation lengths and reduced practice performance scores compared with larger
      practices. The number of patients corrected for the number of doctors providing
      care was an important predictor of consultation length in group practices.
      Responders from smaller practices reported improved accessibility of care and
      receptionist performance, better continuity of care compared with larger
      practices, and no disadvantage in relation to 10 other dimensions of care.
      Practices with smaller numbers of patients per doctor had longer average
      consultation lengths than those with larger numbers of patients per doctor.
      CONCLUSION: Defining the optimal size of practice is a complex decision in which
      the views of doctors, patients, and health service managers may be at variance.
      Some markers of practice performance are related to the total number of patients
      cared for, but the practice size corrected for the number of available doctors
      gives a different perspective on the issue. An oversimplistic approach that fails
      to account for the views of patients as well as health professionals is likely to
      be disadvantageous to service planning.

PMID- 11510395
TI  - Informal carers--the role of general practitioners and district nurses.
AB  - Six million informal carers provide support for aged and disabled people in the
      United Kingdom. Government policies suggest that primary care teams are the main
      support for carers. This postal survey of 300 general practitioners (GPs) and 272
      district nurses (DNs) aimed to determine current practice and views on their role
      in supporting informal carers. In practice, GPs and DNs lack time, resources, and
      training to provide support, and see themselves in a reactive role only.

PMID- 11510396
TI  - Benchmarking using simulated clinical scenarios: a feasibility project.
AB  - 'Benchmarking' clinical practice and integrating such data with national
      guidelines offers a way of establishing standards for use in clinical governance.
      We report on a feasibility project for benchmarking clinical practice in one
      topic area (otitis media) using simulated clinical scenarios. Consistency and
      variations in clinical management were identified for different scenarios.
      Participants perceived the process likely to reflect actual practice and effect
      change in clinical management.

PMID- 11510397
TI  - Reasons for patient removals: results of a survey of 1005 GPs in Northern
      Ireland.
AB  - There has been considerable debate on the issue of general practitioners (GPs)
      removing patients from their lists. The second report of the Health Service
      Ombudsman addressed this area in some detail and, among other observations,
      commented on the lack of information available on this subject. This is a report
      on a questionnaire survey of GPs, aimed at finding out their reasons for removing
      patients and their feelings about the changes that have been proposed regarding
      their automatic right to remove patients without giving them a reason.

PMID- 11510398
TI  - Undiagnosed and untreated wheezing in a cohort of adolescents with a family
      history of allergic disease.
AB  - Wheezing is a common symptom among adolescents. A cross-sectional survey was
      undertaken of a prospective cohort of teenagers with a close family history of
      allergy. The results demonstrate the prevalence of wheezing, the diagnosis of
      asthma, and the treatment of symptoms in this group. The findings suggest that
      undiagnosed and inadequately or untreated wheezing is as common among adolescents
      with a family history of allergic disease as in the general adolescent
      population, and can be associated with severe symptoms.

PMID- 11510399
TI  - A systematic review of vertigo in primary care.
AB  - The symptom of vertigo is usually managed in primary care without further
      referral. This review examines the evidence on which general practitioners can
      base clinical diagnosis and management of this relatively common complaint.
      Research in this area has in the main been from secondary and tertiary centres
      and has been of variable quality. Indications are that the conditions that
      present in general practice are most likely to be benign positional vertigo,
      acute vestibular neuronitis, and Meniere's disease; however, vascular incidents
      and neurological causes, such as multiple sclerosis, must be kept in mind. An
      important practice point is that vestibular sedatives are not recommended on a
      prolonged basis for any type of vertigo. There is a need for basic
      epidemiological and clinical management research of vertigo in general practice.

PMID- 11510400
TI  - Routine care of people with HIV infection and AIDS.

PMID- 11510401
TI  - Prescribing for lower respiratory tract infection.

PMID- 11510402
TI  - TB and prisons.

PMID- 11510403
TI  - Risk information in general practice.

PMID- 11510404
TI  - Topical antibiotics for acute bacterial conjunctivitis.

PMID- 11510405
TI  - Local research ethics committees.

PMID- 11510406
TI  - Carpal tunnel syndrome.

PMID- 11510407
TI  - Role models and the clinical influences.

PMID- 11510408
TI  - Patients' views on anxiety and depression.

PMID- 11510409
TI  - PUNs and PUEs, DENs and SANs.

PMID- 11510410
TI  - Patient consultation satisfaction scores.

PMID- 11510411
TI  - Out-of-hours palliative care advice line.

PMID- 11510413
TI  - The Bathyclarias-Clarias species flock. A new model to understand rapid
      speciation in African great lakes.
AB  - Phylogenetic relationships between seven species of the catfish species flock
      from Lake Malawi (genus Bathyclarias) and other Clariid catfish have been
      investigated using cytochrome b partial sequences. Here we demonstrate that this
      species flock originated from a widespread, generalist species, Clarias
      gariepinus, still occurring in the lake. Bathyclarias species and their ancestor
      C. gariepinus form a simple model that can be used to understand the mechanisms
      of adaptation and rapid speciation in African Great lakes.

PMID- 11510412
TI  - Phosphorylation by PKA of a site unique to B-Raf kinase.
AB  - The Raf kinases serve as central intermediates to relay signals from Ras to ERK.
      Cell-specific effects of these signals on growth, differentiation and survival
      can be observed due to the recruitment of different isoenzymes of the Raf family.
      The in vitro phosphorylation of a site unique to B-Raf (Ser429) has been proposed
      to be responsible for the negative regulation of the isoenzyme by Akt. Using
      phosphopetide mapping and site-directed mutagenesis we showed that Ser429 is
      phosphorylated upon cAMP elevation in PC12 cells and proposed that PKA is a major
      kinase phosphorylating the B-Raf-specific site in vivo.

PMID- 11510414
TI  - [Notes on the biology of the deep-water shrimp Aristeus antillensis in French
      Guiana].
AB  - In order to describe some aspects of the biology of the deep-water shrimp
      Aristeus antillensis (Crustacea, Decapoda, Aristeidae) in French Guiana (Western
      Central Atlantic), a total of 84 bottom trawls were carried out at bottom depths
      ranging from 200 to 900 m on the Guianan slope during four scientific surveys
      conducted from August 1990 through July 1991. A. antillensis is distributed in
      muddy grounds from 456 to 818 m with a peak abundance in the 500-600-m-depth
      stratum where mean catch rates are about 400 g.h-1. In terms of biomass, catches
      obtained in day time and at night are similar. All samples observed show great
      predominance of females. The size frequency distribution indicates the existence
      of three age-classes for females, probably attributed to three annual cohorts.
      The results of a detailed study of morphometric relationships (length-weight
      relationships) are also presented.

PMID- 11510415
TI  - Time measurement in the photoperiodic induction of sexual rest in the terrestrial
      isopod Armadillidium vulgare (Latreille).
AB  - The photoperiodic control of sexual rest in Armadillidium vulgare was
      investigated using various experimental protocols. When reared in conditions of a
      Nanda-Hamner (i.e. resonance) protocol from their first parturial moult to their
      post experimental moult, females showed a weak resonance effect in sexual rest
      incidence. The transfer from a long day cycle to a symmetrical skeleton
      photoperiod--consisting of two equal light pulses per 24 h of continuous darkness
      -revealed the involvement of a circadian oscillatory system in the photoperiodic
      clock of this species. The data, obtained in the whole experiments, suggested
      that both oscillator and hourglass features are involved in the photoperiodic
      response controlling the sexual rest in Armadillidium vulgare. Moreover, when non
      24-h light-dark cycles (with a long photophase) were applied, a mechanism
      responsible of arrest of reproduction also implied a photoperiodic counter which
      accumulated and added up the photoperiodic information within a sensitive period
      during post parturial intermoult.

PMID- 11510416
TI  - [Molecular characterization of Diplozoidae populations on 5 species of
      Cyprinidae: new data on parasite specificity].
AB  - The genus Diplozoon (Platyhelminth) exhibits one of the most striking modes of
      reproduction. Adults reproduce after the permanent fusion of two larval
      hermaphrodites, which play a symmetrical role. The Diplozoidae are also
      exceptional among the Monogenea Polyopisthocotylea for two other reasons. They
      represent the only group really diversified on continental freshwater fishes;
      however, this diversification is difficult to evaluate since few morphoanatomical
      criteria are available to distinguish species and their host specificity is
      atypically variable among the Monogenea. For the first time in the Diplozoidae,
      the problems of species definition and of host specificity are examined using
      molecular tools. Two ribosomal markers (ITS2 and 28S rDNA (D1)) have been
      sequenced in five Diplozoidae, interacting with five Cyprinidae host species: the
      corresponding parasite-host systems have been well characterised, revealing some
      contrasting situations in the relations between Diplozoidae and Cyprinidae. Some
      species are effectively strictly host specific, but Diplozoon scardinii initially
      considered as a specific species on Scardinius erythrophtalmus and D. homoion on
      Rutilus rutilus are proposed to be a single species on the basis of their
      identical ITS2 and 28S rDNA sequences. On the same basis we proposed that D.
      paradoxum is able to parasitize two fish species, Abramis brama and Blicca
      bjoerkna, despite the morphological differences observed between the two
      xenopopulations. Phylogenetic relationships among Diplozoidae species were
      estimated with ITS2 sequences while cytochrome b sequences were used for their
      fish hosts. Finally, the comparison between these two molecular phylogenies seems
      to exhibit the phenomenon of cospeciation.

PMID- 11510417
TI  - Anti-inflammatory properties of molecular hydrogen: investigation on parasite
      induced liver inflammation.
AB  - Molecular hydrogen reacts with the hydroxyl radical, a highly cytotoxic species
      produced in inflamed tissues. It has been suggested therefore to use gaseous
      hydrogen in a new anti-inflammatory strategy. We tested this idea, with the aid
      of the equipment and skills of COMEX SA in Marseille, a group who experiments
      with oxygen-hydrogen breathing mixtures for professional deep-sea diving. The
      model used was schistosomiasis-associated chronic liver inflammation. Infected
      animals stayed 2 weeks in an hyperbaric chamber in a normal atmosphere
      supplemented with 0.7 MPa hydrogen. The treatment had significant protective
      effects towards liver injury, namely decreased fibrosis, improvement of
      hemodynamics, increased NOSII activity, increased antioxidant enzyme activity,
      decreased lipid peroxide levels and decreased circulating TNF-alpha levels. Under
      the same conditions, helium exerted also some protective effects, indicating that
      hydroxyl radical scavenging is not the only protective mechanism. These findings
      indicate that the proposed anti-inflammatory strategy deserves further attention.

PMID- 11510418
TI  - [Original humus forms in a semi-deciduous tropical forest in Guadeloupe].
AB  - Humus profiles underneath the canopy of dominant tree species in two secondary
      semi-evergreen forest sites in Grande-Terre (Guadeloupe) were analysed with a
      micromorphological method. In the vertisol of a tree plantation, the humus formed
      was rather similar under all tree species being an eumull and essentially due to
      the activity of the endoanecic earthworm Polypheretima elongata. In a natural
      secondary forest located on a steep slope and associated with a rendzina soil
      (without endoanecic earthworms), the humus forms were described at lower, mid-
      and upper slope. In this forest, two particular humus forms were observed. At the
      middle slope, underneath the canopy of Pisonia subcordata L. that produces
      nitrogen-rich litter, a calcareous amphimull, characterised by an OH horizon made
      of millipede faecal pellets, was formed. In the upper slope, underneath the
      canopy of Bursera simaruba (L.) Sarg. that produces a litter rich in resins and
      aromatic compounds that are poorly consumed by soil animals, a dysmull with a
      thick root mat (OFRh horizon) developed. Other humus forms were intermediate. The
      formation of these humus forms is discussed.

PMID- 11510419
TI  - [Diet of an anecic earthworm from the Colombian savannas: questioning ecological
      groups].
AB  - An ecological classification based on a set of morphological characters may be
      used to describe earthworm functions in soil. However these relationships have
      been seldom verified. Gizzards of the earthworm Martiodrilus carimaguensis
      (Glossoscolecidae) were studied to find out if its anecic morphology was in
      agreement with its diet (shallow litter remains and deep organo-mineral
      material). By direct observation of 13 adults' gizzard contents with a dissecting
      and a phase contrast microscope, the volumetric percentage of plant fragments,
      roots, amorphous organic matter and mineral particles reached respectively 63, 5,
      6.5 and 30% v/v. Eighty percent of plant fragments were microscopic, and mostly
      incorporated into the organo-mineral earthworm casts well preserved in the
      gizzard. Coprophagy and rhizophagy were the dominant feature of M. carimaguensis
      diet. Yet, the casts produced revealed a high variability in its diet, what could
      be related to transitional adoption of a typical anecic diet during some periods.

PMID- 11510420
TI  - Variations in food intake of Pecten maximus (L.) from the Bay of Brest (France):
      influence of environmental factors and phytoplankton species composition.
AB  - Previous studies carried out in the bay of Brest on daily shell growth of Pecten
      maximus have demonstrated that temperature is a major control on daily shell
      growth in contrast to food supply. However, repeated events of slow growth have
      been observed during diatom and dinoflagellate blooms. The aim of this study was
      to determine how fluctuations in environmental parameters influence P. maximus
      food intake and daily shell growth rate. In 1995, P. maximus food intake and
      growth were highest when Cerataulina pelagica (diatom) blooms occurred and lowest
      during Gymnodinium cf. nagasakiense (dinoflagellate) blooms. During blooms of
      other diatom species, P. maximus food intake and growth were high when the algal
      concentration did not exceed a critical threshold, dependent upon the dominant
      species and sedimentation rate of diatoms. These results demonstrate that the
      morphological and physiological features of phytoplankton bloom species strongly
      affect benthic microphytophagy, a component of benthic-pelagic coupling.

PMID- 11510421
TI  - [Health and the city: physical health and mental health].
AB  - In France, city size has very little bearing on the mortality rate as a function
      of age and life expectancy and it is in large cities that these indicators are
      the most favorable. No increase in maternal or infant mortality rates or deaths
      due to cancers has been observed in large cities. The lower mortality rate linked
      to respiratory and cardiovascular diseases in large urban areas contradicts the
      fears concerning the impact of air pollution. Deaths linked to lifestyle are less
      frequent in big cities, which could be due to social structures (socio
      professional level: the proportion of white-collar workers and professionals is
      higher in bigger cities than in the suburbs or small cities). However, although
      the overall mortality rate is lower, it should be emphasized that there is in
      large cities a greater incidence of sexually transmitted diseases, AIDS and
      certain infectious diseases (because of social diversity and the fact that
      certain individuals seeking anonymity and marginality are drawn to large cities).
      In terms of mental health, the breakdown of family structures, instability,
      unemployment, the lack of parental authority and failing schools render
      adolescents vulnerable and hinder their social integration. When the proportion
      of adolescents at risk is high in a neighborhood, individual problems are
      amplified and social problems result. In order to restore mental and social
      health to these neighborhoods, ambitious strategies are necessary which take into
      account family and social factors as well as environmental ones. At the present
      time, when physical health is constantly improving, the most pressing problems
      are those related to lifestyle and mental health which depend for a large part on
      social factors.

PMID- 11510422
TI  - [The Venezuelan University: Teaching versus scientific production?].

PMID- 11510423
TI  - [Morphological characterization of annatto fruits 9bixa orellana L.) and its
      correspondence with protein and isoenzym patterns].
AB  - A group of 32 annatto genotypes collected in five Venezuelan regions (Oriente,
      Centro, Llanos, Andes and Amazonas) and in Brazil were used for morphological
      studies. The fruit variables with the greatest discriminatory power in the
      formation of groups were capsule size, spinosity and seed size. On the other
      hand, an association group among the variables spinosity, spine length,
      dehiscence and apex shape were formed, also a proportional association between
      capsule and seed size, and between dehiscent capsule and brown coloured seeds.
      Additionally, in order to discriminate morphological variables behaviour in
      respond to electrophoretic variables, a group of protein and isozyme bands
      associated with fruit characteristics were established. Therefore, a
      classification system of this species was possible using morphological studies of
      the capsules, even though a determined association relating morphological and
      molecular patterns was not found.

PMID- 11510424
TI  - [Identification and genetic variability of annatto genotypes (Bixa orellana L.)
      by means of hydrosoluble proteins and isoenzymes].
AB  - In order to identify and to determine the genetic variability of 36 annatto
      genotypes (Bixa orellana L.) collected in five Venezuelan regions (Oriente,
      Centro, Llanos, Andes and Amazonas) and in Brazil, hydrosoluble protein patterns
      as well as specific isozyme patterns (alpha-esterase, beta-esterase and
      peroxidase) were studied using extracts of germinated annatto seeds with radicles
      of 10 to 15 mm long. Each electrophoretic system allowed genotype discrimination
      by means of unique banding patterns: both the hydrosoluble protein and the
      electrophoretic system of beta-esterase with nine banding patterns each; whilst
      alpha-esterase and peroxidase discriminated eight and three genotypes,
      respectively. On the other hand, a combination of all the systems permitted a
      greater discrimination since 34 out of 36 genotypes could be distinguished. Eight
      mayor groups were formed that showed high levels of genetic diversity (40 to 60%)
      with no association between geographic and genetic distances, probably because of
      human influence in the aleatory distribution of this crop. Results obtained
      indicated that using electrophoretic banding patterns, a classification system
      could be established for identification and genetic variability purposes in this
      species.

PMID- 11510425
TI  - [Some attributes of community structure of fishes in Laguna Grande de Obispo,
      Golfo Cariaco, Sucre State, Venezuela].
AB  - Species composition, relative abundance, diversity and community structure of
      fishes were studied from monthly sampling during December 1995 to November 1996
      in the Laguna Grande de Obispo, Gulf of Cariaco, Sucre State, Venezuela. Sampling
      were realised in 3 stations inside the lagoon with a small beach seine and the
      other 4 stations with a large beach seine. Seventy four species belonging to 33
      families and 68 genera were identified of which 8 species dominated, constituting
      90.43% of total catch. Mugil curema, Xenomelaniris brasiliensis, Opistonema
      oglinum, Atherinomorus stipes and Anchoa hepsetus were present in high abundance
      in the biomass. M. curema dominated the catch with large seine while X.
      brasiliensis, M. curema and Eucinostomus argenteus dominated the catch with small
      seine. Species diversity (H') ranged from 2.968-4.607 bits/ind and species
      richness of Margalef from 2.752-7.464. An inverse analysis realized on catches by
      small seine and based on nodal constancy and fidelity allowed to define a pattern
      of spatial distribution of 9 groups containing 1 to 11 species on the basis their
      abundance, frequency of appearance and ecological characteristics of each area.
      An analysis of correlation showed that the salinity, dissolved O2 and
      precipitation did not show any significant correlation with the ecological
      parameters studied but existed significant correlation with average surface water
      temperature (p < 0.05), number of species (S), individuals (N), diversity (H')
      and species richness (D). The positive correlation was found with surface
      temperature but no relationship with relative dominance (D1 and D2). The CPUE in
      biomass did not show any significant association with temperature.

PMID- 11510426
TI  - [A new species of amphipod crustacean of the genus Amphilochus (Crustacea,
      Amphipoda, Amphilochidae) from Venezuela].
AB  - A new species of amphipod Crustacea (Gammaridea, Amphilochidae) of the genus
      Amphilochus Bate, 1862, is described. The species was collected in Phallusia
      nigra (Savigny, 1816) at depths between 0 and 2 m, in the pier piles of the
      Marina El Ancla and Los Manglares gas station in Morrocoy National Park (Falcon
      State, Venezuela), during the months of June and July 1998. The main differences
      between A. ascidicola new species and all others species of the genus recorded
      from the Gulf of Mexico and the Caribbean Sea, are given.

PMID- 11510427
TI  - [Effects of non-depolarizing muscle relaxants on the duration of mivacurium].
AB  - The interaction between Mivacurium and several muscle relaxants results in a slow
      recovery. We have previously described that small doses of d-tubocurarine prolong
      the duration of two successful administrations of Mivacurium. The present
      investigation was designed to uncover if such an effect could be observed after
      other neuro-muscular blocking drugs were administered, and if so, its consistency
      during the different methods of their use. Patients (n = 224) were anesthetized
      with Enflurane and randomly assigned to two control groups which received 100
      micrograms/Kg-1 Mivacurium as a bolus or primed. Other groups received:
      Rocuronium (60 micrograms/Kg-1), Vecuronium (10 micrograms/Kg-1), Atracurium (60
      micrograms/Kg-1), d-tubocurarine (50 micrograms/Kg-1) or Pancuronium (8
      micrograms/Kg-1) before, after or as a mixture with 90 micrograms/Kg-1 of
      Mivacurium. The clinical effect was monitored by electromyography and the results
      show that all these agents prolong the duration of Mivacurium, the last three in
      a statistically significant fashion independently of the mode of administration.
      Current hypothesis are reviewed, but no definitive clues are obtained to explain
      the present results. Our conclusions must be considered as further research on
      the interaction between non-depolarizing muscle relaxants and a base for new
      theories on interactions.

PMID- 11510428
TI  - [Viability and activity of the lactic bacteria (Streptococcus salivarius ssp
      thermophilus y Lactobacillus delbrueckii ssp bulgaricus) del yogurt en
      Venezuela].
AB  - National and international legislations have agreed that the population of lactic
      bacteria in yogurt must be viable and not less than 10(6) ufc/g. In Venezuela,
      during last years, observations indicate that the number of viable cells in some
      commercial samples show high variations, as low levels. This research attempted
      to find the origin of this problem in the local industry. For this purpose 105
      commercial samples were analyzed during their shelf life and 32 samples of yogurt
      prepared in the laboratory following the flow diagram of the local industry. The
      different conditions of freeze dried lactic culture, were also analyzed. These
      samples were evaluated for viable cell count of lactic bacteria and possible
      variations of pH and acidity. The absence or low number of lactic bacteria
      detected in some commercial samples is due to the use of inadequate working
      cultures that show imbalanced proportions of the two microorganisms, besides a
      low count below 106 ufc/g. The succesive propagation and storage time of mother
      culture, and the overacidification of the product, produce subletal injury to the
      microbial cells of the yogurt starter culture. The data indicate that
      manufacturing practices significantly affect the survival of the lactic flora.

PMID- 11510429
TI  - Microbiological quality of the bivalve Pinctada imbricata commercialized in
      Cumana, Venezuela.
AB  - The habitual consumption of oysters in the city of Cumana, Venezuela, is made in
      poor sanitary conditions, therefore a study was carried out to determine the
      sanitary quality of the product. For this, 120 samples of oyster Pinctada
      imbricata were collected directly from: a) Fishing boats (unhandled samples) and
      b) after being shucked by the salesman (handled samples). Unhandled samples
      showed the following MPN/g: Faecal coliforms < 3 - 2.2 x 10, Aeromonas sp. < 3 -
      1.1 x 10(3), Staphylococcus aureus < 3 - 7.5 x 10; Clostridium perfringens < 3 -
      9.3 x 10); cfu/g Enterobacteriaceae 3 - 4.1 x 10(2); total aerobes 2.9 x 10(2) -
      6.9 x 10(5); 6% of S. aureus were coagulase positive. Values of MPN/g of handled
      samples were higher: Faecal coliforms 4 - 4.6 x 10(2); E. coli 9 - 2.1 x 10(2),
      Aeromonas 3 - 4.6 x 10(2), S. aureus 2.3 x 10 - 4.6 x 10(2), C. perfringens < 3 -
      2.8 x 10(2), and cfu/g counts of Enterobacteriaceae 5.4 x 10 - 6.5 x 10(6), total
      aerobes 30 - 2.8 x 10(5); 25% of S. aureus were coagulase positive. Salmonella
      sp. was detected in two of the handled samples. These results suggest
      contamination in growth areas of bivalve and during the collecting operation,
      which is increased by handling of the product by the salesman.

PMID- 11510430
TI  - Functional properties of corn, banana and potato starch blends.
AB  - Potato, corn and banana starches were blended in various combinations and ratios.
      Stability and clarity, freeze-thaw stability, water retention capacity and
      apparent viscosity of the pastes (prepared with a hydrothermic treatment using
      100 degrees C for 30 min) were evaluated. In general, the samples stored at room
      temperature (28 degrees C) presented stability as well as low retrogradation
      rate. However, in the samples stored at 4 degrees C the propagation and
      maturation of crystals in the amylopectin component were favored, increasing
      sample retrogradation. A synergistic effect was shown in some starch blends. The
      blends had poor stability to freeze-thaw cycle, but a high synergestic effect was
      presented in water retention capacity. Potato:banana and corn:potato blends
      showed a synergistic effect in the apparent viscosity and in general, starch
      blends had stability during the 30-min test.

PMID- 11510431
TI  - [Pharmacological biomodulation in cancer].
AB  - The discovery of the P-glycoprotein as a mediator of multidrug resistance (MDR)
      represents one of the most important research accomplishments in antineoplastic
      pharmacology during the last decade. Demonstration of Pgp in epithelial tissues,
      untreated and chemotherapeutically pretreated human malignancies, and
      identification of various agents capable of reversing in vitro resistance has
      generated enthusiasm for clinical studies throughout the world. This review
      discusses recent developments of experimental and clinical investigations of MDR
      reversing agents in cancer.

PMID- 11510432
TI  - [New observations of atrapamoscas tijereto (Tyannus savanna) (aves: tyrannidae)
      in the Colombian caribean coast].

PMID- 11510434
TI  - Diet, monoamine neurotransmitters and appetite control.
AB  - This article has attempted to point out some of the relationships between 5-HT
      and catecholamine (NE, DA) neurons in brain and the control of appetite and food
      intake. At least two bodies of evidence support this connection. The first is
      pharmacologic, and demonstrates that drugs that stimulate transmission across 5
      HT and/or catecholamine synapses suppress hunger and food intake. The second is
      physiologic and metabolic, and reveals that the ingestion of foods, on either an
      acute (single meal) or chronic basis, can reliably modify the uptake of TRP and
      TYR into brain (and hypothalamus), and directly alter the synthesis of their
      transmitters (5-HT and the catecholamines, respectively). The synthesis of these
      two bodies of information has led to models by which (1) changes in dietary
      carbohydrate ingestion, by modifying brain TRP uptake and 5-HT production, may
      cause like changes in 5-HT release, and in the stimulation of 5-HT receptors in
      brain circuits that control carbohydrate appetite, and (2) dietary protein
      intake, by altering brain TYR uptake, directly influences DA and NE synthesis
      (notably in hypothalamus), perhaps providing a signal to brain circuits
      monitoring dietary protein adequacy regarding protein intake. In this case, one
      might imagine that stimulating DA and/or NE receptors in such circuits might
      suppress protein intake, a possibility we are now examining in rats. As indicated
      in the Introduction, the broader issue being touched upon in this article
      concerns the body's need to acquire and maintain an optimal (or adequate)
      nutritional balance (for growth and ultimately, reproductive success). Rats and
      humans evolved in an environment that does not provide continuous access to all
      essential nutrients, and one that presents nutrients in a complex matrix (other
      animals, plants) that can also include toxic compounds. Together with the fact
      that animals and humans do not carry a guidebook to healthy eating, we must
      presume that the brain mechanisms that have evolved to optimize the acquisition
      of essential nutrients are 'automatic' (i.e., not conscious) and quite complex.
      In this context, the relationships described here must be viewed as rudimentary,
      touching only a small portion of this complex regulatory mechanism. The hope is,
      as further insights develop, that we will gain a better understanding of the
      workings of these mechanisms, and also be able to apply this knowledge to the
      development of better pharmacologic (and other) aids for controlling appetite and
      obesity in our modern, man-made environment.

PMID- 11510433
TI  - Undernutrition and mental development.

PMID- 11510435
TI  - Nutrients and affective disorders.

PMID- 11510436
TI  - Nutrition, serotonin and behavior in anorexia and bulimia nervosa.

PMID- 11510437
TI  - Lipids in neural function: modulation of behavior by oral administration of
      endocannabinoids found in foods.

PMID- 11510438
TI  - Nutritional impact on sleep-wake cycle.

PMID- 11510439
TI  - Interaction of iron deficiency anemia and neurofunctions in cognitive
      development.

PMID- 11510440
TI  - Aging, B vitamins and cognitive decline.

PMID- 11510441
TI  - Diet-related prevention of Alzheimer's disease: different hypotheses.

PMID- 11510442
TI  - Nutritional pathogenesis and prevention of stroke.

PMID- 11510443
TI  - Risk from exposure to metals: deficits and excesses (Cu, Fe, Mn, Al, Cr, B).

PMID- 11510444
TI  - Nutritional reversion of cognitive impairment in the elderly.

PMID- 11510445
TI  - Metabolic encephalopathies: liver disease, renal failure, critical illness.

PMID- 11510446
TI  - The ketogenic diet and epilepsy.

PMID- 11510447
TI  - Mechanisms for nutrient effects on brain development and cognition.

PMID- 11510448
TI  - Carbohydrate and fat-based appetite control mechanisms.

PMID- 11510449
TI  - Neuropeptides and the control of energy homeostasis.

PMID- 11510450
TI  - Intrathecal morphine for off-pump coronary artery bypass patients.
AB  - Due to the fact that patients have increased mental alertness following off-pump
      coronary artery bypass (OPCAB), pain management in the immediate postoperative
      period is a major concern. Thirty-two patients underwent OPCAB grafting, 20
      received 5 mcg/kg morphine sulfate intrathecally. This group was compared with 12
      patients who did not receive intrathecal morphine. All patients were verbally
      evaluated for pain using the Wong-Baker Visual Analog Scale at eight, 12 and 24
      hours. All the scores were highly statistically significant in favor of the
      intrathecal group. No significant complications were seen in this group of
      patients. It is concluded that intrathecal morphine at 5 mcg/kg is effective and
      safe in maintaining comfort for OPCAB patients in the immediate postoperative
      period.

PMID- 11510451
TI  - [Progress in electronic informatics application in dentistry].

PMID- 11510452
TI  - Doc Holliday, DDS: 150th anniversary.

PMID- 11510453
TI  - Neuromuscular disorders: gene location.

PMID- 11510454
TI  - Mitochondrial encephalomyopathies: gene mutation.

PMID- 11510455
TI  - [Pneumatosis intestinalis secondary to acute mesenteric ischemia].

PMID- 11510456
TI  - [Dysphagia].

PMID- 11510457
TI  - Role of MR imaging in the evaluation of low back pain (orthopedic surgeon's
      view).
AB  - In this article, the role of magnetic resonance imaging in the evaluation of
      degenerative lumbar disorders causing low back pain and radicular symptoms is
      discussed from an orthopedic surgeon's point of view. Magnetic resonance imaging
      can represent not only morphological, but pathological changes of
      osteoligamentous and neural components of the lumbar spine.

PMID- 11510458
TI  - Kinematic MR imaging of the knee.
AB  - This is an overview of the "cine magnetic resonance (MR) imaging" system and
      rapid (ultra-fast) MR imaging of the knee for evaluation of injury of the
      cruciate ligament including its function during flexion and extension. Cine MR
      imaging using a gating system and a cine acquisition delineates alterations of
      the signal and shape of the cruciate ligaments and menisci. Rapid (ultra-fast) MR
      images with a single acquisition time of half second or less using a mobile knee
      brace and a flexible surface coil has enabled rapid acquisition of moving knee
      motion in multi-image frames. Visualization of the moving normal and torn
      anterior cruciate ligaments indicates that kinematic MR imaging of the moving
      knee is advantageous in evaluating the continuity and tension in the cruciate
      ligaments.

PMID- 11510459
TI  - Sexually transmitted disease clinical preventive services for HIV-infected
      patients.

PMID- 11510460
TI  - [Chronic hepatitis. 3. An actual case].

PMID- 11510461
TI  - [The "relative clause" in private health insurance. The decision of the Federal
      Court on February 21, 2001].

PMID- 11510462
TI  - Balloon replacement of fetal membranes to facilitate emergency cervical cerclage.
AB  - BACKGROUND: Emergency cerclage can be used in cases of cervical incompetence,
      even when fetal membranes bulge through the dilated cervix. To facilitate the
      procedure we used a balloon device to replace the fetal membranes. TECHNIQUE:
      With the patient in a steep Trendelenburg position, after epidural anesthesia,
      the fetal membranes were replaced into the uterine cavity with an inflated
      balloon of the type used for endoscopic preperitoneal dissection. Cervical
      cerclage was done by the McDonald technique. EXPERIENCE: We have done 25
      emergency cerclages with this technique. The following maternal and perinatal
      outcomes were assessed retrospectively: age, medical history, gestational age at
      inclusion and delivery, cervical dilatation at admission, preterm rupture of
      membranes, clinical or histologic chorioamnionitis, birth weight, admission to
      the neonatal intensive care unit, neonatal death, and postnatal course.
      CONCLUSION: Replacing prolapsed fetal membranes with an inflated balloon is a
      convenient technique that allows gestation to be prolonged for an average of 31
      days. Cerclage was feasible when the cervix was widely dilated (more than 4 cm);
      it was associated with prolongation of gestation by a median of 9 days.

PMID- 11510463
TI  - New tool for presenting risk in obstetrics and gynecology.
AB  - BACKGROUND: The Paling Perspective Scale, a means of communicating risk in
      various settings, has been applied to diverse fields such as nuclear power, blood
      banking, and ophthalmology. TECHNIQUE: Statistics of risk for various events in
      obstetrics and gynecology were collected from the literature and directly applied
      to the risk scale. EXPERIENCE: The graphic simplicity and versatility of this
      scale make it adaptable for communicating risks to people of different technical
      and educational backgrounds. CONCLUSION: The Paling Perspective Scale might help
      obstetrician-gynecologists obtain informed consent for surgery, genetic
      counseling, and other topics.

PMID- 11510464
TI  - Plasma adenosine levels and P-selectin expression on platelets in preeclampsia.

PMID- 11510465
TI  - A child with Coxsackie A3 encephalitis.

PMID- 11510466
TI  - Signet cell gastric carcinoma presenting as multiple large skin nodules.

PMID- 11510467
TI  - Plantar warts of defined aetiology in adults and unresponsiveness to low dose
      cimetidine.

PMID- 11510468
TI  - Plasma endothelin-1 levels before and after vascular occlusive test in patients
      with Behcet's disease.

PMID- 11510470
TI  - Misleading information about ALIP and VEGF in myelodysplasia.

PMID- 11510469
TI  - The t(4;14)(p16.3;q32) is strongly associated with chromosome 13 abnormalities in
      both multiple myeloma and monoclonal gammopathy of undetermined significance.

PMID- 11510471
TI  - Pseudo Pelger-Huet anomaly in myelodysplastic syndrome: hyposegmented apoptotic
      neutrophil?

PMID- 11510472
TI  - Alternate designs for conduct and analysis of phase I cancer trials.

PMID- 11510473
TI  - Exogenous platelet-activating factor stimulates cell proliferation in mouse pre
      implantation embryos prior to the fourth cell cycle and shows isoform-specific
      stimulatory effects.
AB  - Mouse embryos secrete molecules homologous to platelet-activating factor (PAF),
      termed embryo-derived PAF (EPAF), which act in an autocrine/paracrine fashion to
      stimulate embryonic development in vitro. Mouse EPAF is thought to consist
      predominantly of hexadecyl (C16) and octadecyl (C18) PAF-like components. Mouse
      pre-implantation embryos cultured with exogenous PAF from the early cleavage
      stages exhibit increased blastocyst cell numbers and rates of mitosis around the
      8-cell stage. We investigated whether exogenous PAF could specifically stimulate
      embryonic cell proliferation prior to the blastocyst stage in the mouse and also
      compared the biological activities of the C16 and C18 PAF isoforms as follows.
      Embryos were cultured for either 24 h or 120 h from the 2-cell stage and their
      total cell numbers were determined or their development assessed in terms of
      their incidence of successful zona-hatching respectively. In each case, embryos
      were cultured in unsupplemented medium or in medium supplemented with either C16
      or C18 PAF (0.5 microM). Compared with controls, culture with C16 PAF produced a
      significant stimulation of mean total per number per embryo and a significant
      increase in the incidence of successful zona-hatching, whilst culture with C18
      PAF had no significant effect. We then cultured 1-cell zygotes for 48 h in
      unsupplemented medium or medium supplemented with either an equimolar mixture of
      C16 and C18 PF or with either C16 or C18 PF alone (each at 0.2 microM). Embryos
      were also scored for cell number at 4 h and 30 h of culture. Although no
      significant effect on mean cell number per embryo was seen following 4 h or 30 h
      of culture with a mixed C16/C18 PAF preparation, culture for 48 h with a mixed
      C16/C18 PAF preparation or with C16 PAF alone produced a significant increase in
      mean cell number per embryo compared with controls - an effect that is likely to
      be receptor-mediated, since culture with an equivalent concentration of C18 PAF
      had no significant effect compared with controls. We have demonstrated that mouse
      zygotes/embryos can respond in a specific manner to exogenous hexadecyl PAF in
      terms of increased rates of cell proliferation prior to cavitation, and must be
      capable of doing so at some time between the first and third, and also between
      the second and fourth, cell cycles. Such embryos presumably express one or more
      classes of functional PAF-receptor molecule during this period (i.e. as early as
      during the 1-, 2- or 4-cell stages). We have also demonstrated that embryonic
      response to exogenous PAF is significantly isoform-specific, which may reflect
      differences between the two isoforms either in affinity for binding to putative
      embryonic PAF-receptor molecules or in their ability to elicit a stimulatory
      response following binding. This observation calls into question the use of
      preparations containing a mixture of hexadecyl and octadecyl PAF isoforms,
      particularly in dose-response studies, in the mouse.

PMID- 11510474
TI  - Determination of urinary pyrraline by solid-phase extraction and high performance
      liquid chromatography.
AB  - Pyrraline is one of the advanced glycation end products formed under non
      enzymatic and non-oxidative conditions in vivo. In this study, we developed a
      novel method for determination of urinary pyrraline using solid-phase extraction
      as a pretreatment procedure prior to determination by high performance liquid
      chromatography (HPLC). The Oasis HLB solid-phase extraction cartridge was used
      for pretreatment of urine samples without hydrolysis. The chromatogram obtained
      clearly revealed the peak for urinary pyrraline owing to prior removal of
      interfering substances in urine samples. The recovery rate of pyrraline was
      97.2+/-3.3% (n=6). The mean excretion level of urinary pyrraline in healthy
      control (20-77 years old, n = 30) was 1.42+/-0.65 micromol/mmol creatinine, and
      the daily variation in the excretion level was considered to be insignificant. We
      propose the above procedure as a simple, rapid, and accurate method for
      determination of pyrraline levels in urine.

PMID- 11510475
TI  - Development of an enzyme immunoassay for serum 16-dehydropregnenolone.
AB  - We have developed an enzyme immunoassay (EIA) for serum 16-dehydropregnenolone
      (3beta-hydroxy-5,16-pregnadien-20-one; 16-DHP). The antiserum against 16-DHP-3
      hemisuccinate conjugated bovine serum albumin (16-DHP-3HS-BSA) was raised in
      rabbits. For use as an enzyme labeled antigen, 16-DHP-3HS was conjugated to
      alkaline phosphatase. The minimal amount of 16-DHP detected was 4 pg (0.013
      pmol)/assay and the measurable range was from 0.06-60 ng/ml (0.191-191 nmol/l).
      The intra-assay coefficient of variation (C.V.) was 4.1% (0.73+/-0.03 ng/ml,
      mean+/-S.D., n=6), and inter-assay C.V. was 7.7% (0.13+/-0.01 ng/ml, n=6). A
      liner relation was observed between the serum sample dilution and the 16-DHP
      concentration. For the recovery study, authentic 16-DHP was added to a serum
      sample (original concentration: 0.10-0.14 ng/ml), and the recovery was found to
      be 94.4-96.8% (final 16-DHP concentrations calculated: 0.29-16.3 ng/ml). To
      investigate the reliability of the present EIA, the values from our EIA were
      compared with those obtained by GC-MS. The 16-DHP concentration could not be
      measured in serum by GC-MS because of its sensitivity. Therefore, the conjugated
      steroid, 16-DHPS, was first enzymatically hydrolysed and then the 16-DHP measured
      by both methods. There was a good correlation between the levels determined by
      these methods (Pearson's correlation coefficient: r=0.927, p<0.001, y=0.74x+3.61,
      n=27). The serum concentrations of 16-DHP in neonates and umbilical vein were
      0.53+/-0.09 ng/ml and 0.88+/-0.61 ng/ml, respectively. No 16-DHP was detected in
      serum from normal healthy adults using the present EIA. These results suggest
      that 16-DHP originates from the fetus and neonate.

PMID- 11510476
TI  - Molecular authentication of Panax ginseng species by RAPD analysis and PCR-RFLP.
AB  - In order to develop convenient and reproducible methods for the identification of
      ginseng drugs at a DNA level, randomly amplified polymorphic DNA (RAPD) and PCR
      restriction fragment length polymorphism (PCR-RFLP) analyses were applied within
      Panax species. To authenticate Panax ginseng among ginseng populations, RAPD
      analysis was carried out using a 20 mer-random primer. The similarity
      coefficients among the DNA of ginseng plants analyzed were low, ranging from
      0.197 to 0.491. In addition, by using PCR-RFLP analysis, very different
      fingerprints were obtained within Korean ginseng plants. These results suggest
      that these methods are able to authenticate the concerned Panax species. Broader
      application of this approach to authenticate other morphologically similar
      medicinal materials is rationalized.

PMID- 11510477
TI  - Apoptosis and mitochondrial damage in INS-1 cells treated with alloxan.
AB  - To evaluate the participation of mitochondrial damage, oxygen radicals and cell
      death in diabetes mellitus, we designed a way to investigate INS-1 cells, rat
      pancreatic beta-cell line, to die by treatment with alloxan which generate
      reactive oxygen species (ROS). Incubation of INS-1 cells with alloxan for 24 h
      resulted in a decrease in viability of cells as well as inhibition of glucose
      stimulated insulin release; this could be prevented by antioxidants, vitamin E
      and butylated hydroxyanisol (BHA). The formation of a DNA ladder and the
      distribution of phosphatidylserine at the external surface of plasma membrane
      were observed as indicators of apoptosis in the cells treated with alloxan at
      concentrations below 0.5 mM. The formation of DNA ladder was prevented by vitamin
      E, BHA and catalase, suggesting that the ROS is involved in the process of
      apoptosis in INS-1 cells treated with alloxan. Lower levels of intracellular ATP,
      collapse of mitochondrial membrane potential and release of cytochrome c from
      mitochondria were also observed in INS-1 cells treated with alloxan, suggesting
      that alloxan caused the damage of mitochondria in cells and was related to the
      process of apoptosis. In contrast, rat liver RLC-18 cells treated with alloxan
      were not observed in the decrease of viability. It follows from the present study
      that mitochondrial damages by ROS generated from alloxan is linked to apoptosis
      in INS-1 cells.

PMID- 11510478
TI  - Modulation of gene expression by (-)-epigallocatechin gallate in PC-9 cells using
      a cDNA expression array.
AB  - Green tea is the most effective cancer preventive beverage. In the light of this,
      the mechanisms of action of tea polyphenols were investigated on the molecular
      levels. We present here the effects of (-)-epigallocatechin gallate (EGCG) on
      expression of 588 genes in human lung cancer cell line PC-9 cells, using a human
      cancer cDNA expression array. The levels of gene expression in non-treated
      control cells, and cells treated with EGCG alone, with the tumor promoter okadaic
      acid alone, and with EGCG plus okadaic acid, were studied, and their expression
      levels were classified into down-regulation (under 0.5 fold) and up-regulation
      (over 2.0 fold) by comparing with the levels of control. Non-treated PC-9 cells
      expressed 163 genes out of 588, and EGCG-treated cells induced down-regulated
      expression of 12 genes and up-regulated expression of 4 other genes. From a
      comparison of gene expression in the cells treated with EGCG and in cells treated
      with EGCG plus okadaic acid, we found the following genes commonly affected by
      EGCG: down-regulation of four genes, NF-kappaB inducing kinase (NIK), death
      associated protein kinase 1 (DAPK 1), rhoB and tyrosine-protein kinase (SKY); up
      regulation of one gene, retinoic acid receptor alpha1. Among them, we think down
      regulation of NIK gene expression is significant for cancer prevention, based on
      evidence that inhibition of NF-kappaB activation is a result of inhibition of
      NIK/IKK signalling complex.

PMID- 11510479
TI  - Geranylgeranylacetone protects guinea pig gastric mucosal cells from gastric
      stressor-induced necrosis by induction of heat-shock proteins.
AB  - Gastric mucosal cell death due to various gastric stressors can cause several
      types of gastric diseases, such as gastric ulcers. In this study, we examined
      cell death following the short-term treatment of guinea pig gastric mucosal cells
      in primary culture with various gastric stressors. The short-term treatment of
      cells with ethanol, hydrogen peroxide or hydrochloric acid caused, in a dose
      dependent manner, cell death in the absence of apoptotic DNA fragmentation and
      chromatin condensation. Cells lost membrane integrity following the treatment
      with each of these gastric stressors, suggesting that necrosis was induced in
      gastric mucosal cells by short-term treatment of the cells with gastric
      stressors. Geranylgeranylacetone, an anti-ulcer drug with heat-shock protein
      inducing properties, protected gastric mucosal cells from the necrotic cell death
      caused by each of these gastric stressors. Pretreatment of cells with low
      concentrations of ethanol (3%), which also induced heat-shock protein, made cells
      resistant to the necrotic cell death caused by the gastric stressors. These
      results suggest that heat-shock proteins is involved in the cytoprotective effect
      of geranylgeranylacetone against necrotic cell death.

PMID- 11510480
TI  - Hepatic injury-specific conversion of mouse plasma hyaluronan binding protein to
      the active hetero-dimer form.
AB  - Plasma hyaluronan binding protein (PHBP) is produced only in liver and kidney in
      mouse. The induction of PHBP mRNA and the conversion of pro PHBP to the active
      hetero-dimer form were studied after CCl4, D-galactosamine, HgCl2 or turpentine
      administration and after partial hepatectomy. The results indicated that the
      administrations of CCl4 and D-galactosamine, which caused hepatic failure, and
      the partial hepatectomy enhanced the conversion of pro PHBP to the active two
      chain form in the plasma. On the other hand, HgCl2 which injured kidney and
      turpentine which led to inflammation were not involved in the activation of PHBP.
      The weak induction and suppression of PHBP mRNA were observed in the liver at 3 h
      and 12 h, respectively, after the CCl4 administration. However, HgCl2 and
      turpentine did not influence the amount of PHBP mRNA. These results suggested the
      hepatic injury-specific activation of PHBP in plasma. PHBP may act as an early
      factor in the cascade for the tissue remodeling in liver following hepatic
      injury, i.e., PHBP activates urokinase, urokinase activates matrix
      metalloproteinases (MMPs) and MMPs degrade extracellular matrix for liver
      regeneration.

PMID- 11510481
TI  - Histopathological study of kidney abnormalities in an experimental SIADH rat
      model and its application to the evaluation of the pharmacologic profile of VP
      343, a selective vasopressin V2 receptor antagonist.
AB  - The aim of this work was to investigate histopathologically the relationship
      between the syndrome of inappropriate secretion of antidiuretic hormone (SIADH)
      and kidney abnormalities and the therapeutic efficacy of VP-343 ((N-[4-[[(2S,3aR)
      2-hydroxy-2,3,3a,4-tetrahydropyrrolo[1,2-alqunoxalin-5(1H)-yl]phenyl]-4'
      methyl[1,1'-biphenyl]-2-carboxamide], a selective vasopressin V2 receptor
      antagonist, in an experimental SIADH rat model. In the model, which was prepared
      by continuously administering 1-desamino-8-D-arginine vasopressin (DDAVP),
      histopathologic abnormalities, such as dilatation of tubules, basophilic changes
      in tubules, inflammatory cell infiltration, and mineralization were found in the
      kidney, accompanied by significant increases in the relative weight of the
      kidney, lung, liver, adrenal gland, and heart. VP-343 was shown to be effective
      in protecting the kidney from the histopathologic abnormalities and to normalize
      the relative weight of the kidney and several common pathophysiologic features,
      such as hyponatremia, hyposmolarity of plasma, hyperosmolarity of urea, and
      oligurea, as described previously. These results demonstrate the occurrence of
      histopathologic abnormalities in the kidney and the efficacy of VP-343 in
      improving abnormalities in the DDAVP-induced SIADH rat model.

PMID- 11510482
TI  - Characterization of specific [3H]nociceptin binding in rat brain and spinal cord.
AB  - The present study was undertaken to characterize simultaneously [3H]nociceptin
      binding to opioid receptor-like 1 (ORL1) receptors in the rat brain and spinal
      cord. Specific binding of [3H]nociceptin to crude membranes from the rat brain
      and spinal cord at 25 degrees C was saturable, reversible and of high affinity,
      and it also exhibited a pharmacological specificity involving the ORL1 receptor.
      The Kd and Bmax values for [3H]nociceptin in the spinal cord were significantly
      lower than those in the brain. At 4 degrees C, there was a significant increase
      in the dissociation constant (Kd) for [3H]nociceptin in the brain and spinal cord
      with little change in the maximal number of binding sites (Bmax) compared with
      that at 25 degrees C. Nociceptin and its analogue, [Phe1 psi(CH2-NH)
      Gly2]nociceptin(1-13)NH2 were found to be potent inhibitors of [3H]nociceptin
      binding to crude membranes from the brain and spinal cord, while opioid ligands
      such as naloxone-benzoylhydrazone, naltrindole and nor-binaltorphimine, exhibited
      an inhibitory effect only at high concentrations. The Ki values for nociceptin,
      its analogue and opioid ligands in the spinal cord were significantly lower than
      those in the brain. There were regional variations in the specific [3H]nociceptin
      binding to crude membranes from the rat brain: a relatively high density of
      [3H]nociceptin binding in the cerebral cortex, hippocampus, thalamus and
      midbrain, moderately dense binding in the corpus striatum and pons/medulla
      oblongata, and the lowest density of binding in the cerebellum. In conclusion,
      the present study has shown that [3H]nociceptin binds selectively to ORL1
      receptors in the rat brain and spinal cord.

PMID- 11510483
TI  - Inhibitory effect of glycyrrhizin on the phosphorylation and DNA-binding
      abilities of high mobility group proteins 1 and 2 in vitro.
AB  - The physiological correlation between glycyrrhizin (GL) and high mobility group
      proteins I and 2 (HMG1/2) and the inhibitory effect of GL on their
      phosphorylation by three protein kinases (CK-I, CK-II and PKC) were investigated
      biochemically in vitro. It was found that GL binds directly to HMG1/2, because
      (i) HMG1/2 have a high affinity with a GL-affinity column; and (ii) GL induces
      the conformational changes in HMG1/2. Both purified HMG1/2 functioned as
      phosphate acceptors for these two protein kinases (CK-I and PKC), but not
      phosphorylated by CK-II. Phosphorylation of HMG1/2 by two protein kinases (CK-I
      and PKC) was completely inhibited by a glycyrrhetinic acid derivative (oGA) at
      one-tenth the concentration of GL. Also, the DNA-binding abilities of HNG1/2 were
      reduced by GL in a dose-dependent manner. These results show that the binding of
      GL to HMG1/2 results in the inhibition of their physiological activities (DNA
      binding ability and phosphorylation by PKC or CK-I) in vitro. The GL-induced
      inhibition of the physiological activities of HMG1/2 may be involved in the anti
      inflammatory effect of GL in vivo.

PMID- 11510484
TI  - Cloning and characterization of a cDNA encoding beta-amyrin synthase involved in
      glycyrrhizin and soyasaponin biosyntheses in licorice.
AB  - An oxidosqualene cyclase cDNA, termed GgbAS1, was isolated from cultured cells of
      licorice (Glycyrrhiza glabra) by heterologous hybridization with cDNA of
      Arabidopsis thaliana LUP1 lupeol synthase. The yeast transformed with an
      expression vector containing the open reading frame of GgbAS1 produced beta
      amyrin, indicating that GgbAS1 encodes beta-amyrin synthase involved in the
      glycyrrhizin and soyasaponin biosyntheses in licorice. Northern blot analysis
      showed that the level of beta-amyrin synthase mRNA was drastically changed in the
      cultured licorice cells, whereas the mRNA level of cycloartenol synthase was
      relatively constant.

PMID- 11510485
TI  - Inhibitory effects of evodiamine on in vitro invasion and experimental lung
      metastasis of murine colon cancer cells.
AB  - We have previously reported that evodiamine had a marked inhibitory activity on
      tumor cell migration in vitro. To extend our study, the effects of evodiamine on
      invasion, growth, and metastatic development of colon 26-L5 cells were examined
      here. Evodiamine inhibited the invasion of tumor cells into Matrigel in a
      concentration-dependent manner, and achieved 70% inhibition at 10 microg/ml.
      Treatment of tumor cells with evodiamine for 24 h showed little effect on tumor
      growth at concentrations of less than 10 microg/ml, whereas an over 48-h
      treatment resulted in a concentration- and time-dependent inhibition.
      Pretreatment of tumor cells with 10 microg/ml evodiamine before inoculation into
      mice caused 70% reduction in their lung metastasis formation. When evodiamine at
      10 mg/kg was administered into mice from the 6th day after tumor inoculation, the
      number of tumor nodules in lungs was decreased by 48% as compared to control. The
      inhibition rate was equivalent to that produced by cisplatin, a potent anti
      cancer drug. Evodiamine did not affect the body weight of mice in the
      experimental period, whereas cisplatin caused serious weight loss. These results
      suggest that evodiamine may be regarded as a promising agent in tumor metastasis
      therapy.

PMID- 11510486
TI  - Neuroprotective and neurotrophic effects of quinic acids from Aster scaber in
      PC12 cells.
AB  - Aster scaber T. (Asteraceae) has been used to treat bruises, snakebite, headache,
      and dizziness in traditional Chinese medicine. In the present study, the
      neuroprotective effect of four quinic acid derivatives from A. scaber on amyloid
      Abeta-induced PC12 cell toxicity was investigated. When cells were treated with
      quinic acid derivatives prior to Abeta, cell toxicity was significantly
      diminished. Among quinic acid derivatives, (-)4,5-dicaffeoyl quinic acid (1) gave
      the highest protection against Abeta-induced cell toxicity. In addition, the
      neurotrophic effects of compounds were evaluated by microscopically monitoring
      their potency to induce neurite outgrowth in PC12 cells. Four quinic acid
      derivatives from A. scaber promoted neurite outgrowth in PC12 cells.
      Interestingly, a novel quinic acid, (-)3,5-dicaffeoyl-muco-quinic acid (2) was
      more effective than the other compounds in promoting neurite outgrowth. Unlike
      nerve growth factor, the withdrawal of quinic acids did not result in any
      significant decrease in cell viability. The results suggest that quinic acid
      derivatives from A. scaber might potentially be used as a therapeutic agent in
      Alzheimer disease.

PMID- 11510487
TI  - Effect of dexamethasone palmitate-low density lipoprotein complex on cholesterol
      ester accumulation in aorta of atherogenic model mice.
AB  - In order to confirm the efficacy of dexamethasone palmitate (DP)-low density
      lipoprotein (LDL) complex on experimental atherosclerosis in vivo, we examined
      whether DP-LDL complex could be effective for cholesterol ester accumulation in
      the aorta of atherogenic mice. Nonatherogenic and atherogenic mice were fed with
      normal and atherogenic diet for 14 weeks, respectively. Dexamethasone (DEX),
      lipid emulsion containing DP (DP-LE), or DP-LDL complex was intravenously
      injected once a week from 8 to 14 weeks. Cholesterol levels in serum and aorta in
      the atherogenic mice were significantly higher than those of nonatherogenic mice.
      Injection of DP-LDL complex significantly reduced cholesterol ester (CE)
      accumulation in the aorta of atherogenic mice. The reduction of CE accumulation
      in aorta treated with DP-LDL complexes was 10 and 100 times more potent than that
      with DP-LE and DEX, respectively. The radioactivity in the aorta of atherogenic
      mice treated with 3H-DP-LDL complex was significantly higher than that with 3H-DP
      LE and 3H-DEX at 24 h after injection. Even 7 d after injection, a significant
      amount of radioactivity was present only in the aorta of atherogenic mice treated
      with DP-LDL complex. This result suggests that DP-LDL complex is selectively
      delivered to the atherogenic lesions in the aorta of atherogenic mice, and then
      DP released from the complex inhibits CE accumulation in the aortic intima.
      Therefore, DP-LDL complex may be a good drug-carrier in drug delivery system for
      atherosclerosis.

PMID- 11510488
TI  - Transport characteristics of ebastine and its metabolites across human intestinal
      epithelial Caco-2 cell monolayers.
AB  - The transport characteristics of a selective peripheral H1 receptor antagonist,
      ebastine, a substrate for cytochrome P450 3A4, and its three major metabolites,
      i.e., the hydroxy metabolite of ebastine (M-OH), the pharmacologically active
      metabolite carebastine (Car), and the desbutyrophenone metabolite (des-BP), were
      studied in cultured human intestinal Caco-2 cells expressing a drug efflux pump,
      P-glycoprotein (P-gp), on the apical membrane. The polarized transport of
      [3H]cyclosporin A (CyA), mediated by P-gp in the basolateral to apical direction
      across the Caco-2 cell monolayers, was affected by the presence of ebastine in a
      concentration-dependent manner and significant inhibition was observed at high
      concentrations (>50 microM). M-OH (300 microM) also significantly inhibited
      whereas Car and des-BP did not. Although no marked polarized transport of
      [14C]ebastine in a secretory direction was observed in the Caco-2 systems, the
      flux in the basolateral to apical direction was slightly higher than that in the
      opposite direction at concentrations less than 30 microm. [14C]Ebastine (2
      microM) uptake from the apical side was significantly increased in the presence
      of an excess of cold CyA, suggesting that the efflux process mediated by P-gp may
      be involved in the ebastine uptake by Caco-2 cells. Collectively, these results
      indicate that ebastine (and presumably M-OH) is transported via P-gp in Caco-2
      cells, however, the affinity for P-gp is very low. It is unlikely that the
      secretory transport of ebastine mediated by P-gp will dramatically affect overall
      intestinal absorption in vivo because efficient passive diffusion of this drug
      should occur due to its high lipophilicity. However, it may be advantageous for
      its efficient first-pass metabolism.

PMID- 11510489
TI  - Molecular and pharmacokinetic properties of 222 commercially available oral drugs
      in humans.
AB  - This study was performed to determine the exclusion criteria that differentiate
      poorly absorbed drugs from good drug candidates, and to accelerate drug
      development by exclusion of unnecessary assessment. The molecular and
      pharmacokinetic properties of 222 commercially available oral drugs were
      tabulated and their correlations were analyzed. The exclusion criteria obtained
      were 1) a molecular weight of more than 500, and 2) a ClogP value of more than 5.
      Exceptions to molecular weight criteria were compounds with a sugar moiety, high
      atomic weight, and large cyclic structure. It was also suggested that being a
      substrate for MDRI (P-glycoprotein) does not always result in poor
      bioavailability, and that drug development by chemical modification of a seed or
      lead compound with quantitative structure activity relationship analysis can
      result in lower bioavailability, higher bound fraction and lower urinary
      excretion, which would hamper later development processes and might result in
      considerable drug-drug interaction. The criteria should be adjusted according to
      the pharmacological profiles of the agents in question and depending on the
      estimated profit, but ignoring these criteria may result in a significant waste
      of time and money during drug development.

PMID- 11510490
TI  - Purification and biological activity of acidic polysaccharide from leaves of
      Thymus vulgaris L.
AB  - Polysaccharides are involved in biological responses and can activate complement
      system, which plays an important role in primary host defense mechanisms. We
      investigated anticomplementary activities from spice plants and selected thyme
      (Thymus vulgaris L.) as a potent complementary activator. Acidic polysaccharide
      (TV-3-IIIA-IIa) purified from the hot-water extract of thyme leaves by DEAE
      Toyopearl 650C, Butyl-Toyopearl 650M and Sepharose CL-6B column chromatography
      and preparative HPLC. The purified polysaccharide, TV-3-IIIA-IIa showed potent
      anticomplementary activity via classical and alternative pathway with the
      increase proportional to dosage. TV-3-IIIA-IIa seemed to be a homogenous polymer
      from the results of HPLC and its molecular mass was estimated as 180 kDa. TV-3
      IIIA-IIa mainly consisted of galacturonic acid (44.8 mol%), glucuronic acid (16.7
      mol%), arabinose (11.1 mol%), rhamnose (9.2 mol%), galactose (8.9 mol%) and small
      amounts of glucose, xylose, mannose and fucose. By methylation analysis and
      reactivity to beta-glucosyl Yariv reagent, TV-3-IIIA-IIa was assumed to contain
      small amounts of type II arabinogalactan and large amounts of pectin-like
      polysaccharides in the structure. Based upon these results, TV-3-IIIA-IIa was
      suggested to be a complement activator.

PMID- 11510491
TI  - Identification of 16alpha,19-dihydroxyandrostenedione in the serum of pregnant
      women by gas chromatography-mass spectrometry.
AB  - 16alpha,19-Dihydroxyandrostenedione [16alpha,19-(OH)2 AD], a potential precursor
      of estriol, was identified in the serum of pregnant women by gas chromatography
      mass spectrometry (GC-MS). Preliminary study indicated that the average serum
      concentration of 16alpha,19-(OH)2 AD in 10 normal pregnant women was 154.2+/-20
      pg/ml. In contrast, the serum concentration of 16alpha,19
      dihydroxydehydroepiandrosterone was less than the detection limit (30 pg/mI) of
      the GC-MS method.

PMID- 11510492
TI  - Sustained hyperglycemia and insulin resistance induced by dietary restriction.
AB  - This investigation considered whether defects in insulin secretion and insulin
      action may result in the development of sustained hyperglycemia induced by
      refeeding standard chow pellets. Hyperglycemia, sustained for 36 h was induced,
      in mice that ate standard chow pellets ad libitum after 48 h fasting, but not 24
      h fasting. In 48 h-fasted mice, serum insulin levels were remarkably low and the
      ability of insulin secretion to respond to glucose was decreased, although
      insulin-stimulated glucose disposal was not impaired. However, hyperinsulinemia
      was observed after refeeding for 12 h. The 12 h-refed mice had impaired glucose
      tolerance and were remarkably insulin resistant. These results suggest that
      hyperglycemia induced by the fasting-refeeding was caused by hyperphagia and the
      failure of insulin secretion, and maintained the resulting induced insulin
      resistance.

PMID- 11510493
TI  - Apparent low frequency of sequence variability within the proximal promoter
      region of the cytochrome P450 (CYP) 3A5 gene in established cell lines from
      Japanese individuals.
AB  - The members of the cytochrome P450 (CYP) 3A subfamily play an important role in
      the metabolism of more than 50% of the drugs metabolized by CYPs. Among the CYP3A
      members, CYP3A5 is known to exhibit polymorphic expression within the human
      liver. We hypothesized that a single nucleotide polymorphism (SNP) in the 5'
      regulatory region of the CYP3A5 gene might be the cause of CYP3A5 polymorphic
      expression. Due to the existence of "CYP3AP1," a highly homologous sequence to
      the CYP3A5 gene, it was necessary to make specific primers to the CYP3A5 gene. In
      the present study, we designed a series of oligonucleotide primers for sequencing
      the proximal promoter region of the CYP3A5 gene in order to search for the
      putative regulatory single nucleotide polymorphism. We examined 86 established
      cell lines derived from Japanese individuals as a representation of the Japanese
      population. However, no SNP was detected in the promoter region of the CYP3A5
      gene isolated from the cell lines used, suggesting other causal factors for the
      observed polymorphism of CYP3A5-dependent drug metabolism.

PMID- 11510494
TI  - Suppressive effect of endogenous regucalcin on guanosine triphosphatase activity
      in rat liver nucleus.
AB  - The effect of regucalcin, a regulatory protein of Ca2+ signaling, on guanosine
      triphosphatase (GTPase) activity in the nuclei of rat liver was investigated.
      GTPase activity was significantly increased by the addition of CaCl2 (50 microm)
      in the enzyme reaction mixture. This increase was not seen in the presence of
      trifluoperazine (25 microM), an antagonist of calmodulin, which could decrease
      nuclear GTPase activity, suggesting that nuclear endogenous calmodulin is
      involved in an increase in the enzyme activity related to Ca2+ addition. The
      presence of regucalcin (0.5 microM) in the enzyme reaction mixture caused a
      significant decrease in nuclear GTPase activity. The enzyme activity was
      significantly raised in the presence of anti-regucalcin monoclonal antibody (25
      and 50 ng/ml) in the reaction mixture. This increase was completely abolished by
      the addition of regucalcin (0.5 microM). Also, the effect of regucalcin addition
      in increasing nuclear GTPase activity was seen in the presence of EGTA (0.1 mM),
      a chelator of Ca2+. The present study demonstrates that endogenous regucalcin has
      a suppressive effect on GTPase activity in the nuclei of rat liver.

PMID- 11510495
TI  - Wistar strain rats as the model for IgE antibody experiments.
AB  - The amount of plasma IgE antibody formed and its change over time were
      investigated by enzyme-linked immunosorbent assay (ELISA) in male and female
      Sprague-Dawley (SD), Donryu, and Wistar strain rats. IgE antibody formation was
      initiated by injecting a mixture of 2,4-dinitrophenylated ascaris extract (DNP
      As) as antigen and killed Bordetella pertussis as adjuvant into the paws of the
      animals. The amount of IgE antibody formed was low on day 10 in both male and
      female SD (40-80 ng/ml) and Donryu (20-40 ng/ml) strain rats, and an increase in
      the amount was observed on day 20. The peak value of IgE antibody was observed
      day 10 in Wistar strain rats and was 130 and 200 ng/ml in the male and female
      rats, respectively. These results suggest that Wistar strain rats produce the
      most IgE antibody when DNP-As is used as antigen and they can serve as a model
      for allergic diseases.

PMID- 11510496
TI  - Suppressive effect of aspirin on chromosome aberration induced by mitomycin C in
      mice.
AB  - Chromosome aberrations induced by mitomycin C (MMC) were suppressed by aspirin in
      a mouse micronucleus test with peripheral blood and bone marrow cells. Aspirin at
      doses of 0.5, 5, and 50 mg/kg was injected intraperitoneally or per administered
      orally 0.5, 6, or 24 h after administration of MMC and then peripheral blood
      and/or bone marrow cells were sampled 48 h after administration of MMC. The
      suppressive effect of aspirin was more pronounced in the aspirin-treated groups
      24 h than 0.5 and 6 h after administration of MMC. In the aspirin-treated group
      at 24 h, the frequency of polychromatic erythrocytes with micronuclei was
      decreased by about 60-80% after intraperitoneal injection and by about 40-70%
      after oral administration. It is suggested that aspirin may directly act on MMC
      metabolites, but not on MMC itself.

PMID- 11510497
TI  - Determinations of morin, quercetin and their conjugate metabolites in serum.
AB  - Morin and quercetin are isomeric antioxidant flavonols. High-performance liquid
      chromatographic methods were developed for the quantitation of morin and
      quercetin in serum. The method employed a Cosmosil RP-18 column, using
      acetonitrile/0.2% o-phosphoric acid 28/72 and 27/73 (v/v) as mobile phases, with
      ethyl paraben and 6,7-dimethoxycoumarin used as internal standards for morin and
      quercetin, respectively. Moreover, a strategy to stabilize morin/quercetin
      released from their glucuronides/sulfates in serum during hydrolysis was
      established. The present methods are applicable for determining morin, quercetin,
      and their glucuronides/sulfates in serum.

PMID- 11510498
TI  - Stability of a cisplatin-chondroitin sulfate A complex in plasma and kidney in
      terms of protein binding.
AB  - To assess the stability of a cisplatin (CDDP) complex prepared with chondroitin
      sulfate A (CSA) relative to protein binding in the circulation and kidney, a
      trichloroacetic acid (TCA) precipitation method was developed to measure the
      protein-unbound species of CDDP and the CDDP-CSA complex in plasma and kidney
      homogenates. The total and unbound drug concentrations were determined up to 3 h
      following a 2 mg/kg bolus injection of CDDP or CDDP-CSA complex to rats. The
      stability against plasma binding was evaluated by a determination of the area
      under concentration-time curve from time 0 to infinite time (AUC(0-infinity));
      the ratio of unbound drug AUC(0-infinity) to total drug AUC(0-infinity) was
      employed to estimate the availability of the unbound drug in the circulation. The
      results showed that a competitive reaction to platinum existed between plasma
      protein and the CDDP-CSA complex, but the complex accounted for more than 60% of
      the protein-unbound species for a dosage, compared to 30% obtained by an
      administration of uncomplexed CDDP. The tissue binding kinetics in kidney for
      CDDP and the CDDP-CSA complex was investigated by the use of homogenates. The
      binding rate constants of CDDP and CDDP-CSA in a kidney homogenate were 0.0040
      min(-1) and 0.0014 min(-1), respectively. The results indicate that the CDDP-CSA
      complex could effectively retard the binding of CDDP to protein in the kidney.
      These data provide evidence that endogenous protein is able to compete for
      platinum from the CDDP-CSA complex, but the complex effectively retarded the
      protein binding reaction with CDDP in plasma and kidney as compared to native
      CDDP, which has the potential for reducing the accumulation of CDDP in plasma and
      kidney.

PMID- 11510500
TI  - Comment on: The EUSOMA Position Paper on the requirements of a specialist breast
      unit, Eur J Cancer 2000, 36, 2288-2293.

PMID- 11510501
TI  - Sentinel lymph nodes study in 30 cases of melanoma.
AB  - In 30 cases of melanoma, we attempted to detect sentinel lymph nodes using 1-2%
      patent blue dye and were able to detect them in 27 cases (90%): 19 cases out of
      21 cases in the groin area (90%), 5 out of 5 cases in the axilla area (100%), and
      3 out of 4 cases in the neck area (75%). The numbers of sentinel lymph nodes were
      one in 16 cases, two in 7 cases, three in 2 cases, and four in 2 cases. The cases
      with three and four nodes were all in the groin area. In 22 cases, tumor
      metastasis was negative in sentinel lymph nodes. Sentinel lymph nodes were
      detected in 36 out of 174 samples, and tumor metastasis was negative except in
      these sentinel lymph nodes (false negative 0%). In the groin area, sentinel lymph
      nodes were located around the femoral and great saphenous vein junction. In the
      axilla area, sentinel lymph nodes were located in the central, lateral and
      subscapular lymph nodes. In the head and neck area, sentinel lymph nodes were
      found in the submandibular and occipital lymph nodes. The positions of sentinel
      lymph nodes differed a little with tumor location. By accumulating cases, it
      should become possible to predict the positions of sentinel lymph nodes before
      operations. Sentinel lymph node biopsy is easy and requires only a small
      incision.

PMID- 11510502
TI  - Sexual habits and clinico-etiological profile of sexually transmitted diseases in
      Nepal.
AB  - A total of 100 patients giving histories suggestive of sexually transmitted
      disease (STDs) and attending the dermatology OPD at BPKIHS (B.P. Koirala
      Institute of Health Sciences) in Nepal over a period of one year from 1st July
      1999 to 30th June 2000 were included in this study. Out of 10,400 new dermatology
      cases, a total of 100 cases (0.96%) of STDs were seen. Of these 73 were males,
      and the majority (53%) were in the age group of 21-30 years. Most of the patients
      were from Sunsari district (54%). The most common profession (21%) was
      businessman followed by housewife (19%). The most common age for first sexual
      contact was 16 to 19 years (45%). Eleven percent had their first sexual contact
      at the age of 15 or below 15 years. Premarital sexual exposure was recorded in
      17% of the unmarried males. There were only 3 homosexuals and 1 bisexual patient.
      Multiple contacts were recorded in 55% of the patients. The most common source of
      contact was a commercial sex worker in 34.15%. Condoms were always used by only
      7%. The various types of sexually trasmitted diseases (STDs) were syphilis (31%)
      followed by condylomata acuminata (16%), herpes genitalis (15%), gonorrhoea (9%),
      and mixed infections (12%). Despite their varied sexual behavior, none of the
      patients were HIV positive; however, it is always advisable to screen all STD
      patients for HIV antibody.

PMID- 11510504
TI  - Lupus vulgaris mimicking lichen simplex chronicus.
AB  - Cutaneous tuberculosis is not an uncommon entity but it often remains undiagnosed
      and is inappropriately treated due to its varied presentation. We present a 42
      year-old male with lupus vulgaris in the perianal area, who was treated as lichen
      simplex chronicus with steroids for two years. With four drug antitubercular
      treatment, the patient had a dramatic response. The case is being reported
      because in this HIV era with the resurgence of tuberculosis, not only will there
      be an increase in incidence but also more involvement of atypical sites.

PMID- 11510503
TI  - Analysis of the vascularity of an atelocollagen sponge substitute dermis in the
      human.
AB  - Atelocollagen sponge had been developed as a new beneficial dermal substitute.
      However, histologic studies of the vascularity of an atelocollagen sponge
      substitute dermis in humans are very rare. The purpose of this study was to
      determine the distribution of blood vessels in an artificial dermis made of
      atelocollagen affixed to human tissue. The artificial dermis was used in 21 cases
      and at 23 sites, and biopsies were performed. The samples were stained with anti
      human blood type A, B, and H monoclonal antibodies. Angiogenesis in the upper
      layer of the artificial dermis was recognizable within 14 days after affixing the
      artificial dermis. We concluded that a skin graft taken 14 days after affixing
      the artificial dermis would be successful, even though the granulation tissue
      formation might not be completed and the color would most likely remain white.
      The lower layer of the angiogenesis spread in a horizontal direction like an
      expanded network of blood vessels, while the middle and upper layers of
      angiogenesis spread perpendicularly to form upward growth when two cases were
      examined in various spots. The data suggested that the sponge construction of
      artificial dermis not only became a scaffold for the invasion of collagen, but it
      also facilitated construction of near normal dermis with regard to the
      construction of blood vessels.

PMID- 11510505
TI  - Successful treatment of a patient with lymphomatoid papulosis by methotrexate.
AB  - We report a case of lymphomatoid papulosis (LyP) that occurred in a 44-year-old
      Japanese male patient. Reddish papules with a small number of pustules and
      nodules were observed on the extremities, chest and upper back. Most lesions were
      also associated with central necrosis, ulceration and crusting, and regressed
      spontaneously within 4 to 6 weeks. Histopathological examination revealed wedge
      shaped dense cellular infiltrate in the dermis, which was mixed with large
      atypical lymphoid cells, small lymphocytes, eosinophils and neutrophils. These
      large atypical cells expressed CD30 on their cell membrane and cytoplasm.
      Rearrangement of the T-cell receptor (TcR) beta-chain gene was detected in the
      skin lesion. Lymphadenopathy with histopathologic change similar to the skin
      lesions, but without TcR gene rearrangement, was found at the left inguinal area.
      Systemic administration of methotrexate (7.5-15.0 mg/week) was found to be
      dramatically effective in resolution of skin lesions and prevention of their
      recurrence.

PMID- 11510506
TI  - Infantile myofibromatosis with visceral involvement and complete spontaneous
      regression.
AB  - Infantile myofibromatosis is an unusual mesenchymal disorder characterized by the
      proliferation of tumors in the skin, muscle, bone, and viscera. Two types can be
      distinguished; the solitary type, defined by the presence of one nodule in the
      skin, muscle, bone or subcutaneous tissue; and the multicentric type which can be
      divided into two sub-types. In the first sub-type the lesions are multicentric
      but without visceral involvement, while in the second, visceral involvement is
      present. The prognosis of the disease depends on whether visceral involvement is
      present. Solitary and multicentric nodules without visceral involvement usually
      have excellent prognosis with spontaneous regression of lesions within 1 to 2
      years of diagnosis. On the other hand, visceral lesions are associated with a
      significant morbidity and mortality, resulting from vital organ obstruction,
      failure to thrive, or infection. Death in these cases often occurs at birth, or
      soon after, and is usually due to cardio-pulmonary or gastrointestinal
      complications. The case being reported here, is that of a female newborn who had
      multiple skin, subcutaneous tissue, skeletal muscle, bone, and lung lesions
      immediately after bith. At the age of three years, the child is in good health,
      her psychomotor development is in accordance with her age group, and the lesions
      have completely regressed. This is a case of the multicentic type of infantile
      myofibromatosis with visceral involvement, where all lesions have spontaneously
      regressed. This is a rarity since the prognosis in the majority of such cases is
      poor.

PMID- 11510508
TI  - A case of Kaposi's sarcoma associated with pemphigoid nodularis.
AB  - Pemphigoid nodularis is a rare variant of bullous pemphigoid. Bullous pemphigoid
      complicated by internal malignancy has been well documented. There have been only
      a few reported cases of bullous pemphigoid associated with Kaposi's sarcoma. We
      described a case of pemphigoid nodularis who later developed Kaposi's sarcoma
      that might be related to immunosupressive therapy, a situation that has not been
      reported previously.

PMID- 11510507
TI  - A case of cutaneous low-grade myofibroblastic sarcoma.
AB  - A 28-year-old woman presented with a recurrent nodule on the lower margin of her
      left nostril after laser surgery. Histologically, the nodule had an indistinct
      margin and was composed of interlacing fascicles of plump, spindled or stellate
      tumor cells with mild cytologic atypia. The tumor cells were revealed to be
      myofibroblasts by positivity to smooth muscle actin and negativity to desmin. A
      diagnosis of low grade myofibroblastic sarcoma (LGMS) was made.

PMID- 11510509
TI  - Professional organizations: changes and relationships.

PMID- 11510510
TI  - Long-term comparative mortality in hyperthyroid patients treated with radio
      iodine, a cohort study in England.
AB  - BACKGROUND: The focus of this long-term study (entry 1950-1989, follow-up to
      1996) on hyperthyroid patients treated with 131I was on all-cause mortality and
      some specific causes other than cancer. The study was carried out on 7209
      patients who were residents of the Midlands area around Birmingham, England. In a
      total exposure of 105,028 patient-years, 3611 deaths were observed, compared with
      3186 deaths expected from age/sex-matched rates in the English life tables.
      RESULTS: Data were reported for observed and expected deaths, and SMR values
      (standardized mortality ratios to one decimal place) by selected causes of death
      in combinations with duration, age, and 3 dosage groups of 131I. Exposure data
      were given only for the dosage groups of 131I, not for the results by age or
      duration. CONCLUSIONS: Comparative mortality was significantly increased for all
      cause mortality (but with an SMR of only 1.13), and also for cardiovascular and
      cerebrovascular deaths, and deaths from fracture. Excess mortality was greatest
      in the first year after entry, and decreased thereafter. There was no reported
      increase in cancer mortality.

PMID- 11510511
TI  - Long-term comparative cancer mortality after use of radio-iodine in the treatment
      of hyperthyroidism, a fully reported multicenter study.
AB  - BACKGROUND: The Cooperative Thyrotoxicosis Therapy Follow-up Study reported
      cancer mortality after use of radio-iodine (131I), surgery, and other treatments
      in patients with hyperthyroidism, started during 1946-1964 and followed through
      1968. In 1984, the National Cancer Institute initiated a continued follow-up (FU)
      of the same cohort through 1990, to assess potential carcinogenic effects of 131I
      through 1990, a potential FU ranging from 26 to 44 years. RESULTS: With an
      initial cohort of 35,630 hyperthyroid patients, a mean entry age of 46 years and
      738,831 patient-years of FU, the 2950 observed cancer deaths were only minimally
      over the 2858 expected cancer deaths from US population rates, after exclusion of
      first-year deaths. In the 64.7% of patients receiving 131I, the total cancer
      deaths were significantly above expected (258 versus 208), only at durations of 1
      5 years, not thereafter. Thyroid cancer deaths were significantly elevated, but
      the number was very small, only 24 deaths in all exposures, as compared with 5.89
      expected. The overall thyroid cancer mortality was higher in cases of toxic
      nodular goiter than in patients with Graves' disease. CONCLUSIONS: Despite the
      small early increase in total cancer deaths and the relatively higher increase in
      thyroid cancer deaths (only 18 excess deaths), the authors conclude that therapy
      with the doses of 131I used is a safe procedure. The interpretation of cause
      specific excess mortality is greatly influenced by the prevalence of the cause of
      death.

PMID- 11510512
TI  - Long-term morbidity and mortality in Chinese insurance applicants infected with
      the hepatitis B virus.
AB  - BACKGROUND: Worldwide, there are approximately 350 million carriers of the
      hepatitis B virus (HBV). The protracted course of HBV infection makes it
      difficult to estimate morbidity and mortality risk in an insured lives population
      that is chronically infected with HBV because most studies on this topic have
      been based on older patients with advanced disease who were treated at tertiary
      centers that specialize in care of patients with liver disease. Data from these
      reports bias risk estimates toward severe cases and are not appropriate
      indicators of what might be expected in an insurance context. This article
      discusses use of a Markov model to estimate long-term morbidity and mortality
      risk associated with chronic HBV infection in otherwise healthy Chinese insurance
      applicants. RESULTS: The model was validated by comparing results to population
      data published in Taiwan, Hong Kong, Shanghai, Singapore, and Korea. For males,
      mortality ratios were in the range of 150-175% for underwriting ages 20, 30, and
      40 and slightly lower for age 50. For females, mortality ratios were in the range
      of 125-150% and slightly higher for age 50. Higher mortality ratios in males were
      related to the fourfold higher hepatocellular carcinoma (HCC) incidence rate.
      Mortality ratios varied with the extent of the underwriting evaluation. Liver
      related morbidity incidence increased with age at underwriting for males and
      females. HBeAg (hepatitis B "e" antigen)/anti-HBe status was not a major factor
      for differentiating risk in an insurance context. CONCLUSION: Morbidity and
      mortality are within the insurable range for the majority of HBV-infected Chinese
      applicants. Risk varies with the extent of the underwriting evaluation and the
      percentage of applicants with significant liver fibrosis or early cirrhosis that
      are detected during the underwriting process. HBeAg/anti-HBe status is not a
      major factor for differentiating risk in an insurance context. Morbidity and
      mortality estimates provided by the model can be generalized to other populations
      and individuals where HBV infection occurs at birth or during early childhood,
      although some modification in insurance risk might be required in non-Asian
      markets.

PMID- 11510513
TI  - Peripartum cardiomyopathy: mortality outcomes.
AB  - Mortality estimates of peripartum cardiomyopathy have been reported to be between
      18 and 56% without reference to time frames. Although this is an unusual
      impairment, medical directors need accurate information to meet the gold standard
      of underwriting: decisions must be based on sound underwriting and actuarial
      principles reasonably related to actual or anticipated loss experience. In an
      insurance purchasing population, the excess mortality in peripartum
      cardiomyopathy can be nearly eliminated by not insuring those with the impairment
      within the first 6 months postpartum or until all abnormal physiologic parameters
      have resolved. Thereafter, the risk is probably negligible. This abstract
      illustrates the challenge to determine expected mortality when the study
      population exhibits strong racial diversity and when available expected life
      tables contain raw data of only alive and dead at each yearly interval.

PMID- 11510514
TI  - Assessing impairment and disability for syndromes presenting with chronic
      fatigue.
AB  - Many disability claims are based on the subjective symptom of fatigue, which can
      be caused by a wide spectrum of diagnoses including fibromyalgia, chronic fatigue
      syndrome and cardiopulmonary diseases. Chronic pain is very often a compounding
      problem. It is vital for every insurer to have fair and objective criteria to
      distinguish between invalid claims and those with merit. This review article
      proposes objective tools and parameters to achieve this goal.

PMID- 11510515
TI  - A new century approach for alcohol screen in the insurance industry.
AB  - Several recent studies point to the value of using combinations of biochemical
      markers for the identification of alcohol abuse. The Early Detection of Alcohol
      Consumption (EDAC) test uses a statistical method that combines the results of
      several routine laboratory tests to form a metabolic fingerprint for each
      subject. In this study, we evaluated the use of the EDAC test as a screening tool
      to assess heavy drinking in insurance applicants. The EDAC was calculated by
      linear discriminate function analysis using the results of 14 routine tests
      including liver enzymes, lipids, proteins, and blood sugars. We collected and
      analyzed 1680 random samples at Heritage Laboratories (Olathe, Kan). Alcohol
      Detection Services (Brookfield, Wis) and Millennium Strategies (Madison, Wis)
      collaborated in the data analysis and interpretation of laboratory tests results.
      Ninety-three percent of applicants showed a negative EDAC test. The 7% (n = 134)
      who screened positive for the EDAC test were then reflexed to carbohydrate
      deficient transferin (CDT) and whole blood associated acetaldehyde (WBAA).
      Sixteen percent (22/134) showed a positive confirmatory test. Among these 16% of
      subjects, 41% (9/22) showed no elevations in liver enzymes or HDL-C results. Four
      of these subjects were among the top one third with the highest elevations for
      the CDT test in the entire group and one of them was positive for both the CDT
      and WBAA tests. These results suggest that the EDAC screen may provide an
      efficient alternative screening tool for the identification of heavy alcohol
      consumption not HBA as it identifies applicants with both normal or abnormal
      liver enzymes and HDL-C.

PMID- 11510516
TI  - Prostate cancer.
AB  - Prostate cancer is the most common internal cancer in American males. There are
      many variables that effect prognosis, with the Gleason scoring system being one
      of the most important factors. There is controversy regarding the ideal treatment
      in various subsets of prostate cancer patients. Posttreatment prostate specific
      antigen values have prognostic significance.

PMID- 11510517
TI  - A jammed finger from basketball.
AB  - A benign enchondroma of the left fifth distal interphalangeal joint occurred in a
      39 year old male. The differential diagnoses and outcomes are discussed.

PMID- 11510518
TI  - Sentinel lymph node biopsy for breast cancer.
AB  - The regional lymph node status is the most powerful predictor of survival in
      women with invasive breast cancer.

PMID- 11510519
TI  - Cardiovascular disease and mortality in older adults with small abdominal aortic
      aneurysms detected by ultrasonography: the Cardiovascular Health Study.

PMID- 11510520
TI  - Diabetes and all-cause and coronary heart disease mortality among US male
      physicians.

PMID- 11510522
TI  - Long-term outcome in asymptomatic men with exercise-induced premature ventricular
      depolarizations.

PMID- 11510521
TI  - Urine detection of survivin and diagnosis of bladder cancer.

PMID- 11510523
TI  - Should the actual or the corrected serum sodium be used to calculate the anion
      gap in diabetic ketoacidosis?

PMID- 11510524
TI  - Noninvasive positive pressure ventilation in acute respiratory failure: does it
      improve outcomes?
AB  - Studies have shown that noninvasive positive pressure ventilation (NPPV) is well
      tolerated and safe, and that it improves oxygenation in some patients with acute
      respiratory failure. By obviating the need for endotracheal intubation in certain
      conditions, it results in fewer complications, shorter hospital stays, and
      consequently, lower mortality rates and costs of care.

PMID- 11510525
TI  - Should we still be using theophylline to treat asthma?

PMID- 11510526
TI  - Heat illness: tips for recognition and treatment.
AB  - Heat stroke, an acute, life-threatening emergency, results from an overload or
      impairment of heat-dissipating mechanisms. At risk are the elderly, infants, the
      obese, people with hyperthyroidism, and those taking certain drugs. Early
      recognition and rapid cooling are essential--the more rapid the cooling, the
      lower the mortality.

PMID- 11510527
TI  - Myocardial infarction in a 24-year-old woman.

PMID- 11510528
TI  - Prevention and treatment of pressure ulcers: what works? what doesn't?
AB  - Although no gold standard for preventing or treating pressure ulcers has been
      established, data from clinical trials indicate specific efforts are worthwhile.
      Preventive strategies include recognizing risk, decreasing the effects of
      pressure, assessing nutritional status, avoiding excessive bed rest, and
      preserving the integrity of the skin. Treatment principles include assessing the
      severity of the wound; reducing pressure, friction, and shear forces; optimizing
      wound care; removing necrotic debris; managing bacterial contamination; and
      correcting nutritional deficits.

PMID- 11510529
TI  - Update on peripheral vascular diseases: from smoking cessation to stenting.
AB  - Newer pharmacologic agents including gene therapy hold promise for the treatment
      of atherosclerotic peripheral vascular disease (PVD), as do advances in
      endovascular revascularization techniques. Nonetheless, the two most important
      treatments remain the same: stopping smoking and starting a walking program.

PMID- 11510531
TI  - Peripheral vascular disease.

PMID- 11510532
TI  - Molecular recognition in imprinted polymers: thermodynamic investigation of
      analyte binding using microcalorimetry.
AB  - This study aimed at elucidating the interaction mechanism between an imprinted
      polymer and its template in aqueous environment with thermodynamic aspects. The
      herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) was chosen as a model template
      to imprint a co-polymer of 4-vinylpyridine (4-VP) and ethyleneglycol
      dimethacrylate. Equilibrium binding isotherm analysis and isothermal titration
      microcalorimetry were used to quantify the contribution of enthalpy and entropy
      to the binding process, identify the nature of the interactions involved and
      confirm the existence of binding pockets with shape-complementarity to the
      template. For the binding process of 2,4-D to the imprinted polymer, we postulate
      three subprocesses: (1) dehydration of the binding pocket and of the 2,4-D, (2)
      adsorption of 2,4-D, and (3) rearrangement of the water molecules from the
      dehydration process. We found that binding in aqueous environment was due to the
      cumulative effect of pi-stacking and electrostatic interactions between the
      template and the functional monomers. At pH<6, entropy is the dominating driving
      force, while at pH>6 where the highest difference in binding between the
      imprinted and a non-imprinted reference polymer was observed, the enthalpy change
      accounts for most of the binding free energy. The developed microcalorimetric
      method sheds light on the binding mechanism of analyte molecules with imprinted
      polymers, in particular if the polymers are used in aqueous solvents.

PMID- 11510533
TI  - Reversed-phase separation of basic tricyclic antidepressants using buffered and
      fluoroform-enhanced fluidity liquid mobile phases.
AB  - In an effort to expand the range of applications of enhanced-fluidity liquid
      chromatography (EFLC) to strongly polar and basic analytes, fluoroform (CHF3) was
      investigated as a fluidity-enhancing agent. Fluoroform was chosen due to its high
      polarity, low viscosity and chemical inertness toward water and basic analytes. A
      group of representative basic compounds, tricyclic antidepressants, covering a
      wide range of polarity was chosen as model compounds. Their retention behavior on
      a C18 stationary phase in methanol/phosphate buffer and methanol/phosphate
      buffer/CHF3 mobile phases was characterized. The chromatographic performance with
      mobile phase conditions of different pH, with and without CHF3 addition and with
      addition of triethylamine was studied. The advantages of using CHF3 enhanced and
      buffered mobile phases were shown in the much improved chromatographic
      performance, such as shortened analysis time, increased efficiency, lower
      pressure drop and improved selectivity. Furthermore, this study demonstrated for
      the first time, that a commercial instrument could be readily utilized for EFLC
      separations which greatly expands the application range of the EFLC technique and
      chromatographic instrumentation.

PMID- 11510534
TI  - Size- and shape-dependent separation of TiO2 colloidal sub-populations with
      gravitational field flow fractionation.
AB  - The simplest field flow fractionation technique, which uses the earth's gravity
      as the external field is applied to isolate two populations, which differ in both
      shape and size, from a polydisperse sub-micron TiO2 powder of homogenous density.
      The fraction eluted first is spherical with an average diameter of 0.31 microm
      while the second fraction is ellipsoidal and can be associated with a 0.45 microm
      hydrodynamic diameter. Elution conditions appeared to be very sensitive to
      electrolyte and surfactant characteristics in the carrier phase as well as on the
      sample concentration. Using 25 microl (1%, w/w) sample suspension, separations of
      spherical from ovoid particles was performed in almost 2 h with a mobile phase of
      0.001 M KNO3-0.01% (v/v) Fl-70 in water in a 0.025-cm thick channel made of
      polystyrene walls.

PMID- 11510535
TI  - Partition coefficients of alkyl aromatic hydrocarbons and esters in a hexane
      acetonitrile system.
AB  - Partition coefficients (Kp) in a heterogeneous system consisting of two
      immiscible organic solvents can be successfully used for a supplementary
      identification parameter in qualitative GC and GC-MS analysis of organic
      compounds. For rapid addition to database of Kp values, calculation methods based
      on the well-known 'retention-structure relationships' approach can be used. This
      paper reports the experimentally determined and calculated Kp values for 252
      compounds including alkyl aromatic hydrocarbons and esters. It is shown that for
      group identification of components it is desirable to use not the Kp values
      themselves but the parameter j which is a combination of K, and gas
      chromatographic retention indices: j = kI - log Kp.

PMID- 11510536
TI  - Comparison of methods employing gas chromatography retention data to determine
      vapour pressures at 298 K.
AB  - Validity of five models suggested for expressing the relationship between vapour
      pressures and GC retention times measured on a non-polar capillary column were
      tested on a common set of compounds [five homologous series of the type H-(CH2)n
      Y, where Y denotes Cl, Br, CHO, OCOCH3 and COOCH3, and n varies from 6 to 14].
      Standard methods of statistical analysis, as well as vapour pressure values
      obtained independently from direct vapour pressure measurements were used as
      validity criteria. For the 40-compound data set examined, the methods provided
      vapour pressures agreeing within 9.2-24.7% (average absolute percent error) with
      direct experimental data.

PMID- 11510537
TI  - Experimental determination and prediction of the gas-liquid n-hexadecane
      partition coefficients.
AB  - Experimental methods based on gas-phase chromatography were tested with a view to
      determine the gas-liquid n-hexadecane partition coefficients, log L16 of non
      volatile compounds at 298.2 K. It was demonstrated that reliable values of log
      L16 of compounds more volatile than n-docosane can be obtained using either
      capillary, or packed columns. The main limitation of both methods is the column
      stability at high temperatures. Here we propose a new method based on the
      temperature gradient mode, to obtain log L16 of high-boiling compounds. A group
      contribution model is also presented in view to predicting log L16 values of non
      volatile compounds.

PMID- 11510538
TI  - Polycyclic aromatic hydrocarbon 13C/12C ratio measurement in petroleum and marine
      sediments application to standard reference materials and a sediment suspected of
      contamination from the Erika oil spill.
AB  - This paper describes a simple and rapid sample preparation procedure allowing to
      measure the stable carbon isotopic composition of polycyclic aromatic
      hydrocarbons (PAHs) in petroleum and in sediments. The aromatic fraction is first
      purified and isolated on alumina and silica micro-columns. A high-performance
      liquid chromatography fractionation allows one then to isolate each aromatic
      family in order to limit coelutions between PAHs. Moreover, this purification
      step reduces the importance of the unresolved complex mixture which otherwise
      contribute to the GC-isotope ratio MS background signal. The application of this
      analytical procedure has allowed one to determined PAH isotopic composition in a
      reference material crude oil (SRM 1582) and a marine sediment (SRM 1944) with
      good reproducibility as uncertainties between three independent assays performed
      were lower than 0.5 per thousand. This analytical procedure has then been
      successfully applied to confirm the contamination of a sediment by the petroleum
      product spilled by the Erika tanker after its wreck on 12 December 1999 close to
      the Atlantic Coast of France.

PMID- 11510539
TI  - Monolithic silica sorbents for the separation of diastereomers by means of
      simulated moving bed chromatography.
AB  - Monolithic silica sorbents with a dual pore system can be used in preparative
      chromatography for the separation of diastereomers. They exhibit some special
      features, which allows them to be operated at high linear velocities due to their
      reduced pressure drop and fast diffusion kinetics. Especially in the continuous
      set-up of simulated moving bed chromatography monolithic sorbents show high
      productivities, which make them well suited in pharmaceutical drug development
      for the production of pure isomers.

PMID- 11510540
TI  - Protocol for the determination of selected neutral and acidic semi-volatile
      organic contaminants in fish tissue.
AB  - Progress toward the development of a protocol for the determination of a broad
      spectrum of organic compounds in fish tissue is reported. Finely ground and
      homogenized fish tissue samples were Soxhlet extracted. Phenolic compounds in the
      extracts were acetylated and the derivatized extract containing the acetates and
      neutral semi-volatiles was cleaned up with silica gel and size-exclusion column
      chromatography. These semi-volatile organic compounds were determined by gas
      chromatography-mass spectrometry. The method is evaluated for recovery and
      precision of selected analytes during the analysis of over 300 fish tissue
      samples of varying species in support of contaminant determination in fish tissue
      from the Columbia/Snake River watershed.

PMID- 11510541
TI  - Comparison of subcritical water and organic solvents for extracting kava lactones
      from kava root.
AB  - Subcritical water extraction of lactones from a kava (Piper metlhysticum) root
      was compared to a Soxhlet extraction with water, to boiling in water, and to a
      sonication in acetone. For ground kava (250-500 microm), 2 h of subcritical water
      extraction were required for a complete extraction at 100 degrees C, while at 175
      degrees C, 20 min were sufficient. For a complete extraction of the unground
      (shredded) kava, the time of extraction was extended to 40 min at 175 degrees C.
      Boiling for 2 h and extraction with Soxhlet apparatus for 6 h, both of which
      employed water at atmospheric pressure, produced yields 40-60% lower than those
      obtained with subcritical water. With unground kava, 40 min of subcritical water
      extraction yielded essentially the same recoveries of lactones as 18 h of
      sonication with acetone, methylene chloride, or methanol.

PMID- 11510542
TI  - Analysis of estrogens in river water and effluents using solid-phase extraction
      and gas chromatography-negative chemical ionisation mass spectrometry of the
      pentafluorobenzoyl derivatives.
AB  - A procedure was developed for the analysis of estrogens in environmental water
      and effluents. Samples were extracted by passing through polymer-impregnated
      solid-phase extraction discs or C18 cartridges, followed by gas chromatography
      negative chemical ionisation mass spectrometry of the pentafluorobenzoyl
      derivatives. The derivatives were stable and gave diagnostic negative molecular
      ions as the base peak for each of the major estrogens studied. The absolute
      recovery of estrogens spiked into clean groundwater using the disc procedure was
      84-116% at the 10 ng l(-1) level (calculation not based on use of internal
      standards). Using doubly deuterated estradiol as internal standard added prior to
      extraction, the % relative standard deviation of estrogen extraction and analysis
      in spiked groundwater at the 10 ng(-1) level was 2.6-9.8%. Detection limits were
      0.2 ng l(-1) or below for the major estrogens, based on a 2.5 litre sample. The
      most abundant estrogen was estrone, with concentrations over the range 6.4-29 ng
      l(-1) in effluents, and 0.2 to 17 ng l(-1) in water from the River Thames.

PMID- 11510543
TI  - Fast analysis of important wine volatile compounds development and validation of
      a new method based on gas chromatographic-flame ionisation detection analysis of
      dichloromethane microextracts.
AB  - A method for the simultaneous determination of major (10-200 mg/l) and minor (0.1
      10 mg/l) volatile compounds from wine has been optimised and validated. A 3-ml
      volume of wine is diluted with water (7 ml), salted with 4.5 g of ammonium
      sulfate and extracted with 0.2 ml of dichloromethane. The extract is injected in
      the split mode in a GC system, separated on a Carbowax 20M capillary column and
      detected by flame ionisation detection. Volatiles from wine are divided into four
      groups according to their behaviour in the extraction, and a specific internal
      standard has been selected for each group. The method allows satisfactory
      determination of more than 30 volatile compounds of wine. Compounds analysed
      include acetaldehyde, diacetyl, acetoine (3-hydroxy butanone), fusel alcohols and
      their acetates, and fatty acids and their ethyl esters. The linear dynamic range
      of the method covers the normal range of occurrence of analytes in wine and
      extends from at least one magnitude order to more than two, with typical r2
      between 0.9938 and 0.9998. Reproducibility ranges from 3.1 to 10% (as RSD) with
      5.5% as the average. The analysis of spiked samples has shown that matrix effects
      do not significantly affect method performance.

PMID- 11510544
TI  - Preparation and characterization of monolithic polymer columns for capillary
      electrochromatography.
AB  - A series of micro-monolithic columns with different porosities were prepared for
      capillary electrochromatography (CEC) by in-situ copolymerization of butyl
      methacrylate, ethylene glycol dimethacrylate, and 2-acrylamido-2-methyl-1-propane
      sulfonic acid in the presence of a porogen in fused-silica capillaries of 100
      microm I.D. Different column porosities were obtained by changing the ratios of
      monomers to porogenic solvents. Columns were investigated and evaluated under
      both pressure-driven (high-performance liquid chromatography, HPLC) and electro
      driven (capillary electrochromatography, CEC) conditions. Each column exhibited
      different efficiency and dependency on flow velocity under electro-driven
      conditions. Abnormally broad peaks for some relatively bulky molecules were
      observed. Possible explanations are discussed. The differences in column
      efficiency and retention behavior between the two eluent-driven modes were
      studied in detail. In addition, other column properties, such as morphology,
      porosity, stability and reproducibility, were extensively tested.

PMID- 11510545
TI  - Mechanistic study of enantiomeric recognition of primary amino compounds using an
      achiral crown ether with cyclodextrin by capillary electrophoresis and nuclear
      magnetic resonance.
AB  - A model and theoretical equations are presented to investigate the enantiomeric
      recognition mechanism of primary amino compounds using an achiral crown ether
      with cyclodextrin by capillary electrophoresis (CE) and nuclear magnetic
      resonance (NMR). Association constants were calculated from CE and 1H NMR
      experiment results on the basis of the model and the equations. The key step of
      chiral recognition was identified from those values. Using CE analyses of three
      primary amino compounds [1-(1-naphthyl)ethylamine; 1-aminoindan; 1,2,3,4
      tetrahydro-1-naphthylamine], the key step was identified with the equilibrium
      where the complex of a primary amino compound and 18-crown-6 becomes associated
      with 2,6-di-O-methyl-beta-cyclodextrin for all the three compounds. From the 1H
      NMR analyses of 1-(1-naphthyl)ethylamine, the key step was identified with the
      equilibrium where the complex of 1-(1-naphthyl)ethylamine and 18-crown-6 becomes
      associated with beta-cyclodextrin.

PMID- 11510546
TI  - Separation and selectivity of benzophenones in micellar electrokinetic
      chromatography using sodium dodecyl sulfate micelles or sodium cholate modified
      mixed micelles.
AB  - The separation and selectivity of nine benzophenones in micellar electrokinetic
      chromatography (MEKC) using sodium dodecyl sulfate (SDS) micelles or sodium
      cholate (SC) modified mixed micelles were investigated in the pH range 6.5-8.0.
      The results indicate that the combined effects of buffer pH and SC concentration
      can greatly affect the separation and selectivity of benzophenones, particularly
      for benzophenones possessing a hydroxyl substituent at the 4-position of the
      aromatic ring with respect to the carbonyl moiety when using SDS-SC mixed
      micelles. Better separability can be obtained with SDS-SC mixed micelles than
      with SDS micelles. Complete separation of nine benzophenones in MEKC can be
      achieved with an appropriate choice of buffer pH and the concentration of SDS
      micelles or SC modified mixed micelles. The dependence of the migration order of
      those benzophenones based on their structures and solute-micelle interactions is
      discussed.

PMID- 11510547
TI  - Quantitative determination of amygdalin epimers by cyclodextrin-modified micellar
      electrokinetic chromatography.
AB  - A new capillary electrophoresis method was developed for the quantitative
      determination of the amygdalin epimers, amygdalin and neoamygdalin, which are
      biologically significant constituents in the crude drugs, namely Persicae Semen
      and Armeniacae Semen. The effects of surfactants, additives and other analytical
      parameters were studied. As a result, the resolution of two epimers was performed
      by cyclodextrin-modified micellar electrokinetic chromatography with a buffer
      containing alpha-cyclodextrin and sodium deoxycholate. By the application of this
      method, a simple, fast and simultaneous quantitative determinations of amygdalin
      epimers in the crude drugs (Persicae Semen and Armeniacae Semen) and the Chinese
      herbal prescriptions (Keishi-bukuryo-gan and Mao-to) were achieved.

PMID- 11510548
TI  - Determination of puerarin, daidzein and rutin in Pueraria lobata (Wild.) Ohwi by
      capillary electrophoresis with electrochemical detection.
AB  - A method based on capillary electrophoresis with electrochemical detection was
      developed for the determination of puerarin, daidzein and rutin. Effects of
      several important factors such as the acidity and concentration of running
      buffer, separation voltage, injection time, and detection potential were
      investigated to acquire the optimum conditions. The working electrode was a 300
      microm diameter carbon disc electrode positioned opposite the outlet of
      capillary. The three analytes could be well separated within 12 min in a 40 cm
      length capillary at a separation voltage of 9 kV in a 50 mmol/l borate buffer (pH
      9.0). The relationship between peak currents and analyte concentrations was
      linear over about three orders of magnitude with detection limits (SIN=3) ranging
      from 0.241 x 10(-6) to 0.511 x 10(-6) mol/l for all compounds. This proposed
      method demonstrated long-term stability and reproducibility with relative
      standard deviations of less than 5% for both migration time and peak current
      (n=7). It has been successfully applied for the determination of puerarin,
      daidzein and rutin in Chinese traditional drugs, the vines of Pueraria lobata
      (Wild.) Ohwi and Puerariae Radix.

PMID- 11510549
TI  - Particle magnetic susceptibility determination using analytical split-flow thin
      fractionation.
AB  - Magnetic split-flow thin (SPLITT) fractionation is a newly developed S

PMID- 11510550
TI  - Conformational and temperature effects on separation of stereoisomers of a C3,C4
      substituted beta-lactamic cholesterol absorption inhibitor on amylose-based
      chiral stationary phases.
AB  - A direct liquid chromatography method was developed for the diastereo- and
      enantioselective analysis of a C3,C4-substituted beta-lactamic hypolipodemic
      agent (SCH 48461) and its stereoisomers on two commercially available amylose
      based chiral stationary phases (CSPs), namely, Chiralpak AS and Chiralpak AD. The
      mobile phase composition (type and content of alcoholic modifier) was considered
      to achieve baseline resolutions in a single chromatographic run. In order to
      investigate the influence of molecular flexibility on chiral recognition process,
      beta-lactams were ring-opened and converted into beta-amino esters derivatives.
      Thermodynamic parameters associated with adsorption equilibria between acyclic
      and cyclic stereoisomers and CSPs were calculated from chromatographic runs at
      various temperatures.

PMID- 11510551
TI  - Preparative separation of isoflavone components in soybeans using high-speed
      counter-current chromatography.
AB  - Four isoflavone components were purified from soybean extract by high-speed
      counter-current chromatography (HSCCC). Two types of multilayer coil separation
      columns were used: a small column made of standard 2.6-mm I.D. PTFE
      (polytetrafluoroethylene) tubing with a 260-ml capacity and a large column of
      convoluted PTFE tubing of 5.7-mm average I.D. with a 1,200-ml capacity.
      Separation was performed with a two-phase solvent system composed of hexane-ethyl
      acetate-1-butanol-methanol-acetic acid-water (1:2:1:1:5:1, v/v) by eluting the
      lower aqueous phase at 2 ml/min (small column) and 5 ml/min (large column) at a
      revolution speed of 700 rpm. From 500 mg of crude sample the small column yielded
      33 mg of daidzin, 41 mg of genistin, 27 mg of 6''-O-malonyldaidzin and 24 mg of
      6"-O-malonylgenistin. The large convoluted column separated, from 3 g of crude
      sample, 203 mg of daidzin, 241 mg of genistin, 158 mg of 6''-Omalonyldaidzin and
      135 mg of 6"-O-malonylgenistin all at over 90% purity. The convoluted tubing
      facilitated preparation of a large multilayer coil due to its high flexibility.

PMID- 11510552
TI  - Reversibly soluble macroaffinity ligand in aqueous two-phase separation of
      enzymes.
AB  - Use of alginate as a free bioligand incorporated in an aqueous two-phase system
      of polyethylene glycol 6000-salt resulted in considerable purification of wheat
      germ alpha-amylase and sweet potato beta-amylase from their crude extracts. The
      elution of the enzyme from the free bioligand was facilitated by exploiting the
      fact that alginate can be reversibly precipitated in the presence of Ca2+. alpha
      Amylase could be purified 42-fold with 92% activity recovery. beta-Amylase on the
      other hand could be purified 43-fold with 90% recovery. Both purified enzymes
      showed a single band on sodium dodecylsulfate-polyacrylamide gel electrophoresis.

PMID- 11510553
TI  - PH-Zone-refining counter-current chromatography of lappaconitine from Aconitum
      sinomontanum nakai I. Separation of prepurified extract.
AB  - pH-Zone-refining counter-current chromatography was applied to the separation of
      diterpenoid alkaloids from a crude sample from a crude prepurified sample
      containing lappaconitine at about 90% purity using a multilayer coil planet
      centrifuge. The experiment was performed with a two-phase solvent system composed
      of methyl tert.-butyl ether-tetrahydrofuran-distilled water (2:2:3, v/v) where
      triethylamine (10 mM) was added to the upper organic stationary phase as a
      retainer and hydrochloric acid (10 mM) to the aqueous mobile phase as an eluter.
      The separation of 10.5 g of the sample yielded 9.0 g of lappaconitine at a high
      purity of over 99% as determined by HPLC.

PMID- 11510554
TI  - Mass spectrometric detection in narrow-bore (0.10 mm i.d.) capillary
      chromatography fast, sensitive and selective analysis of polychlorinated
      biphenyls.
AB  - The combination of narrow-bore capillary gas chromatography with bench-top
      quadrupole mass spectrometric detection was evaluated for the determination of
      polychlorinated biphenyls (PCBs). The qualitative and quantitative performances
      of the system are illustrated by several analyses (PCB standards and human milk
      extracts). Capillary columns with different internal diameters (0.10, 0.18 and
      0.22 mm, respectively) were compared for their ability to separate PCB congeners
      and the analysis time. Short run times (less than 7 min) were sufficient for
      complete separation of PCB congeners on a 0.10-mm internal diameter (I.D.)
      capillary column without any loss of resolution when compared with a 0.22 mm I.D.
      column. Good qualitative and quantitative data acquisition was possible with
      quadrupole mass spectrometer for run times of 8 min, but incomplete peak reading
      was observed when run times were reduced to 3-4 min. Selected ion monitoring and
      dwell times of 10 ms are necessary to obtain detection limits for individual PCB
      congeners as low as 0.4 pg microl(-1) for standard solutions and 0.2 ng g(-1) fat
      for milk extracts. By using cold splitless injection, relatively high volumes (1
      microl) for narrow-bore capillaries could be injected without any peak
      distortion.

PMID- 11510555
TI  - Analysis of the volatile components of Argyranthemum adauctum (Link.) Humphries
      by gas chromatography-mass spectrometry.
AB  - The volatile constituents of the essential oil of Argyranthemum adauctum (Link.)
      Humphries extracted by steam distillation have been studied by GC-MS. A total of
      60 compounds have been identified representing the 89.8% of the oil. The major
      constituents were found to be beta-pinene (27.4%) and santolinatriene (22.6%).
      This is the first report on the chemical compounds of the oil of this species.

PMID- 11510556
TI  - Brominated flame retardants in laboratory air.
AB  - During the development of a method for determination of brominated flame
      retardants in human plasma and serum using solid-phase extraction, several
      brominated flame retardants were found in the procedural blanks. The contaminants
      originated most probably from the laboratory air. The brominated flame retardants
      were found to be adsorbed on glass surfaces and to be acquired using solid-phase
      sampling. 2,4,6-Tribromophenol, 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) and
      2,2',4,4',5-pentabromodiphenyl ether (BDE-99) were the most abundant brominated
      flame retardants in our laboratory air, however, large differences in
      contamination with respect to sampling time and place were observed.

PMID- 11510557
TI  - Dansyl amino acid enantiomer separation on a teicoplanin chiral stationary phase:
      effect of eluent pH.
AB  - The retention and separation of a series of D,L dansyl amino acids (used as test
      solutes) on a teicoplanin stationary phase were investigated over a wide range of
      mobile phase (citrate buffer-methanol, 90:10, v/v) pH. An approach based on the
      development of various equilibria was carried out in order to describe the
      retention behavior of the solute in the chromatographic system. The equilibrium
      constants corresponding to the transfer of the anionic and zwitterionic forms of
      the dansyl amino acids from the mobile to the stationary phase were determined.
      These values allowed one to explain the decrease in the retention factor and the
      associated increase in the separation factor as the eluent pH was increased.
      Thermodynamic parameter variations were calculated so that the driving forces of
      the solute association with the teicoplanin phase were derived. This approach
      indicated that the chiral discrimination was principally controlled by the
      interaction between the anionic form of the solute and the stationary phase.

PMID- 11510558
TI  - Solid-phase microextraction coupled to liquid chromatography for the analysis of
      phenolic compounds in water.
AB  - Solid-phase microextraction (SPME) coupled to high-performance liquid
      chromatography (HPLC) has been applied to the analysis of priority pollutant
      phenolic compounds in water samples. Two types of polar fibers [50 microm
      Carbowax-templated resin (CW-TPR) and 60 microm polydimethylsiloxane
      divinylbenzene (PDMS-DVB)] were evaluated. The effects of equilibration time and
      ionic strength of samples on the adsorption step were studied. The parameters
      affecting the desorption process, such as desorption mode, solvent composition
      and desorption time, were optimized. The developed method was used to determine
      the phenols in spiked river water samples collected in the Douro River, Portugal.
      Detection limits of 1-10 microg l(-1) were achieved under the optimized
      conditions.

PMID- 11510559
TI  - Separation of glyceride positional isomers by silver ion chromatography.
AB  - Separation of triglyceride and diglyceride positional isomers by silver ion high
      performance liquid chromatography coupled with an evaporative light-scattering
      detector is described. The triglyceride isomers had a fatty acid composition of
      CLC and CCL, where C and L were caprylic acid and linoleic acid, respectively.
      Diglyceride isomers, 1,2(2,3)-diglyceride and 1,3-diglyceride, which contained
      caprylic acid were separated too. A solvent system based on n-hexane, 2-propanol,
      ethyl acetate, and acetonitrile with a flow-rate of 0.8 ml/min was developed.
      Calibration curves of CLC and CCL were achieved with triolein as internal
      standard. Using this method, the incorporation of linoleic acid onto specific a
      position of glycerol backbone can be monitored.

PMID- 11510560
TI  - Separation of proteins using hydrophobic interaction membrane chromatography.
AB  - Membrane chromatography can overcome some of the problems associated with packed
      bed chromatography. In most membrane chromatographic studies reported so far, ion
      exchange and affinity interactions have been utilised. In this paper the use of
      hydrophobic interactions for chromatographic separation is described. A
      polyvinylidene fluoride membrane was identified which could bind specific
      proteins in the presence of high ammonium sulphate concentration. The separation
      of CAMPATH-IG monoclonal antibody and bovine serum albumin using this membrane is
      discussed.

PMID- 11510561
TI  - Purification of an oligonucleotide at high column loading by high affinity, low
      molecular-mass displacers.
AB  - The development of efficient techniques for large-scale oligonucleotide
      purification is of great interest due to the increased demand for antisense
      oligonucleotides as therapeutics as well as their use for target validation and
      gene functionalization. This paper describes the use of anion-exchange
      displacement chromatography for the purification of 20-mer phosphorothioate
      oligonucleotide from its closely related impurities using low-molecular-mass
      amaranth as the displacer. Experiments were carried out to examine the effect of
      the feed load on the performance of the displacement chromatography. In contrast
      to prior work, displacement chromatography was successfully scaled-up to high
      column loadings while maintaining high purity and yields. Experiments carried out
      on a Source 15Q column indicated that crude oligonucleotide loading as high as
      39.2 mg/ml of column were readily processed, resulting in product recovery of 86%
      and purity of 92%. These results demonstrate that anion-exchange displacement
      chromatography can indeed be employed for large-scale oligonucleotide separations
      at high column loading.

PMID- 11510562
TI  - Nonionic micellar liquid chromatography coupled to immobilized enzyme reactors.
AB  - Immobilized enzyme reactors are used as post-column reactors to modify the
      detectability of analytes. An immobilized amino acid oxidase reactor was prepared
      and coupled to an immobilized peroxidase reactor to detect low level of amino
      acids by fluorescence of the homovanilic dimer produced. A cholesterol oxidase
      reactor was prepared to detect cholesterol and metabolites by 241 nm UV
      absorbance of the enone produced. The preparation of the porous glass beads with
      the immobilized enzymes is described. Micellar liquid chromatography is used with
      non-ionic micellar phases to separate the amino acids or cholesterol derivatives.
      It is demonstrated that the non ionic Brij 35 micellar phases are very gentle for
      the enzyme activity allowing the reactor activity to remain at a higher level and
      for a much longer time than with hydro-organic classical chromatographic mobile
      phases or aqueous buffers. The coupling of nonionic micellar phases with
      enzymatic detection gave limits of detection of 32 pmol (4.8 ng injected) of
      methionine and 50 pmol (19 ng injected) of 20alpha-hydroxy cholesterol. The
      immobilized enzyme reactors could be used continuously for a week without losing
      their activity. It is shown that the low efficiency obtained with micellar liquid
      chromatography is compensated by the possibility offered by the technique to
      easily adjust selectivity.

PMID- 11510563
TI  - Determination of the herbicide 4-chloro-2-methylphenoxyacetic acid and its main
      metabolite, 4-chloro-2-methylphenol in water and soil by liquid chromatography
      electrospray tandem mass spectrometry.
AB  - A rapid and sensitive LC-electrospray tandem mass spectrometry method has been
      developed for the quantitation of 4-chloro-2-methylphenoxyacetic acid (MCPA) and
      4-chloro-2-methylphenol in both water and soil samples. Soil samples were
      extracted in alkaline media and cleaned-up by solid-phase extraction with C18
      cartridges before LC-MS analysis. The selectivity and sensitivity offered by the
      triple quadrupole allowed the direct injection of the water samples rendering a
      sample throughput of around 100 samples per day, without any sample pretreatment,
      rendering for MCPA a limit of detection of 40 ng/l. In order to increase the
      method sensitivity, mainly for metabolite, a previous solid-phase extraction step
      was also performed. The method was validated by means of recovery experiments
      using fortified water and soil samples, obtaining satisfactory recoveries for
      both compounds in water and for MCPA in soil. The validated procedures can be
      used for the specific monitoring of residues of MCPA and its main metabolite in
      environmental samples, as ground and surface waters and soils, providing more
      selectivity and sensitivity than the current UV-based methodology. Besides,
      sample manipulation is greatly reduced in comparison to other GC-MS based methods
      which require a previous derivatization.

PMID- 11510564
TI  - Preparative separation of isomeric 2-(2-quinolinyl)-1H-indene-1,3(2H)-dione
      monosulfonic acids of the color additive D&C Yellow No. 10 (quinoline yellow) by
      pH-zone-refining counter-current chromatography.
AB  - The main components of the color additive D&C Yellow No. 10 (Quinoline Yellow,
      Color Index No. 47005), 2-(2-quinolinyl)-1H-indene-1,3(2H)-dione-6'-sulfonic acid
      (6SA) and 2-(2-quinolinyl)-1H-indene-1,3(2H)-dione-8'-sulfonic acid (8SA), were
      isolated from the dye mixture by pH-zone-refining counter-current chromatography
      (CCC) in the ion-exchange mode. These positional isomers were separated from a
      portion of dye using sulfuric acid as the retainer acid and dodecylamine as the
      ligand (ion exchanger). The added ligand enhanced the partitioning of the
      hydrophilic components in the organic stationary phase of the two-phase solvent
      system that consisted of isoamyl alcohol-methyl tert.-butyl ether-acetonitrile
      water (3:1:1:5). Thus, separation of 1.8 g of D&C Yellow No. 10 using the above
      method resulted in 0.6 g of 6SA and 0.18 g of 8SA of over 99% purity. The
      isolated compounds were characterized by mass spectrometry and proton nuclear
      magnetic resonance with correlated spectroscopy assignments. The study
      exemplifies a new field of applications for pH-zone-refining CCC, to the
      separation of positional isomers of strongly hydrophylic compounds containing
      sulfonic acid groups.

PMID- 11510565
TI  - Method development for trace determination of poly(naphthalenesulfonate)-type
      pollutants in water by liquid chromatography-electrospray mass spectrometry.
AB  - A very sensitive analytical procedure based on LC-MS for determining trace
      amounts of the more relevant poly(naphthalenesulfonate) (PNS) contaminants
      present in environmental waters is presented. Extraction was performed on a
      styrene-divinylbenzene copolymer resin solid-phase extraction cartridge after
      addition of ammonium acetate to the sample. Small amounts of ammonium acetate in
      the mobile phase allowed the determination and characterisation of the four
      shorter oligomers by liquid chromatography-electrospray mass spectrometry. Under
      such conditions the electrospray process generates fully ionised molecules which
      greatly simplifies interpretation of spectra and quantitation. Additionally,
      confirmatory ions can be generated by the in-source collision-induced
      decomposition process. The effectiveness of the method was assessed in recovery
      experiments from drinking and river water samples spiked with commercial mixtures
      of PNS concrete plasticizers also referred as naphthalenesulfonate-formaldehyde
      condensates. Moreover, the performance of this method was compared to methods
      using ion-pair chromatography coupled with fluorimetric and mass spectrometric
      detection. Method detection limits were in the low picomolar range (1 ng/l for
      the monomer) for each isomer. In order to evaluate the environmental relevance of
      PNS type compounds waste, river and ground water grab samples were analysed.
      Concentrations of PNS oligomers detected in these samples ranged between 53 ng/l
      and 32 microg/l.

PMID- 11510566
TI  - Effects of radiation damage on intestinal morphology.
AB  - The current flow of papers on intestinal structure, radiation science, and
      intestinal radiation response is reflected in the contents of this review.
      Multiparameter findings and changes in compartments, cells, or subcellular
      structure all contribute to the overall profile of the response. The well
      recognized changes in proliferation, vessels, and fibrogenesis are accompanied by
      alterations in other compartments, such as neuroendocrine or immune components of
      the intestinal wall. The responses at the molecular level, such as in levels of
      hormones, cytokines, or neurotransmitters, are of fundamental importance. The
      intestine responds to localized radiation, or to changes in other organs that
      influence its structure or function: some structural parameters respond
      differently to different radiation schedules. Apart from radiation conditions,
      factors affecting the outcome include the pathophysiology of the irradiated
      subject and accompanying treatment or intervention. More progress in
      understanding the overall responses is expected in the next few years.

PMID- 11510567
TI  - Nonneuronal cellular prion protein.
AB  - The normal cellular prion protein (PrP(c)) is a membrane sialoglycoprotein of
      unknown function having the unique property of adopting an abnormal tertiary
      conformation. The pathological conformer PrP(sc) would be the agent of
      transmissible spongiform encephalopathies or prion diseases. They include scrapie
      and bovine spongiform encephalopathy in animals and Creutzfeldt-Jakob disease in
      humans. The conversion of PrP(c) into PrP(sc) in the brain governs the clinical
      phenotype of the disease. However, the three-dimensional structure change of
      PrP(c) can also take place outside the central nervous system, in nonneuronal
      cells particularly of lymphoid tissue where the agent replicates. In natural
      infection, PrP(c) in nonneuronal cells of peripheral extracerebral organs may
      play a key role as the receptor required to enable the entry of the infectious
      agent into the host. In the present review we have undertaken a first evaluation
      of compelling data concerning the PrP(c)-expressing cells of nonneuronal origin
      present in cerebral and extracerebral tissues. The analysis of tissue, cellular,
      and subcellular localization of PrP(c) may help us better understand the
      biological function of PrP(c) and provide some information on physiopathological
      processes underlying prion diseases.

PMID- 11510568
TI  - Cellular basis of shoot apical meristem development.
AB  - Shoot apical meristems are composed of proliferating, embryonic type cells, that
      generate tissues and organs throughout the life of the plant. This review covers
      the cell biology of the higher plant shoot apical meristem (SAM). The first
      section describes the molecular basis of plant cell growth and division. The
      genetic mechanisms, that operate in meristem function and the identification of
      several key regulators of meristem behavior are described in the second section,
      and intercellular communication and coordination of cellular behavior in the
      third part. Finally, we discuss some recent results that indicate interaction
      between the cellular regulators, such as the cell cycle control genes and
      developmental regulators.

PMID- 11510569
TI  - Roles of cytoskeletal and junctional plaque proteins in nuclear signaling.
AB  - Cytoplasmic junctional plaque proteins play an important role at intercellular
      junctions. They link transmembrane cell adhesion molecules to components of the
      cytoskeleton, thereby playing an important role in the control of many cellular
      processes. Recent studies on the subcellular distribution of some plaque proteins
      have revealed that a number of these proteins are able to localize in the
      nucleus. This dual location indicates that in addition to promoting adhesive
      interactions, plaque proteins may also play a direct role in nuclear processes,
      and in particular in the transfer of signals from the membrane to the nucleus.
      Therefore, translocation of plaque proteins into the nucleus in response to
      extracellular signals could represent a novel and direct mechanism by which
      signals can be transmitted from the plasma membrane to the nucleus. This could
      allow cells to respond to changing environmental conditions in a rapid and
      efficient way. In addition, conditional sequestration of karyophilic proteins at
      the sites of cell-cell and cell-substratum adhesion may represent a general
      mechanism for the regulation of nucleocytoplasmic transport.

PMID- 11510570
TI  - Thyroidectomy or radioiodine? The value of ultrasonography and cytology in the
      assessment of nodular lesions in Graves' hyperthyroidism.
AB  - Although diffuse toxic goiter is a classical feature of Graves' disease (GD)
      nodular goiters are occasionally found in some patients. The aim of the present
      study was to investigate the ultrasonographic and corresponding cytological
      manifestations in GD patients with nodular lesions to decide on a therapeutic
      strategy. Twenty-seven consecutive GD patients with nodular goiter were included
      in this study (21 women and six men, mean age 41.2 years, range 22-77 years). All
      underwent thyroid ultrasonography and fine-needle aspiration cytology. Of the 27
      patients eight underwent surgical intervention because papillary thyroid
      carcinoma or follicular neoplasm was diagnosed by cytology; five of these were
      shown to have papillary thyroid carcinomas. Ultrasonography revealed the
      malignant nodules to be hypoechogenic, heterogeneous, and with ill-defined
      margins in four of these five thyroid cancers, whereas the remaining sonogram
      showed a cystic change and cauliflower-like tumor formation with
      microcalcification. The volume and maximal diameter of cancerous nodules were
      significantly larger than those of benign nodules. In conclusion our results
      reveal that ultrasonography and fine-needle aspiration cytology are reliable and
      quick methods for diagnosing nodular goiters in GD patients. If thyroid neoplasms
      are found ablative therapy with thyroidectomy is indicated instead of radioactive
      iodine.

PMID- 11510571
TI  - Giant biliary cystadenoma: case report and literature review.
AB  - Biliary cystadenoma is a very rare cystic neoplasm of the liver. This tumor is
      insidiously progressive and usually presents in white females in their fifth
      decade. It has a characteristic appearance on ultrasound, computed tomography,
      and angiography. The exact etiology of these tumors is unknown, but several
      theories have been proposed. Historically these cystic tumors have been treated
      by a variety of techniques including aspiration, fenestration, internal drainage,
      and resection. Previously reported series have confirmed a >90 percent recurrence
      rate with anything less than complete excision. In addition biliary cystadenoma
      is a premalignant lesion and only surgical excision can differentiate it from its
      malignant counterpart, biliary cystadenocarcinoma.

PMID- 11510572
TI  - Paraduodenal hernia: a report of two cases.
AB  - Paraduodenal hernias are uncommon congenital herniations into the mesentery of
      the colon that present as small bowel obstruction. The diagnosis is elusive but
      may be made by CT scan or upper gastrointestinal series. There are three types:
      left, right, and transverse. The repair involves reduction of the hernia and
      closure of the mesenteric defect in accordance with the anatomy of the hernia. We
      present two cases of paraduodenal hernia that are representative of this unusual
      class of internal herniation.

PMID- 11510573
TI  - Hepatic ischemia/reperfusion injury in P-selectin and intercellular adhesion
      molecule-1 double-mutant mice.
AB  - Neutrophil adhesion and recruitment represents one of the early cellular events
      that occur during hepatic ischemia/reperfusion (IR) injury and plays a critical
      role in determining the extent of tissue damage. The adhesion molecules, such as
      selectins and intercellular adhesion molecules (ICAM), are important in mediating
      neutrophil-endothelial cell interactions and neutrophil emigration. The goal of
      this study was to evaluate the role of P-selectin and ICAM-1 in hepatic IR
      injury. Male wild-type and P-selectin/ICAM-1-deficient (P/I null) mice underwent
      90 minutes of partial hepatic ischemia followed by reperfusion at various time
      points (0, 1.5, 3, and 6 hours). Reperfusion caused a time-dependent
      hepatocellular injury in both wild-type and P/I null mice as judged by plasma
      alanine aminotransferase (ALT) levels and liver histopathology examination.
      Although ALT levels were slightly lower in the P/I null mice compared with the
      wild-type mice the differences were not statistically significant. Neutrophil
      infiltration to the ischemic liver was observed in both mouse groups after 6
      hours of reperfusion; however, the infiltration to the midzonal region of the
      ischemic liver was more pronounced in the wild-type group. This study suggests
      that hepatocellular injury induced after hepatic IR was independent of P-selectin
      and ICAM-1 in this model of acute inflammatory tissue injury.

PMID- 11510574
TI  - Postoperative staphylococcal toxic shock syndrome due to pre-existing
      staphylococcal infection: case report and review of the literature.
AB  - Staphylococcal postoperative toxic shock syndrome (PTSS) has been associated with
      a variety of surgical procedures. It is generally believed that the source of
      infection is acquired at or near the time of surgery. PTSS has been specifically
      associated with nasal packing, insertion of hardware, surgical drains, retained
      foreign materials, and breaks in sterile technique. Although PTSS has been
      associated with postoperative abscesses, development of PTSS after surgery of a
      pre-existing source of infection has not been described. We report a case of PTSS
      that developed after vertebral abscess drainage, and we review the literature to
      determine the incidence of PTSS due to preexisting staphylococcal infection.

PMID- 11510575
TI  - Acute necrotizing torsion of the gallbladder.
AB  - Torsion of the gallbladder is an extremely rare cause of acute surgical abdomen.
      Although gallbladder torsion has been reported the diagnosis remains elusive and
      is often missed. A case of necrotizing gallbladder torsion is examined, and the
      literature is reviewed by the authors. History peak incidence and pathophysiology
      are discussed, and possible risk factors are identified. We conclude that torsion
      of the gallbladder is a condition that has minimal clinical findings.

PMID- 11510576
TI  - Outcome of perforated necrotizing enterocolitis in the very low-birth weight
      neonate may be independent of the type of surgical treatment.
AB  - Perforated necrotizing enterocolitis (NEC) in the low-birth weight infant is now
      one of the most common surgical problems encountered in contemporary neonatal
      intensive care units. However, morbidity and mortality from NEC remain high, and
      the optimal surgical management of these infants remains controversial. Currently
      few data exist comparing the factors influencing outcome in very low-birth weight
      infants with perforated NEC treated by either local drainage or exploration. We
      hypothesize that survival of very low-birth weight neonates with perforated NEC
      may be more dependent on clinical status than on treatment modality. We present
      our experience treating a large cohort of infants weighing less than 1000 g with
      perforated NEC. A retrospective cohort study describes our experience with
      perforated NEC in very low-birth weight infants in a Level III neonatal intensive
      care unit. Between January 1991 and May 1998 a total of 70 newbo infants weighing
      less than 1000 g were evaluated and managed for perforated NEC. Comorbid factors
      were identified and calculated for each infant. Primary treatment was either
      local drainage or laparotomy. Statistical analysis was performed by Student's t
      test and multiple logistic regression. A multiple logistic regression model
      examined factors (comorbidities, number of comorbidities, and mode intervention)
      influencing outcome. A Kaplan-Meier survival analysis comparing survival versus
      number of comorbidities was performed. Twenty-two infants with an average weight
      of 679 g were treated by local drainage. Forty-eight infants with an average
      weight of 756 g were treated with exploratory laparotomy. Infants treated by
      local drainage had a higher cumulative number of comorbid factors (5.2+/-0.50 vs
      3.7+/-0.29; P < 0.05) than those managed by operative exploration. Fourteen
      infants (63%) initially undergoing local drainage for perforated NEC survived. Of
      the 48 infants 36 operated on survived (75%). No single factor or combination of
      any comorbid factors was predictive of outcome. The total number of comorbidities
      for each neonate did reach statistical significance (P < 0.05). A greater
      likelihood of death was associated with a higher number of comorbidities.
      Survival with four or fewer comorbidities was 84 per cent, whereas survival with
      greater than six comorbidities was 30 per cent. The mean number of comorbidities
      was greater for drainage than for surgery, and for the same number of
      comorbidities the probability of survival tended to be greater for those treated
      with drainage than for those undergoing surgery. Multiple logistic regression
      analysis identified the total number of comorbidities as affecting outcome rather
      than treatment choice. This suggests therefore that selection of therapeutic
      options for the patient requires evaluating all factors that may impact survival
      rather than applying a single treatment strategy for all patients.

PMID- 11510577
TI  - Blunt innominate artery injury.
AB  - Traumatic injury to the innominate artery is a rare occurrence. A literature
      review reveals that penetrating wounds account for the overwhelming majority of
      these injuries. Fewer than 90 cases of innominate artery injury caused by blunt
      trauma have been documented. Over the past 12 months the trauma service
      successfully treated two patients with blunt injury to the innominate artery.
      Both cases involved high-speed motor vehicle crashes with sudden deceleration.
      Both patients were wearing lap and shoulder restraints and had similar associated
      bruising following the line of the shoulder harness. The first patient presented
      with a wide mediastinum on chest X-ray. Angiography revealed an innominate artery
      injury at the aortic arch. The second patient had a normal chest X-ray. Given the
      extent of soft tissue bruising from the shoulder harness he underwent a magnetic
      resonance angiography, which was suspicious for an innominate artery injury. Arch
      aortography confirmed a disruption of the innominate artery midway between its
      origin and its bifurcation. Both were repaired through a median sternotomy with
      cervical extension as necessary. Given the present technology of safety restraint
      devices this injury may occur with greater frequency. A "shoulder strap sign"
      should prompt a search for more extensive injuries.

PMID- 11510578
TI  - Iatrogenic gallbladder perforation: conservative management by percutaneous
      drainage and cholecystostomy.
AB  - Gallbladder perforation is an uncommon complication of percutaneous liver biopsy.
      Diagnosis is usually made clinically and management has traditionally been by
      cholecystectomy. We report a case of gallbladder perforation secondary to
      percutaneous liver biopsy diagnosed by dimethyl iminodiacetic acid (HIDA) scan
      and managed successfully by percutaneous drainage and cholecystostomy. This case
      illustrates the role of conservative management in selected cases of gallbladder
      perforation.

PMID- 11510579
TI  - Clinical manifestations of gastrointestinal granulocytic sarcoma requiring
      surgical treatment.
AB  - Granulocytic sarcoma is a rare extramedullary soft-tissue tumor of granulocytic
      lineage with an incidence of 3 to 5 per cent in patients with acute myelogenous
      leukemia. The most common sites of involvement are bone, soft tissue, lymph
      nodes, and skin. Here we report three unusual cases of granulocytic sarcoma
      involving the gastrointestinal tract that required surgical intervention.

PMID- 11510580
TI  - Complications of isolated bilateral iliac artery aneurysms.
AB  - Isolated iliac artery aneurysms occur infrequently. They comprise about 2 per
      cent of all abdominal aneurysms. Most patients are symptomatic at the time of
      presentation. The average diameter is 5.7 cm at diagnosis. We report the acutely
      symptomatic presentation of a 76-year-old African-American man with 7- and 9-cm
      bilateral common iliac and a right hypogastic artery aneurysms. Aneurysmorrhaphy
      was complicated by pelvic ischemia. Colonoscopy and arteriography were used
      postoperatively to evaluate the extent of his worsening gluteal ischemia.
      Restoration of pelvic blood flow corrected his gluteal ischemia.

PMID- 11510581
TI  - Pneumothorax after nasoenteral feeding tube placement.
AB  - Nasoenteral tubes are placed routinely for feeding in patients in intensive care
      units and medical-surgical floor settings. Safe placement in the
      stomach/postpyloric location is performed by a wide array of medical personnel.
      We report a patient with placement of a nasoenteral tube into the pleural cavity.

PMID- 11510582
TI  - Local excision of rectal carcinoma.
AB  - The purpose of this study was to identify the recurrence rate, the salvage rate
      after recurrence, and the overall survival after local excision of rectal
      adenocarcinomas. A retrospective medical chart review was performed in 31
      consecutive patients with rectal adenocarcinoma who underwent local excision at
      Roswell Park Cancer Institute from January 1990 through December 1999. After
      excision nine patients were excluded from further analysis because they were
      found to have advanced stage on pathologic examination (T2 primary tumors with
      vascular invasion or T3 tumors). Eight of the nine patients underwent
      abdominoperineal resection as definitive therapy. In the remaining 22 patients
      who underwent transanal excision as definitive surgical therapy there were 13
      patients with T1 tumors and nine patients with T2 tumors. Overall seven patients
      (32%) developed local recurrences after local excision. This included four
      patients with T1 and three patients with T2 primary tumors. All recurrences
      occurred in the seven patients who did not receive adjuvant chemoradiation. All
      patients underwent salvage resection of the recurrence. Four patients who
      underwent salvage resection of the recurrence remain without evidence of disease
      at a median follow-up of 19.5 months. Local excision without adjuvant therapy has
      an unacceptably high rate of local recurrence. Although most patients who recur
      locally are salvaged by radical resection the long-term results after resection
      remain unknown. The use of adjuvant chemoradiation appears to reduce this high
      recurrence rate and may eventually become a standard adjunct to local excision of
      rectal cancer.

PMID- 11510583
TI  - Training background as a factor in the conversion rate of laparoscopic
      cholecystectomy.
AB  - The present study reports findings concerning the impact of the learning
      environment on the conversion rate of laparoscopic cholecystectomy (LC) to open
      cholecystectomy (OC). At Metro-West Medical Center (Framingham, MA) seven
      surgeons performed 866 LCs between 1990 and 1995. Group I consisted of three
      surgeons who learned the procedure as part of their General Surgery Residency
      training, whereas the remaining four surgeons representing Group II learned the
      procedure through private courses. We emphasize the importance of the surgeons'
      training background on the conversion rates, operative times, and length of
      hospitalization for patients undergoing LC. The conversion rates, operative
      times, and complication rates were analyzed with and without a 2-year period of
      adjustment to compensate for the learning curve of early procedures. Operative
      times and conversion rates from LC to OC were lower for cases done by surgeons
      from Group I, even when the learning curve was corrected. The complication rates
      were higher for surgeons in Group II, but this did not reach statistical
      significance. As surgeons from Group II gained more experience their operation
      times and conversion rates decreased. However, there still was a statistically
      significant difference in favor of surgeons who learned the procedure as part of
      a structured curriculum. These data suggest a long-lasting influence of the
      learning environment on the conversion rates and operative times.

PMID- 11510584
TI  - Bouveret's syndrome presenting as upper gastrointestinal hemorrhage without
      hematemesis.
AB  - A 74-year-old woman with a recent diagnosis of peptic ulcer disease diagnosed by
      endoscopy after presentation with an episode of upper gastrointestinal bleeding
      returned 6 1/2 weeks later with a 5-day history of nausea and vomiting without
      associated symptoms. An ultrasound was nondiagnostic except for a large gallstone
      and a poorly visualized gallbladder. Repeat endoscopy revealed a hard mass that
      was presumed to have formed secondarily to an ulcer-induced stricture, and a 6-cm
      filling defect just proximal to the duodenal bulb was seen on a preoperative
      upper gastrointestinal series. At laparotomy the mass was actually a large
      gallstone and two smaller stones, which had eroded into and become impacted in
      the duodenal bulb creating a gastric outlet obstruction. The stones were
      extracted via a duodenotomy, and the remaining portion of the gallbladder was
      removed with repair of the cholecystoduodenal fistula. The patient was discharged
      home after an uncomplicated postoperative course. Gastric outlet obstruction by a
      duodenal gallstone is a condition known as Bouveret's syndrome, which is a rare
      complication of gallstone disease. Upper gastrointestinal hemorrhage is an
      especially rare form of presentation.

PMID- 11510585
TI  - Simultaneous placement of long-term central venous catheters and surgical
      debridement for treatment of osteomyelitis.
AB  - Nonhealing wounds with underlying osteomyelitis require surgical debridement and
      a course of intravenous antibiotics usually via long-term venous catheter. Fear
      of catheter infection resulting from bacteremia or direct cross-contamination has
      traditionally led to staged procedures. A protocol for simultaneous placement of
      a long-term central venous catheter (Hickman) for antibiotic therapy and surgical
      debridement of chronic wounds with osteomyelitis does not result in elevated
      catheter-related infections. We conducted a prospective consecutive trial at a
      community-based tertiary-care training hospital. From October 1995 through June
      1997 100 consecutive patients received 105 central venous catheters and surgical
      debridement for treatment of chronic wounds with underlying osteomyelitis at the
      same operative setting. Four catheters required removal because of infectious
      complications. There was no correlation between the bacteria cultured from the
      central venous line or blood cultures and the wound cultures. Combining placement
      of long-term central venous catheters and surgical debridement of chronic wounds
      with osteomyelitis at one operative setting results in an acceptably low catheter
      infection rate.

PMID- 11510586
TI  - Nonoperative management of solid abdominal organ injuries from blunt trauma:
      impact of neurologic impairment.
AB  - The role of nonoperative management of solid abdominal organ injury from blunt
      trauma in neurologically impaired patients has been questioned. A statewide
      trauma registry was reviewed from January 1993 through December 1995 for all
      adult (age >12 years) patients with blunt trauma and an abdominal solid organ
      injury (kidney, liver, or spleen) of Abbreviated Injury Scale score > or =2.
      Patients with initial hypotension (systolic blood pressure <90 mm Hg) were
      excluded. Patients were stratified by Glasgow Coma Score (GCS) into normal (GCS
      15), mild to moderate (GCS 8-14), and severe (GCS < or =7) impairment groups.
      Management was either operative or nonoperative; failure of nonoperative
      management was defined as requiring laparotomy for intraabdominal injury more
      than 24 hours after admission. In the 3-year period 2327 patients sustained solid
      viscus injuries; 1561 of these patients were managed nonoperatively (66 per
      cent). The nonoperative approach was initiated less frequently in those patients
      with greater impairment in mental status: GCS 15, 71 per cent; GCS 8 to 14, 62
      per cent; and GCS < or =7, 50 per cent. Mortality, hospital length of stay, and
      intensive care unit days were greater in operatively managed GCS 15 and 8 to 14
      groups but were not different on the basis of management in the GCS < or =7
      group. Failure of nonoperative management occurred in 94 patients (6%). There was
      no difference in the nonoperative failure rate between patients with normal
      mental status and those with mild to moderate or severe head injuries.
      Nonoperative management of neurologically impaired hemodynamically stable
      patients with blunt injuries of liver, spleen, or kidney is commonly practiced
      and is successful in more than 90 per cent of cases. No differences were noted in
      the rates of delayed laparotomy or survival between normal, mild to moderately
      head-injured, and severely head-injured patients.

PMID- 11510587
TI  - Sequential changes in mucosal immunity after hemorrhagic shock.
AB  - Immunoinflammatory responses after shock and major trauma are characterized by an
      early hyperinflammatory response and later by compensatory anti-inflammatory host
      mediator production. This late phase is associated with depressed immune function
      that has been causally linked with post-traumatic infectious complications and
      late organ failure. Gut barrier failure is noted in this setting and may be an
      important source of nosocomial infections and organ failure. Secretory
      immunoglobulin A (sIgA) is the predominant immunoglobin at mucosal surfaces and
      is difficult to quantify in luminal secretions. Attempts to normalize sIgA
      concentrations may not be accurate and/or may not be applicable in vivo. A method
      using mucosal immunization with cholera toxin (ChT) to normalize gut sIgA levels
      was used to assess serial changes in sIgA after hemorrhagic shock (HS) in
      rodents. Total and anti-ChT sIgA levels were highly variable in both HS and sham
      animals. However, when normalized using the specific anti-ChT/total sIgA ratio,
      differences were clearly evident. This ratio was depressed between 3 and 10 days
      post-HS. The specific anti-ChT/total sIgA ratio is a reliable index of secretory
      antibody at gut luminal surfaces. Impaired mucosal immune function occurred in a
      time frame consistent with development of late nosocomial infections. This may be
      important mechanistically in the development of these infectious complications.

PMID- 11510588
TI  - K-ras mutational analysis of polyclonal colorectal cancers identifies uniclonal
      circulating tumor cells.
AB  - The clonal development of colorectal carcinoma resulting from specific mutations
      in certain oncogenes and/or tumor suppressor genes is a well-accepted model. It
      is increasingly recognized that a majority of colorectal cancers are polyclonal
      on the basis of molecular analysis that demonstrates cells with different
      mutations within a given oncogene or tumor suppressor gene in the same tumor.
      This polyclonal pattern may occur as a result of either clonal convergence or
      divergence during the many steps of oncogenesis. Further complicating this
      picture is the fact that metastatic lesions may arise from only one of the clonal
      populations within a tumor and thereby present only a partial molecular make-up
      of the whole tumor. There are few data available that define clonal selection or
      specificity of circulating tumor cells in patients undergoing curative resection
      of colorectal carcinoma. The purpose of this paper is to describe the clonal
      distribution of circulating tumor cells in four patients with multiple K-ras
      mutations present in the primary lesion. Patients were selected who were known to
      have polyclonal primary colorectal cancers resected for cure. All patients had
      multiple mutations present in exon one, codon 12 and/or 13, of the K-ras gene.
      Blood samples were drawn immediately before surgery and at 2-week to 6-month
      intervals postoperatively. Epithelial cells were isolated from peripheral blood
      mononuclear cells using Dynal Immunobeads coated with antiepithelial antibodies.
      DNA was extracted from these cells and analyzed for all K-ras mutations present
      in codons 12 and 13 of the patient's primary tumor using allele-specific
      polymerase chain reaction followed by Microwell Array Diagonal Gel
      Electrophoresis. Circulating tumor cells were identified in all four patients.
      However, in each case of positive circulating cells the only mutation identified
      was an aspartic acid mutation at codon 13. Once positive the circulating tumor
      cells persisted in subsequent multiple blood samples. These results provide
      further strength for the theory of polyclonal progression in primary colorectal
      cancers, although there may be specific mutational patterns that confer the
      ability to metastasize. The significance of this persistence of the glycine-to
      aspartic acid mutation at codon 13 remains to be defined given that none of these
      patients has clinical evidence of recurrent cancer at the time of this report.

PMID- 11510589
TI  - A simplified open gastrostomy under local anesthesia.
AB  - Revision of the standard gastrostomy is often necessary in patients with
      neuromuscular disorders. These patients pose many anesthetic risks that
      frequently preclude the use of general anesthesia, intravenous sedation, or
      endoscopy. Modification of the Stamm gastrostomy enables it to be performed
      comfortably and readily under local anesthesia. The modification proposed passes
      the gastrostomy tube through the omentum en route to the abdominal wall. This
      ensures a seal to the surgical site, eliminates the need for tacking sutures, and
      allows for a smaller midline incision. These factors greatly reduce the
      discomfort of the procedure allowing it to be easily accomplished under local
      anesthesia. This technique of open gastrostomy under local anesthesia has been
      used in more than 35 patients over the past 10 years with no documented leaks.

PMID- 11510590
TI  - The critical technical aspects of laparoscopic repair of ventral and incisional
      hernias.
AB  - Several authors have revealed the utility of the laparoscopic approach to hernia
      defects that involve the ventral surface of the abdominal wall. The results of
      these series have been favorable. These authors all have recognized that
      appropriate sizing and fixation are important components of this operation. The
      pitfalls of the laparoscopic repair of incisional hernias are few but are
      significant. The most important technical considerations are dissection of all
      adhesions and clear identification of the fascial defect, prosthesis overlap of 3
      cm in all directions, and fixation by through and through sutures and spiral
      tacks. The attention to these factors will diminish the risk of the immediate and
      long-term complications of the repair of these fascial defects.

PMID- 11510591
TI  - Judicial lithiasis.

PMID- 11510592
TI  - Re: Is there a role for interval appendectomy in the management of acute
      appendicitis?

PMID- 11510593
TI  - Classification of chronic venous insufficiency: a review.
AB  - Chronic venous insufficiency (CVI) is a very variable and complex entity that has
      stimulated different attempts at classification. Several proposals have been made
      in recent years, based on objective and anatomical criteria, most of them
      incomplete and unsatisfactory. Finally the CEAP classification was presented in
      1994. This certainly is the most nearly complete classification, since it takes
      into consideration not only the main aspects of CVI: Clinical, Etiological,
      Anatomical, and Pathophysiological, but also the degrees of severity, reported in
      the form of scores. It is now accepted internationally although it still has some
      flaws (such as the absence of the corona phlebectactica sign) and inaccuracies
      (above all in the clinical part and the scoring). Recently, some members of the
      Promoting Committee proposed a substantial modification of the part on scores,
      coming closest to the clinical reality, instrumental diagnosis, and current
      therapies. The characteristics of CEAP enable us to affirm that this represents
      the most original and useful classification, not only for clinical studies, but
      also in the assessment of therapeutic results and in patient follow-up. Like all
      classifications, CEAP also needs to be validated by means of clinical studies in
      order to demonstrate its applicability. For this purpose, a European Working
      Group was set up in 1997. The first interesting results of 872 dossiers collected
      by means of a computerized program (European Phlebological File) were presented
      at several international congresses and concentrated on the consistency and
      reproducibility of the clinical part of the CEAP classification in different
      clinical settings.

PMID- 11510594
TI  - New advances in the understanding of the pathophysiology of chronic venous
      insufficiency.
AB  - Chronic venous insufficiency (CVI) is inseparably linked to elevated venous
      pressure and is accompanied by vascular, dermal, and subcutaneous tissue damage
      and restructuring. Abundant evidence exists both in humans and in experimental
      models to suggest that the tissue damage may be initiated by generation of an
      inflammatory reaction. Inflammatory indicators include elevation of endothelial
      permeability; attachment of circulating leukocytes to the endothelium;
      infiltration of monocytes, lymphocytes, and mast cells into the connective
      tissue; and development of fibrotic tissue infiltrates and several molecular
      markers, such as growth factor or membrane adhesion molecule generation.
      Indicators of an inflammatory reaction are already detectable at early stages of
      CVI and may be involved in the development of primary venous valve dysfunction.
      One of the important questions is to identify trigger mechanisms for the
      inflammatory reaction in CVI. Current evidence suggests that, among several
      possible mechanisms (hypoxia, humoral stimulation), a shift in fluid shear stress
      from normal physiological levels and endothelial distension under the influence
      of elevated venous pressure may serve as trigger mechanisms for inflammation.

PMID- 11510595
TI  - Update on chronic-venous-insufficiency-induced inflammatory processes.
AB  - The causes of venous ulceration remain unclear. Twentieth-century hypotheses
      concentrated on the possibility that this problem was caused by failure of oxygen
      delivery to the skin. However, it has been difficult to substantiate these
      predictions in practice. Although the presence of tissue hypoxia has been
      suggested by studies in which transcutaneous oxygen tension has been assessed
      with transducers heated to unphysiological temperatures, when oxygen measurements
      are made at room temperature there is little evidence of tissue hypoxia. This has
      led to the assessment of alternative mechanisms of ulcer development. There has
      been considerable interest in recent years in the inflammatory processes that
      surround venous ulceration. A complex sequence of events appears to surround the
      development of leg ulceration. Increased leukocyte activation has been shown in
      patients with venous disease as well as increased expression of soluble
      endothelial adhesion molecules. Histologic studies of the skin in patients with
      chronic venous disease show a perivascular infiltration of the capillaries of the
      papillary plexus (the most superficial part of the dermis) with monocytes,
      macrophages, and connective tissue proteins including fibrin. Fibrosis of the
      skin and subcutaneous tissues may be initiated by increased gene expression and
      production of transforming growth factor-beta1. Vascular endothelial growth
      factor may be involved in the capillary proliferation that has been reported in
      the skin by a number of authors. Increased expression of several tissue
      metalloproteinases has been reported both in liposclerotic skin and periulcer
      skin. The tissue inhibitors of metalloproteinases are also increased and the net
      result is unclear. Treatment of venous disease using micronized purified
      flavonoid fraction moderates some of the inflammatory markers, including
      leukocyte ligand expression and endothelial adhesion molecule shedding. These
      compounds have also been shown to reduce leukocyte-endothelial adhesion in animal
      models of ischemia-reperfusion injury. Many inflammatory processes have now been
      shown to be involved in the development of the skin changes in patients with
      chronic venous disease. However, the precise sequence of events that leads to leg
      ulceration is still unclear. Pharmacologic treatments aimed at moderating some of
      these inflammatory processes are now under investigation as potential ways of
      treating patients with the more advanced stages of venous disease.

PMID- 11510596
TI  - Therapeutic approach to chronic venous insufficiency and its complications: place
      of Daflon 500 mg.
AB  - Early manifestations of chronic venous insufficiency (CVI) are edema,
      hyperpigmentation, and lipodermatosclerosis. Late complications are cutaneous
      ulceration and delayed healing. The specific hallmarks of this inflammation
      include CD68-positive infiltration into the dermal tissue, monocytes, and
      lymphocytes and enhanced endothelial permeability. This may lead to "fibrin cuff"
      formation. In addition, membrane adhesion molecules are present and cytokine
      expression is seen. In one experimental model of mesenteric venous hypertension,
      the inflammatory process was detected in its earliest stages. This was evident in
      the form of neutrophilic leukocyte adhesion to venular endothelium as well as
      migration of cells across the endothelium and basement membrane into the
      interstitial space. Simultaneously, parenchymal cell death was detected. This
      suggests that the mechanism that triggers the inflammatory reaction is venous
      hypertension. This may cause venous distension and a shift in fluid shear stress.
      Our observations suggest that patients with venous insufficiency demonstrate
      circulatory humoral stimulators for leukocyte activation. Otherwise, there is
      evidence that the inflammatory reaction is limited to the region of the venous
      ulceration or at least to the skin areas with severe microangiopathy. It may be
      that activated leukocytes traverse perivascular cuffs and release active
      transforming growth factor-beta1 (TGF-beta1) which has been found to be elevated
      exclusively in areas of clinically active CVI. Surgical intervention markedly
      decreases the number of dysfunctional vein segments and allows pharmacologic
      agents to protect normal structures from continuing damage. Daflon 500 mg, the
      purified micronized flavonoid fraction containing 90% diosmin and 10% hesperidin,
      acts favorably in venous ulcer treatment by inhibiting the synthesis of
      prostaglandins and free radicals. It decreases bradykinin-induced microvascular
      leakage and may act favorably to inhibit leukocyte activation, trapping, and
      migration. Clinically, edema is reduced, ulcer healing is accelerated, and
      leukocyte trapping diminished. The action of micronized purified flavonoid
      fraction is beginning to be better understood, and as further knowledge is
      gained, better pharmacologic control of CVI is a tantalizing promise.

PMID- 11510597
TI  - Clinical benefits of Daflon 500 mg in the most severe stages of chronic venous
      insufficiency.
AB  - Chronic venous insufficiency (CVI) affects a large number of people in Western
      countries, and is responsible for considerable inconvenience, discomfort,
      suffering, and costs. Micronized purified flavonoid fraction (MPFF, 450 mg
      diosmin plus 50 mg hesperidin-Daflon 500 mg) is a potent venotropic drug used in
      the treatment of venous insufficiency. Pharmacological and clinical studies
      demonstrated the comprehensive mode of action of Daflon 500 mg: it increases
      venous tone, it improves lymph drainage, and it protects the microcirculation.
      Clinical international, prospective, multicenter, randomized, controlled studies
      versus placebo studies documenting the effects of Daflon 500 mg in CVI at
      advanced stages with edema, skin changes, and venous leg ulcer are reviewed. In
      edema, one of the most frequent complaints of patients, Daflon 500 mg brings
      about a significant reduction in leg circumference, thanks to its capacity to
      inhibit inflammatory reactions and to decrease capillary hyperpermeability. The
      rationale for the use of Daflon 500 mg for treatment of skin disorders and venous
      leg ulcer is its action on the microcirculation-damaging processes. Regarding
      skin changes, Daflon 500 mg has been shown to improve venous trophic disorders,
      like gravitational (stasis) dermatitis, and dermatofibrosclerosis. In venous leg
      ulcer, Daflon 500 mg's clinical efficacy has been demonstrated in addition to
      standard treatment or versus standard treatment alone. Daflon 500 mg, thanks to
      its comprehensive mode of action on the veins, lymphatics, and microcirculation,
      is the method of choice not only in the early stages of CVI treatment, but also
      in the severe stages of this condition, in combination with compression
      treatment, sclerotherapy, and surgery if appropriate.

PMID- 11510598
TI  - Prevalence and risk factors of chronic venous insufficiency.
AB  - Venous disease in the legs occurs very commonly in the general population in
      Western countries. Around one third of women have trunk varices. A lower
      prevalence has been observed in men but some recent surveys have suggested that
      the occurrence in men may be comparable to that in women. The prevalence
      increases with age but the incidence of new cases appears to be constant
      throughout adult life. Open venous ulcers occur in about 0.3% of the adult
      population and a history of open or healed ulceration occurs in around 1%. The
      etiology of chronic venous disease in the legs is unknown. A genetic
      predisposition may be present but evidence for this and for a mode of inheritance
      is lacking. There is some suggestion that prolonged standing may be a risk factor
      but studies are open to considerable bias. In women, obesity and previous
      pregnancy has been associated with the presence of varicose veins but the
      evidence is inconsistent. There have been few well-conducted studies examining
      diet and bowel habit as a risk factor. The risk of ulceration is related to the
      severity of varicosities and venous insufficiency, and is increased following
      deep vein thrombosis. Much further research is required to investigate the cause
      of this common condition in the general population.

PMID- 11510599
TI  - Minimally invasive open thyroidectomy.
AB  - We recently developed a new surgical technique for carrying out thyroidectomy, to
      minimize tissue trauma by obviating unnecessary neck exploration. This report
      describes our technique of performing minimally invasive open thyroidectomy and
      compares the results with those of conventional thyroidectomy. Minimally invasive
      open thyroidectomy was performed by making a small skin incision, 3.0-4.5cm long,
      and approaching the thyroid directly via a transverse division of the strap
      muscles without raising skin flaps. The outcomes of 466 patients who underwent a
      minimally invasive open thyroidectomy were retrospectively compared with those of
      437 patients who underwent conventional thyroidectomy for various types of
      thyroid nodules. There was no significant difference in the extent of surgery
      between the group of patients who underwent minimally invasive thyroidectomy and
      the group of patients who underwent conventional thyroidectomy. However, the
      length of the skin incision, at 3.7 +/- 0.7 vs 9.6 +/- 3.3 cm, respectively,
      operative time, at 57.6 +/- 11.7 vs 85.2 +/- 32.3 min, respectively, blood loss,
      at 18.4 +/- 15.3 vs 43.1 +/- 21.8 ml, respectively, and hospital stay, at 1.6 +/-
      0.5 vs 4.3 +/- 1.6 days, respectively, were significantly reduced in the
      minimally invasive open thyroidectomy group (P < 0.05). Moreover, the number of
      patients who required postoperative analgesia was significantly less in the
      minimally invasive open thyroidectomy group. These results show that minimally
      invasive open thyroidectomy provides surgeons with a clear operative field, and
      that it has proven to be simple, safe, and practical for selected patients.

PMID- 11510600
TI  - Multicentric occurrence of esophageal cancer after gastrectomy: a preliminary
      report.
AB  - The effect of gastrectomy on the subsequent development of esophageal cancer was
      investigated, focusing on its multicentric occurrence. We retrospectively
      evaluated 28 patients who underwent subtotal esophagectomy for intrathoracic
      esophageal cancer between 1985 and 1999. They were divided into two groups
      according to whether or not they had previously undergone a gastrectomy: group 1,
      comprising 7 patients who had undergone gastrectomy and group 2, comprising 21
      patients who had not. Clinical profiles of the patients were obtained from the
      medical records and the whole resected esophagus was histopathologically
      examined. The interval between gastrectomy and esophagectomy in group 1 was
      significantly shorter in the patients who had undergone gastrectomy for gastric
      cancer than in those who had undergone gastrectomy for a peptic ulcer, and also
      in the patients for whom anastomosis had been performed by Billroth I compared
      with Billroth II. The patients in group 1 were significantly younger than those
      in group 2. The multiple occurrence of esophageal cancer was found in 4 of 5
      patients (80%) in group 1, and in 2 of 18 patients (11%) in group 2, with
      significantly higher frequency being seen in group 1. More than two coexisting
      cancer lesions apart from the primary tumor were detected in all four patients.
      Histological examination of all the coexisting cancer lesions showed well
      differentiated squamous cell carcinoma confined within the superficial mucosal
      layer. No significant differences were noted in the location of the coexisting
      lesions between the oral and anal side of the primary tumors. Squamous dysplasia
      was randomly observed, especially around the cancer lesions. These findings
      suggest that gastrectomy precipitated subsequent chronic gastroesophageal reflux
      which in turn induced the development of squamous dysplasia and carcinoma at
      multiple locations in the esophagus.

PMID- 11510601
TI  - The management of appendiceal mass in children: is interval appendectomy
      necessary?
AB  - In this study we aimed to show that performing interval appendectomy is
      unnecessary in the management of appendiceal mass in children. Between 1990 and
      1996, 866 patients were treated for appendicitis. Abdominal ultrasonography (USG)
      was performed in patients who were admitted with abdominal pain, vomiting, and
      fever accompanying a mass in the right lower quadrant. Seventeen patients (12
      boys and 5 girls, with a mean age of 9.5 years) with a mass in the appendiceal
      lodge and no abscess formation were treated conservatively. Appendectomy was
      performed on any patients with perforated or unperforated appendicitis who had an
      appendiceal abscess with a mass in the right iliac fossa. Three-agent antibiotic
      therapy was administered for at least 1 week. These patients were discharged
      after a mean hospital time of 9.7 days if regression of the mass was seen
      ultrasonographically. They were followed up for 1-60 months by physical
      examination and USG, and 11 of the 17 also underwent barium enema. USG
      demonstrated disappearance of the mass and barium enema showed a normal appendix
      in 10 of the 11 patients. No recurrent appendicitis was detected during follow-up
      for 1-7 years. This study shows that appendiceal masses that are perforated, but
      localized with no fluid content revealed by USG, can be treated conservatively
      even if they are detected late.

PMID- 11510602
TI  - Colostomy closure using local anesthesia.
AB  - The feasibility of performing colostomy closures using local anesthesia was
      evaluated. The subjects comprised 14 patients: 2 with colostomies involving a
      mucous fistula and 12 with loop colostomies. Patients who had colostomies with
      mucous fistulas separated by 10cm or more were excluded from this study. All
      patients were graded as ASA 1 (according to the American Society of
      Anesthesiologists). The bowel was evaluated by colonoscopy in 6 patients and by
      barium enema in 8 patients. Bowel preparation was performed with Colayte and all
      patients were given prophylactic antibiotics. Closure of the colostomy was
      extraperitoneal and the time taken to perform the operation ranged from 40 to
      120min. Tolerance was regarded as excellent in 9 patients, good in 3, and average
      in 2. There were 3 anastomotic leaks that resolved without further surgical
      treatment, 2 wound infections, and 1 bowel obstruction that was successfully
      treated with medication. Patients were discharged 2-22 days postoperatively,
      after a mean period of 9 days. Local anesthesia offers a safe and effective
      alternative to general or regional anesthesia for surgical closure of
      colostomies.

PMID- 11510603
TI  - Cause of death in renal transplant patients: a comparison between azathioprine
      and ciclosporin.
AB  - The results of renal transplantation have improved due to advances in
      immunosuppression techniques of preservation, and pre- and postoperative
      treatments; however, both morbidity and mortality remain serious problems. To
      decrease the morbidity and mortality rates we analyzed the causes of death after
      renal transplantation in our hospital. Between 1972 and 1999, we performed 364
      renal transplantations, 257 of which were living-related and 107, cadaveric.
      There were 178 patients given azathioprine and 186 given ciclosporin. The
      survival rate of the patients on ciclosporin therapy was much better than that of
      those on azathioprine therapy. Of the total 364 renal transplant patients, 59
      (16.2%) died, and 28 (47.5%) of these 59 deaths occurred within 1 year after
      renal transplantation. The causes of death were infection in 19 (32.2%) patients,
      gastrointestinal diseases in 16 (27.1%), cardiovascular diseases in 11 (18.6%),
      cerebrovascular diseases in 6 (10.2%), suicide in 3 (5.1%), and other causes in 4
      (6.8%). These findings reinforce that early diagnosis and treatment are essential
      to decrease the morbidity and mortality rates assoiated with renal
      transplantation.

PMID- 11510604
TI  - Three-dimensional simulation of the Blalock-Taussig shunt using computational
      fluid dynamics.
AB  - To examine blood flow after the placement of a Blalock-Taussig shunt, three
      complex T-figure models were developed according to shunt size and the degree of
      pulmonary artery hypoplasia. With the use of computational fluid dynamics, the
      net energy loss and wall shear stress were calculated under pulsatile conditions.
      We calculated that the 5-mm shunt carried the least energy loss, but the most
      wall shear stress. In this simulation, the 5-mm shunt was thought to be superior
      to the 4-mm and 3-mm shunts in terms of energy loss and smooth flow, but it
      produced high wall shear stress.

PMID- 11510605
TI  - Evaluation of the acetaminophen absorption test for early detection of orthotopic
      small bowel transplant rejection.
AB  - We evaluated the efficiency of the acetaminophen (AC) absorption test as a marker
      of graft rejection in orthotopic small bowel transplantation (SBTX) in rats.
      Brown Norway (BN) rats were used as donors and Lewis (LEW) rats as recipients.
      Orthotopic allogenic SBTX was accomplished using a cuff technique for vessel
      anastomosis. Animals were divided into: group A (n = 9), untreated; group B (n =
      15), extended small bowel resection; group C (n = 12), syngeneic SBTX without
      immunosuppressants; group D (n = 15), allogenic SBTX with tacrolimus (0.1 mg/kg
      per day); group E (n = 15), allogenic SBTX with tacrolimus (0.5mg/kg per day).
      Serum AC was measured 15 min following the instillation of 0.15 g/kg AC into the
      stomach on postoperative days (POD) 1, 3, and 7. Grafts were examined
      histologically. The group D grafts showed progressive acute rejection
      histologically, from normal on POD 1, to moderate on POD 3, and severe on POD 7.
      Serum AC in group D decreased significantly from 53.1 +/- 3.9 microg/ml on POD 1,
      to 35.0 +/- 12.0 microg/ml on POD 3, and 10.9 +/- 5.6 microg/ml on POD 7. No
      remarkable change was observed in the other groups. Serum AC correlated well with
      histological changes in rats subjected to SBTX, resulting in acute rejection. The
      AC absorption test could be useful for detection of progressive graft rejection
      in clinical SBTX.

PMID- 11510606
TI  - Intralobar pulmonary sequestration supplied by multiple anomalous arteries:
      report of a case.
AB  - Pulmonary sequestration is abnormal pulmonary tissue that has separated from the
      normal pulmonary parenchyma, is not connected to the tracheobronchial tree, and
      is supplied by a systemic artery. We describe herein a case of intralobar
      pulmonary sequestration found in a 66-year-old man who was admitted to our
      hospital with hemoptysis, coughing, and fever. Angiography showed that the
      branches of the 11th left intercostal artery and a bronchial artery had formed a
      hypervascular area in the lower part of the left lung. Bronchial artery
      embolization and subsequent embolization of the left 11th intercostal artery were
      performed in an attempt to control the recurrent hemoptysis. These treatments
      were unsuccessful, and he was transferred to our department of surgery after
      coughing up about 400 ml of fresh blood. A left lower lobectomy was performed.
      The resected lung contained a large feeding artery, some acute and partly
      organizing inflammatory lesions within collapsed lung parenchyma, and massive
      intra-alveolar hemorrhage in the peripheral area. The patient had an uneventful
      recovery and was discharged 22 days after his operation.

PMID- 11510607
TI  - Pulmonary blastoma in a child: report of a case.
AB  - We describe herein the case of a 2-year-old girl found to have a pulmonary
      blastoma (PB). The child was admitted to our hospital with the chief complaints
      of coughing and left-sided chest pain. On admission, a chest X-ray revealed a
      large mass in the left lung, which measured 10cm in diameter. Computed tomography
      and magnetic resonance imaging showed a marginally and heterogeneously enhanced
      tumor filling the left hemithorax. Pathologic findings of the fine-needle
      aspiration were suggestive of neuroblastoma. Subsequently, a left pneumonectomy
      with lymph node dissection was performed and histopathological examination
      confirmed that the tumor was a PB (type III). After the definitive diagnosis was
      made the patient received combination chemotherapy, and no evidence of recurrence
      has been seen in the 5 months since surgery.

PMID- 11510608
TI  - Transdiaphragmatic intercostal hernia following a penetrating thoracoabdominal
      injury: report of a case.
AB  - Intercostal hernias with abdominal viscera have rarely been reported following
      penetrating accidental or surgical trauma. We report herein a case of a traumatic
      rupture of the left hemidiaphragm, presenting as an intercostal hernia 2 years
      after a penetrating thoracoabdominal injury. The diaphragmatic rupture had been
      initially very small and could not be detected in the serial chest films and
      abdominal computed tomographic scans. The injury was also missed during an
      exploratory lateral thoracotomy. The patient was admitted with the chief
      complaint of a painful and gradually enlarging left-sided chest wall bulge of 8
      months' duration. Surgery via an anterolateral thoracotomy along the axis of the
      intercostal hernia was performed, and the omentum and splenic flexura of the
      colon were reduced.

PMID- 11510609
TI  - Spontaneous nontraumatic rupture of the thoracic aorta: report of a case.
AB  - Spontaneous nontraumatic rupture of the thoracic aorta is a very rare, life
      threatening condition for which emergency diagnostic and therapeutic measures are
      indicated. The patient reported herein suffered a spontaneous rupture of the
      thoracic descending aorta through an atheromatous plaque without aneurysmal
      formation. When acute intrapericardial, mediastinal, or intrapleural bleeding
      develops without any evidence of aortic aneurysm or dissection, the possibility
      of spontaneous rupture of the thoracic aorta should be considered in the
      differential diagnosis, and appropriate emergency surgery may be life-saving.

PMID- 11510610
TI  - Gastrointestinal stromal tumor of the lesser omentum: report of a case.
AB  - We describe herein an extremely unusual case of a gastrointestinal stromal tumor
      (GIST) of the lesser omentum. A 45-year-old man was admitted to our hospital with
      an intra-abdominal mass that was subsequently misdiagnosed as a submucosal tumor
      of the stomach. The tumor arose from the lesser omentum and was removed without
      difficulty. Histologically, the tumor was composed of spindle-shaped cells with
      an interlacing bundle pattern, and immunohistochemical examination showed that it
      was positive for myeloid stem cell antigen (CD34), but negative for HHF35 and S
      100 protein. These findings were consistent with a GIST lacking myogenic features
      and neural attributes. The patient had an uneventful postoperative course, and
      was free of recurrence when last seen 11 months after his operation.

PMID- 11510611
TI  - Posttraumatic pseudocyst of the greater omentum: report of a case.
AB  - Posttraumatic intra-abdominal cysts generally develop in relation to solid
      abdominal organs and most originate as a result of the organization of fluid or
      blood collection after trauma. They lack true endothelial lining and are hence
      called "pseudocysts." We report herein the rare case of a traumatic pseudocyst of
      the greater omentum in a 6-year-old child who was successfully treated by
      laparotomy and excision of the cyst.

PMID- 11510612
TI  - Gastrointestinal stromal tumor of the duodenal ampulla: report of a case.
AB  - We report herein the case of a 77-year-old woman with a gastrointestinal stromal
      tumor (GIST) of the duodenal ampulla. The tumor, which was removed by
      pancreatoduodenectomy due to its malignant potential, showed expansive growth in
      the muscular coat of the duodenal ampulla. Histologically, the tumor cells were
      spindle-shaped or round, and exhibited fascicular or storiform growth pattern
      with frequent mitotic figures. The immunohistochemical and ultrastructural
      results suggested that the tumor may have originated from the interstitial cells
      of Cajal in the muscular coat of the duodenal ampulla. To our knowledge, this is
      the first case of malignant GIST of the duodenal ampulla to be reported in Japan.

PMID- 11510613
TI  - Primary malignant fibrous histiocytoma of the ileum: report of a case.
AB  - We report herein a case of primary malignant fibrous histiocytoma (MFH) of the
      ileum. A 71-year-old Japanese man was admitted to our hospital with symptoms of
      abdominal pain and anorexia. Computed tomography, magnetic resonance imaging, a
      follow-through study of the small intestine, and angiography all demonstrated a
      tumor of the ileum suggestive of a primary malignancy. A partial resection of the
      ileum was performed. It was histopathologically and immunohistochemically
      diagnosed to be a storiform-type primary MFH of the ileum with peritoneal
      dissemination. There have been a total of 25 cases of primary small bowel MFH
      documented in the Japanese or Western literature including our case. The
      malignant potential of such tumors is high, and the prognosis tends to be very
      poor. Unfortunately, we could not conclude whether the poor outcome was due to a
      delayed diagnosis or instead to its biological malignant behavior, since the
      number of such reported cases is still too small to make any definitive
      conclusions.

PMID- 11510614
TI  - Giant congenital solitary cyst of the liver: report of a case.
AB  - Giant solitary nonparasitic cysts of the liver are rarely encountered in
      children, and establishing a preoperative diagnosis is usually difficult,
      especially when the cyst occupies the entire abdomen. We report herein the case
      of an 8-year-old girl found to have a giant congenital solitary cyst of the liver
      masquerading as an ovarian cyst.

PMID- 11510615
TI  - Hepatocellular carcinoma with a sarcomatous appearance: report of a case.
AB  - A 59-year-old man was admitted with general fatigue, an epigastric mass, and
      remittent fever. Radiological examinations disclosed a huge solid-to-cystic mass
      in the right lobe of the liver, and the mass severely compressed the right
      diaphragm, the inferior vena cava, and the right atrium. In addition, the patient
      suffered from chronic hepatitis; however, the serum alpha-fetoprotein,
      carcinoembryonic antigen, and PIVKA II levels were all within the normal ranges.
      The serum C-reactive protein level was 7.71mg/dl. With a clinical diagnosis of a
      malignant hepatic tumor invading the right diaphragm, surgery was performed. The
      tumor originated from segments IV and VII of the liver, was well defined, and
      grew extrahepatically. The tumor was resected using an ultrasonic cavitational
      aspirator together with the infiltrated right diaphragm. The resected tumor
      measured 23 x 13 x 23cm in size and weighed 3,700 g. Histologically, the tumor
      was found to consist of hepatocellular carcinomatous component and sarcomatous
      component. In the sarcomatous component, spindle-shaped cells which were positive
      for the immunohistochemical localization of vimentin, alpha-smooth muscle actin,
      and keratin were identified. The postoperative course was uneventful. The value
      of the serum C-reactive protein returned to within the normal range, and the
      patient became afebrile. The patient received a postoperative combination
      chemotherapy (etoposide, epirubicin, and cisplatin), and remains well with no
      signs of recurrence 12 months after the operation.

PMID- 11510616
TI  - New technique of laparoscopic-assisted excision of a cholecystocolic fistula:
      report of a case.
AB  - Cholecystocolic fistula is a rare complication of gallstone disease that is most
      commonly diagnosed at the time of surgery. It is generally considered to be a
      contraindication to laparoscopic cholecystectomy because of the difficulties
      involved in its management intraoperatively. Laparoscopic stapling or suturing
      techniques have been reported as feasible and safe methods for repairing such
      fistulas; however, these procedures are not always able to be performed due to
      technical difficulties. We exteriorized a cholecystocolic fistula through an
      umbilical incision, whereby it was repaired safely and easily. This report
      describes our new technique for managing a cholecystocolic fistula found
      incidentally during a laparoscopic cholecystectomy.

PMID- 11510617
TI  - Huge cystic lymphangioma of the pancreas: report of a case.
AB  - We report herein the case of a 33-year-old woman who presented with palpable
      abdominal swelling found to be caused by a huge lymphangioma of the pancreas. An
      abdominal computed tomographic (CT) scan showed a large multilocular cystic mass
      with water-dense contents, which was derived from the pancreatic head. A
      pancreaticoduodenectomy (PD) was performed because the tumor had invaded the
      duodenum. The resected tumor, which was 23 x 12 x 23 cm in size with 21 of serous
      fluid, was pathologically diagnosed as a cystic lymphangioma. The endothelial
      cells lining the internal surface of the cystic spaces were immunohistochemically
      positive for factor VIII-R antigen and CD31. Our review of the literature
      revealed 45 reports of lymphangioma of the pancreas, including this one, but to
      the best of our knowledge this is only the fifth case that required a PD.
      Nevertheless, we recommend that a complete resection be performed to reduce the
      risk of recurrence.

PMID- 11510618
TI  - Mucinous cystadenocarcinoma of the retroperitoneum: report of a case.
AB  - Retroperitoneal mucinous cystadenocarcinomas are extremely rare. A 40-year-old
      Japanese woman was found to have a retroperitoneal mucinous cystadenocarcinoma of
      ovarian type. Both ovaries were normal. Concentrations of carcinoembryonic
      antigen and carbohydrate antigen 19-9 in the cyst fluid were extremely high
      (810,000 ng/ml and 8,082,000 IU/l, respectively). The tumor varied from benign to
      borderline and malignant in microscopic appearance, and the lesion was composed
      of mesothelium-like cells. The histologic and immunohistochemical findings
      suggested that the tumor developed from mucinous metaplasia of the coelomic
      mesothelium.

PMID- 11510619
TI  - Pseudoaneurysm of the left gluteal artery after a pelvic fracture sustained
      during the Marmara earthquake: report of a case.
AB  - Although iliac artery injuries caused by pelvic fractures are uncommon, in
      special circumstances, such as earthquakes, traumatic arterial injury should be
      carefully investigated. This reports describes a case of an iliac artery
      pseudoaneurysm causing compressive symptoms that was successfully treated by
      radiologic embolization.

PMID- 11510620
TI  - Staged vascular reconstruction along with repeatedly performed angiography to
      prevent ischemic limb loss with Buerger's disease: report of a case.
AB  - An aggressive approach to vascular reconstruction should be adopted in patients
      with Buerger's disease and peripheral ischemia who are often young and otherwise
      active. A patient with severe Buerger's disease is reported who was treated
      successfully by complete vascular reconstruction with staged bypass surgery while
      also performing repeated angiography to preserve the foot function. A 48-year-old
      man with Buerger's disease presented with necrosis of the foot. Angiography
      showed occlusion of the right distal external iliac artery and no runoff below
      the knee. Repeated angiography after performing a lumbar sympathectomy
      demonstrated patency of the distal portion of the deep femoral artery.
      Angiography was again performed after a reconstruction of the deep femoral artery
      and patency of the anterior tibial artery was observed. A staged bypass operation
      on the tibial artery was therefore able to achieve a prompt healing of both the
      toe ulcers and plantar wound.

PMID- 11510621
TI  - Vaccines against nicotine: how effective are they likely to be in preventing
      smoking?
AB  - Cigarette smoking is the most preventable cause of death in industrialised
      countries. 30% of all deaths in smokers in the 35 to 69 years age range are
      attributed to chronic cigarette smoking; smokers dying in this age cohort lose an
      average of 23 years of life. Public health campaigns have attempted to reduce
      initiation of smoking in adolescents and to foster quitting in dependent smokers.
      The prevalence of smoking has declined in the US to 25% of the population, but
      this figure has held constant for the last decade. Vaccines against nicotine are
      a novel concept in the field of smoking cessation research and have not yet
      reached the stage of clinical testing. Vaccines could reduce smoking behaviour in
      3 groups of smokers: (i) current smokers attempting to quit; (ii) former smokers
      wanting to avoid the possibility of relapse; and (iii) adolescent smokers before
      they become confirmed smokers. The rationale behind the approach is that nicotine
      is the pharmacological agent controlling the rate of cigarette smoking, and
      reducing its rate and extent of uptake into the brain may have therapeutic
      benefits.

PMID- 11510622
TI  - Stiff man syndrome.
AB  - Stiff man syndrome (SMS), an uncommon neurological disease, is characterised by
      symmetrical muscle stiffness and spasms that often lead to skeletal deformity.
      Variants of the syndrome may involve one limb only (stiff leg syndrome), a
      variety of additional neurological symptoms and signs such as eye movement
      disturbances, ataxia, or Babinski signs (progressive encephalomyelitis with
      rigidity and myoclonus), or be associated with malignant disease (paraneoplastic
      SMS). Antineuronal autoimmunity and accompanying autoimmune diseases, most often
      insulin-dependent diabetes mellitus, are characteristic features of SMS and its
      variants. The condition is frequently misinterpreted as psychogenic movement
      disturbance, but electromyographic abnormalities and the presence of
      autoantibodies against glutamic acid decarboxylase (GAD) in both serum and
      cerebrospinal fluid help to establish the correct diagnosis. The aetiology of SMS
      is obscure. However, several features suggest that SMS is an autoimmune-mediated
      chronic encephalomyelitis. In line with this hypothesis, immunomodulation with a
      front-loaded methylprednisolone regimen reduces stiffness and spasms and improves
      other neurological symptoms in the majority of patients. Plasmapheresis or
      intravenous immunoglobulins are effective less frequently. For symptomatic
      treatment, the benzodiazepines are drugs of first choice. An alternative of last
      resort is baclofen administered intrathecally via an implanted pump device.

PMID- 11510623
TI  - General anaesthesia for supratentorial neurosurgery.
AB  - Anaesthesia for the surgical treatment of supratentorial tumours requires an
      understanding of: the pathophysiology of a localised or generalised increase in
      intracranial pressure (ICP), the regulation and maintenance of intracerebral
      perfusion, avoidance of secondary systemic insults to the brain, and the effects
      of anaesthetic drugs on ICP, cerebral perfusion and cerebral metabolism.
      Knowledge of the therapeutic options available for decreasing ICP, brain bulk and
      brain tension perioperatively is also essential. Potential complications which
      may present during supratentorial neurosurgery include massive intraoperative
      haemorrhage and seizures. The fact that the surgeon is operating on a tensed
      brain is also a potential source of difficulty. The need to monitor brain
      function and environment during surgery poses a challenge to the
      anaesthesiologist, as does the achievement of rapid emergence from anaesthesia
      with the adequate use of anaesthetic drugs.

PMID- 11510624
TI  - Bodyweight gain associated with atypical antipsychotics: epidemiology and
      therapeutic implications.
AB  - Atypical antipsychotic medications are associated with different adverse effects
      and efficacy profiles compared with conventional antipsychotics (i.e. less
      extrapyramidal symptoms, improved-efficacy against negative symptoms and
      cognitive deficits, and most often a greater ability to improve patients' quality
      of life). However, the atypical antipsychotics may be associated with clinically
      significant bodyweight gain, increasing the risk of medical comorbidity,
      including diabetes mellitus, hypertension, cardiovascular disease and
      hyperlipidaemia. This literature review assesses the various bodyweight gain
      liabilities associated with atypical antipsychotics, as well as the effects of
      bodyweight gain on quality of life. The issue of prevention and management of
      this often neglected adverse effect is also examined. Most studies reviewed
      indicate that clozapine and olanzapine are associated with more bodyweight gain
      than the other atypical antipsychotics. There are potential factors that place
      certain patients at greater risk for bodyweight gain, including low pretreatment
      body mass index, young age and being of female gender. Furthermore, bodyweight
      gain associated with the use of atypical antipsychotics has been reported to be
      associated with clinical improvement, although this has not been substantiated
      widely. It is unclear whether increased medical comorbidity, including diabetes
      mellitus, coronary artery disease and/or elevated triglyceride levels, is
      secondary to the bodyweight gain associated with atypical antipsychotics, or the
      result of the agents themselves. A patient's quality of life may be greatly
      affected by excessive bodyweight gain; either by increased comorbid medical
      illness, an increased relapse rate associated with noncompliance, or the social
      stigma associated with being obese. However, most studies reveal that treatment
      with atypical antipsychotic medications is associated with improved quality of
      life compared with that achieved with conventional antipsychotic medications.
      Because bodyweight is an important health risk associated with atypical
      antipsychotics, prevention and effective management of bodyweight are paramount
      in preventing comorbid medical illness, relapse and possible noncompliance.

PMID- 11510627
TI  - Clinical pharmacokinetics of mizolastine.
AB  - Mizolastine is a new histamine H1 receptor antagonist. Mizolastine 10 mg/day is
      effective in allergic rhinitis and chronic idiopathic urticaria. In young healthy
      volunteers, absorption of mizolastine is rapid with time (tmax) to peak
      concentration (Cmax) of about 1 hour. The absolute bioavailability of mizolastine
      10mg tablets is about 65%. Distribution is rapid with a mean distribution half
      life of 1.5 to 1.9 hours. Mizolastine is >98% bound to serum albumin and the
      apparent volume of distribution is between I and 1.4 L/kg. Mizolastine is
      extensively metabolised by hepatic glucuronidation and sulphation, with no major
      active metabolite, and excreted in faeces. The terminal elimination half-life
      (t1/2beta) is 7.3 to 17.1 hours. The apparent oral clearance after a repeated
      oral dose of 10mg is 6.02 L/h, with steady state reached from day 3 and no
      accumulation between days 1 and 7. Cmax and area under the concentration-time
      curve (AUC) are linearly related to dose. Mizolastine appears in vivo to be a
      relatively weak inhibitor of cytochrome P450 2E1, 2C9, 2D6 and 3A4. In vivo, no
      interactions were observed between mizolastine and lorazepam or ethanol. A
      significant increase in Cmax and trough plasma concentration (Cmin) of digoxin
      occurred after coadministration with mizolastine, without change in AUC, tmax or
      clinical parameters. Significant increases in theophylline Cmin and AUC were
      observed after coadministration with mizolastine. Mizolastine Cmax and AUC were
      increased when coadministered with erythromycin, with no change in t1/2beta.
      Concomitant administration of mizolastine and ketoconazole increased mizolastine
      AUC values with no change in t1/2beta. In a population analysis of the
      pharmacokinetics of mizolastine in patients with allergies, parameter values were
      close to those in healthy volunteers, except for duration of absorption, which
      was almost doubled in the patients. Bodyweight and creatinine clearance were
      found to have little influence on oral clearance, and no influence of liver
      transaminases was found on clearance and distribution. Pharmacokinetic parameters
      of mizolastine in elderly individuals were similar to those observed in healthy
      young volunteers. In patients with chronic renal insufficiency, t1/2beta was
      prolonged by 47% compared with young healthy volunteers. In patients with
      cirrhosis, tmax was longer, Cmax was lower, distribution half-life was prolonged
      and AUC was 50% higher than in healthy volunteers. In pharmacodynamic
      pharmacokinetic trials, the percentage of wheal and flare inhibition was found to
      correlate with mizolastine Cmin values. No direct relationship was found between
      drug concentrations in skin blister fluid and antihistamine activity.

PMID- 11510625
TI  - Pharmacological treatment of traumatic brain injury: a review of agents in
      development.
AB  - Successful treatment strategies for patients with traumatic brain injury (TBI)
      remain elusive despite standardised clinical treatment guidelines, improved
      understanding of mechanisms of cellular response to trauma, and a decade of
      clinical trials aimed at identifying therapeutic agents targeted at mediators of
      secondary injury. The information explosion relative to mechanisms of secondary
      injury has identified several potential targets for intervention. Depending on
      the type of injury to the brain and the intensity and the success of
      resuscitation, necrosis, apoptosis, inflammatory and excitotoxic cellular damage
      can be seen. These same processes may continue postinjury, depending on the
      adequacy of clinical care. Each of these mechanisms of cellular damage can
      initiate a cascade of events mediated by endogenous signals that lead to
      secondary neurological injury. Several factors contributed to the failure of
      earlier clinical trials. Now that these have been recognised, a positive impact
      on future drug development in TBI has been realised. Both the US and Europe have
      organised brain injury consortiums where experts in the treatment of TBI provide
      insight into study design, implementation, conduct and oversight in conjunction
      with the pharmaceutical industry. Consequently, future clinical trials of new
      investigational treatments have greater potential for identifying therapies of
      merit in specific populations of patients with TBI. Pharmacological strategies
      under investigation are targeting sites involved in the secondary cascade that
      contribute to overall poor outcome following the primary injury. These treatments
      include ion channel antagonists including calcium channel antagonists, growth
      factors, antioxidants, stem cells, apoptosis inhibitors, and inhibitors of other
      signal modulators. In conclusion, the complexity of TBI pathology and the
      mechanisms contributing to secondary injury present unique therapeutic
      challenges. Appropriate research targets for intervention continue to be
      investigated, however, the likelihood of improving outcomes with a single
      approach is extremely small. There is a need for collaborative efforts to
      investigate the optimal time for drug administration and the logical sequence or
      combination of treatments that will ultimately lead to improved neurological
      outcomes in this population.

PMID- 11510626
TI  - Morphine-6-glucuronide: an analgesic of the future?
AB  - Morphine-6-beta-glucuronide (M6G) is an opioid agonist that plays a role in the
      clinical effects of morphine. Although M6G probably crosses the blood-brain
      barrier with difficulty, during long term morphine administration it may reach
      sufficiently high CNS concentrations to exert clinically relevant opioid effects.
      As a consequence of its almost exclusive renal elimination, M6G may accumulate in
      the body of patients with impaired renal function and cause severe opioid adverse
      effects with insidious onset and long persistence. Its profile of receptor
      affinities, however, gives reason to speculate that M6G may exhibit analgesic
      effects while causing fewer adverse effects than morphine. This is supported by
      reports of the good tolerability of intrathecal and intravenous injections of M6G
      in humans with intact renal function. M6G may thus be contemplated as an
      analgesic for short term postoperative analgesia, especially for intrathecal
      analgesic therapy. In addition, its possibly higher potency than morphine makes
      M6G a candidate opioid for local or peripheral analgesic therapy. However,
      current knowledge is too incomplete to finally judge the clinical usefulness of
      M6G. The next topics for clinical research on M6G should include: (i) a
      comparison of the potencies of M6G and morphine to cause wanted and unwanted
      clinical effects; (ii) development of a predictive population pharmacokinetic
      pharmacodynamic model of M6G with calculation of the transfer half-life between
      plasma and effect site; and (iii) identification of cofactors influencing the
      action of M6G that can serve as predictors for the clinical outcome of
      morphine/M6G therapy in an individual including the pharmacogenetics of M6G.

PMID- 11510628
TI  - Clinical pharmacokinetics of quetiapine: an atypical antipsychotic.
AB  - Quetiapine is a dibenzothiazepine derivative that has been evaluated for
      management of patients with the manifestations of psychotic disorders. In
      pharmacokinetic studies in humans, quetiapine was rapidly absorbed after oral
      administration, with median time to reach maximum observed plasma concentration
      ranging from 1 to 2 hours. The absolute bioavailability is unknown, but the
      relative bioavailability from orally administered tablets compared with a
      solution was nearly complete. Food has minimal effects on quetiapine absorption.
      The drug is approximately 83% bound to serum proteins. Single and multiple dose
      studies have demonstrated linear pharmacokinetics in the clinical dose range (up
      to 375mg twice daily). The drug is eliminated with a mean terminal half-life of
      approximately 7 hours. The primary route of elimination is through hepatic
      metabolism. In vitro studies show that quetiapine is predominantly metabolised by
      cytochrome P450 (CYP) 3A4. After administration of [14C]quetiapine, approximately
      73% of the radioactivity was excreted in the urine and 21% in faeces. Quetiapine
      accounted for less than 1% of the excreted radioactivity. 11 metabolites formed
      through hepatic oxidation have been identified. Two were found to be
      pharmacologically active, but they circulate in plasma at 2 to 12% of the
      concentration of quetiapine and are unlikely to contribute substantially to the
      pharmacological effects of the drug. The pharmacokinetics of quetiapine do not
      appear to be altered by cigarette smoking. Oral clearance declines with age, and
      was reduced in 2 of 8 patients with hepatic dysfunction but not in patients with
      renal impairment. Quetiapine has no effect on the in vitro activity of CYP1A2,
      2C9, 2C19, 2D6 and 3A4 at clinically relevant concentrations. The lack of effect
      of quetiapine on hepatic oxidation was confirmed in vivo by the lack of effect of
      quetiapine on antipyrine disposition. Quetiapine had no effect on serum lithium
      concentration. Phenytoin and thioridazine increase the clearance of quetiapine,
      and ketoconazole decreases clearance. No clinically significant effects of
      cimetidine, haloperidol, risperidone or imipramine on the pharmacokinetics of
      quetiapine were noted. Quetiapine dosage adjustment, therefore, may be necessary
      when coadministered with phenytoin, thioridazine or other potent CYP3A4 inducers
      or inhibitors. The relationship between the therapeutic effects and the plasma
      concentrations of quetiapine has been investigated in a multicentre clinical
      trial. There was no statistically significant association between trough plasma
      quetiapine concentration and clinical response as measured by traditional
      assessments of psychotic symptom severity. Subsequent clinical studies of the
      plasma concentration versus effect relationships for quetiapine may help to
      further define guidelines for dosage regimen design.

PMID- 11510629
TI  - Drug interaction studies with esomeprazole, the (S)-isomer of omeprazole.
AB  - Esomeprazole, the (S)-isomer of omeprazole, is the first proton pump inhibitor
      (PPI) developed as a single isomer for the treatment of patients with acid
      related diseases. Because of the extensive use of PPIs, the documentation of the
      potential for drug interactions with esomeprazole is of great importance. Altered
      absorption or metabolism are 2 of the major mechanisms for drug-drug
      interactions. Since intragastric pH will increase with esomeprazole treatment, it
      can be hypothesised that the absorption of drugs with pH-sensitive absorption
      (e.g. digoxin and ketoconazole) may be affected. Esomeprazole does not seem to
      have any potential to interact with drugs that are metabolised by cytochrome P450
      (CYP) 1 A2, 2A6, 2C9, 2D6 or 2E1. In drug interaction studies with diazepam,
      phenytoin and (R)-warfarin, it was shown that esomeprazole has the potential to
      interact with CYP2C19. The slightly altered metabolism of cisapride was also
      suggested to be the result of inhibition of a minor metabolic pathway for
      cisapride mediated by CYP2C19. Esomeprazole did not interact with the CYP3A4
      substrates clarithromycin (2 studies) or quinidine. Since the slightly increased
      area under the concentration-time curve (AUC) of cisapride could be explained as
      an inhibition of CYP2C19, the data on these 3 CYP3A4 substrates indicate that
      esomeprazole does not have the potential to inhibit this enzyme. The minor
      effects reported for diazepam, phenytoin, (R)-warfarin, and cisapride are
      unlikely to be of clinical relevance. Clarithromycin interacts with the
      metabolism of esomeprazole resulting in a doubling of the AUC of esomeprazole.
      The increased plasma concentrations of esomeprazole are unlikely to have any
      safety implications. It can be concluded that the potential for drug-drug
      interactions with esomeprazole is low, and similar to that reported for
      omeprazole.

PMID- 11510631
TI  - Prediction of hepatic metabolic clearance: comparison and assessment of
      prediction models.
AB  - OBJECTIVE: To perform a comparative quantitative evaluation of the prediction
      accuracy for human hepatic metabolic clearance of 5 different mathematical
      models: allometric scaling (multiple species and rat only), physiologically based
      direct scaling, empirical in vitro-in vivo correlation, and supervised artificial
      neural networks. METHODS: The mathematical prediction models were implemented
      with a publicly available dataset of 22 extensively metabolised compounds and
      compared for their prediction accuracy using 3 quality indicators: prediction
      error sum of squares (PRESS), r2 and the fold-error. RESULTS: Approaches such as
      physiologically based direct scaling, empirical in vitro-in vivo correlation and
      artificial neural networks, which are based on in vitro data only, yielded an
      average fold-error ranging from 1.64 to 2.03 and r2 values greater than 0.77, as
      opposed to r2 values smaller than 0.44 when using allometric scaling combining in
      vivo and in vitro preclinical data. The percentage of successful predictions
      (less than 2-fold error) ranged from 55% (rat allometric scaling) to between 64
      and 68% with the other approaches. CONCLUSIONS: On the basis of a diverse set of
      22 metabolised drug molecules, these studies showed that the most cost-effective
      and accurate approaches, such as physiologically based direct scaling and
      empirical in vitro-in vivo correlation, are based on in vitro data alone.
      Inclusion of in vivo preclinical data did not significantly improve prediction
      accuracy; the prediction accuracy of the allometric approaches was at the lower
      end of all methods compared.

PMID- 11510630
TI  - Pegylation: a novel process for modifying pharmacokinetics.
AB  - The use of liposomal carriers and the modification of therapeutic molecules
      through the attachment of poly(ethylene glycol) [PEG] moieties ('pegylation') are
      the most common approaches for enhancing the delivery of parenteral agents.
      Although 'classical' liposomes (i.e. phospholipid bilayer vehicles) have been
      effective in decreasing the clearance of encapsulated agents and in passively
      targeting specific tissues, they are associated with considerable limitations.
      Pegylation may be an effective method of delivering therapeutic proteins and
      modifying their pharmacokinetic properties, in turn modifying pharmacodynamics,
      via a mechanism dependent on altered binding properties of the native protein.
      Pegylation reduces renal clearance and, for some products, results in a more
      sustained absorption after subcutaneous administration as well as restricted
      distribution. These pharmacokinetic changes may result in more constant and
      sustained plasma concentrations, which can lead to increases in clinical
      effectiveness when the desired effects are concentration-dependent. Maintaining
      drug concentrations at or near a target concentration for an extended period of
      time is often clinically advantageous, and is particularly useful in antiviral
      therapy, since constant antiviral pressure should prevent replication and may
      thereby suppress the emergence of resistant variants. Additionally, PEG
      modification may decrease adverse effects caused by the large variations in peak
      to-trough plasma drug concentrations associated with frequent administration and
      by the immunogenicity of unmodified proteins. Pegylated proteins may have reduced
      immunogenicity because PEG-induced steric hindrance can prevent immune
      recognition. Two PEG-modified proteins are currently approved by the US Food and
      Drug Administration; several others, including cytokines such as interferon-alpha
      (IFNalpha), growth factors and free radical scavengers, are under development.
      Careful assessment of various pegylated IFNalpha products suggests that pegylated
      molecules can be differentiated on the basis of their pharmacokinetic properties
      and related changes in pharmacodynamics. Because the size, geometry and
      attachment site of the PEG moiety play a crucial role in determining these
      properties, therapeutically optimised agents must be designed on a protein-by
      protein basis.

PMID- 11510632
TI  - Comparison of condylar position in hyperdivergent and hypodivergent facial
      skeletal types.
AB  - Orthodontists have long been interested in the differences in the diagnosis and
      treatment of hyperdivergent and hypodivergent facial types. More recently, many
      orthodontists have become interested in treating to a seated condylar position or
      centric relation. It was the objective of this study to investigate the
      difference in condylar position between these 2 extreme facial types. Two groups
      of 33 subjects, each representing the extremes in facial type, were randomly
      selected and matched for age and sex. Mounted casts and the MPI instrumentation
      were used to measure and compare the amount of condylar distraction between the 2
      groups in the horizontal and vertical planes. The total amount of change between
      the 2 groups was examined using a statistical t-test. There was a statistically
      significant greater distraction of the condyles in the hyperdivergent group in
      both the horizontal and vertical planes.

PMID- 11510633
TI  - Initial stress differences between sliding and sectional mechanics with an
      endosseous implant as anchorage: a 3-dimensional finite element analysis.
AB  - Endosseous implants have been used as orthodontic anchorage in recent years. A 3
      dimensional mathematical model was constructed that uses the finite element
      method, which simulated an endosseous implant and an upper canine with its
      periodontal ligament and cortical and cancellous bone. Levels of initial stress
      were measured during 2 types of canine retraction mechanics (friction and
      frictionless). The lower magnitude and more uniform stresses in the implant and
      its cortical bone were found to have a moment-force ratio (M/F) of 6.1:1, whereas
      the canine and its supporting structures exerted a M/F ratio of 10.3:1. On the
      basis of these results, when the anchor unit is an endosseous implant, it seems
      better to use a precalibrated retraction system without friction (T-loop) where a
      low load-deflection curve would be generated.

PMID- 11510634
TI  - Three-dimensional inclination of the dental axes in healthy permanent dentitions-
      A cross-sectional study in a normal population.
AB  - The 3-dimensional (3-D) inclination of the facial axis of the clinical crown
      (FACC) and the size of the clinical crowns were measured in 100 white northern
      Italians. The subjects consisted of 22 girls and 21 boys, ages 13-15 years
      (adolescents), and 31 women and 26 men, ages 16-26 years (adults), all with a
      complete permanent dentition and Class I dental relationships. The 3-D
      coordinates of dental landmarks were obtained with a computerized electromagnetic
      digitizer. Clinical crowns heights and FACC inclinations in the anatomical
      frontal and sagittal planes relative to 2 reference planes, maxillary and
      mandibular (between the incisive papilla and the intersection of the
      palatal/lingual sulci of the first permanent molars with the gingival margin),
      were calculated. Ages and sexes were compared by ANOVA. On average, the frontal
      plane FACCs of most teeth converged toward the midline plane of symmetry. In
      contrast, the incisors diverged from the midline plane or were nearly vertical.
      Within each quadrant, the inclinations of the postincisor teeth progressively
      increased. In the sagittal plane, most teeth had a nearly vertical FACC. FACC
      inclinations showed sex- and age-related differences (P < .05). In the frontal
      plane, the canines, premolars, and molars were more inclined in adolescents than
      in adults. In the sagittal plane, a large within-group variability was observed.
      Clinical crown height was significantly larger in males than in females in all
      maxillary and mandibular canines, premolars, second molars, maxillary central
      incisors, and first molars. With age, some degree of dental eruption was found in
      maxillary and mandibular canines, maxillary second premolars, and molars. The age
      related decrease in FACC inclination may be the effect of a progressive buccal
      and mesial drift.

PMID- 11510635
TI  - Effects of bisphosphonate on the remodeling of rat sagittal suture after rapid
      expansion.
AB  - The purpose of this study was to investigate the effects of bisphosphonate (BP),
      an inhibitor of bone resorption, on the remodeling of the rat sagittal suture
      after rapid expansion. Wistar strain male rats were divided into 4 groups and
      subjected to rapid mechanical expansion with an initial force of 60 g for 3 days.
      Immediately after the sutural expansion, the appliance was removed in 2 of the
      groups. In the S group, half of the animals were injected with saline solution
      daily for 3 days and the other half were injected daily for 7 days prior to
      sacrifice. In the B group, half of the animals were injected with bisphosphonate
      daily for 3 days and the other half were injected daily for 7 days prior to
      sacrifice. The remaining 2 groups underwent 7 days of mechanical retention before
      the appliance was removed. In the SR group, half of the animals were injected
      with saline solution daily for 3 days and the other half were injected daily for
      7 days prior to sacrifice. In the BR group, half of the animals were injected
      with bisphosphonate solution daily for 3 days and the other half were injected
      daily for 7 days prior to sacrifice. The calvariae were fixed in 4% neutral
      formalin, decalcified, and embedded in paraffin. The amount of relapse and the
      relevant bone remodeling were evaluated in terms of a relapse ratio and the
      number of osteoclasts. The relapse ratio was 54.11% in the S group and 32.53% in
      the B group 7 days after the injection. This ratio was 25.13% in the SR group and
      9.60% in the BR group. The number of osteoclasts 3 days after injection was 15.47
      in the S group, which was significantly greater than the 5.26 present in the B
      group. This number was 7.08 in the SR group, which was significantly greater than
      the 1.83 in the BR group. These results demonstrate that the injection of BP
      after rapid expansion, if combined with mechanical retention, may produce more
      secure retention by inhibiting bone resorption, indicating a possibility of
      employing a pharmaceutical aid to decrease the skeletal relapse after
      mechanotherapy in clinical orthodontics.

PMID- 11510636
TI  - Craniofacial morphology in children with complete unilateral cleft lip and
      palate: a comparison of two surgical protocols.
AB  - The facial morphology of 2 groups of complete unilateral cleft lip and palate
      children (n = 75), ranging in age from 4 to 7 years old, were retrospectively
      studied cephalometrically before the beginning of the orthodontic treatment. Each
      group was submitted to a different surgical protocol. The control group was
      comprised of 53 children (33 males and 20 females) and was treated according to
      the surgical protocol of the Hospital for Rehabilitation of Craniofacial
      Anomalies (HRCA) from the University of Sao Paulo, in Bauru, Brazil. Lip repair
      was performed between 3 months and 27 months of age (mean age of 9 months) and
      palate repair between 12 months and 44 months of age (mean age of 19 months). The
      experimental group was comprised of 22 children (12 males and 10 females). They
      were treated with Malek's surgical protocol, modified at the HRCA, with lip and
      soft palate repair at 5.5 months of age on average and hard palate repair at 20
      months of age on average. The cephalometric results did not show any difference,
      suggesting that both surgical protocols have the same influence on facial growth,
      at least during the age range studied. Therefore, palate repair in 2 surgical
      times with earlier closure of the soft palate (Malek's protocol) did not cause
      greater restriction to the midface growth.

PMID- 11510637
TI  - New posteroanterior cephalometric norms: a comparison with craniofacial measures
      of children treated with palatal expansion.
AB  - The aim of the study was to evaluate posteroanterior (PA) cephalometric
      characteristics in a normal longitudinal database and compare these measurements
      with corresponding measures in a group of patients treated with rapid maxillary
      expansion. Posteroanterior cephalographs of 16 girls and 14 boys from the Bolton
      Brush growth study, taken at ages 10 and 18 years, were used to track growth in
      children with normal occlusion. Pretreatment PA cephalograms of 24 patients who
      had palatal distraction around age 10 were compared with the 10-year-old normal
      patients. Digitized landmarks included right and left jugale (J, at intersection
      of maxillary tuberosity and zygomatic buttress) and antegonion (AG, at notch of
      antegonial protuberance). Mandibular width (AG-AG) was similar in boys and girls
      at age 10 but not 18, when the difference between gender groups was statistically
      significant (P < .05). Maxillary width (J-J) was greater in boys than girls at
      both ages. The increase in AG-AG (5.5 mm, boys; 3.9 mm, girls) was more than
      twice that of J-J (2.4 mm, boys; 1.2 mm, girls). Arch width (at first molar) was
      nearly stable with age, indicating compensatory occlusal adaptation to
      differential changes between maxillary and mandibular widths. At age 18, the
      distance between the centers of the orbits, a surrogate measure of cranial width,
      was almost equal to J-J in girls and significantly correlated with AG-AG in boys
      (r = .71, P < .002) and girls (r = .77, P < .0001). The majority of treated
      children had both skeletal and dentoalveolar widths narrower than control values.
      Linear regressions between J-J and AG-AG revealed almost parallel slopes for
      control and treated groups in both genders, but the treated group was at a lower
      level, which is consistent with smaller maxillary widths.

PMID- 11510638
TI  - An assessment of root cementum in cleidocranial dysplasia.
AB  - The purpose of this prospective study was to determine if there is a difference
      between the amount of cellular and acellular cementum on the roots of 2 teeth
      extracted from a subject with cleidocranial dysplasia (CCD) compared to 10 teeth
      extracted from 10 subjects unaffected by CCD. The cementum of 2 permanent teeth,
      which had been extracted from the CCD subject, was examined and
      histomorphometrically analyzed for comparison to the cementum of 10 anterior
      teeth that had been extracted from individuals who were unaffected by CCD. The
      percentage of the root covered by cellular or acellular cementum was quantified
      to determine if patients affected by CCD typically lack cellular cementum. In the
      roots of the 2 permanent teeth of the subject with CCD, a mean of 18.05 +/-
      10.67% was covered by cellular cementum and 76.90 +/- 3.53% was covered by
      acellular cementum. In the 10 permanent teeth from subjects without CCD, a mean
      of 19.12 +/- 15.60% of the root was covered by cellular cementum and 80.34 +/-
      15.71% was covered by acellular cementum. The findings indicate that there is no
      statistically significant difference between the amount of either cellular or
      acellular cementum covering the roots of the study subject with CCD and the roots
      of the 10 control teeth. The presumption that a lack of cellular cementum causes
      the increased number of unerupted teeth in patients with CCD is not supported by
      the findings of this study.

PMID- 11510639
TI  - Evaluation of aerosol contamination during debonding procedures.
AB  - The aim of this study was to show how the aerosol generated by the use of an air
      turbine handpiece during debonding procedures increases the potential risk factor
      for the distribution of infectious agents. A second aim of the study was to
      evaluate the effectiveness of a preprocedural chlorhexidine mouth rinse in
      reducing the number of colony forming units (CFU) found in aerosol samples. Blood
      agar plates were attached to the face shields and the dental chair table and were
      used for collecting the aerosol samples. In the first part of the study, 260
      samples were collected for the baseline group in an empty room, 36 samples were
      collected for the control group (C), in which the orthodontist, dental assistant,
      and the patient were in the operatory room, and 42 samples were collected for the
      debonding group (DB). The microbiologic analysis showed significant differences
      between the baseline group and the control group (P < .05). Furthermore, aerosol
      contamination increased significantly during the debonding procedure when
      compared with the control group (P < .01). In the second part of the study, an
      air turbine handpiece was used to remove excess adhesive from the tooth surface
      on one side of the mouth and air samples were collected. The patients then were
      instructed to rinse their mouths with 0.2% chlorhexidine gluconate for 1 minute,
      and the orthodontist worked on the other side of the mouth and the air sampling
      was repeated. An insignificant reduction was found in the number of colony
      forming units following the chlorhexidine mouth rinse. Results of this study
      indicated that orthodontists are exposed to high levels of aerosol generation and
      contamination during the debonding procedure, and preprocedural chlorhexidine
      gluconate mouth rinse appears to be ineffective in decreasing the exposure to
      infectious agents. Therefore, barrier equipment should be used to prevent aerosol
      contamination.

PMID- 11510640
TI  - Bracket bond strength with transillumination of a light-activated orthodontic
      adhesive.
AB  - The literature describes transillumination as a means of curing orthodontic light
      cured composite adhesive. The literature also recommends a 2 to 3 times increase
      in light exposure time when light curing using transillumination. The purpose of
      this study was to determine the transmittance of the curing light through human
      enamel and the effect of transillumination on the bond strength of orthodontic
      brackets. One hundred extracted human maxillary incisors were used in this study.
      Brackets with orthodontic composite adhesive were placed on the labial surface of
      the incisors and light cured from either the labial or the lingual
      (transillumination). The control sample was cured from the labial for a total of
      40 seconds of light exposure. Experimental samples were cured from the lingual
      (transillumination) for 20, 30, 40, or 50 seconds. The shear-peel bond strengths
      were tested at 30 minutes and 24 hours after light application. The results of
      this study demonstrated no statistically significant difference between 40
      seconds of labial curing and most of the lingually cured groups. The only
      experimental group that differed statistically from the control group was the 40
      second lingual cure group tested at 30 minutes after light application. Actual
      bond strengths, however, were lower for all experimental samples. The samples
      tested at 24 hours that received 50 seconds of transillumination were nearly the
      same as the control values. This study demonstrated that transillumination of
      maxillary incisors is an acceptable method of curing orthodontic adhesive,
      particularly if the exposure time is increased from 40 to 50 seconds.

PMID- 11510641
TI  - In vitro bond strengths of resin modified glass ionomer cements and composite
      resin self-cure adhesives: introduction of an adhesive system with increased bond
      strength and inhibition of decalcification.
AB  - This study evaluated the shear bond strength and adhesive remnant index of 5 self
      cure adhesives to comparatively evaluate a new adhesive system. Extracted human
      incisors were randomly divided into 7 test groups of 20 each. Incisor mesh-backed
      brackets were bonded to the tooth specimens in each group with their respective
      adhesive according to the manufacturer's instructions. The specimens were
      thermocycled for 2 weeks at temperatures from 5 degrees to 55 degrees C to
      simulate oral conditions and debonded using an Instron machine. Acceptable bond
      strength parameters were present with the Contacto No-Mix (composite resin
      containing glass ionomer 8.75 MPa) and Fuji Ortho SC with acid conditioning (6.98
      MPa). Contacto No-Mix had a higher bond strength (11.2 MPa) when microetching and
      Megabond were employed than when these adjuncts were not employed. When FUJI
      Ortho SC specimens were conditioned with polyacrylic acid, they showed a higher
      bond strength (6.98 MPa) than when bonded to unetched teeth (5.41 MPa). In test
      3, EXPT-fluoride adhesive (AF) demonstrated a higher bond strength (13.44 MPa)
      than both resin composite Contacto No-Mix (8.8 MPa, GAC 7.4 MPa) and FUJI Ortho
      SC (5.41 MPa). Expt AF (Test 3) and Concise had equal bond strengths, however,
      the former can potentially release fluoride from the glass ionomer. Although the
      Ex

PMID- 11510642
TI  - Sensitivity of titanium brackets to the corrosive influence of fluoride
      containing toothpaste and tea.
AB  - Titanium brackets are used in orthodontic patients with an allergy to nickel and
      other specific substances. In recent studies, the corrosive properties of
      fluoride-containing toothpastes with different pH values were investigated. The
      present in vivo study tested how the surfaces of titanium brackets react to the
      corrosive influence of acidic fluoride-containing toothpaste during orthodontic
      treatment. Molar bands were placed on 18 orthodontic patients. In these same
      patients, titanium brackets were bonded on the left quadrants and stainless steel
      brackets on the right quadrants of the upper and lower arches. Fifteen patients
      used Gel Kam containing soluble tin fluoride (pH 3.2), whereas 3 used fluoride
      free toothpaste. The brackets were removed for evaluation by light microscopy and
      scanning microscopy 5.5 to 7.0 months and 7.5 to 17 months after bonding. The
      quality and quantity of elements present were measured by scanning microscopy.
      Macroscopic evaluation showed the matte gray color of titanium brackets
      dominating over the silver gleam of the steel brackets. The plaque accumulation
      on titanium brackets is high because of the very rough surface. Pitting and
      crevices were observed in only 3 of the 165 brackets tested. The present in vivo
      investigation confirms the results of in vitro studies, but the changes are so
      minor that titanium brackets can safely be used for up to 18 months. Wing
      surfaces should be improved by modifying the manufacturing process.

PMID- 11510643
TI  - Development of a proposed standard method for assessing the efficacy of fresh
      produce sanitizers.
AB  - A series of studies was done for the purpose of developing a proposed standard
      method to evaluate point-of-use home sanitizers for fresh produce. Preliminary
      experiments were done to determine the survival of Escherichia coli O157:H7,
      Salmonella, and Listeria monocytogenes after inoculation onto the surface of ripe
      tomatoes and drying for up to 24 h at 22 +/- 2 degrees C. Within 2 h, the initial
      population (6.88 log10 CFU/tomato) of E. coli O157:H7 was reduced by
      approximately 3 log10, while reductions in similar initial populations of
      Salmonella and L. monocytogenes were approximately 1 and 0.6 log10 CFU/tomato,
      respectively, after 40 min and 3 h. A pilot study evaluated treatment with 200
      ppm free chlorine and a prototype Fit produce wash (Fit) for their efficacy in
      killing a five-serotype mixture of Salmonella or L. monocytogenes spot inoculated
      on tomatoes using the proposed inoculation and recovery procedures. Inoculated
      tomatoes were sprayed with chlorinated water, Fit, or sterile distilled water
      (control) and hand rubbed for 30 s. Each tomato was then placed in a plastic bag
      and rinsed with 200 ml of sterile water by vigorously agitating for 30 s to
      simulate a procedure consumers might use for sanitizing and rinsing produce in a
      home setting. Each tomato was transferred to a second bag, and 20 ml of sterile
      0.1% peptone was added; tomatoes were rubbed by hand for 40 s. Populations of
      Salmonella or L. monocytogenes in the rinse water and the 0.1% peptone wash
      solution were determined. Treatment with 200 ppm chlorine and Fit resulted in >
      or = 3.07 and > 6.83 log10 reductions, respectively, in Salmonella. Treatment
      with 200 ppm chlorine and Fit reduced the number of L. monocytogenes by > or =
      3.33 and > or = 4.96 log10 CFU/tomato, respectively. The proposed standard method
      for testing the efficacy of point-of-use produce sanitizers needs to be evaluated
      for reproducibility of results through a larger scale series of experiments.

PMID- 11510644
TI  - Analysis of native microflora and selection of strains antagonistic to human
      pathogens on fresh produce.
AB  - The native microflora of three types of produce (green bell peppers, Romaine
      lettuce, and prepeeled baby carrots) and two types of sprouting seeds (alfalfa
      and clover) were investigated. Aerobic plate count (APC) for each produce or seed
      type as determined on Pseudomonas agar F (PAF) with incubation at 28 degrees C
      was in the range of 4 to 7 log CFU per g of tissue or seed. There was no
      significant difference (P > or = 0.05) in APC when the determinations were made
      with three agar media including PAF, brain heart infusion agar, and plate count
      agar. However, the APC as determined from plates that were incubated at 28
      degrees C was significantly (P < or = 0.05) higher than with incubation at 37
      degrees C. Fluorescent pseudomonads accounted for 23 to 73% of APC and 6 to 18%
      of APC recovered from carrots, pepper, and lettuce were pectolytic. Forty-eight
      strains of pectolytic bacteria were randomly isolated and identified,
      respectively, as members of the genera of Pseudomonas, Erwinia, Bacillus,
      Xanthomonas, or Flavobacterium. Lactic acid bacteria and/or yeast were
      consistently isolated from baby carrots, lettuce, and sprouting seeds (alfalfa or
      clover) but not from green bell peppers. Approximately 120 strains of indigenous
      microflora were tested for their ability to inhibit the growth of Salmonella
      Chester, Listeria monocytogenes, Escherichia coli, or Erwinia carotovora subsp.
      carotovora on PAF. Six isolates capable of inhibiting the growth of at least one
      pathogen were isolated and identified, respectively, as Bacillus spp. (three
      strains), Pseudomonas aeruginosa (one strain), Pseudomonas fluorescens (strain
      A3), and yeast (strain D1). When green pepper disks were inoculated with strains
      A3 and D1, the growth of Salmonella Chester and L. monocytogenes on the disks was
      reduced by 1 and 2 logs, respectively, over a period of 3 days. Application of
      strains A3 and D1 as potential biopreservatives for enhancing the quality and
      safety of fresh produce is discussed.

PMID- 11510645
TI  - Examination of bacteriophage as a biocontrol method for salmonella on fresh-cut
      fruit: a model study.
AB  - The preparation and distribution of fresh-cut produce is a rapidly developing
      industry that provides the consumer with convenient and nutritious food. However,
      fresh-cut fruits and vegetables may represent an increased food safety concern
      because of the absence or damage of peel and rind, which normally help reduce
      colonization of uncut produce with pathogenic bacteria. In this study, we found
      that Salmonella Enteritidis populations can (i) survive on fresh-cut melons and
      apples stored at 5 degrees C, (ii) increase up to 2 log units on fresh-cut fruits
      stored at 10 degrees C, and (iii) increase up to 5 log units at 20 degrees C
      during a storage period of 168 h. In addition, we examined the effect of lytic,
      Salmonella-specific phages on reducing Salmonella numbers in experimentally
      contaminated fresh-cut melons and apples stored at various temperatures. We found
      that the phage mixture reduced Salmonella populations by approximately 3.5 logs
      on honeydew melon slices stored at 5 and 10 degrees C and by approximately 2.5
      logs on slices stored at 20 degrees C, which is greater than the maximal amount
      achieved using chemical sanitizers. However, the phages did not significantly
      reduce Salmonella populations on the apple slices at any of the three
      temperatures. The titer of the phage preparation remained relatively stable on
      melon slices, whereas on apple slices the titer decreased to nondetectable levels
      in 48 h at all temperatures tested. Inactivation of phages, possibly by the
      acidic pH of apple slices (pH 4.2 versus pH 5.8 for melon slices), may have
      contributed to their inability to reduce Salmonella contamination in the apple
      slices. Higher phage concentrations and/or the use of low-pH-tolerant phage
      mutants may be required to increase the efficacy of the phage treatment in
      reducing Salmonella contamination of fresh-cut produce with a low pH.

PMID- 11510646
TI  - Effect of low-temperature, high-pressure treatment on the survival of Escherichia
      coli O157:H7 and Salmonella in unpasteurized fruit juices.
AB  - The destructive effect of high pressure (615 MPa) combined with low temperature
      (15 degrees C) on various strains of Escherichia coli O157:H7 and various
      serovars of Salmonella in grapefruit, orange, apple, and carrot juices was
      investigated. The three-strain cocktail of E. coli O157:H7 (SEA13B88, ATCC 43895,
      and 932) was found to be most sensitive in grapefruit juice (8.34-log reduction)
      and least in apple juice (0.41-log reductions) when pressurized at 615 MPa for 2
      min at 15 degrees C. Correspondingly, no injured survivor was detected in
      grapefruit and carrot juices under similar treatment conditions. No Salmonella
      spp. were detected in a 2-min pressure treatment (615 MPa, 15 degrees C) of
      grapefruit and orange fruit juices. Except for Enteritidis, all four serovars
      tested in the present study have viability loss of between 3.92- and 5.07-log
      reductions when pressurized in apple juice at 615 MPa for 2 min at 15 degrees C.
      No injured cells were recovered from grapefruit and orange juices, whereas the
      same treatment demonstrated reduction in numbers of Salmonella serovars Agona and
      Muenchen in apple juices and to a lesser extent with Typhimurium, Agona, and
      Muenchen in carrot juice. The present study demonstrated that low-temperature,
      high-pressure treatment has the potential to inactivate E. coli O157:H7 strains
      and different Salmonella spp. in different fruit juices.

PMID- 11510647
TI  - Response surface modeling for the inactivation of Escherichia coli O157:H7 on
      green peppers (Capsicum annuum L.) by chlorine dioxide gas treatments.
AB  - The effects of chlorine dioxide (ClO2) gas concentration (0.1 to 0.5 mg/liter),
      relative humidity (RH) (55 to 95%), treatment time (7 to 135 min), and
      temperature (5 to 25 degrees C) on inactivation of Escherichia coli O157:H7 on
      green peppers were studied using response surface methods. A four-factor,
      central, composite, rotatable design was used. The microbial log reduction was
      measured as a response. A direct membrane-surface-plating method with tryptic soy
      agar and sorbitol MacConkey agar was used to resuscitate and enumerate ClO2
      treated E. coli O157:H7 cells. The statistical analysis and the predictive model
      developed in this study suggest that ClO2 gas concentration, treatment time, RH,
      and temperature all significantly (P < 0.01) increased the inactivation of E.
      coli O157:H7. ClO2 gas concentration was the most important factor, whereas
      temperature was the least significant. The interaction between ClO2 gas
      concentration and RH indicated a synergistic effect. The predictive model was
      validated, and it could be used to determine effective ClO2 gas treatments to
      achieve a 5-log reduction of E. coli O157:H7 on green peppers.

PMID- 11510648
TI  - Laying season and egg shell cracks on the growth of Salmonella enteritidis in the
      egg albumen during storage.
AB  - We studied the effects of laying seasons and egg shell cracks on the ability of
      egg albumen to support the growth of Salmonella Enteritidis (SE) in eggs. Hens
      eggs used were those laid in February, June, and October in a farm in Japan and
      stored at 10, 20, and 30 degrees C, and at 30 degrees C after storage at 10
      degrees C, immediately after receipt or after cracking the shell. At several-day
      intervals during storage, the egg contents were poured into a dish, SE was
      inoculated into albumen, and then the growth of SE during 3 days incubation at 18
      degrees C was measured. The results demonstrated that storage temperature and
      laying season affected the growth of SE in the egg albumen. The proportion of
      eggs upon which albumen allowed the growth of SE was higher in the eggs stored at
      30 degrees C than those stored at 10 degrees C. The growth of SE in eggs was
      lowest in the following order of laying: February, October, and June. SE grew
      preferably in albumen of cracked eggs than intact eggs.

PMID- 11510649
TI  - Effect of different levels of beef bacterial microflora on the growth and
      survival of Escherichia coli O157:H7 on beef carcass tissue.
AB  - The influence of various levels of endogenous beef bacterial microflora on the
      growth and survival of Escherichia coli O157:H7 on bovine carcass surface tissue
      was investigated. Bacterial beef microflora inoculum was prepared by enriching
      and harvesting bacteria from prerigor lean bovine carcass tissue (BCT) and was
      inoculated onto UV-irradiated prerigor BCT at initial levels of 10(5), 10(4),
      10(3), and <10(3) CFU/cm2. Additional control BCT was inoculated with sterile
      H2O. E. coli O157:H7 was inoculated onto all tissues at an initial level of 10(2)
      CFU/cm2. Following a 48-h incubation at 4 degrees C, BCT was incubated up to 14
      days at 4 or 12 degrees C, either aerobically or vacuum packaged. Regardless of
      the microflora level, there was no substantial growth of E. coli O157:H7 on BCT
      during storage at 4 degrees C under either aerobic or vacuum-packaged conditions.
      Instead, viable cell numbers at 4 degrees C remained constant, with no reduction
      in numbers associated with the different beef microflora levels. E. coli O157:H7
      grew on all BCT stored at 12 degrees C, regardless of microflora inoculation
      treatment, reaching higher populations on aerobic samples than on vacuum-packaged
      samples in 10 days. However, the presence of the beef microflora did appear to
      delay the onset of growth or slow the growth of the pathogen, and E. coli O157:H7
      counts on BCT without added microflora were generally higher following 7 to 10
      days of 12 degrees C storage than those counts on BCT inoculated with beef
      microflora. These data demonstrate the importance of temperature control during
      meat handling and storage to prevent the outgrowth of this pathogen and indicate
      that proper sanitation and processing practices that prevent and reduce
      contamination of carcasses with E. coli O157:H7 are essential, regardless of
      background microflora levels.

PMID- 11510651
TI  - Influence of lactic acid bacteria on survival of Escherichia coli O157:H7 in
      inoculated Minas cheese during storage at 8.5 degrees C.
AB  - Minas cheese is a typical Brazilian fresh cheese, manufactured by addition of
      rennin and CaCl2 to milk, followed by draining the curd. The intrinsic
      characteristics of this product make it favorable for growth of pathogens,
      including Escherichia coli O157:H7. The influence of the addition of a commercial
      mesophilic type O lactic culture to this product on the growth of this pathogen
      during storage at 8.5 degrees C was evaluated. Eight different formulations of
      Minas cheese were manufactured using raw or pasteurized milk and with or without
      salt and lactic culture. Individual portions of each formulation were transferred
      to sterile plastic bags and inoculated with E. coli O157:H7 to yield ca. 10(3) or
      10(6) CFU/g. After blending by hand massaging the bags, samples were stored at
      8.5 degrees C for up to 14 days. E. coli O157:H7 was counted after 1, 2, 7, and
      14 days of storage using 3M Petrifilm Test Kit-HEC. Counts in samples without
      added lactic culture showed a 2-log increase in the first 24 h and remained
      constant during the following 14 days. Counts in samples with added lactic
      culture showed a 0.5-log increase in the first 24 h, followed by a decrease.
      These variations were statistically significant (P < 0.05). No significant
      variations (P > 0.05) were obtained for cheese samples manufactured with
      pasteurized or raw milk, with or without salt. Results indicate that the addition
      of type O lactic culture may be an additional safeguard to well-established good
      manufacturing practices and hazard analysis and critical control point programs
      in the control of growth of E. coli O157:H7 in Minas cheese.

PMID- 11510650
TI  - Influence of sodium chloride on growth of lactic acid bacteria and subsequent
      destruction of Escherichia coli O157:H7 during processing of Lebanon bologna.
AB  - Due to undesirable quality changes, Lebanon bologna is often processed at
      temperatures that do not exceed 48.8 degrees C (120 degrees F). Therefore, it is
      important to study parameters that influence the destruction of Escherichia coli
      O157:H7 in Lebanon bologna. The objective of the present study was to determine
      the influence of curing salts (NaCl and NaNO2) on the destruction of E. coli
      O157:H7 during Lebanon bologna processing. Fermentation to pH 4.7 at 37.7 degrees
      C reduced populations of E. coli O157:H7 by approximately 0.3 log10, either in
      the presence or absence of curing salts. Subsequent destruction of E. coli
      O157:H7 during heating of fermented product to 46.1 degrees C was significantly
      reduced by the presence of 3.5% NaCl and 156 ppm NaNO2, compared to product
      without curing salts (P < 0.01). The presence of a higher level of NaCl (5%) in
      Lebanon bologna inhibited the growth of lactic acid bacteria (LAB), which yielded
      product with higher pH (approximately 5.0) and significantly reduced the
      destruction of E. coli O157:H7 even further (P < 0.05). Lower concentrations of
      NaCl (0, 2.5%) yielded Lebanon bologna with higher LAB counts and lower pHs,
      compared to product with 5% NaCl. When lactic acid was used to adjust pH in
      product containing different levels of NaCl, it was determined that low pH was
      directly influencing destruction of E. coli O157:H7, not NaCl concentration.

PMID- 11510652
TI  - Validation of a manufacturing process for fermented, semidry Turkish soudjouk to
      control Escherichia coli O157:H7.
AB  - Two soudjouk batters were prepared from ground beef (20% fat) and nonmeat
      ingredients and inoculated with a five-strain mixture of Escherichia coli O157:H7
      to yield an initial inoculum of 7.65 log10 CFU/g. One batter contained a
      commercial-starter culture mixture (approximately 8.0 log10 CFU/g) and dextrose
      (1.5%), while the other batter relied upon a natural fermentation with no added
      carbohydrate. Following mixing, sausage batters were held at 4 degrees C for 24 h
      prior to stuffing into natural beef round casings. Stuffed soudjouk sticks were
      fermented and dried at 24 degrees C with 90 to 95% relative humidity (RH) for 3
      days and then at 22 degrees C with 80 to 85% RH until achieving a product
      moisture level of approximately 40%. After fermentation and drying with an
      airflow of 1 to 1.5 m/s, the sticks were either not cooked or cooked to an
      instantaneous internal temperature of 54.4 degrees C (130 degrees F) and held for
      0, 30, or 60 min. The sticks were then vacuum packaged and stored at either 4 or
      21 degrees C. For each of three trials, three sticks for each treatment/batter
      were analyzed for numbers of E. coli O157:H7 after inoculation, after
      fermentation, after cooking, and after storage for 7, 14, 21, and 28 days.
      Reductions in numbers of E. coli O157:H7 after fermentation and drying for sticks
      fermented by the starter culture (pH 4.6) and for sticks naturally fermented (pH
      5.5) were 1.96 and 0.28 log10 CFU/g, respectively. However, cooking soudjouk
      sticks produced with a starter culture and holding at 54.4 degrees C for 0, 30,
      or 60 min reduced pathogen numbers from an initial level after fermentation and
      drying of 5.69 log10 CFU/g to below a detectable level by either direct plating
      (<1.0 log10 CFU/g) or by enrichment. In contrast, cooking soudjouk sticks
      produced without an added starter culture decreased pathogen numbers from an
      initial level after fermentation and drying of 7.37 to 5.65 log10 CFU/g (54.4
      degrees C, no hold), 5.04 log10 CFU/g (54.4 degrees C, 30 min hold), and 4.67
      log10 CFU/g (54.4 degrees C, 60 min hold). In general, numbers of E. coli O157:H7
      within both groups of soudjouk sticks decreased faster during storage at 21
      degrees C compared to 4 degrees C. After 28 days of storage, total reductions in
      pathogen numbers in soudjouk sticks produced using a starter culture but that
      were not subsequently cooked were 7.65 and 3.93 log10 CFU/g at 21 and 4 degrees
      C, respectively. For naturally fermented soudjouk, total reductions varied from
      4.47 to 0.45 log10 CFU/g, depending on the cooking time and storage temperature.
      These data provide guidelines for manufacturers of dry sausage of ethnic origin,
      including soudjouk, to assess the safety of their processes for control of E.
      coli O157:H7.

PMID- 11510653
TI  - The effect of temperature and low pH on survival of Shigella flexneri in broth.
AB  - The survival characteristics of Shigella fiexneri strain 5348 were determined in
      brain heart infusion broth as a function of low pH (2 to 5) and temperature (4 to
      37 degrees C). Stationary-phase cells were inoculated into sterile media to give
      initial populations of 6 to 7 log10 CFU/ml. Bacterial populations were determined
      periodically by aerobic plate counts. Survivor curves were fitted from plate
      count data using a two-phase linear model to derive lag times and slopes of the
      curves, from which D-values and times to a 4-D (99.99%) inactivation (T4D) were
      calculated. In general, survival increased as temperature decreased and as pH
      increased. Bacterial populations reached undetectable levels (<1.3 log10 CFU/ml)
      at 37, 28, 19, 12, and 4 degrees C in media adjusted to pH 4 after 5, 15, 23, 85,
      and 85 days, respectively, and in media adjusted to pH 3 after 1, 7, 9, 16, and
      29 days, respectively. In media adjusted to pH 2, bacterial populations were
      stable for 2 to 12 h at temperatures of 19 degrees C or lower and reached
      undetectable levels after 1 to 3 days, while at 28 and 37 degrees C, the bacteria
      were undetectable after 8 and 2 h, respectively. In media adjusted to pH 5,
      bacterial levels decreased only 0.5 to 1.5 log10 CFU/ml after 75 days at 4
      degrees C and decreased to undetectable levels after 135 days at 12 degrees C,
      while growth occurred at higher temperatures. These results indicate that S.
      flexneri is acid resistant and that acidic foods may serve as vehicles for
      infection.

PMID- 11510654
TI  - A double antibody sandwich enzyme-linked immunosorbent assay for the detection of
      Salmonella using biotinylated monoclonal antibodies.
AB  - A double antibody sandwich enzyme-linked immunosorbent assay (ELISA) was
      developed using monoclonal antibodies (MAbs) as a rapid, economical alternative
      to culture isolation procedures for detection of Salmonella. Four MAbs previously
      shown to react with Salmonella strains representing 18 different serogroups were
      evaluated as capture antibodies and, after biotinylation, as detection
      antibodies. One MAb (M183) was selected for use in the ELISA to capture and
      detect Salmonella antigens. The detection limit of the ELISA was evaluated using
      Salmonella enterica subspecies enterica serovar Typhimurium and various selective
      and nonselective Salmonella enrichment media. The highest detection limit (ca.
      10(4) CFU/ml) was achieved using an enrichment broth containing brain heart
      infusion, yeast extract, sodium hydrogen selenite, and sodium cholate (BYSC)
      after preenrichment in buffered peptone water. The ELISA detected all Salmonella
      serovars tested, which included representative serovars of serogroups B, C, D,
      and E and gave negative results for all non-Salmonella species tested. Samples
      (106) from various sources, including fecal samples from humans and pigeons,
      chicken carcass rinses, chicken parts, feed, and the environment, were used to
      evaluate the performance of the ELISA. The ELISA had a specificity and
      sensitivity of 100 and 91%, respectively, and a kappa value of 0.93 relative to
      the culture methods. Such an ELISA has the potential to be used in the
      implementation of the pathogen reduction and hazard analysis critical control
      point systems as well as in clinical laboratories.

PMID- 11510655
TI  - Heterogeneity of environmental, retail, and clinical isolates of Vibrio
      vulnificus as determined by lipopolysaccharide-specific monoclonal antibodies.
AB  - The opportunistic pathogen Vibrio vulnificus expresses lipopolysaccharide (LPS)
      antigens on its outer membrane surface. A serological typing system was developed
      for these antigens, utilizing the discriminatory recognition of monoclonal
      antibodies (MAb) by ELISA. MAb were used to recognize five unique types of LPS
      associated antigens for examination of clinical. environmental, and retail
      isolates of V. vulnificus. The overall serotype profile of the clinical isolates
      was significantly different (P < 0.05) from that of the environmental and retail
      isolates. A higher percentage of clinical isolates were typable (61%) compared to
      the environmental isolates (41%) and retail isolates (44%). In particular, the
      percentage of serotype 1/5 among clinical isolates (33%), compared to that of
      environmental (9%) and retail (4%), was highly significant (P < 0.0001). Among
      the environmental Gulf Coast isolates, there were differences in the prevalence
      of serotypes 2 and 3 (P < 0.05), depending on whether isolates were obtained from
      Louisiana or Alabama harvest sites. There were no statistically significant
      differences between the serotype profiles of Gulf and Atlantic Coast retail
      isolates despite the absence of serotype 1/5 from the Atlantic Coast. While some
      serotype diversity was detected in V. vulnificus isolated during different
      seasons, from different geographic locations, and at retail versus at harvest,
      there was no apparent concordance between any of the serotype distributions
      obtained from oysters versus that isolated clinically. The heterogeneity of
      environmental isolates and relative homogeneity among clinical isolates suggest
      that human risk may not be predicted on quantitative exposure alone.

PMID- 11510656
TI  - Influence of surface finish on the cleanability of stainless steel.
AB  - Stainless steel for fabricating food processing equipment is available with
      various surface finishes. The objective of this research was to determine the
      effect of surface finish on cleanability. Nine samples of stainless steel, type
      304, from various manufacturers including no finish (hot rolled and pickled), #4
      finish, 2B mechanical polished, and electropolished were tested. Cleanability was
      assessed by using coupon samples soiled with either cultured milk inoculated with
      spores of Bacillus stearothermophilus or by growth of a Pseudomonas sp. biofilm.
      Samples were cleaned by immersion in a turbulent bath of 1.28% sodium hydroxide
      at 66 degrees C for 3 min followed by a sterile water rinse, neutralizing in 0.1%
      phosphoric acid for 30 s, rinsing in phosphate buffer, sanitizing in 100 ppm
      hypochlorite, neutralizing in sodium thiosulfate, and drying. To determine
      residual milk soil, coupon samples were covered with PM indicator agar and
      incubated for 25 h at 58 degrees C. Other coupons were subjected to an additional
      10 soiling or cleaning cycles, and the residual protein was measured by using
      epifluorescent microscopy and image analysis. Results indicate that the spore
      count was more precise for measuring initial cleanability of the finished
      samples, and the protein residue determination was useful for determining the
      effect of repeated cleaning. Data on the removal of milk soil suggest that
      stainless steel should be purchased based on measures of surface defects rather
      than finish type. Surface defects, as determined using a surface roughness gauge,
      produced a correlation of 0.82 with spore counts. Data also indicated that
      biofilm was more difficult to remove than milk-based soil.

PMID- 11510657
TI  - The effect of nanometer dimension topographical features on the hygienic status
      of stainless steel.
AB  - Wear of food contact surfaces through abrasion may increase the surface roughness
      and introduce different topographical features. Both of these properties may
      enhance retention of soil and microorganisms and affect the surface cleanability.
      To test this hypothesis, stainless steel surfaces with topographical features and
      surface roughness (Ra) values simulating those of worn in-use surfaces were
      prepared. Surfaces were imaged and Ra values determined using atomic force
      microscopy (AFM). These ranged from 23 to 900 nm. Surfaces were sprayed with
      standardized cell suspensions of Pseudomonas aeruginosa or Staphylococcus aureus
      and allowed to air dry and were then cleaned using a nonionic detergent delivered
      via a manual linear cleaning device. There was a 2-log reduction in numbers
      attached after cleaning, but there was no significant difference (P > 0.05)
      between the cleanability of the surfaces in terms of the numbers of cells per
      unit area remaining after cleaning, although cells appeared to be retained within
      topographical features. Thus, the simulated effect of wear of a hygienic food
      contact surface did not affect its cleanability after a one-off microbiological
      soiling event. AFM provided hitherto unavailable information on the topography of
      worn stainless steel surfaces. In future work, the surfaces will be repeatedly
      challenged with an organic soil-microorganism mixture after cleaning events, to
      provide a more rigorous, realistic test.

PMID- 11510658
TI  - Pathogen testing of ready-to-eat meat and poultry products collected at federally
      inspected establishments in the United States, 1990 to 1999.
AB  - The Food Safety and Inspection Service (FSIS) conducted microbiological testing
      programs for ready-to-eat (RTE) meat and poultry products produced at
      approximately 1,800 federally inspected establishments. All samples were
      collected at production facilities and not at retail. We report results here for
      the years 1990 through 1999. Prevalence data for Salmonella, Listeria
      monocytogenes, Escherichia coli O157:H7, or staphylococcal enterotoxins in nine
      different categories of RTE meat and poultry products are presented and
      discussed. The prevalence data have certain limitations that restrict statistical
      inferences, because these RTE product-testing programs are strictly regulatory in
      nature and not statistically designed. The cumulative 10-year Salmonella
      prevalences were as follows: jerky, 0.31%; cooked, uncured poultry products,
      0.10%; large-diameter cooked sausages, 0.07%; small-diameter cooked sausages,
      0.20%; cooked beef, roast beef, and cooked corned beef, 0.22%; salads, spreads,
      and pates, 0.05%; and sliced ham and luncheon meat, 0.22%. The cumulative 3-year
      Salmonella prevalence for dry and semidry fermented sausages was 1.43%. The
      cumulative 10-year L. monocytogenes prevalences were as follows: jerky, 0.52%;
      cooked, uncured poultry products, 2.12%; large-diameter cooked sausages, 1.31%;
      small-diameter cooked sausages, 3.56%; cooked beef, roast beef, and cooked corned
      beef, 3.09%; salads, spreads, and pates, 3.03%; and sliced ham and luncheon meat,
      5.16%. The cumulative 3-year L. monocytogenes prevalence for dry and semidry
      fermented sausages was 3.25%. None of the RTE products tested for E. coli O157:H7
      or staphylococcal enterotoxins was positive. Although FSIS and the industry have
      made progress in reducing pathogens in these products, additional efforts are
      ongoing to continually improve the safety of all RTE meat and poultry products
      manufactured in federally inspected establishments in the United States.

PMID- 11510659
TI  - Home-style beef jerky: effect of four preparation methods on consumer
      acceptability and pathogen inactivation.
AB  - The safety of homemade jerky continues to be questioned. Producing a safe product
      that retains acceptable quality attributes is important. Lethality of Salmonella,
      Escherichia coli O157:H7, and Listeria monocytogenes as well as consumer
      acceptability and sensory attributes of jerky prepared by four methods were
      examined. Preparation methods were drying marinated strips at 60 degrees C
      (representing a traditional method), boiling strips in marinade or heating in an
      oven to 71 degrees C prior to drying, and heating strips in an oven after drying
      to 71 degrees C. A 60-member consumer panel rated overall acceptability. A 10
      member descriptive panel evaluated quality attributes. Samples heated after
      drying and samples boiled in marinade prior to drying had slightly higher
      acceptability scores but were not statistically different from traditional
      samples. Although the four treatments were significantly different in color (P =
      0.0001), saltiness (P = 0.0001), and texture (P = 0.0324), only texture appeared
      to influence overall consumer acceptability. Microbial challenge studies
      subjecting the pathogens to the four treatments showed a 5.8-, 3.9-, and 4.6-log
      reduction of E. coli O157:H7, L. monocytogenes, and Salmonella, respectively,
      even with traditional drying. Oven treatment of strips after drying was shown to
      have the potential to reduce pathogen populations further by approximately 2
      logs. In conclusion, a safer, yet acceptable home-dried beef jerky product can be
      produced by oven-heating jerky strips after drying.

PMID- 11510660
TI  - Acid phosphatase activity and color changes in consumer-style griddle-cooked
      ground beef patties.
AB  - The U.S. Department of Agriculture and the Food and Drug Administration have
      issued temperature requirements to help consumers cook beef patty products that
      are free of pathogens. Verification of end-point temperature (EPT) is needed in
      cooked meat products due to concerns over outbreaks of Escherichia coli O157:H7.
      Acid phosphatase (ACP) activity was studied as a potential method for
      determination of EPT in ground beef patties cooked nonfrozen, patties frozen 7
      days and thawed at room temperature 4 h in a refrigerator or by microwave, and
      patties made from ground beef frozen in store packages, then thawed in a
      refrigerator overnight. Pressed-out meat juices were analyzed from patties (n =
      314) cooked to 57.2 degrees C (135 degrees F). 65.6 degrees C (150 degrees F),
      71.1 degrees C (160 degrees F), and 79.4 degrees C (175 degrees F) target EPTs.
      Expressed meat juice and internal meat patty color decreased in redness as EPT
      increased. Freezing whole packs with slow refrigerator or room temperature
      thawing caused significantly greater loss of redness in expressed cooked meat
      juice than did other handling methods. Log10 ACP had a significant linear (R2 =
      0.99) response to EPT. Results show that the 3- to 5-min ACP test could be used
      to verify EPT in griddle-cooked hamburger patties.

PMID- 11510661
TI  - The effect of nisin on the physiology of Bifidobacterium thermophilum.
AB  - The effects of nisin on lactate accumulation, growth, and Fe(III) binding by
      Bifidobacterium thermophilum (ATCC 25866) and Bifidobacterium breve (ATCC 15700)
      were investigated. Nisin inhibited lactate production by B. thermophilum at
      concentrations of less than 1 microg/ml, but this effect could be largely
      eliminated by pretreatment of the organism with 100 to 400 microM Al(III) or
      La(III). Nisin also inhibited the growth of B. thermophilum at concentrations of
      2 to 3 microg/ml, with lower concentrations showing lag periods and/or slower
      rates of growth. However, Al(III) could not negate these effects, most likely
      because of Al(III) chelation by the trypticase-proteose-yeast extract medium.
      Nisin was able to increase instantaneous Fe(III) binding by both B. thermophilum
      and B. breve, though prolonged-time experiments (up to 120 min) with B.
      thermophilum indicated no difference in total Fe(III) bound. Nisin was thus able
      to increase the free radical reaction rate with bifidobacteria and the resultant
      rate of Fe(III) binding. It was concluded that nisin will normally inhibit the
      metabolic activity of B. thermophilum along with that of certain bacterial
      pathogens; however, this effect may in some instances, be abated by a
      pretreatment with Al(III). Moreover, by accelerating free radical action and the
      binding of iron by bifidobacteria, nisin may be able to potentiate their normal
      probiotic action.

PMID- 11510662
TI  - Occurrence of false-positive results of inhibitor on milk samples using the
      Delvotest SP assay.
AB  - Three hundred twenty-one quarter, 207 whole udder, 310 bulk tank, and 93 tank
      lorry milk samples were examined for confirmation of the presence of inhibitor by
      Delvotest SP assay. Four hundred twenty-six Holstein cows of no drug treatment
      for at least 30 days from January 1998 to September 1999 were used. Reading time
      was 2.50, 2.75, and 3.00 h, and results of sampling were recorded by four types
      according to comparison with the color of the well containing the control milk
      sample. False-positive outcome was identified by Delvotest SP assay in quarter
      (13 of 321), whole udder (9 of 207), and bulk tank milk samples (4 of 310), but
      was not shown on tank-lorry milk samples (0 of 93) at the reading time of 2.50 h.
      All of the 26 false-positive samples were negative from the examination after
      heat treatment at 82 degrees C for 5 min. But, two bulk tank milk samples that
      appeared to have positive results in LacTek and Charm II tests were positive from
      the test following heat treatment. Somatic cell counts (SCC) were related to the
      probability of a false-positive result. The more SCC increased, the more the
      occurrence of a false-positive result increased. In our investigations, 4 of 310
      bulk tank milk samples at the reading time of 2.50 h produced false-positive
      results, and no false-positive results were apparent at a reading time of 2.75 h.
      Also, the occurrence of false-positive results in quarter and whole udder milk
      samples decreased when agar was cultured for 2.75 to 3.00 h. There were no false
      positive results from tank-lorry milk samples. These results indicate that the
      Delvotest SP assay may provide a suitable means for the detection of drug
      residues in not only quarter and whole udder milk of cows but also in bulk tank
      and tank-lorry milk following reading times of 2.75 to 3.00 h.

PMID- 11510663
TI  - Reduction of patulin during apple juice clarification.
AB  - Patulin is a mycotoxin produced by a number of molds involved in fruit spoilage.
      This compound is carcinogenic and teratogenic. Various methods are currently used
      to reduce the levels of patulin in apple juice, namely, charcoal treatment,
      chemical preservation (sulfur dioxide), gamma irradiation, fermentation, and
      trimming of fungus-infected apples. Many of these processes are expensive and
      time-consuming. Therefore, there is a need to find a convenient and economical
      process to control patulin levels. This study was undertaken to evaluate the
      effectiveness of several clarification processes for the reduction of patulin.
      Clarification was carried out on a laboratory scale. Apple pulp was spiked with
      patulin, pressed, and clarified using four different processes, namely, fining
      with bentonite, enzyme (pectinase) treatment, paper filtration, and
      centrifugation. Patulin was recovered from the clarified juice by liquid-liquid
      extraction, and solid-phase chromatography was used for sample clean-up prior to
      analysis by high-performance liquid chromatography (HPLC). The minimum detectable
      limit using HPLC was 20 microg/liter. Pressing followed by centrifugation
      resulted in an average toxin reduction of 89%. Total toxin reduction using
      filtration, enzyme treatment, and fining were 70, 73, and 77%, respectively.
      Patulin reduction was due to the binding of the toxin to solid substrates that
      was verified by analyzing the clarified juice as well as the filter cake, pellet,
      and sediment. The combined concentrations correlated to the spiked concentration.
      These results reveal that clarification was successful in the reduction of
      patulin levels in apple juice. However, clarification resulted in high levels of
      patulin in the pressed pulp after filtration and centrifugation, and this could
      be harmful if they are used as animal feeds.

PMID- 11510664
TI  - Trichothecene and moniliformin production by Fusarium species from western
      Canadian wheat.
AB  - Fusarium graminearum, Fusarium culmorum, and Fusarium avenaceum, isolated from
      Fusarium-damaged wheat harvested in western Canada, were cultured and evaluated
      for mycotoxin production. Extracts of the culture media were assayed for
      trichothecenes by gas chromatography-mass spectrometry and for moniliformin by
      liquid chromatography. Deoxynivalenol (DON) was found in 28 of 42 isolates of F.
      graminearum and 42 of 42 isolates of F. culmorum at levels ranging from 0.5 to
      25.0 microg/g. 15-AcetylDON was found in 28 of 42 isolates of F. graminearum at
      levels ranging from 1.0 to 7.1 microg/g. 3-AcetylDON was found in 41 of 42
      isolates of F. culmorum at levels ranging from 0.8 to 13.0 microg/g. Several
      other trichothecenes were assayed but not detected in the culture medium.
      Moniliformin was present in 40 of 42 isolates of F. avenaceum at levels ranging
      from 1.3 to 138.1 microg/g, but was not present in any of the isolates of F.
      graminearum or F. culmorum.

PMID- 11510665
TI  - Occurrence of ochratoxin A-producing fungi in raw Brazilian coffee.
AB  - Ochratoxin A (OA)-producing fungi were identified in coffee at different stages
      of maturation. The toxin was quantified in coffee during terrace drying and in
      coffee stored in barns. By direct plating, a high level of contamination (100%)
      was found in the coffee beans studied, with the genus Aspergillus representing
      33.2%, of which Aspergillus ochraceus and Aspergillus niger represented 10.3 and
      22.9%, respectively, of the strains isolated from the coffee beans. The capacity
      to produce ochratoxin was determined in 155 strains of A. ochraceus and A. niger
      using both the agar plug method and extraction with chloroform, giving positive
      results for 88.1% of the A. ochraceus strains and 11.5% of the A. niger strains.
      Analysis for OA in the terrace and barn coffee samples showed that, independent
      of cultivar, year harvested, or production region, all except one of the samples
      analyzed showed mycotoxin levels below the limit suggested by the European Common
      Market (8 microg/kg), thus indicating that the problem is restricted and due to
      severe faults in harvesting and storage practices.

PMID- 11510666
TI  - High-performance liquid chromatographic determination of carbadox, olaquindox,
      furazolidone, nitrofurazone, and nitrovin in feed.
AB  - A high-performance liquid chromatography with gradient programming method was
      developed to determine the amount of carbadox (CBX), olaquindox (OLQ),
      furazolidone (FZ), nitrofurazone (NF), and nitrovin (NTV) in feed simultaneously.
      Complete separation of the drugs was obtained using a C8 silica gel column with
      gradients of acetonitrile as mobile phase. The mobile phase used an acetonitrile
      gradient with an initial hold time of 1 min at 0% acetonitrile, followed by an
      increase to 50% acetonitrile over 10 min. The correlation coefficients (r) for
      calibration curves of the five feed additives were greater than 0.999. The
      relative standard deviations (RSDs) of peak areas from four injections for these
      drugs at three concentrations were less than 3.0%, although the RSD for NTV at 5
      ppm was somewhat large (6.7%). The medicated feeds were extracted by pretreating
      with water, extracted with 95% dimethylformamide overnight at room temperature,
      and cleaned up on a column of alumina oxide. Recoveries of CBX, OLQ, FZ, NF, and
      NTV from low level spiked feed were 102.0, 94.6, 97.4, 110.6, and 66.0%,
      respectively, and from high level spiked feed, they were 114.09, 99.1, 97.3,
      109.9, and 62.7%, respectively.

PMID- 11510667
TI  - Direct microscopic observation of lettuce leaf decontamination with a prototype
      fruit and vegetable washing solution and 1% NaCl-NaHCO3.
AB  - Efficacy of a prototype, food-grade alkaline surfactant washing solution and 1%
      NaCl-NaHCO3 (pH 10.0) against Escherichia coli O157:H7 cells on lettuce leaves
      was evaluated. Lettuce was inoculated with 10(9) CFU/ml of E. coli O157:H7 for 24
      +/- 1 h at 4 degrees C. Samples were rinsed and treated with the prototype
      washing solution containing lauryl sodium sulfate or NaCl-NaHCO3 for 3 min at 22
      degrees C. Viability of E. coli O157:H7 cells was examined by plate counts at the
      surface and cut edge, and by confocal scanning microscopic (CSLM) observation of
      samples stained with Sytox green and Alexa 594 conjugated antibody against E.
      coli O157:H7 at intact leaf surface, stomata, and damaged tissue (0 to 10, 30 to
      40, and 0 to 40 microm from the cut surface). Although both treatments caused
      significant log reductions in CFU at the surface and cut edge, log reductions
      were greater for the prototype washing solution (0.7 to 1.1 log CFU/cm2) than for
      NaCl-NaHCO3 (0.2 to 0.4 log CFU/cm2) (P < 0.05). Percentage of viability
      determined by CSLM for prototype washing solution was significantly greater at 30
      to 40 microm from cut surfaces than at 0 to 10 and 0 to 40 microm from cut
      surfaces and intact surfaces (P < 0.05). Stomata provided moderate protection.
      NaCl-NaHCO3 was less effective than the prototype washing solution, and high
      percentages of E. coli O157:H7 cells remained viable at all sites except at the
      surface. The percent viabilities determined by CSLM were not significantly
      different from those determined by plate counts for NaCl-NaHCO3 treatment (P >
      0.05). However, CSLM indicated significantly greater percent viability than plate
      counts for lettuce treated with the prototype washing solution (P < 0.05).
      Surfactant-containing washing solutions warrant additional testing for
      decontamination of fresh produce.

PMID- 11510668
TI  - Two processing methods for the isolation of Salmonella from naturally
      contaminated alfalfa seeds.
AB  - Two processing methods were examined for the recovery of Salmonella from
      naturally contaminated alfalfa seed. Seed samples, from each of three
      investigations, were processed by sprouting and shredding before preenrichment
      and culture. In lot A, Salmonella serotype Newport was isolated from 3 of 30
      sample units with the sprouting method and 2 of 30 with the shredding method. In
      lot B, three serotypes in various combinations were isolated from 10 of 30 sample
      units with the sprouting method and 9 of 30 with the shredding method. In lot C,
      Salmonella group C1 was isolated from 27 of 30 sample units with the sprouting
      method and 24 of 30 with the shredding method. Additionally, serotype Newport was
      found in one lot C sample unit. Using shredded seed data, a most probable number
      (MPN) for Salmonella contamination per lot was calculated. Serotype Newport was
      estimated at 0.07 MPN/100 g in lot A; the concentration for three serotypes was
      estimated to be 0.36 MPN/100 g in lot B; Salmonella group C1 was estimated at 1.8
      MPN/100 g in lot C. Our success in isolating Salmonella from alfalfa seeds was
      likely attributed to the volume of material tested and the quick acquisition of
      the seeds after the outbreak was identified. Shredding the seeds was easier and
      yielded definitive results more quickly than sprouting.

PMID- 11510669
TI  - Ascorbic acid enhances destruction of Escherichia coli O157:H7 during home-type
      drying of apple slices.
AB  - Destruction of Escherichia coli O157:H7 was evaluated on inoculated apple slices
      dehydrated at two temperatures with and without application of predrying
      treatments. Half-ring slices (0.6 cm thick) of peeled and cored Gala apples were
      inoculated by immersion for 30 min in a four-strain composite inoculum of E. coli
      O157:H7. The inoculated slices (8.7 to 9.4 log CFU/g) either received no
      predrying treatment (control), were soaked for 15 min in a 3.4% ascorbic acid
      solution, or were steam blanched for 3 min at 88 degrees C immediately prior to
      drying at 57.2 or 62.8 degrees C for up to 6 h. Samples were plated on tryptic
      soy (TSA) and sorbitol MacConkey (SMAC) agar media for direct enumeration of
      surviving bacterial populations. Steam blanching changed initial inoculation
      levels by +0.3 to -0.7 log CFU/g, while immersion in the ascorbic acid solution
      reduced the inoculation levels by 1.4 to 1.6 log CFU/g. Dehydration of control
      samples for 6 h reduced mean bacterial populations by 2.9 log CFU/g (TSA or SMAC)
      at 57.2 degrees C and by 3.3 (SMAC) and 3.5 (TSA) log CFU/g at 62.8 degrees C.
      Mean decreases from initial inoculum levels for steam-blanched slices after 6 h
      of drying were 2.1 (SMAC) and 2.0 (TSA) log CFU/g at 57.2 degrees C, and 3.6 (TSA
      or SMAC) log CFU/g at 62.8 degrees C. In contrast, initial bacterial populations
      on ascorbic acid-pretreated apple slices declined by 5.0 (SMAC) and 5.1 (TSA) log
      CFU/g after 3 h of dehydration at 57.2 degrees C, and by 7.3 (SMAC) and 6.9 (TSA)
      log CFU/g after 3 h at 62.8 degrees C. Reductions on slices treated with ascorbic
      acid were in the range of 8.0 to 8.3 log CFU/g after 6 h of drying, irrespective
      of drying temperature or agar medium used. The results of immersing apple slices
      in a 3.4% ascorbic acid solution for 15 min prior to drying indicate that a
      predrying treatment enhances the destruction of E. coli O157:H7 on home-dried
      apple products.

PMID- 11510670
TI  - Microbiological condition of ground meat retailed in Monterrey, Mexico.
AB  - Eighty-eight samples of ground meat were randomly collected from retail stores in
      the metropolitan area of Monterrey, Mexico, and were analyzed for microbial
      contamination. Methods were those recommended by the Mexican regulation and/or
      the U.S. Food and Drug Administration. Over 75% of the samples contained > 10(5)
      total mesophilic microorganisms per g, and over 40% had >10(6) total coliforms
      per g. Fecal coliforms were present in most samples. Staphylococcus aureus was
      detected in 2.3% of the samples, Salmonella spp. in 11.4%, Listeria spp. in 62%,
      and L. monocytogenes in 16%. Escherichia coli was detected in 76% of samples, but
      none was serotype O157:H7. Shigella spp. was not found in any sample. Fusarium
      spp. and Mucor spp. were detected in 3.4% of the samples, and low levels of yeast
      in 93%. The microbiological quality of the ground meat analyzed was
      unsatisfactory, and the product could be an important cause of food poisoning.

PMID- 11510671
TI  - Occurrence of anaerobic bacterial, clostridial, and Clostridium perfringens
      spores in raw goose livers from a poultry processing plant in Hungary.
AB  - Anaerobic bacterial, clostridial, and Clostridium perfringens spores were
      enumerated in raw goose liver samples taken after evisceration of the birds (EB)
      in the slaughterhouse and after removal of blood vessels from the liver (RBVL) in
      the cannery. The samples taken after RBVL had significantly higher (P < 0.05)
      spore counts than did those taken after EB, indicating contamination of livers
      during processing. The number of C. perfringens spores was one log cycle higher
      in the samples taken after RBVL than in those taken after EB (P < 0.05). The
      confirmation of C. perfringens according to the profiles of Rapid ID 32 A tests
      was carried out by means of the ATB Plus computer program. With an identification
      percentage of 99.9 and a T-value of 0.65, the suspect colonies proved to be C.
      perfringens. Therefore, the importance of an appropriate cleaning and sanitation
      program and of personnel hygiene should be emphasized in the industry.

PMID- 11510672
TI  - Antibacterial activity in extracts of Camellia japonica L. petals and its
      application to a model food system.
AB  - The potential presence of naturally occurring antimicrobials in petals of
      Camellia japonica L., a member of the tea family, was investigated against
      foodborne pathogens in microbiological media and food. Petals of the camellia
      flower (C. japonica L.) were extracted with methanol and fractionated into basic,
      acidic, and neutral fractions. The acidic fraction (equivalent to 1.0 g of raw
      sample per disk) produced an inhibitory zone of 14 to 19 mm (diameter) in a disk
      assay against the pathogens Salmonella Typhimurium DT104, Escherichia coli
      O157:H7, Listeria monocytogenes, and Staphylococcus aureus on agar plates. Silica
      gel adsorption column chromatography, Sephadex LH-20 column chromatography, and
      preparative purification by high-pressure liquid chromatography were used to
      purify compounds in the fraction. The mass spectrum of the antibacterial compound
      isolated had a molecular ion (M+) of m/z 116 and showed good conformity with the
      spectrum of fumaric acid (HOOC-CH=CH-COOH). An aqueous extract from the petals of
      C. japonica L. had an inhibitory effect on growth of all pathogens at 37 degrees
      C in microbiological media by increasing the lag phase. None of the
      microorganisms was inhibited completely. Milk was used as a model food system.
      Aqueous extract at a concentration of 100 mg/ml was bacteriostatic against all
      the foodborne pathogens in the milk stored at 25 degrees C for up to 4 days.

PMID- 11510673
TI  - Complaints of foodborne illness in San Francisco, California, 1998.
AB  - Foodborne diseases are an important public problem affecting millions of
      Americans each year and resulting in substantial morbidity and mortality. Many
      foodborne infections occur in outbreak settings. Outbreaks are often detected by
      complaints from the public to health authorities. This report reviews complaints
      received by the San Francisco Department of Public Health involving suspected
      foodborne illness in 1998. Although such foodborne complaints are commonly
      received by health officials, we provide the first review of population-based
      data describing such complaints. We use a broad definition of a foodborne disease
      outbreak. We judged a complaint to be a "likely foodborne disease outbreak" if it
      involved more than one person and more than one family; no other common meals
      were shared recently by ill persons; diarrhea, vomiting, or both was reported;
      and the incubation period was more than one hour. In 1998, 326 complaints of
      foodborne illness, involving a total of 599 ill people, were received by the
      Communicable Disease Control Unit in San Francisco. The complaints involved from
      1 to 36 ill persons, with 61% involving one ill person and 25% involving two ill
      persons. Of the 126 reports involving illness in more than one person, 77 (61%)
      were judged to be likely foodborne disease outbreaks. Three of these 77 outbreaks
      had been investigated prior to our review. This project confirms that more
      foodborne disease outbreaks occur than are reported to state and national
      outbreak surveillance systems. Our review of the San Francisco system highlights
      opportunities for gleaning valuable information from the foodborne disease
      complaint systems in place in most jurisdictions.

PMID- 11510674
TI  - Evaluation of buffalo colostrum quality by estimation of enzyme activity levels.
AB  - A study to evaluate the value and potential use of colostral enzymes as markers
      for the evaluation of buffalo colostrum quality was conducted. The enzymes gamma
      glutamyltransferase (GGT), lactic dehydrogenase (LDH), and alkaline phosphatase
      (ALP) in buffalo's colostrum were measured spectrophotometrically, and their
      activities were correlated with the gamma-globulin content. Gamma-globulin
      concentration was determined following the electrophoretic separation of the
      colostral proteins and quantified with a densitometer. Colostrum was obtained
      from 15 dams, soon after calving. Means, standard deviations, correlation
      coefficients, and degree of significance were calculated using the general linear
      model procedure of the Statistical Analysis Systems program. The activity of GGT
      in the colostrum was the highest, followed by LDH and ALP. A significant
      correlation (r = 0.86; P < 0.001) was seen between GGT and gamma-globulin
      concentration in the colostrum, supporting the suggestion of using this enzyme as
      a marker for the evaluation of colostrum quality.

PMID- 11510675
TI  - Fumonisins B1 and B2 in black tea and medicinal plants.
AB  - Fumonisins are mycotoxins produced by Fusarium moniliforme that are prevalent in
      cereals and other agricultural products. These mycotoxins have been pointed to as
      a natural cause of equine leukoencephalomalacia, porcine pulmonary edema, and
      human esophageal cancer. A total of 87 samples, 18 black tea samples and 69
      samples of four different medicinal plants (chamomile, leaves of the orange tree,
      leaves and flowers of the linden tree, and corn silk), for infusions preparations
      were acquired from supermarkets in Lisbon, Portugal. The samples were analyzed
      for the incidence and levels of fumonisin B1 (FB1) and fumonisin B2 (FB2) by high
      performance liquid chromatography. The detection limit was 20 microg/kg for both
      FB1 and FB2. FB1 was detected in 55 (65.5%) of the 87 samples. The highest number
      of positive samples was found in black tea (88.8%). with levels ranging from 80
      to 280 microg/kg. Relative to the medicinal plants, the leaves of the orange tree
      had higher concentrations of FB1 (range, 350 to 700 microg/kg) followed by leaves
      and flowers of the linden tree (range, 20 to 200 microg/kg). The samples of corn
      silk and chamomile had less contamination of FB1, with concentrations ranging
      from 50 to 150 microg/kg and 20 to 70 microg/kg, respectively. None of the
      samples tested had contamination of FB2. This is the first report of the natural
      occurrence of fumonisins in black tea and medicinal plants in Portugal. We
      reinforce the necessity to implement risk management measures for safety control
      of this kind of product.

PMID- 11510676
TI  - Novel Plasmodium falciparum clones and rising clone multiplicities are associated
      with the increase in malaria morbidity in Ghanaian children during the transition
      into the high transmission season.
AB  - A survey of Plasmodium falciparum infection and clone multiplicity in Ghanaian
      children was carried out to study the effect of the onset of the malaria
      transmission season on disease incidence. Fortnightly blood samples were
      collected from 40 children living in the rural town of Dodowa, between February
      and August 1998. P. falciparum parasite densities were calculated and PCR
      genotyping was carried out using the polymorphic MSP-1 and MSP-2 genes as target
      loci for the estimation of the number of parasite clones in each sample. The
      average clone number was estimated using maximum likelihood techniques and the
      minimum number of clones per patient was analysed for the effects of age, sex,
      season, minimum number of clones per child, level of parasitaemia and parasite
      genotype. The statistical analysis indicated that the more clones a child
      carried, the more likely they were to have a clinical malaria episode. This was
      true after adjusting for age and season effects and for the measured circulating
      parasitaemia. The probability of clinical disease also increased if the MSP-1 MAD
      20 and the MSP-2 FC 27 alleles were present. This longitudinal analysis thus
      indicates that the probability of a Ghanaian child having a symptomatic malaria
      episode is positively associated with both increasing numbers and novel types of
      P. falciparum clones.

PMID- 11510677
TI  - Phagocytosis of malarial pigment haemozoin by human monocytes: a confocal
      microscopy study.
AB  - Haem from host erythrocyte (RBC) haemoglobin is polymerized in the digestive
      organelle of Plasmodium falciparum to haemozoin (HZ), a crystaLline, insoluble
      substance. Human monocytes avidly ingest HZ that persists undigested for long
      periods of time, and generates potent bioactive lipid peroxide derivatives.
      Protein kinase C, an effector of signal transduction, phagolysosome formation and
      acidification, is inhibited in HZ-fed monocytes. Inability to digest HZ might
      derive from impairment in phagolysosome formation or acidification. Time-course
      and extent of HZ phagocytosis and acidification of phagolysosomes were studied by
      quantitative confocal microscopy. From 180 min until 72 h after the start of
      phagocytosis approximately 75-79% of the monocytes contained massive amounts of
      HZ. Coincidence between red (HZ) and green (acidic organelles) fluorescent
      compartments was very high. Confocal images showed that at 30-60 min after the
      start of phagocytosis, HZ was preferentially present as separated particles, with
      full co-localization of red and green fluorescence. Later on HZ-laden
      phagolysosomes tended to fuse together. In conclusion, phagolysosome formation
      and acidification were normal in HZ-fed monocytes during the 72-h observation
      time. The presence of HZ in the phagolysosome, the site of antigen processing,
      may offer a physical link with immunodepression in malaria.

PMID- 11510678
TI  - Coccidiosis in the European badger, Meles meles in Wytham Woods: infection and
      consequences for growth and survival.
AB  - In total 1502 faecal samples were collected from a population of European badgers
      (Meles meles) between 1992 and 1995 at Wytham Woods, Oxfordshire, UK. Two
      coccidia species, Eimeria melis and Isospora melis, were identified. Cubs showed
      a marked seasonal pattern of infection with E. melis, with infection occurring at
      significantly higher intensity and prevalence than in adults. There was
      preliminary evidence to suggest that infantile coccidiosis in badgers may be
      associated with impaired growth and increased mortality.

PMID- 11510679
TI  - Parasite richness and abundance in insular and mainland feral cats: insularity or
      density?
AB  - Hosts living on islands carry few parasite species, and the prevalence and
      intensity of directly transmitted parasites are often higher in insular than in
      mainland populations. However, it is unclear whether density or other features of
      insular populations can be responsible for the pattern observed. We compared the
      parasite richness, prevalence and intensity of parasites between 2 feral
      populations of cats living either at low density on an island (Kerguelen) or at
      high density on the mainland (Lyon). Parasite richness was higher in Lyon than in
      Kerguelen, where only Toxocara cati was found. T. cati egg prevalence was higher
      in Kerguelen (71.1%) than in Lyon (58.0%). Because cat density cannot explain
      this pattern, we propose that the low number of parasite species, the diet and/or
      immunity of cats act to increase prevalence in Kerguelen. Moreover, prevalence,
      intensity and variance-to-mean ratio increased with age and body mass in
      Kerguelen whereas, in Lyon, prevalence decreased with age and body mass. We
      hypothesize that the pattern of exposure differs between populations, and that
      density-dependent parasite mortality is lower in Kerguelen than in Lyon. We
      discuss the consequences concerning the influence of parasites on insular host
      populations.

PMID- 11510680
TI  - The human isolate of Brachiola algerae (Phylum Microspora): development in SCID
      mice and description of its fine structure features.
AB  - Ocular, peroral, intraperitoneal, intramuscular, and subcutaneous inoculation of
      severe combined immunodeficient (SCID) mice with spores of the human isolate
      (CDC: V404) of Brachiola algerae (syn. Nosema algerae) (Phylum Microspora)
      revealed that the microsporidium develops in viscera of the immunodeficient mouse
      host, but only after the ocular administration of spores. It is hypothesized that
      the physico-chemical milieu of the conjunctiva and cornea helped to adapt the
      originally 'poikilothermic microsporidian' to the conditions within the
      homoiothermic organism. Ocular application of spores caused no clinical signs of
      disease at the application site. However, severe infection in the liver was found
      60 days after infection, manifested as hepatosplenomegaly and multifocal miliary
      necroses and granulomas containing parasites. No microsporidia were found in any
      other tissues. Transmission electron microscopy revealed characteristic
      tubulovesicular 'secretory materials' on the plasma membrane of all developmental
      stages of B. algerae except sporoblasts and spores. These formations increase the
      parasite surface and allow more efficient metabolic communication of the parasite
      with the host cell. It is hypothesized that the presence of these structures is a
      factor helping the parasite to grow in a variety of hosts and tissues.
      Ultrastructural characters support the likelihood that B. algerae and B.
      vesicularum are conspecific, and that there exists a relationship between species
      of the genera Brachiola and Anncaliia.

PMID- 11510681
TI  - Horizontal and vertical transmission of mouse class I MHC sequence in Schistosoma
      mansoni.
AB  - The mouse major histocompatibility complex (MHC) class I sequence was detected in
      8-week-old Schistosoma mansoni by in situ polymerase chain reaction (in situ
      PCR). The signals to the mouse class I MHC sequence were observed in the nuclei
      of the mesenchymal and reproductive cells of S. mansoni. Signals were also
      observed in the cytoplasm of the tegumental tubercles. This finding suggested the
      possibility of MHC gene transfer from the host to schistosomes. Furthermore, the
      class I MHC sequence was detected in the DNA extracted from the cercariae of S.
      mansoni by nested PCR. Neither the nucleotide sequence of class I MHC detected in
      adult worm DNA nor that of class I MHC detected in the host (mouse) DNA was
      identical with that of class I MHC detected in the cercarial DNA. From the data
      we assumed that S. mansoni may have retained their own mouse class I MHC sequence
      in their genome throughout their life-cycle.

PMID- 11510682
TI  - Morphometric correlates of host specificity in Dactylogyrus species (Monogenea)
      parasites of European Cyprinid fish.
AB  - We test the hypothesis that living on larger fish may impose constraints, i.e.
      the need to develop large attachment organs, related to the necessity to remain
      attached on large gills. For this, we compiled data on body size and morphometric
      measurements of attachment organs of 44 Dactylogyrus species (ectoparasites with
      direct life-cycle) from 19 cyprinid species. Nineteen dactylogyrid species were
      considered as specialists (infecting only 1 host species) and 25 as generalists
      (infecting more than 1 species). The lack of phylogenetic information lead us to
      perform comparative analyses using raw values and independent contrasts obtained
      by random phylogenies. Our results show that rich parasite communities are formed
      by specialists and generalists whereas poor communities are composed mainly of
      generalist parasites. Moreover, specialists are found on larger hosts, which may
      reflect a specialization on a predictable resource, as larger fish live longer
      and offer large gills for parasite colonization. Parasite specialization is shown
      to be linked with adaptation of attachment organs to their fish hosts. Two
      morphometric variables of the attachment organ, the total length of anchor and
      length of base of anchor, were positively correlated with host length for
      specialists.

PMID- 11510683
TI  - Induction of stress by the swimbladder nematode Anguillicola crassus in European
      eels, Anguilla anguilla, after repeated experimental infection.
AB  - The purpose of this study was to determine under laboratory conditions over a
      period of 311 days if infection with the nematode Anguillicola crassus induces
      stress in European eels (Anguilla anguilla), and stimulates the endocrine stress
      axis as measured by serum cortisol levels. Eels were experimentally infected with
      3rd-stage larvae (L3) in different doses to simulate natural conditions with
      varying infection pressures. Blood samples were drawn from the caudal vein every
      2 weeks and serum cortisol concentrations were determined by radioimmunoassay
      (RIA). The results showed that the application of L3 resulted in a significant
      increase in the cortisol levels. The period of time at which elevated cortisol
      values were observed was consistent with the time of larval development and the
      appearance of adult A. crassus. Thus, there is a stress response to the larval
      and young adult stages, but no chronic response to older adults. Therefore, it is
      likely that infection of eels under natural conditions especially with a high
      number of larvae may be a considerable stressor, in combination with different
      environmental factors like water temperature, pH, oxygen concentration, pollution
      and interindividual relationships.

PMID- 11510684
TI  - Eel parasite diversity and intermediate host abundance in the River Rhine,
      Germany.
AB  - European eels (Anguilla anguilla) from 2 sampling sites on the Rhine river (near
      Karlsruhe and near Worms) were investigated with respect to their parasite
      communities. Nine different metazoan species were found to live in and on the
      eels. The highest number of species was recorded from the intestine, which
      contained up to 6 different helminths. Among these, acanthocephalans were the
      most prevalent worms with the eel-specific parasite Paratenuisentis ambiguus as
      the dominant species of the intestinal component communities at both sites.
      Comparing the intestinal parasites from eels caught near Karlsruhe with those
      from Worms, the acanthocephalans showed a significantly lower abundance at Worms.
      A significantly lower mean number of intestinal helminth species as well as a
      significantly lower Brillouin's Index was found at Worms compared with Karlsruhe.
      This difference could be related to the abundance of the respective intermediate
      crustacean hosts. At the sampling site Worms the amphipod Corophium curvispinum
      was the dominant crustacean. Additionally, only the isopod Jaera istri and the
      amphipod Dikerogammarus villosus were found. All these crustacean species have
      only recently colonized the Rhine river system via the Main-Danube canal, built
      in the early 1990s. They are not known to act as intermediate hosts for any of
      the acanthocephalans found in the eels. The site near Karlsruhe exhibited a
      higher crustacean diversity, including Asellus aquaticus and different species of
      the genus Gammarus, which are all known intermediate hosts for the
      acanthocephalans found. Therefore, changes of eel parasite diversity can be
      correlated with the appearance of invading crustacean species (neozoans).

PMID- 11510685
TI  - A stochastic model for the aggregation of Onchocerca volvulus in nodules.
AB  - A model is presented which describes the aggregation of female Onchocerca
      volvulus in nodules and their distribution in the human population. The basic
      model is based on a single parameter, the formation probability q, which
      represents the probability with which incoming larvae form a new nodule. This
      parameter describes parasite behaviour which cannot easily be recognized in
      available data without modelling. The estimate for the average formation
      probability of muq = 0.39 suggests an attraction of the invading infective larvae
      to already existing nodules or resident worms with probability 0.61. No
      significant difference in muq was found between the forest and savanna parasite
      strains. The model can be used inversely to estimate the worm burden of persons
      from palpation data. The observed variance in the number of nodules per person
      requires the assumption of a variance-increasing mechanism which was implemented
      by heterogeneity within the host population (extended model with 2 parameters).
      Possible reasons for this heterogeneity are presented and its implications
      concerning the reproductive biology of the parasite are discussed.

PMID- 11510686
TI  - Evidence for translational selection in codon usage in Echinococcus spp.
AB  - We analysed the intragenomic variation in codon usage in Echinococcus spp. by
      correspondence analysis. This approach detected a trend among genes which was
      correlated with expression levels. Among the (presumed) highly expressed
      sequences we found an increased usage of a subset of codons, almost all of them G
      or C- ending. Since an increase in these bases at the synonymous sites is
      against the mutational bias (these genomes are slightly A+-T- rich), we conclude
      that codon usage in Echinococcus is the result of an equilibrium between
      compositional pressure and selection, the latter acting at the level of
      translation, mainly on highly expressed genes. This is the first report where
      translational selection for codon usage is detected among Platyhelminthes.

PMID- 11510687
TI  - Fructosamine concentration and resistance to natural, predominantly Teladorsagia
      circumcincta infection.
AB  - Fructosamine concentrations reflect protein status and because infection with
      Teladorsagia circumcincta can induce a relative protein deficiency, we examined
      the usefulness of fructosamine concentrations as markers of the intensity of
      infection in naturally infected lambs. Fructosamine concentration was a heritable
      trait and variation in fructosamine concerntrations was associated with
      differences in body weight, and a variety of parasitological variables; animals
      with increased fructosamine concentrations grew more quickly, had increased
      faecal egg counts in one of the three study years, had decreased pepsinogen
      concentrations and decreased IgA activity against 4th-stage larvae of T.
      circumcincta. Fructosamine concentrations were also associated with variation in
      the subsequent acquisition of nematodes and in the length of adult female T.
      circumcincta; lambs with increased fructosamine concentrations had fewer
      nematodes but the mean length of adult female T. circumcincta was longer.
      Therefore fructosamine concentrations are potentially useful indicators of the
      severity of nematode infection and may predict magnitude of subsequent infection.

PMID- 11510688
TI  - Sun Valley summary. Consensus and action items Expedition Inspiration meeting
      2000.
AB  - The fourth Expedition Inspiration conference was held March 21-23, 2000. While
      there are other conferences that concentrate on a particular facet of breast
      cancer, the design and goals of this conference are unusual. In order to maximize
      interaction of investigators and clinicians the meetings are small, invited, and
      private. The participants include both senior and junior physicians and
      scientists involved in clinical and basic research as well as clinical practice.
      The meetings serve four purposes: (i) Active discussion among participants who do
      not usually interact, (ii) Develop consensus as to the state of our knowledge as
      well as an action plan to stimulate future studies, (iii) Develop collaborative
      projects among the meeting participants, (iv) Foster new investigations by
      participants as well as others. This year immunology and the role of lymph nodes
      in breast cancer were the subject of the discussion. Investigators studying
      breast cancer biology, tumor immunity, potential cancer vaccines, and
      immunotherapy discussed potential therapeutic manipulation of the immune response
      to alter the natural history of breast cancer. Regional lymph nodes, the site of
      the immune response, are often affected early in the spread of breast cancer. For
      clinicians this involvement is central to planning effective treatment. The
      paradox that despite the involvement of these lymph nodes in mounting an immune
      response they are frequently the first site of breast cancer spread stimulated a
      great deal of discussion and some potentially interesting studies. The following
      consensus statement is the product of those discussions.

PMID- 11510689
TI  - Wild type p73 overexpression and high-grade malignancy in breast cancer.
AB  - The overexpression of wild type p73 is the most frequent alteration of p73 in
      malignancies. We investigated, in 70 breast carcinomas, p73 mRNA expression and
      its relationship to p53 mutations, determined by an immunohistochemical method,
      and loss heterozygosity (LOH) status of the 1p36 region, together with its
      possible implication in the pathogenesis of breast carcinomas. LOH, amplifying
      DNA by PCR using 5 markers, of 1p36 region (one intragenic to p73 gene) was found
      in 17% of cases but no significant correlation was observed with p73
      overexpression. p53 positive immunostaining was present in 33% of breast
      carcinomas, and these exhibited a statistically significant relation with p73
      overexpressed tumors. Overexpression of p73 mRNA was observed in 19 tumors (27%).
      The analysis of cases with p73 overexpression and cases with normal mRNA
      expression, in terms of age and pathologic characteristics of the tumors showed a
      significant association of p73 overexpression and tumors with lymph node
      metastases, vascular invasion and higher pathologic stage. These results suggest
      that p73 overexpression is a molecular alteration that could be implicated in the
      tumorigenesis of breast carcinomas and, eventually, in a poor clinical behavior.

PMID- 11510690
TI  - Letrozole as primary medical therapy for locally advanced and large operable
      breast cancer.
AB  - AIMS: To investigate the efficacy of letrozole 2.5 mg and 10 mg used as primary
      neoadjuvant therapy for patients with locally advanced and large operable breast
      cancer. PATIENTS AND METHODS: Twenty-four postmenopausal patients with locally
      advanced or large operable breast cancer were treated in two consecutive series
      with letrozole 2.5 mg (n = 12) or letrozole 10 mg (n = 12). Response at three
      months was measured by change in tumor volume according to WHO criteria (partial
      response was defined as a reduction in tumor volume > or = 65%). Tumor volumes
      were assessed clinically, by ultrasound and mammography, and pathologically.
      RESULTS: All 24 patients were estrogen receptor-positive, were considered
      'receptor-rich', and mean age was 77.6 years and 71.6 years in the letrozole 2.5
      mg and 10 mg treatment groups, respectively. There were five complete clinical
      responses and seven partial clinical responses in the patients treated with 2.5
      mg letrozole, and nine partial responses and three patients with stable disease
      in patients treated with 10 mg letrozole. Assessed by ultrasound and mammography,
      the 12 patients treated with 2.5 mg had one complete response, nine partial
      responses and two with no change. In the 12 patients treated with 10 mg
      letrozole, imaging gave eight partial responses and four with no change. One
      patient treated with the 2.5 mg dose had a complete clinical and pathological
      response. There was no significant difference between the two doses in effect on
      tumor volume, and no recordable side effects associated with either dose.
      CONCLUSION: Letrozole used in a neoadjuvant setting is highly effective,
      producing clinically beneficial reductions in tumor volume allowing all patients
      to have breast conserving surgery, and has an acceptable safety profile.

PMID- 11510691
TI  - Expression of growth factors, growth factor receptors and apoptosis related
      proteins in invasive breast cancer: relation to apoptotic rate.
AB  - PURPOSE: To assess the relation between growth factors, growth-factor receptors,
      p53, bcl-2 and bax expression, and the rate of apoptosis in invasive breast
      cancer patients. MATERIALS AND METHODS: Tumors from 45 patients were assessed by
      immunohistochemistry for expression patterns of five growth factors and their
      receptors; platelet-derived growth factor A chain (PDGF-AA) and PDGF-receptor
      alpha (PDGFalphaR), PDGF-BB and PDGFbetaR, transforming growth-factor alpha
      (TGFalpha) and its receptor-epidermal growth factor receptor (EGFR) and vascular
      endothelial growth factor (VEGF) and its receptors vascular-endothelial growth
      factor receptor I (FLT-1) and vascular-endothelial growth factor receptor II (FLK
      1/KDR), two growth-inhibiting factors; transforming-growth factor beta I
      (TGFbeta1) and TGFbeta2 and their receptor couple TGFbeta receptor I (TGFbetaR-I)
      and TGFbetaR-II, and basic-fibroblast growth factor (bFGF). Besides, the
      expression patterns of the bcl-2, bax and p53 gene products were investigated.
      Expression patterns were correlated to the number of apoptotic cells assessed by
      light microscopy. RESULTS: PDGF-BB and bFGF showed a positive correlation with
      the AI (p = 0.006 and p = 0.030, respectively). EGFR expression was associated
      with a high number of apoptotic cells but did not reach significance (p = 0.10).
      None of the other individual growth factors, growth-inhibiting factors or
      receptors showed a significant relation with the AI. The presence of a possible
      auto- or paracrine loop of the TGFalpha/EGFR combination was associated with a
      high number of apoptotic cells but did not reach significance (p = 0.20). PDGF
      AA, bFGF and EGFR expression showed a significant relation to p53 overexpression.
      TGFbeta2 expression showed an inverse correlation with p53 overexpression.
      CONCLUSION: We found an association between several growth factors and growth
      factor receptors with number of apoptotic cells. This underlines the importance
      of growth factors and their receptors not just in proliferation, but also,
      directly and/or indirectly, in regulating the rate of apoptosis in invasive
      breast cancer. Growth factors and their receptors may therefore be useful as
      targets of anti-cancer therapy by inducing apoptosis or increasing the
      sensitivity of cells for chemo- or hormonal therapy induced apoptosis.

PMID- 11510692
TI  - An assessment of delays in obtaining definitive breast cancer treatment in
      Southern Italy.
AB  - Female population is medically underserved in Southern Italy (in comparison with
      other Italian regions). In a recent systematic review of published studies,
      delays of 3-6 months between symptom onset and treatment have been clearly
      associated with lower survival rates for breast cancer patients. The aim of this
      study was to examine breast cancer delays in medically underserved patients in
      Southern Italy, in order to recognize their determinating factors so as to
      provide women with a better opportunity for survival. The variables examined were
      age, education, symptom status at first presentation: symptomatic and
      asymptomatic, date of first symptom presentation, date of first consultation with
      a health provider, consulted provider, tumor size and nodal status, according to
      the pTNM system. Time intervals were categorized into: < 1 month, 1-3 months and
      > 3 months for patient and medical delay; 1-3 months, 3-6 months, > 6 months for
      overall delay. Patient delay was associated with education: a higher risk was
      found for women with < or = 5 years school attendance (OR = 3.3, 95%, CI 2.0
      5.6). Medical delay was seen to be associated with the professional figure:
      significant differences were found between senologists (oncologist exclusively
      dedicated to breast cancer) and other specialists (OR 3.5, 95%, CI 1.5-8.4). Age
      and symptomatic presentation were found to be high risk factors. Concerning tumor
      size in overall delay in cases > 2 cm had OR values were of 2.4 (95%, CI 1.5
      3.7). In conclusion our study suggests that diagnostic delay is associated with
      medically underserved status and can be reduced by educating younger and less
      educated women, as suggested in other studies and by providing training programs
      for members in the medical profession.

PMID- 11510693
TI  - Differential expression of the early lung cancer detection marker, heterogeneous
      nuclear ribonucleoprotein-A2/B1 (hnRNP-A2/B1) in normal breast and neoplastic
      breast cancer.
AB  - Heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP-A2/B1) is highly expressed
      during critical stages of lung development and carcinogenesis. To determine if
      the expression of hnRNP-A2/B1 is an informative biomarker in breast
      carcinogenesis, we analyzed hnRNP-A2/B1 overexpression by immunohistochemistry in
      archived specimens. Expression was detected in 48/85 (56.5%) primary invasive
      breast cancers and 7/72 (9.7%) specimens of normal breast tissue. Northern
      analysis of breast cancer cells also demonstrated higher level of hnRNP-A2/B1
      expression compared to normal or transformed breast cells. Expression of hnRNP
      A2/B1 in breast cancer cells was decreased by exposure to retinoids coordinately
      with decreased cell growth. These results warrant further evaluation of hnRNP
      A2/B1 as a marker of breast carcinogenesis.

PMID- 11510694
TI  - Breast cancer survival and in vitro tumor response in the extreme drug resistance
      assay.
AB  - PURPOSE: To determine whether in vitro extreme drug resistance (EDR) assay
      results for patients with breast carcinoma were associated with clinical outcome
      after chemotherapy. PATIENTS AND METHODS: EDR assays were performed on tumor
      tissue obtained from 103 newly diagnosed breast cancer cases. EDR scores of 2 for
      low, 1 for intermediate, or 0 for extreme drug resistance were determined for
      each agent tested. In vitro EDR scores for 4-hydroxycyclophosphamide (4HC) and
      doxorubicin were summed for patients treated with AC, or for 4HC and 5-FU for
      patients treated with CMF. Treatment selection was blinded to assay results.
      RESULTS: Median time to progression was significantly shorter for patients with
      extreme or intermediate in vitro resistance (n = 55, 48 months), compared to
      patients with low in vitro resistance, (n = 41, 100 months, p = 0.022). Patients
      demonstrating extreme to intermediate drug resistance also showed poorer survival
      than the low resistance group (49.5 months vs. not reached, median follow-up 48
      months, p =0.011). Summed EDR scores, stage, and number of lymph nodes were
      significantly associated with survival in univariate and multivariate analysis.
      Compared to EDR scores of 4, summed EDR scores of 0-1 and summed EDR scores of 2
      3 were associated with a relative risk of death of 3.09 (95%, CI 1.05-9.06, Cox
      proportional hazards model, p = 0.040) and 2.35 (95%, CI 1.07-5.15, Cox
      proportional hazards model, p = 0.033), respectively. CONCLUSION: Extreme drug
      resistance testing identified patients with individual patterns of drug
      resistance prior to therapy. In this cohort of breast cancer patients treated
      with chemotherapy, summed EDR scores were significantly associated with time to
      tumor progression and overall survival. EDR results may offer a method for
      optimizing treatment selection.

PMID- 11510695
TI  - Oral gossypol in the treatment of patients with refractory metastatic breast
      cancer: a phase I/II clinical trial.
AB  - Gossypol has demonstrated in vitro effects on cell cycle regulation and anti
      tumor activity against mammary carcinoma cell lines. This Phase I/II study
      assesses both the effect of gossypol on cell cycle regulatory proteins in vivo
      and the clinical effect. Twenty women with refractory metastatic breast cancer
      received oral gossypol at daily doses between 30 and 50 mg per day. Gossypol
      plasma levels were measured (n = 8) and the modulation of the retinoblastoma (Rb)
      gene protein and Cyclin D1 was assessed by serial biopsies (n = 4). Grade I-II
      toxicities with gossypol treatment included nausea in 30% of patients, fatigue
      15%, emesis 15%, altered taste sensation 15% and diarrhea in 10% of patients. Two
      of the three patients receiving 50 mg/day experienced dose limiting dermatologic
      toxicity (grade III). One patient had a minor response and two patients had
      stable disease with > 50% decline in serial assessments of the serum tumor
      markers. Immunohistochemical analysis of cyclin D1 and Rb expression in serial
      biopsies of four patients revealed both a concurrent decrease in cyclin D1
      expression and an increase in nuclear Rb expression in three patients. The
      maximal tolerated dose (MTD) of gossypol was 40 mg/day. Gossypol appears to
      affect the expression of Rb protein and cyclin D1 in breast cancer metastases at
      doses achievable, yet had negligible antitumor activity against anthracycline and
      taxane refractory metastatic breast cancer. The cell cycle regulatory effects of
      gossypol suggest a potential role for gossypol as a modulating agent in
      conjunction with other cell cycle specific compounds.

PMID- 11510696
TI  - CK-19 expression by RT-PCR in the peripheral blood of breast cancer patients
      correlates with response to chemotherapy.
AB  - BACKGROUND: The recent introduction of sensitive RT-PCR-based techniques for the
      detection of epithelial antigen expression, such as CK-19, in the peripheral
      blood and bone marrow of breast cancer patients may provide an opportunity to
      evaluate tumor response at the molecular level, even in the absence of measurable
      disease while patients are still receiving chemotherapy. METHODS: We studied
      serially collected blood samples of 53 patients with breast cancer before,
      during, and after adjuvant, neoadjuvant, and palliative chemotherapy to evaluate
      its effects on the expression of CK-19 measured by RT-PCR. RESULTS: The
      percentage of CK-19 RT-PCR positivity decreased consistently from 43% (23/53)
      before chemotherapy to 14.3% (7/49), and to 18.9% (7/37) after 3 and 6 cycles,
      respectively (chi-square for linear trend = 7.948; p = 0.0048). Furthermore,
      there was a significant correlation between a negative CK-19 at three months and
      the response to chemotherapy (p = 0.024). CONCLUSION: We conclude that RT-PCR
      negativity for CK-19 expression at 3 months after the beginning of chemotherapy
      correlates with tumor response and, as treatment progresses, there is a
      significant trend for the occurrence of more negative RT-PCR results. Further
      studies are needed to confirm if this technique can be useful to assess response
      to chemotherapy in patients without measurable disease and if negativation of CK
      19 expression while on chemotherapy is of prognostic significance.

PMID- 11510697
TI  - Association of NK cell dysfunction with changes in LDH characteristics of
      peripheral blood lymphocytes (PBL) in breast cancer patients.
AB  - The cytotoxic activity of NK (natural killer) cells is very important in
      immunological surveillance against the appearance and especially the spread of
      malignant disease. The aim of this study was to investigate the function of this
      subpopulation of cells in breast cancer patients in different clinical stages of
      disease prior to therapy. NK cell activity was determined in breast cancer
      patients and healthy controls by three different methods: standard 51-chromium
      release assay and by the original colorimetric uncorrected and corrected lactate
      dehydrogenase (LDH) release assay. A discrepancy was shown between the assays, as
      the uncorrected LDH assay showed, not only, much higher values, but no stage
      dependent depression in NK cell activity compared to the chromium-release assay.
      Further analyses of separately cultured peripheral blood lymphocytes (PBL)
      revealed that this difference arose from an increasing, clinical stage-dependent,
      spontaneous LDH release from PBL of breast cancer patients. Furthermore, a stage
      dependent increase in intracellular LDH activity of PBL was found, although
      without difference in LDH-H and LDH-M isotype ratio, compared to controls.
      Increased spontaneous LDH release and intracellular LDH activity was more evident
      in young patients, under 40 years. Correction of the original LDH-release assay
      for the spontaneous LDH release activity from PBL present in the assay, gave
      values of NK cell activity comparable to those determined by the chromium assay
      and indicated that breast cancer patients have a significant depression in NK
      cell activity which correlates with the stage-dependent increase in spontaneous
      LDH release. Moreover, as both assays measure the secretory, perforin-mediated,
      NK cell cytotoxic pathway against tumor cells, it can be concluded that the
      appearance of spontaneous LDH release is an indicator of cell membrane damage
      which not only allows the loss of LDH, but also of the components of the
      secretory killing pathway, resulting in NK cell dysfunction with the progression
      of disease. The novel findings obtained in this work reveal the association of
      PBL membrane damage with clinical stage of breast cancer that can, aside from
      reflecting NK cell depression, underlie the defect in other PBL subsets and
      subsequently facilitate progression of the malignant process.

PMID- 11510698
TI  - Metallothionein 1F mRNA expression correlates with histological grade in breast
      carcinoma.
AB  - Immunohistochemical expression of metallothioneins (MTs), a group of
      intracellular metal-binding proteins, is well documented in breast cancer.
      However, there is a paucity of information on the expression of the different MT
      isoforms in breast cancer tissues. The dichotomous association of MT
      overexpression with tumour types and progression led us to examine the role of
      the MT-1F mRNA isoform in breast cancer. We evaluated MT expression in 48 primary
      invasive ductal breast cancer tissues by immunohistochemistry, and the
      corresponding MT-1F mRNA expression via a semi-quantitative reverse transcription
      polymerase chain reaction (RT-PCR) assay. The specificity of the RT-PCR products
      was confirmed by direct cycle sequencing and restriction enzyme digestion.
      Immunohistochemical analysis of MT revealed a significantly higher MT expression
      in histological grade 3 tumours as compared to grade 1 and 2 tumours (p = 0.021).
      Similarly, MT-1F mRNA expression was found to be significantly higher in grade 3
      tumours (p < 0.001). The results suggest that the MT-1F isoform influences
      histological differentiation in invasive ductal breast cancer. The converse is
      also true in that the histological grade may determine the level of MT-1F
      expression in breast cancer.

PMID- 11510699
TI  - Angiogenesis and reproduction.

PMID- 11510700
TI  - Is the intrauterine device appropriate contraception for HIV-1-infected women?
AB  - OBJECTIVE: To assess whether the risk of complications is higher in HIV-1
      infected women compared with non-infected women in the two years following
      insertion of the intrauterine contraceptive device. DESIGN: Prospective cohort
      study. POPULATION: Six hundred and forty-nine women (156 HIV-1-infected, 493 non
      infected) in Nairobi, Kenya who requested an intrauterine contraceptive device
      and met local eligibility criteria. METHODS: We gathered information on
      complications related to the use of the intrauterine contraceptive device,
      including pelvic inflammatory disease, removals due to infection, pain or
      bleeding, expulsions, and pregnancies at one, four, and 24 months after insertion
      by study physicians masked to participants' HIV-1 status. Cox regression was used
      to estimate hazard ratios. RESULTS: Complications were identified in 94 of 636
      women returning for follow up (14.7% of HIV-1-infected, 14.8% of non-infected).
      The incidence of pelvic inflammatory disease was rare in both infected (2.0%) and
      non-infected (0.4%) groups. Multivariate analyses suggested no association
      between HIV-1 infection and increased risk of overall complications (hazard ratio
      = 1.0; 95% CI 0.6-1.6). Infection-related complications (e.g. any pelvic
      tenderness, removal for infection or pain) were also similar between groups
      (10.7% of HIV-1-infected, 8.8% of non-infected; P = 0.50), although there was a
      non-significant increase in infection-related complications among HIV-1-infected
      women with use of the intrauterine contraceptive device longer than five months
      (hazard ratio = 1.8; 95% CI 0.8-4.4). Neither overall nor infection-related
      complications differed by CD4 (immune) status. CONCLUSIONS: HIV-1-infected women
      often have a critical need for safe and effective contraception. The intrauterine
      contraceptive device may be an appropriate contraceptive method for HIV-1
      infected women with ongoing access to medical services.

PMID- 11510701
TI  - Magnetic resonance imaging in the assessment of complex Mullerian anomalies.
AB  - OBJECTIVE: To evaluate the accuracy of magnetic resonance imaging in assessment
      of adolescent patients with complex Mullerian anomalies and its contribution
      towards operative management. DESIGN: A retrospective review of magnetic
      resonance imaging and operative findings. SETTING: A London teaching hospital
      that is a tertiary referral centre for complex reproductive tract disorders.
      SAMPLE: All adolescents referred for assessment of complex Mullerian anomalies,
      from 1996 to 1999, and undergoing both magnetic resonance imaging and surgical
      assessment. METHOD: In the nine suitable patients magnetic resonance imaging and
      surgical findings were compared and the role of magnetic resonance imaging in
      determining the route and type of surgery was evaluated. MAIN OUTCOME MEASURES:
      Magnetic resonance imaging data on reproductive tract anatomy and surgical
      findings detailing reproductive tract anatomy. RESULTS: There was good
      correlation of magnetic resonance imaging and operative findings in all cases.
      The best correlation was with uterine structure. In four cases the magnetic
      resonance imaging findings were essential for the appropriate choice of the
      surgical approach and type of procedure. CONCLUSIONS: Magnetic resonance imaging
      is a valuable tool in the management of this particular complex group of
      patients.

PMID- 11510702
TI  - Accuracy of frozen section for the operative management of endometrial cancer.
AB  - OBJECTIVE: To assess the accuracy of intra-operative frozen section reports at
      identifying the features of high risk uterine disease compared with final
      histopathology. DESIGN: Retrospective study. METHODS: The records of 460 patients
      with uterine cancer registered with the Queensland Centre for Gynaecological
      Cancer between January 1, 1996 and December 31, 1998 were reviewed. Intra
      operative frozen section was undertaken in 260 patients with endometrial
      adenocarcinoma. Frozen section pathology was compared with the final
      histopathology reports. Inter-observer reliability was assessed using percentage
      agreement and kappa statistics. Clinical notes were also reviewed to determine if
      errors resulted in sub-optimal patient care. RESULTS: Respectively, tumour grade
      and depth of myometrial invasion were accurately reported in 88.6% of cases
      (expected 61.5%, Kappa 0.70) and 94.7% (expected 53.8%, Kappa 0.89). Errors were
      predominantly attributable to difficulties with respect to the interpretation of
      tumour grade. The error resulted in the patient receiving sub-optimal surgical
      management in only 11 cases (5.3%) CONCLUSION: Frozen section is accurate at
      identifying the features of high risk uterine disease in the setting of
      endometrial cancer and can play an important role in directing primary operative
      management.

PMID- 11510703
TI  - Increased levels of interleukin-10 and transforming growth factor-beta in the
      plasma and ascitic fluid of patients with advanced ovarian cancer.
AB  - OBJECTIVES: To assess expression of the immunosuppressive cytokines IL-10 and TGF
      beta in the ascitic fluid and plasma of advanced ovarian cancer patients. DESIGN:
      A prospective study. SETTING: The Department of Obstetrics and Gynaecology at the
      University of Arkansas for Medical Sciences. POPULATION: Twenty-eight women
      diagnosed with advanced ovarian cancer and ten normal female controls. METHODS:
      Plasma and ascitic samples were collected at the time of surgery and analysed for
      the presence of IL-10 and TGF-beta using a sensitive enzyme-linked immunosorbent
      assay. RESULTS: Elevated levels of IL-10 were detected in the plasma [mean (SD) =
      12 (5) pg/mL; range 8 to 23 pg/mL] and in the peritoneal fluid [mean (SD) = 165
      (137) pg/mL; range 50 to 556 pg/mL] of ovarian cancer patients, while no
      detectable IL-10 was found in any of the normal control plasma samples tested.
      Similarly, plasma levels of TGF-beta in ovarian cancer patients were
      significantly higher [mean (SD) = 1,506 (246) pg/mL; range 1,020 to 2,070 pg/mL]
      compared with controls [mean (SD) = 937 (187) pg/mL; range 770 to 1,140 pg/mL](P
      < 0.001). Surprisingly, however, although elevated TGF-beta levels were also
      detected in the peritoneal fluid of all ovarian cancer patients [mean (SD) = 407
      (158) pg/mL; range 140 to 770 pg/mL], these levels were significantly lower than
      those seen in matched plasma samples (P < 0.001). CONCLUSIONS: Local and systemic
      secretion of immunosuppressive cytokines may play an important role in the
      impaired anti-tumour immune function commonly observed in advanced ovarian
      cancer. However, the observation that plasma levels of TGF-beta are significantly
      higher than those detected in the ascitic fluid raises the possibility that cells
      other than tumour cells are responsible for TGF-beta release in the bloodstream
      of these patients.

PMID- 11510704
TI  - Influence of peritoneal factors on port-site metastases in a xenograft ovarian
      cancer model.
AB  - OBJECTIVE: We determine the main physical effects of pneumoperitoneum on tumour
      dissemination and port-site metastases occurrence. DESIGN: A prospective
      randomised study in rats. METHODS: A human ovarian cancer cell line (IGR-OV1) was
      xenografted in nude rats. Seven days after cancer inoculation, surgery was
      performed. Rats were randomised in two main groups and underwent either: gasless
      laparoscopy (n = 20) CO2 laparoscopy with pneumoperitoneum pressure at 4 mmHg (n
      = 20), or 8 mmHg (n = 20) with in each case, increasing operative duration:
      30,60,90 or 120 minutes (five rats for each time). Animals were killed seven days
      after the intervention. MAIN OUTCOME MEASURES: Tumour dissemination and frequency
      of port-site metastases. RESULTS: Tumour dissemination was not influenced by gas
      pressures or duration of procedure. The rate of rats with at least one port-site
      metastasis (one or two) was similar in all groups: gasless: n = 10/20; 4 mmHg
      CO2: 5/20; 8 mmHg CO2: 7/20,(P = 0.26). The number of port-site metastases were
      significantly higher in the gasless group compared with the 4 mmHg CO2 group
      (15/40 (37.5%) vs 5/40 (12.5%), P = 0.01). Difference was not significant between
      the 8mmHg group and the gasless group (9/40(22.5%) vs 15/40(37.5%), P = 0.14) or
      the 4mmHg group (9/40(37.5%) vs 5/40 (12.5%), P = 0.24). Duration of procedures
      had no significant influence on port-site metastases rate (P > 0.05).
      CONCLUSIONS: Unlike previous animal studies, port-site metastases were more
      frequent with gasless laparoscopy than with CO2 pneumoperitoneum. Local
      peritoneal factors could play an important role in port-site metastases
      mechanism.

PMID- 11510705
TI  - Cellular proliferation in the female lower urinary tract with reference to
      oestrogen status.
AB  - OBJECTIVE: To assess cell proliferation throughout the tissues of the female
      lower urinary tract and to compare cell proliferation rates in women of varying
      oestrogen status. DESIGN: Prospective observational study. SETTING: A large
      teaching hospital. SAMPLE: Fifty-nine women undergoing surgery for
      urogynaecological conditions of whom 23 were premenopausal, 20 were
      postmenopausal and taking no oestrogen supplementation and 16 were postmenopausal
      and receiving some form of hormone replacement therapy. Biopsies were taken
      during surgery from the bladder dome, trigone, the proximal and distal urethra,
      vagina and vesico-vaginal fascia in the region of the bladder neck. METHODS:
      Formalin-fixed paraffin-embedded biopsies were labelled by an avidin-biotin
      technique with a monoclonal antibody raised against part of the nuclear matrix
      known as Ki-67 antigen. MAIN OUTCOME MEASURES: Ki-67 expression was assessed in
      the epithelial, subepithelial and muscle or deep fascial regions of all tissues
      and related to oestrogen status. RESULTS: Ki-67 expression was only found in high
      levels in biopsies containing squamous epithelia. Significantly higher levels of
      Ki-67 expression were observed in the tissues of oestrogen replete women in the
      premenopausal and hormone replacement groups, compared with postmenopausal women
      receiving no oestrogen supplementation. CONCLUSIONS: Squamous epithelia of the
      female lower urinary tract exhibit greater levels of cell proliferation in
      oestrogen replete as compared with oestrogen deficient women. As these same
      squamous epithelia also consistently express oestrogen receptors, the findings
      suggest a mechanism by which oestrogen exerts its effect on the lower urinary
      tract and also provide an explanation for the success of oestrogen in the
      treatment of some conditions causing lower urinary tract dysfunction in
      postmenopausal women.

PMID- 11510706
TI  - Sacrospinous ligament fixation for massive genital prolapse in women aged over 80
      years.
AB  - OBJECTIVE: To assess the feasibility of vaginal sacrospinous ligament fixation
      for women over 80 years of age with massive vaginal vault or uterovaginal
      prolapse. DESIGN: Retrospective observational study with long term follow up.
      SETTING: Department of Obstetrics and Gynaecology, Tampere University Hospital,
      Finland. SAMPLE: and Methods The study group consisted of 25 women with a mean
      (SD) [range] age of 83 (3) [80-93] years: 13 had posthysterectomy vaginal vault
      prolapse and 12 had massive uterovaginal prolapse. All underwent vaginal
      sacrospinous ligament fixation with repair of pelvic floor relaxation. Women with
      uterovaginal prolapse also underwent concomitant vaginal hysterectomy. The long
      term outcome was assessed in 19 women. The mean follow up period was 33 (31) [2
      113] months. MAIN OUTCOME MEASURES: Intra- and post-operative morbidity,
      mortality and recurrence of prolapse. RESULTS: Sixteen of the 25 women (64 %) had
      no major intra- or post-operative complications. The mean estimated blood loss
      was 400 (280) mL, and seven women received blood transfusions. Four women (16%)
      had cardiovascular complications, and one died of pulmonary embolism. All four
      had a history of vascular disease. One woman had symptomatic recurrence of vault
      prolapse treated with a vaginal pessary; two women had asymptomatic cystocele and
      one had an enterocele requiring no treatment. The outcomes were similar for women
      with or without concurrent vaginal hysterectomy. CONCLUSION: Transvaginal
      sacrospinous ligament fixation is an effective treatment for massive vaginal
      vault or uterovaginal prolapse in aged women. Increased blood loss may elevate
      the risk of cardiovascular complications especially in elderly patients with a
      history of vascular disease, thus indicating the importance of intraoperative
      bleeding control.

PMID- 11510707
TI  - Chronological aspects of ultrasonic, hormonal, and other indirect indices of
      ovulation.
AB  - OBJECTIVE: To improve prediction of ovulation in normal cycles. DESIGN:
      Collection of women's characteristics and their menstrual cycles. Monitoring and
      analysis of time relationships between several indicators of ovulation:
      transvaginal ultrasonography, cervical mucus, basal body temperature, urinary
      luteinising hormone, and ratio of urinary oestrogen to progesterone metabolites.
      SETTING: Each of eight natural family planning clinics was to study 12 women for
      at least three cycles. POPULATION: One hundred and seven normally fertile and
      cycling women aged 18 to 45. METHODS: Daily measurements of urinary luteinising
      hormone, follicle stimulating hormone, oestrone-3-glucuronide and pregnanediol
      3alpha-glucuronide. Basal body temperature recording and cervical mucus checking.
      Transvaginal ultrasound examination of the ovaries. MAIN OUTCOME MEASURES: Delays
      between the expected day of ovulation according to the luteinising hormone peak
      or to ultrasound evidence and the expected days according to the other indices of
      ovulation. RESULTS: Ultrasonography was able to show evidence of ovulation in 283
      out of 326 cycles. The average time lag between luteinising hormone peak and
      ultrasound evidence was less than one day (+0.46) but premature and late
      luteinising hormone-expected date of ovulation were observed in nearly 10% and
      23% of cycles, respectively. Basal body temperature rise was observed in 98% of
      cycles. Cervical mucus peak symptom, rapid drop in the ratio of urinary
      metabolites, and luteinising hormone initial rise were all close to
      ultrasonographic evidence in more than 72% of cycles. CONCLUSIONS: For accuracy
      and practical reasons, the cervical mucus peak symptom, the ratio of urinary
      metabolites and luteinising hormone initial rise might be better indices of
      ovulation than the luteinising hormone peak.

PMID- 11510708
TI  - Perinatal outcome in SGA births defined by customised versus population-based
      birthweight standards.
AB  - OBJECTIVE: To determine whether customised birthweight standard improves the
      definition of small for gestational age and its association with adverse
      pregnancy outcomes such as stillbirth, neonatal death, or low Apgar score.
      DESIGN: Population based cohort study. POPULATION: Births in Sweden between 1992
      95 (n = 326,377). METHODS: Risks of stillbirth, neonatal death, and Apgar score
      under four at five minutes were calculated for the lowest 10% birthweights
      according to population-based and customised standards, and were compared with
      the data from the group with birthweights over this limit. Population
      attributable risks for stillbirth using various birthweight centile cutoffs were
      calculated for the two standards. OUTCOME MEASURES: Odds ratios and 95%
      confidence intervals for stillbirth, neonatal death and Apgar score under four at
      five minutes, and population attributable risks for stillbirth at different
      birthweight centiles. RESULTS: Risks of stillbirth, neonatal death, and Apgar
      score under four at five minutes and population attributable risks of stillbirth
      were consistently higher if 'small for gestational age' was classified by a
      customised rather than by the population-based birthweight standard. Compared
      with infants who were not small for gestational age by both standards, the odds
      ratio for stillbirth was 6.1 (95% CI 5.0-7.5) for small for gestational age by
      customised standard only, whereas it was 1.2 (95 % CI 0.8-1.9) for small for
      gestational age by population standard only. CONCLUSIONS: Compared with the
      population-based birthweight standard, a customised birthweight standard
      increases identification of fetuses at risk of stillbirth, neonatal death and
      Apgar score under 4 at 5 minutes, probably due to improved identification of
      fetal growth restriction.

PMID- 11510709
TI  - A randomised double-blind placebo controlled trial of low molecular weight
      heparin as prophylaxis in preventing venous thrombolic events after caesarean
      section: a pilot study.
AB  - OBJECTIVE: To pilot a protocol for a national multicentre randomised trial in
      which a low molecular weight heparin will be compared with placebo for prevention
      of venous thrombotic events occurring within six weeks after caesarean section.
      DESIGN: Double-blind randomised controlled trial. SETTING: Tertiary care centre.
      PARTICIPANTS: Seventy-six women having had a caesarean section, 37 in the control
      group and 39 in the Dalteparin group. METHODS: Consenting patients having had an
      emergency or elective caesarean section were commenced on study medication 6-24
      hours post-operatively. The study medication, dalteparin 2,500 iu or saline, was
      given subcutaneously once daily for four or five days post-operatively depending
      on the patient's length of stay. Patients were reviewed in hospital for operative
      outcomes and contacted at two and six weeks post-operatively. RESULTS: Of the 141
      women given information about the trial, 76 (54%) consented to participate.
      Follow up to six weeks was achieved in all women who were recruited. More women
      in the placebo arm had general anaesthesia, but otherwise the two groups had
      similar characteristics at randomisation. There was only one occurrence of a deep
      vein thrombosis during the study. This patient was in the treatment arm and the
      thrombosis occurred between two and six weeks post-operatively. All other
      outcomes were similar in the two groups. CONCLUSION: Our experience of a 26%
      recruitment rate, the thrombosis rate of 1.3% (95% CI 0.03-7.1%) and the
      contactability of all participants two and six weeks post-operatively, indicates
      that this study is feasible.

PMID- 11510710
TI  - Choosing a strategy to prevent neonatal early-onset group B streptococcal sepsis:
      economic evaluation.
AB  - OBJECTIVE: To determine the most appropriate strategy to prevent neonatal
      streptococcal sepsis in a setting with a low incidence of the disease. DESIGN:
      Decision analysis and economic evaluation. SETTING: Geneva University Hospitals,
      Switzerland. POPULATION: Pregnant women at 35-37 weeks of gestation and in
      labour. METHODS: Local data and data from the literature were used in a decision
      analysis to compare the current policy of antibiotic administration at Geneva
      University Hospitals with the recommended preventive strategies. MAIN OUTCOME
      MEASURES: Number of episodes of sepsis averted; cost and number needed to treat
      to prevent one episode of sepsis; and proportion of women receiving antibiotics
      during labour. RESULTS: Compared with the current policy, the risk factors
      strategy would prevent 69 streptococcal sepsis per million deliveries and the
      screening strategy would prevent 102 cases of sepsis per million deliveries. Cost
      per averted sepsis case would be 60 pounds, 700 and 473 pounds, 600,
      respectively. The number needed to treat to prevent one sepsis would be 1,087
      with a risk factors strategy and 1,029 with a screening strategy. Preventive
      strategies would increase the proportion of women receiving antibiotics during
      labour from 6% with the current policy, to 13.5% and 16.5% respectively.
      CONCLUSIONS: Preventive strategies are more effective than the current policy,
      but imply increased hospital costs and a notable increase in the proportion of
      women receiving antibiotics during labour, which may be unjustified in a low
      incidence setting.

PMID- 11510711
TI  - Computerised analysis of the fetal heart rate and relation to acidaemia at
      delivery.
AB  - OBJECTIVE: To identify the individual features of the computerised analysis of
      the cardiotocograph that relate to arterial pH and base deficit at delivery.
      DESIGN: Retrospective observational study. SETTING: Teaching hospital labour
      wards. PARTICIPANTS: 679 women requiring continuous intrapartum fetal monitoring.
      METHODS: Fetal heart and uterine contraction data were obtained using the
      Nottingham Fetal ECG monitor. Fetal heart rate patterns for the last half-hour
      preceding delivery were analysed using a computer algorithm developed for
      intrapartum application. The significance of the areas under receiver operator
      characteristic curves were calculated. MAIN OUTCOME MEASURES: Umbilical arterial
      pH and base deficit at delivery. RESULTS: Three parameters, fetal bradycardia,
      total deceleration area and the deceleration area after a contraction had
      receiver operator characteristic curves that significantly predict a low
      umbilical arterial pH and base deficit at delivery (areas under receiver-operator
      characteristic curves = 0.53, SD 0.01 P = 0.03; 0.60, SD 0.03 P = 0.002; 0.62 SD
      0.04 P < 0.001, respectively). Tachycardia, accelerations and variability did
      not. CONCLUSIONS: The individual components of the computerised analysis of the
      fetal heart rate that predict acidaemia at delivery are identified.

PMID- 11510712
TI  - Computerised analysis of fetal heart rate recordings in maternal type I diabetes
      mellitus.
AB  - OBJECTIVE: 1. To study computerised cardiotocograph parameters from women with
      type I diabetes; 2. to examine the significance of observed differences from the
      expected normal values. DESIGN: Prospective observational study in the third
      trimester of pregnancy. SETTING: The medical antenatal clinic of a tertiary
      referral centre. POPULATION: Twenty-six women with type I diabetes mellitus with
      a singleton pregnancy. METHODS: Computerised cardiotocograph recordings were made
      weekly from 28 to 39 weeks. Derived parameters were compared with the published
      figures for uncomplicated singleton pregnancies. Details of maternal blood sugar,
      labour and delivery and neonatal outcome were recorded. Data were compared
      between groups according to the computerised analysis of the antenatal CTGs.
      RESULTS: One-hundred and thirty-one recordings were made with a median of five
      per patient (range 1-12). 1 1.3% showed absent episodes of high variation
      compared with the expected value of 0.8%, a difference of 9.5% (95% CI 4.5-15.3).
      Differences in short term variation, basal heart rate, frequency of fetal
      movements and heart rate accelerations were also found which changed with
      gestation. Overall these changes represented a more immature form of fetal heart
      rate than that which would be expected. No relationship between the changes and
      adverse fetal outcome could be identified. CONCLUSIONS: Significant differences
      exist in cardiotocographs in maternal type I diabetes compared with normal
      fetuses. The changes may represent a delay in fetal maturation. The analysis mode
      of the computer will register these as abnormal features, but there is no
      evidence that they are pathological. We would recommend that computerised
      analysis is not used to assess pregnancies complicated by maternal type I
      diabetes mellitus.

PMID- 11510713
TI  - Computerised antenatal fetal heart rate recordings between 24 and 28 weeks of
      gestation.
AB  - OBJECTIVE: To assess computerised fetal heart rate recordings between 24 and 28
      weeks of gestation for gestation related differences. DESIGN: Prospective, cross
      sectional observational study. SETTING: Liverpool Women's Hospital. POPULATION:
      112 women: 28 at 27 weeks, 30 at 26 weeks, 27 at 25 weeks and 27 at 24 weeks of
      gestation, respectively. METHODS: Fetal heart recordings of 60 minutes duration
      were performed once in each pregnancy using the System 8000 fetal heart rate
      programme (System 8000, Oxford Sonicaid Ltd, Chichester, UK). For each
      gestational age, records were analysed for short term variation, basal heart
      rate, accelerations and time spent in high episodes. RESULTS: The mean short term
      variation increased with gestation (P = 0.05). No record had a short term
      variation <4 msecs. There was no relationship between heart rate and increasing
      gestation. The mean number of accelerations per record increased with increasing
      gestation (P < 0.01). 20% of recordings showed no accelerations > 15 bpm. The
      mean duration spent in episodes of high variation increased with gestation (P =
      0.05). 13% of recordings showed no time spent in high episodes. All fetuses had
      normal outcomes at delivery. CONCLUSIONS: Absence of episodes of high variation
      or absence of accelerations is not an abnormal finding at lower gestations. The
      standard threshold of 4 msecs for short term variation appears to remain valid at
      lower gestations. These differences should be considered when using computerised
      CTG analysis at early gestations.

PMID- 11510714
TI  - Fetal lung volume measurement by magnetic resonance imaging in congenital
      diaphragmatic hernia.
AB  - OBJECTIVE: To study the potential for prenatal magnetic resonance imaging to
      predict pulmonary hypoplasia in congenital diaphragmatic hernia. DESIGN:
      Prospective observational study. SETTING: Tertiary care centre. PARTICIPANTS:
      Thirteen cases of congenital diaphragmatic hernia (11 left, 2 right) without
      associated anomalies and 74 controls. METHODS: Measurements by magnetic resonance
      imaging of fetal lung volume were achieved. In the control fetuses, a regression
      analysis was performed to associate fetal lung volume with gestational age. This
      yielded a formula allowing calculation of the expected fetal lung volume as a
      function of gestational age. In the cases with congenital diaphragmatic hernia,
      the observed/expected fetal lung volume ratio was compared with perinatal
      outcome. MAIN OUTCOME MEASURES: Neonatal mortality and pulmonary hypoplasia,
      which was defined as lung/body weight ratios less than 0.012. RESULTS: The
      expected fetal lung volume was derived from the following formula: Fetal lung
      volume (mL) = exp (1.24722 + 0.08939 x gestational age in weeks). The
      observed/expected fetal lung volume ratio was significantly lower in congenital
      diaphragmatic hernia (median: 0.31, range: 0.06-0.63), than in controls (median:
      0.99, range: 0.42-1.94). This ratio was significantly less in the infants with
      congenital diaphragmatic hernia who died (median: 0.26, range: 0.06-0.63)
      compared with those who survived (median: 0.46, range: 0.35-0.56). The observed:
      expected fetal lung volume ratio was significantly correlated with the post
      mortem lung: body weight ratio. CONCLUSION: In isolated congenital diaphragmatic
      hernia, fetal lung volume measurement by magnetic resonance imaging is a
      potential predictor of pulmonary hypoplasia and postnatal outcome. Further
      studies are required to establish the clinical value of magnetic resonance
      imaging for the prenatal assessment of fetal lungs.

PMID- 11510715
TI  - Activin betaA-subunit and activin receptors in human myometrium at term and
      during labour.
AB  - OBJECTIVE: To measure activin A content and to localise and semi-quantitate
      activin receptors in human myometrium at term and during labour. DESIGN:
      Myometrium was collected from non-pregnant women (n = 6), pregnant women at term
      not in labour (n = 6) and at term in labour (n = 6). SETTING: Monash Medical
      Centre, Melbourne, Australia. MAIN OUTCOME MEASURES: Tissue lysates of myometrium
      were analysed for activin A content using an enzyme-linked immunosorbent assay
      and activin receptor proteins IA, IIA and IIB using Western hybridisation.
      Activin betaA-subunit and activin receptors were localised in myometrium by
      immunohistochemistry. RESULTS: Activin A was detected by ELISA in non-pregnant,
      pregnant and labouring myometrium. Levels were significantly higher in labouring
      myometrium. The three activin receptors IA, IIA and IIB were detected in all
      myometrial samples by Western hybridisation. Receptor IA was expressed in
      significantly higher levels in pregnant myometrium. Receptor IIA was very weakly
      expressed throughout. The expression of receptor IIB was similar in all three
      groups. Activin betaA-subunit and all three receptors were localised to the
      endothelial cells of myometrial blood vessels. Neither activin betaA-subunit nor
      any of the three activin receptors were immunolocalised to myometrial smooth
      muscle cells in the three groups. This result was confirmed by Western blotting
      for expression of activin receptors in isolated myometrial smooth muscle and
      microvascular endothelial cells. CONCLUSION: The myometrium is not a target for
      activin A during late pregnancy or labour. However, activin A may have a role in
      the regulation of microvascular endothelial cell function in the myometrium.

PMID- 11510716
TI  - Combination of cervical interleukin-6 and -8, phosphorylated insulin-like growth
      factor-binding protein-1 and transvaginal cervical ultrasonography in assessment
      of the risk of preterm birth.
AB  - OBJECTIVE: To determine the value of combinations of cervical interleukin-6 (IL
      6), cervical interleukin-8 (IL-8), the phosphorylated isoform of insulin-like
      growth-factor binding protein-1 (IGFBP-1), and cervical ultrasonography in the
      prediction of preterm birth. DESIGN: Prospective follow up. SETTING: Oulu
      University Hospital maternity clinic from February 1997 to July 1998. POPULATION:
      Women with singleton pregnancies (n = 77), referred from outpatient clinics at 22
      32 weeks of gestation with symptoms (uterine contractions) or signs (cervical
      change) of threatened preterm birth. Symptomless women (n = 78) matched for
      gestational age, parity and maternal age at recruitment were studied as a
      reference group. METHODS: A urine sample for bacterial culture was collected, and
      cervical swab samples for assays of interleukin-6 and -8 and phoshorylated IGFBP
      1 were taken before digital cervical examination. A Pap smear for analysis of
      bacterial vaginosis and samples for analysis of chlamydia and streptococci were
      also obtained. Cervical measurements were made by transvaginal ultrasonography.
      The same sampling and cervical measurement were repeated twice at two-week
      intervals. The cutoff values of the markers were determined by receiver-operating
      characteristic curve analysis. MAIN OUTCOME MEASURE: Preterm birth (<37 weeks).
      RESULTS: The preterm birth (<37 weeks) rate for women in the study group was 16%
      (12/77). The cervical interleukin-6 cutoff value (61 ng/L) at first visit had a
      sensitivity of 73% and a specificity of 61% in predicting preterm birth, with a
      positive likelihood ratio (LR+ ) of 1.9 (95% CI 1.2-3.0). An ultrasonographically
      measured cervical index value of > 0.36 at recruitment predicted preterm birth in
      25% (5/20) of the study group compared with 9% (5/54); LR+ 2.2 (95% CI 1.03-4.7).
      Cervical phosphorylated IGFBP-1 > 6.4 microg/L [LR+ 1.8 (95% CI 0.7-2.9)],
      interleukin-8 > 3739 ng/L [LR+ 1.4 (95% CI 0.9-2.4)], and ultrasonograpic
      cervical length < 29.3 mm [LR+ 2.7 (95% CI 0.8-9.7)] increased the risk of
      preterm birth. According to the logistic regression model, a combination of IL-6,
      and IL-8 and cervical index increased the specificity to 97%, but the sensitivity
      fell to 30% in detecting preterm birth. There was a significantly increased
      incidence of puerperal infections if phosphorylated IGFBP-1 concentrations were
      elevated (> 21.0 microg/L), 36% (4/11) compared with 4.6% (3/65), LR+ 6.7 (95% CI
      2.7-17), the sensitivity being 67% (4/6) and the specificity 90% (63/70).
      Elevated phosphorylated IGFBP-1 concentrations (> 21.6 microg/L) were also
      associated with an increased risk of neonatal infections; LR+ 8.0 (95% CI 3.5
      18). CONCLUSIONS: An increase in cervical IL-6 concentration and the
      ultrasonographically measured cervical index appear to be associated with preterm
      birth. A combination of these markers with measurement of cervical IL-8 appears
      to be the best predictor of preterm birth. Neither the sensitivity nor
      specificity of the tests used in this study are good enough to predict preterm
      birth for clinical decision making. Cervical phosphorylated IGFBP-1 seems to be a
      marker of puerperal and neonatal infectious morbidity in cases of threatened
      preterm delivery, suggesting early tissue degradation at the choriodecidual
      interface.

PMID- 11510718
TI  - Atosiban for the primary prevention of preterm labour.

PMID- 11510717
TI  - Radical trachelectomy in early stage carcinoma of the cervix: outcome as judged
      by recurrence and fertility rates.
AB  - The recurrence and fertility rates in 30 women undergoing radical trachelectomy
      for early stage invasive cervical cancer at St Bartholomew's and Royal Marsden
      Hospital were reviewed. There were no recurrences, and the mean follow up was 23
      months (range 1-64 months). Of 13 women trying to have a baby, eight had
      conceived with a total of 14 pregnancies and nine live births. Two were still
      trying and three were experiencing sub-fertility. There were seven premature
      deliveries and one late miscarriage. Six of the preterm births and the late
      miscarriage were associated with prelabour spontaneous rupture of membranes. This
      conservative yet locally radical procedure for a highly selected group of women
      who wished to preserve their fertility appears to offer a safe alternative to
      radical hysterectomy in early invasive cervical cancer.

PMID- 11510719
TI  - Conservative vaginal surgery for cervical pregnancy.

PMID- 11510720
TI  - A case of vaginal argyrosis: all that glistens isn't gold.

PMID- 11510721
TI  - Successful delivery of monoamniotic triplets.

PMID- 11510724
TI  - Changing trends in angioedema.
AB  - Angioedema can be a life-threatening event presenting to otolaryngologists,
      emergency medicine physicians, and other physicians. Recent reports suggest an
      increasing role of angiotensin-converting enzyme inhibitors (ACEIs) in the
      causation of angioedema. Sixty-four cases occurring between 1994 and 1998 were
      identified and examined retrospectively. Fifty-eight percent of patients
      presenting with angioedema were using ACEIs. Ninety-four percent of patients
      overall, and 92% of patients with ACEI-associated angioedema, were African
      American. Tongue, lip, facial, and supraglottic edema were most common. Treatment
      included intubation in 13% and intensive care unit monitoring in 20%. Nearly all
      patients were treated with corticosteroids and antihistamines. There were no
      deaths. Angioedema associated with ACEI use appears to be much more common than
      previously reported. African-American patients may be at higher risk for
      angioedema with ACEI use. Successful management was achieved with observation,
      expectant airway management, corticosteroids, and discontinuation of ACEIs.
      Patients without airway obstruction or pharyngeal or laryngeal edema who improved
      with treatment and observation were successfully treated as outpatients.

PMID- 11510725
TI  - Comparison of microflap healing outcomes with traditional and microsuturing
      techniques: initial results in a canine model.
AB  - A prospective, blinded study was designed to determine whether placement of a
      microsuture in epithelial defects created on canine vocal folds results in
      histologically demonstrable improved heating. Epithetial defects similar to those
      created during microflap removal were made by means of traditional microsurgical
      techniques on both vocal folds of 4 adult dogs. One vocal fold defect on each dog
      was then closed with a single microsuture placed through the laryngoscope. The
      larynges were harvested approximately 6 weeks later, and blinded histologic
      quantification of scar formation was performed. Microsutures resulted in less
      scarring in all but 1 of the larynges studied. Unsutured vocal folds exhibited a
      75% larger average scar cross-sectional area. Although the sample size was
      insufficient to establish statistical significance, the observed difference in
      scar formation between microsutured and unsutured vocal folds suggests that
      primary closure with a microsuture in the canine model results in less scarring
      than when healing occurs by secondary intention.

PMID- 11510726
TI  - Avoiding intubation in the injured subglottis: the role of heliox therapy.
AB  - Intubation in the child presenting with severe viral tracheobronchitis or prior
      subglottic injury can be detrimental to the child and the subglottis. Intubation
      may lead to further mucosal ischemia, scar, subglottic stenosis, or failed
      extubation requiring a tracheotomy. Heliox is a combination of helium and oxygen
      that produces less-dense gas exchange. Its use leads to a decrease in turbulent
      airflow, which may obviate the need for intubation. Here we report our experience
      using heliox as initial therapy in 14 consecutive children presenting with severe
      airway distress and the need for intubation. (Five had viral tracheobronchitis, 5
      had inflammatory exacerbation of subglottic stenosis, and 4 had acute iatrogenic
      subglottic injury.) In 10 of the 14 children, intubation, which can lead to
      mucosal injury and scarring, was avoided by the use of heliox therapy. Of the 4
      children in whom heliox therapy failed, 3 had a prior history of subglottic
      stenosis. Heliox is a relatively safe and reliable alternative to intubation of
      children with severe subglottic edema or injury. Heliox should be considered
      before intubation for selected children with subglottic inflammation and severe
      airway distress.

PMID- 11510727
TI  - Tracheal reconstruction with a synthetic material in a porcine model.
AB  - The technique of tracheal reconstruction with costal cartilage or a pericardial
      patch has resulted in successful management of many patients with tracheal
      stenosis. Yet, it is often difficult, if not impossible, to harvest enough
      cartilage in a neonate. Pericardial patches are flimsy and can collapse. This
      pilot study evaluated the use of absorbable plates made of an alloplastic
      material, Lactosorb, as a substitute for cartilage on a growing porcine trachea.
      The rectangular plates were fashioned into an inverted U and placed into the
      airway through an anterior tracheal split. This placement resulted in granulation
      formation and failure. The plates were then fashioned into an I configuration and
      placed inside and outside the tracheal lumen. This attempt also resulted in
      failure, secondary to respiratory distress. Finally, the plates were fashioned
      into an inverted U and placed outside the trachea. In 67% of the subjects, the
      distraction was maintained and growth continued for the duration of the study.
      The stent was completely absorbed, with minimal scar or granulation tissue, in 4
      months. In 1 subject, the stent migrated, and 1 subject died of a mucous plug.
      This study suggests that Lactosorb has no role in intraluminal stenting, but that
      it may be a viable alternative to a pericardial patch or cartilage in tracheal
      reconstruction when it is placed outside the airway lumen in a young animal.

PMID- 11510728
TI  - Pediatric bilateral vocal fold immobility: the role of carbon dioxide laser
      posterior transverse partial cordectomy.
AB  - Vocal fold paralysis in children has been estimated to be the second most common
      congenital abnormality of the pediatric airway. Most commonly, children present
      with the vocal folds in the midline or adducted position. Pediatric patients
      usually have a good voice or cry and a poor airway. In these cases, the surgical
      goal will be improving the airway, usually by lateralizing a vocal fold, while
      maintaining a normal voice and intact swallowing. The focus of this article is a
      modification of a technique for use in adults that was introduced by Dennis and
      Kashima in 1989. The procedure is intended to separate the vocal ligament and
      vocalis muscle from the arytenoid cartilage with removal of significant tissue
      mass with the CO2 laser. The demographics and results of 5 pediatric patients who
      underwent this procedure are discussed. The preoperative goals of airway
      enlargement, voice preservation, and normal deglutition were achieved in all 5
      patients.

PMID- 11510730
TI  - Thyroglossal duct carcinoma: a large case series.
AB  - Thyroglossal duct cysts (TDCs) are common congenital abnormalities of thyroid
      development. Carcinoma occurs rarely in patients with TDCs. In a large case
      series drawn from medical records at a health maintenance organization from 1971
      through 1995, 14 cases of carcinoma in a TDC were found. This represents the
      largest known reported case series to date. Demographics, diagnosis, and
      treatment methods are reviewed. We recommend the Sistrunk operation and
      evaluation of the thyroid gland and neck for potential abnormality that would
      necessitate thyroidectomy and lymph node dissection. Long-term follow-up
      incorporating clinical examination is mandatory.

PMID- 11510729
TI  - Laryngospasm and diaphragmatic arrest in immature dogs after laryngeal acid
      exposure: a possible model for sudden infant death syndrome.
AB  - Laryngopharyngeal reflux has been proposed as a possible cause of sudden infant
      death syndrome (SIDS). We investigated the efferent laryngeal and diaphragmatic
      responses to acid exposure on the laryngeal mucosa using a neonatal canine model.
      Electromyographic (EMG) recordings from the thyroarytenoid muscle and the
      diaphragm were measured with hooked-wire electrodes. Reproducible laryngospasm
      responses occurred in all animals after laryngeal exposure to hydrochloric acid
      at pH 2.0 or less. Laryngospasm occurred in combination with tachypnea and
      increased diaphragmatic activity in most of the animals. Laryngospasm was
      associated with prolonged apnea and total cessation of diaphragmatic EMG activity
      in 1 animal, and in another, initial tachypnea was followed by erratic
      diaphragmatic activity and brief apnea. Laryngeal acid exposure (below pH 2.0)
      causes laryngospasm and may result in paradoxical apneic events in neonatal dogs.
      Acid-induced, laryngospasm-associated apnea may represent a potential cause of
      SIDS, and the immature dog appears to be an excellent model for further
      investigations.

PMID- 11510731
TI  - Transcanal atticoaditotomy and transcortical mastoidectomy for cholesteatoma: the
      Farrior-Olaizola technique revisited.
AB  - Conservative mastoid surgery in the management of middle ear cholesteatoma has
      been a subject of controversy for decades. Proponents of the combined-approach
      tympanoplasty for cholesteatoma do not entirely support the conservative approach
      in children, especially in the hands of an inexperienced surgeon. We describe
      here our experience with a modified technique of conservative mastoid surgery
      involving an atticoaditotomy and a separate simple mastoidectomy with lateral
      attic wall reconstruction (modified Farrior technique) that can be relatively
      safely used in the majority of cases of chronic squamous otitis media, even in
      children. This was a prospective analysis of the therapeutic effects and benefits
      of the technique used in 103 cases of cholesteatoma at Staffordshire General
      Hospital from 1991 to 1997. The follow-up was between 3 and 9 years. The study
      group consisted of 55 male patients and 48 female patients, including 28 children
      less than 16 years of age. The age ranges were 9 to 61 years in male patients and
      10 to 48 years in female patients. After an audiological assessment, all patients
      underwent the described mastoid procedure, and some of them required revision
      surgery, mostly for a second look or for ossiculoplasty. The chief outcome
      measures used were complete eradication of disease, incidence of disease
      recurrence, and restoration of hearing. The steps of the procedure, its pros and
      cons, and the results of the series are presented. Also discussed is an overview
      of the literature pertaining to intact-canal wall mastoid surgery. Of the 103
      patients, only 3 had a recurrence of disease, and 9 patients showed no hearing
      improvement. We conclude that this modified technique has several advantages over
      the previously described mastoidectomy procedures. It is a relatively simple and
      effective technique that can be performed even in children.

PMID- 11510732
TI  - Failure of grommet insertion in post-irradiation otitis media with effusion.
AB  - Nasopharyngeal carcinoma (NPC) survivors with post-irradiation otitis media with
      effusion (OME; 100 ears) were divided into 2 groups. One group underwent grommet
      insertion, and the other group was treated by repeated myringotomies plus
      aspiration to evaluate the outcome of the OME. Computed tomography, magnetic
      resonance imaging, audiometry, and local checks of the ear, nose, and
      nasopharyngeal fields were performed to evaluate the sinus and middle ear
      conditions over a long-term (more than 10 years) follow-up period. The results in
      these NPC survivors with OME indicated that the prevalence of middle ear
      complications in the myringotomized group (33%) was less than that in the
      grommeted group (90%). Grommets alone cannot eradicate inflammation outside the
      middle ear cavity, but rather, they can aggravate it by superinfection. We
      therefore recommend that controlling the radiation-induced inflammation in areas
      such as the ears, nose, sinuses, and nasopharynx is most important. In
      conclusion, post-irradiation OME should be treated in a different way from
      conventional OME. Restated, grommet insertion is contraindicated in post
      irradiation OME.

PMID- 11510733
TI  - Demonstration of intravital microfissures in undecalcified plastic-embedded
      temporal bones with the prestaining technique.
AB  - Microfissures in the human otic capsule have been observed since the start of the
      century, but it was Otto Mayer, in 1930, who first realized that some of them
      were of intravital origin and not just processing artifacts. Since then, a small
      number of publications, based on decalcified temporal bones, have mostly
      confirmed his findings. With the introduction by Frost in the late 1950s of the
      undecalcified bone technique and the bulk staining technique for peripheral
      bones, a method was developed and refined for identifying even very small
      intravital microfissures (microdamage). Bulk staining of undecalcified otic
      capsules has not yet been used to verify the findings from the previous
      decalcified specimens. The present report presents our experience with the
      pertinent techniques, and suggests modifications and shortcuts pertinent to
      temporal bone research. Both large and tiny microfissures of intravital genesis
      are demonstrable within bulk-stained undecalcified human otic capsules. The
      importance of microfissures in the petrous bone in the causation of otosclerosis
      and perilymphatic leakage has long been discussed, and the present techniques may
      advance our understanding of these pathological conditions

PMID- 11510734
TI  - Photochemically induced equilibrium dysfunction in the hamster model with
      evaluation by means of a new globe rotatory test system.
AB  - Thrombosis in the inner ear is regarded as one of the causes of equilibrium
      dysfunction. We have established an experimental thrombosis model by producing a
      photochemical reaction between rose bengal and green light, and have evaluated
      the dysfunction with a new rotatory test system. Hamsters were treated with
      tissue-type plasminogen activator (tPA) in doses of 0, 0.13, 0.26, and 0.52
      mg/kg. The equilibrium dysfunction of the hamsters was evaluated by scoring their
      behavior according to visual observation and by measuring their time on the
      rotatory test system. Treatment of animals with sufficient tPA (> or = 0.26
      mg/kg) caused a significant amelioration of the behavior and a concomitant
      significant prolongation of time on the rotating globe. These findings suggest
      that the equilibrium dysfunction induced by the photochemical reaction was due to
      the thrombi formed, and that our test system may provide a useful tool for
      evaluating equilibrium dysfunction in hamsters.

PMID- 11510735
TI  - Importance of glottic configuration in the development of posterior laryngeal
      granuloma.
AB  - Posterior laryngeal granuloma is frequently related to 3 predisposing factors:
      vocal abuse, gastroesophageal reflux disease, and orotracheal intubation. It is
      strongly predominant in men and rare in women, except under postintubation
      circumstances, in which the incidence is higher in women. The aim of this study
      was to characterize laryngeal conformations for each sex that, whenever
      associated with different causes, may lead to the onset and particular location
      of granulomas, according to a main predisposing factor. Sixty-six subjects whose
      ages ranged from 18 to 73 years were studied. They were distributed into 4 groups
      according to the predominant cause of granuloma: intubation, vocal abuse,
      gastroesophageal reflux, and idiopathic causes. The larynx was evaluated during
      breathing, and the glottic proportion (GP) was measured. Glottic proportion is
      the mathematical ratio between the midsagittal dimension of the intermembranous
      region and that of the intercartilaginous region of the larynx during inhalation.
      Its measurement was feasible in 57 patients. The groups that had a causative
      factor other than laryngeal orotracheal intubation had GP values statistically
      similar to those of each other and to the control group of men, ie, close to 1.2.
      The postintubation group had GP values similar to the control group of women, ie,
      close to 1.0; this proportion protects the arytenoid region in women's larynges
      when there is effort during vocal production, but makes women susceptible to
      orotracheal postintubation granuloma.

PMID- 11510736
TI  - Transillumination laryngoscopy: a new way of evaluating vocal fold and
      hypopharyngeal lesions.
AB  - Conventional methods of observing the larynx and the hypopharynx use reflected
      light to illuminate the larynx. The aim of this study was to see whether
      transilluminating the larynx was possible in subjects with and without disease.
      The larynx and the hypopharynx were observed by means of a rigid scope with a low
      light charge-coupled device camera without the light guide inserted. Illumination
      was provided by a second rigid scope attached to a light source that was held at
      the neck by an assistant. The larynx and hypopharynx were observed by
      transillumination using both constant lighting and stroboscopy in 3 subjects with
      pharyngeal or laryngeal lesions and in 4 normal controls. The tumors were
      translucent or nontranslucent in appearance. A translucent polyp became
      nontranslucent when overlapping the vocal fold, thus indicating that a lesion the
      size of a polyp could be evaluated with this method. Mucosal waves could be
      observed during stroboscopy with transillumination, thus allowing observation of
      waves and lesions that cannot be observed with conventional stroboscopy.

PMID- 11510737
TI  - Comparison of CYFRA 21-1 and squamous cell carcinoma antigen in detecting
      nasopharyngeal carcinoma.
AB  - CYFRA 21-1 is a newly developed tumor marker that is especially useful for
      detecting squamous cell carcinoma (SCC) of the lung. Squamous cell carcinoma
      antigen is a proven tumor marker that is especially useful for detecting SCC of
      the cervix. Our aim in this study was to compare the clinical value of CYFRA 21-1
      and SCC antigen in the detection of nasopharyngeal carcinoma (NPC). Serum levels
      of CYFRA 21-1 and SCC antigen were measured in 80 untreated NPC patients and 77
      healthy controls. The cutoff values of CYFRA 21-1 and SCC antigen, determined at
      the 95th percentile of the 77 healthy controls, were 2.48 ng/mL and 1.49 ng/mL,
      respectively. The results revealed that the mean serum value of only CYFRA 21-1
      was significantly higher in the 80 NPC patients than in the 77 healthy controls,
      and the detection sensitivity of CYFRA 21-1 for NPC was significantly higher than
      that of SCC antigen. In conclusion, our results suggest that CYFRA 21-1 is a
      better tumor marker than SCC antigen for detection of NPC.

PMID- 11510738
TI  - Morphological and histochemical studies of the genioglossus muscle.
AB  - The purpose of this preliminary study was to assess the histo-anatomic
      composition of the genioglossus muscle fibers. The genioglossus muscles were
      obtained from 4 cadavers and 1 autopsy specimen. On morphological study, the
      average diameters of the muscle fibers were seen to gradually increase, from the
      fibers that ran anteriorly to the dorsum of the tongue, to the fibers that ran
      posteriorly to the root of the tongue. Histochemical study revealed that type II
      fibers were significantly predominant in the anterior portion; there was no
      dominant fiber type in the posterior portion. Gradual changes in diameter were
      independent of fiber type. These findings may suggest that the fibers of the
      anterior portion are suitable for phasic action, and that the posterior is
      relatively tonic; and the posterior has larger absolute muscle strength than the
      anterior. It is thought that the fibers of the posterior portion might contribute
      to the maintenance of the mesopharyngeal airway and to vowel production, and that
      the anterior fibers might contribute to some fine movements and to consonant
      production.

PMID- 11510739
TI  - Rhinomanometric and olfactometric variations throughout the menstrual cycle.
AB  - A prospective study was performed to evaluate the rhinomanometric values and the
      changes in the olfactory threshold that occur in women throughout the menstrual
      cycle. The subjects were 60 healthy volunteer premenopausal women 18 to 40 years
      of age. We performed rhinomanometric and olfactometric measurements during the
      follicular, periovular, and luteal phases of the menstrual cycle. Rhinomanometry
      showed a higher (not statistically significant) airflow during the periovular
      phase than during the follicular and luteal phases. Olfactometry showed a higher
      sensitivity during the follicular phase (p < .05) and the periovular phase (p <
      .001) than during the luteal phase. We conclude that airflow and transnasal
      pressure during spontaneous respiration, as well as the olfactory threshold to
      odors, seem to depend on the variations of the ovarian steroids that occur during
      the menstrual cycle.

PMID- 11510740
TI  - Phenytoin-induced lingual tonsil hyperplasia causing laryngeal obstruction.
AB  - The effects of phenytoin sodium on lymphoid tissue have been known for some time.
      However, its effect on the lymphoid tissue of Waldeyer's ring is unreported in
      the otolaryngology literature. We present the case of a 78-year-old woman who was
      treated with phenytoin for generalized tonic-clonic seizures for 4 months and who
      subsequently developed lingual hyperplasia that caused laryngeal obstruction
      eventually requiring a tracheotomy. Of note, no history of airway compromise or
      difficulty with intubation from a prior operation 20 years ago was reported;
      these findings suggest that the lingual tonsillar hyperplasia was a consequence
      of phenytoin therapy and not a preexisting condition. The findings of
      histopathologic evaluation were consistent with lymphoid hyperplasia without
      evidence of malignancy. We also report our operative management and follow-up of
      this rare condition.

PMID- 11510741
TI  - Spontaneous dissection of the internal carotid artery in its extracranial
      portion, revealed by a hypoglossal paralysis: report of four cases.

PMID- 11510742
TI  - Experience with percutaneous dilational tracheostomy.

PMID- 11510743
TI  - Dynamic computer tomography is useful in the differential diagnosis of
      juxtaglomerular cell tumor and renal cell carcinoma.
AB  - We compared dynamic computer tomographic CT images of 3 cases of juxtaglomerular
      (JG) cell tumor with those of 8 cases of renal cell carcinoma (RCC). The JG cell
      tumor was visualized as a low- to high-density area in case 1, a low-density area
      in case 2, and a low- to iso-density area in case 3 before contrast enhancement.
      None of the JG cell tumors were stained during the early phase (1 min), but all
      were stained moderately during the late phase (5 min) after contrast enhancement.
      Although all cases of RCC were visualized as a low- to iso-density area before
      contrast enhancement, they were intensely stained during the early phase with
      significant washout during the late phase. The present results suggest that the
      dynamic CT scan is useful in the differential diagnosis of the JG cell tumor and
      RCC.

PMID- 11510744
TI  - Correlation between fatty liver and coronary risk factors: a population study of
      elderly men and women in Nagasaki, Japan.
AB  - The relation between fatty liver, detected by ultrasonography as a marker of
      visceral fat accumulation, and coronary risk factors was studied in 810 elderly
      men and 1,273 elderly women in Nagasaki, Japan from 1990 to 1992. The prevalence
      of fatty liver was 3.3% in the male and 3.8% in the female non-obese participants
      (BMI, body mass index < 26.0 kg/m2) and 21.6% in the male and 18.8% in the female
      obese participants (26.0 kg/m2 < or = BMI). Fatty liver was significantly (p <
      0.01) related to hypercholesterolemia and hypertriglyceridemia in the men and to
      hypertension, hypercholesterolemia, low-HDL cholesterol, hypertriglyceridemia and
      diabetes mellitus or impaired glucose tolerance (DM+IGT) in the women independent
      of age, obesity, smoking and drinking. Non-obesity with fatty liver, rather than
      obesity with or without fatty liver, had the highest odds ratio for hypertension
      and low-HDL cholesterol in the men and for hypercholesterolemia, low-HDL
      cholesterol, hypertriglyceridemia and DM+IGT in the women. The prevalence of
      fatty liver is the same in elderly men and women, and fatty liver is an
      independent correlate of coronary risk factors in the elderly.

PMID- 11510745
TI  - Transcranial doppler sonography and ambulatory blood pressure monitoring in
      patients with hypertension.
AB  - To appraise the value of transcranial Doppler sonography (TCD) for assessment of
      hypertensive cerebrovascular damage, the relationship between ambulatory blood
      pressure (BP) and indices of cerebral circulation determined by TCD was
      investigated. Subjects were 55 inpatients with or without hypertension, including
      13 patients with histories of cerebrovascular attacks. Mean flow velocity (MFV)
      in the middle cerebral artery was measured by TCD, then the cerebrovascular
      resistance index (CVRI; mean BP/MFV) and the Fourier PI1 (pulsatility index of
      the first Fourier harmonic of the flow-velocity waveform) were determined as
      indices of cerebrovascular resistance. CO2 reactivity of MFV was estimated as an
      index of cerebrovascular flow reserve. CVRI positively correlated with both
      daytime and nighttime BP as well as with age (p<0.01). Fourier PI1 positively
      correlated with nighttime BP and age (p<0.01). CO2 reactivity did not correlate
      with any of the ambulatory BP parameters, but negatively correlated with age
      (p<0.01). LV mass index significantly correlated with ambulatory BP parameters,
      CVRI, and Fourier PI1 but did not correlate with CO2 reactivity. Multiple
      regression analyses showed that nighttime systolic BP was a significant correlate
      for CVRI and Fourier PI1, but not for CO2 reactivity, and that history of
      cerebrovascular attack was significant for CVRI and CO2 reactivity. We conclude
      that cerebrovascular resistance determined by TCD accords with the results of
      ambulatory BP and LVMI, and thus could be successfully used to detect the early
      stage of hypertensive cerebrovascular change. Cerebrovascular flow reserve would
      be relatively preserved in hypertensive patients without cerebrovascular
      diseases.

PMID- 11510746
TI  - A new double cuff sphygmotonometer for accurate blood pressure measurement.
AB  - Accurate measurement of blood pressure (BP) is essential in the diagnosis and
      treatment of hypertension, but neither auscultatory nor oscillometric methods
      measure intra-arterial BP accurately in all circumstances. Algorithms for
      automatic BP-measuring devices differ from manufacturer to manufacturer, and no
      clear authorized algorithm criteria have yet been established. We have devised a
      double-cuff sphygmotonometer to measure BP on the basis of clear algorithms, and
      investigated the accuracy of this new method by comparing it with the photo
      oscillometric method, which is the most accurate method for non-invasive
      measurement of intra-arterial BP. In the new method, a small cuff (3x6 cm)
      replaces the photo-sensor in the brachial cuff (13x24 cm) of the photo
      oscillometric device, and BP is determined by means of the oscillation within the
      small cuff. The comparison based on procedures of AAMI-protocol was performed in
      136 hypertensive patients and 54 normotensive subjects. The difference in
      systolic BP between the photooscillometric and double-cuff methods was -2.26+/
      2.31 mmHg (89% under 5 mmHg), and the corresponding difference in diastolic BP
      was 1.9+/-2.50 mmHg (94% under 5 mmHg). In conclusion, we have devised a new
      double-cuff method which improves on the photo-oscillometric method, and although
      it seems to be less accurate than the photo-oscillometric method, the clarity of
      its algorithm makes it superior to the conventional oscillometric and
      auscultatory methods employing only one cuff.

PMID- 11510747
TI  - Safety and availability of doxazosin in treating hypertensive patients with
      chronic renal failure.
AB  - Hypertension accelerates the progression of renal disease in patients with
      chronic renal failure. Doxazosin, an alpha1-antagonist, is an antihypertensive
      agent with a long half-life. In this study, 15 patients with chronic renal
      failure were treated only with doxazosin and diuretics for 6 months and their
      blood pressure, renal parameters and lipid profile were measured. The initial
      dose of doxazosin was 2 mg/day and it was titrated until blood pressure was
      normalized. The average dose was 5.6 mg/day. As expected, systolic and diastolic
      blood pressure were decreased with treatment (165/91 mmHg to 135/73 mmHg). The
      drop in blood pressure was associated with an increase in glomerular filtration
      and a decrease in plasma BUN and creatinine levels. Reduction in mean blood
      pressure and decrease in proteinuria had a significant positive correlation
      (r=0.048, p=0.007). Proteinuria was decreased from 1.8 mg/day to 1.3 mg/day with
      doxazosin treatment and triglycerides also decreased, while HDL-cholesterol was
      increased. No side effects were observed. These results indicate that doxazosin
      is an efficient depressor agent with renal protective actions and that higher
      doses of doxazosin can be safely given to patients with chronic renal failure.

PMID- 11510748
TI  - The aldehyde dehydrogenase 2 gene is a risk factor for hypertension in Japanese
      but does not alter the sensitivity to pressor effects of alcohol: the Suita
      study.
AB  - Excessive alcohol consumption is a potent risk factor for high blood pressure.
      About half of Japanese show an extremely high sensitivity to alcohol, which is
      due to a genetic deficiency in an isoenzyme of aldehydede-hydrogenase with a low
      Km (ALDH2). It is possible that the effects of alcohol consumption on blood
      pressure differ according to the ALDH2 genotype. The purpose of the present study
      was to assess the influence of the ALDH2 genotype on the pressor effects of
      alcohol. The influence of the ALDH2 genotype on blood pressure was investigated
      in a large cohort (4,000 subjects) representing the general population in Japan.
      The genotype was determined by the TaqMan method. The genotype was significantly
      associated with alcohol consumption, gamma-GTP level, and HDL cholesterol level
      in both males and females. The odds ratio for the presence of hypertension for
      the Glu/Glu genotype in comparison to other genotypes was 1.67 (p< 0.0001, odds
      ratio=1.37-2.08, 95% confidence interval) among males. In contrast, the ALDH2
      genotype had no significant effects on blood pressure among females. To
      investigate whether the ALDH2 genotype affected the sensitivity to the pressor
      effects of alcohol, we analyzed the effects of the ALDH2 genotype
      (Lys/Lys+Lys/Glu=0, Glu/Glu=1) and the level of alcohol consumption on blood
      pressure values after adjusting for age and BMI (residuals after adjusting for
      age and BMI). Among males, while the level of alcohol consumption significantly
      affected systolic, diastolic and pulse pressure, no significant interaction was
      observed between the ALDH2 genotype and the level of alcohol consumption in
      determining blood pressure levels. These results suggest that the Glu/Glu
      genotype is a potent risk factor for hypertension among males mainly through its
      association with the level of alcohol consumption, and that the ALDH2 genotype
      does not affect the sensitivity to the pressor effects of alcohol.

PMID- 11510749
TI  - Differences in mechanisms between weight loss-sensitive and -resistant blood
      pressure reduction in obese subjects.
AB  - This study was conducted to clarify the mechanisms involved in the sensitivity
      for blood pressure (BP) reduction in response to weight loss. In particular, we
      focused on the contributions of sympathetic nervous system activity and fasting
      plasma leptin and insulin levels to BP levels during weight loss in obese
      subjects with weight loss-sensitive and -resistant BP reduction. Sixty-one young,
      obese untreated hypertensive men (HT) and 52 obese normotensive men (NT) were
      enrolled in a weight loss program consisting of a low caloric diet and aerobic
      exercise over a 24-week period. At entry and at week 24, body mass index (BMI),
      BP, plasma norepinephrine (NE), leptin and insulin were measured. Successful
      weight loss and BP reduction were respectively defined as a more than a 10%
      reduction in BMI or mean BP from baseline at week 24. More than 60% of subjects
      in either group successfully achieved weight loss by this definition. The
      percentage of subjects who successfully achieved BP reduction was higher (64%)
      among those subjects who achieved weight loss than among those who did not (22%).
      Plasma NE level at entry in subjects who failed to achieve BP reduction despite
      weight loss was significantly higher than that in subjects who succeeded in BP
      reduction. Plasma leptin and insulin levels were similar between subjects with
      and without BP reduction. In addition, the absolute decrement and percent
      decrement in plasma NE in subjects who succeeded in BP reduction were
      significantly greater than those in subjects who failed to reduce their BP.
      Absolute and percent decrements in plasma leptin and insulin were similar in both
      groups. These results suggest that individuals who are resistant to weight loss
      induced BP reduction have more sympathetic overactivity both at the outset of and
      during weight loss.

PMID- 11510750
TI  - Cilnidipine is as effective as benazepril for control of blood pressure and
      proteinuria in hypertensive patients with benign nephrosclerosis.
AB  - To investigate the beneficial effects of cilnidipine, a calcium channel blocker
      that shows high selectivity for N-type receptors, on the progression of chronic
      renal insufficiency, we compared the efficacy of cilnidipine to that of
      benazepril, an angiotensin-converting enzyme (ACE) inhibitor with known renal
      protective effects, in a one-year trial evaluating hypertensive control, serum
      creatinine, and albuminuria in a cohort of patients. Given the seeming importance
      of the etiology of chronic renal insufficiency in determining drug efficacy, we
      limited our study to 20 patients with a single common condition, benign
      nephrosclerosis. The average age of the patients was 62+/-4 years old. The
      changes in systolic and diastolic blood pressure over the course of the study
      year revealed a similar reduction with cilnidipine and benazepril. Both
      cilnidipine and benazepril induced similar reductions in systolic and diastolic
      blood pressure over the course of the study year. The baseline levels of serum
      creatinine were 1.40+/-0.2 mg/dl and urinary excretion of albumin was 168+/-10 mg
      daily. The levels of serum creatinine were not significantly changed throughout
      the study in either group, although the levels of urinary excretion of albumin
      were significantly decreased in both groups. There were no significant
      differences in either of these values between the two groups. In conclusion, both
      cilnidipine and benazepril equally and effectively reduced blood pressure and
      albuminuria in hypertensive patients with benign nephrosclerosis in a one-year
      trial.

PMID- 11510751
TI  - Two distinct mechanisms of angiotensin II-induced negative regulation of the
      mitogen-activated protein kinases in cultured cardiac myocytes.
AB  - Increasing evidence has suggested that mitogen-activated protein kinases (MAPKs)
      play important roles in the development of cardiac hypertrophy. We and others
      have reported that the activity of MAPKs is tightly regulated by angiotensin II
      (Ang II) in cardiac myocytes. In the present study, we determined the molecular
      mechanism of Ang II-induced inactivation of MAPKs in rat neonatal cardiac
      myocytes. Ang II increased MAPK phosphatase 1 (MKP-1) gene expressions within 10
      min. Levels of MKP-1 transcripts peaked at 30 min and gradually decreased
      thereafter. The increase in MKP-1 mRNA levels was Ang II-concentration dependent.
      An Ang II type 1 receptor (AT1)-specific antagonist, CV-11974, completely
      suppressed the Ang II-induced increase in MKP-1 gene expression, while a type 2
      receptor (AT2)-specific antagonist, PD-123319, had no significant effects.
      Induction of MKP-1 gene expressions by Ang II was inhibited by pretreatment with
      an intracellular Ca2+ chelator, BAPTA-AM, or with the protein kinase C
      inhibitors, H-7 and Calphostin C. Phorbol ester and Ca2+ ionophore both
      significantly increased MKP-1 mRNA levels and showed synergistic action.
      Overexpression of MKP-1 cDNA blocked the Ang II-induced increase in expressions
      of immediate early response genes. In addition, Ang II-induced MAPK activation
      was significantly inhibited by pretreatment with CV-11974, but significantly
      enhanced by pretreatment with PD-123319. Addition of the AT2 agonist, CGP42112A,
      reduced basal MAPK activities, and pretreatment with PD-123319 abolished MAPK
      inactivation by CGP42112A. In conclusion, these observations suggest that Ang II
      negatively regulates MAPKs through AT1 receptors by increasing MKP-1 mRNA levels
      and through AT2 receptors by unknown mechanisms.

PMID- 11510752
TI  - Impaired nitric oxide production and enhanced autoregulation of coronary
      circulation in young spontaneously hypertensive rats at prehypertensive stage.
AB  - In the current study, we investigated the NO-generation pathway in response to
      mechanical stimuli in SHR at the prehypertensive stage. To examine the role of NO
      in coronary autoregulation, we evaluated the effects of L-NAME on the coronary
      flow in SHR at both the prehypertensive and hypertensive stages. Isolated
      perfused hearts from 5- and 15-week-old SHR and from age-matched Wistar-Kyoto
      rats (WKY) were used. After stabilization at 60 mmHg, perfusion pressure was
      immediately raised to 90 mmHg to record the change in coronary flow for 10 min
      without (control) or with NO synthesis blockade by Nomega-nitro-L-arginine methyl
      ester (L-NAME). NOx- (nitrite/nitrate) was measured in coronary effluent. At 5
      weeks of age, SHR did not have hypertension, while the coronary autoregulation
      was enhanced. L-NAME did not affect this enhanced autoregulation in 5-week-old
      SHR. At perfusion pressures of both 60 and 90 mmHg, 5-week-old SHR showed less
      coronary NOx- production than age-matched WKY. At 15 weeks, SHR showed a higher
      blood pressure than WKY. The coronary autoregulation in SHR remained higher than
      that in WKY, but was below that in 5-week-old SHR. NOx- production in 15-week-old
      SHR recovered to the level of age-matched WKY. These results indicate that NOx-
      production induced by mechanical stimulation was markedly reduced in 5-week-old
      SHR at the prehypertensive stage, which may have enhanced coronary
      autoregulation. An impaired nitric oxide production may precede the onset of
      hypertension in SHR.

PMID- 11510753
TI  - Cardioprotection with angiotensin converting enzyme inhibitor and angiotensin II
      type 1 receptor antagonist is not abolished by nitric oxide synthase inhibitor in
      ischemia-reperfused rabbit hearts.
AB  - Although angiotensin converting enzyme (ACE) inhibitor and/or angiotensin II type
      1 (AT1) receptor antagonist can protect the myocardium against ischemia
      reperfusion injury, the mechanisms of the effect have not yet been characterized
      at the cellular level. We here examined the effect of the combination of an ACE
      inhibitor, temocaprilat, an AT1 receptor antagonist, CV-11974 and/or a nitric
      oxide synthase inhibitor, L-NAME, on the myocardial metabolism and contraction
      during ischemia and reperfusion by using phosphorus 31-nuclear magnetic resonance
      (31P-NMR) in Langendorff rabbit hearts. After normothermic 20 min global
      ischemia, postischemic reperfusion of 30 min was carried out. Twenty-one hearts
      were divided into three experimental groups consisting of 7 hearts each: a Tem+CV
      group perfused with a combination of temocaprilat and CV-11974; a Tem+CV+L-NAME
      group perfused with a combination of temocaprilat and CV-11974 plus L-NAME, and a
      control group. During ischemia, both the Tem+CV group and Tem+CV+L-NAME group
      showed a significant inhibition of the decrease in adenosine triphosphate (ATP)
      compared with the control group (p<0.01); the increase in ATP was 50+/-3%, 42+/
      4%, and 19+/-4% in the Tem+CV group, Tem+CV+L-NAME group, and control group,
      respectively. Both experimental groups also showed a significant inhibition of
      the increase in left ventricular end-diastolic pressure (LVEDP) compared with the
      control group (p<0.01). After postischemic reperfusion, the Tem+CV group and
      Tem+CV+L-NAME group again showed a significant improvement of ATP as compared
      with the control group (p<0.01); the increase in ATP was 73+/-3%, 64+/-3%, and
      47+/-4% in the Tem+CV group, Tem+CV+L-NAME group, and control group,
      respectively, and a significant decrease of LVEDP as compared with the control
      group (p<0.01). There were no differences in ATP, or LVEDP during ischemia and
      reperfusion between the Tem+CV group and Tem+CV+ L-NAME group. In conclusion, the
      combination of temocaprilat and CV-11974 showed significant potential for
      improving myocardial energy metabolism and relaxation during both myocardial
      ischemia and reperfusion. This beneficial effect was not dependent on NO
      synthase.

PMID- 11510754
TI  - Altered expression of prostacyclin synthase in a subset of the thick ascending
      limb cells and mesangial cells in 5/6-nephrectomized rats.
AB  - The aim of this study was to evaluate the possible role of prostacyclin (PGl2) in
      the onset and development of hypertension and chronic renal failure in 5/6
      nephrectomized rats (5/6NX). We measured the systolic blood pressure, 24-h
      urinary excretion levels of 6-keto-PGF1alpha, which was a stable metabolite of
      PGI2, and levels of PGI2 synthase (PCS) mRNA in the kidneys. Immunostaining for
      PCS in the kidneys was also evaluated. Systolic blood pressure was higher in
      5/6NX than in sham-operated rats. The 24-h urinary excretion levels of 6-keto
      PGF1alpha in 5/6NX at 1 week postsurgery were lower than in sham-operated rats.
      In renal morphology, tubulointerstitial injury was observed at 2 weeks
      postsurgery, and glomerulosclerosis at 4 weeks. Levels of PCS mRNA in 5/6NX
      decreased significantly at 1 and 2 weeks postsurgery compared with those in sham
      operated rats, but at 8 weeks these levels showed a tendency to increase.
      Immunostaining for PCS was positive in a subset of the cortical thick ascending
      limb of Henle's loop cells, including macula densa in both groups. Moreover, in
      5/6NX at 8 weeks postsurgery, mesangial cells also stained positive for PCS. In
      conclusion, our findings suggest that PCS might play an important role in
      mitigating glomerular hemodynamic changes associated with reduction of renal
      mass.

PMID- 11510755
TI  - Role of nitric oxide in regional blood flow in angiotensin II-induced
      hypertensive rats.
AB  - The present study was designed to evaluate the contribution of nitric oxide (NO)
      to regional hemodynamics during the early phase of angiotensin II (Ang II)
      induced hypertension. The responses of regional blood flow to chronic NO synthase
      inhibition with N(G)-nitro-L-arginine methyl ester (L-NAME) were assessed using
      radioactive microspheres in conscious Ang II-infused hypertensive rats. Ang II
      infused rats (270 ng/kg/min, subcutaneously for 12 days: n=11) showed higher mean
      arterial pressure (MAP: 153+/-4 mmHg) and total peripheral resistance (TPR:
      1.61+/-0.06 mmHg/min/ml), and lower cardiac output (CO: 102+/-3 ml/min) than
      vehicle-infused normotensive rats (115+/-2 mmHg, 0.96+/-0.05 mmHg/min/ml and
      130+/-7 ml/min, n=11, respectively). The blood flow rates in the brain, spleen,
      large intestine and skin were significantly reduced in Ang III-infused rats
      compared with vehicle-infused rats, while those in the lung, heart, liver,
      kidney, adrenal gland, small intestine, and skeletal muscle were similar.
      Treating Ang II-infused rats with L-NAME (75 mg/l in drinking water for 10 days,
      n=11) resulted in higher MAP (166+/-6 mmHg) and TPR (1.89+/-0.18 mmHg/min/ml) and
      lower CO (87+/-7 m/min) than untreated Ang II-infused rats. L-NAME-treated Ang II
      infused rats showed widespread increases in regional vascular resistance and
      reduced blood flow rates in the kidney (3.81+/-0.27 ml/min/g) and skeletal muscle
      (0.20+/-0.03 ml/min/g) compared with untreated Ang II-infused rats (6.88+/-0.27
      and 0.33+/-0.04 ml/min/g, respectively). However, there were no significant
      differences in the flow rates of other organs investigated between these animals.
      An NO donor, (+/-)-(E)-4-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamide (FK409:
      30 microg/kg/min, i.v.), significantly decreased MAP (110+/-6 mmHg) and TPR
      (1.23+/-0.18 mmHg/min/ml) without significant changes in CO (89+/-9 ml/min) in L
      NAME-treated Ang II-infused rats. Furthermore, FK409 partially reversed blood
      flow rates in the kidney (4.72+/-0.40 ml/min/g) and skeletal muscle (0.25+/-0.02
      ml/min/g)in these animals. These results suggest that NO counteracts, at least in
      part, the vasoconstrictor effects of elevated Ang II levels in renal and skeletal
      muscle vascular beds, and is an important modulator in the regulation of blood
      flow to these organs during the development of Ang II-induced hypertension.

PMID- 11510756
TI  - Benidipine dilates both pre- and post-glomerular arteriole in the canine kidney.
AB  - The aim of the present study was to determine the effects of benidipine on renal
      function and whether benidipine may dilate the efferent arteriole as well as the
      afferent arteriole of the canine kidney. The effects of benidipine on the renal
      segmental vascular resistance were estimated using Gomez's formula with some
      modification. The renal hemodynamic action of benidipine was also compared with
      that of amlodipine. Intrarenal arterial injection of benidipine at a dose of 3
      microg/kg resulted in a significant increase in renal blood flow (RBF), urine
      flow and urinary excretion of sodium, but not in glomerular filtration rate
      (GFR). Amlodipine at a dose of 300 microg/kg also increased RBF, urine flow and
      urinary excretion of sodium to a significant degree equivalent to that by
      benidipine. However, in contrast to benidipine, amlodipine significantly
      increased GFR. After the administration of benidipine, autoregulation of RBF and
      GFR was relatively maintained and the renal perfusion pressure (RPP)-RBF relation
      shifted upward; that is, RBFs at 75 and 50 mmHg were maintained at a higher level
      than those of the control. In contrast to benidipine, amlodipine diminished the
      autoregulation of RBF and GFR. RBFs at 75 and 50 mmHg were not different from
      those of the control. The afferent and efferent arteriolar resistance (Ra and Re)
      were calculated based on the RPP-RBF and RPP-GFR relations. Benidipine reduced
      both Ra and Re, but amlodipine selectively reduced Ra. Benidipine increased RBF
      but not GFR via the dilation of both afferent and efferent arterioles. Thus,
      benidipine has unique renal hemodynamic actions which differ from those by most
      calcium antagonists.

PMID- 11510757
TI  - Variables pertinent to the efficiency of adeno-associated virus (AAV) vectors
      mediated gene transfer to human vascular endothelial cells.
AB  - Factors influencing adeno-associated virus (AAV) - mediated gene transfer to
      endothelial cells are not fully determined. We tested the variables pertinent to
      the efficiency of AAV-mediated gene transfer to human vascular endothelial cells
      (HUVEC) including: (i) kinetics of transduction efficiency of LacZ gene to HUVEC,
      (ii) the concentration and volume of vector-containing medium, (iii) the period
      of incubation time of AAV vectors with HUVEC, (iv) the target cell
      density/proliferation, (v) the duration of transgene expression. There is a dose
      response relationship between moi of vectors and transduction efficiency in
      HUVEC. The higher moi of AAV vectors achieved more than 80% of transduction
      efficiency in cultured HUVEC. AAV vectors showed incubation time dependent
      increase in transduction efficiency of LacZ gene to the HUVEC up to 24 h of
      vector exposure. The foreign gene of AAV vectors preferably transduces the lower
      density of cells being proliferated. These results indicate that AAV-vector is
      efficient for gene transfer to HUVEC, and higher moi of vectors or a longer
      period exposure of vectors to proliferating HUVEC can facilitate efficient
      tranduction of foreign gene into human vascular endothelial cells in vitro.

PMID- 11510758
TI  - A family with von Hippel-Lindau disease revealed by pheochromocytoma.
AB  - Von Hippel-Lindau (VHL) disease is an inherited neoplastic disease characterized
      by a predisposition to develop retinal angiomas, central nervous system
      hemangioblastomas, renal cell carcinomas, pancreatic cysts and pheochromocytomas.
      Recently, we encountered three members of the same family who each had both VHL
      disease and pheochromocytoma. As in all three patients we suspected
      pheochromocytoma, the diagnosis of VHL disease should be considered. The possible
      presence of VHL disease was initially investigated in all three patients based on
      the presence of pheochromocytoma. A mutational analysis of the VHL gene revealed
      the presence of a missense mutation, consisting of a G to A transversion, at
      nucleotide 713 in all three patients. This germline point mutation in the VHL
      gene is often detected in type 2 VHL disease with pheochromocytoma. Genetic
      analysis seems to be useful for early detection of VHL disease, even when the
      formal criteria for diagnosis of this disease are lacking.

PMID- 11510759
TI  - Distribution of twenty-four hour urinary taurine excretion and association with
      ischemic heart disease mortality in 24 populations of 16 countries: results from
      the WHO-CARDIAC study.
AB  - There is considerable interest in the association between taurine (2
      aminoethanesufonic acid) and risk of ischemic heart disease (IHD), but little
      information has been made available on the distribution of taurine in populations
      around the world. The present study aimed to describe the differences in taurine
      excretion levels and their associations with IHD mortality rates in 24
      populations in 16 countries worldwide. This was a multicenter cross-sectional
      study. In each center, 100 men and 100 women aged 48-56 years were selected
      randomly from the local populations. Twenty-four hour urinary taurine excretion
      was measured using an amino acid analyzer (Hitachi 835, Ibaragi, Japan). Age
      adjusted IHD mortality rates in the relevant populations were calculated using
      the direct standard method. The results indicated that (a) percentiles 25%, 50%
      and 75% of the distributions of 24-h taurine excretion showed large variations in
      the study populations. Median values of taurine ranged from 191.6 micromol/day
      (St John, Canada) to 2,180.6 micromol/day (Beppu, Japan) in males, and from 127.5
      micromol/day (Moscow, Russia) to 1,590.0 micromol/day (Beppu, Japan) in females.
      The highest overall median value of taurine was found in the Japanese population
      samples, followed by the Chinese samples (Shanghai and Taiwan). European, North
      American and oceanic Caucasians, however, had much lower median values of
      taurine, except in the cases of the samples from France and Spain. (b) Median
      values of taurine were significantly associated negatively with age-adjusted IHD
      mortality rates across the 24 study population samples in men (R2=0.42, p<0.01),
      and in women (R2=0.55, p<0.01). These negative associations remained significant
      after adjustment for serum total cholesterol, body mass index and urinary sodium
      to potassium ratios. In conclusion, the study provides, for the first time, a
      cross-sectional database on distribution of 24-h urinary taurine excretion in 24
      population samples worldwide. A strong and inverse association between population
      levels of taurine excretion and IHD mortality was observed.

PMID- 11510760
TI  - Differences in knowledge, attitude and behavior with respect to hypertension
      among cardiologists, neurologists and other physicians in internal medicine.
AB  - It is known that the knowledge, attitude and behavior (KAB) of physicians with
      respect to hypertension directly affect the prevention of hypertension and
      associated cardiovascular diseases. To investigate the differences in KAB among
      cardiologists, neurologists and other physicians, 1,722 potential participants
      were selected by stratified random sampling. Among these, 1,609 participants took
      part in the present survey, and 948 of this group were eligible for the present
      analysis. The data were collected using a self-administrated questionnaire.
      Results showed that, with respect to knowledge and attitude regarding
      hypertension, 15.3% of cardiologists, 15.2% of neurologists and 7.2% of other
      internals selected the correct answers to all questions (p<0.05). The criteria of
      hypertension were not correctly understood by about two-thirds of physicians,
      including both cardiologists and neurologists. With regard to behavior, 16.5% of
      cardiologists, 17.9% of neurologists and 9.6% of other internals selected the
      correct answers to all questions (p<0.05). A majority of physicians considered
      that routine blood pressure measurements were not necessary in cases
      uncomplicated by cardiovascular disease and other disease, such as nephrotic
      disease, or diabetes mellitus. One-half to two-thirds of physicians did not
      believe that life style modifications reduce blood pressure. For each question,
      cardiologists showed the highest, and other internals the lowest, percentage of
      correct responses to all items in the questionnaire. These findings indicate that
      cardiovascular health education must be strengthened for all physicians, and not
      only for specialists.

PMID- 11510761
TI  - Effects of antihypertensive drugs and gene variants in the renin-angiotensin
      system.
AB  - Many genes and environmental factors are involved in the pathogenesis of
      hypertension, but the exact cause of essential hypertension has not yet been
      clarified. Gene polymorphism of the renin-angiotensin system (RAS) is one of the
      candidates. In the current study, we examined whether there was a correlation
      between the gene polymorphisms in RAS and either the choice of antihypertensive
      drugs or their efficacy. Subjects with essential hypertension (n=299) were
      recruited from among the outpatients of Osaka University Hospital and provided
      their informed consent for genetic analysis. Physicians freely chose the
      antihypertensive drugs and adjusted its dose until the patient's blood pressure
      was well controlled. The efficacy of each antihypertensive drug was estimated
      using the following formula: ABP=BP 1 (before treatment) - BP 2 (after
      treatment)/BP 1 x 100 (%). Gene variants in RAS were determined using PCR or PCR
      RFLP (restriction fragment of polymorphism). The gene polymorphisms of RAS were
      not associated with delta SBP or ADBP. However, the mean ASBP in subjects with a
      deletion homozygote of the angiotensin converting enzyme gene (ACE/DD) was
      significantly lower (p<0.05) than that in patients with an insertion I allele of
      the ACE gene. The gene polymorphisms of RAS did not significantly affect the
      choice of antihypertensive drugs. Even though gene polymorphism in the renin
      angiotensin system was not a major factor in the antihypertensive therapy, the
      determination of genotype might be of help in the management of essential
      hypertension.

PMID- 11510762
TI  - What do we know about gastroesophageal reflux disease?

PMID- 11510763
TI  - The epidemiology of gastroesophageal reflux disease: what we know and what we
      need to know.
AB  - GERD is a common and costly disorder. Despite its prevalence, the epidemiology
      and natural history of GERD are incompletely understood. Until now, most studies
      have been of short duration and utilized convenience samples of patients
      presenting for upper endoscopy. There remain several obstacles, enumerated above,
      that need to be overcome to better study the epidemiology of GERD. Large scale,
      prospective data collection with standardized terminology and longitudinal follow
      up will allow a clearer picture of the incidence, prevalence, natural history,
      and complications of GERD. This in turn should lead to timely, cost-effective
      diagnosis and management of this disorder.

PMID- 11510764
TI  - Critical review of the epidemiology of gastroesophageal reflux disease with
      specific comparisons to asthma and breast cancer.
AB  - GERD is one of the most common GI disorders. Despite its frequent occurrence, the
      absence of a consistent definition and an easily used diagnostic gold standard
      make it difficult to ascertain the true epidemiology of this condition. Recent
      work to validate a short symptom questionnaire to reliably diagnose GERD will be
      a major methodological improvement facilitating the analysis of large populations
      to better define its epidemiology. When these methods are available, a number of
      questions need to be addressed (Table 4). These include elucidating the
      epidemiology of erosive and nonerosive reflux disease, defining the epidemiology
      of GERD among minority populations, determining the natural history of erosive
      and nonerosive reflux disease, and identifying potential risk factors
      contributing to the development of GERD. The answers to these questions should
      improve our understanding of GERD, allowing us to better identify and treat
      individuals and populations at risk with the ultimate goal of improving quality
      of life in addition to preventing the development of GERD complications such as
      adenocarcinoma.

PMID- 11510765
TI  - The role of the specialist in the diagnosis and short and long term care of
      patients with gastroesophageal reflux disease.
AB  - Advances in knowledge about reflux disease and its treatment allow a better
      focused discussion about cost-effective management compared to 5 yr ago. These
      developments also offer opportunities for patient management to be more firmly
      based in a primary care setting, with consequent reductions of cost. This
      opportunity arises from the recognition that endoscopy is an insensitive test for
      reflux disease, and from a more complete understanding of the treatment efficacy
      of proton pump inhibitors. Symptom pattern evaluation and a test of therapy with
      a proton pump inhibitor is now recognized as the best mainstream option for
      diagnosis, and is an approach that is well suited to primary care. Currently,
      though, specialists are more familiar with this, so there is a need for effective
      transfer of these strategies into primary care, along with the message that
      endoscopy will not show any diagnostically reliable changes in more than half of
      patients with troublesome reflux-induced symptoms, though it is the only reliable
      method for recognition of the complications of reflux esophagitis. Most patients
      with troublesome reflux-induced symptoms require long term management, either
      with antireflux surgery or with medication given daily only whenever symptoms are
      troublesome, or in short intermittent courses. The specialist's role in this is
      to advise the patient and his or her primary care doctor as to the available
      options for effective control of reflux disease, with due regard to the costs of
      the therapy and patient preference. The routine delivery of long term medical
      therapy should be in primary care, because there is no need for specialized
      testing or assessment in the course of this treatment.

PMID- 11510766
TI  - Strategies for diagnosis and short and long term treatment: respondent overview.
AB  - Research protocols investigating the value and cost of endoscopy in patients with
      GERD being screened for Barrett's esophagus should be a priority given the
      clinical and economic importance of this issue. Similarly, the cost-effectiveness
      of surveillance of this lesion is also important. The optimal PPI test strategy
      should be determined, as well as the appropriate therapeutic strategy that
      follows. This will need to be determined in each of the clinical presentations of
      GERD, both typical and atypical. Finally, we have almost no information regarding
      appropriate diagnostic and therapeutic strategies of supraesophageal
      manifestations of GERD. Given the enormous health care burden of asthma alone in
      this country, this is obviously an area requiring a high priority for research
      efforts.

PMID- 11510767
TI  - Management of patients with symptomatic gastroesophageal reflux disease: a
      primary care perspective.
AB  - The availability of antacids and over the counter (OTC) histamine 2 (H2) receptor
      antagonists provide ample opportunity for individuals with symptomatic reflux to
      self-medicate before or instead of visiting a physician. Because many patients
      will not achieve complete relief from OTC products, clinicians will be required
      to rethink treatment strategies for those who present with persistent reflux
      symptoms after a trial of low dose H2 receptor antagonists or other
      antisecretories. Patients with persistent heartburn or regurgitation without
      evidence of "alarm symptoms" will usually not require a diagnostic study of the
      upper GI tract. Counseling on lifestyle modifications and empirical antisecretory
      therapy is indicated in most situations. Proton pump inhibitors have consistently
      demonstrated superior symptom relief when compared to H2 antagonists for patients
      with erosive esophagitis and for patients with nonerosive disease. If proton pump
      inhibitors consistently reduce the need for physician visits and diagnostic
      testing, they would seem to be a logical first choice pharmaceutical for
      individuals who fail to improve with OTC H2 antagonists.

PMID- 11510768
TI  - Community issues in gastroesophageal reflux disease: what we know and what we do
      not know.
AB  - GERD is one of the most common disorders seen by physicians. Despite its wide
      prevalence, the impact of this disorder on patients and the community remains
      unclear. A more precise understanding of the impact of GERD on the community will
      require vigorous studies to determine if aggressive diagnosis and therapy improve
      clinical outcomes and decrease the cost of the disease to the community. In
      addition, the issue of screening and surveillance endoscopy for patients with
      long-standing GERD or Barrett's esophagus must be evaluated in terms of the
      ability to decrease esophageal cancer mortality and costs. Comparisons with
      similar diseases, such as asthma and breast cancer, may provide clues to the
      answers to these questions but are not a substitute for rigorous clinical trials.

PMID- 11510769
TI  - Utility and willingness to pay measurements among patients with gastroesophageal
      reflux disease.

PMID- 11510770
TI  - Willingness to pay for improved outcomes in GERD: response to Bernt Kartman.

PMID- 11510771
TI  - Quality of life in patients with gastroesophageal reflux disease.

PMID- 11510772
TI  - Diagnosis and management of gastroesophageal reflux disease in the primary care
      setting: can health-related quality of life play a role?
AB  - Health-related quality of life is a multidimensional construct and patient
      centered outcome that patients value highly. In individuals with untreated GERD,
      multiple studies have demonstrated significant impairment in HRQOL. Treatment
      restores HRQOL to "normal" population levels. In this era of limited health care
      resources, formulary restrictions, and disease management guidelines, a more
      standardized approach to GERD diagnosis and management, through the utilization
      of a GERD-specific symptom rating scale and HRQOL measure(s), may be just what
      the doctor ordered.

PMID- 11510773
TI  - Symptoms of gastroesophageal reflux disease, perceived productivity, and health
      related quality of life.
AB  - OBJECTIVES: To investigate to what extent patients consulting a general
      practitioner (GP) because of symptoms of gastroesophageal reflux disease (GERD)
      report impaired health-related quality of life, absence from work, reduced
      productivity while at work, and reduced daily activities. METHODS: A disease
      specific, self-administered work productivity and activity impairment
      questionnaire (WPAI-GERD) was distributed together with a GERD-specific quality
      of life questionnaire (QOLRAD) and a generic questionnaire (SF-36) to a Swedish
      working population (N = 136) consulting a GP because of current or recent
      symptoms of heartburn. The severity and frequency of GERD symptoms (heartburn and
      acid regurgitation) were recorded by the GP. RESULTS: Among patients with
      heartburn symptoms, a mean of 2.5 h absence from work per week was reported.
      Furthermore, productivity while working was reduced by 23% and productivity while
      doing regular daily activities by 30%. This corresponds to an average of 10.7 h
      lost from work per patient and week, of which 8.3 h are due to reduced
      productivity while working (23% reduction times the actual work time). Results
      from the quality of life questionnaires showed a poor quality of life, especially
      in patients with moderate to severe heartburn symptoms. CONCLUSIONS: In patients
      consulting a GP because of GERD, results indicated that symptoms incur a large
      burden to the patient as well as a considerable cost to society due to absence
      from work, reduced productivity while working, and reductions of regular daily
      activities.

PMID- 11510774
TI  - Employee productivity and gastroesophageal reflux disease: the payer's viewpoint.

PMID- 11510775
TI  - Time trends in cost of caring for people with gastroesophageal reflux disease.
AB  - OBJECTIVE: Increasing acceptance of the many permutations of gastroesophageal
      reflux disease (GERD) has led to diverse study of the disease and its effects.
      The goal of this study was to estimate medical care costs attributable to a
      defined GERD population over time. METHODS: A retrospective cohort control design
      was used. All participants were identified from the database of a managed care
      organization serving 300,000 people in the northeastern United States. The index
      population (n = 600) was defined as anyone who obtained medical services during
      1997 or 1998, for any International Classification of Diseases (ninth revision,
      Clinical Modification) codes suggestive of GERD, and/or anyone who received at
      least one prescription and one refill for antisecretory or GERD medications
      during at least two 3-month periods in 1997 or 1998. A matched cohort (n = 600)
      without any diagnosis of GERD was randomly selected as a control group. Both
      populations were observed restrospectively from January 1, 1990 through December
      31, 1998. RESULTS: The cost of treating GERD averaged around $510 per year, about
      15% of all medical costs for those with GERD. Treating people with GERD was about
      2-fold more costly than treating those without GERD, a marginal cost of $1500 to
      $2000 per annum. CONCLUSION: Although GERD is a low-cost disease to treat, the
      cost of treating people with GERD is subtantially greater than that for a
      comparable population without GERD. Two explanations may account for the large
      difference of costs between the study populations. First, the GERD group may be
      sicker than the control group. Disease severity variables and diagnoses
      associated with GERD were more commonly diagnosed in the GERD group. Second, an
      additional disease that is not treated appropriately increases the cost of
      treatment geometrically for all diseases.

PMID- 11510776
TI  - The employers' perspective on health care costs and the rise in consumerism.

PMID- 11510777
TI  - Resource prioritization in a learning system for health care.

PMID- 11510778
TI  - Endothelins and pulmonary hypertension, what directions for the near future?

PMID- 11510779
TI  - Vascular endothelial growth factor synthesis in the acute phase of experimental
      and clinical lung injury.
AB  - Vascular endothelial growth factor (VEGF) is a potent angiogenic and endothelial
      survival factor, which is abundantly expressed in the normal lung. Conceivably,
      VEGF may be released by numerous cell types found around the airspaces, including
      alveolar type 2 cells, alveolar macrophages, and polymorphonuclear neutrophils.
      Using a bacteria-induced lung injury model in rats, VEGF expression in lung was
      investigated. Both VEGF protein and VEGF messenger ribonucleic acid (mRNA), 4 and
      24 h after bacterial challenge (Pseudomonas aeruginosa), were decreased compared
      with sham rats. VEGF protein was also investigated in bronchoalveolar lavage
      (BAL) from patients studied within 7 days of acute respiratory distress syndrome
      (ARDS) onset and in patients without ARDS. VEGF protein levels in BAL were
      decreased in patients with ARDS versus those without (14.3 +/- 11.1 pg x mL(-1)
      versus 76.8 +/- 51.1 pg x mL(-1), p = 0.03). In aggregate, these findings show
      that the initial phase of acute lung injury is associated with a decrease in
      vascular endothelial growth factor in the lung. This downregulation may represent
      a protective mechanism aimed at limiting endothelial permeability, and may
      participate in the decrease in capillary number that is observed during early
      acute respiratory distress syndrome.

PMID- 11510780
TI  - The effects of pressurization rate on breathing pattern, work of breathing, gas
      exchange and patient comfort in pressure support ventilation.
AB  - The aim of this study was to investigate the effects of different pressurization
      rates during pressure support ventilation on breathing pattern, work of
      breathing, gas exchange and patient comfort in patients with acute lung injury.
      The pressurization rate modifies the initial pressure ramp by changing the
      initial peak flow rate: the increase in pressurization rate is associated with a
      decrease in the time to reach the level of pressure support ventilation by
      increasing the peak flow rate. Ten intubated patients (age 64+/-17 yrs, body mass
      index 24+/-17 Kg x m(-2), arterial oxygen tension/inspired oxygen fraction 214+/
      59) were studied in random order varying the pressurization rate at 5 and 15
      cmH2O of pressure support ventilation. Breathing comfort was evaluated by a
      visual analogue scale. Increasing the pressurization rate caused an increase of
      peak flow rate from 473+/-141 mL x s(-1) to 758+/-302 mL x s(-1) at pressure
      support ventilation 5 (p<0.05) and from 481+/-126 mL x s(-1) to 1,121+/-175 mL x
      s(-1) at pressure support ventilation 15 (p<0.05). At the lowest pressurization
      rate the tidal volume was the lowest, the respiratory rate and the work of
      breathing were the highest (p<0.05) compared with other pressurization rates.
      Excluding the lowest pressurization rate, in all the other pressurization rates
      tested the breathing pattern and the work of breathing did not change. The lowest
      and the highest pressurization rates caused the worst patient comfort (p<0.05).
      The gas exchange was stable throughout the study. The presented results suggest:
      1) the lowest pressurization rate caused the lowest tidal volume, highest
      respiratory rate and highest work of breathing; 2) at the other pressurization
      rates no differences in breathing pattern and work of breathing were observed;
      and 3) the patient's comfort was worse at the lowest and highest pressurization
      rates.

PMID- 11510781
TI  - Human lung fibroblasts secrete nerve growth factor: effect of inflammatory
      cytokines and glucocorticoids.
AB  - Nerve growth factor (NGF) has recently been suggested to contribute to
      inflammation and bronchial hyperresponsiveness in asthma. However, the cell types
      capable of NGF production in the human lung and airways, as well as the
      regulatory role of pro-inflammatory cytokines and of glucocorticoids on NGF
      secretion in pulmonary cells, have not been described. Human pulmonary
      fibroblasts were cultured in the presence or absence of either interleukin-1beta
      (IL-1beta), tumour necrosis factor-alpha (TNF-alpha) and/or glucocorticoids. NGF
      secretion was measured by enzyme-linked immunosorbent assay. The human pulmonary
      fibroblasts constitutively secreted NGF in vitro. The rate of NGF secretion was
      shown to be cell density-dependent, since higher NGF secretion was detected in
      preconfluent cells, i.e. ones with less established cell-to-cell contact (41.0+/
      5.0 pg x 10(-6) cells at 80% confluence), than cells in higher densities (8.2 +/-
      3.4 pg x 10(-6) cells at 100% confluence). Stimulation with the pro-inflammatory
      cytokines IL-1beta (0.3-30 U x mL(-1)) or TNF-alpha (0.1-30 ng x mL(-1)) dose-
      and time-dependently (8-72 h) elevated the NGF secretion (effective concentration
      causing 50% of the maximum response (EC50)=2.9 U x mL(-1) and 1.0 ng x mL(-1),
      respectively). Treatment with the glucocorticoid budesonide (10(-7) M) markedly
      reduced the constitutive secretion of NGF by 42%, and attenuated the cytokine
      stimulated NGF secretion to the same level. In conclusion, human lung fibroblasts
      may serve as a source of nerve growth factor in the lung, positively regulated by
      the asthma-associated and pro-inflammatory cytokines interleukin-1beta and tumour
      necrosis factor-alpha, and negatively regulated by the anti-inflammatory
      glucocorticoids.

PMID- 11510782
TI  - Vitamin E attenuates the injurious effects of bioactive phospholipids on human
      ciliated epithelium in vitro.
AB  - Bioactive phospholipids (PL), particularly lysophosphatidylcholine (LPC), are
      being increasingly implicated in the pathogenesis of various acute and chronic
      inflammatory disorders, particularly those of the airways, while there is
      emerging evidence that vitamin E may function as a natural antagonist of these
      lipid mediators of inflammation. The aims of this study were to document the
      effects of vitamin E on the inhibition of ciliary beating and damage to
      structural integrity of human ciliated epithelium induced by the PL, platelet
      activating factor (PAF), lyso-PAF and LPC in vitro in relation to the anti
      oxidative and membrane-stabilizing properties of the vitamin. Ciliary beat
      frequency was measured by a phototransistor technique, and damage to structural
      integrity assessed by a visual-scoring index, while superoxide production by
      polymorphonuclear leukocytes and membrane-stabilizing potential were measured
      using lucigenin-enhanced chemiluminescence and haemolytic procedures,
      respectively. All three PL caused inhibition of ciliary beating and structural
      damage to human ciliated epithelium by membrane-directed cytotoxic mechanisms,
      which were potentiated by human polymorphonuclear leukocytes due to induction of
      oxidant-mediated injury. Both direct and phagocyte-inflicted epithelial injury
      was attenuated by vitamin E. In haemolytic and chemiluminescence assays, vitamin
      E neutralized both the membrane-destabilizing and pro-oxidative actions of all
      three PL, while spectrophotometric analysis of mixtures of vitamin E with PAF,
      lyso-PAF and LPC revealed alterations in peak intensity, as well as peak shifts,
      indicative of physicochemical interactions between the vitamin and the PL.
      Vitamin E status may be a determinant of susceptibility to phospholipid-mediated
      airway inflammation and damage.

PMID- 11510783
TI  - Expression of members of the phospholipase A2 family of enzymes in human nasal
      mucosa.
AB  - Phospholipase A2 (PLA2) is a family of enzymes thought to play a key role in
      inflammation by releasing arachidonic acid for the synthesis of eicosanoids and
      lysophospholipid for the synthesis of platelet-activating factor. However, the
      precise contribution of different PLA2 types to the formation of inflammatory
      lipid mediators in the upper airways is not known and the expression of different
      PLA2 genes in the human nasal mucosa has not been examined. This study therefore
      investigated the occurrence of messenger ribonucleic acids (mRNAs) for different
      PLA2 forms (IB, IIA, IID, IIE, III, IVA, IVB, IVC, V, VI, VII, X, acid calcium
      independent (aiPLA2), and calcium-independent membrane bound PLA2, (iPLA2-2)) in
      the nasal mucosa of five healthy human subjects. Using reversed transcription
      polymerase chain reaction (RT-PCR) techniques it was found that all these PLA2
      types except PLA2 V were expressed in all subjects, whereas PLA2 V was detected
      in only one individual on one single occasion. The relative abundance of the
      different PLA2 transcripts were aiPLA2 > X approximately = IVA > IIA
      approximately = IIE approximately = IVB approximately = VI > IB approximately =
      IID approximately = III approximately = IVC approximately = VII approximately =
      iPLA2-2. To further quantify the mRNA-expression of PLA2 X, IVA and IIA, the
      samples were reanalysed with a quantitative PCR-technique utilizing competitive
      deoxyribonucleic acid (DNA) mimics as references. The amounts of PLA2 X, IVA and
      IIA mRNA were then estimated to 0.9 +/- 0.2, 1.1 +/- 0.7, and 0.0025 +/- 0.0021
      amol (mean +/- SE), respectively, confirming the relative abundance of these PLA2
      transcripts and indicating that the recently described PLA2 X form is relatively
      strongly expressed. These findings demonstrate that a large number of PLA2 types
      are expressed in the normal human nasal mucosa. Moreover, this investigation
      demonstrates, for the first time, the presence of the newly discovered
      phospholipase A2 forms IID, IIE, III, IVB, IVC, X and calcium-independent
      membrane bound phospholipase A2 in the human nasal mucosa and raises the
      possibility that one or several of these may be involved in inflammatory
      reactions in the nose.

PMID- 11510784
TI  - Fluticasone and salmeterol downregulate in vitro, fibroblast proliferation and
      ICAM-1 or H-CAM expression.
AB  - Beta2-adrenoreceptor agonists have pharmacological properties that may suggest an
      inhibitory effect on various aspects of the inflammatory and repair processes
      that characterize asthma. Since fibroblasts express beta2-adrenoreceptors, the
      effects of different concentrations (0.1-100 nM) of fluticasone propionate (FP),
      salmeterol (S) and their combination (FP+S) on lung fibroblast proliferation and
      adhesion molecule expression were evaluated. Stimulation of human foetal lung
      fibroblasts with a fibrogenic cytokine, basic fibroblast growth factor (bFGF),
      resulted in a [methyl-3H] thymidine ([3H]TdR) uptake, four-fold higher than that
      of control cultures (p=0.0001) and was significantly inhibited by S, at all the
      concentrations tested (0.1-100 nM; p<0.05). No changes in bFGF-induced cell
      proliferation were observed in the presence of FP (0.1-100 nM; p>0.05, all
      comparisons). In addition, the association FP+S did not improve the inhibitory
      activity of S alone (p>0.05, each comparison). An upregulation of intercellular
      adhesion molecule-1 (ICAM-1) expression was induced by tumour necrosis factor
      alpha (TNF-alpha) (p=0.0004), but not by interleukin-4 (IL-4) (p>0.05), while
      none of the two cytokines were able to increase hyaluronic-cellular adhesion
      molecule (H-CAM) expression by lung fibroblasts (p>0.05). A significant
      downregulation of ICAM-1 or H-CAM expression was demonstrated in the presence of
      FP or S, at all concentrations tested (0.1-100 nM; p<0.01, each comparison).
      Interestingly, S (10 nM and 100 nM) was able to enhance the inhibitory activity
      of FP on ICAM-1 expression (p<0.01), but not on H-CAM expression (p>0.1). These
      results show that in human foetal lung fibroblasts, fluticasone propionate and
      salmeterol are effective in modulating in vitro, different lung fibroblast
      biological functions that are likely to be involved in airway remodelling.

PMID- 11510785
TI  - Herpesvirus type 1-8 in BAL fluid from HIV-1-infected patients with suspected
      pneumonia and from healthy individuals.
AB  - Pneumonia is still a major problem in human immunodeficiency virus (HIV)-infected
      patients, and despite extensive investigation the aetiology remains unknown in
      many cases. The prevalence of the eight human herpesviruses was determined by
      polymerase chain reaction in 91 samples of bronchoalveolar lavage (BAL) fluid
      from 72 HIV-infected patients with 91 episodes of suspected pneumonia. The
      presence of herpesviruses was related to clinical and immunological findings and
      the prevalence of herpesviruses in HIV-infected patients was compared with the
      prevalence in BAL fluid from 50 healthy, immunocompetent individuals. Epstein
      Barr virus, cytomegalovirus and human herpesvirus-8 (HHV8) were found in 5.5%,
      36% and 5.5% of BAL fluid samples from HIV-infected patients. No herpesviruses
      were detectable in BAL fluid from healthy, immunocompetent individuals. The
      herpesviruses occurred mainly in patients with CD4+ counts <200 x 10(6) L(-1).
      All patients with herpesviruses recovered without specific antiviral treatment.
      Two patients with HHV8 had the diagnosis of Kaposi's sarcoma. It is concluded
      that cytomegalovirus, Epstein-Barr virus, and human herpesvirus-8 are frequently
      present in bronchoalveolar lavage fluid from severely immunocompromised human
      immunodeficiency virus-infected patients with pulmonary symptoms. In
      bronchoalveolar lavage fluid from healthy, immunocompetent individuals,
      herpesviruses are absent. Apart from human herpesvirus-8, the present results
      indicate that the herpesviruses do not play a serious pathogenic role in the
      development of pulmonary symptoms in human immunodeficiency virus-infected
      patients.

PMID- 11510786
TI  - Aerosolized PGE1, PGI2 and nitroprusside protect against vascular leakage in lung
      ischaemia-reperfusion.
AB  - High permeability oedema is an important feature in lung injury secondary to
      ischaemia-reperfusion. This study investigated the influence of aerosolized
      prostaglandin E1 (PGE1), prostaglandin I2 (PCI2) and the nitric oxide (NO)-donor,
      sodium nitroprusside (SNP) on microvascular barrier function in pulmonary
      ischaemia-reperfusion. Buffer-perfused rabbit lungs were exposed to 180 or 210
      min of warm ischaemia while maintaining anoxic ventilation and a positive
      intravascular pressure. Reperfusion provoked a transient, mostly precapillary
      elevation of vascular resistance, followed by a severe increase of the capillary
      filtration coefficient (Kfc) versus nonischaemic controls (3.17+/-0.34 versus
      0.85+/-0.05 cm3 x s(-1) cmH2O(-1) x g(-1) x 10(-4) after 30 min of reperfusion),
      and progressive oedema formation. Short-term aerosolization of SNP, PGE1 or PGI2
      at the beginning of ischaemia largely suppressed the Kfc increase (1.36+/-0.22,
      1.32+/-0.23 and 1.32+/-0.22 cm3 x s(-1) x cmH2O(-1) x g(-1) x 10(-4),
      respectively) and oedema formation. In contrast, application prior to reperfusion
      was much less effective, with some reduction of Kfc increase by PGI2 and SNP and
      no effect of PGE, (1.79+/-0.31, 2.2+/-0.53 and 3.2+/-0.05 cm3 x s(-1) x cmH2O(-1)
      x g(-1) x 10(-4), respectively). Haemodynamics, including microvascular pressure,
      were only marginally affected by the chosen doses of aerosolized vasodilators. It
      is concluded that short-term aerosolization of prostaglandin E1, prostaglandin I2
      and sodium nitroprusside at the onset of ischaemia is highly effective in
      maintaining endothelial barrier properties in pulmonary ischaemia-reperfusion.
      This effect is apparently attributable to nonvasodilatory mechanisms exerted by
      these agents. Alveolar deposition of prostaglandins and/or nitric oxide donors by
      the aerosol technique may offer pulmonary protection in ischaemia-reperfusion
      injury.

PMID- 11510787
TI  - Initial risk class and length of hospital stay in community-acquired pneumonia.
AB  - The total medical costs of community-acquired pneumonia are directly related to
      the costs of hospital admission and length of stay. The aim of the present study
      was to evaluate the reasons for prolonged duration of stay in patients stratified
      in five risk classes for death, and to identify factors associated with prolonged
      stay. The study population consisted of 295 patients. According to lower (classes
      I, II, III) or to higher (classes IV, V) risk, the target duration of
      hospitalization was set at 5 and 7 days, respectively. The causes of prolonged
      hospitalization were classified as pneumonia-related, complications, unstable
      comorbid diseases and nonclinical factors. The overall percentage of patients
      with appropriate duration of hospitalization was 32%. Causes of prolonged
      hospitalization were related mainly to pneumonia (32%) from all risk classes.
      Morbid complications and instability of the underlying illness were greater in
      class V patients. Nonclinical factors were present in 29.5% of cases. Hypoxaemia,
      anaemia, hypoalbuminaemia, and complications appearing before 72 h were
      associated with prolonged hospitalization. The cause of prolonged hospitalization
      of patients with community-acquired pneumonia is multifactorial, depending mainly
      on pneumonia and comorbid conditions but there is a large number of unnecessary
      hospitalization days that could be reduced by improving the efficiency of
      hospital care.

PMID- 11510788
TI  - Diagnosis of nosocomial pneumonia in medical ward: repeatability of the protected
      specimen brush.
AB  - The aims of this study were to assess the repeatability of two pairs of protected
      specimen brushes (PSB) done successively in the same lung area and either
      processed at the bedside or in the laboratory, and to provide a description of
      the bacteriological findings in 39 cases of suspected nosocomial pneumonia
      occurring in nonventilated patients. Four PSB were divided into two pairs. One
      pair of brushes (PB) was prepared at bedside and then sent to the laboratory; the
      other pair (PL) was immediately sent to the laboratory for complete processing.
      According to a 10(3) colony forming units (cfu) x mL(-1) threshold, 49% out of
      156 PSB were positive. Using the 10(3) cfu x mL threshold, the PL brushes were
      89.7% concordant while the PB brushes were 76.9% concordant. The repeatability as
      expressed by K-value of the cultures of PSB was higher for PL brushes than for PB
      brushes (K-values of 0.795 and 0.537 respectively, p=0.12). Bacterial species
      were isolated in 58.3% of 156 PSB (176 isolates). In 14 cases, cultures of PSB
      disclosed more than one micro-organism in a concentration > 10(3) cfu x mL(-1).
      The most frequently isolated organisms were Pseudomonas spp. (23.9%),
      Enterobacteriaceae (23.3%), Streptococcus spp. (21.6%) and Staphylococcus spp.
      (13.1%). Polymicrobial cultures were more frequent if the patient had a
      tracheostomy (seven out of the nine patients with a tracheostomy versus seven out
      of the 30 patients without a tracheostomy, p<0.01). Bacteriological discrepancies
      leading to a potential troublesome choice in antibiotherapy were observed in
      31.8% of the patients for PL brushes and 56.5% of the patients for PB brushes.
      There is a low degree of repeatability of protected specimen brushes outside
      intensive care units which seem dependent on sampling processing. The
      distribution of pathogens found in case of suspicion of nosocomial pneumonia in
      nonventilated patients appears to be similar to that obtained in ventilator
      associated pneumonia.

PMID- 11510789
TI  - Total energy expenditure in children with obstructive sleep apnoea syndrome.
AB  - Childhood obstructive sleep apnoea syndrome (OSAS) acts as a check on growth and
      nutritional status. An increase in sleeping energy expenditure has been proposed
      as a possible mechanism, but to date, no studies have determined whether energy
      requirements (total energy expenditure; TEE) are raised in OSAS. The aim of this
      study was to test the hypothesis that OSAS is associated with increased TEE.
      Eleven children (mean+/-SD 5.8+/-2.2 yrs of age) with OSAS confirmed by nocturnal
      polysomnography were each matched with a pair of healthy controls (n=22) of the
      same age and sex. TEE was measured using the doubly-labelled water method in all
      subjects. In 10/11 patients TEE was also measured after adenotonsillectomy and
      changes in TEE assessed. There was no significant difference in TEE between
      patients (mean+/-SD 325+/-44 kJ x kg(-1) x day(-1)) and controls (339+/-48 kJ x
      kg(-1) x day(-1)), nor between patients and age- and sex-specific literature data
      on TEE, using the doubly-labelled water method. Differences in TEE within
      patients, before versus after surgery, were minor and not statistically
      significant. This study does not support the hypothesis that obstructive sleep
      apnoea syndrome in childhood is associated with increased energy requirements,
      and suggests that alternative explanations for the effect of this syndrome on
      growth and energy balance should be sought.

PMID- 11510790
TI  - Importance of sleep stage- and body position-dependence of sleep apnoea in
      determining benefits to auto-CPAP therapy.
AB  - The influence of sleep stage- and body position-dependence of sleep apnoea on
      treatment efficacy and compliance between conventional continuous positive airway
      pressure (CPAP) and auto CPAP therapy was evaluated. Thirty-three newly treated
      sleep apnoea hypopnoea syndrome (SAHS) patients were randomly allocated to
      conventional or auto-CPAP therapy. Six patients of each treatment group were
      classified as having sleep stage- and body position-dependent obstructive
      breathing abnormalities according to the results of the baseline sleep study.
      After 3 weeks of treatment, the Epworth sleepiness score tended to be higher (p =
      0.08) and the ability to stay awake lower (p = 0.02) in patients with dependent
      breathing abnormalities treated with fixed CPAP, than in the other patients. The
      effective pressure/time index was significantly lower in sleep stage- and body
      position-dependent patients treated with fixed CPAP, than in the other patients
      (p = 0.02). The number of hours the machine was turned on and a positive pressure
      applied, tended to be smaller in dependent patients treated with fixed CPAP than
      in independent patients of this treatment group and in patients treated with auto
      CPAP. A night-to-night variability index (VI) of positive pressure changes was
      obtained in the auto-CPAP group. This index significantly decreased with time in
      the dependent patients while it remained unchanged in the independent group. It
      is concluded that auto-continuous positive airway pressure may have specific
      indications in a subset of obstructive sleep apnoea patients with sleep stage-
      and body position dependent nocturnal breathing abnormalities.

PMID- 11510791
TI  - EGTA treatment of human airways in vitro unmasks M1/MUC5AC mucin in submucosal
      glands.
AB  - Mucin staining can be used to evaluate secretory activity of human airways.
      However, mucin epitopes may be masked by physicochemical properties of the
      secretions. The aim of this investigation was to examine the effects of the
      calcium chelator, ethyleneglycol-bis-(beta-aminoethylether)-N,N,N',N'-tetraacetic
      acid (EGTA) on the detection of M1/MUC5AC mucin in isolated human bronchial
      preparations. Immunohistochemical investigation and immunoradiometric assays with
      anti-M1 monoclonal antibodies (Mabs) were used to detect M1/MUC5AC mucin derived
      from bronchial preparations with an intact surface epithelium, or in tissues
      where the epithelium had been removed (rubbed preparations). The Mabs labelled
      both epithelial goblet cells and submucosal glandular cells in EGTA (4 mM)
      exposed bronchial preparations, while only goblet cells were stained in EGTA (0.4
      mM)-exposed tissues. The quantities of M1/MUC5AC mucin detected in either the
      bronchial fluids derived from EGTA (4 mM)-exposed intact and rubbed preparations
      or in bronchial fluids treated with EGTA (4 mM) were significantly increased by
      two-fold when compared with untreated control values (p<0.001). In addition,
      lactate dehydrogenase (LDH) activity and protein measurements were unaltered
      during exposure of human airways to EGTA (4 mM) suggesting that this treatment
      did not affect tissue viability. These results provide evidence that
      ethyleneglycol-bis-(beta-aminoethylether)-N,N,N',N'-tetraacetic acid (4 mM)
      facilitates the detection of M1/MUC5AC mucin by altering the physicochemical
      properties of respiratory mucin, thereby exposing epitopes with which anti-M1
      monoclonal antibodies are reactive. This will allow more accurate measurement of
      secretory activity in human airways in vitro.

PMID- 11510792
TI  - Pneumococcal vaccination: current and future issues.
AB  - Infection with Streptococcus pneumoniae remains a major global health burden
      meaning the development of effective vaccines is urgently needed. The current 23
      valent polysaccharide vaccine has been shown to prevent pneumococcal pneumonia in
      immunocompetent young adults, but not in elderly persons. However, in prevention
      of invasive pneumococcal disease, the vaccine is efficacious in the elderly and
      may also be effective in some groups of immunocompromised patients. The
      polysaccharide vaccine is, therefore, recommended in all older (> or = 55-65 yrs
      of age) adults and in young children (>2 yrs of age) who have a high risk for
      pneumococcal disease. Revaccination can be safely performed and is recommended 5
      yrs after the first dose. In children <2 yrs of age, the new polysaccharide
      protein conjugate vaccines, including 7-11 serotypes, seem to be effective in the
      prevention of invasive disease, severe pneumonia and serotype-specific (and
      vaccine-related types) otitis media. The low serotype coverage, need for repeated
      doses, and high price, may decrease the usefulness of the new conjugates.
      However, the included serotypes correspond to those most often associated with
      penicillin resistance and vaccination is, therefore, a possible tool in limiting
      the spread of antibiotic-resistant pneumococci.

PMID- 11510793
TI  - Imaging of pneumonia: trends and algorithms.
AB  - Pneumonia is one of the major infectious diseases responsible for significant
      morbidity and mortality throughout the world. Imaging plays a crucial role in the
      detection and management of patients with pneumonia. This review article
      discusses the different imaging methods used in the diagnosis and management of
      suspected pulmonary infections. The imaging examination should always begin with
      conventional radiography. When the results of routine radiography are
      inconclusive, computed tomography is mandatory. A combination of pattern
      recognition with knowledge of the clinical setting is the best approach to the
      pulmonary infectious processes. A specific pattern of involvement can suggest a
      likely diagnosis in many instances. In acquired immune deficiency syndrome
      patients, diffuse ground-glass and interstitial infiltrates are most commonly
      present in Pneumocystis carinii pneumonia whereas in the nonimmunosuppressed
      patients, a segmental lobar infiltrate is suggestive of a bacterial pneumonia.
      Round pneumonia is most often encountered in children than adults and is most
      often caused by Streptococcus pneumoniae. Different combinations of parenchymal
      and pleural abnormalities may be suggestive for additional diagnoses. When an
      infectious pulmonary process is suspected, knowledge of the varied radiographic
      manifestations will narrow the differential diagnosis, helping to direct
      additional diagnostic measures, and serving as an ideal tool for follow-up
      examinations.

PMID- 11510794
TI  - Noninvasive mechanical ventilation in acute hypoxaemic respiratory failure.
AB  - In acute hypoxaemic respiratory failure (HRF), oxygenation, reduction in the work
      of breathing and in dyspnoea may be achieved by delivering noninvasive mechanical
      ventilation (NIMV). Several uncontrolled and 13 randomized controlled studies
      (RCS) were reviewed. Uncontrolled studies confirmed the feasibility and the
      possibility to improve arterial blood oxygenation with NIMV. The 13 RCS compared
      NIMV versus a conventional approach in a total of 720 patients with HRF.
      Endotracheal intubation was required in 186 of the 358 patients (median (95%
      confidence interval (CI)) 51%, (40-63%)) assigned to a conventional approach and
      in 107 of the 362 patients (29% (20-39%)) assigned to NIMV. Eleven of the 13 RCS
      found a reduction in the rate of endotracheal intubation with NIMV with an
      absolute risk reduction of 31% (30-33%). Ten of the 13 RCS found a reduction in
      the mortality rate which was 30% (19-40%) in the control group and 19% (13-26%)
      in the NIMV group. The mean absolute risk reduction was 15% (10-20%). In
      conclusion, noninvasive ventilation appears to be a useful method in avoiding
      endotracheal intubation and probably in reducing the morbidity of patients with
      hypoxaemic respiratory failure.

PMID- 11510795
TI  - Molecular physiology of oxygen-sensitive potassium channels.
AB  - Physiological adaptation to acute hypoxia involves oxygen-sensing by a variety of
      specialized cells including carotid body type I cells, pulmonary neuroepithelial
      body cells, pulmonary artery myocytes and foetal adrenomedullary chromaffin
      cells. Hypoxia induces depolarization by closing a specific set of potassium
      channels and triggers cellular responses. Molecular biology strategies have
      recently allowed the identification of the K+ channel subunits expressed in these
      specialized cells. Several voltage-gated K+ channel subunits comprising six
      transmembrane segments and a single pore domain (Kv1.2, Kv1.5, Kv2.1, Kv3.1,
      Kv3.3, Kv4.2 and Kv9.3) are reversibly blocked by hypoxia when expressed in
      heterologous expression systems. Additionally, the background K+ channel subunit
      TASK-1, which comprises four transmembrane segments and two pore domains, is also
      involved in both oxygen- and acid-sensing in peripheral chemoreceptors. Progress
      is currently being made to identify the oxygen sensors. Regulatory beta subunits
      may play an important role in the modulation of Kv channel subunits by oxygen.

PMID- 11510796
TI  - European Respiratory Society Guidelines on the use of nebulizers.

PMID- 11510797
TI  - A model of viral wheeze in nonasthmatic adults: symptoms and physiology.
AB  - Episodic wheezing associated with viral infections of the upper respiratory tract
      (URT) is a common problem in young children but also occurs in adults. It is
      hypothesized that an experimental infection with human coronavirus (HCoV), the
      second most prevalent common cold virus, would cause lower respiratory tract
      (LRT) changes in adults with a history of viral wheeze. Twenty-four viral
      wheezers (15 atopic) and 19 controls (seven atopic) were inoculated with HCoV
      229E and monitored for the development of symptoms, changes in airway physiology
      and provocative concentration of methacholine causing a 20% fall in forced
      expiratory volume in one second (FEV1) (PC20). At baseline, viral wheezers were
      similar to controls in PC20 (mean+/-SD log2PC20: 5.1+/-1.9 and 5.8+/-1.4 g x L(
      1), respectively) but had a lower FEV1 than controls (mean+/-SD 85.8+/-11.4 and
      95.6+/-13.2% predicted, respectively p < 0.05). Nineteen viral wheezers and 11
      controls developed colds. Viral wheezers with colds reported significantly more
      URT symptoms than controls (median scores (interquartile range): 24 (10-37) and 6
      (4-15), respectively p = 0.014). Sixteen viral wheezers and no controls reported
      LRT symptoms (wheeze, chest tightness and shortness of breath). The viral
      wheezers with colds had small (3-4%) reductions in FEV1 and peak expiratory flow
      on days with LRT symptoms (days 3-6), but a progressive reduction in PC20 from
      baseline on days 2, 4 and 17 after inoculation (by 0.82, 1.35 and 1.82 doubling
      concentrations, respectively). The fall in PC20 affected both atopic and
      nonatopic subjects equally. There were no changes in FEV1 or PC20 in controls. An
      adult model of viral wheeze that is independent of atopy and therefore, of
      classical atopic asthma was established.

PMID- 11510798
TI  - Acute lung injury associated with 5-fluorouracil and oxaliplatinum combined
      chemotherapy.
AB  - Diarrhoea, T-CD4+ lymphopenia and bilateral patchy pulmonary infiltrates
      developed in a male 60 yrs of age, who was treated with oxaliplatinum and 5
      fluorouracil for unresectable rectum carcinoma. The findings from transbronchial
      lung biopsy and bronchoalveolar lavage (BAL) were consistent with an organizing
      diffuse alveolar damage pattern. Once extensive microbiological studies proved
      negative, corticosteroids were given and a complete remission of clinical and
      radiological abnormalities was achieved. It is concluded that the aforementioned
      pathological manifestations were due to chemotherapy and included a pulmonary
      adverse reaction, a feature never previously associated with oxaliplatinum and 5
      fluorouracil regimens.

PMID- 11510799
TI  - Systemic bioavailability of inhaled corticosteroids: appropriate and comparable
      methodology.

PMID- 11510800
TI  - Long-term treatment of pulmonary hypertension with aerosolized iloprost.

PMID- 11510801
TI  - Clinical management of asthma in 1999: the Asthma Insights and Reality in Europe
      (AIRE) study.

PMID- 11510802
TI  - Changes in fatal and near-fatal asthma in an urban area of South Africa from 1980
      1997.
AB  - Over the past two decades, changes in the health services designed to improve
      access to and quality of asthma care have occurred in South Africa. The aim of
      this study was to investigate the incidence of fatal and near-fatal asthma (NFA)
      from 1980-1997 in an urban part of South Africa. A retrospective analysis of
      fatal asthma and NFA in the Cape Town City Council area was performed. Mortality
      data were obtained from death notification records. Data on NFA were obtained
      from the records of patients admitted for asthma to intensive care units (ICUs)
      at major academic hospitals serving the area. There were 1,506 deaths (mean age
      56 yrs) from asthma reported; 39 and 3% occurred in people under 55 and 15 yrs,
      respectively. Average annual asthma mortality rate (8.1 +/- 1.9 per 100,000
      population) was highest amongst people of mixed race (10.1 +/- 2.0), followed by
      Blacks (6.8 +/- 3.1) and Whites (5.0 +/- 1.9, p<0.001). Asthma mortality declined
      by 0.28 deaths per 100,000 population per year; rates decreased in all ethnic
      groups. Most deaths (72.3%) were outside a health facility and a higher number of
      deaths occurred on weekends (223 deaths x day(-1)) than weekdays (207 deaths x
      day(-1), p=0.014). Paediatric asthma ICU admissions declined by 1.81 children yr(
      1). The annual number of adults admitted to ICU for asthma, and the proportion
      requiring intermittent positive pressure ventilation did not change. These
      results indicate that the incidence of fatal and near-fatal asthma in this area
      has declined over the period and this may reflect improved asthma management.
      However, the relatively high asthma mortality rate in people of mixed race and
      the predominance of deaths outside health facilities and on weekends suggest
      problems with access to care.

PMID- 11510803
TI  - Comparison of the standard gamble, rating scale, AQLQ and SF-36 for measuring
      quality of life in asthma.
AB  - With interest in health economics growing, there is a demand for valid methods
      for measuring health-related quality of life (HRQL) in asthma using utilities.
      The aims of this study were to develop disease-specific versions of the standard
      gamble and rating scale, to compare their measurement properties with those of
      the Asthma Quality of Life Questionnaire (AQLQ) and the Medical Outcomes Survey
      Short-Form 36 (SF-36), as well as to determine their validity for assessing
      asthma-specific quality of life. Forty adults with symptomatic asthma
      participated in a 9-week observational study. Participants completed the standard
      gamble, rating scale, AQLQ, SF-36 and other measures of clinical asthma status at
      baseline and after 1, 5 and 9 weeks. In patients whose asthma was stable between
      assessments, reliability was good for the rating scale (intraclass correlation
      coefficient (ICC)=0.89) and the AQLQ (ICC=0.95) but more modest for the SF-36
      mental score (ICC=0.68), SF-36 physical score (ICC=0.65) and standard gamble
      (ICC=0.59). The responsiveness index was highest in the AQLQ (1.35), followed by
      the rating scale (0.74), the physical score of the SF-36 (0.61) and the standard
      gamble (0.31). Construct validity (correlation with other indices of health
      status) was strongest for the AQLQ and the rating scale. In conclusion, both the
      disease-specific rating scale and the Asthma Quality of Life Questionnaire have
      strong measurement properties for measuring asthma-specific quality of life; the
      Short-Form 36 health survey physical summary score has more modest properties.
      Although the disease-specific standard gamble has acceptable discriminative
      properties, its evaluative properties are too inadequate for it to be used in
      cost/utility analyses. Poor correlation between the standard gamble and the
      rating scale indicates that utilities cannot be derived from rating scale data.

PMID- 11510804
TI  - The effects of an anti-CD4 monoclonal antibody, keliximab, on peripheral blood
      CD4+ T-cells in asthma.
AB  - CD4+ T-cells are likely to be involved as a source of pro-inflammatory cytokines
      in asthma. This study assessed the effects of an infusion of keliximab (IDEC
      CE9.1), an anti-CD4+ monoclonal antibody, on peripheral blood CD4+ T-cells in
      corticosteroid-dependent asthmatics. Three cohorts of patients (termed C0.5: n=6,
      C1.5: n=5, and C3.0: n=5) received a single infusion of 0.5, 1.5 or 3.0 mg x kg(
      1), respectively, with a fourth receiving placebo (Cpl: n=6), and were followed
      up for 4 weeks. By flow cytometry in peripheral blood, pre- and postinfusion
      assessment was made of: a) CD4 and CD8 counts and mean fluorescence; b) CD25,
      human leukocyte antigen-DR (HLA-DR), CD45RO and CD45RA expression on CD4+ T
      cells; and c) interferon (IFN)-gamma, interleukin (IL)-4 and IL-5 expression in
      CD4+ T-cells. Keliximab's in vitro effects on allergen-specific peripheral blood
      mononuclear cells (PBMC) proliferation in atopic asthmatics were also evaluated.
      There was a significant increase in lung function (peak expiratory flow rate) in
      the C3.0 group. Following infusion in C0.5, C1.5 and C3.0 but not Cpl: 1) the
      CD4, but not CD8 count was significantly decreased; 2) there was total loss of
      Leu3a staining; 3) there were significant reductions in the mean fluorescence of
      OKT4 binding; and 4) there were significant reductions in the numbers of CD25,
      HLA-DR, CD45RO and CD45RA/CD4+ cells. There were no changes in CD4+ cell
      expression of IFN-gamma, IL-4 or IL-5. Keliximab caused a significant reduction
      in T-cell proliferation as compared to a control monoclonal antibody. Keliximab,
      as an anti-CD4 monoclonal antibody, leads to a transient reduction in the number
      of CD4+ T-cells and modulation of CD4+ receptor expression in severe asthmatics.
      The effects of keliximab may be mediated through a decrease in CD4+ surface
      expression and T-lymphocyte numbers, in addition to a reduction in allergen
      induced proliferation.

PMID- 11510805
TI  - Discrepant distribution of big endothelin (ET)-1 and ET receptors in the
      pulmonary artery.
AB  - Since pulmonary vasculature is complex in terms of regional difference in
      structure and function, it is important to understand the site of endothelin (ET)
      synthesis and the distribution of the ET system along the axial pathways of
      pulmonary artery. The expression of big ET-1, ET converting enzyme (ECE) and
      ET(A) receptors were examined in rat pulmonary arteries under normal and hypoxic
      conditions using an immunohistochemical method and Northern blot analysis. In
      normal conditions, big ET-1 was expressed in the intima and media of pulmonary
      arteries with a predominant distribution in the distal segments and a
      preferential localization in the media, while ETA receptors were dominantly
      expressed in the proximal segments. ECE was constitutively expressed in the
      intima and media. Following exposure to hypoxia, messenger ribonucleic acid
      (mRNA) expression of ET-1 and ET(A) receptors were up-regulated by two-fold and
      immunoreactivities for big ET-1, ECE, and ET(A) receptors significantly increased
      by two to five-fold in the distal segments. Smooth muscle cells are an important
      source of endothelin-1 in the pulmonary artery. The distribution of big
      endothelin-1 and endothelin A receptors in pulmonary arteries was discrepant in
      normal conditions while their expression concomitantly increased in the distal
      segments in hypoxic conditions. This heterogeneity may play an important role in
      the regulation of pulmonary vascular tone.

PMID- 11510806
TI  - The voluntary drive to breathe is not decreased in hypercapnic patients with
      severe COPD.
AB  - How do the respiratory centres of patients with chronic obstructive pulmonary
      disease (COPD) and hypercapnia respond to acute increases in inspiratory load? A
      depressed respiratory motor output has long been postulated, but studies on this
      issue have yielded inconsistent results, partly due to limitations of
      investigative techniques. Many of these limitations can be overcome by the twitch
      interpolation technique, which is capable of accurately quantifying the degree of
      diaphragmatic activation, termed the voluntary drive to breathe. The hypothesis
      that patients with COPD and hypercapnia compensate for an acute increase in
      mechanical load on the inspiratory muscles with a lower voluntary drive to
      breathe than is the case with normocapnic patients was tested. Measurements were
      obtained in 15 patients with COPD, six of whom displayed hypercapnia and nine
      normocapnia. The maximum degree of diaphragmatic activation, expressed as a
      voluntary activation index (mean +/- SEM), was higher in hypercapnic than in
      normocapnic patients (98.7 +/- 0.7 versus 94.5 +/- 0.9% (p = 0.006)), as was the
      mean value (94.5 +/- 0.7 versus 88.5 +/- 1.9% (p = 0.01)). Within-patient values
      of the index were also less variable in the hypercapnic patients (coefficients of
      variation, 3.4 +/- 0.3 versus 6.1 +/- 0.9%, p = 0.01). Multiple regression
      analysis revealed the ratio of dynamic elastance to maximum transdiaphragmatic
      pressure, an index of inspiratory muscle loading, and pH as the only variables
      that correlated with maximum voluntary activation index (r2 = 0.69, p = 0.02 for
      each variable). Contrary to the hypothesis, it was concluded that voluntary
      activation of the diaphragm was greater and less variable in hypercapnic patients
      than normocapnic patients with severe chronic obstructive pulmonary disease
      during an acute increase in inspiratory mechanical load. Whether greater
      diaphragmatic recruitment during episodes of a severe exacerbation of chronic
      obstructive pulmonary disease provides a survival advantage for hypercapnic
      patients with chronic obstructive pulmonary disease remains to be determined.

PMID- 11510807
TI  - Ventilatory and cerebrovascular responses in normocapnic and hypercapnic COPD
      patients.
AB  - This study investigated the hypothesis that hypercapnia in some chronic
      obstructive pulmonary disease (COPD) patients may be related to a high
      cerebrovascular response to carbon dioxide (CO2). The relationship between
      responses of ventilation and of cerebral blood volume (CBV) to acute changes in
      carbon dioxide tension in arterial blood (Pa,CO2) was measured in 17 chronic
      hypercapnic (Pa,CO2 >6.0 kPa) and 16 normocapnic (Pa,CO2 < or = 6.0 kPa) COPD
      patients, who were matched for degree of airway obstruction (forced expiratory
      volume in one second 27% predicted). Results were compared with 15 age-matched
      healthy subjects. CBV was measured using near infrared spectroscopy during normo-
      and hypercapnia and related to inspired minute ventilation (V'I) and mouth
      occlusion pressure (P0.1). Hypercapnia (end-tidal pressure of carbon dioxide
      (deltaPET,CO2) > 1 kPa) was induced by giving adequate amounts of CO2 in the
      inspired air. During normocapnia, CBV (mL x 100 g(-1)) was 2.41+/- 0.66 and 2.90
      +/- 0.60 (mean +/- SD) in the normocapnic and chronic hypercapnic patients,
      respectively, which was significantly lower compared to healthy subjects (3.53 +/
      0.77). All slopes of CO2 responsiveness (deltaCBV/deltaPa,CO2,
      deltaV'I/deltaPa,CO2, deltaP0.1/deltaPa,CO2) were significantly lower in both
      COPD groups relative to healthy subjects, but were not significantly different
      between the COPD groups. A poor but positive correlation between ventilatory and
      cerebrovascular CO2 responsiveness (deltaCBV/deltaPa,CO2 and
      deltaV'I/deltaPa,CO2) was found in COPD patients and healthy subjects. The
      findings do not support the hypothesis of abnormal cerebrovascular responses to
      carbon dioxide in hypercapnic chronic obstructive pulmonary disease patients.

PMID- 11510808
TI  - Health-related quality of life in COPD: why both disease-specific and generic
      measures should be used.
AB  - Although research has consistently demonstrated that chronic obstructive
      pulmonary disease (COPD) impairs health-related quality of life (HRQL), little
      agreement has been evidenced regarding the factors identified as contributing to
      impaired HRQL. The aim was to study such factors using well established generic
      and specific HRQL instruments. The patients (n=68) were stratified by forced
      expiratory volume in one second (FEV1) to represent a wide range of disease
      severity. Pulmonary function, blood gases and 6-min walking distance test (6MWD)
      were assessed. HRQL instruments included: St George's Respiratory Questionnaire
      (SGRQ), Sickness Impact Profile (SIP), Hospital Anxiety and Depression Scale and
      Mood Adjective Check List. The strength of the impact of COPD on HRQL was
      represented along a continuum ranging from lung function, functional status
      (physical and psychosocial) to wellbeing. Although correlations between FEV1
      versus SGRQ total and SIP overall scores (r=-0.42 and -0.32) were stronger than
      previously reported, multiple regression analyses showed that lung function
      contributed little to the variance when dyspnoea-related limitation, depression
      scores and 6MWD were included in the models. These three factors were important
      to varying degrees along the whole range of HRQL. Physiological, functional and
      psychosocial consequences of chronic obstructive pulmonary disease are only
      poorly to moderately related to each other. The present study concludes that a
      comprehensive assessment of the effects of chronic obstructive pulmonary disease
      requires a battery of instruments that not only tap the disease-specific effects,
      but also the overall burden of the disease on everyday functioning and emotional
      wellbeing.

PMID- 11510809
TI  - Dose-response effect of oxygen on hyperinflation and exercise endurance in
      nonhypoxaemic COPD patients.
AB  - Dynamic hyperinflation contributes to exertional breathlessness and reduced
      exercise tolerance in chronic obstructive pulmonary disease (COPD) patients. This
      study examined whether oxygen supplementation results in a dose-dependent
      decrease in hyperinflation associated with functional and symptomatic
      improvement. Ten severe COPD patients without clinically significant oxygen (O2)
      desaturation during exercise, and seven healthy subjects, performed five exercise
      tests at 75% of maximally tolerated work rate. Inspired oxygen fraction (FI,O2)
      was varied (0.21, 0.3, 0.5, 0.75 and 1.0) among tests in a randomized order.
      Ventilation (V'E) was measured, and end-inspiratory (EILV) and end-expiratory
      (EELV) lung volume changes were assessed from inspiratory capacity manoeuvres. In
      the patients, compared to room air, endurance time increased with FI,O2=0.3
      (mean+/-SEM 92+/-20%) and increased further with FI,O2=0.5 (157+/-30%). At
      isotime, compared to room air, there were significant reductions in dyspnoea
      score, EELV, EILV, V'E and respiratory frequency (fR) with FI,O2=0.3. Improved
      endurance time negatively correlated with change in EELV (r=0.48, p=0.002) and
      EILV (r=0.43, p=0.005). The dyspnoea rating decrease correlated with fR decrease.
      In healthy subjects, smaller V'E and fR decreases were observed at FI,O2=0.5,
      accompanied by more modestly increased endurance. Oxygen supplementation during
      exercise induced dose-dependent improvement in endurance and symptom perception
      in nonhypoxaemic chronic obstructive pulmonary disease patients, which may be
      partly related to decreased hyperinflation and slower breathing pattern. This
      effect is maximized at an inspired oxygen fraction of 0.5.

PMID- 11510810
TI  - Variations in the prevalence across countries of chronic bronchitis and smoking
      habits in young adults.
AB  - The present work aims to assess the international variation in the prevalence of
      chronic bronchitis and its main risk factor, smoking habits, in young adults of
      35 centres from 16 countries. Respiratory symptoms and pulmonary function were
      assessed in 17,966 subjects (20-44 yrs), randomly selected from the general
      population, in the frame of the European Community Respiratory Health Survey. The
      median prevalence of chronic bronchitis was 2.6%, with wide variations across
      countries (p<0.001; 0.7-9.7%). The prevalence of current smokers ranged 20.1
      56.9%, (p<0.001) with a median value of 40%. Current smoking was the major risk
      factor for chronic bronchitis, especially in males. Its effect increased
      according to number of pack-yrs: in males, the odds ratio of chronic bronchitis
      was 3.51 (95% confidence interval (CI) 2.31-5.32) in 1-14 pack-yrs smokers and
      increased to 17.32 (9.97-30.11) in > or = 45 pack-yrs smokers with respect to
      nonsmokers. Only 30% of the geographical variability in prevalence could be
      explained by differences in smoking habits, suggesting that other environmental
      and/or genetic factors may play an important role. In conclusion, chronic
      bronchitis is a substantial health problem even in young adults. The impressive
      prevalence in current smokers in most countries highlights the need to improve
      the quality of prevention.

PMID- 11510811
TI  - Partial liquid ventilation improves lung function in ventilation-induced lung
      injury.
AB  - Disturbances in lung function and lung mechanics are present after ventilation
      with high peak inspiratory pressures (PIP) and low levels of positive end
      expiratory pressure (PEEP). Therefore, the authors investigated whether partial
      liquid ventilation can re-establish lung function after ventilation-induced lung
      injury. Adult rats were exposed to high PIP without PEEP for 20 min. Thereafter,
      the animals were randomly divided into five groups. The first group was killed
      immediately after randomization and used as an untreated control. The second
      group received only sham treatment and ventilation, and three groups received
      treatment with perfluorocarbon (10 mL x kg(-1), 20 mL x kg(-1), and 20 ml x kg(
      1) plus an additional 5 mL x kg(-1) after 1 h). The four groups were maintained
      on mechanical ventilation for a further 2-h observation period. Blood gases, lung
      mechanics, total protein concentration, minimal surface tension, and small/large
      surfactant aggregates ratio were determined. The results show that in ventilation
      induced lung injury, partial liquid ventilation with different amounts of
      perflubron improves gas exchange and pulmonary function, when compared to a group
      of animals treated with standard respiratory care. These effects have been
      observed despite the presence of a high intra-alveolar protein concentration,
      especially in those groups treated with 10 and 20 mL of perflubron. The data
      suggest that replacement of perfluorocarbon, lost over time, is crucial to
      maintain the constant effects of partial liquid ventilation.

PMID- 11510812
TI  - Evidence of block and randomly sequenced chondroitin polysaccharides: sequential
      enzymatic digestion and quantification using ion trap tandem mass spectrometry.
AB  - A method for determining the sequence type of the disaccharide repeat region of
      cartilage samples is introduced. The samples are sequentially subjected to
      selective and nonselective enzymatic digestion, and the isomeric products from
      each step are quantified using tandem mass spectrometry. The two-step
      digestion/quantification protocol identifies whether the global makeup of the
      polymer is "alternating", "random", or "blocked" with respect to the two main
      components of the cartilage, 4- and 6-sulfated disaccharides. Using this
      procedure, the sequence type of two biologically isolated chondroitin
      polysaccharides was identified. The results for chondroitin sulfate A, isolated
      from bovine trachea, are consistent with the 4- and 6-sulfated disaccharides
      randomly distributed throughout the repeat region of the polysaccharide. For
      chondroitin sulfate C, shark cartilage, the 6-sulfated disaccharides are adjacent
      to each other to a larger extent than one would expect for a randomly distributed
      polymer, indicating that "blocks" of repeating disaccharides with the same
      sulfation site are present.

PMID- 11510813
TI  - Molecular oxygen-sensitive fluorescent lipobeads for intracellular oxygen
      measurements in murine macrophages.
AB  - Intracellular oxygen concentration is of primary importance in determining
      numerous physiological and pathological processes in biological systems. This
      paper describes the development and application of micrometer-sized oxygen
      sensitive fluorescence lipobeads for intracellular measurements of molecular
      oxygen in J774 murine macrophages. A ruthenium diimine complex [Ru(bpy
      pyr)(bpy)2]C12 (bpy = 2,2'-bipyridine, bpy-pyr = 4-(1"-pyrenyl)-2,2'-bipyridine)
      is used as the oxygen indicator. The indicator exhibits high chemical and
      photostability and high sensitivity to oxygen. The indicator molecules are
      immobilized in a phospholipid membrane that coats polystyrene microparticles. The
      fluorescence of the lipobeads is effectively quenched by molecular oxygen. The
      fluorescence intensity of the oxygen-sensitive lipobeads is 3 times higher in a
      nitrogenated solution than in an oxygenated solution. The lipobeads are
      internalized by murine macrophages through phagocytosis. They maintain their
      spectral properties for 24 h in living cells when the cells are stored in
      phosphate-buffered saline at pH 7.4. The photostability, reversibility, and
      effect of hypoxia, hyperoxia, and oxidative stress on the intracellular level of
      oxygen in J774 murine macrophages are described.

PMID- 11510814
TI  - Determination of molecular self-diffusion coefficient  using multiple spin-echo
      NMR spectroscopy with removal of convection and background gradient artifacts.
AB  - A new approach is presented for the measurement of the self-diffusion
      coefficients of molecules in solution. It has been applied to metabolites in
      biofluids such as seminal and blood plasma at physiological temperature. The
      method is based on the double-gradient-spin-echo pulse sequence in which CPMG and
      bipolar gradient pulses have been implemented. The double-gradient spin-echo is
      shown to be useful in reducing the thermal convection that can cause over
      estimation of the diffusion coefficients. The multiple spin-echoes in association
      with the CPMG approach is also insensitive to background gradient artifacts. In
      addition, the CPMG sequence enables longer diffusion periods (up to seconds) to
      be used without phase distortion; therefore, the proposed method is suitable for
      determining the diffusion coefficients of small metabolites in biofluids, where
      the resonances of large molecules, such as proteins, are suppressed during the
      spin-echo period as a result of their fast relaxation.

PMID- 11510815
TI  - Quantification of ATOFMS data by multivariate methods.
AB  - Aerosol time-of-flight mass spectrometry (ATOFMS) is capable of measuring the
      sizes and chemical compositions of individual polydisperse aerosol particles in
      real time. A qualitative estimate of the particle composition is acquired in the
      form of a mass spectrum that must be subsequently interpreted in order to draw
      conclusions regarding atmospheric relevance. The actual problem involves
      developing a calibration that allows the mass spectral data to be transformed
      into estimates of the composition of the atmospheric aerosol. A properly
      calibrated ATOFMS system should be able to quantitatively determine atmospheric
      concentrations of various species. Ideally, it would be able to accomplish this
      more rapidly, accurately, with higher size and time resolution, and at a far
      lower marginal cost than the manual sampling methods that are currently employed.
      Attempts have already been made at using ATOFMS and similar techniques to extract
      the bulk chemical species concentration present in an ensemble of particles. This
      study represents the use of a multivariate calibration method, two-dimensional
      partial least-squares analysis, for calibrating single-particle mass spectral
      data. The method presented here is far less labor-intensive than the univariate
      methods attempted to date and allows for less observer bias. Because of the labor
      savings, this is also the most comprehensive calibration performed to date,
      resulting in the quantification of 44 different chemical species.

PMID- 11510816
TI  - Thermally assisted infrared multiphoton photodissociation in a quadrupole ion
      trap.
AB  - Thermally assisted infrared multiphoton photodissociation (TA-IRMPD) provides an
      effective means to dissociate ions in the quadrupole ion trap mass spectrometer
      (QITMS) without detrimentally affecting the performance of the instrument. IRMPD
      can offer advantages over collision-induced dissociation (CID). However,
      collisions with the QITMS bath gas at the standard pressure and ambient
      temperature cause IR-irradiated ions to lose energy faster than photons can be
      absorbed to induce dissociation. The low pressure required for IRMPD (< or = 10(
      5) Torr) is not that required for optimal performance of the QITMS (10(-3) Torr),
      and sensitivity and resolution suffer. TA-IRMPD is performed with the bath gas at
      an elevated temperature. The higher temperature of the bath gas results in less
      energy lost in collisions of the IR-excited ions with the bath gas. Thermal
      assistance allows IRMPD to be used at or near optimal pressures, which results in
      an approximately 1 order of magnitude increase in signal intensity. Unlike CID,
      IRMPD allows small product ions, those less than about one-third the m/z of the
      parent ion, to be observed. IRMPD should also be more easily paired with
      fluctuating ion sources, as the corresponding fluctuations in resonant
      frequencies do not affect IRMPD. Finally, while IR irradiation nonselectively
      causes dissociation of all ions, TA-IRMPD can be made selective by using axial
      expansion to move ions away from the path of the laser beam.

PMID- 11510817
TI  - Collision-induced dissociation of mobility-separated ions using an orifice
      skimmer cone at the back of a drift tube.
AB  - An ion mobility-mass spectrometry technique that incorporates a differentially
      pumped orifice-skimmer cone (OSC) region at the exit of the drift tube has been
      developed. The OSC region is similar in design to those used in electrospray
      ionization sources and offers improvements in ion transmission (by factors of
      approximately 5-10 compared with previous designs) and the ability to induce
      fragmentation of mobility-separated ions. The separation of ions prior to
      dissociation at the skimmer cone allows the origin of fragment ions to be
      examined. Here, we describe the experimental design and demonstrate the approach
      by examining fragment ions that are common to multiple charge states and
      different gas-phase ion conformations of electrosprayed angiotensin II and [Sar1,
      Val5, Ala8] angiotensin II peptides.

PMID- 11510819
TI  - Characterization of phosphoantigens by high-performance anion-exchange
      chromatography-electrospray ionization ion trap mass spectrometry and
      nanoelectrospray ionization ion trap mass spectrometry.
AB  - New phosphorylated microbial metabolites referred to as phosphoantigens activate
      immune responses in humans. Although these molecules have leading applications in
      medical research, no direct method allows their rapid and unambiguous structural
      identification. Here, we interfaced online HPAEC (high performance anion-exchange
      chromatography) with ESI-ITMS (electrospray ionization ion trap mass
      spectrometry) to identify such pyrophosphorylated molecules. A self-regenerating
      anion suppressor located upstream of electrospray ionization enabled the
      simultaneous detection of pyrophosphoester by conductimetry, UV and MS. By HPAEC
      ITMS and HPAEC-ITMS2, a single run permitted characterization of reference
      phosphoantigens and of related structures. Although all compounds were resolved
      by HPAEC, MS enabled their detection and identification by [M-H]- and fragment
      ions. Isobaric phosphoantigen analogues were also separated by HPAEC and
      distinguished by MS2. The relevance of this device was demonstrated for
      phosphoantigens analysis in human urine and plasma. Furthermore, identification
      of natural phosphoantigens by automatically generated 2D mass spectra from nano
      ESI-ITMS is presented. This last technique permits the simultaneous performance
      of molecular screening of natural phosphoantigen extracts and their
      identification.

PMID- 11510818
TI  - Identification and structural elucidation of lectin-binding oligosaccharides by
      bioaffinity matrix-assisted laser desorption/ionization Fourier transform mass
      spectrometry.
AB  - Cortical granule lectin (CGL) is released by the egg of the South African toad
      Xenopus laevis upon fertilization. The lectin binds to oligosaccharides in the
      extracellular matrix of the egg to form a physical block to prevent additional
      sperm penetration or polyspermy. To identify the oligosaccharides that bind to
      CGL, the lectin was immobilized on the surface of a matrix-assisted laser
      desorption/ionization probe. This bioaffinity probe was used to determine
      oligosaccharides that bind preferentially to CGL. Structural analyses based on
      collision-induced dissociation was used to determine that oligosaccharides with
      the sulfate esters at the nonreducing ends preferentially bind to the lectin.

PMID- 11510820
TI  - On-line high-precision stable hydrogen isotopic analyses on nanoliter water
      samples.
AB  - We describe a new on-line chromium reduction technique for the measurement of
      stable hydrogen (deltaD) isotopes in waters using continuous-flow isotope ratio
      mass spectrometry. The on-line Cr reduction method has low intersample memory
      effects (< 1%) and excellent precision and accuracy for deltaD (+/-0.5% and was
      used to analyze waters samples as small as 50 nL. The on-line Cr method has a
      number of significant advantages over conventional offline Zn and U reduction and
      on-line carbon-based pyrolysis techniques. A single Cr reactor can be used to
      analyze approximately 1,000 water samples using an injection volume of 0.5
      microL, with an individual sample analysis time of 4 min. Intersample memory
      effects are negligible. The Cr reactor temperature of 1050 degree C is easily
      attainable on standard elemental analyzers and so does not require the
      specialized and costly high-temperature furnaces of carbon-based pyrolysis
      reactors. Furthermore, hydrogen isotopes in extremely small water samples in the
      100-nL range or less can be easily measured; hence, this new method opens up a
      number of exciting application areas in earth and environmental sciences, for
      example, natural abundance deltaD measurements of individual fluid inclusions in
      geologic materials using a laser source and measurements of body fluids in
      physiological and metabolic research.

PMID- 11510821
TI  - Overalkylation of a protein digest with iodoacetamide.
AB  - Cystine linkages in proteins are often opened with reducing agents, sometimes to
      improve their digestion, often to eliminate disulfide linkages from complicating
      analysis of the digest. After reduction, the sulfhydryls are usually reacted with
      iodoacetamide (IAM), iodoacetic acid (IAA), or another electrophile to prevent
      reformation of disulfide linkages in a random manner. When the amount of protein
      may be reliably estimated, side reactions from excess IAM or IAA can be avoided.
      When this is not so, removal of excess iodoalkane can be accomplished by HPLC, by
      dialysis, or simply by allowing a reducing thiol to consume any excess. In mass
      spectrometric analysis of proteins isolated by 1D or 2D gels, removal of the
      excess iodoalkane is often accomplished simply by washing the gel prior to
      proteolytic digestion. During a recent study of the glutathionylation site
      mapping of actin, IAM was used to block any residual sulfhydryl groups remaining
      on the protein so that they would not displace glutathione from its initial site.
      In addition, to avoid losses due to actin polymerization during dialysis, the IAM
      was allowed to remain during the digestion. This further ensured that any
      sulfhydryl groups liberated during the digestion would be similarly blocked by
      the IAM. Under these conditions, we observed the peptides to undergo N- as well
      as S-carbamidomethylation. In examining a series of other peptides alkylated with
      IAM in this way, we have found N-alkylation to be the rule rather than the
      exception and even O-alkylation was detected. The main sites to which the
      carbamidomethyl group attaches to the peptides have been located with LC-MS2
      using an ion trap mass spectrometer and found to be the N-terminal amino group. A
      simple expedient to prevent such reactions when an excess of reducing agent must
      be avoided is to run the alkylation in the presence of a thioether such as 2,2'
      thiodiethanol rather than a thiol.

PMID- 11510822
TI  - Detection and partial structure elucidation of basic taxoids from Taxus
      wallichiana by electrospray ionization tandem mass spectrometry.
AB  - A sensitive method for the detection and characterization of basic taxoids from
      the ethyl acetate extract of Taxus wallichiana has been described. A combined
      analysis of the fragmentation spectra of 3 purified standard basic taxoids and
      the substructure analysis of 139 previously reported taxoids provided information
      on typical primary and secondary product ions that are generated by CID mass
      spectrometry of basic taxoids. Precursor-scan analysis of selected product ions
      allowed for the detection of 57 basic taxoids from the ethyl acetate extract of
      T. wallichiana, 45 of which have not been reported. The method describe in this
      paper provides a fast method for the "dereplication" of natural products. The
      mass spectrometric data derived by this method was sufficient for the partial
      structure elucidation of novel basic taxoids. The method presented in this paper
      can be easily adapted into a high-throughput screening protocol for the
      identification and characterization of bioactive natural products.

PMID- 11510823
TI  - A mobile mass spectrometer for comprehensive on-line analysis of trace and bulk
      components of complex gas mixtures: parallel application of the laser-based
      ionization methods VUV single-photon ionization, resonant multiphoton ionization,
      and laser-induced electron impact ionization.
AB  - A newly developed compact and mobile time-of-flight mass spectrometer (TOFMS) for
      on-line analysis and monitoring of complex gas mixtures is presented. The
      instrument is designed for a (quasi-)simultaneous application of three ionization
      techniques that exhibit different ionization selectivities. The highly selective
      resonance-enhanced multiphoton ionization (REMPI) technique, using 266-nm UV
      laser pulses, is applied for selective and fragmentationless ionization of
      aromatic compounds at trace levels (parts-per-billion volume range). Mass spectra
      obtained using this technique show the chemical signature solely of monocyclic
      (benzene, phenols, etc.) and polycyclic (naphthalene, phenathrene, indol, etc.)
      aromatic species. Furthermore, the less selective but still fragmentationless
      single photon ionization (SPI) technique with 118-nm VUV laser pulses allows the
      ionization of compounds with an ionization potential below 10.5 eV. Mass spectra
      obtained using this technique show the profile of most organic compounds
      (aliphatic and aromatic species, like nonane, acetaldehyde, or pyrrol) and some
      inorganic compounds (e.g., ammonia, nitrogen monoxide). Finally, the nonselective
      ionization technique laser-induced electron-impact ionization (LEI) is applied.
      However, the sensitivity of the LEI technique is adjusted to be fairly low. Thus,
      the LEI signal in the mass spectra gives information on the inorganic bulk
      constituents of the sample (i.e., compounds such as water, oxygen, nitrogen, and
      carbon dioxide). Because the three ionization methods (REMPI, SPI, LEI) exhibit
      largely different ionization selectivities, the isolated application of each
      method alone solely provides specific mass spectrometric information about the
      sample composition. Special techniques have been developed and applied which
      allow the quasi-parallel use of all three ionization techniques for on-line
      monitoring purposes. Thus, a comprehensive characterization of complex samples is
      feasible jointly using the characteristic advantages of the three ionization
      techniques. Laboratory applications show results on rapid overview
      characterization of mineral oil-based fuels and coffee headspace. The first
      reported field applications include timely resolved on-line monitoring results on
      automobile exhausts and of waste incineration flue gas.

PMID- 11510825
TI  - Automated tandem mass spectrometry by orthogonal acceleration TOF data
      acquisition and simultaneous magnet scanning for the characterization of
      petroleum mixtures.
AB  - The automated acquisition of the product ion spectra of all precursor ions in a
      selected mass range by using a magnetic sector/orthogonal acceleration time-of
      flight (oa-TOF) tandem mass spectrometer for the characterization of complex
      petroleum mixtures is reported. Product ion spectra are obtained by rapid oa-TOF
      data acquisition and simultaneous scanning of the magnet. An analog signal
      generator is used for the scanning of the magnet. Slow magnet scanning rates
      permit the accurate profiling of precursor ion peaks and the acquisition of
      product ion spectra for all isobaric ion species. The ability of the instrument
      to perform both high- and low-energy collisional activation experiments provides
      access to a large number of dissociation pathways useful for the characterization
      of precursor ions. Examples are given that illustrate the capability of the
      method for the characterization of representative petroleum mixtures. The
      structural information obtained by the automated MS/MS experiment is used in
      combination with high-resolution accurate mass measurement results to
      characterize unknown components in a polar extract of a refinery product. The
      exhaustive mapping of all precursor ions in representative naphtha and middle
      distillate fractions is presented. Sets of isobaric ion species are separated and
      their structures are identified by interpretation from first principles or by
      comparison with standard 70-eV EI libraries of spectra. The utility of the method
      increases with the complexity of the samples.

PMID- 11510824
TI  - High-sensitivity electron capture dissociation tandem FTICR mass spectrometry of
      microelectrosprayed peptides.
AB  - Electron capture dissociation (ECD) has previously been shown by other research
      groups to result in greater peptide sequence coverage than other ion dissociation
      techniques and to localize labile posttranslational modifications. Here, ECD has
      been achieved for 10-13-mer peptides microelectrosprayed from 10 nM (10
      fmol/microL) solutions and for tryptic peptides from a 50 nM unfractionated
      digest of a 28-kDa protein. Tandem Fourier transform ion cyclotron resonance
      (FTICR) mass spectra contain fragment ions corresponding to cleavages at all
      possible peptide backbone amine bonds, except on the N-terminal side of proline,
      for substance P and neurotensin. For luteinizing hormone-releasing hormone, all
      but two expected backbone amine bond cleavages are observed. The tandem FTICR
      mass spectra of the tryptic peptides contain fragment ions corresponding to
      cleavages at 6 of 12 (1545.7-Da peptide) and 8 of 21 (2944.5-Da peptide) expected
      backbone amine bonds. The present sensitivity is 200-2000 times higher than
      previously reported. These results show promise for ECD as a tool to produce
      sequence tags for identification of peptides in complex mixtures available only
      in limited amounts, as in proteomics.

PMID- 11510826
TI  - Purge-and-membrane mass spectrometry, a screening method for analysis of VOCs
      from soil samples.
AB  - Purge-and-membrane mass spectrometry (PAM-MS) is a combination of dynamic
      headspace sampling and membrane extraction. A new and simple purge-and-membrane
      sampler is introduced and its basic testing results for the analysis of VOCs in
      soil samples are reported. Soil moisture had no effect on desorption times in the
      case of sand, but the desorption times increased when the content of organic
      matter in the soil sample (garden soil) increased. The longest desorption times
      were measured with dry garden soil samples. For both types of samples, minor
      differences in desorption peak areas were observed between 10 and 20% moisture.
      Detection limits of the VOCs varied in the range 2-150 microg/kg, depending on
      the soil type. Good linearity (correlation coefficient > 0.990) was observed in
      the range 0.5-50 mg/kg. Aging of the spiked soil samples had only a slight effect
      on desorption peak areas for samples stored at 5 degrees C up to two weeks, but
      after six months of storing, differences were observed between dry sand and
      moistened garden soil. In both cases, peak areas were diminished. On average, 46%
      of compounds could be desorbed from the aged sand and 86% from the aged garden
      soil. The modified vapor fortification method was used in preparing standard soil
      samples, which were analyzed by static headspace gas chromatography (HSGC) and
      PAM-MS. Some authentic soil samples were also analyzed using both of these
      techniques. Many of the vapor fortification samples and the authentic samples
      were also analyzed in another laboratory by HSGC. The agreement between the
      methods and the laboratories was generally good.

PMID- 11510827
TI  - Trace determination of fluoroquinolone antibacterial agents in urban wastewater
      by solid-phase extraction and liquid chromatography with fluorescence detection.
AB  - Fluoroquinolones (FQs) are among the most important antibacterial agents
      (synthetic antibiotics) used in human and veterinary medicine. An analytical
      method based on reversed-phase liquid chromatography with fluorescence detection
      was developed and validated for the simultaneous determination of nine FQs and
      the quinolone pipemidic acid in urban wastewater. Aqueous samples were extracted
      using mixed-phase cation-exchange disk cartridges that were subsequently eluted
      by ammonia solution in methanol. Recoveries were above 80% at an overall
      precision of better than 10%. Instrumental quantification limits varied between
      150 and 450 pg injected. The presented method was successfully applied to
      quantify FQs in effluents of urban wastewater treatment plants. The two most
      abundant human-use FQs, ciprofloxacin and norfloxacin, occurred in primary and
      tertiary waste-water effluents at concentrations between 249 and 405 ng/L and
      from 45 to 120 ng/L, respectively. The identity of FQs in urban wastewater was
      confirmed by recording full fluorescence spectra and liquid chromatography
      directly coupled to tandem mass spectrometry. These results indicate that
      conventional environmental risk assessment overestimates FQ concentrations in
      surface waters by 1 to 2 orders of magnitude.

PMID- 11510828
TI  - Experimental factors controlling analyte ion generation in laser
      desorption/ionization mass spectrometry on porous silicon.
AB  - Desorption/ionization on porous silicon (DIOS) is a relatively new laser
      desorption/ionization technique for the direct mass spectrometric analysis of a
      wide variety of samples without the requirement of a matrix. Porous silicon
      substrates were fabricated using the recently developed nonelectrochemical H2O2
      metal-HF etching as a versatile platform for investigating the effects of
      morphology and physical properties of porous silicon on DIOS-MS performance. In
      addition, laser wavelength, mode of ion detection, pH, and solvent contributions
      to the desorption/ionization process were studied. Other porous substrates such
      as GaAs and GaN, with similar surface characteristics but differing in thermal
      and optical properties from porous silicon, allowed the roles of surface area,
      optical absorption, and thermal conductivities in the desorption/ionization
      process to be investigated. Among the porous semiconductors studied, only porous
      silicon has the combination of large surface area, optical absorption, and
      thermal conductivity required for efficient analyte ion generation under the
      conditions studied. In addition to these substrate-related factors, surface
      wetting, determined by the interaction of deposition solvent with the surface,
      and charge state of the peptide were found to be important in determining ion
      generation efficiency.

PMID- 11510829
TI  - Chiroselective self-directed octamerization of serine: implications for
      homochirogenesis.
AB  - Serine undergoes chiroselective self-directed oligomerization to form a singly
      protonated octamer under positive ion electrospray conditions, as identified by
      ion trap tandem mass spectrometry. The experiments also show a series of higher
      order clusters (metaclusters) corresponding to [(Ser8H)n]n+, n = 1, 2, 3. There
      is a magic number effect favoring formation of the protonated octamer over its
      homologues and also a strong preference for octamer formation from homochiral
      serine molecules. Collision-induced dissociation suggests that the protonated
      octamer is composed of four hydrogen-bonded dimers, stabilized by further
      extensive hydrogen bonding. Density functional calculations support this model
      and show that the protonated homochiral octamer is energetically stabilized
      relative to its possible fragments (dimer plus protonated hexamer, etc). The
      calculations also show that heterochiral octamers are less stable than homochiral
      octamers (e.g., the protonated 7:1 cluster is 2.1 kcal/mol less stable than the
      8:0 analogue). The implications of these results for the origin of homochirality
      are discussed.

PMID- 11510830
TI  - Laser modification of preformed polymer microchannels: application to reduce band
      broadening around turns subject to electrokinetic flow.
AB  - A pulsed UV excimer laser (KrF, 248 nm) was used to modify the surface charge on
      the side wall of hot-embossed microchannels fabricated in a poly(methyl
      methacrylate) substrate. Subablation level fluences, less than 2,385 mJ/cm2, were
      used to prevent any changes in the physical morphology of the surface. It is
      shown that the electroosmotic mobility, induced by an electric field applied
      along the length of the channel, increases by an average of 4% in the regions
      that have been exposed to UV laser pulses compared to nonexposed regions.
      Furthermore, application of UV modification to electroosmotic flow around a 90
      degrees turn results in a decrease in band broadening, as measured by the average
      decrease in the plate height of 40% compared to flow around a nonmodified turn.
      The ability to modify the surface charge on specific surfaces within a preformed
      plastic microchannel allows for fine control, adjustment, and modulation of the
      electroosmotic flow without using wall coatings or changing the geometry of the
      channel to achieve the desired flow profile.

PMID- 11510831
TI  - Chemical plume tracking. 1. Chemical information encoding.
AB  - It is shown experimentally that chemical information can be encoded and preserved
      in flowing liquid streams. It can be retrieved by chemical sensing arrays using
      correlation analysis. This finding is important for understanding of the
      mechanism of chemotaxis as practiced by some aquatic animals and also is a
      necessary prerequisite for construction of chemical plume tracking robots.

PMID- 11510832
TI  - Chemical plume tracking. 2. Multiple-frequency modulation.
AB  - The purpose of this research is to estimate the effect of turbulent mixing on the
      information content in a chemically encoded signal, to investigate the effect of
      the presence of multiple encoded frequencies, and to evaluate the information
      contained in the higher harmonics of the coherence spectra. The virtual plume
      instrument is used to mimic the flow conditions and signal patterns in a real
      chemical plume. Two-frequency modulation experiments are performed using solenoid
      valves to introduce concentration plugs of a marker into the carrier flows at
      certain constant frequencies. In our experiments, the length of the delay
      elements and the dispersion were varied to mimic different characteristics of the
      turbulent plume. In addition, an artificial but uncorrelated white noise was
      added to the raw amperometric signals in order to simulate the "noisy" conditions
      existing in a real plume. Our experiments reveal that the introduced turbulence
      has only a marginal effect on the coherence spectra. Moreover, it is shown that
      when the second frequency is present in the plume, both fundamental frequencies
      can be unambiguously assigned. Higher harmonics in the coherence spectra have
      been found to depend on the distance from the source. These findings are
      important for understanding of the mechanism of chemotaxis and may also lead to
      the design of optimized search algorithms for chemical plume tracking robots.

PMID- 11510833
TI  - Single-molecule detection using surface-enhanced resonance Raman scattering and
      Langmuir-Blodgett monolayers.
AB  - The Langmuir-Blodgett (LB) technique has been used to obtain spatially resolved
      surface-enhanced resonance Raman scattering (SERRS) spectra of single dye
      molecules dispersed in the matrix of a fatty acid. The experimental results
      presented here mimic the original electrochemical surface-enhanced Raman
      scattering (SERS) work where the background bulk water did not interfere with the
      detection of the SERS signal of molecules adsorbed onto the rough silver
      electrode. LB monolayers of the dye in fatty acid have been fabricated on silver
      island films with a concentration, in average, of one probe molecule per
      micrometer square. The properties of single-molecule spectroscopy were
      investigated using micro-Raman including mapping and global images. Blinking of
      the SERRS signal was also observed.

PMID- 11510834
TI  - Ionic liquids as matrixes for matrix-assisted laser desorption/ionization mass
      spectrometry.
AB  - Room-temperature ionic liquids are useful as solvents for organic synthesis,
      electrochemical studies, and separations. We wished to examine whether their high
      solubalizing power, negligible vapor pressure, and broad liquid temperature range
      are advantageous if they are used as matrixes for UV-MALDI. Several different
      ionic matrixes were synthesized and tested, using peptides, proteins, and
      poly(ethylene glycol) (PEG-2000). All ionic liquids tested have excellent
      solubilizing properties and vacuum stability compared to other commonly used
      liquid and solid matrixes. However, they varied widely in their ability to
      produce analyte gas-phase ions. Certain ionic matrixes, however, produce
      homogeneous solutions of greater vacuum stability, higher ion peak intensity, and
      equivalent or lower detection limits than currently used solid matrixes. Clearly,
      ionic liquids and their more amorphous solid analogues merit further
      investigation as MALDI matrixes.

PMID- 11510835
TI  - Electrophoresis in nanometer inner diameter capillaries with electrochemical
      detection.
AB  - Separations have been achieved in 770- and 430-nm-inner diameter capillaries. The
      extremely low sample volumes involved in the study of biological
      microenvironments such as single cells has led to the desire to develop
      separation techniques in these ultrasmall capillaries. Total sample volumes as
      low as 12 fL have been injected using these nanometer inner diameter capillaries.
      Separations of several catecholamines have been accomplished in these
      submicrometer capillaries using both capillary zone electrophoresis and micellar
      electrokinetic chromatography with end-column amperometric detection.

PMID- 11510836
TI  - Characterization of asphalt fume composition under simulated road paving
      conditions by GC/MS and microflow LC/quadrupole time-of-flight MS.
AB  - A highly sensitive, selective, and reliable analytical method has been developed
      and validated for characterization of asphalt fume generated under simulated road
      paving conditions. A dynamic asphalt fume generation system was modified to
      provide consistent test atmospheres at simulated asphalt road paving conditions.
      In the process of fume generation, asphalt was initially preheated in an oven to
      170 degrees C, pumped to a large kettle, which maintained the asphalt temperature
      between 150 and 170 degrees C, and then transferred to the generator. The fume
      was conducted from the generator to an exposure chamber through a heated transfer
      line. Characterization of the asphalt fume test atmospheres included the
      following: (1) determination of the consistency of the asphalt aerosol
      composition within the generation system; (2) quantification of total organic
      matter of the asphalt fume by electron impact ionization of isotope dilution gas
      chromatography/ mass spectrometry); and (3) identification of individual priority
      polycyclic aromatic hydrocarbons (PAHs) in asphalt fume by selected ion
      monitoring. With the developed method, asphalt fumes could be characterized into
      three fractions: (1) filter collection of a large molecular size fraction over a
      range of mass-to-charge (m/z) ratios of 173-309; (2) XAD-2 trapping of a medium
      molecular size fraction over a range of m/z ratios of 121-197; and (3) charcoal
      trapping of a small molecular size fraction that contained mainly the volatile
      vapor fraction over a range of m/z ratios of 57-141. Total organic matter of the
      asphalt fume was quantified over the 5 exposure days. Sixteen specific priority
      PAHs were monitored and identified. These PAHs were determined at trace levels on
      the filter fraction. A novel approach, which utilizes collision-induced
      dissociation of fragmentation pathway leading to a characteristic fragmentation
      pattern by coupling microflow liquid chromatography to atmospheric pressure
      chemical ionization of quadrupole time-of-flight mass spectrometry, was used to
      further clarify the trace amount of key components present in simulated road
      paving asphalt fumes. These results demonstrate that asphalt fume composition
      could be characterized and specific priority PAHs could be identified by this
      method. The major advantages of this method are its highly sensitivity,
      selectivity, and reliability for chemical hazard characterization in a complex
      mixture. This method is suitable for support toxicity studies using simulated
      occupational exposure to asphalt fumes.

PMID- 11510837
TI  - Perfluorosulfonated ionomer-modified polyethylene. A material for simultaneous
      solid-phase enrichment and enhanced precolumn dansylation of C-21 ketosteroids in
      human serum.
AB  - A new derivatization procedure has been developed where solid-phase catalysis is
      utilized to facilitate the formation of hydrazones in precolumn labeling of keto
      containing compounds. This procedure has been implemented on a solid-phase
      enrichment and enhanced derivatization (SPEED) device, prepared from porous
      polyethylene that has been coated with Nafion and dansylhydrazine. The SPEED
      devices have been optimized using experimental design and characterized for
      dansylation of C-21 ketosteroids by multivariate data analysis, using
      progesterone as the model compound. The reaction temperature and the molar ratio
      between the steroid and the derivatization reagent were found to be the factors
      most strongly affecting the reaction. Faster reaction kinetics were achieved when
      the molar ratio between dansylhydrazine and the steroid was increased. Mass
      spectroscopic analysis showed that the four derivative peaks eluting when
      derivatized progesterone was separated on an octadecyl silica stationary phase
      were due to the syn and anti mono- and bis(hydrazones) formed in the reaction.
      Using optimal reaction conditions, the derivatives mainly constitute the syn and
      anti conformers of bis-derivatives. In contrast to solution-based acid catalysis,
      the SPEED device was remarkably insensitive to water in the reaction mixture. A
      sample volume of 400 microL was found to be the maximum, enabling sample
      enrichment prior derivatization. Using optimal experimental conditions, picomole
      amounts of ketosteroids could be derivatized in 10 min at room temperature.
      Analysis of spiked serum samples containing 0.4-2.0 nmol of progesterone showed
      overall recoveries of 52-63%. The corresponding 3delta detection limit was 1.3
      pmol (n = 4, 100 microL injected), as estimated from calibration curve data.

PMID- 11510838
TI  - Sulfur species in volcanic gases.
AB  - A new analytical method for the determination of the sulfur species (SO2, H2S,
      S8(0)) in volcanic gases is proposed by revising, updating, and improving
      previous methods. The most significant advantages of the proposed procedure can
      briefly be summarized, as follows: (i) the reaction among sulfur species stops
      during the gas sampling by using preevacuated thorion-tapped vials with purified
      0.15M Cd(OH)2 in 4 M NaOH to favor the precipitation of H2S as CdS; (ii) all the
      sulfur species (SO2, H2S, S8(0)) are analyzed by ion chromatography, after
      conversion to SO4, which allows the detection limit to be lowered significantly
      with respect to the previous studies; (iii) appropriate aliquots from
      intermediate steps may be used to determine other species commonly present in
      volcanic gases such as CO2, HCI, HF, HBr, HI, and so forth; (iv) determination of
      all the other gas species is not jeopardized by the proposed method, i.e., one
      single vial can be used for analyzing the full chemical composition of a volcanic
      gas with the exception of NH3. Statistical parameters calculated from gas
      sampling data at the F5 crater fumarole in Vulcano Island (Aeolian Islands,
      southern Italy), suggest that the standard error of mean (s/ root n) is higher
      for S (0.10), followed by SO2, H2S, and CO2 (0.04, 0.038, and 0.028,
      respectively). SO2 shows the higher variation coefficient (12.1%) followed by
      H2S, S, and CO2 (5.7, 1.5, and 0.8%, respectively). Furthermore, if the time
      dependence of sampling is taken into account, the measured values, instead of
      fluctuating in a random manner, tend to follow systematic patterns, out of
      statistical control, possibly suggesting a sort of natural fluctuation of the
      volcanic system. Other crater fumaroles from volcanic systems located in
      different geodynamical areas (Hawaii, USA, El Chichon, Mexico, Poas, Costa Rica)
      have been analyzed as well.

PMID- 11510840
TI  - Description of the analysis of a wide range of volatile organic compounds in
      whole air samples collected during PEM-tropics A and B.
AB  - A large number of hydrocarbons, halocarbons, and organic nitrates were quantified
      in whole air samples acquired for the NASA-sponsored GTE missions PEM-Tropics A
      and B. The samples were collected in electro-polished stainless steel canisters
      from two aircraft while flying over the Pacific Basin. Two nominally identical
      multicolumn multidetector gas chromatographic analytical systems were employed.
      Whole air samples were also used as working and calibrated standards and were
      collected specifically for this purpose. This paper describes the analytical
      procedure employed during PEM-Tropics B. Minor differences in the PEM-Tropics A
      system will also be discussed. More than 3,900 samples were analyzed for 34 gases
      during PEM-Tropics A, over 4,500 samples were analyzed for 58 gases during PEM
      Tropics B. An overview is presented of the collection, analysis, and
      quantification of whole air samples during the PEM-Tropics missions, along with
      an analysis of the analytical precision achieved during these missions.

PMID- 11510839
TI  - High-throughput liquid chromatography/mass spectrometry method for the
      determination of the chromatographic hydrophobicity index.
AB  - A fast gradient reversed-phase liquid chromatography (LC) method, using an
      acetonitrile gradient was developed to determine the chromatographic
      hydrophobicity index (CHI), as reported by Valco et al. (Anal. Chem. 1997, 69,
      2022-2029). The analytical method provides retention times, based on UV detection
      at two different wavelengths, which then are converted into CHI values after
      calibration with a set of test compounds. The CHI of each compound is measured at
      three different pH values, 2.0, 7.4, and 10.5; so using an 8-min gradient at each
      pH value one compound can be analyzed in approximately 24 min. The aim of this
      work is to improve the throughput of the CHI screening using a LC/MS approach, so
      the application of the LC/MS technique is an extension of the LC/UV approach
      previously reported by Valco et al. This approach allows contemporary injection
      of N compounds into the LC/MS system, the retention time of each compound can be
      then extracted from the selected ion recording chromatograms. The throughput of
      the existing screening method could be increased by N times, where N is the
      number of compounds injected, so only three runs are needed to determine the CHI
      at three different pH values for a set of N compounds. The highest value of N
      depends on the total number of channels that can be monitored simultaneously; in
      the present work, 32 channels were used. This LC/MS method has been tested for a
      number of commercial products analyzed as mixtures, and data obtained were
      compared with those coming from the classical LC/UV approach. In the same way,
      the method was tested for a number of compounds associated with two GlaxoWellcome
      projects in the antibacterial area. Data reported show that the LC/MS method can
      be successfully applied for analyzing compounds in mixtures and for compounds
      with poor UW absorption, which cannot be analyzed with the standard LC/UV method.

PMID- 11510841
TI  - Ultrasonic extraction followed by sonolysis-ozonolysis as a sample pretreatment
      method for determination of reactive arsenic toward sodium tetrahydroborate by
      flow injection-hydride generation AAS.
AB  - A new sample pretreatment method based on ultrasonic extraction in HCI medium and
      subsequent oxidation of the extracts by sonozone (i.e., sonolysis-ozonolysis) has
      been developed for determination of reactive arsenic toward sodium
      tetrahydroborate [mainly As(III) + As(V)] by flow injection-hydride generation
      atomic absorption spectrometry. This method avoids the use of intensive
      treatments with concentrated and corrosive acids, high pressures, and
      temperatures that are inherent with traditional wet or dry ashing procedures and
      entails reduced waste production and reagent consumption. A sonozone process at
      room temperature was optimized to break the bond of As to proteins and
      macromolecular constituents which was an essential requirement for effective
      reduction by L-cysteine prior to arsine generation. Spiking experiments showed
      that As(III), As(V), MMA, and DMA were fully recovered from several matrixes on
      applying the above treatment. On the other hand, a nonreducible As species such
      as arsenobetaine that is predominant in some biological samples remained
      unchanged. Application of the method to sediment, soil, fly ash, and plant CRMs
      demonstrated that, in general, a good agreement existed between certified and
      found As contents, thereby indicating the absence of nonreducible As forms. Low
      As recoveries were observed for fish CRMs, as a result of the nondegradability of
      arsenobetaine by sonozone. The detection limit of As in the samples investigated
      was in the range 0.19-2.8 microg g(-1).

PMID- 11510842
TI  - Influence of structural variation in room-temperature ionic liquids on the
      selectivity and efficiency of competitive alkali metal salt extraction by a crown
      ether.
AB  - An improved method for the preparation of 1-alkyl-3-methylimidazolium
      hexafluorophosphates provides a series of room-temperature ionic liquids (RTILs)
      in which the 1-alkyl group is varied systematically from butyl to nonyl. For
      competitive solvent extraction of aqueous solutions of alkali metal chlorides
      with solutions of dicyclohexano-18-crown-6 (DC18C6) in these RTILs, the
      extraction efficiency generally diminished as the length of the 1-alkyl group was
      increased. Under the same conditions, extraction of alkali metal chlorides into
      solutions of DC18C6 in chloroform, nitrobenzene, and 1-octanol was undetectable.
      The extraction selectivity order for DC18C6 in the RTILs was K+ > Rb+ > Cs+ > Na+
      > Li+. As the alkyl group in the RTIL was elongated, the K+/ Rb+ and K+/Cs+
      selectivities exhibited general increases with the larger enhancement for the
      latter. For DC18C6 in 1-octyl-3-methylimidazolium hexafluorophosphate, the alkali
      metal cation extraction selectivity and efficiency were unaffected by variation
      of the aqueous-phase anion from chloride to nitrate to sulfate.

PMID- 11510843
TI  - Inverse 18O labeling mass spectrometry for the rapid identification of
      marker/target proteins.
AB  - Systematic analysis of proteins is essential in understanding human diseases and
      their clinical treatments. To achieve the rapid and unambiguous identification of
      marker or target proteins, a new procedure termed "inverse labeling" is proposed.
      With this procedure, to evaluate protein expression of a diseased or a drug
      treated sample in comparison with a control sample, two converse labeling
      experiments are performed in parallel. The perturbed sample (by disease or by
      drug treatment) is labeled in one experiment, whereas the control is labeled in
      the second experiment. When mixed and analyzed with its unlabeled counterpart for
      differential comparison using mass spectrometry, a characteristic inverse
      labeling pattern of mass shift will be observed between the two parallel analyses
      for proteins that are differentially expressed. In this study, protein labeling
      is achieved through 18O incorporation into peptides by proteolysis performed in
      [18O]water. Once the peptides are identified with the characteristic inverse
      labeling pattern of 18O/16O ion intensity shift, MS data of peptide fingerprints
      or peptide sequence information can be used to search a protein database for
      protein identification. The methodology has been applied successfully to two
      model systems in this study. It permits quick focus on the signals of
      differentially expressed proteins. It eliminates the detection ambiguities caused
      by the dynamic range of detection on proteins of extreme changes in expression.
      It enables the detection of protein modifications responding to perturbation.
      This strategy can also be extended to other protein-labeling methods, such as
      chemical or metabolic labeling, to realize the same benefits.

PMID- 11510844
TI  - Oxygen consumption of single bovine embryos probed by scanning electrochemical
      microscopy.
AB  - Oxygen consumption of individual bovine embryos was noninvasively quantified by
      scanning electrochemical microscopy (SECM). A probe microelectrode was used to
      scan near a single embryo surface in a culture medium to monitor the oxygen
      reduction current at 37 degrees C, under a water-saturated atmosphere of 5% CO2
      and 95% air. The oxygen concentration profiles near the embryos were in good
      agreement with the theoretical spherical diffusion. When an embryo reached the
      stage of a morula with a 74-microm radius on day 6 after in vitro fertilization,
      the oxygen concentration difference (deltaC) between the bulk solution and the
      morula surface was 6.90 +/- 1.35 microM. The oxygen consumption rate (F) of the
      single morula was estimated to be (1.40 +/- 0.27) x 10(-14) mol s(-1). After the
      SECM measurement, the embryo was continuously cultured for another 2 days and
      grew to the stage of a blastocyst with a 100-microm radius. For the blastocyst,
      the deltaC values for the inner cell mass side and the trophoblast side were
      16.40 +/- 1.83 and 9.14 +/- 1.68 microM, respectively. The oxygen consumption
      rate of the blastocyst was found to be in the range of (2.50 +/- 0.46) x 10(-14)
      mol s(-1) < F < (4.49 +/- 0.50) x 10(-14) mol s(-1). We have carried out SECM
      measurements for 19 embryos, and the results were compared in detail with these
      from an optical microscopic observation. The deltaC values for the morulae on day
      6 after in vitro fertilization were strongly related to the morphological embryo
      quality. The morulae showing a larger deltaC value developed into blastocysts of
      a larger size, and the deltaC value after the subsequent 2 days of cultivation
      was found to be increased.

PMID- 11510845
TI  - Development and application of a self-referencing glucose microsensor for the
      measurement of glucose consumption by pancreatic beta-cells.
AB  - Glucose gradients generated by an artificial source and beta-cells were measured
      using an enzyme-based glucose microsensor, 8-microm tip diameter, as a self
      referencing electrode. The technique is based on a difference measurement between
      two locations in a gradient and thus allows us to obtain real-time flux values
      with minimal impact of sensor drift or noise. Flux values were derived by
      incorporation of the measured differential current into Fick's first equation. In
      an artificial glucose gradient, a flux detection limit of 8.2 +/- 0.4 pmol.cm(
      2).s(-1) (mean +/- SEM, n = 7) with a sensor sensitivity of 7.0 +/- 0.4 pA/ mM
      (mean +/- SEM, n = 16) was demonstrated. Under biological conditions, the glucose
      sensor showed no oxygen dependence with 5 mM glucose in the bulk medium. The
      addition of catalase to the bulk medium was shown to ameliorate surface-dependent
      flux distortion close to specimens, suggesting an underlying local accumulation
      of hydrogen peroxide. Glucose flux from beta-cell clusters, measured in the
      presence of 5 mM glucose, was 61.7 +/- 9.5 fmol.nL(-1).s(-1) (mean +/- SEM, n =
      9) and could be pharmacologically modulated. Glucose consumption in response to
      FCCP (1 microM) transiently increased, subsequently decreasing to below basal by
      93 +/- 16 and 56 +/- 6%, respectively (mean +/- SEM, n = 5). Consumption was
      decreased after the application of 10 microM rotenone by 74 +/- 5% (mean +/- SEM,
      n = 4). These results demonstrate that an enzyme-based amperometric microsensor
      can be applied in the self-referencing mode. Further, in obtaining glucose flux
      measurements from small clusters of cells, these are the first recordings of the
      real-time dynamic of glucose movements in a biological microenvironment.

PMID- 11510846
TI  - Improved detection limits and sensitivities of potentiometric titrations.
AB  - Zero-current ion fluxes through polymer membranes of ion-selective electrodes
      (ISEs) may lead to biased endpoints of potentiometric titrations. The bias is
      eliminated, and the sensitivity of the end-point detection is improved through
      reducing transmembrane ion fluxes by an appropriate choice of the inner solution.
      Surprisingly, ISE membranes that have a significant primary ion flux toward the
      inner solution show much larger sensitivities than expected by titration theory;
      however, depending on the experimental conditions, their application may bias the
      endpoint. With the optimal systems, endpoint detection is now possible with total
      sample concentrations below 10(-6) M, as demonstrated by the titration of EDTA
      with a Pb2+ solution.

PMID- 11510847
TI  - Fluidics cube for biosensor miniaturization.
AB  - To create a small, portable, fully automated biosensor, a compact means of fluid
      handling is required. We designed, manufactured, and tested a "fluidics cube" for
      such a purpose. This cube, made of thermoplastic, contains reservoirs and
      channels for liquid samples and reagents and operates without the use of any
      internal valves or meters; it is a passive fluid circuit that relies on pressure
      relief vents to control fluid movement. We demonstrate the ability of pressure
      relief vents to control fluid movement and show how to simply manufacture or
      modify the cube. Combined with the planar array biosensor developed at the Naval
      Research Laboratory, it brings us one step closer to realizing our goal of a
      handheld biosensor capable of analyzing multiple samples for multiple analytes.

PMID- 11510848
TI  - Fractionation of moderate molecular weight polysiloxanes by centrifugal TLC.
AB  - Fractionation of polydispersed polysiloxanes (1-2 g) into narrow molecular weight
      fractions has been achieved by a rapid (30-60 min) convenient process, using the
      Cyclograph Centrifugal Chromatography System. These narrow molecular weight
      poly(dimethylsiloxane) fractions can be used as secondary standards for GPC.

PMID- 11510849
TI  - Continuous spore disruption using radially focused, high-frequency ultrasound.
AB  - We report on the development of a novel, continuous-flow, radially focused
      ultrasonic disruptor capable of lysing Bacillus spores in the absence of added
      chemical denaturants, enzymes, or microparticles. Greater than 99% disruption was
      achieved for Bacillus globigii spores and Escherichia coli and Bacillus subtilis
      vegetative cells with sample residence times of 62, 12, and 12 s, respectively.
      Microscopic and SEM images indicated that at equivalent power levels, the
      incidence of cell death or loss of viability typically exceeded the efficiency of
      (visible) cell lysis. However, semiquantitative PCR showed up to a 1,000-fold
      increase in intracellular DNA availability from ultrasonically disrupted spores,
      and liberated DNA was intact and available for subsequent detection.

PMID- 11510850
TI  - Microwave-assisted extraction of polycyclic aromatic hydrocarbons from marine
      sediments using nonionic surfactant solutions.
AB  - Microwave-assisted micellar extraction (MAME) has been tested for the recovery of
      polycyclic aromatic hydrocarbons (PAHs) present in samples of marine sediments.
      An aqueous solution of the nonionic surfactant polyoxyethylene(23)dodecyl ether
      (Brij 35) was employed as the extracting medium. The proposed approach showed
      recovery efficiencies comparable to those afforded by the Soxhlet technique with
      organic solvents, but a neat reduction of the extraction times and a better
      reproducibility were observed. A MAME-based protocol was successfully applied for
      the analysis of a certified sample.

PMID- 11510851
TI  - Sensing DNA in a flash.

PMID- 11510852
TI  - Using NSOM to study surfaces.

PMID- 11510853
TI  - Multicolor nanoparticle labels for DNA arrays.

PMID- 11510854
TI  - Sizing up diesel engine nanoparticles.

PMID- 11510855
TI  - Characterizing metal-molecule-metal junctions.

PMID- 11510856
TI  - Detection in the danger zone.

PMID- 11510857
TI  - LED source becomes a sensor.

PMID- 11510859
TI  - Heartfelt capillary LC/dual microelectrode system.

PMID- 11510858
TI  - Octamer clusters break the symmetry barrier.

PMID- 11510860
TI  - Black dust--better than gold.

PMID- 11510861
TI  - Environmental tool chest.

PMID- 11510862
TI  - Monolithic LC columns.

PMID- 11510863
TI  - Systematic LC/MS metabolite identification in drug discovery.

PMID- 11510864
TI  - Remote experimentation over the Net: our first year with MALDI.

PMID- 11510865
TI  - Finding the right robot for MALDI.

PMID- 11510866
TI  - Evidence that the branched-chain amino acid L-valine prevents exercise-induced
      release of 5-HT in rat hippocampus.
AB  - The branched-chain amino acid L-valine competes with tryptophan for transport
      into the brain and has previously been shown to decrease brain 5-HT synthesis.
      The purpose of this study was to assess, using a combined venous catheterization
      and in vivo microdialysis method, the effect of pre-exercise L-valine
      administration on 5-hydroxytryptamine (5-HT) metabolism in the ventral
      hippocampus of rats submitted to an acute intensive treadmill running (120 min at
      25 m x min(-1) followed by 150 min of recovery). The presented results include
      measurement of extracellular tryptophan (TRP), the 5-HT precursor, and
      extracellular 5-hydroxyindoleacetic acid (5-HIAA), the 5-HT metabolite. The data
      clearly demonstrate that exercise induces 5-HT release in the rat hippocampus: in
      control group, hippocampal 5-HT levels increase from 123.7 +/- 6.4% at the end of
      exercise to 133.9 +/- 6.4% after 60 min of recovery. Moreover, two hours of
      intensive running induced significant increases both in extracellular TRP levels
      (from 120 min of exercise to 30 min of recovery) and 5-HIAA levels (from 90 min
      of exercise to 90 min of recovery). Pre-exercise administration of L-valine
      prevents significantly the exercise-induced 5-HT release: 5-HT levels are
      maintained to baseline during exercise and recovery. With regard to the
      competitive effect of L-valine with TRP, we could observe a treatment-induced
      decrease in brain TRP levels (from 120 min of exercise to the end of recovery).
      Besides, L-valine does not prevent exercise-induced increase in 5-HIAA levels.
      The present study evidences that an acute intensive exercise stimulates 5-HT
      metabolism in the rat hippocampus, and that a pre-exercise administration of L
      valine prevents, via a limiting effect on 5-HT synthesis, exercise-induced 5-HT
      release. This study provides some anwers to previous human and animal
      investigations, showing physiological and psychological benefits of branched
      chain amino acids supplementation on performance.

PMID- 11510867
TI  - Decoupling of intracellular calcium signaling in granulocytes after exhaustive
      exercise.
AB  - There is growing evidence that exhaustive exercise can induce a suppression of
      the innate immune functions. Most studies so far describe exercise induced
      changes in cell counts or functional responses while information regarding
      intracellular signal transduction parameters is lacking. Therefore in the present
      study we investigated in granulocytes the regulation of intracellular calcium
      ([Ca2+]i) which is an important intracellular second messenger. Healthy
      volunteers underwent a treadmill exercise test at 80% of their maximal oxygen
      uptake until exhaustion. Granulocytes were separated before and 1 hour after the
      test. [Ca2+]i was analyzed spectrophotometrically using the Ca2+ sensitive
      fluorescent dye Fura-2, while the oxidative burst and phagocytosis were measured
      by flow cytometry. While resting [Ca2+]i levels were unchanged, the Ca2+
      transient induced N-formyl-methionyl-leucyl phenylalanine (fMLP) and platelet
      activating factor (PAF) were enhanced 1 hour after the test compared to pre
      exercise values although fMLP receptor density did not change. In contrast,
      oxidative burst and phagocytosis evoked by fMLP and phorbol-myristate-acetate
      (PMA) were decreased after exercise. Together, our data support the view that
      exhaustive exercise affects regulation of Ca2+ signaling in granulocytes. The
      potentiation of Ca2+ signals is not accompanied by an enhancement of cellular
      functional parameters suggesting a blockade in intracellular signalling pathways.

PMID- 11510868
TI  - Exercise performance is not influenced by a 5-HT reuptake inhibitor.
AB  - The purpose of the present study was to examine the effect of a selective
      serotonin (5-HT) reuptake inhibitor (SSRI) on exercise performance during a 90
      min time trial. Eight well trained male cyclists (VO2max 68.1 +/- 9.5 ml/kg/min)
      performed three 90 min time trials at 65% Wattmax. Blood samples were collected
      via an indwelling venous catheter for adrenocorticotropin hormone (ACTH),
      prolactin (PRL), cortisol, catecholamines, growth hormone (GH) and beta
      endorphins. The evening before and the morning of the time trials, the subjects
      ingested a capsule containing either placebo (lactose) or 20 mg Fluoxetine-HCI
      (Prozac, Ely Lilly Belgium). A double blind, randomized, placebo controlled,
      cross-over design was performed. Performance was not influenced by the SSRI. As
      expected, all blood parameters increased significantly during exercise (p <
      0.05). During the SSRI trial most parameters were slightly lower but only
      significantly for endorphins and PRL (p < 0.05). The results demonstrate that
      performance is not influenced by an SSRI, although some plasma hormones indicate
      a central effect of the drug. Surprisingly, the increases in PRL and endorphins
      were lower during the SSRI trial, meaning that the hormonal modulation during
      exercise might be regulated by the interaction between neurotransmitters rather
      than by serotonin alone.

PMID- 11510869
TI  - Platelet activation through triathlon competition in ultra-endurance trained
      athletes: impact of thrombin and plasmin generation and catecholamine release.
AB  - The aims of this study were to evaluate whether platelets are activated during
      strenuous exercise in healthy athletes. Also, to determine the impact of plasmin
      and thrombin activity and catecholamine release. Previous studies have shown
      activation of the hemostatic system after competitive exercise, but platelet
      activation was thought to be absent in trained athletes. The impact of thrombin
      and other potent platelet activators is still a matter for debate. We examined 30
      healthy triathletes during a triathlon competition. Flow cytometric detection of
      CD62p (P-selectin) was used to measure in vivo activation of platelets. Platelet
      leukocyte aggregates were also determined. Thrombin concentration was assessed by
      the thrombin-antithrombin III complex (TAT) and the fibrinolytic state was
      characterised by the plasmin-alpha2-antiplasmin complex (PAP). Catecholamines
      were measured by means of high-pressure liquid chromatography. CD62p rose from
      baseline (2.3%) to 3.4% and was still elevated after 2 hours (3.1%, p = 0.0133).
      Platelet-leukocyte aggregates were elevated 30 min after exercise (4.3 % vs 3.6%)
      and decreased significantly after 60 min (2.9 %, p = 0.008). TAT increased from
      3.9 microg/l to 8.3 microg/l after competition and to 5.4 microg/l 2 hours later
      (p < 0.001). PAP increased 10-fold from 350 microg/l to 3,267 microg/l after the
      triathlon and was still elevated after 2 hours (1,074 microg/l, p<0.001). No
      linear correlation was found between the hemostatic markers, catecholamines and
      platelet activation. Platelets, coagulation and fibrinolysis are activated by
      competitive exercise in athletes, whereby fibrinolytic changes are pronounced.
      Mechanisms of platelet activation during exercise include phenomena other than
      plasmatic hemostatic factors and catecholamines.

PMID- 11510870
TI  - Influence of continuous and discontinuous training protocols on subcutaneous
      adipose tissue and plasma substrates.
AB  - It has been shown that bouts of high-intensity exercise may reduce subcutaneous
      adipose tissue more than low-intensity exercise. The aim of the present study was
      to examine if a discontinuous training protocol is more successful in reducing
      adipose tissue than a continuous endurance training protocol. Fourteen untrained
      male volunteers were divided into two groups and trained for 10 weeks performing
      3 discontinuous or 3 continuous workouts weekly (discontinuous exercise: 25 times
      80 s 35% VO2max and 40 s 80% VO2max; continuous exercise: 50 min 50% VO2max). The
      discontinuous and the continuous training resulted in a similar subcutaneous
      adipose tissue loss, determined by skinfold measurement, in the leg above the
      patella (-2.4+/-2.4 and -2.4+/-1.4mm, respectively). The normalised plasma
      concentrations of free fatty acid, glycerol, beta-hydroxybutyrate, and lactate
      were similar throughout the final exercise test at the end of the training
      period. Our data suggested that the discontinuous protocol, selected so that the
      average intensity was similar to that of the continuous protocol, was not better
      than the latter in reducing subcutaneous adipose tissue.

PMID- 11510871
TI  - Impact of starting strategy on cycling performance.
AB  - In order to determine an optimal starting technique, the first four-min of two 20
      km time trials (TT) were manipulated. Thirteen competitive, male cyclists (22.7
      +/- 0.8 yr, 180.6 +/- 2.2 cm; 77.1 +/- 2.8kg; 8.3+/-0.7% fat; 4.9+/-0.21 x min(
      1), 71.7+/-1.4% of VO2max) performed three, 20 km TTs. The pace of the first TT
      was self-selected (SS). Min 1-4 of the subsequent, randomly assigned TTs were
      performed 15% below and 15% above the average power output (PO) of min 1-4 of the
      SS TT, subjects then completed the TT as quickly as possible. As a percent change
      from the SS TT, the 15% below TT was (p < 0.05) faster than 15% above TT. Lactic
      acid values at min 4 of the 15% below TT (4.87+/-0.73mM x l(-1)) were lower
      (p<0.05) than both SS TT (9.78+/-1.05mM x l(-1)) and 15% above TT (11.54+/-1.00mM
      x l(-1)). Following min 4 to the finish there were no differences in VE, HR, or
      RPE. However, VO2, VO2 with respect to lactic acid threshold, and PO were all
      elevated in the 15% below TT as compared to both SS TT and 15% above TT. The
      initially high LA resulting from the starting strategies of the SS TT and 15%
      above TT may have reduced the work capacity of active muscle.

PMID- 11510872
TI  - Muscle oxygen desaturation is related to whole body VO2 during cross-country ski
      skating.
AB  - Previous research has demonstrated that blood flow and subsequent O2 desaturation
      (OD) in exercising muscle is related to the static component during exercise. In
      speed skating, increased OD is dissociated from whole body VO2 and heart rate
      (HR) when the skater increases the static component by 'sitting low'. This
      phenomenon was evaluated in cross-country skiers by manipulating speed and
      incline during treadmill roller skiing. Eight male cross-country skiers (22.4 +/-
      3.2 yrs old) randomly performed constant incline- and constant speed-based
      protocols in which increased load was manipulated in five 4min stages by
      treadmill incline or speed change, respectively. A strong relationship (r = 0.83)
      was observed between VO2 and % OD while blood volume change (deltaBV) was
      minimal. Unexpectedly, no HR/ VO2 or HR/OD shifts were observed between
      protocols. The % OD response, in relation to blood lactate values, during
      submaximal exercise was very similar to that of VO2. The lack of an observed
      greater desaturation at higher inclines suggests that the expected static load
      may be attenuated by an increased contribution of poling. The strong relationship
      of % OD to whole body VO2 may be attributed to O2 dissociation in the capillary
      bed of the muscle to meet aerobic energy demand and is independent of blood flow
      dynamics during cross-country ski skating.

PMID- 11510873
TI  - Modification of forearm vascular function following short-term handgrip exercise
      training.
AB  - This study examined the effect of low (25% of maximum voluntary contraction) and
      high (75% of maximum voluntary contraction) intensity short-term handgrip
      exercise training on localized vascular function. Forearm blood flow was
      evaluated in twenty-eight healthy men (age: 23 +/- 4.3) pre- and post-training in
      both forearms at rest, following forearm occlusion and following forearm
      occlusion combined with handgrip exercise using strain gauge plethysmography. The
      4-week program consisted of non-dominant handgrip exercise performed 5 d/wk for
      20 min at either low or high intensity. Following training a significant increase
      in forearm blood flow was noted for the nondominant arm in both groups after
      forearm occlusion (low intensity group: 16.51%; high intensity group: 20.72%; p =
      0.001) and forearm occlusion combined with handgrip exercise (low intensity
      group: 17.71%; high intensity group: 29.27%; p = 0.001). No significant group by
      test interaction (p = 0.632) was found. These data show improved unilateral
      vasodilatory responsiveness after short-term handgrip training. In addition, the
      degree of change is most notable following the greatest vasodilatory stimulus.
      Lastly, a lack of group by treatment interaction suggests the change may be
      independent of training stimulus.

PMID- 11510874
TI  - Urinary caffeine after coffee consumption and heat dehydration.
AB  - This study evaluated the effect of heat-induced dehydration on urinary caffeine
      excretion after the consumption of a strong coffee solution. Following ingestion
      of coffee (caffeine 4.9+/-0.1 [SE] mg/kg, 3-4 cups), ten healthy males were
      intermittently exposed to heat in a sauna until they had lost 2.9 % of lean mass.
      On a separate occasion, they consumed the same amount of coffee but remained
      quiet and euhydrated (control). Urine flow was reduced 7-fold in dehydration. At
      these low excretion rates (< 30 ml/h), caffeine concentration was negatively
      correlated with flow. Peak urinary caffeine (Cmax) was 7.6 +/- 0.4 (SE) microg/ml
      in dehydration and 7.1 +/- 0.2 microg/ml in the control (p > 0.05). Compared with
      the control, dehydration delayed Cmax by 1 hour, maintained higher saliva
      caffeine concentration (6.1 vs 5.2 microg/ml, p < 0.05) and a lower saliva
      paraxanthine/caffeine ratio (p < 0.001). The 24h-recovery of caffeine in urine
      was reduced (1.2 vs 2.8% of dose, p < 0.001), however at least 2.6% of dose were
      lost in sweat. These results suggest that the rise in circulating caffeine due to
      delayed metabolic clearance was partly opposed by a sizeable elimination in
      sweat. Therefore, heat dehydration did not lead to higher concentration of
      caffeine in urine after coffee ingestion.

PMID- 11510875
TI  - Work-related injuries from mandatory fitness training among Swedish firemen.
AB  - A considerable amount of employees incur injuries in professions with mandatory
      on-duty fitness training. The training is necessary for maintaining a good health
      status, physical condition and strength in professions requiring such qualities.
      Injuries in Swedish firemen from on-duty fitness training between 1992 and 1998
      were selected retrospectively from the Information System of Occupational
      Injuries (ISA) at the National Board of Occupational Safety and Health and, if
      having caused a sick-leave exceeding 2 weeks, to the Labour Market Insurance (AMF
      Insurance). The latter comprised injuries from 1995 only. During the seven-year
      period 1,468 injuries from fitness training occurred in male firemen. With an
      estimated 147 h per man and year the injury incidence was 2.6 per 10,000 h of
      exposure. The mean number of days of absence from work was 24.1 days (SD 39.8).
      In 1995, the mean cost per injury for medical treatment was close to 7,000 Euro
      and for production loss almost 4,500 Euro. By far the major part of the injuries,
      75 %, occurred during team and contact sports (primarily floorball and soccer)
      and this sport category also accounted for 83% of the medical costs and 78% of
      the costs for production loss. It is suggested that a restriction of team and
      contact sports as mandatory on-duty fitness training for firemen should be tested
      and evaluated concerning the injury incidence.

PMID- 11510876
TI  - Ice therapy: how good is the evidence?
AB  - Ice, compression and elevation are the basic principles of acute soft tissue
      injury. Few clinicians, however, can give specific evidence based guidance on the
      appropriate duration of each individual treatment session, the frequency of
      application, or the length of the treatment program. The purpose of this
      systematic review is to identify the original literature on cryotherapy in acute
      soft tissue injury and produce evidence based guidance on treatment. A systematic
      literature search was performed using Medline, Embase, SportDiscus and the
      database of the National Sports Medicine Institute (UK) using the key words ice,
      injury, sport, exercise. Temperature change within the muscle depends on the
      method of application, duration of application, initial temperature, and depth of
      subcutaneous fat. The evidence from this systematic review suggests that melting
      iced water applied through a wet towel for repeated periods of 10 minutes is most
      effective. The target temperature is reduction of 10-15 degrees C. Using
      repeated, rather than continuous, ice applications helps sustain reduced muscle
      temperature without compromising the skin and allows the superficial skin
      temperature to return to normal while deeper muscle temperature remains low.
      Reflex activity and motor function are impaired following ice treatment so
      patients may be more susceptible to injury for up to 30 minutes following
      treatment. It is concluded that ice is effective, but should be applied in
      repeated application of 10 minutes to be most effective, avoid side effects, and
      prevent possible further injury.

PMID- 11510877
TI  - Is proprioception altered during loaded knee extension shortly after ACL rupture?
AB  - Knee joint angle reproduction was measured without loading of the quadriceps and
      during concentric quadriceps contractions at 20% of maximal voluntary
      contraction. The threshold of movement detection was measured. The
      reproducibility of the methods and the effect of an acute ACL rupture < 10 wks
      post-injury were examined. A test-retest protocol with a 1 wk hiatus was
      conducted on 15 healthy subjects. Side-to-side differences were tested in 10
      patients with acute ACL rupture. The test-retest protocol did not show any
      significant differences and yielded correlations of r=0.7-0.9 (p<0.01) and
      coefficients of variations of 5.7-13.0%. No side-to-side differences were
      detected in the ACL subjects. Quadriceps loaded; injured 3.96 +/- 2.21 ,
      uninjured 4.7 +/- 1.23, unloaded; injured 2.85 +/- 0.56 degrees, uninjured 2.92+/
      1.20 degrees. Threshold of movement detection; injured 1.48+/-0.81 degrees,
      uninjured 1.44+/-0.65 degrees. Therefore, it may be questioned if the ACL itself
      plays a major role in proprioception performance as it is commonly measured in
      the laboratory.

PMID- 11510878
TI  - Regulation of gene expression by nitric oxide.
AB  - Nitric oxide (NO) modulates transcription factors that bind specific cis
      regulatory DNA responsible for coordinating the spatial and temporal patterns of
      gene expression that are initiated by a changing microenvironment. In this way NO
      helps to orchestrate gene transcription and forms the basis of functional cell
      responses to accommodate metabolic requirements and to coordinate endogenous
      defense mechanisms against a variety of stress and disease conditions. There is
      marked overlap between the signalling pathways triggered by NO, superoxide, and
      hypoxia. Understanding the redox-based regulation of signal transduction and gene
      expression will provide insights into how cell activities are constantly
      coordinated and how promising new therapies may be developed.

PMID- 11510879
TI  - Mechanically induced potentials in rat atrial fibroblasts depend on actin and
      tubulin polymerisation.
AB  - When atrial tissue contracts, mechanically induced potentials (MIPs) are
      generated in fibroblasts, presumably by activation of a non-selective cation
      conductance Gns. Non-stimulated atrial fibroblasts had a mean (+/-SD) membrane
      potential (Em) of -22 +/- 2 mV and an input resistance of 510 +/- 10 MS. MIP
      amplitude (AMIP) was 38+/-4 mV when current injection had polarised Em to Vm = 
      50 mV. The slope of the function relating AMIP to Vm can be regarded as a
      mechanosensitive factor (Xms) that describes the relative increase in Gns during
      a MIP. Putative involvement of cytoskeletal fibres in activation of Gns was
      studied by delivering drugs from the intracellular recording microelectrode.
      Destabilisation of F-actin by 0.2 mM cytochalasin D reduced AMIP from 38 to 16 mV
      and Xms from 5 to 1.8. Destabilisation of tubulin with 0.2 mM colchicine reduced
      AMIP to 21 mV and Xms to 2.1. The combination colchicine plus cytochalasin D
      reduced AMIP to 9 mV and Xms to 1.4. Promoting F-actin stability with exogenous
      adenosine 5'-triphosphate (ATP) increased AMIP and Xms and attenuated the effects
      of cytochalasin D. Similarly, facilitation of tubulin stability with guanosine 5'
      triphosphate (GTP) or taxol increased AMIP and Xms and attenuated the effects of
      colchicine. The results suggest that transfer of mechanical energy from the
      deformed fibroblast surface to the Gns channel protein depends on intact F-actin
      and tubulin fibres.

PMID- 11510880
TI  - Differential gene regulation of renal salt entry pathways by salt load in the
      distal nephron of the rat.
AB  - The aim of the present study was to determine the molecular responses of the main
      salt-reabsorbing systems in the distal nephron to changes of salt load of the
      organism. For this purpose we analysed messenger ribonucleic acid (mRNA) levels
      for the bumetanide-sensitive Na+K+2Cl- cotransporter (BSC1), the thiazide
      sensitive Na+Cl- cotransporter (TSC), the kidney-specific inwards rectifier K+
      channel (ROMK), the amiloride-sensitive epithelial Na+ channel (ENaC) and the
      kidney-specific Cl- channel ClC-K2, in the cortex and inner and outer medulla of
      kidneys from male Sprague-Dawley rats fed a high- (8% w/w), normal- (0.6%) or low
      (0.02%) salt diet or treated chronically with subcutaneous infusions of
      furosemide (12 mg/kg per day). BSC1 and ROMK mRNA levels did not differ between
      the four treatment groups. TSC mRNA increased during furosemide treatment 1.75
      fold versus control but was not affected by a high- or a low-salt diet. The mRNA
      for the alpha-subunit of ENaC increased with the low-salt diet (about 1.5-fold)
      and with furosemide (about 2.1-fold) in all kidney zones, but did not change with
      the high-salt diet. Dietary salt loading down-regulated CIC-K2 mRNA in the outer
      medulla 0.6-fold versus control whilst furosemide treatment, but not the low-salt
      diet, increased ClC-K2 mRNA in the outer (1.6-fold) and inner medulla (2.0-fold).
      These findings suggest that gene expression of Na+ and Cl- entry pathways in the
      distal nephron are at least partly regulated by the salt load of the organism,
      such that salt-reabsorbing systems are stimulated by salt deficiency and
      suppressed by salt overload.

PMID- 11510881
TI  - The role of dopamine-metabolizing enzymes in the regulation of renal sodium
      excretion in the rat.
AB  - The intrarenal natriuretic hormone dopamine (DA) is metabolized by catechol-O
      methyltransferase (COMT) and monoamine oxidase (MAO). We have previously shown
      that inhibition of COMT by entacapone results in a potent D1-like receptor
      mediated natriuretic response. The present study was performed using
      anaesthetized rats to compare the importance of MAO and COMT in DA-mediated
      natriuresis by use of the MAO inhibitor phenelzine. Urinary sodium and DA
      excretion remained unchanged after MAO inhibition, while excretion of the main
      metabolite dihydroxyphenylacetic acid (DOPAC) decreased by 55%. The response was
      unaltered if 5-hydroxytryptamine receptors (5-HT1A) were blocked during MAO
      inhibition. We also investigated the specific renal activities of MAO and COMT in
      rat renal cortex during DA-influenced natriuresis. Specific COMT activity in the
      renal cortex was reduced by 13% after isotonic sodium loading (5% of body mass)
      whereas renal MAO-A and MAO-B activities remained unaltered. Furthermore,
      preliminary data obtained from spontaneously hypertensive rats, whose basal
      urinary DA excretion is higher than that of normotensive Wistar-Kyoto rats, show
      a tendency for renal COMT activity to be lower. It is concluded that
      MAOinhibition by phenelzine does not alter sodium excretion. Furthermore,
      specific renal cortical COMT activity is reduced during partly D1-like receptor
      mediated natriuresis, whereas MAO activity remains unchanged. The results suggest
      that MAO is less important than COMT in regulating DA-mediated natriuresis in the
      rat kidney.

PMID- 11510882
TI  - The coronary endothelium-derived hyperpolarizing factor (EDHF) stimulates
      multiple signalling pathways and proliferation in vascular cells.
AB  - In the present study we determined whether the endothelium-derived
      hyperpolarizing factor (EDHF), in addition to its acute effects on vascular tone,
      activates intracellular signalling pathways other than those associated with Ca2+
      dependent K+ channels. EDHF was generated by rhythmic distension of porcine
      coronary arteries under conditions of combined nitric oxide (NO) synthase/cyclo
      oxygenase blockade, and the EDHF-containing luminal incubate was applied to
      cultured human coronary endothelial or smooth muscle cells. In both cell types,
      the luminal incubate activated tyrosine kinases, the mitogen-activated protein
      (MAP) kinases, extracellular signal regulated kinases 1 and 2 (Erk1/2) and p38,
      as well as protein kinase B/Akt. The constituent responsible for Erk1/2
      phosphorylation was identified as a cytochrome P450 (CYP) metabolite, as Erk1/2
      activation was attenuated by pretreating the EDHF donor with the CYP 2C inhibitor
      sulfaphenazole as well as by CYP 2C antisense oligonucleotides. Erk1/2
      phosphorylation in detector cells was also observed following the transfer of
      supernatant from cultured endothelial cells treated with the CYP inducer beta
      naphthoflavone. The CYP 2C product 11,12-epoxyeicosatrienoic acid (11,12-EET)
      also activated tyrosine kinases, Erk1/2 and p38 MAP kinase. Overexpression of CYP
      2C8 in native porcine coronary artery endothelial cells resulted in an increase
      in endothelial 11,12-EET production and Erk1/2 phosphorylation compared to that
      detected in untreated cells or cells transfected with an antisense CYP 2C8.
      Endothelial cell number was unaffected by transfection with LacZ or CYP 2C8
      antisense but was significantly enhanced in cells overexpressing CYP 2C8. These
      observations indicate that EDHF/11,12-EET is not simply a vasodilator and that
      its continuous release under pulsatile conditions in vivo may affect vascular
      cell signalling and proliferation.

PMID- 11510883
TI  - Hyperbaric oxygenation pretreatment induces catalase and reduces infarct size in
      ischemic rat myocardium.
AB  - Ischemia-reperfusion injury is a major complication occurring in heart stroke,
      cardiopulmonary bypass surgeries, and heart transplantation. Reactive oxygen
      species generated during the reperfusion phase overwhelm the scavenging
      capacities of antioxidant enzymes, and result in oxidative damage to the
      myocardium. We examined whether hyperbaric oxygenation (HBO) pretreatment induces
      antioxidant enzymes and protects the heart from subsequent ischemia-reperfusion
      injury. Rats were intermittently exposed to 100% O2 at 3 ATA (where ATA is
      absolute atmosphere) for 1 h daily and then sacrificed after 24 h of recovery in
      room air. Isolated hearts were subjected to 40 min of ischemia and 90 min of
      reperfusion. HBO pretreatment was found to condition the heart and enhance
      enzymatic activity and gene expression of catalase, thereby significantly
      reducing infarct size after reperfusion. A catalase inhibitor, 3-amino-1,2,4
      triazole, completely abolished the infarct-limiting effect of HBO pretreatment,
      which suggests that HBO-induced tolerance against ischemia-reperfusion injury is
      due to catalase induction. Our results imply that HBO preconditioning may be
      developed as a new preventive measure for reperfusion injury in the heart.

PMID- 11510884
TI  - Cytokines and cytokine inducers stimulate prostaglandin E2 entry into the brain.
AB  - Cytokine inducers and cytokines increase the circulating level of prostaglandin
      E2 (PGE2) during the acute-phase immune response. This occurs simultaneously with
      the onset of fever, indicating that brain levels of PGE2 also increase. This
      raises the possibility that PGE2 produced in the peripheral circulation, not
      necessarily at distant sites from the brain, may penetrate the brain and be
      present in the cerebrospinal fluid (CSF). Blood and CSF levels of PGE2 in rabbits
      were measured by radioimmunoassay during fever stimulated in response to
      lipopolysaccharide (LPS), polyinosinic:polycytidylic acid (poly I:C) and
      interleukin-1 (IL-1) given i.v. The effect of the prostaglandin synthesis
      inhibitor ketoprofen on these parameters was also studied. In addition, the level
      of radioactivity in the CSF was measured following the administration of [125I]
      labelled PGE2 i.v. during fever induced by LPS, poly I:C, IL-1 or tumor necrosis
      factor alpha (TNFalpha). Both LPS and poly I:C stimulated an increase in plasma
      and CSF levels of PGE2 over a 5-h period with a peak at 60 min and 90 min,
      respectively, which occurred in parallel with the changes in body temperature.
      Ketoprofen abolished the rise in plasma and CSF PGE2 levels and the rise in body
      temperature in response to LPS, poly I:C and IL-1. In experiments where animals
      were given [125I]-labelled PGE2 i.v., radioactivity well above the background
      level was measured in samples of CSF collected from LPS-, poly I:C-, IL-1- or
      TNFalpha-pretreated animals. In contrast the radioactivity present in samples of
      CSF perfusate collected from control (saline-treated) animals was
      indistinguishable from the background level. These data indicate that cytokine
      inducers and cytokines increase the mass level of PGE2 in blood and CSF and also
      increases the entry, from the peripheral circulation, of radiolabelled PGE2 into
      the third cerebral ventricle.

PMID- 11510885
TI  - Cu2+ reveals amiloride-induced activation and blocking of non-selective cation
      channel in larval bullfrog skin.
AB  - The non-selective cation channel (NSCC) in the larval bullfrog skin contributes
      to the short-circuit current (SCC) across the skin. The effects of amiloride and
      acetylcholine on the SCC were examined in the presence or absence of Cu2+ to
      determine whether the amiloride binding site mediating activation or that
      mediating inhibition of the channel is blocked by Cu2+ and whether amiloride and
      acetylcholine share a common binding site on the NSCC. The skin of tadpoles
      raised in aldosterone was examined with K-Ringer present on the apical side to
      potentiate the SCC. Amiloride (10(-4) M) transiently increased SCC in the absence
      of Cu2+. Apical application of 500 microM Cu2+ increased the SCC. In the presence
      of Cu2+, amiloride decreased the SCC. In contrast, acetylcholine (1 mM)
      transiently increased SCC whether Cu2+ was present or not. These results suggest
      that there are two binding sites for amiloride on the NSCC, whereby the site that
      activates the channel is blocked by Cu2+ while the site that inhibits it is not,
      and that the binding sites for acetylcholine and amiloride may be different.

PMID- 11510886
TI  - Glucagon attenuates the action of insulin on glucose output in the liver of the
      Goto-Kakizaki rat perfused in situ.
AB  - The effects of glucagon and insulin on glucose production were explored directly
      using the isolated perfused liver of the Goto-Kakizaki (GK) rat, an animal model
      of type-2 diabetes. In the perfused liver of control rats, infusion of glucagon
      (0.06-1.0 nM) into the portal vein dose-dependently increased glucose output. In
      the GK rat liver, in which the intracellular distribution of glycogen was
      heterogeneous, basal glucose output during perfusion was significantly higher
      than in control, whereas the effect of glucagon on the maximum glucose output was
      not different. Infusion of insulin inhibited the glucagon-induced hepatic glucose
      output by 30-40% in control livers, but had no effect on that from the GK rat
      liver. The increase in hepatic cAMP content after glucagon infusion was
      antagonized by insulin in control livers, but not in the livers of GK rats. These
      results indicate that the antagonistic effect of insulin on glucagon-induced
      hepatic glucose production was attenuated in the isolated liver of the GK rat and
      suggest that this insulin resistance appeared in the signal transduction process
      of glucagon upstream from cAMP production.

PMID- 11510887
TI  - The transmission efficiency of backward walking at different gradients.
AB  - The specialized design of the bipedal system towards forward locomotion has been
      assessed by measuring the metabolic cost and the mechanical work of both forward
      and backward walking on a treadmill at seven gradients from 0 to +32%. With
      respect to forward locomotion, backward walking implies: (1) a higher metabolic
      cost particularly at level gradient, while at steeper inclines the difference
      decreases, (2) the same mechanical internal work despite an increased stride
      frequency, (3) higher mechanical external work within a gradient range from 0 to
      +15%, (4) lower "energy recovery", i.e. the ability to save mechanical energy by
      moving as an inverted pendulum, mainly in level walking, and (5) as a consequence
      of the above results, a decrease of the efficiency of locomotion particularly at
      the 0% gradient. The transmission efficiency of backward walking, relative to the
      forward progression, was found to be about 65% in level locomotion, while at
      higher gradients it increased to and was maintained at a value of about 93%. The
      poorer economy of level backward walking could also be explained by an impaired
      elastic contribution in the last part of the double contact phase, while the
      similarity of the two gaits on higher gradients is caused by disruption of the
      pendulum-like paradigm due to the trajectory geometry of the body's centre of
      mass progressively losing its downward portion.

PMID- 11510888
TI  - Characterization of action potential waveform-evoked L-type calcium currents in
      pituitary GH3 cells.
AB  - The response of the L-type Ca2+ current (ICa,L) in pituitary GH3 cells to
      variations in the action potential (AP) waveform was examined using the whole
      cell configuration of the patch-clamp technique. ICa,L evoked during an AP
      waveform exhibited an early and a late component. The early component occurred on
      the rising phase of the AP; the late component coincided with the falling phase.
      Prolonging the falling phase of the AP increased the Ca2+ charge carried by
      ICa,L, although the amplitude of the late ICa,L was reduced. Prolonging the peak
      voltage of the AP waveform, however, increased the amplitude of the late
      component. ICa,L inactivated during a train of AP waveforms. When Ba2+ was used
      as the charge carrier, current inactivation during a train of APs decreased.
      Likewise, ICa,L evoked by the AP templates with irregular bursting pattern was
      inactivated. When the repetitive firing of APs with depolarizing potentials was
      replayed to cells, Ca2+ entry was not only spread over the entire AP, but also
      occurred during the interspike voltage trajectory. After application of
      thyrotropin releasing hormone (TRH; 10 microM), ICa,L in response to rectangular
      pulses was increased and the current/voltage relation shifted slightly to more
      negative values. TRH (10 microM), thapsigargin (10 microM) or cyclopiazonic acid
      (30 microM) enhanced the late component of the AP-evoked ICa,L. TRH also
      attenuated the inactivation of ICa,L during a train of APs. These results
      indicate that in pituitary GH3 cells, the time course and kinetics of ICa,L
      during the AP waveforms is distinct from that evoked by rectangular voltage
      clamp. Changes in the shape and firing pattern of APs in GH3 cells can modulate
      Ca2+ influx through L-type Ca2+ channels. Ca2+ release from internal stores may
      affect the magnitude of AP-evoked ICa,L in these cells.

PMID- 11510889
TI  - Influence of 72% injury in one kidney on several organs involved in guanidino
      compound metabolism: a time course study.
AB  - Arginine (Arg) produced from citrulline originates mostly from kidneys. Arg is
      involved in guanidino compound biosynthesis, which requires interorgan co
      operation. In renal insufficiency, citrulline accumulates in the plasma in
      proportion to renal damage. Thus, disturbances in Arg and guanidino compound
      metabolism are expected in several tissues. An original use of the model of
      nephrectomy based on ligating branches of the renal artery allowed us to
      investigate Arg and guanidino compound metabolism simultaneously in injured
      (left) and healthy (right) kidneys. The left kidney of adult rats was subjected
      to 72% nephrectomy. Non-operated, sham-operated and nephrectomized rats were
      studied for a period of 21 days. Constant renal growth was observed only in the
      healthy kidneys. Guanidino compound levels were modified transiently during the
      first 48 h. The metabolism and/or tissue content of several guanidino compounds
      were disturbed throughout the experimental period. Arg synthesis was greatly
      reduced in the injured kidney, while it increased in the healthy kidney. The
      renal production of guanidinoacetic acid decreased in the injured kidney and its
      urinary excretion was reduced. The experimentally proven toxins alpha-keto-delta
      guanidinovaleric acid and guanidinosuccinic acid (GSA) accumulated only in the
      injured kidney. The urinary excretion of GSA and methylguanidine increased in
      nephrectomized rats. When the injured kidney grew again, the level of some
      guanidino compounds tended to normalize. Nephrectomy affected the guanidino
      compound levels and metabolism in muscles and liver. In conclusion, the specific
      accumulation of toxic guanidino compounds in the injured kidney reflects
      disturbances in renal metabolism and function. The healthy kidney compensates for
      the injured kidney's loss of metabolic functions (e.g. Arg: production). This
      model is excellent for investigating renal metabolism when a disease destroys a
      limited area in one kidney, as is observed in patients.

PMID- 11510890
TI  - Expression of the Na+K+-2CI- cotransporter in alpha and beta cells isolated from
      the rat pancreas.
AB  - The expression of the Na+-K+-2Cl- cotransporter (NKCC1) in alpha cells and beta
      cells from the rat pancreas was examined. Isolated alpha cells and beta cells in
      a mixed islet cell preparation were identified by volume using video-imaging
      methods, and by the expression of glucagon or insulin. The expression of mRNA for
      NKCC1 in pancreatic islets was demonstrated by RT-PCR. Immunocytochemical studies
      showed that the NKCCI protein was expressed in rat beta cells, but not alpha
      cells. The activity of Na+-K+-2Cl- cotransporter was also examined, by studying
      cell volume regulation in response to HEPES-buffered, hypertonic solutions. A
      regulatory volume increase was observed in the beta cells but not the alpha
      cells. It is concluded that the NKCC1 is expressed in rat pancreatic beta cells
      but not alpha cells. This is consistent with the hypothesis that Cl- is
      accumulated above the expected equilibrium distribution in beta cells, but is
      below equilibrium in alpha cells.

PMID- 11510891
TI  - Ca2+ channels in clonal rat anterior pituitary cells (GH3/B6).
AB  - In clonal rat somatomammotroph cells (GH3/ B6) Ca2+ influx through voltage
      dependent Ca2+ channels is important for regulating the Ca2+ concentration that
      mediates hormone secretion. To study the Ca2+ channel subtypes in GH3/B6 cells,
      Ca2+ channel currents were recorded with the whole-cell configuration of the
      patch-clamp technique using Ba2+ as the charge carrier. Forty-nine percent of the
      total Ba2+ current amplitude was mediated by a nifedipine-sensitive current (L
      type). In addition, three other high-voltage-activated Ca2+ channel current
      components could be distinguished pharmacologically: 10 nM omega-agatoxin-IVA
      sensitive current (22%; P-type), omega-conotoxin-MVIIC-sensitive current (18%; Q
      type), and toxin-resistant current (24%). Since omega-conotoxin GVIA (2 microM)
      had no blocking effect, N-type Ca2+ channels are assumed not to be present in
      GH3/B6 cells. The T-type Ca2+ channel current was either absent or very small.
      Different pore-forming alpha1 subunits of Ca2+ channels were found to be
      expressed in GH3/B6 cells, which could be the molecular correlates of the
      different Ba2+ current subtypes: alpha1G of T-type, alpha1C, alpha1D and alpha1S
      of L-type, and alpha1A of P/Q-type current. In addition, transcripts for beta1,
      beta2 and beta3 subunits were detected. Blockage of L-type channels with 10
      microM nifedipine or P/Q-type channels with 10 nM omega-agatoxin MVIIC + 200 nM
      omega-conotoxin blocked action potential firing in GH3/B6 cells and decreased
      basal prolactin secretion.

PMID- 11510892
TI  - Breath-holding time: effects of non-chemical factors in divers and non-divers.
AB  - Two main factors (chemical and non-chemical factors) are involved in the
      determination of breath-holding time (BHT). Earlier studies have shown that
      chemical factors can be modified by training. The aim of this study was to
      establish whether BHT can be lengthened or shortened by changes in non-chemical
      factors according to the degree of training of the divers. Hyperoxic hypercapnic
      rebreathing challenges interrupted by different periods of voluntary apnoea (20,
      40 and 50 s) were performed by divers (n=8) and non-divers (n=6). The
      relationships between ventilation (VE) and end-tidal PCO2 and mean inspiratory
      flow (VT/TI) where VT is the tidal volume and TI the inspiration time) and end
      tidal PCO2 were measured before (pre) and after (post) apnoea for each
      population. The slopes of these linear regressions (VEs and VT/TI,s,
      respectively) reflected respiratory centre activity. VFs-post and VT/TIs-post
      increased with BHT and were higher in the non-divers than in divers. There were
      no significant differences between VFs-pre and VFs-post or between VT/TIs,-pre
      and VT/TIs-post in divers for all BHT. However, in non-divers, significant
      differences between pre and post values appeared at 20, 40 and 50 s for VT/TI,s
      and at 40 and 50 s for VEs. Non-chemical factorswere obtained by calculating the
      differences between pre and post values and were different at 20 and 40 s for VEs
      (P<0.05) and for all BHT for VT/TI,s (P<0.05). The non-chemical factors increased
      significantly with BHT and were higher in the non-divers. These adaptations in
      divers may modify the breath-hold breaking point and consequently increase BHT.

PMID- 11510893
TI  - The Na+-activated K+ channel contributes to K+ efflux in Na+-loaded guinea-pig
      but not rat ventricular myocytes.
AB  - Activation of the Na+-activated K+ channels (KNa channels) has been suggested to
      contribute to the ischaemia-induced accumulation of extracellular K+ (K+e) in the
      mammalian myocardium. Recent evidence shows that these channels are not present
      in rat ventricular myocytes [9]. We have therefore investigated the effect of
      raised intracellular Na+ activity (aiNa) on intracellular K+ activity (aiK) in
      guinea-pig myocytes, which possess the channels, and on rat ventricular myocytes
      which do not. The Na+-activated K+ current was activated by an increase in aiNa
      induced by removing extracellular Ca2+ and Mg2+ and inhibiting the Na-pump. The
      aiNa increased and the aiK decreased in both guinea-pig and rat myocytes
      superfused with Ca2+- and Mg2+-free Tyrode. The new steady-state increase in aiNa
      and decline in aiK were similar in both species. Inhibition of the Na-pump
      resulted in an additional increase in aiNa and decrease in aiK in both species.
      However, both the increase in aiNa and decrease in aiK were greater in guinea-pig
      myocytes and the decline in aiK in guinea-pig myocytes followed the development
      of a large Na+-activated K+ current. When Li+ replaced Na+ in the superfusate the
      Na+-activated K+ current did not develop and the fall in aiK was reduced. In Na+
      loaded rat myocytes, which do not have a Na+-activated K+ current, the decline in
      aiK was reduced and blocked by 2 mM Mg2+ suggesting that a Mg2+-sensitive non
      specific cation channel may be involved in the K+ efflux from rat myocytes [12].
      These data suggest that KNa channels are a major route for K+ efflux from Na+
      loaded guinea-pig myocytes.

PMID- 11510894
TI  - Fatty acids inhibit anion secretion in rat colon: apical and basolateral action
      sites.
AB  - Ca2+-dependent secretagogues evoke only a transient Cl- secretion in intestinal
      epithelia, although they induce a prolonged increase in the intracellular Ca2+
      concentration, suggesting that they may exert an additional antisecretory action.
      In order to study the mechanism of this antisecretory effect, Cl- secretion,
      measured as the increase in short-circuit current (Isc), was evoked by carbachol
      in the absence and presence of different inhibitors. Neither a calmodulin
      antagonist, calmidazolium, nor different inhibitors of the nitric oxide (NO)
      pathway, i.e. Nomega-nitro-L-arginine (L-NNA) and Nomega-nitro-L-arginine
      methylester (L-NAME), affected the carbachol-induced Isc. However, inhibition of
      phospholipases A2 (PLA2) by quinacrine or arachidonyltrifluoromethyl ketone
      (AACOCF3) enhanced the Isc response evoked by carbachol, suggesting a role of
      fatty acids in the downregulation of anion secretion. Neither econazole, a
      cytochrome P450 inhibitor, nor nordihydroguaiaretic acid (NDGA), an inhibitor of
      lipoxygenases, mimicked the action of the PLA2 blockers. Conversely, short- or
      medium-chain fatty acids inhibited the carbachol- and forskolin-induced Isc with
      caprate (C10:0) being the most efficient water-soluble fatty acid. This fatty
      acid inhibited a Cl- current, which was driven across the apical membrane by a
      serosally to mucosally directed Cl- gradient after depolarization of the
      basolateral membrane. A second action site of fatty acids seems to be the
      basolateral membrane. After permeabilization of the apical membrane with the
      ionophore nystatin, a mucosally to serosally directed K+ gradient induced a K+
      current, which was also inhibited by caprate. These results indicate that
      carbachol not only acts as a secretagogue but at the same time initializes
      downregulation by increasing the intracellular concentration of fatty acids, a
      mechanism limiting the resulting Cl- secretion.

PMID- 11510896
TI  - Modulation of the volume-sensitive K+ current in Ehrlich ascites tumour cells by
      pH.
AB  - The effects of extracellular and intracellular pH (pHo and pHi respectively) on
      the regulatory volume decrease (RVD) response and on the volume-sensitive K+ and
      Cl- currents (IK,vol and ICl,vol respectively) were studied in Ehrlich ascites
      tumour cells. Alkaline pHo accelerated and acidic pHo decelerated the RVD
      response significantly. Intra- and extracellular alkalinisation increased the
      amplitude of IK,vol whereas acidification had an inhibitory effect. The magnitude
      of ICl,vol was not affected by changes in pHi or pHo. A significant reduction in
      the activation time for IK,vol after hypotonic cell swelling was observed upon
      moderate intracellular alkalinisation (to pHi 7.9). A further increase in pHi to
      8.4 resulted in the spontaneous activation of an IK under isotonic conditions
      which resembled IK,vol with respect to its pharmacological profile and
      current/voltage (I/V) relation. Noise analysis demonstrated that the increased
      amplitude of IK,vol at alkaline pH resulted mainly from an increase in the number
      of channels (N) contributing to the current. The channel open probability, Po,
      was largely unaffected by pH. The pH dependence and the biophysical and
      pharmacological properties of IK,vol are similar to those of the cloned tandem
      pore-domain acid-sensitive K+ (TASK) channels, and in the current study the
      presence of TASK-1 was confirmed in Ehrlich cells.

PMID- 11510895
TI  - Hyperosmotic shock induces both activation and translocation of glucose
      transporters in mammalian cells.
AB  - The effect of osmotic stress on sugar transport was investigated in Clone 9
      epithelial cells, which express the glucose uniporter GLUT1, and in 3T3-L1
      adipocytes, which express both GLUT1 and GLUT4. An acute hyperosmotic shock
      increased the uptake of sugars in both cell types. In Clone 9 cells, this was
      followed by a regulatory volume increase (RVI) response. Stimulation of transport
      was rapid and reversible, with half-lives (t 1/2) for stimulation of 2-deoxy-D
      glucose uptake of 5.6 +/- 0.9 (n=6) and 22.7 +/- 1.5 (n=4) min for Clone 9 cells
      and adipocytes respectively. The effect was dose dependent, reaching a maximum at
      1.1 osM of 2.9 +/- 0.1-fold (n=3) for Clone 9 cells and 8.2 +/- 0.8-fold (n=3)
      for adipocytes. In the latter, this stimulation correlated with translocation of
      the glucose transporter isoform GLUT4 to the cell surface and was not
      significantly different from that elicited by 160 nM insulin (7.6 +/- 1.2-fold,
      n=3). The effect of osmotic shock was not, however, influenced by inhibitors of
      either phosphoinositide 3-kinase (PI 3-kinase) (wortmannin, 250 nM) or of p38
      mitogen-activated protein kinase (p38 MAP kinase) (SB203580, 20 microM), which
      reportedly prevent GLUT4 translocation and/or activation by insulin respectively.
      These inhibitors also had no effect on the stimulation of transport by osmotic
      shock in Clone 9 cells. However, in contrast to adipocytes, the effect of osmotic
      shock on glucose transport in Clone 9 cells reflected primarily a change in the
      intrinsic activity of cell surface transporters and there was only a minor change
      in their subcellular distribution as assessed by cell immunostaining or no change
      as assessed by surface biotinylation. These results indicate that the response of
      cells to osmotic shock can involve changes both in transporter activity and
      location. The signal transduction pathways involved include neither PI 3-kinase
      nor the classical, osmotically-activated component, p38 MAP kinase.

PMID- 11510897
TI  - Whole-cell patch-clamp: true perforated or spontaneous conventional recordings?
AB  - Perforated whole-cell patch-clamp recordings obtained with nystatin are
      frequently used to preserve intracellular integrity. However, the perforated
      patch configuration may sometimes undergo a spontaneous change into the
      conventional whole-cell configuration, especially when lymphocytes are
      investigated. The electrophysiological criteria-- previously described--for
      establishing the existence of the perforated whole-cell configuration have been
      shown to be insufficient. Thus, the dye eosin, applied to the pipette solution,
      was tested as a tool for discriminating between the perforated and the
      conventional whole-cell configurations on rat T-lymphocytes. The dye never
      entered the cell from the pipette during the entire measurement in the perforated
      whole-cell configuration. In contrast, all cells in the conventional whole-cell
      configuration became red immediately after membrane rupture. Eosin barely changed
      the currents studied. The results suggest that eosin is a dye of choice for
      verifying a true perforated-patch configuration.

PMID- 11510898
TI  - Hip arthropathy associated with hemodialysis. Radiological and laboratory
      evaluation of 56 hemodialysis patients.
AB  - There were 56 consecutive patients enrolled in our study from the outpatient
      clinic of our institution, mean age of 59 years, who had been on hemodialysis for
      2-26 years. The duration of hemodialysis was less than 10 years for 36 patients
      (short-term group) and 10 years or more for 20 patients (long-term group) with a
      mean duration of 11 years at time of the investigation. In the short-term group,
      plain radiography revealed bone cysts in 9 hips (17%) and joint space narrowing
      in 10 hips (19%), while in the long-term group, there were bone cysts in 19 hips
      (48%) and joint space narrowing in 6 hips (15%). Bone mineral density as
      determined by dual-energy X-ray absorptiometry was 0.621 g/cm2 for patients in
      the short-term group and 0.503 g/cm2 for patients in the long-term group. Hip
      arthroplasties were performed in 3 patients suffering from femoral neck fracture
      due to bone cysts. All of them showed marked bone loss (mean 0.380 g/cm2). In
      conclusion, plain radiography and dual-energy X-ray absorptiometry are useful for
      evaluating the hip arthropathy of hemodialysis patients, especially those who
      have undergone long-term hemodialysis.

PMID- 11510899
TI  - Recovery after carpal tunnel syndrome operation: the influence of the opposite
      hand, if operated on in the same session.
AB  - In a clinical, retrospectively randomised study, we compared the results of the
      operation for a carpal tunnel syndrome when one side only or both sides were
      simultaneously assessed in one session. Of the 125 patients examined, 47.2% had
      both hands operated on in one session, 52.8% had only one hand operated on in one
      session or both hands in two sessions. We found the bilateral simultaneous
      operation to be associated with better results concerning earlier return to work,
      earlier relief of symptoms and better patient satisfaction than the operation on
      one side only. These are explained by the necessity of using both hands for daily
      activities and thus a guaranteed functional follow-up treatment after the
      bilateral operation. In conclusion, we propose operating on both hands
      simultaneously whenever possible, even if the opposite hand presents with only a
      slight CTS, which would otherwise not be considered for operation yet.

PMID- 11510900
TI  - On the impact of calcified deposits within the rotator cuff tendons in shoulders
      of patients with shoulder pain and dysfunction.
AB  - We wanted to prove the hypothesis that calcified deposits within the rotator cuff
      tendons are merely an epiphenomenon of complex morphological alterations in the
      shoulders of patients with shoulder pain and dysfunction. The shoulders of 92
      patients with calcified deposits within the rotator cuff tendons as noted on
      plain radiographs were investigated by means of magnetic resonance imaging (MRI;
      mean age of patient 51.1 years), as well as the shoulders of 28 age- and sex
      matched patients with similar clinical symptoms but without any signs of such
      calcified deposits on plain radiographs. The MRI protocol comprised a coronal,
      oblique, T1-weighted, spin-echo sequence, a T2-weighted, turbo spin-echo
      sequence, a sagittal, oblique, T2-weighted, turbo spin-echo sequence, and an
      axial, T1-weighted, spin-echo sequence. Furthermore, a coronal, oblique, short
      tau-inversion recovery sequence and a gradient echo sequence were used. The
      results were compared with data from healthy, asymptomatic volunteers as reported
      in the literature. The MRI investigations showed no substantial differences
      between patients with or without calcified deposits within the rotator cuff
      tendons, but distinct differences between such patients and healthy, asymptomatic
      volunteers. For patients with shoulder pain, shoulder dysfunction, and calcified
      deposits within the rotator cuff tendons, these calcified deposits are most
      probably not the main cause of the clinical symptoms. Rather, it seems to be
      useful to consider the results of MRI investigations whenever planning
      therapeutic procedures for patients with shoulder pain and dysfunction,
      irrespective of whether or not there are signs of calcified deposits within the
      rotator cuff tendons on plain radiographs.

PMID- 11510901
TI  - Extracorporeal shock-wave therapy for chronic lateral tennis elbow--prediction of
      outcome by imaging.
AB  - Today the clinical use of extracorporeal shockwave application (ESWA) for the
      treatment of lateral tennis elbow is hampered by the lack of results from
      randomized controlled trials and of predictive parameters of clinical outcome.
      The present prospective study aimed to provide the latter by means of magnetic
      resonance imaging (MRI). Twenty-three female and 19 male patients with unilateral
      chronic tennis elbow of the dominant site were clinically examined before and
      after repetitive low-energy ESWA. MRI was performed before ESWA to evaluate
      signal intensity changes or contrast enhancement of the common extensor tendon
      and the lateral epicondyle. After ESWA (mean follow-up period 18.6 months for all
      patients), clinical evaluation showed a significantly better mean clinical
      performance after ESWA than before treatment. Interestingly, male patients showed
      a significantly better mean clinical performance after ESWA than female patients,
      and male and female patients differed significantly in the signal intensity of
      the common extension tendon cross-section and tendon thickening on MRI. For
      female patients, MRI scans could be applied for predicting a positive clinical
      outcome of ESWA. This study reports the first indication of predictability of
      positive clinical outcome of the treatment of chronic lateral tennis elbow by
      ESWA using imaging prior to treatment. This may serve as an important step
      towards overcoming the therapeutic nihilism with respect to the non-operative
      management of this condition recently in the literature.

PMID- 11510902
TI  - Radiographic evaluation of cervical spine trauma. Plain radiography and
      conventional tomography versus computed tomography.
AB  - Different imaging modalities are available for the diagnosis of cervical spine
      injuries. There is a controversial discussion about whether plain radiography
      (PR), conventional tomography (CTO) or computed tomography (CT) should primarily
      be used. PR and CTO are more often available and less costly than CT. Especially
      in second-care hospitals, CT is not always available. The diagnostic work-up in
      these centres has to rely on conventional techniques. The aim of this study was
      to define the role of PR supplemented by CTO in the diagnosis of cervical spine
      trauma in comparison to CT. Twenty-five patients were identified who underwent
      plain radiography (PR), conventional tomography (CTO) and computed tomography
      (CT) for the diagnosis of a cervical fracture. In 19 patients a fracture of the
      cervical spine was identified. All images were reviewed by two independent
      observers to estimate the interobserver variability. The highest detection rate
      was achieved by CT (18/18 fractures detected for observer 1/2), followed by CTO
      (16/16 fractures) and then PR (15/14 fractures). When the detection rates of PR
      and CTO are combined, 18 fractures were detected by each of the observers. The
      results were analysed for the dens and the rest of the cervical spine
      independently. For PR and CTO the detection rates were lower for fractures of the
      dens than for the rest of the cervical spine. We conclude that the combination of
      PR and CTO accurately detects fractures of the cervical spine compared with CT.
      If a fracture of the dens is suspected, the patients should be referred to CT due
      to its superior accuracy in this region.

PMID- 11510903
TI  - Conservative treatment for trigger thumb in children.
AB  - Conservative treatment was performed for 60 trigger thumbs (19 right, 17 left, 12
      bilateral) in 48 children (19 boys, 29 girls); the age at initial diagnosis
      ranged from 0 to 48 months old (mean 26 months). In this approach, only passive
      exercise of the affected thumb was performed by the mother. As a result, two
      patients (two thumbs) dropped out of treatment. Fifty-six thumbs out of 58 showed
      a satisfactory result (96%). Sixteen thumbs (in stage 2) and eight thumbs (in
      stage 3) showed completely recovery. Four thumbs (in stage 3) have not yet
      improved. In conclusion, we suggest that conservative treatment is effective for
      trigger thumbs in stage 2, while surgical therapy was thought to be indicated for
      stage 3 before the age of 3 years to avoid flexion deformity.

PMID- 11510904
TI  - Nine-year results of Muller cemented titanium Straight Stems in total hip
      replacement.
AB  - At the Orthopaedic Department of the University of Basel, a total of 540 cemented
      Muller titanium alloy (Ti6Al7Nb) Straight Stems were inserted between 1989 and
      1993. A cohort of 120 consecutive patients (66 women, 54 men) with 126 prostheses
      operated on between March and December 1989 were followed clinically and
      radiologically in a prospective manner for a mean observation time of 9.1 years.
      In all cases, the Muller titanium alloy Straight Stem was combined with the
      senior author's (E.W.M.) Press-Fit Cup. The mean age of the patients at surgery
      was 66 (range 43-93) years. Fourty patients (41 hips) died, 9 were interviewed by
      telephone, none was 'lost to follow-up'. Seventy-one patients with 76 hip
      replacements were available for the follow-up. Four hips had been revised: two of
      them due to aseptic loosening of the femoral component, one because of a late
      infection--all after 9 years--and one owing to a periprosthetic fracture after 6
      years. The 9-year overall survivorship is 96.8%, and for aseptic loosening of the
      stem 98.4%. None of the cups had to be revised for aseptic loosening. The
      clinical result (according to Merle d'Aubigne) was excellent and good in 88%,
      moderate in 8%, and poor in 4%. The radiological analysis showed no osteolysis or
      radiolucent lines in 59 prostheses (78%). Nine stems (12%) showed a radiolucent
      line. Focal osteolysis was detected in 8 cases (10%) in one or more Gruen zones.
      The distribution of the osteolyses shows that predominantly zones VII, VI, V, and
      II are affected in decreasing frequency. No osteolysis was detected on the
      acetabular side. Our results do not confirm the high rate of osteolysis and
      revisions with the Muller titanium alloy Straight Stem presented by some other
      institutions. The verdict on a specific endoprosthetic implant must be made by
      combined assessment of the design, the implant surface condition, the material,
      the cement, the cementing procedure and the operative technique. The statement
      made in earlier publications that cemented titanium alloy should not be used as a
      femoral stem prosthesis should be reconsidered.

PMID- 11510905
TI  - Intracellular measurement of polyethylene particles. A histomorphometric study.
AB  - A histological and histomorphometric study was carried out on pseudo-capsules
      retrieved from patients during revision surgery of cementless total hip
      replacement. Polyethylene loading and areal polyethylene particle size in
      different cells of the reticuloendothelial cell line were determined within the
      tissue by histomorphometry. In the reticuloendothelial cell line, foreign-body
      giant cells are considered to be the result of confluence of mononuclear
      macrophages caused by large particles or other unknown stimuli. The aim of this
      study was to investigate whether polyethylene particle size and polyethylene
      loading are different in mononuclear macrophages and foreign-body giant cells.
      The specimens were examined under the light-optical microscope with plain and
      polarized light. The polyethylene loading of 329 macrophages (mononuclear), 81
      small foreign-body giant cells (2-5 visible nuclei), and 103 large foreign-body
      giant cells (6 or more visible nuclei) was determined and the intracellular
      polyethylene particle size analyzed by histomorphometry. The mean polyethylene
      loading was 13 +/- 8 microm2, 25 +/- 16 microm2, and 49 +/- 42 microm2,
      respectively. This difference was statistically significant (Student's t-test, P
      < 0.05). The mean polyethylene particle size was 2.34 +/- 3.2 microm2, 3.02 +/-
      3.46 microm2, and 4.70 +/- 11.25 microm2, respectively. This difference was
      statistically significant between macrophages and large foreign-body giant cells
      (t-test, P < 0.05). The findings of this light-optical study show that the mean
      intracellular polyethylene particle size is greater in foreign-body giant cells.
      In addition, absolute polyethylene loading tends to be higher in foreign-body
      giant cells than in mononuclear macrophages.

PMID- 11510906
TI  - X-ray photoelectron spectroscopy studies on adsorption of amino acids from
      aqueous solutions onto oxidised titanium surfaces.
AB  - Osseointegration is concerned with processes at the cellular level. However, the
      titanium surface is also capable of interactions with organic structures at the
      molecular level. These properties of titanium are presented from a
      physicochemical viewpoint. Adsorption experiments are described that should
      simulate molecular processes in the organism. The selected model substances,
      amino acids, were adsorbed from aqueous saline solutions with various pH values
      onto evaporated titanium layers. The evidence of adsorbates was determined by
      photoelectron spectroscopy. The pH values at which adsorption occurred, the
      binding energies and signal intensities according to curve fit allow conclusions
      to be drawn from the adsorption reactions. Thus, the titanium surface
      preferentially forms a surface complex with the carboxyl groups of the amino
      acids in an acidic solution. The resulting positions of the adsorbed molecules
      can be confirmed through evaluation of the line intensities. The results show
      clearly that there is chemical bonding between the titanium surface and the
      organic substances. Assuming that a comparable situation occurs in the organism,
      such processes or similar ones can be viewed as preliminary stages of
      osseointegration.

PMID- 11510907
TI  - Serum acid phosphatase as a tumour marker in giant cell tumour of bone.
AB  - The serum acid phosphatase value was examined in nine patients with giant cell
      tumour of bone. Five showed a high level of acid phosphatase, which fell to
      within normal limits after surgery. Although the remaining four patients showed a
      normal acid phosphatase level before surgery, the postoperative acid phosphatase
      level was lower than the preoperative level in each case. Therefore, it is
      strongly suggested that serum acid phosphatase is a useful tumour marker in
      diagnosing giant cell tumour of bone as well as in evaluating the efficacy of
      treatment.

PMID- 11510908
TI  - Immunolocalization of the angiogenetic factor pleiotrophin (PTN) in the growth
      plate of mice.
AB  - The aim of this study was to find out whether and where the angiogenic agent
      pleiotrophin (PTN) occurs within the growth plate. We investigated paraffin
      embedded tissue sections of ten male mice with an antibody directed against the
      recombinant PTN. Immunostaining for PTN was positive within the cytoplasm and the
      pericellular matrix of osteoblasts which lined the longitudinal mineralized
      septae of the epiphyseal plate. Within the zone of hypertrophic chondrocytes,
      immunolabelling for PTN was positive in the pericellular matrix of hypertrophic
      chondrocytes and within the opened lacunae of the apoptotic hypertrophic
      chondrocytes. The resting zone and the proliferation zone were PTN negative. The
      results of our study suggest that the known angiogenetic peptide PTN plays a role
      in the process of angiogenesis in the growth plate.

PMID- 11510909
TI  - Effect of chemotherapeutic agents on distraction osteogenesis. An experimental
      investigation in rabbits.
AB  - Limb-salvage operations such as vascularised or non-vascularised osseous grafts
      and allograft and callus distraction methods have replaced amputations because of
      the increase in the life expectancy of patients with malignant tumours. In this
      study we aimed to evaluate the effects of chemotherapeutic agents on distraction
      osteogenesis. For this purpose, 23 rabbits randomly divided into two groups were
      included in the study. The experimental group and the control group consisted of
      12 rabbits and 11 rabbits, respectively. The experimental group were administered
      chemotherapeutic agents with the protocol identified in the osteogenic sarcoma
      regimen. All the subjects were corticotomised in the metaphyseal-diaphyseal
      region, and both groups underwent distraction with a circular ring fixator. X-ray
      films, bone scintigraphy and histopathological examination were performed three
      times during the study. No difference between the two groups was observed in
      radiological, scintigraphical and histopathological studies carried out before
      the distraction period and following the end of the distraction period. In this
      study, it was shown that the use of antineoplastic drugs has no significant
      negative effect on distraction osteogenesis applied for reconstruction in
      rabbits. We think that it can be an alternative treatment method in humans as
      well.

PMID- 11510910
TI  - Shoulder proprioception: a comparison between the shoulder joint in healthy and
      surgically repaired shoulders.
AB  - Proprioceptive mechanisms appear to play a role in stabilizing the glenohumeral
      joint and may serve as a means for interplay between the static stabilizers and
      the dynamic muscle restraints. The aim of this study was to investigate
      proprioception of the joint in healthy and surgically repaired shoulders.
      Shoulder proprioception was measured in 44 subjects who were assigned to two
      experimental groups: group 1, healthy subjects (n = 24); and group 2, patients
      who have undergone surgical reconstruction (n = 20). Joint position sense was
      measured with a Cybex NORM isokinetic dynamometer. The results revealed no
      significant differences in proprioception between the dominant and nondominant
      shoulders in group 1. No significant mean differences were revealed between the
      surgical and contralateral shoulder in group 2 under any test condition. These
      results imply that arm dominance in healthy individuals does not influence the
      proprioceptive sensibility and that reconstructive surgery appears to restore
      some of these proprioception characteristics.

PMID- 11510911
TI  - The contribution of vitamin C to healing of experimental fractures.
AB  - The benefits of various minerals and vitamins on fracture healing have been
      demonstrated in animal models. Vitamin C is an essential substance in fracture
      healing but has not been studied previously on an experimental basis. Sixteen
      rats were grouped randomly into control and vitamin C-supplemented groups. The
      right tibias of all rats were fractured by digital manipulation. One group
      received single high dose of vitamin C intramuscularly. On the 5th, 10th, 15th,
      and 20th days, two rats from each group were killed and the tibias examined under
      light microscopy. It was seen that the vitamin C-supplemented group went through
      the stages of fracture healing faster compared with the control group.

PMID- 11510912
TI  - Implantable cardioverter defibrillators for ventricular tachyarrhythmia: current
      status and technological evolution.

PMID- 11510913
TI  - Epidemiology of human immunodeficiency virus (HIV) infection in dialysis: recent
      insights.

PMID- 11510914
TI  - A controlled study of sorbent suspension dialysis in chronic liver disease and
      hepatic encephalopathy.
AB  - To investigate the role of extracorporeal detoxification in cirrhotic patients
      with advanced hepatic encephalopathy not responding to medical treatment, 20
      patients were randomized to receive six hours of additional sorbent dialysis or
      ongoing standardized medical treatment. Following treatment, the clinical stage
      of encephalopathy remained unchanged in both groups. Abnormal sensory evoked
      potentials improved following sorbent dialysis (N70 latency, 128 ms before versus
      110 ms after treatment, P<0,05; cervico-cranial transmission, 7.7 ms versus 6.8
      ms, P<0.01) indicating improvement in important aspects of cerebral function. In
      contrast, brain function remained unchanged following medical treatment (N70
      latency, 114 ms versus 113 ms; cervico-cranial transmission, 7.7 ms versus 7.2
      ms, P=NS, respectively). Serum benzodiazepine levels decreased significantly
      after sorbent dialysis but not after medical treatment. Biocompatibility of
      sorbent dialysis was limited and clinical complications occurred in a proportion
      of patients. In conclusion, a six-hour treatment with sorbent suspension dialysis
      did not ameliorate the clinical stage of HE but improved neurophysiologic
      function in cirrhotic patients who had not responded to conventional medical
      treatment.

PMID- 11510915
TI  - Cuffed-tunneled femoral catheter for long-term hemodialysis.
AB  - BACKGROUND: Hemodialysis access is a challenging problem in patients with
      exhausted dialysis access sites of their upper extremities. Femoral arterio
      venous polytetrafluoroethylene (PTFE) graft is often necessary. The safety and
      efficacy of cuffed tunneled catheters at the femoral site for long-term
      hemodialysis has not been extensively studied. METHODS: We inserted 14 cuffed
      tunneled femoral catheters in 11 hemodialysis patients with exhausted dialysis
      access sites of their upper extremities. Access survival and risk of infection
      were compared with the 11 femoral PTFE grafts in 10 patients of our center during
      the same period. The choice of dialysis access was determined by the individual
      nephrologist. Access survival was defined as the achievement of a blood flow rate
      of at least 180 ml/min. RESULTS: The median survival of tunneled femoral catheter
      and PTFE graft were 166 days and 560 days respectively (log-rank test, p = 0.33).
      Seven of the 14 tunneled femoral catheter remained in use 3 months after
      insertion. The incidence of catheter- or graft-related infection was 0.38 and
      0.23 episodes per 100 catheter/graft days for tunneled femoral catheters and PTFE
      graft respectively (p = 0.6). Five tunneled catheters and one PTFE graft had to
      be removed because of infection. Blood flow rates achieved were comparable
      between tunneled femoral catheter and PTFE graft. CONCLUSIONS: Our preliminary
      data suggest that the cuffed tunneled femoral catheter has reasonable access
      survival and an acceptable risk of infection. It may provide a safe and effective
      access for long-term hemodialysis patients with exhausted access in their upper
      extremities, especially high risk patients who are not suitable for femoral PTFE
      graft creation.

PMID- 11510916
TI  - Effect of low molecular weight heparin on bone metabolism and hyperlipidemia in
      patients on maintenance hemodialysis.
AB  - The effect of low molecular weight heparin (LMWH) on serum lipid profile in
      hemodialysis remains controversial and its effect on bone metabolism has not been
      studied. A crossover study was conducted in 40 patients on stable hemodialysis
      using unfractionated heparin (UFH) for more than 24 months. These patients were
      then treated with a LMWH (nadroparin-Ca) for 8 months during hemodialysis and
      subsequently switched back to UFH for 12 months. Serum lipid profile, biochemical
      markers for bone metabolism, and bone densitometry (BMD) were monitored at four
      month intervals while all medications remained unchanged. Cholesterol (TC),
      triglyceride (TG), low-density lipoprotein-cholesterol (LDL-C), lipoprotein(a)
      (Lp(a)), apolipoprotein B (Apo B) were raised in 35%, 29%, 12%, 24% and 24% of
      patients respectively. High-density lipoprotein-cholesterol (HDL-C) and
      apolipoprotein A1 (Apo A-1) were reduced in 47% and 9% of patients. Bone-specific
      alkaline phosphatase (BALP) and intact osteocalcin (OSC), both reflecting
      osteoblastic activity, were raised in 65% and 94% of patients. Tartrate-resistant
      acid phosphatase (TRACP) reflecting osteoclastic activity and parathyroid hormone
      (PTH) were elevated in 35% and 88% of patients. Following LMWH treatment, TC, Tg,
      Lp(a) and Apo B were reduced by 7%, 30%, 21% and 10% respectively (p<0.05 or
      <0.01) while Apo A-1 were raised by 7% (p<0.01). Simultaneously, TRACP was
      reduced by 13% (p<0.05). These biochemical changes were detected soon after 4
      months of LMWH administration. Although BMD values in our patients were lower
      than those of age-matched normal subjects, significant changes were not observed
      with LMWH treatment. After switching back to UFH for hemodialysis, these
      biochemical indices reverted to previous values during UFH treatment with a
      significant higher level in TC and Apo B while serum Apo A-1 remained elevated.
      Our study suggests LMWH may partially alleviate hyperlipidemia and, perhaps,
      osteoporosis associated with UFH administration in patients on maintenance
      hemodialysis.

PMID- 11510917
TI  - A hybrid (numerical-physical) model of the left ventricle.
AB  - Hydraulic models of the circulation are used to test mechanical devices and for
      training and research purposes; when compared to numerical models, however, they
      are not flexible enough and rather expensive. The solution proposed here is to
      merge the characteristics and the flexibility of numerical models with the
      functions of physical models. The result is a hybrid model with numerical and
      physical sections connected by an electro-hydraulic interface - which is to some
      extent the main problem since the numerical model can be easily changed or
      modified. The concept of hybrid model is applied to the representation of
      ventricular function by a variable elastance numerical model. This prototype is
      an open loop circuit and the physical section is built out of a reservoir
      (atrium) and a modified windkessel (arterial tree). The corresponding equations
      are solved numerically using the variables (atrial and arterial pressures) coming
      from the physical circuit. Ventricular output flow is the computed variable and
      is sent to a servo amplifier connected to a DC motor-gear pump system. The gear
      pump, behaving roughly as a flow source, is the interface to the physical
      circuit. Results obtained under different hemodynamic conditions demonstrate the
      behaviour of the ventricular model on the pressure-volume plane and the time
      course of output flow and arterial pressure.

PMID- 11510918
TI  - Design improvement of the jellyfish valve for long-term use in artificial hearts.
AB  - In a previous communication, we reported a leaflet fracture in a Jellyfish valve
      that was incorporated into a blood pump, after a 312-day animal implant duration.
      Subsequent finite element analysis revealed that the fracture location was
      consistent with an area of maximum strain concentration. Therefore, the aim of
      this study was to improve the durability in the light of these findings. Based on
      the engineering analysis results, a new valve seat having a concentric ring of
      0.5-mm width, located at a radius of 7.0 mm, was designed and fabricated.
      Accelerated fatigue tests, conducted under the conditions recommended by ISO
      5840, demonstrated that the durability of this new prototype was extended by a
      factor of 10, as compared to the original valve. Moreover, further finite element
      analysis indicated that the maximum equivalent elastic strain of the proposed new
      valve was reduced by 52.3% as compared to the original valve. Accordingly, it has
      been confirmed that the modified Jellyfish valve is suitable for use in long-term
      artificial hearts.

PMID- 11510919
TI  - Hydrodynamic characterisation of ventricular assist devices.
AB  - A new mock circulatory system (MCS) was designed to evaluate and characterise the
      hydraulic performance of ventricular assist devices (VADs). The MCS consists of a
      preload section and a multipurpose afterload section, with an adjustable
      compliance chamber (C) and peripheral resistor (Rp) as principal components. The
      MCS was connected to a pulse duplicator system for validation, simulating a wide
      range of afterload conditions. Both pressure and flow were measured, and the
      values of the different components calculated. The data perfectly fits a 4
      element electrical analogon (EA). The MCS was further used to assess the
      hydrodynamic characteristics of the Medos VAD as an example of a displacement
      pump. Data was measured for various MCS settings and at different pump rates,
      yielding device specific pump function graphs for water and pig blood. Our data
      demonstrate (i) flow sensitivity to preload and afterload and (ii) the effect of
      test fluid on hemodynamic performance.

PMID- 11510920
TI  - Arterial compliance is an independent factor predicting acute hemodynamic
      performance of intra-aortic balloon counterpulsation.
AB  - Data concerning the effect of arterial compliance (AC) on hemodynamics during
      intraaortic balloon counterpulsation (IABC) are lacking. This study examines the
      effect of AC on acute hemodynamics induced by IABC in 15 patients with post
      infarction cardiogenic shock. AC was estimated by aortic pulse wave analysis
      using the reflection time index (RTI). Measurements were obtained once per day
      during IABC. The % reduction in systolic aortic pressure (ASAP), end-diastolic
      aortic pressure (AEDAP) and the peak aortic diastolic augmentation (PADA) were
      used as performance indices of IABC; 107 sets of measurements were obtained.
      Multivariate analysis indicated an independent association of each IABC
      performance index with AC (p<0.05). A high AC group (RTI< or =20.6%, n=40) and a
      low AC group (RTI>20.6%, n=67) were obtained. DeltaSAP deltaEDAP and PADA were
      significantly higher in the low AC group by almost 75%, 54.6% and 11.3% (p<0.03),
      while arterial blood pressure did not significantly differ. Arterial compliance
      is an independent factor affecting hemodynamics during IABC. RTI values higher
      than 20.6% may predict a better acute hemodynamic response to IABC.

PMID- 11510921
TI  - Heparin coating of the extracorporeal circuit combined with leukocyte filtration
      reduces coagulation activity, blood loss and blood product substitution.
AB  - BACKGROUND: Cardiopulmonary bypass is associated with activation of the
      coagulation cascade. Occasionally, this results in postoperative hemorrhage and
      consequently the need for blood products associated with increasing costs and
      risk of infection. Contact activation of the intrinsic coagulation pathway, and
      damage to cellular blood components with the release of proteolytic substances
      from neutrophil granulocytes have been linked to these coagulation disorders.
      METHODS: Eighteen routine CABG-patients were randomly assigned to totally heparin
      coated circuits (Bioline coating) combined with leukocyte filtration in a double
      blind protocol (group I), 34 patients served as controls (group II). Leukocyte
      filters were activated before release of the aortic crossclamp. Coagulation
      activity, postoperative blood loss, and substitution with blood products were
      assessed. RESULTS: Blood loss in the first 24h after surgery was significantly
      lower with combined application of heparin coating and leukocyte filters (group
      I) vs. controls (group II) (526+/-78 ml vs. 786+/-88 ml; p<0.05). Thrombin
      formation represented by prothrombin fragments 1+2 was significantly lower in
      group I vs. group II after declamping of the aorta (2.1+/-0. 3 nmol/L vs. 4.0+/
      0.3 nmol/L; p<0. 05). Group I showed higher AT II plasma than group II (48.8+/
      3.2% vs. 41.5+/-1.77%; p<0.05). CONCLUSIONS: Leukocyte filtration during
      reperfusion in heparin coated cardiopulmonary bypass circuits is associated with
      lower coagulation activation, decreased blood loss and reduced transfusion of
      packed red cells in elective CABG patients.

PMID- 11510922
TI  - Somatosensory evoked potentials in patients affected by unilateral
      cerebrovascular lesions with onset during the perinatal period or adulthood.
AB  - Unilateral cerebrovascular lesions occurring during adulthood have been reported
      to be accompanied by high-amplitude somatosensory evoked potentials over the
      nonaffected hemisphere; however, the mechanisms by which somatosensory evoked
      potential amplitude increases over the nonaffected hemisphere are still unclear.
      To investigate the eventual presence of similar amplitude abnormalities in
      children, we recorded somatosensory evoked potentials in three groups of
      patients: one with unilateral cerebrovascular lesions that occurred during the
      perinatal period and another two with unilateral cerebrovascular lesions
      occurring during late adulthood or old age. Group 1 was comprised of 12 children
      and young adults (age range 2 3/12-31 years, 6 males and 6 females) who suffered
      from unilateral cerebrovascular lesion with perinatal onset. Four control groups
      were arranged with age matched to that of the patients. Adult patients were
      subdivided into two subgroups (group 2: n = 10, all males; group 3: n = 18, 12
      males and 6 females) on the basis of the presence or absence of sensory
      impairment over the hemiplegic side. In group 1, the four youngest subjects, aged
      less than 6 years, were found to show somatosensory evoked potentials of
      abnormally high amplitude over the nonaffected hemisphere, with a "giant" main
      negative wave at around 45 ms (range 38.7-49.2), strictly localized over the
      central areas contralateral to the lesion; in normal controls, there was no such
      wave. All patients in group 2 were found to be affected by large infarctions in
      the territory of the middle cerebral artery, whereas patients in group 3
      presented with subcortical lesions of the internal capsule isolated or in
      association with an involvement of the frontal and/or temporal cortex. Regarding
      somatosensory evoked potential parameters measured over the nonaffected
      hemisphere in adult/elderly subjects, a significant difference was observed for
      N20 and P22 latency, which was longer in both groups of patients than in
      controls. There is a significant difference in the neurophysiologic consequences
      of unilateral cerebrovascular lesion, as well as over the nonaffected hemisphere,
      if it occurs during early infancy or during adulthood. Our findings show a new
      type of "giant" somatosensory evoked potentials in some children affected by
      unilateral cerebrovascular lesion with perinatal onset.

PMID- 11510923
TI  - Antineuronal nuclei immunohistochemical staining patterns in childhood
      ependymomas.
AB  - NeuN, the mouse-derived monoclonal antibody to the reportedly neuron-specific
      nuclear protein, has been observed to react with many different types of normal,
      postmitotic neurons throughout the central and peripheral nervous systems. We
      retrospectively examined 23 surgical specimens (collected from 20 patients)
      originally diagnosed at our institution between 1983 and 1999 as ependymoma (9),
      myxopapillary ependymoma (1), anaplastic/malignant ependymoma (10), and primitive
      neuroectodermal tumor with ependymal differentiation (3). The ependymomas
      included lesions from the spine (3), cerebrum (5), and posterior fossa (15).
      Representative formalin-fixed, paraffin-embedded sections from each tumor were
      subjected to immunohistochemical staining with antibody against NeuN (Chemicon
      International, Inc, Temecula, CA). Five astrocytomas, four primitive
      neuroectodermal tumors, and normal cerebral cortex and ependyma from autopsy
      brains of premature newborns, term infants, and older children served as
      controls. Thirteen ependymal tumors had positive nuclear staining ranging from
      rare tumor cells to numerous groups of cells; of these, 9 were anaplastic
      ependymomas and had the most staining. These studies suggest that some
      ependymomas arise from a pluripotential neuroglial cell.

PMID- 11510924
TI  - Affective illness in children and adolescents: patterns of presentation in
      relation to pubertal maturation and family history.
AB  - Affective illness is now recognized as a common problem in all age groups, and
      the various patterns have been well documented in adults. The objective of this
      study was to evaluate the patterns of affective illness in children and determine
      changes with increasing age and family history. One hundred children/adolescents
      with affective illness (72 boys and 28 girls; age range 2-20 years; mean age 10
      years), who were consecutively referred to the Pediatric Behavioral Neurology
      Program, Children's Medical Center at Dallas, were evaluated for the pattern and
      course of affective illness symptoms, family history, and pubertal stage. Seven
      patterns of affective illness were identified. In the 65 prepubertal children
      (Tanner stage 1), disorders with hypomanic/manic symptomatology were most common
      (47/65, 72%): mania (2/65, 3%), hypomania (8/65, 12%), cyclothymia (11/65, 17%),
      juvenile rapid-cycling bipolar disorder/ultradian cycling bipolar disorder (8/65,
      12%), and dysthymia with bipolar features (18/65, 28%). In contrast, the 26 fully
      pubertal adolescents (Tanner stages 3-5) had a predominance of patterns with only
      depressive symptomatology (16/26, 61%): dysthymia (4/26, 15%) and depression
      (12/26, 46%), along with juvenile rapid-cycling bipolar disorder/ultradian
      cycling bipolar disorder (6/26, 23%). Affective illness, alcoholism, and drug
      abuse were prominent in the family histories, regardless of the child's pattern
      of symptoms. Family histories of character disorder and Briquet's syndrome were
      also common, but thought disorder, suicide, and homicide were infrequent. This
      study supports the clinical observation that the presentation of affective
      illness changes with age: manic features predominate in younger children, whereas
      depressive symptomatology is more evident with pubertal maturation.

PMID- 11510925
TI  - Absence of hippocampal sclerosis in children with multiple daily seizures since
      infancy.
AB  - We report a series of nine children with multiple daily seizures since infancy
      who underwent functional hemispherectomy that included en bloc resection of the
      hippocampus and the temporal neocortex. In all cases, the hippocampi were normal
      by conventional histology despite the fact that these patients had suffered from
      recurrent seizures over a long period of time. This observation suggests that
      extremely frequent seizures in childhood are not invariably associated with the
      development of hippocampal sclerosis.

PMID- 11510926
TI  - Should children with Bell's palsy be treated with corticosteroids? A systematic
      review.
AB  - The objective of this study was to evaluate the effect of corticosteroids in the
      treatment of pediatric Bell's palsy. A systematic review of trials that included
      pediatric (< 16 years old) cases with Bell's palsy and involved the use of
      steroids was conducted. Eight trials were identified, five of which were
      randomized, and prednisone was used in six trials, whereas corticotropin was used
      in the other two. The methods of randomization and allocation concealment of the
      treatments used were rarely reported. Only one trial was done exclusively in
      children; none of the other seven trials analyzed the pediatric cases separately.
      Four trials reported some benefit from steroids. The pediatric trial did not
      provide evidence for benefit from corticosteroids. There was substantial
      heterogeneity in the population and interventions used; hence a meta-analysis was
      not done. Based on this systematic review, we do not recommend the routine use of
      steroids in children with Bell's palsy.

PMID- 11510927
TI  - Video-assisted thoracoscopic thymectomy in juvenile myasthenia gravis.
AB  - As video-assisted thoracoscopic surgery for thymectomy has been reported to be as
      effective as traditional open surgical approaches in predominantly adult patients
      with myasthenia gravis, we applied this procedure to juvenile patients with this
      condition. Six patients underwent total thymectomy using the video-assisted
      technique (1997-98). Six patients in whom a median transsternal approach was used
      (1989-95) formed the comparison group. The two patient groups were similar in
      terms of age at thymectomy and preoperative clinical severity. There were no
      serious perioperative complications in either group. Minimum post-thymectomy
      duration of follow-up in the video-assisted thoracoscopic surgery patients was
      2.3 years (mean 2.7 years), with all patients clinically improved over their
      baseline status. Preliminary results suggest that video-assisted thymectomies are
      comparably effective to transsternal procedures in treating generalized juvenile
      myasthenia gravis and can be safely performed in children as young as 20 months
      of age. In addition, video-assisted surgeries are less invasive than transsternal
      approaches, significantly shorten the postoperative hospital stay, and have
      superior cosmetic results.

PMID- 11510928
TI  - Cerebral venous thrombosis in children.
AB  - Cerebral venous thrombosis is an important cause of stroke in children.
      Understanding the natural history of the disease is essential for rational
      application of new interventions. We retrospectively identified 31 children with
      cerebral venous thrombosis confirmed by head computed tomography (4 patients) or
      by magnetic resonance imaging (27 patients). Risk factors, clinical and
      radiographic features, and neurologic outcomes were analyzed. There were 21 males
      and 10 females aged 1 day to 13 years (median 14 days). Nineteen (61%) were
      neonates. The most common risk factors included mastoiditis, persistent pulmonary
      hypertension, cardiac malformation, and dehydration. The chief clinical features
      were seizures, fever, respiratory distress, and lethargy. Fifteen patients had
      infarctions (8 hemorrhagic, 7 ischemic). Protein C and antithrombin III
      deficiency were the most common coagulopathies among 14 tested patients. On
      discharge, 11 patients were normal, 17 had residual deficits, and 2 patients
      died. Twenty-seven patients were followed from 1 month to 12 years (mean 22
      months). At follow-up, 11 patients were normal, and 13 patients had development
      delay. One had residual hemiparesis and cortical visual impairment. Two had other
      deficits. Neonatal cerebral venous thrombosis is probably more common than
      previously thought, and outcomes are worse in this group. All children with
      cerebral venous thrombosis should be tested for coagulation disorders.

PMID- 11510929
TI  - Melatonin for treatment of sleep disorders in children with developmental
      disabilities.
AB  - This study explored the safety and efficacy of synthetic melatonin in the
      treatment of sleep problems in 20 children with developmental disabilities, in a
      randomized, double-blind, placebo-controlled 6-week trial of melatonin versus
      placebo. All but 2 children fell asleep more quickly when receiving melatonin
      than placebo. Overall, the greater the sleep latency (time to fall asleep) was at
      baseline or when receiving placebo, the more pronounced was the decrease in sleep
      latency with melatonin. The effect of melatonin on sleep latency was significant
      (P < .05). The duration of sleep while receiving melatonin was significantly
      greater than baseline (P < .007) but was not significantly different from
      placebo, and no difference in the number of awakenings was noted. No side effects
      were reported. Eleven of 18 parents (61%) correctly identified the weeks their
      child received melatonin. This study suggests that synthetic melatonin reduces
      sleep latency in children with developmental disabilities.

PMID- 11510930
TI  - Temporal lobectomy in early childhood: the need for long-term follow-up.
AB  - We retrospectively identified 15 children ages 12 years and under with
      anticonvulsant resistant epilepsy who underwent a temporal lobectomy at
      Children's Hospital, Boston, between 1978 and 1993. Our aim was to study the long
      term seizure outcome. Data pertaining to preoperative evaluation,
      electroencephalography (EEG), neuroimaging, surgery, seizure outcome, and
      postoperative complications were reviewed. Only patients followed for more than
      12 months were included. The average duration of follow-up was 57 months. At the
      last visit, 47% (7 of 15) of the children were seizure free or only had auras:
      another 33% (5 of 15) had > 90% reduction in seizure frequency. Three patients
      had < 90% seizure reduction. Four cases were initially seizure free but had
      subsequent recurrence between 11 and 28 months after the epilepsy surgery.
      Factors associated with a good outcome include exclusively focal EEG discharges
      or an imaging suggestive of a low-grade tumor; factors associated with a poor
      outcome include generalized EEG discharges and a normal magnetic resonance image.
      Temporal lobectomy is useful in the treatment of early childhood drug-resistant
      partial epilepsy, but long-term follow-up is necessary as late seizure recurrence
      may occur up to 28 months after surgery.

PMID- 11510931
TI  - Prognostic significance of hyperechogenic lesions in the basal ganglia and
      thalamus in neonates.
AB  - Neonatal cranial ultrasonography at times reveals hyperechogenic lesions in the
      basal ganglia and thalamus. These lesions have been attributed to a wide variety
      of pathologic states, among them toxoplasmosis, rubella, cytomegalovirus, and
      herpes simplex (TORCH) infections, chromosomal abnormalities, and asphyxia. The
      clinical significance in terms of the neurodevelopmental outcome of this
      radiologic abnormality is unknown. We performed a developmental evaluation on 16
      children aged 2 to 6 years in whom neonatal cranial ultrasonography had
      demonstrated hyperechogenic lesions in the basal ganglia or thalamus and had no
      other neurodevelopmental risk factors. There was no significant difference
      between the average Developmental Quotient of the target population and the
      normal population in regard to developmental status. We conclude that in our
      population, an isolated finding of hyperechogenic lesions in the basal ganglia is
      probably not a predictor of poor neurodevelopmental outcome.

PMID- 11510932
TI  - Congenital varicella syndrome: case with isolated brain damage.
AB  - We report a case of congenital varicella syndrome after maternal infection during
      the 10th week of pregnancy. None of the typical abnormalities were manifested at
      birth; however, the child experienced neonatal tonic convulsions that evolved to
      refractory focal epilepsy with adversive, complex partial, and secondarily
      generalized seizures. At the age of 5 years, after a prolonged generalized
      seizure following cranial trauma, cranial computed tomography (CT) was performed.
      It led to the misdiagnosis of post-traumatic intracerebral hemorrhage.
      Afterwards, because of persistent seizures and developmental delay with mild or
      slight intellectual deficit, the next CT and magnetic resonance imaging (MRI)
      investigation at 8 years of age disclosed massive malformation of the left
      cerebral hemisphere. The serologic evidence of varicella-zoster virus-specific
      IgG antibodies without a history of varicella disease after birth and maternal
      infection during early pregnancy were crucial to diagnosing the rare syndrome of
      congenital varicella consisting of isolated brain damage.

PMID- 11510933
TI  - Medullomyoblastoma: case report.
AB  - This 7-year-old boy presented with a 2-week history of headache, nausea,
      vomiting, anorexia, lethargy, and unsteadiness of gait. Brain magnetic resonance
      imaging (MRI) revealed a cystic mass within the vermis of the cerebellum. A
      suboccipital craniectomy was performed to remove a tumor that contained primitive
      neuroectodermal cells with florid skeletal muscle differentiation.
      Immunohistochemical studies and electron microscopy confirmed the presence of
      both a primitive neuroectodermal component and rhabdomyoblastic differentiation,
      consistent with the diagnosis of medullomyoblastoma. This exceedingly rare tumor
      of the cerebellar vermis of children is characterized by two components:
      primitive neuroectodermal tumor cells and skeletal muscle. Although the
      histogenesis remains uncertain, advances in immunohistochemistry and electron
      microscopy suggest the origin of this tumor from a multipotential stem cell
      precursor.

PMID- 11510934
TI  - Acetazolamide treatment for infantile central sleep apnea.
AB  - Central sleep apnea is a common respiratory pattern in healthy neonates.
      Nevertheless, frequent central sleep apnea associated with drops in oxygen
      saturation may contribute to infantile morbidity. Recently, low-dose
      acetazolamide was shown to reduce symptomatic central sleep apnea in adults. We
      treated 12 infants, median conceptional age 42 weeks (range, 40-44 weeks), with
      central sleep apnea. In all cases, the central apnea index was >40/h total
      sleeping time (apnea > or = 3 sec). The cumulative duration of drops in oxygen
      saturation below 90% was more than 3 min/h total sleeping time. All individuals
      received acetazolamide 7 mg/kg/day (orally, divided in three doses) for 11 weeks.
      Polysomnography was begun 10 hours before the first dose and continued for 10
      hours after the third dose. Polysomnography was repeated after 6 weeks of
      treatment and 1 week after acetazolamide therapy was discontinued. Comparison of
      the respiratory patterns before and after treatment (10-hour recording after the
      third dose) showed a decrease in the median central apnea index from 74/h (range,
      42-152/h) to 13/h (range, 6-49/h). The median of the cumulative duration of drops
      in oxygen saturation below 90% decreased from 3.6 min/h (range, 3.1-9.2 min/h) to
      0.07 min/h (range, 0-0.5 min/h). Basal oxygen saturation increased from 95 (92
      97%) to 98% (96-99%). This improvement was maintained in the final
      polysomnography (12 weeks after therapy was begun and 1 week after completion of
      the 11-week course). No adverse effects were noted. We conclude that low-dose
      acetazolamide treatment may be useful for the treatment of central infantile
      sleep apnea associated with hypoxemia.

PMID- 11510935
TI  - Changes in the antioxidant system in epileptic children receiving antiepileptic
      drugs: two-year prospective studies.
AB  - The aim of this study was to measure changes in the antioxidant systems of
      epileptic children who had been receiving either valproate or carbamazepine
      monotherapy for 2 years. For this purpose, levels of erythrocyte glutathione,
      glutathione peroxidase, superoxide dismutase, and serum lipid peroxidation in 25
      healthy children and 27 children who had previously been diagnosed as having
      epilepsy but who had not, prior to the study, received antiepileptic drugs were
      tested. Of the 27 epileptic children, 14 were given valproate, and the remaining
      13 were given carbamazepine; these tests were repeated in the 13th and 24th
      months of treatment. The results showed that, during valproate therapy, the lipid
      peroxidation levels of the epileptic children increased and the glutathione
      peroxidase levels decreased in comparison with those levels recorded in the
      control and pretreatment groups. In addition, the superoxide dismutase levels
      were found to be increased during the first year of valproate therapy when
      compared with those of the pretreatment group. However, during carbamazepine
      therapy, lipid peroxidation levels increased when compared with the control group
      only, not the pretreatment group. Furthermore, the results showed that during the
      second year of treatment, the superoxide dismutase levels of the children
      receiving carbamazapine monotherapy were found to be higher than those of both
      the control and pretreatment groups. From these results, it can be concluded that
      the antioxidant systems of the children who had been receiving valproate therapy
      during the 2 years were more significantly affected than those of the children
      who had been receiving carbamazepine.

PMID- 11510936
TI  - Neurofibromatosis type 1 presenting with hand dystonia.
AB  - Neurofibromatosis type 1 is frequently associated with increased intensity T2
      weighted magnetic resonance imaging (MRI) brain abnormalities, called
      "unidentified bright objects." Unidentified bright objects are generally held to
      be benign and tend to decrease in size during adulthood. We describe a case of
      neurofibromatosis type 1 with a similar thalamic and subthalamic MRI abnormality
      associated with contralateral hand dystonia. Over a 2-year follow-up, the lesions
      showed a reduction in size apparently correlated with a reduction in symptoms.

PMID- 11510937
TI  - Leigh disease: clinical, neuroradiologic, and biochemical study of three new
      cases with cytochrome c oxidase deficiency.
AB  - Three cases of Leigh disease are described. In all three, symptoms began in the
      first months of life, with muscle hypotonia, lactic acidosis, and psychomotor
      delay. The diagnosis was made on the basis of the clinical characteristics,
      biochemical abnormalities, and typical brain magnetic resonance imaging with
      symmetric lesions suggesting bilateral necrosis at the level of the basal ganglia
      and of the midbrain. Cytochrome c oxidase (complex IV of the mitochondrial
      respiratory chain) deficiency was demonstrated in muscle tissue in all patients
      and confirmed in skin fibroblasts in patient 3. A genetic heterogeneity was
      present in these patients since only one had a SURF-1 gene mutation. The
      clinical, biochemical, and neuroradiologic aspects are discussed. Finally, the
      finding of facial dysmorphisms in the cytochrome c oxidase deficiency observed in
      one of the described cases is of extreme interest; to our knowledge, this
      association has never been reported in the literature.

PMID- 11510938
TI  - Cavernous angioma of the brain stem simulating diffuse pontine glioma.
AB  - Brainstem vascular malformations can sometimes simulate other conditions such as
      multiple sclerosis and pontine glioma. We report a case of brainstem cavernous
      angioma for which clinical course and radiologic appearance were suggestive of a
      pontine glioma. The diagnosis was uncertain until the clinical and radiologic
      evolution made it clear that the patient had a cavernous angioma. We suggest that
      brainstem angioma be considered as a differential diagnosis for pontine glioma.

PMID- 11510939
TI  - Cytochrome c oxidase partial deficiency-associated Leigh disease presenting as an
      extrapyramidal syndrome.
AB  - Leigh disease is a subacute neurodegenerative disorder characterized by symmetric
      necrotic lesions in the basal ganglia, cerebellum, thalamus, brain stem, and
      optical nerves and caused by altered oxidative phosphorylation. We describe the
      clinical, biochemical, neuroimaging, and molecular studies of a 19-year-old boy
      with early-onset Leigh disease manifesting as severe extrapyramidal disorder with
      generalized dystonia and choreoathetosis. He was born of healthy parents after an
      uneventful pregnancy and delivery. At the age of 2 1/2 years, after a minor
      respiratory infection, he developed unstable, broad-based gait and tremor of the
      hands. These symptoms persisted for the next several years, when ataxia became
      more prominent. Difficulty in swallowing, dysarthria, trunk dystonia, and marked
      dyskinesia of the arms and hands gradually developed. Nystagmus, transient
      ptosis, and strabismus also appeared. Abnormal laboratory findings included
      elevated plasma and cerebrospinal fluid lactate and pyruvate, with an abnormal
      lactate/pyruvate ratio. Cranial computed tomography and magnetic resonance
      imaging demonstrated signs of cerebellar atrophy, bilateral and symmetric
      hypodensities in the lentiform nucleus and thalamus, and transient
      hyperintensities of cerebral peduncles in T2-weighted sequences suggestive of
      Leigh disease. Muscle biopsy revealed isolated fiber atrophy, necrotic fibers
      undergoing phagocytosis, and no ragged-red fibers. The measured catalytic
      activity of cytochrome c oxidase in skeletal muscle homogenates demonstrated a
      partial cytochrome c oxidase deficiency No abnormalities in the mitochondrial
      genome and in the SURF-1 gene were found. The boy is currently receiving levodopa
      therapy, creatine monohydrate, and a high dosage of thiamine and lipoic acid, his
      condition is stabilized, and extrapyramidal symptoms are less pronounced.

PMID- 11510940
TI  - Neonate with spinal hypoplasia on T12 and a localized vertebral malformation on
      L4.
AB  - We report a case of a neonate with sectional narrowing of the spinal cord on the
      level of T12 to L2 and a deformed vertebral body on a different level, L4. In
      previously described cases of sectional spinal dysgenesis, the vertebral and
      spinal cord malformations are usually found on the same level. Our case may
      represent a new variant of spinal dysgenesis.

PMID- 11510941
TI  - Is hyperprolinemia type I actually a benign trait? Report of a case with severe
      neurologic involvement and vigabatrin intolerance.
AB  - Hyperprolinemia type I is a deficiency of proline oxidase (McKusick 23950),
      leading to hyperprolinemia and iminoglycinuria, usually with renal involvement.
      Hyperprolinemia type I is considered a benign trait. We reported a case of
      hyperprolinemia type I with a severe neurologic disorder and without renal
      involvement. The patient had marked psychomotor delay and right hemiparesis.
      Epilepsy was characterized by status epilepticus or a cluster of seizures.
      Laboratory findings revealed elevated levels of proline in the serum, urine, and
      cerebrospinal fluid without delta1-pyrroline 5-carboxylate dehydrogenase in the
      plasma or urine. Fluorescence in situ hybridization excluded a chromosome 22q11
      deletion. Vigabatrin inhibits ornithine transaminase. Thus, vigabatrin could lead
      to a depletion of the normal pool of pyrroline 5-carboxylate dehydrogenase and
      could aggravate the clinical condition of the child. In this study, vigabatrin
      was discontinued. In the following months, the patient had marked psychomotor
      improvement, without modification of the epilepsy. We suggest that vigabatrin
      should be avoided in hyperprolinemia type I.

PMID- 11510942
TI  - Idiopathic trigeminal sensory neuropathy in childhood.
AB  - Harris first reported transient idiopathic trigeminal sensory neuropathy in 1935,
      although it later appeared that, in some of his patients, this condition evolved
      to typical chronic and painful trigeminal neuralgia. The patients who were later
      described by Hill and Hughes suffered a combined motor-sensory Vth cranial nerve
      dysfunction, and most cases reported by Spillane and Wells developed sustained
      permanent trigeminal neuropathy. The largest reported series of pure trigeminal
      sensory neuropathy includes 10 adults with varying degrees of sensory disturbance
      confined to all three nerve divisions. These patients experienced no facial pain
      or motor deficit, and 5 (50%) recovered completely within a few months. It is
      estimated that typical trigeminal neuralgia occurs in about 1 in 25,000 of the
      population and is uncommon prior to the third decade, with 1% of the cases
      occurring before the age of 20 years. To our knowledge, we present the first
      clinical report of idiopathic trigeminal sensory neuropathy occurring in
      childhood.

PMID- 11510943
TI  - Continuous-display four-channel electroencephalographic monitoring in the
      evaluation of neonates with paroxysmal motor events.
AB  - The objective of this study was to determine the value of continuous-display four
      channel electroencephalographic (EEG) monitoring to distinguish epileptic front
      nonepileptic paroxysmal motor events. Five full-term neonates with paroxysmal
      motor events were included in the study. Nurses were instructed to print
      contiguous pages of the continuous-display four-channel EEG monitoring and to
      activate the event marker on the simultaneously conducted continuous video-EEG
      telemetry unit during each paroxysmal motor event. The printouts from the
      continuous-display four-channel EEG monitoring were interpreted and compared with
      the corresponding segments of continuous video-EEG telemetry. Thirty paroxysmal
      motor events were captured. Sixteen paroxysmal motor events were epileptic, and
      14 were nonepileptic. The interpretation of the printouts of the continuous four
      channel EEG monitoring concurred with an independent interpretation of the
      corresponding video-EEG telemetry segments in all of the events. Continuous
      display four-channel EEG monitoring is a valuable tool in the evaluation of
      neonates with paroxysmal motor events since it reliably distinguishes epileptic
      and nonepileptic events.

PMID- 11510944
TI  - Benign parasomnias and nocturnal frontal epilepsy: differential diagnosis in a
      case report.
AB  - We report the case of a 13-year-old boy who complained of complex motor episodes
      during sleep characterized by sudden arousal followed by deambulation associated
      with automatic movements and vocalization. His family history included both
      epileptic and psychiatric disorders. The patient himself presented
      psychopathologic traits and adaptive difficulties. In support of an epileptic
      origin of these phenomena were the stereotyped fashion in which they appeared and
      their responsiveness to carbamazepine. We classified the present case as a
      nocturnal frontal epilepsy with variable manifestations that can be classified as
      paroxysmal arousals, paroxysmal dystonia, and epileptic nocturnal wanderings. It
      was possible to differentiate such events from the most common parasomnias on the
      basis of videopolysomnographic studies.

PMID- 11510945
TI  - Kinetics and inductive potency of 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin
      (H7CDD) in rats.
AB  - The kinetic properties and the inductive potency of 1,2,3,4,6,7,8
      heptachlorodibenzo-p-dioxin (H7CDD) were studied in Wistar rats following
      subcutaneous (s.c.) injections. For assessing the dose-response, rats were
      treated with a single dose of 3. 10 or 30 microg H7CDD/kg body wt. Tissue
      concentrations and enzyme induction were measured 1, 2, and 3 weeks after
      treatment, and in the 30 microg/kg group additionally after 6, 20 and 57 weeks.
      Tissue concentrations increased dose-dependently from 3 to 30 microg/kg.
      Concentrations in liver were always higher than in adipose tissue, the
      concentration ratio: liver/adipose tissue varied between 32 and 67. The activity
      of (ethoxyresorufin O-deethylase) (EROD) in liver microsomes was clearly induced
      by H7CDD, reaching maximal induction three weeks after treatment. (3-fold at 3
      microg/kg, 5-fold at 10 microg/kg and nearly 30-fold at 30 microg/kg). For
      assessing the time dependency, tissue levels and hepatic enzyme induction were
      monitored over a period of 57 weeks after a single s.c.-injection of 30 microg
      H7CDD/kg body wt. Hepatic concentrations of the congener remained rather constant
      from the 2nd to the 20th week after treatment (280 ng/g and 319 ng/g,
      respectively). In contrast, concentrations in adipose tissue and thymus increased
      2-fold during this period, and 20 weeks after injection reached a maximum of 11
      ng/g and 3 ng/g, respectively. Thereafter, the concentrations decreased and
      tissue levels of 91 ng/g (liver), 3 ng/g (adipose tissue) and 2 ng/g (thymus)
      were detected 57 weeks after treatment. The elimination half-life (t 1/2)
      calculated from our data was 140 days in liver and 130 days in adipose tissue.
      The reasonable explanation for the increase in tissue concentrations of H7CDD up
      to 20 weeks after treatment is the slow release of this congener from the
      subcutaneous injection site. Induction of hepatic EROD activity always closely
      followed changes in the hepatic concentrations of H7CDD, reaching a maximum 3
      weeks after treatment and remaining at this level until the 20th week.
      Correlation analysis of hepatic H7CDD concentrations versus the extent of EROD
      induction indicated a linear relationship in a double-logarithmic plot. When
      compared with TCDD, the hepatic monooxygenase-inducing potency of H7CDD within
      the low dose range was found in the rat to be 170 to 440-times lower than that of
      TCDD. Measurement of 14C-caffeine demethylation, using a 14CO2 breath test,
      revealed a similar time course in vivo when compared with the microsomal EROD
      activity ex vivo.

PMID- 11510946
TI  - Intracellular third loops in AT1 and AT2 receptors determine subtype specificity.
AB  - The recently cloned angiotensin II type 2 (AT2) receptor is a member of the seven
      transmembrane G-protein coupled receptor superfamily with a relatively low
      sequence homology with the angiotensin II type 1 (AT1) receptor subtype and
      counteracts the growth action of AT1 receptor. Intracellular third loops are
      known to be involved in interactions with various G proteins. We hypothesized
      that the intracellular third loop plays critical roles in determining the
      specificity of opposite functions of AT1 and AT2 receptor subtypes and examined
      this possibility using chimeric AT1 receptor, of which intracellular third loop
      is replaced with that of AT2 receptor. We transfected this chimeric receptor into
      PC 12 cells and observed that stimulation of this receptor inhibited
      extracellular signal-regulated kinase (ERK) activation and induces apoptosis,
      whereas the binding characteristics of this receptor remained those of ATI
      receptor. Taken together, these results support the notion that intracellular
      third loop is the critical determinant for mutually antagonistic AT1 and AT2
      receptors' signaling pathways.

PMID- 11510947
TI  - Short-chain fatty acids enhance diffusional ca transport in the epithelium of the
      rat cecum and colon.
AB  - We examined the effect of short-chain fatty acids (SCFAs) on Ca absorption from
      the large intestine in rats in vitro. An Ussing-type chamber technique was used
      to determine the net transport of Ca from the luminal side to the basolateral
      side of isolated epithelium in cecum and colon preparations. The concentration of
      Ca in the serosal and mucosal Tris buffer solution was 1.25 mM and 10 mM,
      respectively. Both solutions were warmed at 37 degrees C and bubbled with 95% O2
      and 5% CO2. During and after the incubation period (30 min or 60 min), the Ca
      concentration in the serosal medium was determined and the net transepithelial Ca
      transport was evaluated. The addition of 80 mM acetic acid, 40 mM propionic acid
      and 10 mM butyric acid to the mucosal medium increased net Ca absorption (about
      300%) in the cecum and colon. An individual application of acetic, propionic or
      butyric acid (0.01 to 100 mM) to the mucosal medium also increased net Ca
      absorption at doses of 10 mM and /or 100 mM in the cecum and colon. An increase
      in solute concentration in the mucosal medium by addition of glycerol or PGE400,
      or a decrease in pH (7.0-3.0) by addition of HCl did not affect transepithelial
      Ca transport. We concluded that SCFAs affect the epithelial tissue and promote Ca
      absorption from the large intestine in vitro. The enhancement of Ca transport
      induced by SCFAs might be involved in the paracellular transport mechanism.

PMID- 11510948
TI  - Diabetes related cardiomyopathy time dependent echocardiographic evaluation in an
      experimental rat model.
AB  - Type I diabetes is associated with a unique form of cardiomyopathy in the absence
      of atherosclerosis. The mechanisms involved in this phenomenon are not defined,
      but in humans this is associated with initial diastolic dysfunction followed by
      altered contractile performance. A relevant animal model would provide
      opportunities for mechanistic studies and experimental therapeutics, but none
      have been previously established for this unique form of cardiac pathophysiology,
      particularly with respect to clinically relevant and time-dependent diastolic and
      systolic assessments. Here we tested the hypothesis that the streptozotocin rat
      model mimics human phenomena with respect to time-dependent diastolic and
      systolic performance deficits, and investigated a role for cardiac hypertrophy
      and/or fibrosis. Streptozotocin was dosed 65 mg/kg i.p. and cardiac performance
      was assessed longitudinally for 56 days using noninvasive echocardiographic
      techniques. Significant hyperglycemia was detected within 3 days and remained
      elevated throughout the study (p<0.05). Significant reductions in HR and
      diastolic performance (transmitral flow velocities and slopes) were observed
      within 3 days relative to age matched controls, and these reductions progressed
      throughout the 56 day study. In contrast, statistically significant systolic
      dysfunction (LV fractional shortening, cardiac output) and LV dilation were
      detected only after 35 days. Increases in LV size and/or extent of fibrosis were
      not observed at any time. These results demonstrate the value of
      echocardiographic methods for time-dependent diastolic and systolic assessments
      in rodent models. Furthermore, diastolic dysfunction precedes contractile
      abnormalities in the streptozotocin model, similar to events that occur in
      humans.

PMID- 11510949
TI  - Presence of melatonin in the human hepatobiliary-gastrointestinal tract.
AB  - A variety of speculations about the possible origin and physiological role of the
      neurohormone melatonin in the gastrointestinal tract exist. However, the
      experimental evidence supporting any of these theories is not substantial and are
      missing for humans. We studied the distribution of melatonin which was measured
      with radioimmunoassay in the following compartments and organs of the human
      hepatobiliary-gastrointestinal tract: bile (obtained by endoscopic retrograde
      cholangiopancreaticography), peripheral venous and portal venous blood (obtained
      from patients undergoing liver transplantation), endoscopically derived biopsies
      (mainly consisting of mucosa and submucosa) of stomach, duodenum, large intestine
      as well as in resected liver tissue. Melatonin concentrations in gastrointestinal
      mucosa were between 136 +/- 27 pg/100 mg (stomach) and 243 +/- 37 pg/100 mg
      (descending colon, each n = 5). Biliary melatonin concentrations (85 +/- 45
      pg/ml) correlated well with plasma concentrations (55 +/- 38 pg/ml, each n = 14)
      and a considerable amount of melatonin (about 51 ng/24 hours) appears to be
      excreted into the gut via the bile duct. Melatonin concentrations were slightly
      higher in portal than in peripheral venous blood and also the liver contained
      higher concentrations of melatonin than the blood. In conclusion the presence and
      distribution of melatonin in human gut, bile, liver and portal blood and the
      various reports on modulatory actions of melatonin on gut and liver functions
      suggest that melatonin may act as a mediator of inter-organ communication between
      gut and liver.

PMID- 11510950
TI  - Szygium aromaticum (L.) Merr. Et Perry (Myrtaceae) flower bud induces apoptosis
      of p815 mastocytoma cell line.
AB  - This study was conducted to investigate SAFB-induced apoptosis of mast cells as
      it pertains to both its basic drug mechanism and the potential therapeutics of
      the pathologic conditions accompanying mast cell proliferation. SAFB induced many
      apoptotic manifestations as evidenced by changes in cell morphology, generation
      of DNA fragmentation, activation of caspase 3, and DNA hypoploidy. The reduction
      of mitochondrial membrane potential and the release of cytochrome c to cytosol
      were also demonstrated. However, reduction of mitochondrial membrane potential
      and cytochrome c release were not prevented by caspase inhibitor zVAD-fmk or PTP
      blockers such as bongkrekic acid and cyclosporin A. Expression levels of Bcl-2
      and Fas remained unchanged following SAFB treatment. This results suggest that
      the clinical effect of SAFB may depend on the pharmacological mechanism
      regulating the demise of mast cells.

PMID- 11510951
TI  - Proinflammatory role of leptin in experimental colitis in rats benefit of
      cholecystokinin-B antagonist and beta3-agonist.
AB  - Leptin, a hormone primarily secreted from adipocytes, plays a key role in
      controlling body weight homeostasis. In vitro studies indicate that it is also
      implicated in immune responses. Hyperleptinaemia has been reported in acute
      inflammation, especially during the early stages of intestinal inflammation in
      rats. The present study investigated the possible role of leptin in the
      pathogenesis of trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats.
      Since no specific antagonist of leptin is available, a CCK-B antagonist (YM022)
      and a beta3 agonist (BRL37344) were used in this study to inhibit leptin
      secretion. Colitis was induced by intracolonic instillation of TNBS in rats. Five
      TNBS-groups were subcutaneously implanted with micropumps containing: placebo,
      YM022, BRL37344, BRL37344 and exogenous leptin simultaneously, or leptin alone.
      At sacrifices, colitis severity was assessed by macroscopic and histological
      scoring systems and by determination of tissue myeloperoxidase activity. The TNBS
      induced hyperleptinaemia was significantly reduced by YM022 and BRL37344
      (p<0.05). Inhibition of leptin secretion markedly reduced colonic inflammation,
      whatever the criteria considered (i.e. macroscopic, histological or biochemical).
      In contrast, administration of exogenous leptin completely abolished the
      beneficial effect of leptin-lowering drugs on colitis severity. These results
      provide the first direct evidence for an important deleterious role of leptin in
      the pathogenesis of experimental intestinal inflammation and suggest that a pro
      inflammatory activity is attributable to leptin in vivo. Further studies are
      required to determine if these results have clinical significance.

PMID- 11510952
TI  - Effects of endomorphin-2 on arterial blood pressure and pain threshold in
      spontaneously hypertensive rats and modification of these effects by beta
      funaltrexamine and nor-binaltorphimine.
AB  - The effects of intracerebroventricular (icv) administration of endomorphin-2 (E2)
      on arterial blood pressure and pain threshold in spontaneously hypertensive rats
      (SHR) and modification of these effects by K [OP2] and mu [OP3] opioid receptors
      antagonists were investigated. Endomorphin-2 administrated icv in doses of 8, 16
      and 32 mcg produced dose-dependent analgesic and hypotensive effect. In SHR
      decrease in blood pressure amounted 2.667, 4.0 and 6.534 kPa, respectively. Pain
      threshold increased by 1.7, 3.6 and 8.9 (g x 10). In Wistar Kyoto (WKY) strain,
      being the normotensive controls, E2 in doses of 8 and 16 mcg decrease in blood
      pressure was less pronounced and amounted 1.200 and 1.467 kPa, respectively,
      whereas the pain threshold increased by 7.2 and 10.4 (g x 10), respectively. Both
      E2 effects were antagonized by equimolar icv doses of beta-funaltrexamine (beta
      FNA). Equimolar doses of nor-binaltorphimine (nor-BNI) attenuated analgesic
      action of E2, but were without hypotensive action produced by E2. A strong
      correlation between drop in blood pressure and increase in pain threshold
      observed in the SHR and WKY strains after icv administration of E2, indicate
      close interaction between systems responsible for pain perception and blood
      pressure control.

PMID- 11510953
TI  - A discriminative two-lever test of dizocilpine's ability to reinstate ethanol
      seeking behavior.
AB  - Because ethanol has N-methyl-D-aspartate (NMDA) antagonist effects, we tested
      whether dizocilpine, an NMDA antagonist, reinstates ethanol-seeking behavior.
      Rats were trained to lever-press for a 10% ethanol/2% sucrose (EtOH) or a 3%
      sucrose (Suc) solution using a two-lever (one lever active) procedure (FR2).
      After extinction, rats were injected with ethanol (0.5 g/kg). The EtOH group
      emitted more active than inactive lever presses and the Suc group showed minimal
      responding. Thus, ethanol reinstated ethanol-seeking behavior in a specific
      manner. In contrast, dizocilpine (0.175 mg/kg) increased responding on both
      levers in both groups suggesting a loss of discriminative control. Dizocilpine
      fails to reinstate ethanol-seeking behavior. These data also demonstrate the
      necessity of using a discriminative, two-lever test for drug reinstatement.

PMID- 11510954
TI  - Attenuation of insulin resistance by chronic beta2-adrenergic agonist treatment
      possible muscle specific contributions.
AB  - A possible mechanism by which chronic clenbuterol treatment causes multiple
      physiological changes in skeletal muscle that leads to reduced insulin resistance
      in the obese Zucker rat (falfa) was investigated. Animals were gavaged with
      clenbuterol (CB) (0.8 mg x kg(-1) day(-1)), terbutaline (TB) (1.0 mg x kg(-1)day(
      1)), or control (CT) vehicle for six weeks. Oral glucose tolerance and insulin
      responses were markedly improved in CB rats and impaired in TB rats. CB treatment
      caused a 24-34% gain in muscle mass in all muscle fiber types, and increases in 3
      O-methyglucose transport (2-fold) and GLUT4 concentration (57%) in fast twitch
      glycolytic (FG) muscle. Oxidative capacity was reduced in both FG (47%) and fast
      twitch oxidative (FO) muscle (30%), but not in slow twitch oxidative (SO) muscle.
      Null model analysis for receptor occlusion demonstrated that most functional beta
      adrenoceptors were lost in FO (82%) and FG (89%) fibers, but not in SO fibers. We
      propose that hypertrophy is the result of continuous direct activation of beta
      adrenoceptors while loss in oxidative capacity may be the result of receptor down
      regulation. Improvements in insulin resistance may have been due, in part, to
      both increases in lean body mass and specific adaptations in FG muscle.

PMID- 11510955
TI  - A sex-related difference in the hypertrophic versus hyperplastic response of
      vascular smooth muscle cells to repeated passaging in culture.
AB  - Activation of growth of vascular smooth muscle cells (VSMC) in adults
      participates in pathogenesis of dysplastic diseases of the vascular system. In
      this study, we examined the impact of gender of rat donors on the degree of
      hyperplastic and hypertrophic responses of VSMC in cultures subjected to repeated
      passaging. The cells were derived from the outgrowth zone of explants of the
      thoracic aorta and were studied up to passage 45. Under these conditions, the
      cells undergo repeated growth stimulation by the serum growth factors mimicking
      some pathological situations in vivo. At lower passages (5-7), the cells from
      both sex donors did not differ significantly in their doubling time, maximum
      population density, protein content and ploidy. At higher passages (40-45), we
      found that the hyperplastic response, monitored by doubling time and BrdU
      revealed DNA synthesis, was more intense in VSMC of male origin. In contrast,
      female-derived cells reacted by more prominent hypertrophic changes. The latter
      included a relatively higher increase in the volume and protein content of cells.
      As indicated by the DNA content histograms and chromosome numbers, these cells
      also showed a higher degree of passage-dependent polyploidization. In addition,
      the female-derived VSMC were found to be more effective in adhesion to the growth
      support evidenced by wider spreading and higher resistance of these cells to
      trypsin-mediated detachment as well as higher expression of some integrin and
      cytoskeletal molecules. These features could partly account for the slower
      proliferation and polyploidization of these cells. The results suggest that rat
      VSMC populations of male and female origin contain cells which are intrinsically
      different with respect to their capability of reacting to growth stimuli. The
      lower responsiveness of female-derived cells to growth stimuli may contribute to
      less frequent formation of hyperplastic vascular lesions in female organisms.

PMID- 11510956
TI  - Histopathological features and modulation of type IV collagen expression induced
      by Pseudomonas aeruginosa lipopolysaccharide (LPS) and porins on mouse skin.
AB  - BACKGROUND: Pseudomonas aeruginosa (P. aeruginosa) is responsible for serious
      infections in the immunocompromised host. Many skin lesions induced by P.
      aeruginosa have been described. Few investigations have been performed on the
      local action of P. aeruginosa components. OBJECTIVES: To shed light on the "in
      vivo" activity of lipopolysaccharide (LPS) and porins extracted from P.
      aeruginosa, by verifying their effects after inoculation in mouse skin through
      the observation of histological changes and immunohistochemical expression of
      collagen IV. RESULTS: Both substances were able to induce a similar inflammatory
      process and a characteristic reversible change in collagen IV distribution.
      Interestingly, a fibroblast increase was observed at 24 h in the skin treated
      with porins, while it appeared later in the skin treated with LPS. Besides these
      changes, porins particularly increased collagen edema, together with disgregation
      of hypodermal structures. Moreover "in vitro", porins were able to stimulate
      fibloblasts 3T3 to convert 72 kDa type IV collagenase into the activated 62 kDa
      form and to release the 92 kDa collagenase. CONCLUSION: LPS and porins, released
      by gram-negative bacteria during cell growth and lysis, interact with the host at
      target cells, such as keratinocytes, fibroblasts and immunocompetent cells, thus
      contributing significantly to the pathogenesis of P aeruginosa skin infections.

PMID- 11510957
TI  - Visualization of bioavailable liposomal doxorubicin using a non-perturbing
      confocal imaging technique.
AB  - Commonly employed tissue processing techniques can significantly alter tissue
      drug distribution patterns for liposomal encapsulated drugs by virtue of drug
      leakage via loss of membrane integrity. We report here a method that has been
      developed to determine the fluorescence of bioavailable doxorubicin (DOX) in
      tissues after administration of liposomal DOX formulations. A non-perturbing
      confocal fluorescence microscopy (CFM) technique with image processing analysis
      was used with unprocessed fresh tissues. This method takes advantage of the fact
      that considerable quenching occurs when DOX is within liposomes, leading to the
      selective visualization of the fluorescence due to DOX released from liposomes.
      We demonstrate that fresh tissue confocal imaging can be applied to provide
      detailed drug distribution information with improved accuracy and is a superior
      method for analyzing tissue distribution of liposome entrapped fluorescent
      agents.

PMID- 11510958
TI  - Synaptic behaviour of some structural and numerical chromosome anomalies in
      female and male rats (Rattus norvegicus).
AB  - The processes of synapsis and synaptic adjustment have been detected in some
      structural and numerical anomalies in two female rat foetuses and in one male rat
      in the course of a study on X-ray genotoxicity. The synaptic characteristics and
      adjustment of one pericentric inversion and a deletion have been analysed by
      electron microscopy in synaptonemal complex spreads from two female foetuses, and
      the synaptic behaviour of a trisomy has been studied in a testicular biopsy from
      an adult male. In a large proportion (from 50% to 90%) of the analysed cells, the
      abnormal meiotic configuration could not be detected either because the anomaly
      was present in mosaic from trisomy or because synaptic adjustment had already
      taken place (inversion) or as result of a combination of two of the above
      (deletion).

PMID- 11510959
TI  - Development and progression of malignancy in human colon tissues are correlated
      with expression of specific Ca(2+)-binding S100 proteins.
AB  - The expression levels of seven different S100 proteins (S100A1, S100A2, S100A3,
      S100A4, S100A5, S100A6, and S100B) were characterized by immunohistochemistry in
      the epithelial versus connective tissues of a series of 35 colon specimens,
      including 6 normal samples, 5 adenomas with low-grade dysplasia, 5 adenomas with
      high-grade dysplasia, and 19 cancers. The results showed that S100A2, S100A3, and
      S100B proteins could not (or only marginally) be detected in colon tissues. On
      the other hand, the expression of S100A6 increased in epithelial tissues directly
      proportional to the increase of malignancy. The percentage of epithelial (or
      connective tissue) cells expressing S100A4 significantly decreased as the
      malignancy grade increased. The expression level of S100A1 proteins was somewhat
      higher in the connective tissues of normal cases and adenomas with low-grade
      dysplasia than in adenomas with high-grade dysplasia and cancers. This pattern of
      expression was not observed in epithelial tissues. While the node-positive
      cancers did not express S100A1, about half of the node-negative specimens did.
      The expression levels of S100A5 were similar in different epithelial tissues.
      However, in the connective tissues the expression levels decreased inversely
      proportional to the increase in pathological grading of the specimens. Therefore,
      the present study implicates several S100 proteins as useful tools for
      histochemical typing of colon cancer malignancy development.

PMID- 11510960
TI  - Effects of orexins A and B on the secretory and proliferative activity of
      immature and regenerating rat adrenal glands.
AB  - Orexins A and B are two hypothalamic peptides, involved in the central regulation
      of feeding, which act through two receptor subtypes, named OX1R and OX2R. OX1R is
      selective for orexin-A, and OX2R binds both orexins. We have investigated the
      effects of three subcutaneous injections of 10 nmol/kg body weight of orexins on
      the secretion and proliferative activity of immature (20-day-old) and
      regenerating rat adrenal cortex. The presence of both OX1R and OX2R mRNAs has
      been detected by reverse transcription-polymerase chain reaction in adult,
      immature and regenerating adrenals. Orexin-A increased corticosterone plasma
      concentration in immature rats, but not in animals with regenerating adrenals.
      Both orexins raised metaphase index (%o of metaphase-arrested cells) in immature
      rat adrenals, orexin-B being more effective than orexin-A. In contrast, both
      orexins equipotently lowered adrenal metaphase index at day 5 (but not day 8) of
      adrenal regeneration. We conclude that orexins (1) stimulate secretion and
      proliferative activity of immature rat adrenals, acting through OX1R and OX2R,
      respectively; and (2) do not affect secretion, but inhibit proliferative activity
      of regenerating adrenals, mainly via the activation of OX2R.

PMID- 11510961
TI  - Sinusoidal 50 Hz magnetic fields do not affect structural morphology and
      proliferation of human cells in vitro.
AB  - The effects of electromagnetic fields on several processes related to cell
      physiology and proliferation are currently being investigated. Although the
      results are still not conclusive and even conflicting, there seems to be a fairly
      good agreement on the early effects of electromagnetic fields on the generation
      of free radicals and on Ca++-intracellular concentration and transport. To
      evaluate the long-lasting consequences of these precocious events, we examined
      the effects of short- and long-term magnetic field exposure on structural
      organization (cytokeratin or actin detection), proliferation (bromodeoxyuridine
      incorporation and propidium iodide staining), colony forming ability and
      viability (trypan blue exclusion test) of highly proliferating MCF-7 cells (from
      human breast carcinoma) and on slowly proliferating normal human fibroblasts
      (from healthy donors). Cells were exposed to either 20 or 500 microT sinusoidally
      oscillating (50Hz) magnetic fields for different lengths of time (1 to 4 days).
      Short (1 day)- and long (4 days)-time exposure to the two intensities did not
      affect MCF-7 growth and viability, colony number and size, or cellular
      distribution along the cell cycle; neither were the cell morphology and the
      intracellular distribution and amount of cytokeratin modified. Similarly, no
      modifications in the actin distribution and proliferative potential were observed
      in normal human fibroblasts. These findings suggest that under our experimental
      conditions, continuous exposure to magnetic fields does not result in any
      appreciable effect in both normal and tumor cells in vitro.

PMID- 11510962
TI  - Potential synergies between matrix proteins and soluble factors on resorption and
      proteinase activities of rabbit bone cells.
AB  - Human growth hormone (GH) has recently been found to stimulate osteoclastic
      resorption, cysteine-proteinase and metalloproteinase activities (MMP-2 and MMP
      9) in vitro via insulin-like growth factor-I (IGF-I) produced by stromal cells.
      The present study investigated the effects of two extracellular matrix components
      (vitronectin and type-I collagen) on hGH- and hIGF-1-stimulated osteoclastic
      resorption and proteinase activities in a rabbit bone cell model. After 4 days of
      rabbit bone cell culture on dentin slices with vitronectin coating, hGH and hIGF
      1 stimulated bone resorption and hIGF-1 upmodulated cysteine-proteinase
      activities. MMP-2 expression (but not resorption, cathepsin or MMP-9 activities)
      was upmodulated by hGH and hIGF-1 on dentin slices coated with type I collagen as
      compared to those without coating. Then, vitronectin was synergistic with hIGF-1
      in the regulation of cysteine-proteinase production whereas collagen showed
      synergy with hGH and hIGF-1 in the regulation of MMP-2 production. Anti
      alphavbeta3 totally abolished the effects of hGH and hIGF-1 on metalloproteinase
      release, but had no influence on cathepsin release. The results suggest that
      cysteine-proteinase modulation is not mediated by alphavbeta3 integrin (strongly
      expressed on osteoclastic surface) whereas the resorption process and
      metalloproteinase modulation are clearly mediated by this integrin. Our finding
      about the collagen coating also suggests that hGH- and hIGF-1-stimulated MMP-2
      activity are mediated, along with alphavbeta3 integrin, by another adhesion
      molecule.

PMID- 11510963
TI  - Short-term neuropathological aspects of in vivo suicide gene transfer to the F98
      rat glioblastoma using liposomal and viral vectors.
AB  - To date, only few preclinical protocols on liposomal suicide gene transfer in
      tumors have been published, none of which directly compared viral to liposomal
      vectors in terms of immunoreactivity and efficacy. We thus studied the
      neuropathological alterations in 80 rats being treated for glioblastoma using
      liposomal and, for comparison, adenoviral and retroviral suicide gene transfer
      approaches to identify vector-associated efficacy and toxicity for further
      clinical studies. 62 rats served as controls. F98 tumors were established in
      Fisher rats and transfected in vivo with the thymidine kinase gene of herpes
      simplex virus (HSVtk) by a single intratumoral application and an implanted
      intratumoral continuous delivery system. Three days later ganciclovir was given
      intraperitoneally for 14 days. The animals were sacrificed 17 days post completed
      gene transfer. Brains were examined histologically and immunohistochemically
      using markers for immunocompetent cells. Ten animals showed complete tumor
      regression; they all belonged to the liposomal and adenoviral groups. In 6 of 10
      experimental groups considerable numbers of lymphocytes along the margins of the
      regression cavities could be observed. Control animals of the liposomal and
      adenoviral groups showed only little lymphocytic infiltration, underlining the
      minimal immunogenicity of these carriers. In contrast, the retroviral control
      group featured a high lymphocyte infiltration. In summary, this study indicates
      that, in terms of both efficacy and immunoreaction, liposomes are as appropriate
      as adenoviruses in the treatment of rat glial tumors using suicide gene transfer
      strategies.

PMID- 11510964
TI  - Widespread cellular distribution of aldehyde oxidase in human tissues found by
      immunohistochemistry staining.
AB  - Aldehyde oxidase (EC 1.2.3.1) is a xenobiotic metabolizing enzyme that catalyzes
      a variety of organic aldehydes and N-heterocyclic compounds. However, its precise
      pathophysiological function in humans, other than its xenobiotic metabolism,
      remains unknown. In order to gain a better understanding of the role of this
      enzyme, it is important to know its exact localization in human tissues. In this
      study, we investigated the distribution of aldehyde oxidase at the cellular level
      in a variety of human tissues by immunohistochemistry. The enzyme was found to be
      widespread in respiratory, digestive, urogenital, and endocrine tissues, though
      we also observed a cell-specific localization in the various tissues studied. In
      the respiratory system, it was particularly abundant in epithelial cells from the
      trachea and bronchium, as well as alveolar cells. In the digestive system,
      aldehyde oxidase was observed in surface epithelia of the small and large
      intestines, in addition to hepatic cells. Furthermore, the proximal, distal, and
      collecting tubules of the kidney were immunostained with various intensities,
      while glomerulus tissues were not. In epididymus and prostate tissues, staining
      was observed in the ductuli epididymidis and glandular epithelia. Moreover, the
      adrenal gland, cortex, and notably the zona reticularis, showed strong
      immunostaining. This prevalent tissue distribution of aldehyde oxidase in humans
      suggests some additional pathophysiological functions besides xenobiotic
      metabolism. Accordingly, some possible roles are discussed.

PMID- 11510965
TI  - Expression of clusterin in Crohn's disease of the terminal ileum.
AB  - Crohn's disease (CD) is a chronic inflammatory intestinal disorder with
      disturbance and injury of the intestinal mucosal barrier, in which various
      proinflammatory molecules as well as molecules with antiinflammatory activity and
      cytoprotective function are found to be expressed. We investigated whether
      clusterin, a multifunctional cytoprotective protein, is upregulated in Crohn's
      disease, because augmented expression of clusterin is seen in many organs
      following various forms of tissue injury. Human actively and inactively inflamed
      ileal tissues from CD patients as well as normal intestinal specimens from
      control patients (normal ileum) were investigated by Western blot analysis,
      immunohistochemisty and in situ hybridization. As compared with controls, a
      strongly enhanced expression of clusterin was found in CD tissues, correlating
      with disease activity. Immunohistochemistry and in situ hybridization analysis
      revealed foci of crypts almost completely lined by clusterin expressing
      enterocytes in CD, a feature that was never seen in controls. Such crypts
      appeared especially within the morphologically intact mucosa apart from erosive
      or ulcerative lesions. Besides epithelia, clusterin was also expressed by
      inflammatory mononuclear cells. Enhanced expression of clusterin by crypt
      epithelia might reflect a cytoprotective function of the protein in order to
      prevent further injury of the intestinal mucosal barrier in CD.

PMID- 11510966
TI  - Effects of ethanol on the ultrastructure of the hamster femur.
AB  - Several previous studies have indicated that chronic ingestion of ethanol exerts
      harmful effects on bones. However, few data are available concerning the effects
      of ethanol on the ultrastructure of bone. To further elucidate the effects of
      ethanol on bone, we studied the morphology of femur in golden hamsters after long
      term treatment with ethanol. Six-week-old male hamsters were divided into 4
      groups. Ethanol-treated animals were given ethanol at a concentration of 7% with
      food and water freely available, whereas the pair-fed animals (weight-matched to
      ethanol hamsters) had tap water available as the only drinking fluid. The femur
      weight, blood ethanol and serum calcium concentrations were determined after 3
      and 5 months. The bone mineral density (BMD) of the whole body was measured
      before and after the experiment. Femurs of both sides were dissected and
      processed for morphometric measurement, light microscopy, scanning and
      transmission electron microscopy. In the ethanol-treated hamsters, BMD of the
      whole body and the weight of femur tended to decrease when compared with those of
      the controls. Light microscopy and scanning electron microscopy showed that the
      trabecula in the distal end of the femur from ethanol-treated hamsters were
      thinner than those of the controls. We also observed the disrupted swollen
      mitochondria of the femoral osteoblasts and osteocytes in the ethanol-treated
      hamsters. No significant difference in serum calcium levels and femoral
      osteoclasts was found. These results indicate that long-term treatment with
      ethanol results in disruption of femoral osteoblasts and reduction of bone mass
      in trabecular bone.

PMID- 11510967
TI  - Earliest lymphoid colonization of neonatal rat lymph nodes: an antigen-specific
      process?
AB  - The present work studied the little known process of lymphoid cell colonization
      of neonatal lymph nodes, while considering the nodal site of entry of circulating
      lymphoid cells and the either random or antigen-specific character of the
      process. Tissue sections of a mesenteric, cervical and popliteal node from each
      of 57 rats, aged 4 hours to 3 weeks, were analysed. Observations bear on the
      relative importance of the implication of the subcapsular sinus versus venules of
      nodes, and the composition of their emerging lymphoid cell population by
      determining the proportion of lymphocytes and blast-related cells. At 16-20 hours
      after birth, cell counts yielded a mean proportion of 84% for blast-related cells
      which decreased to 18% at 3 weeks. These percentages are compatible with values
      expected for a selective antigen-specific entry of lymphoid cells in nodes, not
      with values that would result from a random entry of lymphocytes. Moreover,
      observations revealed that by far most colonizing cells initially enter nodes
      carried by the afferent lymph, little via their venules.

PMID- 11510968
TI  - Ultrastructural observations on the microvasculature in advanced gastric
      carcinomas.
AB  - The ultrastructural features associated with vascular permeability in 9 cases of
      advanced gastric carcinomas were studied, and compared with that of control non
      neoplastic mucosa. Tumour microvasculature showed features in common with those
      of control mucosa, including complete basal lamina, well-developed
      interendothelial junctions, fenestrations and caveolae. Some tumour blood vessels
      showed endothelial cell swelling accompained by luminal narrowing and
      perivascular fibrosis. In 2 out of 9 cases, there were endothelial attenuation
      with numerous fenestrations and vesiculo-vacuolar organelles. The vesiculo
      vacuolar organelle is a recently described cytoplasmic structure found in the
      endothelial cells lining tumour microvessels and normal venules and which
      provides an important pathway for extravasation of circulating macromolecules.
      Our ultrastructural data suggest that advanced gastric carcinomas share with
      experimental tumour models in vivo only some morphologic features associated with
      hyperpermeability including fenestration, endothelial attenuation and vesiculo
      vacuolar organelles. The implications of perivascular fibrosis on the delivery of
      immune cells to gastric carcinomas are discussed.

PMID- 11510969
TI  - Morphological identification of the lipid-storing cells in golden hamster
      parathyroid glands after vitamin A treatment.
AB  - We investigated hamster parathyroid glands of different ages using electron
      microscopy and found a new cell type in young, adult and senile hamsters. Theses
      special cells were located in interstitial tissues and invariably contained
      several lipid droplets within the cytoplasm. The cells showed an elongated
      spindle with some cell processes. The cells contained small Golgi complexes and
      moderate cisternae of the granular endoplasmic reticulum. The morphological
      characteristics of these cells were mostly the same as those of lipid-storing
      cells in other organs (Yamada and Hirosawa, 1976). After vitamin A
      administration, the lipid droplets in these cells markedly increased in number
      and also in volume density. The other morphological features of these cells
      resembled those of the control animals. We called these cells parathyroid lipid
      storing cells. They may incorporate and store vitamin A within the lipid
      droplets. They can be classified as one of the cellular components in hamster
      parathyroid gland.

PMID- 11510970
TI  - Evidence that dendritic cells infiltrate atherosclerotic lesions in
      apolipoprotein E-deficient mice.
AB  - Earlier we reported that atherosclerotic lesions of apoE-deficient mice contained
      cells which stained positively with anti-S-100 antibody and that cells exhibiting
      the ultrastructural features of dendritic cells were present in the aortic
      lesions. These observations suggested that dendritic cells might be involved in
      mouse atherosclerosis. By employing DEC-205 and MIDC-8 antibodies specific for
      dendritic cells, the present study has established that dendritic cells indeed
      accumulate in atherosclerotic lesions of apoE-deficient mice. Finding dendritic
      cells infiltrating atherosclerotic lesions in apoE-deficient mice offers the
      possibility of investigating the migratory routes of dendritic cells and their
      involvement in T-cell activation.

PMID- 11510971
TI  - The immunohistochemical expression of stress-response protein (srp) 60 in human
      brain tumours: relationship of srp 60 to the other five srps, proliferating cell
      nuclear antigen and p53 protein.
AB  - This study analyzed the expression of stress-response (heat-shock) protein 60
      (srp 60) in a series of 158 human brain tumours. Immunohistochemical procedures
      were employed; cells of the human cervical cancer line HeLa S3 exposed to
      hyperosmolar stress served as positive controls. Deposits of reaction products
      were found in the cytoplasm. Approximately half of the glioblastomas multiforme
      (17/31), breast carcinoma metastases (6/10), and lung carcinoma metastases (5/11)
      as well as about one-third of the astrocytomas (5/13) and meningiomas (8/23) had
      tumour cells that expressed srp 60. A positive reaction for srp 60 was also seen
      in some medulloblastomas (2/16), primitive neuroectodermal tumours (PNETs)
      (2/11), schwannomas (2/21), and pituitary adenomas (2/7), but no positive
      reactions were observed with oligodendrogliomas and ependymomas. Compared with
      srp 60-negative tumours, srp 60-positive tumours coexpressed one or more stress
      related proteins, among which srp 90, srp 72, srp 27, alphaB-crystallin and
      ubiquitin occurred with higher frequencies; a high correlation between srp 60 and
      the other five srps (0.88 - 0.97, p<0.01, Pearson correlation coefficient) was
      observed in srp 60-positive tumours. In contrast, the correlation coefficient in
      srp 60-negative tumours was not significant (-0.26 - 0.71). There was a tendency
      for the proliferating cell nuclear antigen (PCNA)-labeling index to be higher in
      glioblastomas, astrocytomas, medulloblastomas, PNETs, and breast and lung
      carcinoma metastases that expressed srp 60 than in those that did not. No
      significant immunohistochemical reactions of srp 60, PCNA and p53 protein were
      seen with sections of normal brain tissues. We conclude that primary and
      metastatic tumours of the brain produce srp 60 and that srp 60 in certain brain
      tumour cells may coexpress the other five srps. In addition, srp 60 expression
      might depend, in part, on proliferating potential.

PMID- 11510972
TI  - Potential role of a new anti-beta3 integrin antibody in the development of
      intimal hyperplasia after vascular surgery: an in vitro smooth muscle cell model.
AB  - The occurrence of intimal hyperplasia after vascular surgery is an ongoing
      concern in current clinical practice. Among the many factors involved in the
      development of this pathology, platelet adhesion and myointimal proliferation
      play a major role. Both these processes are mediated by integrins (mainly
      alphavbeta3 integrins). Over the past years, several substances have been
      designed to delay or inhibit the cell proliferation that leads to hyperplasia and
      mainly include monoclonal antibodies directed against integrins. The aim of the
      present study was to evaluate the effects of an antibody denoted P37 (anti beta3
      integrin) on human smooth muscle cells (SMC) and its role in blocking the B3
      subunit. To this end, SMC from human umbilical artery were cultured in the
      presence or absence of the cell substrate vitronectin (VN) and incubated with
      P37. After 4 days of treatment, determination was made of cell proliferation and
      migration. Smooth muscle cells grown on VN showed increased proliferation and
      migration compared to control VN-free cultures. However, the presence of P37 in
      the culture medium inhibited proliferation and reduced migration. Combined
      treatment with VN and P37 led to improved proliferation but VN was unable to
      reverse the effects on migration observed in the former cultures. Results suggest
      that in vitro, P37 is capable of blocking human SMC beta3 integrins and thus
      impedes cell proliferation and migration These findings may have clinical
      implications related to modulation of the development of hyperplasia.

PMID- 11510973
TI  - Scanning electron microscopy and calcification in amelogenesis imperfecta in
      anterior and posterior human teeth.
AB  - Teeth fragments from members of a family clinically and genetically diagnosed as
      having amelogenesis imperfecta were studied by scanning electron microscopy and X
      ray microprobe analysis to establish the morphological patterns and the
      quantitative concentration of calcium in the enamel of anterior (canine, incisor)
      and posterior (premolar and molar) teeth. The prism patterns in the enamel of
      teeth from both regions were parallel or irregularly decussate, with occasional
      filamentous prisms accompanied by small, irregularly rounded formations.
      Prismless enamel showed the R- and P-type patterns. Calcium levels in enamel of
      amelogenesis imperfecta and control teeth differed significantly between anterior
      and posterior teeth, indicating that the factors that influence normal
      mineralization in different regions of the dental arch are not altered in the
      process of amelogenesis imperfecta.

PMID- 11510974
TI  - Colonic endocrine cells in rats with chemically induced colon carcinoma.
AB  - Colonic carcinoma was induced in male Sprague-Dawley rats by injecting them with
      1,2-dimethylhydrazine dihydrochloride. Control rats were injected with EDTA
      solution. Tissue specimens of colon from four groups of animals: (i) rats without
      tumour, (ii) with dysplasia and lymphoid hyperplasia, (iii) with colonic
      adenocarcinoma, and (iv) controls, were investigated. The colonic endocrine cells
      were detected by immunocytochemistry and quantified by computerised image
      analysis. Peptide YY (PYY)- and serotonin-immunoreactive cells were found in the
      colon of all the groups investigated. There were few somatostatin- or
      enteroglucagon-immunoreactive cells and no pancreatic polypeptide (PP)
      immunoreactive cells in the colon of any of the groups studied. The density of
      PYY-immunoreactive cells increased significantly in rats with dysplasia and
      lymphoid hyperplasia and in rats with colon carcinoma. There was no statistically
      significant difference as regards cell secretory index (CSI) or nuclear area of
      PYY-immunoreactive cells in any of treated groups examined. Nor was there any
      statistically significant difference between all treated animal groups and
      controls, as regards cell density, CSI, or nuclear area of serotonin
      immunoreactive cells. The present observations in an animal model of human colon
      carcinoma support the assumption that neuroendocrine peptides in the gut are
      involved in the carcinogenesis of colorectal carcinoma. However, The nature of
      the changes in the colonic endocrine cells observed here differed from those in
      patients with colon carcinoma, possibly due to a difference between the response
      of young rats to an induced colon carcinoma and a spontaneously developed
      carcinoma in elderly humans, or due to a species difference.

PMID- 11510975
TI  - Acute toxicity of anionic surfactants sodium dodecyl sulphate (SDS) and linear
      alkylbenzene sulphonate (LAS) on the fertilizing capability of gilthead (Sparus
      aurata L.) sperm.
AB  - In the present work we have evaluated and compared the acute toxicity of two
      anionic surfactants, Sodium Dodecyl Sulphate (SDS) and Linear Alkylbenzene
      Sulphonate (LAS) on the fertilizing capability of gilthead Sparus aurata L.
      sperm. The criterion used to judge exposure effectiveness was fertilization
      success. Spawned eggs and sperms were collected from adult giltheads. Sperms were
      dosed separately with different concentrations of SDS and LAS for 60 minutes.
      After this period, sperms and eggs were combined for 20 minutes during which
      fertilization took place. Finally, the number of fertilized eggs were counted and
      recorded to estimate the percentage of fertilization. Exposure to SDS and LAS
      concentrations of 0.3, 0.6, 1.5, 3 and 6 mg/L for 60 minutes caused a significant
      inhibitory effect on fertilization success in gilthead Sparus aurata L.. In
      addition, the EC50 value for gilthead fertilization after sperm exposure was
      found to be 2.8 mg/L and in the case of LAS it was of 2.6 mg/L. The comparison of
      the results from SDS and LAS shows that the latter has a stronger negative effect
      on sperm viability than SDS.

PMID- 11510976
TI  - Neurotransmitters, neuromodulators, and neurotrophin receptors in the gut of
      pantex, a hybrid sparid fish (Pagrus major x Dentex dentex). Localizations in the
      enteric nervous and endocrine systems.
AB  - The gut of Pantex, a sparid hybrid fish (Pagrus major x Dentex dentex) with a
      great potential importance for the Italian aquaculture, was histochemically and
      immunohistochemically investigated in order to evidence components of the
      intramural nervous and diffuse endocrine systems. The general structural aspects
      of the intramural nervous system were shown by the Nissl-thionin staining. As in
      most other fish, it was only organized in the myenteric plexus.
      Acetylcholinesterase (AChE) activity was observed in both nerve cell bodies and
      terminals all along the gut. The NADPH-diaphorase reactivity too, possibly linked
      to the synthesis and release of nitric oxide, was present in nerve cell bodies
      and nerve terminals of the oesophagus, stomach and intestine. In addition, the
      intramural nervous system was shown to contain Trk (tyrosinekinase) receptors for
      neurotrophin, as evidenced by Trk A-, Trk B- and Trk C-like immunoreactivities,
      thus suggesting an involvement of neurotrophin in the function of this system.
      Trk B- and Trk C-like immunoreactivities were detected in epithelial endocrine
      cells, too. The additional presence of serotonin- and metenkephalin-like
      immunoreactivities in numerous endocrine cells in the epithelial layers of the
      stomach and intestine was showed.

PMID- 11510977
TI  - Ultrastructural study of ovine pulmonary pasteurellosis: involvement of
      neutrophils and macrophages.
AB  - Pasteurellosis is a common infectious disease characterised by fibrinous
      pneumonia and involving neutrophils and macrophages. This study aimed to
      determine the timing and extent of the pathogenic involvement of these cell
      elements in lesions induced in experimentally-infected lambs. A concentration of
      approximately 3x10(8) bacteria/ml. was inoculated into 30 two-month-old disease
      free Merino lambs. Five lambs were assigned to each of five experimental batches,
      slaughtered on days 1, 3, 7, 11 and 15 following intratracheal inoculation, and
      to one control batch inoculated with a sterile solution. One control animal was
      slaughtered at the same time as each experimental batch. More characteristic
      lesions occur in bronchioles, peribronchial tissue and alveoli and are
      characterised by fibrinous processes. From the start of the experiment,
      epithelial-cell disruption and loss of microvilli were apparent; cell debris,
      desquamate cells and bacterial elements were observed in bronchiolar lumina,
      embedded in a fibrillar granular material. Alveolar structures displayed fewer
      neutrophils and macrophages, containing phagocytic vacuoles. Laminar bodies were
      apparent in type II pneumocytes. The interseptal area contained similar cell
      types, as well as abundant edema. In the course of the experiment, macrophage
      numbers increased in all the areas involved, with signs of intense phagocytic
      activity. The final phase of the experiment was characterised by a mild
      interseptal infiltrate and by clear alveolar lumina.

PMID- 11510979
TI  - Enteric plexus and interstitial cells of Cajal: interrelationship in the stomach
      of Podarcis hispanica (Reptilia). An ultrastructural study.
AB  - The ultrastructure organization of the stomach enteric plexus was examined in the
      lizard Podarcis hispanica. The ganglions of the myenteric plexus present a low
      number of nerve cell bodies with a peculiar nucleus, which occasionally establish
      direct contacts with cells of the circular muscle layer. Glial cells are smaller
      than the neurones, and their nucleus is very electron-dense. They surround the
      axons that constitute the fibres of the myenteric plexus. Four main types of axon
      profile are described in a morphological consideration of the vesicle population.
      In the interstice of the circular muscle layer we describe two types of
      interstitial cells that, due to their ultrastructural characteristics, may be
      equivalent to the interstitial cells of Cajal which have been described in
      mammalians. These cells shows parallel distribution to the stomach nerve
      plexuses, establishing close contacts with them through their long cytoplasmic
      prolongations. By means of small gap-like unions, they contact both each other
      and the smooth muscle cells near them. We describe a submucous plexus, where
      neuronal bodies are scattered among bundles of nervous fibres, some of which are
      myelinated. A mucous plexus with isolated neurones is located in the lamina
      propria. Axonal varicosities containing vesicles contact with the cells of the
      mucous. Interconnected interstitial cells may also be found in this plexus.

PMID- 11510978
TI  - Immunohistochemical profile of galectin-8 expression in benign and malignant
      tumors of epithelial, mesenchymatous and adipous origins, and of the nervous
      system.
AB  - This study aims to investigate whether the immunohistochemical expression of
      galectin-8 could be used as a diagnostic marker in tumor tissues of various
      histogenetic origins including specimens from epithelial (n=145), mesenchymatous
      (n=16), adipous (n=10) and central and peripheral nervous system (n=25) tissue,
      and 4 mesotheliomas. Immunohistochemical reactions were carried out with a
      polyclonal anti-galectin-8 antibody and histological slides from tissues derived
      from the files of the Laboratory of Anatomopathology of University Erasmus
      Hospital, Brussels. Formalin-fixed paraffin-embedded tissues of 45 normal cases
      as well as 41 benign and 114 malignant tumors were studied. Marked decreases in
      immunohistochemical galectin-8 expression were observed in colon (p=0.001),
      pancreas (p=0.007), liver (p=0.0008), skin (p=0.002) and larynx (p=0.02) tissue
      when comparing malignant tissue to normal tissue and/or benign tumors. The
      reverse relationship was observed for breast tissue (p=0.007). No statistically
      significant differences (p>0.05) were detected when comparing normal tissue
      and/or benign to malignant tumors in lung, bladder, kidney, prostate and stomach
      tissue. Significant galectin-8 expression was also measured in non-epithelial
      tissue including tumors of the central and peripheral nervous system as well as
      in skeletal muscle and mesotheliomas. Immunohistochemical monitoring of galectin
      8 thus reveals an organ-type-dependent regulation of expression upon malignant
      transformation of various tissue types of epithelial origin. This observation
      will prompt further studies to delineate any relationship with prognosis.

PMID- 11510980
TI  - Gene therapy strategies in neurodegenerative diseases.
AB  - Treatment of neurodegenerative diseases by classical pharmacotherapy is
      restricted by blood-brain barrier which prevents access to the brain of
      potentially therapeutic molecules. Recent progress in the knowledge of
      pathophysiological molecular processes, and in the development of molecular
      biotechnology have opened the way to new therapeutic interventions for these
      disorders. This chapter reviews the most recent gene therapy strategies using
      experimental models for neurodegenerative diseases.

PMID- 11510981
TI  - Caspase inhibition: a potential therapeutic strategy in neurological diseases.
AB  - Caspases are intracellular proteases that participate in apoptotic pathways in
      mammalian cells, including neurons. Here we review evidence that caspase
      inhibition, through pharmacological or molecular means, may inhibit neuronal cell
      death in a number of in vitro and in vivo models of neurological disease. It has
      recently become clear that, at least in most cell culture models, caspase
      inhibition offers only transient protection, and that a caspase-independent death
      eventually occurs. This may be due to irreversible caspase-independent
      alterations at the level of the mitochondria. Despite concerns that targeting
      caspases alone may prove insufficient to truly reverse the effects of various
      death stimuli, in vivo studies indicate that caspase inhibition promotes survival
      and functional outcome in a variety of neurological disease models. In addition,
      studies of human post-mortem material suggest that caspases are activated in
      certain human neurological diseases. Caspase inhibition may therefore provide a
      novel strategy for the treatment of such disorders. Caspases, through the
      generation of toxic fragments of critical protein substrates, may also be
      involved in earlier steps of neuronal dysfunction, such as protein aggregation in
      Huntington's and Alzheimer's disease, and therefore caspase inhibition may be of
      additional value in the treatment of these particular disorders.

PMID- 11510982
TI  - F9 embryocarcinoma cells: a cell autonomous model to study the functional
      selectivity of RARs and RXRs in retinoid signaling.
AB  - Mouse F9 embryocarcinoma (EC) cells constitute a well established cell-autonomous
      model system for investigating retinoid signaling in vitro as, depending on
      culture conditions, retinoic acid (RA) can induce their differentiation into
      either primitive, parietal or visceral extraembryonic endoderm-like cells. These
      RA-induced differentiations are accompanied by decreases in proliferation rates,
      modifications of expression of subsets of RA-target genes, and induction of
      apoptosis. To elucidate the roles played by the multiple retinoid receptors (RARs
      and RXRs) in response to RA treatments, F9 EC cells lacking one or several RARs
      or RXRs were engineered through homologous recombination. Mutated RARs and/or
      RXRs were then reexpressed in given RAR or RXR null backgrounds. WT and mutant
      cells were also treated with different combinations of ligands selective for RXRs
      and/or for each of the three RAR isotypes. These studies lead to the conclusion
      that most RA-induced events (e.g. primitive and visceral differentiation, growth
      arrest, apoptosis and activation of expression of a number of genes) are
      transduced by RARgamma/RXRalpha heterodimers, whereas some other events (e.g.
      parietal differentiation) are mediated by RARalpha/RXRalpha. heterodimers. They
      also demonstrate that both AF-1 and AF-2 activation functions of RARs and RXRs,
      as well as their phosphorylation, are differentially required in these RA-induced
      events. In RARgamma/RXRalpha heterodimers, the phosphorylation of RARgamma is
      necessary for triggering primitive differentiation, while that of RXRalpha is
      required for growth arrest. On the other hand, phosphorylation of RARalpha is
      necessary for parietal differentiation. Thus, retinoid receptors are
      sophisticated signal integrators that transduce not only the effects of their
      cognate ligands, but also those of ligands that bind to membrane receptors.

PMID- 11510983
TI  - Heat-induced antigen retrieval of epoxy sections for electron microscopy.
AB  - The purpose of this manuscript is to review the literature on the use of heat
      induced antigen retrieval methods to enhance the immunolabeling of epoxy sections
      at the electron microscopical level. The history of the development of antigen
      retrieval by heating formaldehyde fixed paraffin sections in a buffer solution is
      given in short, and how this technique has been extended to resin sections and in
      particular epoxy sections is explained. Theories for the mechanism of enhancement
      of the immunolabeling of epoxy sections by the heat-retrieval method are
      discussed, and it is finally speculated whether most of the mechanisms for
      antigen retrieval on epoxy sections in heated buffer solution are essentially the
      same as for conventional immunoenhancing by deplastizing and etching. The more
      accelerator used in the processing of the tissue the more intense the
      immunolabeling of the heated epoxy sections becomes. The intensity of
      immunolabeling of the epoxy sections increases with the temperature in the heated
      buffer solution, and the intensity is significantly higher at high autoclave
      temperatures than at 95 degrees C, Heat-induced antigen retrieval is also
      compared with other, conventional techniques for enhancing the immunolabeling of
      epoxy sections.

PMID- 11510984
TI  - Opiomelanins synthesis and properties.
AB  - Opiomelanins represent a new class of synthetic pigments produced by the
      tyrosinase-catalyzed oxidation of opioid peptides and other tyrosine
      aminoterminal peptides. In contrast with dopamelanin, these polymers are fully
      soluble in hydrophilic media, due to the presence of the peptide moiety.
      Opiomelanins show paramagnetism as demonstrated by the EPR spectrum identical to
      that of dopamelanin. The presence of the aminoacidic chain linked to the
      melaninic moiety, influences the electron transfer properties of opiomelanins
      i.e. the ability to oxidize NADH. Like dopamelanin Tyr-Gly-melanin exhibits this
      behaviour whereas leuenkmelanin does not show any oxidizing potential.
      Opiomelanins UV-Vis spectrum is characterized by an absorption band at 330 nm
      which disappears upon acid hydrolysis, H2O2 treatment and under simulated solar
      illumination. Opiomelanins exhibit a fluorescence emission peaked at 440 and 520
      nm if excited at 330 nm. These fluorescence bands are due to the oligomeric units
      and high molecular weight units, respectively. When opioid peptides are allowed
      to react with tyrosinase in the presence of an excess of cysteine,
      cysteinyldopaenkephalins are synthesized. These peptides are furtherly oxidized
      giving rise to pheoopiomelanins. Reactive oxygen species also are able to oxidize
      non enzymatically both enkephalins and cysteinyldopaenkephalins, producing the
      corresponding melanin pigments.

PMID- 11510985
TI  - Role of nitric oxide in murine cytomegalovirus (MCMV) infection.
AB  - Cytomegalovirus (CMV) is a typical pathogen of an opportunistic infection. In
      this review article, various roles of nitric oxide (NO) in murine CMV (MCMV)
      infections, including acute, persistent and latent infections, are discussed. In
      the acute phase of MCMV infection, NO plays a protective role against MCMV
      infection. In contrast, NO has been proven to act as a pathogenic factor in a
      model of MCMV pneumonitis. In MCMV persistent infection, when MCMV was detected
      only in the salivary gland, T cells of mice were modified to produce a massive
      amount of such cytokines as TNF-alpha and IFN-gamma upon in vivo stimulation with
      anti-CD3. These cytokines then induced mRNA for inducible NO synthase (iNOS),
      thus resulting in the production of a large amount of NO. A histochemical study
      demonstrated that NO damaged bronchial epithelial cells, and thereby apparently
      inducing pneumonitis. In the case of a latent infection, when viral DNA was
      detected in the host in spite of the absence of any infectious particle, NO
      increased the amount of persistently-infected MCMV-DNA. As a result, NO was found
      to act as "a double edged sword" in the CMV-host relationship.

PMID- 11510986
TI  - Tracking prostate carcinoma micrometastasis to multiple organs using
      histochemical marker genes and novel cell systems.
AB  - Studies of human prostate carcinoma (PCA) have been hampered by only a few cell
      systems from already-metastatic human disease. We have developed a novel cell
      system by using tissue cultured CWR22R cells from a xenograft of a primary tumor
      from a human patient. These cells were transfected with the bacterial lacZ gene
      to maximize their detection during progression and metastasis in nude mice. LZ
      CWR22R cells are extremely stable for lacZ expression over 25 passages and
      metastasize to lung, liver, and bone from the subcutis - major sites of
      metastasis of the human disease. A matrigel vehicle facilitated development of
      primary tumors and micrometastases in all organs. While some micrometastases
      developed into overt metastases, others remained as micrometastases for long
      periods of time, possibly providing a model of latency of metastatic disease. An
      experimental metastasis model (tail vein injection) also generated
      micrometastases in lung, liver, and bone with differing kinetics of formation and
      stability. Serial sections of many individual lung micrometastases within one
      hour of injection indicated considerable heterogeneity in cellular composition
      (from 1 to 19 cells/site) while liver sites at later times were comprised of only
      1 or 2 cells (the size of bone sites were comparable to those of liver). By
      combining use of these histochemically-tagged PCA cell systems with high
      resolution molecular analyses (laser-capture microdissection), it will now be
      possible to analyze gene expression patterns characteristic of micrometastases
      developing in several different organs.

PMID- 11510987
TI  - Interactions between cerebellar Purkinje cells and their associated astrocytes.
AB  - Some neurons, including cerebellar Purkinje cells, are completely ensheathed by
      astrocytes. When granule cell neurons and functional glia were eliminated from
      newborn mouse cerebellar cultures by initial exposure to a DNA synthesis
      inhibitor, Purkinje cells lacked glial sheaths and there was a tremendous
      sprouting of Purkinje cell recurrent axon collaterals, terminals of which
      hyperinnervated Purkinje cell somata, including persistent somatic spines, and
      formed heterotypical synapses with Purkinje cell dendritic spines, sites usually
      occupied by parallel fiber (granule cell axon) terminals. Purkinje cells in such
      preparations failed to develop complex spikes when recorded from intracellularly,
      and their membrane input resistances were low, making them less sensitive to
      inhibitory input. If granule cells and oligodendrocytes were eliminated, but
      astrocytes were not compromised, sprouting of recurrent axon collaterals occurred
      and their terminals projected to Purkinje cell dendritic spines, but the Purkinje
      cells had astrocytic sheaths, their somata were not hyperinnervated, the somatic
      spines had disappeared, complex spike discharges predominated, and membrane input
      resistance was like that of Purkinje cells in untreated control cultures. When
      cerebellar cultures without granule cells and glia were transplanted with granule
      cells and/or glia from another source, a series of changes occurred that included
      stripping of excess Purkinje cell axosomatic synapses by astrocytic processes,
      reduction of heterotypical axospinous synapses in the presence of astrocytes,
      disappearance of Purkinje cell somatic spines with astrocytic ensheathment, and
      proliferation of Purkinje cell dendritic spines after the introduction of
      astrocytes. Dendritic spine proliferation was followed by formation of
      homotypical axospinous synapses when granule cells were present or persistence as
      unattached spines in the absence of granule cells. The results of these studies
      indicate that astrocytes regulate the numbers of Purkinje cell axosomatic and
      axospinous synapses, induce Purkinje cell dendritic spine proliferation, and
      promote the structural and functional maturation of Purkinje cells.

PMID- 11510988
TI  - Platelet adhesion receptors and (patho)physiological thrombus formation.
AB  - In thrombus formation associated with hemostasis or thrombotic disease, blood
      platelets first undergo a rapid transition from a circulating state to an
      adherent state, followed by activation and aggregation. Under flow conditions in
      the bloodstream, this process potentially involves platelet-platelet, platelet
      endothelium, platelet-subendothelial matrix, and platelet-leukocyte interactions.
      Specific adhesion receptors on platelets mediate these interactions, by engaging
      counter-receptors on other cells, or noncellular ligands in the plasma or matrix.
      The glycoprotein (GP) Ib-IX-V complex on platelets initiates adhesion at high
      shear stress by binding the adhesive ligand, von Willebrand Factor (vWF). GP Ib
      IX-V may also mediate platelet-endothelium or platelet-leukocyte adhesion, by
      recognition of P-selectin or Mac-1, respectively. Other membrane glycoproteins,
      such as the collagen receptor GP VI, may trigger platelet activation at low shear
      rates. Engagement of GP Ib-IX-V or GP VI leads ultimately to platelet aggregation
      mediated by the integrin, alphaIIbbeta3 (GP IIb-IIIa). This review will focus on
      recent advances in understanding structure-activity relationships of GP Ib-IX-V,
      its role in initiating thrombus formation, and its emerging relationships with
      other vascular cell adhesion receptors.

PMID- 11510989
TI  - Cellular and molecular basis of fibrous dysplasia.
AB  - Recent advances have been made in the cellular and molecular mechanisms involved
      in monostotic and polyostotic fibrous dysplasia, a rare nonmalignant disease
      causing bone deformations and fractures. The molecular basis of fibrous dysplasia
      has been clarified when mutations affecting the stimulatory alpha subunit of G
      protein (Gs) have been found in dysplastic bone lesions. The histological
      analysis of dysplastic lesions revealed that the mutations in Gsalpha caused
      abnormalities in cells of the osteoblastic lineage and therefore in the bone
      matrix. Further in vitro analyses of bone cells from mutant dysplastic bone
      lesions revealed that the abnormal deposition of immature bone matrix in fibrous
      dysplasia results from decreased differentiation and increased proliferation of
      osteoblastic cells. Finally, the signaling pathway involved in these osteoblastic
      abnormalities has been identified. It is now apparent that the constitutive
      elevation in cAMP level induced by the Gsalpha mutations leads to alterations in
      the expression of several target genes whose promoters contain cAMP-responsive
      elements, such as c-fos, c-jun, Il-6 and Il-11. This in turn affects the
      transcription and expression of downstream genes and results in the alterations
      of osteoblast recruitment and function in dysplastic bone lesions. These
      mechanisms provide a cellular and molecular basis for the alterations in bone
      cells and bone matrix in fibrous dysplasia.

PMID- 11510990
TI  - Spermiogenesis in the pseudophyllid cestode Eubothrium crassum (Bloch, 1779).
AB  - Spermiogenesis of the pseudophyllidean tapeworm Eubothrium crassum has been
      described by the aid of transmission electron microscopy for the first time.
      Initially, early spermatids form a distal cytoplasmic protrusion, a
      differentiation zone containing a small electron-dense, apically oriented region.
      Out of this region, two centrioles with rootlets develop. The centrioles become
      orientated in the same plane with the appearance of an intercentriolar body. Now,
      the long axes of the rootlets are parallel with each other and with the long axis
      of the nucleus. Two flagella of subsequently unequal length are formed very
      rapidly. Simultaneously, a median cytoplasmic process (MCP) develops distal to
      the flagella. Two arching membranes appear at the base of the differentiation
      zone. Each flagellum, still being in contact with an intercentriolar body,
      rotates to a position parallel with the MCP. The nucleus migrates very rapidly
      into the MCP at this stage. Subsequently, the two flagella fuse with the MCP.
      Finally, the basal bodies with the rootlets detach from the flagella, the
      intercentriolar body changes its structure and spermatids are pinched off from a
      condensing residual cytoplasm at the level of the arching membranes.

PMID- 11510991
TI  - Characterization of a monoclonal antibody reacting with antigen-4 domain of gp900
      in Cryptosporidium parvum invasive stages.
AB  - Cryptosporidium parvum (Protozoa, Apicomplexa) infects the apical surface of
      intestinal epithelial cells, where it grows and divides within a membrane-bound
      parasitophorous vacuole. gp900, an abundant glycoprotein of C. parvum merozoites
      and sporozoites, is localized in micronemes and at the surface of invasive stages
      and participates in the invasion process. Here, we describe a new monoclonal
      antibody (mAb) against gp900. As shown by immunofluorescence of excysted
      parasites and immunoelectron microscopy of infected tissues, the mAb reacted with
      micronemes present in the apical pole of invasive stages. In immunoprecipitation
      experiments, the mAb was shown to react with a high molecular weight antigen co
      migrating with gp900. Finally, three reactive clones were selected upon screening
      of a C. parvum genomic expression library with the mAb; and sequencing of the
      insert from one of them showed a 596 bp sequence identical to the DNA region
      encoding a domain of gp900 identified as antigen 4.

PMID- 11510992
TI  - Inhibitory effect of different UV lamps on the infectivity of taeniid eggs.
AB  - The expanding distribution of alveolar echinococcosis in Hokkaido, Japan
      necessitates a search for control measures, particularly for killing Echinococcus
      eggs; and UV radiation is a potential tool. To determine the effective UV lamp
      and its optimum duration of exposure to inhibit the infectivity of taeniid eggs,
      three UV lamps (UVA, UVB and UVC) with peak emissions at different wavelengths
      were used to irradiate eggs of Taenia taeniaeformis. Irradiation was done in
      durations of 30, 90, 270, 810, 2,430 and 7,290 s. Infectivity of the irradiated
      eggs was tested by oral inoculation into rats. The inhibitory effect of the UV
      lamps at different exposure durations was determined by the reduction in the
      larval cyst establishment and by the delay of larval development. The UVC lamp
      (narrow peak at 254 nm) was found to be the most effective lamp at an exposure
      duration of more than 2,430 s (2,430 mJ/cm2), attaining 100% reduction. Also,
      shorter exposure durations produced a significant effect on the development of
      irradiated eggs in a greater percentage of small cysts (> 1 mm) among the
      metacestodes. Irradiation delayed the development of some cysts, as observed in
      histopathological sections. UVA and UVB lamps were not able to attain 100%
      reduction. It is concluded that the UVC lamp can be used as a tool in sterilizing
      taeniid eggs and is thus a promising method to control echinococcosis, although
      it may require a higher intensity of exposure.

PMID- 11510993
TI  - Ultrastructure of developmental stages of Hemolivia stellata (Apicomplexa:
      Haemogregarinidae) in the cane toad Bufo marinus and in its vector tick Amblyomma
      rotondatum.
AB  - The fine structure of the hemogregarine Hemolivia stellata Petit, Landau, Baccam
      and Lainson, 1990 developmental stages in the cane toad Bufo marinus L. and the
      vector tick Amblyomma rotondatum Koch, 1844 are described. In the liver of the
      toad, merozoites bound by a pellicle were located free and in the cytoplasm, and
      young and encased mature polynucleated meronts were located in a parasitophorous
      vacuole (PV). Premature gametocytes in the erythrocytes were bound by a bilayered
      membranous wall and the mature gametocytes were encased in a bivalved capsule,
      suture sites occurring at both gametocyte extremities. In the tick gut cells,
      oocysts located within a PV formed oblong, pellicle-bound sporokinetes, with a
      small apical complex, a few short rhoptries, and a fragmented crystalloid body.
      Liberated sporokinetes re-entered gut cells to proceed with their differentiation
      into sporocysts within a PV with elaborate rims which suggested engagement in
      active metabolite cross-transport. With maturity, the sporocyst wall gradually
      transformed into a hard capsule. Differences in fine structural development
      between species of Hemolivia and the insect-transmitted Hepatozoon are
      conspicuous. The fine structure and course of development of H. stellata are very
      similar to those of the previously described Hemolivia mariae; their sporokinetes
      differ, however, in having conspicuous rhoptries rather than spherical-granular
      anlagen bodies, and fragmented rather than continuous crystalline bodies.

PMID- 11510994
TI  - Superoxide-dependent and -independent pathways are involved in the transmission
      blocking of malaria.
AB  - Superoxide plays a crucial role in innate immunity to various pathogens. We
      examined the role of superoxides in the transmission of malaria using gp91phox
      knockout (X-CGD) mice that lack the ability to produce superoxide. Mosquitoes
      that fed on X-CGD mice infected intraperitoneally with Plasmodium berghei NK65
      ANKA formed more oocysts than did those that fed on control mice at any day after
      infection. The number of oocysts peaked on day 5 post-infection in X-CGD and
      control mice and then decreased significantly after day 5 post-infection.
      However, on day 7 post-infection, the infectivity of gametocytes in X-CGD mice
      was significantly higher than that in control mice. These results show that two
      pathways, superoxide-dependent and -independent, are involved in the host systems
      regulating the transmission of malaria and inhibiting gametocyte development.

PMID- 11510996
TI  - In vitro effects of anti-Trypanosoma cruzi compounds on HSP60 levels.
AB  - The effect of nifurtimox and 5-nitro-2-thienylmalononitrile (5NO2TM), a novel
      compound with anti-Trypanosoma cruzi activity, upon vitality and HSP60
      immunoreactivity of epimastigotes, has been determined. Both products showed no
      activity against epimastigotes at 0.1 microg/ml, while at 0.5 and 1 microg/ml,
      after 24 h of incubation, densities of these groups were significantly reduced,
      when compared to controls. An enhancement of HSP60 immunoreactivity was observed
      after 24 h in groups treated with 0.5 and 1 microg/ml nifurtimox. On the other
      hand, 5NO2TM had no effect.

PMID- 11510995
TI  - Effect of fasciolicides on the antigenaemia in sheep naturally infected with
      Fasciola hepatica.
AB  - A study was developed to evaluate the influence of triclabendazole (Fasinex) and
      netobimin (Hapasil) the antigenaemia in sheep naturally infected with Fasciola
      hepatica during 16 weeks. A sandwich-ELISA (enzyme-linked immunosorbent assay)
      using a rabbit polyclonal IgG antibody to F. hepatica antigens was employed and
      the data obtained were compared to those from coprological and indirect-ELISA
      techniques. Triclabendazole reduced the values of circulating antigens at weeks 2
      4 post-treatment and faecal output at weeks 2-8 post-treatment, but antibodies
      showed positive values until the end of the study. Netobimin did not reduce
      circulating antigens of the trematode nor egg-excretion; and IgG antibodies did
      not decrease throughout the study.

PMID- 11510997
TI  - Ultrastructural damage of Trypanosoma cruzi epimastigotes exposed to
      decomplemented immune sera.
AB  - The susceptibility of Trypanosoma cruzi epimastigotes to lysis by normal or
      immune sera in a complement-dependent reaction has been reported, but the effects
      induced directly by immune serum depleted of complement remain unstudied. The aim
      of this work was to study the ultrastructural alterations induced in T. cruzi
      epimastigotes by immune mouse or rabbit sera with or without complement. A local
      isolate of T. cruzi (Queretaro) was used in all experiments. Immune sera were
      raised in both mouse and rabbit by immunization with T. cruzi epimastigote
      antigens. Light microscopy showed intense agglutination of epimastigotes when
      incubated with decomplemented mouse or rabbit immune sera. A distinctive
      ultrastructural feature of this agglutination pattern was the fusion of plasma
      membranes and a pattern of intercrossing between subpellicular microtubules.
      Agglutination was associated with fragmentation of nuclear membranes and swelling
      of cytoplasm, Golgi cisternae, endoplasmic reticulum, mitochondria and
      kinetoplast membranes. Agglutinated parasites also incorporated trypan blue
      stain. Results of [3H]-thymidine incorporation confirmed that epimastigotes
      exposed to specific antibodies in the absence of complement were incapable of
      proliferating. Ultrastructural changes observed in epimastigote micrographs
      incubated with decomplemented immune mouse sera were statistically significant
      (P<0.001) when compared with results obtained from images after incubation with
      decomplemented normal mouse sera.

PMID- 11510998
TI  - Growth kinetic study of Tetratrichomonas didelphidis isolated from opossum
      Lutreolina crassicaudata and interaction with a prokaryotic cell.
AB  - Tetratrichomonas didelphidis is a flagellate protozoan found in the intestine,
      cecum and colon of opossums, Didelphis marsupialis. This work reports the
      occurrence of T. didelphidis in another opossum species, Lutreolina
      crassicaudata. The strain was cultivated in monoxenic culture with Escherichia
      coli in Diamond (TYM) medium without maltose and with starch solution (trypticase
      yeast extract-starch), pH 7.5 at 28 degrees C. The growth kinetic study of T.
      didelphidis showed a longer time of growth and a higher number of trophozoites
      when inoculated with E. coli than in axenic cultures, in aerobiosis as well as
      under anaerobic conditions. Scanning electron microscopy showed that the bacteria
      adhered throughout the protozoan body and probably evoked endocytic channels,
      strongly suggesting the existence of endocytosis of rods by T. didelphidis. Our
      preliminary results suggest that the in vitro culture of T. didelphidis depends
      on E. coli as a growth-promoting partner, and requires monoxenic cultivation.

PMID- 11510999
TI  - Cercarial productivity of Fasciola hepatica in Lymnaea truncatula during usual
      and unusual development of redial generations.
AB  - Single-miracidium infections of Lymnaea truncatula by Fasciola hepatica were
      carried out to determine the cercarial productivity of each redial generation
      when the first-appearing mother redia (R1a redia) normally developed (usual
      development of redial generations) or quickly died (unusual development). In both
      developmental patterns of infection, the number of morulae was significantly
      higher in the second-appearing mother rediae (R1b group) than in either the
      daughter rediae from R1a rediae (R2a group) or the rediae from subsequent groups
      (R2b/R3a). The live R1a group did not produce cercariae. The percentages of
      cercariae produced by the R1b, R2a, and R2b/R3a groups were 28.2%, 62.8%, and
      8.9% when the development of redial generations was usual. In contrast, in an
      unusual development, they were 69.3%, 20.3%, and 10.2%, respectively. Cercarial
      production until day 63 post-exposure was essentially provided by the R2a rediae,
      when the development of redial generations was usual, and by the R1b rediae when
      it was unusual.

PMID- 11511000
TI  - Towards the Toxoplasma gondii proteome: position of 13 parasite excretory
      antigens on a standardized map of two-dimensionally separated tachyzoite
      proteins.
AB  - High resolution two-dimensional separation of Toxoplasma gondii tachyzoite lysate
      revealed up to 224 distinct protein spots in Coomassie-stained gel. Computional
      matching of 14 digitized gels yielded a standard two-dimensional proteome map.
      The excretory T. gondii dense granule proteins GRA1-GRA8, S16/acid phosphatase,
      nucleoside triphosphate hydrolase, and H4 were identified by Western blotting of
      both total gel and isolated protein spots. In addition, two excretory antigens
      defined by parasite-specific monoclonal T cells, p36 and p40, were mapped by a
      novel T-cell blotting technique based on electroeluting single protein spots and
      testing the eluates for antigenic activity against the T-cell clones. In summary,
      these results represent a first step in Toxoplasma proteome analysis.

PMID- 11511001
TI  - Molecular phylogenies suggest the oocyst residuum can be used to distinguish two
      independent lineages of Eimeria spp in rodents.
AB  - Using plastid 23S and nuclear 18S rDNA partial sequences for 16 Eimeria species
      from rodents, we compared their molecular phylogenetic inferences with
      morphological features and host specificity. The 16 ingroup taxa included Eimeria
      species which had different morphological features, but were from the same host
      genus or species, and species which had similar morphological features, but were
      from different host families or genera. Molecular phylogenies grouped the 16
      rodent Eimeria species into two major lineages with high bootstrap support:
      lineage A included E. albigulae (from Neotoma), E. arizonensis (Peromyscus,
      Reithrodontomys), E. chaetodipi (Chaetodipus), E. chobotari (Dipodomys), E.
      dipodomlysis (Dipodomys), E. leucopi (Peromyscus), E. onychomysis (Onychomys), E.
      peromysci (Peromyscus) and E. reedi (Perognathus); and lineage B included E.
      falciformis (Mus), E. langebarteli (Peromyscus, Reithrodontomys), E. nieschulzi
      (Rattus), E. papillata (Mus), E. scholtysecki (Dipodomys), E. separata (Rattus)
      and E. sevilletensis (Onychomys). Examination of the morphological features of
      all 16 Eimeria species indicates that only the oocyst residuum shows a clear
      correlation to the phylogenetic relationships determined by the molecular data.
      Species in lineage A all contain one (or more) oocyst residuum in their
      sporulated oocysts, while species in lineage B lack an oocyst residuum in their
      sporulated oocysts. Considering that the host range of the Eimeria species used
      in this study includes nine genera in two families and that each eimeriid lineage
      contains species from both families, it seems likely that the two Eimeria
      lineages split before their host families diverged.

PMID- 11511002
TI  - Histopathology of CNS and nasal infections caused by Trichobilharzia regenti in
      vertebrates.
AB  - In bird infections caused by Trichobilharzia regenti, the central nervous system
      (CNS) represents probably the main route to the nasal cavity, where maturation of
      the parasite occurs. However, in an abnormal mouse host, development is
      incomplete and is accompanied by a strong affinity of the parasite to the CNS. In
      order to explain pathological changes caused by the parasite, a histological
      study of cross-sections from the CNS and nasal cavity was performed. In the CNS
      of duck and mouse, immature flukes were found. Cross-sections showed parasites
      located either in meninges or in matter of various parts of the spinal cord and
      brain. In the spinal cord, the submeningeal location led to a strong inflammatory
      reaction around the schistosomula and resulted in eosinophilic meningitis. In the
      white and gray matter of the spinal cord and in the white matter of the brain, a
      cellular infiltration of spongy tissue surrounded the immature parasites; and we
      observed dystrophic and necrotic changes of neurons, perivascular eosinophilic
      inflammation in the spinal cord and brain, and cell infiltration around the
      central canal of the spinal cord. T. regenti adults and eggs were detected in the
      nasal mucosa of infected ducklings; and aging of the eggs resulted in various
      host reactions, ranging from focal accumulation of cells to the formation of
      granulomas. Histopathological changes may explain symptoms described previously
      for prepatent and patent phases of infections caused by T. regenti, i.e.,
      neuromotor abnormalities in birds and mammals and hemorrhages/petechiae in birds,
      respectively.

PMID- 11511003
TI  - Anti-Acanthamoeba IgG, IgM, and IgA immunoreactivities in correlation to strain
      pathogenicity.
AB  - Several representatives of the genus Acanthamoeba are known as causative agents
      of Acanthamoeba keratitis and granulomatous amoebic encephalitis. These occur
      predominantly in the immunocompromised host, but it is still unclear what primes
      the amoebae for pathogenicity. The aim of this study was to assess possible
      immunological differences between a highly pathogenic and a nonpathogenic
      Acanthamoeba strain. A total of 20 sera, including two sera of Acanthamoeba
      keratitis patients, were tested for anti-Acanthamoeba IgG, IgM, and IgA
      immunoreactivities using immunoblotting. All sera were positive for Acanthamoeba,
      revealing two predominant bands at 29 kDa and at 47 kDa, respectively.
      Interestingly, IgG and particularly IgA immunoreactivity enabled a clear
      discrimination between the pathogenic and nonpathogenic strains. Moreover,
      compared to the control sera, the two sera of Acanthamoeba keratitis patients
      showed rather weak immunoreactivities and they lacked the 29 kDa and the 47 kDa
      band in the IgA immunoblot against the pathogenic strain. The results of our
      study support the assumption that immunological predisposition might also be of
      importance in Acanthamoeba keratitis.

PMID- 11511004
TI  - Infection dynamics of Hemolivia mariae in the sleepy lizard Tiliqua rugosa.
AB  - The blood parasite Hemolivia mariae was experimentally transmitted to lizards
      under laboratory and field conditions. Weekly blood samples from experimentally
      infected lizards were used to demonstrate the changes in composition of the
      different developmental stages of the parasite as infection progressed. The
      prepatent period and time to peak infection was longer for field-infected lizards
      compared to those held under laboratory conditions. Infections in naturally
      infected field lizards had longer pre-patent periods and lower mean-peak
      parasitaemia than those in lizards that were uninfected at the time of
      experimental infection. The results are discussed in relation to the natural
      field-transmission dynamics of H. mariae in its lizard and tick hosts.

PMID- 11511005
TI  - Ultrastructure of the enteromonad flagellate Caviomonas mobilis.
AB  - Caviomonas mobilis was collected from the caecum of mice harbouring a controlled
      fauna. Phase contrast and immunofluorescence microscopy using an anti-tubulin
      antibody and electron microscopy demonstrated the presence of one basal body
      bearing a flagellum and a second barren basal body, both inserted in the face of
      two cup-like depressions in the nuclear surface, as in other
      enteromonad/diplomonad genera. Three microtubular fibres arise close to the main
      basal body: the first, composed of three microtubules cross-linked with a dense
      structure, lies within a groove above the nuclear surface; the second is oriented
      antero-dorsally and corresponds to the peristyle as observed by light microscopy;
      and the third is situated ventrally, below the proximal part of the recurrent
      flagellum, and corresponds to the funis. There is no mitochondrion, no Golgi
      body, the endoplasmic reticulum is reduced, there is no cytostome, the cell feeds
      by pinocytosis and phagocytosis and the division spindle is intranuclear. The
      cytological characters of Caviomonas are homologous to those of genera which
      comprise the enteromonad/diplomonad evolutionary lineage, as previously presumed.

PMID- 11511006
TI  - A description of Lecithocladium invasor n.sp. (Digenea: Hemiuridae) and the
      pathology associated with two species of Hemiuridae in acanthurid fish.
AB  - Lecithocladium invasor n.sp. is described from the oesophagus of Naso annulatus,
      N. tuberosus and N. vlamingii on the Great Barrier Reef, Australia. The worms
      penetrate the oesophageal mucosa and induce chronic transmural nodular
      granulomas, which expand the full thickness of the oesophageal wall and protrude
      both into the oesophageal lumen and from the serosal surface. We observed two
      major types of lesions: large ulcerated, active granulomas, consisting of a
      central cavity containing a single or multiple live worms; and many smaller
      chronic fibrous submucosal nodules. Small, identifiable but attenuated, worms and
      degenerate worm fragments were identified within some chronic nodules. Co
      infection of the posterior oesophagus of the same Naso species with
      Lecithocladium chingi was common. L. chingi is redescribed from N. annulatus, N.
      brevirostris, N. tuberosus and N. vlamingii. Unlike L. invasor n.sp., L. chingi
      was not associated with significant lesions. The different pathenogenicity of the
      two species in acanthurid fish is discussed.

PMID- 11511007
TI  - Effect of testosterone on Leishmania donovani infection of macrophages.

PMID- 11511009
TI  - Helminth fauna of the stoat (Mustela erminea Linneaus, 1758) and the weasel (M.
      nivalis Linnaeus, 1758) in Belorussian Polesie.
AB  - Helminthological examinations of 30 stoat and 31 weasel carcasses were carried
      out in Belorussian Polesie (southern part of Belarus, Brest and Gomel regions)
      between 1980 and 1999. The total rate of helminth infection of these animals was
      78.7%. A total of 23 stoats and 25 weasels were infected by helminths. The
      animals were hosts for 20 species of helminths.

PMID- 11511008
TI  - Detection of bancroftian filariasis in human blood samples from Sorsogon
      province, the Philippines by polymerase chain reaction.
AB  - The polymerase chain reaction (PCR) was used for diagnosing Wuchereria bancrofti
      infection in a small village in the province of Sorsogon, the Philippines. Of 54
      night-time blood samples collected, 4 (7.4%) were found to be microfilaremic as
      determined by combined direct blood film examination and membrane filtration of
      blood followed by blood film examination. However, utilization of the SspI PCR
      assay to detect repeated W. bancrofti DNA sequences in human blood doubled the
      number of microfilaremic individuals to 8 (13.0%). The results of this survey
      suggest that utilization of diagnostic tools based on microscopy could
      underestimate the true prevalence of W. bancrofti in the Philippines.

PMID- 11511010
TI  - Trustworthy?

PMID- 11511011
TI  - The GRIT: a quantitative measure of ulnar impaction syndrome.
AB  - The gripping rotatory impaction test (GRIT) is performed with a standard grip
      dynamometer and provides a quantitative measure for identifying ulnar impaction.
      The purpose of this study was to determine whether patients with unilateral ulnar
      impaction syndrome (UIS) have a GRIT ratio on the involved side greater than 1.0
      while the GRIT ratio on the uninvolved side is no different from 1.0. Twenty-four
      patients with unilateral UIS were tested with the GRIT on both the symptomatic,
      involved side and the asymptomatic, uninvolved side. The GRIT was performed with
      a standard grip dynamometer, and testing alternated between each patient's
      involved and uninvolved sides, with the wrist in the neutral, supinated, and
      pronated positions, in that order. The GRIT ratio on the involved side, at 1.37,
      was significantly greater than 1.0, while the GRIT ratio on the uninvolved side,
      at 1.03, was not significantly different from 1.0. The GRIT ratio is a
      quantitative measure that identifies UIS and can be used as an adjunct to imaging
      studies and qualitative clinical tests for UIS. The GRIT may also be helpful in
      determining which patients with UIS might benefit from surgical ulnar shortening.

PMID- 11511012
TI  - The coefficient of variation as a measure of sincerity of effort of grip
      strength, Part I: the statistical principle.
AB  - The coefficient of variation (CV) is a widely used measure of sincerity of effort
      of grip strength despite contradictory research findings and lack of empirical
      support in the literature. The purpose of this study was to investigate whether
      the CV is an appropriate measure of sincerity of effort. One hundred forty-six
      uninjured volunteers underwent a series of grip strength tests. The mean,
      standard deviation (SD), and CV of repeated strength trials were calculated, and
      paired comparisons were conducted between maximal and submaximal efforts. While
      the mean of maximal trials was significantly greater, there were no differences
      in SD between maximal and submaximal trials. Therefore, the increased CV
      associated with submaximal effort was an artifact of reduced torque rather than
      an indicator of a true increase in variability. Consequently, the CV is not an
      appropriate measure of sincerity of effort of grip strength.

PMID- 11511013
TI  - The coefficient of variation as a measure of sincerity of effort of grip
      strength, Part II: sensitivity and specificity.
AB  - The coefficient of variation (CV) is commonly used to detect sincerity of effort.
      The purpose of this study was to examine whether the CV possessed adequate
      sensitivity and specificity to effectively detect sincerity of effort of grip
      strength. One hundred forty-six uninjured volunteers underwent a series of grip
      strength tests. Sensitivity and specificity values were calculated for various CV
      cut-off values (between 2.5% and 22%) of the static grip test. The receiver
      operating characteristic (ROC) curves based on these values demonstrated the
      trade-offs between specificity and sensitivity. For example, the "traditional"
      15% cut-off value yielded poor sensitivity (0.55), whereas the 11% cut-off value
      yielded poor specificity (0.74). Selecting any cut-off value along the continuum
      did not provide adequate sensitivity or specificity for labeling an effort
      sincere or insincere. Although the CV differentiated between maximal and
      submaximal effort, it was not sensitive or specific enough to do so effectively.
      Thus, the CV should not be used to assess sincerity of effort of grip strength.

PMID- 11511014
TI  - Splinting and radial nerve palsy: a single-subject experiment.
AB  - This study examines which of three splint designs most effectively improved hand
      function in a patient with radial nerve palsy, and demonstrates the application
      of a single-subject experimental design. The static volar wrist cock-up splint
      (splint 1), dynamic tenodesis suspension splint (splint 2), and dorsal wrist cock
      up with dynamic finger extension splint (splint 3) were evaluated. Each splint
      was worn for 3 weeks, and hand function was assessed by means of standardized
      measures of function and disability. Statistical significance was calculated
      using the minimal level of detectable change (MDC) at the 95% confidence level.
      Only with splints 2 and 3 did a true change in function occur, compared with
      baseline scores (no splint). In addition, the patient completed all tasks while
      using splints 2 and 3 but did not complete three tasks while using splint 1. The
      hand therapists' goal is to fabricate a splint that improves function and that
      the patient will wear. Only splint 3 met these criteria. This experiment
      highlights the need to evaluate both the statistical and the clinical
      significance of treatment interventions.

PMID- 11511015
TI  - Results following trapeziometacarpal arthroplasty of the thumb.
AB  - A retrospective follow-up study was performed on patients with degenerative joint
      disease (DJD) who underwent trapeziometacarpal arthroplasty of the thumb with 3
      week immobilization and without the use of K-wire fixation. Pre- and post
      operative pain, activities of daily living (ADLs), grip strength, and pinch
      strength were compared. Data were collected on 25 hands in 23 patients, 7 hands
      with full trapezium resections and 18 with hemi-trapezium resections. The median
      age was 60 years, with a range of 39 to 73 years, and the median follow-up period
      was 1 year 11 months, with a range of 3 months to 11 years. Grip and pinch
      strength were measured pre- and postoperatively. Pain was assessed on a visual
      analog scale (VAS), and ADLs were assessed by means of a 15-item survey. Both
      pain and ADLs were evaluated postoperatively with recall of preoperative status.
      Following surgery, all thumbs were immobilized in a static splint for 3 weeks and
      then allowed progressive use. Median improvements in hemi-trapezium resections
      included grip, 22.5 lb; pinch, 4.7 lb; and ADLs, 33%. Pain was reduced a median
      of 7.0 cm on the VAS. Median improvements in full trapezium resection included
      grip, 29.5 lb; pinch, 0 lb; ADLs, 60%; and pain reduction, 8 cm on the VAS. This
      follow-up study suggests that satisfactory results can be achieved in pain
      reduction, strength, and ADLs with an immobilization period of only 3 weeks and
      without the use of K-wires following carpometacarpal (CMC) arthroplasty.

PMID- 11511016
TI  - A randomized prospective study to assess the efficacy of two cold-therapy
      treatments following carpal tunnel release.
AB  - A prospective randomized study was performed comparing the efficacy of controlled
      cold therapy (CCT) with the efficacy of ice therapy in the postoperative
      treatment of 72 patients with carpal tunnel syndrome. Immediately after surgery,
      patients applied either a temperature-controlled cooling blanket (CCT) or a
      standard ice pack over their surgical dressings. Pain was assessed by visual
      analog scale and swelling by wrist circumference preoperatively, immediately
      after surgery, and on postoperative day 3. Patients kept log books of daily
      treatment times. Narcotic use (of Vicodin ES) was determined by pill count at day
      3 and by daily log book recordings. Patients who used CCT showed significantly
      greater reduction in pain, edema (wrist circumference), and narcotic use at
      postoperative day 3 than did those using ice therapy. This study indicates that
      after carpal tunnel surgery, the use of CCT, compared with traditional ice
      therapy, provides patients with greater comfort and lessens the need for
      narcotics.

PMID- 11511017
TI  - A new device for flexor tendon injuries.
AB  - Managing the treatment of patients with zone II flexor tendon injuries for
      successful outcomes has always been a challenge for the hand therapist. Working
      closely with the patient to help ensure follow-through with the protocol is
      frequently necessary. If a patient is compliant, the therapist's concern then
      becomes one of "scar wars" (to use a phrase coined by Ken Flowers). Early active
      range of motion and tendon gliding are critical parts of most programs. This
      author has developed a new idea in conjunction with the Indiana Hand Center
      protocol.

PMID- 11511018
TI  - Sensitivity and specificity.

PMID- 11511019
TI  - Step one for asthma treatment: Beta2-agonists or inhaled corticosteroids?
AB  - Inhaled corticosteroids have proven effectiveness in chronic persistent asthma
      and are now recommended as first-line therapy in this condition. In contrast,
      long term preventative therapy is not currently considered necessary for patients
      with disease that is only mild and episodic. Recently, there has been growing
      interest in the possible benefits of using inhaled corticosteroids at an earlier
      stage in asthma, as soon as the condition is diagnosed. The concept of early
      intervention is supported by the recognition that airway inflammation is common
      to all grades of asthma, including early and mild disease. A number of studies
      have suggested that delayed introduction of inhaled corticosteroids in asthma can
      result in a poorer clinical response. The precise reason for this is unknown,
      although it may result from persistent uncontrolled inflammation leading to
      airway remodelling associated with airflow obstruction that is relatively
      resistant to therapy. There have also been suggestions that early intervention
      may alter the natural history of the disease, either to induce sustained
      remission or to prevent long term decline in lung function, but these effects
      have yet to be clearly established. On the basis of present knowledge, early
      intervention remains controversial, particularly in children. The Steroid
      Treatment As Regular Therapy (START) trial is a large, placebo-controlled,
      multicentre study that is currently comparing early and delayed use of inhaled
      corticosteroids in adults and children with newly diagnosed asthma. It is hoped
      that this study will resolve some of the present uncertainties, and lead to a
      better understanding of whether an early intervention strategy in asthma can be
      justified.

PMID- 11511020
TI  - Matrix metalloproteinases in the progression of heart failure: potential
      therapeutic implications.
AB  - Matrix metalloproteinases (MMPs) are a family of functionally related zinc
      containing enzymes that denature and degrade fibrillar collagens and other
      components of the extracellular matrix. Myocardial extracellular matrix
      remodelling and fibrosis regulated by MMPs are believed to be important
      contributors to the progression of heart failure. The role of MMPs in cardiac
      fibrosis and the progression of heart failure, along with the possibility of
      halting the progression of heart failure by modulating extracellular matrix
      remodelling are important issues under intense study. MMPs are increased in the
      failing hearts of both animal models and patients with heart failure. MMP
      inhibition may therefore modulate extracellular matrix remodelling and the
      progression of heart failure. It is a great advantage that various MMP inhibitors
      have been developed initially for the treatment of cancer, arthritis and other
      diseases believed to be associated with increased MMP activity. Several
      preclinical studies have shown that treatment of heart failure in animal models
      with MMP inhibitors results in less collagen matrix damage, favourable
      extracellular matrix remodelling, and improved cardiac structure and function.
      The results suggest that modulation of MMP activity can prevent myocardial
      dysfunction and the progression of heart failure through alterations in the
      remodelling process of extracellular matrix and the left ventricle. Although
      these promising results suggest potential benefits of MMP inhibition for human
      heart failure, no clinical data evaluating MMP inhibitors in heart failure have
      been reported. As the preclinical evidence continues to grow and the potential of
      MMP inhibition for the treatment of heart failure continues to unfold, MMP
      inhibition may prove to be an effective treatment for heart failure.

PMID- 11511022
TI  - Urinary tract infections in patients with spinal cord lesions: treatment and
      prevention.
AB  - Even though the mortality due to urinary tract complications has decreased
      dramatically during the last decades in individuals with spinal cord lesions
      (SCL), urinary tract infections (UTI) still cause significant morbidity in this
      population. Complicated UTI are caused by a much wider variety of organisms in
      individuals with SCL than in the general population and are often polymicrobial.
      Escherichia coli, Pseudomonas spp., Klebsiella spp., Proteus spp., Serratia spp.,
      Providencia spp., enterococci, and staphylococci are the most frequently isolated
      bacteria in urine specimens taken from individuals with SCL. There is no doubt
      that the greatest risk for complicated UTI in these individuals is the use of an
      indwelling catheter. Intermittent catheterisation during the rehabilitation phase
      has been shown to lower the rate of UTI, and virtually eliminate many of the
      complications associated with indwelling catheters. Persons with SCL should only
      be treated for bacteriuria if they have symptoms. Generally, it is advisable to
      use antibacterial agents with little or no impact on the normal flora. Single
      agent therapy - in accordance with antimicrobial susceptibility test - is
      preferred. We advise extending treatment to at least 5 days, and in those with
      reinfection or relapsing UTI, at least 7 to 14 days, depending on the severity of
      the infection. The diagnosis of structural and/or functional risk factors is
      essential in order to plan an optimal treatment for UTI in individuals with SCL,
      which should include treatment of simultaneously occurring predisposing factors.
      The treatment of structural risk factors follows general urological principles,
      aiming for sufficient outlet from the bladder with minimal residual urine and low
      pressure voiding. For prevention of UTI, general cleanliness and local hygiene
      should be encouraged. If the patient has a reinfection or relapsing symptomatic
      UTI, it is important to check for inadequately treated infection and
      complications, which need special attention, in particular residual urine and
      urinary stones. No reliable evidence exists of the effectiveness of cranberry
      juice and other cranberry products. Prophylactic antibacterials should only be
      used in patients with recurrent UTI where no underlying cause can be found and
      managed, and in particular if the upper urinary tract is dilated. Antibacterials
      should not be used for the prevention of UTI in individuals with SCL and
      indwelling catheters. However, the use of prophylactic antibacterials for
      individuals with SCL using intermittent catheterisation or other methods of
      bladder emptying is controversial.

PMID- 11511021
TI  - The clinical and cost considerations of bisphosphonates in preventing bone
      complications in patients with metastatic breast cancer or multiple myeloma.
AB  - The bisphosphonates are potent inhibitors of osteoclast-mediated bone resorption
      and are now the treatment of choice for the management of hypercalcaemia of
      malignancy. The incidences of hypercalcaemia and other skeletal complications
      (bone pain, pathological fracture) remain high despite apparent responses to
      systemic therapy, with particularly high event rates in women with advanced
      skeletal metastases of breast cancer. This review focuses on studies addressing
      the long-term efficacy of bisphosphonates to reduce skeletal complications in
      breast cancer (5 studies) and multiple myeloma (4 studies), with particular
      reference to controlled studies of sufficient magnitude and duration to allow
      confidence in the estimation of efficacy. Bearing in mind the limitations of
      differences in trial design and the lack of direct studies comparing drugs,
      adequate exposure to a bisphosphonate reduces the incidence of skeletal
      complication by 30 to 40% in both breast cancer and multiple myeloma. Oral
      clondronate and intravenous pamidronate have similar efficacy in both diseases,
      but the duration of efficacy may differ between drugs. Both agents have shown
      intriguing survival benefits in subgroups of patients. The numbers needed to
      treat (NNT) to prevent a skeletal complication during one year are lowest in
      metastatic skeletal disease in breast cancer (NNT < 8) but also compare very
      favourably with other disease for patients with recurrent nonskeletal breast
      cancer or multiple myeloma (NNTs 7 to 31 depending on the complication to be
      prevented). Treatment costs of both breast cancer and multiple myloma are driven
      by inpatient and outpatient hospital visits so that bisphosphonate regimens
      should be developed that reduce both. Further research is required to determine
      if subgroups of patients can be better identified that will derive particular
      benefit, or perhaps no benefit at all, from bisphosphonate therapy. It is not
      known whether more potent bisphosphonates will deliver greater clinical efficacy
      in the future.

PMID- 11511023
TI  - Changing approaches to asthma management in Australia: effects on asthma
      morbidity.
AB  - Asthma is an important public health issue in Australia and is responsible for
      significant morbidity and mortality in the community. Recognition of the impact
      of asthma on the health of Australians, and the apparent failure of new
      medications to reduce mortality and hospital admission rates resulted in a major
      review by the stakeholders in asthma care. This led to new approaches to asthma
      management based on strategic use of asthma medications and the development of
      the Asthma Management Plan (AMP). The AMP drew together current understanding of
      asthma to develop a simple stepwise approach to management that could be readily
      applied in patient management. The National Asthma Campaign (NAC), a coalition of
      the major stakeholders in asthma care, was launched in 1990 to lead the
      dissemination of the AMP. In association with other organisations interested in
      asthma care in Australia, the NAC has developed the AMP, and co-ordinated a
      decade of education and advocacy about asthma that targeted doctors, health
      professionals and the general public. These activities have been successful in
      raising awareness about asthma in the community. However, recent research, while
      demonstrating the continued uptake of written asthma action plans for asthma and
      decrease in use of inhaled bronchodilator medications, reported a decrease in use
      of preventive therapy by people with asthma. These activities have had a
      sustained impact on asthma-related health outcomes with mortality at the lowest
      level since 1960 and a decline in hospital readmission rates. This is useful
      information because there is sound evidence that the prevalence and possibly
      severity of asthma in children has increased. However, review of management in
      primary care and among people who present to emergency services with acute asthma
      suggest that many people continue to manage their asthma poorly. Continued
      education is needed to build on the progress that has been made. There are
      opportunities to do this through efforts to integrate general practitioners into
      the wider health system through the formation of Divisions of General Practice.
      Recognition of asthma as a health priority area at a national level will help to
      enhance and maintain awareness of the public health importance of asthma and
      facilitate the further development of the initiatives begun during the last
      decade or more.

PMID- 11511024
TI  - Management of AIDS-related non-Hodgkin's lymphomas.
AB  - The incidence of non-Hodgkin's lymphoma in individuals infected with HIV is
      approximately 60- to 100-fold increased over the general population. The majority
      of patients with AIDS-related lymphoma (ARL) present with stage III-IV disease
      and with B-symptoms. They often have multiple extranodal localisations, with a
      high incidence of central nervous system involvement. Histologically, most
      tumours are either diffuse large cell lymphomas or Burkitt lymphomas. Several
      factors, such as disrupted immune surveillance, Epstein-Barr virus infection,
      chronic antigenic stimulation, cytokine dysregulation and the acquisition of
      genetic lesions, are thought to contribute to the pathogenesis. Patients with ARL
      have a poor prognosis: overall survival ranges from 1.5 to 18 months. The most
      important adverse prognostic factors are poor performance status, a low CD4+ cell
      count and a history of opportunistic infections. Results of treatment with
      polychemotherapy compare unfavourably to results in patients without HIV
      infection. Since the advent of highly active antiretroviral therapy (HAART),
      there appears to be a decrease in the incidence of ARL. In addition, the use of
      HAART in combination with chemotherapy and the use of new treatment modalities
      may improve the outcome of this disease.

PMID- 11511025
TI  - Gemtuzumab ozogamicin.
AB  - Gemtuzumab ozogamicin is a humanised monoclonal IgG4 antibody, linked to a
      cytotoxic calicheamicin derivative. It effects cell necrosis by specifically
      targeting the CD33 antigen which is expressed on the surface of leukaemic cell
      blasts in more than 90% of patients with acute myeloid leukaemia (AML), but is
      not present on normal stem cells. Therapy with gemtuzumab ozogamicin (2 doses of
      9 mg/m2) in 3 noncomparative studies produced complete remission in 16% of adult
      patients with AML in first relapse, and complete remission with incomplete
      platelet recovery in an additional 13% of patients. Rates of remission did not
      differ between those aged less than 60 years and older than 60 years. Many
      patients were able to receive both doses of gemtuzumab ozogamicin therapy as
      outpatients. Survival duration was similar between those treated as outpatients
      and those requiring hospitalisation. About one-third of 11 children and
      adolescents treated with 2 doses of 9 mg/m2 gemtuzumab ozogamicin in a phase I
      study showed <5% bone marrow blasts after completion of therapy. The most
      commonly encountered adverse events in clinical trials with gemtuzumab ozogamicin
      were myelosuppression, increased levels of hepatic enzymes, infection, fever,
      bleeding, chills, nausea and vomiting and dyspnoea. No treatment-related renal
      failure or alopecia was reported.

PMID- 11511026
TI  - Inhaled mometasone furoate: a review of its use in adults and adolescents with
      persistent asthma.
AB  - Mometasone furoate is a corticosteroid with relatively high in vitro potency.
      Recent randomised, double-blind, multicentre trials have assessed the efficacy of
      mometasone furoate delivered by dry powder inhaler over 12 weeks in adults and
      adolescents with mild to severe persistent asthma. Mometasone furoate 200 microg
      twice daily or 400 microg once daily in the morning or 200 microg once daily in
      the evening improved lung function, asthma symptom scores and use of rescue
      medication to a significantly greater extent than placebo in patients who had
      previously received only short-acting inhaled beta2-adrenoceptor agonists alone
      as treatment in 3 trials (n = 195 to 306). In studies in 227 to 733 patients with
      mild to moderate asthma who were receiving ongoing treatment with inhaled
      corticosteroids prior to enrolment, mometasone furoate 100 to 400 microg twice
      daily was consistently better at improving the above indicators of asthma than
      placebo. Mometasone furoate 100 to 200 microg twice daily was as effective as
      beclomethasone dipropionate 200 microg twice daily or budesonide 400 microg twice
      daily and mometasone furoate 200 microg twice daily was as effective as
      fluticasone propionate 250 microg twice daily. Mometasone furoate 400 or 800
      microg twice daily was also consistently more effective than placebo in reducing
      oral corticosteroid dosages and improving lung function and asthma symptoms in
      132 patients with oral corticosteroid-dependent asthma. Once daily administration
      of mometasone furoate 400 microg appears to be as effective at improving
      indicators of asthma as twice daily administration of 200 microg. Patients
      receiving mometasone furoate < or =800 microg/day and recipients of placebo
      experienced a similar overall incidence of adverse events considered to be
      related to treatment. The most common of these events were oral candidiasis,
      headache, pharyngitis and dysphonia. Mometasone furoate 100 to 400 microg twice
      daily, beclomethasone dipropionate 200 microg twice daily, budesonide 400 microg
      twice daily or fluticasone propionate 250 microg twice daily were similarly
      tolerated. CONCLUSION: Inhaled mometasone furoate is well tolerated, with minimal
      systemic activity and is equally effective when administered as a divided dose or
      as a single daily dose. Use of the drug can result in a decrease in requirements
      for oral corticosteroids in patients with oral corticosteroid-dependent asthma
      and is as effective as other inhaled corticosteroids currently used in the
      treatment of mild to moderate persistent asthma. Thus mometasone furoate is
      suitable for the control of mild to severe persistent asthma in adults or
      adolescents.

PMID- 11511027
TI  - Aceclofenac: a reappraisal of its use in the management of pain and rheumatic
      disease.
AB  - Aceclofenac is an orally administered phenylacetic acid derivative with effects
      on a variety of inflammatory mediators. Through its analgesic and anti
      inflammatory properties, aceclofenac provides symptomatic relief in a variety of
      painful conditions. In patients with osteoarthritis of the knee, the drug
      decreases pain, reduces disease severity and improves the functional capacity of
      the knee to a similar extent to diclofenac, piroxicam and naproxen. Aceclofenac
      reduces joint inflammation, pain intensity and the duration of morning stiffness
      in patients with rheumatoid arthritis, and is similar in efficacy to ketoprofen,
      diclofenac, indomethacin and tenoxicam in these patients. The duration of morning
      stiffness and pain intensity are reduced, and spinal mobility improved, by
      aceclofenac in patients with ankylosing spondylitis, with improvements being
      similar to those observed with indomethacin, naproxen or tenoxicam. Aceclofenac
      is also effective in other painful conditions (e.g. dental and gynaecological).
      In contrast to some other NSAIDs, aceclofenac has shown stimulatory effects on
      cartilage matrix synthesis. Aceclofenac is well tolerated, with most adverse
      events being minor and reversible, and affecting mainly the GI system. Although
      the incidence of GI adverse events with aceclofenac was similar to those of
      comparator NSAIDs in individual clinical trials, withdrawal rates due to these
      events were significantly lower with aceclofenac than with ketoprofen and
      tenoxicam. Superior overall and/or GI tolerability of the drug relative to other
      NSAIDs has been indicated by a nonrandomised comparison with sustained release
      diclofenac in 10,142 patients, a meta-analysis of 13 comparisons with diclofenac,
      naproxen, piroxicam, indomethacin, tenoxicam or ketoprofen in 3574 patients, and
      preliminary details of a comparison with 10 other NSAIDs in 142,776 patients.
      Further analysis of the above meta-analytical data has indicated that costs
      incurred as a result of adverse event management are lower with aceclofenac than
      with a range of comparator NSAIDs. CONCLUSIONS: Trials of 2 to 6 months' duration
      have shown aceclofenac to be an effective agent in the management of pain and
      rheumatic disease. Data from in vitro studies indicate properties of particular
      interest with respect to cartilage matrix effects and selectivity for cyclo
      oxygenase-2. Aceclofenac is well tolerated, with encouraging reports of improved
      general and GI tolerability relative to other NSAIDs from a meta-analysis of
      double-blind trials and from large nonblind studies.

PMID- 11511028
TI  - A polymeric system for the intra-oral delivery of an anti-fungal agent.
AB  - Oral candidal infections are often persistent and intractable and thus the aim of
      this study was to develop a polymeric sustained release device to improve the
      topical treatment of these infections. A self curing system based on poly(ethyl
      methacrylate) and tetrahydrofurfuryl methacrylate (PEM/THFM) was used with
      chlorhexidine diacetate (CX) added at levels between 0 and 12% w/w. Water uptake
      by the device was assessed gravimetrically and CX release measured by UV
      spectrometry. Anti candidal activity was established by culturing azole sensitive
      and resistant strains of Candida albicans in the presence of the polymeric
      delivery device with and without CX. Candidal growth was measured by turbidimetry
      or surviving colony-forming unit (CFU) formation. There was an initial high
      release of CX over 24 h followed by a slow diffusion up to 7 days. CX inhibited
      candidal growth and survival markedly in vitro, with the test samples showing
      less than 0.5 x 10(-7) CFU/ml compared to controls (3-4 x 10(-7) CFU/ml). These
      results indicate the potential of a chlorhexidine containing PEM/THFM polymeric
      system in the treatment of persistent candidal infections.

PMID- 11511029
TI  - Isolation and morphological characterisation of UHMWPE wear debris generated in
      vitro.
AB  - Wear tests are generally carried out on materials used in prosthetic hip
      implants, in order to obtain a better understanding of the tribological processes
      involved and improve the quality control of joint prostheses, directed towards
      reducing the risk of implant failure of innovative prostheses. Ceramic femoral
      heads of mixed alumina-zirconia oxides as well as zirconia and alumina single
      oxide heads were tested against UHMWPE acetabular cups in a hip joint simulator.
      Polyethylene cups and ceramic femoral heads were mounted in a simulator apparatus
      moving according to a sinusoidal function, under load and in the presence of
      bovine calf serum as lubricant. Wear particles were isolated from the bovine calf
      serum collected during the wear tests. An easy to follow method was used to
      separate the wear particles from the lubricant. Chemical digestive methods were
      used to separate the wear particles from the lubricant and the isolated particles
      were studied using scanning electron microscopy. The morphologies of the
      polyethylene debris showed considerable differences, both in size and shape of
      the particles, as a function of the coupled head material.

PMID- 11511030
TI  - Immunohistochemical characterization of axonal sprouting and reactive tissue
      changes after long-term implantation of a polyimide sieve electrode to the
      transected adult rat sciatic nerve.
AB  - The development of artificial microstructures suited for interfacing of
      peripheral nerves is not only relevant for basic neurophysiological research but
      also for future prosthetic approaches. Aim of the present study was to provide a
      detailed analysis of axonal sprouting and reactive tissue changes after
      implantation of a flexible sieve electrode to the proximal stump of the adult rat
      sciatic nerve. We report here that massive neurite growth after implantation,
      steadily increasing over a period of 11 months, was observed. Parallel to this
      increase was the expression of myelin markers like Po, whereas non-myelin-forming
      Schwann cells did not change. Compared to five weeks post-implantation. where
      both Schwann-cell phenotypes were intermingled with each other, non-myelin
      forming Schwann cells occupied a peripheral position in each microfascicle after
      11 months. After an initial increase, hematogenous macrophages were down
      regulated in number but maintained close contact with the implant. However, at no
      time were signs of its degradation observed. It is concluded that the introduced
      flexible polyimide electrode is suitable for contacting peripheral nerves since
      it permits substantial neurite growth and offers excellent long-term stability.

PMID- 11511031
TI  - Thiolated polymers--thiomers: development and in vitro evaluation of chitosan
      thioglycolic acid conjugates.
AB  - The aim of this study was to improve mucoadhesive properties of chitosan by the
      covalent attachment of thiol moieties to this cationic polymer. Mediated by a
      carbodiimide, thioglycolic acid (TGA) was covalently attached to chitosan. This
      was achieved by the formation of amide bonds between the primary amino groups of
      the polymer and the carboxylic acid group of TGA. Dependent on the pH-value and
      the weight ratio of polymer to TGA during the coupling reaction the resulting
      thiolated polymers, the so-called thiomers, displayed 6.58, 9.88, 27.44, and
      38.23 micromole thiol groups per gram polymer. Tensile studies carried out with
      these chitosan-TGA conjugates on freshly excised porcine intestinal mucosa
      demonstrated a 6.3-, 8.6-, 8.9-, and 10.3-fold increase in the total work of
      adhesion (TWA) compared to the unmodified polymer, respectively. In contrast, the
      combination of chitosan and free unconjugated TGA showed almost no mucoadhesion.
      These data were in good correlation with further results obtained by another
      mucoadhesion test demonstrating a prolonged residence time of thiolated chitosan
      on porcine mucosa. The swelling behavior of all conjugates was thereby exactly in
      the same range as for an unmodified polymer pretreated in the same way.
      Furthermore, it could be shown that chitosan-TGA conjugates are still
      biodegradable by the glycosidase lysozyme. According to these results. chitosan
      TGA conjugates represent a promising tool for the development of mucoadhesive
      drug delivery systems.

PMID- 11511032
TI  - Structure of dental glass-ionomer cements by confocal fluorescence microscopy and
      stereomicroscopy.
AB  - The microstructure of four cements, setting by different mechanisms (acid-base,
      dual cure, triple cure), was studied. The porosity of unpolymerized materials was
      detected by stereomicroscopy. After polymerization and storage in water or lactic
      acid solution, the porosity, filler distribution and gel layer, which was formed
      at the filler/matrix interface of polymerized materials, were examined by
      confocal laser microscopy. For this purpose, the specimens were treated with
      fluorescent dye solution before the test. The results showed that hydrolytic
      degradation (pH 7) mainly involved the resin matrix, and the acid erosion (pH
      3.5) involved the gel layer too. As regards the filler, materials with different
      setting mechanism released the glass particles in different times. The loss of
      the filler particles occurred quicker in acid-base setting cements, and slower in
      triple-cured material.

PMID- 11511033
TI  - Linkage of chondroitin-sulfate to type I collagen scaffolds stimulates the
      bioactivity of seeded chondrocytes in vitro.
AB  - An increasing amount of interest is focused on the potential use of tissue
      engineered articular cartilage implants, for repair of defects in the joint
      surface. In this perspective, various biodegradable scaffolds have been evaluated
      as a vehicle to deliver chondrocytes into a cartilage defect. This cell-matrix
      implant should eventually promote regeneration of the traumatized articular joint
      surface with hyaline cartilage. Successful regeneration can only be achieved with
      such a tissue-engineered cartilage implant if the seeded cells reveal an
      appropriate proliferation rate in the biodegradable scaffold together with the
      production of a new cartilage-specific extracellular matrix. These metabolic
      parameters can be influenced by the biochemical composition of a cell-delivery
      scaffold. Further elucidation of specific cell-matrix interactions is important
      to define the optimal biochemical composition of a cell-delivery vehicle for
      cartilage repair. In this in vitro study, we investigated the effect of the
      presence of cartilage-specific glycosaminoglycans in a type I collagen scaffold
      on the metabolic activity of seeded chondrocytes. Isolated bovine chondrocytes
      were cultured in porous type I collagen matrices in the presence and absence of
      covalently attached chondroitin sulfate (CS) up to 14 days. CS did indeed
      influence the bioactivity of the seeded chondrocytes. Cell proliferation and the
      total amount of proteoglycans retained in the matrix, were significantly higher
      (p < 0.001) in type I collagen scaffolds with CS. Light microscopy showed the
      formation of a more dense cartilaginous layer at the matrix periphery. Scanning
      electron microscopy revealed an almost complete surfacing of the initially porous
      surface of both matrices. Histology and reverse transcriptase PCR for various
      proteoglycan subtypes suggested a good preservation of the chondrocytic phenotype
      of the seeded cells during culture. The stimulatory potential of CS on both the
      cell-proliferation and matrix retention, turns this GAG into an interesting
      biochemical component of a cell-delivery scaffold for use in tissue-engineering
      articular cartilage.

PMID- 11511034
TI  - Degradation of poly(D,L)lactide implants with or without addition of
      calciumphosphates in vivo.
AB  - The study was aimed at examining the in vivo degradation of pure poly(D,L)lactide
      (PDLLA) or PDLLA with an admixture of calciumphosphates. One rod (20 x 3 x 2 mm)
      and one cube (3 x 2 x 2 mm) of pure PDLLA, PDLLA with tricalciumphosphate (PDLLA
      + TCP) or PDLLA with calciumhydrogenphosphate (PDLLA + CHP), respectively, were
      implanted into the dorsal muscles of 50 male Wistar Albino rats. After definite
      intervals (from 2nd to 72nd week), pH measurements were performed in the
      environment of the implants. Afterwards, the cubes with their surrounding tissues
      were excised for histological examinations, measurements of the outer dimensions
      and mechanical analyses of the explanted rods were performed. No drop of more
      than 0.1 pH units was detectable in the tissue surrounding any type of implants.
      No advantageous effect of the calciumphosphates could be proved. A mild foreign
      body reaction could be observed around PDLLA implants. After 72 weeks, pure PDLLA
      had been totally resorbed from the extracellular space, the degradation of
      calciumphosphate-enriched PDLLA was still in progress. A large amount of
      inflammations occurred in the tissues surrounding PDLLA with an admixture of
      slowly degrading TCP or CHP, leading to two abscesses and four fistulas at PDLLA
      + TCP, and two abscesses and three fistulas at PDLLA + CHP implantation site.
      Bending strength of pure PDLLA was constant up to the 4th week post-implantation
      and reduced to 60% of the initial value up to the 12th week. No traces of
      crystallinity could be observed during the degradation of PDLLA. As a conclusion
      of the study, complete resorption from the extracellular space and tissue
      tolerance of pure PDLLA is proved. An admixture of small calciumphosphate
      particles is not suitable to improve the biocompatibility of PDLLA but leads to a
      decrease in the mechanical characteristics.

PMID- 11511035
TI  - Water-soluble covalent conjugates of bovine serum albumin with anionic poly(N
      isopropyl-acrylamide) and their immunogenicity.
AB  - We have conjugated bovine serum albumin (BSA) to poly(N-isopropylacrylamide-co
      acrylic acid) (poly(NIPAAm-AA)) by using water-soluble carbodiimide, and the
      effects of the bulk mass ratio of protein to polymer (r) on the formation of
      polymer-protein conjugates have been studied. HPLC, electrophoresis, viscosimetry
      and fluorescence spectroscopy suggest that the mode of covalent binding of BSA to
      poly(NIPAAm-AA) depends upon the weight concentration ratio (r) of BSA to
      poly(NIPAAm-AA). At r < or = 1, free poly(NIPAAm-AA) molecules coexist with
      conjugate, and when r reaches 1 the amount of free polymer is too small to be
      observed. It is shown that depending on the ratio r, two types of conjugate
      particles were formed: at r < 1, the protein molecules in the structure of
      conjugate particles are densely covered as a shell by polymer chain and
      practically "fenced off" from water environment; at r > 1 the conjugate-forming
      particles possess more friable structures in which protein molecules are
      practically exposed to the solvent. The complex formation involving electrostatic
      interactions between BSA and carbodiimide activated polymer are proposed as the
      driving force for the covalent binding of BSA to polymer macromolecules. The coil
      globule transition of macromolecules in low and thermally induced precipitation
      in more concentrated solutions of bioconjugates was observed. The immunogenic
      properties of covalent conjugates of CP-BSA were investigated and the temperature
      modulated solubility-immunogenicity alterations was analyzed. A single
      immunization of mice with conjugates at the thermally precipitating concentration
      without an adjuvant evoked increased specific immune response to BSA, which
      practically did not depend on the initial conjugation ratio of components. Such a
      modulated system is attractive for application as a novel immunogenic system in
      vaccine technology.

PMID- 11511036
TI  - The migration of cells from the ruptured human anterior cruciate ligament into
      collagen-glycosaminoglycan regeneration templates in vitro.
AB  - Guided tissue regeneration of the ruptured anterior cruciate ligament (ACL)
      offers the potential benefits of retaining the complex footprints of the ACL and
      the proprioceptive nerve fibers of the tissue. For this approach to be
      successful, ACL cells must retain the ability to migrate into an adjacent
      regeneration template, or scaffold, after ligament rupture. Ruptured ACLs were
      obtained from the knees of four men, ages 25-35, at the time of ACL
      reconstruction. Explants of ACL tissue were taken from three locations along the
      longitudinal axis of the remnant: the rupture site, the middle of the remnant,
      and far from the rupture site. These three areas have been found to be distinct
      histologically, with the region far from the rupture site having a histologic
      appearance similar to the intact ligament. Explants from each area were cultured
      in conventional tissue culture dishes (2-D culture) and on porous collagen
      glycosaminoglycan (CG) scaffolds. Two-dimensional outgrowth was measured 3 times
      a week, and the 3-D explant/scaffold constructs were examined at 1, 2, 3 and 4
      weeks to assess outgrowth of cells into the scaffold. The cell number density and
      expression of a-smooth muscle actin (SMA) were determined at each time point. The
      decrease in the diameter of the scaffolds and non-seeded controls were determined
      as a function of time in culture. The outgrowth of cells onto the tissue culture
      dishes was observed to begin as early as 3 days and as late as 21 days, with
      outgrowth first detected at an average of 6.8 +/- 2.0 days after explantation. In
      general, there was a larger area of outgrowth at the 2-week time point from
      explants with higher cell number density and higher blood vessel density. The 2
      week area of outgrowth also correlated with the percentage of SMA-positive cells
      in the explant. In the experimental constructs with CG scaffolds, fibroblasts
      were noted to migrate from the human ACL explants into the templates at the
      earliest time point recorded (I week). The migration and proliferation of cells
      from the explants in the CG matrices resulted in an increase in the cell density
      in the scaffolds with time. There was a significant effect of the location from
      which the explant was taken on cell density in the scaffold, with a higher
      density of cells migrating from the explants from the rupture site of the ACL
      specimens. The percentage of cells staining positive for the SMA isoform varied
      from 0 to 50% of cells in the scaffold. Scaffolds co-cultured with explants
      showed a reduction in diameter that was significantly affected by time in culture
      and the location in the ACL from which the explant was taken. The percentage
      contraction attributed to the cells was 15% at 2 weeks, and increased to 27% for
      the injury-zone explant at 4 weeks. There was a significant correlation of the
      cell-mediated contraction of the matrices at 4 weeks with the cell density in the
      scaffolds, but not with the number of SMA-positive cells in the scaffolds. These
      data demonstrate that cells in the human ACL retain their ability to migrate into
      an adjacent CG scaffold in vitro, weeks after complete rupture. Moreover, the ACL
      derived cells can express a contractile actin isoform and can contract a CG
      analog of extracellular matrix.

PMID- 11511037
TI  - Von Willebrand factor, a key protein in the exposure of CD62P on platelets.
AB  - When a biomaterial is introduced into the body water, electrolytes, and proteins
      adsorb to the surface. Platelets are then the first cells to interact with the
      surface adsorbed protein layer. We have studied the role of von Willebrand factor
      (vWF) for platelet-protein interaction by measuring different platelet responses
      to protein- and plasma-coated hydrophobic glass surfaces. A high exposure of
      CD62P on the platelet surface was seen after 10 min of incubation on platelets
      interacting with vWF and normal plasma-coated surfaces (79 and 67%,
      respectively). On the surfaces coated with albumin and factor VIII deficient
      plasma, the exposure was low (11 and 27%, respectively). A higher formation of
      filipodial extensions on the platelets was seen on the surfaces coated with vWF
      and normal plasma than on the surfaces coated with albumin or factor VIII
      deficient plasma. No significant differences were seen between the surfaces
      regarding the platelet release of PF4, ATP, or phospholipids. As shown by these
      results, vWF is a specific regulator of the exposure of CD62P by platelets and
      hence important for the interaction between platelets and later arriving
      neutrophils at biomaterial surfaces.

PMID- 11511038
TI  - Isoprene-styrene copolymer elastomer and tetrahydrofurfuryl methacrylate mixtures
      for soft prosthetic applications.
AB  - Novel elastomer/methacrylate systems have been developed for potential soft
      prosthetic applications. Mixtures of varying compositions of an isoprene-styrene
      copolymer elastomer and tetrahydrofurfuryl methacrylate (SIS/THFMA) formed one
      gel systems and were heat cured with a peroxide initiator. The blends were
      characterised in terms of sorption in deionised water and simulated body fluids
      (SBF), tensile properties and viscoelastic parameters of storage modulus and tan
      delta, as well as glass transition temperatures using dynamic mechanical analysis
      (DMA). DMA data gave two distinct peaks in tan delta, a lower temperature
      transition due to the isoprene phase in SIS and one at high temperature thought
      to be a combination of THFMA and the styrene phase in SIS. The tensile data
      showed a clear phase inversion within the mid range compositions changing from
      plastic to elastomeric behaviour. The sorption studies in deionised water showed
      a two stage uptake with an initial Fickian region that was linear to t 1/2
      followed by a droplet growth/clustering system. The slope of the linear region
      was dependent on the composition ratio. The extent of overall uptake was
      osmotically dependent as all materials equilibrated at a much lower uptake in
      SBF. The diffusion coefficients were found to be concentration dependent.

PMID- 11511039
TI  - Transplantation of chondrocytes seeded on a hyaluronan derivative (hyaff-11) into
      cartilage defects in rabbits.
AB  - Different methods have been used to improve chondrocyte transplantation for the
      repair of articular cartilage defects. Several groups of biomaterials have been
      proposed as support for in vitro cell growth and for in vivo implantation. Here.
      we describe a new approach investigating the healing of rabbit cartilage by means
      of autologous chondrocytes seeded on a hyaluronan derivative referred to as Hyaff
      11. Full thickness defects were created bilaterally in the weight-bearing surface
      of the medial femoral condyle of both femora of New Zealand male rabbits. The
      wounds were then repaired using both chondrocytes seeded on the biomaterial and
      biomaterial alone. Controls were similarly treated but received either no
      treatment or implants of the delivery substance. Histologic samples from in and
      around the defect sites were examined 1, 3 and 6 months after surgery and were
      scored from 0 to 16. Statistically significant differences in the quality of the
      regenerated tissue were found between the grafts carried out with biomaterial
      carrying chondrocyte cells compared to the biomaterial alone or controls. This
      study demonstrates the efficacy of this hyaluronan-based scaffold for autologous
      chondrocytes transplantation.

PMID- 11511040
TI  - Structural alterations of adhesion mediating components in cells cultured on poly
      beta-hydroxy butyric acid.
AB  - Polymers may serve as a biodegradable material in tissue engineering. To assess
      the biocompatibility of poly-beta-hydroxy butyric acid (PHB), we studied the
      structural organization of cellular molecules involved in adhesion using
      osteoblastic and epithelial cell lines. On PHB, both cell lines revealed a
      rounded cell shape due to reduced spreading. The filamentous organization of the
      actin cytoskeleton was impaired. In double immunofluorescence analyses we
      demostrated that the colocalization of the fibronectin fibrils with the actin
      filaments was lost in cultures on PHB. Similarly, collagen II distribution was
      altered, whereas the organization of collagen I was not obviously affected.
      Further evidence for impaired structural organization was obtained for the beta1
      integrin receptor and vinculin which mediate the interaction of the cytoskeleton
      with the extracellular matrix. In confluent epithelial cells, the tight junction
      protein ZO-1 showed a larger lateral extension in the cell-cell contacts when
      cells were grown on PHB. Because structural organization of components which
      mediate cell-matrix and cell-cell adhesion controls cell physiology these
      parameters could be a sensitive indicator for the biocompatibility of implant
      materials.

PMID- 11511044
TI  - Interfacial rheological properties of adsorbed protein layers and surfactants: a
      review.
AB  - Proteins and low molecular weight (LMW) surfactants are widely used for the
      physical stabilisation of many emulsions and foam based food products. The
      formation and stabilisation of these emulsions and foams depend strongly on the
      interfacial properties of the proteins and the LMW surfactants. Therefore these
      properties have been studied extensively. In this review an overview is given of
      interfacial properties of proteins at a mesoscopic scale and the effect of LMW
      surfactants (emulsifiers) on them. Properties addressed are the adsorbed amount,
      surface tension (reduction), network formation at interfaces and possible
      conformational changes during and after adsorption. Special attention is given to
      interfacial rheological behaviour of proteins at expanding and compressing
      interfaces, which simulate the behaviour in real emulsions and foams. It will be
      illustrated that information on interfacial rheological properties, protein
      conformation and interactions between adsorbed molecules can be obtained by
      changing experimental conditions. The relation between interfacial rheology and
      emulsion and foam stabilisation is subsequently addressed. It is concluded that
      there is a need for new measuring devices that monitor several interfacial
      properties on a mesoscopic and microscopic scale at the same time, and for
      physical models describing the various processes of importance for proteins. Real
      progress will only be possible if both are combined in an innovative way.

PMID- 11511041
TI  - Binding of a model regulator of complement activation (RCA) to a biomaterial
      surface: surface-bound factor H inhibits complement activation.
AB  - The complement system is an important inflammatory mediator during procedures
      such as cardiopulmonary bypass and hemodialysis when blood is exposed to large
      areas of biomaterial surface. This contact between blood and the biomaterials of
      implants and extracorporeal circuits leads to an inflammatory response mediated
      by the complement system. The aim of this study was to assess the ability of a
      complement regulator (factor H) immobilised on a biomaterial surface to inhibit
      complement cascade mediated inflammatory responses. The cross-linker N
      succinimidyl 3-(2-pyridyldithio) propionate was used to immobilise factor H on a
      model biomaterial surface without affecting the biological activity of the
      inhibitor. Binding of factor H was then characterised using quartz crystal
      microbalance-dissipation (QCM-D) and enzyme immunoassays for products of
      complement activation: bound C3 fragments and soluble C3a, sC5b-9, and C1s-C1INA.
      Immobilised factor H reduced the amount C3 fragments deposited on the biomaterial
      surface after incubation with serum, plasma. or whole blood. In addition, lower
      levels of soluble C3a and sC5b-9 were generated after incubation with whole
      blood. In summary, we have demonstrated that complement activation on a highly
      activating model surface can be inhibited by immobilised factor H and have
      defined prerequisites for the preparation of future biomaterial surfaces with
      immobilised regulators of complement activation.

PMID- 11511046
TI  - The dilemma of "to-be or not-to-be": needs and expectations of the Taiwanese
      cadaveric organ donor families during the pre-donation transition.
AB  - There has been little study of the Chinese cadaveric donor family's decisions to
      donate organs within the Chinese cultural framework. A convenience sample of 25
      cadaveric donor family members (12 men, 13 women) who gave their consent to
      donation at National Taiwan University Hospital agreed to participate in this
      study and completed in-depth interviews. Data were analyzed by a three-steps
      within-method qualitative triangulation method. The factors influencing the donor
      family's decisions to donate organs, the needs of donor families, and their
      expectations of health care providers during the pre-donation transition--the
      critical period of time between signing a donation and consent to organ
      harvesting--were examined. The background context and a conceptual framework were
      further developed to discuss and depict this phenomenon. This project aims to
      broaden the horizon on organ donation and contribute to the understanding of some
      of the psychodynamic issues in the Chinese family in Taiwan.

PMID- 11511047
TI  - Ethical issues and the importance of consensus for the intensive care team.
AB  - This paper draws upon an empirical study and combines moral philosophical
      insights and sociological analysis to shed light on the ethical issues in
      intensive care. It is argued that moral philosophical debate often leaves aside
      the social context in which ethical decisions are taken and carried through. In
      order to gain an understanding of how intensive care is accomplished and
      specifically how ethical issues are handled, the study focused primarily on
      nurses' accounts of and views on the practices which form the everyday work of
      intensive care. A qualitative approach was adopted involving theoretical sampling
      and the constant comparative method of analysis. The paper argues that the most
      difficult ethical issue in intensive care, namely the withholding or withdrawal
      of treatment, is an area in which nursing and medical perspectives are often at
      odds. However, when the social context of clinical practice is taken into
      account, this paper argues. there is common ground between the two professions.
      It was found that the period during which the decision to withdraw treatment is
      being made, the members of the intensive care team closest to the bedside,
      nursing and medical staff. become impatient for some resolution of the situation.
      The differences of opinion which arise over the decision to withdraw are not
      simply to do with the way in which the situation is experienced by each
      professional group, proximity to the patient had a part to play in shaping their
      views rather than, as it is sometimes presumed. a simple rift between medicine
      and nursing. The data suggest that intensive care has to be a team effort. Even
      though there is no legal requirement for nurses to agree with the ICU decisions,
      there seems to be a strong desire within the intensive care team that moral
      consensus should be achieved in the interests of good patient care. Intensive
      care relies on the integrity of the team and the unfailing functioning of
      teamwork. Consequently, achieving this, it seems, is more important than other
      temporary lapses in interprofessional relations and disagreements over treatment
      in individual cases. Consensus is important and its achievement is a central, day
      to day working arrangement for insuring the solidarity of the team.

PMID- 11511048
TI  - Decisions about treatment: interpretations of two measures of control by women
      having a hysterectomy.
AB  - A number of authors have developed sets of role descriptions that have been used
      to classify patients' roles in decisions about their health care as either
      active, collaborative or passive. We explored the validity of two such measures.
      Twenty women who had recently had a hysterectomy described their experiences of
      treatment decision-making in their own words and picked role descriptions from
      the Control Preferences Scale (Degner, Sloan, J. Clin. Epidemiol. 45 (1992) 941)
      and Patient Preferences for Control measure (Bradley et al.. Fam. Med. 28 (1996)
      496), both phrased in the past tense to assess roles played. The women explained
      why they had picked particular role descriptions. We compared the women's
      selections from the two measures and considered the relationship between their
      narrative descriptions and the role descriptors they picked. Several women found
      it hard to find an appropriate role description among those they were offered.
      Some picked apparently conflicting statements from the two measures. The role
      classifications that would be made on the basis of the women's chosen role
      descriptions did not always seem appropriate when compared with their narrative
      descriptions of how treatment decisions were reached. Women gave a range of
      explanations for choosing the role descriptors that they did, and some women who
      picked different role descriptions gave similar explanations for doing so. These
      findings suggest that there are problems with the validity of some currently used
      measures of patients' participation in health care decision-making. Researchers
      need to pay more attention to the key features of participation in decision
      making and develop measures that can distinguish between these.

PMID- 11511049
TI  - Post-modernity and post-traumatic stress disorder.
AB  - The after effects of trauma have assumed a central role in the discourses of
      psychiatry and psychology in recent years. Most commentators have looked for an
      explanation of this explosion of interest in trauma, to developments within
      psychiatry and psychology. However, it is argued here that important cultural
      changes in the Western world have produced the conditions in which this interest
      has come about. The advent of post-modernity has witnessed an undermining of
      social stability and coherence and a systematic weakening of those cultural
      institutions which provide meaning and order for individuals. Following trauma,
      the development of the characteristic symptoms of post-traumatic stress disorder
      (PTSD) is currently understood to arise from a breakdown of meaning within the
      victim's world. I seek to establish an association between PTSD and the culture
      of post-modernity. I argue that this connection has important implications with
      regard to our understanding of the relationship between trauma and culture more
      generally.

PMID- 11511050
TI  - Understanding the role of opinion leaders in improving clinical effectiveness.
AB  - We present findings from evaluations of two government-funded initiatives
      exploring the transfer of research evidence into clinical practice--the PACE
      Programme (Promoting Action on Clinical Effectiveness), and the Welsh Clinical
      Effectiveness Initiative National Demonstration Projects. We situate the findings
      within the context of available research evidence from healthcare and other
      settings on the role of opinion leaders or product champions in innovation and
      change--evidence which leaves a number of problems and unanswered questions. A
      major concern is the difficulty of achieving a single replicable description of
      what opinion leaders are and what they do--subjective understandings of their
      role differ from one setting to another, and we identify a range of very
      different types of opinion leadership. What makes someone a credible and
      influential authority is derived not just from their own personality and skills
      and the dynamic of their relationship with other individuals, but also from other
      context-specific factors. We examine the question of expert versus peer opinion
      leaders, and the potential for these different categories to be more or less
      influential at different stages in the innovation process. An often neglected
      area is the impact of opinion leaders who are ambivalent or hostile to an
      innovation. Finally, we note that the interaction between individual opinion
      leaders and the collective process of negotiating a change and reorienting
      professional norms remains poorly understood. This raises a number of
      methodological concerns which need to be considered in further research in this
      area.

PMID- 11511051
TI  - Marital fertility in Lebanon: a study based on the population and housing survey.
AB  - This study tested the general economic theory of fertility within the contextual
      setting of the Lebanese society, by using the 1996 Population and Housing
      Database Survey. The theory argues that the household's demand for a child is
      closely related to different services and utilities ascribed to that child. It
      also claims that fertility as such is income-inelastic, but becomes positively
      associated with the household's income when the notion of child-quality is added
      to the model. Findings confirm the baseline inverse association between an index
      of the household's socioeconomic status (HSES) and the cumulative fertility
      level. However, when women's education was added to the model, an interaction was
      observed whereby the illiterate subgroup--unlike the educated--was at higher risk
      of having a large number of children with improvement in their economic
      conditions. A similar interaction was found between women's and husband's
      education. It was concluded that in response to higher socioeconomic status,
      illiterate women end up supplying an excess number of children, an effect
      mediated by the shortening of lactation period, which is in turn triggered by a
      higher access to breast milk substitutes. On the other hand, their educated
      husbands demand 'child quantity' since this educational gap grants them more
      power to decide their family size. In contrast, educated women demand child
      'quality' as they expect both material and opportunity costs of having a child to
      coincide with the norms and values of their social class. Their lower supply of
      births with increased economic well-being is primarily attributed to a higher use
      of modern contraceptive methods. Other factors investigated in this study
      included the potential effect of family structure on fertility, and control was
      done on a number of other sociocultural and demographic variables, such as
      women's work status, husband's occupation, age at marriage and area of residence.

PMID- 11511052
TI  - Health and variation in deprivation: commentary on Boyle et al.

PMID- 11511053
TI  - Understanding the role of contextual influences on local health-care decision
      making: case study results from Ontario, Canada.
AB  - Approaches to involving the public in local health care decision making processes
      (and analyses of these approaches) have tended to treat participation and publics
      uniformly in search of the ideal method of involving the public or providing the
      same opportunities for public participation regardless of differing socio
      economic, cultural, insitutional or political contexts within which decisions are
      made. Less attention has been given to the potential for various contextual
      factors to influence both the methods employed and the outcomes of such community
      decision-making processes. The paper explores the role that context (three sets
      of contextual influences more specifically) plays in shaping community decision
      making processes. Results from case studies of public participation in local
      health-care decision making in four geographic communities in Ontario are
      presented. During the study period, two of these communities were actively
      involved in health services restructuring processes while one had recently
      completed its process and the fourth had not yet engaged in one. Several themes
      emerge from the case studies regarding the identification and role of contextual
      influences in differentially shaping participation in local health care decision
      making. These include the propensity for communities with different social and
      structural attributes to engage in different "styles" of participation; the
      importance attached to "community values" in shaping both the qualitative and
      quantitative aspects of participation: the role of health councils, local
      government and inter-organizational collaboration as participation "enablers";
      and the politicization of participation that occurs around contentious issues
      such as hospital closures.

PMID- 11511054
TI  - Do area-level population change, deprivation and variations in deprivation affect
      individual-level self-reported limiting long-term illness?
AB  - A previous study showed that variations in deprivation within small localities in
      England and Wales influenced the rates of self-reported limiting long-term
      illness, controlling for overall levels of deprivation. These results suggest
      that while morbidity is related to overall levels of material deprivation, the
      distribution of resources within small areas have a significant effect on health
      outcomes. However, it is possible that these area effects become redundant once
      individual-level characteristics are accounted for. This analysis examines
      whether area-level deprivation and variations in deprivation are significant
      indicators of individual-level limiting long-term illness, once individual
      characteristics have been accounted for.

PMID- 11511055
TI  - On the methodological, theoretical and philosophical context of health
      inequalities research: a critique.
AB  - The integration of survey data with psycho-social theories is an important and
      emerging theme within the field of health inequalities research. This paper
      critically examines this approach arguing that the respective models of health
      inequality which these approaches promote, the related concepts of 'social
      cohesion' and 'social capital' suffer from serious methodological, theoretical
      and philosophical flaws. The critique draws particular attention to the
      limitations of survey-derived data and the dangers of using such data to develop
      complex social explanations for health inequalities. The paper discusses wider
      epistemological issues which emerge from the critique addressing the fundamental
      but neglected question of 'what is inequality'? The paper concludes by
      introducing a structure for questions regarding health inequalities emphasising
      the need for those question to be attached to real communities.

PMID- 11511056
TI  - Does class matter? SES and psychosocial health among Hungarian adolescents.
AB  - Previous research finds a significant relationship between socioeconomic
      inequalities and health status: individuals with lower income, education, and
      occupational prestige have and report more health problems. Interestingly, this
      relationship is not consistent across the life cycle: health differences among
      adolescents across socioeconomic groups are not as clearly defined. Using data (n
      = 1,039) on adolescents from southern Hungary, we examine the role of
      socioeconomic differences in predicting psychosocial health. We argue that this
      investigation is of particular importance in a post-communist system where the
      general perception of SES is undergoing significant transformation. Findings show
      that classical' SES (socioeconomic status) indicators (manual/nonmanual
      occupational status) were not significant predictors of psychosocial health in
      this sample of Hungarian adolescents. While parents' employment status as a
      'objective' SES indicator had limited effect, SES self-assessment, as a
      subjective SES variable, proved to be a strong predictor of adolescents'
      psychosocial health. We discuss the implications of these findings for the
      broader SES-health literature with specific attention paid to the impact these
      relationships may have for adolescent and young adult development in a post
      communist country like Hungary.

PMID- 11511057
TI  - Reviewing psychosocial interventions for family carers of people with dementia.

PMID- 11511058
TI  - A systematic review of the effectiveness of psychosocial interventions for carers
      of people with dementia.
AB  - Historically, there have been many attempts to develop interventions to support
      the carers of people with dementia. To date the evidence of effectiveness has
      been limited. However, the success of psychosocial interventions for carers of
      people with schizophrenia has suggested the possibility of utilizing this
      approach. A systematic review was undertaken to assess the evidence of
      effectiveness for psychosocial interventions with carers of people with dementia.
      Thirty controlled trials that evaluated a psychosocial approach were identified.
      The overall methodological quality of these studies was poor, particularly with
      regard to sample size, and methods of random allocation. Individualized
      interventions that utilized problem solving and behaviour management demonstrated
      the best evidence of effectiveness. This approach is also closest to the
      effective model of psychosocial interventions currently in use with other severe
      and enduring illnesses. This suggests that there is scope for developing
      interventions, based more specifically on this model, for supporting the carers
      of people with dementia.

PMID- 11511059
TI  - Psychosocial interventions for caregivers of people with dementia: a systematic
      review.
AB  - The content of interventions for caregivers of dementia patients is highly
      varied. None of the reviews conducted to date have focused on evaluating the
      effects of the content of interventions exclusively for dementia caregivers, and
      this issue is not well understood. The purpose of this review was to first
      identify the type of components (e.g. education, counselling) that have been
      utilized in psychosocial/psycho-educational interventions for dementia
      caregivers, and to evaluate the success of the different components or
      combination of components in producing positive outcomes for dementia caregivers.
      Forty studies were included in the review. Approximately two-thirds of the
      interventions did not show improvements in any outcome measures. Among those
      studies, which did demonstrate improvements, the inclusion of social components
      (e.g. social support) or a combination of social and cognitive (e.g. problem
      solving) components seemed to be relatively effective. It is important to note,
      however, that these analyses were based on small numbers and the review was
      limited by a number of methodological issues (e.g. poor description of
      interventions). To advance our understanding of the efficacy of psychosocial
      interventions for caregivers of people with dementia, a more systematic approach
      is required. Intervention components need to be carefully contrasted in
      appropriately designed studies of sufficient size.

PMID- 11511060
TI  - Comparison of older adult subject and proxy responses on the SF-36 health-related
      quality of life instrument.
AB  - Studies of older adults' health status and health-related quality of life (HRQoL)
      often rely on proxy responses when subjects have problems that affect their
      ability to respond. With the increased interest in outcomes research in health
      care, it is important to examine proxy reliability on HRQoL instruments. This
      study compares 32 pairs of subject-andproxy responses on the eight subscales and
      two summary scales of the Short Form 36 (SF-36). Subjects and their proxies,
      recruited from senior centers and residential facilities, were interviewed face
      to-face within a seven-day period. Subjects were 60 years of age or older and had
      passed a brief cognitive screen, and proxies were geographically proximate and
      had seen the subject during the past week. Results showed that although moderate
      intra-class correlations were found on six of the eight measures, an item-level
      kappa statistic indicated poor to fair agreement on all subscales except items of
      Physical Functioning and Role Physical. Moreover, paired t-tests revealed proxy
      mean scores that were significantly lower on the Physical Functioning, Vitality,
      and Mental Health subscales. Given the mixed findings, until further research is
      done, researchers and clinicians should exercise caution when using proxy
      responses for older adults with the SF-36.

PMID- 11511061
TI  - Evaluating geriatric medical outpatients with the Beck Depression Inventory
      Fastscreen for medical patients.
AB  - To ascertain how effective the seven-item Beck Depression Inventory-FastScreen
      for medical patients (BDI-FS) was in screening geriatric (> 55 years old)
      patients for depression, the BDI-FS and the 15-item Geriatric Depression Scale
      (GDS-S) were administered to 33 (44%) male and 42 (56%) female outpatients who
      were scheduled for routine office visits by physicians specializing in geriatric
      medicine. The internal consistency of the BDI-FS was high (coefficient alpha =
      0.83), and it was positively correlated with the GDS-S, r = 0.81, p < 0.001. The
      BDI-FS scores were not related to sex, age, ethnicity, or type of medical
      diagnosis, but were positively correlated with a diagnosis of depression (r =
      0.49, p < 0.001) and being prescribed an antidepressant (r = 0.55, p < 0.001). A
      BDI-FS cut-off score of four and above had 100% sensitivity and 84% specificity
      rates, respectively, for identifying patients who were and were not diagnosed
      with depression.

PMID- 11511062
TI  - Aspects of mental health among older lesbian, gay, and bisexual adults.
AB  - This study examined aspects of mental health among 416 lesbian, gay, and bisexual
      adults aged 60 to 91 years old, attending social and recreational programs.
      Mental health indicators were perceived mental health status; self-esteem;
      internalized homophobia; loneliness; alcohol and drug abuse; and suicidality.
      Better mental health was correlated with higher self-esteem, less loneliness, and
      lower internalized homophobia. Compared to women, men reported significantly more
      internalized homophobia, alcohol abuse, and suicidality related to their sexual
      orientation. Less lifetime suicidal ideation was associated with lower
      internalized homophobia, less loneliness, and more people knowing about
      participants' sexual orientation.

PMID- 11511064
TI  - Explanation for low prevalence of PTSD among older Finnish war veterans: social
      solidarity and continued significance given to wartime sufferings.
AB  - A relatively low rate of Post-Traumatic Stress Disorder (PTSD) (<10%), has been
      reported among Finnish veterans of World War II. Possible explanations for this
      are explored by means of depth interviews with 30 veterans (mean age of 77
      years), staying at a Disabled Veterans Hospital and at a Rehabilitation Centre,
      drawing on an Attachment Theory perspective. The Impact of Event Scale, the
      General Health Questionnaire, as well as health survey, medical problems, and war
      experience questions, were administered as part of the interview. A low rate of
      PTSD symptomatology was also reported in this sample alongside a relatively high
      level of subjective well-being. Without exception, they spoke freely about the
      war, often with emotion. Themes that received emphasis in their accounts included
      the Finnish fighting spirit and the strong reciprocal bonds of loyalty that were
      felt during the war. The war now featured prominently as part of their integrity
      as old men, representing a honourable task that they had been called on to
      fulfil. The significance they attributed to the war had not waned with time.
      Although this study of older war veterans, in common with other such studies,
      does not consider the less resilient who have not survived to old age, it does
      suggest that the strong community spirit built up in the war and continued in
      Finnish veterans' association after the war together with the continuing esteem
      of Finnish society, has contributed to the high levels of well-being expressed by
      the survivors.

PMID- 11511063
TI  - Personality profiles among normal aged individuals as measured by the NEO-PI-R.
AB  - The revised Neuroticism (N), Extraversion (E), Openness (O) to experience
      Personality Inventory (NEO-PI-R) is a multidimensional measure of normal
      personality traits that is intended to assess five major personality dimensions
      or domains-N, E, O, Agreeableness (A), and Conscientiousness (C). Although
      several studies have been conducted examining N, E, and O factors in people 65
      through to 85 years old, there has been little research examining all five-core
      domains of personality in individuals 85 and older. We compared the NEO-PI-R
      domains and facet traits in the middle-aged/young-old versus old-old normal
      subjects. Thirty-eight community-dwelling subjects (22 women, 16 men) free from
      major neuropsychiatric disorders were given the NEO-PI-R, a self-administered 240
      item personality inventory, assessing 30 facet traits within the five domains. We
      compared the scores of 21 middle-aged and young-old (age 50-84) individuals, to
      those of 17 old-old (age 85-100) subjects. The personality profiles of the two
      groups were similar except that the old-old group had lower scores on
      Extraversion, and four of the 30 facet traits (warmth, positive emotions,
      impulsiveness, and order) compared to the middle-aged/young-old group. These
      results were limited by the cross-sectional design and small sample size.
      Nonetheless, the findings suggest that the middle-aged/young-old and the old-old
      normal subjects have fairly similar personality traits.

PMID- 11511065
TI  - World war II veterans, social support, and veterans' associations.
AB  - People use many different coping strategies to deal with their traumatic
      recollections. Twenty-five British World War II veterans were interviewed
      regarding the ways they used social support both during the war and in the years
      afterwards. The findings demonstrate that social support is used in fundamentally
      different ways. During the war comradeship was particularly important and even
      fifty years after the war comrades are still a valuable resource for discussing
      war experiences, and dealing with the emotional content of traumatic
      recollections. Veterans rely on wives and families to help deal with the more
      physical and practical elements of coping, but tend not to discuss their
      traumatic memories with them. The findings show that social support is an
      important lifelong coping strategy for World War II veterans.

PMID- 11511066
TI  - The long-term consequences of war: the experience of World War II.
AB  - Seven hundred and thirty-one World War II and Korean War veterans completed a
      questionnaire about their experiences and their current psychological reactions
      to the war. Nineteen percent scored above the cut-off points for both the General
      Health Questionnaire and the (war-related) Impact of Event Scale, demonstrating
      that, even over 50 years after the event, many veterans still experience problems
      relating to their war experiences. Psychological distress was in part directly
      related to particular experiences, but intrusion and avoidance both played an
      important role as mediating variables. Other factors, such as prisoner of war
      (POW) status, type of service, rank, and illness were also considered. The
      findings indicate that the effects of a traumatic experience such as war can
      persist into later life.

PMID- 11511067
TI  - The relationship between severity of dementia and subjective well-being.
AB  - The purpose of this study was to describe the relationship between cognitive
      deficits and self-reported subjective well-being (depression, life satisfaction,
      and perceived social support). Sixty-three participants who suffered from mild to
      moderate dementia were interviewed with standardized measurements of subjective
      well-being. Reliability and validity of the instruments were satisfactory. Zero
      order correlations showed significant correlations between depression, life
      satisfaction, and perceived social support. Cognitive functioning correlated
      negatively with perceived social support. Hierarchical regression analyses
      revealed that the interaction of physical diseases and cognitive functioning
      produced a significant change in depressive symptoms and life satisfaction.
      Participants with mild dementia reported more depressive symptoms and less life
      satisfaction than persons with more severe dementia, if there were few
      constraints on physical health.

PMID- 11511068
TI  - Cognitive behavioural psychotherapy: a comparison between younger and older
      adults in two inner city mental health teams.
AB  - There is little evidence about the efficacy of Cognitive Behavioural Therapy
      (CBT) in the older adult population. Research highlights that the preferred
      treatment for this group appears to be medication. This study compares an older
      adult mental health service with a younger adult service in terms of range of
      referrals, outcomes, attendance rates and length of time in therapy. The range of
      disorders referred was a wide mix of anxiety disorders and depression. There were
      no significant differences in therapy outcomes apart from home adjustment
      measures where older adults showed greater improvement. Younger adults showed
      significantly higher rates of non- attendance (DNA) and had higher dropout rates.
      Possible reasons for this are discussed. CBT appeared effective in both age
      groups, however older adults were treated more quickly due to a higher attendance
      rate.

PMID- 11511069
TI  - The long-term psychological effects of traumatic wartime experiences on older
      adults.

PMID- 11511070
TI  - Proceedings of the Conference on Action and Visuo-Spatial Attention:
      Neurobiological Bases and Disorders. Konigswinter, Germany, November 2000.

PMID- 11511071
TI  - Hepatopulmonary syndrome in transplant centres at different altitudes.

PMID- 11511072
TI  - Comeback of Anopheles funestus in Sahelian Senegal.

PMID- 11511073
TI  - Medical education.

PMID- 11511074
TI  - Chagas' disease.

PMID- 11511075
TI  - Is ancient Greek a dead language?

PMID- 11511076
TI  - Magnetic resonance imaging of the breast for preoperative evaluation in patients
      with localized breast cancer.

PMID- 11511077
TI  - Heat shock proteins: endogenous modulators of apoptotic cell death.
AB  - The highly conserved heat shock proteins (HSPs) accumulate in cells exposed to
      heat and a variety of other stressful stimuli. HSPs, which function mainly as
      molecular chaperones, allow cells to adapt to gradual changes in their
      environment and to survive in otherwise lethal conditions. The events of cell
      stress and cell death are linked and HSPs induced in response to stress appear to
      function at key regulatory points in the control of apoptosis. HSPs include
      antiapoptotic and proapoptotic proteins that interact with a variety of cellular
      proteins. Their expression level can determine the fate of the cell in response
      to a death stimulus, and apoptosis-inhibitory HSPs, in particular HSP27 and
      HSP70, may participate in carcinogenesis. This review summarizes apoptosis
      regulatory function of HSPs.

PMID- 11511078
TI  - Low-intensity pulsed ultrasound stimulates a bone-forming response in UMR-106
      cells.
AB  - Low-intensity (<100 mW/cm(2)) pulsed ultrasound (US) is an established therapy
      for fracture repair. In both animal and human trials, such US has been shown to
      facilitate fresh fracture repair and initiate healing in fractures with repair
      defects. However, the mechanism by which US achieves these outcomes is not clear.
      One possible mechanism is the direct stimulation of bone formation. To
      investigate this hypothesis, the current study investigated the mRNA response of
      isolated bone-forming cells (UMR-106 cells) to a single 20-min dose of low
      intensity pulsed US. Using a novel US-cell coupling method, US was found to
      stimulate expression of the immediate-early response genes c-fos and COX-2 and
      elevate mRNA levels for the bone matrix proteins ALP and OC. These findings
      suggest that low-intensity pulsed US has a direct effect on bone formation. This
      may contribute to the beneficial effect of low-intensity pulsed US on fracture
      repair.

PMID- 11511079
TI  - Systematic search for single nucleotide polymorphisms in the insulin gene:
      evidence for a high frequency of -23T-->A in Japanese subjects.
AB  - It has recently been shown that the A/A genotype at g.-23 of the insulin gene
      correlates with impaired insulin secretion in response to body weight gain in
      subjects of European descent. To examine whether there are single nucleotide
      polymorphisms (SNPs) in the insulin gene associated with type 2 diabetes, all
      exons with their flanking sequences for 113 Japanese type 2 diabetic patients and
      99 nondiabetic control subjects were analyzed using PCR direct sequencing. We
      have only found g.-23T --> A, 806G --> C, 1128T --> C, and 1141A --> C, which
      have previously been reported in alpha (A-C-C-C) and beta (T-G-T-A) alleles. The
      allele frequency of -23T --> A in control Japanese subjects was 97.4%, whereas
      that in Europeans is about 30%. The A/A genotype was found in 94 of 99 Japanese
      subjects (94.9%) and the allele frequencies of 806G --> C, 1128T --> C, and 1141A
      --> C were all 96.5%. The estimated haplotype frequencies were (A-C-C-C) (96.0%),
      (T-G-T-A) (2.0%), (A-G-T-A) (1.5%), and (T-C-C-C) (0.5%). No association of these
      SNPs or haplotypes with type 2 diabetes was evident. Thus, the A/A genotype at
      the g.-23 of insulin gene was generally high in Japanese subjects, which could
      account for the fact that they typically secrete lower levels of insulin.

PMID- 11511080
TI  - Production of transgenic quails with high frequency of germ-line transmission
      using VSV-G pseudotyped retroviral vector.
AB  - We report here the production of transgenic quails using a replication-defective
      pantropic retroviral vector based on Moloney murine leukemia virus (MoMLV)
      pseudotyped with vesicular stomatitis virus G protein (VSV-G). The retroviral
      vector was injected into laid quail embryos at the blastodermal stage, and the
      embryos were incubated to hatch to produce G(0) transgenic quails. Among 134
      embryos subjected to viral injection, 37 hatched. The viral vector sequence was
      detected in the tissues of all G(0) quails. The germ-line transmission efficiency
      of G(0) quails mated with nontransgenic quails was more than 80% on average.
      Southern blot analysis revealed that the G(1) transgenic progeny had one to three
      copies of the transgene. The expression of vector-encoded neomycin-resistance
      gene under the control of the Rous sarcoma virus (RSV) promoter was observed in
      several tissues including heart and muscle of both G(1) and G(2) transgenic
      offspring. Due to the high frequency of germ-line transmission, this method may
      markedly facilitate the production of transgenic avian.

PMID- 11511081
TI  - Aerosolization of cationic lipid-DNA complexes: lipoplex characterization and
      optimization of aerosol delivery conditions.
AB  - This study deals with the development of gene therapy in the treatment of lung
      diseases. It reports on the use of ultrasonic nebulization to administer plasmid
      lipid complexes to the lungs of mice to transfect their epithelial cells. A
      plasmid complexed to cationic lipids was aerosolized using an ultrasonic
      nebulizer. We then characterized the lipoplex size and visualized the lipoplex by
      electron microscopy. Finally, we assessed the in vivo transgene expression in the
      lungs further to the aerosolization of different lipid-plasmid formulations. The
      nebulizer-generated particles were small and looked like a string composed of
      little and more or less cubic units. Transgene expression was detected in the
      lungs of mice further to a 20-min exposure to aerosol particles produced with the
      ultrasonic nebulizer. The results obtained with our optimized plasmid-lipid-NaCl
      formulation suggest that this route can be used to administer an appropriate gene
      to the airways for the treatment of respiratory disorders.

PMID- 11511082
TI  - Anchorage-independent growth of fibroblasts that express a truncated IGF-I
      receptor.
AB  - The purpose of this investigation was to study signaling by an insulin-like
      growth factor I receptor (IGF-I R) that lacks the extracellular portion of the
      receptor. We transfected IGF-I R-negative mouse embryo fibroblasts with a
      truncated IGF-I R consisting of only the transmembrane and cytoplasmic part of
      the beta subunit. Proliferation as assessed by counting cells was the same for
      vector only transfectants and the truncated receptor transfectants in defined
      medium containing EGF and PDGF. In contrast, anchorage-independent growth as
      measured by colony formation in soft agar was markedly increased for the
      truncated IGF-I R transfectants compared to the vector transfectants. MAP-kinase
      activity in the truncated IGF-I R transfectants was not higher than in the vector
      transfectants; however, PI 3-kinase activity was significantly higher in the IGF
      I R transfectants. These results provide evidence that an IGF-I receptor
      consisting of only the transmembrane and cytoplasmic domain of the beta subunit
      can signal pathways leading to anchorage-independent growth.

PMID- 11511083
TI  - Dystrophin in adult zebrafish muscle.
AB  - Mutations in the human dystrophin gene are implicated in the fatal muscle wasting
      disease Duchenne Muscular Dystrophy (DMD). This gene expresses a sarcolemmal
      associated protein that is evolutionarily conserved, underpinning its important
      role in the architecture of muscle. In terms of DMD modelling, the mouse has
      served as a suitable vertebrate species but the pathophysiology of the disease in
      the mouse does not entirely mimic human DMD. We have examined the zebrafish in
      order to expand the repertoire of vertebrate species for muscle disease
      modelling, and to dissect further the functional interactions of dystrophin. We
      report here the identification of an apparent zebrafish orthologue of the human
      dystrophin gene that expresses a 400-kDa protein that is localised to the muscle
      membrane surface. These data suggest that the zebrafish may prove to be a
      beneficial vertebrate model to examine the role and functional interactions of
      dystrophin in disease and development.

PMID- 11511084
TI  - Hyperphosphorylation and association with RBP of the intracellular domain of
      Notch1.
AB  - Although the intracellular domain of Notch1 is phosphorylated and it associates
      with members of the CSL family, the relationship of these events is poorly
      understood. Using in vivo [(32)P]orthophosphate labeling of cells expressing
      transfected Notch1, we observed that the furin cleaved Notch1 (TMIC) and the
      soluble intracellular forms (NICD), but not the full-length molecule were
      phosphorylated. Furthermore, transfected NICD molecules showed a significantly
      greater specific activity of phosphorylation, or hyperphosphorylation, compared
      to TMIC molecules. Hyperphosphorylation of NICD was also observed when NICD was
      generated by an endogenous intramembraneous cleavage of TMIC. However, TMIC
      molecules bearing a mutation that reduces intramembraneous cleavage (V1744K) did
      not show an enhanced incorporation of phosphate, suggesting that cleavage is
      required for hyperphosphorylation. Using deletion constructs to map the sites of
      phosphorylation, we observed that a domain of 93 amino acids downstream of the
      ankyrin repeats incorporated the majority of (32)P in vivo. This sequence was
      also required for activation of the HES-1 promoter. In addition, we observed that
      hyperphosphorylated forms of the intracellular domain were more likely to
      interact with the transcriptional coactivator RBP. However, dephosphorylation
      experiments showed that the interaction between RBP and the intracellular domain
      of Notch was not dependent upon Notch1IC phosphorylation. These studies reveal
      that phosphorylation of the intracellular domain of the Notch receptor is a
      dynamic process during the events of Notch signal transduction.

PMID- 11511085
TI  - Cofilin activation during Ca(2+)-triggered secretion from adrenal chromaffin
      cells.
AB  - Cofilin is one of the major actin depolymerizing proteins in eukaryotic cells and
      involved in many membrane modulating activities, such as cell growth and
      motility. Here we examined whether cofilin is activated upon Ca(2+) regulated
      noradrenalin secretion from bovine adrenal chromaffin cells. We found that
      triggering exocytosis by nicotine causes a dephosphorylation and thereby
      activation of cofilin. Furthermore, in permeabilized chromaffin cells the
      addition of Ca(2+) alone is sufficient to trigger both, regulated exocytosis and
      cofilin activation. This is consistent with cofilin activation being required for
      actin reorganization during exocytosis.

PMID- 11511086
TI  - The antipsychotic drugs sertindole and pimozide block erg3, a human brain K(+)
      channel.
AB  - The antipsychotic drugs sertindole and pimozide are known to prolong the QT
      interval on the electrocardiogram via a high affinity block of the cardiac K(+)
      channel known as HERG (human ether-a-go-go-related gene; erg1). We wished to test
      whether these drugs also displayed high affinity for the related neuronal K(+)
      channel erg3. The cDNA encoding erg3 channel was cloned from a human brain
      library. Northern analysis confirmed that the channel was localized to brain
      relative to other tissues including heart, liver and lung. Within the brain, erg3
      was expressed in higher amounts in the frontal lobe and cerebellum relative to
      the temporal, parietal and occipital lobes. Transient expression of erg3 in
      Chinese hamster ovary cells produced outwardly directed K(+) currents that
      activated at approximately -50 mV and produced a large transient component at
      positive membrane potentials. Inward tail currents measured at -100 mV were
      blocked in a dose-dependent fashion by sertindole resulting in an IC(50) value of
      43 nM. Significant inhibition was observed at concentrations as low as 3 nM.
      Block of erg3 by sertindole also displayed a positive voltage-dependence.
      Pimozide blocked erg3 channel currents with an IC(50) of 103 nM and significant
      inhibition was noted at concentrations of 10 nM and higher. We conclude that erg3
      can be blocked by certain antipsychotic drugs like sertindole and pimozide.
      Inhibition of erg3 or related K(+) channels in the brain may contribute to the
      efficacy/side effect profiles of some antipsychotic drugs.

PMID- 11511087
TI  - Vascular endothelial growth factor: acting as an autocrine growth factor for
      human gastric adenocarcinoma cell MGC803.
AB  - Vascular endothelial growth factor (VEGF) is known to be a highly specific
      mitogen for endothelial cells through two high-affinity tyrosine kinase
      receptors, VEGFR-1 and VEGFR-2, which are almost specifically expressed in
      endothelial cells. However, recent findings showed that VEGF receptors may also
      expressed by nonendothelial cells, especially by tumor cells. To further
      understand the functional expression of VEGF receptors by nonendothelial cells,
      our preliminary screening detected the expression of VEGFR-2 in 115 different
      paraffin-embedded cancer specimens including 35 cases of bladder tumor, 30 cases
      of breast cancer, 25 cases of intestinal cancer, and 25 cases of lung cancer with
      immunohistochemistry. The results showed that VEGFR-2 was widely expressed in
      different tumor tissues. By reverse transcription PCR, NCI-H23, NCI-H460, MGC803,
      MDA-MB-231, 293, and MCF7 cells were evaluated for the mRNA expression of both
      VEGF and VEGFR-2. The data indicated that all these tumor cell lines expressed
      detectable amounts of VEGF mRNA, but only 293, MCF7, and MGC803 cells coexpressed
      VEGFR-2. Immunoblot analysis also demonstrated the expression of VEGFR-2 at
      protein level. We further demonstrate that exogenous rhVEGF(165) could stimulate
      cell growth in MGC803, a tumor cell line derived from gastric adenocarcinoma, in
      a dose- and time-dependent manner. Furthermore, the antibodies against
      rhVEGF(165) and VEGFR-2 could block rhVEGF(165)-mediated proliferation of MGC803
      cells. These unexpected results provided direct evidence that VEGF may act as an
      autocrine growth factor to induce the proliferation of gastric adenocarcinoma
      cells as well as tumor angiogenic cells, thus suggesting a promising tumor
      therapeutic application based upon the VEGF system.

PMID- 11511088
TI  - Identification of amino-terminal pro-C-type natriuretic peptide in human plasma.
AB  - We report the first identification of a circulating peptide from the amino
      terminal end of proCNP. A specific radioimmunoassay was established based on
      antisera to the synthetic peptide proCNP(1-15). Extracts of plasma, drawn from
      patients with congestive heart failure or from sheep with experimental heart
      failure, were subjected to size exclusion and reverse-phase high-pressure liquid
      chromatography (HPLC) coupled to radioimmunoassay (RIA). These studies revealed
      the presence of an immunoreactive peptide with a molecular weight (M(r)
      approximately 5 kDa) similar to that expected for NT-proCNP(1-50), a potential
      fragment released during processing of pro(CNP). The same material was isolated
      from extracts of homogenized ovine pituitary, a tissue known to be a relatively
      enriched source of CNP. Plasma NT-proCNP levels in 22 patients with congestive
      heart failure (9.7 +/- 0.5 pmol/L, mean +/- SEM, range 5.4-13.7 pmol/L) were
      raised (P = 0.003) compared to those in 16 healthy volunteers (7.4 +/- 0.3
      pmol/L, range 5.7-10.7 pmol/L) and were higher than levels reported for CNP in
      similar subjects. This first identification of circulating NT-proCNP opens the
      possibility of studying the factors regulating CNP production and metabolism in
      vivo.

PMID- 11511089
TI  - Opposite regulation of hypothalamic orexin and neuropeptide Y receptors and
      peptide expressions in obese Zucker rats.
AB  - Many hyothalamic neuropeptides are involved in the regulation of food intake and
      body weight. The orexins (OX) which are synthesized in the lateral hypothalamus
      are among the most recently characterized whereas neuropeptide Y (NPY) belongs to
      a group of "older" peptides extensively studied for their effects on feeding
      behavior. Both stimulate food ingestion in rodents. In this experiment, we
      measured the expressions of these peptides as well as of their receptors (OX1-R
      and OX2-R, Y1 and Y5) in the hypothalamus of obese hyperphagic and lean Zucker
      rats by real-time RT-PCR using the TaqMan apparatus. NPY mRNA expression in the
      obese rats was significantly increased by a factor of 10 (P < 0.002) whereas
      expressions of the Y1 and Y5 receptors were decreased by 25% (P < 0.01) and 50%
      (P < 0.002), respectively. Their prepro-orexin mRNA expression was more than
      twofold decreased (P < 0.01) and expressions of their OX receptors 1 and 2 mRNA
      were five- and fourfold increased (P < 0.05), respectively. An inverse phenomenon
      was therefore noted between the two peptides: for NPY, increased levels and
      downregulation of receptors; and for OX, diminished levels with upregulation of
      receptors. The reasons for these changes might be linked to the absence of leptin
      signaling as similar profiles are found in the ob/ob mice. For orexins at least,
      other factors such as hyperglycemia might be involved. Based on anatomical
      considerations, a direct effect of NPY or of other brain peptides such as CRH
      cannot be excluded. We conclude that the diminution in the OX tone might
      participate in a counterregulatory system necessary to limit the noxious effects
      of NPY on food intake and body weight.

PMID- 11511090
TI  - Evaluation of glycated insulin in diabetic animals using immunocytochemistry and
      radioimmunoassay.
AB  - Glycated insulin was evaluated in plasma and biological tissues of diabetic
      animal models by immunocytochemistry (ICC) and a novel radioimmunoassay. Glycated
      insulin circulated at 0.10 +/- 0.04 ng/ml and 2.20 +/- 0.14 ng/ml in lean and
      diabetic obese (ob/ob) mice, corresponding to 12.5 and 9.8% total plasma insulin,
      respectively. The concentration of glycated insulin was elevated 22-fold in obese
      mice compared to controls (P < 0.001). In the pancreas, glycated insulin was 48
      +/- 10 and 83 +/- 4 ng/g wt (P < 0.05) in lean and obese mice, respectively,
      representing approximately 2% total insulin in the diabetic pancreas (4.60 +/-
      0.17 microg/g wt). ICC revealed fluorescent positively stained cells in
      pancreatic islets from hydrocortisone (HC)-treated diabetic rats. Fasting of HC
      treated rats, resulted in 3-fold and 15-fold reductions in plasma glycated
      insulin (P < 0.01) and insulin (P < 0.001), respectively. Following a 30 min
      feeding period in these insulin resistant rats, plasma glucose, insulin, and
      glycated insulin increased (P < 0.001) rapidly with 1.4-, 1.6-, and 2.9-fold
      elevations, respectively. Injection of HC-treated rats with insulin (50 U/kg)
      resulted in a rapid 33% decrease of plasma glucose (P < 0.001) and a marked 4
      fold increase in plasma insulin (P < 0.01), whereas glycated insulin
      concentrations remained unchanged. Since glycation of insulin impairs biological
      activity, physiologically regulated secretion of glycated insulin into the
      circulation in diabetic animal models suggests a role in the pathogenesis of
      diabetes.

PMID- 11511091
TI  - Nitric oxide inhibits selectively the 17beta-estradiol-induced gene expression
      without affecting nongenomic events in HeLa cells.
AB  - 17beta-Estradiol (E2) induces genomic (i.e., pC3-luciferase promoter-reporter
      construct expression) and nongenomic (i.e., DNA synthesis and IP(3) production)
      effects in HeLa cells only after transient transfection with the human estrogen
      receptor alpha (ERalpha) reporter plasmid. Here the effect of nitric oxide (NO)
      on both E2-induced effects in transiently transfected HeLa cells is reported.
      Remarkably, the E2-dependent gene transcription is inhibited dose-dependently by
      NO. By contrast, DNA synthesis and IP(3) production, representing nongenomic E2
      dependent effects, are unaffected by NO. The selective NO action on E2-induced
      functions may be related to NO-mediated chemical modification(s) of the Cys
      residues present in the DNA recognition domain of ERalpha impairing DNA binding.

PMID- 11511092
TI  - Mouse coq7/clk-1 orthologue rescued slowed rhythmic behavior and extended life
      span of clk-1 longevity mutant in Caenorhabditis elegans.
AB  - The coq7/clk-1 gene was isolated from the long-lived mutant of Caenorhabditis
      elegans and was suggested to play a regulatory role in biological rhythm and
      longevity. The mouse COQ7 is homologous to Saccharomyces cerevisiae COQ7/CAT5
      that is required for the biosynthesis of coenzyme Q (ubiquinone), an essential
      messenger in mitochondrial respiration. In the present study, we characterized
      the expression and processing of mouse COQ7. We found that COQ7 is highly
      expressed in tissues with high energy demand such as heart, muscle, liver, and
      kidney in mice. Biochemical analysis revealed that COQ7 is targeted to
      mitochondria where it is processed to mature form. Transgenic expression of mouse
      coq7 completely rescued the slowed rhythmic behaviors of clk-1 such as
      defecation. In life-span analysis, transgenic expression reverted the extended
      life span of clk-1 to the comparable level with wild-type control. These data
      strongly suggested that coq7 plays a pivotal role in the regulation of biological
      rhythms and the determination of life span in mammalian species.

PMID- 11511093
TI  - PPARgamma ligands inhibit TNF-alpha-induced LOX-1 expression in cultured
      endothelial cells.
AB  - Endothelial dysfunction or activation, elicited by oxidized low-density
      lipoprotein (OxLDL), has been implicated in the initiation and progression of
      atherosclerosis. We elucidated whether tumor necrosis factor-alpha (TNF-alpha)
      induced endothelial OxLDL receptor, lectin-like OxLDL receptor-1 (LOX-1), mRNA
      expression is modified by peroxisome proliferator-activated receptor (PPAR)
      activators in cultured bovine aortic endothelial cells (BAEC). We confirmed that
      both PPARalpha and PPARgamma were expressed in BAEC by reverse transcription
      polymerase chain reaction analysis. Natural PPARgamma ligand 15-deoxy
      Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) and the thiazolidinediones,
      pioglitazone and troglitazone, decreased TNF-alpha-induced LOX-1 mRNA expression
      in BAEC. LOX-1 expression induced by phorbol 12-myristrate 13-acetate was also
      inhibited by 15d-PGJ(2). In contrast, PPARalpha ligands, Wy14643 and fenofibric
      acid, did not alter TNF-alpha-induced LOX-1 expression. TNF-alpha-induced
      immunohistochemical staining of LOX-1 was suppressed by 15d-PGJ(2) but not
      Wy14643. Taken together, PPARgamma activators inhibit TNF-alpha-induced LOX-1
      expression in cultured BAEC, which may beneficially influence inflammatory
      responses in atherosclerosis.

PMID- 11511094
TI  - Characterization of tissue- and cell-type-specific expression of a novel human
      septin family gene, Bradeion.
AB  - Expression changes in subsets of genes occur in the course of altering cell
      fates, i.e., aging, cell death, and carcinogenesis. These changes simultaneously
      provide the good candidate as a biomarker for monitoring cancer. We have
      identified a novel human septin family gene, Bradeion, from adult brain cDNA
      library by a monoclonal antibody CE5. Northern blot and in situ hybridization
      analysis showed that Bradeion has two distinct transcripts, approximately 2.2 and
      1.7 kb length (alpha and beta, respectively) mainly in brain and slightly in
      heart, and no expression in any fetal organs. Haplotype analysis placed the gene
      location at 17q23. The gene contains GTPase motifs highly conserved in the septin
      family genes that are essential for cytokinesis and cell separation. The
      transcript of beta form lacks a hydrophobic region, which suggests that this form
      arises from a single Bradeion gene through unique RNA splicing. Interestingly,
      this brain-specific Bradeion gene is also expressed in two human cancers,
      colorectal cancer and malignant melanoma. Ectopic expression of normal Bradeion
      alpha and beta transcripts were confirmed both in patients' tumor samples and in
      in vitro cultured human cancer cell lines. Thus the Bradeion provides valuable
      tools as a tumor-specific and selective marker.

PMID- 11511095
TI  - Disulfide bridge conformers of mature BMP are inhibitors for heterotopic
      ossification.
AB  - Heterotopic ossification is a frequent complication in patients who have suffered
      head and neck traumas or undergone total hip replacement. Heterotopic
      ossification occurs when osteogenic precursor cells present at the ectopic site
      receive the necessary signal(s) to differentiate into osteoblasts. At the protein
      level, the key factors in differentiation of cells to the osteogenic lineage are
      BMPs. Stable BMP variants derived from the identical amino acid sequence but with
      different disulfide bridge configurations have been investigated and found to be
      capable of inhibiting ossification in vitro and in vivo in rodents. These
      findings provide a concept for the straightforward development of a novel class
      of BMP antagonists that could lead to new treatments for traumatically and
      genetically induced heterotopic ossification and also, possibly, for disorders in
      which other members of the TGF-beta superfamily are involved.

PMID- 11511096
TI  - SNO is a probable target for gene amplification at 3q26 in squamous-cell
      carcinomas of the esophagus.
AB  - Amplification of the 3q26 region appears to occur frequently among esophageal
      squamous cell carcinomas (ESCs). We examined ESC cell lines for amplification and
      expression levels of four genes in this region: SNO and EVI1, which encode
      proteins antagonizing transforming growth factor-beta signaling, and two other
      putative target genes, TERC and PIK3CA. Amplification of SNO was accompanied by
      significant increases in its expression level, suggesting that this gene is
      activated in an amplification-dependent manner. SNO was also amplified in 5 of 44
      primary ESCs (11.4%). However, expression levels of EVI1, TERC, and PIK3CA did
      not correlate with their copy-numbers, even though EVI1 and TERC showed the same
      amplification pattern as SNO. Taken together, the data suggest that of the four
      candidates, SNO is the most probable target in the 3q26 amplicon for involvement
      in the progression of ESC.

PMID- 11511097
TI  - Cell-type-specific expression of a TESK1 promoter-linked lacZ gene in transgenic
      mice.
AB  - Testicular protein kinase 1 (TESK1) is a serine/threonine kinase highly expressed
      in testicular germ cells and has the potential to phosphorylate cofilin and
      induce actin cytoskeletal reorganization. We examined the expression of a lacZ
      reporter gene linked to a 9.0-kb 5'-flanking region of TESK1 gene in transgenic
      mice. A high level of lacZ expression was observed in testicular germ cells only
      at stages after pachytene spermatocytes, the expression patterns being similar to
      those of TESK1 mRNA in rat testis, determined by in situ hybridization.
      Expression of lacZ was also detected in renal proximal tubules, cardiac myocytes,
      and specific neurons in the central nervous system in adult transgenic mice.
      Whole-mount staining revealed the expression of lacZ in neural tissues in
      embryonic mice. These results suggest the cell-type- and stage-specific
      expression of TESK1 gene and the diverse and specific physiological functions of
      TESK1, including those in spermatogenesis and neural development.

PMID- 11511098
TI  - GOA, a novel gene encoding a ring finger B-box coiled-coil protein, is
      overexpressed in astrocytoma.
AB  - Serial analysis of gene expression (SAGE) was used to identify a gene named GOA
      (gene overexpressed in astrocytoma), which codes for a novel Ring finger B-box
      coiled-coil (RBCC) protein. Northern blot hybridization showed overexpression of
      GOA in 9 of 10 astrocytomas. Except for kidney, in which high expression was
      found, expression levels in normal tissues were low and comparable to normal
      brain. Immunohistochemistry demonstrated presence of GOA, with prominent nuclear
      staining, in astrocytoma tumor cells and astrocytes of fetal brain, but virtual
      absence in mature astrocytes. Overexpression was not due to amplification, since
      amplification of GOA was only found in one of 65 astrocytomas. GOA was localized
      to 17q24-25, a region that is frequently gained or amplified in a number of other
      tumor types. GOA contains two LXXLL motifs, which are thought to be important for
      nuclear receptor binding. Our data suggest an important role of GOA in the
      process of dedifferentiation that is associated with astrocytoma tumorigenesis
      and possibly with that of other tumor types as well.

PMID- 11511099
TI  - Targeted deletion of the cytosolic domain of tissue factor in mice does not
      affect development.
AB  - The role of the cytosolic domain of tissue factor (TF) in signal transduction and
      gene regulation was studied in mice with a targeted deletion of the 18 carboxy
      terminal intracellular amino acids. This deletion was introduced in exon 6 along
      with a floxed neo(R) selection cassette in intron 5 using homologous
      recombination in embryonic stem cells. Removal of the floxed neo(R) cassette by
      in vivo Cre-mediated loxP recombination yielded TF(+/deltaCT) and
      TF(deltaCT/deltaCT) mice. In contrast to TF(-/-) mice, TF(+/deltaCT) and
      TF(deltaCT/deltaCT) mice displayed normal embryonic development, survival,
      fertility, and blood coagulation. Factor VIIa or factor Xa stimulation produced
      similar p44/42 MAPK activation in TF(+/+) and TF(deltaCT/deltaCT) fibroblasts.
      These data, based on expression of a TF(deltaCT) molecule from the endogenous TF
      locus, provide conclusive proof that the cytosolic domain of TF is not essential
      for signal transduction in embryogenesis and in physiological postnatal
      processes.

PMID- 11511100
TI  - Hiv-1 Tat can substantially enhance the capacity of NIK to induce IkappaB
      degradation.
AB  - The human immunodeficiency virus type 1 (HIV-1) Tat is a virally encoded protein
      that dramatically up-regulates viral replication through interactions with the
      HIV-1 5' long terminal repeat (LTR) and cellular transcription factors. The HIV-1
      LTR is divided into three major regions: modulatory, core and TAR. The modulatory
      region contains numerous cis-acting sequences for the binding of transcription
      factors including NF-kappaB, NF-AT, and AP-1. In several reports, Tat has been
      found to induce NF-kappaB activation of the HIV-1 LTR, while in other studies Tat
      has been reported to have no effect on activation of NF-kappaB. These
      discrepancies may arise from differences in experimental conditions such as the
      source of Tat (exogenous versus endogenous), the detection methods for NF-kappaB
      activation (DNA binding capability versus IkappaB degradation), and the types of
      reporters used (HIV-1 versus non-HIV-1 derived). To reconcile these differences
      we examined the effect of endogenous Tat on NF-kappaB activation, on IkappaB
      degradation and its interaction with upstream MAP3Ks. We demonstrate that
      although an 80% reduction in Tat-induced HIV-1 LTR activity can be detected if
      the kappaB binding sites are mutated, surprisingly endogenous Tat (expressed
      intracellularly by transfection) lacks direct effect on IkappaB degradation.
      Further analysis demonstrates that although Tat alone lacks direct effect on
      IkappaBalpha degradation or dissociation from NF-kappaB, Tat can substantially
      enhance the capacity of NF-kappaB-inducing kinase (NIK), but not MEKK1, to
      accelerate degradation of IkappaB. We propose a model to explain these collective
      experimental findings.

PMID- 11511101
TI  - Il-8((3-73))K11R is a high affinity agonist of the neutrophil CXCR1 and CXCR2.
AB  - In studies aimed at developing a high affinity IL-8 antagonist, our first
      objective was to generate a high-affinity IL-8 analogue. We targeted amino acids
      within the receptor-binding domain and found that IL-8((3-73))K11R induced
      significantly more neutrophil beta-glucuronidase release than either IL-8 or the
      alternate analogues and, in chemotaxis assays, induced 2-3-fold greater
      neutrophil responses than IL-8. Furthermore, in competitive radio- or
      biotinylated-ligand binding assays, IL-8((3-73))K11R was more effective than IL
      8, IL-8((3-73)), or its T12S, H13F, and K11R/T12S/H13F analogues in blocking IL-8
      binding to neutrophils; 1.8 pmol IL-8((3-73))K11R inhibited by 50% the binding of
      approximately 20 pmol (125)I-IL-8 to neutrophils. Both IL-8 (a CXCR1/CXCR2
      ligand) and the CXCR2-specific ligand GROalpha differentially inhibited binding
      of (125)I-IL-8((3-73))K11R to neutrophils, albeit weakly, suggesting that IL-8((3
      73))K11R is a high affinity ligand for both the CXCR1 and CXCR2. Thus IL-8((3
      73))K11R is an excellent candidate for further studies aimed at generating a high
      affinity IL-8 antagonist.

PMID- 11511102
TI  - Degradation of focal adhesion proteins paxillin and p130cas by caspases or
      calpains in apoptotic rat-1 and L929 cells.
AB  - Immunofluorescence microscopy revealed the rearrangement and gradual dissociation
      of paxillin from focal adhesion sites during apoptosis. In vitro, cleavage of
      paxillin by caspase-3 generated a 42-kDa fragment, among other products, while
      cleavage by calpain generated a different set of fragments. In Rat-1 cells,
      cleavage of paxillin by caspase-3 was suppressed by zVAD-fmk or zDEVD-cmk, making
      caspase-3 a likely executioner during etoposide-induced apoptosis. In contrast,
      the cleavage of paxillin and p130cas in apoptotic L929 cells was blocked by
      calpain-specific inhibitors, which also reduced the death rate by 23 to 44%.
      Therefore, The disassembly and degradation of p130cas and paxillin during
      apoptosis may controlled by both caspases and calpains, depending upon their
      cellular contexts. Our findings also suggest that focal adhesion proteins
      paxillin and p130cas take part in integrin-mediated signaling for cell survival,
      and that their cleavage by caspase and/or calpain may not only disrupt focal
      adhesion complexes, but may also impede cell survival signaling.

PMID- 11511103
TI  - Inhibition of protein tyrosine phosphatases suppresses P-selectin exocytosis in
      activated human platelets.
AB  - P-selectin (CD62P), a cell adhesion molecule for most leukocytes, is stored in
      the alpha-granules of platelets and the Weibel-Palade bodies of endothelial
      cells. Upon thrombogenic and inflammatory challenges, P-selectin is rapidly
      expressed, by exocytosis, on activated platelets and stimulated endothelial
      cells. However, little is known with regard to the molecular mechanisms governing
      the regulation of the rapid mobilization of P-selectin in these cells. Here we
      show that phenylarsine oxide (PAO) and diamide (both were inhibitors for protein
      tyrosine phosphatases), but not genistein (an inhibitor for protein tyrosine
      kinases), adenosine, wortmannin, and LY294002 (all inhibitors for
      phosphatidylinositol 3- and 4-kinases), could inhibit P-selectin exocytosis on
      activated platelets and could abolish the P-selectin-mediated aggregation of
      activated platelets to neutrophils. However, PAO did not attenuate the P-selectin
      mediated adhesion of human promyeloid HL-60 cells on the stimulated endothelial
      cells under flow conditions. Further, PAO had no detectable effects on the
      exocytosis of P-selectin in the stimulated endothelial cells. These results
      indicate that protein tyrosine phosphatases are necessary for P-selectin
      exocytosis on the activated platelets, but not on the stimulated endothelial
      cells, and suggest that inhibitors for protein tyrosine phosphatases may be
      potentially valuable for treatment of platelet/leukocyte aggregation.

PMID- 11511104
TI  - VAP-A binds promiscuously to both v- and tSNAREs.
AB  - Proteins that bind to SNAREs may regulate their function. One such protein, VAP
      33, was first discovered in Aplysia californica and has two mammalian homologues,
      VAP-A and VAP-B. VAP-A has been implicated in vesicle targeting to the plasma
      membrane based on its location in polarized cells and its ability to bind VAMP in
      vitro. Here, we demonstrate that VAP-A is a widely expressed resident of the
      ER/Golgi intermediate compartment in COS-7 cells. Moreover, we demonstrate that
      VAMP-binding and VAP-dimerization require both the N- and C-terminal domains of
      VAP-A and also that VAP-A binds to a wide range of SNAREs and fusion-related
      proteins including syntaxin 1A, rbet1, rsec22, alphaSNAP, and NSF. Together,
      these results suggest that VAP-A is not a regulator of a specific VAMP, but
      rather may play a more general role in SNARE-mediated vesicle traffic between the
      ER and Golgi in nonpolarized cells.

PMID- 11511105
TI  - Hypoxic activation of an amiloride-sensitive cation conductance in alveolar
      epithelial cells.
AB  - Imposing hypoxia (P(O(2)) = 23 mmHg) upon A549 cells elicited increased G(amil)
      although previous work had predicted a fall in this parameter. G(amil) appeared
      to be dependent upon glucocorticoid-driven gene expression, a process inhibited
      by ERK, an enzyme activated by oxidative stress. However, hypoxia transiently
      activated this enzyme and the response was blocked by glucocorticoids, showing
      that the rise in G(amil) occurs only if ERK activation is suppressed.
      Fluorimetric assays showed that lowering P(O(2)) elicited H(2)O(2) formation
      indicating that this maneuver actually imposes oxidative stress, thus explaining
      how hypoxia can elicit responses normally associated with a rise in P(O(2)).

PMID- 11511106
TI  - Identification of a novel retrovirus long terminal repeat (LTR) that is targeted
      by p51A (TAp63gamma) and selective dominant-negative activity of p73L
      (DeltaNp63alpha) toward p53-responsive promoter activities.
AB  - The p51/p73L/p63/p40 gene, recently identified as a p53 homolog, encodes two
      major isoforms, p51A and p73L, which are suggested to have similar functions
      synonymous with p53 and dominant-negative activity toward both p53 and p51A,
      respectively. We have cloned a high affinity genomic fragment bound to p51A that
      was assigned to be a novel retrovirus long terminal repeat. Strikingly, this
      fragment was found to bind to both p53 and p73L with similar affinity to p51A.
      Additional demonstration with known p53 response elements suggested that DNA
      binding profiles of p51A and p73L were very similar but were distinct from that
      of p53. Consistent with this novel finding, transient cotransfection experiments
      in mammalian cells suggested that p73L, when it was expressed at a low level,
      selectively suppressed p53-dependent transactivation of p21-luc and mdm2-luc but
      not of cyclinG-luc and bax-luc reporters. These data raise the possibility that
      p73L differentially modulates the p53 function according to the distinct DNA
      binding affinity between these two proteins.

PMID- 11511107
TI  - Tissue-specific N-glycosylation of the ClC-3 chloride channel.
AB  - A commercially available polyclonal antibody against a rClC-3/GST fusion protein
      was used in order to investigate the tissue distribution of the ClC-3 chloride
      channel protein. The antibody appeared to be specific to rClC-3 since no cross
      reaction could be observed with rClC-4 or rClC-5 proteins when overexpressed in
      Xenopus oocytes. In mouse, mClC-3 was preferentially expressed in the central
      nervous system, intestine, and kidney. To a lower extent, mClC-3 protein was also
      detected in liver, lung, skeletal muscle, and heart. Surprisingly, the
      electrophoretic mobility of mClC-3 differed in the various tissues. After
      enzymatic digestion of N-linked oligosaccharide residues of membrane proteins
      from brain, intestine, and kidney, mClC-3 was found to migrate at its calculated
      molecular mass. This study provides important information regarding the
      specificity of the used antibody, indicates that ClC-3 is widely expressed in
      mouse, and that mClC-3 undergoes differential tissue-specific N-glycosylation.

PMID- 11511108
TI  - Potent and selective peptide agonists of alpha-melanotropin action at human
      melanocortin receptor 4: their synthesis and biological evaluation in vitro.
AB  - alpha-Melanotropin (alphaMSH) and several of its derivatives are potent but not
      selective agonists at melanocortin receptors 3, 4, and 5 present in the brain
      (MC3-5R). To differentiate between the physiological role of hMC-4R (believed to
      be involved in regulation of energy balance) from those of melanocortin receptors
      3 and 5, potent and receptor-specific agonists are needed. Therefore, the cyclic
      derivatives of alphaMSH of a general structure, cyclo(X-His-d-Phe-Arg-Trp-Y)
      NH(2), where X is succinic acid or an omega-amino-carboxylic acid, and Y is an
      alpha,omega-di-amino-carboxylic acid or an omega-carboxy-alpha-amino acid, were
      prepared and tested in binding assays and in cAMP assays on CHO cells expressing
      hMC3-5R. Several of the 21-membered or larger lactams turned out to be potent and
      hMC-4R-selective agonists. For instance, cyclo(CO-CH(2)-CH(2)-CO-His-d-Phe-Arg
      Trp-Dab)-NH(2) (Dab: 2,4-di-amino-butyric acid) was a potent agonist at hMC-4R
      (EC(50) = 4 nM) with 55-fold selectivity over hMC-3R and greater than 1000-fold
      selectivity over hMC-5R. Another potent and selective compound was cyclo(NH-CH(2)
      CH(2)-CO-His-d-Phe-Arg-Trp-Glu)-NH(2): EC(50) about 1 nM at hMC-4R, with 90-fold
      selectivity over hMC-3R and greater than 2000-fold selectivity over hMC-5R.

PMID- 11511109
TI  - Pituitary adenylate cyclase-activating polypeptide enhances Ca(2+)-dependent
      neurotransmitter release from PC12 cells and cultured cerebellar granule cells
      without affecting intracellular Ca(2+) mobilization.
AB  - The effects of pituitary adenylate cyclase-activating polypeptide (PACAP), a
      neuropeptide isolated from mammalian hypothalamus, was investigated on
      neurotransmitter release from clonal rat pheochromocytoma PC12 cells and cultured
      rat cerebellar granule cells. We found that PACAP38 stimulates the
      neurotransmitter release from PC12 cells by two distinct mechanisms in different
      concentration ranges. In the lower concentration range (<1 nM), PACAP38 enhanced
      depolarization- and ionomycin-dependent dopamine release without mobilizing
      intracellular Ca(2+), while in the higher concentration range (>1 nM), PACAP38
      induced profound Ca(2+) influx and concomitant dopamine release from PC12 cells.
      In cultured rat cerebellar granule cells, PACAP38 failed to increase
      intracellular Ca(2+); however, it enhanced depolarization-dependent glutamate
      release remarkably. These results indicate that PACAP38 enhances Ca(2+)-dependent
      neurotransmitter release by modulating step(s) subsequent to Ca(2+) entry.

PMID- 11511110
TI  - Molecular characterization of the 56-kDa CYP153 from Acinetobacter sp. EB104.
AB  - CYP153 a cytochrome P450 from Acinetobacter sp. EB104 catalyzes the hydroxylation
      of unsubstituted n-alkanes. We have decided to use the CYP153 system as a model
      for mechanistic studies on regioselective n-alkane oxidation and the interaction
      of hydrophobic substrates with soluble enzymes. Here the molecular cloning of the
      CYP153 gene is reported. Single specific primer PCR was applied to yield the
      whole gene sequence via chromosomal walks. CYP153 consists of 497 amino acids
      (M(r) = 56 kDa) and thus represents an unusually long bacterial P450, containing
      all P450 typical structural elements. It constitutes the new P450 family CYP153.
      The prolonged N-terminus of about 90 amino acids does not contain a so far known
      membrane-anchoring sequence but a 28-amino acid long amphipathic helix. The
      relevance of the remarkably long N-terminus and of other sequence motives like
      the hydrophobic F-G loop is discussed with respect to substrate binding and
      recognition.

PMID- 11511111
TI  - MPP(+) downregulates mitochondrially encoded gene transcripts and their
      activities in dopaminergic neuronal cells: protective role of Bcl-2.
AB  - The effects of neurotoxins on levels of mitochondrially encoded gene transcripts
      in a dopaminergic neuronal cell line, MN9D, were examined following treatment
      with 200 microM N-methyl-4-phenylpyridinium (MPP(+)) or 6-hydroxydopamine (6
      OHDA). As confirmed by a Northern blot analysis, levels of cytochrome c oxidase
      subunit 3 (COX III) and ATPase subunit 6 (ATPase 6) transcript were decreased in
      a time-dependent manner following treatment with MPP(+) but not with 6-OHDA.
      Accordingly, enzymatic activity of cytochrome c oxidase (COX) and the
      intracellular ATP content were also decreased in MPP(+)-treated cells while these
      remained unaltered in 6-OHDA-treated cells. In the cell death paradigm induced by
      MPP(+), overexpression of Bcl-2 in MN9D cells (MN9D/Bcl-2) significantly blocked
      MPP(+)-induced downregulation of COX III and ATPase 6 transcripts. In MN9D/Bcl-2
      cells, MPP(+)-induced downregulation of COX activity and the intracellular level
      of ATP was also blocked. Treatment with a pan-caspase inhibitor, however, neither
      prevented MPP(+)-induced downregulation of COX activity nor affected
      intracellular level of ATP in MN9D cells. Taken together, our present data
      suggest that Bcl-2 may play a regulatory role in energy metabolism by preventing
      downregulation of mitochondrially encoded gene(s) at a point distinct from its
      known anticaspase activity in MPP(+)-induced dopaminergic neuronal death.

PMID- 11511112
TI  - What is the role of cardiac PET in patients with ischaemic heart disease and
      significant left ventricular dysfunction?

PMID- 11511113
TI  - Why is there so much geographic variation in clinical outcome in international
      trials of fibrinolytic therapy?

PMID- 11511114
TI  - Is there a future for coronary physiological evaluation in clinical decision
      making?

PMID- 11511115
TI  - Prothrombotic markers in atrial fibrillation: what is new?

PMID- 11511116
TI  - Electron beam CT scanning: finding more than calcium.

PMID- 11511117
TI  - Diagnosis and management of aortic dissection.

PMID- 11511118
TI  - Patients, families and populations at high risk for coronary heart disease.

PMID- 11511119
TI  - Positron emission tomography using(18)F-fluoro-deoxyglucose and euglycaemic
      hyperinsulinaemic glucose clamp: optimal criteria for the prediction of recovery
      of post-ischaemic left ventricular dysfunction. Results from the European
      Community Concerted Action Multicenter study on use of(18)F-fluoro-deoxyglucose
      Positron Emission Tomography for the Detection of Myocardial Viability.
AB  - AIMS: To assess the accuracy of positron emission tomography to predict recovery
      of global cardiac function after revascularization in patients with coronary
      artery disease. METHODS AND RESULTS: One hundred and seventy-eight patients (157
      male, 58+/-10 years) with coronary artery disease and left ventricular
      dysfunction (mean ejection fraction 39+/-14%) were enrolled in six European
      centres. They underwent a common protocol for the assessment of viability
      using(18)F-fluoro-2-deoxyglucose (FDG) positron emission tomography during a
      standardized euglycaemic hyperinsulinaemic glucose clamp before revascularization
      by either surgery (n=140) or angioplasty (n=38). Seven patients were excluded
      because of incomplete revascularization of a dysfunctional region. Based on the
      recovery of global ejection fraction 2-6 months after revascularization, patients
      were classified into two groups: 82 patients who had a >5% improvement in
      ejection fraction postoperatively, and 89 patients without postoperative ejection
      fraction improvement. Optimal cut-off points for postoperative improvement of
      global cardiac function were computed, using receiver operating curve analysis.
      The highest sensitivity (79%) and specificity (55%) for predicting postoperative
      ejection fraction improvement by positron emission tomography was found when
      three or more dysfunctional segments had a relative FDG uptake >45% of normal
      remote myocardium (overall accuracy 67%). CONCLUSIONS: In a large cohort of
      coronary patients with impaired ejection fraction, FDG positron emission
      tomography demonstrated high sensitivity and moderate specificity to predict
      improvement of cardiac function after coronary revascularization.

PMID- 11511120
TI  - Geographic variation in patient and hospital characteristics, management, and
      clinical outcomes in ST-elevation myocardial infarction treated with
      fibrinolysis. Results from InTIME-II.
AB  - AIMS: We examined the geographic variations in InTIME-II, a randomized double
      blind trial comparing alteplase with lanoteplase for myocardial infarction.
      METHODS AND RESULTS: We compared baseline characteristics, management, and
      outcomes in four regions (Western Europe, Eastern Europe, North America, and
      Latin America) and in countries with historically different management approaches
      (Germany vs the U.K., the U.S. vs Canada). Thirty-day mortality in Western
      Europe, Eastern Europe, North America and Latin America was 6.7%, 7.3%, 5.7%,
      10.1%, P<0.0001. Adjusted mortality for Europe was intermediate between North
      America and Latin America (odds ratios (OR) [95% confidence intervals (CI)]
      compared to Western Europe: North America 0.84 [0.67-1.0], Eastern Europe 1.2
      [1.0-1.4], and Latin America 1.8 [1.3-2.7]). Revascularization rates varied 10
      fold but did not explain regional mortality differences. Germany and the U.K. had
      similar adjusted 1-year mortality (OR for the U.K. 1.16 [0.92-1.5]), although
      invasive procedures were four- to 10-fold more common in Germany. Similarly the
      U.S. and Canada had equal adjusted 1-year mortality (OR for Canada 0.85 [0.61
      1.17]) despite three-fold higher use of invasive procedures in the U.S.
      CONCLUSIONS: Significant geographic variations in practice and adjusted mortality
      following fibrinolysis persist despite recent guidelines. These findings have
      important implications in the design and interpretation of international studies,
      identify under- and over-utilized therapies, and support further study of
      treatments with marked worldwide variations.

PMID- 11511121
TI  - A synthetic factor-Xa inhibitor (ORG31540/SR9017A) as an adjunct to fibrinolysis
      in acute myocardial infarction. The PENTALYSE study.
AB  - BACKGROUND: ORG31540/SR90107A, a synthetic pentasaccharide, is a selective
      inhibitor of factor-Xa. It was hypothesized that prolonged factor-Xa inhibition
      with pentasaccharide may be an effective and safe antithrombotic co-therapy in
      acute myocardial infarction. METHODS AND RESULTS: Patients (n=333) with evolving
      ST-segment elevation acute myocardial infarction were treated with aspirin and
      alteplase and randomized to unfractionated heparin, given intravenously during 48
      to 72 h, or to a low, medium or high dose of pentasaccharide, administered daily
      for 5 to 7 days, intravenously on the first day, then subcutaneously. Coronary
      angiography was performed at 90 min and on days 5 to 7. Thrombolysis in
      Myocardial Infarction (TIMI) flow grade 3 rates at 90 min were similar in the
      four treatment groups. Among patients with TIMI 3 flow at 90 min and who did not
      undergo a coronary intervention (n=155), a trend towards less reocclusion of the
      infarct-related vessel on days 5 to 7 was observed with pentasaccharide: 0.9% vs
      7.0% with unfractionated heparin (P=0.065). Also, fewer revascularizations during
      the 30-day follow-up period were performed in patients given pentasaccharide (39%
      vs 51% for unfractionated heparin;P=0.054). The primary safety end-point, the
      combined incidence of intracranial haemorrhage and need for blood transfusion,
      was identical with pentasaccharide and unfractionated heparin (7.1%). One non
      fatal intracranial haemorrhage occurred in the 241 patients given pentasaccharide
      (0.4%). CONCLUSIONS: In this study, pentasaccharide given together with alteplase
      was safe and as effective as unfractionated heparin in restoring coronary artery
      patency. Prolonged administration of pentasaccharide was associated with a trend
      towards less reocclusion and fewer revascularizations. Selective factor-Xa
      inhibition seems to be an attractive therapeutic concept in patients presenting
      with ST-segment elevation acute myocardial infarction.

PMID- 11511122
TI  - The immediate and long-term effect of optimal balloon angioplasty on the absolute
      coronary blood flow velocity reserve. A subanalysis of the DEBATE study. Doppler
      Endpoints Balloon Angioplasty Trial Europe.
AB  - BACKGROUND: There are limited data regarding the immediate and long-term effect
      of balloon angioplasty on the coronary flow reserve evaluated in a multicentre
      setting. METHODS AND RESULTS: A total of 86 patients with one-vessel disease and
      normal left ventricular function were analysed before and after optimal balloon
      angioplasty (diameter stenosis <35%) and at 6-month follow-up. Coronary flow
      reserve was assessed with a Doppler guide wire. A low coronary flow reserve
      (<or=2.5) after PTCA, due to an increased baseline blood flow velocity, was
      encountered in 42 of the 86 patients (49%). Recurrence of angina and target
      lesion revascularization were more frequent in these patients than in patients
      with a coronary flow reserve >2.5 (46% vs 23% and 36% vs 16%, respectively;
      P<0.05) due to a trend towards restenosis (29% vs 16%; P=0.15) or a low coronary
      flow reserve at follow-up due to persistent elevated baseline blood flow
      velocity. Patients without restenosis showed a decrease or increase of coronary
      flow reserve during follow-up, determined by alterations of hyperaemic blood flow
      velocity. CONCLUSIONS: Patients with an impaired coronary flow reserve directly
      after optimal balloon angioplasty showed a higher target lesion revascularization
      rate compared to patients with a coronary flow reserve >2.5. This patient group
      consists of patients prone to develop restenosis, while other patients are
      characterized by a persistently low coronary flow reserve, probably secondary to
      disturbed autoregulation and/or diffuse mild coronary atherosclerosis. Coronary
      flow reserve alterations in patients without restenosis were related to changes
      in hyperaemic blood flow velocity, suggesting that this phenomenon relates to
      epicardial remodelling.

PMID- 11511123
TI  - Evolution of percutaneous transluminal coronary angioplasty in Europe from 1992
      1996.
AB  - BACKGROUND: The working group Coronary Circulation of the European Society of
      Cardiology has been conducting a yearly survey on coronary interventions in
      Europe. The purpose of this study is to present the evolution of percutaneous
      transluminal coronary angioplasty (PTCA) with epidemiological and economic
      implications. METHODS: Coronary interventions were polled by questionnaires
      distributed to all institutions performing cardiac catheterization. Aggregated
      country data of the years 1992-1996 on indication, type of procedure, technique,
      and outcome of coronary interventions were analysed. RESULTS: Population-adjusted
      coronary angiographies and PTCA procedures increased by 76% and by 105%,
      respectively. The Percentage of coronary stenting increased from zero to almost
      half of all procedures. Analysis per country groups reveals considerable
      variation, ranging, e.g. for PTCA in 1996 from 157 procedures per million
      population in a group of eastern countries to 1138 in a central European group.
      Relating total revascularization (R) to standardized death rate for ischaemic
      heart disease (SDR) and to gross domestic product (GDP), there was an increase
      from 1.0 to 1.8 R/SDR and 40 to 61 R/GDP in the central European group compared
      with an increase from 0.06 to 0.18 R/SDR and 43 to 85 R/GDP in the eastern group.
      CONCLUSIONS: An overall increase in PTCAs at an annual rate between 15 and 25%
      was observed. The wide variation in the use of PTCA in Europe appears to be
      dependent mostly on economic factors and national health care policies.

PMID- 11511124
TI  - Plasma von Willebrand factor, fibrinogen and soluble P-selectin levels in
      paroxysmal, persistent and permanent atrial fibrillation. Effects of
      cardioversion and return of left atrial function.
AB  - BACKGROUND: Atrial fibrillation is associated with increased risk of stroke and
      thromboembolism, possibly by conferring a prothrombotic or hypercoagulable state.
      However, it is unclear whether or not this differs in the clinical subgroups of
      chronic atrial fibrillation patients, that is, in those with paroxysmal,
      persistent or permanent atrial fibrillation. We therefore hypothesized that: (i)
      there are differences in the prothrombotic state between these patients; and (ii)
      reduction in indices of hypercoagulability would follow elective electrical
      cardioversion of persistent atrial fibrillation and the return of left atrial
      function. PATIENTS AND METHODS: We studied 69 patients with chronic atrial
      fibrillation: 23 with paroxysmal atrial fibrillation (16 males; mean age 65
      years+/-SD 13); 23 with persistent atrial fibrillation (16 males; 65 years+/-13),
      with a mean duration of atrial fibrillation of 3 months (range 2 to 6 months);
      and 23 with permanent atrial fibrillation (16 males; 67 years+/-10). Blood
      results were compared to 20 age- and sex-matched healthy controls. The patients
      with persistent atrial fibrillation then underwent elective DC cardioversion,
      with Doppler echocardiographic examinations and bloods tests performed prior to
      cardioversion, and at 3 and 12 weeks afterwards. The prothrombotic state was
      quantified by measurement of plasma levels of fibrinogen, soluble P-selectin (an
      index of platelet activation) and von Willebrand factor (a marker of endothelial
      dysfunction). RESULTS: Permanent atrial fibrillation was associated with
      significantly raised levels of von Willebrand factor, soluble P-selectin and
      fibrinogen (all P<0.001); paroxysmal atrial fibrillation with significantly
      elevated levels of plasma von Willebrand factor (P=0.0067) and fibrinogen
      (P=0.0001) but not soluble P-selectin (P=0.472); and persistent atrial
      fibrillation with normal levels of fibrinogen, von Willebrand factor and soluble
      P-selectin when compared to healthy controls (all P=ns). Stepwise multiple
      regression analyses demonstrated that the presence of atrial fibrillation was an
      independent predictor of abnormal von Willebrand factor, fibrinogen and soluble P
      selectin levels. Electrical cardioversion of the patients with persistent atrial
      fibrillation did not significantly alter levels of von Willebrand factor
      (P=0.766), soluble P-selectin (P=0.726) or fibrinogen (P=0.50) despite
      maintenance of sinus rhythm and a significant return of left atrial systolic
      function (as quantified by the presence of A wave on Doppler echocardiography) at
      3 months. CONCLUSION: There were significant differences in the prothrombotic
      state when patients with paroxysmal and permanent atrial fibrillation are
      compared to matched patients with persistent atrial fibrillation or controls in
      sinus rhythm. Cardioversion of persistent atrial fibrillation did not
      significantly alter indices of hypercoagulability even after 3 months maintenance
      of sinus rhythm, despite the return of atrial systole.

PMID- 11511125
TI  - Prevalence and clinical significance of accidental findings in electron-beam
      tomographic scans for coronary artery calcification.
AB  - AIMS: To analyse the prevalence, and diagnostic and therapeutic consequences, of
      accidental findings in electron-beam tomographic scans performed for evaluation
      of coronary artery calcification. METHODS AND RESULTS: A total of 1812
      consecutive patients with known or suspected coronary artery disease underwent
      electron-beam tomography. In 583 (32%) of the patients, i.v. contrast was also
      administered for non-invasive coronary angiography. A total of 2055 non-coronary
      pathological findings were observed in 953 (53%) of the patients. The prevalence
      of extra-cardiac disease, as shown in native scans and contrast studies, was
      assessed separately. In 583 (32%) patients, cardiac structures or the pericardium
      were affected, in 423 (23%) aortic disease was found. Lung disease was found in
      357 (20%), and pathology of other organs in 273 patients (15%). The most frequent
      findings were aortic calcium in 423 (23%) patients and heart valve calcification
      in 317 patients (17%). Malignant disease could be detected in three patients.
      Further diagnostic investigations were done in 191 (11%) patients, 141 (74%) of
      which concerned the heart. In 22 (1.2%) patients, specific therapy was initiated
      following electron-beam tomographic findings. CONCLUSION: Accidental non-coronary
      pathology is a frequent finding in electron-beam tomographic calcium scanning,
      and often requires diagnostic or therapeutic action. Profound knowledge of the
      radiological differential diagnosis of the thoracic organs is necessary for
      reporting electron-beam tomographic scans, in order to avoid misdiagnosis and to
      receive a high quality interpretation.

PMID- 11511127
TI  - Development of cognitive averaging: when light and light make dark.
AB  - In two experiments we studied developmental changes in reasoning about intensive
      quantities. In contrast to previous studies, color--an intensive quantity that is
      readily perceivable--was chosen as stimulus material. Children between 6 and 12
      years of age and adults predicted the mixture intensity of pairs of liquids with
      different intensities of red color, the liquid volumes in the two source glasses
      either being the same (Experiment 1) or different (Experiment 2). The data show
      that cognitive averaging in this domain develops late and slowly. An
      extensitivity bias, a strong tendency to use rules (adding in particular) that
      hold for extensive but not for intensive quantities, predominated up to the age
      of 12 years and was not totally absent in adults. Contrary to common expectation,
      children's use of the correct averaging rule became more likely when an extensive
      quantity, volume, was also varied and thus the task increased in complexity.

PMID- 11511128
TI  - Pink and blue collar jobs: children's judgments of job status and job aspirations
      in relation to sex of worker.
AB  - Past work shows that even young children know that occupations are differentially
      linked to men and women in our society. In our research, we studied whether 6-
      and 11-year-old children's (a) beliefs about job status and (b) job interests
      would be affected by the gendered nature of jobs. When asked about familiar
      occupations, children gave higher status ratings to masculine jobs and expressed
      greater interest in jobs culturally associated with their own sex. To circumvent
      the extant confounds between job gender and job status in our culture, we also
      developed a new methodology in which novel jobs were portrayed with either male
      or female workers. Older children rated novel jobs portrayed with male workers as
      having higher status than the identical jobs portrayed with female workers.
      Portrayal sex had no effect on children's own interests in these novel jobs at
      either age. Methodological, theoretical, and educational issues are discussed in
      relation to sex-role development and vocational aspirations.

PMID- 11511129
TI  - Serial reaction time learning in preschool- and school-age children.
AB  - Visuomotor sequence learning was assessed in 4- to 10-year-old children using a
      serial reaction time (SRT) task with both random and sequenced trials. One-half
      of the children received exposure to the sequence prior to performing the
      reaction time (RT) task. In Experiment 1, 7- and 10-year-old children
      demonstrated sequence-specific decreases in RT. As in the adult SRT literature,
      participants with explicit awareness of the sequence at the end of the session
      showed larger sequence-specific reaction time decrements than those without
      explicit awareness. Contrary to expectation, preexposure to the sequence did not
      reliably predict the level of awareness attained. Results from Experiment 2
      indicate that 4-year-olds also demonstrate significant sequence learning on a
      variant of the SRT task. This article provides preliminary data regarding
      developmental changes in sequential learning and the development and use of
      implicit and explicit knowledge. Age-related differences emerged primarily in
      explicit rather than implicit knowledge.

PMID- 11511130
TI  - Age-related changes in the misinformation effect.
AB  - In these experiments, we examined the relation between age-related changes in
      retention and age-related changes in the misinformation effect. Children (5- and
      6- and 11- and 12-year-olds) and adults viewed a video, and their memory was
      assessed immediately, 1 day, or 6 weeks later (Experiment 1). There were large
      age-related differences in retention when participants were interviewed
      immediately and after 1 day, but after the 6-week delay, age-related differences
      in retention were minimal. In Experiment 2, 11- and 12-year-olds and adults were
      exposed to neutral, leading, and misleading postevent information 1 day or 6
      weeks after they viewed the video. Exposure to misleading information increased
      the number of commission errors, particularly when participants were asked about
      peripheral aspects of the video. At both retention intervals, children were more
      likely than adults to incorporate the misleading postevent information into their
      subsequent verbal accounts. These findings indicate that age-related changes in
      the misinformation effect are not predicted by age-related changes in retention.

PMID- 11511131
TI  - The credibility of children's testimony: can children control the accuracy of
      their memory reports?
AB  - In previous work with adults (A. Koriat & M. Goldsmith, 1994, 1996c), it was
      shown that people can enhance the accuracy of their testimony substantially when
      they (a) are effective in monitoring the correctness of their answers, (b) are
      free to control their reporting accordingly (i.e., to decide which pieces of
      information to volunteer and which to withhold), and (c) are given incentives for
      accurate reporting. A theoretical model was developed, which specifies the
      critical role of metacognitive monitoring and control processes in mediating free
      report memory accuracy. The present study applies that model to examine the
      strategic regulation of memory accuracy by children. Three experiments indicate
      that both younger (ages 7 to 9) and older (ages 10 to 12) children can enhance
      the accuracy of their testimony by screening out wrong answers under free-report
      conditions but suggest a developmental trend in the level of memory accuracy that
      is thereby achieved. The implications of the results for the dependability of
      children's testimony in legal settings are discussed.

PMID- 11511132
TI  - Changes in interhemispheric transfer rate and the development of bimanual
      coordination during childhood.
AB  - In this study, we investigated the effect of the development of interhemispheric
      communication on age-related change in bimanual coordination. Interhemispheric
      communication was assessed by comparing the latency of a manual response to a
      visual stimulus when the hemisphere perceiving the stimulus and the hemisphere
      controlling the manual response were the same (uncrossed condition) to the
      latency when they were different (crossed condition). In the first experiment (5-
      to 10-year-old children) we used a two-choice response-time task, and in the
      second experiment (3- to 7-year-old children) we used a simple response-time
      task. In both studies, bimanual coordination was tested on a line-drawing task,
      and we compared performance on mirror and parallel movements. The crossed
      uncrossed difference decreased with age in both experiments. When estimated on
      the simple response-time task, the crossed-uncrossed difference was related to
      the difference in performance between mirror and parallel movements on the
      bimanual task. Thus, improved interhemispheric communication contributes to
      progress in bimanual coordination, especially that which requires resisting the
      attraction of mirror movements in order to rotate both hands with parallel
      movements.

PMID- 11511133
TI  - Phonological processing in reading Chinese among normally achieving and poor
      readers.
AB  - Ninety-four children in grades one to six (7 to 12 years old) in Hong Kong were
      individually administered a Chinese reading test consisting of 80 characters that
      varied in frequency (high or low) and orthographic structure (simple or complex).
      Phonological processing tasks, including short-term memory, pseudo-character
      recognition, and tone discrimination, were also administered. During reading,
      younger normal and poor readers made more semantic and visual errors, whereas
      older and normally achieving children made more phonologically related errors.
      Normally achieving readers also performed at a higher level than poor readers on
      short-term memory, pseudo-character recognition, and tone discrimination tasks.
      Phonological processing apparently plays a significant part in the development of
      reading skills in Chinese.

PMID- 11511134
TI  - Short-term memory, working memory, and inhibitory control in children with
      difficulties in arithmetic problem solving.
AB  - The relations between short-term memory, working memory, inhibitory control, and
      arithmetic word problem solution were studied in children who were poor in
      arithmetic problem solving (n = 23). The children were compared with a group of
      good problem solvers (n = 26), matched for vocabulary, age, and gender. The
      results corroborate the hypothesis of poor problem solvers' general deficit in
      inhibitory processes. They had lower scores and made more intrusion errors in a
      series of working memory tasks requiring inhibition of irrelevant information.
      The results showed that problem solving performance is related to the ability of
      reducing the accessibility of nontarget and irrelevant information in memory.
      Span tasks that imply passive storage of information showed that poor problem
      solvers were impaired when they have to retain numerical information, but they
      did not differ from children who did not have difficulty with mathematics when
      the material included words.

PMID- 11511135
TI  - Speech perception, lexicality, and reading skill.
AB  - This study examined the interaction between speech perception and lexical
      information among a group of 7-year-old children, of which 26 were poor readers
      and 36 were good readers. The children's performance was examined on tasks
      assessing reading skill, phonological awareness, pseudoword repetition, and
      phoneme identification. Although good readers showed clearly defined categorical
      perception in the phoneme identification task for both the /bif/-/pif/ and the
      /bis/-/pis/ continua, the category boundary for /bif/-/pif/ was at longer VOTs
      than the boundary for /bis/-/pis/, which characterizes the classic lexicality
      effect. Poor readers showed less sharply defined categorical perception on both
      continua. Although poor readers did not show the classic lexicality effect,
      lexicality did affect the overall rate with which phonemes were identified as /b/
      or /p/ at each VOT. These findings suggest that the lexicon may operate as a
      compensatory mechanism for resolving ambiguities in speech perception.
      Furthermore, statistical correction for group differences in phoneme
      identification made group differences in phoneme deletion disappear, suggesting
      that deficits in speech perception may play a causal role in the phonological
      core deficit associated with reading failure.

PMID- 11511136
TI  - The limitations of orthographic analogy in early reading development: performance
      on the clue-word task depends on phonological priming and elementary decoding
      skill, not the use of orthographic analogy.
AB  - Two experiments investigated the mechanisms underlying analogical transfer in the
      clue-word reading task developed by Goswami and her colleagues. Across both
      experiments, an equivalent number of "analogy" responses were made regardless of
      whether the clue word was seen or just heard. In addition, the number of
      "analogy" responses to words sharing both orthographic and phonological overlap
      with the clue words was no greater than that shown to words sharing only
      pronunciations. These results provide no evidence for the view that beginning
      readers make genuine orthographic-based analogies. Instead, the findings are
      interpreted within a framework in which phonological priming, in combination with
      the children's own partial decoding attempts based on limited orthographic
      knowledge, account for their performance on the clue-word task. It is concluded
      that the extent to which beginning readers make orthographic analogies is
      overestimated and as a consequence, theories that emphasize the importance of
      orthographic analogy as a mechanism driving the development of early reading
      skills need to be questioned.

PMID- 11511137
TI  - Hormone replacement therapy and longitudinal changes in blood pressure in
      postmenopausal women.
AB  - BACKGROUND: The incidence of hypertension in postmenopausal women exceeds that in
      age-matched men. Longitudinal studies relating hormone replacement therapy (HRT)
      to blood pressure changes are sparse. OBJECTIVE: To investigate the association
      between HRT and longitudinal changes in blood pressure in postmenopausal women.
      DESIGN: Longitudinal observational study. SETTING: Community-dwelling volunteers.
      PATIENTS: 226 healthy, normotensive postmenopausal women from the Baltimore
      Longitudinal Study of Aging with a mean (+/-SD) age of 64 +/- 10 years were
      followed for 5.7 +/- 5.3 years. Seventy-seven women used both estrogen and
      progestin, and 149 used neither. MEASUREMENTS: Lifestyle variables, blood
      pressure, and traditional cardiovascular risk factors were measured at baseline
      and approximately every 2 years thereafter. RESULTS: Systolic blood pressure at
      baseline was similar in HRT users and nonusers (133.9 +/- 16.0 mm Hg vs. 132.4 +/
      14.8 mm Hg). Over time, average systolic blood pressure increased less in HRT
      users than nonusers, independent of other cardiovascular risk factors, physical
      activity, and alcohol use. For example, HRT users who were 55 years of age at
      their first Baltimore Longitudinal Study of Aging visit experienced a 7.6-mm Hg
      average increase in systolic blood pressure over 10 years; in contrast, the
      average increase in nonusers was 18.7 mm Hg. The lesser increase in systolic
      blood pressure in HRT users was more evident at older age. Diastolic blood
      pressure, which did not change statistically over time in either group, was not
      associated with HRT. CONCLUSION: Postmenopausal women taking HRT have a smaller
      increase in systolic blood pressure over time than those not taking HRT. This
      difference is intensified at older ages.

PMID- 11511138
TI  - Escherichia coli O157 and Salmonella infections associated with sprouts in
      California, 1996-1998.
AB  - BACKGROUND: In California, from 1996 through 1998, more than 50% of multicounty
      outbreaks with confirmed food vehicles were related to alfalfa or clover sprouts.
      OBJECTIVE: To summarize investigations of sprout-associated outbreaks. DESIGN:
      Matched case-control studies. SETTING: California. PATIENTS: Outbreak-associated
      patients and matched population controls. MEASUREMENTS: Matched odds ratios and
      95% CIs; traceback and environmental investigations of sprout and seed growers;
      and pulsed-field gel electrophoresis of isolates from patients, sprouts, and
      seeds. RESULTS: Five sprout-associated outbreaks of salmonellosis and one
      outbreak of infection with nonmotile Shiga toxin-producing Escherichia coli O157
      occurred. Six hundred patients had culture-confirmed disease, and two died. It is
      estimated that these outbreaks caused 22 800 cases of gastrointestinal illness or
      urinary tract infection. In the case-control studies, odds ratios for the
      association between illness and alfalfa sprout consumption ranged from 5.0 to
      infinity (all were statistically significant). Three sprout growers were
      implicated, and each was associated with two outbreaks. Outbreak strains of
      Salmonella were isolated from sprouts supplied by two sprout growers and from
      seeds used by the third sprout grower. CONCLUSIONS: As currently produced,
      sprouts can be a hazardous food. Seeds can be contaminated before sprouting, and
      no method can eliminate all pathogens from seeds. Seed and sprout growers should
      implement measures to decrease contamination. The general public should recognize
      the risks of eating sprouts, and populations at high risk for complications from
      salmonellosis or E. coli O157 infection should avoid sprout consumption.

PMID- 11511139
TI  - Combination therapy with pulse cyclophosphamide plus pulse methylprednisolone
      improves long-term renal outcome without adding toxicity in patients with lupus
      nephritis.
AB  - BACKGROUND: Controlled trials in lupus nephritis have demonstrated that
      cyclophosphamide therapy is superior to corticosteroid therapy alone. The long
      term effectiveness and side-effect profiles of pulse immunosuppressive regimens
      warrant further study. OBJECTIVE: To define the long-term risk and benefit of
      monthly treatment with boluses of methylprednisolone, cyclophosphamide, or both.
      DESIGN: Extended follow-up (median, 11 years) of a randomized, controlled trial.
      SETTING: U.S. government research hospital. PATIENTS: 82 patients with
      proliferative lupus nephritis. MEASUREMENTS: Rates of treatment failure (defined
      as need for supplemental immunosuppressive therapy or doubling of serum
      creatinine concentration, or death) and adverse events. RESULTS: In an intention
      to-treat survival analysis, the likelihood of treatment failure was significantly
      lower in the cyclophosphamide (P = 0.04) and combination therapy (P = 0.002)
      groups than in the methylprednisolone group. Combination therapy and
      cyclophosphamide therapy alone did not differ statistically in terms of
      effectiveness or adverse events. Of patients who completed the protocol (n = 65),
      the proportion of patients who had doubling of serum creatinine concentration was
      significantly lower in the combination group than in the cyclophosphamide group
      (relative risk, 0.095 [95% CI, 0.01 to 0.842]). CONCLUSION: With extended follow
      up, pulse cyclophosphamide continued to show superior efficacy over pulse
      methylprednisolone alone for treatment of lupus nephritis. The combination of
      pulse cyclophosphamide and methylprednisolone appears to provide additional
      benefit over pulse cyclophosphamide alone and does not confer additional risk for
      adverse events.

PMID- 11511140
TI  - Primary aldosteronism: factors associated with normalization of blood pressure
      after surgery.
AB  - BACKGROUND: Hypertension often persists after adrenalectomy for primary
      aldosteronism. OBJECTIVE: To determine factors associated with resolution of
      hypertension after adrenalectomy for primary aldosteronism. DESIGN: Retrospective
      cohort study. SETTING: Tertiary care referral center in Rochester, Minnesota.
      PATIENTS: All patients who underwent adrenalectomy for primary aldosteronism
      between 1 January 1993 and 31 December 1999. MEASUREMENTS: Preoperative plasma
      renin activity, plasma and urinary aldosterone concentrations, and adrenal
      imaging. Follow-up blood pressure, measured at a clinic visit or at home, was
      reviewed. RESULTS: 97 adrenalectomies were performed, and follow-up was available
      in 93 patients. Hypertension was resolved at follow-up (blood pressure < 140/90
      mm Hg) without use of antihypertensive agents in 31 of 93 patients (33%).
      According to a stepwise multivariable logistic regression analysis adjusted for
      duration of follow-up, resolution of hypertension was independently associated
      with family history of hypertension in no more than 1 first-degree relative (odds
      ratio [OR], 10.9; P < 0.001) and preoperative use of two or fewer
      antihypertensive agents (OR, 4.7; P = 0.005). Additional factors associated with
      resolution of hypertension based on univariate analysis included younger age,
      shorter duration of hypertension, higher preoperative ratio of plasma aldosterone
      concentration to plasma renin activity, and higher urine aldosterone level (P <
      0.05). CONCLUSIONS: Resolution of hypertension after adrenalectomy for primary
      aldosteronism is independently associated with a lack of family history of
      hypertension and preoperative use of two or fewer antihypertensive agents.

PMID- 11511141
TI  - Long-term trends in the use of complementary and alternative medical therapies in
      the United States.
AB  - BACKGROUND: Although recent research has shown that many people in the United
      States use complementary and alternative medical (CAM) therapies, little is known
      about time trends in use. OBJECTIVE: To present data on time trends in CAM
      therapy use in the United States over the past half-century. DESIGN: Nationally
      representative telephone survey of 2055 respondents that obtained information on
      current use, lifetime use, and age at first use for 20 CAM therapies. SETTING:
      The 48 contiguous U.S. states. PARTICIPANTS: Household residents 18 years of age
      and older. MEASUREMENT: Retrospective self-reports of age at first use for each
      of 20 CAM therapies. RESULTS: Previously reported analyses of these data showed
      that more than one third of the U.S. population was currently using CAM therapy
      in the year of the interview (1997). Subsequent analyses of lifetime use and age
      at onset showed that 67.6% of respondents had used at least one CAM therapy in
      their lifetime. Lifetime use steadily increased with age across three age
      cohorts: Approximately 3 of every 10 respondents in the pre-baby boom cohort, 5
      of 10 in the baby boom cohort, and 7 of 10 in the post-baby boom cohort reported
      using some type of CAM therapy by age 33 years. Of respondents who ever used a
      CAM therapy, nearly half continued to use many years later. A wide range of
      individual CAM therapies increased in use over time, and the growth was similar
      across all major sociodemographic sectors of the study sample. CONCLUSIONS: Use
      of CAM therapies by a large proportion of the study sample is the result of a
      secular trend that began at least a half century ago. This trend suggests a
      continuing demand for CAM therapies that will affect health care delivery for the
      foreseeable future.

PMID- 11511142
TI  - Update in general internal medicine.

PMID- 11511143
TI  - Migration of T cells in vivo: molecular mechanisms and clinical implications.
AB  - T cells play an important role in the pathogenesis of chronic and autoimmune
      inflammatory diseases. They are found in high numbers in involved tissues, such
      as the lamina propria of the gut in patients with Crohn disease. Modifying T-cell
      number and function may therefore be of therapeutic value. In principle, two
      mechanisms may be responsible for the development of such T-cell infiltrates: 1)
      an increased rate of T-cell immigration into involved tissues or 2) an increased
      proliferation rate, decreased T-cell death (apoptosis) rate, and prolonged
      retention of T cells already in the tissue. Based on the theory that T cells
      selectively target affected tissues through organ-specific adhesion-molecule
      pathways, current anti-adhesion-molecule therapy aims to interfere selectively
      with T-cell entry to stop tissue damage. However, the traffic of labeled T cells
      in unmanipulated animals shows that the entry of T-cell subsets into tissues is
      not organ-specific, even under conditions of differing adhesion molecule and
      chemokine receptor expression. In contrast, within various tissues, both movement
      and survival of T-cell subsets differ considerably. These observations suggest
      that the differential expression of adhesion molecules and chemokine receptors on
      T cells serves at least two functions in vivo. First, during migration of T cells
      out of the bloodstream, the different adhesion-molecule pathways provide
      redundancy, which guarantees that T-cell subsets are able to enter the different
      tissues in sufficient numbers (security). Second, adhesion molecules and
      chemokine receptors mediate T-cell interactions within the tissue that are
      characteristic for each subset and each microenvironment and determine the nature
      of the ensuing immune response (selectivity). Shifting the focus of anti-adhesion
      molecule therapy toward the T cells in diseased tissue may lead to new treatment
      options.

PMID- 11511144
TI  - The treatment of lupus nephritis: revisiting Galen.

PMID- 11511145
TI  - Sterile injection equipment to prevent HIV infection.

PMID- 11511147
TI  - Using cost-effectiveness to target cholesterol reduction.

PMID- 11511148
TI  - The tragic events of April 1996.

PMID- 11511149
TI  - Update in general internal medicine.

PMID- 11511150
TI  - Update in pulmonary disease.

PMID- 11511151
TI  - Comparison of cardiac risk indices.

PMID- 11511152
TI  - Postprandial hypotension and relation to falls in institutionalized elderly
      persons.

PMID- 11511153
TI  - Regarding the unkind death of Billie Belle.

PMID- 11511155
TI  - Novel presentation of acute myelogenous leukemia as symptomatic galactorrhea.

PMID- 11511156
TI  - Critical aortic stenosis with severe congestive heart failure.

PMID- 11511157
TI  - Factitious pheochromocytoma-like hypertensive bouts caused by the valsalva
      maneuver.

PMID- 11511158
TI  - Severe hypersensitivity associated with clopidogrel.

PMID- 11511159
TI  - Hepatocellular injury in a patient receiving pioglitazone.

PMID- 11511160
TI  - Do resistin and resistin-like molecules also link obesity to inflammatory
      diseases?.

PMID- 11511161
TI  - Death by diagnosis.

PMID- 11511165
TI  - The Cochrane Collaboration.

PMID- 11511166
TI  - Kinetic constraints for the thiolysis of 4-methyl-5-(pyrazin-2-yl)-1,2-dithiole-3
      thione (oltipraz) and related dithiole-3-thiones in aqueous solution.
AB  - This report summarizes an investigation of the reactions of biological and other
      thiols with the cancer chemopreventive oltipraz and other dithiolethiones.
      Analysis of the kinetics of reaction of 4-methyl-5-(pyrazin-2-yl)-1,2-dithiole-3
      thione (oltipraz) 1 with monothiols and dithiols in the range of 0.75-20 mM in
      aqueous 15% ethanol, at pH 7.5 (0.1 M Tris buffer) and at 37 degrees C has been
      undertaken. A plot of k(obsd) against [thiol] shows that reactions of mono- and
      dithiols are first order in thiol concentration. The dependence on pH of these
      reactions shows that the active species is the thiolate anion. Specific second
      order rate constants, k(2) (M(-1) s(-1)) for reaction of the thiolate anions with
      oltipraz have been determined to be cysteine, 0.040 +/- 0.001; 2-mercaptoethanol,
      2.0 +/- 0.02; glutathione, 0.099 +/- 0.001; mercaptoacetic acid anion, 4.0 +/-
      0.01; dithiothreitol, 1.33 +/- 0.02; 1,3-propanedithiol, 10 +/- 0.5; 1
      mercaptopropane-3-ol, 6.5 +/- 0.1; 1-mercaptopropane-2,3-diol, 1.26 +/- 0.05. A
      plot of pK(a) against log k(2) for monothiols shows a linear dependence of k(2)
      on pK(a), beta(nuc) 1.1 +/- 0.07, which accounts for most of the reportedly
      enhanced reactivity of dithiols over monothiols. The pseudo-first-order rate
      constant for the solvolysis of oltipraz has been measured as 2.2 (+/-0.2) x 10(
      8) s(-1). The kinetics of reaction of three other dithiole-3-thiones with
      glutathione has also been studied for comparison with oltipraz. The specific
      second-order rate constants, k(2) (M(-1) s(-1)) are 5-phenyl-1,2-dithiole-3
      thione, 4.7 x 10(-)(4); 5-(4-methoxyphenyl)-1,2-dithiole-3-thione, 4.1 x 10(-4);
      and 1,2-dithiole-3-thione 0.08. Important implications for the mode of biological
      action of these compounds and the nature of the putative biological targets of
      the compounds are discussed.

PMID- 11511167
TI  - Disproportionation of a model chromium(V) complex causes extensive chromium(III)
      DNA binding in vitro.
AB  - The first direct evidence for the role of Cr(V) complexes in the formation of
      potentially mutagenic Cr(III)-DNA adducts has been obtained. A model complex for
      the stabilized Cr(V) species formed in Cr(VI)-treated cells, [Cr(V)O(ehba)(2)]
      [ehba = 2-ethyl-2-hydroxybutanoato(2-)], rapidly disproportionates in HEPES
      buffers at pH 7.4 [3 Cr(V) --> 2 Cr(VI) + Cr(III)], and the formed Cr(III)
      species undergo efficient ionic binding to DNA, followed by slower covalent
      binding. The extent of Cr(III)-DNA binding significantly exceeds that caused by
      [Cr(III)(OH(2))(6)](3+) or by the Cr(III) products of Cr(VI) reductions under
      similar conditions. The Cr(III)-DNA binding can be dramatically reduced by the
      ability of the reaction medium (e.g., phosphate buffer) to form complexes with
      Cr(III) during and after the disproportionation reaction. A mechanism of Cr(III)
      DNA binding caused by Cr(V) disproportionation has been proposed on the basis of
      stoichiometric and kinetic studies.

PMID- 11511168
TI  - An improved (32)P-postlabeling assay for the sensitive detection of 8
      oxodeoxyguanosine in tissue DNA.
AB  - To use oxidative DNA lesions as biomarkers of exposure and disease in the human
      scenario, the assay should not only be sensitive but also applicable to small
      quantities of DNA that is obtained from human tissue biopsies. Previously, we
      reported a nonenrichment (32)P-postlabeling method for measuring the oxidative
      DNA lesion, 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) [Devanaboyina, U., and
      Gupta, R. C. (1996) Carcinogenesis 17, 917-924]. Here we report a substantial
      improvement of the assay by enriching 8-oxo-dGp by TLC prior to (32)P-labeling.
      Thus, unmodified nucleotides were removed by 1-directional polyethyleneimine
      (PEI)-cellulose TLC in 0.2 M formic acid. 8-Oxo-dGp, retained close to the
      origin, was eluted in 2 M triethylammonium acetate (pH 7.0), lyophilized, (32)P
      labeled, resolved by TLC, and quantitated. The 8-oxo-dG signal was found to
      increase linearly with increasing amount of DNA. Its recovery was found to be 55
      70%, as determined by using synthetic 8-oxo-dGp. Since the modified assay allowed
      using larger quantities of DNA and higher specific activity [gamma-(32)P]ATP than
      those used in the nonenrichment procedure, the signal-to-noise ratio increased to
      30-100:1 from 3-5:1. The assay has a sensitivity of detection of <1 8-oxo
      dG/10(7) nucleotides using submicrogram to microgram DNA. The 8-oxo-dG levels
      (mean +/- SE; n = 5) in the liver, lung, heart, bladder, and trachea DNA of 3
      month-old female Sprague-Dawley rats were found to be 1.05 +/- 0.24, 0.97 +/-
      0.09, 0.75 +/- 0.15, 0.79 +/- 0.15, and 1.17 +/- 0.28 per 10(6) nucleotides,
      respectively.

PMID- 11511169
TI  - The chemistry, toxicology, and identification in rat and human urine of 4-hydroxy
      5-phenyl-1,3-oxazaperhydroin-2-one: a reactive metabolite in felbamate
      bioactivation.
AB  - 4-Hydroxy-5-phenyl-1,3-oxazaperhydroin-2-one has been proposed to be a reactive
      metabolite of the anti-epileptic drug felbamate [Thompson et al. (1996) Chem.
      Res. Toxicol. 9, 1225-1229]. 4-Hydroxy-5-phenyl-1,3-oxazaperhydroin-2-one exists
      in equilibrium with 3-oxo-2-phenylpropyl aminooate, which is known to eliminate
      to generate 2-phenylpropenal. Thus, this species is postulated to be a latent
      form of the ultimate reactive metabolite, 2-phenylpropenal. The chemistry of 4
      hydroxy-5-phenyl-1,3-oxazaperhydroin-2-one is proposed to parallel that of 4
      hydroxycyclophosphamide, the bioactivated form of cyclophosphamide that undergoes
      ring-opening to aldophosphamide and subsequent elimination to afford 2-propenal
      (acrolein). The work presented here reports the chemical synthesis of 4-hydroxy-5
      phenyl-1,3-oxazaperhydroin-2-one and demonstrates that under buffered conditions
      it exists in equilibrium with 3-oxo-2-phenylpropyl aminooate. The rate-limiting
      step in the decomposition of 4-hydroxy-5-phenyl-1,3-oxazaperhydroin-2-one is the
      irreversible beta-elimination from 3-oxo-2-phenylpropyl aminooate to 2
      phenylpropenal. We have found the half-life of 4-hydroxy-5-phenyl-1,3
      oxazaperhydroin-2-one to be 4.6 +/- 0.4 h under in vitro conditions that mimic
      the physiological setting. As a consequence of the relatively long half-life of 4
      hydroxy-5-phenyl-1,3-oxazaperhydroin-2-one, we have sought evidence for the
      significance of this pathway in experimental and clinical conditions. We report
      here the observation of this metabolite in the urine of rats being treated with 3
      hydroxy-2-phenylpropyl aminooate, the esterase-mediated metabolite of felbamate,
      and in the urine of patients undergoing felbamate therapy. In addition, we have
      shown that 4-hydroxy-5-phenyl-1,3-oxazaperhydroin-2-one is toxic to cultured
      cells in a time-dependent manner, most likely as a result of its decomposition to
      2-phenylpropenal. Taken together, the data support the hypothesis that 4-hydroxy
      5-phenyl-1,3-oxazaperhydroin-2-one represents a "time-release" form of 2
      phenylpropenal capable of traveling to distal sites from its locus of
      bioactivation and thereby mediates felbamate associated toxicities.

PMID- 11511170
TI  - Enzyme-induction dependent bioactivation of troglitazone and troglitazone quinone
      in vivo.
AB  - Troglitazone (TGZ), a 2,4-thiazolidinedione antidiabetic, causes hepatotoxicity
      in 1.9% of patients. TGZ is an inducer of, and substrate for, hepatic P450 3A.
      Microsomal metabolism yields a benzoquinone (TGZQ) and reactive intermediates.
      Kassahun et al. [Kassahun et al. (2001) Chem. Res. Toxicol. 14, 62-70] have
      trapped the intermediates as thioester, thioether, and disulfide conjugates of
      glutathione and found five conjugates in rat bile. The thioether was substituted
      in the chromane moiety. We have investigated the effect of the P450 3A inducer,
      dexamethasone (DEX), on metabolism of TGZ and TGZQ in rats and assessed the
      compounds' cytotoxicity. TGZ-glucuronide and sulfonate were confirmed as
      principal biliary metabolites of TGZ (50 mg/kg, iv). Bile from noninduced animals
      also contained a TGZ-glutathione thioether adduct (ML3) but it was substituted in
      the thiazolidinedione moiety. Pretreatment with DEX (50 mg/kg/day for 3 days)
      resulted in a 2-5-fold increase in the biliary concentration of ML3 and a 2-fold
      increase in the concentration of TGZQ, which was commensurate with the induction
      of hepatic P450 3A. Three of the known glutathione-conjugated metabolites were
      also found. TGZQ (50 mg/kg, iv) was metabolized to an analogue of one of the TGZ
      glutathione thioesters and a glutathione adduct of TGZQ hydroquinone after DEX
      pretreatment. TGZ quinol glucuronide was a biliary metabolite of TGZ and TGZQ.
      Its formation would represent deactivation of TGZQ. TGZ was toxic to rat
      hepatocytes and Hep-G2 cells at concentrations exceeding 50 and 25 microM,
      respectively, after 24 h. In contrast, TGZQ was nontoxic to rat hepatocytes and
      toxic to Hep G2 cells only at concentrations exceeding 100 microM. Our results
      show that TGZQ as well as TGZ yields reactive metabolites in vivo, and that
      bioactivation is enhanced by induction of P450 3A. However, hepatotoxicity is
      unlikely to be due to either TGZQ or its metabolites.

PMID- 11511171
TI  - Metabonomic investigations into hydrazine toxicity in the rat.
AB  - The systemic biochemical effects of oral hydrazine administration (dosed at 75,
      90, and 120 mg/kg) have been investigated in male Han Wistar rats using
      metabonomic analysis of (1)H NMR spectra of urine and plasma, conventional
      clinical chemistry, and liver histopathology. Plasma samples were collected both
      pre- and 24 h postdose, while urine was collected predose and daily over a 7 day
      postdose period. (1)H NMR spectra of the biofluids were analyzed visually and via
      pattern recognition using principal component analysis. The latter showed that
      there was a dose-dependent biochemical effect of hydrazine treatment on the
      levels of a range of low molecular weight compounds in urine and plasma, which
      was correlated with the severity of the hydrazine induced liver lesions. In
      plasma, increases in the levels of free glycine, alanine, isoleucine, valine,
      lysine, arginine, tyrosine, citrulline, 3-D-hydroxybutyrate, creatine, histidine,
      and threonine were observed. Urinary excretion of hippurate, citrate, succinate,
      2-oxoglutarate, trimethylamine-N-oxide, fumarate and creatinine were decreased
      following hydrazine dosing, whereas taurine, creatine, threonine, N
      methylnicotinic acid, tyrosine, beta-alanine, citrulline, Nalpha-acetylcitrulline
      and argininosuccinate excretion was increased. Moreover, the most notable effect
      was the appearance in urine and plasma of 2-aminoadipate, which has previously
      been shown to lead to neurological effects in rats. High urinary levels of 2
      aminoadipate may explain the hitherto poorly understood neurological effects of
      hydrazine. Metabonomic analysis of high-resolution (1)H NMR spectra of biofluids
      has provided a means of monitoring the progression of toxicity and recovery,
      while also allowing the identification of novel biomarkers of development and
      regression of the lesion.

PMID- 11511172
TI  - Reactions of N,N-bis(2-chloroethyl)-p-aminophenylbutyric acid (chlorambucil) with
      2'-deoxyguanosine.
AB  - N,N-Bis(2-chloroethyl)-p-aminophenylbutyric acid (chlorambucil, 1) was allowed to
      react in the presence of 2'-deoxyguanosine (16 mM) at physiological pH (cacodylic
      acid, 50% base), and the reactions were followed by HPLC/MS/MS techniques.
      Although the predominant reaction observed was chlorambucil hydrolysis, ca. 24%
      of 1 reacted with different heteroatoms of the nucleoside. As expected, the
      principal site of 2'-deoxyguanosine alkylation was N7. Alkylation of N7 caused
      spontaneous depurination, and N-(7-guaninylethyl)-N-hydroxyethyl-p
      aminophenylbutyric acid (5) and the corresponding N7,N7-bis-adduct (6) were the
      major stable dGuo derivatives. Also several other adducts were detected and
      tentatively identified by means of MS/MS and UV. From them, the O(6-), N1-, N(2
      ), and O5'-derivatives can be biologically significant. Our results shed new
      light on DNA modifications caused by chlorambucil, which is an important
      chemotherapeutic drug and a known carcinogen.

PMID- 11511173
TI  - Bioactivation of chemopreventive selenocysteine Se-conjugates and related amino
      acids by amino acid oxidases novel route of metabolism of selenoamino acids.
AB  - Several selenocysteine Se-conjugates have been shown to possess potent
      chemopreventive activity in animal models for chemical carcinogenesis. As a
      mechanism of action, beta-elimination reactions to form chemopreventive selenols,
      ammonia, and pyruvate has been proposed. The enzymes involved in these beta
      elimination reactions, however, have been partially elucidated. Next to cysteine
      conjugate beta-lyases, as yet unidentified non-pyridoxal-5'-phosphate-dependent
      enzymes also appear to be involved in cytosolic beta-elimination reactions. In
      the present study, it was investigated whether amino acid oxidases contribute to
      the bioactivation of selenocysteine Se-conjugates. Using purified L-amino acid
      oxidase from Crotalus adamanteus as a model enzyme, significant beta-elimination
      activities were indeed observed upon incubation with Se-methylselenocysteine
      (K(m), 195 microM; k(cat), 48 min(-1)), Se-allylselenocysteine (K(m), 608 microM;
      k(cat), 34 min(-1)), Se-phenylselenocysteine (K(m), 107 microM; k(cat), 57 min(
      1)) and Se-benzylselenocysteine (K(m), 59 microM; k(cat), 13 min(-1)). For all
      selenocysteine Se-conjugates tested, the rate of pyruvate formation was
      comparable to that of hydrogen peroxide, one of the products of oxidative
      deamination. The fact that addition of catalase did not alter pyruvate formation
      indicated that the beta-elimination reaction observed was not mediated by
      selenoxidation/syn-elimination due to the hydrogen peroxide formed via the
      oxidative deamination pathway. Using D-amino acid oxidase from porcine kidney and
      D-SeCys conjugates similar results were obtained. To delineate whether mammalian
      L-amino acid oxidases are also able to catalyze beta-elimination of
      selenocysteine Se-conjugates, rat renal cytosol was fractionated and screened for
      beta-elimination and oxidative deamination activities. One of the fractions
      isolated displayed oxidative deamination activity with several amino acids and
      cysteine S-conjugates. With selenocysteine Se-conjugates as substrates, however,
      this fraction displayed both oxidative deamination and beta-elimination
      activities, when incubated in the presence of aminoxyacetic acid to block
      contribution of pyridoxal-5'-phosphate-dependent enzymes. The potential
      significance of this novel bioactivation route for the chemopreventive activity
      of selenocysteine Se-conjugates is discussed.

PMID- 11511174
TI  - Identification and quantification of tamoxifen-DNA adducts in the liver of rats
      and mice.
AB  - A new HPLC gradient system was developed for (32)P-postlabeling analysis to
      identify and quantify hepatic tamoxifen-DNA adducts of rats and mice treated with
      tamoxifen. Four stereoisomers of alpha-(N(2)-deoxyguanosinyl)tamoxifen (dG(3')(P)
      N(2)-TAM), alpha-(N(2)-deoxyguanosinyl)-N-desmethyltamoxifen (dG(3')(P)-N(2)-N
      desmethyl-TAM), and alpha-(N(2)-deoxyguanosinyl)tamoxifen N-oxide (dG(3')(P)-N(2)
      TAM N-oxide) were prepared by reacting either alpha-acetoxytamoxifen, alpha
      acetoxy-N-desmethyltamoxifen or alpha-acetoxytamoxifen N-oxide with 2'
      deoxyguanosine 3'-monophosphate, and used as standard markers for (32)P
      postlabeling/HPLC analysis. Our HPLC gradient system can separate the above 12
      nucleotide isomers as nine peaks; six peaks representing two each trans epimers
      (fr-1 and fr-2) of dG(3')(P)-N(2)-TAM, dG(3')(P)-N(2)-N-desmethyl-TAM and
      dG(3')(P)-N(2)-TAM N-oxide, and three peaks representing a mixture of two cis
      epimers (fr-3 and fr-4) of nucleotides. Tamoxifen was given to female F344 rats
      and DBA/2 mice by gavage at doses of 45 mg/kg/day and 120 mg/kg/day,
      respectively, for 7 days. Totally 15 and 17 tamoxifen-DNA adducts were detected
      in rats and mice, respectively; among them 13 adducts were observed in both rats
      and mice. trans-dG-N(2)-TAM (fr-2) and trans-dG(3')(P)-N(2)-N-desmethyl-TAM (fr
      2) were two major adducts in both animals. Except for these two adducts, trans-dG
      N(2)-TAM N-oxide (fr-2) was the third abundant adduct that accounted for 6.4% of
      the total adducts in mice, while this accounted for only 0.3% in rats. A trans
      isomer (fr-1) and cis-isomers (fr-3 and -4) of dG(3')(P)-N(2)-TAM, dG(3')(P)-N(2)
      N-desmethyl-TAM and dG(3')(P)-N(2)-TAM N-oxide were also detected as minor
      adducts in both animals except for cis-form of dG-N(2)-TAM N-oxide in rats.
      Although the administered dose for rats was 2.7-fold less than that for mice, the
      total adduct level of rats (216 adducts/10(8) nucleotides) were 3.8-fold higher
      than mice (56.2 adducts/10(8) nucleotides). Thus, these three types of tamoxifen
      adducts accounted for 95.0 and 92.5% of the total DNA adducts of the rats and
      mice, respectively. The formation of tamoxifen adducts primarily resulted from
      alpha-hydroxylation of tamoxifen.

PMID- 11511175
TI  - Detection and characterization of DNA adducts of 3-methylindole.
AB  - The pneumotoxin 3-methylindole is metabolized to the reactive intermediate 3
      methyleneindolenine which has been shown to form adducts with glutathione and
      proteins. Reported here is the synthesis, detection, and characterization of
      nucleoside adducts of 3-methylindole. Adducted nucleoside standards were
      synthesized by the reaction of indole-3-carbinol with each of the four
      nucleosides under slightly acidic conditions, which catalyze the dehydration of
      indole-3-carbinol to 3-methyleneindolenine. Following solid phase extraction, the
      individual adducts were infused via an electrospray source into an ion trap mass
      spectrometer for molecular weight determination and characterization of the
      fragmentation patterns. The molecular ions and fragmentation of the dGuo, dAdo,
      and dCyd adducts were consistent with nucleophilic addition of the exocyclic
      primary amine of the nucleosides to the methylene carbon of 3
      methyleneindolenine. The apparent chemical preference of this addition lead
      primarily to dAdo and dGuo adducts, with substantially less of the dCyd adduct
      formed. No adduct with dThd was detected. The adducts were purified by HPLC and
      subsequent NMR analysis of the dGuo and dCyd adducts confirmed the proposed
      structures. Mass spectral fragmentation of the three adducts produced primarily
      two ions which were the result of the loss of either the 3-methylindole moiety or
      the sugar. On a triple quadrupole electrospray mass spectrometer, the neutral
      loss of the sugar, [M + H - 116](+), was utilized for selected reaction
      monitoring of the calf thymus DNA adducts, formed by incubations of 3
      methylindole with various microsomes (rat liver, goat lung, and human liver). All
      three adducts were detected from each of the microsomal incubations, following
      extraction and cleavage of the DNA to the nucleoside level. The dGuo adduct was
      the primary adduct formed, with smaller amounts of the dAdo and dCyd adducts. Rat
      hepatocytes incubated with 3-methylindole produced the same three adducts, in
      approximately the same proportions, while no adducts were detected in untreated
      hepatocytes. Microsomal incubations in the presence of ([3-(2)H(3)]-methyl)indole
      confirmed the formation and identification of the adducts as well as the
      fragmentation patterns. These results demonstrate that bioactivated 3
      methylindole forms specific adducts with exogenous or intact cellular DNA, and
      indicates that 3-methylindole may be a potential mutagenic and/or carcinogenic
      chemical.

PMID- 11511176
TI  - Reactions of 2,6-dimethyl-1,3-dioxane-4-ol (aldoxane) with deoxyguanosine and
      DNA.
AB  - In a recent study, we identified several new DNA adducts of the carcinogen
      acetaldehyde, including N(2)-(2,6-dimethyl-1,3-dioxan-4-yl)deoxyguanosine (N(2)
      aldoxane-dG, 2). Our goal in this study was to investigate further the formation
      of 2 by allowing 2,6-dimethyl-1,3-dioxane-4-ol (aldoxane, 5) to react with dG and
      DNA. Aldoxane is readily formed by trimerization of acetaldehyde. The reaction of
      aldoxane with dG and DNA produced diastereomers of N(2)-aldoxane-dG (2) as
      observed in the reactions of acetaldehyde with dG and DNA, supporting the
      intermediacy of aldoxane in their formation. Unexpectedly, however, an array of
      other adducts was formed in these reactions, including 3-(2-deoxyribos-1-yl)
      5,6,7,8-tetrahydro-8-hydroxy-6-methylpyrimido[1,2-a]purine-10(3H)one (3), 2-amino
      7,8-dihydro-8-hydroxy-6-methyl-3H-pyrrolo[2,1-f]purine-4(6H)one (13), N(2)-(3
      hydroxybutylidene)dG (9), N(2)-[(2-hydroxypropyl)-6-methyl-1,3-dioxane-4-yl]dG
      (14), and N(2)-ethylidene-dG (1). Adduct 1 was the major product and was found to
      be quite stable in DNA. The adducts result from a cascade of aldehydes, e.g., 2
      butenal (crotonaldehyde, 12), 3-hydroxybutanal (7) and its dimer (2
      hydroxypropyl)-6-methyl-1,3-dioxane-4-ol (paraldol, 6), and acetaldehyde,
      produced from aldoxane under the reaction conditions. The reactions of aldoxane
      with dG and DNA were compared with those of paraldol. The paraldol reactions gave
      products resulting from reactions of dG and DNA with paraldol, 3-hydroxybutanal,
      and crotonaldehyde (adducts 3, 13, and 9) but the products of the aldoxane and
      acetaldehyde reactions (adducts 1 and 2) were not observed, indicating that
      paraldol is more stable under the reaction conditions than is aldoxane. The
      results of this study provide new insights about the formation of DNA adducts
      from aldehydes via condensation products of the latter.

PMID- 11511177
TI  - Interaction of gamma-glutamyltranspeptidase with clofibryl-S-acyl-glutathione in
      vitro and in vivo in rat.
AB  - Clofibric acid (CA) is metabolized to chemically reactive acylating products that
      can transacylate glutathione to form clofibryl-S-acyl-glutathione (CA-SG) in
      vitro and in vivo. We investigated the first step in the degradation of CA-SG to
      the mercapturic acid conjugate, clofibryl-S-acyl-N-acetylcysteine (CA-SNAC),
      which is catalyzed by gamma-glutamyltranspeptidase (gamma-GT). After gamma-GT
      mediated cleavage of glutamate from CA-SG, the product clofibryl-S-acyl
      cysteinylglycine (CA-S-CG) should undergo an intramolecular rearrangement
      reaction [Tate, S. S. (1975) FEBS Lett. 54, 319-322] to form clofibryl-N-acyl
      cysteinylglycine (CA-N-CG). We performed in vitro studies incubating CA-SG with
      gamma-GT to determine the products formed, and in vivo studies examining the
      products excreted in urine after dosing rats with CA-SG or CA. Thus, CA-SG (0.1
      mM) was incubated with gamma-GT (0.1 unit/mL) in buffer (pH 7.4, 25 degrees C)
      and analyzed for products formed by reversed-phase HPLC and electrospray mass
      spectrometry (ESI/MS). Results showed that CA-SG is degraded completely after 6 h
      of incubation leading to the formation of two products, CA-N-CG and its
      disulfide, with no detection of CA-S-CG thioester. After 36 h of incubation, only
      the disulfide remained in the incubation. Treatment of the disulfide with
      dithiothreitol led to the reappearance of CA-N-CG. ESI/LC/MS analysis of urine
      (16 h) extracts of CA-SG-dosed rats (200 mg/kg, iv) showed that CA-SG is degraded
      to CA-N-CG, CA-N-acyl-cysteine (CA-N-C) and their respective S-methylated
      products. The mercapturic acid conjugate (CA-SNAC) was found as a minor product.
      Analysis of urine extracts from CA-dosed rats (200 mg/kg, ip) resulted in the
      detection of clofibryl-N-acyl-cysteine (CA-N-C), but no evidence for the
      formation of CA-SNAC was obtained. These in vitro and in vivo experiments
      indicate that gamma-GT mediated degradation of clofibryl-S-acyl-glutathione leads
      primarily to the formation and excretion of clofibryl-N-acyl-cysteine products
      rather than the S-acyl-NAC conjugate.

PMID- 11511178
TI  - Imbalance of estrogen homeostasis in kidney and liver of hamsters treated with
      estradiol: implications for estrogen-induced initiation of renal tumors.
AB  - Reaction of endogenous catechol estrogen quinones (CE-Q) with DNA may initiate
      cancer by generation of oncogenic mutations. Treatment of male Syrian golden
      hamsters with estrogens or 4-catechol estrogens (4-CE), but not 2-CE, induces
      kidney, but not liver, tumors. The hamster provides an excellent model for
      studying activation and deactivation (protection) of estrogen metabolites in
      relation to formation of CE-Q. Several factors can unbalance estrogen
      homeostasis, thereby increasing the oxidative pathway leading to the carcinogenic
      CE-3,4-Q. Hamsters were injected with 8 micromol of estradiol (E(2)), and liver
      and kidney extracts were analyzed for 31 estrogen metabolites, conjugates, and
      depurinating DNA adducts by HPLC with electrochemical detection. Neither liver
      nor kidney contained 4-methoxyCE, presumably due to the known inhibition of
      catechol-O-methyltransferase by 2-CE. More O-methylation of 2-CE was observed in
      the liver and more formation of CE-Q in the kidney. These results suggest less
      protective methylation of 2-CE and more pronounced oxidation of CE to CE-Q in the
      kidney. To investigate this further, hamsters were pretreated with L
      buthionine(S,R)-sulfoximine to deplete glutathione levels and then treated with
      E(2). Compared to the liver, a very low level of CE and methoxyCE was observed in
      the kidney, suggesting little protective reductase activity. Most importantly,
      reaction of CE-3,4-Q with DNA to form the depurinating 4-hydroxyE(2)(E(1))-1
      N7Gua adducts was detected in the kidney, but not in the liver. Therefore, tumor
      initiation in the kidney appears to arise from relatively poor methylation of 2
      CE and poor reductase activity in the kidney, resulting in high levels of CE-Q.
      Thus, formation of depurinating DNA adducts by CE-3,4-Q may be the first critical
      event in the initiation of estrogen-induced kidney tumors.

PMID- 11511179
TI  - Human monomethylarsonic acid (MMA(V)) reductase is a member of the glutathione-S
      transferase superfamily.
AB  - The drinking of water containing large amounts of inorganic arsenic is a
      worldwide major public health problem because of arsenic carcinogenicity. Yet an
      understanding of the specific mechanism(s) of inorganic arsenic toxicity has been
      elusive. We have now partially purified the rate-limiting enzyme of inorganic
      arsenic metabolism, human liver MMA(V) reductase, using ion exchange, molecular
      exclusion, and hydroxyapatite chromatography. When SDS-beta-mercaptoethanol-PAGE
      was performed on the most purified fraction, seven protein bands were obtained.
      Each band was excised from the gel, sequenced by LC-MS/MS and identified
      according to the SWISS-PROT and TrEMBL Protein Sequence databases. Human liver
      MMA(V) reductase is 100% identical, over 92% of sequence that we analyzed, with
      the recently discovered human glutathione-S-transferase Omega class hGSTO 1-1.
      Recombinant human GSTO1-1 had MMA(V) reductase activity with K(m) and V(max)
      values comparable to those of human liver MMA(V) reductase. The partially
      purified human liver MMA(V) reductase had glutathione S-transferase (GST)
      activity. MMA(V) reductase activity was competitively inhibited by the GST
      substrate, 1-chloro 2,4-dinitrobenzene and also by the GST inhibitor,
      deoxycholate. Western blot analysis of the most purified human liver MMA(V)
      reductase showed one band when probed with hGSTO1-1 antiserum. We propose that
      MMA(V) reductase and hGSTO 1-1 are identical proteins.

PMID- 11511180
TI  - Locating nucleobase lesions within DNA sequences by MALDI-TOF mass spectral
      analysis of exonuclease ladders.
AB  - The location of carcinogen-modified nucleobases (DNA adducts) within DNA
      sequences is a critical factor affecting their promutagenic properties and
      persistence in DNA. We now report the use of controlled exonuclease digestion
      followed by matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry (MALDI-TOF MS) to directly map modified nucleobases within DNA. The
      DNA sequence is determined by mass spectral analysis of the DNA ladders produced
      by sequential removal of nucleotides with either 5'-->3' or 3'-->5' exonuclease.
      Individual mononucleotides are identified from the mass differences between
      adjacent peaks corresponding to singly charged ions of the products of enzymatic
      cleavage. Chemically modified nucleotides are detected and identified by their
      molecular weight. The resolution and mass accuracy of this approach are
      sufficient to identify nucleobase modifications differing in mass by as little as
      2 Da. No a priori information on the DNA sequence or adduct type is required. We
      demonstrate the general applicability of this method by sequencing synthetic
      oligonucleotides containing a range of nucleobase modifications: O(6)
      methylguanine, peroxynitrite-induced oxidative lesions (oxaluric acid, oxazolone,
      cyanuric acid), and the N(2)-guanine adduct of (+,-)-7r,8t-dihydroxy-9t,10t-epoxy
      7,8,9,10-tetrahydribenzo[a]pyrene. Sequence information is also obtained for DNA
      oligodeoxynucleotides containing O(6)-pyridyloxobutylguanine, despite the ability
      of this lesion to block 3'-phosphodiesterase.

PMID- 11511181
TI  - Hypochlorite-induced damage to nucleosides: formation of chloramines and nitrogen
      centered radicals.
AB  - Stimulated monocytes and neutrophils generate hypochlorite (HOCl) via the release
      of the enzyme myeloperoxidase and hydrogen peroxide. HOCl is a key bactericidal
      agent, but can also damage host tissue. As there is a strong link between chronic
      inflammation and some cancers, we have investigated HOCl damage to DNA bases. We
      show that reaction of HOCl with the exocyclic -NH(2) groups of cytidine,
      adenosine, and guanosine, and the ring NH groups of all bases, yields chloramines
      (RNHCl/RR'NCl). These are the major initial products. Chloramine decay can be
      accelerated by UV light and metal ions, and these reactions, together with
      thermal decomposition, give rise to nucleoside-derived nitrogen-centered
      radicals. Evidence is presented for the rapid addition of pyrimidine-derived
      nitrogen-centered radicals to another parent molecule to give dimers. Experiments
      with nucleoside mixtures show that the propensity for radical formation is
      cytidine > adenosine = guanosine > uridine = thymidine. These data are
      inconsistent with the selectivity of HOCl attack and the stability of the
      resulting chloramines, but can be rationalized if chlorine transfer between bases
      is rapid and yields the most stable chloramine, with such transfer preceding
      radical formation. Thus, though thymidine is the major initial site of chloramine
      formation, rapid chlorine atom transfer generates cytidine and adenosine
      chloramines. These reactions rationalize the preferential formation of
      chlorinated cytidine and adenosine in DNA.

PMID- 11511182
TI  - Effect of benzo-ring hydroxyl groups on site-specific mutagenesis by
      tetrahydrobenzo[a]pyrene adducts at N(6) of deoxyadenosine.
AB  - We have previously investigated the mutations induced on replication in
      Escherichia coli of the M13mp7L2 genome containing each of the eight possible
      adducts derived from the four optically active 7,8-diol 9,10-epoxide metabolites
      of benzo[a]pyrene (B[a]P) by alkylation of a specific deoxyadenosine (dAdo)
      residue at N(6). Observed mutational frequencies depended in part on the relative
      spatial orientations of the three hydroxyl groups in these adducts. To determine
      how the presence or absence of these hydroxyl groups affects mutational response,
      we have synthesized 16-mer oligonucleotides with the same sequence as one of
      those previously studied with the diol epoxide adducts, but containing B[a]P-dAdo
      adducts in which two or all three of the adduct hydroxyl groups were replaced by
      hydrogen. Transfection of the adducted M13 constructs into SOS-induced
      Escherichia coli consistently gave fewer infective centers than the control
      construct, with viabilities ranging from 8.4 to 44.9% relative to control. In
      general, decreasing the number of adduct hydroxyls decreased the total frequency
      of substitution mutations induced. For all but one of the present adducts, the
      total mutational frequency was lower than that for any of the previously reported
      diol epoxide adducts in the same sequence. Remarkably, this (9S,10R)-adduct with
      cis orientation of the dAdo residue and the 9-OH group gave the highest
      mutational frequency of all the B[a]P adducts studied in this sequence, including
      the diol epoxide adducts. With the present adducts, A --> T transversions
      predominated, with smaller numbers of A --> G transitions and even fewer A --> C
      transversions.

PMID- 11511184
TI  - Metabolism of (R)- and (S)-3-(phenylamino)propane-1,2-diol in C57BL/6- and A/J
      strain mice. Identification of new metabolites with potential toxicological
      significance to the toxic oil syndrome.
AB  - The Toxic Oil Syndrome was a massive food-borne intoxication that occurred in
      Spain in 1981. Epidemiological studies point to 3-(phenylamino)propane-1,2-diol
      (PAP) derivatives as the putative toxic agents. We report further identification
      of metabolites cleared in urine of A/J and C57BL/6 mice in which (R)- and (S)-3
      (phenylamino)propane-1,2-diol were administered intraperitoneally. This
      investigation is an extension of previous studies carried out with the racemic
      compound [Ladona, M. G., Bujons, J., Messeguer, A., Ampurdanes, C., Morato, A.,
      and Corbella, J. (1999) Chem. Res. Toxicol. 12, 1127-1137]. Both PAP enantiomers
      were extensively metabolized, and several metabolites were eliminated in urine.
      The HPLC profiles of the urine samples of both mouse strains treated with each
      enantiomer were qualitatively similar, but differences were found in a relatively
      higher proportion of several detected metabolites in mice treated with (R)-PAP
      compared with those treated with (S)-PAP. The main urine metabolite continues to
      be 2-hydroxy-3-(phenylamino)propanoic acid (1), which confirms our previous
      results obtained with rac-PAP. In addition to the detection of other metabolites
      already reported in our previous paper, interesting evidence is provided on the
      presence of 4-aminophenol and paracetamol conjugates in the urine samples from
      both mouse strains. The detection of these metabolites suggests the in vivo
      formation of quinoneimine PAP derivatives. Indeed, some quinoneimine species (11
      and 12), as well as other PAP metabolites (13) that bear modifications in the
      alkyl chain, have been tentatively identified in mouse urine. These metabolic
      findings might imply a potential toxicological significance for the Toxic Oil
      Syndrome.

PMID- 11511183
TI  - 4-hydroxynonenal induces apoptosis via caspase-3 activation and cytochrome c
      release.
AB  - We investigated the mechanism by which 4-hydroxynonenal (HNE), a major aldehydic
      product of lipid peroxidation, induces apoptosis in tumor cells. Treatment of
      human colorectal carcinoma (RKO) cells with HNE-induced poly-ADP-ribose
      polymerase (PARP) cleavage and DNA fragmentation in a dose- and time-dependent
      manner. The induction of PARP cleavage and DNA fragmentation paralleled caspase
      2, -3, -8, and -9 activation. Pretreatment of cells with an inhibitor of caspase
      3, z-DEVD-fmk, or a broad spectrum caspase inhibitor, z-VAD-fmk, abolished
      caspase activation and subsequent PARP cleavage. Constitutive expression of high
      levels of Bcl-2 protected cells from HNE-mediated apoptosis. In addition, Bcl-2
      overexpression inhibited cytochrome c release from mitochondria and subsequent
      caspase-2, -3, and -9 activation. These findings demonstrate that HNE triggers
      apoptotic cell death through a mitochondrion-dependent pathway involving
      cytochrome c release and caspase activation. Bcl-2 overexpression protected cells
      from HNE-induced apoptosis through inhibition of cytochrome c release.

PMID- 11511185
TI  - Conjugation of haloalkanes by bacterial and mammalian glutathione transferases:
      mono- and vicinal dihaloethanes.
AB  - Glutathione (GSH) transferases are generally involved in the detoxication of
      xenobiotic chemicals. However, conjugation can also activate compounds and result
      in DNA modification. Activation of 1,2-dihaloethanes (BrCH(2)CH(2)Br,
      BrCH(2)CH(2)Cl, and ClCH(2)CH(2)Cl) was investigated using two mammalian theta
      class GSH transferases (rat GST 5-5 and human GST T1) and a bacterial
      dichloromethane dehalogenase (DM11). Although the literature suggests that the
      bacterial dehalogenase does not catalyze reactions with CH(3)Cl, ClCH(2)CH(2)Cl,
      or CH(3)CHCl(2), we found a higher enzyme efficiency for DM11 than for the
      mammalian GSH transferases in conjugating CH(3)Cl, CH(3)CH(2)Cl, and
      CH(3)CH(2)Br. Enzymatic rates of activation of 1,2-dihaloethanes were determined
      in vitro by measuring S,S-ethylene-bis-GSH, the major product trapped by
      nonenzymatic reaction with the substrate GSH. Salmonella typhimurium TA 1535
      systems expressing each of these GSH transferases were used to determine
      mutagenicity. Rates of formation of S,S-ethylene-bis-GSH by the GSH transferases
      correlated with the mutagenicity determined in the reversion assays for the three
      1,2-dihaloethanes, consistent with the view that half-mustards are the mutagenic
      products of the GSH transferase reactions. Half-mustards [S-(2-haloethyl)GSH]
      containing either F, Cl, or Br (as the leaving group) were tested for their
      abilities to induce revertants in S. typhimurium, and rates of hydrolysis were
      also determined. GSH transferases do not appear to be involved in the breakdown
      of the half-mustard intermediates. A halide order (Br > Cl) was observed for both
      GSH transferase-catalyzed mutagenicity and S,S-ethylene-bis-GSH formation from
      1,2-dihaloethanes, with the single exception (both assays) of BrCH(2)CH(2)Cl
      reaction with DM11, which was unexpectedly high. The lack of substrate saturation
      seen for conjugation of dihalomethanes with GSTs 5-5 and T1 was also observed
      with the mono- and 1,2-dihaloethanes [Wheeler, J. B., Stourman, N. V., Thier, R.,
      Dommermuth, A., Vuilleumier, S., Rose, J. A., Armstrong, R. N., and Guengerich,
      F. P. (2001) Chem. Res. Toxicol. 14, 1118-1127], indicative of an inherent
      difference in the catalytic mechanisms of the bacterial and mammalian GSH
      transferases.

PMID- 11511186
TI  - Conjugation of haloalkanes by bacterial and mammalian glutathione transferases:
      mono- and dihalomethanes.
AB  - A primary route of metabolism of dihalomethanes occurs via glutathione (GSH)
      transferase-catalyzed conjugation. Mammalian theta class GSH transferases and a
      group of bacterial dichloromethane dehalogenases are able to catalyze the
      hydrolytic dehalogenation of dihalomethanes via GSH conjugation and subsequent
      formation of HCHO. Dihalomethanes have been shown to induce revertants in
      Salmonella typhimurium TA 1535 expressing theta class GSH transferases. Two
      mammalian theta class GSH transferases (rat GST 5-5 and human GST T1) and the
      bacterial dehalogenase DM11 were compared in the in vitro conjugation of CH(3)Cl
      and using in vitro assays (HCHO formation) and the S. typhimurium mutagenesis
      assay with the dihalomethanes CH(2)Cl(2), CH(2)Br(2), CH(2)BrCl, CH(2)ICl,
      CH(2)I(2), and CH(2)ClF. GSTs 5-5 and T1 had similar characteristics and
      exhibited first-order rather than Michaelis-Menten kinetics for HCHO formation
      over the range of dihalomethane concentrations tested. In contrast, the DM11
      enzyme displayed typical hyperbolic Michaelis-Menten kinetics for all of the
      compounds tested. A similar pattern was observed for the conjugation of CH(3)Cl.
      The reversion tests with S. typhimurium expressing DM11 or GST 5-5 showed a
      concentration-dependent increase in revertants for most of the dihalomethanes,
      and DM11 produced revertants at dihalomethane concentrations lower than GST 5-5.
      Collectively, the results indicate that rates of conversion of dihalomethanes to
      HCHO are not correlated with mutagenicity and that GSH conjugates are genotoxic.
      The results are compared with the conjugation and genotoxicity of haloethanes in
      the preceding paper in this issue [Wheeler, J. B., Stourman, N. V., Armstrong, R.
      N., and Guengerich, F. P. (2001) Chem. Res. Toxicol. 14, 1107-1117]. The halide
      order appears most important in the dihalomethane conjugation reactions catalyzed
      by GST 5-5 and less so in GST T1 and DM11, probably due to changes in the rate
      limiting steps.

PMID- 11511187
TI  - Human enzymes involved in the metabolic activation of carcinogenic aristolochic
      acids: evidence for reductive activation by cytochromes P450 1A1 and 1A2.
AB  - Aristolochic acid (AA), a naturally occurring nephrotoxin and rodent carcinogen,
      has recently been associated with the development of urothelial cancer in humans.
      Determining the capability of humans to metabolize AA and understanding, which
      human enzymes are involved in AA activation is important in the assessment of
      individual susceptibility. Using the nuclease P1-enhanced version of the (32)P
      postlabeling assay, we compared the ability of human, minipig and rat hepatic
      microsomal samples to activate AA to metabolites forming DNA adducts. Human
      microsomes generated AA-DNA adduct profiles reproducing those found in renal
      tissues from humans exposed to AA. Identical patterns of AA-DNA adducts were also
      observed when AA was activated by minipig and rat microsomes. Therefore,
      microsomes of both animals are suitable in vitro systems mimicking the enzymatic
      activation of AA in humans. To define the role of specific P450 enzymes and
      NADPH:P450 reductase in the activation of AA by human microsomes we investigated
      the modulation of AA-DNA adduct formation by specific inducers or selective
      inhibitors of P450s and cofactors or inhibitors of NADPH:P450 reductase. The
      inducer of P450 1A1/2, beta-naphthoflavone, significantly stimulated the levels
      of AA-DNA adducts formed by rat microsomes, but inducers of P450 2B1/2 and 2E1
      had no such effect. Furthermore, only inhibitors of the P450 1A subfamily (alpha
      naphthoflavone, furafylline) significantly decreased the amount of adducts formed
      by microsomes from humans, minipigs and rats. alpha-Lipoic acid, an inhibitor of
      NADPH:P450 reductase, inhibited adduct formation too, but to a lower extent. On
      the basis of these results, we attribute most of the microsomal activation of AA
      to P450 1A1 and 1A2, although a role of NADPH:P450 reductase cannot be ruled out.
      With purified enzymes (recombinant P450 1A1/2 and NADPH:P450 reductase) and
      microsomes from baculovirus transfected insect cells expressing recombinant human
      P450 1A1/2 and NADPH:P450 reductase, the participation of these enzymes in the
      formation of AA-DNA adducts was confirmed. These results are the first report on
      the activation of AA by human enzymes and clearly demonstrate the role of P450
      1A1, 1A2, and NADPH:P450 reductase in catalyzing the reductive activation of AA.

PMID- 11511189
TI  - Long-lived near-infrared MLCT emitters.

PMID- 11511190
TI  - Toward a molecular photochemical device: a triad for photoinduced charge
      separation based on a platinum diimine bis(acetylide) chromophore.

PMID- 11511191
TI  - Phosphacarborane chemistry. Triphosphacarboranes nido 4-CH3-7,8,9,10-P3CB7H7 and
      nido-4-CH3-11-Cl-7,8,9,10-P3CB7H6, analogues of 7,8,9,10-C4B7H11 and the first
      examples of boron clusters containing three phosphorus vertexes.

PMID- 11511192
TI  - Reversible carbon monoxide photodissociation from Cu(I) coordination compounds.

PMID- 11511193
TI  - A new metal-organic polymer with large grid acentric structure created by
      unbalanced inclusion species and its electrospun nanofibers.

PMID- 11511194
TI  - Substitution and oxidation reactions of bis(dithiolene)tungsten complexes of
      potential relevance to enzyme sites.
AB  - Structurally characterized tungstoenzymes contain mononuclear active sites in
      which tungsten is coordinated by two pterin-dithiolene ligands and one or two
      additional ligands that have not been identified. In this and prior
      investigations (Sung, K.-M.; Holm, R. H. Inorg. Chem. 2000, 39, 1275; J. Am.
      Chem. Soc. 2001, 123, 1931), stable coordination units of
      bis(dithiolene)tungsten(IV,V,VI) complexes potentially related to enzyme sites
      have been sought by exploratory synthesis. In this work, additional members of
      the sets [WL(S2C2Me2)2](2-,-) and [WLL'(S2C2Me2)2](2-,-) have been prepared and
      structurally characterized. Tungsten(IV) complexes obtained by substitution are
      carbonyl displacement products of [W(CO)2(S2C2Me2)2] and include those with the
      groups W(IV)S (4), W(IV)(O2CPh) (5), and W(IV)(2-AdQ)(CO) (Q = S (6), Se (7); Ad
      = adamantyl). Those obtained by oxidation reactions contain the groups W(V)O (9),
      W(V)(QPh)2 (Q = S (10), Se (11)), W(VI)S(OPh) (12), and W(VI)O2 (14). The latter
      two complexes were obtained from W(IV) precursors using sulfur and oxygen atom
      transfer reactions, respectively. Complexes 4 and 9 are square pyramidal; 6, 7,
      10, and 11 are distorted trigonal prismatic with cis ligands LL'; and 12 and 14
      are distorted octahedral. Complexes 4, 10, and 11 support three-membered electron
      transfer series. Attempts to oxidize 4 to the W(V)S complex results in the
      formation of binuclear [W2(mu2-S)2(S2C2Me2)4](2-) having distorted octahedral
      coordination. The 21 known functional groups WL and WLL' in mononuclear
      bis(dithiolene) complexes prepared in this and prior investigations are
      tabulated. Of those with physiological-type ligands, it remains to be seen which
      (if any) of these ligation modes are displayed by enzyme sites.

PMID- 11511195
TI  - Flexibility of CuCl4-tetrahedra in bis[cinchoninium
      tetrachlorocuprate(II)]trihydrate single crystals. X-ray diffraction and EPR
      studies.
AB  - Crystal structure of bis[cinchoninium tetrachlorocuprate(II)] trihydrate,
      [(C19H24N2O)CuCl4]2-3H2O, has been determined by X-ray diffraction at 100 K and
      reexamined at 293 K. The compound crystallizes in orthorhombic system with a
      P2(1)2(1)2(1) space group and unit cell parameters a = 15.3031(14), b =
      36.415(3), and c = 7.8341(5) A at 100 K, and Z = 4. The asymmetric unit consists
      of two (CuCl4)(2-) tetrahedral anions linked by hydrogen bonds to two doubly
      protonated cinchonine molecules and three water molecules. The tetrahedra are
      strongly flattened, to approximately D(2d) symmetry, with different deformation
      for two inequivalent (CuCl4)(2-) -ions in the asymmetric unit. The deformation of
      (CuCl4)(2-) and cinchoninium cations varies with temperature due to a
      rearrangement of the bifurcated hydrogen bond network. This is a continuous
      process observed as a monotonic variation of the EPR spectral parameters and the
      unit cell dimensions. EPR spectra show that very weak exchange coupling J(12) =
      0.0030 cm(-1) operates between Cu(2+) ions within asymmetric units, corresponding
      to the general formula of the compound, as well as between equivalent Cu(2+)
      sites of different molecules, whereas the coupling is negligible between
      inequivalent sites. The intermolecular J(12) coupling is temperature-independent
      indicating that the whole asymmetric unit behaves as a magnetic unit
      (pseudodimer) in the whole temperature range.

PMID- 11511196
TI  - Green and red light emission by upconversion from the near-IR in Yb(3+) doped
      CsMnBr3.
AB  - Direct near-IR excitation of Yb(3+) 2F(7/2)-->(2)F(5/2) levels at 10126, 10138,
      and 10596 cm(-1) in CsMnBr3:0.5%Yb(3+) leads to three types of luminescence at
      cryogenic temperatures: near-IR Yb(3+) emission and green and red upconverted
      luminescence. The green luminescence around 20 000 cm(-1) is identified as
      cooperative Yb(3+) pair upconversion. The broad red upconversion luminescence
      band centered at 14 700 cm(-1) is ascribed to the 4T(1g)-->6A(1g) transition of
      Mn(2+). Pulsed measurements indicate a sequence of ground-state absorption and
      excited-state absorption steps for the red upconversion process. One- and two
      color excitation experiments support this, and we conclude that the red
      upconversion occurs by an exchange mechanism involving Yb(3+) and Mn(2+). The
      Yb(3+) 2F(5/2)-->(2)F(7/2) near-IR emission around 10 000 cm(-1) is also observed
      after Mn(2+) excitation at 21 838 cm(-1). This is indicative of a Mn(2+) 4T(1g)-
      > Yb(3+) 2F(5/2) relaxation process, which is a potential loss process for
      upconversion efficiency.

PMID- 11511197
TI  - Electron spin resonance and electronic structure of vanadyl-porphyrin in heavy
      crude oils.
AB  - A study of vanadyl-porphyrin by electron spin resonance (ESR) was carried out
      looking for answers about the role that the central V=O ion plays when these
      kinds of molecules are present in heavy crude oils. The eigenvalues of the linear
      combination of atomic orbitals (LCAO) were obtained from the experimental values
      of g and parameters (ESR). The contributions to the molecular orbitals that
      describe the various energy levels of vanadyl ion were also obtained for the
      porphyrin species. The trends of the degree of covalent character of the metal
      ligand bonds and the length of the vanadium-oxygen chemical bond are discussed.
      It is interesting to note that the Fermi contact term, K(eff), is essentially
      constant for all samples investigated, and it was found to be independent of the
      calculated electron delocalization (1 - delta(2)) and shows only little variation
      among the three different samples of oil. The orbital energies derived from our
      ESR study qualitatively agree with those predicted from MO theory for synthetic
      vanadyl-porphyrins.

PMID- 11511198
TI  - Dicubane-like tetrameric cobalt(II)-pseudohalide ferromagnetic clusters.
AB  - Three tetrameric cobalt(II)-pseudohalide complexes have been structurally and
      magnetically characterized. Compounds 1 and 2 are isomorphous and exhibit the
      general formula [Co2(dpk-OH)(dpk-CH3O)(L)(H2O)]2A2-4H2O where dpk = di-2-pyridyl
      ketone, L = N3(-) and A = BF4(-) for 1, and L = NCO(-) and A = ClO4(-) for 2. The
      ligands dpk-OH(-) and dpk-CH3O(-) result from solvolysis and ulterior
      deprotonation of dpk in water and methanol, respectively. Both compounds exhibit
      cationic tetramers consisting of a dicubane-like core with two missing vertexes
      where the Co(II) ions are connected through end-on pseudohalide and oxo-bridges.
      A similar tetranuclear core has been found for 3 whose formula is [Co2(dpk
      OH)(dpk-CH3O)(NCO)2]2. In this case, the tetramers are neutral and exhibit a
      terminal cyanate in place of the coordinated molecule of water for 1 and 2. The
      tetrameric units for 2 and 3 represent the first examples of any kind of cubanes
      exhibiting cyanate bridges as well as the first Co(II) compounds exhibiting
      intermetallic bridges through these pseudohalide groups. Measurements of the
      magnetic susceptibility indicated the presence of ferromagnetic Co(II)-Co(II)
      interactions in the three compounds.

PMID- 11511199
TI  - Zn(II), Ni(II), Cu(II), and Fe(III) complexes of potentially bimetalating
      tris(pyridine- and imidazole-appended) picket-fence naphthylporphyrins with
      benzyl ether spacers: implications for cytochrome c oxidase active-site modeling.
AB  - Two new unsymmetrical picket-fence naphthylporphyrin ligands, 1 and 2, and
      several of their metalated porphyrinato complexes have been synthesized as
      precursor model compounds for the binuclear (Fe/Cu) cytochrome c oxidase (CcO)
      active site. 1 and 2 have a naphthylporphyrin superstructure that has been
      specifically incorporated to confer long-term configurational stability to the
      atropisomeric products. The two picket-fence porphyrin ligands also bear
      covalently linked, axially offset tris(heterocycle) coordination sites for a
      copper ion, much like that found in the native enzyme. Monometallic porphyrin
      complexes [M = Zn(II), Ni(II), Cu(II), and Fe(III)] of the pyridine-appended
      ligand 1 have been prepared and spectroscopically and magnetically characterized.
      An unusual monomeric iron(III) hydroxo porphyrin complex was isolated upon workup
      of the compound formed under ferrous sulfate/acetic acid reflux conditions. There
      is general difficulty in forming binuclear complexes of 1, which is attributed to
      the conformational flexibility of the benzyl ether type picket spacers. The
      potential of ligands such as 1 and 2 for future CcO active-site modeling studies
      is considered.

PMID- 11511200
TI  - Synthesis, characterization, and electrochemistry of cis-oxothio- and cis
      bis(thio)tungsten(VI) complexes of hydrotris(3,5-dimethylpyrazol-1-yl)borate.
AB  - The complexes TpWO2X react with sulfiding agents such as B2S3 or P4S10 to give
      the oxothio- and bis(thio)tungsten(VI) complexes TpWOSX (X = Cl(-)) and TpWS2X [X
      = Cl(-), S2PPh2(-); Tp = hydrotris(3,5-dimethylpyrazol-1-yl)borate]. The reaction
      of TpWS2Cl with (i) PPh3 in pyridine and (ii) dimethyl sulfoxide affords TpWOSCl
      in good overall yield. The chloro complexes undergo metathesis with alkali metal
      salts to yield species of the type TpWOSX and TpWS2X [X = OPh(-), SPh(-), SePh(
      ), (-)-mentholate]. The diamagnetic complexes exhibit NMR spectra indicative of
      C(1) (TpWOSX) or C(s) (TpWS2X) symmetry and IR spectra consistent with terminal
      oxo and thio ligation (nu(W=O), 940-925 cm(-1); nu(W=S) or nu(WS2), 495-475 cm(
      1)). Crystals of (R,S)-TpWOS[(-)-mentholate] are monoclinic, space group P2(1),
      with a = 11.983(2) A, b = 18.100(3) A, c = 13.859(3) A, beta = 91.60(2) degrees,
      V = 3004.6(8) A(3), and Z = 4. Crystals of TpWS2(OPh)-CH2Cl2 are orthorhombic,
      space group Pbca, with a = 16.961(4) A, b = 33.098(7) A, c = 9.555(2) A, V =
      5364(2) A(3), and Z = 8. The mononuclear, distorted-octahedral tungsten centers
      are coordinated by a tridentate Tp ligand, an alkoxy or aryloxy ligand, and two
      terminal chalcogenide ligands. The average W=O and W=S distances are 1.726(7) and
      2.125(2) A, respectively, and the O=W=S and S=W=S angles 102.9(3) and 102.9(1)
      degrees, respectively. The tungsten and sulfur X-ray absorption spectra of
      TpWOSCl and TpWS2Cl are consistent with the presence of terminal pi-bonded thio
      ligands in both complexes. The thio complexes generally undergo a reversible one
      electron reduction at potentials significantly more positive than their oxo
      analogues. The chemical, spectroscopic, and electrochemical properties of the
      complexes are heavily influenced by the presence of W=S pi frontier orbitals.

PMID- 11511201
TI  - Preparations, structures, and magnetic properties of a series of novel copper(II)
      lanthanide(III) coordination polymers via hydrothermal reaction.
AB  - The hydrothermal reaction of Ln2O3 (Ln = Er, Gd, and Sm), pyridine-2,5
      dicarboxylic acid (H2pydc), and Cu(II) reagents (CuO, Cu(OAc)2-2H2O, or CuCl2
      2H2O) with a mole ratio of 1:2:4 resulted in the formation of six polymeric
      Cu(II)-Ln(III) complexes, [(Ln2Cu3(pydc)6(H2O)12)-4H2O]n (Ln = Er (1); Ln = Gd
      (2)), [(Ln4Cu2(pydc)8(H2O)12)-4H2O]n (Ln = Sm (3); Ln = Gd (4); Ln = Er (5)), and
      [(Gd2Cu2(pydc)4(H2O)8)-Cu(pydc)2-12H2O]n (6). 1 and 2 are isomorphous and
      crystallize in triclinic space group Ponebar. Compounds 3-5 are isomorphous and
      crystallize in monoclinic space group P2(1)/c. Compound 6 crystallizes in
      triclinic space group Ponebar. Complexes 1 and 2 have one-dimensional zigzag
      chain structures and compounds 3-5 display three-dimensional wavelike polymeric
      structures, while 6 has an infinite sandwich-type structure. The different
      structures of the complexes are induced by the different forms of Cu(II)
      reagents; the reactions of Cu(OAc)2-2H2O yield high Cu/Ln ratio products 1, 2,
      and 6, while the reactions of CuO or CuCl2-2H2O/2,2'-bipyridine results in low
      Cu/Ln ratio compounds 3-5. Temperature-dependent magnetic susceptibilities for 2,
      4, and 5 were studied, and the thermal stabilities of complexes 2 and 4 were
      examined.

PMID- 11511202
TI  - Mono- and dinuclear five-coordinate cyclometalated palladium(II) compounds.
AB  - Reaction of cyclometalated halide-bridged Pd(II) complexes 1-4 with the tertiary
      triphosphine ligand (Ph2PCH2CH2)2PPh (triphos) yielded complexes
      [((Ph2PCH2CH2)2PPh-P,P,P)Pd(N(Cy)=(H)C)C6H2(C(H)=N(Cy))Pd((Ph2PCH2CH2)2PPh
      P,P,P)][ClO4]2 5, [Pd(C6H4-N=NC6H5)((Ph2PCH2CH2)2PPh-P,P,P)][ClO4] 6, and [Pd(R
      C6H3C(H)=NCy)((Ph2PCH2CH2)2PPh-P,P,P)][ClO4] (7; R = 4-CHO, 8; 3-CHO).
      Spectroscopic and analytic data suggest five-coordination on the palladium atom,
      which, for complexes 5, 6, and 7, was confirmed by X-ray crystallography. The
      geometry around palladium may be view as a distorted trigonal bipyramid, with the
      palladium, nitrogen, and terminal phosphorus atoms in the equatorial plane.
      Compound 5 is the first doubly cyclometalated palladium(II) compound with two
      pentacoordinated metal centers. The structure of 6 comprises two discrete cations
      with slightly different geometries, showing the importance of crystal packing
      forces in order to determine the coordination arrangement.

PMID- 11511203
TI  - Complexation of Cu(2+) by HETPP and the pentapeptide Asp-Asp-Asn-Lys-Ile: a
      structural model of the active site of thiamin-dependent enzymes in solution.
AB  - To obtain structural information on the active site of thiamin-dependent enzymes
      in solution, we have studied the interactions of Cu(2+) ions with 2-(alpha
      hydroxyethyl)thiamin pyrophosphate (HETPP), the pentapeptide Asp-Asp-Asn-Lys-Ile
      surrounding the thiamin pyrophosphate moiety in the transketolase enzyme, and the
      tertiary Cu(2+)-pentapeptide-HETPP system in aqueous solutions at various pH
      values. In the binary Cu(2+)-pentapeptide system around physiological pH, the
      bonding sites were the terminal NH2 group, the aspartate beta-carboxylates, and a
      deprotonated peptide nitrogen, while, in the Cu(2+)-HETPP system at the same pH,
      the Cu(II) was coordinated to the pyrophosphate group and to the pyrimidine N(1')
      atom. It is found that, in the tertiary system at physiological pH, the peptide
      bone offers three coordination sites to the metal ion, and the coordination
      sphere is completed by two additional phosphate oxygens and the nitrogen N(1') of
      the thiamin coenzyme. The stability constants in the tertiary system are higher
      than those in the simpler Cu(2+)-HETPP and Cu(2+)-peptide systems. The present
      data show that the coenzyme adopts the so-called S conformation in solution. The
      importance of our findings concerning the N(1') coordination and the S
      conformation in the tertiary system is discussed in conjunction with the role of
      HETPP as an intermediate of thiamin catalysis.

PMID- 11511204
TI  - Extremely bent cyanide coordination at a preorganized dinickel site and assembly
      of a starlike nonanuclear complex from the constrained dinickel building blocks.
AB  - An extremely bent cyanide coordination at a dinickel scaffold is reported.
      Preorganization of two nickel ions is achieved by means of a compartmental
      dinucleating pyrazolate ligand L(-), setting up a bimetallic coordination pocket
      with constrained metal-metal separation. The mixed-spin dinickel(II) complex
      [LNi2(CN)(MeCN)](ClO4)2 (1) has been characterized by X-ray diffraction. The MeCN
      bound to the high-spin nickel(II) ion can be removed or replaced by other
      ligands, e.g., by the cyanide ligand of a tetracyanonickelate(II) moiety to give
      the starlike nonanuclear complex ([LNi2(CN)]4[Ni(CN)4])(ClO4)6 (2) that contains
      four of the constrained pyrazolate-based dinickel(II) fragments grouped around a
      central tetracyanonickelate(II) unit, as revealed by X-ray crystallography.
      Spectral and electrochemical properties of 1 and 2 are reported, and the
      formation of reduced mixed-valent Ni(I)Ni(II) species is investigated by IR and
      UV/vis spectroelectrochemistry.

PMID- 11511205
TI  - Mixed-valence tetranuclear manganese single-molecule magnets.
AB  - The preparations, X-ray structures, and detailed physical characterizations are
      presented for two new mixed-valence tetranuclear manganese complexes that
      function as single-molecule magnets (SMM's): [Mn4(hmp)6Br2(H2O)2]Br2-4H2O (2) and
      [Mn4(6-me-hmp)6Cl4]-4H2O (3), where hmp(-) is the anion of 2
      hydroxymethylpyridine and 6-me-hmp(-) is the anion of 6-methyl-2
      hydroxymethylpyridine. Complex 2-4H2O crystallizes in the space group P2(1)/c,
      with cell dimensions at -160 degrees C of a = 10.907(0) A, b = 15.788(0) A, c =
      13.941(0) A, beta = 101.21(0) degrees, and Z = 2. The cation lies on an inversion
      center and consists of a planar Mn4 rhombus that is mixed-valence,
      Mn2(III)Mn2(II). The hmp(-) ligands function as bidentate ligands and as the only
      bridging ligands in 2-4H2O. Complex 3-4H2O crystallizes in the monoclinic space
      group C2/c, with cell dimensions at -160 degrees C of a = 17.0852(4) A, b =
      20.8781(5) A, c = 14.835(3) A, beta = 90.5485(8) degrees, and Z = 4. This neutral
      complex also has a mixed-valence Mn2(III)Mn2(II) composition and is best
      described as having four manganese ions arranged in a bent chain. A mu2-oxygen
      atom of the 6-me-hmp(-) anion bridges between the manganese ions; the Cl(-)
      ligands are terminal. Variable-field magnetization and high-frequency and -field
      EPR (HFEPR) data indicate that complex 2-4H2O has a S = 9 ground state whereas
      complex 3.4H(2)O has S = 0 ground state. Fine structure patterns are seen in the
      HFEPR spectra, and in the case of 2.4H(2)O it was possible to simulate the fine
      structure assuming S = 9 with the parameters g = 1.999, axial zero-field
      splitting of D/k(B) = -0.498 K, quartic longitudinal zero-field splitting of
      B4(omicron)/k(B) = 1.72 x 10(-5) K, and rhombic zero-field splitting of E/k(B) =
      0.124 K. Complex 2-4H2O exhibits a frequency-dependent out-of-phase AC magnetic
      susceptibility signal, clearly indicating that this complex functions as a SMM.
      The AC susceptibility data for complex 2-4H2O were measured in the 0.05-4.0 K
      range and when fit to the Arrhenius law, gave an activation energy of DeltaE =
      15.8 K for the reversal of magnetization. This DeltaE value is to be compared to
      the potential-energy barrier height of U/k(B) = absolute value DSz(2) = 40.3 K
      calculated for 2-4H2O.

PMID- 11511206
TI  - Isolation and detailed characterization of the trans-[(H2O)2FeCl4](-) anion:
      stabilization of novel iron(III) species by large organic cations.
AB  - 1,2-Diaminoethane (en) and FeCl3 give (enH2) [FeCl5(H2O)] (1) in concentrated
      HCl, extending the aquapentachloroferrate(III) series. For 1: C2H12N2Cl5OFe,
      orthorhombic, P2(1)2(1)2(1), a = 14.531(6) A, b = 10.772(4) A, c = 6.888(2) A, Z
      = 4. Diazabicyclo[2.2.2]octane dihydrochloride (DABCO-2HCl) and FeCl3 in
      concentrated HCl form a tetrachloroferrate(III) derivative whose subsequent
      ethanol treatment (restricted water access) results in the formation of a
      compound of composition (DABCOH2)2 [FeCl4(H2O)2]Cl3 (2). This contains the trans
      [FeCl4(H2O)2](-) anion, in which the trans-Fe-O distances are 2.049(4) A. For 2:
      C12H32N4Cl7O2Fe, orthorhombic, Pnma, a = 16.378(3) A, b = 7.3323(6) A, c =
      19.431(3) A, Z = 4. A combination of 57Fe Mossbauer spectroscopy and ac
      susceptibility data confirm uncanted 3D antiferromagnetic ground states with
      T(Neel) approximately 3.4 K for (enH2)[FeCl5(H2O)] and approximately 2.0 K for
      [DABCOH2]2[FeCl4(H2O)2]Cl3.

PMID- 11511207
TI  - [ReO(N2O2)X] complexes: "4 + 1"?
AB  - [ReO(ppme)X] (where ppme(2-) is 2,5-diazo-N,N'-dimethylhexyl-1,6
      bis(phenylphosphinate), X = Br0.3Cl0.7) has been synthesized via a substitution
      reaction and structurally characterized. The coordination geometry is a distorted
      octahedron and one phosphinate coordinates cis and the other trans to the oxo O
      atom. This coordination mode is conserved in all [ReOppmeX] complexes synthesized
      in this study. [ReO(ppme)Cl] has been prepared by a reduction/complexation
      reaction from [NH4][ReO4]. [ReO(ppme)Cl] reacts with thiocyanate and benzene
      thiolate forming [ReO(ppme)X] (X = (-)NCS, (-)SC6H5), but the one-pot synthesis
      of the respective ternary thiolate complexes from perrhenate was not successful.
      The reduction/complexation reaction of a thiol, H2ppmeCl4, and perrhenate
      resulted in the formation of [H3ppme][ReO(SR)4], the reaction of which with
      [ReO(ppme)Cl] does not lead to [ReO(ppme)SR] in high yields.

PMID- 11511208
TI  - Three-dimensional open frameworks based on cobalt(II) and nickel(II) m
      pyridinecarboxylates.
AB  - Three-dimensional open frameworks [Co2(nicotinate)4(mu-H2O)]-CH3CH2OH-H2O, 1, and
      [Ni2(nicotinate)4(mu-H2O)]-CH3CH2OH-H2O, 2, were obtained by hydro(solvo)thermal
      reactions between 3-cyanopyridine and cobalt(II) nitrate and nickel(II)
      perchlorate, respectively. Both 1 and 2 exhibit complicated 3-D structures based
      on [M2(nicotinate)4(mu-H2O)] (M = Co or Ni) building blocks and possess open
      channels that are occupied by removable solvent molecules. 3-D open frameworks
      [M2L4(mu-H2O)]-HL-(H2O)x (where M = Co, x = 2, 3, and M = Ni, x = 1, 4, and L =
      trans-3-(3-pyridyl)acrylate) were similarly prepared with trans-3-(3
      pyridyl)acrylic acid in place of 3-cyanopyridine. Compounds 3 and 4 are
      isostructural and exhibit network topologies similar to that of 1 with open
      channels occupied by disordered trans-3-(3-pyridyl)acrylic acid and water guest
      molecules. Crystal data for 1: triclinic space group Ponebar, a = 10.534(1) A, b
      = 11.907(1) A, c = 14.046(1) A, alpha = 106.645(1) degrees, beta = 101.977(1)
      degrees, gamma = 112.078(1) degrees, and Z = 4. Crystal data for 2: tetragonal
      space group P4/ncc, a = 20.089(1) A, c = 14.016(1) A, and Z = 4. Crystal data for
      3: monoclinic space group C2/c, a = 14.082(2) A, b = 15.278(2) A, c = 18.537(2)
      A, beta = 105.360(2) degrees, and Z = 2. Crystal data for 4: monoclinic space
      group C2/c, a = 14.082(1) A, b = 15.250(1) A, c = 18.606(1) A, beta = 106.747(1)
      degrees, and Z = 2.

PMID- 11511209
TI  - Rational design of three-dimensional (3D) optically active molecule-based
      magnets: synthesis, structure, optical and magnetic properties of
      ([Ru(bpy)3](2+), ClO4(-), [Mn(II) Cr(III)(ox)3](-))n and ([Ru(bpy)2ppy](+),
      [M(II)Cr(III)(ox)3](-))n, with M(II) = Mn(II), Ni(II). X-ray structure of
      ([deltaRu(bpy)3](2+), ClO4(-), [deltaMn(II)DeltaCr(III)(ox)3](-))n and
      ([lambdaRu(bpy)2ppy)](+), [lambdaMn(II)lambdaCr(III)(ox)3](-))n.
AB  - To elucidate the relation between structural and magnetic properties, we have
      synthesized molecular materials having both Cotton effects and a ferromagnetic
      long range order. Such optically active 3D molecule-based magnets were rationally
      designed using the enantioselective template effect of optically active cations,
      namely Delta or Lambda [Ru(bpy)3, ClO4](+) or Delta or Lambda [Ru(bpy)3ppy](+)
      (bpy = bipyridine; ppy = phenylpyridine). Such cations are able to template the
      formation of optically active 3D anionic networks in which transition metal ions
      (Cr-Mn) and (Cr-Ni) are connected by oxalate ligands (ox). Following this
      strategy, we described the synthesis of ([Ru(bpy)3](2+), ClO4(-),
      [Mn(II)Cr(III)(ox)3](-))n and ([Ru(bpy)2ppy](+), [M(II)Cr(III)(ox)3](-))n with
      M(II) = Mn(II), Ni(II) in their optically active forms. In these 3D networks, all
      of the metallic centers have the same configuration, Delta or Lambda, as the
      template cation. We have determined the structure of
      ([DeltaRu(bpy)3][ClO4][DeltaMnDeltaCr(ox)3])n and ([LambdaRu(bpy)2ppy](+),
      [LambdaMn(II)LambdaCr(III)(ox)3](-))n by X-ray diffraction studies. These
      optically active networks show the Cotton effect and long-range ferromagnetic
      order at low temperatures. The magnetic circular dichroism of ([Ru(bpy)3](2+),
      ClO4(-), [Mn(II)Cr(III)(ox)3](-))n at 2 K is reported.

PMID- 11511210
TI  - The effects of anion variation and ligand derivatization on silver coordination
      networks based upon weaker interactions.
AB  - This article presents a series of silver(I) coordination networks based upon
      nonchelating bidentate thioether ligands. Frameworks using AgOTs as the silver(I)
      starting material form two-dimensional frameworks and are quite stable as shown
      by differential scanning calorimetry/thermogravimetric analysis (DSC/TGA) data.
      The networks are sufficiently robust as to maintain the same layered motif when
      the basic skeleton of the ligand is sequentially derivatized with -OEt, OBu, and
      OHex groups. Crystal structures of the AgOTs complexes of the underivatized and
      bis(hexoxy) derivatives, compounds 5 and 8, respectively, are presented as well
      as powder X-ray diffraction (PXRD) data of the other complexes. For 5,
      C20H20S3O3Ag, crystal data are as follows: monoclinic, space group P2(1)/n, a =
      11.8117(5) A, b = 7.8813(5) A, c = 22.3316(10) A, beta = 102.245(5) degrees, V =
      2031.6(2) A(3), Z = 4. For 8, C30H44S3O6Ag, crystal data are as follows:
      triclinic, space group Ponebar a = 8.445(4) A, b = 10.855(5) A, c = 19.308(9) A,
      alpha = 84.53(1) degrees, beta = 78.76(1) degrees, gamma = 68.43(1) degrees V =
      1613.9(13) A(3), Z = 2. Changing the silver(I) starting material to AgPF6 results
      in a shift to a one-dimensional structure, 9, as shown by X-ray crystallography
      and in highly compromised stability. For 9, C14H16S2N2PF6Ag, crystal data are as
      follows: monoclinic, space group P2/n, a = 11.9658(11) A, b = 3.9056(4) A, c =
      19.6400(18) A, beta = 92.87(1) degrees, V = 916.70(15) A(3), Z = 4.

PMID- 11511211
TI  - Metal-to-ligand electron transfer in diiminopyridine complexes of Mn-Zn. A
      theoretical study.
AB  - A series of complexes ML2(x+) (M = Mn-Zn, L = 2,6-bis(iminomethyl)pyridine) was
      investigated by theoretical methods. Electron transfer from the metal "t(2g)"
      orbitals to the ligand pi orbitals is reflected in the elongation of ligand C-N
      bonds and shortening of the C(py)-C(imine) bonds. Using zinc complexes as
      references, these deformations could be used to quantify the number of electrons
      transferred. Strong transfer is found in low-spin MnL2(+) (ca. 2 e) and in high
      spin MnL2(+) and low-spin MnL2(2+), FeL2(2+), and CoL2(+) (ca. 1 e each). Smaller
      transfer is found in CoL(2)(2+), and the transfer is insignificant in high-spin
      MnL2(2+), NiL2(2+), and CuL2(2+). Analysis of the unpaired electron density on
      the metal (using the Staroverov-Davidson method) shows that the contribution of a
      biradical description, in which ligand radical anions are antiferromagnetically
      coupled to the metal center, is significant in most cases. In the case of CoL2(+)
      and high-spin MnL2(+), where the metal-ligand bond is weakened, it amounts to
      over 50% of the total transfer.

PMID- 11511212
TI  - Two-, three-, and four-coordination at gold(I) supported by the bidentate
      selenium ligand [Ph2P(Se)NP(Se)Ph2](-).
AB  - Treatment of the gold(I) halide complexes LAuCl (L = PMe3, PPh3, CNC6H3Me2-2,6)
      with K[Ph2P(Se)NP(Se)Ph2] provides the gold-selenium coordination compounds
      [(N(Ph2PSe)2-Se,Se')AuL]. However, on standing for a number of days, the complex
      [(N(Ph2PSe)2-Se,Se')AuPMe3] gains a phosphine to provide the bis(phosphine)
      species [(N(Ph2PSe)2-Se,Se')Au(PMe3)2]. Treatment of the K[Ph2P(Se)NP(Se)Ph2]
      ligand with [(Ph3PAu)3O]BF4 allows the isolation of [(N(Ph2PSe)2
      Se,Se')(AuPPh3)2]BF4. Reaction of the complex [(dppm)(AuCl)2] with AgSO3CF3
      followed by addition of the ligand K[Ph2P(Se)NP(Se)Ph2] results in the formation
      of [(N(Ph2PSe)2-Se,Se')Au2(dppm)]OSO2CF3 and treatment of [(tht)AuCl] (tht =
      tetrahydrothiophene) with an equimolar quantity of K[Ph2P(Se)NP(Se)Ph2] affords
      the complex [(N(Ph2PSe)2-Se,Se')2Au2]. The compounds [(N(Ph2PSe)2
      Se,Se')Au2(dppm)]OSO2CF3, [(N(Ph2PSe)2-Se,Se')AuPPh3] and [(N(Ph2PSe)2
      Se,Se')Au(PMe3)2] have been investigated crystallographically. The results reveal
      that the metal centers are two-, three-, and four-coordinate, respectively. The
      cationic, eight-membered ring complex bearing the dppm ligand displays
      transannular aurophilic bonding and is further associated into dimers via
      intermolecular gold-selenium contacts. The six-membered rings in the other two
      structures have C2-symmetrical twist conformations, however, the Au(I)
      coordination sphere in [N(PPh2Se)2]AuPPh3 is not fully symmetrical. The Au-Se
      bond lengths increase dramatically as the coordination number of the metal atom
      becomes larger.

PMID- 11511213
TI  - Synthesis and spectroscopic studies of non-heme diiron(III) species with a
      terminal hydroperoxide ligand: models for hemerythrin.
AB  - Two compounds, [Fe2(mu-OH)(mu-Ph4DBA)(TMEDA)2(OTf)] (4) and [Fe2(mu-OH)(mu
      Ph4DBA)(DPE)2(OTf)] (7), where Ph4DBA(2-) is the dinucleating bis(carboxylate)
      ligand dibenzofuran-4,6-bis(diphenylacetate), have been prepared as synthetic
      models for the dioxygen-binding non-heme diiron protein hemerythrin (Hr). X-ray
      crystallography reveals that, in the solid state, these compounds contain the
      asymmetric coordination environment found at the diiron center in the reduced
      form of the protein, deoxyHr. Mossbauer spectra of the models (4, delta =
      1.21(2), DeltaE(Q) = 2.87(2) mm s(-1); 7, delta(av) = 1.23(1), DeltaE(Qav) =
      2.79(1) mm s(-1)) and deoxyHr (delta = 1.19, DeltaE(Q) = 2.81 mm s(-1)) are also
      in good agreement. Oxygenation of the diiron(II) complexes dissolved in CH2Cl2
      containing 3 equiv of N-MeIm (4) or neat EtCN (7) at -78 degrees C affords a red
      orange solution with optical bands at 336 nm (7300 M(-1) cm(-1)) and 470 nm (2600
      M(-1) cm(-1)) for 4 and at 334 nm (6400 M(-1) cm(-1)) and 484 nm (2350 M(-1) cm(
      1)) for 7. These spectra are remarkably similar to that of oxyHr, 330 nm (6800 M(
      1) cm(-1)) and 500 nm (2200 M(-1) cm(-1)). The electron paramagnetic resonance
      (EPR) spectrum of the cryoreduced, mixed-valence dioxygen adduct of 7 displays
      properties consistent with a (mu-oxo)diiron(II,III) core. An investigation of 7
      and its dioxygen-bound adduct by extended X-ray absorption fine structure (EXAFS)
      spectroscopy indicates that the oxidized species contains a (mu-oxo)diiron(III)
      core with iron-ligand distances in agreement with those expected for oxide,
      carboxylate, and amine/hydroperoxide donor atoms. The analogous cobalt complex
      [Co2(mu-OH)(mu-Ph4DBA)(TMEDA)2(OTf)] (6) was synthesized and structurally
      characterized, but it was unreactive toward dioxygen.

PMID- 11511214
TI  - Triamidoamine complexes of chromium(III) and chromium(IV).
AB  - Treatment of [CrCl3(THF)3] with slightly more than 1 equiv of Li3(N3N) [(N3N)(3-)
      = ((Me3SiNCH2CH2)3N)(3-)] affords the triamidoamine complex [Cr(N3N)] (1) in 75%
      yield. 1 is oxidized by PhICl2, CuCl2, or AgCl to give the chromium(IV) complex
      [Cr(N3N)Cl] (2) in moderate yields. Alternatively, complex 2 is obtained directly
      from [CrCl3(THF)3] in 50% yield after treatment with 0.5 equiv of Li3(N3N). Both
      compounds are high-spin complexes bearing three and two unpaired electrons,
      respectively. Their molecular structures are described revealing a trigonal
      monopyramidal and trigonal bipyramidal coordination geometry of the chromium
      center, respectively.

PMID- 11511215
TI  - Trialkylphosphine-stabilized copper-phenyltellurolate complexes: from small
      molecules to nanoclusters via condensation reactions.
AB  - Reactions of CuCl with Te(Ph)SiMe3 and solublizing trialkylphosphine ligands
      afford a series of polynuclear copper-phenyltellurolate complexes that has been
      structurally characterized. The formation of the complexes is found to be highly
      dependent on the ancillary phosphine ligand used. The synthesis and structures of
      [Cu2(mu-TePh)2(PMe3)4] 1, [Cu4(mu3-TePh)4(PPr(i)3)3] 2, [Cu5(mu-TePh)3(mu3
      TePh)3(PEt3)3][PEt3Ph] 3, and [Cu12Te3(mu3-TePh)6(PEt3)6] 4 are described. The
      telluride (Te(2-)) ligands in 4 arise from the generation of TePh2 in the
      reaction mixtures. The subsequent co-condensation of clusters 3 and 4 leads to
      the generation of the nanometer sized complex [Cu29Te9(mu3-TePh)10(mu4
      TePh)2(PEt3)8][PEt3Ph] 5 in good yield, in addition to small amounts of [Cu39(mu3
      TePh)10(mu4-TePh)Te16(PEt3)13] 6. These complexes are formed via the photo
      elimination of TePh2. The cyclic voltammogram of 5 in THF solution exhibits two
      oxidation waves, assigned to the oxidation of the Cu(I) centers.

PMID- 11511216
TI  - Insulin-enhancing vanadium(III) complexes.
AB  - Simple, high-yield, large-scale syntheses of the V(III) complexes
      tris(maltolato)vanadium(III), V(ma)3, tris(ethylmaltolato)vanadium(III), V(ema)3,
      tris(kojato)vanadium(III) monohydrate, V(koj)3-H2O, and tris(1,2-dimethyl-3
      hydroxy-4-pyridinonato)vanadium(III) dodecahydrate, V(dpp)3-12H2O, are described;
      the characterization of these complexes by various methods and, in the case of
      V(dpp)3-12H2O, by an X-ray crystal structure determination, is reported. The
      ability of these complexes to normalize glucose levels in the STZ-diabetic rat
      model has been examined and compared with that of the benchmark compound BMOV
      (bis(maltolato)oxovanadium(IV)), an established insulin-enhancing agent.

PMID- 11511218
TI  - The encapsulation of ferrocyanide by copper(II) complexes of tripodal
      tetradentate ligands. Novel H-bonding networks incorporating heptanuclear and
      pentanuclear heterometallic assemblies.
AB  - Substitution of the weakly binding aqua ligand in [Cu(tren)OH2](2+) and
      [Cu(tpa)OH2](2+) (tren = tris(2-aminoethyl)amine; tpa = tris(2
      pyridylmethyl)amine) by a cyano ligand on ferricyanide results in the assembly of
      heteropolynuclear cations around the cyanometalate core. In water, the reduction
      of the Fe(III) core to Fe(II) generates complexes that feature heteropolycations
      in which ferrocyanide is encapsulated by the Cu(II) moieties:
      [(Cu(tpa)CN)6Fe][ClO4]8-3H2O 1, [(Cu(tren)CN)6Fe][ClO4]8-10H2O 2,
      [(Cu(tren)CN)6Fe][Fe(CN)6]2[ClO4]2-15.8H2O 3, and
      [(Cu(tren)CN)6Fe][(Cu(tren)CN)4Fe(CN)2][Fe(CN)6)]4-6DMSO-21H2O 4. The formation
      of discrete molecules, in preference to extended networks or polymeric
      structures, has been encouraged through the use of branched tetradentate ligands
      in conjunction with copper(II), a metal center with the propensity to form five
      coordinate complexes. Complex 3 crystallizes in the monoclinic space group
      P2(1)/c (#14) with a = 14.8674(10), b = 25.9587(10), c = 27.5617(10) A, beta =
      100.8300(10) degrees, and Z = 4, and it is comprised of almost spherical
      heptanuclear cations, [(Cu(tren)CN)6Fe](8+), whose charge is balanced by two
      ferricyanide and two perchlorate counteranions. Complex 4 crystallizes in the
      triclinic space group P1 (# 1) with a = 14.8094(8), b = 17.3901(7), c =
      21.1565(11) A, alpha = 110.750(3), beta = 90.206(2), gamma = 112.754(3) degrees,
      and Z = 1, and it is comprised of the heptanuclear [(Cu(tren)CN)6Fe](8+) cation
      and pentanuclear [(Cu(tren)CN)4Fe(CN)2](4+) cation, whose terminal cyano ligands
      are oriented trans to each other. The charge is balanced exclusively by
      ferricyanide counteranions. In both complexes, H-bonding interactions between
      hydrogens on primary amines of the tren ligand, terminal cyano groups of the
      ferricyanide counterions, and the solvent of crystallization generate intricate
      3D H-bonding networks.

PMID- 11511217
TI  - Low-valent chemistry of cobalt amide. Synthesis and structural characterization
      of cobalt(II) amido, aryloxide, and thiolate compounds.
AB  - The binuclear cobalt(II) amide complex [(CoL2)2-(TMEDA)] (1) [L = N(Si(t)BuMe2)(2
      C5H3N-6-Me); TMEDA = Me2NCH2CH2NMe2] has been synthesized by the reaction of
      anhydrous CoCl2 with 2 equiv of [Li(L)(TMEDA)]. X-ray crystallography revealed
      that complex 1 consists of two [CoL2] units linked by one TMEDA ligand molecule,
      which binds in an unusual N,N'-bridging mode. Protolysis of 1 with the bulky
      phenol Ar(Me)OH (Ar(Me) = 2,6-(t)Bu2-4-MeC6H2) and thiophenol ArSH (Ar = 2,4,6
      (t)Bu3C6H2) gives the neutral monomeric cobalt(II) bis(aryloxide)
      [Co(OAr(Me))2(TMEDA)] (2) and dithiolate [Co(SAr)2(TMEDA)] (3), respectively.
      Complexes 1-3 have been characterized by mass spectrometry, microanalysis,
      magnetic moment, and melting-point measurements, in addition to X-ray
      crystallography.

PMID- 11511219
TI  - Benzo[2,1-c:3,4-c']bis(1,2,3-thiaselenazole) (BSe) and its charge trasfer
      chemistry. Crystal and electronic structure of [BSe]3[ClO4]2.
AB  - The S-Se-N-based heterocycle benzo[2,1-c:3,4-c']bis(1,2,3-thiaselenazole) (BSe)
      can be prepared by the condensation of 1,4-diaminobenzene-2,3-dithiol with
      selenium tetrachloride. Crystals of this compound are not isomorphous with the
      related benzo[2,1-c:3,4-c']bis(1,2,3-dithiazole) (BT); a structure is adopted
      that allows for more extensive intermolecular Se- - -Se contacts. Electro
      oxidation of BSe in the presence of [n-Bu4N][ClO4] affords metallic green needles
      of the charge transfer salt [BSe]3[ClO4]2, which exhibit a pressed pellet
      conductivity sigma(RT) = 10(-1) S cm(-1). The crystal structure of [BSe]3[ClO4]2
      consists of slipped pi-stacks based on the triple-decker closed shell [BSe]3(2+)
      building block. The packing is analogous to that found for the charge transfer
      salt [BT]3[FSO3]2, for which sigma(RT) = 10(-2) S cm(-1). Extended Huckel band
      structure calculations on these two (sulfur- and selenium-based) 3:2 salts reveal
      more extensive intermolecular interactions in the selenium compound. As a result,
      the latter has a more two-dimensional electronic structure. Crystal data for
      Se2S2N2C6H2, a = 4.103(2) A, b = 12.159(2) A, c = 16.171(2) A, orthorhombic,
      Pbnm, Z = 4. Crystal data for Se6S6N6C18H6Cl2O4, a =17.00(1) A, b = 18.36(1) A, c
      = 10.679(4) A, 110.27(3), monoclinic, C2/c, Z = 4.

PMID- 11511221
TI  - Synthesis and structure of [K(+)-(2,2)diaza-[18]-crown-6][K3Ge9]
      2ethylenediamine: stabilization of the two-dimensional layer
      (2)(infinity)[K3Ge9(1-)].
AB  - Large bright-red, transparent crystalline plates of [K-(2,2)diaza-[18]-crown
      6]K3Ge9-2en are obtained, in high-yield, from a reaction of (2,2)diaza-[18]-crown
      6 in toluene with a solution of K4Ge9/potassium metal (K) in ethylenediamine
      (en). The compound crystallizes in the monoclinic space group P2(1)/m (a =
      10.740(1) A, b = 15.812(1) A, c = 12.326(1) A, beta = 114.74 degrees; Z = 2). The
      crystal structure of [K-(2,2)diaza-[18]-crown-6]K3Ge9-2en features two
      dimensional [K3Ge9] layers formed by uncomplexed K(+) cations and Ge94(-) anions.
      The "not-so-bare" cluster compound features a unique Ge94(-) cluster that
      exhibits a slightly distorted C(2v) geometry that is closer to D(3h) than the
      expected C(4v). Use of noncryptand sequestering agents in the isolation of Ge
      cluster anions from en solutions opens new avenues in understanding important
      cation-anion interactions in the stability and reactivity of Zintl ions, as well
      as a viable route to isolating Zintl anions with higher charges per atom.

PMID- 11511220
TI  - Anion binding with two polyammonium macrocycles of different dimensionality.
AB  - A comparative study of the binding of nitrate and sulfate with a polyammonium
      monocycle L(1), (3,6,9,17,20,23-hexaazatricyclo[23.3.1.1(11,15)]-triaconta
      1(29),11,13,15(30),25,27-hexaene), and the corollary bicycle L(2),
      (1,4,12,15,18,26,31,39-octaazapentacyclo-[13.13.13.1(6,10).1(20,24).1(33,37)]
      tetratetraconta-6,7,9,20(43),21,23,33(42),34,36-nonaene), is reported.
      Potentiometric studies indicated negligible binding for L(1) and nitrate, but
      high affinity was observed for sulfate (log K(H5L(SO4)/H5L-SO4) = 3.53(1), log
      K(H6L(SO4)/H6L-SO4) = 4.36(1)). Stronger binding was observed for the cryptand
      L(2) with both nitrate and sulfate (log K(H6L(NO3)/H6L-NO3) = 3.11(5), log
      K(H7L(NO3)/H7L-NO3) = 3.55(5); log K(H6L(SO4)/H6L-SO4) = 4.43(1), log
      K(H7L(SO4)/H7L-SO4) = 4.97(5)). Five crystal structures are reported: the nitrate
      (1) and sulfate (2) salts of L(1), the free base (3) of L(2), and the nitrate (4)
      and tosylate (5) salts of L(2). Structural results for L(1) indicate relatively
      planar monocycles with cis and trans orientations of the phenyl groups for 2 and
      1, respectively, with the anions above and below the monocycle rings. For L(2),
      key features include an encapsulated water and intricate water network in 3, two
      encapsulated and four external nitrates and two external water molecules in 4,
      and six external tosylates with sulfonate groups pointing into the cavity and
      eight external waters in 5.

PMID- 11511222
TI  - Synthesis, structure, and electronic properties of monomeric and dimeric
      trispyrazolylborate platinum(II) hydride complexes.
AB  - Tp'PtMe(H)2 (2) [Tp' = hydridotris(3,5-dimethylpyrazolyl)borate] has been
      prepared from Tp'PtMe(CO) (1) via reaction with water in a basic acetone/water
      mixture. Protonation of 2 at one of the pyrazole nitrogen atoms induces methane
      elimination, and the resulting platinum(II) monohydride solvent intermediate (3)
      can be trapped by added ligand. Two chiral cationic platinum(II) monohydride
      complexes of the type [kappa(2)-((Hpz)BHpz2)Pt(H)(L)][BAr'4] [L = MeCN (4),
      CH2=CH2 (5); pz = 3,5-dimethylpyrazolyl, BAr'4 = tetrakis(3,5
      trifluoromethylphenyl)borate] have been isolated. If 2 is protonated in the
      absence of trapping ligand, a deep red hydride-bridged dinuclear complex,
      [kappa(2)-((Hpz)BHpz2)Pt(mu-H)]2[BAr'4]2 (6), forms. DFT calculations supplement
      intuitive expectations regarding 3-center-2-electron bridging orbital
      descriptions for the electronic structure of this complex. X-ray structure
      determinations for the monomeric acetonitrile adduct 4 and the dicationic dimer 6
      are reported.

PMID- 11511223
TI  - Hydrogen-bonding cavities about metal ions: synthesis, structure, and physical
      properties for a series of monomeric M-OH complexes derived from water.
AB  - The tripodal ligand N[CH2CH2NHC(O)NHC(CH3)3]3 ([H61]) was used to synthesize a
      series of monomeric complexes with terminal hydroxo ligands. The complexes
      [Co(II/III)H31(OH)](2-/1-), [Fe(II/III)H31(OH)](2-/1-), and [Zn(II)H31(OH)](2-)
      have been isolated and characterized. The source of the hydroxo ligand in these
      complexes is water, which was confirmed with an isotopic labeling study for
      [Co(III)H31(OH)](1-). The synthesis of [M(II)H31(OH)](2-) complexes was
      accomplished by two routes. Method A used 3 equiv of base prior to metalation and
      water binding, affording yields of < or = 40% for [Co(II)H31(OH)](2-). When 4
      equiv of base was used (method B), yields ranged from 50% to 70% for all of the
      M(II)H31(OH)](2-) complexes. This improvement is attributed to the presence of an
      intramolecular basic site within the cavity, which scavenges protons produced
      during formation of the M(II)-OH complexes. The molecular structures of
      [Zn(II)H31(OH)](2-), [Fe(II)H31(OH)](2-), [Co(II)H31(OH)](2-), and
      [Co(III)H31(OH)](1-) were examined by X-ray diffraction methods. The complexes
      have trigonal bipyramidal coordination geometry with the hydroxo oxygen trans to
      the apical nitrogen. The three M(II)-OH complexes crystallized with nearly
      identical lattice parameters, and each contains two independent anions in the
      asymmetric unit. The complexes have intramolecular H-bonds from the urea cavity
      of [H31](3-) to the coordinated hydroxo oxygen. All the complexes have long M
      O(H) bond lengths (>2.00 A) compared to those of the few previously characterized
      synthetic examples. The longer bond distances in [M(II)H31(OH)](2-) reflect the
      intramolecular H-bonds in the complexes. The five-coordinate [Zn(II)H31(OH)](2-)
      has an average Zn-O(H) distance of 2.024(2) A, which is similar to that found for
      the zinc site in carbonic anhydrase II (2.05(2) A). The enzyme active site also
      has an extensive network of intramolecular H-bonds to the hydroxo oxygen.
      [Co(II)H31(OH)](2-) and [Fe(II)H31(OH)](2-) have one-electron redox processes at 
      0.74 and -1.40 V vs SCE. Both complexes can be chemically oxidized to yield their
      corresponding M(III)-OH complexes. [Co(III)H31(OH)](1-), with an S = 1 ground
      state, is a rare example of a paramagnetic Co(III) complex.

PMID- 11511224
TI  - Synthesis and characterization of copper-, zinc-, manganese-, and cobalt
      substituted dimeric heteropolyanions, [(alpha-XW9O33)2M3(H2O)3](n-) (n = 12, X
      =As(III), Sb(III), M = Cu(2+), Zn(2+); n = 10, X = Se(IV), Te(IV), M = Cu(2+) and
      [(alpha-AsW9O33)2WO(H2O)M2(H2O)2](10-) (M = Zn(2+), Mn(2+), Co(2+).
AB  - Interaction of the lacunary [alpha-XW9O33](9-) (X = As(III), Sb(III)) with Cu(2+)
      and Zn(2+) ions in neutral, aqueous medium leads to the formation of dimeric
      polyoxoanions, [(alpha-XW9O33)2M3(H2O)3](12-) (M = Cu(2+), Zn(2+); X = As(III),
      Sb(III)), in high yield. The selenium and tellurium analogues of the copper
      containing heteropolyanions are also reported: [(alpha-XW9O33)2Cu3(H2O)3](10-) (X
      = Se(IV), Te(IV)). The polyanions consist of two [alpha-XW9O33] units joined by
      three equivalent Cu(2+) (X = As, Sb, Se, Te) or Zn(2+) (X = As, Sb) ions. All
      copper and zinc ions have one terminal water molecule resulting in square
      pyramidal coordination geometry. Therefore, the title anions have idealized D3h
      symmetry. The space between the three transition metal ions is occupied by three
      sodium ions (M = Cu(2+), Zn(2+); X = As(III), Sb(III)) or potassium ions (M =
      Cu(2+); X = Se(IV), Te(IV)) leading to a central belt of six metal atoms
      alternating in position. Reaction of [alpha-AsW9O33](9-) with Zn(2+), Co(2+), and
      Mn(2+) ions in acidic medium (pH = 4-5) results in the same structural type but
      with a lower degree of transition-metal substitution, [(alpha
      AsW9O33)2WO(H2O)M2(H2O)2](10-) (M = Zn(2+), Co(2+), Mn(2+)). All nine compounds
      are characterized by single-crystal X-ray diffraction, IR spectroscopy, and
      elemental analysis. The solution properties of [(alpha-XW9O33)2Zn3(H2O)3](12-) (X
      = As(III), Sb(III)) were also studied by 183W-NMR spectroscopy.

PMID- 11511225
TI  - Water exchange in fluoroaluminate complexes in aqueous solution: a variable
      temperature multinuclear NMR study.
AB  - An 17O, 19F, and 27Al NMR study of fluoroaluminate complexes (AlFn(H2O)6-n((3
      n)+), n = 0, 1, and 2) in aqueous solution supports the idea that for each
      substitution of a bound water molecule by a fluoride anion, the exchange rate of
      bound water with free water increases by about 2 orders of magnitude. New rate
      coefficients for exchange of inner-sphere water molecules in AlF(H2O)5(2+) are
      kex(298) = 230(+/-20) s(-1), DeltaH(dagger) = 65(+/-3) kJ mol(-1), and
      DeltaS(dagger) = 19(+/-10) J mol(-1) K(-1). The corresponding new values for the
      AlF2(H2O)4(+) complex are: kex(298) = 17 100(+/-500) s(-1), DeltaH(dagger) =
      66(+/-2) kJ mol(-1), and DeltaS(dagger) = 57(+/-8) J mol(-1) K(-1). When these
      new results are combined with those of our previous study,(4) we find no
      dependence of the solvent exchange rate, in either AlF(H2O)5(2+) or
      AlF2(H2O)4(+), on the concentration of fluoride or protons over the range of
      SigmaF = 0.06-0.50 M and [H(+)] = 0.01-0.44 M. A paramagnetic shift of 27Al
      resonances results from addition of Mn(II) to the aqueous solution as a
      relaxation agent for bulk waters. This shift allows resolution of the AlFn(H2O)6
      n((3-n)+) species in 27Al NMR spectra and comparison of the speciation determined
      via thermodynamic calculations with that determined by 27Al, 19F, and 17O NMR.

PMID- 11511226
TI  - Some chemical properties of monochlorogallane: decomposition to gallium(I)
      trichlorogallate(III), Ga(+)[GaCl3H](-), and other reactions.
AB  - Thermal decomposition of monochlorogallane, [H2GaCl]n, at ambient temperatures
      releases H2 and results in the formation of gallium(I) species, including the new
      compound Ga[GaHCl3], which has been characterized crystallographically at 100 K
      (monoclinic P2(1)/n, a = 5.730(1), b = 6.787(1), c = 14.508(1) A, beta =
      97.902(5) degrees ) and by its Raman spectrum. The gallane suffers symmetrical
      cleavage of the Ga(mu-Cl)2Ga bridge in its reaction with NMe3 but unsymmetrical
      cleavage, giving [H2Ga(NH3)2](+)Cl(-), in its reaction with NH3. Ethene inserts
      into the Ga-H bonds to form first [Et(H)GaCl]2 and then [Et2GaCl]2.

PMID- 11511227
TI  - Investigation of rational syntheses of heteroleptic porphyrinic lanthanide
      (europium, cerium) triple-decker sandwich complexes.
AB  - The use of lanthanide triple-decker sandwich molecules containing porphyrins and
      phthalocyanines in molecular information storage applications requires the
      ability to attach monomeric triple deckers or arrays of triple deckers to
      electroactive surfaces. Such applications are limited by existing methods for
      preparing triple deckers. The reaction of a lanthanide porphyrin half-sandwich
      complex ((Por)M(acac)) with a dilithium phthalocyanine (PcLi2) in refluxing 1,2,4
      trichlorobenzene (bp 214 degrees C) affords a mixture of triple deckers of
      composition (Pc)M(Pc)M(Por), (Por)M(Pc)M(Por), and (Pc)M(Por)M(Pc). We have
      investigated more directed methods for preparing triple deckers of a given type
      with distinct metals in each layer. Application of the method of Weiss, which
      employs reaction of a (Por)M(acac) species with a lanthanide double decker in
      refluxing 1,2,4-trichlorobenzene, afforded the desired triple decker in some
      cases but a mixture of triple deckers in others. The approach we developed
      employs in situ formation of the lanthanide reagent EuCl[N(SiMe3)2]2 or
      CeI[N(SiMe3)2]2, which upon reaction with a porphyrin affords the half-sandwich
      complex (Por)EuX or (Por)CeX' (X = Cl, N(SiMe3)2; X' = I, N(SiMe3)2). Subsequent
      reaction with PcLi2 gives the double decker (Por)M(Pc). The (Por(1))EuX half
      sandwich complex gave the desired triple decker upon reaction with (Pc)Eu(Pc) but
      little of the desired product upon reaction with (Por(2))Eu(Pc). The (Por(1))CeX'
      half-sandwich complex reacted with europium double deckers (e.g.,
      (tBPc)Eu(Por(2)), (tBPc)2Eu) to give the triple deckers
      (Por(1))Ce(tBPc)Eu(Por(2)) and (Por(1))Ce(tBPc)Eu(tBPc) in a rational manner (tB
      = tetra-tert-butyl). The reactions yielding the half-sandwich, double-decker, and
      triple-decker complexes were performed in refluxing bis(2-methoxyethyl) ether (bp
      162 degrees C). The porphyrins incorporated in the various triple deckers include
      meso-tetrapentylporphyrin, meso-tetra-p-tolylporphyrin, octaethylporphyrin, and
      meso-tetraarylporphyrins bearing iodo, ethynyl, or iodo and ethynyl substituents.
      The triple deckers bearing iodo and/or ethynyl substituents constitute useful
      building blocks for information storage applications.

PMID- 11511228
TI  - Synthesis of multicomponent systems composed of one phthalocyanine and four
      terpyridine ligands.
AB  - Two phthalocyanine-based multiple ligands were synthesized and characterized.
      Photochemical and electrochemical properties were measured for zinc(II)
      phthalocyanines covalently linked with four ruthenium(II) bisterpyridyl
      complexes. The absorption and electrochemical results are indicative of
      electronic interaction between two photoactive and redox-active components.
      Fluorescence spectroscopy of the five nuclear complexes provides evidence of an
      efficient photoinduced intramolecular energy transfer between the ruthenium-based
      metal-to-ligand charge-transfer (MLCT) chromophores and the zinc(II)
      phthalocyanine core. The absorption and fluorescence spectra of the
      phthalocyanine-based multiple ligands change dramatically as a result of the
      coordination of metal ions with peripheral terpyridine ligands. This change of
      fluorescence intensity upon addition of metal ions can apply to an output signal
      for metal ion sensing. The direct attachment of metal ion receptors with a zinc
      phthalocyanine core enhanced efficiency of the energy- and electron-transfer
      reaction from the core to the metal complexes.

PMID- 11511229
TI  - Synthesis and X-ray crystal structure determination of first examples of donor
      functionalized terphenyl lanthanide complexes.
AB  - The molecular structures of novel donor-functionalized terphenyl derivatives of
      trivalent ytterbium, yttrium, and samarium of composition [DanipYb(mu2-Cl)2(mu3
      Cl)Li(THF)]2 (1) and [DanipLn(mu2-Cl)2(mu2-Cl)Li(THF)2]2 (Ln = Y, 2; Ln = Sm, 3)
      are reported [Danip = 2,6-di(o-anisol)phenyl]. The complexes are obtained from
      the reaction of equimolar amounts of DanipLi and LnCl3 (Ln = Yb, Y, Sm) in
      tetrahydrofuran at room temperature in 60% yield. 1-2 toluene crystallizes in the
      monoclinic space group Ponebar. Crystal data for 1-2 toluene at 203 K: a =
      9.7281(9) A; b = 12.7989(12) A; c = 13.4870(12) A; alpha = 91.553(2) degrees;
      beta = 103.957(2) degrees; gamma = 109.916(2) degrees; V = 1521.2(2) A(3); Z' =
      1; D(calcd) = 1.615 g cm(-3); R1 = 3.43%. 2-toluene crystallizes in the
      monoclinic space group Ponebar. Crystal data for 2-toluene at 203 K: a =
      10.4152(10) A; b = 12.5783(12) A; c = 14.4640(14) A; alpha = 69.963(2) degrees;
      beta = 80.900(2) degrees; gamma = 66.603(2) degrees; V = 1633.3(3) A(3); Z' = 1;
      D(calcd) = 1.386 g cm(-3); R1 = 4.07%. 3-toluene crystallizes in the monoclinic
      space group Ponebar. Crystal data for 3-toluene at 203 K: a = 10.3457(8) A; b =
      12.5658(10) A; c = 14.4365(11) A; alpha = 70.2250(10) degrees; beta = 81.2820(10)
      degrees; gamma = 66.8330(10) degrees; V = 1623.3(2) A(3); Z' = 1; D(calcd) =
      1.521 g cm(-3); R1 = 3.40%. Complexes 1-3 represent first examples of donor
      functionalized terphenyl complexes of the elements ytterbium, yttrium, and
      samarium, respectively. The molecular structures of 1-3 feature a "constraint
      geometry" type arrangement of the Danip ligand at the lanthanide atom. The
      complexes reported are dimeric and composed of lithium chloride bridged
      DanipLnCl(2) moieties (Ln = Yb, Y, Sm), stabilized through additional
      coordination of two methoxy functions to the lanthanide atom.

PMID- 11511231
TI  - Synthesis, structure, spectroscopic properties, and magnetic properties of an
      octakis(alkylthio)-substituted lutetium(III) bisphthalocyanine.
AB  - The synthesis of a new sandwich lutetium(III) bisphthalocyanine substituted with
      hexylthio groups (1), [(C6H1)S)8-Pc]2Lu, is described. The compound is very
      soluble in most common organic solvents and has been fully characterized
      (elemental analysis, IR, 1H and 13C NMR, UV-vis spectroscopy, mass spectrometry).
      The chemically oxidized and reduced forms have been formed and characterized. The
      crystal structure of the compound (1) has been determined by X-ray diffraction on
      a single crystal. It crystallizes in the monoclinic space group C2/c with a =
      31.558(2) A, b = 32.755(2) A, c = 20.489(1) A, beta = 127.119(1) degrees, and Z =
      4. The temperature dependence of the magnetic susceptibility, measured on
      polycrystalline samples and in the range 6-300 K, is in agreement with one
      unpaired electron per molecular unit as found for the unsubstituted derivative.
      The magnetic results can be modeled assuming one-dimensional chain of spin S =
      1/2 with g = 2.04 and an antiferromagnetic coupling (J = -11.83 cm(-1), H = 
      2JSigmaSiSj).

PMID- 11511230
TI  - Synthesis of paramagnetic tetranuclear rhodium and iridium complexes with the 2,6
      pyridinedithiolate ligand. Redox-induced degradation to diamagnetic triiridium
      compounds.
AB  - The tetranuclear complexes [M4(mu-PyS2)2(diolefin)4] [PyS2 = 2,6
      pyridinedithiolate; M = Rh, diolefin = cod (1,5-cyclooctadiene) (1), tfbb
      (tetrafluorobenzo[5,6]bicyclo[2.2.2]octa-2,5,7-triene) (2); M = Ir, diolefin =
      cod (3), tfbb (4)] exhibit two one-electron oxidations at a platinum disk
      electrode in dichloromethane at potentials accessible by chemical reagents. The
      rhodium tetranuclear complexes were selectively oxidized to the monocationic
      complexes [Rh4(mu-PyS2)2(diolefin)4](+) (1(+), 2(+)) by mild one-electron
      oxidants such as [Cp2Fe](+) or [N(C6H4Br-4)3](+) and isolated as the PF6(-), BF4(
      ), and ClO4(-) salts. Silver salts behave as noninnocent one-electron oxidants
      for the reactions with the rhodium complexes 1 and 2 since they give sparingly
      soluble coordination polymers. The complex [Ir4(mu-PyS2)2(cod)4](+) (3(+)) was
      obtained as the tetrafluoroborate salt by reaction of 3 with 1 molar equiv of
      AgBF4, but the related complex 4(+) could not be isolated from the chemical
      oxidation of [Ir4(mu-PyS2)2(tfbb)4] (4) with AgBF4. Oxidation of 3 and 4 with 2
      molar equiv of common silver salts resulted in the fragmentation of the complexes
      to give the diamagnetic triiridium cations [Ir3(mu-PyS2)2(diolefin)3](+). The
      molecular structure of [Ir3(mu-PyS2)2(cod)3]BF4, determined by X-ray diffraction
      methods, showed the three metal atoms within an angular arrangement. Both 2,6
      pyridinedithiolate tridentate ligands bridge two metal-metal bonded d(7) centers
      in pseudo octahedral environments and one d(8) square-planar iridium center. An
      interpretation of the EPR spectra of the 63-electron mixed-valence paramagnetic
      tetranuclear complexes suggests that the unpaired electron is delocalized over
      two of the metal atoms in the complexes 1(+)-3(+).

PMID- 11511232
TI  - Hydrogen-bonding in ethanol adducts to bis(3-R-penta-2,4-dionato)nickel(II)
      species.
AB  - Ethanol adducts of bis(3-R-penta-2,4-dionato) nickel(II) have been prepared by
      recrystallization of the corresponding nickel bisacetylacetonate species from
      ethanol, and their crystal structures have been determined by X-ray diffraction:
      R = methyl, C16H30NiO6, a = 5.177(1), b = 9.326(1), c = 9.649(1), a = 95.39(1),
      beta = 100.04(1), gamma = 97.16(1), space group Ponebar, Z = 1; R = hex-5-enyl,
      C26H46NiO6, a = 5.176(1), b = 9.677(1), c = 14.458(1), a = 92.333(3), beta =
      93.945(4), gamma = 96.011(6), space group Ponebar, Z = 1; R = phenyl, C26H34NiO6,
      a = 27.399(1), b = 5.349(1), c = 19.827(2), beta = 117.410(7), space group C2/c,
      Z = 4. The compounds show remarkable differences in their ability to form
      hydrogen bonds in the solid phase and in solution, depending upon the nature of
      the substituent in the 3-position of the acetylacetone fragment. Analysis of the
      strength of hydrogen bonds within the limits of supermolecular approximation
      based on the results of calculations by DFT method has been carried out and were
      found to correlate with experimental observations.

PMID- 11511234
TI  - A diruthenum(III) complex possessing a diazine and two chloride bridges:
      synthesis, structure, and properties.

PMID- 11511233
TI  - Tridentate coordination of monosubstituted derivatives of the tris(2
      pyridylmethyl)amine ligand to FeCl3: structures and spectroscopic properties of
      ((2-bromopyridyl)methyl)bis-(2-pyridylmethyl)amine Fe(III)Cl3 and (((2-p
      methoxyphenyl)pyridyl)methyl)bis(2-pyridyl-methyl)]amine Fe(III)Cl3 and
      comparison with the bis(2-pyridylmethyl)]amine Fe(III)Cl3 complex.

PMID- 11511235
TI  - Biosynthesis of acaterin: coupling of C(5) unit with octanoate.
AB  - Acaterin (1), produced by Pseudomonas sp. A 92, is a secondary metabolite having
      a 2-penten-4-olide structure. Feeding experiments with (2)H- and (13)C-labeled
      decanoic acid, their 3-oxygenated congeners, and octanoic acid have suggested
      that 1 is biosynthesized via coupling of a C(5) unit with octanoate, rather than
      via introduction of a C(3) unit at the alpha position of a decanoate derivative.
      Further feeding study of [2,3-(13)C(2)]decanoic acid concluded that the former
      route is operating in the biosynthesis of 1.

PMID- 11511237
TI  - Synthesis, characterization, and optical response of dipolar and non-dipolar
      poly(phenylenevinylene) dendrimers.
AB  - New dipolar and non-dipolar poly(phenylenevinylene) dendrimers bearing electron
      donating and electron-withdrawing groups have been efficiently synthesized using
      Heck and Horner-Wadsworth-Emmons reactions. The photoluminescence of these
      systems may be tuned in the blue zone by choosing the appropriate peripheral
      groups. Despite the meta-substitution pattern, large Stokes shifts can be
      observed when pi-donor and pi-acceptor groups are connected by a m
      phenylenevinylene system.

PMID- 11511236
TI  - Targeted drug delivery to chemoresistant cells: folic acid derivatization of
      FdUMP[10] enhances cytotoxicity toward 5-FU-resistant human colorectal tumor
      cells.
AB  - Current chemotherapy protocols that include fluoropyrimidines, such as 5
      fluorouracil (5-FU), are limited by the development of chemoresistance during the
      course of treatment. Our laboratory has developed a novel class of
      fluoropyrimidines, FdUMP[N], that are oligodeoxynucleotides (ODNs) composed of
      some number, N, of 5-fluoro-2'-deoxyuridine-5'-O-monphosphate (FdUMP)
      nucleotides. Novel synthetic procedures are described that permit conjugation of
      folic acid to the 5'-OH of FdUMP[10] via a phosphodiester linkage using automated
      synthesis. The synthetic methods developed are generally applicable for ODN
      conjugation with folic acid. The folic acid conjugate FA-FdUMP[10] showed
      improved cytotoxicity toward human colorectal tumor cells (H630), and 5-FU
      resistant colorectal tumor cells (H630-10). Enhanced cytotoxicity was observed
      for FA-FdUMP[10] relative to nonconjugated FdUMP[10] for cells grown under folate
      restricted conditions, consistent with cellular uptake being, in part, receptor
      mediated. Folate receptor alpha (FRalpha) mRNA was shown by RT-PCR to be
      overexpressed 26.3-fold in 5-FU-resistant H630-10 cells relative to H630 cells.
      Thus, FA-FdUMP[N] may prove useful for the treatment of 5-FU-resistant
      malignancies.

PMID- 11511238
TI  - Mechanism of the ring-chain rearrangement in phosphiranes: hydrogen versus
      halogen migration.
AB  - Ab initio quantum chemical calculations including HF, MP2, CCSD(T),
      CASSCF(10,10)/CASPT2, and B3LYP methods with the 6-31G(d,p) basis set were used
      to probe the mechanism of the ring-chain rearrangement of halogeno-phosphiranes.
      It is confirmed that the lowest energy interconversion between C-halogenated-(X)
      phosphiranes and vinylphosphines, with X = H, F, Cl, and Br, is a one-step
      process in which the C-P bond cleavage and X-sigmatropic migration from C to P
      occur in a concerted manner in a single transition structure. The migration of a
      hydrogen from CH(H) is slightly favored over that of CX(H), and thus, the
      cleavage of the C(X)-P bond is preferred. The energy barrier for the whole
      process involving hydrogen migration in the parent phosphirane is calculated to
      be about 45 +/- 5 kcal/mol. The migratory aptitude of the atoms X in the
      uncomplexed species is found as follows: H > Br > Cl > F, either in the gaseous
      phase or in aqueous and DMSO solutions. The solvation enthalpies that were
      estimated using a polarizable continuum model (PCM) are rather small and do not
      modify the relative ordering of the energy barriers. Such a trend is at variance
      with recent experimental findings on metal-phosphinidene complexes in which only
      halogen migration was observed. This might arise from a peculiar effect of the
      metal fragments W(CO)(5) used in the experimental studies to stabilize the
      phosphorus species that induce a quite different mechanism. Calculations of the
      (31)P chemical shifts using the GIAO/B3LYP/6-311+G(d,p) method show a remarkable
      correlation between the delta(31)P(X) chemical shifts of X-phosphiranes and those
      of X-phosphines (XCH(2)PH(2)), suggesting that the large beta substituent effect
      is not inherent to the small rings.

PMID- 11511239
TI  - Electronic and steric effects in thermal denitrosation of N-nitrosoamides.
AB  - N-Alkyl-N-nitrosoamides undergo competitive reactions whose rates are dependent
      upon the interplay of a number of factors. There already exists a significant
      body of work delineating the effects of pH on the partitioning of the
      nitrosoamides along their deaminative (-N(2)) and denitrosative (-"NO(+)")
      pathways. In this paper, the issue of pH dependence is discussed with particular
      attention to nitrosoamide decompositions in nonaqueous media. The role of the
      acidity of the medium in the partitioning of the nitrosoamide between deamination
      and denitrosation and in the choice of deaminative pathways is revisited. In
      nonaqueous media under near-neutral conditions, the partitioning's pH dependence
      is evidently accompanied by a sensitivity to structural features in the
      nitrosoamide. Thus, diminution of steric crowding around the N-nitroso moiety as
      well as the presence of strongly electron-withdrawing acyl units (i.e., those
      derived from strong acids, e.g., tosyl and trifyl) increase the relative yield of
      amides by encouraging the denitrosative pathway. A mechanism for thermal
      denitrosation of nitrosoamides under near-neutral conditions is proposed in which
      rapid protonation at the acyl O rather than slow protonation at the amidic N is
      the first step in the reaction profile. A rate-limiting, bimolecular reaction
      between the O-conjugate acid and adventitious nucleophiles at the nitrosyl group
      then occurs followed by rapid tautomerization to amide.

PMID- 11511240
TI  - Thermal and photochemical epimerization/equilibration of carbohydrate
      cobaloximes.
AB  - Epimeric carbohydrate alkyl cobaloximes 4:5, 9:10, and 12:13 can be equilibrated
      thermally or photochemically. In each case, one isomer is strongly favored: exo-3
      deoxy-3-pyridyldimethylglyoximatocobalt-1,2:5,6-di-O-isopropylidene-alpha-D
      glucofuranose 4 for the 4:5 epimer pair, exo-3-deoxy-3
      pyridyldimethylglyoximatocobalt-5-O-carboxymethyl-1,2-O-isopropylidene-alpha-D
      xylofuranose 9 for the 9:10 epimer pair, and equatorial 1-deoxy-1
      pyridyldimethylglyoximatocobalt-2,3,4,6-tetra-O-benzyl-beta-D-glucopyranose 12
      for the 12:13 epimer pair. These data indicate that there is a strong facial
      preference for the coupling of py(dmgH)(2)Co(*) radicals with alkyl R(*) free
      radicals, with the preferred kinetic path leading to the more stable product.

PMID- 11511241
TI  - Intracellular oxidation of dipeptides. Base-promoted elimination from N
      halodipeptides to 2-[N-alkyl-N-(2-N-alkylimino-2-alkyl-ethanoyl)amino]-2,2
      dialkylethanoic acids.
AB  - One of the possible ways of intracellular oxidation of peptides is via the
      formation of the corresponding (N-X)-dipeptides, that then undergo base-promoted
      elimination to yield intermediate 2-[N-alkyl-N-(2-N-alkylimino-2
      alkylethanoyl)amino]-2,2-dialkylethanoic acids, which subsequently hydrolyze.
      Such an elimination process is general-base catalyzed, with Bronsted beta values
      ranging from 0.26 to 0.31, which suggests an essentially constant degree of
      proton transfer at the TS. For (N-X)-dipeptides, the ratio k(N-Br)/k(N-Cl) ranges
      from 2.5 to 15, suggesting a structural dependence of the degree of N-X bond
      breaking at the TS. The values of beta and k(N-Br)/k(N-Cl) support a concerted
      asynchronous A(xh)D(H)D(N) mechanism, its TS changing from reactant-like to
      slightly nitrenium-like depending on the structure of the starting dipeptide. As
      a consequence of the antiperiplanarity requirements of the reaction, the steric
      interaction between the leaving group and the substituent on the C bearing the H
      to be eliminated controls the reaction rate. Such steric interaction is rather
      important, as indicated by the steric crossed-interaction coefficient (p(ssy') =
      0.33). Semiempirical calculations show that bulky substituents in the vicinity of
      the reaction center imply additional energy requirements for the system to
      achieve the antiperiplanarity needed at the TS for the reaction to proceed. From
      the observations reported it follows that (N-X)-dipeptides lose their oxidizing
      power more readily than analogous (N-X)-amino acids or (N-X)-amines, opening a
      possible pathway to lessen intracellular halogen-based oxidative stress.

PMID- 11511242
TI  - Supramolecular assistance to regioselectivity in the reactions of
      chlorocyclophosphazenes with sodium oxyanions: macrocyclic effect and anion
      dependence.
AB  - Comparative studies of the naphtholysis of crown-bearing
      tetrachlorocyclotriphosphazene 2 and its acyclic analogue, nongem
      diethoxytetrachlorocyclotriphosphazene 5 (which was synthesized and isolated in
      the pure cis form for the purpose of this study), reveal a significant
      macrocyclic effect of the substituent on both the kinetics and regiochemistry of
      chlorine substitution in the N(3)P(3) ring. Whereas substitution of 5 with sodium
      naphthoxide provided moderate yields of the respective sterically and
      electronically favored nongem-naphthoxydiethoxy derivative as the major product,
      isolated as the mixture of cis and trans isomers 8 + 9, the corresponding
      reaction of crown substrate 2 resulted in highly regioselective formation of the
      gem-to-macrocycle substituted mononaphthoxy PNP-crown derivative 11a. The
      importance of the PNP-crown related effects for the regio- and stereocontrol of
      the substitution of chlorine atoms in the N(3)P(3) ring is discussed in terms of
      supramolecular sodium cation-assisted interactions between the ring oxy
      substituent(s) and incoming oxyanions. To approach the problem of the anion
      dependence of the regioselectivity, a comparison has been drawn between the
      reactions of the PNP-crown substrate 2 with sodium arylates derived from beta
      naphthol (10a) and phenol (10b), carried out with equimolar or 100% excess sodium
      oxyanion with respect to 2, and the corresponding reactions of 2 with sodium
      monoenolates derived from the beta-dicarbonyl compounds: acetylacetone (10c) and
      ethyl acetylacetate (10d). The effectiveness of supramolecularly assisted
      transition state stabilization is found to be dependent not only on the
      dimensional complementarity between the cation and the macrocycle but also on the
      properties of the four interacting ionic centers according to the HSAB principle
      and on the nature of the electronic interaction of the PNP-crown substituent with
      the N(3)P(3) ring, the latter determining the extent of regiocontrol to either
      one or two macrocyclic chloride functions. The increase of the extent of
      regioselectivity of gem-substitution at the PNP-macrocycle when passing from
      arylate to beta-dicarbonyl enolate oxy anions is related to the observed trends
      in the (31)P NMR chemical shifts and refers to the electronic structure of the
      oxy substituent.

PMID- 11511243
TI  - Generation of azines by the reaction of a nucleophilic carbene with diazoalkanes:
      a synthetic and crystallographic study.
AB  - Reactions of the nucleophilic carbene 1,3-dimesityl-imidazol-2-ylidene (1) with
      diazofluorene, diphenyldiazomethane, and azidotrimethylsilane were examined.
      Specifically, carbene 1 reacts with diazofluorene and diphenyldiazomethane to
      give addition products (azines: 3 and 4, respectively). Compounds 3 and 4 were
      further characterized in the solid-state by single-crystal X-ray crystallographic
      studies. [3 (a = 9.7936(6) A, b = 10.0529(7) A, c = 16.251(1) A, alpha =
      75.765(1) degrees, beta = 79.711(1) degrees, gamma = 64.321(1) degrees, Z = 2,
      space group P1); 4 (a = 11.681(3) A, b = 11.861(4) A, c = 21.186(3) A, alpha = 90
      degrees, beta = 97.05(2) degrees, gamma = 90 degrees, Z = 4, space group
      P2(1)/n)]. The structural parameters of 3 and 4 are discussed with reference to
      previously characterized symmetrical and unsymmetrical azines. Structural data
      suggest that charge separation is possible in 3.

PMID- 11511244
TI  - Highly diastereoselective synthesis of vinylcyclopropane derivatives with (-)-8
      phenylmenthol as chiral auxiliary.
AB  - The silylated telluronium allylide 4, generated in situ from the corresponding
      telluronium salt in the presence of LiTMP, reacted with (-)-8-phenylmenthyl
      alpha,beta-unsaturated esters to afford trans-2-silylvinyl-trans-3-substituted
      cyclopropyl esters with high diastereoselectivity in high yields. The absolute
      configuration was determined by chemical transformation. A mechanistic rationale
      is proposed.

PMID- 11511245
TI  - Addition of lithiated 9-deazapurine derivatives to a carbohydrate cyclic imine:
      convergent synthesis of the aza-C-nucleoside immucillins.
AB  - Means have been developed for the synthesis and addition of 9-deaza-9
      lithiopurine derivatives to the carbohydrate-derived cyclic imine 6 in facile
      convergent syntheses of biologically active aza-C-nucleosides.

PMID- 11511246
TI  - Intramolecular Friedel-Crafts-type reactions involving N-acyliminium ions derived
      from glycine templates.
AB  - Enantiomerically pure 4-substituted 2-aralkyl-2,4-dihydro-1H-pyrazino[2,1
      b]quinazoline-3,6-diones (1b-m) in which the alkyl chain is (CH(2))(n), n = 1-3,
      behave as glycine templates giving by treatment with
      [hydroxy(tosyloxy)iodo]benzene in ethyl acetate cis-1-tosyloxy derivatives. When
      these compounds contain electron-rich aryl substituents with n = 2, they
      spontaneously cyclize through intramolecular Friedel-Crafts-type
      diastereoselective reactions to give penta- or hexacyclic compounds. Otherwise,
      they give by solvolysis cis-1-alkoxy derivatives, which in a second step, may be
      cyclized in acid if n = 2, 3. All these reactions must occur through N
      acyliminium species in S(N)1-like mechanisms. 1-Alkoxy-2-arylmethyl derivatives
      are reluctant to cyclize, giving trans-1-hydroxy compounds as the only isolated
      reaction products.

PMID- 11511247
TI  - Molecular engineering. 8. Kinetic and conformational studies of resorcin [4]arene
      based C4 tetraoxatetrathiahemicarceplexes: carceroisomerism and twistomerism.
AB  - New C(4v) tetraoxatetrathiahemicarcerands and their six hemicarceplexes
      containing DMF, DMA, DMSO, or NMP were synthesized and characterized. Their
      conformations, kinetic properties, carceroisomerism, and twistomerism were
      studied by VT, 2D COSY, NOESY, and ROESY (1)H NMR experiments. The decomplexation
      rates of DMF or DMA were very slow with high activation energy barriers (73 and
      104 kJ mol(-1), respectively) and the complexed guests feel more constriction
      than their free liquid state. The largest isomerization energy barrier of
      carceroisomers was 15.4 kcal mol(-1), and the isomerization energy barriers of
      twistomers are significantly larger than those of carceroisomers.

PMID- 11511248
TI  - Pentagonal dodecahedranes: polyfunctionalization and MS fragmentation.
AB  - With the use of four- to eight-fold functionalized dodecahedranes (1-3),
      opportunities to arrive at highly strained dodecahedranes with two to four pairs
      of vicinal, eclipsed bromine substituents through front-side substitution and
      addition reactions have been explored. In standard processes, the interception of
      beta-OCH(3) radical/cationic intermediates was not problematic (9-12, 37, 50).
      The interception of beta-CO(2)R radicals was possible for Cl(*) (18) but not for
      Br(*) (17). The interception of beta-chloro radicals was possible for Cl(*) (27)
      but not for Br(*) (26), and the interception of beta-Br cations ("bromonium
      ions") with Br(-) was modest (45) to highly inefficient (24, 26). Two X-ray
      structural analyses (dimethoxy dibromide 9 and tetramethoxy tetrabromide 53)
      indicated the structural consequences of the molecular strain introduced by the
      two (four) vicinal CH(3)O/Br pairs. A systematic analysis of the MS spectra
      confirms that, in virtually all cases studied, the elimination of the
      substituents occurs without significant carbon-cage disruption, leading
      ultimately to multiply unsaturated dodecahedral ions for
      dodecahedrahexa(C(20)H(8))enes, -hepta(C(20)H(6))enes, and -octa(C(20)H(4))enes.

PMID- 11511249
TI  - Nitroxyl radical reactions with 4-pentenyl- and cyclopropylketenes: new routes to
      5-hexenyl- and cyclopropylmethyl radicals.
AB  - 4-Pentenylketenes 4a and 9 and cyclopropylketenes 3a, 13, 14 (RCH=C=O) are
      generated by photochemical Wolff rearrangements and observed by IR as relatively
      long-lived species at room temperature in hydrocarbon solvents. The reactions of
      these ketenes with the nitroxyl radicals tetramethylpiperidinyloxyl (TEMPO, TO*)
      and tetramethylisoindoline-2-oxyl (TMIO, IO*) form carboxy substituted 5-hexenyl
      and cyclopropylmethyl radicals which are either trapped by a second nitroxyl
      radical or undergo rearrangements followed by trapping. The rate constant of the
      reaction of 4a with TEMPO was similar to that of n-BuCH=C=O (1b), while 3a was
      4.3 times more reactive, indicating cyclopropyl stabilization of the incipient
      radical.

PMID- 11511250
TI  - Synthesis of thiadiazole, dithietane, and imine derivatives of the
      [1,2]dithiolo[1,4]thiazine ring system.
AB  - We report the synthesis of some new polysulfur-nitrogen heterocyclics by
      cycloaddition reactions to the thioketo group of readily available tricyclic 1,2
      dithiole-3-thiones. Thus treatment of bis[1,2]dithiolo[1,4]thiazine ketothione 1
      with diaryl nitrile imines generated from hydrazonoyl chlorides 2a-g gave
      [1,3,4]thiadiazolylidenyl[1,2]dithiolo[1,4]thiazines 4a-g in high yield.
      Compounds 4a-f, bearing the same substituents in both aryl groups, were stable
      but the analogous 4g,h with a p-nitrophenyl group on carbon gave the
      bis[1,2]dithiolo[1,4]thiazine dione 9, probably by cycloreversion and hydrolysis
      during chromatography. Treatment of 1, the bis[1,2]dithiolopyrrole ketothione 13,
      and dithione 12 with ethoxycarbonyl azide 11 gave imines 12 and 15 and bisimine
      16, respectively, by an alternative fragmentation of the initial cycloadduct in
      which the 1,2-dithiole ring is retained. Reaction of 1 with TosMIC gave the imino
      1,3-dithietane 17.

PMID- 11511252
TI  - Synthesis of bicyclic pyrimidine derivatives as ATP analogues.
AB  - A highly efficient and general solid-phase synthesis of bicyclic pyrimidine
      derivatives that target purine dependent proteins is reported. The synthesis of
      the key intermediate, 4,6-disubstituted-5-amino-pyrimidine, involved reduction of
      the corresponding nitro derivatives using 1,1'-dioctyl-viologen in a triphasic
      milieu. The mild reduction conditions enable the use of any acid labile solid
      support as well as a wide range of combinatorial substituents, thus enabling the
      synthesis of large libraries of highly diverse bicyclic pyrimidines. Alternative
      reduction conditions with tin(II) chloride and structure-reactivity studies are
      discussed as well.

PMID- 11511251
TI  - Synthesis of novel retinoid X receptor-selective retinoids.
AB  - Retinoids 1-5 have been identified as potent RXR agonists for evaluation in the
      treatment of non-insulin-dependent (type II) diabetes mellitus (NIDDM). Highly
      convergent syntheses of 1-5 have been developed. The core tetrahydronaphthalene
      7, employed in the synthesis of 1 and 2, was prepared in 98% yield using an
      AlCl(3)-catalyzed (0.03 equiv) Friedel-Crafts alkylation of toluene with 2,5
      dichloro-2,5-dimethylhexane 6. A nitromethane-mediated Fridel-Crafts acylation of
      7 with chloromethylnicotinate 9 was developed to prepare ketone 10 in 68% yield.
      Chelate-controlled addition of MeMgCl to 10 followed by dehydration afforded
      olefin 11 in 65% yield. Cyclopropanation of 11 with trimethylsulfoxonium ylide,
      followed by saponification, completed a five-step synthesis of 1 in 33% yield.
      FeCl(3)-catalyzed (0.05 equiv) Friedel-Crafts acylation of 7 with
      chloromethylterephthalate 14 afforded ketone 15 in 81% yield. Saponification of
      15 and reaction with 50% aqueous NH(2)OH in AcOH afforded a 9:1 mixture of cis
      and trans oximes, from which the desired cis-oxime 2 was isolated in 43% yield.
      The core bromo-dihydronaphthalene 29 required for the synthesis of 3-5 was
      prepared by a Shapiro reaction. Transmetalation of 29 and reaction with Weinreb
      amides 30b or 36 afforded ketones 32 and 37, which were converted into 3-5 using
      chemistry comparable to the tetrahydronaphthylene series. Suzuki coupling of
      boronic acids 41 and 42 with vinyl triflate 43 provided an alternative approach
      to the synthesis of this class of compounds.

PMID- 11511253
TI  - Highly stereoselective synthesis of anti-N-protected-alpha-amino epoxides.
AB  - A simple and efficient method for the synthesis of anti-N-protected amino
      epoxides from carbamate-protected amino acids is described. The two key steps are
      the monobromination of a beta-ketoester and chelation-controlled reduction of a
      bromomethyl ketone intermediate. Good overall yields, high diastereoselectivity,
      and excellent functional group compatibility are characteristic.

PMID- 11511254
TI  - Enantioselective epoxidation with chiral MN(III)(salen) catalysts: kinetic
      resolution of aryl-substituted allylic alcohols.
AB  - A set of aryl-substituted allylic alcohols rac-2 has been epoxidized by chiral
      Mn(salen*) complexes 1 as the catalyst and iodosyl benzene (PhIO) as the oxygen
      source. Whereas one enantiomer of the allylic alcohol 2 is preferentially
      epoxidized to give the threo- or cis-epoxy alcohol 3 (up to 80% ee) as the main
      product (dr up to >95:5), the other enantiomer of 2 is enriched (up to 53% ee).
      In the case of 1,1-dimethyl-1,2-dihydronaphthalen-2-ol (2c), the CH oxidation to
      the enone 4c proceeds enantioselectively and competes with the epoxidation. The
      absolute configurations of the allylic alcohols 2 and their epoxides 3 have been
      determined by chemical correlation or CD spectroscopy. The observed diastereo-
      and enantioselectivities in the epoxidation reactions are rationalized in terms
      of a beneficial interplay between the hydroxy-directing effect and the attack
      along the Katsuki trajectory.

PMID- 11511255
TI  - Aziridine ring-opening reactions with chiral enolates. Stereocontrolled synthesis
      of 5-substituted-3-methyl-pyrrolidin-2-ones.
AB  - A procedure for performing stereocontrolled aziridine ring-opening reactions with
      chiral enolates derived from (S,S)-(+)-pseudoephedrine amides has been developed
      leading to gamma-aminoamides in good yields. The diastereoselectivity of the
      reaction becomes controlled by the presence of the chiral auxiliary on the
      enolate, although the stereogenic center contained in the structure of the
      aziridine has a striking influence on the stereochemical course of the reaction
      which results in the presence of the corresponding matched and mismatched
      combinations. Besides, the sense of the asymmetric induction of the chiral
      auxiliary has resulted to be the opposite to the one found with other type of
      electrophiles, although it is in good agreement with the trend observed in the
      reaction of the same kind of enolates with epoxides. Finally, the obtained gamma
      aminoamide adducts were converted into enantiopure gamma-amino acids, gamma
      aminoesters, and pyrrolidin-2-ones using easy to perform and high yielding
      reactions.

PMID- 11511256
TI  - Quantum mechanical study of the ring-closing reaction of the hexatriene radical
      cation.
AB  - The ring-closing reaction of hexatriene radical cation 1(*)(+) to 1,3
      cyclohexadiene radical cation 2(*)(+) was studied computationally at the B3LYP/6
      31G* and QCISD(T)/6-311G*//QCISD/6-31G* levels of theory. Both, concerted and
      stepwise mechanisms were initially considered for this reaction. Upon evaluation
      at the B3LYP level of theory, three of the possible pathways-a concerted C(2)
      symmetric via transition structure 3(*)(+) and stepwise C(1)-symmetric pathways
      involving three-membered ring intermediate 5(*)(+) and four-membered ring
      intermediate 6(*)(+)-were rejected due to high-energy stationary points along the
      reaction pathway. The two remaining pathways were found to be of competing
      energy. The first proceeds through the asymmetric, concerted transition structure
      4(*)(+) with an activation barrier E(a) = 16.2 kcal/mol and an overall
      exothermicity of -23.8 kcal/mol. The second pathway, beginning from the
      cis,cis,trans rotamer of 1(*)(+), proceeds by a stepwise pathway to the
      cyclohexadiene product with an overall exothermicity of -18.6 kcal/mol. The
      activation energy for the rate-determining step in this process, the formation of
      the intermediate bicyclo[3.1.0]hex-2-ene via transition structure 9(*)(+), was
      found to be 20.4 kcal/mol. More rigorous calculations of a smaller subsection of
      the potential energy hypersurface at the QCISD(T)//QCISD level confirmed these
      findings and emphasized the importance of conformational control of the reactant.

PMID- 11511257
TI  - Optimization of a synthetic arginine receptor. Systematic tuning of noncovalent
      interactions.
AB  - The simple arginine binder 1 could be optimized by strengthening pi-cation as
      well as electrostatic interactions. Electron-donating or -withdrawing
      substituents in the 5-position provide experimental evidence for pi-cation
      interactions, because binding energies increase by up to 0.6 kcal/mol due to a
      single benzene-guanidinium interaction. Even more effective is the introduction
      of a third phosphonate functionality at the correct distance, so that the
      guanidinium cation is recognized by optimal electrostatic and hydrogen bond
      interactions. Monte Carlo simulations and NOESY experiments confirm the expected
      complex geometries. The optimized host molecule 8 binds arginine half an order of
      magnitude more efficiently than the parent molecule.

PMID- 11511258
TI  - Assignment of the liposidomycin diazepanone stereochemistry.
AB  - The liposidomycins comprise a family of complex nucleoside antibiotics that
      inhibit bacterial peptidoglycan synthesis. Their structures (1, 2) feature
      nucleoside, ribofuranoside, diazepanone, and lipid regions. Several stereogenic
      centers remain unassigned, including three within the diazepanone region: C-6', C
      2'", and C-3'". An intramolecular reductive amination reaction has been used to
      prepare model diazepanones. Analysis of 40 and two of its diastereomers by NMR
      spectroscopy, X-ray crystallography, and molecular modeling indicates a close
      relative configurational and conformational match between 40 and the
      liposidomycin diazepanone degradation product 43 and allows the assignment of
      stereochemistry of the natural products as either [C-6'(R), C-2'"(R), C-3'"(R)]
      or [C-6'(S), C-2'"(S), C-3'"(S)].

PMID- 11511259
TI  - Reinvestigation of the reactions of camphorketene: structural evidence for
      pseudopericyclic pathways.
AB  - The stereochemistry of the dimers (3 and 4) of camphorketene (2) have been
      determined. The crystal structures of 3, 20 and of related compounds show ground
      state distortions that are interpreted as prefiguring planar, pseudopericyclic
      transition states for retro-cycloadditions to form alpha-oxoketenes. The B3LYP/6
      31G* optimized geometry for the transition structure (10) for the dimerization of
      s-Z-formylketene (8) is consistent with this mechanism. Trapping of 2 with
      alcohols shows selectivity comparable to other alpha-oxoketenes. The lack of
      reaction of 2 with benzaldehyde and the lack of enol tautomers in camphoric acid
      derivatives is attributed to angle strain in the bicyclic camphor moiety.

PMID- 11511260
TI  - Molecular structure and conformation of cyclopropylbenzene as determined by ab
      initio molecular orbital calculations, pulsed-jet fourier transform microwave
      spectroscopic, and gas-phase electron diffraction investigations.
AB  - Ab initio computational, microwave spectroscopic, and electron diffraction
      techniques have been used to study the gas-phase structure of cyclopropylbenzene.
      Theoretical calculations at the HF, B3LYP, and MP2 levels for basis sets 6-31G(d)
      and 6-311G(d) have been carried out. Both MP2 and B3LYP calculations showed the
      bisected form to be lower in energy (245/157 and 660/985 cal mol(-1),
      respectively, for basis sets 6-311G(d)/6-31G(d)). Rotational constants for the
      bisected form of the parent and eight singly substituted (13)C isotopic species
      were obtained. The selection rules of the observed rotational transitions and the
      facts that eight (rather than six) singly substituted (13)C isotopers are
      observed and assigned and that seven of the compound's nine carbon atoms lie in
      the molecule's symmetry plane required the molecule to exist in the bisected
      conformation. No transition from the perpendicular form was observed in the
      pulsed-jet microwave experiment. Gas-phase electron diffraction data were
      collected at a nozzle-tip temperature of 265 K. Least squares analyses were
      carried out using ED data alone and with the inclusion of microwave rotational
      constants. The principal structural results (r(g) and angle(alpha)) obtained from
      the combined ED/MW least-squares analysis are r(C-H)(av) = 1.093(6) A, r(C(7)
      C(8))(v) = 1.514(20) A, r(C(8)-C(9))(d) = 1.507(26) A, r(C(7)-C(1)) = 1.520(25)
      A, r(C-C)(Ph) = 1.395(1) A, angleC(1)C(7)C(8) = 119.6(17) degrees,
      angleC(2)C(1)C(7) = 122.5(25) degrees, angleC(1)C(2)C(3) = 120.9(35) degrees,
      angleHC(8)C(9) = 116.7(20) degrees, angleHCC(Ph) = 120.0 degrees (assumed).

PMID- 11511261
TI  - Characterization of binary solvent mixtures of DMSO with water and other
      cosolvents.
AB  - Binary mixtures of DMSO with nine different cosolvents were characterized in
      light of the pure solvent scales, using suitable probe/homomorph couples. Various
      physical (vapor pressure, surface tension, viscosity, and enthalpy of mixing) and
      spectroscopic (IR and NMR) properties of the DMSO/water mixtures are described in
      terms of their polarity, acidity, and basicity, and the descriptions are examined
      with a view to establishing their potential physical significance.

PMID- 11511262
TI  - Conformational studies by dynamic NMR. 83. Correlated enantiomerization pathways
      for the stereolabile propeller antipodes of dimesityl substituted ethanol and
      ethers.
AB  - Below -100 degrees C, the NMR spectra of dimesityl derivatives of ethanol and of
      various ethers reveal how these molecules exist as M and P propeller-like
      stereolabile enantiomers, owing to the restricted rotation about the Ar-C bond.
      Single-crystal X-ray diffraction of one such derivative confirmed the existence
      of a two-blade propeller structure. Computer analysis of the NMR line shape
      allowed the barriers for the enantiomerization process to be determined.
      Theoretical modeling (Molecular Mechanics) of the interconversion circuit
      produced good agreement between the computed and experimental barrier for a
      correlated dynamic process where a disrotatory one-ring flip pathway reverses the
      helicity of the conformational enantiomers. Introduction of a configurationally
      stable chiral center allowed two distinct NMR spectra to be detected at
      appropriate low temperature for two stereolabile diastereoisomers.

PMID- 11511263
TI  - Synthesis of a new insoluble polymer-supported chiral alcohol auxiliary and its
      first application to nucleophilic addition to ketenes.
AB  - The preparation of a new optically active alcohol with a carboxylic function that
      allowed its attachment to an amine-functionalized insoluble polymer is described.
      Its first use as a polymer supported chiral auxiliary is demonstrated by
      asymmetric transformation of two racemic aryl propionic acids via ketene
      formation (95-96% ee).

PMID- 11511264
TI  - On the magnitude and specificity of medium effects in enzyme-like catalysts for
      proton transfer.
AB  - Medium effects are normally studied by comparing the rates of reactions in
      different solvents. However, medium effects at the active site of enzymes differ
      dramatically from bulk solvents, both in their diversity (the presence of more
      than one type of "solvent") and in their spatial arrangement. We describe medium
      effects in a simple catalytic system, obtained by systematic alkylation of a
      polymeric scaffold bearing amine groups to give synzymes that catalyze the Kemp
      elimination of benzisoxazoles with remarkable efficiency. Our analysis indicates
      that catalysis by these synzymes is driven primarily by specific, localized
      enzyme-like medium effects, and these effects seem to differ dramatically from
      the nonspecific medium effects (i.e., desolvation activation) exhibited by
      solvents. Ligand-binding studies indicate that the synzyme active sites provide
      localized microenvironments affording a combination of hydrophobic and apolar
      regions on one hand and dipolar, protic, and positively charged on the other.
      Such localized microenvironments are not available in bulk solvents. A Bronsted
      (leaving group) analysis indicates that, in comparison to solvent catalysis, the
      efficiency of synzyme catalysis shows little sensitivity to leaving group pK(a).
      We show that enzyme-like medium effects alone, in the absence of efficient
      positioning of the catalytic amine base relative to the substrate, can give rise
      to rate accelerations as high as 10(5), for both activated and nonactivated
      substrates. Supported by the accidental identification of active sites on the
      surfaces of noncatalytic proteins and the promiscuous activities found in many
      enzymes, our findings suggest that the interfaces of protein surfaces and their
      hydrophobic cores provide a microenvironment that is intrinsically active and may
      serve as a basis for further evolutionary improvements to give proficient and
      selective enzymes.

PMID- 11511265
TI  - First total synthesis of (-)-ichthyothereol and its acetate.
AB  - The first and stereoselective total syntheses of (-)-ichthyothereol (1) and its
      acetate ((+)-2) were achieved by incorporation of the two chiral centers of
      diethyl L-tartrate. The starting diethyl L-tartrate was converted into trans-2
      ethynyl-3-hydroxytetrahydropyran 14 in a stereoselective manner via the endo mode
      cyclization of the epoxy-alkyne derivative 12. The alcohol 12 was then
      transformed into (E)-iodoolefin derivative 15, which was exposed to a coupling
      reaction with 1-tributylstannyl-1,3,5-heptyne (19), derived from the
      corresponding 1-trimethylsilyl-1,3,5-heptyne (18), under Stille conditions to
      produce the all-carbon framework of the target natural products. Chemical
      modification of the coupled product 20 under conventional conditions completed
      the first total synthesis of (-)-ichthyothereol (1) and its acetate ((+)-2).

PMID- 11511266
TI  - Scope and limitation of organocuprates, and copper or nickel catalyst-modified
      Grignard reagents for installation of an alkyl group onto cis-4-cyclopentene-1,3
      diol monoacetate.
AB  - Alkylation of the title compound 1 was investigated with two types of reagents.
      One is a copper reagent derived from R(T)MgX (X = Cl, Br) and CuX (X = CN, I) and
      the other is R(T)MgX in the presence of a copper or a nickel catalyst. First,
      butylation was studied with BuCu(CN)(MgX), Bu(2)Cu(CN)(MgX)(2), BuMgX/CuCN (10
      mol %), BuCu (derived from BuMgCl and CuI), and BuMgCl/CuI (10 mol %) in THF or
      Et(2)O. We found that trans 1,4-isomer 2a and/or trans 1,2-isomer 3a were
      produced exclusively with these reagents and that the stoichiometry of BuMgX/CuX
      and the choice of solvent were critical to attain high regioselectivity and
      efficient yield. Reaction with Bu(2)Cu(CN)(MgCl)(2) and BuMgCl/CuX (X = CN, I; 10
      mol %) both in THF produced 2a with 93-94% regioselectivity in 87-92% yields. On
      the other hand, BuCu(CN)(MgX) in THF, Bu(2)Cu(CN)(MgX)(2) in Et(2)O, and
      BuMgX/CuCN (10 mol %) in Et(2)O furnished 3a in good yields with >90%
      selectively, irrespective of X of BuMgX. In the nickel-catalyzed butylation of 1
      with BuMgCl, NiCl(2)(dppp) among NiCl(2)(tpp)(2), NiCl(2)(dppf), and
      NiCl(2)(dppp) furnished the best result to produce 2a. The CuCN-based protocol
      was then applied to other alkyl Grignard reagents, which include Me, Et,
      (CH(2))(3)Ph, c-C(6)H(11), (CH(2))(6)OMOM, (CH(2))(9)CH=CH(2), and CH(2)Ph as the
      alkyl group (R(T)). In addition, the Mitsunobu inversion of 2a and 3a afforded
      the corresponding cis isomers stereoselectively with AcOH as an acid at -78
      degrees C in toluene for 2a and with 4-(NO(2))C(6)H(4)COOH in THF at r.t. for 3a.
      No racemization during the alkylation was confirmed by the reaction using (1R,3S)
      1 (>99% ee) to produce (1S,4S)-2a and (1S,2S)-3a, respectively.

PMID- 11511267
TI  - Density functional theory investigation of the reactions of isodihalomethanes
      (CH(2)X-X where X = Cl, Br, or I) with ethylene: substituent effects on the
      carbenoid behavior of the CH(2)X-X species.
AB  - We investigated the chemical reactions of isodihalomethane (CH(2)X-X) and CH(2)X
      radical species (where X = Cl, Br, or I) with ethylene and the isomerization
      reactions of CH(2)X-X using density functional theory calculations. The CH(2)X-X
      species readily reacts with ethylene to give the cyclopropane product and an X(2)
      product via a one-step reaction with barrier heights of approximately 2.9
      kcal/mol for CH(2)I-I, 6.8 kcal/mol for CH(2)Br-Br, and 8.9 kcal/mol for CH(2)Cl
      Cl. The CH(2)X reactions with ethylene proceed via a two-step reaction mechanism
      to give a cyclopropane product and X atom product with much larger barriers to
      reaction. This suggests that photocyclopropanation reactions using ultraviolet
      excitation of dihalomethanes most likely occurs via the isodihalomethane species
      and not the CH(2)X species. The isomerization reactions of CH(2)X-X had barrier
      heights of approximately 14.4 kcal/mol for CH(2)I-I, 11.8 kcal/mol for CH(2)Br
      Br, and 9.1 kcal/mol for CH(2)Cl-Cl. We compare our results for the CH(2)X-X
      carbenoids to results from previous calculations of the Simmons-Smith-type
      carbenoids (XCH(2)ZnX) and Li-type carbenoids (LiCH(2)X) and discuss their
      differences and similarities as methylene transfer agents.

PMID- 11511268
TI  - Computational support for tunneling in thermal[1,7]-hydrogen shift reactions.
AB  - Density functional calculations have been performed for the [1,7]-hydrogen shift
      in two substituted 1,3,5-heptatrienes (1 and 9) for which kinetic data are
      available from the literature, including the observed kinetic isotope effects.
      For both cases the computed kinetic isotope effect was significantly smaller than
      that observed. These results provide further support for the presence of
      tunneling in thermal, antarafacial [1,7]-hydrogen shift reactions.

PMID- 11511269
TI  - Lyconadin A, a novel alkaloid from Lycopodium complanatum.

PMID- 11511270
TI  - Duality of mechanism in the tetramethylfluoroformamidinium hexafluorophosphate
      mediated synthesis of N-benzyloxycarbonylamino acid fluorides.

PMID- 11511271
TI  - A convenient chiron for substituted cyclohexanones.

PMID- 11511272
TI  - First example of a Lewis acid-promoted [2+1] cycloaddition of a 1-thio-2
      silylethene.

PMID- 11511273
TI  - Synthesis of (13)C/D doubly labeled L-leucines: probes for conformational
      analysis of the leucine side-chain.

PMID- 11511274
TI  - Efficient Heck vinylation of aryl halides catalyzed by a new air-stable palladium
      tetraphosphine complex.

PMID- 11511275
TI  - A dinuclear strontium(II) complex as substrate-selective catalyst of ester
      cleavage.

PMID- 11511276
TI  - Rhodium-catalyzed regio- and stereoselective addition of diphenylphosphine oxide
      to alkynes.

PMID- 11511277
TI  - Highly stereoselective route to dialkyl sulfoxides based upon the sequential
      displacement of oxygen and carbon leaving groups by Grignard reagents on sulfinyl
      compounds.

PMID- 11511278
TI  - Investigation of elimination reactions of 7-oxabicyclo[2.2.1]heptane-2
      carboxylates.

PMID- 11511279
TI  - A new modular class of easily accessible, inexpensive, and efficient chiral
      diphosphine ligands for homogeneous stereoselective catalysis.

PMID- 11511280
TI  - On the quantitative analysis of diplopic strabismus 1881.

PMID- 11511282
TI  - Evidence based medicine: a fad? A fraud? A tool? Good, bad or just plain evil?
      Hirschberg's legacy; superior oblique weakening; stiff necks; CPEO.

PMID- 11511283
TI  - Graded recessions of the superior oblique muscle: biomechanical analysis of their
      effects upon its vertical, torsional and horizontal force components.
AB  - PURPOSE: To obtain objective information about the effects of different amounts
      and directions of superior oblique muscle (SO) recession, on its three force
      components: torsional (incyclotorsion), vertical (depression), and horizontal
      (abduction). METHODS: A well known Biomechanical Model of Ocular Motility (Orbit
      1.8 Gaze Mechanics Simulation), was used to simulate different amounts of
      recession of the superior oblique muscle, along three different and commonly used
      axes of recession: a) along its anatomical path (the hypothetical line uniting
      the trochlea and the scleral insertion of the SO); b) anteroposteriorly on the
      nasal side of the superior rectus muscle (recession with posterior
      transposition); and c) straightforward nasal transposition around the globe.
      Changes in its force fraction components (torsional, vertical and horizontal)
      were obtained from the "Mechanical State Viewer" of Orbit, for each amount of
      recession in three gaze positions: in and down (infra-adduction), downgaze, and
      out and down (infra-abduction). Several graphics were created with these data for
      comparison of results. RESULTS: Any one of the axes of simulated recession of the
      SO proved to be effective in changing the main actions of the muscle in the gaze
      positions that were analyzed. The effects upon any one of the oblique muscle
      force components, were typical for any type of recession, as would be expected
      from its relationships to the three axes of rotation of the globe. Significant
      differences were noted among procedures when progressivity of effects, according
      to the amount of the simulated recession, was analyzed. Qualitative changes in
      one or more of the force components of the SO were also found with some
      procedures and amounts of recession, thus confirming some complications reported
      in the literature. CONCLUSIONS: A separate analysis of the effects of surgery
      upon any one of the three force components of the SO can best be obtained with
      the help of biomechanical models of ocular motility as the one herein tested.
      Such an analysis may help dilucidate the most convenient point of recession of
      the SO, when seeking for a specific effect (torsional, vertical or horizontal)
      along with a minimization of the effects upon the rest of them.

PMID- 11511284
TI  - Vision loss associated with a stiff neck complicating strabismus surgery.
AB  - An exotropic 60 year old suffered a scleral-choroidal penetration and vitreous
      hemorrhage during and after strabismus surgery on a highly myopic eye when her
      anesthetic airway management was complicated by her previously asymptomatic and
      unrecognized rigid cervical spine which placed both the surgeon and the
      anesthetist in disadvantaged positions both physically and medically. Restoration
      of vision and binocularity ultimately required vitrectomy and intraocular lens
      implantation.

PMID- 11511285
TI  - Congenital mitochondrial cytopathy and chronic progressive external
      ophthalmoplegia.
AB  - BACKGROUND: Chronic Progressive External Ophthalmoplegia (CPEO) encompasses
      different conditions having in common a slowly progressive external and general
      ophthalmoplegia. The discovery of CPEO is suggestive of mitochondrial cytopathy,
      but this is not necessarily so. CASE REPORT: We report here a case, presenting at
      age 9 months, characterized by bilateral blepharoptosis and partial third nerve
      oculomotor deficiency, with no nystagmus. Mitochondrial cytopathy was suspected
      on cranial MRI and confirmed by muscle biopsy. Enzyme studies revealed a defect
      on the complex I respiratory chain. This case is unique in that the symptoms
      completely resolved under a Ketogen diet.

PMID- 11511286
TI  - Grand rounds #63: a case of a bilateral gaze limitation with diplopia for reading
      after two surgical procedures to treat a right medical rectus muscle paresis.

PMID- 11511287
TI  - Atropine and bifocals can slow the progression of myopia in children.
AB  - BACKGROUND: Atropine 1% ophthalmic solution has been used to retard progression
      of simple childhood myopia. Problems have been identified in previous studies,
      including possible observer bias. To address this issue, we evaluated our
      experience including the duration that atropine maintains a child at 20/30 or
      better in one spectacle correction compared with controls. METHODS: Fifteen
      myopic children who received daily atropine 1% ophthalmic solution bilaterally
      for a mean of 29.3 months (range 3-96) were compared to a control group of 15
      unrelated similar myopic patients. The progression of myopia, change of glasses,
      patient demographics, and any side effects or complaints were recorded. RESULTS:
      The mean annual myopic progression in the atropine group was 0.05 diopters (D)
      (+/-0.67) and in the control group 0.84 D (+/-0.26)(P=0.00021). The number of
      months that vision remained 20/30 or better using the same pair of glasses was
      25.1 (+/-19.3) for the atropine group and 13.5 (+/-10.3) for the control group
      (P=0.049). Mean followup time was 29 months for the atropine group and 42.6
      months for the control group. There were no statistical differences between the
      two groups regarding sex, age, or age at first glasses. CONCLUSIONS: Atropine
      ophthalmic solution nearly halted myopic progression in this investigation.
      Patients on atropine remained 20/30 or better with a single pair of glasses
      significantly longer than the control group. While a larger and better controlled
      study is desirable, atropine appears to be a viable method to retard myopic
      progression.

PMID- 11511288
TI  - Treatment of childhood myopia with atropine eyedrops and bifocal spectacles.
AB  - BACKGROUND: Animal and human studies have suggested that muscarinic antagonists
      and bifocal spectacles may decrease the progression of myopia in children. The
      purpose of this study is to report the largest known series of patients treated
      simultaneously with bifocals and topical atropine. DESIGN: Retrospective,
      interventional, non-comparative case series. METHODS: 706 myopic children (296
      boys and 410 girls, ages 6 to 16 years) were prescribed full cycloplegic
      spectacle corrections, with photochromic lenses and +2.25 diopter (D) reading
      adds in each eye. Both eyes were treated with atropine 1% drops once daily.
      OUTCOME MEASURES: Annual change in cycloplegic refractions of right eyes.
      Compliance with therapy was monitored by patient and parental report. RESULTS:
      496 (70%) of the 706 patients reported full compliance with the treatment
      regimen, whereas the remaining 210 (30%) patients were partially compliant. The
      median interval of treatment was 3.62 years (range, 21 days-10.1 years). The mean
      rate of myopic progression was significantly less (P<0.001) in patients who were
      fully compliant with atropine therapy and bifocals (0.08 D/year) than in patients
      who were partially compliant with the treatment regimen (0.23 D/per year). No
      serious adverse effects were associated with atropine therapy. CONCLUSIONS: Full
      compliance with topical atropine therapy and bifocal spectacles was associated
      with decreased progression of myopia compared to partial compliance with
      treatment. For each of the treated groups, the mean rate of myopic progression
      was significantly less (P<0.05) than the mean annual rates of myopic progression
      published for the pediatric population.

PMID- 11511291
TI  - A new strategy for modulating chemotherapy-induced alopecia, using PTH/PTHrP
      receptor agonist and antagonist.
AB  - Parathyroid hormone (PTH) related peptide (PTHrP) and the PTH/PTHrP receptor
      (PTH/PTHrP-R) show prominent cutaneous expression, where this signaling system
      may exert important paracrine and/or autocrine functions, such as in hair growth
      control. Chemotherapy-induced alopecia - one of the fundamental unsolved problems
      of clinical oncology - is driven in part by defined abnormalities in hair
      follicle cycling. We have therefore explored the therapeutic potential of a
      PTH/PTHrP-R agonist and two PTH/PTHrP-R antagonists in a mouse model of
      cyclophosphamide-induced alopecia. Intraperitoneal administration of the agonist
      PTH(1-34) or the antagonists PTH(7-34) and PTHrP(7-34) significantly altered the
      follicular response to cyclophosphamide in vivo. PTH(7-34) and PTHrP(7-34)
      shifted it towards a mild form of "dystrophic anagen", associated with a
      significant reduction in apoptotic (TUNEL+) hair bulb cells, thus mitigating the
      degree of follicle damage and retarding the onset of cyclophosphamide-induced
      alopecia. PTH(1-34), in contrast, forced hair follicles into "dystrophic
      catagen", associated with enhanced intrafollicular apoptosis. We had previously
      shown that an induced shift in the follicular damage-response towards "dystrophic
      catagen" mitigates cyclophosphamide-induced alopecia, whereas a shift towards
      "dystrophic catagen" initially enhanced the hair loss, yet subsequently promoted
      accelerated hair follicle recovery. Therefore, this study in an established
      animal model of chemotherapy-induced alopecia, which closely mimics human
      chemotherapy-induced alopecia, strongly encourages the exploration of PTH/PTHrP-R
      agonists and antagonists as novel therapeutic agents in chemotherapy-induced
      alopecia.

PMID- 11511292
TI  - The spectrum of pathogenic mutations in SPINK5 in 19 families with Netherton
      syndrome: implications for mutation detection and first case of prenatal
      diagnosis.
AB  - The Comel-Netherton syndrome is an autosomal recessive multisystemic disorder
      characterized by localized or generalized congenital ichthyosis, hair shaft
      abnormalities, immune deficiency, and markedly elevated IgE levels. Life
      threatening complications during infancy include temperature and electrolyte
      imbalance, recurrent infections, and failure to thrive. To study the clinical
      presentations of the Comel-Netherton syndrome and its molecular cause, we
      ascertained 19 unrelated families of various ethnic backgrounds. Results of
      initial linkage studies mapped the Comel-Netherton syndrome in 12 multiplex
      families to a 12 cM interval on 5q32, thus confirming genetic homogeneity of
      Comel-Netherton syndrome across families of different origins. The Comel
      Netherton syndrome region harbors the SPINK5 gene, which encodes a multidomain
      serine protease inhibitor (LEKTI) predominantly expressed in epithelial and
      lymphoid tissues. Recently, recessive mutations in SPINK5 were identified in
      several Comel-Netherton syndrome patients from consanguineous families. We used
      heteroduplex analysis followed by direct DNA sequencing to screen all 33 exons
      and flanking intronic sequences of SPINK5 in the affected individuals of our
      cohort. Mutation analysis revealed 17 distinct mutations, 15 of which were novel,
      segregating in 14 Comel-Netherton syndrome families. The nucleotide changes
      included four non-sense mutations, eight small deletions or insertions leading to
      frameshift, and five splice site defects, all of which are expected to result in
      premature terminated or altered translation of SPINK5. Almost half of the
      mutations clustered between exons 2 and 8, including two recurrent mutations.
      Genotype-phenotype correlations suggested that homozygous nucleotide changes
      resulting in early truncation of LEKT1 are associated with a severe phenotype.
      For the first time, we used molecular data to perform prenatal testing, thus
      demonstrating the feasibility of molecular diagnosis in the Comel-Netherton
      syndrome.

PMID- 11511293
TI  - CC chemokine receptor 4 expression on peripheral blood CD4+ T cells reflects
      disease activity of atopic dermatitis.
AB  - Recent studies indicate that Th1 and Th2 cells differ in their chemokine receptor
      expression and their responsiveness to various chemokines. Therefore, selective
      Th2 cell recruitment in Th2-predominant inflammatory diseases such as atopic
      dermatitis may be under the influence of some chemokines. It is reported that CC
      chemokine receptor (CCR) 4 is selectively expressed on Th2 cells whereas CXC
      chemokine receptor (CXCR) 3 is selectively expressed on Th1 cells. In this study
      we examined CCR4 and CXCR3 expression on peripheral blood CD4+ and CD8+ T cells
      obtained from adult atopic dermatitis subjects, and compared the results with
      those from patients with psoriasis vulgaris and healthy controls. CCR4 was
      preferentially expressed on CD4+ T cells from atopic dermatitis subjects and
      CXCR3 was preferentially expressed on CD4+ T cells from psoriasis vulgaris
      subjects. This CCR4 expression was prominent especially in severe atopic
      dermatitis subjects. CCR4 expression on CD4+ T cells in severe atopic dermatitis
      subjects decreased on improvement of disease activity. CD25 was preferentially
      expressed on CCR4+CD4+ T cells but not on CXCR3+CD4+ T cells in atopic dermatitis
      subjects. Cutaneous lymphocyte-associated antigen was also preferentially
      expressed on CCR4+CD4+ T cells but not on CXCR3+CD4+ T cells in atopic dermatitis
      subjects. CD4+ T cells in atopic dermatitis skin lesions were predominantly CCR4+
      cells. Taken together, this study strongly indicates that CCR4+CD4+ T cells
      reflect disease activity and suggests that CCR4 expression is important for T
      cell infiltration into atopic dermatitis lesions. Thus, CCR4 may be a possible
      target for therapy of atopic dermatitis in the future.

PMID- 11511294
TI  - A stop codon in xeroderma pigmentosum group C families in Turkey and Italy:
      molecular genetic evidence for a common ancestor.
AB  - Xeroderma pigmentosum family G from Van, Turkey had two severely affected
      children: a son with multiple skin cancers who died at age 10 (XP67TMA), and an 8
      y old daughter who began developing skin cancer before 3 y of age (XP68TMA).
      XP67TMA and XP68TMA cells were hypersensitive to killing by ultraviolet and the
      post-ultraviolet DNA repair level was 12-16% of normal. Host cell reactivation of
      an ultraviolet-treated reporter plasmid cotransfected with a vector expressing
      wild-type XPC cDNA assigned XP67TMA to xeroderma pigmentosum complementation
      group C. The XPC mRNA level was markedly reduced. Sequencing of the 3.5 kb XPC
      cDNA from XP67TMA showed a C-T mutation in XPC exon 8 at base pair 1840. This
      mutation converts the CGA codon of arginine at amino acid 579 to a UGA stop codon
      resulting in marked truncation of the 940 amino acid xeroderma pigmentosum C
      protein. Restriction fragment length polymorphism analysis of XPC exon 8 DNA in
      XP67TMA and XP68TMA showed that both affected children had a homozygous mutation
      and that both parents had heterozygous normal and mutated sequences at the same
      position consistent with a history of consanguinity in the family. The mutated
      allele also contained two XPC single nucleotide polymorphisms. The same mutated
      XPC allele was reported in an Italian family. Studies of 19 microsatellite
      markers flanking the XPC gene on chromosome 3 suggest that the XPC allele passed
      between Italy and Turkey approximately 300-500 y ago. This XPC allele containing
      a nonsense mutation is associated with severe clinical disease with multiple skin
      cancers and early death.

PMID- 11511295
TI  - A mannose-binding receptor is expressed on human keratinocytes and mediates
      killing of Candida albicans.
AB  - Human keratinocytes are known to kill Candida albicans in vitro, but the
      mechanism of killing is not yet understood. Here, we demonstrate that
      spontaneous, ultraviolet-B-light-induced, alpha-melanocyte-stimulating-hormone
      induced, and interleukin-8-induced Candida killing by keratinocytes can be
      inhibited with mannan and mannosylated bovine serum albumin (Man-BSA). A
      polyclonal goat serum raised against the human macrophage mannose receptor
      stained suprabasal keratinocytes, but no staining was observed on keratinocytes
      with a monoclonal antibody (mAb15) specific for the human macrophage mannose
      receptor. Mannose-affinity chromatography of keratinocyte extract isolated a 200
      kDa protein, and on the Western blot the goat antiserum reacted with a 200 kDa
      protein. In radioligand binding studies, the binding of 125I-Man-BSA to human
      keratinocytes was inhibited by mannan in a concentration-dependent manner.
      Analysis of the binding revealed a single class keratinocyte mannose receptor
      with a KD of 1.4 x 10(-8) M and a Bmax of 1 x 10(4) binding sites per cell. The
      binding of 125I-Man- BSA to keratinocytes proved to be time-dependent, acid
      precipitable, and Ca2+- and trypsin-sensitive. After trypsinization the receptors
      underwent a rapid recovery at 37 degrees C. These results demonstrate the
      presence of mannose receptor on human keratinocytes, and its active involvement
      in the killing of Candida albicans.

PMID- 11511296
TI  - Novel mutations of the transglutaminase 1 gene in lamellar ichthyosis.
AB  - Lamellar ichthyosis, one form of congenital autosomal recessive ichthyosis, is
      caused by mutations in the gene (TGM1) encoding the transglutaminase 1 enzyme.
      Mutations, deletions, or insertion of TGM1 have been reported so far. Here we
      report that three novel mutations of TGM1, D101V, N288T, and R306W, cause
      lamellar ichthyosis in two different families. The patient in family LI-KD has
      N288T and R306W mutations, and the patient in family LI-LK has D101V and R306W
      mutations. The activity of the transglutaminase 1 enzyme of the patient in family
      LI-LK was only about 15% of normal. Also, three-dimensional structural prediction
      analyses revealed that the N288T and R306W mutations, and possibly the D101V
      mutation, cause misfolding in the central catalytic core domain of the
      transglutaminase 1 enzyme that would probably result in reduced enzyme activity.
      Our data suggest that the greatly reduced transglutaminase 1 activities are due
      to disruptions of the native folding of transglutaminase 1, and that these
      mutations may play a critical role in the pathology of lamellar ichthyosis.

PMID- 11511297
TI  - Ultraviolet irradiation increases matrix metalloproteinase-8 protein in human
      skin in vivo.
AB  - Humans express three distinct collagenases, MMP-1, MMP-8, and MMP-13, that
      initiate degradation of fibrillar type I collagen. We have previously reported
      that ultraviolet irradiation causes increased expression of MMP-1, but not MMP
      13, in keratinocytes and fibroblasts in human skin in vivo. We report here that
      ultraviolet irradiation increases expression of MMP-8 in human skin in vivo.
      Western analysis revealed that levels of the full-length, 85 kDa proenzyme form
      of MMP-8 increased significantly within 8 h post ultraviolet irradiation (2
      minimal erythema doses). Increased full-length MMP-8 protein was associated with
      infiltration into the skin of neutrophils, which are the major cell type that
      expresses MMP-8. Immunofluorescence revealed coexpression of MMP-8 and neutrophil
      elastase, a marker for neutrophils. Immunohistology demonstrated MMP-8 expression
      in neutrophils in the papillary dermis between 4 and 8 h post ultraviolet
      irradiation, and in the epidermis at 24 h post radiation. MMP-8 mRNA expression
      was not detected in nonirradiated or ultraviolet-irradiated human skin,
      indicating that increased MMP-8 following ultraviolet irradiation resulted from
      preexisting MMP-8 protein in infiltrating neutrophils. Pretreatment of skin with
      the glucocorticoid clobetasol, but not all-trans retinoic acid, significantly
      blocked ultraviolet-induced increases in MMP-8 protein levels, and neutrophil
      infiltration. In contrast, all-trans retinoic acid and clobetasol were equally
      effective in blocking ultraviolet induction of MMP-1 and degradation of collagen
      in human skin in vivo. Taken together, these data demonstrate that ultraviolet
      irradiation increases MMP-8 protein, which exists predominantly in a latent form
      within neutrophils, in human skin in vivo. Although ultraviolet irradiation
      induces both MMP-1 and MMP-8, ultraviolet-induced collagen degradation is
      initiated primarily by MMP-1, with little, if any, contribution by MMP-8.

PMID- 11511298
TI  - Human dermal fibroblasts express prohormone convertases 1 and 2 and produce
      proopiomelanocortin-derived peptides.
AB  - In the last few years it has become apparent that the skin is a locoregional
      source for several proopiomelanocortin-derived peptides including alpha
      melanocyte-stimulating hormone, adrenocorticotropin, and beta-endorphin. The
      enzymes that regulate expression of these neuropeptides are the prohormone
      convertases 1 and 2. In this study we demonstrate, by reverse transcriptase
      polymerase chain reaction and Western immunoblotting, that cultured human dermal
      fibroblasts express prohormone convertases 1 and 2 as well as 7B2, which is an
      essential cofactor for enzymatic activity of prohormone convertase 2.
      Immunofluorescence studies revealed prohormone convertase 1 to be mainly
      expressed in the perinuclear region in vesicular structures resembling the trans
      Golgi network, whereas prohormone convertase 2 was found in the trans-Golgi
      network as well as in vesicular structures diffusely distributed in the
      peripheral cytoplasm. Expression of both enzymes was also confirmed in
      fibroblasts of normal adult human skin by immunohistochemistry using antibodies
      against prohormone convertases 1 and 2 and vimentin. To assess the relevance of
      prohormone convertase 1 and 2 expression in human dermal fibroblasts, we studied
      the expression of proopiomelanocortin and proopiomelanocortin-derived peptides.
      Proopiomelanocortin expression was detected by reverse transcriptase polymerase
      chain reaction and Western immunoblotting. Alpha-melanocyte-stimulating hormone,
      adrenocorticotropin, and beta-endorphin were mainly located in vesicular
      structures as demonstrated by immunofluorescence. Production of these peptides
      was confirmed by radioimmunoassay, immunoradiometric assay, or enzyme
      immunoassay. Among several stimuli tested, interleukin-1 was found to upregulate
      production of alpha-melanocyte-stimulating hormone in human dermal fibroblasts.
      In summary, we have shown that human dermal fibroblasts express the enzymatic
      machinery for proopiomelanocortin processing and make proopiomelanocortin, alpha
      melanocyte-stimulating hormone, adrenocorticotropin, and beta-endorphin.
      Production of proopiomelanocortin peptides by human dermal fibroblasts may be
      relevant for fibroblast functions such as collagen degradation and/or regulation
      of dermal immune responses.

PMID- 11511299
TI  - Production and pharmacologic modulation of the granulocyte-associated allergic
      responses to ovalbumin in murine skin models induced by injecting ovalbumin
      specific Th1 or Th2 cells.
AB  - Because interferon-gamma, interleukin-4, and interleukin-5 have been identified
      at the mRNA and protein levels in the lesional skin of patients with atopic
      dermatitis, we investigated the roles played by granulocytes as effector cells in
      allergic inflammation by using two unique murine skin models. In vitro generated
      Th1 and Th2 cells from naive splenocytes of antiovalbumin T cell receptor
      transgenic BALB/C mice were adoptively transferred with ovalbumin into the ear
      pinnae or air-pouches produced in the back skin of naive, nontransgenic BALB/C
      mice. The injection of Th1 cells with ovalbumin induced delayed type ear swelling
      that peaked at 48 h, whereas that of Th2 resulted in ear swelling that peaked at
      a much earlier time, 24 h. Histologic study of the swollen ear skin and
      granulocytes recruited into the air-pouch demonstrated that, although the Th1
      induced inflammation caused a neutrophil-predominant infiltrate with few
      eosinophils, larger numbers of eosinophils accumulated in the Th2-induced
      inflammation. Using these murine models, we further evaluated the effects of
      drugs used for the treatment of atopic diseases. The results showed that FK506
      administration could effectively reduce skin inflammation induced by either Th
      cells. Interestingly, the neutrophil elastase inhibitor ONO-6818 efficiently
      inhibited Th1-induced inflammation. In contrast, a leukotriene receptor
      antagonist, ONO-1078, specifically suppressed Th2-induced inflammation. We also
      found that each ONO drug exerted direct influence on specified granulocytes, as
      neither affected in vitro production of relevant Th cytokines. Thus, we succeeded
      in developing animal skin inflammation models in which we can evaluate the
      contribution of protein antigen-specific Th1 or Th2 cells through the action of
      granulocytic effector cells.

PMID- 11511300
TI  - Subcutaneous adipocytes promote the differentiation of squamous cell carcinoma
      cell line (DJM-1) in collagen gel matrix culture.
AB  - Cancer cell-stromal cell interaction plays a crucial role in the malignant growth
      of cancer cells. In the skin, the main stromal cell types consist of dermal
      fibroblasts and subcutaneous adipocytes. Fibroblasts are shown to promote the
      invasive growth of various cancer cell types. The interaction between cancer
      cells and stromal adipocytes, however, has not been sufficiently studied even in
      cutaneous carcinoma. To address the effects of adipocytes on the biologic
      behavior of cancer cells, we examined the growth and differentiation of a
      squamous cell carcinoma cell line of the skin (DJM-1), using a three-dimensional
      collagen gel matrix culture with a cutaneous environmental factor, air exposure.
      The growth was estimated by the uptake of bromodeoxy-uridine (BrdU) for 24 h. The
      BrdU indices of DJM-1 cells in stromal-cell-free, fibroblast-containing, and
      adipocyte- containing conditions were 19.7 +/- 1.9%, 19.8 +/- 2.8%, and 4.7 +/-
      1.4%, respectively, whereas the BrdU index on the gel containing both fibroblasts
      and adipocytes was 10.4 +/- 3.3%. In terms of differentiation, DJM-1 cells
      cocultured with adipocytes constructed the best-organized stratified layer with a
      cornified-like structure in all conditions above. The differentiation markers
      involucrin and cytokeratin 10 were immunohistochemically detected in this
      structure of DJM-1 cells. Adipocyte-induced phenomena were not affected
      distinctively by air exposure. These results indicate that adipocytes, but not
      fibroblasts, promote the differentiation of squamous cell carcinoma cells (DJM-1)
      and inhibit their growth. These adipocyte-induced phenomena were not completely
      inhibited by fibroblasts. In conclusion, we suggest that stromal adipocytes may
      be involved in the differentiating mechanisms of cutaneous carcinoma cells.

PMID- 11511301
TI  - Polymorphisms in glutathione S-transferases are associated with altered risk of
      nonmelanoma skin cancer in renal transplant recipients: a preliminary analysis.
AB  - Non-melanoma skin cancer (NMSC) represents a significant cause of morbidity and
      mortality among renal transplant recipients, with tumors behaving more
      aggressively than those in nontransplant patients. Not all immunosuppressed
      patients develop NMSC, however, and in those that do, the rate of accrual and
      numbers of lesions vary considerably. Though ultraviolet light is critical, it is
      unlikely that this alone explains the observed phenotypic diversity, suggesting
      the possible involvement of genetic factors. Furthermore, although twin studies
      in nontransplant patients with NMSC suggest a low genetic component, several
      genes associated with susceptibility and outcome in these patients have been
      identified. Thus, having previously shown that polymorphism in members of the
      glutathione S-transferase (GST) supergene family is associated with altered NMSC
      risk in nontransplant patients, we examined allelism in GSTM1, GSTP1, GSTM3, and
      GSTT1 in 183 renal transplant recipients. GSTM1 null was associated with
      increased squamous cell carcinoma (SCC) risk (p = 0.042, OR = 3.1). This remained
      significant after correction for age, gender, and ultraviolet light exposure (p =
      0.012, OR = 8.4) and was particularly strong in patients with higher ultraviolet
      light exposure (e.g., sunbathing score > 3, p = 0.003, OR = 11.5) and in smokers
      (p = 0.021, OR = 4.8). Analysis of the interaction between GSTM1 null and
      sunbathing score showed that the two factors were synergistic and individuals
      with both risk parameters demonstrated a shorter time from transplantation to
      development of the first SCC (p = 0.012, hazard ratio = 7.1). GSTP1*Ile
      homozygotes developed larger numbers of SCC (p = 0.002, rate ratio = 7.6),
      particularly those with lower ultraviolet light exposure and cigarette
      consumption. GSTM3 and GSTT1 also demonstrated significant associations, though
      some genotype frequencies were low. These preliminary data suggest that genetic
      factors mediating protection against oxidative stress are important in NMSC
      development in immunosuppressed patients and may be useful in identifying high
      risk individuals.

PMID- 11511302
TI  - Change of ultraviolet absorbance of sunscreens by exposure to solar-simulated
      radiation.
AB  - Regarding the outdoor behavior of the Caucasian population, modern sunscreens
      should provide high and broad-spectrum ultraviolet protection in the ultraviolet
      B as well as in the ultraviolet A range and should be photochemically stable for
      ultraviolet doses, which can be expected in solar radiation. At present an
      assessment of the photostability of suncare products is not a general requirement
      before marketing. In order to evaluate the photostability of suncare products we
      conducted an in vitro test and measured the spectral absorbance of 16 sunscreens
      before, and after exposure to increasing biologically weighted standard erythema
      doses (5, 12.5, 25, 50) of solar-simulated radiation. Seven of 16 suncare
      products showed a significant dose- and wavelength-dependent decrease of the
      ultraviolet A protective capacity, whereas the ability to absorb ultraviolet B
      was not affected. In the ultraviolet A range, the decrease of absorbance
      (photoinactivation), respectively, the increase of transmission was 12-48% for an
      ultraviolet exposure of 25 standard erythema dose. Photoinactivation started in
      the wavelength range between 320 and 335 nm with a maximum above 350 nm.
      Furthermore, our analysis showed that the behavior of suncare products was not
      predictable from its individual ingredients. Neither complex combinations of
      organic filters nor addition of inorganic filters could absolutely prevent
      photoinactivation. The inclusion of a single photounstable filter did not mean
      photoinstability of the complete suncare product. Photoinactivation of sunscreens
      appears to be an underestimated hazard to the skin, first, by formation of free
      radicals, second, by increased ultraviolet A transmission.

PMID- 11511303
TI  - Cyclobutane thymidine dimers are present in human urine following sun exposure:
      quantitation using 32P-postlabeling and high-performance liquid chromatography.
AB  - Cyclobutane thymidine dimer (T=T) is the major DNA photoproduct formed in human
      skin after solar radiation. We have developed a 32P-postlabeling method suitable
      for quantitating T=T in human urine with a detection limit of about 0.5 fmol per
      10 microl urine. The method was used in the present study to measure the daily
      T=T urinary level of two volunteers over a 15 d period, including frequent sun
      exposures ranging from 0 to 5 h daily. T=T was not detected before or immediately
      (4 h) after the initial sun exposure but was first observed in urine samples
      collected 18 h after the initial exposure. Thereafter, urinary T=T levels
      gradually increased up to a peak reached about 3 d after the maximum sun
      exposure. The levels decreased during the following days but were still
      detectable 8 d after the last sun exposure. About 70-75% decrease in excreted T=T
      was observed after 8 d. The T=T levels measured in urine were lower but in the
      same order of magnitude as the levels expected after a theoretical calculation
      based on previous published results and reasonable assumptions. This study shows
      the occurrence of cyclobutane thymidine dimers in human urine after skin exposure
      to solar radiation.

PMID- 11511304
TI  - Different pattern of collagen cross-links in two sclerotic skin diseases:
      lipodermatosclerosis and circumscribed scleroderma.
AB  - Changes in the process of cross-linking of collagen molecules are associated with
      defects in the biomechanical stability of the extracellular matrix. Fibrosis of
      skin is characterized by an increase in pyridinolines, which are hydroxylysine
      aldehyde derived cross-links usually absent in healthy skin. In this study, we
      analyzed cross-links in lipodermatosclerosis and localized scleroderma to address
      the question whether all the mature cross-links currently characterized are
      increased in fibrosis in addition to the increase in pyridinolines. As psoralen
      plus ultraviolet A treatment leads to clinical improvement of fibrotic plaques in
      localized scleroderma we analyzed the cross-link content in lesional skin after
      bath psoralen plus ultraviolet A therapy. In skin from patients with localized
      scleroderma an increase in the total number of mature cross-links was found to be
      due to an increase in both pyridinolines and dehydro
      histidinohydroxymerodesmosine. The concentration of
      histidinohydroxylysinonorleucine was unchanged. By contrast, the total number of
      mature cross-links was decreased in lipodermatosclerosis. This decrease was
      caused by a decrease of lysine aldehyde derived cross-links (dehydro
      histidinohydroxymerodesmosine and histidinohydroxylysinonorleucine), whereas the
      concentration of pyridinolines increased. A decrease in the content of
      pyridinolines after bath psoralen plus ultraviolet A treatment was found in six
      out of nine patients with localized scleroderma, which might reflect a remodeling
      of the extracellular matrix. Our data provide evidence that sclerosis of skin is
      associated with either an increase in the number of cross-links per molecule of
      collagen or a change in the molecular nature of the cross-links formed.

PMID- 11511305
TI  - 17beta-estradiol, progesterone, and dihydrotestosterone suppress the growth of
      human melanoma by inhibiting interleukin-8 production.
AB  - We studied the effects of 17beta-estradiol, progesterone, and dihydrotestosterone
      on in vitro growth of human metastatic melanoma. Each sex hormone inhibited the
      growth of melanoma receptor-dependently; 17beta-estradiol inhibited 3H-thymidine
      uptake of estrogen receptor-positive WM266-4 and NM26, but not that of the
      receptor-negative HS15. Progesterone inhibited 3H-thymidine uptake of
      progesterone receptor-positive WM266-4 and HS15, but not that of the receptor
      negative NM26. Dihydrotestosterone inhibited 3H-thymidine uptake of androgen
      receptor-positive HS15 and NM26, but not that of the receptor-negative WM266-4.
      The growth inhibition by each hormone was counteracted by the respective hormone
      receptor antagonist. The combination of more than two hormones neither gave
      additive nor synergistic growth inhibition. The growth inhibition by each sex
      hormone was counteracted by interleukin-8 but not by the other growth factors.
      Each sex hormone reduced the constitutive interleukin-8 secretion and mRNA levels
      in the respective receptor-positive melanoma but not in the receptor-negative
      melanoma. Transient transfection showed that each sex hormone inhibited the
      constitutive chloramphenicol acetyltransferase expression driven by interleukin-8
      promoter in the respective receptor-positive melanoma but not in the receptor
      negative melanoma. Transfection with a series of 5'-deleted interleukin-8
      promoter/chloramphenicol acetyltransferase reporter constructs demonstrated that
      the sequences between -98 and -63 bp on interleukin-8 promoter may be involved in
      the transcriptional repression. These data suggest that 17beta-estradiol,
      progesterone, and dihydrotestosterone suppress the growth of melanoma by
      inhibiting interleukin-8 production in a receptor-dependent manner.

PMID- 11511306
TI  - Gangliosides GD1b, GT1b, and GQ1b suppress the growth of human melanoma by
      inhibiting interleukin-8 production: the inhibition of adenylate cyclase.
AB  - We studied the effects of various gangliosides on in vitro growth of human
      metastatic melanoma WM266-4. GD1b, GT1b, and GQ1b inhibited 3H-thymidine uptake
      and growth rate of WM266-4 whereas the other gangliosides were ineffective. The
      growth inhibition by GD1b, GT1b, and GQ1b was counteracted by interleukin-8 but
      not by the other growth factors. The growth inhibition by gangliosides was not
      detected in the presence of anti-interleukin-8 antibody. GD1b, GT1b, and GQ1b
      reduced the constitutive interleukin-8 secretion and mRNA levels in WM266-4.
      Transient transfection showed that GD1b, GT1b, and GQ1b inhibited the
      constitutive chloramphenicol acetyltransferase expression driven by interleukin-8
      promoter in WM266-4. Transfection with a series of 5'-deleted mutants
      demonstrated that the sequences between -98 and -62 bp on interleukin-8 promoter
      may be involved in the transcriptional repression by these gangliosides. Cyclic
      AMP analog dibutyryl cAMP counteracted GD1b, GT1b, and GQ1b-induced inhibition of
      interleukin-8 production at the levels of protein secretion, mRNA expression, and
      promoter activity. GD1b, GT1b, and GQ1b reduced cAMP level and protein kinase A
      activity in WM266-4. These gangliosides suppressed adenylate cyclase activity
      without altering that of cyclic nucleotide phosphodiesterase in WM266-4. The data
      indicate that GD1b, GT1b, and GQ1b may suppress the growth of melanoma by
      inhibiting interleukin-8 production via the inhibition of adenylate cyclase.

PMID- 11511307
TI  - Melanocortin 1 receptor (MC1R) gene variants are associated with an increased
      risk for cutaneous melanoma which is largely independent of skin type and hair
      color.
AB  - Individuals carrying melanocortin 1 receptor gene variants have an increased risk
      for the development of cutaneous melanoma. Melanocortin 1 receptor gene variants
      are also associated with other risk factors for melanoma such as fair skin and
      red hair. We evaluated the relationship of melanocortin 1 receptor gene variants,
      fair skin, red hair and the development of melanoma in 123 patients with
      cutaneous melanoma and 385 control subjects. To analyze the association between
      melanocortin 1 receptor gene variants and skin type or hair color we also made
      use of 453 patients with nonmelanoma skin cancer. We analyzed the coding sequence
      of the melanocortin 1 receptor gene region by single-stranded conformation
      polymorphism analysis, followed by DNA sequence analysis. Risk of melanoma
      dependent on the various melanocortin 1 receptor variant alleles was estimated by
      exposure odds ratios. The analyses of all different melanocortin 1 receptor gene
      variants combined, showed that the presence of melanocortin 1 receptor gene
      variants amounted to a higher melanoma risk, which, in stratified analyses, was
      independent of skin type and hair color. The odds ratios after adjusting for skin
      type were 3.6 (95% CI 1.7-7.2) for two variants and 2.7 (95% CI 1.5-5.1) for one
      variant, respectively. Compound heterozygotes and homozygotes for the Val60Leu,
      Val92Met, Arg142His, Arg151Cys, Arg160Trp, Arg163Gln, and His260Pro variants had
      odds ratios of about 4 to develop melanoma, whereas heterozygotes for these
      variants had half the risk. The presence of the melanocortin 1 receptor gene
      variant Asp84Glu appeared to impose the highest risk for cutaneous melanoma with
      odds ratios of 16.1 (95% CI 2.3-139.0) and 8.1 (95% CI 1.2-55.9) in compound
      heterozygotes and heterozygotes, respectively. The broad confidence intervals,
      when the different variants were analyzed separately, however, do not allow
      drawing definite conclusions about the magnitude of these risks. Of the more
      frequently occurring melanocortin 1 receptor variant alleles the Asp84Glu,
      Arg142His, Arg151Cys, Arg160Trp, His260Pro, and Asp294His variants were strongly
      associated with both fair skin and red hair. The Val60Leu, Val92Met, and
      Arg163Gln variant alleles, however, were only weakly or not associated with fair
      skin type and/or red hair, which further illustrates the finding that skin type,
      hair color, and melanoma are independent outcomes of the presence of melanocortin
      1 receptor gene variants. We conclude that numerous melanocortin 1 receptor
      variants predispose to cutaneous melanoma and that possibly the Asp84Glu variant
      confers the highest risk. This predisposition is largely independent of skin type
      and hair color.

PMID- 11511308
TI  - Spl phosphorylation induced by serum stimulates the human alpha2(I) collagen gene
      expression.
AB  - Serum has been known to stimulate collagen production by dermal fibroblasts. As
      part of an ongoing study of the molecular mechanisms of collagen production, we
      have investigated transcriptional regulation of the human alpha2(I) collagen gene
      by serum in human dermal fibroblasts. Serum responsive elements were mapped by
      deletion analysis between bp -353 and -264, and between -148 and -108 in the
      alpha2(I) collagen promoter. Further functional analysis of the alpha2(I)
      collagen promoter containing various substitution mutations revealed that serum
      stimulation of this promoter is mediated equally by a GC-rich region located
      between bp -303 and -271 and by the TCCTCC motif located between bp -123 and 
      128, both of which constitute binding sites for transcription factor Spl and Sp3.
      No differences were observed in electrophoretic mobility shift assays between
      unstimulated and serum stimulated fibroblasts. The Spl inhibitor mithramycin
      blocked stimulation of the alpha2(I) collagen promoter activity by serum.
      Furthermore, immunoprecipitation analysis showed that serum stimulation increased
      Spl phosphorylation. In conclusion, this study characterized response elements
      that mediate serum stimulation of the human alpha2(I) collagen promoter and
      suggests that serum stimulation was mediated via Sp1/Sp3 binding sites in this
      promoter.

PMID- 11511309
TI  - Stress-induced changes in skin barrier function in healthy women.
AB  - Despite clear exacerbation of several skin disorders by stress, the effect of
      psychologic or exertional stress on human skin has not been well studied. We
      investigated the effect of three different stressors, psychologic interview
      stress, sleep deprivation, and exercise, on several dermatologic measures:
      transepidermal water loss, recovery of skin barrier function after tape
      stripping, and stratum corneum water content (skin conductance). We
      simultaneously measured the effects of stress on plasma levels of several stress
      response hormones and cytokines, natural killer cell activity, and absolute
      numbers of peripheral blood leukocytes. Twenty-five women participated in a
      laboratory psychologic interview stress, 11 women participated in one night of
      sleep deprivation, and 10 women participated in a 3 d exercise protocol. The
      interview stress caused a delay in the recovery of skin barrier function, as well
      as increases in plasma cortisol, norepinephrine, interleukin-1beta and
      interleukin-10, tumor necrosis factor-alpha, and an increase in circulating
      natural killer cell activity and natural killer cell number. Sleep deprivation
      also decreased skin barrier function recovery and increased plasma interleukin
      1beta, tumor necrosis factor-alpha, and natural killer cell activity. The
      exercise stress did not affect skin barrier function recovery, but caused an
      increase in natural killer cell activity and circulating numbers of both
      cytolytic T lymphocytes and helper T cells. In addition, cytokine responses to
      the interview stress were inversely correlated with changes in barrier function
      recovery. These results suggest that acute psychosocial and sleep deprivation
      stress disrupts skin barrier function homeostasis in women, and that this
      disruption may be related to stress-induced changes in cytokine secretion.

PMID- 11511310
TI  - Phenotypic characterization of human CD4+ regulatory T cells obtained from
      cutaneous dinitrochlorobenzene-induced delayed type hypersensitivity reactions.
AB  - In this study, we describe the generation and characterization of cloned human
      CD4+ T lymphocyte populations that have infiltrated into cutaneous, 2,4
      dinitrochlorobenzene-induced delayed type hypersensitivity reactions in healthy
      human subjects. It is shown that, in addition to T helper type 1 clones, elevated
      numbers of regulatory T clones, producing high levels of interleukin-10 and
      interleukin-5, but no measurable interleukin-4, were isolated from delayed type
      hypersensitivity reactions in four of six donors. A subsequent challenge with 2,4
      dinitrochlorobenzene of two donors from whom only few interleukin-10-producing T
      cell clones had been generated after primary challenge, resulted in a decrease in
      the frequency of T helper type 1 clones and a strong increase in the number of
      interleukin-10-producing T helper type 2 and regulatory T clones. Culture
      supernatants from the latter cells, activated with anti-CD3 and anti-CD28
      monoclonal antibody, inhibited alloantigen-mediated T cell proliferation which
      was, partly dependent on interleukin-10, and independent of transforming growth
      factor-beta. In addition, dendritic cells generated in vitro in the presence of
      these culture supernatants were impaired in their ability to induce alloantigen
      induced proliferative responses. Differential expression of transcripts for the
      T1/ST2 molecule enabled a phenotypic distinction between resting regulatory T
      cells and T helper type 2 cells, but not between regulatory T cells and T helper
      type 1 cells. This experimental model provides a useful tool to isolate human
      inflammatory and anti-inflammatory T cell subpopulations and, furthermore,
      enables the study of the kinetics of their appearance into delayed type
      hypersensitivity reactions.

PMID- 11511311
TI  - Specific cytotoxic T lymphocyte responses against Melan-A/MART1, tyrosinase and
      gp100 in vitiligo by the use of major histocompatibility complex/peptide
      tetramers: the role of cellular immunity in the etiopathogenesis of vitiligo.
AB  - Vitiligo is a common skin disease characterized by the presence of well
      circumscribed, depigmented, milky white macules devoid of identifiable
      melanocytes. Although the detection of circulating anti-melanocytic antibodies
      and of infiltrating lymphocytes at the margin of lesions supports the view that
      vitiligo is an autoimmune disorder, its etiology remains unknown. In particular,
      it is still a matter of debate whether the primary pathogenic role is exerted by
      humoral or cellular abnormal immune responses. In this study, the presence of
      specific cytotoxic T lymphocyte responses against the melanocyte differentiation
      antigens Melan-A/MART1, tyrosinase, and gp100 in vitiligo patients have been
      investigated by the use of major histocompatibility complex/peptide tetramers.
      High frequencies of circulating melanocyte-specific CD8+ T cells were found in
      all vitiligo patients analyzed. These cells exerted anti-melanocytic cytotoxic
      activity in vitro and expressed skin-homing capacity. In one patient melanocyte
      specific cells were characterized by an exceptionally high avidity for their
      peptide/major histocompatibility complex ligand. These findings strongly suggest
      a role for cellular immunity in the pathogenesis of vitiligo and impact on the
      common mechanisms of self tolerance.

PMID- 11511312
TI  - The Bax/Bcl-2 ratio determines the susceptibility of human melanoma cells to
      CD95/Fas-mediated apoptosis.
AB  - Defective cytochrome c release and the resulting loss of caspase-3 activation was
      recently shown to be essential for the susceptibility of human melanoma cells to
      CD95/Fas-induced apoptosis. Cytochrome c release from mitochondria is regulated
      by the relative amounts of apoptosis-promoting and apoptosis-inhibiting Bcl-2
      proteins in the outer membrane of these organelles. The assignment of Bax/Bcl-2
      ratios by quantitative Western blotting in 11 melanoma cell populations revealed
      a relation to the susceptibility to CD95-mediated apoptosis. We could show that a
      low Bax/Bcl-2 ratio was characteristic for resistant cells and a high Bax/Bcl-2
      ratio was characteristic for sensitive cells. Low Bax expression was not a
      consequence of mutations in the p53 coding sequence. The Bax/Bcl-2 ratio was also
      in clear correlation with sensitivity to another cell death inducer, N
      acetylsphingosine. Furthermore, Bcl-2 overexpression abolished apoptosis
      triggered by both apoptotic stimuli, confirming the critical role of the Bax/Bcl
      2 ratio as a rheostat that determines the susceptibility to apoptosis in melanoma
      cells by regulating mitochondrial function. Interestingly, some chemotherapeutics
      lead to the activation of death pathways by CD95L upregulation, ceramide
      generation, direct activation of upstream caspases, or upregulation of
      proapoptotic genes. Taken together, these signals enter the apoptotic pathway
      upstream of mitochondria, resulting in activation of this central checkpoint. We
      therefore assumed that apoptosis deficiency of malignant melanoma can be
      circumvented by drugs directly influencing mitochondrial functions. For this
      purpose we used betulinic acid, a cytotoxic agent selective for melanoma,
      straightly perturbing mitochondrial functions. In fact, betulinic acid induced
      mitochondrial cytochrome c release and DNA fragmentation in both CD95-resistant
      and CD95-sensitive melanoma cell populations, independent of the Bax/Bcl-2 ratio.

PMID- 11511313
TI  - Keratinocytes play a role in regulating distribution patterns of recipient
      melanosomes in vitro.
AB  - Melanosomes in keratinocytes of Black skin are larger and distributed
      individually whereas those within keratinocytes of Caucasian skin are smaller and
      distributed in clusters. This disparity contributes to differences in skin
      pigmentation and photoprotection, but the control of these innate distribution
      patterns is poorly understood. To investigate this process, cocultures were
      established using melanocytes and keratinocytes derived from different racial
      backgrounds and were examined by electron microscopy. Melanosomes transferred to
      keratinocytes were categorized as individual or in various clusters. Melanosome
      size was also determined for individual and clustered melanosomes. Results
      indicate that, in our model system, melanosomes in keratinocytes from different
      racial backgrounds show a combination of clustered and individual melanosomes.
      When keratinocytes from dark skin were cocultured with melanocytes from (i) dark
      skin or (ii) light skin, however, recipient melanosomes were individual versus
      clustered in (i) 77% vs 23% and (ii) 64% vs 36%, respectively. In contrast, when
      keratinocytes from light skin were cocultured with melanocytes from (iii) dark
      skin or (iv) light skin, recipient melanosomes were individual versus clustered
      in (iii) 34% vs 66% and (iv) 39% vs 61%, respectively. These results indicate
      that recipient melanosomes, regardless of origin, are predominantly distributed
      individually by keratinocytes from dark skin, and in membrane-bound clusters by
      those from light skin. There were also differences in melanosome size from dark
      or light donor melanocytes. Melanosome size was not related to whether the
      melanosomes were distributed individually or clustered, however, in cocultures.
      These results suggest that regulatory factor(s) within the keratinocyte determine
      recipient melanosome distribution patterns.

PMID- 11511314
TI  - Heritability and gene-environment interactions for melanocytic nevus density
      examined in a U.K. adolescent twin study.
AB  - Risk factors for melanoma include environmental (particularly ultraviolet
      exposure) and genetic factors. In rare families, susceptibility to melanoma is
      determined by high penetrance mutations in the genes CDKN2A or CDK4, with more
      common, less penetrant genes also postulated. A further, potent risk factor for
      melanoma is the presence of large numbers of melanocytic nevi so that genes
      controlling nevus phenotype could be such melanoma susceptibility genes. A large
      Australian study involving twins aged 12 y of predominantly U.K. ancestry showed
      strong evidence for genetic influence on nevus number and density. We carried out
      essentially the same study in the U.K. to gain insight into gene-environment
      interactions for nevi. One hundred and three monozygous (MZ) and 118 dizygous
      (DZ) twin pairs aged 10-18 y were examined in Yorkshire and Surrey, U.K. Nevus
      counts were, on average, higher in boys (mean = 98.6) than girls (83.8) (p =
      0.009) and higher in Australia (110.4) than in the U.K. (79.2, adjusted to age 12
      y, p < 0.0001), and nevus densities were higher on sun-exposed sites (92 per m2)
      than sun-protected sites (58 per m2) (p < 0.0001). Correlations in sex and age
      adjusted nevus density were higher in MZ pairs (0.94, 95%CI 0.92-0.96) than in DZ
      pairs (0.61, 95%CI 0.49-0.72), were notably similar to those of the Australian
      study (MZ = 0.94, DZ = 0.60), and were consistent with high heritability (65% in
      the U.K., 68% in Australia). We conclude that emergence of nevi in adolescents is
      under strong genetic control, whereas environmental exposures affect the mean
      number of nevi.

PMID- 11511315
TI  - Regulation of adrenomedullin secretion in cultured human skin and oral
      keratinocytes.
AB  - Adrenomedullin, a potent vasoactive peptide, is actively secreted from primary
      cultures of human oral and skin keratinocytes, but nothing is known of the
      regulation of its release. This study describes the effects of a range of
      substances on adrenomedullin production from cultures of oral and skin
      keratinocytes. We have established that keratinocytes do not store adrenomedullin
      but secrete it constitutively. Cytokines interleukin-1alpha and -1beta, tumor
      necrosis factor-alpha and -beta, and the bacterial product, lipopolysaccharide,
      significantly stimulate adrenomedullin secretion from oral but not skin
      keratinocytes. Both transforming growth factor-beta1 and interferon-gamma are
      potent suppressors of adrenomedullin secretion from both cell types, as are
      forskolin, di-butyryl cyclic adenosine monophosphate, and adrenocorticotropin.
      The peptides thrombin and endothelin-1 increase adrenomedullin production,
      particularly from skin keratinocytes. These findings indicate that there are
      differences in the regulation of adrenomedullin production between oral and skin
      keratinocytes and that oral keratinocytes are particularly responsive to the
      action of inflammatory cytokines. This raises the possibility that adrenomedullin
      may serve a different functions in oral mucosa and skin.

PMID- 11511316
TI  - Selective expression of FLIP in malignant melanocytic skin lesions.
AB  - FLIP (FLICE Inhibitory Protein) is a recently identified intracellular inhibitor
      of caspase-8 activation that potently inhibits cell death mediated by all death
      receptors including Fas and TRAIL. FLIP has recently been shown to favor tumor
      growth and immune escape in mouse tumor models. We analyzed FLIP expression by
      immunohistochemistry in a panel of 61 benign and malignant human melanocytic skin
      lesions. FLIP expression was undetectable in all but one benign melanocytic
      lesion (31/32, 97%). In contrast, FLIP was strongly expressed in most melanomas
      (24/29 = 83%). Overexpression of FLIP by transfection in a Fas- and TRAIL
      sensitive human melanoma cell line rendered this cell line more resistant to
      death mediated by both TRAIL and FasL. Selective expression of FLIP by human
      melanomas may confer in vivo resistance to FasL and TRAIL, thus representing an
      additional mechanism by which melanoma cells escape immune destruction.

PMID- 11511317
TI  - Ultraviolet exposure as the main initiator of p53 mutations in basal cell
      carcinomas from psoralen and ultraviolet A-treated patients with psoriasis.
AB  - Basal cell carcinoma, the most frequent skin cancer in humans, is often linked to
      chronic sun exposure. In psoralen and ultraviolet A-treated psoriatic patients,
      basal cell carcinomas may occur even more frequently; however, the exact etiology
      and mechanisms of tumorigenesis in psoriatic patients are unclear because
      psoralen and ultraviolet A is not only a carcinogen but also an immunosuppressor
      and because psoralen and ultraviolet A-treated psoriatic patients often have
      other (co)carcinogenic risk factors (e.g, therapeutic exposure to ultraviolet B,
      X-ray radiation, arsenic, tar, and/or chemotherapeutic agents such as
      methotrexate). In this study, we analyzed the DNA of 13 basal cell carcinomas
      from five psoralen and ultraviolet A-treated psoriatic patients for mutations of
      the p53 tumor suppressor gene. DNA sequencing revealed a total of 11 mis-sense,
      two non-sense, and four silent mutations in seven of the 13 basal cell carcinomas
      (54%). Of the 13 total mis-sense or non-sense mutations, 12 (92%) occurred at
      dipyrimidine sites and nine (69%) were of the ultraviolet fingerprint type (eight
      C-->T transitions and one CC-->TT transition). Three of the C-->T transitions
      occurred at dipyrimidine sites opposite a 5'-TpG sequence (a potential psoralen
      binding site and target for psoralen and ultraviolet A mutagenesis). Thus,
      whether these mutations were induced by ultraviolet or psoralen and ultraviolet A
      was not clear. In addition, two other mutations (15%) occurred at 5'-TpG sites,
      one (8%) occurred at a 5'-TpA site (the most frequent site of psoralen binding
      and mutagenesis in cell and murine studies), and one (8%) involved a G-->T
      transversion. These results suggest that (i) the major initiator of p53 mutations
      in basal cell carcinoma in psoralen and ultraviolet A-treated psoriasis patients
      is environmental and/or therapeutic ultraviolet(B) exposure, and that (ii)
      psoralen and ultraviolet A itself causes only a smaller portion of p53 mutations
      in psoralen and ultraviolet A-associated basal cell carcinomas.

PMID- 11511318
TI  - Perilesional injection of r-GM-CSF in patients with cutaneous melanoma
      metastases.
AB  - Based on evidence that granulocyte-macrophage colony stimulating factor (GM-CSF)
      induces a potent systemic antitumor immunity, we tested recombinant GM-CSF in
      advanced melanoma. Seven patients with histologically confirmed cutaneous
      melanoma metastases were treated with perilesional intracutaneous injections of
      recombinant GM-CSF and observed for a follow-up time of 5 y. All but two patients
      had a decrease in the total number of metastases. At the end of the 5 y follow-up
      three of the seven patients are still alive with only one patient receiving other
      than surgical therapy, and one patient died tumor free at the age of 93. The
      remaining three patients died from progressive melanoma. Perilesional intradermal
      GM-CSF therapy resulted in a mean survival time of 33 mo. The treatment was well
      tolerated and no side-effects other than local erythema at the injection sites
      and mild drowsiness were seen. Immunohistochemical analysis with staining for
      CD14 and GM-CSF receptor demonstrated an increased infiltration of monocytes into
      both injected and noninjected cutaneous melanoma metastases compared with lesions
      excised prior to the initiation of therapy. The same was true for CD4- and CD8
      positive lymphocytes. This phenomenon, together with GM-CSF-induced leukocyte
      counts of more than 20,000 during therapy, support the possible impact of a
      systemic over a locally induced reaction by GM-CSF. To our knowledge this is the
      first report that intracutaneously injected GM-CSF results in long-lasting
      reduction of melanoma metastases.

PMID- 11511320
TI  - Plasma and skin concentration of 5-methoxypsoralen in psoriatic patients after
      oral administration.
AB  - The aim of this work was to investigate the distribution of 5-methoxypsoralen in
      the skin after oral administration of the drug and to examine the correlation
      between skin and plasma concentrations. 5-Methoxypsoralen skin concentration was
      measured in both healthy and psoriatic sites of 10 psoriatic patients after
      single and multiple oral doses. The results obtained show that 5-methoxypsoralen
      accumulates at higher levels in the more external layers of the skin after oral
      administration. The high affinity of drug for the stratum corneum was confirmed
      by in vitro skin affinity measurements. The concentration of 5-methoxypsoralen in
      the skin was similar in both psoriatic and healthy sites, indicating that the
      pathology does not influence drug distribution in the skin. After single dose
      administration, a linear correlation was found between skin and plasma drug
      concentration. After multiple dose administration, drug concentration in the skin
      was fairly constant despite the variable plasma concentrations in different
      subjects.

PMID- 11511319
TI  - Molecular detection of metastatic melanoma cells in cerebrospinal fluid in
      melanoma patients.
AB  - Melanoma frequently metastasizes to the central nervous system (CNS). The
      diagnosis of CNS metastases typically is made following the onset of clinical
      symptoms. Thus, more sensitive diagnostic approaches are needed to identify
      subclinical CNS metastases. Currently, standard cytologic analysis of the
      cerebrospinal fluid (CSF) is limited by its poor sensitivity. A more sensitive
      assay was therefore developed using multiple reverse transcriptase-polymerase
      chain reaction (RT-PCR) markers. CSF was collected and assessed by RT-PCR for
      three known melanoma-associated markers (MAGE-3, MART-1, and tyrosinase) to
      detect occult metastatic melanoma cells in the CSF of 37 American Joint Committee
      on Cancer (AJCC) stage IV melanoma patients. Cytologic analysis of CSF was
      performed on all patients, and immunohistochemistry (IHC) analysis was performed
      on 33 CSF samples using anti-S100 and anti-HMB-45 antibodies. Only one patient
      (3%) had tumor-positive CSF cytology and IHC upon entry into the study, whereas
      12 patients (32%) were positive for at least one RT-PCR marker. The correlation
      between CSF RT-PCR positivity of MART-1 and/or MAGE-3 and the development of CNS
      metastases at 3 mo was significant (p = 0.04). Fifteen of 37 patients (41%) had
      either positive MRI and/or positive RT-PCR results. Multimarker RT-PCR is more
      informative and sensitive than cytology/IHC in assessing the CSF of melanoma
      patients.

PMID- 11511321
TI  - Lack of genetic and epigenetic changes in CDKN2A in melanocytic nevi.

PMID- 11511322
TI  - Real-time evidence of in vivo leukocyte trafficking in human skin by reflectance
      confocal microscopy.

PMID- 11511323
TI  - Melanosomal pH, pink locus protein and their roles in melanogenesis.

PMID- 11511324
TI  - High-throughput genotyping of single nucleotide polymorphisms with rolling circle
      amplification.
AB  - BACKGROUND: Single nucleotide polymorphisms (SNPs) are the foundation of powerful
      complex trait and pharmacogenomic analyses. The availability of large SNP
      databases, however, has emphasized a need for inexpensive SNP genotyping methods
      of commensurate simplicity, robustness, and scalability. We describe a solution
      based, microtiter plate method for SNP genotyping of human genomic DNA. The
      method is based upon allele discrimination by ligation of open circle probes
      followed by rolling circle amplification of the signal using fluorescent primers.
      Only the probe with a 3' base complementary to the SNP is circularized by
      ligation. RESULTS: SNP scoring by ligation was optimized to a 100,000 fold
      discrimination against probe mismatched to the SNP. The assay was used to
      genotype 10 SNPs from a set of 192 genomic DNA samples in a high-throughput
      format. Assay directly from genomic DNA eliminates the need to preamplify the
      target as done for many other genotyping methods. The sensitivity of the assay
      was demonstrated by genotyping from 1 ng of genomic DNA. We demonstrate that the
      assay can detect a single molecule of the circularized probe. CONCLUSIONS:
      Compatibility with homogeneous formats and the ability to assay small amounts of
      genomic DNA meets the exacting requirements of automated, high-throughput SNP
      scoring.

PMID- 11511325
TI  - Gastroenteritis outbreaks associated with Norwalk-like viruses and their
      investigation by nested RT-PCR.
AB  - BACKGROUND: Norwalk-like viruses are the most common cause of gastroenteritis
      outbreaks and sporadic cases of vomiting and diarrhoea. In healthy individuals
      infection is often mild and short-lived but in debilitated patients infection can
      be severe. It is essential that the virus laboratory can offer a sensitive and
      specific test, delivered in a timely manner. METHODS: We have developed a nested
      reverse transcriptase PCR based on published primers against the RNA polymerase
      gene and after comparison with electronmicroscopy used the assay to investigate
      31 outbreaks of gastroenteritis. These were in diverse situations including
      nursing homes, small district hospitals, large general hospitals, a ferry ship,
      hotels, restaurants and staff canteens. RESULTS: A positive diagnosis was made in
      30/31 outbreaks investigated giving an overall outbreak positive detection rate
      of 97%. At an individual patient level there was a positive diagnostic rate of
      11.5% in a large hospital environment to 100% in smaller outbreak situations. The
      average patient positive rate was 34%. In addition we investigated 532 control
      faecal specimens from adults. Of these 530 were negative and 2 were repeatedly
      positive. CONCLUSIONS: It is essential that insensitive electronmicroscopy is
      replaced with the more sensitive reverse transcription PCR assays. These tests
      should be made available "on call" at weekends and public holidays. It is also
      important that outbreaks of NLV infection are monitored using sensitive RT-PCR
      assays so that the laboratory information can be used in ascertaining the spread
      and duration of the outbreak.

PMID- 11511326
TI  - Long-term resource variation and group size: a large-sample field test of the
      Resource Dispersion Hypothesis.
AB  - BACKGROUND: The Resource Dispersion Hypothesis (RDH) proposes a mechanism for the
      passive formation of social groups where resources are dispersed, even in the
      absence of any benefits of group living per se. Despite supportive modelling, it
      lacks empirical testing. The RDH predicts that, rather than Territory Size (TS)
      increasing monotonically with Group Size (GS) to account for increasing metabolic
      needs, TS is constrained by the dispersion of resource patches, whereas GS is
      independently limited by their richness. We conducted multiple-year tests of
      these predictions using data from the long-term study of badgers Meles meles in
      Wytham Woods, England. The study has long failed to identify direct benefits from
      group living and, consequently, alternative explanations for their large group
      sizes have been sought. RESULTS: TS was not consistently related to resource
      dispersion, nor was GS consistently related to resource richness. Results
      differed according to data groupings and whether territories were mapped using
      minimum convex polygons or traditional methods. Habitats differed significantly
      in resource availability, but there was also evidence that food resources may be
      spatially aggregated within habitat types as well as between them. CONCLUSIONS:
      This is, we believe, the largest ever test of the RDH and builds on the long-term
      project that initiated part of the thinking behind the hypothesis. Support for
      predictions were mixed and depended on year and the method used to map territory
      borders. We suggest that within-habitat patchiness, as well as model assumptions,
      should be further investigated for improved tests of the RDH in the future.

PMID- 11511327
TI  - Assessing the knowledge of bronchial asthma among primary health care physicians
      in Crete: a pre- and post-test following an educational course.
AB  - AIM: To assess the level of knowledge for bronchial asthma of the primary
      healthcare physicians serving a rural population on the island of Crete, both
      before and immediately after a one-day educational course. METHODS: Twenty-one
      primary health care physicians, randomly selected from a list of 14 Health Care
      Centres on the island of Crete were invited to participate in the study and
      attended an educational course. Nine of the 21 physicians were fully qualified
      general practitioners, while the remainder were non-specialized (NSs) physicians
      who had recently graduated from the University of Crete, Medical School. A
      questionnaire of 20 items based on current bronchial asthma clinical guidelines
      was used. Three scores, the mean total, knowledge subscore and attitudes
      subscore, were calculated for each group of physicians, both before and after the
      course. RESULTS: At baseline mean total score and knowledge and attitudes
      subscores were higher for non-specialized physicians than for the general
      practitioners, but the differences were not statistically significant (p > 0.05).
      The knowledge subscore was improved in both groups, however the difference was
      statistically significant only for the non-specialized physicians (t = 2.628,
      d.f. = 11, p < 0.05). The mean total score after the course was significantly
      higher for the non-specialized physicians in comparison to that of the general
      practitioners (t=-2.688, d.f. = 19, p < 0.05). CONCLUSIONS: This study adds to
      the information about the success of continuing medical education, and also
      demonstrates that the recent graduates in the studied population, could be
      educated with more positive results than the fully qualified practitioners

PMID- 11511329
TI  - Evaluating our end-of-life practice.
AB  - Ferrand et al's recent study of withholding and withdrawing life support in
      intensive care units in France reminds us that reporting end-of-life practices is
      an important step towards enhancing end-of-life care. The study highlights
      differences between the paternalistic approach to decision making in Europe, and
      the patient autonomy model in the USA. However, the reasons intensivists report
      for withholding or withdrawing life support are similar in both cultures.
      Intensivists in France make decisions despite a lack of formal guidelines in
      their country. This study should serve as a stimulus for educating the public and
      motivating more groups to monitor their end-of-life practices.

PMID- 11511328
TI  - Helium oxygen mixtures in the intensive care unit.
AB  - Heliox, a mixture of helium and oxygen, has a density that is less than that of
      air. Breathing heliox leads to a reduction in resistance to flow within the
      airways, and consequently to a decrease in the work of breathing (WOB),
      particularly in disorders that are characterized by increased airways resistance.
      Beneficial effects have been observed in patients with asthma, chronic
      obstructive pulmonary disease (COPD), bronchiolitis, bronchopulmonary dysplasia
      and upper airways obstruction. Until we have conclusive data that attest to the
      efficacy of heliox in such conditions, its use will remain controversial.
      Meanwhile, it appears wise not to incorporate heliox therapy into routine
      practice because of technical complications and high costs.

PMID- 11511330
TI  - Alarms in the intensive care unit: how can the number of false alarms be reduced?
AB  - Many alarms, as they now exist in most monitoring systems, are not usually
      perceived as helpful by the medical staff because of the high incidence of false
      alarms. This paper gives an overview of the problems related to their current
      design and the objectives of monitoring. The current approaches used to improve
      the situation are then presented from two main standpoints: organizational and
      behavioural on the one hand, and technical on the other.

PMID- 11511331
TI  - Optimizing antibiotic therapy in the intensive care unit setting.
AB  - Antibiotics are one of the most common therapies administered in the intensive
      care unit setting. In addition to treating infections, antibiotic use contributes
      to the emergence of resistance among pathogenic microorganisms. Therefore,
      avoiding unnecessary antibiotic use and optimizing the administration of
      antimicrobial agents will help to improve patient outcomes while minimizing
      further pressures for resistance. This review will present several strategies
      aimed at achieving optimal use of antimicrobial agents. It is important to note
      that each intensive care unit should have a program in place which monitors
      antibiotic utilization and its effectiveness. Only in this way can the impact of
      interventions aimed at improving antibiotic use (e.g. antibiotic rotation, de
      escalation therapy) be evaluated at the local level.

PMID- 11511332
TI  - Overdistension in ventilated children.
AB  - Ventilating patients with acute respiratory failure according to standardized
      recommendations can lead to varying volume-pressure (V-P) relationships and
      overdistension. Young children may be more susceptible than adults to
      overdistension, and individual evaluation of the effects of ventilator settings
      is therefore required. Three studies have applied indices for the detection of
      overdistension to dynamic V-P curves in ventilated children. Two of those studies
      compared these indices to those obtained using a reference technique ([quasi]
      static V-P curves), and suggested that the c coefficient of a second order
      polynomial equation (SOPE) and the ratio of the volume-dependent elastance to
      total dynamic elastance (%E2) were suitable indices for estimating
      overdistension.

PMID- 11511333
TI  - The 26th Congress of the Scandinavian Society of Anaesthesiology and Intensive
      Care Medicine, Tromso, Norway, 13-17 June 2001.
AB  - The 26th Congress of the Scandinavian Society of Anaesthesiology and Intensive
      Care Medicine took place in the state-of-the art Tromso University Hospital.
      There were over 500 participants, and approximately 300 oral and poster
      presentations highlighted the latest progress in diverse areas. Much interest
      focused on activated protein C (APC) and other ways forward in sepsis treatment,
      pain management, novel markers of neurotrauma and antioxidants in bypass surgery.
      The meeting continues to be the leading anaesthesiology and intensive care
      conference in the region.

PMID- 11511334
TI  - Intensive care management of organophosphate insecticide poisoning.
AB  - INTRODUCTION: Organophosphate (OP) insecticides inhibit both cholinesterase and
      pseudo-cholinesterase activities. The inhibition of acetylcholinesterase causes
      accumulation of acetylcholine at synapses, and overstimulation of
      neurotransmission occurs as a result of this accumulation. The mortality rate of
      OP poisoning is high. Early diagnosis and appropriate treatment is often life
      saving. Treatment of OP poisoning consists of intravenous atropine and oximes.
      The clinical course of OP poisoning may be quite severe and may need intensive
      care management. We report our experience with the intensive care management of
      serious OP insecticide poisonings. METHODS: A retrospective study was performed
      on the patients with OP poisoning followed at our medical intensive care unit.
      Forty-seven patients were included. Diagnosis was performed from the history
      taken either from the patient or from the patient's relatives about the agent
      involved in the exposure. Diagnosis could not be confirmed with serum and red
      blood cell anticholinesterase levels because these are not performed at our
      institution. Intravenous atropine and pralidoxime was administered as soon as
      possible. Pralidoxime could not be given to 16 patients: 2 patients did not
      receive pralidoxime because they were late admissions and 14 did not receive
      pralidoxime because the Ministry of Health office was out of stock. Other
      measures for the treatment were gastric lavage and administration of activated
      charcoal via nasogastric tube, and cleansing the patient's body with soap and
      water. The patients were intubated and mechanically ventilated if the patients
      had respiratory failure, a depressed level of consciousness, which causes an
      inability to protect the airway, and hemodynamic instability. Mechanical
      ventilation was performed as synchronized intermittent mandatory ventilation +
      pressure support mode, either as volume or pressure control. Positive end
      expiratory pressure was titrated to keep SaO2 above 94% with 40% FIO2. Weaning
      was performed using either T-tube trials or pressure support weaning. The chi
      square test was used for statistical analysis. Data are presented as mean +/-
      standard deviation. RESULTS: There were 25 female and 22 male patients. Thirty
      two (68%) were suicide attempts and 15 (32%) were accidental exposure. The
      gastrointestinal route was the main route in 44 (93.6%) patients. The mortality
      rates for the patients who did and did not receive pralidoxime were 32 and 18.7%,
      respectively, and were not statistically different. The most frequent signs were
      meiosis, change in mental status, hypersalivation and fasciculations. Ten
      patients (21.2%) required mechanical ventilation. The mortality rate for the
      patients who required mechanical ventilation was 50%, but the rate was 21.6% for
      the patients who were not mechanically ventilated. Intermediate syndrome was
      observed in 9 (19.1%) patients. Complications were observed in 35 (74.4%)
      patients. These complications were respiratory failure (14 patients), aspiration
      pneumonia (10 patients), urinary system infection (6 patients), convulsion (4
      patients) and septic shock (1 patient). The duration of the intensive care stay
      was 5.2 +/- 3.0 days. DISCUSSION: Ingestion of OP compounds for suicidal purposes
      is a major problem, especially in developing countries. Thirty-two (68%) of our
      patients used the OP insecticide for suicide. Two patients did not receive
      pralidoxime because of delayed admission and they were successfully treated with
      atropine alone. Three of the patients who did not receive pralidoxime because of
      unavailability died. The mortality rate was no different between the patients
      treated with pralidoxime or those without pralidoxime. De Silva and coworkers
      have also reported that the mortality rate was not different between each group.
      Three patients with intermediate syndrome died due to delay for endotracheal
      intubation. The average respiratory rate of these patients increased from 22 to
      38 breaths/min, which is an important sign of respiratory distress. The nurse to
      patient ratio was increased after these events. Early recognition of respiratory
      failure resulting in intubation and mechanical ventilation is a life-saving
      intervention for patients with OP poisoning. Respiratory failure is the most
      troublesome complication, which was observed in 35 (74.4%) patients. Patients
      with OP poisoning may have respiratory failure for many reasons, including
      aspiration of the gastric content, excessive secretions, pneumonia and septicemia
      complicating acute respiratory distress syndrome. CONCLUSIONS: OP insecticide
      poisoning is a serious condition that needs rapid diagnosis and treatment. Since
      respiratory failure is the major reason for mortality, careful monitoring,
      appropriate management and early recognition of this complication may decrease
      the mortality rate among these patients.

PMID- 11511335
TI  - Enteral feeding in the critically ill: comparison between the supine and prone
      positions: a prospective crossover study in mechanically ventilated patients.
AB  - INTRODUCTION: Prone position is effective in mechanically ventilated patients to
      improve oxygenation. It is unknown if prone position affects gastric emptying and
      the ability of continued enteral feeding. AIM: To determine tolerance of enteral
      feeding by measuring gastric residual volumes in enterally fed patients during
      supine and prone positions. METHODS: Consecutive mechanically ventilated
      intensive care patients who were turned to prone position were included. All
      patients were studied for 6 hours in supine position, immediately followed by 6
      hours in prone position, or vice versa. The rate of feeding was unchanged during
      the study period. Gastric residual volume was measured by suctioning the naso
      gastric tube after 3 and 6 hours in the same position. Wilcoxon test and
      regression analysis were used for analysis. RESULTS: The median volume of
      administered enteral feeds was 95 ml after 6 hours in supine position and 110 ml
      after 6 hours in prone position (P = 0.85). In 10 patients, a greater gastric
      residual volume was found in prone position. In eight others a greater volume was
      found in supine position. In 18 of 19 patients, gastric residual volumes in both
      positions were > or = 150 ml in 6 hours or < or = 150 ml in 6 hours.
      Significantly more sedatives were used in prone position. Regression analysis
      excluded dopamine dose and the starting position as confounders. CONCLUSION: Our
      results suggest that enteral feeding can be continued when a patient is turned
      from supine to prone position or vice versa. The results indicate that patients
      with a clinically significant gastric residual volume in one position are likely
      to have a clinically significant gastric residual volume in the other position.

PMID- 11511336
TI  - Airway pressure release ventilation increases cardiac performance in patients
      with acute lung injury/adult respiratory distress syndrome.
AB  - BACKGROUND: The purpose of the present study is to determine whether airway
      pressure release ventilation (APRV) can safely enhance hemodynamics in patients
      with acute lung injury (ALI) and/or adult respiratory distress syndrome (ARDS),
      relative to pressure control ventilation (PCV). METHODS: Patients with severe
      acute lung injury or ARDS who were managed with inverse-ratio pressure control
      ventilation, neuromuscular blockade and a pulmonary artery catheter were switched
      to APRV. Hemodynamic performance, as well as pressor and sedative needs, was
      assessed after discontinuing neuromuscular blockade RESULTS: Mean age was 58 +/-
      9 years (n = 12) and mean Lung Injury Score was 7.6 +/- 2.1. Temperature and
      arterial oxygen tension/fractional inspired oxygen (FiO2) were similar among the
      patients. Peak airway pressures fell from 38 +/- 3 for PCV to 25 +/- 3 cmH2O for
      APRV, and mean pressures fell from 18 +/- 3 for PCV to 12 +/- 2 cmH2O for APRV.
      Paralytic use and sedative use were significantly lower with APRV than with PCV.
      Pressor use decreased substantially with ARPV. Lactate levels remained normal,
      but decreased on APRV. Cardiac index rose from 3.2 +/- 0.4 for PCV to 4.6 +/- 0.3
      l/min per m2 body surface area (BSA) for APRV, whereas oxygen delivery increased
      from 997 +/- 108 for PCV to 1409 +/- 146 ml/min for APRV, and central venous
      pressure declined from 18 +/- 4 for PCV to 12 +/- 4 cmH2O for APRV. Urine output
      increased from 0.83 +/- 0.1 for PCV to 0.96 +/- 0.12 ml/kg per hour for APRV.
      CONCLUSION: APRV may be used safely in patients with ALI/ARDS, and decreases the
      need for paralysis and sedation as compared with PCV-inverse ratio ventilation
      (IRV). APRV increases cardiac performance, with decreased pressor use and
      decreased airway pressure, in patients with ALI/ARDS.

PMID- 11511337
TI  - Handheld computers in critical care.
AB  - BACKGROUND: Computing technology has the potential to improve health care
      management but is often underutilized. Handheld computers are versatile and
      relatively inexpensive, bringing the benefits of computers to the bedside. We
      evaluated the role of this technology for managing patient data and accessing
      medical reference information, in an academic intensive-care unit (ICU). METHODS:
      Palm III series handheld devices were given to the ICU team, each installed with
      medical reference information, schedules, and contact numbers. Users underwent a
      1-hour training session introducing the hardware and software. Various patient
      data management applications were assessed during the study period. Qualitative
      assessment of the benefits, drawbacks, and suggestions was performed by an
      independent company, using focus groups. An objective comparison between a paper
      and electronic handheld textbook was achieved using clinical scenario tests.
      RESULTS: During the 6-month study period, the 20 physicians and 6 paramedical
      staff who used the handheld devices found them convenient and functional but
      suggested more comprehensive training and improved search facilities. Comparison
      of the handheld computer with the conventional paper text revealed equivalence.
      Access to computerized patient information improved communication, particularly
      with regard to long-stay patients, but changes to the software and the process
      were suggested. CONCLUSIONS: The introduction of this technology was well
      received despite differences in users' familiarity with the devices. Handheld
      computers have potential in the ICU, but systems need to be developed
      specifically for the critical-care environment.

PMID- 11511338
TI  - Capgras syndrome: a clinical manifestation of watershed cerebral infarct
      complicating the use of extracorporeal membrane oxygenation.
AB  - Ischaemic cerebral accidents are frequent following extracorporeal membrane
      oxygenation (ECMO), especially after fixing the reinjection cannula in the right
      primitive carotid artery, which leads to an interruption in downstream flow. We
      describe a rare and unusual symptom of cerebral ischaemic accident that is known
      as Capgras syndrome. This feature is interesting because it may be documented by
      computed tomography (CT) scan and particular electroencephalography signals. It
      appears that our observation represents the first documented case of Capgras
      syndrome complicating ECMO. This incident emphasizes the potential hazards
      associated with right common artery ligature for venoarterial extracorporeal
      membrane oxygenation (VAECMO). In addition, it shows that this psychiatric
      symptom (that has been interpreted psychodynamically for many years) can have an
      organic basis, which should be studied.

PMID- 11511339
TI  - A vicious cycle: RNA silencing and DNA methylation in plants.

PMID- 11511340
TI  - Patterning the embryonic axis: FGF signaling and how vertebrate embryos measure
      time.

PMID- 11511341
TI  - The making and breaking of sister chromatid cohesion.

PMID- 11511342
TI  - Circadian clocks: running on redox.

PMID- 11511343
TI  - Ubiquitin-dependent sorting into the multivesicular body pathway requires the
      function of a conserved endosomal protein sorting complex, ESCRT-I.
AB  - The multivesicular body (MVB) pathway is responsible for both the biosynthetic
      delivery of lysosomal hydrolases and the downregulation of numerous activated
      cell surface receptors which are degraded in the lysosome. We demonstrate that
      ubiquitination serves as a signal for sorting into the MVB pathway. In addition,
      we characterize a 350 kDa complex, ESCRT-I (composed of Vps23, Vps28, and Vps37),
      that recognizes ubiquitinated MVB cargo and whose function is required for
      sorting into MVB vesicles. This recognition event depends on a conserved UBC-like
      domain in Vps23. We propose that ESCRT-I represents a conserved component of the
      endosomal sorting machinery that functions in both yeast and mammalian cells to
      couple ubiquitin modification to protein sorting and receptor downregulation in
      the MVB pathway.

PMID- 11511344
TI  - Plasma membrane repair is mediated by Ca(2+)-regulated exocytosis of lysosomes.
AB  - Plasma membrane wounds are repaired by a mechanism involving Ca(2+)-regulated
      exocytosis. Elevation in intracellular [Ca(2+)] triggers fusion of lysosomes with
      the plasma membrane, a process regulated by the lysosomal synaptotagmin isoform
      Syt VII. Here, we show that Ca(2+)-regulated exocytosis of lysosomes is required
      for the repair of plasma membrane disruptions. Lysosomal exocytosis and membrane
      resealing are inhibited by the recombinant Syt VII C(2)A domain or anti-Syt VII
      C(2)A antibodies, or by antibodies against the cytosolic domain of Lamp-1, which
      specifically aggregate lysosomes. We further demonstrate that lysosomal
      exocytosis mediates the resealing of primary skin fibroblasts wounded during the
      contraction of collagen matrices. These findings reveal a fundamental, novel role
      for lysosomes: as Ca(2+)-regulated exocytic compartments responsible for plasma
      membrane repair.

PMID- 11511345
TI  - Prions affect the appearance of other prions: the story of [PIN(+)].
AB  - Prions are self-propagating protein conformations. Recent research brought
      insight into prion propagation, but how they first appear is unknown. We
      previously established that the yeast non-Mendelian trait [PIN(+)] is required
      for the de novo appearance of the [PSI(+)] prion. Here, we show that the presence
      of prions formed by Rnq1 or Ure2 is sufficient to make cells [PIN(+)]. Thus,
      [PIN(+)] can be caused by more than one prion. Furthermore, an unbiased
      functional screen for [PIN(+)] prions uncovered the known prion gene, URE2, the
      proposed prion gene, NEW1, and nine novel candidate prion genes all carrying
      prion domains. Importantly, the de novo appearance of Rnq1::GFP prion aggregates
      also requires the presence of other prions, suggesting the existence of a general
      mechanism by which the appearance of prions is enhanced by heterologous prion
      aggregates.

PMID- 11511346
TI  - Multiple Gln/Asn-rich prion domains confer susceptibility to induction of the
      yeast [PSI(+)] prion.
AB  - The yeast prion [PSI(+)] results from self-propagating aggregates of Sup35p. De
      novo formation of [PSI(+)] requires an additional non-Mendelian trait, thought to
      result from a prion form of one or more unknown proteins. We find that the
      Gln/Asn-rich prion domains of two proteins, New1p and Rnq1p, can control
      susceptibility to [PSI(+)] induction as well as enhance aggregation of a human
      glutamine expansion disease protein. [PSI(+)] inducibility results from gain-of
      function properties of New1p and Rnq1p aggregates rather than from inactivation
      of the normal proteins. These studies suggest a molecular basis for the
      epigenetic control of [PSI(+)] inducibility and may reveal a broader role for
      this phenomenon in the physiology of protein aggregation.

PMID- 11511347
TI  - Molecular analysis of kinetochore-microtubule attachment in budding yeast.
AB  - The complex series of movements that mediates chromosome segregation during
      mitosis is dependent on the attachment of microtubules to kinetochores, DNA
      protein complexes that assemble on centromeric DNA. We describe the use of live
      cell imaging and chromatin immunoprecipitation in S. cerevisiae to identify ten
      kinetochore subunits, among which are yeast homologs of microtubule binding
      proteins in animal cells. By analyzing conditional mutations in several of these
      proteins, we show that they are required for the imposition of tension on paired
      sister kinetochores and for correct chromosome movement. The proteins include
      both molecular motors and microtubule associated proteins (MAPs), implying that
      motors and MAPs function together in binding chromosomes to spindle microtubules.

PMID- 11511348
TI  - Localized and transient transcription of Hox genes suggests a link between
      patterning and the segmentation clock.
AB  - During development, Hox gene transcription is activated in presomitic mesoderm
      with a time sequence that follows the order of the genes along the chromosome.
      Here, we show that Hoxd1 and other Hox genes display dynamic stripes of
      expression within presomitic mesoderm. The underlying transcriptional bursts may
      reflect the mechanism that coordinates Hox gene activation with somitogenesis.
      This mechanism appears to depend upon Notch signaling, as mice deficient for
      RBPJk, the effector of the Notch pathway, showed severely reduced Hoxd gene
      expression in presomitic mesoderm. These results suggest a molecular link between
      Hox gene activation and the segmentation clock. Such a linkage would efficiently
      keep in phase the production of novel segments with their morphological
      specification.

PMID- 11511349
TI  - FGF signaling controls somite boundary position and regulates segmentation clock
      control of spatiotemporal Hox gene activation.
AB  - Vertebrate segmentation requires a molecular oscillator, the segmentation clock,
      acting in presomitic mesoderm (PSM) cells to set the pace at which segmental
      boundaries are laid down. However, the signals that position each boundary remain
      unclear. Here, we report that FGF8 which is expressed in the posterior PSM,
      generates a moving wavefront at which level both segment boundary position and
      axial identity become determined. Furthermore, by manipulating boundary position
      in the chick embryo, we show that Hox gene expression is maintained in the
      appropriately numbered somite rather than at an absolute axial position. These
      results implicate FGF8 in ensuring tight coordination of the segmentation process
      and spatiotemporal Hox gene activation.

PMID- 11511350
TI  - The path of messenger RNA through the ribosome.
AB  - Using X-ray crystallography, we have directly observed the path of mRNA in the
      70S ribosome in Fourier difference maps at 7 A resolution. About 30 nucleotides
      of the mRNA are wrapped in a groove that encircles the neck of the 30S subunit.
      The Shine-Dalgarno helix is bound in a large cleft between the head and the back
      of the platform. At the interface, only about eight nucleotides (-1 to +7),
      centered on the junction between the A and P codons, are exposed, and bond almost
      exclusively to 16S rRNA. The mRNA enters the ribosome around position +13 to +15,
      the location of downstream pseudoknots that stimulate -1 translational frame
      shifting.

PMID- 11511351
TI  - Allosteric binding of nucleoside triphosphates to RNA polymerase regulates
      transcription elongation.
AB  - The regulation of transcription elongation and termination appears to be governed
      by the ability of RNA polymerase elongation complexes to adopt multiple
      conformational states; however, the factors controlling the distribution between
      these states remain elusive. We used transient-state kinetics to investigate the
      incorporation of single nucleotides. We demonstrate that E. coli RNA polymerase
      contains an allosteric binding site in addition to the catalytic site. Binding of
      the templated nucleoside triphosphate (NTP), but not nontemplated NTPs, to this
      site increases the rate of nucleotide incorporation. The data suggest that RNA
      polymerase can exist in a state that catalyzes synthesis slowly (unactivated) and
      one that catalyzes synthesis rapidly (activated), with the transition from the
      slow to the fast state being induced by binding of the templated NTP to the
      allosteric site.

PMID- 11511353
TI  - Myocardin. a novel potentiator of SRF-mediated transcription in cardiac muscle.
AB  - In the June 29, 2001, issue of Cell, Wang et al. report the discovery of
      myocardin, a cardiac and smooth muscle-specific accessory factor for SRF. This
      work provides insight into the mechanism of cardiac-specific transcription and
      suggests the importance of myocardin in early cardiac development.

PMID- 11511354
TI  - A first step toward understanding membrane fusion induced by herpes simplex
      virus.
AB  - In this issue of Molecular Cell, Carfi et al. present the X-ray structure of the
      N-terminal domains of HveA, a TNF receptor family member, in complex with herpes
      simplex virus gD, providing a first step to understanding the herpesvirus mode of
      membrane fusion.

PMID- 11511355
TI  - The importance of being cleaved: an essential step in killing by enzymatic
      colicins.
AB  - In this issue, de Zamaroczy et al. show that cleavage of the bacterial toxin
      colicin D is required for its ability to kill cells. Surprisingly, the cleavage
      requires the inner membrane peptidase LepB that normally functions in protein
      secretion.

PMID- 11511356
TI  - Mediator, not holoenzyme, is directly recruited to the heat shock promoter by HSF
      upon heat shock.
AB  - Activators of RNA polymerase II (Pol II) transcription have been shown to bind
      several coactivators and basal factors in vitro. Whether such interactions play a
      primary regulatory role in recruiting these factors to activator-associated
      chromosomal target sites in living cells remains unclear. Here, we show that upon
      heat shock the Pol II-free form of Mediator is rapidly recruited to HSF binding
      sites. Unlike the TAFs and Pol II, the interaction between Mediator and HSF on
      chromosomal loci is direct and mechanistically separable from the preinitiation
      complex assembly step. Therefore, the activator-Mediator interaction likely
      underlies the initiation of signal transfer from enhancer-bound activators to the
      basal transcription machinery.

PMID- 11511357
TI  - Binding of the initiation factor sigma(70) to core RNA polymerase is a multistep
      process.
AB  - The interaction of RNA polymerase and its initiation factors is central to the
      process of transcription initiation. To dissect the role of this interface, we
      undertook the identification of the contact sites between RNA polymerase and
      sigma(70), the Escherichia coli initiation factor. We identified nine
      mutationally verified interaction sites between sigma(70) and specific domains of
      RNA polymerase and provide evidence that sigma(70) and RNA polymerase interact in
      at least a two-step process. We propose that a cycle of changes in the interface
      of sigma(70) with core RNA polymerase is associated with progression through the
      process of transcription initiation.

PMID- 11511358
TI  - Precursor RNAs harboring nonsense codons accumulate near the site of
      transcription.
AB  - Messenger RNAs containing premature termination codons (PTCs) are selectively
      eliminated by nonsense-mediated mRNA decay (NMD). Paradoxically, although
      cytoplasmic ribosomes are the only known species capable of PTC recognition, in
      mammals many PTC-containing mRNAs are apparently eliminated prior to release from
      the nucleus. To determine whether PTCs can influence events within the nucleus
      proper, we studied the immunoglobulin (Ig)-mu and T cell receptor (TCR)-beta
      genes using fluorescent in situ hybridization (FISH). Alleles containing PTCs,
      but not those containing a missense mutation or a frameshift followed by frame
      correcting mutations, exhibited elevated levels of pre-mRNA, which accumulated at
      or near the site of transcription. Our data indicate that mRNA reading frame can
      influence events at or near the site of gene transcription.

PMID- 11511360
TI  - Transcriptional regulation by p53 through intrinsic DNA/chromatin binding and
      site-directed cofactor recruitment.
AB  - The tumor suppressor protein, p53, plays a critical role in mediating cellular
      response to stress signals by regulating genes involved in cell cycle arrest and
      apoptosis. p53 is believed to be inactive for DNA binding unless its C terminus
      is modified or structurally altered. We show that unmodified p53 actively binds
      to two sites at -1.4 and -2.3 kb within the chromatin-assembled p21 promoter and
      requires the C terminus and the histone acetyltransferase, p300, for
      transcription. Acetylation of the C terminus by p300 is not necessary for binding
      or promoter activation. Instead, p300 acetylates p53-bound nucleosomes in the p21
      promoter with spreading to the TATA box. Thus, p53 is an active DNA and chromatin
      binding protein that may selectively regulate its target genes by recruitment of
      specific cofactors to structurally distinct binding sites.

PMID- 11511359
TI  - Net1 stimulates RNA polymerase I transcription and regulates nucleolar structure
      independently of controlling mitotic exit.
AB  - The budding yeast RENT complex, consisting of at least three proteins (Net1,
      Cdc14, Sir2), is anchored to the nucleolus by Net1. RENT controls mitotic exit,
      nucleolar silencing, and nucleolar localization of Nop1. Here, we report two new
      functions of Net1. First, Net1 directly binds Pol I and stimulates rRNA synthesis
      both in vitro and in vivo. Second, Net1 modulates nucleolar structure by
      regulating rDNA morphology and proper localization of multiple nucleolar
      antigens, including Pol I. Importantly, we show that the nucleolar and previously
      described cell cycle functions of the RENT complex can be uncoupled by a dominant
      mutant allele of CDC14. The independent functions of Net1 link a key event in the
      cell cycle to nucleolar processes that are fundamental to cell growth.

PMID- 11511361
TI  - A TPR motif cofactor contributes to p300 activity in the p53 response.
AB  - The transcription of p53 target genes involves p300/CBP coactivators, which are
      multiprotein complexes that interact with the p53 activation domain. We report a
      cofactor in the p300 coactivator complex, Strap, which has an unusual structure,
      being composed almost entirely of a tandem series of six tetratricopeptide repeat
      (TPR) motifs. The TPR motif functions as a protein interaction domain, and it is
      consistent with this property that Strap harbors distinct and dedicated domains
      that allow it to bind and augment the interaction between different components of
      the p300 complex. Strap facilitates p53 activity in response to stress, in part
      through the stress-responsive accumulation of Strap protein and interfering with
      the MDM2-dependent downregulation of p53.

PMID- 11511362
TI  - p53DINP1, a p53-inducible gene, regulates p53-dependent apoptosis.
AB  - Using the differential display method combined with a cell line that carries a
      well-controlled expression system for wild-type p53, we isolated a p53-inducible
      gene, termed p53DINP1 (p53-dependent damage-inducible nuclear protein 1). Cell
      death induced by DNA double-strand breaks (DSBs), as well as Ser46
      phosphorylation of p53 and induction of p53AIP1, were blocked when we inhibited
      expression of p53DINP1 by means of an antisense oligonucleotide. Overexpression
      of p53DINP1 and DNA damage by DSBs synergistically enhanced Ser46 phosphorylation
      of p53, induction of p53AIP1 expression, and apoptotic cell death. Furthermore,
      the protein complex interacting with p53DINP1 was shown to phosphorylate Ser46 of
      p53. Our results suggest that p53DINP1 may regulate p53-dependent apoptosis
      through phosphorylation of p53 at Ser46, serving as a cofactor for the putative
      p53-Ser46 kinase.

PMID- 11511363
TI  - Structural analysis of a functional DIAP1 fragment bound to grim and hid
      peptides.
AB  - The inhibitor of apoptosis protein DIAP1 suppresses apoptosis in Drosophila, with
      the second BIR domain (BIR2) playing an important role. Three proteins, Hid,
      Grim, and Reaper, promote apoptosis, in part by binding to DIAP1 through their
      conserved N-terminal sequences. The crystal structures of DIAP1-BIR2 by itself
      and in complex with the N-terminal peptides from Hid and Grim reveal that these
      peptides bind a surface groove on DIAP1, with the first four amino acids
      mimicking the binding of the Smac tetrapeptide to XIAP. The next 3 residues also
      contribute to binding through hydrophobic interactions. Interestingly, peptide
      binding induces the formation of an additional alpha helix in DIAP1. Our study
      reveals the structural conservation and diversity necessary for the binding of
      IAPs by the Drosophila Hid/Grim/Reaper and the mammalian Smac proteins.

PMID- 11511364
TI  - Myc requires distinct E2F activities to induce S phase and apoptosis.
AB  - Previous work has shown that the Myc transcription factor induces transcription
      of the E2F1, E2F2, and E2F3 genes. Using primary mouse embryo fibroblasts deleted
      for individual E2F genes, we now show that Myc-induced S phase and apoptosis
      requires distinct E2F activities. The ability of Myc to induce S phase is
      impaired in the absence of either E2F2 or E2F3 but not E2F1 or E2F4. In contrast,
      the ability of Myc to induce apoptosis is markedly reduced in cells deleted for
      E2F1 but not E2F2 or E2F3. From this data, we propose that the induction of
      specific E2F activities is an essential component in the Myc pathways that
      control cell proliferation and cell fate decisions.

PMID- 11511365
TI  - Integrin-specific activation of Rac controls progression through the G(1) phase
      of the cell cycle.
AB  - Adhesion to fibronectin through the alpha5beta1 integrin enables endothelial
      cells to proliferate in response to growth factors, whereas adhesion to laminin
      through alpha2beta1 results in growth arrest under the same conditions. On
      laminin, endothelial cells fail to translate Cyclin D1 mRNA and activate CDK4 and
      CDK6. Activated Rac, but not MEK1, PI-3K, or Akt, rescues biosynthesis of cyclin
      D1 and progression through the G(1) phase. Conversely, dominant negative Rac
      prevents these events on fibronectin. Mitogens promote activation of Rac on
      fibronectin but not laminin. This process is mediated by SOS and PI-3K and
      requires coordinate upstream signals through Shc and FAK. These results indicate
      that Rac is a crucial mediator of the integrin-specific control of cell cycle in
      endothelial cells.

PMID- 11511366
TI  - Budding yeast Rad9 is an ATP-dependent Rad53 activating machine.
AB  - We find budding yeast Rad9 in two distinct, large, and soluble complexes in cell
      extracts. The larger (> or =850 kDa) complex, found in nondamaged cells, contains
      hypophosphorylated Rad9, whereas the smaller (560 kDa) complex, which forms after
      DNA damage, contains hyperphosphorylated Rad9 and Rad53. This smaller Rad9
      complex is capable of catalyzing phosphorylation and release of active Rad53
      kinase, a process requiring the kinase activity of Rad53. However, Mec1 and Tel1
      are no longer required once the 560 kDa complex has been formed. We propose a
      model whereby Mec1/Tel1-dependent hyperphosphorylation of Rad9 results in
      formation of the smaller Rad9 complex and recruitment of Rad53. This complex then
      catalyzes activation of Rad53 by acting as a scaffold that brings Rad53 molecules
      into close proximity, facilitating Rad53 in trans autophosphorylation and
      subsequent release of activated Rad53.

PMID- 11511367
TI  - Mre11 protein complex prevents double-strand break accumulation during
      chromosomal DNA replication.
AB  - Mre11 complex promotes repair of DNA double-strand breaks (DSBs). Xenopus Mre11
      (X-Mre11) has been cloned, and its role in DNA replication and DNA damage
      checkpoint studied in cell-free extracts. DSBs stimulate the phosphorylation and
      3'-5' exonuclease activity of X-Mre11 complex. This induced phosphorylation is
      ATM independent. Phosphorylated X-Mre11 is found associated with replicating
      nuclei. X-Mre11 complex is required to yield normal DNA replication products.
      Genomic DNA replicated in extracts immunodepleted of X-Mre11 complex accumulates
      DSBs as demonstrated by TUNEL assay and reactivity to phosphorylated histone H2AX
      antibodies. In contrast, the ATM-dependent DNA damage checkpoint that blocks DNA
      replication initiation is X-Mre11 independent. These results strongly suggest
      that the function of X-Mre11 complex is to repair DSBs that arise during normal
      DNA replication, thus unraveling a critical link between recombination-dependent
      repair and DNA replication.

PMID- 11511368
TI  - The CF salt controversy: in vivo observations and therapeutic approaches.
AB  - There is controversy over whether abnormalities in the salt concentration or
      volume of airway surface liquid (ASL) initiate cystic fibrosis (CF) airway
      disease. In vivo studies of CF mouse nasal epithelia revealed an increase in
      goblet cell number that was associated with decreased ASL volume rather than
      abnormal [Cl(-)]. Aerosolization of osmolytes in vivo failed to raise ASL volume.
      In vitro studies revealed that osmolytes and pharmacological agents were
      effective in producing isotonic volume responses in human airway epithelia but
      were typically short acting and less effective in CF cultures with prolonged
      volume hyperabsorption and mucus accumulation. These data show that (1) therapies
      can be designed to normalize ASL volume, without producing deleterious
      compositional changes in ASL, and (2) therapeutic efficacy will likely depend on
      development of long-acting pharmacologic agents and/or an increased efficiency of
      osmolyte delivery.

PMID- 11511369
TI  - Cleavage of colicin D is necessary for cell killing and requires the inner
      membrane peptidase LepB.
AB  - Colicin D is known to kill target cells by cleaving tRNA(Arg). A colicin D
      resistant mutant was selected that was altered in the inner membrane leader
      peptidase, LepB. The substituted residue (Asn274Lys) is located close to the
      catalytic site. The mutation abolishes colicin D cleavage but not the processing
      of exported proteins. LepB is required for colicin D cleavage, releasing a small
      C-terminal fragment that retains full tRNase activity. The immunity protein was
      found to prevent colicin D processing and furthermore masks tRNase activity, thus
      protecting colicin D against LepB-mediated cleavage during export. Catalytic
      colicins share a consensus sequence at their putative processing site. Mutations
      affecting normal processing of colicin D abolish cytotoxicity without affecting
      the in vitro tRNase activity.

PMID- 11511370
TI  - Herpes simplex virus glycoprotein D bound to the human receptor HveA.
AB  - Herpes simplex virus (HSV) infection requires binding of the viral envelope
      glycoprotein D (gD) to cell surface receptors. We report the X-ray structures of
      a soluble, truncated ectodomain of gD both alone and in complex with the
      ectodomain of its cellular receptor HveA. Two bound anions suggest possible
      binding sites for another gD receptor, a 3-O-sulfonated heparan sulfate.
      Unexpectedly, the structures reveal a V-like immunoglobulin (Ig) fold at the core
      of gD that is closely related to cellular adhesion molecules and flanked by large
      N- and C-terminal extensions. The receptor binding segment of gD, an N-terminal
      hairpin, appears conformationally flexible, suggesting that a conformational
      change accompanying binding might be part of the viral entry mechanism.

PMID- 11511371
TI  - The polypeptide tunnel system in the ribosome and its gating in erythromycin
      resistance mutants of L4 and L22.
AB  - Variations in the inner ribosomal landscape determining the topology of nascent
      protein transport have been studied by three-dimensional cryo-electron microscopy
      of erythromycin-resistant Escherichia coli 70S ribosomes. Significant differences
      in the mouth of the 50S subunit tunnel system visualized in the present study
      support a simple steric-hindrance explanation for the action of the drug.
      Examination of ribosomes in different functional states suggests that opening and
      closing of the main tunnel are dynamic features of the large subunit, possibly
      accompanied by changes in the L7/L12 stalk region. The existence and dynamic
      behavior of side tunnels suggest that ribosomal proteins L4 and L22 might be
      involved in the regulation of a multiple exit system facilitating cotranslational
      processing (or folding or directing) of nascent proteins.

PMID- 11511372
TI  - Localization of yeast telomeres to the nuclear periphery is separable from
      transcriptional repression and telomere stability functions.
AB  - The left telomere of Saccharomyces chromosome VII was often localized near the
      nuclear periphery, even in cells lacking the silencing proteins Sir3 or Hdf1.
      This association was lost in late mitotic cells and when transcription was
      induced through the telomeric tract. Although in silencing competent cells there
      was no correlation between the fraction of cells in which a telomeric gene was
      repressed and the fraction of cells in which it was localized to the periphery,
      no condition was found where the telomere was both silenced and away from the
      periphery. We conclude that localization of a telomere to the nuclear periphery
      is not sufficient for transcriptional repression nor does it affect the stability
      function of yeast telomeres.

PMID- 11511373
TI  - Excision of group II introns as circles.
AB  - Group II introns are usually removed from precursor RNAs as lariats comprised of
      a circular component and a short 3' tail. We find that group II introns can also
      be excised as complete circles. Circle formation requires release of the 3' exon
      of a splicing substrate, apparently by a trans splicing mechanism. After 3' exon
      release, the terminal uridine of the intron attacks the 5' splice site, releasing
      the 5' exon and joining the first and last intron residues by a 2'-5'
      phosphodiester bond. RNA isolated from yeast mitochondria also contains circles,
      indicating that at least one group II intron (aI2) forms circles in vivo.
      Furthermore, analysis of RNA and DNA from certain mutant yeast strains shows that
      circular DNA introns exist and are produced by reverse transcription of RNA,
      rather than by ectopic homing.

PMID- 11511374
TI  - Sequential assembly of the nucleotide excision repair factors in vivo.
AB  - Here, we describe the assembly of the nucleotide excision repair (NER) complex in
      normal and repair-deficient (xeroderma pigmentosum) human cells, employing a
      novel technique of local UV irradiation combined with fluorescent antibody
      labeling. The damage recognition complex XPC-hHR23B appears to be essential for
      the recruitment of all subsequent NER factors in the preincision complex,
      including transcription repair factor TFIIH. XPA associates relatively late, is
      required for anchoring of ERCC1-XPF, and may be essential for activation of the
      endonuclease activity of XPG. These findings identify XPC as the earliest known
      NER factor in the reaction mechanism, give insight into the order of subsequent
      NER components, provide evidence for a dual role of XPA, and support a concept of
      sequential assembly of repair proteins at the site of the damage rather than a
      preassembled repairosome.

PMID- 11511375
TI  - Intermediates of yeast meiotic recombination contain heteroduplex DNA.
AB  - The formation of heteroduplex DNA features prominently in all models for
      homologous recombination. A central intermediate in the current double-strand
      break repair model contains two Holliday junctions flanking a region of
      heteroduplex DNA. Studies of yeast meiosis have identified such intermediates but
      failed to detect associated heteroduplex DNA. We show here that these
      intermediates contain heteroduplex DNA, providing an important validation of the
      double-strand break repair model. However, we also detect intermediates where
      both Holliday junctions are to one side of the initiating DSB site, while the
      intervening region shows no evidence of heteroduplex DNA. Such structures are not
      easily accommodated by the canonical version of the double-strand break repair
      model.

PMID- 11511376
TI  - Self-excising retroviral vectors encoding the Cre recombinase overcome Cre
      mediated cellular toxicity.
AB  - The Cre-lox system is often used to manipulate sequences in mammalian genomes. We
      have observed that continuous expression of the Cre recombinase in cultured cells
      lacking exogenous lox sites caused decreased growth, cytopathic effects, and
      chromosomal aberrations. Cre mutants defective in DNA cleavage were not geno- or
      cytotoxic. A self-excising retroviral vector that incorporates a negative
      feedback loop to limit the duration and intensity of Cre expression avoided
      measurable toxicity, retained the ability to excise a target sequence flanked by
      lox sites, and may provide the basis of a less toxic strategy for the use of Cre
      or similar recombinases.

PMID- 11511377
TI  - Dynamic changes of touch- and laser heat-evoked field potentials of primary
      somatosensory cortex in awake and pentobarbital-anesthetized rats.
AB  - In this investigation, changes of mechanical- (MEP) and laser-evoked potentials
      (LEP) in rat primary somatosensory cortex during the course of pentobarbital (PB)
      anesthesia were examined. Temporal analysis of changes in the magnitude and
      latency of MEP and LEP, EEG activity, gross motor behaviors, and the tail flick
      response following laser stimulation before, during, and after PB administration
      (50 mg/kg, i.p.) was performed and correlated in chronically implanted rats.
      During the wakeful condition, there were two major cortical components each
      following mechanical stimulation (MEP1 and MEP2, n=17) and laser stimulation
      (LEP1 and LEP2, n=10), respectively. After PB administration, the positive peak
      in MEP1 was enhanced, and all other components disappeared. These components
      returned with different time courses. Two hours after PB administration, when the
      rat had spontaneous movements and flexor reflexes, LEP2 showed reversed polarity.
      MEP2 returned gradually 3 h after PB administration when the rat regained its
      ability to execute coordinated movements. After 4 h, LEP1 began to reappear and
      LEP2 returned to its negative polarity. We found that PB facilitated Abeta fiber
      related cortical evoked potential (MEP1), while differentially inhibited Adelta
      and C fiber-related components (MEP2, LEP1 and LEP2). Characterization of these
      anesthesia-induced changes in cortical output may be useful in studying the
      neural basis of tactile and pain sensations.

PMID- 11511379
TI  - Cortical layer III pyramidal dendritic morphology normalizes within 3 weeks after
      kindling and is dissociated from kindling-induced potentiation.
AB  - This experiment examined the effect of a 3-week rest after electrical kindling on
      kindling-induced potentiation and the morphology of frontal (Fr1) neocortical
      layer III pyramidal cell dendrites in both male and female rats. Repeated
      elicitation of afterdischarge resulted in an increase in the severity of the
      behavioural seizures and afterdischarge duration. The late component of the
      transcallosal evoked responses was significantly larger 1 and 21 days following
      the last kindling session in both male and female rats. Analysis of the Golgi-Cox
      impregnated pyramidal cell dendrites indicated no significant difference in the
      amount of apical and basilar dendritic, branching, length, and spine density in
      both male and female rats, relative to their respective control groups, 21 days
      following the last kindling session. There was, however, one exception, the male
      group showed a significant increase in apical spine density. The persistent
      expression of kindling-induced potentiation appears to be dissociated from the
      renormalized pyramidal cell dendritic morphology.

PMID- 11511378
TI  - Inhibitory effect of 17beta-estradiol in the parabrachial nucleus is mediated by
      GABA.
AB  - In the present investigation, electrophysiological recordings of thalamic relay
      neurons were used to investigate the role of estrogen as a modulator of visceral
      afferent information through the PBN to forebrain structures. Experiments were
      done in anaesthetized (sodium thiobutabarbitol; 100 mg/kg) male and
      ovariectomized female rats supplemented for 7 days prior with either 17beta
      estradiol (OVX-E(2)) or saline (OVX-S). A portion of the right cervical vagus was
      isolated for the electrical activation (0.8 Hz, 2 ms duration) of visceral
      afferents. The evoked single and multi-unit activity was recorded via a recording
      electrode in the ventrobasal thalamus. Exogenous microinjection of 17beta
      estradiol (0.1, 0.25 and 0.5 microM; 200 nl) into the parabrachial nucleus (PBN)
      produced a significant, dose-dependent attenuation in the magnitude of visceral
      afferent activation-evoked responses of neurons recorded in the thalamus in both
      male and OVX-E(2) groups. No effect on evoked thalamic activity was observed
      following injection of estrogen into the PBN of OVX-S animals. Co-injection of
      estrogen with the GABA(A) receptor antagonist, bicuculine (0.1 microM; 200 nl)
      but not phaclofen (GABA(B); 0.1, 0.5 or 1 microM; 200 nl) resulted in an increase
      in the evoked thalamic response in males (55+/-11%) and OVX-E(2) female (68+/
      15%) rats. These studies suggest that estrogen inhibits neurotransmission in the
      PBN via an interaction with the GABA(A) receptor to modulate the flow of visceral
      information to the thalamus.

PMID- 11511380
TI  - Long-term brain metabolic alterations in exogenous Cushing's syndrome as
      monitored by proton magnetic resonance spectroscopy.
AB  - The effects of exogenous Cushing's syndrome on the brain metabolism were
      investigated by proton magnetic resonance spectroscopy (MRS). Thirteen patients
      having been treated for 2 to 22 years with prednisone were recruited. On the
      average, none of the metabolites (NAA, Cr, Cho and mI) were significantly
      different from those of 40 normal subjects in any of the three regions studied:
      frontal area, thalamus and temporal area. However, the Cho/H(2)O ratios were
      found to decrease significantly in the thalamic area as a function of treatment
      period (-1.3%/year). In the frontal and temporal areas, decreases of the
      Cho/H(2)O ratios were measured with treatment period but they did not reach
      statistical significance. Effects on Cho levels can be related to those observed
      for patients with endogenous Cushing's syndrome and suggest an impairment at the
      membrane level. The Cho/H(2)O reductions were not found to be dose- or age
      dependent. Other metabolite ratios did not vary with treatment period, dose or
      age.

PMID- 11511381
TI  - Role of 5-HT(2) receptor subtypes in depletion of 5-HT induced by p
      chloroamphetamine in the mouse frontal cortex.
AB  - A serotonin (5-hydroxytryptamine, 5-HT)-releasing drug, p-chloroamphetamine
      elicited decreases in 5-HT levels in the mouse frontal cortex. 5-HT reduction
      elicited by p-chloroamphetamine was inhibited by the 5-HT(2A/2B/2C) receptor
      antagonist, LY 53857 and the 5-HT(2A) receptor antagonist, ketanserin. However,
      the 5-HT(2B/2C) receptor antagonist, SB 206553, enhanced it. LY 53857 and
      ketanserin can inhibit hyperthermia elicited by p-chloroamphetamine, although SB
      206553 enhances it. The effects of the 5-HT(2) receptor antagonists on
      neurotoxicity are very similar to those on hyperthermia. Since hyperthermia
      facilitates neurotoxicity induced by amphetamine analogue, these 5-HT(2) receptor
      antagonists may modify 5-HT depletion induced by p-chloroamphetamine through
      responses to body temperature.

PMID- 11511382
TI  - 3alpha,5alpha-THP in the raphe magnus attenuates PTZ-induced myoclonic seizures.
AB  - Whether progesterone (P(4)) and its metabolite, 5alpha-pregnan-3alpha-ol-20-one
      (3alpha,5alpha-THP) have anti-seizure effects through actions in the raphe magnus
      (NRM) was investigated. Ovariectomized, Long-Evans rats with unilateral implants
      into the NRM of P(4) or its metabolite, 5alpha-pregnan-3alpha-ol-20-one
      (3alpha,5alpha-THP) had a significantly lower incidence of myoclonic seizures and
      less EEG activity following pentylenetetrazol (PTZ; 70 mg/kg, IP) administration
      than did rats with control implants. Progestin implants that missed the NRM were
      not effective at reducing ictal activity. Following P(4) implants to the NRM
      levels of P(4), and following P(4) and 3alpha,5alpha-THP implants to the NRM,
      3alpha,5alpha-THP levels in the ventral hindbrain were increased above those seen
      in rats with control implants. These data suggest that progestins' anti-seizure
      effects in the NRM may be involve actions of 3alpha,5alpha-THP.

PMID- 11511383
TI  - Glucose-6-phosphate dehydrogenase supports the functioning of the synapses in rat
      cerebellar cortex.
AB  - This study investigates heterogeneous glucose-6-phosphate dehydrogenase (G6PD)
      expression in the rat cerebellar cortex. G6PD activity and its electrophoretic
      pattern, evaluated on the cerebellar homogenate, were found to be similar to
      those of other brain areas. However, histochemical and immunohistochemical
      analyses revealed that the highest expression of G6PD activity and protein was in
      Purkinje's cells, followed by the molecular and granular layers. Electron
      microscopy analysis showed that, in Purkinje's cells, the G6PD reaction products
      were concentrated in the neurites while in the basket cells in the cell body. The
      granules showed a weaker activity everywhere. The quantitative distribution of
      G6PD is discussed in the light of the neurochemical function of these cells.

PMID- 11511384
TI  - Hippocampal sympathetic ingrowth occurs following 192-IgG-Saporin administration.
AB  - Electrolytic lesions of the medial septal region leads to an unusual neuronal
      reorganization in which peripheral sympathetic fibers, originating from the
      superior cervical ganglia, grow into the cholinergically denervated areas of the
      hippocampus. Since these lesions disrupt cells and fibers of passage which are
      non-cholinergic, there has been a debate whether Hippocampal Sympathetic Ingrowth
      is due only to cholinergic denervation of the hippocampus. Using the intraseptal
      administration of 192-IgG-Saporin, a specific cholinergic neurotoxin, we have
      found that hippocampal sympathetic ingrowth occurs in the cholinergically
      denervated hippocampus at 4, 8 and 12 weeks post Saporin injection. These results
      clearly suggest that hippocampal sympathetic ingrowth is due to the specific loss
      of the cholinergic projection from the medial septum.

PMID- 11511385
TI  - Leukaemia inhibitory factor abrogates Paclitaxel-induced axonal atrophy in the
      Wistar rat.
AB  - A prominent side effect of Paclitaxel chemotherapy is sensorimotor peripheral
      neuropathy. Leukaemia inhibitory factor (LIF) supports the survival and regrowth
      of axotomised sensory and motor neurons and we therefore investigated if
      systemically administered LIF abrogated Paclitaxel-induced neuropathy. We found
      that whereas animals administered Paclitaxel alone exhibited a significant
      decrease in the percentage of large myelinated axons, this reduction was
      prevented by the co-administration of LIF.

PMID- 11511386
TI  - Novel purinergic sensitivity develops in injured sensory axons following sciatic
      nerve transection in rat.
AB  - Teased fibers were made from 153 spontaneous A afferents ending in sciatic nerve
      end neuromas of 3-14 days standing, 21 A afferents from intact sensory endings in
      the contralateral sciatic nerve, and 50 intact A afferents from the sciatic nerve
      in intact rats. Ninety-two percent of the injured fibers responded to adenosine
      5'-triphosphate (ATP) (i.v.). However, few fibers from the contralateral nerve or
      nerves from intact animals responded to ATP. P2 receptor antagonist suramin or
      reactive blue 2 blocked the ATP-induced response in 76% of the fibers tested,
      whereas the P1 receptor antagonist aminophylline blocked the ATP-evoked effect in
      only 18% of the fibers tested. Sympathectomy did not affect the ATP-induced
      effects in injured axons. Close-arterial injection of ATP caused similar results
      as i.v. injection of ATP. The present study suggests that a novel purinergic
      sensitivity is developed at the injury site after sciatic nerve transection in
      rats, which may play a role in neuropathic pain under some conditions such as
      sympathetic activation.

PMID- 11511387
TI  - Influence of anesthesia on brain distribution of [(11)C]methamphetamine in
      monkeys in positron emission tomography (PET) study.
AB  - We investigated the influence of anesthesia on the brain distribution of
      [11C]methamphetamine (MAP) obtained by the positron emission tomography (PET)
      using the normal rhesus monkeys. We clarified that the brain uptake of [11C]MAP
      under halothane anesthesia was faster and higher than that under pentobarbital.
      The difference of the effect of anesthesia is an important problem in
      pharmacokinetic study in PET with experimental animals.

PMID- 11511388
TI  - Dissociated functional recovery in parkinsonian monkeys following transplantation
      of astroglial cells.
AB  - Bilateral astroglial transplantation into the neostriatum of 1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys resulted in significant
      performance improvement in a spatial delayed response task, but failed to modify
      perseveration in an object retrieval detour task, or to improve motor clinical
      rating. Results suggest that brain circuits subserving various motor and
      cognitive performances can be functionally dissociated, and that remaining
      resources for the reorganization of neural circuits involved in spatial working
      memory performance in parkinsonian monkeys, appear to be responsive to striatal
      transplantation of subcultured, fetal striatal astroglial cells.

PMID- 11511389
TI  - Ionic currents in PC12 cells differentiated into neuron-like cells by a cultured
      sciatic nerve conditioned medium.
AB  - The present work deals with the identification of the ionic currents found in
      PC12 cells differentiated into neuron-like cells by a 9-11-day cultured-sciatic
      nerve conditioned medium (CM). PC12 whole-cell currents were measured after
      chronic exposure to CM. The results obtained in these CM-treated cells reveal
      that the functional expression of Ca(2+) currents is increased, that Na+ currents
      are not affected, and that a transient K+ current and a K+ delayed rectifier (K+
      dr) current are increased. The combination of nifedipine and omega-conotoxin GVIA
      (omega-CgTX) does not block completely the increased functional expression of the
      Ca(2+) current. The remaining current is blocked by omega-agatoxin TK indicating
      that P/Q-type channels are additionally contributing to the increase in Ca(2+)
      current. NGF-treated PC12 cells, used as positive controls, confirm that NGF
      increases the expression of voltage-dependent Na+ currents and of Ca(2+)
      currents. In addition, we found that NGF also increases a K+ dr-type current in
      these cells. The results obtained with the CM might be due to a molecule or a
      mixture of molecules released into the medium by the 9-11-day cultured sciatic
      nerves.

PMID- 11511390
TI  - Response dynamics of entorhinal cortex in awake, anesthetized, and bulbotomized
      rats.
AB  - The generation of oscillatory activity may be crucial to brain function. The
      coordination of individual neurons into rhythmic and coherently active
      populations is thought to result from interactions between excitatory and
      inhibitory cells mediated by local feedback connections. By using extracellular
      recording wires and silicon microprobes to measure electrically evoked damped
      oscillatory responses at the level of neural populations in the entorhinal
      cortex, and by using current-source density analysis to determine the spatial
      pattern of evoked responses, we show that the propagation of activity through the
      cortical circuit and consequent oscillations in the local field potential are
      dependent upon background neural activity. Pharmacological manipulations as well
      as surgical disconnection of the olfactory bulb serve to quell the background
      excitatory input incident to entorhinal cortex, resulting in evoked responses
      without characteristic oscillations and showing no signs of polysynaptic
      feedback. Electrical stimulation at 200 Hz applied to the lateral olfactory tract
      provides a substitute for the normal background activity emanating from the bulb
      and enables the generation of oscillatory responses once again. We conclude that
      a non-zero background level of activity is necessary and sufficient to sustain
      normal oscillatory responses and polysynaptic transmission through the entorhinal
      cortex.

PMID- 11511391
TI  - Superoxide-induced nitric oxide release from cultured glial cells.
AB  - Nitric oxide (NO) has been implicated as a potential contributor to neural cell
      death in a variety of neurological conditions. Cultured glial cells were exposed
      to extracellular superoxide generated by the action of xanthine oxidase on
      xanthine. In this experimental paradigm, both C6 glioma cells and primary
      astrocytes from rat cerebral cortex produced a rapid release of nitric oxide,
      measured using an NO specific electrode, in response to the applied superoxide
      stimulus. Application of a superoxide scavenger, or over-expression of Cu/Zn
      superoxide dismutase decreased the observed NO release. Authenticity of the NO
      signal was confirmed by the addition of the NO scavenger 2-(carboxyphenyl)
      4,4,5,5-tetramethyllimidazoline-1-oxyl 3-oxide (carboxy-PTIO), which abolished
      the observed NO release without affecting simultaneously measured superoxide.
      Therefore, we suggest that glial cells may produce NO under free radical
      stimulation, which may be relevant to several neurological disorders where
      superoxide radicals are generated in the vicinity of glia. This would be
      predicted to result in the release of NO, which may exert toxic effects on
      neighbouring cells.

PMID- 11511392
TI  - Alpha synuclein aggregation: is it the toxic gain of function responsible for
      neurodegeneration in Parkinson's disease?
AB  - Protein aggregation appears to be the common denominator in a series of distinct
      neurodegenerative diseases yet its role in the associated neuronal pathology in
      these various conditions remains elusive. In Parkinson's disease, localization of
      alpha synuclein aggregates within intracellular Lewy body occlusions represent a
      major hallmark of this disorder and suggest that such aggregation may play a
      causative role in the resulting dopaminergic cell loss. In this Viewpoint
      article, recent data is reviewed related to how alpha synuclein aggregation may
      occur, what cellular events might be responsible, and how this may interfere with
      normal cellular function(s). It appears likely that while aggregation of alpha
      synuclein may interfere with its normal function in the cell, this is not the
      primary cause of the related neurodegeneration.

PMID- 11511393
TI  - Leptin signaling and aging: insight from caloric restriction.
AB  - Organisms have evolved neuroendocrine and metabolic response systems to enhance
      survival during periods of food shortage, which occur frequently in nature. The
      anti-aging effect of caloric restriction (CR) might derive from these adaptive
      responses to maximize organism survival. The present article discusses the
      potential role for leptin, a hormone secreted from adipocytes, as a key signal
      that induces the adaptive responses relevant to CR. Evidence indicates that a CR
      induced reduction of the plasma leptin concentration suppresses the gonadal,
      somatotropic, and thyroidal axes, and activates the adrenal axis. Metabolic
      adaptation, a shift in fuel utilization mainly conducted in the liver, seems to
      require leptin signaling. Although alternative signaling pathways might also
      mediate the anti-aging effects of CR, leptin signaling could be a substantial
      pathway involved in these effects. Molecular dissection of the mechanisms
      underlying the effects of CR will contribute to a better understanding of the
      aging process, leading to the extension of a healthy lifespan in humans.

PMID- 11511394
TI  - Neutrophil ageing and immunesenescence.
AB  - As humans age, their morbidity and mortality from infection increases, their
      response to vaccination declines and they have an increased incidence of
      inflammatory diseases and cancer. The reasons for these effects are clearly
      complex, but reduced efficiency of the innate and adaptive immune system is
      likely to be important in the pathology of old age. Age-related changes in the
      adaptive immune system are well-documented and include alterations in T cell
      phenotype and effector functions and a reduced ability of B cells to produce high
      affinity antibody. In contrast, the innate immune system has been less well
      researched and the perception amongst many immunogerontologists is that this
      branch of the immune system is only moderately affected by age. However, it is
      becoming increasingly clear that the adaptive and innate immune systems co
      operate at several levels to ensure the optimal immune response and any decline
      in adaptive immunity will impact upon the function of the innate immune system
      and vice-versa. Here, we review the literature concerning intrinsic age-related
      changes in neutrophil responses and consider how changes in lymphocyte function
      with age might further compromise efficiency of neutrophil function.

PMID- 11511395
TI  - Does functional depletion of stem cells drive aging?
AB  - The regenerative power of stem cells has raised issues about their relation to
      aging. We focus on the question of whether a decline in the function of stem
      cells may itself be a significant feature of aging. The question is implicitly
      two-fold: does functional depletion of stem cells affect the accumulation of
      aging-related deficits, and--whether or not depletion is significant--can
      activation of stem cells alleviate deficits? Two types of system are considered:
      1) the exhaustible pool of ovarian follicles. The depletion of follicles leads to
      the aging-related phenomenon of menopause; and 2) the reserve of hematopoietic
      stem cells. Substantial numbers are sustained throughout life, but in mouse
      models, endogenous replicative activity has been shown to decline sharply with
      age. We discuss the possible implications of these observations for the rate of
      aging and the prospects for intervention.

PMID- 11511396
TI  - Gene therapy and the aging nervous system.
AB  - In recent years, the first attempts have been made to apply gene transfer
      technology to protect neurons from death following neurological insults. There
      has been sufficient progress in this area that it becomes plausible to consider
      similar gene therapy approaches meant to delay aspects of aging of the nervous
      system. In this review, we briefly consider such progress and how it might be
      applied to the realm of the aging brain. Specifically, we consider: (a) the means
      of delivery of such therapeutic genes; (b) the choice of such genes; and (c)
      technical elaborations in gene delivery systems which can more tightly regulate
      the magnitude and duration of transgene protection.

PMID- 11511397
TI  - The role of fat cell derived peptides in age-related metabolic alterations.
AB  - Aging in humans is associated with alterations in body fat distribution and a
      parallel gradual increase in the prevalence of atherosclerotic cardiovascular
      disease, as well as mortality of all causes. Because of nutrient cost,
      availability, and the sedentary life-style, half of the western world population
      has fat mass in excess of 30% of the body weight that weighs 3-4 times more than
      the fat mass of lean subjects. Recent discoveries of various hormones, cytokines
      and complement factors secreted by adipose cells opened a new avenue of research,
      looking at the role of these fat derived peptides in different conditions. We
      will focus here on the potential role of fat tissue in different physiological
      and physiopathological conditions associated with age-related metabolism and risk
      factors for diseases. We will also exemplify how body fat capacity, distribution
      and function can be directly linked, and may play a central role in energy
      metabolism and homeostasis, atherosclerosis, and possibly in the defense against
      cancer. We hypothesize that biological pathways involved in nutrient regulation
      in fat tissue may be important in inducing longevity in calorie restricted
      animals.

PMID- 11511398
TI  - Mitochondrial DNA mutations, oxidative stress, and aging.
AB  - Advances in understanding of mitochondrial physiology and genetics in relation to
      pathology have exploded in the last decade. Paralleling this increase has been an
      active debate about the role of mitochondrial oxidative stress with regard to
      mitochondrial DNA mutations, aging, and disease. We discuss in a historical
      context the rapid progress in our understanding of the role of mitochondrial DNA
      mutations in disease, mitochondrial oxidative stress in aging, and the potential
      interplay between these two phenomena.

PMID- 11511399
TI  - The process of aging changes the interplay of the immune, endocrine and nervous
      systems.
AB  - The immune, endocrine and nervous systems interact with each other by means of
      cytokines, hormones and neurotransmitters. Interaction is dependent on specific
      receptors and respective signaling pathways in target cells. During aging,
      changes occur on many levels of these global systems which depend on oxidative
      damage, non-enzymatic glycosylation, mitochondrial mutations, defects in cell
      cycle control, mitotic dysregulation, genome instability, telomere shortening and
      other chromosomal pathologies. An alteration of the numerical value of a
      parameter of one system can lead to changes of the numerical value of a variable
      of another system. In a non-linear dynamic process these changes can contribute
      to the aging phenotype. Although it is extremely difficult to dissect linear
      interrelations of three global systems during aging, this review attempts to
      identify some simple linear pathways. Furthermore, it is demonstrated that
      chronic inflammatory diseases may accelerate the aging process. This review also
      reveals that new statistical and computational methods are necessary to unravel
      the complexity of the aging process.

PMID- 11511400
TI  - Altered T cell signalling in ageing.
AB  - T cell responses are altered in the aged in a manner usually interpreted as
      detrimental to host defences against infectious agents and possibly also against
      cancer. T cell dysregulation may be caused by any or a combination of stem cell
      deficits, compromised T cell differentiation, inefficient antigen processing and
      presentation by antigen presenting cells, suboptimal processing of the antigenic
      signal by T cells or inability of the T cell to respond appropriately thereafter.
      This review will focus on altered T cell signalling in ageing, encompassing not
      only alterations in signal transduction by the antigen-specific T cell receptor,
      but changes in the balance of positive and negative T cell costimulation and the
      resultant modified cytokine environment, the response to which is itself altered
      in ageing.

PMID- 11511401
TI  - Transgenic invertebrate models of age-associated neurodegenerative diseases.
AB  - Transgenic Drosophila melanogaster and Caenorhabditis elegans strains have been
      engineered to express human proteins associated with neurodegenerative diseases.
      These model systems include transgenic animals expressing beta-amyloid peptide
      (Alzheimer's disease), polyglutamine repeat proteins (Huntington's disease,
      Spinocerebellar ataxia), and alpha-synuclein (Parkinson's disease). In most of
      these invertebrate models, some aspects of the human diseases are reproduced.
      Although expression of all these proteins in transgenic mice has been
      instructive, the invertebrate models offer experimental advantages (e.g. forward
      genetic screens) that can potentially address some of the outstanding questions
      regarding the cellular processes underlying these diseases. This review considers
      what has been learned from these invertebrate models, and speculates what further
      insight may be gained from them.

PMID- 11511402
TI  - The relevance of hierarchies, territories, defeat for depression in humans:
      hypotheses and clinical predictions.
AB  - BACKGROUND: Hierarchical and territorial behaviour are widespread in animals and
      humans. The consequences of defeat have been linked to depression in humans.
      However, hierarchical and territorial behaviours are not mentioned in ICD10 or
      DSM1V. I therefore investigated the coverage in relevant textbooks. METHOD: I
      searched the indices of books on Animal Behaviour, General Psychology and General
      Psychiatry for entries on Hierarchy, Territory and Dominance. RESULTS: A paradox
      is revealed. Hierarchical and territorial behaviour are widespread in both
      animals and humans but are neglected in textbooks of human behaviour and mental
      problems. Four hypotheses are put forward to explain this paradox and explore its
      implications. 1. That hierarchical and territorial behaviours evolved before
      human consciousness. They are available to consciousness but not in the forefront
      of awareness. 2. That human hierarchical and territorial behaviour are overlaid
      by a cultural veneer of manners, which conceal the true state of affairs. 3. That
      humans have internal, mental, hierarchical aims in addition to external physical
      hierarchical aims. 4. That failure to achieve internal hierarchical aims may
      produce diminution of well being and changes in behaviour by the same biological
      mechanisms that are active in external hierarchical defeat. Three testable
      predictions follow from these hypotheses. 1. That there are common genetic
      factors and similar patterns of brain activity in homologous structures during
      hierarchical and territorial behaviour in man, primates and lower vertebrates. 2.
      That brain structures involved in external hierarchical conflict, consciousness
      and imagery will be active during internal hierarchical conflict. 3. Defeat of
      internal hierarchical aims produce depressed mood and satisfying alternative
      hierarchical aims are protective. Case examples are given to illustrate the
      existence of, and the consequences of defeat on, internal hierarchies.
      LIMITATIONS: These hypotheses and predictions are theoretical and require
      confirmation or refutation by neuroimaging and prospective studies. CONCLUSIONS:
      A neglect of human hierarchical behaviour by clinicians is suggested and
      discussed. The concept of internal hierarchies, if confirmed, may throw light on
      human striving, the emotions of defeat and the therapy of depression.

PMID- 11511403
TI  - Determinants of functional outcome and healthcare costs in bipolar disorder: a
      high-intensity follow-up study.
AB  - BACKGROUND: Review of published studies reveals few data regarding determinants
      of the poor functional outcome and high healthcare costs that are characteristic
      of bipolar disorder. In order to identify potential mechanisms, critical to
      designing optimal treatment strategies, this longitudinal study investigated (a)
      the degree to which disease outcome is correlated with functional outcome and
      direct treatment costs, and (b) whether similar demographic or clinical
      characteristics predict disease and functional outcome and healthcare costs.
      METHODS: Disease and functional outcome were assessed in bimonthly structured
      interviews over 48 weeks in 43 outpatient veterans with bipolar disorder. Direct
      mental health treatment costs from the VA perspective were determined from the VA
      database and patient interview. Regression analysis was used to determine
      association among the three outcome domains, and to identify clinical or
      demographic variables that predicted each of the three domains. RESULTS:
      Functional outcome was correlated with depressive, but not manic, symptoms during
      follow-up. Costs were not correlated with any measure of disease or functional
      outcome. Several demographic, but not clinical, characteristics predicted
      functional outcome. In contrast, several clinical, but not demographic,
      characteristics predicted symptom status. No predictors were associated with
      direct treatment costs. LIMITATIONS: Subjects were predominantly male veterans of
      relatively homogeneous social class, followed prospectively for approximately one
      year in a clinic designed specifically to minimize barriers to care. CONCLUSIONS:
      Data from this and prior studies indicate that ongoing depressive symptoms are
      strongly associated with functional outcome, although substantial variance
      remains unexplained. Optimal models to explain functional outcome and healthcare
      costs will need to address factors besides simply disease severity and
      chronicity. The authors present a heuristic paradigm for understanding both the
      research and therapeutic aspects of these findings.

PMID- 11511404
TI  - Adherence to treatment regimen in depressed patients treated with amitriptyline
      or fluoxetine.
AB  - OBJECTIVE: Non-compliance presents a constant challenge to effective therapy.
      Many studies only investigate early treatment discontinuation and not other
      measures like adherence to treatment regimen. We compared adherence in depressed
      patients using either a selective serotonin reuptake inhibitor (fluoxetine) or a
      tricyclic antidepressant (amitriptyline), and examined its clinical relevance
      through adverse events, drop-out rates, and outcome. Adherence was measured
      electronically with the MEMS (Medication Event Monitoring System). DESIGN: Nine
      week double blind, randomized controlled trial. SETTING: Ambulatory psychiatric
      care. PATIENTS: Random sample of 66 depressed (DSM-III-R criteria) patients.
      INTERVENTION: Fluoxetine 20 mg or amitriptyline 150 mg. MAIN OUTCOME MEASURES:
      Time course of adherence and its relation to severe adverse events, drop-outs and
      outcome. RESULTS: Non-adherence to the treatment regimen occurred frequently in
      both treatment groups: 31% of patients had at least one 3-day drug holiday, and
      34% of patients had at least one episode of three pills in a 24-h period. Over
      consumption occurred more frequently during the early phases of treatment while
      under-consumption occurred more frequently during the later phases. Patients on
      amitriptyline (P=0.03) and patients with a higher pill intake (P=0.01)
      experienced more severe adverse events. Patients on amitriptyline (P=0.009) and
      patients with a lower adherence to the treatment regimen (P=0.004) discontinued
      from treatment more frequently. The final Hamilton score was significantly
      predicted by a longer duration of treatment and by a better adherence, but only
      in amitriptyline users. CONCLUSIONS: Non-adherence to the treatment regimen has
      important clinical consequences. Pharmacodynamics and human behavior predict risk
      for severe adverse events and drop-outs. Moreover, in amitriptyline users but not
      in fluoxetine users, better adherence predicts a better outcome.

PMID- 11511405
TI  - Diurnal variations in suicide by age and gender in Italy.
AB  - BACKGROUND: Recent Italian statistics on suicide distribution by time of day also
      report data on gender and age of victims, factors which have been shown to
      influence the seasonal distribution of suicide and which could also affect the
      influence of biological circadian rhythms on suicidal behaviour. This study aims
      to identify and evaluate any diurnal variations that may be present in suicide
      occurrence by age and gender in Italy, considering data from 1994 to 1997.
      METHODS: The null hypothesis that there are no variations in the distribution of
      suicides by time of day (or over the three major periods of the day: morning,
      afternoon, evening/night) was tested with the chi2 goodness-of-fit test and with
      ANOVA. RESULTS: A clear diurnal variation in the distribution of suicides over
      time can be observed for both genders, with a peak in the late morning (08:00
      11:00 h), and a subsequent decrease to a trough in the night hours. This trend
      varies with age for both genders: in particular, the age groups 45-64 and 65+
      show a clear suicide peak in the morning (08:00-11:00 h), whereas younger people
      have a peak number of suicides in the late afternoon (16:00-19:00 h). Adults (25
      44 years old) show an intermediate trend, with a less pronounced peak between the
      morning and early afternoon hours. The observed trend is more marked among males;
      however, the distribution of suicides by time of day is clearly congruent by age
      between both genders. CONCLUSIONS: Diurnal variation in suicide occurrence by age
      group may be affected by factors distributed unevenly across age groups. In
      particular, age distribution of disorders leading to suicidal ideation, and the
      sensitivity of biological systems of different age groups to environmental cues
      may affect each group's risk of suicide. Socio-relational factors are also likely
      to contribute to diurnal variation in suicide risk by age and gender. Children
      and adolescents can generally be presumed to be at school during the morning,
      therefore their opportunity for self-harm is restricted to afternoon hours. The
      elderly, on the other hand, may find themselves alone in the morning, when family
      and friends spend more time away from home due to daily work activities.
      LIMITATIONS: Data are based on time of death and not on presumed time of the
      suicidal act. For suicides committed by certain methods (e.g., poisoning) there
      may be a considerable difference between time of act and time of death. CLINICAL
      RELEVANCE: The existence of a temporal window in suicide risk implies an
      improvement in the surveillance of people at risk of suicide and greater
      attention to chronobiological factors affecting those suffering from mental
      disorders leading to suicide ideation.

PMID- 11511406
TI  - Mortality in affective disorders.
AB  - BACKGROUND: To investigate the mortality rates in affective disorders due to
      unnatural and natural causes with respect to illness subtype and social
      demographic features. METHODS: Mortality data were determined from a prospective
      study of 354 outpatients with affective disorders during a follow-up period of 5
      years. Death from natural and unnatural causes was compared to sex- and age
      specific expectations in the general population. Standardized mortality rates
      (SMR) in diagnostic subgroups and the influence of social-demographic features
      were investigated. RESULTS: The observed 30 deaths represented nearly three times
      (SMR, 2.9) the number expected on the basis of age- and sex-standardized
      reference population rates. Death from natural causes occurred with the same rate
      as expected (SMR, 1.0), death from unnatural causes was 28.8 times higher than
      expected. Women with affective disorders had a considerable high risk to die from
      unnatural causes (SMR, 47.1). A significant excess of unnatural death was found
      in all subtypes of affective disorders, particularly in recurrent major
      depressive episodes (SMR, 46.7). LIMITATIONS: The sample was restricted in size.
      Therefore subgroup differences and multiple relationships of risk factors could
      not be analyzed with high statistical power. CONCLUSIONS: The results corroborate
      earlier findings of excess mortality in major affective disorders and strengthen
      the view that suffering from recurrent major depression confers per se an
      important biological risk for suicide. Natural causes of death in affective
      disorders are comparable to expectations from reference populations. Social
      demographic characteristics may contribute to an additional risk of premature
      death by suicide, particularly in women.

PMID- 11511407
TI  - Cross-talk between PKA and PKC in human fibroblasts: what are the
      pharmacotherapeutic implications?
AB  - BACKGROUND: The present study was designed to confirm or refute in human
      fibroblasts the hypothesized cross-talk elicited via neurotransmitter
      transduction cascades at the level of protein kinase mediated phosphorylation of
      the nuclear transcription factor CREB. METHODS: Human fibroblasts from normal
      control subjects were subcultured and incubated at confluency after five growth
      passages with isoproterenol (stimulation of PKA mediated phosphorylation) and/or
      phorbol 12-myristate 13-acetate (PMA) (stimulation of PKC mediated
      phosphorylation) followed by the determination of nuclear CREB-P by
      immunoblotting, enhanced chemiluminescence and quantitation of the autoradiograms
      by laser densitometry. RESULTS: Using the nuclear transcription factor CREB as a
      target, both the activation of the cyclic AMP-PKA pathway by isoproterenol and
      the activation of the PKC pathway by PMA caused phosphorylation of nuclear CREB.
      This phosphorylation is additive in nature and appears to occur at the same
      molecular site, serine133 of CREB. CONCLUSIONS: The present results in human
      fibroblasts demonstrate that the hypothesized cross-talk at the level of protein
      kinase mediated phosphorylation of transcription factors is no longer
      hypothetical. Since it is the phosphorylation of nuclear CREB that determines its
      dimerization and transcriptional activation of programs of CRE containing genes,
      the results suggest that this convergence of the neurotransmitter signals may be
      the critical mechanism in gene expression following the administration of
      antidepressant drugs that affect noradrenergic, serotonergic or both transduction
      cascades. The results may also provide a rationale for the apparent superior
      clinical efficacy of dual uptake inhibitors.

PMID- 11511408
TI  - Long-term naturalistic treatment of depressive symptoms in bipolar illness with
      divalproex vs. lithium in the setting of minimal antidepressant use.
AB  - OBJECTIVE: Risks have been associated with the long-term use of antidepressant in
      the treatment of bipolar disorder. We review our naturalistic experience with
      divalproex versus lithium in treating depressive symptoms of bipolar illness.
      METHOD: All patients with bipolar disorder treated with lithium or divalproex
      were identified in a university outpatient psychiatry clinic sample over one year
      (n=38 patients, 41 treatment trials). Treatment response was based on standard
      prospective symptom rating scales. Mean duration of follow-up was 90 weeks.
      RESULTS: Lithium and divalproex were equally effective and tolerated in the total
      sample. Antidepressant effects were noted despite sparing use of standard
      antidepressant agents (19% received them). Lithium non-responders responded well
      to divalproex (50%), and vice versa (44%). Divalproex monotherapy (24%) was more
      common than lithium monotherapy (7%, P=0.07) and was notably effective in
      treating depressive symptoms, with a 7/10 response on the CGI-BP and improvement
      on the HDRS (14.8+/-9.2 to 7.6+/-7.8, P=0.003, duration of prospective follow up
      26.7 weeks). CONCLUSIONS: Lithium and divalproex were equally effective and
      tolerated in this naturalistic sample, but responders may represent distinct
      subgroups. Both agents, but particularly divalproex, demonstrated long-term
      antidepressant effects, with limited adjunctive standard antidepressant use.

PMID- 11511409
TI  - Comorbidity burden and its impact on psychosocial morbidity in depressed
      outpatients.
AB  - BACKGROUND: Many studies have examined the co-occurrence of depression and one or
      two nondepressive disorders; however, little research has looked at broad
      spectrum comorbidity (i.e., comorbidity across several diagnostic categories) in
      depressed patients. Research on diagnostic practices in routine clinical settings
      -in which unstructured interviewing is the norm--suggests that comorbid
      conditions are often not detected [Zimmerman, M., Mattia, J. 1999. Psychiatric
      diagnosis in clinical practice: Is comorbidity being missed? Compr. Psychiatry,
      40, 182-191]. In this study we examined the independent impact of different
      comorbid diagnostic categories on psychosocial morbidity in psychiatric
      outpatients with Major Depressive Disorder (MDD). METHODS: Participants were
      drawn from a pool of 1000 psychiatric outpatients interviewed with the Structured
      Clinical Interview for DSM-IV diagnoses (SCID-IV; [First, M.B., Spitzer, R.L.,
      Williams, J.B.W., Gibbon, M., 1995. Structured Clinical Interview for DSM-IV
      (SCID). American Psychiatric Association, Washington, D.C.]). We compared the
      demographics, clinical characteristics, and psychosocial functioning of depressed
      outpatients with and without different axis I comorbidities, then conducted
      multivariate analyses to determine the respective impact of comorbid axis I
      disorders. RESULTS: Three hundred and seventy-three patients had a principal
      diagnosis of unipolar MDD. One hundred twenty-nine (34.6%) were diagnosed with
      MDD only, and 244 (65.4%) had MDD and at least one other axis I disorder.
      Comorbidity was associated with longer duration of index episode, more
      psychiatric morbidity, and more social and occupational impairment. There was
      also a significant relationship between increasing number of comorbid axis I
      disorders and greater psychiatric and psychosocial impairment. In regression
      analyses, comorbidity burden (i.e., the number of comorbid axis I disorders)
      showed the strongest relation to psychiatric and psychosocial impairment.
      LIMITATIONS: This is not a random sample of depressed outpatients and, thus, may
      not be generalizable to all outpatients with depression. Second, Axes II and III
      comorbidity were not assessed. CONCLUSIONS: Comorbidity burden showed the
      strongest relation to impairment over and above the presence of any particular
      class of disorders.

PMID- 11511410
TI  - Prognostic factors in major depression: a long-term follow-up study of 323
      patients.
AB  - BACKGROUND: Optimal long-term treatment of major depression should assess the
      background factors affecting remission and recurrent episodes. The duration and
      number of previous depressive episodes has been shown to be important for
      recurrence. This long-term prospective study of patients with major depression
      assessed the prognostic effect of variables related to childhood, social life and
      occupation. METHODS: The study examined 323 patients in two follow-up
      examinations 12-25 years from the initial examination to the second follow-up.
      Stepwise logistic regression was used to evaluate the prognostic effect for
      depression at the second follow-up. RESULTS: The risk of depression at the second
      follow-up was associated with several psychosocial factors in childhood, female
      gender, social isolation and a negative attitude towards one's own occupation.
      LIMITATIONS: The patient group was selected from the practice of only one
      psychiatrist. CONCLUSIONS: Several psychosocial factors in childhood, female
      gender, social isolation and a negative attitude towards one's own occupation
      have previously been shown to be associated with the risk of depression. The
      results in this study suggest that these factors are also important in predicting
      the outcome of a major depressive episode and the risk of recurrent episodes.

PMID- 11511411
TI  - Melatonin response to clonidine administration in depression: indication of
      presynaptic alpha2-adrenoceptor dysfunction.
AB  - BACKGROUND: The aim of this study was to investigate alpha2-adrenoceptor
      sensitivity in depression, by using melatonin response to clonidine
      administration as an index of alpha2-adrenoceptor functioning. METHOD: 35
      depressed subjects and 41 healthy controls were assessed for overnight urinary
      melatonin pre- and post-administration of oral clonidine. RESULTS: Administration
      of clonidine significantly reduced melatonin concentrations in depressed patients
      but not in control subjects. LIMITATION: A single oral dose (0.15 mg) of
      clonidine was administered. CONCLUSIONS: Further indication is provided for
      presynaptic alpha2-adrenoceptor dysfunction in depression with the application of
      an alternative pharmacological challenge method.

PMID- 11511412
TI  - Carbamazepine treatment of corticosteroid-induced mood disorder.

PMID- 11511413
TI  - Drug-resistant Trypanosoma congolense in naturally infected donkeys in north Omo
      Zone, southern Ethiopia.
AB  - A three-part study was conducted to determine the efficacy of isometamidium
      chloride in donkey populations naturally infected with trypanosomes in north Omo
      Zone, southern Ethiopia. In the first, 373 randomly selected donkeys from four
      villages were examined for trypanosome infections by the dark ground/phase
      contrast buffy coat technique (BCT) in November 1999. The trypanosome prevalence
      was 18.2% (95% confidence interval (CI): 14.4, 22.5) and Trypanosoma congolense
      was the most common species accounting for 66.2% of the overall infections. In
      the second part, 40 infected donkeys were selected and treated with a
      prophylactic dose of 1.0mg/kg of isometamidium chloride and thereafter monitored
      every 14 days for 90 days. Trypanosomes were detected in eight donkeys within 1
      month and in 20 donkeys within 2 months of treatment. About 16% (5/32) of donkeys
      infected with T. congolense were detected parasitemic 1 month after treatment. In
      addition, the result also revealed that all relapse/breakthrough infections were
      due to T. congolense. In the third part of this study mice were infected with two
      T. congolense field isolates from donkeys that were found to be parasitemic
      within 1 or 2 months after isometamidium treatment. The mice were treated with
      ranges of doses of isometamidium chloride or diminazene aceturate and thereafter
      followed for relapse infection. Isometamidium chloride at doses 0.5-4 mg/kg body
      weight and diminazene aceturate at doses of 3.5-28 mg/kg body weight failed
      completely to cure T. congolense infections in any of the mice.

PMID- 11511414
TI  - Detection of haemoparasites in cattle by reverse line blot hybridisation with a
      note on the distribution of ticks in Sicily.
AB  - A reverse line blot hybridisation (RLB) of 21 oligonucleotides with polymerase
      chain reaction (PCR) amplified regions of 16S rRNA (Ehrlichia/Anaplasma group) or
      18S rRNA (Babesia/Theileria group) genes of haemoparasites detected Theileria
      annulata, T. buffeli/orientalis, Babesia bovis, B. bigemina, B. divergens,
      Ehrlichia bovis, Anaplasma marginale, A. centrale and unknown species within the
      Rickettsia tribe.A very high prevalence of mixed infections was detected, which
      indicated that animals infected with Babesia spp. were also infected with
      Theileria spp. and/or Anaplasma spp. The tick distribution appeared to be
      seasonal with Hyalomma marginatum as the most frequently observed tick and
      Boophilus annulatus and Ixodes ricinus as the least frequently observed ticks.
      Other species identified in the 818 ticks collected during the five sampling
      periods between April 1998 and November 1999 included H. lusitanicum,
      Rhipicephalus sanguineus group, R. bursa, Dermacentor marginatus, Haemaphysalis
      punctata, B. annulatus and I. ricinus.

PMID- 11511415
TI  - Trail antigen in Eimeria stiedai sporozoites associated with a thrombospondin
      related motif and the entry of cultured cells.
AB  - In order to examine the antigenic similarity and specificity of the trail antigen
      of Eimeria stiedai and Etp 100, a microneme protein of Eimeria tenella,
      monoclonal antibodies to the trail antigen of E. stiedai sporozoites were
      selected by an indirect immunofluorescent antibody method. The monoclonal
      antibody of one clone, 3D10, reacted with the anterior portion of non-fixed
      sporozoites. By immunoblotting, the monoclonal antibody was found to react with a
      100 kDa antigen of E. stiedai sporozoites, and a 117 kDa antigen of E. tenella
      sporozoites and merozoites. It was also found to react with a recombinant protein
      with thrombospondin-/properdin-like motifs homologous to E. tenella microneme
      protein Etp 100. The monoclonal antibody significantly inhibited the penetration
      of E. stiedai sporozoites into cultured rabbit hepatobiliary epithelial cells.
      These results suggest that E. stiedai sporozoites have a trail antigen, located
      in the anterior region on the outer surface of the sporozoites, which has an
      epitope with thrombospondin-/properdin-like motifs similar to E. tenella
      microneme protein Etp 100. This protein may play an important functional role in
      the process of penetration of host cells.

PMID- 11511416
TI  - Culicoides arakawae (Diptera: Ceratopogonidae) efficiently blood-fed and infected
      with Leucocytozoon caulleryi through a natural membrane.
AB  - Culicoides arakawae, the most common Culicoides sp. on chicken farms in East
      Asia, is an important blood-sucking insect and Leucocytozoon caulleryi vector.
      How parasites, in an ingested blood bolus, enter the midgut of insects and deal
      with this complex and biochemically hostile environment is poorly understood.
      However, successful blood-feeding through a membrane in C. arakawae is beneficial
      for studying this phenomenon. Therefore, a membrane-feeding method for C.
      arakawae was developed in. The blood-feeding success rates of C. arakawae fed
      through five different membranes were: turkey egg at 43.7+/-11.7%, chicken egg at
      45.2+/-12.1%, duck egg at 38.8+/-12.0%, pig gut at 0% and chick skin at 0%. In
      fertility measurements, the average number of eggs produced for C. arakawae fed
      through egg-shell membrane, at 77.7+/-15.1 per female, was significantly higher
      (P<0.01) than the 46.7+/-10.6 found in C. arakawae fed on the breast skin of a
      live chicken. Meanwhile, in parasite infectivity tests, C. arakawae could be
      infected by L. caulleryi when the vector was blood-fed with infective blood cells
      reconstituted with specific pathogen-free (SPF) sera through an egg-shell
      membrane. The sporozoite average and infection rates of inoculated chicks were
      166.8+/-12.5 and 100%, respectively. In conclusion, feeding C. arakawae blood
      through fowl-egg-shell membranes should be an efficient method for in vitro
      infection of midges as the engorged midges are infected by parasites and display
      reproductive potential. Furthermore, the method is practical for feeding a large
      number of midges.

PMID- 11511417
TI  - Hyalomma impeltatum (Acari: Ixodidae) as a potential vector of malignant
      theileriosis in sheep in Saudi Arabia.
AB  - Little is known about tick-borne diseases in Saudi Arabia, particularly regarding
      the prevalence of theileriosis in small ruminants. This survey studied the
      potential vectors of malignant theileriosis in Saudi Arabian sheep. Blood, lymph
      node and tick samples were collected from animals being treated or necropsied at
      the Veterinary Diagnostic Laboratory in Jeddah, Makkah (western region), and
      Bureida, Al-Qasim (central region). Blood and lymph node smears were prepared and
      examined for Theileria species. Theileria hirci (=T. lestoquardi) was found in
      lymph node smears of one out of 36 sheep (2.8%) in Jeddah and six of 25 sheep
      (24%) in Bureida. The erythrocytic forms were detected in 5-8% of RBCs. Ticks
      were found in relatively less number of sheep in Bureida and Jeddah, 17/180 and
      26/125, respectively. All Theileria-infected sheep were infested with Hyalomma
      impeltatum except the one that carried Hyalomma anatolicum anatolicum. This
      suggests that H. impeltatum is a potential vector of malignant theileriosis in
      Saudi Arabia.

PMID- 11511418
TI  - Nematocidal activities of thiabendazole and ivermectin against the larvae of
      Strongyloides ratti and S. venezuelensis.
AB  - With the aim of developing therapeutic agents for strongyloidosis, the disease
      caused by infection with Strongyloides stercoralis, we established a novel assay
      technique using S. ratti and S. venezuelensis as models for S. stercoralis. The
      newly developed assay technique was found to more accurately represent treatment
      induced larval paralysis than existing assays. Our method uses paper disks
      impregnated with the test solution, which even allows materials that are
      sparingly soluble in water to be tested. An inverted microscope was used to
      observe the larval states, and these states were recorded using a digital camera.
      We observed the activities of ivermectin and thiabendazole against larvae and
      calculated larval motility and velocity. These two factors were then combined to
      determine the overall viability of larvae at selected concentrations. The
      activities of the anthelmintics were compared by calculating the concentrations
      at which 50% viability was demonstrated, or in other words, the concentration at
      which paralysis was caused in 50% of the individuals (50% paralysis
      concentration; PC(50)). Evaluations after 24h of exposure yielded the following
      reproducible PC(50) values for ivermectin and thiabendazole, respectively: S.
      ratti, 2.4 and 140 microM; and S. venezuelensis, 2.3 and 190 microM. After
      treatment with ivermectin, there was a tendency for larval motility to be greater
      than that of the controls at low concentrations, a result that might be
      associated with its mechanism of action.

PMID- 11511419
TI  - Preventing transmission of Sarcoptes scabiei var. suis from infested sows to
      nursing piglets by a prefarrowing treatment with doramectin injectable solution.
AB  - Studies were conducted at swine facilities in Illinois and North Carolina to
      evaluate the effect of treatment with doramectin injectable solution on
      transmission prevention of Sarcoptes scabiei var. suis from sows to nursing
      piglets. Approximately 42 days prefarrowing, 58 mange-free sows were
      experimentally infested with 200 S. scabiei in each ear. Seven to fourteen days
      prior to farrowing, 22 sows were given doramectin injectable intramuscularly at a
      dose of 300 microg/kg of body weight. A total of 21 sows served as untreated
      controls. Skin scrapings for mite counts and lesion scoring were performed on
      sows before treatment on day 21, and on either day 35 or 42. Each sow was
      observed on days 0, 7, 14, 21, 28, and 35 or 42 for the incidence of
      scratching/rubbing. Skin scrapings, lesion scoring, and observation of
      scratching/rubbing were performed on the piglets after weaning and at the end of
      the nursery stage. Geometric mean mite counts of the untreated sows were 0.70 and
      0.26 on days 21 and 35 or 42, respectively, and 0.00 for doramectin-treated sows
      over the same time periods (P<0.05). Lesions scores and the incidence of
      scratching/rubbing were both higher in the untreated sows as compared to the
      doramectin-treated sows during the same time periods (P<0.05). Geometric mean
      mite counts of piglets farrowed by untreated sows were 0.50 and 0.60 after
      weaning and at the end of the nursery stage, respectively, and 0.00 for piglets
      from doramectin-treated sows over the same time periods (P>0.05). Lesion scores
      and the incidence of scratching/rubbing were both higher in piglets from
      untreated sows as compared to those piglets from doramectin-treated sows
      (P<0.05). Treating S. scabiei-infested sows with doramectin injectable solution
      before farrowing eliminated mite infestation and prevented the transmission of S.
      scabiei to piglets.

PMID- 11511420
TI  - Seroprevalence of Neospora caninum in female water buffaloes (Bubalus bubalis)
      from the southeastern region of Brazil.
AB  - Antibodies to Neospora caninum were assayed in sera of 222 female water buffaloes
      from Ribeira Valley of Sao Paulo State, Brazil, using an indirect fluorescent
      antibody test (IFAT) and Neospora agglutination test (NAT). IFAT antibodies were
      found in 64% of buffaloes with titers of 1:25 (42 buffaloes), 1:50 (53
      buffaloes), 1:100 (31 buffaloes), 1:200 (10 buffaloes), 1:400 (3 buffaloes), or >
      or =1:800 (3 buffaloes). NAT antibodies were found in 53% of buffaloes; in titers
      of 1:40 in 52 buffaloes, 1:80 in 27 buffaloes, 1:160 in 21 buffaloes, and > or
      =1:320 in 17 buffaloes. Results indicate a high prevalence of N. caninum exposure
      in water buffaloes in Brazil and warrant an investigation of the role of N.
      caninum as an abortifacient in water buffaloes.

PMID- 11511421
TI  - Molecular survey of Ehrlichia infection in ticks from animals in Yamaguchi
      Prefecture, Japan.
AB  - A total of 82 ticks collected from wild animals and dogs in Yamaguchi Prefecture,
      Japan were examined for Ehrlichia infection by using polymerase chain reaction
      (PCR) primers that amplify DNA of most members of the genus Ehrlichia. A DNA
      sample from an Ixodes ovatus nymph from a bear in Yamaguchi Prefecture, Japan,
      was positive in the screening PCR. Subsequent PCR using two sets of primers
      yielded a 1431 bp segment of the 16S rRNA gene and the sequence was very similar
      to those of E. chaffeensis and E. muris, and a strain variant of a recently
      described Ehrlichia species isolated from I. ovatus in other prefectures of
      Japan.

PMID- 11511422
TI  - The value of natriuretic peptides for the management of heart failure: current
      state of play.

PMID- 11511423
TI  - Pharmacoeconomics of beta-blockers: effective and cost-effective therapy in
      chronic heart failure.

PMID- 11511424
TI  - Cardiomyoplasty for treatment of heart failure.

PMID- 11511425
TI  - Up-regulation of 'clearance' receptors in patients with chronic heart failure: a
      possible explanation for the resistance to biological effects of cardiac
      natriuretic hormones.
AB  - BACKGROUND: Three specific receptors for the cardiac natriuretic peptide system
      have been identified to date. Down-regulation of the biologically active binding
      sites (i.e. NPR-A and NPR-B) could explain the blunted response to cardiac
      natriuretic hormones observed in heart failure (HF), but not the increased
      metabolic clearance rate. Variations in the ratio between biological and
      clearance (NPR-C) receptors in target tissue may explain this increase. AIM: The
      aim of this study was to investigate the regulation of NPR-C receptors on
      platelets, in patients with HF. METHODS: Eighteen patients with HF (NYHA class: I
      II, n=8; III-IV, n=10) and 18 age-matched healthy subjects were studied. The
      affinity constant (K(d)) and density (B(max)) of binding sites were derived by
      saturation assays on platelet suspensions using 125I-ANP as radioligand. RESULTS:
      B(max) increased as a function of the severity of disease: 21.3+/-3.3 fmol/10(9)
      cells in class III-IV, 11.7+/-2.2 in class I-II, and 11.6+/-1.1 in controls,
      respectively (P=0.0179 for class III-IV vs. controls and P=0.0451 vs. NYHA I-II).
      CONCLUSIONS: The increase in density of 'clearance' receptors in severe HF is
      theoretically consistent with the reduction in cardiac natriuretic peptide
      biological activity, as well as the increase in metabolic clearance rate. This
      suggests that clearance receptor blockade may be of potential therapeutic value
      in HF.

PMID- 11511426
TI  - Activation of the cardiac interleukin-6 system in advanced heart failure.
AB  - OBJECTIVES: The study objective was to assess the cardiac expression of
      interleukin-6 (IL6) and its receptor (IL6R) in advanced heart failure.
      BACKGROUND: While IL6 plasma levels are elevated and associated with an impaired
      prognosis in advanced heart failure, little is known about the intracardiac
      expression of the IL6 system. METHODS: Heart tissue was obtained from 20 patients
      (n=10, idiopathic dilated cardiomyopathy, age 44+/-15 years; n=10, ischemic
      cardiomyopathy, age 55+/-8 years) at the time of transplantation. Left and right
      ventricular tissue was subjected to in situ hybridization, Northern blot
      analysis, and RT-PCR. Signals were quantified by densitometric scanning and
      corrected for G3PDH-mRNA levels. Right ventricular biopsy specimens (n=11) of
      patients with arrhythmias and normal cardiac function served as controls. In
      addition, data were correlated with cardiac catheterization and echocardiography
      data obtained at transplant evaluation. RESULTS: Ventricular IL6 and IL6R
      transcripts were detected in all explant specimens examined. Expression of both
      mRNA species was higher than in controls (P=0.001). Left ventricular IL6 mRNA
      levels correlated positively with heart rate (r=0.77; P=0.009), pulmonary
      capillary wedge pressure (r=0.53; P=0.03), right atrial pressure (r=0.77;
      P=0.003), and inversely with left ventricular ejection fraction (r=-0.61;
      P=0.03). Right ventricular IL6 mRNA levels correlated inversely with cardiac
      index (r=-0.48; P=0.05). IL6R expression did not correlate with hemodynamic data.
      CONCLUSIONS: In advanced heart failure, cardiac IL6/IL6R mRNA expression is
      increased and may play a role in the pathophysiology of advanced heart failure.

PMID- 11511427
TI  - Breath isoprene in patients with heart failure.
AB  - BACKGROUND: Chronic heart failure (CHF) is characterised by increased vascular
      resistance. This increased after load on the left ventricle contributes to the
      vicious cycle that leads to progression of myocardial failure, multiple organ
      failure and death. There is evidence for increased oxidative stress in heart
      failure, which will influence the myocardium but also peripheral vasculature
      endothelium. AIMS: The aim of the present study was to examine the production of
      isoprene, reputed to reflect oxidative stress, in patients with CHF compared to
      control subjects. METHODS: Twelve patients with CHF and thirty-one healthy
      control subjects free from heart disease were studied. Breath was collected via a
      two-way non-re-breathing valve into a 60-l gas collection bag. A sample of
      ambient air was collected at the same time. A measured aliquot of patient breath
      and ambient air (approx. 1.5 l) was adsorbed onto a gas adsorption tube packed
      with poropak-Q. Isoprene was measured using GC/MS and the production rate
      calculated. All samples of breath were collected at 10.00 h after subjects had
      been sitting at rest for 15 min. RESULTS: Breath isoprene production in subjects
      with CHF was significantly reduced compared to controls 83(23) vs. 168(20) pmol
      min(-1) kg(-1). CONCLUSION: Breath isoprene does not directly reflect oxidative
      stress in CHF.

PMID- 11511428
TI  - Abnormal contractile responses during dobutamine stress echocardiography in
      patients with idiopathic dilated cardiomyopathy.
AB  - BACKGROUND: In chronic heart failure augmented wall stress leads to increased
      energy demand. Supply, however, may be reduced due to coronary vasoconstriction
      and endothelial dysfunction. This might lead to a mismatch between demand and
      supply. In the present study we further explored the effect of increased demand
      during dobutamine stress echocardiography. METHODS AND RESULTS: Sixteen patients
      with idiopathic dilated cardiomyopathy (mean age 44+/-13 years, New York Heart
      Association class II-III, mean left ventricular ejection fraction 0.27+/-0.10)
      underwent dobutamine stress echocardiography (5-40 microg/min per kg
      bodyweight+atropine if required). Wall motion and thickening was assessed in 16
      segments using a four-point scale. Eleven patients (69%) showed regions with
      worsening of wall motion or a biphasic response during dobutamine infusion. Of
      the remaining five patients one patient did not show any wall motion changes and
      one patient showed a partial improvement while only in three patients wall motion
      improvement in the whole heart was found. CONCLUSION: A majority of patients with
      idiopathic dilated cardiomyopathy showed decreased wall motion during increased
      demand, i.e. ischemia-like myocardial contractile responses during dobutamine
      stress echocardiography. These findings further support the concept that an
      energy mismatch between demand and supply might play a pathophysiological role in
      idiopathic dilated cardiomyopathy.

PMID- 11511429
TI  - Beneficial effect of carvedilol on heart rate response to exercise in digitalised
      patients with heart failure in atrial fibrillation due to idiopathic dilated
      cardiomyopathy.
AB  - Fourteen digitalised patients diagnosed with heart failure (NYHA Functional class
      II) with idiopathic dilated cardiomyopathy in chronic established atrial
      fibrillation were administered carvedilol in addition to their anti-heart failure
      medications in an attempt to improve their heart rate control. Fourteen matched
      patients who did not receive carvedilol acted as control subjects. Patients
      treated with carvedilol showed significantly reduced resting heart rates (10
      36%), maximal heart rates on exercise (5-20%) and an increased exercise time (2
      30%) on treadmill stress tests (all P=0.001). Ventricular ectopic activity was
      also diminished. This was associated with symptomatic improvement in effort
      intolerance and palpitations. NYHA functional class, left ventricular dimensions
      and ejection fractions did not improve during the study period of 3 months. Thus,
      addition of carvedilol to digoxin had a beneficial effect on exercise tolerance
      in patients with idiopathic dilated cardiomyopathy in atrial fibrillation by
      virtue of an improved heart rate control both at rest and on exercise. Carvedilol
      was well tolerated despite impaired myocardial function.

PMID- 11511430
TI  - Evaluation of left ventricular function and mitral regurgitation during left
      ventricular-based pacing in patients with heart failure.
AB  - BACKGROUND: Beneficial effects of left ventricular (LV)-based pacing on acute
      hemodynamic parameters were reported in several series, but only a few studies
      examined the long-term effects of this new pacing procedure. AIMS: To assess long
      term effects of permanent LV-based pacing on LV function and mitral regurgitation
      (MR) in patients with refractory congestive heart failure (CHF). METHODS: A
      prospective evaluation of LV function and MR was performed in 23 patients with
      severe but stable CHF and left bundle branch block (mean QRS: 186+/-31 ms) by
      radionuclide and echocardiographic techniques at baseline and 6 months after
      implantation of a permanent LV-based (LV alone: 13 patients; biventricular: 10
      patients) pacemaker programmed either in a DDD mode (sinus rhythm; n=14) or in a
      VVIR mode (atrial fibrillation; n=9). RESULTS: Compared to baseline, the 6 months
      follow-up visit demonstrated a significant increase in radionuclide derived LV
      ejection fraction from 23.3+/-7 to 26.2+/-7% (P<0.01) and in echocardiographic LV
      fractional shortening from 13+/-4 to 16+/-6% (P<0.05), without any change in
      cardiac index, a significant decrease in LV end-diastolic diameter (from 73.2+/-6
      to 71.2+/-7 mm; P<0.05), end-systolic diameter (from 63.6+/-6 to 60.2+/-8 mm;
      P<0.05) and color Doppler MR jet area (from 11.5+/-6 to 6.6+/-4 cm(1); P<0.001).
      A comparison of patients with LV pacing alone and patients with biventricular
      pacing showed similar beneficial effects of pacing on MR severity in the two
      subgroups and a non-significant trend for a better improvement of LV function
      during biventricular pacing. CONCLUSION: Thus, in patients with severe CHF and
      left bundle branch block, permanent LV-based pacing may significantly improve LV
      systolic function and decrease MR.

PMID- 11511431
TI  - Malnutrition in patients suffering from chronic heart failure; the nurse's care.
AB  - Chronic heart failure is associated with a bad prognosis with considerably
      shortened survival and repeated hospitalisations. Patients suffering from heart
      failure also have symptoms that can affect their food intake, for example,
      tiredness when strained, breathing difficulties and gastrointestinal symptoms
      like nausea, loss of appetite and ascites. Pharmacological therapy can lead to a
      loss of appetite, which will make the intake of food inadequate to fill the
      required energy and nutritional needs. The nurse's interest in and knowledge of
      diet issues can improve these patients' nutritional status. The aim of this
      literature review was to describe the nurse's interventions regarding
      malnutrition in patients suffering from chronic heart failure. The literature
      search gave 13 articles, which were analysed, and sentences whose content was
      related to the aim were identified. Three areas of content appeared; drug
      treatment and consequences, gastrointestinal effects, and information and
      education. The results show that the nutritional status of these patients can be
      significantly improved by means of simple nursing interventions. Future research
      should focus on controlled experimental studies to evaluate differences in body
      weight, body mass index and quality of life between patients suffering from
      chronic heart failure, who are taking part in a fully enriched nutrition
      intervention, and patients suffering from chronic heart failure, who are eating
      their normal diet.

PMID- 11511432
TI  - Tezosentan (an intravenous endothelin receptor A/B antagonist) reduces peripheral
      resistance and increases cardiac power therefore preventing a steep decrease in
      blood pressure in patients with congestive heart failure.
AB  - OBJECTIVE: This study investigated the effect of tezosentan (an intravenous
      endothelin-1 receptor antagonist) on vascular resistance and cardiac function and
      determined the dose response in patients with stable congestive heart failure
      (CHF) due to left ventricular systolic dysfunction. METHODS: In a double-blind
      fashion, tezosentan or placebo were administered in ascending doses (5, 20, 50,
      100 mg h(-1)) to 38 CHF (NYHA class III) patients with ejection fraction <or=35%,
      cardiac index <or=2.7 l min(-1) m(-2) and pulmonary capillary wedge pressure
      >or=15 mmHg. Systemic vascular resistance index (SVRi) was estimated as mean
      arterial blood pressure [(MAP-right atrial pressure)/cardiac index (CI)]. Cardiac
      function was assessed as cardiac power index (Cpi), calculated as pressure x flow
      (MAP x CI), where MAP represents pressure and CI represents cardiovascular flow.
      RESULTS AND DISCUSSION: Compared to the placebo, tezosentan induced a dose
      dependent decrease in SVRi (-32%), an increase in Cpi (+20%) and a small decrease
      in MAP (-9%). By contrast, patients treated with nitrate vasodilators or
      nesiritide (a natriuretic peptide) showed a decrease in SVRi not accompanied by a
      significant increase in Cpi leading to a steep decrease in MAP. CONCLUSIONS: The
      use of Cpi in the assessment of the hemodynamic effects of tezosentan, provides a
      useful alternative characterization of the complex influences of vasodilators on
      cardiac function in patients with CHF.

PMID- 11511433
TI  - Effect of metoprolol CR/XL on exercise tolerance in chronic heart failure - a
      substudy to the MERIT-HF trial.
AB  - BACKGROUND: Beta-blockade usually causes a slight reduction in exercise capacity
      among healthy subjects, while more variable results have been observed in chronic
      heart failure (CHF), probably related to patients studied, methods and agent
      used. The effect of metoprolol controlled release/extended release (CR/XL) on
      peak oxygen uptake (peak VO(2)) in this patient population has not previously
      been investigated. AIMS: We examined the effect of long-term treatment with the
      selective beta(1)-receptor blocker metoprolol CR/XL once daily on exercise
      capacity in patients with CHF. METHODS: Ninety-four patients (70 males and 24
      females; mean age 63.6+/-10.6 years) with chronic symptomatic heart failure in
      New York Heart Association (NYHA) functional class II-IV, and with ejection
      fraction <or=40%, stabilized on optimum standard therapy were randomized to
      metoprolol CR/XL or placebo in a double-blind trial. Exercise capacity was
      evaluated by peak VO(2) at baseline, after 3 months and at the end of study (mean
      follow-up 11.4+/-0.4 months). RESULTS: Compared with placebo metoprolol CR/XL
      produced a significant decrease in heart rate by 11 beats/min at rest and 18
      beats/min at peak exercise. There was a tendency for a temporal decline in peak
      VO(2) after 3 months of therapy in both groups, but altogether peak VO(2)
      remained unchanged from baseline with no difference between the groups at 1 year.
      CONCLUSIONS: In patients with moderate to severe CHF, 11.4 months of beta(1)
      blockade with metoprolol CR/XL had no effect on exercise capacity when compared
      with placebo or baseline.

PMID- 11511434
TI  - Results from post-hoc analyses of the CIBIS II trial: effect of bisoprolol in
      high-risk patient groups with chronic heart failure.
AB  - BACKGROUND: The beneficial effects of the beta-blocker bisoprolol on mortality
      and rate of hospitalisation as well as its safety in patients with chronic heart
      failure has been proven. However, its efficacy in patients in whom beta-blockers
      have traditionally been contraindicated or caution has been advised has not been
      clearly determined. Therefore, analyses in high-risk subgroups of patients taking
      part in CIBIS II have been performed to investigate the effect of bisoprolol in
      elderly patients, in patients with type 2 diabetes, with renal failure, NYHA
      functional class IV or concomitantly treated with digitalis, aldosterone
      antagonists or amiodarone. METHODS: High-risk subgroups of patients with chronic
      heart failure taking part in the CIBIS II study were retrospectively analysed
      with respect to mortality, hospitalisation, combined endpoint of cardiovascular
      mortality or hospitalisation for cardiovascular reasons and treatment withdrawal
      as well as cause of death and hospitalisation. Analysis is based on intention-to
      treat. RESULTS: It was demonstrated that in spite of the expected increase in the
      overall risk of death and hospitalisation, patients who are diabetic, have renal
      impairment, NYHA class IV symptoms, are elderly, are taking either digitalis,
      amiodarone or aldosterone antagonists as co-medication benefit equally from beta
      blockade with bisoprolol as patients without these complications or drugs.
      Benefit was shown for the primary endpoint all cause mortality, as well as for
      the secondary endpoints. CONCLUSIONS: Contrary to the hitherto prevailing
      doctrine of not using beta-blockers in high risk patient groups with chronic
      heart failure, retrospective analyses of the CIBIS II study justify the use of
      this drug class in patients regardless of age, NYHA functional class, the
      presence of diabetes, renal impairment or concomitant treatment with digitalis,
      amiodarone or aldosterone antagonists.

PMID- 11511435
TI  - The CARE-HF study (CArdiac REsynchronisation in Heart Failure study): rationale,
      design and end-points.
AB  - BACKGROUND: Cardiac resynchronisation is a promising new intervention for
      patients with heart failure, left ventricular systolic dysfunction and
      ventricular dyssynchrony. OBJECTIVE: The CARE-HF trial is designed to evaluate
      the long-term effects of cardiac (atrio-bi-ventricular) resynchronisation on the
      mortality and morbidity of patients with heart failure due to left ventricular
      systolic dysfunction already receiving diuretics and optimal medical therapy with
      ACE inhibitors and beta-blockers (where indicated and tolerated). METHODS AND
      RESULTS: Approximately 800 patients will be randomised to device therapy or
      control and followed for a minimum of 18 months. A pragmatic study design has
      been chosen that does not attempt to conceal allocation from investigators or
      patients because it is impossible to guarantee maintenance of blinding for the
      duration of the study. The end-points committee will adjudicate events in a
      blinded fashion. Since cardiac resynchronisation may alter other aspects of the
      management of the patient, as would occur in clinical practice, the study should
      be considered a comparison of strategies rather than simply of a device. The
      primary end-point is all-cause mortality or unplanned cardiovascular
      hospitalisation. The study should complete recruitment during 2002 and report in
      2004.

PMID- 11511436
TI  - Clinical trials update: Highlights of the Scientific Sessions of Heart Failure
      2001, a meeting of the Working Group on Heart Failure of the European Society of
      Cardiology. CONTAK-CD, CHRISTMAS, OPTIME-CHF.
AB  - This article continues a series of reports summarising recent research
      developments pertinent to the topic of heart failure. This is a summary of
      presentations made at Scientific Sessions of Heart Failure 2001, a meeting of the
      Working Group on Heart Failure of the European Society of Cardiology. Clinical
      studies of particular interest to people caring for patients with heart failure
      include CONTAK-CD, CHRISTMAS and further updates on OPTIME-CHF. A brief review of
      the current status of cardiac resynchronisation therapy is included.

PMID- 11511437
TI  - Practical recommendations for the use of ACE inhibitors, beta-blockers and
      spironolactone in heart failure: putting guidelines into practice.
AB  - Surveys of prescribing in both hospitals and primary care have shown delays in
      translating improved survival data from clinical trials into clinical practice
      thereby denying patients the benefits of proven treatments, such as the
      angiotensin converting enzyme inhibitors. This may be due to unfamiliarity with
      clinical guidelines and concerns about adverse events. Recent trials have shown
      that substantial improvements in survival are associated with spironolactone and
      beta-blocker therapy. In order to accelerate the uptake of these treatments, and
      to ensure that all eligible patients should receive the most appropriate
      medications, a clear and concise set of clinical recommendations has been
      prepared by a group of clinicians with practical expertise in the management of
      heart failure. The objective of these recommendations is to provide practical
      guidance for non-specialists in order to support the implementation of evidenced
      based therapy for heart failure. These practical recommendations are meant to
      supplement rather than replace existing guidelines.

PMID- 11511438
TI  - Ambulatory heart failure management in private practice in France.
AB  - Management of ambulatory heart failure was assessed in a group of 600 patients,
      mean age 73, 64% males, NYHA I: 9%; II: 52%; III: 33%; IV: 6%; followed up by a
      representative sample of private cardiologists. Fifty-two percent of patients had
      been previously hospitalised for worsening heart failure with a mean duration of
      stay of 13.1 days, for those hospitalised in the year preceding the survey (26%).
      First diagnosis of heart failure had been performed by a cardiologist (57%), a
      general practitioner (37%) or another category of physician (6%). Seventy percent
      of patients received three or more different classes of heart failure
      medications. Diuretics were prescribed to 71%, angiotensin converting enzyme
      inhibitors to 54% and digitalis to 35% of the population. Beta-blockers were
      given to only 14% of the patients. In patients aged over 80 years, only 45%
      received angiotensin converting enzyme inhibitors. CONCLUSION: This survey of
      ambulatory heart failure patients confirms that the disease is predominantly
      observed in elderly patients, and associated with prolonged and recurrent
      hospitalisations. The underuse of recommended therapeutic classes including
      angiotensin converting enzyme inhibitors and beta-blockers deserves further
      investigation.

PMID- 11511439
TI  - Management of heart failure in Belgium.

PMID- 11511440
TI  - Eating right revised. The new American Heart Association dietary guidelines.

PMID- 11511441
TI  - Abdominal aortic aneurysms: when should surgery be performed?

PMID- 11511442
TI  - Heart lines. Hormone-replacement therapy and stroke risk.

PMID- 11511443
TI  - Heart lines. Can statins help prevent diabetes?

PMID- 11511444
TI  - Ask the doctor. My cholesterol profile is pretty good, except that my HDL level
      is only 32 mg/dL, and I know the normal range is 40 or more. My LDL cholesterol
      is 110 mg/dL and my triglycerides are in the normal range. I don't have a history
      of heart disease and I've never had any symptoms (or diagnosis) of heart disease.
      Should I be taking a drug to raise my HDL?

PMID- 11511445
TI  - Ask the doctor. A few years ago, I had a heart attack. My doctor treated me with
      angioplasty, and I haven't had any symptoms of heart disease since. I do carry a
      bottle nitroglycerin with me, but haven't taken any in years. I renew my
      prescription every six months because I know the pills go bad. My problem is that
      I also need Viagra to have sexual intercourse. Whenever I refill my prescription
      for Viagra, the pharmacist gives me a hard time because he knows I also have a
      prescription for nitroglycerin. Just how dangerous is Viagra?

PMID- 11511446
TI  - Ask the doctor. A few months ago, I was diagnosed with atrial fibrillation. My
      doctor put me on blood thinners for a few weeks and then performed electrical
      cardioversion. Naturally, I was asleep during the procedure, but I understand
      that they shocked me twice and both times my heart briefly returned to a normal
      rhythm. But after a few seconds it went back into atrial fibrillation. NOw my
      doctor has offered me a choice. I can stay in atrial fibrillation and take a
      blood thinner for the rest of my life. Or I can try a medication to restore a
      normal heart rhythm and give cardioversion another try (but I'll probably have to
      take the antiarrhythmia drug for a long time). Any suggestions?

PMID- 11511447
TI  - Cancer treatment. New drugs, new hope.

PMID- 11511448
TI  - Emergency medicine. When should you go to the emergency room?

PMID- 11511449
TI  - Pain medicine. The dangers of acetaminophen.

PMID- 11511450
TI  - Health beat. Cholesterol. I. Highlights of the new guidelines.

PMID- 11511451
TI  - Health beat. Cholesterol. II. Eggs reconsidered. again.

PMID- 11511452
TI  - By the way, doctor... My neighbor takes something called milk thistle. He likes
      to drink alcohol and believes the herb will protect him against any kind of liver
      damage. Is he right?

PMID- 11511453
TI  - By the way, doctor... I like my doctor, but I can't help but notice that he
      doesn't seem to wash his hands before or after he examines me. Should I say
      something to him?

PMID- 11511454
TI  - By the way, doctor... My father's memory has gotten a lot worse over the past
      year, but he doesn't seem to be aware of it. When I visited him recently, I saw
      what looked like some bad sores on his legs. He told me that he'd gone to the
      doctor recently and that everything was fine. Would it be wrong for me to call
      his doctor to find out for sure?

PMID- 11511455
TI  - Autism -- Part II.

PMID- 11511456
TI  - Firearms and suicide.

PMID- 11511458
TI  - Prozac weekly.

PMID- 11511457
TI  - MDMA.

PMID- 11511459
TI  - The PSA: one test with three uses.

PMID- 11511460
TI  - Macular degeneration: looking age in the eye.

PMID- 11511461
TI  - Medical memo. The stroke unit arrives.

PMID- 11511462
TI  - On call. I'm a 76-year-old man with an enlarged prostate. I've been taking
      Cardura and it's helped a lot, but my doctor stopped it because he said a study
      found the drug could cause heart failure. Now I'm getting up three or four times
      a night again. Is Cadura safe?

PMID- 11511463
TI  - Second that opinion.

PMID- 11511465
TI  - Dental implant update.

PMID- 11511464
TI  - New drug builds bone.

PMID- 11511466
TI  - Type 2 diabetes in women.

PMID- 11511467
TI  - Physical activity, Part II. Exercise: a good health prescription.

PMID- 11511468
TI  - By the way, doctor. I've been taking Prempro as a hormone replacement of six
      years and have decided to taper off. My doctor has cut my estrogen dose in half.
      Should my dose of progesterone be reduced as well?

PMID- 11511469
TI  - By the way, doctor. I received a widely circulated e-mail message about use of
      the CA-125 blood test in screening for ovarian cancer. The message suggested that
      the CA-125 test be used for routine screening, like a Pap smear. Do you agree?
      What's your opinion of this test?

PMID- 11511470
TI  - Small nasal defects.
AB  - The nose occupies an important feature of a person's central face. The size,
      shape, and proportions of the various characteristics of the face provide a
      visual basis suggesting the character of the person. Scars, asymmetries, and any
      abnormalities of the central face are easily recognizable and noted by even a
      casual observer. Over the centuries, therefore, much attention has been paid to
      reconstruction of facial and nasal abnormalities of both acquired and congenital
      etiologies. The purpose of this article is to address the reconstruction of
      smaller defects of the nose, encompassing surface areas of 1.5 to 2 centimeters.

PMID- 11511471
TI  - Reconstruction of large nasal defects.
AB  - Large nasal defects resulting from trauma or oncologic resection are a difficult
      reconstructive challenge, requiring special structural and aesthetic
      considerations. This article reviews reconstructive options by anatomic site and
      discusses techniques that address more complex defects, such as those involving
      multiple aesthetic units.

PMID- 11511472
TI  - Auricular reconstruction.
AB  - Auricular defects occur from a variety of different causes and a wide array of
      reconstructive options are often necessary. This article presents a general
      algorithm for approaching the reconstruction of auricular defects. The spectrum
      of problems ranges from simple lacerations to superficial cutaneous defects to
      total avulsions. There are small tips that can help improve results with adjacent
      flaps as well as guidelines for total auricular reconstruction.

PMID- 11511473
TI  - Complications, salvage, and enhancement of local flaps in facial reconstruction.
AB  - Complications are part of every surgical procedure and their occurrences are
      inevitable if the surgeon performs enough operations during his/her lifetime.
      Learning how to prevent complications and how to manage them when they occur are
      as important as learning how to perform any given surgical procedure. This is
      especially true in facial reconstruction with local flaps, as complications
      threaten not only the functional restoration of the integrity, but also the
      cosmetic appearance of the patient. This article describes common complications
      and their underlying mechanisms seen in facial reconstruction with local flaps as
      well as their treatment or prevention, when possible.

PMID- 11511474
TI  - Applications of hyperbaric oxygen in otolaryngology head and neck surgery: facial
      cutaneous flaps.
AB  - Hyperbaric oxygen therapy is of significant benefit in the setting of an ischemic
      flap of the head and neck. Mechanistically, hyperbaric oxygen decreases local
      tissue edema and improves oxygen delivery to compromised tissues. Both capillary
      and fibroblast in-growth occur at a greater rate with hyperbaric oxygen therapy,
      and there is an increase in the tensile strength of the wound. Additional
      indications in the head and neck include traumatic composite amputations,
      necrotizing soft-tissue infections, and osteoradionecrosis of the facial
      skeleton.

PMID- 11511475
TI  - Scar revision.
AB  - Individuals bearing scars deemed functionally or cosmetically undesirable often
      seek the services of a surgeon to eliminate the scars and to restore the tissue
      to its preinjury state. The foremost task of the physician is to inform the
      patient that elimination of scars is almost impossible, but that improvement is
      realistic. It should be stressed to the patient that scar revision replaces one
      scar for another in an attempt to improve the acceptability of that scar. A
      patient with realistic expectations is more likely to be a satisfied patient.
      This article examines the nature of scars and scar revision and the different
      surgical techniques available.

PMID- 11511479
TI  - Alternatives to hospital care for older people.

PMID- 11511480
TI  - Older people in accident and emergency departments.
AB  - Older people attend accident and emergency departments more frequently than
      younger people. However, most assessments indicate that this higher level of use
      is appropriate and is the result of more serious injury and illness among this
      population. Older patients discharged from accident and emergency departments are
      frequently functionally impaired with serious impacts upon their ability to
      perform activities of daily living. Despite this, relatively little attention has
      been paid to interventions to improve older patients' ability to self-care after
      discharge from accident and emergency departments. One study has suggested that
      dependency can be reduced by health visitor intervention. Targeted bi
      disciplinary interventions have been demonstrated to reduce the risk of recurrent
      falls in elderly patients discharged from accident and emergency departments.

PMID- 11511481
TI  - Community hospitals and older people.
AB  - Recent health care policy has promoted the community hospital as one remedy for
      the contracted district general hospital. Unfortunately, a literature review
      reveals a weak evidence-base to support this policy. Although descriptive studies
      demonstrate the flexible, multi-purpose role of community hospitals, there is a
      worrying paucity of clinical outcome studies and no robust health economic
      evaluation. An important potential role for community hospitals is in the post
      acute care of older people. However, evaluation by randomized trial is required
      to demonstrate effectiveness and cost effectiveness of community hospital
      transfer compared to alternatives such as remaining in a district general
      hospital.

PMID- 11511482
TI  - Hospital-at-home.
AB  - Hospital-at-home schemes are becoming an increasingly popular way of delivering
      health care world-wide. Schemes differ in the type of patients they cater for and
      in the intensity and complexity of treatment they provide. Although they have
      been in existence since 1961, there have been few randomized controlled studies
      to determine their effectiveness as an alternative to standard hospital care.
      Furthermore, some studies have produced conflicting results. Although there is
      accumulating evidence that they produce satisfactory patient outcomes and are
      acceptable to patients and carers, their cost-effectiveness is still uncertain.
      Further randomized controlled studies incorporating prospective cost analyses are
      needed. This paper discusses the evidence to support hospital-at-home as an
      alternative and complementary model of health care particularly for older people.

PMID- 11511483
TI  - Governance and autonomy in alternatives to hospital care.
AB  - Older people with complex illness and disability should have the same equitable
      opportunities and safeguards for treatment and care as do younger people. These
      should be based on needs, likely health gain and personal preference.
      Comprehensive assessment and goal setting, with monitoring of progress and
      outcomes, should be an integral feature of alternatives to hospital care,
      wherever they are provided. To satisfy the principles of clinical governance the
      development of innovative intermediate rehabilitative and long-term care
      programmes may require more time and expertise than small purchasing groups can
      reasonably provide. Pooled health and care budgets managed in partnership by
      larger providers may offer a solution. There is an urgent need for pilot projects
      to inform development.

PMID- 11511484
TI  - Intermediate care--a challenge to specialty of geriatric medicine or its
      renaissance?
AB  - The specialism of geriatric medicine has developed considerably in the last half
      of the twentieth century. In Great Britain it has emerged from its sombre
      beginnings in Victorian poor law institutions to become one of the largest
      specialities in medicine encompassing a wide range of disciplines and interests.
      More recently, there has been a parallel development in "intermediate care" a
      sweeping phrase that encompasses a wide diversity of practices in a plethora of
      venues. Although there is considerable attraction in minimising the duration of
      hospital stay by older people, there is a real risk of intermediate care being
      used as a euphemism for indeterminate neglect. For older people to benefit from
      appropriate treatment and care, the lessons learnt by earlier generations of
      geriatricians, and supported by the international evidence base should not be
      disregarded. Elderly people need a full multi-disciplinary assessment
      (comprehensive geriatric assessment) and continued involvement of skilled and
      trained personnel in their continuing care (geriatric evaluation and management).
      The recommendations of the British Geriatrics Society on intermediate care are
      commended and should be adhered to by all planners and providers of intermediate
      care. There is considerable logic in developing ways in which the two
      developments can be integrated to build upon the best features of both.

PMID- 11511485
TI  - Nursing homes: a suitable alternative to hospital care for older people in the
      UK?
AB  - Over the past two decades nursing homes have become the major supplier of long
      stay care for frail older people in the UK. Demographic projections indicate that
      the volume of nursing home places will continue to increase to keep pace with
      demand and that the population of homes will become steadily more dependent.
      Little systematic research exists to indicate how nursing home care compares with
      hospital care; the evidence that does exists tends to be restricted to local
      studies and thus is not generalizable. Local studies indicate that in both care
      settings there are shortfalls in terms of meeting basic quality of care
      standards. Despite this, there is obvious potential for nursing homes to act as
      an alternative to hospitalization, provided that there is suitable access for
      residents to specialist care and, for example, appropriate administration of
      medicines. Proposed changes in government policy will introduce more uniform
      standards in nursing homes and associated inspection structures and procedures.
      However, further research is needed to ascertain the clinical and consumer value
      of different interventions in nursing homes, and the cost-benefit of enhancing
      provision available in terms of preventing or forestalling demand on hospitals or
      reducing hospital length of stay. In the light of the commitment to develop
      evidence based practice, it is important that such research is urgently advanced
      to eliminate poor practice. In our rights conscious society, future generations
      of older people are unlikely to be as tolerant of substandard care.

PMID- 11511486
TI  - Intermediate care--a good thing?
AB  - In this paper, the intermediate care concept will be developed, and a new
      definition proposed. The evidence on effectiveness will be summarised, focusing
      on comprehensive geriatric assessment, admission avoidance, nurse-led units for
      post-acute care, and supported early discharge arrangements. It is a working
      premise of the paper that, in principle, intermediate care is not only a "good"
      but also a necessary "thing". However, with the exception of comprehensive
      assessment, the evidence for many services that fall under the broad rubric of
      intermediate care is lacking, inconclusive or negative. The implications of this
      for both practice and research will be discussed.

PMID- 11511488
TI  - A primary care perspective.

PMID- 11511487
TI  - Community outreach rehabilitation.
AB  - OBJECTIVE: to review controlled studies evaluating the effectiveness of community
      rehabilitation schemes developed to facilitate effective discharge from hospital.
      To briefly describe the community outreach rehabilitation scheme which has been
      developed in York, UK. RESULTS: in the last 10 years, 9 controlled trials were
      identified of which 6 resulted in improved outcome. There were no overall or
      mixed outcome differences observed in the other 3. Cost analysis calculations
      were controversial. However, in 4 of the studies early structured discharge
      appeared to result in cost savings-mainly by reducing hospital length of stay.
      CONCLUSION: though the studies were heterogeneous in design and involved
      different patient groups, community rehabilitation schemes appeared to be
      effective in facilitating earlier discharge from hospital.

PMID- 11511489
TI  - In the eyes of the beholder: what we see is not what we get.

PMID- 11511490
TI  - Depleted uranium and radiation-induced lung cancer and leukaemia.

PMID- 11511491
TI  - Maximizing the benefit--minimizing the risk: the developing role of radiographers
      in performing intravenous injections.
AB  - Performance of intravenous (iv) injections as part of radiographer role
      development has become fundamental to the operational management of diagnostic
      imaging departments in the UK. Through discussion of appropriate areas, this
      review aims to highlight current issues pertaining to iv injection. More
      importantly, the framework described could be transposed to other existing or
      future areas of role development. Within a validated system of delegation,
      utilization of radiographers' skills in an expanded role improves allocation of
      resources and may increase radiographer motivation and provide career
      enhancement. Professional body accreditation as well as civil and employment law
      provide clear guidelines on medicolegal implications, valid consent and
      accountability. Implementation of an iv administration policy, based on Royal
      College of Radiologists guidelines, includes proper delegation of duties and safe
      administration of substances. This should help ensure acceptance of vicarious
      liability by an employer. Failure to adhere to these established guidelines could
      leave employers and radiographers vulnerable to medicolegal action. Furthermore,
      evaluation of radiographer performance, facilitated by clinical governance and
      departmental audits, should ensure effective and safe practice whilst minimizing
      associated risks. Evidence-based radiography will provide the necessary drive for
      future changes in practice as well as further expansion of the radiographer's
      role.

PMID- 11511492
TI  - Percutaneous treatment of pseudoaneurysms using fibrin adhesive.
AB  - This study was performed to assess the safety and efficacy of treatment of
      iatrogenic pseudoaneurysms with fibrin adhesive. 28 patients with iatrogenic
      pseudoaneurysms were treated. The first 20 patients had either at least one
      previously unsuccessful treatment of ultrasound guided compression repair (UGCR),
      a contraindication to UGCR or could not tolerate the procedure. Diagnosis was
      confirmed on ultrasound and angiography and a balloon inflated across the neck of
      the pseudoaneurysm. Fibrin adhesive was injected under ultrasound control
      directly into the pseudoaneurysm sac. The balloon was deflated after 15 min and
      check ultrasound and angiography performed, with a further ultrasound at 24 h.
      The subsequent eight patients underwent embolisation as the first line treatment
      without use of a protective balloon. 16 of the first 20 patients (80%) and all of
      the subsequent 8 patients had successful embolisation of the pseudoaneurysm after
      a single treatment. Two pseudoaneurysms failed to thrombose despite two
      treatments in one case and three treatments in the other, and both required
      surgery. The only significant complication was the development of local
      cellulitis in one patient. In conclusion, embolisation of iatrogenic aneurysms
      with fibrin adhesive is a safe and effective treatment. It should be considered
      as an alternative to surgery and UGCR.

PMID- 11511493
TI  - Renal cortical retention on delayed CT and nephropathy following transcatheter
      arterial chemoembolisation.
AB  - The aim of this study was to examine the relationship between renal cortical
      retention on delayed CT and contrast medium-associated and/or transarterial
      chemoembolisation (TACE)-associated nephropathy following TACE. The authors
      reviewed the findings on 180 treatments in 121 patients with normal serum
      creatinine levels who underwent TACE for liver tumours. Nephropathy was defined
      as an increase in the creatinine level of greater than 0.5 mg x dl(-1) (44
      micromol x l(-1)) and greater than 25% on days 1, 3, 7 or 14 post TACE. Renal
      cortical retention was recognized when CT values for the renal cortex showed
      either mild renal cortical retention (CT value >50) or severe renal cortical
      retention (CT value >100). There was evidence of renal cortical retention in 81
      (45%) cases and of nephropathy in 11 (6%) cases. Only 2% of patients without
      renal cortical retention showed nephropathy, whereas 11% of those with renal
      cortical retention showed nephropathy (p=0.02). Stepwise selection using a
      multivariate logistic regression model showed renal cortical retention and gender
      to be significant factors for nephropathy following TACE. In conclusion, renal
      cortical retention is a useful predicator for nephropathy following TACE. Delayed
      CT could be used not only for assessment of lipiodol retention but also for
      predicting nephropathy.

PMID- 11511494
TI  - Breath-hold MRI in evaluating patients with pectus excavatum.
AB  - Pectus excavatum (PE) is a congenital condition in which the sternum is displaced
      posteriorly with associated changes in the adjacent costal cartilages. The
      aetiology of PE is uncertain although various underlying abnormalities of the
      diaphragm have been implicated. There is sparse information regarding the use of
      fast MRI in evaluating the deformity. Our aims were to use fast MRI to evaluate
      static and respiratory-related dynamic chest wall characteristics, the extent of
      cardiac displacement and diaphragmatic excursion in patients. FLASH and
      TurboFLASH MR sequences in axial and coronal planes were performed on the
      thoraces of six young patients with PE and six individually matched healthy
      controls during full inspiratory and full expiratory breath-holds. The Pectus
      Index was derived from chest wall measurements using axial images. The distances
      of the left and right cardiac borders from the midline were measured using axial
      images, and excursion of the dome of each hemidiaphragm was measured using
      coronal images. The degree of sternal depression worsened substantially in
      expiration. Anterior chest wall movement was similar in the two groups. Patients
      had significantly flatter chests than the controls. There was a trend towards
      leftward cardiac displacement in the patients (maximum distance between left
      heart border and midline during full expiration 99.5 mm in patients and 91.8 mm
      in controls). The right diaphragmatic dome excursion was greater than the left in
      the controls (53.6 mm and 47.4 mm, respectively), but this was not seen in the
      patients (50.2 mm and 50.4 mm, respectively). It is concluded that fast MRI is
      very informative in evaluating skeletal abnormalities, chest wall motion, and
      cardiac and diaphragmatic changes seen in PE.

PMID- 11511495
TI  - Therapeutic effects of simultaneous intraluminal irradiation and intraluminal
      hyperthermia on oesophageal carcinoma.
AB  - An applicator enabling simultaneous intraluminal radiotherapy and intraluminal
      hyperthermia delivery was developed to improve the treatment results for locally
      advanced oesophageal carcinoma. Eight inoperable cases were treated by this
      method. Six cases received 40 Gy external irradiation followed by simultaneous
      intraluminal hyperthermia and radiotherapy (3 Gy and 4 Gy in three cases each)
      once weekly for 3 weeks; the remaining two cases received 50 Gy external
      irradiation followed by simultaneous intraluminal hyperthermia and radiotherapy
      (4 Gy) once weekly for 2 weeks. Hyperthermia was delivered by a radiofrequency
      current thermotherapy instrument for 30 min at an output that raised the
      oesophageal mucosal surface temperature to 42-43 degrees C. Intraluminal
      radiotherapy was delivered with a microSelectron to a submucosal depth of 5 mm
      after the first 15 min of hyperthermia. Four cases achieved complete response,
      with all demonstrating local control. Partial response was obtained in four
      cases, and three of these patients died of local recurrence. There were no
      significant adverse side effects apart from fistula in one case. In conclusion,
      simultaneous intraluminal radiotherapy and hyperthermia may improve the current
      treatment results for locally advanced oesophageal carcinoma.

PMID- 11511496
TI  - Radionuclide radiologist directed nuclear medicine services in district general
      hospitals in the South Thames Region.
AB  - The equipment, staffing levels and imaging workload of all 14 radiologist
      directed nuclear medicine services in district general hospitals in the South
      Thames Region are presented. These are generally single camera departments
      providing a broad range of imaging procedures, including cardiac studies and
      white cell labelling, as well as the more usual renal, lung, thyroid and bone
      examinations. All departments have a high throughput, averaging 2358 examinations
      per year. Departmental staffing levels are variable, with some institutions
      having inadequate consultant radiology sessions free of other commitments as well
      as inadequate physics support. Potentially, these are important quality and legal
      issues that departments may need to address with hospital Trusts and
      Commissioning Agencies. Four small departments provided a service without any
      formally contracted radiologist sessions for nuclear medicine in the
      radiologists' job plans. The three medium sized departments have a closer match
      between sessions contracted and those actually worked, but in only one of these
      did the contracted sessional commitment equal the recommendation of the Nuclear
      Medicine Committee of the Royal College of Physicians. There is a disparity
      between the number of contracted consultant sessions and those actually worked in
      most institutions (86%), being at least two sessions in eight hospitals.
      Recommendations are made regarding the adequacy of some of the elements of
      provision in South Thames and the legal and safety implications for hospital
      Trust management and Commissioning Agencies.

PMID- 11511497
TI  - Patient and staff dose during CT guided biopsy, drainage and coagulation.
AB  - Patient and staff dose during CT guided coagulation of osteoid osteoma, tissue
      biopsy and abscess drainage were evaluated retrospectively on a conventional CT
      scanner and prospectively on a scanner equipped with fluoroscopic CT. The
      computed tomography dose index (CTDI) and the individual dose equivalent, i.e.
      the penetrating dose for workers at a depth of 10 mm tissue, were measured.
      Evaluation of CTDI enabled effective dose and maximum skin entrance doses for the
      patient to be determined. Doses were assessed for 96 CT guided interventions,
      including 16 drainages with average effective doses of 13.5 mSv and 9.3 mSv for
      the conventional CT scanner and the scanner with spiral CT fluoroscopy,
      respectively, 49 biopsies (effective doses of 8 mSv and 6.1 mSv, respectively),
      and 31 coagulations of osteoid osteoma (effective doses of 2.1 mSv and 0.8 mSv,
      respectively). Effective doses to patients were in the same range as those
      observed for regular diagnostic CT examinations. Entrance skin doses were well
      below the 2 Gy threshold for deterministic skin effects on the CT scanner
      equipped with fluoroscopic function (0.03-0.33 Gy), whilst skin doses on the
      conventional scanner were considerably higher (0.09-1.61 Gy). This is mainly
      owing to the fact that on the conventional scanner mAs was rarely reduced for
      scans evaluating needle position whereas low mAs per rotation was selected on the
      scanner with the fluoroscopy option. The maximum dose to a worker measured
      outside the lead apron was 28 microSv for one single procedure. The mean dose per
      procedure was below 10 microSv for radiologists and below 1 microSv for
      radiographers. Correcting for attenuation of the lead apron, the doses to workers
      are very low.

PMID- 11511498
TI  - Differences in effective dose estimation from dose-area product and entrance
      surface dose measurements in intravenous urography.
AB  - In this study, measurements of dose-area product (DAP) and entrance surface dose
      (ESD) were carried out in a sample of 25 adult patients who underwent intravenous
      urography (IVU). These measured quantities were used to estimate the effective
      dose E from the IVU examination, a quantity closely correlated to radiation risk.
      Estimating E involves the use of conversion coefficients that have been
      determined for specific X-ray views in a mathematical phantom. These are obtained
      under conditions which are not usually met in clinical practice. As a result, the
      E estimates using the two different measurable quantities can be quite different.
      Analysis of the calculation procedure suggests that the E estimate using the DAP
      measurements, in addition to being more practical, could be more accurate than
      using ESD measurements, as DAP is sensitive to the X-ray field size settings.
      Furthermore, it is shown that in the absence of the appropriate equipment, a
      reliable E estimate can be obtained from the ESD calculated using the exposure
      data for each X-ray view.

PMID- 11511499
TI  - Radiotherapy equipment--purchase or lease?
AB  - Against a background of increasing demand for radiotherapy equipment, this study
      was undertaken to investigate options for equipment procurement, in particular to
      compare purchase with lease. The perceived advantages of lease are that equipment
      can be acquired within budget and cashflow constraints, with relatively low
      amounts of cash leaving the NHS in the first year, avoiding the necessity of
      capitalizing the equipment and providing protection against the risk of
      obsolescence associated with high technology equipment. The perceived
      disadvantages of leasing are that the Trust does not own the equipment, leasing
      can be more expensive in revenue terms, the tender process is extended and there
      may be lease conditions to be met, which may be costly and/or restrictive. There
      are also a number of technical considerations involved in the leasing of
      radiotherapy equipment that influence the financial analysis and practical
      operation of the radiotherapy service. The technical considerations include
      servicing and planned preventative maintenance, upgrades, spare parts, subsequent
      purchase of "add ons", modification of equipment, research and development work,
      commencement of the lease period, return of equipment at the end of the lease
      period and negotiations at the end of the lease period. A study from Raigmore
      Hospital, Inverness is described, which involves the procurement of new, state-of
      the-art radiotherapy equipment. This provides an overview of the procurement
      process, including a summary of the advantages and disadvantages of leasing, with
      the figures from the financial analysis presented and explained. In addition, a
      detailed description is given of the technical considerations to be taken into
      account in the financial analysis and negotiation of any lease contract.

PMID- 11511500
TI  - Re-irradiation and external hyperthermia in locally advanced, radiation
      recurrent, hormone refractory prostate cancer: a preliminary report.
AB  - The purpose of this report is to present the preliminary results of re
      irradiation and external hyperthermia in patients with locally advanced,
      previously irradiated, hormone refractory prostate cancer. Three consecutive
      patients with symptomatic, locally advanced, previously irradiated and hormone
      refractory prostate cancer were treated with further irradiation (30.6-50 Gy) and
      external hyperthermia (5-8 treatments). All patients had complete resolution of
      symptoms lasting for 12-24 months. Significant tumour shrinkage, including
      complete tumour response, was demonstrated by CT and endoscopy. In one case, at 2
      years after re-treatment, there is continued tumour regression and bone
      regeneration in the pelvis. Two patients had local control of tumour, which
      continued until most recent follow-up at 12 months and more than 24 months,
      respectively. Another case developed local recurrence at 17 months. At most
      recent follow-up, no patient has experienced significant treatment-related side
      effects. In these patients with no other therapeutic alternatives, re-irradiation
      and hyperthermia can provide durable tumour response for more than a year,
      resulting in significant improvement in quality of life. Further clinical studies
      are warranted.

PMID- 11511501
TI  - Hepatic vein transit time of an ultrasound contrast agent: simplified procedure
      using pulse inversion imaging.
AB  - The aim of this study was to ascertain whether a new ultrasound technique, namely
      pulse inversion imaging, could assess the arrival of a contrast agent in the
      hepatic veins, and to describe possible advantages of this procedure in
      determining transit time over a previously described method based upon spectral
      Doppler quantification. 15 subjects were scanned using pulse inversion imaging. A
      bolus injection of 2.5 g Levovist (Schering AG, Berlin, Germany) 300 mg x ml(-1)
      was given into an antecubital vein. Median transit times of 16 s (range 14-20 s)
      were found in patients with liver cirrhosis (n=4), 22 s (range 16-27 s) in
      patients with focal liver lesions (n=8) and 31 s (range 30-32 s) in control
      subjects (n=3). The maximum interobserver variation was 2 s and the maximum
      intraobserver variation was 3 s (n=10). Transit time was assessed by both pulse
      inversion imaging and spectral Doppler quantification in six patients. Comparison
      of the two methods showed transit times within 2 s apart in five patients and
      within 5 s apart in one patient. In conclusion, it is possible to assess transit
      time using pulse inversion imaging. This method is simpler than a previously
      described method requiring computer analysis. Moreover, several liver veins can
      be assessed simultaneously. Different transit times were observed in different
      liver veins in two patients with liver tumours. A short transit time (<27 s)
      appears to be found only in patients with liver disease. After transit time
      assessment, it is possible to use the injected contrast agent for late phase
      imaging of the liver parenchyma.

PMID- 11511502
TI  - Alternative radiographic projections of the ulnar coronoid process.
AB  - We describe two radiological projections that ensure correct imaging of the ulnar
      coronoid process and that can be carried out with minimum mobilization of the
      joint, thus being practical in virtually all patients.

PMID- 11511503
TI  - Retrograde venous invasion causing vertebral metastases in renal cell carcinoma.
AB  - A case of renal cell carcinoma is presented with renal vein and inferior vena
      cava tumour/thrombus extension and vertebral metastases centred on the
      basivertebral veins at three contiguous levels in the low thoracic spine. MRI
      demonstrated tumour in the intervertebral veins, suggesting that the vertebral
      deposits were due to retrograde venous spread. To our knowledge, vertebral
      metastatic deposits due to retrograde venous spread in renal cell carcinoma have
      not been previously demonstrated directly on imaging. A review is given of the
      venous anatomy relevant to this mode of spread.

PMID- 11511504
TI  - Torsion of a normal ovary in a post-pubertal female: unenhanced helical CT
      appearance.
AB  - This case report presents the CT features of torsion of normal adnexa in an adult
      woman. Unenhanced helical CT, initially performed for clinically suspected acute
      ureterolithiasis, established the diagnosis.

PMID- 11511505
TI  - DiGeorge syndrome associated with left lung aplasia.
AB  - We report a patient with clinical and cytogenetic findings consistent with
      DiGeorge-velocardiofacial syndrome and aplasia of the left lung. To the best of
      our knowledge, this is the first reported case of DiGeorge-velocardiofacial
      syndrome associated with unilateral lung aplasia. Gadolinium enhanced three
      dimensional magnetic resonance angiography demonstrated associated right-sided
      aortic arch and left pulmonary artery agenesis.

PMID- 11511506
TI  - CT findings in congenital anomalies of the spleen.
AB  - There is a wide range of congenital anomalies of the spleen. Some are common,
      such as splenic lobulation and accessory spleen. Other less common conditions,
      such as wandering spleen and polysplenia, have particular clinical significance.
      Radiologists need to be aware of the various congenital variants of the spleen in
      order to recognize clinically important anomalies and to avoid mistaking less
      significant ones for an abnormality. In this pictorial review, the embryology of
      congenital anomalies of the spleen as well as their appearance on CT are
      described, diagnostic pitfalls are identified and complications of the anomalies
      are discussed.

PMID- 11511507
TI  - Painful swelling of the thigh.

PMID- 11511508
TI  - Multicentre investigations into uncertainty in neck of femur and total hip DXA
      measurements.

PMID- 11511509
TI  - Only UCP1 can mediate adaptive nonshivering thermogenesis in the cold.
AB  - Adaptive nonshivering thermogenesis may have profound effects on energy balance
      and is therefore therefore is a potential mechanism for counteracting the
      development of obesity. The molecular basis for adaptive nonshivering
      thermogenesis has remained a challenge that sparked acute interest with the
      identification of proteins (UCP2, UCP3, etc.) with high-sequence similarity to
      the original uncoupling protein-1 (UCP1), which is localized only in brown
      adipose tissue. Using UCP1-ablated mice, we examined whether any adaptive
      nonshivering thermogenesis could be recruited by acclimation to cold. Remarkably,
      by successive acclimation, the UCP1-ablated mice could be made to subsist for
      several weeks at 4C during which they had to constantly produce heat at four
      times their resting levels. Despite these extreme requirements for adaptive
      nonshivering thermogenesis, however, no substitution of shivering by any adaptive
      nonshivering thermogenic process occurred. Thus, although the existence of, for
      example, muscular mechanisms for adaptive nonshivering thermogenesis has
      recurrently been implied, we did not find any indication of such thermogenesis.
      Not even during prolonged and enhanced demand for extra heat production was any
      endogenous hormone or neurotransmitter able to recruit any UCP1-independent
      adaptive nonshivering thermogenic process in muscle or in any other organ, and no
      proteins other than UCP1-not even UCP2 or UCP3-therefore have the ability to
      mediate adaptive nonshivering thermogenesis in the cold.

PMID- 11511510
TI  - Recruitment of cdc2 kinase by DNA topoisomerase II is coupled to chromatin
      remodeling.
AB  - Although initiation of chromosome condensation during early prophase is linked
      temporally to the appearance of the mitotic cdc2 kinase in the nucleus, it is not
      known what targets the kinase to the nucleus and how this is coupled to chromatin
      remodeling. We now report that cdc2 kinase forms stable molecular complexes with
      the nuclear enzyme DNA topoisomerase II, which is associated with marked
      stimulation of both DNA binding and catalytic activity of topoisomerase II,
      albeit in a phosphorylation-independent manner. The molecular interaction is
      required for recruitment of cdc2 kinase, as shown by incubation of purified
      enzymes with chicken erythrocyte nuclei, which have neither endogenous
      topoisomerase II nor cdc2 kinase. The physical association between the two
      enzymes alters the DNA/topoisomerase II interaction as shown by pulse-field
      electrophoresis after incubation of intact nuclei with the specific topoisomerase
      II inhibitor VM-26. Furthermore, the presence of both enzymes, but not either
      enzyme alone, is accompanied by extensive chromatin remodeling converting the
      interphase nuclei into precondensation chromosomes with striking resemblance to
      early prophase structures. Our results reveal a novel property of cyclin
      dependent kinases and demonstrate that the recruitment of cdc2 kinase by
      topoisomerase II is coupled to chromatin remodeling.

PMID- 11511511
TI  - Genetic engineering of a hypoallergenic trimer of the major birch pollen allergen
      Bet v 1.
AB  - An estimated 100 million individuals suffer from birch pollen allergy. Specific
      immunotherapy, the only curative allergy treatment, can cause life-threatening
      anaphylactic side effects. Here, we report the genetic engineering of a
      recombinant trimer consisting of three covalently linked copies of the major
      birch pollen allergen, Bet v 1. The trimer exhibited profoundly reduced
      allergenic activity but contained similar secondary structures such as Bet v 1
      wild type, Bet v 1-specific B cell and T-cell epitopes, and induced Th1 cytokine
      release. As immunogen, rBet v 1 trimer induced IgG antibodies, which blocked
      patients' IgE binding to Bet v 1 and related allergens. Thus, rBet v 1 trimer
      represents a novel hypoallergenic vaccine prototype for treatment of one of the
      most frequent allergy forms.

PMID- 11511512
TI  - Altered skin development and impaired proliferative and inflammatory responses in
      transgenic mice overexpressing the glucocorticoid receptor.
AB  - Glucocorticoids (GCs) are potent inhibitors of epidermal proliferation and
      effective anti-inflammatory compounds, which make them the drug of choice for a
      wide range of inflammatory and hyperproliferative skin disorders. GC action is
      mediated via the glucocorticoid receptor (GR). To study the role of GR in skin
      development and the molecular mechanisms underlying its action, we generated
      transgenic mice overexpressing GR in epidermis and other stratified epithelia,
      under the control of the keratin K5 promoter. Newborn mice show altered skin
      development, manifested as variable-sized skin lesions that range from epidermal
      hypoplasia and underdeveloped dysplastic hair follicles to a complete absence of
      this tissue. In the most affected individuals, skin was absent at the cranial and
      umbilical regions, and the vibrissae and eyebrows appear scarce, short, and
      curly. In addition, as a consequence of transgene expression in other
      ectodermally derived epithelia, K5-GR mice exhibited further abnormalities that
      strikingly resemble the clinical findings in patients with ectodermal dysplasia,
      which includes aplasia cutis congenita. In adult transgenic skin, topical
      application of the tumor promoter TPA did not elicit hyperplasia or
      transcriptional induction of several proinflammatory cytokines. This anti
      inflammatory role of GR was due at least in part to interference with NF-kB,
      leading to a strong reduction in the kB-binding activity without altering the
      transcriptional levels of the inhibitor IkBa.

PMID- 11511513
TI  - Proteases produced by activated neutrophils are able to release soluble CD23
      fragments endowed with proinflammatory effects.
AB  - Polymorphonuclear neutrophils (PMNs) are the major source of proteolytic
      activities involved mainly in tissue injuries observed in chronic inflammatory
      disorders. High levels of soluble forms of CD23 (the low-affinity receptor for
      IgE) were found in biological fluids from these patients, and recent reports
      focused on a CD23-mediated regulation of inflammatory response. In this context,
      we show here that co-culture of activated PMN with CD23+ B cells resulted in a
      drastic release of soluble CD23 fragments from the cell surface. This cleavage
      was inhibited by serine proteases inhibitors, including a1-antitrypsin. We next
      demonstrated that purified human leukocyte elastase or cathepsin G efficiently
      cleaved membrane CD23 on B cells with a high specificity. Soluble fragments
      released by serine proteases-mediated CD23 proteolysis stimulated resting
      monocytes to produce oxidative burst and proinflammatory cytokine without any co
      stimulatory signal. This work strongly supports the idea that the capacity of PMN
      derived proteases to release soluble forms of CD23 participates in the
      inflammatory process mediated by these cells.

PMID- 11511514
TI  - Resistance to thromboembolism in PI3Kgamma-deficient mice.
AB  - Platelet aggregation and subsequent thrombosis are the major cause of ischemic
      diseases such as heart attack and stroke. ADP, acting via G protein-coupled
      receptors (GPCRs), is an important signal in thrombus formation and involves
      activation of phosphoinositide 3-kinases (PI3K). When platelets from mice lacking
      the G protein-activated PI3Kgamma isoform were stimulated with ADP, aggregation
      was impaired. Collagen or thrombin, however, evoked a normal response. ADP
      stimulation of PI3Kgamma-deficient platelets resulted in decreased PKB/Akt
      phosphorylation and alpha(IIb)beta(3) fibrinogen receptor activation. These
      effects did not influence bleeding time but protected PI3Kgamma-null mice from
      death caused by ADP-induced platelet-dependent thromboembolic vascular occlusion.
      This result demonstrates an unsuspected, well-defined role for PI3Kgamma
      downstream of ADP and suggests that pharmacological targeting of PI3Kgamma has a
      potential use as antithrombotic therapy.

PMID- 11511515
TI  - Modified testicular expression of stress-associated "readthrough"
      acetylcholinesterase predicts male infertility.
AB  - Male infertility is often attributed to stress. However, the protein or proteins
      that mediate stress-related infertility are not yet known. Overexpression of the
      "readthrough" variant of acetylcholinesterase (AChE-R) is involved in the
      cellular stress response in a variety of mammalian tissues. Here, we report
      testicular overexpression of AChE-R in heads, but not tails, of postmeiotic
      spermatozoa from mice subjected to a transient psychological stress compared with
      age-matched control mice. Transgenic mice overexpressing AChE-R displayed reduced
      sperm counts, decreased seminal gland weight, and impaired sperm motility
      compared with age-matched nontransgenic controls. AChE-R was prominent in meiotic
      phase spermatocytes and in tails, but not heads, of testicular spermatozoa from
      AChE-R transgenic mice. Head-localized AChE-R was characteristic of human sperm
      from fertile donors. In contrast, sperm head AChE-R staining was conspicuously
      reduced in samples from human couples for whom the cause of infertility could not
      be determined, similar to the pattern found in transgenic mice. These findings
      indicate AChE-R involvement in impaired sperm quality, which suggests that it is
      a molecular marker for stress-related infertility.

PMID- 11511516
TI  - Redox-sensitive intermediates mediate angiotensin II-induced p38 MAP kinase
      activation, AP-1 binding activity, and TGF-beta expression in adult ventricular
      cardiomyocytes.
AB  - Cardiac hypertrophy as an adaptation to increased blood pressure leads to an
      increase in ventricular expression of transforming growth factor Cardiac
      hypertrophy as an adaptation to increased blood pressure leads to an increase in
      ventricular expression of transforming growth factor b (TGF-b), probably via the
      renin-angiotensin system. We studied in vivo to determine whether angiotensin II
      affects TGF-b expression independent from mechanical effects caused by the
      concomitant increase in blood pressure and in vitro intracellular signaling
      involved in angiotensin II-dependent TGF-b1 induction. In vivo, the AT1 receptor
      antagonist losartan, but not reduction of blood pressure by hydralazine,
      inhibited the increase in TGF-b1 expression caused by angiotensin II. In vitro,
      angiotensin II caused an induction of TGF-b1 expression in adult ventricular
      cardiomyocytes and induced AP-1 binding activity. Transfection with "decoys"
      directed against the binding site of AP-1 binding proteins inhibited the
      angiotensin II-dependent TGF-b induction. Angiotensin II induced TGF-b expression
      in a p38-MAP kinase-dependent way. p38-MAP kinase activation was diminished in
      presence of the antioxidants or diphenyleneiodium chloride, or by pretreatment
      with antisense nucleotides directed against phox22 and nox, components of smooth
      muscle type NAD(P)H oxidase. Thus, our study identifies a previously unrecognized
      coupling of cardiac AT receptors to a NAD(P)H oxidase complex similar to that
      expressed in smooth muscle cells and identifies p38-MAP kinase activation as an
      important downstream target.

PMID- 11511517
TI  - Overexpression of UCP3 in cultured human muscle lowers mitochondrial membrane
      potential, raises ATP/ADP ratio, and favors fatty acid vs. glucose oxidation.
AB  - The skeletal muscle mitochondrial uncoupling protein-3 (UCP3) promotes substrate
      oxidation, but direct evidence for its metabolic role is lacking. Here, we show
      that UCP3 overexpression in cultured human muscle cells decreased mitochondrial
      membrane potential (DYm). Despite this, the ATP content was not significantly
      decreased compared with control cells, whereas ADP content was reduced and thus
      the ATP/ADP ratio raised. This finding was contrasts with the effect caused by
      the chemical protonophoric uncoupler, CCCP, which lowered DYm, ATP, and the
      ATP/ADP ratio. UCP3-overexpression enhanced oxidation of oleate, regardless of
      the presence of glucose, whereas etomoxir, which blocks fatty acid entry to
      mitochondria, suppressed the UCP3 effect. Glucose oxidation was stimulated in
      UCP3-overexpressing cells, but this effect was inhibited by oleate. UCP3 caused
      weak increase of both 2-Deoxyglucose uptake and glycolytic rate, which differed
      from the marked stimulation by CCCP. We concluded that UCP3 promoted nutrient
      oxidation by lowering DYm and enhanced fatty acid-dependent inhibition of glucose
      oxidation. Unlike the uncoupler CCCP, however, UCP3 raised the ATP/ADP ratio and
      modestly increased glucose uptake and glycolysis. We propose that this
      differential effect provides a biological significance to UCP3, which is up
      regulated in metabolic stress situations where it could be involved in nutrient
      partitioning.

PMID- 11511518
TI  - Cell cycling determines integrin-mediated adhesion in osteoblastic ROS 17/2.8
      cells exposed to space-related conditions.
AB  - Six days of microgravity (Bion10 mission) induced dramatic shape changes in ROS
      17/2.8 osteoblasts (7). During the Foton 11 and 12 space flights, we studied the
      kinetics (0-4 days) of ROS 17/2.8 morphology and adhesion, the relationships
      between adhesion and cell cycle progression after 4 days in space, and
      osteoblastic growth and activity after 6 days in space. Quantitative analysis of
      high-resolution adhesion [focal adhesion area imaged by total interference
      reflection fluorescent microscopy (TIRFM)] and integrin-dependent adhesion
      (imaged on confocal microscope by vinculin and phosphotyrosine staining) as well
      as cell cycle phase classification [Ki-67 staining, S-G2, mitotic cells and G1
      (postmitotic cells)] were performed using programs validated in parabolic flight
      and clinostat. We observed disorganization of the cytoskeleton associated with
      disassembling of vinculin spots and phosphorylated proteins within focal contacts
      with no major change in TIRFM adhesion after 2 and 4 days of microgravity.
      Postmitotic cells, alone, accounted for the differences observed in the whole
      population. They are characterized by immature peripheral contacts with complete
      loss of central spots and decreased spreading. Osteocalcin, P1CP and alkaline
      phosphatase, and proliferation were similar in flight cells and 1 g centrifuge
      and ground controls after 6 days. In conclusion, microgravity substantially
      affected osteoblastic integrin-mediated cell adhesion. ROS17/2.8 cells responded
      differently, whether or not they were cycling by reorganizing adhesion plaque
      topography or morphology. In ROS 17/2.8, this reorganization did not impair
      osteoblastic phenotype.

PMID- 11511519
TI  - Five-lipoxygenase inhibitors can mediate apoptosis in human breast cancer cell
      lines through complex eicosanoid interactions.
AB  - Many arachidonic acid metabolites function in growth signaling for epithelial
      cells, and we previously reported the expression of the major arachidonic acid
      enzymes in human breast cancer cell lines. To evaluate the role of the 5
      lipoxygenase (5-LO) pathway on breast cancer growth regulation, we exposed cells
      to insulinlike growth factor-1 or transferrin, which increased the levels of the
      5-LO metabolite, 5(S)-hydrooxyeicosa-6E,8C,11Z,14Z-tetraenoic acid (5-HETE), by
      radioimmunoassay and high-performance liquid chromatography. Addition of 5-HETE
      to breast cancer cells resulted in growth stimulation, whereas selective
      biochemical inhibitors of 5-LO reduced the levels of 5-HETE and related
      metabolites. Application of 5-LO or 5-LO activating protein-directed inhibitors,
      but not a cyclooxygenase inhibitor, reduced growth, increased apoptosis, down
      regulated bcl-2, up-regulated bax, and increased G1 arrest. Exposure of breast
      cancer cells to a 5-LO inhibitor up-regulated peroxisome proliferator-activated
      receptor (PPAR)a and PPARg expression, and these same cells were growth inhibited
      when exposed to relevant PPAR agonists. These results suggest that disruption of
      the 5-LO signaling pathway mediates growth arrest and apoptosis in breast cancer
      cells. Additional experiments suggest that this involves the interplay of several
      factors, including the loss of growth stimulation by 5-LO products, the induction
      of PPARg, and the potential activation of PPARg by interactions with shunted
      endoperoxides.

PMID- 11511521
TI  - Differentiation and migration of astrocyte precursor cells and astrocytes in
      human fetal retina: relevance to optic nerve coloboma.
AB  - The presence of astrocyte precursor cells (APCs) and time course and topography
      of astrocyte differentiation during development were investigated by triple-label
      immunohistochemistry with intact fetal and adult human retinas. Throughout
      retinal development and adulthood, expression of Pax2 was restricted to cells of
      the astrocytic lineage. Three distinct stages of astrocytic differentiation were
      identified during development: i) Pax2+/vimentin+/GFAP- APCs; ii)
      Pax2+/vimentin+/GFAP+ immature perinatal astrocytes; and iii) Pax2+/vimentin
      /GFAP+ mature perinatal astrocytes. In adult, cells with the antigenic phenotype
      of mature perinatal astrocytes were restricted to a region surrounding the optic
      nerve head (ONH), whereas cells at a fourth stage of differentiation, adult
      astrocytes (Pax2-/vimentin-/GFAP+), were apparent throughout the vascularized
      retina. APC appearance was centered around the ONH and preceded the appearance of
      perinatal astrocytes. A cluster of Pax2+ somas was also present in a small region
      surrounding the ONH at the ventricular surface of the developing retina, which
      suggests the existence of two distinct sites of astrocytic differentiation. The
      coincidence in the location of APCs and perinatal astrocytes at the ventricular
      zone with that of optic nerve colobomas, together with the association of Pax2
      gene mutations with this condition, suggests that coloboma formation may result
      from impaired astrocyte differentiation during development.

PMID- 11511520
TI  - Neuronal nitric oxide synthase: a substrate for SHP-1 involved in sst2
      somatostatin receptor growth inhibitory signaling.
AB  - Somatostatin receptor sst2 is an inhibitory G protein-coupled receptor, which
      inhibits normal and tumor cell growth by a mechanism involving the tyrosine
      phosphatase SHP-1. We reported previously that SHP-1 associates transiently with
      and is activated by sst2 and is a critical component for sst2 growth inhibitory
      signaling. Here, we demonstrate that in Chinese hamster ovary cells expressing
      sst2, SHP-1 is associated at the basal level with the neuronal nitric oxide
      synthase (nNOS). Following sst2 activation by the somatostatin analog RC-160, SHP
      1 rapidly recruits nNOS tyrosine dephosphorylates and activates it. The resulting
      NO activates guanylate cyclase and inhibits cell proliferation. Coexpression of a
      catalytically inactive SHP-1 mutant with sst2 blocks RC-160-induced nNOS
      dephosphorylation and activation, as well as guanylate cyclase activation. In
      mouse pancreatic acini, RC-160 treatment reduces nNOS tyrosine phosphorylation
      accompanied by an increase of its activity. By opposition, in acini from viable
      motheaten (mev/mev) mice, which express a markedly inactive SHP-1, RC-160 has no
      effect on nNOS activity. Finally, expression of a dominant-negative form of nNOS
      prevents both RC-160-induced p27 up-regulation and cell proliferation inhibition.
      We therefore identified nNOS as a novel SHP-1 substrate critical for sst2-induced
      cell-growth arrest.

PMID- 11511522
TI  - Membrane-type matrix metalloproteinase-1 and -3 activity in primate smooth muscle
      cells.
AB  - Membrane-type matrix metalloproteinases-1 and -3 (MT1- and MT3-MMPs) are
      expressed by activated smooth muscle cells (SMCs) both in vitro and in vivo (19).
      To define their functions in SMCs, we transduced MT1- and MT3-MMP cDNAs into
      baboon SMCs by using adenoviral vectors. Overexpression of MT1-MMP increased the
      conversion of proMMP-2 to the intermediate and active forms. In contrast, in MT3
      MMP-overexpressing cells, MMP-2 was activated partially. Immunoblot analyses
      revealed that MT1-MMP protein was present in the SMCs and accumulated in the
      presence of the synthetic MMP inhibitor, BB94, or tissue inhibitor of
      metalloproteinase-2 (TIMP-2). However, MT3-MMP protein was detectable only when
      BB94, but not TIMP-2, was present. Zymographic analyses showed that MT3-MMP had
      much stronger casein- and gelatin-degrading activities than did MT1-MMP.
      Furthermore, when MT3-MMP and MT1-MMP were coexpressed, MT1-MMP degradation was
      enhanced; this result supports the possibility that MT3-MMP can degrade MT1-MMP.
      SMCs overexpressing either MT1- or MT3-MMP exhibited altered morphology, without
      changing their proliferation. This alteration was prevented by BB94 addition. The
      cells, which underwent this change, showed reduced adhesion to both collagen and
      fibronectin and increased migration in a Boyden chamber. The present study
      demonstrates that MT1- and MT3-MMPs have different enzymatic activities but may
      nevertheless affect SMC function in the same way.

PMID- 11511523
TI  - Genome resource utilization during prokaryotic development.
AB  - The distributions of synthesis rates of expressed proteins in a liquid batch
      culture of the prokaryote S. coelicolor during 3 days' growth have been analyzed
      by using a law governing the relation between the synthesis rates and the
      corresponding ranks in a list of rates (the so-called simplified canonical law,
      scl), which we have found previously to characterize the distribution of
      prokaryotic protein expression. The scl remains valid throughout development and
      the two parameters of the distribution, q and r, evolve in a highly
      characteristic and revealing way. q is a measure of the degree to which available
      genomic resources are used, in the sense of exploiting their potential diversity.
      The passage from one developmental phase to another is marked by a sharp peak in
      q, as these resources are fully mobilized to deal with a crisis (i.e., exhaustion
      of the habitual food supply). This is followed by an even more pronounced trough,
      as the organism briefly focuses its resources on synthesizing just those proteins
      most essential for survival, especially those hitherto unavailable and needed for
      metabolizing the new nutrient source. The parameter r indicates redundancy among
      the most abundantly expressed proteins: higher r corresponds to more diversity;
      i.e., less duplication of function, hence less robustness. This parameter is
      relatively steady throughout the development of the culture, except for a
      pronounced peak during the developmental phase transition. This corresponds to
      the "emergency mode" characterized by extremely low q, during which a minimum
      repertoire of proteins is expressed.

PMID- 11511524
TI  - Early growth-responsive-1-dependent manganese superoxide dismutase gene
      transcription mediated by platelet-derived growth factor.
AB  - Manganese superoxide dismutase Mn-SOD plays a major role in protecting
      mitochondria from oxidative damage. Overexpression of Mn-SOD maintains cell
      survival under conditions that lead to apoptotic death. In addition to the
      antioxidative enzyme, platelet-derived growth factor (PDGF) is a principal
      survival factor that inhibits apoptosis and promotes proliferation by activating
      survival signaling pathways in various cells. Here we show that PDGF induced the
      expression of the Mn-SOD gene in NIH3T3 cells, and its induction was associated
      with early growth response-1 (Egr-1), a transcription factor. An electrophoretic
      mobility shift assay demonstrated that Egr-1 bound to the proximal promoter of
      the Mn-SOD gene in response to PDGF. The proximal promoter region of Mn-SOD was
      shown to be transcriptionally responsive to both basal and PDGF stimulation by
      transfection studies. Forced expression of Egr-1 in the cells activated Mn-SOD
      transcription in a dose-dependent manner. The pathway by which PDGF induced Egr-1
      involved the mitogen-activated protein kinase kinase-1 (MEK1) and extracellular
      signal-regulated kinases 1 and 2 (ERK1/2), because the effect of PDGF on the
      induction of Egr-1 was blocked by U0126, a specific MEK1 inhibitor. These
      findings indicate that the induction of Mn-SOD is part of the anti-apoptotic
      properties mediated by PDGF.

PMID- 11511525
TI  - Nonanaphylactic synthetic peptides derived from B cell epitopes of the major
      grass pollen allergen, Phl p 1, for allergy vaccination.
AB  - Worldwide more than 200 million individuals are allergic to group 1 grass pollen
      allergens. We have used the major timothy grass pollen allergen Phl p 1, which
      cross-reacts with most grass-, corn-, and monocot-derived group 1 allergens to
      develop a generally applicable strategy for the production of hypoallergenic
      allergy vaccines. On the basis of the experimentally determined B cell epitopes
      of Phl p 1, we have synthesized five synthetic peptides. These peptides are
      derived from the major Phl p 1 IgE epitopes and were between 28-32 amino acids
      long. We demonstrate by nuclear magnetic resonance that the peptides exhibit no
      secondary and tertiary structure and accordingly failed to bind IgE antibodies
      from grass pollen allergic patients. The five peptides, as well as an equimolar
      mixture thereof, lacked allergenic activity as demonstrated by basophil histamine
      release and skin test experiments in grass pollen allergic patients. When used as
      immunogens in mice and rabbits, the peptides induced protective IgG antibodies,
      which recognized the complete Phl p 1 wild-type allergen and group 1 allergens
      from other grass species. Moreover, peptide-induced antibodies inhibited the
      binding of grass pollen allergic patients IgE antibodies to the wild-type
      allergen. We thus demonstrate that synthetic hypoallergenic peptides derived from
      B cell epitopes of major allergens represent safe vaccine candidates for the
      treatment of IgE- mediated allergies.

PMID- 11511526
TI  - Mechanisms of inhibition of the Ras-MAP kinase signaling pathway in 30.7b Ras 12
      cells by tea polyphenols (-)-epigallocatechin-3-gallate and theaflavin-3,3'
      digallate.
AB  - Our previous study showed that tea polyphenols inhibited MAP kinase and AP-1
      activities in mouse epidermal JB6 cells and the corresponding H-ras-transformed
      cell line 30.7b Ras 12. The present study investigated the mechanisms of this
      inhibition. The cells were incubated with (-)-epigallocatechin-3-gallate (EGCG)
      or theaflavin-3,3'-digallate (TFdiG) (20 mM) for different times, and the cell
      lysate was analyzed by immunoblotting. EGCG treatment decreased the levels of
      phospho-Erk1/2 and -MEK1/2 time-dependently (by 60% at 60 min). TFdiG lowered
      their levels by 38%-50% at 15 min. TFdiG effectively decreased total Raf-1
      protein levels, most likely through lysosomal degradation. EGCG did not affect
      protein levels or the activity of Raf-1 significantly but decreased its
      association with MEK1 as determined by co-immunoprecipitation. In addition, EGCG
      and TFdiG (10 mM) inhibited the phosphorylation of Elk-1 by isolated phospho
      Erk1/2 in vitro. This inhibition of Erk1/2 activity is Elk-1 concentration
      dependent and ATP concentration-independent, which suggests that EGCG and TFdiG
      interfere with the binding of the protein substrate to the kinase. The presently
      demonstrated specific mechanisms of inhibition of MAP kinases by EGCG and TFdiG
      may help us to understand the effects of tea consumption on cancer, inflammatory
      diseases, and cardiovascular diseases.

PMID- 11511527
TI  - Contribution of cyclooxygenase 2 to liver regeneration after partial hepatectomy.
AB  - Partial hepatectomy (PH) triggers a rapid regenerative response in the remaining
      tissue to reinstate the organ function and the cell numbers. Among the molecules
      that change in the course of regeneration is an accumulation of prostaglandin E2
      in the sera of rats with PH. Analysis of the cyclooxygenase (COX) isoenzymes in
      the remnant liver showed the preferential expression of COX-2 in hepatocytes.
      Cultured regenerating hepatocytes expressed significant levels of COX-2, a
      process that was not observed in the sham counterparts. Maximal expression of COX
      2 was detected 16 h after PH with increased levels present even at 96 h.
      Pharmacological inhibition of COX-2 activity with NS398 shunted the up-regulation
      of cell proliferation after PH, which suggests a positive interaction of
      prostaglandins with the progression of the cell cycle. Similar results were
      obtained after PH of mice lacking the COX-2 gene. The expression of COX-2 in
      regenerating liver was concomitant with a decrease in CCAAT-enhancer binding
      protein (C/EBP-a) level and an increase in the expression of C/EBP-b and C/EBP-d.
      These results suggest a contribution of the enhanced synthesis of prostaglandins
      to liver regeneration observed after PH.

PMID- 11511528
TI  - The mitochondrial permeability transition initiates autophagy in rat hepatocytes.
AB  - Cells degrade excess and effete organelles by the process of autophagy.
      Autophagic stimulation of rat hepatocytes by serum deprivation and glucagon (1 M)
      caused a fivefold increase of spontaneously depolarizing mitochondria to about
      1.5% of total mitochondria after 90 min. Cyclosporin A (CsA, 5 M), an
      immunosuppressant that blocks the mitochondrial permeability transition (MPT),
      prevented this depolarization. Depolarized mitochondria moved into acidic
      vacuoles labeled by LysoTracker Red. These autophagosomes also increased several
      fold after autophagic stimulation. CsA blocked autophagosomal proliferation,
      whereas tacrolimus, an immunosuppressant that does not block the MPT, did not. In
      conclusion, the MPT initiates mitochondrial depolarization after autophagic
      stimulation and the subsequent sequestration of mitochondria into autophagosomes.

PMID- 11511529
TI  - In situ expression of corticotropin-releasing hormone (CRH) and
      proopiomelanocortin (POMC) genes in human skin.
AB  - Systemic stresses induce corticotropin-releasing hormone (CRH) expression in
      hypothalamus. CRH is released to the pituitary gland, where it stimulates
      proopiomelanocortin (POMC) production acting via the CRH receptor (CRH-R). CRH
      and POMC peptides are also detected in sites outside of the central nervous
      system (CNS), such as the skin. However, it has not been elucidated whether these
      peptides detected in the skin are derived from CNS or are produced locally. Using
      immunohistochemical and in situ reverse-transcription (RT)-PCR techniques, we
      demonstrated coexpression of CRH and POMC mRNAs in the epidermis and
      pilosebaceous units of the human skin. This coexpression was confirmed by the
      combination of laser-capture microdissection (LCM) with RT-PCR, analyzing mRNA
      expressions in captured sebaceous cells. Immunoreactivities and expressions of
      CRH and POMC mRNAs were strong in inflammatory lesions, melanocytic nevus,
      seborrheic keratosis, and also in the periphery of the benign tumor. These
      findings suggest that CRH and POMC peptides are produced locally in the skin and
      are regulated by inflammatory cells as well as by autocrine mechanisms. The skin
      may have "a local stress response system," whose activity is mediated by CRH and
      POMC peptides, in an equivalent to hypothalamus-pituitary adrenal axis.

PMID- 11511530
TI  - N1-acetyl-N2-formyl-5-methoxykynuramine, a biogenic amine and melatonin
      metabolite, functions as a potent antioxidant.
AB  - The biogenic amine The biogenic amine N1-acetyl-N2-formyl-5-methoxykynuramine
      (AFMK) was investigated for its potential antioxidative capacity. AFMK is a
      metabolite generated through either an enzymatic or a chemical reaction pathway
      from melatonin. The physiological function of AFMK remains unknown. To our
      knowledge, this report is the first to document the potent antioxidant action of
      this biogenic amine. Cyclic voltammetry (CV) shows that AFMK donates two
      electrons at potentials of 456 mV and 668 mV, and therefore it functions as a
      reductive force. This function contrasts with all other physiological
      antioxidants that donate a single electron only when they neutralize free
      radicals. AFMK reduced 8-hydroxydeoxyguanosine formation induced by the
      incubation of DNA with oxidants significantly. Lipid peroxidation resulting from
      free radical damage to rat liver homogenates was also prevented by the addition
      of AFMK. The inhibitory effects of AFMK on both DNA and lipid damage appear to be
      dose-response related. In cell culture, AFMK efficiently reduced hippocampal
      neuronal death induced by either hydrogen peroxide, glutamate, or amyloid b25-35
      peptide. AFMK is a naturally occurring molecule with potent free radical
      scavenging capacity (donating two electrons/molecule) and thus may be a valuable
      new antioxidant for preventing and treating free radical-related disorders.

PMID- 11511531
TI  - Preferential transduction of neurons by canine adenovirus vectors and their
      efficient retrograde transport in vivo.
AB  - In the central nervous system (CNS), there are innate obstacles to the
      modification of neurons: their relative low abundance versus glia and
      oligodendrocytes, the inaccessibility of certain target populations, and the
      volume one can inject safely. Our aim in this study was to characterize the in
      vivo efficacy of a novel viral vector derived from a canine adenovirus (CAV-2).
      Here we show that CAV-2 preferentially transduced i) rat olfactory sensory
      neurons; ii) rodent CNS neurons in vitro and in vivo; and, more clinically
      relevant, iii) neurons in organotypic slices of human cortical brain. CAV-2 also
      showed a high disposition for retrograde axonal transport in vivo. We examined
      the molecular basis of neuronal targeting by CAV-2 and suggest that due to CAR
      (coxsackie adenovirus receptor) expression on neuronal cells-and not
      oligodendrocytes, glia, myofibers, and nasal epithelial cells-CAV-2 vectors
      transduced neurons preferentially in these diverse tissues.

PMID- 11511532
TI  - Increased expression of UBF is a critical determinant for rRNA synthesis and
      hypertrophic growth of cardiac myocytes.
AB  - Recent evidence suggests that increased translational efficiency of existing
      ribosomes alone is insufficient to account for the hypertrophic growth of
      cardiomyocytes and that synthesis of new functional ribosomes must occur. The
      rate-limiting step in ribosome accumulation is the transcription of the ribosomal
      45S genes (rDNA) by RNA polymerase I. Our previous studies have demonstrated that
      increases in the expression of the rDNA transcription factor UBF correlated with
      hypertrophy of neonatal cardiomyocytes. These studies expand this observation to
      examine directly the hypothesis that increased UBF levels are an essential
      requirement for the initiation of cardiac hypertrophy. We demonstrate that the
      introduction of UBF antisense RNA into myocytes, using adenovirus approaches,
      efficiently inhibits UBF accumulation during induction of cardiomyocyte
      hypertrophy. Moreover, this approach results in a significant reduction in rDNA
      transcription, rRNA levels, and protein accumulation, which are all the hallmarks
      of cardiac growth. Furthermore, UBF antisense RNA expression did not alter re
      expression of the fetal gene program, which confirmed that the effect was
      specific for transcription by RNA polymerase I. These findings demonstrate that
      an increase in rRNA synthesis is required for hypertrophy of cardiomyocytes and
      also implicate UBF as a major regulatory factor in this process. Approaches that
      target UBF activity may be of therapeutic use in the regression of
      pathophysiological cardiac hypertrophy.

PMID- 11511533
TI  - Deconstructing myc.

PMID- 11511534
TI  - The extrusion-capture model for chromosome partitioning in bacteria.

PMID- 11511535
TI  - Regulation of cyclin D2 gene expression by the Myc/Max/Mad network: Myc-dependent
      TRRAP recruitment and histone acetylation at the cyclin D2 promoter.
AB  - Myc oncoproteins promote cell cycle progression in part through the
      transcriptional up-regulation of the cyclin D2 gene. We now show that Myc is
      bound to the cyclin D2 promoter in vivo. Binding of Myc induces cyclin D2
      expression and histone acetylation at a single nucleosome in a MycBoxII/TRRAP
      dependent manner. Down-regulation of cyclin D2 mRNA expression in differentiating
      HL60 cells is preceded by a switch of promoter occupancy from Myc/Max to Mad/Max
      complexes, loss of TRRAP binding, increased HDAC1 binding, and histone
      deacetylation. Thus, recruitment of TRRAP and regulation of histone acetylation
      are critical for transcriptional activation by Myc.

PMID- 11511536
TI  - A novel labeling technique reveals a function for histone H2A/H2B dimer tail
      domains in chromatin assembly in vivo.
AB  - During S phase in eukaryotes, assembly of chromatin on daughter strands is
      thought to be coupled to DNA replication. However, conflicting evidence exists
      concerning the role of the highly conserved core histone tail domains in this
      process. Here we present a novel in vivo labeling technique that was used to
      examine the role of the amino-terminal tails of the H2A/H2B dimer in replication
      coupled assembly in live cells. Our results show that these domains are
      dispensable for nuclear import but at least one tail is required for replication
      dependent, active assembly of H2A/H2B dimers into chromatin in vivo.

PMID- 11511537
TI  - COUP-TFI: an intrinsic factor for early regionalization of the neocortex.
AB  - Regionalization of the cerebral cortex is thought to involve two phases: an early
      regionalization phase and a later refinement phase. It has been shown that early
      regionalization of the neocortex does not require thalamic inputs and is
      regulated by intrinsic factors. Recently, two such intrinsic factors, Pax6 and
      Emx2, have been identified. In this study, we identified COUP-TFI as a regulatory
      factor for early neocortical regionalization. The spatial and temporal expression
      pattern of COUP-TFI suggested a role in specification of the neocortex and in
      maintaining cortical identity. Altered region-specific expression of marker genes
      in the cortex as well as miswired area-specific connections between the cortex
      and the thalamus in COUP-TFI null mice indicate COUP-TFI plays a critical role in
      regulating early regionalization. Our results substantiate that COUP-TFI, an
      intrinsic factor, may work in concert with Pax6 and Emx2 to specify neocortical
      identity.

PMID- 11511538
TI  - A DNA replication-arrest site RTS1 regulates imprinting by determining the
      direction of replication at mat1 in S. pombe.
AB  - Mating-type switching in Schizosaccharomyces pombe involves a strand-specific,
      alkali-labile imprint at the mat1 (mating-type) locus. The imprint is synthesized
      during replication in a swi1, swi3, and polymerase alpha (swi7) dependent manner
      and is dependent on mat1 being replicated in a specific direction. Here we show
      that the direction of replication at mat1 is controlled by a cis-acting polar
      terminator of replication (RTS1). Two-dimensional gel analysis of replication
      intermediates reveals that RTS1 only terminates replication forks moving in the
      centromere-distal direction. A genetic analysis shows that RTS1 optimizes the
      imprinting process. Transposing the RTS1 element to the distal side of mat1
      abolishes imprinting of the native mat1 allele but restores imprinting of an
      otherwise unimprinted inverted mat1 allele. These data provide conclusive
      evidence for the "direction of replication model" that explains the asymmetrical
      switching pattern of S. pombe, and identify a DNA replication-arrest element
      implicated in a developmental process. Such elements could play a more general
      role during development and differentiation in higher eukaryotes by regulating
      the direction of DNA replication at key loci.

PMID- 11511539
TI  - Binding of c-Myc to chromatin mediates mitogen-induced acetylation of histone H4
      and gene activation.
AB  - The Myc protein binds DNA and activates transcription by mechanisms that are
      still unclear. We used chromatin immunoprecipitation (ChIP) to evaluate Myc
      dependent changes in histone acetylation at seven target loci. Upon serum
      stimulation of Rat1 fibroblasts, Myc associated with chromatin, histone H4 became
      locally hyperacetylated, and gene expression was induced. These responses were
      lost or severely impaired in Myc-deficient cells, but were restored by adenoviral
      delivery of Myc simultaneous with mitogenic stimulation. When targeted to
      chromatin in the absence of mitogens, Myc directly induced H4 acetylation. In
      addition, Myc recruited TRRAP to chromatin, consistent with a role for this
      cofactor in histone acetylation. Finally, unlike serum, Myc alone was very
      inefficient in inducing expression of most target genes. Myc therefore governs a
      step, most likely H4 acetylation, that is required but not sufficient for
      transcriptional activation. We propose that Myc acts as a permissive factor,
      allowing additional signals to activate target promoters.

PMID- 11511540
TI  - Suppression of cap-dependent translation in mitosis.
AB  - Cap-dependent translation is mediated by eIF4F, a protein complex composed of
      three subunits as follows: eIF4E, which recognizes the mRNA 5' cap structure;
      eIF4A, an RNA-helicase; and eIF4G, a scaffolding protein that binds eIF4E, eIF4A,
      and the eIF4E-kinase Mnk1 simultaneously. eIF4E is hypophosphorylated and cap
      dependent translation is reduced at mitosis. Here, we show that 4E-BP1, a
      suppressor of eIF4E function, is also hypophosphorylated in mitosis, resulting in
      disruption of the eIF4F complex. Consequently, eIF4E is sequestered from the
      eIF4G/Mnk1 complex. These results explain the specific inhibition of cap
      dependent translation in mitosis and also explain how eIF4E is rendered
      hypophosphorylated during mitosis. Furthermore, eIF4E interaction with eIF4GII is
      strongly decreased coincident with hyperphosphorylation of eIF4GII. Thus,
      inhibition of cap-dependent translation in mitosis results from a combination of
      phosphorylation modifications leading to eIF4F complex disruption.

PMID- 11511541
TI  - Sequential actions of BMP receptors control neural precursor cell production and
      fate.
AB  - Bone morphogenetic proteins (BMPs) have diverse and sometimes paradoxical effects
      during embryonic development. To determine the mechanisms underlying BMP actions,
      we analyzed the expression and function of two BMP receptors, BMPR-IA and BMPR
      IB, in neural precursor cells in vitro and in vivo. Neural precursor cells always
      express Bmpr-1a, but Bmpr-1b is not expressed until embryonic day 9 and is
      restricted to the dorsal neural tube surrounding the source of BMP ligands. BMPR
      IA activation induces (and Sonic hedgehog prevents) expression of Bmpr-1b along
      with dorsal identity genes in precursor cells and promotes their proliferation.
      When BMPR-IB is activated, it limits precursor cell numbers by causing mitotic
      arrest. This results in apoptosis in early gestation embryos and terminal
      differentiation in mid-gestation embryos. Thus, BMP actions are first inducing
      (through BMPR-IA) and then terminating (through BMPR-IB), based on the
      accumulation of BMPR-IB relative to BMPR-IA. We describe a feed-forward mechanism
      to explain how the sequential actions of these receptors control the production
      and fate of dorsal precursor cells from neural stem cells.

PMID- 11511542
TI  - Active repression of RAR signaling is required for head formation.
AB  - The retinoic acid receptors (RARs) recruit coactivator and corepressor proteins
      to activate or repress the transcription of target genes depending on the
      presence of retinoic acid (RA). Despite a detailed molecular understanding of how
      corepressor complexes function, there is no in vivo evidence to support a
      necessary function for RAR-mediated repression. Signaling through RARs is
      required for patterning along the anteroposterior (A-P) axis, particularly in the
      hindbrain and posterior, although the absence of RA is required for correct
      anterior patterning. Because RARs and corepressors are present in regions in
      which RA is absent, we hypothesized that repression mediated through unliganded
      RARs might be important for anterior patterning. To test this hypothesis,
      specific reagents were used that either reduce or augment RAR-mediated
      repression. Derepression of RAR signaling by expressing a dominant-negative
      corepressor resulted in embryos that exhibited phenotypes similar to those
      treated by RA. Anterior structures such as forebrain and cement gland were
      greatly reduced, as was the expression of molecular markers. Enhancement of
      target gene repression using an RAR inverse agonist resulted in up-regulation of
      anterior neural markers and expansion of anterior structures. Morpholino
      antisense oligonucleotide-mediated RARalpha loss-of-function phenocopied the
      effects of RA treatment and dominant-negative corepressor expression.
      Microinjection of wild-type or dominant-negative RARalpha rescued the morpholino
      phenotype, confirming that RAR is functioning anteriorly as a transcriptional
      repressor. Lastly, increasing RAR-mediated repression potentiated head-inducing
      activity of the growth factor inhibitor cerberus, whereas releasing RAR-mediated
      repression blocked cerberus from inducing ectopic heads. We conclude that RAR
      mediated repression of target genes is critical for head formation. This
      requirement establishes an important biological role for active repression of
      target genes by nuclear hormone receptors and illustrates a novel function for
      RARs during vertebrate development.

PMID- 11511543
TI  - A conserved MYB transcription factor involved in phosphate starvation signaling
      both in vascular plants and in unicellular algae.
AB  - Plants have evolved a number of adaptive responses to cope with growth in
      conditions of limited phosphate (Pi) supply involving biochemical, metabolic, and
      developmental changes. We prepared an EMS-mutagenized M(2) population of an
      Arabidopsis thaliana transgenic line harboring a reporter gene specifically
      responsive to Pi starvation (AtIPS1::GUS), and screened for mutants altered in Pi
      starvation regulation. One of the mutants, phr1 (phosphate starvation response
      1), displayed reduced response of AtIPS1::GUS to Pi starvation, and also had a
      broad range of Pi starvation responses impaired, including the responsiveness of
      various other Pi starvation-induced genes and metabolic responses, such as the
      increase in anthocyanin accumulation. PHR1 was positionally cloned and shown be
      related to the PHOSPHORUS STARVATION RESPONSE 1 (PSR1) gene from Chlamydomonas
      reinhardtii. A GFP::PHR1 protein fusion was localized in the nucleus
      independently of Pi status, as is the case for PSR1. PHR1 is expressed in Pi
      sufficient conditions and, in contrast to PSR1, is only weakly responsive to Pi
      starvation. PHR1, PSR1, and other members of the protein family share a MYB
      domain and a predicted coiled-coil (CC) domain, defining a subtype within the MYB
      superfamily, the MYB-CC family. Therefore, PHR1 was found to bind as a dimer to
      an imperfect palindromic sequence. PHR1-binding sequences are present in the
      promoter of Pi starvation-responsive structural genes, indicating that this
      protein acts downstream in the Pi starvation signaling pathway.

PMID- 11511544
TI  - The loop domain of heat shock transcription factor 1 dictates DNA-binding
      specificity and responses to heat stress.
AB  - Eukaryotic heat shock transcription factors (HSF) regulate an evolutionarily
      conserved stress-response pathway essential for survival against a variety of
      environmental and developmental stresses. Although the highly similar HSF family
      members have distinct roles in responding to stress and activating target gene
      expression, the mechanisms that govern these roles are unknown. Here we identify
      a loop within the HSF1 DNA-binding domain that dictates HSF isoform specific DNA
      binding in vitro and preferential target gene activation by HSF family members in
      both a yeast transcription assay and in mammalian cells. These characteristics of
      the HSF1 loop region are transposable to HSF2 and sufficient to confer DNA
      binding specificity, heat shock inducible HSP gene expression and protection from
      heat-induced apoptosis in vivo. In addition, the loop suppresses formation of the
      HSF1 trimer under basal conditions and is required for heat-inducible
      trimerization in a purified system in vitro, suggesting that this domain is a
      critical part of the HSF1 heat-stress-sensing mechanism. We propose that this
      domain defines a signature for HSF1 that constitutes an important determinant for
      how cells utilize a family of transcription factors to respond to distinct
      stresses.

PMID- 11511545
TI  - Functional antagonism between E2F family members.
AB  - E2F is a heterogenous transcription factor and its role in cell cycle control
      results from the integrated activities of many different E2F family members.
      Unlike mammalian cells, that have a large number of E2F-related genes, the
      Drosophila genome encodes just two E2F genes, de2f1 and de2f2. Here we show that
      de2f1 and de2f2 provide different elements of E2F regulation and that they have
      opposing functions during Drosophila development. dE2F1 and dE2F2 both
      heterodimerize with dDP and bind to the promoters of E2F-regulated genes in vivo.
      dE2F1 is a potent activator of transcription, and the loss of de2f1 results in
      the reduced expression of E2F-regulated genes. In contrast, dE2F2 represses the
      transcription of E2F reporters and the loss of de2f2 function results in
      increased and expanded patterns of gene expression. The loss of de2f1 function
      has previously been reported to compromise cell proliferation. de2f1 mutant
      embryos have reduced expression of E2F-regulated genes, low levels of DNA
      synthesis, and hatch to give slow-growing larvae. We find that these defects are
      due in large part to the unchecked activity of dE2F2, since they can be
      suppressed by mutation of de2f2. Examination of eye discs from de2f1; de2f2
      double-mutant animals reveals that relatively normal patterns of DNA synthesis
      can occur in the absence of both E2F proteins. This study shows how repressor and
      activator E2Fs are used to pattern transcription and how the net effect of E2F on
      cell proliferation results from the interplay between two types of E2F complexes
      that have antagonistic functions.

PMID- 11511546
TI  - Functional comparison of the nematode Hox gene lin-39 in C. elegans and P.
      pacificus reveals evolutionary conservation of protein function despite
      divergence of primary sequences.
AB  - Hox transcription factors have been implicated in playing a central role in the
      evolution of animal morphology. Many studies indicate the evolutionary importance
      of regulatory changes in Hox genes, but little is known about the role of
      functional changes in Hox proteins. In the nematodes Pristionchus pacificus and
      Caenorhabditis elegans, developmental processes can be compared at the cellular,
      genetic, and molecular levels and differences in gene function can be identified.
      The Hox gene lin-39 is involved in the regulation of nematode vulva development.
      Comparison of known lin-39 mutations in P. pacificus and C. elegans revealed both
      conservation and changes of gene function. Here, we study evolutionary changes of
      lin-39 function using hybrid transgenes and site-directed mutagenesis in an in
      vivo assay using C. elegans lin-39 mutants. Our data show that despite the
      functional differences of LIN-39 between the two species, Ppa-LIN-39, when driven
      by Cel-lin-39 regulatory elements, can functionally replace Cel-lin-39.
      Furthermore, we show that the MAPK docking and phosphorylation motifs unique for
      Cel-LIN-39 are dispensable for Cel-lin-39 function. Therefore, the evolution of
      lin-39 function is driven by changes in regulatory elements rather than changes
      in the protein itself.

PMID- 11511547
TI  - What comes after macrolides and other motilin stimulants?

PMID- 11511548
TI  - H pylori: the bug is not all bad.

PMID- 11511549
TI  - Beyond acid suppressants in gastro-oesophageal reflux disease.

PMID- 11511550
TI  - Ulcerative colitis extent varies with time but endoscopic appearances may be
      deceptive.

PMID- 11511551
TI  - Gastric leptin and Helicobacter pylori infection.
AB  - BACKGROUND: Leptin regulates feeding behaviour and therefore may be a mediator of
      anorexia associated with acute and chronic inflammation. Recently, leptin mRNA
      and leptin protein were found in the gastric epithelium. AIM: The aim of the
      present study was to examine the effect of Helicobacter pylori infection on
      gastric leptin expression to investigate the pathophysiological role of gastric
      leptin. METHODS: Surgically resected human stomach tissues were subjected to
      immunohistochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR)
      to check for the presence of leptin in the human gastric epithelium. A total of
      201 H pylori positive patients with chronic gastritis underwent eradication
      therapy for H pylori and were examined for the effect of infection cure in terms
      of body mass index (BMI) and serum leptin levels. Biopsy specimens from the
      gastric fundic mucosa were obtained from 40 of the 201 patients before and three
      months after eradication therapy. These samples were subjected to quantitative RT
      PCR to examine the effect of eradication therapy on leptin expression in the
      gastric fundic mucosa. RESULTS: Leptin immunoreactive cells were detected in the
      lower half of the gastric fundic glands and a leptin PCR product was also found
      in the gastric fundic mucosa. H pylori infection significantly increased gastric
      leptin expression. In addition, cure of H pylori infection significantly reduced
      gastric leptin expression, with a concomitant increase in BMI. In contrast, serum
      leptin levels did not change significantly after cure of H pylori infection.
      CONCLUSION: Leptin is present in the human gastric mucosa. Gastric leptin may
      play a role in weight gain after eradication of H pylori infection. Gastric
      leptin may have a local rather than systemic action.

PMID- 11511552
TI  - Helicobacter pylori infection prevents erosive reflux oesophagitis by decreasing
      gastric acid secretion.
AB  - BACKGROUND: Helicobacter pylori infection is less prevalent and atrophic
      gastritis is less extensive in patients with reflux oesophagitis than those
      without it, but few studies have examined this relationship directly. AIMS: We
      investigated the relationship between H pylori infection, acid secretion, and
      reflux oesophagitis in Japanese subjects. SUBJECTS: A total of 105 patients with
      erosive reflux oesophagitis were compared with 105 sex and age matched patients
      without reflux oesophagitis. METHODS: The diagnosis of H pylori infection was
      made by histological examination of gastric mucosal biopsy specimens, rapid
      urease test, and detection of serum IgG antibodies. Acid secretion was assessed
      by the endoscopic gastrin test. RESULTS: H pylori infection was present in 36
      patients with erosive reflux oesophagitis (34.3%) and in 80 control subjects
      (76.2%) (odds ratio 0.163, 95% confidence interval 0.09-0.29). Overall acid
      secretion was significantly greater in patients with reflux oesophagitis. Among H
      pylori positive patients, acid secretion was greater in patients with reflux
      oesophagitis than those without oesophagitis. CONCLUSION: In Japan, erosive
      reflux oesophagitis occurs most often in the absence of H pylori infection and
      gastric hyposecretion. Even in the presence of H pylori infection, reflux
      oesophagitis is more likely to develop in patients without gastric hyposecretion.
      H pylori infection may inhibit reflux oesophagitis by inducing hypoacidity.

PMID- 11511553
TI  - Inverse background of Helicobacter pylori antibody and pepsinogen in reflux
      oesophagitis compared with gastric cancer: analysis of 5732 Japanese subjects.
AB  - BACKGROUND: The relationship between Helicobacter pylori and reflux oesophagitis
      remains controversial. AIMS: To evaluate the relationship between H pylori and
      reflux oesophagitis in a large number of Japanese subjects. SUBJECTS: A total of
      5732 consecutive Japanese subjects during a health screening were enrolled.
      METHODS: Gastrointestinal endoscopy was performed on all subjects. We
      simultaneously measured serum anti-H pylori antibody and pepsinogen as markers of
      H pylori infection together with gastric atrophy. The risk of reflux oesophagitis
      was evaluated in relation to these markers, and the results were compared with
      those of gastric cancer. RESULTS: Reflux oesophagitis was found in 108 subjects.
      Both positivity for H pylori antibody (adjusted odds ratio (OR) 0.67 (95%
      confidence interval 0.45-1.0)) and "low" pepsinogen indicating gastric atrophy
      (OR 0.35 (0.18-0.68)) were negatively associated with reflux oesophagitis. After
      subjects were classified into four groups based on positivity or negativity for H
      pylori antibody and "low" pepsinogen, the prevalence of reflux oesophagitis
      showed a decreasing trend as H pylori induced gastric atrophy became more severe.
      The risk of gastric cancer showed an increasing trend, exactly the opposite to
      that of reflux oesophagitis. CONCLUSIONS: Analysis of a large series of Japanese
      subjects revealed a decreasing prevalence of reflux oesophagitis in conjunction
      with progress of gastric atrophy induced by H pylori infection. This pattern was
      completely opposite to that of gastric cancer cases. A protective role of H
      pylori for reflux oesophagitis through the development of gastric atrophy has
      been suggested.

PMID- 11511555
TI  - Gastric cancer and Helicobacter pylori: a combined analysis of 12 case control
      studies nested within prospective cohorts.
AB  - BACKGROUND: The magnitude of the association between Helicobacter pylori and
      incidence of gastric cancer is unclear. H pylori infection and the circulating
      antibody response can be lost with development of cancer; thus retrospective
      studies are subject to bias resulting from classification of cases as H pylori
      negative when they were infected in the past. AIMS: To combine data from all case
      control studies nested within prospective cohorts to assess more reliably the
      relative risk of gastric cancer associated with H pylori infection. To
      investigate variation in relative risk by age, sex, cancer type and subsite, and
      interval between blood sampling and cancer diagnosis. METHODS: Studies were
      eligible if blood samples for H pylori serology were collected before diagnosis
      of gastric cancer in cases. Identified published studies and two unpublished
      studies were included. Individual subject data were obtained for each. Matched
      odds ratios (ORs) and 95% confidence intervals (95% CI) were calculated for the
      association between H pylori and gastric cancer. RESULTS: Twelve studies with
      1228 gastric cancer cases were considered. The association with H pylori was
      restricted to non-cardia cancers (OR 3.0; 95% CI 2.3-3.8) and was stronger when
      blood samples for H pylori serology were collected 10+ years before cancer
      diagnosis (5.9; 3.4-10.3). H pylori infection was not associated with an altered
      overall risk of cardia cancer (1.0; 0.7-1.4). CONCLUSIONS: These results suggest
      that 5.9 is the best estimate of the relative risk of non-cardia cancer
      associated with H pylori infection and that H pylori does not increase the risk
      of cardia cancer. They also support the idea that when H pylori status is
      assessed close to cancer diagnosis, the magnitude of the non-cardia association
      may be underestimated.

PMID- 11511554
TI  - The significance of cagA(+) Helicobacter pylori in reflux oesophagitis.
AB  - BACKGROUND: Helicobacter pylori is a gastroduodenal pathogen associated with
      ulceration, dyspepsia, and adenocarcinoma. Recent preliminary studies have
      suggested that H pylori may be protective for oesophageal adenocarcinoma. In
      addition, strains of H pylori identified by the presence of the cytotoxin
      associated gene A (cagA) are shown to have a significant inverse association with
      oesophageal adenocarcinoma. Given that cagA(+) H pylori may protect against
      oesophageal carcinoma, these strains may be protective for oesophagitis, a
      precursor of oesophageal carcinoma. AIMS: The aim of this study was to
      investigate the association between cagA(+) H pylori and endoscopically proved
      oesophagitis. PATIENTS: The study group included 1486 patients attending for
      routine upper gastrointestinal tract endoscopy. METHODS: At endoscopy the
      oesophagus was assessed for evidence of reflux disease and graded according to
      standard protocols. Culture and histology of gastric biopsy specimens determined
      H pylori status. The prevalence of cagA was identified by an antibody specific
      ELISA (Viva Diagnostika, Germany). RESULTS: H pylori was present in 663/1485
      (45%) patients and in 120/312 (38%) patients with oesophagitis. Anti-CagA
      antibody was found in 499/640 (78%) H pylori positive patients. Similarly, anti
      CagA antibody was found in 422/521 (81%) patients with a normal oesophagus and in
      42/60 (70%) with mild, 24/35 (69%) with moderate, and 11/24 (46%) with severe
      oesophagitis. The risk of severe oesophagitis was significantly decreased for
      patients infected with cagA(+) H pylori after correction for confounding
      variables (odds ratio 0.57, 95% confidence interval 0.41-0.80; p=0.001).
      CONCLUSIONS: These results suggest that infection by cagA(+) H pylori may be
      protective for oesophageal disease.

PMID- 11511556
TI  - Prolonged measurement of lower oesophageal sphincter function in patients with
      intestinal metaplasia at the oesophagogastric junction.
AB  - BACKGROUND AND AIMS: It has been shown that gastro-oesophageal reflux plays a
      role in the pathogenesis of intestinal metaplasia (IM) limited to the
      oesophagogastric junction (OGJ), similar to the pathogenesis of IM in long
      segments of columnar lined oesophagus. The aim of this study was to examine lower
      oesophageal sphincter (LOS) function by means of prolonged recording in patients
      with IM limited to a normal appearing OGJ. PATIENTS AND METHODS: Eighteen
      patients with IM at the OGJ (five females, 13 males; mean age 55.4 years) and 22
      patients without IM (nine females, 13 males; mean age 53.9 years) underwent
      conventional stationary oesophageal manometry. Thereafter, seven hour water
      perfused manometry with simultaneous pH measurement (probe 5 cm proximal to the
      LOS) was performed. Swallowing was monitored with a pharyngeal sidehole and LOS
      pressure was recorded with a Dent sleeve. Patients were studied in the fasted
      state (three hours) and after a standardised meal (four hours). LOS pressure was
      analysed using customised software, and the incidence of reflux episodes (pH <4
      for at least five seconds) and transient LOS relaxations (TLOSRs) were examined.
      TLOSRs were judged to be accompanied by reflux if a decrease of 1 pH unit
      occurred during relaxation. RESULTS: Patients with IM at the OGJ had a higher
      prevalence of postprandial acid reflux compared with patients without IM. No
      differences were observed in LOS pressure (pre- and postprandially) or in the
      prevalence of TLOSRs. However, in the postprandial phase, the rate of TLOSRs
      accompanied by acid reflux was increased in patients with IM. CONCLUSION:
      Patients with IM at the OGJ have a higher prevalence of postprandial acid reflux.
      This is not associated with a higher prevalence of TLOSRs or a decreased LOS
      pressure but with a higher rate of TLOSRs accompanied by reflux.

PMID- 11511557
TI  - Bile reflux gastritis and Barrett's oesophagus: further evidence of a role for
      duodenogastro-oesophageal reflux?
AB  - BACKGROUND: There is increasing evidence that reflux of bile plays a part in the
      pathogenesis of Barrett's oesophagus. Bile injury to the gastric mucosa results
      in a "chemical" gastritis in which oedema and intestinal metaplasia are
      prominent. AIM: To determine if patients with Barrett's oesophagus have more bile
      related changes in antral mucosa than patients with uncomplicated gastro
      oesophageal reflux disease (GORD) or non-ulcer dyspepsia (NUD). PATIENTS AND
      METHODS: Patients were identified by a retrospective search of pathology records
      and those with a clinically confirmed diagnosis of either Barrett's oesophagus or
      reflux oesophagitis who had oesophageal and gastric biopsies taken at the same
      endoscopy and had no evidence of Helicobacter pylori infection entered the study.
      Control biopsies were taken from H pylori negative NUD patients. Antral biopsies
      were examined "blind" to clinical group and graded for a series of histological
      features from which the "reflux gastritis score" (RGS) and "bile reflux index"
      (BRI) could be calculated. The reproducibility of these histological scores was
      tested by a second pathologist. RESULTS: There were 100 patients with Barrett's,
      61 with GORD, and 50 with NUD. The RGSs did not differ between groups. BRI values
      in the Barrett's group were significantly higher than those in GORD subjects
      (p=0.014) which in turn were higher than those in NUD patients (p=0.037).
      Similarly, the frequency of high BRI values (>14) was significantly greater in
      the Barrett's group (29/100; 29%) than in the GORD (9/61; 14.8%) or NUD (4/50;
      8%) group. However, agreement on BRI values was "poor", indicating limited
      applicability of this approach. CONCLUSION: Patients with Barrett's oesophagus
      have more evidence of bile related gastritis than subjects with uncomplicated
      GORD or NUD. The presence of bile in the refluxate could be a factor in both the
      development of "specialised" intestinal metaplasia and malignancy in the
      oesophagus.

PMID- 11511558
TI  - Oxidative stress is more important than acid in the pathogenesis of reflux
      oesophagitis in rats.
AB  - BACKGROUND: Although antisecretory medications such as histamine type II receptor
      antagonists or proton pump inhibitors have been used to treat reflux
      oesophagitis, a considerable number of patients do not achieve complete mucosal
      healing or suffer from either sustained symptoms or ensuing complications,
      suggesting other damaging factors or impaired mucosal resistance are also
      involved in the pathogenesis of reflux oesophagitis. AIMS: The present study was
      designed to evaluate oxidative stress as the major pathogenic factor of reflux
      oesophagitis and to determine the usefulness of antioxidants in the treatment of
      reflux oesophagitis. MATERIALS AND METHODS: Reflux oesophagitis was induced by
      insertion of a 3 mm calibre ring into the duodenum, 1 cm distal to the ligament
      of Treitz, in Sprague-Dawley rats. RESULTS: DA-9601, a novel antioxidant
      substance, significantly attenuated the gross and histopathological scores of
      reflux oesophagitis compared with those treated with ranitidine alone or reflux
      oesophagitis controls in a dose dependent manner. Only scattered erosions were
      observed in the antioxidant pretreated group but acid suppression by ranitidine
      was not effective in decreasing the severity of reflux oesophagitis.
      Significantly increased amounts of malondialdehyde (MDA), increased nuclear
      factor kappaB (NFkappaB) activation, and depletion of reduced glutathione (GSH)
      were observed in experimentally induced reflux oesophagitis. DA-9601 pretreatment
      attenuated the decrement in mucosal GSH levels and decreased MDA formation
      significantly. DA-9601 treatment caused significant reductions in activation of
      NFkappaB transcription factor, especially the p50 subunit, in accordance with the
      significantly higher levels of inhibitory protein of NFkappaB expression.
      CONCLUSION: Reflux oesophagitis caused considerable levels of oxidative stress in
      the oesophageal mucosa and antioxidant treatment should be considered as
      supplementary therapy in the prevention or treatment of reflux oesophagitis with
      acid suppression.

PMID- 11511559
TI  - Drug treatments in upper gastrointestinal bleeding: value of endoscopic findings
      as surrogate end points.
AB  - INTRODUCTION: Pharmacotherapy for upper gastrointestinal bleeding has been
      difficult to evaluate because clinical end points are infrequent and affected by
      other factors. AIMS: To evaluate whether blood in the stomach at endoscopy
      reflected severity of bleeding, predicted clinical outcomes, and could be altered
      by therapeutic agents. METHODS: We studied 414 consecutive admissions with
      suspected upper gastrointestinal bleeding. Patients were randomised to receive
      lansoprazole 60 mg followed by 30 mg four times daily, tranexamic acid 2 g
      followed by 1 g four times daily, both drugs, or placebo for four days, until
      discharge or a clinical end point occurred. Logistic regression analysis was used
      to determine predictors of endoscopic changes and clinical outcomes, and to
      investigate the effects of drug treatments on blood in the stomach. RESULTS: Of
      414 patients with suspected upper gastrointestinal bleeding, 379 were endoscoped.
      Upper gastrointestinal bleeding was confirmed in 316. Sixteen required surgery
      within 30 days and 16 died on the index admission. Trial treatments were
      evaluable on a per protocol basis in 228 patients. The amount of blood in the
      stomach was found to reflect initial risk, with significant associations with
      high risk categorisation (odds ratio 3.7 (95% confidence interval 1.5-9.4) for
      more than a trace v none/trace), age (1.5 (1.1-1.9) per decade), and initial
      pulse (1.02 (1.00-1.04) per beat), and to predict rebleeding (9.2 (4.6-18.7)) and
      surgery (8.2 (2.9-22.9)). Other stigmata were less significant in these respects.
      The amount of blood in the stomach at endoscopy was reduced significantly by both
      lansoprazole (0.22 (0.07-0.63)) and tranexamic acid (0.27 (0.09-0.81)), although
      there was no evidence of synergy. CONCLUSIONS: Blood in the stomach reflects
      clinical features in patients with acute upper gastrointestinal bleeding and is
      reduced by treatment with lansoprazole and tranexamic acid.

PMID- 11511560
TI  - Intraepithelial and lamina propria lymphocytes show distinct patterns of
      apoptosis whereas both populations are active in Fas based cytotoxicity in
      coeliac disease.
AB  - BACKGROUND: Lamina propria (LPLs) and intraepithelial (IELs) lymphocytes are
      markedly increased in coeliac mucosa, and are thought to play a crucial role in
      the generation of villous atrophy in coeliac disease (CD). However, the
      mechanisms by which they mediate the killing of enterocytes in this condition are
      still poorly characterised. AIM: We investigated Fas mediated cytotoxicity and
      apoptosis of both LPLs and IELs, isolated from 10 untreated coeliac patients, 10
      coeliac patients on a gluten free diet, and 10 biopsied controls. METHODS: Fas
      and Fas ligand expression were assessed by flow cytometry and
      immunocytochemistry. Lymphocyte cytotoxicity against Fas expressing Jurkat cells
      was determined by the Jam test. The effect of the antagonist ZB4 anti-Fas
      antibody on apoptotic activity exerted by coeliac lymphocytes against enterocytes
      was analysed. Lymphocyte apoptosis was assessed by oligonucleosome ELISA.
      RESULTS: LPLs and IELs showed increased apoptotic activity and higher levels of
      Fas ligand expression in untreated CD compared with treated CD patients and
      controls. Enterocyte apoptosis observed after coculturing coeliac lymphocytes and
      enterocytes in the presence of ZB4 antibody was reduced. In active CD, LPLs
      manifested increased apoptosis whereas IELs showed decreased apoptosis.
      CONCLUSIONS: Our results support the involvement of the Fas/Fas ligand system in
      CD associated enterocyte apoptosis. Increased LPL apoptosis is likely to
      downregulate mucosal inflammation whereas decreased IEL apoptosis could be
      responsible for autoimmune and malignant complications of CD.

PMID- 11511561
TI  - Expression of nitric oxide synthases and effects of L-arginine and L-NMMA on
      nitric oxide production and fluid transport in collagenous colitis.
AB  - BACKGROUND AND AIMS: Luminal nitric oxide (NO) is greatly increased in the colon
      of patients with collagenous and ulcerative colitis. To define the source and
      consequence of enhanced NO production we have studied expression of NO synthase
      (NOS) isoforms and nitrotyrosine in mucosal biopsies from these patients. In
      addition, effects on colonic fluid transfer caused by manipulating the substrate
      of NOS were studied in patients with collagenous colitis. PATIENTS: Eight
      patients with collagenous colitis, nine with active ulcerative colitis, and 10
      with uninflamed bowel were included. METHODS: Expression of NOS isoforms was
      quantified by western blotting. Inducible NOS (iNOS) and nitrotyrosine were
      localised by immunohistochemistry. Modulation of NOS activity by topical N(G)
      monomethyl-L-arginine (L-NMMA) or L-arginine was assessed during perfusion of
      whole colon. Plasma and perfusate nitrite/nitrate (NOx) was measured by Griess'
      reaction. RESULTS: Both in collagenous and ulcerative colitis, expression of iNOS
      was 10(2)-10(3) higher (p<0.001) than in uninflamed bowel and localised primarily
      to the epithelium. Endothelial NOS was evenly expressed in all groups while
      neuronal NOS was undetectable. Nitrotyrosine was markedly expressed in active
      ulcerative colitis but rarely detected in collagenous colitis and never in
      uninflamed bowel. In collagenous colitis, the output of NOx was markedly
      increased compared with uninflamed bowel (283 (58) v <37 nmol/min; p<0.01) and
      fluid was net secreted. L-NMMA reduced the output of NOx by 13-66% (95%
      confidence intervals) and secretion of fluid by 25-109% whereas L-arginine
      increased the output of NOx by 3-39% and secretion of fluid by 15-93%.
      CONCLUSIONS: In collagenous colitis, as opposed to ulcerative colitis,
      upregulation of iNOS occurs in the absence of nitrotyrosine formation and mucosal
      damage. Excess generation of NO may be the primary cause of diarrhoea in this
      condition.

PMID- 11511562
TI  - Effects of a motilin receptor agonist (ABT-229) on upper gastrointestinal
      symptoms in type 1 diabetes mellitus: a randomised, double blind, placebo
      controlled trial.
AB  - INTRODUCTION: Erythromycin, a motilin agonist, is a potent prokinetic. ABT-229 is
      a specific motilin agonist that dose dependently accelerates gastric emptying.
      Dyspepsia and gastroparesis are common problems in type 1 diabetes mellitus. We
      aimed to evaluate the efficacy of ABT-229 in symptomatic diabetic patients with
      and without delayed gastric emptying. METHODS: Patients with type 1 diabetes and
      postprandial symptoms were randomised (n=270). Based on a validated C(13)
      octanoic acid breath test, patients were assigned to either the delayed or normal
      gastric emptying strata. Patients received one of four doses of ABT-229 (1.25,
      2.5, 5, or 10 mg twice daily before breakfast and dinner) or placebo for four
      weeks following a two week baseline. A self report questionnaire measured
      symptoms on visual analogue scales; the primary outcome was assessment of change
      in the total upper abdominal symptom severity score (range 0-800 mm) from
      baseline to the final visit. RESULTS: The treatment arms were similar regarding
      baseline characteristics. There was symptom improvement on placebo and a similar
      level of improvement on active therapy for the upper abdominal discomfort
      severity score (mean change from baseline -169, -101, -155, -143, and -138 mm for
      placebo, and 1.25, 2.5, 5, and 10 mg ABT-229, respectively, at four weeks by
      intent to treat). The results were not significantly different in those with and
      without delayed gastric emptying. The severity of bloating, postprandial nausea,
      epigastric discomfort, heartburn, and acid regurgitation worsened dose
      dependently in a greater number of patients receiving ABT-229 than placebo.
      Overall, 63% of patients on placebo reported a good or excellent global response,
      and this was not different from the active treatment arms. CONCLUSIONS: The
      motilin agonist ABT-229 was not efficacious in the relief of postprandial
      symptoms in diabetes mellitus in the presence or absence of delayed gastric
      emptying.

PMID- 11511563
TI  - Faecal calprotectin and faecal occult blood tests in the diagnosis of colorectal
      carcinoma and adenoma.
AB  - BACKGROUND AND AIMS: Testing for faecal occult blood has become an accepted
      technique of non-invasive screening for colorectal neoplasia but lack of
      sensitivity remains a problem. The aim of this study was to compare the
      sensitivity and specificity of faecal calprotectin and faecal occult blood in
      patients with colorectal cancer and colonic polyps. METHODS: Faecal calprotectin
      and occult blood were assessed in 62 patients with colorectal carcinoma and 233
      patients referred for colonoscopy. The range of normality for faecal calprotectin
      (0.5-10.5 mg/l) was determined from 96 healthy subjects. RESULTS: Median faecal
      calprotectin concentration in the 62 patients with colorectal carcinoma (101
      mg/l, 95% confidence interval (CI) 57-133) differed significantly from normal
      (2.3 mg/l, 95% CI 1.6-5.0) with 90% of patients having elevated levels (normal
      <10 mg/l) whereas only 36/62 (58%) had positive faecal occult bloods. There was
      no significant difference in faecal calprotectin levels when considering location
      or Dukes' staging of tumour. Percentage positivity of faecal occult bloods was
      significantly higher for Dukes' stage C and D cancers compared with Dukes' A and
      B. In the colonoscopy group, 29 patients with adenomatous polyps were detected in
      whom the median faecal calprotectin was 12 mg/l (95% CI 2.9-32). Sensitivity for
      detection of adenomatous polyps was 55% using the calprotectin method and 10%
      using faecal occult blood testing. The overall sensitivity and specificity of
      calprotectin for colorectal cancer and adenomatous polyps as a combined group was
      79% and 72%, respectively, compared with a sensitivity and specificity of faecal
      occult blood of 43% and 92%. CONCLUSIONS: Faecal calprotectin is a simple and
      sensitive non-invasive marker of colorectal cancer and adenomatous polyps. It is
      more sensitive than faecal occult blood tests for detection of colorectal
      neoplasia at the cost of a somewhat lower specificity.

PMID- 11511564
TI  - Overexpression of activin A in stage IV colorectal cancer.
AB  - BACKGROUND AND AIMS: Activins and inhibins are dimeric polypeptides that belong
      to the transforming growth factor beta (TGF-beta) superfamily and that bind to
      transmembrane receptors with serine/threonine kinase activity. The aim of this
      study was to characterise, in colon cancer cell lines and in normal and malignant
      human colon tissues, levels of expression of inhibin subunits that are involved
      in activin/inhibin dimer formation, and of the type I and II activin receptors
      (actRI and actRII). METHODS: Expression of inhibin subunits and activin receptors
      was analysed by northern blot analysis. Inhibin betaA and activin receptor
      expression were also assessed by use of polymerase chain reaction (PCR). In
      addition, activin A/inhibin betaA localisation in human colon samples was
      assessed by immunohistochemistry and in situ hybridisation. RESULTS: Inhibin
      betaA mRNA was expressed in CaCo2 cells but not in SW 837 or SW 1463 cells
      whereas inhibin betaB and inhibin alpha were below the level of detection. In
      contrast, all four activin receptors were present in the three cell lines. Colon
      cancers overexpressed inhibin betaA mRNA in comparison with normal colon, and
      this overexpression was greatest in stage IV tumours. ActRIb mRNA levels were
      slightly higher in the normal colon than in cancer tissues. By
      immunohistochemistry and in situ hybridisation, activin A and inhibin betaA mRNA
      were present in the mucosal epithelial cells in normal tissues from patients with
      stage I disease but were either absent or weakly present in normal tissues from
      patients with stage IV disease. Conversely, they were present at weak to moderate
      levels in stage I cancers but at high levels in stage IV cancers. CONCLUSIONS:
      Our findings indicate that activin A is overexpressed in human colorectal
      tumours, especially in stage IV disease, raising the possibility that activin A
      may have a role in advanced colorectal cancer.

PMID- 11511565
TI  - Increased rectal cell proliferation following alcohol abuse.
AB  - BACKGROUND: Epidemiological data indicate an increased risk for rectal cancer
      following chronic alcohol consumption. As chronic ethanol ingestion leads to
      rectal hyperregeneration in experimental animals, indicating a state of increased
      susceptibility to carcinogens, we studied cell proliferation in alcohol abusers.
      METHODS: Rectal biopsies were taken from 44 heavy drinkers and 26 controls. Cell
      proliferation, including proliferative compartment size, was measured by
      immunohistological staining for proliferative cell nuclear antigen (PCNA) and
      Ki67, and by in situ hybridisation for histone H3. Quantification of cell
      proliferation using PCNA staining was evaluated in 27 alcohol abusers and 12
      controls. In addition, immunohistology was performed for cytokeratins and gene
      products of Rb1, bcl-2, and p53. RESULTS: Heavy drinking resulted in increased
      cell proliferation of the rectal mucosa, as shown by increased detection of
      different proliferation markers. However, cell differentiation regarding
      cytokeratin expression patterns was unchanged as well as regulatory factors
      involved in carcinogenesis and/or apoptosis. CONCLUSION: Chronic alcohol abuse
      leads to rectal mucosal hyperproliferation in humans, a condition associated with
      an increased cancer risk.

PMID- 11511566
TI  - The natural course of hepatitis C virus infection after 22 years in a unique
      homogenous cohort: spontaneous viral clearance and chronic HCV infection.
AB  - BACKGROUND/AIMS: The cohort of Irish women infected with hepatitis C virus (HCV)
      genotype 1b via contaminated anti-D immunoglobulin in 1977 represent a unique
      homogenous group to investigate the natural course of HCV infection. METHODS: The
      clinical status of 87 polymerase chain reaction (PCR) positive and 68 PCR
      negative women was investigated at diagnosis (1994/95) and after 4-5 years of
      follow up (21/22 years after inoculation). Other features investigated included:
      histological status/progression, psychosocial impact of HCV infection,
      extrahepatic manifestations, and HLA class II associations. RESULTS: The most
      common symptoms reported were fatigue and arthralgia. Furthermore, 77% of women
      fell within the clinical range for psychological distress. A history of icteric
      hepatitis was reported in 20.6% of PCR negative and 3.4% of PCR positive women
      after inoculation (p=0.002). The mean histological activity index/fibrosis scores
      of PCR positive and negative women were 4.1 (1.4)/1.1 (1.3) and 2.1 (1.5)/0.15
      (0.36) at diagnosis and 4.1 (1.2)/1.0 (1.0) in 44 PCR positive women after five
      years of follow up. Cirrhosis or hepatocellular carcinoma was not observed. The
      DRB1*01 allele was present in 28.8% of PCR negative and 8.7% of PCR positive
      women (p=0.004). The prevalence rates of mixed cryoglobulinaemia, sicca complex,
      positive thyroid autoantibodies, antinuclear antibody, rheumatoid factor, and
      antimitochondrial antibody in PCR positive women were 12.7%, 7.6%, 13.9%, 5.1%,
      3.8%, and 3.8%. CONCLUSIONS: A benign course of HCV infection with lack of
      disease progression was observed in women with chronic HCV, 22 years after
      inoculation. Acute icteric hepatitis and the HLA DRB1*01 allele were associated
      with viral clearance. Despite this favourable outcome, high levels of
      psychological distress and poor quality of life were present.

PMID- 11511567
TI  - Outcome of liver disease in children with Alagille syndrome: a study of 163
      patients.
AB  - BACKGROUND AND AIMS: Various opinions have been expressed as to the long term
      prognosis of liver disease associated with Alagille syndrome (AGS). PATIENTS AND
      METHODS: We reviewed the outcome of 163 children with AGS and liver involvement,
      investigated from 1960 to 2000, the end point of the study (median age 10 years
      (range 2 months to 44 years)) being death, liver transplantation, or the last
      visit. RESULTS: At the study end point, of the 132 patients who presented with
      neonatal cholestatic jaundice, 102 remained jaundiced, 112 had poorly controlled
      pruritus, and 40 had xanthomas; cirrhosis was found in 35/76 livers, varices in
      25/71 patients, and liver transplantation had been carried out in 44 patients
      (33%). Forty eight patients died, 17 related to complications of liver disease.
      Of 31 patients who did not present with neonatal cholestatic jaundice, five were
      jaundiced at the study end point, 17 had well controlled pruritus, and none had
      xanthomas; cirrhosis was found in 6/18 patients, varices in 4/11, and none
      underwent liver transplantation. Nine patients died, two of liver disease. In the
      whole series, actuarial survival rates with native liver were 51% and 38% at 10
      and 20 years, respectively, and overall survival rates were 68% and 62%,
      respectively. Neonatal cholestatic jaundice was associated with poorer survival
      with native liver (p=0.0004). CONCLUSIONS: The prognosis of liver disease in AGS
      is worse in children who present with neonatal cholestatic jaundice. However,
      severe liver complications are possible even after late onset of liver disease,
      demanding follow up throughout life.

PMID- 11511568
TI  - Successful treatment with adefovir dipivoxil in a patient with fibrosing
      cholestatic hepatitis and lamivudine resistant hepatitis B virus.
AB  - Fibrosing cholestatic hepatitis (FCH) is a severe clinical and histological
      variant of hepatitis B virus (HBV) infection seen most commonly in the HBV
      infected allograft after liver transplantation. Without treatment, FCH is fatal,
      rapidly and universally. Remission has been reported with lamivudine but is
      associated with evolving resistance to lamivudine. Adefovir dipivoxil has
      recently been reported to be a potent and highly effective inhibitor of HBV
      replication in both wild-type and lamivudine resistant HBV infection. We report a
      case of FCH 15 months after liver transplantation for HBV related cirrhosis
      despite therapy with lamivudine and hepatitis B immunoglobulin (HBIg). Within two
      weeks of commencing treatment with adefovir dipivoxil 10 mg once daily, the
      patient had made a remarkable recovery with resolution of jaundice and
      normalisation of liver biochemistry. HBV DNA and hepatitis B e antigen were lost
      from serum subsequently and liver histology had improved at four months. This
      case report suggests firstly, that advanced FCH can be reversed and secondly,
      that addition of adefovir dipivoxil to lamivudine and HBIg may be an effective
      antiviral strategy.

PMID- 11511569
TI  - Drug therapy for portal hypertension.

PMID- 11511577
TI  - Alcohol--the changing face of a perennial problem.

PMID- 11511578
TI  - Climate change and health: information to counter the White House Effect.

PMID- 11511579
TI  - The Bush administration, the environment and public health-warnings from the
      first 100 days.

PMID- 11511570
TI  - Cyclooxygenase 2-implications on maintenance of gastric mucosal integrity and
      ulcer healing: controversial issues and perspectives.
AB  - Cyclooxygenase (COX), the key enzyme for synthesis of prostaglandins, exists in
      two isoforms (COX-1 and COX-2). COX-1 is constitutively expressed in the
      gastrointestinal tract in large quantities and has been suggested to maintain
      mucosal integrity through continuous generation of prostaglandins. COX-2 is
      induced predominantly during inflammation. On this premise selective COX-2
      inhibitors not affecting COX-1 in the gastrointestinal tract mucosa have been
      developed as gastrointestinal sparing anti-inflammatory drugs. They appear to be
      well tolerated by experimental animals and humans following acute and chronic
      (three or more months) administration. However, there is increasing evidence that
      COX-2 has a greater physiological role than merely mediating pain and
      inflammation. Thus gastric and intestinal lesions do not develop when COX-1 is
      inhibited but only when the activity of both COX-1 and COX-2 is suppressed.
      Selective COX-2 inhibitors delay the healing of experimental gastric ulcers to
      the same extent as non-COX-2 specific non-steroidal anti-inflammatory drugs
      (NSAIDs). Moreover, when given chronically to experimental animals, they can
      activate experimental colitis and cause intestinal perforation. The direct
      involvement of COX-2 in ulcer healing has been supported by observations that
      expression of COX-2 mRNA and protein is upregulated at the ulcer margin in a
      temporal and spatial relation to enhanced epithelial cell proliferation and
      increased expression of growth factors. Moreover, there is increasing evidence
      that upregulation of COX-2 mRNA and protein occurs during exposure of the gastric
      mucosa to noxious agents or to ischaemia-reperfusion. These observations support
      the concept that COX-2 represents (in addition to COX-1) a further line of
      defence for the gastrointestinal mucosa necessary for maintenance of mucosal
      integrity and ulcer healing.

PMID- 11511580
TI  - Epidemiology and the genetic basis of disease.

PMID- 11511581
TI  - Theories for social epidemiology in the 21st century: an ecosocial perspective.

PMID- 11511582
TI  - Death-rates in Great Britain and Sweden. Some general regularities and their
      significance.

PMID- 11511583
TI  - Commentary: the longitudinal perspective and cohort analysis.

PMID- 11511584
TI  - Commentary: 'the child is father of the man.' The relationship between child
      health and adult mortality in the 19th and 20th centuries.

PMID- 11511585
TI  - Commentary: William Ogilvy Kermack and the childhood origins of adult health and
      disease.

PMID- 11511586
TI  - Causation in epidemiology: a Socratic dialogue: Plato.

PMID- 11511587
TI  - Commentary: positivized epidemiology and the model of sufficient and component
      causes.

PMID- 11511588
TI  - Commentary: Coda--a Socratic dialogue: Plato.

PMID- 11511589
TI  - Structural adjustments and their impact on health and society: a perspective from
      Pakistan.

PMID- 11511590
TI  - Economic and health care restructuring--the need for better governance.

PMID- 11511591
TI  - The need for equity-oriented health sector reforms.

PMID- 11511592
TI  - Alcohol and coronary heart disease.
AB  - The data on two questions are reviewed: does heavy alcohol intake increase the
      risk of coronary heart disease (CHD)? And, is moderate intake protective?
      Identified alcoholics and problem drinkers have an increased risk of CHD, and in
      Britain there is a correlation among 22 towns, between the proportion of heavy
      drinkers in a town and CHD mortality. Of seven longitudinal studies reviewed, one
      shows heavy drinkers to have an increased CHD incidence. An inverse association
      between alcohol consumption and CHD mortality is seen in international
      comparisons and in time trends in the USA. Of six case-control studies reviewed
      from England and the USA, all show an inverse association between CHD and alcohol
      consumption which persists after control for other risk factors. Longitudinal
      studies, in Japanese-Americans, white American men and women, British civil
      servants, Puerto Ricans, Yugoslavs and Australians, all show moderate drinkers to
      have a lower CHD risk than abstainers. Abstainers are likely to differ from
      moderate drinkers in a number of ways. To date it has not proved possible to show
      that any of these differences account for the higher CHD risk of abstainers. The
      apparent protective effect is not large (RR = 0.5) but the consistency of the
      association and the existence of plausible mechanisms increase the likelihood
      that the negative association is causal. However, if alcohol intake were to
      increase in the population the social and medical consequences would be large. An
      increased intake is therefore not recommended as a community measure for CHD
      prevention.

PMID- 11511593
TI  - Commentary: reflections on alcohol and coronary heart disease.

PMID- 11511594
TI  - Commentary: alcohol, coronary heart disease and public health: which evidence
      based policy.

PMID- 11511595
TI  - Commentary: alcohol and coronary heart disease--laying the foundation for future
      work.

PMID- 11511596
TI  - Commentary: could abstinence from alcohol be hazardous to your health?

PMID- 11511597
TI  - Daily variations in deaths in Lithuania: the possible contribution of binge
      drinking.
AB  - BACKGROUND: During the early 1990s the countries of the Former Soviet Union
      experienced a dramatic rise in mortality, especially from cardiovascular
      diseases. Although still poorly understood there is evidence, particularly from
      Russia, that this mortality crisis is partly linked to alcohol consumption. In
      this paper we use data from Lithuania to explore the daily variations of deaths
      and the probable relationship with binge drinking. METHODS: Computerized death
      certificates for those aged 20-59 years were analysed according to the day of
      death, place of death, and cause of death for the years 1988-1997. RESULTS: There
      is a marked increase in deaths from accidents, violence, and alcohol poisoning at
      the weekend, suggesting a pattern of binge drinking in Lithuania. There is also a
      significant increase in ischaemic heart disease (IHD) deaths on Saturdays,
      Sundays and Mondays. If the analysis is performed separately according to place
      of death, the day of the week effect is strengthened for cardiovascular deaths
      outside of hospital; consistent with the idea of a sudden cardiac death.
      CONCLUSION: The increase in mortality from cardiovascular diseases observed at
      the weekend in Lithuania is similar to that observed in Moscow and other
      populations. The relationship with alcohol consumption is supported by the
      available physiological evidence. We propose that bingeing can be solely
      responsible for, or acts as a 'catalyst' for, pathophysiological events by
      increasing blood pressure, cardiac rhythm and coagulability. The increased IHD
      mortality observed throughout the weekend and on Monday in Lithuania may reflect
      the influence of alcohol consumption patterns in a population already subject to
      high psychosocial stress.

PMID- 11511598
TI  - Alcohol consumption and risk of prostate cancer: The Harvard Alumni Health Study.
AB  - BACKGROUND: Although many studies suggest that consumption of alcohol increases
      the risk of several site-specific cancers, the evidence remains unclear for
      prostate cancer. Few data exist on beverage-specific associations as well as
      lifetime patterns of alcohol consumption and prostate cancer risk. METHODS: We
      prospectively followed 7612 Harvard alumni (mean age 66.6 years) from 1988
      through 1993, during which 366 cases of incident prostate cancer occurred. Self
      reported alcohol consumption was assessed at baseline from wine, beer, and liquor
      intake. Previous assessments during college and in 1977 were also available.
      RESULTS: Overall, the mean total alcohol consumption in 1988 was 123.1 g/week, of
      which 28.6% was from wine, 15.8% from beer, and 55.6% from liquor. Compared to
      men reporting almost never drinking alcohol in 1988, the multivariate relative
      risks (95% CI) for 1 drink/month to < 3 drinks/week, 3 drinks/week to < 1 drink/
      day, 1 to < 3 drinks/day, and > or = 3 drinks/day were 1.33 (0.88-2.01), 1.65
      (1.12-2.44), 1.85 (1.29-2.64), and 1.33 (0.86-2.05), respectively. Wine or beer
      consumption was unassociated with prostate cancer; however, moderate liquor
      consumption was associated with a significant 61-67% increased risk of prostate
      cancer (P, non-linear trend < 0.001). Men initiating alcohol consumption between
      1977 and 1988 had a twofold increased risk of prostate cancer compared to men
      with almost no alcohol consumption at both times. CONCLUSIONS: In contrast to the
      majority of previous studies, we found a positive association between moderate
      alcohol consumption and the risk of prostate cancer. Liquor, but not wine or
      beer, consumption was positively associated with prostate cancer.

PMID- 11511599
TI  - Clusters within a general adult population of alcohol abstainers.
AB  - BACKGROUND: Our previous study found that alcohol abstainers use acute services
      more and preventative services less than safe level drinkers. The observed
      relationships between four categories of alcohol consumption and service use were
      J-shaped for acute services and inverted J-shaped for preventive services. The
      aim of this paper was to further investigate these relationships. METHODS: The
      design was a health and lifestyle survey of 41 000 randomly-sampled adults in SE
      England. The response rate was 60%. Distinctive subgroups within the alcohol
      abstainer group were investigated using cluster analysis, based on socio
      demographic and health status variables. Odds ratios for services use for the
      abstainer clusters, and three alcohol consumption groups were estimated from a
      logistic regression model which included age, social class, ethnic group,
      employment status, household composition, whether the respondent was a carer,
      smoking habit, use of private health insurance, and health status. RESULTS: Two
      clusters were formed for both males and females. Cluster 1 comprised, on average,
      older, frailer, and more disabled people. Cluster 2 comprised younger, healthier
      people, a greater proportion of whom belonged to ethnic minority groups. Cluster
      2 had similar rates of use of Accident & Emergency, GP, optician, and dental
      services compared with safe level drinkers. Cluster 1's rates differed from those
      of both Cluster 2 and safe level drinkers in almost all instances. CONCLUSIONS:
      The J- and inverted J-shaped relationships between alcohol consumption and
      service use are partly explained by a subgroup of abstainers who are older, of
      less good health, and who use hospital, clinic, and domiciliary healthcare
      services much more than safe level drinkers.

PMID- 11511600
TI  - Body weight, alcohol consumption and liver enzyme activity--a 4-year follow-up
      study.
AB  - BACKGROUND: This prospective study was performed in order to investigate the
      effect of baseline body mass index (BMI), BMI changes, baseline alcohol
      consumption, and changes in alcohol consumption on liver enzyme activity.
      METHODS: This study population consisted of 6846 male workers in a steel
      manufacturing company who had undergone health examinations in 1994 and 1998.
      RESULTS: The risk for elevated both aspartate aminotransferase (AST) and alanine
      aminotransferase (ALT) values over the four years increased with the baseline BMI
      and BMI changes, but not with alcohol consumption. Compared with the subject BMI
      < 20, the adjusted odds ratios (OR) for those with baseline BMI 20-21.9, 22-24.9,
      25- were 1.2, 1.6, 1.7 in AST and 1.4, 2.4, 2.8 in ALT, respectively. Compared
      with subjects who either lost or maintained their weight, the adjusted OR for men
      with slight, moderate, and heavy weight gain were 1.7, 2.6, 6.8 in AST and 2.4,
      3.9, 11.3 in ALT, respectively. However gamma-glutamyl transferase (GGT) was
      associated with BMI changes and baseline alcohol consumption, not with baseline
      BMI and changes in alcohol consumption. Compared with subjects who lost or
      maintained weight, the adjusted OR for men with slight, moderate, and heavy
      weight gain were 2.4, 4.4 and 8.5, respectively. In comparison with non-drinkers,
      the adjusted OR for light, moderate and heavy drinkers were 1.8, 2.1 and 5.8,
      respectively. CONCLUSION: These data suggest that body weight, rather than
      alcohol consumption, may be the major factor in determining the serum level of
      liver enzymes. Even when body weight was not generally considered to be
      overweight, slight to moderate gains in weight were associated with increases in
      serum liver enzymes.

PMID- 11511601
TI  - The economics of 'more research is needed'.
AB  - BACKGROUND: Results from epidemiology and other health research affect millions
      of life-years and billions of dollars, and the research directly consumes
      millions of dollars. Yet we do little to assess the value of research projects
      for future policy, even amid the ubiquitous assertions that 'more research is
      necessary' on a given topic. This methodological proposal outlines the arguments
      for why and how ex ante assessments can inform us about the value of a particular
      piece of further research on a topic. METHODS: Economics and decision theory
      concepts-cost-benefit analysis and probability-weighted predictions of outcomes
      allow us to calculate the payoff from applied health research based on resulting
      decisions. Starting with our probability distribution for the parameters of
      interest, a Monte Carlo simulation generates the distribution of outcomes from a
      particular new study. Each true value and outcome are associated with a policy
      decision, and improved decisions are valued to give us the study's contribution
      as applied research. RESULTS: The analysis demonstrates how to calculate the
      expected value of further research, for a simplified case, and assess whether it
      is really warranted. Perhaps more important, it points out what the measure of
      the value of a further study ought to be. CONCLUSIONS: It is quite possible to
      improve our technology for assessing the value of particular pieces of further
      research on a topic. However, this will only happen if the need and possibility
      are recognized by methodologists and applied researchers.

PMID- 11511602
TI  - Weight change, body weight and mortality: the impact of smoking and ill health.
AB  - OBJECTIVES: This paper examines the influence of cigarette smoking and ill health
      on the relationship between weight change, body weight and subsequent mortality
      to determine whether weight loss and leanness in middle to older age is
      deleterious to health. METHODS: Men aged 40-59 years at screening drawn from one
      general practice in each of 24 British towns, who completed a questionnaire 5
      years after screening (Q5) and provided full information on changes in weight and
      smoking status (n = 7065) were then followed up for an average of 13.8 years.
      RESULTS: In all men a shallow U-shaped relationship was seen between body mass
      index (BMI) at Q5 and all-cause mortality rates. Weight loss and substantial
      weight gain (> or =10%) were associated with increased mortality rates compared
      to the stable weight group. The increased risk associated with weight loss was
      seen in long- term non-smokers (n = 4101) and recent ex-smokers (n = 722) but not
      in current smokers (n = 2242) after adjustment for a wide range of potential
      confounders. However, the increased risk was markedly attenuated after exclusion
      of those with ill health (relative risk [RR] = 1.16, 95% CI : 0.84-1.59 and RR =
      0.79, 95% CI : 0.29-2.20 for long-term non-smokers and recent ex-smokers,
      respectively). Moderate weight gain (4-10%) was associated with lower risk of
      mortality than observed in those with stable weight but only in recent ex-smokers
      and in current smokers, not in long-term non-smokers. A positive association was
      seen between BMI at Q5 and all-cause mortality in non-smokers and this was
      strengthened by exclusion of men with weight loss. CONCLUSION: The increased risk
      of mortality associated with weight loss or low body weight in middle-aged and
      older men appears to be a direct consequence of ill health leading to weight loss
      and leanness. In healthy non-smoking men weight loss and leanness are not
      associated with increased mortality and moderate weight gain (4-10%) was neither
      deleterious nor beneficial.

PMID- 11511603
TI  - Are women more sensitive to smoking than men? Findings from the Renfrew and
      Paisley study.
AB  - BACKGROUND: Prescott et al. found that the relative risks associated with smoking
      for respiratory and vascular deaths were higher for women who inhale than for
      inhaling men, and found no gender differences in relative risks of smoking
      related cancers. The purpose of the present study was to assess whether these
      findings are reproducible, using data from the Renfrew and Paisley study.
      METHODS: Age-standardized mortality rate differences and age-adjusted mortality
      rate ratios (using Cox's proportional hazard model) were calculated for male and
      female smokers by amount smoked compared with never smokers. These analyses were
      repeated after excluding non-inhalers. RESULTS: The all-cause mortality rate
      ratio was higher for men than for women in all categories of amount smoked,
      although this difference was only statistically significant in the light smokers
      (1.83 [95% CI : 1.61-2.07] for men and 1.41 [95% CI : 1.28-1.56] for women, P =
      0.001). The cause-specific mortality rate ratios tended to be higher for men than
      for women, and this difference was most substantial for neoplasms (2.57 [95% CI :
      2.01-3.29] for male light smokers and 1.35 [95% CI : 1.14-1.61] for female light
      smokers, P < 0.001) and, in particular, for lung cancer (11.10 [95% CI : 5.89
      20.92] for male light smokers and 4.73 [95% CI : 2.99-7.50] for female light
      smokers, P = 0.03). Furthermore, looking at the rate differences the effects of
      smoking were uniformly greater in men than in women. These results were virtually
      unchanged after excluding non-inhalers. CONCLUSION: We found similar results to
      Prescott et al. when all smokers were considered, but could not reproduce their
      findings when non-inhalers were excluded. Given the fact that we showed greater
      rate differences in men than in women, we think that it is too early to conclude
      that women may be more sensitive than men to some of the deleterious effects of
      smoking.

PMID- 11511604
TI  - Commentary: tobacco-related diseases: a gender differential?

PMID- 11511605
TI  - Smokers for celibacy.

PMID- 11511606
TI  - Access to care and maternal mortality in Jamaican hospitals: 1993-1995.
AB  - BACKGROUND: As part of the reproductive health quality assurance programme, the
      Ministry of Health sought to review maternal deaths in public hospitals. These
      hospitals attend 95% of institutional births and 82% of all births. METHODS:
      Deaths among females 10-50 years in public hospitals during 1993-1995 were
      reviewed to identify pregnancy-related deaths. Cause of death and access to care
      were compared with previous studies (1981-1983 and 1986-1987 [12 months]).
      RESULTS: The maternal mortality ratio of 106.2 per 100 000 live births, was no
      different than the 119.7 observed in 1986-1987 and 118.6 for 1981-1983. The
      leading causes of death remained pre-eclampsia/eclampsia and haemorrhage. The
      only significant cause-specific decline occurred among deaths due to ruptured
      ectopic pregnancy (P = 0.012). While in 1986-1987 access to care was associated
      with risk of death from gestational hypertension (P = 0.02), these differences
      are no longer significant. Differences persist, however, for haemorrhage and all
      other causes, which were less likely to occur at the more skilled institutions.
      The region with the least obstetricians had the highest mortality ratio but the
      one with the most did not have the lowest ratio, indicating that quality is more
      important than quantity. CONCLUSIONS: Regional differences indicate the capacity
      to reduce maternal mortality by at least 50% with re-allocation of skilled
      personnel and improved quality. All hospitals must be able to manage haemorrhage
      cases as patients are unlikely to survive referral.

PMID- 11511607
TI  - Twinning rates and survival of twins in rural Nepal.
AB  - BACKGROUND: Twin pregnancies are common but there are few data on rates of
      twinning or survival of liveborn twin infants in developing countries. METHODS:
      The rates of multiple births were calculated in a population-based cohort of
      married women of childbearing age who were enrolled in a randomized community
      trial to assess the impact of vitamin A or beta-carotene on maternal and infant
      health and survival. RESULTS: The rate of twinning was 16.1 per 1000 pregnancies
      (7.4 if only twin pregnancies resulting in two liveborn infants were used). The
      rate for triplets and quadruplets was 0.19 and 0.06 per 1000 pregnancies.
      Twinning rates were higher among women of higher parity, but were not associated
      with maternal age. Twinning rates among twins where at least one was live born
      (or increased in utero survival) were 30% (95% CI : -1%, 71%) and 44% (95% CI :
      9%, 89%) higher among women receiving vitamin A and beta-carotene supplements
      than placebo, after adjusting for maternal age, gestational age, and parity. The
      perinatal mortality rate was 8.54 times higher for twins than singletons, 7.32
      higher for neonatal mortality, and 5.84 higher for cumulative 24-week mortality.
      This difference was reduced but not erased by adjusting for gestational age. No
      difference in survival of liveborn twin infants was seen by supplement group. A
      higher mortality rate among male twins was largely explained by gestational age.
      CONCLUSIONS: Multiple births are relatively common occurrences in rural Nepal,
      and carry a much higher mortality risk for the infants than for singletons.
      Vitamin A or beta-carotene supplementation appeared to increase the rate of
      twinning, or improve the survival of twins in utero, but did not increase twin
      survival after birth.

PMID- 11511608
TI  - Commentary: does use of food supplements influence the twin rate? New evidence
      from a randomized controlled trial.

PMID- 11511609
TI  - Socioeconomic status and lung cancer risk in Canada.
AB  - BACKGROUND: Several epidemiological studies have found that lung cancer is
      inversely related to socioeconomic status (SES) and suggest it as a possible risk
      factor for lung cancer. This study examines SES and lung cancer risk in Canada.
      METHODS: Mailed questionnaires with telephone follow-up were used to obtain data
      on 3280 newly diagnosed, histologically confirmed lung cancer cases and 5073
      population controls, between 1994 and 1997, in eight Canadian provinces.
      Measurement included information on SES, smoking habits, alcohol use, diet,
      residential and occupational histories and both residential and occupational
      exposure to environmental tobacco smoke (ETS). Odds ratios (OR) and 95% CI were
      derived from unconditional logistic regression analysis. RESULTS: Compared with
      high income adequacy, an increased risk was found among low income males and
      females, with adjusted OR of 1.7 (95% CI : 1.3-2.2) and 1.5 (95% CI : 1.1-2.0),
      respectively. Compared with < or = 8 years of education, the adjusted OR were 0.6
      (95% CI : 0.5-0.7) and 0.6 (95% CI : 0.5-0.8) for > or = 14 years education among
      males and females, respectively. Lung cancer risk was significantly increased for
      males of some social classes. The population attributable risk for income
      adequacy, education and social class was 24%, 25% and 21% among males,
      respectively, and 14% and 19% for income adequacy and education among females,
      respectively, in this Canadian population. CONCLUSIONS: A statistically
      significant association between income adequacy, education social class and lung
      cancer risk was found.

PMID- 11511610
TI  - Risk factors for non-Hodgkin's lymphoma according to family history of
      haematolymphoproliferative malignancies.
AB  - BACKGROUND: Aetiological profiles of non-Hodgkin's lymphoma (NHL) may differ
      depending upon whether the disease is inheritance-related or sporadic. Because
      familial risk (a probable surrogate of inheritance-relatedness) of NHL is
      influenced by haematolymphoproliferative malignancies (HLPM), we evaluated
      whether non-familial risk factors differ between NHL with and without a family
      history of HLPM, using the Selected Cancers Study data. METHODS: Cases were 1511
      men aged 31-59 and diagnosed with NHL during 1984-1988. Controls were men without
      NHL, frequency-matched to cases by age range and cancer registry (n = 1910).
      These groups were compared: cases with a family history of HLPM and without, and
      controls without such a family history. RESULTS: Polytomous logistic regression
      analyses showed that the odds ratio (OR) estimates of homosexual behaviour were
      18.2 (95% confidence interval (CI) : 4.8-69.4) and 5.6 (95% CI : 3.3-9.5) for NHL
      with and without a family history of HLPM, respectively. The corresponding
      estimates were 3.9 (95% CI : 1.7-8.9) and 2.2 (95% CI : 1.5-3.1) for history of
      enlarged lymph nodes. Variables only related to NHL with a family history were
      use of heroin (OR = 15.6, 95% CI : 3.4-70.4), exposure to a chlorinated
      hydrocarbon pesticide (OR = 2.3, 95% CI : 1.0-5.0), occupational exposure to
      plywood, fibreboard or particleboard (OR = 2.0, 95% CI : 1.2-3.4) and history of
      liver diseases (other than hepatitis or cirrhosis) (OR = 6.5, 95% CI : 1.2-36.2).
      The association between homosexual behaviour and NHL among men with a family
      history was stronger for those aged 31-44, especially for B-cell type of the
      disease. CONCLUSIONS: This study suggests differences in the risk factor profiles
      between NHL with and without a family history of HLPM. The higher risks of NHL
      for homosexual behaviour and heroin use, surrogates of HIV infection, in men with
      a family history of HLPM imply that genetic susceptibility may be influential on
      the occurrence of HIV-related NHL.

PMID- 11511612
TI  - Commentary: cancer in the air.

PMID- 11511611
TI  - Cancer incidence among Norwegian airline cabin attendants.
AB  - BACKGROUND: Cabin crews are exposed to cosmic radiation at work and this may
      increase their incidence of radiation-induced cancers. Former studies indicate an
      increased risk of breast cancer. METHODS: A retrospective cohort study was
      performed. The cohort was established from the files of the Civil Aviation
      Administration and included people with a valid licence as a cabin attendant
      between 1950 and 1994. The cohort was linked to the Cancer Registry of Norway.
      Observed number of cases was compared with expected, based on national rates.
      Breast cancer incidence was analysed, adjusting for individual fertility
      variables. RESULTS: A group of 3693 cabin attendants were followed over 72 804
      person-years. Among the women, 38 cases of breast cancer were observed
      (standardized incidence ratio (SIR) = 1.1, 95% CI : 0.8-1.5). Among men excess
      risks were found for cancers in the upper respiratory and gastric tract (SIR =
      6.0, 95% CI : 2.7-11.4) and cancer of the liver (two cases, SIR = 10.8, 95% CI :
      1.3-39.2). For both sexes elevated risks were found for malignant melanoma and
      non-melanoma skin cancer; for men these were SIR = 2.9 (95% CI : 1.1-6.4) and SIR
      = 9.9 (95% CI : 4.5-18.8) respectively, while for women these were SIR = 1.7 (95%
      CI : 1.0-2.7) and SIR = 2.9 (95% CI : 1.0-6.9) respectively. For no cancer site
      was a significant decreased risk found. CONCLUSIONS: An increased risk of
      radiation-induced cancers was not observed. The excess risks of some other
      cancers are more probably explained by factors related to lifestyle.

PMID- 11511613
TI  - Socioeconomic differences in behavioural and biological risk factors: a
      comparison of a Japanese and an English cohort of employed men.
AB  - BACKGROUND: To compare socioeconomic differences in behavioural and biological
      risk factors in Japanese and English 39-59-year-old employed men. METHODS: We
      measured systolic and diastolic blood pressure, total and high density
      lipoprotein (HDL) cholesterol, body mass index (BMI), waist-to-hip ratio and
      fibrinogen at medical screenings and smoking and alcohol consumption in health
      questionnaires among Japanese non-manual and manual employees of a steel products
      company and among English non-manual employees working in Civil Service
      departments. RESULTS: In England, higher employment grades were advantaged with
      regard to most risk factors studied. In Japan the picture was different in that
      higher grades had higher BMI, waist-to-hip-ratio and lower HDL cholesterol. In
      Japan employment grade differences in these three risk factors are clearly larger
      among younger men than among older men, while in England age differentials in the
      grade differences are small. Similar results were obtained for education.
      CONCLUSIONS: Important differences in the social patterning of risk factors were
      observed in our cohorts of employed Japanese and English men. The contribution
      that these risk factors make in explaining social differences in health may vary
      accordingly. Studies that identify the common and unique determinants of
      socioeconomic health differences in different populations are needed.

PMID- 11511614
TI  - A follow-up study of effects of chronic aircraft noise exposure on child stress
      responses and cognition.
AB  - BACKGROUND: Children are a high-risk group vulnerable to the effects of chronic
      aircraft noise exposure. This study examines the effects of aircraft noise
      exposure on children's health and cognition around London Heathrow airport and
      tests sustained attention as an underlying mechanism of effects of noise on
      reading and examines the way children adapt to continued exposure to aircraft
      noise. METHODS: In this repeated measures epidemiological field study, the
      cognitive performance and health of 275 children aged 8-11 years attending four
      schools in high aircraft noise areas (16-h outdoor Leq > 66 dBA) was compared
      with children attending four matched control schools exposed to lower levels of
      aircraft noise (16-h outdoor Leq < 57 dBA). The children first examined at
      baseline were examined again after a period of one year at follow-up. Health
      questionnaires and cognitive tests were group administered to the children in the
      schools. RESULTS AND CONCLUSIONS: At follow-up chronic aircraft noise exposure
      was associated with higher levels of annoyance and perceived stress, poorer
      reading comprehension and sustained attention, measured by standardized scales
      after adjustment for age, social deprivation and main language spoken. These
      results do not support the sustained attention hypothesis previously used to
      account for the effects of noise on cognition in children. The reading and
      annoyance effects do not habituate over a one-year period and do not provide
      strong evidence of adaptation.

PMID- 11511615
TI  - Lifestyle risk factors for lower limb venous reflux in the general population:
      Edinburgh Vein Study.
AB  - BACKGROUND: Varicose veins occur commonly in the general population but the
      aetiology is not well established. Varicosities are associated frequently with
      reflux of blood in the leg veins due to valvular incompetence. Our aim was to
      determine in the general population which lifestyle factors were related to
      reflux and thus implicated in the aetiology of varicose veins. METHODS: In the
      Edinburgh Vein Study, 1566 men and women aged 18-64 years were sampled randomly
      from the general population in the city of Edinburgh, Scotland, and had duplex
      scans to measure reflux in eight venous segments in each leg. A self-administered
      questionnaire enquired about occupation, mobility at work, smoking, obstetric
      history, dietary fibre intake and bowel habit. A bowel record form was completed
      subsequently. RESULTS: In women, venous reflux was associated with decreased
      sitting at work (odds ratio [OR] = 0.76, 95% CI : 0.61-0.94), previous pregnancy
      (OR = 1.20, 95% CI : 0.93-1.54), and a lower prior use of oral contraceptives (OR
      = 0.84, 95% CI : 0.66-1.06). Mean body mass index was greater in women with
      superficial reflux compared to those with no reflux: 26.2 kg/m(2) (95% CI : 25.5
      27.0) versus 25.2 kg/m(2) (95% CI : 24.8-25.6). On age adjustment, sitting at
      work remained related to reflux (OR = 0.78, 95% CI : 0.63-0.98) and prior use of
      oral contraceptives to superficial reflux (OR = 0.71, 95% CI : 0.50-1.01). In age
      adjusted analyses in men, height was related to reflux, (OR = 1.13, 95% CI : 1.02
      1.26) and straining at stool was related to superficial reflux (OR = 1.94, 95% CI
      : 1.12-3.35). No associations were found in either sex between reflux and social
      class, lifetime cigarette consumption, dietary fibre intake and intestinal
      transit time. CONCLUSIONS: This population study did not identify strong and
      consistent lifestyle risk factors for venous reflux although previous pregnancy,
      lower use of oral contraceptives, obesity and mobility at work in women and
      height and straining at stool in men may be implicated.

PMID- 11511616
TI  - Fetal exposure, heredity and risk indicators for cardiovascular disease in a
      Swedish welfare cohort.
AB  - BACKGROUND: The overall aim was to test whether low birthweight (LBW) in newborns
      is associated with the risk indicators for cardiovascular disease in early middle
      age, even in a welfare society. Further, a possible interaction of LBW and
      heredity for myocardial infarction or stroke was investigated. METHODS: Overall,
      subjects were identified as newborns in a local birth register, and as adult
      participants, in the Vasterbotten Intervention Program (n = 7876). Outcome
      measures such as systolic (SBP) and diastolic blood pressures (DBP), body mass
      index (BMI), cholesterol, triglycerides and anthropometrics were investigated (at
      age 29-41 years) in relation to LBW. RESULTS: Low birthweight was associated with
      increased SBP and DBP. Triglycerides were elevated among women with LBW and total
      cholesterol was elevated in men with LBW. Heredity for myocardial infarction or
      stroke interacted with LBW, and indicated a synergistic effect on the level of
      SBP. The BMI did not differ between LBW and normal birthweight subjects.
      CONCLUSIONS: Our interpretation is that the 'fetal origins' hypothesis' is valid
      for middle-age subjects who grow up in a welfare society. The population
      attributable proportions that result from different exposures to LBW were
      relatively small overall; from a public health perspective, heredity was more
      important than LBW for elevated SBP.

PMID- 11511617
TI  - Commentary: are birthweight and cardiovascular associations due to fetal
      programming?

PMID- 11511618
TI  - Incidence of primary opportunistic infections in two human immunodeficiency virus
      infected French clinical cohorts.
AB  - BACKGROUND: Clinical guidelines for the prevention of opportunistic infections in
      human immunodeficiency virus (HIV)-infected individuals have been developed on
      the basis of natural history data collected in the USA. The objective of this
      study was to estimate the incidence of primary opportunistic infections in HIV
      infected individuals in geographically distinct cohorts in France. METHODS: We
      conducted our study on 2664 HIV-infected patients from the Tourcoing AIDS
      Reference Centre and the hospital-based information system of the Groupe
      d'Epidemiologie Clinique du SIDA en Aquitaine enrolled from January 1987 to
      September 1995 and followed through December 1995. We estimated: (1) CD4-adjusted
      incidence rates of seven primary opportunistic infections in the absence of
      prophylaxis for that specific infection or any antiretroviral drugs other than
      zidovudine; and (2) CD4 lymphocyte count decline. RESULTS: The highest incidence
      rates for all opportunistic infections studied occurred in patients with CD4
      counts < 200/microl. With CD4 counts < 50/microl, the most common opportunistic
      infections were toxoplasmic encephalitis (12.6 per 100 person-years) and
      Pneumocystis carinii pneumonia (11.4 per 100 person-years). Mycobacterium
      tuberculosis was the least common opportunistic infection (< 5.0/100 person
      years). Even with CD4 counts > 300/microl, cases of Pneumocystis carinii
      pneumonia and toxoplasmic encephalitis were reported. The mean CD4 lymphocyte
      decline per month was 4.6 cells/microl. There was a significant association
      between HIV risk behaviour and the incidence of cytomegalovirus infection,
      between calendar year and the incidence of Pneumocystis carinii pneumonia,
      toxoplasmic encephalitis and Candida esophagitis, and between geographical area
      and the incidence of Pneumocystis carinii pneumonia and cytomegalovirus
      infection. CONCLUSIONS: Geographical differences exist in the incidence of HIV
      related opportunistic infections. These results can be used to define local
      priorities for prophylaxis of opportunistic infections.

PMID- 11511619
TI  - Seroepidemiological survey of hepatitis C virus among commercial sex workers and
      pregnant women in Kinshasa, Democratic Republic of Congo.
AB  - BACKGROUND: Studies conducted mainly in industrialized countries have shown that
      the transmission of hepatitis C virus (HCV) is mainly parenteral, and have
      emphasized the role of nosocomial transmission. In Equatorial Africa, the
      respective contributions of parenteral and non-parenteral routes of transmission
      are unknown. The potential role of sexual transmission in this area of high HCV
      endemicity, where sexually transmitted infections (STI) are frequent, is
      suggested by the fact that HCV infection is rare in infants and young
      adolescents, but increases thereafter with age. The present study, conducted in
      Democratic Republic of Congo, was designed to determine the prevalence of HCV
      infection and associated sexual risk factors in two female populations with
      different sexual behaviour. METHODS: Cross-sectional studies conducted among
      commercial sex workers (CSW; n = 1144) and pregnant women (n = 1092) in the late
      1980s in Kinshasa showed a high frequency of at-risk sexual behaviour, STI and
      human immunodeficiency virus (HIV) infection, particularly among CSW. We screened
      samples collected during these epidemiological studies for antibodies to HCV
      using a second-generation ELISA with confirmation by a third-generation LIA. We
      also assessed sociodemographic variables, medical history, STI markers and sexual
      behaviour, and their potential association with HCV infection. RESULTS: The
      overall prevalence of anti-HCV was 6.6% (95% CI : 5.2-8.2) among CSW and 4.3%
      (95% CI : 3.2-5.7) among pregnant women (age-adjusted OR = 1.5, 95% CI : 1.0-2.1,
      P = 0.05). Multivariate analysis showed that the presence of anti-HCV among CSW
      was independently associated with a previous history of blood transfusion (P <
      0.001), age >30 years (P < 0.001) and the presence of at least one biological
      marker of STI (P < 0.03). No such links were found among pregnant women (although
      the history of blood transfusions was not investigated in this group). Anti-HCV
      was not associated with sociodemographic variables or sexual behaviour in either
      group, or with individual markers of STI. Despite the high-risk sexual behaviour
      and the higher prevalence of STI in CSW, the difference in HCV seroprevalence
      between CSW and pregnant women (6.6% versus 4.3%) was small, particularly when
      compared with the difference in the seroprevalence of HIV (34.1% versus 2.8%).
      CONCLUSION: The role of sexual transmission in the spread of HCV seems to be
      limited. Parenteral transmission (including blood transfusion and injections),
      possibly related to the treatment of STI, probably plays a major role.

PMID- 11511620
TI  - Human immunodeficiency virus, hepatitis B, C and D in Bangladesh's trucking
      industry: prevalence and risk factors.
AB  - BACKGROUND: Human immunodeficiency virus (HIV) and hepatitis B and C, viral
      infections with shared percutaneous, mucosal and perinatal routes of
      transmission, are responsible for serious morbidity and mortality globally. In
      Bangladesh there is a dearth of research on prevalence and risk factors for these
      diseases. This study examines the prevalence of HIV and hepatitis (B, C, D) and
      risk factors associated with infection in men in Bangladesh's trucking industry
      (drivers and helpers on trucks), a population at risk for sexually transmitted
      infections. METHODS: The study population comprised 388 men (245 drivers, 143
      helpers) working out of Tejgaon truck stand in Dhaka, Bangladesh. Subjects were
      selected through a two-tiered sampling strategy. Of 185 trucking agencies 38 were
      randomly selected and a of 10 subjects was recruited from each agency. Subjects
      were interviewed, underwent a comprehensive physical examination and had blood
      samples taken. Gold standard laboratory tests were conducted to detect HIV,
      hepatitis B, C, and D infections. To assess risk factors associated with current
      hepatitis B infections or being a carrier (HBsAg) and lifetime exposure to
      hepatitis B infection (anti-HBc), simple and multiple logistic regression
      analyses were performed. RESULTS: The prevalence of diseases were: HIV 0%,
      hepatitis C <1%, hepatitis B surface antigen 5.9%, antibody to hepatitis B core
      antigen 48.1% (with 5 of the 23 HBsAg positive cases testing positive for HBeAg
      and 18 for anti-HBe), and hepatitis D 0%. Having ever received a therapeutic
      injection and having had relations with a commercial sex worker (CSW) in the past
      year were both significantly associated with lifetime exposure to hepatitis B
      (anti-HBc); having received a therapeutic injection in the past year was
      associated with being either currently infected with hepatitis B or a carrier
      (HBsAg). CONCLUSIONS: The results of the study illustrate the importance of
      educating health care practitioners about the dangers of unsterile injections,
      and of educating men in the trucking industry as well as their partners (CSW in
      particular) about the importance of condom use, especially in high-risk sexual
      contacts.

PMID- 11511621
TI  - Commentary: Human immunodeficiency virus and hepatitis in Bangladesh: widespread
      or targeted prevention strategies?

PMID- 11511622
TI  - Ageing with Trypanosoma cruzi infection in a community where the transmission has
      been interrupted: the Bambui Health and Ageing Study (BHAS).
AB  - BACKGROUND: The prevalence of Chagas' disease is decreasing in Brazil. Due to
      cohort effect, the disease might remain a public health problem for some time
      among older individuals. The present burden of Trypanosoma cruzi infection for
      the elderly living in areas where the transmission has been interrupted has not
      been studied. METHODS: The prevalence of T. cruzi infection and its association
      with indicators of health status and health services use were assessed among the
      elderly living in one of the oldest endemic areas in Brazil (Bambui, MG).
      Seropositivity was determined by blood tests (IHA and ELISA) performed in 85.6%
      of all residents aged 60+ (1496/1742) and in 83.1% of sampled residents aged 5-59
      years (1212/1458). RESULTS: Seropositivity showed a cohort effect, with no cases
      below 20 years and high prevalence among those aged 60+ years (37.7%). After
      adjustment for confounders, seropositivity was associated with self-rated health
      reasonable (OR = 1.43; 95% CI : 1.03-1.98) and bad/very bad (OR = 1.89; 95% CI :
      1.30-2.75), staying in bed in past 2 weeks (OR = 1.88; 95% CI : 1.21-2.92),
      hospitalization in past 12 months (OR = 1.41; 95% CI : 1.05-1.89) and use of 5+
      prescribed medications in past 3 months (OR = 1.75; 95% CI : 1.15-2.59).
      IMPLICATIONS: Our results are an example of how survival of individuals with past
      exposure to infectious disease may lead to a different picture of ageing in the
      developing world. Policy makers need to consider the extra burden imposed by
      increasing rates of non-infectious disease among the elderly (as observed in
      Brazil) including the consequences of T. cruzi infection in areas where the
      infection was widespread in the past.

PMID- 11511623
TI  - Commentary: Control of Chagas' disease: let's put people before vectors.

PMID- 11511624
TI  - Cardiopulmonary resuscitation performed in patients with terminal illness in
      Chiang Mai University Hospital, Thailand.
AB  - BACKGROUND: The original target of cardiopulmonary resuscitation (CPR) was
      victims of acute cardiopulmonary arrest. However, the use of CPR has expanded to
      a wide variety of patients including those with terminal illness for whom CPR is
      futile. The objective of this study was to identify the incidence of CPR
      performed, the severity of illness and the outcome of CPR attempted in terminal
      illness in a teaching hospital. METHODS: Cardiopulmonary resuscitation attempted
      in terminal illness was retrospectively assessed from the medical records of
      hospital deaths with any one of eight life-threatening diagnoses during a 3.5
      year period. RESULTS: Of 532 hospital deaths from terminal illness, 411 records
      (77.3%) were reviewed and abstracted. Most of the 411 patients had a low pre-CPR
      functional status. Generally, CPR was performed in 270 (65.7%) cases; 114 of
      those given CPR (42.2%) initially survived, but all died shortly after the
      manoeuvre. The high death rate following CPR may reflect both terminal illnesses
      and the severity of pre-event functional capacity of patients. CONCLUSION: The
      criteria for CPR in this group of patients need to be re-assessed and use of a
      Cerebral Performance Categories (CPC) score may be helpful.

PMID- 11511625
TI  - Historical roots of social epidemiology: socioeconomic gradients in health and
      contextual analysis.

PMID- 11511626
TI  - Preventing disability and death in old age.

PMID- 11511627
TI  - A compound catalytic model.

PMID- 11511632
TI  - A glance at child health.

PMID- 11511633
TI  - History in the public health tool kit.

PMID- 11511634
TI  - Vision of a rapid, flexible, cost effective, survey-based public health
      surveillance system.

PMID- 11511635
TI  - Health, equity, justice and globalisation: some lessons from the People's Health
      Assembly.

PMID- 11511636
TI  - Towards a more sustainable globalisation: the role of the public health
      community.

PMID- 11511637
TI  - A dialogue of the deaf? The health impacts of globalisation.

PMID- 11511638
TI  - Liberalisation, health and the World Trade Organisation.

PMID- 11511639
TI  - Glossary: healthy public policy.

PMID- 11511640
TI  - Psychosocial work characteristics and self rated health in four post-communist
      countries.
AB  - STUDY OBJECTIVES: To examine whether psychosocial factors at work are related to
      self rated health in post-communist countries. DESIGN AND SETTINGS: Random
      samples of men and women in five communities in four countries were sent a postal
      questionnaire (Poland, Czech Republic and Lithuania) or were invited to an
      interview (Hungary). Working subjects (n=3941) reported their self rated health
      in the past 12 months (5 point scale), their socioeconomic circumstances,
      perceived control over life, and the following aspects of the psychosocial work
      environment: job control, job demand, job variety, social support, and effort and
      reward at work (to calculate a ratio of effort/reward imbalance). As the results
      did not differ by country, pooled analyses were performed. Odds ratios of poor or
      very poor health ("poor health") were estimated for a 1 SD increase in the scores
      of work related factors. MAIN RESULTS: The overall prevalence of poor health was
      6% in men and 7% in women. After controlling for age, sex and community, all work
      related factors were associated with poor health (p<0.05). After further
      adjustment for perceived control, only two work related factors remained
      associated with poor health; the odds ratios (95% confidence intervals) for 1 SD
      increase in the effort/reward ratio (log transformed) and job variety were 1.51
      (1.29, 1.78) and 0.82 (0.73, 1.00), respectively. Further adjustment for all work
      related factors did not change these estimates. There were no interactions
      between individual work related factors, but the effects of job control and
      social support at work differed by marital status, and the odds ratio of job
      demand increased with increasing education. CONCLUSIONS: The continuous measure
      of effort/reward imbalance at work was a powerful determinant of self rated
      health in these post-communist populations. Although the cross sectional design
      does not allow firm conclusions as to causality, this study suggests that the
      effect of the psychosocial work environment is not confined to Western
      populations.

PMID- 11511641
TI  - Determinants of levels and changes of physical functioning in chronically ill
      persons: results from the GLOBE Study.
AB  - STUDY OBJECTIVE: Declines in physical functioning are a common result of chronic
      illness, but relatively little is known about factors not directly related to
      severity of disease that influence the occurrence of disability among chronically
      ill persons. The aim of this study was to assess the effect of a large number of
      potential determinants (sociodemographic factors, health related behaviour,
      structural living conditions, and psychosocial factors). DESIGN: Longitudinal
      study of levels and changes of physical functioning among persons suffering from
      four chronic diseases (asthma/chronic obstructive pulmonary disease (COPD), heart
      disease, diabetes, chronic low back pain). In 1991, persons suffering from one or
      more of these diseases were identified in a general population survey. Self
      reported disabilities, using a subset of the OECD disability indicator, were
      measured six times between 1991 and 1997. These data were analysed using
      generalised estimating equations, relating determinants measured in 1991 to
      disability between 1991 and 1997, and controlling for a number of potential
      confounders (age, gender, year of measurement, and type and severity of chronic
      disease). SETTING: Region of Eindhoven (south eastern Netherlands). PARTICIPANTS:
      1784 persons with asthma/COPD, heart disease, diabetes mellitus and/or low back
      pain. MAIN RESULTS: In a "repeated prevalence" model, statistically significant
      (p<0.05) and strong associations were found between most of the determinants and
      the prevalence of disabilities. In a "longitudinal change" model, statistically
      significant (p<0.05) predictors of unfavourable changes in physical functioning
      were low income and excessive alcohol consumption, while we also found
      indications for effects of marital status, degree of urbanisation, smoking, and
      external locus of control. CONCLUSIONS: Other factors than characteristics of the
      underlying disease have an important influence on levels and changes of physical
      functioning among chronically ill persons. Reduction of the prevalence of
      disabilities in the population not only depends on medical interventions, but may
      also require social interventions, health education, and psychological
      interventions among chronically ill persons.

PMID- 11511642
TI  - Gender inequalities in health among workers: the relation with family demands.
AB  - OBJECTIVES: To analyse whether there are gender inequalities in health among male
      and female workers who are married or cohabiting and to assess whether there are
      gender differences in the relation between family demands and health.
      Additionally, for both objectives it will be examined whether these gender
      patterns are similar for manual and non-manual workers. DESIGN AND SETTING: The
      data have been taken from the 1994 Catalonian Health Survey (CHS), a cross
      sectional survey based on a representative sample of the non-institutionalised
      population of Catalonia, a region in the north east of Spain that has about 6
      million inhabitants. The dependent variables were four ill health indicators
      (self perceived health status, limiting longstanding illness, having at least one
      chronic condition and mental health) and two health related behaviours closely
      related to having time for oneself (no leisure time physical activity and
      sleeping six hours or less a day). Family demands were measured with three
      variables: household size, living with children under 15 years and living with
      adults older than 65 years. The analysis was separated for gender and social
      class (manual and non-manual workers) and additionally adjusted for age. Gender
      differences for all dependent and independent variables were first tested at the
      bivariate level using the chi(2) test for categorical variables and the t test
      for age. Secondly, multivariate logistic regression models were fitted.
      PARTICIPANTS: Persons who were employed, married or cohabiting, aged 25 to 64
      years (2148 men and 1185 women). RESULTS: A female excess for all the ill health
      indicators was found, while there were no gender differences in the health
      related behaviours analysed. Family demands had a greater impact on health and
      health related behaviours of female manual workers. In this group household size
      was positively related to four dependent variables. The adjusted odds ratios
      (ORs) to living in family units of more than four persons versus living only with
      the spouse were 2.74 (95%CI=1.22, 6.17) for poor self perceived health status,
      3.16 (95%CI=0.98, 10.15) for limiting long standing illness, 3.28 (95%CI=1.45,
      7.44) for having at least one chronic condition, and 2.60 (95%CI=1.12, 6.00) for
      sleeping six hours or less a day. Among female manual workers living with
      children under 15 years was positively associated with no leisure time physical
      activity (adjusted OR=2.37; 95% CI=1.43, 3.92) and with sleeping six hours or
      less a day (adjusted OR=1.91; 95% CI=1.13, 3.32). Living with adults older than
      65 years had an unexpected negative relation with poor self perceived health
      status (adjusted OR=0.33; 95%CI=0.16, 0.66), and with chronic conditions
      (adjusted OR=0.45; 95%CI=0.24, 0.87) in female manual workers. Among male manual
      workers living with children under 15 years was positively associated with
      longstanding limiting illness (adjusted OR=2.44; 95%CI=1.36, 4.38). CONCLUSION:
      When gender differences in health are analysed, both the paid and the non-paid
      work should be considered as well as the interaction between these two
      dimensions, gender and social class. In Catalonia, as probably in Spain and in
      other countries, private changes such as sharing domestic responsibilities, as
      well as active public policies for facilitating family care are needed in order
      to reduce gender health inequalities attributable to the unequal distribution of
      family demands.

PMID- 11511643
TI  - Consumption of alcoholic beverages and subjective health in Spain.
AB  - STUDY OBJECTIVE: To examine the relation between alcohol and main alcoholic
      beverage consumption and subjective health in Spain. DESIGN: Logistic regression
      analysis using a cross sectional survey based on self reported data on alcohol
      and alcoholic beverage consumption, subjective health and the principal
      confounding factors (age, sex, civil status, educational level, job status,
      social support, region of residence, size of town or city, tobacco consumption,
      physical activity during leisure time and work hours, and chronic disease).
      SETTING: The 1993 Spanish National Health Survey. PARTICIPANTS: A 19 573 person
      sample, representative of the non-institutionalised Spanish population aged 16
      years and over. MAIN RESULTS: Among Spaniards, 31.4% reported their health as
      suboptimal (fair, poor or very poor) and 56.9% consumed alcohol regularly, with
      the majority having a preference for wine. Light (1-2 drinks per day) or moderate
      consumption (3-4 drinks per day) was the most frequent pattern. After adjusting
      for confounding factors, a negative dose-response relation was observed between
      consumption of total alcohol, wine and beer, and prevalence of suboptimal health
      (linear trend: p<0.001 for total alcohol, p=0.023 for wine, and p=0.030 for
      beer). In contrast, for consumption of spirits the prevalence of ill health in
      moderate drinkers was lower than in non-drinkers, with no clear relation at
      higher consumption. While persons reporting a preference for wine had a lower
      frequency of suboptimal health than did abstainers, they showed no difference in
      frequency of subjective ill health with respect to persons with preference for
      other types of drink or no preference whatsoever. CONCLUSIONS: The higher the
      consumption of total alcohol, wine and beer, the lower the prevalence of
      suboptimal health. These results differ from those obtained in several Nordic
      countries, where a "J shaped" relation has been observed for total alcohol and
      wine, and suggest that the relation between alcohol consumption and subjective
      health may be different in Mediterranean countries.

PMID- 11511644
TI  - The relation between questions indicating transient ischaemic attack and stroke
      in 20 years of follow up in men and women in the Renfrew/Paisley Study.
AB  - STUDY OBJECTIVE: Transient ischaemic attack (TIA) is often a precursor to stroke,
      so identification of people experiencing TIA could assist in stroke prevention by
      indicating those at high risk of stroke who would benefit most from intervention
      for other stroke risk factors. The objective of this study was to investigate
      whether answers to a simple questionnaire for TIA could predict the occurrence of
      stroke in the following 20 years. DESIGN: Prospective cohort study, conducted
      between 1972 and 1976, with 20 years of follow up. SETTING: Renfrew and Paisley,
      Scotland. PARTICIPANTS: 7052 men and 8354 women aged 45-64 years at the time of
      screening completed a questionnaire and attended a physical examination. The
      questionnaire asked participants if they had ever, without warning, suddenly lost
      the power of an arm, suddenly lost the power of a leg, suddenly been unable to
      speak properly or suddenly lost consciousness. These four questions were taken as
      indicators of TIA and were related to subsequent stroke mortality or hospital
      admission. MAIN RESULTS: For women, each question was significantly related to
      stroke risk, whereas for men only the question on loss of power of arm was
      significantly related to stroke risk. Men and women answering two or more
      questions positively had double the relative rate of stroke compared with men and
      women answering none of the questions positively, even after adjusting for other
      risk factors for stroke. CONCLUSIONS: A simple questionnaire for TIA could help
      predict stroke over 20 years of follow up. Targeting men and women who report TIA
      with early treatment could help to prevent strokes from occurring.

PMID- 11511645
TI  - Ethnicity, self reported psychiatric illness, and intake of psychotropic drugs in
      five ethnic groups in Sweden.
AB  - STUDY OBJECTIVE: This study hypothesises that the presumed increased risk of self
      reported longstanding psychiatric illness and intake of psychotropic drugs among
      Iranian, Chilean, Turkish, and Kurdish adults, when these groups are compared
      with Polish adults, can be explained by living alone, poor acculturation,
      unemployment, and low sense of coherence. DESIGN: Data from a national sample of
      immigrants/refugees, who were between the ages of 20-44 years old, upon their
      arrival in Sweden between 1980 and 1989. Unconditional logistic regression was
      used in the statistical modelling. SETTING: Sweden. PARTICIPANTS: 1059 female and
      921 male migrants from Iran, Chile, Turkey, Kurdistan and Poland and a random
      sample of 3001 Swedes, all between the ages of 27-60 years, were interviewed in
      1996 by Statistics Sweden. MAIN RESULTS: Compared with Swedes, all immigrants had
      an increased risk of self reported longstanding psychiatric illness and for
      intake of psychotropic drugs, with results for the Kurds being non-significant.
      Compared with Poles, Iranian and Chilean migrants had an increased risk of
      psychiatric illness, when seen in relation to a model in which adjustment was
      made for sex and age. The difference became non-significant for Chileans when
      marital status was taken into account. After including civil status and knowledge
      of the Swedish language, the increased risks for intake of psychotropic drugs for
      Chileans and Iranians disappeared. Living alone, poor knowledge of the Swedish
      language, non-employment, and low sense of coherence were strong risk factors for
      self reported longstanding psychiatric illness and for intake of psychotropic
      drugs. Iranian, Chilean, Turkish and Kurdish immigrants more frequently reported
      living in segregated neighbourhoods and having a greater desire to leave Sweden
      than their Polish counterparts. CONCLUSION: Evidence substantiates a strong
      association between ethnicity and self reported longstanding psychiatric illness,
      as well as intake of psychotropic drugs. This association is weakened by marital
      status, acculturation status, employment status, and sense of coherence.

PMID- 11511646
TI  - Sex specific difference in the relation between birth weight and arterial
      compliance in young adults: The Young Hearts Project.

PMID- 11511647
TI  - History of health, a valuable tool in public health.
AB  - The aim of this article is to highlight the importance of the history of public
      health for public health research and practice itself. After summarily reviewing
      the current great vitality of the history of collective health oriented
      initiatives, we explain three particular features of the historical vantage point
      in public health, namely the importance of the context, the relevance of a
      diachronic attitude and the critical perspective. In order to illustrate those
      three topics, we bring up examples taken from three centuries of fight against
      malaria, the so called "re-emerging diseases" and the 1918 influenza epidemic.
      The historical approach enriches our critical perception of the social effects of
      initiatives undertaken in the name of public health, shows the shortcomings of
      public health interventions based on single factors and asks for a wider time
      scope in the assessment of current problems. The use of a historical perspective
      to examine the plurality of determinants in any particular health condition will
      help to solve the longlasting debate on the primacy of individual versus
      population factors, which has been particularly intense in recent times.

PMID- 11511648
TI  - Measurement of self reported active exposure to cigarette smoke.
AB  - STUDY OBJECTIVE: The number of cigarettes smoked per day is an imprecise
      indicator of exposure to cigarette smoke, and biochemical assessment of exposure
      is not always feasible. The aim of this study was to develop more accurate
      measures of self reported active exposure to cigarette smoke. DESIGN: Mail survey
      in 386 smokers, retest at one month in 94 participants (24%), analysis of saliva
      cotinine in 98 participants (25%), collection of empty cigarette packs in 214
      participants (55%), collection of cigarette butts in 107 participants (28%). Ten
      questions and items intended to assess active exposure to cigarette smoke were
      tested and compared with saliva cotinine, the Fagerstrom test for nicotine
      dependence, and self rated dependence. SETTING: A population sample in Geneva,
      Switzerland, in 1999. PARTICIPANTS: 323 daily smokers and 63 occasional smokers.
      MAIN RESULTS: Measures that were associated with saliva cotinine included the
      number of cigarettes smoked per day (r(2)=0.36), smoking intensity (r(2)=0.40),
      the type of cigarettes smoked (regular versus light) (r(2)=0.04), smoking when
      ill (r(2)=0.15) and a single item rating of the total quantity of smoke inhaled
      (r(2)=0.27). A multivariate model combining the first four items explained the
      largest proportion of the variance in cotinine (r(2)=0.63), substantially more
      than was explained by the number of cigarettes per day alone, by 75% in all
      smokers and by 110% in daily smokers. CONCLUSIONS: The study identified measures
      of exposure to smoke that reflect saliva cotinine better than the number of
      cigarettes per day. These measures can be used in studies of the dose related
      risk of smoking and in smoking reduction studies.

PMID- 11511649
TI  - What determines drop out in prospective studies of coronary heart disease risk
      factors between youth and young adulthood: the Young Hearts Study.

PMID- 11511650
TI  - Setting up a specific surveillance system of community health during mass
      gatherings.

PMID- 11511651
TI  - Attitudes of parents towards measles and immunisation after a measles outbreak in
      an anthroposophical community.

PMID- 11511653
TI  - Polarization analysis in the crayfish visual system.
AB  - It is proposed that polarization sensitivity at the most peripheral stages of the
      crayfish visual system (lamina ganglionaris and medulla externa) is used to
      enhance contrast and thus may contribute to motion detection in low contrast
      environments. The four classes of visual interneurons that exhibit polarization
      sensitivity (lamina monopolar cells, tangential cells, sustaining fibers and
      dimming fibers) are not sensitive exclusively to polarized light but also respond
      to unpolarized contrast stimuli. Furthermore, many of these cells and the
      sustaining fibers in particular exhibit a greater differential e-vector
      responsiveness to a changing e-vector than to e-vector variations among steady
      state stimuli. While all four cell types respond modestly to light flashes at an
      e-vector of 90 degrees to the preferred orientation, the dynamic response to a
      changing e-vector is small or absent at this orientation. Because the sustaining
      fibers exhibit polarization sensitivity, and they provide afferent input to a
      subset of optomotor neurons, the latter were also tested for polarization
      sensitivity. The optomotor neurons involved in compensatory reflexes for body
      pitch were differentially sensitive to the e-vector angle of a flash of light,
      with maximum responses for e-vectors near the vertical. The motor neurons also
      exhibited a maximum response near the vertical e-vector to a continuously
      rotating polarizer. Two scenarios are described in which the sensitivity to a
      changing e-vector can produce motion responses in the absence of intensity
      contrast.

PMID- 11511654
TI  - Ocular filtering of ultraviolet radiation and the spectral spacing of
      photoreceptors benefit Von Kries colour constancy.
AB  - Ocular filters in the eyes of many vertebrates, including humans, absorb
      wavelengths shorter than approximately 400nm. These filters prevent the beta-band
      of a visual pigment from being exposed to ultraviolet radiation, essentially
      narrowing the spectral sensitivity of the different photoreceptor classes. A
      comparison of different hypothetical visual systems is used to show that von
      Kries colour constancy is improved by ocular filtration of ultraviolet radiation,
      whilst there is no reduction in colour discrimination. Furthermore, it is shown
      that the asymmetric spectral spacing of different photoreceptor classes present
      in the human visual system may benefit colour constancy. The results are
      interpreted in relation to predictions of von Kries colour constancy for a
      standard human observer.

PMID- 11511655
TI  - Functional mapping of ultraviolet photosensitivity during metamorphic transitions
      in a salmonid fish, Oncorhynchus mykiss.
AB  - Ultraviolet visual sensitivity appears to be reduced and, possibly, lost during
      smoltification in anadromous populations of salmonid fishes. Similar changes
      occur in non-anadromous salmonids over a mass range that is associated with
      smoltification in their anadromous conspecifics. However, in sexually mature
      adult salmonids, ultraviolet-sensitive cones are present in the dorso-temporal
      retina, suggesting that ultraviolet sensitivity (i) may be regained with sexual
      maturity or (ii) might never be completely lost. Both smoltification and the
      transition to sexual maturity are regulated, in part, by the hormone thyroxine.
      Thyroxine treatment of juvenile Oncorhynchus mykiss results in precocial
      developmental changes that mimic smoltification, including a reduction of
      ultraviolet sensitivity. However, whether loss of ultraviolet sensitivity in O.
      mykiss or in other species of salmonids is complete during normal development (or
      in response to thyroxine treatment) is unclear. In the present study, we have
      'mapped' topographically ultraviolet photosensitivity during natural and hormone
      induced smoltification. Thyroxine-treated O. mykiss juveniles and anadromous
      steelhead O. mykiss smolts were examined for ultraviolet visual sensitivity by
      recording compound action potentials from the optic nerve. By selectively
      illuminating either the dorsal or the ventral retina, we have shown that the
      reduction of ultraviolet sensitivity occurs primarily in the ventral retina in
      both groups of fish. Ultraviolet sensitivity remains intact in the dorsal retina.

PMID- 11511656
TI  - Foraging and prey-search behaviour of small juvenile rainbow trout (Oncorhynchus
      mykiss) under polarized light.
AB  - Several fish species appear to be polarization sensitive, i.e. to be able to
      discriminate a light source's maximum plane of polarization from any other plane.
      However, the functional significance of this ability remains unclear. We tested
      the hypothesis that polarized light improves the prey location ability of free
      swimming rainbow trout (Oncorhynchus mykiss) in laboratory aquaria. We found that
      prey location distances increased while the vertical component of prey location
      angle decreased under polarized compared with unpolarized (diffuse) illumination.
      The average frequency distribution of the horizontal component of prey location
      angle was more bimodal under polarized than unpolarized illumination. These
      results indicate that polarization sensitivity enhances prey location by juvenile
      rainbow trout.

PMID- 11511657
TI  - Spatial integration in polarization-sensitive interneurones of crickets: a survey
      of evidence, mechanisms and benefits.
AB  - Many insects exploit the polarization pattern of the sky for compass orientation
      in navigation or cruising-course control. Polarization-sensitive neurones (POL1
      neurones) in the polarization vision pathway of the cricket visual system have
      wide visual fields of approximately 60 degrees diameter, i.e. these neurones
      integrate information over a large area of the sky. This results from two
      different mechanisms. (i) Optical integration; polarization vision is mediated by
      a group of specialized ommatidia at the dorsal rim of the eye. These ommatidia
      lack screening pigment, contain a wide rhabdom and have poor lens optics. As a
      result, the angular sensitivity of the polarization-sensitive photoreceptors is
      very wide (median approximately 20 degrees ). (ii) Neural integration; each POL1
      neurone receives input from a large number of dorsal rim photoreceptors with
      diverging optical axes. Spatial integration in POL1-neurones acts as a spatial
      low-pass filter. It improves the quality of the celestial polarization signal by
      filtering out cloud-induced local disturbances in the polarization pattern and
      increases sensitivity.

PMID- 11511658
TI  - Microspectrophotometric measurements of vertebrate photoreceptors using CCD-based
      detection technology.
AB  - We have developed a charge-coupled-device (CCD)-based microspectrophotometer
      (MSP) system and provide the first report on the successful employment of this
      technology to measure the spectral absorbance properties of vertebrate
      photoreceptors. The principal difference between the CCD-based MSP system and
      wavelength-scanning MSP systems, commonly used in vision biology, is that a short
      duration (800-1200 ms), broad-spectrum flash is employed rather than ascending
      and descending wavelength scanning. Data acquisition is thus significantly
      faster, with the added possible advantages of less variance due to movement of
      target photoreceptors during measurement, reduced spectral distortion due to
      photoproduct interference and an ability to measure fast, transient changes in
      absorbance as bleaching proceeds. Rainbow trout photoreceptors, previously
      measured with a wavelength-scanning MSP system, were again measured using the CCD
      based MSP system. Our analysis of optical recordings from 102 photoreceptors
      corroborated data obtained previously with rainbow trout photoreceptors on
      lambda(max) (wavelength of maximum absorbance), A(max) (maximum absorbance) and
      half maximum bandwidth (HBW) of ultraviolet-, blue-, green- and red-sensitive
      cones and rods. There were slight differences in lambda(max) and half-maximum
      bandwidth of the ultraviolet-, blue- and green-sensitive cone classes, but this
      was most probably due to variation in the A(1):A(2) visual pigment ratio of the
      trout used in the two different studies. However, we were capable of resolving
      the A(1) and A(2) visual pigment spectra in the red-sensitive cones and the rods.

PMID- 11511659
TI  - Cone-based vision of rats for ultraviolet and visible lights.
AB  - Rats (Rattus norvegicus) have two classes of cone, one containing an ultraviolet
      (UV)-sensitive photopigment and the other housing a pigment maximally sensitive
      in the middle (M) wavelengths of the visible spectrum. The manner in which
      signals from these two cone types contribute to rat vision was investigated
      through recordings of a gross electrical potential (the electroretinogram, ERG)
      and behavioral discrimination tests. Spectral sensitivity functions obtained from
      both types of measurement indicate clear contributions from each of the cone
      classes, but there is a marked enhancement of the relative sensitivity to UV
      light in the behavioral index; for instance, under some photopic test conditions,
      rats are approximately equally sensitive to middle-wavelength and UV lights. In
      adaptation tests, thresholds for UV and M lights were found to be differentially
      elevated in the presence of chromatic adapting backgrounds, thus providing the
      possibility that signals from the two cones could be used by the rat visual
      system to support color discriminations. Evidence of dichromatic color vision in
      the rat was subsequently obtained from tests of wavelength discrimination.

PMID- 11511660
TI  - Host-plant-derived variation in ultraviolet wing patterns influences mate
      selection by male butterflies.
AB  - We report on the first case in which sequestered secondary plant compounds
      determine an insect's external appearance in the ultraviolet spectrum and thereby
      influence visually mediated mate choice. Larvae of the common blue butterfly
      Polyommatus icarus specifically sequester flavonoids in different amounts and
      types, depending on the part or species of food plant. During late pupal
      development the majority of ultraviolet-absorbing flavonoids are deposited in the
      wing scales. The flavonoid content of the larval diet thereby determines
      ultraviolet wing patterns. In laboratory and field experiments, male butterflies
      clearly preferred flavonoid-rich, ultraviolet-absorbing female dummies. This
      preference is mediated visually by the ultraviolet pattern of the wings. Food
      plant parts and species vary in value as a food source, so ultraviolet wing
      patterns may signal mate quality and are not a species-specific characteristic.
      We discuss the use of principal component analysis in analysing spectral data in
      the context of visual communication. We propose the alternative application of
      confidence intervals of averaged spectra as a novel straightforward statistical
      method for comparing groups of spectra in a manner that is independent of
      assumptions about the visual system of the receiver. In addition, they can be
      used to give confidence intervals to derived measures of colour such as quantum
      catch by photoreceptors.

PMID- 11511661
TI  - The linearly polarized light field in clear, tropical marine waters: spatial and
      temporal variation of light intensity, degree of polarization and e-vector angle.
AB  - Sensitivity to polarized light is widespread among marine animals, including
      crustaceans, cephalopods and some fishes. They use this ability to orient and
      find prey, and possibly for a number of other visual tasks. Unlike the
      ultraviolet-sensitive polarization receptors of most insects, the polarization
      receptors of marine invertebrates tend to be maximally sensitive near 500 nm,
      suggesting that polarized light in water differs from that in air. The underwater
      field of partially linearly polarized light has been studied for nearly 50 years,
      but data are still limited and sparse. We measured the submarine polarized light
      field from 350 to 600 nm throughout the day on a coral reef in the Florida Keys
      at a depth of 15m using the underwater laboratory Aquarius as a research
      platform. Our results show that the angle of polarization as viewed along any
      given line of sight at this depth is a relatively simple function of solar
      position and that the degree of polarization is greatest 60-90 degrees from the
      sun. Both e-vector angle and degree of polarization vary only slightly with
      wavelength, although light is sometimes less polarized in the ultraviolet. Since
      light is most intense at medium wavelengths and polarization is nearly maximal at
      these wavelengths, invertebrate polarization photoreceptors are spectrally well
      placed. Also, the relative spectral constancy of the angle and degree of
      polarization supports fish polarization sensitivity, which relies on spectrally
      diverse photoreceptor sets.

PMID- 11511662
TI  - Polarisation-dependent colour vision in Papilio butterflies.
AB  - Butterflies of the genus Papilio have polarisation-sensitive photoreceptors in
      all regions of the eye, and different spectral types of receptor are sensitive to
      different e-vector orientations. We have studied the consequences of this eye
      design for colour vision in behavioural tests and find that Papilio spp. see
      false colours due to the polarisation of light. They discriminate between
      vertically and horizontally polarised light of the same colour in the contexts of
      oviposition and feeding. The discrimination depends on the spectral composition
      of the stimuli. In the blue and probably in the green range, discrimination does
      not depend on intensity. However, colour discrimination is influenced by
      polarisation. Thus, colour and polarisation processing are not separated in the
      visual system of Papilio spp. From these results, we propose hypotheses about
      which photoreceptors contribute to colour vision in Papilio spp. and what
      adaptational value such a system might have for the butterflies. Finally, we give
      examples for other eyes that have a similar structure.

PMID- 11511663
TI  - Polarized light detection in spiders.
AB  - We describe here the detection of polarized light by the simple eyes of spiders.
      Using behavioural, morphological, electrophysiological and optical studies, we
      show that spiders have evolved two different mechanisms to resolve the e-vector
      of light. Wolf spiders (Lycosidae), are able to turn in response to rotation of a
      polarized pattern at the zenith of their visual fields, and we also describe a
      strip in the ventral retina of the principal (anterio-median) eyes that views
      this location and has receptors tiered into two layers. This provides each pair
      of receptors with a similar optical solution to that provided by the 'dorsal rim
      area' of the insect compound eye. In contrast, gnaphosid spiders have evolved a
      pair of lensless secondary eyes for the detection of polarized light. These two
      eyes, each sensitive to orthogonal directions of polarization, are perfectly
      designed to integrate signals from the larger part of the sky and cooperate to
      analyse the polarization of light. Built-in polarizers help to improve signal
      purity. Similar organisation in the eyes of several other spider families
      suggests that these two mechanisms are not restricted to only a few families.

PMID- 11511664
TI  - Avian ultraviolet vision and frequency-dependent seed preferences.
AB  - It is well established that ultraviolet sensitivity plays an important role in
      the visually guided behaviour of birds. From a foraging perspective, evidence now
      exists that ultraviolet wavelengths are used by birds when foraging for insects,
      berries, seeds and mammals. Here, we present the results of two laboratory
      experiments that test the effect of removing (i) ultraviolet wavelengths and (ii)
      wavebands in the human-visible region on the frequency-dependent seed preferences
      of zebra finches (Taeniopygia guttata). Although the seeds and backgrounds used
      in our experiments reflected mainly at long wavelengths, we found that removal of
      ultraviolet wavelengths significantly changed the strength and direction of
      frequency dependence compared with full-spectrum illumination. We also found that
      the removal of ultraviolet wavelengths (300-400 nm) did not affect the strength
      of frequency dependence compared with the removal of short wavelengths
      (approximately 400-500 nm), medium wavelengths (approximately 500-600 nm) or long
      wavelengths (approximately 600-700 nm). Since frequency-dependent selection has
      direct consequences for the stability of prey populations and the spectral
      quality of ambient light is known to vary considerably with climate, time of day
      and local habitat geometry, our results suggest that ultraviolet wavelengths
      might play an important role in the dynamics of plant populations. However, we
      urge caution about overestimating the importance of ultraviolet wavelengths
      compared with wavelengths in the human-visible spectrum.

PMID- 11511665
TI  - Is the ultraviolet waveband a special communication channel in avian mate choice?
AB  - There is growing evidence that ultraviolet (UV) wavelengths play an important
      role in avian mate choice. One of the first experiments to support this idea
      showed that female zebra finches (Taeniopygia guttata) prefer UV-reflecting males
      to males whose ultraviolet reflection has been removed. The effect was very
      strong despite little or no UV reflection from several plumage areas. However, it
      is not clear how the importance of the UV waveband compares to other regions of
      the bird-visible spectrum. We tested whether the response of female zebra finches
      to the removal of male UV reflection is greater than to the removal of other
      wavebands. We presented females with a choice of males whose appearance was
      manipulated using coloured filters. The filters removed single blocks of the
      avian visible spectrum corresponding closely to the spectral sensitivities of
      each of the zebra finch's single cone classes. This resulted in males that
      effectively had no UV (UV-), no short-wave (SW-), no medium-wave (MW-) or no long
      wave (LW-) plumage reflection. Females preferred UV- and SW- males. LW- and MW-
      males were least preferred, suggesting that female zebra finches show the
      greatest response to the removal of longer wavelengths. Quantal catches of the
      single cone types viewing body areas of the male zebra finch are presented for
      each treatment. Our study suggests it is important to consider the role of the UV
      waveband in avian mate choice in conjunction with the rest of the avian visible
      spectrum.

PMID- 11511666
TI  - The effects of the light environment on prey choice by zebra finches.
AB  - Recent research has highlighted the extent to which birds utilise ultraviolet
      vision in mate choice and foraging. However, neither the importance of the
      ultraviolet compared with other regions of the visual spectrum nor the use of
      wavelength cues in other visual tasks have been explored. We assessed the
      individual choices of zebra finches (Taeniopygia guttata) for different-coloured
      seeds (red and white millet) under lighting conditions in which filters
      selectively removed blocks of the avian-visible spectrum corresponding to the
      spectral sensitivity of the four retinal cone types that subserve colour vision
      in this species. The effects corresponded to those predicted from the calculated
      distances between seed types, and between each seed type and the background, in a
      simple model of tetrachromatic colour space. As predicted for this foraging task,
      the removal of long-wavelength information had a greater influence than the
      removal of shorter wavelengths, including ultraviolet wavelengths. These results
      have important implications for predator-prey interactions and suggest that
      future studies of natural foraging should consider variations in the light
      environment.

PMID- 11511667
TI  - Expression of pineal ultraviolet- and green-like opsins in the pineal organ and
      retina of teleosts.
AB  - In teleostean bony fishes, studies on the adults of various species have shown
      that pineal photoreceptors are maximally sensitive to short- and middle
      wavelength light, possibly utilising both rod-like and pineal-specific opsins.
      Until recently, however, very little was known about the pineal opsins present in
      embryonic and larval teleosts and their relationships to opsins expressed by
      retinal photoreceptors. Our immunocytochemical studies have revealed that, in
      Atlantic halibut, herring and cod, pineal photoreceptors express principal
      phototransduction molecules during embryonic life before they appear in retinal
      photoreceptors. In cDNA from embryonic and adult halibut, we identified two
      partial opsin gene sequences, HPO1 and HPO4, with highest homology to teleost
      green and ultraviolet cone opsins (72-83% and 71-83% amino acid identity,
      respectively). In halibut, these opsins are expressed in the pineal organ of
      embryos and appear in the retina of larvae. Our recent in situ hybridisation
      studies with RNA probes for HPO1 and HPO4 demonstrate the presence of green-like
      opsin mRNAs in the pineal organ and the retina of herring, cod, turbot, haddock,
      Atlantic salmon, zebrafish and three species of cichlid, and of ultraviolet
      opsins in the retinas of zebrafish, Atlantic salmon, turbot and the three cichlid
      species. We conclude that the halibut pineal organ appears to have the potential
      for both ultraviolet and green photosensitivity from the embryonic stage and that
      the retina may acquire the same potential during the larval stages. In the other
      teleosts studied, although both pineal and retinal photoreceptors seem to utilise
      a green-like opsin from the larval stage, ultraviolet photoreception appears to
      be restricted to the retina.

PMID- 11511668
TI  - Ultraviolet colour opponency in the turtle retina.
AB  - We have examined the functional architecture of the turtle Pseudemys scripta
      elegans retina with respect to colour processing, extending spectral stimulation
      into the ultraviolet, which has not been studied previously in the inner retina.
      We addressed two questions. (i) Is it possible to deduce the ultraviolet cone
      spectral sensitivity function through horizontal cell responses? (ii) Is there
      evidence for tetrachromatic neural mechanisms, i.e. UV/S response opponency?
      Using a constant response methodology we have isolated the ultraviolet cone input
      into the S/LM horizontal cell type and described it in fine detail. Monophasic
      (luminosity), biphasic L/M (red-green) and triphasic S/LM (yellow-blue)
      horizontal cells responded strongly to ultraviolet light. The blue-adapted
      spectral sensitivity function of a S/LM cell peaked in the ultraviolet and could
      be fitted to a porphyropsin cone template with a peak at 372 nm. In the inner
      retina eight different combinations of spectral opponency were found in the
      centre of the receptive field of ganglion cells. Among amacrine cells the only
      types found were UVSM-L+ and its reverse. One amacrine and four ganglion cells
      were also opponent in the receptive field surround. UV/S opponency, seen in three
      different types of ganglion cell, provides a neural basis for discrimination of
      ultraviolet colours. In conclusion, the results strongly suggest that there is an
      ultraviolet channel and a neural basis for tetrachromacy in the turtle retina.

PMID- 11511669
TI  - Influence of near-ultraviolet radiation on reproductive and immunological
      development in juvenile male Siberian hamsters.
AB  - The aim of this study was to characterize the lenticular ultraviolet transmission
      of the Siberian hamster (Phodopus sungorus) and to probe the range of near
      ultraviolet (UV-A, 315-400 nm) and visible wavelengths (400-760 nm) for
      modulating the photoperiodic regulation of its reproductive and immune systems.
      Ocular lenses from adult hamsters were found to transmit UV-A wavelengths at
      similar levels to visible wavelengths, with a short-wavelength cut-off of 300 nm.
      Five separate studies compared the responses of juvenile male hamsters to long
      photoperiods (16 h:8 h L:D), short photoperiods (10 h:14 h L:D) and short
      photoperiods interrupted by an equal photon pulse of monochromatic light of 320,
      340, 360, 500 or 725 nm during the night. The results show that UV-A wavelengths
      at 320, 340 and 360 nm can regulate both reproductive and immune short
      photoperiod responses as effectively as visible monochromatic light at 500 nm. In
      contrast, long-wavelength visible light at 725 nm did not block the short
      photoperiod responses. These results suggest that both wavelengths in the visible
      spectrum, together with UV-A wavelengths, contribute to hamster photoperiodism in
      natural habitats.

PMID- 11511670
TI  - The role of extraocular photoreceptors in newt magnetic compass orientation:
      parallels between light-dependent magnetoreception and polarized light detection
      in vertebrates.
AB  - Theoretical models implicating specialized photoreceptors in the detection of the
      geomagnetic field have been the impetus for studying the effects of light on
      magnetic compass orientation. Magnetic orientation in flies, amphibians and birds
      has been found to be influenced by light, and in all these groups a shift of
      approximately 90 degrees in the direction of magnetic compass orientation has
      been observed under certain wavelengths and/or intensities of light. In the
      eastern red-spotted newt Notophthalmus viridescens, wavelength-dependent effects
      of light on magnetic compass orientation appear to result from an antagonistic
      interaction between short-wavelength (< or = 450 nm) and long-wavelength (> or =
      500 nm) photoreception mechanisms. We have demonstrated that at least the short
      wavelength input to the newt's magnetic compass is mediated by extraocular
      photoreceptors located in or near the pineal organ, and here we present new
      findings that indicate that the putative long-wavelength mechanism is also
      associated with pineal photoreceptors. Interestingly, the amphibian pineal organ
      mediates orientation to both the e-vector of plane-polarized light and the
      magnetic field. Although the wavelength-dependence of the polarized light
      orientation in amphibians has not been studied, polarization sensitivity in
      fishes appears to be mediated by two antagonistic photoreception mechanisms that
      have similar spectral characteristics to those of the newts' magnetic compass
      response. These parallels, along with similarities in the types of receptors that
      are expected to be involved in light-dependent magnetoreception and polarized
      light detection, suggest that similar photoreception mechanisms may mediate the
      light-dependent magnetic and polarized light compasses.

PMID- 11511671
TI  - Topography of different photoreceptor cell types in the larval retina of Atlantic
      halibut (Hippoglossus hippoglossus).
AB  - The identities of single cone cells in the retina of Atlantic halibut
      (Hippoglossus hippoglossus) larvae were studied by in situ hybridisation using
      RNA probes for the five different halibut opsins. Four different cone opsins
      (ultraviolet-, blue-, green- and red-sensitive) are expressed in Atlantic halibut
      at the end of the yolk-sac period, whereas rod opsin is expressed later in
      development. Photoreceptor cells expressing ultraviolet-sensitive opsin are found
      only in the ventral retina, presumably to optimise detection of the downwelling
      ultraviolet light. The majority of the photoreceptors (approximately 90%) in the
      retina express green-sensitive opsin and its distribution shows no regional
      differences. In contrast, blue- and red-sensitive opsins are expressed much less
      frequently (in approximately 10% of photoreceptors), although these two opsins
      are also found over the entire retina. The expression patterns of the different
      visual pigments indicate some form of mosaic expression in the single-coned
      larval retina, and this is reminiscent of the square mosaic expression found in
      post-metamorphic Atlantic halibut. These findings suggest plasticity in green
      opsin-expressing cells during development, resulting in a square mosaic
      expression pattern.

PMID- 11511672
TI  - Signals from 'crabworld': cuticular reflections in a fiddler crab colony.
AB  - Fiddler crabs inhabit intertidal sand- and mudflats, where they live in dense
      colonies and are active on the surface during low tide. They exhibit a rich
      behavioural repertoire, with frequent interactions between animals in the context
      of territorial and mating activities. Male fiddler crabs have one massively
      enlarged and conspicuously coloured claw, which they use in waving displays and
      in fights with other males. The crabs carry their eyes on long, vertically
      oriented stalks high above the body and, as a consequence, see the bodies of
      conspecifics in the ventral visual field, below the local visual horizon, and
      against the mudflat surface as background. We filmed events in a colony of Uca
      vomeris with a normal video camera and an ultraviolet-sensitive camera placed at
      the eye height of an average crab, approximately 2-3 cm above ground. We also
      used a spectrographic imager and linear polarized filters to analyse the cues
      potentially available to the animals for detecting, monitoring and possibly
      identifying each other. Areas of high contrast in mudflat scenes include specular
      reflections on the wet cuticle of crabs that are horizontally polarised. Besides
      specular reflections, some parts of the cuticle generate high-contrast signals
      against the mudflat background, both at wavelengths between 400 and 700 nm, and
      in the ultraviolet region between 300 and 400 nm. Uca vomeris can be very
      colourful: the different parts of the large claw of the male are white, orange or
      red. The carapace colours of both males and females can range from a mottled
      yellowish green brown, to a brilliant light blue. White and blue colours contrast
      starkly with the mudflat background, especially in the ultraviolet wavelengths.
      Under stress, the blue and white colours can change within minutes to a duller
      and darker blue or to a dull white.

PMID- 11511673
TI  - Limits to the salience of ultraviolet: lessons from colour vision in bees and
      birds.
AB  - Ultraviolet is an important component of the photic environment. It is used by a
      wide variety of animals and plants in mutualistic communication, especially in
      insect and flower inter-relationships. Ultraviolet reflections and sensitivity
      are also becoming well considered in the relationships between vertebrates and
      their environment. The relative importance of ultraviolet vis a vis other primary
      colours in trichromatic or tetrachromatic colour spaces is discussed, and it is
      concluded that ultraviolet is, in most cases, no more important that blue, green
      or red reflections. Some animals may use specific wavebands of light for specific
      reactions, such as ultraviolet in escape or in the detection of polarised light,
      and other wavebands in stimulating feeding, oviposition or mating. When colour
      vision and, thus, the input from more than a single spectral receptor type are
      concerned, we point out that even basic predictions of signal conspicuousness
      require knowledge of the neuronal wiring used to evaluate the signals from all
      receptor types, including the ultraviolet. Evolutionary analyses suggest that, at
      least in arthropods, ultraviolet sensitivity is phylogenetically ancient and
      undergoes comparatively little evolutionary fine-tuning. Increasing amounts of
      ultraviolet in the photic environment, as caused by the decline of ozone in the
      atmosphere, are not likely to affect colour vision. However, a case for which
      ultraviolet is possibly unique is in the colour constancy of bees. Theoretical
      models predict that bees will perform poorly at identifying pure ultraviolet
      signals under conditions of changing illumination, which may explain the near
      absence of pure ultraviolet-reflecting flowers in nature.

PMID- 11511674
TI  - Visual pigments in the early life stages of Pacific northwest marine fishes.
AB  - Microspectrophotometry was used to measure the visual pigments in the rods and
      cones of 22 species of marine fish larvae netted from the surface waters off
      Friday Harbor Laboratories, Washington, USA. 13 species had rods, 12 of which
      contained visual pigments with a wavelength of maximum absorbance near 500 nm,
      while one, the sand lance (Ammodytes hexapterus), had its absorbance maximum at
      482 nm. The 22 species of fish larvae possessed varied combinations of single,
      double and twin cones, ranging in peak absorbance from 353 nm to 584 nm. Of
      these, green-sensitive single cones were present in 20 of the 22 species, and
      were the dominant cone type. Double and twin cones were present in 13 of the
      species. Most common were identical green-sensitive (twin) cones (in 11 species).
      Green/yellow-sensitive double cones occurred in four species. In a single
      instance (Hemilepidotus hemilepidotus) twin blue-sensitive, twin green-sensitive
      and double blue/yellow-sensitive cones were recorded. Of particular interest was
      the finding that 18 of the species had ultraviolet- and/or violet-absorbing
      single cones. It has been suggested that short-wavelength photosensitivity may be
      beneficial for planktivory by extending the spectral range over which vision can
      occur. The high percentage (82%) of ultraviolet and violet visual pigments in
      Pacific northwest fish larvae supports the prediction that short-wavelength
      sensitivity may be common in marine fish larvae.

PMID- 11511675
TI  - Polarization vision--a uniform sensory capacity?
AB  - In this concept paper, three scenarios are described in which animals make use of
      polarized light: the underwater world, the water surface and the terrestrial
      habitat vaulted by the pattern of polarized light in the sky. Within these
      various visual environments, polarized light is used in a number of ways that
      make quite different demands on the neural circuitries mediating these different
      types of behaviour. Apart from some common receptor and pre-processing
      mechanisms, the underlying neural mechanisms may differ accordingly. Often,
      information about chi (the angle of polarization), d (the degree of polarization)
      and lambda (the spectral content) might not --and need not--be disentangled.
      Hence, the hypothesis entertained in this account is that polarization vision
      comes in various guises, and that the answer to the question posed in the title
      is most probably no.

PMID- 11511676
TI  - EnVision+, a new dextran polymer-based signal enhancement technique for in situ
      hybridization (ISH).
AB  - Seventy paraffin-embedded cervical biopsy specimens and condylomata were tested
      for the presence of human papillomavirus (HPV) by conventional in situ
      hybridization (ISH) and ISH with subsequent signal amplification. Signal
      amplification was performed either by a commercial biotinyl-tyramide-based
      detection system [GenPoint (GP)] or by the novel two-layer dextran polymer
      visualization system EnVision+ (EV), in which both EV-horseradish peroxidase (EV
      HRP) and EV-alkaline phosphatase (EV-AP) were applied. We could demonstrate for
      the first time, that EV in combination with preceding ISH results in a
      considerable increase in signal intensity and sensitivity without loss of
      specificity compared to conventional ISH. Compared to GP, EV revealed a somewhat
      lower sensitivity, as measured by determination of the integrated optical density
      (IOD) of the positively stained cells. However, EV is easier to perform, requires
      a shorter assay time, and does not raise the background problems that may be
      encountered with biotinyl-tyramide-based amplification systems. (J Histochem
      Cytochem 49:1067-1071, 2001)

PMID- 11511677
TI  - Computerized image analysis as a tool to quantify infiltrating leukocytes: a
      comparison between high- and low-magnification images.
AB  - The purpose of the present study was to establish a rapid and reproducible method
      for quantification of tissue-infiltrating leukocytes using computerized image
      analysis. To achieve this, the staining procedure, the image acquisition, and the
      image analysis method were optimized. Because of the adaptive features of the
      human eye, computerized image analysis is more sensitive to variations in
      staining compared with manual image analysis. To minimize variations in staining,
      an automated immunostainer was used. With a digital scanner camera, low
      magnification images could be sampled at high resolution, thus making it possible
      to analyze larger tissue sections. Image analysis was performed by color
      thresholding of the digital images based on values of hue, saturation, and
      intensity color mode, which we consider superior to the red, green, and blue
      color mode for analysis of most histological stains. To evaluate the method, we
      compared computerized analysis of images with a x100 or a x12.5 magnification to
      assess leukocytes infiltrating rat brain tumors after peripheral immunizations
      with tumor cells genetically modified to express rat interferon-gamma (IFN-gamma)
      or medium controls. The results generated by both methods correlated well and did
      not show any significant differences. The method allows efficient and
      reproducible processing of large tissue sections that is less time-consuming than
      conventional methods and can be performed with standard equipment and software.(J
      Histochem Cytochem 49:1073-1079, 2001)

PMID- 11511678
TI  - Immunohistochemical localization of Pax2 and associated proteins in the
      developing kidney of mice with renal hypoplasia.
AB  - Pax2 has been identified as a key regulatory protein associated with renal
      developmental malformations. The purpose of this study was to determine whether
      Pax2 protein expression, and that of other proteins important for normal renal
      development, is abnormally distributed in the prenatal kidney of the Brachyrrhine
      (Br) mouse that displays heritable renal hypoplasia. Embryonic 3H1 +/+ and Br/Br
      mice were collected between E11.0 and E18.0. Routine light microscopy and
      immunohistochemical analysis using antibodies to Pax2, E-cadherin, fibronectin,
      laminin, and Type IV collagen were applied to sequential tissue sections. E
      cadherin stained consistently in the renal tubules of both normal and mutant
      animals. Whereas the initial expression of Pax2 corresponded between normal and
      mutant kidneys, it became progressively limited to the nephrogenic zone in +/+
      animals, while distributing erratically in the Br/Br kidney. Fibronectin was not
      expressed in the normal nephrogenic zone but remained abundantly distributed
      throughout the Br/Br kidney. Luminin and Type IV collagen staining revealed a
      deficiency in renal vasculature formation in Br/Br kidneys. Results suggest that
      initial morphological differentiation occurs normally in the Br kidney but that
      subsequent nephric formation is associated with abnormal distribution of Pax2 and
      ECM proteins. (J Histochem Cytochem 49:1081-1097, 2001)

PMID- 11511679
TI  - High-resolution immunocytochemistry of noncollagenous matrix proteins in rat
      mandibles processed with microwave irradiation.
AB  - The mineral phase in calcified tissues represents an additional factor to be
      considered during their preservation for ultrastructural analyses. Microwave (MW)
      irradiation has been shown to facilitate fixative penetration and to improve
      structural preservation and immunolabeling in a variety of soft tissues. The aim
      of the present study was to determine whether MW processing could offer similar
      advantages for hard tissues. Rat hemimandibles were immersed in 4% formaldehyde +
      0.1% glutaraldehyde buffered with 0.1 M sodium cacodylate, pH 7.2, and exposed to
      MWs for three periods of 5 min at temperatures not exceeding 37C. They were then
      decalcified in 4.13% EDTA, pH 7.2, for 15 hr, also under MW irradiation.
      Osmicated and non-osmicated samples were dehydrated in graded concentrations of
      ethanol and embedded in LR White resin. Sections of incisor, molars, and alveolar
      bone were processed for postembedding colloidal gold immunolabeling using
      antibodies against ameloblastin, amelogenin, bone sialoprotein, or osteopontin.
      Ultrastructural preservation of tissues was in most cases comparable to that
      obtained by perfusion-fixation, and there was no difference in distribution of
      labeling with those previously reported for the antibodies used. However, the
      immunoreactivities obtained were generally more intense, particularly at early
      stages of tooth formation. Amelogenin was abundant between differentiating
      ameloblasts and labeling for osteopontin appeared over the Golgi apparatus of
      odontoblasts after initiation of dentine mineralization. We conclude that MW
      irradiation represents a simple method that can accelerate the processing of
      calcified tissues while yielding good structural preservation and antigen
      retention. (J Histochem Cytochem 49:1099-1109, 2001)

PMID- 11511680
TI  - A novel method for simultaneous anterograde and retrograde labeling of spinal
      cord motor tracts in the same animal.
AB  - Examination of repaired spinal cord tracts has usually required separate groups
      of animals for anterograde and retrograde tracing owing to the incompatibility of
      techniques such as tissue fixation. However, anterograde and retrograde labeling
      of different animals subjected to the same repair may not allow accurate
      examination of that repair strategy because widely variable results can occur in
      animals subjected to the same strategy. We have developed a reliable method of
      labeling spinal cord motor tracts bidirectionally in the same animal using DiI, a
      lipophilic dye, to anterogradely label the corticospinal tract and Fluoro-Gold
      (FG) to retrogradely label cortical and brainstem neurons of several spinal cord
      motor tracts in normal and injured adult rats. Other tracer combinations
      (lipophilic dyes or fluorescent dextrans) were also investigated but were less
      effective. We also developed methods to minimize autofluorescence with the DiI/FG
      technique, and found that the DiI/FG technique is compatible with decalcification
      and immunohistochemistry for several markers relevant for studies of spinal cord
      regeneration. Thus, the use of anterograde DiI and retrograde FG is a novel
      technique for bidirectional labeling of the motor tracts of the adult spinal cord
      with fluorescent tracers and should be useful for demonstrating neurite
      regeneration in studies of spinal cord repair.(J Histochem Cytochem 49:1111-1122,
      2001)

PMID- 11511681
TI  - Localization of cytosolic NADP-dependent isocitrate dehydrogenase in the
      peroxisomes of rat liver cells: biochemical and immunocytochemical studies.
AB  - Two types of NADP-dependent isocitrate dehydrogenases (ICDs) have been reported:
      mitochondrial (ICD1) and cytosolic (ICD2). The C-terminal amino acid sequence of
      ICD2 has a tripeptide peroxisome targeting signal 1 sequence (PTS1). After
      differential centrifugation of the postnuclear fraction of rat liver homogenate,
      approximately 75% of ICD activity was found in the cytosolic fraction. To
      elucidate the true localization of ICD2 in rat hepatocytes, we analyzed the
      distribution of ICD activity and immunoreactivity in fractions isolated by
      Nycodenz gradient centrifugation and immunocytochemical localization of ICD2
      antigenic sites in the cells. On Nycodenz gradient centrifugation of the light
      mitochondrial fraction, ICD2 activity was distributed in the fractions in which
      activity of catalase, a peroxisomal marker, was also detected, but a low level of
      activity was also detected in the fractions containing activity for succinate
      cytochrome C reductase (a mitochondrial marker) and acid phosphatase (a lysosomal
      marker). We have purified ICD2 from rat liver homogenate and raised a specific
      antibody to the enzyme. On SDS-PAGE, a single band with a molecular mass of 47 kD
      was observed, and on immunoblotting analysis of rat liver homogenate a single
      signal was detected. Double staining of catalase and ICD2 in rat liver revealed
      co-localization of both enzymes in the same cytoplasmic granules. Immunoelectron
      microscopy revealed gold particles with antigenic sites of ICD2 present mainly in
      peroxisomes. The results clearly indicated that ICD2 is a peroxisomal enzyme in
      rat hepatocytes. ICD2 has been regarded as a cytosolic enzyme, probably because
      the enzyme easily leaks out of peroxisomes during homogenization. (J Histochem
      Cytochem 49:1123-1131, 2001)

PMID- 11511682
TI  - Immunohistochemical localization of taurine in the rat ovary, oviduct, and
      uterus.
AB  - The distribution of the amino acid taurine in the female reproductive organs has
      not been previously analyzed in detail. The aim of this study was to determine
      taurine localization in the rat ovary, oviduct, and uterus by immunohistochemical
      methods. Taurine was localized in the ovarian surface epithelium. The granulosa
      cells and oocytes of primordial follicles were immunonegative. In primary and
      antral follicles, taurine was found mainly in theca cells and oocytes, whereas
      the zona pellucida, antrum, and most granulosa cells were unstained. However,
      taurine immunoreactivity in theca cells and oocytes decreased during follicular
      atresia. During corpora lutea development, the number of immunopositive theca
      lutein cells increased as these cells invaded the granulosa-derived region.
      Therefore, most luteal cells from the mature corpora lutea were stained. In the
      regressing corpora lutea, however, taurine staining in luteal cells decreased. In
      the fimbriae, infundibulum, and uterotubal junction, taurine was localized in
      most epithelial cells. In the ampullar and isthmic segments, taurine was found in
      the cilia of most ciliated cells and in the apical cytoplasm of some non-ciliated
      cells. In the uterus, most epithelial cells were immunopositive during diestrus
      and metestrus, whereas most of them were immunonegative during estrus and
      proestrus. Moreover, taurine immunoreactivity in the oviduct and uterus decreased
      with pregnancy. (J Histochem Cytochem 49:1133-1142, 2001)

PMID- 11511683
TI  - Prolyl 4-hydroxylase isoenzymes I and II have different expression patterns in
      several human tissues.
AB  - Prolyl 4-hydroxylase plays a central role in the synthesis of all collagens. We
      have previously reported that the recently identified Type II isoenzyme is its
      main form in chondrocytes and possibly in capillary endothelial cells, while Type
      I is the main form in many other cell types. We report here that the Type II
      isoenzyme is clearly the main form in capillary endothelial cells and also in
      cultured umbilical vein endothelial cells, whereas no Type I isoenzyme could be
      detected in these cells by immunostaining or Western blotting. The Type II
      isoenzyme was also the main form in cells of the developing glomeruli in the
      fetal kidney and tubular structures of collecting duct caliber in both fetal and
      adult kidney, in occasional sinusoidal structures and epithelia of the bile ducts
      in the liver, and in some cells of the decidual membrane that probably
      represented invasive cytotrophoblasts in the placenta. Osteoblasts in a fetal
      calvaria, i.e., a bone developing by intramembranous ossification, stained
      strongly for both types of isoenzyme. The Type I isoenzyme was the main form in
      undifferentiated interstitial mesenchymal cells of the developing kidney, for
      example, and in fibroblasts and fibroblastic cells in many tissues. Skeletal
      myocytes and smooth muscle cells appeared to have the Type I isoenzyme as their
      only prolyl 4-hydroxylase form. Hepatocytes expressed small amounts of the Type I
      enzyme and very little if any Type II, the Type I expression being increased in
      malignant hepatocytes and cultured hepatoblastoma cells. The data suggest that
      the Type I isoenzyme is expressed especially by cells of mesenchymal origin and
      in developing and malignant tissues, whereas the Type II isoenzyme is expressed,
      in addition to chondrocytes and osteoblasts, by more differentiated cells, such
      as endothelial cells and cells of epithelial structures. (J Histochem Cytochem
      49:1143-1153, 2001)

PMID- 11511684
TI  - Placental alkaline phosphatase expression at the apical and basal plasma membrane
      in term villous trophoblasts.
AB  - Human placental alkaline phosphatase (PLAP) was localized at the apical and basal
      plasma membrane of syncytiotrophoblasts and at the surface of cytotrophoblasts in
      term chorionic villi using immunoelectron microscopy. Similarly, apical and
      basolateral PLAP expression was found in polarized trophoblast-derived BeWo
      cells. Trophoblasts isolated from term placentas exhibited mainly vesicular PLAP
      immunofluorescence staining immediately after isolation. After in vitro
      differentiation into syncytia, PLAP plasma membrane expression was upregulated
      and exceeded that observed in mononuclear trophoblasts. These data call for
      caution in using PLAP as a morphological marker to differentiate
      syncytiotrophoblasts from cytotrophoblasts or as a marker enzyme for placental
      brush-border membranes. (J Histochem Cytochem 49:1155-1164, 2001)

PMID- 11511685
TI  - ADAM-10 protein is present in human articular cartilage primarily in the membrane
      bound form and is upregulated in osteoarthritis and in response to IL-1alpha in
      bovine nasal cartilage.
AB  - The objective of our study was to determine the tissue distribution and
      localization of ADAM-10 protein in human and bovine cartilage and the changes it
      undergoes with cartilage degeneration seen in osteoarthritis (OA) and under the
      influence of interleukin-1 (IL-1). Human normal and OA articular cartilage and
      bovine nasal cartilage cultured in the presence of IL-1alpha were processed for
      histology and immunohistochemistry. ADAM-10 protein was extracted from human
      cartilage and analyzed by Western blotting using anti-ADAM-10 antibodies. Fluor S
      Image analyzer and Quantity One software program were applied to quantify the
      total amount of ADAM-10. ADAM-10 protein was detected in both human and bovine
      cartilage. The strongest immunostaining was found in the cytoplasm and/or cell
      membranes of the superficial and upper middle layer of normal adult human
      cartilage, in the clusters and fibrillated areas of OA cartilage, and in IL
      1alpha-stimulated bovine nasal cartilage. The distribution of ADAM-10 protein in
      bovine nasal cartilage was dependent on the length of exposure to IL-1alpha and
      corresponded to the areas of proteoglycan depletion. By Western blotting analysis
      of human cartilage, ADAM-10 was primarily detected in the membrane-enriched
      fraction and its levels were increased in degenerated and OA cartilage compared
      to normal cartilage. The results of this study suggest that ADAM-10 might be an
      important factor associated with cartilage degenerative processes. (J Histochem
      Cytochem 49:1165-1176, 2001)

PMID- 11511686
TI  - Simultaneous detection of RNA and protein by in situ hybridization and
      immunological staining.
AB  - Proteinase K is widely used in methods for detection of transcripts in biological
      specimens by in situ hybridization (ISH). However, treatment with proteinase K
      hampers detection of RNA and protein simultaneously. We have developed a method
      for double staining of transcripts and proteins by ISH and IHC staining in
      imaginal discs and embryos of Drosophila. Instead of treatment with proteinase K,
      samples are treated with ethanol plus xylene and with acetone. Acetone renders
      cell membranes permeable to probes and antibodies without damaging tissue
      integrity, whereas treatment with proteinase K sometimes damages tissues.
      Treatment of samples with acetone allows hybridization of probe with transcripts
      in tissue. It is also effective for immunological staining of samples after ISH
      with a riboprobe. Thus, our method allows detection not only of transcripts but
      also of specific proteins in relatively intact single samples. (J Histochem
      Cytochem 49:1177-1182, 2001)

PMID- 11511687
TI  - A silver staining method for single-cell gel assay.
AB  - The single-cell gel assay (comet assay) is a very useful microelectrophoretic
      technique for evaluation of DNA damage and repair in individual cells. Usually,
      the comets are visualized and evaluated with fluorescent DNA stains. This
      staining requires specific equipment (e.g., a high-quality fluorescence
      microscope), the slides must be analyzed immediately, and they cannot be stored
      for long periods of time. Here we describe, using human lymphocytes, some
      modifications of the silver staining for comets that significantly increase the
      sensitivity/reproducibility of the assay. This silver staining was compared with
      fluorescence staining and commercial silver stains. (J Histochem Cytochem 49:1183
      1186, 2001)

PMID- 11511688
TI  - Overexpression of NAD(P)H:quinone oxidoreductase 1 in human reproductive system.
AB  - NAD(P)H:quinone oxidoreductase 1 (NQO1; DT-diaphorase; DTD) is a two-electron
      reductase that efficiently bioactivates compounds of the quinone family, such as
      mitomycin C. The observation that DTD is overexpressed in many cancerous tissues
      compared to normal tissues has provided us with a potentially selective target
      that can be exploited in the design of novel anticancer agents. Because of the
      relative lack of information on the cell-specific expression of DTD, the purpose
      of this study was to perform a body mapping of its normal distribution. Tissue
      samples from various components of the human reproductive system were analyzed by
      immunohistochemistry. We found strong expression of this enzyme in testicular
      stromal cells (Leydig cells) and in the epithelium of epididymis, ductuli
      efferentes, and Fallopian tube. These results suggest that DTD-bioactivated
      quinones could be responsible for a selective toxicity on these components of the
      reproductive system and cause clinical problems due to testosterone deficiency
      and infertility. This observation needs to be investigated in preclinical
      evaluation of new anticancer quinones and in patients treated with these
      compounds. (J Histochem Cytochem 49:1187-1188, 2001)

PMID- 11511689
TI  - Stability of nitroblue tetrazolium-based alkaline phosphatase substrates.
AB  - This report demonstrates the stability of NBT substrate after multiple exposures
      to alkaline phosphatase. Perhaps more important than the ability to reuse
      substrates, the report provides some insight into the mechanisms by which
      tetrazoliums are reduced and evidence for the formation of an intermediary
      product, i.e., a half-formazan that is reduced more rapidly. (J Histochem
      Cytochem 49:1189-1190, 2001)

PMID- 11511690
TI  - Mapping of mitochondrial metabolic competence by cytochrome oxidase and succinic
      dehydrogenase cytochemistry.
AB  - To map the mitochondrial capacity to provide adenosine triphosphate (ATP), the
      activities of cytochrome oxidase (COX) and succinic dehydrogenase (SDH) were
      respectively evidenced by diaminobenzidine (DAB) and copper ferrocyanide
      cytochemical techniques in the cerebellar cortex of adult rats. Sampling of the
      positive mitochondria was carried out by the disector procedure. The ratio (R)
      overall area of the precipitates due to COX activity within the single
      mitochondrion/area of the same organelle was automatically calculated to estimate
      enzyme activity vs mitochondrial size. The number of SDH-positive
      mitochondria/microm(3) of tissue (numeric density, Nv) was morphometrically
      calculated. Cytochemistry of key enzymes of the respiratory chain enables
      measurement of the actual capacity of individual mitochondria to provide ATP.
      This quantitative estimation allows morphofunctional mapping of the mitochondrial
      metabolic competence in discrete tissue and/or cellular compartments. (J
      Histochem Cytochem 49:1191-1192, 2001)

PMID- 11511691
TI  - Immunohistochemical analyses of cell cycle-related proteins, apoptosis, and
      proliferation in pituitary adenomas.
AB  - To analyze the cell cycle regulatory mechanisms in the growth of pituitary
      adenomas, we investigated immunohistochemically the expression of the cell cycle
      related proteins cyclin A and p27 in 48 pituitary adenomas. The frequency of
      apoptosis and the proliferative potential were also examined. The percentage of
      apoptotic cells was evaluated by immunohistochemical analysis using the anti
      single-strand DNA antibody. The proliferative potential was assessed using the
      anti-Ki-67 antibody. The mean cyclin A labeling index (LI) for the non-recurrent
      group was 1.03% and for the recurrent group 2.31%. A positive linear correlation
      between cyclin A LI and Ki-67 LI was found. The mean p27 LI for the non-recurrent
      group was 67.4% and for the recurrent group 47.0%. There were significant
      differences in cyclin A LI and p27 LI between the non-recurrent group and the
      recurrent group. The mean apoptotic rate for the non-recurrent group was 0.87%
      and for the recurrent group 1.05%. There was no significant difference.
      Multivariate regression analysis revealed that high cyclin A LI and high Ki-67 LI
      were significant factors for shorter progression-free survival. The results
      suggest that the cyclin A LI is a useful prognostic factor in pituitary adenomas.
      (J Histochem Cytochem 49:1193-1194, 2001)

PMID- 11511692
TI  - Cellular distribution of GAP-43 mRNA in hippocampus and cerebellum of adult rat
      brain by in situ RT-PCR.
AB  - The growth-associated protein GAP-43 is a presynaptic membrane phosphoprotein
      that plays a key role in guiding the growth of axons and in modulating the
      formation of new synapses. To identify the cells that synthesize GAP-43 mRNA, we
      applied direct in situ reverse transcription-polymerase chain reaction (in situ
      RT-PCR) in cerebellum and hippocampus of adult rat brain. In situ RT-PCR revealed
      GAP-43 mRNA in cerebellar granule cells, in Purkinje cells and in some
      interneurons of the molecular layer. Previous in situ hybridization studies had
      demonstrated a dense label throughout the granular layer of the cerebellar cortex
      but no labeling of other cerebellar neurons. Hippocampal cells showing distinct
      GAP-43 mRNA signal after in situ RT-PCR were CA1 and CA3 pyramidal neurons, CA4
      hilar cells, and dentate gyrus granule cells, whereas in situ hybridization
      studies had detected GAP-43 mRNA only in CA3 and CA1 pyramidal neurons. Our data
      indicate that GAP-43 mRNA is widely distributed, suggesting that many cell types
      are potentially involved in synaptic plasticity events. (J Histochem Cytochem
      49:1195-1196, 2001)

PMID- 11511693
TI  - HPV for cervical cancer screening: is the era of the molecular pap smear upon us?
AB  - Based on the best estimates of the prevalence of human Papillomavirus infection
      in the United States, the overall HPV prevalence in the target population is
      approximately 20%. The prevalence varies greatly with age, being as high as
      approximately 50% in the third decade to less than 5% in the sixth. These data
      have implications for a discussion about the utility of human Papillomavirus
      testing as a screening procedure.(J Histochem Cytochem 49:1197-1198, 2001)

PMID- 11511694
TI  - The pyramidal cell in cognition: a comparative study in human and monkey.
AB  - Here we present evidence that the pyramidal cell phenotype varies markedly in the
      cortex of different anthropoid species. Regional and species differences in the
      size of, number of bifurcations in, and spine density of the basal dendritic
      arbors cannot be explained by brain size. Instead, pyramidal cell morphology
      appears to accord with the specialized cortical function these cells perform.
      Cells in the prefrontal cortex of humans are more branched and more spinous than
      those in the temporal and occipital lobes. Moreover, cells in the prefrontal
      cortex of humans are more branched and more spinous than those in the prefrontal
      cortex of macaque and marmoset monkeys. These results suggest that highly
      spinous, compartmentalized, pyramidal cells (and the circuits they form) are
      required to perform complex cortical functions such as comprehension, perception,
      and planning.

PMID- 11511695
TI  - Different signaling pathways mediate regenerative versus developmental sensory
      axon growth.
AB  - Recent advances in defining neurotrophin signaling mediators have provided
      insights into the signal transduction mechanisms that underlie axon growth.
      Evidence is accumulating that major Trk effectors regulate the morphological
      development of embryonic peripheral neurons. Less is known about signaling
      related to the robust axon extension that follows peripheral axotomy of adult
      neurons. Regenerative axon growth can be mimicked in vitro by a "conditioning"
      lesion performed 2 weeks before culture (Smith and Skene, 1997). Previous work
      has implicated both neurotrophins and cytokines in this response. Because signal
      transduction mediators of both of these families of growth factors are well
      characterized, we have compared the role of neurotrophin and cytokine signaling
      in developmental versus regenerative sensory axon growth. Chemical inhibitors
      were administrated to embryonic and axotomized sensory neurons in vitro to block
      the activation of Erk kinase (MEK)-extracellular signal-regulated kinase (ERK),
      phosphatidylinositol-3 kinase (PI3-K), and janus kinase (JAK) signaling. As
      expected, both MEK and PI3-K inhibition blocked axon growth from both naive and
      NGF-stimulated embryonic day 13 sensory neurons, whereas inhibition of JAK
      phosphorylation had no effect. In contrast, neither MEK nor PI3-K inhibitors
      blocked elongation of adult sensory neurons after a conditioning lesion. However,
      the addition of a JAK2 inhibitor prevented the regenerative axon response.
      Consistent with these pharmacological results, the percentage of neurons showing
      intense nuclear signal transducers and activators of transcription 3
      phosphorylation after a conditioning lesion was markedly increased compared with
      controls. These observations demonstrate that the signaling mediators that
      underlie regenerative axon growth are distinct from those used during development
      and suggest that cytokine signaling may be critical to peripheral nervous system
      regeneration.

PMID- 11511696
TI  - Role of the vestibular system in the pathophysiology of spasmodic torticollis.

PMID- 11511697
TI  - What is the most sensitive non-invasive strategy for the diagnosis of
      intracranial aneurysms?

PMID- 11511698
TI  - Divining dementia.

PMID- 11511699
TI  - Reflex sympathetic dystrophy.

PMID- 11511700
TI  - Preclinical syndromes predict dementia: the Sydney older persons study.
AB  - OBJECTIVES: To identify if preclinical syndromes for Alzheimer's disease,
      vascular dementia, and Parkinson's disease and related dementias exist.
      Identification of dementia at early or even preclinical stages has important
      implications for treatment. METHODS: A community dwelling sample of 647 subjects
      aged 75 and over at recruitment were followed up for a mean period of 3.19 years
      (range 2.61 to 4.51 years). Each subject was asked to participate in a medical
      assessment which included a standardised medical history examining both past and
      current health and medication usage; a neuropsychological battery (mini mental
      state examination, Reid memory test, verbal fluency, subsets of the Boston naming
      test and similarities, clock drawing and copied drawings) and physical
      examination. Preclinical syndromes for the three predominant dementias
      (Alzheimer's disease, vascular dementia and Parkinson's disease, and related
      dementias) and their combinations were defined using cognitive, motor, and
      vascular features. Their longitudinal outcome as defined by death and dementia
      incidence was examined. RESULTS: Preclinical syndromes affected 55.7% (n=299) of
      subjects. Preclinical syndromes showed a trend for an increased odds of death
      (odds ratio 1.72, p=0.056) and a significantly increased odds of developing
      dementia (odds ratio 4.81, p<0.001). Preclinical syndromes were highly sensitive,
      detecting 52 of 58 (89.7%) incident dementias. Two hundred and sixteen of 268
      (80.6%) preclinical subjects did not show dementia over the 3 year period
      (positive predictive value 19.4%). Subjects defined as having a combination of
      cognitive, extrapyramidal, and vascular features were at greatest risk of
      progressing to dementia. CONCLUSIONS: Preclinical syndromes were sensitive and
      significant predictors of dementia. In view of their poor positive predictive
      value, the preclinical syndromes as defined in this study remain a research tool
      needing both definitional refinement and greater periods of observation. Multiple
      coexistent preclinical disorders resulted in a greater incidence of dementia,
      providing evidence for an additive role between multiple disorders.

PMID- 11511701
TI  - Occupation during life and risk of dementia in French elderly community
      residents.
AB  - OBJECTIVE: To determine whether principal occupation during life is a risk factor
      for incident Alzheimer's disease, vascular dementia, or dementia with
      parkinsonism. METHODS: This study was carried out from the PAQUID (Personnes
      Agees QUID) cohort, an epidemiological study on normal and pathological aging
      after 65 years in the south west of France. At baseline, 2950 non-demented people
      living at home were identified and re-examined 1, 3, 5, 8, and 10 years later
      with identical standardised neurological and neuropsychological measures. Cox
      proportional hazards models with delayed entry were used, taking age as the time
      scale and adjusting for sex, education, tobacco, and wine consumption to estimate
      the risk ratio (RR) of incident dementia, Alzheimer's disease, vascular dementia,
      and dementia with parkinsonism associated with occupational category. RESULTS: Of
      the 2950 subjects, 393 became demented, of whom 251 had Alzheimer's disease, 112
      had vascular dementia, and 27 had dementia with parkinsonism. The risk of
      Alzheimer's disease was not related to a given occupation. However the risk of
      dementia with parkinsonism seemed to be increased in farmers in comparison with
      professionals and managerials, particularly among women (RR 7.47; 95%CI, 1.80
      31.07). CONCLUSION: The data suggest that occupation does not change the risk of
      Alzheimer's disease, which seems to be more influenced by cognitive abilities in
      childhood and adolescence than by occupation in adult life. However, being a
      farmer may increase the risk of dementia with parkinsonism among women;
      occupation could act by the way of differences in health behaviour or in exposure
      to environmental factors.

PMID- 11511702
TI  - Neuropsychiatric aspects of Huntington's disease.
AB  - OBJECTIVE: Neuropsychiatric symptoms are common in Huntington's disease and have
      been considered its presenting manifestation. Research characterising these
      symptoms in Huntington's disease is variable, however, encumbered by limitations
      within and across studies. Gaining a better understanding of neuropsychiatric
      symptoms is essential, as these symptoms have implications for disease
      management, prognosis, and quality of life for patients and caregivers. METHOD:
      Fifty two patients with Huntington's disease were administered standardised
      measures of cognition, psychiatric symptoms, and motor abnormalities. Patient
      caregivers were administered the neuropsychiatric inventory. RESULTS: Ninety
      eight per cent of the patients exhibited neuropsychiatric symptoms, the most
      prevalent being dysphoria, agitation, irritability, apathy, and anxiety. Symptoms
      ranged from mild to severe and were unrelated to dementia and chorea.
      CONCLUSIONS: Neuropsychiatric symptoms are prevalent in Huntington's disease and
      are relatively independent of cognitive and motor aspects of the disease.
      Hypothesised links between neuropsychiatric symptoms of Huntington's disease and
      frontal-striatal circuitry were explored. Findings indicate that dimensional
      measures of neuropsychiatric symptoms are essential to capture the full range of
      pathology in Huntington's disease and are vital to include in a comprehensive
      assessment of the disease.

PMID- 11511704
TI  - What is the most sensitive non-invasive imaging strategy for the diagnosis of
      intracranial aneurysms?
AB  - OBJECTIVES: To determine whether combining non-invasive tests for intracranial
      aneurysms together would significantly improve aneurysm detection over individual
      tests. METHODS: 114 patients undergoing intra-arterial digital subtraction
      angiography to confirm or exclude an intracranial aneurysm were also examined by
      CT angiography, MR angiography, and transcranial power Doppler ultrasound. The
      reviewers and ultrasonographers were blinded to the angiogram result, other
      imaging results and all clinical information. RESULTS: The combination of non
      invasive tests did improve diagnostic performance on a per patient basis. The
      combination of power Doppler and CT angiography had the greatest sensitivity for
      aneurysm detection (0.83; 05% confidence interval (95% CI) 0.66-0.93) and the
      level of agreement for this strategy with the reference angiographic standard was
      excellent (kappa 0.84; 95% CI 0.72-0.95). The improvement in sensitivity of
      adding power Doppler to CT angiography was not significant (p=0.55) but the
      improvement in the level of agreement with the reference standard was
      substantial. However, even the most sensitive combination strategy performed
      poorly in the detection of small (3-5 mm) and very small (<3 mm) aneurysms with a
      sensitivity of 0.43 (95% CI 0.23-0.66) and 0.00 (95% CI 0.00-0.31) respectively.
      CONCLUSIONS: The addition of transcranial power Doppler ultrasound to either CT
      angiography or MR angiography does improve diagnostic performance on a per
      patient basis but aneurysms of 5 mm or smaller can still not be reliably
      identified by current standard clinical non-invasive imaging modalities.

PMID- 11511703
TI  - Relations between hypometabolism in the posterior association neocortex and
      hippocampal atrophy in Alzheimer's disease: a PET/MRI correlative study.
AB  - OBJECTIVES: Hippocampal atrophy and hypometabolism in the posterior association
      neocortex are two well known features of Alzheimer's disease. A correlation
      between these two features was reported twice previously, suggesting intriguing
      relations. This question has been reassessed, this time controlling for severity
      of dementia as well as assessing each side of the brain separately and using a
      voxel based image analysis in addition to the previously employed regions of
      interest (ROIs). PATIENTS AND METHODS: Eleven patients were studied with probable
      Alzheimer's disease and mild to moderate dementia in whom both volume MRI and PET
      assessed cerebral glucose consumption (CMRGlc) were available. Hypothesis driven
      correlations between hippocampal width (an index of atrophy) and CMRGlc were
      performed for two posterior association regions, the superior temporal and the
      inferior parietal (angular gyrus) cortices, using ROIs set separately for each
      hemisphere. To confirm significant correlations from the ROIs approach, if any,
      and to assess their specificity for the posterior association neocortex, CMRGlc
      image voxel based analysis of correlations with hippocampal width was then
      carried out. RESULTS: There was a significant correlation, in the positive
      neurobiologically expected-direction, between right hippocampal width and right
      angular gyrus metabolism (p< 0.01, Spearman), which remained significant with
      Kendall partial correlation controlling for dementia severity (estimated by mini
      mental state scores). Statistical non-parametric mapping (SnPM) confirmed this
      correlation (p< 0.025), and showed a single additional correlation in the right
      middle temporal gyrus (p< 0.005), which is also part of the posterior association
      cortex. CONCLUSION: The findings with both ROIs and voxel based mapping replicate
      earlier reports of a relation between hippocampal atrophy and ipsilateral
      association cortex hypometabolism in Alzheimer's disease, and for the first time
      document that this relation is both region specific and independent of the
      dementing process itself. Why the correlation was significant only for the right
      hemisphere is unclear but may be related to the limited sample. Hippocampal
      neocortical disconnection due to early and severe medial temporal lobe pathology
      may at least partly explain the posterior association cortex hypometabolism found
      in Alzheimer's disease.

PMID- 11511705
TI  - Serum concentration of adhesion molecules in patients with delayed ischaemic
      neurological deficit after aneurysmal subarachnoid haemorrhage: the
      immunoglobulin and selectin superfamilies.
AB  - OBJECTIVES: Adhesion molecules are involved in the pathogenesis of cerebral
      ischaemia and may play a part in the pathophysiology of delayed ischaemic
      neurological deficit (DIND) after aneurysmal subarachnoid haemorrhage. It was
      hypothesised that after aneurysmal subarachnoid haemorrhage, adhesion molecules
      may play a part in the pathophysiology of DIND as reflected by significantly
      altered serum concentrations in patients with and without DIND. METHODS: In a
      prospective study, mean serum concentrations of ICAM-1, VCAM-1, PECAM, and E, P,
      and L-selectin were compared between patients without (n=23) and with (n=13) DIND
      in patients with World Federation of Neurological Surgeons (WFNS) grades 1 or 2
      subarachnoid haemorrhage. Serum was sampled from patients within 2 days of
      haemorrhage and on alternate days until discharge. Concentrations of adhesion
      molecules were measured by standard procedures using commercially available
      enzyme linked immunoabsorbent assays. RESULTS: There were non-significant
      differences in serum concentrations of ICAM-1 (290.8 ng/ml v 238.4 ng/ml,
      p=0.0525), VCAM-1 (553.2 ng/ml v 425.8 ng/ml, p=0.053), and PECAM (22.0 ng/ml v
      21.0 ng/ml, p=0.56) between patients without and with DIND respectively. The E
      selectin concentration between the two patient groups (44.0 ng/ml v 37.4 ng/ml,
      p=0.33) was similar. The P-selectin concentration, however, was significantly
      higher in patients with DIND compared with those patients without DIND (149.5
      ng/ml v 112.9 ng/ml, p=0.039). By contrast, serum L-selectin concentrations were
      significantly lower in patients with DIND (633.8 ng/ml v 897.9 ng/ml, p=0.013).
      CONCLUSIONS: Of all the adhesion molecules examined in this study, P and L
      selectin are involved in the pathophysiology of DIND after aneurysmal
      subarachnoid haemorrhage.

PMID- 11511707
TI  - Selective sparing of face learning in a global amnesic patient.
AB  - OBJECTIVE: To test the hypothesis that visual memory for faces can be dissociated
      from visual memory for topographical material. METHOD: A patient who developed a
      global amnesic syndrome after acute carbon monoxide poisoning is described. A
      neuroradiological examination documented severe bilateral atrophy of the
      hippocampi. RESULTS: Despite a severe anterograde memory disorder involving
      verbal information, abstract figures, concrete objects, topographical scenes, and
      spatial information, the patient was still able to learn previously unknown human
      faces at a normal (and, in some cases, at a higher) rate. CONCLUSIONS: Together
      with previous neuropsychological evidence documenting selective sparing of
      topographical learning in otherwise amnesic patients, this case is indicative of
      the fact that the neural circuits involved in face recognition are distinct from
      those involved in the recognition of other visuoperceptual material (for example,
      topographical scenes).

PMID- 11511706
TI  - Cerebral metabolic impairment in patients with obstructive sleep apnoea: an
      independent association of obstructive sleep apnoea with white matter change.
AB  - OBJECTIVES: To determine the relation between severity of obstructive sleep
      apnoea (OSA) and degree of cerebral metabolic impairment. METHODS: Fifty five
      patients with habitual snoring and excessive daytime sleepiness underwent
      standard overnight polysomnography and magnetic resonance spectroscopy
      separately. Proton MR spectra were measured with two dimensional chemical shift
      imaging (repetition time; 1500 ms, echo time; 135 ms). Severity of cerebral
      metabolic impairment was assessed by the N-acetylaspartate (NAA)/choline ratios
      for the cerebral cortex and white matter. Severity of OSA was assessed by the
      apnoea-hypopnoea index (AHI) and the minimum value of peripheral oxyhaemoglobin
      saturation. All patients were evaluated for the presence or absence of
      comobidities including hypertension, cardiac disease, diabetes mellitus, and
      hyperlipidaemia. Univariate analysis of variance (ANOVA) and mulitple linear
      regression analysis were used for statistical analyses. RESULTS: Univariate ANOVA
      disclosed significant effects of AHI, age, and the presence or absence of
      hypertension on the NAA/choline ratio for cerebral white matter (p=0.011,
      p=0.028, p=0.0496, respectively). The AHI had a significant negative association
      with the NAA/choline ratio for cerebral white matter, independent of age and the
      presence or absence of cardiac disease, in the final multivariate regression
      model (standardised partial regression coefficient=-0.417, p<0.001). No
      significant relation was found between severity of OSA and the NAA/choline ratio
      for the cerebral cortex. Age alone had a significant effect on the NAA/choline
      ratio for the cerebral cortex on univariate ANOVA (p<0.001) and a significant
      negative association with the NAA/choline ratio for the cerebral cortex in the
      regression model (r=-0.552, p<0.001). CONCLUSIONS: A significant relation exists
      between AHI and the degree of metabolic impairment in cerebral white matter in
      patients with OSA.

PMID- 11511709
TI  - Ammon's horn and the hippocampus.

PMID- 11511708
TI  - A new nephelometric assay for beta-trace protein (prostaglandin D synthase) as an
      indicator of liquorrhoea.
AB  - OBJECTIVES: To determine the sensitivity and specificity of a nephelometric beta
      trace protein assay for the diagnosis of liquorrhoea. METHODS: One hundred and
      forty clinical samples with suspected liquorrhoea were analysed by a newly
      developed nephelometric assay. An established electroimmunoassay served as a
      reference method. The sensitivity and specificity of the beta-trace nephelometric
      assay were calculated by a 2x2 contingency table for 10 different versions of a
      dichotomised nephelometric variable. In 52 patients (79 samples), the
      nephelometric findings were validated by referring to the clinical diagnosis
      based on the course of the disease, imaging techniques, and surgical inspection.
      RESULTS: Given a specificity of 100%, a beta-trace protein concentration of 6
      mg/l or higher in a sample indicated liquorrhoea with a sensitivity of 92%
      compared with the reference method and of 93% compared with the clinical
      evaluation. The relation between the electroimmunoassay and the nephelometric
      assay was highly significant (p<0.001). CONCLUSIONS: The nephelometric beta-trace
      protein assay is a simple and rapid method for the detection of liquorrhoea with
      high sensitivity and specificity and may facilitate the diagnosis of fistulas
      leaking CSF.

PMID- 11511710
TI  - Epidemiology of seropositive myasthenia gravis in Greece.
AB  - OBJECTIVES: To study the epidemiological characteristics of myasthenia gravis in
      Greece. METHODS: A population based study was carried out of seropositive
      myasthenia gravis in Greece for the period from 1 January 1983 to 30 June 1997;
      843 patients were studied. RESULTS: The average annual incidence for the period
      1992-7, for which the database is complete, was 7.40/million population/year
      (women 7.14; men 7.66). On 1 July 1997, there were 740 prevalent cases. The point
      prevalence rate was 70.63/million (women 81.58; men 59.39). The average overall
      annual mortality rate in the patients was 0.67/million population (women 0.53;
      men 0.82), and the mortality rate attributed to myasthenia gravis was
      0.43/million population (women 0.41; men 0.45). The average age at onset was
      46.50 years (women 40.16; men 54.46), and the mean age of the prevalent patients
      was 52.58 (women 47.65; men 59.48). The women:men incidence ratio was 1:1.04, and
      the prevalence ratio was 1.41:1. It is predicted that the prevalence and women:
      men prevalence ratio would increase if the patient list included all patients
      with a date of onset before 1983. CONCLUSIONS: The largest epidemiological study
      ever performed on myasthenia gravis is presented. The most important
      epidemiological indexes are provided.

PMID- 11511711
TI  - Postgastrectomy polyneuropathy with thiamine deficiency.
AB  - OBJECTIVE: Polyneuropathy has been reported after gastrectomy performed to treat
      various lesions. Although thiamine deficiency is a possible cause of this
      neuropathy, the pathogenesis still remains to be clarified. Seventeen patients
      with peripheral neuropathy with thiamine deficiency after gastrectomy are
      described. METHODS: Seventeen patients with polyneuropathy after gastrectomy
      accompanied by thiamine deficiency were selected. Patients were restricted to
      those with total or subtotal gastric resection to treat ulcer or neoplasm.
      Patients who had undergone operations to treat morbid obesity were excluded.
      RESULTS: Intervals between the operation and onset of neuropathy varied from 2
      months to 39 years. Most patients did not seem malnourished. Serum concentrations
      of B vitamins other than thiamine were nearly normal. Symmetric motor-sensory
      polyneuropathy, predominantly involving the lower limbs, had progressed over
      intervals varying from 3 days to 8 years. Relative degrees of motor and sensory
      impairment also varied extensively. Some cases that progressed rapidly mimicked
      Guillain-Barre syndrome. Electrophysiological and pathological findings were
      those of axonal neuropathy. Substantial functional recovery from polyneuropathy
      was seen in most patients by 3 to 6 months after initiating thiamine
      supplementation. Motor recovery was better than sensory recovery. CONCLUSIONS:
      Various symptoms were seen in patients with postgastrectomy neuropathy. Thiamine
      deficiency should be considered in the differential diagnosis of motor-sensory
      polyneuropathy after gastrectomy.

PMID- 11511712
TI  - The SF-36 in multiple sclerosis: why basic assumptions must be tested.
AB  - OBJECTIVES: To evaluate, in people with multiple sclerosis, two psychometric
      assumptions that must be satisfied for valid use of the medical outcomes study 36
      item short form health survey (SF-36): the data are of high quality and, it is
      legitimate to generate scores for eight scales and two summary measures using the
      standard algorithms. METHODS: SF-36 data from 438 people representing the full
      range of multiple sclerosis were examined (mean age 48; 70% women). Data quality
      (per cent missing data and computable scale and summary scores) were determined,
      six scaling criteria were tested to determine the legitimacy of generating the
      eight SF-36 scale scores using Likert's method of summed ratings, and two scaling
      criteria were tested to determine the appropriateness of the standard SF-36
      algorithms for weighting scale scores to generate two summary measures. RESULTS:
      Data quality was excellent except in the most disabled subgroup where missing
      responses reached a maximum of 16.5% and summary scores could only be computed
      for 72%. There was clear support for the generation of SF-36 scale scores. Item
      response distributions were symmetric, item mean scores and variances were
      equivalent, corrected item-total correlations were high (range 0.46-0.85) and
      similar, and definite scaling success rates exceeded 96%. Nevertheless, there
      were notable floor or ceiling effects in four of the eight scales. Assumptions
      for generating two SF-36 summary measures were only partially satisfied. Although
      principal components analysis suggested a two component model, these components
      explained less than 60% of the total variance in SF-36 scales, and less than 75%
      of the variance in five of the eight scales. Moreover, scale to component
      correlations did not support the use of scale weights derived from United States
      population data. CONCLUSIONS: When using the SF-36 as a health measure in
      multiple sclerosis summary scores should be reported with caution.

PMID- 11511713
TI  - Treatment of erectile dysfunction with sildenafil citrate (Viagra) in
      parkinsonism due to Parkinson's disease or multiple system atrophy with
      observations on orthostatic hypotension.
AB  - OBJECTIVES: To assess the efficacy and safety of sildenafil citrate (Viagra) in
      men with erectile dysfunction and parkinsonism due either to Parkinson's disease
      or multiple system atrophy. METHODS: Twenty four patients with erectile disease
      were recruited, 12 with Parkinson's disease and 12 with multiple system atrophy,
      into a randomised, double blind, placebo controlled, crossover study of
      sildenafil citrate. The starting dose was 50 mg active or placebo medication with
      the opportunity for dose adjustment depending on efficacy and tolerability. The
      international index of erectile function questionnaire (IIEF) was used to assess
      treatment efficacy and a quality of life questionnaire to assess the effect of
      treatment on sex life and whole life. Criteria for entry included a definite
      neurological diagnosis and a standing systolic blood pressure of 90-180 mm Hg and
      diastolic blood pressure of 50-110 mm Hg, on treatment if necessary. Blood
      pressure was taken at randomisation (visit 2) and crossover (visit 5) lying,
      sitting, and standing, before and 1 hour after taking the study medication in
      hospital. RESULTS: Sidenafil citrate was efficacious in men with parkinsonism
      with a significant improvement, as demonstrated in questionnaire responses, in
      ability to achieve and maintain an erection and improvement in quality of sex
      life. In Parkinson's disease there was minimal change in blood pressure between
      active and placebo medication. In multiple system atrophy, six patients were
      studied before recruitment was stopped because three men showed a severe drop in
      blood pressure 1 hour after taking the active medication. Two were already known
      to have orthostatic hypotension and were receiving treatment with ephedrine and
      midodrine but the third had asymptomatic hypotension. However, the blood
      pressures in all three had been within the inclusion criterion for the study
      protocol. Despite a significant postural fall in blood pressure after sildenafil,
      all patients with multiple system atrophy reported a good erectile response and
      were reluctant to discontinue the medication. CONCLUSIONS: Sidenafil citrate (50
      mg) is efficacious in the treatment of erectile dysfunction in parkinsonism due
      to Parkinson's disease or multiple system atrophy; however, it may unmask or
      exacerbate hypotension in multiple system atrophy. As Parkinson's disease may be
      diagnostically difficult to distinguish from multiple system atrophy, especially
      in the early stages, we recommend measurement of lying and standing blood
      pressure before prescribing sildenafil to men with parkinsonism. Furthermore,
      such patients should be made aware of seeking medical advice if they develop
      symptoms on treatment suggestive of orthostatic hypotension.

PMID- 11511715
TI  - Clinical comparison of the Spiegelberg parenchymal transducer and ventricular
      fluid pressure.
AB  - The Spiegelberg brain pressure catheter is a low cost implantable intracranial
      pressure measuring system which has the unique ability to perform regular
      automatic zeroing. A new version of the catheter has become available with a
      subdural bolt fixation to allow insertion of the device into the brain
      parenchyma. The accuracy of this system has been evaluated in comparison with a
      ventricular fluid pressure method in a series of patients to determine its
      accuracy and utility in the clinical environment. Hourly readings from the
      Spiegelberg system have been compared with those obtained using a standard
      pressure transducer connected to an external ventricular drain. Measurements
      continued while there was a clinical need for CSF drainage. Eleven patients were
      recruited to the study and data were recorded for periods ranging from 40 to 111
      hours. A good agreement between the two systems was obtained. In 10 cases the
      mean difference was less than +/-1.5 mm Hg and the dynamic changes in value were
      contemporaneous. In one case an intracerebral haemorrhage developed around the
      tips of the Spiegelberg catheter and significant differences occurred between the
      two methods of measurement. In conclusion, the Spiegelberg parenchymal transducer
      provides an accurate measurement of intracranial pressure when compared with
      ventricular pressure. The transducer was found to be robust in the clinical
      environment and very popular with the nursing staff. Further studies may
      determine whether the complication rate of this system is comparable with other
      available devices.

PMID- 11511714
TI  - Outcome of unilateral pallidotomy in advanced Parkinson's disease: cohort study
      of 32 patients.
AB  - OBJECTIVES: In a randomised trial to study the efficacy of unilateral pallidotomy
      in patients with advanced Parkinson's disease, patients having pallidotomy within
      1 month after randomisation were compared with patients having pallidotomy 6
      months after the primary outcome assessment. Of the 37 patients enrolled 32 had a
      unilateral pallidotomy. The follow up study of these patients is presented to
      report (1) clinical outcome; (2) adverse effects; (3) cognitive and behavioural
      effects; (4) relation between lesion location and outcome; and (5) preoperative
      patient characteristics predictive for good outcome. METHODS: Outcome measures
      were the motor section of the unified Parkinson's disease rating scale (UPDRS),
      levodopa induced dyskinesias, disability, quality of life, and a comprehensive
      neuropsychological assessment. Multivariate logistic regression was used to
      identify preoperative patient characteristics independently associated with good
      outcome. RESULTS: Off phase assessment showed a reduction in parkinsonism from 49
      to 36.5 points on the UPDRS 6 months after surgery. Improvements were also
      demonstrated for activities of daily living and quality of life. In the on phase
      dyskinesias were reduced. All effects lasted up to 12 months after surgery. Three
      patients had major permanent adverse effects. Besides worsening of verbal fluency
      after left sided surgery, systematic cognitive deterioration was not detected.
      Patients taking less than 1000 levodopa equivalent units (LEU)/day were more
      likely to improve. CONCLUSIONS: The positive effects of unilateral pallidotomy
      are stable up to 1 year after surgery. Patients taking less than 1000 LEU per day
      were most likely to improve.

PMID- 11511716
TI  - Absence of nystagmus during REM sleep in patients with vestibular neuritis.
AB  - Saccades, including fast phases of nystagmus, disappear during drowsiness and non
      rapid eye movement (NREM) sleep, but are present during the alert state and REM
      sleep. The purpose of this study was to determine whether spontaneous nystagmus
      is present in patients with vestibular neuritis during REM sleep. Eight patients
      with spontaneous nystagmus due to vestibular neuritis and eight control patients
      without any nystagmus underwent at least one night of polysomnography. Fast
      phases of nystagmus were analyzed. The number of right and left horizontal
      saccades were counted, first during 3-5 minute samples of the awake state before
      sleep onset, then during the first REM episode and the last REM episode of
      nocturnal sleep, and finally during the alert state in the morning after
      nocturnal sleep. All patients with vestibular neuritis showed significantly more
      saccades (fast phases) towards the side contralateral to their vestibular lesion
      in the awake state before and after the polysomnography. This reflects their
      spontaneous nystagmus. By contrast, during REM sleep the patients with vestibular
      neuritis showed no preponderance in saccade direction. The eye movement pattern
      in REM was the same for patients and controls. In conclusion, peripheral
      vestibular imbalance producing nystagmus in vestibular neuritis in the awake
      state is not active at the brain stem level during REM sleep.

PMID- 11511717
TI  - Symptomatic unruptured capillary telangiectasia of the brain stem: report of
      three cases and review of the literature.
AB  - Three young patients with transient or intermittent focal neurological signs
      suggesting brain stem involvement are described, in whom high field MRI showed
      focal areas of hyperintensity in T2 weighted spin echo images, hypointensity in
      T2* weighted gradient echo images, and enhancement in postcontrast T1 weighted
      images consistent with unruptured capillary telangiectasia of the brain stem. The
      first patient was a 28 year old woman who complained of recurrent left ear
      tinnitus, exacerbated during the menstrual period; MRI demonstrated that the
      vascular anomaly involved the left acoustic pathway. The second patient was a 30
      year old woman who had three episodes of paroxysmal left lip movement 4 weeks
      after child delivery; MRI showed capillary telangiectasia in the right
      corticonuclear pathway. The third patient, a 36 year old man, had a transient
      right Bell's palsy; MRI disclosed two circumscribed areas consistent with
      capillary telangiectasia in the left corticospinal tract and medial longitudinal
      fasciculus. Steroid receptors in the telangiectatic vessels walls might account
      for the recurrent and transient course seen in our two female patients. Awareness
      of the MRI features of capillary telangiectasia may help in defining the real
      incidence, clinical correlation, and the risk of haemorrhagic complications of
      these vascular malformations.

PMID- 11511718
TI  - Relation between electroconvulsive therapy, cognitive side effects, neuron
      specific enolase, and protein S-100.
AB  - OBJECTIVE: To investigate whether electroconvulsive therapy (ECT) induces brain
      tissue damage expressed as an increase in neuron specific enolase and protein S
      100. METHODS: A total of 179 serial measurements of S-100 and NSE serum
      concentrations were performed on 14 patients during the course of a bilaterally
      stimulated ECT series. Cognitive performance was assessed by psychometric testing
      carried out on the day before the start of ECT as well as on the days after the
      third, sixth, and last ECT. Pre-ECT and post-ECT concentrations of NSE and S-100
      were compared by non-parametric tests. RESULTS: On average, 9.5 (SD 2.9) (range 3
      12) ECTs were applied; 13 of 14 patients received at least six ECTs. The average
      duration of convulsion (computed for all ECTs) was 29.0 (SD 10.5) seconds. At no
      point during the ECT series was there a significant increase in the average NSE
      or S-100 concentrations compared with the baseline investigation before the start
      of the ECT series. The maximal measured post-ECT values of NSE and S-100 were
      26.6 ng/ml and 0.46 ng/ml, respectively. The cumulative energy doses applied,
      seizure durations, and ECT induced changes in cognitive performance scores were
      never significantly correlated with the NSE or S-100 serum concentrations.
      CONCLUSION: This pattern of findings suggests that a modern ECT, fulfilling
      current quality standards, induces no brain tissue damage detectable by changes
      in NSE or protein S-100.

PMID- 11511719
TI  - JC virus regulatory region rearrangements in the brain of a long surviving
      patient with progressive multifocal leukoencephalopathy.
AB  - JC virus (JCV) infection of oligodendrocytes causes demyelination in brains of
      patients with with progressive multifocal leukoencephalopathy (PML). Expansion of
      demyelination throughout the brain is not fully understood. The opportunity was
      taken to investigate the postmortem brain of a long surviving patient with PML
      for whom diagnosis was made 4 years before death based on pathological and
      virological findings of a brain biopsy. Four distinct regulatory sequences in the
      JCV genome were detected (designated as JW-1 to 4) from various regions of the
      necropsied brain. All regulatory sequences were rearranged forms that could be
      produced from the archetype by deletions and duplications. JW-1 and 2 shared some
      structural features not present in JW-3 and 4 and vice versa. JW-1 was
      distributed throughout the brain, whereas JW-2, 3, and 4 were restricted to only
      part of the brain. JW-1 and 2 had been detected in the initial brain biopsy 4
      years earlier. These findings suggested that brain lesions in advanced stages
      were generated not only by expansion of the original variant (JW-1) of JCV but
      also by delayed growth of two other variants (JW-3 and 4).

PMID- 11511720
TI  - Highly increased CSF tau protein and decreased beta-amyloid (1-42) in sporadic
      CJD: a discrimination from Alzheimer's disease?
AB  - The aim was to quantify tau protein and beta-amyloid (Abeta42) in the CSF of
      patients with sporadic Creutzfeldt-Jakob disease (CJD), Alzheimer's disease (AD),
      and controls. Double sandwich enzyme linked immunosorbent assays (ELISAs) were
      used for measurements. Tau was increased 58-fold in CJD and 3.5-fold in AD
      compared with controls, whereas Abeta42 was decreased 0.5-fold in both CJD and
      AD. A cut off level for tau protein at 2131 pg/ml successfully discriminated CJD
      from AD (100% specificity and 93% sensitivity). Tau protein concentration in CSF
      is probably an additional useful marker in differentiating CJD from AD.

PMID- 11511721
TI  - Combination of cyclophosphamide and interferon-beta halts progression in patients
      with rapidly transitional multiple sclerosis.
AB  - The effects of combined treatment with cyclophosphamide (CTX) and interferon-beta
      (IFN-beta) are described in selected patients with "rapidly transitional"
      multiple sclerosis. This form of multiple sclerosis is extremely active with very
      frequent and severe attacks which produce a dramatic increase on the expanded
      disability status scale (EDSS). Ten patients with rapidly transitional multiple
      sclerosis were previously treated with interferon-beta, but none benefited by
      this treatment. Monthly treatment with intravenous CTX, from 500 mg/m(2) to 1500
      mg/m(2) to obtain a chronic lymphocytopenia (600/mm(3) to 900/mm(3)) produced a
      marked and significant reduction in the number of relapses (p<0.0001), disability
      previously accumulated (p<0.0001), and a reduction of T2 MRI burden of lesion.
      This particular group of patients benefited by combining cyclophosphamide and IFN
      beta. The possibility is considered of carrying out further studies to test the
      efficacy of the association between the two drugs for patients who are not
      responsive to IFN-beta or other active disease modifying therapies.

PMID- 11511722
TI  - Willem Einthoven (1860-1927).

PMID- 11511723
TI  - Increased ictal perfusion of the thalamus in paroxysmal kinesigenic dyskinesia.
AB  - The ictal and interictal cerebral blood flow (CBF) were evaluated in a patient
      with right unilateral short lasting paroxysmal kinesigenic dyskinesia, by means
      of single photon emission computed tomography (SPECT). The patient was a 6 year
      old boy with no family history. During an attack, increased CBF was seen in the
      left thalamus. Subtraction of interictal CBF from ictal CBF disclosed a prominent
      increase in CBF in the left posterolateral part of the thalamus. This finding
      suggests that abnormal hyperactivity of thalamic neurons could be responsible for
      the pathophysiology of paroxysmal kinesigenic dyskinesia in this patient.

PMID- 11511724
TI  - Magnetic resonance imaging findings before and after treatment of spontaneous
      intracranial hypotension.

PMID- 11511732
TI  - Neurology in practice: sleep and coma.

PMID- 11511733
TI  - Locked-in syndrome.

PMID- 11511734
TI  - The sleepy patient.

PMID- 11511735
TI  - Assessing confused patients.

PMID- 11511736
TI  - Neurological assessment of coma.

PMID- 11511737
TI  - States related to or confused with coma.

PMID- 11511738
TI  - The prognosis of medical coma.

PMID- 11511739
TI  - An aid to predicting prognosis in patients with non-traumatic coma at one day.

PMID- 11511740
TI  - Permanent vegetative state and the law.

PMID- 11511741
TI  - Occupational seafood allergy: a review.
AB  - BACKGROUND: Recent years have seen increased levels of production and consumption
      of seafood, leading to more frequent reporting of allergic reactions in
      occupational and domestic settings. This review focuses on occupational allergy
      in the fishing and seafood processing industry. REVIEW: Workers involved in
      either manual or automated processing of crabs, prawns, mussels, fish, and
      fishmeal production are commonly exposed to various constituents of seafood.
      Aerosolisation of seafood and cooking fluid during processing are potential
      occupational situations that could result in sensitisation through inhalation.
      There is great variability of aerosol exposure within and among various jobs with
      reported allergen concentrations ranging from 0.001 to 5.061(microg/m(3)).
      Occupational dermal exposure occurs as a result of unprotected handling of
      seafood and its byproducts. Occupational allergies have been reported in workers
      exposed to arthropods (crustaceans), molluscs, pisces (bony fish) and other
      agents derived from seafood. The prevalence of occupational asthma ranges from 7%
      to 36%, and for occupational protein contact dermatitis, from 3% to 11%. These
      health outcomes are mainly due to high molecular weight proteins in seafood
      causing an IgE mediated response. Cross reactivity between various species within
      a major seafood grouping also occurs. Limited evidence from dose-response
      relations indicate that development of symptoms is related to duration or
      intensity of exposure. The evidence for atopy as a risk factor for occupational
      sensitisation and asthma is supportive, whereas evidence for cigarette smoking is
      limited. Disruption of the intact skin barrier seems to be an important added
      risk factor for occupational protein contact dermatitis. CONCLUSION: The range of
      allergic disease associated with occupational exposure to crab is well
      characterised, whereas for other seafood agents the evidence is somewhat limited.
      There is a need for further epidemiological studies to better characterise this
      risk. More detailed characterisation of specific protein antigens in aerosols and
      associated establishment of dose-response relations for acute and chronic
      exposure to seafood; the respective roles of skin contact and inhalational
      exposure in allergic sensitisation and cross reactivity; and the contribution of
      host associated factors in the development of occupational seafood allergies are
      important areas for future research.

PMID- 11511743
TI  - Hours of work and the risk of developing impaired fasting glucose or type 2
      diabetes mellitus in Japanese male office workers.
AB  - OBJECTIVE: To investigate the association between duration of overtime and the
      development of impaired fasting glucose (IFG) or type 2 diabetes mellitus (DM).
      METHODS: A cohort of 1266 Japanese male office workers aged 35-59 years and free
      of IFG (fasting plasma glucose concentration 6.1-6.9 mmol/l), type 2 DM (fasting
      plasma glucose concentration of 7.0 mmol/l or more or taking hypoglycaemic
      medication), history of diabetes, or medication for hypertension were re-examined
      over 5 successive years after their initial examinations in 1994. RESULTS: 138
      men developed IFG or type 2 DM during the 5736 person-years of follow up. After
      controlling for potential predictors of diabetes, the relative risks of IFG or
      type 2 DM, compared with those who worked <8.0 hours a day, were 0.82 (95%
      confidence interval (95% CI) 0.54 to 1.26), 0.69 (95% CI 0.38 to 1.26), 0.63 (95%
      CI: 0.37 to 1.09), and 0.50 (95% CI: 0.25 to 0.98) for those who worked 8.0-8.9,
      9.0-9.9, 10.0-10.9, and of 11.0 hours or more a day, respectively (p for
      trend=0.020). 87 and 54 men developed IFG and type 2 DM during the 5817 and 5937
      person-years of follow up, respectively. The multivariate adjusted relative risks
      of IFG tended to decrease with an increase in hours of overtime work a day, but
      did not reach significance (p for trend=0.202). On the other hand, the
      multivariate adjusted relative risks of type 2 DM significantly decreased with an
      increase in hours of overtime work a day (p for trend=0.014). CONCLUSION: Longer
      overtime is a negative risk factor for the development of IFG or type 2 DM in
      Japanese male office workers.

PMID- 11511742
TI  - Environmental tobacco smoke and lung function in employees who never smoked: the
      Scottish MONICA study.
AB  - OBJECTIVES: To investigate the relation between lung function in employees and
      exposure to environmental tobacco smoke (ETS) at work and elsewhere. METHODS:
      Never smokers in employment (301) were identified from the fourth Scottish MONICA
      survey. They completed a self administered health record, which included details
      of exposure to ETS, and attended a survey clinic for physical and lung function
      measurements, and for venepuncture for estimation of serum cotinine. Differences
      in lung function in groups exposed to ETS were tested by analysis of variance
      (ANOVA), the exposure-response relation by a linear regression model, and a case
      control analysis undertaken with a logistic regression model. RESULTS: Both men
      and women showed effects on forced expiratory volume in the first second (FEV(1))
      and forced vital capacity (FVC) from exposure to ETS-higher exposure going with
      poorer lung function. This was found at work, and in total exposure estimated
      from ETS at work, at home, and at other places. Linear regression showed an
      exposure-response relation, significant for ETS at work, total exposure, and
      exposure time/day, but not at home or elsewhere. Compared with those not exposed
      to ETS at work, those who were exposed a lot had a 254 ml (95% confidence
      interval (95% CI) 84 to 420) reduction in FEV(1), and a 273 ml (60 to 480)
      reduction in FVC after adjusting for confounders. Although lung function was not
      significantly associated with serum cotinine in all the data, a significant
      inverse relation between cotinine concentration and FVC occurred in men who had
      had blood collected in the morning. Case-control analysis also showed a
      significant exposure-response relation between ETS, mainly at work, and lung
      function. A higher exposure measured both by self report and serum cotinine went
      with lower lung function. CONCLUSION: The exposure-response relation shows a
      reduction in pulmonary function of workers associated with passive smoking,
      mainly at work. These findings endorse current policies of strictly limiting
      smoking in shared areas, particularly working environments.

PMID- 11511744
TI  - Survey of solvent related chronic encephalopathy as an occupational disease in
      European countries.
AB  - OBJECTIVES: To obtain information about solvent related chronic encephalopathy
      (SRCE) in the countries of the European Union (EU). METHOD: A survey was
      conducted in 1998 and 1999 among medical experts, authorities for health and
      safety, and social security institutions. RESULTS: SRCE is an acknowledged
      occupational disease in most of the participating countries. However, the numbers
      of compensated cases differ considerably. This is mainly a consequence of
      national social law rather than of differences in the criteria of diagnosis. In
      countries with relatively high reported incidences-such as Denmark, Finland,
      Norway, and Sweden-the number of acknowledged cases has declined over the past 5
      10 years, although the most important criteria of diagnosis and causality,
      according to expert opinion, equivalent diagnostic procedures, and measures for
      prevention within the EU are not comparable. CONCLUSIONS: There is a need for
      common guidelines for early diagnosis and the evaluation of causality. Actual
      figures of SRCE are not suitable to estimate prospective numbers of cases. For
      this reason a multicentre study in EU states is necessary after a consensus of
      diagnostic procedure. It is likely that the number of cases will decrease as a
      result of changes in legislation and preventive measures-such as substitution or
      reduction of solvents in the products, improvement of technical equipment, and
      regular health surveillance. Future research activities should focus on follow up
      studies of prognosis, randomised clinical trials of treatment, investigation of
      neurotoxic mechanisms, and of the interaction of solvent mixtures.

PMID- 11511745
TI  - Parkinsonism and occupational exposure to pesticides.
AB  - OBJECTIVE: To examine the risk of parkinsonism related to lifetime occupational
      exposure to pesticides among a cohort of men, mostly orchardists, in Washington
      State. METHODS: All 310 subjects in this study had previously participated in a
      cohort study of men occupationally exposed to pesticides. Subjects were given a
      structured neurological examination and completed a self administered
      questionnaire which elicited detailed information on pesticide (insecticide,
      herbicide, and fungicide) use throughout their working careers. Demographic
      characteristics were also sought. Subjects had a mean age of 69.6 years (range 49
      96, SD 8.1). There were 238 (76.8%) subjects who reported some occupational
      exposure to pesticides, whereas 72 (23.2%) reported none. Parkinsonism was
      defined by the presence of two or more of rest tremor, rigidity, bradykinesia,
      and impairment of postural reflexes in subjects not on antiparkinsonian
      medication, or the presence of at least one sign if they were on such medication.
      Parkinson's disease was not studied explicitly because of the difficulty in
      distinguishing it from other parkinsonian syndromes. A generalised linear model
      was used to estimate prevalence ratios (PRs) for parkinsonism relative to history
      of farming, pesticide use, and use of well water. RESULTS: A PR of 2.0 (95%
      confidence interval (95% CI) 1.0 to 4.2) was found for subjects in the highest
      tertile of years of exposure to pesticides; a similarly increased, non
      significant, PR was found for the middle tertile (1.9 (95% CI 0.9 to 4.0)),
      although a trend test did not show a significant exposure-response relation. No
      increased risks were found associated with specific pesticides or pesticide
      classes, nor with a history of farming or use of well water. CONCLUSION:
      Parkinsonism may be associated with long term occupational exposure to
      pesticides, although no associations with specific pesticides could be detected.
      This finding is consistent with most of the publications on this topic.

PMID- 11511746
TI  - Occupational risk factors for male bladder cancer: results from a population
      based case cohort study in the Netherlands.
AB  - OBJECTIVES: This study was conducted to estimate risk of bladder cancer
      associated with occupational exposures to paint components, polycyclic aromatic
      hydrocarbons (PAHs), diesel exhausts, and aromatic amines among the general
      population in The Netherlands. METHODS: A prospective cohort study was conducted
      among 58,279 men. In September 1986, the cohort members (55-69 years) completed a
      self administered questionnaire on risk factors for cancer including job history.
      Follow up for incident bladder cancer was established by linkage to cancer
      registries until December 1992. A case-cohort approach was used based on 532
      cases and 1630 subcohort members. A case by case expert assessment was carried
      out to assign to the cases and subcohort members a cumulative probability of
      occupational exposure for each carcinogenic exposure. RESULTS: Men in the highest
      tertiles of occupational exposure to paint components, PAHs, aromatic amines, and
      diesel exhaust had non-significantly higher age and smoking adjusted incident
      rate ratios (RRs) of bladder cancer than men with no exposure: 1.29 (95%
      confidence interval (95% CI) 0.71 to 2.33), 1.24 (95% CI 0.68 to 2.27), 1.32 (95%
      CI 0.41 to 4.23) and 1.21 (95% CI 0.78 to 1.88), respectively. The associations
      between paint components and PAHs and risk of bladder cancer were most pronounced
      for current smokers. Among former smokers it seemed that for cumulative
      probability of exposure to paint components and PAHs, men who had smoked more
      than 15 cigarettes a day had RRs below unity compared with men who had smoked
      less than 15 cigarettes a day, whereas among current smokers the opposite was
      found. Exposure to diesel exhaust was positively associated with risk of bladder
      cancer among current and former smokers who had smoked more than 15 cigarettes a
      day. CONCLUSIONS: This study provided only marginal evidence for an association
      between occupational exposure to paint components, PAHs, aromatic amines, and
      bladder cancer. Despite the small proportion of exposed subjects, an interaction
      with cigarette smoking was found, specifically for paint components, suggesting
      that the carcinogenic effect on the bladder might decrease after stopping
      smoking.

PMID- 11511747
TI  - Interrelations of risk factors and low back pain in scaffolders.
AB  - OBJECTIVES: To assess with a cross sectional study the interrelations between
      physical, psychosocial, and individual risk factors and different end points of
      low back pain. METHODS: In total, 229 scaffolders and 59 supervisors completed a
      questionnaire about manual handling of materials, awkward back posture, strenuous
      arm position, perceived exertion, psychosocial load, need for recovery, and
      general health. Physical load at the worksite was also measured with many
      frequent observations. Interrelations between risk factors and their relation
      with four end points of low back pain were investigated. RESULTS: Interrelations
      were strong among self reported determinants of physical load but showed an
      inverted trend for both age and total working experience, which could indicate
      the presence of a healthy worker effect. Weak relations existed between variables
      of psychosocial and physical load. The multivariate analyses showed a significant
      relation between high manual handling of materials, moderate perceived general
      health, high job demands, and low back pain in the past 12 months. Chronic low
      back pain was significantly correlated with high perceived exertion and moderate
      perceived general health. Severe low back pain was significantly correlated with
      awkward back postures, high need for recovery, and high job demands. Finally, low
      back pain with perceived disability was significantly related to strenuous
      shoulder positions and moderate perceived general health. All end points of low
      back pain were consistently associated with physical load whereas psychosocial
      aspects showed a more diverse pattern. CONCLUSIONS: The findings of this study
      suggest that work related risk factors may vary according to different
      definitions of low back pain. Distinct patterns of risk factors might enhance
      different expressions of it. Scaffolders are a group at high risk of developing
      persistent forms of low back pain.

PMID- 11511748
TI  - What happens to the manuscripts that have not been accepted for publication in
      Occupational and Environmental Medicine?
AB  - OBJECTIVES: To evaluate the fate of manuscripts rejected by Occupational and
      Environmental Medicine (OEM). METHODS: A Medline search was conducted, up to
      March 2001, to find out whether and where articles submitted to OEM in 1995,
      1996, and 1997, but not accepted for publication, were published. The articles
      were matched by authors and title, sometimes using the abstract to help decide
      whether the published article was the one that had been previously submitted to
      OEM. RESULTS: Out of 405 manuscripts rejected (44% of those submitted), 218
      articles (54%) were traced in 72 different journals, with more than half being
      published in seven other major journals dealing with occupational and
      environmental health (rather than in specialty journals). Most papers were
      published within 2 years of their initial submission to OEM. Only a small
      proportion (10%) were published in a journal with a higher impact factor than OEM
      (1.96 in 1999). CONCLUSION: More than half the articles rejected by OEM found
      their way into the scientific literature covered by Medline. This figure is
      comparable with the few available data from other journals. It would be
      interesting to know the fate of articles published by OEM before they were
      submitted to our journal.

PMID- 11511750
TI  - From protocols to principles, from guidelines to toolboxes: aids to good
      management of osteoarthritis.

PMID- 11511749
TI  - Occupational methaemoglobinaemia.

PMID- 11511751
TI  - Responsiveness of the Cochin rheumatoid hand disability scale after surgery.
AB  - OBJECTIVE: To assess the responsiveness of the Cochin functional disability scale
      for the rheumatoid hand after surgery. METHOD: In a prospective study, patients
      with rheumatoid arthritis (RA) scheduled for surgery of the wrist and/or fingers
      were evaluated within 48 h before surgery and at least 6 months after surgery.
      Clinical outcome measures included duration of morning stiffness, total score for
      tenderness, total score for swelling, visual analogue scale score for pain in the
      hands and wrists, a score for overall mobility of the wrist and the fingers, grip
      and pinch strength, the Hand Functional Index (HFI), the Kapandji index and the
      Cochin scale. Responsiveness was assessed with the paired t-test, the effect size
      (ES), the standardized response mean (SRM) and the non-parametric Spearman rank
      correlation coefficient (r(S)). RESULTS: Fifty patients (42 women) were evaluated
      twice at an interval of 7.16 +/- 2.10 months (mean +/- s.d.) (range 6-15 months).
      Thirty-six patients (72%) were very satisfied or satisfied with the results of
      surgery, seven (14%) were not satisfied or dissatisfied and seven (14%) were
      dissatisfied or very dissatisfied. The Cochin scale score improved at the second
      visit (P < 0.0001), with SRM and ES values of 0.66 and 0.58 respectively. The
      correlation of the change in Cochin score with patient overall satisfaction was
      r(S) = 0.40. Among the impairment measures, grip strength showed the best
      responsiveness (SRM = - 0.43, ES = - 0.36, correlation with patient overall
      satisfaction r(S) = 0.46). The change in Kapandji index had the best correlation
      (r(S) = 0.51) with patient overall satisfaction but its SRM and ES values were
      low (- 0.19 and - 0.10 respectively). CONCLUSION: The Cochin scale is responsive
      and appropriate for the assessment of the effects of surgical treatments on
      disability in RA hands.

PMID- 11511752
TI  - Monoclonal anti-double stranded DNA antibody is a leucocyte-binding protein to up
      regulate interleukin-8 gene expression and elicit apoptosis of normal human
      polymorphonuclear neutrophils.
AB  - OBJECTIVES: To determine whether anti-double stranded DNA (anti-dsDNA)
      autoantibody could bind and affect the functions of normal human
      polymorphonuclear neutrophils (PMN). METHODS: Normal human PMN were incubated
      with different concentrations of a monoclonal mouse anti-dsDNA antibody (12B3) or
      mouse isotype-matched IgG2a. The binding of anti-dsDNA and PMN was measured by
      flow cytometry and interleukin-8 (IL-8) gene expression in PMN was detected by
      enzyme-linked immunosorbent assay (ELISA) and reverse transcription-polymerase
      chain reaction (RT-PCR). PMN apoptosis was justified by morphological changes.
      The cognate antigen(s) of anti-dsDNA on the PMN surface was identified by
      membrane biotinylation, immunoprecipitation and Western blot. RESULTS: The
      binding of PMN with anti-dsDNA was much higher than with non-specific mouse IgG2a
      (70.8 vs 2.0%). Anti-dsDNA at concentrations higher than 12.5 ng/ml significantly
      enhanced the production and mRNA expression of IL-8 by PMN. However, anti-dsDNA
      facilitated PMN apoptosis after 3 h incubation. Western blot analysis of
      biotinylated PMN cell lysates demonstrated that a 50-52 kDa membrane molecule is
      the cognate antigen of anti-dsDNA. CONCLUSIONS: Anti-dsDNA autoantibody up
      regulates IL-8 gene expression and elicits activation-induced cell death (AICD)
      of human PMN via binding to a 50-52 kDa membrane-expressed molecule.

PMID- 11511753
TI  - Pain referral from the sternoclavicular joint: a study in normal volunteers.
AB  - OBJECTIVE: The sternoclavicular joint (SCJ) is commonly affected by
      rheumatological conditions. Case reports suggest that it may refer pain to
      distant areas, potentially leading to delays in diagnosis and inappropriately
      targeted investigations. Therefore, we studied the patterns of pain referral from
      the SCJ of nine healthy volunteers. METHODS: Hypertonic saline was injected into
      the SCJ of nine normal volunteers and the location of any resulting pain was
      noted, as was the effect of resisted shoulder abduction and flexion. Composite
      pain maps were then constructed from individual pain diagrams. RESULTS: An
      unpleasant, deep aching pain was produced locally in eight subjects and referred
      to distant sites in all subjects. Tests of shoulder movement had varied and
      inconstant effects. CONCLUSIONS: We demonstrated that the SCJ is capable of
      referring pain to areas distant from the joint. Knowledge of these referral
      patterns will enable the SCJ to be considered in patients with pain in these
      areas.

PMID- 11511754
TI  - Comparison of renal disease severity and outcome in patients with primary
      antiphospholipid syndrome, antiphospholipid syndrome secondary to systemic lupus
      erythematosus (SLE) and SLE alone.
AB  - OBJECTIVE: To ascertain the clinical presentation, histopathology and outcome of
      renal involvement in patients with primary antiphospholipid syndrome (PAPS),
      antiphospholipid syndrome secondary to systemic lupus erythematosus (SAPS) and
      systemic lupus erythematosus alone. METHOD: A retrospective analysis was
      undertaken of 20 patients with PAPS, 25 patients with SAPS and 275 patients with
      systemic lupus erythematosus to ascertain the frequency and pattern of renal
      involvement. RESULTS: Renal involvement was found most frequently in patients
      with SAPS, in whom it occurred in 68% of patients. Renal disease was equally
      common in patients with PAPS and systemic lupus erythematosus alone where it was
      seen in 30% of patients. Patients with systemic lupus erythematosus most
      frequently presented with nephrotic syndrome due to glomerulonephritis, whereas
      those with PAPS and SAPS were more likely to present with hypertension and
      reduced glomerular filtration rate. No patients with PAPS developed end-stage
      renal failure compared with 5.9% of patients with SAPS and 16.9% of patients with
      systemic lupus erythematosus alone; 23.5% of patients with SAPS died compared
      with 15.7% of patients with systemic lupus erythematosus alone and no patients
      with PAPS. CONCLUSION: Renal involvement is a major feature of both PAPS and
      SAPS, where renal thrombosis frequently leads to reduced glomerular filtration
      rate and hypertension. One-third of patients with systemic lupus erythematosus
      alone develop glomerulonephritis leading to renal disease which most commonly
      presents with nephrotic syndrome. Patients with PAPS were less likely to develop
      end-stage renal failure or die during the follow-up period.

PMID- 11511755
TI  - Systemic lupus erythematosus and rheumatoid arthritis patients differ from
      healthy controls in their cytokine pattern after stress exposure.
AB  - OBJECTIVE: To study whether patients with rheumatoid arthritis (RA) or systemic
      lupus erythematosus (SLE) differ from healthy individuals in their immune
      responses to acute psychological stress. METHODS: The phenotype and function of
      peripheral blood lymphocytes were analysed before and after stress exposure in
      patients and healthy subjects. RESULTS: Natural killer (NK) cell numbers
      increased transiently in all groups under stress. NK activity, however, increased
      in healthy controls only. We observed a stress-induced increase in interleukin
      (IL)-4-producing (IL-4(+)) cells in SLE patients only, whereas interferon (IFN)
      gamma(+) cell numbers increased due to stress in all three groups. An analysis of
      supernatants from phytohaemagglutinin (PHA) cultures revealed increased IFN gamma
      and IL-10 levels in healthy subjects but not in SLE or RA patients after stress
      exposure. CONCLUSIONS: These data demonstrate that RA and SLE patients differ in
      their immune response to stress from healthy controls. Changes in cytokine
      patterns might be responsible for stress-induced exacerbation of disease activity
      in RA and SLE patients.

PMID- 11511756
TI  - Serum interleukin-15 is elevated in systemic lupus erythematosus.
AB  - OBJECTIVE: To investigate if interleukin-15 (IL-15) (rather than IL-2) is
      increased in systemic lupus erythematosus (SLE) and might be responsible for
      immunological abnormalities of SLE such as the increased lymphocytic expression
      of Bcl-2 and CD25. METHODS: Serum IL-15, IL-2 and tumour necrosis factor (TNF)
      levels of 65 SLE patients, 20 healthy persons and 10 rheumatoid arthritis (RA)
      patients were measured by enzyme-linked immunosorbent assay (ELISA). For 25 SLE
      patients, the percentage of CD25 + lymphocytes and the lymphocytic Bcl-2 levels
      were simultaneously determined by fluorocytometry. Peripheral blood mononuclear
      cells (PBMC) of 15 SLE patients were incubated with or without recombinant IL-15
      and the influence on Bcl-2 and CD25 was determined. RESULTS: IL-15 was found to
      be elevated in 25 SLE sera (38%), but in none of the 20 healthy sera (P = 0.0005)
      and none of the 10 RA sera. Both lymphocyte CD25 and Bcl-2 expression
      significantly correlated with serum IL-15 and were increased by recombinant IL
      15. CONCLUSION: Serum IL-15 may in part be responsible for the immunological
      abnormalities seen in active SLE.

PMID- 11511757
TI  - Bone density, ultrasound measurements and body composition in early ankylosing
      spondylitis.
AB  - OBJECTIVES: In this cross-sectional study, we evaluated bone density using both
      dual-energy X-ray absorptiometry (DEXA) and quantitative ultrasound (QUS)
      techniques and examined the changes in body composition in patients with
      ankylosing spondylitis (AS). METHODS: Seventy-one patients were compared with
      seventy-one sex- and age-matched controls. Bone mineral density (BMD) was
      evaluated at the lumbar spine and femoral neck with a Lunar device. Total body
      measurements were also performed, giving BMD and bone mineral content (BMC) of
      the whole body, and fat and lean masses. Broadband ultrasound attenuation (BUA),
      speed of sound and stiffness were measured at the calcaneus using an Achilles
      ultrasound device. RESULTS: The patients had significantly lower lumbar spine,
      femoral neck and total body BMD as compared with controls (all P < 0.05). Total
      body BMC was also decreased in AS (P = 0.002). On the contrary, fat and lean
      masses did not differ between patients and controls as observed for QUS values.
      Mild to good correlations were found between BMD and QUS parameters (r ranging
      from 0.22 to 0.53; all P < or = 0.01). When applying the World Health
      Organization (WHO) definition for osteoporosis, we found that 46.5% of patients
      had lumbar spine osteopenia and/or osteoporosis, while 26.8% had femoral neck
      osteopenia and/or osteoporosis (controls: 23.9 and 10%; P = 0.001 and 0.08,
      respectively). No relationships between disease activity (as evaluated by
      erythrocyte sedimentation rate, serum C-reactive protein levels and BASDAI, a
      clinical index of disease activity) and BMD measurements were found and only
      femoral neck BMD correlated with disease duration (r = -0.25; P = 0.04). Finally,
      the presence of talalgia in AS did not influence the QUS values. CONCLUSION:
      These results confirm that AS patients have decreased BMD values at both the
      spine and femur, and also in total body measurements, reflecting a generalized
      bone loss. On the contrary, soft tissue composition does not seem to be
      influenced by the disease. QUS parameters were found to be similar between
      patients and controls, suggesting that the QUS method did not provide additive
      information to DEXA. As it is thought that QUS provides information about
      qualitative properties of bone, the normal results of QUS values in our patient
      series argue against modifications in AS bone micro-architecture.

PMID- 11511758
TI  - Limited endothelial E- and P-selectin expression in MRL/lpr lupus-prone mice.
AB  - OBJECTIVE: Inflammation in MRL/lpr mice may involve dysfunctional leucocyte
      endothelial cell (EC) interactions. Previously, we have shown that intercellular
      adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1)
      increase with age in a tumour necrosis factor alpha (TNF alpha)- and interleukin
      1 (IL-1)-dependent manner. The object of this study was to determine the
      expression of E- and P-selectin. METHODS: Selectin expression was quantified in
      MRL/lpr mice and BALB/c controls by intravenous injection of differentially radio
      labelled antibodies. RESULTS: E-selectin, but not P-selectin, was up-regulated in
      the kidneys of older mice. Neither was up-regulated elsewhere. There was no
      defect in selectin inducibility, as a further inflammatory stimulus
      (intraperitoneal lipopolysaccharide) resulted in up-regulation. Serum from older
      MRL/lpr did not induce selectin expression by EC in vitro. CONCLUSION: The
      increase in E-selectin in the kidney may contribute to the development of
      glomerulonephritis. However, the lack of systemic E- and P-selectin expression
      may represent a protective mechanism which limits the interaction between
      leucocytes and the endothelium in the chronic inflammatory context.

PMID- 11511759
TI  - Outcome measures and classification criteria for the rheumatic diseases. A
      compilation of data from OMERACT (Outcome Measures for Arthritis Clinical
      Trials), ILAR (International League of Associations for Rheumatology), regional
      leagues and other groups.

PMID- 11511760
TI  - Efficacy and safety profile of cyclosporin A in the treatment of juvenile chronic
      (idiopathic) arthritis. Results of a 10-year prospective study.
AB  - OBJECTIVE: This open prospective trial was performed in order to assess the
      efficacy and safety of cyclosporin A in the treatment of patients with juvenile
      chronic arthritis (JCA). METHODS: Thirty-four of the patients enrolled were
      affected by systemic-onset disease and seven by chronic anterior uveitis
      associated with JCA. The cyclosporin dose was usually 3-5 mg/kg per day. The
      average duration of therapy was 1.4 yr, with a maximum of 7.2 yr. RESULTS: The
      efficacy of treatment was mainly evident in terms of control of fever and
      reduction of steroid therapy. The benefits with respect to arthritis, laboratory
      parameters and uveitis seemed to be less clear-cut. Side-effects were frequent
      but usually mild or reversible. Sixty-six per cent of the study population
      withdrew from therapy because of inefficacy or side-effects. Eight systemic
      patients withdrew from therapy owing to complete remission. CONCLUSION:
      Cyclosporin can be used in the treatment of JCA, its main benefits being the
      control of fever and a steroid-sparing effect.

PMID- 11511761
TI  - Discordance between proxy-reported and observed assessment of functional ability
      of children with juvenile idiopathic arthritis.
AB  - OBJECTIVE: To determine the level of agreement between parents and clinicians in
      rating dysfunction in children with juvenile idiopathic arthritis (JIA). METHODS:
      A parent of each patient completed the Italian version of the Childhood Health
      Assessment Questionnaire (CHAQ). Subsequently, an examiner assessed, in a
      specially equipped room, the child's performance of tasks as described by the
      CHAQ. Demographic and clinical variables were recorded for all patients. RESULTS:
      Seventy consecutive JIA patients and their parents were included. The mean proxy
      reported and observed CHAQ score was 0.64+/-0.53 and 0.47+/-0.62 respectively,
      the difference ranging from -1.75 to 1.5. There were 30 cases (43%) of agreement
      (difference < or =0.25 CHAQ units) between the parent's and clinician's ratings,
      whereas in 40 cases (57%) there was discordance (difference >0.25 CHAQ units). In
      30 cases the parent rated the child's functional ability as worse than that
      observed by the clinician (i.e. the parent underestimated the child's function),
      whereas in 10 cases the parent rated the child's functional ability as better
      than that observed by the clinician (i.e. overestimated the child's function).
      Multivariate regression analysis showed that children's functional ability was
      overestimated by parents with increasing erythrocyte sedimentation rate and
      global articular severity score and underestimated with increasing level of pain.
      Among the functional areas of the CHAQ, the level of agreement was poorest in the
      areas of eating and hygiene and was best for activities. CONCLUSIONS: Discordance
      between proxy-reported and observed functional ability was frequent in our
      patients with JIA. The children's functional ability was overestimated by parents
      as the severity of arthritis increased and underestimated as the level of pain
      increased.

PMID- 11511762
TI  - Bacterial DNA in synovial fluid cells of patients with juvenile onset
      spondyloarthropathies.
AB  - OBJECTIVE: To identify bacterial DNA in synovial fluid cells of patients with
      active juvenile onset spondyloarthropathy (SpA). METHODS: The main group of study
      constituted 22 patients with juvenile onset SpA. In addition, five patients with
      adult onset SpA and nine with rheumatoid arthritis (RA) were studied. Polymerase
      chain reaction (PCR) with either genus- or species-specific primers was performed
      on synovial fluid cells to detect DNA sequences of Chlamydia trachomatis,
      Yersinia enterocolitica, Salmonella sp., Shigella sp., Campylobacter sp. and
      Mycobacterium tuberculosis. The presence of antibacterial antibodies in sera and
      synovial fluid was also determined by enzyme-linked immunoassay. RESULTS: The
      synovial fluid of nine patients with juvenile onset SpA, three with adult onset
      SpA and one with RA contained bacterial DNA. Five juvenile onset SpA samples had
      DNA of one single bacterium; two juvenile onset SpA and three adult onset SpA had
      DNA of two bacteria and two juvenile onset SpA had DNA of three bacteria.
      Overall, Salmonella sp. DNA was detected in seven synovial fluid samples,
      Shigella sp., Campylobacter sp. and M. tuberculosis were found in four samples
      each, and C. trachomatis was found in two. The bacterial DNA findings correlated
      with neither diagnosis nor disease duration. One RA synovial fluid had DNA of
      Campylobacter sp. Neither serum nor synovial fluid antibacterial antibodies
      correlated with DNA findings or clinical diagnosis. CONCLUSION: In this study,
      single and several combinations of bacterial DNA were identified in the synovial
      fluid of patients with long-term undifferentiated and definite juvenile onset SpA
      and adult onset SpA. Of relevance is that bacterial DNA corresponds to bacteria
      producing endemic disease in our population.

PMID- 11511763
TI  - Changes in the incidence of juvenile rheumatoid arthritis in Finland.
AB  - OBJECTIVE: To study trends in the incidence of juvenile rheumatoid arthritis
      (JRA). METHODS: The study covered subjects who were entitled under the nation
      wide sickness insurance scheme to receive specially reimbursed medication for
      juvenile rheumatic diseases in 11 of 21 central hospital districts in Finland
      (the base population comprised about 445,000 children <16 yr of age) in 1995.
      Data from the years 1980, 1985 and 1990 were compared with data from 1995
      concerning the central part of the area, which had been included in a previous
      study by us. RESULTS: A total of 87 incident cases (58 girls and 29 boys)
      satisfied criteria for JRA in 1995 in the study area. The incidence of JRA was
      19.5 per 100 000 [95% confidence interval (CI) 15.6-24.1] of the population <16
      yr of age for the whole area. It was 22.7 per 100,000 (95% CI 17.3-29.2) for the
      area that had been covered by the earlier study (five districts) and 14.9 per
      100,000 (95% CI 9.8-21.7) for the new area (six additional districts). The
      incidence of JRA was significantly higher than in the earlier years (1980, 1985
      and 1990) in the same district (trend, P=0.024). The highest incidence, 60.3 per
      100,000 (95% CI 35.8-95.4), was noted in 1995 among girls in the age group 10-15
      yr in the southernmost part of the study area. CONCLUSIONS: There was both
      temporal and regional variation in the incidence of JRA. Results of the present
      study suggest that environmental factors may influence the frequency of JRA.

PMID- 11511764
TI  - Behcet's disease in UK children: clinical features and treatment including
      thalidomide.
AB  - OBJECTIVE: To study the clinical spectrum of Behcet's disease (BD) in childhood,
      and to report our experience of using thalidomide. METHOD: Ten children,
      diagnosed with BD, were studied retrospectively. RESULTS: The median (range) age
      at first presentation was 4 (1.2-12.0) yr, at diagnosis was 11 (3-15) yr and the
      follow-up period was 4.1 (0.6-6.3) yr. Oral ulcers were present in all patients
      (100%), genital ulcers were present in six (60%), peri-anal ulcers were present
      in three (30%), skin manifestations were present in nine (90%), intracranial
      hypertension was present in two (20%), mild gastrointestinal symptoms were
      present in five (50%), joint symptoms were present in six (60%), ocular lesions
      were present in five (50%), but only one child had anterior and posterior
      uveitis. Therapeutically, a range of drugs was used, including colchicine, that
      resulted in good responses in five children. Thalidomide (1 mg/kg/week to 1
      mg/kg/day) was used in five children who were unresponsive to other
      immunosuppressive agents. It resulted in complete remission in three children and
      less frequent milder oral ulcers in two. Neuropathy developed in two children and
      in one it was irreversible. CONCLUSION: BD in children is similar to the disease
      in adults. Thalidomide provided a useful therapeutic option for severe oral and
      genital ulceration which was unresponsive to other therapies. Awareness of the
      danger of axonal neuropathy and teratogenesis at all times during thalidomide
      therapy is crucial. A low dose is probably as effective as higher doses.

PMID- 11511765
TI  - A normal ECG at birth does not exclude significant congenital cardiac conduction
      disease associated with maternal anti-Ro antibodies.

PMID- 11511766
TI  - Acquired deficiency of von Willebrand factor-cleaving protease in a patient
      suffering from acute systemic lupus erythematosus.

PMID- 11511767
TI  - Juvenile idiopathic arthritis associated with autoimmune thyroid disorders and
      autoimmune cholangitis.

PMID- 11511768
TI  - Amyloidosis in a series of 964 Portuguese rheumatoid arthritis patients: comment
      on the article by Myllykangas-Luosujarvi et al.

PMID- 11511769
TI  - Effective control of incomplete reactive arthritis with cyclosporin.

PMID- 11511770
TI  - Re: NSAIDS and simple analgesics.

PMID- 11511771
TI  - Superficial calcinosis related to bleeding in a patient with undifferentiated
      connective tissue disease and primary biliary cirrhosis.

PMID- 11511772
TI  - Autoimmune neutropenia, thrombocytopenia and Coombs positivity in a patient with
      primary Sjogren's syndrome.

PMID- 11511773
TI  - Disseminated nocardiosis presenting as a flare of Behcet's disease.

PMID- 11511774
TI  - Dysphagia and stridor caused by laryngeal rheumatoid arthritis.

PMID- 11511775
TI  - Unilateral submandibular swelling as unique presentation of Wegener's
      granulomatosis.

PMID- 11511776
TI  - Colour Doppler ultrasound of the nailbed: an objective tool for monitoring
      responses to vasodilatory treatment of connective tissue disorders?

PMID- 11511777
TI  - Successful treatment of 'malignant rheumatoid arthritis' in Japan with pooled
      intravenous immunoglobulin.

PMID- 11511778
TI  - Idiopathic orbital inflammation following intravenous pamidronate.

PMID- 11511780
TI  - Typing and antimicrobial susceptibilities of methicillin resistant Staphylococcus
      aureus (MRSA) strains isolated in a hospital in Korea.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) strains may cause serious
      nosocomial infections, including pneumonia and septicemia. The rate of
      methicillin-resistance among S. aureus isolates in Korea is over 50%. In this
      study, 90 MRSA isolates from Kyung Hee University Hospital were characterized
      employing bacteriophage typing, pulsed-field gel electrophoresis (PFGE), and
      antimicrobial susceptibility testing. Eighty percent of the strains could be
      phage-typed. The largest group or 40% of the strains belonged to lyso group III,
      followed by 32% of the isolates which produced a reaction with regional
      additional phages. Phage type 83A was most frequently encountered, followed by
      phage type D11. PFGE patterns confirmed the presence of two major clusters, which
      comprise the isolates belonging to lyso group III and the strains that were
      typable with regional additional phages. The latter group also contained a number
      of strains that were nontypable with bacteriophages. The resistance rates to
      ciprofloxacin, erythromycin, tetracycline, gentamicin and clindamycin were over
      94%. Strains with intermediate resistance to vancomycin strains or resistance to
      mupirocin were not found. In conclusion, this study demonstrates that the results
      of phage typing are confirmed and supplemented by PFGE data.

PMID- 11511781
TI  - Effect of high fat diet on insulin resistance: dietary fat versus visceral fat
      mass.
AB  - The purpose of the present study was to determine whether chronic high-fat diet
      (HF) induces insulin resistance independently of obesity. We randomly divided 40
      rats into two groups and fed them either with a HF or with a high-carbohydrate
      diet (HC) for 8 weeks. Whole body glucose disappearance rate (Rd) was measured
      using a euglycemic hyperinsulinemic clamp. Firstly, we defined whether insulin
      resistance by HF was associated with obesity. Plasma glucose and triglyceride
      concentrations were significantly increased in HF. Rd was decreased (10.6+/-0.2
      vs. 9.1+/-0.2 mg/kg/min in HC and HF, respectively) and the hepatic glucose
      output rate (HGO) was increased in HF (2.2+/-0.3 vs. 4.5+/-0.2 mg/kg/min in HC
      and HF, respectively). Rd was significantly correlated with %VF (p<0.01). These
      results implicate that visceral obesity is associated with insulin resistance
      induced by HF. In addition, to define whether dietary fat induces insulin
      resistance regardless of visceral obesity, we compared Rd and HGO between groups
      1) after matching %VF in both groups and 2) using an ANCOVA to adjust for %VF.
      After matching %VF, Rd in HF was significantly decreased by 14% (p<0.001) and HGO
      was significantly increased by 110% (p<0.001). Furthermore, statistical analyses
      using an ANCOVA also showed Rd for HF was significantly decreased even after
      adjusting %VF. In conclusion, we suggest that dietary fat per se could induce
      insulin resistance in rats fed with chronic HF independently of obesity.

PMID- 11511782
TI  - Obesity as a risk factor for non-insulin-dependent diabetes mellitus in Korea.
AB  - Most Korean patients with non-insulin-dependent diabetes mellitus (NIDDM) have
      been reported not to be obese, and many of them lost weight significantly during
      the course of their disease. In this regard, a retrospective cohort study was
      conducted to determine the relationship between body mass index (BMI, kg/m2) and
      the risk for NIDDM among Koreans. Subjects who had received a medical examination
      from 1990 to 1991 and who were available for the detection of NIDDM until
      September 1999 were included. Subjects who initially had diabetes or were
      diagnosed as diabetic within 1 yr after enrollment were excluded. We reviewed the
      medical records of final cohort of 2,531 subjects. Follow-up of this cohort
      revealed 117 cases with diabetes with an incident of 7.8 per 1,000 person-years.
      Compared with those with BMI less than 23 kg/m2, the adjusted relative risks for
      diabetes mellitus for those with BMI of 23-24.9, 25-26.9, and greater than 27
      kg/m2 were 0.85 (0.47-1.50), 1.29 (0.72-2.31), and 3.38 (1.22-4.63),
      respectively, for men (p for trend<0.01) and as for 9.14 (1.99-41.8), 7.36 (1.47
      36.8), and 14.5 (3.03-69.2), respectively, for women (p for trend<0.01). These
      data indicate a direct relationship between obesity and the risk for the
      development of diabetes, emphasizing the importance of weight control for the
      prevention of NIDDM in Koreans.

PMID- 11511783
TI  - Expression of NF-kappaB and cytokines in chronic rejection of transplanted murine
      heart.
AB  - The heart transplantation-associated accelerated graft arteriosclerosis (AGAS) is
      one of the major causes of cardiac allograft failure. We investigated the early
      time-course of expresssion patterns of cytokines, transcription factor, and its
      inhibitor in the intraabdominally transplanted mice hearts that differed only in
      the D locus of class I histocompatibility antigen. The allograft hearts were
      harvested at 1-3, 5, 7, 14, 28, and 42 days after the transplantation, and the
      expressions of NF-kappaB/I-kappaB and cytokines (TNF-alpha, INF-gamma) were
      examined in these specimens. The expressions of TNF-alpha and INF-gamma were
      observed on day 1, peaking on day 5 and 7, respectively. Activated NF-kappaB
      (p65) expression was present on the cytoplasm and perinuclear area in the
      endothelial cells of coronary arteries on day 1. The peak of translocation of NF
      B from cytoplasm to nucleus appeared on day 5 in the endothelial cells, myocytes,
      and leukocytes within the vessels, and remained elevated until day 42. The I
      kappaB expression gradually increased from day 1 until day 5, but a remarkable
      decrease was detected on day 7. Our data suggest that the increased expressions
      of NF-kappaB/I-kappaB and cytokines (TNF-alpha, INF-gamma) play an important role
      in inducing immune responses in the donor allograft heart and hence the blockage
      of the expressions might be mandatory to avoid a potential graft failure.

PMID- 11511784
TI  - Increased levels of circulating autoantibodies to cultured human bronchial
      epithelial cell in adult patients with nonatopic asthma.
AB  - The pathogenetic mechanism of nonatopic asthma has not yet been defined. The idea
      of a possible involvement of autoimmunity in the pathogenesis of nonatopic asthma
      has been proposed by earlier studies. To evaluate the possible involvement of
      autoimmune response against bronchial epithelial cell in the pathogenesis of
      nonatopic asthma, we measured circulating autoantibodies to cultured human
      bronchial epithelial cell (BEAS-2B cell line) using enzyme-linked immunosorbent
      assay. We used stored serum samples form 38 age-matched healthy controls, 26
      adult patients with atopic asthma, 16 adult patients with nonatopic asthma, and
      12 adult patients with systemic lupus erythematosus. Levels of IgG autoantibodies
      to bronchial epithelial cell were significantly higher in patients with nonatopic
      asthma (mean+/-SD of absorbance values; 0.135+/-0.030) and systemic lupus
      erythematosus (0.293+/-0.181) than in healthy controls (0.112+/-0.016) and
      patients with atopic asthma (0.116+/-0.031) (p<0.05). This study showed that
      levels of circulating IgG autoantibodies to bronchial epithelial cell were
      increased in adult patients with nonatopic asthma. Further studies are needed to
      evaluate the possible involvement of autoimmune mechanism in the pathogenesis of
      nonatopic asthma.

PMID- 11511785
TI  - Relationship between sputum inflammatory markers and osmotic airway
      hyperresponsiveness during induction of sputum in asthmatic patients.
AB  - Hypertonic saline aerosols are being used increasingly for bronchial provocation
      testing and induction of sputum. The aims of this study were to assess the
      response to challenge with 3% hypertonic saline administered via a ultrasonic
      nebulizer in patients with asthma, and to evaluate relationship between % fall of
      FEV1 during induction of sputum (osmotic airway hyperresponsiveness; osmotic AHR)
      and biochemical markers of induced sputum. We investigated changes in FEV1 in
      response to inhaling ultrasonically nebulized 3% saline in 25 patients with
      asthma and 10 control subjects. FEV1 was measured before, during, and after
      induction of sputum. We used fluoroimmunoassay to detect eosinophil cationic
      protein (ECP), immunohistochemical staining to detect EG2+ (secretory form of
      ECP) eosinophils, and a sandwich ELISA to detect interleukin (IL)-5. Protein
      concentration was determined by using bicinchoninic acid protein assay reagent.
      Asthmatics, compared with controls, had significantly higher osmotic AHR.
      Moderate to severe asthmatics had significantly higher osmotic AHR compared to
      mild asthmatics. Osmotic AHR was significantly correlated with the proportion of
      eosinophils, the levels of ECP, EG2+ eosinophils, IL-5, and proteins. These data
      suggest that osmotic AHR is closely related to the clinical status and
      biochemical markers of sputum supernatant in asthmatic patients.

PMID- 11511786
TI  - The relationship between microvessel count and the expression of vascular
      endothelial growth factor, p53, and K-ras in non-small cell lung cancer.
AB  - Using immunohistochemical staining, we studied the relationship between the
      microvessel count (MC) and the expression of K-ras, mutant p53 protein, and
      vascular endothelial growth factor (VEGF) in 61 surgically resected non-small
      cell lung cancers (NSCLC) (42 squamous cell carcinoma, 14 adenocarcinoma, 2 large
      cell carcinoma, 2 adenosquamous carcinoma, and 1 mucoepidermoid carcinoma). MC of
      the tumors with lymph node (LN) metastasis was significantly higher than that of
      tumors without LN metastasis (66.1+/-23.1 vs. 33.8+/-13.1, p<0.05). VEGF was
      positive in 54 patients (88.5%). MC was 58.1+/-25.2 (mean+/-S.D.) in a x200
      field, and it was significantly higher in VEGF(+) tumors than in VEGF(-) tumors
      (61.4+/-23.7 vs. 32.9+/-23.8, p<0.05). VEGF expression was higher in K-ras
      positive or mutant p53-positive tumors than in negative tumors (p<0.05). MC was
      significantly higher in K-ras(+) tumors than in K-ras(-) tumors, although it did
      not differ according to the level of mutant p53 protein expression. Survival did
      not differ with VEGF, mutant p53, or K-ras expression, or the level of MC. In
      conclusion, there is a flow of molecular alterations from K-ras and p53, to VEGF
      expression, leading to angiogenesis and ultimately lymph node metastasis.
      Correlations between variables in close approximation and the lack of prognostic
      significance of individual molecular alterations suggest that tumorigenesis and
      metastasis are multifactorial processes.

PMID- 11511787
TI  - Expression of the G1-S modulators in hepatitis B virus-related hepatocellular
      carcinoma and dysplastic nodule: association of cyclin D1 and p53 proteins with
      the progression of hepatocellular carcinoma.
AB  - Deranged expression of cell cycle modulators has been reported to contribute to
      the development and progression of hepatocellular carcinoma (HCC). However, their
      expression patterns remain poorly understood in hepatitis B virus (HBV)-related
      HCC, which constitutes about 65-70% of HCC in Korea. The aims of this study were
      to evaluate the expressions of G1-S modulators in HBV-related HCCs and dysplastic
      nodules (DNs), and to correlate with the histopathologic features of HCCs.
      Immunohistochemical expressions of cyclin D1, cyclin E, p53, p27, p21, p16, Rb,
      and PCNA proteins were investigated in 80 HCCs and 22 DNs. Cyclin D1
      overexpression showed positive relationships with advanced tumor stage, poor
      differentiation, larger tumor size, microvascular invasion, intrahepatic meta
      stasis, no tumor capsule formation, infiltrative growth, aberrant p53 expression,
      and high PCNA labeling index (LI) of HCC (p<0.05). Aberrant p53 expression showed
      positive relationship with poor differentiation of HCC (p<0.01). Expression of
      cyclin D1 or p53 was not observed in DNs. The p27 LI and p16 LI were lower in
      HCCs with intrahepatic metastasis (p<0.05). Cyclin D1 overexpression and aberrant
      p53 expression could be associated with the progression of HBV-related HCC, and
      might have a less crucial role in the DN-HCC sequence. In addition, elevated
      expression of p27 and p16 proteins might have inhibitory action to the
      intrahepatic metastasis of HBV-related HCC.

PMID- 11511788
TI  - Overexpression of promyelocytic leukemia protein and alteration of PML nuclear
      bodies in early stage of hepatocarcinogenesis.
AB  - Promyelocytic leukemia protein (PML) is a major component of PML nuclear bodies
      (PML NBs). Fusion of promyelocytic leukemia alpha gene (PML) with retinoic acid
      receptor gene with the t (15;17) translocation causes disassembly of PML NBs,
      leading to development of acute promyelocytic leukemia. In contrast, PML
      overexpression as well as different morphological changes of PML NBs were
      described in a few solid tumors. In this study, the expression of PML through the
      multistep hepatocarcinogenesis was analyzed in 95 cases of human hepatocellular
      carcinomas (HCCs) for comparison along with dysplastic nodules (DNs) and
      background liver cirrhosis (LC) or chronic hepatitis by immunohistochemistry and
      immunoblot. In addition, cases of HCCs were further evaluated according to their
      histologic grade and etiology. The amount of PML as well as the number and size
      of PML NBs increased gradually through the progression from LC, DNs to HCCs. The
      overexpression of PML in HCCs was much more closely associated with HBV infection
      than HCV infection or alcoholic liver disease. The PML expression, however, was
      not correlated with histologic grade of HCCs. These results suggest that PML is
      involved in the early stage of multistep hepatocarcinogenesis, and HBV infection
      may be associated with the overexpression of PML and the morphological alteration
      of PML NBs.

PMID- 11511789
TI  - Parenchymal and nonparenchymal cellular responses in human hepatic regeneration.
AB  - To characterize cellular responses during hepatic regeneration, we examined 13
      explant livers and 5 liver allografts by immunohistochemistry for cytokeratin 7,
      HepPar1, CD68, alpha-smooth muscle actin (alpha-SMA) and proliferating cell
      nuclear antigen as well as reticulin and Masson-trichrome staining. Within a week
      after liver damage, elongated CD68-positive cells were detected along the border
      of necrotic area. The number of alpha-SMA-positive cells was slightly increased
      along the sinusoids. Ductular proliferation or fibrosis was negligible. After one
      or two weeks, the size and number of CD68-positive cells were markedly increased.
      alpha-SMA-positive cells increased in number within lobules and portal tracts.
      Ductular proliferation occurred predominantly at the limiting plate or along the
      border of necrotic areas. After one month, necrotic parenchyma was replaced by
      many ductules, CD68-positive cells, alpha-SMA-positive cells. Nodules of
      regenerating hepatocytes and irregular fibrosis were diffusely present. Other
      nonparenchymal cells were not significantly changed. These observations indicate
      that chronological interaction between nonparenchymal and parenchymal cells occur
      during the course of human hepatic regeneration and suggest extensive porto
      periportal fibrosis more than a few months after the onset of fulminant hepatitis
      is a major indicator of chronic functional impairment necessitating liver
      transplantation.

PMID- 11511790
TI  - Does albumin preinfusion potentiate diuretic action of furosemide in patients
      with nephrotic syndrome?
AB  - The aim of this cross-over study was to investigate whether albumin infusion
      before furosemide administration could potentiate the diuretic action of
      furosemide. Seven patients with nephrotic syndrome were given the following
      infusions in random order on two separate days: 1) a sham solution followed by
      160 mg of furosemide, 2) 100 ml of 20% human albumin followed by 160 mg of
      furosemide. Urine and serum furosemide concentrations were measured by high
      performance liquid chromatography. The increment of urine volume was greater in
      albumin preinfusion than in furosemide alone. However, the increments of sodium
      and chloride excretions between furosemide alone and albumin preinfusion were not
      different. No significant differences in the pharmacokinetic parameters between
      the two treatments were observed: area under the concentration-time curve (AUC:
      12.7+/-2.2 vs 15.1+/-4.4 g/ml hr), total plasma clearance (253+/-41 vs 256+/-54
      ml/min), volume of distribution (341+/-34 vs 494+/-153 ml/kg), elimination half
      life (4.0+/-1.1 vs 4.6+/-0.8 hr), and urine furosemide excretion of the
      administered amount (16.5+/-7.3 vs 7.5+/-1.6%). In conclusion, these data show
      that albumin preinfusion potentiated diuresis, but not natriuresis, of furosemide
      without any change in the pharmacokinetics of the agent in patients with
      nephrotic syndrome.

PMID- 11511791
TI  - Immunohistochemical study of the expression of alpha-smooth muscle actin and the
      proliferation marker Ki-67 of glomerulonephritis.
AB  - The aim of this study was to determine the relationship of alpha-smooth muscle
      actin (ASMA) and the proliferation marker Ki-67 of glomerulonephritis (GN).
      Immunohistochemical stainings with the usual streptavidin-biotin peroxidase
      method were performed on 86 renal biopsies using monoclonal 1A4 and Ki-67. The
      results of the quantitative evaluation of ASMA and Ki-67 were analyzed for the
      correlation between positive value of ASMA and Ki-67 in different GN. ASMA
      expressions of glomeruli were highest in acute post-infectious GN [APGN; 16.9
      Fraction Volume (FV)%], followed by unclassified proliferative GN (UnGN; 12.5
      FV%), membranoproliferative GN (MPGN; 8.5 FV%), lupus nephritis (LupusN; 6.3
      FV%), IgA nephritis (IgAN; 5.6 FV%), and normal control (0.1 FV%). The Ki-67
      staining was considerably elevated in lupusN (4.3 Ki-67 positives/glomerulus),
      APGN (2.7), MPGN (2.5), UnGN (1.66), IgAN (0.5), compared with that in normal
      control group (0.1 Ki-67 positives/glomerulus). Ki-67 value in each category of
      glomerular diseases was significantly different from that in the control biopsies
      (p<0.004). The relationship between morphometric results of ASMA and Ki-67 was
      statistically significant regardless of the diagnosis. (rs=0.425, p=0.000, ASMA=
      0.1113+0.1665 Ki-67). In conclusion, the immunohistochemical assessment of ASMA
      and Ki-67 expression in GN might be a reliable indicator for the progression of
      GN. This study indicates that active cellular proliferation is associated with
      increased actin deposition in glomeruli.

PMID- 11511792
TI  - Altered renal expression of aquaporin-2 water channels in rats with experimental
      two-kidney, one clip hypertension.
AB  - The present study was aimed at examining the regulation of aquaporin (AQP)-2
      water channels in the kidney in two-kidney, one clip (2K1C) hypertension. Rats
      were made 2K1C hypertensive for 6 weeks, and their expression of AQP2 channel
      proteins was determined in the clipped and contralateral kidneys. To examine the
      upstream affecting AQP2 channels, adenylyl cyclase activity was also determined.
      Along with the hypertension, in the clipped kidney, the abundance of AQP2
      proteins was significantly decreased in the cortex, outer and inner medulla,
      while their trafficking remained unaltered. Concomitantly with the reversal of
      the blood pressure at 24 hours following removal of the clip, the AQP2 abundance
      also returned to the control level. The arginine vasopressin-evoked generation of
      cAMP was decreased in the clipped kidney, which again was reversed to the control
      level following removal of the clip. In contrast, the expression of AQP2 channels
      as well as the activity of adenylyl cyclase remained unaltered in the
      contralateral kidney. These results indicate an altered regulation of AQP2 water
      channels in the clipped kidney in 2K1C hypertension.

PMID- 11511793
TI  - Apoptosis of skeletal muscle on steroid-induced myopathy in rats.
AB  - Recently apoptotic cell death has been reported in differentiated skeletal
      muscle, where apoptosis was generally assumed not to occur. To investigate
      whether apoptosis may contribute to the steroid-induced myopathy, rats treated
      with triamcinolone acetonide (TA) for 9 days were sacrificed for detecting
      apoptosis by in situ end labeling (ISEL) and electron microscopy in the soleus
      muscles. Immunohistochemical stainings of Fas antigen and p53 protein were
      performed to examine whether apoptosis-related proteins were present in the
      myopathy. Muscle fiber necrosis and apoptotic myonuclei appeared in the soleus
      muscles following administration of TA, while control muscles showed no evidences
      for apoptosis. Fas antigen was not detected in control muscles, but expressed in
      the soleus muscles of steroid-induced myopathy. Some of the Fas antigen
      expressing muscle fibers were positive for ISEL. p53 protein was not detected in
      any muscle fibers. These findings indicate that TA can induce apoptosis in
      differentiated skeletal muscles, and Fas antigen might be partly related to
      apoptotic muscle death in steroid-induced myopathy.

PMID- 11511794
TI  - Sleep duration, subjective sleep disturbances and associated factors among
      university students in Korea.
AB  - Objective of this study was to look into sleep patterns of university students in
      association with their lifestyle, specifically to examine mean sleep duration,
      prevalence of sleep disturbances and their correlates. This study also aimed to
      examine a possible association of sleep patterns of young adults with new media
      like computers and videos, which were supposed to have a great influence on their
      lifestyle. Self-reported sleep data were derived from questionnaires administered
      to a total of 1,414 students of one university located in Chullabuk-do, Korea.
      Statistical methods such as t-test, analyses of variance, chi-square test and
      multivariate logistic regression were used for analysis. The mean sleep duration
      of the respondents was 6.7+/-1.3 hr. Of the respondents, 30.2% reported having
      insufficient sleep. About one third of them pointed to visual media including
      computers as the primary reason. The proportion of those having some types of
      sleep disturbances was 36.2%. The risk of subjective sleep disturbances was
      significantly lower among those perceiving themselves healthy than among those
      perceiving themselves unhealthy (OR=0.44; 95% CI: 0.34-0.57).

PMID- 11511795
TI  - p53 mutation and epidermal growth factor receptor overexpression in glioblastoma.
AB  - Recent molecular studies indicate two different genetic pathways leading to the
      development of glioblastoma; final progression of astrocytoma and de novo
      formation. To define the mutual relationships of cytogenetic changes in the
      pathogenesis of glioblastoma, molecular histopathologic alterations of p53 and
      epidermal growth factor receptor (EGFR) were evaluated by single stranded
      conformational polymorphion, reverse transcriptase-polymerase chain reaction and
      immunohistochemical stains in 15 primary and 21 secondary glioblastomas.
      Mutations in p53 gene and positive immunoreactivity to p53 protein (DO1) were
      more prevalent in secondary glioblastomas than in primary glioblastomas. A
      correlation between p53 mutations and p53 immunopositivities in glioblastomas was
      observed in 83.3% of the cases. All cases with positive p53 immunoreactivities
      showed p53 mutations; however, 13.9% of glioblastomas with p53 immuno
      positivities lacked the relevant mutations. EGFR amplifications were detected in
      73.3% of primary glioblastomas and 9.5% of secondary glioblastomas (p<0.001). The
      concurrence of p53 mutation and EGFR amplification was revealed in only 2 out of
      15 primary glioblastomas and none among the secondary glioblastomas.
      Immunoreactivities for EGFR were noted in 66.7% of primary glioblastomas and in
      9.5% of secondary glioblastomas (p<0.001). A correlation between EGFR
      amplification and EGFR immunopositivity in glioblastomas was observed in 91.7% of
      the cases. These data indicate that EGFR amplification and p53 mutations are two
      independent genetic events in the development of glioblastomas.

PMID- 11511796
TI  - Immunochemical characterization of brain and pineal tryptophan hydroxylase.
AB  - Recombinant mouse tryptophan hydroxylase (TPH) was expressed in Escherichia coli,
      using a bacterial expression vector and has been purified to homogeneity by
      sonication followed by Sepharose 4B column chromatography and native slab gel
      electrophoresis. This purified enzymatically active TPH protein was used for
      production of a specific antiserum. This antiserum identified the predicted TPH
      band (molecular weight, 54 kDa) on Western blot of crude extracts from the rat
      and mouse dorsal raphe, and the rat pineal gland. However, this antiserum
      recognized an additional protein band of lower molecular weight (48 kDa) in
      pineal extract. It is not clear whether the 48 kDa TPH band represents an isozyme
      or a protease cleavage product of TPH. Since the pineal gland contains higher TPH
      mRNA and lower TPH activity when it is compared with dorsal raphe nucleus enzyme,
      this lower molecular weight TPH may participate in the reduced TPH specific
      activity. In addition, there are no specific TPH inhibitors in the pineal gland
      and this lower molecular weight TPH is inactive or has a very low specific
      activity. This antiserum specifically immunostained serotonergic cell bodies in
      the dorsal raphe nuclei, some large caliber serotonergic processes in the dorsal
      raphe area as well as terminals in the olfactory bulb. It also immunolabeled the
      pineal gland and immunoprecipitated equally well TPH protein from the dorsal
      raphe nucleus and the pineal gland in a concentration-dependent manner.

PMID- 11511797
TI  - Synergistic effects between intrathecal clonidine and neostigmine in the formalin
      test.
AB  - Spinal alpha-2 adrenoceptors and cholinergic receptors are involved in the
      regulation of acute nociception and the facilitated processing. The aim of this
      study was to examine the pharmacological effect of an intrathecal alpha-2 agonist
      and a cholinesterase inhibitor on the facilitated pain model induced by formalin
      injection and to determine the nature of drug interaction using an isobolographic
      analysis. Both intrathecal clonidine and neostigmine dose-dependently suppressed
      the flinching during phase 1 and phase 2. Intrathecal pretreatment with atropine
      reversed the antinociceptive effects of clonidine and neostigmine in both phases.
      Pretreatment with intrathecal yohimbine attenuated the effect of clonidine. The
      antinociception of clonidine and neostigmine was not reversed by mecamylamine.
      Isobolographic analysis showed that intrathecal clonidine and neostigmine acted
      synergistically in both phase 1 and 2. Intrathecal pretreatment with atropine and
      yohimbine antagonized the effect of the mixture of clonidine and neostigmine in
      both phases, but no antagonism was observed with mecamylamine pretreatment. These
      data indicate that spinal clonidine and neostigmine are effective to counteract
      the facilitated state evoked formalin stimulus, and these two drugs interact in a
      synergistic fashion. In addition, the analgesic action of intrathecal clonidine
      is mediated by spinal muscarinic receptors as well as alpha-2 adrenoceptors.

PMID- 11511798
TI  - A case of disseminated Trichosporon beigelii infection in a patient with
      myelodysplastic syndrome after chemotherapy.
AB  - Trichosporonosis is a potentially life-threatening infection with Trichosporon
      beigelii, the causative agent of white piedra. The systemic infection by this
      fungus has been most frequently described in immunocompromised hosts with
      neutropenia. Here, we report the first patient with disseminated infection by T.
      beigelii in Korea, acquired during a period of severe neutropenia after chemo
      therapy for myelodysplastic syndrome. The patient recovered from the infection
      after an early-intensified treatment with amphotericin B and a rapid neutrophil
      recovery. The disseminated infection by T. beigelii is still rare, however, is an
      emerging fatal mycosis in immunocompromised patients with severe neutropenia.

PMID- 11511799
TI  - A case of successful primary coronary intervention for the total occlusion of
      left main stem with the aid of abciximab.
AB  - A 61-yr-old male patient presented with severe chest pain with cardiogenic shock
      due to an extensive anterolateral myocardial infarction. Two-dimensional
      echocardiogram showed severe left ventricular systolic dysfunction (ejection
      fraction=17%). Emergent coronary angiogram obtained immediately after placing
      temporary pacing electrode revealed total thrombotic occlusion in the left main
      stem. We performed direct coronary intervention using kissing balloon technique
      with the aid of Abciximab (ReoPro) infusion. Residual stenosis with thrombus
      remained even after high pressure balloon dilatations, therefore we placed two
      stents, one in the ostia of left anterior descending (LAD) and the other in left
      circumflex artery (LCX). Coronary angiogram after kissing stents showed improved
      LAD and LCX flows without residual stenosis. Chest pain resolved and blood
      pressure normalized after coronary intervention. The whole procedure time was 15
      min. Follow-up coronary angiogram taken one week later showed patent previous
      stented arteries, and echocardiography demonstrated 40% of left ventricular
      ejection fraction. The clinical course for one-year follow-up was uneventful.

PMID- 11511800
TI  - A case of cholestatic autoimmune hepatitis and acute liver failure: an unusual
      hepatic manifestation of mixed connective tissue disease and Sjogren's syndrome.
AB  - Although hepatomegaly is reported to occur occasionally in patients with mixed
      connective tissue disease (MCTD) or Sjogren's syndrome (SS), autoimmune liver
      diseases such as primary biliary cirrhosis, sclerosing cholangitis, and
      autoimmune hepatitis in association with MCTD or SS have rarely been described.
      We report a case of severe cholestatic autoimmune hepatitis presenting with acute
      liver failure in a 40-yr-old female patient suffering from MCTD and SS. The
      diagnosis of MCTD and SS was made at the age of 38. The patient presented severe
      jaundice and elevation of conjugated bilirubin. The patient denied alcohol and
      drug use and had no evidence of viral hepatitis. On the 8th day of her
      hospitalization, the patient developed grade III hepatic encephalopathy. She was
      diagnosed as autoimmune hepatitis presenting with acute liver failure based on
      clinical features, positive FANA and anti-smooth muscle antibodies, negative anti
      mitochondrial antibodies, high titers of serum globulin, liver biopsy findings,
      and a good response to corticosteroid therapy, The patient was managed with
      prednisolone and the clinical symptoms, liver function test results, and liver
      biopsy findings showed much improvement after steroid therapy.

PMID- 11511801
TI  - Mucocele-like tumor of the breast associated with ductal carcinoma in situ and
      mucinous carcinoma : a case report.
AB  - Mucocele-like tumor (MLT) of the breast is a rare neoplasm. Although this lesion
      was considered benign when first described, the concept of a pathologic continuum
      with mucinous carcinoma was evident in subsequent reports. Only a few cases of
      MLT have been reported in Korea. We describe a case of MLT associated with ductal
      carcinoma in situ and mucinous carcinoma in a 34-yr-old female. Histological
      examination showed multiple mucus-filled cysts of varying size. Extravasated
      mucin was present in the surrounding stroma. The lining of the cysts in most
      areas were of flat or cuboidal epithelium and devoid of cellular atypia. The
      lining epithelium showed proliferative change ranging from atypical ductal
      hyperplasia to ductal carcinoma in situ, micropapillary type. A microscopic focus
      of mucinous carcinoma within MLT was also noted. None of the lesions exhibited
      epithelial reactivity for p53 protein. The patient is alive and well without
      evidence of disease 54 months after initial treatment. This case supports the
      concept that MLT encompasses a spectrum of pathologic lesions including benign
      tumor, atypical ductal hyperplasia, ductal carcinoma in situ, and mucinous
      carcinoma.

PMID- 11511802
TI  - Carcinoma originating from aberrant breast tissue of the right upper anterior
      chest wall : a case report.
AB  - Aberrant breast tissue is usually found in proximity to the normal breast, that
      is, in the axillary, sternal or clavicular regions. Carcinoma occurs more
      frequently in the aberrant tissue of the axilla than the extra-axillary site
      though the overall incidence of tumors of aberrant breast tissue is low. To our
      knowledge, studies regarding the carcinoma of aberrant breast tissue of the extra
      axillary site have been reported rarely. Here we report a recent case of
      carcinoma originating from the extra-axillary aberrant breast tissue, presenting
      as a subcutaneous nodule on the right upper anterior chest wall. It is suggested
      that subcutaneous nodules of uncertain origin around the periphery of the breast
      should be suspected for breast carcinoma as a differential diagnosis and treated
      properly.

PMID- 11511803
TI  - MR findings of the spinal paraganglioma : report of three cases.
AB  - Extraadrenal paragangliomas involving the spine is less common and usually takes
      the form of intradural compression of the cauda equina. The authors report three
      cases of spinal paragangliomas resulting in extradural spinal cord compression
      and their MR findings. The MR imaging revealed a well-demarcated extradural mass
      with low to intermediate signal intensity on T1-weighted images and intermediate
      to high signal intensity on T2-weighted images compared to paravertebral muscles.
      After Gd-DTPA administration, heterogeneous and intense enhancement was found.
      Multiple punctate and serpiginous structures of signal void due to high-velocity
      flow were noted around and within the tumors on all sequences. In one case, the
      signal void structures were well corresponded with feeding arteries on
      angiography. These may be the characteristic findings of the extraadrenal
      paraganglioma involving the spine.

PMID- 11511804
TI  - Therapeutic embolization of the dural arteriovenous malformation involving the
      jugular bulb.
AB  - Pulsatile tinnitus is a rarely occurring symptom of vascular origin. Most
      frequently, the symptoms are due to an arteriovenous malformation, to a tumor of
      the jugular glomus or to a local arterial stenosis. A 39-yr-old Korean male
      suffering from pulsatile tinnitus of the left ear was diagnosed to have dural
      arteriovenous malformation of the jugular bulb. Magnetic resonance imaging and
      angiography revealed a high-velocity vascular lesion encroaching the internal
      jugular vein and sigmoid sinuses. Digital subtraction angiography demonstrated a
      dural arteriovenous malformation involving the jugular bulb. The arterial supply
      was from the neuromeningeal branch of the left ascending pharyngeal artery and
      inferior tympanic artery. Stenosis of the left jugular vein caused retrograde
      venous drainage through the contralateral transverse sinus. Superselective
      embolization of these feeding arteries was successfully performed using 25%
      mixture of N-butylcyanoacrylate and lipiodol. In postembolization period, his
      complaints of pulsatile tinnitus and buzzing noise behind his left ear
      disappeared.

PMID- 11511805
TI  - Secondary amenorrhea caused by hydrocephalus due to aqueductal stenosis : report
      of two cases.
AB  - Amenorrhea is rarely presented as a manifestation of endocrinological
      disturbances in patients of chronic hydrocephalus. We describe two cases of
      secondary amenorrhea caused by hydrocephalus due to aqueductal stenosis. Two
      female patients of age 30 and 20 yr presented with amenorrhea and increasing
      headache. Magnetic resonance images revealed marked, noncommunicating
      hydrocephalus without any tumorous lesion. In one patient, emergent
      extraventricular drainage was necessary because of progressive neurological
      deterioration. Each patient underwent surgical intervention for the hydrocephalus
      ventriculoperitoneal shunt and endoscopic third ventriculostomy. Both resumed
      normal menstruation continuing so far with further normal menstrual bleeding.
      These two cases and others reported in the literature indicated that the surgical
      intervention for hydrocephalus resolves amenorrhea in all the cases of amenorrhea
      due to hydrocephalus. The suspected role of the surgery is the correction of
      increased intracranial pressure, which is an important pathogenetic factor in the
      development of amenorrhea.

PMID- 11511806
TI  - Obituary-Lars Svennerholm.

PMID- 11511807
TI  - Chemoenzymatic preparation of dermatan sulfate oligosaccharides as arylsulfatase
      B and alpha-L-iduronidase substrates.
AB  - Dermatan sulfate was partially depolymerized with chondroitin ABC lyase to obtain
      an oligosaccharide mixture from which an unsaturated disulfated tetrasaccharide
      was purified and characterized using nuclear magnetic resonance spectroscopy and
      electrospray ionization mass spectrometry. Chemical removal of the unsaturated
      uronate residue with mercuric acetate, followed by de-4-O-sulfation with
      arylsulfatase B (N-acetylgalactosamine 4-sulfatase) and N- acetylhexosaminidase
      catalyzed removal of the 2-acetamido-2-deoxy-D-galactospyranosyl residue at the
      non-reducing end afforded a monosulfated disaccharide of the structure alpha-L
      idopyranosyluronic acid (1-->3)-alpha,beta-D-2-acetamido-2-deoxy-4-O-sulfo
      galactopyranose. This monosulfated disaccharide serves as a substrate for
      mammalian alpha-L-iduronidase as demonstrated using fluorophore assisted
      carbohydrate electrophoresis.

PMID- 11511808
TI  - Glycosylations versus conformational preferences of cancer associated mucin core.
AB  - Synthetic oligosaccharide vaccines based on core STn (sialyl alpha2-6 GalNAc)
      carbohydrate epitopes are being evaluated by a number of biopharmaceutical firms
      as potential immunotherapeutics in the treatment of mucin-expressing
      adenocarcinomas. The STn carbohydrate epitopes exist as discontinuous clusters, O
      linked to proximal serine and threonine residues within the mucin sequence. In an
      effort to probe the structure and dynamics of STn carbohydrate clusters as they
      may exist on the cancer-associated mucin, we have used NMR spectroscopy and MD
      simulations to study the effect of O-glycosylation of adjacent serine residues in
      a repeating (Ser)n sequence. Three model peptides/glyco-peptides were studied: a
      serine trimer containing no carbohydrate groups ((Ser)3 trimer); a serine trimer
      containing three Tn (GalNAc) carbohydrates alpha-linked to the hydroxyls of
      adjacent serine sidechains ((Ser.Tn)3 trimer); and a serine trimer containing
      three STn carbohydrates alpha-linked to the hydroxyls of adjacent serine
      sidechains ((Ser.STn)3 trimer). Our results demonstrate that clustering of
      carbohydrates shifts the conformational equilibrium of the underlying peptide
      backbone into a more extended and rigid state, an arrangement that could function
      to optimally present the clustered carbohydrate antigen to the immune system.
      Steric effects appear to drive these changes since an increase in the size of the
      attached carbohydrate (STn versus Tn) is accompanied by a stronger shift in the
      equilibrium toward the extended state. In addition, NMR evidence points to the
      formation of hydrogen bonds between the peptide backbone NH protons and the
      proximal GalNAc groups in the (Ser.Tn)3 and (Ser.STn)3 trimers. The putative
      peptide-sugar hydrogen bonds may also play a role in influencing the conformation
      of the underlying peptide backbone, as well as the orientation of the O-linked
      carbohydrate. The significance of these results will be discussed within the
      framework of developing clustered STn-based vaccines, capable of targeting the
      clustered STn epitopes on the cancer-associated mucin.

PMID- 11511810
TI  - Glycosylation of the N-terminal potential N-glycosylation sites in the human
      alpha1,3-fucosyltransferase V and -VI (hFucTV and -VI).
AB  - Human alpha1,3-fucosyltransferase V and -VI (hFucTV and -VI) each contain four
      potential N-glycosylation sites (hFucTV: Asn60, Asn105, Asn167 and Asn198 and
      hFucTVI: Asn46, Asn91, Asn153 and Asn184). Glycosylation of the two N-terminal
      potential N-glycosylation sites (hFucTV: Asn60, Asn105 and hFucTVI: Asn46 and
      Asn91) have never been studied in detail. In the present study, we have analysed
      the glycosylation of these potential N-glycosylation sites. Initially, we
      compared the molecular mass of hFucTV and -VI expressed in COS-7 cells treated
      with tunicamycin with the mass of the proteins in untreated cells. The difference
      in molecular mass between the proteins in treated and untreated cells
      corresponded to the presence of at least three N-linked glycans. We then made a
      series of mutants, in which the asparagine residues in the N-terminal potential N
      glycosylation sites were replaced by glutamine. Western blotting analyses
      demonstrated that both sites in hFucTV were glycosylated, whereas in hFucTVI only
      one of the sites (Asn91) was glycosylated. All the single mutants and the hFucTVI
      N46Q/N91Q double mutant exhibited enzyme activities that did not differ
      considerably from the wt activities. However, the enzyme activity of the hFucTV
      N60Q/N105Q double mutant was reduced to approximately 40% of the wt activity. In
      addition, castanospermine treatment diminished the enzyme activity and hence
      trimming of the N-linked glycans are required for expression of full enzyme
      activity of both hFucTV and -VI. The present study demonstrates that both of the
      N-terminal potential N-glycosylation sites in hFucTV and one of the sites in
      hFucTVI are glycosylated. Individually, their glycosylation does not contribute
      considerably to expression of enzyme activity. However, elimination of both sites
      in hFucTV reduces the enzyme activity.

PMID- 11511809
TI  - Characterisation of the enzymatic 4-O-acetylation of sialic acids in microsomes
      from equine submandibular glands.
AB  - Microsomes prepared from equine submandibular glands and incubated with tritium
      labelled AcCoA incorporated acid-insoluble radioactivity in a manner dependent on
      time, protein, membrane integrity and AcCoA concentration, with incorporation
      being optimal at 37 degrees C and pH 6.6. Under the experimental conditions used
      a K(M) of 32.1 microM for AcCoA and a V(max) of 1.2 pmol/mg protein x min was
      obtained. The incorporation of acid-insoluble radioactivity was also inhibited by
      CoA in a competitive manner (K(i)=240 microM), as well as by para
      chloromercuribenzoate, 3'-dephospho-CoA, 5'-IDP, 5'-ADP, beta-NAD and 4,4'
      diisothiocyanatostilbene-2,2'-disulfonate. We demonstrate here that this
      incorporation of radioactivity into endogenous sialic acid is due to the action
      of an AcCoA:sialate-4-O-acetyltransferase [EC 2.3.1.44]. Radio thin-layer
      chromatography analyses of propionic acid-released sialic acids showed that the
      incorporation of radioactivity correlated with the formation of a radiolabelled
      species that co-migrated with authentic Neu4,5Ac2. Saponification experiments
      using NaOH, mouse hepatitis virus strain S and Influenza C/JJ/50 virus also
      showed that the transfer of [3H]acetyl groups from [3H]AcCoA to endogenous sialic
      acid acceptors was occurring exclusively at carbon 4 of the pyranose ring.

PMID- 11511811
TI  - Molecular cloning and expression analysis of a mouse UDP-GlcNAc:Gal(beta1
      4)Glc(NAc)-R beta1,3-N-acetylglucosaminyltransferase homologous to Drosophila
      melanogaster Brainiac and the beta1,3-galactosyltransferase family.
AB  - We have isolated a murine cDNA coding for a beta1,3-N
      acetylglucosaminyltransferase enzyme ( beta3GnT). This enzyme is similar in
      sequence to Drosophila melanogaster Brainiac and to the murine and human beta1,3
      galactosyltransferase family of proteins. The mouse beta 3GnT protein is 397
      amino acids in length and contains 7 cysteine residues that are conserved in the
      human orthologue. beta 3GnT is a type II membrane protein localized to the Golgi
      apparatus. Enzyme assays with recombinant mouse beta 3GnT reveal that it has a
      preference for acceptors with Gal(beta1-4)Glc(NAc) at the non-reducing termini.
      Proton NMR analysis of product showed incorporation of GlcNAc in beta1,3 linkage
      to the terminal Gal of Gal(beta1-4)Glc(beta1-O-benzyl). Northern blot analysis
      revealed the presence of a single 3.0[emsp4 ]kb transcript in all adult mouse and
      human organs tested, with highest levels in the kidney, liver, heart and
      placenta. The beta 3GnT gene is also expressed in a number of tumor cell lines.
      The human orthologue of beta 3GnT is located on chromosome 2pl5.

PMID- 11511812
TI  - The N-glycan acceptor specificity of a glucuronyltransferase, GlcAT-P, associated
      with biosynthesis of the HNK-1 epitope.
AB  - The acceptor specificity of a rat brain glucuronyltransferase, GlcAT-P,
      associated with biosynthesis of the HNK-1 epitope on glycoproteins, was
      investigated using asialoorosomucoid as a model acceptor substrate. Structural
      analysis of N-linked oligosaccharides, to which glucuronic acid was transferred
      by GlcAT-P, by means of two-dimensional mapping of pyridylamino-oligosaccharides
      and MS spectrometry, demonstrated that the enzyme transferred glucuronic acid to
      bi-, tri-, and tetra-antennary complex type sugar chains, with almost equal
      efficiency, indicating that the enzyme has no preference as to the number of
      acceptor sugar branches. Next, we studied the branch specificity of this enzyme
      by means of the selective branch scission method involving two step
      exoglycosidase digestion using authentic pyridylamino-oligosaccharides. The GlcAT
      P is highly specific for the terminal N-acetyllactosamine structure and no
      glucuronic acid was incorporated into a Galbeta1-3GlcNAc moiety. The GlcAT-P
      transferred glucuronic acid to the galactose residues in the N-acetyllactosamine
      branches of bi-, tri-, and tetra-antennary oligosaccharide chains, with different
      efficiencies and most preferentially to those in the Galbeta1-4GlcNAcbeta1
      4Manalpha1-3 branch.

PMID- 11511813
TI  - Role of linkage specific 9-O-acetylated sialoglycoconjugates in activation of the
      alternate complement pathway in mammalian erythrocytes.
AB  - Substitution of the -OH group at C-9 of sialic acid by an O-acetyl ester has been
      suggested to modify various biological phenomena that are regulated by sialic
      acids. Amongst them, enhancement of erythrocyte lysis by 9-O-acetylated sialic
      acid determinants through modulation of the alternate pathway of complement has
      been extensively studied on murine erythrocytes [1]. A variable expression of
      linkage specific 9-O-acetylated sialoglycoconjugates as defined by the
      lectinogenic epitope of Achatinin-H namely 9-O-acetylated sialic acid alpha2-
      >6Gal NAc was identified on rabbit, guinea pig, hamster, rat, mouse and human
      erythrocytes. This differential expression of linkage specific 9-O-acetylated
      sialoglycoconjugates strongly correlated with the susceptibility of mammalian
      erythrocytes to lysis by the alternate pathway of complement. Additionally, low
      levels of antibodies directed against O-acetylated sialic acids in these
      mammalian species suggested that these constitutively present determinants have
      low immunogenicity. Taken together, our results indicate that complement mediated
      hemolysis depends not simply upon the extent of surface 9-O-acetylated sialic
      acids present but more importantly upon the specific linkage.

PMID- 11511814
TI  - Genetic engineering of CHO cells producing human interferon-gamma by transfection
      of sialyltransferases.
AB  - Natural human interferon-gamma (hIFN-gamma) contains mainly biantennary complex
      type sugar chains. We previously remodeled the branch structures of N-glycans on
      hIFN-gamma in Chinese hamster ovary (CHO) cells by overexpressing UDP-N
      acetylglucosamine: alpha1,6-D-mannoside beta1,6-N-acetylglucosaminyltransferase
      (GnT-V). Normal CHO cells primarily produced hIFN-gamma having biantennary sugar
      chains, whereas a CHO clone, designated IM4/Vh, transfected with GnT-V, primarily
      produced hIFN-gamma having GlcNAcbeta1-6 branched triantennary sugar chains when
      sialylation was incomplete and an increase in poly-N-acetyllactosamine (Galbeta1
      4GlcNAcbeta1-3)n was observed. In the present study, we introduced mouse Galbeta1
      3/4GlcNAc-R alpha2,3-sialyltransferase (ST3Gal IV) and/or rat Galbeta1-4GlcNAc-R
      alpha2,6-sialyltransferase (ST6Gal I) cDNAs into the IM4/Vh cells to increase the
      extent of sialylation and to examine the effect of sialyltransferase (ST) type on
      the linkage of sialic acid. Furthermore, we speculated that sialylation extent
      might affect the level of poly-N-acetyllactosamine. We isolated four clones
      expressing different levels of alpha2,3-ST and/or alpha2,6-ST. The extent of
      sialylation of hIFN-gamma from the IM4/Vh clone was 61.2%, which increased to
      about 80% in every ST transfectant. The increase occurred regardless of the type
      of overexpressed ST, and the proportion of alpha2,3- and alpha2,6-sialic acid
      corresponded to the activity ratio of alpha2,3-ST to alpha2,6-ST. Furthermore,
      the proportion of N-glycans containing poly-N-acetyllactosamine was significantly
      reduced (less than 10%) in the ST transfectants compared with the parental IM4/Vh
      clone (22.9%). These results indicated that genetic engineering of STs is highly
      effective for regulating the terminal structures of sugar chains on recombinant
      proteins in CHO cells.

PMID- 11511817
TI  - Dendritic cells transduced with HIV Nef express normal levels of HLA-A and HLA-B
      class I molecules.
AB  - HIV Nef protein is important for viral pathogenesis and disease progression. Nef
      downregulates CD4 and major histocompatibility antigens on the surface of HIV
      infected T cells. HIV also infects dendritic cells. We wanted to determine if Nef
      had a similar function in professional antigen-presenting cells, where
      downregulation of Class I could have important effects on the initiation of HIV
      specific cytolytic T cell responses. We infected human dendritic cells with
      adenovirus expressing Nef. In contrast to T cells and Hela cells, HLA-A and HLA-B
      molecules are not downregulated nor are other class I molecules increased. We
      show that, in dendritic cells, HIV Nef has little effect on CD4 or Class I
      expression.

PMID- 11511818
TI  - Risk factors for severe hepatic injury after introduction of highly active
      antiretroviral therapy.
AB  - OBJECTIVES: Treatment of HIV infection with highly antiretroviral therapy (HAART)
      may be limited by liver toxicity. Its incidence and risk factors are not well
      known. PATIENTS AND METHODS: Retrospective chart review. Naive patients beginning
      HAART between January 1997 and January 2000. Severe transaminase elevation was
      defined as fivefold or higher rise over upper normal limits, or as > or =3.5-fold
      rise above abnormal baseline values. RESULTS: Of 222 study subjects, 38%, 5%, and
      2% were coinfected with hepatitis C virus (HCV), hepatitis B virus, and hepatitis
      D virus, respectively. Besides two nucleoside reverse transcriptase inhibitors
      (NRTIs), 96 patients received protease inhibitors (PIs), 90 received
      nonnucleoside reverse transcriptase inhibitors (NNRTIs), and 35 received a PI +
      NNRTI combination. Severe hepatic injury developed in 21 (9%): 10% PI, 9%, and 9%
      PI + NNRTI. Both univariate and multivariate analyses identified alcohol abuse,
      HCV coinfection, and older age as independent risk factors. Predictor variables
      in the final multivariate model were: alcohol abuse (risk ratio [RR], 5.87; 95%
      confidence interval [CI], 1.49-23.15; p =.01], positive HCV serology (RR, 3.99;
      95% CI, 1.32-12.10; p =.01], and older age (RR, 1.11; 95% CI, 1.04-1.18; p =
      0.001). CONCLUSIONS: Nearly 10% of study subjects who start HAART experience
      severe transaminase elevation, irrespective of the treatment. Avoidance of
      alcohol abuse, especially in study subjects coinfected with HCV, will reduce the
      risk of hepatic injury after HAART. When possible, prior treatment for chronic
      HCV infection should be considered.

PMID- 11511819
TI  - Evolution of cervical abnormalities among women with HIV-1: evidence from
      surveillance cytology in the women's interagency HIV study.
AB  - OBJECTIVE: To determine incidence, progression, and regression rates for abnormal
      cervical cytology and their correlates among women with HIV. METHODS: In a
      multicenter prospective cohort study conducted October 1, 1994, through September
      30, 1999 at university, public, and private medical centers and clinics, 1639 HIV
      seropositive and 452 seronegative women were evaluated every 6 months for up to 5
      years using history, cervical cytology, T-cell subsets, and quantitative plasma
      HIV RNA. Human papillomavirus (HPV) typing at baseline was determined by
      polymerase chain reaction. Cytology was read using the Bethesda system, with any
      smear showing at least atypia considered abnormal. Poisson regression identified
      factors associated with incident cytologic abnormalities whereas logistic
      regression identified those associated with progression and regression after an
      abnormality. RESULTS: At least one abnormal smear was found during all of follow
      up among 73.0% of HIV-seropositive patients and 42.3% of seronegatives (p <.001).
      Only 5.9% of seropositives ever developed high-grade lesions, and the proportion
      with high-grade findings did not rise over time. Incidence of atypical squamous
      cells of uncertain significance (ASCUS) or more severe lesions among HIV
      seropositive patients and seronegative patients was 26.4 and 11.0/100 woman-years
      (rate ratio [RR], 2.4; 95% confidence interval [CI], 1.9-3.0), whereas that of at
      least low-grade squamous intraepithelial lesions (SIL) was 8.9 and 2.2/100 (RR,
      4.0; CI, 2.6-6.1). HIV status, detection of the presence of human papillomavirus
      (HPV), CD4 lymphocyte count, and HIV RNA level predicted incidence of abnormal
      cytology (p <.05); HPV detection and HIV RNA level predicted progression (p
      <.01); and HPV detection, CD4 lymphocyte count, and HIV RNA level predicted
      regression (p <.001). Rates of incidence, progression, and regression of abnormal
      cytology did not differ between HIV seronegative women and seropositive women
      with CD4 lymphocyte counts >200/mm(3) and HIV RNA levels <4000/ml of similar HPV
      status. CONCLUSIONS: Although HIV infected women were at high risk for abnormal
      cytology, high-grade changes were uncommon. HIV status, HPV detection, CD4
      lymphocyte count, and HIV RNA level predicted the incidence of cervical cytologic
      abnormalities. Progression was significantly increased only among the most
      immunosuppressed women, while regression was significantly reduced in all HIV
      seropositive women except those with the best controlled HIV disease.

PMID- 11511820
TI  - Lipodystrophic syndromes and hyperlipidemia in a cohort of HIV-1-infected
      patients receiving triple combination antiretroviral therapy with a protease
      inhibitor.
AB  - OBJECTIVES: To assess the frequency and features of lipodystrophic syndromes in
      HIV-1-infected patients receiving highly active antiretroviral therapy (HAART)
      with a protease inhibitor (PI), and examine whether clinical and biologic
      abnormalities are always associated in these conditions. METHODS: Retrospective
      prospective single-center observational study of 175 patients. Comparisons for
      continuous variables by t-test and paired t-test, and Kaplan-Meier analysis of
      time to onset of lipodystrophy were performed. RESULTS: In all, 51 patients (29%)
      had morphologic changes, after a mean HAART duration of 20.0 +/- 6.1 months, and
      were categorized into pure lipoatrophy (n = 16), mixed syndrome (truncal fat
      accumulation and face or limb lipoatrophy) (n = 30) or pure truncal fat
      accumulation (n = 5). Because of the small number, the latter group was not
      analyzed statistically. No differences were found among patients with
      lipoatrophy, mixed syndrome, or no lipodystrophy, in terms of gender, CD4 count,
      and HIV RNA plasma load at time of HAART initiation, nor in response to
      treatment. Patients with a mixed syndrome were older. Patients with lipoatrophy
      had longer duration of HIV disease, pre-HAART exposure to nucleoside analog
      therapy, and HAART. Baseline and pre-HAART fasting triglyceride levels were
      higher in patients who developed lipoatrophy, whereas weight and fasting
      cholesterol were higher in patients who developed a mixed syndrome. After 12 and
      24 months on HAART, triglycerides and cholesterol rose significantly in all
      patients, independently of lipodystrophy, whereas these parameters were not
      increased during nucleoside analog therapy. CONCLUSIONS: Nucleoside analog
      exposure appears as a risk factor for lipoatrophy. Age and nutritional status
      (reflected by baseline weight, triglycerides and cholesterol) may influence the
      evolution to lipoatrophy or a mixed syndrome. Hyperlipidemia is observed in the
      absence of lipodystrophy and depends on PI exposure.

PMID- 11511821
TI  - Adefovir and tenofovir susceptibilities of HIV-1 after 24 to 48 weeks of adefovir
      dipivoxil therapy: genotypic and phenotypic analyses of study GS-96-408.
AB  - OBJECTIVE: To determine whether genotypic changes in HIV-1 (HIV) reverse
      transcriptase (RT) occur during adefovir dipivoxil (ADV) therapy that may alter
      the susceptibility of HIV to adefovir or the related nucleotide inhibitor,
      tenofovir. DESIGN AND METHODS: GS-96-408 was a 1:1 randomized, double-blind,
      phase III clinical trial assessing the safety and efficacy of 120-mg daily ADV
      compared with placebo for the treatment of HIV when added to stable background
      antiretroviral therapy (ART). Of 442 patients enrolled, 142 were prospectively
      selected for a virology substudy. Baseline and posttreatment (weeks 24-48) plasma
      samples were genotypically analyzed in HIV RT. HIV from ADV-treated patients who
      developed RT mutations at week 24 were also phenotypically analyzed. RESULTS:
      Nucleoside-associated RT mutations arose with similar frequency among the ADV-and
      placebo-treated patients, 32% (n = 23) and 28% (n = 20), respectively, during the
      24-week blinded treatment phase. RT mutations previously selected by adefovir in
      vitro (K70E or K65R) did not develop in any patient. Most mutations were typical
      zidovudine (ZDV)-resistance mutations (e.g., M41L, D67N, K70R, T215Y) in patients
      taking ZDV or stavudine (d4T) concomitantly, demonstrating directly in the
      placebo arm that d4T is able to select for these mutations. There appeared to be
      more patients developing D67N and K70R mutations in the ADV arm versus more T215Y
      mutations in the placebo arm. Between weeks 24 and 48, 19 of 50 patients (38%) in
      the ADV arm developed similar RT mutations. The mean HIV RNA responses at weeks
      24 and 48 among the ADV-treated patients developing RT mutations were -0.68
      log(10) copies/ml (n = 23) and -0.52 log(10) copies/ml (n = 19), respectively,
      similar to the overall week-24 and week-48 responses (-0.53 and 0.48 log(10)
      copies/ml, respectively). Patient-derived HIV expressing the observed RT
      mutations showed insignificant decreases in adefovir susceptibility compared with
      wild-type in 12 of 16 cases (< threefold). HIV from 1 patient showed
      significantly reduced susceptibility to tenofovir, which was in association with
      a double insertion mutation after codon 69 that was also present at baseline.
      CONCLUSIONS: HIV RT changes that arose during ADV therapy appear attributable to
      the patient's background ART. ADV therapy may have influenced the pattern of ZDV
      associated resistance mutations that developed, but this did not result in an
      observed loss of viral load suppression. There was a trend toward decreased
      phenotypic susceptibility to adefovir in ADV-treated patients, with 4 of 16
      analyzed patients showing mild, but significantly decreased susceptibility
      associated with the additional ZDV-associated mutations. Decreased susceptibility
      to the related nucleotide analog, tenofovir, was not observed to develop in ADV
      treated patients.

PMID- 11511822
TI  - Efavirenz as a substitute for protease inhibitors in HIV-1-infected patients with
      undetectable plasma viral load on HAART: a median follow-up of 64 weeks.
AB  - We investigated, in a prospective cohort follow-up study, whether substituting
      efavirenz (EFV) for protease inhibitors (PIs) could be safe in HIV-infected
      patients with optimal viral suppression achieved on PI-containing regimens. In
      patients with undetectable plasma viral load (pVL) <50 copies/ml who were naive
      to therapy with nonnucleoside reverse transcriptase inhibitors (NNRTIs), PIs were
      replaced by EFV whereas associated nucleoside analogs (NAs) were retained. 62
      patients were enrolled. Median follow-up on EFV was 64 weeks (2-88 weeks). Side
      effects due to EFV occurred in 48 patients. Two patients experienced a high level
      viral rebound due to diminished compliance; 55 (88.7%) maintained a pVL <50
      copies/ml; 3 showed one episode of viremia (52-89 copies/ml); 2 stopped EFV
      before any VL control. Mean CD4 cell count did not change significantly. One AIDS
      patient experienced a single cutaneous recurrence of Kaposi's sarcoma after 40
      weeks on EFV. Replacing PI with EFV in patients with optimal pVL suppression
      appears to be safe both virologically and immunologically.

PMID- 11511823
TI  - Screening for cervical cancer in HIV-infected women receiving care in the United
      States.
AB  - OBJECTIVE: We examined the sociodemographic, clinical and provider factors
      associated with screening for cervical cancer among HIV-infected women. METHODS:
      We studied a national sample representing 43,490 women receiving treatment of HIV
      infection who completed first follow-up surveys of the HIV Cost and Service
      Utilization Study (HCSUS). All women were asked, "In the past 12 months, have you
      had a Pap test?" Women reporting an abnormal Pap test result were asked whether
      they had been told antibiotics could cure abnormal cells, and whether they were
      scheduled for another Pap test or for a colposcopy within 3 months. RESULTS: Of
      the population represented, 81% had had a Pap test in the past 12 months. Women
      who reported having a gynecologist and primary care physician at the same
      clinical site were almost twice as likely (odds ratio, 1.9; 95% confidence
      interval, 1.3-3.0) as other women to report Pap testing. Among women who reported
      abnormal Pap test results and were not told antibiotics could cure abnormal
      cells, 95% were scheduled for a repeat Pap test or colposcopy, but 15% of the
      women had not received their repeat Pap test or colposcopy. CONCLUSION: Although
      Pap test rates and appropriate referral for abnormal findings were high among HIV
      tested women, many women with initially abnormal Pap test results did not
      actually receive follow-up Pap testing or colposcopy. Providing gynecologic care
      at the same site as primary HIV care would likely improve delivery of needed
      gynecologic care for women.

PMID- 11511824
TI  - Undiagnosed and unreported AIDS deaths: results from the San Francisco Medical
      Examiner.
AB  - To determine whether AIDS surveillance misses a substantial number of persons who
      die with unreported AIDS, we conducted a cross-sectional survey of decedents
      examined by the San Francisco (SF) Medical Examiner. Decedents who received
      toxicology screening were tested for HIV antibody and examined for evidence of
      AIDS. Names of decedents with positive or indeterminate HIV antibody test results
      were cross-referenced against the SF AIDS registry to identify previously
      reported AIDS cases. Medical records of unreported cases were reviewed to
      determine whether AIDS had been diagnosed prior to death. Of 1959 decedents
      tested, 176 (9%) were HIV positive; 105 (60%) were identified as having AIDS by
      the Medical Examiner. Of the 105 AIDS cases, 101 (96%) had been previously
      diagnosed; 98 (97%) had been previously reported. Overall, diagnosis and
      reporting were 93% complete. HIV-infected decedents were more likely than those
      uninfected to be men and <45 years old, and less likely to be Asian/Pacific
      Islander or Native American (p <.001). They were more likely to have died of
      suicide (p <.05) or drug abuse/overdose (p <.001). In SF, AIDS case reporting is
      highly complete. Current surveillance activities, which identify cases from
      health care settings, are appropriate. To decrease deaths among HIV-infected
      persons, suicide prevention and substance abuse treatment programs are needed.

PMID- 11511825
TI  - Homozygous and heterozygous CCR5-Delta32 genotypes are associated with resistance
      to HIV infection.
AB  - OBJECTIVE: To investigate evidence for resistance to HIV-1 infection associated
      with the heterozygous genotype CCR5-+/Delta32 and with the homozygous genotype
      CCR5-Delta32/Delta32, which results in a nonfunctional CCR5 receptor. DESIGN:
      Cohort study of initially HIV-seronegative high-risk individuals from eight
      different cities. Enrollment data were analyzed to investigate the association of
      demographic factors and risk behaviors with CCR5 genotypes on the assumption that
      increased genotype prevalence among persons with histories of longer or more
      intensive exposure to HIV would indicate HIV resistance associated with that
      genotype. Longitudinal data were analyzed to investigate the association of HIV
      seroincidence with CCR5 genotypes. The cohort of 2996 individuals included 1892
      men who have sex with men (MSM), 474 male injection drug users (IDUs), 347 women
      at heterosexual risk, and 283 female IDUs. MEASUREMENTS: CCR5 genotype, HIV
      serostatus, demographic factors, and risk behaviors during the 6 months before
      enrollment, followed by measurement of HIV seroincidence during the subsequent 18
      months (for men) and 24 months (for women). RESULTS: Forty (1.3%) subjects were
      homozygous CCR5-Delta32/Delta32 and 387 (12.9%) were heterozygous CCR5-+/Delta32.
      All but 1 CCR5-Delta32/Delta32 individuals and 51 CCR5-+/Delta32 individuals were
      Caucasian. Among 1531 Caucasian MSM, CCR5-+/Delta32 individuals were present more
      frequently (22.3%) among those reporting unprotected receptive anal intercourse
      than among those not reporting this risk (15.9%) (p =.002), suggesting a
      selective advantage of the heterozygous genotype. CCR5-+/Delta32 individuals also
      had a significantly reduced relative risk of HIV seroconversion adjusted for
      unprotected receptive anal intercourse compared with CCR5-/+ individuals
      (relative risk = 0.30, 95% confidence interval [CI]: 0.08-0.97). CCR5
      Delta32/Delta32 prevalence among Caucasian MSM was significantly associated with
      age among subjects recruited from high HIV seroprevalence cities (New York City
      and San Francisco) (odds ratio [OR] for each decade increase in age = 2.57, CI:
      1.56-4.21) but not among those recruited from lower HIV prevalence sites (Boston,
      Chicago, Philadelphia, Seattle, and Providence/Pawtucket, Rhode Island) (OR =
      1.20, CI: 0.75-1.89). CONCLUSIONS: Cross-sectional and longitudinal analyses
      indicated that among high-risk HIV seronegative MSM, CCR5-+/Delta32 and CCR5
      Delta32/Delta32 are associated with protection against HIV infection. These
      findings imply that strategies aimed at reducing susceptibility to HIV infection
      by blocking CCR5 receptor sites need not seek blockage of all receptor sites to
      achieve an imperfect but substantial degree of protection.

PMID- 11511826
TI  - Cost-effectiveness of the Mpowerment Project, a community-level intervention for
      young gay men.
AB  - OBJECTIVES: Previous evaluation demonstrated that the Mpowerment Project
      community-level intervention for young gay men reduces HIV risk behaviors. The
      current analysis was undertaken to estimate the intervention's health and
      economic outcomes. DESIGN/METHODS: We conducted a retrospective cost
      effectiveness analysis. We estimated HIV infections averted, the gain in quality
      adjusted life years (QALYs), cost per infection averted, and net cost. Using a
      population-level model, we portrayed two epidemic scenarios: the first with
      stable HIV prevalence and the other with rising HIV prevalence. Inputs included
      behavior change resulting from the intervention and program cost data. Cost was
      calculated from three perspectives: societal; societal excluding volunteer time;
      and that of a community-based organization (CBO). Outcomes were calculated for 1,
      5 (baseline), and 20 years. RESULTS: The Mpowerment Project averted an estimated
      2.0 to 2.3 HIV infections in the first year (according to the epidemic scenario),
      5.0 to 6.2 over 5 years, and 9.2 to 13.1 over 20 years. The societal cost per HIV
      infection averted was estimated at between $14,600 and $18,300 over 5 years.
      Costs per infection averted were 28% lower when excluding volunteer time and 35%
      lower from the CBO perspective. Net savings were $700,000 to $900,000 over 5
      years from the societal perspective. CONCLUSIONS: The Mpowerment Project is cost
      effective compared with many other HIV prevention strategies. The cost per HIV
      infection prevented is far less than the lifetime medical costs of HIV disease.

PMID- 11511827
TI  - HIV incidence estimates among women of childbearing age in the area around Paris,
      France: no evidence for any effect of age or time.
AB  - OBJECTIVE: To explore whether there are any age or time effects on the HIV
      incidence rate among women of childbearing age in the area around Paris (France).
      DESIGN: Three seroprevalence surveys were conducted among pregnant women in the
      Paris area (PREVAGEST) during three periods (1990-1991, 1992-1993, 1994-1995);
      their data were used to derive HIV incidence estimates with Ades and Medley's
      method. To assess the power of our study, data were also simulated with a
      demographic model under different assumptions for HIV-incidence rates. RESULTS:
      No age or time effect was detected on HIV incidence in the Paris area during the
      period from 1990 to 1995. Analysis of simulated surveys showed that with the
      sample size of the PREVAGEST surveys, the method was able to detect an age or
      time effect with a relative risk of about 2.5 between age groups or periods.
      CONCLUSION: We conclude that the method is applicable to our data. If any
      existed, age or time effect was quite likely no higher than 2.5. As we previously
      reported using another method, incidence of HIV infection among women of
      childbearing age in the Paris area can be estimated at 0.74/1,000 per year (95%
      confidence interval, 0.62-0.87) from 1990 through 1995.

PMID- 11511828
TI  - Increasing prevalence of non-clade B HIV-1 strains in heterosexual men and women,
      as monitored by analysis of reverse transcriptase and protease sequences.
AB  - OBJECTIVE: We evaluated the prevalence of HIV-1 non-clade B over time in a
      formerly clade B-restricted area. Protease and reverse transcriptase regions of
      the pol gene were used for phylogenetic and recombination analysis and for clade
      assignment to HIV-1 A-D, F-H, J, and K strains of the M group. METHODS: The pol
      gene of 349 HIV-1 patients belonging to the Italian Cohort Naive for
      Antiretrovirals (ICONA) were genotypically analyzed to study the prevalence of
      antiretroviral-associated resistance mutations. All HIV-1 pol sequences and 32
      HIV reference strains were analyzed, including the reference strains for the
      major HIV-1 subtypes. The non-clade B sequences according to the HIV-1 Subtyping
      Tool program were further studied by a bootscan analysis (SimPlot) to investigate
      the likelihood of recombination between subtypes. RESULTS: Phylogenetic analysis
      detected 19 of 349 (5.4%) non-clade B subtypes. The proportions of patients
      carrying non-clade B virus before and after 1997 were 1.9% and 8.4%, respectively
      (p =.008). Among whites, heterosexual infection and female gender were
      significantly associated with the presence of non-clade B subtypes (p =.001
      and.005, respectively). Non-clade B HIV-1 was harbored by 14.5% of the
      heterosexuals who were found to be HIV-1 positive after 1997, 60% of whom were
      women. Bootscan analysis identified four strains as F, two as A, one as C, one as
      G, and 11 (57.9 %) as non-clade B recombinant subtypes. CONCLUSION: Detection of
      HIV-1 subtypes and intersubtype recombinants in a previously clade B-homogeneous
      area indicates that the HIV-1 epidemic is evolving in Italy and that
      heterosexuals and women are at increased risk of infection with non-clade B HIV-1
      subtypes. Sequences inferred from the pol gene yield to establish the subtype of
      circulating HIV-1 strains. As a consequence, genotyping of pol gene for testing
      resistance to antiretrovirals warrants concomitant surveillance of non-clade B
      subtypes.

PMID- 11511829
TI  - Lipodystrophy and insulin resistance in patients with HIV.

PMID- 11511830
TI  - Antitissue transglutaminase antibodies in HIV infection and effect of highly
      active antiretroviral therapy.

PMID- 11511831
TI  - Panniculitis. Part II. Mostly lobular panniculitis.
AB  - The second part of our review of panniculitis summarizes the clinicopathologic
      features of the mostly lobular panniculitides. Erythema induratum of Bazin
      (nodular vasculitis) represents the most common variant of lobular panniculitis
      with vasculitis, although controversy persists about the nature of the involved
      vessels. Mostly lobular panniculitides without vasculitis comprise a series of
      disparate disorders. These include sclerosing panniculitis that results from
      chronic venous insufficiency of the lower extremities; panniculitis with
      calcification of the vessel walls such as calciphylaxis and oxalosis; and
      inflammatory diseases with crystals within the adipocytes such as sclerema
      neonatorum, subcutaneous fat necrosis of the newborn, and poststeroid
      panniculitis. Connective tissue diseases, such as systemic lupus erythematosus
      and dermatomyositis, pancreatic diseases, and alpha(1)-antitrypsin deficiency may
      also show a mostly lobular panniculitis with characteristic histopathologic
      features. Lobular panniculitis may also be an expression of infections, trauma,
      or factitial causes involving the subcutaneous fat. Lipoatrophy refers to a loss
      of subcutaneous fat due to a previous inflammatory process involving the
      subcutis, and it may be the late-stage lesion of several types of panniculitis.
      In contrast, lipodystrophy means an absence of subcutaneous fat with no evidence
      of inflammation and often the process is associated with endocrinologic,
      metabolic, or autoimmune diseases. Finally, cytophagic histiocytic panniculitis
      is the term that has been used to describe two different processes: one is
      inflammatory, a lobular panniculitis, and the other one is neoplastic, a
      subcutaneous T-cell lymphoma. The only common feature of these two different
      processes is the presence of cytophagocytosis in the lesions. (J Am Acad Dermatol
      2001;45:325-61.) LEARNING OBJECTIVE: At the completion of this learning activity,
      participants should be familiar with the pathogenesis, clinical manifestations,
      histopathologic findings, and treatment options for the most frequent variants of
      the lobular panniculitides.

PMID- 11511832
TI  - Confocal scanning laser microscopy of benign and malignant melanocytic skin
      lesions in vivo.
AB  - BACKGROUND: The ability of physicians for early diagnosis of cutaneous melanomas
      is less than perfect, prompting research into noninvasive methods for diagnosis.
      OBJECTIVE: Our purpose was to evaluate confocal scanning laser microscopy (CSLM)
      for noninvasive imaging of benign and malignant melanocytic lesions in vivo.
      METHODS: Forty pigmented skin lesions (including adjacent normal skin as control)
      in vivo were imaged with near-infrared CSLM. The confocal images were correlated
      to histopathology. RESULTS: Nuclear, cellular, and architectural detail in the
      epidermis and superficial dermis is imaged with high resolution and contrast.
      Melanin causes the cytoplasm of pigmented cells to appear bright. Melanocytic
      nevi had cohesive nests of uniformly circular cells and increased microvascular
      blood flow. Melanomas had a polymorphous cytologic structure, containing
      atypical, pleomorphic cells in disarray and irregular dendritic cells.
      CONCLUSION: CSLM is capable of identifying distinct patterns and cytologic
      features of benign and malignant pigmented skin lesions in vivo. CSLM may be
      useful to noninvasively discriminate benign and malignant lesions in vivo.

PMID- 11511833
TI  - Balsam-related systemic contact dermatitis.
AB  - BACKGROUND: Positive patch tests to balsam of Peru (BOP) or fragrance mix (FM)
      suggest the possibility of systemic contact dermatitis from balsam-related foods
      and spices. OBJECTIVE: This was a retrospective study to determine whether
      avoidance of balsam-related foods results in an improvement of dermatitis in
      these patients. METHODS: A review of the records of all patients seen from July 1
      to Dec 31, 1998 with positive patch tests to BOP, FM, cinnamic aldehyde, and
      balsam of tolu was performed 9 to 14 months after their evaluation in a tertiary
      dermatology center. All patients were contacted via telephone to assess the
      status of their dermatitis and whether they were able to note any specific balsam
      related food allergies. RESULTS: A total of 75 patients were identified, and 71
      could be contacted. Fourteen were only allergic to BOP or FM on testing; 31 were
      positive to BOP/FM and other allergens with presumed relevance to BOP/FM; 26 were
      positive to BOP/FM and others with other allergens felt to be responsible for the
      dermatitis and were not placed on a BOP diet. Excluding this last group, 21 of 45
      (47%) had complete or significant improvement that they related to dietary
      modification. Ten did not modify their diet, with 8 reporting no improvement.
      Eight improved with fragrance or other allergen avoidance only, and 6 modified
      their diet unsuccessfully. Most commonly implicated foods included tomatoes,
      citrus, and spices. CONCLUSION: Almost half of the subjects with positive patch
      tests to BOP or FM who followed a BOP reduction diet reported significant to
      complete improvement of their dermatitis.

PMID- 11511834
TI  - Short-contact topical tretinoin therapy to stimulate granulation tissue in
      chronic wounds.
AB  - BACKGROUND: The use of retinoids in wound healing is increasing. It has been
      shown that retinoic acid reverses the inhibitory effects of glucocorticoids on
      wound healing and accelerates the formation of healthy granulation tissue.
      Pretreatment with tretinoin before epidermal injury such as chemical peeling and
      dermabrasion has shown accelerated wound healing. Enhanced healing of full
      thickness skin wounds has also been demonstrated in early wound healing studies.
      However, tretinoin therapy can be quite irritating. OBJECTIVE: Our purpose was to
      observe the clinical and histologic effects of topical tretinoin solution 0.05%
      applied directly to the wound beds of chronic leg ulcerations. METHODS: We report
      on the cases of 5 patients with long-standing leg ulcerations. All were treated
      with topical tretinoin solution 0.05% applied directly to the wound bed. The
      tretinoin solution was left in contact with the ulcer bed for a maximum of 10
      minutes daily and then rinsed with normal saline. Punch biopsy specimens were
      obtained from the wound beds at baseline and mid therapy. Standard wound care was
      continued throughout the study. RESULTS: In this study we found that as early as
      1 week after treatment with topical tretinoin solution 0.05%, there was increased
      granulation tissue first noted at the wound's edge. After 4 weeks of therapy with
      tretinoin, there was further stimulation of granulation tissue, new vascular
      tissue, and new collagen formation. CONCLUSION: Short-contact tretinoin therapy
      is a novel modality in which to treat chronic ulcers and stimulate the formation
      of granulation tissue.

PMID- 11511835
TI  - Natural course of physical and chronic urticaria and angioedema in 220 patients.
AB  - BACKGROUND: Information about spontaneous remission of chronic urticaria is
      limited. OBJECTIVE: To investigate the natural course of urticaria, we followed
      up 220 adults in a prospective study. METHODS: Patients were followed up for 1 to
      3 years to evaluate interventions, to detect latent causes, and to study the
      natural course of urticaria. The diagnosis was made by detailed history-taking as
      well as laboratory and provocation tests. RESULTS: Thirty-five percent of all
      patients were free of symptoms after 1 year. In 28.9% of patients, symptoms had
      decreased. Spontaneous remission occurred in 47.4% of the patients in whom no
      cause of their urticaria and/or angioedema could be identified and in only 16.4%
      of the patients with physical urticaria. A cause could be identified in 53.1% of
      the patients. Thirty-six percent of the patients had idiopathic urticaria.
      Chronic idiopathic urticaria combined with physical urticaria occurred in 10.9%.
      CONCLUSION: In general, the prognosis for spontaneous remission is reasonable,
      with the exception of the subgroup (33.2%) with physical urticaria.

PMID- 11511836
TI  - The penetration of 0.005% fluticasone propionate ointment in eyelid skin.
AB  - BACKGROUND: The use of corticosteroids to treat periorbital dermatoses carries
      significant risk of serious side effects such as glaucoma, cataracts, and
      blindness. Studies to assess levels of corticosteroid penetration in the eyelid
      are lacking. OBJECTIVE: We assessed corticosteroid penetration in eyelid skin in
      vitro to obtain information leading to the establishment of safer dosing
      regimens. METHODS: Fluticasone propionate ointment, 0.005%, was applied
      (approximately 2-5 mg/cm(2)) to samples of human eyelid skin, and penetration was
      assessed by using modified Franz diffusion cells. Drug concentration was
      determined at 12, 24, 36, and 48 hours after application by liquid chromatography
      tandem mass spectrometry. RESULTS: Only very small amounts of fluticasone
      propionate penetrated the skin (range, 0.618% +/- 0.339% to 1.467% +/- 0.695%).
      CONCLUSION: Further studies are warranted to examine the safety and efficacy of
      0.005% fluticasone propionate ointment for the treatment of eyelid dermatoses.

PMID- 11511837
TI  - Pointillist nevi.
AB  - BACKGROUND: Atypical melanocytic nevi and cutaneous melanoma are often marked by
      variation in color. However, there are examples of "benign" explanations for
      irregularities in pigmentation, such as perifollicular hypopigmentation or
      hyperpigmentation. OBJECTIVE: The purpose of this study was to correlate the
      clinical and histologic features of 3 unusual melanocytic nevi consisting
      exclusively of multiple, tiny, dark brown to black dots on a skin-colored
      background, which we have termed pointillist nevi. METHODS: Histologic
      examination was performed of the single pointillist nevus from each of 3 patients
      (all women; aged 28, 39, and 47 years). RESULTS: The diameters of the pointillist
      nevi were 2, 3.5, and 5.5 mm. Individual dots were approximately 0.1-0.25 mm.
      Each of the 3 nevi showed a different histologic correlate for the dots, either
      (1) discrete, densely pigmented, junctional melanocytic nests; (2) isolated
      dermal pigmented melanocytic nests; or (3) discrete clusters of melanophages in
      the papillary dermis. CONCLUSION: Pointillist nevi are benign melanocytic nevi
      with histologic correlates similar to those of the "brown globules" observed by
      dermoscopy in uniformly pigmented nevi. However, the dots seen in pointillist
      nevi can be visualized without magnification. The clinical and histologic
      features of pointillist nevi add to the spectrum of unusual patterns of
      pigmentation that may be encountered in benign melanocytic lesions.

PMID- 11511838
TI  - Radiation therapy for Bowen's disease: lessons for lesions of the lower
      extremity.
AB  - OBJECTIVE: A retrospective outcomes review of radiotherapy for Bowen's disease
      was performed to analyze all patients treated with radiation therapy between 1993
      and 1997 at the Naval Medical Center, San Diego. METHODS: Eleven patients with 16
      lesions were treated with a median time-dose-fractionation value of 105 (range,
      93-108). RESULTS: All 11 patients were without evidence of disease within 1 to 2
      months of completing treatment. Four of the 16 lesions (25%) were unhealed at
      time of last follow-up; the remainder healed with good cosmetic result. All
      unhealed lesions were on the lower extremity. Median follow-up was 27.5 months
      (range, 9-57 months). CONCLUSION: Radiation remains a good therapeutic option in
      selected patients with Bowen's disease, but caution should be exercised before
      selection of patients with lesions in potentially poor healing areas, such as the
      lower extremity.

PMID- 11511839
TI  - Evaluation of a new paraffin-reactive CD7 T-cell deletion marker and a polymerase
      chain reaction-based T-cell receptor gene rearrangement assay: implications for
      diagnosis of mycosis fungoides in community clinical practice.
AB  - BACKGROUND: T-cell deletion and T-cell receptor (TCR) gene rearrangement studies
      are helpful in the early diagnosis and subsequent management of mycosis fungoides
      (MF). However, this often requires fresh-frozen tissue that can be difficult to
      obtain and evaluate in community clinical practice. A new CD7 antibody, the most
      sensitive and specific T-cell deletion marker, and a new TCR-gamma gene
      rearrangement polymerase chain reaction (PCR) assay (TCR-gamma PCR) are now
      available on routine paraffin-embedded biopsy specimens. OBJECTIVE: Our purpose
      was to assess the utility of CD7 deletion and TCR-gamma PCR in the diagnosis of
      MF using routine paraffin-embedded biopsy material. METHODS: Cases of MF (n = 17)
      with matching frozen tissue immunohistochemistry and benign reactive dermatoses
      (lichen planus; n = 27) were assessed for CD7 (Clone: CD7-272) deletion and TCR
      gamma PCR using paraffin-embedded biopsy specimens. RESULTS: Excellent
      concordance comparing frozen and paraffin embedded CD7 immunostaining (88%) was
      observed. CD7 deletion and TCR-gamma PCR was sensitive (94%) and specific (96%)
      for a diagnosis of MF using paraffin-embedded biopsy specimens. CONCLUSION: In
      the diagnosis of MF, detection of CD7 deletion and monoclonal TCR rearrangements
      can be successfully performed in a cost-effective, timely fashion using routine
      formalin-fixed paraffin-embedded biopsy specimens.

PMID- 11511840
TI  - Microphthalmia transcription factor immunohistochemistry: a useful diagnostic
      marker in the diagnosis and detection of cutaneous melanoma, sentinel lymph node
      metastases, and extracutaneous melanocytic neoplasms.
AB  - BACKGROUND: Melanoma is the most lethal form of skin cancer. Diagnosis of
      amelanotic melanoma and detection of micrometastases in sentinel lymph nodes pose
      diagnostic and therapeutic dilemmas for the dermatopathologist and clinician.
      OBJECTIVE: The purpose of this article is to determine the utility of
      immunohistochemistry using antibodies specific for microphthalmia in the
      identification of melanocytic lesions in the skin, eye, central nervous system,
      and sentinel lymph nodes. METHODS: Paraffin-embedded, formalin-fixed specimens of
      cutaneous melanoma, including amelanotic melanoma and lentigo maligna melanoma,
      were stained with antibodies specific for microphthalmia. In addition, paraffin
      sections of extracutaneous lesions, including sentinel lymph nodes, uveal
      melanoma, and central nervous system melanocytomas, were stained with the
      specific microphthalmia antibody. RESULTS: All cutaneous melanomas stained
      positively with microphthalmia, as did uveal melanomas and central nervous system
      melanocytomas. These findings confirm the melanocytic origin of melanocytomas and
      uveal melanomas and demonstrate that microphthalmia staining can be used to
      establish melanocytic origin of neoplasms. In addition, micrometastases were
      easily detected in sentinel lymph nodes. CONCLUSION: Microphthalmia transcription
      factor immunohistochemistry is a valuable tool in the identification of
      melanocytic lesions in numerous sites. Use of this stain may facilitate detection
      of micrometastases in sentinel lymph nodes.

PMID- 11511841
TI  - Dapsone and sulfones in dermatology: overview and update.
AB  - In their 60-year history, dapsone and the sulfones have been used as both
      antibacterial and anti-inflammatory agents. Dapsone has been used successfully to
      treat a range of dermatologic disorders, most successfully those characterized by
      abnormal neutrophil and eosinophil accumulation. This article reviews and updates
      the chemistry, pharmacokinetics, clinical application, mechanism of action,
      adverse effects, and drug interactions of dapsone and the sulfones in
      dermatology.

PMID- 11511842
TI  - Pruritus and eosinophilia in a 14-year-old girl from Liberia.

PMID- 11511843
TI  - Guidelines of care for liposuction.

PMID- 11511844
TI  - Tuberous sclerosis. Part I. Clinical and central nervous system findings.

PMID- 11511845
TI  - Tuberous sclerosis. Part II. Musculoskeletal and visceral findings.

PMID- 11511846
TI  - Surgical pearl: Gentian violet-dyed sutures improve intraoperative visualization.

PMID- 11511847
TI  - Pigmented purpuric contact dermatitis from Disperse Blue 106 and 124 dyes.
AB  - The diagnosis of purpura pigmentosa progressiva in a female patient had to be
      changed to purpuric contact dermatitis after patch testing with textile dyes. A
      modified patch test performed in the area in which most of her skin lesions were
      located revealed a petechial reaction to the azo dye Disperse Blue 124/106. For
      evaluation of purpura pigmentosa progressiva we suggest a patch test with
      potential allergens, and, especially for textile dyes, a patch test at the lesion
      site may be helpful.

PMID- 11511848
TI  - Accidental bullous phototoxic reactions to bergamot aromatherapy oil.
AB  - Oil of bergamot is an extract from the rind of bergamot orange (Citrus aurantium
      ssp bergamia) that has a pleasant, refreshing scent; until a few years ago it had
      been widely used as an ingredient in cosmetics but was restricted or banned in
      most countries because of certain adverse effects. More recently, oil of bergamot
      preparations have been gaining renewed popularity in aromatherapy. Oil of
      bergamot possesses photosensitive and melanogenic properties because of the
      presence of furocoumarins, primarily bergapten (5-methoxypsoralen [5-MOP]).
      However, 5-MOP is also potentially phototoxic and photomutagenic. Despite its
      increasing application, there are only a few recent reports of phototoxic
      reactions to bergamot aromatherapy oil. We describe two patients with localized
      and disseminated bullous phototoxic skin reactions developing within 48 to 72
      hours after exposure to bergamot aromatherapy oil and subsequent ultraviolet
      exposure. One patient (case 2) had no history of direct contact with aromatherapy
      oil but developed bullous skin lesions after exposure to aerosolized (evaporated)
      aromatherapy oil in a sauna and subsequent UVA radiation in a tanning salon. This
      report highlights the potential health hazard related to the increasing use of
      psoralen-containing aromatherapy oils.

PMID- 11511849
TI  - Diffuse dermal angiomatosis of the breast: response to isotretinoin.
AB  - Dermal angiomatosis of the breast is an extremely rare disorder of unknown origin
      characterized by increased angiomatosis and ulceration. We report a case of a
      young woman whose disorder responded to isotretinoin. Our findings have potential
      relevance to the treatment of skin disorders in which ulceration is a prominent
      feature.

PMID- 11511850
TI  - Actinic keratoses--malignant or not?

PMID- 11511851
TI  - Surviving on a balsam-restricted diet: cruel and unusual punishment or medically
      necessary therapy?

PMID- 11511852
TI  - Genomics and drug discovery.
AB  - Genomics, the systematic study of all the genes of an organism, offers a new and
      much-needed source of systematic productivity for the pharmaceutical industry.
      The isolation of the majority of human genes in their most useful form is leading
      to the creation of new drugs based on human proteins, antibodies, peptides, and
      genes. Human Genome Sciences, Inc, was the first company to use the systematic,
      genomics approach to discovering drugs, and we have placed 4 of these in clinical
      trials. Two are described: repifermin (keratinocyte growth factor-2, KGF-2) for
      wound healing and treatment of mucositis caused by cancer therapy, and B
      lymphocyte stimulator (BLyS) for stimulation of the immune system. An anti-BLyS
      antibody drug is in advanced preclinical development for treatment of autoimmune
      diseases.

PMID- 11511853
TI  - Clearance can be a realistic expectation of psoriasis treatment.

PMID- 11511854
TI  - Mouse fingers, a new computer-related skin disorder.

PMID- 11511856
TI  - Female pattern hair loss.

PMID- 11511857
TI  - Possible mechanisms of miniaturization during androgenetic alopecia or pattern
      hair loss.
AB  - In androgenetic alopecia, or pattern hair loss, follicles undergo
      miniaturization, shrinking from terminal to vellus-like hairs. Traditionally,
      this process is thought to progress gradually over a number of follicular cycles.
      However, it is unlikely that miniaturization can be explained only by a series of
      progressively shorter anagen cycles. Simple calculations show that this process
      would take too long for significant miniaturization to occur secondary to shorter
      anagen cycles alone, especially in view of the latent lag period seen in pattern
      hair loss that occurs between the loss of a telogen hair and the appearance of an
      anagen hair. Evidence is presented to support a new concept that miniaturization
      is an abrupt, large-step process that also can be reversed in 1 hair cycle, as
      has been shown clinically, with confirmatory histologic evidence, in patients
      with pattern hair loss responding to finasteride treatment. It is hypothesized
      that the miniaturization seen with pattern hair loss may be the direct result of
      reduction in the cell number and, hence, size of the dermal papilla.

PMID- 11511858
TI  - Complexities of androgen action.
AB  - Androgens mediate a wide range of processes during embryogenesis and in the
      adult. In mammals, the principal androgens are testosterone and its 5alpha
      reduced metabolite, 5alpha-dihydrotestosterone (DHT). Although these androgenic
      hormones are diverse in character, it is believed that their effects are mediated
      via the protein products of a single androgen receptor gene encoded on the X
      chromosome. A great deal of information has now accumulated pertaining to the
      mechanisms by which nuclear receptors, such as the androgen receptor, modulate
      the activity of responsive genes. The studies have demonstrated the participation
      of a number of ancillary proteins in modulating activation or repression by
      nuclear receptors. In addition to studies focused on the mechanisms of nuclear
      receptor function, additional work has illuminated the mechanism by which
      androgens are metabolized in selected tissues. This information provides a
      perspective on the number of levels of complexity by which differential gene
      regulation by androgens may occur in different tissues and in different cell
      types.

PMID- 11511859
TI  - Polycystic ovary syndrome and insulin-resistant hyperinsulinemia.
AB  - In a broad sense, polycystic ovary syndrome (PCOS) may be considered to be
      synonymous with chronic unexplained hyperandrogenemia, which accounts for
      approximately 95% of hyperandrogenism in women. PCOS comprises a mosaic of
      classic and nonclassic forms, which may ultimately prove to have distinct genetic
      determinants. The hyperandrogenism appears to arise from generalized abnormal
      regulation (dysregulation) of steroidogenesis. This dysregulation seems to result
      from imbalance among the various extrinsic and intrinsic factors involved in the
      modulation of trophic hormone action. Hyperinsulinemia seems to be an important
      extrinsic factor in many cases of PCOS; it results from resistance to the effects
      of insulin on glucose metabolism. The elevation in insulin levels may precipitate
      hyperandrogenemia in genetically vulnerable individuals by unmasking latent
      abnormalities in the regulation of steroidogenesis. One of these may be a
      polycystic ovary gene that is expressed in the male as pattern baldness. Insulin
      also seems to be one of many factors that interact with androgen to regulate
      pilosebaceous unit development. Treatment of PCOS with antidiabetic insulin
      lowering agents may improve ovarian function and androgen levels; it remains to
      be determined whether it will benefit the pilosebaceous unit manifestations of
      the disorder.

PMID- 11511860
TI  - Ovarian hormones and adrenal androgens during a woman's life span.

PMID- 11511861
TI  - Estrogen production and action.
AB  - Estradiol production is most commonly thought of as an endocrine product of the
      ovary; however, there are many tissues that have the capacity to synthesize
      estrogens from androgen and to use estrogen in a paracrine or intracrine fashion.
      In addition, other organs such as the adipose tissue can contribute significantly
      to the circulating pool of estrogens. There is increasing evidence that in both
      men and women extraglandular production of C(18) steroids from C(19) precursors
      is important in normal physiology as well as in pathophysiologic states. The
      enzyme aromatase is found in a number of human tissues and cells, including
      ovarian granulosa cells, the placental syncytiotrophoblast, adipose and skin
      fibroblasts, bone, and the brain, and it locally catalyzes the conversion of
      C(19) steroids to estrogens. Aromatase expression in adipose tissue and possibly
      the skin primarily accounts for the extraglandular (peripheral) formation of
      estrogen and increases as a function of body weight and advancing age. Sufficient
      circulating levels of the biologically active estrogen estradiol can be produced
      as a result of extraglandular aromatization of androstenedione to estrone that is
      subsequently reduced to estradiol in peripheral tissues to cause uterine bleeding
      and endometrial hyperplasia and cancer in obese anovulatory or postmenopausal
      women. Extraglandular aromatase expression in adipose tissue and skin (via
      increasing circulating levels of estradiol) and bone (via increasing local
      estrogen concentrations) is of paramount importance in slowing the rate of
      postmenopausal bone loss. Moreover, excessive or inappropriate aromatase
      expression was demonstrated in adipose fibroblasts surrounding a breast
      carcinoma, endometriosis-derived stromal cells, and stromal cells in endometrial
      cancer, giving rise to increased local estrogen concentrations in these tissues.
      Whether systemically delivered or locally produced, elevated estrogen levels will
      promote the growth of these steroid-responsive tissues. Finally, local estrogen
      biosynthesis by aromatase activity in the brain may be important in the
      regulation of various cognitive and hypothalamic functions. The regulation of
      aromatase expression in human cells via alternatively used promoters, which can
      be activated or inhibited by various hormones, increases the complexity of
      estrogen biosynthesis in the human body. Aromatase expression is under the
      control of the classically located proximal promoter II in the ovary and a far
      distal promoter I.1 (40 kilobases upstream of the translation initiation site) in
      the placenta. In skin, the promoter is I.4. In adipose tissue, 2 other promoters
      (I.4 and I.3) located between I.1 and II are used in addition to the ovarian-type
      promoter II. In addition, promoter use in adipose fibroblasts switches between
      promoters II/I.3 and I.4 upon treatments of these cells with PGE(2) versus
      glucocorticoids plus cytokines. Moreover, the presence of a carcinoma in breast
      adipose tissue also causes a switch of promoter use from I.4 to II/I.3. Thus
      there can be complex mechanisms that regulate the extraglandular production of
      estrogen in a tissue-specific and state-specific fashion.

PMID- 11511862
TI  - Not quite dead enough: on bacterial life, culturability, senescence, and death.
AB  - A number of regulatory networks are functionally integrated in starving cells of
      Escherichia coli to reduce oxidation of target macromolecules and to enhance the
      cell's ability to withstand environmental insults. However, despite the fact that
      starving wild-type E. coli cells enhance their capacity to manage oxidative
      stress, the proteins of these cells become increasingly oxidized and the cells
      gradually lose their ability to reproduce. Indeed, it has been argued that
      starved and growth-arrested bacterial cells show the same signs of senescence as
      aging cells of higher organisms and that free radicals may be involved in the
      gradual loss of bacterial culturability observed in a stationary phase culture.
      Another model suggests that the apparent loss of viability of starved cells is a
      programmed and adaptive response in which the cells enter a reversible non
      culturable state; the theory of the formation of viable but non-culturable cells.
      Recent data concerning the physiology and biochemistry of starved E. coli cells
      favor the model that starvation-induced loss of culturability is the result of
      stochastic deterioration rather than a programmed and adaptive phenomenon, and
      these data will be reviewed here.

PMID- 11511863
TI  - Two distinct enzyme systems are responsible for tetrachloroethene and
      chlorophenol reductive dehalogenation in Desulfitobacterium strain PCE1.
AB  - Desulfitobacterium strain PCE1 is able to use tetrachloroethene and
      chloroaromatics as terminal electron acceptors for growth. Cell extracts of
      Desulfitobacterium strain PCE1 grown with tetrachloroethene as electron acceptor
      showed no dehalogenase activity with 3-chloro-4-hydroxyphenylacetate (Cl-OH
      phenylacetate) and other ortho-chlorophenolic compounds in an in vitro assay.
      Extracts of cells that were grown with Cl-OH-phenylacetate as electron acceptor
      dechlorinated tetrachloroethene at 10% of the dechlorination rate of Cl-OH
      phenylacetate. In both cell extracts dechlorination was inhibited by the addition
      of 1-iodopropane and dinitrogen oxide, inhibitors of cobalamin-containing
      enzymes. The enzymes responsible for tetrachloroethene and Cl-OH-phenylacetate
      dechlorination were partially purified. A 100-fold enriched fraction of
      chlorophenol reductive dehalogenase was obtained that mainly contained a protein
      with a subunit size of 48 kDa. The characteristics of this enzyme are similar to
      that of the chlorophenol reductive dehalogenase of D. dehalogenans. After partial
      purification of the tetrachloroethene reductive dehalogenase, a fraction was
      obtained that also contained a 48-kDa protein, but the N-terminal sequence showed
      no similarity with that of the chlorophenol reductive dehalogenase sequence or
      with the N-terminal amino acid sequence of tetra- and trichloroethene reductive
      dehalogenase of Desulfitobacterium strain TCE1. These results provide strong
      evidence that two different enzymes are responsible for tetrachloroethene and
      chlorophenol dechlorination in Desulfitobacterium strain PCE1. Furthermore, the
      characterization of partially purified tetrachloroethene reductive dehalogenase
      indicated that this enzyme is a novel type of reductive dehalogenase.

PMID- 11511864
TI  - Isolation and properties of obligately chemolithoautotrophic and extremely alkali
      tolerant ammonia-oxidizing bacteria from Mongolian soda lakes.
AB  - Five mixed samples prepared from the surface sediments of 20 north-east Mongolian
      soda lakes with total salt contents from 5 to 360 g/l and pH values from 9.7 to
      10.5 were used to enrich for alkaliphilic ammonia-oxidizing bacteria. Successful
      enrichments at pH 10 were achieved on carbonate mineral medium containing 0.6 M
      total Na(+) and < or =4 mM NH(4)Cl. Five isolates (ANs1-ANs5) of ammonia
      oxidizing bacteria capable of growth at pH 10 were obtained from the colonies
      developed on bilayered gradient plates. The cells were motile and coccoid, with
      well-developed intracytoplasmic membranes (ICPM) and carboxysomes. At pH 10.0,
      ammonia was toxic for growth at concentrations higher than 5 mM NH(4)Cl. The
      bacteria were able to grow within the salinity range of 0.1-1.0 M of total Na+
      (optimum 0.3 M). In media containing 0.3-0.6 M total Na(+), optimal growth in
      batch cultures occurred in the presence of a bicarbonate/carbonate buffer system
      within the pH range 8.5-9.5, with the highest pH limit at pH 10.5. At pH lower
      than 8.0, growth was slower, most probably due to decreasing free ammonia. The pH
      profile of the respiratory activity was broader, with limits at 6.5-7.0 and 11.0
      and an optimum at 9.5-10.0. In pH-controlled, NH(3)-limited continuous culture,
      isolate ANs5 grew up to pH 11.3, which is the highest pH limit known for ammonia
      oxidizing bacteria so far. This showed the existence of extremely alkali-tolerant
      ammonia-oxidizing bacteria in the soda lakes. Comparative 16S rDNA sequence
      analysis of the five isolates demonstrated that they possess identical 16S rDNA
      genes and that they are closely related to Nitrosomonas halophila (sequence
      similarity 99.3%), a member of the beta-subclass of the Proteobacteria. This
      affiliation was confirmed by comparative sequence analysis of the amoA gene,
      encoding the active-site subunit of the ammonia-monoxygenase, of one of the
      isolates. DNA-DNA hybridization data further supported that the soda lake
      isolates are very similar to each other and represent an alkali-tolerant
      subpopulation of N. halophila whose species description is herewith amended.

PMID- 11511865
TI  - Screening of basidiomycete fungi for the quinone-dependent sugar C-2/C-3
      oxidoreductase, pyranose dehydrogenase, and properties of the enzyme from
      Macrolepiota rhacodes.
AB  - Mycelial cultures of 76 strains of lignocellulose-degrading basidiomycete fungi
      were screened for the activity of pyranose dehydrogenase, a novel sugar
      oxidoreductase recently detected in Agaricus bisporus. Of these fungi, 37 strains
      belonging to seven phylogenetically related genera of mostly litter-decomposing
      Agaricales were positive for the dehydrogenase, based on activity assays towards
      D-glucose with 1,4-benzoquinone or ferricenium ion as electron acceptors, and on
      TLC/HPLC analyses of the reaction products. Lack of activity with O(2) as the
      oxidant, specificity for C-3 of D-glucose, and active extracellular secretion of
      the enzyme were used as criteria to differentiate pyranose dehydrogenase from
      pyranose 2-oxidase (EC 1.1.3.10), known to be produced by numerous wood-rotting
      fungi. Extracellular pyranose dehydrogenase from Macrolepiota rhacodes was
      heavily glycosylated. The enzyme was characterized as a 78-kDa flavoprotein under
      denaturing conditions and a 76-kDa native protein using gel filtration. This
      enzyme had a maximum extracellular activity of 4.1 U ml(-1) in 39-day liquid
      cultures. It exhibited broad selectivity for sugar substrates and oxidized D
      glucose (K(m)=1.82) exclusively at C-3 to 3-dehydro-D-glucose (D-ribo-hexos-3
      ulose), in contrast to pyranose dehydrogenases from Agaricus species, which acted
      at both C-3 and C-2 of D-glucose. The N-terminal sequence, AVVYRHPDEL, showed
      significant similarity with that reported for A. bisporus.

PMID- 11511866
TI  - Organization of genes responsible for the stereospecific conversion of hydantoins
      to alpha-amino acids in Arthrobacter aurescens DSM 3747.
AB  - Arthrobacter aurescens DSM 3747 hydrolyzes stereospecifically 5'-monosubstituted
      hydantoins to alpha-amino acids. The genes involved in hydantoin utilization
      (hyu) were isolated on an 8.7-kb DNA fragment, and by DNA sequence analysis eight
      ORFs were identified. The hyu gene cluster includes four genes: hyuP encoding a
      putative transport protein, the hydantoin racemase gene hyuA, the hydantoinase
      gene hyuH, and the carbamoylase gene hyuC. The four genes are transcribed in the
      same direction. Upstream of hyuP and in opposite orientation to the hyu genes,
      three ORFs were found showing similarities to cytochrome P450 monooxygenase
      (ORF1, incomplete), to membrane proteins (ORF2), and to ferredoxin (ORF3). ORF8
      was found downstream of hyuC and again in opposite orientation to the hyu genes.
      The gene product of ORF8 displayed similarities to the LacI/GalR family of
      transcriptional regulators. Reverse transcriptase PCR experiments and Northern
      blot analysis revealed that the genes hyuPAHC are coexpressed in A. aurescens
      after induction with 3-N-CH3-IMH. The expression of the hyu operon was not
      regulated by the putative regulator ORF8 as shown by gene disruption and mobility
      shift experiments.

PMID- 11511867
TI  - The C-terminal part of the surface-associated protein MopE of the methanotroph
      Methylococcus capsulatus (Bath) is secreted into the growth medium.
AB  - A protein with an apparent molecular mass of 46 kDa was detected as the major
      polypeptide in the culture medium of the biotechnologically important
      methanotrophic bacterium Methylococcus capsulatus (Bath). The protein cross
      reacted with polyclonal antibodies raised against the outer-membrane-associated
      protein MopE. The antiserum was used to identify a positive clone from a lambda
      gt11 library. The nucleotide sequence determined for the clone demonstrated that
      MopE and the secreted protein are encoded by the same gene, and that the secreted
      protein represents an N-terminally truncated form of MopE. By using monospecific
      antibodies against MopE in immunogold electron microscopy, the protein was
      localized at the cell surface and cell periphery. The mopE gene was expressed in
      Escherichia coli. The MopE protein synthesized was found in the periplasmic space
      of E. coli. No protein with sequence similarity over the entire length of MopE
      was detected in the databases, but some sequence similarity to the copper
      repressible CorA protein of the methanotroph Methylomicrobium albus (Berson and
      Lidstrom 1997) was observed for the C-terminal region of MopE.

PMID- 11511868
TI  - Characterization by genotypic methods of symbiotic Nostoc strains isolated from
      five species of Gunnera.
AB  - The genetic diversity of ten symbiotic Nostoc strains isolated from different
      Gunnera species was investigated. The strains were analyzed using molecular
      methods with different taxonomic resolutions, including restriction fragment
      length polymorphisms (RFLP) of the PCR-amplified 16S ribosomal gene and the 16S
      23S internal transcribed spacer (ITS) region combined with computer-assisted
      analyses. The functional gene hetR, assigned to heterocyst differentiation, was
      used for denaturing gradient gel electrophoresis. A high genetic diversity was
      observed among the isolates even in the conserved gene coding for the small
      ribosomal unit. No correlation was observed between clustering of cyanobacteria
      and the host species of Gunnera.

PMID- 11511869
TI  - Analysis of phenotypic diversity among host-independent mutants of Bdellovibrio
      bacteriovorus 109J.
AB  - Host-independent (H-I) mutants of the obligate bacterial parasite Bdellovibrio
      bacteriovorus were isolated from wild-type strain 109J. Seven H-I mutants
      differed in morphological features such as cell length (2-30 microm) and shape
      (short or long spirals or rod-like), plaque size, and pigmentation (from almost
      colorless to bright orange). The mutants exhibited widely different growth
      capabilities in rich medium, with biomass doubling times and final biomass
      varying by a factor of two or more. Growth was always enhanced by the addition of
      host cell extract or divalent cations to the growth medium, but the effect varied
      widely between the mutants. Analysis of the hit region, mutations in which were
      previously proposed to be associated with the H-I phenotype, revealed that
      changes in the nucleotide sequence in this region occurred only in three of the
      seven mutants.

PMID- 11511870
TI  - Detailed biosynthetic pathway to decaprenoxanthin diglucoside in Corynebacterium
      glutamicum and identification of novel intermediates.
AB  - Carotenogenic mutants of Corynebacterium glutamicum were analyzed for their
      carotenoid content. Mutant MV10 accumulated the same carotenoids as the wild
      type, decaprenoxanthin, decaprenoxanthin monoglucoside, and (2R,6R,2'R,6'R)
      decaprenoxanthin di-(beta-D)-glucoside, but in three-fold higher amounts. In
      addition, decaprenoxanthin diglucoside fatty acid esters and the intermediates
      nonaprene, 2-(3-methyl-2-butenyl)-epsilon,psi-carotene, and sarcinene, 2,2'-bis(3
      methyl-2-butenyl)-epsilon,epsilon-carotene were identified as minor carotenoids.
      The pink mutants MV40 and MV60 synthesized only lycopene. From another pink
      mutant, MV70, novel C(50)-carotenoids were isolated. By NMR and mass
      spectroscopy, nonaflavuxanthin, 2-(4-hydroxy-3-methyl-2-butenyl)-1,16-didehydro
      1,2-dihydro-psi,psi-carotene, and flavuxanthin, 2,2'-bis(4-hydroxy-3-methyl-2
      butenyl)-1,16,1',16'-tetradehydro-1,2,1',2'-tetrahydro-psi,psi-carotene, were
      identified. The identification of these intermediates revealed the detailed
      pathway for the formation of decaprenoxanthin derivatives in Corynebacterium
      glutamicum.

PMID- 11511871
TI  - DctA- and Dcu-independent transport of succinate in Escherichia coli:
      contribution of diffusion and of alternative carriers.
AB  - Quintuple mutants of Escherichia coli deficient in the C(4)-dicarboxylate
      carriers of aerobic and anaerobic metabolism (DctA, DcuA, DcuB, DcuC, and the
      DcuC homolog DcuD, or the citrate/succinate antiporter CitT) showed only poor
      growth on succinate (or other C(4)-dicarboxylates) under oxic conditions. At
      acidic pH (pH 6) the mutants regained aerobic growth on succinate, but not on
      fumarate. Succinate uptake by the mutants could not be saturated at physiological
      succinate concentrations (< or =5 mM), in contrast to the wild-type, which had a
      K(m) for succinate of 50 microM and a V(max) of 35 U/g dry weight at pH 6. At
      high substrate concentrations, the mutants showed transport activities (32 U/g
      dry weight) comparable to that of the wild-type. In the wild-type using DctA as
      the carrier, succinate uptake had a pH optimum of 6, whereas succinate uptake in
      the mutants was maximal at pH 5. In the mutants succinate uptake was inhibited
      competitively by monocarboxylic acids. Diffusion of succinate or fumarate across
      phospholipid membranes (liposomes) was orders of magnitude slower than the
      transport in the wild-type or the mutants. The data suggest that mutants
      deficient in DctA, DcuA, DcuB, DcuC, DcuD (or CitT) contain a carrier, possibly a
      monocarboxylate carrier, which is able to transport succinate, but not fumarate,
      at acidic pH, when succinate is present as a monoanion. Succinate uptake by this
      carrier was inhibited by addition of an uncoupler. Growth by fumarate respiration
      (requiring fumarate/succinate antiport) was also lost in the quintuple mutants,
      and growth was not restored at pH 6. In contrast, the efflux of succinate
      produced during glucose fermentation was not affected in the mutants,
      demonstrating that, for succinate efflux, a carrier different from, or in
      addition to, the known Dcu and CitT carriers is used.

PMID- 11511872
TI  - Molecular characterization and heterologous expression of hypCD, the first two
      [NiFe] hydrogenase accessory genes of Thermococcus litoralis.
AB  - The hypCD genes, encoding the counterparts of mesophilic proteins involved in the
      maturation of [NiFe] hydrogenases, were isolated from the hyperthermophilic
      archaeon Thermococcus litoralis. The deduced gene products showed 30-40% identity
      to the corresponding mesophilic proteins. HypC and HypD were synthesized by the
      T7 expression system. Heterologous complementation experiments were done in
      Escherichia coli and Ralstonia eutropha strains lacking functionally active hypC
      and hypD genes. Only the cytoplasmic hydrogenase of R. eutropha could be
      processed by HypD from T. litoralis. This was the first demonstration of
      mesophilic hydrogenase processing using a hyperthermophilic archaeal accessory
      protein to produce an active enzyme.

PMID- 11511873
TI  - Ultrasound examination of carotid and vertebral arteries.
AB  - Ultrasound is the most widespread diagnostic procedure in obstructive disease of
      the arteries supplying the brain. The combined non-invasive information on
      morphology and function makes duplex ultrasound the procedure of choice in
      screening and follow-up of carotid artery disease. This review deals with all
      relevant aspects of color duplex ultrasound of the carotids and the vertebral
      arteries. After a short introduction into the clinical background, the paper
      focuses on aspects of examination technique. In the main part of the review the
      relevant ultrasound findings in carotid artery disease are discussed. The
      different methods for grading stenoses of the internal carotid artery are
      explained in detail. Other relevant pathologies, such as vertebral artery
      disease, dissection and aneurysms, are briefly mentioned. The clinical value of
      ultrasound in the work-up of carotid and vertebral artery disease is briefly
      discussed in comparison with other imaging procedures.

PMID- 11511874
TI  - Colour Doppler sonography of limb arteries.

PMID- 11511875
TI  - Ultrasound of limb veins.
AB  - Several imaging modalities are available for studying limb veins. Presently, the
      non-invasive duplex compression ultrasound and color Doppler imaging have
      replaced contrast venography as first-choice imaging modality in suspected deep
      vein thrombosis. This review discusses the current role of sonography and
      suggests a diagnostic strategy that minimises the need for contrast venography.

PMID- 11511876
TI  - Ultrasound of diffuse liver disease and portal hypertension.

PMID- 11511877
TI  - Ultrasound of focal liver lesions.
AB  - This paper gives a comprehensive overview of ultrasound of focal liver lesions.
      Technical aspects such as examination technique and the use of Doppler modes as
      well as recent developments such as tissue harmonic imaging and microbubble
      contrast agents are discussed. The clinical significance and sonographic features
      of various liver lesions such as haemangioma, focal nodular hyperplasia, adenoma,
      regenerative nodule, metastasis, hepatocellular carcinoma and various types of
      focal infections are described. With the exception of cysts and typical
      haemangiomas, definitive characterisation of a liver lesion is often not possible
      on conventional ultrasound. This situation has changed with the recent advent of
      ultrasound contrast agents, which permit definitive diagnosis of most lesions.
      Contrast-enhanced sonography using recently developed contrast-specific imaging
      modes dramatically extends the role of liver ultrasound by improving its
      specificity in the detection and characterisation of focal lesions to rival CT
      and MRI.

PMID- 11511878
TI  - Ultrasound of the pancreas: update and controversies.
AB  - The pancreas is an organ that often presents difficulties for ultrasound
      exploration due to the interference of abdominal gas in the stomach and duodenum.
      However, with technical experience and the use of a variety of examination
      techniques, such as filling the stomach with water or cellulose suspension,
      changing patient's position, or scanning at different moments of respiration,
      such as suspended inspiration or expiration, it can be seen in its totality in a
      high percentage of patients. In our opinion, especially as new technical advances
      have been incorporated into US equipment (color power Doppler, harmonics, and US
      pulse inversion) and new contrast agents are available, US can compete with CT in
      this field. Ultrasound can be as useful as CT in most patients with pancreatitis
      and pancreatic neoplasms. Furthermore, Endoscopic sonography (ES), as well as
      intraoperative and laparoscopic techniques, are also excellent for visualizing
      malignant pancreatic lesions and have a special role in preoperative staging.
      Finally, US is a good technique to guide fine-needle biopsy of the pancreas and
      for aspiration of inflammatory fluid collections and abscesses. Although CT has
      played a major role to date, US is presently the most widely available and
      economical means to visualize the pancreas.

PMID- 11511879
TI  - Non-invasive characterisation of coronary lesion morphology and composition by
      multislice CT: first results in comparison with intracoronary ultrasound.
AB  - The reliable non-invasive detection of coronary artery disease (CAD) is a prime
      goal for future developments in clinical cardiology. In addition to the
      documentation of high-grade stenoses, the detection of vulnerable plaques is of
      major importance for risk stratification and early treatment to prevent plaque
      rupture. Recently, a new generation of fast spiral CT has been introduced using a
      multi-slice technique (MSCT), which is the first real quantum leap in CT since
      the introduction of spiral CT in the early 1990s. We report on non-invasive
      differentiation of coronary plaque morphology by MSCT in patients with lesions in
      the proximal left anterior descending artery (LAD). The results were compared
      with the findings of intracoronary ultrasound (ICUS). The ICUS and MSCT scans
      were analysed in 6 patients scheduled for ICUS-guided PTCA. One target lesion was
      selected in each patient. On ICUS, two lesions were classified as soft, two as
      intermediate and two as calcified according to established criteria based on
      echogenicity. By multislice CT, density measurements (expressed in Hounsfield
      Units, HU) were performed at 16 randomly selected areas within the plaques. The
      two soft plaques showed a mean density of 6+/-28 and -5+/-25 HU, the two
      intermediate plaques of 83+/-17 and 51+/-19 HU, and the two calcified plaques of
      489+/-372 and 423+/-111 HU. To our knowledge, this is the first report on non
      invasive characterisation of coronary lesions by MSCT. Plaque composition could
      be clearly differentiated and classified according to the ICUS results by
      determining tissue density within the lesions. Thus, this new technology holds
      promise for non-invasive risk assessment in patients with known or suspected CAD
      since also rupture-prone soft coronary lesions can be detected by use of this new
      technique.

PMID- 11511880
TI  - Spiral CT pneumocolon: applications, status and limitations.
AB  - CT pneumocolon is a promising new technique in the diagnosis and management of
      colon pathology. CT pneumocolon can detect (sensitivity >95%) and stage (accuracy
      79%) colorectal cancer and is very accurate in the differentiation of malignant
      from benign colonic pathologies. It has excellent detection rates for polyps >10
      mm in diameter. Several studies using 3D virtual colonoscopy have already proven
      its high sensitivity and specificity in polyp detection making this technique
      robust as a screening tool. The combined results for virtual colonoscopy, from
      all centres, show a sensitivity of >85% in the detection of polyps 10 mm or
      greater in size, 70-80% for 5-9 mm polyps and an overall specificity of 90%. CT
      pneumocolon is a safe, non-invasive and cost-effective method for detecting
      colonic carcinomas and adenomas and correctly identifying which patients need
      further colonoscopy. The technique is quick, well tolerated and non-operator
      dependent. It can also image the proximal colon when distal stenoses prevent
      endoscopic and barium examination. CT pneumocolon is able to identify the
      features and complications of inflammatory bowel disease. Further research is
      warranted to fully assess its impact in terms of a screening tool, acceptability,
      availability and cost benefit.

PMID- 11511881
TI  - CT features of malignant mucinous cystic tumors of the pancreas.
AB  - This study is aimed at evaluating which pre-operative findings at CT are
      prevailingly associated with histologically malignant appearance of mucinous
      cystic tumor (MCT) of the pancreas. The CT examinations of 52 female patients
      affected with pathologically proved MCT were retrospectively evaluated by two
      radiologists, blinded to the histopathological assessment of the biologic
      behavior (either benign or malignant). A multivariate logistic regression
      analysis was performed in order to identify the most important features
      associated with the malignant nature of MCT. Calcifications in the wall and/or in
      the septa, thick wall, and septations resulted in the most important features
      associated with malignancy. The simultaneous presence of all these radiological
      signs constitutes an almost "certain" marker of malignancy, being the risk equal
      to 0.95, whereas the simultaneous presence of at least two of them entails a risk
      of malignancy ranging from 0.56 to 0.74, according to the type of morphological
      features. On the other hand, the absence of the mentioned radiological features
      entails a negligible risk of malignancy (0.02). Mucinous cystic tumors
      characterized by multilocular macrocystic architecture, with thick wall and
      calcifications in the wall and/or the septa, present the highest risk of
      malignancy, and advocate prompt surgical intervention. When those signs are
      absent, the probability of malignancy is lower. In this case a non-operative
      management is possible.

PMID- 11511882
TI  - Malignant focal hepatic lesions complicating underlying liver disease: dual-phase
      contrast-enhanced spiral CT sensitivity and specificity in orthotopic liver
      transplant patients.
AB  - The aim of this study was to determine the accuracy of contrast-enhanced biphasic
      spiral CT as a screening tool in the preoperative evaluation of orthotopic liver
      transplant (OLT) patients. Spiral-CT examinations were performed before liver
      transplantation in 53 patients. Scans were retrospectively reviewed and compared
      with pathologic findings in fresh-sectioned livers. When findings between spiral
      CT and pathology were discordant, formalized livers were reexamined with lesion
      by lesion evaluation. Fresh pathologic evaluation revealed 23 liver lesions (16
      HCC, 7 macro-regenerative nodules). Malignancy was identified in 13 of 53
      patients (24.5%). Pre-transplantation spiral CT depicted 27 liver lesions (23
      HCC, 4 macro-regenerative nodules). Malignancy was suspected in 14 patients
      (26.4%). In 10 of 53 (18.9%), spiral CT and pathologic evaluation were
      discordant. Subsequent retrospective pathologic evaluation showed malignancy in 4
      additional patients. Spiral CT compared with the retrospective pathologic
      findings revealed 36 real-negative, 14 real-positive, 0 false-positive, and 3
      false-negative patients with malignancy. Sensitivity and specificity of spiral CT
      in detection of malignancy was 82 and 100%, respectively. Contrast-enhanced
      biphasic spiral CT is an accurate technique in the evaluation of patients
      preceding OLT. Routine fresh-sectioned liver pathologic findings are not as
      sensitive as previously estimated.

PMID- 11511883
TI  - Polysplenia associated with semiannular pancreas.
AB  - We report CT images of an asymptomatic, adult case of polysplenia syndrome
      associated with semiannular pancreas, intestinal malrotation, preduodenal portal
      vein, and agenesis of the upper abdominal segment of the inferior vena cava with
      azygous continuation. This rare combination of abdominal abnormalities would be
      mainly caused by congenital malrotation of lower abdominal organs.

PMID- 11511884
TI  - Malignant islet cell tumor of the pancreas associated with portal venous
      thrombus.
AB  - In this report, CT and MR findings of a malignant islet cell tumor of the
      pancreas associated with tumor thrombus in the portal vein is presented. Imaging
      findings revealed diffuse involvement of the body and tail of the pancreas by the
      tumor. The most unusual finding was that this invasive tumor was an insulinoma.

PMID- 11511885
TI  - Differentiation between benign and malignant findings on MR-mammography:
      usefulness of morphological criteria.
AB  - The purpose of this study was to evaluate the usefulness of morphological
      criteria in differentiating between benign and malignant lesions on MR
      mammography. Fifty-three women (18-82 years) with 62 lesions scheduled for
      excisional biopsy underwent dynamic contrast-enhanced MR-mammography using fast
      3D Gradient-Echo sequences in coronal orientation (axial orientation in seven
      patients). Histology revealed 44 malignant and 18 benign lesions. For each
      lesion, five radiologists evaluated four morphological features: lesion shape,
      irregularity of contour, homogeneity of contrast enhancement and presence of ring
      enhancement. For each feature a receiver operating characteristic (ROC) curve was
      generated with calculation of the area under the curve (AUC). Interobserver
      variability was evaluated by the kappa-coefficient. The most reliable
      morphological feature indicating malignancy was an irregular lesion contour with
      a sensitivity/specificity/AUC of 83%/76%/0.9 followed by inhomogeneous contrast
      enhancement (85%/42%/0.7) and the presence of ring enhancement (71%/53%/0.64).
      The average interobserver agreement for the different features ranged between
      0.35 and 0.4. Morphological criteria are useful features in MR-mammography for
      differentiating between benign and malignant lesions. However, due to the
      relatively high interobserver variability, standardization of terminology is
      important.

PMID- 11511886
TI  - MR imaging of the skin and nipple of the breast: differentiation between tumour
      recurrence and post-treatment change.
AB  - Contrast-enhanced MR imaging of the breast has been found to be valuable in the
      assessment of local recurrence of previously treated breast cancer. We looked
      specifically at the appearances of the skin and nipple of the treated breast in
      order to describe the appearances of post-treatment change and recurrence in this
      region. Thirty-nine women treated for breast cancer had MR imaging of one or both
      breasts reviewed retrospectively with particular attention to the nipple and
      skin. The skin and chest wall were assessed for patients with mastectomies. All
      available histology of the skin and/or nipple, obtained following MR imaging, was
      reviewed. In patients who did not undergo surgery following MR imaging, clinical
      follow-up was obtained. Six of 39 cases had nodular enhancing areas seen on MR
      imaging, which correlated with histology demonstrating tumour recurrence within
      the skin and/or nipple. Of the remaining 33 patients, changes of linear or
      diffuse enhancement were seen in the skin and/or nipple of 15 patients. These
      changes were shown to be benign post-treatment changes at surgery/biopsy in 4
      cases or by clinical follow-up in the remainder. In this article we demonstrate
      differing patterns of contrast enhancement within the skin and nipple in
      recurrent breast carcinoma vs. post-treatment changes. This suggests that
      contrast-enhanced MR imaging of the breast may be a useful tool in
      differentiating tumour recurrence from post-treatment changes within the skin and
      nipple.

PMID- 11511888
TI  - Computed tomography of diffuse lung disease: functional correlates.
AB  - An appreciation of functional and morphological characteristics is fundamental to
      the understanding of diffuse lung disease. The detailed information available
      from high-resolution computed tomography (HRCT) and the facility to subjectively
      or objectively quantify disease has elucidated the sometimes complex pulmonary
      function profiles of several diffuse lung diseases. The many reasons why
      correlations between the extent of HRCT abnormalities and physiological measures
      of disease may be less strong than expected and are considered in this review.

PMID- 11511887
TI  - Metastasis to the breast from extramammary malignancies: a report of four cases
      and a review of literature.
AB  - Breast metastases from extramammary tumours are rare with few cases reported.
      Four cases of metastasis to the breast are presented and the diagnostic problems
      of this condition are reviewed. Correlation between the histology of primary
      tumour and the cytology of breast metastatic tumour can avoid the surgical breast
      biopsy and unnecessary mastectomy. Metastasis to the breast has poor prognosis.

PMID- 11511889
TI  - Thin-section CT of the lung: influence of 0.5-s gantry rotation and ECG
      triggering on image quality.
AB  - The aim of this study was to determine if ECG triggering and a shorter
      acquisition time of 0.5-s rotation decrease cardiac motion artifacts of thin
      section CT of the lung. In 25 patients referred for thin-section thoracic CT, 1
      mm thin-section slices were performed with a scanning time of 0.5 s with ECG
      gating, 0.5 s and 1 s during the diastolic phase of the heart at five identical
      anatomical levels from the aortic arch to lung basis. At each anatomical level
      and for each lung, cardiac motion artifacts were graded independently on a four
      point scale by three readers. Patients were divided into two groups according to
      their heart rate. A four-way analysis of variance was used to assess differences
      between the three modalities. Mean cardiac motion artifacts scores were rated
      1.23+/-0.02, 1.47+/-0.02, and 1.79+/-0.02, at 0.5 s with ECG gating, 0.5 s
      without ECG gating, and 1 s, respectively (F=139, p<0.0001). At the four
      anatomical levels below the aortic arch, the left lung scores were greater than
      the right lung score for the three modalities. For the modality 0.5 s with ECG
      gating no difference of scores was found between patients grouped according to
      their cardiac frequency. The 0.5-s gantry rotation with or without ECG gating
      scans reduces cardiac motion artifacts on pulmonary thin-section CT images and is
      mainly beneficial for the lower part of the left lung.

PMID- 11511890
TI  - Digital chest radiography with a large-area flat-panel silicon X-ray detector:
      clinical comparison with conventional radiography.
AB  - This was a radiologists' preference study to compare a digital chest radiography
      system that utilizes a large-area silicon flat-panel detector with conventional
      radiography for visualizing anatomic regions of the chest. Conventional and
      digital posteroanterior (PA) and lateral chest radiographs were obtained in 115
      patients. The PA and lateral image pairs were compared independently by three
      radiologists rating the overall appearance, 11 anatomic regions in the PA, and 9
      in the lateral views. Statistical analysis was performed with the Wilcoxon signed
      rank test with Bonferroni-Holm adjustment (p=0.05). For the PA view, the digital
      system performed significantly better for the overall appearance and for all
      anatomic regions except for the peripheral pulmonary vasculature and hilum, where
      no significant difference was found. For the lateral digital images, the regions
      trachea, costodiaphragmatic recess, and hilum were rated significantly worse. The
      regions retrosternal and retrocardiac lung were rated significantly better. The
      other regions and the overall appearance showed no significant differences. The
      described digital chest radiography system showed statistically superior
      visualization of anatomic regions for PA and an ambiguous performance for lateral
      images as compared with conventional radiography. After changing some image
      processing parameters for the lateral view, this system may be suitable for
      digitalization of chest radiography.

PMID- 11511891
TI  - Reversible amiodarone-induced lung disease: HRCT findings.
AB  - The aim of this study was to describe thoracic high-resolution computed
      tomography (HRCT) findings of reversible amiodarone-induced lung disease (AILD).
      The thoracic HRCT of 20 symptomatic patients who were considered as having
      reversible AILD by the medical staff of our institution were retrospectively
      reviewed. The patient-selection criteria used were the development of new
      respiratory symptoms while receiving amiodarone, the exclusion of other
      respiratory and cardiac diseases, and the decrease of both respiratory symptoms
      and radiological abnormalities after cessation of amiodarone and corticotherapy.
      The CT data recorded were those usually sought infiltrative lung diseases. The
      radiological findings using chest film (n=20) and HRCT (n=4) follow-up was noted.
      All patients had ground-glass opacities, associated with consolidations (n=4),
      thin intralobular reticulations (n=5), or both (n=11), with a subpleural (n=18)
      or central (n=2) location. Eight patients had high-density areas and 13 had
      pleural thickening (n=13). Bronchial abnormalities included dilation (n=16) and
      wall thickening (n=19). After therapeutic management, the radiological follow-up
      showed complete (n=17) or incomplete (n=3) improvement. Ground-glass opacities
      associated with thin intralobular reticulations and/or subpleural consolidations
      and bronchial abnormalities are common HRCT findings in reversible AILD.

PMID- 11511892
TI  - Image quality vs. radiation dose for a flat-panel amorphous silicon detector: a
      phantom study.
AB  - The aim of this study was to investigate the image quality for a flat-panel
      amorphous silicon detector at various radiation dose settings and to compare the
      results with storage phosphor plates and a screen-film system. A CDRAD 2.0
      contrast-detail phantom was imaged with a flat-panel detector (Philips Medical
      Systems, Eindhoven, The Netherlands) at three different dose levels with settings
      for intravenous urography. The same phantom was imaged with storage phosphor
      plates at a simulated system speed of 200 and a screen-film system with a system
      speed of 160. Entrance surface doses were recorded for all images. At each
      setting, three images were read by four independent observers. The flat-panel
      detector had equal image quality at less than half the radiation dose compared
      with storage phosphor plates. The difference was even larger when compared with
      film with the flat-panel detector having equal image quality at approximately one
      fifth the dose. The flat-panel detector has a very favourable combination of
      image quality vs radiation dose compared with storage phosphor plates and screen
      film.

PMID- 11511893
TI  - Clinical evaluation of a new stationary high strip density antiscatter grid in
      comparison with a conventional moving grid: influence on image quality and
      patient radiation dose.
AB  - This study aimed to evaluate a new stationary 13/75 antiscatter grid in
      comparison with a moving 12/40 grid with regard to its influence on image quality
      and patient radiation dose. One hundred consecutive patients had plain films of
      the abdomen using a moving 12/40 grid and another 100 patients were examined with
      a stationary 13/75 grid (tube voltage 73 kV, film size 35 cm x 43 cm, film-screen
      system speed class 400). As an intraindividual comparison, radiographs of the
      abdomen with a film size of 18 cm x 43 cm were taken of 27 patients using both
      grid types for every patient. Patients' weight and dose-area product were
      recorded. Image quality was evaluated by a multireader study using standardized
      questionnaires and three- or five-level grading systems. Results showed that use
      of the 13/75 grid accords with the ALARA principle: measurement of the dose-area
      product demonstrated a dose saving of 24% for a film size of 35 cm x 43 cm and a
      saving of 34% for a film size of 18 cm x 43 cm without calling into question the
      diagnostic image quality. The mean scores of the 12/40 grid were lower for three
      out of six normal anatomic structures (P<0.05) among the 200 patients, indicating
      a loss of image quality with the 13/75 grid. Assessment of the intraindividual
      trial revealed reduced detectability of three out of four anatomical details when
      the 13/75 grid was employed. At the cost of a minor loss of image quality in
      comparison with the 12/40 grid, the new stationary grid provides a clear
      reduction of radiation dose under clinical circumstances.

PMID- 11511894
TI  - Prevention of generalized reactions to contrast media: a consensus report and
      guidelines.
AB  - The aim of this study was to document, using consensus methodology, current
      practice for prevention of generalized reactions to contrast media, to identify
      areas where there is disagreement or confusion and to draw up guidelines for
      reducing the risk of generalized contrast media reactions based on the survey and
      a review of the literature. A document with 165 questions was mailed to 202
      members of the European Society of Urogenital Radiology. The questions covered
      risk factors and prophylactic measures for generalized contrast media reactions.
      Sixty-eight members (34%) responded. The majority indicated that a history of
      moderate and severe reaction(s) to contrast media and asthma are important risk
      factors. The survey also indicated that patients with risk factors should receive
      non-ionic contrast media. In patients at high risk of reaction, if the
      examination is deemed absolutely necessary, a resuscitation team should be
      available at the time of the procedure. The majority (91%) used corticosteroid
      prophylaxis given at least 11 h before contrast medium to patients at increased
      risk of reaction. The frequency of the dosage varied from one to three times.
      Fifty-five percent also use antihistamine Hl, mainly administered orally and
      once. Antihistamine H2 and ephedrine are rarely used. All essential drugs are
      available on the emergency resuscitation trolley. Patients with risk factors are
      observed up to 30 min by 48% and up to 60 min by 43% of the responders.
      Prophylactic measures are not taken before extravascular use of contrast media.
      Prophylactic drugs are given to patients with a history of moderate or severe
      generalized reaction to contrast media. In patients with asthma, opinion is
      divided with only half of the responders giving prophylactic drugs. Aspirin, beta
      blockers, interleukin-2 and non-steroid anti-inflammatory drugs are not
      considered risk factors and therefore are not stopped before injection of
      contrast media. The survey showed some variability in rating of risk factors for
      generalized contrast medium reactions, and marked variability in the prophylactic
      measures used. There remain major areas of uncertainty, and there is insufficient
      data in the literature to guide practice. Some simple guidelines for prophylaxis
      of generalized contrast medium reactions are proposed.

PMID- 11511895
TI  - SKIBO diseases: a concept to avoid bloody diagnostic procedures in ambiguous
      skeletal lesions.
AB  - In cases with an "atypical" radiologic pattern-osteolytic as well as
      osteosclerotic or mixed - the radiologist should pay attention to the patient's
      skin. There he will often find specific changes that are the key to a correct
      interpretation of the radiologic abnormalities. In such cases the synopsis is of
      more value in differential diagnosis than more or less unspecific histologic
      findings. Entities with a non-arbitrary conjunction of changes of the skin and
      bones we call SKIBO diseases. Some of them have a high potential for mimicking
      malignant bone lesions, often with the consequence of unnecessary biopsies. In
      this article we present the typical dermatologic and radiologic signs and
      symptoms of neurofibromatosis, sarcoidosis and pustulotic arteroosteitis (PAO)
      with special focus on such skeletal lesions that may mimic malignancy.

PMID- 11511896
TI  - Efficient radiological assessment of the internal snapping hip syndrome.
AB  - The aim of this study was to evaluate the diagnostic value/significance of
      various imaging techniques for demonstrating the underlying causative pathology
      of clinically suspected internal snapping hip syndrome. We intended to define the
      most efficient diagnostic imaging algorithm that leads to a specific definite
      therapy for this rare hip disorder. The imaging studies of 54 patients (43 women,
      11 men, average age 58 years) with the clinical suspicion of internal snapping
      hip syndrome were compared for their diagnostic value/significance for finding
      the underlying pathology. Radiological workup included plain radiographs of the
      pelvis and hip joints (n=54), ultrasound (US) of the hip joints (n=29), computed
      tomography (CT) of the pelvis and proximal femur (n=17), and magnetic resonance
      imaging (MRI) of the pelvis/hip joint (n=21). In order to establish an efficient
      diagnostic algorithm we compared the diagnostic value of each imaging technique
      alone and in combination with the other methods. The underlying causative
      pathology could be established in 37% of patients (n=20) by the use of
      conventional radiographs alone and in 46% of the patients (n=25) by US alone, and
      in combination in 83% of the patients (n=45). By adding CT to the radiological
      workup, we established final diagnosis in 88% (in combination with X-ray;
      n=15/17) and 94% (together with X-ray and US; n=16/17) of the patients. Whenever
      MR imaging was used a causative pathology was found in all patients (100%; n=21).
      The most efficient radiological algorithm in the assessment of patients with
      internal snapping hip syndrome is the combination of plain radiography and US. MR
      imaging can be retained for unresolved and difficult cases.

PMID- 11511897
TI  - Bone marrow changes adjacent to the sacroiliac joints after pelvic radiotherapy
      mimicking metastases on MRI.
AB  - Radiation-induced changes in the sacroiliac joints mimicking metastases on MR
      images were evaluated. Twelve patients who received radiotherapy to the pelvic
      region due to pelvic malignancy were included in the study. All patients had
      undergone external beam radiation therapy to the pelvic region, and 2 patients
      received supplementary internal radiation. The changes in the sacroiliac joints
      were evaluated. Computed-tomography-guided core bone biopsy from the bone marrow
      was taken from their corresponding MR sections in 5 of the patients. T1
      hypointense and T2 hyperintense areas with ill-defined margins in the bone marrow
      adjacent to the sacroiliac joints were observed in all patients. On bone
      scintigraphy all the lesions demonstrated increased activity. Other radiological
      modalities excluded fracture, soft tissue mass, and osseous destruction. Bone
      biopsies demonstrated peritrabecular fibrosis and inflammatory cell infiltration.
      Patients receiving radiotherapy to the pelvis may demonstrate T1 hypointense/T2
      hyperintense, ill-defined postradiotherapeutic benign changes in the sacroiliac
      joints. In the absence of any other signs of disease progression and when the
      imaging pattern is typical, close radiological follow-up should be sufficient to
      rule out metastases.

PMID- 11511898
TI  - Digital radiography with a large-scale electronic flat-panel detector vs. screen
      film radiography: observer preference in clinical skeletal diagnostics.
AB  - The imaging performance of a recently developed digital flat-panel detector
      system was compared with conventional screen-film imaging in an observer
      preference study. In total, 34 image pairs of various regions of the skeleton
      were obtained in 24 patients; 30 image pairs were included in the study. The
      conventional images were acquired with 250- and 400-speed screen-film
      combinations, using the standard technique of our department. Within hours, the
      digital images were obtained using identical exposure parameters. The digital
      system employed a large-area (43x43 cm) flat-panel detector based on amorphous
      silicon (Trixell Pixium 4600), integrated in a Bucky table. Six radiologists
      independently evaluated the image pairs with respect to image latitude, soft
      tissue rendition, rendition of the periosteal and enosteal border of cortical
      bone, rendition of cancellous bone and the visibility of potentially present
      pathological changes, using a subjective five-point scale. The digital images
      were rated significantly (p=0.001) better than the screen-film images with
      respect to soft tissue rendition and image latitude. Also the rendition of the
      cancellous bone and the periosteal and enosteal border of the cortical bone was
      rated significantly (p=0.05) better for the flat-panel detector. The visibility
      of pathological lesions was equivalent; only large-area sclerotic lesions (n=2)
      were seen superiorly on screen-film images. The new digital flat-panel detector
      based on amorphous silicon appears to be at least equivalent to conventional
      screen-film combinations for skeletal examinations, and in most respects even
      superior.

PMID- 11511899
TI  - Cerebral venous thrombosis in childhood.
AB  - This was a retrospective study to determine different etiologies of cerebral
      venous thrombosis (CVT) in childhood and to correlate extent and location of
      thrombosis with the etiology and the age of the child as well as the final
      outcome. In addition, the radiologic approach is discussed. This was a
      retrospective analysis of 19 children with CVT. The children were examined by
      contrast-enhanced dynamic CT. Radiologic findings were correlated with the
      etiology of CVT. Cerebral venous thrombosis is not as infrequent in children as
      has been thought. Cerebral venous thrombosis in children can occur due to trauma
      (n=9), infections (n=7), or coagulation disorders (n=3). Extent and location of
      thrombosis, as well as complications, final outcome, and therapy, depend on the
      etiology. Computed tomography remains a valuable primary imaging modality in the
      diagnosis of CVT in the acutely injured or diseased child.

PMID- 11511900
TI  - Congenital midline cleft of the posterior arch of atlas: a rare cause of
      symptomatic cervical canal stenosis.
AB  - Developmental symptomatic C1 canal stenosis is very rare. We describe the
      computed tomography (CT) and magnetic resonance imaging (MRI) appearances in a 8
      year-old child who presented with progressive upper and lower limb neurological
      symptoms and in whom imaging revealed the medial posterior hemiarches of a bifid
      C1 to be inturned and compressing the cervical cord. This particular
      configuration of the posterior arch of atlas is frequently associated with other
      craniocervical bony anomalies and presents with neurological symptoms early in
      life. Early CT or MRI examination of patients with symptomatic posterior arch of
      C1 defects is necessary, in order to detect such an appearance, since surgical
      treatment may prevent neurological deterioration.

PMID- 11511901
TI  - Intracranial hemorrhage: principles of CT and MRI interpretation.
AB  - Accurate diagnosis of intracranial hemorrhage represents a frequent challenge for
      the practicing radiologist. The purpose of this article is to provide the reader
      with a synoptic overview of the imaging characteristics of intracranial
      hemorrhage, using text, tables, and figures to illustrate time-dependent changes.
      We examine the underlying physical, biological, and biochemical factors of
      evolving hematoma and correlate them with the aspect on cross-sectional imaging
      techniques. On CT scanning, the appearance of intracranial blood is determined by
      density changes which occur over time, reflecting clot formation, clot
      retraction, clot lysis and, eventually, tissue loss. However, MRI has become the
      technique of choice for assessing the age of an intracranial hemorrhage. On MRI
      the signal intensity of intracranial hemorrhage is much more complex and is
      influenced by multiple variables including: (a) age, location, and size of the
      lesion; (b) technical factors (e.g., sequence type and parameters, field
      strength); and (c) biological factors (e.g., pO2, arterial vs. venous origin,
      tissue pH, protein concentration, presence of a blood-brain barrier, condition of
      the patient). We discuss the intrinsic magnetic properties of sequential
      hemoglobin degradation products. The differences in evolution between extra- and
      intracerebral hemorrhages are addressed and illustrated.

PMID- 11511902
TI  - Differentiation between high-grade glioma and metastatic brain tumor using single
      voxel proton MR spectroscopy.
AB  - The purpose of this study was to clarify the efficacy of single-voxel proton
      magnetic resonance spectroscopy (MRS) in differentiating high-grade glioma from
      metastasis. Thirty-one high-grade gliomas (11 anaplastic gliomas and 20
      glioblastomas) and 25 metastases were studied. Proton MRS was performed using
      point-resolved spectroscopy with echo times (TEs) of both 136 and 30 ms. The
      peaks for lipid were evaluated at short TE, and those for N-acetyl-aspartate
      (NAA), creatine (Cr), and choline-containing compounds (Cho) were assessed at
      long TE. All the tumors exhibited a strong Cho peak at long TE. Twenty-one of 25
      metastases showed no definite Cr peak. The remaining 4 metastases showed NAA and
      Cr peaks; however, the presence of NAA and relatively high NAA/Cr ratio (1.58+/
      0.56) indicated normal brain contamination. All the gliomas, except for a single
      glioblastoma, showed a Cr peak with (n=16) or without (n=14) NAA. At short TE all
      metastases and glioblastomas showed definite lipid or lipid/lactate mixture, but
      anaplastic gliomas showed no definite lipid signal. Intratumoral Cr suggests
      glioma. Absence of Cr indicates metastasis. Definite lipid signal indicates
      cellular necrosis in glioblastoma and metastasis, and no lipid signal may exclude
      metastases.

PMID- 11511903
TI  - Noninvasive follow-up of GDC-treated saccular aneurysms by MR angiography.
AB  - The aim of this study was to determine sensitivity and specificity of magnetic
      resonance angiography (MRA) for the assessment of durable occlusion of
      intracranial aneurysms with Guglielmi detachable coils (GDC) and to point out the
      influence of MRA results in re-intervention strategies. Forty-five patients with
      54 aneurysms that were previously treated by endovascular occlusion with GDC were
      selected for this study. All patients underwent digital subtraction angiography
      (DSA) and MRA examinations on the same day. The time-of-flight MRA studies were
      performed on a 1-T scanner. The MRA images were first read by radiologists who
      were not aware of the DSA results. In a second consensus reading by the
      neuroradiologists who had performed all interventional procedures of this series,
      the decision was made as to whether re-treatment was necessary. The distribution
      of aneurysm sizes, configurations and treatment results were sufficient for an
      unbiased evaluation. The first blinded evaluation revealed a sensitivity of 71%
      and a specificity of 95% for MRA assessment of aneurysm reperfusion. In the
      second consensus reading, the sensitivity increased to 92% and the specificity
      was 98%. The blinded reading indicates that MRA is a useful adjunct to DSA for
      the assessment of durable results after endovascular treatment of intracranial
      aneurysms. In the consensus reading it became obvious that sensitivity and
      specificity of MRA can be increased to 92 and 98%, respectively, if the results
      were evaluated by experienced neuroradiologists, including prior knowledge of all
      other examinations. We have already increased the follow-up intervals for DSA and
      use MRA intermittently, based on these results.

PMID- 11511904
TI  - CT and MRI characteristics of ossification of the ligamenta flava in the thoracic
      spine.
AB  - The purpose of this study was to compare MRI findings with CT findings of mass
      forming calcification/ossification of the thoracic ligamenta flava (OTLF). Twenty
      one Chinese patients presented with clinical evidence of chronic and progressive
      thoracic spinal cord compression which included: difficulty in walking; weakness;
      and/or numbness of the extremities, back pain, and lower extremity paresthesias.
      Axial and sagittal T1-weighted imaging (T1WI) and T2-weighted imaging (T2WI) were
      performed through the thoracic spine on a 1.0-T Impact unit (Siemens, Erlangen,
      Germany). Axial CT was obtained with 5-mm contiguous sections through the
      thoracic region. Decompressive surgery with resection of the OTLF were carried
      out in all patients. Low signal intensity of the mass-forming OTLF was
      demonstrated at a single level (n=1) or at multiple levels (n=20) on both T1WI
      and T2WI. The distribution of OTLF was bilateral at all levels identified in 6
      cases, unilateral at all levels in 5 patients, and both unilateral and bilateral
      at different levels in 10 cases. Ossification of the thoracic ligamenta flava
      involved the upper thoracic spine (T1-4) in 3 cases, midthoracic spine (T5-8) in
      3 cases, lower thoracic spine (T9-12) in 10 cases, and more than one thoracic
      spinal subregion in 5 cases. Computed tomography confirmed the MR findings
      regarding the location and distribution of OTLF in all cases, as well as the
      associated evidence of central spinal canal stenosis. In addition, 5 patients
      revealed associated ossification of the posterior longitudinal ligament. All
      patients demonstrated gradual, but incomplete, clinical improvement of the
      radiculomyelopathy following decompressive surgery. Ossification of the posterior
      longitudinal ligament resulting in thoracic central spinal canal stenosis and
      clinical radiculomyelopathy is not uncommon in the Asian people. Ossification of
      the thoracic ligamenta flava can be accurately evaluated equally well by CT and
      MR with regard to level(s) and side(s) of involvement, as well as to the relative
      degree of central spinal canal stenosis and the associated compression of the
      thoracic spinal cord.

PMID- 11511905
TI  - MRI findings of extramedullary haemopoiesis.
AB  - Extramedullary haemopoiesis (EH) is a compensatory process associated with
      chronic haemolytic anaemia. It is rare, however, for such an abnormality to cause
      spinal cord compression. We present two patients with known beta-thalassaemia
      intermedia who developed spinal cord compression due to masses of extramedullary
      haematopoietic tissue in the epidural space of the thoracic spine. The EH masses
      were diagnosed by MRI as an isointense epidural lesion on both T1- and T2
      weighted images, compressing severely the spinal cord. After administration of a
      paramagnetic agent, an intermediate enhancement of the masses was evident. All
      the vertebral bodies had low to intermediate signal intensity as a result of
      displacement of fatty marrow by haematopoietic marrow. Expansion of thoracic ribs
      with bilateral paravertebral masses were characteristic. A small dose of
      radiotherapy was given and marked improvement in neurological symptoms was
      evident. An MRI examination established shrinkage of the mass and decompression
      of spinal cord. The role of MRI in diagnosis of EH masses is essential and
      radiation therapy is a very effective treatment for this rare complication.

PMID- 11511906
TI  - MRI appearance of radiation-induced changes of normal cervical tissues.
AB  - Irradiation causes specific MRI changes in anatomic morphology and signal
      intensity. To avoid misinterpretation, it is important to consider the potential
      radiation changes of normal tissue in MRI. The aim of this study was to describe
      the detected radiation effects on normal cervical tissues in MRI. Pretreatment
      and posttreatment MRI of 52 patients with primary neck tumors were evaluated
      retrospectively. The MR imaging was performed before initiating radiotherapy and
      at the end of the treatment period. Patients underwent follow-up studies within
      24 months after the end of irradiation. Edema was the main radiation-induced
      effect. It was detected in the epiglottis, larynx, pharynx wall, retro- and
      parapharyngeal space, salivary glands, muscles, and subcutaneous tissue. In some
      cases the bone marrow of the mandible showed edema, due to osteonecrosis. We
      additionally detected fluid accumulation in the mastoid cells. Radiation caused
      volume reduction of the parotid gland, thickening of the pharynx wall, and fatty
      degeneration of bone marrow. Magnetic resonance imaging is an excellent method of
      depicting radiation-induced changes of normal tissue. Especially T2-weighted
      sequences allow the detection of even slight edema. It is important to be aware
      of the most common radiation-induced changes in MRI and to take them into account
      when assessing an examination.

PMID- 11511907
TI  - Ossifying lipoma of the parapharyngeal space: CT and MRI findings.
AB  - Ossifying lipomas independent of bone tissue are very rare. A literature review
      revealed that only few cases of ossifying lipoma independent of bone tissue have
      been reported. None of the cases have been reported in the international
      radiology literature. In addition, there are no reports concerning the MRI
      features of this entity. We describe CT and MRI findings in a case of ossifying
      lipoma of the parapharyngeal space.

PMID- 11511908
TI  - Cervical carcinoma: MR imaging with integrated endorectal/phased-array coils: a
      pilot study.
AB  - The purpose of this study was to investigate the value of using MRI with
      integrated endorectal/phased-array coils for the staging and determination of the
      extent of cervical carcinoma. Twenty-two consecutive patients with biopsy-proven
      cervical carcinoma underwent MRI with integrated endorectal/phased-array coils
      before treatment. Magnetic resonance imaging was compared with clinical staging
      using surgical and pathological results as the gold standard. Eighteen of 22
      patients underwent surgery. Seventeen of the 18 patients were correctly staged
      using an integrated endorectal/phased-array MRI with an overall staging accuracy
      of 94%. Fourteen of the 18 patients had a correct clinical staging with an
      overall staging accuracy of 78%. The overall accuracy of pelvic lymph node
      metastasis detection was 89% on MRI. These data showed that MRI using integrated
      endorectal/phased-array coils was more accurate than the clinical approach for
      the staging of cervical carcinoma. Magnetic resonance imaging using integrated
      endorectal/phased-array coils is a highly promising modality for detecting and
      staging cervical carcinomas.

PMID- 11511909
TI  - Preoperative staging of cervical carcinoma with MR imaging: a reappraisal of
      diagnostic accuracy and pitfalls.
AB  - The purpose of this study was to assess the diagnostic accuracy and pitfalls of
      MR imaging in preoperative staging of cervical cancer. Magnetic resonance imaging
      was performed to determine the tumor staging for 41 patients with cervical
      carcinoma emphasizing tumor size, parametrial invasion, vaginal invasion, and
      lymph node metastases. According to the correlation of MR findings with surgical
      pathological features, there was less than 5 mm discrepancy in the size in 29 of
      34 tumors (85.3%) that were larger than 1 cm. In assessing parametrial invasion,
      vaginal invasion and lymph node metastases, MR imaging had an accuracy of 95, 83,
      and 86%, respectively. In determining stage of disease and differentiating
      operable (< or =stage IIA) from advanced disease (> or =stage IIB), MR imaging
      had an accuracy of 82.9 and 93%. Pitfalls leading to staging errors included
      difficulties in differentiating cancer foci from surrounding tissue edema and
      detecting microscopic tumor extension. Magnetic resonance imaging is accurate in
      the evaluation of parametrial invasion and differentiation of operable from
      advanced disease. The ability of MR imaging to detect microscopic extra-cervical
      tumor extension and differentiate cancer foci from surrounding tissue edema is
      not as reliable.

PMID- 11511910
TI  - Neurilemoma of the renal capsule: MR imaging and pathologic correlation.
AB  - We report a case of neurilemoma arising from the renal capsule. Renal neurilemoma
      is an especially rare tumor, with only 15 cases previously reported. We attempted
      to correlate MR findings with microscopic components of the tumor. On T2-weighted
      images the solid part of the tumor was heterogeneous hyperintense. The MR signal
      intensity on T2-weighted images help estimate microscopic components of the renal
      neurilemoma.

PMID- 11511911
TI  - Skin rash in the hypogastric region during a regional chemotherapy for bladder
      carcinoma: CT and scintigraphic demonstration of a potential collateral pathway
      between the internal iliac and inferior epigastric arteries.
AB  - A 70-year-old man developed a skin rash in his right lower abdominal wall after
      an intra-arterial infusion chemotherapy for carcinoma of the bladder. A CT with a
      direct infusion of contrast material via the implanted reservoir showed a marked
      enhancement of the right inferior epigastric artery and a significantly large
      artery in the right inguinal region. Radionuclide imaging with a direct infusion
      of Tc-99m macroaggregated albumin (MAA) revealed an abnormal accumulation in the
      right anterior abdominal wall. These findings implied a collateral pathway from
      the right internal iliac artery to the right inferior epigastric artery, i.e.,
      the corona mortis.

PMID- 11511912
TI  - An ex vivo study on radiofrequency tissue ablation: increased lesion size by
      using an "expandable-wet" electrode.
AB  - The present comparative study was conducted to validate a newly developed
      "expandable-wet" electrode for an increased lesion size of radiofrequency
      ablation (RFA) on excised beef liver. The expandable-wet electrode, which allows
      interstitial hypertonic saline infusion through retractable curved needles, was
      compared with "expanded-dry" and "unexpanded-wet" electrodes for RFA lesion size
      and other parameters. A total of 120 lesions were created under 50 W (groups A-C)
      and 90 W (groups A'-C') power control mode for 10 min at each ablation site with
      the following groups: group A and A' of expanded-dry electrode (needles deployed
      but saline uninfused); group B and B' of unexpanded-wet electrode (saline infused
      but needle undeployed); and group C and C' of expanded-wet electrode (needles
      deployed and saline infused). Together with lower impedance and higher power
      output, the lesion size in group C (5.3+/-0.4 cm) and C' (6.0+/-1.0 cm) were
      significantly larger (P<0.01) than that in group A (3.3+/-0.3 cm) and A' (2.0+/
      0.2 cm), and group B (3.8+/-1.0 cm) and B' (2.6+/-0.4 cm). The RFA lesion size
      can be significantly enlarged when the expandable electrode is complemented with
      interstitial hypertonic saline infusion. This design may improve the efficacy of
      RF tumor ablation.

PMID- 11511916
TI  - Linkage and association to candidate regions in Swedish atopic dermatitis
      families.
AB  - We have studied, in 406 families with at least two siblings affected with atopic
      dermatitis (in total 1514 individuals) from the Swedish population, linkage and
      association to five chromosomal regions (2q35, 5q31-33, 6p21, 11q13 and 14q11)
      previously implicated in atopic diseases. The region on 14q11 gave evidence for
      linkage to atopic dermatitis (NPL-score: 2.36, P<0.009). In the 11q13 region,
      there was a clear association to an intragenic marker in the beta-subunit of the
      high-affinity IgE receptor for raised allergen-specific serum IgE levels
      (P<0.009). When a quantitative variable for the severity of atopic dermatitis was
      studied, evidence was found in favour of linkage to the 5q31-33 region, with the
      highest Z-score (2.06) close to the marker D5S458 (P<0.005).

PMID- 11511917
TI  - The polyglutamine motif is highly conserved at the Clock locus in various
      organisms and is not polymorphic in humans.
AB  - Circadian rhythms play a central role in diverse physiological phenomena and the
      recent years have witnessed the identification of a number of genes responsible
      for the maintenance of these rhythms. One of these is the Clock gene, which was
      first identified in mouse and subsequently in a large number of organisms,
      including humans. The human Clock gene has been proposed as a possible candidate
      for disorders affected by alterations of circadian rhythm, including bipolar
      disorder and schizophrenia. This gene contains a highly conserved polyglutamine
      motif, that in humans is coded for by CAG repeats. In view of the involvement of
      CAG repeat expansion in a number of neuro-psychiatric disorders, we have sought
      to determine the polymorphism status of CAG repeats at the Clock locus in humans.
      Our analysis of 190 unrelated individuals, who included patients suffering from
      bipolar disorder and schizophrenia, indicated that the repeat, which consisted of
      6 CAG triplets, was not polymorphic in humans. An analysis of the repeat in non
      human primates and other organisms revealed that the glutamine stretch is
      shortest in humans and baboons, and longest in Drosophila and zebrafish. A study
      of various Drosophila species revealed that the repeat number is highly
      polymorphic, ranging from 25 to 33 pure glutamine repeats. Unlike most other
      microsatellites, the CAG repeat stretch at the Clock locus in humans is smaller
      than its homologues in non-human primates. We propose that glutamine repeat size
      is functionally important in this gene and thus tightly regulated. The variation
      in repeat number is probably deleterious to the individual, resulting in the
      maintenance of a short and invariable repeat structure in the human population.

PMID- 11511918
TI  - Recombination in the pseudoautosomal region in a 47,XYY male.
AB  - Males with a 47,XYY karyotype generally have chromosomally normal children,
      despite the high theoretical risk of aneuploidy. Studies of sperm karyotypes or
      FISH analysis of sperm have demonstrated that the majority of sperm are
      chromosomally normal in 47,XYY men. There have been a number of meiotic studies
      of XYY males attempting to determine whether the additional Y chromosome is
      eliminated during spermatogenesis, with conflicting results regarding the pairing
      of the sex chromosomes and the presence of an additional Y. We analyzed
      recombination in the pseudoautosomal region of the XY bivalent to determine
      whether this is perturbed in a 47,XYY male. A recombination frequency similar to
      normal 46,XY men would indicate normal pairing within the XY bivalent, whereas a
      significantly altered frequency would suggest other types of pairing such as a YY
      bivalent or an XYY trivalent. Two DNA markers, STS/STS pseudogene and DXYS15,
      were typed in sperm from a heterozygous 47,XYY male. Individual sperm (23,X or Y)
      were isolated into PCR tubes using a FACStarPlus flow cytometer. Hemi-nested PCR
      analysis of the two DNA markers was performed to determine the frequency of
      recombination. A total of 108 sperm was typed with a 38% recombination frequency
      between the two DNA markers. This is very similar to the frequency of 38.3% that
      we have observed in 329 sperm from a normal 46,XY male. Thus our results suggest
      that XY pairing and recombination occur normally in this 47,XYY male. This could
      occur by the production of an XY bivalent and Y univalent (which is then lost in
      most cells) or by loss of the additional Y chromosome in some primitive germ
      cells or spermatogonia and a proliferative advantage of the normal XY cells.

PMID- 11511919
TI  - Opposite association of two PPARG variants with cancer: overrepresentation of
      H449H in endometrial carcinoma cases and underrepresentation of P12A in renal
      cell carcinoma cases.
AB  - Peroxisome proliferator activated receptor gamma (PPARgamma) is a nuclear hormone
      receptor that has been shown to regulate differentiation and cell growth. Studies
      of the differentiative effects of PPARgamma agonists on several cancer cell lines
      led to the hypothesis that dysfunction of PPARgamma contributes to tumorigenesis.
      These functional observations were strengthened by genetic evidence: somatic loss
      of-function mutations in PPARG, encoding PPARgamma, in sporadic colorectal
      carcinomas and somatic translocation of PAX8 and PPARG in follicular thyroid
      carcinoma. Recently overrepresentation of the H449H variant was found in a cohort
      of American patients with glioblastoma multiforme. The glioblastoma multiforme
      data suggest that PPARG contributes common, low-penetrance alleles for cancer
      susceptibility. To test this hypothesis in a broader range of cancers we examined
      a series of carcinomas of the cervix, endometrium, ovary, prostate, and kidney
      for germline sequence variation in PPARG. In addition to the two common sequence
      variants, P12A and H449H, there were five other sequence variants. P12A alleles
      were underrepresented in renal cell carcinoma patients compared to country-of
      origin race-matched controls (3.75% vs. 12.1%, P<0.04). In contrast, the H449H
      variant was overrepresented in individuals with endometrial carcinoma compared to
      controls (14.4% vs. 6.25%, P<0.02). These observations lend genetic evidence
      consistent with our hypothesis that PPARG serves as a common, low-penetrance
      susceptibility gene for cancers of several types, especially those
      epidemiologically associated with obesity and fat intake.

PMID- 11511920
TI  - AcroM fluorescent in situ hybridization analyses of marker chromosomes.
AB  - The presence of a de novo supernumerary marker chromosome (SMC) poses problems in
      genetic counseling. The consequences of the additional chromosomal material may
      range from harmless to detrimental. As the composition of a SMC cannot be
      deciphered by traditional banding analysis, sophisticated methods are needed for
      their rapid and detailed analyses. A new strategy is presented, which allows the
      elucidation of the composition of SMCs in one or two hybridizations. One
      hybridization, termed AcroM-FISH, involves a newly generated probe mix, which
      consists of painting probes for all acrocentric chromosomes, centromere probes
      for chromosomes 13/21, 14/22, 15, and a probe specific for rDNA, each labeled
      with a specific combination of fluorochromes. This probe mix is sufficient to
      characterize approximately 80% of all SMCs. For the other 20% of SMCs,
      chromosomes can be analyzed in a second hybridization by multicolor karyotyping,
      for example, multiplex FISH (M-FISH), to check for the presence of euchromatin of
      other chromosomes. The potential of AcroM-FISH was tested in various
      applications.

PMID- 11511921
TI  - Mutation analyses in 17 patients with deficiency in acid beta-galactosidase:
      three novel point mutations and high correlation of mutation W273L with Morquio
      disease type B.
AB  - An inherited deficiency in beta-galactosidase can result in GM1 gangliosidosis,
      with several phenotypes of generalized or chronic psychomotor deterioration, as
      well as in Morquio disease type B, a characteristic mucopolysaccharidosis free of
      neurological symptoms. We performed mutation analyses in 17 juvenile and adult
      patients from various European regions with a deficiency in beta-galactosidase
      and skeletal abnormalities. Fifteen of these had the Morquio B phenotype and have
      remained neurologically healthy until now while the two others exhibited
      psychomotor retardation of juvenile onset. A two-base substitution (851-852TG-
      >CT; W273L) was present in 14 of the 15 Morquio B cases. Even if one excludes
      alleles from patients with possible common descent, there was a much higher
      frequency (79%) among those with Morquio B phenotype for the W273L mutation than
      previously reported in the literature (37%). That the Morquio phenotype is also
      expressed in heterozygotes for W273L and alleles typically found in GM1
      gangliosidosis makes it possible to predict the phenotype and reliably detect
      heterozygotes. A single French patient had a novel missense point mutation
      (Q408P) together with a known mutation (T500A) while the mentally retarded
      patients were both heterozygous for two mutations known in chronic GM1
      gangliosidosis together with two novel missense point mutations (Y270D and H281Y)
      in the vicinity of W273L. Our results confirm the high impact of Trp 273 for the
      function of beta-galactosidase and the expression of the Morquio B phenotype. In
      addition, a second domain around the amino acids 400-500 may also be of
      significance.

PMID- 11511922
TI  - The position of t(11;22)(q23;q11) constitutional translocation breakpoint is
      conserved among its carriers.
AB  - The t(11;22)(q23;q11) translocation is the most common recurrent balanced
      translocation described in humans. Carriers are phenotypically normal and often
      go undetected until diagnosis as a result of infertility investigations or
      following the birth of chromosomally unbalanced offspring. Efficient diagnostics
      of t(11;22) is important for children born to carriers of the translocation and
      for prenatal and pre-implantation diagnosis. The translocation breakpoint on
      chromosome 22 is located within a region containing low copy repeats, and this
      site is one of the last unfilled gaps in the sequence of this chromosome. This
      autosome harbors multiple other low copy repeats, which have been entirely
      sequenced. We report a combined sequencing and fiber FISH breakpoint
      characterization in five translocation carriers. From one carrier a cosmid
      library was constructed, and two chimeric cosmids (cos4_der11 and cos6_der22)
      were sequenced, which showed that strong palindromes (or inverted repeats) occur
      on both chromosomes. The translocation breakpoints occur at the tip of both
      inverted repeats. The palindrome on chromosomes 22 and 11 is composed of 852 and
      166 bases, respectively. Four additional carriers were studied using fiber FISH
      with a resolution limit of 2 kb. Analysis of breakpoints on the DNA sequence
      level, or at the level of fiber FISH, indicate that they occur at the same
      position on both chromosomes in all five carriers. Using cos6_der22, PAC 158L19
      and BAC 3009A19, we demonstrate that FISH is an attractive alternative in
      molecular diagnostics of t(11;22), as PCR assays are not reliable, due to the
      presence of numerous copies of low copy repeats.

PMID- 11511923
TI  - Expression pattern, genomic structure and evaluation of the human SLC30A4 gene as
      a candidate for acrodermatitis enteropathica.
AB  - Slc30a4 is the fourth and last identified member of a mammalian proteins family
      presumably involved in the cellular transport of zinc, solute carrier family 30.
      The murine homologue of the human SLC30A4 gene has previously been investigated
      and found responsible for the lm, a phenotype due to zinc deficiency. According
      to the strong homology between mouse and human SLC30A4 coding sequences, and to
      the very similar clinical features encountered in the murine lm and in human
      acrodermatitis enteropathica, SLC30A4 has appeared to us to be a good candidate
      for acrodermatitis enteropathica. Here we detail the genomic structure of human
      SLC30A4 together with its localization on chromosome 15q15-q21. We also report
      the mutational analysis of human SLC30A4 in ten families with acrodermatitis
      enteropathica, which enabled us to exclude this gene from any involvement in the
      disorder of the patients examined.

PMID- 11511924
TI  - Identification and characterization of a tissue-specific silencer element in the
      first intron of the human acid maltase gene.
AB  - Deficiency of acid maltase (acid alpha-glucosidase), a lysosomal enzyme that
      degrades glycogen, results in glycogenosis type II, an autosomal recessive
      disease whose manifestations and severity largely depend on the level of residual
      enzyme activity. Previous studies have established that there are transcriptional
      control elements in the first intron; in particular a silencer responsive to Hes
      1 and YY1 has been identified in the human hepatoma line, HepG2. This region
      functions as an enhancer in human fibroblasts. Here we have localized a silencer
      active in fibroblasts to a nearby 25-bp element in intron 1. This element
      repressed thymidine kinase promoter activity by about 50% in both orientations in
      human fibroblasts. This silencer, as with the previous one, is tissue specific
      since constructs containing this region are inactive in HepG2 cells.
      Electrophoretic mobility shift assay revealed three proteins specifically binding
      to the element in fibroblasts, and site-directed mutagenesis analysis indicated
      that all the three proteins binding to the element contribute to the silencer
      function. The data may be helpful for designing therapy to increase the level of
      enzyme, particularly when, as in most adults with the disease, there is reduced
      production of structurally normal enzyme.

PMID- 11511925
TI  - Combined segregation-linkage analysis of plasma thrombin activatable fibrinolysis
      inhibitor (TAFI) antigen levels with TAFI gene polymorphisms.
AB  - By decreasing plasminogen binding to fibrin surface, the thrombin activatable
      fibrinolysis inhibitor (TAFI) has been hypothesized to constitute an early marker
      for atherothrombotic diseases. Previous studies have shown that plasma TAFI
      levels exhibit a high interindividual variability that is only poorly explained
      by lifestyle factors. Several polymorphisms of the TAFI gene have been described,
      and a combination of a C+1542G substitution in the 3' untranslated region and an
      Ala147Thr amino acid change has been shown to explain 60% of TAFI variability in
      a sample of unrelated individuals. A segregation-linkage analysis was performed
      to determine whether these polymorphisms are directly involved in the genetic
      regulation of TAFI levels, or whether they are only markers in linkage
      disequilibrium (LD) with unmeasured TAFI-linked quantitative trait loci (QTLs).
      The sample consisted of 97 healthy nuclear families from the Stanislas Cohort.
      The C+1542G and Ala147Thr polymorphisms were in complete negative LD, with minor
      allele frequencies of 0.27 and 0.28, respectively. Results of the segregation
      linkage analysis provided evidence of two TAFI-linked QTLs in LD with the two
      measured polymorphisms, which would explain 78% of the TAFI variance, as compared
      with 55% explained by the C+1542G and the Ala147Thr polymorphisms combined. The
      two putative QTLs would have minor allele frequencies of 0.45 and 0.32,
      respectively. The hypothesis that one of the measured polymorphisms is one of the
      QTLs was rejected. The putative QTLs also did not seem compatible with the other
      TAFI gene polymorphisms that we have previously described. More extensive
      sequencing of the TAFI gene is necessary to identify the functional variants.

PMID- 11511926
TI  - Archival, demographic and genetic studies define a Sardinian sub-isolate as a
      suitable model for mapping complex traits.
AB  - Genetic isolates represent exceptional resources for the mapping of complex
      traits but not all isolates are similar. We have selected a genetic and cultural
      isolate, the village of Talana from an isolated area of Sardinia, and propose
      that this population is suitable for the mapping of complex traits. A wealth of
      historical and archive data allowed the reconstruction of the demographic and
      genealogical history of the village. Key features of the population, which has
      grown slowly with no significant immigration, were defined by using a combination
      of historical, demographic and genetic studies. The genealogy of each Talana
      inhabitant was reconstructed and the main maternal and paternal lineages of the
      village were defined. Haplotype and phylogenetic analyses of the Y chromosome and
      characterisation of mitochondrial DNA haplogroups were used to determine the
      number of ancestral village founders. The extent of linkage disequilibrium (LD)
      was evaluated by the analysis of several microsatellites in chromosomal region
      Xq13.3, which was previously used to asses the extension of LD. Genealogical
      reconstructions were confirmed and reinforced by the genetic analyses, since some
      lineages were found to have merged prior to the beginning of the archival
      records, suggesting an even smaller number of founders than initially predicted.
      About 80% of the present-day population appears to derive from eight paternal and
      eleven maternal ancestral lineages. LD was found to span, on average, a 5-Mb
      region in Xq13.3. This suggests the possibility of identifying identical-by
      descent regions associated with complex traits in a genome-wide search by using a
      low-density marker map. The present study emphasises the importance of combining
      genetic studies with genealogical and historical information.

PMID- 11511927
TI  - Large-scale molecular screening for galactosemia alleles in a pan-ethnic
      population.
AB  - DNA samples from 4,796 subjects from diverse ethnic groups were screened for five
      frequently encountered galactose-1-phosphate uridyl transferase (GALT) mutations:
      S135L (cDNA nt 404C-->T, as numbered from the initiator ATG codon, with A=1);
      Q188R (cDNA nt 563A-->G); K285 N (cDNA nt 855G-->T); the Duarte variant, N314D
      (cDNA nt 940A-->G); and the Los Angeles variant, which contains L218L (cDNA nt
      652C-->T) and N314D. Among Whites, the gene frequency of the Q188R mutation was
      0.29%, and that of the K285 N mutation was 0.062%. Only one S135L mutation was
      encountered among 505 African-Americans (gene frequency 0.10%). The pan-ethnic
      gene frequencies of the Duarte and the Los Angeles variants were 5.1% and 2.7%,
      respectively. Both of these frequencies were significantly less among African
      Americans and Asians than among Whites and Hispanics. Native Americans revealed a
      higher incidence of the both variants. Based upon the gene frequency of the Q188R
      mutation in the White population, the birth incidence of classic galactosemia is
      estimated at one patient per 47,000 in the White population. This prevalence
      would be increased by inbreeding. It agrees well with the results from newborn
      screening programs and is only minimally higher than that reported in most
      studies, suggesting that most, if not all, infants with the galactosemia genotype
      are born and survive sufficiently long to be screened.

PMID- 11511928
TI  - Germ line insertion of mtDNA at the breakpoint junction of a reciprocal
      constitutional translocation.
AB  - Constitutional chromosomal translocations are relatively common causes of human
      morbidity, yet the DNA double-strand break (DSB) repair mechanisms that generate
      them are incompletely understood. We cloned, sequenced and analyzed the
      breakpoint junctions of a familial constitutional reciprocal translocation
      t(9;11)(p24;q23). Within the 10-kb region flanking the breakpoints, chromosome 11
      had 25% repeat elements, whereas chromosome 9 had 98% repeats, 95% of which were
      L1-type LINE elements. The breakpoints occurred within an L1-type repeat element
      at 9p24 and at the 3'-end of an Alu sequence at 11q23. At the breakpoint junction
      of derivative chromosome 9, we discovered an unusually large 41-bp insertion,
      which showed 100% identity to 12S mitochondrial DNA (mtDNA) between nucleotides
      896 and 936 of the mtDNA sequence. Analysis of the human genome failed to show
      the preexistence of the inserted sequence at normal chromosomes 9 and 11
      breakpoint junctions or elsewhere in the genome, strongly suggesting that the
      insertion was derived from human mtDNA and captured into the junction during the
      DSB repair process. To our knowledge, these findings represent the first
      observation of spontaneous germ line insertion of modern human mtDNA sequences
      and suggest that DSB repair may play a role in inter-organellar gene transfer in
      vivo. Our findings also provide evidence for a previously unrecognized
      insertional mechanism in human, by which non-mobile extra-chromosomal fragments
      can be inserted into the genome at DSB repair junctions.

PMID- 11511929
TI  - The Basques according to polymorphic Alu insertions.
AB  - Polymorphic Alu insertions provide a set of DNA markers of interest in human
      population genetics. Approximately 1000-2000 of these insertions have not reached
      fixation within the human genome. Each one of these polymorphic loci most
      probably resulted from a unique insertional event, and therefore all individuals
      possessing the insertion are related by descent not just state. In addition, the
      direction of mutational change is toward the gain of the Alu element at a
      particular locus. Therefore, the improved knowledge of both the ancestral state
      and the direction of mutational change greatly facilitates the analysis of
      population relationships. As a result, Alu insertion polymorphisms represent a
      significant tool for population genetic studies. In this study, polymorphic Alu
      insertions have been employed to ascertain phylogenetic relationships among
      Basque groups and worldwide populations. The Basques are considered to be a
      geographic isolate with a unique language and customs. They may be direct
      descendants of Cro-Magnon enclaves from the upper Paleolithic (38,000 to 10,000
      years). The Basques are distributed among narrow valleys in northeastern Spain
      with little migration between them until recently. This characteristic may have
      had an effect on allelic frequency distributions. With the aim of studying this
      possible effect, we have analyzed six autosomal polymorphic Alu loci from four
      different sites within the Spanish Basque region in order to ascertain any
      genetic heterogeneity among the Basques. The results are consistent with a lack
      of homogeneity among these four autochthonous Basque groups.

PMID- 11511930
TI  - A second case of somatic triple mosaicism in the CYBB gene causing chronic
      granulomatous disease.
AB  - The most common form of chronic granulomatous disease (CGD) is caused by
      mutations in the CYBB gene that is carried on the X-chromosome and give rise to
      the X-linked form of the disease. The product of this gene is the large subunit
      of flavocytochrome b558, gp91phox, the catalytic core of the superoxide
      generating enzyme, NADPH oxidase. In the overwhelming majority of cases,
      mutations are family-specific and occur in the exonic regions of the gene or,
      less frequently, at the intron/exon borders. In addition, there are large, often
      multi-gene, deletions. Four mutations have also been found in the promoter
      regions. In contrast, very few intronic mutations have been reported. Here we
      describe an unusual intronic mutation that causes CGD. The mutation is the
      insertion of 12 bp in intron XI, accompanied by the deletion of exon 12.
      Remarkably, the grandmother of this patient is chimeric, carrying a normal
      allele, the patient's allele, and an allele with a 4-nucleotide insertion at a
      site adjacent to the patient's insertion, in combination with a 1.5-kb deletion
      within intron XI. The patient's mother carries a normal allele and the patient's
      allele. We propose that an initial mutational event during the grandmother's
      embryogenesis has undergone unsuccessful DNA repair and has resulted in two
      aberrant alleles, one of which has been inherited by the patient and his mother.
      Remarkably, in the only two kindreds that have been examined in detail where
      deletions originating within introns have led to CGD, both families have
      contained members with triple somatic mosaicism.

PMID- 11511933
TI  - A surrogate for decision-making in the ICU.

PMID- 11511934
TI  - Mechanical circulatory support: expanding knowledge and experience in a
      challenging patient subset.

PMID- 11511935
TI  - Nosocomial infections during extracorporeal membrane oxygenation.
AB  - OBJECTIVE: To examine trends in nosocomial infection associated with
      Extracorporeal Membrane Oxygenation (ECMO). DESIGN: Retrospective review of all
      patients who underwent ECMO over a 4-year period at our institution;
      specifically, examining reasons for placement and duration of time on ECMO, as
      well as nosocomial infections incurred while on or shortly after discontinuation
      of support. Infections were considered ECMO-related if the organism was recovered
      on support or within 7 days from decannulation. Analyses were performed utilizing
      Pearson's chi-square for dichotomous factors and t-tests for continuous factors.
      RESULTS: Of 141 patients requiring ECMO support, 90 (64%) survived to hospital
      discharge. Indication for support included circulatory failure (53%) and non
      cardiac (47%). Twenty-six percent of patients developed infections on ECMO.
      Organisms isolated included: bacterial 20 (54%), fungal 10 (27%), mixed five
      (14%) and viral two (5%). Infection sites included: blood 13 (35%), urine nine
      (24%), mixed eight (22%), wound five (14%) and lung two (5%). Seventy-eight
      percent of infections noted occurred in cardiac patients. Patients with
      nosocomial infections were supported for a median of 169 h (range, 84-936 h),
      versus those without nosocomial infection [146 h (range, 50-886 h); P<0.001].
      Procedures on ECMO were associated with an increased risk of infection (P<0.001)
      as was the presence of an open chest (P<0.025). CONCLUSIONS: The incidence of
      infection in ECMO patients at our institution has not increased significantly
      since our previous study. Cardiac patients have increased risk for nosocomial
      infection while on ECMO, which may be in part due to longer cannulation times, as
      well as increased likelihood of undergoing major procedures or having an open
      chest.

PMID- 11511936
TI  - Comparison of different methodological approaches to identify risk factors of
      nosocomial infection in intensive care units.
AB  - OBJECTIVE: Comparison of statistical methods and measurement scales to identify
      nosocomial infection risk factors in intensive care units (ICU). DESIGN:
      Prospective study in 558 patients admitted to the ICU of a referral hospital
      between February and November 1994. METHODS: Analysis using three logistic
      regression models, three standard Cox regression models, and two Cox regression
      models with time-dependent extrinsic factors. Different scales were used to
      measure exposures to risk factors (dichotomous, ordinal, quantitative, and time
      dependent variables). RESULTS: The most appropriate models were those that
      measured exposure using dichotomous variables. Models using ordinal or
      quantitative variables estimated biased coefficients and/or failed to comply with
      the statistical assumptions underlying the analyses. The Cox regression model
      with quantitative time-dependent variables met all the statistical assumptions,
      obtained a precise assessment of risk by exposure time, and estimated unbiased
      coefficients. CONCLUSIONS: The Cox regression analysis with quantitative time
      dependent variables is the most valid alternative for assessing the risk of
      nosocomial infection per day of exposure to an extrinsic risk factor in the ICU.

PMID- 11511937
TI  - Endemicity, molecular diversity and colonisation routes of Pseudomonas aeruginosa
      in intensive care units.
AB  - OBJECTIVE: We carried out a prospective study to evaluate the endemicity of
      Pseudomonas aeruginosa in intensive care units (ICUs). Pulsed-field gel
      electrophoresis (PFGE) was used to determine the genotypes of P. aeruginosa
      isolates. This allowed us to determine the importance of cross-colonisation and
      the colonisation routes of P. aeruginosa. DESIGN: We screened epidemiological
      specimens (rectal swab, nose swab and tracheal aspiration) and routine clinical
      cultures from patients admitted to ICUs during a 2-year period, from 1st January,
      1998, to 31st December, 1999. SETTING: The study was carried out in four separate
      adult ICUs located in the Franche-Comte region of France. These four units
      admitted a total of 1,500 patients per year. RESULTS: A total of 1686 specimens
      were collected from 473 patients; 122 of these patients were positive on
      admission, 351 became positive during hospitalisation. The overall incidence of
      P. aeruginosa was 15.7 cases per 100 patients and 15.1 cases per 1000 days of
      hospitalisation. Of 184 patients with at least one ICU-acquired positive clinical
      culture, 104 had been previously identified as carriers by a similar genotype.
      Typing of 208 non-replicate isolates revealed 101 major DNA patterns.
      Approximately 50% of P. aeruginosa carriage or colonisation/infection was
      acquired via cross-transmission; the other cases probably originated from
      endogenous sources. CONCLUSION: Cross-colonisation seems to play an important
      role in the general spread of P. aeruginosa in ICUs.

PMID- 11511938
TI  - Detection of bacteraemia in critically ill patients using 16S rDNA polymerase
      chain reaction and DNA sequencing.
AB  - OBJECTIVE: To confirm the sensitivity of the polymerase chain reaction (PCR)
      technique (versus blood cultures) and to gain a better understanding of the
      incidence of true- and false-positive results when using this technique. DESIGN:
      Observational study. SETTING: Fourteen-bed, level 3 intensive care unit.
      PATIENTS: Hundred twenty-six critically ill adult patients. Hundred ninety-seven
      blood culture and PCR samples taken as clinically indicated for suspected sepsis,
      according to routine ICU protocol. MEASUREMENTS AND RESULTS: The PCR product
      (16SrDNA: 341F-1195R) was sequenced and compared with a database of known species
      (Genebank) to identify the bacterial nucleic acid. The PCR or blood culture
      result was classified as a true-positive if there was other microbiological or
      clinical supporting evidence.

PMID- 11511939
TI  - Extremely low doses of tissue factor pathway inhibitor decrease mortality in a
      rabbit model of septic shock.
AB  - OBJECTIVE: We sought to determine the lowest dose of recombinant human tissue
      factor pathway inhibitor (TFPI) that can provide protection from lethality in a
      rabbit model of septic shock. METHODS: Sepsis was induced in New Zealand white
      rabbits by intraperitoneal implantation of 7.0 ml of a solution containing
      hemoglobin (4.8 g/dl), porcine mucin (6 g/dl), and 0.8-1.4 x 10(4) viable
      Escherichia coli (strain O:18 K+). Gentamicin (5 mg/kg) was administered 4 h
      following surgery, and this dose was repeated every 12 h for 3 days. Beginning 4
      h following the induction of sepsis, animals were treated with a bolus (1 ml)
      plus a continuous infusion (100 ml over 24) of either TFPI (various doses) or its
      vehicle. Four different doses of TFPI were studied, and each experiment included
      a contemporaneous control group. The primary outcome parameter was survival time.
      Results were analyzed using the Wilcoxen log rank test. RESULTS: The average
      survival time for rabbits treated with the highest dose of TFPI tested (50
      microg/kg bolus and 0.5 microg/kg per minute infusion) was 118 h, as compared to
      81 h in vehicle-treated controls). The average survival time for septic rabbits
      treated with a much lower dose of TFPI (100 ng/kg bolus and 1.0 ng/kg per minute
      infusion) was 119 h as compared to 57 h in surviving vehicle-treated controls.
      Treatment with an even lower dose of TFPI (10 ng/kg bolus and 0.1 ng/kg per
      minute infusion) still produced a marginally significant prolongation of average
      survival time (80 h) relative to contemporaneously studied controls (47 h). When
      the dose of TFPI was decreased still further (1.0 ng/kg bolus and 0.01 ng/kg per
      minute infusion), average survival times were not significantly different between
      TFPI-treated and vehicle-treated rabbits (77 and 51 h, respectively).
      CONCLUSIONS: Delayed infusion with remarkably low doses of recombinant human TFPI
      prolongs survival in a rabbit model of antibiotic-treated Gram-negative bacterial
      sepsis. In planning human trials of TFPI as an adjuvant treatment for sepsis it
      may be reasonable to use much lower doses of the agent than were heretofore
      contemplated.

PMID- 11511940
TI  - Variability of splanchnic blood flow in patients with sepsis.
AB  - OBJECTIVES: Previous studies on therapeutic interventions in sepsis have assumed
      stability of the measure of splanchnic blood flow throughout the study. We
      assessed the variability of splanchnic blood flow during stable global
      hemodynamics in eight patients with sepsis requiring treatment with dobutamine
      and/or norepinephrine. DESIGN AND SETTING: Prospective clinical study in an
      intensive care unit of a university hospital. MEASUREMENTS AND RESULTS: Global
      and regional hemodynamics were measured at baseline, 2 h later, and 4 h later.
      Cardiac output was measured by transpulmonary thermodilution, intrathoracic blood
      volume as an indicator of cardiac preload, and total blood volume by the double
      indicator (thermo-dye) dilution technique. Total body oxygen consumption was
      assessed by indirect calorimetry using a metabolic cart. Splanchnic blood flow
      was measured by the continuous indocyanine green method, and gastric mucosal CO2
      tension by gas tonometry. Neither absolute nor fractional splanchnic blood flow
      (as ratio of cardiac output) revealed significant global tendencies during the
      study period. However, variance component analysis showed that splanchnic blood
      flow determinations varied considerably within patients, for repeated
      measurements at 5-min intervals (standard error 31.1%) as well as for average
      values at 2-h intervals (25.6%). CONCLUSION: Stable global hemodynamics during a
      4-h period in septic patients does not exclude marked changes in splanchnic blood
      measured by a hepatic venous catheter technique.

PMID- 11511941
TI  - Critical illness polyneuropathy: risk factors and clinical consequences. A cohort
      study in septic patients.
AB  - OBJECTIVE: To determine risk factors and clinical consequences of critical
      illness polyneuropathy (CIP) evaluated by the impact on duration of mechanical
      ventilation, length of stay and mortality. DESIGN: Inception cohort study.
      SETTING: Intensive care unit of a tertiary hospital. PATIENTS: Septic patients
      with multiple organ dysfunction syndrome requiring mechanical ventilation and
      without previous history of polyneuropathy. INTERVENTIONS: Patients underwent two
      scheduled electrophysiologic studies (EPS): on the 10th and 21st days after the
      onset of mechanical ventilation. RESULTS: Eighty-two patients were enrolled,
      although nine of them were not analyzed. Forty-six of the 73 patients presented
      CIP on the first EPS and 4 other subjects were diagnosed with CIP on the second
      evaluation. The APACHE II scores of patients with and without CIP were similar on
      admission and on the day of the first EPS. However, days of mechanical
      ventilation [32.3 (21.1) versus 18.5 (5.8); p=0.002], length of ICU and hospital
      stay in patients discharged alive from the ICU as well as in-hospital mortality
      were greater in patients with CIP (42/50, 84% versus 13/23, 56.5%; p=0.01). After
      multivariate analysis, independent risk factors were hyperosmolality [odds ratio
      (OR) 4.8; 95% confidence intervals (95% CI) 1.05-24.38; p=0.046], parenteral
      nutrition (OR 5.11; 95% CI 1.14-22.88; p=0.02), use of neuromuscular blocking
      agents (OR 16.32; 95% CI 1.34-199; p=0.0008) and neurologic failure (GCS below
      10) (OR 24.02; 95% CI 3.68-156.7; p<0.001), while patients with renal replacement
      therapy had a lower risk for CIP development (OR 0.02; 95% CI 0.05-0.15;
      p<0.001). By multivariate analysis, CIP (OR 7.11; 95% CI 1.54-32.75; p<0.007),
      age over 60 years (OR 9.07; 95% CI 2.02-40.68; p<0.002) and the worst renal SOFA
      (OR 2.18; 95% CI 1.27-3.74; p<0.002) were independent predictors of in-hospital
      mortality. CONCLUSIONS: CIP is associated with increased duration of mechanical
      ventilation and in-hospital mortality. Hyperosmolality, parenteral nutrition, non
      depolarizing neuromuscular blockers and neurologic failure can favor CIP
      development.

PMID- 11511942
TI  - Delirium in an intensive care unit: a study of risk factors.
AB  - OBJECTIVES: (1) To establish risk factors for the development of delirium in an
      intensive care unit (ICU) and (2) to determine the effect of delirium on
      morbidity, mortality and length of stay. DESIGN: Prospective study. SETTING:
      Sixteen-bed medical/surgical ICU in a university hospital. PATIENTS: Two hundred
      and sixteen consecutive patients admitted to the ICU for more than 24 h during 5
      months were included in the study. INTERVENTIONS: Medical history, selected
      laboratory values, drugs received and factors that may influence patient
      psychological and emotional well-being were noted. All patients were screened
      with a delirium scale. A psychiatrist confirmed the diagnosis of delirium. Major
      complications such as self-extubation and removal of catheters, as well as
      mortality and length of stay were recorded. RESULTS: Forty patients (19%)
      developed delirium; of these, one-third were not agitated. In the multivariate
      analysis hypertension, smoking history, abnormal bilirubin level, epidural use
      and morphine were statistically significantly associated with delirium.
      Traditional factors associated with the development of delirium on general ward
      patients were not significant in our study. Morbidity (self-extubation and
      removal of catheters), but not mortality, was clearly increased. CONCLUSION:
      Predictive risk factors for the development of delirium in studies outside the
      ICU may not be applicable to critically ill patients. Delirium is associated with
      increased morbidity. Awareness of patients at risk may lead to better recognition
      and earlier intervention.

PMID- 11511943
TI  - Time-dependency of sensory evoked potentials in comatose cardiac arrest
      survivors.
AB  - OBJECTIVE: To assess the validity of early sensory evoked potential (SEP)
      recording for reliable outcome prediction in comatose cardiac arrest survivors
      within 48 h after restoration of spontaneous circulation (ROSC). DESIGN AND
      SETTING: Prospective cohort study in a medical intensive care unit of a
      university hospital. PATIENTS: Twenty-five comatose, mechanically ventilated
      patients following cardiopulmonary resuscitation MEASUREMENTS AND RESULTS: Median
      nerve short- and long-latency SEP were recorded 4, 12, 24, and 48 h after ROSC.
      Cortical N20 peak latency and cervicomedullary conduction time decreased
      (improved) significantly between 4, 12, and 24 h after resuscitation in 22 of the
      enrolled patients. There was no further change in short-latency SEP at 48 h. The
      cortical N70 peak was initially detectable in seven patients. The number of
      patients with increased N70 peak increased to 11 at 12 h and 14 at 24 h; there
      was no further change at 48 h. Specificity of the N70 peak latency (critical
      cutoff 130 ms) increased from 0.43 at 4 h to 1.0 at 24 h after ROSC. Sensitivity
      decreased from 1.0 at 4 h to 0.83 at 24 h after ROSC. CONCLUSION: Within 24 h
      after ROSC there was a significant improvement in SEP. Therefore we recommend
      allowing a period of at least 24 h after cardiopulmonary resuscitation for
      obtaining a reliable prognosis based on SEP.

PMID- 11511944
TI  - Detection of flow limitation in mechanically ventilated patients.
AB  - OBJECTIVE: In mechanically ventilated patients flow limitation often goes
      unrecognised. We compared three methods for detection of flow limitation in
      mechanically ventilated patients: the resistance method, the negative expiratory
      pressure (NEP) method, and the interrupter method. DESIGN: Prospective study.
      SETTING: A medical intensive care unit in a university hospital. PATIENTS: Twenty
      six patients (20 COPD, six other pathology), mechanically ventilated under
      sedation. MEASUREMENTS AND RESULTS: Respiratory mechanics were obtained during
      application of the three methods. For the resistance method, flow limitation was
      expressed as percentage of expiratory tidal volume, in which flow did not
      decrease (FLP-R). For the NEP method, flow limitation was expressed as percentage
      of expiratory tidal volume in which flow did not increase (FLP-NEP). For the
      interrupter method, flow limitation was expressed as area of spike-overshoot in
      flow after interruption. In 18 COPD patients, flow limitation was detected by all
      methods; mean FLP-R 76% (SD 12%), mean FLP-NEP 90% (SD 11%), mean spike area 21
      ml (SD 7 ml). In three patients with other pathology, these values were,
      respectively, 20% (SD 19%), 48% (SD 21%), and 5 ml (SD 4 ml). The three methods
      were in close agreement. In nine patients the resistance method increased flow
      and in six patients the NEP method decreased flow compared to the unimpeded
      breath. CONCLUSIONS: In mechanically ventilated patients, flow limitation can
      well be detected by the resistance-, NEP-, and interrupter methods. However, the
      NEP method can overestimate the flow limited portion, while the resistance method
      can underestimate the flow limited portion. The interrupter method is found to be
      less practical.

PMID- 11511945
TI  - Differential indication for mechanical circulatory support following heart
      transplantation.
AB  - PURPOSE: We describe our experience with ventricular assist devices (VAD) in
      patients with cardiogenic shock refractory to pharmacological therapy and support
      using intraaortic balloon pump after cardiac transplantation. PATIENTS: Between
      July 1987 and August 1997, 848 patients underwent cardiac transplantation in our
      hospital. INTERVENTIONS: Fifteen patients (1.8%) needed mechanical circulatory
      support for refractory cardiac failure due to right heart failure (six patients),
      primary graft failure (three patients), and acute rejection (six patients). Three
      pump systems were used: Biomedicus Centrifugal Pump, Abiomed BVS 500, and
      Thoratec VAD. The choice of system depended on the indication and quality of each
      device. Seven patients (47%) could be weaned from the mechanical circulatory
      support (MCS) system and three patients (20%) are long-term survivors. RESULTS:
      All 15 patients developed at least one serious complication, such as multiorgan
      failure (MOF), liver failure, acute renal failure or sepsis. Twenty-five per cent
      had severe bleeding and 13% had neurological complication. Mortality was due
      mostly to MOF, MOF and sepsis or sepsis. The survivors had a CI greater than 2.2
      l.min.m2, total bilirubin less than 1.0 U/1, and did not undergo resuscitation.
      CONCLUSIONS: Heart failure after cardiac transplantation severe enough to require
      MCS is currently associated with several major complications and high mortality
      (80%).

PMID- 11511946
TI  - Continuous on-line measurements of respiratory system, lung and chest wall
      mechanics during mechanic ventilation.
AB  - OBJECTIVE: We present a concept of on-line, manoeuvre-free monitoring of
      respiratory mechanics during dynamic conditions, displaying calculated alveolar
      pressure/volume curves continuously and separating lung and chest wall mechanics.
      DESIGN: Prospective observational study. SETTING: Intensive care unit of a
      university hospital. PATIENTS: Ten ventilator-treated patients with acute lung
      injury. INTERVENTIONS: Different positive end-expiratory pressure (PEEP) and
      tidal volumes, low flow inflation. MEASUREMENTS AND RESULTS: Previously validated
      methods were used to present a single-value dynostatic compliance for the whole
      breath and a dynostatic volume-dependent initial, middle and final compliance
      within the breath. A high individual variation of respiratory mechanics was
      observed. Reproducibility of repeated measurements was satisfactory (coefficients
      of variations for dynostatic volume-dependent compliance: < or =9.2% for total
      respiratory system, < or =18% for lung). Volume-dependent compliance showed a
      statistically significant pattern of successively decreasing compliance from the
      initial segment through the middle and final parts within each breath at all
      respiratory settings. This pattern became more prominent with increasing PEEP and
      tidal volume, indicating a greater distension of alveoli. No lower inflection
      point (LIP) was seen in patients with respiratory rate 20/min and PEEP at 4
      cmH2O. A trial with low flow inflation in four of the patients showed formation
      of a LIP in three of them and an upper inflection in one. CONCLUSIONS: The
      monitoring concept revealed a constant pattern of successively decreasing
      compliance within each breath, which became more prominent with increasing PEEP
      and tidal volume. The monitoring concept offers a simple and reliable method of
      monitoring respiratory mechanics during ongoing ventilator treatment.

PMID- 11511947
TI  - Total extracorporeal arteriovenous carbon dioxide removal in acute respiratory
      failure: a phase I clinical study.
AB  - OBJECTIVE: To evaluate the safety and efficacy of pumpless extracorporeal
      arteriovenous carbon dioxide removal (AVCO2R) in subjects with acute respiratory
      failure and hypercapnia. DESIGN: A phase I within-group time series trial in
      which subjects underwent up to 72 h of support with AVCO2R in intensive care
      units of two university hospitals. PATIENTS: Eight patients with acute
      hypercapnic respiratory failure or hypoxemic respiratory failure managed with
      permissive hypercapnia. INTERVENTIONS: Extracorporeal CO2 removal was achieved
      through percutaneous cannulation of the femoral artery and vein, and a simple
      extracorporeal circuit using a commercially available membrane gas exchange
      device for carbon dioxide exchange. MEASUREMENTS AND RESULTS: Measurements of
      hemodynamics, blood gases, ventilatory settings, and laboratory values were made
      before initiation of AVCO2R, and at subsequent intervals for 72 h. PaCO2
      decreased significantly from 90.8+/-7.5 mmHg to 52.3+/-4.3 and 51.8+/-3.1 mmHg at
      1 and 2 h, respectively. This decrease occurred despite a decrease in minute
      ventilation from a baseline of 6.92+/-1.64 l/min to 4.22+/-.46 and 3.00+/-.53
      l/min at 1 and 2 h. There was a normalization of pH, with an increase from 7.19+/
      .06 to 7.35+/-.07 and 7.37+/-.05 at 1 and 2 h. These improvements persisted
      during the full period of support with AVCO2R. Four subjects underwent apnea
      trials in which AVCO2R provided total carbon dioxide removal during apneic
      oxygenation, resulting in steady-state PaCO2 values from 57 to 85 mmHg.
      Hemodynamics were not significantly altered with the institution of AVCO2R. There
      were no major complications attributed to the procedure. CONCLUSION: Pumpless
      extracorporeal AVCO2R is capable of providing complete extracorporeal removal of
      carbon dioxide during acute respiratory failure, while maintaining mild to
      moderate hypercapnia. Applied in conjunction with mechanical ventilation and
      permissive hypercapnia, AVCO2R resulted in normalization of arterial PCO2 and pH
      and permitted significant reductions in the level of mechanical ventilation.

PMID- 11511948
TI  - The oxygenation variations related to prone positioning during mechanical
      ventilation: a clinical comparison between ARDS and non-ARDS hypoxemic patients.
AB  - OBJECTIVES: To compare, in clinical practice, the oxygenation variations related
      to prone positioning (PP) during mechanical ventilation in ARDS and non-ARDS
      hypoxemic patients. DESIGN AND SETTING: Prospective observational study of data
      on consecutive patients treated with the same protocol in the intensive care unit
      (ICU) of a university hospital. PATIENTS: From May 1996 to December 1998, 226 PP
      periods without adjunction of nitric oxide (NO) inhalation and/or almitrine
      bismesylate infusion, performed in 59 mechanically ventilated hypoxemic patients
      (arterial oxygen tension/fractional inspired oxygen (PaO2/FIO2) ratio <300 mmHg)
      with no evidence of left ventricular failure, were included in this study.
      MEASUREMENTS: Arterial blood gas was measured before the PP, at 1 h from the
      beginning of the PP, at the end of the PP and 1 h after returning to the supine
      position. RESULTS: We analyzed 136 PP periods in 34 non-ARDS patients (60.2%) and
      90 in 25 ARDS patients. The PP was repeated and the duration of the PP periods
      was: 10.6+/-0.22 h. The PP during the mechanical ventilation appeared to be safe
      and well tolerated. A PaO2/FIO2 ratio improvement at the end of the PP period,
      occurred for 196 periods (86.7%) with a mean PaO2/FIO2 ratio increase of +46.4+/
      0.03% at the end of the PP periods compared to the baseline supine value. The
      PaO2/FIO2 ratio variations at 1 h after the start of the PP, at the end of the PP
      period and at 1 h after the return to supine were not different in ARDS or non
      ARDS hypoxemic patients. The PaO2/FIO2 ratio improvement appeared to be more
      intense and more rapid in ARDS patients. CONCLUSIONS: In about 90% of periods, PP
      improved the PaO2/FIO2 ratio in patients with ARDS as well as in hypoxemic
      patients with non-ARDS. Studies are necessary to determine the impact of PP on
      survival and the mechanical ventilation duration in ARDS or non-ARDS hypoxemic
      patients.

PMID- 11511949
TI  - Decision-making capacity and surrogate designation in French ICU patients.
AB  - OBJECTIVE: To evaluate the capacity and willingness of French-speaking patients
      to designate a surrogate within 24 h of their ICU admission. French laws fail to
      indicate what should be done when an otherwise legally competent patient
      transiently loses his decision-making capacity. DESIGN: Surrogate designation was
      prospectively evaluated during two study periods. Only conscious patients were
      assessed using the Glasgow Come Score in the first study period, and all admitted
      patients were assessed in the second period. Decision-making capacity was
      evaluated using the Mini Mental Status Examination (MMSE) in the second study
      period. SETTING: Twenty six-bed intensive care unit (ICU) in a French teaching
      hospital. PATIENTS AND PARTICIPANTS: Over a 8-month period 495 patients were
      included in the study, 415 in the first study period and 80 in the second.
      MEASUREMENTS AND RESULTS: Of the 495 patients 185 (37.3%) were interviewed, and
      62.7% designated a surrogate. The surrogate was the spouse in 50% of cases and a
      child in 28.4%. Only 25.8% were considered to have decision-making capacity;
      78.1% of competent patients and 28% of the patients without decision-making
      capacity agreed to designate a surrogate. CONCLUSIONS: Surrogate designation by a
      patient should be evaluated in the light of the decision-making capacity of the
      patient. The traditional French paternalism still practiced by many French
      physicians appears out of tune with the wishes of their patients. We suggest that
      there is a need for developing a simple and effective tool for assessing decision
      making capacity in ICU patients.

PMID- 11511950
TI  - Inter-observer variability in APACHE II scoring: effect of strict guidelines and
      training.
AB  - OBJECTIVE: To assess the effect of strict guidelines and a rigorous training
      program on variability in scoring the revised Acute Physiology and Chronic Health
      Evaluation (APACHE II). DESIGN AND SETTING: Prospective survey and intervention
      in the surgical ICU of a university teaching hospital. MEASUREMENTS: Seven
      experienced intensivists and nine residents determined APACHE II scores in one
      set of patients before and in another set 4 months after a rigorous training
      program, following strict guidelines for using the APACHE II. RESULTS: APACHE II
      scores were 14.3+/-4.4 before the training program (n=12) and 18.9+/-2.4 after
      (n=11). Interobserver agreement rates increased significantly from 59.7% to 76.5%
      and the interobserver reliability coefficient (weighted kappa) from 0.72 to 0.85
      after our training program was implemented. The changes were significantly
      greater in experienced intensivists than in less experienced residents,
      indicating that more experienced physicians profited to a greater degree from our
      training program. CONCLUSION: Interobserver variability in APACHE II scoring
      decreases markedly when strict guidelines and a regular training program are
      implemented, particularly among more experienced physicians. However, in our
      study a degree of variability (10-15%) persisted even in experienced intensivists
      with similar training, experience, and background, suggesting that a degree of
      variability is inherent in APACHE II scoring.

PMID- 11511951
TI  - Treatment of acute methanol poisoning with fomepizole.
AB  - OBJECTIVE: To assess the efficacy and safety of fomepizole, a competitive alcohol
      dehydrogenase inhibitor, in methanol poisoning and to test the hypothesis that
      fomepizole obviates the need for hemodialysis in selected patients. DESIGN AND
      SETTING: Retrospective clinical study in three intensive care units in university
      affiliated teaching hospitals. PATIENTS: All methanol-poisoned patients admitted
      to these ICUs and treated with fomepizole from 1987-1999 (n=14). MEASUREMENTS AND
      RESULTS: The median plasma methanol concentration was 50 mg/dl (range 4-146),
      anion gap 22.1 mmol/l (11.8-42.2), arterial pH 7.34 (7.11-7.51), and bicarbonate
      17.5 mmol/l (3.0-25.0). Patients received oral or intravenous fomepizole until
      blood methanol was undetectable. The median cumulative dose was 1250 mg (500
      6000); the median number of twice daily doses was 2 (1-16). Four patients
      underwent hemodialysis for visual impairment present on admission. Four patients
      with plasma methanol concentrations of 50 mg/dl or higher and treated without
      hemodialysis recovered fully. Patients without pretreatment visual disturbances
      recovered, with no sequelae in any case. There were no deaths. Fomepizole was
      safe and well tolerated, even in the case of prolonged treatment. Analysis of
      methanol toxicokinetics in five patients demonstrated that fomepizole was
      effective in blocking methanol's toxic metabolism. CONCLUSIONS: Fomepizole
      appears safe and effective in the treatment of methanol-poisoned patients. If our
      results are confirmed in prospective analyses, hemodialysis may prove unnecessary
      in patients presenting without visual impairment or severe acidosis.

PMID- 11511952
TI  - Release of interleukin-10 by reinfusion of salvaged blood after knee
      arthroplasty.
AB  - OBJECTIVES: To determine whether the method of the autotransfusion in association
      with knee arthroplasty leads to differences in anti-inflammatory cytokines in the
      patient's circulation. DESIGN AND SETTING: Prospective study in a university
      hospital. PATIENTS: Twenty-one patients undergoing knee arthroplasty were
      randomized into two groups assigned to postoperative blood salvage. Seven
      patients received postoperatively filtered salvaged blood, and seven received
      centrifuged and washed salvaged blood. Patients with postoperative blood loss
      less than 400 ml (n=7) did not receive any transfusion. MEASUREMENTS AND RESULTS:
      Plasma levels of interleukin (IL) 1beta, IL-4, and IL-10 and of polymorphonuclear
      leukocyte elastase were measured by enzyme-linked immunosorbent assay. The plasma
      concentration of IL-10 was elevated after reinfusion of salvaged blood in all
      groups 1 day after surgery (p<0.05). Plasma IL-6, IL-10, and PMN elastase was
      higher (p<0.01) in all groups 1 day after surgery than preoperatively. There were
      significantly higher plasma levels 1 min after retransfusion of IL-6 (p<0.01) and
      IL-10 (p<0.05) in patients receiving filtered blood than in those receiving
      centrifuged and washed salvaged blood. CONCLUSION: Total knee arthroplasty
      results in the release of interleukin-10. Transfusion of filtered salvaged blood
      leads to higher levels of cytokines IL-6 and IL-10 than after transfusion of
      washed and centrifuged salvaged blood.

PMID- 11511953
TI  - Non-invasive radiation-free monitoring of regional lung ventilation in critically
      ill infants.
AB  - OBJECTIVE: Established techniques used to examine lung function in critically ill
      infants cannot continuously follow regional aspects of lung ventilation although
      this information would be beneficial for proper therapy planning. We have studied
      the applicability and clinical relevance of a relatively new non-invasive
      radiation-free imaging method, electrical impedance tomography (EIT), in
      monitoring regional lung function in paediatric intensive care patients. DESIGN:
      Prospective study. SETTING: Neonatal and paediatric intensive care unit (ICU) at
      a university hospital. PATIENTS: Eight infants (1 day-7 years old) suffering from
      miscellaneous diseases requiring intensive care therapy. INTERVENTIONS:
      Adjustment of ventilator settings, surfactant administration, and postural
      changes. MEASUREMENTS AND RESULTS: Repeated EIT measurements were performed with
      the intention to monitor regional lung ventilation in mechanically ventilated and
      spontaneously breathing infants. The follow-up time ranged between 1 and 11 days.
      During individual EIT measurements of 100-s duration electrical voltages
      resulting from repetitive injection of small electrical currents were
      continuously measured on the thoracic circumference using conventional surface
      electrodes. Acquired data were used to generate functional cross-sectional
      thoracic images of regional lung ventilation. A total of 638 EIT measurements
      were performed. The redistribution of lung ventilation and changes in regional
      ventilation magnitude resulting from adjusted positive end-expiratory pressure,
      peak inspiratory pressure, inspiration-expiration ratio, surfactant instillation,
      and prone or supine positioning were identified. CONCLUSIONS: Provided that EIT
      hardware and software are further developed to guarantee stable and undisturbed
      measurements in the ICU and that practical handling is improved, this non
      invasive method may become a useful bedside monitoring tool of regional lung
      ventilation in critically ill infants.

PMID- 11511954
TI  - Coagulation factor activity during neonatal extra-corporeal membrane oxygenation.
AB  - OBJECTIVE: To ascertain the activity of major coagulation factors during the
      first 24 h of extra-corporeal membrane oxygenation (ECMO) used to support
      hypoxaemic neonates. DESIGN AND SETTING: A prospective observational study in a
      regional centre for ECMO and paediatric cardiac surgery, placing 15-20 neonates
      on ECMO per year. PATIENTS: Ten neonates receiving ECMO for severe hypoxaemia.
      MEASUREMENT AND RESULTS: The activity of major clotting factors, of the inhibitor
      anti-thrombin III and of markers of blood activation were measured during the
      first 24 h of neonatal extra-corporeal membrane oxygenation (ECMO) and prior to
      initiation of ECMO. There was laboratory evidence of factor deficiency and of
      activation of coagulation at all stages. The initiation of ECMO leads to an
      initial worsening of coagulopathy, but factor deficiency and abnormal activation
      of coagulation is also seen prior to ECMO in these very sick neonates.
      CONCLUSION: If factor deficiency is to be avoided a pro-active approach is
      required to rapidly correct factor activity. This would include the use of fresh
      frozen plasma. The effect of such an approach on outcome is at yet uncertain.

PMID- 11511955
TI  - Cerebro-splanchnic oxygenation ratio (CSOR) using near infrared spectroscopy may
      be able to predict splanchnic ischaemia in neonates.
AB  - OBJECTIVE: To investigate whether near infrared spectroscopy (NIRS) can detect
      differences in oxyhaemoglobin signal when applied to the abdomens of neonates
      with surgically proven splanchnic ischaemia. DESIGN: Prospective, observational
      cohort study. SETTING: Tertiary neonatal referral centre. PATIENTS: Medical and
      surgical neonates were studied. Two groups were identified, neonates with acute
      abdomens referred for surgery and those with normal abdomens admitted for medical
      reasons. INTERVENTIONS: Tissue oxygenation indexes (TOI) of cerebral and
      splanchnic regions were measured using near infrared spectroscopy (NIRS) and
      their relative values expressed as a cerebro-splanchnic oxygenation ratio (CSOR).
      Measurements were made on admission or immediately prior to surgery and
      subsequently repeated on a daily basis, whenever possible, until discharge from
      our unit. The area under the receiver operating characteristic (ROC) curve was
      evaluated and optimum diagnostic cut-off values determined. RESULTS: Forty
      neonates were studied: 10 with acute abdomens, including four with necrotising
      enterocolitis (NEC), 29 controls with normal abdomens and one with cerebral
      hypoxic ischaemic injury. Median CSOR for the control group was 0.96
      (interquartile range 0.83-1.02) whereas the acute abdomen group had a
      significantly lower median CSOR value of 0.66 (0.45-0.69) (p<0.001). The area
      under the ROC was 0.91 (95% confidence limits 0.78-1.00) for CSOR. Taking a
      boundary value of CSOR for the prediction of splanchnic ischaemia as less than
      0.75, intestinal ischaemia was identified with a positive predictive value of
      0.75 (0.43-0.95) and excluded with a negative predictive value of 0.96 (0.81
      1.0). This was a better performance than using abdominal TOI alone. CONCLUSIONS:
      By comparing the TOI of cerebral and splanchnic regions it may be possible to
      establish the presence of normal splanchnic perfusion and detect when splanchnic
      ischaemia develops. CSOR had a 90% (56-100%) sensitivity to detect splanchnic
      ischaemia in neonates. Further work is necessary to confirm these early findings
      and establish whether abdominal NIRS has a clinical role in detecting splanchnic
      ischaemia.

PMID- 11511956
TI  - Transient mesenteric ischaemic episodes tracked by continuous jejunal PCO2
      monitoring during liquid feeding.
AB  - OBJECTIVE: To test the effect of liquid feeds on the responses to splanchnic
      ischaemia of a continuous rapid response PCO2 sensor inserted in the jejunum.
      DESIGN: Prospective experimental animal study in a university research
      laboratory. SUBJECTS: Adult male Wistar rats. INTERVENTIONS: Adult male Wistar
      rats (285-425 g) were anaesthetised with sodium pentobarbitone 60 mg/kg i.p. and
      ventilated with 100% oxygen and isoflurane via tracheostomy to a PaCO2 of 30-40
      mmHg. A sensor was inserted into the mid-jejunum to record PCO2 every second.
      Distal aortic pressure was transduced. Four control rats received no feeds whilst
      in another four rats liquid feed was infused into the proximal jejunum at 3 ml/h.
      In each rat five episodes of splanchnic ischaemia were induced by 2-min
      elevations of an aortic sling to a mean distal aortic pressure of 30 mmHg.
      MEASUREMENTS AND MAIN RESULTS: PCO2 elevations were always detectable, usually
      less than a minute from the onset of splanchnic ischaemia in both fed and unfed
      rats, with no difference in mean times to detectable response. In the fed rats
      there was a small but significant increase in the time to peak sensor response
      (196+/-16 vs. 180+/-12 s) and a trend towards an elevated mean baseline luminal
      PCO2 (67+/-9 vs. 55+/-4 mmHg). CONCLUSIONS: Brief episodes of splanchnic
      ischaemia were tracked successfully by a rapid response jejunal continuous PCO2
      sensor during the infusion of a proprietary liquid feed preparation despite minor
      changes in PCO2 response characteristics and a possible elevation in baseline
      luminal PCO2.

PMID- 11511957
TI  - Plasma levels of macrophage migration inhibitory factor are elevated in patients
      with severe sepsis.
AB  - OBJECTIVE: To investigate the role of macrophage migration inhibitory factor
      (MIF) as a marker of severity of systemic inflammation in patients with severe
      sepsis and critically ill postsurgical patients. DESIGN: Prospective
      observational study in consecutive patients with severe sepsis, critically ill
      nonseptic postsurgical patients, and healthy blood donors. SETTING: A surgical
      intensive care unit of a university hospital. PATIENTS AND PARTICIPANTS: 19
      patients with severe sepsis, 18 critically ill nonseptic postsurgical patients,
      and 10 healthy blood donors. MEASUREMENTS AND RESULTS: MIF plasma levels of
      patients and participants were measured. Interleukin 6 plasma levels were
      monitored as a control marker of inflammation. The median MIF plasma level was
      four to five times higher in patients with severe sepsis (2.70 ng/ml, range 0.31
      19.59) and in critically ill nonseptic postsurgical patients (2.43 ng/ml, range
      0.49-4.31) than in healthy blood donors (0.56 ng/ml, range 0.16-1.68). MIF plasma
      levels did not differ between the patient groups. CONCLUSIONS: MIF serves as a
      general marker for systemic inflammation in septic and nonseptic acute critical
      illness, but MIF does not discriminate for severity or differentiate between
      infectious and noninfectious origins of an acute critical illness.

PMID- 11511958
TI  - The effects of vasopressin on hemodynamics and renal function in severe septic
      shock: a case series.
AB  - OBJECTIVE: To review all cases of septic shock treated with vasopressin to
      determine the effects on hemodynamic and renal function and to document any
      adverse effects. SETTING: A 14-bed mixed medical-surgical ICU of St. Paul's
      Hospital, a 450-bed tertiary referral hospital affiliated with the University of
      British Columbia. PATIENTS: All ICU patients who received vasopressin for
      treatment of severe septic shock between August 5, 1997, and March 21, 1999.
      RESULTS: We identified 50 patients: age 60 (+/-14); APACHE II score 27 (+/-7).
      Baseline data (T0) was compared to data at T4, T24 and T48 (4, 24 and 48 h) on
      infusion. Mean arterial pressure (MAP) increased by 18% from T0 to T4 and
      remained stable at T24 (p=0.006) and T48 (p=0.008). Systolic pulmonary artery
      pressure (PAP) was unchanged at 45+/-13 mmHg. Mean cardiac index (CI) decreased
      by 11% at T4 (p=0.03). Urine output increased 79% at T4 (p=0.005) and further
      increases were not significant at T24 and T48. Mean pressor dosage decreased by
      33% at T4 (p=0.001), by 53% at T24 (p=0.002) and by 48% at T48 (p=0.01). Hospital
      mortality was 85%. There were six cardiac arrests; all but one occurred at a
      vasopressin dose of 0.05 U/min or more. CONCLUSIONS: In this group of patients
      with severe septic shock, vasopressin infusion increased MAP and urine output and
      decreased catecholamine requirements. Doses higher than 0.04 U/min were not
      associated with increased effectiveness and may have been associated with higher
      adverse effects.

PMID- 11511959
TI  - Non-occlusive small bowel necrosis during gastric tube feeding: a case report.
AB  - Small bowel necrosis is known as a rare, but serious complication of jejunal tube
      feeding. We report a case of non-occlusive small bowel necrosis with gastric tube
      feeding. The patient had a moderate multiple trauma with head injury. Abdominal
      distension developed after several days of uneventful nasogastric tube feeding.
      At laparotomy patchy necrosis of the small bowel was found without signs of bowel
      obstruction or impaired mesenteric perfusion. The patient recovered after a
      prolonged ICU stay. In this case the large doses of clonidine, given due to an
      alcohol withdrawal syndrome, were suspected to be a major contributing factor to
      the development of the small bowel necrosis by impairing gut motility and mucosal
      perfusion. We conclude that, first, small bowel necrosis can occur after
      primarily uneventful enteral feeding, even with gastric feeding; second,
      clonidine can dramatically impair gastrointestinal function in critically ill
      patients by impairing gut motility and mucosal perfusion.

PMID- 11511960
TI  - Craniectomy in severe, life-threatening encephalitis: a report on outcome and
      long-term prognosis of four cases.
AB  - OBJECTIVE: To report the feasibility of craniectomy with duraplasty in four
      patients with life-threatening encephalitis and, in particular, their long-term
      outcome. DESIGN: Report of four cases, analysis of the acute clinical course and
      neurological long-term sequelae. RESULTS: Generous craniectomy with duraplasty
      was performed in four patients with life-threatening encephalitis leading to
      decortication and decerebration. This treatment approach reduced intracranial
      pressure. The long-term sequelae (1.5-8 years after craniectomy) confirmed its
      appropriateness, having led to full neurological (cerebral) function,
      resocialization, and reintegration into their professional life in all four
      patients. CONCLUSION: Craniectomy with dural augmentation is a treatment approach
      in cases of severe space-occupying encephalitis, not only saving the patient's
      life but also leading to favorable long-term outcome.

PMID- 11511961
TI  - Management of peripartum cardiomyopathy.

PMID- 11511962
TI  - Thrombolysis and cardiopulmonary resuscitation: two techniques that are not
      necessarily opposed.

PMID- 11511963
TI  - Prepartum cardiomyopathy requires a specific management.

PMID- 11511964
TI  - Simultaneous EEG and ECG recording of sinus arrest.

PMID- 11511965
TI  - Intravenous amiodarone in intensive care: time for a reappraisal?

PMID- 11511966
TI  - Adrenal insufficiency in critically ill.

PMID- 11511967
TI  - Bilateral breast necrosis after prone position ventilation.

PMID- 11511968
TI  - Antibiotic use in pediatric intensive care patients with lower respiratory tract
      infection due to respiratory syncytial virus.

PMID- 11511969
TI  - Bleeding complications associated with thrombolytic therapy in out-of-hospital
      cardiac arrest.

PMID- 11511970
TI  - Insecticides and atherosclerosis.

PMID- 11511971
TI  - JMM, past and present. Cysticerci cellulosae of the brain. 1864.
AB  - While striving to serve the needs of the international biomedical community of
      today, we would also like to remember JMM's long past as a venue for medical
      research. JMM is the successor to the Berlin Clinical Weekly (Berliner Klinische
      Wochenschrift), established in 1864. Below are excerpts from the Berlin Clinical
      Weekly's May issue from a hundred and thirty-five years ago, giving hints about
      the challenges and solutions being addressed by medical research of the time.
      Following the excerpt is a commentary by Martin Zeitz and Thomas Schneider,
      experts in gastroenterology at the University Clinic Benjamin Franklin in Berlin,
      Germany.

PMID- 11511972
TI  - CD3+CD4-CD8- alphabeta-TCR+ T cell as immune regulatory cell.
AB  - Down-regulation of immune responses by regulatory T cells is one of the major
      mechanisms involved in the induction of tolerance to self- and alloantigens as
      demonstrated in a number of models of transplantation and autoimmunity. It is
      clear that regulatory T cells consist of different subsets. Recently a novel
      subset of antigen-specific alphabeta-TCR+ CD4-CD8- (double negative, DN)
      regulatory T cells has been found to be able to inhibit the function of the CD8+
      T cells carrying the same T cell receptor specificity and prevent the rejection
      of skin allografts. Identification of the DN regulatory T cells and their novel
      mechanism of suppression can help us to understand how donor-specific
      transplantation tolerance can be achieved and to explain how tolerance to self
      antigens can be maintained in the periphery.

PMID- 11511973
TI  - Aggressive childhood neuroblastomas do not express caspase-8: an important
      component of programmed cell death.
AB  - Neuroblastomas that overexpress N-Myc due to amplification of the MYCN oncogene
      are aggressive tumors that become very resistant to treatment by chemotherapy and
      irradiation. to identify tumor suppressor genes in this group of neuroblastomas
      we analyzed the expression and function of both apoptosis-related cell cycle
      regulatory genes in cell lines and patient tumor samples. We found that in a high
      percentage of neuroblastoma cell lines and patient samples with amplified MYCN,
      caspase-8 mRNA is not expressed. The caspase-8 gene, CASP8, was deleted or
      silenced by methylation in the neuroblastoma cell lines while methylation of its
      promoter region was the predominant mechanism for its inactivation in the patient
      tumor samples. Reintroduction of caspase-8 into the neuroblastoma cell lines
      resensitized these cells to drug-induced and survival factor dependent apoptosis.
      Subsequently others have also shown that caspase-8 is silenced by methylation in
      neuroblastoma and peripheral neural ectodermal tumors, and that the caspase-9
      regulator Apaf-1 is silenced by methylation in melanoma cell lines and patient
      samples. We conclude that caspase-8 acts as a tumor suppressor gene in
      neuroblastomas, that its silencing provides a permissive environment for MYCN
      gene amplification once the tumors are treated with chemotherapeutic
      drugs/irradiation, and that expression of this gene in these tumor cells may be
      of clinical benefit. We also discuss the possible significance of the neural
      crest cell progenitor cell origin and the silencing of important apoptotic
      regulators via methylation in both neuroblastoma and melanoma tumors.

PMID- 11511974
TI  - Diabetic endothelial dysfunction: role of reactive oxygen and nitrogen species
      production and poly(ADP-ribose) polymerase activation.
AB  - Peroxynitrite and hydroxyl radicals are potent initiators of DNA single-strand
      breakage, which is an obligatory stimulus for the activation of the nuclear
      enzyme poly(ADP ribose) polymerase (PARP). In response to high glucose incubation
      medium in vitro, or diabetes and hyperglycemia in vivo, reactive nitrogen and
      oxygen species generation occurs. These reactive species trigger DNA single
      strand breakage, which induces rapid activation of PARP. PARP in turn depletes
      the intracellular concentration of its substrate, NAD+, slowing the rate of
      glycolysis, electron transport, and ATP formation. This process results in acute
      endothelial dysfunction in diabetic blood vessels. Accordingly, inhibitors of
      PARP protect against endothelial injury under these conditions. In addition to
      the direct cytotoxic pathway regulated by DNA injury and PARP activation, PARP
      also appears to modulate the course of inflammation by regulating the activation
      of nuclear factor kappaB, and the expression of a number of genes, including the
      gene for intercellular adhesion molecule 1 and the inducible nitric oxide
      synthase. The research into the role of PARP in diabetic vascular injury is now
      supported by novel tools, such as new classes of potent inhibitors of PARP and
      genetically engineered animals lacking the gene for PARP. Pharmacological
      inhibition of PARP emerges as a potential approach for the experimental therapy
      of diabetic vascular dysfunction.

PMID- 11511975
TI  - Paraoxonase gene polymorphisms and coronary reactivity in young healthy men.
AB  - This study examined the relationships between paraoxonase genotypes, coronary
      artery reactivity, and indices of low-density lipoprotein oxidation in healthy
      men. Impairment in coronary flow reserve, as assessed by positron emission
      tomography, is associated with lipoprotein oxidation, which is affected by high
      density lipoprotein bound enzyme, paraoxonase. Paraoxonase has two common
      polymorphisms (M/L55 and R/Q192) that change the activity of the enzyme. Forty
      nine healthy men (mean age 35 +/- 4 years) were divided by paraoxonase genotype
      into low (Q192/Q192, or M55/M55, M55/L55) and high-active (R192/Q192, R192/R192,
      or L55/L55) groups and related to the myocardial blood flow, to the
      susceptibility of low-density lipoprotein to oxidation, and the autoantibody
      titer against oxidized low-density lipoprotein. The blood flow was measured by
      positron emission tomography at rest and during adenosine infusion. The low
      active Q192/Q192 genotype was associated with higher resting blood flow corrected
      for rate-pressure product compared to the high-active R192/R192 and R192/Q192
      genotypes (P=0.011). The blood flow stimulated by adenosine was not significantly
      different in the low- and high-active genotype groups. Paraoxonase genotypes had
      no effect on low-density lipoprotein susceptibility to oxidation or autoantibody
      formation against oxidized low-density lipoprotein. Genotypes of paraoxonase may
      not clearly contribute to the early changes in coronary reactivity. Coronary
      vasomotor tone at rest appears to be modulated by paraoxonase R/Q192 polymorphism
      through mechanism(s) unrelated to low-density lipoprotein oxidation.

PMID- 11511976
TI  - Paraoxonase promoter polymorphism T(-107)C and relative paraoxonase deficiency as
      determinants of risk of coronary artery disease.
AB  - This study tested the hypothesis that promoter polymorphism T(-107)C of the human
      paraoxonase gene (PON1) is associated with risk of coronary disease. Participants
      (n=897) were recruited from a cardiology department. All underwent coronary
      arteriography and were defined as coronary artery disease positive (n=699) or
      negative (n=198). No association of the promoter genotypes with coronary disease
      was observed in the overall population, but the high expressor genotype (-107CC)
      was associated with decreased risk of disease in patients aged 60 years or under
      in univariate and multivariate analysis independently of established risk
      factors. A significant deficiency in paraoxonase relative to cholesterol was
      apparent in patients, even when they were matched with controls for total and low
      density lipoprotein cholesterol levels. The -107 polymorphism was not associated
      with risk in older patients (61 years or over). Age was negatively associated
      with serum concentrations and activities of paraoxonase; serum paraoxonase was
      significantly higher in those aged under 61 years than in those aged 61 or over.
      Age was an independent predictor of paraoxonase concentrations. The results
      indicate that in this population of patients the promoter polymorphism T(-107)C
      of the PON1 gene is an independent risk factor for coronary disease in those 60
      years or younger. The data are consistent with the hypothesis that lower
      expression of this anti-oxidant enzyme increases risk of coronary disease. Ageing
      has also been identified as an independent determinant of serum paraoxonase
      levels. Ageing is correlated with reduced serum paraoxonase levels, which may
      compromise the protective influence of enzyme. The results are consistent with
      the contention that the protective, anti-oxidant capacity of high density
      lipoproteins is at least in part genetically determined.

PMID- 11511978
TI  - Basiliximab induction improves the outcome of renal transplants in children and
      adolescents.
AB  - Thirty-two children and adolescents received their renal transplant at the
      Montefiore Medical Center, in New York, between October 1996 and May 2000. Twenty
      four patients received basiliximab, in addition to tacrolimus and steroids
      (basiliximab group). The remaining eight patients received only tacrolimus and
      steroids (non-basiliximab group). The 1-year patient survival rate was 100% in
      both groups. The 1-year graft survival rate was 87.5% for the basiliximab group
      and 75% for the non-basiliximab group (P=0.45). The rates of acute rejection in
      the basiliximab and non-basiliximab groups were 26% and 43%, respectively
      (P=0.36). However, in recipients with <or=3 HLA mismatches, the rate of acute
      rejection was zero in the basiliximab group, and 40% in the non-basiliximab group
      (P=0.04). The beneficial effect occurred despite the fact that tacrolimus was
      maintained at below the target levels. There were no adverse events directly
      attributable to the administration of basiliximab. There were no cases of
      opportunistic infections or post-transplant lymphoproliferative disease. In
      summary, addition of basiliximab to tacrolimus and prednisone significantly
      decreased the rate of acute rejection in well-matched patients. Moreover, this
      effect was manifest at lower, and therefore less toxic, tacrolimus levels.

PMID- 11511977
TI  - Transdifferentiation of polymorphonuclear neutrophils: acquisition of CD83 and
      other functional characteristics of dendritic cells.
AB  - Polymorphonuclear neutrophils (PMN) are in the first line of defense against
      bacterial infections. They are considered to be end-differentiated cells
      undergoing constitutive apoptosis within hours after release from the bone
      marrow. During pathological events, however, their life span is extended in
      conjunction with morphological and functional alterations indicative of a
      transdifferentiation of mature PMN. To further characterize differentiated PMN,
      the alterations seen in vivo were reproduced by cultivating PMN of healthy donors
      with either gamma-interferon, granulocyte/macrophage colony stimulating factor,
      or a combination thereof. Thus cultivated cells escaped from apoptosis, and
      protein synthesis was induced, notably of the major histocompatibility complex
      (MHC) class II antigens, CD80 and CD86. Moreover, CD83, thought to be specific
      for dendritic cells was synthesized, while typical markers of PMN, including
      CD66b, CD11a/CD11b/CD11c, CD15, CD18 were preserved. A profound alteration of
      both cellular morphology and of function was seen: the cultivated PMN lost their
      chemotactic activity but had acquired the ability to present to T-cells a peptide
      antigen in a MHC class II restricted manner. The data lead to the conclusion that
      mature PMN can differentiate further to cells with characteristics of DCs,
      thereby connecting PMN to the specific T-cell response.

PMID- 11511979
TI  - Acute peritoneal dialysis as both cause and treatment of hypernatremia in an
      infant.
AB  - This report describes a 4-month-old infant with multisystem organ failure who
      developed severe hypernatremia (sodium 168 mEq/l) due to rapid free water removal
      associated with acute peritoneal dialysis instituted for fluid overload. The
      current report describes the pathophysiology of the hypernatremia, and its
      correction by low-sodium hypertonic peritoneal dialysis without compromising
      ultrafiltration or supplementing with free water. Although peritoneal dialysis
      can cause hypernatremia, a modified solute concentration in the dialysate can
      treat the hypernatremia successfully.

PMID- 11511981
TI  - Hsal 1 is related to kidney and gonad development and is expressed in Wilms
      tumor.
AB  - Townes-Brocks syndrome (TBS) is a human genetic disorder with features including
      urogenital, limb, anal and cardiac malformations associated with mutations of the
      TBS gene, Hsal 1. To begin to understand the role of the Hsal 1 protein (p140) in
      both normal development and disease pathogenesis, both message and protein
      expression were evaluated in specific tissues associated with TBS. DNA sequence
      information for Hsal 1 predicts that this homeotic, Drosophila homologue (Sal)
      encodes a zinc-finger protein consistent with a transcription factor. mRNA for
      Hsal 1 was highly expressed in fetal kidney and brain, with detectable production
      in thymus and heart. p140 was found in fetal ureteric bud, fetal and postnatal
      renal tubular epithelium, and renal blastema. In the 14-week fetal testis, the
      Hsal 1 protein was specifically expressed in the testosterone producing Leydig
      cells while in adult gonads Hsal 1 was also found in both Leydig and Sertoli
      cells, spermatogonia of the testis, and granulosa cells of the ovary. Evaluation
      of Wilms tumor revealed consistently high expression of the gene product in the
      epithelial and blastemal components. These spatial and temporal patterns of
      expression for Hsal 1, and the phenotypic effects associated with TBS, suggest
      that Hsal 1 plays an important role in the development and functional maintenance
      of the kidney and gonads. Furthermore, the Hsal 1 gene product may play a part in
      the pathogenesis of specific neoplasms occurring in these organs in addition to
      its specific role in Townes-Brocks syndrome.

PMID- 11511982
TI  - Mitochondrial tubulopathy: the many faces of mitochondrial disorders.
AB  - We report a rare presentation of mitochondrial disorder in a child with recurrent
      carpopedal spasms due to hypocalcemia and hypomagnesemia, secondary to renal
      proximal tubulopathy and possible hypoparathyroidism. At least two mutant
      mitochondrial DNA species were identified, and abnormal mitochondria were found
      in the muscle and renal biopsy specimens. The case illustrates the spectrum and
      diversity of mitochondrial presentations, arising because of heteroplasmy of
      mutations and the type of organs affected.

PMID- 11511984
TI  - The renal hemodynamic effects of Aspirin in newborn and young adult rabbits.
AB  - A group of neonatal (n=10) and 12-week-old (n=12) anesthetized, ventilated New
      Zealand white rabbits received an acute i.v. dose (40 mg/kg body weight) of
      acetylsalicylic acid (ASA, Aspirin). In the neonatal animals, i.v. ASA caused
      within 20 min a significant (P<0.01) fall in renal blood flow and glomerular
      filtration rate (GFR), with an equally significant (P<0.01) increase in
      filtration fraction and renal vascular resistance. The latter indicates greatly
      augmented renal vasconstriction or more precisely reduction in intrarenal
      vasodilatation by inhibition of vasodilatory prostaglandin (PG) synthesis. Urine
      volume decreased. The 12-week-old young adult animals responded in a similar, but
      significantly attenuated fashion. These experiments demonstrate that inhibition
      of PG synthesis in neonatal animals causes very rapid, reversible
      vasoconstriction, with a reduction in GFR. In addition, this study confirms
      previous observations that the renal hemodynamic response to the inhibition of PG
      synthesis is far more pronounced in neonatal animals than in (young) adult
      rabbits.

PMID- 11511985
TI  - Tubular urinary enzymes in acute post-infectious glomerulonephritis.
AB  - Tubular function of 17 pediatric patients with a mild form of acute post
      infectious glomerulonephritis was prospectively evaluated by assessment of the
      urinary activity of proximal and distal tubule enzymes. Neutral-like
      endopeptidase (NEP-like) and angiotensin-converting enzyme (ACE) were the
      proximal tubule enzymes assessed, while prolyl-endopeptidase (PE) and serine
      endopeptidase H1 and H2 were the distal tubule enzymes analyzed. Urine was
      collected at diagnosis (T0) and after 2 (T2) and 6 (T6) months of follow-up. NEP
      like enzyme activity (nmol/mg creatinine; median+/-quartile range) was increased
      at diagnosis, and this remained stable during the first 6 months (T0 18.30+/
      83.26, T2 17.32+/-49.56, T6 23.38+/-107.18). Urinary activity of the other
      enzymes was as follows: ACE (mU/ml per mg creatinine) T0 0.08+/-0.16, T2 0.06+/
      0.10, T6 0.18+/-0.29; PE (nmol/mg creatinine) T0 6.70+/-84.87, T2 9.55+/-69.00,
      T6 13.67+/-28.70; serine-endopeptidase H1 (nmol/mg creatinine) T0 7.86+/-26.95,
      T2 17.17+/-59.37, T6 18.19+/- 79.14; and serine-thiol-endopeptidase H2 (nmol/mg
      creatinine) T0 3.06+/-21.97, T2 12.06+/-32.42, T6 16.22+/- 44.06. Thirty other
      healthy children matched for age and gender were considered as a control group.
      This group was assessed once and the results were: NEP-like activity 6.05+/
      10.54, ACE 0.11+/-0.22, PE 7.10+/-13.36, H1 5.00+/-17.30, and H2 6.00+/-20.16. In
      conclusion, we observed that NEP-like and H1 enzymes exhibited significant
      increased urinary activity 6 months after the diagnosis. This increase occurred
      in spite of the disappearance of clinical symptoms, which occurred 2 months after
      the diagnosis. We believe that the increase in urinary enzymatic activity could
      be a manifestation of a silent tubular dysfunction following an episode of acute
      post-infectious glomerulonephritis.

PMID- 11511986
TI  - Recovery from cyclosporine-associated arteriolopathy in childhood nephrotic
      syndrome.
AB  - Cyclosporine (CS) is well recognized to be effective in the treatment of children
      with steroid-dependent and steroid-resistant nephrotic syndrome (NS), but its use
      can result in chronic nephrotoxicity. The histological changes that occur after
      CS discontinuation are unknown. Therefore, we examined the histological changes
      [CS-associated arteriolopathy (CAA), tubulointerstitial lesions, and focal
      glomerular lesions] in renal biopsy specimens after the drug had been
      discontinued in eight children with idiopathic nephrotic syndrome (NS). These
      children had been treated with long-term moderate-dose CS and had shown mild-to
      moderate chronic CS nephrotoxicity. The degree of CAA improved significantly
      after CS discontinuation (mean CAA grade from 1.30+/-0.46 to 0.25+/-0.46,
      P=0.028). CAA disappeared in six of these children after CS discontinuation.
      However, the tubulointerstitial lesions and the focal glomerular lesions did not
      change after CS discontinuation. In conclusion, in children with idiopathic NS,
      CAA is improved by discontinuation of CS, but tubulointerstitial changes and
      focal glomerular lesions do not regress with drug discontinuation.

PMID- 11511987
TI  - Pediatric urolithiasis in Armenia: a study of 198 patients observed from 1991 to
      1999.
AB  - To study prospectively the risk factors and etiology of urolithiasis in all stone
      patients aged <15 years admitted from 1991 to 1999 to the Arabkir hospital in
      Yerevan. Stones were obtained by surgery (64%), extracorporeal shockwave
      lithotripsy (ESWL) (7%) or cystoscopic extraction (4%); 25% passed spontaneously.
      All were examined by infrared spectroscopy, and spot urines were analyzed
      chemically. 198 patients, 180 (68% males) with renal stones and 18 (83% males)
      with primary bladder stones, were studied. Calcium oxalate (CaOx) was the
      predominant constituent in 62% of the kidney stones, followed by struvite (17%),
      calcium phosphate (7%), uric acid (7%), ammonium acid urate (5%), and cystine
      (2%). Bladder stones contained CaOx in 72%, uric acid in 22% and ammonium acid
      urate in 6% of patients. Etiology was obviously metabolic in 5% and possibly
      metabolic in 26%. Twenty percent of stones were infectious, and 19% were endemic
      (9% bladder and 10% kidney stones); 4% were secondary to urinary stasis with
      malformation but no infection. Etiology in 26% remained unknown. Stone
      composition and metabolic etiology are similar to that in central Europe and
      North America. In contrast, infectious calculi and particularly endemic stones
      are still common, although becoming less so now. Urolithiasis in Armenia thus
      reflects the transition from a rural to an urban society.

PMID- 11511988
TI  - Acute renal cortical scintigraphy in children with a first urinary tract
      infection.
AB  - This prospective study, performed in 101 children with a first symptomatic
      urinary tract infection (UTI), evaluates the diagnostic value of clinical,
      biological, and ultrasound parameters in detecting children with acute renal
      infection documented by dimercaptosuccinic acid (DMSA) scintigraphy. In children
      with a positive DMSA scan, mean C-reactive protein (CRP) was higher than in
      children with a normal DMSA scan (114+/-64 vs. 67+/-38 mg/dl, mean+/-SD,
      P=0.0002). The sensitivity and specificity of CRP was 64% and 68%, respectively.
      In children with severe kidney involvement, mean CRP and white blood count (WBC)
      were higher than in children with mild/moderate disease (151+/-83 vs. 92+/-55
      mg/dl for CRP, P=0.0149; 20,100+/-6,854 vs. 15,023+/-6,145 WBC/ mm3 for WBC,
      P=0.0131). The sensitivity and specificity was 85% and 20% for CRP, and 77% and
      18% for WBC, respectively. One or more areas of abnormal cortical echogenicity
      were documented in 3% of kidneys with positive DMSA scans. Dilatation of the
      collecting system was observed in 24% of kidneys. The sensitivity and specificity
      of ultrasonography was 27% and 89%, respectively. In conclusion, clinical,
      biological, and ultrasound parameters do not accurately distinguish cystitis from
      pyelonephritis in children with UTI and do not identify children with severe
      renal damage. Accordingly, we recommend that DMSA scan should be added to the
      initial work-up of children with UTI.

PMID- 11511989
TI  - Abundance and activity of Ca2+-ATPase in hypercalciuric children.
AB  - The plasma membrane Ca2+-ATPase (PMCA) is one of the main regulators of cell Ca2+
      homeostasis. The aim of our study was to determine whether the abundance and
      activity of PMCA are altered in erythrocytes of children with idiopathic
      hypercalciuria. Twenty-four children with idiopathic hypercalciuria (13 girls and
      11 boys, mean age 10.6+/-4.8 years; mean urinary calcium concentration 0.85+/
      0.20 mmol/mmol creatinine) and 30 healthy age-matched children were enrolled.
      PMCA protein abundance was determined by Western blot analysis. Enzyme activity
      was determined spectrophotometrically. The abundance of PMCA did not differ in
      hypercalciuric patients from that of control subjects (98+/-22% vs 100+/-18%).
      Moreover, the activity was not different between the studied groups (3141+/-1494
      vs 2953+/-780 nmol ATP/mg protein/h). The extent of hypercalciuria did not
      correlate with enzyme abundance or activity. Assuming that erythrocytes may
      reflect the renal tubular transporting processes, our data suggest that other
      Ca2+-transport mechanisms than PMCA might be involved in the development of
      idiopathic hypercalciuria in children.

PMID- 11511991
TI  - Acute reversible renal failure with macroscopic hematuria in Henoch-Schonlein
      purpura.
AB  - A Japanese girl aged 5 years 4 months developed macroscopic hematuria and acute
      renal failure (ARF) 8 days before the appearance of purpura rash. A renal biopsy
      undertaken during the acute phase of illness revealed many red blood cells in the
      tubular lumina with no apparent glomerular lesions. ARF showed improvement
      without dialysis therapy. A second renal biopsy was performed 2.5 months later
      because of the prolonged proteinuria and hematuria. Sclerotic change and crescent
      formation were demonstrated in 30% and 20% of glomeruli, respectively. Red blood
      cell casts in the tubular lumina were completely resolved. It is likely that the
      tubular change was involved in the development of ARF at the onset of illness.
      Although ARF during or after episodes of macroscopic hematuria has been observed
      in IgA nephropathy, it may occur as an uncommon complication in Henoch-Schonlein
      nephritis, which is a common glomerulonephritis in children.

PMID- 11511993
TI  - Nutcracker phenomenon demonstrated by three-dimensional computed tomography.
AB  - We report a 15-year-old girl with nutcracker syndrome (NCP) in whom three
      dimensional helical computed tomography (3D helical CT) was useful for diagnosis;
      angiographic imaging using 3D helical CT provided fine outlines of the vascular
      structures in NCP, i.e., a compression of the left renal vein between the aorta
      and the superior mesenteric artery and the abnormal acute angle between them.
      Thus, a 3D helical CT enables precise depiction of the anatomical characteristics
      of renal vasculature and, therefore, may be a useful alternative imaging
      technique instead of conventional examinations, such as invasive venography or
      digital subtraction angiography. Further study in a large number of children with
      vascular abnormalities would be worthwhile.

PMID- 11511994
TI  - Familial hypercalcemia and hypercalciuria: no mutations in the Ca2+-sensing
      receptor gene.
AB  - A 6-year-old boy presented with persistent hypercalcemia, hypercalciuria and
      nephrocalcinosis from early infancy. His 40-year-old father also had
      hypercalcemia and hypercalciuria. In both individuals serum values of intact
      parathyroid hormone (PTH) were repeatedly normal. Although these findings suggest
      a functional abnormality of the calcium-sensing receptor (CaR), no mutations in
      coding regions of the CaR gene could be demonstrated.

PMID- 11511995
TI  - Update on endothelins - biology and clinical implications.
AB  - In the decade since the initial discovery and characterization of endothelin, its
      biology as a powerful vasoconstrictor has been dramatically demonstrated. Studies
      have clarified the existence of endothelin isoforms, complex mechanisms of
      biosynthesis, interaction with specific receptors, and pathogenic implications.
      We are on the brink of using endothelin antagonism as a clinical treatment for
      disease processes where endothelin plays an important role, including congestive
      heart failure and hypertension. Novel observations have been made about the
      unexpectedly profound contribution endothelins make to normal fetal maturation,
      especially in cardiac and enteric development.

PMID- 11511996
TI  - Ontogeny of renal phosphate transport and the process of growth.
AB  - The kidneys of infants and children reabsorb a high fraction of the filtered
      phosphate (Pi), as appropriate to the needs of a growing organism. This high Pi
      reabsorptive rate is associated with a high capacity (Vmax) of the Na+-Pi symport
      system. At the molecular level this high reabsorptive capacity appears to be due
      to the presence of a growth-specific Na-Pi cotransporter. Several experimental
      findings support this assumption. Firstly, the expression of NaPi-2 mRNA is, if
      anything, lower in the renal cortex of young animals than of adult animals.
      Secondly, polyA RNA obtained from growing animals depleted of NaPi-2 by specific
      hybridization with an antisense 16-mer induces Na+-Pi transport in oocytes. No
      induction of Na+-Pi transport was observed in oocytes injected with hybridized
      polyA RNA obtained from adult animals. Thirdly, polyA RNA derived from young
      rats, depleted of NaPi-2 by subtractive hybridization with adult animal renal
      cortical cDNA, retains its ability to encode for Na+-Pi cotransport in oocytes.
      Adult animal renal cortical polyA RNA, depleted of NaPi-2 by subtractive
      hybridization, failed to induce Na+-Pi uptake into oocytes. Fourthly, renal
      cortical polyA RNA from young animals, depleted of NaPi-2, contains a region that
      is highly homologous (80%-92%) with the corresponding region of other modulated
      NaPi (type II) transporters. Fifthly, this region is also present in the polyA
      RNA obtained from the renal cortex of newborn rats (1st week of life), despite
      the fact that NaPi-2 is absent at this early age. Lastly, Npt2 (-/-) knockout
      mice, although hypophosphatemic and phosphaturic, filter and reabsorb Pi at rates
      exceeding those that can be accounted for by the expression of type I and III
      transporters. Based on these observations it is reasonable to surmise that the
      high Vmax of the Na+-Pi cotransport system observed in the young is due to a
      large extent to the presence of a growth-specific NaPi transporter, homologous
      but not identical to already cloned type II NaPi transporters.

PMID- 11511997
TI  - Radiation-induced meningioma with a long latency period: a case report.
AB  - Multiple meningiomas were diagnosed in a 43-year-old man previously treated with
      high-dose craniospinal radiotherapy at the age of 7 years for medulloblastoma. We
      suggest that surveillance MRI after high-dose craniospinal radiotherapy should be
      extended to several (3-5) decades.

PMID- 11511998
TI  - Intracranial cavernous hemangioma in a neonate.
AB  - Cogenital intracranial hemangioma is rare, and the imaging findings have been
      described in very few cases. We describe a case of a huge congenital left
      parietal hemangioma that was diagnosed postnatally by head duplex
      ultrasonography. Complete surgical resection yielded an excellent outcome.

PMID- 11511999
TI  - Pontoneocerebellar hypoplasia: definition of MR features.
AB  - We report five patients with pontoneocerebellar hypoplasia. Because the issue of
      cerebellar malformations is a difficult subject, we tried to define criteria for
      diagnosis on MRI: a thin flat pons with disappearance of the anterior curve, a
      small cerebellum with predominant flattening of the hemispheres and shortened
      cerebellar fissures, in contrast to atrophy. The posterior fossa is not enlarged.
      We emphasize the probable late onset of the disease in fetal life because of the
      demonstration of the abnormalities at US during the last trimester of the
      pregnancy in one patient. Prenatal diagnosis is important because of possible
      autosomal recessive transmission.

PMID- 11512001
TI  - Magnetic resonance imaging in the diagnosis and management of choroid plexus
      carcinoma in children.
AB  - BACKGROUND: Choroid plexus carcinoma (CPC) is a rare tumour occurring in
      childhood. The MRI features are not well described. OBJECTIVE: To characterise
      the MRI features of CPC in children and to describe the role of MRI in post
      surgical management. MATERIALS AND METHODS: The pre- and post-operative MRI
      examinations of five children with histologically proven CPC treated at this
      hospital were reviewed. RESULTS: The tumour was supratentorial in two patients
      and infratentorial in three patients. Pre-operative MRI showed heterogeneous
      enhancing tumours with irregular margins, parenchymal invasion and surrounding
      oedema. Cystic change within the tumour was present in all patients. Curvilinear
      signal voids were seen in two patients and punctate signal voids in one. All
      patients had hydrocephalus. In one patient a fourth-ventricular metastasis was
      present at diagnosis. In all cases, surgical resection was incomplete. Follow-up
      found long-term survival in one patient who had been treated with chemotherapy
      and further surgery. CONCLUSION: The MRI characteristics of CPC are nonspecific,
      but intraventricular location with tumour heterogeneity, parenchymal invasion and
      oedema may be useful features in diagnosis. MRI is valuable in the initial
      diagnosis, surgical planning and follow-up of children with these rare tumours.

PMID- 11512000
TI  - Herpes simplex encephalitis: MRI findings in two cases confirmed by polymerase
      chain reaction assay.
AB  - Herpes simplex virus (HSV) type I causes a fulminant necrotising
      meningoencephalitis distinguished from other encephalitides by its focal and
      often haemorrhagic nature. Specific antiviral therapy with acyclovir can
      significantly improve the prognosis. We present MRI findings of two cases of
      herpes simplex encephalitis (HSE) confirmed by PCR analysis, focusing on the
      serial changes after acyclovir therapy: gyral swelling, high signal intensity on
      T2-weighted images in the subfrontal region, temporal lobe and insula in the
      initial stage, then regional extension with enhancement and haemorrhage despite
      appropriate acyclovir therapy, and finally encephalomalacia and brain atrophy.

PMID- 11512002
TI  - Imaging features of primary malignant rhabdoid tumour of the brain.
AB  - Primary malignant rhabdoid tumour of the central nervous system is a rare
      neoplasm affecting children. We present a pathologically proven case, which was
      initially referred to the paediatric surgeons as a sebaceous cyst, and highlights
      the importance of imaging prior to surgery of potentially innocuous scalp
      lesions. Imaging features on CT and MRI are presented, which show bony
      involvement not previously reported in the literature.

PMID- 11512003
TI  - Ultrasound diagnosis of the anterior urethral valve.
AB  - We present a neonate with an obstructing anterior urethral valve depicted by
      longitudinal transpenile ultrasound. Voiding images are recommended to identify
      the obstructing valve tissue. Ultrasound depiction of the anterior urethral valve
      tissue is identical to that seen in posterior urethral valves.

PMID- 11512004
TI  - Klippel-Feil syndrome with cervical diastematomyelia in an 8-year-old boy.

PMID- 11512005
TI  - Diffuse, retroperitoneal mesenteric and intrahepatic periportal plexiform
      neurofibroma in a 5-year-old boy.
AB  - We present a case of plexiform neurofibroma involving the retroperitoneum,
      mesentery, and liver in a 5-year-old boy who underwent evaluation for extent of a
      palpable left neck mass. The mass had intrathoracic extension with great vessel
      encasement and extension into the abdomen. Abdominal CT revealed a diffuse low
      attenuation non-enhancing mass encasing the retroperitoneal vessels with
      serpiginous extension into the liver along the portal vein. This spread pattern
      of plexiform neurofibroma is an unusual manifestation of neurofibromatosis in a
      young child.

PMID- 11512006
TI  - The AP diameter of the pelvis: a new criterion for continence in the exstrophy
      complex?
AB  - OBJECTIVE: Reconstructive surgery of bladder exstrophy remains a challenge. By
      using CT of the pelvis, we suggest a new pre- and post-operative investigative
      procedure to define the AP diameter (APD) as a predictive criterion for
      continence in this anomaly. PATIENTS AND METHODS: Three axial CT slices were
      selected in nine children with exstrophy who had undergone neonatal
      reconstructive surgery. The three levels selected were the first sacral plate,
      the mid acetabular plane and the superior pubic spine. We used combined slices to
      measure: APD = distance between the first sacral vertebra and the pubic
      symphysis. Pubic diastasis (PD). Three angles defined on the transverse plane of
      the first sacral vertebra--iliac wing angle, sacropubic angle and acetabular
      version. RESULTS: In exstrophy, the angles demonstrate opening of the iliac wings
      and the pubic ramus, and acetabular retroversion compared to controls.
      Comparisons between controls, continent and incontinent patients reveal that in
      continent patients, APD increases with growth and seems to be a predictive
      criterion for continence, independent of diastasis of the pubic symphysis.
      CONCLUSIONS: We believe that CT of the pelvis with measurements of the APD should
      be performed in all neonates with bladder exstrophy before reconstructive surgery
      and for better understanding of the malformation. The APD seems to be predictive
      and may be a major criterion for continence, independent of PD.

PMID- 11512007
TI  - Paediatric pelvic imaging: improvement in gonad shield placement by
      multidisciplinary audit.
AB  - BACKGROUND: In 1996, there were local reports of poor gonad protection for
      paediatric pelvic radiographs. OBJECTIVES: To investigate the nature of the
      problem and make necessary improvements. MATERIALS AND METHODS: A retrospective
      audit of 218 paediatric pelvic radiographs was undertaken in 1997. Each
      radiograph was assessed for the presence of a gonad shield, appropriateness of
      the device and its position. A multidisciplinary team was formed with
      representation from radiology, radiography, orthopaedics and medical physics to
      investigate ways of improving technique and reducing patient dose. These included
      radiographer training and the introduction of digital fluoroscopy as an
      alternative imaging technique in follow-up patients. There were further rounds of
      data collection in 1998 and 1999. RESULTS: In round 1, a gonad shield was present
      in 77.9 % of boys' films and 76 % of girls' films where one should have been,
      increasing to 85.2 % and 85.4 % respectively by round 3 of the audit (P < 0.05).
      Only 31.6 % of boys' devices and 21.9 % of girls' devices were correctly
      positioned in round 1, increasing to 78.3 % and 94.3 %, respectively, by round 3
      of the audit (P < 0.05). After round 1, no inappropriate devices were used.
      CONCLUSION: Audit was an effective tool in gaining the resources needed to
      improve technique and reduce radiation exposure in children. The
      multidisciplinary approach was vital in the success of this project.

PMID- 11512008
TI  - Pancreatic arterial calcium stimulation in the diagnosis and localisation of
      persistent hyperinsulinemic hypoglycaemia of infancy.
AB  - BACKGROUND: Persistent hyperinsulinemic hypoglycaemia of infancy (PHHI) is often
      resistant to medical therapy. Surgery is therefore necessary. It is due to focal
      adenomatous islet-cell hyperplasia treatable by partial pancreatectomy, or
      diffuse beta-cell hyperfunction, which requires near-total pancreatectomy.
      Pancreatic venous sampling (PVS) is the reference technique for the preoperative
      diagnosis and localization of focal forms of PHHI in the pancreas. However,
      hypoglycaemia is necessary to analyse the results and PVS is technically
      challenging. Pancreatic arterial calcium stimulation (PACS) is technically easier
      and does not require hypoglycaemia. AIM: To study the accuracy in the diagnosis
      and localization of PHHI. MATERIALS AND METHODS: PACS was performed in 12
      patients and correlated with histology. RESULTS: The accuracy of PACS is poor in
      diffuse lesions since only two of six cases were correctly identified by this
      test. Five of six focal lesions were correctly recognized and located.
      CONCLUSIONS: PACS is less accurate than PVS in PHHI. Currently, it should be
      performed only when PVS fails.

PMID- 11512009
TI  - Gastric pneumatosis associated with duodenal stenosis and malrotation.
AB  - Pneumatosis intestinalis, which is linear or cystic gas within the bowel wall, is
      usually found in premature babies in association with necrotizing enterocolitis.
      Gastric pneumatosis defined as intramural gas of the stomach is a rare sign
      during infancy. We report an infant with Down's syndrome and a duodenal web with
      obvious gastric pneumatosis.

PMID- 11512010
TI  - Severe cervical kyphosis in osteopathia striata with cranial sclerosis: case
      report.
AB  - We report a 29-month-old girl with osteopathia striata with cranial sclerosis (OS
      CS), who showed several unusual manifestations, including short stature, muscular
      hypotonia, short lingual frenulum, an accessory ear and a granuloma at the oral
      edge. The most unusual distressing finding was severe cervical kyphosis with a
      dysplastic cervical spine. MRI revealed impingement of the upper spinal cord. To
      clarify the mode of inheritance of this disease in this patient, we performed a
      methylation-specific PCR analysis. It eventually showed random inactivation of X
      chromosomes, suggesting an autosomal dominant trait.

PMID- 11512011
TI  - Neonatal lethal dwarfism with distinct skeletal malformations--a separate entity?
AB  - We describe a case of neonatal lethal dwarfism characterised by short trunk,
      short, stick-like tubular bones, deficient ossification of the axial skeleton and
      broad, sclerotic horizontal ribs. Two similar cases have previously been reported
      as examples of the Neu-Laxova syndrome. However, the radiological findings of the
      Neu-Laxova syndrome, as reported in 16 out of 40 documented cases, show a
      heterogeneous pattern of minor features, which differ distinctively from those
      found in the previous two cases and by us. A literature research did not reveal
      similar cases, and we therefore suggest that our case, together with the two
      previous cases, may represent a new distinctive form of neonatal lethal dwarfism.

PMID- 11512012
TI  - Low-intensity fetal lungs on MRI may suggest the diagnosis of pulmonary
      hypoplasia.
AB  - BACKGROUND: Pulmonary hypoplasia is a common cause of neonatal death. Despite the
      recent advances in prenatal diagnosis with US, the diagnosis of pulmonary
      hypoplasia is difficult. The recent application of fast MR imaging may provide
      additional valuable information. OBJECTIVE: To evaluate pulmonary hypoplasia in
      the fetus with MRI. MATERIALS AND METHODS: The subjects comprised 23 fetuses (18
      40 weeks' gestation), including major anomalies diagnosed on fetal
      ultrasonography (n = 20), maternal abnormality (n = 2) and one normal twin. MRI
      was performed with a 1.5-T magnet and half-Fourier acquisition single-shot turbo
      spin-echo (HASTE) sequences. MR images were interpreted by three radiologists
      with special attention to the intensity of the lungs. The lung-to-liver intensity
      ratio was calculated by means of region-of-interest (ROI) analysis. The diagnosis
      of pulmonary hypoplasia depended on clinical, surgical and autopsy findings.
      RESULTS: All fetuses with normal pulmonary development showed high intensity in
      the lung except for one fetus at 24 weeks' gestational age. All fetuses with
      pulmonary hypoplasia showed lung of low intensity. CONCLUSIONS: Low-intensity
      fetal lung on MRI imaging indicates pulmonary hypoplasia after 26 weeks'
      gestation.

PMID- 11512013
TI  - Hypoxic/ischemic etiologic factors in the development of infants with sonographic
      lenticulostriate vasculopathy.

PMID- 11512014
TI  - Ascending aortic aneurysm in a boy with vasculitis.

PMID- 11512015
TI  - Testicular microlithiasis associated with congenital urethroperineal fistula.

PMID- 11512016
TI  - CT findings in hyperacute non-accidental brain injury.

PMID- 11512018
TI  - The physiology of immune evasion during pregnancy; the critical role of placental
      tryptophan metabolism and transport.

PMID- 11512019
TI  - Neuronal nicotinic acetylcholine receptors and autosomal dominant nocturnal
      frontal lobe epilepsy: a critical review.
AB  - Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is a distinct human
      epileptic syndrome. In some families, it is associated with mutations of the
      alpha4 or the beta2 subunit of the neuronal nicotinic acetylcholine receptor
      (nAChR). It has been suggested that these mutations are the causative factors
      responsible for the induction and expression of this syndrome. However, the
      pathogenic mechanisms leading to ADNFLE are unknown and, in this review, we
      discuss the following yet unresolved questions concerning the involvement of
      mutated nAChRs in the phenotypic development of the disorder: (1) why do seizures
      associated with ADNFLE arise explicitly from the frontal lobe of the neocortex?
      (2) why do the seizures arise mainly from sleep? (3) why does ADNFLE starts
      predominantly during childhood? A survey of our current knowledge on neocortical
      and thalamic cholinergic systems, including their ontogenetic development, leads
      us to the conclusion that there are, at least at the moment, no convincing
      answers to these questions. Furthermore, we believe that, even in those cases
      where mutations of the alpha4 or the beta2 subunit of the nAChR cosegregate with
      ADNFLE, there must be some crucial additional factors contributing to the
      development of the specific symptoms of ADNFLE.

PMID- 11512020
TI  - Intranephron localization and regulation of the V1a vasopressin receptor during
      chronic metabolic acidosis and dehydration in rats.
AB  - The intrarenal localization and role of the V1a vasopressin receptor in body
      fluid homeostasis are unclear. We investigated the intranephron localization of
      V1a receptor mRNA and protein using reverse transcription (RT)-competitive
      polymerase chain reaction (PCR) and immunohistochemistry with a specific
      polyclonal antibody. To determine whether the V1a receptor is involved in the
      regulation of acid-base balance, we also examined the effects of acute and
      chronic metabolic acidosis and dehydration on V1a receptor expression. V1a mRNA
      was expressed most abundantly in the cortical collecting ducts (CCD) and
      decreased in the deeper CD. Expression in the glomeruli and thick ascending limbs
      was low. The immunohistochemical study revealed the presence of the V1a receptor
      in the glomeruli, the thick ascending limbs and the CD. Dehydration decreased V1a
      mRNA expression in the CD. Chronic metabolic acidosis increased V1a receptor mRNA
      expression in the CD but decreased V2 receptor mRNA expression. Western blot
      analysis revealed up-regulation of the V1a receptor protein in chronic metabolic
      acidosis. Incubation of microdissected CCD or outer medullary CD (OMCD) in a low
      pH (or or low-HCO3-) medium increased the levels of V1a receptor mRNA but
      decreased V2 receptor mRNA expression. Incubating OMCD with arginine vasopressin
      (AVP) and the V1a receptor antagonist (OPC21268) increased V2 receptor mRNA
      expression compared with incubation with AVP alone. These data suggest that V1a
      receptors are present primarily in the principal and intercalated cells in the CD
      and that these receptors are involved in the regulation of water and acid-base
      balance.

PMID- 11512021
TI  - Effects of triiodothyronine and bovine growth hormone on glucose transporter
      isoform-2 (GLUT-2) and glucokinase (GK) gene expression in pancreatic islets of
      fetal and adult rats.
AB  - This study was conducted to determine the effects of triiodothyronine (T3) and
      bovine growth hormone (bGH) on the expression of glucose transporter-2 (GLUT-2)
      and of glucokinase (GK) from pancreatic islets of fetal and adult rats.
      Incubation of both sets of pancreatic islets with T3 did not modify GLUT-2 mRNA
      levels, but did reduce the content of GLUT-2 protein, while it reduced the
      expression of GK mRNAs in fetal and adult pancreatic islets. Treatment of fetal
      and adult pancreatic islets with 1 microg/ml bGH did not alter the expression of
      GLUT-2 mRNAs, but significantly increased GLUT-2 protein levels in adult islets
      by 50%. Also, bGH had no effect on the GK mRNA content of fetal and adult
      pancreatic islets whereas, in contrast, there was a significant reduction in the
      amount of GK protein in fetal islets cultured with that hormone but not in those
      corresponding to adult rats. These findings suggest that T3 and bGH are able to
      modulate the expression of GLUT-2 and GK mRNAs and proteins in pancreatic islets
      in a manner different from that in the liver, as previously reported by others.
      In addition, both hormones produced different responses in fetal and in adult
      pancreatic islets.

PMID- 11512022
TI  - Characterisation of a human acid-sensing ion channel (hASIC1a) endogenously
      expressed in HEK293 cells.
AB  - Acid-sensing ion channels (ASICs) are a new and expanding family of proton-gated
      cation (Na+/Ca2+) channels that are widely expressed in sensory neurons and the
      central nervous system. Their distribution suggests that they may play a critical
      role in the sensation of the pain that accompanies tissue acidosis and may also
      be important in detecting the subtle pH variations that occur during neuronal
      signalling. Here, using whole-cell patch-clamp electrophysiology and reverse
      transcriptase-polymerase chain reaction (RT-PCR), we show that HEK293 cells, a
      commonly used cell line for the expression and characterisation of many ion
      channels, functionally express an endogenous proton-gated conductance
      attributable to the activity of human ASIC1a. These data therefore represent the
      first functional characterisation of hASIC1 and have many important implications
      for the use of HEK293 cells as a host cell system for the study of ASICs,
      vanilloid receptor-1 and any other proton-gated channel. With this latter point
      in mind we have devised a simple desensitisation strategy to selectively remove
      the contribution of hASIC1a from proton-gated currents recorded from HEK293 cells
      expressing vanilloid receptor-1.

PMID- 11512023
TI  - Role of actin filaments in endothelial cell-cell adhesion and membrane stability
      under fluid shear stress.
AB  - Clostridium botulinum C2 toxin (C2 toxin) and purified ADP-ribosylated-alpha
      actin (ADP-r-alpha-actin) cause specific actin depolymerisation in living cells.
      This effect was used to investigate the actin microfilament system with
      particular emphasis on cell-cell adhesion and plasma membrane integrity in
      endothelial cells. C2 toxin caused time- and dose-dependent (15-100 ng/ml)
      changes in endothelial surface morphology (investigated by atomic force
      microscopy), intercellular gap formation and cell detachment under shear stress.
      Low concentrations of C2 toxin (1.5 ng/ml), however, did not induce cell
      detachment but inhibited shear stress-dependent cell alignment. Gap formation as
      well as cell loss under shear stress was also observed in cells microinjected
      with purified ADP-r-alpha-actin. Intercellular gap formation was mediated by
      increased alpha-catenin solubility (40%) due to actin filament depolymerisation.
      Disintegration of plasma membranes (measured by LDH release) and cell
      fragmentation during simultaneous exposure to shear stress and C2 toxin were due
      to a loss of more than 50% of membrane-associated actin. These data show that
      small disturbances in actin dynamics inhibit shear stress-dependent cell
      alignment; that depolymerisation of actin filaments increases the solubility of
      alpha-catenin, thus resulting in cell dissociation and that actin filaments of
      the membrane cytoskeleton are required to protect the cells from haemodynamic
      injury such as shear stress. Together, the study shows a heterogeneous regulation
      of actin filament dynamics at subcellular locations. Junction-associated actin
      filaments displayed the highest sensitivity whereas stress fibres were far more
      stable.

PMID- 11512024
TI  - 18-beta-Glycyrrhetinic acid (BGA) as an electrical uncoupler for intracellular
      recordings in confluent monolayer cultures.
AB  - In the study of epithelial cell biology, primary cell cultures or cell lines
      grown to confluency offer considerable advantages compared with isolated cells
      and cell clusters. This is due mainly to the development of appropriate cell-to
      cell contacts that are a prerequisite for cell polarity and thus vectorial solute
      transport. On the other hand, electrical coupling via gap junctions in most
      instances significantly hinders the use of voltage-clamp techniques for
      electrophysiological analysis of transport processes in single cells. In the
      present study we employed the gap junctional blocker 18-beta-glycyrrhetinic acid
      (BGA) to reduce electrical cell-to-cell coupling in confluent primary cultures of
      rat hepatocytes. In current-clamp experiments, 40 micromol/l BGA reversibly
      increased apparent cell input resistance approximately tenfold. Due to this
      partial electrical isolation of cells, two-channel voltage-clamp experiments
      became feasible and, for the first time, the hypertonicity-induced Na+
      conductance of rat hepatocytes could be analysed quantitatively. In ion
      substitution experiments, however, it became obvious that BGA, while leaving Na+
      and K+ conductances virtually unchanged, completely blocked cell membrane Cl-
      conductance. This additional effect of BGA necessitates independent control
      experiments to ensure that the transport process under consideration is itself
      not changed by the compound. Nevertheless, BGA may serve as a powerful tool for
      the quantitative electrophysiological study of epithelial cells that are in quasi
      physiological contact with their neighbours.

PMID- 11512025
TI  - Differential roles of the sodium-calcium exchanger in renin secretion and renal
      vascular resistance.
AB  - The intracellular free calcium concentration ([Ca2+]i) is a central regulator of
      renin secretion and the contractility of vascular smooth muscle cells. As [Ca2+]i
      results from calcium influx and calcium extrusion, we were interested in the role
      of the Na+/Ca2+-exchanger as an important calcium-extrusion pathway in the
      regulation of renin secretion. Therefore, we investigated the effects of
      inhibiting the Na+/Ca2+-exchanger, either by reducing the extracellular sodium
      concentration ([Na+]e) or using pharmacological tools, on renin secretion and
      vascular resistance in the isolated perfused rat kidney model. Stepwise
      reductions of [Na+]e led to progressive (up to sevenfold) increases in renal
      vascular resistance ([Na+]e 7 mM) whilst renin secretion rates were not altered
      significantly. Similarly, pharmacological blockade of the Na+/Ca2+-exchanger by
      benzamil (100 microM) or KB-R7943 (30 microM) resulted in significant
      vasoconstrictions without altering basal renin secretion rates. Also renin
      secretion that was pre-stimulated by isoproterenol (10 nM), blockade of macula
      densa salt transport by bumetanide (100 microM) or lowering the perfusion
      pressure to 40 mmHg was not attenuated by Na+/Ca2+-exchanger inhibition, although
      the vascular resistance increased significantly. In contrast, angiotensin II (100
      pM) reduced pre-stimulated renin secretion values by 50%. The subsequent lowering
      of the [Na+]e however did not augment the inhibition of renin secretion, although
      the renal vascular resistance increased markedly. We conclude that the Na+/Ca2+
      exchanger has no functional role in the regulation of [Ca2+]i in juxtaglomerular
      cells controlling renin secretion, whereas it markedly affects the preglomerular
      vascular smooth muscle cells of the renal vasculature.

PMID- 11512026
TI  - The disulfonic stilbene DIDS and the marine poison maitotoxin activate the same
      two types of endogenous cation conductance in the cell membrane of Xenopus laevis
      oocytes.
AB  - In the present experiments we exposed the intra- or extracellular surface of
      excised giant membrane patches of Xenopus laevis oocytes bathed in 140 mmol/l Na
      aspartate solution to the anion transport inhibitor 4,4'-diisothiocyanatostilbene
      2,2'-disulfonate (DIDS, 250 micromol/l). We observed that DIDS activated at least
      two cation conductances: (1) a non-selective cation (NSC) conductance that was
      mediated by channels of approximately 27 pS and resembled the stretch-activated
      cation conductance that has been observed in the oocyte cell membrane previously,
      and (2) a Na+-selective conductance, the single-channel events of which could not
      be resolved and which resembled the depolarization-induced Na+ conductance that
      has also been observed in the oocyte cell membrane previously. Both conductances
      were blocked by 1 mmol/l amiloride from the intra- and extracellular surfaces but
      inhibition of the NSC conductance by extracellular amiloride was less pronounced.
      Both conductances activated only slowly with a delay of 15-60 s after application
      of DIDS and remained active even after DIDS was washed off. This suggests that
      DIDS caused the exocytosis of preformed channels and this interpretation was
      supported by our additional observation that extracellular application of
      maitotoxin (MTX) mimicked the effects of DIDS. MTX is a marine toxin that has
      recently been reported to induce exocytosis in Xenopus laevis oocytes. The fact
      that DIDS and MTX each carry two sulfonyl groups suggests that they act on the
      same positively charged binding sites of an exocytosis-inducing protein. Our
      observations demonstrate that using DIDS to inhibit heterologously expressed
      anion transporters in the cell membrane of Xenopus laevis oocytes may compromise
      proper determination of the transporter currents. This effect can be prevented if
      the DIDS-activated endogenous cation conductances are suppressed by application
      of amiloride to the cytoplasmic surface of the cell membrane.

PMID- 11512027
TI  - The renal Na-HCO3-cotransporter expressed in Xenopus laevis oocytes: inhibition
      by tenidap and benzamil and effect of temperature on transport rate and
      stoichiometry.
AB  - In the present experiments we expressed the rat kidney Na+-HCO3- cotransporter
      (rkNBC) in Xenopus laevis oocytes to reinvestigate the flux coupling ratio under
      improved measuring conditions. Essentially the current/voltage (I/V) relationship
      of isolated inside-out giant membrane patches was measured and the stoichiometric
      ratio was calculated from the reversal potential (VI=0) of the cotransport
      current (INBC). INBC was defined as that part of the total current that was
      suppressed when rkNBC was inhibited. Previously we have used the disulfonic
      stilbene DIDS to inhibit rkNBC, but we now found that tenidap or benzamil are
      better suited as inhibitors. Tenidap blocked rkNBC rapidly and reversibly both
      from the intra- and extracellular surface with half maximal inhibition at 13
      micromol/l and it did not cause the same potentially disturbing side effects as
      DIDS. In addition, we found that the endogenous depolarization-induced Na+
      conductance of the oocyte, which may compromise the I/V analysis, can be
      suppressed by applying 1 mmol/l amiloride to the cytosolic surface of the patch.
      The new measuring conditions greatly increased the yield of successful
      experiments. The distribution of 27 measurements of VI=0 obtained at near
      physiological Na+ and HCO3- concentrations and in absence of Cl-, K+ and
      cytosolic Ca2+ showed that the calculated stoichiometric ratios closely
      approached the value of 2 HCO3-:1 Na+ if the expression density of rkNBC was
      high. This result fully confirms our previous observations. Further experiments
      showed that the difference between the stoichiometric ratio of 3:1 observed in
      rat proximal tubule in vivo and the present value is not due to the temperature
      difference. We conclude that, depending on local modulatory influences, rkNBC can
      operate with different stoichiometric ratios and the present data and those
      reported in an accompanying publication [Muller-Berger et al., Pflugers Arch
      (2001) DOI 10.1007/s004240100592] show that these ratios are integer numbers i.e.
      either 2:1 or 3:1.

PMID- 11512028
TI  - The renal Na-HCO3-cotransporter expressed in Xenopus laevis oocytes: change in
      stoichiometry in response to elevation of cytosolic Ca2+ concentration.
AB  - The Na+-HCO3- cotransporter of rat kidney (rkNBC) was expressed in Xenopus laevis
      oocytes to test whether cytosolic Ca2+ ([Ca2+]i) affects the cotransport
      stoichiometry. The current/voltage relationship of giant inside-out membrane
      patches of rkNBC-expressing oocytes was measured at near-physiological Na+ and
      HCO3- concentrations and the cotransport current, INBC, was defined as the
      current inhibited by 0.25 mmol/l tenidap. Essentially, we determined the reversal
      potential (VI=0) of INBC and the slope conductance (gNBC). The coupling ratio of
      (HCO3-) to Na+ (q) was calculated from VI=0. As reported in the preceding
      publication [Ducoudret et al., Pflugers Arch (2001) DOI 10.1007/s004240100594],
      in Ca2+-free solutions q was 2:1. This did not change when [Ca2+]i was increased
      to 0.1 micromol/l. At 0.5 micromol/l, however, only a few patches showed q=2:1,
      while most patches exhibited q=3:1. This indicates that [Ca2+]i affected the
      transport function of membrane-resident rkNBC molecules, and the bimodal
      distribution of VI=0 points to an indirect effect possibly mediated by
      differently expressed Ca2+-dependent protein kinases. The shift in q was
      associated with the predicted near twofold increase in gNBC and was confirmed by
      measurements of VI=0 at different Na+ and HCO3- concentrations. Because we
      previously observed that the cotransport in proximal tubule cells is susceptible
      to carbonic anhydrase (CA) inhibition, but only if it works at q=3:1, we propose
      that kNBC has three transport sites: when working at q=2:1 it binds 2 (HCO3-)+1
      Na+, and while at q=3:1 it binds 1 CO3(2-)+1 HCO3- +1 Na+. The latter is
      equivalent to the transfer of 3 (HCO3-) +1 Na+, because in the presence of CA the
      generation of 1 CO3(2-) on one side of the membrane and its disintegration on the
      other transiently liberates 1 CO2, which follows by diffusion. This model
      explains the increase in (HCO3-) transport that is associated with the change in
      q from 2:1 to 3:1 by a selectivity change of a binding site from HCO3- to CO3(2
      ). This is more likely than the induction of a new transport pouch for a third
      (HCO3-) ion, which would require exceedingly large conformational changes of the
      transport protein.

PMID- 11512029
TI  - Oral contraceptives alter sleep and raise body temperature in young women.
AB  - Female reproductive steroids, oestrogen and progesterone, not only affect
      reproductive function, but also thermoregulation and sleep. Chronic
      administration of synthetic steroids, as occurs in women taking oral
      contraceptives, may affect these regulatory systems differently from endogenous
      oestrogen and progesterone. We therefore investigated body temperature and sleep
      in ten young women taking oral contraceptives, in the active and placebo phases
      of the contraceptive pack, and compared them to a group of nine women with
      ovulatory cycles, in the mid-follicular and mid-luteal phases. Body temperature
      was raised throughout 24 h in the women taking oral contraceptives in the active
      phase, and in the naturally cycling women in the luteal phase, compared to the
      follicular phase. The women taking oral contraceptives in the placebo phase,
      however, continued to have raised body temperatures, similar to those in the
      active phase, indicating a prolonged action of synthetic reproductive steroids on
      body temperature. Sleep also was influenced by the endogenous and synthetic
      reproductive steroids, but independently of body temperature. The women taking
      oral contraceptives had more stage-2 non-rapid eye movement sleep in the active
      phase, both compared to their placebo phase and the naturally cycling women. The
      naturally cycling women, however, had more slow wave sleep in the luteal phase
      compared to the contraceptive group of women. Exogenous reproductive steroids
      therefore influence body temperature and sleep differently from endogenous
      progesterone and oestrogen.

PMID- 11512030
TI  - Hypoxia/fatigue-induced degradation of troponin I and troponin C: new insights
      into physiologic muscle fatigue.
AB  - Conditions such as respiratory failure and cardiopulmonary arrest can expose the
      diaphragm to hypoxemia. In skeletal muscles, fatiguing stimulation renders
      muscles hypoxic, which has long been known to dramatically reduce muscle
      function. We have previously demonstrated that fatiguing stimulation under
      hypoxic conditions disrupts both the excitation-contraction coupling (ECC)
      process and the isometric contractile properties (ICP) in intact diaphragm muscle
      strips and the contractile properties of skinned fibers isolated from these
      muscles. Here we have analyzed the effects of intermittent fatiguing stimulation
      on specific muscle proteins in muscle strips from mouse diaphragms that have been
      exposed to hypoxia. We report for the first time that the effects of hypoxia
      fatigue, namely to decrease maximal tetanic force, maximal calcium-activated
      force and calcium sensitivity of the mouse diaphragm muscle, are associated with
      the degradation of troponins TnI and TnC (Western blot analysis). The
      concentrations of TnT and actin did not change under these same conditions.
      Because troponins are integrally involved in regulating the interaction between
      actin and myosin during the cross-bridge cycle, the degradation of TnI and TnC
      may explain the effects of hypoxia-fatigue on the ICP. This interpretation is
      supported by the observations that extraction of troponins from control skinned
      fibers mimics the effects of hypoxia-fatigue on contractile function and that
      incorporation of native troponins into fibers isolated from hypoxic-fatigued
      muscles partially restores function.

PMID- 11512031
TI  - Changes of skeletal muscle proteases activities during a chronic low-frequency
      stimulation period.
AB  - Modifications of muscular contractile patterns by chronic low-frequency
      stimulation induce structural, physiological, and biochemical transformations in
      fast-twitch fibers that cause them to act like slow-twitch muscle. During this
      transformation many changes in protein pattern appear and the proteolytic system
      may be involved in those changes. The activities of cathepsin L, B, H, D, the
      level of cystatin, as well as the calpain activity in rabbit fast-twitch muscle
      have been compared with those of slow-twitch muscle. The results show that fast
      twitch muscle has lower cathepsin activities and higher calpain activities than
      slow-twitch muscle. Chronic low-frequency stimulation was applied for 24 days to
      fast-twitch muscles and changes in proteases and protease inhibitors (cystatin
      and calpastatin) were studied. After 7-14 days of stimulation, lysosomal
      cathepsin L, B, and D and cytoplasm calpain and proteosome activities increased
      several-fold. Involvement of the phagocyte cells in the protein fiber turnover
      was minimal. Although the turnover of contractile proteins during muscle
      electrostimulation takes place in synchrony with changes in the muscle
      proteolytic system, the stimulation period used did not attain the total
      transformation from fast- to slow-twitch muscle proteolytic pattern.

PMID- 11512032
TI  - Sulfonylurea receptors inhibit the epithelial sodium channel (ENaC) by reducing
      surface expression.
AB  - In the kidney the epithelial Na+ channel (ENaC) is co-expressed with the
      sulfonylurea receptor (SUR), an ABC protein that shares a high degree of homology
      with the cystic fibrosis transmembrane conductance regulator (CFTR) and
      reportedly modifies ENaC in various preparations. To investigate a possible
      regulatory relationship between SUR and ENaC, we performed co-expression studies
      on Xenopus laevis oocytes, which were assayed for amiloride-sensitive currents
      (DeltaIami). Moreover, a chemiluminescence assay was used to investigate the
      surface expression of extracellular hemagglutinin-tagged SUR1 (SUR1-HA) or HA
      tagged ENaC (ENaC-HA). In oocytes co-injected with SUR1/ENaC (or SUR2B/ENaC)
      DeltaIami was reduced by congruent with 53% (or congruent with 45%) compared to
      DeltaIami measured in matched control oocytes injected with ENaC alone. The
      inhibitory effect of SUR on DeltaIami was preserved in oocytes expressing ENaC
      with C-terminally truncated subunits. Co-expression of SURs did not confer
      sensitivity of DeltaIami to diazoxide, pinacidil, tolbutamide, or glibenclamide.
      ENaC does not facilitate the surface expression of SUR1-HA, which is known to be
      retained in the endoplasmatic reticulum (ER) by an ER-retention/retrieval signal.
      SUR1-HAAAA, a mutant that lacks this signal, still inhibits ENaC currents.
      Chemiluminescence was reduced by congruent with 49% in oocytes co-expressing ENaC
      HA/SUR1 compared to that in control oocytes expressing ENaC-HA alone. We conclude
      that SUR does not interact with ENaC at the level of the plasma membrane but that
      it inhibits DeltaIami by reducing surface expression of the channel.

PMID- 11512033
TI  - Changes in the mechanical and adhesive behaviour of human neutrophils on cooling
      in vitro.
AB  - Changes in the rheological properties of neutrophils may influence flow in
      microvessels that are cooled below normal body temperature. We investigated the
      effects of temperature on the mechanical and adhesive properties of human
      neutrophils by measuring transit times for individual cells flowing through 8
      microm-pores in filters, and adhesion to P-selectin for cells perfused over a
      monolayer of activated platelets. Pore transit time increased as temperature was
      decreased from 37 degrees C to 0 degrees C. Upon rapid cooling, there was an
      instantaneous increase attributable to changes in aqueous viscosity.
      Interestingly, at 10 degrees C specifically, there was an additional increase in
      transit time, which was abolished by the inhibitor of actin polymerization,
      cytochalasin B. This meant that by 15 min, transit time at 10 degrees C was
      greater than at 0 degrees C. Most adherent cells on P-selectin were rolling,
      rather than stationary, at 10, 26 or 37 degrees C. The velocity of rolling slowed
      with decreasing temperature. The total number of adherent cells decreased with
      increasing wall shear rate, but for a given shear rate there was relatively
      little effect of temperature on attachment. However, when adhesion at 10, 26 or
      37 degrees C was compared at equal shear stress (taking into account fluid
      viscosity), adhesion was greatest at 10 degrees C. Measurements of
      immunofluorescence showed that exposure to 10 degrees C gradually increased
      expression of beta2-integrin CD11b/CD18, but this did not cause transformation to
      stationary adhesion with time in the flow assay. Thus, neutrophils show an
      anomalous rheological response around 10 degrees C, which may impair local
      microcirculation in the cold. On rewarming, "activated" cells might inhibit
      recovery or become released into the systemic circulation.

PMID- 11512034
TI  - The role of a swelling-activated taurine transport pathway in the regulation of
      articular chondrocyte volume.
AB  - Swelling articular chondrocytes by reducing osmolarity stimulates a taurine
      transport pathway, which is implicated in regulatory volume decrease (RVD) in
      various cell types. The present study investigated factors controlling the
      activity of this pathway in chondrocytes, in particular (1) the effects of the
      acute (seconds) and chronic (hours) exposure of chondrocytes to anisotonic media,
      and (2) whether there is a role for metabolites from the arachidonic acid cascade
      in activating the taurine transport pathway. For in situ and isolated
      chondrocytes, the point at which swelling-activated [14C]taurine efflux was
      stimulated (the "set-point") corresponded closely to the osmolarity of the
      incubation medium (180, 280 or 380 mosmol/l). However, the volume of chondrocytes
      isolated into these media and measured by confocal microscopy was not different (
      congruent with 645 microm3). Activity of the swelling-activated taurine transport
      pathway was inhibited by REV5901 (an inhibitor of steps of the arachidonic acid
      cascade; K0.5 8+/-4 microM), NDGA (a general lipoxygenase inhibitor; K0.5 28+/-5
      microM), or MK886 (an inhibitor of the 5-lipoxygenase-activating protein; 91%
      inhibition at 10 microM), but weakly by the more potent 5-lipoxygenase inhibitor
      REV5901 para (K0.5 350+/-100 microM). Addition of the leukotriene (LT) B4 or D4
      receptor antagonists, CP-105,696 and L660,711 respectively, or of the
      leukotrienes LTB4, LTC4, LTD4 and LTE4 or lipoxins (hepoxylin A3 or B3) had no
      effect on the activity of the pathway in isotonic or hypotonic media. The role of
      the pathway in RVD was determined in isolated calcein-loaded chondrocytes using
      fluorescence imaging. RVD was observed and inhibited by REV5901 (50 microM) and
      by NDGA (75 microM). The data show that despite chronic exposure of chondrocytes
      to anisotonic media, the cells maintain a pre-determined volume that is the "set
      point" for the activation of the taurine transport pathway following acute
      hypotonic challenge. This pathway appears to play a role in chondrocyte RVD, but
      its activation does not involve metabolites of the arachidonic acid cascade.

PMID- 11512035
TI  - Molecular determinants for apical expression of the renal type IIa Na+/Pi
      cotransporter.
AB  - Type IIa and IIb Na+/Pi-cotransporters have different patterns of expression in
      vivo: IIa is expressed in apical membranes of renal proximal tubules, and IIb in
      intestinal and lung epithelia. They are found in different subcellular locations
      when transfected in epithelial cells: IIa is apically expressed in renal proximal
      cells (OK), but mostly intracellularly in intestinal cells (CaCo2); IIb is apical
      in both cell types. To identify the domains responsible for the different
      expression of both cotransporters (in CaCo2), as well as those responsible for
      the apical expression of IIa (in OK), mutated cotransporters were fused to the
      Enhanced Green Fluorescent Protein (EGFP), and their expression analyzed by
      confocal microscopy. We conclude that the apical expression information for CaCo2
      is contained within the C-terminal tail of IIb, but is not contained within IIa.
      From analysis of mutated IIa cotransporters we identified residues, within the C
      terminal tail, involved in the apical expression of these cotransporters in OK
      cells: internal PR-residues and terminal TRL-residues. These signals are
      functional in OK but not in CaCo2-cells, supporting the concept that polarized
      targeting can be protein and cell specific.

PMID- 11512036
TI  - Evidence for two mechanisms of amino acid osmolyte release from hippocampal
      slices.
AB  - A 30% decrease in osmolarity stimulated 3H-taurine, 3H-GABA and glutamate
      (followed as 3H-D-aspartate) efflux from rat hippocampal slices. 3H-taurine
      efflux was activated rapidly but inactivated slowly. It was decreased markedly by
      100 microM 5-nitro-(3-phenylpropylamino)benzoic acid (NPPB) and 600 microM
      niflumic acid and inhibited strongly by tyrphostins AG18, AG879 and AG112 (25-100
      microM), suggesting a tyrosine kinase-mediated mechanism. Hyposmolarity activated
      the mitogen-activated protein kinases (MAPK) extracellular-signal-related kinase
      1/2 (ERK1/ERK2) and p38, but blockade of this reaction did not affect 3H-taurine
      efflux. Hyposmosis also activated phosphatidylinositide 3-kinase (PI3K) and its
      prevention by wortmannin (100 nM) essentially abolished 3H-taurine efflux. 3H
      taurine efflux was insensitive to the protein kinase C (PKC) blocker
      chelerythrine (2.5 microM) or to cytochalasin E (3 microM). The release of 3H
      GABA and 3H-D-aspartate occurred by a different mechanism, characterized by rapid
      activation and inactivation, insensitivity to NPPB, niflumic acid, tyrphostins or
      wortmannin. 3H-GABA and 3H-D-aspartate efflux was not due to external [NaCl]
      decrease, cytosolic Ca2+ increase or depolarization, or to reverse operation of
      the carrier. This novel mechanism of amino acid release may be mediated by Ca2+
      independent exocytosis and modulated by PKC and actin cytoskeleton disruption, as
      suggested by its inhibition by chelerythrine and potentiation by 100 nM phorbol
      12-myristate-13 acetate (PMA) and cytochalasin E. GABA and glutamate
      osmosensitive efflux may explain the hyposmolarity-elicited increase in amplitude
      of inhibitory and excitatory postsynaptic potentials in hippocampal slices as
      well as the hyperexcitability associated with hyponatraemia.

PMID- 11512037
TI  - The NMDA antagonist memantine attenuates the expression of opioid physical
      dependence in humans.
AB  - RATIONALE: Preclinical observations suggest that NMDA receptor-mediated
      glutamatergic neurotransmission is involved in the expression and maintenance of
      opioid dependence. OBJECTIVE: The present study evaluated whether memantine, the
      clinically available non-competitive NMDA receptor antagonist, decreases naloxone
      precipitated withdrawal in morphine-dependent humans. METHODS: Eight heroin
      dependent, non-treatment seeking, inpatient participants were stabilized on a
      fixed dose of morphine (30 mg PO qid). Subsequently, they received a series of
      challenges with naloxone (0.4 mg, IM) and the severity of opioid withdrawal was
      monitored. Either placebo or memantine (60 mg PO) was given 6 h before each
      naloxone challenge. A modified multiple baseline, across-participants design was
      used to evaluate the effects of memantine on the severity of naloxone
      precipitated opioid withdrawal. RESULTS: Naloxone increased ratings and produced
      physical changes consistent with opioid withdrawal. Memantine attenuated the
      severity of opioid withdrawal as assessed with the Clinical Institute for
      Narcotic Withdrawal Scale scale. Withdrawal was significantly reduced when
      naloxone was administered at 6 and 52 h after memantine, but not when
      administered 126 h (5 days) after memantine. Medication effects, assessed 5 h
      after memantine administration and before naloxone administration, included
      significant increases in ratings of "strong" and "good" drug effect, and "I feel
      sedated", "mellow", and "high". CONCLUSIONS: Memantine attenuated the expression
      of opioid physical dependence in humans, indicating that glutamatergic
      neurotransmission at the NMDA receptor site contributes to the maintenance of
      opioid dependence. This finding suggests that memantine may be a useful adjunct
      in the treatment of opioid dependence.

PMID- 11512038
TI  - Oral dyskinesias and morphological changes in rat striatum during long-term
      haloperidol administration.
AB  - RATIONALE: Neuroleptic-induced oral dyskinesias in rats, a putative analogue to
      human tardive dyskinesia, may be due to increased glutamate release within the
      striatum. This may lead to excitotoxic degeneration and, as a consequence,
      persistent motor side effects. OBJECTIVES: To investigate whether alterations in
      glutamatergic synapses within the striatum are associated with the development of
      neuroleptic-induced oral dyskinesia. METHODS: Haloperidol was administered for 20
      weeks, and rats with high and low levels of vacuous chewing movements (VCM) were
      analyzed for morphological changes with electron microscopy at three time points.
      RESULTS: At week 8, the high VCM rats had a larger nerve terminal area and lower
      density of nerve terminal glutamate immunoreactivity than the other groups. After
      18 weeks of treatment, the nerve terminal area was increased relative to controls
      in both the high and low VCM groups. After discontinuation of treatment, there
      were no significant morphological differences between the groups, but the level
      of VCM was still significantly increased in the high VCM group. CONCLUSIONS:
      These results show that striatal glutamatergic transmission is affected during
      haloperidol treatment and the nerve terminal area and the density of nerve
      terminal glutamate immunoreactivity are important in determining the VCM response
      to haloperidol treatment. This indicates that increased glutamatergic synaptic
      activity in the striatum contributes to the development of human tardive
      dyskinesia.

PMID- 11512039
TI  - Reliability and validity of alcohol-induced heart rate increase as a measure of
      sensitivity to the stimulant properties of alcohol.
AB  - RATIONALE: Alcohol-induced heart rate (HR) stimulation during the rising limb of
      the blood alcohol curve reliably discriminates between individuals at
      differential risk for alcoholism, and appears to be a potential
      psychophysiological index of psychomotor stimulation from alcohol. OBJECTIVES:
      Three studies are presented which explore the reliability and convergent and
      discriminant validity of this alcohol response index. METHODS: Young men with and
      without a multigenerational family history of alcoholism were administered a 1.0
      ml/kg dose of 95% USP alcohol. Resting baseline cardiac and subjective measures
      were assessed before and after alcohol consumption. RESULTS: Study 1 demonstrated
      that alcohol-induced HR stimulation was significantly and positively related to
      alcohol-induced changes in mood. Study 2 demonstrated that alcohol-induced HR
      stimulation was reliable across two alcohol administration sessions (r=0.33-0.66,
      P<0.01). Study 3 explored the relationship between the proposed index and
      measures of sensitivity to alcohol previously linked to genetic predisposition to
      alcoholism. Multiple regression analysis indicated that alcohol-induced HR
      increase and reduced subjective intoxication (measured using the Subjective High
      Assessment Scale) were both positively associated with alcohol-induced changes in
      mood states that have previously been shown to be sensitive to the effects of
      stimulant drugs and the reinforcing effects of alcohol. CONCLUSIONS: Sensitivity
      to alcohol-induced heart-rate stimulation during the ascending limb of the blood
      alcohol curve may be a useful and informative marker for understanding
      susceptibility to alcoholism.

PMID- 11512040
TI  - Predictable individual differences in the initiation of cocaine self
      administration by rats under extended-access conditions are dose-dependent.
AB  - RATIONALE: The characterization of self-administration (SA) under extended access
      conditions is necessary for the development of addiction models. OBJECTIVE: The
      purposes of this experiment were to investigate: (1) dose effects on the
      initiation of cocaine SA under extended access conditions; (2) predictable
      individual differences in SA under these conditions and their relationships to
      neuroendocrine function and cocaine dose. METHODS: After they were tested for
      their locomotor responses to novelty and to cocaine and trained to lever-press
      under a food-reinforced schedule, male Sprague-Dawley rats were allowed to SA
      cocaine (0.25, 0.5, 1.0, or 2.0 mg/kg per infusion, IV) by lever-pressing under a
      FR1 schedule during five consecutive daily 10-h sessions. Plasma corticosterone
      (CORT) and prolactin (PRL) were measured throughout the experiment. RESULTS: Rats
      tested at higher cocaine doses more readily acquired and showed increased drug
      intake and more regular patterns of SA. High responders (HR) to novelty self
      administered greater amounts of cocaine, acquired more rapidly and displayed more
      regular SA compared to LR rats, but only at the lowest cocaine dose tested (i.e.,
      0.25 mg/kg per infusion). HR rats also exhibited a greater high-dose escalation
      of SA compared to LR rats. Novelty-induced (but not cocaine-induced) locomotor
      activity, pre-SA plasma CORT, and pre-SA food-reinforced lever-pressing predicted
      SA, but only at the lowest cocaine dose tested. No differences in plasma CORT or
      PRL were observed between LR and HR rats. CONCLUSIONS: The present findings
      indicate that predictable individual differences in cocaine SA under extended
      access conditions are relevant only at low doses and are surmountable by
      increasing the available dose of cocaine.

PMID- 11512041
TI  - Analgesia induced by chronic nicotine infusion in rats: differences by gender and
      pain test.
AB  - RATIONALE: Acute administration of nicotine induces analgesia with subsequent
      development of tolerance. In human studies, females are less sensitive to the
      analgesic effects of nicotine than males. Few previous animal studies have
      investigated analgesic effects of chronic nicotine administration or addressed
      gender differences. OBJECTIVES: To investigate whether chronic administration of
      nicotine induces analgesia in male and female rats as assessed by a battery of
      standard pain assays, if tolerance develops, and if hyperalgesia occurs following
      cessation of nicotine. METHODS: Nicotine (free base; 6 mg/kg/day i.v.) or saline
      was administered for 2 weeks via implanted osmotic pumps. Pain behavior was
      assessed before, during, and for 3 weeks after nicotine infusion by measuring
      tail flick latency, hot-plate latency, and thermal paw withdrawal latency. The
      paw-withdrawal threshold to non-noxious mechanical stimuli was also measured.
      Effects of nicotine infusion, gender, and time were assessed by three-way
      analyses of variance. RESULTS: Both male and female rats exhibited a comparable
      degree of analgesia in the hot-plate test with development of tolerance during
      the 2-week infusion period. Males, but not females, showed analgesia in the tail
      flick test. Analgesia was not observed for thermally evoked paw withdrawal in
      either males or females, nor did nicotine affect non-noxious mechanically evoked
      paw withdrawals. Males and females showed cessation of weight gain during the
      first week of nicotine infusion. CONCLUSIONS: Chronic nicotine-induced analgesia
      was confirmed in both male and female rats as assessed using the hot-plate test
      which reflects integrated pain behavior. Males, but not females, exhibited
      analgesia in a nociceptive withdrawal reflex test (tail flick), indicating that
      nicotine-induced analgesia may depend on both the type of pain test and gender.
      The lack of nicotine-induced analgesia assessed by the tail flick reflex test in
      female rats is consistent with recent human studies showing that nicotine reduces
      pain elicited by brief noxious cutaneous stimulation in male but not female
      subjects.

PMID- 11512042
TI  - Glucose facilitation of cognitive performance in healthy young adults:
      examination of the influence of fast-duration, time of day and pre-consumption
      plasma glucose levels.
AB  - RATIONALE: Previous investigations have demonstrated increased performance after
      the administration of a glucose-load on certain aspects of cognitive functioning
      in healthy young adults. Generally these studies have used a procedure where
      participants were tested in the morning after an overnight fast. OBJECTIVE: The
      aim of the present study was, for the first time, to investigate the glucose
      cognitive facilitation effect under more natural testing times and with shorter
      duration of the previous fast. METHODS: Measures of verbal and non-verbal memory
      performance were compared under different fasting intervals (2-h fast versus
      overnight fast), times (morning versus afternoon) and glycaemic conditions
      (glucose versus aspartame drinks) in healthy young participants. RESULTS: There
      was a significant glucose facilitation effect on long-term verbal memory
      performance. In addition, glucose significantly enhanced long-term spatial memory
      performance. The effect of glucose was essentially equivalent whether it was
      given after an overnight fast or a 2-h fast following breakfast or lunch. There
      was no effect of drink and time of day on working memory performance.
      CONCLUSIONS: The results of this study further support the hypothesis that
      glucose administration can enhance certain aspects of memory performance in
      healthy young adults. More significantly, the findings indicate that this
      cognitive facilitation effect persists under more naturalistic conditions of
      glucose administration and is not restricted to long fast durations or morning
      administration.

PMID- 11512043
TI  - Neuroendocrine serotonergic and dopaminergic responsivity in male schizophrenic
      patients during treatment with neuroleptics and after switch to risperidone.
AB  - RATIONALE: The pharmacological profile of risperidone is that of an atypical
      neuroleptic regarding its serotonin 5-HT2A and dopamine D2 receptor blocking
      properties. Treatment with risperidone, though, results in considerably elevated
      plasma prolactin (PRL) levels which are not observed with other atypical
      neuroleptics, such as clozapine, indicating a differentiated action on receptors
      that are involved in PRL release, mainly dopaminergic and serotonergic.
      OBJECTIVE: To assess the responsivity of serotonergic and dopaminergic receptors
      during treatment with neuroleptics and after switch to risperidone, using
      neuroendocrine paradigms. METHODS: Two neuroendocrine challenge tests, measuring
      the PRL increases induced by acute administration of serotonergic (clomipramine,
      25 mg i.v.) and dopaminergic (haloperidol, 5 mg i.m.) drugs were performed in 13
      male schizophrenic patients during treatment with typical neuroleptics and,
      later, after 6 weeks of treatment with risperidone. The tests were also performed
      in a group of nine healthy male volunteers. PRL was estimated in blood samples
      taken every 15 min for 1 h for clomipramine and every 30 min for 2 h for
      haloperidol. Psychopathology was assessed using the Brief Psychiatric Rating
      Scale (BPRS). RESULTS: During treatment with neuroleptics (mean dose 1354 mg
      chlorpromazine equivalents, range 300-2400 mg), i.m. haloperidol caused
      significant elevations in plasma PRL, which were totally abolished after 6 weeks
      treatment with risperidone (mean dose 12.1 mg/day, range 8-16 mg/day), indicating
      complete D2 receptor blockade. In contrast, the PRL increases obtained after
      clomipramine administration during neuroleptic treatment were preserved after
      treatment with risperidone. Both PRL response patterns to clomipramine were
      similar to that of healthy controls. BPRS score was 50.2+/-9.3 points during
      neuroleptic treatment and was reduced after risperidone to 30.1+/-6.6 points,
      i.e., 40% in the mean. CONCLUSIONS: During treatment with typical neuroleptics,
      the PRL responses to clomipramine are normal, and they are preserved after switch
      to risperidone in doses that cause complete dopamine receptor blockade.
      Risperidone, a dopamine and 5-HT receptor blocker, does not affect 5-HT receptors
      that are involved in the PRL release by the 5-HT uptake blocker clomipramine,
      indicating a different behavior than other atypical neuroleptics such as
      clozapine or olanzapine, for which a reduction of the PRL release induced by
      serotonergic agents like fenfluramine or mCPP has been reported. A conclusive
      identification of the 5-HT receptor subtypes that are involved in this different
      action cannot be identified at present, but it should be taken into account that
      risperidone differs from clozapine, showing higher affinity for 5-HT2A than 5
      HT2C receptors and lacking the marked affinity of clozapine to 5-HT1A receptors.

PMID- 11512044
TI  - In vivo 5-HT2A receptor blockade by quetiapine: an R91150 single photon emission
      tomography study.
AB  - BACKGROUND: Atypical antipsychotic drugs are thought to show a high degree of 5
      HT2A receptor blockade, which may prevent the emergence of extrapyramidal
      symptoms. METHOD: 5-HT2A binding was estimated using 123I-5-I-R91150 and single
      photon emission tomography (SPET) in six schizophrenic subjects treated with
      quetiapine at a mean (+/-SD) daily dose of 350+/-123 mg for at least 5 weeks and
      a matched sample of six healthy volunteers. Clinical and side-effect ratings were
      performed at baseline and at the time of SPET scanning. The reference region
      approach was used to define a 5-HT2A binding index in the frontal and temporal
      cortex. RESULTS: Quetiapine treatment resulted in a significant decline in 5-HT2A
      receptor availability in the frontal cortex (mean 0.98+/-0.09) relative to
      healthy volunteers (mean 1.33+/-0.16). All patients showed improvements in
      clinical symptom or side-effect ratings. The mean frontal cortex:cerebellum ratio
      after quetiapine treatment was significantly negatively correlated with reduction
      in the Abnormal Involuntary Rating scale and Simpson-Angus scores (P<0.05
      Bonferroni corrected), but not with the reduction in the scores from the scale
      for the assessment of positive symptoms, the scale for the assessment of negative
      symptoms, the Montgomery-Asberg depression rating scale or patient age.
      CONCLUSION: Quetiapine treatment results in significant in vivo blockade of
      cortical 5-HT2A, similar to other atypical antipsychotic drugs. This effect may
      contribute to its placebo level extrapyramidal side-effect profile.

PMID- 11512045
TI  - Attentional bias associated with alcohol cues: differences between heavy and
      occasional social drinkers.
AB  - RATIONALE: Previous research has shown an attentional bias toward drug-related
      stimuli in opiate addicts and toward emotionally threatening words in anxiety
      patients. OBJECTIVE: The primary aim of this study was to investigate whether non
      dependent heavy social drinkers would differ in their selective attention towards
      alcohol-related stimuli in comparison with a group of occasional social drinkers.
      METHODS: Attentional bias was assessed using alcohol-related pictures and words
      in a dot probe detection task. Picture and word pairs were visually presented,
      followed by a dot probe that replaced one of the items. Attentional bias was
      determined from latencies in responding to the dot probe. Questionnaires were
      used to examine the relationships among attention, outcome expectancies after
      alcohol consumption, and personality traits. Higher-order executive function was
      also measured with two cognitive tasks, recognition memory and attentional shift.
      RESULTS: The heavy social drinkers showed an attentional bias towards the alcohol
      related stimuli when compared to the occasional social drinkers. The heavy social
      drinkers also scored more highly on expectancy factors of sociability and
      sexuality and lower on the personality traits of self-directedness and
      persistence. CONCLUSION: The results support cognitive theories of addictive
      behaviour in which the ability of drug-related stimuli to capture attention is
      suggested to play a part in drug dependence, craving and relapse.

PMID- 11512046
TI  - Methamphetamine self-administration by humans.
AB  - RATIONALE: Methamphetamine abuse has become increasingly problematic. Yet, the
      reinforcing effects of methamphetamine in humans have not been systematically
      evaluated. OBJECTIVE: To characterize methamphetamine's reinforcing effects in
      human research participants under controlled laboratory conditions. METHODS:
      Eight healthy research volunteers (one female, seven males) completed this 20-day
      residential study. On days 1, 5, 9, 13 and 17, at 1000 hours, participants
      received the "sample" oral dose of methamphetamine (0, 5, 10 mg) that was
      available for the next 3 days and they also received an alternative reinforcer, a
      $1 voucher (redeemable for cash at study's end). Over a 3-day period, volunteers
      participated in an eight-trial choice procedure, during which they had the
      opportunity to self-administer the dose of methamphetamine they most recently
      sampled or to receive the $1 voucher. RESULTS: Participants' choice to self
      administer methamphetamine significantly increased when active methamphetamine (5
      mg and 10 mg) was available compared to placebo. No difference of choice was
      noted between low-dose and high-dose methamphetamine. However, the sampled 10 mg
      methamphetamine dose significantly increased several "positive" subjective
      ratings including "High," "Good Drug Effect," and "Stimulated," whereas the
      sampled 5 mg methamphetamine dose did not. Both active methamphetamine doses
      caused significant reductions in daily total caloric intake, relative to the
      respective placebo conditions. CONCLUSION: These data demonstrate that oral
      methamphetamine is a positive reinforcer in humans.

PMID- 11512047
TI  - Studies on the neuroprotective effect of the enantiomers of AR-A008055, a
      compound structurally related to clomethiazole, on MDMA ("ecstasy")-induced
      neurodegeneration in rat brain.
AB  - RATIONALE: 3,4-Methylenedioxymethamphetamine (MDMA, "ecstasy") administration
      produces neurotoxic degeneration of 5-HT nerve endings in several regions of rat
      brain. Administration of the GABAmimetic drug clomethiazole protects against this
      damage. OBJECTIVE: We wished to see whether the enantiomers of AR-A008055 (1-4
      methyl-5-thiazolyl-1-phenyl-methylamine), a compound structurally related to
      clomethiazole, were also neuroprotective against MDMA-induced degeneration.
      METHODS: (R)-(+)-AR-A008055 or (S)-(-)-AR-A008055 (100 mg/kg IP) was injected 5
      min prior to and 55 min after MDMA (15 mg/kg IP) administration to Dark Agouti
      rats. Rectal temperature was measured during this time and the concentration of 5
      HT and 5-HIAA measured in hippocampus, cortex and striatum 7 days later. [3H]
      Paroxetine binding was also measured in cortex. RESULTS: Both enantiomers
      abolished the acute MDMA-induced hyperthermia and attenuated the subsequent
      neurotoxic loss of 5-HT, 5-HIAA and [3H]-paroxetine binding. When rats given the
      enantiomer plus MDMA were warmed to keep their rectal temperature elevated to
      near that of animals given only MDMA, the neuroprotective effect of (S)-(-)-AR
      A008055 was still seen, while the effect of (R)-(+)-AR-A008055 was abolished.
      Protection was also seen when (S)-(-)-AR-A008055 (50 mg/kg) was given, a dose
      which produced only a modest attenuation of MDMA-induced hyperthermia.
      CONCLUSIONS: The current data suggest that a major proportion of the
      neuroprotective action of (S)-(-)-AR-A008055 did not involve an attenuating
      effect on MDMA-induced hyperthermia. The protection afforded by (R)-(+)-AR
      A008055, which is not a GABA agonist, appears to be solely due to its action on
      body temperature, strengthening the contention that abolishing the acute MDMA
      induced hypothermia can produce neuroprotection. Since (S)-(-)-AR-A008055 has a
      similar pharmacology to clomethiazole, these data suggest that drugs which
      increase GABAA receptor channel opening are neuroprotective against MDMA-induced
      damage.

PMID- 11512048
TI  - Effects of high-affinity GABAB receptor antagonists on active and passive
      avoidance responding in rodents with gamma-hydroxybutyrolactone-induced absence
      syndrome.
AB  - RATIONALE: Absence seizures in man are behaviourally manifested as arrest and
      mild jerks mainly of facial muscles, associated in the electroencephalogram with
      synchronous spike and wave discharges. Gamma-hydroxybutyrolactone (GHBL)
      administration is currently used as an experimental model of absence seizures in
      rats and mice. OBJECTIVE: The aim of the present study was to examine the effects
      of three potent gamma-aminobutyric acid (GABA)B receptor antagonists CGP55845A,
      CGP62349 and CGP71982 (0.01 mg/kg) on the development of GHBL-induced absence
      epilepsy and in learning paradigms of active and passive avoidance tests in GHBL
      treated mice and rats. METHODS: After 4 weeks of development of the absence
      syndrome, active and passive avoidance tests with negative reinforcement were
      performed. In both animal species, the absence syndrome was observed after 3
      weeks of treatment in the saline group. RESULTS: The GABAB receptor antagonists
      CGP55845A and CGP62349 appeared to suppress the development of the absence
      syndrome to a greater degree in mice than in rats. CGP71982 suppressed it later
      than the other two antagonists (fifth week). In an active avoidance test in GHBL
      treated mice, the GABAB antagonists had different effects - CGP62349 improved
      learning and memory retention to a greater extent than CGP55845A, whilst CGP71982
      had no influence on it. In a passive avoidance test in GHBL-treated mice, the
      GABAB antagonists also had different effects - CGP71982 improved both learning
      and memory retrieval, whereas CGP55845A and CGP62349 had no effect. In the active
      avoidance test in GHBL-treated rats, the GABAB antagonist CGP55845A improved
      learning, whereas the other two, CGP62349 and CGP71982, had no effect. In the
      passive avoidance test the GHBL-treated rats showed an improvement in short
      memory retrieval. CGP55845A and CGP71982 improved this further, whilst CGP62349
      had no effect. CONCLUSIONS: GHBL appeared to influence mice and rats in a
      different manner - rats learned the active avoidance task better than the GHBL
      treated mice. The present study confirms previous data that GABAB antagonists
      suppress absence behaviour.

PMID- 11512049
TI  - Stereotypic behaviors in mice selectively bred for high and low methamphetamine
      induced stereotypic chewing.
AB  - RATIONALE: At high doses, methamphetamine produces repetitive stereotypic
      behaviors, and the degree to which this occurs is heritable. OBJECTIVES: Mice of
      a B6D2F2 genetic background were selectively bred for four generations for high
      (HMA) and low (LMA) numbers of stereotyped chewing episodes measured for 1 min at
      33 min post-injection following 10 mg/kg methamphetamine (changed to 7 mg/kg for
      the high line and 15 mg/kg for the low line in the third selected generation to
      avoid ceiling and floor effects, respectively). We sought to determine whether
      stereotypic behaviors other than number of repetitive chewing episodes were
      altered by the selective breeding process. METHODS: HMA and LMA mice of the third
      and fourth selected generations were tested for chewing stereotypy, for a number
      of other stereotypic behaviors previously observed in rodents, and for several
      other non-stereotypic responses to methamphetamine. Testing in the third selected
      generation was conducted by observing behaviors on videotape following 7 mg/kg
      methamphetamine. In the fourth selected generation, mice were also tested in
      automated activity monitors following 10 mg/kg methamphetamine and in climbing
      chimneys following 16 mg/kg methamphetamine. Dose-response curves with doses of
      1, 2, 3.5, 7, 10, and 15 mg/kg methamphetamine were constructed for the most
      commonly observed behaviors. RESULTS: LMA mice, which exhibited low stereotyped
      chewing, exhibited high stereotyped circling and climbing, and the reverse was
      true for these behaviors for HMA mice. For most of the other behaviors measured,
      there were drug effects but no differences between selected lines. CONCLUSIONS:
      These results suggest that these three stereotyped behaviors, chewing, circling,
      and climbing, at least partly share the same mechanisms, and therefore are
      influenced by at least some of the same genes, since animals selectively bred for
      low methamphetamine-induced stereotyped chewing exhibited high amounts of
      circling and climbing when given methamphetamine. This also suggests that the
      other stereotypic behaviors that we measured do not occur by the same genetically
      determined mechanisms as stereotypic chewing.

PMID- 11512050
TI  - Effects of nicotine and mecamylamine-induced withdrawal on extracellular dopamine
      and acetylcholine in the rat nucleus accumbens.
AB  - RATIONALE: Prior research suggests that high levels of acetylcholine (ACh) in the
      nucleus accumbens (NAc) are associated with aversive states such as morphine
      withdrawal, but this has not been tested for nicotine withdrawal. OBJECTIVES: The
      goal was to test the hypothesis that acute nicotine decreases extracellular ACh
      and increases extracellular dopamine (DA) in the NAc, while withdrawal from
      nicotine causes an opposite neurochemical imbalance with high extracellular ACh
      and low DA. METHODS: Rats were prepared with a microdialysis probe in the NAc
      (primarily the shell region). They received one injection of nicotine (0.5 mg/kg,
      s.c.) or chronic nicotine (9 mg/kg per day via osmotic minipump). RESULTS: Naive
      animals receiving acute nicotine showed a mild, significant increase in both ACh
      (122% of baseline) and DA (124%). After chronic nicotine administration for 7
      days, the nicotinic antagonist mecamylamine (1.0 mg/kg, s.c.) precipitated
      withdrawal with the appearance of somatic signs (teeth chattering and
      shakes/tremors) and a significant increase in extracellular ACh to 125% of
      baseline, while extracellular DA decreased to 65%. Control groups receiving
      saline in place of nicotine or mecamylamine did not show these effects.
      CONCLUSIONS: Earlier work suggests that the observed release of accumbens ACh and
      DA in response to acute nicotine administration may be a factor in nicotine
      induced suppression of appetite. ACh release during withdrawal, coupled with the
      decrease in extracellular DA may play a role in the aversive aspects of nicotine
      withdrawal that contribute to dependency.

PMID- 11512052
TI  - Intragraft expression of p38 and activated p38 MAPK (mitogen-activated protein
      kinase) in rat small bowel transplantation.
AB  - Recent studies suggest that cytotoxic T-lymphocytes expressing p38 mitogen
      activated protein kinase (p38MAP kinase) contribute to allograft rejection in
      clinical heart transplantation. Interleukin-2 (IL-2), a potent T cell mitogen,
      activates the p38MAP kinase pathway, resulting in phosphorylation of target
      transcription factors. In this study we investigated the expression of activated
      p38MAP kinase in intragraft cell infiltrates following rat heterotopic small
      bowel transplantation and examined the effects of the immunosuppressant FK506 on
      intragraft expression of activated p38MAP kinase and allograft rejection.
      Allografts receiving FK506 (0.5 mg/kg per day i. m.) for 7 days as primary anti
      rejection therapy had a significant reduction in histopathological evidence of
      allograft rejection on Day 7, compared to allograft controls. In addition,
      Western blotting analysis of intragraft cell infiltrates showed a reduction in
      the expression of activated p38MAP kinase in allografts treated with FK506. We
      conclude that intragraft cell infiltrate expression of activated p38MAP kinase is
      an important marker of acute rejection in this animal model of small bowel
      transplantation, and that FK506 is an effective immunosuppressant, in this
      situation, that may act in part by preventing the activation of p38MAP kinase.

PMID- 11512051
TI  - The in vitro pharmacology of the beta-adrenergic receptor pet ligand (s)
      fluorocarazolol reveals high affinity for cloned beta-adrenergic receptors and
      moderate affinity for the human 5-HT1A receptor.
AB  - RATIONALE: s-Fluorocarazolol [(S)-FCZ] is the major positron emission tomography
      (PET) ligand currently used to visualize central beta-adrenergic receptors in
      vivo, although its pharmacology is incompletely known. OBJECTIVE: Our objective
      was to comprehensively characterize the in vitro pharmacology of (S)- and (R)-FCZ
      to determine its suitability for study of central and peripheral beta-adrenergic
      receptors. METHODS: We characterized the in vitro pharmacology of (S)-FCZ at 42
      biogenic amine receptors and transporters in vitro using the resources of the
      National Institute of Mental Health Psychoactive Drug Screening Program. RESULTS:
      As expected (R)- and (S)-FCZ had high affinities for beta-adrenergic receptors
      (Ki values=0.08-0.45 nM) and negligible affinities (Ki values>100 nM) for nearly
      all other tested receptors and transporters with the exception of the h5-HT1A
      receptor for which (S)-FCZ had high affinity (Ki=34 nM). Interestingly, (R)-FCZ
      had low affinity for the h5-HT1A receptor (Ki=342 nM). CONCLUSION: The high
      affinity of (S)-FCZ for the h5-HT1A receptor is not likely to interfere with
      studies of peripheral beta-adrenergic receptors, since 5-HT1A receptors are
      expressed at very low levels outside the central nervous system. Indeed, computer
      simulations predict that even at low ligand concentrations, 5-HT1A binding in
      brain regions like hippocampus are likely to be substantial. Thus, (S)-FCZ may
      not be a suitable PET ligand for studies of central nervous system beta
      adrenergic receptors unless the contribution by 5-HT1A sites can be shown to be
      negligible.

PMID- 11512053
TI  - Reversible hepatofugal portal flow after liver transplantation using a small-for
      size graft from a living donor.
AB  - We describe a case of reversible hepatofugal portal flow 1 week after
      transplantation of a small-for-size liver graft from a living donor. A transient
      increase in intrahepatic portal vascular resistance was the suspected cause. The
      portal venous flow normalized after residual collateral channels had been
      interrupted surgically. The patient was discharged on the 90th postoperative day.
      Liver transplant clinicians should be aware that hepatofugal flow can occur with
      small-for-size liver grafts, despite sufficient portal venous flow immediately
      after transplantation.

PMID- 11512054
TI  - Interventional radiologic procedures in liver transplantation.
AB  - Postoperative biliary and vascular complications contribute significantly to
      morbidity and mortality in liver transplantation. Interventional radiologists are
      an integral part of the multidisciplinary team necessary for optimizing the
      management of these complications. During a 15-year period, 39 cadaveric and 25
      living related liver transplantations were performed at the Chang Gung Memorial
      hospital, Taiwan. Of 64 liver transplant recipients, 9 (3 adult and 6 pediatric)
      underwent 13 interventional radiological procedures for the treatment of biliary
      sludge-casts (n = 2), bile duct occlusion or stenosis (n = 2), hepatic veins
      thrombosis (n = 1), hepatic veins stenosis (n = 1), portal vein stenosis with
      splenorenal shunting (n = 1), biloma (n = 1), and infected fluid collection or
      ascites (n = 4). Antegrade or retrograde interventional approach was used to
      successfully treat all biliary complications, and all percutaneous drainage
      procedures were effective in the control of intra-abdominal fluid collections.
      Portal vein stenosis was treated by balloon dilatation, and the associated
      splenorenal shunt was closed by metallic coil embolization via transhepatic
      catheterization of the portal vein. Hepatic vein stenosis was effectively treated
      by balloon dilatation and expandable metallic stent deployment via transfemoral
      and jugular venous approaches, respectively. Hepatic vein thrombosis was only
      partially lysed by transvenous streptokinase administration, and surgical
      thrombectomy was needed to achieve complete recanalization. The total success
      rate of the interventional procedures was 92 % with no procedure-related
      complications. The overall survival rate in this series is 89 %, and all patients
      who underwent living related liver transplantation maintain to date a 100 %
      survival rate. We can conclude that interventional radiological procedures are
      very useful for managing biliary and vascular complications after liver
      transplantation. These techniques provide a cure in most situations, thus
      obviating the need for further surgical intervention or re-transplantation.

PMID- 11512055
TI  - Increased tacrolimus levels during diarrhea.
AB  - While it is well known that diarrhea results in decreased trough levels of
      cyclosporin A, experience with levels of tacrolimus (FK506) and diarrhea is
      limited. We have therefore measured the tacrolimus trough levels of four male and
      two female recipients of solid organs before, during, and after gastroenteritis.
      The average age of these six patients was 31 (1-60) years. Four patients had
      received a kidney transplant, one patient had undergone simultaneous kidney
      pancreas transplantation, and another patient had received a liver transplant.
      Rotavirus was identified in the feces specimen of a 1-year-old child that had
      undergone liver transplantation. All patients showed an elevated tacrolimus
      trough level (peak 20-60 ng/ml) after onset of gastroenteritis. Under symptomatic
      therapy and adequate adjustment of tacrolimus dose, the gastroenteritis stopped
      and tacrolimus levels returned to the therapeutic range. We recommend that FK506
      levels be carefully monitored during diarrhea in order to prevent intoxication.

PMID- 11512056
TI  - Rabbit antithymocyte globulin versus OKT3 induction therapy after heart-lung and
      lung transplantation: effect on survival, rejection, infection, and obliterative
      bronchiolitis.
AB  - The superiority of different induction therapies after heart-lung and lung
      transplantation is not clearly established; specifically, whether monoclonal
      (OKT3) or polyclonal antibody induction therapy provides any advantage. Between
      1989 and 1991 we used induction therapy with either rabbit antithymocyte globulin
      (RATG) or OKT3, given at random based on the availability of RATG. RATG was used
      in 25 patients (RATG group 1) and OKT3 in 38 patients (OKT3 group 1). Early
      results suggested a survival advantage with RATG. From 1992 until 1997 we used
      RATG induction therapy in 108 patients (RATG group 2). This study analyzed longer
      term survival, infection, rejection, and obliterative bronchiolitis (OB) rates
      for RATG group 1 and OKT3 group 1 and assessed outcomes for RATG group 2. The 1-,
      3-, and 5-year survival for RATG group 1 was 72 %, 72 %, and 52 % and for OKT3
      group 1 was 63 %, 49 %, and 34 % (P < 0.05). The 1- and 3-year survival for RATG
      group 2 was 84 % and 74 %. The 1-, 3-, and 5-year actuarial freedom rates from
      lung rejection for RATG group 1 were 38 %, 38 %, and 31 % and for OKT3 group 1
      were 21 %, 0 %, and 0 % (P < 0.01). The linearized rate (events/100 patient days)
      of all infections at 3 months was 1.55 +/- 0.28 for RATG group 1 and 2.19 +/-
      0.27 for OKT3 group 1 (P = NS). The infection rate for RATG group 2 was 1.60 +/-
      0.13. The actuarial rates of freedom from OB at 1, 3, and 5 years for RATG group
      1 were 84 %, 51 %, and 45 % and for OKT3 group 1 were 77 %, 61 %, and 36 % (P =
      NS), while for RATG group 2 the rates were 97 % and 92 % at 1 and 3 years (P <
      0.01 vs RATG group 1 and OKT3 group 1). The use of RATG induction therapy from
      1989 through 1991 resulted in improved actuarial survival and less rejection,
      without increased infection rates. The use of RATG since 1992 has continued to
      result in similar outcomes for survival, infection, and rejection. The time to
      onset of OB has improved further in recent years. This may be a result of recent
      improvements in cytomegalovirus (CMV) prophylaxis.

PMID- 11512057
TI  - Rapid exchange of large numbers of donor- and host leukocytes after human liver
      transplantation.
AB  - After liver transplantation, the release of donor leukocytes into the host and
      the uptake of host leukocytes by the graft is one of the earliest immunologic
      interactions between donor and host. Using three-color flow cytometry, these
      interactions were investigated in eight patients from 5 min-24 h after receiving
      HLA unmatched liver grafts. Five minutes after reperfusion, 5.0 % +/- 1.4 % of
      all blood leukocytes in the host were of donor origin, decreasing to 1.1 % +/-
      0.8 % after 24 h. Donor granulocytes preferentially disappeared from the host
      circulation, whereas no differences were found between NK-cells and various B-
      and T cell subpopulations. Furthermore, host granulocytes were preferentially
      retained in the donor liver. Thus, despite extensive pre-operative perfusion,
      more than 10(9) donor leukocytes quickly leave the liver graft while host
      granulocytes preferentially accumulate there. A better understanding of the
      molecular mechanisms mediating these early interactions might help to develop new
      strategies for diagnosis and therapy of liver graft rejection.

PMID- 11512058
TI  - Impact of current cryopreservation procedures on mechanical and functional
      properties of human aortic homografts.
AB  - We evaluated the impact f standard cryopreservation on mechanical and functional
      properties of human aortic homografts. From 14 human heart-valve donors, the
      thoracic descending aorta was obtained. Effects of cryopreservation on mechanical
      (elastic properties and breaking stress) and smooth muscle cell (SMC) and
      endothelium function were tested. Cryopreservation (cryo) did not significantly
      affect Young's modulus of elastin (fresh: 3.1 +/- 1.0, cryo: 2.7 +/- 0.9 x 10(5)
      Nm(-2)), collagen recruitment pressure (fresh: 1.1 +/- 0.3, cryo: 1.1 +/- 0.4 x
      10(4) Nm(-2)), distensibility (fresh: 3.8 +/- 1.8, cryo: 3.6 +/- 1.6 x 10(5) N(
      1)m2), or breaking stress (fresh: 2.4 +/- 1.0, cryo: 2.2 +/- 1.0 x 10(6) Nm(-2)).
      Following explantation, no endothelium-dependent relaxation was found. SMC
      function and endothelium-independent relaxation were mainly intact after
      explantation but significantly decreased after cryopreservation. Aortic
      mechanical properties are not influenced by cryopreservation. Following
      explantation, almost no endothelial cell function is present, and SMC
      contractility is strongly affected after cryopreservation.

PMID- 11512059
TI  - Deletrious effect of prolonged cold ischemia on renal function.
AB  - The detrimental effect of prolonged cold ischemia (CI) on posttransplant renal
      function has long been recognized. However, the cellular consequences of CI have
      not been clearly defined. This study describes a model for the identification of
      CI-induced injury by evaluating ex-vivo renal metabolism and function prior to
      reperfusion. Small bovine kidneys were cold stored in Viaspan for 24-, 48-, 72-,
      and 96 h. Kidneys were then warm perfused (32 degrees C) using Exsangiunous
      Metabolic Support (EMS) technology and evaluated for oxidative metabolism,
      vascular dynamics and function. Oxygen consumption, vascular resistance, and
      diuresis were stable in kidneys with CI up to 48 h. After 72- and 96 h of CI,
      vascular resistance was increased while oxygen consumption and diuresis were
      reduced (P < 0.05). Glomerular filtration rate was diminished at CI greater than
      24 h (P < 0.05). Results show that function was compromised with CI greater than
      24 h and preceded the loss of cell viability following 48 h of CI.

PMID- 11512060
TI  - A short course of high-dose cyclophosphamide induces long-term survival of
      intestinal allografts in mice.
AB  - Several transplant programs have recently added cyclophosphamide (CyP) to their
      immune suppression protocols in an attempt to reduce intestinal graft rejection
      rates. The present study was undertaken to confirm the benefits of this drug in a
      murine small bowel transplant model. A short course of monotherapy with CyP 20
      mg/kg per dose resulted in a mean survival time (MST) of 17.5 +/- 3.6 days,
      compared with a MST of 7.5 +/- 0.7 days in the untreated controls (P < 0.01).
      Cyclosporin A (CsA) 30 mg/kg per day produced comparable survival rates when used
      as monotherapy (MST: 14.2 +/- 1.3 days) or in combination with CyP 20 mg/kg per
      dose (MST: 21.3 +/- 5.1 days). Treatment with high dose CyP (40 mg/kg per dose)
      completely prevented graft loss in 8 of 10 animals (MST: 72.5 +/- 5.3 days, P <
      0.01). However, adding CsA abrogated the induction of long-term survival achieved
      by CyP alone (MST: 23 +/- 0.4 days). These data have important implications for
      the use of CyP in clinical transplantation.

PMID- 11512061
TI  - Bronchiolitis obliterans organizing pneumonia (BOOP) with suspected liver graft
      versus-host disease after allogeneic bone marrow transplantation.
AB  - We report on a patient with chronic myelogenous leukemia who developed
      bronchiolitis obliterans organizing pneumonia (BOOP) after allogeneic bone marrow
      transplantation (BMT). A 19-year-old Japanese male complained of dry cough and
      dyspnea 7 months after BMT. The chest X-ray and computed tomography revealed
      patchy infiltrates bilaterally. Lung function test, lung biopsy and
      bronchoalveolar lavage were consistent with the diagnosis of BOOP. The patient
      also suffered from suspected graft-versus-host disease (GVHD) of the liver, after
      discontinuation of cyclosporine. Furthermore, prednisolone proved effective
      against the BOOP and the liver dysfunction. These findings indicate that BOOP is
      a possible pulmonary manifestation of chronic GVHD, and that immunological
      mechanisms may have effected the onset of BOOP after BMT in this case.

PMID- 11512062
TI  - Hepatic vein obstruction due to hypertrophy of right split-liver adult allograft.
AB  - The increasing shortage of liver allografts has led to the development of split
      liver transplantation. More frequent applications have permitted the resolution
      of most of its technical complications. A hitherto unreported complication of
      split liver transplantation, hepatic vein obstruction caused by hypertrophy of a
      right split-liver adult allograft, is discussed. As surgical correction was
      impossible, the outflow obstruction was treated successfully with interventional
      radiology.

PMID- 11512063
TI  - Microsporidiosis in the graft of a renal transplant recipient.
AB  - Microsporidia are intracellular protozoa that are emerging as significant
      opportunistic infections in AIDS patients. Although there are numerous published
      reports of intestinal and disseminated infections in patients with AIDS, there
      have been only two previous reports in transplantation medicine, both on
      intestinal microsporidiosis. We report here the first documented case of extra
      intestinal microsporidiosis in a transplant recipient. A 39-year-old renal
      transplant recipient presented with a pyrexia and deteriorating graft function.
      Light microscopic examination of a renal allograft biopsy revealed numerous
      microsporidian spores within the renal tubular epithelium. Transmission electron
      microscopy confirmed the presence of an Encephalitozoon infection and was highly
      suggestive of Encephalitozoon intestinalis. Therapy with albendazole was
      extremely effective and resulted in recovery of renal function. Although a rare
      cause of renal allograft dysfunction, microsporidiosis is curable. It may be
      underdiagnosed, and should be considered in the differential diagnosis of
      transplant recipients presenting with opportunistic infections.

PMID- 11512064
TI  - Abstracts of the 13th International Congress of DentoMaxilloFacial Radiology.
      Glasgow, United Kingdom, 5-8 August 2001.

PMID- 11512070
TI  - Functional electrical stimulation for grasping and walking: indications and
      limitations.
AB  - This review describes the state of art in the field of Functional Electrical
      Stimulation (FES) and its impact on improving grasping and walking functions in
      acute and chronic Spinal Cord Injured (SCI) patients. It is argued that during
      the early rehabilitation period the FES systems with surface stimulation
      electrodes should be used to assist training of hand and leg movements in SCI
      patients. Our clinical trials have shown that a number of acute SCI patients with
      impaired walking and grasping functions could improve these functions due to
      training with an adjustable FES system to the point that they finally did not
      need the FES system to carry out these tasks. Other acute SCI patients, who did
      not recover the desired function, were enabled to perform either walking or
      grasping with the FES assistance. We believe that the subjects who can perform
      grasping or walking with the help of FES, and still use the neuroprosthesis 6
      months after being subjected to the FES training, should consider the FES system
      as a prosthetic device in Activities of Daily Living (ADL). Despite the
      significant technical progress achieved in the last 10 to 15 years in the FES
      field, there is a general consensus that these systems are not sufficiently
      advanced and that they need further development. The limited acceptance of the
      FES technology can be in part explained by the fact that it is not completely
      mature and that the patients still require daily assistance to use the FES
      systems. Nevertheless the present FES treatments combined with conventional
      occupational and physical therapy still remain the most promising approach in
      rehabilitating SCI patients. In this review, advantages and limitations of
      different FES systems that are used to restore grasping and walking functions are
      discussed.

PMID- 11512072
TI  - The acute effects of continuous and conditional neuromodulation on the bladder in
      spinal cord injury.
AB  - STUDY DESIGN: Laboratory investigation using serial slow-fill cystometrograms.
      OBJECTIVES: To examine the acute effects of different modes of dorsal penile
      nerve stimulation on detrusor hyperreflexia, bladder capacity and bladder
      compliance in spinal cord injury (SCI). SETTING: Spinal Injuries Unit, Royal
      National Orthopaedic Hospital, Stanmore, Middlesex, UK. METHODS: Fourteen SCI
      patients were examined. Microtip transducer catheters enabled continuous
      measurement of anal sphincter, urethral sphincter and intravesical pressures.
      Control cystometrograms were followed by stimulation of the dorsal penile nerve
      at 15 Hz, 200 micros pulse width and amplitude equal to twice that which produced
      a pudendo-anal reflex. Stimulation was either continuous or in bursts of one
      minute triggered by a rise in detrusor pressure of 10 cm water (conditional).
      Further control cystometrograms were then performed to examine the residual
      effects of stimulation. RESULTS: Bladder capacity increased significantly during
      three initial control fills. Continuous stimulation (n=6) significantly increased
      bladder capacity by a mean of 110% (+/-Standard Deviation 85%) or 173 ml (+/-146
      ml), and bladder compliance by a mean of 53% (+/-31%). Conditional stimulation in
      a different group of patients (n=6) significantly increased bladder capacity, by
      144% (+/-127%) or 230 ml (+/-143 ml). In the conditional neuromodulation
      experiments, the gap between suppressed contractions fell reliably as bladder
      volume increased, and the time from start of stimulation to peak of intravesical
      pressure and 50% decline in intravesical pressure rise was 2.8 s (+/-0.9 s) and
      7.6 s (+/-1.0s) respectively. The two methods of stimulation were compared in six
      patients; in four out of six conditional neuromodulation resulted in a higher
      mean bladder capacity than continuous, but the difference was not significant.
      CONCLUSIONS: Both conditional and continuous stimulation significantly increase
      bladder capacity. The conditional mode is probably at least as effective as the
      continuous, suggesting that it could be used in an implanted device for bladder
      suppression.

PMID- 11512071
TI  - Intrathecal baclofen in tetraplegia of spinal origin: efficacy for upper
      extremity hypertonia.
AB  - STUDY DESIGN: Retrospective analysis. OBJECTIVES: To evaluate the efficacy of
      intrathecal baclofen (ITB) for upper extremity spastic hypertonia in tetraplegia
      of spinal origin. SETTING: University of Alabama at Birmingham hospital. METHODS:
      The medical records of 14 individuals with tetraplegia of spinal origin who
      underwent intrathecal baclofen pump placement were reviewed. The effects of
      intrathecal baclofen on spasm frequency, deep tendon reflexes, and tone (Ashworth
      scale) were assessed for the upper and lower extremities for a 1-year follow-up
      period. RESULTS: There were statistically significant declines in upper extremity
      spasm scores (1.8 points, P=0.012), reflex scores (1.4 points, P<0.0001) and
      Ashworth scores (0.6 points, P<0.0001) for the 1-year follow-up period. For the
      lower extremities, all decreases were significant (P<0.0001). There was also a
      statistically significant (P<0.0001) increase in intrathecal baclofen dosage
      requirements during the 1-year follow-up period to maintain the reductions in
      spasm frequency, reflexes and tone. CONCLUSIONS: Intrathecal baclofen is a safe
      and effective intervention for treating upper extremity hypertonia of spinal
      origin. In addition, the level of intrathecal catheter placement is felt to be of
      importance.

PMID- 11512073
TI  - Single stage decompression, anterior interbody fusion and posterior
      instrumentation for tuberculous kyphosis of the dorso-lumbar spine.
AB  - STUDY DESIGN: To evaluate the role of single stage decompression with anterior
      interbody fusion with posterior instrumentation and deformity correction of
      tuberculous kyphosis of the dorso-lumbar spine in patients with/without
      neurological deficit. OBJECTIVES: (1) To evaluate the amount of kyphosis
      correction with single stage surgery and its progression with time. (2) To
      evaluate the neurological recovery. (3) To evaluate the bony anterior interbody
      fusion. SETTING: King Edward Memorial Hospital, Bombay, India. METHODS: Twenty
      eight patients with post-tuberculous kyphosis deformity averaging 64.3 degrees
      (range 17 to 105) were treated by a single stage posterolateral decompression,
      correction of kyphosis, anterior interbody fusion and posterior instrumentation.
      RESULTS: The mean kyphosis correction obtained was 62.5% with the mean post
      operative kyphosis angle reducing to 24.1 (range 5-60). At a mean follow-up of
      5.8 years (4-7 years) the mean kyphosis angle loss was 3.2 degrees (range 0-5
      degrees ). Of the 23 patients with neurological deficit, recovery was seen in 21
      cases (91.3%) while deterioration was seen in one case (4.3%). The remaining five
      patients were neurologically intact pre-operatively. Bony fusion was seen in all
      cases at 9 months. One patient with subpulmonary function died post-operatively
      (mortality 3.5%). CONCLUSION: The results of our series are encouraging. However
      single stage decompression with fusion and kyphosis correction is a very
      demanding surgery and should be performed after taking into account the risks and
      benefits involved. This surgery perhaps prevents progression of neurological
      deficit and recurrence of late onset paraplegia in these complex cases in
      developing countries.

PMID- 11512074
TI  - Energy expenditure and nutritional adequacy of rehabilitation paraplegics with
      asymptomatic bacteriuria and pressure sores.
AB  - OBJECTIVE: To measure resting energy expenditure (REE) in a group of people with
      postacute paraplegia, quantify the impact of asymptomatic bacteriuria and
      pressure sore(s) on patients' metabolic rate, and estimate the adequacy of
      patients' nutritional intakes to preserve patients' protein levels. MATERIAL AND
      METHODS: Ten males with post-acute paraplegia aged 42.1+/-18.7 years. We
      evaluated: height, body mass index (BMI), resting energy expenditure (REE), total
      daily calorie requirement (E), 24-h urine creatinine excretion (Cru), creatinine
      index (CI), and nitrogen balance (NB). RESULTS: Subjects with paraplegia showed
      high erythrocyte sedimentation rates. As a group, they had normal resting calorie
      consumption when REE was normalized for unit of urine creatinine (REE/Cru), it
      was higher in patients than in controls. Six of the 10 patients had a low calorie
      intake: of these only three had a negative nitrogen balance. CONCLUSION: In
      conclusion, the resting energy expenditure of the subjects with significant
      bacteriuria and pressure sore(s) of 23.7 kcal/kg/day suggests that a large
      portion of patients may have an inadequate calorie protein intake to preserve
      their nutritional status. The clinical significance of this study is that 28.5
      kcal/kg/day may be the lower calorie threshold to meet the metabolic demands of
      people with apyretic paraplegia with bacteriuria and pressure sore(s).

PMID- 11512075
TI  - Blunt trauma to scrotum in men with spinal cord injury after they had completed
      rehabilitation in a spinal unit.
AB  - STUDY DESIGN: A report of three men with spinal cord injury (SCI) who sustained
      blunt trauma to scrotum after they had completed rehabilitation in the spinal
      unit. OBJECTIVES: To raise awareness amongst health professionals regarding: (1)
      mechanism of scrotal trauma in men with SCI (2) need for prompt assessment of
      scrotal injury (3) measures to be taken by men with SCI and their carers to
      prevent injury to the scrotum. SETTING: Regional Spinal Injuries Centre,
      Southport, England. CASE REPORTS: (1) A 31-year-old with C-6 tetraplegia
      sustained traumatic haematocele as he squashed his right testis while he jumped
      on to a toilet seat in a hurry for bowel movement. (2) A 28-year-old male with T
      7 paraplegia sat on his left testis while transferring on to a car seat. (3) A
      boxer dog jumped on to the scrotum of a 40-year-old male with T-8 paraplegia,
      while he was lying on his bed. CONCLUSIONS: Men with SCI are at high risk of
      sustaining trauma to scrotum during transfers. The scrotum may be squashed by the
      weight of the body during transfers, or the scrotum may be trapped between the
      thighs or under the torso. Men with SCI or their carers should check after each
      transfer that the scrotum is not trapped between the thighs or under the torso.
      The health professionals should encourage men with SCI to update their transfer
      skills at regular intervals in order to prevent trauma to the scrotum during
      transfers. Blunt trauma to scrotum requires prompt evaluation by ultrasonography
      so that appropriate treatment can be instituted without delay.

PMID- 11512076
TI  - Lumbar myxopapillary ependymoma mimicking neurofibroma.
AB  - OBJECTIVE: To report a case of lumbar myxopapillary ependymoma in whom
      neuroradiological and surgical findings strongly suggested neurofibroma. CLINICAL
      PRESENTATION: The patient presented with a 2 year history of progressive
      monoparesthesia and monoparesia of his right leg. He reported having minimal
      fecal and urinary incontinence. INTERVENTION: Total resection of the tumor was
      achieved by total L1-L2 laminectomies. There was no attachment to the spinal cord
      and dura. CONCLUSION: In spite of contemporary sophisticated neuroradiological
      facilities, we may still have diagnostic difficulties in some spinal tumors.

PMID- 11512078
TI  - Group B streptococcal disease: from trials and tribulations to triumph and
      trepidation.
AB  - Group B streptococci garnered attention during the 1970s when they surpassed
      Escherichia coli and Staphylococcus aureus to become the principal causes of
      sepsis in early infancy. During the 1980s, several clinical trials demonstrated
      that administration of antimicrobial agents during labor could interrupt vertical
      transmission and prevent invasive disease in the first week of life (i.e., early
      onset disease). However, prophylaxis was not widely used during the next 10
      years. On the basis of efforts by clinician-researchers, professional
      organizations, community-based parent advocacy groups, and the public health
      community, consensus recommendations for group B streptococcal prophylaxis were
      finally issued in 1996. By the end of 1999, the incidence of early-onset disease
      in selected counties within the United States had decreased by 70%, and the gap
      between black and white persons with disease narrowed by 75%. This recent triumph
      leaves the professional community treading lightly, alert to the need to monitor
      for unintended consequences that may threaten recent progress.

PMID- 11512079
TI  - Excessive antibiotic use for acute respiratory infections in the United States.
AB  - Estimating the amount and cost of excess antibiotic use in ambulatory practice
      and identifying the conditions that account for most excess use are necessary to
      guide intervention and policy decisions. Data from the 1998 National Ambulatory
      Medical Care Survey, a sample survey of United States ambulatory physician
      practices, was used to estimate primary care office visits and antibiotic
      prescription rates for acute respiratory infections. Weight-averaged antibiotic
      costs were calculated with use of 1996 prescription marketing data and adjusted
      for inflation. In 1998, an estimated 76 million primary care office visits for
      acute respiratory infections resulted in 41 million antibiotic prescriptions.
      Antibiotic prescriptions in excess of the number expected to treat bacterial
      infections amounted to 55% (22.6 million) of all antibiotics prescribed for acute
      respiratory infections, at a cost of approximately $726 million. Upper
      respiratory tract infections (not otherwise specified), pharyngitis, and
      bronchitis were the conditions associated with the greatest amount of excess use.
      This study documents that the amount and cost of excessive antibiotic use for
      acute respiratory infections by primary care physicians are substantial and
      establishes potential target rates for antibiotic treatment of selected
      conditions.

PMID- 11512080
TI  - Human herpesvirus 6 reactivation and encephalitis in allogeneic bone marrow
      transplant recipients.
AB  - To determine whether receipt of an investigational anti-CD3 monoclonal antibody
      (BC3) increased the risk of human herpesvirus 6 (HHV-6) reactivation and
      development of encephalitis in bone marrow transplant (BMT) recipients, persons
      who had and had not received BC3 were compared. Odds of HHV-6 reactivation were
      higher among BC3 recipients than among control patients (odds ratio, 2.5; 95%
      confidence interval [CI], 1.3-4.7). In addition, BC3 recipients were more likely
      than control patients to develop encephalitis (risk ratio [RR], 3.5; 95% CI, 1.3
      9.5), and this association followed a BC3 dose-dependent relationship (P=.03, by
      Mantel-Haenszel chi(2) test). In a multivariable model, HHV-6 reactivation and
      receipt of BC3 were associated with increased risk of encephalitis (RR, 5.4; 95%
      CI, 1.9-15.3, and RR, 3.3; 95% CI, 1.2-9.1, respectively). In conclusion, both
      HHV-6 reactivation and receipt of BC3 for prophylaxis of acute graft-versus-host
      disease independently increased the risk of encephalitis in allogeneic BMT
      recipients. Prospective studies to better define the relationship between HHV-6
      reactivation and encephalitis in allogeneic BMT recipients are warranted.

PMID- 11512081
TI  - Bartonellosis (Carrion's disease) in the modern era.
AB  - Bartonellosis remains a major problem in Peru, but many contemporary aspects of
      this disease have not been adequately described. We examined the cases of 145
      symptomatic patients in Lima, Peru, in whom bartonellosis was diagnosed from 1969
      through 1992, including 68 patients in the acute (hematic) phase and 77 patients
      in the eruptive (verruga) phase. In modern Peru, symptomatic patients who have
      acute-phase bartonellosis typically present with a febrile illness and systemic
      symptoms caused by profound anemia; most patients respond successfully to
      treatment with chloramphenicol. Patients who have eruptive-phase bartonellosis
      most often present with cutaneous verrugas but may have less specific symptoms,
      such as fever and arthralgias; diagnosis can be confirmed in such patients by
      Western immunoblotting, and most patients appear to respond to treatment with
      rifampin.

PMID- 11512082
TI  - Persistence of immunoglobulin M or immunoglobulin G antibody responses to
      Borrelia burgdorferi 10-20 years after active Lyme disease.
AB  - The interpretation of serological results for patients who had Lyme disease many
      years ago is not well defined. We studied the serological status of 79 patients
      who had had Lyme disease 10-20 years ago and did not currently have signs or
      symptoms of active Lyme disease. Of the 40 patients who had had early Lyme
      disease alone, 4 (10%) currently had IgM responses to Borrelia burgdorferi, and
      10 (25%) still had IgG reactivity to the spirochete, as determined by a 2-test
      approach (enzyme-linked immunosorbent assay and Western blot). Of the 39 patients
      who had had Lyme arthritis, 6 (15%) currently had IgM responses and 24 (62%)
      still had IgG reactivity to the spirochete. IgM or IgG antibody responses to B.
      burgdorferi may persist for 10-20 years, but these responses are not indicative
      of active infection.

PMID- 11512083
TI  - Clostridium difficile infection in patients with neutropenia.
AB  - Clostridium difficile is the most important cause of nosocomial infectious
      diarrhea. The importance of C. difficile-associated diarrhea (CDAD) has been
      poorly investigated in patients with neutropenia who have hematologic
      malignancies. A retrospective chart review of all patients treated in the
      leukemia ward of a university medical center during 1991-2000 determined that 875
      courses of myelosuppressive chemotherapy were administered. CDAD occurred in 7.0%
      of all cycles. In 8.2% of the patients, severe enterocolitis developed. Two
      patients died while they had diarrhea. However, in no patient was C. difficile
      infection clinically considered to be the primary cause of death. The response
      rate to oral metronidazole was 90.9%. These data indicate that C. difficile
      infection is not rare and should be suspected whenever a hospitalized patient
      with neutropenia develops diarrhea. Oral metronidazole can be recommended as
      initial drug of choice for treatment of patients with neutropenia who have
      hematologic malignancies and CDAD.

PMID- 11512084
TI  - Respiratory syncytial virus infections in previously healthy working adults.
AB  - During 1975-1995, a total of 2960 healthy adults, 18-60 years of age, were
      prospectively evaluated for respiratory virus infections. Of these subjects, 211
      (7%) acquired respiratory syncytial virus (RSV) infection. The infections were
      symptomatic in 84% of subjects, involved only the upper respiratory tract in 74%,
      and included lower respiratory tract symptoms in 26%. Overall, 40% of the
      subjects were febrile. Lower respiratory tract signs developed in 26%. RSV
      illnesses were more prolonged than non-RSV respiratory illnesses. Compared with
      influenza, RSV infections were less frequently associated with fever and
      headache, but were associated significantly more often with nasal congestion, ear
      and sinus involvement, and productive cough. Absence from work during the acute
      phase of the illness resulted from 38% of RSV infections and 66% of influenza
      cases. The mean duration of RSV illness (9.5 days), however, was significantly
      longer than that of influenza (6.8 days). The occurrence of annual epidemics of
      RSV, the virus' potential to reinfect all age groups, and the morbidity
      associated with these reinfections suggest that RSV infections in working adults
      may result in appreciable costs for medical visits and absence from work.

PMID- 11512085
TI  - Clinical outcomes of bacteremic pneumococcal pneumonia in the era of antibiotic
      resistance.
AB  - Limited data are available about the impact of antimicrobial resistance on
      clinical outcomes in cases of pneumococcal pneumonia. This was studied in 146
      persons hospitalized with invasive pneumonia due to Streptococcus pneumoniae
      (minimum inhibitory concentration of cefotaxime, > or = .25 microg/mL) who were
      identified through population-based active surveillance for the period of
      November 1994 through April 1996. Compared with matched control subjects who had
      infection with more-susceptible S. pneumoniae, the proportion of subjects who
      died or who were admitted to an intensive care unit did not differ significantly.
      Multivariable analysis showed no significant contribution of antimicrobial
      resistance to mortality or the requirement for care in an intensive care unit.
      The ability to detect an effect of antimicrobial resistance on these important
      outcome measures may have been influenced by aggressive multidrug empirical
      therapy in this group of hospitalized patients. Factors other than resistance,
      such as severity of illness at presentation and advance directive status ("do not
      resuscitate" orders), appear to have a stronger influence on pneumococcal
      pneumonia outcomes.

PMID- 11512086
TI  - Rheumatic fever in the 21st century.
AB  - In the first half of the twentieth century, the group A streptococcus (GAS) was
      established as the sole etiologic agent of acute rheumatic fever (ARF). In the
      century's latter half, the clinical importance of variation in the virulence of
      strains of GAS has become clearer. Although still obscure, the pathogenesis of
      ARF requires primary infection of the throat by highly virulent GAS strains.
      These contain very large hyaluronate capsules and M protein molecules. The latter
      contain epitopes that are cross-reactive with host tissues and also contain
      superantigenic toxic moieties. In settings where ARF has become rare, GAS
      pharyngitis continues to be common, although it is caused by GAS strains of
      relatively lower virulence. These strains, however, colonize the throat avidly
      and stubbornly. Molecularly distinct pyoderma strains may cause acute
      glomerulonephritis, but they are not rheumatogenic, even though they may
      secondarily colonize and infect the throat. Guidelines for the diagnosis,
      treatment, and prevention of GAS pharyngitis and ARF are reviewed with particular
      reference to the prevalence of the latter in the community.

PMID- 11512087
TI  - Infectious diseases journals on the World Wide Web: attractions and limitations.
AB  - Online infectious diseases (ID) journals are an increasingly common Web
      phenomenon. We performed a study of practices in this evolving area that make
      these sites more usable and useful from the perspective of ID physicians. The Web
      sites of 18 journals pertaining to general ID and infection control and hospital
      epidemiology were evaluated for a set of 24 Web interface characteristics and
      online features. Journals hosted by the High Wire Press (Antimicrobial Agents and
      Chemotherapy, Infection and Immunity, and the Journal of Antimicrobial
      Chemotherapy) and the University of Chicago Press (The Journal of Infectious
      Diseases and Clinical Infectious Diseases) best fulfilled our criteria.
      Electronic reference linking, archives, e-mail alerts, and links to external
      resources are some of the features of electronic journals that users in the ID
      specialty may find especially useful.

PMID- 11512088
TI  - Human herpesvirus 6.
AB  - The development of techniques for the culture of lymphoid cells and the isolation
      of viruses that infect these cells led to the discovery of human herpesvirus
      (HHV) 6 in 1986. At the time, HHV-6 was the first new human herpesvirus to be
      discovered in roughly a quarter of a century, and its isolation marked the
      beginning of an era of discovery in herpesvirology, with the identification of
      HHV-7 and HHV-8 (Kaposi's sarcoma-associated herpesvirus) during the following
      decade. Like most human herpesviruses, HHV-6 is ubiquitous and capable of
      establishing a lifelong, latent infection of its host. HHV-6 is particularly
      efficient at infecting infants and young children, and primary infection with the
      virus is associated with roseola infantum (exanthem subitum) and, most commonly,
      an undifferentiated febrile illness. Viral reactivation in the immunocompromised
      host has been linked to a variety of diseases, including encephalitis, and HHV-6
      has been tentatively associated with multiple sclerosis. This article discusses
      the major properties of HHV-6, its association with human disease, and the
      pathobiological significance of viral reactivation.

PMID- 11512089
TI  - Laboratory diagnosis of mycobacterial infections: new tools and lessons learned.
AB  - Even in the 21st century, tuberculosis continues to be a problem. Although the
      number of cases continues gradually to decrease in the United States, cases get
      more difficult to treat, specifically those that are multiple-drug resistant.
      Infection of one-third of the world's population ensures that tuberculosis will
      not disappear in the near future. In light of this, it will be useful to know the
      goals for the health care system and how these goals may be accomplished.
      Laboratory testing in the mycobacteriology field is experiencing more changes
      today than ever before. Determining what assays will be most useful to the
      clinician is a challenge, and acceptance of the new technology by the medical
      community an even greater one. Clinicians must use the best available resources
      to determine the most appropriate care for their patients and work together with
      the laboratory to ensure that the communication channels are open. This review
      focuses on current state-of-the-art resources useful for accurate and rapid
      laboratory diagnosis of mycobacterial infections.

PMID- 11512090
TI  - Management of psychiatric disorders in patients infected with human
      immunodeficiency virus.
AB  - Psychiatric disorders increase the risk of acquiring human immunodeficiency virus
      (HIV) and increase morbidity from HIV-related illness by impeding treatment. The
      response to highly active antiretroviral therapies is impaired by poor patient
      adherence, a substantial component of which is related to mental illness and
      substance use disorders. The recognition of psychiatric disorders in most HIV
      clinics is an issue of utmost importance. We outline diagnostic and treatment
      issues for major depression, bipolar disorder, personality disorder, substance
      use disorders, and demoralization as seen in patients with HIV. Our experience at
      the Johns Hopkins Moore (HIV) Clinic has led us to conclude that treatment of
      these disorders greatly improves patient adherence to treatment and outcomes of
      HIV infection.

PMID- 11512091
TI  - Diagnosis and treatment of androgen deficiency in human immunodeficiency virus
      infected men and women.
AB  - Androgen deficiency is a common endocrine abnormality among men and women with
      human immunodeficiency virus (HIV) infection. Low testosterone concentrations are
      associated with lower CD4 cell count, advanced stage of illness, medication use,
      and weight loss. Signs and symptoms may be nonspecific. The most useful
      laboratory indicator is the serum bioavailable (free) testosterone concentration.
      A number of different testosterone preparations for treatment of androgen
      deficiency in HIV-infected men now exist. Administration of im testosterone
      significantly increases weight and lean body mass, energy, quality of life, and
      depression scores in HIV-infected men with low testosterone levels. Newer
      transdermal and gel preparations provide more-consistent steady-state dosing but
      are not as well tested, and sufficient testosterone concentrations may not be
      achieved with their use. Androgen deficiency is also common among HIV-infected
      women. Preliminary studies suggest that use of physiological testosterone
      administration, to achieve testosterone levels within the normal range, is of
      benefit in HIV-infected women, but further studies are necessary to define the
      therapeutic role of androgen therapy in this population.

PMID- 11512092
TI  - Strategies for optimizing adherence to highly active antiretroviral therapy:
      lessons from research and clinical practice.
AB  - Successful treatment of human immunodeficiency virus infection/acquired
      immunodeficiency syndrome (HIV/AIDS) with highly active antiretroviral therapy
      (HAART) requires that patients maintain nearly perfect adherence to the
      prescribed regimen. Suboptimal adherence to antiretroviral therapy is clearly the
      most common cause of virologic failure of HAART regimens. Given the critical role
      of adherence in successful antiretroviral therapy, it is essential that providers
      of care for patients with HIV infection have a strategy that proactively assists
      and supports their patients' efforts to adhere to medication regimens. This
      review endeavors to provide a clinically focused approach to optimizing adherence
      of patients to HAART.

PMID- 11512093
TI  - Human immunodeficiency virus pathogenesis: insights from studies of lymphoid
      cells and tissues.
AB  - Although plasma virus load is invaluable for monitoring human immunodeficiency
      virus (HIV) infection, key pathogenesis events and most viral replication take
      place in lymphoid tissues. Decreases in virus load associated with therapy occur
      in plasma and tissues, but persistent latent infection and ongoing viral
      replication are evident. Many unanswered questions remain regarding mechanisms of
      HIV-associated lymphocyte depletion, but partial CD4(+) cell reconstitution after
      therapy likely reflects retrafficking from inflamed tissues, increased thymic or
      peripheral production, and decreased destruction. Rapid establishment of latent
      infection and the follicular dendritic cell-associated viral pool within lymphoid
      tissues suggest that only early intervention could substantially alter the
      natural history of HIV. If therapy is started prior to seroconversion, some
      individuals retain potent HIV-specific cellular immune responsiveness that is
      suggestive of delayed progression. Although complete virus eradication appears
      out of reach at present, more attention is being directed toward the prospect of
      boosting HIV-specific immune responses to effect another type of "clinical cure":
      immune-mediated virus suppression in the absence of therapy.

PMID- 11512094
TI  - Herpes simplex virus shedding and plasma human immunodeficiency virus RNA levels
      in coinfected women.
AB  - Asymptomatic herpes simplex virus (HSV) shedding was described in a cohort of
      human immunodeficiency virus (HIV)-infected women, and the association of HSV
      shedding with changes in plasma HIV RNA load was investigated. Genital, rectal,
      and oral swabs were obtained daily during a 4-week period for polymerase chain
      reaction and culture, and concomitant plasma specimens were drawn 3 times weekly
      for determination of HIV RNA load. During the study, 70% and 79% of subjects shed
      HSV from the oral cavity and genital area, respectively. Shedding of HSV occurred
      for a mean of 3.2 days for oral shedding and 5.4 days for genital shedding. Mean
      plasma HIV RNA loads during periods of HSV shedding and nonshedding and for
      periods 3 days after the cessation of shedding were compared; no significant
      differences were found (P=.74). In women who shed HSV, as evaluated by detection
      of virus, plasma HIV RNA load did not fluctuate with HSV shedding.

PMID- 11512095
TI  - Successful percutaneous dihydrotestosterone treatment of gynecomastia occurring
      during highly active antiretroviral therapy: four cases and a review of the
      literature.
AB  - Fourteen cases of gynecomastia occurring during highly active antiretroviral
      therapy (HAART) have been reported in the literature. To date, no specific
      therapeutic approach has been proposed, and gynecomastia has usually persisted.
      We report 4 new cases of HAART-induced gynecomastia that were successfully
      treated with percutaneous dihydrotestosterone gel.

PMID- 11512096
TI  - Association between bacterial vaginosis and expression of human immunodeficiency
      virus type 1 RNA in the female genital tract.
AB  - We assessed the effect of lower genital tract infections on human
      immunodeficiency virus type 1 (HIV-1) RNA shedding in the female genital tract.
      Bacterial vaginosis was significantly associated with HIV-1 RNA expression in the
      female genital tract of HIV-infected women.

PMID- 11512097
TI  - Campylobacter jejuni enteritis.
AB  - We report the development of Campylobacter jejuni enteritis in a patient with
      preexisting humoral and cellular immune recognition of C. jejuni antigens. This
      is one of few studies in which the immunologic status of a person with regard to
      C. jejuni before and after C. jejuni infection is directly compared, and it is
      the only study of which we are aware that includes measurements of cellular
      immunity. The findings may be important to Campylobacter vaccine development
      efforts.

PMID- 11512098
TI  - Arthus reaction to recombinant hepatitis B virus vaccine.
AB  - A severe, local, inflammatory, late-phase reaction accompanied by skin necrosis
      occurred after an infant was given an intramuscular injection of recombinant
      hepatitis B virus vaccine. The clinical course and appearance of the rash were
      typical of an Arthus reaction. Although not identical to this case, prior
      reported cases of complement-mediated reactions occurring after hepatitis B virus
      infection or vaccination provide theoretical support for this diagnosis.

PMID- 11512100
TI  - Probable atypical cat scratch disease presenting as isolated posterior pancreatic
      duodenal lymphadenitis and abdominal pain.
AB  - We report a case involving a 15-year-old girl with atypical, clinically
      unsuspected cat scratch disease (CSD) presenting as isolated posterior pancreatic
      duodenal lymphadenitis, fever, and abdominal pain. The serological, abdominal
      ultrasonographic, and CT findings, as well as clinical and epidemiological data,
      indicate that B. henselae was likely an etiologic agent of CSD in our patient.

PMID- 11512099
TI  - Rhinovirus RNA in the maxillary sinus epithelium of adult patients with acute
      sinusitis.
AB  - We used in situ hybridization for the detection of rhinovirus in maxillary sinus
      biopsy specimens obtained from 14 adult patients with acute sinusitis. In 7
      specimens, rhinovirus RNA could be demonstrated in the maxillary sinus
      epithelium, thereby confirming the etiology of rhinovirus and the clinical
      suspicion of acute sinusitis.

PMID- 11512101
TI  - Nephrotoxicity of amphotericin B desoxycholate.

PMID- 11512102
TI  - Two distinct patterns of central nervous system complications due to Mycoplasma
      pneumoniae infection.

PMID- 11512104
TI  - Clinical correlates of enterococcal bacteremia: attributable or associated?

PMID- 11512106
TI  - Simultaneous infection with multiple strains of Mycobacterium tuberculosis.
AB  - Drug-susceptible and drug-resistant isolates of Mycobacterium tuberculosis were
      recovered from 2 patients, 1 with isoniazid-resistant tuberculosis (patient 1)
      and another with multidrug-resistant tuberculosis (patient 2). An investigation
      included patient interviews, record reviews, and genotyping of isolates. Both
      patients worked in a medical-waste processing plant. Transmission from waste was
      responsible for at least the multidrug-resistant infection. We found no evidence
      that specimens were switched or that cross-contamination of cultures occurred.
      For patient 1, susceptible and isoniazid-resistant isolates, collected 15 days
      apart, had 21 and 19 restriction fragments containing IS6110, 18 of which were
      common to both. For patient 2, a single isolate contained both drug-susceptible
      and multidrug-resistant colonies, demonstrating 10 and 11 different restriction
      fragments, respectively. These observations indicate that simultaneous infections
      with multiple strains of M. tuberculosis occur in immunocompetent hosts and may
      be responsible for conflicting drug-susceptibility results, though the
      circumstances of infections in these cases may have been unusual.

PMID- 11512107
TI  - Outbreak of meningococcal disease after an influenza B epidemic at a Hellenic Air
      Force recruit training center.
AB  - In January 1996, during an outbreak of meningococcal disease at a Hellenic Air
      Force recruit center in southern Greece, we collected paired serum specimens from
      55 randomly selected recruits and tested for antibodies against influenza virus
      types A and B. Of 55 specimens, 15 (27%) were found to be positive for recent
      influenza B infection, confirming previous reports that respiratory tract
      infection due to influenza is probably a predisposing factor for meningococcal
      disease.

PMID- 11512108
TI  - Cushing's syndrome presenting as disseminated cutaneous Mycobacterium chelonae
      infection.
AB  - Mycobacterium chelonae infection has not to our knowledge been reported as a
      complication of endogenous Cushing's syndrome. We describe a patient who
      presented with sporotrichoid M. chelonae infection and olecranon bursitis whose
      symptoms did not completely resolve until after bilateral adrenalectomy.

PMID- 11512110
TI  - We're losing our identity.

PMID- 11512109
TI  - Circulating cytokines in patients with cat scratch disease.
AB  - Levels of circulating interleukin (IL)-2, IL-6, and IL-10, measured by enzyme
      linked immunosorbent assay, were significantly higher in patients with cat
      scratch disease (CSD) than in healthy control subjects; no induction of IL-12 was
      observed, and levels of interferon-gamma and IL-4 were generally not detectable.
      This is the first report showing increased circulating cytokine levels in
      patients with CSD. The induction of these mediators can partly explain some
      clinical and pathological features of the disease.

PMID- 11512111
TI  - The effect of amitriptyline on pain intensity and perception of stress in
      bruxers.
AB  - PURPOSE: The purpose of this clinical pilot study was to evaluate the effect of a
      tricyclic antidepressant, amitriptyline, on pain-intensity level and level of
      stress in bruxers. MATERIALS AND METHODS: In a randomized, double-blind,
      crossover experimental design, 10 subjects received active (amitriptyline 25
      mg/night) and inactive (placebo 25 mg/night) medication, over a period of 4
      weeks. RESULTS: The administration of amitriptyline for 4 weeks did not
      significantly (p >.05) reduce pain intensity. However, it significantly (p <.05)
      reduced the level of stress perception. CONCLUSION: The results of this limited
      study do not support the administration of small doses of amitriptyline over a
      period of 4 weeks for the management of pain resulting from sleep bruxism.
      However, the results support the administration of small doses of amitriptyline
      for the management of the perception of stress levels associated with sleep
      bruxism.

PMID- 11512112
TI  - Factors influencing optical 3D scanning of vinyl polysiloxane impression
      materials.
AB  - PURPOSE: Future growth in dental practice lies in digital imaging enhancing many
      chairside procedures and functions. This revolution requires the fast, accurate,
      and 3D digitizing of clinical records. One such clinical record is the chairside
      impression. This study investigated how surface angle and surface roughness
      affect the digitizing of vinyl polysiloxane impression materials. MATERIALS AND
      METHODS: Seventeen vinyl polysiloxane impression materials were digitized with a
      white light optical digitizing system. Each sample was digitized at 3 different
      angles: 0 degrees, 22.5 degrees, and 45 degrees, and 2 digitizer camera f-stops.
      The digitized images were rendered on a computer monitor using custom software
      developed under NIH/NIDCR grant DE12225. All the 3D images were rotated to the 0
      degrees position, cropped using Corel Photo-Paint 8 (Corel Corp, Ottawa, Ontario,
      Canada), then saved in the TIFF file format. The impression material area that
      was successfully digitized was calculated as a percentage of the total sample
      area, using Optimas 5.22 image processing software (Media Cybernetics, LP, Silver
      Spring, MD). The dependent variable was a Performance Value calculated for each
      material by averaging the percentage of area that digitized over the 3 angles.
      New samples with smooth and rough surfaces were made using the 7 impression
      materials with the largest Performance Values. These samples were tested as
      before, but with the additional angle of 60 degrees. Silky-Rock die stone (Whip
      Mix Corp, Louisville, KY) was used as a control. RESULTS: The Performance Values
      for the 17 impression materials ranged from 0% to 100%. The Performance Values
      for the 7 best materials were equivalent to the control at f/11 out to a surface
      angle of 45 degrees; however, only Examix impression material (GC America Inc,
      Alsip, IL) was equivalent to the control at f/11/?16. At the 60 degrees surface
      angle with f/11/?16, the Performance Values were 0% for all the impression
      materials, whereas that for the control was 90%. The difference in the
      Performance Values for the smooth and rough surface textures was 7%, which was
      not significant. CONCLUSIONS: The digitizing performance of vinyl polysiloxane
      impression materials is highly material and surface angle-dependent and is
      significantly lower than the die stone control when angles to 60 degrees are
      included. It is affected to a lesser extent by surface texture.

PMID- 11512113
TI  - Accuracy and pourability of gypsum preweighed packages.
AB  - PURPOSE: The purpose of this study was to determine the amount of gypsum provided
      by the manufacturers in their preweighed packages and to determine the amount of
      gypsum dispensed from the packages as a function of the method used. MATERIALS
      AND METHODS: One hundred twenty unopened packages from 8 manufacturers were
      weighed. Ten packages from each manufacturer were opened with the contents
      completely removed by tapping the packages, and the contents were weighed
      (thorough method). The other 5 packages from each manufacturer were opened,
      quickly poured, and the contents weighed (quick method). All packages were then
      slit open on all sides and completely cleaned. The cleaned packages were then
      weighed. Calculations were made to determine (1) the amount of gypsum that was
      "supplied" by the manufacturer and (2) the amount removed from the packages using
      the "quick" and "thorough" methods. The raw data was normalized to percentage of
      stated weight. A Welch analysis of variance was used to evaluate the
      heteroscedastic data at a 95% confidence level. Thereafter, a post hoc Student t
      test was used to determine if the percentages of stated weight for (1) supplied,
      (2) thorough, and (3) quick were significantly different from 100%. RESULTS: A
      statistically significant difference was found for the amount of gypsum supplied
      by the manufacturers (p <.001) and the amount of material removed from the
      packages via the 2 different methods used (p <.001). Seven of the 8
      manufacturers' preweighed packages were remarkably close to their stated weight
      for amounts "supplied" and the "thorough" method. High standard deviations from
      the mean were found for the "quick" method of gypsum removal. CONCLUSION: Within
      the limits of this study, results indicate that the use of a "thorough" method to
      remove gypsum from preweighed packages was important. Ideally, gypsum supplied in
      preweighed packages should be weighed initially to ensure an optimal water/powder
      ratio.

PMID- 11512114
TI  - Development of a nondestructive compliance test for resilient denture liners.
AB  - PURPOSE: Resilient denture liners are prescribed for patients who cannot adjust
      to hard-based dentures because of a thin mucosa or severe alveolar ridge
      resorption. A nondestructive test to evaluate compliance of new soft liner
      materials will be useful in clinical trials. The purpose of this study was to
      evaluate a nondestructive compliance testing technique designed to characterize
      long-term, silicone-based resilient denture liner materials. MATERIALS AND
      METHODS: Samples of thicknesses of 1.1, 2.2, 3.3, and 4.4 mm of 2 materials (MPDS
      SL [Lai Laboratories, Inc, Burnsville, MN] and Molloplast-B [Buffalo Dental, New
      York, NY]) were assessed for compliance using a closed-loop servohydraulic
      testing system, applying a 3 lb force following a squarewave pattern; force and
      position values were recorded using a storage oscilloscope. The oscilloscope
      values were analyzed using computer software to determine compliance values. The
      effect of material thickness was examined by testing wedges of the 2 materials.
      RESULTS: The testing technique used showed that differing thicknesses had
      significantly different compliance values (p <.0001). In the materials used to
      evaluate the technique, MPDS-SL behaved more elastically than did Molloplast-B (p
      <.0001). Material thicknesses beyond 2.2 mm did not increase compliance, although
      MPDS-SL had a steeper thickness-compliance curve than Molloplast-B. CONCLUSIONS:
      The method used to test compliance proved to be sufficiently sensitive to
      distinguish between 2 materials and between varying thicknesses. The sensitivity
      and nondestructive nature of this test show its suitability for clinical
      evaluation of resilient denture liners.

PMID- 11512115
TI  - A nontraditional technique for obtaining optimal esthetics for an immediate
      denture: a clinical report.
AB  - Bimaxillary protrusion and severe labioversion of anterior teeth complicate
      impression procedures and increase the difficulty in making esthetic predictions
      for the immediate complete denture patient. The presented technique, performed in
      reverse order of traditional methods, is accomplished in stages in which the
      anterior and nonessential posterior teeth are extracted and interim removable
      partial dentures placed. An opportunity is thus created to evaluate esthetics,
      phonetics, and anterior tooth function before extraction of the remaining
      dentition and delivery of immediate complete dentures. This technique facilitated
      the determination of the need for alveoplasty of the anterior maxilla.

PMID- 11512116
TI  - Discoloration of a titanium alloy removable partial denture: a clinical report.
AB  - With recent advances in dental technology, titanium is currently used for
      fabrication of crowns, fixed partial dentures, implant frameworks, and removable
      partial denture frameworks. The use of titanium-aluminum-vanadium (Ti-6Al-4V)
      alloy assumes that it imparts similar anti-corrosion characteristics to the
      commercially pure titanium. This clinical report describes a patient who
      experienced discoloration of a Ti-6Al-4V alloy removable partial denture.

PMID- 11512117
TI  - A clinical report about an unusual occurrence of post-anesthetic tongue swelling.
AB  - Dentures are routinely removed from the oral cavity before general anesthetic
      procedures. They are only reinserted much later when the patient returns to the
      room. This clinical report describes an edentulous patient who developed acute
      tongue swelling from venous congestion as a result of tongue recovery from
      general anesthesia. Her complete dentures were used to separate the residual
      ridges during the recovery period and relieved the congestion. Denture insertion
      increased the height and volume of the oral cavity, which reduced pressure on the
      tongue, preventing a cycle of tongue compression, congestion, and swelling. This
      unusual complication suggests that it may be prudent for the edentulous patient
      to be accompanied by their dentures in the perioperative period.

PMID- 11512118
TI  - Conversion of an implant radiographic template into a surgical template.
AB  - A method is presented for converting a radiographic template into a surgical
      template using the information acquired from the analysis of tomograms. Necessary
      changes of the implant position and angulation are transferred to the indexed and
      sectioned cast. Realignment of the initial template with the correct position
      allows its modification into a surgical template.

PMID- 11512119
TI  - The history of articulators: Pursuing the evolution of the incisal-pin and guide,
      part II.

PMID- 11512120
TI  - The patients are coming!

PMID- 11512125
TI  - Dose staggering as a strategy to reduce drug--drug interactions due to reversible
      enzyme inhibition between orally administered drugs with high first pass effect:
      a computer simulation study.
AB  - A physiological computer model was designed to simulate the metabolic drug-drug
      interactions between two orally co-administered drugs due to reversible enzyme
      inhibition using drug concentrations in the portal vein. The extent of
      interactions was compared at steady-state for the effects of a delay in time
      between the administration of the substrate and the inhibitor. It was
      demonstrated that the extent of the interactions can be strongly affected by a
      time interval between the two drug administrations. By delaying the
      administration of the inhibitor until after the absorption phase of the
      substrate, one can significantly reduce the extent of the drug--drug
      interactions. This is because drug concentrations in the portal vein and the
      liver are much higher than that in the systemic circulation during the absorption
      phase. The model also showed that interactions involving substrates with a high
      extraction ratio (E(H)), i.e., drugs with higher first-pass effect, can be more
      strongly affected by dose staggering. Substrates with a low absorption rate
      constant (k(a)) require a longer interval with the inhibitor in order to reduce
      the extent of the interactions. This observation suggests dose staggering as a
      simple and cost-effective way to reduce the extent of unwanted drug--drug
      interactions in clinical practice.

PMID- 11512126
TI  - Theoretical pharmacokinetic and pharmacodynamic simulations of drug delivery
      mediated by blood--brain barrier transporters.
AB  - Pharmacokinetic/pharmacodynamic simulations were performed to assess the
      feasibility of central nervous system (CNS) drug delivery via endogenous
      transporters resident at the blood-brain barrier (BBB). Pharmacokinetic models
      were derived for intravenous bolus dosing of a hypothetical drug in the absence
      or presence of an endogenous, competing transport inhibitor. These models were
      linked to CNS pharmacodynamic models where the effect sites were either cell
      surface receptors or intracellularly localized enzymes. The response of the
      dependent parameter, the duration of effect (t(dur)), was examined in
      relationship to changes in the independent parameters, i.e. dose, elimination
      rate constant (k(e1)), BBB transport parameters (K(m1) and V(max1)) and EC(50)
      (effective concentration that elicits a 50% response). As expected, t(dur)
      increased with (a) increases in drug doses, (b) decreases in k(e1) or (c)
      decreases in EC(50), irrespective of the effect site. Surprisingly, endogenous
      transport inhibition produced decreases in drug terminal half-life and
      corresponding decreases in t(dur). Interestingly, t(dur) was independent of
      assigned transporter K(m) and V(max) when the dose/EC(50) ratio (dose/EC(50)) was
      >1 (irrespective of endogenous transport inhibition), but highly dependent on
      K(m1) and V(max1) when dose/EC(50) was (a) <1 (no endogenous transport
      inhibition) or (b) equal to 1 (with endogenous transport inhibition). Oral input
      of the endogenous transport inhibitor produced a decrease in t(dur) when the
      dose/EC(50) range was 0.1-10. These simulations highlight that (a) systemic
      pharmacokinetic and BBB transport parameters influence t(dur), (b) drug terminal
      half-life is inversely related to circulating levels of endogenous inhibitors,
      and (c) oral ingestion of endogenous transport inhibitor(s) reduces t(dur).
      Overall, these simulations provide insight for the feasibility of rational CNS
      drug design/delivery via endogenous transporters.

PMID- 11512127
TI  - Dose-dependent pharmacokinetics of a new neuroprotective agent for ischemia
      reperfusion damage, KR-31378, in rats.
AB  - The dose-dependent pharmacokinetic parameters of a new neuroprotective agent for
      ischemia-reperfusion damage, KR-31378, were evaluated after intravenous and oral
      administration, 10, 20, and 50 mg/kg, to rats. After intravenous administration
      of 50 mg/kg, the dose-normalized (10 mg/kg) AUC (994 microg min/mL) was
      significantly greater than that at 10 (569 microg min/ml) and 20 (660 microg
      min/mL) mg/kg. This could be due to slower clearance (Cl) with increasing dosage
      (18.5, 14.6, and 10.2 mL/min/kg for 10, 20, and 50 mg/kg, respectively). The
      slower Cl with increasing dosage could be due to saturable metabolism of KR-31378
      in rats and this could be supported by significantly slower Cl(nr) and
      significantly greater 24-h urinary excretion of the drug at 50 mg/kg than those
      at 10 and 20 mg/kg. After oral administration of 50 mg/kg, the dose-normalized
      (10 mg/kg) AUC (1160 microg min/mL) was significantly greater than that at 10
      (572 microg min/mL) and 20 (786 microg min/mL) mg/kg. Note that the AUCs were
      comparable (not significantly different) between intravenous and oral
      administration at each dosage, indicating that the absorption from
      gastrointestinal tract was almost complete and the first-pass (gastric,
      intestinal, and hepatic) effect was not considerable after oral administration to
      rats.

PMID- 11512128
TI  - Factors influencing the protein binding of a new phosphodiesterase V inhibitor,
      DA-8159, using an equilibrium dialysis technique.
AB  - Various factors influencing the protein binding of DA-8159 to 4% human serum
      albumin (HSA) were evaluated using an equilibrium dialysis technique at an
      initial DA-8159 concentration of 5 microg/mL. It took approximately 8 h
      incubation to reach an equilibrium between 4% HSA and an isotonic phosphate
      buffer of pH 7.4 containing 3% of dextran ('the buffer') using a Spectra/Por 2
      membrane (mol. wt. cut-off: 12,000--14,000) in a water bath shaker kept at 37
      degrees C and at a rate of 50 oscillations per min. The extent of binding was
      dependent on DA-8159 concentrations, HSA concentrations, incubation temperature,
      buffer pH, and alpha-1-acid glycoprotein (AAG) concentrations. The binding of DA
      8159 in heparinized human plasma (93.9%) was significantly higher than in rats
      (81.4%), rabbits (80.4%), and dogs (82.2%), and this could be due to differences
      in AAG concentrations in plasma.

PMID- 11512129
TI  - Group comparisons involving missing data in clinical trials: a comparison of
      estimates and power (size) for some simple approaches.
AB  - When using 'intent-to-treat' approaches to compare outcomes between groups in
      clinical trials, analysts face a decision regarding how to account for missing
      observations. Most model-based approaches can be summarized as a process whereby
      the analyst makes assumptions about the distribution of the missing data in an
      attempt to obtain unbiased estimates that are based on functions of the observed
      data. Although pointed out by Rubin as often leading to biased estimates of
      variances, an alternative approach that continues to appear in the applied
      literature is to use fixed-value imputation of means for missing observations.
      The purpose of this paper is to provide illustrations of how several fixed-value
      mean imputation schemes can be formulated in terms of general linear models that
      characterize the means of distributions of missing observations in terms of the
      means of the distributions of observed data. We show that several fixed-value
      imputation strategies will result in estimated intervention effects that
      correspond to maximum likelihood estimates obtained under analogous assumptions.
      If the missing data process has been correctly characterized, hypothesis tests
      based on variances estimated using maximum likelihood techniques asymptotically
      have the correct size. In contrast, hypothesis tests performed using the
      uncorrected variance, obtained by applying standard complete data formula to
      singly imputed data, can provide either conservative or anticonservative results.
      Surprisingly, under several non-ignorable non-response scenarios, maximum
      likelihood based analyses can yield equivalent hypothesis tests to those obtained
      when analysing only the observed data.

PMID- 11512130
TI  - An evaluation of phase I clinical trial designs in the continuous dose-response
      setting.
AB  - Both traditional phase I designs and the increasingly popular continual
      reassessment method (CRM) designs select an estimate of maximum tolerable dose
      (MTD) from among a set of prespecified dose levels. Although CRM designs use an
      implied dose-response model to select the next dose level, in general it is
      neither assumed nor necessary that this model be tied to the actual dose of a
      drug. In contrast, in our two-stage design the fitting of a dose-response model
      after data have been collected is a necessary feature of the design, and the MTD
      is not constrained to be one of the prespecified dose levels. We conducted a
      simulation study to evaluate the performance of the two-stage design, two
      likelihood-based CRM designs, and two traditional designs in estimating the MTD
      in situations where one assumes that an explicit dose-response model exists.
      Under a wide variety of dose-response settings, we examined the bias and
      precision of estimates, and the fraction of estimates that were extremely high or
      low. We also studied the effect of adding a model fitting step at the end of a
      traditional design or a CRM design. The best performance was achieved using the
      two-stage and CRM designs. Although the CRM designs generally had smaller bias,
      the two-stage design yielded equal or somewhat smaller precision in some cases.
      The addition of a model-fitting step slightly improved the precision of the CRM
      estimates and decreased the percentage of extreme estimates. Allowing
      interpolation between doses for updating during CRM did not improve overall
      performance.

PMID- 11512132
TI  - Data augmentation priors for Bayesian and semi-Bayes analyses of conditional
      logistic and proportional-hazards regression.
AB  - Data augmentation priors have a long history in Bayesian data analysis. Formulae
      for such priors have been derived for generalized linear models, but their
      accuracy depends on two approximation steps. This note presents a method for
      using offsets as well as scaling factors to improve the accuracy of the
      approximations in logistic regression. This method produces an exceptionally
      simple form of data augmentation that allows it to be used with any standard
      package for conditional-logistic or proportional-hazards regression to perform
      Bayesian and semi-Bayes analyses of matched and survival data. The method is
      illustrated with an analysis of a matched case-control study of diet and breast
      cancer.

PMID- 11512131
TI  - Optimal estimation of transposition rates of insertion sequences for molecular
      epidemiology.
AB  - Outbreaks of infectious disease can be confirmed by identifying clusters of DNA
      fingerprints among bacterial isolates from infected individuals. This procedure
      makes assumptions about the underlying properties of the genetic marker used for
      fingerprinting. In particular, it requires that each fingerprint changes
      sufficiently slowly within an individual that isolates from separate individuals
      infected by the same strain will exhibit similar or identical fingerprints. We
      propose a model for the probability that an individual's fingerprint will change
      over a given period of time. We use this model together with published data in
      order to estimate the fingerprint change rate for IS6110 in human tuberculosis,
      obtaining a value of 0.0139 changes per copy per year. Although we focus on
      insertion sequences (IS), our method applies to other fingerprinting techniques
      such as pulsed-field gel electrophoresis (PFGE). We suggest sampling intervals
      that produce the least error in estimates of the fingerprint change rate, as well
      as sample sizes that achieve specified levels of error in the estimate.

PMID- 11512133
TI  - Phase specific analysis of herpes zoster associated pain data: a new statistical
      approach.
AB  - Herpes zoster or shingles is a frequent occurrence in both elderly individuals
      and immunocompromised hosts. The pain associated with herpes zoster is the most
      debilitating complication of the disease. It can be described as acute pain and
      post-herpetic neuralgia or zoster associated pain (ZAP). The latter definition
      encompasses pain from the onset of disease through its resolution and provides a
      convenient analytic tool for evaluation of antiviral therapy. A heuristic
      examination of ZAP historical data suggests the existence of three phases of pain
      resolution: the acute, subacute and chronic phases. The subacute and chronic
      phases comprise the post-herpetic neuralgia (PHN) stage. Common analytic methods,
      such as a Kaplan-Meier survival function or a Cox's model, have been used to
      assess the pain. However, such approaches do not adequately allow for phase
      comparison. Notably, in the clinical trial setting the comparison of specific
      treatment effects on the latter stages of pain are of the greatest medical
      relevance since this is the most debilitating phase of the illness. In order to
      incorporate the phase-specific information in the modelling of time to cessation
      of ZAP, we assumed the hazard function was a stepwise constant. Utilizing the
      full likelihood function, we obtained the maximum likelihood estimate for the
      transition times (that is, change-points), and other parameters of medical
      importance. The standard error of the change-point estimates were obtained
      through a bootstrapping method. The asymptotic properties of the parameter
      estimates are also discussed. Hence, the rates of pain resolution across all
      phases can be examined in order to precisely define the existence of multiple
      phases. In addition, the covariates effect can be examined across phases and
      populations, thereby allowing us to translate potential efficacy of a standard
      therapy to different populations. These results can be utilized in the design of
      clinical trials or in targeting the outcome for a specific phase while
      controlling for the effect of other variables.

PMID- 11512134
TI  - Effects of covariance model assumptions on hypothesis tests for repeated
      measurements: analysis of ovarian hormone data and pituitary-pteryomaxillary
      distance data.
AB  - In the analysis of repeated measurements, multivariate methods which account for
      the correlations among the observations from the same experimental unit are
      widely used. Two commonly-used multivariate methods are the unstructured
      multivariate approach and the mixed model approach. The unstructured multivariate
      approach uses MANOVA types of models and does not require assumptions on the
      covariance structure. The mixed model approach uses multivariate linear models
      with random effects and requires covariance structure assumptions. In this paper,
      we describe the characteristics of tests based on these two methods of analysis
      and investigate the performance of these tests. We focus particularly on tests
      for group effects and parallelism of response profiles.

PMID- 11512135
TI  - Parametric modelling of neonatal mortality in relation to size at birth.
AB  - We use a richly parameterized model to analyse the effects of shortness and
      thinness at birth on neonatal mortality in Swedish live-born singletons. The
      model captures the hazard of neonatal mortality according to the function alpha x
      exp(-gamma x t) + delta, where t represents age. Covariates are allowed to
      simultaneously influence the initial excess hazard, the rate of decay, and the
      long-term hazard. Among term newborns, birth length for gestational age had a
      stronger effect on the long-term hazard and a weaker effect on the initial excess
      hazard than the Ponderal index. The initial excess hazard associated with a low
      Ponderal index tended to decay quickly. Among preterm newborns, a higher birth
      length for gestational age was associated with lower initial and long-term
      hazards, and with a faster rate of decay of the initial excess hazard. In
      contrast, the Ponderal index was not associated with the long-term hazard. We
      discuss the interpretability of the model and its potential use in neonatology
      and medical demography. We also compare the model to a Cox model with time
      dependent covariates.

PMID- 11512136
TI  - Optimal design for linear interpolation of curves.
AB  - Non-parametric procedures are often used for the analysis of pharmacokinetic
      trials. Fewer design procedures are available for non-parametric estimation than
      for parametric estimation. Linear interpolation is widely used for curve
      estimation in pharmacokinetic trials, where often only sparse sampling is
      feasible. Current design procedures for smoothing or local fit are not suitable
      as they are based on asymptotic properties and the bias of the estimate is
      ignored. This paper proposes optimal designs that minimize the mean squared error
      of linear interpolation. Optimal designs for three situations are considered. The
      first situation is single curve estimation based on an ordinary non-linear model.
      The second is estimating several curves in a non-linear mixed model setting using
      an average mean squared error as the design criterion. The third situation is
      destructive sampling where estimating the average curve is the main purpose. In
      the first situation, the design results in the best linear interpolation when the
      variance is constant. For the destructive sampling design, an algorithm based on
      approximations is proposed. This algorithm can be programmed in a common
      statistical package. Numerical examples are used to illustrate the design
      procedure.

PMID- 11512137
TI  - A general goodness-of-fit approach for inference procedures concerning the kappa
      statistic.
AB  - The kappa statistic is frequently used as a measure of agreement among two or
      more raters. Although considerable research on statistical inferences for this
      statistic has been published for the case of two raters and a binary outcome,
      relatively little work has appeared on inference problems for the case of
      multiple raters and/or polytomous nominal outcome categories. In this paper we
      propose a new procedure for constructing inferences for the kappa statistic that
      may be applied to this general case. The procedure is based on a chi-square
      goodness-of-fit test as applied to the Dirichlet multinomial model, and is a
      natural extension of previously proposed procedures that apply to more restricted
      cases. A simulation study shows that the new procedure provides confidence
      interval coverage levels and type I error rates close to nominal over a wide
      range of parameter combinations. We also present a sample size formula which may
      be used to determine the required number of subjects and raters for a given
      number of outcome categories.

PMID- 11512138
TI  - Improving the fit of bivariate smoothing splines when estimating longitudinal
      immunological and virological markers in HIV patients with individual
      antiretroviral treatment strategies.
AB  - CD4+ lymphocyte count and HIV RNA plasma viral load are longitudinally monitored
      in patients with HIV infection. Because data collection intervals may be
      unequally spaced and these markers experience high within-patient variability,
      they may be smoothed before use in subsequent models. Estimation strategies must
      be able to accommodate the drastic changes in viral load which may occur when an
      individual's treatment strategy is updated. Because these treatment changes are
      not regimented, these dynamics cannot be modelled using standard methods. We
      propose univariate and bivariate cubic smoothing splines to fit CD4+ count and
      viral load over time. The method is developed using state space equations, and
      the Kalman filter is used to calculate the log-likelihood. Non-linear
      optimization is used to obtain the maximum likelihood estimates. A modification
      of the Kalman filter allows non-informative or diffuse priors at the initial
      observation. Since treatment changes are expected to alter the shape of the
      curve, we further extend the Kalman filter to permit greater flexibility in the
      smoothing spline at these time points. The method produces smoothed estimates of
      the viral load and CD4+ count curves over time.

PMID- 11512139
TI  - Using observational data to estimate prognosis: an example using a coronary
      artery disease registry.
AB  - With the proliferation of clinical data registries and the rising expense of
      clinical trials, observational data sources are increasingly providing evidence
      for clinical decision making. These data are viewed as complementary to
      randomized clinical trials (RCT). While not as rigorous a methodological design,
      observational studies yield important information about effectiveness of
      treatment, as compared with the efficacy results of RCTs. In addition, these
      studies often have the advantage of providing longer-term follow-up, beyond that
      of clinical trials. Hence, they are useful for assessing and comparing patients'
      long-term prognosis under different treatment strategies. For patients with
      coronary artery disease, many observational comparisons have focused on medical
      therapy versus interventional procedures. In addition to the well-studied problem
      of treatment selection bias (which is not the focus of the present study), three
      significant methodological problems must be addressed in the analysis of these
      data: (i) designation of the therapeutic arms in the presence of early deaths,
      withdrawals, and treatment cross-overs; (ii) identification of an equitable
      starting point for attributing survival time; (iii) site to site variability in
      short-term mortality. This paper discusses these issues and suggests strategies
      to deal with them. A proposed methodology is developed, applied and evaluated on
      a large observational database that has long-term follow-up on nearly 10 000
      patients.

PMID- 11512140
TI  - Thiols enhance the sensitivity of luminescent assays for non-cross-linked and
      covalently cross-linked aminophthalhydrazides.
AB  - Transglutaminases catalyse an acyl-transfer reaction between the gamma
      carboxamide of a protein or peptide-bound glutamine (P-CH2-gammaCH2-CO-1NH2) and
      the primary amino group of mono- or polyamines (R-2NH2), covalently cross-linking
      the reactants by an isopeptide bond: P-CH2-gammaCH2-CO-1NH2 + R-2NH2 --> P-CH2
      gammaCH2-CO-2NH-R + 1NH3. We reported that N-(4-aminobutyl)-N-ethylisoluminol
      (ABEI) was a chemiluminescent (CL) amine substrate for transglutaminases. We now
      identified N-(6-aminohexyl)-N-ethylisoluminol (AHEI) as a second, less reactive,
      transglutaminase substrate. A structure-based explanation is offered for the
      lower reactivity of AHEI. Optimum CL from non-cross-linked or cross-linked ABEI
      or AHEI was elicited in the presence of 10 mmol/L dithiothreitol, by oxidizing
      with a mixture of 20 mmol/L potassium ferricyanide and 10 mmol/L hydrogen
      peroxide in 100 mmol/L NaOH. The limits of detection and quantitation for non
      cross-linked aminophthalhydrazides obtained in this system were: 20 fmol and 60
      fmol for ABEI and 10 fmol and 30 fmol for AHEI. These values represented a 500
      800-fold improved sensitivity. Delayed peak CL and CL decay in the presence of
      dithiothreitol contributed to improving the sensitivity. The data could be useful
      for improving the immunoassays for aminophthalhydrazides and facilitate the
      development of high throughput assays for transglutaminases.

PMID- 11512141
TI  - Enhanced firefly bioluminescent assay of adenosine 5'-triphosphate using
      liposomes containing cationic cholesterols.
AB  - Cationic liposomes composed of phosphatidylcholine and cationic cholesterols were
      prepared by extrusion technique. Dimethylaminoethyl-carbamoyl cholesterol (DMAE
      chol) and diethylaminoethyl-carbamoyl cholesterol (DEAE-chol) were synthesized as
      a cationic cholesterol. Cationic liposomes containing DMAE-chol and DEAE-chol
      enhanced the intensity of maximum light emission from the firefly bioluminescent
      (BL) reaction. The sensitivity for ATP in the presence of cationic liposomes
      containing DMAE-chol and DEAE-chol was improved by a factor of 10 times compared
      to that in water alone. The detection limit for ATP upon using cationic liposomes
      was 1.0 pmol/L in an aqueous standard solution. The BL enhancement in the
      presence of cationic liposomes could be explained in terms of BL emitters and
      electrostatic interaction between the liposomes surface and BL reactants.

PMID- 11512142
TI  - Kinetic analysis of bacterial bioluminescence in water-organic media.
AB  - The interaction of luciferases from two types of luminous bacteria,
      Photobacterium leiognathi and Vibrio harveyi, with their substrates [the
      photorecovered FMNH2 and long-chain aldehydes--decanal (C10), dodecanal (C12) and
      tetradecanal (C14)] in water-organic media was analysed using kinetic graphical
      methods. Moderate concentrations of organic solvents have been demonstrated to
      activate the bioluminescence, while higher concentrations inhibit it. The
      interactions of these effectors with luciferases show different types of
      kinetics, which depend on concentrations of solvents, kinds of enzymes and
      substrates. The apparent value of the Michaelis constant, Km, for C14 of both
      luciferases and for C10 of luciferase V. harveyi is enhanced with increasing
      concentration of the organic solvent, but Km for C12 and C10 of luciferase P.
      leiognathi decreases. Obviously, at the specific binding of aldehydes with
      luciferases in the first case, hydrophobic interactions are realized, but in
      second, the electrostatic interactions are realized. The series of changes in
      parameters of bioluminescence reaction catalysed by different luciferases is
      obviously determined by their structural peculiarities.

PMID- 11512143
TI  - Design and synthesis of chemiluminescent substrates with high luminescent
      efficiency in an aqueous system: 5-tert-butyl-4,4-dimethyl-2,6,7
      trioxabicyclo[3.2.0]heptanes bearing a 3-hydroxy-4-(1-iminoethyl)phenyl moiety at
      the 1-position.
AB  - A CIEEL-active dioxetane bearing a 4-acetyl-3-hydroxyphenyl moiety has very
      recently been found to emit light effectively, even in an aqueous system, albeit
      with a very slow CIEEL decay rate. As an attempt to improve the CIEEL decay rate
      of this type of dioxetane, three dioxetanes, in which a carbonyl in the 4-acetyl
      3-hydroxyphenyl moiety was modified into an oxime, oxime O-methyl ether, or
      semicarbazone, were synthesized. These three dioxetanes decomposed to emit light
      far more rapidly than the parent 4-acetyl-3-hydroxyphenyl-substituted dioxetane.
      Among them, a dioxetane bearing a 3-hydroxy-4-(1-methoxyiminoethyl) phenyl,
      namely an oxime O-methyl ether derivative, gave high chemiluminescent efficiency.
      As for a semicarbazone derivative, decrease of the chemiluminescent yield was
      minimal, even in an aqueous system.

PMID- 11512144
TI  - Increased carbon disulfide-stimulated chemiluminescence in the pyrogallol-luminol
      system.
AB  - We studied the effect of carbon disulphide (CS2) on the generation of superoxide
      anion (O2-*) and its chemiluminescence (CL) in the pyrogallol-luminol system.
      Testing was conducted with the pyrogallol-luminol system to observe the CL
      dynamic curve of CS2 and the inhibition by superoxide dismutase (SOD) on CL
      induced by CS2. Compared with the ethanol solvent control, CS2 enhanced the
      emission intensity of CL and delayed the peak time. There was a significant dose
      concentration relationship between CS2 concentrations (10, 40, 80 mg/mL) and CL
      peak (r = 0.975 p = 0.012) and CS2 concentrations and peak time (r = 0.990, p =
      0.005). The CL peak at 80 mg/mL CS2 was higher than that in a background without
      ethanol. The enhanced CL evoked by CS2 could be inhibited by SOD. The results
      suggest that CS2 can induce the pyrogallol-luminol system to generate an
      increased amount of O2-* and delay the CL peak time.

PMID- 11512145
TI  - Development of ultra-high sensitivity bioluminescent enzyme immunoassay for
      prostate-specific antigen (PSA) using firefly luciferase.
AB  - A bioluminescent enzyme immunoassay (BLEIA) for prostate-specific antigen (PSA)
      using biotinylated firefly luciferase-labelled antibody was developed. PSA is an
      important marker for the diagnosis and management of prostate cancer. Our BLEIA
      for PSA, based on the two-step sandwich method, had ultra-high sensitivity and a
      very wide measurable range. The detection limit (mean of nine replicates of the
      zero standard +2 SD) for PSA was 0.25 pg/mL and the measurable range for PSA was
      0.25 pg/mL-100 ng/mL. Generally, PSA in the serum exists on two forms, called
      free PSA (f-PSA) and complex PSA (c-PSA), which is formed with alpha
      antichymotripsin. Thus, the response of the PSA assay to these two forms has to
      be equimolar in the construction of the assay system. Our BLEIA for PSA also had
      an equimolar response to them.

PMID- 11512146
TI  - Influence of carbon disulphide on hydroxyl radicals in the phenanthroline
      chemiluminescence system.
AB  - We investigated the effects of carbon disulphide (CS2) on hydroxyl radical
      generation using the phenanthroline chemiluminescence system. The influence of
      CS2 on the phenanthroline chemiluminescence system without CuSO4 and vitamin C
      were tested. The results showed that CS2 enhanced the emission intensity of
      chemiluminescence and advanced the peak time of the chemiluminescence. There was
      a dose-effect relationship between CS2 concentrations (0-160 mg/ml) and
      chemiluminescence peak intensity (r = 0.955, R2 = 0.913, p = 0.003), as well as
      CS2 concentrations and peak time (r = -0.927, R2 = 0.860, p = 0.008). The
      enhanced chemiluminescence induced by CS2 could be inhibited by thiourea, and the
      inhibition rate gradually deceased along with increasing CS2 concentration (r = 
      0.816, R2 = 0.666, p = 0.048). When the system was free of CuSO4 and vitamin C,
      CS2 also induced the emission of chemiluminescence intensity. We conclude from
      these results that CS2 can induce the phenanthroline chemiluminescence system to
      generate hydroxyl radicals and advance the peak time, and that thiourea can
      inhibit the effect. The mechanism may be explained by a catalytic effect of CS2
      directly on H2O2.

PMID- 11512147
TI  - A study of common interferences with the forensic luminol test for blood.
AB  - A wide range of domestic and industrial substances that might be mistaken for
      haemoglobin in the forensic luminol test for blood were examined. The substances
      studied were in the categories of vegetable or fruit pulps and juices; domestic
      and commercial oils; cleaning agents; an insecticide; and various glues, paints
      and varnishes. A significant number of substances in each category gave
      luminescence intensities that were comparable with the intensities of undiluted
      haemoglobin, when sprayed with the standard forensic solution containing aqueous
      alkaline luminol and sodium perborate. In these cases the substance could be
      easily mistaken for blood when the luminol test is used, but in the remaining
      cases the luminescence intensity was so weak that it is unlikely that a false
      positive test would be obtained. In a few cases the brightly emitting substance
      could be distinguished from blood by a small but detectable shift of the peak
      emission wavelength. The results indicated that particular care should be taken
      to avoid interferences when a crime scene is contaminated with parsnip, turnip or
      horseradish, and when surfaces coated with enamel paint are involved. To a lesser
      extent, some care should be taken when surfaces covered with terracotta or
      ceramic tiles, polyurethane varnishes or jute and sisal matting are involved.

PMID- 11512148
TI  - Mechanisms of resistance to imatinib (STI571) and prospects for combination with
      conventional chemotherapeutic agents.
AB  - Imatinib (STI571, Glivec) is a small molecule drug selected for its ability to
      inhibit the Bcr-Abl kinase, the pathogenic molecular abnormality in chronic
      myelogenous leukemia (CML). It also is an efficient inhibitor of the Kit and
      platelet-derived growth factor receptor tyrosine kinases. In vitro studies have
      demonstrated that this drug potently inhibits proliferation and induces apoptosis
      of cells that depend on activation of these kinases. Phase I clinical studies
      have demonstrated remarkable activity against CML. However, these studies, as
      well as a variety of experimental models, have suggested that clinical resistance
      to STI571 could develop. The mechanisms for the development of this resistance
      will be discussed along with the potential for circumventing STI571 resistance by
      combining it with traditional anti-neoplastic agents.

PMID- 11512149
TI  - Mechanisms of resistance imatinib (STI571) in preclinical models and in leukemia
      patients.
AB  - The tyrosine kinase inhibitor imatinib (STI571, Glivec) blocks the activity of
      the BCR/ABL oncogene and induces hematologic remissions in the majority of
      patients with chronic myeloid leukemia (CML). Glivec is an aminopyrimidine
      derivative that interacts with the ATP-binding site within the kinase domain of
      ABL and several other tyrosine kinases, including c-KIT, PDGF beta receptor, and
      ARG. The compound is currently in phase III clinical trials. Although patients
      with chronic phase CML have been found to develop drug resistance only rarely so
      far, patients in more advanced phases of the leukemia develop resistance
      frequently. The available information on Glivec resistance will be reviewed.

PMID- 11512150
TI  - Mother-to-child transmission of drug-resistant HIV.
AB  - Mother-to-child transmission of HIV-I is responsible for the infection of
      hundreds of thousands of infants every year. The use of prophylactic
      antiretroviral treatments has brought about a dramatic decrease in the risk of
      transmission. Nevertheless, vertical transmission can still occur. In some cases,
      the presence of drug-resistant HIV-I strains in the mother has been responsible
      for the failure of the prophylactic scheme. Moreover, these strains have also
      been detected in the newborn. The aim of this review is to provide updated
      information on mother-to-child transmission of drug-resistant HIV strains and to
      help guide treatment decisions during pregnancy.

PMID- 11512151
TI  - Factors determining cellular mechanisms of resistance to antimitotic drugs.
AB  - With the rapidly expanding use of paclitaxel and related taxanes to treat
      malignant diseases, comes the realization that development of resistance to this
      class of agents will become an increasingly significant clinical problem. Studies
      have indicated that acquisition of resistance to the cytotoxic action of these
      drugs can occur by limiting the drug's ability to accumulate in cells, altering
      the stability of cellular microtubules, diminishing the drug's ability to bind
      tubulin, or varying the expression of specific tubulin genes. This review will
      critically evaluate the selection methods used to generate drug resistant mutants
      in tissue culture and focus on the various factors that determine which
      resistance mechanisms are most likely to be encountered. It is anticipated that
      clinical drug resistance will be complicated by pharmacokinetic considerations
      and variability among individuals, but that underlying genetic mechanisms will be
      similar to those found in culture.

PMID- 11512152
TI  - Membrane and cell wall targets in Aspergillus fumigatus.
AB  - Antifungal drugs directed against the human opportunistic fungal pathogen
      Aspergillus fumigatus are limited in number and ergosterol-targeted: the polyenes
      bind to the membrane ergosterol and the azoles block the ergosterol biosynthesis
      pathway. The efficacy of the drugs currently available for clinical use
      (amphotericin B and itraconazole) is limited and the frequent occurrence of
      therapeutic failures in the treatment of invasive aspergillosis emphasizes the
      need for the development of new agents. Cell wall biosynthetic pathways have been
      recognized for a long time as essential and unique specific drug targets. Recent
      studies of the chemical organization of the cell wall of A. fumigatus together
      with comparative analysis of yeast cell wall data have shown that beta 1-3 glucan
      branching and chitin-beta 1-3 glucan binding are essential exocellular enzymatic
      steps in cell wall biosynthesis. The enzymes involved in the biosynthesis and
      remodeling of cell wall polysaccharides especially in A. fumigatus are reviewed.

PMID- 11512153
TI  - Glycolysis as a target for the design of new anti-trypanosome drugs.
AB  - Glycolysis is perceived as a promising target for new drugs against parasitic
      trypanosomatid protozoa because this pathway plays an essential role in their ATP
      supply. Trypanosomatid glycolysis is unique in that it is compartmentalized, and
      many of its enzymes display unique structural and kinetic features. Structure-
      and catalytic mechanism-based approaches are applied to design compounds that
      inhibit the glycolytic enzymes of the parasites without affecting the
      corresponding proteins of the human host. For some trypanosomatid enzymes, potent
      and selective inhibitors have already been developed that affect only the growth
      of cultured trypanosomatids, and not mammalian cells.

PMID- 11512154
TI  - The ABC transporter genes of Plasmodium falciparum and drug resistance.
AB  - The seminal observations that (a) chloroquine-resistant Plasmodium falciparum
      strains accumulate less drug than more sensitive parasites, and (b) chloroquine
      resistance could be modulated in vitro by the classic multidrug-resistance (MDR)
      modulator verapamil, suggested not only that parasite resistance to multiple
      drugs may be similar to the MDR phenotype described in mammalian cancer cells,
      but that homologous proteins may be involved. These findings prompted search for
      MDR-like genes in the parasite. To date, three full-length ABC transporter genes
      have been isolated from P. falciparum: two P-glycoprotein-like homologues, pfmdr1
      and pfmdr2, and a homologue of the yeast GCN20 gene, pfgcn20.

PMID- 11512155
TI  - Targeting tumor cell resistance to apoptosis induction with antisense
      oligonucleotides: progress and therapeutic potential.
AB  - Despite the use of combination chemotherapy and immunotherapy, the survival rate
      of adult cancer patients has only moderately increased. Diminished apoptosis, due
      to overexpression of anti-apoptotic proteins, is involved in tumorigenesis and
      treatment resistance. Antisense oligonucleotides can be used to specifically
      inhibit unwanted gene expression and hence target the molecular basis of genetic
      diseases. Recently developed antisense oligonucleotides with the ability to
      inhibit the expression of anti-apoptotic proteins, including Bcl-2, Bcl-xL, FLIP
      and surviving, have been shown to facilitate tumor cell apoptosis and sensitize
      tumor cells to cytotoxic treatments. This suggests their use in combination with
      conventional treatments as an approach to more effective cancer therapy.

PMID- 11512156
TI  - Use of a computer software program for qualitative analyses--Part 1: Introduction
      to NUD.IST.
AB  - The NUD.IST (Non-numerical Unstructured Data Indexing, Searching, and Theorizing)
      program is recognized as one of the most efficient software programs for
      qualitative data analysis because it dramatically reduces the clerical tasks of
      cut and paste for coding and retrieval in text. However, little literature
      related to NUD.IST and its use in qualitative analysis is available to nurse
      researchers. Thus, the purposes of the first part of a two-part article are to
      describe the features of NUD.IST to nurse researchers and to present how NUD.IST
      was used in a qualitative study of dyspnea stimuli. In managing the qualitative
      data of dyspnea stimuli, NUD.IST 3.0 was effective in extracting, retrieving, and
      tracking text segments as well as identifying commonalties or patterns in data
      quickly.

PMID- 11512157
TI  - Are egalitarian relationships a desirable ideal in nursing?
AB  - Recent discourse in nursing's various theoretical enterprises has been dominated
      by a passionate concern for the moral principle of equality. Although
      philosophical claims about equality shape current thinking in nursing education,
      research, and practice theory, this author contends that the dialogue has
      eclipsed an egalitarian view of justice and created the conditions under which
      only narrow, individualistic, and prima facie interpretations of equality can be
      sustained. Current interpretations of equality are linked to systematic patterns
      in theoretical reasoning and its application to various nursing contexts. Many
      nurse theorists have uncritically adopted equality as an incontestable and
      overarching truth, such that its limitations are overlooked and competing
      positions not afforded serious consideration; extreme and dichotomous positions
      proliferate within nursing scholarship. Deconstruction of the dominant discourse
      around equality raises questions about the way justice and truth are understood
      within nursing's theoretical, educational, and research scholarship.

PMID- 11512158
TI  - Can justice coexist with the supremacy of personal values in nursing practice?
AB  - This article explores a relationship between justice and personal values,
      typically understood as illustrative of universalist and particularist accounts
      of morality, and therefore, as oppositional. The possibility of the coexistence
      of personal values and justice depends on the conceptualization of justice and
      the nature of the personal values. In contrast to traditional conceptions, the
      author presents an alternative and feminist view of justice in which the
      universalist and particularist accounts of morality need not conflict. The author
      argues that personal values that work in such a way so as to include previously
      marginalized others in the group of those who have access to the goods of social
      life are the personal values that are compatible with justice. In conclusion, the
      author focuses on the implications for the care/justice debate, the necessity of
      political participation, and the importance of educating for justice.

PMID- 11512159
TI  - What constitutes a nursing practical skill?
AB  - Practical nursing skills ensure patients' physical comfort, hygiene, and safe
      medical treatment. The learning, performance, or significance of nursing
      practical skills are seldom a theme in theoretical and philosophical debate or
      the topic of research within nursing. This might be due to a long-standing
      behavioristic tradition in nursing of viewing nursing practical skills in a
      simplistic way, only as correctly sequenced motor movement. The purpose of this
      article is to bring forth an argument for a broader understanding of the
      constitution of nursing practical skills. This argument is substantiated by a
      review of past and present conceptualizations of nursing practical skills as well
      as by philosophical reflections on the value of practical skills in the nursing
      profession. Nursing practical skills embrace dimensions of performance,
      intention, and nursing "disciplined" understanding.

PMID- 11512160
TI  - A matter of extinction or distinction.
AB  - In view of fiscal constraints and the increasingly technical environments of
      health care, the essential and unique contributions of all health care providers,
      including nurses, are being challenged. This article examines current challenges
      to the role of nurses and the future of nursing as a unique discipline. As the
      work of nurses becomes increasingly defined by the technologies of care, what
      will distinguish nursing from other disciplines and nurses from other care
      providers? Can nurses lay claim to uniqueness in their knowledge base, technical
      competencies, and caring behaviors? Other types of workers are increasingly
      rendering elements of clinical care traditionally provided by nurses. As we move
      into the next millennium, will nursing become extinct or distinct as a health
      care profession?

PMID- 11512161
TI  - Is practical nursing experience necessary in administration, education, and
      research?
AB  - Because nursing is a practice discipline involving a relationship between nurse
      and client based on moral commitments of nurse to client, it is critically
      important that nurse administrators, educators, and researchers have experienced
      that relationship in practice. Nurse administrators need that basis to found a
      vision of nursing required to lead and guide. Nurse educators need to have
      experienced nursing practice to engage nursing students in praxis, that act of
      reflection and action. Nurse researchers need to have practiced nursing to
      identify critical areas of focus in nursing practice and to give meaning to the
      interpretation of findings. The author urges greater convergence and clarity in
      identifying the nonnegotiables of nursing's art and science, including the
      importance of nursing practice as foundational to nursing work.

PMID- 11512162
TI  - Answering philosophical questions facing contemporary nursing practice.
AB  - The purpose of the article is to point out the relevance of asking and answering
      philosophical questions in nursing. The author characterizes philosophical
      questions as higher order questions that cannot be answered by empirical
      observations alone. Questions about the nature of nursing reality, about the
      nature of nursing knowledge, and about the validity of ethical principles are
      mentioned as examples of such questions. The means for dealing with philosophical
      questions in nursing range from formal, logical analysis to philosophical poems.

PMID- 11512163
TI  - Is integrative science necessary to improve nursing practice?
AB  - This article explores integrative science as a perspective for overcoming
      intellectual barriers between nurses' valuing of the holistic person and the
      science and technology that drives advances in health care. Several meanings of
      integrative science are reflected in health science literature. One use of
      integrative science refers to comprehensive and unifying theories (or viewpoints)
      that draw together interrelated aspects of a field. Another use of integrative
      science pertains to efforts to formulate models that accommodate the special
      dualities that exist in studying humans. Integrative science as a perspective
      addresses overcoming intellectual separation of knowledge relevant to
      understanding of persons or populations by an open-ended sharing and juxtaposing
      of knowledge relevant to solving that problem. For nursing, integrative science
      may pose a threat to nursing knowledge. Failure to thrive, a nutritional and
      psychosocial phenomenon, is presented as an example of a topic manifesting the
      need for an integrative science perspective.

PMID- 11512164
TI  - The ecstasy and the agony of family caregiving.

PMID- 11512165
TI  - Respite--a coping strategy for family caregivers.
AB  - The caregiver respite experience is seen as one way to moderate the negative
      consequences of caregiving. From an interpretivist research orientation, this
      study explored how 10 family caregivers of persons with dementia experienced
      respite. From a coping theoretical perspective, the caregiver respite experience
      is discussed as a process of "getting out" of the caregiver world, and is linked
      to avoidance strategies of emotion-focused coping. The following three phases
      within the coping dimension of the respite experience were found: caregivers
      recognizing their need to get out of the caregiver world, giving themselves
      permission to actually get out from it temporarily, and having the appropriate
      social support resources available to facilitate the getting out. The critical
      practice and research implications linked to caregivers' ability to acknowledge
      their need for respite are described.

PMID- 11512166
TI  - Is there a difference between family caregiving of institutionalized elders with
      or without dementia?
AB  - Based on the stress and coping model of Lazarus and Folkman, the aim of this
      comparative study was to determine whether the caregiving experience of the
      caregivers of an institutionalized demented relative is different from the one of
      the caregivers whose relative does not suffer from dementia. Five dimensions of
      the caregiving experience were considered: stressors, cognitive appraisal of the
      stressors, social support, coping strategies and well-being. The sample consisted
      of primary caregivers of a demented and a nondemented relative. Results revealed
      that the caregivers of a demented relative were exposed to more stressors than
      the caregivers of a nondemented relative. Functional impairment as well as
      depressive behaviors were appraised as more disturbing. According to MANCOVA
      analysis, formal and informal social support seems to play a protective role in
      the psychological distress of the caregivers of a demented relative. There was no
      difference between the two groups with regard to their coping strategies.
      Overall, the caregivers of a demented relative seemed to experience some
      dimensions of caregiving in a different way compared with their counterparts, and
      the nature of dementia in itself helps to explain this difference.

PMID- 11512167
TI  - Fatigue among elders in caregiving and noncaregiving roles.
AB  - Fatigue is a complex symptom prevalent in informal caregiving. When role demands
      exceed caregiver resources, fatigue ensues and caregiving can be compromised. The
      purpose of this study was to compare perceptions of fatigue among older adults (N
      = 92) caring for spouses with Alzheimer's disease, Parkinson's disease, or cancer
      with a control group of older adults (N = 33) whose spouses required no extra
      care. Caregiving elders reported more fatigue, less energy, and more sleep
      difficulty than did control participants. All caregiving groups reported similar
      levels of fatigue, energy, sleep, and self-reported health even though there were
      marked differences regarding spousal status. Health care providers can support
      older caregivers in monitoring their own health and in recognizing the need for
      services that support the caregiving role.

PMID- 11512168
TI  - Grief in spouse and children caregivers of dementia patients.
AB  - Caring for a family member with dementia involves loss and inevitable grief
      during the illness duration. The purpose of this study was to determine the
      patterns of grief of caregivers of family members with dementia and the
      relationship of those patterns to the losses and experiences of the caregivers.
      Participants were 22 spouse caregivers and 11 adult children caregivers of family
      members with dementia. Caregivers' experiences were measured using visual analog
      scales and grief using The Grief Experience Inventory. Caregivers' perceptions of
      the level of affection before the illness and the satisfaction of the marriage
      before the illness were inversely related to grief symptoms. Grief symptoms were
      also related to participants' perceptions of loss of the future. Caregivers'
      emotional distress includes reaction to the losses they are encountering long
      before their care recipients die.

PMID- 11512169
TI  - Self-reported health-promoting behaviors of black and white caregivers.
AB  - The purpose of this study was to describe the behaviors that caregivers report
      carrying out to maintain their own health, and to compare the health-promoting
      behaviors of Black and White caregivers. Although many studies have examined
      health-promoting behaviors, few have examined health promotion among caregivers.
      Reported studies of caregivers' health-promoting behaviors have not compared
      cultural groups. The sample for this study was selected by random digit dialing,
      and included 136 Black and 257 White caregivers of frail elders. Content analysis
      of respondents' answers to the open-ended question, "In general, what do you do
      to stay healthy?" was used to address the research questions. Most caregivers
      reported specific behaviors they engaged in for the purpose of staying healthy.
      Although most of their behaviors addressed physical health, caregivers also
      mentioned behaviors that contribute to mental and spiritual health. Both
      differences and similarities were found in Black and White caregivers' self
      reported health behaviors, which have important implications for nursing practice
      and research in the future.

PMID- 11512170
TI  - Family involvement in the nursing home.
AB  - The focus of this study was the influence of preestablished family behavior
      patterns, family orientation of nursing home policies, and practices and
      caregiver and elder characteristics on the family members' expectations for
      involvement in the nursing home and the actual involvement 6 months later. The
      conceptual model was based on findings of Montgomery's nursing home study and
      open systems principles applicable to families. Data were collected through
      telephone interviews with 216 family members of residents in 24 nursing homes in
      southern Michigan. Regression analyses revealed that measures of preestablished
      patterns of family behavior accounted for 19% to 31% of variance in measures of
      expected family involvement. Expected family involvement, resident activities of
      daily learning (ADL), and caregiver relationship accounted for 11% to 23% of
      variance in measures of actual family involvement. Opportunity for family
      leadership in resident care had a mild effect of moderating the amount of family
      direct care and learning activities in the nursing home.

PMID- 11512171
TI  - Male caregivers' use of formal support.
AB  - The purpose of this study was to explore male caregivers' perceptions of formal
      support. The men were caregivers of adults with cognitive impairment. The study
      involved secondary analysis of interview data on perceptions of support that had
      not been previously analyzed from the perspective of formal support. Techniques
      of data analysis used in grounded theory were applied to 62 guided interactive
      interviews conducted with 24 male caregivers during a period of 18 months. The
      men experienced a process of making concessions for care in the following four
      sequential stages: resisting, giving in, opening the door, and making the match.
      Personal barriers deterred the caregivers from seeking help, and once the
      caregivers engaged formal help the influence of characteristics of the health
      care system and individual staff members had both enabling and disabling effects.
      For caregivers whose use of formal support involved admitting their relative to a
      long-term care facility, the phase of making the match was followed by
      redesigning their caregiver role.

PMID- 11512172
TI  - Conceptual and technical considerations when combining large data sets.
AB  - Secondary analysis provides a useful method for the development of new knowledge.
      Larger samples can be constructed, and secondary analysis can be enhanced when
      data sets are combined. A standardized method for combining large data sets is
      crucial, yet literature on methods for combining large data sets for secondary
      analysis is lacking. The purpose of this article is to outline and explain the
      process of combining two or more large data sets (n = 276, n = 125) for secondary
      analysis by using these authors' previous work with large oncology and AIDS
      caregiver data sets.

PMID- 11512173
TI  - Issues to consider when choosing and using large national databases for research
      of families.
AB  - Secondary analysis of large national databases offers promise for research of
      families. In this article, issues that the secondary analyst must consider when
      choosing a database for research of families are described. Potential advantages
      and limitations of databases are discussed. Strategies to minimize potential
      limitations are highlighted.

PMID- 11512174
TI  - Conceptual and pragmatic considerations in conducting a secondary analysis. An
      example from research of families.
AB  - In this article, the authors discuss conceptual and pragmatic considerations for
      conducting research of families using large secondary data sets. Conceptual
      considerations include establishing consistency among the theory, variables, and
      available data, and determining reliability and validity of the data in the
      context of the theory. Pragmatic considerations include the use of resources such
      as management of the data among several authors, criteria and methods for
      selection of a subsample, and, recoding of the data to examine dyadic difference
      scores. The Family Special Interest Group of the Eastern Nursing Research Society
      initiated this research as part of a project to analyze families using large
      national data sets. The purpose of the secondary analysis was to identify family
      beliefs about healt-promoting behaviors. Combining parent and teen data to create
      relational level data resulted in new information that had not been identified in
      the original survey.

PMID- 11512176
TI  - Stress, social support, and sense of coherence.
AB  - In the Salutogenic Model, Aaron Antonovsky suggested that a sense of coherence
      (SOC) is the key determinant in the maintenance of health. He theorized that
      individuals with a strong SOC have the ability to (a) define life events as less
      stressful (comprehensibility), (b) mobilize resources to deal with encountered
      stressors (manageability), and (c) possess the motivation, desire, and commitment
      to cope (meaningfulness). To determine the effects of SOC on health outcomes, a
      greater understanding of the development and maintenance of SOC is necessary.
      Data from the 1994 Canadian National Population Health Survey were analyzed to
      investigate the effects of stress, social support, and recent traumatic life
      events on SOC. As predicted, stress and recent traumatic events were found to be
      inversely related to SOC, and social support was positively related. Traumatic
      events encountered in childhood were stronger predictors of SOC than traumatic
      life events experienced in adulthood.

PMID- 11512175
TI  - Parent-teen worry about the teen contracting AIDS.
AB  - A secondary data analysis of the National Commission on Children: 1990 Survey of
      Parents and Children was conducted with a subsample of 457 parent-teen pairs who
      responded to the "worry about AIDS" question. The teen's worry about contracting
      AIDS was associated with race, parent's education, the amount of discipline from
      the parent for engaging in sex, the teen's desire to talk to the parent about the
      problem of sex, the teen's rating of the neighborhood as a safe place to grow up,
      whether the parent listened to the teen's telephone interview, and the parent's
      response to whether his or her teen had a history of sexually transmitted
      disease. Of the parent-teen pairs in the subsample, 46% (N = 210) agreed in their
      responses about worry. Agreement was more frequent among the parent-teen pairs
      when compared to randomly constructed surrogate pairs. Dyadic analysis supported
      a family system view of perceived susceptibility.

PMID- 11512177
TI  - Organ and tissue weight presentation in rat populations.
AB  - Multiple ways of reporting organ weights are sources of confusion in literature.
      This study was designed to determine if there is a linear relationship between
      body weights and selected organ and tissue weights in groups of rats after
      different liquid feeding options. A randomized 2 x 2 x 2 factorial, randomized
      block design was used with 40 postpubescent male rats with two levels of feeding
      schedules, kilocalorie levels, and fiber contents. In addition to a skeletal
      muscle, 13 abdominal and thoracic organs or tissues were weighed. Pearson product
      moment correlation coefficients and regression analyses were completed to
      determine the relationship between these weights and the final body weights.
      Findings support the need to use different approaches in order to accurately
      report various organ and tissue weights.

PMID- 11512178
TI  - Depressive symptomatology in three Latino groups.
AB  - The purpose of this study was to examine depressive symptomatology in three
      Latino groups: Mexicans living in Mexico City, Latino immigrants living in the
      South Bay area of San Francisco, and Puerto Ricans living on the island of Puerto
      Rico. The Spanish version of the Center for Epidemiological Studies Depression
      Scale (CES-D) was used as part of a larger study on stress and coping. The levels
      of depressive symptomatology in all three Latino groups were significantly higher
      than those reported in other Latino samples and in White Americans. Mexican
      immigrants reported the highest levels of depressive symptomatology.

PMID- 11512179
TI  - Discovering a dialectic of care.
AB  - Using data from a recent study on the outcomes of child psychiatric
      hospitalization, the author presents a critique of the intervention-outcome
      movement that dominates the health care agenda. Employing an exploratory
      descriptive study design and Denzin's interpretive interactionism method, she
      presents data that illustrate how interventions can become distorted by
      contextual factors, conflicting ideologies, agendas, and failure to thoughtfully
      consider patient needs. She posits that research agendas are heavily tilted
      toward outcomes research that often discount the nature of structure and process.
      The marketplace emphasis of health care may result in environments in which a
      structure and process of caring is replaced by a focus of profits over patients.
      The value of focusing on interventions and outcomes in research without
      addressing broader ecosystem variables that influence practice is questioned in
      view of in-depth data that emerge from practice settings.

PMID- 11512180
TI  - Nurses' participation in the euthanasia programs of Nazi Germany.
AB  - During the Nazi era, so-called euthanasia programs were established for
      handicapped and mentally ill children and adults. Organized killings of an
      estimated 70,000 German citizens took place at killing centers and in psychiatric
      institutions. Nurses were active participants; they intentionally killed more
      than 10,000 people in these involuntary euthanasia programs. After the war was
      over, most of the nurses were never punished for these crimes against humanity-
      although some nurses were tried along with the physicians they assisted. One such
      trial was of 14 nurses and was held in Munich in 1965. Although some of these
      nurses reported that they struggled with a guilty conscience, others did not see
      anything wrong with their actions, and they believed that they were releasing
      these patients from their suffering.

PMID- 11512181
TI  - Random assignment and patient choice in a study of alternative pain relief for
      sickle cell disease.
AB  - This article presents two case examples in which women with sickle cell disease,
      when invited to participate in a nursing experiment, requested assignment to the
      experimental group. This experience stimulated the authors to explore the ethics
      of random assignment relative to equipoise, informed consent, patient choices,
      study validity, the clinician-patient relationship, patient support networks, and
      other issues. There is a need for in-depth discussion about random assignment and
      its implications within the nursing research and advanced practice communities.

PMID- 11512182
TI  - Hopefulness and its characteristics in adolescents with cancer.
AB  - Hopefulness in adolescents with cancer serves critical functions related to the
      adolescents' sense of well-being and commitment to treatment. Given these
      critical functions, it is important to determine the essential characteristics of
      hopefulness, which include the degree and dynamism of hopefulness and the nature
      and attributes of hoped-for objects. The purposes of this two-site study were to
      describe the degree and dynamism of hopefulness at four time points during the
      first 6 months of adolescents' treatment for newly diagnosed cancer, to identify
      and describe the adolescents' hoped-for objects, and to evaluate potential
      relationships between the characteristics of hopefulness and patient gender, age,
      diagnosis, and time point in treatment. Seventy-eight adolescents completed the
      Hopefulness Scale for Adolescents, the Hopelessness Scale, and the Hopefulness
      Interview Question at each time point. Hopefulness scores were higher and
      hopelessness scores substantially lower than reported in other tested samples.
      Adolescents identified a total of 57 different hopes. Differences by age, gender,
      and diagnosis were found.

PMID- 11512183
TI  - An adolescent and young adult condom perception scale.
AB  - A methodological study was conducted to initially test the psychometric
      properties of an adolescent and young adult condom perception scale. A 25-item
      scale measured the constructs of perceived benefits and barriers to using condoms
      in preventing human immunodeficiency virus and other sexually transmitted
      diseases. The items were developed based on a review of the literature and a
      review by experts who work with adolescents. The scale was self-administered to
      209 voluntary participants (13 to 26 years of age), with 198 completing without
      missing data. Item analysis (interitem correlations, item to total correlations,
      and contribution to alpha coefficient) was conducted, and 10 items were deleted.
      Principal axis factor analysis with varimax rotation yielded three factors, which
      accounted for 44% of the variance. The factors were relationship-oriented
      barriers, condom benefits, and sexual satisfaction barriers. The total scale had
      an alpha coefficient of .82. The scale should be beneficial to further research
      of condom perceptions and use.

PMID- 11512184
TI  - Cross-cultural study of beliefs about smoking among teenaged females.
AB  - This study was designed to identify beliefs associated with smoking behavior in
      three different ethnic groups of teenaged females. The Neuman Systems Model
      provided the conceptual framework, and the Theory of Planned Behavior provided
      the basis for the development of the research instrument. Participants included
      141 African American, 146 Puerto Rican, and 143 non-Hispanic White females, ages
      13 to 19. Logistic regression analyses identified beliefs that were significantly
      related to smoking behavior in each ethnic group. Beliefs related to attitudes
      about smoking and perceived social pressure regarding smoking differed among the
      three ethnic groups. The findings suggest that specific beliefs distinguish
      between smokers and nonsmokers and that some beliefs differ by ethnicity.

PMID- 11512185
TI  - Perceptions about substance use among male adolescents in juvenile detention.
AB  - Although adolescents in juvenile detention represent a vulnerable population who
      are exposed to situations that foster risk-taking behaviors, few studies have
      been conducted with detained adolescents to determine their perceptions regarding
      substance use. Ethnographic interviews and observations were conducted with 20
      male adolescents who resided in a large metropolitan area juvenile detention
      facility, to discover their substance use beliefs and the decisions they make to
      continue or discontinue substance use or abuse. The participants described how
      they initiated substance use and said that they had rarely made active decisions
      about substance use until they were detained. They explained the decisions they
      made, while they were in detention, to stop or cut down their substance use after
      release. They talked about the problems they anticipated when they returned home
      and how they hoped to balance their resolutions with their reputations and
      obligations. Time-out in juvenile detention may offer nurses the opportunity to
      capitalize on the potential readiness of detained adolescents to make resolution
      decisions regarding risky behaviors. Findings from a similar study conducted with
      20 detained adolescent women were reported elsewhere.

PMID- 11512186
TI  - Effects of traumatic events, social support, and self-efficacy on adolescents'
      self-health assessments.
AB  - The purpose of this study was to examine the relationship between adolescents'
      exposure to traumatic events and their self-health assessments, and to examine
      the protective effects of social support and self-efficacy on this relationship.
      Survey results (N = 1,427) indicated that experiencing violent and nonviolent
      negative life events and being exposed to a disaster were inversely associated
      with adolescents' positive health assessments. As social support and self
      efficacy decreased, adolescents' health assessments worsened. Female and Black
      adolescents had less favorable health assessments than their male and White
      counterparts. Findings suggest that traumatic events are predictive of
      adolescents' health assessments and that social support and self-efficacy prevent
      adolescents' health assessments from declining following traumatic events.

PMID- 11512187
TI  - The moderator-mediator role of social support in early adolescents.
AB  - The purpose of this study was to examine social support as both a mediator and a
      moderator of the relationship between perceived stress and symptom patterns in
      early adolescents. Data were collected from 148 early adolescent boys and girls,
      ages 12 to 14, who responded to the Perceived Stress Scale, the Personal Resource
      Questionnaire 85-Part II, and the Symptom Pattern Scale. Using multiple
      regression analysis procedures specified for the testing of moderation and
      mediation, results indicated that social support did not play a moderating role
      in the relationship between perceived stress and symptom patterns, but social
      support did play a mediating role in this relationship. The findings are
      interpreted within the two major theoretical orientations that guided the study.

PMID- 11512188
TI  - Life histories of rural Mexican American adolescents experiencing abuse.
AB  - Histories of family violence are predictors of adolescent acceptance of
      interpersonal violence within intimate relationships. This study focused on the
      progression of abusive relationships from childhood to courtship and intimacy
      among 40 rural Mexican American adolescents in the southwestern United States.
      Emphasis was on interactions that were extensions of cultural expectations for
      intimacy, family, and sex roles. Within these life histories, transgenerational
      patterns of violence were found in patterns of learning, loving and belonging
      through past and present relationships. Sex-role identification with abusive
      behavior occurred across generations, emulating roles from the past and
      perpetuating expectations for abuse as part of intimacy. Previous abusive
      experiences were described as motivation for behavioral change, yet, within the
      patterns of learning, loving, and belonging in relationships, patterns of abuse
      and behaviors similar to the family of origin were found. An understanding of the
      influential role attitudes and expectations of abused individuals and their
      families has on behavior is relevant for interventions preventing existent and
      future abuse.

PMID- 11512189
TI  - [Platelet aggregation inhibitors in diabetes mellitus].
AB  - Major cardiovascular complications and ischemic events occur more frequently in
      diabetic than nondiabetic patients. Platelets of diabetic patients are found in a
      permanent prethrombotic state. Platelet activation and aggregation with resultant
      arterial thrombus formation, are the central mechanisms in the pathophysiology of
      acute coronary syndromes. Over the past two decades aspirin was the leading
      antithrombotic agent for reduction of thrombotic events and efficacy was proven
      in many studies. The main study concerning the aspirin question was the
      "Antiplatelet Trialist's Collaboration-Study", where a successful risk reduction
      for vascular events of 25%-34% was observed with daily dosis between 75 and 325
      mg. In the last years some new, very effective drugs have been developed.
      Clopidogrel, a thienopyridine was studied in the CAPRIE trial and compared with
      aspirin. A small advantage could be proved for clopidogrel. The development of
      inhibitors of fibrinogen, binding to the platelet glykoprotein IIb/IIIa receptor
      has expanded the therapeutic spectrum for the treatment of thrombotic disorders.
      Especially in diabetic patients a significant benefit of these new drugs was
      demonstrated in various clinical indications. The newest results show the clear
      advantage of combining thrombolytic agents with the glycoprotein IIb/IIIa
      receptor antagonists in reperfusion after myocardial infarction. In conclusion
      the main message is, that diabetic patients do need antithrombotic therapy
      earlier than nondiabetic patients, that efficient drugs are available and that a
      primary prevention should be considered in this special patient group.

PMID- 11512190
TI  - [Genetic-epidemiological studies of apolipoprotein(a) polymorphism and its
      significance in nephrological diseases and type I diabetes mellitus].
AB  - Lipoprotein(a) is a highly atherogenic particle. The plasma concentrations of
      this lipoprotein are strongly related to a genetically determined size
      polymorphism of apolipoprotein(a). This article reviews some pathogenetic
      characteristics of the apolipoprotein(a) polymorphism besides its known effect on
      the lipoprotein(a) plasma concentrations. Those are the relation of the
      apolipoprotein(a) phenotype with atherogenesis, the apolipoprotein(a) phenotype
      specific elevation of lipoprotein(a) in hemodialysis patients and the advantages
      of this polymorphism for the atherosclerosis risk evaluation in high-risk
      patients. It furthermore discusses the observed association between the low
      molecular weight apolipoprotein(a) phenotype and Type I diabetes mellitus.

PMID- 11512191
TI  - Endothelial dysfunction, atherosclerosis and diabetes.
AB  - The prevalence of early and accelerated development of atherosclerosis associated
      with high morbidity and mortality is markedly increased among individuals with
      diabetes and hypertension. Although the link between diabetes and vascular
      disease is not fully understood, loss of the modulatory role of the endothelium
      could be implicated in the pathogenesis of diabetic vascular complications.
      Diabetes-associated pathophysiologic conditions in the endothelium are
      modifications of lipoproteins, formation of advanced glycation end-products and
      circulating lipoprotein immune complexes, alteration of the nitric oxide pathway,
      and elevated levels of homocysteine. The main goals in restoration of endothelial
      function are optimal glycemic control, lipid lowering, cessation of smoking,
      normalization of elevated blood pressure, improvement of the NO-status,
      antioxidants for scavenging free oxygen radicals, normalization of homocysteine
      levels, antagonizing the hyperinsulinaemia, and regulation of rheology,
      respectively haemostasis to physiological levels. There is abundant evidence that
      some pharmacological agents exert direct beneficial effects on endothelium,
      suggesting that at least part of their therapeutic action is associated with
      improvement in endothelial dysfunction. A number of new findings about
      endothelial dysfunction may have potential clinical relevance.

PMID- 11512192
TI  - [CAPD (continuous ambulatory peritoneal dialysis) in diabetic nephropathy:
      overview and general practice in the Lainz Hospital since 1982].
AB  - While there is progress in management of newly-diagnosed diabetic patients,
      treatment of diabetes and prevention of comorbid conditions, nephrologists are
      progressively confronted with the picture of fully established micro- and
      macrovascular disease. Experience with CAPD in patients with diabetes mellitus in
      the hospital Vienna-Lainz from 1982 to 8/1999 was analyzed and outcome data are
      presented. During this period 139 patients were treated with CAPD as primary
      renal replacement therapy, 41 with diabetes Type 1 and 47 with diabetes Type 2.
      Survival rate after 10 years of treatment (including transplantation and change
      to hemodialysis due to technical failure of CAPD) was 50% in type 1 diabetes and
      8% in type 2 diabetes. In 73% of patients with type 1 diabetes a kidney or kidney
      pancreas transplantation was performed. In contrast, only 11% of type 2 diabetic
      patients were eligible for kidney transplantation. These long-term data implicate
      further attempts in reducing the incidence of diabetic nephropathy and later on
      renal failure. Furthermore, screening and aggressive treatment for
      atherosclerotic complications are necessary to improve the prognosis in this
      patient cohort.

PMID- 11512193
TI  - [Evaluation of the effect of professional dental cleaning and education in dental
      hygiene in type 1 diabetic patients].
AB  - In the setting of a prospective, randomized trial the impact of professional oral
      hygiene and of intensive patient education in oral hygiene was investigated. It
      was studied, whether in young to middle-aged type 1 diabetic patients the risk or
      the progression of periodontal disease can be influenced during one year. Primary
      endpoint was bleeding at probing, secondary indices, the plaque index and probing
      pocket depth. 83 patients were enrolled, 70 completed the study according to the
      protocol. Oral cleansing was dramatically improved by education in the short
      term, however, the effect was much weaker after 6 and 12 months, respectively,
      although there remained some improvement compared to the basic level. Bleeding at
      probing increased in both groups, without reaching the level of statistical
      significance. Probing pocket depth increased in the intervention group weakly but
      significantly and remained unchanged in the control group. The tested
      intervention (professional oral hygiene, patient education in oral hygiene) could
      not improve the periodontal status in our type 1 patients.

PMID- 11512194
TI  - [Intensified smoking cessation for diabetic patients--preliminary results].
AB  - Cigarette smoking is the most prominent yet avoidable cause of illness in the
      general population as well as in patients with diabetes. The danger of developing
      late complications is much higher for smoking than for non-smoking diabetic
      patients. The aim of this study was to determine whether an intensified smoking
      cessation program for patients with diabetes, including an initial 3 week-period
      of inpatient cessation, is effective and more successful than a mere outpatient
      program. The outpatient program consisted of at least 7 consultations within 2
      years, and included nicotine replacement therapy, steps for modifying the
      smokers' behavioural patterns, advice in dietary and exercise as well as
      measurements of amounts of exhaled carbonmonoxide and lung function. In the
      inpatient program the patients passed the first 3 cessation weeks in a
      specialised clinic providing a similar, but intensified program, aside from daily
      life and professional routine. The following consultations corresponded to those
      of the outpatient program. Altogether we analysed 89 patients (64 in the
      outpatient and 25 in the inpatient program).

PMID- 11512195
TI  - [Effect of nutrition on microalbuminuria in patients with type 1 diabetes:
      prospective data evaluation over 5 years].
AB  - The possible influence of dietary components on the progression or regression of
      microalbuminuria (MA) in type 1 diabetic patients was investigated prospectively
      over 5 years. The dietary intake of 47 patients with type 1 diabetes and MA (20
      200 micrograms/min.), well instructed in diabetes management was observed in
      bimonthly intervals. Accuracy of 4-day diet protocols was verified by comparing
      the amount of documented protein intake with the measured nitrogen excretion. Non
      compliance was defined as deviation more than 30% between both values. These
      patients were eliminated from the study. Data from 37 patients with good
      compliance over a 5 year period have been used for multiple stepwise regression
      analysis. Taking into consideration Body mass index (BMI), blood pressure, HbA1c
      and time, MA was used as dependent variable, 16 dietary variables with a
      bivariate significance p < 0.05 as independent variables. The regression analysis
      (R2 = 0.589, p = 0.0015) showed clear associations between MA and the amount of
      salt intake (beta = 0.683, p < 0.002), saturated fatty acids (beta = 0.342, p =
      0.029) and the amount of consumed mono- and disaccharides (beta = 0.479, p =
      0.018). There was no significant association with the amount of protein intake
      (beta = 0.319, p = 0.152). Looking at the fatty acids in particular there were
      significant associations to MA with myristic acid, arachidonic acid and
      negatively with linoleic acid. Splitting the data in tertiles according to the
      amount of salt intake (I: < 6 g/d, II: 6-10 g/d, III: > 10 g/d) we could show in
      addition to the overall effect an intraindividual influence on the amount of MA
      (MA-means +/- SD: I: 45 +/- 56 micrograms/min., II: 61 +/- 59, III: 81 +/- 74, p
      < 0.001 between the groups). There were no significant differences between the
      groups in mean blood pressure, HbA1c and BMI.

PMID- 11512196
TI  - [Risk factors for increased plantar pressure in type 2 diabetes].
AB  - Diabetic foot ulcers develop at high pressure sites, whereby causal factors for
      increased plantar pressure are insufficiently investigated. We clinically
      inspected the feet of 186 Type 2-diabetic patients and measured peripheral
      neuropathy and plantar pressure during walking. Subjects were assigned into a
      group with normal (n = 113) and elevated (n = 73) plantar pressure. In patients
      with elevated plantar pressure body weight was significantly increased (85.4 +/-
      12.3 kg vs. 80.7 +/- 13.8), as was plantar pressure increased at the hallux (519
      +/- 322 kPa vs. 346 +/- 154), at the metatarsal head I (MTH) I (442 +/- 270 vs.
      235 +/- 95) and at the MTH II-V (788 +/- 277 vs. 446 +/- 145). The vibration
      perception threshold was significantly higher among these patients (21.8 +/- 11.0
      Volt vs. 16.7 +/- 9.0), as was the prevalence of hyperkeratosis (69.9% vs. 43.4)
      and clawed toes (28.8% vs. 15.9). In a multiple regression analysis,
      hyperkeratosis (Beta = 0.25, p < 0.001) and body weight (Beta = 0.27, p < 0.001)
      were significant risk factors, but did not describe the whole variation of
      plantar pressure in the multivariate model. Limited joint mobility (LJM), which
      was not measured but estimated in the present study, was slightly more prevalent
      among patients with elevated plantar pressures (46.6 vs. 33.6%). It could be
      assumed, that LJM, if exactly measured, is a significant risk factor in a
      multivariate analysis, too.

PMID- 11512197
TI  - [Effect of limited joint mobility on plantar pressure in patients with type 1
      diabetes mellitus].
AB  - Limited joint mobility (LJM) in the foot as well as the relationship of LJM and
      plantar pressure have not been well examined in patients with Type 1 diabetes
      mellitus. Pronation of the foot during stance phase is helping to absorb the
      shock of impact. Pronation of the foot is inevitably connected with abduction and
      dorsiflexion of the foot. We investigated the relationship of LJM and plantar
      pressure in 50 patients with Type 1 diabetes mellitus (age 40 +/- 11 years,
      duration of diabetes 23 +/- 10 years, HbA1c 8.2 +/- 1.1%) and the differences in
      joint mobility between these patients and 44 nondiabetic controls (age 35 +/- 10
      years). Joint mobility was measured with a pocket-goniometer; plantar pressure
      was measured with a pedography platform during walking about barefoot.
      Statistical analysis showed a significant correlation between range of motion at
      the talocrural joint and the plantar pressure under the metatarsalheads 2-5, and
      at the right metatarsophalangeal joint 1 and the plantar pressure under the MTHs
      4-5 respectively in diabetic patients. That means, the smaller the range of
      motion, the higher the plantar pressure. The range of motion in diabetic patients
      was smaller at the talocrural and metatarsophalangealjoint 1 than in controls.
      Increase of plantar pressure can be caused by LJM because it impares the shock
      absorbing capability of the forefoot.

PMID- 11512198
TI  - [Donation for medical care at the Vienna Civic Hospital in the 15th century.
      Responsibility for daily rounds].
AB  - The medical treatment in the city hospital of Vienna, which was attached to the
      University as a teaching facility, was not of the best quality in the 15th
      century. A report by an unknown author describes the medical treatment as tending
      to lead to death rather than recovery. In 1436 a donation was made by Nicolaus
      Aichberger de Furstenfeld, a well known member of the Medical School of Vienna
      University, to engage a physician who had to visit the patients daily. The
      acceptance of the donation is not documented, but the research shows Michael
      Gruber, student of medicine, as possessor of the foundation. The obligation for
      daily medical treatment was a remarkable requirement for that time.

PMID- 11512199
TI  - Perinatal comfort and well-being as a developmental concept.

PMID- 11512200
TI  - Parent-child interactions and development of toddlers born preterm.
AB  - Fathers and mothers of 49 healthy preterm and 54 full-term infants were observed
      interacting with their child at 3 and 12 months using the Nursing Child
      Assessment Teaching Scale. Each parent completed the Parenting Stress Index at
      both times. At 18 months adjusted age, the children were assessed using the
      Bayley Scales of Infant Development, Sequenced Inventory of Communication
      Development-Revised, and MacArthur Communicative Development Inventory. Preterm
      children scored significantly lower on the Bayley Mental scale and on the number
      of words produced. Early parent-child interactions contributed to the child's
      development. Mother's interactions with the child, child gender, and family
      socioeconomic status predicted 17% of the variance in the Bayley Mental score.
      Mother's and father's interactions with the child, child gender, and the child's
      behavior with his or her mother predicted 22% of the variance in receptive
      communication skills.

PMID- 11512201
TI  - Proximal and distal correlates of maternal control style.
AB  - Control, as an aspect of maternal interaction, has been found to be an important
      component to optimal child development. Maternal control style is defined as a
      mother's tendency to be controlling or supportive of her child's autonomy. The
      relationship between two types of maternal characteristics, proximal and distal,
      and maternal control style was investigated in a sample of 184 mothers and their
      4-year-old children. Global ratings of videotaped data of two problem-solving
      tasks were made on a 5-point scale. An optimal maternal control style was
      associated with higher levels of the distal maternal characteristics of maternal
      education, age, occupation, and higher levels of the proximal characteristics of
      maternal responsivity and involvement. A hierarchical regression model explaining
      26% of the variance in maternal control style scores supports the importance of
      both types of maternal characteristics. The results are discussed in relation to
      the methodology and the theoretical framework of role.

PMID- 11512202
TI  - Perceived impediments to prenatal care among low-income women.
AB  - The study describes women's experience with prenatal care, their perceived
      impediments to care, and compares the impediments cited by the women with levels
      of care utilization. The sample consisted of 126 African American women. A
      structured interview and questionnaire were used. The results showed that
      pregnancy was unplanned in 78.6% of the women, and no one encouraged the women to
      obtain care in half the cases. Only 50.8% of the women made adequate utilization
      of prenatal care. The main impediments to care were transportation, long waiting
      time, having too many other problems, and fear of staff finding out about the
      women's use of substances. Five of the reported impediments significantly
      influenced the women's utilization of care. These were: substance abuse, fear of
      medical examination, the belief that prenatal care is not necessary, already knew
      of pregnancy, and no babysitter for other children.

PMID- 11512203
TI  - Parents call for concerned and collaborative care.
AB  - Parents' perceptions and expectations of health care providers within the context
      of the pediatric lung transplant experience were investigated using a
      phenomenological approach. Fifteen parents of 12 children were interviewed. Two
      theme clusters, concerned care and collaborative care, were formulated. Themes
      that reflected parents' perceptions of concerned care included: being treated as
      an individual, seeing familiar faces, feeling that their children really
      mattered, and conversely, experiencing a feeling of abandonment. Parents'
      perceptions of collaborative care included: being part of the team, and
      conversely, feeling caught in the middle. The theme cluster, concerned care,
      reflected the value parents place on continuity of care. Humanistic nursing
      theory provided the link between study results and nursing practice.

PMID- 11512204
TI  - Utilization and satisfaction with prenatal care services.
AB  - This study was conducted in St. Petersburg, Russia, under the auspices of the
      World Health Organization, Healthy Cities Project, and the St. Petersburg Healthy
      City Project. The purpose of this study was to investigate the predict use of
      prenatal care services (utilization) and satisfaction with the services. A high
      maternal mortality rate and low attendance at prenatal clinics brought this
      health care issue to the forefront of the St. Petersburg Healthy City Project
      agenda. Aday and Andersen's conceptual model was used to investigate use of and
      satisfaction with prenatal care services. Several characteristics of pregnant
      women were found to influence early use of prenatal care services and women's
      level of satisfaction. Need had no influence in explaining when women started
      prenatal care or satisfaction with the services. Lastly, there was no
      relationship between early use of prenatal care services and women's level of
      satisfaction with the services.

PMID- 11512205
TI  - Maternity care during the post-World War II Baby Boom: the experience of general
      duty nurses.
AB  - The purpose of this study is to describe maternity nursing during the post-World
      War II Baby Boom from the perspective of general duty nurses. During the Baby
      Boom, maternity care changed with medical advances and the highest birth rate
      ever in the United States. This study provides insight into the impact of context
      on nurses' work experiences. Seven general duty postpartum or nursery nurses were
      interviewed about their nursing experiences during the Baby Boom. Constant
      comparative analysis was used to synthesize the transcripts of the interviews
      into in-depth descriptions of participants' work experiences. The large numbers
      of mothers and babies in their care, the prevailing concerns for infections, and
      paternalism influenced these nurses' work. Expectations about and by the nurses
      as well as work relationships contributed to the nurses' acceptance and rejection
      of changes in care of mothers and babies.

PMID- 11512206
TI  - Two-year follow-up of AIDS education programs for impoverished women.
AB  - The long-term effects of two culturally competent AIDS education programs with
      different content on the risk behavior and AIDS-related knowledge of 410 homeless
      African American women 2 years after program completion were examined.
      Participants were members of a larger cohort of impoverished African American and
      Latina women recruited in Los Angeles from 1989 to 1991. Of a subsample of 527
      African American women selected randomly for a 2-year follow-up interview, 410
      (78%) were located and agreed to participate. Women participating in both AIDS
      education programs reported reduced HIV risk behaviors and demonstrated greatly
      improved AIDS knowledge at 2-year follow-up (p < .001). Women in a specialized
      program were less likely than those in a traditional program to report
      noninjection drug use at 2 years. Women in the traditional program had
      significantly better AIDS knowledge at follow-up (p < .001). These findings
      suggest that educational programs can produce sustained benefits among
      impoverished women.

PMID- 11512207
TI  - Culturally sensitive research methods of surveying rural/frontier residents.
AB  - This article describes adaptations to conventional survey research methods based
      on knowledge of and respect for characteristics and qualities of rural
      communities and rural culture. These culturally sensitive methods may have
      contributed to a high response rate in a population-based study of frontier
      residents conducted in one western state in the United States. Through these
      methods, residents' interests in the study was heightened and the study's
      visibility was increased. Adaptations were also necessary to compensate for
      shortcomings in the available sample frame for the rural population of interest.
      References on survey research by mail provide standards for generally accepted
      procedures but offer few guidelines for tailoring these approaches for varying
      cultures. Approaches based on the local culture of the persons to be surveyed can
      increase response rates as well as demonstrate respect for the culture of
      intended study participants.

PMID- 11512208
TI  - Use of a computer software program for qualitative analyses--Part 2: Advantages
      and disadvantages.
AB  - NUD.IST 3.0 was generally effective in managing the qualitative data of dyspnea
      stimuli. Yet, some disadvantages were found related to format restrictions of
      transcripts and data volume. In particular, an appropriate format of transcripts
      for NUD.IST use was critical for efficient data management. Awareness of
      strengths and limitations of program functions is necessary to use NUD.IST
      efficiently in qualitative data management.

PMID- 11512209
TI  - Garbage in, garbage out.

PMID- 11512210
TI  - A multidisciplinary concept analysis of quality of life.
AB  - The purpose of this article is to analyze how the concept of quality of life
      (QOL) is currently being defined and used within health care. An on-line search
      of the phrase QOL in Medline, Cinahl, Psyc-Info, Eric, and Social Science
      Abstract provided a list of 16,021 articles published between 1993 and 1998. A
      convenience sample of 65 research and theoretical articles from the 1990s was
      examined to determine current usage and definitions of the concept of QOL across
      disciplines. Analysis was conducted, and a definition of the concept QOL, based
      on the analysis, is offered.

PMID- 11512211
TI  - Axial coding and the grounded theory controversy.
AB  - The purpose of this article is to describe the similarities and differences
      between two approaches to grounded theory research: grounded theory as espoused
      by Glaser and grounded theory as espoused by Strauss and Corbin. The focus of the
      article is the controversy surrounding the use of axial coding. The author
      proposes a resolution to the controversy by suggesting that one does not need to
      view either approach as right or wrong; rather, the qualitative and grounded
      theory researcher can choose an approach, and that choice is based on the goal of
      the researcher's study. Examples of both approaches, from the author's research
      study on the experiences of living in a family with a child with attention
      deficit hyperactivity disorder (ADHD), are provided.

PMID- 11512212
TI  - Modeling the individual determinants of research utilization.
AB  - Despite more than two decades of investigation, our accumulated knowledge about
      what influences nurses' use of research is underdeveloped. This study's
      objectives were to develop and test a series of structural equation models that
      included individual factors believed to influence research utilization. Estimates
      of the models were obtained using maximum likelihood estimation. Model fit was
      assessed by examining chi-square, the adjusted goodness of fit index, and the
      standardized residuals. Within a simple model that permitted only direct effects
      and controlled for instrumental, conceptual, and persuasive research utilization,
      3 of 26 concepts exerted significant effects on research utilization. These were
      a positive attitude toward research, belief suspension, and in-services attended.
      These results support the assertion that our descriptive body of research on the
      determinants of research utilization is underdeveloped, limiting our ability to
      design and test effective strategies to increase the use of research findings in
      nursing practice.

PMID- 11512213
TI  - Research methodology issues related to interviewing the mechanically ventilated
      patient.
AB  - Difficulties conducting research in vulnerable or frail patient populations limit
      the data-based information on which to base practice in these populations.
      Although there are many challenges in this type of research, they are not
      insurmountable, and, in an effort to encourage others interested in studying
      vulnerable patient populations, we discuss the methodological process used to
      prospectively study one vulnerable group. Interviews about perceptions of
      weaning, fatigue, mood, and sleep/rest states were conducted with 20 patients who
      were chronically critically ill and required long-term mechanical ventilation.
      Illness severity and communication difficulties were primary considerations in
      the design, development, and implementation of the study. Ethical considerations,
      informed consent, sample representation, and data collection issues are
      discussed.

PMID- 11512214
TI  - The experiential meaning of well-being for employed mothers.
AB  - Employed mothers must constantly juggle and balance the multiple roles they face
      on a daily basis, which can be overwhelming and may adversely affect well-being
      and health. Findings are presented from a naturalistic-inquiry study that
      explored how employed mothers with preschool-age children experience positive
      well-being in their lives. Interviews were conducted with 16 mothers who worked
      full time and had at least one preschool-age child living at home. Findings
      included seven categories reflective of experiential well-being: mutuality,
      spirituality, child-centeredness, acceptance, happiness, security, and enrichment
      of the world. Results of this study are anticipated to contribute to a foundation
      for theory development and subsequent theory testing for promoting well-being.

PMID- 11512215
TI  - Defining the eligible, accessible population for a phenomenological study.
AB  - When a rare target population is the focus of a proposed descriptive,
      phenomenological study, it is important to project the size of the population
      that is both eligible to participate and accessible to the investigator. This
      estimate of the eligible, accessible population is one basis for judging the
      feasibility of a proposed phenomenological study, and it serves to establish a
      demographic framework for the analysis. While preparing a grant proposal for a
      phenomenological study of older widows' experience of home care, the author
      developed a method of estimating the eligible, accessible population. The
      philosophical rationale for the method is explained, and its procedures are
      detailed. Suggestions are given for adapting the method in keeping with the aims
      of a particular phenomenological study.

PMID- 11512216
TI  - [Reducing medical error and improving patient safety].
AB  - Within the last years in the public discussion medical error became a new issue.
      Several studies have addressed problems in the delivery of medical services,
      which create a breakdown of trust in doctors and the health care system. One of
      the reasons may be a broader and faster (global) information network system
      together with media which search extensively for mistakes and problems, despite
      the fact that diagnostic and therapeutic methods, skills and accuracy could be
      improved. Nevertheless, the medical system has to address these challenges in
      order to definitively reduce medical errors and improve patient safety. In
      contrast to the discussion about quality assurance and management systems in
      health care, medical errors and patient safety do not have the smell of expensive
      or not really necessary products, but they are urgent and very important. So the
      topics "medical error" and "patient safety" have in fact the potential to enhance
      quality management systems (QMS), which are an accepted technology to solve these
      problems.

PMID- 11512217
TI  - [Overview of medical errors].
AB  - The physician is under the legal obligation to his patient to conduct a
      professional treatment that is optimally suited to obtain the wanted recovery. A
      violation of this and the equally existing obligation to observe the due
      diligence is termed malpractice. The degree of diligence necessary is determined
      in accordance to the behaviour deemed the standard in certain circles of
      conscientious and attentive physicians or specialists. The virtual knowledge and
      capability of the single physician is not referred to. The relevant standard of
      diligence as well as the medical standard do not affect the doctor's free choice
      of treatment but they set the conditions under which an alternative therapy
      deviating from the standard can be resorted to. Malpractice can be classified
      into different groups of instances, i.e. diagnostic mistake/violation of the
      obligation to put down a record of the examination's results, bad choice of
      therapy, or inadequate organization. A particular example of such inadequate
      organization is the performance of an operation by an inexperienced physician.
      Provided that a correction of the damage to health or its expansion/manifestation
      can be prevented the doctor is legally compelled to reveal the malpractice to his
      or her patient. If the malpractice causes any injury to the patient's health
      damages can be requested on the basis of contractual as well as tort claims
      including compensation for suffering from injuries itself. Apart from the
      consequences related to civil law malpractice can entail repercussions under
      penal law. To avoid the reproach of behaviour in contradiction to the exigencies
      of due diligence every physician is required to ask himself the question whether
      he possesses the professional abilities to conduct the requisite treatment.
      Furthermore, he has constantly to strive for a continuation of his profession
      related learning.

PMID- 11512218
TI  - [Quality management of severely injured patients].
AB  - The process of care of a severely injured patient from the site of the accident
      up to rehabilitation is complex and the result may be influenced by many factors.
      The outcome of the patient is determined by the primary injury caused by the
      accident but also by the secondary injury which is influenced by the quality of
      the diagnostic and therapeutic procedures. Different studies observed a negative
      correlation between the duration of diagnostic procedures in the initial phase in
      the emergency room and the outcome of the patient. It could be shown that a
      standardized documentation of emergency room procedures and the discussion of the
      resulting data in quality circles contributed to an improved survival of
      patients. Beside these internal quality circles the trauma registry of the German
      Trauma Society provides the possibility of external comparison.

PMID- 11512219
TI  - [Incident reporting as a tool for error analysis in medicine].
AB  - Incident Reporting is a tool for error analysis that has its tradition in high
      risk industries such as aviation, nuclear power plants or the chemical process
      industry. The main purpose is to detect insufficiencies in the system as well as
      in the individual process of each enterprise. In medicine, incident reporting has
      only rarely been used for error analysis. Pioneering is the domain of
      anaesthesiology when it comes to apply this tool. In this report the method of
      incident reporting is described in general with its indications, requirements as
      well as its limitations. Furthermore a model for the definition of a critical
      incident in medicine is described and the first conclusions out of a national
      program of incident reporting in Switzerland are given.

PMID- 11512220
TI  - [Complications in internal medicine. A study for clinical epidemiology and for
      prevention of medical complications in Swiss hospitals].
AB  - The committee of the heads of the swiss hospital departments of internal medicine
      are conducting a study for the prospective registration of complications of
      medical interventions in patients treated in hospitals. The objective is the
      reduction of complications by means of postgraduate and continuing education of
      the hospital staff and by organisational measures. The kind and number of all the
      interventions performed in each patient and the respective complications are
      registered by a means of multiple choice form. With this method the percentage of
      complications can be calculated for each kind of intervention and therefore is
      also a contribution to the clinical epidemiology of complications. The data are
      collected anonymously and regular feedback information on pertinent statistic and
      casuistic material from all the hospitals is provided to all the participants.
      The casuistic information is commented on by a group of experts. The results
      demonstrate that the study is well practicable and from 1998 to 2000 42,000
      patients have been evaluated.

PMID- 11512221
TI  - [Patient security through algorithm standardization in a urology practice-
      account of practical experience and medical certification].
AB  - Visiting a physician means taking a risk, of which our patients (clients) know
      too little. Those who run the practice know about critical points and have the
      duty to protect their clients. One way of doing so is to standardize working
      routines. An even better way is to have the practice certified and audited
      (controlled) annually by an objective institution (e.g., the German TUV).

PMID- 11512222
TI  - ["Clinical medicine will be a science or it will not be," Observations on
      evidence-based medicine and its critique by Rogler and Scholmerich (2000)].
AB  - During its short life time evidence-based medicine (EbM) has been subject of
      partly fierce criticism, mainly from the side of the clinic. In Germany, Rogler
      and Scholmerich (September 2000) published a critical commentary on EbM in the
      Deutsche Medizinische Wochenschrift. Our text is intended as a rejoinder. It
      firstly aims at clarifying the concept of EbM, especially its contribution to the
      science of clinical medicine, and it secondly answers relevant details of Rogler
      and Scholmerich's criticism. Their text turns out to be a mixture of truly
      relevant remarks, exaggerations, misunderstandings and obvious errors.

PMID- 11512223
TI  - [Development of an evidence-based questionnaire for evaluating the structural
      quality of providers].
AB  - The goal of this paper is to present the method used to develop an evidence-based
      questionnaire for the evaluation of the structural quality of provider
      institutions. Structural features addressed in the questionnaire are validated by
      study-based evidence for a relationship with improved outcome quality. For the
      purpose of identifying relevant studies, a systematic review and evaluation of
      the literature was performed. The questionnaire contains the following items:
      continuous medical education with interactive elements (yes/no); use of evidence
      based clinical practice guidelines (yes/no); implementation of a computer alert
      system to prevent injury from adverse drug events (yes/no); and annual diagnosis-
      or procedure-specific volumes for each department, providing physician, and
      senior consultant (threshold volume met or not).

PMID- 11512224
TI  - [Usefulness and necessity of unsynchronized photosolotherapy and bath-PUVA--two
      variants of balneophototherapy--in funded ambulatory health care].
AB  - The Standing Committee of Statutory Health Insurance Physicians and Sickness
      Funds is the legal body that makes decisions on reimbursement for health care
      services in the German ambulatory health care sector. In 1994 the committee
      declined the reimbursement of balneophototherapy. Balneophototherapy comprises a
      bath in a saline solution followed by ("non-synchronous") or simultaneous
      ("synchronous") UVB-irradiation. Photochemotherapy with bath-water delivery of
      psoralens combined with UVA light is also covered by the term balneophotherapy.
      The main indication for both procedures is serious psoriasis. Bath PUVA was also
      recommended for atopic dermatitis, pityriasis lichenoides, lichen ruber and
      mycosis fungoides. An effectiveness study sponsored by the sickness funds with
      rather poor methodological design and conduct was not able to show an unbiased
      effect of balneophototherapy despite inclusion of thousands of patients. On the
      contrary, a poor adherence of patients and doctors was documented, since 63% of
      patients suffering from psoriasis and treated with saline bath followed by UVB
      irradiation stopped early or used additional therapies like cortisone or vitamin
      D3 derivatives. Only 43% of patients suffering from psoriasis and treated by bath
      PUVA did not stop the initial therapy and did not receive additional therapy
      (UVB, cortisone). In addition, the committee also conducted a thorough review of
      the literature, guidelines and status in other health care systems. Finally the
      two modifications of balneophototherapy were again declined from reimbursement in
      the German ambulatory health care sector. There were no controlled clinical
      trials showing efficacy of saline bath followed by UVB irradiation. Up to now
      bath PUVA was only evaluated in small equivalence trials which despite the fact
      that a drug was tested did not apply basic ICH standards (international
      conference on harmonisation) for equivalence trials. Additionally, the long-term
      cancer risk inherent to the application of psoralenes must be considered. Since
      the definition of "severe psoriasis" is not trivial a wide use of bath PUVA in
      ambulatory health care has to be based on the results of rigorously conducted
      clinical trials showing the effectiveness, safety and appropriateness in
      comparison to other treatment modalities. In reaction to the decision of of the
      committee two randomised controlled trials for the evaluation of the efficacy of
      balneophototherapy are planned.

PMID- 11512225
TI  - [The filmless hospital--hopes fulfilled?!]].

PMID- 11512226
TI  - [MRI and MR spectroscopy after silicone breast implants in the female breast].
AB  - This paper reviews the evaluation of the breast of women by MR-techniques after
      implantation with silicon gel protheses. The main topics are the diagnosis of
      implant defects such as extensive "gel bleed" and intra- and extracapsular
      ruptures. Moreover, the MR-detection of siliconomas (encapsulated silicone) and
      differentiation from malignomas as well as MR-features of chronic foreign body
      reactions are presented. "Gel bleed" is difficult to diagnose unambiguously by
      MRI alone. The "linguini" sign is the only reliable mans to diagnose
      intracapsular ruptures. The presence of silicone outside the implant capsule
      indicates extracapsular rupture. The MR-spectroscopic detection of silicone in
      the liver suggests after short implantation times and a normal MR scan the
      diagnosis "gel bleed", and after longer implantation times of more than 10 years
      and missing "linguini" sign the diagnosis of ruptures due to a dissolved shell of
      the implant. MRI, in comparison to other imaging modalities, has the highest
      specificity and sensitivity in the diagnosis of implant defects. Due to its high
      costs, however, MR is not suitable as a screening tool and should only be used in
      cases of sonographic suspected rupture or after radical mastectomy. In these
      cases MRI is the method of choice.

PMID- 11512227
TI  - Percutaneous translymphatic thoracic duct embolization for treatment of
      chylothorax.
AB  - A modified technique for transabdominal, translymphatic occlusion of the thoracic
      duct is described. During unilateral lymphangiography an abdominal lymph vessel
      was punctured with a fine needle under fluoroscopic guidance, and a 4 French
      access to the lymph system established. The thoracic duct was successfully
      embolized with coils and tissue adhesive in a patient with postoperative high
      output chylothorax. Chylous drainage immediately decreased after the
      intervention, the intercostal drain could be removed after seven days. Long term
      follow up over a ten months period confirmed the clinical success; the patient is
      still free of pleural effusions.

PMID- 11512228
TI  - [Interobserver variability in CT of oro- and hypopharyngeal carcinomas].
AB  - PURPOSE: To evaluate the inter- and intraobserver reproducibilities of computed
      tomography (CT) in patients with oro- and hypopharyngeal carcinomas. METHODS: Two
      independent readers interpreted the CT images of 41 patients with hypopharyngeal
      carcinomas, 45 patients with oropharyngeal carcinomas, and 23 patients without a
      tumor. All relevant subregional anatomic structures were evaluated for the
      presence of tumor infiltration. Statistical analysis was done by using Cohen's
      kappa and the Wilcoxon test; subregional prevalences, sensitivities, and
      specificities were also determined. RESULTS: Mostly, especially for clinically
      relevant subregions, moderate and substantial inter- and intraobserver
      reproducibilities were determined (range of the determined kappa values: 0.25
      1.00). The kappa values of the intraobserver reproducibilities of both readers
      were not significantly different (P = 0.20). The kappa values of the
      intraobserver reproducibilities were in almost all the cases higher than the
      respective kappa values of the interobserver reproducibility. CONCLUSION: CT of
      oro- and hypopharyngeal carcinomas can be interpreted with clinically acceptable
      variability. A higher agreement can be achieved if repeated interpretation is
      done by a single person.

PMID- 11512229
TI  - [Use of a portable CT scanner for monitoring ventilated patients in an intensive
      care unit].
AB  - PURPOSE: Evaluation of postoperative pulmonary atelectasis using a portable
      computed tomography (CT) unit. MATERIAL AND METHODS: 5 spiral CT-examinations in
      low-dose technique were performed on each of 10 patients with partial pulmonary
      atelectasis after coronary bypass surgery. The patients were artificially
      ventilated using different levels (0 to +15 cm H2O) of positive end-exspiratory
      pressure (PEEP). The changes in atelectatic volumes were determined for each
      side. RESULTS: In 6 patients the primary volume of atelectasis was larger on the
      left side than on the right. Atelectatic volumes decreased with increasing PEEP.
      Re-expansion of atelectases was significantly (p < 0.01) better with a PEEP of
      +15 cm H2O. CONCLUSION: Computed tomography allows visualisation of postoperative
      atelectasis reliably, even in the low-dose technique. Concordantly, additional
      therapeutically relevant side findings can be detected compared to conventional
      chest X-ray. Risky patient transport becomes unnecessary.

PMID- 11512230
TI  - [Clinical value of native and contrast enhanced MRI in staging prostatic
      carcinoma before planned radical prostatectomy].
AB  - PURPOSE: To assess the clinical value of MRI with and without contrast agent in
      the staging of prostatic carcinoma. Relevance for surgical management. METHODS:
      60 patients with carcinoma proven by biopsy or suspected prostatic carcinoma were
      evaluated with MRI. The examinations were performed in a 1.5 T (Philips ACS-NT
      Gyroscan) imager with multiplanar orientations before and after intravenous
      application of 0.1 mmol/kg/bw Gadodiamide (Omniscan-Nycomed/Amersham). The gold
      standard was histology after radical prostatectomy and in case of non-operability
      the consensual final staging. RESULTS: Compared to histology MRI revealed a
      sensitivity of 75% and a specificity of 82% in the differentiation of locally
      advanced carcinoma (T 3/4). Including the non-surgical cases MRI showed a
      sensitivity of 82.5% and a specificity of 86%. Interindividual analysis showed no
      difference in diagnostic accuracy between the non-enhanced and the contrast
      enhanced techniques. In 23% of cases (n = 14) MRI induced changes in patient
      management. CONCLUSIONS: MRI is an accurate procedure in the local staging of
      prostatic carcinoma. In combination with clinical findings, PSA, and grading
      scores MRI has a significant influence on treatment selection. Contrast agent
      administration does not seem to increase the diagnostic accuracy significantly.

PMID- 11512231
TI  - [Contribution of MRI in diagnosis of urinary stress incontinence without
      concomitant urogenital prolapse].
AB  - PURPOSE: To detect pathomorphological changes of the pelvic floor, the vagina,
      and the urethra by MR imaging in patients with stress urinary incontinence in the
      absence of organ descent compared with findings in 10 healthy controls. MATERIALS
      AND METHODS: The study included 10 healthy controls and 38 patients with stage II
      urinary incontinence showing no urge symptoms but a pathological stress profile
      on urodynamic testing. The subjects underwent MR imaging with a phased-array coil
      at 1.5 T in addition to urodynamic testing and gynecological examination. The
      following sequences were used: axial and coronal PD-weighted TSE sequences with a
      FOV of 20 cm and a section thickness of 4 mm; axial STIR sequence. Sagittal T2
      weighted HASTE sequences were acquired during pelvic floor contraction,
      relaxation, and straining maneuvers. RESULTS: In 22/38 cases pathomorphological
      changes were found by MR imaging. The pathomorphological changes were classified
      as lateral defects (n = 14) if the musculofascial connection between the levator
      muscle and the lateral vaginal wall or the butterfly shape of the vagina was
      absent and as central (n = 16) if changes were detected in the urethral wall.
      Defects of the pelvic floor muscles were detected in 8 cases. No underlying
      changes were identified in 16/38 cases. CONCLUSION: In cases of female urinary
      incontinence, MR imaging of the pelvic floor can detect pathomorphological
      changes, which are difficult to identify by clinical examination. MR imaging
      currently does not allow the detection of morphological changes in all forms of
      female urinary stress incontinence.

PMID- 11512232
TI  - [Transcatheter embolization of pulmonary arteriovenous fistulas].
AB  - AIM: Evaluation of technical success, complications and long-term results of
      transcatheter coil embolisation in pulmonary arteriovenous malformations (pAVMs).
      MATERIAL AND METHODS: Transcatheter embolisations of 46 pAVMs in 14 patients were
      analysed retrospectively, and, 5 years after treatment, the patients were
      interviewed by telephone concerning persistent symptoms and complications. Main
      symptoms before embolisation were dyspnoe (86%), hypoxaemia (100%), cerebral
      ischemia (21%), and hemoptysis (14%); 11 patients (79%) suffered from hereditary
      hemorrhagic telangiectasia. RESULTS: Embolisation with an average of 3.9 coils
      (min. 1, max. 19 coils) per pAVM yielded technical success in all cases. Only two
      minor complications, transitory pleuritis and a small lung infarction were
      observed. On follow up examination after 5 years either no residual complaints or
      substantial improvement of dyspnoe were reported; no patient suffered from
      neurologic or hemorrhagic complications after the embolisation. CONCLUSION:
      Transcatheter embolisation is a safe and minimally invasive therapy for pAVMs and
      has rightfully replaced surgical resection as the therapy of choice.

PMID- 11512233
TI  - [Evaluation of an electromagnetic virtual target system (CT-guide) for CT-guided
      interventions].
AB  - PURPOSE: Evaluation of the accuracy of a new electromagnetic target system for
      interventional CT-guided procedures with virtual navigation in a previously
      acquired helical CT. MATERIAL AND METHODS: The new target system CT-Guide 1010
      (Ultraguide, Tirat Hacarmel, Israel) for CT-guided interventions was adapted to
      the video signal of the Somatom Plus 4 and Volume Zoom (Siemens, Erlangen,
      Germany). A helical CT-dataset including skin-based sensor cubes was transferred
      to the integrated navigation system inside the scanner room. 50 image-guided
      interventions and biopsies were performed outside the gantry using virtual
      navigation to reach the lesion. The accuracy of the procedures was evaluated
      using documentation of the needle tip with CT-fluoroscopy, results of histology,
      and follow-up. RESULTS: The deviation between planned and documented needle tip
      was 2.2 +/- 2.1 mm in 50 procedures. Time between the end of planning-CT and
      needle positioning using the system was 13 minutes. There were no complications
      due to the use of the system. CONCLUSION: The CT-Guide allows for virtual real
      time navigation with high accuracy. Advantages are the free needle angulation
      without gantry tilt, use of optimal CT perfusion phase for virtual navigation,
      and reduction of radiation exposure to the patient and interventionalist.

PMID- 11512234
TI  - [Treatment of para-ostium renal artery stenoses with a new, solidly premounted
      balloon expandable stent].
AB  - PURPOSE: Evaluation of the handling, technical success rate, and six-months
      patency rate of a new, premounted balloon-expandable stent in ostial renal artery
      stenoses. MATERIAL AND METHODS: In a prospective study, 27 ostial renal artery
      stenoses in 20 patients were primarily treated with the new "Renal Bridge Stent"
      (Medtronic AVE, Dusseldorf). All patients had a history of hypertension and 8
      patients had renal dysfunction. The handling and visibility of the stent was
      scored on a three grade scale by the operators. Follow-up angiography including
      intra-arterial trans-stenotic pressure measurements was performed in 23 out of 27
      stenoses (17 patients). RESULTS: Handling and visibility were scored as good by
      all operators. 26 of 27 stenoses were treated with technical success by
      implantation of 28 stents. The mean degree of stenosis was reduced from 74.2% to
      less than 5%. At 6 months, 8 stents out of 23 (35%) showed a significant in-stent
      stenosis (stenosis degree > 50% and intra-arterial pressure gradient > 10 mmHg).
      The stenosis rates were 63% using 5-mm stents, 30% using 6-mm stents, and 0%
      using 7-mm stents. CONCLUSION: Endovascular treatment of ostial renal artery
      stenosis with the used stent is safe and effective. The new stent shows a good
      handling and visibility. The high rate of in-stent stenoses might be explained by
      the rigid follow-up protocol including angiography, trans-stenotic pressure
      measurements, and the high number of 5-mm vessels in our study.

PMID- 11512235
TI  - [The Straub-Rotarex thrombectomy system: initial experiences].
AB  - BACKGROUND: To evaluate the efficacy, safety and limitations of a new rotational
      thrombectomy device (Straub-Rotarex) in clinical practice. MATERIAL AND METHODS:
      The Straub-Rotarex catheter is a new, wire-guided rotational thrombectomy device
      for the treatment of acute and subacute occlusions of the femoro-popliteal
      arteries. Over a 6-month period, 28 patients (64% male, mean age 69 +/- 9.5, 51
      91 years) with 31 legs, mean duration of occlusion 4.4 +/- 4 (0-20) weeks, mean
      occlusion length 22 +/- 11 (5-40) cm were treated with the device, 5 of them in a
      cross-over technique. Target lesions: Aortic-femoral bypass, common iliac artery,
      external iliac artery, common femoral artery: 1 each, superficial femoral artery:
      23, popliteal artery: 17. Initial stage of claudication: IIa: 6%, IIb: 72%, III:
      16%, IV: 6%. RESULTS: Primary success rate: 90% (ipsilateral: 100%, cross-over:
      40%). Stage of claudication after intervention: I: 85%, IIa: 7%, III: 4%, IV 4%,
      one amputation. 3-months follow-up: stage I: 86% (n = 24), IIa: 14% (n = 4), one
      femoro-popliteal bypass. Restenosis rate 18%. 6-months follow-up: stage I: 56% (n
      = 9), IIa: 31% (n = 5), IIb: 13% (n = 2). Restenosis rate 56%. COMPLICATIONS: 32%
      (5 perforations, three cases of embolism after PTA, one wire-induced dissection,
      one retroperitoneal bleeding coming from the puncture site). CONCLUSIONS: The new
      device is a useful tool for the treatment of (sub)acute long-distance occlusions
      of the SFA and popliteal artery and in-stent restenosis as well in antegrade
      technique. Main complications are perforations. Cross-over interventions can only
      be done in special cases.

PMID- 11512236
TI  - [Cryotherapy of malignant tumors: studies with MRI in an animal experiment and
      comparison with morphological changes].
AB  - PURPOSE: Aim of our study was to investigate the efficacy of 7 F cryoprobes for
      percutaneous use morpho- and histologically, to examine the role of apoptosis
      after cryotherapy, and to compare contrast-enhanced MRI with histopathological
      findings at different time intervals in a tumor-mouse model. METHODS:
      Percutaneous cryotherapy was performed in 15 immunocompromised nude mice with
      subcutaneously implanted tumors using the non-small-cell lung cancer cell line Lu
      1. In group a) 7 mice were sacrificed after definite time intervals and
      histological examinations were done for evaluation of necrosis and apoptosis (HE;
      TUNEL assay); 2 mice are in long-term follow-up. In group b) in 6 mice tumor
      destruction and perfusion before and after freezing were investigated with native
      and contrast-enhanced MR imaging (T1- and T2-weighted spin-echo) and compared
      with histopathological findings. Histological control were done in 2 untreated
      mice. RESULTS: We observed fast tumor-reduction within two weeks (ca. 50%). On
      long-term follow-up (> 6 months) no recurrence has been noticed so far. Tumors
      were well vascularized prior to treatment and did not-show contrast enhancement
      an any time after cryotherapy. A narrow contrast-enhanced zone was seen on the
      tumor border subcutaneously as a sign of peripheral hyperemia and central
      vascular stasis after cryotherapy. On histology there was evidence of both
      apoptosis and necrosis. CONCLUSION: We have established a tumor-mouse model for
      further investigations. Two minutes freezing of a 2-cm tumor in the mouse model
      is sufficient for tumor ablation with scarred healing. Apoptosis may play a role
      in cryotherapy of experimental tumors. Contrast-enhanced MRI is suitable for the
      estimation of the cryolasion.

PMID- 11512237
TI  - [Native magnetic resonance tomography imaging of the Morris hepatoma (MH-7777A)
      in the rat].
AB  - Goal of the study presented was to establish an oncological animal model for
      implantable and differentiated hepatoma in the rat and to evaluate imaging of the
      tumor induced using MRI. MATERIAL AND METHODS: 20 male buffalo rats underwent
      tumor cell implantation of 150,000 MH7777-A cells via laparotomy. After 12 days
      MRI was performed T1w SE, T2w TSE fs, TIRM) for tumor detection and measurement
      of size. Immediately there after all rats were killed and macroscopic and
      histological examination performed. Pathological findings were correlated with
      MRI. RESULTS: In 5 out of 20 animals no tumor was found. Mean size of the
      hepatomas in 15 animals was 3.1 mm (+/- 1.7 mm). On MRI 14 out of 15 tumors were
      detectable. Mean diameter in MRI was 2.7 mm (+/- 1.5 mm; 1-5 mm). T2w TSE was
      superior for tumor detection compared with the TIRM, while the best anatomic
      depiction was offered by T1w SE. CONCLUSIONS: The MH7777-A tumor model presents
      with a rate of 75% even with the small tumor cell amount of 150,000 cells. With
      MRI using T2 weighted sequences with fat saturation a detection of tumors with
      diameters of 1 mm is reliably possible in 93% of the cases.

PMID- 11512238
TI  - [Radiation exposure in single slice and multi-slice spiral CT (a phantom study)].
AB  - PURPOSE: The purpose of study was to compare patient dose applying singleslice-
      and multislice-spiral CT. METHODS: The examinations were performed with a
      singleslice-spiral CT (Highspeed Advantage; GE Medical Systems; Milwaukee, USA)
      and with a multislice CT systems (LightSpeed QX/i GE Medical Systems; Milwaukee,
      USA). For the determination of the radiation exposure (absorbed dose) a selection
      of most executed protocols (thorax-helical, abdomen-helical, petrous bone-axial,
      head-axial) were simulated using an Alderson Rando Phantom. The dose was
      determined by means of lithiumfluorid-thermoluminiscence dosimeters (TLD-GR 200).
      RESULTS: For thorax and abdomen protocols higher energy dose values could be
      found using a multislice CT. On the average the energy dose values were increased
      by 2.6 on an average in relation to single slice spiral CT. The energy dose
      values of the multisclice CT using head protocols could be reduced by 30% in
      relation to single slice spiral CT due to suitable parameter selections. The
      energy dose applying a petrous bone protocol resulted in an average increase by a
      factor 1.5 using a multislice CT. CONCLUSION: Using the new multislice CT
      technique protocol strategies must be optimized regarding the patient doses.
      Users can operate critically in the sense of the radiation protection only if
      they are aware of the occurring dose amounts to the patient.

PMID- 11512239
TI  - [Hybrid 3-D rendering of the thorax and surface-based virtual bronchoscopy in
      surgical and interventional therapy control].
AB  - PURPOSE: The aim of this study was to demonstrate the possibilities of a hybrid
      rendering method, the combination of a color-coded surface and volume rendering
      method, with the feasibility of performing surface-based virtual endoscopy with
      different representation models in the operative and interventional therapy
      control of the chest. MATERIAL AND METHOD: In 6 consecutive patients with partial
      lung resection (n = 2) and lung transplantation (n = 4) a thin-section spiral
      computed tomography of the chest was performed. The tracheobronchial system and
      the introduced metallic stents were visualized using a color-coded surface
      rendering method. The remaining thoracic structures were visualized using a
      volume rendering method. For virtual bronchoscopy, the tracheobronchial system
      was visualized using a triangle surface model, a shaded-surface model and a
      transparent shaded-surface model. RESULTS: The hybrid 3D visualization uses the
      advantages of both the color-coded surface and volume rendering methods and
      facilitates a clear representation of the tracheobronchial system and the complex
      topographical relationship of morphological and pathological changes without loss
      of diagnostic information. Performing virtual bronchoscopy with the transparent
      shaded-surface model facilitates a reasonable to optimal, simultaneous
      visualization and assessment of the surface structure of the tracheobronchial
      system and the surrounding mediastinal structures and lesions. CONCLUSIONS:
      Hybrid rendering relieve the morphological assessment of anatomical and
      pathological changes without the need for time-consuming detailed analysis and
      presentation of source images. Performing virtual bronchoscopy with a transparent
      shaded-surface model offers a promising alternative to flexible fiberoptic
      bronchoscopy.

PMID- 11512240
TI  - [Functional capacity of MRI-compatible biopsy needles in comparison with
      ferromagnetic biopsy needles. In vitro studies].
AB  - PURPOSE: Comparative evaluation of specimens obtained with different MR
      compatible biopsy systems and a conventional ferromagnetic system. METHODS:
      Biopsies of a pig liver were performed post-mortem with three different MR
      compatible (Somatex; E-Z-EM; Daum) and one conventional biopsy system (Somatex),
      five with each device. The specimens were measured and the histopathological
      quality was graded on a scale from 0 (no tissue) to 9 (best). The tip of the
      needle was examined with an electron microscope before and after biopsy to
      demonstrate abrasion. RESULTS: The histopathological score between the first and
      fifth specimen taken with one biopsy device showed no significant difference. The
      conventional system yielded significantly better results in nearly all categories
      (p < 0.05) than the MR-compatible biopsy systems. The areas of the specimens
      obtained with the MR-compatible biopsy systems (4.27-5.99 mm2) were significantly
      smaller than those from the conventional system (9.98 mm2). The needle tip
      abrasion of the different biopsy systems determined by electron microscopy showed
      no substantial difference. CONCLUSION: Specimens obtained with MR-compatible
      biopsy systems compared to conventional biopsy systems are of lower
      histopathological quality. This might be caused by a smaller side notch of the MR
      compatible biopsy devices. There was no difference in abrasion of the needle tip
      due to the softer, non-ferromagnetic alloys.

PMID- 11512241
TI  - [Pyogenic liver abscess: interventional versus surgical therapy: technique,
      results and indications].
AB  - For the therapy planning of liver abscesses both etiological factors and clinical
      symptoms have to be evaluated, with visualization via ultrasound, CT, or MRI. The
      indication for a percutaneous abscess drainage (PAD) is a solitary or complicated
      abscess with a safe drainage access. The success rate varies between 70 and 93%,
      the mortality rate between 1 and 11%. For complex abscesses, surgical therapeutic
      techniques (OSD) or liver resection have to be discussed. The OSD success rate
      varies between 51 and 70%, the mortality rate between 11 and 43%. In summary PAD
      is characterized by low complication and mortality rates, reduced risk of
      anesthesia, low cost, and short stay in the hospital.

PMID- 11512242
TI  - [2 cases of exclusively submucous atypical carcinoid of the supraglottic larynx.
      What is the value of sectional imaging?].

PMID- 11512243
TI  - [Coincidence of angiomyolipoma of the liver and kidney].

PMID- 11512244
TI  - [Cholesterol granuloma of the petrous tip: a by CT and MRI reliably identifiable
      lesion].

PMID- 11512245
TI  - [Comment on: Radiological evaluation of segmental decrease in height in acute and
      chronic degenerative lumbar intervertebral disk changes]].

PMID- 11512246
TI  - [Comparison of intraocular lenses--a review].
AB  - The wide array of intraocular lenses (IOLs) commercially available today makes it
      a formidable challenge to choose the most appropriate lens for the patient. Many
      wonder whether there truly are clinical differences among various IOLs. This
      update traces the evolution of IOLs in response to the widespread acceptance of
      phacoemulsification, and discusses the respective advantages and disadvantages of
      the IOLs available today based on clinical investigations.

PMID- 11512247
TI  - [Biochemical stress monitoring during cataract surgery; phenylephrine 10% shows
      no changes in serum-catecholamines in comparison with phenylephrine 5%].
AB  - BACKGROUND: There is a controversy about the concentration of topical
      phenylephrine recommended for diagnostic or therapeutic mydriasis. Phenylephrine
      10% leads to a faster and more pronounced mydriasis but cardio-vascular side
      effects like hypertension and arrhythmia have been reported. A maximal pupillary
      dilatation is a prerequisite for successful cataract surgery. The aim of this
      study was to evaluate the risk-benefit ratio of phenylephrine 10% in comparison
      to 5% in the daily practice of the cataract-surgery unit in our clinic by
      clinical assessment and monitoring of biochemical stress parameters. PATIENTS AND
      METHODS: 30 informed and consenting patients were randomly allocated to 2 groups
      of equal size. After a single application of 2 drops of phenylephrine 5% in group
      1 and 10% in group 2 respectively and 1 drops of cyclopentolate 1% with neutral
      pupil (time 0), an ECG was recorded and blood pressure, pulse, oxygen-saturation
      and pupil size were measured. Simultaneously a blood-sample was taken and the
      serum-catecholamines adrenaline and noradrenaline were determined by HPLC (High
      Pressure Liquid Chromatography). These measurements were repeated after 5, 10 and
      30 minutes. RESULTS: The mean pupil area after 30 minutes in group 1 was 31.97
      (+/- 0.43) mm2 compared to 45.72 (+/- 0.39) mm2 in group 2. Our data showed no
      other significant variation between the groups: neither clinical monitoring nor
      catecholamine measurements showed concentration-dependent patterns in blood
      pressure development or serum levels. No systemic cardiovascular effects were
      observed. CONCLUSION: These results demonstrate that a controlled application of
      phenylephrine 10%--under observation of contraindications--yields no increased
      risk for the occurrence of cardio-vascular side-effects in comparison with
      phenylephrine 5%. Therefore, we recommend the use of phenylephrine 10% in the
      described dosage as routine medication for cataract surgery.

PMID- 11512248
TI  - [Standardized semiquantitative analysis of corneal neovascularization using
      projected corneal photographs--pilot study after perforating corneal keratoplasty
      before immune reaction].
AB  - BACKGROUND: A semiquantitative scheme for analysis of corneal neovascularization
      using projected corneal photographs is demonstrated and tested in a pilot study
      to analyze occurrence of corneal neovascularization in patients after perforating
      keratoplasty which subsequently developed transplant rejection. METHODS: Corneal
      photographs on the slit lamp with diffuse frontal illumination were obtained in a
      standardized technique. Slides were projected with 100 x magnification and
      analyzed twice with a 2 months interval. Corneal vessels were graded by two
      independent observers in each of 12 corneal sectors in a standardized fashion
      (grade 0: no vessels beyond limbus, 1: vessels between limbus and outer end of a
      double-running diagonal suture; 2: vessels between outer suture end and graft
      host junction; 3: vessels reaching graft-host junction; 4: vessels within donor
      cornea). All patients with endothelial graft rejection of the prospective
      Erlangen non-high-risk keratoplasty study were included in a pilot study (1/1997
      6/2000: 13 of 325; 4%). One patient without photographs available was excluded.
      Corneal photographs taken prior to surgery (n = 10), at the last 3 monthly
      routine control before (10), at rejection episode (12) and one year later (10)
      were evaluated for corneal neovascularization. RESULTS: Interobserver correlation
      at the two assessments was 0.79 and 0.86 (Kendall's Tau B). Correlation between
      the assessments at the two analyses 2 months apart was 0.8. New vessels with
      diameter up to 6 microns can be detected. 8 of 12 analyzed patients (67%) with
      immune reaction after keratoplasty developed corneal neovascularization within 1
      year after operation prior to transplant rejection in at least one corneal sector
      (2.1 +/- 1.9 sectors; 1-6). At time of rejection, new vessels reached the graft
      host junction in 2 patients, in 1 patient vessels grew into the donor cornea,
      whereas in 8 the vessels were seen beyond the outer suture end without reaching
      host-graft junction (grade I: 1 patient). New vessels usually pointed to the
      outer suture ends of the double-running suture. CONCLUSIONS: Development of
      corneal neovascularization e.g. after keratoplasty can be assessed reliably using
      projected slides of corneal photographs at 100 x magnification. This method has
      the advantage of being more objective, precise and available compared to simple
      evaluation at the slit lamp. Postkeratoplasty corneal neovascularization seems to
      be common in non-high-risk eyes later developing transplant rejection. However,
      new vessels usually do not reach the host-graft junction. Whether
      neovascularization after keratoplasty demonstrates a risk factor for subsequent
      transplant rejection remains to be analyzed in a greater study.

PMID- 11512249
TI  - [Visual rehabilitation and intraocular pressure elevation due to immunological
      graft rejection following penetrating keratoplasty].
AB  - PURPOSE: Endothelial graft rejection and intraocular pressure elevation are the
      most common causes of graft failure following penetrating keratoplasty (PK). Aim
      of this study was to evaluate the visual rehabilitation and the development of
      intraocular pressure during and after graft rejection. PATIENTS AND METHODS: The
      study included 20 eyes of 20 patients (age 54.7 +/- 19.8 years) with endothelial
      graft rejection, that fulfilled the following inclusion criteria 1) graft
      rejection was diagnosed and treated in our department; 2) at least one year
      follow-up after graft rejection; 3) avascular corneal pathology. The mean follow
      up was 23 +/- 14 months. According to the type of surgical procedure patients
      were classified in PK only (n = 15, one after cataract extraction), PK combined
      with extracapsular cataract extraction and intraocular lens (IOL) implantation (n
      = 1); PK combined with secondary IOL-implantation or IOL-exchange (n = 4).
      Standardized complete ophthalmological examinations were performed on a regular
      basis before, during the acute graft rejection und then regularly in a defined
      examination raster in an out-patient service with cornea specialization. RESULTS:
      The time interval between first symptom of 18 acute diffuse and 2 chronic focal
      graft rejection and start of treatment was 9 +/- 13 days. Best-corrected visual
      acuity (CVA) was 0.6 +/- 0.2 before graft rejection and decreased significantly
      at the time of diagnosis (0.2 +/- 0.2; p = 0.001). Six weeks after graft
      rejection CVA was 0.5 +/- 0.2 and remained almost stable until one year after
      rejection (0.6 +/- 0.3) in 16 patients with reversible graft rejection. Only 4
      patients (20%) showed an irreversible graft failure requiring Re-PK. Intraocular
      pressure (IOP) was not elevated in 75% of the patients (n = 15) and did not need
      any antiglaucomatous treatment during and after the rejection phase. In 5 eyes
      (25%) (3 after PK combined with anterior chamber IOL-explantation and secondary
      posterior chamber IOL-implantation; 1 with secondary pseudoexfoliation glaucoma
      and 1 steroidal responder) IOP was elevated during graft rejection (26 +/- 7
      mmHg), but was controlled by intensive topical antiglaucomatous treatment.
      CONCLUSION: Typically, the visual rehabilitation after graft rejection was good
      if the clinical signs were diagnosed just in time and treated adequately. There
      is no direct correlation between graft rejection and intraocular pressure
      elevation. However, the development of intraocular pressure elevation seems to be
      strongly associated with preexisting glaucoma, preexisting anterior synechiae
      and/or simultaneous anterior chamber lens implant removal. A careful patient
      management after PK plays an important role to prevent the development of
      irreversible graft failure due to graft rejection.

PMID- 11512250
TI  - [Effect of pupil size on longitudinal focal distribution after photorefractive
      keratectomy ].
AB  - BACKGROUND: Optical aberrations induced by the transition zone of a myopic
      photorefractive keratectomy (PRK) may degrade the image quality. The subjectively
      evaluated visual acuity and contrast sensitivity may be reduced significantly
      especially with mydriasis. The purpose of this study was to calculate the image
      forming properties of the eye using raytracing techniques of a spot light source
      based on topographic height data of a scanning slit videokeratoscope. METHODS:
      Refractive surfaces were calculated from raw height data sets of the anterior and
      posterior corneal surface measurements (Orbscan, Orbtec, USA). The
      characteristics of the residual refractive surfaces were derived from Navarro's
      eye model. The focal distance was calculated using the exact raytracing
      calculation. Point spread function was determined at the focal plane and at 5
      (delta = 0.2 mm) parafocal planes in front of and behind the focal distance in
      accordance to the pupil diameter (2, 3 and 6 mm). The algorithm was applied to 11
      selected eyes (6 left, 5 right) of 8 patients before and after PRK with myopia (n
      = 6) and myopic astigmatism (n = 5). RESULTS: Before PRK the focal distance did
      not decrease significantly with increasing pupil size (2 to 6 mm), but decreased
      significantly after PRK (-0.41 +/- 0.12 mm, p = 0.02). Preoperatively, the
      variance of the point spread function did not differ significantly between a 2 mm
      (0.046 +/- 0.015 mm) and a 6 mm (0.055 +/- 0.021 mm) pupil size but was affected
      significantly by the pupil size postoperatively (2 mm: 0.049 +/- 0.018 mm, 6 mm:
      0.096 +/- 0.045 mm, p = 0.04). CONCLUSIONS: Raytracing of corneal topography
      height data based on refined eye models with the option of calculation of the
      focus has the potential of tracing the optical resolution of the eye as a
      function of the pupil size. Due to of the altered surface geometry of the cornea
      after myopic PRK, both the variance of the point-spread function and the depth of
      focus increase with pupil size. This may be an explanation for impaired
      subjective refractometry and reduced contrast sensitivity of the patient after
      conventional keratorefractive surgery.

PMID- 11512251
TI  - [Optical coherence tomography in geographic atrophy--a clinicopathologic
      correlation].
AB  - BACKGROUND: Optical coherence tomography was used for the examination of patients
      with geographic atrophy in different stages of age-related macular degeneration.
      Always compared with biomicroscopy and fluorescein angiography [4,7,8,10].
      PATIENTS AND METHODS: 37 patients with geographic atrophy (n = 55 eyes) out of
      150 with AMD (n = 169 eyes) were examined. The results of biomicroscopy,
      fluorescein angiography, optical coherence tomography and histological knowledge
      in age-related macular degeneration were studied. RESULTS: Fluorescein
      angiography always identified geographic atrophy and in 13.5% the findings
      additionally were similar to an occult choroidal neovascularisation with circular
      hyperpigmentation. Geographic atrophy shows a significant thinning of the
      neurosensory retina of 135 microns as an average in optical coherence tomography
      (p < 0.0005) which did not correlate to visual acuity. Typically an enhanced
      vertically sharp demarcated reflectivity of the choroid is found because of the
      lacking pigment epithelium. 43% of the geographic atrophies were identified by
      optical coherence tomography. 3 out of 55 eyes (5%) in optical coherence
      tomography only show macular holes additionally to geographic atrophy.
      CONCLUSION: A typical pattern of reflectivity is found by optical coherence
      tomography with enhanced reflectivity of the choroid because of lacking pigment
      epithelium and significant thinning of the fovea. Atypical macular holes moreover
      are found in 5% neither appearing in biomicroscopy nor in fluorescein
      angiography. An occult choroidal neovascularisation can be differentiated by
      optical coherence tomography from geographic atrophy because there is no spindle
      like thickening of the pigment epithelium and no enhanced choroidal reflectivity.
      In borderline cases optical coherence tomography may be helpful and
      therapeutically decisive in differentiating geographic atrophy and occult
      choroidal neovascularisation and in detecting atypical macular holes.

PMID- 11512253
TI  - [Transplantation of autologous oral mucosa in the treatment of a symblepharon in
      Wegener's disease--a case report].
AB  - BACKGROUND: Wegener's disease, an immune vasculitis, is characterized by
      granulomata and vasculitis of small and large vessels. Ocular manifestations are
      observed in approximately half of all cases. PATIENT: We report on a 58-year-old
      male with severe generalized Wegener's disease which was first diagnosed in 1986.
      The involvement of the central nervous system became clinically manifest by a
      stroke, of the kidneys by incipient renal insufficiency, and of the larynx by
      recurrent subglottic stenosis of the trachea. The first ocular involvement, a
      conjunctivitis, was observed in 1988. Despite systemic immuno-suppressive
      therapy, local conservative therapy and repeated surgical procedures, his vision
      decreased bilaterally from 60/60 to hand movement (OD) and light perception only
      (OS) during the following years because of a massive bilateral symblepharon.
      Transplantation of autologous oral mucosa to the conjunctiva led to a persistent
      increase of vision and a good cosmetic result. CONCLUSIONS: We conclude that in
      patients with Wegener's disease, who have developed a symblepharon despite
      intensive therapy, the transplantation of oral mucosa can produce a sufficient
      functional and cosmetic result.

PMID- 11512252
TI  - [Long-term results after therapy of paraffin induced sclerosing lipogranuloma of
      the eyelids and the anterior orbit in three patients].
AB  - BACKGROUND: Chronic lipogranuloma of anterior orbit and the eyelids is a rare
      inflammatory pseudotumor with a high tendency of recurrence. It is most commonly
      related to prior endonasal sinus surgery. HISTORY AND SIGNS: We report on three
      patients with chronic lipogranulomata who were treated at the university eye
      hospital of Dusseldorf during the last 8 years. These cases are discussed
      individually and longterm results are presented. THERAPY AND OUTCOME: Three
      patients underwent endonasal surgery with postsurgical use of paraffin nasal
      packing prior to the occurrence of chronic lipogranulomata. Histologic findings
      uniformly revealed granulomatous processes but in none was there any sign of a
      systemic granulomatous disorder (such as Boeck's disease). Additionally, one of
      these three patients suffered from neuroophthalmologic impairment due to
      infiltration of oculomotore structures. Early surgical treatment if only for
      extended biopsy did result in immediate severe recurrence of the disease. No
      recurrence of the disease has been observed, however, if surgery was duely
      postponed. CONCLUSIONS: Lipogranulomata seem to be caused by postsurgical
      paraffin nasal packing. Early treatment seems to be unfavourable because of the
      high tendency of recurrence. Surgical removal of any tumor masses should be
      delayed therefore till granuloma formation has presumably come to an end. Any
      early surgery should be limited to a diagnostic biopsy if judged necessary.

PMID- 11512254
TI  - [Massive intraocular invasion of conjunctiva by squamous cell carcinoma--a case
      report].
AB  - BACKGROUND: Squamous cell carcinoma of the conjunctiva is a mostly solitary
      growing tumor located at the limbus region, which seldom invades the eye. We
      present an unusual case of conjunctival carcinoma with marked intraocular
      involvement, which appeared primarily as a chronic inflammation with corneal
      ulcer. CASE REPORT: A 89-year-old female patient was referred to our institution
      with a suspected ulcus rodens of the cornea. Since one year a refractory
      conjunctivitis persisted despite of different local treatment. At first
      presentation, a marked bacterial keratoconjunctivitis with circular necrosis of
      the conjunctiva, corneal infiltration and perforation was seen. Visual acuity of
      the right eye was light perception. The left eye was unremarkable. Enucleation of
      the right eye was performed. Histopathologic examination revealed the diagnosis
      of squamous cell carcinoma of the conjunctiva with intraocular involvement. There
      was a marked infiltration of the choroid even behind the equator. No metastases
      were found. CONCLUSION: Advanced squamous cell carcinoma associated with
      superinfection may present as a primary inflammatory process. There may be
      extensive involvement of the choroid. Metastases are probably rare even in
      advanced cases of this type of carcinoma.

PMID- 11512255
TI  - [When we walk side by side--collaborative action of ophthalmologists and
      employers].

PMID- 11512256
TI  - [Radical cystectomy in superficial bladder carcinoma].

PMID- 11512257
TI  - [Results after treatment with sildenafil citrate in 100 patients with erectile
      dysfunction].
AB  - OBJECTIVE: In order to know the efficiency, tolerance and acceptance of
      Sildenafil Citrate in our area as a new treatment for Erectil Dysfunction (E.D.).
      MATERIAL AND METHODS: We include 100 patients with E.D. who were assisted in our
      medical office from November 1998 to February 2000 to evaluate them according to
      several predeterminated variables. RESULTS: The positive response index (E.D.
      improvement) was 69.9%. We only found side effects in 11.8% (headache 5.4%,
      flushing 4.3%, diarrhea/blurred vision 2.2%). The most widely used dose was 50
      mgrs (65.6%). Only 50.5% of the patients had enough information about Sildenafil.
      The highest positive response index corresponded to the mild E.D. (76.1%). Also
      the best results were achieved with the mixed and psychological etiology (74.1%).
      The Sildenafil treatment was rejected (fear or its price) by the 46.2% of the
      patients. CONCLUSIONS: The Sildenafil Citrate is an effective treatment for the
      E.D. It hardly has any side effects. The 50 mgrs dose got the best results.
      Almost half of the patients complained about an insufficient information on this
      pharmaceutical. Sildenafil got a good response even when there were risk
      associated factors of E.D.

PMID- 11512258
TI  - [Epidemiology of urinary lithiasis].
AB  - An epidemiological study of urinary stone disease has been carried out in the
      districts of La Sierra and Hellin (Albacete, Spain). Between January 1992 and
      December 1999 a total of 887 patients with urinary lithiasis have been studied,
      analysing the number of patients discharged from hospital with the primary
      diagnosis of lithiasis, the distribution of lithiasis by area, age, gender,
      family history of lithiasis, diet, occupation and concurrent pathology. The
      geographical, geological, and climatic conditions, the composition of the water
      supply and the clinical characteristics are described. The incidence of urinary
      lithiasis in the whole area in 2.66 per thousand inhabitants/year, showing a male
      predominance with a male:female ratio of 1.26:1. The mean age was 51.34 years
      (bimodal distribution with peaks in the 4th and 7th decades). 20.41% of the
      patients had a family history, with the father being the most frequently affected
      relation. Those occupations associated with a sedentary life style or with a hot,
      dry workplace show a higher incidence of lithiasis. A hot, dry climate favours
      the formation of urinary lithiasis and the highest incidence of lithiasis is in
      the summer, during the months of July and August. No statistically significant
      influence was shown between at the hardness of the water and the incidence of
      urinary lithiasis in the study population.

PMID- 11512259
TI  - [Factors affecting the PSA:alpha 1 antichymotrypsin/total PSA ratio].
AB  - OBJECTIVES: To evaluate the influence of several factors, including age, prostate
      volume, total PSA (PSA-T), clinical stage and Gleason on the PSA:alpha 1ACT/PSA-T
      (C/T) ratio. MATERIAL AND METHODS: Using in-house assays, we measured plasma
      levels of PSA-T and PSA:alpha 1ACT complex in 622 patients with benign prostate
      hyperplasia (BPH) (455 with hystological confirmation and 167 with clinical
      evidence of absence of malignance) and in 255 patients with prostate cancer
      (CaP), and determined the correlation between different parameters. RESULTS: In
      BPH patients, PSA-T and PSA:alpha 1ACT significantly increased with age. There
      was a positive correlation between age and PSA-T (r = 0.161, p < 0.0001) and
      PSA:alpha 1ACT (r = 0.141, p = 0.001). In contrast, the C/T ratio remained
      constant and below 70% in all decades. Similar results were obtained in CaP
      patients. In BPH patients, there was a positive correlation between prostate
      volume and PSA-T and PSA:alpha 1ACT, but not with the C/T ratio. In CaP patients,
      however, there was a negative correlation between prostate volume and the C/T
      ratio. An excellent correlation was found between PSA-T and PSA:alpha 1ACT, and a
      good correlation between PSA-T and the C/T ratio and between PSA:alpha 1ACT and
      C/T ratio. A multiple regression analysis showed that, in HBP and CaP patients,
      PSA-T and PSA:alpha 1ACT complex were the only parameters that significantly and
      independently influenced the C/T ratio. CONCLUSIONS: The C/T ratio is independent
      of age, prostate volume, Gleason and clinical stage. Therefore, these factors
      need not to be considered when using the C/T ratio.

PMID- 11512260
TI  - [Incidence and treatment of urinary lithiasis in renal transplantation].
AB  - INTRODUCTION: Urinary calculi is an uncommon complication in kidney
      transplantation; several stone risk factors are found in transplanted patients,
      but in most cases there is not a relationship between these risk factors and
      stone formation. The treatment of these patients is complex due to their both
      immunosuppressive status and border-line renal function. MATERIAL AND METHOD:
      From 1980 to February 2000, 1198 kidney transplant have been performed in our
      institution. We describe our series consisting in 22 urinary calculi (15 in the
      graft, 3 in the urether and 4 in the bladder) in 18 patients, including 7 stones
      detected in cadaveric donor patients. RESULTS: We performed external shock wave
      lithotripsy in 7 patients, bench surgery in 4, endoscopic mechanic lithotripsy in
      5, open surgery in 1 and observation in 6. Calcium oxalate (mono and dihidrate)
      was found in 9 of 13 calculi. Metabolic changes were found in 15 of the 18
      patients, the most common was hiperuricemia. There were not complications of
      every treatment applied and 9% of them needed a savage treatment. We found
      recurrence in 4 cases (22.2%). Now 12 of the patients are stone-free (66.7%) and
      three have non-significative stones (83.3% without symptoms). CONCLUSIONS:
      Detection of renal calculi in cadaveric renal donors is not a reason to refuse
      the graft for further transplantation. In both renal calculi up to 2 cm and
      uretheric calculi surgical treatment is assessed as first option. In caliceal
      stones smaller than 5 mm observations is the best treatment.

PMID- 11512261
TI  - [Treatment of stenosis in uretero-intestinal anastomosis].
AB  - We report our experience in the treatment of uretero-enteric anastomotic
      strictures. Our incidence in this complication is 3.8% in orthotopic bladder
      substitution and 8.3% in ileal conduict. MATERIAL AND METHODS: We have treated
      this complication in 6 patients with orthotopic bladder substitution and 4 with
      ileal conduict. We tried to perform a dilatation with a high pressure balloon and
      to place a Double-J catheter. RESULTS: In 4 cases we could not introduce the
      guidewire through the stricture because there was a total stop. In the others 6
      cases, one is doing well without Double-J, another one did not tolerate the
      catheter and we performed an open surgical reanastomosis, 2 kept the catheters
      until their death due to metastases and the other two continue alive with their
      catheter periodically replaced. CONCLUSIONS: The direct uretero-enteric
      anastomoses present less stenoses risk. Endourological techniques should be the
      first option in treatment of these patients.

PMID- 11512262
TI  - [Leydig cell tumor. Report of 2 cases and review of the literature].
AB  - The Leydig cell tumor is the most frequent of non-germ cell tumors of the testis.
      Clinical findings depend on the age of presentation. We present two cases of
      Leydig Cell tumors of the testis, diagnosed in a 8 years old child with isosexual
      precocity, and a 42 years old adult with Gynaecomastia. After reviewing the
      existing literature on this uncommon pathology we consider that the iconography
      presented is very interesting for furthering the knowledge on this subject.

PMID- 11512263
TI  - [Fibroepithelial polyp of the urethra in a young woman].
AB  - OBJECTIVE: We present the case of a fibroepithelial polyp from the uretra of a
      young female, analysing the factors that make this an interesting case. MATERIAL
      AND METHODS: A case-report of a fibrous polyp from the urethra of a young female,
      an analysis of its differential diagnosis and a review of the literature. RESULTS
      AND CONCLUSIONS: The fibrous polyp of the urethra (fibroepithelual polyp, simple
      polyp, pedunculated polyp) is a rare benign epithelial tumour, more frequently
      encountered in males and in the posterior urethra. When it appears in females it
      is usually located in the external meatus and normally asymptomatic, although it
      can also present with a mictional syndrome, terminal hematuria or urethral
      hemorrhage. The differential diagnosis includes other benign epithelial tumours
      of the urethra, such as the caruncula, mainly the granulomatous, very difficult
      to differentiate, the squamous papilloma and the acuminated chondiloma. A
      clinical examination and histological study are necessary for a correct
      diagnosis, and treatment consists of surgical resection.

PMID- 11512264
TI  - [Transitional carcinoma of the ureter and ipsilateral synchronous renal cell
      carcinoma in hydronephrotic atrophic kidney: infrequent association].
AB  - We report a new case of simultaneous occurrence of renal cell carcinoma and
      transitional cell carcinoma into ipsilateral ureter. A review of the literature
      to date indicates this is the 45 world-wide case and the 8 in the Spanish
      publications.

PMID- 11512266
TI  - [Treatment of ureteral stenosis with vermiform appendix].
AB  - Contribution of one case of iatrogenic ureteral stenosis, successfully managed in
      a single-kidney patient by substitution with a vermiform appendage. Description
      of the technique used and brief review of open surgery techniques used in repair
      of ureteral defects. After a two-year follow-up, the correct functioning of the
      appendicular graft with preserved renal morphological function is confirmed.
      Ureteral substitution with an appendage is a good indication for extensive
      ureteral defects with right mid-ureter location.

PMID- 11512265
TI  - [Leiomyosarcoma of the urinary bladder].
AB  - We report a case of bladder leiomyosarcoma treated at our department. We review
      the published papers about this entity. We emphasize the low incidence of that
      pathology and the lack of consensus about treatment.

PMID- 11512267
TI  - [Sugar: treatment of choice in irreducible paraphimosis].
AB  - PURPOSE: To evaluate the effectivity of granulated sugar in the treatment of
      irreductable paraphimosis. CLINICAL CASES: During last year three patients have
      been treated by application of granulated sugar on prepuce and glands penis
      during 1-2 hours until edema reduction was observed. Paraphimosis could be
      reducted in all three cases. CONCLUSIONS: Sugar application reduce local edema
      permitting reduce paraphimosis in an incruent, cheap and without side effects
      way.

PMID- 11512268
TI  - [Renal abscess in patients with HIV infection in the era of highly active
      antiretroviral therapy].
AB  - Renal abscess is a very rare complication of HIV infection, usually occurs in
      patients with severe immune deficiency. The immune status is the main factor that
      predict disease advancement. Highly activate antiretroviral therapy (HAART)
      improve the CD4 cell count. We present a case of renal abscess for Aspergillus
      niger in a HIV+ patient who complained of right flank mass and fever. We review
      relevant literature and the management of these patients.

PMID- 11512269
TI  - [Hypercalcemia, leukemoid reaction, and thrombocytosis as paraneoplastic
      presentation of transitional cell carcinoma of the kidney].
AB  - The most common etiologies of hypercalcemia are hyperparathyroidism or
      malignancy, most often of the lung, breast or hematological system, but rarely
      occur in transitional cell carcinoma. The appearance of this metabolic disorder
      and other paraneoplastic signs like leukemoid reaction or thrombocytosis is a
      potential marker for malignant behaviour and poor prognosis in advanced tumours.
      Simultaneous presentation of that three paraneoplastic signs have only been
      described in two patients with wellknown bladder carcinoma. Most paraneoplastic
      syndromes appear only during the late stages of malignancy when the diagnosis has
      long been established, but sometimes may be an early sign of the malignancy. We
      describe a case of a previously unknown infiltrating transitional cell carcinoma
      of the kidney without bony metastasis, that presented itself with hypercalcemia,
      hyperleukocytosis resembling a leukemoid reaction and thrombocytosis. We think
      recognizing the paraneoplastic syndrome is very important because it is an alarm
      sign of malignancy.

PMID- 11512270
TI  - [Spanish Journal of Urology (founded in 1977 as Actas Urologicas Espanolas].

PMID- 11512271
TI  - Synthesis and antiproliferative activity in vitro of new derivatives of 3
      aminopyrazolo[3,4-b]pyridine. Part 1. Reaction of 3-aminopyrazolo[3,4-b]pyridine
      with 1,3-, 1,4-diketones and alpha,beta-unsaturated ketones.
AB  - The synthesis of several new pyrazolo[3,4-b]pyridine, pyrido[2',3':3,4]
      pyrazolo[1,5-a]pyrimidine and imidazo[1',2':1,5]pyrazolo[3,4-b]pyridine
      derivatives is described. The obtained compounds were tested for their
      antiproliferative activity in vitro. One of them, 4-phenyl-2-(3,4,5-trimethoxy
      beta-styrylo)pyrido- [2',3':3,4]pyrazolo[1,5-a]pyrimidine (9), revealed cytotoxic
      properties against the cells of all three human cancer cell lines applied.
      Another one, 2,4-dimethyl-pyrido[2',3':3,4]pyrazolo[1,5-a]-pyrimidine (2),
      revealed weak cytotoxic activity only against the cells of human bladder cancer
      cell line HCV29T. All other compounds tested did not reveal any cytotoxic
      activity.

PMID- 11512272
TI  - Synthesis of 3-nitrosoimidazo[1,2-a]pyridine derivatives as potential
      antiretroviral agents.
AB  - Ten 2-aryl or heteroaryl-3-nitrosoimidazo[1,2-a]pyridine derivatives were
      synthesised as potential antiretroviral agents. The new compounds were
      characterized by elemental analysis, 1H NMR, and by crystallography for (14). The
      compounds were devoid of any activity against HIV-1 or HIV-2.

PMID- 11512273
TI  - Targeting of human Tmolt4 leukemic type II IMP dehydrogenase by cyclic imide
      related derivatives.
AB  - 2,3-Dihydrophthalazine-1,4-diones, indazolones, 3-imino-1-oxoisodolines,
      homophthalimides, napthalidimides, diphenamides, and 6,7-dihydro-5H
      dibenz[c,e]azepines proved to be potent inhibitors of the activity of human
      Tmolt4 T cell leukemia Type II IMP dehydrogenase (IMPDH). This inhibition was
      competitive, yielding Ki values in the range of 1.96 to 48.9 microM. The
      inhibition of Type II IMPDH correlated positively with the inhibition of the
      growth of Tmolt4 cells, the syntheses of DNA and purine, and the activity of
      crude IMPDH. The Type II IMPDH isoform is found in rapidly proliferating cells.
      The isoform present in normal resting cells, Type I IMPDH, was elevated by the
      compounds at 100 microM. In addition, Compound 5 significantly increased the Type
      I enzyme activity in a concentration and time dependent manner. The selectivity
      of these derivatives towards Type II IMPDH will allow for the separation of
      cellular effects, which should reduce clinical toxicity when treating with
      antimetabolite IMPDH inhibitors.

PMID- 11512274
TI  - Aromatic extended bisamidines: synthesis, inhibition of topoisomerases, and
      anticancer cytotoxicity in vitro.
AB  - A series of four aromatic extended bisamidines (12-15) differing in the nature of
      their terminal basic side chains were synthesized and evaluated for cytotoxic
      activity in MCF-7 cultured breast cancer cells. The concentrations of 12, 13, 14,
      and 15 needed to inhibit [3H]thymidine incorporation into DNA by 50% (IC50) were
      found to be 63 microM, 85 microM, 77 microM, and 97 microM, respectively. To test
      whether cytotoxic properties were related to DNA-binding and topoisomerase
      action, the bisamidines 12-15 were evaluated in a cell-free system. Data from the
      ethidium displacement assay showed that bisamidines 12-15 have significant
      affinity for DNA and show moderate specificity for AT base pairs. In the
      topoisomerase II assay, the relaxation of DNA was inhibited with all four drugs
      and the extent of inhibition was directly proportional to the drug concentration.
      This suggests that DNA binding may be implicated in the cytotoxicity of these
      bisamidines, possibly by inhibiting interactions between topoisomerase II and
      their DNA targets.

PMID- 11512275
TI  - Synthesis and 5-HT2A antagonist activity of derivatives of the novel heterocycles
      indolo[3,2-d]pyrrolo[3,2-g]azecine and benzo[d]pyrrolo[3,2-g]azecine compared to
      the benz[d]indolo[2,3-g]azecine derivative LE 300.
AB  - An indolo[3,2-d]pyrrolo[3,2-g]azecine and a benzo[d]pyrrolo[3,2-g]azecine
      analogue of the potent dopamine receptor antagonist LE 300 (7-methyl
      6,7,8,9,14,15-hexahydro-5H-benz[d]indolo[2,3-g]azecine) have been prepared in
      multi-step reactions via C-N bond cleavage of corresponding quaternary N
      methylquinolizinium iodides. LE 300, the target compounds and two precursor
      quinolizines have been tested in vitro for antagonist activity at 5-HT2A
      receptors (rat tail artery) and H1 receptors (guinea-pig ileum), respectively. LE
      300 and compound 19 (3,6-dimethyl-4,5,6,7,8,13-hexahydro-3H-benzo[d]pyrrolo[3,2
      g]azecine) competitively inhibited 5-HT-induced contractions with similar
      nanomolar potency (pA2 = 8.32 and 8.01, respectively) but were less active than
      the reference antagonist ketanserin (pA2 = 9.55). Compound 19 displayed moderate
      H1-antihistaminic activity in the guinea-pig ileum assay (pA2 = 7.37).

PMID- 11512276
TI  - Improvement and validation of the fluorescence-based histone deacetylase assay
      using an internal standard.
AB  - The determination of the activity of histone deacetylase (HDAC) and the potency
      of its inhibitors has become an important goal in medicinal chemistry. This is
      due both to the involvement of HDAC in gene regulation and the ability of its
      inhibitors to modulate transcription and induce differentiation and/or apoptosis
      in cancer cells. We have previously reported the development of a non-isotopic
      assay for HDAC using a fluorescent derivative of epsilon-acetyl lysine. It can
      replace existing methods that rely on radioactively labeled histones or
      oligopeptides as substrates. Here we report validation and improvement of the
      procedure using an internal standard for the quantitation of the fluorescent
      substrate by HPLC.

PMID- 11512277
TI  - A simple procedure for synthesis of roxindole, a dopamine D2-receptor agonist.
AB  - A modified convenient and high yielding synthetic route for the preparation of
      the dopamine agonist roxindole 1 is described. The key step in our method is the
      phase-transfer catalyzed reaction of gamma-butyrolactone with 5-methoxyindole
      which results in the indolylbutyric acid derivative directly in one step.

PMID- 11512278
TI  - Two sulfonamides-containing dihydropyrone derivatives as HIV protease inhibitors.

PMID- 11512279
TI  - A comparative study of the enantiomeric resolution of several tetralone
      derivatives on macrocyclic antibiotic chiral stationary phases using HPLC under
      normal phase mode.
AB  - The enantiomeric resolution of five substituted 2-(4-pyridylalkyl)-1-tetralone
      derivatives has been achieved on three macrocyclic glycopeptide antibiotic chiral
      stationary phases namely, Chirobiotic R, T, and V columns. The mobile phase used
      was hexane-ethanol-triethylamine (12:8:0.01, v/v/v). The flow rates were 1 mL/min
      for Chirobiotic T and 2 mL/min for Chirobiotic R and V respectively. The UV
      detection was carried out at 254 nm. The values of alpha of the resolved
      enantiomers of the reported tetralone derivatives were in the range of 1.32 to
      2.51 on Chirobiotic R, 2.02 to 2.88 on Chirobiotic T and 1.55 to 2.54 on
      Chirobiotic V respectively while the values of Rs were in the range of 1.00 to
      2.50 on Chirobiotic R, 1.00 to 1.95 on Chirobiotic T and 1.00 to 1.60 on
      Chirobiotic V respectively. The best resolution was achieved on Chirobiotic R
      column.

PMID- 11512280
TI  - [Respiratory filters and pneumonia: many unresolved questions].
AB  - BACKGROUND AND OBJECTIVE: The use of heat and moisture exchanging filters (HMEF)
      instead of conventional heated humidifiers is a cost-effective method in
      intensive care medicine. It was the objective of this paper to investigate the
      evidence for HMEF from the viewpoint of prevention of pneumonia and to
      investigate the appropriate changing intervals as well as filter materials.
      METHOD: Randomised controlled trials published in recent years and focusing on
      prevention of pneumonia as well as other prospective controlled studies were
      reviewed systematically. RESULTS: The studies demonstrate neither a clear
      advantage nor disadvantage of HMEF. No final statement is possible concerning
      changing intervals and the most appropriate filter materials. However, the data
      give some evidence for a possible extension of changing intervals to 72 hours
      without harm to the patients and probably show very little influence of filter
      materials. CONCLUSION: Because of the economic advantages of HMEF instead of an
      active humidification, the use of filters--with the exception of
      contraindications for individual patients--should be preferred.

PMID- 11512281
TI  - [Genotoxic effect of the insecticides pentachlorophenol and lindane on human
      nasal mucosal epithelium].
AB  - BACKGROUND AND OBJECTIVE: In numerous experimental and epidemiologic studies
      Pentachlorphenol (PCP) and Hexachlorcyclohexan (Lindane) have been shown to be of
      potential carcinogenic risk for human epithelial cells. In the past, these two
      substances have been used for both, military and non-military purposes, e.g. for
      impregnation of textiles and uniforms. In this study we investigated the
      genotoxic effect of PCP and Lindane on human mucosal tissue from the middle and
      lower nasal turbinate. METHODS: In biopsy samples obtained from nasal epithelia
      during surgery cell vitality was evaluated by trypan-blue-staining. The specimens
      were incubated for 60 minutes with PCP (0.3; 0.75 und 1.2 mumol/l) and Lindane
      (0.5; 0.75; and 1.0 mumol/ml). The induction of DNA-damage (single-strand-breaks
      and double-strand-breaks) caused by PCP and Lindane was measured using single
      cell microgel electrophoresis. Evaluation was performed by fluorescence
      microscopy. RESULTS: Especially in mucosa cells from the middle turbinate severe
      DNA-damages were recognized after exposition to PCP and Lindane proposing a
      strong genotoxic effect. In cells from the lower turbinate DNA-changes caused by
      PCP and Lindane were significantly lower. However a considerable genotoxic effect
      was also present. CONCLUSION: This study shows for the first time that there are
      clear facts indicating mutagenic effects of PCP and Lindane on nasal epithelia.
      Furthermore, this is the first study showing different susceptibility of two
      anatomic subsites in the nose for different pesticides. Concerning the biological
      plausibility, this study offers important arguments for evaluating the role of
      PCP and Lindane in the induction of upper aerodigestive tract cancer.

PMID- 11512282
TI  - [Circumscribed hypertrichosis lanuginosa in acute myeloid leukemia].
AB  - HISTORY AND CLINICAL FINDINGS: The case of a 70 year old male is presented. Past
      medical history revealed the following diagnoses: liver cirrhosis, splenomegaly,
      thrombocytopenia, macrocytic anaemia, chronic obstructive pulmonary disease, type
      IIa diabetes mellitus and peripheral vascular disease of the lower limbs with
      chronic leg ulcers. Within 6 weeks the patient developed an increasing number of
      pigmented lanugo type hair over both cheeks, zygomatic arches and temples. The
      diagnosis of circumscribed acquired hypertrichosis lanuginosa (AHL) was
      established. Bone marrow biopsy revealed presence of acute myeloid leukemia.
      THERAPY AND CLINICAL COURSE: Chemotherapy with hydroxycarbamide (Syrea) was
      started without effect on haematologic parameters. The patient was transferred to
      the oncology unit where he died soon afterwards. CONCLUSION: Acquired
      hypertrichosis lanuginosa (AHL) is a paraneoplastic syndrome. It is mainly
      associated with adenocarcinoma of lung and bowel, however other histologic types
      of tumours and localisations have been described. About 50 cases have been
      reported in the literature until 1998. To our knowledge this is the first case of
      AHL described in association with acute myeloid leukemia.

PMID- 11512283
TI  - [Intrapulmonary tumor cell embolism from cancer of the bladder as the cause of a
      subacute cor pulmonale].
AB  - HISTORY AND CLINICAL FINDINGS: A 61-year-old man had over 3 weeks experienced
      increasing dyspnoea on effort and loss of appetite. He reported previous chronic
      pain with a "stiffened hip" treated long-term with diclofenac, and three
      transurethral surgical interventions. It was only at the latest admission that
      bladder cancer (first diagnosed 2 years previously) became known as the reason
      for the interventions. On admission pallor, sinus tachycardia, fever of 38
      degrees C and dyspnoea on light exertion were noted, but blood pressure was
      normal. INVESTIGATIONS: Chest X-ray was normal, but the patient had marked
      respiratory insufficiency (pO2 30.8 mmHg, pCO2 31.6 mmHg) on room air.
      Echocardiography showed a dilated right ventricle with paradoxical septal
      movement. There was no evidence of thrombosis in the leg veins on ultrasound. D
      dimers were normal. DIAGNOSIS, TREATMENT AND COURSE: Pulmonary artery embolism of
      unknown origin was suspected. Despite anticoagulation with low-molecular heparin
      the patient's condition deteriorated. Spiral computed tomography of the thorax
      did not show thrombi in the pulmonary arterial vessels. Perfusion scintigraphy
      demonstrated definite perfusion deficits bilaterally in the upper lobes of the
      lung, consistent with pulmonary embolism. As his condition gradually worsened rt
      PA was started to achieve fibrinolysis, but failed to produce any change in
      haemodynamic and respiratory functions. He died a few hours later. Microscopic
      examination at autopsy revealed multiple tumour emboli with intimal fibrosis in
      the peripheral arteries. A poorly differentiated urothelial carcinoma of the
      bladder with extensive infiltration of blood vessels was found (carcinomatous
      haemangiosis). CONCLUSION: A malignant tumour with micro-embolization of tumour
      cells should be considered as a possible diagnosis when the clinical picture
      indicates pulmonary embolism of unknown genesis.

PMID- 11512284
TI  - [Monoclonal antibody therapy].

PMID- 11512285
TI  - [Diagnosis of pulmonary arterial embolism].

PMID- 11512286
TI  - [Amyotrophic lateral sclerosis].

PMID- 11512287
TI  - [Amaurosis fugax].

PMID- 11512288
TI  - [Treatment of risk factors in primary prevention of cerebral ischemia].

PMID- 11512289
TI  - [Infection thesis as explanation of the higher incidence of myocardial infarction
      in males].

PMID- 11512290
TI  - The International Society of Radiology.

PMID- 11512292
TI  - Bilateral primary adrenocortical carcinoma complicated by Addisonian crisis: case
      report.

PMID- 11512293
TI  - Diagnostic accuracy of a stereotaxically guided vacuum-assisted large-core breast
      biopsy program in Canada.
AB  - OBJECTIVE: To assess the accuracy rate associated with 11-gauge vacuum assisted
      large-core breast biopsy (VALCBB) at our institution. METHODS: 673 consecutive
      VALCBBs performed between September 1997 and March 2000 were evaluated. For most
      of the benign VALCBB specimens, accuracy was determined by the stability of the
      lesions on follow-up mammography. When possible, histological results of
      specimens obtained from VALCBB and of specimens obtained from surgical excision
      were compared. Modified accuracy rates were calculated. RESULTS: Of the 673
      biopsies, 499 (74%) were benign; for the 315 benign lesions for which complete
      follow-up information was available, a greater than 99% modified accuracy rate
      was obtained. The modified accuracy rate for the 174 nonbenign lesions was 95%.
      Thus, VALCBB yielded an overall modified accuracy for both benign and nonbenign
      lesions of 97.9%. CONCLUSION: VALCBB provides accurate histological results for
      biopsy of suspicious lesions of the breast.

PMID- 11512294
TI  - High-output cardiac failure secondary to multiple vascular malformations in the
      liver: case report.

PMID- 11512295
TI  - Use of heparin in the investigation of obscure gastrointestinal bleeding.
AB  - OBJECTIVE: To determine if the administration of heparin improves the predictive
      value of angiography in the investigation of obscure gastrointestinal (GI)
      bleeding. METHODS: 18 patients with a history of chronic GI bleeding were
      investigated with angiography. For 6 patients, the cause of GI bleeding was
      established with angiography; the 12 patients who had negative results were given
      heparin for 24 h and were reassessed with angiography. RESULTS: After heparin
      administration, the source of GI bleeding was determined with angiography for 6
      of the remaining 12 patients. Thus, heparinization increased diagnostic yield
      from 33% (6 of 18) to 67% (12 of 18). No significant complications, such as
      uncontrolled GI bleeding, occurred. CONCLUSION: Heparinization improves the
      diagnostic yield of angiography when obscure GI bleeding is being investigated.

PMID- 11512296
TI  - Rotational changes in the morphology of the vertebral artery at a common site of
      artery dissection.
AB  - OBJECTIVE: Given that vertebral artery dissection and transient vertebrobasilar
      insufficiency occurs commonly at the C1-C2 junction, the objective was to study,
      in vivo, the normal rotational anatomy at C1-C2 using magnetic resonance
      angiography (MRA) with 3-dimensional (3D) reconstructions and to correlate these
      reconstructions with our experience of dissection location. METHODS: 3D phase
      contrast MRAs were obtained from the foramen magnum to C3 in 4 normal volunteers
      in neutral and rotated (45 degrees) positions. The magnitude images were used as
      source images for 3D reconstruction. The images from only 1 of the volunteers
      were completely motion free, and these were subjected to arterial length
      calculations using image analysis wire frame outline of the vessel. All
      angiograms of vertebral artery dissection obtained at our institution from 1993
      to 1997 were also reviewed. RESULTS: 3D reconstructions document elongation
      (approximately 7% in quantitatively analyzed case) and slight narrowing of the
      artery contralateral to the direction of head rotation from C2 to the dural entry
      point. The artery turns most sharply and is subject to the anterior force of the
      rotating C1 vertebra as it exits the C1 foramen. Of 14 cases of vertebral artery
      dissection, 50% occurred between the transverse foramen and the posterior lamina
      of C1. CONCLUSIONS: With head rotation, the contralateral vertebral artery
      undergoes the greatest anatomical distortion as it exits the C1 transverse
      foramen. This increased stress may account for the higher frequency of
      dissections at this location.

PMID- 11512297
TI  - Peripheral vascular malformations: diagnosis and percutaneous management.
AB  - Vascular malformations are complex lesions, and their management presents a
      challenging set of problems. Because VMs are usually treated electively, referral
      to a centre with a multidisciplinary team approach and with experience diagnosing
      and treating VMs is recommended. The cornerstone of therapy, embolization,
      provides both the opportunity for interventional radiologists to become involved
      in primary patient care and unique challenges that are traditionally not the
      purview of radiologists.

PMID- 11512298
TI  - Ultrasonographic features of an adductor longus tear: case report.

PMID- 11512299
TI  - Radiologic diagnosis of bone tumours using Webonex, a Web-based artificial
      intelligence program.

PMID- 11512300
TI  - Visual and semiquantitative analysis of 18F-fluorodeoxyglucose positron emission
      tomography using a partial-ring tomograph without attenuation correction to
      differentiate benign and malignant pulmonary nodules.
AB  - OBJECTIVE: Many studies have reported the use of attenuation-corrected positron
      emission tomography with 18F-fluorodeoxyglucose (FDG PET) with full-ring
      tomographs to differentiate between benign and malignant pulmonary nodules. We
      sought to evaluate FDG PET using a partial-ring tomograph without attenuation
      correction. METHODS: A retrospective review of PET images from 77 patients (range
      38-84 years of age) with proven benign or malignant pulmonary nodules was
      undertaken. All images were obtained using a Siemens/CTI ECAT ART tomograph,
      without attenuation correction, after 185 MBq 18F-FDG was injected. Images were
      visually graded on a 5-point scale from "definitely malignant" to "definitely
      benign," and lesion-to-background (LB) ratios were calculated using region of
      interest analysis. Visual and semiquantitative analyses were compared using
      receiver operating characteristic analysis. RESULTS: Twenty lesions were benign
      and 57 were malignant. The mean LB ratio for benign lesions was 1.5 (range 1.0
      5.7) and for malignant lesions 5.7 (range 1.2-14.1) (p < 0.001). The area under
      the ROC curve for LB ratio analysis was 0.95, and for visual analysis 0.91 (p =
      0.39). The optimal cut-off ratio with LB ratio analysis was 1.8, giving a
      sensitivity of 95% and a specificity of 85%. For lesions thought to be
      "definitely malignant" on visual analysis, the sensitivity was 93% and the
      specificity 85%. Three proven infective lesions were rated as malignant by both
      techniques (LB ratio 2.6-5.7). CONCLUSIONS: FDG PET without attenuation
      correction is accurate for differentiating between benign and malignant lung
      nodules. Results using simple LB ratios without attenuation correction compare
      favourably with the published sensitivity and specificity for standard uptake
      ratios. Visual analysis is equally accurate.

PMID- 11512301
TI  - Role of transrectal ultrasonography in evaluating the cause of azoospermia.
AB  - OBJECTIVE: To assess the role of transrectal ultrasonography in the investigation
      of azoospermia, a significant cause of infertility. METHODS: Over a 2-year
      period, 35 patients with azoospermia underwent an infertility workup, which
      included transrectal ultrasonography. RESULTS: Sonograms of 10 of the 35 patients
      were normal; 8 patients had enlarged seminal vesicles containing cysts, 6 had
      ejaculatory duct dilation, 5 had seminal vesicle calcification, 3 had seminal
      vesicle atrophy-hypoplasia and 3 patients had midline prostatic cysts.
      CONCLUSION: Transrectal sonography is a useful modality to evaluate seminal duct
      abnormalities, some of which may cause azoospermia.

PMID- 11512302
TI  - Residents' corner. Answer to case of the month #83. Askin tumour of the chest
      wall.

PMID- 11512303
TI  - The UNOS Scientific Renal Transplant Registry--2000.
AB  - During the 46 years since the first successful kidney was performed, more than
      200,000 kidney transplants at United States transplant centers have been reported
      to the UCLA and UNOS Transplant Registries. After more than 25 years of follow
      up, only 4% of cadaver donor transplants and 22% of living donor transplants
      performed before 1975 are still functioning. When compared with the 30% and 58% 5
      year cadaveric and living donor graft survival rates, respectively, reported for
      kidney transplants 25 years ago, today's results of 66% and 78% are remarkably
      improved. Between 1995-1999, the 5-year graft survival rates for living donor
      transplant recipients were 80% for whites, 64% for American blacks and 84% for
      Asians and others. Among recipients of cadaver kidneys the results for the same
      racial groups were 70%, 55% and 76%, respectively. HLA-identical sibling
      transplants provided the best results in whites and blacks with 5-year graft
      survival rates of 90% and 88% respectively, and superior graft half-lives of 42
      and 27 years. No substantial survival differences were noted among whites who
      received an HLA-mismatched living donor graft (5-year graft survival ranged from
      76-81%). Among blacks who received HLA-mismatched living donor kidneys, 69% of
      sibling grafts survived 5 years compared with 60-62% of all others (p = 0.035).
      The racial distribution at the 25 largest US transplant centers varied from 6-64%
      black recipients. Graft survival rates for both blacks and whites were comparable
      at centers that transplanted more than 33% blacks or less than 20% blacks,
      suggesting that a larger experience with minority patients does not confer an
      advantage manifested in graft survival. Blacks consistently had higher rates of
      early rejection (34% vs. 28% in the first year) and delayed graft function (31%
      vs. 23%) than whites. Rejection prior to discharge resulted in a decreased one
      year graft survival rate from 89% to 76% for both racial groups. DGF also reduced
      one-year graft survival from 82% to 76% for both racial groups. However, long
      term graft survival rates were 15% lower for blacks than whites when there was no
      rejection or when there was no DGF. Sensitization patterns were similar comparing
      blacks and whites stratified according to sex, pregnancies, pretransplant
      transfusions, and previous transplants. There was no indication among patients
      transplanted between 1995-1999 for higher rates of sensitization among blacks.
      Recipients over age 60 had the lowest graft survival rate among whites (60% vs.
      71% for those aged 19-45; p < 0.001). Among blacks, older recipients had the
      highest graft survival rate (57% vs. 55% for those aged 19-45; p = ns). Blacks
      aged 6-18 had the poorest 5-year survival rate (44%). The donor's age was an
      important determinant of long-term survival in both whites and blacks. The 5-year
      graft survival rates fell from 74-57% when the donor age was over 60 among
      whites. However, the difference was more pronounced among blacks, with a 5-year
      survival rate of 64% when the donor was aged 19-30, 47% when the donor was aged
      46-60 and 35% when the donor was over 60 (p < 0.001). Increasing numbers of HLA
      mismatches resulted in a significantly increased incidence of rejection episodes
      in both blacks and whites. More than 19% of whites received an HLA-matched graft
      during 1995-1999 compared with 6% of blacks. HLA matching improved 3-year graft
      survival by 7-8% for both whites and blacks. Causes of graft failure were similar
      for blacks and whites during the first posttransplant year, however, after one
      year, blacks were more likely than whites to have an immunological graft loss
      whereas whites more often died with a functioning graft. The causes of patient
      death were also similar between blacks and whites during the first year, but
      after one year, blacks were more likely than whites to die from infection whereas
      whites more often died from cardiovascular disease and from malignancies. The
      racial disparity in renal allograft survival rates has diminished. The graft
      survival difference between whites and blacks at one year is now less than 2%.
      The long-term survival rates have also improved for blacks but the rate of late
      graft loss remains nearly double that for whites.

PMID- 11512304
TI  - Renal transplantation in the UK and Republic of Ireland.
AB  - RENAL TRANSPLANT OUTCOME: Analysis of 5-year transplant survival in the UK showed
      a number of significant factors influencing outcome of adult cadaveric renal
      transplantation. Data from 5,963 first grafts and 1,078 regrafts carried out
      between 1990-1997 showed year of graft, recipient age and diabetes, donor age,
      kidney exchange between centres and HLA matching to influence 5-year outcome. The
      most important prognostic factor was donor age: the risk of transplant failure
      within 5 years for grafts using kidneys from donors aged 60 years and over was
      double that of grafts using donors aged 18-34 years. Unlike the effect of donor
      age, the influence of HLA matching would appear to be diminishing with time. In
      contrast to transplants in the 1980's, the difference in 5-year transplant
      survival between 000 mismatched and favourably matched (100, 010 or 110
      mismatched) transplants is no longer significant. An analysis of posttransplant
      survival for first grafts in different epochs (0-3 months, 3 months to 3 years
      and beyond 3 years) showed that one factor affected short-term outcome (exchange
      of kidneys between centres), whereas others affected outcome throughout the
      epochs (most notably donor age, recipient age and recipient diabetes). RECIPIENT
      AND DONOR AGE MATCHING: The mean recipient age in the UK and Republic of Ireland
      increased by 5 years between 1981-1990 but has remained at approximately 45 years
      since then. The mean donor age increased by 7 years to 42.5 years (s.e. 0.5)
      between 1981-1991 and since then has increased at a slower rate to 43.4 years
      (s.e. 0.5) in 1998. The mean donor-recipient age difference for more than 15,000
      transplants carried out between 1990-1998 has decreased, primarily due to
      increasing donor age over this time. However, the introduction of a new Kidney
      Allocation Scheme in the UK in July 1998, part of which is aimed at minimising
      age differences, has increased the likelihood that recipients aged over 60 years
      will be allocated grafts from donors closer to their own age than previously. The
      new UK Kidney Allocation Scheme also gave children increased access to well
      matched adult organs leading to an increased mean age difference for this group
      between July-December 1998. DONOR AND RECIPIENT HLA MATCHING: Modifications to
      the Kidney Allocation Scheme introduced in January 1997 with the aim of
      increasing the number of well-matched transplants has led to a rise in 000
      mismatched grafts from 5% to 7% and favourably matched (100/010/110 mismatches)
      from 29% to 36% between 1990-1992 and 1996-1998. Over this same time the
      proportion of 2 DR-mismatched grafts has decreased from 10% to 4%. The revised
      Kidney Allocation Scheme implemented in July 1998 gave a further increase in
      priority to 000 mismatches, increasing the proportion of these transplants to 12%
      for the last half of 1998, a level which has been maintained since then.

PMID- 11512305
TI  - Organ transplantation in Latin America.
AB  - Organ transplantation is currently a form of treatment for end-stage organ
      disease in Latin America for which enthusiasm appears to be growing both in
      individual countries as well as in the whole region. The Latin-American
      Transplant Registry has been a factor in the development of communication among
      the different countries of the region and a focus for unification. Both renal and
      extra-renal organ transplantation have increased significantly during 1999 and
      for kidneys the activity is currently 12% of the world renal transplant
      statistics. Important evidence for the continuing development and maturity of
      transplantation in the region includes the number of new transplantation
      societies, the increase in the number of renal and extra-renal transplant
      programs, the development of national organ transplant registries, efforts
      towards analyzing costs and administration in transplantation and the
      incorporation of new immunosuppressants. The development of cardiac
      transplantation in Bolivia, Cuba, Paraguay, Peru, Puerto Rico and Uruguay,
      intestinal transplantation in Argentina, and liver transplantation in Bolivia all
      reflect a marked interest in organ transplantation in the different countries.
      Similarly, liver and cardiac transplantation are increasing at a very fast rate.
      End-stage organ disease is recognized as a growing health priority and organ
      donation as a critical limiting factor. Governments are directly and indirectly
      supporting transplantation initiatives. The return of trained transplant
      practitioners to their countries of origin also accounts for part of the increase
      in activity and for the organizational aspects of transplantation. The statistics
      presented in this report signify increasing maturity in the transplantation
      activities of Latin America.

PMID- 11512306
TI  - Report from the National Transplantation Pregnancy Registry (NTPR): outcomes of
      pregnancy after transplantation.
AB  - Safety of pregnancy in the female transplant recipient population must include
      consideration of 3 outcomes--mother, baby and transplanted graft. In the majority
      of female recipients studied, pregnancy does not appear to cause excessive or
      irreversible problems with graft function, if the function of the transplant
      organ is stable prior to pregnancy. However, a small percentage of recipients
      identified within each organ system may develop rejection, graft dysfunction
      and/or graft loss that may be related to the pregnancy and may occur
      unpredictably. Outcomes are not entirely similar among all organ systems, and one
      must consider risks on an individual organ basis. It appears reasonable to advise
      female recipients to wait one or 2 years after transplantation before attempting
      pregnancy to insure that function of the transplanted organ is adequate and
      stable and also to allow for stabilization of immunosuppressive medications.
      Favorable outcomes, however, have occurred when recipients have become pregnant
      less than one year from transplant, so cases must be analyzed individually.
      Immunosuppressive medications may have to be adjusted during pregnancy, and in
      some cases, rejections occur requiring additional immunosuppressive regimens
      (steroids and in several cases OKT3). Whether increasing immunosuppressive doses
      during pregnancy to adjust for falling levels lessens the rejection risk has
      never been studied prospectively. There is concern based on animal reproductive
      studies that the risk of birth defects and/or spontaneous miscarriage is
      increased in women exposed to MMF during pregnancy. Of the 9 pregnancies reported
      to the registry to date, there have been no birth defects noted among 5 liveborn
      of female recipients exposed to MMF. Data remain limited. For female recipients,
      a high incidence of low birth-weight and prematurity compared to the general
      population has been a consistent outcome, however, there has been no specific
      pattern of malformation in their newborn or any apparent increase in the
      incidence of small-for-gestational-age newborn. Long-term follow-up of children
      to date by the NTPR has been encouraging. A recent report in the literature has
      suggested impairment of immune function in newborn of CsA-treated mothers.
      Further study is needed. Some mothers have chosen to breastfeed. The potential
      risk to the newborn of ingested immunosuppressives compared with the potential
      benefits of breastfeeding is unknown and options must be discussed with the
      recipient. From earlier registry reports, recipients with deteriorating graft
      function, such as liver recipients with recurrent hepatitis C and/or other
      recipients with deteriorating graft function, appear to be at risk for worsened
      graft function with pregnancy. Outcomes of male recipient fathered pregnancies
      have been favorable and appear to be similar to the general population, but this
      group has not been as well studied as female recipients. No structural problems
      have been noted in the 38 offspring of males on MMF at the time of conception.
      Within each organ group, some female recipients have reported more than one
      pregnancy, sometimes on differing immunosuppressive regimens. If there is stable
      graft function, additional successful pregnancies are possible. Continued entries
      to the registry, especially in light of newer immunosuppressives and combinations
      of agents, are needed to continue to provide guidelines for management. The NTPR
      acknowledges the cooperation of transplant recipients and over 200 centers
      nationwide who have contributed their time and information to the registry. The
      NTPR is supported by grants from Novartis Pharmaceuticals Corp., Fujisawa
      Healthcare, Inc., Roche Laboratories Inc. and Wyeth-Ayerst Pharmaceuticals, Inc.

PMID- 11512307
TI  - The impact of transplantation on survival with kidney failure.
AB  - Although the growth in the incidence and prevalence of ESKD has slowed, there
      will nevertheless be a substantial increase in the number of patients over the
      next decade. Indeed, between 1998 and 2010 there will be a doubling in the number
      of patients in the United States treated with renal replacement therapy. There
      has also been an increase in the number of new transplants carried out every
      year. Much of the growth in the number of new transplants has been from the
      growth in living-unrelated donor transplants. Unfortunately, the rate of increase
      in the number of new transplants has not been enough to keep pace with the
      growing number of ESKD patients. As a result, the number of patients on the
      transplant waiting list continues to increase. The inability to offer more ESKD
      patients transplantation is unfortunate, since transplantation is associated with
      improved survival. Indeed, analyses of comparable patients who are placed on the
      transplant waiting list suggest that transplantation reduces the risk of death by
      roughly 50%. Thus, it is likely that the overall survival of patients with ESKD
      will improve if a greater proportion of patients receive transplants in a timely
      manner. Reducing allograft rejection and the need for repeat transplants may help
      reduce the demand for donor kidneys. However, this is unlikely to have a major
      effect on the organ shortage, since the number of repeat transplants has been
      relatively small (and constant) over the past decade. Thus, only if more
      cadaveric and living-donor kidneys are made available will more ESKD patients
      enjoy the improved survival of kidney transplantation.

PMID- 11512309
TI  - 5,000 kidney transplants--a single-center experience.
AB  - Between 6/1963 and 12/1998, 5,069 kidney transplants were done at the University
      of Minnesota. Of these, about half have been living donor, half cadaver. The
      majority (83%) have been primary transplants. Recipients were grouped in 6 eras
      based on changes in our immunosuppressive protocols--6/63-12/67 (n = 98); 1/68
      7/79 (n = 1,188); 8/79-6/84 (n = 789); 7/84-9/90 (n = 1,006); 10/90-12/95 (n =
      1,050; 1/96-12/98 (n = 718)--and their outcomes were compared. Recent eras
      contained a higher proportion of recipients aged > 50. Since the inception of the
      program, there has been a steady improvement in actuarial patient survival, graft
      survival, and death-censored graft survival. Short-term outcome for primary and
      retransplant recipients has been similar; however, long-term outcome seems worse
      for retransplant recipients. Importantly, acute rejection and infectious death
      have become rare causes of graft loss. Chronic rejection and death with function
      (most often due to a cardiovascular event) have become the predominant causes of
      graft loss. Recent changes in immunosuppressive protocols (Era VI) have included
      more aggressive attempts to maintain CsA levels > 150 ng/ml (by HPLC) in the
      first 3 months and the substitution of mycophenolate mofetil for azathioprine. As
      a result, the incidence of acute and chronic rejection has decreased and graft
      survival has improved.

PMID- 11512308
TI  - The development of sirolimus: The University of Texas-Houston experience.
AB  - The transplant team at The University of Texas-Houston has studied sirolimus from
      preclinical through pivotal Phase III trials to single-center Phase IV trials as
      we continue to refine algorithms for sirolimus therapy. The sirolimus/CsA
      combination produces a marked reduction in the occurrence and severity of acute
      allograft rejection episodes. A recently completed post hoc median effect
      analysis of drug blood concentrations displayed by patients in the 2 pivotal
      Phase III trials documented that the combination displays synergistic
      interactions. Patients in the sirolimus/CsA arms did not display an increased
      incidence of infectious or malignant complications. However, they did experience
      a range of nonimmune toxicities, including potentiation of putatively CsA-related
      adverse reactions, such as renal dysfunction and hypercholesterolemia, which
      appear to be mitigated by reduction or elimination of CsA. However,
      thrombocytopenia and to a lesser extent leukopenia and anemia appear to be
      sirolimus-related side effects. The occurrence and severity of these adverse
      reactions seem to be avoided or ameliorated in most patients by optimizing
      sirolimus exposure at concentrations (15 ng/mL or by dose reduction. Sirolimus
      thus appears to be a potent and unique agent for developing new immunosuppressive
      strategies in organ transplantation.

PMID- 11512310
TI  - Fifteen-year experience with pediatric renal transplantation at the Montefiore
      Medical Center.
AB  - At Montefiore Medical Center, 140 pediatric recipients have received 155 renal
      allografts over a 16-year period with an overall 6% mortality. Graft survival was
      not significantly different based upon race or sex of recipient. Graft survival
      was significantly better for first time transplants and the youngest recipients.
      Graft survival was significantly improved using Tacrolimus immunosuppression.

PMID- 11512311
TI  - The kidney transplant program at the Bergamo Center.
AB  - The kidney transplant program at the Ospedali Riuniti of Bergamo, Italy was
      established in 1989. Since its inception, 367 patients have been transplanted,
      including 357 kidney transplants from cadaveric donors and 10 from living-related
      donors. Overall 8-year patient and graft survival rates were 94% and 77%,
      respectively. By 1995 our unit co-ordinated the activity of the Department of
      Immunology and Clinics of Organ Transplantation, Ospedali Riuniti--Mario Negri
      Institute for Pharmacological Research, Bergamo. The dual "marginal" kidney
      transplant program in the same recipient was launched in August 1997, as a part
      of an international cooperative network which established the "Double Kidney
      Transplant Group" (DKG). To date, 19 dual kidney transplants have been
      successfully performed in our center. Four combined heart-kidney transplants and
      2 combined liver-kidney transplants have also been performed. During the past 4
      years several studies involving conventional antirejection drugs were carried
      out, particularly focussing our attention on cyclosporine (CsA) through
      pharmacokinetic and pharmacodynamic approaches: 1) a simplified method to
      evaluate daily exposure to CsA has been set up; 2) the monitoring of calcineurin
      activity in whole blood samples was evaluated as a way to optimize CsA dosing. As
      for the new immunosuppressants, studies are ongoing with mycophenolate mofetil
      (MMF). We are co-ordinating a prospective multicenter randomized trial of steroid
      sparing in kidney transplant recipients given MMF or azathioprine as a part of
      their immunosuppression therapy (MY.S.S. study). This involves 9 Italian
      transplant centers and 2 European centers. Up to now 325 patients have been
      randomized. Moreover we have set up an HPLC method for measuring plasma
      mycophenolic acid (MPA), and examined the possibility of optimizing MMF dosing by
      drug pharmacokinetic monitoring. Further studies have been addressed to chronic
      allograft nephropathy. The nature and mediators of renal lesions in kidney
      transplant patients given CsA have been explored taking into account the gene
      expression of endothelin-1, RANTES and MCP-1 in graft specimens from patients who
      had evidence of CsA nephrotoxicity, chronic rejection, or no lesions at
      histological examination. The impact of percutaneous transluminal angioplasty and
      stenting of posttransplant renal artery stenosis on renal function recovery was
      also recently examined. From this study we conclude that the procedure is safe
      and effective to normalize the functional changes sustained by hemodynamically
      significant artery stenosis. Moreover, Doppler ultrasound scanning is an useful,
      reliable, non-invasive tool to monitor the renal function response to artery
      revascularization. Thanks to the long-lasting co-operation with the Negri Bergamo
      Laboratories, we had in the past and still have an active program in experimental
      animals to investigate strategies for transplant tolerance and transplant gene
      therapy, besides addressing some issues related to the immunological barrier of
      xenotransplantation.

PMID- 11512312
TI  - Liver transplantation in the United States: a report from the Organ Procurement
      and Transplantation Network.
AB  - TRANSPLANTS AND CENTERS: Between 1988-1999 the number of annual liver transplants
      performed in the United States more than doubled, from 1,713 to 4,689; the number
      of centers increased from 59 to 117. The number of living donor, segmental, and
      multiple organ transplants also increased over time, particularly between 1997
      1999. The rate of increase in the number of centers has slowed over the last few
      years. OUTCOMES: Survival among pediatric recipients The one- and 10-year graft
      survival rates for pediatric recipients were 76% and 63%, respectively. The one-
      and 10-year patient survival rates were 85% and 78%. Patient survival did not
      decrease much after the first 2 years and graft survival stabilized after 5
      years. Some of the factors associated with increased odds of graft failure and
      patient death at 6 months after transplantation included having a previous
      transplant; being hospitalized, in the ICU, or on life support at the time of
      transplant; a creatinine level > 2 mg/dl; donor race/ethnicity; and transplant
      type. Factors associated with decreased odds of graft failure or patient death
      were recipient gender, having a metabolic disease, and a shorter than average
      cold ischemia time. Among grafts, recipients surviving the first 6 months after
      transplantation, recipient and donor race/ethnicity, primary liver disease, and
      having a previous transplant were associated with a greater relative risk of
      graft failure and mortality. The risk of graft failure was reduced for recipients
      in the ICU at the time of transplant and for those receiving organs from younger
      donors. Survival among adult recipients The one- and 10-year graft survival rates
      among adult recipients were 79% and 51%, respectively. The one- and 10-year
      patient survival rates were 85% and 59%. Survival rates decreased steadily at all
      time points following transplantation. Some of the factors associated with
      increased odds of graft failure and mortality at 6 months were increasing
      recipient and donor age; recipient and donor race/ethnicity; primary liver
      disease; having a previous transplant; being hospitalized, in the ICU, or on life
      support at the time of transplant; longer cold ischemia time; having a non
      identical recipient/donor blood type match; transplant type; and year of
      transplant. Younger recipient and donor ages, having cholestatic liver
      disease/cirrhosis, shorter cold ischemia times, and matching male recipients with
      male donors were associated with decreased odds of graft failure and mortality.
      Many of these characteristics also affected grafts and patients surviving the
      first 6 months, including recipient and donor age, recipient and donor
      race/ethnicity, primary liver disease, previous transplant, and year of
      transplant.

PMID- 11512314
TI  - Results of renal transplantation of the Hashemi Nejad Kidney Hospital--Tehran.
AB  - The first renal transplant in Iran was carried out in 1967. The renal transplant
      program severely lagged behind hemodialysis in growth until 1988. In 1988, a
      controlled LURD renal transplant program was adopted to provide kidneys for the
      large number of dialysis patients needing a renal transplant. There was no
      cadaveric donor transplant program. By the end of 1999, a total of 9,535 renal
      transplants were performed and the renal transplant waiting list of the country
      had been eliminated. In Iran's LURD renal transplant program, the Dialysis and
      Transplant Patients Association introduces the volunteer LURD to the recipient
      and the transplant team. There are no middlemen and no incentives for transplant
      teams. The government pays all of the hospital expenses for transplantation. Many
      poor patients are able to afford LURD transplantation and more than 50% of our
      LURD transplant recipients are from the poor socioeconomic class. Ethical issues
      within the program are under the strict observation of the transplant teams and
      the Iranian Society for Organ Transplantation. We have noted that many LURD
      transplant recipients had a potential LRD who did not donate for cultural reasons
      or who was reluctant to donate. In the presence of a controlled LURD renal
      transplant program, we feel it is more ethical to perform a paid renal transplant
      from volunteer LURD than a renal transplant from an LRD who may be under family
      pressure or coerced. The patient and graft survival rates reported from our unit
      are comparable to the results of renal transplants reported from centers of some
      other countries. Some patient deaths and graft losses could have been prevented
      if our transplant units were not deficient with respect to laboratory facilities
      and access to pharmaceutical agents. In April 2000, legislation recognizing brain
      death and cadaveric organ transplantation passed our parliament. Strong cultural
      barriers may limit the scale of cadaver donor transplantation in the coming years
      and we expect the programs will grow slowly. In the meantime, the LURD renal
      transplant program continues to serve the needs of many ESRD patients in Iran
      today and has allowed us to adapt this life-saving technology to our culture.

PMID- 11512313
TI  - One thousand renal transplants at Belfast City Hospital: post-graft neoplasia
      1968-1999, comparing azathioprine only with cyclosporin-based regimes in a single
      centre.
AB  - From 1968-1999, 868 recipients of 1,000 renal transplants were followed up for
      neoplasia. Altogether, 102 tumours were diagnosed in 94 patients (11.8%
      incidence). Eighty-seven occurred among 750 single and 15 occurred among 118
      multiple graft recipients. Three of 11 patients with pre-existing tumour
      developed posttransplant neoplasia, either new or recurrent. The most frequently
      seen posttransplant neoplasms were squamous carcinoma of skin, basal cell
      carcinoma (BCC), posttransplant lymphoproliferative disease (PTLD) and gastro
      intestinal (GI) cancer. Forty-one tumour-related deaths occurred (44% mortality).
      Patients on CSA (C) regimes had a greater cumulative incidence of tumour after
      transplantation than those on azathioprine and low-dose prednisolone alone (A
      regime) had--12.7% (34 of 268) vs. 4.5% (15 of 335) of those at risk up to 5
      years (relative increased rate of incidence 2.4) with more early cases of PTLD. C
      regime patients who developed neoplasia had been prescribed significantly higher
      CSA doses than tumour-free controls (4.5 vs. 3.4 mg/kg/day; p = 0.014). Patients
      who made a late conversion from the A to the C regime subsequently developed more
      neoplasms than nonconverted controls (25.7% vs. 12%), mainly due to early and
      often aggressive squamous carcinoma. Transplant survival figures were similar for
      both A- and C-regime groups. These findings suggest that current CSA doses are
      higher than are necessary for optimal graft survival and thus increase the risk
      of early neoplasia without any compensatory advantage. A dose reduction of CSA to
      less than 3.5 mg/kg/day in long-surviving, stable graft recipients should reduce
      tumour risk without imperilling function. Late conversion from the A to the C
      regime should be avoided where possible and CSA doses in this situation kept to a
      minimum.

PMID- 11512315
TI  - Simultaneous pancreas-kidney (SPK) and pancreas living-donor kidney (SPLK)
      transplantation at the University of Maryland.
AB  - The evolution of enteric and portal venous drainage, better immunosuppression,
      and better patient care has elevated pancreas transplantation with dramatically
      improved results. At our center, long-term graft survival and rejection has
      significantly improved with portal venous drainage, which has become our gold
      standard. This improvement is exemplified by the excellent one-year patient and
      graft survival rates for SPLK transplants. SPLK has proven to be an ideal
      approach in uremic Type 1 diabetic patients with living donors and should become
      the procedure of choice for that population. Moreover, the improved monitoring of
      rejection has allowed a similar success of pancreas transplantation alone in non
      uremic patients with brittle diabetes. The treatment of diabetes mellitus has
      room for great improvement, however, and there is no question that islet
      transplantation, xenotransplantation, and the pursuit of immunologic tolerance
      will play an extremely important role in that endeavor.

PMID- 11512316
TI  - Portal-enteric pancreas transplantation at the University of Tennessee, Memphis.
AB  - The UT Memphis group has made a number of important contributions to the field of
      PTX, including: 1) pioneering studies on the effects of PTX on autonomic
      neuropathy, 2) comprehensive reports dealing with quality of life after PTX, 3)
      seminal studies on the metabolic effects of PTX with portal venous delivery of
      insulin, 4) refining and perfecting a novel technique of PTX with portal venous
      drainage of insulin and primary enteric drainage of the exocrine secretions, 5)
      describing a safe outpatient percutaneous technique of pancreas allograft biopsy,
      6) developing the use of glucose tolerance for rejection surveillance, and 7)
      managing PTX patients with biopsy-directed immunosuppression and no anti
      lymphocyte induction therapy. The P-E technique has the potential to become the
      standard of care in the near future because it is more physiologic, normalizes
      carbohydrate and lipid metabolism, and minimizes complications attributed to the
      transplant procedure. In addition, we have been actively involved in studying new
      immunosuppressive regimens in order to improve and simplify the care of the PTX
      recipient. We believe that PTX will remain an important treatment option for IDDM
      until other strategies are developed that can provide equal glycemic control with
      less or no immunosuppression and less overall morbidity.

PMID- 11512317
TI  - Pancreas transplantation at Northwestern University.
AB  - The collective advances made by many groups have significantly improved the
      results of pancreas transplantation. We have focused on the development of safe
      and effective immunotherapy, including a new protocol of rapid withdrawal of
      corticosteroids, the analysis of surgical technique of pancreas exocrine drainage
      on outcome and the role of SPK transplantation in patients with significant
      cardiovascular disease. We have found that multimodal immunotherapy including
      induction with tacrolimus-based maintenance combined with either MMF or
      sirolimus, with or without corticosteroids, resulted in excellent patient and
      graft survival rates with low rates of rejection. In this setting, enteric
      drainage was preferable to bladder drainage because of a lower rate of
      complications leading to hospital readmissions. Careful pretransplant screening
      for cardiovascular disease should be routinely performed for all SPK candidates.
      If successful coronary revascularization can be achieved, these patients can
      safely undergo SPK transplantation, with 5-year outcomes similar to those for
      recipients without coronary disease. Finally, we have observed that pancreas
      transplantation has an important ameliorating effect on hypertension that is
      independent of the method of pancreas exocrine drainage.

PMID- 11512318
TI  - Liver transplantation at Mount Sinai.
AB  - Nearly 2000 liver transplants have been performed over the past 12 years at Mount
      Sinai, with a recent exponential growth in living donor surgeries. Living-donor
      liver transplantation has emerged as an important option for our patients with
      end-stage liver disease. We are only beginning to recognize fully the advantages
      that 'scheduled' liver transplantation can offer. In this era of severe cadaver
      organ shortages, living donation offers patients the option of liver replacement
      in a timely fashion, before life-threatening complications of hepatic failure
      and/or carcinoma progression prohibit transplantation. The next era of
      transplantation at Mount Sinai will bring significant increases in the number of
      transplants performed with living donors, with projections of over 50% of the
      total transplants each year expected to involve living donations. We are
      committed to offering this option while recognizing that donor safety remains
      paramount and cannot be overemphasized. Proper donor and recipient selection, as
      well as surgical experience are imperative to success with this technically
      demanding procedure. Recurrent disease after transplantation, particularly with
      hepatitis C, remains a challenge clinically. Further investigations into the
      pathogenesis of the rapid progression of recurrent hepatitis C need to be
      addressed. Living donor transplantation could be an important option for these
      patients and would allow timely transplantation and the potential for improved
      survival in patients with hepatocellular carcinoma.

PMID- 11512319
TI  - Eighteen years of experience with adult and pediatric liver transplantation at
      the University of Tennessee, Memphis.
AB  - 1. Since its inception, the liver program at UT Memphis has been striving to
      serve its population by stressing access, technical innovation, and by its focus
      on quality of life. The results for both adult and pediatric transplants over the
      past 18 years demonstrate that small and medium-sized programs can function
      efficiently and are valuable for their local communities. 2. Patient and graft
      survival rates exceeded 85% in the pediatric population in the first year with
      the 5-, 10-, and 15-year results above 75%. 3. Patient and graft survival rates
      in adults were 83% at one year, 68% at 5 years, and 60% at 10 years. 4.
      Innovative techniques in liver transplantation have had a dramatic impact on
      accessibility of pediatric recipients to liver transplantation and recently are
      becoming crucial for select populations of adults requiring expedited
      transplantation.

PMID- 11512320
TI  - The University of Toronto Liver Transplant Program: Toronto General Hospital,
      Hospital for Sick Children.
AB  - The University of Toronto Liver Transplant Program began in 1985 at a time when
      the procedure had already evolved from an experimental form of surgery to an
      accepted treatment for many forms of liver failure. The program was established
      not only to provide clinical care for patients but also to address academically
      the barriers that impeded success. The program brought together experts in
      medicine, surgery, pathology, and the basic sciences of immunology, virology and
      molecular biology. Significant advances over the past decade and a half in
      immunosuppressive drugs and monitoring, patient selection, and infectious
      management have contributed to markedly improved patient and graft survival
      rates. Nevertheless, we continue to face 2 major challenges: a growing scarcity
      of donor organs, a problem partially addressed through development of living
      related liver donation, and recurrent viral hepatitis. We expect to remain on the
      forefront of ongoing research to provide solutions to these and other barriers to
      the full deployment of liver transplantation in the year 2000.

PMID- 11512321
TI  - Paul Brousse Liver Transplantation: the first 1,500 cases.
AB  - During the past 16 years, more than 1,500 liver transplants were performed at
      Paul Brousse Hospital. The overall patient survival rates were 83% at one year
      and 65% at 10 years. Our group has pioneered a variety of new approaches to liver
      transplantation, including: 1. Anti-HBs (HBIG) prophylaxis for the prevention of
      HBV recurrence. To date more than 270 patients have received long-term treatment
      and the overall 10-year recurrence rate was 27%. 2. Transplantation for
      hepatocellular carcinoma of the cirrhotic liver in patients with uni- or
      binodular HCC (< 3 cm). Survival for transplanted patients was 83% compared with
      18% if the liver was resected. 3. Transplantation for familial amyloidotic
      polyneuropathy (FAP). More than 60 patients had 5- and 10-year survival rates of
      85% and 83%, respectively. Ten livers obtained after hepatectomy from these FAP
      patients were transplanted as "domino" living donor livers to patients with
      unresectable liver cancers with satisfactory short-term results. 4. Reduced-size
      liver grafts have been used successfully to reduce pretransplant mortality and
      posttransplant morbidity and mortality by shortening the wait for our pediatric
      patients. 5. Split-liver transplantation has increased the number of
      transplantable livers by 28%. 6. Split-liver transplantation for 2 adults. Using
      optimal livers we have transplanted 34 adults with grafts prepared by ex-vivo or
      in-situ splitting with good survival rates. 7. Adult-to-adult living-related
      donor liver transplantation. In 2000, 7 adult-to-adult living donor transplants
      were performed with no complications from the donor surgeries. One recipient was
      retransplanted for arterial thrombosis, but all 7 recipients are alive at home.
      The Paul Brousse Hospital is committed to exploring new technologies to improve
      the outcome of and expand the indications for liver transplantation. We have
      taken a surgical approach to the organ shortage, finding new ways to serve the
      most patients with the limited number of livers available.

PMID- 11512322
TI  - Adult liver transplantation: the Universite Catholique de Louvain experience.
AB  - Liver transplantation remains a formidable surgical and medical procedure. The
      larger single centre experience confirms that standardization of perioperative
      care and simplification of the surgical procedure markedly improve results.
      Further efforts must be made in relation to immunosuppressive therapy in order to
      minimize late morbidity and mortality.

PMID- 11512323
TI  - Sixteen-year experience with 1,000 heart transplants at UCLA.
AB  - 1. The consecutive pre- and post-1994 eras have demonstrated improved survival
      for all age groups. This is linked to improved preservation methods, surgical
      technique and immunosuppression agents. 2. The use of marginal donor hearts for
      Status I and alternate elderly patients has followed the model of matching donor
      and recipient risk without affecting patient outcome and minimized the use of
      implantable assist devices. 3. A donor history of systemic gram-negative
      infection, hypertension, or traumatic intracranial bleeds was an important marker
      for risk. Younger age and shorter ischemia time could compensate for other
      hazards. 4. Heart transplantation in carefully selected elderly recipients
      yielded clinical results similar to those of younger patients with less
      rejection. 5. An adult alternate recipient list proved useful to prevent
      diversion of standard donors away from younger recipients. 6. Retransplantation
      for TCAD is acceptable but much less satisfactory for acute graft failure. 7.
      Trends show an increase in the use of implantable devices; refinement in
      technology for mechanical assist and replacement is forthcoming.

PMID- 11512324
TI  - Worldwide thoracic organ transplantation: a report from the UNOS/ISHLT
      International Registry for Thoracic Organ Transplantation.
AB  - Based on data reported to the UNOS/ISHLT International Registry for Thoracic
      Organ Transplantation, we showed that: 1. The number of heart transplant
      operations performed in the United States has decreased by 164 procedures between
      1998 (2,346) and 1999 (2,182). The number of lung transplants increased by 13 in
      1999 to 877. 2. The most frequently reported indication for heart transplantation
      in the US is coronary artery disease (44.8%). For other thoracic transplants, the
      most frequently reported indications include cystic fibrosis (35.5%) for double
      lung, emphysema/COPD (49.7%) for single lung and congenital heart disease (46.6%)
      for heart-lung. The most frequently reported diagnoses for thoracic
      transplantation outside the US include cardiomyopathy (43.8%) for heart, cystic
      fibrosis (33.4%) for double-lung, emphysema/COPD (26.6%) for single-lung and
      primary pulmonary hypertension (24.8%) for heart-lung transplants. 3. US heart
      transplant recipients are predominately male (76.7%), between 50 and 64 years of
      age (51.3%) and white (81.4%). US lung transplant recipients are also
      predominately between 50 and 64 years of age (44.7%) and white (89.9%), but
      unlike heart recipients are more likely to be female (51.2%). No meaningful
      variance from the US recipient demographic profile is noted for the non-US
      recipients during the same time period. 4. Pediatric recipients (< 18 years of
      age) received 10.9% of the reported heart transplants and 6.2% of reported lung
      transplants. 5. One-year survival for thoracic transplants performed in the US is
      82.4% for heart, 74.1% for lung and 62.0% for heart-lung. Five-year survival for
      US thoracic transplants is 66.8% for heart and 43.2% for lung. 6. Long-term
      patient survival rates are: 22.5% at 17 years for heart, 20.8% at 10 years for
      lung and 24.3% at 13 years for heart-lung recipients. 7. The most important risk
      factor for mortality of US heart recipients at one month, one year and
      conditionally at 5 years after transplantation was receipt of a previous heart
      transplant. Significant short-term risk factors include donor age, recipient age
      and ischemic time. Substantial long-term risk factors include older donor age,
      recipient age, recipient race and diagnosis. 8. The factors having the most
      significant impact on lung mortality at all time points are related to either the
      patient's medical condition (e.g., in the ICU prior to transplant, requiring
      mechanical ventilation) or diagnosis. 9. Mechanical ventilation, recipient race
      and recipient age have the largest impact on heart-lung mortality. 10. For heart
      and lung recipients, the major cause of hospitalization during the first year
      after transplantation is infection alone.

PMID- 11512325
TI  - Clinical cardiac and pulmonary transplantation: the Hannover experience.
AB  - Thoracic organ transplantation has evolved from an experimental to a standard
      treatment modality for patients suffering from end-stage heart and lung failure.
      Based on our experience after 1,033 heart, lung, and heart-lung transplantation
      procedures performed at the Hannover Thoracic Organ Transplant Program, we
      report: 1. Survival rates following thoracic organ transplants were similar and
      ranged from 76-81% after one year. 2. The one-, 5-, 10- and 15-year survival
      rates for heart transplant recipients were 81%, 70%, 52% and 33%, respectively.
      3. The 9-year survival rate for bilateral-lung transplant recipients (56%) was
      significantly better than that for single-lung recipients (36%, p < 0.05). 4.
      Heart-lung recipients had the poorest long-term survival rate in our program--18%
      surviving after 9 years. 5. Retransplantation has been an effective treatment for
      chronic graft dysfunction in lung transplant recipients, but was less successful
      when used to treat acute graft failure. The one-year regraft survival rate was
      74% among 15 patients retransplanted for chronic graft failure compared with only
      50% for 4 patients retransplanted for acute failure.

PMID- 11512326
TI  - Hematopoietic stem cell transplantation in the new millennium: report from City
      of Hope National Medical Center.
AB  - Progress in the in the field of human stem cell transplantation (HSCT) has led to
      a reduction in transplant-related toxicities and an improvement in survival
      rates. In the allogeneic setting, conditioning regimens containing FTBI and high
      dose VP-16 produce high rates of long-term progression-free survival in patients
      with AML and ALL. Because of more rapid engraftment, peripheral blood stem cells
      are increasingly being used for allogeneic HSCT, however, longer follow-up will
      be required to determine whether there are differences in overall survival and
      long-term complications such as chronic graft-versus host disease (GVHD). Results
      of autologous transplantation for acute leukemias are improving as new strategies
      are used to decrease the risk of relapse. For diffuse aggressive NHL, high-dose
      therapy and autologous HSCT has been established as a potentially curative
      therapy when performed at the time of relapse or as part of the frontline
      treatment in selected patients with poor prognostic features at presentation.
      Patients with HIV-associated NHL may also benefit from autologous HSCT. In other
      subtypes of NHL such as mantle cell lymphoma and low-grade lymphoma, the curative
      potential of autologous transplantation is less certain and the graft-versus
      lymphoma effect which can be seen in allogeneic HSCT may be required for cure of
      these histologic subtypes. Our current research efforts focus on reducing the
      risk of relapse as well as acute and long-term complications.

PMID- 11512327
TI  - Organ transplantation in Argentina.

PMID- 11512328
TI  - Renal transplantation in Australia and New Zealand 1963 to 1999.
AB  - The main feature of transplantation in Australia and New Zealand over the last
      few years has been the increasing proportion of living donor transplants on the
      background of a cadaveric organ donation rate, which is very low by international
      standards. The increase in living donor transplants has occurred predominantly as
      a result of an increase in the number of unrelated grafts. The success rate in
      transplantation in Australia is excellent with a one-year primary cadaveric graft
      survival rate of around 90% for each year since 1994 to the present. The
      accumulated one-year graft survival for unrelated living-donor grafts performed
      between 1990-1999 was 91.6%, which compares favourably with graft survival for
      all cadaveric grafts over the same period of 86.5%.

PMID- 11512329
TI  - Organ transplantation in Brazil.

PMID- 11512330
TI  - Kidney transplantation in Chile.

PMID- 11512331
TI  - Kidney transplantation at the University Hospital Zagreb, Croatia.

PMID- 11512332
TI  - Renal transplantation in Cyprus.

PMID- 11512333
TI  - Kidney transplantation activity and outcome in Denmark 1990-1999.
AB  - 1. During the period 1990-1999, 1,715 renal transplants were performed in
      Denmark, corresponding to 31.8 per million population per year. Seventy-five per
      cent were cadaver donor transplants; in 25%, a living donor kidney was used. 2.
      Living donors of 437 kidneys were mainly parents (54%) and siblings (36%). In 20
      transplants, a kidney from a living-unrelated donor was used. 3. The overall
      actuarial patient survival rates at one and 5 years were 91.0% and 78.2%,
      respectively. The major causes of recipient death were cardiovascular disease and
      infection. 4. The overall actuarial graft survival rates at one and 5 years were
      81.4% and 62.0%, respectively. The major single causes of graft loss were
      rejection (41%) and recipient death (32%). Graft survival has improved during the
      decade.

PMID- 11512334
TI  - The Egyptian renal transplant experience.

PMID- 11512335
TI  - Kidney transplantation in France.

PMID- 11512336
TI  - Renal transplantation in Greece.

PMID- 11512337
TI  - Kidney transplantation in Iraq.

PMID- 11512338
TI  - Organ transplantation in Israel.

PMID- 11512339
TI  - Organization and results of kidney transplant activity in Italy during 1995-99.

PMID- 11512340
TI  - Kidney transplantation in the north Italy transplant program.

PMID- 11512341
TI  - Status of kidney transplantation in Japan.

PMID- 11512342
TI  - Kidney transplantation in Korea: past and present.

PMID- 11512343
TI  - Kidney transplantation in Mexico.

PMID- 11512344
TI  - Kidney transplantation in Pakistan.

PMID- 11512345
TI  - Organ transplantation in the Philippines.

PMID- 11512346
TI  - Kidney transplantation in Poland.

PMID- 11512347
TI  - Kidney transplantation in Portugal.

PMID- 11512348
TI  - Kidney transplantation in Puerto Rico.

PMID- 11512349
TI  - Renal transplants in Russia.

PMID- 11512350
TI  - Renal transplantation in South Africa.

PMID- 11512352
TI  - Kidney transplantation in Switzerland.

PMID- 11512351
TI  - Kidney transplantation in Spain--1990-2000.

PMID- 11512353
TI  - Transplantation in Taiwan.

PMID- 11512354
TI  - Kidney transplantation in Thailand.

PMID- 11512355
TI  - Renal transplantation in Turkey.

PMID- 11512356
TI  - Kidney transplants in Uruguay.

PMID- 11512357
TI  - Annual literature review--clinical transplants 2000.

PMID- 11512358
TI  - Pancreas transplant outcomes for United States (US) cases reported to the United
      Network for Organ Sharing (UNOS) and non-US cases reported to the International
      Pancreas Transplant Registry (IPTR) as of October, 2000.
AB  - As of October 2000, > 15,000 pancreas transplant had been reported to the IPTR, >
      11,000 in the US and > 4,000 outside the US. An era analysis of US cases from
      1987-2000 showed a progressive improvement in outcome (p < 0.04), with pancreas
      transplant graft survival rates (GSRs) going from 72% to 82% at one year for SPK
      cases, from 52% to 74% for PAK cases, and from 47% to 76% for PTA cases. The
      improvements were due both to decreases in technical failure (TF) rates (overall
      from 16% to 7%) and immunological failure rates (going from 8% to 2% for SPK,
      from 27% to 6% for PAK, and from 37% to 12% for PTA cases). The proportion of
      recipients > 45 years old increased from 5% to 25%, and the improved outcomes
      encompassed the older patients as well. In patients > 45 years old, SPK pancreas
      GSRs at one year increased from 62% to 78% (p < 0.002). Pancreas GSRs were also
      similar for recipients reported to have Type 1 or Type 2 diabetes (at one year,
      84% and 83%, respectively for 1996-2000 SPK transplants), the latter designated
      in 3% of the recipients. Contemporary pancreas transplant outcomes were
      calculated separately for 1996-2000 US and non-US cases. US patient survival
      rates at one year were > or = 94% in each recipient category, with one-year
      pancreas GSRs of 84% for SPK (n = 3,697), 76% for PAK (n = 696), and 71% for PTA
      (n = 300) (p = 0.0001). The immunological graft failure rates for 1996-2000 US
      SPK, PAK and PTA cases were 2%, 6%, and 8% at one year (p = 0.001). There was a
      progressive increase in the use of ED (as opposed to BD) for duct management, to
      > 50% for 1996-2000 US SPK transplants. Approximately 20% of US SPK ED
      transplants had venous drainage via the portal system. Pancreas GSRs were not
      significantly different for 1996-2000 ED (n = 1,940) and BD (n = 1,541) US SPK
      transplants (83% and 84%, respectively, at one year), nor was there a difference
      in pancreas GSRs for systemic (n = 1,509) versus portal (n = 411) venous drained
      ED SPK transplants (83% for both at one year). Kidney GSRs were also not
      significantly different for ED versus BD US SPK cases, 93% versus 91% at one year
      (p = 0.13). Duct management did matter for solitary (PAK and PTA) pancreas
      transplants (P < or = 0.07). Pancreas GSRs for PAK recipients were 77% at one
      year for BD (n = 359) versus 67% for ED (n = 306) US transplants; for PTA 75% (n
      = 174) versus 63%. However, BD transplants were associated with a 12% conversion
      rate to ED by 2 years after transplantation. Analyses of outcome by
      immunosuppression for US cases showed pancreas GSRs ranged from 77% to 88% at one
      year, but were highest in SPK recipients given anti-T-cell agents for induction
      and CSA-MMF for maintenance immunosuppression. For PAK and PTA recipients, those
      given anti-T-cell agents for induction and TAC-MMF for maintenance
      immunosuppression had the highest GSRs: 78% and 78%, respectively, at one year
      for BD pancreas transplants (vs. 85% in BD SPK recipients similarly
      immunosuppressed, P > 0.08). In regard to non-US cases, the overwhelming majority
      were in the SPK category (n = 676 for 1996-2000), with a one-year pancreas GSR of
      84%, not significantly different than for US cases. In summary, pancreas
      transplant graft survival rates were > 70% in the solitary (PAK and PTA) and >
      80% in SPK recipients during the last 4 years of the 20th century. These outcomes
      culminate a third of a century of application for the treatment of diabetes
      mellitus.

PMID- 11512359
TI  - Impact of delayed graft function and acute rejection on kidney graft survival.
AB  - 1. From 1991 to 1998, the incidence of DGF remained at 21% of all kidney grafts
      (n = 86,682) reported to the UNOS Scientific Transplant Registry. In contrast,
      percentages of early acute rejection (EAR) and late acute rejection (LAR) have
      dropped precipitously to half their starting values. (EAR started at 37% and
      dropped to 18%, and LAR started at 11% and dropped to 5%.) 2. Among discharged
      recipients, DGF was associated with increased EAR (odds ratio = 1.7) within 6
      months of transplant; whereas, EAR (odds ratio = 4.7) but not DGF (odds ratio =
      1.1) was associated with increased LAR for recipients from 6 months to one year
      after transplantation. 3. Non-immune factors (e.g., duration of pretransplant
      dialysis, donor age, and cold ischemia time) primarily influenced the risk of
      DGF, and immune factors (e.g., recipient race, recipient age, HLA) mainly
      determined the risk of EAR and LAR. 4. DGF, EAR and LAR were independent risk
      factors for long-term graft loss. DGF and LAR exhibited the strongest influences,
      reducing half-lives by 30% and 50%, respectively. 5. Some long-term risk factors
      demonstrated consistent effects regardless of DGF and/or LAR. For example, Black
      recipients always had poor long-term GS. On the other hand, some risk factors,
      mostly immune-type factors, exhibited effects only in the absence of DGF (e.g.,
      recipient sex, age and HLA matching). Many non-immune factors exhibited long-term
      effects only in the absence of LAR (e.g., donor age, cause of donor death). 6.
      Strategies aimed at reducing both DGF and AR are necessary to improve the long
      term outcome of kidney transplants.

PMID- 11512360
TI  - Maintenance immunosuppression.
AB  - 1. The increased utilization of Neoral, Tacrolimus and mycophenolate mofetil
      correlated with the dramatic decrease in rejection rates in the 1990s. 2. The 4%
      difference in the incidence of rejection noted for recipients treated with
      Tacrolimus (20%) compared with Neoral (16%) corresponded to a 34% increased odds
      ratio in the multivariate analysis. The risk of graft loss and patient death were
      similar for the 2 calcineurin inhibitors. 3. Almost every renal transplant
      recipient received mycophenolate mofetil in 1999. This agent reduced the risk of
      3-year graft loss by 60% and halved the risk of death compared with azathioprine.
      4. Use of solumedrol as a corticosteriod increased from 26-67% in the 1990s, but
      this change in practice did not significantly impact outcome. 5. Although
      recipients given induction ATG or OKT3 had increased risk of graft failure, these
      recipients more likely were sensitized or required early dialysis. 6. The risk of
      rejection was 90% higher for recipients with 5-6 HLA mismatches than those with 0
      A,B,DR mismatches. Recipients with a poorly HLA-matched kidney had 50% increased
      risk of graft loss within 3 years compared with HLA-matched transplants.

PMID- 11512361
TI  - The HLA-matching effect in different cohorts of kidney transplant recipients.
AB  - 1. The HLA-matching effect in Type 1 diabetic patients applied only to those
      receiving a kidney alone. Those receiving simultaneous pancreas transplants did
      not benefit significantly from HLA-matching, although graft survival was high.
      Nevertheless, an HLA-matching effect could be shown for grafts from cadaver
      donors who were 25-35 years of age. Grafts from older donors apparently were more
      vulnerable to diabetic complications. The highest graft survival in diabetic
      patients was obtained with HLA-identical living donor grafts-60% at 10 years,
      which was in marked contrast to the 35% survival rate of HLA-mismatched cadaver
      donor grafts. 2. Functional graft survival analysis (censoring deaths) of Type 1
      diabetics showed that graft survival was low because of deaths, presumably
      resulting from diabetic complications. 3. The HLA-matching effect was modest for
      focal glomerulonephritis patients. However, a small HLA-matching effect was noted
      in retransplants from cadaver donors and grafts from living donors. 4. Patients
      with polycystic kidney disease had the highest overall graft survival rates in
      all HLA-mismatch categories. Zero-ABDR-mismatched first cadaver transplants had a
      60% ten-year survival rate and a 78% survival rate from HLA-identical living
      donors. 5. Patient survival in all the disease groups was not affected by HLA
      matching. Graft failure and return to dialysis apparently did not affect survival
      of patients. 6. Overall graft survival rates have improved markedly with newer
      immunosuppressants and improved patient care. The 3-year graft survival rate for
      the worst mismatches improved from 67% in 1987-90 to 73% for 1990-92 transplants
      to 73% for 1992-94, 78% for 1994-96, and 80% for transplants performed in 1996
      98. 7. Projected 10-year graft survival for patients transplanted since 1994 was
      64% for 0-HLA-mismatched grafts and 47% for 5-6 antigen-mismatched transplants--a
      17% differential. Thus, despite newer immunosuppression, HLA matching continues
      to be an important factor.

PMID- 11512362
TI  - The OPTN waiting list, 1988-1999.
AB  - 1. On October 31, 2000, there were 77,999 registrations on the combined UNOS
      waiting list. Of these, 63% were awaiting kidney transplantation, and 21.5% were
      awaiting liver transplantation. 2. The majority of patients on the UNOS waiting
      list on October 31, 1999 were of blood type O (52%), White (56%) and male (58%),
      and awaiting their first transplant (87%). 3. Median waiting times have increased
      steadily for nearly every organ since 1988, especially for liver, kidney, and
      lung registrants. 4. In general, the percent transplanted within one year of
      listing is highly influenced by blood type and medical urgency. Patients awaiting
      heart, pancreas, and intestinal transplants experience the highest probability of
      receiving a transplant within one year. 5. Since 1988, death rates per patients
      waiting at risk have declined for most patients awaiting life-saving organs and
      have remained relatively stable for those awaiting a kidney transplant. Deaths
      are highest among intestinal patients, but appear to be declining.

PMID- 11512363
TI  - Organ donation in the United States: 1990-1999.

PMID- 11512364
TI  - The relevance of proficiency testing for laboratories involved in cadaveric organ
      transplantation and its consequences for graft survival.
AB  - Organ exchange organizations such as Eurotransplant allocate organs on the basis
      of histocompatibility testing results. For this reason it is essential that all
      data reported by the affiliated laboratories are accurate and reliable. The
      Eurotransplant Reference Laboratory (ETRL) organizes proficiency testing schemes
      for the tissue-typing centers of the respective renal transplantation units
      participating in Eurotransplant. Each year, the ETRL sends out 8 peripheral blood
      samples of healthy blood donors for serological typing and crossmatching, 16 sera
      to screen for the presence and definition of HLA alloantibodies and 20 DNA
      samples for molecular typing to the 49 participating centers. The results are
      collected centrally and reported back to the participants in an open way. These
      exercises show that the quality of HLA typing, screening and crossmatching
      improved significantly over the years. In particular, the introduction of
      molecular typing for HLA-DR resulted in an increase of reliability. The clinical
      relevance of a reliable HLA typing was demonstrated in a selected group of
      transplants, the zero HLA-A,-B,-DR- mismatched group. After retyping the donors,
      146 of the 3,458 matched transplants appeared to have a mismatch and those
      transplants had a significantly lower graft survival rate. A continuing problem,
      however, is the result of screening for panel reactive antibodies (PRA), where
      the percentage PRA reported for each serum varies significantly from center to
      center. The results indicate that the use of a PRA value for classification of
      patients and allocation of organs should be revisited.

PMID- 11512365
TI  - Prognostic factors of hyperglycemic hyperosmolar nonketotic state.
AB  - BACKGROUND: To delineate the prognostic factors of patients suffering from
      hyperglycemic hyperosmolar nonketotic state (HHNK) in Taiwan. METHODS: We
      reviewed the charts of patients who had been admitted to the Division of
      Endocrinology and Metabolism of Kaohsiung Veterans General Hospital from 1992 to
      1998 due to HHNK. General and clinical data were collected. The influential
      factors for prognosis were determined. RESULTS: One hundred and nineteen patients
      fulfilling the criteria of HHNK were included in our study. The mean age was 67.8
      +/- 11.7 years with male predominance. Twenty-nine patients died which produced a
      fatality rate of 24.4%. Eighty-six (72.3%) cases occurred in patients with known
      diabetic history, while another thirty-three (27.7%) occurred in patients with no
      diabetic history. Most patients received oral antidiabetic drugs before HHNK
      episodes. The patients who died had shorter length of inpatient stay than did
      survivors. The leading precipitating factor was infection (57.1%), followed by
      poor compliance of medication (21.0%) and undiagnosed diabetes (10.9%). Fifty
      patients (42%) had a history of stroke. The risk factors for death included
      precipitation of HHNK by infection and low Glasgow coma scale (GCS) on admission.
      Old age itself did not contribute to death. Severity of hyperglycemia or
      hyperosmolarity was also not an important prognostic factor. Multiple logistic
      regression revealed that low GCS on admission was the most influential factor of
      leading to death. Most of the patients who died did so due to underlying
      precipitating factors. CONCLUSIONS: Neither age nor osmolarity, but underlying
      precipitating factors and state of consciousness were the most influential
      factors affecting the prognosis of HHNK.

PMID- 11512366
TI  - Differential telomerase expression and telomere length in primary intracranial
      tumors.
AB  - BACKGROUND: Telomerase activity and telomere length have been shown to be
      involved in controlling cell proliferation and regulating cell senescence. The
      authors examined telomerase activity and telomere length in intracranial tumors
      to determine the clinicopathological behavior of primary intracranial tumors with
      respect to telomerase expression and alteration of telomere length. METHODS:
      Telomerase activity was examined in 139 brain tumor samples. Telomere length was
      examined in 138 of the 139 samples. These tumors included 61 meningiomas, 27
      schwannomas, 19 high-grade neuroepithelial tumors, and 32 low-grade
      neuroepithelial tumors. Telomerase activity was measured with a telomerase
      polymerase chain reaction, enzyme-linked immunosolvent assay kit. Telomere length
      was examined by Southern blot analysis for the terminal restriction fragment
      length. RESULTS: Telomerase activity was detected in 39.2% (20/51) of the
      neuroepithelial tumors. Detection rates were 47.4% (9/19) for anaplastic
      astrocytomas and glioblastomas and 34.4% (11/32) for low-grade neuroepithelial
      tumors. However, detectable telomerase activity was found in 30.8% (4/13) of
      atypical or malignant meningiomas, but was not detected in any schwannomas. There
      was a highly significant difference in the telomerase detection rate in
      neuroepithelial or non-neuroepithelial tumors (p = 0.001). Telomere elongation
      was found in 11.7% (7/60) of all meningiomas, 46.1% (6/13) of atypical or
      malignant meningiomas, and 14.8% (4/27) of schwannomas. Elongation of telomere
      length was detected in 12.6% (11/87) of the cases and 23.5% (12/51) in
      neuroepithelial tumors. This difference was also significant (p < 0.05). Telomere
      length was reduced in the majority, (75%, 3/4) of malignant or atypical
      meningiomas with detectable telomerase activity, but only 45% (9/20) of the
      neuroepithelial tumors. CONCLUSION: These results indicate that telomerase
      activation may be a critical step in the pathogenesis of intracranial tumors.
      Telomere length elongation also indicates a high potential for malignant behavior
      in these tumors.

PMID- 11512367
TI  - Reconstruction of acquired nasolacrimal duct obstruction.
AB  - BACKGROUND: Acquired nasolacrimal duct obstruction is a common condition in
      patients who visit otolaryngologists and ophthalmologists. These patients often
      complain of epiphora and blurred vision, and sometimes they suffer from acute or
      chronic dacryocystitis. Other causes of acquired nasolacrimal duct obstruction
      include trauma, chronic inflammation, post-operative iatrogenic procedures, and
      tumors. Reconstruction of an acquired nasolacrimal duct obstruction provides
      great improvement in a patient's quality of life and satisfaction both
      functionally and cosmetically. In this paper, we report on surgical techniques of
      endonasal endoscopic dacryocystorhinostomy and traditional external
      dacryocystorhinostomy. A rare case of mechanical compression of the lacrimal sac
      by a frontal mucocele is also presented. METHODS: From 1989 through 1999, we
      treated 26 patients, 10 men and 16 women, with 28 cases of acquired nasolacrimal
      duct obstruction. Two patients had bilateral involvement. Five cases were
      complications of sinus surgery. Ten cases were acute dacryocystitis due to
      chronic nasolacrimal duct obstruction. One case of nasolacrimal duct obstruction
      was caused by a frontal mucocele. The remaining cases were non-specific
      nasolacrimal duct obstruction. Of all patients, 26 cases underwent external
      dacryocystorhinostomy, 1 underwent endonasal endoscopic dacryocystorhinostomy,
      and 1 case underwent frontal sinus dacryocystorhinostomy. RESULTS: Only 1 patient
      out of 28 cases that underwent surgery suffered from obstruction after external
      dacryocystorhinostomy for 3 months; 25 patients attained both anatomical success
      and clinical improvement. CONCLUSION: The success rates were high for patients
      undergoing either traditional external dacryocystorhinostomy or endonasal
      endoscopic dacryocystorhinostomy.

PMID- 11512368
TI  - Computed tomography-guided percutaneous transpedicular biopsy of the thoracic
      spine.
AB  - BACKGROUND: Despite the recent, widespread use around the world of computed
      tomography (CT)-guided spinal biopsy for presurgical evaluation, its use has
      remained uncommon in Taiwan. Using 9 patients, we attempted to evaluate the
      safety of its use for the thoracic spine biopsy. METHODS: In the past 3 years
      (May 1996 to May 1999), 9 patients with known thoracic or multiple spinal lesions
      underwent CT-guided biopsy. The patients comprised 4 men and 5 women; with ages
      ranging between 28 and 85 years. For the transpedicular approach, patients were
      laid prone on the CT table. A trephine bone biopsy needle set was used after
      local anaesthesia. The specimens obtained had tissue pathology and/or
      bacterial/tuberculosis (TB) culture. RESULTS: Excellent results were achieved in
      8 of the 9 patients, with no significant procedure-related complications. Among
      them, 2 were diagnosed as metastatic carcinomas; 3 as osteoporotic compression
      fractures; 2 were proved to be bacterial or tuberculosis spondylitis and the last
      one was a healing fracture. CONCLUSION: CT-guided transpedicular trephine biopsy
      of the thoracic spine is a safe and effective method for preoperative evaluation
      of various thoracic spinal disorders. Based on the biopsy results, more effective
      treatment regimens were prescribed and, in turn, better outcomes were expected.

PMID- 11512369
TI  - Hemodynamic responses of thiopental and propofol in different-aged patients
      during endotracheal intubation.
AB  - BACKGROUND: Thiopental and propofol are 2 popularly used anesthetic induction
      agents that have different pharmacological and pharmacokinetic actions. It is not
      clear how the hemodynamic responses differ in different-aged patients using these
      2 drugs for anesthetic induction. The aim of this study was to investigate the
      hemodynamic responses to propofol and thiopental of different-aged patients
      during endotracheal intubation. METHODS: Sixty patients, 20 to 83 years old, were
      included in this study. Patients were randomly divided into 6 groups according to
      age and different inductive anesthetics. Non-invasive blood pressure (NIBP)
      monitoring was performed every minute before anesthesia, during anesthetic
      induction with 5 mg.kg-1 thiopental or 2 mg.kg-1 propofol intravenously, and
      after intubation. RESULTS: Propofol induction produced a smaller mean arterial
      pressure increase immediately after intubation than did thiopental induction in
      adult and elderly groups (101.0 +/- 18.5 and 104.0 +/- 21.1 mmHg in the propofol
      groups vs. 138.3 +/- 17.1 and 138.9 +/- 16.1 mmHg in the thiopental groups at 1
      minute after intubation, p < 0.001 and p = 0.001, respectively). Differences in
      heart rate between propofol and thiopental groups were found in young and adult
      groups (85.1 +/- 9.2 and 81.7 +/- 10.9 in the propofol groups vs. 94.5 +/- 9.9
      and 95.0 +/- 14.0 beats per minute in the thiopental groups at 1 minute after
      intubation, p = 0.041 and p = 0.029, respectively). CONCLUSION: Propofol
      induction produced more stable hemodynamics after intubation in adult and elderly
      patients than did thiopental induction. Therefore, it is safer to use propofol
      for induction and intubation in adult and elderly patients.

PMID- 11512370
TI  - Craniopharyngioma involving supfrasellar region and sphenoid sinus: case report.
AB  - Craniopharyngiomas are benign, epithelial, slow-growing neoplasms that generally
      develop either in the suprasellar region or in both the suprasellar and
      intrasellar regions. They rarely occurs in the infrasellar region. Based on
      embryologic development of adenohypophysis, the tumor can arise along the path of
      the craniopharyngeal duct. We report on an 8- year-old boy who presented to us
      with headache and anorexia for several weeks during May 1999. Brain MRI revealed
      a huge sphenoid tumor. The tumor was completely excised by functional endoscopic
      sinus surgery on 12th August 1999. The postoperative course was smooth and no
      evidence of tumor recurrence was found on his latest follow-up visit in February,
      2000. From the clinical experience with this case, functional endoscopic sinus
      surgery is an alternative and a less-harmful surgical procedure for this kind of
      benign sphenoid tumor. Moreover, embryology development, epidemiology, clinical
      presentation, diagnostic method and treatment of craniopharyngioma are discussed.

PMID- 11512371
TI  - Laparoscopic diagnosis and management of Fitz-Hugh-Curtis syndrome: report of
      three cases.
AB  - Perihepatic adhesions between the liver capsule and the diaphragm or the anterior
      peritoneal surface characterizes Fitz-Hugh-Curtis syndrome (FHCS). FHCS is an
      extrapelvic manifestation of pelvic inflammatory disease and usually refractory
      to medical treatment and surgical intervention. With the increased incidence of
      pelvic inflammatory disease, chronic pelvic pain and sequalae of the process are
      becoming more common. Herein, we report 3 patients with pelvic inflammatory
      disease in whom medical treatment failed initially and FHCS was diagnosed via
      laparoscopy. Laparoscopic lysis of pelvic and perihepatic adhesions, irrigation
      of the abdomino-pelvic cavity, and antibiotics treatment after surgery
      successfully relieved these patients' symptoms. FHCS is not a new syndrome but
      most gynecologists might neglect this condition. Laparoscopy is a less invasive
      procedure than exploratory laparotomy. We recommend laparoscopy in patients with
      lower abdominal and right upper quadrant discomfort when other organic disease
      has been ruled out and medical treatment has failed to relieve symptoms.

PMID- 11512373
TI  - Spontaneous subconjunctival orbital fat prolapse: report of three cases.
AB  - Spontaneous subconjunctival orbital fat prolapse is an uncommon but benign
      entity. It is seldom discussed in the literature, and is sometimes confused with
      other ocular surface tumors, such as dermolipoma. We present 3 cases, two of
      which are bilateral, the other being unilateral. Two cases underwent surgical
      excision due to ocular irritation, and the pathology proved mature adipose tissue
      compatible with the diagnosis. Computed tomography (CT) was available for 1 case
      and revealed a fat-compatible radiolucent mass continuous with the intraconal
      fat. Some other reports have presumed that the intraconal fat was prolapsed from
      a dehiscence of Tenon's capsule. However, according to our surgical findings, we
      suggest that the possible weak point for intraconal orbital fat prolapse is
      between the regions where the rectus muscle tendons penetrate into Tenon's
      capsule. The fat just bulges anteriorly, but not penetrates the Tenon's capsule
      and the intermuscular septum.

PMID- 11512372
TI  - Carbon dioxide laser induced airway fire during larynx surgery: case report.
AB  - The precision intrinsic hemostatic properties of the laser have led to its wide
      use in modern clinical medicine especially in microscopic airway surgery.
      However, the intense heat generated by the high energy density of the surgical
      laser can convert combustible tubes into veritable torches, cause catastrophic
      fires, and result in severe injury to the patient. This is of particular
      importance when high energy is used on the continuous mode or when the
      endotracheal tube is repeatedly hit by the laser at the same spot. Most reported
      laser-induced complications result from the laser beam inadvertently falling on
      the areas that are not intended to be exposed. We report a case of a trans
      tracheostomy tube fire occurring during carbon dioxide (CO2) laser surgery.
      Aluminum-tape wrapping did not prevent this complication. It was found that the
      ignition of a trans-tracheostomy tube was caused by the laser striking an
      unprotected portion of the tube during resection of granuloma of the trachea.

PMID- 11512374
TI  - Human sleep EEG analysis using the correlation dimension.
AB  - Sleep electroencephalograms (EEG) were analyzed by non-linear analysis.
      Polysomnography (PSG) of nine healthy male subjects was analyzed and the
      correlation dimension (D2) was calculated. The D2 characterizes the dynamics of
      the sleep EEG, estimates the degrees of freedom, and describes the complexity of
      the signal. The mean D2 decreased from the awake stage to stages 1, 2, 3 and 4
      increased during rapid eye movement (REM) sleep. The D2 during each REM sleep
      stage were high and those during each slow wave sleep stage were low,
      respectively, for each sleep cycle. The mean D2 of the sleep EEG in the second
      half of the night was significantly higher than those in the first half of the
      night. Significant changes were also observed during sleep stage 2, but were not
      seen during REM sleep and sleep stages 3 and 4. The D2 may be a useful method in
      the analysis of the entire sleep EEG.

PMID- 11512375
TI  - Ultrafast frequencies: a new challenge for electroencephalography, with remarks
      on ultraslow frequencies.
AB  - EEG frequencies are not limited to the usual 0.5-70/sec (or 0.3-100/sec) range.
      In recent years, ultrafast activities between 100 and 1000/sec have been the
      topic of various studies with regard to physiological and paroxysmal conditions.
      Personal work on ultrafast frequencies in deep structures (elicited with
      pentylenetetrazol in rats) is mentioned in passing and will be the object of a
      special study. Other work focusing on the sensorimotor cortex and thalamocortical
      connections has proved to be seminal for ultrafast EEG research in conjunction
      with evoked responses (N20 response, SSEP) and experimental neurophysiological
      studies of afferent volleys, including those causing paroxysmal cortical
      responses. The well known decremental seizures with initially flat tracings
      require clarification with ultrafast recordings. In the physiological
      neurocognitive domain, Pfurtscheller's event-related desynchronization might also
      benefit from the use of ultrafast recording. A plea for additional ultraslow
      recording (DC recording) is also being made, since paroxysmal flattening
      (electrodecrement) may be associated with an ultraslow negative baseline
      deflection. The combination of ultrafast (facilitated by digital technique) and
      ultraslow (technically difficult in patients, easier in experimental animals)
      would finally denote the frequency-wise complete EEG.

PMID- 11512376
TI  - Decomposition of event-related brain potentials into multiple functional
      components using wavelet transform.
AB  - Event related brain potential (ERP) waveforms consist of several components
      extending in time, frequency and topographical space. Therefore, an efficient
      processing of data which involves the time, frequency and space features of the
      signal, may facilitate understanding the plausible connections among the
      functions, the anatomical structures and neurophysiological mechanisms of the
      brain. Wavelet transform (WT) is a powerful signal processing tool for extracting
      the ERP components occurring at different time and frequency spots. A technical
      explanation of WT in ERP processing and its four distinct applications are
      presented here. The first two applications aim to identify and localize the
      functional oddball ERP components in terms of certain wavelet coefficients in
      delta, theta and alpha bands in a topographical recording. The third application
      performs a similar characterization that involves a three stimulus paradigm. The
      fourth application is a single sweep ERP processing to detect the P300 in single
      trials. The last case is an extension of ERP component identification by
      combining the WT with a source localization technique. The aim is to localize the
      time-frequency components in three dimensional brain structure instead of the
      scalp surface. The time-frequency analysis using WT helps isolate and describe
      sequential and/or overlapping functional processes during ERP generation, and
      provides a possibility for studying these cognitive processes and following their
      dynamics in single trials during an experimental session.

PMID- 11512377
TI  - Wavelet transform of the EEG reveals differences in low and high gamma responses
      to elementary visual stimuli.
AB  - Multiunit electrophysiological studies indicate that oscillatory activity is
      common in the awake mammalian central nervous system. Synchronous 20-80 Hz
      oscillations, so called gamma rhythms, have been proposed as a possible
      fundamental physiological mechanism of binding neuronal activity underlying
      object recognition. The purpose of this study was to determine whether or not
      gamma band oscillatory activity in the human brain is modulated by attributes of
      elementary visual stimulation. The experiment was performed on 7 normal subjects.
      Sinusoidal gratings were presented over a range of spatial frequencies. Evoked
      potentials were recorded over 5 surface electrodes placed in a horizontal
      occipital chain across the back of the head. Discrete wavelet transform was
      performed on the first 200 msec following stimulus onset on the average data of
      256 sweeps. Power was analyzed with ANOVA across conditions. In our previous
      studies we have separated a "low" (14-28 Hz) and "high" (28-55 Hz) gamma band.
      The current results indicate that both gamma bands to full-field stimulation have
      the highest power at the midline (inion) electrode to a spatial frequency of 5.5
      cpd, which is the peak spatial frequency from foveal psychophysical data.
      However, the spatial frequency bandwidth is considerably narrower in the HG than
      in the LG band. Occipital spatial frequency tuning of the massed high gamma
      response is narrower than the tuning of individual cortical neurons. The
      bandwidth difference between low and high gamma band suggests that different
      frequency gamma range oscillations may represent not only different functional
      properties of visual processing, but may also reflect underlying differences in
      excitatory and postsynaptic inhibitory circuits shaping the contrast sensitivity
      of the human observer. Our study emphasizes the importance of elementary visual
      filter properties for gamma responses and the need to subdivide gamma frequency
      ranges according to functional properties.

PMID- 11512378
TI  - Stimulus- and frequency-specific oscillatory mass responses to visual stimulation
      in man.
AB  - Oscillatory mass responses centered at about 20-35 Hz or 100-120 Hz occur (after
      contrast or luminance visual stimulation, respectively) in the retina and cortex
      of animals and man and are recorded by electrical or magnetic methods. These
      oscillatory events reflect stimulus-related uni/multicellular oscillations of the
      firing rate/membrane potential and result from synchronization of neuronal
      assemblies selectively responding to the stimulus characteristics. Methodological
      problems in the study of these events derive from the contiguity in frequency
      between the ERG or VEP and the oscillatory responses and from the need to
      reliably define oscillatory events in time and frequency. Two methods (time
      frequency analysis by matching pursuit and locking index) have been implemented
      to approach this issue. Theory and application are reviewed.

PMID- 11512379
TI  - The processing of stereoscopic information in human visual cortex: psychophysical
      and electrophysiological evidence.
AB  - Three-dimensional depth perception relies in part on the binocular fusion of
      horizontally disparate stimuli presented to the left and right eye. The mammalian
      visual system offers a unique possibility to study electrophysiologically
      cortical neuronal mechanisms: since the input of the two eyes remains separated
      up to the level of the visual cortex, evoked potential components that are
      generated exclusively by cortical structures may be explored when dynamic random
      dot stereograms (dRDS) are presented. In a series of independent studies, we
      determined the scalp topography of dRDS evoked brain activity in different groups
      of healthy subjects, and we found consistent results. Major differences between
      stereoscopic and contrast evoked brain activity are seen in the strength of the
      potential fields as well as in their topography. Our findings suggest that there
      are fewer neurons in the human visual cortex that are responsive to horizontal
      disparity, and that higher visual areas like V2 are more engaged with
      stereoscopic processing than the primary visual cortex. On the other hand,
      component latencies of evoked brain activity show no effect signifying that the
      binocular information flow to the visual cortex has a similar time course for
      both the processing of contrast information and of dRDS stimuli. We could also
      verify that healthy subjects can learn to perceive 3D structure contained in
      dRDS. Changes in perceptual ability as measured with psychophysical tests are
      paralleled by systematic alterations in the topography of stereoscopically evoked
      potential fields. Stereoscopic VEP recordings may also be of clinical use: in
      patients with selectively disturbed depth perception but normal visual acuity
      there is a high correlation between clinical symptoms, perceptual deficiency, and
      altered VEP amplitudes and latencies.

PMID- 11512380
TI  - Auditory evoked responses to similar words with phonemic difference: comparison
      between children with good and poor reading scores.
AB  - Our previous study demonstrated a physiologic deficit in two-tone discrimination
      in poor readers. This was specific to the left parietal area suggesting that poor
      readers handled rapid tones differently. The current paper extends this finding
      in the same population, demonstrating that poor readers also have difficulty with
      phonemic discrimination. Long latency auditory evoked potentials (AEP) were
      formed using a phonemic discrimination task in a group of children with reading
      disabilities and controls. Measuring peak-to-peak amplitude of the waveforms, we
      found reduced N1-P2 amplitude in the Poor Reader group. Using the t-statistic
      significance probability map (SPM) technique, we also found a group difference,
      maximal over the mid-parietal area, from 584 msec to 626 msec after the stimulus
      onset. This difference was due to a lower amplitude on the Poor Reader group. We
      hypothesized that this late difference constitutes a P3 response and that the
      Poor Reader group generated smaller P3 waves. These auditory evoked response
      (AER) data support a discrimination deficit for close phonemes in the Poor Reader
      group as they had smaller N1-P2 absolute amplitude and developed smaller P3
      waves. Based on these data we should be able to differentiate between Good and
      Poor readers based on long latency potentials created from phonemic stimuli.

PMID- 11512381
TI  - Auditory evoked response data reduction by PCA: development of variables
      sensitive to reading disability.
AB  - Long latency auditory evoked responses (AER) were formed on 232 healthy normal
      and learning impaired subjects to tone pairs of 50 msec inter-stimulus interval
      (TALAER) and also to the words "tight" and "tyke" (TTAER). Both evoked potential
      (EP) type have been used to demonstrate differences between good readers (WIAT
      Basic Reading score > 115, N = 42) and poor readers (Reading score < 85, N = 42).
      A largely automated, hands off approach was used to reduce artifact
      contamination, to develop canonical measures for discriminating good from poor
      readers, and to predict reading scores across the entire population including
      intermediate (average) readers. Eye and muscle artifact were diminished by
      multiple regression. Substantial EP data reduction was enabled by an unrestricted
      use of Principal Components Analysis (PCA). For each EP type, 40 factors
      encompassed 70-80% of initial variance, a meaningful data reduction of about
      90:1. Factor interpretation was enhanced by mapping of the factor loadings. By
      discriminant analysis, resulting factors predicted reading group membership with
      over 80% jackknifed and also split--half replication accuracy. By multiple
      regression, they produced a canonical variate correlating significantly (p <
      0.001) with the Basic Reading score (r = 0.39). The TTAER factors were more
      useful than the TALAER factors. The relevance of rapid auditory processing and
      phonemic discrimination measurements to dyslexia is discussed.

PMID- 11512382
TI  - Real time human brain function: observations and inferences from single trial
      analysis of magnetoencephalographic signals.
AB  - This paper brings together results obtained by applying Magnetic Field Tomography
      (MFT) to the analysis of Magnetoencephalography (MEG) data over the last decade.
      It emphasizes the most recent developments where the availability of helmet-like
      MEG probes with well over 100 sensing coils provide a full coverage of the head.
      The paper shows that it is possible to extract tomographic information from
      single trial, millisecond by millisecond MEG signal, and demonstrates two ways
      that this capability can be exploited. First, the single trial reconstructions
      are used to obtain robust statistical measures of changes of activity over small
      latency windows. Second, the interaction between areas is studied by computing
      the mutual information between short, time-lagged sections of the single trial
      time-courses. The usefulness of the computationally demanding approach is
      demonstrated by analyzing experiments using two widely used protocols, one for
      face and affect recognition and the other for Contingent Magnetic Variation
      (CMV). The results show foci of significant changes of activity, which are
      consistent with what is reported in the literature and provide a deeper
      understanding of their significance. Some new, but not all that unexpected,
      findings also emerge from the analysis.

PMID- 11512383
TI  - [Oncology 2000].

PMID- 11512384
TI  - [Internet and oncology].

PMID- 11512385
TI  - [Ultrasonography-guided percutaneous alcohol injection for hepatocellular
      carcinoma in the cirrhotic patient].
AB  - The present study, performed in the Department of Internal Medicine and
      Gastroenterology of Policlinico of Modena, shows the results of the treatment
      with percutaneous ethanol injection of cirrhotic patients with hepatocellular
      carcinoma. In the period between June 1991-May 1998, 37 nodules of hepatocellular
      carcinoma, in 26 cirrhotic patients, were treated with ethanol injection under
      the ecographic guidance; the total number of sessions was 179. Ten lesions were
      recurrences (local or distant) in patients already treated. These patients were
      excluded from surgical treatment because of the high age, the high surgical risk
      or patient's choice. "Therapeutic success", defined as radiologic (TC or RM)
      demonstration of complete necrosis at the end of the first cycle of treatment,
      was achieved in 22/27 nodules after the first treatment (81.5%). Therapeutic
      success of the recurrence (second treatment) was achieved in 7/10 nodules (70%).
      In treated patients, survival probability (obtained with Kaplan Meier method) was
      84.5%, 73.0%, 50.0%, 38.5%, 26.9%, respectively at 1st, 2nd, 3rd, 4th and 5th
      year. After a total number of 179 sessions, there were no relevant complications.
      The results obtained in our experience prove the efficacy and safety of this
      therapeutic technique in patients with cirrhosis and hepatocellular carcinoma.

PMID- 11512386
TI  - [Paleobiology in the population of Herculaneum (79 A.D].
AB  - The anthropologic examination of the human skeletal remains recovered on the
      ancient beach of Herculaneum provides a unique opportunity for gaining
      paleobiological data on a Roman population. The eruption caught the people on the
      ancient beach as they were trying to escape; the volcanic surges and pyroclastic
      flows had different effects on them depending upon where they were on the beach.
      Those caught in the open suffered immediate dehydratation, with cranial explosion
      and complete burning of bones, whereas those trapped in the boat sheds suffered
      slower dehydration. Histological analysis of the bone remains reveals an exposure
      to temperatures of 350-400 degrees C; the slower dehydratation of those in the
      sheds resulted in the preservation of some soft tissues, which are exceptional
      findings.

PMID- 11512387
TI  - [Pinch-off syndrome and rupture of totally implanted venous access. Report of a
      case].
AB  - Permanently implanted central venous catheters (CVC) are very frequently used in
      the management of patients with cancer for the administration of chemotherapy,
      for infusing intravenous therapy or for total parenteral nutrition. Common
      complications in the use of CVC include venous thrombosis, infection, extrusion
      and occlusion. A potentially serious complication of implantable subclavian
      venous access devices is the "pinch-off" syndrome: the mechanical compression
      between the clavicle and first rib. The next stage of complication is catheter
      fracture, which is sometimes complicated with embolization. Repeated trauma to
      the catheter with mechanical compression between the clavicle and first rib has
      been postulated as the cause of fracture. Prompt retrieval should be attempted in
      all cases to prevent further complications. We reported a case.

PMID- 11512388
TI  - [Subacute cerebellar degeneration and pleural mesothelioma. Report of a case].
AB  - Subacute cerebellar degeneration is an autoimmune disorder and represents the
      paraneoplastic neurologic syndrome most frequently occurring in the central
      nervous system. To our knowledge, until now, no case of such a paraneoplastic
      syndrome as been described in patients with mesothelioma; on the contrary, some
      non-neurologic paraneoplastic syndromes have been described in patients with
      mesothelioma, and an aberrant production of cytokines has been suggested as the
      main pathogenetic event. In our report it can be supposed that an aberrant
      production of cytokines might have triggered an autoimmune reaction, causing anti
      Purkinje cells antibodies production, neurological damage and clinical outcome.

PMID- 11512389
TI  - [Chemotherapeutic management of peritoneal carcinomatosis].

PMID- 11512390
TI  - [Ablation of liver tumors with local radiofrequency hyperthermia].

PMID- 11512391
TI  - [Photodynamic treatment of tumors].

PMID- 11512392
TI  - [Effects of anemia and hypoxia on the course of tumors and the outcome of
      radiotherapy].
AB  - This paper will present an overview of the evidence that links anemia with a poor
      prognosis in a variety of human tumors treated with radiation, surgery,
      chemotherapy or combinations thereof. Hypoxia, acute or chronic in type, is also
      associated with a poor prognosis, mediated through two possible routes: 1)
      resistance to therapy with radiation or chemotherapy, and 2) the development of a
      more "aggressive" tumor phenotype. While anemia and hypoxia are related to some
      degree in some patients, it is probable that not all of the associated negative
      impact of anemia is translated through the hypoxia pathway. Because of the
      clinical importance and essential role hypoxia plays in tumor growth and
      treatment response, hypoxia and anemia are possible key targets for new
      therapies. The identified downstream molecular events resulting in increased
      glycolysis, erythropoiesis and angiogenesis form specific pathways which offer
      targets for inhibition. The relationship between anemia and hypoxia is complex
      and not clearly understood. Their relationships and the mechanisms by which they
      impact on treatment outcomes require further extensive investigations in both the
      clinic and laboratory.

PMID- 11512393
TI  - [Cerebral metastatis. Diagnostic and therapeutic features].
AB  - Brain metastases represent the most frequent intracranial neoplasms in adults:
      between 15 and 25% of patients with systemic tumors will face brain metastases
      along the clinical course of disease. Lung cancers, breast cancers and melanomas
      are the commonest causes of brain metastases (about 75%), while the primary site
      remains unknown inasmuch as 15% of cases. Headache, focal neurological deficits,
      epilepsy and intracranial hypertension are the most frequent initial symptoms and
      signs. Computerized Tomography and Magnetic Resonance represent the methods of
      choice for diagnosis. Supportive care is based on corticosteroids and
      antiepileptic drugs. Anticancer therapy planning must be based on prognostic
      factors: performance status, tumor activity and age. Surgical removal followed by
      external adjuvant radiotherapy is considered the best treatment in patients with
      single brain metastases and systemic disease under control or absent.
      Stereotactic radiosurgery is preferable in cases of unoperable metastatic lesions
      of the brain or progressive systemic disease. The usefulness of whole brain
      radiotherapy following surgery or radiosurgery is debated. In patients with
      multiple brain metastases, apart from radiotherapy, surgical excision of the
      symptomatic lesions, when feasible, seems advantageous. Chemotherapy is a valid
      option only in cases of metastases from chemosensitive neoplasms (small-cell lung
      tumors or breast tumors).

PMID- 11512394
TI  - [Bladder cancer].
AB  - OBJECTIVE: For optimum treatment planning and to establish the prognosis, the
      main objectives of diagnostic imaging techniques after detecting a tumor in the
      urinary bladder are to determine 1) its nature and histological structure, 2)
      depth of bladder wall invasion, 3) tumor localization and involvement of the
      ureter and trigone, 4) involvement of bladder wall lymphatics, and (5) to
      determine if there is or no regional and/or distant mestatasis. The capabilities
      of the diagnostic imaging techniques in regard to achieving the foregoing
      objectives are analyzed. METHODS: This study comprised 160 patients with a
      suspected or confirmed bladder tumor. The imaging methods utilized were:
      conventional radiology including IVP, retrograde and double contrast cystography,
      ultrasound, CT and MRI. RESULTS: Analysis of the images allowed assessment of 18
      morphological parameters, of which the following were among the most relevant:
      presence of ureterohydronephrosis, filling defect(s), tumor localization, tumor
      base, tumor-mucosa angle, wall stiffness, total wall thickness, changes observed
      in the perivesical space and degree of pelvic lymph node involvement.
      Visualization of a bladder filling defect confirms a bladder tumor. The
      predictors of the biological behaviour of bladder tumors, such as wall stiffness
      and lumen asymmetry, characteristically express tumor invasiveness. The tumor
      mucosa angles in relation to tumor base and peritumoral edema express a higher
      grade of infiltration for the obtuse angles and a lower grade for the acute
      angles. Determining tumor stage with accuracy is the essential challenge of the
      imaging methods in the assessment of bladder cancer. Both CT and MRI are used to
      analyze four basic aspects prior to treatment: 1) tumor appearance, 2) presence
      or absence of perivesical invasion, 3) presence or absence of invasion of the
      adjacent organs, and 4) presence or absence of lymphadenopathies. The accuracy of
      CT for tumor staging is estimated to be 88%-92% for stage D1 and 80%-85% for
      stages C and B2, respectively, while MRI has an accuracy of 95% for stage B2 and
      85% for tumor stages that compromise adjacent organs such as the prostate, uterus
      or vagina. CONCLUSIONS: Conventional radiological methods, together with
      transabdominal or transrectal ultrasound, have a high rate of accuracy for tumor
      detection. Determination of the stage of tumor invasion requires analysis of wall
      thickness, width of tumor base, tumor-mucosa angles and perivesical space. CT and
      MRI provide highly reliable diagnostic information on the foregoing. CT may
      present some difficulty in determining the stage of bladder wall invasion. With
      contrast enhancement, MRI has shown a greater capability to differentiate tumor
      stages B2 and C and is very similar to CT in detecting pelvic or retroperitoneal
      lymph node involvement.

PMID- 11512395
TI  - [Magnetic resonance of the male pelvis].
AB  - OBJECTIVE: To review the usage of magnetic resonance imaging (MRI) in the
      assessment of the male pelvis. METHODS: The applications of MRI in male pelvis
      pathology are reviewed. RESULTS/CONCLUSION: MRI has been demonstrated to be a
      useful diagnostic imaging technique in male pelvis pathology. It has been used
      mainly to evaluate the prostate, particularly for preoperative staging. MRI can
      depict tumor invasion of the capsule, periprostatic plexus, seminal vesicles,
      bladder, rectum and pelvic lymph nodes. Its main objective is to differentiate
      stages T1 and T2 of advanced disease. The endorectal coil enhances image
      resolution and diagnosis of extracapsular disease is more precise. MRI can also
      distinguish scar tissue from regional recurrence in patients submitted to radical
      prostatectomy. This imaging technique has also been used to assess benign lesions
      of the prostate and seminal vesicles; e.g., prostatic cysts, focal nodular
      hyperplasia, and amyloidosis of the bladder. Although ultrasound continues to be
      the primary noninvasive diagnostic method in the evaluation of scrotal pathology,
      MRI provides valuable diagnostic information in certain conditions; e.g.,
      testicular tumors, inflammatory processes, testicular torsion and trauma.

PMID- 11512396
TI  - [Magnetic resonance of the female pelvis].
AB  - OBJECTIVE: To analyze the utility of magnetic resonance imaging (MRI) in the
      assessment of the female pelvis, with special reference to the technical aspects.
      METHODS: Our experience and the literature on MRI in the evaluation of the female
      pelvis are reviewed. RESULTS/CONCLUSIONS: Conventional MRI assessment, which
      includes T1- and T2-weighted images in the axial, sagittal and coronal planes and
      T2 acquisitions along the major axis of the uterus in the sagittal plane, has
      proved effective in evaluating different pathologies of the female pelvis. MRI is
      particularly effective in staging endometrial carcinoma and in determining
      myometrial or cervical invasion. It is also useful in determining parametrial
      invasion in cervical carcinoma. In ovarian disease, MRI has been used in
      detecting peritoneal involvement, adenopathies and to characterize the lesion. It
      is particularly useful for planning the surgical approach in congenital disease.
      The high resolution of MRI with the use of the new coils has enhanced its
      efficiency and effectiveness in the diagnosis of congenital anomalies and tumors
      of the female urethra, and in the evaluation of prolapse of the urinary bladder
      and urinary incontinence.

PMID- 11512397
TI  - Variations in levator ani volume and geometry in women: the application of MR
      based 3D reconstruction in evaluating pelvic floor dysfunction.
AB  - OBJECTIVE: We report on the comparative 3-dimensional (3D) living female pelvic
      floor geometry in five women, comparing the volume, morphology, and integrity of
      the levator sling, and pelvic anatomic relationships among study subjects.
      METHODS: Five women of varying ages, parity, continence, and prolapse status were
      studied. Two-dimensional (2D) imaging of the pelvic floor organs was performed on
      each subject in the supine position. Manual segmentation techniques and solid
      modeling software was used to build 3D models of each patient's pelvic floor
      structures, which could then be viewed and measured on the computer screen. We
      measured levator muscle volume, posterior urethro-vesical angle, distance from
      the urethra to pubo-coccygeal line, and the levator plate angle. The integrity of
      pubo-coccygeal attachments was also recorded. RESULTS: Levator muscle volume
      ranged from 68 ml in the nulliparous female, to 26 ml in the grand multipara with
      severe prolapse and mild genuine stress incontinence (GSI). The second lowest
      volume (30 ml) was in the multipara with GSI. Volumes in the parous subjects
      without stress urinary incontinence or pelvic organ prolapse were 36 and 39 ml.
      Pubo-coccygeal attachments were found to be torn in the 2 symptomatic subjects,
      and were intact in all 3 asymptomatic subjects. CONCLUSION: MR based 3D modeling
      is feasible and can be used in a research setting to evaluate complex anatomic
      relationships which may accompany pelvic floor dysfunction. The technique can
      also be used to evaluate levator muscle morphology and volume, as well as pelvic
      floor support integrity and its possible role in GSI and prolapse. We are
      currently conducting a larger study to validate our technique, and to better
      define the relationship between pelvic floor geometry and pelvic floor
      dysfunction.

PMID- 11512398
TI  - [Renal cancer].
AB  - OBJECTIVES: This study was carried out 1) to analyze the growth and clinical
      manifestations of renal adenocarcinoma; 2) to determine the presence of tumor,
      its malignant nature, size, local extent or distant spread and route of
      dissemination according to the imaging methods utilized, and 3) to determine the
      accuracy of the different imaging procedures, such as IVP, US, CT, and MRI, in
      staging renal adenocarcinoma. These objectives attempted to provide answers to
      the following questions: a) Are there currently substantial changes in the
      biological behavior of renal adenocarcinoma?, b) Does the route of tumor
      dissemination (direct infiltration through the capsule, lymphohematogenous,
      cancer embolus carried by the bloodstream to a distant location) affect the rate
      of progression to stages III and IV?, and c) What are the most relevant findings
      of the imaging methods that aid in determining the extent of the renal tumor?
      METHODS: 106 renal masses were evaluated; of these, 93 were renal
      adenocarcinomas. The diagnosis, clinical evaluation and preoperative staging were
      based on the clinical history, physical examination, symptoms and imaging methods
      (IVP, US, CT, and MRI) to assess renal morphological changes, presence of
      calcifications, mass effect, tumor mass ultrasound characteristics, densitometry
      or MR signal pattern, perinephric fat involvement, venous vasculature,
      involvement of renal fascia, locoregional lymph nodes or metastasis and distant
      neoplastic changes. RESULTS: A third of the tumors had a size greater than 10 cms
      and practically half were 5-10 cms in size. Calcifications were found in 47%; 85%
      were punctiform and showed a central location. 88% of the tumors showed areas of
      necrosis. Due to the presence, in most of the cases, of a viable tumor, necrosis,
      calcification or cystic degeneration, the adenocarcinomas showed a very
      inhomogeneous ultrasound pattern and with varying degrees of vascularization on
      CT volumetric assessment. Invasion of perinephric fat and tumor fibrous septae
      were found in 65% on CT evaluation, although MRI was particularly sensitive in
      detecting fat infiltration in the early stages of perinephric involvement, venous
      thrombosis, involvement of adjacent and distant organs and tumor hemorrhagic
      changes. CONCLUSIONS: In determining the biological behaviour of renal
      adenocarcinoma, preoperative staging of infiltration and prognosis, US,
      volumetric CT and MRI are currently the diagnostic methods with the highest
      accuracy, specificity and sensitivity. These diagnostic methods allow early
      detection of tumors thereby making them potentially curable. Lymphatic drainage
      of the tumor may be determinant in its more or less rapid progression from Robson
      stage II to IIIa and IIIb, and thereafter to stage IV. CT and MRI showed a higher
      accuracy for tumor detection, localization, determining local extent, tumor
      characterization and staging. Detection of a tumor pseudocapsule comprised of
      reactive fibrous tissue and compact renal parenchyma by CT or MRI allows
      determination of the borders of the renal tumor. Lymph node involvement radically
      changes the prognosis and survival in renal adenocarcinoma.

PMID- 11512399
TI  - [Renal magnetic resonance].
AB  - OBJECTIVES: To establish the role of MRI in renal disease, its indications,
      advantages and disadvantages. To briefly describe the main MRI techniques and
      renal features depicted on MRI before and after administration of a contrast
      agent, and present the MRI findings in different renal conditions. METHODS: The
      images were obtained with the GE MR 0, 5 T. T1- and T2-weighted spin echo and
      echo gradient sequences were utilized according to the protocol described in the
      article. RESULTS/CONCLUSIONS: MRI is very useful in the study of renal disease
      due to its high spatial resolution. Its cost, and because it is not widely
      available, have limited the indications of MRI to those cases whose diagnosis
      cannot be established by other imaging techniques (US and CT) and patients in
      whom iodated contrast material (i.e., allergy to iodine or renal failure) or
      ionizing radiation (i.e., pregnancy) is contraindicated. MR has a high diagnostic
      reliability in the evaluation of the extent of the renal tumors. MR angiography
      and MR urography permit adequate and non-invasive assessment of the vascular and
      collecting systems without the need to utilize iodated contrast agents.

PMID- 11512400
TI  - [MR in renal masses].
AB  - OBJECTIVE: To review the utility of MR imaging in the assessment of renal masses,
      with special reference to the morphological characteristics of the different
      tumor types. Staging of renal cell carcinoma is also discussed. METHODS: The
      literature on the use of MRI in the evaluation of renal masses is reviewed. The
      technical aspects and the indications of MR urography are discussed and compared
      with those of other imaging techniques. RESULTS/CONCLUSIONS: MRI permits
      multiplanar analysis and facilitates detection and characterization of lesions.
      Furthermore, it allows clear depiction of the relationships of the tumor and the
      adjacent structures for efficient surgical planning.

PMID- 11512401
TI  - [Small renal mass. Diagnostic management].
AB  - OBJECTIVE: The detection of renal masses < 3 cm has continually increased over
      the last few years due to the improvements and wide use of imaging techniques
      that have made early diagnosis of renal carcinoma possible and therefore to
      directly influence patient survival. The approach to small renal lesions based on
      our experience and the data published in the literature are analyzed.
      METHODS/RESULTS: The small renal lesion is problematic and indeterminate because
      of its size, which makes it difficult to measure its density before and after
      contrast administration on CT assessment, and is the main diagnostic factor in
      this disease. Small renal masses constitute a diagnostic challenge whose
      resolution may lead to disproportionate surgery. This has led us to utilize
      multiphasic helical CT with specific protocols and to look for data in the
      natural history of the renal tumor to complement the radiological findings.
      Series have been published that demonstrate that the slow growth and degree of
      malignancy of small renal tumors warrant a regular helical CT control evaluation
      because it allows comparison of the findings and detects growths > 1 cm, which is
      a sign of malignancy and consequently an indication for surgery. CONCLUSION: Due
      to the natural course of small renal tumors and the reproducibility of
      multiphasic CT, the correct approach is to perform close follow-up of patients at
      surgical risk or with an equivocal diagnosis using this imaging technique.

PMID- 11512402
TI  - [Computerized tomography angiography of the renal vessels].
AB  - OBJECTIVE: To present the findings and discuss the diagnostic possibilities of
      helical CT angiography and digital substraction angiography, and to compare their
      capabilities to depict renal vascular anatomy (arterial and venous) and the
      pathological changes. METHODS: The findings obtained by the different imaging
      modalities of CT angiography were compared with those of digital substraction
      angiography in more than 2000 studies performed at our hospital. RESULTS:
      Agreement and correlation between CT angiography and digital substraction
      angiography, the gold standard, were found in the vast majority of the cases. In
      conjunction, various image post-processing possibilities of CT angiography
      achieved almost 100% sensitivity and specificity. CONCLUSION: CT angiography is
      capable of obtaining results that overlap with those of optimum quality digital
      substraction angiography and is a less invasive and less costly procedure. The
      time required is shorter and the radiation dose exposure is markedly lower for
      patient and staff. Helical CT is a minimal invasive technique with an increasing
      role in the evaluation of the renal vessels. Although its field of applications
      has not yet been completely established, it is less invasive, less costly,
      radiation exposure of patient and staff performing the procedure is lower, and
      has had a considerable impact in the diagnosis and management of vascular
      disorders. CT angiography is applicable to a number of indications of
      conventional angiography and has permitted vascular screening studies where one
      would be reluctant to indicate catheter arteriography. This imaging procedure is
      mainly used for 1) screening of patients that may have renovascular hypertension
      that may be amenable to surgical or intraluminal treatment; 2) follow-up of
      treated patients; 3) preoperative assessment of kidney donors; 4) evaluation of
      renal artery aneurysms (uncommon), aneurysms extending to the renal arteries or
      dissection of the aorta. It is also effective, but only slightly superior to
      conventional CT, in depicting thrombosis or tumor invasion of renal veins,
      although it is highly effective in evaluating anatomical variations and renal
      vein anomalies. In inflammatory vascular disease it is similar to catheter
      angiography, although its impact is not considerable due to the low prevalence of
      inflammatory vascular disease in our setting.

PMID- 11512403
TI  - [Assessment of erectile dysfunction with Doppler-duplex ultrasonography].
AB  - OBJECTIVE: To evaluate the penile echo Doppler study and review the anatomy,
      perfusion, innervation and physiology of erection. METHODS: The technique,
      spectral morphological changes of the cavernous arteries after drug-induced
      erection, modifications and normal values are described. RESULTS/CONCLUSION:
      Impotence or erectile dysfunction, which is defined as the inability of the male
      to achieve or sustain an erection sufficient for successful sexual intercourse,
      is a benign condition with an important impact on the wellbeing of the patient.
      Statistical studies have shown a high age-dependent prevalence in healthy
      subjects and an association with different conditions in patients. To establish
      whether impotence is organic or not and to identify its underlying cause require
      submitting the patient to not a few diagnostic tests. Since most of the cases of
      organic impotence are of vascular origin, it is necessary to utilize a diagnostic
      method that can identify patients with an underlying vascular disorder (the most
      common cause) and distinguish those with arteriogenic impotence from those with
      insufficiency of the complex corporeal veno-occlusive system.

PMID- 11512404
TI  - [Ureteral stenosis and pneumatic dilatation].
AB  - OBJECTIVE: To determine the efficacy of balloon dilatation in the treatment of
      ureteral strictures and analyze the outcome according to its etiology. METHODS:
      77 ureteral dilatations were performed in 74 patients. Most of the strictures
      were postoperative sequelae and the other cases were due to chronic inflammatory
      conditions. RESULTS: The overall success rate was 47%, partial improvement was
      achieved in 17% and the failure rate was 36%. In our series, the postoperative
      strictures responded slightly better to balloon dilatation than those arising
      from chronic inflammatory conditions. CONCLUSION: Endourologic techniques based
      on the percutaneous methods of interventional radiology have reduced the usage of
      invasive conventional surgery in the treatment of strictures. Although the
      proportion of unsatisfactory results is not negligible, balloon dilatation should
      be the first treatment option for ureteral strictures because it is less
      invasive, carries a low morbidity and requires a shorter hospitalization. If the
      results are unsatisfactory, re-dilatation can be attempted or conventional open
      surgery can be performed.

PMID- 11512405
TI  - [Nephrourology and nuclear medicine today].
AB  - OBJECTIVE: To review the radioisotope studies in Nephrourology that are
      frequently performed in the Nuclear Medicine Department, their clinical
      applications and diagnostic yield. METHODS/RESULTS: Radionuclide studies in
      Nephrourology allow evaluation of different aspects of renal function after
      intravenous injection of radioisotopes by blood volume/time (ml/min) measurements
      (glomerular filtration rate, effective renal plasma flow) or visualization in the
      form of images or graphic display (renal scintigraphy, sequential study,
      renography) that permit determination of the differential renal function. A
      sequential study, diuresis renography or angiotensin converting enzyme (ACE)
      inhibitor renography can be performed to evaluate the changes in renal function
      induced by the diuretics or ACE inhibitors. Radionuclide cystography permits
      detecting vesicoureteric reflux. These radioisotope studies are commonly utilized
      in detecting reflux nephropathy and renal scarring (renal scintigraphy and
      radionuclide cystography), obstructive nephropathy (diuresis renography),
      renovascular hypertension (ACE inhibitor renography) and in evaluating renal
      transplantation (sequential study, renography, diuresis renography and ACE
      inhibitor renography). CONCLUSION: Radionuclide studies have different
      applications in Nephrourology, some of which are considered to be diagnostic gold
      standards, such as renal scintigraphy with DMSA to detect cortical anomalies, ACE
      inhibitor renography to identify hypertensive patients that will not benefit from
      revascularization surgery and to determine the glomerular filtration rate. Other
      studies, such as diuretic renography, are not considered to be gold standards due
      to the lack of standardized protocols.

PMID- 11512406
TI  - [Positron emission tomography (PET): application in urogenital system oncologic
      diseases].
AB  - OBJECTIVE: To review and discuss the applications of positron emission tomography
      (PET), with special reference to genitourinary tumors. METHODS: Our experience
      and the relevant literature on PET are reviewed. The principles and technical
      aspects of PET, the different parameters analyzed, its clinical indications,
      applications in genitourinary tumors and research are discussed.
      RESULTS/CONCLUSION: Positron emission tomography (PET) permits visualization and
      determination in vivo of a number of tissue and organ physiologic and
      biomolecular parameters. PET is also used for biomedical research and is
      especially useful for research and development of new drugs, tumor biomolecular
      phenotyping and for monitoring gene therapy. It has also proved to be a useful
      non-invasive diagnostic imaging technique in the clinical setting with an
      excellent cost-effectiveness in cancer patients. Fluor-deoxyglucose-F18 or FDG is
      the only radiotracer with a clinical application. PET detects the intense tumor
      uptake of FDG due to the higher glycolytic index of tumor cells. The PET
      tomograms allow performing a complete study of the whole body in the same
      session. The clinical indications of FDG PET that are currently accepted and
      established are: diagnosis of benign versus malignant solitary lung nodule, pre
      treatment study to determine the extent of non-small cell lung cancer,
      localization and re-staging of colorectal cancer recurrence, extent and post
      treatment assessment of lymphomas and extent of recurrent malignant melanoma. The
      application of FDG PET in genitourinary cancer is controversial. It does not
      appear to be useful in the initial diagnosis of primary prostatic, bladder and
      kidney tumors. Its clinical yield appears to be better for localizing recurrence
      and re-staging patients with increased prostatic specific antigen (PSA) levels
      after treatment of a primary prostatic tumor. Furthermore, it can also be used to
      determine the extent of hypernephroma and malignant bladder tumor suspected to be
      metastatic at the initial diagnosis. In testicular germ cell tumors, FDG PET can
      be a very useful tool for pre-treatment staging and to evaluate post-treatment
      residual masses.

PMID- 11512407
TI  - Postural stability and fractal dynamics.
AB  - Methods of non-linear dynamics and deterministic chaos may provide us with
      effective quantitative descriptors of the dynamics of postural control. The goal
      of this study was to introduce a new measure, which would allow to determine the
      fractal structure of posturographic signals and to measure the effect of the loss
      of visual feedback information in postural control. The results of the study show
      that fractal dimension (Df) is a very useful, reliable and sensitive measure of
      the complexity of posturographic signals. Therefore Df can be used for the
      evaluation of postural stability and its changes due to pathology or an age
      related decline.

PMID- 11512408
TI  - Sphingolipid derivatives modulate intracellular Ca2+ in rat synaptosomes.
AB  - Sphingosylphosphorylcholine (SPC) induces a rapid increase of intracellular Ca2+
      concentration in isolated synaptosomes. This effect is dose-dependent and is also
      dependent on extracellular Ca2+. Sphingosine (SPH) has a smaller effect and
      treatment with psychosine (PSY) is ineffective, which suggests that
      phosphorylation of the 1-carbon of SPH is required for the SPC to act as a Ca2+
      release agonist in synaptosomes. Experiments performed in the presence of heparin
      or ryanodine indicate that SPC-elicited Ca2+ release is not mediated by IP3 or
      ryanodine receptors. Finally, our results show that the effect of SPC on Ca2+
      concentration is nimodipine-sensitive, suggesting that SPC possibly activates a
      specific sphingolipid-gated Ca2+ channel in synaptosomes.

PMID- 11512409
TI  - Tetanic depression: a phenomenon influencing the production of tension in fast
      twitch motor units in rat medial gastrocnemius.
AB  - The influence of an increase or a decrease in the stimulation frequency on
      tension development during a tetanus was studied in motor units of the rat medial
      gastrocnemius muscle. These effects were tested in one tetanus evoked at two
      frequencies of stimulation, a lower immediately followed by a higher one or the
      reverse. For all fast motor units it was observed that after the first part of a
      tetanus at a lower frequency of stimulation the tension of the following part, of
      the better fused contraction, was depressed. This effect was called a tetanic
      depression. When the lower stimulation frequency was followed by the higher one,
      the depression was visible in some motor units only whereas in the remaining
      units a potentiation of the second part of the tetanus was visible. The tetanic
      depression was larger in fast resistant than in fast fatigable motor units. In
      slow motor units tetanic depression was not observed. The tetanic depression is a
      phenomenon which can influence the production of contractile tension by fast
      motor units.

PMID- 11512410
TI  - Effect of posterior hypothalamic injection of procaine on the hippocampal theta
      rhythm in freely moving cats.
AB  - Earlier in vivo studies conducted on freely moving and anesthetized rats
      demonstrated that the posterior hypothalamus (PH) comprises pathways critical for
      producing the synchronous hippocampal formation (HPC) theta rhythm. In addition,
      these findings suggested that the frequency of the HPC theta was encoded in the
      PH and then was fed via the medial forebrain bundle to the medial septum and HPC.
      In the present study we attempted to verify this hypothesis with use of a
      different in vivo model--freely moving cats. The microinjection of the local
      anaesthetic, procaine, into the PH region reversibly suppressed the spontaneous
      as well as sensory and electrically induced HPC theta. However, in contrast to
      rats, in freely moving cats microinjection of procaine into the PH reduced the
      amplitude of the HPC theta but had no effect on theta frequency. We conclude that
      in freely moving cats the PH region comprises a critical part of the ascending
      brainstem pathway, for production of the HPC theta rhythm. In contrast to rats,
      in freely moving cats ascending inputs from the brainstem to the PH contribute
      mainly to the amplitude of the HPC theta rhythm.

PMID- 11512411
TI  - Sex difference in rabbit eyelid conditioning.
AB  - The rabbit eyelid conditioned reflex has been used to compare associative
      learning in males and ovariectomized females. A new method for monitoring eyelid
      movements is described. Rabbits were trained on simple delay classical
      conditioning. Conditioned responses were recorded during 8 acquisition days and 6
      days of extinction training. Analysis of variance (ANOVA) and the least
      significant difference (LSD) post hoc test was used to analyze the data. The
      results showed that males achieved significantly better learning than females
      during the first day of acquisition but later they slowly attained the best
      result, contrary to females. Moreover, extinction of the conditioned reflex was
      significantly faster in females than in males. It is postulated that females
      learn and extinguish faster than males because of a higher level of brain
      plasticity.

PMID- 11512412
TI  - MR imaging of seven presumed cases of central pontine and extrapontine
      myelinolysis.
AB  - MRI was performed in seven patients with presumed central pontine and
      extrapontine myelinolysis. The underlying diseases were diabetes, lung cancer,
      Wilson disease, trauma, alcoholism, renal insufficiency and hemodialysis. CPM was
      found in four cases (in two of them extrapontine lesions were considered as
      resulting from Wilson disease), CPM and EPM in three patients. The localization
      of extrapontine changes included cerebellum, cerebral peduncles, caudate and
      lentiform nuclei, internal capsules, white matter and cortex of the cerebrum.

PMID- 11512413
TI  - Application of infrared detection in the recording of eyelid movements in
      rabbits.
AB  - Classical conditioning of the eyelid reflex has been used for a long time to
      study associative learning in animals and humans. A new experimental procedure
      for rabbit's eyelid conditioning was constructed and described. A phonopneumatic
      stimulator generated conditioned and unconditioned stimuli and a photoelectric
      transducer acting in close infrared converted movements of rabbits' eyelid to
      electric signals. An example of acquisition and extinction training is
      illustrated. This method of eyelid movement monitoring is noninvasive. It may be
      useful for chronic studies of learning processes in rabbits when used with
      headpieces for microdialysis probes, electrodes or cannulas which could be
      implanted into brain structures.

PMID- 11512414
TI  - The influence of lidocaine on the permeability of the blood-cerebrospinal fluid
      barrier in experimental acute hypercapnia in the rabbit.
AB  - In a previous study we have provided evidence, that acute experimental
      hypercapnia due to hypoventilation in the rabbit alters blood-cerebrospinal fluid
      barrier function in the brain (Pakulski et al. 1998). The purpose of this study
      therefore was to determine if lidocaine would prevent the observed alterations in
      the blood-cerebrospinal fluid barrier function. The experiments were conducted in
      16 adult Chinchilla rabbits submitted to acute hypercapnia due to mechanical
      hypoventilation (PaCO2 between 8-9.5 kPa over 180 minutes) under pentobarbital
      anaesthesia. The studied group (n = 8) was treated by lidocaine infusion 10 mg kg
      1 h-1. After 180 minutes of hypercapnia the value of cerebrospinal fluid-blood
      index of gentamycin concentration, indicating the permeability of the blood
      cerebrospinal fluid barrier, was significantly lower in animals treated with
      lidocaine (4.03 +/- 2.32 vs. 19.05 +/- 5.49; P < 0.01). We conclude that
      lidocaine may attenuate the increase of blood-cerebrospinal fluid barrier
      permeability under conditions of experimental acute hypercapnia lasting 180
      minutes in the mechanically ventilated rabbit.

PMID- 11512415
TI  - Effects of light and darkness on cell deaths in damaged retinal ganglion cells of
      the carp retina.
AB  - Effects of light and darkness on the apoptosis of retinal ganglion cells (RGCs)
      in young carp were measured by TUNEL method after transection of the optic nerve.
      Following the operation, the fish were kept under one of four regimens; constant
      darkness (DD), constant light (LL), 12 hr light and 12 hr dark (LD) and 3 hr of
      flickering light followed by 21 hr in the dark (FL). On day 3, the highest ratio
      of apoptotic RGCs was seen under conditions of DD, followed by LL, LD, and FL. On
      day 6, the percentages of apoptotic RGCs were lower under every experimental
      condition than what they had been earlier on day 3, but the same ranking order
      was maintained. Immunohistochemically it could be shown that phosphorylated ERKs
      were more intensively localized in FL rather than DD retinas. The results suggest
      that illumination regimens, and in particular cyclic diurnal light/dark changes,
      have an influence on the degree of apoptosis of damaged RGCs, and that inhibition
      of apoptosis is correlated with the higher expression of phosphorylated ERKs.

PMID- 11512416
TI  - Interactions between P300 and passive probe responses differ in different visual
      cortical areas.
AB  - The regulation of firing thresholds of cortical neurons was suggested as one of
      the mechanisms underlying the generation of the P300 component in the human event
      related potential. According to this hypothesis, the detection of an important
      stimulus produced the widespread inhibition of "irrelevant" networks,
      interrupting their ongoing activity and facilitating the analysis of selected
      information. In the present experiment, the responsiveness of visual cortex was
      evaluated during the P300 potential by using additional, probing stimuli. Large
      separation of the cortical visual fields permitted separate analysis of the input
      and more advanced stages of processing. Responses were recorded from Fz, Cz, Pz
      and Oz scalp sites. P300 waves were evoked by visual, mentally counted stimuli in
      a standard "odd-ball" procedure. Visual probes were delivered 200, 300, 400, 500,
      700 and 1000 ms later. No responses to the probes were required. Significant
      suppression of responses to the probes delivered less than 400 ms after target
      stimuli was found in Oz and Pz but not in Cz or Fz. The suppression was not
      proportional to the voltage levels from which probe responses started. In Fz and
      Cz, latencies of probe responses were elongated if probes were delivered less
      than 400 ms after target stimuli. The results suggest that probe responses
      suppressed by the P300 potential in occipital and parietal cortex may be restored
      in frontal areas. In these areas the P300 potential could delay probe responses
      instead of suppressing them.

PMID- 11512417
TI  - [Hyperactive behavior in adults; possibly attention deficit/hyperactivity
      disorder (ADHD)].
AB  - Two men aged 34 and 41 years, respectively, displayed hyperactive and chaotic
      behaviour. On the basis of the symptoms and their effect on the patients'
      functioning during childhood and adulthood, the diagnosis of attention
      deficit/hyperactivity disorder (ADHD) was made. The patients became calmer with
      methylphenidate treatment, but a few months later they chose to stop taking the
      medication and to accept their hyperactive behaviour. To establish the diagnosis
      of ADHD in adults, it is essential that some of the symptoms started before seven
      years of age and that the symptoms and resulting impairment persist over time
      from childhood into adulthood. To investigate this, it is necessary to obtain
      heteroanamnestic information from the parents or other people who knew the
      patient at that age. Treatment with medication and psychoeducation is effective
      and can prevent further suffering.

PMID- 11512418
TI  - [Discussion of attention deficit-hyperactivity disorder (ADHD): facts, opinions
      and emotions].
AB  - Critics of the concept of attention deficit/hyperactivity disorder (ADHD) claim
      that it is not a clear-cut psychiatric disorder, but rather a social stigma
      attached to a child that is difficult to handle. The counter-argument to this
      view is that ADHD is a descriptive diagnosis in which indices of the severity of
      behaviour enable it to be distinguished from normal behaviour. Both over
      diagnosis and under-diagnosis occur. Treatment with medications is criticised on
      the basis that it is an inadequate replacement for good parenting and education,
      that it medicalises a psychosocial problem but does not cure it, and that the
      long-term effects of this approach have not been proven. Those in favour of
      medical treatment claim that medication and efforts to improve parenting and
      education are not counter-effective, but that they complement each other.
      Medication is an important contributory factor in the proper care of ADHD
      patients. Treatment with psychostimulants is criticised on the basis that the
      extent of the side-effects are underestimated, and that there is a risk of
      addiction. However, proponents of this approach claim that, if used correctly,
      the unpleasant side-effects only occur in a small minority of children.

PMID- 11512420
TI  - [Therapies for smoking cessation (antidepressants, nicotine-replacement and
      counseling) and implications for the treatment of patients with chronic
      obstructive pulmonary disease].
AB  - Only a small percentage of smokers who state they want to stop smoking in the
      next half year, succeed in doing so. This is not only due to the addictive nature
      of smoking cigarettes, but also because of psychological and social factors.
      Approximately 80% of the people who have used nicotine-replacement therapy return
      to smoking after some time. Therefore, the interest in non-nicotine
      pharmacotherapy has increased considerably in recent years. The antidepressants
      bupropion and nortriptyline are, compared to a placebo, particularly effective
      smoking cessation aids (relative risk (RR)nortriptyline: 2.7; 95% CI: 1.3-5.3;
      RRbupropion: 1.5; 95% CI: 1.1-2.6). A combined strategy of nicotine-replacement
      therapy with counselling or antidepressants (bupropion or nortriptyline) with
      counselling, in which the physiological as well as the psychological aspects of
      smoking cessation are treated, seems to be the most effective. Although smoking
      cessation is seen as the single most important way of preventing a further
      deterioration of the lung function at all stages of chronic obstructive pulmonary
      disease (COPD), little research has been conducted amongst COPD patients.
      Especially the use of the antidepressants bupropion or nortriptyline seems
      particularly interesting for the treatment of patients with COPD. This is not
      only because smoking cigarettes is the major risk factor for the development of
      the disease, but also because COPD patients have a higher than normal prevalence
      of depression. Furthermore, an association has been found between smoking
      cigarettes and depression, and the presence of depression or depressive symptoms
      appears to be an important cause of relapse.

PMID- 11512419
TI  - [Uneasiness about the safety of bupropion as an aid to smoking cessation
      unjustified ].
AB  - A report in a national newspaper on Thursday 26 April 2001, linked the anti
      smoking drug bupropion to 41 deaths. From the reports of suspected adverse
      reactions received by the Netherlands Pharmacovigilance Foundation, it appears
      that more than half the cases concerned patients at risk of developing smoking
      related diseases. In 15 cases, the simultaneous use of bupropion and another
      antidepressant (10 patients), theophylline (1 patient) or insulin (4 patients)
      was reported, even though these combinations may lead to an increase in the risk
      of seizures. Furthermore, 2 patients were reported to have been taking anti
      epileptics, despite the fact that use of bupropion is contra-indicated in
      patients with a seizure disorder. The results seem to illustrate that the
      guidelines described in the product information are not being adhered to in all
      cases. Provided that bupropion is used according to the guidelines in the product
      information, this new aid in smoking cessation is considered an effective and
      safe drug. It is highly unlikely that bupropion has contributed to any deaths. If
      prescribed appropriately and in combination with counselling (e.g. minimal
      intervention strategy), bupropion is as yet the most effective aid in helping
      people stop smoking.

PMID- 11512421
TI  - [Diagnostic image (49). Megaesophagus in achalasia].
AB  - Already as a child a 49-year-old man suffered from cough, regurgitation and
      dysfagia. He had a mega-esophagus, caused by achalasia. He was successfully
      treated by resection of the esophagus and intrathoracic gastric bypass.

PMID- 11512422
TI  - [Functioning, comorbidity and treatment of 141 adults with attention deficit
      hyperactivity disorder (ADHD) at a psychiatric outpatient department].
AB  - OBJECTIVE: To describe the functioning, comorbidity and treatment of adults with
      attention deficit hyperactivity disorder (ADHD). DESIGN: Retrospective. METHOD:
      In the period 1 May 1995 to 31 January 1998, 141 patients aged 18-54 were
      diagnosed with ADHD at the Delfland Psychiatric Outpatients' Department, Delft,
      the Netherlands. For all of these patients, data concerning the functioning,
      comorbidity, and the response to treatment with clonidine (n = 34) or
      methylphenidate (n = 99), were collected from anamneses, hetero-anamneses and
      school reports. RESULTS: The most frequent complaints were: mood-swings, rage
      outbursts, sensation-seeking behaviour, sleeping disorders, anxiety and
      depressive symptoms. In 94% (n = 123) of the cases, childhood onset of ADHD
      symptoms was confirmed by a family member. The distribution of ADHD subtypes was
      comparable to the distribution in children. Psychiatric comorbidity was common.
      Treatment with methylphenidate was more effective and better tolerated than
      treatment with clonidine. CONCLUSION: With respect to ADHD subtypes, patterns of
      comorbidity and effectiveness of medication, ADHD in the adults studied was
      comparable with what is known about ADHD in children.

PMID- 11512423
TI  - [An infant with pain and meningeal irritation due to Guillain-Barre syndrome].
AB  - In a five-month-old girl, who for a week had cried and displayed a relapse in the
      motor development, generalised hypotonia and meningism were found. Eventually,
      the results of the cerebrospinal fluid analysis and electromyography indicated
      Guillain-Barre syndrome. She was treated with immunoglobulins and made a quick
      recovery. Guillain-Barre syndrome is an acute or subacute inflammatory
      demyelinating polyradiculoneuropathy that can occur at any age. In children, the
      classic symptoms such as a flaccid paralysis and areflexia are not always
      predominant. Instead, pain is often the most prominent symptom, along with
      meningism. These symptoms are often insufficiently recognised in practice and as
      a result of this, delays in the diagnosis of this potentially life-threatening
      disease often occur.

PMID- 11512424
TI  - [Treatment of pain in cancer with systemically administered opioids].

PMID- 11512425
TI  - [Ventricular fibrillation: daily, possibly leading to embolization in an
      extremity].

PMID- 11512426
TI  - John Martyn Harlow: "Obscure country physician"?
AB  - If John Martyn Harlow is known at all in the neurosciences, it is because he was
      the physician who attended Phineas Gage and followed up his case. Although
      Harlow's brief but insightful accounts of the changes in Gage's personality are
      fairly well recognized, and his skill in treating Gage often acknowledged, Harlow
      himself is, for the most part, the shadowy figure caught by the self-depreciatory
      characterization of the subtitle of this paper. Although his contribution to the
      neurosciences was singular, literally and figuratively, he deserves a place in
      the history of the subject. Harlow's training in antiphlogistic therapy can be
      seen in his treatment of Gage and in his evaluation of its results. As a medical
      student, he was also exposed to phrenological doctrine, the influence of which
      can also be seen in his appreciation and explanation of some aspects of Gage's
      behaviour. Manuscript materials, newspaper reports, and other little known
      material are used here to evaluate Harlow's contributions to medicine and to the
      medical, political, and civic life of Cavendish, Woburn, and the Commonwealth of
      Massachusetts.

PMID- 11512427
TI  - Epilepsia Verminosa.
AB  - Epilepsy is a major public health threat in the developing world, with much
      higher prevalence and incidence rates than those observed in developed countries.
      At present, one of the most common causes for epilepsy worldwide is the parasitic
      worm, Taenia solium, and the associated neurocysticercosis (NCC) that may often
      result from this infestation. Worm infestation was already recognized as a cause
      of epilepsy by the middle of the 18th century. Helminths and their effects on
      health were a daily medical concern in the 18th and 19th centuries--with
      prevailing views ranging from the beneficial effects of the presence of adult
      worms in the gut, to considering them as culprits for a wide variety of diseases.
      A number of cases followed longitudinally by various nineteenth-century French
      physicians showed that there was good reason to believe that the verminous
      influence on seizures was real, as the expulsion of the T. solium often coincided
      with a notable amelioration of symptoms. Several theories were proposed to
      account for how the worms could lead to Epilepsia nervosa, including notions of
      competition for nutritional resources between the host and the parasite, and
      irritation of the medulla and of peripheral nerve endings predisposing to
      epileptiform episodes. Recently, after almost a century of quiet, interest in the
      neurological effects of helminths has been rekindled, due in part to the growing
      number of cases in the United States with NCC-related neurological disorders. In
      this article, we review the history of our understanding of the relationship
      between seizure disorders and parasitic worms, and we relate this history to
      contemporary epidemiologic and public health issues in developing countries.

PMID- 11512428
TI  - Descartes' embodied psychology: Descartes' or Damasio's error?
AB  - Damasio (1994) claims that Descartes imagined thinking as an activity separate
      from the body, and that the effort to understand the mind in general biological
      terms was retarded as a consequence of Descartes' dualism. These claims do not
      hold; they are "Damasio's error". Descartes never considered what we today call
      thinking or cognition without taking the body into account. His new dualism
      required an embodied understanding of cognition. The article gives an historical
      overview of the development of Descartes' radically new psychology from his
      account of algebraic reasoning in the early Regulae (1628) to his "neurobiology
      of rationality" in the late Passions of the soul (1649). The author argues that
      Descartes' dualism opens the way for mechanistic and mathematical explanations of
      all kinds of physiological and psychological phenomena, including the kind of
      phenomena Damasio discusses in Descartes' error. The models of understanding
      Damasio puts forward can be seen as advanced version of models which Descartes
      introduced in the 1640s. A far better title for his book would have been
      Descartes' vision.

PMID- 11512429
TI  - Descartes' error revisited.

PMID- 11512430
TI  - Sources of Damasio's error--a reply to Damasio.

PMID- 11512431
TI  - NEUROwords 11. Arachnophobia: spiders and spider's webs in the head.

PMID- 11512432
TI  - Neurognostics: Question 13: Early anatomical explanation of contralateral
      neurological symptoms.

PMID- 11512433
TI  - Characteristics and lasting contributions of 19th-century American neurologists.
AB  - This project sought to identify characteristics and lasting contributions of 19th
      century members of the American Neurological Association (ANA). Members were
      categorized by elite status, citation frequency, founder or charter member,
      elected to honorary membership, published a monograph on a neurologic or
      psychiatric topic, born in the United States or Canada, and received any medical
      training outside the United States or Canada. Citations to 19th-century
      publications in Science Citation Index were analyzed for the period 1974-1995.
      ANA membership was restrictive, but membership nevertheless increased
      dramatically in the first 25 years from its founding in 1875. 19th-century ANA
      members frequently served in a leadership capacity within the organization,
      published neurologic or psychiatric monographs, and received medical training
      abroad. Highly cited members were more likely to be instrumental in founding and
      developing the organization, and were likely to be recognized by their
      contemporaries as eminent. 19th-century ANA members made significant and lasting
      contributions in many areas of neurology and psychiatry. Articles with lasting
      relevance were early descriptions, points of comparison, and controversial
      articles.

PMID- 11512434
TI  - [Change in the pH of aqueous humor after administration of anti-glaucoma agents
      in rabbits in vivo].
AB  - In this contribution the activity of antiglaucomatics--2% pilocarpine (pH 5.98),
      0.5% timoptol (pH 6.58) and 0.005% xalatan (pH 6.83) is emphasized from the view
      of pH values and changes of the pH values of the rabbit aqueous humor in vitro
      after their application. The rabbit's aqueous humor pH is 7.59--similar to the
      human healthy eye (7.5-7.6). We observed that these antiglaucomatics decrease the
      aqueous humor pH to the acid levels in the following order: 2% pilocarpine > 0.5%
      timoptol > 0.005% xalatan. The most significant decrease was measured immediately
      after the application. From the view of speed of response and effectivity in time
      achieving the pH of the normal aqueous humor we constate the following order:
      0.005% xalatan > 0.5% timoptol > 2% pilocarpine. The changes in pH of the aqueous
      humor after application of these antiglaucomatics are directly connect with their
      physiologic function in the eye. Moreover, they also point out the importance of
      the pH dependence of the antiglaucomatics applicated into the conjunctival sac in
      the treatment of the glaucoma disease.

PMID- 11512435
TI  - [Primary polypseudophakia in patients with cataracts and hypermetropia].
AB  - The authors present clinical results of 22 cataract surgeries of hypermetropic
      eyes in 18 patients (mean age 74 years, range 58-95 years) with primary piggyback
      implantation of two PMMA IOLs both in capsular bag. The surgeries have been
      performed in The Eye Department of The Municipal Hospital in Ostrava. Intraocular
      lens calculations were performed using the SRK II formula. The follow-up period
      was 5 to 36 month (mean 15 month). The mean stabilised postoperative refraction
      was -0.24 D (range -3.5 D to +3.12 D). The mean best corrected visual acuity,
      that reached 0.23, is limited especially by amblyopia and other eye diseases. We
      noticed four secondary cataracts in two patients. There was found no
      interlenticular opacification. Primary implantation more posterior chamber
      intraocular lenses is a good choice for correction hypermetropia during cataract
      surgery.

PMID- 11512436
TI  - [Comparison of ultrasonographic examinations with surgical findings after surgery
      of idiopathic macular hole].
AB  - PURPOSE: In retrospective study to compare echographic features of posterior
      vitreous face and vitreo-macular region with preoperative findings by pars plana
      vitrectomy of idiopathic macular hole. MATERIAL AND METHOD: The group includes 27
      eyes with idiopathic macular hole. 11 in II. and 16 in III. stage by Gass's
      classification. The spectrum of identifiable echographic features included: 1.
      partial posterior vitreous face separation; 2. presence of a pseudooperculum; 3.
      high spike of posterior vitreous face over the macula and/or optic nerve head and
      4. combination of these findings, eventually some other pathology of vitreous.
      Peroperative clinical findings included: 1. presence of a pseudooperculum; 2.
      facility of elevation and separation of posterior vitreous face. RESULTS: The
      echographic findings showed: 1. 5-times (18.5%) partial posterior vitreous face
      separation; 2. 5-times (18.5%) the presence of a pseudooperculum; 3. 4-times
      (14.8%) the high spike of posterior vitreous face in front of the retinal surface
      spike; 4. 10-times (37.0%) the combination of 1. -3. and/or some other pathology
      of vitreous. 3 eyes (11.2%) were without relevant pathologic echographic
      findings. Preoperatively was 1. the presence of a pseudooperculum confirmed in 9
      eyes (33.3%). 6-times (22.2%) the posterior vitreous face had separated by core
      vitrectomy, no active elevation was needed. In 21 eyes (77.8%) the active
      elevation of posterior vitreous face was performed, 6-times (28.4%) was the
      elevation more difficult. CONCLUSION: Echographic features of posterior vitreous
      face and vitreomacular region correlate with preoperative findings by pars plana
      vitrectomy and determine a strategy of surgical intervention.

PMID- 11512437
TI  - [Ultrasonography of choroidal melanoma].
AB  - The authors discuss the use of standardized echography in the diagnosis of
      melanoma of the choroid. They mention the investigated acoustic criteria in
      images B and A (shape, size, limits, site, structure, reflectivity, weakening of
      the ultrasonic signal, vascularization, mobility, consistence) and their
      importance for more detailed identification of the tumour. Investigation of the
      acoustic properties of choroid melanoma and assessment of acoustic criteria for
      echographic assessment of choroid was based on echographic examination of a total
      of 109 bulbi where melanoma was confirmed also by histological examination.

PMID- 11512438
TI  - [Personal experience in the treatment of proliferative diabetic retinopathy using
      an argon laser].
AB  - The authors evaluate the results of treatment of proliferative diabetic
      retinopathy by panretinal photocoagulation with an argon laser in a group of 122
      eyes, 89 patients, with a mean follow-up period of 4.7 years. They achieved
      complete regression of revascularization of 69% eyes, partial regression in 21%
      eyes. In 10% eyes they treatment failed. The resulting visual acuity was 6/12 and
      better in 41% eyes, a visual acuity worse than 6/60 was recorded in 11% eyes. It
      remained unaltered in 70% eyes, deteriorated in 19%. The authors evaluated the
      success rate of laser photocoagulation in relation to the stage and site of
      neovascularizations. They found that the poorest reaction to panretinal
      photocoagulation is obtained in advanced neovascularization of the disc and they
      remain of the known view that advanced neovascularizations display a certain
      grade of autonomy which is the cause of a poorer response to panretinal
      photcogaulation. They confirm former observations that if signs of regression of
      neovascularization develop early, within 3-6 weeks after the onset of laser
      photocoagulation this may be considered a prognostically favourable sign.

PMID- 11512439
TI  - [Additive effects of topical carbonic anhydrase inhibitors].
AB  - The author investigated 23 patients with primary open angle glaucoma treated with
      pilocarpine, timolol, betoptic and latanoprost. Because of inadequate
      compensation of the basic disease dorsolamide was added and the patients were
      followed up for a 12-month period. All combinations decreased significantly the
      intraocular pressure during the long-term follow up. The greatest decrease was
      recorded after a combination of a prostaglandin analogue and dorsolamide.

PMID- 11512440
TI  - [Drainage implants in the treatment of glaucoma. Part III].

PMID- 11512441
TI  - [Etiology and pathogenesis of retinopathy of prematurity (ROP)].

PMID- 11512442
TI  - [A schematic classification of retinopathy of prematurity].

PMID- 11512443
TI  - [Characteristics of diabetic retinopathy in children--part 1].

PMID- 11512444
TI  - [Treatment of diabetic retinopahty in children--part 2].

PMID- 11512445
TI  - [Blindness due to variola in the young Wolfgang Amadeus Mozart].

PMID- 11512446
TI  - A new species of Fusarium producer of galactose oxidase.
AB  - Fifty-two isolates of Fusarium species and one of Gibberella fujikuroi were
      tested for galactose oxidase (GO) production. Five Fusarium isolates contained GO
      activity in the culture filtrate: three F. graminearum and one each F.
      moniliforme f. sp. subglutinans and F. acuminatum. This is the first time F.
      acuminatum is reported to be a producer of GO enzyme. GO enzyme activity produced
      by isolates was assayed through a time course. Moreover, GO protein was partially
      purified from the most productive four isolates to show that the activity
      measured in the culture filtrates was due to the presence of GO protein.

PMID- 11512447
TI  - Factors affecting D-galactonate degradation by extracts of Aspergillus niger.
AB  - Biochemical studies on the degradation of D-galactonate by cell-free extracts of
      Aspergillus niger indicated that the pH value and temperature optima were 8.0 and
      7.5 and 40 degrees C and 50 degrees C for the two enzymes responsible for this
      degradation namely D-galactonate dehydratase and 2-keto-3-deoxy-D-galactonate
      (KDGal) aldolase respectively. The effects of the nature of the buffer substance,
      buffer molarity and enzyme concentration were also studied. Thermal stability
      behaviour studies show that D-galactonate dehydratase was stable at 40 degrees C
      for 60 minutes and about 41%, 80% and 90% of enzyme activity were lost by
      exposing the extracts to 50 degrees C, 60 degrees C and 70 degrees C,
      respectively, for the same period. However, exposing the extracts to 70 degrees C
      after 60 minutes caused a complete inhibition for KDGal aldolase activity and a
      gradual decrease in activity was noticed by incubation the extracts at 60 degrees
      C. The results of freezing and thawing treatment indicated that KDGal aldolase
      was more stable than D-galactonate dehydratase in this respect, as only 27% of
      enzyme activity was lost after 5 days of storage at -5 degrees C. Dialyzing the
      extracts significantly affects KDGal formation from D-galactonate. Results
      obtained also indicated the non-requirement of metal ions for activation of KDGal
      aldolase. On the other, hand D-galactonate dehydratase has a requirement for Mg++
      and Mn++, however ZnSO4 and HgCl2 caused a complete inhibition of the enzymatic
      activity of this enzyme.

PMID- 11512448
TI  - Isolation and characterization of Achromobacter xylosoxidans T7 capable of
      degrading toluidine isomers.
AB  - A bacterial strain capable of utilizing toluidine isomers as its sole source of
      carbon and energy for growth was isolated from contaminated soil. The isolate was
      identified as Achromobacter xylosoxidans and was designated strain T7. Strain T7
      differs from other toluidine-degrading strains with respect to the use of all
      three toluidine isomers even as an equimolar mixture. Additionally, strain T7
      harbours the ability to use aniline, phenol, and cresols as growth substrates.
      Utilization of the toluidine isomers was demonstrated by an increase in the
      bacterial biomass concomitant with a decrease of the respective toluidine
      concentration in liquid medium with this compound as sole source of carbon and
      energy. No accumulation of any intermediate was detectable by HPLC-analyses.
      Results of oxygen uptake experiments with resting cells of strain T7 pre-grown on
      the respective toluidine and enzymatic investigations in cell-free extracts
      indicate the metabolization of the toluidines via the respective methylcatechols
      as intermediates. These compounds are substrates for the meta-cleavage pathway
      initiated by inducible catechol 2,3-dioxygenase found in toluidine-grown cells of
      strain T7.

PMID- 11512449
TI  - Degradation of phenol by Trichosporon sp. LE3 cells immobilized in alginate.
AB  - The degradation of phenol by freely suspended cells of Trichosporon sp. LE3 and
      alginate-immobilized cells was studied in batch culture. The alginate
      concentration (2 or 4%) and the cross-linking salt used (BaCl2 or CaCl2) affected
      the rate and percentage of phenol degradation. The highest values were obtained
      for immobilized cells at 2% calcium alginate, although complete degradation of 15
      and 18 mM phenol was not observed. When the cell concentrations in the assays
      were doubled, the 2% calcium alginate-immobilized cells were able to degrade up
      to 30 mM phenol in less than 120 hours, although the free cells did not
      completely degrade phenol at concentrations above 20 mM. The maximum phenol
      degradation rate was a strong function of initial phenol concentrations, being
      the highest values being observed for 20 mM phenol.

PMID- 11512450
TI  - (-)-Terpestacin and L-tenuazonic acid, inducers of pigment and aerial mycelium
      formation by Fusarium culmorum JP 15.
AB  - Surface cultures of Fusarium culmorum JP15 were found to respond to extracts of
      other fungi by enhanced production of orange-red fusarubin pigments and formation
      of aerial mycelium. Two inducers from strain Ulocladium sp. HKI 0226, the new (-)
      terpestacin (1) and L-tenuazonic acid (2), were isolated. 1 inhibited syncytium
      formation by cells infected with respiratory syncytial virus (RSV).

PMID- 11512451
TI  - Fungal laccase: properties and activity on lignin.
AB  - The sources of ligninocellulose that occur in various forms in nature are so vast
      that they can only be compared to those of water. The results of several, more
      recent experiments showed that laccase probably possesses the big ability for
      "lignin-barrier" breakdown of ligninocellulose. The degradation of this compound
      is currently understood as an enzymatic process mediated by small molecules,
      therefore, this review will focus on the role of these mediators and radicals
      working in concert with enzymes. The fungi having a versatile machinery of
      enzymes are able to attack directly the "lignin-barrier" or can use a multienzyme
      system including "feed-back" type enzymes allowing for simultaneous
      transformation of lignin and carbohydrate compounds.

PMID- 11512452
TI  - [Angiogenesis in bladder: prognosis indicator and therapeutic target].
AB  - Angiogenesis is a complex, multi-step process which leads to the formation of new
      blood capillaries (neovessels) from preexisting vessels. It is essential top the
      growth of solid tumours and tumour metastasis (tumour angiogenesis). This process
      is initiated by the synthesis, by tumour cells and non-malignant tumour
      associated cells, of growth factors called antigenic factors or inducers. bFGF
      (basic Fibroblast Growth Factor) and VEGF (Vascular Endothelial Growth Factor)
      are the two angiogenic factors involved in bladder tumour angiogenesis. The
      angiogenic activity of a bladder tumour can be measured by the microvascular
      density (MVD), considered by some authors to be an independent prognostic
      indicator of recurrence and survival in the group of invasive bladder tumours.
      VEGF expression in bladder tumours and biological fluids (serum, urine) appears
      to be a predictive marker of the risk of progression of superficial bladder
      tumours. Urinary bFGF assay reveals high levels in patients with bladder tumour,
      but this elevation is not specific to bladder tumours. Inhibition of tumour
      angiogenesis has become a therapeutic target. Intravesical suramine and a
      fumagillin analogue (TNP-470) have given promising results in terms of efficacy
      and safety in the treatment of bladder tumours.

PMID- 11512453
TI  - [PC SPES in prostatic cancer: critical review of the literature].
AB  - PC SPES is a mixture of Chinese plants or plant extracts available on
      unrestricted sale since 1996 in the treatment of prostate cancer. Each of its
      components has been individually demonstrated to have an antitumour action anti
      neoplastic in various in vitro or in vivo models. Its favourable action on
      hormone-resistant prostate cancer, demonstrated in studies with only a short
      follow-up, led to a certain publicity concerning this product, and its
      unrestricted sale together with the possibility of purchasing this product in
      other countries by Internet have led to the use of this product by some patients
      in France without medical advice or follow-up. This article presents a critical
      review of the results of this product in prostate cancer.

PMID- 11512454
TI  - [Hand-assisted laparoscopic bi-nephrectomy for refractory arterial hypertension
      in kidney transplantation].
AB  - OBJECTIVE: The authors report their preliminary experience of a manually assisted
      laparoscopic bilateral nephrectomy technique for refractory hypertension in renal
      transplant recipients. MATERIAL AND METHODS: Between April and May 1999, 2
      laparoscopic bilateral nephrectomies were performed with manual assistance using
      the Hand-Port. One patient was operated 4 months before renal transplantation and
      the other was operated 13 months after renal transplantation. Both patients
      presented severe hypertension refractory to several antihypertensive drugs. An 8
      cm midline supra-umbilical incision and 3 trocars were necessary. One hand was
      introduced into the abdominal cavity via the Hand-Port at the beginning of the
      operation. The intra-abdominal hand assisted all phases of dissection of the
      kidney and control of vessels. The renal vessels and ureter were clipped. The
      kidneys were removed by the intra-abdominal hand through the supra-umbilical
      incision. RESULTS: Operating times were 200 min and 130 min. Blood loss was 220
      ml. No conversion was performed. The duration of major postoperative analgesics
      was 3 days. Length of hospital stay was 6 days and 7 days. There were no
      complications. Blood pressure was controlled by bilateral nephrectomy in both
      cases, with significant reduction of antihypertensive therapy. One year after the
      operation, both patients were satisfied with the aesthetic result. CONCLUSIONS:
      Laparoscopic bilateral nephrectomy manually assisted by the Hand-Port is an
      alternative to open bilateral nephrectomy. Larger series are necessary to
      evaluate the morbidity of this technique.

PMID- 11512455
TI  - [Retroperitoneal laparoscopic adrenalectomy: a safe and reproducible technique].
AB  - INTRODUCTION: Laparoscopic adrenalectomy has become one of the reference
      techniques for resection of small tumours of the adrenal gland. The objective of
      this study was to evaluate the retroperitoneal approach in terms of its
      intraoperative complication rate, morbidity and length of hospital stay,
      comparing two centres using the same surgical technique. MATERIAL AND METHOD:
      Between January 1995 and March 2000, two different centres respectively performed
      55 and 60 laparoscopic adrenalectomies (70 left, 45 right) using a
      retroperitoneal incision in 106 patients (64 women and 42 men) with a mean age of
      49.3 years (range: 17 to 74 years). The mean size of the adrenal tumour was 31 mm
      (range: 10 to 61 mm). Five trocars were used in every case. RESULTS: No
      difference was observed between the two centres in terms of operating time (100
      min vs 135 min), conversion rate (0% vs 1.7%), and blood loss (74 ml vs 80 ml).
      With a mean follow-up of 23.4 months, no difference was observed for morbidity
      rate (12.7% vs 16.7%), including intraoperative complications (1.8% vs 5%) with 3
      vascular injuries, and postoperative complications (10.9% vs 11.7%) comprising
      wound abscesses, deep haematomas, a hernia at the trocar orifice and one case of
      severe pneumonia. The mean hospital stay was 3 days vs 5 days with a mean
      duration of analgesic consumption of 2 days (range: 1 to 5 days). CONCLUSION:
      Laparoscopic retroperitoneal adrenalectomy appears to be a reliable and
      reproducible approach for resection of adrenal gland tumours less than 6 cm in
      diameter.

PMID- 11512456
TI  - [Therapeutic aspects of renal abscess. Report of 50 cases].
AB  - INTRODUCTION: Renal abscess often raises therapeutic problems. Based on their
      experience and a review of the literature, the authors propose a treatment plant
      for renal abscess. MATERIAL AND METHODS: The authors report 50 cases of renal
      abscess treated between January 1988 and September 1999 in the Department of
      Urology of Charles Nicolle Hospital in Tunis. The diameter of the abscess was
      less than or equal to 4 cm in 19 cases, between 4 and 10 cm in 29 cases and
      greater than 10 cm in 2 cases. Renal ultrasound and intravenous urography are an
      integral part of the initial morphological assessment. All patients were treated
      by intravenous antibiotics for a mean duration of 28 days. Complementary
      percutaneous drainage of the abscess was indicated in 25 patients. Surgical
      treatment was indicated in 13 patients in the presence of a large perirenal
      collection or severe sepsis, or following failure of percutaneous drainage.
      RESULTS: Antibiotics alone were proposed in only 17 patients with an abscess less
      than 4 cm in diameter and 90% of these patients were cured. Percutaneous
      treatment was performed in 25 patients with an 80% success rate; the other
      patients underwent open surgery. One patient died after surgery in a context of
      septic shock despite salvage nephrectomy. The other patients has a favourable
      outcome. CONCLUSION: The treatment of renal abscess is based on antibiotics alone
      or combined with a percutaneous or surgical drainage procedure depending on the
      size of the abscess and the clinical course. The authors describe their
      decisional flow-chart.

PMID- 11512457
TI  - [Effects of diuretic therapy on spontaneous expulsion of urinary calculi, urinary
      pH, and crystalluria in lithiasic patients].
AB  - OBJECTIVE: High urine volume is known to be an effective measure for preventing
      stone recurrence. However, only few studies have investigated its effects on
      crystalluria and spontaneous passage of calculi. The aim of the study was to
      assess the effects of high diuresis on stone expulsion and recurrence. PATIENTS
      AND METHODS: 219 patients were consulting for a first stone episode in Urology
      units in the Mostaganem area between September 1996 and December 1999. All stones
      were under 6 mm in size. The patients were divided in two groups: group I
      included 129 patients (68 males, 61 females) who agreed to be on a high water
      intake, at least 3 liters per day, over a two months period and to be followed
      periodically by crystalluria examination in the first morning urine; group II
      included 90 patients (63 males, 27 females) who declined diuresis advice and
      urine collection for crystalluria examination. First morning urine collected in
      patients of group I were examined before (2.95 voidings per subject) and while on
      diuresis course (2.84 voidings per subject). For each sample, the urine pH was
      measured and crystals were looked for by polarizing microscopy. Stones
      spontaneously passed were collected and analyzed by infrared spectroscopy. Group
      II represented the control group for stone passing and recurrence. RESULTS:
      Crystalluria was present in 52.4% of urine samples before starting diuresis and
      decreased at 22.9% of urine samples on high diuresis. Mean pH value increased
      from 5.73 +/- 0.46 before to 6.09 +/- 0.47 (p < 10-6) while on diuresis course in
      males and from 5.8 +/- 0.68 to 6.24 +/- 0.66 in females (p < 10-6). The most
      frequent crystalline species was weddellite. Over the study period, 98 patients
      (76%) in group I and only 13 patients (14.4%) in group II passed stones
      spontaneously (p < 10-6 contre group I). No stone recurrence was observed in
      group I while 37.8% of patients in group II presented at least one stone
      recurrence (p < 10-7). CONCLUSION: A high diuresis is an effective measure (1) to
      make easier the passing of stone under 6 mm in size; (2) to reduce the occurrence
      of crystalluria; (3) to reduce significantly, because of its favourable effect on
      urine pH, the formation of pH-dependent crystalline phases, thus decreasing
      heterogeneous nucleation process of calcium oxalate and stone recurrence.

PMID- 11512458
TI  - [Evaluation of tolerance to endovesical BCG treatment in France: analysis of
      severe adverse effects notified in 3 years].
AB  - OBJECTIVES: Intravesical BCG therapy remains the first-line prophylactic
      treatment for recurrences of superficial bladder tumours. However, necessary the
      safety of this medicinal product, for which a potential risk of complications was
      demonstrated during development, needs to be evaluated. MATERIAL AND METHODS:
      Based on spontaneous notifications of adverse events reported according to good
      pharmacovigilance practice and in the context of a survey conducted jointly with
      Health Authorities, the authors present an analysis of adverse event
      notifications received by the manufacturer over a three-year period. A summary of
      serious adverse events (SAE) was established and hypotheses concerning factors
      predisposing to these adverse events were discussed. Finally, practice guidelines
      were formulated. RESULTS: During this period, 97 SAEs were reported
      spontaneously, including 12 local SAEs, 12 regional SAEs and 73 systemic SAEs. 46
      of the 73 systemic SAEs were suspected to be due to BCG infection, 18 were
      related to immune disorders and the cause of 9 SAEs could not be determined.
      Several hypotheses are formulated concerning the circumstances leading to the
      onset of these SAEs and practice guidelines are proposed. CONCLUSION:
      Pharmacovigilance has allowed a better understanding of the qualitative and
      quantitative safety of BCG-IT in France. Hypotheses concerning factors
      predisposing to adverse effects were formulated and practice guidelines were
      proposed. It is essential to continue this collaboration between practitioners,
      Health Authorities and the manufacturer to ensure optimal use of this medicinal
      product.

PMID- 11512459
TI  - [Surveillance and prognosis of "Ta" superficial tumors of the bladder.
      Homogeneous series of 138 cases followed for 1 to 18 years].
AB  - OBJECTIVE: To identify prognostic factors (risk of recurrence and risk of
      progression) and define the rules for the surveillance of stage Ta superficial
      bladder cancers, based on the follow-up of a homogeneous patient series. MATERIAL
      AND METHOD: 138 Ta bladder cancers were recruited from 1975 to 1995 and regularly
      followed by the same urologist. The follow-up was 1 to 18 years with a mean of 66
      months and a median of 60 months. RESULTS: 30% of patients developed no
      recurrence (mean follow-up: 52 months). 70% developed one or several recurrences
      (mean follow-up: 80 months): 46% of Ta recurrences without progression and 24% of
      T > or = 1, with 10% of T > 1 recurrencesed. 13/138 patients died from bladder
      cancer, including 11 patients in less than 10 years. The risk of recurrence and
      the risk of progression were significantly correlated with: the macroscopic
      appearance of the cancer: size, number and extent of implantations, sessile or
      pedunculated nature, its site: slightly more serious on the fixed part of the
      organ, its clinical course assessed over the first 12 months: in patients without
      recurrence at 12 months: the risk of recurrence decreased from 70% to 35% the
      risk of deterioration decreased from 24% to 10%. However, this risk persisted in
      the long term: after more than 5 years without recurrence, 2 patients developed
      fatal recurrences, 11 and 15 years after the initial treatment. CONCLUSION:
      Although superficial, Ta bladder cancers are serious cancers. The risk of
      recurrence and progression justify close surveillance in the year following
      diagnosis. Subsequently, the frequency of follow-up can be adapted to the
      specific course of each case, but, regardless of these modalities, long-term
      (indefinite?) surveillance is recommended.

PMID- 11512460
TI  - [Surveillance and prognosis of "T1" superficial tumors of the bladder.
      Homogeneous series of 88 cases followed for 1 to 22 years].
AB  - OBJECTIVE: Define the prognostic factors (risk of recurrence and risk of
      progression) and the rules for surveillance of stage T1 papillary bladder tumours
      based on the clinical course of a homogeneous patient series. MATERIAL AND
      METHOD: 88 T1 bladder tumours recruited from 1975 to 1995 and regularly followed
      by the same urologist. The follow-up ranged from 1 to 22 years with a mean of 52
      months and a median of 48 months. RESULTS: 26% patients relapsed (mean follow-up:
      71 months) 74% developed one or more recurrences (mean follow-up: 48 months) with
      recurrences staged > T1 in 35% of cases. 29/88 patients died from invasive
      bladder cancer, 14 before 3 years, 19 before 5 years, 28 before 10 years. The
      risk of recurrence and progression was statistically significantly related to the
      macroscopic appearance of the tumour; size, number and extent of implantations;
      its rate of progression assessed by the frequency of recurrence. In patients with
      no recurrence at 12 months, the risk of recurrence decreased from 74% to 50% and
      the risk of progression decreased from 35% to 20%. In this cohort, neither
      histological grading of the initial tumour, nor the degree of invasion of the
      submucosal lamina propria appeared to modify the prognosis. CONCLUSION: Stage T1
      papillary bladder tumours, generally considered to be a superficial tumours
      regardless of their histological grade, have a serious prognosis and warrant
      close endoscopic surveillance during the year following the diagnosis. The
      subsequent frequency of follow-up can then be adapted to the specific mode of
      progression of each case, but, regardless of this mode of progression, the
      authors recommend long-term (life-long?) surveillance.

PMID- 11512461
TI  - [Cancer of the prostate in France: results of the survey CCAFU-FRANCIM].
AB  - OBJECTIVE: The management, diagnosis and treatment of prostate cancer (PC) in the
      general population are poorly defined in France. The objective of this survey was
      to analyse the diagnostic and therapeutic modalities of prostate cancer in 1995,
      on the basis of a population derived from 4 French cancer registries. MATERIAL
      AND METHOD: A sample of 803 PCs diagnosed in 1995 were selected at random from
      the cases listed in the 4 registries (Bas-Rhin, Calvados, Isere and Tarn).
      Analysis by questionnaire concerned the modalities of diagnosis, clinical tumour
      stage and the treatment performed. Clinical stage (TNM 1992) was submitted to
      centralized coding. Logistic regression was used to quantify the various
      practices, taking into account the patient's age, PSA level and clinical stage.
      The probability of receiving each treatment modality was studied by using the
      same clinical determinants. RESULTS: The mean age of the patients was 71.6 years
      (range: 46-94). The clinical stage was T1 or T2 in 60% of cases, T3 or T4 in 14%
      of cases and N+ or M+ in 17% of cases. PSA (median: 18.2 ng/ml) was assayed in
      92.4% of cases. The diagnosis was established by biopsy in 63% of cases and by
      endoscopic resection (TURP) in 32% (5% unknown). The main treatments were:
      radical prostatectomy (RP): 21.9%, radiotherapy: 19.4%, endocrine therapy: 33%,
      isolated TURP: 16.3%, conservative management: 6% and unspecified treatment: 5.6%
      of cases. 31% of cases received combinations of various treatment modalities. RP
      was performed more frequently in patients over the age of 60 years, for T2
      tumours (OR: 3.3) and for 4 < PSA < 20 ng/ml. Radiotherapy tended to be reserved
      for older patients with T3-T4 tumours and 20 < PSA < 50 ng/ml. The frequency of
      endocrine therapy increased with age and PSA (> 50 ng/ml). The frequency of TURP
      and surveillance also increased with age, decreased with high PSA and essentially
      concerned T1 tumours. CONCLUSION: PC was diagnosed relatively early in France in
      1995 with clinically localized tumours in 60% of cases. In this survey, 94% of
      patients received treatment during the year following diagnosis, with 40% of
      curative treatments and 31% of combined treatments.

PMID- 11512462
TI  - [Testicular trauma: report of 56 cases].
AB  - OBJECTIVES: To assess the diagnostic value of clinical examination and ultrasound
      in testicular trauma and to analyse the complications of the various treatments
      proposed (surgical and medical treatments), in order to more clearly define the
      place of medical treatment in this form of trauma in young adults. PATIENTS AND
      METHODS: 56 cases of testicular trauma in 50 patients were managed between
      January 1990 and January 2000. In the absence of clinical and ultrasonographic
      criteria of severity (haematocele, very large intratesticular haematoma, rupture
      of the tunica albuginea), medical treatment consisting of rest, anti-inflammatory
      drugs, and testicular support was instituted. Surgical exploration was performed
      when serious lesions of the testis were suspected. Three subgroup were defined:
      the medical treatment subgroup, the early surgical treatment subgroup, and the
      deferred surgical treatment subgroup (more than 3 days after trauma). The
      immediate morbidity and long-term sequelae were analysed in each of these three
      subgroups. RESULTS: The clinical features of pain and scrotal swelling make
      assessment of the lesions difficult. Testicular ultrasound can help the
      clinician, but it has a low sensitivity for the diagnosis of testicular rupture.
      No significant difference was observed between the three subgroups in terms of
      morbidity, orchidectomy, and long-term sequelae rates. CONCLUSION: In the absence
      of signs of severity, medical treatment with regular surveillance remains
      justified. However, in the case of doubtful clinical or ultrasound findings,
      surgical exploration must be performed as soon as possible.

PMID- 11512463
TI  - [Activity of the autonomous nervous system measured based on the variability of
      heart rate in female urinary incontinence].
AB  - OBJECTIVES: To compare the ANS activity, measured by heart rate variability (HRV)
      in various types of female urinary incontinence (UI). MATERIALS AND METHODS: 25
      patients were included in this prospective study: 11 presented stress UI without
      sphincter incompetence, 9 presented mixed UI and 5 presented urge UI. UI without
      idiopathic detrusor instability (IDI) (n = 11) was compared to UI with IDI (N =
      14.). No statistically significant difference was observed for mean age of the
      patients in the two groups. A 24-hour Holter ECG, under the conditions of the
      patient's everyday life, provided time and frequency indices (Fourier transform)
      of HRV, reflecting the sympathetic, parasympathetic and global ANS activity.
      RESULTS: The global ANS activity of the patients with either mixed UI, urge UI or
      UI with IDI, was statistically significantly lower (p < 0.05) than that of
      patients with stress UI. The sympathetic-vagal balance, heart rate, blood
      pressure, and Ditrovie score were not significantly different between the groups.
      CONCLUSIONS: This preliminary study shows that IDI is associated with a global
      reduction of ANS activity compared to that of patients without IDI. Modifications
      of sympathetic, parasympathetic and global ANS activity were also observed
      between the various types of female UI.

PMID- 11512464
TI  - [Lumbar pain and hydrocalyx].
AB  - The authors report the case of a patient presenting with disabling left lumbar
      pain. Complementary investigations confirmed the diagnosis of isolated hydrocalyx
      with no organic cause. Surgical treatment was conservative with caliceal plasty.
      The authors discuss the diagnostic and therapeutic management by analogy between
      this type of hydrocalyx and Fraley's syndrome.

PMID- 11512465
TI  - [Leiomyosarcoma of the renal vein].
AB  - The authors report a new case of leiomyosarcoma of the right renal vein, marked
      by a rapidly fatal course within 9 months, despite the initial absence of
      metastasis. This exceptional vascular tumour (only about thirty cases have been
      published) must be distinguished from primary renal leiomyosarcoma and
      retroperitoneal leiomyosarcomas involving adjacent structures. This difficult
      diagnosis was suggested by preoperative CT and angiography. Leiomyosarcomas of
      the renal vein generally have an unfavourable outcome in the medium term. The
      prognosis is related to the localized nature of the tumour and the risk of local
      and distant recurrence. Limited tumour resection is rarely sufficient and radical
      nephrectomy is usually necessary, possibly associated with a vascular procedure
      on the inferior vena cava in the case of contiguous extension.

PMID- 11512466
TI  - [Multilocular cystic nephroma in adults. Unusual presentation and review of the
      literature].
AB  - The authors report a case of a multilocular cystic nephroma in an unusual site,
      extensively invading the pelvis and causing atypical symptoms of acute lumbar
      pain. The authors discuss the confusing terminology, the unusual presentation of
      this cystic tumour and the difficulty of establishing a definitive diagnosis of
      its benign nature before the operation in the light of a brief review of the
      literature.

PMID- 11512467
TI  - [Non-functional retroperitoneal paraganglioma].
AB  - Non functional retroperitoneal paragangliomas are rare tumors: less than 50 cases
      are reported in the literature. They are usually asymptomatic and can attain big
      dimensions. The authors report a case diagnosed by histological examination of
      the operative specimen. Malignant tumors more frequent than the benign tumors
      present with a regional extension and delayed metastases. The treatment is
      completed by surgical excision. Radiotherapy and chemotherapy can be used for
      palliation of symptoms.

PMID- 11512468
TI  - [Spontaneous hematoma of the adrenal glands].
AB  - We report an uncommon case of unilateral spontaneous hematoma of the right
      adrenal gland in a 22-year old young man. Preoperative diagnosis was made by
      ultrasonography and CT-scan. A right adrenalectomy was performed. Pathological
      evaluation showed an isolated hematoma without adrenal abnormalities. The
      diagnostic and therapeutic aspects are discussed.

PMID- 11512469
TI  - [Renal lymphangioma].
AB  - The authors report the case of a 39-year-old man presenting with renal colic
      attributed to a renal tumour diagnosed on CT scan. Treatment consisted of total
      nephrectomy in the absence of a definitive intraoperative histological diagnosis
      of renal lymphangioma. Renal lymphangioma is a rare benign tumour, probably
      derived from a congenital malformation of the lymphatic system. Medical imaging
      has certain limits for the diagnosis which can be confirmed by renal needle
      biopsy. Treatment must always be as conservative as possible. The clinical course
      is always favourable.

PMID- 11512470
TI  - [Subcapsular spontaneous hematoma of the kidney of non-tumor origin (report of 5
      cases)].
AB  - Spontaneous subcapsular haematoma (SCH) of the kidney is a rare condition,
      secondary to kidney tumours in more than 50% of cases. Nephrectomy is justified
      in the presence of tumour or uncontrolled haemorrhage. When the aetiology cannot
      be determined, thin-slice CT follow-up of the patient's kidney can be performed.
      The authors report 5 cases of SCH of the kidney. A retropelvic aneurysm was
      responsible for the haematoma in one case; polyarteritis nodosa was the cause of
      bleeding in another case and the aetiology could not be determined in two cases.
      All patients were managed surgically. Nephrectomy was performed in 3 cases and
      simple evacuation of the haematoma was performed in 2 cases.

PMID- 11512471
TI  - [Report of 2 cases of arterio-ureteral fistula].
AB  - Uretero-arterial fistulas are exceptional complications: only about forty cases
      have been reported in the literature. The authors report new two cases of fistula
      between the common iliac artery and the ureter. One fistula occurred in a context
      of prolonged ureteric stenting after radiotherapy and pelvic surgery for cancer
      of the uterus, and the other occurred after an aorto-bifemoral allograft. These
      fistulas generally occur in a particular clinical context, associating several
      aetiological factors. The clinical presentation is dominated by often massive and
      intermittent haematuria. The most useful diagnostic examinations are retrograde
      ureteropyelography and arteriography. The proposed treatment options
      (nephrectomy, vascular bypass graft and even embolization) depend on the urgency
      of the situation and involve both the blood vessel and the urinary tract. The
      prognosis depends on early diagnosis, but preventive measures can be envisaged to
      decrease the risk of appearance of these fistulas in high-risk patients.

PMID- 11512472
TI  - [Uretero-iliac artery fistula: endovascular treatment. Complications of prolonged
      use of double J endoprosthesis].
AB  - The authors report a case of fistula between the external iliac artery and the
      left ureter, in a patient with a double J stent for several years to treat
      iatrogenic ureteric stenosis. The diagnosis was suggested by the patient's
      history and the presence of bright haematuria from the left ureteric meatus.
      Interventional radiology established the positive diagnosis and allowed treatment
      by placement of a covered prosthesis in the external iliac artery. This is the
      fourth published case of endovascular treatment of an iliac uretero-arterial
      fistula.

PMID- 11512473
TI  - [Intraductal adenocarcinoma of the prostate].
AB  - Three patients with a mean age of 69 years presented with endometrioid carcinoma
      of the prostate between 1995 and 2000. With a mean follow-up of 17 months, 2
      patients are alive without metastases and 1 has died from another cause.
      Endometrioid carcinoma represents less than 5% of all prostate cancers. Its
      histological origin has been the subject of controversy for a long time. The
      clinical presentation is often unusual and the natural history is considered to
      be more aggressive than that of the glandular form of prostatic cancer.
      Endometrioid carcinoma of the prostate is not derived from Mullerian structures,
      but from prostatic tissue. It is an unusual form of prostatic cancer, whose
      clinical course and treatment are the same as those of adenocarcinoma.

PMID- 11512474
TI  - [Acute epididymitis disclosing tertiary tuberculosis].
AB  - The authors report the case of a 50-year-old drinker and smoker presenting with
      isolated acute on chronic epididymitis, leading to the diagnosis of tertiary
      tuberculosis. This now exceptional case emphasizes the value of scrotal
      ultrasound and complementary investigations looking for other sites of
      tuberculosis.

PMID- 11512475
TI  - [Endoscopic treatment of vesicorenal reflux in children: short- and long-term
      results of polytetrafluoroethylene (Teflon) injections].
AB  - OBJECTIVE: To retrospectively evaluate the short-term and long-term efficacy and
      safety of endoscopic treatment of vesicorenal reflux in children by
      polytetrafluoroethylene injection, based on the largest series published in the
      literature. MATERIAL AND METHODS: Six hundred and fifty ureters in 402 children
      were by subureteric injection of polytetrafluoroethylene from 1986 to 1993. The
      short-term results were evaluated one month and one year after treatment by
      physical examination, urine culture, bladder and renal ultrasonography and
      retrograde cystography. The long-term results were evaluated with a mean follow
      up of 116 months by physical examination, renal ultrasonography, questionnaire
      for the patient's family and urine culture. RESULTS: 86.6% refluxing ureters in
      82.1% of children were cured after endoscopic treatment. No serious short-term
      complications were observed. In the long-term, 97% of children never presented an
      episode of pyelonephritis. Ultrasonographic assessment did not reveal any
      dilatation of the upper urinary tract, no any suspicious lesions of the bladder
      wall. Continuing reflux nephropathy due to chronic pyelonephritis was observed in
      4.4% of treated kidneys, despite satisfactory correction of reflux. No local
      complications related to the biomaterial and no signs suggestive of distant
      diseases induce by migration of Teflon particles were observed. No malignant
      degeneration was reported. CONCLUSIONS: Review of this series demonstrates the
      short-term efficacy and long-term maintenance of the good results of endoscopic
      treatment of reflux. No local complication and no complications due to migration
      of Teflon were observed in this series. This procedure avoided the need for
      conventional ureteric reimplantation in 92% of treated children.

PMID- 11512476
TI  - [IVU: a test of the past without future?].
AB  - IVU has been gradually replaced over recent years as the "gold standard"
      investigation for the renal parenchyma and urinary tract by two new modalities:
      ultrasound and computed tomography. Some authors still advocate IVU for the
      assessment of renal colic, for the following reasons: the excess cost of CT
      (which is not true for plain CT) and the absence of functional data (there are
      specific CT signs for increased pressure). However, the advantages of CT are
      clearly established: contrast resolution allowing the detection of almost all
      stones except for certain complications of triple combination therapy in HIV
      seropositive patients, extensive cover facilitating identification of
      differential diagnoses, rapidity and greater efficacy, and finally the absence of
      risk related to the injection of iodinated contrast agents in this indication.
      However, the performance of CT may be more limited in certain situations: thin
      patients, or when the female genital tract also needs to be investigated, but IVU
      is not more contributive in this context. The current place of IVU in renal colic
      is therefore to establish a definitive diagnosis and to guide an urgent procedure
      (removal of an obstruction in a context of infection) when CT is either
      unavailable (maintenance...) or really excessively irradiating, as in pregnant
      women, when ultrasound, or even MRI and MR urography have not been sufficiently
      contributive. The essential indication remains detailed visualization of the
      urinary tract (assessment of haematuria, detection of an urothelial tumour),
      detailed visualization of the entire urinary tract (assessment of certain
      malformations), or even a gross assessment of renal function in a patient with
      multiple injuries, which cannot be investigated by CT and in whom the surgeon
      rightly hesitates before opening the retroperitoneum. However, in the absence of
      IVU, we may fail to diagnose papillary necrosis or a small caliceal diverticulum,
      but is that really important in the final analysis? IVU, in countries with
      adapted equipment, is therefore now only an expert examination. IVU is an
      examination of the past, without a future indeed, but with a descendant: CT
      urography.

PMID- 11512477
TI  - [Pierre-Francois-Olive Rayer (1793-1867): one of the founders of modern uro
      nephrology].
AB  - Rayer's scientific work is extended on several fields of the medicine. His most
      considerable contribution concerns dermatology, anatomopathology, infectious
      pathology and medical chemistry. However, thanks more particularly to his work on
      uro-nephrology, Rayer is considered as one of the founders of this discipline.

PMID- 11512478
TI  - Gold Medal Award for Life Achievement in the Application of Psychology.

PMID- 11512479
TI  - Gold Medal Award for Life Achievement in Psychology in the Public Interest.

PMID- 11512481
TI  - Gold Medal Award for Life Achievement in the Practice of Psychology.

PMID- 11512480
TI  - Gold Medal Award for Life Achievement in the Science of Psychology.

PMID- 11512482
TI  - Award for Distinguished Teaching in Psychology.

PMID- 11512483
TI  - 2000 report of the Policy and Planning Board.

PMID- 11512484
TI  - Composition of the Council of Representatives. Report on the apportionment ballot
      for representation year 2002.

PMID- 11512485
TI  - Report of the Ethics Committee, 2000.

PMID- 11512486
TI  - Evaluation of school-based HIV prevention education programs in New Jersey.
AB  - This paper presents results from a process evaluation conducted by the New Jersey
      Department of Education (NJDOE). Representative samples of middle and high school
      superintendents, principals, lead health teachers, and HIV teachers provided
      information assessing whether local district policy content was consistent with
      the state's policy code, the dynamics of local policy development, and school
      district staff perceptions and practices regarding HIV education policies. NJDOE
      also was interested in determining: if inservice training was accessible to
      teachers assigned to provide HIV education; the scope and impact of HIV inservice
      programs; and the training needs of staff assigned to teach the HIV curriculum.
      Finally, NJDOE was interested in determining: local curricula scope, sequence,
      and approach; the extent to which local curricula were skills-based; and local
      expectations for instructional outcomes. As a result of the evaluation, program
      staff identified areas needing remediation and planned for program improvement in
      new areas.

PMID- 11512487
TI  - Multidisciplinary teaming to promote effective management of type 1 diabetes for
      adolescents.
AB  - Intensive diabetes therapy can reduce the long-term microvascular complications
      of Type 1 diabetes and improve glucose control. Managing the demands of intensive
      therapy however, often poses a burden on adolescents and their families. Through
      multidisciplinary teaming, the school health office can facilitate active
      participation in treatment, coordinate services, and maximize use of community
      resources. This paper presents a general overview of intensive diabetes therapy,
      psychosocial implications of chronic illness in adolescence, effects of chronic
      illness on the family, and behavior change strategies to improve adherence with
      disease management guidelines.

PMID- 11512488
TI  - A study of young adults who provide tobacco products to minors.
AB  - Teens acquire tobacco from social sources. This study examined factors related to
      young adults providing tobacco products to minors. Variables such as
      demographics, rate and method of provision, attitudes toward provision, and youth
      access restriction laws were measured. A sample of 250 college students completed
      the survey. About 33.2% of those young adults were asked to provide tobacco to
      minors, and 30.8% of these students provided it. Students in health-related
      majors were as likely to be approached and to provide tobacco as were nonhealth
      majors. Males were more likely to be approached and to provide tobacco to minors
      than were females. Convenience stores and gas stations were the most popular
      locations. Young adults favored laws that restrict minors from purchasing
      tobacco, and their intention to give tobacco in the future was the best predictor
      of providing tobacco to minors.

PMID- 11512489
TI  - The relationship of adolescent perceptions of peer norms and parent involvement
      to cigarette and alcohol use.
AB  - This investigation assessed the relative influence of peer norms and parental
      involvement on adolescent cigarette and alcohol use. An anonymous questionnaire
      was administered to 2,017 seventh- to 12th-grade students in two Ohio public
      school districts. Cigarette and alcohol use rates in the sample were comparable
      to those found in national probability surveys. Results indicated that the
      relative balance of peer-parent influences did not differ across grade level. At
      all grade levels, perceived peer norms had substantially greater correlations
      with cigarette and alcohol use than did measures of perceived parental
      involvement. The findings are interpreted from an efficiency perspective. Optimal
      use of prevention resources suggest that programming for seventh- to 12th-graders
      should focus on shaping the perceptions of peer smoking and drinking practices
      rather than on parent interventions. Social norms marketing or other forms of
      normative education should be tested in this population.

PMID- 11512490
TI  - Principal and teacher reports of strategies to enforce anti-tobacco policies in
      Florida middle and high schools.
AB  - This study describes anti-tobacco policies implemented by middle and high schools
      in Florida. All schools had in place formal anti-tobacco policies but
      implementation of those policies was more rigorous at the middle school level.
      Principals and tobacco use prevention education teachers reported the formal and
      informal strategies used to enforce their school's anti-tobacco policies.
      Punitive enforcement strategies were more commonly reported than nonpunitive
      strategies. Enforcement strategies were significantly associated with several
      features of school settings including number of supports for teachers' efforts,
      teachers' perceptions of program success, and training opportunities for
      teachers. Middle school staff reported using significantly more enforcement
      strategies than high school staff, and their strategies were more likely to be
      associated with school context variables. Implications of these findings for the
      maintenance of anti-tobacco programs in secondary schools are discussed.

PMID- 11512491
TI  - Safe and drug-free school coordinators' perceived needs to improve violence and
      drug prevention programs.
AB  - A random sample of 380 Ohio safe and drug-free school coordinators was mailed
      surveys regarding their perceived needs to improve safe and drug-free school
      programs. Of 298 who responded (78%), most were White (88%), female (71%), older
      than age 40 (72%), possessed a master's degree (56%), and worked at either a
      rural (43%) or suburban (40%) school. Training topics perceived as most
      beneficial in improving safe and drug-free school programs included training on
      effective techniques that enhance youth success, building school-parent-community
      partnerships, and providing conflict management/dispute resolution skills. Lack
      of time, poor parental attitudes, and lack of school personnel support were
      identified most often as barriers to program improvement. Findings can be used by
      state health education resource centers and training providers to more
      effectively meet the needs of safe and drug-free school coordinators.

PMID- 11512492
TI  - Student satisfaction with the student health service at Escuela Preparatoria No.
      5 in Guadalajara, Mexico.

PMID- 11512493
TI  - Role of tryptophanyl residues in driving myoglobin folding.
AB  - Mammalian myoglobins contain two tryptophanyl residues at the invariant positions
      7 (A-5) and 14 (A-12) in the N-terminal region (A helix) of the protein molecule.
      The simultaneous substitution of both tryptophanyl residues causes an incorrect
      folding with subsequent loss of heme binding. The introduction of a indolic
      residue in different molecular regions, i.e. G, E, and C helix resulted in a not
      correctly folded protein, suggesting that the tryptophanyl residues are strong
      structural determinants.

PMID- 11512494
TI  - Rat serum improves rat pseudoislet formation and insulin gene expression.
AB  - Rat islet cells in culture are able to form tridimensional aggregates with an
      architecture and functional activity similar to native islets: pseudoislets.
      Pseudoislets represent an alternative source for islet transplantation, because
      their transplant results in a long term allograft acceptance without
      immunosuppression of the host. Use of pseudoislets has been limited by their
      reduced yield and by poor reaggregation mass. Since culture conditions have been
      reported to affect reaggregation, the aim of this study was to evaluate the
      effects of different concentrations of two sera (Fetal Bovine Serum [FBS] and Rat
      Serum [RS]) on reaggregation and insulin gene expression in pseudoislets. Islets
      were isolated from male Lewis rat by means of histopaque gradient centrifugation.
      The day after islets were disrupted into single cells and cultured in RPMI 1640
      5.6 mM glucose with 2%, 5% and 10% solutions of both FBS and RS. Cells
      spontaneously reaggregated to form pseudoislets. After seven days of culture,
      pseudoislets were counted and analysed for insulin secretion and insulin gene
      expression using RT-PCR. Rat serum increased the number of aggregates and their
      diameters. Insulin gene expression of pseudoislets cultured with RS showed a ten
      fold increase in comparison to those cultured with FBS. These data show that the
      culture medium supplemented with RS improves total reaggregate volume and
      increases insulin gene expression. With the perspective of pseudoislets' use in
      transplantation RS is better indicated than FBS for the production of rat
      pseudoislets.

PMID- 11512495
TI  - Inorganic mercury in the rock pool environment (Ligurian Sea).
AB  - In the present study the mercury concentration has been investigated in three
      components of a rock pool environment of Genoa Nervi (Ligurian Sea): water,
      particulate matter and Tigriopus fulvus (Harpacticoid copepod). The influence of
      some parameters (pH, temperature, salinity, rainfall) on mercury concentration
      has been evaluated. These data show that the mercury concentration is greater in
      Tigriopus males than in females and that the concentration also depends on
      temperature variations.

PMID- 11512496
TI  - Chronic hypertension in pregnancy.
AB  - Pregnant women with chronic hypertension are at risk for maternal and perinatal
      morbidity. Careful assessment and management of these patients during pregnancy
      are the keys to reducing maternal and fetal complications. Antihypertensive
      treatment should be used in women with high-risk chronic hypertension, whereas
      drug therapy does not improve pregnancy outcome in women at low risk.
      Prophylactic low-dose aspirin started early in pregnancy in women with chronic
      hypertension is not effective in reducing the frequency of superimposed
      preeclampsia and should be avoided.

PMID- 11512497
TI  - Cardiac disease and pregnancy.
AB  - The pregnant state imposes a supraphysiologic strain on the pregnant woman's
      cardiac performance through complex biochemical, electric, and physiologic
      changes affecting the blood volume, myocardial contractility, and resistance of
      the vascular bed. In the presence of underlying heart disease, these changes can
      compromise the woman's hemodynamic balance, her life, and that of her unborn
      child. Cardiac pathology represents a heterogeneous group of disorders, each with
      its own hemodynamic, genetic, obstetric, and social implications. Physicians
      caring for these women should actively address the issue of reproduction.
      Ideally, pregnancy should be planned to occur after optimization of cardiac
      performance by medical or surgical means. Once pregnancy is achieved, the
      concerted effort of a multidisciplinary team of obstetricians, cardiologists,
      anesthesiologists, nursing, social, and other services provides the best
      opportunity to carry the pregnancy to a successful outcome.

PMID- 11512498
TI  - Diabetes complicating pregnancy.
AB  - Despite the well-documented relationship between morbidity in pregnancy and
      pregestational maternal diabetes, the corrected perinatal outcome is, in most
      series, equal to or better than that of the general reference obstetric
      population. No single aspect or element of contemporary management is responsible
      for this improvement; rather, a combination of interventions seems responsible.
      Targeting delivery early in term, improved compliance, better glycemic control
      during pregnancy, improved control at conception, improved neonatal care, family
      planning, and early screening for fetal abnormalities all likely contribute to
      improved outcome. The currently observed rates of perinatal mortality suggest
      that an irreducible minimum mortality rate may be reached; however, large
      disparities in access to care and treatment continue to result in a wide range in
      rates of morbidity and mortality, a fact that pertains to outcomes in general as
      well as to pregnancies complicated by diabetes. The identification of women with
      lesser degrees of hyperglycemia as diabetic by lowering the thresholds for
      glucose tolerance test abnormality suggests an importance of the diagnosis that
      is not supported by evidence of either related morbidity or therapeutic benefit.
      The extrapolation of risk to women with lesser degrees of hyperglycemia seems to
      have little basis, and the management of women with mild glucose intolerance as
      if they had overt diabetes is unwarranted. The excess of resources dedicated to
      the identification and monitoring of an increasing number of women with mild
      abnormalities of glucose metabolism should prompt a reevaluation of these
      practices. Perinatal benefits of this expenditure are difficult to document or
      nonexistent, and there is a predictable increase in iatrogenic morbidities
      associated with the diagnosis. The exception in the most recent recommendations
      is the addition of a random glucose measure to screen for the rare women with
      overt undiagnosed diabetes who presents for prenatal care, because these women
      are at increased risk of morbidities related to diabetes. A curious statement was
      made in the summary and recommendations of the fourth International Congress on
      Gestational Diabetes: "There remains a compelling need to develop diagnostic
      criteria for GDM [gestational diabetes mellitus] that are based on the specific
      relationships between hyperglycemia and risk of adverse outcome." If these
      relationships are undefined, what is the import of the diagnosis? At the author's
      center, application of the new diagnostic thresholds for the diagnosis of
      gestational diabetes mellitus has increased the incidence to over 6%. Without a
      clear expectation of benefit, this increase represents an unsupportable
      investment of resources. What are the prospects for improving understanding of
      the relationships between glucose intolerance and pregnancy risks? The direction
      of new guidelines and recommendations seems to be moving away from resolution of
      the relationships. The new criteria result in the diagnosis of gestational
      diabetes in an increasing number of women who were previously normal. It is
      easier to differentiate women at an extreme of hyperglycemia from normal.
      Investigations will be even less able to identify attributable effects of glucose
      intolerance in pregnancy with the inclusion of women with lesser degrees of
      hyperglycemia. As evidenced in O'Sullivan's original series, women with fasting
      hyperglycemia in pregnancy are still presumed to be at increased risk of fetal
      death. This risk factor remains important in clinical management if insulin
      treatment, fetal surveillance, and early term delivery can reduce the risk of
      fetal loss. At the author's center, the relationships among outpatient measures
      of fasting glycemia, glucose tolerance testing results, and perinatal outcomes
      are evaluated. Preliminary results suggest that fasting glycemia measured at the
      time of a 50-g glucose tolerance test is significantly correlated with and as
      sensitive and predictive of morbidity as the glucose tolerance test diagnosis of
      gestational diabetes. If these results are confirmed, it will be difficult to
      rationalize continued glucose tolerance testing.

PMID- 11512499
TI  - Asthma in pregnancy.
AB  - Contemporary management of the pregnant asthmatic is directed at controlling
      symptoms and treating the underlying cause of asthma, namely, inflammation. This
      article discusses the pathophysiology of asthma and the effects of asthma on
      pregnancy and vice versa and reviews the National Asthma Education Program
      guidelines for the treatment of asthma in pregnancy.

PMID- 11512500
TI  - Pneumonia in pregnancy.
AB  - Although the advent of broad-spectrum antibiotics has markedly improved the
      maternal outcomes of pneumonia complicating pregnancy, pneumonia remains a
      significant condition that may complicate pregnancy. This article has reviewed
      the inherent physiologic respiratory changes that accompany pregnancy and the
      common causes of pneumonia in the pregnant woman. The clinical course of
      bacterial pneumonia seems to be minimally altered by pregnancy, whereas viral
      pneumonia carries a significantly worse prognosis when encountered during
      gestation. Prompt diagnosis, the initiation of respiratory support, and
      appropriate antimicrobial/antiviral therapy are key components of therapy for
      women in whom pregnancy is complicated by pneumonia. Because preterm labor
      frequently accompanies pneumonia, women should be monitored closely for the
      occult onset of preterm labor and appropriate interventions initiated if
      indicated. Perhaps even more important than interventions to treat acute
      pneumonia are efforts directed at active immunization or prophylactic therapy to
      prevent the development of pneumonia in select patient populations. The
      combination of these efforts is essential to optimize medical care for pregnant
      women.

PMID- 11512501
TI  - Disease of the gallbladder and pancreas in pregnancy.
AB  - Although maternal mortality and morbidity are substantially lower today than
      decades ago, perinatal mortality and morbidity secondary to gallbladder and
      pancreatic disease remain excessive. Improvements in perinatal mortality reflect
      improvements in neonatal intensive care because most of the morbidity stems from
      prematurity. Prompt recognition of cholelithiasis and pancreatitis and liberal
      hospitalization have been associated with a decline in poor outcomes. The
      decision to switch from medical to surgical management must be made individually,
      taking into account past history, gestational age, and the response of current
      disease to conservative therapy.

PMID- 11512502
TI  - Urinary tract infections during pregnancy.
AB  - Urinary tract infections are relatively common in pregnancy and may result in
      significant morbidity for the pregnant woman and fetus. The authors recommend
      that all pregnant women be screened for the presence of bacteriuria at their
      first prenatal visit. Failure to treat bacteriuria during pregnancy may result in
      as many as 25% of women experiencing acute pyelonephritis. Women with acute
      pyelonephritis may sustain significant complications, such as preterm labor,
      transient renal failure, ARDS, sepsis and shock, and hematologic abnormalities.
      Pregnant women with urinary tract infections should be followed up closely after
      treatment because as many as one third will experience a recurrence.

PMID- 11512503
TI  - Renal disease in pregnancy.
AB  - Women with renal disease who conceive and continue a pregnancy are at significant
      risk for adverse maternal and fetal outcomes. Risk is inversely related to the
      degree of renal insufficiency. Pregnancy-induced changes in the urinary tract can
      temporarily increase renal function compromise, such as nephrosis, but most often
      results in no net increase in dysfunction. Common complications of pregnancy-
      such as hypertension and hypovolemia--can be associated with acute renal injury
      or aggravation of pre-existing disease.

PMID- 11512504
TI  - Seizure disorders in pregnancy.
AB  - Epilepsy is the presence of two or more seizures in the absence of an
      identifiable cause for the seizures; that is, no intracranial or metabolic
      abnormality. Epilepsy affects approximately 1% of the US population, which
      represents an estimated 1.1 million women of reproductive age. The management of
      women with epilepsy during pregnancy is the focus of this article.

PMID- 11512505
TI  - Venous thromboembolism and pregnancy.
AB  - Venous thromboembolism remains a major cause of maternal morbidity and mortality.
      Pregnancy is a thrombogenic state; therefore, clinicians must be familiar with
      the diagnosis and treatment of acute VTE. It is of paramount importance when
      caring for pregnant women to understand which patients are at risk for VTE and to
      use thromboprophylactic heparin accordingly.

PMID- 11512506
TI  - Adjuvant therapy for breast cancer.
AB  - OBJECTIVE: To provide health care providers, patients, and the general public
      with a current consensus on various issues related to the use of adjuvant therapy
      for breast cancer. PARTICIPANTS: A nonfederal, nonadvocate, 14-member panel
      representing the fields of oncology, radiology, surgery, pathology, statistics,
      public health, health policy, and the public; 30 experts in medical oncology,
      molecular oncology, biostatistics, epidemiology, surgical oncology, and clinical
      trials who presented data to the consensus panel; a conference audience of
      approximately 1,000. EVIDENCE: The literature was searched using MEDLINE and an
      extensive bibliography of references was provided to the panel. Experts prepared
      abstracts with relevant citations from the literature. Scientific evidence was
      given precedence over clinical anecdotal experience. CONSENSUS PROCESS: The
      panel, answering predefined questions, developed their conclusions based on the
      scientific evidence presented in open forum and the scientific literature. The
      panel composed a draft statement that was read in its entirety and circulated to
      the experts and the audience for comment. Thereafter, the panel resolved
      conflicting recommendations and released a revised statement at the end of the
      conference. The panel finalized the revisions within a few weeks after the
      conference. The draft statement was made available on the World Wide Web
      immediately following its release at the conference and was updated with the
      panel's final revisions. CONCLUSIONS: During the past 10 years, substantial
      progress has been made in the treatment of invasive breast cancer. For the first
      time, breast cancer mortality rates are decreasing in the United States.
      Refinements of adjuvant treatment have contributed to this advance. Generally
      accepted prognostic and predictive factors include age, tumor size, lymph node
      status, histological tumor type, grade, mitotic rate, and hormonal receptor
      status. Novel technologies, such as tissue and expression microarrays and
      proteomics, hold exciting potential. Progress, however, will depend on proper
      design and analysis of clinical and pathological investigations. Decisions
      regarding adjuvant hormonal therapy should be based on the presence of hormone
      receptor protein in tumor tissues. Adjuvant hormonal therapy should be offered
      only to women whose tumors express hormone receptor protein. Because adjuvant
      polychemotherapy improves survival, it should be recommended to the majority of
      women with localized breast cancer regardless of nodal, menopausal, or hormone
      receptor status. The inclusion of anthracyclines in adjuvant chemotherapy
      regimens produces a small but statistically significant improvement in survival
      over non-anthracycline-containing regimens. Available data are currently
      inconclusive regarding the use of taxanes in adjuvant treatment of node-positive
      breast cancer. The use of adjuvant dose-intensive chemotherapy regimens in high
      risk breast cancer and of taxanes in node-negative breast cancer should be
      restricted to randomized trials. Ongoing studies evaluating these treatment
      strategies should be supported to determine if they have a role in adjuvant
      treatment. Studies to date have included few patients older than 70 years. There
      is a critical need for trials to evaluate the role of adjuvant chemotherapy in
      these women. There is evidence that women with a high risk of locoregional tumor
      recurrence after mastectomy benefit from postoperative radiotherapy. This high
      risk group includes women with four or more positive lymph nodes or an advanced
      primary cancer. Currently, the role of post-mastectomy radiotherapy for patients
      with one to three positive lymph nodes remains uncertain and should be tested in
      a randomized controlled trial. Individual patients differ in the importance they
      place on the risks and benefits of adjuvant treatments. Quality-of-life needs to
      be evaluated in selected randomized clinical trials to examine the impact of the
      major acute and long-term side effects of adjuvant treatments, particularly
      premature menopause, weight gain, mild memory loss, and fatigue. Methods to
      support shared decision-making between patients and their physicians have been
      successful in trials; they need to be tailored for diverse populations and should
      be tested for broader dissemination.

PMID- 11512507
TI  - [Outcome of urinary diversion (quality of life)].

PMID- 11512508
TI  - [Usefulness of the dynamic sentinel node technique in patients with penile
      carcinoma].
AB  - OBJECTIVE: To explain and analyse when and how to use the new staging technique
      used in patients with squamous carcinoma of the penis, through the procedure of
      dynamic biopsy of the sentinel lymph node. PATIENTS AND METHODS: We demonstrate
      the technical application of the dynamic biopsy of the sentinel lymph node, in a
      40-year-old patient, diagnosed as suffering from squamous carcinoma of the penis.
      We use preoperative lymphatic visualization through lymphogammagraphy, together
      with intraoperative detection through gamma scanning, in order to detect and
      identify the sentinel lymph node. CONCLUSIONS: We consider the dynamic biopsy of
      the sentinel node by the individual pattern of the lymphatic drainage as a new
      applicable Nuclear Medicina technique. It is an extremely useful technique in
      order to achieve early dissemination, by allowing us to identify patients with
      sub-clinic lymphatic spread, who will be candidates to regional lymphatic
      dissection.

PMID- 11512509
TI  - [Descriptive study of bladder tumors in the district of Levante-Alto Almanzora].
AB  - We present our series of operater bladder cancers in this District and the annual
      incidence in the period 1996 at 1998, as web as they are distributed by sex, age
      and smoking in the population; neoplasic stage and relapse were also studied. 61
      patients were treated and un found global half incidence of 19.8 for 10(5)
      inhabitant-year (h-a), while for sexes it was of 4.22 for 10(5) h-y for women and
      of 15.58 for 10(5) h-y males. 78.69% was male with a masculinity rate of 3.69.
      The most frequent age group was starting from the seventh decade with 50.81% of
      our series. There was 36% of intervened patients that they were smoking, while
      29.5% had relationship with other factors of risk like hydrocarbons and
      pesticidas. The superficial tumors were the most frequent with 86.88% of the
      cases, on the other hand the undifferentiated neoplastics was not very frequent
      with 13.21%, increasing these neoplastics with the age. In the follow up there
      were relapses in 36% of the people, being bigger in the T1 of our series. The
      occupational factors in this district can explain the high frequency in the
      female sex, although analytic studies are needed to check it.

PMID- 11512511
TI  - [Personal treatment of congenital penile curvature].
AB  - Severe type I congenital curvature of the penis is characterised by an almost
      transparent hypoplasia uretra. Treatment consists of resecetion of the dysplasic
      urethra and its replacement by tubular grafts of preputial or extragenital skin
      or of the vesical or buccal mucous membrane. We present our experience of four
      patient with type I congenital curvature of the penis which we treated with a
      simple surgical technique consisting of leaving the over-lying skin attached to
      the hypoplasia urethra and resecting the remaining fibrotic tissue which is
      connected to and retracts the skin and the cavernous bodies. We performed plastic
      surgery of the dorsal surface of the tunica albuginea to achieve correct penis
      hardening and finalized the surgery with reconstruction of the ventral surface of
      the penis by spreading out the dorsal prepuce or by using a pediculated graft of
      surplus preputial skin.

PMID- 11512510
TI  - [Treatment of female stress urinary incontinence with the TVT (tension-free
      vaginal tape) system: our experience].
AB  - INTRODUCTION: The TVT system is a new surgical procedure for female stress
      urinary incontinence. The object of this study is to report our initial
      experience with this technique. We report our results and complications too.
      MATERIAL AND METHODS: From April 1999 to July 2000, 23 systems TVT was implanted
      in our hospital. The patients were followed for a 6 to 21 month period. All the
      patients had stress incontinence. The mean age was 59 years. Gynaecological
      surgery was associated in 4 patients. One of them was excluded because a
      diagnosis mistake. TVT implies the implantation of a prolene tape around mid
      urethra via a minimal vaginal incision. RESULTS: 17 patients (77.27%) had a
      significantly improved in the post-operative evaluation. The mean post-surgical
      stay in the hospital was 1.7 days. A bladder base was damaged during the surgery.
      No urinary retention, erosion or urethral lesion were found. CONCLUSIONS: We
      consider the TVT operation to be a safe and effective surgical procedure for the
      treatment of female urinary stress incontinence. This surgery is easy to lean,
      fast, cheap and with a low rate of complications.

PMID- 11512512
TI  - [Quality of life in patients treated with orthotopic bladder substitution versus
      cutaneous ileostomy].
AB  - PURPOSE: Nowadays, psychcological and social aspects of treatment of urinary
      diversion after cystectomy, have become of utmost importance. Body image,
      potency, continence, emotional distress and dissatisfaction, functional and
      social activities are majors factors to improve quality of life after surgery.
      The aim of this study is to compare health-related quality of life after bladder
      substitution with ileal conduit diversion. MATERIALS AND METHODS: We developed a
      questionnaire based upon a literature review, to compare health related quality
      of life between bladder substitution and ileal conduit (45 multiple choice mailed
      questionnaire). We examined functional and social activities, sexual dysfunction,
      urinary problems, and body image dissatisfaction. RESULTS: 78 male patients with
      bladder cancer, were interviewed. 91% of the questionnaires were answered, 48.7%
      by patients' family and 42.3% by the patients themselves. 6 patients underwent
      ileal conduit and 27 underwent bladder substitution. Patients with ileal consuit
      presented higher body image dissatisfaction than those who underwent bladder
      substitution. When urine leakage occurred it caused more distress to the conduit
      patients, indicating urinary leakage as their main problem. Bladder substitution
      patients did not consider continence problems as very important, they had not
      interrupted social activities such as travelling or seeing friends. 100% of
      bladder substitution patients would not mind to undergo this operation again,
      while only 66% of ileal conduit patients would. CONCLUSION: Health-related
      quality of life is higher after bladder substitution. In our opinion we should
      use bladder substitution as the standard method of diversion after radical
      cystectomy for bladder cancer.

PMID- 11512513
TI  - [Prostatic leiomyosarcoma. Report of a case a review of the literature].
AB  - A 48-year-old male with a leiomyosarcoma of the prostate is presented. The
      clinical presenting features were those of rapidly evolving prostatism and rectal
      symptoms (rectal bleeding, sense of rectal fullness and perineal pain). Arising
      from the smooth muscle cells of the prostate gland, this is a rare neoplasm that
      account for less than 0.1% of prostate malignancies, with a poor prognosis. It is
      often difficult to determine a definite origin, being necessary the differential
      diagnosis with pseudosarcoma, inflammatory fibrosarcoma, prostate abscess and
      other rare tumors. There is no established protocol of treatment. Combined
      modality therapy including radical surgery, radiation therapy and chemotherapy
      seems to be the best, although prognosis remains poor.

PMID- 11512514
TI  - [Urinary incontinence caused by urocolpos. Report of a new case].
AB  - We present a new case of urocolpos that appeared as urinary incontinence. We
      discuss the etiology and the available therapeutic choices, emphasizing on the
      value of the clinical history and physical exploration showed data.

PMID- 11512515
TI  - [Urethral nephrogenic adenoma in a young male. Report of a case].
AB  - Nephrogenic adenoma is a rare urothelial neoformation. It is well known the
      association to infective diseases and stones; the most common localization is in
      the bladder. We report the case of a young male without previous disease who
      showed a nephrogenic adenoma in the urethra, it was managed with transurethral
      resection and surveillance.

PMID- 11512516
TI  - [Urethro-vesical foreign bodies].
AB  - We report the case of a squizoid 45 year old man who presented an acute urinary
      retention and had several foreign bodies in the urethra and bladder.

PMID- 11512517
TI  - [Uterine perforation and vesical migration of intrauterine device].
AB  - Cases of uterine perforation through to the bladder during the placement of an
      intrauterine device are rare. There have been only 25 previous reported cases.
      This type of perforation is no different to any other by an intravesical foreign
      body. A detailed anamnesis and sonographic examination is usually sufficient to
      provide a diagnosis. Complications can be diagnosed by an uretrocytoscopy which
      is also therapeutic in non-complicated cases. If there are associated
      complications surgery can be necessary. In conclusion, quick detection of any
      complication, by sonographic detection after placement, assists in the extraction
      of the foreign body and avoids the appearance of associated complications such as
      lithiasis.

PMID- 11512518
TI  - [Analysis of calculi in the era of extracorporeal lithotripsy. (13th National
      Meeting of Urolithiasis and Urinary Endoscopy)].

PMID- 11512519
TI  - Aminoglycoside-modifying enzymes: mechanisms of catalytic processes and
      inhibition.
AB  - The most prevalent mechanism for resistance to aminoglycoside antibiotics is
      mediated through their enzymatic modification in resistant organisms. Dozens of
      aminoglycoside-modifying enzymes are known at the gene sequence level, but few
      have been characterized in the details of their mechanism. This review summarizes
      the state of knowledge of the best studied of these enzymes, focusing on their
      catalytic mechanisms and inhibition.

PMID- 11512520
TI  - Lamivudine resistance in hepatitis B: mechanisms and clinical implications.
AB  - Lamivudine (beta-L-(-)-2',3'-dideoxy-3'-thiacytidine) has been a major
      breakthrough in the care of patients with hepatitis B. With prolonged monotherapy
      the development of resistance is an increasingly recognized problem that limits
      the long term efficacy of this nucleoside analogue. The most common mutations
      associated with lamivudine resistance occur within the highly conserved YMDD
      motif in the C domain of the viral polymerase and are often associated with a
      compensatory mutation in the proximal B domain. The structural and functional
      relationship of resistance mutations is reflected in different in vitro
      sensitivities to lamivudine and changes in replication capacities. During
      prolonged lamivudine treatment there can be successive changes of different
      resistant mutants (genotypic succession) or a single mutant can remain the
      dominant viral species. In patients treated for chronic hepatitis B infection the
      cumulative incidence of viral resistance reaches over 50% after 3 years. Most
      patients will have lower serum HBV DNA levels after the emergence of resistance
      which is ascribed to the decreased replication capacity of these mutants.
      Although severe flares and ongoing HBe antigen seroconversion can occur in these
      patients with lamivudine-resistant HBV, the impact of continued therapy on the
      long-term outcome is still insufficiently studied. In the setting of liver
      transplantation for HBV-associated disease the clinical course after the
      emergence of viral resistance is variable but still may lead to disease
      progression and graft failure. Analogous to the success of combination therapies
      to delay the emergence of antiviral-resistant HIV, it will be important to
      combine anti-HBV agents with additive or synergistic antiviral properties and
      different resistance profiles for future de novo combination therapies for
      hepatitis B infection.

PMID- 11512521
TI  - Does resistance to apoptosis affect clinical response to antitumor drugs?

PMID- 11512522
TI  - Apoptosis is critical for drug response in vivo.

PMID- 11512523
TI  - Apoptosis: mediator or mode of cell killing by anticancer agents?

PMID- 11512524
TI  - Resistance as a tool in the study of old and new drug targets in Toxoplasma.
AB  - Drug resistance generated in vitro in the protozoan parasite Toxoplasma gondii is
      described. We focus on drugs that are in use in patients, that show some promise
      for such use, or that represent lead compounds for further development. No
      instance has yet been reported where resistance to any of these drugs has arisen
      in a patient or in the field although different strains do show varying degrees
      of sensitivity. For many of these drugs, however, resistant lines have been
      generated in the laboratory and these have proven very useful for elucidating a
      given drug's target. These targets range from metabolic pathways in the cytosol
      to organellar functions encoded in the mitochondrion or plastid. Such information
      makes predictions about how fast resistance will arise in the field but more
      importantly, it helps identify targets that are crucial to the parasite and
      predicts which combinations of drugs should act synergistically.

PMID- 11512525
TI  - Mitochondria as targets for established and novel anti-cancer agents.
AB  - Chemoresistant cells have acquired the ability to evade the action of multiple
      classes of anti-neoplastic compounds. One mechanism by which tumor cells survive
      in the presence of chemotherapy is by increasing their apoptotic threshold. Since
      mitochondria are central players in drug-induced apoptosis, recent efforts to
      eradicate chemorefractory cells have focused on the identification of compounds
      that directly affect mitochondrial function. A number of reports indicate that
      mitochondria are direct targets for multiple classes of experimental compounds. A
      few clinically available anticancer agents like DNA damaging compounds and anti
      microtubule agents are also reported to act directly on mitochondria. The purpose
      of this mini-review is to discuss recent advances in the interactions between
      anti-cancer agents and mitochondria, and highlight potential mitochondrial
      targets for novel chemotherapeutic interventions.

PMID- 11512527
TI  - Proceedings of the 4th Asian Congress for Microcirculation. Bandung, Indonesia,
      25-27 February 2000.

PMID- 11512526
TI  - Low-level antibacterial resistance: a gateway to clinical resistance.
AB  - The huge amount of antibiotic substances released in the human environment has
      probably resulted in an acceleration in the rate of bacterial evolution. It is to
      note that most interactions between chemotherapeutic agents and microbial
      populations occur at very low antibiotic concentrations. Thus, natural selection
      is expected to act on very small increases in the bacterial ability to resist to
      antibiotic inhibitory effects. On the other hand, there is a wealth of mechanisms
      to resist to these low antibiotic concentrations. The progressive enrichment in
      low-level resistant populations favours secondary selections for more specific
      and effective mechanisms of resistance, particularly in treated patients. These
      adaptations may have a biological cost in the absence of antibiotics, but
      frequently compensatory mutations occur, minimizing such genetic burden. In this
      way, a phenomenon of directional selection takes place, with low possibilities of
      return to susceptibility. Moreover, low antibiotic concentrations are not only
      able to select low-level antibiotic resistant variants, but may produce a
      substantial stress in bacterial populations, that eventually influences the rate
      of genetic variation and the diversity of adaptive responses. More attention
      should be devoted to the mechanisms of low-level resistance in microorganisms, as
      they can serve as stepping stones to develop high level, clinically relevant
      resistance. These mechanisms should be identified early in the development of
      drugs in order to adapt the therapeutic strategies (for instance dosage) to
      minimize the selection of low-level resistant variants, as frequently they emerge
      by means of concentration-specific selection. At the same time, conventional
      susceptibility testing should probably be able to detect low-level resistance,
      and not only clinically-relevant resistance. We should be vigilant of the
      evolutionary trends of microorganisms; for that a purpose, knowledge of the
      biology and epidemiology of low-level resistance is becoming a real need.

PMID- 11512528
TI  - A comparative study of clarithromycin modified release and amoxicillin/clavulanic
      acid in the treatment of acute exacerbation of chronic bronchitis.
AB  - This phase III, investigator-blind, randomized, parallel-group study compared the
      efficacy and tolerability of clarithromycin modified release (MR) with those of
      amoxicillin/clavulanic acid in 250 adult outpatients with acute exacerbationof
      chronic bronchitis (AECB). Patients received either clarithromycin MR 500 mg once
      daily or amoxicillin/clavulanic acid 500 mg/125 mg three times daily for 7 days.
      Primary endpoints were sponsor-defined clinical response and pathogen outcome at
      the end of treatment. Secondary endpoints were sponsor-defined clinical response
      and pathogen outcome at study end, investigator-defined clinical response at end
      of treatment and end of study, resolution or improvement of signs and symptoms,
      eradication of baseline pathogens, serologic outcome for atypical pathogens, and
      occurrence of reinfection and superinfection. Adverse events and compliance were
      also evaluated. Clinical and bacteriologic outcomes with both treatments for all
      endpoints were statistically equivalent, as were total adverse events, although
      the incidences of digestive disturbances (13% vs 4%) and discontinuations due to
      adverse events (8 vs 2 patients; P < or =.05) were significantly higher with
      amoxicillin/clavulanic acid. Ninety-five percent of patients receiving
      clarithromycin MR and 80% receiving amoxicillin/clavulanic acid were 100%
      compliant with medication (P < or =.05). Clarithromycin MR and
      amoxicillin/clavulanic acid are both well tolerated and effective as therapy for
      AECB; however, clarithromycin produced fewer side effects and discontinuations
      and higher compliance rates.

PMID- 11512529
TI  - Outcomes after posterolateral lumbar fusion with instrumentation in patients
      treated with adjunctive pulsed electromagnetic field stimulation.
AB  - Fusion success and clinical outcome were determined in 48 high-risk patients who
      underwent posterolateral lumbar fusions with internal fixation and were treated
      with adjunctive pulsed electromagnetic field (PEMF) stimulation postoperatively.
      An independent radiographic assessment demonstrated a success rate of 97.9%.
      Following treatment, 59% of the working patients returned to their employment.
      Overall clinical assessment was excellent in 4.2% of patients, good in 79.2%, and
      fair in 16.7%; no patient had a poor clinical assessment.

PMID- 11512530
TI  - Population-based screening with the Coronary Heart Disease Risk Factor
      Calculator.
AB  - Data from the Framingham Heart Study and risk-appraisal models were used to
      develop a Coronary Heart Disease (CHD) Risk Factor Calculator for early
      identification of high-risk individuals. The Calculator was tested at an employee
      health fair for a large northeastern US corporation. Of the 590 employees who
      registered for cholesterol screening, 514 had their CHD risk calculated, and 134
      (26.1%) of this group had a relative risk greater than 2. Elevated risk increased
      with age, ranging from 26.2% of those younger than 35 years to 75% of the over-64
      group. Of special concern was the percentage of individuals below 45 years of age
      whose relative risk of CHD in the next 10 years was more than twice that of
      coevals with standard risk. The program also estimates and visually demonstrates
      possible benefits of interventions, allows monitoring of progress, and serves as
      an educational aid to motivate behavior modification. In this test, the software
      functioned as designed, and graphic demonstration of individual risk estimations
      appeared to motivate several participants to seek medical follow-up.

PMID- 11512531
TI  - Comparing phytopharmaceuticals: the example of St. John's Wort.
AB  - At present, dosage in phytotherapy often falls victim to an undifferentiated
      point of view. In the case of St. John's Wort, for example, 900 mg of extract has
      become the standard dosage; however, no studies have investigated the dose-effect
      ratio, even though there are numerous indications that smaller amounts,
      particularly of ethanolic extracts, are sufficient to achieve the desired effect.
      Moreover, listing extract dosages is of no use unless other identifying
      characteristics are also specified. If phytopharmaceuticals are to be compared
      with one another, the scope of consideration cannot be limited to single
      components. The comparison must be carried out comprehensively.

PMID- 11512532
TI  - Herbal medicine in pregnancy and childbirth.
AB  - Pregnant women often use medicinal herbs in an effort to maintain good health and
      reduce the need for medical intervention. A survey of the scientific and popular
      literature identified a number of therapeutic herbs used in North America. Three
      categories are discussed: tonics, herbs for preventing miscarriage, and herbs for
      inducing labor. Some of these preparations may address women's needs in ways that
      biomedicine has failed to do. Purported merits and hazards of these medications
      are discussed.

PMID- 11512533
TI  - Suicide Prevention 2000. Proceedings of a conference. May 7-8, 2000. New York
      City, New York, USA.

PMID- 11512534
TI  - Unity of Knowledge: The Convergence of Natural and Human Science. Proceedings of
      a conference. New York City, New York, USA. June 23-25, 2000.

PMID- 11512535
TI  - The treatment of depression: a consumer report.

PMID- 11512536
TI  - Heart lines. Revised cholesterol guidelines.

PMID- 11512537
TI  - [Community acquired pneumonia].

PMID- 11512538
TI  - Cephalosporins: The Golden Jubilee, 1948-1998. Cagliari, Italy, 11-13 December
      1998.

PMID- 11512540
TI  - The Artificial Pancreas Symposium: glucose monitoring, insulin delivery, feedback
      control.

PMID- 11512541
TI  - The UCSF Diabetes Symposium: Research Breakthroughs in Diabetes.

PMID- 11512542
TI  - Trends in antimicrobial resistant staphylococci in an university hospital over a
      6-year period.

PMID- 11512543
TI  - A pharmacist on your belt.

PMID- 11512544
TI  - CDC claims to identify the unknown infected.

PMID- 11512545
TI  - Skin, the final frontier.

PMID- 11512546
TI  - Another comment on the role of statistical methods.

PMID- 11512547
TI  - Cellular changes following uterine artery embolization for the treatment of
      adenomyosis.

PMID- 11512548
TI  - Cervical cytology EQA--the Northern experience.

PMID- 11512549
TI  - Cervical cytology EQA--the Northern experience.

PMID- 11512550
TI  - Quantitative cytological analysis of smears collected from lesions clinically
      resembling oral lichen planus.

PMID- 11512551
TI  - Cholecystocholedocholithiasis: the difficult relationship between ERCP and
      laparoscopic cholecystectomy.

PMID- 11512552
TI  - Characteristic endosonographic features of gastric inflammatory fibroid polyps.

PMID- 11512553
TI  - Toxicologic causes of giggling.

PMID- 11512554
TI  - Single question screening for problem drinking.

PMID- 11512555
TI  - [Palliative medicine. Editorial].

PMID- 11512556
TI  - Re.: Impending serious crisis in neuroradiology.

PMID- 11512557
TI  - Haplotype analysis of BRCA2 8765delAG mutation carriers in French Canadian and
      Yemenite Jewish hereditary breast cancer families.
AB  - The BRCA2 8765delAG mutation was previously reported in hereditary breast cancer
      families of French Canadian and Yemenite Jewish descent. Haplotype analysis,
      using six microsatellite markers that span BRCA2 and two intragenic
      polymorphisms, was performed on 8765delAG mutation carriers to determine if there
      was evidence that the mutations were identical by descent. The alleles of the
      microsatellite markers most closely flanking BRCA2 (D13S1697 and D13S1701) were
      found to be identical in state in all the mutation carriers. However, the disease
      associated allele of one of the intragenic markers differed between the Yemenite
      Jews and French Canadian families, indicating that the 8765delAG mutation has
      independent origins in these two geographically and ethnically distinct
      populations.

PMID- 11512559
TI  - Abstracts of the 14th International Chromosome Conference. Wurzburg, Germany, 4-8
      September 2001.

PMID- 11512558
TI  - Annual Meeting of the American Academy of Otolaryngology--Head and Neck Surgery
      Foundation, Inc. Denver, Colorado, USA. September 9-12, 2001. Abstracts.

PMID- 11512560
TI  - Directory of the top 21 CM credentials.

PMID- 11512561
TI  - Anesthetic induction agents, sympathetic nerve activity and baroreflex
      sensitivity: a study in rabbits comparing thiopental, propofol and etomidate.
AB  - The mechanisms of arterial hypotension following intravenous anesthetic induction
      agents are multifactorial. The purpose of this study was to evaluate and compare
      the effects of thiopental, propofol and etomidate on hemodynamics, sympathetic
      outflow and arterial baroreflex sensitivity using not only neuraxis-intact but
      also totally baro-denervated rabbits. A total of 60 rabbits was anesthetized with
      urethane, tracheotomized, and mechanically ventilated with oxygen in nitrogen
      (FiO2 0.5). The left renal sympathetic nerve was isolated and placed on a bipolar
      electrode to record renal sympathetic nerve activity (RSNA). Thirty animals
      underwent a surgical preparation of total baroreceptor denervation. Bolus
      injections of an anesthesia induction dose of thiopental 4 mg/kg and twice the
      induction dose of propofol 4 mg/kg significantly decreased RSNA to the same
      extent (19.4+/-6.7 and 19.7+/-5.2% reduction, mean +/- SEM) and mean arterial
      pressure (MAP) also to the same extent (19.5+/-4.6 and 22.1+/-3.1% reduction) in
      the neuraxis-intact animals. RSNA was increased (34.5+/-6%) without reduction of
      MAP by an induction dose of etomidate, 0.3 mg/kg. Sympathetic barosensitivity was
      attenuated even 10 min after thiopental at 4 mg/kg or propofol at 4 mg/kg (68%
      and 54% of control, respectively). Propofol at 2 mg/kg (induction dose) and
      etomidate at 0.6 mg/kg decreased RSNA and MAP only in the baro-denervated
      animals. It was found from the barosensitivity study that patients can be
      hemodynamically unstable even though blood pressure has returned to normal after
      thiopental and propofol administration. Data suggest that etomidate can even
      stimulate the sympathetic nervous system and increase sympathetic outflow. It was
      also clearly found from the baro-denervated animal study that thiopental was
      stronger than propofol in directly suppressing sympathetic outflow at the
      induction dose.

PMID- 11512562
TI  - Intercellular adhesion molecule-1 in patients with idiopathic interstitial
      pneumonia.
AB  - This study focuses on a possible role of intercellular adhesion molecule-1 (ICAM
      1) in interstitial pulmonary diseases. We determined a soluble form of ICAM-1 in
      serum and bronchoalveolar lavage fluid (BALF) using ELISA in patients with usual
      interstitial pneumonia (UIP), bronchiolitis obliterance organizing pneumonia
      (BOOP), or nonspecific interstitial pneumonia (NSIP). In addition, we
      investigated the expression of ICAM-1 in the lung tissues of these patients by
      means of immunohistochemical staining. Serum levels of soluble ICAM-1 were
      significantly higher in patients with UIP or NSIP than in healthy subjects, and
      were also high in patients with BOOP. The soluble ICAM-1 in BALF tended to be
      higher in patients with UIP, BOOP, or NSIP than in normal subjects. A significant
      correlation was seen between soluble levels of ICAM-1 in serum and BALF. In the
      immunostaining of ICAM-1 of the lung tissues, ICAM-1 expression was more
      pronounced in patients with UIP than in those with BOOP or NSIP. The increased
      expression of ICAM-1 was seen in type II alveolar epithelium and vascular
      endothelium in patients with interstitial pneumonia. A positive correlation was
      observed between the degree of ICAM-1 expression in the lung tissues and the BALF
      levels of soluble ICAM-1. The expression of ICAM-1 in type II alveolar epithelium
      suggests that ICAM-1 plays a specific role in the fibrotic process of the lung,
      and that the measurement of soluble ICAM-1 in sera and BALF could be a useful
      marker for evaluating the progression of fibrosis.

PMID- 11512563
TI  - Non-invasive evaluation of the adaptations of cardiac function in the neonatal
      period: a comparison of healthy infants delivered by vaginal route and caesarean
      section.
AB  - Postnatal adaptations of cardiac hemodynamics in infants born vaginally or by
      caesarean section may be different. These cardiac functions were evaluated by
      Doppler echocardiography to assess adaptation differences. Cardiac output, heart
      rate, stroke volume, mean arterial pressure, total systemic vascular resistance,
      ejection fraction, and ductus arteriosus diameter were determined and compared at
      1, 24 and 72 h of life in 22 infants born vaginally (group 1) and 23 born by
      caesarean section (group 2). One hour after delivery, heart rate, mean blood
      pressure, and total systemic resistance were found to be higher in group 1
      infants (P < 0.01, P < 0.05, P < 0.05 respectively). Stroke-volume measurements
      were significantly higher in group 2 (P < 0.05). The ejection fraction and
      cardiac output values were similar in both groups. At 24 and 72 h, no significant
      differences were observed in measurements of infants born vaginally or by
      caesarean section. We did not find a parameter negatively affecting healthy
      newborns in either mode of delivery. However, under pathological conditions
      affecting the cardiovascular system at 1 h of life, including perinatal
      infections and hypoxemia, a lower stroke volume, higher heart rate, higher mean
      blood pressure, and higher peripheral resistance may cause additional work load
      to the cardiovascular system in infants born vaginally.

PMID- 11512564
TI  - Concentration of nitric oxide (NO) in spinal fluid of chronic spinal disease.
AB  - We studied total nitric oxide (nitrite + nitrate) (NO) levels in cerebrospinal
      fluid (CSF) of chronic spinal diseases in nonsmokers (133 patients: 76 men and 57
      women; mean age, 63 years; range, 15-92 years) by the Griess method to clarify
      the role of NO in different spinal diseases. The extent of compression in terms
      of numbers of disc level at the compressed spinal nerve and neurological
      evaluation were also assessed according to the Japanese Orthopaedic Association
      scores. The spinal diseases included cervical myelopathy and radiculopathy
      (cervical disease group), ossification of yellow ligament (thoracic disease
      group), and lumbar disc herniation, lumbar canal stenosis and lumbar
      spondylolisthesis (lumbar disease group). NO levels in the spinal disease groups
      (4.98+/-2.28 micromol/l: mean +/- SD) were significantly higher than that in the
      control group (2.53+/-0.94 micromol/l). An inverse correlation was detected
      between the elevated levels of NO and the grade of clinical symptoms in the
      cervical disorders. The number of disc level at the compressed spinal nerve was
      positively correlated with elevated NO levels in CSF in the cervical and lumbar
      disorder groups. These results indicate that nerve compression may elevate NO
      levels in CSF, and that NO concentration in the CSF might be a useful marker of
      damage to nervous system in spinal disorders.

PMID- 11512565
TI  - Cold activation of serum complement in patients with chronic hepatitis C: study
      on activating pathway and involvement of IgG.
AB  - It has been documented that the serum complement activities measured by hemolytic
      assay (CH50) are decreased after storage of sera at a low temperature in some
      patients with chronic hepatitis C. However, the mechanism of this phenomenon has
      not been identified yet. Here, we tried to elucidate factors involved in the cold
      activation of complement (CAC). To clarify what pathway is activated in CAC, we
      measured complement cleavage products after cold storage of sera. C4d increased
      significantly after 12 h-storage at cold temperatures in 5 CAC (+) sera compared
      with 5 CAC (-) (P < 0.01) and 3 control sera (P < 0.05), while Bb did not
      increase in any of the groups. In order to determine whether IgG or IgG complex
      is necessary for CAC, 8 CAC (+) sera were incubated with Protein G Sepharose gel
      beads, and all of them retained hemolytic activities to some extent after cold
      storage. Column chromatography through Superose 6HR of CAC-positive serum
      identified the fractions containing molecules that induced CAC in normal serum,
      which were depleted by treatment with protein G Sepharose. In conclusion, CAC in
      hepatitis C seems to occur via a classical or lectin pathway, and the IgG complex
      produced in hepatitis C virus infection may be an important factor in inducing
      CAC, a common extrahepatic manifestation of hepatitis C.

PMID- 11512566
TI  - Kinematic magnetic resonance imaging (MRI) of the normal shoulder: assessment of
      the shapes and signals of the superior and inferior labra with abductive movement
      using an open-type imager.
AB  - A preliminary study was conducted to evaluate the superior and inferior glenoid
      labra with abductive movement using an open-type MR unit in asymptomatic healthy
      volunteers. Both fast low angle shot (FLASH) and turbo spin echo (TSE) images
      were obtained to evaluate the shapes of both the superior and inferior labra, as
      well as to assess changes in signal at these sites. As the abduction angle was
      increased, the shape of the superior labrum changed from round or triangular to
      crescentic and a higher signal was frequently seen. At an abduction angle of 150
      degrees, an increase in signal was seen in one-half of the superior labra; this
      increase was noted more frequently in volunteers over 40 years of age. In some of
      the superior labra, the increase in signal seen at 150 degrees abduction
      disappeared on subsequent images obtained at 0 degrees abduction. Hence, the
      increase in signal was considered to be a reversible change. The shape of the
      inferior labrum tended to change from crescentic to triangular or round. An
      increase in signal in the inferior labrum was unrelated to the abduction angle.
      Abductive kinematic studies using an open-type MR unit provides information about
      the morphology of the superior and inferior labra, as well as information about
      signal changes occurring at these sites.

PMID- 11512567
TI  - Significance of adrenomedullin under cardiopulmonary bypass in children during
      surgery for congenital heart disease.
AB  - To elucidate the effect of adrenomedullin (AM) on fluid homeostasis under
      cardiopulmonary bypass (CPB), we investigated the serial changes in plasma AM and
      other parameters related to fluid homeostasis in 13 children (average age, 28.2
      months) with congenital heart disease during cardiac surgery under CPB. Arterial
      blood and urine samples were collected just after initiation of anesthesia, just
      before commencement of CPB, 10 min before the end of CPB, 60 min after CPB, and
      24 h after operation. Plasma AM levels increased significantly 10 min before the
      end of CPB and decreased 24 h after operation. Urine volume increased transiently
      during CPB, which paralleled changes in AM. Simple regression analysis showed
      that plasma AM level correlated significantly with urinary vasopressin, urine
      volume, urinary sodium excretion, and plasma osmolarity. Stepwise regression
      analysis indicated that urine volume was the most significant determinant of
      plasma AM levels. Percent rise in AM during CPB relative to control period
      correlated with that of plasma brain natriuretic peptide (r = 0.57, P < 0.01).
      Our results suggest that AM plays an important role in fluid homeostasis under
      CPB in cooperation with other hormones involved in fluid homeostasis.

PMID- 11512568
TI  - Successful resection of rectal carcinoma in an Evans' syndrome patient followed
      by predonisolone and high-dose immunoglobulin: report of a case.
AB  - A 69-year-old woman was admitted to our hospital because of anal bleeding and
      fatigue. The patient was previously diagnosed as having Evans' syndrome on the
      basis of hematological examination and had been treated with predonisolone for 8
      years. On admission, severe anemia and thrombocytopenia were noted. Colonoscopy
      and Barium enema studies demonstrated an irregular tumor with hemorrhagic
      ulceration in the rectum, which was histopathologically confirmed as an
      adenocarcinoma. After red blood cells and platelets were transfused, and the
      patient was treated with high-dose gammaglobulin, predonisolone, and camostat
      mesylate, the platelet count gradually increased and hemolysis was well
      controlled. The patient then underwent Hartmann's operation and splenectomy
      without any postoperative complications. Predonisolone and high-dose
      immunoglobulin therapy in a rectal cancer burdened patient with Evans' syndrome
      is considered useful in combination with surgical treatment. This is the first
      case report of rectal carcinoma resection in a patient with Evans' syndrome.

PMID- 11512569
TI  - Fracture of the penis: treatment and complications.

PMID- 11512570
TI  - Japan collaborative cohort study for evaluation of cancer risk sponsored by
      monbusho (JACC study).
AB  - This paper primarily aimed to overview the rationale for initiating the Japan
      Collaborative Cohort Study for Evaluation of Cancer Risk Sponsored by Monbusho
      (Ministry of Education, Science, Sports and Culture of Japan) (JACC Study), by
      comparing socio-demographic and nutritional changes that were witnessed between
      1965 and 1990 in Japan, and also to describe the study design, the follow-up
      conditions as of the end of 1997, and the frameworks for analyzing the data of
      the lung, stomach, pancreas and gallbladder/bile duct, based on the approximately
      8-year follow-up data. For other major sites such as cancers of the large
      intestine and liver, an analysis will be started in the fiscal year of 2002. This
      paper secondarily aimed to be cited as the basic information on the JACC Study
      when several publications are to be based on.

PMID- 11512571
TI  - Age-period-cohort analysis of lung cancer mortality in Japan, 1960-1995.
AB  - The mortality data on lung cancer in Japan from 1960 to 1995 was analysed based
      on an age-period-cohort (APC) model. Though the APC model has an 'identifiable
      problem' caused by the relationship of age, period and cohort parameters, non
      linear components of them revealed their original (separated) effects. They were:
      (1) non-linear age effects had a peak in 55-59 and 60-64 years old in males and
      50-54 in females, (2) non-linear period effects were very small in both genders,
      (3) non-linear age and period effects were small enough to neglect compared with
      their linear effects, and (4) there were five parts of trends in Japanese lung
      cancer mortality in both genders in the non-linear birth cohort effects. The 1961
      65 birth cohort effect seemed to increase differently from previous birth years.
      This trend should be monitored carefully.

PMID- 11512572
TI  - Relationship between having a home doctor and outpatient utilization.
AB  - While universal insurance coverage should eliminate or substantially reduce
      financial and certain structural barriers to medical care, inequity in
      utilization of care may continue to exist. We conducted a questionnaire survey of
      a national random sample of 4500 Japanese age 16 or over in October, 1995.
      Separate analyses were conducted to predict the physician visit rates for the
      entire respondents (N=3395) and for those with chronic conditions (N=777). Forty
      three percent of the total subjects reported an ambulatory physician visit within
      the past three months. About 17% of subjects with one chronic condition and 14%
      of those with two or more chronic conditions did not have any physician visits
      within recent three months. The regression model demonstrated that having a home
      doctor, as well as comorbidity and perceived health status, is significantly
      associated with outpatient visit both among all subjects (p < 0.0001) and among
      those with chronic conditions (p < 0.01). The Japanese health system still has
      unevenness in outpatient resource utilization. This mainly pertains to whether
      they have their own regular physician. The failure of some persons with chronic
      diseases to be seen requires further investigation.

PMID- 11512573
TI  - Regression analysis of cancer incidence rates and water fluoride in the U.S.A.
      based on IACR/IARC (WHO) data (1978-1992). International Agency for Research on
      Cancer.
AB  - Age-specific and age-standardized rates (ASR) of registered cancers for nine
      communities in the U.S.A. (21.8 million inhabitants, mainly white) were obtained
      from IARC data (1978-82, 1983-87, 1988-92). The percentage of people supplied
      with "optimally" fluoridated drinking water (FD) obtained from the Fluoridation
      Census 1985, U.S.A. were used for regression analysis of incidence rates of
      cancers at thirty six sites (ICD-WHO, 1957). About two-thirds of sites of the
      body (ICD) were associated positively with FD, but negative associations were
      noted for lip cancer, melanoma of the skin, and cancers of the prostate and
      thyroid gland. In digestive organs the stomach showed only limited and small
      intestine no significant link. However, cancers of the oral cavity and pharynx,
      colon and rectum, hepato-biliary and urinary organs were positively associated
      with FD. This was also the case for bone cancers in male, in line with results of
      rat experiments. Brain tumors and T-cell system Hodgkin's disease, Non-Hodgkin
      lymphoma, multiple myeloma, melanoma of the skin and monocytic leukaemia were
      also correlated with FD. Of the 36 sites, 23 were positively significant (63.9%),
      9 not significant (25.0%) and 4 negatively significant (11.1%). This may indicate
      a complexity of mechanisms of action of fluoride in the body, especially in view
      of the coexising positive and negative correlations with the fluoridation index.
      The likelihood of fluoride acting as a genetic cause of cancer requires
      consideration.

PMID- 11512574
TI  - Renal tubular dysfunction in male inhabitants of a cadmium-polluted area in
      Toyama, Japan--an eleven-year follow-up study.
AB  - An eleven-year follow-up study was carried out to elucidate the changes in the
      level of environmental exposure to cadmium (Cd) from rice after soil replacement
      of polluted paddy fields and these effects on urinary excretion of Cd in male
      inhabitants of a Cd-polluted area in Toyama, Japan. In addition, the prevalence
      of renal tubular dysfunction (RTD) was examined to clarify the progress of Cd
      induced RTD. One hundred and twenty-seven male inhabitants born between 1914 and
      1929 in 11 districts of the Cd-polluted Jinzu River basin and 31 reference
      subjects in 2 adjacent districts were examined twice in 1985-86 and 1996-97. The
      geometric means of Cd concentrations in polished rice (Cd-R) in the Cd-polluted
      areas were 0.18 ppm in 1985 and 0.21 ppm in 1986; these values were significantly
      higher than those of the reference areas (0.13 ppm in 1985 and 0.12 ppm in 1986).
      After 11 years, the Cd-R levels were significantly decreased to approximately
      half (0.08 ppm in 1996, 0.12 ppm in 1997) due to soil replacement of polluted
      paddy fields, which has been carried out since 1980. The mean Cd levels in urine
      (Cd-U) were significantly reduced from 7.9 and 9.5 microg/g creatinine in the
      initial study to 6.9 and 6.8 microg/g creatinine in the follow-up study. However,
      the prevalence of RTD, which was determined by urinary beta2-microglobulin
      exceeding 1 mg/g creatinine and urinary glucose exceeding 150 mg/g creatinine,
      increased from 18 and 23% in the 1985-86 study to 25 and 32% in the 1996-97
      study, and a total of 12 new cases (12%) of RTD were found. Whereas, only one
      subject (4%) in the reference control areas was identified as RTD. Cd-induced RTD
      was prevalent, progressive and irreversible for male inhabitants of the Cd
      polluted Jinzu River basin, although the environmental exposure to Cd through
      rice was significantly reduced by soil replacement of polluted paddy fields.

PMID- 11512575
TI  - Long-term blood pressure variability and cerebrovascular changes on CT in a
      community-based elderly population.
AB  - The effects of long-term blood pressure (BP) levels on cerebrovascular changes
      were analyzed in a community-based healthy elderly population. Cranial computed
      tomography (CT) was performed for 300 residents aged 69 years and older. Long
      term BP during the ten years prior to CT was assessed, and the cerebrovascular
      changes were compared among different patterns of long-term blood pressure
      variability. White matter lesions (WML) and/or silent infarctions (SI) were found
      in 73 subjects (23.6%). Multiple logistic regression analysis showed that
      subjects with long-term diastolic hypertension (DHT) had the highest risk of
      cerebrovascular changes (adjusted odds ratio (OR), 95% confidence interval (CI);
      7.1, 2.4-21.6, for WML; 7.2, 2.7-19.4, for SI), and that long-term isolated
      systolic hypertension (ISHT) was significantly associated with SI (adjusted OR,
      95%CI, 2.3, 1.1-4.9), but not with WML (adjusted OR, 95%CI, 1.3, 0.5-3.3).
      Efforts to prevent both DHT and ISHT would be beneficial, though different
      underlying mechanisms for WML and SI were suggested.

PMID- 11512576
TI  - Factors related to biomedical research productivity in Asian countries.
AB  - By and large, biomedical research is not a priority sector in Asian countries due
      to many factors. Lack of resources and trained manpower are certainly among these
      factors. We investigated the factors related to biomedical research productivity
      in Asian countries based on Medline data. The number of biomedical articles
      published in the indexed journals from each country of Asia and Oceania during
      1990-1998 was used as a surrogate of total biomedical research productivity.
      Multiple regression analysis revealed that low gross national product per capita
      (p<0.013), insufficient number of physicians (p<0.047), and inadequate public
      spending on the health sector (p<0.049) were responsible for the meager number of
      biomedical publications in Asian countries.

PMID- 11512577
TI  - The value of b required to avoid T2 shine-through from old lucunar infarcts in
      diffusion-weighted imaging.
AB  - Multiple small infarcts of different ages are common in small-vessel disease.
      Diffusion-weighted imaging (DWI) is a powerful method for discriminating new from
      chronic lesions. This can be done on the diffusion-weighted images provided that
      b is sufficiently high. Our purpose was to determine that critical value of b. We
      reviewed DWI from a previous study of acute, mainly lacunar strokes, and selected
      18 old lacunar infarcts, well defined on uncoded images with b 0 s/m2 (i. e., T2
      weighted images) but invisible on DWI with b 1,200 x 10(6) s/m2. We used a 1.5
      tesla imager and single-shot echo-planar technique. We had seven separate
      acquisitions with echo time 123 ms and b in steps between 0 and 1,200 x 10(6)
      s/m2. Two neuroradiologists blinded to the selection of lesions carried out two
      different lesion-detection procedures, thereby testing each lesion four times,
      giving a total of 72 tests of b values. The results were consistent, indicating a
      level for detection of 800 x 10(6) s/m2 in two tests, 400-600 x 10(6) s/m2 in 65
      tests and at lower values in the remainder. For imagers up to 1.5 tesla, at long
      repetition times and an echo time up to 120 ms T2-shine through of old lacunar
      infarcts can be avoided using b of 1,000 x 10(6) s/m2.

PMID- 11512578
TI  - Does the "keyhole" technique improve spatial resolution in MRI perfusion
      measurements? A study in volunteers.
AB  - We examined the potential of the 'keyhole' technique to improve spatial
      resolution in perfusion-weighted MRI on whole-body imagers with standard gradient
      hardware. We examined 15 healthy volunteers. We acquired a high-resolution image
      with 256 phase-encoding steps before a bolus-tracking procedure. For the dynamic
      series we collected only 34 lines in the center of k-space. Data reconstruction
      was performed by both zero-filling and keyhole methods. The dynamic datasets,
      concentration-time curves calculated from user-defined regions and maps of the
      cerebrovascular parameters using both reconstruction methods were compared. Using
      keyhole series, anatomical structures could easily be defined which were not seen
      on the original dynamic series because of blurring due to ringing artefacts.
      Comparison of signal-time curves in large regions yielded no significant
      difference in signal loss during bolus passage. In the parameter maps truncation
      artefacts were significantly reduced using keyhole reconstruction. The keyhole
      method is appropriate for enhancing image quality in perfusion-weighted imaging
      on standard imagers without sacrificing time resolution or information about
      transitory susceptibility changes. However, it should be applied carefully,
      because the spatial resolution of the dynamic signal change and the
      cerebrovascular parameters is less than that afforded by the spatial resolution
      of the reconstructed images.

PMID- 11512579
TI  - In vivo proton MR spectroscopy of chorea-ballismus in diabetes mellitus.
AB  - The most common cause of chorea-ballismus (CB) is a vascular lesion; it is also
      associated with nonketotic hyperglycaemia in diabetes mellitus (DM) and may be
      the first manifestation of this disorder. We describe the CT, MRI and proton MR
      spectroscopy (1H-MRS) of CB in eight patients. Six had hemichorea-hemiballismus
      (HC-HB) and two bilateral CB. Single-voxel (SV) 1H-MRS was performed using point
      resolved spectroscopy (PRESS). Voxels were positioned in the basal ganglia of the
      patients and control subjects. PRESS was also used to obtain spectroscopic
      imaging (1H-MRSI) of the slice of interest in two patients. CT showed a slightly
      dense striatum in all the patients with CB, and T1-weighted images revealed high
      signal. The CB correlated well with the neuroimaging findings. SV 1H-MRS showed
      the mean (+/- SD) N-acetylaspartate (NAA)/ creatine (Cr) ratio to be 1.45 +/-
      0.19 in HC-HB and 1.82 +/- 0.06 on the opposite normal side (P = 0.01). The
      choline (Cho)/ Cr ratio was 1.3 +/- 0.12 in HC-HB and 1.11 +/- 0.13 on the
      opposite normal side (P = 0.005). A lactate peak was seen in seven patients. The
      NAA/Cr ratio was 1.44 +/- 0.15 in bilateral CB and 1.74 +/- 0.16 in the controls
      (P = 0.017); the Cho/Cr ratios were 1.36 +/- 0.1 and 1.19 +/- 0.07 (P = 0.015).
      The low NAA/Cr suggests neuronal loss or damage and the high Cho/Cr probably
      indicates gliosis. The presence of lactate may suggest mild ischaemia due to
      acute vascular events during hyperglycaemia and underlying chronic focal
      cerebrovascular diseases in DM.

PMID- 11512580
TI  - Proton MR spectroscopy in idiopathic spasmodic torticollis.
AB  - Single-voxel proton magnetic resonance spectroscopy (1H-MRS), localised to the
      basal ganglia, was used to determine changes in metabolite levels in idiopathic
      spasmodic torticollis (IST). We examined nine patients and 13 healthy subjects.
      The mean values (+/- SD) of peak area ratios were: IST: N-acetyl-aspartate
      (NAA)/choline-containing compounds (Cho) 1.79 +/- 0.39, NAA/creatine and
      phosphocreatine compounds (Cr) 1.61 +/- 0.38, Cho/Cr 0.91 +/- 0.19; controls:
      NAA/Cho 2.07 +/- 0.35, NAA/ Cr 1.82 +/- 0.31, Cho/Cr 0.89 +/- 0.12. Statistical
      analysis showed that NAA/Cho and NAA/Cr were significantly lower in patients than
      in controls (P = 0.0304 and 0.0431, respectively). These results indicate a
      reduction in NAA, and suggest striatal involvement in the pathogenesis IST.

PMID- 11512581
TI  - Decrease in N-acetylaspartate/creatine ratio in the motor area and the frontal
      lobe in amyotrophic lateral sclerosis.
AB  - We studied whether N-acetylaspartate (NAA), a neuronal marker, is reduced in the
      brain of 14 patients with clinically definite amyotrophic lateral sclerosis (ALS)
      and whether NAA levels in the motor area and frontal lobe correlate with the
      clinical features, including frontal lobe function. We also studied 14 normal
      controls were evaluated. We obtained peak integrals in 1H magnetic resonance
      spectroscopy (MRS) for NAA, creatine (Cr), and choline-containing compounds
      (Cho). Severity of the disease was determined using the manual muscle strength
      test, and the Norris limb and bulbar scales. In the patients, the NAA/Cr ratio
      was reduced in the motor area and frontal lobe, while the Cho/Cr ratio was normal
      throughout the brain. There were significant correlations between the NAA/Cr
      ratio in the motor area and the Norris limb scale (r = 0.50; P < 0.01) and
      between the NAA/Cr ratio in the frontal lobe and the number of categories
      achieved in the Wisconsin Card Sorting test (r = 0.71; P < 0.05), implying
      frontal lobe dysfunction. These correlations suggest that a reduced NAA/Cr ratio
      is a marker of cortical neuronal loss and dysfunction in ALS.

PMID- 11512582
TI  - Magnetisation transfer measurements of the subcortical grey and white matter in
      Parkinson's disease with and without dementia and in progressive supranuclear
      palsy.
AB  - We measured the magnetisation transfer ratio (MTR) in the subcortical grey and
      white matter of 11 patients with idiopathic Parkinson's disease (PD) without
      dementia, six with PD with dementia (PDD), six with progressive supranuclear
      palsy (PSP), and 12 elderly control subjects to assess regional differences in
      structural brain damage. There were no significant differences in MTR in any
      region between PD and controls. However, patients with PDD had significantly
      lower MTR in the subcortical white matter, including the frontal white matter and
      the genu of the corpus callosum than the controls, whereas PSP had significantly
      lower MTR in the subcortical grey matter, including the putamen, globus pallidus
      and thalamus, in addition to the subcortical white matter. This suggests that
      regional patterns of structural brain damage can be detected using the
      magnetisation transfer technique. Measurement of MTR in the subcortical grey and
      white matter may be useful in differential diagnosis.

PMID- 11512583
TI  - Demonstration of the postcommissural fibres of the fornix in short-inversion time
      inversion-recovery imaging on a high-field system.
AB  - Short-inversion time inversion-recovery (STIR) imaging using a 3 tesla system was
      assessed to reveal the postcommissural fibres (PF) of the fornix, which have
      rarely been highlighted neuroradiologically in the clinical setting. We studied
      27 normal subjects. Sequence parameters were TR/TE/TI 8000/52/ 150 ms. STIR was
      expected to take advantage of the high signal-to-noise ratio of a high-field
      system, due to the long repetition time. PF were identifiable in axial and
      coronal slices in all cases. They were bordered anteriorly and superiorly by the
      anterior commissure and posteriorly and inferiorly by the mamillary body. Behind
      the anterior commissure, they ran in an arch-shaped posterior and inferior course
      in the hypothalamic nuclei and joined the mamillary body anterolaterally. They
      usually extended through three 3-mm slices (with 1 mm interslice gap) in
      anteroposterior and vertical dimensions. Little variation was observed in their
      course or size. Demonstration of the PF would provide a more detailed correlation
      of human neuroanatomy to hypothalamic function and individualised understanding
      of hypothalamic pathology and influence therapy.

PMID- 11512584
TI  - Acute hepatic encephalopathy with diffuse cortical lesions.
AB  - Acute hepatic encephalopathy is a poorly defined syndrome of heterogeneous
      aetiology. We report a 49-year-old woman with alcoholic cirrhosis and hereditary
      haemorrhagic telangiectasia who developed acute hepatic coma induced by severe
      gastrointestinal bleeding. Laboratory analysis revealed excessively elevated
      blood ammonia. MRI showed lesions compatible with chronic hepatic encephalopathy
      and widespread cortical signal change sparing the perirolandic and occipital
      cortex. The cortical lesions resembled those of hypoxic brain damage and were
      interpreted as acute toxic cortical laminar necrosis.

PMID- 11512585
TI  - Postradiation gliosarcoma with osteosarcomatous components.
AB  - A 49-year-old man developed a gliosarcoma with prominent osteoid components 15
      months after surgical resection and postoperative radiation and chemotherapy for
      a right frontal glioblastoma multiforme. The recurrent tumor was distinguished
      from the original lesion by the presence of dense ossification, visible on CT, at
      the original tumor site. The relevant literature is reviewed.

PMID- 11512586
TI  - An intracranial aspergilloma with low signal on T2-weighted images corresponding
      to iron accumulation.
AB  - We present a case of cerebral aspergillosis in an immunocompetent patient. The
      MRI signal characteristics were compared with the histologic findings. Irregular
      low-signal zones were demonstrated between the wall of the abscess and the
      central necrosis on T2-weighted images; the pathology specimen revealed
      concentrated iron in these transitional zones but no hemosiderin. Iron is an
      essential element for the growth of fungal hyphae. The low-signal zones may
      represent the areas where there was active proliferation of aspergillus, and the
      unique location of the low signal may be a helpful imaging characteristic for the
      diagnosis of an aspergillus abscess.

PMID- 11512587
TI  - Divry-Van Bogaert syndrome in a female: relationship to Sneddon's syndrome and
      radiographic appearances.
AB  - A 28-year-old woman presented with generalised livedo reticularis, dementia,
      epilepsy, and pyramidal and extrapyramidal signs. Multiple focal infarcts were
      seen on MRI. Angiography demonstrated widespread cerebromeningeal angiomatosis
      with multiple small and medium size arterial occlusions. A lifelong personal and
      family history of mental handicap in the absence of anticardiolipin antibodies
      suggests Divry-Van Bogaert syndrome, not previously been reported in a female.
      Similarities to Sneddon's syndrome are discussed.

PMID- 11512588
TI  - Intracranial aneurysm associated with relapsing polychondritis.
AB  - We describe a 50-year-old man with relapsing polychondritis (RP) involving
      auricular cartilage, uveitis and hearing loss, who had an aneurysm of the
      anterior cerebral artery. Intracranial aneurysm is a rare manifestation of RP.

PMID- 11512589
TI  - Intramedullary schwannoma of the spinal cord: report of two cases.
AB  - We report magnetic resonance findings in the intramedullary schwannoma of the
      cervical spinal cord in two patients. In both cases, the solid portions of the
      tumours enhanced intensely after administration of Gd-DTPA and the enhanced
      border was sharply delineated from the adjacent spinal cord. Schwannomas should
      be considered in the differential diagnosis of intramedullary tumours when
      magnetic resonance images show a strongly enhancing mass with sharply delineated
      borders.

PMID- 11512590
TI  - Intraspinal epidermoid cyst: diffusion-weighted MRI.
AB  - We report a 7-year-old boy who presented with two-month history of worsening low
      back and right leg pain. Conventional MR images demonstrated a poorly outlined
      intradural mass recognized by the displacement of the conus medullaris and the
      nerve roots of the cauda equina at the L2-3 level. The signal intensity of the
      lesion was similar to CSF There was no contrast enhancement of the lesion.
      Diffusion-weighted images and ADC values revealed restricted diffusion within the
      mass. Myelography confirmed the mass as an intradural filling defect with
      myelographic block at the L2-3 level. The patient underwent total surgical
      excision of the mass. Pathologic examination revealed the diagnosis of epidermoid
      cyst.

PMID- 11512591
TI  - Proton magnetic resonance spectroscopy in disturbances of cortical development.
AB  - Proton magnetic resonance spectroscopy(1H-MRS) can be used for looking at
      cerebral metabolites in vivo. However, measurement of concentrations of cerebral
      metabolites in patients with disturbances of cerebral development have not been
      successful. Our purpose was to measure the concentrations of cerebral metabolites
      in such patients. We carried out quantitative 1H-MRS in eight patients with
      cortical dysplasia, four with lissencephaly and three with heterotopic grey
      matter and six age-matched normal controls. Regions of interest for 1H-MRS were
      set over the affected cortex in the patients and the occipital cortex in
      controls. The calculated concentration of N-acetylaspartate ([NAA]) was
      significantly lower in the affected cortex in patients with cortical dysplasia (P
      < 0.05), lissencephaly (P < 0.01), and heterotopia (P < 0.05) than in controls,
      idnicating a decreased number and/or immaturity or dysfunction of neurones in the
      affected cortex. The concentration of choline ([Cho]) was significantly lower in
      patients with lissencephaly (P < 0.01) than in controls, indicating glial
      proliferation and/or membrane abnormality.

PMID- 11512592
TI  - Brain involvement in haemolytic-uraemic syndrome: MRI features of coagulative
      necrosis.
AB  - We describe radiological demonstration of brain involvement in haemolytic-uraemic
      syndrome (HUS) in two siblings with a very different clinical course. While the
      brother presented with a mild, reversible encephalopathy, his sister developed
      high-signal lesions in the cortex, putamen and caudate nucleus on T1-weighted
      images, seen as dense areas on CT. Biopsy revealed coagulative necrosis due to
      microthrombosis without haemorrhage, calcification or infection. These findings
      suggest a possible prognostic role for MRI in cases of encephalopathy due to HUS.

PMID- 11512593
TI  - Atypical focal non-neoplastic brain changes in neurofibromatosis type 1: mass
      effect and contrast enhancement.
AB  - Children and young adults with neurofibromatosis type 1 often have small high
      signal foci on T2-weighted images of the brain. We describe follow-up of two
      patients in whom one of the foci had atypical features, commonly regarded as
      signs of a neoplasm. In the first, one lesion showed temporary contrast
      enhancement and decreasing mass effect. The second developed an expanding lesion
      that increased minimally in size over 4.5 year's follow-up. The borderline
      between neoplastic and non-neoplastic lesions seems to be indistinct.

PMID- 11512594
TI  - Reperfusion demonstrated by apparent diffusion coefficient mapping after local
      intra-arterial thrombolysis for ischaemic stroke.
AB  - Diffusion-weighted MRI (DWI) is becoming important for diagnosis and
      investigation of acute cerebral ischaemia. It has been reported that apparent
      diffusion coefficient (ADC) maps could be an indicator of reperfusion. Our aim
      was to use echo-planar technology to investigate this phenomenon. We report 19
      patients treated by local intra-arterial thrombolysis for middle cerebral artery
      stroke within 6 h of the onset of symptoms, in whom we performed follow-up DWI.
      ADC were found to be higher in the patients with angiographically proven
      reperfusion.

PMID- 11512595
TI  - Bone disease in multiple myeloma: new markers, new treatments.

PMID- 11512596
TI  - Treatment of lupus nephritis: art or science?

PMID- 11512597
TI  - The Australian and New Zealand cardiac pacing and implantable cardioverter
      defibrillator survey: calendar year 1997.
AB  - BACKGROUND: A comprehensive pacemaker (PM) and implantable cardioverter
      defibrillator (ICD) survey was undertaken in Australia (Aus) and New Zealand (NZ)
      for calendar year 1997. RESULTS: Compared to the 1993 survey, significant
      increases in implantation numbers were recorded. For 1997, the total new PM
      implanted was 6,405 Aus (3,834 in 1993) and 823 NZ (530 in 1993). The number of
      new pacemaker implants per million population was 345 Aus (216 in 1993) and 228
      NZ (150 in 1993). Implantation centres increased between surveys from 49 to 92 in
      Aus and from seven to eight in NZ. There were smaller increases in pacemaker
      replacements between surveys with 735 in Aus (700 in 1993) and 126 in NZ (82 in
      1993). In both countries, pacemaker implants were performed predominantly by non
      surgeons. New recipients aged > 80 years were approximately 25% Aus and 30% NZ.
      The predominant indications were high degree atrio-ventricular block and sick
      sinus syndrome in both Aus and NZ. Dual chamber implants were 65% Aus and 55% NZ.
      The median hospital stay was about 2 days in Aus and 1 day in NZ. Pacing leads
      were overwhelmingly transvenous, bipolar and tined in both chambers. They were
      inserted via a cephalic vein cutdown in approximately 40% of cases in Aus and 49%
      in NZ. For ICD, the implants were 449 Aus (180 in 1993) and 31 NZ (10 in 1993)
      with new implants per million population being 24 Aus and eight NZ. A breakdown
      of data for the six Aus States is presented.

PMID- 11512598
TI  - Non-invasive markers of bone turnover and plasma cytokines differ in osteoporotic
      patients with multiple myeloma and monoclonal gammopathies of undetermined
      significance.
AB  - AIMS: To determine whether various markers of bone turnover and/or plasma
      cytokines differ in patients with multiple myeloma (MM) compared with patients
      with monoclonal gammopathies of undetermined significance (MGUS). METHODS: We
      studied 22 MM patients and 18 MGUS patients presenting over an 18-month period
      and compared their data with those from 20 age- and sex-matched patients
      presenting with primary osteoporosis. According to the Salmon and Durie
      classification, there were eight patients with stage I, nine with stage II and
      five with stage III disease. All patients had densitometric evidence of
      osteoporosis and were classified according to bone marrow evidence of plasma cell
      dyscrasia. Measured variables included markers of bone formation and bone
      resorption, and plasma cytokines. RESULTS: Patients with MM and MGUS did not
      differ with respect to their mean age, male : female sex ratio, height, weight,
      serum calcium, 25-hydroxyvitamin D and parathyroid hormone concentrations.
      Patients with MM had significantly lower concentrations of haemoglobin (109 vs
      135 g/L) and serum transforming growth factor (TGF)-beta (261 vs 348 pg/mL) than
      patients with MGUS, and higher concentrations of serum paraproteins (31.1 vs 7.4
      g/L), beta2-microglobulin (3.5 vs 2.2 g/L), % plasma cell numbers (35.3 vs 2.1%)
      and urinary deoxypyridinoline excretion rates (u-DPYD; 7.7 vs 5.9 nmol/mmol
      creatinine; P < 0.05 for all comparisons). In multivariate analysis, the serum
      paraprotein (beta coefficient = -0.067; 95% confidence intervals (CI), -0.019 to 
      0.005; P = 0.0012), u-DPYD excretion rates (beta coefficient = -0.012; 95% CI, 
      0.113 to -0.02; P= 0.0058) and serum TGF-beta concentrations (beta coefficient = 
      0.002; 95% CI, -0.0002 to -0.02; P= 0.02) were the most important variables
      differentiating between MM and MGUS, after excluding lytic bone lesions, % plasma
      cell numbers and haemoglobin concentrations. CONCLUSIONS: The well-established
      criteria for diagnosing MM include the presence of lytic bone lesions,
      plasmacytosis, haemoglobin and paraprotein concentrations. The u-DPYD excretion
      rate, a sensitive non-invasive marker of bone resorption, may help in
      differentiating between MM and MGUS, as well as serving as a marker of underlying
      bone disease activity in these patients.

PMID- 11512599
TI  - High-dose therapy and autologous transplantation for lymphoma: The Peter
      MacCallum Cancer Institute experience.
AB  - BACKGROUND: High-dose therapy (HDT) with autologous bone marrow or blood cell
      transplantation for the treatment of lymphoma commenced at Peter MacCallum Cancer
      Institute in 1986. AIM: To examine the patient characteristics and outcomes of
      patients with non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD) treated
      with HDT and autologous transplantation at our Institute in the first 10 years of
      the service (1986-95). METHODS: A retrospective analysis was performed examining
      patient characteristics, prior chemotherapy regimens, pretransplant disease
      status, HDT regimen, source of stem cells, time for haematopoietic recovery,
      complications of transplantation, response rates, overall survival (OS) and
      progression-free survival (PFS). RESULTS: Sixty-seven patients with NHL were
      treated with an estimated 5-year OS rate of 44% (95% confidence interval (CI) 32
      56%) and PFS rate of 34% (95% CI 21-44%). Factors independently predictive of an
      unfavourable PFS on multivariate analyses were presence of constitutional
      symptoms at transplant (P < 0.002) and chemotherapy-resistant disease at
      transplant (P = 0.02). Twenty-three patients with HD were treated with a 5-year
      predicted OS rate of 74% (95% CI 56-92%) and PFS rate of 57% (95% CI 36-77%).
      There was no difference in PFS for HD patients who relapsed either within 12
      months of completion of front-line therapy or after this time (P= 0.5). The
      transplant-related mortality for the entire cohort was 17%, with a progressive
      decrease over time. CONCLUSION: HDT with autologous transplantation achieves
      durable PFS and OS in patients with lymphoma. Improved patient selection, therapy
      modifications according to prognostic factors and ongoing improvements in
      supportive care should improve outcomes further.

PMID- 11512600
TI  - The mind of a failing heart: a systematic review of the association between
      congestive heart failure and cognitive functioning.
AB  - BACKGROUND: Congestive heart failure (CHF) is a frequent complication of most
      diseases of the heart. CHF is associated with impairment in several aspects of
      the quality of life of patients, including mood and cognitive performance. Early
      reports indicated that patients with CHF display deficits in memory and other
      intellectual abilities, although the clinical relevance of these findings remains
      unclear. AIM: We reviewed systematically the medical literature with the aim of
      clarifying the association between CHF and cognitive functioning. METHODS:
      Systematic review of Medline database for studies published between 1966 and June
      2000 using the following key words: congestive heart failure, cognition,
      cognitive disorders, memory, memory disorders, short-term memory, attention.
      RESULTS: Thirteen studies reported cognitive information on patients with CHF,
      but only five met inclusion criteria for systematic review. Three reports
      described attention (total number of subjects = 369 patients and 882 controls)
      and memory scores (total number of subjects = 247 patients and 748 controls), two
      studies reported measures of general cognitive functioning (total number of
      subjects = 203 patients and 704 controls) and one reported the rate of cognitive
      impairment (total number of subjects = 88 patients and 987 controls). Pooled
      analysis indicated that CHF is associated with a pattern of generalized cognitive
      impairment that includes memory and attention deficits. CONCLUSIONS: The results
      of the present review highlight the enormous paucity of systematic information
      about the association between CHF and cognitive functioning, with only five
      studies reporting data suitable for analysis. We expect that new case-control and
      cohort studies will be designed to confirm the presence of cognitive impairment
      in patients with CHF and trust that this information will improve the management
      of CHF patients and our understanding of the mechanisms associated with cognitive
      decline in later life.

PMID- 11512601
TI  - Towards a molecular approach to gastric cancer management.
AB  - Gastric cancer is a leading cause of cancer death worldwide. Most patients with
      gastric cancer present with locally advanced and incurable disease, and overall
      survival is poor. Considerable research efforts towards the epidemiology and
      pathogenesis of gastric cancer have not been translated into treatment success.
      We discuss current concepts of the pathogenesis of gastric cancer and how recent
      research advances, in particular global gene expression strategies, may improve
      this understanding, and suggest a framework wherein these approaches may be used.

PMID- 11512602
TI  - Papua and New Guinea medical experiences.

PMID- 11512603
TI  - When is an ANCA an anchor?

PMID- 11512604
TI  - Mycophenolate mofetil for treatment of refractory lupus nephritis.

PMID- 11512605
TI  - Rapid onset of pituitary apoplexy after goserelin implant for prostate cancer:
      need for heightened awareness.

PMID- 11512606
TI  - Recalcitrant leg ulcer as the initial manifestation of antiphospholipid syndrome
      in a 14-year-old boy.

PMID- 11512607
TI  - Excessive cola consumption as a cause of hypokalaemic myopathy.

PMID- 11512608
TI  - Spontaneous cholesterol embolization complicated by pulmonary fat embolism.

PMID- 11512609
TI  - The use of an MEG device as 3D digitizer and motion monitoring system.
AB  - An algorithm is described that localizes a set of simultaneously activated coils
      using MEG detectors. These coil positions are used for continuous or intermittent
      head position registration during long MEG sessions, to coregistrate MR and MEG
      data and to localize EEG electrodes attached to the scalp, when EEG and MEG are
      recorded simultaneously. The algorithm is based on a mathematical model in which
      the coils are described as stationary magnetic dipoles with known source time
      functions. This knowledge makes it possible to detect and remove bad channels
      automatically. It is also assumed that the source time functions are orthogonal.
      Therefore, the localization problem splits into independent localization
      problems. for each coil. The method is validated in a phantom experiment, where
      the relative coil positions were known. From this experiment it is found that the
      average error is 0.25 cm. An error of 0.23 cm was found in an experiment where 64
      electrode positions were measured four times independently. Examples of the
      applications of the method are presented. Our method eliminates the use of an
      external 3D digitizer and maps the MEG directly onto other modalities. This is
      not only a practical advantage, but it also reduces the gross registration error.
      Furthermore, head motions can be monitored and MEG data can be corrected for
      these motions.

PMID- 11512610
TI  - In vivo cerebrovascular measurement combining diffuse near-infrared absorption
      and correlation spectroscopies.
AB  - We combine two near-infrared diffuse optical techniques to study variations of
      blood flow, haemoglobin concentration, and blood oxygen saturation in the
      functioning rat brain. Diffuse correlation spectroscopy (or flowmetry) monitors
      changes in the cerebral blood flow, without the use of the principles of tracer
      clearance, by measuring the optical phase-shifts caused by moving blood cells.
      Near-infrared absorption spectroscopy concurrently measures tissue absorption at
      two wavelengths to determine haemoglobin concentration and blood oxygen
      saturation in this same tissue volume. This optical probe is non-invasive and was
      employed through the intact skull. The utility of the technique is demonstrated
      in vivo by measuring the temporal changes in the regional vascular dynamics of
      rat brain during hypercapnia. Temporal and spatial variations of cerebral blood
      flow, haemoglobin concentration and blood oxygen saturation during hypercapnia
      are compared with other measurements in the literature, and a quantitative
      analysis demonstrating the self-consistency of our combined observations of
      vascular response is presented.

PMID- 11512611
TI  - Photon path distribution and optical responses of turbid media: theoretical
      analysis based on the microscopic Beer-Lambert law.
AB  - A concise theoretical treatment has been developed to describe the optical
      responses of a highly scattering inhomogeneous medium using functions of the
      photon path distribution (PPD). The treatment is based on the microscopic Beer
      Lambert law and has been found to yield a complete set of optical responses by
      time- and frequency-domain measurements. The PPD is defined for possible photons
      having a total zigzag pathlength of l between the points of light input and
      detection. Such a distribution is independent of the absorption properties of the
      medium and can be uniquely determined for the medium under quantification.
      Therefore, the PPD can be calculated with an imaginary reference medium having
      the same optical properties as the medium under quantification except for the
      absence of absorption. One of the advantages of this method is that the optical
      responses, the total attenuation, the mean pathlength, etc are expressed by
      functions of the PPD and the absorption distribution.

PMID- 11512612
TI  - An automated technique for SPECT marker-based image registration in radionuclide
      therapy.
AB  - An automated technique for marker-based image registration in radionuclide
      therapy is described. This technique is based on localization of the centroids of
      external markers and on establishing correspondence between the individual
      markers of the two studies to be registered. Localization of the centroids of
      markers relies on segmenting the markers using iterative thresholding.
      Thresholding is locally adaptive in order to account for study-dependent
      conditions (e.g. crossover between adjacent markers and markers with varying
      radioactive concentrations). Following marker segmentation, the centroids of the
      markers are computed based on an intensity-weighted method. Finally, prior to the
      least-squares fit registration, the markers of the two sets are matched to
      achieve one-to-one correspondence. The technique was applied to both simulated
      and patient studies resulting in mean residual three-dimensional registration
      errors (+/- 1SD) of 1.7 +/- 0.1 mm and 3.5 +/- 0.3 mm respectively. The technique
      was compared with a semi-automated approach and no significant difference was
      found between the mean residual three-dimensional registration errors (t = 0.281.
      p = 0.8). This automated marker-based image registration technique provides
      robust and accurate registration. Although it was developed as part of a
      programme to generate three-dimensional dose distributions for radionuclide
      therapy, it could be useful for other clinical applications.

PMID- 11512613
TI  - Analysis of low-angle x-ray scattering peaks from lyophilized biological samples.
AB  - Low-angle x-ray scattering (LAXS) from lyophilized blood and its constituents is
      characterized by the presence of two peaks in the forward direction of
      scattering. These peaks are found to be sensitive to the variations in the
      molecular structure of a given sample. The present work aims to explore the
      nature of LAXS from a variety of lyophilized biological samples. It also aims to
      investigate the possibility that a certain biological macromolecule is
      responsible of the production of LAXS peaks. This is carried out through
      measurements of LAXS from complex biological samples and their basic
      constituents. Among the measured samples are haemoglobin (Hb), globin, haem,
      packed red blood cells, bovine albumin, egg albumin, milk, casein, glutamine,
      alanine, fat, muscle and DNA. A table containing some characteristic parameters
      of the LAXS profiles of these samples is also presented. Analysis of measured
      profiles shows that all lyophilized samples produce at least one relatively broad
      peak at a scattering angle around 10.35 degrees. The full width at half maximum
      (FWHM) of this peak varies considerably among the measured samples. Except for
      milk and casein. one additional peak at a scattering angle around 4.65 degrees is
      observed only in the LAXS profiles of proteins or protein-rich samples. This fact
      strongly suggests protein to be the biological macromolecule from which this
      characteristic peak originates. The same idea is further strengthened through
      discussion of some previous observations.

PMID- 11512614
TI  - Air kerma calibration factors and chamber correction values for PTW soft x-ray,
      NACP and Roos ionization chambers at very low x-ray energies.
AB  - This paper evaluates the characteristics of ionization chambers for the
      measurement of absorbed dose to water using very low-energy x-rays. The values of
      the chamber correction factor, k(ch), used in the IPEMB 1996 code of practice for
      the UK secondary standard ionization chambers (PTW type M23342 and PTW type
      M23344), the Roos (PTW type 34001) and NACP electron chambers are derived. The
      responses in air of the small and large soft x-ray chambers (PTW type M23342 and
      PTW type M23344) and the NACP and Roos electron ionization chambers were
      compared. Besides the soft x-ray chambers, the NACP and Roos chambers can be used
      for very low-energy x-ray dosimetry provided that they are used in the restricted
      energy range for which their response does not change by more than 5%. The
      chamber correction factor was found by comparing the absorbed dose to water
      determined using the dosimetry protocol recommended for low-energy x-rays with
      that for very low-energy x-rays. The overlap energy range was extended using data
      from Grosswendt and Knight. Chamber correction factors given in this paper are
      chamber dependent, varying from 1.037 to 1.066 for a PTW type M23344 chamber,
      which is very different from a value of unity given in the IPEMB code. However,
      the values of k(ch) determined in this paper agree with those given in the DIN
      standard within experimental uncertainty. The authors recommend that the very low
      energy section of the IPEMB code is amended to include the most up-to-date values
      of k(ch).

PMID- 11512615
TI  - Comparison of dosimetric standards of Canada and France for photons at 60Co and
      higher energies.
AB  - We report the results of a comparison of the dosimetric standards of Canada and
      France for photon beams at 60Co and a few higher energies. The present primary
      standard of absorbed dose to water for NRC, Canada is based on measurements made
      with a sealed water calorimeter. The corresponding standard of the LNHB, France
      is based on measurements made with a graphite calorimeter at 60Co energy and
      transferred to absorbed dose to water for 60Co and higher-energy photon beams
      using both ion chambers and Fricke dosemeters as transfer instruments. To make
      this comparison, we used three graphite-walled NE2571 Farmer chambers. The
      absorbed dose to water determined by the LNHB was greater than that determined by
      NRC by 0.20% at 60Co energy. This difference is not significant given the
      uncertainties on the standards. In order to do the comparison for higher-energy
      photons, we interpolated the NRC data set at the beam qualities used at the LNHB.
      When %dd(10)x is used as the method of specifying beam quality, the determination
      of absorbed dose to water by the LNHB is about 0.2% greater than that determined
      by NRC and consistent with the results at 60Co. However, when using TPR20,10 as
      the beam quality specifier, the LNHB determination is greater than the NRC's
      determination by 0.8% and 1.2% at 12 and 20 MV respectively. This discrepancy,
      which systematically increases with increasing energy, eventually exceeds the
      uncertainties in the ratio of the standards, estimated to be 0.7%. This
      underscores the importance of selecting the method of specifying beam quality,
      either %dd(10)x or TPR20,10, at least for the 'soft' beams used by NRC in this
      comparison. In the case of the air kerma standards, which were also compared at
      60Co energy, the LNHB determination was greater than NRC's by 0.14%, which is not
      significant given the uncertainties on the standards.

PMID- 11512616
TI  - Wide dynamic dose range of VIPAR polymer gel dosimetry.
AB  - In this work the extent of the linear dose response and the dynamic dose range of
      N-vinylpyrrolidone-argon based (VIPAR) polymer gels were investigated. VIPAR gels
      were irradiated using a 6 MV linear accelerator up to 60 Gy and a Nucletron
      microSelectron 192Ir HDR brachytherapy source to much higher doses to cover a
      dose range of two orders of magnitude. They were then MR scanned at 1.5 T to
      obtain T2-maps. VIPAR gel measurements obtained from the two irradiation regimes
      were calibrated against ion chamber measurements and dose calculations derived
      using the AAPM TG-43 protocol respectively. A satisfying agreement between the
      calibration results derived using the 6 MV x-rays and the 192Ir source was found
      for doses up to 60 Gy, implying that the response of the VIPAR gels is
      independent of photon energy and dose rate. A linear R2 dose response up to
      approximately 40 Gy and a dynamic dose range up to at least approximately 250 Gy
      were observed. VIPAR gel dose measurements derived using the monoexponentially
      fitted brachytherapy calibration data were found to be quite accurate.

PMID- 11512617
TI  - A multiobjective gradient-based dose optimization algorithm for external beam
      conformal radiotherapy.
AB  - A multiobjective gradient-based algorithm has been developed for the purpose of
      dose distribution optimization in external beam conformal radiotherapy. This
      algorithm is based on the concept of gathering the values of all objectives into
      a single value. The weighting factors of the composite objective values are
      varied in different steps, allowing the reconstruction of the trade-off surfaces
      (three or more objectives) or curves (two objectives) which define the boundary
      between the feasible and non-feasible domain regions. The analysis of these
      curves allows the decision-maker to select the solution that best fits the
      clinical goals. In contrast to all the other algorithms, our method provides not
      a single solution but a sample of solutions representing all possible clinical
      importance factors (weights) for the objectives used. The application of this
      algorithm to two test cases shows that a correct selection for the importance
      factors to multiply the individual objectives in the global objective value is
      not trivial and that the location and shape of the boundary region between the
      feasible and non-feasible solution regions are case dependent. Provided that the
      individual objective functions are analytically differentiable and that the
      number of objectives is the range of two to three, the computation times are
      acceptable for clinical use. Furthermore, the optimization for a unique
      combination of importance factors within the aggregate objective function is
      performed in less than 1 min.

PMID- 11512618
TI  - Monte Carlo based treatment planning for modulated electron beam radiation
      therapy.
AB  - A Monte Carlo based treatment planning system for modulated electron radiation
      therapy (MERT) is presented. This new variation of intensity modulated radiation
      therapy (IMRT) utilizes an electron multileaf collimator (eMLC) to deliver non
      uniform intensity maps at several electron energies. In this way, conformal dose
      distributions are delivered to irregular targets located a few centimetres below
      the surface while sparing deeper-lying normal anatomy. Planning for MERT begins
      with Monte Carlo generation of electron beamlets. Electrons are transported with
      proper in-air scattering and the dose is tallied in the phantom for each beamlet.
      An optimized beamlet plan may be calculated using inverse-planning methods. Step
      and-shoot leaf sequences are generated for the intensity maps and dose
      distributions recalculated using Monte Carlo simulations. Here, scatter and
      leakage from the leaves are properly accounted for by transporting electrons
      through the eMLC geometry. The weights for the segments of the plan are re
      optimized with the leaf positions fixed and bremsstrahlung leakage and electron
      scatter doses included. This optimization gives the final optimized plan. It is
      shown that a significant portion of the calculation time is spent transporting
      particles in the leaves. However, this is necessary since optimizing segment
      weights based on a model in which leaf transport is ignored results in an
      improperly optimized plan with overdosing of target and critical structures. A
      method of rapidly calculating the bremsstrahlung contribution is presented and
      shown to be an efficient solution to this problem. A homogeneous model target and
      a 2D breast plan are presented. The potential use of this tool in clinical
      planning is discussed.

PMID- 11512619
TI  - Assessment of the linear reference air kerma rate of 192Ir wires.
AB  - In this study, a procedure to test the linear reference air kerma rate of 192Ir
      wires using a well-type chamber is described. The method is based on a special
      lead insert with a 1 cm acrylic aperture that provides a differential response of
      the well chamber. The wire is considered divided into 1 cm parts. Using an
      external positioning system it is possible to place every part of the wire at the
      aperture position in the lead insert allowing measurement of each 1 cm making up
      the length of the wire. By means of a set of equations that take into account the
      contribution of all parts of the wire, in all possible positions, the relative
      linear reference air kerma rate is obtained. The estimated uncertainties of this
      procedure are about 2 to 3%. So, a well chamber and the specific inserts allow
      the measurements of total and linear reference air kerma rate for 192Ir wires.

PMID- 11512620
TI  - Precise measurement of cerebral blood flow in newborn piglets from the bolus
      passage of indocyanine green.
AB  - Indocyanine green (ICG) is a near-infrared dye that has the potential to be used
      as a tracer for the minimally invasive measurement of cerebral blood flow (CBF).
      In order to examine the technique, the arterial and cerebral concentrations of
      ICG were measured in newborn piglets during the bolus passage of ICG at
      normocapnia and two levels of mild hypercapnia. The results were analysed by
      applying the Fick principle in both integral and differential forms using a
      linear regression technique to improve the precision of calculated values of CBF.
      It was found that the integral method, which has been used previously, is
      particularly sensitive to errors in the time registration between the arterial
      and tissue signals whereas the differential method is less so. In addition, the
      differential method allows the venous outflow to be calculated which gives
      further information on the state of the capillary bed. CBF was 39.7 +/- 4.6 ml
      100 g(-1) min(-1) at an arterial carbon dioxide tension (PaCO2) of 33.0+/-2.2
      mmHg and increased to 53.7+/-9.1 and 75.4+/-15.2 ml 100 g(-1) min(-1) at a PaCO2
      of 42.1 +/- 2.6 and 54.2 +/- 3.1 mmHg respectively (mean +/- SD, n = 7). There
      was no significant change in cerebral metabolic rate for oxygen, validating the
      value of blood flow to an arbitrary scaling factor. When the inspired CO2
      fraction was returned to zero, calculated CBF returned to baseline with a
      variation of 7% of the mean, indicating that this technique is highly precise.

PMID- 11512621
TI  - In vivo optical characterization of human tissues from 610 to 1010 nm by time
      resolved reflectance spectroscopy.
AB  - A fully automated system for time-resolved reflectance spectroscopy based on
      tunable mode-locked laser sources and on time-correlated single-photon counting
      for the detection of time-resolved reflectance data was applied to the evaluation
      of the optical properties of biological tissues (arm, abdomen and forehead) in
      vivo from 610 to 1010 nm. The scattering decreases progressively with increasing
      wavelength, while the absorption line shapes show the typical spectral features
      of the principal tissue components (haemoglobin, water and lipid), with different
      weights depending on the tissue type. The best fit of the absorption spectra
      measured in vivo with the spectra of the pure constituents yielded information on
      the percentage composition of the different tissues. The interpretation of
      transport scattering spectra with Mie theory provided information on tissue
      structure.

PMID- 11512622
TI  - Resolution recovery for list-mode reconstruction in SPECT.
AB  - The purpose of the study was to evaluate the resolution recovery in the list-mode
      iterative reconstruction algorithm (LMIRA) for SPECT. In this study we compare
      the performance of the proposed method with other iterative resolution recovery
      methods for different noise levels. We developed an iterative reconstruction
      method which uses list-mode data instead of binned data. The new algorithm makes
      use of a more accurate model of the collimator structure. We compared the SPECT
      list-mode reconstruction with MLEM, OSEM and RBI, all including resolution
      recovery. For the evaluation we used Gaussian shaped sources with different FWHM
      at three different locations and three noise levels. For these distributions we
      calculated the reconstructed images for a different number of iterations. The
      absolute error for the reconstructed images was used to evaluate the performance.
      The performance of all four methods is comparable for the sources located in the
      centre of the field of view. For the sources located out of the centre, the error
      of the list-mode method is significantly lower than that of the other methods.
      Splitting the system model into a separate object-dependent and detector
      dependent module gives us a flexible reconstruction method. With this we can very
      easily adapt the resolution recovery to different collimator types.

PMID- 11512623
TI  - A study of equivalent source techniques for high-resolution EEG imaging.
AB  - High-resolution EEG imaging has been an important topic in recent EEG research,
      and much work has been done on the two equivalent source imaging techniques: the
      equivalent distributed dipole-layer source imaging technique (EST) and the
      equivalent multipole source imaging technique (SAT). In this paper we first
      develop a forward density formula for a spherical equivalent distributed dipole
      layer of an arbitrary dipole in a three-concentric-sphere head model. It is
      clarified using the derived forward formula that the equivalent dipole-layer
      source and equivalent multipole source are interrelated in theory. Finally,
      simulation comparisons are conducted, the results of which suggest that EST has a
      higher spatial resolution than SAT when both of them are implemented by a
      truncated singular value decomposition algorithm. This is due to the different
      singularities of the inversion equations involved in the two techniques. An
      empirical VEP data study also shows that EST is better than SAT in providing
      higher spatial resolution EEG imaging.

PMID- 11512624
TI  - Visible dye light absorption properties of processed radiographic film.
AB  - The visible absorption spectra of Kodak X-Omat V film, which had been exposed to
      various doses of radiation, have been investigated to analyse the dosimetry
      characteristics of the film with various densitometers. Common densitometers can
      use fluorescent light (broad band visible), helium-neon (632 nm) or other spectra
      of specific bandwidth. The visible absorption spectra show a slight peak in
      absorption at approximately 580 nm and another at 630 nm caused by the base
      material of the film. The optical density of the film is shown to increase almost
      equally at all wavelengths within the visible region with increases in applied
      dose. By evaluating the results for the broad band spectra and specific
      wavelength optical density it is shown that a relatively uniform response is
      expected for all densitometers that work within the visible region as well as in
      selected infrared wavelengths. Thus similar optical density to dose response
      curves for X-Omat V radiographic film should be produced for all types of
      densitometers, no matter what type of light source is used for illumination. Thus
      it is most efficient to have a densitometer with a light source suitable for
      radiochromic film, which can also be used with radiographic film.

PMID- 11512625
TI  - An iterative algorithm for reconstructing incident beam distributions from
      transmission measurements using electronic portal imaging.
AB  - The problem of reconstructing incident radiotherapy beam profiles from electronic
      portal images recorded behind a phantom is addressed. To this end an iterative
      algorithm is presented, which is able to extract the input beam profile from a
      portal image by compensating for the attenuation of the beam and subtracting the
      amount of scatter emitted by the phantom. The algorithm requires only a thickness
      map of the phantom. Scatter is estimated using a superposition method based on
      precalculated Monte Carlo scatter kernels. The method is tested for a homogeneous
      water-equivalent slab phantom for simple rectangular and complex multileaf
      collimated fields. It is shown that the method produces a stable result within
      four iterations yielding an accuracy for the incident beam distribution of better
      than 3%.

PMID- 11512626
TI  - A 3D MRI sequence for computer assisted surgery of the lumbar spine.
AB  - The aim of this research was to develop a magnetic resonance (MR) sequence
      capable of producing images suitable for use with computer assisted surgery (CAS)
      of the lumbar spine. These images needed good tissue contrast between bone and
      soft tissue to allow for image segmentation and generation of a 3D-surface model
      of the bone for surface registration. A 3D double echo fast gradient echo
      sequence was designed. Images were filtered for noise and non-uniformity and
      combined into a single data set. Registration experiments were carried out to
      directly compare segmentation of MR and computed tomography (CT) images using a
      physical model of a spine. These experiments showed the MR data produced adequate
      surface registration in 90% of the experiments compared to 100% with CT data. The
      MR images acquired using the sequence and processing described in this article
      are suitable to be used with CAS of the spine.

PMID- 11512627
TI  - Nitrate exposure and the endogenous formation of carcinogenic nitrosamines in
      humans.

PMID- 11512628
TI  - Direct exposure to animal enteric pathogens.
AB  - Humans have very close interactions with working, food-producing, and companion
      animals. According to the American Veterinary Medical Association, there are more
      than one hundred million cat and dog pets in the United States. Furthermore, non
      traditional pets like reptiles and exotic birds are not unusual companion animals
      in households. In addition to sharing with animals our living and/or working
      space and time, we also share, unfortunately, many disease causing
      microorganisms. In the past few years, we have become aware that several enteric
      pathogens that were thought to be mostly restricted to animals are a major cause
      of human disease. Examples of such pathogens include the protozoan parasite
      Cryptosporidium parvum and bacteria such as Campylobacter spp. This review will
      examine the characteristics of zoonotic enteric pathogens including bacterial
      (Helicobacter spp., Campylobacter spp., Salmonella spp., and verotoxin-producing
      Escherichia coli); parasitic (Toxoplasma gondii, Giardia spp., Cryptosporidium
      spp.); and viral (rotavirus, norwalk-like virus, hepatitis E virus), and the
      status of our knowledge with regard to the impact of such pathogens on human
      health.

PMID- 11512629
TI  - Air pollution and health effects in northern Nevada.
AB  - The issue of adverse health effects of ambient air pollution has been extensively
      studied and reported worldwide over the past two decades. The urban area of Reno
      and Sparks in northern Nevada is one of two major urban centers in Nevada; the
      other is Las Vegas. The northern area, which has undergone a rapid population
      growth in the last decade, has special geographic characteristics and air
      pollution patterns. We conducted environmental epidemiological studies spanning
      the 1990s. This report summarizes the evidence and discusses the findings in
      relation to other studies. Ambient air pollution levels, even when below federal
      standards, have a marked potential to impact human health adversely. Air
      pollution was associated with (1) emergency room visits for asthma; (2)
      hospitalization for chronic obstructive pulmonary disease; (3) hospitalization
      for cardio-vascular disease; (4) elementary school absenteeism; and (5) low birth
      weight, preterm birth, and other adverse birth outcomes.

PMID- 11512630
TI  - European aspects of standard setting in occupational hygiene and medicine.
AB  - Occupational standards concerning the allowable concentrations of chemical
      compounds in the ambient air of workplaces have been established in several
      countries at national levels. With the integration of the European Union, a need
      exists for establishing harmonized Occupational Exposure Limits. For analytical
      developments, it is apparent that methods for speciation or fractionation of
      carcinogenic metal compounds will be of increasing practical importance for
      standard setting. Criteria of applicability under field conditions, cost
      effectiveness, and robustness are practical driving forces for new developments.
      When the European Union issued a list of 62 chemical substances with Occupational
      Exposure Limits in 2000, 25 substances received a 'skin' notation. The latter
      indicates that toxicologically significant amounts may be taken up via the skin.
      Similar notations exist on national levels. For such substances, monitoring
      concentrations in ambient air will not be sufficient; biological monitoring
      strategies will gain further importance in the medical surveillance of workers
      who are exposed to such compounds. Proceedings in establishing legal frameworks
      for a biological monitoring of chemical exposures within Europe are paralleled by
      scientific advances in this field. A new aspect is the possibility of a
      differential adduct monitoring, using blood proteins of different half-life or
      lifespan. This technique allows differentiation between long-term mean exposure
      to reactive chemicals and short-term episodes, for example, by accidental
      overexposure. For further analytical developments, the following issues have been
      addressed as being particularly important: New dose monitoring strategies,
      sensitive and reliable methods for detection of DNA adducts, cytogenetic
      parameters in biological monitoring, methods to monitor exposure to sensitizing
      chemicals, and parameters for individual susceptibilities to chemical toxicants.

PMID- 11512631
TI  - Occupational airway diseases.
AB  - In this review we describe characteristics of occupational airway diseases, as
      well as physical and chemical characteristics of agents inducing airway disease.
      Occupational airway diseases include industrial bronchitis, reactive airway
      dysfunction syndrome, bronchiolitis obliterans, and occupational asthma. High-
      and low-molecular weight substances associated with occupational airway disease
      are listed. The importance of host factors is stressed. Diagnostic approaches,
      particularly indicators for specific challenge testing with occupational
      materials, are described. Preventive and control measures are presented.

PMID- 11512632
TI  - Health effects of indoor molds.
AB  - Molds grow readily indoors in the presence of dampness. Their visibility enables
      their effects to be investigated by means of questionnaire surveys, although
      these are subject to imprecision and potential bias. Exposure to airborne mold
      particles can be measured in various ways that also have disadvantages and
      limitations. Many surveys have been conducted on the health effects of molds;
      most have examined the association between molds and symptoms, although some
      studies have used lung function tests and other objective health indices. Most
      surveys suggest that indoor mold growth is associated with ill health,
      particularly of the respiratory tract. Knowing how important mold exposure really
      is in health terms is difficult, owing to the tendency for mold growth to be
      associated with other factors that are prejudicial to health.

PMID- 11512633
TI  - Cell kinetics in a model of artificial skin. An immunohistochemical and flow
      cytometric analysis.
AB  - Bioengineered organs raised in vitro are candidate substitutes for natural organs
      in biological, pharmacological and clinical applications. We have studied cell
      kinetics in a human skin equivalent (HSE) using a combined immunohistochemical
      and flow cytometric approach. Morphological analysis has shown that, relative to
      unstimulated natural skin, cell proliferation mainly occurs in the basal layer of
      the epidermal equivalent. Immunohistochemical and flow cytometric measurements of
      the growth fraction suggested a cell turnover comparable to that of natural skin.
      Immunohistochemical labelling indices matched well with flow cytometric data.
      These observations are consistent with morphological and histochemical data
      demonstrating normal cell differentiation and tissue architecture in HSE and
      suggest that such HSE may be a usefull substitute for human skin.

PMID- 11512634
TI  - Hyaluronate and CD44 expression patterns in the human placenta throughout
      pregnancy.
AB  - Hyaluronan (HA) and CD44 are involved in several processes such as cell migration
      and differentiation. In the present study, we examined the expression and
      distribution of both hyaluronan and its cell surface receptor (CD44) in the human
      placenta, which is a rapidly growing and differentiating organ that plays a
      fundamental role in fetal life. Hyaluronan was detected by a specific
      biotinylated binding probe, termed b-PG. In the first half of gestation, HA was
      strongly expressed in the stroma of the mesenchymal villi which have been
      previously identified as responsible for the growth and differentation of the
      villous trees. The other villous types showed an intense staining only in the
      fetal vessel walls and in the connective tissue closely underlying the
      trophoblastic cover. In addition, hyaluronan positive staining was also apparent
      in a restricted rim of villous stroma directly apposed to extravillous
      cytotrophoblastic cell islands and cell columns. In full term placentas, all
      villi expressed HA in their stromal tissue with a more homogenous staining than
      in the first half of gestation. In contrast to hyaluronan, in the first trimester
      CD44 was restricted to some of the Hofbauer cells which may be able to
      internalize hyaluronan, thus playing a significant role in its removal in early
      pregnancy. CD44 was primarily expressed starting from the 16th week of gestation.
      At the end of pregnancy it was expressed in the various villous types, especially
      in stem villi. Moreover, the plasma membrane of some extravillous
      cytotrophoblastic cells in the basal plate and the large majority of the decidual
      cells showed a positive immunostaining for this receptor. Taken together, these
      data suggest that HA is strongly involved in early villous morphogenesis, whereas
      CD44 seem to be play an important role in tissue remodelling later in gestation.

PMID- 11512635
TI  - Lactate dehydrogenase activity of rat epididymis and spermatozoa: effect of
      constant light.
AB  - During its passage through the epididymis, the gamete undergoes a process of
      "maturation" leading to the acquisition of its fertilizing ability. The
      epididymis displays regional variations in the morphology and metabolic
      properties of its epithelium which are relevant for the progressive development
      of mature sperm characteristics. The epididymis has spontaneous peristaltic
      contractions and receives sympathetic innervation that is modulated by melatonin,
      a hormone synthesized and released by the pineal gland. Constant lighting
      disrupts melatonin synthesis and secretion. We have studied the effect of
      constant light on lactate dehydrogenase (LDH; EC 1.1.1.27) and its isozyme C4
      activities and protein content in whole epididymis, epididymal tissue and in
      spermatozoa from caput and cauda segments. Animals were exposed from birth to an
      illumination schedule of 14 h light:10 h dark (group L:D). At 60 days of age one
      group of animals was submitted to constant light over 50 days (group L:L). In
      order to test the fertilizing ability, the rats of each group were mated with
      soliciting estrous females. The percentage of pregnancies in females mated with
      males maintained in L:L was remarkably lower than those in females mated with
      males maintained in the L:D photoperiod (44% and 88% respectively). Constant
      light increased protein concentration and LDH activity in caput as well as in
      cauda of total epididymis. On the contrary, in epididymal tissue, the protein
      content decreased in both epididymal sections compared with controls. When
      enzymatic activity was expressed in Units per spermatozoa, constant light induced
      a significant reduction of total LDH and LDHC4 in caput and cauda spermatozoa
      while LDH activity of epididymal tissue was not affected. In spite of the
      decrease in LDH per sperm cell when rats were exposed to constant light, in total
      epididymis (epididymis tissue plus sperm cells content) and in spermatozoa,
      values of enzyme activities expressed per weight unit were higher than those of
      controls. This is explained by the increase in the amount of stored spermatozoa,
      both in caput and cauda, produced by exposure of animals to constant light. Our
      results confirm that in rats, chronic exposure to constant light promotes a
      reduction of fertilizing ability and indicates that continuous lighting reduces
      the total LDH and LDHC4 activities, possibly due to moderate aging of spermatozoa
      within the duct by lengthening of the sperm transit through the epididymis.

PMID- 11512636
TI  - Epithelial-mesenchymal interactions and lung branching morphogenesis. Role of
      polyamines and transforming growth factor beta1.
AB  - Lung branching morphogenesis is a result of epithelial-mesenchymal interactions,
      which are in turn dependent on extracellular matrix composition and cytokine
      regulation. Polyamines have recently been demonstrated as able to modify chick
      embryo skin differentiation. In this work we have examined the effects of
      putrescine and spermidine during chick embryo lung morphogenesis in organotypic
      cultures by morphological, histochemical and biochemical examination. To verify
      the role of polyamines, we used specific inhibitors, such as bis
      cyclohexylammonium sulphate and alfa-difluoromethylornithine, and transforming
      growth factor beta1, an ornithine decarboxylase and polyamine stimulator. Our
      data show that lung morphogenesis is significantly altered following the induced
      mesenchymal glycosaminoglycan changes. The increase of mesenchymal
      glycosaminoglycans is correlated with a stimulation of lung development in the
      presence of polyamines, and with its inhibition when transforming growth factor
      beta1 is added to the culture medium. The morphometric data show a uniform
      increase of both the mesenchyme and epithelial branching with spermidine and
      putrescine stimulus, whereas the mesenchymal substance alone is significantly
      increased in apical-median lung sections with transforming growth factor beta1
      and transforming growth factor beta1 + spermidine lung cultures. Transforming
      growth factor beta1 and transforming growth factor beta1 + spermidine confirm the
      blocking of epithelial branching formations and fibroblast activation, and show
      that polyamines are unable to prevent the blocking of epithelial cells due to the
      inhibitory effect of transforming growth factor beta1.

PMID- 11512637
TI  - The hypothalamic magnocellular neurosecretory system in developing rats.
AB  - Studies concerning the development of the magnocellular system are scarce and
      discordant in literature. We carried out an immunohistochemical study on
      supraotic and paraventricular hypothalamic nuclei using antivasopressin and
      antioxytocin antibodies in developing rats between the 15th day of intrauterine
      life and the 6th day of postnatal life. In addition, we performed RT-PCR
      experiments to establish the stage at which these hormones appear and
      neurosecretory activity commences. The results showed that supraoptic and
      paraventricular nuclei appear, respectively, on the 16th and the 18th day of
      intrauterine life and both immediately synthetize vasopressin neurohormone. By
      contrast, synthesis of oxytocin takes place from the 2nd day after birth.
      Probably, these nuclei synthetize oxytocin in conjunction with the decline of
      placental maternal oxytocin.

PMID- 11512638
TI  - Early events of secretory granule formation in the rat parotid acinar cell under
      the influence of isoproterenol. An ultrastructural and lectin cytochemical study.
AB  - The events involved in the maturation process of acinar secretory granules of rat
      parotid gland were investigated ultrastructurally and cytochemically by using a
      battery of four lectins [Triticum vulgaris agglutinin (WGA), Ulex europaeus
      agglutinin I (UEA-I), Glycine max agglutinin (SBA), Arachys hypogaea agglutinin
      (PNA)]. In order to facilitate the study, parotid glands were chronically
      stimulated with isoproterenol to induce secretion. Specimens were embedded in the
      Lowicryl K4M resin. The trans-Golgi network (TGN) derived secretory granules,
      which we refer to as immature secretory granules, were found to be intermediate
      structures in the biogenesis process of the secretory granules in the rat parotid
      acinar cell. These early structures do not seem to be the immediate precursor of
      the mature secretory granules: in fact, a subsequent interaction process between
      these early immature granule forms and TGN elements seems to occur, leading,
      finally, to the mature granules. These findings could explain the origin of the
      polymorphic subpopulations of the secretory granules in the normal acinar cells
      of the rat parotid gland. The lectin staining patterns were characteristic of
      each lectin. Immature and mature secretory granules were labelled with WGA, SBA,
      PNA, and lightly with UEA-I. Cis and intermediate cisternae of the Golgi
      apparatus were labelled with WGA, and trans cisternae with WGA and SBA.

PMID- 11512639
TI  - Comparative histochemical study of Bowen's disease and actinic keratosis:
      preserved normal basal cells in Bowen's disease.
AB  - The degree of DNA-instability as revealed by immunohistochemical staining with
      anti-cytidine antibody after acid hydrolysis (DNA-instability test) has been
      recently used as a marker of malignancy. This technique was applied to examine 17
      skin tissue samples of Bowen's disease, 47 of actinic keratosis, 15 of squamous
      cell carcinoma, 5 of seborrheic keratosis, and 10 of normal skin. All benign
      neoplastic cells of seborrheic keratosis and normal epidermal cells were
      negative. On the other hand, all cancer cells were positive with the DNA
      instability test, indicating their malignancy, but all basal cells in Bowen's
      disease were completely negative. Compatible with this result, the basal cells in
      Bowen's disease were characteristically normal as evident in other histochemical
      examinations. Thus, they were negative with p53 immunohistochemistry, with normal
      signals of chromosome 17 in situ hybridisation and argyrophilic nucleolar
      organiser region, and showed slightly enhanced proliferative activity as revealed
      by proliferating cell nuclear antigen immunohistochemistry. Immunohistochemical
      staining with 34 beta E12 (monoclonal antibody against cytokeratins 1, 5, 10, and
      14), which stains all normal epidermal keratinocytes including basal cells,
      showed that only the basal cells of Bowen's disease stained strongly and
      homogeneously, while all cancer cells in the upper layers of Bowen's disease and
      all layers of actinic keratosis were only sporadically or weakly stained.
      Staining with 34 beta B4 (monoclonal antibody against cytokeratin 1), which
      recognises the whole epidermis except for the basal layer in the normal
      epidermis, showed that the basal cells in the Bowen's disease were completely
      negative, and lower layer cells in the actinic keratosis and upper layer cells in
      Bowen's disease were only sporadically stained positive, although the superficial
      layer cells in actinic keratosis stained strongly and homogeneously. Our findings
      clearly indicate that the basal cells in Bowen's disease are normal. In support
      of this conclusion, the same cells showed normal morphology on electron
      microscopy with preserved basement membrane, although the latter was often
      damaged in actinic keratosis.

PMID- 11512640
TI  - Proliferative activity and motoneurone recruitment persist at the spinal cord
      central canal during larval and some postlarval stages in the rainbow trout
      (Oncorhynchus mykiss).
AB  - We previously found a linear relationship between the cross sectional myotomal
      area and the motoneurone number in the growing trout during postlarval stages.
      These neurones increased in number until a fish length of 150 mm, which prompted
      us to examine how motor neurones are recruited afterwards to meet the growth of
      their target myotomal muscle. Young adult (260 mm in length), fingerlings (F, 120
      170 mm), fry (Fr, 70 mm) and eleutherembryos (Es, 20-30 mm) of rainbow trout
      (Oncorhyncus mykiss) were employed in this study. PCNA immunohistochemistry was
      used for monitoring the proliferative activity in the epithelium of the spinal
      cord central canal. This activity was quantified as the number of PCNA labelled
      cells for each spinal cord section. In Es and Fry, a mean value of 3-5 labelled
      cells for each section was found with a sharp decrease in young F (120 mm long).
      After this fish length, it was not possible to quantitatively evaluate the
      proliferative activity at the central canal. However, labelled cells were seldom
      found in the spinal cord sections until a fish length of 260 mm. From these data
      it is possible to conclude that motoneurone recruitment in the trout spinal cord
      is down-regulated at the F stage. Afterwards, we found that motoneurones increase
      in size to meet the growth of their target myotomal muscle.

PMID- 11512641
TI  - The history of intravenous anaesthesia: the barbiturates. Part 3.

PMID- 11512642
TI  - Do anaesthetists need to wear surgical masks in the operating theatre? A
      literature review with evidence-based recommendations.
AB  - Many operating theatre staff believe that the surgical face mask protects the
      healthcare worker from potentially hazardous biological infections. A
      questionnaire-based survey, undertaken by Leyland' in 1993 to assess attitudes to
      the use of masks, showed that 20% of surgeons discarded surgical masks for
      endoscopic work. Less than 50% did not wear the mask as recommended by the
      Medical Research Council. Equal numbers of surgeons wore the mask in the belief
      they were protecting themselves and the patient, with 20% of these admitting that
      tradition was the only reason for wearing them. Policies relating to the wearing
      of surgical masks by operating theatre staff are varied. This indicates some
      confusion about the role of the surgical mask in modern surgical and anaesthetic
      practice. This review was undertaken to collate current evidence and make
      recommendations based on this evidence.

PMID- 11512644
TI  - Relationship between work of breathing provided by a ventilator and patients'
      inspiratory drive during pressure support ventilation; effects of inspiratory
      rise time.
AB  - Inspiratory drive and work of breathing provided by a ventilator (WOBv) during
      pressure support ventilation (PSV) were examined in 15 patients. At PSV 10 and 15
      cm H2O during CPAP 5 cm H2O, patients with low P0.1 (<4.2 cm H2O, n=9) showed
      WOBv 0.57 and 0.92 J/l, those with high P0.1 (>4.2 cm H2O, n=6) showed 0.31 and
      0.62 J/l respectively. WOBv was smaller and pressure-time product of oesophageal
      pressure (PTP) was significantly larger in high P0.1 patients. Peak inspiratory
      flow for low P0.1 patients increased as PSV level increased but high P0.1
      patients showed no significant change. In a lung model, effects of inspiratory
      rise time (IRT) and PSV were studied at high and low inspiratory drives by using
      ventilators with (Servo 300) and without (Mallinckrodt 7200a) adjustable IRT.
      With 7200a, PSV 10 cm H2O during low drive was compared with PSV 10 and 15 cm H20
      during high drive. In Servo 300, PSV 10 cm H2O (IRT 0.6 and 0.0 sec) during low
      drive was compared with PSV 10 cm H20 (IRT 0.6 and 0.0 sec) and PSV 15 cm H2O
      (IRT 0.6 sec) during high drive. Raising PSV and shortening IRT both increased
      peak inspiratory flow. Initial inspiratory flow increased in inverse proportion
      to IRT, but higher PSV had a little effect. WOBv with high drive was less than
      with low drive. Higher PSV preserved WOBv by increasing tidal volume. Shortening
      IRT recruited WOBv by increasing initial inspiratory flow without changing airway
      pressure and tidal volume. Compared with higher PSV, shorter IRT reduced PTP
      more. In conclusion, WOBv decreased as inspiratory drive increased due to
      inability to increase inspiratory flow. Increasing initial inspiratory flow was
      more effective than raising PSV to preserve inspiratory assistance of PSV at high
      inspiratory drive.

PMID- 11512643
TI  - Prolonged thiopentone infusion for neurosurgical emergencies: usefulness of
      therapeutic drug monitoring.
AB  - Serial serum thiopentone concentrations were measured during and following
      completion of an intravenous infusion of thiopentone in 20 patients with
      neurosurgical emergencies. The concentration data from a further 55 patients who
      had had some such measurements were reviewed retrospectively. The patients
      received an infusion for longer than 24 hours at a rate adjusted to maintain EEG
      burst suppression. The data were interpreted in terms of thiopentone
      pharmacokinetics and used to produce statistical models relating to clinical
      outcomes. In these patients, the one-month mortality rate following commencement
      of thiopentone treatment was 20%; the mean durations of pupillary and motor
      unresponsiveness following cessation of an infusion were 22 and 91 hours,
      respectively. Predictors of a prolonged duration of motor unresponsiveness
      included a prolonged duration of pupillary unresponsiveness, a low thiopentone
      clearance and a high maximum serum concentration of thiopentone. From pooled
      logistic regression, median effective serum thiopentone concentrations (EC50)
      were found to be 50 mg x l(-1) for recovery of pupillary responsiveness and 12 mg
      x l(-1) for the recovery of motor responsiveness. Because prolonged high-dose
      thiopentone leads to prolonged residual serum concentrations, it is difficult to
      distinguish the residual pharmacological effects of thiopentone from the clinical
      condition. This study suggests that, based on EC50 values for responses,
      monitoring of post-infusion serum thiopentone concentrations may help determine
      whether a patient's clinical state is due to residual thiopentone pharmacological
      effects.

PMID- 11512645
TI  - An evaluation of nitric oxide and nitrogen dioxide absorbers and filters.
AB  - The absorbance of NO (5-90 ppm) and NO2 (0.5-4 ppm) by a number of absorbers and
      filters was assessed via bench testing. All absorbers (Sodasorb, Purafil CP,
      Purafil Select, Sofnolime, Sofnofil and 50/50 mix of Sofnolime/Sofnofil) except
      Sodasorb absorbed NO almost completely. Only Sofnolime absorbed NO2 completely
      while Sodasorb and the Sofnolime/Sofnofil 50/50 mix had absorbances between 47%
      and 90%. The absorbance of four filters (ILF100, ILF150, ILF200 and HgCONO) as
      well as Sofnolime and the Sofnolime/Sofnofil 50/50 mix was tested in the
      expiratory port of a Servo 900C ventilator All absorbers and filters produced a
      change in ventilator pressures. The HgCONO filter Sofnolime and the
      Sofnolime/Sofnofil 50/50 mix all absorbed NO. At 80 ppm NO, the HgCONO filter had
      100% absorbance for four hours while Sofnolime's absorbance was significantly
      reduced after one hour. All filters and absorbers tested on the ventilator except
      the Sofnolime/Sofnofil 50/50 mix and the ILF150 filter absorbed NO2 completely
      for a period ranging from 90 minutes to four hours. We recommend the HgCONO
      filter and Sofnolime to absorb both NO and NO2. If absorption of NO2 only is
      required we recommend the HgCONO, ILF100 or ILF200 filters or the Sofnolime
      absorber.

PMID- 11512646
TI  - Edrophonium antagonism of cisatracurium-induced neuromuscular block: dose
      requirements in children and adults.
AB  - This randomized, controlled study compared edrophonium dose requirements to
      antagonize cisatracurium-induced neuromuscular block in children and adults.
      Sixty children, aged two to 10 years, and 60 adults aged 20 to 60 years, all
      subjects ASA physical status 1 or 2, having propofol, fentanyl and isoflurane-N2O
      anaesthesia, were studied. Cisatracurium 0.1 mg x kg(-1) was given for muscle
      relaxation. Neuromuscular block was monitored with accelerometry. Edrophonium
      0.1, 0.2, 0.4 or 1 mg x kg(-1) or no anticholinesterase (controls) was given by
      random allocation to antagonize 90% neuromuscular block in each of the study
      groups (n=12). Atropine 5 to 10 microg x kg(-1) was given according to
      edrophonium dose. Onset time of cisatracurium-induced block in children was mean
      (SD) 2.4 (0.8) versus 4.1 (2.3) minutes in adults, P<0.01. The times to 10%
      spontaneous recovery of the first twitch (T1) were respectively, 28.4 (5.2) and
      41.8 (6.1) minutes in children and adults, P<0.01. Spontaneous and antagonist
      assisted neuromuscular recovery was more rapid in children. Adequate
      neuromuscular recovery (train of four (TOF) ratio 80%) was achieved in children
      at 3 and 10 minutes after edrophonium 1.0 mg kg(-1) and 0.4 mg x kg(-1),
      respectively. A TOF ratio of 80% was not achieved, within 10 minutes, with any of
      the four dose levels of edrophonium in adults. The dose of edrophonium to achieve
      a TOF ratio of 80% (ED(TOF-80)) after 5 and 10 minutes in children were,
      respectively, mean (SD) 0.85 (0.38) and 0.38 (0.19) mg x kg(-1). The equivalent
      ED(TOF-80) in adults was outside the edrophonium dose range studied.

PMID- 11512647
TI  - Sensitivity of action potential triggering is normally distributed as a function
      of mean fractional receptor activation.
AB  - In 1968, Waud presented his general pharmacodynamic model consisting of two sub
      functions that divide the pharmacodynamic cascade from drug concentration to cell
      effect/response into two successive steps: Step one (the internal function)
      characterizes the binding of agonist drug molecules to the post-synaptic
      receptors and the subsequent receptor activation, and step two (the
      external/effect function) characterizes the cell response induced by a critical
      receptor pool activation. According to Waud, the problem of determining the
      relation between drug concentration and cell response/effect reduces to the
      second step in the pharmacodynamic cascade. In this paper, we suggest a new
      external/effect-function, the cumulative Normal population-effect-function. It
      describes how muscle fibre excitability (all-or-none phenomenon) is distributed
      as a function of mean fractional receptor activation in a muscle fibre
      population. This function fits to empirical data and explains logically why the
      sigmoid muscle effect, from minimal to maximal, is seen in such a narrow range of
      antagonist concentrations and receptor occupancies.

PMID- 11512648
TI  - Intrathecal anaesthesia for the elderly patient: the influence of the induction
      position on perioperative haemodynamic stability and patient comfort.
AB  - Ninety elderly (>65 y) patients were studied to assess the influence of patient
      position during induction of spinal anaesthesia on the incidence of perioperative
      hypotension and haemodynamic stability. Prior to induction of anaesthesia,
      Lactated Ringer's solution (8-10 ml/kg) was administered. In the Sitting Group,
      intrathecal anaesthesia was performed with the patient in the sitting position.
      In the Lateral Group, patients assumed the lateral decubitus position. In all
      cases hyperbaric bupivacaine (10 mg) was administered using a 25 gauge Quincke
      spinal needle. Patients were placed in the supine (and thereafter lithotomy)
      position immediately after withdrawing the spinal needle. Incremental doses of
      ephedrine (5 mg, i.v.) were administered in response to hypotension (>20% of
      baseline), nausea, vomiting, sweating, skin pallor or impaired consciousness. The
      mean arterial blood pressure, heart rate and the number of hypotensive episodes
      requiring ephedrine administration were unaffected by group affiliation. In the
      Sitting Group, nine patients received 24 doses of ephedrine 5 mg i.v. In the
      Lateral Group, 21 incremental doses of ephedrine were administered to nine
      patients. The incidence of nausea, vomiting, sweating and pallor were similar
      between the groups. Patient comfort was similar. In summary, the incidence of
      hypotension and hypotension-related adverse effects was similar when intrathecal
      anaesthesia was induced in the sitting or lateral position. Furthermore,
      subjective perception of the induction process or anaesthetic experience was not
      affected by patient position.

PMID- 11512649
TI  - Tracheal intubation without muscle relaxant--a technique using sevoflurane vital
      capacity induction and alfentanil.
AB  - This randomized controlled study examined intubating conditions and haemodynamic
      changes following sevoflurane nitrous oxide induction in four groups: three
      different doses of alfentanil compared with low-dose alfentanil and
      suxamethonium. All patients received atropine 0.3 mg i.v. before induction of
      anaesthesia with vital capacity breaths of sevoflurane 8% (more than 7% in the
      inspiratory gas) in 60% nitrous oxide and oxygen. Patients were allocated
      randomly to four groups of intravenous supplements: group SA20, alfentanil 20
      microg x kg(-1); group SA25, alfentanil 25 microg x kg(-1); group SA30,
      alfentanil 30 microg x kg(-1); group SSA, alfentanil 10 microg x kg(-1) and
      suxamethonium 1 mg x kg(-1). Orotracheal intubation and assessment of intubating
      conditions was performed by one of the investigators who was blinded to the
      subject's group. Intubating conditions were satisfactory or excellent in 83%,
      80%, 92% and 96% of patients in groups SA20, SA25, SA30 and SSA respectively.
      These differences were not statistically significant. The increase in heart rate
      associated with laryngoscopy and tracheal intubation was effectively attenuated
      in all groups. Mean arterial pressure decreased significantly and similarly after
      induction in all groups. Two minutes after intubation the mean arterial pressure
      was increased significantly (P<0.05) compared to the post-induction value in
      group SSA. The intubating conditions obtained with sevoflurane plus alfentanil 30
      microg x kg(-1) were comparable to those provided by the sevoflurane,
      suxamethonium and alfentanil 10 microg x kg(-1) combination.

PMID- 11512650
TI  - Coagulation studies in preoperative neurosurgical patients.
AB  - Unselected preoperative coagulation testing is known to have low positive yield.
      However, no study has specifically evaluated neurosurgical patients. A
      retrospective study of 1211 patients having neurosurgery over a one-year period
      was therefore conducted. Preoperative test results (activated partial
      thromboplastin time [aPTT], prothrombin time [PT] and platelet count) and
      historical factors indicating a potential bleeding tendency were recorded.
      Abnormality was defined as a test result outside the normal range for our
      laboratory. Seventeen per cent of all test results were abnormal. However, if
      abnormality was redefined as a test result indicating potential bleeding tendency
      (low platelet count, prolonged aPTT and/or PT), only 7.2% of results were
      abnormal. Many patients had factors on history indicating a potential bleeding
      tendency, but only a prolonged aPTT, cranial surgery and the use of anti
      hypertensive and anaesthetic drugs preoperatively predicted postoperative
      bleeding. Prolonged aPTT was predictable on history in most patients. We conclude
      that routine screening of all preoperative neurosurgical patients in our hospital
      is unnecessary.

PMID- 11512651
TI  - Latex hypersensitivity in spinal cord injured adult patients.
AB  - Latex hypersensitivity is a major cause of anaphylaxis during anaesthesia.
      Patients with spina bifida, health care or rubber industry workers have been
      considered at risk for latex sensitization. By analogy, the existence of other at
      risk subsets of patients with latex exposure due to frequent surgical procedures
      has been suggested. The aim of this study was to evaluate the prevalence of latex
      sensitization in a cohort of adult patients with spinal cord injury and repeated
      latex exposure. Forty-two adult patients with spinal cord injury were studied and
      retrospectively compared to a group of 30 children with spina bifida evaluated
      using a similar protocol. Patients were administered a questionnaire concerning
      history of latex hypersensitivity, atopy, and surgical procedures. Latex
      sensitivity was investigated by skin prick-tests and latex-specific IgE assay.
      The search for atopy was based on in vivo and in vitro tests against a panel of
      environmental allergens. No chronic spinal cord injured patient had a history of
      latex allergy. When compared with spina bifida, the number of surgical procedures
      was not statistically different. Although not significantly different, the
      prevalence of atopy was higher in spina bifida patients. The high level of latex
      sensitization in spina bifida patients contrasted sharply with the absence of
      sensitization observed on both skin and in vitro tests in patients with spinal
      cord injury (P<0.0001). This study confirms that adult patients with chronic
      neurologic defects resulting from spinal cord injury exhibit a low risk of latex
      sensitization. These results suggest that considering adult patients with
      repeated surgical procedures as a group at risk for latex sensitization because
      of a high degree of latex exposure should be re-examined.

PMID- 11512652
TI  - Intrahospital transport of critically ill patients: complications and
      difficulties.
AB  - An audit of 97 intrahospital transports of critically ill patients was undertaken
      within Westmead Hospital. The aims of this audit were to assess all factors that
      may lead to problems during intrahospital transports. At the completion of a
      transport medical staff were asked to provide information about their patient and
      their treatment, as well as any difficulties they may have encountered. Overall,
      62% of transports reported some difficulty or complication. Of these, 31% were
      patient-related and 45% were related to equipment or the transport environment.
      (15% encountered problems in both areas). Many of the difficulties were
      preventable with adequate pre-transport communication and planning. Other
      problems were directly related to the increased severity of illness in these
      patients.

PMID- 11512653
TI  - Anaesthetic considerations for patients undergoing hypothermic cardiopulmonary
      bypass for complex neurovascular lesions: case presentation and review.
AB  - The anaesthetic management of a 38-year-old woman having excision of a meningioma
      involving the superior sagittal sinus is described. The procedure was performed
      using low flow moderate hypothermic cardiopulmonary bypass with central
      cannulation. Relevant literature is reviewed.

PMID- 11512654
TI  - General anaesthesia in a patient with undiagnosed "saber-sheath" trachea.
AB  - Saber-sheath trachea describes an abnormality in the shape of the trachea caused
      by underlying disease processes. We present a case of tracheal stenosis in a
      patient with undiagnosed saber-sheath trachea, in which there was unexpected
      difficulty in ventilating the lungs despite a good view at laryngoscopy and
      visually confirmed tracheal intubation.

PMID- 11512655
TI  - Concealed post-tonsillectomy haemorrhage associated with the use of the
      antiemetic tropisetron.
AB  - A two-year-old child experienced concealed haemorrhage after adenotonsillectomy.
      In our patient, the absence of vomited or significant gastric blood and the
      presence of melaena stools may partly be attributed to prophylactic antiemetic
      treatment with tropisetron. This group of patients has a high incidence of
      postoperative nausea and vomiting, and antiemetic treatment is important and
      valuable. Rather than advocating the withholding of prophylactic antiemetic
      treatment, we suggest that whatever medication and techniques are used, good
      clinical care is dependent on careful postoperative observation and assessment
      for an appropriate period of time.

PMID- 11512656
TI  - Awake craniotomy in an adolescent.
AB  - We present our approach to management of awake craniotomy for epilepsy surgery
      for an adolescent. The importance of patient selection and preoperative
      preparation is stressed. Anaesthetic management included regional scalp block and
      preincisional surgical infiltration of local anaesthetic and light sedation with
      propofol, fentanyl and midazolam. The patient remained responsive to voice for
      all but a small part of the procedure.

PMID- 11512657
TI  - Severe falciparum malaria in five soldiers from East Timor: a case series and
      literature review.
AB  - Despite chemoprophylaxis, malaria remains a serious threat for large numbers of
      non-immune soldiers deployed in endemic areas. Five adult cases of severe
      falciparum malaria are reported. Three cases were complicated by multiorgan
      failure and one of these patients died from cerebral malaria. These cases serve
      to highlight issues, in an Australian intensive care unit, associated with the
      management of severe malaria, an uncommon disease in our country. The need for
      rapid diagnosis and commencement of appropriate treatment is paramount in
      preventing further morbidity and mortality. Understanding and management of
      malaria continues to evolve rapidly. The pathophysiology of acute lung injury,
      shock and brain injury associated with malaria are examined in light of recent
      research. This article discusses the current controversies of exchange blood
      transfusion and the use of the new artemisinin derivatives.

PMID- 11512658
TI  - Effects of increasing cardiac output on arterial haemoglobin saturation during
      one-lung ventilation.

PMID- 11512659
TI  - Does adrenaline improve epidural bupivacaine and fentanyl analgesia after
      abdominal surgery?

PMID- 11512660
TI  - Diagnosis of laryngeal oedema before extubation after major neck surgery: use of
      fibreoptic assessment via a laryngeal mask airway.

PMID- 11512661
TI  - Spatial and temporal dynamics of two alternatively spliced regulatory factors,
      lens epithelium-derived growth factor (ledgf/p75) and p52, in the nucleus.
AB  - Regulatory factors, lens epithelium-derived growth factor (LEDGF)/p75 and p52,
      are generated from a single LEDGF gene by alternative splicing. They have
      identical amino acid residues between positions 1-325, but 205 and 8 of the
      remaining residues are different in LEDGF and p52, respectively. LEDGF promotes
      growth and survival of many cell types. It has an antiapoptotic function and is a
      weak general transcriptional co-activator. p52 is a transcriptional activator and
      an essential splicing factor. We investigated the spatial and temporal dynamics
      of LEDGF/p75 and p52, each being tagged with a fluorescent protein, during the
      cell cycles of CHO-K1, MCDK, and NRK cells in culture. Both LEDGF/p75 and p52
      were localized predominantly in the nucleus. LEDGF/p75 was distributed diffusely
      in the nucleoplasm in the G1-phase and attached to chromatin heterogeneously
      during the G2 and M-phases of cells. In contrast, p52 was localized in the
      nuclear periphery during the G1-phase and formed a speckle pattern at the S
      phase. It formed a cylindrical pattern around the chromosomes during the M-phases
      of cells. LEDGF and p52 on sister chromatids migrated into daughter cells. Thus,
      LEDGF/p75 and p52 are localized in distinct nuclear compartments where they can
      activate transcription or splicing of pre-mRNAs.

PMID- 11512662
TI  - Immunohistochemical identification of cholecystokinin A receptors on interstitial
      cells of Cajal, smooth muscle, and enteric neurons in rat pylorus.
AB  - One of the physiological functions of circulating cholecystokinin (CCK) is in the
      control of the pyloric sphincter and the subsequent delivery of nutrients to the
      small intestine. In order to identify the site(s) of action of CCK in the
      gastropyloric region, we performed immunohistochemistry using an antibody
      directed to the C-terminal region of the cholecystokinin A receptor (CCKAR). In
      the rat, cells that display strong CCKAR immunoreactivity and fit the
      morphological description of interstitial cells of Cajal (ICC) were found in the
      distal sphincter muscle and in the circular muscle of the proximal duodenum.
      Double labeling showed that these cells coexpressed vimentin, but that not all
      vimentin-positive cells expressed CCKAR. Confirmation that the CCKAR-expressing
      cells were ICC also came from kit double-labeling experiments in mice. In
      addition to ICC, circular smooth muscle cells at the tip of the comma-shaped
      sphincter muscle, but not elsewhere, also exhibited strong, membrane-bound CCKAR
      immunoreactivity. With higher antibody concentrations, the entire circular muscle
      displayed moderate CCKAR immunoreactivity, suggesting that circular smooth muscle
      cells express low levels of CCKAR. Select neurons in the myenteric ganglia near
      the sphincter muscle proper, the distal antrum, and proximal duodenum, as well as
      a few single neurons in the submucosa, also expressed strong CCKAR
      immunoreactivity. Finally, CCKAR-immunoreactive ICC and neurons were not
      specifically related to vagal afferent intramuscular and intraganglionic endings,
      and vagal afferents themselves did not exhibit any CCKAR immunoreactivity. These
      results suggest a role for ICC and enteric neurons in the mediation of CCK
      effects on pyloric sphincter pressure in addition to direct effects of the
      hormone on circular smooth muscle.

PMID- 11512663
TI  - Immunocytochemical detection of Reissner's fiber-like glycoproteins in the
      subcommissural organ and the floor plate of wildtype and cyclops mutant zebrafish
      larvae.
AB  - The subcommissural organ (SCO) and the floor plate (FP) secrete high molecular
      weight glycoproteins that polymerize in the form of the Reissner's fiber (RF). To
      study to what extent the absence of the FP affects the expression of these
      glycoproteins, we have investigated the brain and spinal cord of 48-h and 72-h
      wildtype and cyclops (cyc) mutant zebrafish larvae by using a polyclonal
      antiserum against bovine RF. Wildtype larvae showed immunoreactivity in the SCO
      at the dorsal forebrain-midbrain boundary. In the ventricle, over the SCO
      surface, thin immunoreactive fibers aggregated into an RF that ran along the
      third and fourth ventricles and the central canal of the spinal cord until, at
      its caudal end, the fiber disintegrated and formed a strongly immunoreactive
      massa caudalis that left the neural tube and invaded the surrounding tissues of
      the tail fin. The rostral end of the FP, lining the pontine flexure, was also
      strongly immunoreactive, as was the caudal third of the FP. Cyc mutants showed an
      immunoreactive SCO and fibrous material in the ventricle, but an RF was missing.
      There was no label in the ventral midline of the neural tube except in some
      specimens in which the caudal FP persisted and was immunoreactive. It is
      concluded that the product of the cyc gene is not required for the expression of
      SCO glycoproteins but for their polymerization into an RF in the brain
      ventricles.

PMID- 11512664
TI  - Calcium not strain regulates localization of alpha-myosin heavy chain mRNA in
      oriented cardiac myocytes.
AB  - Our aim was to test a hypothesis that localization of the alpha-myosin heavy
      chain (alpha-MyHC) mRNA in oriented neonatal rat cardiomyocytes is regulated
      either by calcium, or by mechanical strain, or by both. Myocytes, grown on
      collagen aligned on stretchable silicone membranes, were elongated and had an
      increased length to width ratio (L/W) compared with randomly oriented myocytes
      grown on conventional substrata. Oriented cells were stretched by 10% in the
      longitudinal direction, in the transverse direction or passively unloaded for 6
      h. As expected, shape changes followed these mechanical deformations. In situ
      hybridization was used to determine the localization of alpha-MyHC mRNA by
      quantitative analysis of optical density under various mechanical perturbations
      in myocytes that were either spontaneously beating or treated with verapamil (10
      mM) to block influx of calcium. Unstretched, longitudinally stretched, and cells
      stretched transversely all had mRNA dispersed to their extremities. Verapamil
      treatment resulted in a perinuclear pattern of mRNA under all three mechanical
      perturbations. Additionally, mRNA distribution was examined in myocytes that were
      passively unloaded in the presence and absence of verapamil. Unloading myocytes
      with intact calcium cycling does not result in a perinuclear accumulation of
      mRNA. These data suggest that calcium is essential for alpha-MyHC mRNA
      distribution throughout the cell whereas stretch and alignment affect myocyte
      shape but have little effect on mRNA localization.

PMID- 11512665
TI  - Ultrastructural study of the cuticle and epidermis in Pseudochordodes bedriagae.
AB  - The light-microscopic and ultrastructural characteristics of Nematomorpha
      (Gordiacea) integument are described. Nine male Pseudochordodes bedriagae
      specimens were collected in the 1997 spring-summer period from the Sauce Chico
      stream in the Sierra de la Ventana, province of Buenos Aires, Argentina. Of these
      samples, two were analyzed using scanning electron microscopy (SEM) and the other
      two using transmission electron microscopy (TEM) in order to establish their
      morphological characteristics. The morphology of the three integumentary
      components (epidermis, cuticle and epicuticle) is described. Comparing our
      findings with those of previous studies, numerous similarities are pointed out.
      Some variants found would probably be related more to the various criteria of
      interpreting cut incidences and/or fractures than to actual differences. We
      assume that the different zones of the cuticle and epicuticle are segregated at
      the germinal stratum level by the epidermal cells, which would later undergo a
      slow process of maturation until their exocytosis at the level of the free
      epicuticular surface.

PMID- 11512666
TI  - Distribution of NADPH-diaphorase-positive ascending interneurones in the crayfish
      terminal abdominal ganglion.
AB  - Previous neuropharmacological studies have described the presence of a nitric
      oxide-cGMP signalling pathway in the crayfish abdominal nervous system. In this
      study we have analysed the distribution of putative nitric oxide synthase (NOS)
      containing ascending interneurones in the crayfish terminal abdominal ganglion
      using NADPH-diaphorase (NADPHd) histochemistry. Ascending intersegmental
      interneurones were stained intracellularly using the fluorescent dye Lucifer
      yellow and the ganglia containing the stained interneurones subsequently
      processed for NADPHd activity. Fluorescence persisted throughout histochemical
      processing. These double-labelling experiments showed that 12 of 18 identified
      ascending interneurones were NADPHd positive. Thus many ascending interneurones
      that process mechanosensory signals in the terminal ganglion may contain NOS, and
      are themselves likely sources of NO which is known to modulate their synaptic
      inputs. Three clear relationships emerged from our analysis between the effects
      of NO on the synaptic inputs of interneurones, their output properties and their
      staining for NADPH-diaphorase. First were class 1 interneurones with no local
      outputs in the terminal ganglion, the NE type interneurones, which had sensory
      inputs that were enhanced by NO and were NADPHd positive. Second were class 1
      interneurones with local and intersegmental output effects that had sensory
      inputs that were also enhanced by NO but were NADPHd negative. Third were class 2
      interneurones with local and intersegmental outputs that had synaptic inputs that
      were depressed by the action of NO but were NADPHd positive. These results
      suggest that NO could selectively enhance specific synaptic connections and
      sensory processing pathways in local circuits.

PMID- 11512667
TI  - Retinal development in the lobster Homarus americanus. Comparison with compound
      eyes of insects and other crustaceans.
AB  - Pattern formation and ommatidial differentiation were examined in the developing
      retina of the lobster Homarus americanus using light and electron microscopy. In
      the lobster the retina differentiates from the surface ectoderm that covers the
      optic primordia. Initially a single band of proliferation moves across this
      surface ectoderm. Immediately following this wave of proliferation, rows of
      ommatidial cell clusters appear. The earliest cell clusters are often seen
      adjacent to dividing cells of the proliferation band. The changing organization
      of the first seven rows of ommatidial clusters, visible at the surface of the
      retina, reveals events in early ommatidial differentiation. A rosette-like
      cluster of 18 cells forms the first row. Each stage following the rosette
      clusters occurs in a separate staggered row. Developing ommatidia have a central
      cluster of retinula cells, whose organization changes at each stage. Four cone
      cells enclose the retinula cells in each cluster and extend to the surface. In
      the seventh row, rhabdome formation begins and the retinula cells recede, leaving
      only cone cells visible at the retinal surface. This change initiates the two
      tiered organization of the adult ommatidium. In 70% embryos, asymmetries in the
      position of the R8 axon around R7 create an equatorial line separating the dorsal
      and ventral halves of the retina. Possible mechanisms for the formation of these
      asymmetries are discussed. Postembryonic growth of the retina continues in stage
      VI juvenile animals along the ventral edge of the retina.

PMID- 11512668
TI  - Skeletogenesis in sea urchin interordinal hybrid embryos.
AB  - Reciprocal interordinal crosses were made between the sea urchins
      Strongylocentrotus purpuratus and Lytechinus pictus. Previous research indicated
      that the expression of many L. pictus genes is reduced in the hybrid embryos. The
      S. purpuratus gene encoding the spicule matrix protein SM50 and the L. pictus
      gene encoding its orthologue LSM34 were both expressed at normal levels per gene
      copy in hybrid embryos, and in about 32 skeletogenic primary mesenchyme cells
      (PMCs) in hybrid and natural gastrulae. In many embryos of all crosses, 16 PMCs
      initially ingressed, while 32-64 PMCs were present in gastrulae. The skeletal
      spicules of most hybrid plutei were predominantly like those of S. purpuratus,
      consistent with the predominance of expression of S. purpuratus genes in hybrid
      embryos. The spicules of some hybrid plutei showed features characteristic of L.
      pictus, such as recurrent rods, branched body rod tips, or convergent ventral
      transverse rods; a few hybrid spicules were predominantly like those of L.
      pictus. Based on our observations and the literature, we propose the following.
      Cues from the ectodermal epithelium position the PMCs as they elaborate the
      initial triradiate spicules. Their orientation and outgrowth appears to be
      responsible for the convergence of the tips of body rods in most S. purpuratus
      and hybrid embryos, unlike in most L. pictus embryos. Variations among hybrid and
      natural embryos in skeletal branching pattern reflect differences in
      interpretation by PMCs of patterning cues produced by the ectodermal epithelium
      that probably have similar spatial distributions in the two species.

PMID- 11512669
TI  - Leukocyte recruitment and neuroglial activation during facial nerve regeneration
      in ICAM-1-deficient mice: effects of breeding strategy.
AB  - Intercellular adhesion molecule 1 (ICAM-1) is a widely expressed glycoprotein
      involved in leukocyte extravasation and the interaction of lymphocytes with
      antigen-presenting cells. We examined these aspects of ICAM-1 function in the
      central nervous system after axonal injury in wild-type and ICAM-1-deficient
      mice. ICAM-1 immunoreactivity in the normal mouse facial nucleus was restricted
      to the vascular endothelium. Transection of the facial nerve led to a fast
      upregulation of ICAM-1 on activated microglia in the axotomized facial nucleus
      and the infiltration of ICAM-1-positive lymphocytes. Labeling elsewhere was
      unchanged. In homozygous ICAM-1 mutant mice, ICAM-1 was absent from endothelial
      cells and lymphocytes, but low levels of ICAM-1 were detected on cell membranes
      of reactive microglial cells. Comparison of wild-type animals with homozygously
      bred, ICAM-1-deficient mice showed a reduction of astrocytic and microglial
      activation, massive late axonal sprouting, and decreased lymphocyte infiltration.
      These experiments were repeated in F1 progeny of heterozygous mice on a C57BL/6
      background. Neuroglial activation and lymphocyte infiltration in F1 homozygously
      deficient mice was unaffected compared with wild-type siblings. The invading ICAM
      1-deficient lymphocytes also adhered to the ICAM-1-positive phagocytotic
      microglial cells in the ICAM-1 mutants. No change in the recruitment of
      macrophages and granulocytes into the crushed facial nerve, and no effect on
      axonal regeneration occurred. These data argue against the requirement of
      endothelial ICAM-1 in the recruitment of leukocytes into the crushed peripheral
      nerve or the axotomized facial motor nucleus and stress the importance of
      adequately matched controls in studying the effects of gene deletion in
      experimental animals.

PMID- 11512670
TI  - Calbindin immunoreactivity of enteric neurons in the guinea-pig ileum.
AB  - Previous studies have identified Dogiel type II neurons with cell bodies in the
      myenteric plexus of guinea-pig ileum to be intrinsic primary afferent neurons.
      These neurons also have distinctive electrophysiological characteristics (they
      are AH neurons) and 82-84% are immunoreactive for calbindin. They are the only
      calbindin-immunoreactive neurons in the plexus. Neurons with analogous shape and
      electrophysiology are found in submucosal ganglia, but, with antibodies used in
      previous studies, they lack calbindin immunoreactivity. An antiserum that is more
      effective in revealing calbindin in the guinea-pig enteric nervous system has
      been reported recently. In the present work, we found that this antiserum reveals
      the same population that was previously identified in myenteric ganglia, and does
      not reveal any further population of myenteric nerve cells. In submucosal
      ganglia, 9-10% of nerve cells were calbindin immunoreactive with this antiserum.
      The submucosal neurons with calbindin immunoreactivity were also immunoreactive
      for choline acetyltransferase, but not for neuropeptide Y (NPY) or vasoactive
      intestinal peptide (VIP). Small calbindin-immunoreactive neurons (average profile
      130 microm2) were calretinin immunoreactive, whereas the large calbindin
      immunoreactive neurons (average profile 330 microm2) had tachykinin (substance P)
      immunoreactivity. Calbindin immunoreactivity was seen in about 50% of the
      calretinin neurons and 40% of the tachykinin-immunoreactive submucosal neurons.
      It is concluded that, in the guinea-pig ileum, only one class of myenteric
      neuron, the AH/Dogiel type II neuron, is calbindin immunoreactive, but, in the
      submucosal ganglia, calbindin immunoreactivity occurs in cholinergic, calretinin
      immunoreactive, secretomotor/vasodilator neurons and AH/Dogiel type II neurons.

PMID- 11512671
TI  - Glial-cell-line-derived neurotrophic factor induces nerve fibre formation in
      primary cultures of adrenal chromaffin cells.
AB  - Neurotrophic factors, such as nerve growth factor (NGF), have been shown to
      promote the differentiation of neural crest neuroblasts into sympathetic neurons,
      whereas glucocorticoids promote the endocrine phenotype of adrenal medullary
      chromaffin cells. This pluripotency is preserved to some extent in adult
      chromaffin cells, with NGF and other neurotrophic factors influencing the
      differentiation of these cells. In this study, the effects of glial cell line
      derived neurotrophic factor (GDNF) on explanted chromaffin tissue have been
      investigated. The localization of mRNAs corresponding to the two components of
      the GDNF receptor, GDNF family receptor alpha 1 (GFRalpha1) and Ret, were
      demonstrated in adult adrenal medullary ganglion cells. GFRalpha1 mRNA was
      expressed in explanted chromaffin tissue at levels dependent on the presence of
      serum in the medium but decreased on the addition of blocking antibodies against
      transforming growth factor beta (TGFbeta). However, TGFbeta1 (1 ng/ml) did not
      upregulate GFRalpha1 mRNA expression when added to serum-free medium. GDNF
      induced neurite formation from chromaffin cells, as measured by the ratio of
      neurite-bearing versus total number of chromaffin cells in primary cultures of
      adult adrenal medulla. The most potent dose inducing neurites from chromaffin
      cells was 100 ng/ml GDNF. However, this dose was not as efficient as that seen
      when chromaffin cells were stimulated with NGF (100 ng/ml). Thus, adrenal
      medullary cells express mRNAs for the GDNF receptor components Ret and GFRalpha1,
      increase their expression upon being cultured in serum-containing medium and
      respond to GDNF treatment with an increase in the number of cells that develop
      nerve processes.

PMID- 11512672
TI  - Internodal specializations of myelinated axons in the central nervous system.
AB  - We have examined the localization of contactin-associated protein (Caspr), the
      Shaker-type potassium channels, Kv1.1 and Kv1.2, their associated beta subunit,
      Kvbeta2, and Caspr2 in the myelinated fibers of the CNS. Caspr is localized to
      the paranodal axonal membrane, and Kv1.1, Kv1.2, Kvbeta2 and Caspr2 to the
      juxtaparanodal membrane. In addition to the paranodal staining, an internodal
      strand of Caspr staining apposes the inner mesaxon of the myelin sheath. Unlike
      myelinated axons in the peripheral nervous system, there was no internodal strand
      of Kv1.1, Kv1.2, Kvbeta2, or Caspr2. Thus, the organization of the nodal,
      paranodal, and juxtaparanodal axonal membrane is similar in the central and
      peripheral nervous systems, but the lack of Kv1.1/Kv1.2/Kvbeta2/Caspr2 internodal
      strands indicates that the oligodendrocyte myelin sheaths lack a trans molecular
      interaction with axons, an interaction that is present in Schwann cell myelin
      sheaths.

PMID- 11512673
TI  - Overlapping and differential localization of Bmp-2, Bmp-4, Msx-2 and apoptosis in
      the endocardial cushion and adjacent tissues of the developing mouse heart.
AB  - The bone morphogenetic proteins BMP-2 and BMP-4 and the homeobox gene MSX-2 are
      required for normal development of many embryonic tissues. To elucidate their
      possible roles during the remodeling of the tubular heart into a fully septated
      four-chambered heart, we have localized the mRNA of Bmp-2, Bmp-4, Msx-2 and
      apoptotic cells in the developing mouse heart from embryonic day (E)11 to E17.
      mRNA was localized by in situ hybridization, and apoptotic cells by TUNEL (TDT
      mediated dUTP-biotin nick end-labeling) as well as by transmission electron
      microscopy. By analyzing adjacent serial sections, we demonstrated that the
      expression of Msx-2 and Bmp-2 strikingly overlapped in the atrioventricular canal
      myocardium, in the atrioventricular junctional myocardium, and in the maturing
      myocardium of the atrioventricular valves. Bmp-4 was expressed in the outflow
      tract myocardium and in the endocardial cushion of the outflow tract ridges from
      E12 to E14. Msx-2 appeared in the mesenchyme of the atrioventricular endocardial
      cushion from E11 to E14, while Bmp-2 and Bmp-4 were detected between E11 and E14.
      Apoptotic cells were also detected in the mesenchyme of the endocardial cushion
      between E12 and E14. Our results suggest that BMP-2 and MSX-2 are tightly linked
      to the formation of the atrioventricular junction and valves and that BMP-4 is
      involved in the development of the outflow tract myocardium and of the
      endocardial cushion. In addition, BMP-2, BMP-4 and MSX-2 and apoptosis seem to be
      associated with differentiation of the endocardial cushion.

PMID- 11512674
TI  - Hyaluronan fragments induce the synthesis of MCP-1 and IL-8 in cultured human
      peritoneal mesothelial cells.
AB  - Human peritoneal mesothelial cells (HMC) play an important role in inflammatory
      processes by their ability to produce various cytokines and chemokines, such as
      monocyte chemoattractant protein 1 (MCP-1) and interleukin 8 (IL-8). In this
      study we investigated the effect of experimentally generated hyaluronan (HA)
      fragments, degradation products of the extracellular matrix component hyaluronan,
      which accumulate at inflammatory sites, on the expression of MCP-1 and IL-8 in
      cultured HMC. MCP-1 and IL-8 mRNA expression was determined by RNase protection
      assays, and protein levels in the supernatants were measured by enzyme-linked
      immunosorbent assays. HA fragments with a molecular mass of approximately 1
      7x10(5) daltons upregulate MCP-1 and IL-8 synthesis in HMC dose and time
      dependently. The effect of HA fragments could be blocked by Ro31-8220, a specific
      protein kinase C inhibitor, and by PD98059, an inhibitor of the mitogen-activated
      protein kinase/extracellular signal-regulated kinase pathway. Upregulation of
      chemokine synthesis was preceded by an increase in NF-kappaB and AP-1 DNA-binding
      activity, suggesting that these transcription factors are activated to increase
      MCP-1 and IL-8 expression by HA fragments. These data demonstrate that HA
      fragments markedly enhance the mRNA expression and protein synthesis of MCP-1 and
      IL-8 in HMC. In concert with previous findings, our observations indicate that
      enhanced levels of HA, which are present in the peritoneal cavity of peritoneal
      dialysis patients, may account for a locally increased chemokine production.

PMID- 11512675
TI  - Fibrillogenic C-terminal fragment of alpha-1-antitrypsin activates human
      monocytes via oxidative mechanisms.
AB  - Production of alpha-1-antitrypsin by human monocytes is an important factor in
      controlling tissue damage by proteases in the microenvironment of inflammation.
      Increases of four- to eightfold in levels of native and fragmented forms of alpha
      1-antitrypsin have been detected in inflammatory loci in vivo. In this study we
      have extended our previous observation that the carboxyl-terminal peptide (C-36)
      of alpha-1-antitrypsin produced by specific proteinase cleavage, when added in
      its fibrillar form at concentrations of 5 microM or more to monocytes in culture,
      induces cytotoxic effects. Experiments with synthetic amyloid-forming peptides
      suggest fibril cytotoxicity to be mediated via a common oxidative stress
      mechanism. We undertook to determine whether C-36 fibril cytotoxicity also
      involves this common pathway. Monocytes stimulated with C-36 fibrils for 1 h
      showed significant elevation in monocyte chemoattractant protein-1 expression,
      induced reduced nicotinamide-adenine dinucleotide phosphate oxidase activity,
      increased intracellular lipid peroxidation, altered mitochondrial membrane
      potential, and increased cytosolic cytochrome c and caspase-3 activity. Treatment
      of monocytes with C-36 fibrils after 24 h also resulted in increased cytosolic
      cathepsin D activity, suggesting that lysosomes may also be destabilized over
      longer periods of time. In contrast, native alpha-1-antitrypsin only showed
      concentration and time-dependent effects on chemoattractant protein-1 expression,
      and these appear to be independent of oxidative stress. These results indicate
      that the cytotoxicity of the fibrillar fragment is mediated via oxidative
      mechanisms and support important multiple roles for native and also for cleaved
      forms of alpha-1-antitrypsin in monocyte recruitment and activation during
      inflammatory processes such as atherosclerosis.

PMID- 11512676
TI  - A 60-kDa protein abundant in adipocyte caveolae.
AB  - To search for caveolar proteins, mice were immunised with rat adipocyte
      membranes. Hybridoma supernatants were screened for antibodies to proteins on the
      cytosolic face of caveolae by indirect immunoelectron microscopy of immunogold
      labelled adipocyte plasma membrane sheets adsorbed on electron-microscope (EM)
      grids. One of the hybridoma supernatants (2F11) produced a specific labelling of
      caveolae which was much more intense than that obtained with caveolin-1
      antibodies. In Western blots of sodium dodecyl sulphate polyacrylamide gel
      electrophoresis (SDS-PAGE) separated proteins in crude membrane fractions from
      different rat tissues, 2F11 labelled a band corresponding to 60 kDa. The
      intensity of 2F11 labelling was high in adipose tissue and in other tissues
      varied in parallel to caveolin- labelling. In blots of plasma membrane (PM) and
      light-microsomal (LM) fractions from a homogenate of adipocytes, prior insulin
      stimulation of the adipocytes translocated GLUT-4 from the LM to the PM fraction,
      but was without effect on the distribution of the 60-kDa protein labelled by
      2F11. Digestion with endoproteinase lys-C produced the same pattern of
      immunoreactive fragments of the protein in the vesicular PM and LM fractions,
      indicating similar membrane topology of the 2F11-reactive, 60-kDa protein in
      vesicles of PM and LM fractions.

PMID- 11512677
TI  - Mitochondrial DNA analysis reveals substantial Native American ancestry in Puerto
      Rico.
AB  - To estimate the maternal contribution of Native Americans to the human gene pool
      of Puerto Ricans--a population of mixed African, European, and Amerindian
      ancestry--the mtDNAs of two sample sets were screened for restriction fragment
      length polymorphisms (RFLPs) defining the four major Native American haplogroups.
      The sample set collected from people who claimed to have a maternal ancestor with
      Native American physiognomic traits had a statistically significant higher
      frequency of Native American mtDNAs (69.6%) than did the unbiased sample set
      (52.6%). This higher frequency suggests that, despite the fact that the native
      Taino culture has been extinct for centuries, the Taino contribution to the
      current population is considerable and some of the Taino physiognomic traits are
      still present. Native American haplogroup frequency analysis shows a highly
      structured distribution, suggesting that the contribution of Native Americans
      foreign to Puerto Rico is minimal. Haplogroups A and C cover 56.0% and 35.6% of
      the Native American mtDNAs, respectively. No haplogroup D mtDNAs were found. Most
      of the linguistic, biological, and cultural evidence suggests that the Ceramic
      culture of the Tainos originated in or close to the Yanomama territory in the
      Amazon. However, the absence of haplogroup A in the Yanomami suggests that the
      Yanomami are not the only Taino ancestors.

PMID- 11512678
TI  - Y-chromosome differentiation in Northwest Africa.
AB  - Variation of seven Y-chromosomal DNA polymorphisms, one microsatellite (DYS19),
      and six biallelic markers (DYS287, DYS271, SRY-2627, SRY-1532, 92R7, and M9),
      were studied in males from Northwest Africa. To evaluate the degree of
      differentiation in this region, males from neighboring areas such as the Iberian
      Peninsula and sub-Saharan Africa were also typed. The results show a large number
      of paternal lineages of Northwest African origin (over 75%), supporting a long
      term population continuity in the area. When the analysis of molecular variance
      (AMOVA) was performed both on the microsatellite and biallelic marker
      combinations or haplogroups, a large degree of differentiation among areas was
      revealed. In spite of these geographic differences, some gene flow between areas
      was detected by the presence of haplogroups with other geographical origins.

PMID- 11512679
TI  - Allele frequencies for candidate genes in atherosclerosis and diabetes among
      Trinidadian neonates.
AB  - Trinidadians of South Asian origin have a high prevalence of cardiovascular
      disease and diabetes compared to Trinidadians of African origin. The degree to
      which these differences are related to genetic and/or environmental factors is
      unclear. To determine whether there might be a genetic basis for this difference
      in prevalence of deleterious phenotypes we examined allele frequencies for
      candidate genes in atherosclerosis and diabetes. We genotyped 81 consecutive
      neonates of African origin and 103 consecutive neonates of South Asian origin. We
      evaluated common polymorphisms in 11 candidate genes for atherosclerosis and
      diabetes. We found differences between the two subpopulations in the allele
      frequencies of several candidate genes, including APOE, LIPC, APOC3, PON1, PON2,
      and PPP1R3. However, the differences in the allele frequencies were not all
      consistent with the pattern of CHD expression between these two ethnic groups in
      adulthood. Thus, differences in genetic architecture alone may not explain the
      wide disparities in disease prevalence between these two subpopulations. It is
      very likely that environmental factors, or unmeasured genetic factors, influence
      the genetic susceptibility to disease in these subpopulations.

PMID- 11512680
TI  - Towards a complete North American Anabaptist Genealogy II: analysis of
      inbreeding.
AB  - We describe a large genealogy data base, which can be searched by computer, of
      295,095 Amish and Mennonite individuals. The data base was constructed by merging
      our existing Anabaptist Genealogy Database 2.0 containing approximately 85,000
      individuals with a genealogy file containing approximately 242,000 individuals,
      kindly provided by Mr. James Hostetler. The merging process corrected thousands
      of inconsistencies and eliminated hundreds of duplicate individuals. Geneticists
      have long been interested in Anabaptist populations because they are closed and
      have detailed written genealogies. The creation of an enlarged and unified data
      base affords the opportunity to examine inbreeding trends and correlates in these
      populations. We show the following results. The frequency of consanguineous
      marriages shows steady increase over time and reached approximately 85% for
      individuals born in 1940-1959. Among consanguineous marriages, the median kinship
      coefficient stayed stable in the 19th century, but rose from 0.0115 to 0.0151 in
      the 20th century. There are statistically significant associations (p < 0.0001)
      between inbreeding and family size and interbirth intervals in the 20th century.
      There is an association (p < 0.0005) between inbreeding and early death for
      individuals born in 1920-1959. However, this association reverses dramatically (p
      < 0.0005 in the opposite direction) for individuals born in 1960-1979. We tested
      for an association between inbreeding and being the mother of twins, but found
      none.

PMID- 11512681
TI  - Local differences in the Archbishopric of Santiago de Compostela (Galicia, Spain)
      in relation to the consanguinity structure, 1900-1979.
AB  - The microgeographic variability of consanguinity in the Archbishopric of Santiago
      de Compostela (Galicia) between 1900 and 1979 was studied. This Archbishopric
      covers 106 local councils integrated by 964 parishes, of which 677 (70.23%) were
      analyzed. Of the 307,094 marriages counted within this period, 15,739
      corresponded to weddings between biologically related couples. Within the
      Archbishopric, eight geographical regions were considered: six coastal regions
      (Golfo Artabro, Bergantinos, Fisterra, Xallas, Santiago Oeste, and Rias Baixas)
      and two inland regions (Santiago Este and Terra de Montes). In order to evaluate
      the differences and similarities among them, the frequencies of all types of
      marriages (consanguineous and nonconsanguineous) were considered. First, a
      hierarchical grouping of the regions based on their chi-squared distances was
      performed. Then, in order to analyze relationships that are exclusively due to
      the structure of consanguinity, a correspondence analysis was performed and only
      the frequency of the different types of consanguineous marriages was taken into
      account. The results from both statistical analyses indicate special features of
      the Xallas region, both in the level of inbreeding (8.75%, the highest in the
      Archbishopric) and in the structure of consanguinity, for which a high proportion
      of uncle-niece marriages was found (6.22% of all consanguineous marriages). In
      all cases the structure of consanguinity provides informative nuances on the
      differences and similarities among population groups.

PMID- 11512682
TI  - Stillbirth pattern in an isolated mediterranean population: La Alpujarra, Spain.
AB  - This study attempted to analyze the effect of several factors on the stillbirth
      pattern in a relatively isolated rural population, La Alpujarra (Spain), during
      the first half of the 20th century. The study was a retrospective analysis from a
      total sample of 2199 births to 525 mothers, allowing for birth year of mother,
      maternal age, parental inbreeding, family size, birth order, sex, single/twin
      delivery, and birth interval. Binomial probability distribution of stillbirths
      provided no evidence for any significantly increased risk in relation to family
      size. Analysis of covariance (ANCOVA) of stillbirth risk in affected families
      indicated a significant effect for sex of the child, parental consanguinity, and
      birth year of mother. Logistic regression showed increased risk in twin delivery
      and pregnancy order one, but not for birth order other than one. Multivariate
      analysis of variance (MANOVA) testing for differences between affected and
      unaffected families supported a temporal decrease of stillbirths during the
      period studied. Although the birth interval average was significantly shorter in
      affected families (p < 0.0001), this association did not hold, in a more detailed
      analysis, for individual intervals in these families (p = 0.20). There was no
      significant effect of maternal age on stillbirths in the whole sample or limited
      to first pregnancies. These results suggest that birth order one and twin
      delivery were the main determinants of the stillbirth pattern in La Alpujarra.
      Furthermore, our data indicate that the decline in stillbirth rate began before
      medical facilities for perinatal care became available, which was not until after
      1950. The temporal decrease in stillbirth rates may therefore be related to an
      increasing social attention to deliveries rather than to prenatal care medical
      facilities.

PMID- 11512683
TI  - Absence of the 9-bp deletion of mitochondrial DNA in pre-Hispanic inhabitants of
      Argentina.
AB  - We investigated the incidence of the Region V mitochondrial DNA 9-base-pair (bp)
      deletion from human remains recovered from several archaeological sites and
      contexts throughout Argentina. Of the 34 samples analyzed, 24 yielded DNA
      extractions that gave clear amplification results. All of the individuals carried
      two repeats of the 9 bp, one of which has been shown to be deleted in some
      individuals of Asian origin and defines mitochondrial lineage B. Although most of
      the modern Amerindian groups in the region exhibit the deletion in high
      frequencies, the absence of the 9-bp deletion among ancient populations of South
      America seems to be the rule rather than the exception, as was reported by
      several studies involving extinct populations. The evidence gathered until now
      suggests that the earliest settlers of this region of South America did not carry
      mitochondrial lineage B.

PMID- 11512684
TI  - Protection afforded by sickle-cell trait (Hb AS): what happens when malarial
      selection pressures are alleviated?
AB  - A study of reproductive outcome in Mobile, AL was conducted among a large
      maternal cohort with sickle-cell disease (Hb SS), sickle-cell trait (Hb AS), and
      no hemoglobinopathies (Hb AA). It was found that mean gravidity and live births
      among Hb AS women were significantly higher than among Hb AA women. These
      findings were surprising since it is generally held that once malarial pressure
      is alleviated, any reproductive advantage that might be conferred by Hb AS would
      disappear and fertility levels would reach levels similar to or slightly less
      than that of Hb AA women. A search of the literature was subsequently conducted
      and a large cohort study of an African-derived population was found in the United
      Kingdom. Results from this study also showed that parity was significantly higher
      among Hb AS women compared to Hb AA women. If survivorship is similar among Hb AS
      and Hb SS women, findings from these two studies raise doubts whether directional
      selection is occurring against the Rb S allele in nonmalarial environments.
      Balancing selection may still be occurring.

PMID- 11512685
TI  - Association of the CHE2 locus with body mass index and butyrylcholinesterase
      activity.
AB  - The butyrylcholinesterase (BChE; EC 3.1.1.8) activities of two electrophoretic
      bands of the CHE2 C5+ phenotype--C5 and C(OF) (other forms)--were quantified by
      densitometry in 100 individuals. The activity data suggested that, in addition to
      determining C5, the CHE2*C5+ allele also increases the level of other BChE forms.
      Since the relative activity of C5 showed the highest correlation coefficient with
      weight when compared with the other BChE activity variables (total, absolute C5,
      and absolute C(OF)), its median activity level was used for the classification of
      CHE2 C5+ phenotypes (faint and intense). Mean body mass index (BMI) was compared
      among the CHE2 locus phenotypes-controlled by sex, age, and ethnic group. It was
      shown that the intense CHE2 C5+ phenotype presents a significantly lower (p <
      0.001) mean BMI (23.2) than the other phenotypes (faint CHE2 C5+ = 25.2; CHE2 C5-
      = 25.4). It seems that the relative COF activity is positively associated with
      fat storage, since CHE2 C5- and faint CHE2 C5+ phenotypes showed higher mean BMI
      than the intense CHE2 C5+ phenotype. Our hypothesis is that the presence of C5 in
      a relatively high proportion leads to less fat storage.

PMID- 11512686
TI  - Consanguineous marriage among the Fulani.
AB  - The Fulani are a broad ethnic category of nomadic and seminomadic pastoralists
      and agropastoralists living in the semiarid Sahel region of sub-Saharan Africa.
      The Fulani are patrilineal, patrilocal, and moderately polygynous, with arranged
      first marriages accompanied by the payment of bridewealth, ideally in the form of
      cattle. Consanguineous marriage is frequent, with first or second cousin marriage
      preferred. In this paper we present data on levels of consanguineous marriage
      among the Fulani of northern Burkina Faso and test the hypothesis that inbreeding
      may be more frequent when there is a scarcity of cattle available, since
      bridewealth demands are thought to be reduced with close-kin marriage. Among 308
      women's marriages, 203 (65.8%) were between kin up to and including second
      cousins, and 102 (33.1%) were between nonkin. Among 276 men's marriages, 196
      (71.0%) were between kin up to and including second cousins, and 77 (27.9%) were
      between nonkin. The mean population inbreeding coefficient (alpha) was 0.0355 for
      women, and 0.0374 for men. No increase was found in population levels of
      inbreeding estimated from marriages contracted after the droughts of 1973 and
      1984, which drastically reduced the Fulani's cattle stocks. However, a
      significantly higher rate of consanguineous marriage was found in families owning
      the fewest cattle.

PMID- 11512687
TI  - John Graunt, John Arbuthnott, and the human sex ratio.
AB  - John Graunt was the first person to compile data that showed an excess of male
      births over female births. He also noticed spatial and temporal variation in the
      sex ratio, but the variation in his data is not significant. John Arbuthnott was
      the first person to demonstrate that the excess of male births is statistically
      significant. He erroneously concluded that there is less variation in the sex
      ratio than would occur by chance, and asserted without a basis that the sex ratio
      would be uniform over all time and space.

PMID- 11512688
TI  - Slow coronary flow: a distinct angiographic subgroup in syndrome X.
AB  - Patients evaluated for chest pain with angiographically normal coronary arteries
      are usually labelled syndrome X. A portion of these patients may not have a
      cardiac cause for their symptoms. The authors aimed to study a subset within this
      group who showed the phenomenon of slow coronary flow (SCF) as evidenced by a
      slow antegrade progression of the dye on the coronary arteriogram to see if this
      could be used as a marker of myocardial ischemia. This observational study
      included 207 patients being evaluated for suspected coronary artery disease and
      found to have normal coronary angiograms. SCF was seen in 49 of these patients
      (23.7%) while the remaining 158 (76.3%) had normal coronary flow (NCF), as
      detected by the corrected thrombosis in myocardial infarction (TIMI) frame count
      method (TIMI frame count more than 2 SD of normal). Forty of the 49 patients
      (82%) in the SCF group had classical angina as compared with only 51 of the 158
      patients (32%) in the NCF group (p<0.01). Also, a definitively positive exercise
      test was observed more commonly in the SCF group than in the NCF group (71% vs
      42%, p < 0.01). The authors conclude that SCF patients constitute a definite
      subset within the wide spectrum of syndrome X and that the phenomenon of SCF
      could be used as a marker for myocardial ischemia.

PMID- 11512689
TI  - Predictive value of mitral annular calcification for the diagnosis of coronary
      artery disease in patients with dilated cardiomyopathy.
AB  - Mitral annulus calcification (MAC) is an independent predictor of coronary artery
      disease (CAD). The present study was designed to determine whether an association
      exists between MAC and CAD in patients with dilated cardiomyopathy. Among the 286
      patients with MAC on echocardiographic examination who underwent coronary
      angiography, 55 patients with echocardiographic findings of dilated
      cardiomyopathy (group I) were compared to 60 age-matched controls without MAC and
      an echocardiographic diagnosis of dilated cardiomyopathy (group II) who underwent
      coronary angiography during the same time. There were no differences in
      echocardiographic findings between two groups. The prevalence of CAD was higher
      in group I when compared to group II (74% vs 28%, p<0.001). With regard to
      severity of CAD, two-vessel, three-vessel, and left main coronary artery disease
      were found to be significantly frequent in group I (p<0.001). Multivariate
      analysis revealed that MAC (p=0.001), diabetes mellitus (p=0.048), and history of
      anginal chest pain (p=0.009) are the independent predictors for the presence of
      CAD in patients with dilated cardiomyopathy. In conclusion, MAC may be a marker
      for the presence of coronary artery disease in patients with dilated
      cardiomyopathy.

PMID- 11512690
TI  - Anomalous circumflex coronary artery: benign or predisposed to selective
      atherosclerosis.
AB  - Anomalous origin of the circumflex coronary artery from the right sinus of
      Valsalva is the most common coronary anomaly and is usually considered benign.
      Although several researchers in the past believed that aberrancy predisposes this
      vessel to accelerated atherosclerosis, this could not get wide acceptance owing
      to lack of convincing data. To examine the suggestion that atherosclerosis
      affects the anomalous circumflex artery more severely, the authors reviewed the
      clinical and angiographic features of patients with this anomaly identified from
      2,684 coronary angiography procedures performed between January 1998 and March
      2000 at their institution. The degree of atherosclerotic narrowing in the
      anomalous artery was compared with that in other coronary arteries in the same
      patient as well as in the nonanomalous circumflex arteries in controls. For
      comparison 3 control subjects were selected for each patient with anomalous
      circumflex artery, matched by age, sex, and clinical presentations. The results
      showed earlier and greater degree of atherosclerotic narrowing of the anomalous
      artery as compared to the other coronary arteries in the same patients as well as
      to nonanomalous circumflex arteries of age- and gender-matched control subjects
      with similar clinical characteristics. However, this predilection for
      atherosclerosis was evident only in anomalous vessels arising from the right side
      and pursuing a retroaortic course. The anomalous artery was responsible for
      myocardial infarction in 3 patients, all of whom were 60 years or older. Two of
      the patients with this anomaly and myocardial infarction underwent successful
      angioplasty with stent placement for symptomatic relief.

PMID- 11512691
TI  - Late systolic wave on brachial artery blood flow velocity pattern in patients
      with coronary artery disease and its relation to vascular stiffness.
AB  - Duplex-Doppler study typically exhibits triphasic brachial artery blood flow
      velocity pattern in subjects classified as normal without clinically evident
      atherosclerotic complications, heart disease, hypertension, or diabetes mellitus.
      In this study, the authors described the late systolic wave on the brachial
      artery blood flow velocity pattern in patients with coronary artery disease and
      investigated the relation between late systolic wave and vascular stiffness.
      Blood flow profile and velocity of the brachial artery were determined
      noninvasively by ultrasound pulsed-Doppler technique under the guidance of a B
      mode ultrasound image in 96 patients with coronary artery disease (CAD). The
      control group consisted of 23 healthy subjects with no or maximally 2 risk
      factors (only among age, cigarette smoking, obesity, and gender) for vascular
      disease. None of the patients and controls had clinical evidence of arterial
      disorders at upper extremities. In 32 patients (33%) with CAD, a late systolic
      wave was observed in the brachial artery Doppler study. On the other hand, no
      late systolic wave was observed in the healthy subjects. In addition, multivessel
      disease, hypertension, advanced age, diabetes, and smoking were significantly
      more frequent in patients with the late systolic wave. In conclusion, peripheral
      arterial abnormalities induced by vascular stiffness may produce alterations in
      regional wave reflections, and the normal triphasic pattern of the brachial
      artery blood flow may change by the appearance of the late systolic wave.

PMID- 11512692
TI  - Alcohol consumption and risk for increased aortic pulse wave velocity in middle
      aged Japanese men.
AB  - A 9-year longitudinal study was performed to prospectively examine the
      association of alcohol consumption with development of increased aortic pulse
      wave velocity (PWV) in 1,358 Japanese men aged 35 to 59 years with a PWV less
      than 8.0 m/sec and without antihypertensive medication. Three hundred fifty-nine
      men developed increased aortic PWV of 8.0 m/sec or more during 10,598 person
      years follow-up. After controlling for potential predictors of aortic PWV, the
      relative risk for increased aortic PWV compared with that in nondrinkers was 1.05
      (95% confidence interval [CI], 0.70 to 1.58) for those who drank 0.1 to 22.9
      g/day of ethanol, 1.58 (95% CI, 0.89 to 1.91) for those who drank 23.0 to 45.9
      g/day of ethanol, 1.77 (95% CI, 1.24 to 2.53) for those who drank 46.0 to 68.9
      g/day of ethanol, and 1.81 (95% CI, 1.23 to 2.66) for those who drank 69.0 or
      more g/day of ethanol (p for trend <0.001). The relative risk for increased
      aortic PWV in current drinkers vs nondrinkers was stronger among men with a body
      mass index (BMI) less than 24.2 kg/m2 and nonsmokers than among men with a BMI
      24.2 kg/m2 or more and current smokers, respectively. These results suggest that
      alcohol consumption is closely associated with risk for increased aortic PWV in
      middle-aged Japanese men.

PMID- 11512693
TI  - Two-dimensional echo Doppler findings in juvenile and adult onset ankylosing
      spondylitis with long-term disease.
AB  - The authors' objective was to determine by 2-dimensional echo Doppler (2DECHO)
      the cardiac abnormalities in juvenile onset ankylosing spondylitis (JOAS) and
      adult onset ankylosing spondylitis (AOAS) in male patients with long-term
      disease. Twenty patients with JOAS, 31 with AOAS, and 20 healthy controls of the
      same age and gender without cardiopulmonary symptoms were studied. Using 2DECHO,
      the heart dimensions were determined according to American Society of
      Echocardiography guidelines. The left ventricle ejection fraction (LVEF) was
      calculated by Teichholz's formula. Cardiomyopathy was established when 2DECHO had
      diminished LVEF. Statistics used were the Student t and Fisher test, chi2, and
      ANOVA. Ninety percent of JOAS and 51% of AOAS patients were B27+ (p=0.005). The
      disease duration was 19.3 +/- 8.8 years in JOAS and 14.8 +/- 12.8 years in AOAS
      (p=NS). Age at the time of the study was 30.7 +/- 9.9 years in JOAS vs 40.3 +/-
      12.7 in AOAS (p=0.003), and vs 40.2 +/- 17 years in controls (p=NS). There was a
      higher frequency of cardiomyopathy in AOAS (32.2%) than in JOAS (25%) and the
      controls (0%) (p=0.01). Patients with JOAS had a higher mitral valve gradient
      (25%) than AOAS patients (19%, p=NS) and controls (0%, p=0.04). Abnormal aortic
      ring reflectance was shown in 19% of AOAS vs 0% abnormalities in JOAS and
      controls (p=0.01). The aortic root diameter was increased in 58% of AOAS, 30% of
      JOAS, and 0% of controls (p=0.001). The frequency of 2DECHO abnormalities was
      increased in cardiopulmonary asymptomatic spondylitis patients. Despite the high
      frequency of B27+, JOAS had a lower frequency of aortic abnormalities than AOAS.
      Mitral valve gradient was found in JOAS and in AOAS that could contribute to a
      decreased ejection fraction and to left ventricular dysfunction.

PMID- 11512694
TI  - Accelerated atherosclerosis in tertiary syphilis and successful treatment with
      saphenous vein grafting--a case report.
AB  - A 48-year-old male patient having none of the known risk factors for
      atherosclerosis underwent coronary artery bypass graft (CABG) surgery because of
      double-vessel coronary artery disease. During the operation, the aorta, both
      internal thoracic arteries (L/R-ITA), and the femoral artery were sclerotic, and
      CABG was performed using only saphenous vein grafts. A diagnosis of tertiary
      syphilis had been confirmed by either microscopic or serologic tests. There were
      different degrees of sclerosis in different arteries of different sizes. The
      presence of coronary artery disease with no known atherosclerotic risk factors
      should include preoperative testing for connective tissue disorders, chronic
      inflammatory disease, and cold hemagglutinins, because of the possible use of
      obligatory deep hypothermia or total circulatory arrest due to a diseased
      ascending aorta.

PMID- 11512695
TI  - Dipyridamole-induced ST-segment elevation indicative of transmural myocardial
      ischemia--a case report.
AB  - Dipyridamole nuclear myocardial perfusion test is a safe and effective
      alternative to exercise nuclear perfusion testing for detecting myocardial
      ischemia. It is the procedure of choice in selected patients who are unable to
      exercise adequately. Intravenous dipyridamole causes coronary vasodilation with
      resultant maldistribution and heterogeneity of coronary flow in the presence of
      significant coronary artery disease. True ischemia, causing symptoms or ST
      segment depression, is uncommon, in part because there is no increase in
      myocardial oxygen demand. A patient in whom myocardial ischemia developed,
      manifested by ST-segment elevation, during dipyridamole stress testing is
      described. Scintigraphic images illustrated a myocardial perfusion defect, which
      was consistent with coronary angiographic findings. This case report addresses
      the importance of dipyridamole-induced ST-segment elevation, its correlation with
      angiographic findings, and the need for continued hemodynamic and
      electrocardiographic monitoring in patients following dipyridamole infusion.

PMID- 11512696
TI  - Coronary artery spasm-induced paroxysmal atrial fibrillation--a case report.
AB  - Paroxysmal atrial fibrillation is described in a patient that was consistent with
      the clinical history developed after induction of coronary artery spasm. The
      mechanism appeared to be sinus node artery spasm inducing sinus node ischemia.
      Coronary artery spasm can be a cause of paroxysmal atrial fibrillation.

PMID- 11512697
TI  - Second primary cardiac B-cell lymphoma after radiation therapy and chemotherapy-
      a case report.
AB  - A 76-year-old man was found to have esophageal squamous cell carcinoma and had
      been treated with radiational therapy and chemotherapy. Five years later, he was
      readmitted with dyspnea and marked edema of his extremities and face. An
      echocardiographic examination revealed a mass lesion in the pericardium with
      pericardial effusion behind the left ventricular posterior wall, which was near
      the site of the original esophageal cancer. Coronary arteriography revealed a
      feeder artery to the mass from the left circumflex branch. No findings indicated
      a recurrence of the esophageal cancer; cytologic studies showed malignant
      lymphoma cells of B-cell origin. A second primary cancer of some organs including
      blood cells might be induced by the carcinogenic effects of ionizing radiation or
      chemotherapeutic agents. This is the first case of second primary cardiac B-cell
      lymphoma after combination therapy.

PMID- 11512698
TI  - Cardiac imaging in a patient with anomalous origin of the left coronary artery
      from the pulmonary artery--a case report.
AB  - Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA)
      is an uncommon congenital heart disease and has a high mortality rate in infancy.
      However, myocardial ischemia does not develop until adolescence or adulthood in
      about 10% of patients. Moreover, the diagnosis of ALCAPA is often difficult in
      cases without heart murmur or cardiac symptoms. The authors report the case of a
      31-year-old man with ALCAPA. He was admitted to the hospital for evaluation of
      mild shortness of breath at exercise, but he had no typical chest symptoms due to
      myocardial ischemia or heart failure until age 31 and he had no heart murmur.
      Moreover, electrocardiogram did not show an old myocardial infarction or
      myocardial ischemia. Therefore, the authors did not suspect ALCAPA until they
      performed transthoracic echocardiography and exercise-stress single photon
      emission computed tomography (SPECT) with Tc-99m-tetrofosmin. The final diagnosis
      was established from the results of coronary arteriography. In the present case,
      a transthoracic echocardiogram showed abnormal coronary circulation, and exercise
      stress SPECT revealed reversible myocardial ischemia. Transthoracic
      echocardiography and myocardial SPECT imaging could be a useful noninvasive tools
      for diagnosing the ALCAPA.

PMID- 11512699
TI  - Self-drainage lymphatic technique.
AB  - About 100 million people around the world have lymphedema; however, a large
      number do not have access to any kind of treatment. The current study reports on
      a technique of lymphatic self-drainage. The method consists of utilizing rods,
      bars, or any cylindrical object that rolls smoothly over the skin area to be
      drained. During this gliding motion a pressure of around 30 to 40 mm Hg should be
      exerted by the patient. The classical concepts of lymphatic drainage should be
      followed. This new method was subjected to a lymphoscintigraphic, anthropometric,
      and clinical evaluation demonstrating its usefulness in treating lymphedema.

PMID- 11512700
TI  - X-ray absorption near-edge structure (XANES) spectral changes of 2-deoxy-D-ribose
      by irradiation within the energy region around the oxygen K-shell absorption
      edge.
AB  - The physicochemical characteristics of 2-deoxy-D-ribose moieties in DNA strands
      are important to understand biological radiation stress. So, the X-ray absorption
      near edge structure (XANES) of 2-deoxy-D-ribose within the energy region around
      the oxygen K-shell absorption edge was measured. 2-deoxy-D-ribose was exposed to
      3 energies of X-rays, i.e., 526.3 eV (below O 1s-->pi*), 537.8 eV (at the
      absorption peak of O 1s-->sigma*) and 552.6 eV (above O 1s-->sigma*) for given
      periods. Slight differences in spectral changes were seen in the each irradiation
      energy, suggesting in fact that the chemical state and following rearranged
      chemical structure of 2-deoxy-D-ribose may be different between the 3 irradiation
      energies.

PMID- 11512701
TI  - HF-STEX and RASSCF calculations on nitrogen K-shell X-ray absorption of purine
      base and its derivative.
AB  - The nitrogen K-shell X-ray absorption spectra of the purine bases present in
      nucleic acids, adenine and guanine, were analyzed by using ab initio Hartree-Fock
      static exchange and restricted-active-space self-consistent-field calculations. A
      variety of derivative molecules were calculated to investigate the energetic
      shifts due to environmental effects on the nitrogen atoms. Shake-up excitations
      were also addressed.

PMID- 11512702
TI  - S K- and Mo L-edge X-ray absorption spectroscopy to determine metal-ligand charge
      distribution in molybdenum-sulfur compounds.
AB  - Mo L-edge and S K-edge X-ray absorption spectroscopy were applied to investigate
      the charge distribution between Mo and S in a series of Mo thiolate compounds,
      which serve as amide-sulfur H-bonding models and exhibit different redox
      potentials arising from polar group effects and ligand hydrogen bonds near the
      redox center. For all oxidized complexes, the S K-edge spectra exhibit a thiolate
      based pre-edge feature centered at 2470.2 eV and the inflection point oCCurs at
      2472.0 eV. No intense pre-edge feature is observed in the spectra for the reduced
      Mo model compounds and the energy shift of the S K-edge position depends on the S
      ligand. Correlations between ligand charge density and the redox potential of the
      Mo-S cores are observed.

PMID- 11512703
TI  - Oxygen K-edge X-ray absorption near edge structures (XANES) of sublimated films
      of amino acids.
AB  - Oxygen K-edge X-ray absorption near edge structures (XANES) spectra of amino
      acids (glycine, L-alpha-alanine, beta-alanine, L-serine, L-asparic acid and L
      tyrosine) were measured. Several peaks of XANES spectra were successfully
      assigned on the basis of DV-Xalpha calculation.

PMID- 11512704
TI  - Studies of the magnetic structure at the ferromagnet-antiferromagnet interface.
AB  - Antiferromagnetic layers are a scientifically challenging component in
      magnetoelectronic devices, such as magnetic sensors in hard-disk heads, or
      magnetic random-access memory (RAM) elements. In this paper, it is shown that
      photoelectron emission microscopy (PEEM) is capable of determining the magnetic
      structure at the interface of ferromagnets and antiferromagnets with high spatial
      resolution (down to 20 nm). Dichroism effects at the L edges of the magnetic 3d
      transition metals, using circularly or linearly polarized soft X-rays from a
      synchrotron source, give rise to a magnetic image contrast. Images, acquired with
      the PEEM2 experiment at the Advanced Light Source, show magnetic contrast for
      antiferromagnetic LaFeO3, microscopically resolving the magnetic domain structure
      in an antiferromagnetically ordered thin film for the first time. Magnetic
      coupling between LaFeO3 and an adjacent Co layer results in a complete
      correlation of their magnetic domain structures. From field-dependent
      measurements, a unidirectional anisotropy resulting in a local exchange bias of
      up to 30 Oe in single domains could be deduced. The elemental specificity and the
      quantitative magnetic sensitivity render PEEM a perfect tool to study magnetic
      coupling effects in multilayered thin-film samples.

PMID- 11512705
TI  - Measurements of photon interference X-ray absorption fine structure (piXAFS).
AB  - Experimental data are presented which demonstrate the existence of a fine
      structure in extended X-ray absorption spectra due to interference effects in the
      initial photon state (piXAFS). Interference occurs between the incident
      electromagnetic wave and its coherently scattered waves from neighboring atoms.
      Using fine platinum and tungsten powders as well as polycrystalline platinum
      foil, piXAFS was measured in high-precision absorption experiments at beamline X1
      at HASYLAB/DESY over a wide energy range. piXAFS is observed below and above
      absorption-edge positions in both transmission and total-electron-yield
      detection. Based on experimental data it is shown that piXAFS is sensitive to
      geometric atomic structure. Fourier-transformed piXAFS data carry information,
      comparable with that of EXAFS, about the short-range-order structure of the
      sample. Sharp structures occur in piXAFS when a Bragg backscattering condition of
      the incident X-rays is fulfilled. They allow precise measurement of long-range
      order structural information. Measured data are compared with simulations based
      on piXAFS theory. Although piXAFS structures are similarly observed in two
      detection techniques, the importance of scattering off the sample for the
      measurements needs to be investigated further. Disentangling piXAFS,
      multielectron photoexcitations and atomic XAFS in high-precision measurements
      close to absorption edges poses a challenge for future studies.

PMID- 11512706
TI  - Theory of resonant X-ray emission spectroscopy.
AB  - A short review is presented of recent topics in resonant X-ray emission
      spectroscopy (RXES), especially of the polarization dependence of RXES in d and f
      electron systems. Polarization-dependent RXES provides important information on
      the symmetry of electronic states. A scattering-angle dependence in the
      fluorescence yield of rare-earth metals, RXES in polarized and depolarized
      configurations of TiO2, and the magnetic circular dichroism in RXES of
      ferromagnetic systems are discussed together with typical experimental data.

PMID- 11512707
TI  - Hartree-Fock study of orbital magnetic moments in 3d and 5f magnets and X-ray
      magnetic circular dichroism.
AB  - The spin (Ms) and orbital magnetic moments (Mo) of the uranium 5f state in the
      ferromagnetic compound uranium sulfide (US) and of the cobalt 3d state in various
      transition-metal superlattices are calculated on the basis of a tight-binding
      model, in which the intra-atomic f-f or d-d multipole interaction is taken into
      account using the Hartree-Fock (HF) approximation. The parameters in the model
      are determined on the basis of available first-principles calculations. For US,
      the calculated ratio Mo/Ms and magnetic circular dichroism spectrum for U M4,5
      absorption are in good agreement with the experimental results. Inclusion of the
      expectation values of the spin-off-diagonal operators in addition to the number
      operators in the 5f state is found to be crucially important when describing the
      5f magnetic state. A difference in enhancement of Mo of the Co atom between the
      Co/Pd and Co/Cu superlattices is discussed on the basis of a semi-quantitative
      calculation, assuming ferromagnetism.

PMID- 11512708
TI  - Magnetic X-ray circular dichroism on in situ grown 3d magnetic thin films on
      surfaces.
AB  - Epitaxic thin and ultrathin films on surfaces allow crystallographic phases that
      do not occur naturally in the bulk to be stabilized. They also offer new
      possibilities for an improved understanding of soft X-ray photoabsorption in
      magnetic systems. Data collected using the Elliptically Polarizing Undulator at
      BL 5.2 of the Stanford Synchrotron Radiation Laboratory are presented herein. Fe,
      Co and Ni films were prepared on Cu(100) surfaces. L2,3-edge spectra were
      recorded with circular and linear light. Fresnel diffractometry was used to
      quantify the degree of transverse beam coherence. A quantitative analysis of the
      spectral features indicates a correlation of the spectral intensities and the
      transverse beam coherence. Resonant reflectivity spectra for Co ultrathin films
      that exhibit strong dichroism are presented. The reflectivity data indicate that
      interference effects of the reflected beams at the two interfaces are of
      importance, even for ultrathin films.

PMID- 11512709
TI  - Study of magnetic materials using helicity-modulated X-ray magnetic circular
      dichroism.
AB  - A new helicity-modulation technique has been applied for recording X-ray magnetic
      circular dichroism (XMCD) at the K-absorption edge in transition-metal magnetic
      materials. This technique enables the measurement of the XMCD spectrum with high
      precision and under extreme conditions. The refined spectrum is presented at the
      Fe K edge for pure Fe, Fe4N and Co-ferrite. The method is very promising for site
      assignment of magnetic cations and for detailed investigation of the magnetic
      states in a local environment. In Mn3MC perovskites, the dependence of the Mn K
      edge XMCD spectrum on temperature and magnetic field demonstrates that the
      orbital moments are closely associated with the magnetic phase transition. New
      information obtained from the refined spectrum and novel phenomena observed in
      temperature and field variations is presented.

PMID- 11512710
TI  - Small hydrocarbons on metal surfaces: adsorption-induced changes in electronic
      and geometric structure as seen by X-ray absorption spectroscopy.
AB  - Monolayers of several unsaturated and saturated hydrocarbons (ethylene,
      acetylene, benzene, n-hexane, cyclohexane, n-octane, n-hexatriacontane) adsorbed
      on a number of different metal surfaces [Cu(111), Au(111), Ru(0001) and Pt(111)]
      have been investigated by carbon K-edge X-ray absorption spectroscopy (XAS).
      Whereas the corresponding multilayer data qualitatively resemble the core
      excitation spectra observed for the free molecules, generally significant
      modifications are observed in the monolayer data. For the saturated hydrocarbons,
      a strong quenching of the Rydberg R resonance at 287.7 eV and the appearance of a
      new broad feature at around 285.1 eV (M resonance) is observed for molecules in
      direct contact with the metal surfaces. In the case of the unsaturated
      hydrocarbons, for a number of metals, distinct new features are seen in the XAS
      data, revealing significant intramolecular distortions.

PMID- 11512711
TI  - Electronic structure effects from hydrogen bonding in the liquid phase and in
      chemisorption: an integrated theory and experimental effort.
AB  - A closely integrated theoretical and experimental effort to understand chemical
      bonding using X-ray spectroscopic probes is presented. Theoretical techniques to
      simulate XAS (X-ray absorption spectroscopy), XES (X-ray emission spectroscopy),
      RIXS (resonant inelastic X-ray scattering) and XPS (X-ray photoelectron
      spectroscopy) spectra have been developed and implemented within a density
      functional theory (DFT) framework. In combination with new experimental
      techniques, such as high-resolution XAS on liquid water under ambient conditions
      and XES on complicated surface adsorbates, new insight into e.g. hydrogen-bonded
      systems is obtained. For the (3x2) overlayer structure of glycine/Cu(110),
      earlier work has been extended to include adsorbate-adsorbate interactions.
      Structures are optimized for large cluster models and for periodic boundary
      conditions. It is found that specific features in the spectra arise from hydrogen
      bonding interactions, which thus have important effects at the molecular-orbital
      level. XAS on liquid water shows a pronounced pre-edge feature with significant
      intensity, while the spectrum of ice shows only little intensity in this region.
      Theoretical spectrum calculations, based on instantaneous structures obtained
      from molecular-dynamics (MD) simulations, show that the pre-edge feature in the
      liquid is caused by water molecules with unsaturated hydrogen bonding. Some
      aspects of the theoretical simulations will be briefly discussed.

PMID- 11512712
TI  - Surface EXAFS study of metastable magnetic thin films.
AB  - Epitaxial thin films provide new opportunities to explore the relationship
      between structure and magnetism. The bidimensionnal character of magnetic films
      deposited on single-crystal substrates and the occurrence of singular
      crystallographic structures often confer on these systems electronic and magnetic
      properties that cannot be found in the bulk solids. Although shape anisotropy
      would favour an in-plane easy axis of magnetization for thin films, Ni layers
      deposited on Cu(001) present a perpendicular magnetic anisotropy in a very wide
      thickness range. It is shown that this can be explained by a distorted structure
      of Ni, originating from the strain induced by the epitaxy on the Cu substrate. In
      the field of low-dimensional magnetism, nanostructures with a reduced lateral
      dimension are now being widely investigated in view of their technological
      applications. Thin Fe layers on MgO(001) can be cut into strips by the 'atomic
      saw' method: a compression of the substrate induces a dislocation slipping which
      'saws' both the substrate and the Fe film into regular and separated ribbons. The
      observed magnetic anisotropy, with the easy axis perpendicular to the strips, is
      explained by a structural relaxation occurring during the structuration process.
      In these two studies, a precise structural characterization and simple
      magnetoelastic models allow the magnetic behaviour of the systems to be
      described. The structure of the films can be described as an elastic deformation
      of the bulk structure.

PMID- 11512713
TI  - X-ray absorption studies of carbon-related materials.
AB  - X-ray absorption near-edge structure (XANES) measurements have been performed on
      nitrogen-doped diamond films with three different dopant concentrations and iron
      layer-stabilized carbon nanotube (CNT) structures with various diameters at the C
      K-absorption edge using the sample drain current mode. The C K-edge XANES spectra
      of these N-doped diamond films resemble that of the undoped diamond regardless of
      the dopant concentration, which suggest that the overall bonding configuration of
      the C atom is unaltered. N dopants are found to reduce the intensities of both
      the sp2- and sp3-bond-derived resonance features in the XANES spectra. On the
      other hand, the C K-edge XANES spectra of CNTs indicate that the intensities of
      the pi* and sigma* bands and the interlayer-state features vary with the diameter
      of the CNT. This phenomenon may be caused by the Fe-layer-catalysed bending of
      the graphite sheet and the interaction between C and Fe atoms.

PMID- 11512714
TI  - Theoretical studies of core excitation and ionization in molecular systems.
AB  - Photoionization cross sections have been computed using correlated initial and
      final target states obtained with standard ab initio techniques and using a
      numerical representation of the continuum scattering orbitals. Here, core
      ionization of small molecular systems will be focused on. A brief review of
      previous results obtained using these methods is given. New results are then
      given for the N 1s ionization of NO and the N 1s ionization of N2. In the study
      of NO, the spin-coupling scheme which best describes the shape-resonant state and
      the energy dependence of the branching ratios for the singlet and triplet final
      ion states will be considered. In the study of N2 core ionization. the effects of
      the coupling of nearly degenerate core levels and the effects of correlation on
      the importance of interchannel coupling will be considered.

PMID- 11512715
TI  - Progress on inner-shell excitations of molecular van der Waals clusters.
AB  - Recent progress on core-level excitation of molecular van der Waals clusters is
      reported. Resonant excitation near element K edges of isolated and clustered
      molecules gives rise to small spectral shifts that can only be detected with high
      spectral resolution. This requires the use of state-of-the-art storage-ring
      facilities along with insertion devices and high-resolution soft X-ray
      monochromators. Selected experimental results on carbon monoxide clusters are
      reported. For the vibrationally resolved C 1s --> pi* (v = 0) band of clustered
      CO, these indicate characteristic line broadening as well as a small red shift of
      2 +/- 1 meV compared with the isolated molecule. The results are discussed within
      the framework of the quasi-atomic approach with respect to intermolecular
      interactions, freezing of molecular rotations in clusters, and dynamic
      localization of resonant core-to-valence excitations.

PMID- 11512716
TI  - QEXAFS study of the sulfidation of NiMo/Al2O3 hydrotreating catalysts.
AB  - Quick-scanning extended X-ray absorption fine structure (QEXAFS) spectroscopy was
      employed to investigate in situ the sulfidation of Mo and Ni in y-AI2O3-supported
      hydrotreating catalysts modified with chelating ligands. Mo K-edge QEXAFS enabled
      the detection of an intermediate product in the sulfidation of Mo. The parameters
      obtained from the fits of the QEXAFS spectra showed that this product consists of
      compounds similar to Mo2S2-(12) or Mo3S2-(13). QEXAFS also demonstrated that the
      sulfidation of Ni is strongly influenced by the presence of chelating ligands.
      Classical EXAFS spectra of the sulfided catalysts showed that Ni forms small
      sulfided clusters, the size of which is influenced by the presence or absence of
      the chelating agents.

PMID- 11512717
TI  - Linear combination of XANES for quantitative analysis of Ti-Si binary oxides.
AB  - A new method is demonstrated for the quantification of Ti-O-Si and Ti-O-Ti bonds
      in Ti-Si binary oxides. It is based on the linear combination of two reference X
      ray absorption near-edge structure (XANES) spectra at the Ti K edge. The proper
      selection of a Ti-O-Si reference material is most important for the successful
      application of this method. Three Ti-Si binary oxide systems have been analysed
      by the new method: Ti-Si mixed oxides, titania supported on silica and Ti
      substituted MCM-41 (crystalline mesoporous molecular sieve material invented by
      Mobil) with various Ti contents.

PMID- 11512718
TI  - Development of an in situ polarization-dependent total-reflection fluorescence
      XAFS measurement system.
AB  - An in situ polarization-dependent total-reflection fluorescence X-ray absorption
      fine structure (PTRF-XAFS) spectroscopy system has been developed, which enables
      PTRF-XAFS experiments to be performed in three different orientations at various
      temperatures (273-600 K) and pressures (10(-10) approximately 760 torr). The
      system consists of a measurement chamber and a preparation chamber. The
      measurement chamber has a high-precision six-axis goniometer and a multielement
      solid-state detector. Using a transfer chamber, also operated under ultra-high
      vacuum conditions, the sample can be transferred to the measurement chamber from
      the preparation chamber, which possesses low-energy electron diffraction, Auger
      electron spectroscopy and X-ray photoelectron spectroscopy facilities, as well as
      a sputtering gun and an annealing system. The in situ PTRF-EXAFS for Cu species
      on TiO2 (110) has been measured in three different orientations, revealing
      anisotropic growth of Cu under the influence of the TiO2 (110) surface.

PMID- 11512719
TI  - EXAFS and molecular dynamics studies of ionic solutions.
AB  - This paper focuses on recent advances in the X-ray absorption spectroscopy (XAS)
      analysis of ionic solutions. The asymmetry of radial distribution functions g(r)
      associated with the solvent molecules surrounding the ions has to be taken into
      account to perform a reliable structural analysis. Molecular dynamics (MD)
      simulations provide reliable g(r)'s which can be used as starting models in the
      XAS data analysis. The combined MD-XAS investigation reduces meaningfully the
      indetermination of the structural parameters, especially for coordination numbers
      and Debye-Waller factors. Double-electron excitation channels can be present in
      the XAS spectra of ionic solutions and they have to be accounted for in the
      background extraction. The ability of the XAS technique to probe three-body
      correlation functions in ionic solutions with the aid of MD g(r1, r2, theta) has
      been shown. The analysis of the low-k region of the spectra allows the detection
      of a weak but significant hydrogen structural signal. The XAS technique is
      especially well suited to determine the detailed shape of the nearest-neighbor
      peak in the atom-atom pair correlation functions of disordered systems. The
      information that they contain about the short-range atom-atom pairwise
      interactions can be very helpful for specifying and properly modifying model
      potentials used in MD simulations.

PMID- 11512720
TI  - An X-ray absorption spectroscopy study of the pressure and temperature dependence
      of ZnBr2 aqueous supercritical solutions.
AB  - X-ray absorption spectroscopy (XAS) experiments have been performed on 1.0 and
      1.6 M ZnBr2 aqueous solutions under ambient to supercritical conditions. Both the
      X-ray absorption near-edge structure (XANES) and the extended X-ray absorption
      fine structure (EXAFS) show striking evolutions, which indicate major structural
      changes, with a strong reduction in hydration and the increasing formation of
      ZnBr pairs. A quantitative analysis of the evolution of the Zn environment is
      presented that supports the existence of a transition from an octahedral to a
      tetrahedral environment.

PMID- 11512721
TI  - XAFS study on liquid selenium under high pressure.
AB  - Using large-volume presses, it is now possible to measure X-ray absorption
      spectra under a wide range of pressure-temperature conditions. X-ray absorption
      fine structure (XAFS) has successfully been measured at the K edge of crystalline
      and liquid Se at temperatures up to 1023 K and pressures of about 5 and 8 GPa,
      and at temperatures up to 1173 K at about 2.5 GPa. Crystalline Se consists of
      infinite chain molecules. At atmospheric pressure, it is known that the chain
      structure of Se is largely preserved upon melting. The temperature dependence of
      the extended X-ray absorption fine structure (EXAFS) at 2.5 GPa indicates that
      twofold covalent bonds remain upon melting, as at atmospheric pressure. On the
      other hand, the decrease of EXAFS oscillation upon melting at 8 GPa is larger
      than that expected from the temperature dependence of EXAFS in the crystalline
      state, indicating that the covalent bonds are modified in the liquid state. The
      change of structure of liquid Se is discussed in relation to a proposed
      semiconductor-metal transition under high pressure.

PMID- 11512722
TI  - Dopant structural distortions in high-temperature superconductors: anactive or a
      passive role?
AB  - The parent compounds of high-temperature superconductors, such as YBa2Cu3O6 and
      La2CuO4, are strongly interacting electron systems, rendering them insulators
      with Mott-Hubbard gaps of a few electronvolts. Charge carriers (holes) are
      introduced by chemical doping, causing an insulator-metal (IM) transition and, at
      low temperatures, superconductivity. The role of dopants is widely seen as
      limited to the introduction of holes into the CuO2 planes (i.e. occupying
      electronic states derived from Cu 3d(x2-y2) and O 2p(x,y) atomic orbitals). Most
      theories of high-Tc superconductivity deal with pairing interactions between
      these planar holes. Local distortions around dopants are poorly understood,
      because of the experimental difficulty in obtaining such information,
      particularly at low doping. This has resulted in the neglect, in most theories,
      of the effect of such distortions on the chemical and electronic structure of
      high-Tc superconductors. Angular-resolved X-ray absorption fine structure (XAFS)
      spectroscopy on oriented samples is an ideal technique to elucidate the dopant
      distortions. Element specificity, together with a large orientation dependence of
      the XAFS signal in these layered structures, allows the local structure around
      dopants to be resolved. Results are presented here on (Sr, Ba) and Ni dopants,
      which substitute at the La and Cu sites, respectively, of insulating La2CuO4. The
      relevance of the measured local distortions for a complete understanding of the
      normal and superconducting properties of cuprates is discussed.

PMID- 11512723
TI  - Lattice disorder in strongly correlated lanthanide and actinide intermetallics.
AB  - Lanthanide and actinide intermetallic compounds display a wide range of
      correlated-electron behavior, including ferromagnetism, antiferromagnetism,
      nonmagnetic (Kondo) ground states, and so-called 'non-Fermi liquid' (NFL)
      behavior. The interaction between f electrons and the conduction band is a
      dominant factor in determining the ground state of a given system. However,
      lattice disorder can create a distribution of interactions, generating unusual
      physical properties. These properties may include NFL behavior in many materials.
      In addition, lattice disorder can cause deviations from standard Kondo behavior
      that is less severe than NFL behavior. A review of the lattice disorder mechanism
      within a tight-binding model is presented, along with measurements of the YbBCu4
      and UPd(x)Cu(5-x) systems, demonstrating the applicability of the model. These
      measurements indicate that while the YbBCu4 system appears to be well ordered,
      both site interchange and continuous bond-length disorder occur in the UPd(x)Cu(5
      x) series. Nevertheless, the measured bond-length disorder in UPdCu4 does not
      appear to be enough to explain the NFL properties simply with the Kondo disorder
      model.

PMID- 11512724
TI  - Iron and copper K-edge XAS study of serotransferrin and ovotransferrin.
AB  - The active metal site structure of transferrin with iron and copper atoms is
      investigated using metal K-XANES. Theoretical analysis of experimental data has
      been performed on the basis of full multiple-scattering theory. This approach
      made it possible to study the origin of XANES fine details and to investigate the
      local structure around active metal sites. A deep insight into the local
      structure and electronic subsystem of Fe, Cu transferrins is obtained. For
      example, in the case of Cu substitution of Fe in the active centre, the best fit
      of theoretical spectra to experiment has been obtained for distances 3% smaller
      between the Cu atom and the nearest neighbours.

PMID- 11512726
TI  - Theory of photon interference X-ray absorption fine structure.
AB  - The theory of photon interference x-ray absorption fine structure (piXAFS) is
      described. Due to coherent x-ray scattering from atoms, a spatial variation of
      the x-ray intensity is produced inside the sample. The intensity at the x-ray
      absorbing atom changes according to the incident energy. Thus piXAFS in extended
      absorption spectra is produced. It extends in a wide energy range over absorption
      edges. For powders the piXAFS formula has equivalent form as the EXAFS formula,
      and the Fourier transform provides distances of neighboring atoms from the
      absorbing atom. Due to a long mean free path of the photon, piXAFS for powders
      contains sharp structures. They are explained as a crystal grain orientation
      averaging of the x-ray standing wave effect.

PMID- 11512727
TI  - Theoretical study of the non-local optical potential in EXAFS spectra.
AB  - We study the optical potential effects on the extended x-ray absorption fine
      structure (EXAFS) and x-ray photoelectron diffraction (XPD) spectra. For the
      valence electron optical potential we use a local density approximation because
      the charge density changes fairly slowly, whereas we use a non-local optical
      potential for the core electron part based on GW-approximation. In the Br K-edge
      EXAFS spectra the present optical potential gives rise to the phase difference
      and the amplitude reduction; the agreement with the experimental result is
      excellent. In the N-1s XPD spectra for N2/Ni(100), the spherical wave effects
      enhance the effects due to the optical potential.

PMID- 11512725
TI  - High-resolution X-ray spectroscopy of rare events: a different look at local
      structure and chemistry.
AB  - The combination of large-acceptance high-resolution X-ray optics with bright
      synchrotron sources permits quantitative analysis of rare events such as X-ray
      fluorescence from very dilute systems, weak fluorescence transitions or X-ray
      Raman scattering. Transition-metal Kbeta fluorescence contains information about
      spin and oxidation state; examples of the characterization of the Mn oxidation
      states in the oxygen-evolving complex of photosystem II and Mn-consuming spores
      from the marine bacillus SG- are presented. Weaker features of the Kbeta spectrum
      resulting from valence-level and 'interatomic' ligand to metal transitions
      contain detailed information on the ligand- atom type, distance and orientation.
      Applications of this spectral region to characterize the local structure of model
      compounds are presented. X-ray Raman scattering (XRS) is an extremely rare event,
      but also represents a unique technique to obtain bulk-sensitive low-energy (<600
      eV) X-ray absorption fine structure (XAFS) spectra using hard (approximately 10
      keV) X-rays. A photon is inelastically scattered, losing part of its energy to
      promote an electron into an unoccupied level. In many cases, the cross section is
      proportional to that of the corresponding absorption process yielding the same X
      ray absorption near-edge structure (XANES) and extended X-ray absorption fine
      structure (EXAFS) features. XRS finds application for systems that defy XAFS
      analysis at low energies, e.g. liquids or highly concentrated complex systems,
      reactive compounds and samples under extreme conditions (pressure, temperature).
      Recent results are discussed.

PMID- 11512728
TI  - Theory of spin-polarized optical potential.
AB  - We develop an approximation for the non-local spin-polarized optical potential
      theory for atoms in solids at intermediate and high energy. The present
      approximation for the optical potential builds on the GW-expression. We separate
      the RPA polarization propagator into a core electron and a valence electron part,
      and can then achieve a corresponding separation of the optical potential. For the
      valence electron optical potential we use a local density approximation because
      the charge density changes fairly slowly, whereas we use a non-local optical
      potential for the core electron part. Both of them depend on the spin
      polarization. We apply this method to electron-Fe elastic scattering in solid,
      and discuss the results.

PMID- 11512729
TI  - Double-channel excitation in the XAS spectra of divalent and trivalent iron
      complexes in water solution.
AB  - We present a detailed analysis of XAS spectra of divalent and trivalent iron
      complexes in water solutions. The interpretation of the spectra has been provided
      by multi-channel multiple scattering approach. On this basis, good agreement
      between experimental data and theoretical calculations has been obtained in both
      cases including two excitation channels in the final state.

PMID- 11512730
TI  - Symmetry role on the preedge X-ray absorption fine structure at the metal K edge.
AB  - The preedge features in a system with "even" symmetry, apart from quadrupolar
      transition contribution, are mainly dipolar in character, associated with the
      existence of unoccupied states made up of mixed cation-4p with higher-neighboring
      cation-3d orbitals, and reflect the density of states due to the medium-range
      order of the system. In "odd" symmetry materials these preedge features are the
      result of a transition from the 1s to a final density of states of p symmetry due
      to an unsymmetrical mixing of the ligand wave functions with the central cation
      3d orbitals, similar to atetrahedral configuration. These results are validated
      for Fe as a photoabsorber by comparing XAS spectra of Fe2SiO4 (fayalite) to ab
      initio full multiple scattering calculations at the Fe K edge, but pertain to all
      systems containing sixfold-coordinated cations.

PMID- 11512731
TI  - Yields of multiply charged ions in cascading decays of hollow argon and krypton
      with two initial vacancies in their K and/or L shells.
AB  - The yields of multiply charged ions produced by the cascading decay of doubly
      inner-shell-ionized argon and krypton atoms are calculated via straightforward
      construction of de-excitation trees. The final-ion-charge spectra are found to be
      sensitive to the distribution of initial vacancies within K and L shells.

PMID- 11512732
TI  - Calculation of rare-earth 4d giant-absorption spectra with multiplet effects and
      decay processes.
AB  - The total and partial photoelectron yield spectra of all the trivalent rare-earth
      ions in the 4d giant resonance region are calculated with full multiplet effects.
      The decay processes are treated as coherent processes following photoexcitation.
      The results reproduce the over all features of experiments. It is obtained that
      the character of the giant-absorption is different between the light and heavy
      rare-earths. The multiplet effects play an essential role in the decay processes.

PMID- 11512733
TI  - Towards a limited XANES refinement in strongly correlated systems.
AB  - Three components of O1 atom displacements have been derived from the direct fit
      of the polarized Ellab Cu K-edge XANES spectrum of Nd(1.85)Ce(0.15)CUO(4-delta)
      superconductor. The best fit is achieved for a 60 to 40% mixture of 2x2
      undistorted antiferromagnetic and modified charge density wave (MCDW) domains.
      The local structure of the MSDW is characterized by correlated displacements of
      deltaO1 parallel = 0.12 +/- 0.04, deltaO1 perpendicular = 0.25 +/- 0.08, and
      deltaO1z = 0.12 +/- 0.1 A. An agreement factor over the range of 8980-9040 eV is
      2-3 times smaller than it may be obtained from single-electron MS calculations.
      This improvement comes from accounting for many-body excitations and the
      relationship between electronic and local structure in the CuO2 planes.

PMID- 11512734
TI  - Quantum statistical approach to Debye-Waller factor in EXAFS: application to
      monatomic fcc systems.
AB  - Temperature dependence of the Debye-Waller factors in EXAFS is studied for
      monatomic fcc lattice by use of the perturbation approach in terms of temperature
      Green's function. We apply the theory to the temperature dependence of EXAFS for
      Kr and Ni crystals. Furthermore we make a comparison among sc, bcc and fcc
      lattices for the present ab initio calculations.

PMID- 11512735
TI  - Observation of anharmonicity for copper thin film near room temperatures.
AB  - The fluorescence EXAFS spectra for a copper thin film with a thickness of 3000A
      measured at 300K, 350K and 400K were analyzed by the regularization method to
      directly obtain the radial distribution. The pair distribution was almost
      symmetric for 300K but asymmetric for 350K and 400K. This indicates that the
      atoms in copper vibrate anharmonically near room temperatures. The anharmonicity
      and the skewness of the asymmetric distribu-tion increases as temperature
      increases.

PMID- 11512736
TI  - Probability density of wave function of excited photoelectron: understanding
      XANES features.
AB  - Interpretation of XANES spectra suffers from a poor intuitive understanding of
      the relation between spectral features and structural elements of a material. An
      attempt to alleviate this shortcoming is made by exploring a spatial distribution
      of probability density of wave functions of photoelectrons excited during the
      photoabsorption process. One has to add incoherently squares of wave functions
      which describe participating photoelectron diffraction (PED) processes, weighted
      by normalized PED cross sections. As an example, we investigate probability
      density of wave functions relevant to Ag L1 and L3 XANES of Ag2O.

PMID- 11512737
TI  - Polarized Cu K edge XANES spectra of CuO--theory and experiment.
AB  - Polarized Cu K edge x-ray absorption near-edge structure (XANES) spectra of CuO
      are analyzed. Partial spectral components reflecting both dipole and quadrupole
      transitions are resolved from the experiment. Theoretical spectra were obtained
      using the real-space multiple-scattering technique and by calculating the band
      structure via the pseudopotential method. We demonstrate that the pre-peak is of
      a quadrupole character and find its decomposition into individual d components.
      The self consistent pseudopotential calculation, free from any constraints on the
      form of the potential, improves the agreement between theory and experiment in
      those areas where real-space calculation, based on non-self-consistent muffin-tin
      potential, fails. Therefore we argue that the most significant contributions to
      the Cu K edge XANES come from one-electron processes.

PMID- 11512738
TI  - Electronic structure investigation of Mg(1-x)Fe(x)S solid solution: X-ray
      absorption study.
AB  - X-ray absorption fine structure at the sulfur K edge in Mg(1-x)Fe(x)S solid
      solution (0 < or = x < or = 0.68) has been measured at the Canadian Synchrotron
      Radiation Facility. It was shown that the S K-edge in MgS was formed by the
      multiple scattering of the photoelectron wave within a cluster of large size
      (containing 27 atoms and having radius about 4.5 A). Comparison of experimental
      data with theoretical results allows study of the electronic structure of this
      system. The analysis of partial electronic density of s-, p- and d- states makes
      it possible to investigate the mutual influence of sulfur s-, p- and metal d-
      states in the conduction band. The study of changes in experimental S K-edges
      XANES of Mg(1-x)Fe(x)S solid solution with variation of relative Fe-Mg
      concentration allows the extraction of the hypothetical cubic phase (B1) of FeS,
      and this is supported by theoretical simulation.

PMID- 11512739
TI  - Orientation effects in elastic scattering of polarized X-rays by linear
      molecules.
AB  - Strong orientation effect is discovered theoretically upon the change of the
      scheme of suggested experiment on anomalous elastic x-ray scattering of linearly
      polarized x-ray radiation by linear diatomics near the ionization thresholds of
      inner molecular orbitals. Studied are the effects on the shape of theoretical
      scattering spectra of additional excitations/ionizations of outer-shell
      electrons. Within the one-centre approximation for the molecular orbitals
      wavefunctions the analytical structure of the linear molecule's formfactor is
      obtained. The dipole transition matrix elements and photoabsorption cross
      sections are calculated by the methods of the theory of non-orthogonal orbitals.

PMID- 11512740
TI  - Theory of oxygen 1s resonant X-ray emission spectroscopy in copper-based oxides.
AB  - Many-body effects on the oxygen 1s resonant x-ray emission spectrum (O 1s RXES)
      in copper-based oxides, such as Sr2CuO3 and La2CuO4, are discussed on the basis
      of cluster-model calculations. The Zhang-Rice singlet excitation, which is a
      typical many-body state in Cu-based oxide systems, can be detected at low
      temperatures where the antiferromagnetic correlation between the neighboring Cu
      spins is strong. Thus the present study emphasizes that the O 1s RXES can be a
      good tool to obtain information on the Cu 3d states. In particular the
      polarization-dependent RXES gives the symmetry-decomposed information.

PMID- 11512741
TI  - Multiple ionization upon K-shell photoabsorption of the CO and N2 molecules.
AB  - The spectra of multiple ionization of CO and N2 in the gas phase in the region of
      the K-shell ionization thresholds of C and N are studied theoretically. The
      processes of additional excitation/ionization from 1pi and 5sigma-shells are
      included. The effects of many-electron correlations on the extention of multiplet
      structure for some configurations of multiple excitations is studied. Absolute
      values of photoabsorption cross sections are calculated in some of the channels
      of multiple ionization.

PMID- 11512742
TI  - Double electron transitions [MN] or [MO] above 74W MIII edge in X-ray absorption
      spectra.
AB  - The x-ray absorption spectra in metallic W (Tungsten) have been measured above
      MIII edge using the third generation synchrotron radiation. ALS, Berkeley.
      Several features caused by multi-electron transitions were detected on MIII in
      solid phase. [3p4f], [3p5s], and [3p5p] double electron transitions were
      identified by the Z+1 approximation.

PMID- 11512743
TI  - The role of the electron inelastic scattering processes in EELFS spectra.
AB  - The pseudopotential model is used for the evaluation of the core level ionisation
      intensities (by the electron impact). The central atom effective phase shift is
      calculated for K EELFS spectra in this framework. The Si K EELFS spectra were
      calculated and compared with the experimental data. The comparison of
      experimental and calculated results is performed on the base of the electron
      dispersion law which takes into account electron-plasmon interaction.

PMID- 11512744
TI  - Calcium L-edge XANES study of some calcium compounds.
AB  - The Ca L3,2-edge XANES spectra of six calcium salts have been measured in both
      total electron and fluorescence yields using a high-resolution spherical grating
      monochromator. The compounds investigated were; CaF2, CaCO3, CaCl2 x 2H2O,
      calcium phosphate, calcium glycerophosphate and calcium gluconate. We find that
      the fine structure of the Ca L3,2-edges for each compound is unique and relates
      to the local structure of the Ca atom. The implications of these results to the
      study of the structure of calcium binding sites in systems of biologically
      interest will be discussed.

PMID- 11512745
TI  - Verification of a distortion in the microstructure of GaN detected by EXAFS using
      ab initio density functional theory calculations.
AB  - X-ray absorption fine structure (XAFS) measurements on a series of epitaxially
      grown GaN samples have shown a distortion in the microstructure of GaN. More
      specifically the central N atom is 4-fold coordinated but the four Ga atoms are
      not equidistant. It has been shown that 2.9 to 3.5 of them (depending on the
      growth conditions) are found in the expected from XRD distance of 1.94 A and the
      remaining are at a distance longer by approximately 15%. Second derivative
      calculation of the conformation energy using the Density Functional Theory (DFT)
      is used to investigate if the symmetric GaN cluster as given by XRD is the most
      energetically favorable configuration and if not which distorted structure
      corresponds to the most energetically favorable one. A very good agreement
      between DFT results and experimental XAFS spectra has been found. Generalization
      this technique to other dislocated clusters is also discussed.

PMID- 11512746
TI  - The influence of experimental and model uncertainties on EXAFS results.
AB  - We analyze EXAFS oscillations in k-space with the FEFF code to obtain main-shell
      distances Rv and mean-square displacement parameters sigma2i for all single and
      multiple scattering paths i in the shells v up to a maximum shell radius Rmax. To
      quantify the uncertainty in the determination of these model parameters we take
      into account experimental errors and uncertainties connected with background
      subtraction, with the approximate handling of the electronic many-body problem in
      FEFF, and with the truncation of the multiple scattering series. The impact of
      these uncertainties on the Rv and sigma2i is investigated in the framework of
      Bayesian methods. We introduce an a priori guess of these model parameters and
      consider two alternative strategies to control the weight of the a priori input
      relative to that of the experimental data. We can take a model parameter space of
      up to 250 dimensions. Optionally we can also fit the coordination numbers Nj (j <
      or = v) and the skewness of the distribution of the Rv besides the Rv and
      sigma2i. The method is applied to 10K Cu K-edge and 300K Au L3-edge data to
      obtain model parameters and their a posteriori error correlation matrices.

PMID- 11512747
TI  - A new model for statistical error analysis in XAS: about the distribution
      function of the absorption coefficient.
AB  - Under some general hypothesis, this paper proposes a theoretical model, showing
      that a gaussian distribution is generally a good approximation of the
      experimental distribution of the absorption coefficient. This result is confirmed
      experimentally by usage of appropriate statistical tests.

PMID- 11512748
TI  - MXAN: a new software procedure to perform geometrical fitting of experimental
      XANES spectra.
AB  - A new software procedure, MXAN, to fit experimental XANES spectra is presented
      here. The method is based on the comparison between the experimental spectrum and
      several theoretical calculations generated by changing the relevant geometrical
      parameter of the site around the absorbing atom. The x-ray photoabsorption cross
      section is calculated using the general multiple-scattering scheme, utilizing a
      complex Hedin-Lunqvist energy-dependent potential to describe the exchange
      correlation interaction. Our method has been applied to the study of geometrical
      environment of the tetrahedral zinc site of the protein superoxide dismutase
      (SOD). The experimental Zn K-edge XANES spectrum has been fitted in the space of
      the first shell coordination parameters (ligand distances and angles) following
      the behavior of the chi-square as a function of the local distortion from the
      starting crystallographic structure. The recovered structure is found to be
      independent on the starting conditions, showing the theoretical uniqueness of the
      structural solution. Strengths and limitations of the application to real systems
      are also discussed.

PMID- 11512749
TI  - Statistical evaluations in fitting problems.
AB  - The problem of error analysis is considered taking into account all possible
      correlations and a prior information about the accessible parameter space.
      Special attention is paid to the correct determination of the relative weight of
      experimental data and the a priori guess. The applications of statistical chi2-
      and F-tests to the fitting problems are also discussed.

PMID- 11512750
TI  - Local structure probes of nanoscale heterogeneity in crystalline materials.
AB  - In the conventional model of condensed matter increasing numbers of defects break
      down the order and ultimately convert perfect periodic crystals into aperiodic
      glasses. Local structure probes of a variety of materials with non-stoichiometric
      compositions, multiple degenerate ordering modes, or other symmetry breaking
      factors identify multiple ordered arrangements of atoms that render the materials
      heterogeneous on the nanometer scale. While exerting apparently negligible
      effects on bulk properties, this heterogeneity or phase separation does influence
      correlated or collective properties such as magnetism and phase stability.

PMID- 11512751
TI  - The use of prior information for extracting the post-edge background.
AB  - A new method for extracting the post-edge background mu0 is proposed, the method
      of Bayesian smoothing. A further evolution of the smoothing spline method is
      considered as well. Both techniques are capable to take into account prior
      information about the peculiarities on the mu0. In addition, since the Bayesian
      approach works in terms of the posterior probability density functions, it
      contains a natural way to determine the errors of the mu0 construction, which has
      always been an unresolvable problem for any other method. Even with use of the
      prior information, which narrows the posterior probabilities, the errors of mu0
      are shown to be larger than the experimental noise.

PMID- 11512752
TI  - Atomic background and EXAFS of gaseous hydrides of Ge, As, Se and Br.
AB  - K edge absorption spectra of elements from Ge to Br in gaseous hydrides were
      measured at the BM 29 station of ESRF with noise level as low as 2x10(-5), so far
      achievable only on noble gases. The dominant feature of the spectra is the atomic
      background similar to that of Kr and comparable to it in the quality of detail.
      Onto the background, a smooth weak EXAFS signal due to the hydrogen neighbors is
      superposed. For the very simple molecules such as these, its contribution can be
      calculated ab initio, with exact treatment of the effect of molecular vibrations,
      so that no best-fit adjustment to the experimental data is necessary. In
      comparison to the main constituent of the atomic background, i.e. the shake-up
      absorption edges, the EXAFS signal is of minor importance in HBr with a single H
      neighbor, but of the same order of magnitude in GeH4.

PMID- 11512753
TI  - A study of transferability of atomic background on EXAFS spectra of simple
      gaseous compounds of As.
AB  - From EXAFS spectra of As and As2O3 vapors and arsine gas AsH3 the ab initio
      calculated structural signal is removed. The remainders comprise small absorption
      edges due to shake-up channels involving electrons from 3d or 3p subshell. With
      enhanced resolution, the edges reveal a fine splitting and a varying contribution
      of resonance channels, due to individual molecular energy-level structure of the
      samples. On the resolution level appropriate for routine EXAFS analysis the
      remainders coincide, representing a unique and transferable atomic absorption
      background for the range of As valence states spanned by the samples.

PMID- 11512754
TI  - Determination of parameters of valence states by using XANES.
AB  - A new approach for the parametrization of valence states of atoms in molecules
      and solids, facilitating the deciphering of experimental XANES spectra, is
      proposed. It is shown that energies and half-widths of XANES maxima of the one
      electron origin depend mainly on the arrangement of atoms and energies and mean
      radii of atomic valence states. Just these quantities having distinct physical
      meaning must be determined above all from experiment. A procedure for such a
      determination is developed. Values of energies and mean radii of the nitrogen and
      oxygen atoms in some molecules are obtained.

PMID- 11512755
TI  - The use of the FEFF8 code to calculate the XANES and electron density of states
      of some sulfides.
AB  - The FEFF8 was used to calculate x-ray absorption spectra (XANES) and the local
      partial electron density of states (LDOS) for several sulfides: InPS4 (twice
      defective chalcopyrite), CdIn2S4 (normal spinel) and Tl3AsS3 (space group R3m).
      The calculated XANES are compared with experimental spectra. The self-consistent
      MT-potentials found for clusters of about 35 atoms were used to calculate XANES
      and LDOS for clusters of 87 atoms in the approach of full multiple scattering. In
      all cases the agreement of the simulated XANES and experimental ones is quite
      good. The theoretical LDOS agree well with the experimental x-ray emission K- and
      L2,3-spectra.

PMID- 11512756
TI  - Thickness inhomogeneity and fluorescence effects in EXAFS spectroscopy for powder
      samples: solution of the inverse problem.
AB  - For thin powder samples EXAFS spectra are often suffered from thickness
      inhomogeneity and for thick samples from fluorescence at energies above edge
      absorption. As a result EXAFS amplitude is decreased and information about the
      coordination numbers is distorted. For correction of x-ray absorption spectra on
      inhomogeneity and fluorescence effects we propose a new method of solving an
      inverse problem. Model calculations are carried out. This method is applied to
      preliminary processing EXAFS spectra for Ni-Mn alloys.

PMID- 11512757
TI  - EXAFS spectra above Pb and Pt K edges observed at low temperature.
AB  - X-ray absorption spectra near K edges of Pb (88.0keV) and Pt (78.4keV) for the
      foils were measured in transmission mode at SPring-8. We succeeded for the first
      time in observing the EXAFS oscillation of the Pb foil at 12K, although it was
      failed at room temperature in a previous experiment. The amplitude of the EXAFS
      oscillation of the Pt foil at 12K considerably increased in comparison with that
      at room temperature, indicating that the amplitude is very sensitive to the Debye
      Waller factor at high-k values.

PMID- 11512758
TI  - Chemical transferability of single- and multiple-scattering EXAFS Debye-Waller
      factors.
AB  - Single- and multiple-scattering EXAFS Debye-Waller factors are amplitude
      reduction parameters that appear in the EXAFS chi(k) equation accounting for the
      structural and thermal disorder of a given sample. These parameters must be known
      accurately in order to obtain quantitative agreement between theory and
      experiment. Since experimental data can only support a limited number of fitted
      parameters these factors must be known from another source. Although various
      approaches have been considered in the past with a variety of results, the self
      consistent ab initio Density functional theory stands for the most accurate and
      reliable method regardless of molecular symmetry or other specific sample
      requirements. Since DFT scales as N3 where N is the number of atomic basis set,
      an ab initio calculation on a large structure is not feasible due to enormous CPU
      demand and in many cases due to hard energy/geometry convergence. In this paper
      we present two ways of overcoming this problem. Both they use the idea that by
      reducing the structure, the DWFs are still chemically transferable. In order to
      test this we use the Zn tetraimidazole. This molecule represents typical
      metalorganic ring samples that can be seen in active sites of metaloproteins.
      Results are compared to experimental EXAFS spectra.

PMID- 11512759
TI  - Determination of the local structure of the first and second shells in ordered
      and disordered Ni-Mn alloys.
AB  - The coordination numbers and the interatomic distances for 50, 75 and 80 at.% Ni
      Mn alloys in ordered and disordered states are presented. A new method for
      determining the first and second nearest neighbor coordination numbers in a
      binary alloy is applied. It is shown that magnetic properties of these alloys
      depend on short range order in atomic arrangement.

PMID- 11512760
TI  - Deglitching procedure for XAFS.
AB  - A computer program for eliminating artifacts such as glitches and Bragg peaks of
      the polarized XAFS spectra is presented. It permits to easily locate and to
      eliminate from the EXAFS spectra the additional signals originated from the Bragg
      scattering by crystalline samples. The test of the procedure on the spectra with
      specially introduced artifacts and on the experimental polarized XAFS spectra
      showed its high effectiveness.

PMID- 11512761
TI  - Applications of combined EXAFS and powder diffraction analysis in solid state
      chemistry.
AB  - Recent applications of combined EXAFS/powder neutron and X-diffraction analysis
      are reviewed and provisional results for three additional compounds are
      presented. Criteria for successful refinements are suggested. The new results
      relate to the materials: CoAl2O4, La(6.4)Ca(1.6)Cu6Ni2O20 and
      Pr(0.5)Sr(0.5)FeO(2.75).

PMID- 11512762
TI  - The temperature dependence for the third shell's Fourier-peak of Nb-EXAFS in
      KNbO3 as additional source of information on the local atomic structure.
AB  - The information on the structure of tetragonal KNbO3 is extracted from the
      temperature dependence of the third shell's Fourier-peak of Nb-EXAFS. It is shown
      that this dependence can be explained by two effects: 1) rigid rotations of the
      O6-octahedron and 2) increase of the third shell's DW-parameter. However,
      diffraction data on the temperature dependence of the DW-parameter permit us to
      conclude that the last effect only is sufficient and the O6-octahedron rotation
      doesn't occur in the high-temperature phases of KNbO3. Using EXAFS it is revealed
      that in the neighboring cells Nb-atoms are parallel shifted closely to [211]
      direction in tetragonal phase.

PMID- 11512763
TI  - Determining crystalline atomic positions using XAFS, a new addition to the UWXAFS
      analysis package.
AB  - XAFS and x-ray diffraction (XRD) are complementary structure determination
      techniques. The combination of XAFS and XRD can be used to determine the complete
      crystal structure when diffraction can not be refined. This is often the case at
      high pressures or high temperatures where there is limited access to the samples
      and energy dispersive x-ray diffraction is used. A new method to determine the
      atomic positions within the unit cell using EXAFS data with the programs RUNFIT
      and MKFIT is described. These programs systematically produce and test models for
      the XAFS data that are consistent with the diffraction results. The programs were
      written to solve the structure of two intermediate high pressure phases of AgCl,
      and are distributed with a working example.

PMID- 11512764
TI  - ATOMS: crystallography for the X-ray absorption spectroscopist.
AB  - ATOMS is a user application providing crystallographic functionality useful to x
      ray absorption spectroscopists. ATOMS is also a set of reusable, object-oriented
      software modules written in the Perl programming language providing
      crystallographic functionality and access to databases of absorption coefficients
      and anomalous scattering factors. The main use of the ATOMS program is to
      generate input data for the ab initio, multiple scattering, x-ray absorption
      spectroscopy code FEFF. However the code offers many additional features,
      including useful calculations involving absorption coefficients and simulations
      of Diffraction Anomalous Fine-Structure (DAFS) spectra. Command line, graphical,
      and web-based interfaces to the code are offered as part of the standard
      distribution. As Perl runs on a wide variety of common computer platforms, ATOMS
      itself is a cross platform application. All text presented to the user can be
      internationalized - support for four languages is currently included in the
      package. Development of ATOMS is active - a FEFF interface, structure
      visualization, and additional crystallographic calculations are among the future
      developments.

PMID- 11512765
TI  - APEX version 2.0: latest version of the cross-platform analysis program for
      EXAFS.
AB  - This report describes recent progress on APEX, a free, open source, cross
      platform set of EXAFS data analysis software. In a previous report we described
      APEX 1.0 (Dimakis, N. and Bunker, G., 1999), a free and open source code suite of
      basic X-Ray Absorption Fine Structure (XAFS) data analysis programs for classical
      data reduction and single scattering analysis. The first version of APEX was the
      only cross platform (linux/irix/windows/MacOS) EXAFS analysis program to our
      knowledge, but it lacked important features like multiple scattering fitting,
      generic format conversion from ASCII to University of Washington (UW) binary-type
      files, and user friendly interactive graphics. In the enhanced version described
      here we have added cross-platform interactive graphics based on the BLT package,
      which is an extension to TCL/TK. Some of the utilities have been rewritten in
      native TCL/TK, allowing for faster and more integrated functionality with the
      main package. The package also has been ported to SunOS. APEX 2.0 in its current
      form is suitable for routine data analysis and training. Addition of more
      advanced methods of data analysis are planned.

PMID- 11512766
TI  - Software based digital signal processing and spectrum deconvolution in X-ray
      spectroscopy.
AB  - Approaches for software based digital signal processing and numerical
      deconvolution of measured signals which overcome limitations of state-of-the-art
      systems are described. The basic technical equipment for digital signal
      processing consists of an energy resolving detector with a preamplifier followed
      by a fast sampling analogue-to-digital converter (ADC). The main idea is the
      numerical decomposition of the measured signal into contributions caused by
      single photon absorption using standard pulses. The latter can be obtained by
      measurements under definite conditions. The maximum pulse rate is then limited
      only by the ratio of sampling time to the time between two pulses which should be
      attributed to single events. Thus pulse overlaps do not require pulse rejection.
      At sampling rates of 10(8) samples per second theoretically a comparable photon
      rate can be detected at throughputs of 100%. Beyond that it is outlined that in a
      comparable manner a numerical deconvolution of measured energy spectra (statistic
      distribution functions of single events) into combinations of standard spectra,
      which can likewise be determined by measurement, offers outstanding
      possibilities, too. On the one hand the energy resolution attainable for
      individual events for a given detector can be improved drastically by the
      statistical treatment of spectra. On the other hand an energy resolving work
      principle becomes possible for certain detectors, which do not permit this
      conventionally due to their poor signal to noise ratio.

PMID- 11512767
TI  - IFEFFIT: interactive XAFS analysis and FEFF fitting.
AB  - IFEFFIT, an interactive program and scriptable library of XAFS algorithms is
      presented. The core algorithms of AUTOBK and FEFFIT have been combined with
      general data manipulation and interactive graphics into a single package. IFEFFIT
      comes with a command-line program that can be run either interactively or in
      batch-mode. It also provides a library of functions that can be used easily from
      C or Fortran, as well as high level scripting languages such as Tcl, Perl and
      Python. Using this library, a Graphical User Interface for rapid 'online' data
      analysis is demonstrated. IFEFFIT is freely available with an Open Source
      license. Outside use, development, and contributions are encouraged.

PMID- 11512768
TI  - Magnetic domains in nanostructured media studied with M-TXM.
AB  - Combining X-ray magnetic circular dichroism (X-MCD) with a transmission X-ray
      microscope (TXM) allows to image element-specifically magnetic domain structures
      with 25nm lateral resolution. Both in-plane and out-of-plane systems can be
      studied in applied magnetic fields. Thus field-dependent parameters, as
      individual nucleation fields in magnetic nanostructures can be deduced and
      related to morphology. Images of thermomagnetically written bits in magneto
      optical TbFeCo media proof the reliability of the writing process and the
      importance of an exact thermal design of the systems. Domains observed at
      corresponding Co L edges proof the chemical sensitivity of M-TXM and its
      potential to image few monolayer systems.

PMID- 11512769
TI  - Generation of an X-ray microbeam for spectromicroscopy at SPring-8 BL39XU.
AB  - A pair of elliptical mirrors (KB mirror) was designed and fabricated to realize
      an energy tunable x-ray microbeam for spectromicroscopy at SPring-8 BL39XU. As is
      commonly recognized, the obtainable beam size with the aspherical total
      reflection mirrors is strongly affected with the slope error of the mirror.
      Considering that the extremely high brilliance of the undulator radiation from
      the SPring-8, the small mirror size and the small mirror-to-focus distance were
      employed to minimize effects of the slope error. Preliminary evaluation of the KB
      mirror was carried out using 10 keV monochromatized undulator radiation.
      Alignment of the mirror was assisted by the beam monitor system composed of a
      scintillator and a CCD, and the beam size less than 5 microm can be easily
      achieved even when the source was fully used. The beam size obtained with this
      experiment was 2 x 4 microm2 with the photon flux of 1 x 10(10) photons/s.
      Smaller beam size may be expected with the use of intermediate slits.
      Characterization of trace elements with the spatial resolution will be carried
      out by using x-ray fluorescence (XRF) analysis and x-ray absorption fine
      structure (XAFS) measurements with XRF yield method.

PMID- 11512770
TI  - Capacitance XAFS method: X-ray absorption spectroscopy of low-dimensional
      structures.
AB  - For local structure analyses of low-dimensional structures in semiconductors,
      such as defects, interfaces and surfaces, a new site-selective x-ray absorption
      fine structure (XAFS) measurement, 'capacitance XAFS method', is presented. This
      method measures the x-ray photon energy dependence of the capacitance involved in
      diode structures. Since the capacitance is changed by an x-ray induced
      photoemission of localized electrons in the low dimensional structures, a site
      selective analysis can be made. Although macroscopic x-ray absorption can be
      measured by conventional XAFS analyses, low-dimensional x-ray absorption
      coefficients are observed by the capacitance XAFS measurements.

PMID- 11512771
TI  - New method of the chemical state imaging by EPMA-EXEFS.
AB  - A novel two dimensional imaging technique of the chemical bonding state was
      developed by combining the extended X-ray emission fine structure method with an
      electron probe X-ray microanalyzer mapping technology. With this method, chemical
      state images of some aluminum standard samples were obtained. It was confirmed
      that the obtained images provide correct information of chemical states.

PMID- 11512772
TI  - Extension of a tuned log spiral of revolution fluorescence XAFS detector,
      designed for optimal detection of a particular element Z, to XAFS of elements
      other than Z.
AB  - Recently, it has been demonstrated that an x-ray detector in the form of a log
      spiral of revolution, covered with highly oriented pyrolytic graphite, is an
      excellent device for obtaining the fluorescence XAFS of an element of interest in
      the presence of competing fluorescence from other elements. In the present work
      we investigate the capabilities of a log spiral of revolution (LSR) detector,
      with a geometry optimized for one element (in this case Cr), if used for XAFS of
      other elements.

PMID- 11512773
TI  - High-resolution soft X-ray absorption spectroscopy of solids.
AB  - The present research deals with the high-resolution soft x-ray absorption spectra
      (XAS) of Si, Ce- and Sm- compounds measured at BL25SU of SPring-8. The spectra
      are compared with theoretical results. The Si 1s spectrum shows good agreement
      with the calculated empty density of states so far reported. The Ce 3d spectra
      are very sensitive to the local electronic structure. The Sm 3d XAS of SmS shows
      clear temperature dependence, which is partly explained by a calculation for Sm2+
      ion.

PMID- 11512774
TI  - XAFS at the Pacific Northwest Consortium-Collaborative Access Team undulator
      beamline.
AB  - The Pacific Northwest Consortium-Collaborative Access Team (PNC-CAT) has begun
      operating an insertion device beamline at the Advanced Photon Source. The
      beamline has been extensively used for XAFS studies. This paper summarizes its
      capabilities, and our initial operational experience. The beamline is based on
      APS undulator A, and incorporates full undulator scanning. The monochromator is
      liquid nitrogen cooled and has both Si(111) and Si(311) crystals in a side-by
      side configuration. Crystal changes only take a few minutes. The crystals cover
      the energy range from 3-50 keV with fluxes as high as 2x10(13) ph/sec. Microbeams
      can be produced using Kirkpatrick-Baez mirrors (spot size 1-3 microm) or tapered
      capillaries (sub-microm spots). When these optics are combined with a 13-element
      Ge detector, the beamline provides powerful microbeam imaging and spectroscopy
      capabilities. Experimental examples from the environmental field and in-situ UHV
      film growth will be discussed.

PMID- 11512775
TI  - Synchronous scanning of undulator gap and monochromator for XAFS measurements in
      soft x-ray region.
AB  - Synchronous scanning of the undulator gap and a monochromator was done to obtain
      smooth profiles of incident x-rays that are suitable for XAFS measurements. By
      changing the gap from 150 mm(B=0.12 T) to 140 mm (B=0.15 T) with the use of the
      3rd to 11th harmonic peaks, soft x-rays with energy from 200 eV to 1200 eV were
      obtained. The smooth profile of the incident x-rays provided high-quality
      measurement of XANES and EXAFS spectra in the soft x-ray region. Issues that
      would improve the synchronous scanning system are discussed.

PMID- 11512776
TI  - U7C beamline and XAFS station of national synchrotron radiation laboratory.
AB  - The XAFS station on beamline U7C of National Synchrotron Radiation Laboratory
      (NSRL) was completely constructed in December 1998. The source for XAFS station
      is from a 3-pole superconducting wiggler with magnetic field of 6 T inserted in
      the straight section of the storage ring. Using a Si(111) double crystal
      monochromator with a fixed slit, the X-ray intensity at the sample position is
      about 3x10(9) photons/second at the energy of 8980 eV of Cu K-edge. The Keithley
      65 17 electrometers are used to record the electron charges that are produced in
      the ionization chambers. A high ratio of signal to noise has been obtained for
      the XAFS spectra of Cu, Ni and Fe foils. Furthermore, the XAFS spectrum of Cu
      foil in NSRL is in good agreement with that obtained in BSRF and KEK.

PMID- 11512777
TI  - Mg and Al K-edge XAFS measurements with a KTP crystal monochromator.
AB  - There has been a strong demand for monochromator crystals with a large lattice
      spacing in order to measure EXAFS spectra at the Mg and Al K-edges. We have
      introduced a pair of KTP crystal at BL1A of the UVSOR facility and examined its
      performance in the energy range between 1200 and 2000eV. This crystal
      monochromator can supply stable photon beams enough to measure the EXAFS spectra
      for the Mg and Al K-edges. Advantages of the KTP crystal are discussed in
      comparison with a YB66 crystal monochromator.

PMID- 11512778
TI  - Piezo-QEXAFS: advances in time-resolved X-ray absorption spectroscopy.
AB  - The Piezo-QEXAFS technique is a novel tool for time-resolved X-ray absorption
      spectroscopy in the hard X-ray range. Monochromator components consisting of
      specialized tilt stages to perform fast energy scans, lightweight crystal
      holders, bending mechanics, and control electronics are being installed and
      commissioned. It is planned to perform fast EXAFS scans with time resolution in
      the millisecond range. With Piezo-QEXAFS all typical X-ray absorption experiments
      will be possible as it retains the standard linear geometry. The achieved time
      resolution opens interesting insights into the dynamics of phase transitions and
      chemical reactions.

PMID- 11512779
TI  - Tuning of X-ray phase retarder for magnetic EXAFS spectroscopy in helicity
      modulation mode.
AB  - A technique for polarization tuning over a wide energy range has been developed
      for magnetic EXAFS spectroscopies using a dia mond x-ray phase retarder in
      helicity modulation mode. A quick rocking scan using a piezo stage enabled us to
      tune the angle of retarder crystal with the precision of +/-2 arcsecond within 1
      s. Available energy range of circular dichroism measurements has been extended to
      6-16 keV by adopting not only undulator gap scan but also the present tuning
      technique. This technique has been applied to magnetic EXAFS measurements in pure
      iron at the Fe K-edge. Higher signal-to-noise ratio was obtained in reduced data
      acquisition time.

PMID- 11512780
TI  - Development of multipurpose laboratory XIEES spectrometer and its application to
      surface XAFS analysis of Al2O3 films.
AB  - A new laboratory spectrometer for X-ray Induced Electron Emission Spectroscopy
      (XIEES) has been developed. This spectrometer is suitable for measurements of X
      ray Absorption Fine Structure (XAFS) spectrum in surface sensitive fluorescence
      and electron emission detection modes as well as in standard transmission mode.
      It is the advantage of this spectrometer that a wide range of x-ray energy
      scanning between 0.48 and 41 keV is available. At the Cu K-edge, a energy
      resolution of about 2 eV has been achieved. The spectrometer has been used to
      analyze the Al2O3 (40 A and 500 A)/Si(100) with total electron yield measurement.

PMID- 11512781
TI  - Development of a new in-laboratory XAFS apparatus based on new concept.
AB  - In a conventional in-laboratory XAFS apparatus using conventional X-ray source,
      sealed tube or rotating anode, has been used. In which the X-ray source is fixed
      and the sample is moved (translated and rotated). Hence it has been difficult or
      required a complex method in order to put a heavy element, such as a cryogenic
      cooler, high temperature furnace and an in-situ reacting cell, at a sample
      position. Nowadays, there is a strong demand for obtaining dynamic information of
      a sample and in-situ observation becomes almost unavoidable. We have developed a
      compact X-ray tube and a new goniometer on which X-ray source is moved and
      monochromatic X-ray comes out of goniometer is fixed. Therefore it becomes easier
      to put a various cell at a sample position.

PMID- 11512783
TI  - Experimental technique for radiative-process-resolved X-ray absorption
      spectroscopy at the inner-shell excitation thresholds.
AB  - Partial-fluorescence-yield (PFY) x-ray absorption measurements, rising the
      optimized window widths of position sensitive detectors in wave-length dispersive
      x-ray spectrometers, have been applied for radiative process-resolved (RPR) x-ray
      absorption spectroscopy. We have measured PFY-absorption spectra of graphite and
      diamond at the C K threshold and of h-BN and c-BN at the B K threshold. Resonant
      elastic x-ray scattering was observed in graphite and h-BN on their PFY
      absorption spectra, and excitonic x-ray scattering was observed in diamond and c
      BN. These results show that PFY-absorption measurements for RPR x-ray absorption
      spectroscopy can provide the information about the electronic structures and the
      radiative-decay process in inner-shell excitation.

PMID- 11512782
TI  - Magnetic-field modulation experiments on colossal magnetoresistance samples:
      first results.
AB  - Recently we have observed a small change in the width, sigma, of the Mn-O pair
      distribution function when a IT magnetic field is applied. To improve our
      sensitivity to magnetic-field-induced changes, we have developed a magnetic field
      modulation technique. At each X-ray energy we collect two data points, one with
      field on and the other with field off: as a result we collect two scans
      simultaneously. The difference in these two traces provides a measure of the
      magnetic-field-induced change. The results for the modulation measurements will
      be compared to the earlier work using static magnetic fields.

PMID- 11512784
TI  - X-ray-excited optical luminescence of impurity atom in semiconductor.
AB  - We observed the x-ray-excited optical luminescence (XEOL) of erbium-doped silicon
      (Si:Er) thin films to make a site-selective x-ray absorption fine structure
      (XAFS) measurement of an optically active Er atom. The undulator beam was used
      for the increment of the electron population in the excited state, and following
      XEOL at an infrared wavelength of 1.54 microm with minimum absorption loss in the
      host Si was detected. The edge-jump and XAFS oscillation were successfully
      obtained at the Er L(III)-edge. This spectrum originated from inner-shell
      excitation and relaxation of only the optically active Er atom, indicating that
      site-selectivity at an atomic level was achieved.

PMID- 11512785
TI  - XAFS study on gallium ions implanted in silicon carbide.
AB  - Local structure of gallium ions implanted in silicon carbide has been
      investigated using extended X-ray absorption fine structure on the Ga K-edge. The
      crystallinity of the implantation layer is compared in the samples prepared under
      several different conditions of implantation temperature and post-implantation
      annealing. It is found that significant damage is induced by the implantation at
      room temperature, but the crystallinity recovers by the subsequent annealing at
      high temperature at 1600 degrees C. On the other hand, the best crystallinity is
      obtained by the implantation at high temperature of 500 degrees C. but the
      annealing results in degrading the crystallinity. This indicates an influence of
      the post-implantation annealing at high temperature on the crystallinity in
      atomic level, which relates to the secondary defects in lattice observed by
      electron microscope.

PMID- 11512786
TI  - A position-sensitive ionization chamber for XAFS studies at synchrotron sources.
AB  - A position-sensitive ionization chamber has been developed with backgammon-type
      segmented electrodes. This novel detector possesses a linear range of 8 mm for
      determining the incident position of the X-ray beam incoming. The position
      resolution was found to be less than 10 microm, probably close the sub-micrometer
      region. Owing to its high spatial resolution, the position-sensitive ionization
      chamber was able to commit that the gradual decrease observed in the X-ray beam
      intensity at a SPring-8 beamline was mainly due to the spatial variation of the X
      ray beam in time. The present work also confirmed the applicability of the novel
      detector to the accurate monochromator adjustment for experiments using diamond
      anvil cells.

PMID- 11512787
TI  - A multiwire proportional counter for XAS fluorescence experiments.
AB  - A multiwire proportional counter was used in fluorescence X ray absorption
      measurements and a comparison to a Si(Li) and NaI(Tl) detectors was done. The
      main features of the multiwire proportional counter are its high counting rate
      capability (10(7)) counts x s(-1)) and large active area (6 x 6 cm2). It was
      shown that the MWPC is suitable for fluorescence absorption. Although the maximum
      capability was not reached in the present experiments, it was found that as the
      counting rate increase the MWPC performance became better than Si(Li) detectors
      and shows a similar response to the scintillator counter at medium counting rates
      (up to 10(5) counts x s(-1)).

PMID- 11512788
TI  - Valence selective DAFS measurements of Mn in La1/3Ca2/3MnO3.
AB  - The manganese perovskite system La(1-x)Ca(x)MnO3 displays a complex phase diagram
      of structural, magnetic, and transport properties with varying Ca concentration.
      At x = 2/3 and at low temperature, the system is antiferromagnetic with Mn4+ and
      Mn3+ ions occupying special positions in a charge-ordered supperlattice. The
      charge ordering transition at about 260 K is characterized by the appearance of
      satellite peaks around certain strong normal lattice reflections. The normal
      lattice reflections are due to scattering from planes containing Mn4+ and Mn3+
      ions in nearly stoichiometric proportion, however the superlattice reflections
      are due to scattering from planes containing only Mn4+ ions. By measuring
      Diffraction Anomalous Fine-Structure spectral on a superlattice reflection and
      its associated normal lattice reflection, it is possible to isolate absorption
      like spectra for the two Mn sites. Due to the weak intensity of these
      superlattice reflections, we were unable to obtain high quality near-edge spectra
      for the superlattice reflection measured. However, the data offer useful
      information about the local electronic structures of the two Mn ions.

PMID- 11512789
TI  - Diffraction anomalous fine structure of forbidden reflection of super-ordered
      GaInP.
AB  - We used DAFS to probe super-ordered domains in InGaP/GaAs epitaxial growth. The
      sample was lattice matched InGaP epitaxially grown on GaAs with a substrate
      miscut angle of 6 degrees with respect to the (001) direction. InGaP epi-layer
      exhibited (111)-type alloy ordering, of alternating InP and GaP like planes and
      giving rise to a (-5/2,5/2,-5/2) Bragg peak reflection which becomes allowed.
      Structural data can be extracted, at the same time, for the surroundings of
      Gallium in the bulk and in the epi-layer from allowed reflections, while the
      forbidden reflection gives structural details around Gallium in the ordered
      domains. Difference with the bulk InGaP Fourier transform confirms the symmetry
      selectivity of chosen reflections for the super-ordered domains.

PMID- 11512790
TI  - Diffraction anomalous fine structure of forbidden Bragg reflections: charge
      localization and structure of the octahedral site in magnetite.
AB  - Resonant X ray scattering has been used to investigate charge localization on the
      octahedral iron atoms in magnetite below and above the Verwey temperature. We
      have measured the DAFS spectra of the 002 and 006 "forbidden" Bragg reflections
      permitted by the anisotropy of the iron anomalous scattering factor. We performed
      ab initio calculations which are in fair agreement with the experiment in the
      near edge region and demonstrate the sensitivity of the DAFS spectra to tiny
      structural and electronic changes. No change is observed, in the energy and
      azimuthal dependences, when the sample is cooled down below the Verwey
      temperature. Charge ordering can be definitely excluded and different charge
      localisation schemes discarded. Ab initio simulations, performed by using the
      refined crystallographic structure proposed for the room temperature phase, do
      not show a good agreement with the experiment in the extended region of the DAFS
      spectrum. This point is being investigated.

PMID- 11512791
TI  - Polarization dependence of resonant X-ray emission spectra in early transition
      metal compounds.
AB  - We calculate the polarization dependent spectra of resonant X-ray emission in
      TiF3, VF3 and Cr2O3, which have one, two and three 3d electron(s) in the ground
      state, respectively. We study the detailed mechanism of the spectral structures,
      comparing with a previous result of TiO2. Then we discuss systematically the
      difference of spectra with the change of the 3d electron number from group
      theoretical consideration.

PMID- 11512792
TI  - Multiple scattering approach to DAFS.
AB  - In this article we outline a general approach to the anomalous correction to the
      atomic scattering factor "ab-initio" calculation based on the multiple scattering
      theory. This approach can be used for structural determination in any system and
      in particular in the surfaces where symmetry conditions make usual analysis
      impossible. We show as an application of the formalism calculations related to
      experimental data of bulk Ge.

PMID- 11512793
TI  - Spin-resolved NEXAFS from resonant X-ray scattering (RXS).
AB  - Resonantly excited metal K core line spectra of NiO, MnO, CoO and other compounds
      have been investigated at the beamlines X21 (NSLS/BNL), BW1 and W1.1
      (HASYLAB/DESY). From analysis of spectral data we have drawn the following
      conclusions: -spin conservation is valid in the scattering process, for
      excitations below the absorption threshold as well as above it, -the absorption
      thresholds are different for spin-up and spin-down components of resonantly
      scattered spectra, -quadrupole transitions are very important or even crucial in
      the excitation process. Provided that these conclusions are true, a novel
      technique for quantitative resolution of NEXAFS spectra into spin-up and spin
      down components has been developed. Since the method employs spin conservation
      and local spin references, it needs no circularly polarized radiation and no
      sample magnetization for taking both the RXS and NEXAFS spectra. Hence
      antiferromagnetic and paramagnetic materials can be investigated as well.
      Utilizing linear dichroism by angular-dependent measurements on single-crystal
      samples additional resolution of NEXAFS spectra is possible with respect to the
      orbital symmetry. Application of the method to paramagnetic MnO, for the first
      time, provides new and unambiguous experimental results confirming modern
      (LSDA+U) calculations: The metal K pre-edge XAS of MnO has predominantly 3d(t2g
      and eg) spin-down character. On the other hand, the delocalized p-like states,
      arising from the p-d band effect hybridization have spin-up character.

PMID- 11512794
TI  - Comparison between resonant Lalpha emission spectra and resonant LMM Auger
      spectra of yttrium compounds.
AB  - Resonant Lalpha x-ray emission spectra (RXES) and resonant LMM Auger emission
      spectra (RAES) of Yttrium compounds were measured across YL(III) absorption
      threshold. When the incident photon energy is bellow the absorption threshold,
      only Raman scattering component is commonly observed in both spectra. Above the
      absorption threshold, Raman and normal Lalpha (or normal LMM Auger) emission
      peaks are observed in insulator samples. These spectral features are almost same
      in both RXES and RAES processes, except for the relative intensity ratio between
      these Raman peaks and normal Lalpha (or normal LMM Auger) emission peaks.
      Comparing these two spectra, useful information about the deexcitation of core
      hole can be obtained.

PMID- 11512795
TI  - Resonant X-ray emission spectra of K2Ni(CN)4 x H2O at the Ni K-edge.
AB  - Resonant X-ray emission spectra were measured at the Ni K-edge for a planar low
      spin nickel complex K2Ni(CN)4 x H2O. In the Ni Kbeta emission spectra, a resonant
      X-ray Raman scattering was observed in the pre-edge region, showing linear energy
      dispersion of the emitted photon with the incident photon energy. No energy loss
      features corresponding to the ligand-to-metal charge-transfer (LMCT) was
      identified. The LMCT feature is characteristic of strongly correlated systems
      such as NiO; therefore, the LMCT effect proves to be significantly suppressed.
      This is consistent considering strong covalent character between low-lying pi*
      ligand and metal 3d (occupied) orbitals in low-spin nickel complexes.

PMID- 11512796
TI  - Magnetic circular dichroism of resonant X-ray emission spectra at L edges of rare
      earth compounds.
AB  - We study the resonant x-ray emission spectroscopy (RXES) and the magnetic
      circular dichroism (MCD) at the L2,3 absorption edges of rare-earth elements,
      especially gadolinium ion. To this end, an atomic model is adopted and the
      multiplet coupling effect is taken into account. Using the formula of the
      coherent second order optical process which consists of the excitation process
      from the 2p core state to the empty 5d state and of the radiative decay from the
      3d core state to the 2p core hole, we calculate RXES-MCD spectra. By inspection,
      we have confirmed that the enhancement of the 2p-5d dipole matrix element
      proposed for MCD of x-ray absorption spectroscopy. In addition, characteristic
      features of the spectra observed in gadolinium metallic compounds are reproduced
      by our calculations.

PMID- 11512797
TI  - Multielectron excitations probed by helicity-modulation XMCD at K-edge in 3d
      transition metal compounds.
AB  - Multielectron excitations (MEE) have been investigated using X-ray magnetic
      circular dichroism (XMCD) at the K-edge in 3d transition metal compounds. In the
      range of 50-70 eV above the absorption edge, a dichroic signal that is associated
      with MEE was identified. This phenomenon is thought to occur due to the super
      Coster-Kronig transition described as the final states (1s)1(3p)5(3d)n+2
      resulting from the 3p --> 3d transitions. In order to verify this interpretation,
      XMCD measurements using the helicity-modulation method and calculations of the
      dichroic spectrum were performed based on this super Coster-Kronig transition.

PMID- 11512798
TI  - EELFS study of the cementite local atomic structure.
AB  - The changes in the nearest - neighbour surroundings of carbon atoms in the
      cementite Fe3C lattice due to the heat treatment are analysed by the Extended
      Energy Loss Fine Structure (EELFS) method. To study the local atomic structure of
      the carbon steel U15 after different heat treatment regimes the electron energy
      loss spectra above the C K edge and Fe L2,3 edge were measured. The measured
      experimental EELFS spectra were treated by the standard for the Extended X - ray
      Absorption Fine Structure method procedure using Fourier transformation to obtain
      the parameters of the nearest - neighbour atomic surroundings. Qualitatively the
      assumption was made that the number of the iron atoms in the carbon atom nearest 
      neighbour surroundings changes due to the heat treatment, the evidence of which
      was the change in the ratio of the first two feature intensities of the atomic
      radial distribution function. This assumption is consistent well with the
      previous Mossbauer data.

PMID- 11512799
TI  - Anisotropic features in XMCD spectra.
AB  - We discuss the angular dependent K-edge X-ray Magnetic Circular Dichroism (XMCD)
      spectra based on the semi-relativistic full multiple scattering theory, where 2
      spinor formalism is used to describe spin-orbit coupling. So far most of
      theoretical approaches have been limited to the simplest case where the
      circularly polarized X-ray propagation coincides with the direction of the
      magnetic field. Here we discuss more general cases, using the above theoretical
      approaches. We separately discuss atomic, single and full multiple scattering
      XMCD spectra; in particular anisotropic features of them are studied in detail.

PMID- 11512800
TI  - Magnetic EXAFS at Gd L-edges: the spin-pair-distribution function of Gd
      neighbors.
AB  - The purpose of the experiment is to study the normal and the Magnetic EXAFS
      (MEXAFS) since EXAFS is the method of choice to investigate the local pair- and
      spin-pair-distribution function. We present MEXAFS and EXAFS measurements at the
      L-edges of a Gd single crystal in the temperature range of 10 K to 250 K.
      Therefore we are able to investigate the MEXAFS in a wide range of the reduced
      temperature t=T/Tc of 0.04 < or = t < or = 0.85 with Tc=293 K. We find a strong
      decrease of the nearest neighbor EXAFS which retains only about 35% of its 10 K
      value already at 250 K. This highlights the importance of lattice vibrations. To
      analyze the individual scattering contributions to the MEXAFS and the EXAFS, ab
      initio calculations (FEFF code) have been carried out. The comparison of the
      temperature-dependent damping of the normal EXAFS with the spin-dependent MEXAFS
      allows us to separate the influence of lattice vibrations (Debye temperature 160
      K) from the magnetic ordering (Curie temperature) on the MEXAFS.

PMID- 11512801
TI  - HoFe - Garnet soft XMCD measurements below and above the compensation
      temperature.
AB  - We have investigated the magnetism of Holmium-Iron-Garnet (Ho3Fe5O12) at the Ho
      M4,5 - the Fe L2,3 - and the O K - edges. As expected switching of the sub
      lattice magnetization is observed at the compensation temperature. We will give
      detailed analysis ofthe Ho and Fe XMCD signals, using sum rules. Fe dichroism is
      analyzed in terms of 3d ground state moments and compared to Gadolinium-Iron
      Garnet (Gd3Fe5O12). Contributions of octahedral and tetrahedral Fe sites could be
      separated and analyzed quantitatively. At the oxygen K edge two different
      structures are observable. Those structures show different temperature
      dependencies. Therefore we address these features separately to Fe and Rare Earth
      contributions.

PMID- 11512802
TI  - Variation of XMCD spectrum with temperature at R L2,3-edges in R3Fe5O12 (R=Gd and
      Er).
AB  - The variation of X-ray magnetic circular dichroism (XMCD) with temperature has
      been measured at R L2,3-edges in R3Fe5O12 (R=Gd and Er). A drastic change in the
      spectral profile has been observed at low temperatures. The variation of XMCD
      peak intensity, corrected by the contribution of Fe with temperature, is in
      agreement with the magnetization of R sublattice. The results suggest that Fe 3d
      polarization plays an important role to produce the R L2,3-edges XMCD spectrum.

PMID- 11512803
TI  - Magnetic circular dichroism of 3d5/2 --> 2p3/2 resonant inelastic X-ray
      scattering at the Ho L(III)-edge in Ho3Fe5O12.
AB  - Magnetic Circular Dichroism (MCD) of Resonant Inelastic X-ray Scattering (RIXS)
      of 3d(5/2) --> 2p(3/2) decay (Ho Lalpha1) was measured at the Ho L(III)-edge in
      Ho3Fe5O12. The MCD-RIXS, in which the intermediate state has the 2p4f(n+1)
      configuration due to the quadrupolar transition of 2p --> 4f, was also observed
      at the pre-edge region of the Ho L(III)-edge. The obvious superposition of two
      peaks, which comes from the high-energy off-resonant Raman scattering and the
      fluorescence, could be found in both the RIXS and the MCD-RIXS when the energy of
      the incoming X-ray was 7eV higher than the white line. The dependence of the
      integration of the MCD-RIXS spectra on the incident x-ray energy could roughly
      reproduce the MCD of X-ray absorption spectra (XAS).

PMID- 11512804
TI  - XMCD study of the Ruddlesden-Popper Phase La1.2Nd0.2Sr1.6Mn2O7.
AB  - X-ray Magnetic Circular Dichroism (XMCD) measurements of the Ruddlesden-Popper
      Phase La1,2Nd0,2Sr1.6Mn2O7 are reported. The Mn K. La and Nd L2,L3 edges have
      been measured on a powder sample at two different magnetic fields at low
      temperature. The analysis of the spectra at B = 1T indicates a large orbital
      moment of the Nd 5d-states and a significant spin-polarization of the La 5d-band.
      Furthermore at the Mn K-edge a XMCD-signal is observed, showing a polarization of
      the Mn 4p-band. At lower field (0.2T) all XMCD-signals are about two times
      smaller corresponding to the lower total magnetization. The signal at the Nd L2
      edge vanishes completely at 0.2T.

PMID- 11512805
TI  - Non-symmetric influences in the total electron yield X-ray magnetic circular
      dichroism signal in applied magnetic fields.
AB  - The total electron yield current is strongly influenced by external magnetic
      fields. As known before, this side effect can be slightly reduced by applied
      external bias voltages increasing the total sample drain current nearly up to
      saturation. Nevertheless those effects are not perfectly reduced in almost all X
      ray Magnetic Circular Dichroism (XMCD) applications and are more prominent in
      very small XMCD signals, like O K edge spectra. We show that asymmetries in the
      total electron yield field response will result in XMCD offset signals, which are
      strongly photon energydependent and follow the nonmagnetic absorption signal. A
      simple but effective method to prevent those offset signals, is the use of
      asymmetric magnetic fields. A quantitative analysis and a numerical reduction
      method for those offset signals are shown.

PMID- 11512806
TI  - Quantitative analysis of L-edge white line intensities: the influence of
      saturation and transverse coherence.
AB  - We have performed x-ray absorption spectroscopy at the Fe, Ni, and Co L2,3 edges
      of in situ grown thin magnetic films. We compare electron yield measurements
      performed at SSRL and BESSY-I. Differences in the L2,3 white line intensities are
      found for all three elements, comparing data from the two facilities. We propose
      a correlation between spectral intensities and the degree of spatial coherence of
      the exciting radiation. The electron yield saturation effects are stronger for
      light with a higher degree of spatial coherence. Therefore the observed,
      coherence related, intensity variations are due to an increase in the absorption
      coefficient, and not to secondary channel related effects.

PMID- 11512807
TI  - XAS and MCD studies in Eu0.6Sr0.4MnO3.
AB  - Eu(1-x)Sr(x)MnO3 system is one of the perovskite manganites that exhibit the
      giant magneto resistance effect and the transition from the insulator phase to
      the metal. Eu(0.6)Sr(0.4)MnO3 behaves as a ferromagnetic semiconductor and has an
      Insulator-Metal (IM) transition induced by external magnetic field, which could
      be found only in this system among the perovskite manganites group. The mechanism
      of the transition was investigated by X-ray Magnetic Circular Dichroism (XMCD) at
      the Mn L2,3-edges of and the Eu M4,5-edges in Eu(0.6)Sr(0.4)MnO3.

PMID- 11512808
TI  - X-ray magnetic circular dichroism in FeZrB amorphous alloys: the influence of the
      tensile stress.
AB  - We present X-ray Magnetic Circular Dichroism experiments (XMCD) on the Fe K edge
      of FeZrB metallic glasses performed under tensile stress. In these compounds the
      application of tensile stresses produces a large increase of the Curie
      Temperature. The XMCD signal presents the features expected for a weak
      ferromagnet but a gradual enhancement of the ferromagnetism is observed as boron
      and zirconium concentrations increase. The main effect of the tensile stress is
      to increase the density of states at the Fermi level as deduced from the
      increment of the amplitude of the XMCD signal with the stress.

PMID- 11512809
TI  - X-ray magnetic circular dichroism in cobalt-iron spinels and electronic states of
      Co ions.
AB  - Synchrotron X-ray experiments on magnetic circular dichroism (XMCD) have been
      performed at Co K and Fe K absorption edges for CoFe2O4, Fe(1.5)Co(1.5)O4 and
      FeCo2O4 with the spinel structure. The XANES studies have clarified that only
      Fe3+ exists in all compounds and Co2+ and Co3+ coexist in the latter two
      cobaltites. A systematic change in XMCD spectra has concluded that the Co2+ ions
      in the B sites of FeCo2O4 are in the low-spin state. Since the Co2+ ions in
      CoFe2O4 are in the high-spin state, the spectra of the intermediate cobaltite may
      be explained as a mixture of low-spin and high-spin states.

PMID- 11512810
TI  - Mn K-edge XMCD in Mn3MC (M=Zn and Ga) perovskite.
AB  - Mn3MC (M=Zn and Ga) perovskite has attracted interest because of a variety of
      magnetic phase transitions. In this work, we measure temperature and magnetic
      field dependence of X-ray magnetic circular dichroism (XMCD) at Mn K-edge and
      discuss effect of second constituent metal on the magnetic states of Mn atoms.
      The spectrum in Mn3ZnC is characterized by a dispersion-type profile. In Mn3GaC,
      intensity of the positive peak at the edge is drastically reduced. The difference
      originates in charge transfer from Zn or Ga to Mn atoms. Temperature and magnetic
      field variations of the Mn K-edge XMCD spectrum suggest that orbital magnetic
      moments are closely related to the magnetic phase transition.

PMID- 11512811
TI  - Electronic states in Cu2MnX (X=Al, In, and Sn) Heusler alloy studied by XMCD and
      multiple scattering calculations.
AB  - X-ray magnetic circular dichroism (XMCD) has been measured at Mn and Cu K-edge in
      Cu2MnX (X=Al, In, and Sn) Heusler alloy. The Mn K-edge spectrum shows a
      dispersion-type profile and the Cu K-edge resembles the Mn spectrum, which
      suggests that polarization of the p unoccupied bands originates commonly in Mn 3d
      states. To reproduce the observed spectrum by full multiple scattering
      calculations. Madelung potential has been taken into account. Charge
      redistribution is an important factor for the electronic structure in Cu2MnX
      Heusler alloy.

PMID- 11512812
TI  - Magnetic circular dichroism at transition metal L2,3 edges in D03-type (Fe(1
      x)Mn(x))3Al alloys.
AB  - We have measured magnetic circular dichroism (MCD) spectra at the transition
      metal L2,3 edges in D03-type (Fe(1-x)Mn(x))3Al in order to investigate their
      local magnetic moments. The analysis of the spectra shows that Fe has moments
      much larger than Mn, whose moment is ferromagnetically coupled with the Fe one.
      This does not lend support to the antiferromagnetic mechanism proposed for the
      reduction in magnetization as well as a large Mn moment predicted for x = 1/3.
      The evolution of satellites found in the Mn spectrum with x increased suggests
      that the change in the electronic state may result in the magnetization
      reduction.

PMID- 11512813
TI  - Magnetic circular dichroism at transition metal L2,3 edges in D03-type (Fe(1
      x)Vx)3Al alloys.
AB  - Magnetic circular dichroism (MCD) spectra have been measured at the Fe and V L2,3
      edges of DO3-type (Fe(1-x)Vx)3Al in order to investigate their local magnetic
      moments and electronic structures. Large MCD is observed at the Fe L2,3 edges,
      while the V L2,3 MCD shows relatively small intensity with complicated features.
      Signs of these MCD spectra indicate an antiferromagnetic coupling between the
      magnetic moments on Fe and V. According to the analysis based on the magneto
      optical sum rules, the magnetic moment decreases with x, but remains fairly large
      for Fe2VAl, which might arise from its marginally magnetic nature.

PMID- 11512814
TI  - Natural linear dichroism in pyrite (FeS2): experiments and calculations.
AB  - Electric quadrupole transitions are revealed through the angular dependence of X
      ray absorption spectra in a cubic crytal. Data collection was achieved at the
      iron K-edge in pyrite (FeS2) by using the angular moment method developed for X
      ray Natural Circular Dichoism (XNCD) measurements. The natural linear dichroism
      (XNLD) was found to be around 0.5% of the edge jump. Experimental results are
      compared with monelectronic and multilectronic calculations. Calculations allow
      to quantitatively determine the proportion of quadrupolar transitions in the pre
      edge structure and the anisotropy is explained in terms of structural and
      electronic parameters.

PMID- 11512815
TI  - Magnetisation reorientation in ultra-thin Fe films on Cu(100) upon deposition of
      Co.
AB  - Ultra thin films of Fe deposited on the (100) surface of a Cu single crystal
      exhibit a net perpendicular magnetic anisotropy. The addition of very low
      coverages of Co results in the easy magnetic direction reorienting into the film
      plane. This behavior is in contrast to the addition of similar amounts of Fe,
      whereupon the ferromagnetic response vanishes. This result is discussed in terms
      of the anisotropy energies derived from the spectroscopic data.

PMID- 11512816
TI  - Linear dichroism in 3d transition metal NEXAFS of correlated materials.
AB  - Investigations of 3d transition metal (TM) compounds by means of linear dichroism
      in TM K-NEXAFS will be reported. At this, the decomposition of the angular
      dependent NEXAFS into orbital projected components are important problems. A
      survey is given on methods how to extract information on the geometrical,
      electronic and magnetic structure from linearly polarized NEXAFS and EXAFS
      spectra. New results on CuO and CuPc (Copper Phthalocyanine) are reported. A
      reference is given to the novel method for spin-resolving of NEXAFS by analysis
      of resonantly scattered X-ray core lines.

PMID- 11512818
TI  - XAFS XI and new sources in Europe--SLS, SOLEIL and DIAMOND.

PMID- 11512817
TI  - Photon-stimulated ion desorption from molybdenum oxides following Mo 2p3/2
      excitation.
AB  - Photon-stimulated ion desorption from solid MoO3 following the Mo 2p3/2 resonant
      transition has been investigated. In the XANES spectrum, Mo 2p3/2 peak is split
      into two components corresponding to the excitations from Mo 2p3/2 into the t2g
      and e(g) orbitals. It was observed that the desorption yield of O+ ions at the Mo
      2p3/2-->e(g) resonance is higher than that at the Mo 2p3/2-->t2g resonance. The
      Auger decay spectra reveal that there exist two kinds of spectator Auger decays.
      The high desorption yield at the 2p3/2-->e(g) resonance is interpreted by the
      fast breaking of the Mo-O bond due to the localization of the electrons in the
      highly antibonding e(g).

PMID- 11512819
TI  - Element-specific magnetization curves and crossover in Co/Cu/Ni/Cu(001) trilayers
      studied by XMCD.
AB  - We present temperature-dependent measurements via the element-specific XMCD
      technique for Co/Cu/Ni trilayers for cases where the ordering temperature of Co
      is lower than the one of Ni. Our work focuses mainly on the influence of the
      interlayer coupling on the shape of the temperature-dependent magnetization
      curves of Ni. By electing 1.3 ML of Co and 4 ML of Ni we get a lower T(C)(Co)
      approximately 90 K and a higher T(C)(Ni) approximately 180 K. The crossing of the
      M(T) curves leads to a rotation of the remanent magnetization of Ni. A case where
      the sublayer magnetizations change gradually their angle as a function of the
      temperature is recorded and attributed to a competition between coupling and
      anisotropy mechanisms.

PMID- 11512820
TI  - XAFS studies of the formation of cobalt silicide on (square root of 3 x square
      root of 3) SiC(0001).
AB  - Thin Co films (1-8 nm) were directly, sequentially, and co-deposited with Si (3.6
      29.2 nm) on the (square root of 3 x square root of 3)-R30 degrees reconstruction
      of 6H-SiC(0001). The films were annealed over a temperature range of 823-1373K
      and investigated with XAFS, XPS, AES and AFM. After annealing up to 1373K
      directly deposited Co films do not transform entirely to cobalt disilicide and C
      segregation is observed on the surface of the films. On the other hand,
      sequentially and co-deposited films do form cobalt disilicide after annealing at
      823K, but also show islanding after annealing at 923K.

PMID- 11512821
TI  - Reflection mode XAFS investigations of reactively sputtered thin films.
AB  - Amorphous Ta-oxide and Sn-nitride thin films were prepared by reactive sputter
      deposition on smooth float glass substrates and investigated ex situ using
      reflection mode XAFS. The absorption coefficient mu and its fine structure were
      extracted from the measured reflection mode XAFS spectra with a method based on
      the Kramers-Kronig transform. Bond distances, coordination numbers and Debye
      Waller factors were determined by a detailed XAFS data analysis and compared to
      those of reference compounds. In addition, changes of the atomic short range
      order of the sputter deposited Ta2O5-films induced by a thermal heat treatment in
      ambient air were examined as a function of the annealing temperature.

PMID- 11512822
TI  - XAFS study on active Pr sites in zeolite as a photocatalyst for decomposition of
      nitrous oxide.
AB  - The praseodymium-exchanged mordenite degassed at 873 K acted as a highly active
      heterogeneous photocatalyst for the stoichiometric decomposition of N2O. Analysis
      of Pr L3-edge EXAFS revealed that the Pr species were isolated each other in the
      large channel of zeolite, and that the active Pr species were coordinated by ca.
      four oxygen atoms and one Al atom. On the other hands, the inactive Pr species
      are surrounded by ca. 10 oxygens of adsorbed waters. The former low-coordinated
      Pr species allowed a strong adsorption of N2O, which could be the first step of
      the decomposition reaction.

PMID- 11512823
TI  - In situ EXAFS investigation of carbon-supported Pt clusters under potential
      control.
AB  - The transformation of carbon supported Pt clusters under potential control in 1M
      HClO4 solution was investigated by in-situ X-ray absorption spectroscopy
      measurements. Both XANES and EXAFS data are used to show the structure evolution
      of the Pt clusters at various potentials. It showed that the white line area and
      the edge energy increase with the applied potential in the range 0.1-1.5V. The
      coordination number of oxygen and platinum on the Pt/C electrode increases and
      decreases, respectively, with the applied potential. It is found that the size of
      Pt cluster does not grow during the electrode fabrication. However, the
      crystallization of Pt cluster occurs during the potential cycling.

PMID- 11512824
TI  - In situ observation of pitting of stainless steel by XAFS.
AB  - An in situ observation technique by XAFS (X-ray Absorption Fine Structures) has
      been developed for observation of metal corrosion. XAFS spectra were obtained
      with a special electrochemical cell to elucidate pitting: change of
      concentrations and structures of ions near the interface of solution and metal.
      It has been successfully shown that the concentrations of Cr and Br are linearly
      dependent on the distance from the interface. Also, salt formation at the
      interface and the hydrolysis reaction far from the interface are indicated.

PMID- 11512825
TI  - Musings about the development of XAFS.
AB  - A personal recollection of the development of X-ray absorption fine structure
      (XAFS) into a structure-determination technique is presented. Because of
      confusion in the theoretical explanation of the 'Kronig structure', now called
      EXAFS, the extended XAFS, its explanation remained unresolved for about 40 years.
      As I was introduced to the EXAFS phenomenon by Farrel Lytle and saw his
      impressive data, the thought came to me that scattering of the photoelectron from
      surrounding atoms could be the mechanism of the effect. My graduate student, Dale
      Sayers, agreed to work on developing the theory under my supervision and to make
      EXAFS measurements under Lytle's supervision as his PhD thesis. The theory led to
      the idea of a Fourier transform of the EXAFS, which showed peaks from surrounding
      atoms, proving the validity of the theory and suggesting the method of structure
      determination by using standards from known structures. Within a few years,
      facilities at synchrotron sources were developed to measure XAFS, opening up the
      technique to the general scientific community. In spite of some initial growing
      pains, XAFS has matured into a powerful technique for local structure and has
      been applied to obtain magnetic structure, in addition to distribution of atoms.
      Other related techniques have been spawned from XAFS, expanding the impact of the
      original phenomenon.

PMID- 11512826
TI  - XAFS analysis of corroded metal surfaces with molten salts by conversion-electron
      yield method.
AB  - We have measured XAFS spectra of metal surfaces corroded with melting salt (NaCl,
      KCl, and Na2SO4). Steel samples used were S45C, SCM435, SUS310S, and SUS304. We
      measured the Fe K-edge XAFS spectra for all samples and the Ni K-edge for SUS310S
      and SUS304 samples before and after the corrosion. The XANES spectra of samples
      before the corrosion show metallic structure because surface oxide thickness is
      thinner than probing depth with a conversion yield XAFS method. Each result of
      these XAFS spectra gives good agreements with the FEFF calculation in the
      assumption of bcc and/or fcc structure. The Fe K-edge spectra of steel samples
      except SUS310S after corroded treatment show existence bonding between Fe and
      another light element although the spectra of SUS310S samples before and after
      corroded treatment are much the same.

PMID- 11512827
TI  - EXAFS study of NiAl in thin films.
AB  - Technologically important coatings of transition-metal aluminides call be
      produced by thermal or ion beam mixing of multilayer structures sputter deposited
      on substrates. The quantitative detection of constituents by depth profiling is
      sufficient to establish the efficiency of mixing methods. However, to decide
      whether a mixture of nanoparticles or a stoichiometric alloy is formed, EXAFS
      analysis of the local atomic neighborhood in the film is required. Ni K edge
      EXAFS spectra are measured on a series of samples of Ni/Al multilayer on Si(111)
      surface, after ion mixing at different substrate temperatures. The spectra show
      that with increasing temperature the nickel aluminide phase gradually substitutes
      the Ni fcc metal phase.

PMID- 11512828
TI  - X-ray absorption spectroscopy study of Co structure in the epitaxial Co/Pt
      multilayers on Al2O3(11-20) substrates.
AB  - In this study, five epitaxial [Co(t nm)/Pt(1 nm)]30, multilayer samples (t=0.16
      1.07 nm) were studied using polarized X-ray absorption spectroscopy method. These
      samples were prepared on Mo(110)/ Al2O3(11-20) substrates by MBE technique. The
      results show that the Co layer is more like an fcc pseudomorphic structure for
      the Co thickness of less than 0.3 nm. For Co layer thickness of 1 nm, the first
      shell distance is 0.25 nm, which is very close to the Co-Co distance of bulk hcp
      Co. On the other hand, for Co layer of less than 0.3 nm, the in plane first shell
      distance is expanded by 4% and most of the neighboring atoms are Pt atoms. The
      fitting results of the Co/Pt multilayers seem to support a sharp boundary model
      rather than an interdiffusion model.

PMID- 11512829
TI  - Study by X-ray absorption spectroscopy of Si3N4 films after Cu or Fe implantation
      and thermal treatment.
AB  - Si3N4 amorphous thin layers prepared by sputtering have been implanted either
      with Cu or with Fe ions. X-ray absorption spectroscopy was performed at the Si K
      edge to characterise the electronic empty states of p character, the structural
      state of the initial layers and the modifications around Si induced by
      implantation and a post-annealing treatment. We show that the energy deposition
      process mainly leads to a reorganisation of the second coordination shell around
      Si, i.e. concerns the Si-Si bonds.

PMID- 11512830
TI  - A grating monochromator of BL23SU at SPring-8 covering silicon and oxygen K
      edges.
AB  - We report the present performance of a grating monochromator at the newly
      constructed soft x-ray beamline (BL23SU at the SPring-8), which can measure both
      silicon and oxygen K-edges. That provides new opportunities for XAFS measurements
      of solids up to 2100 eV.

PMID- 11512831
TI  - Thermal effect in unoccupied molecular orbitals of C60 molecules adsorbed on a
      Si(001)-(2 x 1) surface studied by NEXAFS.
AB  - We report here the temperature-dependent unoccupied molecular orbitals (MO's) of
      C60 molecules adsorbed on a Si(001)-(2 x 1) surface measured using near edge x
      ray absorption fine structure (NEXAFS). At 300 K, the NEXAFS spectrum reveals
      that the interaction between a 1.0 monolayer (ML) C60 film and a Si(001) surface
      is mainly the van der Waals force. After annealing the samples at 500 K, we
      observe an increment in the full-width at half-maximum of unoccupied MO's, which
      indicates the change of the interaction. Moreover, the lowest unoccupied
      molecular orbital (LUMO) shifts to the higher photon energy side and the
      intensity of the LUMO+1 relative to that of the LUMO+3 decreases in the NEXAFS
      spectrum. These results suggest that the strong interaction induced at 500 K has
      a covalent character, to which the LUMO+1 contributes.

PMID- 11512832
TI  - Three-dimensional analysis of the local structure of Cu on TiO2(110) by in situ
      polarization-dependent total-reflection fluorescence XAFS.
AB  - Cu K-edge XAFS of Cu/TiO2(110) was measured by polarization-dependent total
      reflection fluorescence XAFS technique. XAFS of [001], [110], and [110]
      directions were measured to elucidate the three dimensional structure of Cu
      species on the TiO2(110) surface prepared by the deposition of Cu(DPM)2 followed
      by reduction with H2. Simulation of the EXAFS functions as well as conventional
      curve fitting analysis revealed that plane Cu3,4 small clusters with similar
      structure to Cu(111) plane were formed by the reduction at 363 K. The small
      clusters converted into spherical metallic Cu particles by the reduction at 473
      K.

PMID- 11512833
TI  - Local structure of Ge nanocrystals embedded in SiO2 studied by X-ray absorption
      fine structure.
AB  - Local structure of Ge nanocrystals embedded in SiO2 has been studied by X-ray
      absorption fine structure on the Ge K-edge. The XANES and EXAFS results indicate
      that Ge atoms in samples with the Ge concentration x=25-40 mol. % are coordinated
      with oxygen atoms, while they exist as amorphous Ge clusters in samples with x=60
      mol. %. Upon annealing, completely relaxed crystalline Ge phase is formed for
      samples with x=60 mol. %, in contrast to the x=25-40 mol. % sample, which show
      little or no indication of Ge cluster formation. A possible mechanism of Ge
      nanocluster formation is discussed.

PMID- 11512834
TI  - Atomic surrounding of Co implanted in AIN at high energy.
AB  - AlN bulk ceramic has been implanted with energetic Co ions. In order to
      accurately characterise the atomic surrounding of the implanted ions. X-ray
      absorption measurements were carried out at 80 K in the fluorescence mode at the
      Co K edge in the as-implanted and annealed states. Simulation of the EXAFS
      oscillations allowed us to identify a first stage where Co is inserted in the AlN
      matrix followed by a second stage where Co precipitates form.

PMID- 11512835
TI  - In situ XAS characterization of the electrochemical insertion of copper in
      polypyrrole films.
AB  - We report the electrochemical insertion of copper in polypyrrole films followed
      by XAS spectroscopy. Depending on the applied potential the copper remains as an
      ionic form like Cu(+n)-(OSO3-)n. For more reductive potentials metal particles
      are synthesized. Small particles with an estimated average diameter of 20 A were
      obtained.

PMID- 11512836
TI  - Local structure of NiTi nanocrystals studied by EXAFS and XRD.
AB  - A series of NiTi nanocrystals with different annealing temperatures, prepared by
      sputtering method, were investigated by extended x-ray absorption fine structure
      (EXAFS) and x-ray diffraction. It was found that the structure of nano-phase
      powder is different from bulk NiTi alloy with bcc structure as target materials.
      When increasing the annealing temperature, a small fraction of the (Ni,Ti) type
      nanocrystal with the hexagonal structure was presented except target materials
      and Ni, and it is atomic occupation in random. Finally there were four Ti and two
      Ni atoms around central Ni atoms, and the bond length of Ni-Ti and Ni-Ni were
      0.2462nm and 0.2585nm at 800 degrees C annealed.

PMID- 11512837
TI  - XAS investigation of Al2O3-coated nano-composite ZrO2.
AB  - In order to complement the structural characterisation by high resolution
      electron microscopy and perturbed angular correlation spectroscopy (PAC) of Al2O3
      coated nano-composite ZrO2, XAFS spectra have been acquired and analysed. The
      electron micrographs showed fringes of a well ordered lattice and well defined
      crystal faces of the as-produced powder whereas the PAC spectra indicated a
      strongly distorted short range order. On the basis of the XAFS data, a structural
      model for the ZrO2 core of the nano-composite ZrO2/Al2O3 with a well ordered Zr
      lattice and a sevenfold, strongly distorted nearest neighbour oxygen shell is
      proposed. A smooth temperature dependence without an indication for a phase
      transformation up to a temperature of 700K has been revealed.

PMID- 11512838
TI  - Adsorptive properties of metal oxide dispersed carbon materials and
      characterization of metal oxide fine particles by XAFS.
AB  - Surface modification of activated carbon fiber (ACF) with metal oxide increases
      the adsorptivity of the ACF for supercritical gas such as NO and CH4. In this
      study, pitch-based activated carbon fibers (P20) were modified with nickel oxide
      particles. The adsorptive properties and micropore structures of NiO dispersed
      P20 (NiO-P20) were investigated by nitrogen adsorption isotherms at 77 K. The
      isotherm was of type 1, suggesting that the NiO-P20 has microporosity. The
      micropore volume and surface area for NiO-dispersed P20 were smaller than that of
      P20 by about 15%. The Ni K-edge X-ray absorption fine structure of NiO-P20 has
      been investigated in order to characterize the species dispersed on P20. The
      local structure of the NiO particles on the P20 showed some different features
      compared with the local structure of powdered NiO.

PMID- 11512839
TI  - EXAFS study of the Fex/ZrO2 composite nanomaterials obtained by sol-gel
      synthesis.
AB  - The local Zr and Fe arrangements in the nanocomposite system Fe(x)/ZrO2 (x=0-0.2)
      obtained by sol-gel method were studied by EXAFS. The phase composition was found
      to vary significantly on iron loading. For the samples calcined at 500 or 600
      degrees C, at x< or =0.01, the formed ZrO2 is a mixture of monoclinic and
      tetragonal structures. Only tetragonal structure is revealed at x > or = 0.05
      with the exception of Fe0.2/ZrO2, calcined at 500 degrees C, where new non
      typically short Zr-Zr distances (3.29, 3.43A) were observed. At low iron loading
      (less than one monolayer) Fe3+ ions were found to localize within the pre-surface
      layers of ZrO2 nanoparticles showing property of isolated ions. For greater Fe
      loading, iron exhibits either two-dimensional layer structure or two-phase
      system.

PMID- 11512840
TI  - XANES study on the valence transitions in cerium oxide nanoparticles.
AB  - The aim of this work is the determination of Ce environment and valence state in
      Cerium oxide nanoparticles prepared by the microemulsion method. X-ray absorption
      near-edge structure measurements at Ce L3 edge were performed on the
      nanoparticles as a function of annealing temperature, ranging from 298K to 873K
      under air condition. The experimental results support the conclusion that Ce ion,
      in the investigated systems, is in trivalence state when the annealing
      temperature is below 473K. As the temperature increases up to 623K, the XANES
      spectrum shows the coexistence of Ce3+ and Ce4+ states. When the temperature is
      higher than 623K, the spectra become identical to that of CeO2 with a distinct
      double-peak structure, corresponding to the Ce4+ state.

PMID- 11512841
TI  - Ni clay neoformation on montmorillonite surface.
AB  - Polarized extended X-ray absorption fine structure spectroscopy (P-EXAFS) was
      used to study the sorption mechanism of Ni on the aluminous hydrous silicate
      montmorillonite at high ionic strength (0.3 M NaClO4), pH 8 and a Ni
      concentration of 0.66 mM. Highly textured self-supporting clay films were
      obtained by slowly filtrating a clay suspension after a reaction time of 14 days.
      P-EXAFS results indicate that sorbed Ni has a Ni clay-like structural environment
      with the same crystallographic orientation as montmorillonite layers.

PMID- 11512842
TI  - Glancing-angle diffraction anomalous fine structure of InAs quantum dots and
      quantum wires.
AB  - We have performed Diffraction Anomalous Fine Structure measurements at the As K
      edge of self-growth InAs/InP(001) Quantum Wires and InAs/GaAs(001) Quantum Dots.
      The samples have been grown by Molecular Beam Epitaxy and their equivalent
      thickness is of 2.5 monolayers. We have measured the (440) and (420) Bragg
      reflections in glancing-angle scattering geometry, at incidence angles close to
      the substrate critical angle. We demonstrate the feasibility of the experiment
      reporting, for the first time. Diffraction Anomalous Fine Structure spectra of
      such low coverage epitaxial layers, and we show that the analysis of the
      Diffraction Anomalous Fine Structure lineshape together with the analysis of
      oscillatory part of the signal, can provide information about composition and
      strain of the nanostructures.

PMID- 11512843
TI  - Temperature dependence of thermal expansion coefficient of silver nanoparticles
      and of bulk material determined by EXAFS.
AB  - The thermal expansion behaviour of silver fcc has been described by an anharmonic
      Einstein model using EXAFS data in the temperature range between 10 and 300 K.
      The linear expansion coefficient of a bulk silver foil agrees well with X-ray
      diffraction data. In the case of silver particles embedded in a silicate glass
      matrix, this parameter shows an increase for particles of 3.2 nm in size by 70%
      whereas samples with an average size of particles of 5.1 nm show no changes
      compared with bulk fcc. The increase for small particles reflects the size effect
      as well as the influence of the surrounding matrix of glass. The results reveal a
      substantial influence of the distribution of particle sizes on the expansion
      coefficient.

PMID- 11512844
TI  - A new method for the size-selective EXAFS of neutral free clusters.
AB  - Recently we have measured Photoelectron Photoion Coincidence (PEPICO) spectra for
      selenium dimer Se2 and larger species such as Se5 at the beamline BL-12C in
      Photon Factory. The PEPICO spectra reveal that the multiply charged ions, Se(z+),
      are produced as a result of de-excitation processes following the inner-shell
      excitation and fragmented to atomic ions owing to the Coulomb explosion. The
      branching ratios from the parent clusters to the daughter ions exhibit clear
      dependence on the size of the parent clusters. In particular, the branching
      ratios in the non-resonant absorption region are well reproduced by assuming that
      the charges are randomly distributed within the clusters before the Coulomb
      explosion. Based upon these findings, we propose a new method for the size
      selective EXAFS of neutral free clusters by utilizing the PEPICO measurements.

PMID- 11512845
TI  - XAFS studies of gold and silver-gold nanoparticles in aqueous solutions.
AB  - The x-ray absorption fine structure (XAFS) of colloidal Au and Au/Ag
      nanoparticles (3.5nm and 20nm mean diameter) in an aqueous solution has been
      investigated. Size dependent alloying was observed upon deposition of Ag on Au
      core. Ag forms distinct layers around the 20 nm Au nanoparticles. In contrast,
      random mixing is found for Ag deposited on 3.5nm Au particles.

PMID- 11512846
TI  - Verification of NEXAFS assignments by a comparison of fragmentation between
      gaseous and condensed methyl formate.
AB  - According to the ion desorption from condensed methyl formate (DCOOCH3) by C 1s
      electron excitation, C+ yield was strongly enhanced at 289.1 eV, a higher energy
      side of C1s(DC) --> pi*(C=O) peak. This feature could not be clearly assigned. In
      this work, to clarify the feature, fragment-ion yield curves of gas-phase methyl
      formate were measured and compared with those of condensed one, since gas-phase
      and condensed systems are presumed to show more or less similar fragment-ion
      yield curves under similar excitations. The results demonstrate that fragment-ion
      yield curves are useful for the assignments of NEXAFS features in both gaseous
      and condensed polyatomic molecules.

PMID- 11512847
TI  - The role of XAFS in the in situ and ex situ elucidation of active sites in
      designed solid catalysts.
AB  - New mesoporous and microporous catalysts based on silica, aluminophosphates, or
      aluminophosphates containing one or other of the heteroatoms Ti, Co, Mn, Fe and
      Cr, are ideally suited for study by X-ray absorption fine structure (XAFS). The
      information derived from X-ray absorption near-edge structure (XANES) and
      extended X-ray absorption fine structure (EXAFS) elucidates the nature of the
      catalytically active site, generally (but not invariably) under in situ
      conditions. This, in turn, provides new insights into the mechanism of the
      catalysis and suggests methods of improving the performance of the original
      catalyst. In this way, significant advances have recently been made in designing
      catalysts for the selective oxidation of alkanes, for the epoxidation of alkenes
      and for the dehydration of alcohols to yield olefins. Combined with density
      functional theory (DFT) computations, XAFS studies have also yielded fresh
      insights into the architecture of nanoparticle catalysts, such as Ru12Cu4C2
      supported on mesoporous silica.

PMID- 11512848
TI  - XAFS study on metal endohedral fullerenes.
AB  - Structure of metal endohedral fullerenes is studied by XAFS and XANES. The Sc-Sc
      distance of 2.23(1) A determined from Sc K-edge XAFS supports the formation of a
      triangular Sc3 cluster in Sc3@C82 as is found by MEM analysis for the X-ray
      diffraction. Gd L(III)-edge XAFS of Gd@C82 shows that the first and the second
      neigboring Gd-C distances are 2.51(2) and 2.85(4) A, respectively. The La-La
      distance of La2@C80 has been determined to be 3.90(1) A at 40 K. This value does
      not change when increasing temperature [3.90(2) A at 240 K]. The position and the
      valenece of the Eu atom in Eu@C60 are also discussed based on Eu L(III)-edge XAFS
      and XANES.

PMID- 11512849
TI  - Li K-edge spectra of lithium halides.
AB  - We measured the Li K-edge spectra of lithium halides by means of total electron
      yield method (TEY), using the soft x-ray Beam Line 2 (BL2) of the compact
      synchrotron radiation facility at Ritsmeikan University in Japan. In lithium
      halides, the spectra have a sharp peak at about 60eV and a broad peak at the
      higher energy side. Various peak structures that appear in the absorption spectra
      are assigned to the corresponding Li-1s to valence band free orbitals
      transitions, which have been calculated by the Discrete Variational (DV)-Xalpha
      molecular orbital calculation method.

PMID- 11512851
TI  - XAFS study of the additive cation effect on the oxidation-resistance of platinum
      catalyst.
AB  - The additive cation effect on the oxidation-resistance of platinum supported on
      alumina was investigated by Pt L(III) and L(II)-edge XAFS. The white line
      intensity at Pt L(III)-edge of oxidized catalysts decreased with an increase in
      the electronegativity of the additive cation in the same way as the support
      effect previously reported: The addition of electrophilic cations make the
      supported platinum less oxidized state compared with the original Pt/Al2O3 and
      vice versa. Thus, it was revealed that the addition of more electrophilic cations
      provides the higher oxidation-resistance to platinum catalyst, even when platinum
      is supported on basic oxides.

PMID- 11512850
TI  - Local structure of silver clusters in the channels of zeolite 4A.
AB  - The Ag K-edge EXAFS measurements have been carried out at 50 K for fully Ag+
      exchanged zeolite 4A (Ag-4A) dehydrated at different temperatures under vacuum.
      In the Fourier transforms of the EXAFS oscillation the two distinct peaks appear
      around 2.2 A and 3.0 A, and a shoulder around 2.8 A. The structural parameters
      (distance, coordination number and root mean square displacement) were derived by
      a three-shell (two Ag-O contacts and Ag-Ag contact) curve-fitting analysis. It is
      found that a silver cluster is formed with Ag-Ag distance 2.82+/-0.02 A and
      coordination number 4.9+/-0.2. When the silver cluster is formed 6 Ag0 atoms and
      8 Ag+ ions are arranged in a cubic closed-packed manner in the cage of the Ag-4A
      zeolite. The 8 Ag+ ions and 6 Ag0 atoms are confined in the framework of oxygens
      at distances of 2.28+/-0.02 and 2.88+/-0.02 A, respectively.

PMID- 11512852
TI  - Manganese, iron and sulfur K edge XAFS of promoted sulfated zirconia catalysts.
AB  - Promoted sulfated zirconia samples were prepared by the incipient wetness
      technique to produce isomerization catalysts which were active for the conversion
      of n-butane to isobutane at 338K (up to 10% conversion of 1% n-butane, 1atm.,
      0.25 h(-1) WHSV). The local structure of Fe and Mn in promoted sulfated zirconia
      was investigated using fluorescence yield XAS. Spectra were taken of calcined
      samples, activated samples, and samples after reaction with n-butane (maximum
      activity and deactivated). Factor analysis reveals that the Mn K edge XANES can
      be described by a linear combination of the spectra of two separate components,
      and that the ratio of these components changes with activation of the catalyst,
      and during use in the n-butane isomerization reaction. The change in ratio of the
      Mn species during activation and reaction results in a reduction of the average
      Mn valence from 2.4 to 2.2. The Fe K edge XANES was not similarly affected by
      activation and reaction with n-butane.

PMID- 11512853
TI  - Annealed crystallization of ultrafine amorphous NiB alloy studied by XAFS.
AB  - XAFS has been used to investigate the local structure evolutions of ultrafine
      amorphous NiB alloy during the annealed crystallization process. A
      nanocrystalline Ni phase with the local structure of crystalline Ni-like and a
      crystalline Ni3B, have been produced for ultrafine amorphous NiB alloy under the
      annealed temperature of 573 K. The results rule out Rojo et al.'s devitrification
      mechanism of Ni80B20 amorphous alloy in which they considered that an amorphous
      pure Ni phase is formed in the first exothermic process. However, our results are
      almost identical with Riveiro et al.'s conclusion in which the intermediate state
      is interpreted as two metastable crystalline phases of Ni3B and Ni-rich NiB
      alloy. With the annealed temperature going onto 773 K, the ultrafine NiB sample
      is further decomposed and crystallized into crystalline Ni with long-range order.

PMID- 11512854
TI  - Application of ion beam techniques for preparation of metal ion-implanted TiO2
      thin film photocatalyst available under visible light irradiation: metal ion
      implantation and ionized cluster beam method.
AB  - Transparent TiO2 thin film photocatalysts have been prepared on silica glass
      plate by an Ionized Cluster Beam (ICB) method. In order to improve the electronic
      properties of these photocatalysts, transition metal ions (V+, Cr+, Mn+, Fe+)
      were implanted into the TiO2 thin films at high energy acceleration using an
      advanced metal ion-implantation technique. The combination of these ion beam
      techniques can allow us to prepare the TiO2 thin film photocatalysts which can
      work effectively under visible light (lambda>450 nm) and/or solar light
      irradiation. The investigation using XAFS and ab initio molecular calculation
      suggests that the substitution of octahedrally coordinated Ti ions in TiO2
      lattice with implanted metal ions is important to modify TiO2 to be able to
      adsorb visible light and operate under visible light irradiation.

PMID- 11512855
TI  - Fluorescence EXAFS for the in situ study on the state of promoters in catalysis.
AB  - The fluorescence EXAFS (FLEXAFS) technique has been combined with an in situ cell
      and on-line gas analysis. For this purpose a seven-element silicon drift detector
      has been used, which has high count rate capabilities and can be operated at room
      temperature. The potential of this technique is shown by the study of the state
      of copper promoter atoms in Fe-Cr based high temperature shift (HTS) catalysts.
      The FLEXAFS measurements revealed that Cu (0.17-1.5 wt%) is present in the
      metallic state under working conditions of the catalysts but easily re-oxidizes
      upon air exposure. The reduction behaviour of copper depends strongly on the
      copper concentration and the pre-treatment, i.e. if the catalysts have been
      calcined or used in the HTS reaction. For used catalysts, a Cu(I) phase was
      detected as intermediate during reduction. Its stability was especially high at
      low copper concentration.

PMID- 11512856
TI  - EXAFS determination of the size of Co clusters on silica.
AB  - The metallic Co catalyst for the Fischer-Tropsch reaction is prepared by
      reduction of Co salts impregnating microporous silica. The average size of the
      metallic Co clusters is determined from the average number of neighbours deduced
      from Co K-edge EXAFS of catalyst samples. A model EXAFS signal constructed from
      the scattering paths of Co metal fcc lattice with lengths up to 5 A is calibrated
      on a reference spectrum of Co metal foil. Catalyst spectra are interpreted with
      the same model expanded with variable neighbour fractions of the four nearest
      shells. Cluster size is obtained from comparison with the neighbour-fractions of
      consecutive fcc magic-number clusters.

PMID- 11512857
TI  - Pt L-edge XANES as a probe of Pt clusters.
AB  - The sensitivity of Pt L-edge XANES to local geometric and electronic structure in
      various Pt(n) clusters is investigated using the ab initio self-consistent FEFF8
      code. Calculations based on FEFF8 are found to be in good agreement with
      experiment. For pure Pt clusters the XANES can distinguish between 2- and 3
      dimensional clusters. Self-consistency is important in determining the variation
      of XANES with cluster size. The effect of a support is also studied. In Pt-Cl(x)
      clusters the presence of a Cl-Pt bond leads to a "hybridization peak," i.e., a
      peak in the Cl d-density of states (d-DOS) mixed with Pt d-states. For Pt-H
      clusters hydrogen addition is well correlated with the growth of a broad shoulder
      on the white line. This change is attributed largely to AXAFS, i.e., to a
      corresponding change in the atomic background absorption.

PMID- 11512858
TI  - In situ XAFS analysis system for high-pressure catalytic reactions and its
      application to CO2 hydrogenation over a Rh/Y-zeolite catalyst.
AB  - An in-situ XAFS cell was developed and used for the structural analysis of a Rh
      ion-exchanged zeolite catalyst during high-pressure hydrogenation of carbon
      dioxide. The in-situ cell enabled analyses of the catalyst structures that
      changed with the reaction atmosphere and elapsed time; the peak assigned to Rh-O
      scattering changed to that assigned to Rh-Rh scattering at 404 K during the
      pretreatment by hydrogen. After 30 min. of the carbon dioxide hydrogenation
      reaction, the peak intensity assigned to Rh-Rh scattering increased corresponding
      to the increase in the catalytic activity.

PMID- 11512859
TI  - In situ EXAFS study on nickel metal particles dispersed on Loy Yang brown coal.
AB  - The structure of nickel catalysts supported on Loy Yang brown coal by an ion
      exchanging method during thermal treatment was studied by a XAFS technique. The
      exchanged nickel species aggregated to metal particles during pyrolysis and
      hydrogasification. The aggregation behaviour of nickel species depended on the
      amount of nickel loaded and/or treatment atmospheres.

PMID- 11512860
TI  - Characterization of silica-supported Ni catalysts effective for methane
      decomposition by Ni K-edge XAFS.
AB  - The structural change of Ni species during the methane decomposition into
      hydrogen and carbon over Ni/SiO2 catalyst was investigated by Ni K-edge
      XANES/EXAFS. Before the contact of methane with the Ni/SiO2 catalyst, Ni species
      were present as Ni metal mainly. The structure of the Ni metal did not change
      appreciably when the Ni/SiO2 was actively decomposing methane. In contrast, the
      formation of nickel carbide species was observed at the deactivation stage of the
      catalyst.

PMID- 11512861
TI  - Incorporation of Mn, Co and Zn cations into large-pore aluminophosphate molecular
      sieves MeAPO-50.
AB  - Large-pore metal modified aluminophosphate molecular sieves MeAPO-50
      (Me=Co,Zn,Mn) were synthesised by hydrothermal crystallisation using di-n
      propylamine as structure directing agent. EXAFS and XRD analysis show that
      cobalt(II), manganese(II) and zinc(II) are incorporated into the non-phosphorus
      tetrahedral framework sites of MeAPO-50 on the threefold-axis site, and on a site
      in a general position in the unit cell. Results of both methods on distribution
      of the metal over the two sites are compared.

PMID- 11512862
TI  - XANES study of Li-MgO and Li-La2O3-MgO catalysts for oxidative coupling of
      methane.
AB  - To characterize the defect sites in the near-surface and bulk phase of Li-MgO and
      Li-La2O3-MgO, XANES at Mg K-edge and La L3-edge was applied. For Li-MgO, it can
      be suggested that Li doping at a low content (2.5 wt%) brings about the formation
      of defect species only in the near-surface. This is due to the localization of
      doped Li ions in the surface, and thus the catalytically active species
      containing [Li+ O-] type center exist in the surface region. After OCM reaction,
      the detect species are formed in the near-surface over MgO and Li-MgO. By
      addition of La2O3 to Li-MgO (La/(Mg+La)=0.25), the structural change during the
      reaction is almost suppressed in the surface. In addition, the Li-La2O3-MgO shows
      higher C2 selectivity than Li-MgO.

PMID- 11512863
TI  - XAFS study of Mn-Ni/Al2O3 catalyst for carbon dioxide reforming of methane.
AB  - As an effective catalyst for carbon dioxide reforming of methane, manganese
      promoted Ni/Al2O3 catalyst was studied with XAFS. The catalysts after the
      reduction above 1073 K contained the metallic nickel, and several phases of
      manganese were shown by XANES and EXAFS. Results of EXAFS curve fitting indicated
      that the surface of large metallic nickel particles was partly covered with
      patches of MnO and metallic Mn. Radial structure function (RSF) of Mn K-edge
      showed the peaks due to Mn-Ni scattering without Mn-Mn scattering, indicating
      that the metallic manganese was attached to nickel in a highly dispersed state.
      Separate manganese phase was also formed without interaction with nickel.

PMID- 11512864
TI  - Co K-edge XAS study on a new cobalt-doped-SiO2 pillared clay.
AB  - New Co-doped-SiO2-sol pillared montmorillonite has been synthesized by interlayer
      hydrolysis and condensation of tetraethylorthosilicate (TEOS) in the presence of
      Co2+ ion using an organic template. The Co K-edge XANES and EXAFS analyses for
      the CoO-SiO2-PILC (before and after calcination) and for the references such as
      CoO and Co(OH)2 were performed in order to obtain electronic and local structural
      information of cobalt species, which may act as a catalytic active site for the
      selective reduction of NO(x), hydrodesulfurization, and Fischer-Tropsch reaction.
      According to the XANES spectra, the divalent cobalt ion is stabilized in an
      octahedral symmetry. The EXAFS result shows a significant change in local
      symmetry around cobalt ion upon calcination. The EXAFS fitting result before
      calcination shows that the cobalt species is in the form of hydroxide, with a
      small number of (Co-Co) pairs compared to the bulk Co(OH)2. After calcining at
      550 degrees C, the first nearest neighbours were fitted to six oxygen atoms with
      two different distances, and the second and the third neighbours were fitted to
      two Si and one Co atoms. It is, therefore, reasonable to suggest a structure
      model, where the cobalt species on the SiO2 sol exists as a nano cluster of
      Co(OH)2 before calcination but transforms to a nanosized cobalt oxide covalently
      bound to the surface of SiO2 pillar after calcination.

PMID- 11512865
TI  - Characterization of Ti-Beta zeolites and their reactivity for the photocatalytic
      reduction of CO2 with H2O.
AB  - A characterization of Ti-Beta zeolites synthesized under various conditions as
      well as an investigation of their photocatalytic properties for the reduction of
      CO2 with H2O at 323 K to produce CH4 and CH3OH were carried out. In situ XAFS
      spectra measurements indicated that a highly dispersed tetrahedral titanium oxide
      species was present in the zeolite framework and an increase in the coordination
      number of the titanium oxide species by the addition of H2O and CO2 molecules
      could be detected. The Ti-Beta zeolite having a hydrophilic property (Ti
      Beta(OH)) exhibited a more dramatic increase in the coordination number than the
      Ti-Beta(F) zeolite which had a hydrophobic property. These results suggest that
      CO2 and H2O molecules can be adsorbed efficiently onto the highly dispersed
      tetrahedrally coordinated titanium oxide species. UV irradiation of these Ti-Beta
      zeolite catalysts in the presence of H2O and CO2 led to the formation of CH4 and
      CH3OH. Ti-Beta(OH) exhibited a higher reactivity than Ti-Beta(F), while the
      selectivity for the formation of CH3OH on Ti-Beta(F) was higher than that for Ti
      Beta(OH). These results indicated that the reactivity and selectivity of the
      zeolite catalyst can be determined by the hydrophilic and hydrophobic properties
      of the zeolites.

PMID- 11512866
TI  - Site-selective XAFS spectroscopy tuned to surface active sites of Cu/ZnO and
      Cr/SiO2 catalysts.
AB  - XAFS (X-ray absorption fine structure) spectra were measured by using the
      fluorescence spectrometer for the emitted X-ray from sample. The chemical shifts
      between Cu0 and Cu1 and between CrIII and CrVI were evaluated. Tuning the
      fluorescence spectrometer to each energy, the Cu0 and CuI site-selective XANES
      for Cu/ZnO catalyst were measured. The first one was similar to the XANES of Cu
      metal and the second one was the 5 : 5 average of XANES for CuI sites + Cu metal.
      The population ratio of copper site of the Cu/ZnO catalyst was found to be Cu
      metal: Cu2O : CuI atomically dispersed on surface = 70(+/-23) : 22(+/-14) : 8(+/
      5). Site-selective XANES for CrIII site of Cr/SiO2 catalyst was also studied.

PMID- 11512867
TI  - Local structure of Pb(II) ion catalysts anchored within zeolite cavities and
      their photocatalytic reactivity for the elimination of N2O.
AB  - The Pb2+/ZSM-5 catalyst was prepared by an ion-exchange method and its
      photocatalytic activity for the decomposition of N2O under UV irradiation was
      investigated. In-situ UV-Vis absorption spectroscopy and XAFS (XANES and FT
      EXAFS) investigations revealed that the Pb2+ ions exist in a highly dispersed
      state within the pores of the zeolites. UV irradiation of the catalysts in the
      presence of N2O led to the photocatalytic decomposition of N2O into N2 at
      temperatures as low as 298K. The effective wavelength of the irradiated UV light
      indicated that the excited state of the Pb2+ ions included within the zeolite
      cavities plays a significant role in the photocatalytic decomposition of N2O
      molecules.

PMID- 11512868
TI  - Progress and challenges in the theory and interpretation of X-ray spectra.
AB  - There has been dramatic progress over the past decade both in theory and in ab
      initio calculations of X-ray absorption fine structure (XAFS). Rapid progress is
      now being made in understanding X-ray absorption near-edge structure (XANES).
      This presentation reviews the developments in this field by many groups leading
      up to the current state of the art. These developments have led to several ab
      initio codes, such as FEFF, which yield results comparable to experimental
      results for XAFS, and permit an interpretation of the spectra in terms of
      geometrical and electronic properties of a material. The review begins with a
      summary of the key theoretical developments that are essential for achieving a
      quantitative agreement with experiment for XAFS. The same high-order multiple
      scattering (MS) theory of XAFS can also give an approximate treatment of XANES,
      but this approach can fail close to an edge, where full MS calculations are often
      necessary. However, a fully quantitative treatment of XANES remains challenging,
      largely as a result of a number of many-body effects, e.g. the approximate
      treatment of the core-hole, multiplet effects, the photoelectron self energy and
      inelastic losses. Finally, natural extensions of the theory to other
      spectroscopies, such as anomalous X-ray scattering, DAFS (diffraction anomalous
      fine structure) and XMCD (X-ray magnetic circular dichroism) are briefly
      discussed. These developments are illustrated with a number of applications.

PMID- 11512869
TI  - Multi-component fitting XAFS analysis of molybdate species during catalyst
      preparation ration by the molten salt method.
AB  - The goal of the present study was to elucidate the formation mechanisms of highly
      dispersed catalysts by the molten salt method. For this purpose, multi-component
      fitting Mo K-edge EXAFS analysis was applied to the structure of molybdate
      catalysts prepared in KNO3 and NaNO3. The analysis revealed that MoO3 dissolved
      in molten salts was at first transformed into polymolybdate anions and finally
      into MoO(4)2- anions. The transformation into MoO(4)2- anions took place at a
      lower temperature when NaNO3 was used as molten salt than KNO3. In contrast,
      polymolybdate anions were stable even at higher temperature when ZrO2 was added
      as a support of molybdate.

PMID- 11512870
TI  - Investigations on the local structure of Ag+/ZSM-5 catalysts and their
      photocatalytic reactivities for the decomposition of N2O at 298 K.
AB  - Ag+/ZSM-5 catalysts were prepared by an ion-exchange method and UV-irradiation of
      the catalysts in the presence of N2O led to the photocatalytic decomposition of
      N2O into N2 and O2 at 298 K. Investigations on the effective wavelength of
      irradiated UV-light for the reaction as well as the in-situ characterization of
      the catalysts by means of XAFS, UV-Vis, photoluminescence and FT-IR
      spectroscopies revealed that the photoexcitation of the Ag+-N2O complexes formed
      between gaseous N2O and the isolated Ag+ ions play a significant role in this
      reaction.

PMID- 11512871
TI  - Local structure analyses of Ce0.5Zr0.5O2 mixed oxides by XAFS.
AB  - Three types of CeO2-ZrO2 with the same composition (Ce/Zr = 1) were prepared by
      different methods, exhibited the different oxygen storage/release capacity (OSC).
      To investigate the relationship between the OSC and the local structure, the Ce
      and Zr K-edges XAFS spectra for these samples were measured. The features of
      Fourier transforms of these samples were different from each other. This
      suggested that the OSC was remarkably exerted by the local structure around Ce
      and Zr. The quantitative curve-fitting analysis of EXAFS was applied, and it was
      concluded that homogeneous Ce(0.5)Zr(0.5)O2 solid solution at atomic level
      exhibited the highest OSC among these CeO2-ZrO2 with the same composition (Ce/Zr
      = 1).

PMID- 11512872
TI  - In situ studies on the structure of copper oxide/zinc oxide catalysts.
AB  - Cu/ZnO supported on alumina is a well-known catalyst for steam reforming of
      methanol. In this work it is attempted to assess the influence of elemental
      composition on the resulting active copper phase. XAFS measurements of calcined
      precursors were carried out at the Cu K edge and the Zn K edge. Corresponding RDF
      show that both copper oxide and zinc oxide exhibit considerable deviations from a
      linear dependence of their structure on the composition coinciding with changes
      in phase composition of hydroxycarbonate precursor. From time-resolved in situ
      experiments at the Cu K edge the degree of reduction can be monitored using a
      combination of factor analysis (PCA) and least-squares XANES fitting with
      suitable reference spectra (e.g. Cu metal, Cu2O, and CuO). It is shown that Cu2O
      forms prior to Cu. The extent of reduction to Cu exhibited a typical nucleation
      growth behavior with an enhanced reaction rate for more diluted samples. Adding
      oxygen to the feed gas leads to the formation of mixed Cu2+ and Cu+ phases
      accompanied by a complete loss of activity in methanol steam reforming. After
      switching back to steam reforming conditions the activity is regained.

PMID- 11512873
TI  - Effect of Si(IV) substitution on the stability of microporous ZnAPSO-44 solid
      acid catalysts: a combined XAS/XRD study.
AB  - The combined XAS/XRD technique has been used to investigate the stability of the
      microporous structure during calcination process for a series of ZnAPSO-44
      materials. Incorporation of large amounts of Zn is found to produce materials
      that are unstable upon removal of the structure directing organic template
      molecule. However, simultaneous incorporation of Si is found to increase the
      thermal stability of the materials, yielding catalysts that are well suited for
      acid catalysed reactions.

PMID- 11512874
TI  - The architecture of Mg(II) centres in MAPO-36 solid acid catalysts.
AB  - The local structure around Mg2+ ions of a Magnesium substituted aluminophosphate,
      with the ATS structure (MgAPO-36, Mg/P=0.08), in the as-prepared and calcined
      state has been investigated by Mg K-edge XAS spectroscopy. High quality XAS data
      were collected using the solid-state fluorescence detector. Mg2+ is found to
      replace tetrahedrally co-ordinated Al3+ in the as-prepared state and remained
      intact even after calcination, thus yielding a highly active, solid acid
      catalyst.

PMID- 11512875
TI  - DXAFS study on the decarbonylation process of Mo(CO)6 in NaY supercages.
AB  - The decarbonylation process of Mo(CO)6 in the NaY supercages was studied by means
      of a time resolved dispersive XAFS method during temperature programmed
      decarbonylation. XANES analysis demonstrated that the decarbonylation proceeded
      through two steps and that a stable intermediate existed between 440-490 K. The
      curve fitting analysis revealed that the intermediate was a molybdenum monomer
      subcarbonyl species coordinated by three CO ligands and three oxygen atoms of
      zeolite framework. Molybdenum dimer subcarbonyl species were not observed. This
      study demonstrated that DXAFS technique is a powerful method to study the dynamic
      behaviour of the Mo carbonyl species during decarbonylation process.

PMID- 11512876
TI  - In situ and ex situ XANES study of nanodispersed Mo species in zeolites used in
      fine chemistry catalysis.
AB  - Mo K-edge XANES experiments on Mo-containing zeolites at low Mo loading (1 and 2
      wt% of Mo on H-ZSM-11, H-BETA and H-ZSM-5 catalysts), active in fine chemistry
      reactions, were performed ex situ as function of sample calcination temperature
      in air (in the range 773-973 K) or in situ at 873 and 973K under N2 flow. The
      results showed a 4-fold oxygen coordination for the incorporated Mo species in
      the activated (dehydrated) state. Combining these results with additional data
      evidences an almost total Mo exchange inside the zeolite channels.

PMID- 11512877
TI  - Structural analysis of La/Al2O3 catalysts by La K-edge XAFS.
AB  - Structural analysis of La/Al2O3 catalyst materials was carried out by means of
      XRD and La K-edge XAFS. Influences of loading amounts and treatment temperature
      on the local structure around La were investigated. La atoms are supported on
      gamma-Al2O3 in a highly dispersed form when a loading amount is less than 0.2
      mmol g(Al2O3)(-1), and structural transformation of the La species does not take
      place in the temperature ranges of 873-1273 K. La species of highly loaded
      catalysts start to change their structure from oxide-like form to the aluminate
      at 1073 K. Formation of LaAlO3 perovskite on the catalyst surface requires a
      concentration of La atoms above 0.5 mmol g(Al2O3)(-1) (7.5 wt% as La2O3).

PMID- 11512878
TI  - XAFS studies on the local structures of Ti-HMS mesoporous molecular sieves and
      their photocatalytic properties.
AB  - Various Ti-containing HMS mesoporous molecular sieves having high surface areas
      and pore volumes have been prepared at ambient temperature. The Ti-HMS samples
      exhibited a well-defined XRD pattern of typical hexagonal lattice. UV-vis and
      XAFS spectral for the calcined forms of Ti-HMS indicated that the Ti ions are
      tetrahedrally coordinated in the framework of HMS for the samples of Ti-HMS(1)
      and Ti-HMS(2), while at least a fraction of Ti-oxides in Ti-HMS(10) is in
      octahedral coordination. UV irradiation of the Ti-HMS catalysts in the presence
      of NO was found to lead to the decomposition of NO to form N2, O2, and N2O at 273
      K with different yields and product distributions. The photocatalytic performance
      of Ti-oxides appears to be completely modified by their incorporation structure
      and reaction environment. High efficiency and selectivity for the formation of N2
      and O2 in the photocatalytic decomposition of NO was achieved with the Ti-HMS(1)
      having highly dispersed isolated tetrahedral titanium oxide species, while the
      reactivity decreased with an increase in the Ti content.

PMID- 11512879
TI  - Characterization and photocatalytic reduction of CO2 with H2O on Ti/FSM-16
      synthesized by various preparation methods.
AB  - Ti/FSM-16 photocatalysts were prepared by various methods and their reactivity
      for the photocatalytic reduction of CO2 with H2O at 323 K was investigated. UV
      irradiation of Ti/FSM-16 in the presence of CO2 and H2O led to the formation of
      CH4 and CH3OH. The photocatalytic reactivity and selectivity differed remarkably
      by variations in the preparation method. Analyses of the UV-Vis absorption and
      XAFS spectra showed that the dispersion and local structure of the Ti-oxide
      species greatly depended on the preparation method. The formation of CH3OH was
      found to be related to the local structure of the Ti-oxide species while the
      yield of the photoluminescence was attributed to the charge transfer excited
      state of the highly dispersed tetrahedrally coordinated Ti-oxide species.
      Methanol formation was found to be more efficient on Ti/FSM-16 having such highly
      dispersed tetrahedrally coordinated Ti-oxide species.

PMID- 11512880
TI  - Preparation of Ti-Si binary oxide thin film photocatalysts by the application of
      an ionized cluster beam method.
AB  - Ti-Si binary oxide thin films with various Ti contents were prepared in a dry
      process by using an Ionized Cluster Beam (ICB) deposition method with multi ion
      sources. From the results of UV-VIS measurements, the transmittance of these
      binary oxide thin films is very high compared to pure TiO2 thin films, indicating
      that the Ti-oxide exists in a highly dispersed state in the SiO2 matrices. The
      EXAFS spectra of these thin films with lower Ti content exhibited only a sharp
      preedge peak attributed to the highly dispersed Ti-oxide species which differs
      from the peaks of anatase TiO2 thin films. UV light irradiation of these Ti-Si
      binary oxide thin films in the presence of NO were found to lead to the evolution
      of N2 and O2 with a good linearity against the irradiation time. The lower the Ti
      content, the higher the reactivity and the selectivity for the formation of N2
      were. These results clearly indicate that the highly dispersed Ti-oxide species
      plays an important role in the formation of N2 and O2 for the photocatalytic
      decomposition of NO under UV light irradiation.

PMID- 11512881
TI  - Characterization of the active site structure of Pd and Pd-promoted Mo sulfide
      catalysts by means of XAFS.
AB  - Recently, noble metal catalysts are noted as promising candidates for new super
      deep-hydrodesulfurization (HDS) catalysts. In this study, we investigated the
      structure of Pd particles supported on zeolite and Al2O3 under a sulfidation or
      reduction condition. From EXAFS analysis, it was found for sulfided Pd catalysts
      that small Pd sulfide clusters are formed without sintering. It was also revealed
      that no extensive growth of metal Pd particles occurs in Pd/NaY sulfide catalysts
      even after a treatment with H2 at 673 K. The dispersion of Pd metal particles is
      improved by H2/H2S treatment. These results indicate that in the presence of H2S,
      Pd shows high resistance against particle growth. A comparison of the Mo and Pd K
      edge EXAFS spectra for MoS(x)/Pd-NaY and Pd-NaY catalysts revealed the existence
      of Mo-Pd bondings by the addition of Mo sulfide, indicating a direct interaction
      between Mo and Pd sulfides.

PMID- 11512882
TI  - Structural characterization of W-Ni-Al2O3 catalysts.
AB  - A series of W/Ni/Al2O3 catalysts was prepared by coprecipitation of nickel and
      aluminum and impregnation of tungsten. The samples were characterized by XRD, XPS
      and XAS techniques. XRD measurements detected two phases: NiO as the main phase
      and NiAl2O4 in lower amount; no phase containing tungsten was detected. XPS
      measurements indicated the presence of Al2O3, NiAl2O4, and Al2(WO4)3 phases on
      the catalyst surfaces. The XANES spectra of catalysts were rather similar for all
      of the samples. According to the EXAFS results, at the short range level,
      tungsten does not form any bound with Ni atoms. The nickel first coordination
      shell in the catalysts containing tungsten is similar to that encountered in COP
      1 catalyst without tungsten. The lower Ni-Ni coordination number observed for all
      catalysts, when compared to the NiO phase, can be attributed to the nickel
      aluminum interaction.

PMID- 11512883
TI  - XAFS study on the sulfidation mechanisms of Co-Mo catalysts supported on
      activated carbon and alumina: effect of complexing agent.
AB  - The effect of nitrilotriacetic acid (NTA) as a complexing agent on the
      sulfidation mechanisms of Co-Mo catalysts supported on activated carbon and
      alumina was examined by the XAFS technique. The XAFS results revealed that NTA
      interacted with Co atoms and formed the Co-NTA interaction, while it showed
      almost no influence on the local structures around Mo atoms. The Co-NTA
      interaction suppressed the aggregation of cobalt atoms and the interaction
      between cobalt and alumina during sulfiding, and consequently promoted the
      formation of the Co-Mo-S phase.

PMID- 11512884
TI  - Time-resolved energy-dispersive XAFS study on the reduction process of Cu-ZSM-5
      catalysts.
AB  - The time-resolved reduction process of copper cations in ZSM-5 during temperature
      programmed reduction (300-700 K) was studied by energy dispersive X-ray
      absorption fine structure (DXAFS). The Cu K-edge DXAFS spectra for isolated Cu2+
      species in the channels of ZSM-5 were recorded at an interval of 1 s during the
      reduction. The curve fitting analysis of the EXAFS data and the XANES analysis
      revealed that the isolated Cu2+ species in the channels were reduced stepwise.
      They were reduced to isolated Cu+ species at 400-450 K and the Cu+ species to Cu0
      metallic clusters at 550-650 K. Small clusters like Cu4 were initially formed,
      followed by particle growth. A small part of them went out to the outer surfaces
      of ZSM-5 during the reduction.

PMID- 11512885
TI  - Hydration of some large and highly charged metal ions.
AB  - EXAFS studies of metal ions with hydration numbers higher than six in aqueous
      solution, often show asymmetric distribution of the metal-oxygen bond distances.
      The hydration number can be determined from a correlation with the bond distance.
      The mean Ca-O distance 2.46(1) A shows the calcium(II) ion to be eight-hydrated
      in a wide asymmetric distribution. Theoretically calculated EXAFS oscillations
      for individual snapshots from an MD simulation show large variations. The
      scandium(III) ion is surrounded by two groups of about eight water molecules,
      with the mean Sc-O distance 2.185(6) A. The yttrium(III) ion coordinates eight
      waters in an asymmetric distribution at 2.368(5) A, and the lanthanum(III) ion 6
      + 3 water molecules at 2.52(2) and 2.65(3) A, respectively. For the the
      uranium(IV) and thorium(IV) ions, the M-O distances 2.42(1) and 2.45(1) A,
      respectively, indicate hydration numbers close to 10.

PMID- 11512886
TI  - Soft X-ray spectromicroscopy of polymers and bipolymer interfaces.
AB  - The status of soft X-ray spectromicroscopy (near edge X-ray absorption, or
      NEXAFS, microscopy) is summarized, with particular emphasis on recent
      collaborative studies carried out by the author's group at the scanning
      transmission X-ray microscopy (STXM) and the photoelectron emission microscopy
      (PEEM) instruments at the Advanced Light Source. Results described include:
      characterization of phase segregation and filler particles in polyurethanes;
      effects of confinement on polymer self-organization; characterization of
      chemically structured polyurea capsule walls; and preferential interactions of
      proteins with chemically heterogeneous polymer surfaces. The latter is part of a
      systematic study of the biocompatibility of polymers used in blood contact
      applications.

PMID- 11512887
TI  - A study of uranium speciation in acetate solutions at temperatures from 25 to 250
      degrees C.
AB  - We report U L3-edge XAS analysis results from a study of the speciation of U(VI)
      in acetate solutions between 25 and 250 degrees C, at pH's between 1.82 and 2.57
      and [acetate]:[U] ratios of 0.5 to 50. At 25 degrees C in excess acetate there
      are at least two acetate ligands in the equatorial plane with a U-O bond distance
      of 2.44 A. At elevated temperatures with excess acetate, acetate is still
      coordinated but the speciation mixture appears more complicated. Less evidence
      exists for acetate coordination when [acetate]:[U] ratio is unity or below. pH
      within this limited range appears to have little effect on the uranyl speciation.

PMID- 11512888
TI  - EXAFS studies of americium (III)-benzimidazole complex in ethanol.
AB  - The local structures of Am, Nd and Er-Benzimidazole (Biz) in solution were
      determined by EXAFS. The BIZ molecule coordinated to Am and Nd through two
      nitrogen atoms in a bidentate fashion. Two nitrogen atoms of BIZ ligated to Am
      and Nd with the bond distances R(Am-n) N=2.63A and R(Nd-N) = 2.65 A,
      respectively. The total coordination number of the Am BIZ complexes (at a molar
      ratio of metal ion to ligand of 1:20) was approximately 10 but that of Nd BIZ
      complex was approximately 9.

PMID- 11512889
TI  - K- and L-edge XAFS determination of the local structure of aqueous Nd(III) and
      Eu(III).
AB  - The short-range coordination of Nd(III) and Eu(III) ions in aqueous solutions has
      been investigated by means of K-edge x-ray absorption spectroscopy. Experimental
      data are presented which demonstrate that an accurate determination of the
      Nd(III) and Eu(III) hydration structural parameters can be obtained from the
      analysis of the K-edge spectra. It is shown that the large widths of the core
      hole states do not appreciably reduce the potential structural information of the
      K-edge EXAFS data. In addition the available k-range of the K-edge spectra is
      much wider compared to that of the L3-edge which is affected by the presence of
      double-electron excitations in a more severe fashion.

PMID- 11512890
TI  - A study of the coordination environment in aqueous cadmium-thiol complexes by
      EXAFS spectroscopy: experimental vs. theoretical standards.
AB  - Using EXAFS, we investigated the changes in the local structure of Cd(II)
      complexes formed with a series of low-molecular-weight thiols at different
      thiol/cadmium stoichiometries. For dilute solutions, a comparison of theoretical
      and experimental standards proved the latter approach superior. The number of
      bound oxygen atoms decreased while the number of sulfur atoms increased as the
      thiol/cadmium ratios increased, indicating that up to four thiol compounds can
      bind to cadmium in aqueous solutions. The computer code FEFFIT was modified to
      employ experimental and theoretical standards with equal facility.

PMID- 11512891
TI  - Structural studies of lanthanide (III) complexes with oxydiacetic acid and
      iminodiacetic acid in aqueous solution by EXAFS.
AB  - The local structure of the trivalent lanthanide (Ln(III)) complexes with
      oxydiacetic acid (ODA) and iminodiacetic acid (IDA) in aqueous solution was
      investigated by EXAFS spectroscopy. The coordination number and the bond distance
      were obtained by the detailed EXAFS analysis. The coordination number of Ln(III)
      in both the Ln-ODA and -IDA systems decreases from nine for lighter Ln(III) to
      eight for heavier Ln(III). The bond distances of ether O atoms from Ln(III) in
      the Ln(ODA)(3)3- complexes are shorter than those of N atoms in the Ln(IDA)(3)3-
      ones.

PMID- 11512892
TI  - XAFS analysis of triiodide ion in solutions.
AB  - Iodine K-edge XAFS of triiodide ions in various solvents were measured at SPring
      8 BL01B1 and analyzed. Though the anion takes a linear and symmetric form, the
      second peak expected from enhanced multiple scatterings can be hardly observed
      because of its large vibrations. The bond distances and the Debye-Waller factors
      for the I-I couple vary when protic solvents were used and they were similar when
      aprotic solvents were used. It was indicated that the larger the Mayers' acceptor
      number of the solvent is, the larger the Debye-Waller factor is. It was also
      found that among the aprotic solvents, the larger the Gutmann's donor number is,
      the smaller the Debye-Waller factor is.

PMID- 11512893
TI  - Phase formation during the decomposition of ammonium heptamolybdate--an in situ
      XAFS and XRD investigation.
AB  - The decomposition of ammonium heptamolybdate was investigated by in situ XAFS and
      in situ XRD to elucidate the influence of different atmospheres on the products
      formed the formation of different decomposition products and various
      intermediates is described in detail.

PMID- 11512894
TI  - Determination of dissociation energy for ligand exchange reaction from EXAFS.
AB  - EXAFS (extended X-ray absorption fine structure) experiments were performed at
      several different temperatures for a series of 3d transition metal ions (Cr3+,
      Fe3+, Fe2+, Ni2+, Co2+, Zn2+) in aqueous solutions. Anharmonic EXAFS analyses,
      which include up to third order cumulant, were carried out to study on the metal
      oxygen bonding potential. According to the model in which the dissociation
      process is dominant for the ligand-water exchange reaction, the dissociation
      energy has been first evaluated from EXAFS in solution phase.

PMID- 11512895
TI  - Solid-state kinetics from time-resolved in situ XAFS investigations: reduction
      and oxidation of molybdenum oxides.
AB  - The reduction of MoO3 with hydrogen was studied by in situ X-ray absorption
      spectroscopy. The experiments performed focused on elucidating phase composition
      and evolution with time under isothermal reduction conditions. From temperature
      programmed experiments short-range structural details about the early stage of
      the reduction were obtained.

PMID- 11512896
TI  - Zirconium speciation in lactate solutions and polyacrylate gels.
AB  - Controlling gelation kinetics is an important objective for several applications
      (ceramic and thin film syntheses, reduction in permeability of porous rock, etc).
      There is a growing interest in studying the gelation of polymers by zirconium, a
      crosslinker of lower toxicity than the chromium which is still commonly used. XAS
      at the Zr K-edge was performed at the European Synchrotron Radiation Facility
      (ESRF) on the BM32 beamline. The fluorescence detection was used to carry out
      successful in situ speciation at concentrations as low as 36 ppm. The Zr
      speciation was determined both in ZrLa (where La stands for lactate) aqueous
      solutions and in gels of a terpolymer of acrylamide having 2% of zirconium
      reactive acrylate side groups and 2% of sulfonate groups introduced to prevent
      syneresis. XANES results show that Zr is always in a dodecahedral geometry. In
      ZrLa solutions. EXAFS results indicate that Zr species grow from a dimer Zr2(La)6
      to a tetramer (Zr4(La)x) and then to larger polymers resulting from tetramer
      associations, as the Zr concentration decreases from 51840 ppm to 36ppm. In
      polymer gels, Zr species appear to be dimers at pH 6 while tetramers are found
      when gelation occurred at pH 7. Calculations taking into account multiple
      scattering effects as well as dynamic molecular calculation confirmed conclusions
      derived from conventional EXAFS analysis.

PMID- 11512897
TI  - Characterization of ruthenium-dinitrogen tetraamine complexes by XAFS
      spectroscopy.
AB  - A reaction between N2 and trans-Ru(II)Cl2L (L=2,5,9,12-tetramethyl-2.5,9,12
      tetraazatridecane) in aqueous solutions has been investigated by XAFS
      spectroscopy. Ru K-edge EXAFS clearly revealed that there exists an N2-bridged
      binuclear complex and that the Ru-Ru distance is 4.96 A with the coordination
      number of 0.5. The Ru K-edge energies of the N2 complexes are closer to that of
      Ru(III)Cl2L+ rather than that of Ru(II)Cl2L, indicating back donation from the Ru
      dpi to the N2 pi* orbitals.

PMID- 11512898
TI  - Determination of metal-metal distances: significance and accuracy.
AB  - Nature utilises a variety of metal clusters as catalytic centers. Some of them
      make use of two or more metals in the catalytic site. The variation of metal
      metal distances plays an important role in several processes like charge transfer
      and weakening of bonds. X-ray absorption spectroscopy can determine these metal
      metal distances in several states (crystal, solution or amorphous). However
      sometimes backscattering from light elements hides the metal-metal contribution
      to the fine structure. Here we point out significance and accuracy of metal-metal
      distances in a model system. Therefore a number of different refinement protocols
      are applied to the data. These protocols will be discussed focusing on the
      significance and accuracy of the metal-metal distances extracted from the data.

PMID- 11512899
TI  - EXAFS as a tool for bond-length determination in the environment of heavy atoms.
AB  - Single crystal X-ray diffraction measurements are complicated in the presence of
      heavy atoms. In these cases the structure factors are mainly influenced by the
      heavy scatterers and the error in determination of atomic coordinates increases
      for light atoms. The difficulties grow if the unit cell dimensions or the space
      group symmetry remain uncertain. If the structure model is similar to the correct
      structure, it is difficult to find an independent criterion for the accuracy of
      the bond-length determination. We demonstrate that extended X-ray absorption fine
      structure (EXAFS) spectroscopy is a useful tool for the investigation of local
      bond lengths in the environment of heavy atoms.

PMID- 11512900
TI  - XAFS investigations of tin nitrides.
AB  - Tin nitrides (Sn3N4) prepared by the reaction of Sn-halides with KNH2 in liquid
      ammonia and a subsequent vacuum annealing procedure were investigated with
      transmission mode XAFS experiments. While the near edge data suggest the presence
      of a univalent Sn-compound with a valency close to +4, the analysis of the
      extended X-ray absorption fine structure proves the presence of two different
      local Sn sites in this crystal structure: While Sn(1) is surrounded by 4 nitrogen
      in a distance of 2.06 A, each Sn(2) ion is coordinated with 6 nitrogen at about
      2.17 A radial distance.

PMID- 11512901
TI  - EXAFS and thermodynamics of Fe(II) spin transition polymeric compounds.
AB  - We have studied the temperature variations of the EXAFS spectra of three
      Fe(II)/triazole-based spin transition polymeric compounds compared to a monomer
      belonging to the same family. These compounds have various temperatures of
      transition and hysteresis loop widths. In the three polymers, the Fe-Fe-Fe
      alignment, detected by a multiple scattering signal at the double Fe-Fe distance,
      is preserved through the spin transition. For the four compounds, we have studied
      the variations versus temperature of the Debye-Waller factors for both FeN6
      (first shell) and Fe-Fe-Fe (multiple scattering path, only for the polymers). We
      report a strong increase of (sigma2(FeN6) through the spin transition for the
      monomer and two of the polymeric species. For the polymers an increase of
      sigma2(Fe-Fe-Fe) is also observed. These observations confirm the results
      available in the literature, and we confirm the interpretation as an increase of
      the vibrational part of the DW. For one particular polymer, we observe an
      unexpected behaviour: no significant increase of the Debye-Waller factor from low
      spin to high spin states. The EXAFS study of these non mono-crystalline species
      is the only way to discuss the local structure-thermodynamics properties
      relationships, and particularly the so-called cooperative effect in the spin
      transition process.

PMID- 11512902
TI  - XANES study on Ruddlesden-Popper phase, La(n+1)Ni(n)O(3n+1) (n=1,2 and infinity).
AB  - Ruddlesden-Popper phase, La(n+1)Ni(n)O(3n+1 (n=1, 2, and infinity) compounds were
      prepared by citrate sol-gel method. We revealed the origin of the variation of
      the electrical conductivities in La(n+1)Ni(n)O(3n+1 (n=1, 2, and infinity) using
      resistivity measurements, Rietveld analysis, and X-ray absorption spectroscopy.
      According to the XANES spectra, it is found that the degree of 4p(pi) - 4psigma
      energy splitting between 8345 eV and 8350 eV is qualitatively proportional to the
      elongation of the out-of-plane Ni-O bond length. With the decrease of 4p(pi) -
      4psigma splitting, the strong hybridization of the sigma-bonding between Ni-3d
      and O-2p orbitals creates narrow antibonding sigma* bands, which finally results
      in the lower electrical resistivity.

PMID- 11512903
TI  - Thermal decomposition of (NH4)2[PdCl6] studied by in situ X-ray absorption
      spectroscopy.
AB  - In situ X-ray absorption near edge structure (XANES) investigations were carried
      out at chlorine K edge and palladium L3 edge to study the mechanism of the
      thermal decomposition of ammonium hexachloropalladate. The spectra show a
      characteristic feature for the initial step that might be explained as the
      formation of the precursor via ligand exchange (Cl --> NH3). Multiple scattering
      calculations (Feff 8) for the Cl K, Pd and Rh L3 edges were successful in
      simulating the XANES spectra of the precursor as well as the reference compounds
      (NH4)2 [PdCl4] and (NH4)3[RhCl6].

PMID- 11512904
TI  - XAFS studies of Tb or Eu cored dendrimer complexes with various properties of
      luminescence.
AB  - We studied the extended X-ray absorption fine structure (EXAFS) of Tb or Eu L3
      edge of Tb(III) or Eu(III)-cored complexes of different luminescence to which
      different poly(benzyl ether) dendrons coordinated. The complexes were prepared
      via a ligand exchange reaction of dendritic carboxylic acid and acetate. Results
      show that (a) the Eu complex of the first generation of the 3,4- or 3,5
      dibenzyloxyphenyl type had a coordination structure different from that of the
      2,4-dibenzyloxyphenyl type; (b) the Eu complex of the first generation of 3,5
      dinaphthylmethoxyphenyl type had a Eu-O coordination number higher than the total
      number of oxygen atoms in the carboxylate groups; (c) the Tb complex of the bulky
      fourth generation had a Th-O coordination number higher than that of the first
      generation. These results show that the different poly(benzyl ether) dendrons
      cause the different coordination, which might differently influence the
      luminescence properties of the complexes.

PMID- 11512905
TI  - X-ray absorption near edge studies of some binuclear copper(II) complexes.
AB  - X-ray K-absorption near edge studies have been carried out on the binuclear
      copper (II) dithiocarbamate (dtc) complexes having the following general
      structure: [structure in text] where R = me (methyl); et (ethyl); npr (normal
      propyl); chx (cyclohexane) It has been found that the chemical shift values are
      higher in the chlorine adducts as compared to the values of chemical shift
      reported by us in an earlier work for the parent complexes, showing that the
      chlorine adducts are more ionic. The observed splitting of the principal
      absorption maximum (1s-4p) in the chlorine adducts has been explained in terms of
      the splitting of the metal 4p orbital degeneracy.

PMID- 11512906
TI  - Carboplatin and oxaliplatin decomposition in chloride medium, monitored by XAS.
AB  - The stability of carboplatin and oxaliplatin aqueous solutions has been studied
      under different chloride ions concentration and pH conditions. For both
      compounds, we demonstrate the chloration of the platinum first coordination
      shell.

PMID- 11512907
TI  - NEXAFS multiple scattering calculations of KO2.
AB  - Since many years the oxidation of alkali metals has being attracted much interest
      due to the catalytic properties of metal promoters and the simple electronic
      structure of alkali atoms. The alkali-oxides phase diagram indicates that the
      interaction of oxygen with alkali metals can lead to the formation of different
      atomic O2- ions and molecular O2(-) and O(2)2- ions. Potassium superoxide has
      been prepared in situ and high resolution O k-edge absorption NEXAFS spectra have
      been measured at the VUV beam-line at ELETTRA facility. The experimental data
      have been analyzed by multiple scattering approach deriving many geometrical and
      electronic details. In particular, we have found that the growth material
      structure is of the KO2 type with an O-O distance of about 1.35A and that the
      transition involving single pi molecular empty state of the superoxide O2(-)
      anion has a fine structure. Multiple Scattering self consistent calculation
      indicates that the bond between oxygen anion and K atom is totally ionic and that
      the fine structure is essentially due to solid state effects.

PMID- 11512908
TI  - Prospects for X-ray absorption with the super-bright light sources of the future.
AB  - The immense growth in applications of X-ray absorption spectroscopy (XAS) has
      been enabled by the widespread availability of intense tunable X-rays from
      synchrotron radiation sources. Recently, new concepts have been proposed for
      fourth-generation light sources, such as the SASE (self-amplified stimulated
      emission) X-ray free-electron lasers (XFELs) being pursued at Hamburg (TESLA) and
      Stanford (LCLS), and the recirculator ring (MARS) at Novosibirsk. These sources
      offer expected gains of many orders of magnitude in instantaneous brilliance,
      which will unlock opportunities for qualitatively different science. Examples of
      new or greatly expanded techniques in XAS could include Raman X-ray absorption
      fine structure (XAFS), pump-probe experiments, time-resolved XAFS and small-spot
      X-ray spectromicroscopy, although the limited tunability of the sources might not
      allow conventional XAFS measurements. Multi-photon X-ray absorption could become
      a new field of study. There should not be a collective stampede to these new
      sources, however, and it is likely that storage rings will continue to be
      necessary for most XAFS applications. The extreme brightness of these future
      light sources will present difficult challenges in instrumentation, especially
      detectors and sample containment. Practitioners will also have to exercise
      caution, because the intensity of the beam will surely destroy many samples and
      in some cases there will be so many photons absorbed per atom that XAFS will be
      impossible.

PMID- 11512909
TI  - 4d Electronic structure analysis of ruthenium in the perovskite oxides by Ru K-
      and L-edge XAS.
AB  - The 4d electronic structure of ruthenium in the perovskite oxides, La2MRuIVO6 (M
      = Zn, Mg, and Li) and Ba2YRuVO6, has been investigated by the Ru K-and L-edge
      XANES and EXAFS analyses. Such X-ray absorption spectroscopic results clarify
      that the RuIV (d4) and RuV (d3) ions are stabilized in nearly regular Oh site.
      Comparing the Ru L-edge XANES spectra of perovskites containing isovalent
      ruthenium, it has been found that the t2g state is mainly influenced by A site
      cation, whereas the eg is mainly affected by neighboring B site cation. The
      experimental EXAFS spectra in the range of R < or = approximately 4.5 A are well
      reproduced by ab-initio calculation based on crystallographic data, which
      supports the long-range structure presented by Rietveld refinement.

PMID- 11512910
TI  - XAFS study on a pressure-induced superconductor Cs3C60 under high pressure.
AB  - Cs K-edge XAFS of Cs3C60 which is a pressure-induced superconductor were measured
      at 21 and 34 kbar by using a diamond anvil cell (DAC) in order to obtain the
      structural information under high pressure, and to clarify the origin of the
      pressure-induced superconductivity. The distances and the mean square
      displacements between the Cs and C atoms are consistent with those determined by
      X-ray powder diffraction. Consequently, the high-pressure XAFS can give the
      reliable structural-information on a fullerene superconductor under high
      pressure. We also show the procedure of the analysis of high-pressure XAFS with
      DAC in detail.

PMID- 11512911
TI  - Local structure analysis of Ti species stabilized in ion exchangeable layer
      solids by x-ray absorption spectroscopy.
AB  - Nano-sized titanium dioxides are incorporated into the interlayer spaces of ion
      exchangeable layered perovskites, H(1-x)Ca2(x)La(x)Nb3O10 (x=0.0-0.75), by
      replacing the interlayer protons with positively charged TiO2 nano-sol particles
      or basic titanium glycolate complex (titanatrane). Powder X-ray diffraction
      analysis. UV-Vis absorption spectroscopy, thermogravimetric analysis, and N2
      adsorption-desorption isotherm measurements show that quantum sized TiO2
      particles are stabilized in between perovskite lattices to form micropores
      (S(BET) = 37-110 m2/g). X-ray absorption spectroscopy at the Ti K-edge was used
      for investigating the local environment around Ti atoms constituting the
      interlayer pillars. According to the XANES spectra, the 'as-pillared' Ti species
      have the same local environments with those of precursory species, which
      subsequently converted into TiO2 clusters with rutile and anatase-like local
      structures when TiO2 nano-sol particles and titanatrane are used as pillaring
      species. respectively. It is also found that the local environment of TiO2
      remains almost constant irrespective of the layer charge density, while the TiO2
      pillar content and the microporosity increase with the latter.

PMID- 11512912
TI  - Ion exchange and fixation of rare-earth cation into expandable tetrasilicic
      fluorine mica.
AB  - Rare-earth cation (Nd3+) are incorporated into the interlayer spaces between the
      silicate layers of synthetic fluorine mica, Na0.665Mg2.68(Si3.98)Al0.02F1.98, by
      conventional ion exchange reaction. Subsequent migration of the interlayer
      cations upon calcination into the vacant octahedra of 2:1 layers is followed by
      powder X-ray diffraction, diffuse-reflectance UV spectroscopy, and X-ray
      absorption spectroscopy as a function of calcination temperature. It is found
      from the spectroscopic analyses that the interlayer cations start to migrate into
      the octahedral vacant sites from 400 degrees C through the hexagonal siloxane
      ring of the tetrahedral silicate layers. According to the Nd L(III)-edge XANES
      spectra, the normalized absorption intensity gradually decreases while the FWHM
      increases with temperature, suggesting that the bonding character of rare-earth
      cations and silicate lattices evolves from ionic to covalent as the calcination
      temperature increases.

PMID- 11512913
TI  - XAFS study of copper species stabilized in the interlayer space of layered
      perovskite oxides.
AB  - New intercalation compounds with Cu2+ ions in the interlayer of layered
      perovskite oxides, OA(1-x)Ca(2-x)La(x)Nb3O10) (OA = n-octylammonium ion, 0 < or =
      x < 1), have been prepared by ion-exchange reaction, and characterized by means
      of XRD and XAS. For the detail elucidation of the fine structure of the Cu K-edge
      XANES spectra, polarized XAS was applied for the [Cu(en)2]2+ and Cu2+ ions
      intercalated to the single crystal. According to the XANES and EXAFS spectra
      measured at Cu K-edge, copper ions are four coordinated. In addition, XANES
      spectra have shown that the charge transfer from host layer to intercalated ions
      influences on the chemical state of copper ion.

PMID- 11512914
TI  - Iodine L-edge XAFS study of linear polyiodide chains in amylose and alpha
      cyclodextrin.
AB  - We performed iodine L edge XAFS measurements on blue-black amylose-iodine complex
      to obtain information about the electronic and geometrical structures of
      polyiodide chain included in amylose helix. Measurements were also carried out on
      crystalline alpha-cyclodextrin-iodine complex (alpha-cyclodextrin)2 x Cd0.5 x I5
      x 27H2O, in which the polyiodide chain is known to consist of I(5)- unit. It was
      found that the XANES spectra of these complexes have similar line shapes except
      for some minor differences, indicating that there are close similarities in the
      nature of polyiodide chains in these complexes. Besides their similarity,
      difference in the intensity of the peak at the L1 absorption edge was observed.
      Its implication for the electronic and geometrical structures is also discussed.

PMID- 11512915
TI  - Study on local structure around Ce and Gd atoms in CeO2-Gd2O3 binary system.
AB  - X-ray absorption spectra near Ce and Gd K-edges of binary oxide of Ce(x)Gd(1
      x)O(3+x)/2 (0 < or = x < or = 0.5) in C-type structure solid solution were
      measured by use of the beamline BL01B1 at SPring-8. Interatomic distances between
      rare-earth and oxygen atoms. R(Gd-O) and R(Ce-O), were evaluated with the
      extended x-ray absorption fine structure analysis and found to increase with x.
      R(Gd-O) was larger than R(Ce-O) by about 0.1 A. Metal-oxygen distances estimated
      as their linear combinations, xR(Ce-O) + (1-x)R(Gd-O), well agreed with those
      determined by X-ray diffraction.

PMID- 11512916
TI  - In situ EXAFS study on the formation of smectite-type clays containing cobalt
      cations in lattice.
AB  - Smectite-type clays containing cobalt cations in octahedral sheets (MST (Co))
      were prepared by a hydrothermal treatment of a water slurry of silicon-cobalt
      hydrous oxide prepared from water glass and cobalt chloride. The formation of
      silicate fragments having smectite-type structure was studied by EXAFS.

PMID- 11512917
TI  - XANES study of charge ordering on the spin-Peierls phase transition of alpha'
      NAV2O5.
AB  - alpha'-NaV2O5 transforms at Tc = 34K, and the origin of the phase transition
      seems to be caused by the charge order and spin-Peierls mechanism. However the
      experiments which reveal the existence of charge order are very little. We
      measured XANES of V atoms which relates to the valence of V. It was found that
      the valences of V atoms in NaV2O5 were V4.5+ in the high temperature phase by
      comparing pre-edge and XANES of NaV2O5 with that of LiV2O5 CaV2O5 and V2O5. The
      analysis of EXAFS also shows the environment of the V4.5+ state.

PMID- 11512918
TI  - EXAFS study of Sb-Te alloy films.
AB  - The local structures of three phases; stable compound Sb2Te3, metastable
      crystalline c-SbTe and amorphous a-SbTe films having the atomic ratio Sb/Te=3: in
      Sb-Te system have been studied by EXAFS. The c-SbTe has a partly similar local
      structure to crystalline Sb2Te3. The a-SbTe film has a local structure of NaCl
      type, which is topologically analogous to the crystalline form. The amorphous
      phase has shorter bond distances 2.86A (around Sb-site) and 2.83A (around Te
      site) than the corresponding distances 2.89A and 2.87A in the crystalline phase.
      This unbalanced bond distances between the Sb-site and Te-site implies that site
      disordering occurs. Shortening of bond distances in the amorphous phase is due to
      the relaxation of locally distorted crystalline structure.

PMID- 11512919
TI  - Sb K-edge absorption fine structure of Sb2Te3.
AB  - In order to study the local structure of some antimony compounds, Sb K-edge XAFS
      spectra were measured for Sb2Te3 and InSb. The measurements were performed in the
      transmission mode at BL-01 of SPring-8. Though crystal structure of antimony
      telluride Sb2Te3 is known by X-ray diffraction analysis, the EXAFS analyses give
      controversial result on the Sb-Te distance and the coordination number of Sb2Te3.
      Comparing the observed XANES spectra for Sb2Te3 with FEFF8 calculation, we can
      explain the controversial results which are also supported by the observed X-ray
      powder diffraction.

PMID- 11512920
TI  - XANES analyses of silicon crystalline irradiated by nitrogen/oxygen ions.
AB  - X-ray absorption techniques have been applied to the characterization of 5 keV
      nitrogen / oxygen ions implanted silicon samples. The depth selective measurement
      of XANES by recording in PEY mode and the quantitative analysis by superposition
      of XANES spectra were carried out to elucidate the depth profile of implanted
      ions. It has been revealed that the silicon nitride phase were formed in silicon
      after prolonged N+ irradiation and it extended over the deep part of the damaged
      region from the surface. On the other hand, for the O+ irradiation, silicon
      dioxide phase were produced only in the shallow part of the damaged region, i.e.,
      the silicon dioxide phase likely broke off during the irradiation.

PMID- 11512922
TI  - XAFS theory studied by closed-path Green's function.
AB  - The basic framework of X-ray absorption fine structure (XAFS) theory is
      formulated by use of the non-equilibrium Keldysh-Green function, which presents a
      unified view of XAFS spectra at zero and nonzero temperature. In particular, the
      relation between the scattering Green's function and the retarded Green's
      function G' is discussed, along with resonance effects in XAFS. The latter
      effects give rise to unexpected peaks within one-electron theory. Loss effects,
      both intrinsic and extrinsic, are also discussed.

PMID- 11512921
TI  - Structure of new porous compounds after annealing in vacuum.
AB  - Dehydration process in recently synthesized porous inorganic salts formed by
      large cluster anions [Re6X8(CN)6]4- (X= S, Se), transition metal cations and
      water molecules has been investigated. Desolvation process of the complex
      Co(DMF)6[Mo6Br8(NCS)6], where DMF dimethylformamide. has been studied. CoK, MoK
      and ReL3 XAFS measurements of these new complicated compounds before and after
      annealing in vacuum at temperature up to 250 degrees C were performed. Changes of
      electronic and spatial structure of these compounds under the heating process
      have been established and adequate structural models of the amorphous compounds
      obtained are suggested and discussed.

PMID- 11512923
TI  - Local structure of liquid and solid silver halides probed by XAFS.
AB  - Investigation of the local structure of the high-temperature liquid and solid
      phases in the 300-725 K range of AgBr has been performed using the x-ray
      absorption spectroscopy (XAS). Structural results are compared with existing
      diffraction studies and computer simulations demonstrating the reliability of the
      XAS technique in determining the short-range structure. Present results on solid
      AgBr are in agreement with known thermal expansion data. The short-range g(r) of
      liquid AgBr is reconstructed showing the unique insight provided by the XAS
      technique in measuring short-range atom-atom correlations in liquids.

PMID- 11512924
TI  - Liquid Rb micrometric droplets confined in paraffin wax: an X-ray absorption
      spectroscopy study.
AB  - We have performed high-quality X-ray absorption measurements on crystalline (c
      Rb) and liquid (l-Rb) Rubidium in the range from 15 K to 320 K. Performing a
      consistent analysis that takes into account the contribution of the medium range
      structure, we observe that the l-Rb spectrum is compatible with pair correlation
      function g(r) previously determined by neutron diffraction experiments. Due to
      the micrometric size of the liquid droplets we were able to observe a slight
      undercooling down to 290 K. We were also able to study the details of the very
      strong multielectron excitations channels in terms of resonances, edges and shake
      off features at proper theoretical energy values.

PMID- 11512925
TI  - EXAFS measurements for liquid Ge-Si alloys.
AB  - EXAFS measurements around the Ge-K edge have been carried out for liquid Ge-Si
      alloys for the first time to investigate the local structure around a Ge atom. To
      perform the EXAFS measurements for the liquid alloys with high melting
      temperatures, a new sapphire cell have been developed. The measurements were
      carried out for the liquid alloys from 10% to 60% of Si and the crystalline ones
      from 10% to 70% of Si as a reference. EXAFS oscillations, x(k), are observed even
      at 1480 degrees C for liquid Ge(0.4)Si(0.6). The position of the first peak in
      the radial distribution function obtained from Fourier transform of x(k) is
      shifted towards smaller distance for liquid and crystalline alloys with
      increasing Si concentration. The results of a curve-fit analysis in a harmonic
      approximation show that Ge-Ge and Ge-Si bonds in the liquid alloys become long
      with increasing Si concentration while those become slightly short in the
      crystaline ones.

PMID- 11512926
TI  - Local structures of mechanically alloyed Fe100-xCux solid solutions studied by X
      ray absorption fine structure.
AB  - The local structures of the immiscible Fe(100-x)Cu(x) alloys (x= 0, 10, 20, 40,
      60, 80 and 100) produced by mechanical alloying have been investigated by XAFS.
      For the Fe(100-x)Cu(x) (x > or = 40) solid solutions, the local structures around
      Fe atoms change from bcc structure to fcc one and the Cu atoms maintain the
      original coordination geometry after milling for 160 hours. On the contrary, the
      local structures around Cu atoms in both of Fe80Cu20 and Fe90Cu10 alloys appear a
      transition from fcc to bcc structure. We found that the Debye-waller factor sigma
      of fcc Fe-Cu phase is larger than that of bcc Fe-Cu phase, and the sigma (0.099
      A) around Fe atoms is larger than that (0.089 A) of Cu in the Fe(100-x)Cu(x) (x >
      or = 40) solid solutions. This suggests that the mechanically alloyed Fe(100
      x)Cu(x) supersaturated solid solution is not a homogeneous alloy, and consists of
      Fe-rich and Cu-rich regions for various compositions. A possible mechanism for
      bcc-to-fcc and fcc-to-bcc changes in Fe(100-x)Cu(x) solid solutions is discussed
      in relation to the interdiffusion and transition induced by the ball milling.

PMID- 11512927
TI  - Structure and low-temperature thermal relaxation of ion-implanted germanium.
AB  - The structure of implantation-induced damage in Ge has been investigated using
      high resolution extended X-ray absorption fine structure spectroscopy (EXAFS).
      EXAFS data analysis was performed with the Cumulant Method. For the crystalline
      to-amorphous transformation, a progressive increase in bond-length was observed
      without the presence of an asymmetry in interatomic distance distribution (RDF).
      Beyond the amorphization threshold the RDF was dose dependent and asymmetric,
      where the bond-length and asymmetry increased as functions of ion dose. Such an
      effect was attributed to the formation of three- and five-fold coordinated atoms
      within the amorphous phase. Low-temperature thermal annealing resulted in
      structural relaxation of the amorphous phase as evidenced by a reduction in the
      centroid, asymmetry and width of the RDF, as consistent with a reduction in the
      fraction of non four-fold coordinated atoms. The results have been compared to
      other EXAFS studies of amorphous Ge, and it is suggested that the range of bond
      lengths reported therein is related to the sample preparation method and state of
      relaxation.

PMID- 11512928
TI  - EXAFS study on liquid gallium under high pressure and high temperature.
AB  - EXAFS (Extended X-ray Absorption Fine Structure) spectra of liquid gallium near
      the Ga K-edge have been collected in wide pressure and temperature ranges.
      Reliable short-range pair distribution functions have been determined using
      advanced ab-initio calculations (GNXAS) taking into account the medium and long
      range structure obtained by previous neutron and x-ray-scattering studies.

PMID- 11512929
TI  - Phase transitions in rare earth chlorides observed by XAFS.
AB  - XAFS spectroscopy has increasingly been utilised to elucidate the nearest
      neighbour structure in the condensed phases. In this paper, the XAFS spectra of
      NdCl3 and DyCl3 in both the solid and the liquid phases measured at the Nd and Dy
      L(III) absorption edges on beam line BM29 of the European Synchrotron Radiation
      Facility (ESRF) are presented. The Fourier transformed radial structure
      functions, phi(r) show that the prominent peaks corresponding to M-Cl (M: Nd or
      Dy) first shell contribution are shifted to shorter distances in the liquid melts
      as compared to those found in the corresponding solids. Similar behaviour has
      also been observed from other diffraction techniques in typical ionic melts such
      as NaCl. From the temperature dependence of the radial structure functions it is
      clear that the change in the M-Cl distance on melting is much larger in NdCl3
      than that in DyCl3.

PMID- 11512930
TI  - In situ XAFS study at the Zr K-edge for SiO2/ZrO2 nano-sol.
AB  - The structural characterisation of SiO2/ZrO2 nano-sol particles, prepared by
      mixing SiO2 sol and aqueous solution of ZrOCl2 8H2O, has been carried out by in
      situ XAS measurement at the Zr K-edge during condensation reaction. The detailed
      XANES features at the Zr K-edge of the mixed sol of SiO2/ZrO2 are compared with
      those of other references such as ZrO2, ZrOCl2 8H2O. BaZrO3, and ZrSiO4, and it
      becomes obvious that the Zr4+ ions are stabilised in an octahedral symmetry. The
      EXAFS result also indicates that each Zr atom is coordinated with six oxygen ones
      as the first nearest neighbour, where two oxygen atoms are from the linkage of
      (Si-O-Zr) at short distance, and four ones are from water molecules at long
      distance. As the condensation reaction proceeds, it is found that the number of
      oxygen atoms due to the formation of (Si-O-Zr) bond at short distance and the
      second neighbour of silicon atoms increase simultaneously. From the above EXAFS
      and XANES results, the structural and gelating models could be proposed, which is
      based on the octahedrally coordinated but distorted zirconium species attaching
      on the SiO2 sol surface.

PMID- 11512931
TI  - Crystallization process of transparent conductive oxides Zn(k)In2O(k+3).
AB  - Crystallization process of the homologous compounds Zn(k)In2O(k+3) from the
      coprecipitants was examined by XAFS spectroscopy and X ray diffractometry.
      Interesting crystallization behavior could be observed. Though zinc oxide already
      crystallized as the wurtzite-type ZnO at 573K, indium oxide remained amorphous.
      Subsequently bixbyite-type In2O3 appeared at 873K for k=5 and 7 and at below 773K
      for the other k-members, respectively. The InO distance in the amorphous In2O3
      was a little shorted than that in the bixbyite-type In2O3 by 0.06-7A. The
      distance remained constant but abruptly increased to that observed in the
      bixbyite-type In2O3 in accordance with the progress of crystallization. Then the
      distance gradually decreased and converged to ca. 2.12A at the temperature range
      of 1173-1373K, due to the reaction between In2O3 and ZnO to form the homologous
      compound.

PMID- 11512932
TI  - Structural modification on silica glass surface induced by thermal poling for
      second harmonic generation.
AB  - O-K edge XANES spectroscopy evidences structural modification induced by thermal
      poling treatment in surfaces of bulk Herasil silica glass presenting second
      harmonic generation. Considering model silicon dioxide clusters, calculations
      based on full multiple scattering approach have been performed in order to
      explain accurately the differences observed on XANES spectra at different stage
      of the poling treatment. These structural modifications on extreme surface affect
      both network and defects by breaking Si-O-Si bridging bonds. Despite of the
      formation of bridging bond occurring during the thermal depoling -which erases
      the SHG inside the glass-, the initial structure of the unpoled sample is not
      reproduced.

PMID- 11512933
TI  - Structural changes of quartz-type crystalline and vitreous GeO2 under pressure.
AB  - Using a large volume high pressure apparatus, quartz-type crystalline GeO2 and
      Li2O-4GeO2 glass have been compressed up to 14 GPa at room temperature and their
      local structural changes have been investigated by an in-situ XAFS method. In
      quartz-type crystalline GeO2, the change of the coordination number from 4 to 6
      begins above 8 GPa and finishes below 12 GPa. On decompression, reversal
      transition begins below 8 GPa and there is a large hysteresis. Almost no sixfold
      coordination of Ge is preserved after releasing pressure. Change of coordination
      number in vitreous Li2O-4GeO2 begins above 6 GPa and is completed below 10 GPa.
      Reversal transition begins below 10 GPa and the hysteresis is smaller than that
      of quartz-type GeO2. Change of coordination number in vitreous Li2O-4GeO2 is also
      reversal.

PMID- 11512934
TI  - Structural approach of CsCl-modified Ga2S3-La2S3 glasses.
AB  - Gallium-lanthanum sulfide glasses have specific interesting physical properties,
      as semiconductor behavior and good transmission at long wavelengths. The addition
      of CsCl increases the thermal stability region of the glass making it suitable
      for many applications in optoelectronics. Ga2S3-La2S3 glasses modified by 10 to
      40% CsCl have been studied by X-ray absorption spectroscopy, at the chlorine K
      edge and at the gallium K edge at 9 K, in order to get information about the
      actual structural role of CsCl. The chlorine environment is similar to that in
      CsCl. The gallium coordination sulfur polyhedra are weakly distorted tetrahedra.
      identical for all samples. The low temperature measurements shown that the
      polyhedral corner linkage is also unaltered by the addition of CsCl.

PMID- 11512935
TI  - X-ray induced reduction of rare earth ion doped in Na2O-Al2O3-B2O3 glasses.
AB  - 5Na2O-10Al2O3-85B2O3 glasses doped with 0.05 mol% Sm2O3 or 0.05 mol% Eu2O3 turn
      to orange after irradiation by focussed femtosecond pulsed laser or x-ray
      irradiation. To know the mechanism of photo-induced coloring, the glasses were
      studied by Sm or Eu L(III) XANES before and after x-ray or UV irradiation. XANES
      in both edges showed that a part of trivalent ion converted to divalent ion upon
      the irradiation of x-ray. These facts reveal that photoreduction of rare earth
      ion is the mechanism of photo-induced coloring. However no photoreduction upon UV
      irradiation occurred in both glasses.

PMID- 11512936
TI  - EXAFS study of PbS-SnS solid solution.
AB  - The local environment of the Pb atom in Pb(x)Sn(1-x)S solid solution was studied
      by EXAFS technique. The shortest Pb-S bond length in orthorhombic samples was
      found to be by approximately 0.2 A shorter than in cubic PbS. This indicates that
      the 6s2 lone pair of Pb is stereochemically active in the SnS host. Strong
      correlations found in the distribution of metal atoms in the second shell show
      that the orthorhombic samples can be considered as solid solutions with
      unexpectedly strong short-range order. One can expect that the short-range order
      in PbSnS2 may result in formation of superstructures with space groups C(7)2v or
      C(2)2v.

PMID- 11512937
TI  - EXAFS study of phase transitions in KIO3.
AB  - The iodine K-edge EXAFS study of KIO3 was performed to clarify local structural
      changes on the successive phase transitions. The pair-distribution function of
      three oxygen atoms in an oxygen octahedron is almost independent on temperature
      like a covalent bond, whereas that of the other three is gradually reduced with
      increasing temperature like an ionic bond. The result indicates that iodine and
      oxygen atoms exist as an IO3- molecule in a pseudo-perovskite-type structure. The
      anomalous behavior in the Debye-Waller factor for the latter pair-distribution
      function appears around 50 K, which is associated with the orientational glass
      transition.

PMID- 11512938
TI  - EXAFS study of glass transition in K1-x(NH4)xI.
AB  - The iodine K-edge EXAFS study of K1-x(NH4)xI mixed crystals was performed to
      clarify the local structure of the dipole glass associated with the random
      reorientational freezing of ammnonium ions. The pair-distribution function of the
      nearest iodine-iodine ions is strongly reduced with increasing ammonium
      concentration. The reduction originates in the local distortion of lattice
      induced by the short-range antiferroelectric order of ammonium ions. We discuss
      the relationship between the reorientational freezing of ammonium ions and the
      local distortion of lattice in comparison with the results of X-ray diffraction
      measurements.

PMID- 11512939
TI  - Local atomic and electronic structure of Al90FexCe10-x alloys: XAFS analysis.
AB  - X-ray absorption fine structure (XAFS) above the Fe K-edge and the Ce L3-edge in
      amorphous Al90Fe(x)Ce10-x (x = 3, 5, and 7) alloys have been measured and
      analyzed. Quantitative analyses of the Fe K-edge and Ce L3-edge EXAFS spectra are
      limited to local structure parameters of the first coordination sphere. Using a
      theoretical multiple scattering (MS) approach, we show that the Fe and Ce XANES
      are sensitive to the structure of coordination spheres, which extend up to nearly
      4.5 A. Comparison of experimental XANES spectra with theoretical MS results
      allows one to determine the local structure around the iron and cerium sites up
      to at least the third shell of atoms.

PMID- 11512940
TI  - Investigation of undercooled liquid metals using XAFS, temperature scans and
      diffraction.
AB  - Novel techniques and the experimental station for experiments on condensed matter
      under extreme conditions that have been developed at the BM29 beamline of the
      European Synchrotron Radiation Facility (ESRF) are described. The experimental
      setup includes facilities to collect high-quality extended X-ray absorption fine
      structure (EXAFS) spectra, to perform controlled temperature scans while
      monitoring the sample absorption for the direct detection of phase transitions,
      and to collect high-resolution energy-scanning X-ray diffraction (ESXD) data,
      with recent enhancements through the installation of a two-channel collimator
      detector system. Facilities for X-ray absorption temperature scans, introduced
      five years ago, are now exploited for a wide variety of purposes. A method for
      the measurement of the nucleation rate in undercooled liquids has been proposed
      recently. All these advances in the experimental setup and techniques, combined
      with a simple but rigorous X-ray absorption fine structure (XAFS) data analysis
      scheme for disordered matter, have contributed to make feasible challenging
      experiments on undercooled liquid matter that were not even conceivable only a
      few years ago. An example of the application of these methods to undercooled
      liquid indium (In) is presented.

PMID- 11512941
TI  - XANES spectra of mechanical alloyed Y-Cu system.
AB  - We report changes in the structure and the electronic states of YCu2 during
      mechanical alloying. The x-ray diffraction shows that milling for about 60 h
      transforms mixture of elemental powders of Y and Cu into an amorphous alloy. We
      have measured the x-ray absorption near edge structure (XANES) spectra of
      mechanically alloyed YCu2 at Cu K and Y K edges at various milling time. The pre
      edge peak near the Cu K threshold grows remarkably and its central energy
      decreases with increasing the milling time. The absorption near the Y K
      threshold, on the other hand, decreases with milling time. We discuss these
      features of XANES spectra in connection with the phase transformation from the
      crystalline to amorphous states.

PMID- 11512942
TI  - XANES study in the solid state reaction of Zr-Ni system.
AB  - We have measured x-ray absorption near edge structure (XANES) spectra of
      mechanically alloyed ZrNi near Ni and Zr K edges as a function of milling time.
      The x-ray diffraction shows that the system is transformed into an amorphous
      phase by milling for about 60 h. With increasing the milling time, a small
      absorption near the Ni threshold rises and finally forms a peak in the amorphous
      phase, while an absorption near the Zr threshold shows a gradual decrease. The
      peak of the Ni K edge reflects 3d character strongly hybridized with 4p states,
      while the absorption of the Zr K edge comes from states having a 4d orbital
      character.

PMID- 11512943
TI  - O K and Cu LIII edge study of itinerant holes in I2-, Hgl2- and HgBr2-
      intercalated BSCCO(2212) single crystals.
AB  - Intercalation effect on BSCCO (2212) system, although it increases the interlayer
      distance and the c-axis remarkably, produces only a small change in the
      transition temperature. Thus, amongst other things, intercalation provides an
      effective method to investigate the influence of the interblock coupling.
      Electrons are transferred from the host Cu-O2 layers to the guest molecules I2,
      HgBr2, HgI2 leading to evolution of the Tc. For this we have made high resolution
      XANES study on the O K and Cu L3 edges to estimate the density of the doping
      holes. We attempt on basis of our and earlier results the evolution of Tc in
      these as also the much larger decrease produced in Tc for I2-intercalation for
      which the increase in basal spacing is the smallest of the three halides.

PMID- 11512944
TI  - Simultaneous measurement of XANES in halide-intercalated BSCCO(2212) using
      electron and fluorescence yield to compare their performance.
AB  - Total Yield with an escape depth of approximately 100-200 A is known to be rather
      surface sensitive. Fluorescence Yield, on the other hand, with an escape depth of
      approximately 1000-2000 A is relatively less prone to surface effects but
      necessitates some corrections to obtain the true signal. Both have their plus and
      minus points and, if used with care, yield reliable data. In the present
      experiment both the techniques have been simultaneously employed for measuring
      orientation dependent O K and the Cu L3 edges from an uncleaved surface of
      I(2)BSCCO(2212) single crystal to compare the performance of the two modes of
      detection. Despite glaring differences in intensities the results from the two
      appear to show reasonable agreement in respect of relative intensities of the
      spectral features.

PMID- 11512945
TI  - XAFS and X-ray reflectivity study of III-V compound native oxide/GaAs interfaces.
AB  - Fluorescence-mode XAFS has been used to study the local environment about chosen
      atomic species such as Ga and As in bulk oxide Al(1-x)Ga(x)As (x=0.96) and at the
      interface between thin (300 A) oxidized Al(1-x)Ga(x)As (x=0.94) film and GaAs
      substrate in total external-reflection mode. X-ray reflectivity experiments have
      also been employed to investigate the density profile of the oxide film on a GaAs
      substrate revealing the density profile as a function of depth. It is important
      to find out how the As is incorporated at the interface, the interfacial strain,
      and related local structural parameters for understanding that may be central in
      developing high performance III-V MOSFET devices.

PMID- 11512946
TI  - X-ray absorption spectroscopy investigations on oxidized Ni/Au contacts to p-GaN.
AB  - X-ray absorption spectroscopy was used to investigate the electronic structure of
      as-deposited and oxidized Ni/Au contacts to p-GaN and to elucidate the mechanism
      responsible for low impedance. X-ray absorption near edge spectra of Ni K- and
      L3,2-edges clearly indicate formation of NiO on the sample surface after
      annealing. The reason for low impedance may be attributed to increase in hole
      concentration and existence of p-NiO layer on the surface.

PMID- 11512947
TI  - Local structures of nanocrystalline GaN studied by XAFS.
AB  - X-ray absorption fine structure (XAFS) was used to investigate the local
      structures around Ga atoms in the hexagonal nanocrystalline and crystalline GaN
      under 78 and 300 K. For the first nearest neighbor coordination shell of Ga-N.
      the average bond length R (0.194 nm), coordination number N (4.0), thermal
      disorder sigma (0.0052 nm) and static disorder sigmaS (0.0007 nm) are neatly
      independent of the measured temperature and crystalline state. This indicates
      that the Ga-N covalent bond is much stronger, and the 4 nitrogen atoms in first
      nearest neighbor around Ga atoms keep the tetrahedral structure (Td). For the
      second nearest neighbor coordination shell of Ga-Ga, their bond lengths are about
      0.318 nm. However, the sigmaS (0.0057 nm) of nanocrystalline GaN is 0.0047 nm
      larger than that of crystalline GaN (0.001 nm), and the sigmaT of nanocrystalline
      is 0.0053 nm and 0.0085 nm at the temperature of 78 and 300 K, respectively. The
      result indicates that the difference of local structure around Ga atoms between
      nanocrystalline and crystalline GaN occurs mainly at the Ga-Ga second nearest
      neighbor coordination shell. The reason is explained as the local lattice
      distortion and unsaturated surface atoms existing in nanocrystalline GaN.

PMID- 11512948
TI  - Polarized XAFS study of high-temperature phases of NaNbO3.
AB  - Temperature dependence of the Nb displacement relative to the center of oxygen
      octahedron in NaNbO3 has been studied by polarized Nb K XAFS. Spectra were
      measured at two orientations of a single crystalline sample. Room temperature
      EXAFS data are in a good agreement with earlier X-ray diffraction data: Nb
      antiferroelectric displacements were found to be orthogonal to the b axis.
      Analysis of the temperature dependent EXAFS data didn't reveal any abrupt changes
      of Nb-O distances in the phase transition points. In all high-temperature
      paraelectric phases Nb appeared to be displaced to the off-center positions.
      Displacements, orthogonal to b axis, remained almost constant, while displacement
      along b axis gradually increased with temperature, so that in the cubic phase the
      displacements along all axes became equal. This shows, that disorder plays an
      important role in the high temperature phases. The above results are supported
      also by the analysis of the pre-edge structure, - the integral intensity of the
      pre-edge peak was temperature-independent when the polarization vector of the X
      rays was orthogonal to b axis and gradually increased with temperature when the
      polarization was parallel to b.

PMID- 11512949
TI  - Charge order and superconductivity in low-dimensional organic conductors.
AB  - We study the coexistent state of the spin density wave (SDW) and the charge
      density wave (CDW) in a one-dimensional extended Hubbard model. We find that the
      coexistent state of SDW and CDW is stabilized in various electron-filling cases
      when band parameters are for organic conductors. The ground state energies have
      cusp-like minima at n/4m-fillings, where n and m are integers. The maxima of the
      critical temperatures of the coexistent state at n/4m-fillings will be observed
      in X-ray scattering measurements. We discuss the suitable filling for
      superconductivity of which strong fluctuation in antiferromagnetic ordering may
      be the origin.

PMID- 11512950
TI  - X-ray absorption spectroscopy studies of Ba(1-x)Ca(x)TiO3.
AB  - We report x-ray absorption near edge spectroscopy (XANES) of Ca and O K-edges of
      Ba(1-x)Ca(x)TiO3 (x = 0, 0.01, 0.08, 1) and understand the spectral features
      related to the electronic structure of these perovskites. The XANES spectra of Ca
      K-edge possess a pre-edge peak similar to other 3d transition metals like Ti, Ni
      when present in perovskite structure and provides information about p-type or
      hole doping. Presence of considerable amount of 3d states justifies the reason to
      consider it as a light 3d transition metal. The O K-edge spectra display
      characteristic spectral features assigned as e(g) and t2g and show strong
      dependence on concentration.

PMID- 11512951
TI  - Polarization-dependent XANES study of Bi2Sr2Ca(1-x)Pr(x)Cu2O8-delta insulating
      single crystal.
AB  - Pr doping has been extensively studied in cuprate superconductors to understand
      the mechanism of quenching of superconductivity in cuprate perovskites.
      Experience has revealed that it acts differently in different cuprate
      perovskites. We have made high resolution polarization XANES measurements on a Pr
      doped single crystal within the ab-plane on the Cu K and Pr L III absorption
      edges to ascertain the valence state of Pr cation and thereby try learning how it
      is quenching superconductivity in the present case. Our results show that besides
      the Pr quenching holes the possibility of its localizing some holes through
      hybridization with O 2p and Cu 3d cannot be ruled out.

PMID- 11512952
TI  - Lattice softening in superconducting compositions of Ba(K)BiO3.
AB  - Temperature dependent x-ray absorption spectra investigation were measured for
      Ba(1-x)K(x)BiO3 (Bi L3-edge) with x =0.0, 0.25, 0.4, 0.5 and for BaPbO3 (Pb L3
      edge). It was found that at low temperatures the Debye-Waller factor of the
      square diagonal Bi-Bi bond has the maximum value near the insulator-metal phase
      transition for the compound with x = 0.25 and x = 0.4. Temperature dependence of
      the Debye-Waller factor of Bi-Bi bond strongly differs from the Einstein model
      curve that well describes the harmonic systems (for example BaPbO3). This
      behavior is consistent with the strong anharmonicity of the Bi-O shell due to the
      double-well vibration potential reported by us earlier. Presented results point
      to the essential lattice softening of the superconducting compositions, which is
      important for the understanding of superconductivity mechanism in perovskite type
      oxides.

PMID- 11512953
TI  - Local lattice distortion in high-Tc cuprates.
AB  - The dynamical local lattice distortion in the CuO2 plane of the cuprate high
      temperature superconductors is investigated with the numerical diagonalization
      study for finite clusters of t-J model. It is found that the in-plane vibrations
      of the oxygens play an important role in the formation of some static orders like
      CDW and SDW through the polaronic self localization effect. The 1/8 problem is
      also discussed based on the present result.

PMID- 11512954
TI  - Multiple scattering approach to K-edge XANES of Sb-Te systems.
AB  - The Sb-Te systems are important for optical memories. The local structures of
      these Sb-Te systems are crucial to understand the properties. Here we study three
      different Sb-Te systems, Sb2Te3, c- and a-SbTe (c; crystalline, a; amorphous) by
      use of XANES analyses. The present calculations for Sb2Te3 system show quite good
      agreement with the observed spectra. In contrast to Sb2Te3 system, both c- and a
      SbTe systems, in which a ratio of Sb to Te is 3, are metastable; both of the
      structures have not been known yet. We thus investigate these local structures by
      use of the multiple scattering approach, and propose a possible model for each of
      c- and a-SbTe.

PMID- 11512955
TI  - Bond length determination in Cu-Mg-O by EXAFS spectroscopy.
AB  - Magnetic semiconductors such as Cu(x)Mg(1-x)O, which are perspective materials
      for high-temperature superconductivity have been studied by EXAFS. The new
      technique of obtaining information from EXAFS-data has been described. It is
      based on the special iterative algorithm of solving an inverse ill-posed problem
      on the determination the partial pair correlation functions (pPCFs). Bond lengths
      of the nearest neighbours have been determined. It was clearly shown that the
      short range order in compound Cu0.2Mg0.8O differs from a hypothetical alloy with
      MgO structure and from the copper oxide.

PMID- 11512956
TI  - EXAFS study of crystal structures of (Ba1-xLax)2In2O5+x and their oxide ion
      conductivity.
AB  - Crystal structures of(Ba1-xLax)2In2O5+x (x=0.00, 0.20, 0.30, 0.40, 0.50) were
      analyzed by EXAFS and the powder X-ray Rietveld method. A Fourier transform of In
      K-edge EXAFS data from (Ba1-xLax)2In2O5+x showed a peak between 1.2 and 2.0 A
      attributed to the nearest oxide ions around In3+ cation. The peak as back-Fourier
      transformed, and the structural parameters were refined by the least square
      fitting. The coordination number of In3+ cation increases with increasing La3+
      cation) content. This means oxygen is introduced at interstitial site by keeping
      an electroneutrality. As a result of the oxygen distribution, the oxide ion
      vacancies distribute randomly. The electrical conductivities of (Ba1-xLax)2In2O5
      rapidly increased above 1203 K due to the order-disorder transition of oxygen
      vacancy. On the other hand, the electrical conductivities of (Ba1-xLax)2In2O5+x
      (x=0.20, 0.30, 0.35. 0.40, 0.45, 0.50) did not show the sharp discontinuity in
      the conductivity because the disorder phase of defective perovskite type
      structure was stabilized by doping La3+ cations at A-site even at low
      temperature.

PMID- 11512957
TI  - A study of titanium nitride diffusion barriers between aluminum and silicon by X
      ray absorption spectroscopy: the Si, Ti and N results.
AB  - We report a multi-elment, multi-edge and multi-detection mode X-ray
      photoabsorption study of a series of Al/TiN(x)/Si(100) thin films as a function
      of the TiN(x) film thickness (100A-500A) and of the annealing temperature (400
      degrees C-600 degrees C). The Si K- and L-edge results show that Si does not
      diffuse to the surface for all the films. The high resolution Ti L-edge and N K
      edge spectra show that the TiN(x) layer undergoes a dramatic chemical reaction
      with the gradual increase in the annealing temperature. This chemical reaction
      stabilizes at 560 degrees C at which the TiN(x) film is known to fail to act as
      an effective diffusion barrier between Al and Si.

PMID- 11512958
TI  - XAFS study of LiCo1-xFexO2 cathode for rechargeable lithium battery by laboratory
      XAFS spectrometer.
AB  - The change of local structure in layered-rock-salt-type iron doped lithium
      cobaltate LiCo(1-x)Fe(x)O2 under electrochemical Li de-intercalation (charge) /re
      intercalation (discharge) was studied by a laboratory type XAFS spectrometer. In
      Co K-XANES and Fe K-XANES of LiCo0.85Fe0.15O2 the absorption peak shifted to
      higher energy by 1.5-2eV for Co K-edge and by 2-2.5eV for Fe K-edge,
      respectively, after the first charge. The spectra returned close to initial
      position and had almost original shape after the first discharge. In Co K- and Fe
      K-EXAFS of LiCo0.85Fe0.15O2 during the first charge and discharge the reversible
      change of the local structure was observed mainly around the Co atoms although
      the partly irreversible change of the local structure was found around the Fe
      atoms. The variation of local structure occurred in similar manner for the
      samples with x=0.05 and 0.25. This indicates that both Co3+/Co4+ and Fe3+/Fe4+
      redox reactions occur reversibly during the first charge and discharge.

PMID- 11512959
TI  - In situ XAS study of LixNi0.7Fe0.15Co0.15O2 cathode material.
AB  - We have examined the oxidation states and local atomic structures of Ni, Fe, and
      Co in Li(x)Ni0.7Fe0.15Co0.15O2 as a function of Li content during the first
      charge in a Li/Li(x)Ni0.7Fe0.15Co0.15O2 nonaqueous cell. We show that the
      composition of the material in the pristine state is more accurately described by
      Li0.95Ni(II)0.09Ni(III)0.66Fe(III)0.15Co(III)0.25O2 Half of the Ni(II) resides in
      Li-vacant sites. Both Fe and Co substitute for Ni within the NiO2 slabs with no
      significant amounts of Fe or Co that can be attributed to Li-vacant sites. The
      local structure parameters are consistent with oxidation states observed on the
      basis of the XANES data. The Ni K-edge energy continuously shifts to a higher
      energy with decrease in Li content due to oxidation of Ni(II) to Ni(II) and
      Ni(III) to Ni(IV). After the complete oxidation of Ni(III) to Ni(IV), the Fe K
      edge energy begins to increase with further decrease in Li content indicating the
      oxidation of Fe(III) to Fe(IV). The Co K-edge energy at half-height, on the other
      hand, is unchanged during the whole range of Li deintercalation indicating that
      no significant change in the oxidation state of Co occurs upon the complete
      removal of Li.

PMID- 11512960
TI  - In situ XAFS study on cathode materials for lithium-ion batteries.
AB  - Ni and Co K-edge X-ray absorption spectra of LiNi0.8Co0.2O2 have been collected
      using in situ coin cells. To investigate the electronic and structural changes
      accompanied by the capacity fading during electrochemical cycling and keeping
      batteries at high temperatures, the cells with different cycling states and
      keeping conditions (temperature, time) were prepared. Upon charging the cell, the
      Ni and Co K absorption edge shifted towards higher energy, and the good
      correlation between the range of chemical shifts upon charging and the capacity
      of the cell was observed. From quantitative analysis of EXAFS data, it was
      revealed that the capacity fading is closely related to the Jahn-Teller
      distortion of the NiO6 octahedron.

PMID- 11512961
TI  - Path-integral approach to anharmonic vibration of solids and solid interfaces.
AB  - The temperature dependence of EXAFS (extended X-ray absorption fine structure)
      cumulants was investigated for bulk Cu and a thin film of Cu by means of the path
      integral effective classical potential method. By using the semi-empirical
      embedded-atom method as a potential, agreement between the experiments and
      calculations is found to be excellent for bulk Cu. In the thin Cu(111) film,
      anisotropic anharmonic vibration was clearly observed; the out-of-plane vibration
      is much more enhanced and more anharmonic than the lateral vibration. The results
      are semiquantitatively consistent with the previous experimental data on
      Cu(111)/graphite. Such a vibrational enhancement should be the driving force for
      the roughening transition and/or the surface pre-melting at higher temperature.
      The practical usefulness of the path-integral effective classical potential
      method combined with the embedded-atom method is demonstrated.

PMID- 11512962
TI  - Changes in electronic structure by Li ion deintercalation in LiCoO2 from cobalt L
      edge and oxygen K-edge XANES.
AB  - Cobalt L-edge and oxygen K-edge X-ray Absorption Near Edge Structure (XANES)
      investigated change in electronic structure by electrochemical lithium ion de
      intercalation in LiCoO2. The Co L-edge XANES of Li(1-x)CoO2 did not show any
      chemical shift even at high x value. The oxygen K-edge XANES of Li(1-x)CoO2
      indicated that the holes compensating the lithium ion deintercalation are located
      primarily in the oxygen 2p states rather than in the Co 3d states.

PMID- 11512963
TI  - Studies of impurities in magnetic semiconductors: an example of important XAFS
      applications.
AB  - The x-ray absorption fine structure (XAFS) technique has been employed to
      investigate the local structure and valency about Mn and Fe ions in the III-V
      diluted magnetic semiconductors In(1-x)Mn(x)As and Ga(1-x)Fe(x)As, prepared by
      molecular-beam-epitaxy under various growth conditions. These new systems are
      promising magnetic materials of considerable current interest and with important
      technical applications including photo-carrier induced magnetism and spin
      polarized current devices. The local structure around the magnetic ions can play
      a pivotal role in affecting the magnetic properties of these semiconductors.
      Local structure information obtained from XAFS has provided the first direct
      evidence that the magnetic impurities can indeed substitute for the cation host
      atoms in samples prepared under appropriate conditions.

PMID- 11512964
TI  - Structural properties of Cu-Permalloy under annealing.
AB  - We have studied the structure of melt-spun copper-permalloy samples
      (Cu80Fe4Ni16), annealed at several temperatures up to 873 K by means of EXAFS
      spectroscopy. The results for iron first neighhor average distance showed a slow
      decrease for annealing temperatures higher than 673 K. The nickel first neighbor
      distance had almost no change in the whole temperature range. This behavior is
      discussed in the light of rich iron cluster formation, and is compared with
      magnetic measurement results.

PMID- 11512965
TI  - Growth induced magnetic and chemical anisotropy in CoPt3 alloy films.
AB  - We report the results of polarized Co EXAFS experiments on a series of CoPt3
      films grown by molecular beam epitaxy on (100) MgO singe crystal substrates over
      a range of temperatures from 473 K to 1073 K. These samples exhibit substantial
      perpendicular magnetic anisotropy that is strongly dependent on the substrate
      growth temperature Tg. We measure a preference for in-plane Co-Co pairs that is
      correlated with the magnetic properties.

PMID- 11512966
TI  - Observation of the segregation and the dissolution of the Co and the Cu in CoCu
      metastable alloys.
AB  - Metastable Co(x)Cu100-x(x=5, 10, 15, 20) alloys have been annealed at increasing
      temperatures in order to study the evolution of the Co cluster and its relation
      with the magnetotransport properties. The structure was investigated by X-ray
      Absorption Spectroscopy on the Co K-edge as a function of composition and
      annealing temperature.  An anomalous trend in the structural evolution has been
      evidenced and related to the preculiar features observed in the magnetotransport
      properties.

PMID- 11512967
TI  - A Fe(x)Mn1-x/Ir(001) multilayer probed by EXAFS and DAFS.
AB  - Diffraction Anomalous Fine Structure (DAFS) and EXAFS measurements have been
      performed on a (Fe0.7Mn0.3)/Ir(100)40 super-lattice at the K-edges of Fe and Mn.
      Theoretical EXAFS spectra have been refined: a slight difference in the first
      neighbor distance suggests a non homogeneous distribution of the Mn in the alloy.
      The smooth features of the DAFS spectra have been modeled to study the
      composition and the strain profile along the growth axis.

PMID- 11512968
TI  - Local structure evolution of FexNi77-xCu(1-)Nb2P14B6 soft magnetic materials by
      mechanical alloying.
AB  - Mechanically alloyed Fe(x)Ni77-xCu1Nb2P14B6 soft magnetic materials have been
      prepared with different atomic compositions. The alloy structures are
      investigated by X-ray absorption fine structure (XAFS). The results show that
      mechanical alloying (MA) can drive the Fe(x)Ni77-xCu1Nb2P14B6 powder mixture to
      produce amorphous alloy while the atomic concentration of Fe element is about and
      over 40%. On the contrary, the MA Fe(x)Ni77 xCu1Nb2P14B6 is a solid solution with
      a fcc-like structure in the region of lower Fe atomic concentration (<22%),
      preserving a medium-range order around Ni and Fe atoms. Moreover, we have found
      that the local structure geometry of Fe atom is similar to that of Ni atom for
      all the MA Fe(x)Ni77-xCu1NbP14B6 samples. It indicates that the local structures
      of Fe and Ni atoms in a Fe(x)Ni77-xCu1Nb2P14B6 sample only depend on the x value
      of element Ni after ball milling.

PMID- 11512969
TI  - Mn K-edge XANES spectra of manganites measured by Kbeta emission.
AB  - The electronic state of Mn atoms in mixed valence manganites has been studied by
      means of X-ray absorption spectroscopy at the Mn K-edge. Higher resolution than
      in conventional measurements has been achieved by measuring the Mn Kbeta
      fluorescence line. We have found a unique resonance at the edge in the XANES
      spectra of intermediate composition RE1-xCa(x)MnO3 samples. The features of these
      XANES spectra do not depend on small changes in the local structure around the Mn
      atom. However, the spectra of the intermediate composition samples can not be
      reproduced by a linear combination of REMnO3 and CaMnO3 spectra. Accordingly, the
      electronic state of Mn atoms in these compounds can not be considered as a
      mixture of Mn3+ and Mn4+ pure states.

PMID- 11512970
TI  - Has charge ordering actually been observed in manganites by resonant X-ray
      scattering?
AB  - The comparison between X-ray resonant scattering experiments and X-ray absorption
      data shows that no real Mn3+/Mn4+ charge ordering occurs in manganites with
      Mn3+/Mn4+=1 ratio. However, these experiments demonstrate the presence of two
      different types of manganese atoms with a different local geometrical structure.
      A structural model, which accounts for both X-ray absorption and resonant
      scattering experiments, is proposed.

PMID- 11512971
TI  - Theoretical study of Mn K-edge in La1-xCaxMnO3.
AB  - Effects of (i) local magnetic ordering, (ii) lattice distortions, and (iii) Mn 3d
      - O 2p hybridization on the shape of Mn K- edge XANES spectra of La1-xCa(x)MnO3
      have been evaluated numerically and compared with available experimental data. We
      calculated the spin-polarized Mn K-edge spectra. An energy splitting between spin
      up and spin-down XANES of 0.5-1.1 eV contributes to the broadening of the total
      XANES below T(N)(T(C)). To simulate lattice polaronic distortions across a MI
      transition the Mn K-edge spectra were calculated twice: assuming R-3c (R=1.96 A)
      and Pbnm (R1=1.91, R2=1.97, and R1=2.16 A) symmetries. Results could
      qualitatively reproduce the observed energy "shift" across the transition. A pre
      edge peak at E approximately 6542 eV and feature B3 at approximately 6 eV above
      the main peak were found to be related to the Mn 3d - O 2p hybridization. The
      feature B3 should be assigned to a shake-up transition. The calculated K-edge
      spectrum was obtained as a convolution product of the single-electron XANES and
      the spectrum of many-body excitations in the Mn-O electronic states in the
      presence of the 1s core-hole.

PMID- 11512972
TI  - Local structure and oxidation state of Mn and Ni atoms in LaNi1-xMnxO3+delta
      perovskites.
AB  - X-ray absorption spectroscopy has been used to study LaNi1-x Mn(x)O3+delta
      perovskites (x = 0.1, 0.25, 0.5, 0.75, 0.9). We have analysed both, the oxidation
      state and the local structure around the transition metal atoms. XANES spectra of
      these samples suggest a mixed valence state for both transition metal atoms. The
      Mn K-edge is shifted to high energies as the Ni content is increased up to x=0.5.
      The opposite behavior is found instead, for the Ni K-edge. Samples with x=0.5 and
      x=0.25 present the Mn K-edge at the same energy but the absorption features are
      different for both samples. The local structure has also been studied by means of
      the EXAFS technique. The first coordination shell nicely reflects the structural
      change observed in this series from rhombohedral perovskites (x>0.5) to
      orthorhombic perovskites x<0.5). The changes in the local structure for Ni and Mn
      atoms agree with the variation of the oxidation state observed in the XANES
      spectra.

PMID- 11512973
TI  - Geometric local structure at the Mn site in charge-ordered mixed valence
      manganites.
AB  - An extensive study of Mn K-edge absorption sepctroscopy has been carried out in
      La(1-x)Ca(x)MnO3 and Tb(1-x)Ca(x)MnO3 (x=0, 0.33, 0.5, 0.67, 1) series as a
      function of temperature.  The EXAFS analysis for the charge ordering compounds (x
      > or = 0.5) shows the presence of a static distortion of the MnO6 octahedron in
      the whole temperature range. However, this local distortion is lower than the
      distortion found for Jahn-Teller compounds. Magnetoresistive compounds (x=0.33)
      show a regular octahedron in the low temperature metallic phase. Instead, no
      changes are found for the first coordination shell (Mn-O) across the charge
      ordering transition while Mn-Mn distribution shows minor variations with the
      temperature. The structural analysis of the second coordination shell suggests
      that the Mn-O-Mn angle is the most relevant parameter to describe the electric
      and magnetic behaviour of these compounds.

PMID- 11512974
TI  - Soft x-ray absorption spectra of ilmenite family.
AB  - We have carried out soft x-ray absorption spectroscopy to study the electronic
      structure of ilmenite family, such as MnTiO3, FeTiO3, and CoTiO3 at the soft x
      ray beamline, BL23SU, at the SPring-8. The Ti and M L2,3 absorption spectra of
      MTiO3 (M=Mn, Fe, and Co) show spectra of Ti4+ and M2+ electron configurations,
      respectively. Except the Fe L2,3 spectrum, those spectra were understood within
      the O(h) symmetry around the transition metal ions. The Fe L3-edge spectrum
      clearly shows a doublet peak at the L3 edge, which is attributed to Fe2+ state,
      moreover the very high-resolution the L-edge spectra of transition metals show
      fine structures. The spectra of those ilmenites are compared.

PMID- 11512975
TI  - Structural properties of Y1-xYbxNi2B2C synthesized at high pressure: EXAFS data
      analysis.
AB  - Local structure of Y(1-x)Yb(x)Ni2B2C series synthesized at high pressure 8 GPa
      has been studied using EXAFS. Measurements were performed at the Ni K-edge in
      temperature range 5-300 K. The results show that the Debye-Waller factor for Ni
      Ni bond in the parent YNi2B2C compound is characterized by the Einstein
      temperature O(E) = 350 K, while a minimum value O(E) = 300 K is reached for the
      compound with = 0.025, which has the highest critical temperature T(c) = 12.5K of
      the superconductive transition. This correlates with the further suppressing of
      superconductivity and with the appearance of the local magnetic moments in the
      investigated Y(1-x)Yb(x)Ni2B2C series for x > or = 0.05 compounds. Observed
      changes in the local electronic and the local crystal structure of this system as
      a function of Yb concentration and of temperature were explained in the frame of
      the band filling effect.

PMID- 11512976
TI  - Characterization of relaxed photo-excited magnetized states in prussian-blue
      analogous magnets.
AB  - Local structure of a photo- or x-ray-induced ferrimagnet Cs0.8Co1.3 [W(CN)8](3
      cyanopyridine)1.9 x 2.1H2O was investigated by means of Co K- and W L-edge XAFS
      spectroscopy. The Co K-edge XANES spectra provide quantitative information on the
      ratio of Co(II) and Co(III) by virtue of the factor analysis. It was found that
      the Co(II) ratios are 81.9% at 300 K and 32.7% at 150 K. When the sample was
      irradiated by x rays at 30 K, a phase transformation occurred in a similar manner
      to the visible-light irradiation and a relaxed excited state that exhibits
      ferrimagnetism was formed. The relaxed excited state gives the Co(II) ratio of
      67.0%. The W L(III)-edge EXAFS spectra determine the W-C, W-N and W-Co distances.
      The results of the distances were obtained as R(W-C)=2.16 A, R(W-N)=3.31 A, R(W
      CoII)=5.37 A and R(W-CoIII)=5.19 A, irrespective of the three phases. The local
      structure of the relaxed excited state was found to be identical with that of the
      high-temperature (300 K) phase. The phase transformation is concluded to be
      caused by the charge transfer and the spin flipping from the -W(IV)(S=0)-CN-CoIII
      (S=0)- configuration to -W(V)(S=1/2)-CN-CoII (S=3/2)-.

PMID- 11512977
TI  - Ni phases formed in cement and cement systems under highly alkaline conditions:
      an XAFS study.
AB  - X-ray absorption fine structure (XAFS) spectroscopy was applied to assess the
      solubility-limiting phase of Ni in cement and cement minerals. The study reveals
      the formation Ni and Al containing hydrotalcite-like layered double hydroxides
      (Ni-Al LDHs) when cement material (a complex mixture of CaO, SiO2, Al2O3, Fe2O3
      and SO3) was treated with Ni in artificial cement pore water under highly
      alkaline conditions (pH = 13.3). This finding indicates that Ni-Al LDHs and not
      Ni-hydroxides determine the solubility of Ni in cement materials.

PMID- 11512978
TI  - In-situ EXAFS study of copper in the electrokinetic remediation process.
AB  - The speciation of copper in the early stage of the electrokinetic remediation
      (EKR) process has been studied by extended X-ray absorption fine structure
      (EXAFS) spectroscopy in the present work. By in-situ EXAFS, we found that copper
      in a contaminated soil possessed a Cu-O bond distance of 1.98 A with a
      coordination number (CN) of 5.8. In the second shell, the bond distance of Cu-(O)
      Cu was 2.87 A with a CN of 6.4. However, possibly due to the fact that incompact
      copper atoms in the outer shells were distorted by EKR, the Cu-(O)-Cu (2nd shell)
      bond distance and the CN of copper in the contaminated soil decreased by 0.08 A
      and 5.4, respectively in the early stage of the EKR process. Interestingly, after
      prolonging the contact time to about 80 minutes, the 1st-shell copper atoms were
      also perturbed by EKR. This work is an example of usefulness of the in-situ EXAFS
      spectroscopy for detailed studies of the speciation of copper in the contaminated
      soil during EKR process.

PMID- 11512979
TI  - Hole counts from X-ray absorption spectra.
AB  - The interpretation of X-ray absorption spectra in terms of electronic structure
      has long been of interest. Hole counts derived from such spectra are often
      interpreted in terms of free-atom occupation numbers or Mulliken counts. It is
      shown here, however, that renormalized-atom (RA) and cellular counts are better
      choices to characterize the configuration of occupied electron states in
      molecules and condensed matter. A projection-operator approach is introduced to
      subtract delocalized states and to determine quantitatively such hole counts from
      X-ray absorption spectra. The described approach is based on multiple-scattering
      theory (MST) and on atomic calculations of a smooth transformation relating the X
      ray absorption spectra to local projected densities of states (LDOS). Theoretical
      tests for the s and d electrons in transition metals show that the approach works
      well.

PMID- 11512980
TI  - X-ray absorption fine structure spectroscopy determination of the binding
      mechanism of tetrahedral anions to self assembled monolayers on mesoporous
      support.
AB  - X-ray absorption fine structure (XAFS) spectroscopy is used to investigate the
      chemical interaction between the end member [Cu(NH2)6] of self-assembled
      monolayers on mesoporous supports (SAMMS) and the tetrahedral anion SO4. The
      local structure about Cu indicates monodentate bonding between the SO4 anion and
      the SAMMS.

PMID- 11512981
TI  - Unexpected Fe local order in iron oxide coated nanocrystalline magnesium oxides
      with exceptional reactivities against environmental toxins.
AB  - Mg oxide nanoparticles are very reactive materials used to mitigate atmospheric
      pollution and to sequester polluting molecules. Using Fe K-edge XAFS, we have
      studied the structure of iron oxide-coated MgO nanoparticles before and after
      reaction with CCl4. Before reaction, the local structure around Fe is totally
      different from that in iron oxide coatings on SrO and CaO nanoparticles, although
      these coated materials were prepared in the same way. In SrO and CaO, the iron
      oxide coating has been shown to be well separated from the bulk of the
      nanoparticle, whereas in MgO, Fe was found to mix with MgO. After reaction with
      CCl4, Fe-Cl bonds can be detected when the coated nanoparticle is saturated. Such
      Fe-Cl EXAFS signals have not been observed in previously studied nanoparticles.

PMID- 11512982
TI  - Quick X-ray absorption spectroscopy for determining metal speciation in
      environmental samples.
AB  - We present a method for determining the chemical speciation of metals in
      environmental particles based on Quick-X-ray Absorption Spectroscopy. The
      approach can be applied to either the extended or the near edge fine structure,
      and consists in the decomposition of the XAS spectrum of an unknown sample on a
      reference set of standards' spectra using quadratic linear programming. The
      analysis accounts for the statistical experimental errors generated during the
      acquisition of X-ray absorption data, and leads to error estimates on the various
      fractions determined via a Monte Carlo procedure. An application example is
      presented for the speciation of inorganic Zn in a contaminated sediment sample.

PMID- 11512983
TI  - EXAFS study of copper in waste incineration fly ashes.
AB  - Copper species such as CuCO3, Cu(OH)2, CuS and CuO were found in the bag house
      and EP (electrostatic precipitator) fly ashes of waste incineration processes by
      X-ray absorption near edge structural (XANES) spectroscopy. A small amount of
      Cu(I) and metallic Cu was found in the bag house fly ash. The averaged Cu-O bond
      distance in the fly ashes determined by EXAFS (extended X-ray absorption fine
      structural) was 1.96 A with coordination numbers of 2.4-3.9. However, the Cu-(O)
      Cu (2nd shell) bond distance of the fly ashes in the incineration process was
      decreased by 0.19-0.21 A if compared to that of the CuO standard. The
      coordination numbers of the 2nd shell contribution to the bag house fly ash were
      not very significant.

PMID- 11512984
TI  - Oxygen 1s ELNES study of perovskites (Ca,Sr,Ba)TiO3.
AB  - The O K-edge spectra of perovskites XTiO3 with X=Ca, Sr and Ba have been measured
      using electron energy-loss spectroscopy (EELS) and are analyzed using the ab
      initio full multiple-scattering (MS) calculations. The near-edge structures arise
      mainly from covalency by direct and/or indirect interaction between oxygen and
      metal. The coordination number of the cation and the site symmetry also influence
      the spectral shape and structures. Comparison of full MS simulations of different
      clusters around the excited atom allows to interpret and correlate the features
      present in the spectra of each compound to its specific atomic arrangement and
      electronic structure.

PMID- 11512985
TI  - Anharmonic effective pair potentials of group VIII and lb fcc metals.
AB  - The temperature dependence of EXAFS Debye-Waller factors and anharmonic effective
      pair potentials of group VIII and Ib fcc metals were investigated by a cumulant
      expansion method. The EXAFS spectra near K- or L3-edges were measured at the
      temperatures from 30 to 800 K using synchrotron radiation from the Photon
      Factory, Tsukuba. The effective pair potentials, a x u2/2!+ b x u3/3! denote that
      the group Ib has obviously larger anharmonisity than the group VIII metals. The
      discrepancy between the Morse potential approximation and determined effective
      pair potential is discussed.

PMID- 11512986
TI  - Anharmonic effective pair potentials in CaTiO3, SrTiO3 and CaGeO3 perovskite.
AB  - The temperature dependence of EXAFS Debye-Waller factors in CaTiO3, SrTiO3 and
      CaGeO3 perovskite was investigated with the cumulant expansion method. The CaGeO3
      perovskite as an analogue of the Earth's lower-mantle mineral was synthesized in
      a cubic anvil type apparatus under 10 GPa 1250 K The Ca, Ti and Ge K-edge EXAFS
      spectra were measured in transmission mode at temperature up to 1100 K The
      effective pair potentials, V(u)= alpha (u2/2+ beta u3/3!, were evaluated and the
      Gruneisen parameter were calculated. The potential coefficients alpha and beta
      for Ti-O bond in CaTiO3 are 6.9 eVA(-2) and -38 eVA(-3), respectively. Those for
      Ge-O bond in CaGeO3 are 9.8 eVA(-2) and -36 eVA(-3), respectively.

PMID- 11512987
TI  - An EXAFS study of zinc coordination in microbial cells.
AB  - Five microbes were isolated from metal amended enrichment cultures derived from
      the sediments of a lake contaminated by a zinc smelter. Each of these organisms
      was grown in pure culture in the presence of zinc. Quick Extended X-ray
      Absorption Fine Structure (QEXAFS) spectroscopy was used to investigate the
      average coordination environment of the zinc associated with the microbial
      biomass. Fitting of the first coordination shell of zinc shows that significant
      differences exist for each microbial species examined. The coordination
      environment of zinc varies between sulfurs to six-fold nitrogen/oxygen. with two
      microbial strains showing mixed coordination shells. Further study is required in
      order to characterize these sites and their locations within the cell.

PMID- 11512988
TI  - XAFS determination of the bacterial cell wall functional groups responsible for
      complexation of Cd and U as a function of pH.
AB  - Bacteria, which are ubiquitous in near-surface geologic systems, can affect the
      distribution and fate of metals in these systems through adsorption reactions
      between the metals and bacterial cell walls. Recently, Fein et al. (1997)
      developed a chemical equilibrium approach to quantify metal adsorption onto cell
      walls, treating the sorption as a surface complexation phenomenon. However, such
      models are based on circumstantial bulk adsorption evidence only, and the nature
      and mechanism of metal binding to cell walls for each metal system have not been
      determined spectroscopically. The results of XAFS measurements at the Cd K-edge
      and U L3-edge on Bacillus subtilis exposed to these elements show that, at low
      pH, U binds to phosphoryl groups while Cd binds to carboxyl functional groups.

PMID- 11512989
TI  - XAS investigations of Fe(VI).
AB  - Recent attention has been given to a reexamination of results from the early
      Viking missions to Mars that suggested the presence of one or more strong
      oxidants in Martian soil. Since Fe is one of the main constituents of the Martian
      surface and Fe(VI) is known to be a highly reactive, strong oxidant, we have made
      XANES and EXAFS measurements of Fe(II), Fe(III), Fe(IV), and Fe(VI) in solid and
      solution forms. Results from these studies indicate a preedge XANES feature from
      Fe(VI) samples similar to that commonly seen from Cr(VI) samples. Results of
      first shell analysis indicate a linear relationship between the Fe-O bondlength
      and Fe valence state.

PMID- 11512990
TI  - Determination of the iron oxidation state in earth materials using XANES pre-edge
      information.
AB  - Fe K-edge XANES spectra have been measured in more than 35 Fe(II) and Fe(III)
      bearing minerals. The separation between the average pre-edge centroid positions
      for Fe(II) and Fe(III) is 1.4 +/- 0.1 eV. Examination of calculated pre-edge
      features of mechanical mixtures of phases containing different proportions of
      Fe(II) and Fe(III) reveals that different trends of pre-edge position vs. pre
      edge intensity can be observed, depending on the coordination environment. Both
      pre-edge parameters have been used to estimate the ferric/ferrous ratio in 12
      natural minerals.

PMID- 11512991
TI  - XANES analysis of sulfur form change during pyrolysis of coals.
AB  - Three kinds of coal and their density separated samples were rapidly pyrolyzed in
      a free-fall reactor under a nitrogen stream at a terminal temperature of 1253 K.
      X-ray absorption near edge structure analysis was applied to directly determine
      the sulfur forms in the coal and pyrolysis char. The results showed that the low
      density group contained sulfide and sulfoxide, which could contribute to the high
      extent of organic sulfur removal. Thermally stable thiophenic sulfur was observed
      in the higher density groups as a major form of organic sulfur.

PMID- 11512992
TI  - Identification of the chemical states of phosphorus in atmospheric aerosols by
      XANES spectrometry.
AB  - Depth selective XAFS spectrometry was applied to determine the chemical states of
      phosphorus in atmospheric aerosols. Atmospheric aerosols were collected on
      aluminum foils and polyethylene films using a 4-stage cascade impactor and a 12
      stage low pressure Andersen sampler, respectively. Samplings were performed at
      Uji (urban area) and Sakurajima (near a volcano). We measured X-ray fluorescence
      yield (XFY) and total electron yield (sample current) simultaneously to obtain
      the X-ray absorption near edge structure (XANES) spectra of the atmospheric
      aerosols. X-ray absorption in the vicinities of P K-edges was measured on the
      beamline BL-11B at the Photon Factory, High Energy Accelerator Research
      Organization, Tsukuba, Japan. The Sakurajima aerosol samples showed only a P5+
      peak and the peak was remarkable in coarse mode. In case of the Uji samples, the
      P5+ peak was dominant and a slight P3+ peak was detected for sample current
      measurement.

PMID- 11512993
TI  - EXAFS analysis using FEFF and FEFFIT.
AB  - Some of the advanced EXAFS analysis features of FEFF and FEFFIT are described.
      The scattering path formalism from FEFF and cumulant expansion are used as the
      basic building blocks of EXAFS analysis, giving a flexible and robust
      parameterization of most EXAFS problems. The ability to model EXAFS data in terms
      of generalized physical variables is shown, including the simultaneous refinement
      of two different polarizations for Co K EXAFS data of CoPt3.

PMID- 11512994
TI  - Speciation of As in the blackfoot disease endemic area.
AB  - Speciation of arsenic (As) in well water and contaminated soil in the blackfoot
      disease endemic area has been studied by extended X-ray absorption fine
      structural (EXAFS) spectroscopy in the present work. Experimentally, we found
      that arsenic in the well water possessed an As-O bond distance of 1.72 A with a
      coordination number (CN) of 4.3. In the blackfoot disease area, arsenic with a
      high oxidation state (As(V)) was also observed in the contaminated soil. In the
      early stage (after 90 minutes) of the electrokinetic remediation (EKR) of the
      contaminated soil, the in-situ EXAFS data indicated that the CN of As-O (1st
      shell) decreased slightly, that may be due to the perturbation of the incompact
      As atoms in the outer shells by EKR.

PMID- 11512995
TI  - Chromium speciation in residues after sequential extraction of a thermally
      treated sludge analog.
AB  - XANES fitting indicates that non-Cr2O3 form of Cr(III), transformed from CrO3 by
      four-hour heat application at 1100 degrees C, is the key species sorbed onto or
      lattice-diffused into kaolin matrices that exhibits strong leaching resistance to
      sequential extraction using various combined solutions including HNO3, H2O2, and
      HF. The EXAFS spectra are all in agreement with the XANES results. It is
      suggested that some Cr2O3 might have reacted with kaolin to form new compounds
      such as Cr2O3 x Al2O3 x 2SiO2 to account for the slight dissimilarity between the
      EXAFS spectra of samples and that of Cr2O3.

PMID- 11512996
TI  - Experimental and theoretical XANES study of the effects of Fe-Mg solid solution
      in the enstatite-ferrosilite series.
AB  - Synthetic orthopyroxenes in the join enstatite - ferrosilite (Mg2Si2O6-Fe2Si2O6)
      have been studied by XANES with the aim to interpret the variations found in the
      spectra and evaluate the effects of the Mg-Fe substitution in the orthopyroxene
      (OPX) structure. The experimental Fe- and Mg-K edge XANES spectra show variations
      of the peaks intensity as a function of the chemical composition of the samples
      along the EN-FS join. In the region of the Fe edge, the intensity ratio between
      peak A and B (IB/IA) varies linearly (R=0.99) with the Mg/Fe substitution.
      Multiple scattering calculation have been performed both at the Fe and Mg K-edge,
      to study the geometrical modifications of the M1 and M2 octahedral sites induced
      by the Mg-Fe substitutions. The spectra, obtained locating Fe (or Mg) in both M1
      and M2 and weighing the contributions using the occupancy data for the M1 and M2
      sites determined by XRD, allow to discriminate the effects to the total spectrum
      due to Fe (Mg) located in each sites separately.

PMID- 11512997
TI  - Studies on intake of heavy metals by Bradybaena similaris, land snails, by XAFS
      measurement.
AB  - We have applied XAFS in order to determine both the chemical form and the place
      where heavy metals are stored in cultivated land snails. From Cu and Zn XANES
      spectra, the shells showed similar patterns as those of soft tissues and not like
      carbonates. This indicates that heavy metals are not completely taken into
      carbonate structures but are present within organic components in the shells. In
      addition, Cu XANES spectra of the samples showed low absorption edge-energy in
      the order of hepatopancreas, mantle, body, and shell. By comparing samples with
      standard reagents, each of which has only S- or O-ligand, it was found that the
      metals in hepatopancreas exist mostly as S-bound chemical components. To quantify
      the relative abundance of S-bound chemical component, partial least-squares (PLS)
      regression was applied. The PLS result indicated that for Cu, S-bound compound
      was higher in the order of hepatopancreas > mantle > body >shell.

PMID- 11512998
TI  - Local structure of guest molecules in gas hydrates--a model study of Kr and Xe
      clathrates.
AB  - Gas hydrates constitute a class of solids in which small molecules occupy
      cavities inside an ice-like structure. There is enormous scientific and
      technological interest in understanding the structure, stability and formation
      mechanism of clathrates. We developed and constructed a variable temperature high
      pressure cell for x-rays measurements, which allows in situ studies of clathrate
      formation or decomposition. We used XAFS and Diffraction techniques to study the
      evolution of the structure during formation and decomposition. We studied two
      clathrates structures, structure I (Xe) and structure II (Kr). We were able to
      identify the local structure around the guest atom. We identified the rare gas
      water complexes that act as precursor to the formation of the crystalline phases.
      We observed the transformation of the clathrate from structure II to structure I
      when Xe is added to Kr clathrates.

PMID- 11512999
TI  - The zinc environment in Langmuir-Blodgett phospholipid multi-layers.
AB  - The Zinc environment of a system formed by Langmuir-Blodgett phospholipid multi
      layers is investigated by employing X-ray absorption spectroscopy. A comparative
      analysis of the Extended X-ray Absorption Fine Structure and Near Edge regions of
      the X-ray absorption spectra at the Zinc K-edge, in presence and in absence of
      the Myelin Basic Protein, clearly indicates that Zinc ions are bound to the heads
      of the phospholipidic molecules, while the presence of Myelin Basic Protein
      induces a visible distorsion of the geometry of the Zinc environment. These
      findings represent a first important step in understanding the interplay among
      the lipids of the myelin sheath, Myelin Basic Protein and Zinc, as Langmuir
      Blodgett phospholipid multi-layers represent a valuable model for the
      multilamellar structure of the membrane surrounding the nerve axon.

PMID- 11513000
TI  - Time-dependent XAS studies of trapped enzyme-substrate complexes of alcohol
      dehydrogenase from Thermoanaerobacter brockii.
AB  - The understanding of structure-function relationships in proteins has been
      significantly advanced with the advent of the biotechnological revolution. A goal
      yet to be realized for many metalloenzyme systems is to characterize the dynamic
      changes in structure that bridge the static endpoints provided by
      crystallography. We present here a series of edge and EXAFS spectra of the
      metalloenzyme alcohol dehydrogenase from Thermoanaerobacter brockii (TbADH)
      complexed with its substrate. The enzyme-substrate complexes were trapped by fast
      freezing at various times, following their enzyme activity. Our edge and EXAFS
      analyses both reveal the time-dependent changes in the structure of the active
      site of TbADH.

PMID- 11513001
TI  - XAFS in a single macrophage cell.
AB  - In this paper, a novel approach using XAFS will be introduced for the study of
      the problem of cytotoxicity of metal ions. A micro beam from a SR source was used
      to measure the time-dependent distributions and chemical states of elements in
      mouse macrophages that were cultured in metallic solutions of different
      concentration. It is revealed that the concentrations and distributions of
      calcium, zinc and potassium in a single cell are closely related to the uptake of
      the metal. Using XAFS analysis, it is shown that metal elements absorbed by the
      cell interact with the cell and that the chemical state of the metal is changed.

PMID- 11513002
TI  - XAS applied to pharmaceuticals: drug administration and bioavailability.
AB  - We present selected XAS applications, focused towards practical hospital
      questions of drug administration and bioavailability, where the technique is
      driven up to its limits of sensitivity. i) XAS was used to study the interactions
      between the components of parenteral nutrition solutions, in particular zinc and
      aminoacids, possibly modifying their bioavailability. ii) We studied by EXAFS a
      series of binary and ternary copper-aminoacid complexes, in view of the
      development of an efficient oral drug against copper deficiencies in Menkes
      disease. iii) EXAFS and XANES analysis allowed us to characterise the solution
      form of a new arsenic containing drug against leukaemia. In parallel to the XAS
      measurements, we analysed trace elements levels along patients' hairs, using X
      ray fluorescence excited by synchrotron radiation. The measurements along the
      hair allow for a monitoring of essential trace elements during therapy.

PMID- 11513003
TI  - A quasi-solid state electrochemical cell for in situ EXAFS measurements on
      biological samples.
AB  - A new "quasi-solid state" spectroelectrochemical cell for in-situ XAS
      measurements is described and tested using microperoxidase as reference material.
      The cell substantially improves conventional thin layer cells used for solution
      XAS spectroelectrochemistry in terms of assembling time and, more important,
      equilibration of the redox system under study with the applied potential. Spectra
      can be, in fact recorded simultaneously during a slow scan rate cyclic
      voltammetric scan thus permitting correlation of the spectra and the
      electrochemical curve. Other advantages are the possibility to use very small
      quantities of material also with second-generation rings. With high intensity
      sources having focussed beams a further decrease of the specimen weight can be
      easily obtained and the acquisition time of spectra further reduced.

PMID- 11513004
TI  - Zinc incorporation in human dental calculus.
AB  - We present here the first study of the local environment of zinc ions in
      biological calcium phosphates. It was suggested from in vitro studies that zinc
      inhibits the formation of hydroxyapatite and promotes the formation of more
      soluble phases, like tricalcium phosphate. Several mechanisms of zinc - calcium
      phosphate interaction were proposed, yielding either to the adsorption or to the
      incorporation of zinc ions into the phosphate structure. The results obtained
      here show that, under in vivo conditions, the zinc atoms are fully incorporated
      into the crystalline structure of the calcium phosphates.

PMID- 11513005
TI  - EXAFS analysis of the zinc-binding domain of boar spermatidal transition protein
      2.
AB  - Boar Spermatidal Transition Protein 2 (TP2; 137 amino acid residues) is supposed
      to play an important role in initiation of chromatin condensation and cessation
      of transcriptional activity during mammalian spermniogenesis. Boar TP2 has three
      potential zinc finger motifs and binds three atoms of zinc per molecule. However
      the structure of the zinc-binding domain of boar TP2 has not been completely
      determined. To elucidate the local structure around the zinc atoms of boar TP2,
      we performed an X-ray absorption fine structure (XAFS) measurement on the zinc
      binding domain of TP2(TP2Z)(residues 1-103) in the fluorescence mode. By EXAFS
      analyses we have demonstrated that each of the three zinc atoms is coordinated by
      approximately two sulfur and two nitrogen atoms on average. The average Zn-S and
      Zn-N distances were found to be 2.36 and 2.01 A, respectively. The sulfur and
      nitrogen atoms are attributed to cysteine and histidine residues, respectively,
      from comparison of the EXAFS spectra with model compounds ZnS and ZnTPP zinc(II)
      tetraphenylporphyrin).

PMID- 11513006
TI  - Determination of double decker sandwich structured La-substituted chlorophyll a
      by EXAFS.
AB  - As a representative natural porphyrin derivative, it is interesting to know the
      chemical form of lanthanide in chlorophyll a. We select the natural fern
      dicranopteris dichotoma, the most lanthanide-concentrated plant known, to isolate
      the chlorophyll a for our study. It is found by EXAFS that lanthanum substitutes
      in the magnesium position in chlorophyll and coordinates with the porphyrin ring.
      The lanthanum is seen to have a similar coordination structure to a sandwich-type
      lanthanide complex, with the La surrounded by eight nitrogen atoms from two
      porphyrin rings with average La-N bond length of 2.65 A.

PMID- 11513007
TI  - XANES spectroscopy of a single neuron from a patient with Parkinson's disease.
AB  - Chemical state of transition metals such as iron in a single neuron of the
      substantia nigra (SN) from a patient with Parkinson's disease (PD) was studied in
      this paper, using autopsy midbrain specimens including SN. Parkinson's disease is
      one of the major neurodegenerative diseases. The excessive accumulation of iron
      and its chemical states in SN neurons are related to the oxidative damage leading
      to neuronal cell death. X-ray absorption fine structure spectroscopy (XAFS) with
      SR micro beam (10 microm) was used to investigate the chemical state of iron in
      the SN neurons. X-ray absorption near-edge structure (XANES) spectroscopy results
      showed that the chemical state of iron in the neuromelanin granules within SN
      neurons changed from ferrous (Fe2+) to ferric (Fe3+) ion in the process of
      neuronal degeneration.

PMID- 11513008
TI  - Residential and nursing home care of elderly people with cognitive impairment:
      prevalence, mortality and costs.
AB  - Cognitive impairment among residents has considerable resource implications for
      both individuals and those responsible for publicly funded care. Two linked
      surveys were carried out in England: (1) a longitudinal study followed 2500
      admissions to publicly funded care up to 42 months after admission; and (2) a
      cross-sectional survey of 618 homes collected information about 11,900 residents.
      Information was collected about cognitive impairment using the Minimum Data Set
      Cognitive Performance Scale. Cognitive impairment was associated with source of
      funding and type of home. Although level of cognitive impairment has some effect,
      fees and costs were most influenced by type of home. At the same level of
      impairment, self-funded residents were more likely to be located in relatively
      low-cost settings than publicly funded residents. In independent homes fees were
      lower for publicly funded than for self-funded residents. Overall median length
      of stay of publicly funded admissions was 18 months. For the most part length of
      stay was not associated with level of cognitive impairment on admission. It is
      concluded that more information is needed about the effect of quality of care on
      people with cognitive impairment in different settings. If the same quality of
      care can be achieved in residential and nursing homes, the evidence would suggest
      that changes in placement policies could result in potential savings to the
      public purse.

PMID- 11513009
TI  - Financial strain and depressive symptoms in Hong Kong elderly Chinese: the
      moderating or mediating effect of sense of control.
AB  - For many Hong Kong Chinese elderly, depression and financial strain are quite a
      common occurrence. This study examines the mediating and moderating effect of
      sense of control in the relationship between financial strain and depressive
      symptoms. The data came from a survey of a representative community sample of 411
      elderly respondents in Hong Kong. Using multiple regression models, the authors
      found that generalized sense of control mediated and moderated the linkage
      between financial strain and depressive symptoms even after controlling socio
      demographic variables but sense of control over finances did not. Findings
      suggest that generalized sense of control should be enhanced to protect older
      people under chronic financial strain from depression.

PMID- 11513010
TI  - Cross-cultural comparability of the Geriatric Depression Scale: comparison
      between older Koreans and older Americans.
AB  - It is becoming increasingly clear that, in order to better understand the
      implications of global aging, more cross-cultural research is needed. In the
      present study, the structure and validity of the Geriatric Depression Scale-Short
      Form (GDS-SF) was examined in Korean and US samples of older adults. The
      participants included 153 older adults living in Korea (mean age=65.9 years) and
      459 older adults from Florida (mean age=72.4 years). All participants completed
      the original or translated versions of the GDS-SF, as well as additional
      demographic and health-related measures. The results indicated that the GDS-SF
      exhibited good reliability in both samples. However, the results of a principal
      components analysis indicated that the structure was not well replicated across
      the two samples. In general, the present study suggests that, despite great
      efforts to make the questionnaires equivalent in the two cultures, the concept of
      depression for older adults may vary greatly in Korea and the USA. Possible
      explanations for cross-cultural differences are discussed, as well as
      implications.

PMID- 11513011
TI  - Interrater reliability of the Physical Self-Maintenance Scale and the
      Instrumental Activities of Daily Living Scale in a variety of health professional
      representatives.
AB  - This study was performed to assess interrater reliability of the Japanese version
      of the Physical Self-Maintenance Scale (PSMS) and the Instrumental Activities of
      Daily Living Scale (IADL), which are simple and efficient assessment instruments
      of functional abilities in elderly patients. The subjects were 25 consecutive
      patients with Alzheimer's disease who were outpatients of the Department of
      Neuropsychiatry in Ehime University School of Medicine and their principal
      caregivers. One neuropsychiatrist administered the PSMS and IADL, and all
      sessions were videotaped. Then one clinical psychologist, one public health nurse
      and one neurologist, and one occupational therapist from another institution,
      viewed the videotape and performed reassessments. All interrater reliabilities
      between the neuropsychiatrist and the neurologist, the public health nurse, the
      clinical psychologist and the occupational therapist were extremely good.
      Interrater reliability between the public health nurse and the clinical
      psychologist, between the clinical psychologist and the neurologist and between
      the public health nurse and the neurologist was also extremely good. The PSMS and
      IADL showed good interrater reliability between personnel from different
      disciplines. They are likely to be useful tests for everyday medical
      consultations and for field research.

PMID- 11513012
TI  - Death from anorexia nervosa: age span and sex differences.
AB  - The purpose of this study was to assess characteristics of individuals who died
      from anorexia nervosa by assessing the frequency with which anorexia nervosa is
      listed as a causal factor related to the death of individuals in the USA. Data
      from over 10 million death records (all National Center for Health Statistic
      registered deaths in the USA for 1986-90) were examined for mention of anorexia
      nervosa as a primary or contributing cause of death. Only 724 were found, which
      equals an average of 145 annual deaths, and a rate of 6.73 per 100,000 deaths.
      The age and sex distribution suggests two fatal forms of anorexia nervosa, an
      early-onset form comprising 89% women and a later form comprising 24% men. The
      findings suggest that the mortality risk from current anorexia nervosa may be
      lower than formerly supposed and that it is not confined to young adults and
      adolescents.

PMID- 11513013
TI  - The structure of subjective well-being in middle adulthood.
AB  - Subjective well-being (SWB) is at the centre of much ageing research due to its
      relationship to such important outcomes as health, morbidity and successful
      ageing. This paper discusses essential problems associated with its definition,
      measurement and dimensionality. Exploratory and confirmatory factor analyses were
      computed for data from the Interdisciplinary Longitudinal Study of Adult
      Development in order to assess whether SWB is a unidimensional or a
      multidimensional construct. The results suggest that SWB is unidimensional.

PMID- 11513014
TI  - Providing education about Alzheimer's disease.
AB  - Improving carers' knowledge of Alzheimer's disease (AD) has been associated with
      benefits for carer well-being. This has led to recognition of the need to
      systematically evaluate dementia education tools. In this study dementia
      knowledge was measured before and after interventions designed to improve
      knowledge in a sample of 100 undergraduate students. Dementia education materials
      were selected from existing resources that are readily accessible and are
      recommended for use in clinical settings. Subjects were allocated to one of four
      conditions, including a control group. Subjects allocated to education conditions
      were asked to view a video on AD, read written information about the disease or
      do both. Results showed that education improved knowledge of AD, as measured by
      increased scores on a dementia knowledge questionnaire. This study has important
      implications for public education about dementia and resource allocation for
      service providers.

PMID- 11513015
TI  - Risk factor characteristics in carers who physically abuse or neglect their
      elderly dependants.
AB  - This study investigates the prevalence of, and differences in, risk factor
      characteristics in a sample of two select populations of carers, one of which
      physically abused their elderly dependants and one of which neglected them.
      Nineteen carers (nine who had physically abused and 10 who had neglected their
      elderly relatives), who were referred to clinical psychology by either their
      general practitioner or their psychiatrist, were invited to take part in this
      study. A detailed history of risk factors was obtained, including history of
      alcohol dependency, type and history of mental ill health, history of
      maltreatment earlier in life, who they were caring for, how long they had been a
      carer and whether they felt isolated as a carer. Subjects were then given five
      assessments to determine whether there were any differences between the two
      groups. These were the Conflict Tactic Scale, Strain Scale, Beck Depression
      Inventory, Beck Anxiety Inventory and Cost of Care Index. An examination of the
      risk factors suggests that heavy alcohol consumption and past childhood abuse by
      fathers were likely to lead to physical abuse. Significantly higher conflict and
      depression scores were also present in the physical abuse group, while the
      neglect group had significantly higher anxiety scores. It is suggested that these
      findings should be incorporated into an assessment of future risk of abuse or
      neglect by the carer.

PMID- 11513016
TI  - A multi-method evaluation of an independent dementia care service and its
      approach.
AB  - Changes to approaches in dementia care and subsequent services over the last
      decade have meant that quality of care for people with dementia and their carers
      has undoubtedly improved. However, few in-depth dementia service evaluation
      studies are documented. Those that are tend to focus on traditional evaluation
      measures such as length of stay or functional improvement, or they concentrate on
      the perspectives of carers. This study used multiple methods within Fourth
      Generation Methodology to evaluate (SPECAL) Specialized Early Care of
      Alzheimer's, a dementia care service and approach. The findings demonstrated
      that, within its approach, there was high quality of care offered by SPECAL to
      people with dementia and their carers. The evaluation also highlighted some of
      the difficulties facing SPECAL in its relationships with existing professional
      providers of mental health care for older people that have implications for other
      service providers. Recommendations from the evaluation were adopted as an agenda
      for future developmental work. This study has provoked broader questions for
      multi-disciplinary and multi-agency teams about quality of services for older
      people with dementia, and about relationships between the voluntary and statutory
      sectors.

PMID- 11513017
TI  - Alcohol expectancies and their relationship to alcohol use: age and sex
      differences.
AB  - Previous studies have demonstrated a correlation between expectancies that
      adolescents and young adults hold about the effects of alcohol and the amount of
      alcohol they consume. This study examined age and sex differences in expectancies
      and alcohol consumption in a sample of 92 older and 83 younger adults. The two
      groups were administered self-report questionnaires for quantity and frequency of
      alcohol consumption, and for positive and negative expectancies regarding the
      effects of alcohol. Results found lower quantities of alcohol consumption per
      occasion in older adults, but higher frequency of drinking occasions. Older
      adults reported significantly lower levels of both positive and negative
      expectancies when compared with the younger sample. Among older women, regression
      analyses found a significant relationship between negative expectancies and lower
      alcohol consumption. For older men, positive expectancies showed a positive
      relationship to consumption, while negative expectancies showed a negative
      relationship to consumption. For younger women, positive expectancies were
      related to increased consumption. These findings suggest different strategies
      based on age and sex in treatment models, which identify expectancies as
      important components of drinking behavior.

PMID- 11513018
TI  - Negative life events and depressive symptoms in the elderly: a life span
      perspective.
AB  - This study suggests that negative life events may have long-term consequences for
      people's well-being. A community sample of 194 elderly people was interviewed by
      means of the Geriatric Depression Scale and the Negative Life Events
      Questionnaire. Depressed mood at old age was related to the reporting of negative
      socio-economic circumstances as well as emotional abuse and neglect during
      childhood, and to the reporting of negative socio-economic circumstances, sexual
      abuse, emotional abuse and neglect, relational stress and problem behaviour of
      significant others during (late) adulthood. Depression scores were especially
      high when subjects reported the experience of many events during adulthood and
      late adulthood. On top of this, the interaction effect between the number of
      negative life events experienced in childhood and adulthood indicated that there
      was a much stronger association between the number of negative life events
      experienced in adulthood and depressive symptoms in late life, for those who
      experienced more negative life events in childhood, than for those who did not.
      It is suggested that incorporating life histories into the diagnostic interview
      is advisable.

PMID- 11513019
TI  - The use of applied tension and cognitive therapy to manage syncope (common faint)
      in an older adult.
AB  - The rationale for the use of the applied tension technique in the treatment of
      syncope (common faint) is outlined. A case example of its successful use in
      combination with cognitive therapy for anxiety in an appropriately screened older
      person is provided.

PMID- 11513020
TI  - Automated segmentation of multiple sclerosis lesions by model outlier detection.
AB  - This paper presents a fully automated algorithm for segmentation of multiple
      sclerosis (MS) lesions from multispectral magnetic resonance (MR) images. The
      method performs intensity-based tissue classification using a stochastic model
      for normal brain images and simultaneously detects MS lesions as outliers that
      are not well explained by the model. It corrects for MR field inhomogeneities,
      estimates tissue-specific intensity models from the data itself, and incorporates
      contextual information in the classification using a Markov random field. The
      results of the automated method are compared with lesion delineations by human
      experts, showing a high total lesion load correlation. When the degree of spatial
      correspondence between segmentations is taken into account, considerable
      disagreement is found, both between expert segmentations, and between expert and
      automatic measurements.

PMID- 11513021
TI  - Artery-vein separation via MRA--an image processing approach.
AB  - This paper presents a near-automatic process for separating vessels from
      background and other clutter as well as for separating arteries and veins in
      contrast-enhanced magnetic resonance angiographic (CE-MRA) image data, and an
      optimal method for three-dimensional visualization of vascular structures. The
      separation process utilizes fuzzy connected object delineation principles and
      algorithms. The first step of this separation process is the segmentation of the
      entire vessel structure from the background and other clutter via absolute fuzzy
      connectedness. The second step is to separate artery from vein within this entire
      vessel structure via iterative relative fuzzy connectedness. After seed voxels
      are specified inside artery and vein in the CE-MRA image, the small regions of
      the bigger aspects of artery and vein are separated in the initial iterations,
      and further detailed aspects of artery and vein are included in later iterations.
      At each iteration, the artery and vein compete among themselves to grab
      membership of each voxel in the vessel structure based on the relative strength
      of connectedness of the voxel in the artery and vein. This approach has been
      implemented in a software package for routine use in a clinical setting and
      tested on 133 CE-MRA studies of the pelvic region and two studies of the carotid
      system from six different hospitals. In all studies, unified parameter settings
      produced correct artery-vein separation. When compared with manual
      segmentation/separation, our algorithms were able to separate higher order
      branches, and therefore produced vastly more details in the segmented vascular
      structure. The total operator and computer time taken per study is on the average
      about 4.5 min. To date, this technique seems to be the only image processing
      approach that can be routinely applied for artery and vein separation.

PMID- 11513022
TI  - Specified-resolution wavelet analysis of activation patterns from BOLD contrast
      fMRI.
AB  - Functional magnetic resonance (MR) MR imaging (fMRI) with blood-oxygenation-level
      dependent (BOLD) contrast localizes neuronal processing of cognitive paradigms.
      As magnetic resonance signal responses are small, functional mapping requires
      statistical analysis of temporally averaged image data. Although voxels
      activating at the paradigm frequency can be identified from the Fourier power
      spectrum, such analyses collapse the temporal information that is useful to
      establish consistency of responses during the paradigm. The design of a set of
      nonorthogonal wavelets of specified frequency resolution within the power
      spectrum was investigated for extracting desired frequency responses from the
      noisy signal intensity of individual voxels. These wavelets separate the low
      frequency cognitive response to the paradigm from the respiratory and cardiac
      responses at higher frequencies. The retention of the temporal information,
      possible by wavelet analysis, allows the MR signal changes to be compared to
      changes in behavioral responses over the duration of an entire paradigm. The
      amplitude and time delay of the wavelet specified by the paradigm identify
      quantitatively the size of the MR signal change and the temporal delay of the
      hemodynamic BOLD response, respectively. This specified-resolution wavelet
      analysis was demonstrated for individual voxels and maps through the frontal eye
      fields using a visually guided saccade paradigm.

PMID- 11513023
TI  - Computer-assisted bone age assessment: image preprocessing and
      epiphyseal/metaphyseal ROI extraction.
AB  - Clinical assessment of skeletal maturity is based on a visual comparison of a
      left-hand wrist radiograph with atlas patterns. Using a new digital hand atlas an
      image analysis methodology is being developed. To assist radiologists in bone age
      estimation. The analysis starts with a preprocessing function yielding
      epiphyseal/metaphyseal regions of interest (EMROIs). Then, these regions are
      subjected to a feature extraction function. Accuracy has been measured
      independently at three stages of the image analysis: detection of phalangeal tip,
      extraction of the EMROIs, and location of diameters and lower edge of the EMROIs.
      Extracted features describe the stage of skeletal development more objectively
      than visual comparison.

PMID- 11513024
TI  - Analytic determination of pinhole collimator sensitivity with penetration.
AB  - Pinhole collimators are widely used to image small organs and animals. The
      sensitivity of knife-edge pinhole collimators has been previously estimated using
      an "effective diameter" formulation and experimentally described using a sin(x)
      theta fit, where theta is the angle between the line segment from the center of
      the aperture to the photon source and its projection onto the plane of the
      aperture. An analytic form of the sensitivity of the pinhole collimator is
      derived in this paper. A numerical formula for predicting the sin(x) theta form
      of the sensitivity is calculated from the analytic form. Experimental data are
      compared with the theoretical estimate and the sin(x) theta prediction. The
      agreement is excellent.

PMID- 11513025
TI  - Comparison of algorithms for combining X-ray angiography images.
AB  - Using a one-dimensional convective-dispersive model of contrast agent flow in a
      blood vessel, we optimized and compared algorithms for combining a temporal
      sequence of X-ray angiography images, each with incomplete arterial filling, into
      a single-output image with fully opacified arteries. The four algorithms were:
      maximum opacity (MO) with a maximum over time at each spatial location; matched
      filtering (MAT); recursive filtering (REC) with a maximum opacity; and an
      approximate matched filter (AMF) consisting of a correlation with a kernel that
      approximates the matched filter kernel followed by a maximum opacity operation.
      Based on the contrast-to-noise ratio (CNR), MAT is theoretically the best
      algorithm. However, with spatially varying clinical images, a poorly matched MAT
      kernel greatly degraded CNR to the point of even inverting artery contrast. The
      practical AMF method maintained uniform CNR values over the entire field of view
      and gave >90% of the theoretical limit set by MAT. REC and MO created fully
      opacified arteries, but provided little CNR enhancement. By holding CNR at a
      nominal reference value, simulations predicted that AMF could be used with a
      contrast agent volume reduced by as much as 66%. Alternatively, X-ray exposure
      rate could be lowered. Although MO and REC are more easily implemented, the
      contrast enhancement with AMF makes it attractive for processing diagnostic
      angiography images acquired with a reduced contrast agent dose.

PMID- 11513026
TI  - Validation of ultrasonic image boundary recognition in abdominal aortic aneurysm.
AB  - An aneurysm of the abdominal aorta (AAA) is characterized by modified wall
      properties, and a balloon-like area usually filled by a thrombus. A rupture of an
      aortic aneurysm can be fatal, yet there is no way to accurately predict such an
      occurrence. The study of the wall and thrombus cross-sectional distension, due to
      a pressure wave, is important as a way of assessing the degradation of the
      mechanical properties of the vessel wall and the risk of a rupture. Echo
      ultrasound transverse cross-sectional imaging is used here to study the thrombus
      and the aortic wall distension, requiring their segmentation within the image.
      Polar coordinates are defined, and a search is performed for minimizing a cost
      function, which includes a description of the boundary (based on a limited series
      of sine and cosine functions) and information from the image intensity gradients
      along the radii. The method is based on filtering by a modified Canny-Deriche
      edge detector and then on minimization of an energy function based on five parts.
      Since echoes from blood in the lumen and the thrombus produce similar patterns
      and speckle noise, a modified version for identifying the lumen-thrombus border
      was developed. The method has been validated by various ways, including parameter
      sensitivity testing and comparison to the performance of an expert. It is robust
      enough to track the lumen and total arterial cross-sectional area changes during
      the cardiac cycle. In 34 patients where sequences of images were acquired, the
      border between the thrombus and the arterial wall was detected with errors less
      than 2%, while the lumen-thrombus border was detected with a mean error of 4%.
      Thus, a noninvasive measurement of the AAA cross-sectional area is presented,
      which has been validated and found to be accurate.

PMID- 11513027
TI  - Frequency decomposition and compounding of ultrasound medical images with wavelet
      packets.
AB  - Ultrasound beams propagating in biological tissues undergo distortions due to
      local inhomogeneities of the acoustic parameters and the nonlinearity of the
      medium. The spectral analysis of the radio-frequency (RF) backscattered signals
      may yield important clinical information in the field of tissue characterization,
      as well as enhancing the detectability of tissue parenchymal diseases. In this
      paper, we propose a new tissue spectral imaging technique based on the wavelet
      packets (WP) decomposition. In a conventional ultrasound imaging system, the
      received echo-signals are generally decimated to generate a medical image, with a
      loss of information. With the proposed approach, all the RF data are processed to
      generate a set of frequency subband images. The ultrasound echo signals are
      simultaneously frequency decomposed and decimated, by using two quadrature mirror
      filters, followed by a dyadic subsampling. In addition, to enhance the lesion
      detectability and the image quality, we apply a nonlinear filter to reduce noise
      in each subband image. The proposed method requires simple additional signal
      processing and it can be implemented on any real-time imaging system. The
      frequency subband images, which are available simultaneously, can be either used
      in a multispectral display or summed up together to reduce speckle noise. To
      localize the different frequency response in the tissues, we propose a
      multifrequency display method where three different subband images, chosen among
      those available, are encoded as red, green, and blue intensities (RGB) to create
      a false-colored RGB image. According to the clinical application, different
      choices can evidence different spectral proprieties in the biological tissue
      under investigation. To enhance the lesion contrast in a grey-level image, one of
      the possible methods is the summation of the images obtained from narrow
      frequency subbands, according to the frequency compounding technique. We show
      that by adding the denoised subband images created with the WP decomposition, the
      contrast-to-noise ratio in two phantom images is largely increased.

PMID- 11513028
TI  - Novel Bayesian multiscale method for speckle removal in medical ultrasound
      images.
AB  - A novel speckle suppression method for medical ultrasound images is presented.
      First, the logarithmic transform of the original image is analyzed into the
      multiscale wavelet domain. We show that the subband decompositions of ultrasound
      images have significantly non-Gaussian statistics that are best described by
      families of heavy-tailed distributions such as the alpha-stable. Then, we design
      a Bayesian estimator that exploits these statistics. We use the alpha-stable
      model to develop a blind noise-removal processor that performs a nonlinear
      operation on the data. Finally, we compare our technique with current state-of
      the-art soft and hard thresholding methods applied on actual ultrasound medical
      images and we quantify the achieved performance improvement.

PMID- 11513029
TI  - Authenticity and integrity of digital mammography images.
AB  - Data security becomes more and more important in telemammography which uses a
      public high-speed wide area network connecting the examination site with the
      mammography expert center. Generally, security is characterized in terms of
      privacy, authenticity and integrity of digital data. Privacy is a network access
      issue and is not considered in this paper. We present a method, authenticity and
      integrity of digital mammography, here which can meet the requirements of
      authenticity and integrity for mammography image (IM) transmission. The
      authenticity and integrity for mammography (AIDM) consists of the following four
      modules. 1) Image preprocessing: To segment breast pixels from background and
      extract patient information from digital imaging and communication in medicine
      (DICOM) image header. 2) Image hashing: To compute an image hash value of the
      mammogram using the MD5 hash algorithm. 3) Data encryption: To produce a digital
      envelope containing the encrypted image hash value (digital signature) and
      corresponding patient information. 4) Data embedding: To embed the digital
      envelope into the image. This is done by replacing the least significant bit of a
      random pixel of the mammogram by one bit of the digital envelope bit stream and
      repeating for all bits in the bit stream. Experiments with digital IMs
      demonstrate the following. 1) In the expert center, only the user who knows the
      private key can open the digital envelope and read the patient information data
      and the digital signature of the mammogram transmitted from the examination site.
      2) Data integrity can be verified by matching the image hash value decrypted from
      the digital signature with that computed from the transmitted image. 3) No visual
      quality degradation is detected in the embedded image compared with the original.
      Our preliminary results demonstrate that AIDM is an effective method for image
      authenticity and integrity in telemammography application.

PMID- 11513030
TI  - Breast tissue density quantification via digitized mammograms.
AB  - Studies reported in the literature indicate that breast cancer risk is associated
      with mammographic densities. An objective, repeatable, and a quantitative measure
      of risk derived from mammographic densities will be of considerable use in
      recommending alternative screening paradigms and/or preventive measures. However,
      image processing efforts toward this goal seem to be sparse in the literature,
      and automatic and efficient methods do not seem to exist. In this paper, we
      describe and validate an automatic and reproducible method to segment dense
      tissue regions from fat within breasts from digitized mammograms using scale
      based fuzzy connectivity methods. Different measures for characterizing
      mammographic density are computed from the segmented regions and their robustness
      in terms of their linear correlation across two different projections--cranio
      caudal and medio-lateral-oblique--are studied. The accuracy of the method is
      studied by computing the area of mismatch of segmented dense regions using the
      proposed method and using manual outlining. A comparison between the mammographic
      density parameter taking into account the original intensities and that just
      considering the segmented area indicates that the former may have some advantages
      over the latter.

PMID- 11513031
TI  - Comparison of 3-D reconstruction with 3D-OSEM and with FORE+OSEM for PET.
AB  - The combination of Fourier rebinning (FORE) and the ordered subsets expectation
      maximization (OSEM), a fast statistical algorithm, appears as a promising
      alternative to the fully three-dimensional (3-D) iterative approach for clinical
      positron emission tomography (PET) data. In this paper, we evaluated the
      properties of FORE+OSEM and compared it with fully 3-D OSEM using both
      simulations and data acquired by commercial scanners. The aim is to determine to
      what extent the speed advantage of FORE+OSEM is paid for by a possible
      degradation of image quality in the case of noisy clinical PET data. A forward-
      and back-projection pair based on a line integral model was used in two
      dimensional OSEM and 3-D OSEM (3D-OSEM) instead of a system matrix. Different
      variants of both approaches have been studied with simulations in terms of
      contrast-noise tradeoff. Two variants--FORE+OSEM with attenuation weighting (AW)
      [FORE+OSEM(AW)] and 3D-OSEM with attenuation-normalization weighting (ANSP) and a
      shifted-Poisson (SP) model [3D-OSEM(ANSP)]--were compared with measured phantom
      data and patient data. Based on the results from both simulations and measured
      data, we conclude that: 1) both attenuation (-normalization) weighting and the SP
      model improve the image quality but slow down the convergence and 2) despite its
      approximate nature, FORE+OSEM does not show apparent image degradation compared
      with 3D-OSEM for data with a noise level typical of a whole-body FDG scan.

PMID- 11513032
TI  - Theoretical study of lesion detectability of MAP reconstruction using computer
      observers.
AB  - The low signal-to-noise ratio (SNR) in emission data has stimulated the
      development of statistical image reconstruction methods based on the maximum a
      posteriori (MAP) principle. Experimental examples have shown that statistical
      methods improve image quality compared to the conventional filtered
      backprojection (FBP) method. However, these results depend on isolated data sets.
      Here we study the lesion detectability of MAP reconstruction theoretically, using
      computer observers. These theoretical results can be applied to different object
      structures. They show that for a quadratic smoothing prior, the lesion
      detectability using the prewhitening observer is independent of the smoothing
      parameter and the neighborhood of the prior, while the nonprewhitening observer
      exhibits an optimum smoothing point. We also compare the results to those of FBP
      reconstruction. The comparison shows that for ideal positron emission tomography
      (PET) systems (where data are true line integrals of the tracer distribution) the
      MAP reconstruction has a higher SNR for lesion detection than FBP reconstruction
      due to the modeling of the Poisson noise. For realistic systems, MAP
      reconstruction further benefits from accurately modeling the physical photon
      detection process in PET.

PMID- 11513033
TI  - New techniques for efficient sliding thin-slab volume visualization.
AB  - High-resolution three-dimensional (3-D) volumetric images obtained by today's
      radiologic imaging scanners are rich in detailed diagnostic information. Despite
      the many visualization techniques available to assess such images, there remains
      information that is challenging to uncover, such as the location of small
      structures (e.g., mediastinal lymph nodes, narrowed-airway regions). Recently,
      sliding thin-slab (STS) visualization was proposed to improve the visualization
      of interior structures. These STS techniques sometimes depend on user opacity
      specifications or extra preprocessing, and other rendering approaches that use
      the general STS mechanism are conceivable. We introduce two techniques for STS
      volume visualization. The first, a depth (perspective) rendering process,
      produces an unobstructed, high-contrast 3-D view of the information within a thin
      volume of image data. Results are a function of relative planar locations. Thus,
      rendered views accurately depict the internal properties that were initially
      captured as position and intensity. The second method produces a gradient-like
      view of the intensity changes in a thin volume. Results can effectively detect
      the occurrence and location of dramatic tissue variations, often not visually
      recognized otherwise. Both STS techniques exploit the concept of temporal
      coherence to form sequences of consecutive slabs, using information from
      previously computed slabs. This permits efficient real-time computation on a
      general-purpose computer. Further, these techniques require no preprocessing, and
      results are not dependent on user knowledge. Results using 3-D computed
      tomography chest images show the computational efficiency and visual efficacy of
      the new STS techniques.

PMID- 11513034
TI  - A framework for predictive modeling of anatomical deformations.
AB  - A framework for modeling and predicting anatomical deformations is presented, and
      tested on simulated images. Although a variety of deformations can be modeled in
      this framework, emphasis is placed on surgical planning, and particularly on
      modeling and predicting changes of anatomy between preoperative and
      intraoperative positions, as well as on deformations induced by tumor growth. Two
      methods are examined. The first is purely shape-based and utilizes the principal
      modes of co-variation between anatomy and deformation in order to statistically
      represent deformability. When a patient's anatomy is available, it is used in
      conjunction with the statistical model to predict the way in which the anatomy
      will/can deform. The second method is related, and it uses the statistical model
      in conjunction with a biomechanical model of anatomical deformation. It examines
      the principal modes of co-variation between shape and forces, with the latter
      driving the biomechanical model, and thus predicting deformation. Results are
      shown on simulated images, demonstrating that systematic deformations, such as
      those resulting from change in position or from tumor growth, can be estimated
      very well using these models. Estimation accuracy will depend on the application,
      and particularly on how systematic a deformation of interest is.

PMID- 11513035
TI  - A bound on mutual information for image registration.
AB  - An upper bound is derived for the mutual information between a fixed image and a
      deformable template containing a fixed number of gray-levels. The bound can be
      calculated by maximizing the entropy of the template under the constraint that
      the conditional entropy of the template, given the fixed image, be zero. This
      bound provides useful insight into the properties of mutual information as a
      similarity metric for deformable image registration. Specifically, it indicates
      that maximizing mutual information may not necessarily produce an optimal
      solution when the deformable transform is too flexible.

PMID- 11513036
TI  - Novel reduced benzo[j]fluranthen-3-ones from Cladosporium cf. cladosporioides
      with cytokine production and tyrosine kinase inhibitory properties.
AB  - A series of reduced benzo[j]fluoranthen-3-ones (1-4) was isolated from
      fermentations of a fungal strain CBUK20700 (CBS 100220), classified as
      Cladosporium cf. cladosporioides, during a microbial extract screening programme
      to identify inhibitors of anti-CD28-induced interleukin-2 (IL-2) production by
      Jurkat E6-1 cells as potential immunosuppressive agents. These compounds were
      also found to be tyrosine kinase inhibitors. The structures of compounds 1-4 were
      elucidated by spectroscopic methods including the HMQC, HMBC and NOESY NMR
      experiments. The most potent compound in the series, (6bS,7R,8S)-7-methoxy-4,8,9
      trihydroxy-1,6b,7,8-tetrahydro-2H-benzo[j]fluoranthen-3-one (1) inhibited anti
      CD28-induced IL-2 production and Abl tyrosine kinase with IC50 values of 400 and
      60 nM respectively. The 6b-stereoisomeric 2 was a moderate inhibitor of both IL-2
      production and Abl tyrosine kinase while the 8-oxo derivative 3 was inactive in
      both assays. The 8-O-methyl ether 4 was a moderate inhibitor of IL-2 production
      but exhibited potent inhibition of Abl tyrosine kinase with an IC50 of 45 nM.

PMID- 11513037
TI  - F13459, a new derivative of mycophenolic acid. I. Taxonomy, isolation, and
      biological properties.
AB  - In the course of screening for inhibitors of intracellular trafficking of
      glycoprotein, a new inhibitor, F13459 was isolated from the culture broth of a
      Penicillium sp. It was purified using solvent extraction, silica gel, Sephadex LH
      20 and ODS column chromatography. From structural analysis, F13459 was a
      derivative of mycophenolic acid, an inhibitor of inosine 5'-monophosphate
      dehydrogenase. F13459 inhibited hemagglutinin synthesis of NDV at concentrations
      more than 25 microg/ml. However, syncytium formation as a result of cell surface
      expression of F-glycoprotein of NDV was inhibited at concentrations of F13459
      lower than those required for appreciable inhibition of glycoprotein synthesis.

PMID- 11513038
TI  - F13459, a new derivative of mycophenolic acid. II. Physico-chemical properties
      and structural elucidation.
AB  - F13459 is a new inhibitor of synthesis and trafficking of virus glycoprotein
      isolated from the culture broth of a Penicillium sp. The molecular formula of
      F13459 was determined to be C27H28O11 by HRFAB-MS and NMR spectral analyses. The
      structure of F13459 was elucidated to be 3,4-dihydro-3,4,6,8-tetrahydroxy-3
      methyl-1H-2-benzopyran-1-one 4-O-mycophenolate, an ester derivative of
      mycophenolic acid. F13459 was isolated as the optically inactive form. F13459
      exists in epimeric mixtures at C-3' through relatively fast hemiacetal-ketone
      tautomerism and at C-4' through slow keto-enol tautomerism. Those epimerizations
      were confirmed by NOE differential experiments for fast chemical exchange and
      equilibrium and by deuteration experiments in NMR for slow chemical exchange.

PMID- 11513039
TI  - Association of induced disease resistance of rhododendron seedlings with
      inoculation of Streptomyces sp. R-5 and treatment with actinomycin D and
      amphotericin B to the tissue-culture medium.
AB  - Seedlings of rhododendron were treated by adding Streptomyces sp. strain R-5,
      actinomycin D and/or amphotericin B to the tissue-culture medium. HPLC analysis
      showed that all of the treated seedlings contained these antibiotics at
      concentrations higher than the suppressive levels to mycelial growth of
      Pestalotiopsis sydowiana, a major pathogen of rhododendron. Occurrence of disease
      caused by this fungus in the seedlings was suppressed by treatment of the medium
      surface with strain R-5, but not by treatment with these antibiotics, suggesting
      that growth of strain R-5, an antibiotic producer, could be essential for
      induction of disease resistance in tissue-cultured seedlings of rhododendron.

PMID- 11513040
TI  - 3-Keto-9-O-substituted oxime derivatives of 6-O-methyl erythromycin A synthesis
      and in vitro activity.
AB  - A series of 3-keto-9-O-substituted oxime derivatives of 6-O-methyl erythromycin A
      were prepared with a novel synthetic route, which include 6 reaction steps-
      oximation, protection, hydrolysis, oxidation, deprotection and addition. The
      antibacterial activity of these compounds were tested in vitro against both
      erythromycin-susceptible and erythromycin-resistant organisms. Several of these
      derivatives showed improved antibacterial activity against some erythromycin
      resistant organisms as compared to erythromycin A.

PMID- 11513041
TI  - New inhibitors of 3alpha-hydroxysteriod dehydrogenase, 0231A and 0231B from
      Streptomyces sp. HKI 0231.

PMID- 11513042
TI  - Benzastatins H and I, new benzastatin derivatives with neuronal cell protecting
      activity from Streptomyces nitrosporeus.

PMID- 11513043
TI  - Two new roridins isolated from Myrothecium sp.

PMID- 11513044
TI  - Epicorazine C, an antimicrobial metabolite from Stereum hirsutum HKI 0195.

PMID- 11513045
TI  - Spirobenzofuran, a new bioactive metabolite from Acremonium sp.HKI 0230.

PMID- 11513046
TI  - The adaptive model of thermal comfort and energy conservation in the built
      environment.
AB  - Current thermal comfort standards and the models underpinning them purport to be
      equally applicable across all types of building, ventilation, occupancy pattern
      and climate zone. A recent research project sponsored by the American Society of
      Heating, Refrigerating and Air-Conditioning Engineers (ASHRAE, RP-884) critically
      evaluated these assumptions by statistically analysing a large database of
      research results in building comfort studies from all over the world (n=22,346).
      The results reported in this paper indicated a clear dependence of indoor comfort
      temperatures on outdoor air temperatures (instead of outdoor effective
      temperature ET* used in RP-884), especially in buildings that were free-running
      or naturally ventilated. These findings encourage significant revisions of
      ASHRAE's comfort standard in terms of climatically relevant prescriptions. The
      paper highlights the potential for reduced cooling energy requirements by
      designing for natural or hybrid ventilation in many moderate climate zones of the
      world.

PMID- 11513047
TI  - Application of a progressive-difference method to identify climatic factors
      causing variation in the rice yield in the Yangtze Delta, China.
AB  - Time series of rice yields consist of a technology-driven trend and variations
      caused by climate fluctuations. To explore the relationship between yields and
      climate, the trend and temporal variation often have to be separated. In this
      study, a progressive-difference method was applied to eliminate the trend in time
      series. By differentiating yields and climatic factors in 2 successive years, the
      relationship between variations in yield and climatic factors was determined with
      multiple-regression analysis. The number of hours of sunshine, the temperature
      and the precipitation were each defined for different intervals during the
      growing season and used as different regression variables. Rice yields and
      climate data for the Yangtze Delta of China from 1961 to 1990 were used as a case
      study. The number of hours of sunshine during the tillering stage and the heading
      to milk stage particularly affected the yield. In both periods radiation was low.
      In the first period, the vegetative organs of the rice crop were formed while in
      the second period solar radiation was important for grain filling. The average
      temperature during the tillering to jointing stage reached its maximum, which
      affected rice yields negatively. Precipitation was generally low during the
      jointing and booting stages, which had a positive correlation with yield, while
      high precipitation had a negative effect during the milk stage. The results
      indicate that the climatic factors should be expressed as 20- to 30-day averages
      in the Yangtze Delta; a shorter or longer period, e.g. 10 or 40 days, is less
      appropriate.

PMID- 11513048
TI  - Model for forecasting Olea europaea L. airborne pollen in South-West Andalusia,
      Spain.
AB  - Data on predicted average and maximum airborne pollen concentrations and the
      dates on which these maximum values are expected are of undoubted value to
      allergists and allergy sufferers, as well as to agronomists. This paper reports
      on the development of predictive models for calculating total annual pollen
      output, on the basis of pollen and weather data compiled over the last 19 years
      (1982-2000) for Cordoba (Spain). Models were tested in order to predict the 2000
      pollen season; in addition, and in view of the heavy rainfall recorded in spring
      2000, the 1982-1998 data set was used to test the model for 1999. The results of
      the multiple regression analysis show that the variables exerting the greatest
      influence on the pollen index were rainfall in March and temperatures over the
      months prior to the flowering period. For prediction of maximum values and dates
      on which these values might be expected, the start of the pollen season was used
      as an additional independent variable. Temperature proved the best variable for
      this prediction. Results improved when the 5-day moving average was taken into
      account. Testing of the predictive model for 1999 and 2000 yielded fairly similar
      results. In both cases, the difference between expected and observed pollen data
      was no greater than 10%. However, significant differences were recorded between
      forecast and expected maximum and minimum values, owing to the influence of
      rainfall during the flowering period.

PMID- 11513049
TI  - Correlation of spring spore concentrations and meteorological conditions in
      Tulsa, Oklahoma.
AB  - Different spore types are abundant in the atmosphere depending on the weather
      conditions. Ascospores generally follow precipitation, while spore types such as
      Alternaria and Cladosporium are abundant in dry conditions. This project
      attempted to correlate fungal spore concentrations with meteorological data from
      Tulsa, Oklahoma during May 1998 and May 1999. Air samples were collected and
      analyzed by the 12-traverse method. The spore types included were Cladosporium,
      Alternaria, Epicoccum, Curvularia, Pithomyces, Drechslera, smut spores,
      ascospores, basidiospores, and other spores. Weather variables included
      precipitation levels, temperature, dew point, air pressure, wind speed, wind
      direction and wind gusts. There were over 242.57 mm of rainfall in May 1999 and
      only 64.01 mm in May 1998. The most abundant spore types during May 1998 and May
      1999 were Cladosporium, ascospores, and basidiospores. Results showed that there
      were significant differences in the dry-air spora between May 1998 and May 1999.
      There were twice as many Cladosporium in May 1998 as in May 1999; both ascospores
      and basidiospores showed little change. Multiple regression analysis was used to
      determine which meteorological variables influenced spore concentrations. Results
      showed that there was no single model for all spore types. Different combinations
      of factors were predictors of concentration for the various fungi examined;
      however, temperature and dew point seemed to be the most important meteorological
      factors.

PMID- 11513050
TI  - Effects of wall linings on moisture ingress into traditional grain storage pits.
AB  - Increasing climate variability, resulting in frequent years of poor rainfall, has
      recently subjected the traditional subsistence farmers in the Central Clay Plain
      of the Sudan to longer periods of food shortage. However, excess production in
      years of good rainfall could bridge the gap of years with poor rainfall if the
      grain is properly stored. Resource-poor farmers have tried several linings to
      improve the traditional underground pit ("matmura") they use for storage of
      sorghum. In the experimental study described here, pits with two types of lining:
      (i) a mixture of mud, cow dung and straw and (ii) sorghum chaff, were compared
      with unlined pits. Six closed pits were used, two for each type, and temperature
      and moisture content were monitored. It was found that the temperature increased
      in all pits and at all positions within the pits, with few differences between
      the linings. Moisture levels also increased everywhere but the sources of
      moisture were at the sides and bottoms of the pits. The chaff-lined pits were
      superior to the others because they showed smaller increases in moisture content
      at all positions and thus maintained a better quality of sorghum. Joint
      traditional assessments with local farmers after the pits were opened supported
      these findings.

PMID- 11513051
TI  - An investigation of relationships between climate and dengue using a water
      budgeting technique.
AB  - Climatic water budget indicators were used to assess intra- and interannual
      variations in dengue incidence for San Juan, Puerto Rico. Multivariate stochastic
      relationships between dengue and the water budget were developed to (1) determine
      and quantify the particular climatic measures and their associated lag periods
      related to dengue variations, and (2) assess their use for dengue prediction and
      initiation of emergency response procedures. Such a predictive model would be
      advantageous because it is based on reliable, easily obtained, and low-cost
      weather observations. Daily running averages of water budget variables over an 8
      week period were related to daily running averages of unconfirmed dengue totals
      (1988-1993). Resultant models show that a variety of water budget and traditional
      climate measures over the full 8-week period are associated with dengue. The mean
      seasonal variation in dengue is highly related (R2=88.1%) to the mean seasonal
      climate variation, with those thermal and energy variables immediately preceding
      the dengue response showing the strongest relationships. However, moisture
      variables, predominantly in the form of surplus, are more influential many weeks
      in advance. For the interannual model (R2=44.1%), energy change, thermal change,
      and moisture variables are significant across the 8-week period, with moisture
      variables playing a stronger role than in the intraannual model. Standardisation
      substantially changes the importance and timing of the variables, and suggests
      that dengue during this period is more associated with the mean annual variation
      of climate than deviations from mean conditions. A dengue early-warning model
      (based on 5 weeks of climate data) was also developed to predict dengue incidence
      3 weeks later. While this predictive model is not reliable as a sole predictor of
      dengue in San Juan, it may be useful as part of a multifaceted watch/warning
      system.

PMID- 11513052
TI  - Natural environmental associations in a 50-day human electrocardiogram.
AB  - Meteorotropic associations of heart rate (HR) and HR variability (HRV) were
      investigated in a clinically healthy 48-year-old man in Kiev. His
      electrocardiogram (ECG) was determined over 50 days by fitting him with an
      ambulatorily wearable device; various natural physical environmental variables
      were also monitored. The mean inter-beat interval, the standard deviation of
      these intervals, the spectral power in several frequency ranges, the power ratio
      of the approx. 10.5-s/approx. 3.6-s spectral components and other aspects of HRV
      were computed over consecutive 14.4-min intervals. Together with ordinary
      meteorological variables, geomagnetic disturbances (GMD) and fluctuations of
      atmospheric pressure (FAP) in the range 0.01-0.10 Hz (10-100 s) were measured.
      The assessable infradian spectra (with frequencies lower than 1 cycle/28 hours)
      of all HRV parameters showed two major components with periods of about 3.5 and
      10 days. Two environmental variables, FAP and wind speed (with which FAP is
      closely related), revealed both of these rhythms and showed the greatest cross
      spectral coherence (0.70-0.98) with corresponding oscillations of HRV. Less
      specific but statistically significant product-moment correlations with major HRV
      indices were also found; most of these were with FAP, but correlations with air
      temperature, humidity, wind speed and geomagnetic disturbances were also found.
      Long-term ECG recording, essential in the detection of infradian rhythms, proved
      to be sensitive to physical environmental variables, notably meteorological ones.
      FAP, usually neglected since its role has not been considered in previous
      biometeorological studies, or some factor closely related to FAP is probably
      involved in synchronizing or influencing the approximately 3.5-day HR and HRV
      rhythms in humans.

PMID- 11513053
TI  - NSAIDS, COX-2 inhibitors and tramadol: acute postoperative pain management in day
      case surgery patients.

PMID- 11513054
TI  - Role of tramadol in reducing pain on propofol injection.
AB  - Propofol is frequently associated with pain on injection. We evaluated the effect
      of tramadol in a randomised, double-blind study using a tourniquet venous
      retention technique. Normal saline placebo was given intravenously to patients in
      Group 1 (n = 30),tramadol 50 mg to Group 2 (n = 30), and lignocaine 50 mg to
      Group 3 (n = 30). The venous retention of drugs was maintained for 1 minute,
      followed by tourniquet release and intravenous administration of propofol. Pain
      assessment was made immediately after propofol injection. There was a significant
      reduction in the incidence of pain associated with propofol administration in
      patients pretreated with lignocaine and tramadol (P < 0.05). In addition,
      pretreatment with tramadol was as effective as lignocaine in reducing pain on
      propofol injection.

PMID- 11513055
TI  - Fractures in transfusion dependent beta thalassemia--an Indian study.
AB  - AIM OF STUDY: To analyse the incidence of fractures in beta thalassemia patients
      and to identify causative factors. METHODS: We examined all cases of transfusion
      dependent beta thalassemia (TDBT) seen at our institute over a two-year period.
      The transfusion records, incidence of fractures, cause of fracture and Hb levels
      were recorded. Radiographs of the involved parts were taken in cases with
      fractures only. RESULTS AND CONCLUSIONS: Amongst 105 cases of TDBT assessed, 14
      sustained a total of 28 fractures. Seven patients sustained more than one
      fracture. Two thirds of these fractures were caused by trivial trauma. All
      fractures, except one, were of the closed type. Radiologically, fractures
      frequently showed minimal or no displacement. All fractures were successfully
      treated by closed modalities of treatment. Majority of the fractures healed
      within normal union time for a given bone. Permanent deformities and gross limb
      length discrepancies were uncommon. On reviewing the literature, we noted that
      the incidence of fractures in our series and in the latest reports was lesser
      than previously reported. We postulate that this is a result of better and
      earlier control of hemoglobin status by improved transfusion techniques, and
      earlier recognition of the disease. Difficulties arise due to inadequate blood
      transfusion facilities in developing countries.

PMID- 11513056
TI  - Heparin induced thrombocytopenia.
AB  - BACKGROUND: Heparin is a widely used antithrombotic agent for treatment of
      ischemic cerebrovascular disease. One of its most important side-effects is
      thrombocytopenia which may lead to potentially life-threatening haemorrhagic and
      thrombotic complications. METHODS: We performed a prospective study to determine
      the frequency of heparin induced thrombocytopenia. Heparin induced
      thrombocytopenia is defined as a platelet count of less than 150 x 10(3)/mm3 or a
      decrease in platelet count to 30% to 50% from baseline. Daily platelet counts
      were obtained in 50 adult patients who were treated with the same lot of
      intravenous bovine heparin. Two patients (4%) developed thrombocytopenia with
      onset varying from four to seven days after heparin was started. In both cases,
      platelet counts returned to baseline levels three to five days after cessation of
      therapy. No ischemic or haemorrhagic complications occurred. CONCLUSION: Heparin
      induced thrombocytopenia is a common complication of intravenous heparin
      treatment. Clinicians treating patients with heparin should determine platelet
      counts at baseline and henceforth at regular intervals beginning from the fifth
      day of therapy. We recommend commencement of warfarin therapy concurrently with
      heparin infusion and discontinuation of heparin once warfarin has become
      effective. All doctors must be vigilant to this reversible common complication.

PMID- 11513057
TI  - A clinical review of granulosa cell tumours of the ovary cases in KKH.
AB  - INTRODUCTION: Granulosa cell tumour (GCT) represents the largest group of sex
      cord stromal tumours and comprises 1.5-3% of ovarian malignancy. The aim is to
      determine the incidence of the disease, study the profile of local patients, and
      assess the use of imaging studies in the diagnosis of the tumour. MATERIAL AND
      METHODS: Clinical records of 19 patients diagnosed with GCT between October 1988
      and July 1997 in Kandang Kerbau Hospital (KKH) were reviewed. RESULTS: GCT
      accounts for 3.5% of ovarian malignancy (54 out of 1552) in Singapore, of which
      94.7% are adult GCT. In our study, patients are mainly peri/postmenopausal women
      (63.2%) in their 50s who experience post-menopausal bleeding. There is a high
      incidence of association with endometrial hyperplasia (40%). Ultrasound scans are
      able to predict the size and involvement of the tumour rather accurately. In our
      study sample, 13 patients (68.4%) presented with Stage 1 of the disease, none
      with Stage 2, 1 with Stage 3 (5.3%) and none with Stage 4. The other 5 patients
      (26.3%) were unstaged. Only one patient required adjuvant chemotherapy.
      CONCLUSION: The local data with regards to GCT is congruent with those found in
      foreign literature. However, in our study, there were no patients with recurrence
      whereas GCTs are known to be late recurring in up to 20% of patients 10-20 years
      after diagnosis. This is probably attributed to the relatively short period of
      follow-up in this study. Thus, despite the fact that there is no evidence of
      recurrence of disease in our current study, we still recommend a vigilant follow
      up protocol on all patients as literature has proven that with early detection of
      recurrences, it is possible to achieve complete cure.

PMID- 11513058
TI  - Social and health profiles of rural elderly Malays.
AB  - AIM: To evaluate the social and health functions of rural elderly Malays. METHOD:
      A survey was carried out on 350 elderly Malays aged 60 and above using a set of
      socio and health questionnaires. RESULTS: The majority of elderly people in the
      study were married (64%), unemployed with no pension (76%), relied on children
      for their main economic resources (62%) and perceived that they have sufficient
      money to buy the food they require (61%). Most of the subjects felt healthy,
      contented and satisfied with their everyday life, were able to do most of the
      Activities of Daily Living (ADL) tasks and were actively involved in community
      activities. However, most of the subjects (60%) had either one or two diagnosed
      chronic diseases. Thus, only 15% of the subjects had not taken any type of
      medicines during the previous 12 months. CONCLUSION: Although the majority of the
      elderly in this study were able to perform all the ADL tasks and perceived their
      health as good, physical impairments (eg. sight, hearing and chewing
      difficulties) are prevalent and the use of medicines is widespread. It is
      expected that in future a greater proportion of rural elderly Malays will live
      alone and will face economic and health problems because of the lack of
      sufficient and satisfactory programmes for this age group.

PMID- 11513059
TI  - Fatal chemotherapy associated Clostridium difficile infection--a case report.
AB  - Clostridium difficile associated diarrhoea or Pseudomembranous colitis
      occasionally occurs without prior antibiotic usage. While the association of
      chemotherapy and Clostridium difficile infection has previously been well
      recorded, the true incidence is unknown. We report a case of Clostridium
      difficile associated diarrhoea after chemotherapy for lung cancer. The fatal
      outcome in this case and the increasing use of chemotherapy in this country
      highlights the need to have a high index of suspicion in any case of unexplained
      diarrhoea post chemotherapy. A review of the literature is presented.

PMID- 11513060
TI  - A case of pathological gambling--its features and mangement.
AB  - Pathological gambling (PG) represents the end spectrum of gambling behaviours. It
      is characterised by constantly recurring gambling behaviour which is maladaptive.
      This case illustrates how an Asian woman pathological gambler progresses through
      the different stages of development of the gambling habit, and how a multi-modal
      treatment approach has helped her regain psychosocial function. In addition, the
      maintenance factors, typical and atypical associated features, and difficulties
      in the management of such a case are highlighted.

PMID- 11513061
TI  - Management of haemorrhagic stroke with hyperbaric oxygen therapy--a case report.
AB  - Hyperbaric oxygen therapy (HBOT) has been used in the treatment of cerebral
      ischaemia with positive effects on tissue oxygenation. We present a case of
      haemorrhagic stroke treated successfully with HBOT and review the literature on
      its role in cerebrovascular disease.

PMID- 11513062
TI  - Sezary syndrome in a Malay--case report and literature review.
AB  - Sezary syndrome is a rare form of primary cutaneous T cell lymphoma. It is a
      distinct systemic variant of mycosis fungoides, marked by erythroderma,
      lymphadenopathy and circulating cerebriform lymphocytes in the peripheral blood.
      We report a case of Sezary syndrome in a 61-year-old Malay man with a five-year
      history of indurated plaques, ulcers and tumours on the head and trunk, with
      characteristic findings on physical examination, skin biopsy, electron
      microscopy, immunophenotyping and peripheral blood film. A literature review on
      Sezary syndrome is presented.

PMID- 11513063
TI  - Laparoscopic treatment of a twisted hyperstimulated ovary after IVF.
AB  - Ovarian Hyperstimulation Syndrome (OHSS) is a common problem associated with
      modern In-Vitro Fertilisation techniques (IVF). However, torsion of a
      hyperstimulated ovary occurring after IVF is a much rarer event. In this case
      report, we will describe the laparoscopic management of a pregnant patient with a
      twisted hyperstimulated ovary after an IVF programme.

PMID- 11513064
TI  - Article: In the absence of dietary surveillance, chitosan does not reduce plasma
      lipids...(SC Ho, et al)(SMJ Vol 42 Issue 1 January 2001.

PMID- 11513065
TI  - Clinics in diagnostic imaging (61). Left primary megaureter with lower ureteric
      stone.
AB  - Megaureter is infrequently diagnosed in adulthood. A 27-year-old man who
      presented with recurrent left loin pain was found to have megaureter on
      intravenous urography. His symptoms did not resolve after balloon dilatation of
      the 3 cm stenotic aperistaltic segment of the lower ureter. He eventually
      underwent ureteric re-implantation with satisfactory symptomatic relief. The
      resolution of obstruction was demonstrated radiologically. The role of imaging in
      the diagnosis and surveillance of megaureter, as well as indications for
      intervention, are discussed.

PMID- 11513066
TI  - Indoor air pollution and respiratory health in urban and rural China.
AB  - During the summer of 1999, information about respiratory health outcomes and
      relevant covariates was collected from 3,709 Chinese adults in Beijing, Anqing
      City, and rural communities in Anqing Prefecture. Indoor PM10 and SO2 were
      measured in a random sample of selected households. Using logistic regression and
      controlling for important covariates (excluding PM10 and SO2) and familial
      intraclass correlation, highly significant differences were found between study
      areas in the prevalences of chronic cough, chronic phlegm, wheeze, and shortness
      of breath, but not physician-diagnosed asthma. Generally, the lowest prevalence
      of respiratory symptoms was observed in Anqing City, a higher prevalence in rural
      Anqing, and the highest prevalence in Beijing. Median indoor concentrations of
      PM10 were similar in Anqing City (239 microg/m3) and rural Anqing (248
      microg/m3), but much higher in Beijing (557 microg/m3). Median indoor
      concentrations of SO2 were similar in all three areas (Beijing: 14 microg/m3,
      Anqing City: 25 microg/m3, rural Anqing: 20 microg/m3).

PMID- 11513067
TI  - Solvent exposures at shoe factories and workshops in Hebron City, West Bank.
AB  - Exposure to organic solvents has been reported to increase the risks for acute
      and chronic health effects among shoe industry workers. In developing countries,
      protection against chemical exposures is often not provided. The study was
      conducted to identify working conditions and estimate the concentrations of
      organic solvents used in shoe factories and workshops in Hebron City. Personal
      interviews containing questions related to personal protective equipment (PPE)
      were used to identify working conditions, and samples collected from factories
      and workshops were analyzed using gas chromatography. Geometric means (GMs) were
      calculated for the solvents. Six major organic solvents were detected in the
      factories. Acetone (GM = 51.5 mg/m3, GSD = 3.82) was common in gluing tasks.
      Dichloromethane (GM = 47 mg/m3, GSD = 2.62) was common in cleaning tasks.
      Heptane, methylethyl ketone, n-hexane, and toluene were common in gluing tasks.
      Four major organic solvents were detected in the workshops: acetone (GM = 32.3
      mg/m:3, GSD = 6.33), toluene (GM = 70.3 mg/m3, GSD = 3.06), n-hexane (GM = 19.4
      mg/m3:, GSD = 2.65), and methylethyl ketone (GM = 130 mg/mM3, GSD = 1.5). 81% of
      the factory workers had never used respiratory protective equipment, and 92% had
      never used work clothes. 97% of the workers in the workshops had never used
      respiratory protective equipment, 94% had never worn gloves, and 90% had never
      used work clothes. Exposures to solvents in the absence of personal Protective
      equipment, tasks barriers, and mechanical ventilation can adversely affect
      health.

PMID- 11513068
TI  - Assessment of pentachlorophenol-exposed timber workers using a test-of-poisoning
      model.
AB  - Sixty-two former New Zealand timber workers who were exposed to pentachlorophenol
      (PCP) at work were interviewed, examined, and assessed both by laboratory
      investigations and psychometrically for clinical syndromes that could be related
      to PCP exposure. Three such syndromes were identified: an acute complex of fever,
      headaches, upper and lower respiratory tract and eye irritation, skin disease,
      and foul smelling and discolored sweat; a chronic fatigue syndrome, beginning
      while still at work and frequently persisting; and a delayed encephalopathy.
      Neither of the sustained syndromes was considered characteristic of PCP
      poisoning, and many confounders were identified. An exposure index and a test-of
      poisoning score had a statistically insignificant correlation.

PMID- 11513070
TI  - The distribution of occupations in two populations with upper limb pain.
AB  - Occupations of two geographically distinct populations of patients with upper
      limb pain were examined. Relative risks for being in an occupation were
      calculated for subjects with epicondylitis, carpal tunnel syndrome, and pain
      syndromes in one population and nonspecific occupational overuse syndrome (OOS)
      in the other. Population A subjects (806 female, 154 male Auckland clinic
      referrals) with epicondylitis and carpal tunnel syndrome had higher rates of
      manual occupations compared with the Auckland employed population, consistent
      with previous research. Both Population A and Population B subjects (1,188
      female, 499 male national notifications to the Department of Labour) with pain
      syndrome or nonspecific OOS had increased rates of clerical occupations. Relative
      risks ranged from 2.24 (95% CI 1.69,2.97) to 3.92 (3.50 ,4.40). Word processor
      operators, data-entry operators, and mail sorters were overrepresented in both
      populations. An unexplained association between nonspecific upper arm pain and
      being in some clerical occupations requires further research.

PMID- 11513069
TI  - An occupational risk survey of a refractory brick company in Ha Noi, Viet Nam.
AB  - Viet Nam has an increasing need for building materials, including refractory
      bricks. Little is known regarding the occupational hazards incurred in brick
      manufacturing. To determine the occupational health hazards posed by a refractory
      brick operation in Ha Noi, Viet Nam, a cross-sectional occupational risk survey
      was conducted, focusing on respirable dust hazards. It included an industrial
      hygiene walk-through and gravimetric dust analysis. Noise, heat, lack of head
      protection, and dust exposure were hazards identified at the brick-manufacturing
      site. Respiratory protection involved a three-layer cloth mask that had not been
      tested for efficacy. Silica dust exposure levels exceeded the Vietnamese
      permissible exposure level by almost fivefold based on gravimetric assessment and
      estimated silica content. This brick manufacturing site contains significant
      injury and respiratory illness hazards. Further investigations are necessary to
      begin to develop occupational safety measures at the site.

PMID- 11513071
TI  - Employee exposure to chromium and plasma lipid oxidation.
AB  - Exposure to chromium increases free-radical species in the body, which has an
      adverse biologic effect. In view of evidence that the oxidation of low-density
      lipoproteins is important in the pathogenesis of atherosclerosis, the authors
      measured plasma lipid oxidation and antioxidant levels in 11 welders chronically
      exposed to chromium and compared them with levels in 15 matched controls.
      Exposure level was determined by urinalysis. Plasma lipid peroxidation and
      susceptibility to oxidation were determined by measuring generated thiobarbituric
      acid reactive substance (TBARS) and lipid peroxides. Total plasma antioxidant
      status and serum paraoxonase activity were also measured. The Kruskal-Wallis test
      was used to test for statistical significance. There was no significant
      difference between the groups with regard to lipid peroxidation, plasma lipid
      susceptibility to oxidation, total plasma antioxidant status, or serum
      paraoxonase. Three workers with urinary chromium levels over the biologic
      exposure index limit (> 10.0 microg/g creatinine) had higher plasma lipid
      peroxidation and lipid susceptibility to oxidation compared with the rest of the
      study group. The results suggest that welders exposed to chromium have increased
      plasma lipid oxidation. The small numbers of subjects and those with elevated
      urinary chromium limit the power of this preliminary study. Further studies of
      the association of chromium with plasma lipid oxidation are warranted.

PMID- 11513072
TI  - Childhood lead exposure in Oporto, Portugal.
AB  - The study aims were to evaluate childhood lead poisoning in Oporto, Portugal,
      characterize childhood exposures, find solutions to reduce them, and call the
      community's attention to the need for preventive measures. Children aged 1-5
      years living in Oporto Historical Center, were the target population. Data were
      gathered by means of a questionnaire and blood lead analyses for 240 children who
      attended four randomly selected kindergartens. The geometric mean blood lead
      concentration was 13.9 microg/dl and lead poisoning prevalence (blood lead levels
      > 10 microg/dL) was 85.8%. Important sources of lead poisoning were father's
      occupation, mother's smoking habits, and poor hygiene and pica associated with
      contaminated soils and lead paint. Families were unaware of the problem of lead
      exposure and its harmful effects. The data indicate that high levels of childhood
      lead exposures still prevail in Oporto City, an important public health finding
      that deserves authorities' attention.

PMID- 11513073
TI  - Musculoskeletal disorders in industrial workers of Delhi.
AB  - To study the musculoskeletal disorders in industrial workers in Delhi, 631
      workers from 60 factories representing small and medium-sized enterprises located
      in Delhi were interviewed. Many (59.4%) of the workers had musculoskeletal
      disorders. Tailors, those working near furnaces, cooks, workers in buffing,
      checking and assembly work, and those working with chemicals had the most joint
      complaints. Cervical pain was more frequent in tailoring and packing work,
      whereas lumbar pain was more common in buffing, operators working on presses,
      those using hand and power tools, and those lifting heavy manual loads. Contract
      workers had less musculoskeletal morbidity than regular and temporary workers.
      Skilled workers also had less morbidity. Workers experiencing more job
      satisfaction reported fewer musculoskeletal disorders. The high prevalence of
      musculoskeletal disorders in workers needs urgent attention from the health and
      labor sectors. An ergonomic approach to prevention should be considered. The
      current manual load handling limits prescribed in the Indian Factory Rules
      potentially expose workers to back stress. It is also inappropriate to have
      separate load-lifting limits for men and women. Research is urgently required to
      determine the safe load handling limits for the Indian working population based
      on ergonomic principles. Until internationally acceptable safe limits are
      established, back pain should be a notifiable disease in India.

PMID- 11513074
TI  - Integrated job analysis: a technique to document job activities and to identify
      occupational risk factors and modes of remediation and accommodation.
AB  - Integrated job analysis is a form of job evaluation that considers cognitive,
      physical, and environmental factors related to occupational performance,
      assessment, and rehabilitation. First, the analysis describes cognitive factors
      that determine worker interactions with data, people, and things and educational
      and training requirements. A task description is provided and tools used are
      identified, along with job physical requirements, environmental conditions, and
      personal protective equipment needs. Supplementary information is elicited to
      describe the environment, task requirements, workstations, and work areas. Based
      on this information, preliminary recommendations are made for abating
      occupational hazards, and accommodations for alternatively-challenged individuals
      are identified. The value of this approach is in the detailed documentation of
      all occupational components regarding a specific job classification, which can
      then guide the development of meaningful preplacement and periodic medical
      examinations, physical agility tests, training criteria, rehabilitation, and
      return-to-work regimens.

PMID- 11513075
TI  - International Code of Conduct (ethics) for occupational health and safety
      professionals.

PMID- 11513076
TI  - Occupational health in Central and Eastern Europe in the 1990s: resources and
      suggested research agenda.

PMID- 11513077
TI  - WTO upholds French ban on chrysotile.

PMID- 11513078
TI  - Establishment of human embryonic brain cell lines.

PMID- 11513079
TI  - Density differential responses of embryonic fibroblasts.

PMID- 11513080
TI  - Establishment of a human hepatocyte line (OUMS-29) having CYP 1A1 and 1A2
      activities from fetal liver tissue by transfection of SV40 LT.
AB  - Immortalized human hepatocytes that can retain functions of drug-metabolizing
      enzymes would be useful for medical and pharmacological studies and for
      constructing an artificial liver. The aim of this study was to establish
      immortalized human hepatocyte lines having differentiated liver-specific
      functions. pSVneo deoxyribonucleic acid, which contains large and small T genes
      in the early region of simian virus 40, was introduced into hepatocytes that had
      been obtained from the liver of a 21-wk-old fetus. Neomycin-resistant
      immortalized colonies were cloned and expanded to mass cultures to examine
      hepatic functions. Cells were cultured in a chemically defined serum-free medium,
      ASF104, which contains no peptides other than recombinant human transferrin and
      insulin. As a result, an immortal human hepatocyte cell line (OUMS-29) having
      liver-specific functions was established from one of the 13 clones. Expression of
      CYP 1A1 and 1A2 messenger ribonucleic acid by the cells was induced by treatment
      with benz[a]pyrene, 3-methylcholanthrene, and benz[a]anthracene. OUMS-29 cells
      had both the polycyclic aromatic hydrocarbon receptor (AhR) and AhR nuclear
      translocator. Consequently 7-ethoxyresorufin deethylase activity of the cells was
      induced time- and dose-dependently by these polycyclic aromatic hydrocarbons.
      This cell line is expected to be instrumental as an alternative method in animal
      experiments for studying hepatocarcinogenesis, drug metabolisms of liver cells,
      and hepatic toxicology.

PMID- 11513081
TI  - Mechanical fluid flow and surfactant-TA influence activation of macrophages.
AB  - We examined the effect of mechanical fluid flow and surfactant on macrophage
      aggregation as the indication of macrophage activation. Mechanical fluid flow
      enhanced aggregation in phorbol myristate acetate (PMA)-treated human myeloid
      leukemic cell lines (HL-60 cells), but had no effect on differentiation of PMA
      treated HL-60 cells. Surfactant-TA (an artificial surfactant) inhibited fluid
      flow-induced aggregation, but had no effect on differentiation of PMA-treated HL
      60 cells. Human alveolar macrophages spontaneously formed small aggregates
      without stimulation. This aggregation was enhanced by fluid flow and inhibited by
      surfactant-TA. Taken together, these data suggest that macrophage activation is
      affected by fluid flow and surfactants.

PMID- 11513082
TI  - Inhibition of environmental estrogen-induced proliferation of human breast
      carcinoma MCF-7 cells by flavonoids.
AB  - In the present study, we evaluated the individual and combined effects of
      environmental estrogens and flavonoids on the proliferation of human breast
      carcinoma MCF-7 cells. These compounds are as follows: (1) pharmaceutical
      chemicals such as diethylstilbestrol, 17alpha-ethynylestradiol (17ES), tamoxifen,
      mestranol, and clomiphene, (2) industrial chemicals such as bisphenol A (BisA), 4
      octylphenol (OP), 4-nonylphenol (NP), and p,p'-biphenol, and (3) flavonoids such
      as daidzein (D), genistein (G), quercetin (Q), and luteolin (L). We found that
      nanomolar concentrations of 17ES, BisA, OP, and NP were sufficient to stimulate
      the proliferation of MCF-7 cells. Among them, 1 microM BisA exhibited cell
      proliferation-stimulating activity as strong as 10 nM 17beta-estradiol; and D and
      G exhibited cell proliferation-stimulating activity at 10 nM. On the other hand,
      Q and L exhibited cell proliferation-inhibiting activity. We also found that 10
      nM flavonoids, such as D, G, Q, and L, were able to inhibit the proliferation
      stimulating activity in MCF-7 cells by 1 microM environmental estrogens.

PMID- 11513083
TI  - Ultrastructural observations on effects of different concentrations of calcium
      and thyroxine in vitro on larval epidermal cells of Rana catesbeiana tadpoles.
AB  - During anuran metamorphosis dramatic changes in morphogenesis and differentiation
      of epidermis occur under the influence of thyroid hormones. Modification of ionic
      calcium concentration also markedly alters the pattern of proliferation and
      differentiation in amphibian epidermal cells in vitro. The present study was
      designed to determine the direct effect of low (0.05 mM) and high (0.5 mM)
      calcium (Ca2+) in the absence or presence of thyroxine (10(-7) M) on epidermal
      cells of the body and tail tissue in vitro. When tail fin and body skin explants
      were maintained in low (0.05 mM) calcium for 48 h, normal ultrastructural
      morphology and integrity of the cells was observed in both the tissue types. When
      tissues were exposed to high levels of calcium (0.5 mM) in culture medium, tail
      epidermis showed stratification, and skein cells exhibited apoptosis, both in the
      presence or absence of thyroid hormones. Under high calcium conditions, the body
      epidermis showed keratinization of apical cells, apoptosis of skein cells, and
      increased desmosome formation. These results suggest that (1) optimal Ca2+
      concentration for larval epidermal cells is quite low (0.05 mM), (2) high Ca2+
      leads to keratinization only in body epidermis, and (3) apoptosis occurred in
      skein cells of both the tissues at high Ca2+ concentrations (0.5 mM). The present
      study therefore suggests that the extracellular calcium concentration regulates
      the process of cell death and differentiation in Rana catesbeiana larval
      epidermis, and this effect may be similar to the effect of calcium on mammalian
      epidermal cells.

PMID- 11513084
TI  - Stable cell lines expressing baculovirus P35: resistance to apoptosis and
      nutrient stress, and increased glycoprotein secretion.
AB  - The baculovirus P35 protein is a caspase inhibitor that prevents the induction of
      apoptosis during infection of Sf21 cells by Autographa californica multicapsid
      nucleopolyhedrovirus (AcMNPV). P35 inhibits the induction of apoptosis in a broad
      range of cells and circumstances. In this study, we examined the effects of
      constitutive cellular P35 expression on the response of cells to stressful
      culture conditions and on protein production in AcMNPV infected cells. Sf9 cell
      lines expressing AcMNPV P35 or an epitope-tagged P35 protein were generated using
      a double selection technique, involving selection in the antibiotic G418,
      followed by a second round of selection by exposure to actinomycin D, a potent
      inducer of apoptosis in Sf9 cells. Clonal cell lines were generated and examined
      for (1) resistance to actinomycin D induced apoptosis, (2) resistance to nutrient
      deprivation, and (3) baculovirus expression of intracellular and secreted
      proteins. When compared with Sf9 cells, two P35-expressing cell lines (Sf9P35AcV5
      1 and Sf9P35AcV5-3) showed increased resistance to actinomycin D-induced
      apoptosis and a profound resistance to nutrient deprivation. When these cell
      lines were infected with a recombinant baculovirus expressing a secreted
      glycoprotein (secreted alkaline phosphatase), expression of the glycoprotein from
      these cells exceeded that from the parental Sf9 cells and was comparable to
      expression levels obtained from Tn5B1-4 cells, the best available cell line for
      high-level expression. Increased levels of protein secretion in Sf9P35AcV5-1 and
      Sf9P35AcV5-3 cells appear to result from a prolonged infection cycle and
      accumulation of the secreted glycoprotein.

PMID- 11513085
TI  - Tumor necrosis factor-alpha binding in porcine primary stromal-vascular cell
      cultures.
AB  - The binding characteristics of tumor necrosis factor-alpha receptors (TNFRs) in
      primary stromal-vascular cultures from fat tissue of 7-d-old pigs were analyzed.
      Cells were plated and maintained in 10% fetal bovine serum from day 0 to day 3
      and then switched to serum-free medium from day 3 to day 6 to induce lipid
      filling. On days 3 and 6 of culture, some of the cells were lysed for ligand and
      immunoblotting and the remainder subjected to competitive and inhibitory-binding
      assays. Media from day 6 of culture were subjected to ligand and immunoblotting.
      Competitive binding analysis showed one-site bindings, with IC50s in the
      nanomolar and Kds in the picomolar ranges, that were not significantly different
      at both time-points of measurement. However, the Bmax decreased significantly
      with differentiation. Preincubation with antibody against TNF receptor type 1
      (TNFR1) or TNF receptor type 2 reduced the specific binding by 95 and 15%,
      respectively, suggesting a dominating role of TNFR1 in 125I-labeled TNFalpha
      (125I-TNFalpha) binding. This was further supported by ligand blotting of cell
      lysates. Ligand and immunoblotting of cell lysates indicated that TNFalpha
      utilizes both types of surface receptors and their isoforms which were not
      modified during differentiation. Ligand blotting of media revealed soluble
      receptors with high Mr implying the formation of multimers. Immunoblotting
      suggested the presence of both types of TNFRs, but a greater abundance of soluble
      TNFR1. Also, it indicated the additional formation of smaller oligomers from both
      types of soluble receptors suggesting higher affinity of larger multimers for
      125I-TNFalpha.

PMID- 11513086
TI  - A milk growth factor extract reduces chemotherapeutic drug toxicity in epithelial
      cells in vitro.
AB  - Transforming growth factor-beta (TGF-beta) and insulin-like growth factor (IGF-I)
      can attenuate drug-induced cell death in epithelial cells. Since milk whey
      contains a mixture of these and other growth factors, we evaluated mitogenic
      bovine whey extract (MBWE) for protective activity against chemotherapy drug
      damage in cultured epithelial cells (mink lung, MvlLu). Etoposide and vinblastine
      reduced cell survival by up to 90%. This was attenuated by the addition of MBWE
      before and during drug exposure, but not following drug removal. MBWE was
      compared with individual growth factors known to be present in the mixture. IGF-I
      and platelet-derived growth factor were ineffective, whereas TGF-beta2 induced
      growth inhibition and cell survival, with a maximum response at 3 ng/ml. TGF
      beta2 bioactivity was also demonstrated by showing that acidification of MBWE (A
      MBWE), to activate TGF-beta2, enhanced its growth inhibitory and chemoprotective
      activities 60- and 12-fold, respectively. However, MBWE contained additional
      protective factors. When TGF-beta2 and the MBWE preparations were compared, on
      the basis of growth inhibition equivalents, MBWE protected cells against drug
      toxicity at concentrations an order of magnitude lower than with TGF-beta2 or A
      MBWE. Immunoneutralization of the TGF-beta present in MBWE and A-MBWE eliminated
      all growth inhibitory activity but not all cell survival activity. We conclude
      that the MBWE preparations are cytoprotective against two chemotherapy drugs when
      added before and during drug exposure. TGF-beta contributes to this activity, but
      the extracts contain other factors that promote the survival of epithelial cells
      after chemotherapy drug exposure.

PMID- 11513087
TI  - Preparation of monospecific polyclonal antibodies against Sambucus nigra lectin
      related protein, a glycosylated plant protein.
AB  - A simple, but highly efficient, method was developed for the purification of
      monospecific antibodies against the plant glycoprotein Sambucus nigra lectin
      related protein. In a first step, the antiserum is purified by affinity
      chromatography on a column with the immobilized antigen. To deplete the affinity
      purified antiserum from aspecific cross-reacting antibodies directed against the
      glycan part of the glycoprotein, a second affinity chromatography on an unrelated
      plant glycoprotein, in casu the Robinia pseudoacacia agglutinin, is included.

PMID- 11513088
TI  - Role of medium- and long-range interactions to the stability of the mutants of T4
      lysozyme.
AB  - Inter-residue interactions play an important role to the folding and stability of
      protein molecules. In this work, we analyze the role of medium- and long-range
      interactions to the stability of T4 lysozyme mutants. We found that, in buried
      mutations, the increase in long-range contacts upon mutations destabilizes the
      protein, whereas, in surface mutations, the increase in long-range contacts
      increases the stability, indicating the importance of surrounding polar residues
      to the stability of surface mutations. Further, the increase in medium-range
      contacts decreases the stability of buried and surface mutations and a direct
      relationship is observed between the increase of medium-range contacts and
      increase in stability for partially buried/exposed mutations. Moreover, the
      relationship between amino acid properties and stability of T4 lysozyme mutants
      at positions Ile3, Phe53, and Leu99 showed that the effect of medium- and long
      range contacts is less for buried mutations and the inter-residue contacts have
      significant correlation with the stability of partially buried mutations.

PMID- 11513089
TI  - Affinity enrichment of bovine lactoferrin in whey.
AB  - Bovine lactoferrin was enriched in various whey samples by affinity
      chromatography using immobilized gangliosides. Bovine gangliosides were isolated
      from fresh buttermilk using a combination of ultrafiltration and organic
      extraction. Isolated gangliosides were covalently immobilized onto controlled
      pore glass beads. The immobilized matrix contained 66 micrograms of gangliosides
      per gram of beads. After loading the matrix with reconstituted whey protein
      isolate (WPI) or whey protein concentrate (WPC), the matrix was washed with
      sodium phosphate buffer (pH 7) followed by sodium acetate buffer (pH 4) before
      elution of lactoferrin with 1 M NaCl in sodium acetate buffer. From the
      intensities of the protein bands in SDS-PAGE, lactoferrin constituted a minimum
      of 40% of the total protein in the salt eluted sample. WPI, pretrated by heating
      and ultrafiltration, showed the highest lactoferrin purity among protein sources,
      while WPI (10% wt/vol) showed the highest recovery. These results show that
      immobilized gangliosides can be used to enrich the lactoferrin content of whey.

PMID- 11513090
TI  - Perfusion chromatography separation of the tomato fruit-specific pectin
      methylesterase from a semipurified commercial enzyme preparation.
AB  - A rapid and simple method was developed, using perfusion chromatography media, to
      separate the fruit-specific pectin methylesterase (PME) isoform from the
      depolymerizing enzyme polygalacturonase (PG) and other contaminating pectinases
      present in a commercial tomato enzyme preparation. Pectinase activities were
      adsorbed onto a Poros HS (a strong cation exchanger) column in 20 M HEPES buffer
      at pH 7.5. The fruit-specific PME was eluted from the column with 80 mM NaCl,
      followed by a step to 300 mM NaCl to elute PG activity. Rechromatography of the
      PME activity peak with a linear gradient further resolved two PME isoenzymes and
      removed residual traces of PG activity. The PG activity peak was further treated
      with lectin affinity chromatography to provide purified PG enzyme, which was
      separated from a salt-dependent PME (tentatively identified as a "ubiquitous
      type" isoform), and a pectin acetylesterase. The later enzyme has not been
      reported previously in tomato. This method provides monocomponent enzymes that
      will be useful for studying enzyme mechanisms and for modifying pectin structure
      and functional properties.

PMID- 11513091
TI  - Purification of non-toxic, biodegradable arginine-based gemini surfactants,
      bis(Args), by ion exchange chromatography.
AB  - This paper presents an environmentally improved procedure for the preparative
      purification of a series of arginine-based gemini surfactants. The technique used
      was cation-exchange chromatography. Mixtures of boric-borate buffer, co-solvent
      (ethanol), and sodium chloride were tested as eluents. The influence of the
      buffer pH and the amount of co-solvent on the chromatographic process was studied
      for the model compound bis(Nalpha-lauroyl-L-arginine) 1,3-propanediamide
      dihydrochloride, C3(LA)2, and purification conditions were established. The
      method was scaled-up to the multigram level for C3(LA)2 and the rest of the
      series. The proposed preparative procedure involves simple equipment, low cost
      materials, and minimal amounts of solvent (water/ethanol), with low toxicity.

PMID- 11513092
TI  - Cleavage and purification of intein fusion proteins using the Streptococcus
      gordonii spex system.
AB  - A gram-positive bacterial expression vector using Streptococcus gordonii has been
      developed for expression and secretion, or surface anchoring of heterologous
      proteins. This system, termed Surface Protein Expression system or SPEX, has been
      used to express a variety of surface anchored and secreted proteins. In this
      study, the Mycobacterium xenopi (Mxe) GyrA intein and chitin binding domain from
      Bacillus circulans chitinase Al were used in conjunction with SPEX to express a
      fusion protein to facilitate secretion, cleavage, and purification. Streptococcus
      gordonii was transformed to express a secreted fusion protein consisting of a
      target protein with a C-terminal intein and chitin-binding domain. Two target
      proteins, the C-repeat region of the Streptococcus pyogenes M6 protein (M6) and
      the nuclease A (NucA) enzyme of Staphylococcus aureus, were expressed and tested
      for intein cleavage. The secreted fusion proteins were purified from culture
      medium by binding to chitin beads and subjected to reaction conditions to induce
      intein self-cleavage to release the target protein. The M6 and NucA fusion
      proteins were shown to bind chitin beads and elute under cleavage reaction
      conditions. In addition, NucA demonstrated enzyme activity both before and after
      intein cleavage.

PMID- 11513094
TI  - Purification and partial characterization of glyoxalase I from bovine brain.
AB  - Glyoxalase I was purified to homogeneity from bovine brain using affinity
      chromatography on S-hexylglutathione-Sepharose 6B with a yield of 22%. The enzyme
      was a dimer (44,000 Daltons) composed of, apparently, identical subunits (22,000
      Daltons), as shown by SDS electrophoresis, and contained one mole of
      Zn2+/monomer. The active site metal ion, Zn2+, was removed by dialysis against
      EDTA, but the activity of the apoenzyme obtained was not completely restored
      after addition of Co2+ and Zn2+ (<25%), while a recovery of 50% was obtained
      after addition of Mg2+. The enzyme was inhibited by S-bromobenzylglutathione and
      S-p-nitrobenzylglutathione with a Ki value of 21 microM and 32 microM,
      respectively. The highest dissociation constant observed for the brain enzyme
      with respect to that reported for human erythrocytes, or other mammalian forms of
      enzyme could be related to a tissue-specific dependence of the glyoxalase I
      activity.

PMID- 11513093
TI  - The activities of carbonic anhydrase and alkaline phosphatase in ancient human
      bones. Purification and characterization of outer peripheral, cytosolic, inner
      peripheral, and integral CA.
AB  - In the present study, bone carbonic anhydrase was isolated from ancient human
      bones and its characteristic features were determined. For this purpose, the
      skull bone of about 3000 years age was used. The purification was performed in
      four steps. Four different isoenzymes of CA, including outer peripheral, inner
      peripheral, integral, and cytosolic were purified and characterized. Affinity
      chromatography using Sepharose-4B-L-tyrosyn sulfanilamide as a support material
      was used in its purification. Two different methods were used for enzymatic
      activity determination: a) hydratase, and b) esterase methods. Bradford and
      Coomassie Brillant Blue methods were used for protein determination. Optimal pH,
      temperature, and molecular weight determinations were performed by conventional
      methods. The purification degree and the subunits, if present, were determined by
      SDS-PAGE. The effects of some chemicals on the enzyme were also investigated. The
      most cardinal finding was that the enzymatic activity has been found in antique
      human bone, showing some other enzymatic activity. That the alkaline phosphatase
      activity has been determined in the same sample supports the finding of carbonic
      anhydrase.

PMID- 11513095
TI  - Functional residues on the enzyme active site of glyoxalase I from bovine brain.
AB  - Bovine brain glyoxalase I was investigated in order to identify amino acid
      residues essential for its catalytic activity. This enzyme is a 44-kDa dimeric
      protein which exhibits a characteristic intrinsic fluorescence, with an emission
      peak centered at 342 nm. The total of eight tryptophan residues/molecule was
      estimated by using a fluorescence titration method. Low values of Stern Volmer
      quenching constants for the quenchers used indicated that the tryptophan residues
      are relatively buried in the native molecule. Similar results were obtained for
      glyoxalase I, purified from yeast and human erythrocytes. The activity of bovine
      brain glyoxalase I was found to be particularly sensitive to 2,3-butanedione and
      diethylpyrocarbonate, selective reagents for arginine and histidine residues,
      respectively. A minor effect was observed by treatment of the enzyme with other
      amino acid-specific reagents. A protective effect of the competitive inhibitor S
      hexylglutathione was observed for all reagents used, indicating the presence of
      modified amino acids in or near the enzyme active site.

PMID- 11513096
TI  - Creationism versus evolution, DSM style.

PMID- 11513097
TI  - Right and left handedness defined: a multivariate approach using hand preference
      and hand performance measures.
AB  - OBJECTIVE: The major aim of this study was to determine whether a combination of
      hand preference inventories and hand performance measures identifies distinct
      handedness groups. If distinct groups are identified, then these subgroupings can
      be used in future studies to learn more about the neurobiology of these distinct
      handedness groups. BACKGROUND: Although most individuals classify themselves as
      right- or left-handed, it is not entirely clear whether handedness should be
      determined based on preference inventories, hand performance tasks, or a
      combination of these measures. Given that hand preference is linked in part to
      hemispheric specialization of language, it is important to clearly define hand
      preference groups if lateralized differences between right- and left-handers are
      to be explored. Healthy adult right- and left-handers were examined from a
      multivariate perspective in an attempt to determine whether handedness subgroups
      exist within performance data. METHOD: Hand preference of 62 right- and left
      handed male and female adults was assessed using items from Briggs and Nebes' and
      Oldfield's handedness inventories. Individuals were assigned to right- and left
      hand preference groups, both by visually inspecting the distribution of
      preference scores and via cluster analysis. Asymmetries in performance of
      unimanual motor tasks (grooved pegboard, finger-tapping, and grip strength) were
      then examined using a multivariate approach. RESULTS: Sixteen items from the two
      handedness inventories were used to determine preference-based handedness groups.
      Two non-overlapping groups, right- and left-hand preference, were identified.
      Writing hand was highly correlated with hand-preference group, as only three
      individuals in the entire sample wrote with the non-preferred hand. The expected
      unimodal distributions of performance asymmetry scores, known as laterality
      quotients (LQs), were seen. However, when those LQs were viewed from a
      multivariate perspective, distinct performance-based groups emerged. In more than
      90% of the observed cases, the performance-based groups corresponded to
      preference-based groups. No sex differences were found; the relationship between
      preference and performance measures was not significantly different for men and
      women. CONCLUSIONS: Writing hand was highly correlated with scores from a hand
      preference inventory. In contrast, the use of a single hand performance measure,
      finger tapping or pegboard, did not always correctly classify an individual as
      right- or left-handed. However, when both of these hand performance measures were
      used together. individuals were correctly classified as right- or left-handed.
      Using this approach, two approximately non-overlapping groups, right- and left
      handers, emerged. Thus, handedness is probably not a one-dimensional trait or
      behavior, and must be defined using multiple measures that assess different
      aspects of hand preference and performance. The implications for hemispheric
      specialization of language and neural asymmetry research are discussed.

PMID- 11513098
TI  - Theory of mind and pragmatic abilities in dementia.
AB  - OBJECTIVE: "Theory of Mind" (ToM) is the capacity to attribute mental states to
      oneself and to others and to interpret behavior in terms of mental states.
      Deficits in both ToM and pragmatic abilities have been described in patients with
      neurologic disorders, such as frontal lobe lesions and right hemisphere strokes,
      but have not been assessed in demented patients. METHODS: This study examined ToM
      and pragmatic abilities in a consecutive series of 34 patients with probable
      Alzheimer disease (AD) using a second-order false belief story, 11 short stories
      assessing understanding of social situations, and a test of pragmatic abilities
      assessing both indirect requests and-conversational implications. RESULTS: Sixty
      five percent of AD patients with mild dementia could not pass a second-order
      false belief task, whereas no failures were found in a group of 10 age-comparable
      healthy controls. AD patients who did not pass the second-order false belief task
      had more severe deficits on tests of verbal anterograde memory, verbal
      comprehension, abstract thinking, and naming, as compared with AD patients who
      passed the task. AD patients also showed significantly more severe pragmatic
      deficits than age-comparable healthy controls, and there was a significant
      association between ToM and pragmatic deficits. On the other hand, there were no
      significant associations between ToM or pragmatic deficits, and behavioral
      problems frequently reported in AD such as depression, delusions, apathy, and
      irritability. CONCLUSIONS: This initial exploratory investigation demonstrated
      significant deficits in both ToM and pragmatic abilities in a consecutive series
      of AD patients with mild dementia.

PMID- 11513099
TI  - Route learning performance in Alzheimer disease patients.
AB  - OBJECTIVE: To examine performance on an objective measure of route learning in
      Alzheimer disease (AD) patients. BACKGROUND: Topographic disorientation (TD) is a
      common problem among AD patients. The underlying cognitive deficits that
      contribute to TD in AD patients are not well understood. METHOD: This study
      examined 19 healthy older individuals (controls) and 16 AD patients who were
      administered a comprehensive neuropsychological battery along with a novel Route
      Learning Test (RLT). Areas assessed included incidental learning, spatial
      relations. recall of the walking route, and recognition of landmarks. RESULTS:
      Despite comparable performance on basic visuospatial ability measures, AD
      patients performed significantly worse than controls on the RLT and evidenced
      poor incidental learning for environmental details. A measure of egocentric and
      allocentric orientation ability was the best predictor of RLT performance in AD
      patients. Among RLT subtests, AD patients performed best on recognition of
      landmarks compared with recognition and recall of spatial layout or recognition
      of incidental items in the environment. CONCLUSIONS: Our findings suggest that
      poor performance on the RLT in AD patients is characteristic of poor spatial
      orientation or spatial reasoning. Therefore, episodes of TD in AD patients may
      occur secondary to poor spatial orientation.

PMID- 11513100
TI  - Psychiatric outcome in patients with a psychogenic movement disorder: a
      prospective study.
AB  - OBJECTIVE: To assess psychiatric outcome in patients with an established
      diagnosis of a hyperkinetic (i.e. tremor, dystonia, myoclonus) psychogenic
      movement disorder. BACKGROUND: Longitudinal studies of patients with psychogenic
      movement disorders (PMD) have to date suffered from small sample size, lack of
      sample homogeneity (psychogenic movements grouped with other somatoform
      disorders, mixed hyper and hypokinetic movements), the absence of structured
      psychiatric interviews, and a failure to adequately address the extent of
      psychiatric co-morbidity by adopting a hierarchical approach to diagnosis.
      METHODS: A sample of 88 patients with documented PMD according to the criteria of
      Fahn and Williams were followed up on average 3.2 years (sd = 2.2; range 1-7
      years) after first being assessed at a tertiary referral clinic for patients with
      movement disorders. The detailed psychiatric assessment included the Structured
      Clinical Interview for Axis (SCID-I) and Axis II (SCID-II) DSM-IV disorders which
      generated diagnoses with respect to major mental illness (SCID-I) and personality
      disorders (SCID-II) respectively. RESULTS: Of 88 subjects initially seen in
      clinic, three had died (one by suicide), two were in nursing homes (Alzheimers
      disease, terminal cancer) and three had emigrated. Of the remaining 80 subjects,
      42 (52.5%) agreed to be interviewed. There were no demographic or illness-related
      differences between those who agreed or refused participation. At follow-up, the
      mean age of subjects was 48.6 (13.3) years, 62.7% were female and 75% were
      unemployed. An Axis I diagnosis of mental illness was made in 40 (95.3%)
      subjects. The PMD had remitted in four subjects, but had been replaced in two of
      them by a different mental disorder. Thirty-eight percent of subjects with PMD
      had developed additional unexplained medical symptoms at follow-up. Point and
      lifetime prevalence rates for other Axis I diagnoses were: major depression 19.1%
      and 42.9%; anxiety disorders 38.2% and 61.9%; co-morbid major depression and
      anxiety disorders 11.9% and 28.6%. Personality disorders were present in 45% of
      the sample. No subject viewed their PMD as primarily psychiatric in origin. Poor
      outcome with respect to the abnormal movements was associated with long duration
      of symptoms, insidious onset of movements and psychiatric co-morbidity on Axis I
      diagnoses. CONCLUSIONS: Follow-up data of patients with PMD revealed a
      persistence in abnormal movements in more than 90% of subjects. Prevalence rates
      of mental illness in excess of those found in the general population and in
      neurologic disorders plus an inability to acknowledge the essentially psychologic
      nature of their condition characterized the outcome picture and carries a poor
      longer term prognosis.

PMID- 11513101
TI  - Verbal fluency in mania: relationship to number of manic episodes.
AB  - OBJECTIVE: The objective of this study was to examine verbal fluency in a group
      of patients with bipolar disorder (BPD) during an acute episode of mania, and to
      determine whether performance was related to disease chronicity. We hypothesized
      that manic patients with BPD would be impaired on verbal fluency, and that this
      impairment would be greatest in those individuals who had experienced a greater
      number of manic episodes. METHOD: Forty-five manic inpatients with bipolar
      disorder, and 30 healthy volunteers completed tests of phonemic and semantic
      verbal fluency. The patients were dichotomized into those experiencing their
      first episode of mania (FE) and those who had experienced multiple episodes (ME).
      RESULTS: On the phonemic fluency task, ME patients produced significantly fewer
      words than both healthy volunteers and FE patients, and they made a greater
      number of errors. No significant group differences in overall output were found
      on the semantic fluency task, although the ME group was more error-prone than
      were the other groups. CONCLUSIONS: These findings suggest that verbal fluency is
      more impaired in ME patients than in patients who have experienced only a single
      manic episode.

PMID- 11513102
TI  - Neuropsychological symptoms associated with low-level exposure to solvents and
      (meth)acrylates among nail technicians.
AB  - OBJECTIVE: To evaluate reports of neuropsychological symptoms among women
      occupationally exposed to products commonly used in nail studios. BACKGROUND:
      Typical preparations found in nail studios contain a variety of organic solvents
      (e.g., toluene, acetone, formaldehyde) and (meth)acrylates with known neurotoxic
      properties. Little research has focused on the neuropsychological sequelae of
      exposure to these substances occurring in the cosmetics industry. METHOD:
      Participants included nail salon technicians (n = 150) and controls (n = 148).
      Nail technicians were compared with demographically similar controls using the
      Neuropsychological Impairment Scale, a self-reported measure of
      neuropsychological and psychological symptoms. Aspects of the workplace
      environment (e.g., square footage of the salon, adequacy of ventilation, hours
      worked) also were assessed. RESULTS: A MANOVA revealed small but significant
      differences in the overall level of symptoms as well as in individual scales
      measuring neurologic complaints, cognitive efficiency, memory, verbal learning,
      and academic skills (p < 0.001). Moreover, nail technicians were significantly
      more likely to score above the clinical cutoffs than were controls on four of the
      seven clinical scales and two of the three summary indices. Multiple regression
      analysis indicated that the severity of symptoms was associated with level of
      occupational exposure (p < 0.01). The cumulative impact of workplace size and
      ventilation were most strongly associated with symptom severity. CONCLUSIONS:
      Exposure to low-level neurotoxins common to nail studios results in the self
      reported experience of cognitive and neurologic symptoms similar to other types
      of solvent and (meth)acrylate exposure. The profile of reported symptoms is
      consistent with deficits typically observed in this type of neurotoxic exposure:
      neurologic complaints as well as perceived problems with cognitive efficiency,
      memory, and learning. Additionally, the nail technicians reported a higher
      overall level of complaints and greater severity of symptoms than did the
      controls.

PMID- 11513103
TI  - Temporary phantom limbs evoked by vestibular caloric stimulation in amputees.
AB  - OBJECTIVE: Relationships between the vestibular system and the body schema have
      been suggested but never demonstrated in amputees. We studied the effects of
      vestibular stimulation on body representation in amputees focusing on the phantom
      limb phenomenon. METHOD: Prospective study in 31 amputated subjects of one or
      several limbs before the age of 16 years. The amputees underwent a caloric
      vestibular stimulation test, ipsilateral (n = 31) and contralateral (n = 8) to
      the side of amputation. Amputees were asked to report their perceptions
      spontaneously and to answer open questions. Four types of perceptions were
      analyzed: normal phantom, deformed phantom, painful phantom, and no phantom,
      before, during, and after the vestibular stimulation test. Data were compared
      between the two groups for pre- and post-test perceptions (chi2 test). RESULTS:
      Vestibular caloric stimulation provoked temporary perception of a normal phantom
      limb in 16 of 17 amputees who previously did not experience phantoms. For 12 of
      12 amputees who currently experienced deformed or painful phantom limbs, caloric
      stimulation led to temporary replacement of the abnormal phantom with a non
      painful normal phantom. CONCLUSIONS: The phenomena observed: 1) throw light on
      assumed mechanisms controlling construction of static and dynamic engrams used to
      produce the body schema; 2) complete the neuromatrix theory proposed to explain
      the phantom limb phenomenon; and 3) suggest that the vestibular system triggers
      the procedure of reconstruction of the global body schema.

PMID- 11513104
TI  - Sneddon's syndrome: a cause of cognitive decline in young adults.
AB  - OBJECTIVE: To review the clinical, psychometric, laboratory, and radiologic
      findings of 6 patients with Sneddon's syndrome (SS) who presented with cognitive
      dysfunction rather than stroke. DESIGN AND METHODS: Case series. All patients
      fulfilled were diagnosed as SS based on the co-occurrence of livedo racemosa and
      neurologic disease. Patients presenting with clinical stroke were excluded.
      RESULTS: Patients presented with cognitive complaints at an early age and all
      noted skin lesions from 6 months to 10 years before onset of cognitive symptoms.
      Associated systemic disorders included hypertension and seizures. Laboratory
      evidence of a hypercoagulable condition was identified in 4 of 6 cases. Brain MRI
      scans demonstrated atrophy, especially in parieto-occipital regions and cerebral
      blood flow on brain SPECT scan was reduced in a similar distribution. CONCLUSION:
      Patients with SS can develop dementia without antecedent clinical stroke. While
      the specific pathogenic mechanism of dementia in SS remains speculative, the
      disease predominantly injures brain tissue in vascular "watershed" territories.

PMID- 11513105
TI  - Dependence of GC-RRTs on the electrical charge at substituents of chlorinated
      dioxins and related compounds.
AB  - The correlation between gas chromatograph relative retention times (GC-RRTs) of
      polychlorinated dioxins and related compounds (PCBs, PCDDs, PCDFs, and PCNs) and
      descriptors calculated from the electrical charges at substituents, such as the
      sums of the charges at hydrogen atoms (QH), and chlorine atoms (QCl), and the sum
      of QH and QCl (Qall), was analyzed for their congeners and isomers. The
      dependence of GC-RRTs on these descriptors varied dramatically. For the
      congeners, there was an approximately linear relationship between GC-RRTs and all
      the descriptors. For the isomers, although there was little significant
      relationships, by classifying GC-RRTs based on Nad-Cl or Nad-H defined from the
      number of adjacent chlorine and hydrogen substituents, a linear relationship
      between GC-RRTs and QH was found for CBs, CDDs, and CDFs, and GC-RRTs for CNs
      could be classified. From an analysis of the electrical charges at hydrogen
      substitutents bonded to adjacent and non-adjacent positions, the average-charge
      of such substituents bonded to adjacent positions decreased with an increase in
      Nad-H, and this tendency was similar to that for bonding to ortho-, meta-, para-,
      alpha-, and beta-positions.

PMID- 11513106
TI  - Dependence of GC-RRTs on the solvent-accessible surface area of dioxins and
      related compounds.
AB  - The correlation between gas chromatograph relative retention times (GC-RRTs) of
      dioxins and related compounds, polychlorinated biphenyls (PCBs), polychlorinated
      dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and
      polychlorinated naphthalenes (PCNs), and their solvent-accessible surface area
      (SAS) was analyzed for congeners and isomers. GC-RRTs were linearly dependent on
      SAS for congeners while there was little dependence for isomers. However, by
      using classification parameters, Nad-Cl, Nad-H, N1,9Cl, and NalphaCl, based on
      the substitution positions and patterns of chlorine and/or hydrogen atoms bound
      to the molecular skeleton, a linear relationship was found among isomers.
      Furthermore, the GC-RRTs of CDD, CDF, and CN isomers, which are planar, decreased
      despite increasing SAS, and this tendency was enhanced with the above
      classification. The retention behavior was explained in terms of the effective
      enhancement of molecular hydrophobicity caused by an increase in the number of
      adjacent chlorine pairs.

PMID- 11513107
TI  - Hydrolysis of chlorpyrifos in natural waters of the Chesapeake Bay.
AB  - Chlorpyrifos is the most widely used insecticide in the Chesapeake Bay region.
      Recent studies show that this organophospate chemical is consistently present in
      the air, rain and surface waters of the Chesapeake Bay region, suggesting a long
      environmental half-life. Hydrolytic degradation of chlorpyrifos is likely a
      dominant removal process, but existing hydrolysis data do not reflect conditions
      in the Chesapeake Bay. In this project, hydrolysis rates of chlorpyrifos were
      measured in sterilized, ambient water from the mouth of four Chesapeake Bay
      tributaries ranging in salinity from 0 to 17 ppt. The measured hydrolysis half
      lives varied from 24 d in the Patuxent River to 126 d in the Susquehanna River.
      These results indicate that pH alone cannot be used as a single parameter to
      predict hydrolysis under field conditions. The influence of copper concentration,
      and other water constituents, need to be further evaluated as they may emerge as
      independent predictors to assess the fate of pesticides in natural systems.

PMID- 11513108
TI  - GC/MS analysis of polybrominated diphenyl ethers in fish collected from the
      Inland Sea of Seto, Japan.
AB  - Development of an analytical method for polybrominated diphenyl ethers (PBDEs) in
      fish and their concentration in Japanese marine fish were investigated. Fish
      homogenate was extracted with diethyl ether/hexane (1 + 3). The extract was
      cleaned up by automated gel permeation chromatography (GPC) and then by mini
      column chromatography, which consisted of three layers of silica gel and sulfuric
      acid-impregnated silica gel. The PBDE fraction was concentrated and injected into
      a GC/MS with negative chemical ionization (NCl). Recoveries of the 15 individual
      PBDEs (BDE-15, 28, 37, 47, 66, 71, 75, 77, 85, 99, 100, 119, 153, 154, and 209)
      each at a fortification level of 4 ng/g lipid were in the range of 88-128% and
      the relative standard deviations (RSD) were 0.43-7.6% (n = 4). Seven species of
      marine fish (conger eel, flounder, gray mullet, horse mackerel, red sea bream,
      sea bass, and yellowtail) were collected from the Inland Sea of Seto, and were
      analyzed with the developed method. Seven PBDEs (BDE-28, 47, 66, 99, 100, 153,
      and 154) were detected in all the samples. The most abundant PBDE congener was
      BDE-47 found in all the samples. Relatively high levels of PBDEs were found in
      the gray mullets and yellowtails.

PMID- 11513109
TI  - Polychlorinated dibenzo-p-dioxins and dibenzofurans in paper making from a pulp
      mill in China.
AB  - An extensive investigation on the input, formation and fate of PCDD/Fs in a pulp
      mill using reeds as raw materials in China was carried out. The main PCDD/Fs
      input in the production process came from reeds, which may be contaminated by
      PCDD/Fs from sodium pentachlorophenate to control snailborne schistosomiasis.
      High levels of I-TEQ in the products were observed.

PMID- 11513110
TI  - Iron-mediated reactions of polychlorinated biphenyls in electrochemical
      peroxidation process (ECP).
AB  - A study was conducted to explore some of the basic processes of polychlorinated
      biphenyl (PCB) destruction by a new technology termed electrochemical
      peroxidation process (ECP). ECP represents an enhancement of the classic Fenton
      reaction (H2O2 + Fe2+) in which iron is electrochemically generated by steel
      electrodes. Focus was on the extent of adsorption of a mixture of Aroclor 1248 on
      steel electrodes in comparison to iron filings. Commercially available zero
      valent iron filings rapidly adsorbed PCBs from an aqueous solution of Aroclor
      1248. Within 4 h, all the PCBs were adsorbed at 1%, 5%, and 10% Fe0 (w/v)
      concentrations. Little difference in adsorption was found between acidic (2.3)
      and unamended solutions (pH 5.5), even though significant differences in iron
      oxidation state and Fe2+ concentrations were measured in solution. PCB adsorption
      also occurs on steel electrodes regardless of the pH or electric current applied
      (AC or DC), suggesting the combination of oxidizing (free radical-mediated
      reactions) and reducing (dechlorination reactions) iron-mediated degradation
      pathways may be possible. Extraction of the iron powder after 48 h of contact
      time yielded the progressive recovery of biphenyl with increasing Fe mass(from
      0.4% to 3.5%) and changes of the PCB congener-specific pattern as a consequence
      of dechlorination. A variety of daughter congeners similar to those accumulated
      during anaerobic microbial dechlorination of Aroclor 1248 in contaminated
      sediments indicate preferential removal of meta- and para-chlorines.

PMID- 11513112
TI  - Determination of polybrominated diphenyl ethers and PBDD/Fs during the recycling
      of high impact polystyrene containing decabromodiphenyl ether and antimony oxide.
AB  - A high impact polystyrene (HIPS) plastic, flame retarded with decabromodiphenyl
      ether (DecaBDE) and antimony trioxide (Sb2O3) has been repeatedly processed and
      the amount of debromination of the flame retardant and possible formation of
      PBDD/F was monitored. No indications of debromination were found. The reprocessed
      (recycled) plastic was found to comply with the German Chemicals Banning
      Ordinance. The concentrations of relevant PBDD/F congeners were at least one
      order of magnitude below the regulated limit values for PBDD/F (1 ppb for the sum
      of four congeners, 5 ppb for the sum of all eight regulated congeners).

PMID- 11513111
TI  - Dioxins in adipose tissue of non-occupationally exposed persons in France:
      correlation with individual food exposure.
AB  - We evaluated individual adipose tissue (subcutaneous lipomas) dioxin
      contamination in non-occupationally exposed persons living in France (adult
      patients undergoing a surgical ablation of benign lipomas), in relation to the
      corresponding individually evaluated mean daily dietary dioxin intake (DDDI). The
      diet survey (questionnaire) included information on consumption of meat, fish,
      milk and dairy products, from which the individual DDDI was calculated. Sixteen
      subjects participated in this study. DDDI ranged between 1.06 and 3.31 pg I
      TEQ/kg body weight, bw (mean value: 2.05+/-0.72). Adipose tissue polychlorinated
      dibenzo-p-dioxins (PCDD)/polychlorinated dibenzofurans (PCDF) levels ranged
      between 18.5 and 76.9 pg I-TEQ/g lipids (mean value: 35.6+/-14.8). No relation
      was found between the DDDI and adipose tissue PCDD/PCDF concentrations. The mean
      DDDI in France does not fundamentally differ from those found in other
      industrialised countries, is within the range of 1-4 pg I-TEQ/kg/day recently
      suggested by WHO-ECEH/ICPS for the tolerable daily intake of dioxins. Adipose
      tissue PCDD/PCDFs levels are similar to levels in other European countries and
      USA without relation to sex or age, and can be considered representative European
      background concentrations. Globalisation of alimentary production leads to a
      similar food exposure in Western European countries, in spite of dioxins
      accidental selective contaminations that are epiphenomenon and thus do not have
      any impact in human dioxin background levels.

PMID- 11513113
TI  - Formation of polychlorinated dibenzo-p-dioxins/dibenzofurans from residual carbon
      on municipal solid waste incinerator fly ash using Na37Cl.
AB  - Na37Cl was used to study the role of chlorine in the formation of polychlorinated
      dibenzo-p-dioxins (PCDD) and dibenzofurans (PCDF) from carbon. Adding Na37Cl to
      fly ash showed that this compound was a (relatively) poor chloride source;
      chlorine naturally present on the ash - which could include both chlorine in
      residual carbon and (metal) chlorides - was found to be ca. 17x more reactive.
      When both Na37Cl and CuCl2 were added to aqueous extracted fly ash, the
      percentage of 37Cl from Na37Cl included in PCDD/F increased, compared to the
      combination of Na37Cl/fly ash. When Na37Cl and CuCl2 were exchanged in water,
      followed by evaporation of the solvent, and mixed with aqueous extracted fly ash,
      the percentage of 37Cl included in PCDD/F was much higher. Apparently, direct
      transfer of 37Cl from CuCl2 to carbon and PCDD/F was much faster than transfer of
      37Cl- from Na37Cl via a metal chloride (such as CuCl2) to carbon and PCDD/F. In
      addition to chlorine in PCDD/F originating from exchanged NaCl/CuCl2, chloride
      left on the fly ash after aqueous extraction and chlorine present in residual
      carbon could also have been incorporated in PCDD/F.

PMID- 11513114
TI  - Quantitative structure-property relationship studies on n-octanol/water
      partitioning coefficients of PCDD/Fs.
AB  - Based on some fundamental quantum chemical descriptors computed by PM3
      Hamiltonian, by the use of partial least-squares (PLS) analysis, a significant
      quantitative structure-property relationship (QSPR) model for logKow of
      polychlorinated dibenzo-p-dioxins and dibenzo-p-furans (PCDD/Fs) was obtained.
      The QSPR can be used for prediction. The intermolecular dispersive interactions
      and thus the bulkness of the PCDD/Fs are the main factors affecting the logKow.
      The more chlorines in the PCDD/F molecule, the greater the logKow values.

PMID- 11513115
TI  - Chlorinated persistent organic pollutants in black-tailed gulls (Larus
      crassirostris) from Hokkaido, Japan.
AB  - Concentrations and patterns of several chlorinated persistent organic pollutants
      (POPs) including polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs)
      and biphenyls (PCBs) and DDTs, HCHs, CHLs and HCB were determined in black-tailed
      gulls (Larus crassirostris) from breeding grounds in Hokkaido, Japan.
      Subcutaneous fat of five adult gulls was analyzed, which had different
      concentrations of target compounds, whereas gull eggs contained similar
      concentrations of target compounds. Similar congener profiles were found between
      adult gulls and eggs. The concentrations of non-ortho PCBs varied from 3.4 to
      13.5 ng/g lipid weight (lw) in the fat of black-tailed gulls and from 2.4 to 7.4
      ng/g lw in their eggs. 2,3,7,8-PCDD/Fs occurred at relatively lower
      concentrations than non-ortho PCB congeners in both adult gulls and eggs. The
      total TEQs (toxic equivalents, PCDD/Fs+ non-ortho PCB) ranged from 0.26 to 1.0
      ng/g lw in adult gulls and ranged from 0.19 to 0.58 ng/g lw in eggs.

PMID- 11513116
TI  - Levels of polychlorinated dibenzo-p-dioxins and dibenzofurans in soil samples
      from Spain.
AB  - Soil analyses were carried out to evaluate the contamination caused by PCDDs and
      PCDFs in different soil samples. Monitoring was undertaken at different locations
      throughout Spain, from 1993 to 1999. A total of 230 samples were analysed. The
      levels ranged from 0.10 pg I-TEQ/g to 1.08 ng I-TEQ/g. Differences in dioxin
      levels were observed as a function of the sampling site, with levels at the
      industrial sites exceeding those at the control sites.

PMID- 11513117
TI  - Formation of PCDDs and PCDFs during the combustion of polyvinylidene chloride.
AB  - In laboratory-scale combustion of polyvinylidene chloride (PVDC) with a quartz
      tubular furnace designed and fabricated to provide the desired combustion
      temperature and mixing state of combustion gas with air, it was found that at 800
      degrees C or higher the level of polychlorinated dibenzo-p
      dioxins/polychlorinated dibenzofurans [corrected] (PCDDs/PCDFs) resulting from
      PVDC combustion was no higher than that from heating air alone, and thus far
      below the levels which resulted from PVDC combustion at 750 degrees C or lower.
      The results provide the first laboratory confirmation of the relation between
      PVDC incineration temperature and PCDD/PCDF formation, and of the primary
      importance of high temperature, turbulence for mixing between air and combustion
      gas, and sufficient residence time, as governing factors for the minimization of
      PCDD/PCDF formation in municipal solid waste incinerators.

PMID- 11513118
TI  - A reproducible approach to the reporting of organochlorine compounds in
      epidemiologic studies.
AB  - A growing body of research indicates that the most biologically active PCB
      congeners and organochlorines are not the most abundant components in human and
      wildlife samples. As researchers attempt measurement on a wider pool of less
      abundant compounds, they inevitably face quantification problems. To address this
      problem and enhance comparability across studies, we propose a standardized
      approach to report organochlorines that is based on a reproducible method to
      determine the limit of quantification (LQ). Two statistical methods are
      incorporated into our approach, one by Gibbons termed the Alternative Minimum
      Level (AML), and one based on determining a region of stable relativestandard
      deviation in instrument response (RSD). We illustrate our approach using
      historical samples collected during the 1960s from a cohort of pregnant women
      enrolled in the Child Health and Development Study. The results are applicable to
      determining the LQ of any method, and are of utmost importance to environmental
      scientists conducting trace organic analyses of complex mixtures. Our results
      demonstrate that: (1) precision as measured by RSD is the most important
      criterion in determining LQ; (2) the AML routinely isolates a region of constant
      RSD; and (3) the precision of the instrument detector response as measured with
      pure standards locates the LQ applicable for real samples - that is, the true
      limits of quantification reside in the detector, not the matrix effects or
      analyte recoveries associated with real samples. A corollary of these findings is
      that bias due to matrix effects and analyte recoveries can be assessed separately
      from precision and LQdetermination. Previous approaches involved spiking matrix
      blanks to determine LQ, a problematic strategy for real world, complex matrices.
      We have now validated the use of pure standards in LQ determination, an approach
      that is practical and accessible to most analysts.

PMID- 11513119
TI  - Distribution characteristics of PCBs in the sediments of the lower Nakdong River,
      Korea.
AB  - The objective of this study is to investigate the distribution characteristics of
      polychlorinated biphenyl (PCB) congeners in sediments of the lower Nakdong River
      of Korea. The sediments were collected using a grab sampler in May 1999. PCBs
      were extracted in the Soxhlet extractor and cleaned by using adsorption
      chromatographic techniques and concentrated sulfuric acid. A HP6890 gas
      chromatograph equipped with an electron capture detector was used for
      quantification. The results of congener specific analysis showed that the total
      concentration is ranged over 1.1-141 ng/g dry weight. The levels of PCB congeners
      are significantly correlated with the total organic carbons (TOC) in the
      sediments. The major fractions of PCBs in these sediments are congeners
      containing 4, 5 or 6 chlorine atoms per biphenyl molecule.

PMID- 11513120
TI  - Reductive dechlorination of polychlorinated biphenyls as affected by sediment
      characteristics.
AB  - The effect of sediment sources on the selection of polychlorinated biphenyl (PCB)
      dechlorinating competence was investigated using sediments from two different
      locations, the Grasse River and Owasco Lake. These two sediments had a similar
      organic carbon content but different particle size distribution. The two PCB-free
      sediments were spiked with Aroclor 1248 and inoculated with microorganisms from
      the Reynolds and General Motors sites in the St. Lawrence River, which exhibited
      different dechlorination patterns. When each inoculum was serially transferred
      into fresh sediments four times (every 8-10 weeks), they still maintained the
      initial dechlorination patterns regardless, the source of sediments and the
      number of transfers, and dechlorination patterns of the two inocula in the same
      sediments did not converge. In a parallel approach, when the acclimated
      microorganisms from the Reynolds site were inoculated into fresh sediments from
      both sources as well as sediments enriched with organic carbon (2%, w/v), the
      dechlorination pattern remained unchanged after a 40-week incubation. These
      results suggest that the sediment characteristics or organic carbon content did
      not play a role in the selection of dechlorinating populations.

PMID- 11513121
TI  - Progressive study and robustness test of QSAR model based on quantum chemical
      parameters for predicting BCF of selected polychlorinated organic compounds
      (PCOCs).
AB  - Systematic analyses on the effects of chemical structures of 31 polychlorinated
      organic compounds (PCOCs) on their bioconcentration behavior in rainbow trout
      (Oncorhynchus mykiss) were conducted using quantitative structure-activity
      relationship (QSAR) techniques. The cluster analyses of individual variables as
      well as the quality control chart of QSAR model implies the existence of
      outliers, while the simulation model excluding such samples showed an extreme
      robustness even if it was tested with different methods. Furthermore, the quantum
      chemical parameters entering into QSAR model were used to describe the
      bioconcentration pathways, and the results indicated that bioconcentration
      behaviors of selected compounds were complicated processes involving permeation
      stages as well as bio-chemical reaction stages.

PMID- 11513122
TI  - Formation of PCDF, PCDD, PCB, and PCN in de novo synthesis from PAH: mechanistic
      aspects and correlation to fluidized bed incinerators.
AB  - The difference of polychlorinated dibenzofurans (PCDF) isomer patterns between
      stoker type incinerators and some fluidized bed incinerators (FBI) is a key to
      understand the formation mechanisms in both types of incinerators. The total
      yield and the isomer patterns of PCDF, polychlorinated biphenyls (PCB),
      polychlorinated naphthalenes (PCN), and polychlorinated benzenes (PCBz) formed
      via de novo synthesis from polycyclic aromatic hydrocarbons (PAH) indicate that
      chlorinated aromatics in the FBI are formed as a result of PAH breakdown. The
      detailed analysis of the isomer patterns of PCDF, PCB and PCN gives a first
      insight into the transformation mechanism of the PAHs and the sequence of
      degradation, chlorination and oxygen insertion. The major chlorination takes part
      at the position of the C-C cleavage during degradation of the PAHs. Further
      chlorination of the hydrogen position of the former PAH takes part preferably in
      ortho-position to this chlorination or is directed by incorporated oxygen. A
      perylene structure in soot is proposed as basis for the observed PCDF pattern in
      the FBI. Polychlorinated dibenzo-p-dioxins (PCDD) and polychlorinated phenols
      (PxCP) were formed in lower concentrations from the de novo experiments
      indicating an additional formation pathway for these compounds in the FBI.

PMID- 11513123
TI  - Separation of PCBs and PAHs in sediment samples using silica gel fractionation
      chromatography.
AB  - The aim of this research is to develop a silica gel fractionation procedure for
      sediment sample extracts, which separates polycyclic aromatic hydrocarbons (PAHs)
      and polychlorinated biphenyls (PCBs) into two groups, while simultaneously
      eliminating most interfering substances for subsequent instrumental analysis.
      This is achieved by optimizing the fraction cut-off volume of eluting solvent and
      the deactivation level of the silica gel. Using fully activated silica gel and
      cutting off PCB collection after passing 60-65 ml eluting solvent (pentane or
      hexane) through the column resulted in satisfactory separation of PCBs and PAHs.
      This procedure tends to have a higher reliability for PCBs and PAHs with higher
      molecular mass. This approach deviates only slightly from the standard methods of
      the USEPA, and it is less expensive due to reduced sample pre-treatment time and
      solvent consumption.

PMID- 11513124
TI  - Evaluation of TCDD biodegradability under different redox conditions.
AB  - Polychlorinated dibenzo-p-dioxins have been generated as unwanted by-products in
      many industrial processes. Although their widespread distribution in different
      environmental compartments has been recognized, little is known about their fate
      in the ultimate environment sinks. The highly stable dioxin isomer 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD) has been called the most toxic compound known
      to man. In this laboratory microcosm study, TCDD bioavailability was evaluated
      under five reduction/oxidation (redox) conditions including aerobic
      biodegradation, aerobic cometabolism, methanogenesis, iron reduction, and
      reductive dechlorination. Activated sludge and aquifer sediments from a TCDD and
      a pentachlorophenol (PCP) contaminated site were used as the inocula. Acetate,
      sludge cake, and cane molasses were used as the primary substrates (carbon
      sources) in cometabolism and reductive dechlorination microcosms. After a 90-day
      incubation period, microcosms constructed under reductive dechlorination
      conditions were the only treatment showing promising remediation results. The
      highest TCDD degradation rate [up to 86% of TCDD removal (with an initial
      concentration of 96 microg/kg of soil)] was observed in the microcosms with
      anaerobic activated sludge as the microbial inocula and sludge cakes as the
      primary substrates. Except for reductive dechlorination microcosms, no
      significant TCDD removal was observed in the microcosms prepared under other
      conditions. Thus, application of an effective primary substrate to enhance the
      reductive dechlorination process is a feasible method for TCDD bioremediation.
      Bioremediation expense can be significantly reduced by the supplement of some
      less expensive alternative substrates (e.g., sludge cakes, cane molasses).
      Results would be useful in designing a scale-up in situ or on-site bioremediation
      system such as bioslurry reactor for field application.

PMID- 11513125
TI  - Survey of PCDD/Fs and non-ortho PCBs in UK sewage sludges.
AB  - A survey of PCDD/F and non-ortho PCB concentrations in the mesophilic,
      anaerobically digested sludge of 14 UK wastewater treatment works was carried
      out. The range of total Cl1-Cl8DD/F concentrations in the sludges was 8880-428000
      pg/g dw with a median of 23300 pg/g dw. The concentrations of the three non-ortho
      PCBs were in the range 272-63000 pg/g dw with a median of 695 pg/g dw. The PCDD/F
      I-TEQs of the sludges studied were comparable to those published in the
      literature with a range of 20-225 pg I-TEQ/g dw and a median of 40.4 pg/g dw. The
      non-ortho PCBs usually added 2-7 pg/g to the total TEQ with one notable exception
      which increased the TEQ value 20-fold. With three exceptions, the PCDD/F content
      of the sludges fell well below the draft EU limit values proposed on 27 April
      2000. The homologue group pattern of the PCDD/Fs is dominated by the HpCDDs and
      OCDD and is consistent with that found in most sewage sludges. There appears to
      be no correlation between the degree of industrial input and the PCDD/F
      concentration. This suggests that trade effluent is not always the most
      significant source of PCDD/Fs to wastewater in the UK.

PMID- 11513126
TI  - Identification and quantification of polychlorinated biphenyls and some endocrine
      disrupting pesticides in human adipose tissue from Finland.
AB  - Organochlorine pesticides and polychlorinated biphenyls (PCBs) were analysed in
      extracts of human adipose tissue. The samples consisted of abdominal, mammary,
      and perirenal fat tissue of 27 Finnish adult males and females. Lipids were
      separated from the low-molecular compounds by preparative gel permeation
      chromatography (GPC) and the extracts were further cleaned-up using Florisil
      chromatography. The compounds were analysed in the extracts by gas chromatography
      (GC) using electron capture detection and by GC-mass spectrometry in the selected
      ion monitoring mode. Of the 23 analysed pesticide residues only seven could be
      detected in the extracts. All the extracts contained the DDT metabolite 4,4'-DDE,
      hexachlorobenzene, and PCBs. Other compounds found in the extracts were 4,4'-DDT,
      4,4'-DDD, pentachlorobenzene, and beta- and gamma-hexachlorocyclohexane (HCH).
      The antiandrogenic 4,4'-DDE was the most abundant pesticide with concentration
      levels ranging from 3.5 to 3229 ng/g lipids (ppb). The mean concentration of DDE
      was 567 ppb, of pesticides in all 1008 ppb and of PCBs 504 ppb. Several of the
      identified compounds have been shown to exhibit endocrine disrupting effects.
      Statistical analysis showed a positive age correlation of DDE in females and
      hexachlorobenzene in males. No statistically significant differences were found
      for concentrations of individual compounds between sexes.

PMID- 11513127
TI  - Atmospheric deposition of polychlorinated dibenzo-p-dioxins, polychlorinated
      dibenzofurans, and dioxin-like polychlorinated biphenyls in the Kanto Region,
      Japan.
AB  - The atmospheric bulk (dry and wet) deposition of dioxins was investigated at four
      locations (Tokyo, Yokohama, Tsukuba, and Tanzawa) in the Kanto region (in Japan)
      over one year using a stainless-steel pot. Annual average polychlorinated dibenzo
      p-dioxins/polychlorinated dibenzofurans (PCDD/PCDF) deposition fluxes were
      estimated to be from 450 to 1300 ng/m2/yr, and the annual average TEQ fluxes from
      5.7 to 17 ng-TEQ/m2/yr at the four locations. The PCDD/PCDF deposition flux was
      higher in winter than in summer. The deposition flux could be related to ambient
      temperature, particularly for less chlorinated PCDDs/PCDFs, while the deposition
      flux is not necessarily related to the amount of precipitation. The PCDD/PCDF
      deposition flux increased as the particle deposition flux increased, for the
      winter samples. Based on the ratio of the PCDD/PCDF deposition fluxes to the
      particle deposition fluxes, the contribution of the reentrainment of soil
      particles to the TEQ of PCDD/PCDF deposition was considered to be negligible in
      this region. Based on the air concentrations monitored near our deposition
      sampling points by the municipalities, the ratio of the annual deposition flux to
      the annual average air concentration was roughly estimated to be 0.082 cm/s. The
      range of deposition flux in the Kanto region was estimated to be from 1.5 to 31
      (median: 9.8) ng-TEQ/m2/yr based on the range of air concentration data measured
      by the municipalities. The total annual deposition flux in the entire Kanto
      region was estimated to range from 50 to 900 g-TEQ/yr (median 320 g-TEQ/yr). This
      estimated flux was of the same order as the sum of estimated emissions from
      municipal solid waste incinerators and industrial waste incinerators in the Kanto
      region. The contributions of dioxin-like PCBs in Yokohama, Tsukuba, and Tanzawa
      depositions were less than 10% of the total TEQ; however, in Tokyo it was almost
      equal to or more than 50%.

PMID- 11513128
TI  - A simple kinetic model of PCDD/F formation by de novo synthesis.
AB  - A simple fixed-bed reactor model is used to describe experimental data about the
      formation of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/F) from
      fly ash carbon. The heterogeneous oxidation of graphite-like carbon is
      represented by a reaction which is first order in carbon and one half order in
      oxygen. The same orders of reaction are assumed to be valid for PCDD/F formation,
      such that the oxidation of fly ash carbon would have three parallel channels
      leading to COx, PCDD and PCDF. In addition, PCDD/F degradation by oxygen is
      considered and appropriate rate constants were fitted to simulate the
      experimental data. The effects of water vapour and particulate copper on PCDD/F
      formation are included. As a result, an overall kinetic model of PCDD/F formation
      is obtained which describes most of the experimental data with reasonable
      accuracy. The main reaction channel, COx formation, needs to be understood more
      completely, in order to interpret PCDD/F reaction pathways better. The model can
      be extended to include other chlorinated aromatics and the gas/particle
      partitioning of the semivolatiles. It provides a basis for the qualitative and
      quantitative interpretation of fixed-bed and flow reactor results and it is hoped
      to be applicable to industrial installations like waste incinerators and metal
      smelters.

PMID- 11513129
TI  - Chemical kinetic modeling of de novo synthesis of PCDD/F in municipal waste
      incinerators.
AB  - A kinetic model is developed for de novo synthesis of PCDD/F from carbon in
      incinerator fly ash. The main mechanistic steps considered in the model are
      carbon gasification, PCDD/F formation, desorption and degradation. Rate equations
      are derived which can relate PCDD/F formation with process variables including
      carbon concentration of fly ash, partial pressure of oxygen, reaction temperature
      and time. The kinetic model has been verified using laboratory de novo synthesis
      data reported in the literature. When the model is applied to industrial
      incinerator conditions, PCDD/F formation levels of 0.1-0.5 microg/N m3 in the gas
      phase and 0.1-1.2 microg/g in the solid phase are calculated, and both are in
      good agreement with incinerator measurements.

PMID- 11513130
TI  - Correlation of polychlorinated naphthalenes with polychlorinated dibenzofurans
      formed from waste incineration.
AB  - Isomer composition of polychlorinated naphthalenes (PCNs) was measured for
      municipal waste incinerator fly ash samples and for emission samples produced
      from soot and copper-deposit experiments conducted at the United States
      Environmental Protection Agency (US-EPA). Two types of PCN isomer patterns were
      identified. One pattern contained specific PCN isomers in which chlorine atoms
      are substituted as if the peri(alpha-) position were dechlorinated from the
      higher chlorinated PCNs one by one. In another pattern, the isomers had a
      tendency for the chlorine atoms to assume successive positions on the naphthalene
      ring, which may be caused by specifically oriented chlorination. Some of these
      isomers increased, together with several polychlorinated dibenzofuran (PCDF) and
      a few polychlorinated dibenzo-p-dioxin (PCDD) isomers. The ratios between some
      specific PCN, PCDF, and PCDD isomers measured for the fly ash samples agree with
      those obtained from the soot and copper-deposit experiments. The observations
      suggest that these isomers were formed possibly from de novo synthesis utilizing
      the carbon structure contained in soot under the catalytic effect of a copper
      compound. Typical isomers for PCNs and PCDFs produced from incineration emissions
      were identified.

PMID- 11513131
TI  - Catalyzed dehalogenation of Delor 103 by sodium hydridoaluminate.
AB  - The complete dechlorination of PCB liquid Delor 103 (42.6% Cl) to biphenyl has
      been effected in toluene with sodium dihydridobis(2-methoxyethoxo)aluminate
      (SDMA) in the presence of catalytic amounts of Ni(II) and Co(II) 2,4
      pentanedionates at elevated temperatures. Changes in PCB congeners distribution
      during dechlorination were monitored by GC(ECD) and GC/MS, and the scheme of
      their transformation was proposed on the basis of site selectivity observed. A
      kinetic analysis of the reaction is presented.

PMID- 11513132
TI  - Specificity and function of activating Ly-49 receptors.
AB  - Inhibitory Ly-49 receptors allow murine natural killer (NK) cells to kill cells
      with aberrant class I MHC expression while sparing normal cells. This is
      accomplished by their recognition of specific class I MHC products and prevention
      of NK-cell lysis of cells that present a normal repertoire of class I MHC ligands
      -"the missing self hypothesis". However, Ly-49 receptors that lack the
      cytoplasmic immunoreceptor tyrosine-based inhibitory motif, which is required for
      inhibition of killing, have also been described. These receptors were found to
      stimulate NK killing and are therefore referred to as activating Ly-49 receptors.
      Interestingly, the activating receptors have class I MHC-binding domains that are
      nearly indistinguishable from those of the inhibiting receptors, and binding to
      class I MHC has now been demonstrated for three activating receptors. Presently,
      there is no defined physiological role for activating Ly-49 receptors. Here we
      present an overview of current knowledge regarding the diversity, structure and
      function of activating Ly-49 receptors with a focus on class I MHC specificity,
      and we discuss their potential role(s) in natural resistance.

PMID- 11513133
TI  - Murine natural killer cell activation receptors.
AB  - Natural killer (NK) cells express two types of receptors involved in target
      recognition: inhibitory receptors for target cell MHC class I molecules and
      activation receptors. While there has been significant progress in understanding
      the inhibitory receptors, less is known about the activation receptors. Detailed
      analysis of several mouse NK-cell activation receptors provides insight into the
      physiologic relevance of these receptors in the innate immune response.

PMID- 11513134
TI  - Physiologic functions of activating natural killer (NK) complex-encoded receptors
      on NK cells.
AB  - Natural killer (NK) cells express a superfamily of surface proteins that share
      common structural features: dimeric type II integral membrane proteins with
      extracellular domains resembling C-type lectins. These receptors are encoded by a
      single genetic region called the NK complex (NKC). The NKC encompasses several
      families of genes including NKR-PI, Ly-49, CD94/NKG2, and NKG2D. Different NKC
      encoded receptors have been shown to activate or to inhibit NK-cell function, and
      different receptors within the same family can have opposing functions. Within an
      individual NK cell, inhibitory receptors typically predominate over stimulatory
      receptors, calling into question the teleologic requirement or physiologic
      significance of lectin-like activating receptors in NK cells. Despite the
      widespread expression of inhibitory receptors, however, subtle features of
      activating receptor biology enable them to stimulate effector functions in vivo
      and in vitro. Activating receptors and inhibitory receptors differ in their
      subset expression, in their structural constraints for binding to common ligands,
      in their ligand repertoires, and in that divergent families of activating
      receptors utilize different signaling pathways. These subset, binding,
      repertoire, and signaling diversities may allow activating receptors to manifest
      their effects in spite of inhibitory receptor functions during pathologic
      conditions in vivo. In this review, we will present a detailed analysis of the
      data supporting this hypothesis with particular relevance toward physiologic NK
      cell functions.

PMID- 11513135
TI  - Ligand interactions by activating and inhibitory Ly-49 receptors.
AB  - Natural killer (NK) cells express families of homologous receptors, members of
      which either activate or inhibit NK cells. We demonstrate that mouse Ly-49D is an
      activating receptor for the MHC antigen H2-Dd, which is also a ligand for the
      related inhibitory receptor Ly-49A. To compare and contrast their interactions
      with class I MHC ligand, we studied each of these receptors expressed in a rat NK
      cell hne, RNK-16, for their capacity to recognize wild-type or mutated H2-Dd. Our
      studies with Ly-49A reveal that functional interaction with H2-Dd depends on
      residues in the floor of the H2-Dd peptide-binding groove. The recent co-crystal
      of Ly-49A with H2-Dd indicates that these are not contact residues, thus they may
      contribute to allelic specificity through conformational changes in H2-Dd. We
      found that structural requirements for functional recognition of H2-Dd by Ly-49D
      differ markedly from those for recognition by Ly-49A. We note that H2-Dd
      expression on certain target cells is not sufficient to activate lysis mediated
      by Ly-49D, though the additional requirements for functional interaction are not
      yet identified. Here we review recent studies of Ly-49 receptor ligand
      specificities and their molecular basis. The functions of these related receptors
      with opposing functions and shared allospecificity remains unclear.

PMID- 11513136
TI  - Rat natural killer cell receptor systems and recognition of MHC class I
      molecules.
AB  - Rat natural killer (NK) cells recognize MHC-I molecules encoded by both the
      classical (RT1-A) and non-classical (RT1-C/E/M) MHC class I (MHC-I) regions. We
      have identified a receptor, the STOK2 antigen, which belongs to the Ly-49 family
      of killer cell lectin-like receptors, and we have localized the gene encoding it
      to the rat natural killer cell gene complex. We have also shown that it inhibits
      NK cytotoxicity when recognizing its cognate MHC-I ligand RT1-A1c on a target
      cell. This is the first inhibitory Ly-49-MHC-I interaction identified in the rat
      and highlights the great similarity between rat and mouse Ly-49 receptors and
      their MHC ligands. However, the mode of rat NK-cell recognition of target cells
      indicates that positive recognition of allo-MHC determinants, especially those
      encoded by the RT1-C/E/M region, is a prevalent feature. NK cells recruited to
      the peritoneum as a consequence of alloimmunization display positive recognition
      of allodeterminants. In one case, NK cells activated in this way have been shown
      to be specific for the immunizing, non-classical class I molecule RT1-Eu. These
      findings show that allospecific NK cells sometimes show features reminiscent of
      the adaptive immune response.

PMID- 11513137
TI  - Ligands for natural killer cell receptors: redundancy or specificity.
AB  - Several inhibitory and activating receptors involved in natural killer cell
      activation have been characterized. The increasing knowledge about their ligands,
      including classical MHC class I molecules, non-classical MHC class I molecules
      and MHC class I-related molecules, is shedding new light on the targets of innate
      immune recognition. While classical MHC class I molecules are constitutively
      expressed, some MHC class I-related (MIC) molecules, however, are stress-induced
      by ill-defined stimuli. Two families of ligands for the human activating NKG2D
      receptor have been identified. These are the MIC proteins encoded by two highly
      polymorphic genes within the MHC class I and the retinoic acid-inducible early
      gene-1-like (also designated UL16-binding) proteins encoded by genes outside the
      MHC. For the mouse NKG2D receptor, one family, containing at least five distinct
      ligands, has been described. A better understanding about how targets signal
      their distress, which renders them susceptible to natural killer (NK)-cell
      attack, will help to define the role of NK cells in antimicrobial and antitumor
      immunity and transplantation.

PMID- 11513138
TI  - Strategies for target cell recognition by natural killer cells.
AB  - Stimulation of natural killer (NK) cells is regulated by a complex balance of
      inhibitory and stimulatory receptors expressed by NK cells. However, the
      interaction of stimulatory receptors and their ligands is poorly understood. One
      stimulatory receptor, NKG2D, is expressed by all NK cells, stimulated CD8+ T
      cells, gammadelta T cells and macrophages. Recently, progress has been made in
      defining cellular ligands for NKG2D. Four different families of ligands have been
      identified in mice and humans, all of which are distantly related to MHC class I
      molecules. Some of the ligands are upregulated in transformed and infected cells,
      provoking an attack by the innate and adaptive immune systems. It appears that
      these "induced-self" ligands recognized by the NKG2D receptor may be a precedent
      for a new strategy of target cell recognition by the immune system.

PMID- 11513139
TI  - The UL16-binding proteins, a novel family of MHC class I-related ligands for
      NKG2D, activate natural killer cell functions.
AB  - The UL16-binding proteins (ULBPs) are a novel family of MHC class I-related
      molecules (MICs) that were identified based on their ability to bind to the human
      cytomegalovirus (HCMV) glycoprotein UL16. UL16 also binds to a member of another
      family of MHC class I-like molecules, MICB. The ULBPs and MICs are ligands for
      NKG2D/DAP10, an activating receptor expressed by natural killer (NK) cells and
      other immune effector cells, and this interaction can be blocked by UL16.
      Engagement of NKG2D/DAP10 by ULBPs or MICs expressed on a target cell can
      overcome an inhibitory signal generated by NK-cell recognition of MHC class I
      molecules and trigger NK cytotoxicity. ULBPs elicit their effects on NK cells by
      activating the janus kinase 2, signal transducer and activator of transcription
      5, extracellular-signal-regulated kinase mitogen-activated protein kinase and
      Akt/protein kinase B signal transduction pathways. Although ULBPs alone activate
      multiple signaling pathways and induce modest cytokine production, ULBPs
      synergize strongly with interleukin-12 for production of interferon-gamma by NK
      cells. This finding is consistent with reports in T cells that NKG2D/DAP10 can
      act as a co-stimulatory receptor in a similar manner as CD28. The possible roles
      of ULBPs in mediating immune responses to viruses and tumors and the potential
      mechanisms by which UL16 may allow HCMV to evade immune detection are areas of
      active investigation.

PMID- 11513140
TI  - Human cytomegalovirus and natural killer-mediated surveillance of HLA class I
      expression: a paradigm of host-pathogen adaptation.
AB  - Among various strategies to evade the host immune response, some viruses like
      human cytomegalovirus (HCMV) interfere with surface MHC class I expression and
      antigen presentation to T lymphocytes. The ability of natural killer (NK) cells
      to detect MHC class I molecules through inhibitory receptors can be envisaged as
      an adaptation of the immune system for responding to such pathological
      alterations. To fulfil that role, rodents use members of the Ly49 C-type lectin
      superfamily, whereas primates employ killer immunoglobulin-like receptors and the
      immunoglobulin-like transcript 2/leucocyte immunoglobulin-like receptor-1
      receptor. CD94/NKG2 lectin-like heterodimers represent the most conserved
      receptor system for MHC class I molecules; by interacting with human HLA-E or
      murine Qa-1b, CD94/NKG2A inhibitory receptors broadly probe the biosynthesis
      pathway of other class I molecules. Reciprocally, HCMV has developed mechanisms
      to evade the NK response while modulating HLA class Ia expression. The ability of
      HCMV to maintain surface levels of HLA-E and to express an HLA class I surrogate
      (UL18) are herein discussed in the context of the interplay with human NKR
      systems.

PMID- 11513141
TI  - The genomic context of natural killer receptor extended gene families.
AB  - The two sets of inhibitory and activating natural killer (NK) receptor genes
      belong either to the Ig or to the C-type lectin superfamilies. Both are extensive
      and diverse, comprising genes of varying degrees of relatedness, indicative of a
      process of iterative duplication. We have constructed gene maps to help
      understand how and when NK receptor genes developed and the nature of their
      polymorphism. A cluster of over 15 C-type lectin genes, the natural killer
      complex is located on human chromosome 12p13.1, syntenic with a region in mouse
      that borders multiple Ly49 loci. The equivalent locus in man is occupied by a
      single pseudogene, LY49L. The immunoglobulin superfamily of loci, the leukocyte
      receptor complex (LRC), on chromosome 19q13.4, contains many polymorphic killer
      cell immunoglobulin-like receptor (KIR) genes as well as multiple related
      sequences. These include immunoglobulin-like transcript (ILT) (or leukocyte
      immunoglobulin-like receptor genes), leukocyte-associated inhibitory receptor
      genes (LAIR), NKp46, Fc alphaR and the platelet glycoprotein receptor VI locus,
      which encodes a collagen-binding molecule. KIRs are expressed mostly on NK cells
      and some T cells. The other LRC loci are more widely expressed. Further
      centromeric of the LRC are sets of additional loci with weak sequence similarity
      to the KIRs, including the extensive CD66(CEA) and Siglec families. The LRC
      syntenic region in mice contains no orthologues of KIRs. Some of the KIR genes
      are highly polymorphic in terms of sequence as well as for presence/absence of
      genes on different haplotypes. Some anchor loci, such as KIR2DL4, are present on
      most haplotypes. A few ILT loci, such as ILT5 and ILT8, are polymorphic, but only
      ILT6 exhibits presence/absence variation. This knowledge of the genomic
      organisation of the extensive NK superfamilies underpins efforts to understand
      the functions of the encoded NK receptor molecules. It leads to the conclusion
      that the functional homology of human KIR and mouse Ly49 genes arose by
      convergent evolution. NK receptor immunogenetics has interesting parallels with
      the major histocompatibility complex (MHC) in which some of the polymorphic genes
      are ligands for NK molecules. There are hints of an ancient genetic relationship
      between NK receptor genes and MHC-paralogous regions on chromosomes 1, 9 and 19.
      The picture that emerges from both complexes is of eternal evolutionary
      restlessness, presumably in response to resistance to disease.

PMID- 11513142
TI  - Human natural killer cell receptors and co-receptors.
AB  - In the absence of sufficient signaling by their HLA class I-specific inhibitory
      receptors, human natural killer (NK) cells become activated and display potent
      cytotoxicity against cells that are either HLA class I negative or deficient.
      This indicates that the NK receptors responsible for the induction of
      cytotoxicity recognize ligands on target cells different from HLA class I
      molecules. On this basis, the process of NK-cell triggering can be considered as
      a mainly non-MHC-restricted mechanism. The recent identification of a group of NK
      specific triggering surface molecules has allowed a first series of pioneering
      studies on the functional/molecular characteristics of such receptors. The first
      three members of a receptor family that has been termed natural cytotoxicity
      receptors (NCR) are represented by NKp46, NKp44 and NKp30. These receptors are
      strictly confined to NK cells, and their engagement induces a strong activation
      of NK-mediated cytolysis. A direct correlation exists between the surface density
      of NCR and the ability of NK cells to kill various target cells. Importantly, mAb
      mediated blocking of these receptors has been shown to suppress cytotoxicity
      against most NK-susceptible target cells. However, the process of NK-cell
      triggering during target cell lysis may also depend on the concerted action of
      NCR and other triggering receptors, such as NKG2D, or surface molecules,
      including 2B4 and NKp80, that appear to function as co-receptors rather than as
      true receptors. Notably, a dysfunction of 2B4 has been associated with a severe
      form of immunodeficiency termed X-linked lymphoproliferative disease. Future
      studies will clarify whether also the altered expression and/or function of other
      NK-triggering molecules may represent a possible cause of immunological
      disorders.

PMID- 11513143
TI  - Activating and inhibitory nature of the murine paired immunoglobulin-like
      receptor family.
AB  - Clones for murine paired immunoglobulin-like receptors (PIR) were first isolated
      as those coding for type I transmembrane glycoproteins with six immunoglobulin
      like domains homologous to human Fc alphaR, bovine Fc gamma2R, and other related
      receptors. However, they turned out to bind neither IgA nor other immunoglobulins
      in the case of the ectopic expression on COS-1 fibroblastic cells. PIR-A and B
      are expressed on a wide variety of cells in the murine immune system, such as in
      B cells, mast cells, macrophages, and dendritic cells, mostly in a pairwise
      fashion. PIR-A requires homodimeric Fc receptor common gamma chain, which harbors
      an immunoreceptor tyrosine-based activation motif, for its efficient cell surface
      expression and for the delivery of activation signaling. In contrast, PIR-B
      contains immunoreceptor tyrosine-based inhibitory motifs (ITIMs) in its
      cytoplasmic portion and inhibits receptor-mediated activation signaling in vitro
      upon engagement with other activating-type receptors such as the antigen receptor
      on B cells and the high affinity Fc receptor for IgE on mast cells. ITIMs of PIR
      B on macrophages and B cells have been shown to be constitutively phosphorylated
      in their tyrosine residues. Although the ligand for PIR still remains unknown,
      the transgenics and the gene-targeted mice will provide us with valuable
      information on their physiological roles in the immune regulation.

PMID- 11513144
TI  - Inhibition of natural killer cell activation signals by killer cell
      immunoglobulin-like receptors (CD158).
AB  - The killer cell immunoglobulin-like receptor (KIR) family includes receptors that
      bind to HLA class I molecules on target cells and inhibit natural killer (NK)
      cell cytotoxicity, and receptors such as KIR3DL7 with no known ligand and
      function. Inhibitory KIR recruit the tyrosine phosphatase SHP-1 to block signals
      transduced by any one of a number of activation receptors. Inhibition of overall
      protein tyrosine phosphorylation by SHP-1 during binding of KIR to MHC class I on
      target cells is selective, suggesting that a limited number of substrates are
      dephosphorylated by SHP-1. We have chosen to study KIR inhibition as it occurs
      during binding of KIR to MHC class I on target cells, despite the technical
      limitations inherent to studies of processes regulated by cell contact. KIR
      binding to MHC class I on target cells inhibits tyrosine phosphorylation of the
      activation receptor 2B4 (CD244) and disrupts adhesion of NK cells to target
      cells. Inhibition of proximal events in NK activation may increase the
      availability of NK cells by liberating them from non-productive interactions with
      resistant target cells. As the receptors and the signaling pathways that induce
      NK cytotoxicity are not fully characterized, elucidation of the inhibitory
      mechanism employed by KIR may provide insight into NK activation.

PMID- 11513145
TI  - 2B4 (CD244) and CS1: novel members of the CD2 subset of the immunoglobulin
      superfamily molecules expressed on natural killer cells and other leukocytes.
AB  - 2B4 is a member of the CD2 subset of the immunoglobulin superfamily molecules
      expressed on natural killer (NK) cells and other leukocytes. It is the high
      affinity ligand for CD48. Engagement of 2B4 on NK-cell surfaces with specific
      antibodies or CD48 can trigger cell-mediated cytotoxicity, interferon-gamma
      secretion, phosphoinositol turnover and NK-cell invasiveness. The function of 2B4
      in CD8+ T cells and myeloid cells remains unknown. The cytoplasmic domain of 2B4
      contains unique tyrosine motifs (TxYxxV/I) that associate with src homology 2
      domain-containing protein or signaling lymphocyte activation molecule (SLAM)
      associated protein, whose mutation is the underlying genetic defect in the X
      linked lymphoproliferative disease (XLPD). Impaired signaling via 2B4 and SLAM is
      implicated in the immunopathogenesis of XLPD. CS1 is a novel member of the CD2
      subset that contains two of the unique tyrosine motifs present in 2B4 and SLAM.
      Signaling through 2B4, CS1 and other members of the CD2 subset may play a major
      role in the regulation of NK cells and other leukocyte functions.

PMID- 11513146
TI  - Novel immune-type receptor genes.
AB  - Novel immune-type receptor (NITR) genes, which initially were identified in the
      Southern pufferfish (Spheroides nephelus), encode products which consist of an
      extracellular variable (V) and V-like C2 (V/C2) domain, a transmembrane region,
      and a cytoplasmic tail, which typically possesses an immunoreceptor tyrosine
      based inhibition motif (ITIM). Multiple NITR genes have been identified in close,
      contiguous chromosomal linkage. The V regions of NITRs resemble prototypic forms
      defined for immunoglobulin (Ig) and T-cell antigen receptor (TCR), are present in
      multiple families and exhibit regionalized variation in sequence, which also
      occurs in Ig and TCR. Comparisons of exons encoding transmembrane and cytoplasmic
      regions of multiple NITRs suggest that exon shuffling has factored in the
      diversification of the NITR gene complex. Zebrafish (Danio rerio) NITRs exhibit
      many of these characteristics. NITRs that have been identified in additional
      species of bony fish demonstrate additional variation in the number of
      extracellular domains as well as in the presence of intramembranous charged
      residues, cytoplasmic tails and ITIMs. The presence in NITRs of V regions that
      are related closely to those found in Ig and TCR, as well as regulatory motifs
      and other structural features that are characteristic of immune inhibitory
      receptors encoded at the leukocyte receptor cluster, suggests that the NITRs are
      representative of an integral stage in the evolution of innate and adaptive
      immune function.

PMID- 11513147
TI  - p75/AIRM1 and CD33, two sialoadhesin receptors that regulate the proliferation or
      the survival of normal and leukemic myeloid cells.
AB  - Inhibitory receptors originally identified in natural killer (NK) cells have also
      been detected in other leukocyte types, thus suggesting that they may play a more
      general role in the control of leukocyte function. Here we report data on
      p75/adhesion receptor molecule 1 (AIRM1), a surface inhibitory receptor of the
      sialoadhesin family originally identified in NK cells that is also expressed by
      normal and leukemic myeloid cells. Given the homology between p75/AIRM1 and CD33,
      we also reanalyzed CD33, a major myeloid marker of still unknown function. We
      discuss recent data indicating that engagement of p75/AIRM1 or CD33 sharply
      inhibits the in vitro proliferation/differentiation of CD34+ myeloid precursors
      induced by stem cell factor and granulocyte-macrophage colony-stimulating factor.
      Importantly, a similar in vitro inhibitory effect occurs in monocyte/macrophages
      as well as in chronic or acute myeloid leukemias. While CD33 appears to act via
      the induction of apoptosis, p75/AIRM1 blocks cell proliferation but does not
      appear to induce apoptosis. A synergistic effect in the induction of apoptosis
      has also been documented between antibodies specific for CD33 and the
      chemotherapic agent etoposide. Taken together, the use of appropriate ligands
      against CD33 or p75/AIRM1 may represent a new therapeutic tool for treatment of
      myeloid leukemias or diseases characterized by overwhelming macrophage
      activation.

PMID- 11513148
TI  - Biology of T memory type 1 cells.
AB  - Engagement of inhibitory natural killer (NK) cell receptors for MHC class I
      molecules (NKR) can impair NK-cell activation programs. Inhibitory NKR thus
      confer to NK cells the capacity to discriminate between MHC class I+ and MHC
      class I- target cells, and are therefore involved in the control of NK-cell
      tolerance to self, as well as in the elimination of MHC class I- distressed cells
      by NK cells. In human and mouse, a subset of alphabeta T cells also express
      inhibitory NKR at their surface, but the biological function of inhibitory NKR on
      T cells remains to be precisely elucidated. We refer to these cells as T memory
      type 1 (Tm1) cells, and review here the phenotypic and functional features of
      this subset of memory-phenotype CD8+ alphabeta T cells. In vitro studies suggest
      that inhibitory NKR are involved in the peripheral control of T-cell self
      tolerance. In vitro and in vivo analysis have revealed a novel biological
      function for inhibitory NKR when expressed on T cells. Indeed, engagement of
      inhibitory NKR on T cells provides them with survival signals against activation
      induced cell death. Thus, sensing of self-MHC class I molecules by inhibitory NKR
      displayed on alphabeta T cells leads to the in vivo accumulation of Tm1 cells.

PMID- 11513149
TI  - Immunobiology of natural killer cells and bone marrow transplantation: merging of
      basic and preclinical studies.
AB  - Natural killer (NK) cells mediate acute rejection of bone marrow, but not solid
      tissue, allografts in lethally irradiated mice. Precisely how and why this
      rejection occurs is still unclear. In allogeneic bone marrow transplantation
      (BMT), a spectrum of results is possible; one result can be marrow graft failure
      due to host rejection of the graft by NK and T cells and, at the opposite
      spectrum, the occurrence of graft-versus-host disease (GVHD). Donor NK cells,
      however, appear capable of improving donor engraftment without giving rise to
      GVHD and thus may be of use as an immunotherapy following BMT. As NK-cell
      inhibitory receptors play a role in bone marrow cell rejection, these same
      inhibitory receptors may also affect NK responses towards tumor cells. It has
      been demonstrated that blocking the interaction of inhibitory receptors with MHC
      determinants on tumor cells can result in greater antitumor effects. Thus, NK
      cells are capable of mediating both positive and negative effects during BMT
      depending on whether they are of host versus donor origin and their state of
      activation. Understanding their role in BMT provides insights as to their
      physiological roles and points the way to potential clinical uses.

PMID- 11513150
TI  - Genesis of the ILT/LIR/MIR clusters within the human leukocyte receptor complex.
AB  - The human leukocyte receptor complex (LRC) contains at least 26 genes which
      belong to the immunoglobulin superfamily The genes include two clusters of
      immunoglobulin-like transcript (ILT)/leukocyte immunoglobulin-like receptor
      (LIR)/monocyte-macrophage inhibitory receptor (MIR) loci, a cluster of killer
      cell inhibitory receptor (KIR) genes, two leukocyte-associated immunoglobulin
      like receptor genes, as well as the Fc receptor for IgA and the natural
      cytotoxicity receptor I loci. It has already been postulated that these genes
      have evolved by multiple duplications, while the two ILT clusters are likely to
      have been generated by the inverse duplication of an ancient ILT cluster. To shed
      more light on the possible origin of the loci within the LRC, we have now
      investigated the presence of KIR and ILT loci in a variety of vertebrates by
      hybridizations and compared the genomic sequences of all ILT genes. Our results
      lead to the following conclusions: 1) the origin of KIR genes dates back to about
      100 million years, but only primate and human KIRs are closely related; 2) in
      contrast, genes which are detectable with human ILT cDNAs are already found in
      birds, suggesting their presence already about 300 million years ago. Using the
      sequence data produced by the human genome project, we have developed a
      hypothesis that reconstructs the genesis of the two human ILT clusters in detail
      which will help to understand the function of the LRC.

PMID- 11513151
TI  - The centromeric part of the human natural killer (NK) receptor complex: lectin
      like receptor genes expressed in NK, dendritic and endothelial cells.
AB  - The human natural killer (NK) receptor complex encompasses a region of about 2 Mb
      on the short arm of chromosome 12. It contains at least 18 lectin-like receptor
      genes, of which some are expressed in NK and NK/T cells and function as NK
      receptors. Close to the CD94 and NKG2 NK receptor genes in the centromeric part,
      a novel family of genes, expressed in myeloid, dendritic and/or endothelial
      cells, recently became evident. These genes encode a receptor for oxidized low
      density lipoprotein in endothelial cells and three other receptors potentially
      serving regulatory functions in dendritic cells. Although the overall structure
      of the human NK receptor complex is similar to the syntenic rodent regions, the
      centromeric part lacks the cluster of Ly49 genes. This supports the notion that
      recognition of MHC class Ia molecules has evolved separately in rodents and
      humans in the lectin-like Ly49 and the killer immunoglobulin-like receptors,
      respectively. In the telomeric part, other lectin-like genes expressed in
      different hematopoietic lineages are found. The receptors of the NK receptor
      complex apparently serve important functions in several leukocytes and in
      endothelial cells, and the exact role of these receptors, their ligands, and
      their distinct and co-ordinate regulation in different cell lineages warrants
      further investigation.

PMID- 11513152
TI  - Structural basis of MHC class I recognition by natural killer cell receptors.
AB  - Natural killer (NK)-cell function is regulated by NK receptors that recognize MHC
      class I (MHC-I) molecules on target cells. Two structurally distinct families of
      NK receptors have been identified, the immunoglobulin-like family (killer cell
      immunoglobulin-like receptors (KIRs), leukocyte immunoglobulin-like receptors
      (LIRs)) and the C-type lectin-like family (Ly49, CD94/NKG2A, NKG2D, CD69).
      Recently, the three-dimensional structures of several NK receptors were
      determined, in free form or bound to MHC-I. These include those of unbound KIRs,
      NKG2D, CD69, LIR-1 and the CD94 subunit of the CD94/NKG2A heterodimer. Together,
      these structures define the basic molecular architecture of both the
      immunoglobulin-like and C-type lectin-like families of NK receptors. In addition,
      crystal structures have been reported for the complex between Ly49A and H-2Dd,
      and for KIR2DL2 bound to HLA-Cw3. The complex structures provide a framework for
      understanding MHC-I recognition by NK receptors from both families and reveal
      striking differences in the nature of this recognition, despite the receptors'
      functional similarity.

PMID- 11513153
TI  - Structure of killer cell immunoglobulin-like receptors and their recognition of
      the class I MHC molecules.
AB  - The recognition of class I MHC molecules by killer cell immunoglobulin-like
      receptors (KIR) constitutes an integral part of immune surveillance by the innate
      immune system. To understand the molecular basis of this recognition, the
      structures of several members of this superfamily have been determined. Despite
      their functional diversity, members of this superfamily share many conserved
      structural features. A central question is how these receptors recognize their
      ligands. The recent determination of the crystal structure of KIR2DL2 in complex
      with HLA-Cw3 has revealed the molecular mechanisms underpinning this interaction,
      which ultimately modulates the cytolytic activity of natural killer cells. While
      the recognition of MHC molecules by KIR is characterized by a number of unique
      features, some unexpected similarities with T-cell receptor recognition of MHC
      molecules are also observed. The detailed interactions between KIR2DL2 and HLA
      Cw3 and their functional implications will be reviewed here.

PMID- 11513154
TI  - The ever-expanding Ly49 gene family: repertoire and signaling.
AB  - The mouse lectin-related Ly49 family and the human killer cell Ig-like receptor
      (KIR) family represent structurally distinct, yet functionally analogous, class I
      MHC receptors that are expressed on natural killer cells and some T cells. The
      functional similarity of these two families has been borne out by the
      demonstration of identical signal transduction pathways associated with each
      receptor family. The Ly49 family therefore provides a useful model system to
      study the role of this dass of receptors in the regulation of the immune system.
      Recent data relating to the Ly49 repertoire in several mouse strains has revealed
      an additional evolutionary parallel between KIR and Ly49 receptor families. There
      is now an appreciation of the variation in the number and type of Ly49s expressed
      in different mouse strains, similar to the previously demonstrated differences in
      the number of KIR genes found in humans. This review summarizes the current
      members of the Ly49 gene family, their MHC class I recognition and associated
      signal transduction pathways.

PMID- 11513155
TI  - Ly49 and CD94/NKG2: developmentally regulated expression and evolution.
AB  - Murine natural killer (NK) cells express two families of MHC class I-specific
      receptors, namely the Ly49 family and CD94/NKG2 heterodimers. Stochastic co
      expression of these receptors generates diverse receptor repertoires in adult NK
      cell populations, whereas fetal NK cells have much more limited receptor
      diversity as they mostly express CD94/NKG2A but not Ly49. These receptors are
      also expressed on CD8-T cells and NK1.1+ T cells and regulate their functions,
      but their expression pattern on NK cells is significantly different from those on
      T cells. Thus, expression of Ly49 and CD94/NKG2 is developmentally regulated. NK
      cells acquire the Ly49 family of receptors in an orderly manner as they
      differentiate from bone marrow progenitors in vitro. Similarly, acquisition of
      CD94 and NKG2 by NK cells as they differentiate from embryonic stem cells is also
      orderly To gain insight into the mechanisms regulating Ly49 expression, potential
      regulatory regions of several Ly49 genes have been examined. Ly49 genes with
      different expression patterns have remarkably similar sequences in the putative
      regulatory regions. Finally, a functional Ly49 gene has been identified in
      baboon, and primate comparisons suggest that functional extinction of the Ly49
      gene in the human lineage seems to have been a relatively recent event.

PMID- 11513156
TI  - Clearance of the cervical spine in multitrauma patients: the role of advanced
      imaging.
AB  - The cervical spine is injured in 3% of major trauma patients. Radiographic
      clearance for injury must be provided efficiently and accurately. There are
      numerous choices for clearance that are now in clinical practice: lateral
      radiograph only, 3-view or 5-view cervical-spine (c-spine) series, flexion
      extension radiographs, computed tomography (CT) with multiplanar reformations,
      and magnetic resonance imaging (MRI). This article reviews the literature on
      methods of c-spine clearance, and emphasizes the pitfalls of each modality.
      Although lateral radiographs detect 60% to 80% of c-spine fractures, a
      significant number of fractures are not visible, even when three views of the
      spine are obtained. The sensitivity of plain radiographs can be improved by
      attention to several subtle features, which are discussed. Flexion-extension
      radiographs in the acute setting have an unacceptably high false-negative and
      false-positive rate. CT detects 97% to 100% of fractures, but its accuracy in
      detection of purely ligamentous injuries has not been documented. Furthermore, CT
      is limited in patients with severe degenerative disease. MRI is highly sensitive
      in the detection of ligamentous injury, but not all cases of injury may cause
      instability. MRI is also much less sensitive than CT to fractures of the
      posterior elements of the spine, and to injuries of the craniocervical junction.
      The causes of missed cervical spine injury and delayed instability are discussed
      and shown in this article. An algorithm for the use of advanced imaging is
      proposed.

PMID- 11513157
TI  - Radiographic imaging for treatment and follow-up of developmental dysplasia of
      the hip.
AB  - Developmental dysplasia of the hip (DDH) is a spectrum of abnormalities that can
      range from a very mild disturbance to a very severe process that is
      incapacitating later in life. This article considers the causative factors and
      natural history of DDH, as well as anatomic abnormalities, physical examination
      findings, and both surgical and nonsurgical treatment options. The goal of this
      article is to place in perspective the use of advanced imaging techniques in the
      diagnosis and follow-up of patients with DDH. Ultrasound, computed tomography
      (CT), and magnetic resonance (MR) findings are reviewed with respect to the
      diagnosis of DDH, treatment complications, and long-term problems that may occur
      in treated and untreated patients.

PMID- 11513158
TI  - Magnetic resonance imaging of autologous chondrocyte implantation.
AB  - There is now over 10 years experience with autologous chondrocyte implantation
      (ACI) for the management of full-thickness chondral injuries in the knee. This
      article briefly reviews the surgical procedure, the time lines of graft
      maturation, and patient rehabilitation in the context of postoperative magnetic
      resonance imaging (MRI) assessment. The normal and abnormal appearances of ACI
      repair cartilage on MR images are described, with an emphasis on the MR
      appearances of the complications that may occur after this procedure, and the
      usefulness of MR imaging for the surgeon.

PMID- 11513159
TI  - Osteochondral injuries.
AB  - Osteochondral injuries are an important type of musculoskeletal trauma that can
      lead to disabling arthritis if not recognized and treated appropriately in the
      early stages. The anatomic configuration and biomechanical function of a joint
      are important for understanding its particular pattern of osteochondral injury
      and the resultant imaging appearance. The imaging of osteochondral fractures and
      osteochondrosis dissecans (OCD) is reviewed in this article, with particular
      attention to differentiating surgical and nonsurgical lesions on the basis of
      their appearance with advanced imaging modalities. Computed tomography (CT) and
      magnetic resonance imaging (MRI) have improved both the sensitivity and
      specificity for detection and characterization of osteochondral injuries. MRI is
      currently the modality of choice for the detection and staging of osteochondral
      injuries. It has the greatest sensitivity owing to its ability to depict marrow
      edema and directly assess the fracture clefts of stage 3 lesions, as well as the
      morphology of articular cartilage. Newer strategies for differentiating stable
      from unstable osteochondral fragments include MR arthrography and intravenous
      contrast-enhanced MRI.

PMID- 11513160
TI  - MR imaging of patellar dislocation and relocation.
AB  - Patellar dislocation and relocation (PDR) typically occurs suddenly after trauma
      or torsional stress on the extensor mechanism. Clinical evaluation after patellar
      dislocation/relocation usually reveals a swollen knee that is difficult to
      examine. Radiographs may show hemathroses and a minority of patients will have a
      chip fracture of the patella. Magnetic resonance (MR) imaging features seen with
      PDR include disruption or sprain of the medial retinaculum, lateral patellar tilt
      or subluxation, lateral femoral condylar and medical patellar osseous contusions,
      osteochondral injury, damage to Hoffa's fat pad, and joint effusion. Up to one
      third of patients will also show concomitant injury to the major ligaments of the
      knee or menisci. Without repair of the primary injury, redislocation occurs in
      greater than one half of patients. Consequently, surgical correction is often
      advocated. This article reviews the factors predisposing to PDR, the activities
      associated with PDR, the clinical, radiographic, and MR imaging features of PDR,
      and (briefly) therapy for this injury.

PMID- 11513161
TI  - Shoulder MRI refinements: differentiation of rotator cuff tear from artifacts and
      tendonosis, and reassessment of normal findings.
AB  - One of the difficulties with rotator cuff imaging lies in the normal variability
      of the tendon's signal. There may be intermediate signal present within the
      tendon because of magic-angle phenomenon, muscle and tendon fiber
      interdigitation, or tendinopathy related to degenerative changes or overuse
      injury. Partial and complete rotator cuff tears should be distinguishable from
      these causes of intermediate signal if water signal is reliably identified. This
      article reviews the important issue of distinguishing between rotator cuff tear
      and other causes of high signal in the rotator cuff, including artifacts and
      tendonosis. We include a review of the literature and a brief report of a study
      we conducted on 20 shoulders of 14 asymptomatic, young volunteers. In this study,
      the rotator cuff tendons were evaluated for abnormal signal at different TE
      values to determine at what TE the interpreters were able to confidently
      distinguish the high-signal intensity of a tear (water) from the intermediate
      signal intensity associated with artifact and tendinopathy. Readers were able to
      distinguish water and tendon signal in 70% to 100% of fast-spin echo (FSE) fat
      saturated images with TE of 66, but there was interobserver variability at this
      TE, suggesting that it is less reliable than 88 ms in the identification of
      rotator cuff tears. By using FSE fat-saturated sequences with TE of 88 and fast
      spin echo inversion recovery (FSEIR) sequences, readers at all levels of
      experience were able to differentiate water signal intensity from tendon signal
      intensity in 100% of cases. Therefore, we suggest that either FSEIR images or FSE
      fat-saturated images with TE greater than 66 be used to facilitate the
      differentiation of fluid signal from intermediate increased signal intensity in
      rotator cuff imaging. Additionally, this article reviews the normal findings of
      shoulder magnetic resonance imaging (MRI) as revealed by the asymptomatic
      subjects included in our study, and assesses these findings in respect to
      previous publications. The normal features reviewed include the subacromion
      subdeltoid (SA/SD) bursa, the biceps tendon sheath, the acromioclavicular (AC)
      joint, and the greater tuberosity of the humerus. A small amount of fluid was
      commonly seen in the SA/SD bursa, as well as the biceps tendon sheath. Subjective
      down-sloping of the acromion in the coronal plane, mild degenerative change of
      the AC joint, and undersurface spurring of the AC joint were uncommon in our
      normal subjects. Cystic change limited to the posterior aspect of the greater
      tuberosity was identified in 15% to 45% of shoulders.

PMID- 11513162
TI  - Licorice for hepatitis C: yum-yum or just ho-hum?

PMID- 11513163
TI  - Hepatitis C: does race really matter?

PMID- 11513164
TI  - Infliximab therapy for ulcerative colitis: many unanswered questions.

PMID- 11513165
TI  - Anemia in patients with chronic inflammatory bowel disease.

PMID- 11513166
TI  - Barrett's-related esophageal adenocarcinoma: is chemoprevention a potential
      option?
AB  - OBJECTIVE: Review the rationale behind secondary prevention of Barrett's related
      esophageal adenocarcinoma and critically appraise the emerging literature
      regarding prevention of neoplasia in Barrett's esophagus with antisecretory
      and/or cyclo-oxygenase inhibition therapy. METHODS: The existing English language
      literature regarding secondary cancer prevention in patients with Barrett's
      esophagus is reviewed and its potential clinical implications discussed. RESULTS:
      There is biologic plausibility to pursue "chemoprevention" trials with
      antisecretory and/or cyclo-oxygenase inhibition therapy in patients with
      Barrett's esophagus. CONCLUSION: Chemoprevention trials using potent
      antisecretory therapy coupled with cyclo-oxygenase 2 inhibition are warranted and
      may provide a means of decreasing the occurrence of cancer and cancer-related
      mortality in this disease.

PMID- 11513167
TI  - Inconsistent association of esophageal symptoms, psychometric abnormalities and
      dysmotility.
AB  - OBJECTIVES: The aim of this study was to characterize the psychometric profiles
      of symptomatic patients with abnormal esophageal motility and symptomatic
      patients with normal manometric findings compared to asymptomatic controls.
      METHODS: A total of 113 patients with abnormal esophageal motility (7 achalasia,
      8 diffuse esophageal spasm, 27 nutcracker esophagus, 37 hypertensive lower
      esophageal sphincter, 21 hypotensive peristalsis, 13 failed peristalsis), 23
      symptomatic controls with similar esophageal symptoms but normal manometry, and
      27 asymptomatic controls were enrolled. Validated questionnaires assessing
      depression (Beck Depression Inventory), anxiety (Spielberger State Anxiety
      Inventory or Trait Anxiety Inventory), and somatization (Psychosomatic Symptom
      Checklist) were administered to all subjects. RESULTS: Patients with both
      esophageal symptoms and either hypertensive lower esophageal sphincter,
      nutcracker esophagus, or hypotensive contractions exhibited increased
      somatization, acute anxiety, or depression compared to asymptomatic controls but
      not compared to symptomatic controls. On the other hand, the psychometric
      profiles of patients with achalasia and diffuse esophageal spasm were strikingly
      normal. Among esophageal symptoms, chest pain was closely correlated with
      psychometric abnormalities. CONCLUSIONS: The esophageal symptoms of patients with
      abnormal esophageal motility may relate to the underlying psychological
      abnormalities, independent of manometric abnormalities.

PMID- 11513168
TI  - Provocation of transient lower esophageal sphincter relaxations by gastric
      distension with air.
AB  - OBJECTIVES: Transient lower esophageal sphincter relaxations (TLESRs) are the
      major mechanism permitting not only gastroesophageal reflux but also venting of
      air from the stomach. Triggering of TLESRs is provoked by gastric distension.
      Antireflux surgery is associated with impaired ability to belch. It is not known
      whether a reduced capacity to belch results from postoperative reduction in
      TLESRs. METHODS: We studied the occurrence of TLESRs, common cavities (indicator
      for gas gastroesophageal reflux), and belching after standardized acute gastric
      distension by air insufflation (750 ml). Control subjects (n = 10), patients with
      gastroesophageal reflux disease (GERD) (n = 22), and patients after
      fundoplication (n = 24) were studied. LES and esophageal motilities were recorded
      with perfusion manometry. RESULTS: Gastric distension with air significantly (p <
      0.05) increased TLESR frequency in controls (1.6+/-0.3 to 3.5+/-1.0 per 20 min),
      GERD patients (1.2+/-0.3 to 3.1+/-0.5 per 20 min), and patients after
      fundoplication (0.5+/-0.1 to 1.8+/-0.6 per 20 min). Postfundoplication the number
      of TLESRs was significantly reduced (p < 0.05) both under fasting conditions and
      after air insufflation. The number of common cavities and belches after gastric
      air distension also was significantly reduced (p < 0.05) after fundoplication:
      2.3+/-0.6 versus 4.7+/-0.4 in controls and 4.1+/-0.4 in GERD patients. About half
      of the common cavities occurred during TLESRs, and half during other mechanisms.
      An impaired ability to belch in daily life correlated with an impaired belching
      response during the test. An impaired ability to belch occurred only in patients
      with complete fundoplication and not in patients with partial fundoplication and
      was associated with a reduced number of common cavities after gastric air
      insufflation. CONCLUSIONS: Short-lasting gastric air distension 1) provokes
      TLESRs but does not differentiate GERD patients from controls, 2) reveals
      impaired belching capacity in patients after complete fundoplication, and 3)
      shows that common cavities do not exclusively occur during TLESRs.

PMID- 11513169
TI  - Helicobacter pylori and gastric lymphoma: high seroprevalence of CagA in diffuse
      large B-cell lymphoma but not in low-grade lymphoma of mucosa-associated lymphoid
      tissue type.
AB  - OBJECTIVE: Gastric lymphoma of mucosa-associated lymphoid tissue (MALT) type is
      closely related to Helicobacter pylori (H. pylori) infection. In vitro studies
      have demonstrated H. pylori-induced B cell proliferation to be strain dependent.
      High prevalences of CagA protein and FldA protein have been reported in strains
      obtained from patients with gastric lymphoma of MALT type. The aims of the
      present study were to evaluate the prevalence of H. pylori infection and to
      search for antigenic particularities in 53 patients with primary gastric lymphoma
      in comparison with a group of infected patients with benign disease. METHODS: Of
      the 53 patients, 37 presented with low-grade lymphoma of MALT type (LGLM) and 16
      with diffuse large B-cell lymphoma (DLBCL). They were compared to a group of 162
      H. pylori-infected subjects comprising the control group: 111 had gastric or
      duodenal ulcer (GDU) and 51 nonulcer dyspepsia (NUD). Diagnosis of gastric
      lymphoma was established on histological examination of endoscopic specimens.
      Anti-H. pylori antibodies were assayed by third-generation ELISA. Western blot
      assay was used to detect antibodies against nine antigens (including CagA
      protein), which were recognized on the basis of their molecular weight. RESULTS:
      Of the 53 patients with gastric lymphoma, 45 were H. pylori-positive (85%): of
      these, 25 (56.5%) had anti-CagA antibodies. The prevalence of H. pylori
      seropositivity was 78% (29/37) in LGLM and 100% (16/16) in DLBCL. The prevalence
      of CagA seropositivity in H. pylori-positive patients was 44.8% (13/29) and 75%
      (12/16), respectively (p < 0.05). In comparison, the seroprevalence of CagA was
      77.4% (86/111) in GDU patients and 43.1% (22/53) in NUD patients. The prevalence
      of antibodies to other antigenic proteins detected with Helicoblot 2.0 (19.5kd,
      30kd, 35kd, VacA, HSPb, Urease A, and Urease B) did not differ among the groups
      except for 35kd protein, which was significantly higher (p < 0.01) in GDU than in
      NUD and in LGLM (76.6% vs 49% and 46.7%). CONCLUSION: These findings suggest that
      in patients who develop gastric lymphomas in response to H. pylori, virulent
      strains expressing CagA protein are preferentially associated with DLBCL.

PMID- 11513170
TI  - Helicobacter pylori eradication treatment does not benefit patients with nonulcer
      dyspepsia.
AB  - OBJECTIVES: The aim of this study was to assess the still controversial role of
      treatment of Helicobacter pylori (H. pylori) infection in patients with nonulcer
      dyspepsia. METHODS: We conducted a double-blind, randomized, placebo-controlled,
      multicenter trial comparing the efficacy of 7 days of eradication treatment
      (lansoprazole 15 mg b.i.d., amoxicillin I g b.i.d., and clarithromycin 500 mg
      b.i.d.) with a control treatment (lansoprazole 15 mg b.i.d. and placebo) in H.
      pylori-infected patients with nonulcer dyspepsia. 13C breath tests were performed
      at baseline and during follow-up. We assessed patient symptoms, health status
      (based on the SF-12 questionnaire), patient satisfaction, drug consumption,
      health care consultation behavior, and absenteeism related to dyspepsia over a 1
      yr period. RESULTS: A total of 74 patients randomized to eradication treatment
      and 70 patients randomized to placebo were compared. The rate of eradication of
      H. pylori infection was 75% in the active treatment group and 4% in the placebo
      group (p < 0.005). The symptom score improved to a similar extent in the group
      receiving active treatment (-4.0; 95% CI = -5.0 to -3.0) and placebo (-3.6; 95%
      CI = -4.5 to -2.7). Treatment response was not related to the severity or
      duration of initial symptoms or to the severity of gastritis on histology.
      Quality of life scores were comparable at 12 months. There was no significant
      difference in dyspepsia-related absenteeism or satisfaction with management of
      NUD. Patients receiving active treatment were more likely not to have had to use
      any dyspepsia treatment over the 12 months (60.8% vs 44.3%; p = 0.047).
      CONCLUSIONS: This study did not demonstrate any substantial benefit of curing H.
      pylori infection in patients with nonulcer dyspepsia. The study adds further
      evidence that H. pylori is not the main pathogenetic or therapeutic target in
      these patients.

PMID- 11513171
TI  - Gastric cardia inflammation: role of Helicobacter pylori infection and symptoms
      of gastroesophageal reflux disease.
AB  - OBJECTIVE: Although high prevalences of both chronic inflammation (carditis) and
      intestinal metaplasia at the gastric cardia have been reported, the pathogenesis
      is still unclear. This study assesses the role of Helicobacter pylori (H. pylori)
      infection and symptoms of gastroesophageal reflux disease (GERD) in these
      histological alterations. METHODS: Consecutive patients who underwent upper
      endoscopy were enrolled in the study, irrespective of their symptoms. Patients
      previously treated for H. pylori infection and those using proton pump inhibitors
      were excluded. Two biopsies were performed in the antrum, two in the gastric
      body, and two at the gastric cardia. All biopsies were used to look for H. pylori
      and for histological assessment. RESULTS: A total of 133 patients were enrolled.
      Carditis and intestinal metaplasia at the cardia were detected in 100 (75.2%) and
      in 18 (13.5%) patients, respectively. The H. pylori infection rate was
      significantly higher in patients with carditis than in those without it (87/100
      vs 7/33; p < 0.0001), and was higher in those with intestinal metaplasia at the
      cardia than in those without it (17/94 vs 1/39; p = 0.03). Conversely, the
      prevalence of GERD symptoms was not significantly different between patients with
      and without carditis (34/100 vs 16/33; p = NS), and between those with and
      without intestinal metaplasia (5/50 vs 13/83; p = NS). Interestingly, the
      prevalence of both H. pylori (64/94 vs 39/94; p = 0.0005) and intestinal
      metaplasia (18/133 vs 4/133; p = 0.0042) in the gastric cardia was significantly
      higher than that in gastric body. CONCLUSION: According to our study data, the
      gastric cardia is frequently infected with H. pylori with consequent development
      of both carditis and intestinal metaplasia, whereas GERD does not seem to be
      involved in these histological changes.

PMID- 11513172
TI  - Outpatient management of upper digestive hemorrhage not associated with portal
      hypertension: a large prospective cohort.
AB  - OBJECTIVES: To evaluate the safety of outpatient management of upper GI
      hemorrhage (UGIH) not associated with portal hypertension. METHODS: A prospective
      cohort of 983 subjects who went to the Accident & Emergency Department (A&ED) of
      a University hospital in Valencia (Spain), for UGIH not associated with portal
      hypertension during 1994 to 1997 were evaluated. After evaluation in the A&ED,
      216 patients (22%) were discharged and referred for outpatient follow-up, but 15
      patients could not be located thus, reducing the follow-up to 201 subjects. The
      main outcome measures were rebleeding within 10 days, emergency surgery within 15
      days, and mortality for any cause during the 30 days after the initial
      hemorrhaging episode. RESULTS: UGIH in subjects under outpatient care were less
      severe than those subjects in the hospitalized group. Hemorrhaging recurred in
      7.3% of inpatients versus 0.5% of outpatients (p < 0.01); emergency surgery was
      required in 5.6% of the hospitalized patients and 0.5% of the outpatients (p <
      0.01); a total of 20 deaths occurred in the hospitalized group (2.6%), while
      three (1.5%) occurred in outpatients (p = 0.26). After adjusting for several
      significant risk factors, outpatient management was not associated with outcomes
      that were worse. CONCLUSIONS: Treatment under an outpatient regime is a safe
      alternative for a large percentage of selected patients with UGIH not associated
      with portal hypertension.

PMID- 11513173
TI  - A survey on percutaneous endoscopically placed gastrostomy in the Northwest:
      influence of work setting.
AB  - OBJECTIVE: A survey was undertaken to determine the influence of practice setting
      on the way Pacific Northwest gastroenterologists perform and manage percutaneous
      endoscopically placed gastrostomy (PEG). METHODS: A 12-question survey was
      distributed to 196 members of the Pacific Northwest Gastroenterology Society
      (PNWGS) regarding their specifics of placing and managing PEG. The responses were
      compared according to work setting, i.e., private practice, armed services, staff
      model HMO's, and university affiliated hospitals. The data were analyzed using
      the chi2 test. RESULTS: Sixty-nine of 126 practicing gastroenterologists
      responded; 75% were in private practice (PP) and 25% in the combined other work
      settings (non-PP). The mean number of PEG placed by all groups was 23. Seventy
      three percent of PP performed PEG without a second physician. Antibiotics were
      used prophylactically in both PP and non-PP by 96%. There was no difference
      between groups in use of standardized forms or in time before instituting
      feedings. The non-PP groups used preprocedure labs (p = 0.037) and loosening skin
      surface bumpers (p = 0.035) more frequently. The uniform impression was that PEG
      was associated with the same or fewer complications currently than in the past.
      CONCLUSIONS: In the PP setting, gastroenterologists tend to place PEGs without a
      second physician and use standardized forms and bumper loosening less frequently
      than non-PP gastroenterologists. These variations reflect that teaching
      institutions as well as staff model HMOs make access to an assistant easier.
      Respondents expressed confusions on billing for PEG. They perceived the procedure
      to be as safe or safer than in the past. The PEG has evolved into a frequently
      performed procedure whose practice variations are outgrowths of one's work
      environment as well as one's training.

PMID- 11513174
TI  - Value of magnetic resonance cholangiography in the preoperative diagnosis of
      common bile duct stones.
AB  - OBJECTIVE: The aim of this study was to assess the performance of magnetic
      resonance cholangiography (MRC) in the preoperative diagnosis of
      choledocholithiasis. METHODS: A total of 147 consecutive patients underwent MRC
      for clinical and biological signs of common bile duct stones. ERCP was then
      carried out in 101 patients in whom there was a past history of cholecystectomy.
      The remaining 46 patients without a past history of biliary surgery underwent
      cholecystectomy and intraoperative cholangiography (IOC). The diagnosis obtained
      by MRC was compared with the final diagnosis established after endoscopic or
      surgical removal of calculi. RESULTS: A total of 113 patients had
      choledocholithiasis (single or multiple, including 15 cases of microlithiasis).
      There were no false-positive results with MRC. The false-negative results were
      caused mainly by small stones <3 mm in diameter, and to a lesser extent,
      cholangitis. Overall, the sensitivity was 93% and the specificity 100% for MRC in
      detecting common bile duct stones. The sensitivity and specificity of ERCP were
      respectively 94% and 100%, versus 93.5% and 93.3% for IOC. There was no
      statistically significant difference, however, between MRC and the other
      techniques. CONCLUSION: MRC is a key technique in the preoperative diagnosis of
      choledocholithiasis. Its diagnostic value is comparable to ERCP, but it appears
      to be more specific than IOC. Nevertheless, its diagnostic capability remains
      limited in cases of microlithiasis and cholangitis.

PMID- 11513175
TI  - Low molecular weight heparin versus unfractionated heparin in the colonoscopy
      peri-procedure period: a cost modeling study.
AB  - OBJECTIVE: The aim of this study was to compare the economic outcomes of peri
      procedure anticoagulation approaches for elective colonoscopy. METHODS: Decision
      analysis was used to model the economic outcomes of five peri-procedure
      anticoagulation options: outpatient low molecular weight heparin (LMWH),
      inpatient unfractionated heparin infusion (UFHi), continuous warfarin (with
      probability of a repeat procedure using LMWH or UFHi), and discontinuation of
      anticoagulation therapy. The model's base-case scenario assumed drug therapy
      options for high-risk patients were equally effective in preventing a
      thromboembolic event (0.1% risk), with a higher probability for the no
      anticoagulation strategy (0.4%); event costs were based on published data and
      adjusted to 1997 dollars. Drug costs reflected 1997 average wholesale price.
      Medical costs for other variables were estimated based on local hospital charges.
      Indirect costs were not considered. Risk probabilities and LMWH drug cost were
      tested in sensitivity analysis. RESULTS: In the base-case scenario, costs for the
      options evaluated were $1436/patient, $1792/patient, $1848/patient,
      $2629/patient, and $5196/patient for no anticoagulation, continuous
      warfarin/repeat LMWH, LMWH as outpatient, continuous warfarin/repeat UFHi, and
      UFHi as inpatient respectively ($1997). Discontinuing anticoagulation was the
      least costly approach but involved the greatest thromboembolic risk. The cost of
      continued warfarin anticoagulation/repeat LMWH was minimally less than the LMWH
      option, but assumes 25% of patients would require a second procedure. The
      traditional approach (UFHi) requires an extended hospitalization and is the most
      costly option. Varying risk category or LMWH cost in sensitivity analysis had a
      negligible impact on overall costs. CONCLUSION: Within the model's assumptions,
      LMWH offers a novel, convenient, and economical solution to the problem of peri
      procedure anticoagulation for elective colonoscopy.

PMID- 11513176
TI  - Endoscopic therapy of acute diverticular hemorrhage.
AB  - OBJECTIVE: Diverticular hemorrhage is a common cause of lower GI bleeding and can
      be diagnosed acutely during colonoscopy. However, whether early diagnosis leads
      to effective intervention remains controversial. The aim of this study was to
      evaluate whether urgent colonoscopic therapy is effective as acute and long term
      treatment for diverticular bleeding with stigmata of hemorrhage. METHODS: We
      reviewed the medical records of all patients who underwent endoscopic therapy for
      diverticular bleeding from January, 1994 to June, 2000 at Duke University Medical
      Center. Patients or their families were contacted to obtain complete follow-up
      including data on subsequent bleeding. RESULTS: We identified 13 patients who
      underwent colonoscopic hemostatic management for the treatment of acute
      diverticular bleeding. Therapy consisted of epinephrine injection and/or
      multipolar electrocoagulation. Five patients (38%) experienced early rebleeding,
      within 30 days of the index bleed, four of whom required surgery, and three
      patients (23%) had late rebleeding. There were no complications of endoscopic
      therapy. CONCLUSIONS: Endoscopic therapy can provide early hemostasis in some
      cases of acute diverticular hemorrhage. However, its value in preventing
      subsequent diverticular bleeding is unclear.

PMID- 11513177
TI  - Infliximab for refractory ulcerative colitis.
AB  - Eight patients with active ulcerative colitis (UC), refractory to usual
      combination medical therapy, were treated with a single i.v. dose of chimeric
      monoclonal antibody to recombinant human tumor necrosis factor alpha; many of
      these patients were scheduled for surgical colectomy because of their active
      disease. All patients responded extremely well to a single 5 mg/kg infusion of
      infliximab, with marked improvement after the infusion clinically,
      colonoscopically, and histologically on colonic biopsy. There were no significant
      complications or side effects; mean duration of remission has not been determined
      because none of the patients have relapsed. Infliximab appears to be a potent
      agent for inducing remission in refractory patients with ulcerative colitis.

PMID- 11513178
TI  - Prediction of response to iron sucrose in inflammatory bowel disease-associated
      anemia.
AB  - OBJECTIVE: Inflammatory bowel disease (IBD)-associated anemia responds to i.v.
      iron therapy. However, because of concurrent chronic inflammation, some patients
      do not respond adequately. Erythropoietin therapy has been shown to be effective
      in the latter cohort. Our goal was to find parameters that can predict the
      effectiveness of iron sucrose in IBD-associated anemia. METHODS: One hundred
      three patients with severe IBD-associated anemia (Hb < or = 10.5 g/dl) were
      treated prospectively for 4 wk with iron sucrose (total iron dose = 1.2 g) in an
      open label, multicenter trial. Treatment response was defined as an increase in
      Hb of > or =2.0 g/dl. A logistic regression analysis was performed with treatment
      response as the dependent variable and the following independent variables: serum
      erythropoietin, mean corpuscular Hb, transferrin, ferritin, soluble transferrin
      receptor (sTfR), C-reactive protein, interleukin 6 (IL-6), and disease activity.
      RESULTS: Sixty-seven of 103 patients (65%) responded to iron sucrose. From the
      variables under investigation, erythropoietin, sTfR, transferrin, and IL-6 were
      significantly associated with treatment response. The R2 values showed that
      erythropoietin (8.0%), sTfR (11.4%), and transferrin (10.4%), but not IL-6
      (1.3%), contribute a relevant amount of information to the model. An estimated
      80% probability of treatment response was found at erythropoietin levels of >166
      U/L, sTfR levels of >75 nmol/L, or transferrin levels of >3.83 g/L. CONCLUSIONS:
      Serum erythropoietin, sTfR, and transferrin concentrations have the potential to
      predict the response to iron sucrose therapy in IBD-associated anemia. These
      parameters may help to identify individuals who benefit the most from additional
      erythropoietin treatment.

PMID- 11513179
TI  - Cigarette smoking and celiac sprue: a case-control study.
AB  - OBJECTIVE: Environmental factors other than gliadin exposure and certain HLA
      haplotypes may play a role in the pathogenesis of celiac disease. Previous
      studies have suggested a strong inverse relationship between cigarette smoking
      and celiac disease. We sought to determine the relationship between celiac
      disease and cigarette smoking in our patient population. METHODS: All newly
      diagnosed adults with biopsy-proven celiac disease evaluated at Mayo Clinic
      Rochester between January 1, 1993, and June 30, 1998, were identified. Three
      clinic patients who were matched to each case on geographical area of residence,
      age, gender, and calendar year of visit served as controls. Smoking information
      was obtained from a standard medical questionnaire that was completed by all
      clinic patients at the time of registration. The adjusted odds ratio for celiac
      disease in current and former smokers relative to nonsmokers was estimated with a
      matched three-to-one conditional logistic regression model. RESULTS: A total of
      82 adults with biopsy-proven celiac disease were identified. At the time of
      diagnosis, the proportion of current smokers was 10% in cases and 10% in
      controls, yielding an adjusted odds ratio of 1.5 (95% CI = 0.5-4.3). In all, 34%
      of cases were former smokers versus 28% of controls, yielding an odds ratio of
      1.6 (95% CI = 0.8-3.2). CONCLUSION: This case-control study was unable to detect
      an association between cigarette smoking and celiac disease.

PMID- 11513180
TI  - Malignant melanoma: patterns of metastasis to the small bowel, reliability of
      imaging studies, and clinical relevance.
AB  - OBJECTIVES: The aims of this study were to determine the frequency of different
      patterns of melanoma metastases to small bowel on radiological examination, and
      to assess the reliability of the most commonly used radiological methods for
      detecting these lesions. METHODS: The records of cases archived as melanoma
      metastatic to the small bowel of the Armed Forces Institute of Pathology were
      reviewed. The clinical information, type of imaging procedure performed, and
      radiological features were analyzed and compared to the findings at surgery and
      at autopsy. RESULTS: A total of 32 patients had clinical and surgical data with
      pathological confirmation. Seven patients had metastasis involving the duodenum,
      22 had jejunal involvement, and 11 had ileal involvement. Metastases were
      categorized as polypoid, cavitary, infiltrating, or exoenteric. The polypoid
      pattern was seen in 20 patients (63%), six of whom showed multiple polypoid
      lesions (>10), referred to as polyposis. The "target lesion," a discrete polypoid
      mass with a central ulceration, was observed in only three (9%) of the 32
      patients. Eight patients (25%) demonstrated a cavitary pattern, a circumferential
      mass with inner marginal necrosis, and five (16%) showed an infiltrating pattern.
      One patient (3%) had an exoenteric lesion with a fistulous tract. The small bowel
      follow-through demonstrated 32 of 55 metastases (sensitivity 58%). Contrast
      enhanced CT demonstrated 32 of 48 masses (sensitivity 66%). Of the six cases of
      malignant polyposis, none were identified using CT, and only two were diagnosed
      by small bowel follow-through. CONCLUSIONS: The polypoid pattern, equally
      distributed between the jejunum and ileum, is the most common manifestation of
      metastatic melanoma to the small bowel. The target lesion was infrequently seen
      in this series. Small bowel follow-through and conventional CT seem to be
      unreliable in demonstrating melanoma metastases to the small bowel.

PMID- 11513181
TI  - A prospective cohort study of practice guidelines in inflammatory bowel disease.
AB  - OBJECTIVES: Practice guidelines should improve care, but they are not routinely
      followed, in part because of lack of proven benefit. We evaluated the effect of
      introducing guidelines for inflammatory bowel disease (IBD) on practice variation
      and the IBD Quality of Life (IBDQ) score. METHODS: This was a prospective,
      controlled, cohort study. A total of 65 patients were matched according to month
      of visit, diagnosis, and disease activity with control subjects seen 1 yr
      earlier. Physicians were educated throughout the study regarding the guidelines.
      Variation was measured by the Mayo Practice Guideline Score (MPGS), a 15-point
      assessment of documentation of diagnosis, nutrition, social support, education,
      functional status, and treatment. The IBDQ was measured at baseline and at 1 yr
      in the intervention group and after 1 yr in the control group. RESULTS: The MPGS
      was significantly higher in the intervention group compared to the controls (p =
      0.002), with median values of 12 versus 11. The IBDQ median score increased
      significantly in the intervention group (p < 0.001), baseline median of 133
      versus 15-month median of 184. However, the final IBDQ was not significantly
      higher in the intervention group than in the controls (p = 0.33). CONCLUSIONS:
      Practice guidelines for IBD reduce practice variation. The quality of life
      improved significantly compared to baseline with practice guidelines, but not
      compared to controls, perhaps because of the small sample size and homogenous
      practice setting. The MPGS is a tool that can be used in day-to-day management of
      IBD patients.

PMID- 11513182
TI  - Familial expression of anti-Saccharomyces cerevisiae Mannan antibodies in Crohn's
      disease and ulcerative colitis: a GISC study.
AB  - OBJECTIVES: Recent studies in familial Crohn's disease (CD) have suggested that
      anti-Saccharomyces cerevisiae mannan antibodies (ASCAs) may represent a new
      specific marker of genetic susceptibility. In this study we aimed to assess the
      importance of ASCAs by comparing their presence in a large number of patients
      with sporadic and familial occurrence of CD or ulcerative colitis (UC) and their
      unaffected relatives. METHODS: Serum samples from 96 patients with sporadic CD,
      97 patients with sporadic UC, and 50 unrelated healthy controls were tested for
      ASCAs by a standard ELISA method. Moreover, 73 families with two or more members
      affected by CD and/or UC were recruited. From these families 58 CD patients, 84
      UC patients, and 216 unaffected first degree relatives were investigated.
      RESULTS: ASCAs were detected in 34 of 96 patients with sporadic CD (35%, p < 0.01
      vs controls), 11 of 97 patients with sporadic UC (12%), and two of 50 controls
      (4%). ASCAs were significantly (p < 0.04) more frequent in patients with familial
      CD (55%) and familial UC (25%) than in sporadic cases. Moreover, ASCAs were found
      in 25% of unaffected relatives, and this rate did not significantly differ in CD,
      UC, and mixed families (28%, 26%, and 22%, respectively). CONCLUSIONS: In this
      study we confirm that ASCAs occur particularly frequently in CD patients,
      especially with the presence of a positive family history. However, they are also
      significantly increased in UC patients with a family history and in a
      considerable number of unaffected relatives of inflammatory bowel disease
      families, irrespective of the characteristics of their families (UC, CD, mixed,
      ASCA positive, and ASCA negative). The presence of ASCAs in unaffected relatives
      might point toward a genetic predisposition to either CD or UC.

PMID- 11513183
TI  - Alterations in cerebral potentials evoked by rectal distension in irritable bowel
      syndrome.
AB  - OBJECTIVE: Central nervous system correlates of the visceral hyperalgesia
      documented in patients with irritable bowel syndrome are limited. Reproducible
      cerebral evoked potentials can be recorded in response to rhythmic balloon
      distension of the rectum in healthy adults. Irritable bowel syndrome patients and
      healthy subjects were studied to compare the characteristics of mechanically
      evoked rectal cerebral potentials obtained during fasting and after the ingestion
      of a standard meal. METHODS: Twenty-two pairs of age-matched healthy female
      subjects and female irritable bowel syndrome patients were studied. Cerebral
      evoked potentials were recorded in response to rhythmic rectal distension (two
      distension series each of 100 repetitions at 0.8 hertz); cerebral evoked
      potential recordings were repeated after a 1000 kcal (46% fat) liquid meal. Trait
      and state anxiety questionnaires were also completed. RESULTS: Compared to
      healthy subjects, irritable bowel syndrome patients demonstrated higher
      prevalence of cerebral evoked potential early peaks (latency < 100 ms)
      postprandially, and uniformly shorter cerebral evoked potential latencies both
      before and after feeding. CONCLUSION: These findings provide further objective
      evidence for defective visceral afferent transmission in irritable bowel syndrome
      patients.

PMID- 11513184
TI  - Small intestinal motor patterns in critically ill patients after major abdominal
      surgery.
AB  - OBJECTIVES: In patients who have had major surgery or trauma, early enteral
      feeding is safer and more effective than parenteral or nasogastric feeding but is
      frequently associated with diarrhea. Limited recordings have shown that the
      patterning of duodenal interdigestive motor activity is frequently abnormal after
      surgery or in patients who are critically ill. The aims of this study were to
      evaluate the effects of major abdominal surgery on small intestinal motility, and
      to elucidate the motor patterns that occur postoperatively in critically ill
      patients in response to enteral feeding. METHODS: The effects of elective aortic
      aneurysm repair on small intestinal motility were studied in 11 patients aged 63
      77 yr. A 3.5-mm diameter multilumen extrusion was used to monitor pressures at 12
      points, distributed between the antrum and 100 cm distal to the pylorus. An
      additional lumen allowed enteral feeding into the duodenum. Recordings commenced
      immediately postoperatively and continued for up to 4 days. Data are given as
      means and SEMs. RESULTS: Bursts (frequency > 10/min) of small intestinal pressure
      waves that resembled phase III interdigestive motor activity occurred in all
      patients immediately after surgery. During mechanical ventilation, the timing of
      bursts along the segment evaluated was frequently abnormal for true
      interdigestive phase III activity, with simultaneous onset in multiple channels
      (46%), multiple or distal origins (8%), or retrograde migration (20%). When
      patients were not being ventilated, the migration pattern of the bursts was more
      typical of interdigestive phase III activity. The interval between bursts was
      unusually short for interdigestive motor activity, although it increased from
      30+/-12 min on day 1 to 41+/-18 min on day 3 (p < 0.05). A phase II pattern of
      pressure waves was virtually absent in all patients on all study days. In six
      patients who received postoperative enteral nutrition, the bursts of pressure
      waves were not abolished by feeding, contrary to normal phase III activity.
      CONCLUSIONS: Small intestinal pressure wave bursts are seen immediately after
      elective aortic aneurysm repair, but the migration of these bursts is frequently
      abnormal for phase III interdigestive activity. Duodenal nutrient delivery did
      not interrupt the occurrence of these bursts. Persistence of pressure wave bursts
      in this setting may be important in the delivery of enteral nutrition.

PMID- 11513185
TI  - Direct clinical evidence for spinal hyperalgesia in a patient with irritable
      bowel syndrome.
AB  - OBJECTIVE: Our objective was to evaluate GI motor and sensory function and spinal
      cord testing in a patient with severe irritable bowel syndrome. METHODS: A
      patient is described who underwent an extensive assessment of GI motor and
      sensory function including transit studies, colonic and rectal barostat studies,
      sensory and manometric studies of the small bowel, and colon and anorectal
      physiology testing. The patient also underwent testing with spinal cord
      stimulation and spinal drug delivery as part of a pain management assessment.
      RESULTS: The viscerosomatic referral pain pattern resulting from rectal
      distention was consistent with spinal hyperalgesia. The patient underwent testing
      for spinal cord stimulation and spinal drug delivery. CONCLUSION: This novel
      finding provides direct clinical evidence for the presence of spinal hyperalgesia
      in a patient with irritable bowel syndrome, consistent with the existing indirect
      clinical evidence and animal data.

PMID- 11513186
TI  - Glycyrrhizin-induced reduction of ALT in European patients with chronic hepatitis
      C.
AB  - OBJECTIVE: In Japan, ALT normalization induced by long-term i.v. glycyrrhizin
      treatment reportedly reduces the progression of liver disease to hepatocellular
      carcinoma in chronic hepatitis C patients. The aim of this study was to evaluate
      the short-term (4-wk) feasibility and efficacy on serum ALT of three or six times
      per week i.v. glycyrrhizin therapy in European patients. METHODS: Patients with
      chronic hepatitis C, nonresponders, or unlikely to respond (genotype 1/cirrhosis)
      to interferon therapy were included in this study. Medication was administered
      i.v. three or six times per week for 4 wk; follow-up also lasted 4 wk. RESULTS:
      Sixty-nine out of 72 treatment courses were completed according to protocol.
      There were no significant changes in ALT levels within the placebo group (n =
      13). The mean percentage ALT decrease from baseline at the end of treatment was
      26% and 47% for the three times per week and six times per week treatment group,
      respectively (both p < 0.001 vs placebo). At the end of active treatment, 10%
      (four of 41) and 20% (three of 15) of the patients reached normal ALT levels for
      the three times per week and six times per week treatment group, respectively.
      The ALT lowering effect disappeared after cessation of treatment. No major side
      effects were observed. CONCLUSION: It appeared feasible to treat European
      outpatients with chronic hepatitis C three or six times per week with i.v.
      glycyrrhizin. Glycyrrhizin treatment induces a significant ALT decrease in
      patients with chronic hepatitis C. Six times per week treatment appears more
      effective than three times per week.

PMID- 11513187
TI  - Chronic hepatitis C in ethnic minority patients evaluated in Los Angeles County.
AB  - OBJECTIVE: The aim of this study was to compare demographic, clinical, and
      histological features of hepatitis C in four ethnic groups seen at the Los
      Angeles County/University of Southern California Hepatitis Clinic. METHODS: We
      evaluated 256 patients with chronic hepatitis C, with 132 (52%) receiving a liver
      biopsy as part of their evaluation. We estimated fibrosis progression in 103
      patients with known duration of disease. RESULTS: Asians (6%) were
      underrepresented in the hepatitis C cohort, whereas Latinos (51%) were
      overrepresented, as compared with the entire county population. A history of
      injection drug use was more frequent in whites (65%) than in African Americans
      (45%, p = 0.05), Latinos (47%, p = 0.01), or Asians (0%) and more frequent in
      Latinos (59%) than in Latinas (26%, p = 0.003). Such a gender difference was not
      found in African Americans or whites. Baseline laboratory values were comparable.
      The amount of alcohol consumed daily was higher in African Americans than in
      Asians (p = 0.0001) and whites (p = 0.10). African Americans (0.077 fibrosis
      stages/yr) and whites (0.084/yr) had significantly lower mean estimated
      progression of liver fibrosis than Latinos (0.215/yr) with hepatitis C virus
      infection (ps = 0.03 and 0.02, respectively): this was likely related to their
      longer estimated duration of disease. CONCLUSION: Minorities represent the
      majority of chronic hepatitis C cases in the Los Angeles County Hepatitis Clinic.
      Asians, Latinas, and African Americans are less likely to report injection drug
      use as a risk factor for hepatitis C virus. Latinos seem to have faster liver
      fibrosis progression rates than either African Americans or whites.

PMID- 11513188
TI  - Effects of ascites resolution after successful TIPS on nutrition in cirrhotic
      patients with refractory ascites.
AB  - OBJECTIVE: Malnutrition is common in patients with decompensated cirrhosis and
      refractory ascites. The use of transjugular intrahepatic portosystemic stent
      shunt (TIPS) is effective in eliminating ascites. The purpose of this study was
      to investigate the effect of TIPS and resolution of refractory ascites on the
      nutritional status of patients with decompensated cirrhosis. METHODS: Fourteen
      consecutive patients with refractory ascites and a Pugh score of 9.0+/-0.5 had a
      TIPS insertion. Biochemical data, resting energy expenditure (REE), total body
      nitrogen (TBN), body potassium (TBK), body fat (TBF), muscle force (MF), and food
      intake were recorded before TIPS, and at 3 and 12 months after the procedure.
      RESULTS: Ten patients completed the study. Baseline values for REE, TBN, TBF, MF,
      and energy intake were below normal at baseline. There was a significant increase
      in dry weight, TBN, and REE at 3 and 12 months compared with baseline. TBF
      improved significantly at 12 months. There was a trend toward an increase in
      energy intake (p = 0.072). There was no change in protein intake, TBK, MF, and
      Pugh score. CONCLUSION: In cirrhotic patients with refractory ascites, resolution
      of the ascites after TIPS placement resulted in improvement of several
      nutritional parameters, especially for body composition.

PMID- 11513189
TI  - Hyperferritinemia, iron overload, and multiple metabolic alterations identify
      patients at risk for nonalcoholic steatohepatitis.
AB  - OBJECTIVE: The aim of this study was to define in patients with hyperferritinemia
      and normal transferrin saturation the relationships among hyperferritinemia, iron
      overload, HFE gene mutations, the presence of metabolic alterations, and
      nonalcoholic steatohepatitis (NASH). METHODS: Forty patients with increased serum
      ferritin, resistant to dietary restriction and normal transferrin saturation, 90
      with ultrasonographic evidence of hepatic steatosis, and 60 obligate
      heterozygotes for hemochromatosis, all negative for alcohol abuse, hepatitis
      virus infections, and inflammation were studied. Transferrin saturation, serum
      ferritin, uric acid, lipids, glucose tolerance, insulin resistance, HFE gene
      mutations, liver histology, and hepatic iron concentration were analyzed.
      RESULTS: Of the 40 patients with hyperferritinemia, 29 (72%) had biochemical
      metabolic abnormalities, 18 of the 26 examined (69%) had insulin resistance, 26
      (65%) had the presence of one of the two HFE gene mutations (normal controls, 33
      of 128 [26%], p < 0.0001), and all had increased liver iron concentration. Thirty
      one patients (77%) had histology compatible with NASH. At univariate analysis,
      NASH was significantly associated with the presence of metabolic alterations, the
      C282Y mutation, and severity of fibrosis. At multivariate analysis, NASH was
      associated with the coexistence of multiple metabolic alterations (odds ratio =
      5.2, 95% CI = 0.95-28.7). The risk of having NASH augmented in the presence of
      higher values of ferritin and liver iron concentration. Among the 90 patients
      with ultrasonographic evidence of hepatic steatosis, 24 (27%) had increased serum
      ferritin with normal transferrin saturation, but only six remained
      hyperferritinemic after dietary restriction. CONCLUSION: Increased ferritin with
      normal transferrin saturation is frequently found in patients with hepatic
      steatosis, but it reflects iron overload only in those patients in whom it
      persists despite an appropriate diet. The simultaneous disorder of iron and
      glucose and/or lipid metabolism, in most of the cases associated with insulin
      resistance, is responsible for persistent hyperferritinemia and identifies
      patients at risk for NASH.

PMID- 11513190
TI  - Impairment of metabolic function in chronic hepatitis C is related to factors
      associated with resistance to therapy.
AB  - OBJECTIVE: Liver disease causes a loss of hepatic function, and remission is
      associated with improved functional hepatic mass. The object of the present study
      was to investigate whether liver metabolic function assessed by antipyrine
      clearance is related to other disease characteristics influencing response to
      therapy in chronic hepatitis C. METHODS: Patients (n = 96) received three
      different treatment regimens: one group received interferon alfa-2b for 48 wk; in
      a second group with maintained positive hepatitis C virus (HCV) RNA after 12 wk,
      interferon was combined for 36 wk with oral ribavirin; and patients who were
      relapsers or nonresponders to a previous therapy with interferon alone received
      interferon alfa-2b plus ribavirin for 48 wk. RESULTS: Twenty-five patients (26%)
      showed sustained normalization of ALT levels and negative HCV RNA 6 months after
      therapy. The response was more likely to be sustained in patients with a genotype
      other than 1 (52.0% vs 15.5% in patients with genotype 1, p < 0.001), and the
      percentage of sustained responders was higher among patients who demonstrated
      negativity of HCV RNA at the end of 4 wk of treatment (64% vs 13% without
      negativity, p < 0.001). Sustained response was associated with significantly
      lower baseline serum ferritin (-46%, p < 0.01) and duration of infection (-33%, p
      < 0.01). Baseline antipyrine clearance was higher in sustained responders than in
      nonresponders (+19%, p < 0.05) and lower in genotype 1 patients than in those
      with a genotype other than 1 (-24%, p < 0.05). Antipyrine clearance increased by
      12% at the end of the 48-wk course of treatment among sustained responders (+34%
      vs nonresponders, p < 0.001) and still remained elevated at the end of the follow
      up (+35% vs nonresponders, p < 0.001). CONCLUSION: In summary, the present study
      shows that liver oxidative metabolism is related to antiviral response rates and
      suggests that much of the effect is explained by viral genotype.

PMID- 11513191
TI  - The role of diabetes in hepatocellular carcinoma: a case-control study among
      United States Veterans.
AB  - OBJECTIVE: Diabetes mellitus (DM) has been reported to increase the risk of
      hepatocellular carcinoma (HCC). We carried out a case-control study to examine
      the role of DM while controlling for several known risk factors of HCC. METHODS:
      All hospitalized patients with primary liver cancer (PLC) during 1997-1999 were
      identified in the computerized database of the Department of Veterans Affairs,
      the Patient Treatment File. Controls without cancer were randomly assigned from
      the Patient Treatment File during the same time period. The inpatient and
      outpatient files were searched for several conditions including DM, hepatitis C
      virus (HCV), hepatitis B virus (HBV), alcoholic cirrhosis, autoimmune hepatitis,
      hemochromatosis, and nonspecific cirrhosis. Adjusted odds ratios (OR) were
      calculated in a multivariable logistic regression model. RESULTS: We identified
      823 patients with PLC and 3459 controls. The case group was older (62 yr [+/-10]
      vs 60 [+/-11], p < 0.0001), had more men (99% vs 97%, 0.0004), and a greater
      frequency of nonwhites (66% vs 71%, 0.0009) compared with controls. However, HCV-
      and HBV-infected patients were younger among cases than controls. Risk factors
      that were significantly more frequent among PLC cases included HCV (34% vs 5%, p
      < 0.0001), HBV (11% vs 2%, p < 0.0001), alcoholic cirrhosis (47% vs 6%, p <
      0.0001), hemochromatosis (2% vs 0.3%, p < 0.0001), autoimmune hepatitis (5% vs
      0.5%, p < 0.0001), and diabetes (33% vs 30%, p = 0.059). In the multivariable
      logistic regression, diabetes was associated with a significant increase in the
      adjusted OR of PLC (1.57, 1.08-2.28, p = 0.02) in the presence of HCV, HBV, or
      alcoholic cirrhosis. Without markers of chronic liver disease, the adjusted OR
      for diabetes and PLC was not significantly increased (1.08, 0.86-1.18, p = 0.4).
      There was an increase in the HCV adjusted OR (17.27, 95% Cl = 11.98-24.89) and
      HBV (9.22, 95% CI = 4.52-18.80) after adjusting for the younger age of HCV- and
      HBV-infected cases. The combined presence of HCV and alcoholic cirrhosis further
      increases the risk with an adjusted OR of 79.21 (60.29-103.41). The population
      attributable fraction for HCV among hospitalized veterans was 44.8%, whereas that
      of alcoholic cirrhosis was 51%. CONCLUSION: DM increased the risk of PLC only in
      the presence of other risk factors such as hepatitis C or B or alcoholic
      cirrhosis. Hepatitis C infection and alcoholic cirrhosis account for most of PLC
      among veterans.

PMID- 11513192
TI  - Changes in serum lipoprotein profile during interferon therapy in chronic
      hepatitis C.
AB  - OBJECTIVES: Therapy with a interferon is associated with a rise in serum
      triglyceride levels, although this effect has not been well studied with newer
      forms of interferon or interferon in combination with ribavirin. METHODS: Review
      of combined data obtained from several prospective, randomized controlled
      clinical trials conducted in the clinical studies unit of a tertiary care
      referral center among patients with chronic hepatitis C undergoing treatment with
      various forms of a interferon, with or without the addition of ribavirin. Serum
      levels of triglycerides and cholesterol were measured before and during therapy.
      Changes in these levels were correlated with baseline characteristics. RESULTS:
      At baseline, the mean serum triglyceride level among 152 patients studied was 130
      mg/dL (range 32-620) and was elevated above normal in three patients (2%). During
      therapy, triglyceride levels rose significantly early on and began to decline
      spontaneously after 12 wk, returning to baseline after stopping treatment.
      Triglyceride levels rose above 500 mg/dL in 18 patients (12%) and above 1000
      mg/dL in two patients (1.3%) although none experienced acute complications or
      clinical symptoms. Serum cholesterol levels did not change significantly during
      therapy (mean at baseline 172 vs 168 mg/dL at 24 wk). Factors correlated with the
      rise in triglycerides included baseline triglyceride levels, HCV genotype, and
      the type of interferon used. CONCLUSIONS: Serum triglyceride levels increase
      consistently in patients with chronic hepatitis C treated with all forms of a
      interferon, often to very high levels. These changes do not seem to be associated
      with clinical signs or complications and triglyceride levels decline while
      patients are still on therapy and return to normal after stopping.

PMID- 11513193
TI  - A pilot trial of recombinant interleukin-12 in patients with chronic hepatitis C
      who previously failed treatment with interferon-alpha.
AB  - OBJECTIVE: Interleukin-12 is a cytokine with a multitude of immunomodulatory
      actions. Currently, interferon-alpha (IFN-alpha) monotherapy and combination
      treatment with IFN and ribavirin are the only therapies with proven efficacy
      against chronic hepatitis C infection. The purpose of this study was to assess
      the safety and antiviral activity of recombinant interleukin-12 (rhIL-12) in
      adults with chronic hepatitis C who did not achieve a sustained response to
      previous IFN-alpha therapy. METHODS: This was a randomized, placebo-controlled,
      double-blind trial. We randomized 24 patients to one of three dose groups: 30
      ng/kg, 100 ng/kg, and 300 ng/kg. Within each group, six patients received rhIL
      12, and two patients received placebo administered s.c. twice a week for 12 wk.
      RESULTS: Three of six patients treated with rhIL-12 at a dose of 300 ng/kg had
      loss of detectable hepatitis C RNA by reverse transcription-polymerase chain
      reaction compared with the placebo group (p = 0.05). All patients relapsed at the
      end of the 3-month treatment period. No other dose group demonstrated a loss of
      detectable hepatitis C RNA. CONCLUSIONS: RhIL-12 at 300 ng/kg can suppress
      hepatitis C RNA to undetectable levels by reverse transcription-polymerase chain
      reaction, although relapse occurred when treatment was stopped. RhIL-12 was well
      tolerated with the most common side effects being flu-like symptoms and
      headaches.

PMID- 11513194
TI  - A phenotypic change of small intestinal epithelium to colonocytes in small
      intestinal adenomas and adenocarcinomas.
AB  - OBJECTIVE: Using a novel monoclonal antibody (mAb Das-1) that specifically reacts
      with colon epithelium, we examined if there is a phenotypic change of small
      intestinal enterocytes toward colonocytes in small intestinal neoplastic tissue.
      METHODS: Tissue sections of the small intestine consisting of adenomas (n = 20,
      five with histories of familial polyposis), adenocarcinomas (eight primary and
      one metastatic from colon). carcinoids (n = 2), and hyperplastic polyps (n = 3)
      were examined by a sensitive immunoperoxidase assay using mAb Das-1 (IgM
      isotype). Normal jejunal (n = 10) and colonic (n = 10) biopsy specimens were also
      included as additional controls. RESULTS: mAb Das-1 reacted with normal colonic
      epithelium but not with jejunal mucosa. However, mAb Das-1 reacted strongly with
      each of the five adenomas (100%) from patients with histories of familial
      polyposis, but only five of 15 (33%) of the adenomas from nonfamilial polyposis
      patients, and each of the eight (100%) adenocarcinomas of the small intestine (p
      < 0.001). The reactivity with the adenomas from nonfamilial polyposis patients
      was very focal, whereas in the adenomas with familial polyposis the reactivity
      was more extensive. Each of the eight carcinomas reacted strongly with mAb Das-1.
      Adjacent normal small intestinal mucosa did not react. Hyperplastic polyps and
      the carcinoids did not react with mAb Das-1. CONCLUSION: These data demonstrate a
      phenotypic change in small intestinal epithelium toward the colonic phenotype,
      particularly in familial polyposis and in adenocarcinomas. mAb Das-1 may be
      clinically useful in identifying small intestinal adenomas with "high risk" for
      malignancy, such as in familial polyposis.

PMID- 11513195
TI  - The enema.

PMID- 11513196
TI  - Hemochromatosis with HFE gene mutation in a Japanese patient.
AB  - A case of hemochromatosis associated with HFE gene mutation has never been
      previously reported in a Japanese patient. A 65-yr-old Japanese woman presenting
      with primary hemochromatosis underwent HFE mutation analyses, which demonstrated
      a C282Y mutation, this being the definitive gene mutation of Caucasian
      hemochromatosis.

PMID- 11513197
TI  - Hepatitis C, cryoglobulinemia, and cutaneous vasculitis associated with unusual
      and serious manifestations.
AB  - Hepatitis C viral infection is currently the leading cause of chronic hepatitis
      and cirrhosis. It also is a major predisposing factor for the development of
      hepatocellular carcinoma. It is estimated that approximately 1-2% of patients
      with hepatitis C infection have nonhepatic manifestations that are protean in
      nature. In this report, we describe six unusual cases of nonhepatic
      manifestations: abdominal vasculitis in two, peripheral neuropathy in two, and
      one patient each with central nervous system vasculitis and necrotizing cutaneous
      vasculitis. All patients had cutaneous vasculitis and cryoglobulinemia. None of
      our patients had cirrhosis, yet three of the six patients died. Because of the
      severe manifestations, aggressive therapy was instituted with interferon,
      immunosuppressive medications, i.v. immunoglobulin, and plasmapheresis. Our
      report underscores the importance of recognizing nonhepatic manifestations in
      patients with hepatitis C infection that may be associated with high morbidity
      and mortality.

PMID- 11513198
TI  - Severe hepatotoxicity with jaundice associated with paroxetine.
AB  - Hepatotoxicity due to paroxetine, a selective serotonin reuptake inhibitor, is
      very rare, and to the best of our knowledge, only five cases of liver injury in
      association with paroxetine have previously been reported in the medical
      literature. We describe the clinical, biochemical, and pathological findings in a
      patient with paroxetine hepatotoxicity, which was reversed after withdrawal of
      the drug. The present case and the others previously reported suggest that
      hepatotoxicity should be taken into account as a rare complication, sometimes
      severe, that may occur with paroxetine.

PMID- 11513199
TI  - 18F-Fluorodeoxyglucose PET in a patient with primary small bowel lymphoma: the
      only sensitive method of imaging.
AB  - This report describes the case of a patient with primary small bowel lymphoma.
      Well-established methods of imaging did not give a hint on diagnosis. Increased
      18F-fluorodeoxyglucose uptake was visualized on performance of positron emission
      tomography, corresponding with the intraoperatively found tumorous process. The
      present case points to a potential superiority of positron emission tomography in
      visualizing primary small bowel lymphoma.

PMID- 11513200
TI  - H. pylori eradication: new role for the pharmacist?

PMID- 11513201
TI  - Diagnosis of pancreatic cancer-EUS/FNA to the rescue?

PMID- 11513202
TI  - Cardiac abnormalities in cirrhosis.

PMID- 11513203
TI  - Re: Pimentel et al.--Eradication of small intestinal bacterial overgrowth reduces
      symptoms of irritable bowel syndrome.

PMID- 11513204
TI  - Small intestinal bacterial overgrowth and the irritable bowel syndrome.

PMID- 11513205
TI  - Adult fibrosing colonopathy associated with mesalazine treatment.

PMID- 11513206
TI  - Re: Anderson et al.--Women, BMI, and colonoscopy.

PMID- 11513207
TI  - Re: Triantafillidis et al.--Acute idiopathic pancreatitis complicating active
      Crohn's disease: favorable response to infliximab treatment.

PMID- 11513208
TI  - Enteroscopic findings of intestinal ischemia.

PMID- 11513209
TI  - Watermelon stomach and familial Mediterranean fever.

PMID- 11513210
TI  - Helicobacter pylori, cell proliferation, and carcinogenesis.

PMID- 11513211
TI  - Helicobacter pylori stool antigen (HpSA) test in children with recurrent
      abdominal pain.

PMID- 11513212
TI  - Assessment of intestinal permeability with lactulose/mannitol: gum chewing is a
      potential confounding factor.

PMID- 11513213
TI  - Sildenafil-induced esophageal ulcers.

PMID- 11513214
TI  - Hemorrhoidal bleeding associated with sildenafil.

PMID- 11513215
TI  - Leptin in nonalcoholic steatohepatitis: is it one of the "hits"?

PMID- 11513216
TI  - Inflammatory pseudotumor of the liver as the first manifestation of Crohn's
      disease.

PMID- 11513217
TI  - Re: Celiac sprue: another autoimmune syndrome associated with hepatitis C.

PMID- 11513218
TI  - Re: Koshy et al.--Propofol versus midazolam and meperidine for conscious sedation
      in GI endoscopy.

PMID- 11513219
TI  - Re: Thompson--The knife is better than nitro.

PMID- 11513220
TI  - Polymorphisms of the CCK, CCKAR and CCKBR genes: an association with alcoholism
      study.
AB  - OBJECTIVE: Cholecystokinin (CCK) plays an important role in the functioning of
      the central nervous system via an interaction with dopamine and other
      neurotransmitters. The dopaminergic system has been implicated in the maladaptive
      behaviors associated with drugs of abuse (e.g., alcohol and cocaine). We analyzed
      genetic variations in the promoter and coding regions of the CCK, CCKA-receptor
      (CCKAR) and CCKB-receptor (CCKBR) genes, and performed association analyses with
      alcoholism. METHOD: A total of 214 Japanese male patients with alcoholism (93
      with delirium tremens, 49 with hallucinations, 38 with seizures and 83 without
      any of these symptoms) and 98 age-matched Japanese male controls were examined
      using PCR-based Single Strand Conformational Polymorphism (SSCP) analysis.
      RESULTS: A total of 8 variants in the CCK gene, 11 variants in the CCKAR gene and
      9 variants in the CCKBR gene were detected in the present study. Nominally
      significant differences between alcoholics and controls were found at the -85
      locus of the CCKAR gene (p = .035). In addition, patients displaying
      hallucinations showed a higher frequency of the homozygous genotype of the allele
      (GT)8 at the -388 locus of the CCKAR gene (p = .042) and homo- and heterozygous
      genotypes of the T allele at the -333 locus (p = .025), relative to other
      patients. However, these differences were not significant after Bonferroni
      correction. CONCLUSIONS: Our data suggest that polymorphisms of the CCK, CCKAR
      and CCKBR genes do not play a major role in alcohol withdrawal symptoms (even
      though significant associations were found among polymorphisms at the -388 and 
      333 loci of the CCKAR gene and hallucinations, the rate was nonsignificant after
      Bonferroni correction).

PMID- 11513221
TI  - Interviewers' and respondents' effects on self-reported alcohol consumption in a
      Swiss health survey.
AB  - OBJECTIVE: Characteristics of interviewers and respondents have been shown to
      influence the quality of data from survey research in various domains. There is
      little evidence for such effects in alcohol research, however. The purpose of the
      study reported here was to examine effects of gender and age of interviewers and
      respondents simultaneously This was done using hierarchical linear modeling, the
      advantage of which is that it can account for the clustering effects of
      respondents being nested within interviewers. METHOD: Data were obtained from the
      first wave of an ongoing randomized longitudinal study on changes in alcohol
      consumption in Switzerland. The response rate was 77.9%. Analyses were based on
      2,746 (1,749 male) subjects with an average of at least monthly consumption in
      the 6 months before the telephone interview. Consumption was assessed by means of
      a graduated frequency measure. Five different hierarchical linear models of
      increasing complexity were used to test several hypotheses of interviewer and
      respondent effects. Findings from hierarchical linear modeling were compared with
      those from "classical" analysis of variance. RESULTS: A theoretical design effect
      of 1.89 attributable to interviewers was found. Both analyses of variance and
      hierarchical linear modeling provide support for a structure with a main effect
      for gender of respondents, as well as a main effect for age of respondents and an
      interaction effect between interviewers' and respondents' ages. CONCLUSIONS:
      Interviewer effects affect the estimation of statistics in survey research and
      must be adjusted for either by means of multilevel analysis or by the use of
      specialized sample survey software.

PMID- 11513222
TI  - Alcohol drinking patterns among Jewish and Arab men and women in Israel.
AB  - OBJECTIVE: Jews and Muslim Arabs comprise the bulk of modern Israeli society.
      Jewish tradition permits controlled alcohol drinking, whereas Muslim tradition
      prohibits the use of any alcohol. Increasing exposure of the traditionally
      conservative Arab sector to the Western culture of modern Israel might impact on
      and be reflected in the drinking patterns of these two populations. The influence
      of religiosity and other factors on drinking patterns of Jewish and Arab adults
      are examined using data from a 1995 national household survey. METHOD: Past month
      drinking is assessed in this nationally representative sample of nearly 5,000
      Jews and 1,000 Arabs (N = 5,954, 60% women). Unadjusted and adjusted odds ratios
      (ORs) are presented to describe associations between any and heavy drinking and
      nationality group, religiosity, education and marital status among men and women.
      Modification of the nationality-drinking relationship by religiosity is also
      examined. RESULTS: Any past-month drinking was reported more often by Jewish
      respondents than Arab respondents (OR = 2.9, 95% Cl: 2.5-3.4), and this
      difference remained statistically significant after accounting for the effects of
      the other covariables. This cross-nationality difference was more pronounced
      among women (OR = 6.4, 95% Cl: 4.6-8.8) than men (OR = 2.3, 95% CI: 1.8-2.9). The
      proportion of drinkers who reported heavy drinking in the past month, however,
      was lower among Jews (OR = 0.3, 95% CI: 0.2-0.4). Significantly higher rates of
      drinking were noted for secular men and women than for religious respondents in
      both nationality groups. Rates of drinking were more similar among secular Arabs
      and Jews than among religious respondents of these nationality groups.
      CONCLUSIONS: These results add support to the theory that adherence to religious
      traditions continues to serve as a barrier against drinking among both Arabs and
      Jews. Further work is required to determine if these patterns are stable over
      time and whether genetic factors are contributing to the sociocultural
      influences.

PMID- 11513223
TI  - Drinking patterns among Hispanic adolescents: results from a national household
      survey.
AB  - OBJECTIVE: This is one of the first studies to examine and compare alcohol use
      for adolescent Cubans, Mexican Americans, Puerto Ricans and other Hispanics.
      METHOD: The data come from the 1993 National Household Survey on Drug Abuse
      (NHSDA), a national probability sample of the U.S. household population. The
      sample examined here (N = 1,865, 52% male) comprises 200 Cubans, 1,133 Mexican
      Americans, 255 Puerto Ricans and 277 Central/South Americans who were 12 to 17
      years old. Drinking patterns are measured using a quantity-frequency index, and
      analyses are conducted using Stata. RESULTS: In the cross-tabulations, no ethnic
      differences in drinking patterns are found for males or females, nor is there
      evidence of gender differences within ethnic groups, although there are some age
      differences in alcohol use. In the logistic regression analyses, two ethnic
      differences emerge, although the factors most consistently associated with
      drinking behaviors in these analyses are age, Spanish language use and urban
      residence. Additional analyses using the 1998 NHSDA suggest that ethnic
      differences in alcohol use may emerge in late adolescence/early adulthood.
      CONCLUSIONS: Given the established findings of ethnic and gender differences in
      drinking among adult Hispanics, it is surprising that few differences are
      evidenced in adolescence. Future research should explore whether such differences
      emerge during the transition into adulthood and, if so, identify factors that
      produce them. In addition, to increase understanding of these ethnic groups'
      drinking patterns, future research should further investigate the factors
      associated with Hispanic adolescents' alcohol use, including both consideration
      of whether the predictors are the same across groups and of the role of
      sociocultural factors.

PMID- 11513224
TI  - Alcohol consumption and health-promoting behavior in a U.S. household sample:
      leisure-time physical activity.
AB  - OBJECTIVE: Hypothesizing that people who moderate their alcohol intake engage in
      other health-promoting cardioprotective behavior, this research explored
      associations between alcohol consumption and leisure-time physical activity.
      METHOD: Data representative of the U.S. population (N = 41,104; 52.5% women) were
      derived from the 1990 National Health Interview Survey, which employed a
      multistage probability design. Multivariate logistic regression analyses were
      performed, using lifetime abstainers as the reference group. RESULTS: An inverted
      J-shaped curve characterized the association between estimates of alcohol
      consumption and leisure-time physical activity, in which likelihood of displaying
      a physically active lifestyle (odds ratios) increased from abstinence (1.00) to
      moderate drinking (1.84), then declined at heavier consumption (1.61). Stratified
      analyses yielded similar results with peaks at light or moderate consumption for
      current smokers, persons aged 55 and over, and those with cardiovascular risk
      conditions. As activity intensity increased, the inverted J-shaped curve
      persisted with more pronounced peaks at moderate drinking. CONCLUSIONS: Robust
      findings of an association between cardioprotective leisure-time physical
      activity and moderate alcohol consumption provide evidence for a health-promoting
      lifestyle that may play an explanatory role in the alcohol-coronary heart disease
      relationship.

PMID- 11513225
TI  - Correlates of unpredicted outcomes in sons of alcoholics and controls.
AB  - OBJECTIVE: Several risk factors for alcohol abuse and dependence have been
      identified, including a family history of the disorder and a low response to
      alcohol. However, not everyone with these attributes develops an alcohol use
      disorder and some alcoholics have neither characteristic. This article evaluates
      factors that might have contributed to unexpected outcomes, in a prospective
      study of sons of alcoholics and controls. METHOD: 411 men with complete data at
      baseline (Time 1 or T1) and at 15-year (Time 15 or T15) follow-ups were studied
      using the level of response (LR) to alcohol, the family history (FH) of
      alcoholism, and additional alcohol and drug-related experiences at T1. T15 data
      included the development of alcohol abuse or dependence, along with the 15-year
      functioning in six domains for the subject, as well as the characteristics of his
      spouse. The men were divided into groups based on the presence of two major risk
      factors, low LR and FH, after controlling for several other characteristics,
      including antisocial personality disorder. RESULTS: Rates of alcohol use
      disorders increased across Group 1 (family history negative [FHN] and no low LR),
      Group 2 (either family history positive [FHP] or low LR, but not both) and Group
      3 (both FHP and low LR). After controlling for FH and LR for Group 1, only T1
      drinking quantity and T15 positive alcohol expectancies related to a diagnosis,
      but explained only 12% of the variance. The results improved to R2's of 0.26 and
      0.36 for Groups 2 and 3, with additional predictors including the T1 history of
      alcohol problems and T15 measures of poor coping mechanisms, higher drinking in
      the environment and less nurturance in the social support system. CONCLUSIONS:
      Procedures aimed at discouraging earlier heavier drinking, altering attitudes
      toward alcohol early in life, teaching appropriate coping methods and developing
      support systems might help individuals carrying multiple risk factors to become
      more resilient.

PMID- 11513226
TI  - Gender differences in the prediction of problem alcohol use in adulthood:
      exploring the influence of family factors and childhood maltreatment.
AB  - OBJECTIVE: The purpose of this study was to contrast men and women in prospective
      relationships among family-oriented and alcohol-related variables obtained during
      adolescence, childhood physical, emotional and sexual abuse collected
      retrospectively, and later adult problem alcohol use. METHOD: In structural
      equation models, early family processes (support/bonding, parent drug-use
      problems, parental divorce and childhood maltreatment) and prior alcohol use
      simultaneously predicted adult problem alcohol use at two later time points in a
      longitudinal community sample of 426 (305 female) adults. RESULTS: Significant
      relationships were found among family processes, childhood maltreatment, and
      problem alcohol use within time and longitudinally for both men and women.
      Greater family support/bonding during adolescence predicted less problem alcohol
      use in adulthood. Men and women who experienced sexual abuse as a child reported
      more problem alcohol use in adulthood. Problem alcohol use was stable across
      time. Men reported more problem alcohol use in adolescence and adulthood, and
      women reported more early sexual abuse. These results contradict those that find
      no significant relationships between childhood abuse and subsequent alcohol
      related problems. Parental drug use problems during the participant's adolescence
      did not directly predict problem alcohol use in adulthood. The relationship was
      more indirect in that parental drug use was associated with family-related
      concomitants that in turn were significant predictors of more problem alcohol use
      in adulthood. CONCLUSIONS: The strong stability for problem alcohol use across
      the three time periods is a signal that alcohol use in adolescence should not be
      ignored; furthermore, family dynamics need attention in addressing problem
      alcohol use.

PMID- 11513227
TI  - Personality characteristics and alcohol consumption: longitudinal analyses in men
      and women followed from ages 13 to 32.
AB  - OBJECTIVE: The purpose of the present study was to investigate the relation
      between personality characteristics and alcohol consumption. Using a general
      population of young and generally healthy men and women, the focus was not on
      alcoholism but on the full scope of alcohol consumption, including abstinence and
      moderate levels of consumption. Modification of the relation between personality
      and alcohol consumption by gender, age and type of beverage was investigated.
      METHOD: The population consisted of 483 (259 female) subjects from the Amsterdam
      Growth and Health Longitudinal Study; they were aged 13 to 32 years over the 20
      year course of the study, during which span measurements were taken between two
      and seven times. The longitudinal relation between five subscales of the Dutch
      Personality Inventory (DPI) and alcohol consumption were assessed with
      generalized estimating equations. RESULTS: Low prevalence of heavy alcohol
      consumption was found in this population. Abstinence from alcohol was more common
      among subjects who scored higher on Social Inadequacy, Rigidity and Self
      sufficiency subscales. The amount of alcohol consumed was higher in drinkers who
      scored low on Rigidity and Social Inadequacy. Gender, age and type of alcoholic
      beverage modified some of the found relationships (e.g., adult women who scored
      high on Dominance were more likely to be the firmer wine drinkers). No
      significant relationships were found between alcohol consumption and the DPI
      Inadequacy subscale. CONCLUSIONS: Alcohol consumption was associated with lower
      scores on Social Inadequacy, Rigidity and Self-sufficiency.

PMID- 11513228
TI  - Life events and alcohol consumption among mature adults: a longitudinal analysis.
AB  - OBJECTIVE: Four waves of the Health and Retirement Study were used to examine
      changes in alcohol consumption co-occurring and following stress associated with
      major health, family and employment events. METHOD: The final sample consisted of
      7,731 (3,907 male) individuals between the ages of 51 and 61 at baseline. We used
      multinomial logit analysis to study associations between important life events
      and changes in alcohol consumption over a 6-year study period. Interactions
      between stressful life events, gender and problem drinking were also evaluated.
      RESULTS: Most persons (68%) did not change their use of alcohol over the entire 6
      years. Hospitalization and onset of a chronic condition were associated with
      decreased drinking levels. Retirement was associated with increased drinking.
      Widowhood was associated with increased drinking but only for a short time.
      Getting married or divorced was associated with both increases and decreases in
      drinking, with a complex lag structure. A history of problem drinking influenced
      the association between certain life events (e.g., divorce and retirement) and
      changes in drinking. Gender modified the association between losing a spouse and
      changes in drinking. CONCLUSIONS: Even after controlling for problem drinking
      history, social support and coping skills, changes in drinking behavior were
      related to several life events occurring over a 6-year period for a national
      cohort of individuals in late middle-age. The magnitude of these relationships,
      however, varied by gender and problem drinking history.

PMID- 11513229
TI  - DSM-IV alcohol dependence and sustained reduction in drinking: investigation in a
      community sample.
AB  - OBJECTIVE: A common clinical conception of alcohol dependence is that it is
      chronic, and the idea of impaired control figures prominently in an influential
      definition of alcohol dependence. We investigated the meaning of a diagnosis of
      DSM-IV alcohol dependence in untreated individuals. METHOD: Household residents
      screened for elevated drinking were assessed for DSM-IV alcohol dependence and re
      interviewed 1 year later. We report on 115 subjects with and 460 subjects without
      current DSM-IV alcohol dependence at baseline. Follow-up drinking indicators
      included a measure of sustained reduction in drinking. RESULTS: No support was
      found for a lower probability of sustained reduction in drinking at follow-up
      among the group with baseline DSM-IV alcohol dependence. Significant group
      differences indicated that the dependent group was more likely to reduce
      drinking. CONCLUSIONS: A diagnosis of DSM-IV alcohol dependence among untreated
      individuals implies a prognosis that is different from that for the same
      diagnosis among those seen in treatment settings. This does not necessarily
      indicate that the diagnosis is invalid, but rather suggests that risk factors for
      chronic course are more applicable to cases of DSM-IV alcohol dependence seen in
      treatment settings.

PMID- 11513230
TI  - Meta-Analysis of social relationships and posttreatment drinking outcomes:
      comparison of relationship structure, function and quality.
AB  - OBJECTIVE: Alcoholism treatment programs are recognizing the importance of social
      relationships by addressing interpersonal as well as intrapersonal factors in
      treatment. This shift in treatment orientation is occurring, however, in the
      absence of extensive information on the magnitude of the relationship between
      interpersonal factors and drinking outcomes. This article examines the
      association between alcoholism treatment drinking outcomes and social
      relationships. METHOD: Studies of the relationship between drinking outcomes and
      social relationships reported from 1965 to 1996 were coded for inclusion in this
      study. Analysis was a conceptually based meta-analytic review and synthesis of
      some of these findings. Through illustration, the manner in which components of
      social relationships (structure, function and quality) are associated with
      drinking outcomes was analyzed. RESULTS: Marital status, a structural construct,
      was less strongly correlated with drinking outcomes (average r = 0. 11) than was
      social support, a functional construct (average r = 0.22) or marital and family
      adjustment, a construct indicative of quality (average r = 0.17). Marital status
      was more strongly related to drinking outcomes for men than for women, whereas
      having significant others in treatment predicted stronger relationships between
      drinking outcomes and both social support and marital/family adjustment for both
      genders. CONCLUSIONS: The effect of social relationships on drinking outcomes is
      variable, inconsistent and weak. That this is not the case for some
      subpopulations and constructs encourages us to continue the examination of these
      complex interrelationships.

PMID- 11513231
TI  - Can targeting nondependent problem drinkers and providing internet-based services
      expand access to assistance for alcohol problems? A study of the moderation
      management self-help/mutual aid organization.
AB  - OBJECTIVE: Moderation Management (MM) is the only alcohol self-help organization
      to target nondependent problem drinkers and to allow moderate drinking goals.
      This study evaluated whether MM drew into assistance an untapped segment of the
      population with nondependent alcohol problems. It also examined how access to the
      organization was influenced by the provision of Internet-based resources. METHOD:
      A survey was distributed to participants in MM face-to-face and Internet-based
      self-help groups. MM participants (N = 177, 50.9% male) reported on their
      demographic characteristics, alcohol consumption, alcohol problems and
      utilization of professional and peer-run helping resources. RESULTS: MM appears
      to attract women and young people, especially those who are nondependent problem
      drinkers. It was also found that a significant minority of members experienced
      multiple alcohol dependence symptoms and therefore may have been poorly suited to
      a moderate drinking program. CONCLUSIONS: Tailoring services to nondependent
      drinkers and offering assistance over the Internet are two valuable methods of
      broadening the base of treatment for alcohol problems. Although interventions
      like MM are unlikely to benefit all individuals who access them, they do attract
      problem drinkers who are otherwise unlikely to use existing alcohol-related
      services.

PMID- 11513232
TI  - Deficits in recognition of emotional facial expression are still present in
      alcoholics after mid- to long-term abstinence.
AB  - OBJECTIVE: Emotional facial expression (EFE) decoding skills play a key role in
      interpersonal relationships. Decoding errors have been described in several
      pathological conditions, including alcoholism. The aim of this study was to
      investigate whether EFE decoding skill deficits persist after abstention from
      alcohol of at least 2 months. METHOD: Alcoholic patients abstinent for at least 2
      months (n = 25) were compared with 25 recently detoxified patients and with 25
      normal controls matched for age, gender and educational level. Subjects were
      presented with 40 photographs of facial expressions portraying happiness, anger,
      sadness, disgust and fear. Each emotion was displayed with neutral, mild,
      moderate and strong emotional intensity. Each facial expression was judged
      successively on eight scales labeled happiness, sadness, fear, anger, disgust,
      surprise, shame and contempt. For each scale, subjects rated the estimated
      intensity level. A complementary scale assessed the self-estimated difficulty in
      performing the task. RESULTS: Recently detoxified alcoholics were significantly
      less accurate than controls, making more EFE labeling errors and overestimating
      the intensity of the portrayed emotions. Deficits in decoding accuracy for anger
      and disgust were present in mid- to long-term abstinent patients; intensity
      overestimation was present in the former and absent in the latter. CONCLUSIONS:
      Deficits in decoding accuracy for anger and disgust, and to a lesser degree
      sadness, persist with an abstinence of 2 months and beyond. Right frontotemporal
      regions and cingulate could be implicated. These deficits may contribute to the
      social skills deficits frequently encountered in alcoholic patients.

PMID- 11513233
TI  - Pressure dependence of ionic polarizabilities in crystals.
AB  - A program in Maple V is developed that allows for the calculation of
      polarizabilities of both anions and cations on the basis of a new method and of
      the extension of the one developed previously. Furthermore, an alternative way of
      evaluation of delta r(i)/delta p is given. Values of delta alpha(total)/delta p
      can be evaluated for a given salt even when experimental data at high pressures
      are not available.

PMID- 11513234
TI  - Correlations between theoretical and experimental determination of heat of
      formation of certain aliphatic nitro compounds.
AB  - Heats of formation of energetic materials were calculated by Dewar's AM1 and
      Stewart's PM3 methods. In order to compare the theoretical results with the
      experimental ones, some correlation models were proposed in this study.
      Correlations were evaluated by multivariable linear regression method,
      considering the number of nitro groups and the use of quadratic relations
      involving the number of carbon, hydrogen, nitrogen, and oxygen atoms. Results
      indicated very precise correlations. Based on these correlations, heats of
      formation of some aliphatic nitro compounds can be predicted at 95% predictive
      interval without experimental analysis.

PMID- 11513235
TI  - Experimental study of precipitating systems; computerised analysis of the optical
      transmittance and associated noise.
AB  - The change of the transmittance in a precipitant system has been measured by
      using a focused laser beam into a precipitation cell in which the precipitate was
      generated by an injection technique. We have monitored the evolution of the
      transmittance on several precipitation processes with different chemicals (PbI2,
      PbSO4, BaSO4 and BaC2O4) and quantities of precipitated mass (20.0, 17.5, 15.0,
      12.5 and 10.0 mg). The noise associated to the transmittance signal has been
      obtained by a numerical procedure based on computer analysis, finding that it
      provides information about particle shape features and nucleation kinetics.

PMID- 11513236
TI  - Resolution by polarographic techniques of the ternary mixture of captan, captafol
      and folpet by using PLS calibration and artificial neuronal networks.
AB  - The simultaneous polarographic determination of the ternary mixture of captan
      captafol and folpet is studied. The polarographic signals of these compounds in
      their mixture show a high overlapping. For this reason different chemometric
      methods such as PLS, PCR and artificial neuronal network (ANN) have been utilized
      for the simultaneous determination of these compounds in mixtures. The
      calibration model is built from solutions containing river water of known
      pesticide concentrations and the signals obtained by Sampled DC and DPP
      (differential pulse polarography) have been used. The analysis of both synthetic
      and real samples (river water) has been carried out by PLS with satisfactory
      results in most cases. It is possible to determine 0.25 ppm of each pesticide in
      river water samples after a preconcentration step by extraction into diethyl
      ether. ANN has also been applied to improve the results obtained by the PLS tool
      when the sampled DC current is recorded or when liquid-solid extraction with C18
      cartridges is performed.

PMID- 11513237
TI  - Prediction of enthalpy of alkanes by the use of radial basis function neural
      networks.
AB  - A new method for the prediction of enthalpy of alkanes between C6 and C10 from
      molecular structures has been proposed. Thirty five calculated descriptors were
      selected for the description of molecular structures. The first four scores of
      Principle Component Analysis on the calculated descriptors were used as inputs to
      predict the enthalpy of alkanes. Models relating relationships between molecular
      structure descriptors and enthalpy of alkanes were constructed by means of radial
      basis function neural networks. To get the best prediction results, some
      strategies were also employed to optimise the learning parameters of the radial
      basis function neural networks. For the test set, a predictive correlation
      coefficient of R = 0.9913 and root mean squared error of 0.5876 were obtained.

PMID- 11513238
TI  - A new numerical procedure to determine the VLE curve.
AB  - A fast and accurate (to any required precision) numerical method is presented to
      calculate the vapour-liquid equilibrium for any subcritical temperature from a
      given equation of state. The calculations are made using the popular program
      MATHEMATICA, and we think that this method could be very useful in chemical
      physics and chemical engineering applications, as well as for teaching purposes.

PMID- 11513239
TI  - Three-dimensional quantitative structure-activity relationship for several
      bioactive peptides searched by a convex hull-comparative molecular field analysis
      approach.
AB  - Three-dimensional (3D) convex hulls are computed for theoretically generated
      structures of a group of 18 bioactive tachykinin peptides. The number of peptides
      treated as a training set is 14, whereas that treated as a test set is four. The
      frequency of atoms of the same atomic type lying at the vertices of all the hulls
      computed for all the structures in a structural set is counted. Vertex atoms with
      non-zero frequency counted are collected together as a set of commonly exposed
      groups. These commonly exposed atoms are then treated as a set of correspondences
      for aligning all the other 13 structures in a structural set against a common
      template, which is the structure of the most potent peptide in the set using the
      FIT module of the SYBYL 6.6 program. Each aligned structural set is then analyzed
      by the comparative molecular field analysis (CoMFA) module using the C.3 probe
      having a charge of +1.0. The corresponding cross-validated r2 values range from 
      0.99 to 0.57 for a number of 73 structural sets studied. The comparative
      molecular similarity indices analysis (CoMSIA) module within the SYBYL 6.6
      package is also used to analyze some of these aligned structural sets. Although
      the CoMSIA results are in accord with those of CoMFA, it is also found that the
      CoMFA results of several structural sets can be improved somewhat for
      conformations of the structures in the sets that are adjusted by constraint
      energy minimization and then constraint molecular dynamics simulation runs using
      distance constraints derived from some commonly exposed groups determined for
      them. This result further implies that the convex hull-CoMFA is a feasible
      approach to screen the bioactive conformations for molecules of this class.

PMID- 11513240
TI  - Study of precipitant systems by computerised simulation. Influence of optical
      elements on the noise associated with the transmittance.
AB  - The transmittance signal of a precipitant system measured with a focused laser
      beam carries associated noise coming from several sources. In this work, we have
      studied the influence of the focal parameters (wavelength, focal length and
      prefocused radius of the beam) on the maximum noise reached in equivalent
      nucleation processes. For this purpose, a simulation program of precipitating
      systems, designed in FORTRAN 90, has been developed. The program generates
      simulated transmittances, which are processed by another computer program to
      extract associated noise. Wide ranges of values of the focal parameters have been
      analysed, finding relationships between the maximum noise and the focal
      parameters. They have been justified in connection with the changes observed in
      the radial parameters, which define the size and shape of the focused path.

PMID- 11513241
TI  - High order spatial discretisations in electrochemical digital simulation. 2.
      Combination with the extrapolation algorithm.
AB  - The application of fourth order discretisations of the second derivative of
      concentration with respect to distance from the electrode, in electrochemical
      digital simulations, is examined. In the bulk of the diffusion space, a central
      five-point scheme is used, and six-point asymmetric schemes are used at the
      edges. In this paper, the scheme is applied to the extrapolation technique, based
      on the backward implicit (BI) algorithm for temporal integration, which (with
      extrapolation) allows higher orders in time as well. The method is found to be
      stable, using both the von Neumann and matrix methods. Exceptional efficiency is
      obtained both for Cottrell and chronopotentiometry simulations, requiring as few
      as 3-5 steps in time, starting at the dimensionless time t = 0 to gain four
      decimal accuracy at t = 1.

PMID- 11513242
TI  - Functional relationship among medial prefrontal cortex, nucleus accumbens, and
      ventral tegmental area in locomotion and reward.
AB  - Prominent projections of the medial prefrontal cortex (mPFC) to the nucleus
      accumbens (NAS) and the ventral tegmental area (VTA) exist, but it has been
      difficult to assign a clear functional role to either of these projections. With
      some exceptions to be discussed in some detail, only a few neurochemical and
      behavioral effects of manipulating the mPFC can be explained by invoking the mPFC
      NAS projection, while most effects are compatible with an involvement of the mPFC
      VTA-NAS or mPFC-pedunculopontine tegmental nucleus (PPTg)-VTA-NAS circuits. What
      is known about the organization and function of these loops is generally
      consistent with the results obtained by stimulating or lesioning or injecting
      drugs into the mPFC, yet these findings are largely inconsistent with the
      functional organization of the mPFC-NAS projection. This review briefly
      summarizes some of the most important aspects of what is known about the
      functional interactions of the mPFC. NAS, VTA, and associated areas, and focuses
      on functional differences between the mesocortical and the mesoaccumbal
      dopaminergic projections, and between the corticomesencephalic and the
      corticoaccumbal glutamatergic projections.

PMID- 11513243
TI  - Applications of microdialysis methodology in nonhuman primates: practice and
      rationale.
AB  - This review provides a comprehensive summary of the use of microdialysis
      procedures in nonhuman primates. Using these methods in primates is feasible,
      including both the anesthetized and awake preparations. The latter permit
      neurochemical sampling during complex information processing and behavioral
      performance. The close homology in structure and function between human and
      nonhuman primate brain makes using nonhuman primates particularly appealing, and
      the literature suggests that their use has provided instances of unique insight
      into brain structure and function. The continued use of these methods in areas
      such as the neurobiology of addiction, affective disorders, and psychosis will
      help in our ever-increasing understanding of the complex pathophysiologies of
      these disorders.

PMID- 11513244
TI  - Ca2+/calmodulin signaling in NMDA-induced synaptic plasticity.
AB  - Repeated experiences induce a synaptic plasticity in neurons that can be very
      long lasting. The neurotransmitter, glutamate, acting through N-methyl-D
      aspartate (NMDA) receptors is integrally involved in eliciting persistent changes
      in synaptic function resulting in learning and memory. The permeability of NMDA
      receptors to Ca2+ implies the close involvement of Ca2+ and the Ca2+-binding
      protein, calmodulin, in NMDA-induced synaptic plasticity. A notable example of
      NMDA-induced synaptic plasticity is long-term potentiation in the hippocampal CA1
      region. The involvement of Ca2+ and calmodulin in the induction and expression of
      LTP has been intensively investigated and documented. Less well studied are
      neurochemical adaptations in another example of NMDA-induced synaptic plasticity,
      stimulant-induced behavioral sensitization. Although amphetamine and cocaine
      increase synaptic monoamines, glutamate is involved in the induction and
      expression of the sensitization. Activating NMDA receptors in dopamine midbrain
      cell bodies is required for inducing stimulant sensitization, implying a role for
      Ca2+ in this plasticity. The purpose of this review is to examine the role of
      Ca2+ and calmodulin in two examples of NMDA-based plasticity, LTP, and stimulant
      induced behavioral sensitization. There are similarities in the neuroadaptations,
      although the role of Ca2+ and calmodulin has not been thoroughly investigated in
      the stimulant-induced plasticity.

PMID- 11513245
TI  - Disposition of naproxen, naproxen acyl glucuronide and its rearrangement isomers
      in the isolated perfused rat liver.
AB  - 1. An isolated perfused rat liver (IPRL) preparation was used to investigate
      separately the disposition of the non-steroidal anti-inflammatory drug (NSAID)
      naproxen (NAP), its reactive acyl glucuronide metabolite (NAG) and a mixture of
      NAG rearrangement isomers (isoNAG), each at 30 microg NAP equivalents ml
      perfusate (n = 4 each group). 2. Following administration to the IPRL, NAP was
      eliminated slowly in a log-linear manner with an apparent elimination half-life
      (t 1/2) of 13.4 +/- 4.4h. No metabolites were detected in perfusate, while NAG
      was the only metablolite present in bile in measurable amounts (3.9 +/- 0.8% of
      the dose). Following their administration to the IPRL, both NAG and isoNAG were
      rapidly hydrolysed (t 1/2 in perfusate = 57 +/- 3 and 75 +/- 14 min
      respectively). NAG also rearranged to isoNAG in the perfusate. Both NAG and
      isoNAG were excreted intact in bile (24.6 and 14.8% of the NAG and isoNAG doses,
      respectively). 3. Covalent NAP-protein adducts in the liver increased as the dose
      changed from NAP to NAG to isoNAG (0.20 to 0.34 to 0.48% of the doses,
      respectively). Similarly, formation of covalent NAP-protein adducts in perfusate
      were greater in isoNAG-dosed perfusions. The comparative results suggest that
      isoNAG is a better substrate for adduct formation with liver proteins than NAG.

PMID- 11513246
TI  - Carbamazepine: a 'blind' assessment of CVP-associated metabolism and interactions
      in human liver-derived in vitro systems.
AB  - 1. The ability of various in vitro systems for CYP enzymes (computer modelling,
      human liver microsomes, precision-cut liver slices, hepatocytes in culture,
      recombinant enzymes) to predict various aspects of in vivo metabolism and
      kinetics of carbamazepine (CBZ) was investigated. 2. The study was part of the
      EUROCYP project that aimed to evaluate relevant human in vitro systems to study
      drug metabolism. 3. CBZ was given to the participating laboratories without
      disclosing its chemical nature. 4. The most important enzyme (CYP3A4) and
      metabolic route (10,11-epoxidation) were predicted by all the systems studied. 5.
      Minor enzymes and routes were predicted to a different extent by various systems.
      6. Prediction of a clearance class, i.e. slow clearance, was correctly predicted
      by microsomes, slices, hepatocytes and recombinant enzymes (CYP3A4). 7. The 10,11
      epoxidation of CBZ by the recombinant CYP3A4 was enhanced by the addition of
      exogenous cytochrome-b5, leading to a considerable over-prediction. 8. Induction
      potency of CBZ was predicted in cultured hepatocytes in which 7-ethoxycoumarin O
      deethylase was used as an index activity. 9. It seems that for a principally CYP
      metabolized substance such as CBZ, all liver-derived systems provide useful
      information for prediction of metabolic routes, rates and interactions.

PMID- 11513247
TI  - Co-expression of human cytochrome P4501A1 (CYP1A1) variants and human NADPH
      cytochrome P450 reductase in the baculovirus/insect cell system.
AB  - 1. Three human cytochrome P4501A1 (CYP1A1) variants, wild-type (CYP1A1.1),
      CYP1A1.2 (1462V) and CYP1A1.4 (T461N), were co-expressed with human NADPH-P450
      reductase (OR) in Spodoptera frugiperda (Sf9) insect cells by baculovirus co
      infection to elaborate a suitable system for studying the role of CYPA1
      polymorphism in the metabolism of exogenous and endogenous substrates. 2. A wide
      range of conditions was examined to optimize co-expression with regard to such
      parameters as relative multiplicity of infection (MOI), time of harvest, haem
      precursor supplementation and post-translational stabilization. tinder optimized
      conditions, almost identical expression levels and molar OR/CYP1A1 ratios (20:1)
      were attained for all CYP1A1 variants. 3. Microsomes isolated from co-infected
      cells demonstrated ethoxyresorufin deethlylase activities (nmol/min(-1) nmol(-1)
      CYP1A1) of 16.0 (CYP1A1.1), 20.5 (CYP1A1.2) and 22.5 (CYP1A1.4). Pentoxyresorufin
      was dealkylated approximately 10-20 times slower with all enzyme variants. 4. All
      three CYP1A1 variants were active in metabolizing the precarcinogen
      benzo[a]pyrene (B[a]P), with wild-type enzyme showing the highest activity,
      followed by CYP1A1.4 (60%) and CYP1A1.2 (40%). Each variant produced all major
      metabolites including B[a]P-7,8-dihydrodiol, the precursor of the ultimate
      carcinogenic species. 5. These studies demonstrate that the baculovirus-mediated
      co-expression-by-co-infection approach all CYP1A1 variants yields functionally
      active enzyme systems with similar molar OR/CYP1A1 ratios, thus providing
      suitable preconditions to examine the metabolism of and environmental chemicals
      by the different CY1A1 variants.

PMID- 11513248
TI  - Disposition of propargyl alcohol in rat and mouse after intravenous, oral, dermal
      and inhalation exposure.
AB  - 1. The disposition of propargyl alcohol (PAL) radiolabelled with carbon-14 ([2,3
      14C]PAL) was determined in the F344 rat and B6C3F1 mouse following intravenous
      (i.v.), oral, inhalation and dermal exposure. 2. By 72h following an i.v. (1 mg
      kg(-1) or oral (50 mg kg(-1) dose, 76-90% of the dose was excreted. Major routes
      of excretion by rat were urine (50-62%), CO2 (19-26%) and faeces (6-14%). Major
      routes of exerection by mouse were urine (30-40%), CO2 (22-26%) and faeces (10
      20%). Less than 6% of the dose remained in tissues at 72 h. Biliary exeretion of
      radioactity by rat (62% in 4 h) was much greater than elimination in faeces (6%
      in 72 h), indicating that PAL metabolites underwent extensive enterohepatic
      recycling. 3. Dermal exposure studies demonstrated that dermal absorption of PAL
      was minimal due to its inherent volatility. 4. In the inhalation studies (1, 10
      or 100 ppm for 6 h), 23-68% of the radioactivity to which animals were exposed
      was absorbed. The primary route of excretion was urine (23-53%), and significant
      portion was exhaled as volatile organics (15-30%). 5. PAL was extensively
      metabolized by both species. One metabolite was identified as 3,3-bis[(2
      (acetylamino)-2-carboxyethyl)thio]-1-propanol, which is consistent with
      Banijamali et al. (1999).

PMID- 11513249
TI  - High-resolution magic angle spinning 1H-NMR spectroscopy studies on the renal
      biochemistry in the bank vole (Clethrionomys glareolus) and the effects of
      arsenic (As3+) toxicity.
AB  - 1. High-resolution magic angle spinning (MAS) 1H-NMR spectroscopy was used to
      study renal metabolism and the toxicity of As3+, a common environmental
      contaminant, in the bank vole (Clethrionomys glareolus), a wild species of
      rodent. 2. Following a 14-day exposure to an environmentally relevant dose of
      As2O3 (28 mg kg(-1) feed), voles displayed tissue damage at autopsy. MAS 1H
      spectra indicated abnormal lipid profiles in these samples. 3. Tissue necrosis
      was also evident from measurements of the apparent diffusion coefficient of water
      in the intact tissue using MAS 1H diffusion-weighted spectroscopy, its first
      application to toxicology. 4. Comparison of renal tissue from the wood mouse
      (Apodemus sylvaticus) exposed to identical exposure levels of As3+ suggested that
      the bank vole is particularly vulnerable to As3+ toxicity.

PMID- 11513250
TI  - Present and future of veterinary viral vaccinology: a review.
AB  - This review deals briefly with some key developments in veterinary vaccinology,
      lists the types of vaccines that are used for vaccinations commonly performed in
      food animals as well as in companion animals, and indicates that the practising
      veterinarian can select the best vaccine by comparing the results of efficacy
      studies. Diva (Differentiating Infected from Vaccinated Animals; also termed
      marker) vaccines and companion diagnostic tests have been developed that can be
      used for progammes aimed to control or eradicate virus infections. Vaccine
      induced herd immunity, which can be measured relatively easily when diva vaccines
      are used, is a crucial issue in such programmes. Current vaccine research follows
      many routes towards novel vaccines, which can be divided into non-replicating
      ('killed') and replicating ('live') vaccines. Promising trends are the
      development of DNA vaccination, vector vaccines, and attenuation of DNA and RNA
      viruses by DNA technology. The lack of (in vitro) correlates of vaccine
      protection markedly hampers progress in vaccine research. Various characteristics
      of an 'ideal' vaccine are listed, such as multivalency and the induction of
      lifelong immunity after one non-invasive administration in animals with maternal
      immunity. Future research should be aimed at developing vaccines that approach
      the ideal as closely as possible and which are directed against diseases not yet
      controlled by vaccination and against newly emerging diseases.

PMID- 11513251
TI  - Short-and long-term evaluation of surgical treatment of strangulating
      obstructions of the small intestine in horses: a review of 224 cases.
AB  - A retrospective study was carried out of 224 horses operated for strangulating
      small intestine obstructions. Fifty-four horses were euthanized and 5 horses died
      during surgery which means that 165 (73%) were allowed to recover. Of these, 53
      horses were euthanized or died in the clinic and 112 (50%) were discharged from
      the hospital. Of 90 horses available for follow-up 1 year postoperatively, 76
      (84%) were still alive. The most important causes of death or reasons for
      euthanasia in the direct post-operative period were post-operative paralytic
      ileus, (adhesive) peritonitis and intra-abdominal haemorrhage. After discharge
      from the hospital the reasons were (adhesive) peritonitis and (recurrent) colic.
      Of the horses which survived for at least 1 year, 16% sometimes suffered from
      colic, 12% experienced problems with incisional woundhealing and 4% suffered from
      jugular vein thrombosis. All were in good or reasonable condition and 88%
      performed at (approximately) the same level as before the operation. The type of
      surgical intervention (i.e. enterotomy, enterectomy) did not significantly
      influence the outcome of surgery, whereas the type of anastomosis did. End-to-end
      jejunojejunostomy had a better prognosis than side-to-side jejunocaecostomy. It
      was concluded that strangulating obstructions of the small intestine still carry
      a poor to guarded prognosis. Mortality was highest in the direct peri-operative
      period. Once discharged from hospital, prognosis can be considered to be fair to
      good. Attempts to improve outcome should be directed at a better handling of the
      ileal stump during surgery and at the prevention of post-operative ileus and the
      formation of adhesions.

PMID- 11513252
TI  - A longitudinal study of Salmonella enterica infections in high-and low
      seroprevalence finishing swine herds in The Netherlands.
AB  - The purpose of this investigation was to study the incidence and course of
      Salmonella infections in finishing pig herds in order to asses the stability of a
      given Salmonella herd status. Five low- and 7 high-seroprevalence herds were
      followed for seven sampling rounds. Each round, blood and faecal samples were
      tested in an indirect ELISA and by bacteriological culturing, respectively. In
      high-seroprevalence herds a positive Salmonella status was an indication of a
      long-term problem and the status was relatively stable over time. The herds
      experiencing clinical salmonellosis were not necessarily the herds with the
      highest seroprevalence. It is possible to deliver sero-negative finishers to the
      slaughterhouse, even though these pigs were seropositive as growers. In three out
      of five low-prevalence herds, major infection incidents occurred, indicating that
      changes in the Salmonella status should be anticipated. Low-prevalence herds can
      remain negative over a longer period of time as a result feeding a complete
      liquid feed containing fermented by-products.

PMID- 11513253
TI  - Administration of acidified drinking water to finishing pigs in order to prevent
      Salmonella infections.
AB  - The aim of the study was to test whether acidified drinking water, with two
      millilitres of an acid mixture per litre, was able to reduce the number of
      Salmonella infections in finishing pig herds. In each compartment, half of the
      pens were supplied with acidified water and the other pens served as negative
      control. In three herds the required dose was not applied to the pigs as a result
      of various practical problems. In another herd, all pigs remained seronegative
      throughout the study. Analysis of the remaining three herds showed a large and
      significant treatment effect in one herd (P<0.001). As a result of the small
      number of observations and the overall lower seroprevalence in the control
      groups, the other two herds only showed a statistical trend to a treatment effect
      (0.10<P<0.05). The main practical problem was the clogging of drinking nipples as
      a result of fungal growth in the pipelines.

PMID- 11513254
TI  - Heritability of plasma von Willebrand factor antigen concentration in German
      Wirehaired pointers.
AB  - We applied quantitative genetic analyses to a population of German Wirehaired
      pointer dogs affected with type 2 von Willebrand disease. Plasma von Willebrand
      factor (vWF) protein concentration measured as vWF antigen (vWF:Ag), clinical
      history, and pedigree data were compiled for 331 dogs over a 5-year test period.
      Eight dogs had histories of abnormal bleeding and had markedly decreased plasma
      vWF:Ag concentrations (<1%). Four per cent of the dogs were inbred, with an
      average inbreeding of 2.52%. The estimated heritability of plasma vWF
      concentration was 0.52. We found a major gene effect on vWF concentration. Using
      a single gene locus model and two different prediction methods, the upper
      threshold value for the aa genotype was less than 1% vWF:Ag, and the optimal
      threshold value for discrimination between the AA and Aa genotypes was between
      68% and 72% vWF:Ag. Our analyses indicate that phenotype, assigned on the basis
      of a single vWF:Ag determination, is heritable and can be applied for selective
      breeding in a von Willebrand disease test programme.

PMID- 11513255
TI  - Isolation of a new serotype of avian reovirus associated with malabsorption
      syndrome in chickens.
AB  - This paper describes the isolation and identification of a novel class of
      reoviruses, the so-called enteric reovirus strains (ERS). The pathogenicity,
      dissemination, induction of malabsorption syndrome (MAS), reaction pattern with
      different monoclonal antibodies, and serotype properties are reported. Upon
      screening of reoviruses in the field, it was observed that these reovirus strains
      were also present in other countries and were usually isolated from birds with
      MAS. Based on the data presented here, it is proposed that the so-called ERS are
      associated with MAS.

PMID- 11513256
TI  - Active surveillance of BSE in cattle in The Netherlands.
AB  - Since January 2, 2001 a large-scale active surveillance programme for BSE started
      in the Netherlands in addition to the passive surveillance programme of cattle
      with clinical symptoms compatible with BSE. Based on decisions of the Council of
      European Ministers of Agriculture, the European Union launched an active
      surveillance system for BSE in cattle of 30 months and older. Until April 1, more
      than 100,000 head of cattle were tested in this scheme, including all cattle
      slaughtered and a large part of the cattle that died on the farm. Four animals
      were found positive in the active surveillance system and one cow from the
      passive surveillance tested positive for BSE during the first three months.

PMID- 11513257
TI  - Antimicrobial resistance, pre-harvest food safety and veterinary responsibility.

PMID- 11513258
TI  - First report of a parasitic mite, Leptotrombidium (Hypotrombidium) subquadratum
      (Lawerence) (Acari: Trombiculidae: Trombiculinae), from dogs and children in the
      Bloemfontein area, South Africa.
AB  - Leptotrombidium subqunadratum larvae were collected for the first time in 1994
      from dogs in Bloemfontein. The larvae have been collected annually, during the
      summer months, over a period of 6-7 years. Previously the only known hosts were
      scrub hare (Lepus saxatilis) (locality unknown) and short-snouted elephant shrew
      (Elephantulus brachyrhynchus) (Kruger National Park). These mites cause severe
      itching and dermatitis in humans and dogs.

PMID- 11513259
TI  - Prevalence of Culicoides imicola and other species (Diptera: Ceratopogonidae) at
      eight sites in Zimbabwe.

PMID- 11513260
TI  - Chlamydial abortion in goats in the Umzimkulu district of Eastern Cape.

PMID- 11513261
TI  - The reversal of xylazine hydrochloride by yohimbine and 4-aminopyridine in goats.
AB  - Yohimbine, 4-aminopyridine, and a combination of the 2 drugs were studied to
      assess their potential as antagonists to xylazine in goats. Twenty-four small
      East African goats were divided randomly into 4 groups of 6 goats each in a
      placebo-controlled study. They were all treated with intramuscular xylazine at
      0.44 mg/kg. At the time of maximum sedation, sterile water was administered
      intravenously to the control group, 0.15% 4-aminopyridine at 0.4mg/kg to Group 2,
      0.1% yohimbine at 0.25 mg/kg to Group 3, and the combination of the 2 drugs at
      the same dose rates to Group 4. The yohimbine/4-aminopyridine combination was
      also used to antagonise xylazine at 0.88mg/kg in 6 goats. The heart rate,
      respiratory rate and rate of ruminal movements, the pedal and palpebral reflexes
      as well as the reaction to noxious stimuli, the standing time and the total
      recovery time were established and evaluated to assess the effects of the
      treatments. The drugs reversed the xylazine-induced decrease in the heart rate,
      respiratory rate and rate of ruminal movements, and also rapidly restored the
      reflexes as well as the reaction to noxious stimulation. In addition, they
      significantly (P < 0.05) decreased the mean standing time. The mean total
      recovery time was decreased significantly (P < 0.05) by 4-aminopyridine and the
      yohimbine/4-aminopyridine combination, but non-significantly (P > 0.05) by
      yohimbine. No relapse in sedation occurred. Overall, the combination of yohimbine
      and 4-aminopyridine produced better responses than the individual drugs, and may
      therefore be used for rapid reversal of xylazine-induced sedation in goats.
      Yohimbine or 4-aminopyridine may also be useful for this purpose but recovery may
      be prolonged.

PMID- 11513262
TI  - Lumpy skin disease in southern Africa: a review of the disease and aspects of
      control.
AB  - This article reviews some of the important aspects of lumpy skin disease (LSD)
      that may impact on its successful control. A resurgence of the disease in the
      last decade has highlighted some constraints of the Neethling strain vaccine, but
      there is no evidence of vaccine breakdowns owing to the presence of heterologous
      field strains. More research is needed on epidemiology and transmission of LSD in
      South Africa to formulate control measures.

PMID- 11513263
TI  - Birth of live calves by in vitro embryo production of slaughtered cows in a
      commercial herd in South Africa.
AB  - In vitro fertilisation (IVF) has become a useful breeding tool in most of the
      developed world. In this paper the success of bovine IVF and the birth of live
      calves under typical South African conditions is reported. Oocytes for IVF were
      collected from the ovaries of 6 slaughtered Bovelder beef cows. On average, 36.2
      oocytes per donor were retrieved. From these oocytes, 43 blastocysts were
      produced from 5 of the donors by IVF with frozen Bovelder semen. The best 11 of
      these embryos were transferred into oestrous, synchronised Bovelder recipients in
      the same herd. As a result, 7 calves were born (a 64% calving rate) from 4 of the
      original donors. The calves had a normal birth mass, but the mean gestation
      length of the male calves was significantly longer than the herd average (291.6
      versus 285.2 days respectively). No calving difficulties were encountered. In
      summary, it was shown that IVF for bovine embryo production and transfer is
      possible on a commercial basis in South Africa.

PMID- 11513264
TI  - Effects of anionic salts in a pre-partum dairy ration on calcium metabolism.
AB  - The effects of anionic salts in the transition diet on serum and urine calcium at
      calving and on peripartal health, subsequent milk production and fertility
      performance were studied in a well-managed, high-producing Friesland dairy herd.
      Over a period of a year, approximately 21 days before the expected date of
      calving, 28 pre-partum heifers and 44 multiparous dry cows were randomly
      allocated within parity to 1 of 2 transition diets, designated control and
      experimental anionic diets. The anionic diet contained the same quantities of the
      basic transition ration fed to the control group as well as a standard anionic
      salt mixture containing 118 g NH4Cl, 36 g (NH4)2SO4 and 68 g MgSO4 (total 222 g)
      per animal per day. This reduced the DCAD to -11.68 mEq/100 g dietary dry matter
      compared to +13.57 for the control diet. Blood and urine were randomly sampled
      from 7 to 8 animals within each category within 3 hours post-partum. Serum
      calcium (total and ionised) and creatinine, urine calcium and creatinine and the
      fractional clearance of calcium were assessed. Relevant clinical, milk
      production, and fertility data were collected. The total serum calcium (2.07
      versus 1.60 mmol/l), serum ionised calcium (1.12 vs 1.02 mmol/l), urine calcium
      (0.92 vs 0.10 mmol/l) and the fractional clearance of calcium (1.88 vs 0.09%)
      were significantly higher(P <0.01) at calving for multiparous cows fed the
      anionic diet compared to those fed the control diet. In the primiparous cows
      there were no significant differences in serum calcium levels. However, the urine
      calcium (1.07 vs 0.43 mmol/l) and the fractional clearance of calcium was higher
      (1.75 vs 0.45%) in cows fed the anionic diet (P <0.05 and 0.01 respectively).
      These results illustrated that there were benefits, although no differences were
      demonstrated with respect to health, milk production or fertility. The
      supplementation of diets with anionic salts in the last 2-3 weeks before calving
      has the potential to significantly improve parturient calcium homeostasis.

PMID- 11513265
TI  - Anaesthesia of gemsbok (Oryx gazella) with a combination of A3080, medetomidine
      and ketamine.
AB  - An effective anaesthesia protocol was developed for adult free-ranging gemsbok
      (Oryx gazella) using a combination of A3080, medetomidine and ketamine. A short
      induction time; good muscle relaxation, adequate oxygenation and stable heart
      rate and respiration rate characterised this anaesthetic regime. Equal doses of
      A3080 and medetomidine (22-45 microg/kg) plus 200 mg of ketamine were
      administered to each animal. The anaesthesia was rapidly and completely reversed
      by intramuscular naltrexone at a dose of X = 0.9 +/- 0.2 mg/kg and atipamezole at
      a dose X +/- 90 +/- 20 microg/kg. No mortality or morbidity occurred with this
      protocol.

PMID- 11513266
TI  - Analgesic and cardiopulmonary effects of intrathecally administered romifidine or
      romifidine and ketamine in goats (Capra hircus).
AB  - The study was conducted to evaluate the effects of romifidine alone (50
      microg/kg) and a combination of romifidine (50 microg/kg) and ketamine (2.5
      mg/kg) after intrathecal administration in goats. Ten adult goats of either sex
      weighing between 15 and 20 kg were randomly placed in 2 groups (groups I and II).
      The agents were administered at the lumbosacral subarachnoid space. Clinico
      physiological parameters such as analgesia, motor incoordination, sedation,
      salivation, heart rate, respiratory rate, arterial pressure, central venous
      pressure and rectal temperature were studied. Other haematobiochemical parameters
      monitored were packed cell volume, haemoglobin, plasma proteins, glucose, urea
      and creatinine. The onset of analgesia was faster in group II (35.5 +/- 6.25 s)
      compared to that of group I (5.2 +/- 0.54 min). Analgesia of the tail, perineum,
      hind limbs, flank and thorax was mild to moderate in group I, but complete
      analgesia of tail, perineum and hind limbs was recorded in group II. Motor
      incoordination was mild in group I and severe in group II. Significant reduction
      in heart rate (more pronounced in group I) and respiratory rate (more pronounced
      in group II), and a significant increase in central venous pressure were recorded
      in both groups. Mean arterial pressure was reduced in both groups, but more
      markedly in group I. Sedation, electrocardiogram, rectal temperature and haemato
      biochemical parameters did not show significant differences between the 2 groups.
      The results of this study indicated a possible synergistic analgesic interaction
      between intrathecally administered romifidine and ketamine, without causing any
      marked systemic effects in goats.

PMID- 11513267
TI  - Report of isolations of unusual lyssaviruses (rabies and Mokola virus) identified
      retrospectively from Zimbabwe.
AB  - Rabies isolates that had been stored between 1983 and 1997 were examined with a
      panel of anti-lyssavirus nucleocapsid monoclonal antibodies. Out of 56 isolates
      from cats and various wild carnivore species, 1 isolate of Mokola virus and 5
      other non-typical rabies viruses were identified. The Mokola virus isolate was
      diagnosed as rabies in 1993 from a cat. Genetic analysis of this isolate suggests
      that it falls in a distinct subgroup of the Mokola virus genotype. The 5 non
      typical rabies viruses were isolated from honey badgers (Mellivora capensis),
      African civets (Civettictis civetta) and an unidentified mongoose (Herpestidae).
      These isolates are representatives of rarely-reported wildlife-associated strains
      of rabies, probably maintained by the slender mongoose (Galerella sanguinea).
      These findings indicate that both Mokola virus and the mongoose-associated
      variant may be more common in Zimbabwe than is apparent from routine
      surveillance.

PMID- 11513269
TI  - Suspected post-vaccinal acute polyradiculoneuritis in a puppy.
AB  - A 4-month-old German shepherd puppy developed hindquarter weakness after
      vaccination with a multivalent vaccine. This is suggestive of post-vaccinal
      polyradiculoneuritis. To date, only 1 similar case has been reported, which may
      be due to the under-reporting of suspected adverse drug reactions.

PMID- 11513268
TI  - Isolation of Haemophilus somnus from dairy cattle in kwaZulu-Natal. An emerging
      cause of 'dirty cow syndrome' and infertility?
AB  - Haemophilus somnus was consistently isolated from vaginal discharges of dairy
      cows submitted from field cases of vaginitis, cervicitis and/or metritis in the
      KwaZulu-Natal Midlands during the period July 1995 - December 2000 and from the
      East Griqualand area in November/December 2000. The purulent vaginal discharges,
      red granular vaginitis and cervicitis, and pain on palpation described in these
      cases was very similar to that reported in outbreaks of H.somnus endometritis
      syndrome in Australia, Europe and North America. In all the herds involved in
      these outbreaks, natural breeding with bulls was employed. Although there was a
      good cure rate in clinically-affected animals treated with tetracyclines, culling
      rates for chronic infertility were unacceptably high. Employment of artificial
      insemination in these herds improved pregnancy rates in cows that had calved
      previously, but many cows that had formerly been infected failed to conceive.

PMID- 11513270
TI  - Prevalence of microorganisms associated with udder infections in dairy goats on
      small-scale farms in Kenya.
AB  - Six hundred and thirty clinically-normal milk samples from dairy goat flocks
      comprising a mixed population of German Alpine, Toggenburg, Saanen and Galla
      crosses were examined over a 3-month period to determine the prevalence of
      bacterial organisms. Bacteria were isolated in 28.7% of the milk samples
      (181/630) either singly (92.8%) or in combination (7.2%). The most prevalent
      bacterial organisms were Staphylococcus spp. (60.3%), followed by Micrococcus
      spp. (17.7%), Acinetobacter spp. (5%), Actinomyces spp. (5%) and Streptococcus
      spp. (1.1%). The Staphylococcus spp. were mainly coagulase negative (64.3%).
      Coagulase-negative staphylococci and coagulase-positive staphylococci accounted
      for 37.5% and 22.7% respectively of the total bacteria isolated. The isolation of
      bacteria, some of which are important in clinical and subclinical mastitis, in
      apparently normal caprine milk, indicates that particular attention should be
      given to the management of these dairy goat flocks in order to avoid the
      development of cases of clinical mastitis.

PMID- 11513271
TI  - Temporary remission of disseminated paecilomycosis in a German shepherd dog
      treated with ketoconazole.
AB  - Disseminated mycosis caused by Paecilomyces varioti in a female German shepherd
      dog presented with chronic forelimb lameness is described. Radiographs of the
      swollen carpal joint revealed geographic lysis of the radial epiphysis. Diagnosis
      was based on cytological demonstration of fungal hyphae and chlamydiospores, as
      well as fungal culture of fluid obtained by arthrocentesis. Temporary remission
      was characterised by markedly improved clinical signs and laboratory parameters,
      following treatment with ketoconazole. The dog was euthanased 9 months after the
      initial diagnosis, following the diagnosis of multifocal discospondylitis. This
      appears to be the longest described period of temporary remission obtained with
      treatment in dogs with paecilomycosis. Clinical, clinicopathological and necropsy
      findings of this disease in another German shepherd dog are briefly described.

PMID- 11513272
TI  - Comparative studies of gas chromatographic properties of new packings with
      chemically bonded complexes.
AB  - Specific interactions of aliphatic linear and branched hydrocarbons as well as
      cyclic and aromatic hydrocarbons with new packings containing chemically bonded
      complexes of transition metals are studied. The possibility of using these
      packings to separate these compounds is also discussed. The packings under study
      contain complexes of Cu(II) and Cr(III) chemically bonded to the silica surface.
      Chlorides of these metals are bonded to the silica surface by the use of the
      ketoimine group originally from 2-(3-triethoxysililpropylimino)-3-(n-buthyl)
      pentanon-4. In order to determine an influence of the performed modification to
      gas chromatographic properties of the packings, such retention parameters as
      retention factor, retention index, molecular retention index, and specific
      retention volume are measured for these compounds. Based on the obtained values,
      a trial is taken to determine an influence of the nature of the bonded metal from
      the complex on the retention of the adsorbates under study and a dependence
      between a structure of an adsorbate molecule and values of charge-transfer
      interactions with the bonded metal complexes.

PMID- 11513273
TI  - Analysis of wine for penicillin.
AB  - This study addresses the question of whether the antibiotic Penicillin, which is
      produced by the common mold Penicillium notatum, could possibly become a
      contaminate of wine during the fermentation process. The significance of this
      study is related to the potential health effects this agent might produce in
      those consumers who have an allergic response to Penicillin. It has been
      estimated that between 6% and 8% of the American population is subject to this
      type of allergic response. A method is developed for the detection of penicillin
      in wines using high-pressure liquid chromatography. We demonstrate that
      penicillin G hydrolyzes rapidly in wine with first-order kinetics, and the half
      life of this antibiotic is 147 min in a typical commercial wine. An analysis of a
      number of commercial wines shows no evidence of the presence of penicillin, which
      should negate the question of any allergic response associated with this
      potential contaminate.

PMID- 11513274
TI  - Comparison of extraction methods to monitor pesticide residues in surface water.
AB  - A regular monitoring program to study the pesticide concentration in surface
      waters has been carried out since 1976 in Hungary by the National Plant
      Protection Organization of the Ministry of Agriculture and Regional Development
      jointly with the Regional Water Authorities. At the beginning of this program a
      liquid-liquid partition method is used to extract the pesticides from water
      samples. After checking the pH value, one sample aliquot is extracted to analyze
      the basic and neutral compounds. Another aliquot is acidified to pH 2 and
      extracted to analyze acidic compounds. Disadvantages of this method are high
      solvent consumption and the need to apply solvents (methylene chloride and
      diethyl ether) that are harmful to human health. Therefore, the solid-phase
      extraction method has been introduced. This method has another advantage in that
      by using the vacuum manifold a number of samples can be extracted simultaneously
      depending on the capacity (number of ports) of the manifold. Three types of
      cartridges (LiChrolut EN, ISOLUTE ENV+, and Carbograph) are tested. The
      suitability and reproducibility of the extraction on various cartridges is
      studied and compared through recovery experiments. Recoveries are done for 22
      active ingredients at spiking levels of 1-5 times the limit of determination (in
      the range of 0.05-2.5 microg/L) with each extraction method. Individual recovery
      values as well as average recoveries for all methods are between 70% and 100%,
      with the relative standard deviation generally below 20%. Carbograph is the only
      cartridge among those studied that can be used to extract both neutral and acidic
      compounds in one sample loading step using two different consecutive elution
      steps.

PMID- 11513275
TI  - Separation of xylidine isomers by micellar electrokinetic chromatography.
AB  - Xylidines are important precursors for the production of dyes, drugs, and various
      other products. Because of the high carcinogenic nature of some xylidine isomers
      it becomes very essential and relevant to develop suitable analytical procedures
      to separate isomers as well as enhance detection at very low concentrations.
      Micellar electrokinetic chromatography has been standardized at various
      influencing parameters such as pH, ionic strength, and micelle modifiers, and the
      optimum conditions have been ascertained for the best separation and sensitivity
      of standard mixtures. The applicability of the procedure in environmental samples
      is studied.

PMID- 11513276
TI  - A simplex-optimized chromatographic separation of fourteen cosmetic
      preservatives: analysis of commercial products.
AB  - An ion-interaction high-performance liquid chromatography (HPLC)-diode-array
      detection method is developed and optimized for the separation of typical
      antimicrobial agents used in cosmetics and hygiene products. The most used
      preservatives contain different molecular structures, different functionalities,
      and are characterized by different chemical properties. Organic acids, alkyl
      esters of benzoic acids, alkyl p-hydroxy benzoic acids (parabens), phenol
      derivatives, and carbanilides represent the most used preservatives, and are
      often present in multicomponent mixtures. In order to develop a multicomponent
      method to be used in quality control analysis, the ion-interaction reagent
      reversed-phase HPLC technique seems to be particularly suitable, because it
      allows for the simultaneous separation of acidic, basic, and neutral species. The
      experimental conditions of the method are developed by OVAT (one variable at a
      time) treatment and further optimized by a multivariate approach based on a
      Simplex algorithm that works on a desirability function targeted to maximize the
      resolution in a multicomponent mixture. The new method proposed that is able to
      simultaneously separate fourteen preservatives is applied in the analysis of
      commercial products.

PMID- 11513277
TI  - Gas chromatographic method for assessing the dermal exposure of greenhouse
      applicators to dimethoate and malathion.
AB  - An analytical method is developed to determine potential and actual dermal
      exposure to dimethoate and malathion for agricultural workers using whole body
      dosimetry. The methodology described includes three different aspects: the
      validation of the analytical method incorporating a matrix effect for
      establishing performance parameters such as recovery rates (between 92% and 103%
      for both pesticides), limits of detection and quantitation, and precision of
      measurements (RSD < 10%); a field sampling strategy developing a procedure for
      collecting samples and carrying out field spikes and field blanks in order to
      ensure the stability of samples during transport, storage, and analysis; and
      finally, a quality control procedure for ensuring that data are under statistical
      control. The method is applied to evaluate the potential and actual dermal
      exposure as well as its distribution for a pesticide applicator and the
      applicator's assistant after a greenhouse application. Operator exposure levels
      of approximately 68 mL/h, and 25 mL/h in the case of the assistant, are found.
      The body areas most exposed are the lower body and hands.

PMID- 11513278
TI  - Multiresidue analysis of fluoroquinolone antibiotics in chicken tissue using
      automated microdialysis-liquid chromatography.
AB  - An efficient procedure for the simultaneous extraction and analysis of six
      fluoroquinolone (FQ) antibiotics is developed using an automated microdialysis
      liquid chromatographic (LC) system. In this method, samples extracted from
      chicken liver and muscle are further purified by microdialysis, separated on an
      LC column, and the FQs detected by their fluorescence. Recoveries from fortified
      chicken liver and muscle samples are at least 70% with limits of quantitation
      (microg/kg) for the FQs in liver (and muscle) as follows: 0.3 (0.4) for
      danofloxacin, 0.8 (0.2) for desethylene ciprofloxacin, 2 (1) for norfloxacin, 2
      (0.8) for enrofloxacin, 3 (1) for ciprofloxacin, and 5 (2) for sarafloxacin.
      Enrofloxacin and ciprofloxacin are determined in enrofloxacin-incurred chicken
      liver and muscle samples using this method.

PMID- 11513279
TI  - Selecting an internal standard.

PMID- 11513280
TI  - Drug treatment of nonviral sexually transmitted diseases: specific issues in
      adolescents.
AB  - Sexually transmitted diseases (STDs) are common and happen more frequently in
      younger patients. These adolescents have unique risks of acquiring infection
      because of developing psychosocial skills, biological factors and sociocultural
      barriers. The clinician must be adept at identifying and modifying these risks
      through knowledge of the adolescent stages of development and biology, with good
      history and examination skills that make teens comfortable during their
      evaluation, and with patient education and treatment. Whereas patient compliance
      and partner notification can be problematic in any population, teenagers may be
      more prone not to follow through on these issues. While compliance may notbe as
      important as previously thought, there is a dearth of studies of patient
      compliance and STD treatment in adolescents. Guidelines for the treatment of STDs
      were published by the Centers for Disease Control and Prevention (CDC) in 1998
      and the Medical Society for the Study of Venereal Diseases in 1999. Most of the
      data obtained to formulate these guidelines were not necessarily adolescent
      specific and few studies, if any, have included adolescent patients since the CDC
      document was published. In the treatment of chlamydia, it appears that even with
      relative noncompliance with the 7-day regimen of doxycycline, it is as effective
      as single dose azithromycin. This has implications in cost control, important for
      centres with limited funds for treatment. While fluoroquinolone-resistant
      gonorrhoea has been reported for some time, the number of reports in the US is
      increasing, with a recent report of decreased susceptibility to azithromycin. As
      many studies have shown efficacy with single agent therapy with azithromycin in
      combined gonococcal and chlamydial infection, one must view these new resistance
      data with concern and give serious consideration to dual agent treatment,
      especially in the locale of the practitioner. Also, fluoroquinolone use is not
      advised in patients under the age of 18 years at present because of concerns of
      adverse effects on cartilage. While not much has changed from the 1998 guidelines
      for most of the other STDs, there seems to be a general trend in treating pelvic
      inflammatory disease (PID) on an outpatient basis if good follow-up is assured,
      even in the adolescent population. There is still debate on whether anaerobe
      coverage is needed in PID without tubo-ovarian abscess or other complications.
      One other update includes the use of daily metronidazole gel instead of twice
      daily usage in the treatment of bacterial vaginosis. With the lack of studies
      specific to adolescents, it is left up to the clinician to tailor the treatment
      of adolescents on the basis of current guidelines and patient preferences.

PMID- 11513281
TI  - Optimising the benefits of anthelmintic treatment in children.
AB  - Optimal use of anthelmintics in children is of major public health importance
      because the parasites involved probably infect over 2 billion persons, and most
      are especially common and debilitating in children. Well targeted drug delivery,
      particularly via community chemotherapy, can substantially decrease aggregate
      morbidity and mortality and also improve growth rates, physical fitness and
      activity, cognitive and school performance, and social well-being. The drugs
      discussed here include the benzimidazoles (albendazole, levamisole and
      mebendazole), pyrantel, praziquantel, oxamniquine, ivermectin, diethylcarbamazine
      and some traditional medicines. The parasitic infections discussed are hookworm,
      ascariasis, trichuriasis, strongyloidiasis, schistosomiasis and lymphatic
      filariasis; onchocerciasis and loiasis are also mentioned briefly. Dosage
      regimens and effectiveness, including combination treatment, are discussed.
      Mechanisms by which parasites may cause or aggravate malnutrition and retard
      development are shown, along with examples of nutritional and functional
      improvement at various ages due to antiparasitic treatment. Improvement in
      appetite is likely to be the single most important mechanism through which a
      variety of physiological improvements occur. We recommend community treatment of
      girls and women of childbearing age in areas with widespread hookworm and
      anaemia, because effective treatment can reduce the incidence of low birthweight,
      mortality in infancy and pregnancy, and stunted growth and morbidity in children
      and adults. Treatment of moderate-to-severe anaemia improves appetite, growth and
      cognitive and school performance in children, and also improves work and social
      capacity and productivity in children and adults. Since treatment for helminth
      infections may also decrease both the probability of contracting HIV infection
      and the rate of viral replication in those infected with both types of organisms,
      large-scale treatment and control of helminths and treatment of individual cases
      when diagnosed are now truly urgent.

PMID- 11513284
TI  - Principles of disaster management lesson. 12: structuring organizations.
AB  - This lesson discusses various structures for organizations that have functional
      roles in disaster responses, relief, and/or management activities. It
      distinguishes between pyramidal and matrix structures, and notes the advantages
      and disadvantages of each in relation to disasters. Span of control issues are
      dissected including the impact of the "P" factor on the performance of disaster
      managers and workers including its relationship to the coordination and control
      function. The development of a Table of Organization and how it relates to
      departmentalization within an organization also is provided.

PMID- 11513283
TI  - Assessment and management of pain in neonates.
AB  - Neonates are capable of experiencing pain from birth onwards. An impressive body
      of neuroanatomical, neurochemical and biobehavioural evidence, which has
      accumulated over the past 2 decades, supports this capability. This evidence
      mandates health professionals to attend to the prevention, elimination, or at the
      very least, control of pain for infants. This mandate is essential since pain is
      known to have both immediate and long term effects, especially if pain is
      untreated and is severe, prolonged or frequently experienced. Therefore, pain
      must be assessed frequently, not only to measure location, intensity and duration
      but also to determine the effectiveness of interventions implemented to control
      pain. An impressive array of measures for assessing acute pain in infants exists
      which incorporates valid pain indicators in this population. However, there is a
      need to develop new measures to assess chronic pain conditions and pain in
      infants in acute situations.

PMID- 11513285
TI  - Toxic trauma.
AB  - Hazardous materials (HAZMAT) carry many inherent dangers. Such materials are
      distributed widely in industrial and military sites. Toxic trauma (TT) denotes
      the complex of systemic and organ injury caused by toxic agents. Often, TT is
      associated with other injuries that also require the application of life-support
      techniques. Rapid onset of acute respiratory failure and consequent
      cardiovascular failure are of primary concern. Management of TT casualties is
      dependent upon the characteristics of the toxic agents involved and on the
      demographics surrounding the HAZMAT incident. Agents that can produce TT possess
      two pairs of salient characteristics: (1) causality (toxicity and latency), and
      (2) EMS system (persistency and transmissibility). Two characteristics of
      presentations are important: (1) incident presentation, and (2) casualty
      presentation. In addition, many of these agents complicate the processes
      associated with anaesthesia and must be dealt with. Failure of recognition of
      these factors may result in the development of respiratory distress syndromes and
      multiorgan system failure, or even death.

PMID- 11513286
TI  - Effects of the video case study in preparing paramedic preceptors for the role of
      evaluator.
AB  - INTRODUCTION: Accurate field evaluations are critical in determining paramedic
      students' competency to provide patient care. The [U.S.] National Paramedic
      Curriculum does not address the skills needed by evaluators, and requirements to
      be a preceptor/evaluator vary from state to state. Therefore, it is imperative
      that educational programs develop an evaluation process that reflects valid
      performance criteria and assure a high degree of rating consistency among the
      evaluators. This study sought to determine the effects of using a video case
      based teaching approach in preparing paramedic preceptors for the role of
      evaluator. HYPOTHESIS: Paramedic preceptors receiving the case-based teaching
      approach to prepare them for the role of evaluator would demonstrate
      significantly higher scores on a video posttest than paramedic preceptors who
      were not prepared for the role of evaluator using the case-based approach.
      METHODS: Thirty-four paramedic preceptors from a Midwestern fire-based EMS system
      were enrolled in this study. Two scripted video student/patient encounters were
      used to measure evaluation scores in a pretest-posttest comparison of control
      versus experimental group. The experimental group was given structured rating
      guidelines and practice applying those guidelines to a case study. Pretest and
      posttest scores were weighted and analyzed using ANOVA. RESULTS: Analysis of the
      pretest-posttest differences revealed significantly higher scores for the
      experimental group in the categories containing complex behaviors: communication
      F (1,16) = 13.21,p <.01, assessment F (1,16) = 8.81,p <.01, and knowledge F
      (1,16) = 29.64, p <.001. There was no significant difference between groups in
      the categories containing simple, easily observed behaviors: reliability F (1,16)
      = .55, p >.05 and cooperativeness F (1,16) = 3.02,p >.05. CONCLUSIONS: Using the
      case study method and written guidelines that provide concrete examples of
      complex behaviors appears to increase reliability of evaluations among
      preceptors.

PMID- 11513282
TI  - Drug therapy approaches in the treatment of acute severe asthma in hospitalised
      children.
AB  - Acute severe paediatric asthma remains a serious and debilitating disease
      throughout the world. The incidence and mortality from asthma continue to
      increase. Early, effective and aggressive outpatient therapy is essential in
      reducing symptoms and preventing life-threatening progression. When complications
      occur or when the disease progresses to incipient respiratory failure, these
      children need to be managed in a continuous care facility where aggressive and
      potentially dangerous interventions can be safely instituted to reverse
      persistent bronchospasm. The primary drugs for acute severe asthma include
      oxygen, corticosteroids, salbutamol (albuterol) and anticholinergics. Second-line
      drugs include heliox, magnesium sulfate, ketamine and inhalational anaesthetics.
      Future therapies may include furosemide, leukotriene modifiers, antihistamines
      and phosphodiesterase inhibitors. This review attempts to explore the multitude
      of medications available with emphasis on pharmacology and pathophysiology.

PMID- 11513287
TI  - Y2K medical disaster preparedness in New York City: confidence of emergency
      department directors in their ability to respond.
AB  - OBJECTIVES: To study the preparedness New York City for large scale medical
      disasters using the Year 2000 (Y2K) New Years Eve weekend as a model. METHODS:
      Surveys were sent to the directors of 51 of the 9-1-1-receiving hospitals in New
      York City before and after the Y2K weekend. Inquiries were made regarding
      hospital activities, contingencies, protocols, and confidence levels in the
      ability to manage critical incidents, including weapons of mass destruction (WMD)
      events. Additional information was collected from New York City governmental
      agencies regarding their coordination and preparedness. RESULTS: The pre-Y2K
      survey identified that 97.8% had contingencies for loss of essential services,
      87.0% instituted their disaster plan in advance, 90.0% utilized an Incident
      Command System, and 73.9% had a live, mock Y2K drill. Potential terrorism
      influenced Y2K preparedness in 84.8%. The post-Y2K survey indicated that the
      threat of terrorism influenced future preparedness in 73.3%; 73.3% had specific
      protocols for chemical; 62.2% for biological events; 51.1% were not or only
      slightly confident in their ability to manage any potential WMD incidents; and
      62.2% felt very or moderately confident in their ability to manage victims of a
      chemical event, but only 35.6% felt similarly about victims of a biological
      incident. Moreover, 80% felt there should be government standards for hospital
      preparedness for events involving WMD, and 84% felt there should be government
      standards for personal protective and DECON equipment. In addition, 82.2% would
      require a moderate to significant amount of funding to effect the standards.
      Citywide disaster management was coordinated through the Mayor's Office of
      Emergency Management. CONCLUSIONS: Although hospitals were on a heightened state
      of alert, emergency department directors were not confident in their ability to
      evaluate and manage victims of WMD incidents, especially biological exposures.
      The New York City experience is an example for the rest of the nation to
      underscore the need for further training and education of preparedness plans for
      WMD events. Federally supported education and training is available and is
      essential to improve the response to WMD threats.

PMID- 11513288
TI  - Emergency medical services assessment and treatment of children with special
      health care needs before and after specialized paramedic training.
AB  - INTRODUCTION: This study evaluates whether a continuing education program for
      paramedics, focusing on Children with Special Health Care Needs, improved
      paramedics' assessment and management. METHODS: Emergency Medical Services
      responses for children, 21 years of age or younger, with a congenital or acquired
      condition or a chronic physical or mental illness, were identified. The responses
      before and after the specialized education program were reviewed by a
      multidisciplinary team to evaluate assessment and management of the children.
      Interreviewer agreement between the nurses on the team and between the physicians
      on the team was assessed. We also evaluated whether there was an improvement in
      assessment and care by paramedics completing our education program. RESULTS:
      Significant improvement was seen in appropriate assessment and overall care by
      paramedics who completed our specialized education program. Reviewers also noted
      an appropriate rating for the initial assessment category more often for
      responses involving paramedics who had the training. Agreement on whether
      assessment and treatment was appropriate for all five reviewers varied
      considerably, ranging from 32% to 93%. Overall there was a high percentage of
      agreement (>70%) between the nurses and between the physicians on most items.
      However, kappa statistics did not generally reflect good agreement except for
      most of the focused assessment items and some treatment and procedure items.
      CONCLUSION: Most of the documentation on the EMS records indicated appropriate
      assessment and treatment during all responses for Children with Special Health
      Care Needs. Nevertheless, the results indicate that paramedics may improve their
      assessment and management of these children after specialized continuing
      education.

PMID- 11513289
TI  - The other chromatin.
AB  - Current understanding of heterochromatin, thanks to molecular data, focuses on
      its performing several functions in evolution and development. Heterochromatin
      shows characteristic distribution patterns in karyotypes and contributes to the
      broad scattering of genome sizes through biological taxa. Heterochromatin remains
      compacted and thus different from properly stained euchromatin during somatic
      interphase. A minimum amount of heterochromatin, however, is required for it to
      be visible in light microscopy. It may further escape notice during the dynamic
      processes of embryogenesis and gametogenesis. Present-day biology is in search of
      specific proteins and DNA sequences that comprise heterochromatin. The data that
      result from overcoming the threshold of visibility will support understanding of
      interference by heterochromatin in ontogeny and evolution. The contributions of
      Sigrid and Wolfgang Beermann to the study of heterochromation diminution (DNA
      elimination) are recalled, and we also discuss the functions and effects of
      heterochromatin on differential DNA endoreplication and in speciation.

PMID- 11513290
TI  - The evolutionary life history of P transposons: from horizontal invaders to
      domesticated neogenes.
AB  - P elements, a family of DNA transposons, are known as aggressive intruders into
      the hitherto uninfected gene pool of Drosophila melanogaster. Invading through
      horizontal transmission from an external source they managed to spread rapidly
      through natural populations within a few decades. Owing to their propensity for
      rapid propagation within genomes as well as within populations, they are
      considered as the classic example of selfish DNA, causing havoc in a genomic
      environment permissive for transpositional activity. Tracing the fate of P
      transposons on an evolutionary scale we describe different stages in their
      evolutionary life history. Starting from horizontal transfer events, which now
      appear to be rather a common phenomenon, the initial transpositional burst in the
      new host is slowed down by the accumulation of defective copies as well as host
      directed epigenetic silencing. This leads to the loss of mobility and, finally,
      to molecular erosion by random mutations. Possible escape routes from genomic
      extinction are the reactivation within the original host genome by recombination
      or suspension of the repressing regime, horizontal emigration to a virgin gene
      pool, or genomic integration and acquisition of a novel function as a
      domesticated host gene.

PMID- 11513291
TI  - The nuclear location and chromatin organization of active chorion amplification
      origins.
AB  - It remains unclear how certain regions on metazoan chromosomes are selected to
      initiate DNA replication. In recent years a number of origins of DNA replication
      have been mapped, but there is still no DNA consensus for predicting where
      replication will initiate. Evidence suggests that the higher order structure of
      the nucleus and chromosome influences origin activity. Chromosomal DNA
      replication is proposed to occur in special compartments in the nucleus called
      replication foci. Foci in different regions of the nucleus initiate replication
      at different times of S-phase, suggesting nuclear position may contribute to
      where and when replication begins. Here we test the contribution of nuclear
      compartments for well-defined origins, those involved in amplification of the
      chorion (eggshell) genes during Drosophila oogenesis. The results of three
      dimensional confocal microscopy indicate that chorion DNA replication origins are
      highly active in diverse positions within the nucleus. We also find that chorion
      replication origins inserted at ectopic chromosomal sites can amplify highly in
      diverse nuclear locations distinct from the endogenous loci, including when they
      are buffered against genomic position effects. We used fluorescence in situ
      hybridization to analyze chromosome structure during amplification. Contrary to
      the replication factory model, we find no evidence for spooling of DNA toward a
      replication center. We discuss the implications of these results for
      understanding the role of higher order structure in amplification and chromosome
      duplication.

PMID- 11513292
TI  - Packing and delivery of a genetic message.
AB  - Balbiani rings (BRs) 1 and 2 are two exceptionally large chromosomal puffs on
      chromosome IV in the salivary glands of the dipteran Chironomus tentans. The BR
      genes are 35-40 kb, contain four short introns, and encode salivary polypeptides
      of one million molecular weight. They have proven uniquely suited for
      visualization of the assembly and transport of a specific messenger
      ribonucleoprotein (RNP) particle. A BR transcript is packed with proteins into a
      thin RNP fibril, which is folded into a compact ring-like structure. The
      completed BR particle is released from the gene and moves randomly in the
      nucleoplasm before it becomes associated with the nuclear pore complex. The
      passage through the nuclear pore is a highly ordered process with a series of
      consecutive steps: initial binding, docking, unfolding, movement through the pore
      with the 5' end of the transcript in the lead, and exit into the cytoplasm. On
      the cytoplasmic side, the RNA becomes immediately engaged in protein synthesis.
      Recently, several major proteins in the BR particle have been identified and
      characterized. They are added to the BR RNA molecule concomitantly with
      transcription. During the ensuing RNA transport, the various proteins behave
      differently, some remaining in the nucleus, others entering the cytoplasm coupled
      to the RNA. The flow pattern of a given protein seems to be closely related to
      the specific function of the protein. The RNA-binding proteins are likely to play
      various active roles during gene expression rather than being solely packaging
      proteins. Finally, it is emphasized that the co-transcriptional loading of the
      transcript with proteins is probably a key process in gene expression that to a
      large extent determines the fate of an mRNA both in the nucleus and the
      cytoplasm.

PMID- 11513294
TI  - A heterochromatic satellite DNA is highly amplified in a single chromosome of
      Muscari (Hyacinthaceae).
AB  - We examined the composition and evolution of a large heterochromatic region
      present in the genomes of certain species of the genus Muscari (Hyacinthaceae).
      We found that in Muscari comosum this heterochromatic region is composed mainly
      of a satellite DNA family, which we named MCSAT. Molecular analyses and in situ
      hybridization revealed that, through the evolution of Muscari species, the MCSAT
      sequences have been progressively amplified in several species of the genus, such
      as M. matritensis and M. dionysicum, attaining enormous amplification in the
      genome of M. comosum. We discuss the characteristics of this satellite DNA
      family, which, being exclusively amplified in one chromosome pair of M. comosum,
      constitute the major exception to the equilocal model of satellite DNA and
      heterochromatin distribution. Also, we discuss the possibility that the
      amplification of these sequences in a single chromosome could have contributed to
      a progressive increase in the asymmetry of the karyotypes in Muscari species.

PMID- 11513293
TI  - Maintenance of the DNA puff expanded state is independent of active replication
      and transcription.
AB  - The maintenance of the expanded state of DNA puffs II/2B and II/9A in polytene
      chromosomes from stage 14 x 7 Sciara coprophila salivary glands was assayed after
      inhibition of RNA synthesis, DNA synthesis, or both processes together. Heat
      shock conditions were established in order to inhibit transcription. Polypeptides
      of Mr 72,000 and 36,000 were produced in Sciara after heat shock. The gene
      encoding the Mr 72,000 polypeptide, the homolog of Drosophila hsp70, was cloned.
      In situ hybridization detected Sciara hsp70 at bands 4A and 17C on chromosome IV.
      Sciara hsp70 encodes a 2.3 kb heat shock mRNA. DNA puffs (e.g., DNA puffs 2B and
      9A on chromosome II) remained fully expanded even after inhibition of
      transcription by heat shock or actinomycin D, or after inhibition of DNA
      replication by aphidicolin, or inhibition of both RNA synthesis and DNA synthesis
      together by actinomycin D plus aphidicolin. Therefore, maintenance of the DNA
      puff expanded state in Sciara does not require ongoing transcription and/or
      replication. Mechanisms for initiation and for maintenance of puffs (open
      chromatin structure) are discussed.

PMID- 11513295
TI  - Characterisation of pericentrometric and sticky intercalary heterochromatin in
      Ornithogalum longibracteatum (Hyacinthaceae).
AB  - The hexaploid liliaceous plant Ornithogalum longibracteatum (2n=6x=54) has a
      heterochromatin-rich bimodal karyotype with large (L) and small (S) chromosomes.
      The composition and subgenomic distribution of heterochromatin was studied using
      molecular and cytological methods. The major component of centromeric
      heterochromatin in all chromosomes is Satl, an abundant satellite DNA with a
      basic repeat unit of 155 bp and an average A+T content (54%). The major component
      of the large blocks of intercalary heterochromatin in L chromosomes is Sat2, an
      abundant satellite DNA with a basic repeat unit of 115 bp and a high A+T content
      (76%). Additionally, traces of Sat2 can be detected at the centromeric regions of
      S chromosomes, while minor amounts of Satl are discernible in intercalary
      heterochromatin of L chromosomes. The chromosomal localisation pattern of Sat2 is
      consistent with the fluorescent staining pattern obtained with the A+T-specific
      DNA ligand 4'-6-diamidino-2-phenylindole (DAPI). A+T-rich intercalary
      heterochromatin is sticky and tends to associate ectopically during mitosis.
      Sister chromatid exchange clustering was found at the junctions between
      euchromatin and heterochromatin and at the centromeres. The pattern of mitosis
      specific phosphorylation of histone H3 was not uniform along the length of the
      chromosomes. In all L and S chromosomes, from early prophase to ana-/telophase,
      there is hyperphosphorylation of histone H3 in the pericentromeric chromatin and
      a slightly elevated phosphorylated histone H3 level at the intercalary
      heterochromatin of L chromosomes. Consequently, the overall phosphorylated
      histone H3 metaphase labelling resembles the distribution of Satl in the
      karyotype of O. longibracteatum.

PMID- 11513296
TI  - Heterochromatin and interstitial telomeric DNA homology.
AB  - The purpose of this investigation was twofold. The first objective was to
      demonstrate that, in most of ten mammalian species commonly used in biomedical
      research, not all constitutive heterochromatin (C-bands) represents telomeric
      DNA. For example, the C-bands in human chromosomes, the long arm of the X and the
      entire Y chromosome of Chinese hamster, and most of the short arms of Peromyscus
      and Syrian hamster chromosomes are not telomeric DNA. In addition to the usual
      terminal telomeric DNA in the chromosomes of these mammalian species, the
      pericentromeric regions of seven or eight Syrian hamster chromosomes and all
      Chinese hamster chromosomes except pair one have pericentromeric regions that
      hybridize with telomeric DNA, some in C-bands and some not. The second objective
      was to describe a simple fluorescence in situ hybridization (FISH) reverse
      printing procedure to produce black-and-white microphotographs of metaphase and
      interphase cells showing locations of telomeric DNA with no loss of resolution.
      Thus, at least three different types of heterochromatin (telomeric
      heterochromatin, nontelomeric heterochromatin and a combination of both) are
      present in these mammalian species, and this simple black-and-white reverse
      printing of telomeric FISH preparations can depict them economically without
      sacrificing clarity.

PMID- 11513297
TI  - Telomeres in Chironomus thummi are characterized by different subfamilies of
      complex DNA repeats.
AB  - Members of the genus Chironomus, as well as other Diptera, lack the highly
      conserved structure of most telomeres, characterized by short repeats generated
      by telomerase, and have long repeats at their chromosome ends. Among Chironomus
      species with characterized telomeres Chironomus thummi is of particular interest
      because one of the telomeres, 3R, forms a giant puff in response to heat shock
      and other stress treatments. The puff contains nucleoprotein granules in which
      transcripts of the telomeric repeats are present. Most other nontelocentric
      telomeres irregularly form less pronounced heat shock puffs. One, the 4R telomere
      is, however, exceptional in being completely refractory to heat shock. We now
      pose the question whether the repeats in 3R and 4R have special sequence
      features. We find three different subfamilies of telomeric repeats in C. thummi,
      named TsA, TsB and TsC. They have an identical length (176 bp) and display base
      differences in defined regions, V1 and V2, connected by conserved segments. The
      TsA subfamily is localized exclusively at 3R, TsC only at 4R, whereas TsB repeats
      are shared by the remaining nontelocentric telomeres: 1R, 1L, 2R, 2L and 3L.
      Consequently both 3R and 4R have unique types of telomeric repeats. The 176 bp
      type repeats are absent from the telocentric, left end of chromosome 4. These
      results allowed us to differentiate in polytene chromosomes four types of
      telomeres characterized by tandemly repeated specific sequences.

PMID- 11513298
TI  - A role of the Drosophila homeless gene in repression of Stellate in male meiosis.
AB  - The homeless gene of Drosophila melanogaster encodes a member of the DE-H family
      of ATPase and RNA helicase proteins. Loss-of-function homeless mutations were
      previously found to cause female sterility with numerous defects in oogenesis,
      including improper formation of both the anterior-posterior and dorsal-ventral
      axes and failure to transport and localize key RNAs required for axis formation.
      One homeless mutation was also found to affect male meiosis, causing elevated X-Y
      nondisjunction. Here we further analyze the role of homeless in male meiosis. We
      show that homeless mutations cause a variety of defects in male meiosis including
      nondisjunction of the X-Y and 2-2 pair, Y chromosome marker loss, meiotic drive,
      chromosome fragmentation, chromatin bridges at anaphase, and tripolar meiosis. In
      addition, homeless mutations interact with an X chromosomal factor to cause
      complete male sterility. These phenotypes are similar to those caused by deletion
      of the Suppressor of Stellate [Su(Ste)] locus. Like Su(Ste) deficiencies,
      homeless mutants also exhibit crystals in primary spermatocytes and derepression
      of the X-linked Stellate locus. To determine whether the regulatory role of hls
      is specific for Stellate or includes other repeated sequences as well, we
      compared testis RNA levels for nine transposable elements and found that all but
      one, copia, were expressed at the same levels in hls mutants and wild type.
      Copia, however, was strongly derepressed in hls mutant males. We conclude that
      hls functions along with Su(Ste) and other recently described genes to repress
      the Stellate locus in spermatocytes, and that it may also play a role in
      repressing certain other repeated sequences.

PMID- 11513299
TI  - Molecular phylogenetics of howler monkeys (Alouatta, Platyrrhini). A comparison
      with karyotypic data.
AB  - Molecular phylogenetic analyses of seven Brazilian Alouatta species, based on
      cytochrome b DNA sequence data were carried out. Parsimony and neighbor joining
      topologies grouped Alouatta belzebul and A. fusca as sister groups in one clade
      while another, well-supported clade contained A. seniculus as the most basal
      offshoot, followed by A. nigerrima as a sister lineage of A. macconnelli/A.
      stramineus. Estimates of inter-specific sequence divergence were generally low,
      and estimates of the time of divergence indicated that the main Alouatta lineages
      emerged during a short evolutionary interval. A comparison with karyotypic data
      confirmed the molecular topology showing a closer relationship between A.
      macconnelli and A. stramineus in respect to A. nigerrima. It also showed that the
      XX/XY sex chromosome system was maintained in several lineages while the
      X1X2Y/X1X1X2X2 system appeared independently at least three times during the
      radiation of howler monkeys. Moreover, the X1X2Y1Y2/X1X1X2X2 system might have
      appeared once or, alternatively, twice and independently.

PMID- 11513300
TI  - Relationship between functional deficit and severity of experimental fast-strain
      injury of rat skeletal muscle.
AB  - We developed a rat model of fast-strain muscle injury to examine the relationship
      between functional deficit and the degree of muscle damage. A single fast strain
      was applied to the right plantaris (Plt) muscle of adult male rats. A tetanic
      contraction was induced by stimulating the sciatic nerve. Three types of strain
      injuries were produced by manipulating the timing of strain and contraction
      conditions, including applying the strain at: (1) the shortening phase (SP), (2)
      the full contraction phase (FCP) during tetanic contraction and (3) when the
      muscle is not contracting, i.e. non-contraction (NC). The contralateral Plt
      muscle was used as the control. Morphological and functional analysis were
      performed and the severity of strain injury was estimated by measuring
      [3H]thymidine labelling 48 h after the strain was applied. The results show a
      significant decrease in tension output in all three groups at 5 min after strain
      application (P < 0.01). The functional deficit lasted for 3 weeks in the NC
      group, while rats of the SP and FCP groups showed recovery 1 week after strain.
      Increased uptake of [3H]thymidine was similar in SP and FCP groups, but 3.5-fold
      higher in NC than in SP and FCP groups (P < 0.01). Histological analysis revealed
      an increase in the size of interstitial spaces of the muscle in NC compared to SP
      and FCP groups (P<0.05). Our results suggest that the contraction of muscle
      fibres limits the severity of connective tissue damage, and that muscle damage
      accompanied by disruption of the muscle connective tissue network requires a
      relatively longer recovery time.

PMID- 11513301
TI  - Age-related differences in postural control in humans in response to a sudden
      deceleration generated by postural disturbance.
AB  - Age-related differences in postural control in response to a relatively large
      deceleration resulting from postural disturbance were investigated in eight
      normal elderly men (age range 67-72 years) and eight young men as controls (age
      range 19-22 years) using a moving platform. Data were obtained for the hip, knee
      and ankle angles, position of the centre of foot pressure (CFP), head
      acceleration, and muscle activity of the leg muscles. The elderly subjects had
      slower and larger ankle and hip joint movements, and CFP displacement in response
      to the disturbance compared to the young controls. The elderly subjects also had
      a delayed occurrence, and greater magnitude of peak acceleration of head rotation
      than did the young subjects. For the elderly subjects, the CFP was closely
      related to angular changes in the hip joint movement, but not to those of the
      ankle and knee joint movements. For the young subjects, on the other hand, the
      CFP was significantly correlated with angular change in the ankle joint.
      Cocontraction of the tibialis anterior and gastrocnemius muscles was observed in
      the elderly subjects. The results indicated that a movement pattern for postural
      correction in the elderly adults was different from that of the young adults. The
      elderly relied more on hip movements while the young controls relied on ankle
      movements to control postural stability.

PMID- 11513302
TI  - Blood lipids of young distance runners: distribution and inter-relationships
      among training volume, peak oxygen consumption, and body fatness.
AB  - This study describes the distribution of blood lipid concentrations and examines
      relationships among training volume (TV, kilometers per week), peak oxygen
      consumption (VO2peak), body fatness, and blood lipid concentrations in 48 male
      and 22 female distance runners, aged 10-19 years. Comparisons were made to a
      current reference sample and clinical cut-off points. Relationships were assessed
      by partial correlations allowing for age and sexual maturity. Compared to
      reference median values, mean concentrations of total cholesterol (P=0.07) and
      low density lipoprotein-cholesterol (P<0.005) were higher, while high density
      lipoprotein-cholesterol (HDL-C; P=0.24) was comparable in male distance runners.
      Blood lipid concentrations in female distance runners were comparable to
      reference median values. Although some subjects had dyslipidemic values, most
      possessed clinically normal concentrations of blood lipids. The TV was weakly
      correlated with blood lipid concentrations, but may have been indirectly related
      with HDL-C through its relationship with VO2peak in males runners (r=0.32). In
      female runners, correlations between sum of skinfolds (SSF), the trunk-to
      extremity ratio (TER) and blood lipid concentrations were low (r=0.16 to -0.27),
      with one exception (TER and HDL-C, r=-0.60). The most consistent relationships
      existed among TV, VO2peak, SSF, and HDL-C with partial correlations ranging from
      low (r=0.10 TV) to moderate (r=0.37 SSF, r=0.41 VO2peak). The correlation between
      VO2peak and HDL-C remained significant after allowing for age and SSF, while the
      partial correlation between SSF and HDL-C, allowing for age and VO2peak, was
      reduced and not significant (r=-0.19, P=0.20). In female runners, the correlation
      between VO2peak and HDL-C was r=0.32, whereas the partial correlation between SSF
      and HDLC, allowing for age and VO2peak, was r=0.00. Blood lipid concentrations of
      young male distance runners were not, on average, different to the general
      population of the youth of the United States. The young distance runners showed
      considerable heterogeneity in blood lipid phenotypes, including dyslipidemic
      values. The results highlight the complex relationships among TV, VO2peak, body
      fat and HDL-C, and indicate the unique contribution of VO2peak as an important
      predictor of HDL-C in young distance runners.

PMID- 11513303
TI  - Effects of high-altitude exposure on vascular endothelial growth factor levels in
      man.
AB  - Vascular endothelial growth factor (VEGF) is an endothelial cell mitogen and
      permeability factor that is inducible by hypoxia. Its contribution to high
      altitude illness in man is unknown. We measured VEGF levels in 14 mountaineers at
      low altitude (490 m) and 24 h after their arrival at high altitude (4,559 m). At
      high altitude, VEGF increased from [mean (SEM)] 32.5 (9.2) to 60.9 (18.5) pg.ml(
      1) (P < 0.004) in the arterial blood, and from 15.9 (2.9) to 49.3 (15.9) pg.ml(
      1) (P= 0.0001) in the mixed venous blood. Whereas at low altitude venous and
      arterial VEGF levels were not statistically different from each other (P= 0.065),
      the VEGF concentration was significantly lower in venous than in arterial blood
      samples at high altitude (P=0.004). The pulmonary capillary VEGF concentration
      remained unchanged at high altitude [14.8 (2.5) vs 17.1 (5.4) pg.ml(-1), P=0.85].
      VEGF levels in the nine mountaineers who developed symptoms of acute mountain
      sickness (AMS), and in the six subjects who had radiographic evidence of high
      altitude pulmonary edema were similar to those in subjects without symptoms. VEGF
      was not correlated with either AMS scores, mean pulmonary arterial pressures,
      arterial partial pressure of O2, or alveolar-arterial O2 gradients. We conclude
      that VEGF release is stimulated at high altitude, but that VEGF is probably not
      related to high-altitude illness.

PMID- 11513304
TI  - Left ventricular contractile performance in the early stage of hypertension in
      humans.
AB  - The aim of the present study was to assess how cardiac structural changes
      contribute to increasing left ventricular pump function during exercise in
      subjects with mild hypertension. In 23 young male subjects with mild hypertension
      and 12 male normotensive control subjects, left ventricular function was measured
      echocardiographically using the fractional shortening/ meridional stress
      relationship at rest and during longlasting exercise at the anaerobic threshold.
      Mean exercise duration and intensity were 61 (SEM 1.7) min and 71.3 (SEM 2.5)%
      VO2max (maximal oxygen uptake), respectively, in the hypertensive subjects, and
      63 (SEM 1.5) min and 75.7 (SEM 2.2)% VO2max, respectively, in the normotensive
      subjects (all differences= n.s.). Left ventricular fractional shortening was
      measured both at the endocardium and at the midwall. In the hypertensive subjects
      the endocardial fractional shortening, predicted on the basis of the
      shortening/stress relationship in the normotensive controls, overestimated
      midwall fractional shortening throughout rest (P=0.04) and exercise (P=0.004). To
      study how an increase in left ventricular wall thickness contributed to
      increasing ejection performance during exercise, the hypertensive subjects were
      divided according to whether their relative wall thickness was less than 0.35 or
      equal to or greater than 0.35. Subjects with relative wall thicknesses equal to
      or greater than 0.35 had a depressed myocardial contractility at rest (P=0.0001).
      During exercise they increased their stroke volume and cardiac output adequately
      through an increase in ejection performance, while myocardial contractility
      remained subnormal (P < 0.0001). In conclusion, the present results indicated
      that in mildly hypertensive subjects an increased left ventricular wall thickness
      is crucial in preserving left ventricular pump function during exercise.

PMID- 11513305
TI  - Effects of ambient cold and depth on lung function in humans after a single scuba
      dive.
AB  - This study evaluated the subacute respiratory effects of diving, to try to
      separate the effects of ambient temperature from those of depth. In the first
      experiment 10 healthy men made a compressed-air dive to 50 m that exposed them to
      cold. They were compared with 10 matched control subjects who underwent the same
      dive profile but were exposed to a comfortable temperature. In the second
      experiment 16 healthy subjects made randomized cold dives to both 50 m and 10 m.
      Pulmonary function tests were made before, after 1 h, and 24 h after the dives.
      In the first experiment there was an increase in residual volume (P < 0.05) and a
      decrease in forced expiratory volume at 1 s (FEV1), in forced vital capacity
      (FVC) and in mid-expiratory flow at 75% of FVC (MEF75) 1 h after the cold dives
      (P < 0.05). In the second experiment significant increases in specific airways
      resistance (sR(AW)) (P < 0.05) and decreases in FEV1 (P<0.01), in MEF75 (P<0.05),
      and in mid-expiratory flow at 25% of FVC (P<0.05), were obtained after the 50 m
      dives, whereas SR(AW) increased after the 10 m-dives (P<0.05). The respiratory
      pattern observed 1 h after cold dives to 50 m indicated airway narrowing. The
      changes after cold dives to 10 m, however, were of minor magnitude. Both cold and
      depth seemed to contribute to the adverse effects of a single compressed-air dive
      on pulmonary function.

PMID- 11513306
TI  - Electrical characteristics of human ankle dorsi- and plantar-flexor muscles.
      Comparative responses during fatiguing stimulation and recovery.
AB  - Changes in muscle excitability were investigated during fatigue and the recovery
      of human dorsi- and plantar-flexor isometric contractions. The indirectly evoked
      muscle compound action potentials [tibialis anterior (TA) and soleus (SOL) M
      waves] were used as an index of excitability. Ten subjects successfully completed
      five experiments, spaced at least 1 week apart, in which intermittent tetanic
      trains at different frequencies of stimulation (0-30 Hz) were used to fatigue the
      ankle dorsi-flexors. Muscles were rendered ischaemic via a thigh cuff inflated
      above mean arterial pressure. The effects of ischaemia were examined by repeating
      the 20-Hz stimulation protocol under non-ischaemic conditions. Five of those
      subjects also participated in one further session in which the ischaemic plantar
      flexors were also fatigued. It was hypothesized that muscle excitability would be
      preferentially retained in the SOL. Maintenance of excitability in both muscles
      was possible for 1 min regardless of stimulus frequency; thereafter, stimulation
      at the highest frequencies induced the greatest decline [30 Hz stimulation; 95.4
      (0.5)%, P < 0.01) in the amplitude of the M-wave. The decline in M-wave amplitude
      was always greater than the decline in M-wave area and occurred at firing rates
      not normally associated with neuromuscular blockade, implying propagation failure
      along the sarcolemma. The presence of ischaemia significantly accelerated the
      decline in both amplitude (78% versus 12%, P<0.01) and area (45% versus no
      decline, P<0.01) of the M-wave. Recovery was limited when tetanic stimulation
      ceased but progressed rapidly after circulation was restored. Twitch and tetanic
      torque declines were significantly different between SOL and TA (fall between
      rest and fatigue -SOL: 77%, 75.2%; TA: 95.5%, 96.9%, P<0.01, respectively). M
      wave changes between the two muscles were not significantly different although
      the onset of the decline was delayed in the SOL. It is proposed that the observed
      delay in fatiguing decline was due to the early potentiation in muscle
      excitability observed in the SOL but not in the TA.

PMID- 11513307
TI  - Use of a cold cathode for percutaneous stimulation of human plantarflexor
      muscles.
AB  - Prolonged, supramaximal stimulation of the soleus muscle is painful to humans. A
      method is proposed whereby percutaneous, supramaximal stimulation is possible
      using a cold cathode. Cooling the skin exposed to the stimulating current results
      in a sufficient anaesthesia of nociceptive cutaneous afferent nerves. This occurs
      without concomitant cooling of the muscle mass deep to the skin and subcutaneous
      tissue.

PMID- 11513308
TI  - Resynchronization of hormonal rhythms after an eastbound flight in humans:
      effects of slow-release caffeine and melatonin.
AB  - The aim of this work was to investigate the potential chronobiotic properties of
      slow-release caffeine, in comparison with melatonin, on resynchronization of
      endogenous melatonin and cortisol secretions after an eastbound flight by jet
      incurring a time loss of 7 h. A group of 27 reservists of the US Air Force
      received either slow-release caffeine (300 mg), melatonin (5 mg) or placebo
      before, during and/or after the transmeridian flight. Saliva and urine were
      sampled before the flight in the United States (from day -2 to day 0) and after
      the flight in France (from day 1 to day 10). Saliva was collected once a day on
      waking to determine saliva melatonin and cortisol concentrations. In addition,
      concentrations of caffeine in saliva were determined three times a day and of 6
      sulphatoxymelatonin in urine collected overnight to check that the treatment
      regimes had been complied with. From day 3 to day 5, post-flight saliva melatonin
      concentrations were significantly different from control values in the placebo
      group only. During treatment with melatonin, the mean urinary 6
      sulphatoxymelatonin concentration in the melatonin group was more than twice as
      high as in the two other groups. In the slow-release caffeine group and the
      melatonin group, mean saliva cortisol concentrations were significantly lower
      than control from day 2 to day 5, whereas the placebo group had a mean saliva
      cortisol concentration significantly lower than the control value from day 2 to
      day 9. In conclusion, these results indicate that administration of slow-release
      caffeine, as well as of melatonin, allows a faster resynchronization of hormone
      rhythms during the 4 days following an eastbound flight incurring the loss of 7
      h.

PMID- 11513309
TI  - Exercise-induced changes in blood levels of alpha-tocopherol.
AB  - Levels of alpha-tocopherol (alphaT) in plasma and red blood cells (RBC) are
      assumed to be modulated by exercise. The mechanisms involved remain to be
      established. We examined the influence of different running bouts on the content
      of alphaT in RBC (alphaT(RBC)), the concentration in plasma (alphaTplasma), and
      their relationship with lipolysis, as indicated by changes (delta) in plasma
      glycerol concentration ([glycerol]). Eleven healthy runners [mean (SD) age 35 (9)
      years, height 177.3 (7.6) cm, body mass 69.6 (9.4) kg, and peak oxygen
      consumption, VO2peak, 57.8 (4.8) ml.kg(-1).min(-1)] performed an incremental
      treadmill test [duration 17 (2) min, peak velocity, vpeak 4.8 (0.4) m.s(-1)], a
      training run [173 (12) min, 57 (4)% vpeak] and a marathon [197 (24) min, 75 (5)%
      vpeak]. Before (pre) and after (post) each run, haematological and lipid
      parameters, alphaT(RBC) and alphaTplasma were determined. Haemoconcentration was
      observed after each run. delta[glycerol] was +0.10 (0.10) mmol.l(-1), +0.40
      (0.14) mmol.l(-1) and +0.51 (0.15) mmol.l(-1) in the treadmill test, training run
      and marathon, respectively. When corrected for haemoconcentration, values of
      alphaTplasma decreased [-5.4 (7.5)%, P< 0.05] in the treadmill test, were
      unchanged [+0.7 (8.7)%] in the training run and increased [+7.8 (8.3)%, P<0.05]
      in the marathon. alphaT(RBC) decreased [pre vs post: 22.7 (3.2) nmol.g
      haemoglobin(-1) (nmol.g Hb(-1)) vs 18.9 (3.8) nmolg Hb(-1), P < 0.05] in the
      treadmill test and was not significantly changed in either the training run [20.8
      (1.9) nmol.g Hb(-1) vs 19.1 (3.0) nmol.g Hb(-1)] or the marathon [21.6 (2.9)
      nmol.g Hb(-1) vs 23.4 (2.7) nmol.g Hb(-1)]. deltaalphaT(RBC) and
      deltaalphaTplasma were positively related to delta[glycerol]. The reduction in
      alphaTRBC and alphaTplasma after short-lasting heavy exercise indicates the
      consumption of alphaT, whereas the association between deltaalphaT and
      delta[glycerol] suggests mobilisation of alphaT, especially in long-lasting
      exercises. However, although alphaT appears to be influenced by exercise, the
      results suggest a well-balanced regulation of alphaT during exercise resulting in
      small, and only in part, significant deltaalphaT in blood.

PMID- 11513310
TI  - Concurrent improvements in cardiorespiratory and muscle fitness in response to
      total body recumbent stepping in humans.
AB  - A group of 26 sedentary adults [mean age 48.4 (SD 6.4) years] were allocated
      randomly into either a non-exercising control group (CON, n =9) or an exercise
      group (EX, n = 17) that trained 3 days a week for 12 weeks using a total body
      recumbent stepper (TBRS). Training intensity and duration progressed from 50% of
      heart rate reserve maximum (HRRmax) for 20 min to 75% HRRmax for 40 min. Maximal
      exercise responses were measured during incremental treadmill (TM) and TBRS tests
      to examine the specificity of the adaptations to training. Muscle strength was
      measured using a one repetition maximum (1 RM) test for the leg press (LP), chest
      press (CP), and seated row (SR). Muscle endurance (END) was evaluated for LP, CP,
      and SR as the number of repetitions achieved before failure when exercising at an
      intensity of 60% of baseline 1 RM. Body composition was estimated using the sum
      of seven skinfolds. After training, significant increases (P < 0.05) in maximal
      oxygen uptake and exercise time were observed in the EX group on both the TM
      (9.3% and 4.8%, respectively) and TBRS (18.2% and 70.5%, respectively). The TBRS
      training resulted in significant increases (P < 0.01) in 1 RM and END of the
      legs, chest, and back, with greater magnitude of improvements observed for END.
      Furthermore, TBRS training resulted in a significant increase in lean body mass
      and significant reductions in fat mass and percentage body fat (P<0.01). The CON
      did not show changes in any measurement (P>0.05). These data indicated concurrent
      improvements in both cardiovascular and muscle fitness. The greater improvements
      observed on the TBRS test and in muscle endurance suggest the adaptations are
      specific to the mode of training.

PMID- 11513311
TI  - Exercise training attenuates aging-associated increases in collagen and collagen
      crosslinking of the left but not the right ventricle in the rat.
AB  - The purpose of this study was to compare the independent and interactive effects
      of age and exercise training on selected parameters of the right ventricle (RV),
      left ventricular septum (LVS) and left ventricular free-wall (LVFW) extracellular
      matrix. Specifically, we evaluated collagen and collagen crosslinking
      (hydroxylysylpyridinoline, HP) concentrations in the myocardial extracellular
      matrix in young adult, Y (5.5 months) and old, O (25.5 months) male Fischer 344
      rats. Rats were assigned to either a sedentary control (YC, OC) or an exercise
      training group (YT, OT). Rats were trained for 45 min/day, 5 days/week, for 10
      weeks at approximately equals 70% of maximal oxygen consumption. Following the
      training regimen, rats were sacrificed and their hearts were dissected into the
      RV, LVS and LVFW. Training resulted in a significant hypertrophy of the left
      ventricle (LV) but not RV relative to body weight. In young rats, collagen
      concentration was significantly higher (P<0.01) in RV compared to LVS, but not
      LVFW. With aging, collagen concentration increased significantly (P<0.05) in both
      ventricles, but more so in LV than RV so that differences in percent collagen
      observed between chambers in both YC and YT rats no longer existed in OC and OT
      animals. This aging effect was attenuated by training in the LVS but not the
      LVFW, so that collagen concentration, while higher in this region of the LV in OT
      compared to YT rats, was also lower than that seen in the LVS of OC rats. HP
      crosslink concentration in the LVS and LVFW, but not the RV of OC rats was
      significantly elevated above corresponding values seen in YC rats (P < 0.05 or
      greater). In YT rats, training had no effect on HP crosslinking concentration in
      any of the three regions of the heart. However, in OT rats, training completely
      prevented the age-associated increase in crosslinking seen in both the LVS and
      LVFW of OC animals. These findings illustrate the different responses of the RV,
      LVS and LVFW extracellular matrix components, collagen and HP crosslinking, to
      both aging and training in the rodent.

PMID- 11513312
TI  - In vivo muscle mechanics during locomotion depend on movement amplitude and
      contraction intensity.
AB  - The effects of movement amplitude and contraction intensity on triceps surae and
      quadriceps femoris muscle function were studied during repetitive hopping. In
      vivo forces from Achilles and patellar tendons were recorded with the optic fibre
      technique from eight volunteers. The performances were filmed (200 Hz) to
      determine changes in muscle-tendon unit length and velocity. When hopping with a
      small amplitude (23 degrees knee flexion during the ground contact phase), the
      Achilles tendon was primarily loaded whereas patellar tendon forces were greater
      in large-amplitude hopping (56 degrees knee flexion). In spite of the different
      magnitudes of stretch in the quadriceps femoris muscle, the stretching velocity
      and activity patterns of the quadriceps muscle were similar in both conditions.
      Simultaneously performed electromyographic (EMG) recordings revealed that
      preferential preactivation of the gastrocnemius muscle was evident in both
      jumping conditions. The triceps surae muscle was strongly active in the eccentric
      phase of small-amplitude hopping. Results from hopping with small knee-joint
      displacement suggest that there may be a particular frequency and jumping height
      at which the elastic bouncing is best utilized and at the same time the
      concentric phase is most economical. Results also support earlier observations
      that the economy of the shortening phase must be compromised at some point in
      order to produce more power and improve the jumping height.

PMID- 11513313
TI  - Testosterone, dehydroepiandrosterone, insulin-like growth factor 1, and insulin
      in sedentary and physically trained aged men.
AB  - The influence of physical activity on dehydroepiandrosterone sulfate (DHEAS),
      total and free testosterone (TT and FT, respectively), insulin-like growth factor
      I (IGF-1), follicle-stimulating hormone (FSH), luteinizing hormone (LH) and
      insulin concentrations in aging men was investigated. Eight trained and nine
      sedentary men aged 60-65 years volunteered to participate in this study. Physical
      activity was determined during an effort test and evaluated by the measure of the
      maximal aerobic power (W(aer,max)). In the trained aging men, the W(aer,max) was
      higher than in the sedentary group of matching age [mean (SD) 206.8 (17.1) W
      versus 136.6 (12.3) W; P<0.0001]. The fat percentage was higher in the sedentary
      (n = 9) than in the trained (n = 8) group [23.9 (3.2)% versus 14.6 (3.7)%;
      P<0.0001]. DHEAS and IGF-1 levels were higher in trained than in sedentary
      subjects, respectively 2.04 (1) micromol/l versus 1.01 (0.68) micromol/l (P=0.02)
      and 192.1 (40.1) ng/ml versus 132.8 (31.2) ng/ml (P= 0.003). Insulin levels were
      higher in sedentary subjects [11.2 (3.5) mIU/l versus 7.6 (2.2) mIU/l, P=0.03].
      No statistical difference was observed between both groups for FT and total TT
      values, FSH values and LH values. IGF-1 was correlated with W(aer,max) (r = 0.64,
      P = 0.003), and DHEAS was correlated with IGF-1 (r=0.59, P=0.01). We observed a
      relationship between fat percentage and each of the following hormones: IGF-1 (r=
      0.50, P=0.03), FT (r=-0.66, P= 0.002), TT (r=-0.54, P = 0.02) and insulin
      (r=0.63, P=0.004). Insulin was inversely correlated with FT (r= -0.66, P=0.002)
      and TT (r=-0.47, P=0.05). These results suggest that regular physical activity
      could maintain higher DHEAS and IGF-1 and lean body mass levels in elderly men,
      and participate in general well being in older age.

PMID- 11513314
TI  - Biarticular and monoarticular muscle activation and injury in human quadriceps
      muscle.
AB  - We hypothesized that activation of the quadriceps femoris muscle group during
      eccentric exercise is related to the increase in magnitude of several markers of
      muscle injury that developed during the next week. Fourteen male subjects
      performed six to eight sets of five to ten repetitions of single-leg eccentric
      only seated knee extension exercise. Magnetic resonance (MR) images were
      collected before and immediately after exercise and on days 2-4 and 6 after
      eccentric exercise. Changes in maximal voluntary contraction (MVC), perceived
      soreness, muscle volume and muscle transverse relaxation of water protons (T2)
      were determined for the quadriceps femoris muscle group each day. Changes in
      muscle volume and T2 were determined every day for each muscle [vastus lateralis
      (VL), vastus medialis (VM), vastus intermedius (VI), rectus femoris (RF)] of the
      quadriceps femoris group. Post-exercise T2 was greater than pre-exercise T2 (P <
      0.05) for all muscles. The acute deltaT2 (Post-Pre) was similar (P>0.05) among
      VL, VM, VI, and RF [5.5 (0.3) ms], suggesting that the four muscles were equally
      activated during eccentric exercise. In the week after eccentric exercise,
      subjects experienced delayed-onset muscle soreness (DOMS) and all muscles
      demonstrated a delayed increase in T2 above pre-exercise values (P < 0.05),
      suggesting that muscle injury had occurred. For the quadriceps femoris muscle
      group, there was no correlation between acute deltaT2 and delayed (peak T2 during
      days 2, 3, 4, 6 minus pre-exercise T2) deltaT2 (r=0.04, P>0.05). Similar results
      were obtained when VL, VM, VI and RF were examined separately. Of the four
      muscles in quadriceps femoris, the biarticular RF experienced greater muscle
      injury [delayed deltaT2= 15.2 (2.0) ms] compared to the three monoarticular vasti
      muscles [delayed deltaT2 = 7.7 (1.3) ms; P< 0.05]. We propose that the
      disproportionate muscle injury to RF resulted from an ineffective transfer of
      torque from the knee to hip joint during seated eccentric knee extension
      exercise, thus causing RF to dissipate greater energy than normal. We conclude
      that in humans, muscle activation is not a unique determinant of muscle injury.

PMID- 11513315
TI  - The relationship between critical velocity, maximal lactate steady-state velocity
      and lactate turnpoint velocity in runners.
AB  - In cycle exercise, it has been suggested that critical power, maximal lactate
      steady state, and lactate turnpoint all demarcate the transition between the
      heavy exercise domain (in which blood lactate is elevated above resting values
      but remains stable over time) and the very heavy exercise domain (in which blood
      lactate increases continuously throughout constant-intensity exercise). The
      purpose of the present study was to assess the level of agreement between
      critical velocity (CV), maximal lactate steady-state velocity (MLSSV), and
      lactate turnpoint velocity (LTPV) during treadmill running. Eight male subjects
      [mean (SD) age 28 (5) years, body mass 71.2 (8.0) kg, maximum oxygen uptake 54.9
      (3.2) ml.kg(-1).min(-1)) performed an incremental treadmill test for the
      determination of LTPV (defined as a sudden and sustained increase in blood
      lactate concentration ([La]) at approximately equals 2.0-5.0 mM). The subjects
      returned to the laboratory on eight or nine occasions for the determination of CV
      and MLSSV. The CV was determined from four treadmill runs at velocities that were
      chosen to result in exhaustion within 2-12 min. The MLSSV was determined from
      four or five treadmill runs of up to 30 min duration and defined as the highest
      velocity at which blood [La] increased by no more than 1.0 mM after between 10
      and 30 min of exercise. Analysis of variance revealed no significant differences
      between [mean (SD)] CV [14.4 (1.1) km.h(-1)], MLSSV [13.8 (1.1) km.h(-1)] and
      LTPV [13.7 (0.6) km.h(-1)]. However, the bias +/-95% limits of agreement for
      comparisons between CV and MLSSV [0.6 (2.2) km.h(-1)], CV and LTPV [0.7 (2.7)
      km.h(-1)], and MLSSV and LTPV [0.1 (1.8) km.h(-1)] suggest that the extent of
      disagreement is too great to allow one variable to be estimated accurately from
      another in individual subjects. Direct determination of MLSSV is necessary if
      precision is required in experimental studies.

PMID- 11513316
TI  - Venous blood lactate increase after vertical jumping in volleyball athletes.
AB  - The aim of this study was to test the hypothesis that venous blood lactate
      concentrations ([La-]) would vary from the beginning of brief exercise. Maximal
      vertical jumping was used as a model of brief intense exercise. Eleven healthy
      male volleyball players, aged [mean (SE)] 18.5 (0.7) years, performed three
      exercise tests with different protocols, each separated by quiet seated recovery
      periods of 45 min. After the first test, consisting of a single maximal jump
      [lasting approximately equals 0.6 s for the pushing phase, and in which the
      subjects jumped 64 (2.2) cm], forearm venous [La-] increased significantly with
      respect to rest at 1 min (t1), 3 min (t3), and 5 min (t5) of recovery. The second
      test, comprising six maximal jumps, each separated by 20-s recovery periods,
      resulted in an unchanged [La-] with respect to the baseline value. After the
      third test [i.e., six consecutive maximal jumps that lasted a total of 7.36
      (0.33) s], [La-] increased significantly at t3 and t5 with respect to the pre
      test value (F= 10.3, P < 0.001). We conclude that a significant venous [La-]
      increase occurs after vertical jumping. This result may be explained by the
      activation of lactic anaerobic metabolism at the very onset of exercise, which
      participates in energy production and/or in the resynthesis of the
      phosphocreatine that was used during such brief exercise.

PMID- 11513317
TI  - Physiological responses in tennis and running with similar oxygen uptake.
AB  - The purpose of the study was to compare selected physiological responses during
      singles tennis match play and continuous running at a similar mean oxygen uptake
      (VO2). The study consisted of two main parts, which were separated by 1 week. In
      the first part, 12 nationally ranked senior tennis players [six females and six
      males; 47.2 (6.6) years old and 47.0 (5.4) years old, respectively] each
      completed a 2-h singles tennis match (TE). Mean VO2 during TE [23.1 (3.1) ml.kg(
      1). min(-1) for the women and 25.6 (2.8) ml.kg(-1).min(-1) for the men] was
      measured by a portable spirometry-telemetry system and corresponded to 56%
      (women) or 54% (men) of their respective maximum VO2. In the second part, the
      relative VO2 data measured during TE were used to set a similar workload during a
      2-h treadmill run at a constant level (RU). At the measured time points, heart
      rate [140.1 (15.5) beats.min(-1) vs 126.4 (15.1) beats. min(-1)], lactate
      concentration [1.53 (0.65) mmol.l(-1) vs 1.01 (0.38) mmol.l(-1)] and glucose
      concentration [5.45 (0.84) mmol.l(-1) vs 4.34 (0.56) mmol.l(-1)] in capillary
      blood, as well as the respiratory exchange ratio [0.93 (0.03) vs 0.88 (0.03)],
      were higher (P<0.05) in TE compared to RU. Serum concentrations of free fatty
      acids increased (P < 0.05) during both work loads [from 0.25 (0.15) mmol.l(-1) to
      1.31 (0.44) mmol.l(-1) in TE and from 0.22 (0.17) mmol.l(-1) to 1.24 (0.35)
      mmol.l(-1) in RU]. Post-exercise urine concentrations of epinephrine [0.17 (0.14)
      micromol.l(-1) vs 0.08 (0.04) micromol.l(-1)] and norepinephrine [1.27 (0.59)
      micromol.l(-1) vs. 0.55 (0.33) micromol.l(-1)] were higher in TE (P<0.05). These
      results indicate a stronger metabolic emphasis on glycolysis and glycogenolysis
      and an overall enhanced sympathoadrenal activity during tennis match play
      compared to continuous running exercise at a similar mean VO2.

PMID- 11513318
TI  - The repeated bout effect of reduced-load eccentric exercise on elbow flexor
      muscle damage.
AB  - In this study we investigated the extent to which an initial eccentric exercise
      consisting of two (2ECC) or six maximal eccentric actions (6ECC) of the elbow
      flexors would produce a similar effect to 24 maximal eccentric actions (24ECC),
      on a second bout of 24ECC performed 2 weeks later. Male students (n = 34) were
      assigned to one of three groups, and with their non-dominant arm performed either
      2ECC (n = 12), 6ECC (n = 10), or 24ECC (n = 12) as a first bout of exercise. Two
      weeks later all groups performed 24ECC. Maximal isometric strength, range of
      motion, upper arm circumference, muscle soreness, plasma creatine kinase activity
      and myoglobin concentration were assessed before, immediately after, and for 4
      days after exercise. Changes in all variables were compared between the bouts and
      groups by a two-way repeated measures analysis of variance. All variables changed
      significantly (P< 0.05) after 2ECC, 6ECC, and 24ECC, but the amount of change
      after 2ECC and 6ECC was significantly smaller (P<0.05) than both 6ECC and 24ECC,
      and 24ECC, respectively. After the second bout, the 6ECC and 24ECC groups showed
      a profound repeated bout effect, and no significant differences were found
      between the groups. All variables except muscle soreness were significantly (P<
      0.05) larger after the second bout for the 2ECC group, however the changes
      observed after 24ECC were significantly smaller (P < 0.01) than those observed
      after the first 24ECC of the 24ECC group. These results suggest that it is not
      necessary to conduct a high number of eccentric actions in the first bout to
      elicit a repeated bout effect in a subsequent bout performed some time later.

PMID- 11513319
TI  - Cardio-respiratory adjustments and cost of locomotion in school children during
      backpack walking (the Italian Backpack Study).
AB  - The use of a school backpack is one of the possible causes of back pain in
      children. Oxygen consumption (VO2), pulmonary ventilation, and heart rate (fc)
      were measured in 35 pre-pubertal subjects [17 girls and 18 boys, mean (SD) age
      11.3 (0.6) years]. They took part in a four-step experiment: (1) standing for 5
      min, (2) walking at 3 km.h(-1) for 7 min, (3) walking at 3 km.h(-1) for 7 min
      carrying a school backpack weighing 8 kg, and (4) walking at 7 km.h(-1) for 5 min
      with no load. The occurrence of back pain in the last 2-3 years and during the
      last 15 days was assessed for the subjects by means of a questionnaire. Mean (SD)
      standing VO2, was 215 (45) ml.min(-1) during walking at 3 km.h(-1), 503 (101)
      ml.min(-1) during walking without a load, and increased to 541 (98) ml.min(-1)
      during walking with a load (P<0.01). Carrying a backpack increased fc only
      minimally. The energy cost of walking at 3 km.h(-1) without the backpack was 10.0
      (2.0) ml O2.m(-1), and with the backpack was 10.8 (1.9) ml O2.m(-1) (P< 0.01).
      The net energy cost of locomotion was 0.129 (0.032) ml.kg body mass(-1).m(-1) for
      the unloaded condition and slightly lower, at 0.123 (0.025) ml.kg body mass(
      1).m(-1) during loaded walking (P < 0.05). Ventilation did not change
      significantly between unloaded and loaded conditions. When the data were assessed
      according to the occurrence of back pain, the fc/VO2 slope was significantly
      lower in children without back pain, even though the net energy cost of
      locomotion was similar. Overall, these data suggest that the cardiovascular
      effortrequired for locomotion while carrying a backpack is minimal. However,
      fatigability and back pain are more likely to take place in less physical
      performing subjects. Thus, the occurrence of back pain in schoolchildren during
      locomotion while carrying a backpack may improve with an improvement in their
      level of fitness.

PMID- 11513320
TI  - Impaired pressor response after spaceflight and bed rest: evidence for
      cardiovascular dysfunction.
AB  - We hypothesized that impaired cardiovascular responses to isometric muscle action
      contribute to the cardiovascular deconditioning that occurs after space flight
      (SF) and head-down-tilt bed rest (HDT). Six subjects were studied before, during
      and after 120 days of -6 degrees HDT, and four subjects were studied before,
      during (two subjects) and after 179-389 days of SF. Subjects performed a
      sustained handgrip (SHG) at a force equivalent to 30% of maximum contraction
      force for 2 min, and heart-rate (HR) and pressor (mean arterial pressure,
      deltaMAP) responses were recorded. At the same relative force, both deltaHR and
      deltaMAP were significantly reduced during the first days after HDT (-54%, P<0.05
      and -43%, P<0.05). In two subjects studied within 24 h after their return from
      SF, deltaMAP was practically absent (-79%, P<0.05) whereas in four subjects
      studied 1-4 days after return from SF, deltaMAP was reduced by 35% (P<0.05).
      deltaHR was not significantly changed. Our finding of attenuated pressor
      responses to SHG after HDT and SF supports the notion of impairments at both the
      neurocirculatory control and effector organ levels.

PMID- 11513321
TI  - Effect of exercise intensity on the changes in alveolar slopes of carbon dioxide
      and oxygen expiratory profiles in humans.
AB  - The slope of the expired alveolar partial pressure of carbon dioxide profile
      increases during exercise. Its relationship to metabolic rate, however, remains
      to be determined at high exercise intensities. We therefore determined the slope
      of alveolar partial pressures of carbon dioxide and oxygen (PACO2, PAO2,
      respectively) during incremental cycle ergometer exercise (an increment of 40 W
      each minute) to exhaustion in 11 normal subjects. The PACO2 and PAO2 increased as
      linear functions of carbon dioxide production and oxygen uptake (VO2),
      respectively, up to the estimated lactate threshold (thetaLa-). At higher
      intensities PACO2 increased disproportionately but PAO2 continued to increase at
      the same rate in 7 subjects but increased more rapidly in the remainder. The rate
      of change in PACO2 per unit rate of change in VO2 averaged 3.15 (SD 1.05)
      (mmHg.s(-1)). (l.min(-1))-1 while the rate of change in PAO2 per unit rate of
      change in VO2 averaged -3.53 (SD 0.79) (mmHg.s(-1)) (l.min(-1))-1 over this
      range. The more rapid increase in PACO2 above thetaLa- was consistent with an
      accelerated CO2 exchange, whereas the more rapid rate of change in PAO2 in 3 of
      the subjects may have reflected the development of an increased distribution of
      the ventilation perfusion ratio in addition to the effects of hyperventilation.

PMID- 11513322
TI  - Heart rate profiles and energy cost of locomotion during cross-country skiing
      races.
AB  - The purpose of this study was to compare heart rate responses and speed in two
      cross-country skiing races, which were run by seven male and seven female
      subjects by using classic and free style. Heart rates and skiing velocities were
      analyzed over flat, uphill and downhill sections, which were run from one to
      three times. Heart rates were higher in uphill sections than in flat sections; a
      steady-state heart rate was never reached in the downhill section. When the same
      uphill section was repeated, the heart rate tended to increase but the speed to
      decrease. Oxygen uptake (VO2) was calculated from heart rate:VO2 ratio, measured
      during uphill walking with the aid of poles. The mean (SD) energy cost of
      locomotion (i.e., the ratio between net VO2 and speed) was 162.1 (9.4) ml.km(
      1).kg(-1) and 147.7 (7.1) ml.km(-1).kg(-1) when male subjects ran the flat
      section after first downhill by using classic and free style, respectively.
      Females had lower values for VO2 and speed, but similar energy costs. In general,
      the variability of the energy cost of locomotion in skiers of a similar
      competitive level is of the same order as that found in uphill walking on a
      treadmill.

PMID- 11513323
TI  - Substrate oxidation during acute exercise and with exercise training in lean and
      obese women.
AB  - The purpose of this study was to examine the rates of substrate oxidation in lean
      and obese women during short-duration, high-intensity exercise and to examine the
      effects of a 16-week exercise training program on substrate oxidation during 30
      min of exercise in lean and obese individuals. Fat and carbohydrate oxidation
      were measured in 8 non-obese (Non-Ob), 11 lower-body obese (LBO) and 12 upper
      body obese (UBO) women at rest and during 30 min of treadmill exercise at 70% of
      peak oxygen uptake. The obese women participated in 16 weeks of aerobic training
      (3 times per week at 70% of maximum oxygen uptake). Total fat and carbohydrate
      oxidation were measured using indirect calorimetry. The respiratory exchange
      ratio (R) was similar between groups at rest and was found to decrease throughout
      the exercise session (P< 0.01). Fat oxidation was greater at 15 min of exercise
      than at rest (P<0.01) but did not increase significantly more at 30 min of
      exercise. Obese women had significantly greater fat oxidation (both absolute
      concentrations and when expressed per kg of fat free mass, FFM) at 30 min of
      exercise than the Non-Ob women [Non-Ob 23.5 (3.7) micromol.kg FFM(-1).min(-1),
      LBO 35.2 (3.1) micromol.kg FFM(-1).min(-1), UBO 33.2 (2.6) micromol.kg FFM(
      1).min(-1); P<0.01]. Carbohydrate oxidation also increased (P < 0.01) in response
      to exercise, but no group differences were found. The pattern of fat distribution
      (LBO vs UBO) did not affect the resting or exercise fat oxidation (P=NS). Sixteen
      weeks of aerobic exercise did not result in significant changes in resting or
      exercise fat oxidation in the obese women (n = 10; P=NS), but did significantly
      increase carbohydrate oxidation [pretraining 8.6 (1.4) micromol.kg FFM(-1), post
      training 13.6 (2.1) micromol.kg FFM(-1).min(-1); P<0.01]. Unlike earlier studies,
      this shorter-duration, higher-intensity exercise resulted in a greater whole-body
      fat oxidation in the obese women than in the Non-Ob women, and exercise training
      did not result in any changes in fat oxidation, but did increase exercise
      carbohydrate oxidation.

PMID- 11513325
TI  - Cardiorespiratory responses to exercise in acute hypoxia, hyperoxia and normoxia.
AB  - There is a prevailing hypothesis that an acute change in the fraction of oxygen
      in inspired air (F(I)O2) has no effect on maximal cardiac output (Qcmax),
      although maximal oxygen uptake (VO2max) and exercise performance do vary along
      with F(I)O2. We tested this hypothesis in six endurance athletes during
      progressive cycle ergometer exercise in conditions of hypoxia (FI(O)2 = 0.150),
      normoxia (F(I)O2 = 0.209) and hyperoxia (F(I)O2=0.320). As expected, VO2max
      decreased in hypoxia [mean (SD) 3.58 (0.45)l.min(-1), P<0.05] and increased in
      hyperoxia [5.17 (0.34) l.min(-1), P<0.05] in comparison with normoxia [4.55
      (0.32)l.min(-1)]. Similarly, maximal power (Wmax) decreased in hypoxia [334 (41)
      W, P< 0.05] and tended to increase in hyperoxia [404 (58) W] in comparison with
      normoxia [383 (46) W]. Contrary to the hypothesis, Qcmax was 25.99 (3.37) l.min(
      1) in hypoxia (P<0.05 compared to normoxia and hyperoxia), 28.51 (2.36) l.min(-1)
      in normoxia and 30.13 (2.06)l.min(-1) in hyperoxia. Our results can be
      interpreted to indicate that (1) the reduction in VO2max in acute hypoxia is
      explained both by the narrowing of the arterio-venous oxygen difference and
      reduced Qcmax, (2) reduced Qcmax in acute hypoxia may be beneficial by preventing
      a further decrease in pulmonary and peripheral oxygen diffusion, and (3) reduced
      Qcmax and VO2max in acute hypoxia may be the result rather than the cause of the
      reduced Wmax and skeletal muscle recruitment, thus supporting the existence of a
      central governor.

PMID- 11513324
TI  - Influence of head-down bed rest on the circadian rhythms of hormones and
      electrolytes involved in hydroelectrolytic regulation.
AB  - We investigated in six men the impact of a 17-day head-down bed rest (HDBR) on
      the circadian rhythms of the hormones and electrolytes involved in
      hydroelectrolytic regulation. This HDBR study was designed to mimic an actual
      spaceflight. Urine samples were collected at each voiding before, during and
      after HDBR. Urinary excretion of aldosterone, arginine vasopressin (AVP), cyclic
      guanosine monophosphate (cGMP), cortisol, electrolytes (Na+ and K+) and
      creatinine were determined. HDBR resulted in a significant reduction of body mass
      (P < 0.01) and of caloric intake [mean (SEM) 2,778 (37) kcal.24 h(-1) to 2,450
      (36) kcal.24 h(-1), where 1 kcal.h(-1) = 1.163 J.s(-1); P< 0.01]. There was a
      significant increase in diastolic blood pressure [71.8 (0.7) mmHg vs 75.6 (0.91)
      mmHg], with no significant changes in either systolic blood pressure or heart
      rate. The nocturnal hormonal decrease of aldosterone was clearly evident only
      before and after HDBR, but the day/night difference did not appear during HDBR.
      The rhythm of K+ excretion was unchanged during HDBR, whereas for Na+ excretion,
      a large decrease was shown during the night as compared to the day. The circadian
      rhythm of cortisol persisted. These data suggest that exposure to a 17-day HDBR
      could induce an exaggeration of the amplitude of the Na+ rhythm and abolition of
      the aldosterone rhythm.

PMID- 11513326
TI  - Cardiovascular responses during arm exercise and orthostatic challenge in
      individuals with paraplegia.
AB  - In this study the cardiorespiratory responses during arm crank ergometry (ACE)
      performed at two submaximal intensities (30% and 50% of heart rate reserve) and
      moderate orthostatic challenge were investigated in individuals with paraplegia
      (PARA). The effect of concurrent electrical stimulation (ES)-induced leg muscle
      contractions on the responses to ACE during orthostatic challenge was also
      investigated. Eight PARA (T5-T12) and eight able-bodied (AB) individuals
      participated in this study, however only seven subjects from each group completed
      all tests and were used in subsequent data analyses. Oxygen uptake (VO2), heart
      rate (fc), stroke volume (SV) and cardiac output (Qc) were assessed during (1)
      ACE alone, (2) ACE and lower body negative pressure (ACE + LBNP), and, in PARA
      only, (3) ACE + LBNP with ES (ACE + LBNP+ ES). In both PARA and AB, ACE + LBNP
      decreased SV (by 13-18% and 20-23%, respectively) and increased fc (by 13-15% and
      16%, respectively) compared to ACE alone. The decrease in SV was greater in AB
      than in PARA (significant group x trial interaction; both ACE intensities
      pooled), but there was no difference in the magnitude of increase in fc between
      groups. ES-induced leg muscle contractions increased SV (up to 16%) but did not
      change VO2 or Qc. The smaller reduction in SV from ACE to ACE + LBNP in PARA may
      indicate a mechanism by which adequate central blood volume can be maintained in
      the face of orthostatic challenge, despite the absence of supraspinal control
      below the spinal cord lesion. With ES-induced leg muscle contractions, the
      decrease in SV, which occurred during ACE + LBNP, was reversed via reactivation
      of the lower limb muscle pump and augmented venous return.

PMID- 11513327
TI  - Hyperbaric O2 reduces intestinal ischemia-reperfusion-induced TNF-alpha
      production and lung neutrophil sequestration.
AB  - Treatment with hyperbaric O2 (HBO) ameliorates ischemia-reperfusion (I/R) injury.
      Since tumor necrosis factor-alpha (TNF-alpha) plays an important role in I/R
      injury, we hypothesized that the effect of HBO in I/R injury may be due to its
      ability to inhibit TNF-alpha production. In this study, one group of rats
      received HBO during 60 min of ischemia (HBO group, n = 9), while control rats
      endured the same procedure but did not receive HBO (non-HBO, n = 9). A group of
      sham-operated control rats (SHAM, n = 6) underwent laparotomy without occlusion
      of the artery and HBO treatment. Intestinal I/R led to an increase in serum TNF
      alpha concentration to [mean (SEM)] 165 (32) pg/ml (P < 0.01 vs SHAM rats). HBO
      attenuated this increase [34 (9) pg/ml; P<0.05 vs non-HBO group]. Intestinal I/R
      also resulted in a marked increase in lung myeloperoxidase content [0.62 (0.04)
      U/g vs 0.17 (0.02) U/g of SHAM rats, P<0.01]. HBO suppressed this increase [0.40
      (0.04) U/g, P<0.05 vs non-HBO rats]. HBO ameliorated the injury to the intestine
      and lung. The number of neutrophils sequestered in the lung was reduced in HBO
      rats compared to non-HBO rats [6.4 (0.9) neutrophils/per oil field and 10.9 (2)
      neutrophils/per oil field, respectively; P < 0.05]. These findings demonstrate
      that HBO inhibits TNF-alpha production during intestinal I/R, and this reduced
      TNF-alpha production may be attributed to the beneficial effects of HBO.

PMID- 11513328
TI  - Mechanism-based inactivators as probes of cytochrome P450 structure and function.
AB  - The cytochromes P450 superfamily of enzymes is a group of hemeproteins that
      catalyze the metabolism of an extensive series of compounds including drugs,
      chemical carcinogens, fatty acids, and steroids. They oxidize substrates ranging
      in size from ethylene to cyclosporin. Although significant efforts have been made
      to obtain structural information on the active sites of the microbial P450s,
      relatively little is currently known regarding the identities of the critical
      amino acid residues in the P450 active sites that are involved in substrate
      binding and catalysis. Since information on the crystal structures of the
      eukaryotic P450s has been relatively limited, investigators have used a variety
      of other techniques in attempts to elucide the structural features that play a
      role in the catalytic properties and substrate specificity at the enzyme active
      site. These include site-directed mutagenesis, natural mutations, homology
      modeling, mapping with aryl-iron complexes, affinity and photoaffinity labeling,
      and mechanism-based inactivators. A variety of different mechanism-based
      inactivators have proven to be useful in identifiying active site amino acid
      residues involved in substrate binding and catalysis. In this review we present a
      sampling of the types of studies that can be conducted using mechanism-based
      inactivators and highlight studies with several classes of compounds including
      acetylenes, isothiocyanates, xanthates, aminobenzotriazoles, phencyclidine, and
      furanocoumarins. Labeled peptides isolated from the inactivated proteins have
      been analyzed by N-terminal amino acid sequencing in conjunction with mass
      spectrometry to determine the sites of covalent modification. Mechanistic studies
      aimed at identifying the basis for the inactivation following adduct formation
      are also presented.

PMID- 11513329
TI  - Cytochrome P450 in the brain; a review.
AB  - After many frustrating decades of unsuccessful attempts to characterize the
      isoforms of P450 in the brain, several scientific breakthroughs in the 80s and
      90s have resulted in major advances in our understanding of cytochromes P450
      (CYP) in brain. We now know that classical CYP inducers, e.g. phenobarbital and
      pregnenolone 16alpha-carbonitrile, which regulate drug-metabolizing enzymes in
      the liver, are specific ligands for ligand-activated transcription factors, and
      that the brain content of many of these transcription factors is low. This
      explains why these inducers have little effect on brain CYP content. The most
      effective inducers of brain P450 are some of the CNS active drugs and solvents.
      The level of CYPs in brain, approximately 0.5-2% of that in liver, is too low to
      significantly influence the overall pharmacokinetics of drugs and hormones in the
      body. Instead CYPs appear to have specific functions in brain, e.g. regulation of
      the levels of endogenous GABAA receptor agonists maintenance of brain cholesterol
      homeostasis and elimination of retinoids The novel CYPs which catalyse these
      reactions have recently been characterized. They are abundantly expressed in the
      brain confirming what has been previously found, i.e. that the major hepatic,
      adrenal and gonadal CYP isozymes contribute very little to the overall content of
      CYP in brain. It is not clear what fraction of brain CYP has been characterized,
      although a complete characterization of constitutive and induced CYPs in brain is
      essential for understanding the role of these enzymes in brain physiology as well
      as in age-related and xenobiotic-induced neurotoxicity.

PMID- 11513331
TI  - Human UDP-glucuronosyltransferase 2B7.
AB  - UDP-Glucuronosyltransferases (UGTs) are glycoproteins, localized in endoplasmic
      reticulum (ER) and nuclear membranes, which catalyze the confugation of a broad
      variety of lipophilic aglycon substrates with glucuronic acid using UDP
      glucuronic acid (UDP-GlcUA) as the sugar donor. The major function of
      glucuronidation is to change hydrophobic compounds into hydrophilic derivatives,
      a process which facilitates their detoxification and excretion. However, it is
      also widely recognized that glucuronidation can result in compounds which are
      biologically active or demonstrate increased toxicity. UGTs, like other drug
      metabolizing enzymes, have been postulated to be involved in controlling the
      steady state concentrations of nuclear receptor ligands for interactions with
      nuclear receptors [1,2]. One of the isoforms from the UGT2B subfamily, UGT2B7,
      has been found to be a major human UGT2B isoform, involved in the glucuronidation
      of a variety of endogenous compounds and xenobiotics. In this review, we included
      all available information from our studies and those of other investigators on a)
      the history of the identification and expression of UGT2B7 in human tissues, b)
      the substrate specificity of UGT2B7, c) the extrahepatic localization of UGT2B7
      d) the nuclear localization of UGT2B7 and e) characterization of the UGT2B7 gene
      and promoter.

PMID- 11513330
TI  - Cytochrome P450 4A fatty acid omega hydroxylases.
AB  - The Cytochrome P450 4A subfamily is one of eighteen subfamilies in the CYP4
      family and presently consists of twenty individual forms in nine different
      mammalian species. The major substrates for CYP4A forms are fatty acids, but
      recent studies have shown other non-fatty acid substrates may be metabolized by
      specific CYP4A forms. The physiological and metabolic functions of the CYP4A
      subfamily have not been elucidated, but the ability of CYP4A forms to metabolize
      medium and long chain length fatty acids at their omega (omega)-carbon atom has
      generated significant interest because of the possible role that omega
      hydroxylated fatty acids may have in cell signalling processes and as an
      alternative pathway for fatty acid metabolism. A number of different compounds or
      physiological conditions have been shown to regulate the expression of CYP4A
      forms in liver and/or kidney. Several CYP4A forms may serve as a marker for the
      exposure to compounds that are classified as peroxisome proliferators. There is
      also considerable interest why multiple CYP4A forms exist in different tissues.
      Recent studies in the rat and human indicate that other CYP4 forms besides CYP4A
      forms may be responsible for the metabolism of arachidonic acid to its omega
      hydroxy product. The focus of this review will be to summarize recent studies
      that have characterized the substrate specificity of rat, rabbit and human CYP4A
      forms and discuss the significance of CYP4A-mediated hydroxylation of fatty
      acids. In addition, dietary effects or novel compounds that have been reported to
      regulate CYP4A expression in the rat and mouse will be discussed.

PMID- 11513332
TI  - The use of in vitro methods to predict in vivo pharmacokinetics and drug
      interactions.
AB  - With the dramatic change underway in the process of drug discovery and
      development it has become increasingly important to define, both qualitatively
      and quantitatively, the dispositional features of new chemical entities (NCEs) as
      early in the process as possible. To that end strategies have emerged that are
      designed to enable reasonable predictions about a NCE's absorption from the
      gastrointestinal tract, systemic bioavailability and likelihood for significant
      pre-systemic clearance, character of metabolic processing both within the
      gastrointestinal tract and the liver, in vivo pharmacokinetics (PK), and
      likelihood for clinically significant interactions with other drugs. To some
      extent these strategies have embraced interspecies allometric scaling in which
      findings in animals are extrapolated to predict outcomes in humans. However, a
      greater emphasis in recent years has been placed on predicting human PK and the
      likelihood of clinically significant drug-drug interactions for NCEs solely from
      in vitro experiments. These general strategies have been methodologically
      streamlined so that hundreds or even thousands of experiments on a given NCE can
      be conducted within several days. Dispositional data from these pre-clinical
      experiments is useful for rapidly identifying potential marketing advantages for
      NCEs, and for screening out those substances that should not be placed into more
      expensive and labor-intensive animal experiments or brought to clinical trial.
      The key issue in these strategies is the accuracy with which pre-clinical
      findings predict clinical outcomes. Based largely on retrospective analyses the
      current state of the art exhibits a high percentage of useful predictions.
      However, there are many examples in which the prediction of either human PK or
      clinical drug-drug interactions from pre-clinical data has failed. The reasons
      for inaccurate predictions are manifold, and may include the actual in vitro
      methodology used, inappropriate model selection, and errant scale-up factors.
      Additionally, in vitro methods may fail to account for complex hepatobiliary
      processing including transport phenomena and Phase II metabolism. Progress has
      been made in establishing humanized methodologies that accurately describe these
      processes, with a view toward reconstituting the contributions of each into a
      more complex and accurate depiction and prediction of in vivo PK and drug
      interaction potential.

PMID- 11513333
TI  - Modulation of inducible nitric oxide synthase activation by immunosuppressive
      drugs.
AB  - The activation of inducible form of nitric oxide (NO) synthase (iNOS, type II, or
      macrophage NOS) and subsequent production of free radical gas NO is an important
      anti-infectious and anti-tumor mechanism of innate immunity. On the other hand,
      high amounts of iNOS-derived NO have been implicated in self-tissue destruction
      during autoimmune diseases, allograft rejection, sepsis, and other disorders
      accompanied by excessive activation of the immune system. It is generally
      accepted that beneficial effects of some recently designed immunosuppressive
      agents primarily stem froin their ability to interfere with the function of T
      and/or B cells, thus preventing deleterious consequences of specific immunity
      innate immunity positive feedback, with high NO production being one of them.
      However, it has been recently observed that drugs like cyclosporin A, FK506,
      leflunomide, mycophenolate mofetil, pentoxifylline, and linomide can directly
      modulate cytokine and/or LPS-induced NO production in various cell types in
      vitro, probably by interfering with iNOS gene transcription or catalytic activity
      of iNOS enzyme. Interestingly, some of these drugs exhibited cell-specific
      pattern of iNOS modulation, thus indirectly revealing distinct requirements for
      iNOS induction in different cell types. Possible impact of this direct and cell
      selective interference with iNOS activation on the therapeutic effectiveness of
      immunosuppressive drugs is discussed.

PMID- 11513334
TI  - Agents for the treatment of glycosphingolipid storage disorders.
AB  - We have developed a series of inhibitors of glucosylceramide synthase that are
      structurally based on the parent compound D-threo-1-phenyl-2-decanoylamino-3
      morpholino-1-propanol (PDMP). These inhibitors provide useful tools for
      manipulating glycosphingolipid levels in cells and for elucidating questions
      associated with sphingolipid signaling. Recently, two highly active
      glucosylceramide synthase inhibitors, D-threo-3', 4'-ethylenedioxy-1-phenyl-2
      palmitoylamino-3- pyrrolidino-1-propanol and D-threo-4'-hydroxy-1-phenyl-2
      palmitoylamino-3- pyrrolidino-1-propanol, were designed, synthesized, and
      studied. These inhibitors markedly reduced glycosphingolipid levels in MDCK cells
      without any accumulation of intracellular ceramide and associated growth
      inhibition. Subsequently, each inhibitor was evaluated for its ability to lower
      glycolipid levels in virally transformed lymphoblasts from a patient with alpha
      galactosidase A deficiency. Both compounds significantly reduced neutral
      glycosphingolipid levels in the lymphoblasts without any morphological changes
      and growth inhibition. Furthermore, the inhibitors were applied to a mouse
      knockout model of Fabry disease. Inhibitor treatment blocked accumulation of
      globotriaosylceramide (Gb3) in the kidney, liver and heart of mice. In contrast
      to another glucosylceramide synthase inhibitor, N-butyldeoxynojirimycin, this
      treatment was not associated with any significant change in body weight or organ
      weight and without immunodepletion. These results suggest that these newest PDMP
      homologues are promising as therapeutic agents for the treatment of
      glycosphingolipid storage disorders.

PMID- 11513335
TI  - Oligodendrogliomas: the Achilles' heel of malignant gliomas.

PMID- 11513336
TI  - Do case series have a role in an evidence-based medical culture?

PMID- 11513337
TI  - Status of current clinical trials in diabetic polyneuropathy.
AB  - Peripheral polyneuropathy is the most frequent complication of diabetic mellitus.
      In spite of many clinical trials of different specific interventions for diabetic
      polyneuropathy, intensive glycemic control remains the only effective specific
      therapy currently available for this troublesome complication. This systematic
      overview reports the status of current clinical trials in diabetic polyneuropathy
      with an emphasis on those interventions directed towards specific
      pathophysiological derangements. A discussion of clinical trials of agents
      directed towards relieving painful symptoms of diabetic polyneuropathy concludes
      this overview.

PMID- 11513338
TI  - Progress in clinical neurosciences: Charcot-Marie-Tooth disease and related
      inherited peripheral neuropathies.
AB  - The classification of Charcot-Marie-Tooth disease and related hereditary motor
      and sensory neuropathies has evolved to incorporate clinical,
      electrophysiological and burgeoning molecular genetic information that
      characterize the many disorders. For several inherited neuropathies, the gene
      product abnormality is known and for others, candidate genes have been
      identified. Genetic testing can pinpoint a specific inherited neuropathy for many
      patients. However, clinical and electrophysiological assessments continue to be
      essential tools for diagnosis and management of this disease group. This article
      reviews clinical, electrophysiological, pathological and molecular aspects of
      hereditary motor and sensory neuropathies.

PMID- 11513339
TI  - PCV for oligodendroglial tumors: in search of prognostic factors for response and
      survival.
AB  - BACKGROUND: We report survival and pretreatment prognostic factors for survival
      and chemosensitivity in 53 oligodendrogliomas treated with PCV (procarbazine,
      lomustine and vincristine) chemotherapy. METHODS: A total of 53 patients with
      histologically proven oligodendroglioma, anaplastic oligodendroglioma or oligo
      astrocytoma and treated with PCV were extracted from the London Regional Cancer
      Center database. A retrospective review was conducted to evaluate overall
      survival and pretreatment prognostic factors for survival and chemosensitivity.
      RESULTS: The median survival time from diagnosis was 123.6 months. The overall
      five- and ten-year survival rates were 72.7% and 52.7% respectively. Age <40,
      seizure as an initial symptom, absence of cognitive deficit and presence of a
      homogeneous hypodense lesion without contrast enhancement on the initial
      pretreatment CT scan were all factors independently associated with favorable
      outcome. The presence of increased cellularity, pleomorphism, mitosis, vascular
      proliferation and grading as an anaplastic lesion using these surrogates on
      pathological assessment, were all associated with an unfavorable outcome in
      univariable analysis. In multivariable analysis, only the anaplastic grading and
      presence of increased cellularity were significant determinants of unfavorable
      survival. The only factor adversely associated with chemosensitivity was the
      presence of a focal symptom at presentation. CONCLUSION: Overall survival is
      significantly longer in oligodendroglial lesions than in fibrillary astrocytic
      tumors. A two tier grading system using standard morphological features seems
      accurate in predicting outcome in these patients. The presence of a neoplastic
      astrocytic component does not seem to impact the outcome. No clinical,
      radiological or pathological factor could be identified to reliably predict
      chemotherapy response.

PMID- 11513340
TI  - Methylprednisolone may improve lumbosacral radiculoplexus neuropathy.
AB  - OBJECTIVE: To report on an open trial of intravenous methylprednisolone (IV MP)
      in nondiabetic lumbosacral radiculoplexus neuropathy (LSRPN). BACKGROUND:
      Lumbosacral radiculoplexus neuropathy is a subacute, unilateral or asymmetric
      syndrome of pain, weakness, and paresthesia of the lower extremity, which is
      attributed to ischemic injury from microvasculitis in lumbosacral roots, plexus,
      and nerves. METHODS: Eleven nondiabetic patients with worsening LSRPN were
      treated - ten with infusions of IV MP (1 gm/wk) for 8 to 16 weeks and one with an
      equivalent dosage of oral prednisone. The main endpoints evaluated were: 1) the
      Neuropathy Impairment Score (NIS), and 2) the Neuropathy Symptoms and Change
      (NSC) scores. RESULTS: The median age of our patients was 67 years, range 49 to
      86 years. Seven patients were women. All 11 patients reported improvement during
      treatment--nine reported marked improvement. The median NIS improved from 42
      points (range 9 to 106 points) before treatment, to 20 points (range 5 to 57
      points) (p = 0.005) after treatment. Pain was completely resolved in four
      patients and much improved in seven. The change subscore and the severity
      subscore of the NSC were statistically significantly improved after treatment.
      Prior to treatment, all patients had significant weakness with six confined to
      wheelchairs and four using mechanical devices to aid in ambulation. After
      treatment, the weakness was markedly improved in nine patients; only one still
      required a wheelchair and six walked independently (p = 0.03). CONCLUSIONS: 1) In
      LSRPN, pain and neurological deficits improved (often dramatically) with IV MP
      treatment. 2) Although our results should be interpreted with caution since this
      trial is uncontrolled, IV MP may favorably affect the natural history of LSRPN.
      3) The results are sufficiently promising to provide a rationale for prospective,
      sham controlled, double blind trials.

PMID- 11513341
TI  - Neurocognitive symptoms and impairment in an HIV community clinic.
AB  - BACKGROUND: Neurocognitive impairment is a frequent complication of HIV infection
      and heralds a poor survival prognosis. With the availability of highly active
      antiretroviral therapy (HAART), survival times for HIV-infected patients have
      markedly increased although the effects of HAART on the prevalence of
      neurocognitive impairment remain uncertain. OBJECTIVE: To determine the
      relationship between self-reported neurocognitive symptoms and neuropsychological
      (NP) performance together with the impact of HAART among HIV-infected patients.
      METHODS: A cross-sectional study was performed in which patients without
      previously documented neurocognitive impairment attending an HIV community clinic
      were questioned about neurocognitive symptoms and a NP test battery was
      administered. RESULTS: Of the eighty-three patients examined, neurocognitive
      symptoms were reported by 34% of patients and were associated with a shorter
      duration of HAART and higher viral loads. Patients reporting neurocognitive
      symptoms were also more likely to exhibit impaired NP performance (p<0.005) with
      NP impairment being detected in 46% of all patients examined (12% with HIV
      associated dementia). Neuropsychological impairment was directly correlated with
      age (p<0.001), plasma viral load (p<0.005) and inversely correlated with the
      number of prescribed antiretroviral drugs (p<0.01). CONCLUSIONS: These results
      suggest that neurocognitive symptoms are predictive of impaired NP performance
      and that NP impairment remains a frequent finding among older patients with
      higher viral loads. An increased number of antiretroviral drugs may be
      neuroprotective.

PMID- 11513343
TI  - Prospective analysis of relationships of outcome measures for ulnar neuropathy at
      the elbow.
AB  - BACKGROUND: We undertook a prospective study to investigate relationships between
      outcome measures of ulnar neuropathy at the elbow. METHODS: Thirty-one patients
      (mean age 52.6, range 20-80), with clinically and electrically verified ulnar
      neuropathy at the elbow, were seen independently by a neurosurgeon and a
      physiotherapist. All tests were administered to all patients on each visit. Data
      collected included measures of sensory (monofilament, two-point discrimination,
      vibration) and motor function (grip, key-pinch, muscle atrophy), pain (visual
      analogue scale (VAS)) and impact on lifestyle (Levine's questionnaires (function
      status score--FSS, symptom severity score--SSS)), disability of the arm, shoulder
      and hand module (DASH) and patient-specific measures (PSM). Parametric and non
      parametric correlation and factor analysis were done. RESULTS: Outcome analysis
      was available for 63 patient visits, with follow-up obtained for 20 patients
      (mean 8.5 months). Lifestyle and pain instruments (FSS, SSS, DASH, PSM and VAS)
      all correlated well with each other (r > 0.6, p < .01). DASH was moderately to
      highly correlated to nine of the 11 measures. Some tests correlated poorly, for
      example, Semmes-Weinstein monofilament with other sensory measures and muscle
      atrophy with almost all measures. Factor analysis revealed that there are two
      principal factors, accounting for 77% of the variance. Factor 1 relates to impact
      on lifestyle and pain while Factor 2 relates to strength and function.
      DISCUSSION/CONCLUSIONS: Intraclass measures, particularly ones assessing
      lifestyle and pain instruments are strongly correlated. Factor analysis revealed
      two principal factors that account for the majority of the variance; future
      studies with a larger sample size are needed to validate this analysis.

PMID- 11513342
TI  - Methodology for the Canadian Activase for Stroke Effectiveness Study (CASES). 
      CASES Investigators.
AB  - BACKGROUND: Intravenous recombinant tissue plasminogen activator (tPA, alteplase)
      was conditionally licensed for the treatment of acute ischemic stroke (AIS) in
      Canada on February 17, 1999. As a condition of licensure, the Canadian Activase
      for Stroke Effectiveness Study (CASES) was established to monitor the use of
      alteplase for AIS in Canada. The study involves multiple stakeholders. METHODS:
      CASES is a prospective registry of patients treated with alteplase for AIS. The
      purposes of this registry are to ensure the safety of the drug in the Canadian
      context, to assess effectiveness of alteplase for AIS and to gather further
      information to try to establish which patients are most likely to benefit from
      treatment. RESULTS: Both community (n=25) and tertiary centres (n=35) have
      enrolled a total of 944 patients to date. Early results suggest that thrombolytic
      stroke treatment is both safe and effective among these centres. CONCLUSIONS:
      This paper outlines the development of and methods for the CASES study. The study
      is an example of a multi-stakeholder collaboration to advance the care of
      patients with acute stroke.

PMID- 11513344
TI  - Identification of the temporal components of seizure onset in the scalp EEG.
AB  - BACKGROUND: The identification of the earliest indication of rhythmical
      oscillations and paroxysmal events associated with an epileptic seizure is
      paramount in identifying the location of the seizure onset in the scalp EEG. In
      this work, data-dependent filters are designed that can help reveal obscure
      activity at the onset of seizures in problematic EEGs. METHODS: Data-dependent
      filters were designed using temporal patterns common to selected segments from
      pre-ictal and ictal portions of the scalp EEG. Temporal patterns that accounted
      for more variance in the ictal segment than in the pre-ictal segment of the scalp
      EEG were used to form the filters. RESULTS: Application of the filters to the
      scalp EEG revealed temporal components in the seizure onset in the scalp
      recording that were not obvious in the unfiltered EEG. Examination of the
      filtered EEG enabled the onset of the seizure to be recognized earlier in the
      recording. The utility of the filters was confirmed qualitatively by comparing
      the scalp recording to the intracranial recording and quantitatively by
      calculating correlation coefficients between the scalp and intracranial
      recordings before and after filtering. CONCLUSION: The data-dependent approach to
      EEG filter design allows automatic detection of the basic frequencies present in
      the seizure onset. This approach is more effective than narrow band-pass
      filtering for eliminating artifactual and other interference that can obscure the
      onset of a seizure. Therefore, temporal-pattern filtering facilitates the
      identification of seizure onsets in challenging scalp EEGs.

PMID- 11513345
TI  - Spinal epidural abscess.

PMID- 11513346
TI  - Endovascular treatment of a lenticulostriate artery aneurysm with N-butyl
      cyanoacrylate.
AB  - BACKGROUND: Aneurysms arising from lenticulostriate artery branches in moyamoya
      type disease are challenging lesions to treat, due to their fragility and deep
      location. Surgery is difficult and endovascular options may be limited. METHODS:
      A 57-year-old woman presented with a right ganglionic parenchymal hemorrhage due
      to a ruptured lenticulostriate artery aneurysm associated with ipsilateral middle
      cerebral artery occlusion. The aneurysm and parent feeding artery were occluded
      using endovascular injection of N-butyl cyanoacrylate. RESULTS: The aneurysm was
      successfully obliterated and although some glue did enter the more distal middle
      cerebral artery, there was no change in the patient's neurologic status.
      CONCLUSIONS: In highly selected cases where lenticulostriate aneurysms cannot be
      directly accessed for surgery or endovascular coiling, obliteration with liquid
      acrylic glue may be considered as a therapeutic option.

PMID- 11513347
TI  - Encephalopathy with staphylococcal endocarditis: multiple neuropathological
      findings.
AB  - BACKGROUND: Infective endocarditis is associated with serious neurological
      sequelae. OBJECTIVE: Here, we report a patient with Staphylococcus aureus
      endocarditis, secondary to congenital heart disease, with subacute onset of
      multiple neurological complications. RESULTS: Despite prompt antibiotic treatment
      with rapid sterilization of blood cultures, the patient died with brain
      herniation within 96 hours of admission. Neuropathological examination showed
      intraparenchymal hemorrhages, mycotic aneurysms, micro-abscesses and septic
      arteritis with accompanying infarction. Immunocytochemical studies revealed
      enhanced CD45 and GFAP immunoreactivity, together with adenosine A1 receptor
      detection on macrophages and microglia. CONCLUSIONS: Infective endocarditis is
      associated with multiple neuropathological lesions, which may contribute to its
      poor clinical outcome and activation of cells of monocyte-microglial lineage
      throughout the brain.

PMID- 11513348
TI  - Spontaneous internal carotid artery dissection with lower cranial nerve palsy.
AB  - BACKGROUND: Typical presentation of spontaneous internal carotid artery (ICA)
      dissection is an ipsilateral pain in neck and face with Horner's syndrome and
      contralateral deficits. Although rare, lower cranial nerve palsy have been
      reported in association with an ipsilateral spontaneous ICA dissection. CASE
      STUDIES: We report three new cases of ICA dissection with lower cranial nerve
      palsies. RESULTS: The first symtom to appear was headache in all three patients.
      Examination disclosed a Horner's syndrome in two cases (1 and 2), an isolated
      XIIth nerve palsy in two patients (case 1 and 3) and IX, X, and XIIth nerve
      palsies (case 2) revealing an ipsilateral carotid dissection, confirmed by MRI
      and angiography. In all cases, prognosis was good after a few weeks. CONCLUSIONS:
      These cases, analysed with those in the literature, led us to discuss two
      possible mechanisms: direct compression of cranial nerves by a subadventitial
      haematoma in the parapharyngeal space or ischemic palsy by compression of the
      ascending pharyngeal artery.

PMID- 11513349
TI  - A systematic review of the use of triptans in acute migraine.

PMID- 11513350
TI  - Celastrol, a potent antioxidant and anti-inflammatory drug, as a possible
      treatment for Alzheimer's disease.
AB  - In the brains of patients with Alzheimer's disease (AD) signs of neuronal
      degeneration are accompanied by markers of microglial activation, inflammation,
      and oxidant damage. The presence of nitrotyrosine in the cell bodies of neurons
      in AD suggests that peroxynitrite contributes to the pathogenesis of the disease.
      A drug with antioxidant and anti-inflammatory activity may prevent neuronal
      degeneration in AD. Celastrol, a plant-derived triterpene, has these effects. In
      low nanomolar concentrations celastrol was found to suppress the production by
      human monocytes and macrophages of the pro-inflammatory cytokines TNF-alpha and
      IL-1beta. Celastrol also decreased the induced expression of class II MHC
      molecules by microglia. In macrophage lineage cells and endothelial cells
      celastrol decreased induced but not constitutive NO production. Celastrol
      suppressed adjuvant arthritis in the rat, demonstrating in vivo anti-inflammatory
      activity. Low doses of celastrol administered to rats significantly improved
      their performance in memory, learning and psychomotor activity tests. The potent
      antioxidant and anti-inflammatory activities of celastrol, and its effects on
      cognitive functions, suggest that the drug may be useful to treat
      neurodegenerative diseases accompanied by inflammation, such as AD.

PMID- 11513351
TI  - Cognitive decline in schizophrenics with Alzheimer's disease: a mini-review of
      neuropsychological and neuropathological studies.
AB  - Cognitive decline in elderly schizophrenic patients is an important clinical
      symptom, but it is often difficult to analyze in detail due to the patient's
      original residual psychotic symptoms. In this article, the authors provide
      neuropsychological and neuropathological research information about cognitive
      decline in elderly schizophrenic patients, especially with reference to
      Alzheimer's disease (AD). Neuropsychological and neuropathological reports about
      cognitive impairments are reviewed. The effect of long-term antipsychotic
      medication upon cognitive function is also discussed. As a result, it is apparent
      that elderly schizophrenic patients often show cognitive impairments, however,
      such impairments do not have the characteristics of progressive degenerative
      illnesses such as AD, and the speed of their progress is very slow.
      Neuropathological studies have shown that AD brain pathology appears no more
      frequently among schizophrenic patients than in the normal population. Since
      making a diagnosis of AD means that the progressive deterioration not only of
      cognitive function, but also of physical ability, paralleling the degeneration of
      the central nervous system, can be expected within a few years and appropriate
      care will be required. One should be very cautious in adding a diagnosis of AD to
      elderly schizophrenic patients with cognitive impairments.

PMID- 11513352
TI  - Factor analysis of the Montgomery Asberg Depression Rating Scale in 251 bipolar
      II and 306 unipolar depressed outpatients.
AB  - Symptomatological differences between bipolar II (n = 251) and unipolar (n = 306)
      depressed outpatients, interviewed with the Structured Clinical Interview for DSM
      IV, were studied by Montgomery Asberg Depression Rating Scale factor analysis.
      Different factors were found in bipolar II [factor 1 (apparent sadness, reported
      sadness), factor 2 (reduced sleep, reduced appetite), factor 3 (concentration
      difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal
      thoughts)], and in unipolar [factor 1 (apparent sadness, reported sadness,
      inability to feel, suicidal thoughts), factor 2 (concentration difficulties,
      lassitude, inability to feel, pessimistic thoughts), factor 3 (inner tension,
      reduced sleep)]. Different factor structure (between bipolar II and unipolar
      depression) supports previous findings that response to antidepressants and
      biology may be different in bipolar II and unipolar depression.

PMID- 11513353
TI  - Clinical features and alterations in the inferior horn sizes in lateral ventricle
      in Alzheimer's patients with different ApoE genotype in Japanese population.
AB  - E4 allele of Apolipoprotein E (ApoE) is considered to be not only a risk factor
      for Alzheimer's disease (AD) but also a determinant of clinical features in AD.
      However, it is still controversial whether ApoE e4 allele is related to age at
      onset, severity of memory impairment or brain morphological changes in AD
      patients. The present study examined the issue in Japanese population: 1) ApoE
      genotype on in 38 normal controls and 32 AD patients; 2) association between e4
      allele of ApoE and clinical features including Wechsler Memory Scale-Revised in
      32 AD patients; and 3) association between e4 allele of ApoE and change in size
      of inferior horn in lateral ventricle (LV) in 13 out of 32 AD patients. The e4
      allele of ApoE frequency was higher in AD patients than in normal controls. There
      was no significant difference in age at onset or neuropsychological results
      between AD with and without e4 allele of ApoE. Alteration per month of the
      inferior horn sizes in LV measured by MRI was similar in the AD patients with and
      without e4 allele of ApoE. These results suggest that e4 allele of ApoE is a risk
      factor but not a determinant of clinical features for AD in Japanese population.

PMID- 11513354
TI  - Sensitization of adenylate cyclase induced by a dopamine D2 receptor mutant:
      inverse agonism by D2 receptor antagonists.
AB  - Mutations of residues in the third intracellular loops of several G-protein
      coupled receptors have been shown to confer constitutive activation. The authors
      investigated the effects of one such mutation in the dopamine D2 receptor.
      Compared to the wild type D2, the mutant D2 receptor (D2T344K) showed a
      substantial increase in agonist affinity with affinity for antagonists unchanged.
      The increased agonist affinity was unaffected by pertussis toxin treatment,
      indicating it is an intrinsic property of the mutant receptor. The potency of
      dopamine for acute inhibition of forskolin-stimulated cAMP production in stably
      expressing Chinese Hamster Ovary (CHO) cells was higher for the mutant than the
      wild type receptor. CHO cells stably expressing D2T344K displayed enhanced
      responses to forskolin-stimulated adenylate cyclase activity compared with cells
      stably expressing the wild type D2 receptor. The increased forskolin
      responsiveness of adenylate cyclase is similar to the sensitization previously
      observed with wild type D2 receptor after agonist treatment. Adenylate cyclase
      responsiveness of CHO cells stably expressing D2T344K receptor was not further
      increased by agonist treatment. Sensitization was blocked by pertussis toxin and
      D2 receptor antagonists haloperidol, butaclamol, and clozapine, indicating
      inverse agonist activity of these compounds at D2T344K. Inverse agonist activity
      was further demonstrated by the finding that overnight treatment with these
      compounds drastically increased the density of the mutant receptor but had
      minimal effect on the density of the wild type receptor. Taken together, these
      results suggest the authors have generated a constitutively active dopamine D2
      receptor capable of sensitizing adenylate cyclase in the absence of agonist
      activation.

PMID- 11513355
TI  - Dose-related effects of chronic gestational cocaine treatment on maternal
      aggression in rats on postpartum days 2, 3, and 5.
AB  - Gravid Sprague-Dawley rats received subcutaneous injections of saline, 3.5, 7.5
      or 15 mg/kg of cocaine, twice daily, throughout gestation. On postpartum days 2,
      3, and 5, dams and their litters (surrogate or natural) were videotaped for 10
      minutes in the presence of a male rat for assessment of aggression towards the
      intruder. Oxytocin levels in discrete brain areas were assayed on postpartum day
      5. The 30 mg/kg dose group had a significantly greater increase in the frequency
      of threats from postpartum day2 through postpartum day 5 than the 7.5 mg/kg
      cocaine and the non-yoke-fed saline control groups. Dams with natural litters
      exhibited a significantly greater frequency of receptive behavior compared to
      dams with surrogate litters. There were no significant differences in oxytocin
      levels between the 30 mg/kg cocaine-treated group and the other treatment or
      control groups on postpartum day 5. There are very few statistically significant
      cocaine-induced increases in maternal aggressive behavior and no dose-dependent
      decreases in amygdaloid OT levels in the early postpartum period.

PMID- 11513356
TI  - Effects of chronic cocaine administration on aggressive behavior in virgin rats.
AB  - Virgin Sprague-Dawley rats received subcutaneous injections of saline, 3.5, 7.5
      or 15 mg/kg of cocaine, twice daily, for 20 consecutive days. Females were
      videotaped for 10 minutes in the presence of a male rat for assessment of
      aggression towards the intruder 2, 3, and 5 days following cessation of cocaine
      or saline administration. Oxytocin levels in discrete brain areas were assayed
      following behavioral testing, 5 days following cessation of cocaine or saline
      administration. The 30 mg/kg-dose group tended to have a lower frequency of fight
      attacks and aggressive postures compared to saline-treated controls across
      sessions. The frequency of most of the behaviors analyzed were represented by
      quadratic functions across time, such that the highest frequency of behavior
      occurred 2 days following the final injection with relatively less activity 3 and
      5 days following cessation of saline or cocaine administration. The 30 mg/kg
      cocaine-treated group had significantly lower hippocampal OT levels than the 15
      mg/kg group 5 days following cessation of cocaine or saline administration.

PMID- 11513357
TI  - Small platform stress increases exploratory activity of mice in staircase test.
AB  - Small platform (SP) stress was induced by placing mice on small platforms (3.5 cm
      diameter) surrounded by water for 24 h. This model contains several factors of
      stress like rapid eye movement (REM) sleep deprivation, isolation, immobilization
      and falling into the water. The staircase test consisted of placing a mouse in an
      enclosed staircase with 5 steps and recording (1) the number of steps and (2)
      rearings made during 3 min. SP stress increased the exploratory activity of mice
      in the staircase test as evidenced by an increase in the number of steps and
      rearings made In control mice diazepam (0.25 and 0.5 mg/kg) induced an anxiolytic
      effect in the staircase test as evidenced by a decrease in the number of rearings
      without changes in the number of steps. In SP stressed mice the anxiolytic effect
      of diazepam was not seen and the sedative effect as evidenced by a decrease in
      the number of steps was more pronounced. Buspirone at a dose of 1.0 mg/kg did not
      have effect on the behaviour of control or SP stressed mice in the staircase
      test. To study possible diurnal variations the staircase test was carried out at
      3 different times of a day (08:00, 14:00, 20:00) with control and SP stressed
      mice. The exploratory activity of control mice in the staircase test gradually
      increased from 08:00 to 20:00 as evidenced by an increased number of steps and
      rearings made. SP stress increased the exploratory activity of mice irrespective
      of the time of testing. In conclusion, on the basis of these data the authors can
      propose that SP stress increases the exploratory activity of mice in the
      staircase test and induces a hyposensitivity of mice to the anxiolytic effect of
      diazepam. The effect of SP stress on the behaviour of mice in the staircase test
      is not caused by the disruptance of diurnal rhythms.

PMID- 11513358
TI  - Nicotine attenuates DOI-induced head-twitch response in mice: implications for
      Tourette syndrome.
AB  - Tourette syndrome (TS), a chronic neuropsychiatric disorder, is characterized by
      motor and vocal tics. Preliminary clinical studies indicate possible therapeutic
      benefits of nicotine in the treatment of Tourette's syndrome (TS). It has been
      proposed that twitches of the head in mice or twitches of head and shoulders in
      rats following administration of the selective 5HT(2A/C) agonist DOI (1-)2,5
      dimethoxy-4-iodophenyl-2-aminopropane, can serve as an animal model of tics in
      TS. In this study, the effects of acute and chronic administration of nicotine on
      DOI-induced head twitch response (HTR) in male albino ICR mice were evaluated.
      Both acute and chronic nicotine (daily injections for 10 days) reduced the DOI
      induced HTR. Moreover, chronic administration of DOI (1 mg/kg/day for 10 days)
      resulted in 65% increase in [125I]alpha-bungarotoxin binding in cerebellum and
      41% increase in striatal [3H]cytisine binding. However, the acute inhibitory
      effects of nicotine were not blocked by pretreatment with the nicotinic
      antagonist, mecamylamine. Indeed, at higher doses, mecamylamine also reduced the
      DOI-induced HTR. The data suggest that both nicotine and mecamylamine may be of
      therapeutic potential in the treatment of some symptoms of TS.

PMID- 11513359
TI  - Stability of apomorphine hydrochloride in aqueous sodium bisulphite solutions.
AB  - Apomorphine (Apo), a dopamine receptor agonist used extensively in clinical
      research, is known to be chemically unstable. The authors have used a high
      performance liquid chromatography (HPLC) method to study the long-term stability
      of pharmaceutical preparations of R(-) Apomorphine hydrochloride (ApoHCI) for
      parenteral use. In a concentration of 1 mg/ml, ApoHCI in aqueous solutions of
      sodium metabisulphite (0.125%), kept at 4 degrees and shielded from light, was
      found to be stable for up to six months. On the other hand, solutions of 0.1
      mg/ml were found to decompose after only three weeks, showing extraneous peaks in
      the HPLC. However, the blue-green discoloration, characteristic of Apo
      degradation, was only apparent after six weeks storage. The rapidity of the HPLC
      method used, its reproducibility and sensitivity make it suitable for quality
      control studies of pharmaceutical preparations of ApoHCI intended for clinical
      research.

PMID- 11513360
TI  - Citalopram for social phobia: a clinical case series.
AB  - Social anxiety disorder is a common illness with significant associated
      disability. Serotonin selective reuptake inhibitors (SSRIs) have become first
      line treatment given their improved tolerability; however, there are few reports
      on the use of citalopram. Nine consecutive patients with a primary diagnosis of
      DSM-IV generalized social phobia were prospectively treated with citalopram.
      Citalopram was generally well-tolerated, and seven patients achieved responder
      status. This series of patients improved significantly on all measures. Results
      suggest that citalopram may be a safe and effective treatment for social anxiety
      disorder.

PMID- 11513361
TI  - A successful clonazepam treatment without tolerance in a patient with spontaneous
      oral dyskinesia.
AB  - There has been few reports on the effective treatment for SOD, which is
      phenomenologically similar to TD. A 66-year-old female with SOD was successfully
      treated by CNZ 2 mg/day. Even after one year of continuous treatment, tolerance,
      which is the major problem in the CNZ treatment for TD, did not develop. This
      report suggests that CNZ is effective at least for some patients with SOD.

PMID- 11513362
TI  - Species association among predaceous and phytophagous apple mites (Acari:
      Eriophyidae, Phytoseiidae, Stigmaeidae, Tetranychidae).
AB  - Predator-predator, predator-prey, and prey-prey associations among nine species
      of mites were studied in a plot of 100 'Red Delicious' apple (Malus pumila
      Miller) trees from 1990 to 1997. In 1990, seven-year-old trees were inoculated
      with Panonychus ulmi (Koch), Tetranychus urticae Koch (Acari: Tetranychidae) or
      both, and sprayed with azinphosmethyl (alone or plus endosulfan), or nothing. The
      species Zetzellia mali (Ewing) (Acari: Stigmaeidae), Amblyseius andersoni Chant
      (Acari: Phytoseiidae), Eotetranychus sp., Bryobia rubrioculus (Scheuten) (Acari:
      Tetranychidae), and Aculus schlechtendali Nalepa (Acari: Eriophyidae) were
      already present or immigrated into plots, and Galendromus occidentalis (Nesbitt)
      and Tvphlodromus pyri Scheuten (Acari: Phytoseiidae) were introduced. Yule's V
      association index was used to measure positive, neutral, or negative
      interspecific associations for each species pair, because of its robustness with
      spatially autocorrelated data. We found that pesticide and release treatments did
      not greatly affect the association results, but there were strong seasonal
      differences. Predator-predator associations were the strongest and most
      consistent, showing negative associations in the early and mid seasons, and
      neutral ones in late season. Negative associations of T pyri with other predators
      were the strongest, which is consistent with evidence that this mite can detect
      other predators on a leaf. Predatorprey seasonal associations were mixed, with
      some positive and others negative, with most significant associations occurring
      in the mid season. One prey-prey interaction was positive, again in mid season,
      most likely because of similar habitat preferences.

PMID- 11513363
TI  - Ultrastructure of the integument during moulting of the quiescent tritonymphal
      instar of trombiculid mite Hirsutiella zachvatkini (Acariformes: Trombiculidae).
AB  - The ultrastructure of the integument of the quiescent reduced tritonymph of the
      trombiculid mite Hirsutiella zachvatkini (Schluger) was investigated by means of
      transmission electron microscopy. Mites were investigated daily during the 14-16
      day tritonymphal period (imagochrysalis). This period includes the deutonymphal
      moult (1-3 days), the quiescent tritonymph period (2-4 days), and the
      tritonymphal moult into the adult mite (6-10 days). A distinct recognizable
      feature of the tritonymphal moulting cycle is a sequence of events independent of
      precise time intervals. This process involves partial destruction and
      reorganization of the hypodermis of the previous instar, and formation of a new
      hypodermis of the subsequent instar from islands of rudimentary hypodermal cells.
      The integument of the reduced tritonymph differs greatly from that of both larva
      and active deutonymph and adult. It consists of a simply organized hypodermal
      layer of varying thickness and a thick clear poorly lamellate cuticle with curved
      pore canals, and lacking setae. The epicuticle is very thin and without a clear
      protein layer. The tritonymphal instar as such with its own cuticle situated near
      the hypodermis is encased within the detached covering of the previous active
      deutonymph, and may be considered a calyptostasic and entirely pharate instar.
      There is a tendency for reduced tritonymphal stage to be eliminated from
      ontogenesis and this stage is not homologous to the pupa of insects.

PMID- 11513364
TI  - Male morph determination in Rhizoglyphus echinopus (Acaridae).
AB  - In Rhizoglyphus echinopus (Fumouze and Robin) two male morphs occur:
      heteromorphs, with a thickened and sharply terminated third pair of legs that
      serve as a weapon in intrasexual conflicts, and homeomorphs, with unmodified
      legs. This study investigated the system of male morph determination. No
      significant heritability of male morph was found, but cues emanating from a dense
      colony were found to suppress the production of heteromorphs. Developmental
      plasticity was retained throughout the protonymphal stage. Diet did not influence
      morph expression, but lowered temperature decreased the proportion of
      heteromorphs emerging.

PMID- 11513365
TI  - Cold-hardiness of Dermacentor marginatus (Acari: Ixodidae).
AB  - The cold-hardiness of Dermacentor marginatus using laboratory-reared offspring of
      ticks collected in Germany was characterized. Investigations of unfed stages
      revealed that adult ticks suffered 50% mortality at -10 degrees C after 4-5
      months, but larvae and nymphs suffered mortality within few days, whereas -15
      degrees C was lethal for all stages within a very short period. Larval hatch and
      moulting of engorged larvae and nymphs did not occur at < or = 10 degrees C.
      Embryonic development of eggs with larval hatch was considerably reduced by
      exposure of eggs to < or = 10 degrees C. Engorged females did not lay eggs at <
      or = 10 degrees C, the oviposition capability, however, persisted over 6 months
      at 10 degrees C, 5 months at 5 degrees C, 3 months at 0 degree C and 2 months at 
      10 degrees C without substantial decrease of the oviposition capacity or
      reduction of viable eggs. These results present evidence that unfed adult ticks
      are the ecoepidemiologically most effective stages, which are capable to tolerate
      long and extremely cold winters without substantial impairment of the population
      density. It is also considered that engorged females interrupt their oviposition
      at low and subzero temperatures delaying it for months and so contribute in
      bypassing winter conditions. None of the stages survived supercooling indicating
      that D. marginatus is freeze intolerant. Mean supercooling point (SCP) ranged
      between -26 degrees C in eggs and -12, 6 degrees C in engorged females. Compared
      with eggs, the SCP of the other stages was significantly higher. In conclusion,
      the SCP is considered to have no predictive value in the context with cold
      hardiness.

PMID- 11513366
TI  - Influence of acaricide resistance on cattle-fever tick (Boophilus spp.)
      infestations in semi-arid thornshrublands: a simulation approach.
AB  - Cattle-fever tick (Boophilus microplus and B. annulatus) populations that develop
      acaricide resistance become more difficult to control or eradicate. We used a
      simulation model to assess the direct and indirect effects of interactions among
      season, habitat type, grazing strategy, and acaricide resistance on the ability
      to eradicate Boophilus infestations in semi-arid thornshrublands of Texas, USA.
      Season of infestation appeared to have the strongest effect, with infestations
      begun on 27 September (autumn) tending to die out sooner than those begun on 1
      March (spring) and to remain undetected. Habitat type had the next strongest
      effect, with infestations surviving much longer as canopy cover increased from
      uncanopied buffelgrass (Cenchrus ciliaris) habitats to mesquite (Prosopis
      glandulosa)-canopied grass habitats. Acaricide resistance had a moderate effect;
      as expected, highly resistant tick populations survived longer than those with no
      acaricide resistance. The importance of grazing strategy varied with changes in
      habitat type: as canopy cover increased, infestation duration increased faster
      under continuous grazing than under rotational grazing strategies. Importance of
      grazing strategy also varied with acaricide resistance: detected tick populations
      with no and slight acaricide resistance subjected to acaricide treatments tended
      to survive longer under rotational grazing than continuous grazing, due to
      reduced contact with a treated host. Populations with moderate and high
      resistance behaved more like untreated populations, tending to survive longer
      under continuous, rather than rotational, grazing, because they experienced less
      mortality on a treated host. Assuming acaricide treatments at 2-week intervals
      and maintenance of cattle in infested pastures, results indicate that, for each
      habitat type, infesting ticks have a threshold of acaricide resistance below
      which one can eradicate them faster with continuous grazing than with rotational
      grazing. As canopy cover increases, this threshold appears to shift from high
      resistance (in grass) to slight resistance (in mesquite).

PMID- 11513367
TI  - Potential role of parasitism in the evolution of mutualism in astigmatid mites:
      Hemisarcoptes cooremani as a model.
AB  - Phoresy is a symbiotic interaction that results in dispersal, benefiting the
      relocated organism without negatively impacting the phoretic host. It has long
      been considered that phoresy among astigmatid mites is somehow an intermediate
      precursor to the evolution of parasitism within the group. In astigmatid mites,
      only the heteromorphic deutonymph (hypopode) participates in phoretic dispersal,
      and the plesiomorphic hypopode may be the key to understanding the dynamics of
      the evolution of that parasitism. Hypopodes of Hemisarcoptes cooremani (Acari:
      Acariformes) and their phoretic beetle host Chilocorus cacti (Coleoptera:
      Coccinellidae) have become the experimental focus for studies concerned with the
      potential forces that influence the transition of a free-living life style into
      various coevolved relationships. Previous radiolabeling studies applied to H.
      cooremani and C. cacti determined that hypopodes of H. cooremani acquired
      resources from adults of C. cacti while in transit, negating the paradigm that
      the heteromorphy was purely phoretic. To further probe this relationship, we
      tested whether materials could be passed from the mites to their hosts. We report
      here a study using a tritium radiolabel, which indicated that beetles also
      acquire resources from the hypopodes. These results have implications for
      understanding the complex relationship between H. cooremani and C. cacti. We
      propose that this relationship should now correctly be defined as mutualistic
      (not phoretic) and develop a general model for the potential role of parasitism
      in the evolution of mutualism among the Astigmata.

PMID- 11513368
TI  - A general population comparison of the Composite International Diagnostic
      Interview (CIDI) and the Schedules for Clinical Assessment in Neuropsychiatry
      (SCAN).
AB  - BACKGROUND: In psychiatric surveys of the general population, there has been
      considerable discrepancy between diagnoses obtained by fully structured
      interviews and those established by systematic semi-structured clinical
      evaluation. The Composite International Diagnostic Interview (CIDI) is an example
      of the first type of interview widely used in general population surveys. We
      compared its performance in diagnosing current depressive and anxiety disorders
      with the Schedules for Clinical Assessment in Neuropsychiatry (SCAN), a semi
      structured diagnostic interview administered by clinically trained interviewers.
      METHODS: Household addresses in Leicestershire, UK, were randomly sampled and 860
      adults were screened with the Revised Clinical Interview Schedule. Adults with
      too few symptoms to fulfil diagnostic criteria for study disorders were excluded
      to increase the proportion re-interviewed who met such criteria. Repeat
      diagnostic interviews with the CIDI and SCAN, ordered randomly, were sought from
      eligible screen positive respondents. Recalibrated CIDI prevalence estimates were
      derived from the SCAN classification using Bayesian statistics. RESULTS:
      Concordance ranged between 'poor' and 'fair' across almost all types of study
      disorders, and for co-morbidity. Concordance was somewhat better for severity of
      depression and when lower diagnostic thresholds were used for depression.
      Interview order effects were suggested with lower concordance when CIDI followed
      SCAN. Recalibration reduced the prevalence of depressive or anxiety disorder from
      9.0 to 6.2%. CONCLUSIONS: Community psychiatric surveys using structured
      diagnostic interview data must be interpreted cautiously. They should include an
      element of clinical re-appraisal so findings can be adjusted for estimation
      differences between fully structured and clinical assessments.

PMID- 11513369
TI  - The royal free interview for spiritual and religious beliefs: development and
      validation of a self-report version.
AB  - BACKGROUND: Spiritual beliefs are rarely considered in psychological or medical
      publications. We recently published the psychometric properties of an interview
      designed to measure religious and spiritual belief. In this study, we aimed to
      develop this instrument further as a self-report questionnaire and to make it
      more comprehensive by including measurement of spiritual experiences in addition
      to faith or intellectual assent. METHODS: Based on extensive discussion with
      colleagues, advice from users of the interview and comments from respondents, a
      self-report format was designed. We then evaluated the final format of the
      questionnaire in terms of (1) patterns of response and demographic predictors of
      beliefs; (2) test-retest reliability and internal consistency; (3) criterion and
      internal validity; and (4) the nature of spiritual experiences and their
      relationship to beliefs and strength of beliefs. RESULTS: Two hundred and ninety
      seven people took part in the validity and reliability tests of the
      questionnaire. Criterion validity, predictive validity, internal consistency and
      test-retest reliability were acceptably high. The instrument consistently
      differentiated between people with high and low spiritual beliefs. CONCLUSIONS:
      This instrument is brief and simple to complete. We would recommend that measures
      of religious and/or spiritual belief like this be more widely applied in health
      services research as they evaluate aspects of people's lives that go somewhat
      further than health status or quality of life.

PMID- 11513370
TI  - The Liebowitz Social Anxiety Scale: a comparison of the psychometric properties
      of self-report and clinician-administered formats.
AB  - BACKGROUND: The clinician-administered version of the Liebowitz Social Anxiety
      Scale (LSAS-CA) is a commonly used assessment device for the evaluation of social
      anxiety disorder and has been shown to have strong psychometric characteristics.
      Because of its apparently straightforward rating format and potential savings in
      time and effort, interest in the use of the LSAS as a self-report (LSAS-SR)
      measure has increased, and the LSAS-SR has been used in a number of studies.
      However, the psychometric properties of the LSAS-SR have not been well
      established. METHODS: This study examined the psychometric properties of the LSAS
      SR in comparison to the LSAS-CA in a sample of 99 individuals with a primary
      diagnosis of social anxiety disorder and 53 individuals with no current
      psychiatric disorder. RESULTS: There was little difference between the two
      versions of the LSAS on any scale or subscale score. Both forms were internally
      consistent and the subscale intercorrelations for the two forms were essentially
      identical. Correlations of each LSAS-SR index with its LSAS-CA counterpart were
      all highly significant. Finally, the convergent and discriminant validity of the
      two forms of the LSAS was shown to be strong. CONCLUSION: Results of this study
      suggest that the self-report version of the LSAS compares well to the clinician
      administered version and may be validly employed in the assessment of social
      anxiety disorder.

PMID- 11513371
TI  - Epidemiology of unexplained fatigue and major depression in the community: the
      Baltimore ECA follow-up, 1981-1994.
AB  - BACKGROUND: Fatigue is a common, non-specific, subjective symptom associated with
      several medical and psychiatric illnesses. The purpose of this investigation was
      to explore further the epidemiology of unexplained fatigue in the general
      population and the relationship between fatigue and depression. METHODS: The
      design was a prospective population-based study. Subjects included community
      dwelling adults who were participants of the Baltimore sample of the
      Epidemiologic Catchment Area Program in 1981 and who were reinterviewed 13 years
      later. Lay interviewers using the Diagnostic Interview Schedule interviewed
      subjects. RESULTS: Number of somatization symptoms and history of a dysphoric
      episode at baseline were the two strongest predictors of both new onset of
      fatigue as well as recurrent/chronic fatigue over the 13-year follow-up interval.
      In addition, individuals who reported a history of unexplained fatigue at
      baseline as well as during the follow-up, were at markedly increased risk for new
      onset major depression as compared to those who never reported such fatigue, (RR
      = 28.4, 95% CI) (11.7, 68.0). Similarly, respondents who developed new fatigue or
      had remitted fatigue after 1981 were also at increased risk for developing major
      depression. CONCLUSIONS: Somatization was the strongest predictor of both new and
      chronic fatigue with unknown cause. In addition, fatigue was both predictive and
      a consequence of the depression syndrome.

PMID- 11513372
TI  - Regional variation in the incidence of schizophrenia in Finland: a study of birth
      cohorts born from 1950 to 1969.
AB  - BACKGROUND: We investigated whether there is regional variation in the incidence
      of schizophrenia and if so. whether it is caused by urban-rural differences,
      larger spatial clustering, or both. To control for the effect of migration, we
      examined regional variation in the incidence according to place of birth.
      METHODS: Finnish birth cohorts born from 1950 to 1969 were followed in the
      National Hospital Discharge Register from 1969 until 1991, and all cases of
      schizophrenia (ICD-8 or ICD-9 295) were identified (N = 14828). Forty-eight of
      the 559 municipalities were classified as urban and 25% of the Finnish population
      lived in these municipalities in 1960. For the analysis of spatial clustering,
      municipalities were grouped into 57 functional small-areas. We used Poisson
      regression model with the number of births of individuals who later developed
      schizophrenia as a response variable, and place of birth (urban/rural), birth
      cohort (1950-54, 1955-9, 1960-64, and 1965-9), functional small-area units, and
      sex as response variables. RESULTS: The incidence was slightly higher among the
      rural-born in the oldest birth cohort. In the other cohorts, it was higher among
      the urban-born, and the difference between urban and rural born increased in the
      youngest cohorts. Significant spatial clustering of schizophrenia was observed in
      eastern Finland. CONCLUSIONS: Urban birth is a risk factor for schizophrenia in
      Finland in cohorts born since 1955. However, genuine spatial clustering of
      schizophrenia in eastern Finland was also observed, possibly caused by genetic
      isolation.

PMID- 11513373
TI  - Social roles and the gender difference in rates of the common mental disorders in
      Britain: a 7-year, population-based cohort study.
AB  - BACKGROUND: It is not known why the most common mental disorders (CMD), anxiety
      and depression, are more prevalent among women. This gradient has not been
      explained by differences in the number or type of social roles occupied by men
      and women. Given the dearth of longitudinal studies, these negative findings
      could reflect reverse causality, if men with CMD relinquish social roles more
      readily than women. METHODS: Cohort study using data from the first seven
      (annual) waves of the British Household Panel Survey. The prevalence of CMD was
      assessed using the General Health Questionnaire (GHQ), 12 months after
      ascertaining occupancy of five social roles. Of 12379 participants aged 16-70,
      9947 completed the GHQ on at least two consecutive occasions, resulting in 44139
      paired observations. Random effects models adjusted for the correlation of
      repeated measures and for baseline GHQ score. RESULTS: The odds ratio for the
      gender difference in the future prevalence of CMD (adjusted for baseline GHQ
      score) was 192 (95% CI 1.75-2.10). Neither the number or type of social roles
      occupied, nor socio-economic status explained the gender difference in these
      conditions (adjusted OR 182, 95% CI 1.66-1.99). While CMD at baseline was
      associated with a subsequent reduction in social role occupancy, this did not
      vary between men and women. CONCLUSIONS: Gender differences in CMD were not
      explained by differences in the number or type of social roles occupied by men
      and women, or by reverse causality. Future studies should consider
      characteristics of social roles, such as demand, control and reward.

PMID- 11513374
TI  - Effects of olanzapine on cerebellar functional connectivity in schizophrenia
      measured by fMRI during a simple motor task.
AB  - BACKGROUND: According to current theories, schizophrenia results from altered
      connectivity in brain circuits for fundamental cognitive operations.
      Consequently, the poorly understood mechanisms of neuroleptic treatment may be
      explainable by altered functional interactions within such networks. The
      'cognitive dysmetria' model hypothesizes that one key structure in these circuits
      is the cerebellum. To investigate the effects of olanzapine on cerebellar
      functional connectivity (CFC), a seed-voxel correlation analysis (SVCA) was used
      in a functional magnetic resonance imaging (fMRI) study of a simple finger
      tapping task. METHODS: fMRI scans were obtained from six schizophrenic patients
      under both drug-free and olanzapine-treated conditions and from a matched control
      group of six healthy subjects at corresponding time points. SVCAs were performed
      for anatomically and functionally standardized seed voxels in the anterior
      cerebellum. SVCA results were then processed by three different randomization
      analyses. RESULTS: The analyses revealed that olanzapine caused widespread
      changes of CFC, including prominent changes in prefrontal cortex and mediodorsal
      thalamus. Significant changes in motor structures were found after subtractions
      within both groups and may thus indicate repetition effects rather than drug
      effects. Olanzapine 'normalized' the patients' CFC patterns for the right, but
      not for the left cerebellum. CONCLUSION: Even for a simple motor task, olanzapine
      affects functional interactions between the cerebellum and many non-motor brain
      regions, including elements of the 'cognitive dysmetria' circuit. Altogether, our
      findings suggest that olanzapine has a stronger differential effect on neural
      activity in prefrontal cortex and thalamus than in motor structures.

PMID- 11513375
TI  - Aberrant brain activation following motor skill learning in schizophrenic
      patients as shown by functional magnetic resonance imaging.
AB  - BACKGROUND: Motor skill learning may be impaired in schizophrenia. While
      functional brain imaging studies have shown reduced activation during motor task
      performance in schizophrenic patients, brain activity changes with motor skill
      learning in these patients have not been studied by functional imaging. METHODS:
      A sequential complex motor task involving the right hand was performed by nine
      medicated schizophrenic patients and 10 age-matched healthy controls. Functional
      magnetic resonance images were obtained using a gradient echo, echoplanar imaging
      (EPI) pulse sequence before and after 1 week of training in performing the task.
      RESULTS: Bilaterally, patients showed significantly less blood oxygenation level
      dependent (BOLD) signal response in the premotor area (PMA) before beginning
      motor training than controls. BOLD signal response increased in the left PMA of
      schizophrenic patients after 1 week of motor training; in contrast, the signal
      decreased in the left PMA of control subjects. Training effects concerning the
      number of finger movement sequences achieved did not differ between groups. Daily
      neuroleptic dose did not significantly affect changes with training in BOLD
      signal response in the PMA. CONCLUSIONS: These preliminary results suggest that
      schizophrenic patients have dysfunction of neural networks in areas including the
      PMA that are involved in executing a complex motor task. In terms of brain
      activity, motor learning may be less efficient or slower in the patients than in
      healthy subjects.

PMID- 11513376
TI  - Missing the forest for the trees? Deficient memory for linguistic gist in
      obsessive-compulsive disorder.
AB  - BACKGROUND: Patients with obsessive-compulsive disorder (OCD) exhibit recall
      deficits on word learning tasks, mediated by their failure to detect semantic
      connections among the words. METHODS: In the present experiment, using methods
      devised by Bransford & Franks (1971), we tested whether this encoding problem
      impairs their extraction of gist from complex linguistic material. RESULTS:
      Consistent with our hypothesis, OCD patients extracted less gist from related
      sentences than did healthy participants. The groups did not differ in recognition
      memory for individual sentences or in criterion for affirming previously
      encountered sentences as 'old', as evinced by signal detection indices of memory
      sensitivity (d') and response bias (beta), or in recognition memory confidence.
      CONCLUSIONS: These data provide further evidence that OCD patients exhibit less
      reliance on organizational strategies than do healthy control participants. These
      data are consistent with neuropsychological research suggestive of prefrontal
      executive problems in OCD.

PMID- 11513377
TI  - A deficit in attentional set-shifting of violent offenders.
AB  - BACKGROUND: Recent brain imaging studies suggest that proneness to violence and
      antisocial behaviour may be associated with dysfunction of the prefrontal cortex.
      The present study. therefore, examined aspects of prefrontally guided executive
      functions in a group of criminal violent men. METHODS: Violent offenders
      undergoing forensic psychiatric examination by court order undertook computerized
      tasks for planning, visual working memory and attentional set-shifting from the
      Cambridge Neuropsychological Test Automated Battery. Their performance was
      compared to that of subjects with marginal mental retardation and normal
      controls. RESULTS: Violent offenders performed well on tasks for spatial and
      figurative working memory, as well as on a test for planning. A marked impairment
      was observed in the attentional set-shifting task: offenders made significantly
      more errors than the other groups when required to shift attention from one
      perceptual dimension to another. Reversal learning was also deficient.
      Correlational analyses within the offender group revealed that poor performance
      on the perceptual shift problem was associated with fewer errors in tasks for
      working memory and planning. CONCLUSIONS: The present results suggest that
      violent offenders show dual impairments in inhibitory cognitive control. First,
      they are deficient in shifting attention from one category to another. Secondly,
      the ability to alter behaviour in response to fluctuations in the emotional
      significance of stimuli is compromised. These deficits might constitute cognitive
      reflections of the biological prefrontal alterations observed in this group of
      people.

PMID- 11513378
TI  - Abnormal executive function in attention deficit hyperactivity disorder: the
      effect of stimulant medication and age on spatial working memory.
AB  - OBJECTIVE: This study sought to examine the factors associated with spatial
      working memory and the use of strategies to impairments in spatial working memory
      in children with attention deficit hyperactivity disorder (ADHD). The
      developmental trajectories for spatial working memory in medicated and medication
      naive children with ADHD were investigated. In addition, the effect of
      psychostimulant medication on deficits in spatial working memory was examined.
      METHOD: A cross-sectional study compared performance between 21 psychostimulant
      medicated children with ADHD, 27 medication naive children with ADHD and 26
      matched control subjects on computerized tests of spatial memory and spatial
      working memory. RESULTS: Compared with the controls, performance in medication
      naive children with ADHD was significantly worse on the spatial working memory
      task. There was no difference in performance between the medicated children with
      ADHD and the control subjects on this same task, despite the ongoing symptoms of
      ADHD in the former group. The pattern of normal and abnormal performance in the
      ADHD groups was age-independent. CONCLUSIONS: Deficits in executive functions
      related to spatial working memory do occur in children with ADHD, although the
      magnitude of these deficits is not related to the child's age or the level of
      ADHD symptoms. These deficits were not present in the current sample of children
      who were receiving psychostimulant medication.

PMID- 11513379
TI  - An exploration of evolved mental mechanisms for dominant and subordinate
      behaviour in relation to auditory hallucinations in schizophrenia and critical
      thoughts in depression.
AB  - BACKGROUND: Mental mechanisms have evolved to enable animals (and humans) to be
      able to function in various social roles. It is suggested that the nature and
      functions of the mental mechanisms that enable animals to act as a hostile
      dominant or threatened-subordinate can be distinguished. It is further suggested
      these can be internally activated and 'play off' against each other, such that a
      person 'attacks' themselves and then responds to their own internal attacks with
      subordinate defences. Hence, a depressed person can submit, feel defeated,
      belittled, beaten down, or want to run away (escape) from their own self
      attacking thoughts, while psychotic voice hearers can feel similarly to their
      hostile voices. Such internal interactions may relate to depression in both
      psychotic voice hearers and depressed people. METHOD: A group of 66 voice hearers
      with a diagnosis of schizophrenia and 50 depressed patients were compared on a
      series of self-report questionnaires measuring the power of hostile self-directed
      thoughts/voices and the activation of defensive responses, especially
      fight/flight. RESULTS: We present evidence that schizophrenic, malevolent voice
      hearers and self-critical depressed people experience their hostile, internally
      generated voices/thoughts as powerful, dominating and controlling (i.e. have
      typical characteristics of a hostile dominant). Moreover, these voices/thoughts
      activate evolved subordinate defences such as fight/flight and these are
      associated with depression in both depression and schizophrenia. CONCLUSION:
      Conceptualizing aspects of depressed and psychotic thinking as relating to
      evolved mental mechanisms, which are role serving, but can internally play off
      against each other, may open new ways of investigating certain aspects of severe
      pathologies.

PMID- 11513380
TI  - Neuroticism as a risk factor for schizophrenia.
AB  - BACKGROUND: Neuroticism has been shown to increase the risk of depression whereas
      extraversion is associated with a reduction of risk. These personality traits
      play a central role in aetiological theories of affective disorder but their role
      in schizophrenia is unclear. In this study, the risk for schizophrenia associated
      with neuroticism and extraversion was examined and quantified. METHODS:
      Neuroticism and extraversion rated at the age of 16 years were examined in
      relation to adult schizophrenia in a national birth cohort of 5362 individuals.
      RESULTS: Neuroticism increased the risk of later schizophrenia independent of the
      level of affective symptoms in adult life (odds ratio over three levels: 1.93,
      95% CI 1.09-3.43), whereas extraversion reduced the risk (OR: 044, 95% CI 0.23
      0.84). CONCLUSIONS: Depression and schizophrenia may share personality risk
      increasing and risk-reducing factors. Coping styles associated with particular
      personality traits may determine whether isolated symptoms progress to full-blown
      illness.

PMID- 11513381
TI  - Full-spectrum fluorescent lighting: a review of its effects on physiology and
      health.
AB  - BACKGROUND: Full-spectrum fluorescent lighting (FSFL) has been credited with
      causing dramatic beneficial effects on a wide variety of behaviours, mental
      health outcomes and physical health effects, as compared to other fluorescent
      lamp types. These effects are hypothesized to occur because of similarity between
      FSFL emissions and daylight, which is said to have evolutionary superiority over
      other light sources. METHOD: This review, covering the period 1941-1999,
      critically considers the evidence for direct effects of FSFL through skin
      absorption as well as indirect effects on hormonal and neural processes.
      CONCLUSIONS: Overall, the evidence does not show dramatic effects of fluorescent
      lamp type on behaviour or health, neither does it support the evolutionary
      hypothesis.

PMID- 11513382
TI  - Psychopathology, childhood sexual abuse and other childhood adversities: relative
      links to subsequent suicidal behaviour in the US.
AB  - BACKGROUND: Research shows that psychopathology, child sexual abuse and other
      childhood adversities are risk factors for suicide. However, few have
      investigated their joint and independent roles in the pursuit of a reliable,
      predictive model of suicidal behaviour. METHODS: Data are from the National
      Comorbidity Survey (N = 5877), a nationally representative study of prevalence,
      risk factors, and social consequences of psychiatric disorders in the US.
      Discrete time survival analysis and population attributable risk methodologies
      were utilized. RESULTS: Among those sexually abused as children, odds of suicide
      attempts were 2-4 times higher among women and 4-11 times higher among men,
      compared with those not abused, controlling for other adversities. Odds ratios
      were reduced but most remained statistically significant after adjusting for
      lifetime psychiatric illnesses preceding suicide attempts. In the same predictive
      equation, 79% of serious suicide attempts among women could be attributed to
      psychiatric disorders while 12% was attributable to rape and 7% to molestation.
      The highest probability of a first attempt was during early adolescence for those
      who were sexually abused and had a lifetime disorder, but it was 8-12 years older
      for those sexually abused without any disorders. CONCLUSIONS: In the US, a strong
      association exists between child sexual abuse and suicidal behaviour, mediated by
      psychopathology. There is a substantial proportion of suicide risk attributable
      to child sexual abuse beyond the presence of psychopathology and other
      adversities. From a clinical standpoint, abuse survivors represent a high-risk
      population for suicidal behaviour. Further research into this preventable
      antecedent of suicide attempts is necessary.

PMID- 11513383
TI  - The efficacy of problem-solving treatments after deliberate self-harm: meta
      analysis of randomized controlled trials with respect to depression, hopelessness
      and improvement in problems.
AB  - BACKGROUND: Brief problem-solving therapy is regarded as a pragmatic treatment
      for deliberate self-harm (DSH) patients. A recent meta-analysis of randomized
      controlled trials (RCTs) evaluating this approach indicated a trend towards
      reduced repetition of DSH but the pooled odds ratio was not statistically
      significant. We have now examined other important outcomes using this procedure,
      namely depression, hopelessness and improvement in problems. METHOD: Six trials
      in which problem-solving therapy was compared with control treatment were
      identified from an extensive literature review of RCTs of treatments for DSH
      patients. Data concerning depression, hopelessness and improvement in problems
      were extracted. Where relevant statistical data (e.g. standard deviations) were
      missing these were imputed using various statistical methods. Results were pooled
      using meta-analytical procedures. RESULTS: At follow-up, patients who were
      offered problem-solving therapy had significantly greater improvement in scores
      for depression (standardized mean difference = -0.36; 95% CI -0.61 to -0.11) and
      hopelessness (weighted mean difference =-3.2; 95% CI -4.0 to -2.41), and
      significantly more reported improvement in their problems (odds ratio = 2.31; 95%
      CI 1.29 to 4.13), than patients who were in the control treatment groups.
      CONCLUSIONS: Problem-solving therapy for DSH patients appears to produce better
      results than control treatment with regard to improvement in depression,
      hopelessness and problems. It is desirable that this finding is confirmed in a
      large trial, which will also allow adequate testing of the impact of this
      treatment on repetition of DSH.

PMID- 11513385
TI  - Characterisation of non-condensable sulphur containing gases from Kraft pulp
      mills.
AB  - This paper describes work performed on the sampling and analysis of non
      condensable gases (NCG) emitted from diffuse sources of a Portuguese Kraft pulp
      mill, which is the background information for a NCG collection, treatment and
      disposal system. The variability found in the composition of the gaseous
      compounds showed the existence of gaseous streams other than typical total
      reduced sulphur (TRS) compounds as usually described. From the measured TRS
      concentrations and the gas flow rate from each source it was possible to
      calculate the emission flow rate, E, of each source. These emission flow rates
      were then divided into three categories which are quite useful to identify
      significant sources and to choose abatement techniques. The methodology presented
      allows for a precise quantification of sources so that similar emissions can be
      grouped for treatment purposes. Sources with an emission flow rate bigger than 1
      kg/h have a marked effect on the overall TRS emissions of the mill, as they are
      major contributors. It was also found that a new analytical procedure using
      Restek columns is more easy to use and overcomes operational problems noticed
      previously, namely a run time of 20-25 min instead of 50-60 min.

PMID- 11513384
TI  - Panic syndromes in a population-based sample of male and female twins.
AB  - BACKGROUND: The risk for panic disorder (PD) is substantially increased in
      relatives of probands with PD. Prior literature provides only limited information
      about the degree to which this increase is due to genetic factors or family
      environment. METHODS: In personal interviews with both members of 3194 twin
      pairs, we assessed the lifetime history of lifetime panic attacks and PD. Twin
      resemblance was assessed by tetrachoric correlation and single and multiple
      threshold biometrical model fitting. RESULTS: As fully syndromal PD, by DSM-III-R
      criteria, was too rare to analyse usefully we examined four other dichotomous
      definitions of increasing stringency: panic probe and very broad, broad and
      intermediate PD. For all four definitions and for the multiple threshold
      analyses, the best-fit model indicated that twin resemblance was due solely to
      genetic factors with a moderate heritability (33-43%). For the broad and
      intermediate dichotomous definitions of PD, however, a model with twin
      resemblance due to familial-environmental factors fit nearly as well. No gender
      effects were seen on the genetic risk factors for these PD-like syndromes.
      CONCLUSION: Even with large epidemiological samples of twins, studying disorders
      as uncommon as PD is problematical. Despite these difficulties, our results
      suggest that: (i) narrowly and broadly defined PD are probably on the same
      continuum of liability; (ii) twin resemblance for these PD-like syndromes is
      likely due largely to genetic factors with a moderate level of heritability
      although a contribution of familial-environmental factors cannot be excluded,
      and, (iii) the same familial risk factors impact. to a similar degree, on the
      liability to PD in males and females.

PMID- 11513387
TI  - Municipal landfill leachate-soil interactions: a kinetic approach.
AB  - On investigating the effects of municipal landfill leachates on soils, it is
      found that the adsorption of landfill leachate constituents creates a "new" soil
      surface able to enhance heavy metal uptake. In particular, the treatment of soil
      with the total leachates led to an increase in its metal retention capability
      that was much higher than for each individual fraction. Results show that the
      leachate sorption on soil is regulated by the presence of leachate constituents
      with low molecular weight cut-off since these fractions are able to "accelerate"
      the sorption of higher molecular weight fractions. The rapidly sorbed lower
      molecular weight fractions create a different soil surface that is able to
      accommodate the high molecular weight constituents.

PMID- 11513386
TI  - Highly concentrated phenolic wastewater treatment by the photo-Fenton reaction,
      mechanism study by FTIR-ATR.
AB  - Phenol degradation by Photo-Fenton reaction has been studied in highly
      concentrated wastewaters and most intermediate species have been identified by
      Fourier Transform IR-Spectroscopy with ATR device. During the photodegradation of
      highly concentrated phenol solutions, the formation of dissolved and precipitate
      tannin has been observed. The possibility of a Fe3+-Pyrogallol complex formation,
      previous to the tannin formation, has been proposed too. The complex formation
      involving Fe3+ ions could be related to the observed Photo-Fenton activity
      decrease. Tannin formation inhibits the complete mineralization of phenol because
      *OH radicals attack will produce further condensation steps and the polymer size
      increase. This fact limits the applicability of the process for highly
      concentrated phenolic wastes mineralization. However, the tannin precipitation
      allows its separation from the solution by conventional filtration, and reduction
      of the corresponding dissolved organic carbon. These observations have been
      proved from the identification of primary degradation products, catechol and
      hydroquinone. Catechol is considered to be the first step for the formation of
      tannins. Degradation process for phenol, catechol and hydroquinone have been
      monitored by total organic carbon (TOC) measurements along the reaction time
      span. From these results, a global mechanism for the Photo-Fenton degradation of
      phenol is proposed.

PMID- 11513388
TI  - Suitability of dye-clay complexes for removal of non-ionic organic compounds from
      aqueous solutions.
AB  - Aqueous sorption of phenol, atrazine and naphthalene was measured on complexes
      formed from Na-montmorillonite (Fischer bentonite) and the organic cationic dyes
      crystal violet and rhodamine-B. Sorption isotherms were found to be non-linear.
      This agrees well with the rigid nature of the dye-clay organic coverage, which
      provides a finite surface for adsorption. High values of organic carbon
      normalized distribution coefficients reached 20,000-25,000 for atrazine on
      rhodamine-B-montmorillonite, 7000 for atrazine on crystal violet-montmorillonite,
      and 1500 for phenol on crystal violet-montmorillonite. As such, dye-clays may
      significantly extend the variety of organoclay sorbents that effectively reduce
      aqueous concentrations of non-ionic organic compounds.

PMID- 11513389
TI  - Biodegradation of quinoline by gel immobilized Burkholderia sp.
AB  - Burkholderia sp, a gram-negative, rod-shaped, aerobe, capable of degrading
      quinoline was immobilized in calcium alginate gel beads and used for degradation
      of quinoline in aqueous solution in the reactor. The optimal conditions for
      immobilization of the microorganism, such as alginate concentration, calcium ion
      concentration, initial cell loading, hardening time and bead size, were
      determined with a view to improving the quinoline degradation rate. The
      characteristics of quinoline degradation by immobilized microbial cells were
      investigated. The repeated use of immobilized cells for quinoline degradation was
      performed and the results revealed that the bioactivity of immobilized cells was
      stable over 100 h in the repeated batch cultivation for quinoline degradation.

PMID- 11513390
TI  - Denitrification with acrylamide by pure culture of bacteria isolated from
      acrylonitrile-butadiene-styrene resin manufactured wastewater treatment system.
AB  - Acrylamide is widely used in industrial applications as cement binder and
      solidification agent. Due to its carcinogenicity and toxicity, discharge of
      acrylamide to the natural water and soil systems may lead to an adverse
      environmental impact on water quality and thus endanger public health and
      welfare. This study attempts to isolate and identify the denitrifying bacteria,
      which utilize acrylamide as the substrate from the acrylonitrile-butadiene
      styrene resin manufactured wastewater treatment system. The performance of the
      denitrifying bacteria for treating different initial acrylamide concentrations
      was also investigated under aerobic and anaerobic conditions. The test results
      indicated that the Pseudomonas stutzeri could remove acrylamide at concentrations
      below 440 mg/l under aerobic conditions. The acrylic acid and ammonia
      intermediates were used as carbon and nitrogen sources, respectively. However, P.
      stutzeri did not show the capability of metabolizing acrylonitrile under aerobic
      conditions. Furthermore, the P. stutzeri could utilize both acrylamide and
      acrylic acid in the presence of nitrate (denitrification) and acrylamide could be
      removed completely from the wastewater.

PMID- 11513391
TI  - Regulating colored textile wastewater by 3/31 wavelength ADMI methods in Taiwan.
AB  - The wastewater from textile dyeing facilities is difficult to treat
      satisfactorily because of high compositional variability and high color
      intensity. To reduce colored effluents discharged into watercourses, the
      government of Taiwan adopted the Effluent True Color Standard in 1998. The true
      color discharge limit is 400 American Dye Manufactures Institute (ADMI) units.
      The adopted analytical method is the ADMI Tristimulus Filter Method (3 wavelength
      (WL) method), and the 31 WL ADMI method might be also adopted as an alternative
      for color value measurement. The refractory nature of textile dyes and the
      introduction of this new regulation present an environmental challenge to the
      Taiwanese textile industry. The main objectives of this study were to (1)
      evaluate the efficacy of current wastewater treatment systems for controlling the
      colored textile wastewater discharges, and (2) evaluate the correlations between
      3 and 31 WL ADMI methods. Ten representative textile wastewater treatment
      facilities employing biological and chemical coagulation treatment technologies
      were selected to perform a 10-consecutive-day effluent sampling and analysis.
      Results show that a significant difference between 3 and 31 ADMI methods was
      observed. These two ADMI methods cannot be substituted for each other, and the
      discharge standard should be determined based on the selected testing method.
      Investigation results also suggest that the commonly used wastewater treatment
      technology (biological + chemical coagulation) fails to effectively remove dye
      from the colored textile wastewater. Sodium hypochlorite (NaOCl) addition was
      applied by most facilities as the temporary post-polishment step to comply with
      the color discharge standard.

PMID- 11513393
TI  - Synthetic fuel for imitation of municipal solid waste in experimental studies of
      waste incineration.
AB  - Synthetic fuel is prepared to imitate municipal solid waste (MSW) in experimental
      studies of incineration processes. The fuel is composed based on the
      Environmental Protection Agency reports on the materials contained in MSW.
      Uniform synthetic fuel pellets are prepared using available and inexpensive
      components including newsprint, hardwood mulch, low density polyethylene, iron,
      animal feed, sand, and water to imitate paperbound, wood, yard trimming, plastic,
      metal, food wastes, and other materials in MSW. The synthetic fuel preparation
      procedure enables one to reproduce and modify the fuel for a wide range of
      experiments in which the mechanisms of waste incineration are addressed. The fuel
      is characterized using standard ASTM tests and it is shown that its parameters,
      such as combustion enthalpy, density, as well as moisture, ash and fixed carbon
      contents are adequate for the representation of municipal solid waste. In
      addition, chlorine, nitrogen, and sulfur contents of the fuel are shown to be
      similar to those of MSW. Experiments are conducted in which the synthetic fuel is
      used for operation of a pilot-scale incinerator research facility. Steady-state
      temperature operation regimes are achieved and reproduced in these experiments.
      Thermodynamic equilibrium flame conditions are computed using an isentropic one
      dimensional equilibrium code for a wide range of fuel/air ratios. The molecular
      species used to represent the fuel composition included cellulose, water, iron,
      polyethylene, methanamine, and silica. The predicted concentrations of carbon
      monoxide, nitric oxides, and oxygen in the combustion products are compared with
      the respective experimental concentrations in the pilot-scale incinerator
      exhaust.

PMID- 11513392
TI  - Leaching of 2,4-D from a soil in the presence of beta-cyclodextrin: laboratory
      columns experiments.
AB  - This study reports on the effect of the presence of beta-cyclodextrin (beta-CD)
      on the adsorption and mobility of the pesticide 2,4-dichlorophenoxyacetic acid
      (2,4-D) through soil columns. The previous application of beta-CD to the soil
      produced a retarded leaching of 2,4-D through the soil column, due probably to
      herbicide adsorption on the soil through beta-CD adsorbed. However, the
      application of beta-CD solution to the soil column where 2,4-D had been
      previously adsorbed, led to the complete desorption of the herbicide, due to the
      formation of water-soluble 1:1 inclusion complexes between 2,4-D and beta-CD.
      Beta-CD can be viewed as a microscopic organic-phase extractant. It can be an
      advantage to remove from soil pesticides which are able to form inclusion
      complexes with cyclodextrins, making them possible candidates for use in in situ
      remediation efforts.

PMID- 11513394
TI  - Pyrene biodegradatin in aqueous solutions and soil slurries by Mycobacterium PYR
      1 and enriched consortium.
AB  - To better understand complex bioavailability issues, pyrene degradation was
      examined in aqueous and soil slurry solutions using pure Mycobacterium sp. PYR-1
      and a microbial consortium. The intrinsic rates of the aqueous pyrene degradation
      were very similar, 1.3 x 10(-9) microg pyrene/CFU-h for Mycobacterium sp. PYR-1
      and 1.1 x 10(-9) microg pyrene/CFU-h for the consortium. Rates were much lower
      with the soil-slurry experiments, ranging from 1.2 x 10(-12) to 7.8 x 10(-10)
      microg/CFU-h, depicting the strong negative effects of soils on bioavailability.
      Supernatants from the slurry experiments were found to increase the aqueous-phase
      pyrene solubility significantly. Pyrene solubility was increased from 120.5 to
      over 230 microg/l. However, the linear adsorption constants of pyrene on the soil
      were reduced.

PMID- 11513395
TI  - Photocatalytic activity of TiO2 films grown on different substrates.
AB  - Titanium dioxide films were prepared on glass, indium-tin oxide (ITO) glass and p
      type monocrystalline silicon and studied for the photocatalytic degradation of
      rhodamine B in an aqueous medium. Raman, AFM, and XPS spectroscopic
      investigations of these films indicated that microstructure of titanium oxide
      films were greatly affected by the substrate materials. Rutile was confirmed to
      be easily formed on the surface of ITO glass, and TiO2 tended to grow as closely
      packed particles that were elongated strips with an average size of 20 nm, and
      had lovely contrast with the perfectly round particles grown on p-type
      monocrystalline silicon. Charge transfer between the film and silicon substrate
      was verified by surface photovoltage spectra. This may be the real reason why the
      films grown on ITO glass and silicon substrates exhibit higher photocatalytic
      reactivity than the film on glass substrate. Moreover, the different surface
      properties also seem to be responsible for the different activity.

PMID- 11513396
TI  - Bioleaching of heavy metals from sediment: significance of pH.
AB  - Bioleaching process, which causes acidification and solubilization of heavy
      metals, is one of the promising methods for removing heavy metals from
      contaminated sediments. The solubilization of heavy metals from contaminated
      sediments is governed by the sediment pH. In the present study, the significance
      of pH in bioleaching of heavy metals from contaminated sediment was evaluated at
      different solid contents of sediments in a bench-scale reactor. Results showed
      that a temporal change of pH in the bioleaching process was effected by the
      buffering capacity of the sediment particulates. The variations of pH in this
      bioleaching process were calculated by a modified logistic model. It was observed
      that solubilization of heavy metals from sediments is highly pH-dependent. In
      addition, a non-linear equation for metal solubilization relating pH value in the
      bioleaching process was established. This allows an easier and faster estimate of
      metal solubilization by measuring pH in the bioleaching process.

PMID- 11513397
TI  - Enzymatic treatment of sanitary landfill leachate.
AB  - The objective of this investigation was to study the effectiveness of applying
      enzymes (bioaugmentation) for enhancement of biological treatability of leachates
      generated in a typical municipal solid waste sanitary landfill. The basic purpose
      of enzyme use is to enforce the biodecomposition of organic constituents, as well
      as to reduce nitrogen content. A laboratory-scale sequencing batch (bio)reactor
      (SBR) was used for the examination of enzymatic application. The effect of
      different operation strategies on the efficiency of this biological treatment
      process was studied to optimize performance, especially for the removal of
      nitrogen compounds and of biodegradable organic matter. It was found that the
      enzymatic process was able to remove organic matter effectively (expressed as
      BOD5 and COD) and nitrogen content, color and turbidity.

PMID- 11513398
TI  - Activation of H2O2 by Amberlyst-15 resin supported with copper(II)-complexes
      towards oxidation of crystal violet.
AB  - Copper(II) amine complexes supported on Amberlyst-15 cation resin were prepared
      and characterized by SEM, EDX and FTIR measurements. The kinetics of the
      heterogeneous oxidation of an organic dye, crystal violet, with H2O2 catalyzed by
      the supported catalysts was investigated in aqueous solution. The rate of
      reaction increases with increasing stability of the copper(II) amine complexes.
      The oxidation rate attained a first-order in the catalyst and the dye only at
      lower concentrations and second order in H2O2. A very fast formation of a peroxo
      dye intermediate resulting from the interaction of H2O2 with the dye even in the
      presence of the catalyst was observed.

PMID- 11513399
TI  - Sorption of organic contaminants in a fractured chalk formation.
AB  - Sorption capability of bedrock components from a fractured chalk province was
      evaluated using ametryn, phenanthrene, m-xylene, 2,4,6-tribromophenol, and 1,2
      dichloroethane. Sorption isotherms for the four aromatic compounds were nonlinear
      on gray (unoxidized) chalk. Over the studied solution ranges, the distribution
      coefficient decreased by factor of 3 for phenanthrene and m-xylene, a factor 4
      for ametryn, and by an order of magnitude for 2,4,6-tribromophenol. In contrast,
      1,2-dichloroethane displayed a linear isotherm. The importance of polar
      interactions for ametryn sorption was evaluated by normalizing sorption to an
      "inert" solvent, n-hexane. n-Hexane-normalized sorption of ametryn was much
      greater than that of phenanthrene, presumably due to ametryn participation in
      hydrogen bonding interactions. In sharp contrast to sorption to gray chalk,
      sorption to white (oxidized) chalk is 100- to 1000-fold lower at any given
      solution concentration. The much greater sorption on gray chalk cannot be
      explained by specific surface area, clay content, or organic matter content;
      thus, the nature of the organic matter is considered to control sorption in the
      chalk samples. Gray chalk sorption capacity estimates for ametryn and 2,4,6
      tribromophenol are similar, which, together with evidence of competition for
      sorption sites, suggests that the limited capacity sorption domain for both
      compounds is similar.

PMID- 11513400
TI  - Bioremediation of coal tar PAH in soils using biodiesel.
AB  - The addition of biodiesel together with nitrate and phosphate to soil containing
      coal tar, in laboratory and field experiments, resulted in degradation of coal
      tar polycyclic aromatic hydrocarbons (PAH) that was not apparent when the
      nutrients alone were added. The addition of motor diesel fuel instead of
      biodiesel was also tested. Over the 55 days of the field and laboratory
      experiments, the biodiesel resulted in an increased degradation of naphthalene in
      the coal tar by 52% and 85%, respectively, and motor diesel resulted in increased
      depletions of 85% and 96%, respectively. Other PAH containing up to four rings
      were depleted to lesser extents. The increases in PAH biodegradation by the
      diesel treatments were ascribed to tar solubilisation and dispersion thereby
      increasing the PAH bioavailability. The ready biodegradability and low
      phytotoxicity of biodiesel suggest that it may be suitable as a novel treatment
      for the bioremediation of coal tar contaminated soils.

PMID- 11513401
TI  - Cosolvent effects of alcohols on the Henry's law constant and aqueous solubility
      of tetrachloroethylene (PCE).
AB  - The effects of selected cosolvents ethyl alcohol (EtOH), isopropyl alcohol (IPA),
      and tertbutyl alcohol (TBA) on the Henry's law constant (H) of
      tetrachloroethylene (PCE) in aqueous solutions were investigated using the static
      headspace method. Alcohols in solution at a concentration around 20% and above
      acted as cosolvents increasing the aqueous solubility of PCE, which resulted in
      lower H values for PCE as compared to the value of H in deionized water. TBA, the
      most hydrophobic of the three alcohols, exhibited the strongest cosolvent
      effects, while EtOH had the weakest effects. A ln-linear relationship was
      observed between H and the volumetric fraction of alcohol added. Investigation of
      the solubilization of PCE in alcohol solutions confirmed the cosolvent trend
      observed for the three alcohols. A ln-ln relationship was observed between H and
      the enhanced solubility of PCE at a particular alcohol concentration. It was also
      observed that the value of H is a function of the enhanced solubility regardless
      of the type of cosolvent used. The results from this research further define the
      behavior of PCE in alcohol flooding solutions used in the remediation of PCE
      contaminated media.

PMID- 11513402
TI  - Photo-oxidation of biodegraded crude oil and toxicity of the photo-oxidized
      products.
AB  - We investigated the physicochemical changes resulting from irradiation by
      sunlight of biodegraded crude oil. An Arabian light crude oil sample was first
      subjected to microbial degradation. n-Alkanes and aromatic compounds such as
      naphthalenes, fluorenes, dibenzothiophenes and phenanthrenes possessing short,
      alkyl side chain(s) were almost completely degraded, while the contents of the
      saturated and aromatic fractions were reduced by 70% and 40%, respectively. This
      biodegraded oil was then suspended in seawater and exposed to sunlight
      irradiation for several weeks. The most remarkable change caused by the
      irradiation was a substantial decline in the aromatic fraction with a concomitant
      increase in the resin and asphaltene fractions. A 13C-nuclear magnetic resonance
      (NMR) spectroscopic analysis showed that the aromaticity of the biodegraded oil
      was significantly lower in the irradiated sample. A field desorption-mass
      spectrometric (FD-MS) analysis showed that sunlight irradiation reduced the
      average molecular weight of the oil components and formed oxygenated compounds.
      Consistent with this observation is that the oxygen content in the oil increased
      as the irradiation was prolonged. The bioavailability of the biodegraded oil was
      increased by the photo-oxidation: the growth of seawater microbes was minimal
      when the non-irradiated biodegraded oil was used as the source of carbon and
      energy; however, growth was significant when irradiated biodegraded oil was used.
      The concentration of dissolved organic carbon (DOC) increased linearly during the
      sunlight irradiation of the biodegraded oil, and this increase was matched by an
      increase in ultraviolet-absorptive materials in the seawater. The photochemically
      formed, water-soluble fraction (WSF) showed acute toxicity against the halophilic
      crustacean, Artemia.

PMID- 11513403
TI  - The organic precursors affecting the formation of disinfection by-products with
      chlorine dioxide.
AB  - The object of this research was to study the formation of disinfection by
      products by using chlorine dioxide (ClO2) as a disinfectant reacting with
      different properties of organic substance in natural aquatic environment. The
      adsorbent resin (XAD-4, XAD-7) was used to divide the organic matters in raw
      water into three groups. The influence of the function groups on structure,
      reaction tendency, and formation of disinfection by-products generated by the
      reaction of these organic substances with chlorine dioxide was explored. The
      experimental results show that the three different organic groups formed using
      adsorbent resin were hydrophobic substance, hydrophilic acid, and non-acid
      hydrophilics in proportions of 43%, 41%, and 16%, respectively. Within the raw
      water in our study, the hydrophilic substance had a higher distribution
      proportion than that described in general articles and journals, which indicates
      that this water was contaminated with pollution from human beings. The
      exploration of the reactivity of the three different organic substances with
      chlorine dioxide shows that the unit consumption of disinfection agent per unit
      organic matters (represented by ClO2/DOC) is in the following sequence
      hydrophobic substance > hydrophilic substance > non-acid hydrophilics. It
      indicated that larger molecular organic precursors had larger consumption of
      disinfectant. We also discovered that after the reaction of the three different
      organic substances with chlorine dioxide, the largest amount of disinfection by
      products were generated by the non-acid hydrophilics.

PMID- 11513404
TI  - Photocatalytic degradation of dyes on a magnetically separated photocatalyst
      under visible and UV irradiation.
AB  - A novel kind of magnetically separable photocatalyst of TiO2/SiO2/gamma-Fe2O3
      (TSF) is prepared. Scanning tunnel microscope (STM) and X-ray diffractometer
      (XRD) were used to characterize the structure of the photocatalyst. In the TSF
      photocatalyst, a TiO2 shell is for photocatalysis, a gamma-Fe2O3 core as a
      carrier is for separation by the magnetic field and a SiO2 membrane between the
      TiO2 shell and the gamma-Fe2O3 core is used to weaken the adverse influence of
      gamma-Fe2O3 on the photocatalysis of TiO2. Three kinds of dyes, Fluoresein,
      Orange II and Red acid G, were used to examine the photocatalytic activity of
      TSF. Due to strong UV adsorption of the gamma-Fe2O3, the photocatalytic activity
      of TSF was lower than that of the pure TiO2. Deducting the light absorption of
      the gamma-Fe2O3 particles, the photocatalytic activity of TSF was found to be
      higher than that of the P25 under UV irradiation. On the other hand, the
      photocatalytic activity of TSF under visible irradiation was much lower than that
      of the P25 TiO2 even deducting the visible light absorption of the gamma-Fe2O3
      particles. Differences in the photocatalytic mechanisms under UV and visible
      irradiation lead to the differences in the photodegradation characteristics of
      dyes on TSF. The recycled TSF exhibited a good repeatability of photocatalytic
      activity.

PMID- 11513405
TI  - Azo dye decolourisation by anaerobic granular sludge.
AB  - The decolourisation of 20 selected azo dyes by granular sludge from an upward
      flow anaerobic sludge bed (UASB) reactor was assayed. Complete reduction was
      found for all azo dyes tested, generally yielding colourless products. The
      reactions followed first-order kinetics and reaction rates varied greatly between
      dyes: half-life times ranged from 1 to about 100 h. The slowest reaction rates
      were found for reactive dyes with a triazine reactive group. There was no
      correlation between a dye's half-life time and its molecular weight, indicating
      that cell penetration was probably not an important factor. Since granular sludge
      contains sulphide, eight dyes were also monitored for direct chemical
      decolourisation by sulphide. All these dyes were reduced chemically albeit at
      slower rates than in the presence of sludge at comparable sulphide levels.
      Increasing sulphide concentrations, even when present in huge excess, stimulated
      the azo reduction rate. The results indicate that granular sludge can decolourise
      a broad spectrum of azo dye structures due to non-specific extracellular
      reactions. Reducing agents (e.g., sulphide) in sludge play an important role. The
      presence of anaerobic biomass is probably beneficial for maintaining the pools of
      these reduced compounds.

PMID- 11513406
TI  - Removal of metal ions and humic acid from water by iron-coated filter media.
AB  - Iron oxide is an excellent, regenerable adsorbent, and often controls free metals
      through adsorption reaction. The utilization of heating process for coating iron
      oxide on sand surface allowed the media to be used in a packed column. Iron
      coated sand was investigated for adsorbing metal ions and natural organic matter
      from water by batch and column experiments. Chemical analysis (energy dispersive
      analysis of X-ray, EDAX) was used for characterizing the copper and lead
      adsorption sites on iron-coated sand. From the batch experiment results, the
      copper and lead ions could be removed simultaneously by the iron-coated sand in
      the competition adsorption system. The interaction between copper, lead ions and
      iron oxide on sand surface was primarily the chemical bonds. The maximum
      adsorption capacities of iron-coated sand for copper and lead were 0.259 mg Cu/g
      sand and 1.211 mg Pb/g-sand, respectively. The presence of humic acid led to
      increase the adsorption of copper and lead. Results from column experiments
      indicated that the copper ions, lead ions and humic acid could be removed
      completely before the breakpoint. Consequently, the iron-coated sand may be
      applied for the adsorption/filtration of metal ions and natural organic matters
      from water.

PMID- 11513407
TI  - Effect of fly ash characteristics on the removal of Cu(II) from aqueous solution.
AB  - Fly ash is a particulate substance containing metal oxides, carbon and other
      microelements. In this study, fly ashes with different quantities of carbon and
      minerals prepared by a thermal process in the laboratory were used as adsorbents
      to investigate the contribution of precipitation and adsorption to the removal of
      aqueous Cu(II). Experimental results showed that the specific surface area of fly
      ash increased linearly with the quantity of carbon. The specific surface areas of
      the carbon and mineral fraction were 60 m2/g and 0.68 m2/g, respectively. The
      specific adsorption capacities of carbon ranged from 2.2 to 2.8 mg Cu/g carbon,
      while those for mineral were only about 0.63 to approximately 0.81 mg Cu/g
      mineral. Consequently, the carbon fraction in fly ash was important in the
      removal of Cu(II) at pH 5. However, Cu(II) removal owing to precipitation
      increases with a decreasing carbon fraction and the contribution of copper
      precipitation was estimated to be approximately 23% to approximately 82% of total
      removal, depending on the carbon fraction of fly ash.

PMID- 11513408
TI  - Hydroxyl radical scavenging role of chloride and bicarbonate ions in the H2O2/UV
      process.
AB  - Simultaneous effect of inorganic anions, such as chloride and bicarbonate ions,
      on the scavenging of hydroxyl radicals (HO*) in the H2O2/UV process is the focus
      of this paper. The model compound of n-chlorobutane (BuCl) was used as the probe
      of HO*. By changing the pH conditions (2-9) and the concentrations of NaCl (0.25
      2500 mM) and NaHCO3 (25 mM), the variation of HO* concentrations and the rate of
      H2O2 decomposition were compared. In general, the BuCl and H2O2 follow closely
      the first-order reaction within the first 10 and 40 min, respectively. In the
      presence of chloride alone at the pH range of 2-6, the HO* concentration in the
      reaction mixture increases with the increase of pH, and the HO* concentration at
      pH = 6 is 100 times of that at pH = 2. Including bicarbonate species in the
      solution, the peak HO* concentration was found at a certain pH, which shifts from
      4, 5, to 5-7, as the molar ratios of chloride/bicarbonate species increase from 1
      to 100. In addition, without bicarbonate species HO* concentration decreases
      significantly with increasing chloride concentration but remained rather
      unchanged beyond 1250 mM. In contrast, the HO* scavenging in the presence of
      bicarbonate species became relatively significant only when the chloride
      concentration reached beyond 250 mM. Throughout all experiments of different
      water quality conditions, the H2O2 decomposition rate remains rather unchanged.

PMID- 11513409
TI  - Kinetics of thermophilic anaerobes in fixed-bed reactors.
AB  - The main objective of this study is to estimate growth kinetic constants and the
      concentration of "active" attached biomass in two anaerobic thermophilic reactors
      which contain different initial sizes of immobilized anaerobic mixed cultures and
      decompose distillery wastewater. This paper studies the substrate decomposition
      in two lab-scale fixed-bed reactors operating at batch conditions with corrugated
      tubes as support media. It can be demonstrated that high micro-organisms
      substrate ratios favor the degradation activity of the different anaerobic
      cultures, allowing the stable operation without lag-phases and giving better
      quality in effluent. The kinetic parameters obtained--maximum specific growth
      rates (mu(max)), non-biodegradable substrate (S(NB)) and "active or viable
      biomass" concentrations (X(V0))--were obtained by applying the Romero kinetic
      model [L.I. Romero, 1991. Desarrollo de un modelo matematico general para los
      procesos fermentativos, Cinetica de la degradacion anaerobia, Ph.D. Thesis,
      University of Cadiz (Spain), Serv. Pub. Univ. Cadiz], with COD as substrate and
      methane (CH4) as the main product of the anaerobic process. This method is
      suitable to calculate and to differentiate the main kinetic parameters of both
      the total anaerobic mixed culture and the methanogenic population. Comparison of
      experimental measured concentration of volatile attached solids (VS(att)) in both
      reactors with the estimated "active" biomass concentrations obtained by applying
      Romero kinetic model [L.I. Romero, 1991. Desarrollo de un modelo matematico
      general para los procesos fermentativos, Cinetica de la degradacion anaerobia,
      Ph.D. Thesis, University of Cadiz (Spain), Serv. Pub. Univ. Cadiz] shows that a
      large amount of inert matter is present in the fixed-bed reactor.

PMID- 11513410
TI  - Relationship between release of nitric oxide and CO2 and their dependence on
      oxidation reduction potential in wastewater treatment.
AB  - Nitric oxide (NO) is an intermediate of denitrification process and can be
      produced by denitrifiers, nitrifiers and other bacteria. In our experiments we
      measured the dynamic flow of NO depending on oxidation reduction potential (ORP).
      Different ORP-ranges were related to various carbon loading stages in the
      wastewater treatment pilot plant. Nitrification and denitrification were achieved
      by a sequence of aeration and non-aeration periods. Our measurements show that
      different carbon loading conditions (low feed, balanced and overloaded
      conditions) did not change the range of the mixing ratio of NO emissions when the
      aeration conditions like air-flow and temperature were kept constant. Minimum and
      maximum NO mixing ratios were 34.7 and 91.8 ppbv; 52.3 and 91.3 ppbv; 57.6 and
      109 ppbv for low feed, balanced and overloaded conditions, respectively. The
      curve of the NO graph relied on nitrification/denitrification dynamics. The
      dependence of NO release on different ORP and CO2-release during the various
      conditions are shown. Longer aeration times resulted in an increased release of
      gaseous NO. The net-release of NO g(-1) nitrogen removed was between 0.014% and
      0.028%. The NO fluxes to the air were observed between 8.3 and 14.9 mg m(-2) d(
      1) NO. The major release occurred during high aeration periods whereas the
      concentration of dissolved [NOaq] in the wastewater was less than 0.05% of the
      gaseous release due to very low solubility of the NO.

PMID- 11513411
TI  - Simultaneous recovery of copper and degradation of 2,4-dichlorophenoxyacetic acid
      in aqueous systems by a combination of electrolytic and photolytic processes.
AB  - In mixed industrial effluent the presence of metal ions can retard the
      destruction of organic contaminants and the efficiency of recovery of the metal
      is reduced by the presence of the organic species. Results are presented for
      copper-2,4-dichlorophenoxyacetic acid (2,4-D) system in which both effects occur.
      An electrochemical cell alone can be used to recover copper in the pH range 1.5
      4.5 but it is not capable of achieving complete disappearance of 2,4-D by anodic
      oxidation. A photolytic cell alone can achieve the destruction of 2,4-D at pH 3.5
      but leaves copper in solution. A combined photolytic-electrochemical system using
      an activated carbon concentrator cathode achieves the rapid simultaneous
      destruction of 2,4-D and recovery of copper. Results are presented for the
      recovery of more than 90% copper from, and >99.9%, destruction of the
      organochlorine compound 2,4-D in, a solution containing 100 mg dm(-3) copper and
      50 mg dm(-3) 2.4-D. The photolytic degradation of 2,4-D depends on the intensity
      of the UV-probe. Only 19% degradation is achieved after 8 h with the 150 W UV
      probe but the corresponding value with the 400 W UV-probe is 100%. In the case of
      150 W UV-probe the degradation of 2,4-D proceeds through the formation of 2,4
      dichlorophenol and phenol. The concentration of these intermediates are very low
      in the case of 400 W UV-probe because the speed of the degradation of 2,4-D is
      very fast. The addition of TiO2 (1 g dm(-3)), as a semiconductor material, and
      H202 (1.5 g dm(-3)) as an oxidant, increases the photolytic degradation of 2,4-D.

PMID- 11513412
TI  - Characteristics of organic precursors and their relationship with disinfection by
      products.
AB  - The molecular weight distribution and chemical composition of precursors and
      their relationship with disinfection by-products (DBPs) were investigated. Most
      of the organic matter responsible for the major DBP precursors in the Pan-Hsin
      water are small compounds with a molecular weight less than 1 kDa. The
      hydrophobic acids display the greatest ability to produce DBP. Therefore,
      effective removal of small molecules or hydrophobic acidic organics prior to
      disinfection process will significantly reduce the DBP concentration in the
      finished water. Although the coagulation process is effective in removing large
      organic precursors and the removal efficiencies of CHCl3 formation potential and
      organic carbon increase proportionally to the molecular weight of the precursors,
      the conventional treatment methods have limited efficiency in eliminating small
      precursors, which have high DBP formation potential.

PMID- 11513413
TI  - Lipophilic extractives in process waters during manufacturing of totally chlorine
      free kraft pulp from eucalypt wood.
AB  - The chemical composition of lipophilic extractives from process waters throughout
      a totally chlorine free (TCF) bleaching sequence after kraft pulping of eucalypt
      wood has been studied. These compounds are among the most problematic wood
      constituents for both TCF and zero liquid effluent (ZLE) processes, since they
      tend to accumulate in circuits resulting in the formation of the so-called pitch
      deposits causing serious problems in the pulp and paper industry. Pitch deposits
      collected at different parts of the pulp mill were also characterized and their
      composition compared with that of lipophilic compounds in process waters and
      Eucalyptus globulus wood. The identification of these compounds from process
      waters, wood and pitch deposits was performed by gas chromatography and gas
      chromatography-mass spectrometry using short- and medium-length high temperature
      capillary columns. Sterols, sterol esters, steroid ketones and steroid
      hydrocarbons were the main compounds identified. These chemical species arise
      from eucalypt wood extractives that survive the pulping and are released from
      pulp into the process waters during the bleaching process. Finally, they can
      deposit in pulp and on different parts of the mill or remain suspended in process
      waters being discharged in effluents.

PMID- 11513414
TI  - Combustion of gasolines in premixed laminar flames European certified and
      California phase 2 reformulated gasoline.
AB  - Two gasoline qualities, European unleaded certified gasoline (EUCG) and
      California phase 2 reformulated gasoline (P2 RFG), were analysed. EUCG contained
      about twice the amount of alkyl benzenes compared to P2 RFG and a large amount of
      cyclohexane. As a balance, P2 RFG contained higher amounts of isooctane and MTBE.
      The gasolines were burned in a premixed laminar flame burner at 1 atm and at
      about stoichiometric fuel/air ratio. The species profiles were measured using on
      line GC/MS. About 40 compounds were be detected in the gasoline flames. The EUCG
      resulted in formation of more reactive and toxic compounds. The combustion
      profiles of the fuel components showed a similar slope, which suggests that the
      fuel components burn quite independently of each other. Ethene and propene were
      the dominating species produced from the two gasolines. Commonly, substantial
      amounts of higher alkenes were found. Combustion of P2 RFG produced higher
      amounts of isobutene, propene, propyne, propadiene and methanol compared to
      combustion of EUCG. The high amount of isobutene is reasonably a result of high
      concentration of isooctane and MTBE in the fuel. The high amount of methanol
      formed is probably due to the MTBE present in the gasoline. EUCG produced
      significantly higher amounts of 1,3-butadiene, which quite likely is formed from
      the cyclohexane in the fuel. The benzene profiles from both gasolines shows an
      almost constant level up to 800 microm from the burner surface; this is probably
      due to formation of benzene from alkyl benzenes.

PMID- 11513415
TI  - Comparison of models for describing measured VOC emissions from wood-based panels
      under dynamic chamber test condition.
AB  - Measured emission factors are the experimental data used to represent emission
      characteristics of volatile organic compounds (VOCs) from testing materials under
      dynamic chamber test conditions. A simple empirical model that describes the
      measured emission factors will be very useful for practical purposes. In this
      study, a power law model was compared with a widely used first-order exponential
      decay model in their ability to describe measured emission factors of wood-based
      panel materials. It was demonstrated that the power law model is a better choice
      than the first-order model for describing emission characteristics for short-term
      (less than 100 h) experimental data. The power law model was also more superior
      in predicting long-term (up to 900 h) emission factors.

PMID- 11513416
TI  - Studies on plant-mediated fate of the explosives RDX and HMX.
AB  - The fate of the explosives RDX and HMX on exposure to plants was investigated in
      'natural' aquatic systems of Myriophyllum aquaticum for 16 days, and in axenic
      hairy root cultures of Catharanthus roseus for > or = 9 weeks. Exposure levels
      were: HMX, 5 mg/l; and RDX, approximately 8 mg/l. Exposure outcomes observed
      include: HMX, no transformation by aquatic plants, and minimal biological
      activity by axenic roots; and RDX, removal by both plant systems. In the case of
      RDX exposure to axenic roots, since 14C-RDX was included, removal was confirmed
      by the accumulation of 14C-label in the biomass. The intracellular 14C-label in
      these RDX studies was detected in two forms: intact RDX and bound unknown(s).

PMID- 11513418
TI  - Estimation of biodegradation parameters of phenolic compounds on activated sludge
      by respirometry.
AB  - The bio-oxidation of phenol, catechol, resorcinol, m-cresol and 5
      methylresorcinol on activated sludge was investigated by oxygen uptake
      measurements. In addition, the degradation of acetate with the same microbial
      population was studied. The substrate-dependent oxygen uptake data were analysed
      on the basis of the Michaelis-Menten kinetics. The extant kinetic parameters, the
      maximum rates of oxygen consumption and half-saturation constants for the
      processes with different substrates were determined. The simple respirometric
      approach also made it possible to determine the short-term oxygen demands of the
      substrates which formed 23-38% of the theoretical oxygen demand of the studied
      compounds.

PMID- 11513417
TI  - Fate of pyrene in contaminated soil amended with alternate electron acceptors.
AB  - Creosote-contaminated soil samples from the Libby Ground Water Contamination
      Superfund Site in Libby, MT, were amended with the potential alternate electron
      acceptors (AEA) nitrate (KNO3), manganese oxide (MnO2), and amorphous iron
      oxyhydroxide (FeOOH) and incubated at low oxygen tensions (0-6% O2). The fate of
      14C-pyrene was evaluated with respect to the different soil amendments. The fate
      of 14C from the radiolabeled pyrene with regard to mineralization and bound
      residue formation within soil humic fractions was not significantly different
      from controls for the iron and manganese amended soils. Nitrate amendments
      appeared to stimulate 14C-pyrene mineralization at a level of 170 mg NO3-N kg(
      1), and inhibit mineralization at 340 mg NO3-N kg(-1). The stimulatory effect did
      not appear to be the result of nitrate serving as an electron acceptor. Although
      AEA amendments did not significantly affect the rate or extent of 14C-pyrene
      mineralization, results of oxygen-deprived incubations (purged with N2) indicate
      that AEA may be utilized by the microbial community in the unsaturated
      contaminated soil system.

PMID- 11513419
TI  - Carbon isotope fractionation during abiotic reductive dehalogenation of
      trichloroethene (TCE).
AB  - Dehalogenation of trichloroethene (TCE) in the aqueous phase, either on palladium
      catalysts with hydrogen as the reductant or on metallic iron, was associated with
      strong changes in delta13C. In general, the delta13C of product phases were more
      negative than those of the parent compound and were enriched with time and
      fraction of TCE remaining. For dehalogenation with iron, the delta13C of TCE and
      products varied from -42/1000 to +5/1000. For the palladium experiments, the
      final product, ethane, reached the initial delta13C of TCE at completion of the
      dehalogenation reaction. During dehalogenation, the carbon isotope fractionation
      between TCE and product phases was not constant. The variation in delta13C of TCE
      and products offers a new monitoring tool that operates independently of the
      initial concentration of pollutants for abiotic degradation processes of TCE in
      the subsurface, and may be useful for evaluation of remediation efficiency.

PMID- 11513420
TI  - Interactions between organic flocculant PAN-DCD and dyes.
AB  - Organic flocculant polyacrylonitrile-dicyandiamide (PAN-DCD) was characterized by
      IR, 1H NMR and 13C NMR spectra. Polar groups, such as triazine, carboxyl,
      amidine, carbonamide and non-polar groups, such as methylene were identified in
      the macromolecular chain of PAN-DCD. The flocculant effectively decolorized the
      examined dyes in their aqueous solutions under acid condition. By comparing the
      IR spectra of dyes with that of PAN-DCD and that of flocs formed, weak chemical
      interactions between amino in PAN-DCD side chain and sulfonic acid group in the
      dye molecules were observed through the formation of -NH3+ SO3(-)-, NH2+ SO3(-)-
      or/and =NH+ SO3(-)-. By using equilibrium dialysis technique, the hydrophobic
      interactions between PAN-DCD and the dyes in the binding process were also
      observed from the experimental results. The binding extent of PAN-DCD to dye KN-R
      was greater than that of MO. The addition of urea into the binding system of KN-R
      by PAN-DCD reduced the first binding constant K from 12.2 x 10(5) (without urea)
      to 3.48 x 10(5) (with urea).

PMID- 11513421
TI  - Photosonochemical degradation of trichloroacetic acid in aqueous solution.
AB  - The degradation of trichloroacetic acid (TCA) was studied with ultraviolet (UV)
      photolysis, ultrasound (US) sonolysis and their combination. It was found that
      the degradation in the combined processes was more significant than in the UV
      photolysis or sonolysis alone. The effects of pH and dissolved gases on the rate
      of photosonochemical degradation of TCA were investigated and the degradation
      kinetics, mechanism and possible degradation products were discussed in detail.

PMID- 11513422
TI  - Investigation of the behaviour of haloketones in water samples.
AB  - The behaviour of the haloketones (HKs) 1,1-Dichloropropanone (1,1-DCP), 1,1,1
      Trichloropropanone (1,1,1-TCP) and 1,3-Dichloropropanone (1,3-DCP) in ultrapure
      water solutions and in fortified drinking water samples was investigated. Their
      concentrations were determined at regular time intervals by the use of a gas
      chromatography-electron capture detector (GC-ECD) method. Two different
      temperatures were studied. The results have shown that HKs decompose both in
      ultrapure water solutions and in drinking water samples. The decomposition rates
      are higher in the drinking water samples, especially at higher temperature. 1,1,1
      TCP is the compound which decomposes fastest followed by 1,3-DCP and 1,1-DCP.
      Chloroform was formed both in the ultrapure water solutions and in the drinking
      water samples, probably due to the decomposition of 1,1,1-TCP. In the drinking
      water samples, formation of chloral hydrate was also observed.

PMID- 11513423
TI  - Role of cupric ions in the H2O2/UV oxidation of humic acids.
AB  - The purpose of this study is to reveal the role of cupric ions as a natural water
      contaminant in the H2O2/UV oxidation of humic acids. Humic acids are naturally
      occurring organic matter and exhibit a strong tendency of complexation with some
      transition metal ions. Chlorination of humic acids causes potential health
      hazards due to formation of trihalomethane (THM). The removal of THM precursors
      has become an issue of public concern. The H2O2/UV process is capable of
      mineralizing humic acids due to formation of a strong oxidant, hydroxyl radicals,
      in reaction solution. Experiments were conducted in a re-circulated photoreactor.
      Different cupric concentrations (0-3.8 mg/l) and different pH values (4-9) were
      controlled to determine their effects on the degradation of humic acids, UV light
      absorbance at 254 nm, and H2O2. The presence of cupric ions inhibits humic
      mineralization and decreases the rate of destruction of humic acids which absorb
      UV light at 254 nm. On the other hand, the higher the cupric concentration, the
      lower the H2O2 decomposition rate. In the studied pH range, the minimum of total
      organic carbon (TOC) removal occurs at pH = 6 in the presence of 2.6 mg/l of
      cupric ions; both acidification (pH = 4) and alkaline condition (pH = 9) lead to
      a better removal of TOC. It is inferred from this study that the cupric-complexed
      form of humic acids is more refractory than the non-complexed one.

PMID- 11513424
TI  - Simulation of atmospheric PAH emissions from diesel engines.
AB  - Simulation of atmospheric PAH emissions in a typical European passenger car
      diesel engine at steady conditions or under a certification cycle is made using
      in-house software. It is based on neural fitting of experimental data from eight
      different fuels tested under five operating steady conditions (reproducing modes
      of the European transient urban/extraurban certification cycle). The software
      allows the determination of PAH emissions as a function of the fuel composition
      parameters (aromatic content, cetane index, gross heat power, nitrogen and
      sulphur content) and operation conditions (torque and engine speed). The
      mathematical model reproduces experimental data with a maximum error of 20%. This
      tool is very useful, since changes in parameters can be made without experimental
      cost and the trend in modifications in PAH emissions is immediately obvious.

PMID- 11513425
TI  - Laboratory column studies for evaluating a barrier system for providing oxygen
      and substrate for TCE biodegradation.
AB  - The industrial solvent trichloroethylene (TCE) is among the most ubiquitous
      chlorinated compounds found in groundwater contamination. The objective of this
      study was to develop a biobarrier system containing oxygen-organic releasing
      material to enhance the aerobic cometabolism of TCE in situ. The oxygen-organic
      material, which contains calcium peroxide and peat, is able to release oxygen and
      primary substrates continuously upon contact with water. Batch experiments were
      conducted to design and identify the components of the oxygen-organic releasing
      material, and evaluate the oxygen and organic substrate (presented as COD
      equivalent) release from the designed oxygen-organic material. The observed
      oxygen and chemical oxygen demand (COD) release rates were approximately 0.0246
      and 0.052 mg/d/g of material, respectively. A laboratory-scale column experiment
      was then conducted to evaluate the feasibility of this proposed system for the
      bioremediation of TCE-contaminated groundwater. This system was performed using a
      series of continuous-flow glass columns including a soil column, an oxygen
      organic material column, followed by two consecutive soil columns. Aerobic
      acclimated sludges were inoculated in all three soil columns to provide microbial
      consortia for TCE biodegradation. Simulated TCE-contaminated groundwater with a
      flow rate of 0.25 l/day was pumped into this system. Effluent samples from each
      column were analyzed for TCE and other indicating parameters (e.g., pH, dissolved
      oxygen). Results show that the decreases in TCE concentrations were observed over
      a 4-month operating period. Up to 99% of TCE removal efficiency was obtained in
      this passive system. Results indicate that the continuously released oxygen and
      organic substrates from the oxygen-organic materials enhanced TCE
      biotransformation. Thus, the biobarrier treatment scheme has the potential to be
      developed into an environmentally and economically acceptable remediation
      technology.

PMID- 11513426
TI  - Modeling the quantum yields of herbicide 2,4-D decay in UV/H2O2 process.
AB  - The photodecay of herbicide 2,4-D in a hydrogen peroxide-aided photolysis process
      was studied and modeled. The decay rate of 2,4-D was known to be low in the
      natural environment, but rate improvement was achieved in an H2O2/UV system. The
      2,4-D decay quantum yields under ultraviolet (UV) light at 253.7 nm increased
      from 4.86 x 10(-6) to 1.30 x 10(-4) as the ratio of [H2O2]/[2,4-D] increased from
      0.05 to 12.5. Apparently, in the presence of UV light, the decay rate of 2,4-D
      could be greatly improved as the concentration of hydrogen peroxide increased.
      However, the efficiency of 2,4-D photodecay was retarded if the concentration of
      H2O2 was overdosed, because the excess hydrogen peroxide consumes the hydroxyl
      radicals (HO*) in the solution, resulting in a much weaker oxidant HO2*. The
      decay of 2,4-D was also pH dependent. A ranking of acid (highest), base (middle)
      and neutral (lowest) was observed owing to the property change of reactants and
      the shifting of dominant mechanisms among photolysis, photohydrolysis and
      chemical oxidation. Two mathematical models were proposed to predict the quantum
      yield for various [H2O2]/[2,4-D] ratios and initial pH levels, in which very good
      correlation was found for the ranges of regular application.

PMID- 11513427
TI  - The rate improvement and modeling of trichloroethene photodegradation by acetone
      sensitizer in surfactant solution.
AB  - The photodecay of trichloroethene (TCE) in surfactant solution by the help of
      photosensitizer (acetone, ACE) was investigated and modeled. Apart from the
      direct photodegradation, photosensitization is presumed to be one of the major
      mechanisms contributing to overall decay. Quantum yields of TCE photodecay in
      solution with surfactant Brij 35 and optimal ACE dosage are about 25 times higher
      than in Brij 35 alone. However, with an excess ACE dosage, ACE will act as a
      light barrier and attenuate the light intensity available for TCE
      photodegradation. TCE photodegradation follows a two-stage kinetics, in which a
      lag phase is followed by a fast decay. Mathematical models were developed for the
      prediction of the two-stage photodegradation, in which the remaining fraction of
      TCE (C/C0) in the system becomes predictable.

PMID- 11513428
TI  - Attempt to adsorb N-nitrosamines in solution by use of zeolites.
AB  - The strong adsorption of zeolite for N-nitrosamines in solution was first
      revealed by use of adsorption, and temperature programmed surface reaction (TPSR)
      techniques. N-nitrosodimethylamine (NDMA) and N-nitrosopyrrolidine (NPYR) as well
      as N-nitrosohexamethyleneimine (NHMI) can be adsorbed on zeolite Y, ZSM-5 and A
      in the solution of methylene chloride or water, which will be helpful for removal
      of the N-nitrosamines pollution in environmental protection. The equilibrium data
      were fitted to Freundlich-type isotherms, but the adsorption capacity of zeolites
      mainly depended on their pore size, surface area and acid-basic properties.
      Molecular size of adsorbate and solute-solvent interaction also strongly affected
      the adsorption of N-nitrosamines on zeolite in solution. The extraordinary
      adsorption properties of NaA zeolite for N-nitrosamines in aqueous solution is
      first reported and discussed.

PMID- 11513429
TI  - Decolorization of synthetic dyes by the Fenton reagent and the Cu/pyridine/H2O2
      system.
AB  - Representative azo, triphenylmethane, heterocyclic and polymeric synthetic dyes
      have been decolorized by two biological non-ezymatic systems,
      copper/pyridine/H2O2 and the Fenton reagent. With the former system, intensive
      decolorization measured after 1 h was obtained with phenol red (89%), tropaeolin
      00 (58%), Evans blue (95%), eosin yellowish (84%), and Poly B-411 (92%). The rate
      of decolorization was not affected by pH in the range of 3-9 and increased with
      increasing temperature. The use of the radical scavengers thiourea and superoxide
      dismutase showed that hydroxyl radicals rather than superoxide anions are
      involved in the reaction. Omission of pyridine led to a substantial decrease in
      the extent of decolorization (20-50% decolorization). The use of organic peroxide
      instead of H2O2 resulted in slightly slower decolorization, similar values of
      decolorization being obtained only after a 2-h incubation. Decolorization of the
      dyes by the Fenton reagent was also very effective but slower than that obtained
      with the first system. Except for phenol red and eosin yellowish, (decolorization
      8% and 52%, respectively) the dyes were decolorized up to 99% after 1-day
      incubation.

PMID- 11513430
TI  - Enhanced naphthalene solubility in the presence of sodium dodecyl sulfate: effect
      of critical micelle concentration.
AB  - Surfactants can increase the solubility of non-polar compounds, and have been
      applied in areas such as soil washing and treatment of non-aqueous phase liquids
      (NAPLs). This investigation explored the feasibility of removing vapor phase
      polycyclic aromatic hydrocarbon (PAH) from gases using an anionic surfactant. The
      solubility of vapor phase naphthalene was measured herein using gas chromatograph
      (GC) with a photon ionization detector (PID). The measurement results indicated
      that surfactant molecules were not favorable to micelle formation when
      temperatures increased from 25 degrees C to 50 degrees C. Regardless of whether
      solutions were quiescent or agitated, equilibrium naphthalene apparent solubility
      increased linearly with surfactant concentrations exceeding critical micelle
      concentration (CMC). The pH effects on naphthalene apparent solubility were
      small. Agitation increased naphthalene apparent solubility and lumped mass
      transfer coefficients. Furthermore, lumped mass transfer coefficients decreased
      with increasing surfactant concentration owing to increase in interfacial
      resistance and viscosity and decreased spherical micelle diffusion coefficients.
      Finally, the net absorption rate increased because the solubilization effects of
      micelles exceeded the reduction effects of mass transfer coefficient above the
      CMC. The enhanced naphthalene apparent solubility from the addition of surfactant
      can be expressed by an enrichment factor (EF). The EF value of naphthalene for
      the surfactant solution at 0.1 M with agitation at 270 rpm relative to quiescent
      water could reach 18.6. This work confirms that anionic surfactant can improve
      the removal efficiency of hydrophobic organic compound (HOC) from the gas phase.

PMID- 11513431
TI  - Identification and quantification of chlorinated bisphenol A in wastewater from
      wastepaper recycling plants.
AB  - Chlorinated derivatives of bisphenol A were detected in the final effluents of
      eight paper manufacturing plants in Shizuoka, Japan, where thermal paper and/or
      other printed paper is used as the raw material. Their amounts were determined by
      gas chromatography/mass spectrometry (GC/MS) after treatment with N, O
      bis(trimethylsilyl)trifluoroacetamide, and ranged from traces to 2.0 microg/l.
      They are likely produced by chlorination of bisphenol A, which was released into
      the effluents from the pulping process of wastepaper, during or after bleaching
      with chlorine.

PMID- 11513432
TI  - Distribution behavior of heavy metals investigated in a laboratory-scale
      incinerator.
AB  - The distribution behavior of Pb, Cd, Fe, Cu, Mo and Zn was determined in a
      laboratory-scale incinerator. Points of interest were the influence of the
      temperature and combustion atmosphere on the emission rates of those metals,
      orientating at frequent combustion conditions of accidental fires. The
      experiments were carried out at 600 degrees C and 800 degrees C in N2, air, N2 +
      HCl and air + HCl atmospheres. Furthermore, the influence of the matrix (quartz,
      polyethylene and cellulose powder) on the distribution behavior of the heavy
      metals was investigated as well. It was determined whether the distribution
      behavior of Cu, Pb and Cd were affected by the other heavy metals. In conclusion,
      it was found that in air and N2 atmosphere a temperature increase from 600
      degrees C to 800 degrees C and the addition of the matrix had no effect on the
      evaporation rates of the heavy metals, except for Cd. Addition of gaseous HCl led
      to increased evaporation of the heavy metals. The increase of the evaporation
      rates during the experiments with matrix was higher for Fe, remained the same for
      Pb, Cd, Zn, and lower for Mo and Cu compared to the experiments without matrix.

PMID- 11513433
TI  - Preparations of organobentonite using nonionic surfactants.
AB  - Due to hydrophilic environment at its surface, natural bentonite is an
      ineffective sorbent for nonpolar nonionic organic compounds in water even though
      it has high surface area. The surface properties of natural bentonite can be
      greatly modified by simple ion-exchange reactions with large organic cations
      (cationic surfactants) and this organobentonite is highly effective in removing
      nonionic organic compounds from water. Cationic surfactant derived
      organobentonites have been investigated extensively for a wide variety of
      environmental applications. In this study, the preparation of organobentonite
      using nonionic surfactants has been investigated for the first time. Results
      indicate that nonionic surfactants intercalates into the interlamellar space of
      bentonite and may demonstrate higher sorption capacity than cationic surfactant.
      It is possible to create large interlayer spacing and high organic carbon content
      organobentonite by use of nonionic surfactants with suitable balance between the
      hydrocarbon and ethylene oxide chain lengths. In addition, nonionic surfactant
      derived organobentonites are more chemically stable than cationic surfactant
      derived organobentonites.

PMID- 11513434
TI  - Loading estimates of lead, copper, cadmium, and zinc in urban runoff from
      specific sources.
AB  - Urban stormwater runoff is being recognized as a substantial source of pollutants
      to receiving waters. A number of investigators have found significant levels of
      metals in runoff from urban areas, especially in highway runoff. As an initiatory
      study, this work estimates lead, copper, cadmium, and zinc loadings from various
      sources in a developed area utilizing information available in the literature, in
      conjunction with controlled experimental and sampling investigations. Specific
      sources examined include building siding and roofs; automobile brakes, tires, and
      oil leakage; and wet and dry atmospheric deposition. Important sources identified
      are building siding for all four metals, vehicle brake emissions for copper and
      tire wear for zinc. Atmospheric deposition is an important source for cadmium,
      copper, and lead. Loadings and source distributions depend on building and
      automobile density assumptions and the type of materials present in the area
      examined. Identified important sources are targeted for future comprehensive
      mechanistic studies. Improved information on the metal release and distributions
      from the specific sources, along with detailed characterization of watershed
      areas will allow refinements in the predictions.

PMID- 11513435
TI  - Atrial size reduction as a predictor of the success of radiofrequency maze
      procedure for chronic atrial fibrillation in patients undergoing concomitant
      valvular surgery.
AB  - INTRODUCTION: Previous studies showed that the surgical maze procedure can
      restore sinus rhythm and atrial transport function in patients with chronic
      atrial fibrillation (AF). However, no previous studies discussed the association
      of atrial size reduction and the success of sinus conversion by the
      radiofrequency (RF) maze procedure for chronic AF. METHODS AND RESULTS: A total
      of 119 chronic AF patients undergoing valvular operations were included in this
      study. Sixty-one patients received RF and cryoablation to create lesions in both
      atria to simulate the surgical maze II or III procedure (RF maze II or RF maze
      III; 13 patients, group 1) or a modified maze pattern (RF maze "IV"; 48 patients,
      group 2). The other 58 patients who underwent valvular operations alone without
      the maze procedure served as control (group 3). At 3-month follow-up after
      operation, sinus rhythm was restored in 73%, 81%, and 11% of patients in groups
      1, 2 and 3, respectively. Preoperative left and right atrial sizes were not
      statistically significant predictors of sinus conversion by the RF maze
      procedure. However, as a result of postoperative reduction of atrial sizes,
      postoperative left atrial diameter was significantly smaller in patients who had
      sinus conversion by the RF maze procedure than in patients who did not regain
      sinus rhythm (45.0+/-7.0 mm vs 51.0+/-8.0 mm; P = 0.03). Postoperative right
      atrial area of patients who had sinus conversion by the RF maze procedure also
      was significantly smaller than that of patients who did not regain sinus rhythm
      (18.1+/-4.4 cm2 vs 28.5+/-8.2 cm2; P = 0.008). CONCLUSION: Atrial size reduction
      appears to predict the success of sinus conversion with the RF maze procedure
      used in conjunction with valvular surgery.

PMID- 11513436
TI  - Does size matter?

PMID- 11513437
TI  - Prevention of arterial thromboembolism in nonvalvular atrial fibrillation:
      validating molecular markers of risk stratification.

PMID- 11513438
TI  - Acquired pulmonary vein stenosis after radiofrequency catheter ablation of
      paroxysmal atrial fibrillation.
AB  - INTRODUCTION: Elimination of the initiating focus within the pulmonary vein (PV)
      using radiofrequency (RF) catheter ablation is a new treatment modality for
      treatment of drug-refractory atrial fibrillation. However, information on the
      long-term safety of RF ablation within the PV is limited. METHODS AND RESULTS: In
      102 patients with drug-refractory atrial fibrillation and at least one initiating
      focus from the PV, series transesophageal echocardiography was performed to
      monitor the effect of RF ablation on the PV. There were 66 foci in the right
      upper PV and 65 foci in the left upper PV. Within 3 days of ablation, 26 of the
      ablated right upper PVs (39%) had increased peak Doppler flow velocity (mean
      130+/-28 cm/sec, range 106 to 220), and 15 of the ablated left upper PVs (23%)
      had increased peak Doppler flow velocity (mean 140+/-39 cm/sec, range 105 to
      219). Seven patients had increased peak Doppler flow velocity in both upper PVs.
      No factor (including age, sex, site of ablation, number of RF pulses, pulse
      duration, and temperature) could predict PV stenosis after RF ablation. Three
      patients with stenosis of both upper PVs experienced mild dyspnea on exertion,
      but only one had mild increase of pulmonary pressure. There was no significant
      change of peak and mean flow velocity and of PV diameter in sequential follow-up
      studies up to 16 (209+/-94 days) months. CONCLUSION: Focal PV stenosis is
      observed frequently after RF catheter ablation applied within the vein, but
      usually is without clinical significance. However, ablation within multiple PVs
      might cause pulmonary hypertension and should be considered a limiting factor in
      this procedure.

PMID- 11513439
TI  - Activation patterns in the left atrium during counterclockwise and clockwise
      atrial flutter.
AB  - INTRODUCTION: Activation of the left atrium (LA) in patients with isthmus
      dependent right atrial flutter (AFL) has not yet been studied. The aim of this
      study was to analyze the activation patterns in the LA in patients with
      counterclockwise and clockwise AFL. METHODS AND RESULTS: The study population
      consisted of 12 patients (10 men and 2 women; mean age 61+/-13 years) with
      documented AFL and atrial fibrillation referred for ablation. The LA was mapped
      with a 64-electrode basket catheter inserted through a transseptal approach (10
      patients) or an open foramen ovale (2 patients). In patients with
      counterclockwise AFL (10 episodes), the LA was activated for a mean of 133+/-28
      msec. Two endocardial breakthroughs of earliest activity on the left side of the
      interatrial septum, separated in time by an interval of 38+/-15 msec, were
      observed in 9 episodes (90%). Two wavefronts originated from these breakthroughs,
      which activated the posterior and the anterior LA walls, respectively. In one
      patient, the entire LA was activated from the inferior breakthrough. In patients
      with clockwise AFL (five episodes), the LA activation time was 130+/-13 msec.
      During ongoing episodes, two early electrical breakthroughs, separated in time by
      an interval of 41+/-15 msec, appeared in the high anteroseptal and low
      posteroseptal LA regions. The superior wavefront that emerged from the high
      anterolateral LA region was the dominant activation pathway in 4 (80%) of 5
      episodes. CONCLUSION: In patients with AFL, the LA is activated by two wavefronts
      originating from the high anterior and the low posterior regions of the
      interatrial septum. The sequence of activation of these interatrial connections
      in counterclockwise or clockwise AFL and the conductive properties of the LA
      conduction pathways determine the activation patterns in the LA.

PMID- 11513440
TI  - Clinical outcome after radiofrequency catheter ablation of focal atrial
      fibrillation triggers.
AB  - INTRODUCTION: Ablative therapy for atrial fibrillation (AF) by targeting
      initiating triggers, usually in or around the pulmonary veins, has been reported
      by several centers. Evidence for an overall improvement in quality of life (QOL)
      and amelioration of symptoms is lacking. METHODS AND RESULTS: Seventy-one
      patients undergoing attempted ablation of focal AF were followed for 60+/-33
      weeks. QOL and symptom questionnaires were completed 1 month before and 6 months
      after electrophysiologic study. Twenty-three patients (32%) underwent
      electrophysiologic mapping but no ablation because of either insufficient or
      multifocal ectopy; the other 48 patients (68%) underwent attempted ablation.
      Sixteen of 48 patients (33%) undergoing ablation, or 16 (23%) of 71 on an
      intention-to-treat basis, were found at last follow-up to have persistent sinus
      rhythm without antiarrhythmic drugs. Patients who underwent mapping without
      ablation reported no improvements in any QOL or symptom score, whereas patients
      who had long-term successful ablation had significant improvements in all six QOL
      measures. Interestingly, patients who developed AF recurrence after ablation
      still reported significant improvements in 4 of 6 QOL measures. Four of 48
      patients (8.3%) undergoing ablation developed pulmonary vein stenosis.
      CONCLUSION: Paroxysmal AF can be treated successfully in some patients by
      ablating initiating triggers in the pulmonary veins; however, in our experience
      the recurrence rate (32/48 [68%]) and risk of pulmonary vein stenosis (8%) after
      ablation are high. Patients with recurrent AF after ablation of focal AF triggers
      have significant improvement in QOL and symptoms compared with before ablation.
      Patients and their physicians should carefully balance the risks and benefits
      before considering ablation.

PMID- 11513441
TI  - Ablation for atrial fibrillation: is the cure at hand?

PMID- 11513442
TI  - Prevention of chronic atrial fibrillation by pacing in the region of Bachmann's
      bundle: results of a multicenter randomized trial.
AB  - INTRODUCTION: Atrial pacing locations that decrease atrial activation and
      recovery time may be preferable in patients with a history of atrial arrhythmias.
      This multicenter prospective randomized study compared the efficacy of Bachmann's
      bundle (BB) region pacing to right atrial appendage (RAA) pacing in patients with
      recurrent paroxysmal atrial fibrillation (AF). METHODS AND RESULTS: Patients with
      standard pacing indications (n = 120, 70+/-11 years) were randomized to atrial
      pacing in either the RAA (n = 57) or BB region (n = 63). Implantation time was
      similar between groups (88+/-36 min [n = 38] for BB vs 83+/-34 min [n = 34] for
      RAA). No differences in pacing threshold, impedance, or sensing between BB and
      RAA groups were observed at implantation or after the 6-week, 6-month, and 1-year
      follow-up periods. Average length of follow-up was 12.6+/-7.4 months for the BB
      group and 11.8+/-8.0 months for the RAA pacing group. The percentage of atrial
      pacing was similar between groups (61%+/-34% RAA vs 65%+/-31% BB at 2 weeks after
      implant). BB atrial pacing significantly (P < 0.05) shortened p wave duration
      compared with sinus rhythm (123+/-21 msec vs 132+/-21 msec, n = 50) 2 weeks after
      implant. In contrast, p wave duration was longer during atrial pacing from the
      RAA position compared with sinus rhythm (148+/-23 msec vs 123+/-23 msec, n = 37).
      Additionally, p wave duration was shorter during BB pacing than during RAA
      pacing. Patients with BB pacing had a higher (P < 0.05) rate of survival free
      from chronic AF (75%) compared with patients with RAA pacing (47%) at 1 year.
      CONCLUSION: BB region pacing is safe and effective for attenuating the
      progression of AF.

PMID- 11513443
TI  - Alternate-site pacing as monotherapy for prevention of atrial fibrillation: is it
      here to stay?

PMID- 11513444
TI  - Defibrillation efficacy comparing a subcutaneous array electrode versus an
      "active can" implantable cardioverter defibrillator and a subcutaneous array
      electrode in addition to an "active can" implantable cardioverter defibrillator:
      results from active can versus array trials I and II.
AB  - INTRODUCTION: Placement of implantable cardioverter defibrillators (ICDs) has
      been simplified by using the shell of a pectorally implanted ICD as a
      defibrillation electrode in combination with an endocardial right ventricular
      defibrillation lead. However, a sufficiently low defibrillation threshold (DFT)
      cannot be obtained in a few patients. Therefore, alternative approaches were
      systematically tested in the Active Can versus Array Trial (ACAT). METHODS AND
      RESULTS: In the first of two prospective randomized studies, the DFT of a
      subcutaneous left dorsolateral array anode introduced from a pectoral incision
      was compared to that of a standard active can anode in 68 patients.
      Intraoperatively, the DFT was determined twice in each patient using either the
      active can or, in patients with a subcutaneous array lead, once with all three
      fingers and once omitting the middle finger of the array. The second prospective
      randomized study included 40 patients. DFT also was determined twice in each
      patient using an active can in a left pectoral position as anode alone and
      combined with a left dorsolateral array electrode with two fingers. In ACAT I,
      stored energy at DFT decreased from 13.1+/-7.7 J (active can) to 9.6+/-6.1 J
      (three-finger array lead) (P = 0.04), impedance decreased from 53+/-8 ohms to
      40+/-6 ohms (P < 0.0001). Omitting the middle finger of the array lead, stored
      energy at DFT increased by 0.9 J (P = 0.47) and impedance by 2 ohm (P < 0.0001).
      In ACAT II, DFT and impedance using an active can device were significantly lower
      when a two-finger array lead was added that decreased stored energy at DFT from
      10.1+/-5.2 J to 6.9+/-3.9 J (P = 0.001) and impedance from 56+/-5 1 to 42+/-5 l
      (P < 0.0001). CONCLUSION: In combination with a right ventricular defibrillation
      electrode, a left pectoral subcutaneous array lead improves defibrillation
      efficacy if used instead of, or in addition to, a left pectoral active can ICD
      device. Implantation of the array lead can be simplified by using two instead of
      three fingers, without a significant loss of defibrillation efficacy.

PMID- 11513445
TI  - Electrophysiologic characteristics of ventricular extrastimulation-induced
      dissipation of functional bundle branch block associated with supraventricular
      tachycardia.
AB  - INTRODUCTION: Linking-related anterograde functional bundle branch block during
      supraventricular tachycardia (SVT) is due to repetitive concealed retrograde
      conduction of impulses from the contralateral bundle branch and can be eliminated
      by a critically timed premature ventricular beat (PVB). We assessed the
      electrophysiologic characteristics of PVB-induced dissipation of functional
      bundle branch block during SVT. METHODS AND RESULTS: During SVT with functional
      bundle branch block, PVB was delivered from the right ventricular apex, scanning
      the tachycardia cycle length (CL) with 10-msec decrements in the coupling
      interval in 14 patients (3 AV nodal reentrant tachycardia and 11 orthodromic AV
      reciprocating tachycardia). Dissipation was achieved in group 1: functional right
      bundle branch block (RBBB) in 4, functional left bundle branch block (LBBB) in 4,
      and both functional RBBB and LBBB in 1 with a dissipation zone occupying 4% to
      13% (mean 8.5%) of the tachycardia CL. The outer limits were 22+/-16 msec and
      68+/-14 msec < tachycardia CL; the inner limits were 56+/-18 msec and 90+/-24
      msec < tachycardia CL for RBBB and LBBB, respectively (both P < 0.05).
      Dissipation could not be achieved in group 2 (4 RBBB and 1 LBBB) due to CL
      dependent bundle branch block and/or local ventricular refractoriness.
      CONCLUSION: During SVT, functional bundle branch block due to "linking" often can
      be dissipated by timely PVB delivered from the right ventricular apex within a
      narrow zone of the tachycardia CL. Our findings suggest that the dissipation zone
      is affected by the pattern of functional bundle branch block relative to the site
      of PVB delivery.

PMID- 11513447
TI  - Prolongation of activation-recovery interval over a preexcited region before and
      after catheter ablation in patients with Wolff-Parkinson-White syndrome.
AB  - INTRODUCTION: Preexisting changes in repolarization properties play an important
      role in T wave abnormalities (cardiac memory) after ablation in patients with
      Wolff-Parkinson-White (WPW) syndrome. However, no report has provided direct
      evidence for prolongation of action potential duration (APD) over a preexcited
      region before and after ablation. METHODS AND RESULTS: We studied 10 patients
      with ventricular preexcitation due to a left-sided accessory pathway (AP) (group
      M) and 12 patients with concealed left-sided AP (group C) to clarify prolongation
      of APD using activation-recovery intervals (ARIs) from epicardial and endocardial
      unipolar electrograms in patients with WPW syndrome. ARI was calculated from
      unipolar electrograms at the His bundle and the coronary sinus adjacent to the AP
      during atrial pacing (100 beats/min) before and 30 minutes after ablation. Before
      ablation, ARIs at the AP site were significantly longer in group M than in group
      C (255+/-21 msec vs 211+/-24 msec; P < 0.01), whereas ARIs at the His bundle did
      not differ between the two groups (255+/-20 msec vs 245+/-27 msec; P = NS). After
      ablation, group M showed no significant changes in ARIs at the AP and His bundle
      (256+/-19 msec and 253+/-15 msec) compared with before ablation. CONCLUSION: We
      found by direct analysis of ARIs from the epicardium that APD prolongation over
      the preexcited region was present before catheter ablation and persisted after
      catheter ablation. The gradual changes in repolarization properties, including
      APD prolongation after discontinuation of AP, may be one mechanism of cardiac
      memory after catheter ablation in patients with WPW syndrome.

PMID- 11513446
TI  - Usefulness of midodrine in patients with severely symptomatic neurocardiogenic
      syncope: a randomized control study.
AB  - INTRODUCTION: The efficacy of midodrine for the management of patients with
      neurocardiogenic syncope was assessed prospectively in a randomized control
      study. METHODS AND RESULTS: Patients who had at least monthly occurrences of
      syncope and a positive tilt-table test were included in the study. A total of 61
      patients were randomly allocated to treatment either with midodrine or with
      fluid, salt tablets, and counseling. Midodrine was given at a starting dose of 5
      mg three times a day and increased up to a dose of 15 mg three times a day when
      required. Midodrine was given during the daytime every 6 hours. Thirty-one
      patients were assigned to treatment with midodrine; the other 30 patients were
      advised to increase their fluid intake and were instructed to recognize their
      prodromes and abort the progression to syncope. Patients were followed-up for at
      least 6 months. A quality-of-life questionnaire was administered at the time of
      randomization and 6 months after. At the 6-month follow-up, 25 (81%) of 31
      midodrine-treated patients and 4 (13%) of the 30 fluid-therapy patients had
      remained asymptomatic (P < 0.001). One patient had to discontinue taking
      midodrine due to severe side effects and another six patients experienced minor
      side effects that did not require drug discontinuation. CONCLUSION: Midodrine
      appeared to provide a significant benefit in patients with neurocardiogenic
      syncope. To prevent recurrence of symptoms, dose adjustments were required in
      about one third of patients.

PMID- 11513448
TI  - Virtual electrode polarization leads to reentry in the far field.
AB  - INTRODUCTION: Our previous article examined cardiac vulnerability to reentry in
      the near field within the framework of the virtual electrode polarization (VEP)
      concept. The present study extends this examination to the far field and compares
      its predictions to the critical point hypothesis. METHODS AND RESULTS: We
      simulate the electrical behavior of a sheet of myocardium using a two-dimensional
      bidomain model. The fiber field is extrapolated from a set of rabbit heart fiber
      directions obtained experimentally. An S1 stimulus is applied along the top or
      left border. An extracellular line electrode on the top delivers a cathodal or
      anodal S2 stimulus. A VEP pattern matching that seen experimentally is observed
      and covers the entire sheet, thus constituting a far-field effect. Reentry arises
      from break excitation, make excitation, or a combination of both, and subsequent
      propagation through deexcited and recovered areas. Reentry occurs in cross-field,
      parallel-field, and uniform refractoriness protocols. For long coupling intervals
      (CIs) above CImake(min) (defined as the shortest CI at which make excitation can
      take place), rotors move away from the cathodal electrode and the S1 site for
      increases in S2 strength and CI, respectively. For cathodal S2 stimuli, findings
      are consistent with the critical point hypothesis. For CIs below CImake(min),
      reentry is initiated by break excitation only, and the resulting reentrant
      patterns are no longer consistent with those predicted by the critical point
      hypothesis. CONCLUSION: Shock-induced VEP can explain vulnerability in the far
      field. The VEP theory of vulnerability encompasses the critical point hypothesis
      for cathodal S2 shocks at long CIs.

PMID- 11513449
TI  - Atrial defibrillation thresholds of electrode configurations available to an
      atrioventricular defibrillator.
AB  - INTRODUCTION: Little investigation has been conducted to assess the atrial
      defibrillation thresholds of electrode configurations using electrodes designed
      for internal ventricular defibrillation (right ventricle [RV], superior vena cava
      [SVC], and pulse generator housing [Can]) combined with coronary sinus (CS)
      electrodes. We hypothesized that a CS-->SVC+Can electrode configuration would
      have a lower atrial defibrillation threshold than a standard configuration for
      defibrillation, RV-->SVC+Can. We also tested the atrial defibrillation thresholds
      of five other configurations. METHODS AND RESULTS: In 12 closed chest sheep, we
      situated a two-coil (RV, SVC) defibrillation catheter, a left-pectoral
      subcutaneous Can, and a CS lead. Atrial fibrillation was burst induced and
      maintained with continuous infusion of intrapericardial acetyl-beta-methylcholine
      chloride. Using fixed-tilt biphasic shocks, we determined the atrial
      defibrillation thresholds of seven test configurations in random order according
      to a multiple-reversal protocol. The peak voltage and delivered energy atrial
      defibrillation thresholds of CS-->SVC+Can (168+/-67 V, 2.68+/-2.40 J) were
      significantly lower than those of RV-->SVC+Can (215+/-88 V, 4.46+/-3.40 J). The
      atrial defibrillation thresholds of the other test configurations were RV+CS-
      >SVC+Can: 146+/-59 V, 1.92+/-1.45 J; RV-->CS+SVC+Can: 191+/-89 V, 3.53+/-3.19 J;
      CS-->SVC: 188+/-98 V, 3.77+/-4.14 J; SVC-->CS+ Can: 265+/-145 V, 7.37+/-9.12 J;
      and SVC-->Can: 516+/-209 V, 24.5+/-15.0 J. CONCLUSIONS: The atrial defibrillation
      threshold of CS-->SVC+Can is significantly lower than that of RV-->SVC+Can. In
      addition, the low atrial defibrillation threshold of RV+CS-->SVC+Can merits
      further investigation. Based on corroboration of low atrial defibrillation
      thresholds of CS-based configurations in humans, physicians might consider using
      CS leads with atrioventricular defibrillators.

PMID- 11513450
TI  - His-bundle parasystole masquerading as exercise-induced 2:1 atrioventricular
      block.
AB  - We describe a case of symptomatic pseudo-AV block due to His-bundle parasystole
      masquerading as exercise-induced 2:1 AV block. Electrophysiologic study revealed
      the presence of His-bundle parasystole, and the fluctuation of parasystolic cycle
      length could be explained by the concept of modulated parasystole. Modulated
      parasystole is a possible explanation for maintenance of stable 2:1 AV conduction
      at an atrial rate of specific range during exercise.

PMID- 11513451
TI  - Demonstration of the reentrant circuit of verapamil-sensitive idiopathic left
      ventricular tachycardia: direct evidence for macroreentry as the underlying
      mechanism.
AB  - The exact reentrant circuit of verapamil-sensitive idiopathic left ventricular
      tachycardia (ILVT) remains unclear. This case report demonstrates the reentrant
      circuit of ILVT. A 20-pole electrode catheter was placed along the left posterior
      fascicle during electrophysiologic study. ILVT was reproducibly induced by
      programmed ventricular stimulation. During the tachycardia, sequential diastolic
      potentials bridging the entire diastolic period were observed in the recordings
      from the electrodes positioned from left ventricular mid-septum to inferoapical
      septum. The slow conduction zone appeared to be composed of a false tendon in
      this patient. Entrainment of the ILVT from the right ventricular outflow tract at
      a different pacing cycle length revealed that a dominant conduction delay
      occurred at the proximal site of the slow conduction zone. Entrainment studies
      from several sites on the left ventricular septum confirmed that these sites
      where sequential electrical activity was recorded were included within the
      reentrant circuit. However, the left posterior fascicle itself seemed to be a
      bystander. This report provides the direct evidence of macroreentry as the
      underlying mechanism of this ILVT, adjacent to the left posterior fascicle.

PMID- 11513452
TI  - Mechanism of ventricular arrhythmias in the long QT syndrome: on hermeneutics.
AB  - Both the congenital and acquired long QT syndrome are due to abnormalities
      (intrinsic and/or acquired) of the ionic currents underlying repolarization. The
      prolongation of repolarization acts as a priming step for the generation of early
      afterdepolarizations. In the long QT syndrome, it also is associated with
      increased dispersion of repolarization. Focal early afterdepolarization-induced
      triggered beat(s) can infringe on the underlying substrate of inhomogeneous
      repolarization to initiate polymorphic reentrant ventricular tachycardia that
      sometimes has a characteristic twisting of the QRS axis, referred to as torsades
      de pointes.

PMID- 11513454
TI  - Respiration and initiation of atrial fibrillation.

PMID- 11513453
TI  - Repetitive, nonsustained wide QRS complex tachycardia: what is the tachycardia
      mechanism?

PMID- 11513455
TI  - Niche rad use.

PMID- 11513456
TI  - A litigation primer for the health physicist.
AB  - This primer presents a basic overview of legal terminology and theories that may
      be encountered by the health physicist relative to radiation-related litigation.
      Legal terms are defined, and the progression of a sample radiation injury claim
      is explained from the filing of a claim through the appeal process. The objective
      of the primer is to establish a basic foundation of legal concepts on which to
      build further understanding. The legal system is an arena with which most health
      physicists have essentially no familiarity or, at best, limited knowledge. The
      chances are increasing that health physics professionals may be involved in
      radiation injury litigation in some way, requiring a basic understanding of these
      concepts.

PMID- 11513457
TI  - An overview of the current state of radiation litigation.
AB  - Over the last three decades, radiation litigation has become a unique field of
      toxic tort litigation, with many new precedent setting decisions providing
      guidelines establishing how cases will be litigated in the future. This article
      will provide a summary of the status of the issues that are being litigated in
      radiation cases, and suggest recommendations on how pending issues should be
      resolved in the future.

PMID- 11513458
TI  - A radiation litigation causation analysis which achieves fairness to both
      litigants.
AB  - Very few, if any, radiation induced cancers should appear among nuclear workers
      in the United States. The existing safety standards and lifetime doses received
      under the operation of those safety standards are such that less than 1% of the
      cancers that appear in nuclear workers should be related to their occupational
      radiation exposure. This small numbers of valid claims is a tribute to the
      effectiveness of the federal safety standards and to the ALARA professional
      philosophy of achieving excellence in radiation protection which has marked the
      field of health physics since its inception.

PMID- 11513459
TI  - Documentation and log keeping: ensuring your work does what you intend it to do.
AB  - Maintaining regular documentation, such as a log-book, can be an organization's
      most important asset when dealing with radiation protection issues, both normal
      and abnormal. When an organization is faced with litigation, proper documentation
      of events can ensure that a record is acceptable and, by extension, that the data
      itself is acceptable. A record of events will not preclude litigation, nor will
      it guarantee that an organization will prevail in a court of law, but it will
      provide evidence and credibility that could favorably affect the outcome of
      litigation. An organization can ensure that the documents it creates and
      maintains are as effective as possible by being aware of the legal consequences
      of documenting events and taking appropriate steps to conform to standards for
      admission of documentation. Misconceptions about log keeping such as recording
      only events that are likely to result in litigation, rather than recording all
      events, can prevent a record from being admissible as evidence. Because of the
      amount of effort and time put into documentation, and the reliance placed on its
      contents, it is important for an organization to ensure that a record will do
      what it is intended to do, namely to accurately record activities. Issues
      discussed in this article include the legal basis of documentary evidence, what
      and what not to record, when and how to record it, and how to strengthen the
      records kept.

PMID- 11513460
TI  - The role of the expert witness: an update.
AB  - As in the past, the principle role of the scientist in the courtroom is to assist
      attorneys, judges, and jurors in understanding the complex scientific and
      technical issues before them. In the last decade, however, changes in the law and
      the increasing technical complexity of many disputes have introduced new factors
      that influence the preparation and presentation of expert testimony. The most
      significant change in the law regarding expert testimony is arguably the 1993
      Supreme Court ruling in Daubert vs. Merrell Dow Pharmaceuticals. Under Daubert,
      scientific evidence may be submitted to the jury if the judge finds that it rests
      on a reliable foundation and is relevant to the task at hand. Reliability and
      relevance replace the older requirement of "general acceptance by the scientific
      community," although "general acceptance" remains a factor in the consideration
      of reliability. The tests of reliability and relevance and their impact on the
      preparation of expert opinions are discussed in the context of increasingly
      complex radiation cases, with emphasis on cases involving teams of experts.

PMID- 11513461
TI  - Radon exposure and the risk of leukemia: a review of epidemiological studies.
AB  - Since the 1990's, several authors estimated that radon inhalation may deliver a
      small amount of irradiation to the red bone marrow, and consequently may increase
      the risk of leukemia in humans. The objective of this review is to conduct a
      critical analysis of epidemiologic results currently available concerning the
      relationship between radon exposure and the risk of leukemia. Nineteen ecological
      studies, six miner cohort studies, and eight case-control studies published
      between 1987 and 2000 are included in this review. The limitations associated
      with each of these studies are discussed. The results of the ecological studies
      are relatively concordant and suggest an association between radon concentrations
      and the risk of leukemia at a geographic level. But these ecological studies
      present important limitations, and some are only crude analyses. Moreover, the
      results of the cohort and case-control studies, based on individual data, do not
      show any significant association between radon exposure and leukemia risk. Our
      conclusion is that the overall epidemiologic results currently available do not
      provide evidence for an association between radon exposure and leukemia.

PMID- 11513462
TI  - Review of the ICRP tritium and 14C internal dosimetry models and their
      implementation in the Genmod-PC code.
AB  - Biokinetic models for tritium and 14C compounds, as described by various ICRP
      publications, have been incorporated into the Genmod-PC internal dosimetry code.
      This work reviews the models for tritium and 14C labeled compounds that the ICRP
      has formulated over several decades. The ICRP dosimetry prescribed for hydrogen
      and carbon radionuclides is fundamentally different from that recommended for
      other elements in that it is based on retention functions for whole body activity
      instead of compartmental biokinetic models. The ICRP recommends dosimetric
      methods for tritium and 14C compounds, ten of which are coded in Genmod-PC as
      compartmental models, namely, five tritium compounds, e.g., tritiated water,
      tritium gas, and five 14C compounds, e.g., carbon dioxide, carbon-labeled
      methane. The values of the Genmod-PC calculated dose coefficients were compared
      with the ICRP's values. It is shown how the dose coefficients for intakes of
      tritium and 14C compounds are affected by different interpretations of the
      methods recommended by the ICRP for two of the three classes of vapors and gases.
      Some aspects of the ICRP models, such as the percent oxidized, would benefit from
      reconsideration so as to produce tritium and 14C biokinetics that are less
      dependent on the radionuclide.

PMID- 11513463
TI  - Influence of gender differences in the carbon pool on dose factors for intakes of
      tritium and 14C-labeled compounds.
AB  - The ICRP's biokinetic models for five tritium-labeled and five 14C-labeled
      compounds (not including radiopharmaceutical compounds and excepting carbon
      monoxide) incorporate a compartment representing the body carbon pool. Using the
      ICRP models, as coded into the Genmod-PC internal dosimetry code, higher dose
      coefficients are calculated for females than for ICRP's Reference Man. The ICRP's
      committed effective dose coefficients for the ingestion of tritiated water and
      organically bound tritium by the adult male are 1.8 x 10(-11) and 4.2 x 10(-11)
      Sv Bq(-1), respectively. Using the Genmod-PC code, the corresponding dose
      coefficients for the adult female are 2.2 x 10(-11) and 6.2 x 10(-11) Sv Bq(-1),
      which are 25% and 46% greater than the adult male's. Similarly, the ICRP's dose
      coefficient is 5.8 x 10(-10) Sv Bq(-11) for an intake of organically bound 14C by
      the adult male, and the estimated dose coefficient using Genmod is 54% greater
      for the adult female. The carbon retention half-time for an average adult female
      is calculated as 51 d and that for an average adult male, 38 d; the latter is
      similar to the carbon half-time of 40 d recommended by International Commission
      on Radiological Protection (ICRP). The longer turnover time of whole body carbon
      in females is one factor that causes the dose coefficients for females to be
      higher than those of males; a second factor is the smaller whole body mass of
      ICRP's Reference Woman compared to Reference Man.

PMID- 11513464
TI  - Dose to lung from inhaled tritiated particles.
AB  - Tritiated particulate materials are of potential hazard in fission, fusion, and
      other tritium handling facilities. The absorbed fractions (fraction of energy
      emitted that is absorbed by the target region) are calculated for tritiated
      particles deposited in the alveolar-interstitial (AI) region of the respiratory
      tract. The energy absorbed by radiologically sensitive tissue irradiated by
      tritiated particles, in regions of the lung other than in the AI region, is
      negligible. The ICRP Publication 71 assumes the absorbed fraction is unity for
      tritium deposited in the AI region. We employed Monte Carlo methods in a model to
      evaluate the energy deposition in the wall of the alveolar sac from particles of
      tritiated beryllium, tritiated graphite, titanium tritide, tritiated iron
      hydroxide and zirconium tritide. For the five materials examined, the absorbed
      fraction in alveolar tissue ranged from 0.31 to 0.61 for particles of 1 microm
      physical diameter and 0.07 to 0.21 for 5 microm diameter particles. The dose to
      alveolar tissue, for an acute inhalation of tritiated particles by an adult male
      worker, was calculated based on the ICRP 66 lung model and the particle
      dissolution model of Mercer (1967). For particles of 5 microm activity median
      aerodynamic diameter (AMAD), the committed equivalent dose to alveolar tissue,
      calculated for the five materials, ranged from 32-42%, respectively, of the
      committed equivalent dose derived assuming the absorbed fractions were unity.

PMID- 11513465
TI  - Effective half-life of 131I in thyroid cancer patients.
AB  - The oral administration of radioactive 131I is a standard treatment for thyroid
      carcinoma. One consideration for this therapy is assuring that other people do
      not receive significant radiation exposure. In particular, federal and state
      regulatory authorities stipulate that no individual should receive more than 5
      mSv (500 mrem) effective dose-equivalent from the released patient. Patients
      receiving more than 1.11 GBq (30 mCi) of 131I were traditionally confined as in
      patients by regulation until their burdens of radioactivity fell below that level
      or until the external dose rates were less than 50 microSv (5 mrem) per hour at 1
      m. Recent regulatory guidance recommends the use of biological elimination as
      well as physical decay in calculating the confinement time to keep the effective
      dose-equivalent to members of the public less than 5 mSv. Analysis of a database
      of more than 250 administrations of 131I for thyroid cancer shows a median
      effective half-life of at least 14 h, with substantial variation. Thus, discharge
      criteria for radiation safety purposes should be calculated on the basis of
      individual measurements. The release of these patients should not always be as
      prompt as the guidance indicates. The results also challenge some long-used
      assumptions regarding iodine excretion in this patient population.

PMID- 11513466
TI  - Measurement of scatter factors for 4, 6, 10, and 23 MV x rays at scattering
      angles between 30 degrees and 135 degrees.
AB  - NCRP Report No. 49, published in 1976, describes how to calculate the shielding
      for the medical use of x rays and gamma rays for energies up to 10 MV, including
      primary, scattered, and leakage radiation. However, in that report, data for
      scattered radiation for linear accelerators exist only for 6 MV, and leakage
      radiation is assumed, incorrectly, to be equivalent to primary radiation. Since
      the publication of that report, linear accelerators with energies up to 25 MV
      have been widely used in the radiation therapy community. Thus, there is a need
      to measure additional data for all energies in the range 4-25 MV. In this study,
      measurements were made of the "a" factor for 4, 6, 10, and 23 MV x rays at
      scattering angles between 30 degrees and 135 degrees. The results show that the 6
      and 10 MV "a" factor data are consistent with published data, and the 23 MV data
      are also consistent with recently published data at 18 and 25 MV. The data show
      that, in general, the "a" factor decreases with energy; the exception is that 23
      MV data show a sharp increase at low scattering angles, much greater than at
      other energies.

PMID- 11513467
TI  - Rebuttal to Mossman's deconstruction of radiation benefits.

PMID- 11513468
TI  - New IAEA/OECD nuclear energy statistics.

PMID- 11513469
TI  - Different effects of lectins on the ligand binding of the NMDA receptors and
      sigma sites in rat brain hippocampus synaptic membranes.
AB  - The effects of the lectins concanavalin A, WGA, ricin, abrin, and the mistletoe
      lectins from Viscum album MLI, MLII, and MLIII on the binding of ligands of the
      NMDA and sigma receptors in rat hippocampus synaptic plasma membranes were
      investigated. Binding of [3H]MK-801, [3H]glutamate, [3H]5,7-DCKA, and [3H]glycine
      to the membranes was decreased by 40-60% after addition of galactose-specific
      lectins (mistletoe lectins MLI, MLII, ricin, abrin) at concentrations of 0.01
      mg/ml, but was not affected by the glucose- and mannose-specific lectin Con A, an
      acetylglucosamine-specific lectin WGA, or an acetylgalactosamine-specific lectin
      MLIII. The binding of [3H]SKF 10047 was decreased only in the presence of MLIII
      and did not change after addition of the other lectins. It is suggested that
      lectin-sensitive ligand binding sites of sigma- and NMDA receptors are located
      separately, and that the carbohydrate side chains of the sigma receptor do not
      participate in the modulation of the NMDA-receptor.

PMID- 11513470
TI  - Environmental light-darkness conditions induce changes in brain and peripheral
      pyroglutamyl-peptidase I activity.
AB  - To evaluate the influence of light and darkness on brain pyroglutamyl-peptidase I
      (pGluPI) activity, four experimental groups of rats were compared at the same
      time-point (10.00 h). Two groups were designed with a standard 12-12 h light-dark
      cycle: In group A, the lights were on from 7.00 h to 19.00 h, and the experiment
      was done under light conditions; in group B, the lights were on from 19.00 h to
      7.00 h, and the experiment was done under darkness conditions. Two additional
      groups were designed with nonstandard light-dark conditions: In group C, the
      animals were subjected to constant light, and the experiment was done under light
      conditions. In group D, animals were subjected to constant darkness, and the
      experiment was done under darkness conditions. Light (vs darkness) and standard
      (vs nonstandard) conditions produced significant changes on pGluPI activity in
      specific structures; the data suggested that endogenous substrates of pGluPI such
      as thyrotropin-releasing hormone and gonadotropin-releasing hormone, might be
      modified in parallel. There was left predominance in the retina under light
      conditions on a standard schedule (group A). The regional pattern of distribution
      of activity was similar in groups on a standard schedule (A vs B) and in groups
      tested under constant light-dark conditions (C vs D). However, this pattern
      differed between groups subjected to standard vs constant light-dark conditions
      (A and B vs C and D). These results support an influence of environmental light
      and darkness on pGluPI activity, which may reflect concomitant changes in its
      susceptible substrates and consequently in their functions.

PMID- 11513471
TI  - The effect of serotonin, its precursors and metabolites on brain glutathione-S
      transferase.
AB  - The isoelectric point and substrate specificity of the main isoform of
      glutathione-S-transferase (GST, EC 2.5.1.18) isolated from brain stem,
      hippocampus and parietal cortex of pig brain were determined. The effect of
      serotonin, its precursors (Try, 5-HTry), physiologically active derivative
      (melatonin) and final metabolite (5-HIAA) on the activity of this form was
      examined. Investigation indicated that serotonin did not affect the activity of
      GST in all studied regions of brain. The inhibitory effect of Try was stronger
      than that of 5-HTry, but weaker than the one expressed by melatonin and
      especially by 5-HIAA. Studies on the type of inhibition showed that Try,
      melatonin and 5-HIAA can compete for the active site with the electrophilic
      substrate but not with glutathione. Therefore precursors and endogenous
      derivatives of serotonin but not serotonin itself may affect the detoxification
      function of brain glutathione-S-transferase and increase the exposure of brain to
      toxic electrophiles.

PMID- 11513472
TI  - Activation of guanylate cyclase by natriuretic peptides in mouse pituitary AtT20
      cells is influenced by phosphorylation of ANP.
AB  - The discovery of free and membrane-bound ectokinases raises the question whether
      phosphorylation is another mechanism to modulate the action of distinct
      neuropeptides. Atrial-natriuretic-peptide (ANP) which is widespread found in the
      central nervous system (CNS) and involved in the modulation of stress reactions
      and emotional states like anxiety contains a recognition-motif for cAMP-dependent
      protein kinase A. We investigated the effect of phosphorylation of ANP and C-type
      natriuretic peptide (CNP), a related peptide without phosphorylation site, on
      their ability to activate their receptors in mouse pituitary AtT20 cells by
      measuring the formation of cyclic guanosinmonophosphate (cGMP). Phosphorylation
      with protein kinase A inactivated ANP. Coincubation experiments adding
      adenosintriphosphate (ATP), ATP-analogues or inhibitors of protein kinases to the
      medium pointed to the presence of an intrinsic protein kinase A like ectokinase
      activity on AtT20 cells. The activity of CNP was unaffected in these experiments.
      Phosphorylation by ectokinases may be a physiological mechanism to regulate the
      biological activity of ANP in different tissues, such as pituitary and CNS.

PMID- 11513473
TI  - L-DOPA decarboxylase association with membranes in mouse brain.
AB  - This work presents evidence on the association of active DDC molecules with
      membranes in mammalian brain. L-DOPA decarboxylase (DDC) is generally considered
      to be a cytosolic enzyme. Membrane-associated DDC was detected by immunoblotting
      and enzymatic assay experiments. DDC activity and immunoreactivity could be
      partially extracted from mammalian brain membranes by detergent. Fractionation of
      membranes by temperature-induced phase separation in Triton X-114, resulted in
      the recovery of membrane-associated DDC in separation phases where integral and
      hydrophobic membrane proteins separate. Treatment of membranes with
      phosphatidylinositol-specific phospholipase C or proteinase K, did not elute
      membrane-associated DDC activity, suggesting that a population of DDC molecules
      exist embedded within membranes. The elucidation of the functional significance
      of the enzyme's association with membranes could provide us with new information
      leading to the better understanding of the biological pathways that DDC is
      involved in.

PMID- 11513474
TI  - Intrauterine hypoxia-ischemia alters expression of the NMDA receptor in the young
      rat brain.
AB  - Effects of intrauterine hypoxia-ischemia (HI) on expression of the NMDA receptor
      subunits as well as on [3H]MK-801 binding of the NMDA receptor were studied in 1
      day to 30-day old rat brain. Intrauterine HI conditions were achieved on
      gestation day 17 by clamping the uterine vasculature for 30 min followed by
      removal of the clamps to permit reperfusion. As determined by reverse
      transcriptase polymerase chain reaction, prenatal HI significantly reduced mRNA
      expression of the NRI subunit of the NMDA receptor in the hippocampus of 4, 8,
      and 30-day old rat brains. NR2A and NR2B subunit mRNAs were expressed in the
      hippocampus and the cortex of both the control and the prenatal HI rat brains.
      Intrauterine HI did not significantly affect expression of either the NR2A or
      NR2B subunit mRNA. Consistent with the RT-PCR data, protein expression of the NRI
      subunit in the hippocampus, but not the cortex, of 21-day old prenatal HI rat
      brains was significantly decreased as compared to the control rat brain.
      Intrauterine HI also significantly reduced binding affinity, but not the number
      of binding sites, of the NMDA receptor to [3H]MK-801, a noncompetitive antagonist
      of the NMDA receptor, in the hippocampus of 21-day old rat brain. The overall
      results suggest that prenatal HI-induced reduction of NRI expression and the
      altered binding ability of the NMDA receptor in the young rat brain may
      contribute to other long-lasting effects of intrauterine HI that we reported
      previously.

PMID- 11513475
TI  - Transient focal cerebral ischemia down-regulates glutamate transporters GLT-1 and
      EAAC1 expression in rat brain.
AB  - Transient focal cerebral ischemia leads to extensive excitotoxic neuronal damage
      in rat cerebral cortex. Efficient reuptake of the released glutamate is essential
      for preventing glutamate receptor over-stimulation and neuronal death. Present
      study evaluated the expression of the glial (GLT-1 and GLAST) and neuronal
      (EAAC1) subtypes of glutamate transporters after transient middle cerebral artery
      occlusion (MCAO) induced focal cerebral ischemia in rats. Between 24h to 72h of
      reperfusion after transient MCAO, GLT-1 and EAAC1 protein levels decreased
      significantly (by 36% to 56%, p < 0.05) in the ipsilateral cortex compared with
      the contralateral cortex or sham control. GLT-1 and EAAC1 mRNA expression also
      decreased in the ipsilateral cortex of ischemic rats at both 24h and 72h of
      reperfusion, compared with the contralateral cortex or sham control. Glutamate
      transporter down-regulation may disrupt the normal clearance of the synaptically
      released glutamate and may contribute to the ischemic neuronal death.

PMID- 11513476
TI  - Implication of the extracellular disulfide bond on myelin protein zero
      expression.
AB  - Mutations in myelin protein zero (P0) are responsible for several peripheral
      neuropathies. We studied transport and membrane integration of the truncated P0
      mutants using transfected oligodendroglial cell line (Oln93). Starting with rat
      cDNA, we produced two P0 deletions. The first, called P0-Tyr contains a 66 amino
      acid deletion in the extracellular domain and a tyrosine at the new position 32.
      In the second, called P0-Cys, the tyrosine 32 is replaced by a cysteine. This
      replacement restores a disulfide bond in the extracellular domain. Our results
      show that P0 proteins, truncated or not, were expressed in the plasma membrane of
      the transfected cells. Transcription rates of both mutants were normal. However,
      P0-Tyr was detected in only 3-5% of the cells compared to the P0-Cys and the wild
      type. Thus, the disulfide bond in the extracellular domain is important for
      stability and correct addressing of the P0 protein.

PMID- 11513477
TI  - Changes in kynurenic, anthranilic, and quinolinic acid concentrations in rat
      brain tissue during development.
AB  - Kynurenic, anthranilic, and quinolinic acid, brain tissue concentrations and
      indoleamine 2,3-dioxygenase [EC 1 13.11.17] activity were determined in rat
      brain, during pre- and postnatal development. Quinolinic acid brain tissue
      concentration was significantly increased at birth as compared with the prenatal
      level, then it declined rapidly in the postnatal period. By the contrary,
      kynurenic and anthranilic acids brain tissue concentrations in rat brain were
      significantly lower at birth as compared with those found prenatally; then
      kynurenic acid concentration decreased in the first postnatal week and increased
      thereafter, while anthranilic acid concentration increased in the first postnatal
      week and decreased thereafter. Indoleamine 2,3-dioxygenase [EC 1 13.11.17]
      activity were found unchanged in pre and post natal rat brain. The described
      opposite changes in quinolinic and kynurenic acids concentrations, occurring in
      pre- and postnatal period, despite the lack of knowledge on the precise role
      played by these compounds on the different neurotransmitter systems in the brain,
      could be involved in brain ontogenetic development.

PMID- 11513478
TI  - Nitric oxide synthase inhibition by L-NAME prevents the decrease of Na+,K+-ATPase
      activity in midbrain of rats subjected to arginine administration.
AB  - In the present study we investigated the effect of acute administration of L
      arginine on Na(+),K(+)-ATPase and Mg(2+)-ATPase activities and on some parameters
      of oxidative stress (chemiluminescence and total radical-trapping antioxidant
      parameter-TRAP) in midbrain of adult rats. We also tested the effect of L-NAME on
      the effects produced by arginine. Sixty-day-old rats were treated with an acute
      intraperitoneal injection of saline (group I, control), arginine (0.8 g/kg)
      (group II), L-NAME (2 mg/kg) (group III) or arginine (0.8 g/kg) plus L-NAME (2
      mg/kg) (group IV). Na(+),K(+)-ATPase activity was significantly reduced in the
      arginine-treated rats, but was not affected by other treatments. In contrast,
      Mg(2+)-ATPase activity was not altered by any treatment. Furthermore,
      chemiluminescence was significantly increased and TRAP was significantly
      decreased in arginine-treated rats, whereas the simultaneous injection of L-NAME
      prevented these effects. These results demonstrate that in vivo arginine
      administration reduces Na(+),K(+)-ATPase activity possibly through free radical
      generation induced by NO formation.

PMID- 11513479
TI  - Regulated gene expression in glioma cells: a comparison of three inducible
      systems.
AB  - Transcription control systems enable experimental regulation of transgene
      expression in eukaryotic cells by application of specific repressors or inducers.
      Currently used inducible systems include tetracycline (tet-off), dimerizer and
      ecdysone systems. While numerous studies have utilized a single system, their
      comparative performance under identical conditions remains unclear. We therefore
      compared the efficiency of these three systems in C6 glioma cells by using
      transient transfection and the lacZ reporter gene. Highest induced activity was
      found with the ecdysone system, followed by tet-off and dimerizer systems. Both
      lowest repressed activity and highest regulation were revealed with the dimerizer
      system, followed by ecdysone and tet-off systems. Our data suggest that the most
      appropriate system depends on the experimental procedures, the application and
      the gene to be regulated.

PMID- 11513480
TI  - Involvement of p38 mitogen-activated protein kinase and apoptosis signal
      regulating kinase-1 in nitric oxide-induced cell death in PC12 cells.
AB  - Although nitric oxide (NO) plays key signaling roles in the nervous systems,
      excess NO leads to cell death. In this study, the involvement of p38 mitogen
      activated protein kinase (p38 MAPK) and apoptosis signal-regulating kinase-1
      (ASK1) in NO-induced cell death was investigated in PC12 cells. NO donor
      transiently activated p38 MAPK in the wild type parental PC12 cells, whereas the
      p38 MAPK activation was abolished in NO-resistant PC12 cells (PC 12-NO-R). p38
      MAPK inhibitors protected the cells against NO-induced death, whereas the
      inhibitors were not significantly protective against the cytotoxicity of reactive
      oxygen species. Stable transfection with dominant negative p38 MAPK mutant
      reduced NO-induced cell death. Stable transfection with dominant negative mutant
      of ASK1 attenuated NO-stimulated activation of p38 MAPK and decreased NO-induced
      cell death. These results suggest that p38 MAPK and its upstream regulator ASK1
      are involved in NO-induced PC12 cell death.

PMID- 11513481
TI  - Effect of neuropeptide-EI on the binding of [3H]SCH 23390 to the dopamine D1
      receptor in rat striatal membranes.
AB  - We have previously demonstrated that neuropeptide-EI, at high doses, stimulates
      the production of cAMP, in caudate putamen, through the activation of adenylate
      cyclase coupled to specific D1 receptors. The aim of the present work was to find
      evidences for a probable interaction between this neuropeptide and the dopamine
      D1 receptor in the mammalian central nervous system. The present data show that
      neuropeptide-EI, at high concentrations, affected both the maximum binding and
      the apparent affinity of [n-methyl-3H] (R)-(+)-8 chloro-2,3,4,5-tetrahydro-3
      methyl-5-phenyl-1H-3-benzazepin-7-ol hemimaleate to the dopamine D1 receptor in a
      concentration-dependent manner.

PMID- 11513482
TI  - Studies of posttranslational modifications in spiny dogfish myelin basic protein.
AB  - The objective of this investigation was to determine whether nonmammalian myelin
      basic protein contained charge isomers resulting from extensive posttranslational
      modifications as seen in mammalian MBP. Four charge isomer components from
      dogfish MBP have been isolated. These forms arise by phosphorylation and
      deamidation modifications. Components C1, C2 and C3 have been characterized. We
      are currently characterizing component C8. Dogfish MBP is less cationic than
      mammalian MBP and has about 50% lower mobility on a basic pH gel electrophoresis
      relative to human and to bovine MBP. The mammalian component C1, which is
      unmodified, is modified in the dogfish by phosphorylation. The reduced
      electrophoretic mobility is largely attributable to the charge reduction
      resulting from phosphorylation in serine 72, 83, and 120 or 121 in C1, and C3. In
      component C2, two or three phosphate groups were distributed among residues 134,
      138 and 139. It was found that dogfish amino acid residue 30 was a lysine residue
      and not a glutamate residue as reported in the literature.

PMID- 11513483
TI  - Synaptic vesicle acidification and exocytosis studied with acridine orange
      fluorescence in rat brain synaptosomes.
AB  - The acidification of synaptic vesicles (SV) in rat brain synaptosomes was studied
      using acridine orange (AO) as a fluorescent probe. In synaptosomal suspensions
      the AO fluorescence was partially quenched, indicating the presence of an acidic
      compartment. In permeabilized synaptosomes, the quenching was augmented by MgATP
      and was sensitive to concanamycin A, a specific inhibitor of the V-type H(+)
      ATPase known to be present in synaptic vesicles. Some ATP-dependent acidification
      was also observed without permeabilization, suggesting that a fraction of
      synaptosomes (ca. 15%) was unsealed, irrespective of the method used to prepare
      the synaptosomes (sucrose or Ficoll density gradient, sedimentation or
      flotation). Depolarization of synaptosomes with 30 mM KCl resulted in an
      immediate, albeit small, rise in AO fluorescence that was prevented by the
      removal of Ca(2+) or by substituting NaCl for KCl. This response is consistent
      with depolarization-evoked release of the acidic contents of an exocytosis
      competent pool of synaptic vesicles, representing ca. 5% of the total. No further
      AO release subsequent to the immediate phase was observed in depolarized
      synaptosomes, which indicates an extremely rapid reacidification. The results
      demonstrate that AO fluorescence is suitable for monitoring SV acidification
      within synaptosomes, and may be used to derive an independent estimate of the
      relative size of the immediately releasable SV pool. In addition, the use of AO
      might be advantageous for the assessment of synaptosomal integrity by comparing
      the ATP-dependent acidification in intact and permeabilized synaptosomes.

PMID- 11513484
TI  - Effects of CRH and ACTH administration on plasma and brain neurosteroid levels.
AB  - The 3alpha-hydroxy ring A-reduced metabolite of progesterone, 3alpha-hydroxy
      5alpha-pregnan-20-one (allopregnanolone) is among the most potent known ligands
      of the gamma aminobutyric acid (GABA) receptor, designated GABA-A, in the central
      nervous system. We determined by RIA serum levels of progesterone (PROG), 5-alpha
      dihidroprogesterone (DHP) and allopregnanolone in male and female rats after
      corticotropin releasing hormone (CRH) and adrenocorticotropin hormone (ACTH)
      administration. Allopregnanolone was undetectable in plasma and brain of control
      males but detectable in plasma and brain of males injected with CRH and ACTH and
      of control and similarly treated females. Allopregnanolone increased in the
      plasma and brain after CRH and ACTH administration in all cases. The data
      demonstrate that the administration of CRH plus ACTH results in a rapid increase
      of the neuroactive steroid allopregnanolone in the brain of males and females to
      levels known to modulate GABA-A receptor function. Thus, stress could regulate
      neurosteroid biosynthesis via the hormones ACTH and CRH.

PMID- 11513485
TI  - Modulation of the levels of NMDA receptor subunit mRNA and the bindings of [3H]MK
      801 in rat brain by chronic infusion of subtoxic dose of MK-801.
AB  - The effects of continuous infusion of NMDA receptor antagonist MK-801 on the
      modulation of NMDA receptor subunits NR1, NR2A, NR2B, and NR2C were investigated
      by using in situ hybridization study. Differential assembly of NMDA receptor
      subunits determines their functional characteristics. Continuous
      intracerebroventricular (i.c.v.) infusion with MK-801 (1 pmol/10 microl/h) for 7
      days resulted in significant modulations in the NR1, NR2A, and NR2B mRNA levels
      without producing stereotypic motor syndromes. The levels of NR1 mRNA were
      significantly increased (9-20%) in the cerebral cortex, striatum, septum, and CA1
      of hippocampus in MK-801-infused rats. The levels of NR2A mRNA were significantly
      decreased (11-16%) in the CA3 and dentate gyrus of hippocampus in MK-801-infused
      rats. In contrast to NR2A, NR2B subunit mRNA levels were increased (10-14%) in
      the cerebral cortex, caudate putamen, and thalamus. However, no changes of NR2C
      subunits in cerebellar granule layer were observed. Using quantitative ligand
      autoradiography, the binding of NMDA receptor ligand [3H]MK-801 was increased (12
      25%) significantly in almost all brain regions except in the thalamus and
      cerebellum after 7 days infusion with MK-801. These results suggest that region
      specific changes of NMDA receptor subunit mRNA and [3H]MK-801 binding are
      involved in the MK-801-infused adult rats.

PMID- 11513486
TI  - Some critical issues in caregiver intervention research.

PMID- 11513487
TI  - Racial and ethnic factors in dementia care-giving research in the US.

PMID- 11513488
TI  - Health and long-term care for people with Alzheimer's disease and related
      dementias: policy research issues.
AB  - Policy research into the service needs of persons with dementia had its origin
      looking at challenges confronting caregivers--extended hours of instrumental task
      assistance, social isolation, fatigue, depression--and how public policy might
      support informal care-giving while saving public expenditures from nursing home
      care. This paper, drawing on the experience of the Medicare Alzheimer's Disease
      Demonstration and other work, provides suggestions for extending care and
      financing considerations to include health care use and the medical management of
      chronic health conditions. Basic research is needed to document current use and
      risk factors, as is experimentation with clinical and other interventions
      designed to achieve desired quality of care and cost outcomes. This section of
      the paper will be of direct interest to both US and international readers. The
      second half of the paper reviews the US state role in regulating and financing
      nursing homes, home and community-based care, and residential care. All these
      sectors have high rates of staff turnover, staff shortages, and concerns with
      quality of care. The international community and US states provide naturally
      occurring opportunities for delivery system experimentation and innovation.
      Research taking advantage of these opportunities could greatly inform public
      policy.

PMID- 11513489
TI  - The health and long-term care policy challenges of Alzheimer's disease.
AB  - The growth of the aging population, the increasing ethnic and cultural diversity
      of that population, and the changing nature of Alzheimer treatment and care
      demand change in the financing and delivery of health and long-term care in the
      US. These challenges will require public policies that are well informed by
      behavioral, social, and health policy research. The issues fall into three broad
      categories, each of which raises questions for research: the cost of Alzheimer
      care, Medicare and health care policy, and long-term care policy including
      support of the appropriate role of family caregivers and meeting the need for
      affordable long-term care. The paper calls for a closer collaboration between the
      research community, policy makers and advocates to assure that science is
      addressing the most urgent policy questions and that relevant research is being
      translated and communicated to policy makers in a timely fashion.

PMID- 11513490
TI  - Alzheimer's disease and related dementias: important policy issues.

PMID- 11513491
TI  - Russian dolls and Chinese boxes: the ecology of Alzheimer's disease research.

PMID- 11513492
TI  - Comments on research in the social sciences pertaining to Alzheimer's disease: a
      more humble approach.
AB  - This paper suggests that social scientists should make greater efforts to study
      those questions that truly address the daily needs of the AD community; that they
      should be more creative in their approach to future care, especially with regard
      to the social implications of new anti-dementia drugs and other treatments that
      may alter the course of the disease; and that more research is needed with
      respect to end of life care, and the controversies surrounding the use of tube
      feeding and antibiotics.

PMID- 11513493
TI  - Including the person with dementia in family care-giving research.

PMID- 11513494
TI  - Implications of differential impacts of care-giving for future research on
      Alzheimer care.
AB  - As the primary caregivers for the millions afflicted with Alzheimer's disease,
      family members have been the focus of research for the past two decades.
      Differences in care patterns and deleterious effects of care provision have been
      clearly established. However, similar demands and hardships associated with care
      giving result in different consequences for different families. A greater
      understanding of the care-giving context and its determinants will enhance
      knowledge of the differential impacts of care-giving. The most critical
      determinant of care-giving context is the role relationship between the caregiver
      and the care recipient. Future research must address role relationship as the
      primary determinant of what care is provided by whom, and in what manner. This
      will enhance the understanding of specific caregiver outcomes and lead to optimal
      targeting of interventions. Future research must also focus on the interface
      between the family and other social institutions. Evidence calls into question
      the equity, quality, and capacity of the current system of care, which assumes
      that family care is best. It will be important for future studies to explore
      alternate options for long-term care policy. Families and patients will also
      benefit from studies that assess strategies to ensure an adequate labor pool of
      qualified formal caregivers.

PMID- 11513495
TI  - An overview of the social and behavioral consequences of Alzheimer's disease.

PMID- 11513496
TI  - Health care triads and dementia care: integrative framework and future
      directions.
AB  - Physicians are usually the first contact in the health care system for persons
      with dementia and their family caregivers. This paper provides a synopsis of
      research findings and knowledge gaps regarding interactions among these
      participants in the health care triad--primary care physicians, family
      caregivers, and persons with dementia. Research traditions that inform knowledge
      about health care triads and dementia care include: older patient-physician
      relationships; the stress-coping social-support health model that dominates
      family caregiver research; the social learning-self-efficacy model; and
      literature on the quality of medical care. An integrative framework is presented
      to illustrate how the quality of interaction in dementia care encounters may be
      influenced by specific characteristics of members of the health care triad.
      Domains of dementia care interaction include symptom diagnosis, symptom
      management, medication management, support service linkage, and emotional
      support. The integrative framework also links the quality of interaction in these
      domains with health-related outcomes relevant to each of the health care triad
      members. Most empirical research in this area has found that family caregivers
      are dissatisfied with many aspects of physicians' dementia care, but measurement
      techniques vary widely and little is known about how the quality of physician
      care is associated with health-related outcomes. Physician surveys have shown
      that they are least certain about the quality of support service linkage advice
      they provide. Virtually no research has examined how the person with dementia
      experiences medical care encounters with physicians and their family members.
      Much remains to be learned about the longitudinal experience of each member of
      the health care triad, and how the quality of dementia care encounters changes
      over the course of the disease process. In this era of rapidly expanding
      educational and support service interventions for persons with dementia and their
      family caregivers, as well as computer-based information about dementia care, the
      influence of these external factors on health care triad interactions and
      outcomes also remains to be studied.

PMID- 11513497
TI  - Family issues and the care of persons with Alzheimer's disease.

PMID- 11513498
TI  - New paradigms for guiding research, interventions and policies for family
      caregivers.

PMID- 11513499
TI  - The physical environment of the person with Alzheimer's disease.
AB  - A conceptual structure based on a set of 11 universal human needs is used as the
      basis for organizing a view of research methods appropriate to designing
      environments for people with dementia. The advantages and disadvantages of four
      general approaches are discussed: consumer surveys, direct behavior observation,
      expert judgments, and experimental designs. All are found wanting, though clearly
      worth pursuing. Systematic qualitative observational methods are suggested as a
      mode for generating and organizing user-friendly data for designing environments
      for people with dementia.

PMID- 11513500
TI  - Human factors and environmental support in Alzheimer's disease.
AB  - Cognitive aging research suggests that environmental support can minimize memory
      failures in older adults. Similarly, designers of dwellings for frail and
      dementing older populations try to provide prosthetic environments to support
      greater independence. We review some of these research issues and design
      practices from a human factors perspective. Early in the disease process training
      approaches may be most effective, whereas later on there will need to be more
      reliance on effective design. We also suggest a framework for optimizing design
      across stakeholders and discuss some public policy issues.

PMID- 11513501
TI  - Discovering the person with Alzheimer's disease: cognitive, emotional and
      behavioural aspects.
AB  - The person-centred approach to dementia care emerges from a new emphasis on the
      experience of the person with dementia. The person is seen as attempting to
      manage and cope with their difficulties, through a variety of coping mechanisms.
      Some are able to seek to maximize their cognitive capacities, and there are a
      number of strategies now available to assist in this process. However, the
      emotional aspects merit increased attention, with more awareness needed of the
      range of powerful emotions that may be present, and of the possibility of
      therapeutic interventions to alleviate symptoms of anxiety and depression. Many
      of the difficult behaviours seen in dementia may be understood more fully with an
      appreciation of their emotional underpinning, in feelings of anger, fear,
      insecurity and hopelessness. The interaction between caregiver strain and
      challenging behaviour also merits further exploration. The person-centred
      approach has many implications for practice, as well as for research. The
      perspective of the person with dementia, and outcomes reflecting that
      perspective, must be represented in research studies in dementia care.
      Caregivers, whether family members or paid workers, require additional support in
      order to recognize the person's needs and to meet them in ways which enable the
      person's identity and full human value to be upheld.

PMID- 11513502
TI  - The physical and social environment of the person with Alzheimer's disease.

PMID- 11513503
TI  - Environmental design for Alzheimer's disease: a quality of life issue.

PMID- 11513504
TI  - Developing and evaluating community based intervention programs for Alzheimer's
      patients and their caregivers.
AB  - Innovative community based social and behavioral interventions for individuals
      suffering from Alzheimer's disease and their family caregivers have increased
      substantially in creativity and recognition over the years. However, the
      commitment to the scientific design and evaluations of these programs has not
      followed suit. The goal of this paper is to explicate the benefits of a
      systematic approach to the design and evaluation of intervention programs with
      the challenges of the Alzheimer's dyad in mind. Because of the unique nature of
      the disease, Alzheimer's programs must flexibly apply existing intervention and
      evaluation techniques to program designs which accommodate the degenerative
      course of the disease and the unique strain experienced by family caregivers.
      Using existing literature as a vehicle to illustrate how successful and
      unsuccessful programs have addressed these goals, the paper stresses the need for
      design and evaluations which apply creative and robust treatments, but do not
      compromise scientific rigor.

PMID- 11513505
TI  - Identification and assessment of effective services and interventions: the
      nursing home perspective.
AB  - In the past decade, researchers across the world have published a great number of
      studies on the care of nursing home residents with dementia. Investigations have
      concentrated on such important subjects as special care units, staff training,
      functional performance, and problem behaviors. However, most of the studies have
      lacked the rigor needed to establish the treatments that they tested as standards
      of care, according to criteria from the American Academy of Neurology. Without a
      solid scientific foundation, researchers in the USA have found it difficult to
      offer authoritative advice to policy makers and advocacy groups. This article
      will discuss some theoretical and methodological issues of research that require
      attention to fortify the scientific foundation. Topics include theoretical and
      definitional inconsistencies, sampling issues, limitations related to data
      collectors, the need for greater specificity of interventions, and outcome
      measures. The article will continue with an overview of areas that need further
      refinement and development. It will focus on combining basic and clinical
      sciences, combining behavioral and pharmacological research, combining clinical
      and health services research, reconceptualizing meaningful activity, palliative
      care in advanced dementia, certified nursing assistant training issues, and
      family training issues. The article will conclude with recommendations to
      establish collaborative research enterprises among existing organizations in the
      USA.

PMID- 11513506
TI  - Failure to thrive in babies with cleft lip and palate.
AB  - We established the frequency of failure to thrive (FTT) in children undergoing
      primary cleft procedures by using growth charts and standard-deviation scores.
      Initially, 147 babies with cleft lip and/or palate undergoing 186 primary lip-and
      palate repairs were studied between 1993 and 1996. Rates of FTT were categorised
      according to cleft type. There was an increasing rate of FTT from 32% for
      unilateral cleft lip and palate to 38% for bilateral cleft lip and palate to 49%
      for cleft palate. There was a high incidence of FTT in palatal clefts, especially
      if these were associated with a syndrome or anomaly (P= 0.001). The incidence of
      FTT with the Pierre Robin sequence was 100%. In view of the high rates of FTT,
      two changes were instituted: a feeding-support nurse was appointed to supervise
      and monitor patients at risk and all patients with the Pierre Robin sequence had
      supervised airway management. Thereafter, the incidence of FTT was prospectively
      studied in 68 babies undergoing 84 primary procedures between 1997 and 1999.
      There was a decrease in the incidence of FTT in comparison with the earlier
      cohort (9% for unilateral cleft lip and palate, 20% for bilateral cleft lip and
      palate, 26% for cleft palate). There was a significant decrease in the incidence
      of FTT in the group with the Pierre Robin sequence, from 100% to 40%. As a result
      of the provision of a feeding-support nurse and airway management of patients
      with the Pierre Robin sequence, the incidence of FTT was reduced and the audit
      loop closed.

PMID- 11513507
TI  - Adenoid cystic carcinoma of the head and neck.
AB  - Adenoid cystic carcinoma (ACC) is a rare malignant tumour believed to arise from
      the epithelial cells of mucous-secreting glands. It is a slow-growing but
      aggressive tumour with a propensity for perineural invasion. A 10 year review of
      45 patients (19 males and 26 females with a median age of 56 years) treated for
      ACC at a single institution between 1989 and 1999 was performed to analyse
      factors involved in treatment failure, local control, treatment-related morbidity
      and mortality. The data collected were treated for survival curves according to
      the Kaplan-Meier method and the log-rank test was used to assess the statistical
      significance of the various groups. The overall survivals at 3 years and 5 years
      were 71% and 65%, respectively, while the disease-free survivals at 3 years and 5
      years were 73% and 63% respectively. Out of the 45 patients, only six had local
      recurrences, yielding an 87% locoregional freedom from relapse; 16 patients
      (35.6%) developed distant metastases, with the lung (8/16) being the commonest
      site. Patients treated for tumours of the nose and paranasal sinuses experienced
      more morbidity than those with tumours at other sites. Positive margins,
      perineural invasion and solid histology of ACC were associated with increased
      morbidity and treatment failure. Patients treated with combined therapy did
      better than those who underwent a single treatment modality.

PMID- 11513508
TI  - The prevention of haematoma following rhytidectomy: a review of 1078 consecutive
      facelifts.
AB  - Haematoma remains the most common complication of rhytidectomy and can lead to
      prolonged facial oedema or skin necrosis. The factors leading to haematoma
      formation remain unclear, and studies establishing causal relationships are
      lacking. The aim of this study was to determine which parameters were
      significantly associated with haematoma formation in a consecutive series of
      facelifts performed by two high-volume operators. The records of 1078 patients
      who underwent facelifting between 1994 and 1999 were reviewed and the parameters
      associated with haematoma formation were investigated using multivariate
      statistical analysis. In this series of 1078 patients, 45 haematomas occurred
      (4.2%). Analysis revealed significant associations between haematoma formation
      and anterior platysmaplasty (P= 0.009), systolic pressure (P= 0.02), gender (P=
      0.03), aspirin or non-steroidal anti-inflammatory intake (P= 0.04) and smoking
      (P= 0.049). In addition the relative risk of each parameter was calculated. This
      allowed the haematoma risk for individual patients to be calculated and haematoma
      prone patients were identified preoperatively. This is the first study to
      establish independent statistical risk factors for haematoma after rhytidectomy
      and to present a scoring system that calculates the haematoma risk
      preoperatively. The implications of these findings and possible measures for the
      prevention of haematoma are also presented.

PMID- 11513509
TI  - Deep circumflex iliac perforator flap with iliac crest for mandibular
      reconstruction.
AB  - The deep circumflex iliac myocutaneous perforator (DCIP) flap with iliac crest
      was used to reconstruct oromandibular defects in 10 patients. In seven of the
      patients a dominant perforator was found preoperatively using a Doppler
      flowmeter; in five of these seven patients a DCIP flap was successfully
      transferred. In two of the seven patients the dominant perforators were too
      narrow: one patient underwent a standard osteocutaneous flap transfer and one
      patient underwent a second flap transfer. In three patients no dominant
      perforator was found before or during surgery. The freedom of the DCIP flap from
      the harvested iliac crest facilitates correct positioning. However, to ensure
      that the DCIP flap can be safely elevated, the presence of perforators must be
      confirmed preoperatively. Even when a perforator has been identified, complicated
      dissection may be necessary. We stress the importance of a thorough knowledge of
      the anatomy of second flaps and of obtaining informed consent to use them.

PMID- 11513510
TI  - Bimaxillary osteodistraction for the treatment of facial asymmetry in adults.
AB  - Nine patients with hemifacial microsomia or facial asymmetry were treated between
      April 1998 and November 1999. The ages of the patients ranged from 21 years to 45
      years (mean: 24.6 years); six were female and three were male. The follow-up
      period ranged from 6 months to 24 months (mean: 15.3 months). The operative
      procedure was based on Ortiz Monasterio's simultaneous mandibular and maxillary
      distraction technique. This technique frees only the pterygo-maxillary junction
      of the affected side, thereby leaving the nasal septum and the pterygo-maxillary
      junction of the unaffected side intact. It also uses an external corticotomy on
      the mandible. In contrast, we modified Ortiz Monasterio's method by using a
      complete LeFort I osteotomy with both a complete separation of the pterygo
      maxillary junction and a mandibular osteotomy to avoid any resistance during
      distraction. In one patient with scleroderma and severe atrophy of the mandible
      and soft tissue on the right side of the face, a free scapular osteocutaneous
      flap was used; 1 month later we performed simultaneous distraction of the maxilla
      and transfer of the scapula bone to the mandible. In one patient with hypoplasia
      of the zygoma, zygoma expansion was also performed simultaneously. Bidirectional
      distraction was performed in one patient and intraoral devices were applied in
      three patients. After a latent period of 5 days, distraction was performed at a
      rate of 1 mm per day. After a consolidation period of 6-8 weeks, the
      intermaxillary fixation and distraction devices were removed. Preoperatively, the
      deviation of the occlusal plane ranged from 8degrees to 13 degrees (mean: 10.5
      degrees); the distraction distance ranged from 7 mm to 17 mm (mean: 13 mm). In
      two patients there was radiologic evidence of relapse 6 months after distraction,
      but no significant change in facial appearance was observed. Seven patients
      maintained a stable preoperative occlusal relationship and the preoperative
      lateral open bite was improved postoperatively in two patients. The postoperative
      occlusal plane was between 0 degrees and 1 degree in every case.

PMID- 11513511
TI  - Nasolabial flaps in oral reconstruction: an analysis of 224 cases.
AB  - The nasolabial flap is a simple option for the reconstruction of selected oral
      defects. Though its use in floor-of-mouth reconstruction has been described,
      other uses in the oral cavity have not been studied extensively. We present a
      series of 224 oral malignancies where the nasolabial flap was used for
      reconstruction after surgical excision.

PMID- 11513512
TI  - Ear-lobe keloids: treatment by a protocol of surgical excision and immediate
      postoperative adjuvant radiotherapy.
AB  - There is no universally agreed policy for treating keloid scars of the ear lobe
      following piercing. We treated 35 patients (34 women) for high-risk ear-lobe
      keloids; the average age was 24 years (range: 16-44 years). All had failed to
      respond to prior treatment with massage and silicone, and corticosteroid
      injection. The keloids were excised extralesionally and the defects were closed
      with interrupted prolene sutures. The operative scar was covered with topical 2%
      lignocaine-0.25% chlorhexidine sterile lubricant gel under a transparent adhesive
      dressing. Adjuvant postoperative radiotherapy of 10 Gy, applied as 100 kV photons
      (4 mm high-voltage therapy (HVT) Al), was given within 24 h of surgery. All
      keloid scars were controlled at 4 weeks' follow-up. At 1 year, three out of 34
      cases followed up had relapsed (probability of control: 91.2%). At 5 years, a
      further four out of the remaining 31 patients had relapsed (cumulative
      probability of control at 5 years: 79.4%). There were no cases of serious
      toxicity.

PMID- 11513513
TI  - Zimmer splintage: a simple effective treatment for keloids following ear
      piercing.
AB  - An auricular keloid occurring following ear-piercing remains a difficult
      condition to treat. Various treatments have been described, with different
      reported degrees of success. Pressure therapy has been shown to be an effective
      treatment for auricular keloids, although the devices used have not all been
      universally accepted. We assessed 30 patients, between 1989 and 1999, who had
      been fitted with pressure devices made from Zimmer splints. There was a 50% or
      greater reduction in the size of each keloid when assessed at 1 year. Zimmer
      splints are cheap, readily available, easily moulded to fit the patient and can
      be decorated so that they can be worn as earrings.

PMID- 11513514
TI  - Inflammatory-cell subpopulations in keloid scars.
AB  - The aim of this study was to investigate the contribution of lymphocytes and
      macrophages to keloid scarring by morphologically characterising inflammatory
      cell subpopulations in keloid scars in comparison with normal skin. We took 3mm
      punch biopsies from the anterior forearms of eight normal healthy volunteers.
      Eight keloid scars were excised using an intralesional technique. All tissue was
      snap frozen in liquid nitrogen and serial sections were stained with a panel of
      anti-inflammatory cell monoclonal antibodies. The numbers of macrophages and
      lymphocytes and the proportions of the subpopulations were compared. Higher
      numbers of both macrophages and lymphocytes were found in keloid dermis (P=0.01
      and P=0.02, respectively (Mann-Whitney U -test)). There was no significant
      increase in the expression of the lymphocyte-activation markers, CD25 and CD27.
      However, there was a significantly higher CD4(+):CD8(+)(Th:Ts) ratio (P= 0.046)
      in keloid tissue. This suggests that an imbalance in these inflammatory cell
      subpopulations may contribute to keloid scarring in man.

PMID- 11513515
TI  - The impact of intraoperative hypotension on the development of wound haematoma
      after breast reduction.
AB  - A wound haematoma occurring after breast reduction may need to be drained
      surgically, and may prolong both hospital stay and the total recovery time
      following surgery. Intraoperative hypotension has been implicated in the
      development of various complications, but has not been previously studied in
      relation to breast reduction. A retrospective analysis of 238 breast reductions
      was performed with the aim of identifying risk factors for the development of
      wound haematoma after breast reduction. The operative time was divided into three
      equal periods and, in our experience, haemostasis was achieved in the middle
      period. In our series, 16 patients developed a postoperative wound haematoma;
      only four patients required operative evacuation (1.7%). Subcutaneous heparin
      prophylaxis, the level of the surgical team and the weight of tissue resected did
      not significantly affect the likelihood of wound haematoma. The lowest and the
      peak values of systolic blood pressure and the mean blood pressure (diastolic +
      1/3 pulse) were significantly lower in the middle period of the operation in
      patients who developed a haematoma P values: 0.012, 0.021 and 0.005,
      respectively). Univariate logistic regression analysis showed the same
      significant findings (P values: 0.0014, 0.021 and 0.0059, respectively).
      Multivariate stepwise logistic regression showed that the lowest systolic blood
      pressure in the middle period was significantly lower in the haematoma group than
      in the non-haematoma group (P= 0.0007). Intraoperative hypotension in the middle
      period of the operation, which is usually the period when haemostasis is
      achieved, is associated with the development of postoperative wound haematoma.

PMID- 11513516
TI  - Sensory recovery after reconstruction of defects of long fingertips using the
      pedicled V flap.
AB  - The pedicled V-flap technique was used to repair varying degrees of injury to the
      fingertip in 29 patients. The technique is described, together with the results
      of static two-point discrimination tests 1 month and 3 months after surgery. The
      sensation in the flaps reached near-normal levels after 3 months in all patients.
      Although statistically significant, the difference in the results at 1 month and
      3 months postoperatively was minimal.

PMID- 11513517
TI  - Waterproofing in hypospadias: a refinement of the two-stage reconstruction.
AB  - A new technique for 'waterproofing' during the second stage of a two-stage
      hypospadias repair is described. It is simpler and involves less tissue
      dissection than other waterproofing techniques. The senior author has used it
      over a period of 6 years as standard practice. The technique has been used in a
      total of 24 cases, in which the fistula rate was 8% (two cases).

PMID- 11513518
TI  - Grafting of large pieces of human reconstructed skin in a porcine model.
AB  - Present techniques can save about 25% of patients burnt over more than 90% of
      their body surface. However, problems of functional and aesthetic repair arise,
      which are often resolved only by major therapeutic procedures. Current advances
      in skin substitutes permit the cultivation, from a skin biopsy, of large surfaces
      of in vitro human reconstructed skin (HRS). Our model, obtained by the co-culture
      of fibroblasts and keratinocytes on a dermal substrate composed of collagen
      glycosaminoglycan-chitosan, reproduces, in vitro, a tissue close to human skin,
      which could play a role in reconstructive surgery. The objectives of this
      experiment were to assess whether it is possible to perform large HRS grafts and
      to evaluate the preliminary cosmetic results. We used four immunosuppressed
      female pigs. Full-thickness skin resections of 50-100 cm(2)were performed on the
      dorsa of the animals. The defects were grafted with between one and six pieces of
      HRS under tied-over dressings. At day 14, we found a soft and smooth surface of
      good transparent healthy pink skin, which was very easy to distinguish from the
      surrounding tissues. The junctions between different pieces of living skin were
      not visible. Immunohistological studies with specific anti-human keratin 14
      antibodies confirmed the graft take: 7 days after grafting the human epidermis
      was attached to the living dermis and showed good organisation with a basal cell
      layer and suprabasal cells; 28 days after grafting the human epidermis seemed to
      be replaced by pig epidermis. This study highlights the possibility of grafting
      large surfaces with HRS using a routine operating technique.

PMID- 11513519
TI  - A conservative surgical approach to the treatment of 'locally invasive' lentigo
      maligna melanoma of the face.
AB  - Lentigo maligna has the potential for malignant change, and is managed in many
      cases by wide local excision. However, there are clinical situations in which
      aggressive surgical management is inappropriate or unsuccessful. We present three
      such cases, in which a more conservative surgical approach was adopted and
      maintained over several decades.

PMID- 11513520
TI  - Long-term results of surgical excision and skin grafting for a giant hairy naevus
      of the face: time for a return to conventional wisdom?
AB  - In a publication climate demanding modern innovative treatments for congenital
      giant hairy naevi, we report a case with excellent long-term results following
      early surgical excision and split-thickness skin grafting.

PMID- 11513521
TI  - Endoscopic-assisted transaxillary removal of a midline anterior epidermoid cyst.
AB  - A 3-year-old boy presented with a 3 x 3 cm dermoid cyst in the midline of the
      anterior chest wall. This was successfully removed, using an endoscopic-assisted
      technique, through a single incision placed in the anterior axillary fold,
      avoiding the need for a mid-sternal incision. This technique and its application
      to paediatric soft-tissue surgery are discussed.

PMID- 11513522
TI  - Coverage of an ischial pressure ulcer with an interpolated contralateral
      posterior thigh fasciocutaneous flap.
AB  - The ipsilateral posterior thigh flap has become one of the workhorses for the
      closure of ischial pressure ulcers. We treated a 40-year-old paraplegic patient
      with a right ischial pressure ulcer, in whom all ipsilateral flap options had
      been expended or were precluded by scars. A contralateral left posterior thigh
      fasciocutaneous flap interpolated subcutaneously across the midline provided
      successful coverage.

PMID- 11513524
TI  - Pharyngoplasty and the risk of variant CJD transmission.

PMID- 11513523
TI  - Eyelid reconstruction using a hard palate mucoperiosteal graft combined with a V
      Y subcutaneously pedicled flap: palatal versus buccal mucosal grafts.

PMID- 11513525
TI  - Intraoperative photography.

PMID- 11513526
TI  - The use of the harmonic scalpel for glossectomy.

PMID- 11513527
TI  - Cutaneous verrucous carcinoma.

PMID- 11513528
TI  - The use of digital imaging in the assessment of skin lesions.

PMID- 11513529
TI  - Reaction in a red tattoo in the absence of mercury.

PMID- 11513530
TI  - Preoperative surgical skin marking in plastic surgery.

PMID- 11513531
TI  - The contralateral superficial inferior epigastric artery flap as a backup in
      breast reconstruction.

PMID- 11513532
TI  - Breast reduction in the 'sitting-up' position.

PMID- 11513533
TI  - One-stage technique for shortening the vertical wound in vertical-scar
      mammaplasty.

PMID- 11513534
TI  - Pre-existing venous disease and the gastrocnemius muscle flap.

PMID- 11513535
TI  - Surgical simulation in plastic surgery.

PMID- 11513536
TI  - Allis forceps: notes on the inventor.

PMID- 11513538
TI  - ICOS costimulation: is it the key to selective immunotherapy?

PMID- 11513539
TI  - Costimulation of memory T-cells by ICOS: a potential therapeutic target for
      autoimmunity?
AB  - Approaches that target costimulatory receptors are independent of T-cell receptor
      specificity and may be useful for T-cell-mediated diseases in which the antigens
      involved are not well defined. However, the proper costimulatory pathways need to
      be targeted. For example, therapies for human T-cell-mediated diseases need to be
      effective against previously activated memory cells. In this review, we use
      autoimmune demyelination as a paradigm for established immune-mediated
      pathogenesis. Studies with the human disease multiple sclerosis and the rodent
      model experimental autoimmune encephalomyelitis have suggested that the
      effectiveness of CD28 blockade, as a therapeutic strategy for established
      autoimmune demyelination, may be limited. ICOS, a receptor that appears to be
      involved in the costimulation of previously activated T-cells, may be an
      attractive alternative.

PMID- 11513540
TI  - Detection of intracellular phosphorylated STAT-4 by flow cytometry.
AB  - The convergence of innate and adaptive immunity is critical for host defense,
      allowing for early protection and the generation of specific responses. STAT-4 is
      at that point of convergence, unifying the IFNalpha and IL-12 pathways.
      Activation of STAT-4 is crucial to T cell polarization, B cell and NK cell
      activation, and the control of intracellular pathogens. However, techniques to
      detect phosphorylated STAT-4 are cumbersome and require many cells. We have
      developed a flow cytometric detection technique to investigate IL-12 signaling in
      human peripheral blood mononuclear cells. Using different polyclonal antibodies
      that recognize either total STAT-4 protein or tyrosine-phosphorylated STAT-4, we
      can easily detect IL-12 and IFNalpha signaling in PHA/IL-2 blasts derived from
      peripheral blood lymphocytes. This technique not only allows us to evaluate IL-12
      signaling, but it is also less time consuming and labor intensive than
      alternative methods. Using this flow cytometry-based method, we should be able to
      detect patients with defects in IL-12 receptor signal transduction, who typically
      present with disseminated nontuberculous mycobacterial infections.

PMID- 11513541
TI  - ICOS ligand costimulation is required for T-cell encephalitogenicity.
AB  - The interaction of ICOS with its ligand on APC provides a costimulatory signal to
      previously activated T-cells. In these studies, we blocked the ICOS:ICOS ligand
      interaction with ICOS-Ig during the in vitro activation of MBP-reactive
      transgenic CD4(+) T-cells. The presence of ICOS-Ig in these cultures inhibited
      the ability of the transgenic T-cells to transfer EAE, although they entered the
      brains of the recipient mice. ICOS-Ig increased apoptosis in the transgenic T
      cells, especially in the memory population. This enhanced apoptosis was
      accompanied by an increase in the BAX/BCL-2 mRNA ratio. ICOS-Ig did not prevent
      IL2 production, demonstrating that IL-2 production is ICOS ligand independent.
      IFN-gamma and IL-10 production by the transgenic T-cells, however, was
      suppressed. Finally, ICOS-Ig injection into mice after the first signs of EAE
      ameliorated clinical disease. Therefore, ICOSL provides a signal distinct from
      CD28 costimulation that is required for the activation and viability of
      encephalitogenic T-cells.

PMID- 11513542
TI  - A murine monoclonal anti-idiotype to anti-ribosomal P antibodies: production,
      characterization, and use in systemic lupus erythematosus.
AB  - Overt anti-ribosomal P (anti-P) autoantibodies are restricted to a subset of
      systemic lupus erythematosus (SLE) patients, and are potentially pathogenic.
      Covert anti-P are detected in all other individuals. An idiotype (Id) network is
      nonoperational in those with overt anti-P, whereas it is functional in all
      others. The aim of this study was to produce a murine monoclonal (mAb) anti-Id to
      characterize the anti-P Id network in SLE. BALB/c mice were immunized with
      F(ab')(2) fragments of IgG anti-P from a patient with a broadly cross-reactive
      Id. One mAb was chosen (mAb41) that reacted preferentially to the immunogen. This
      IgG1 mAb bound comparably in ELISAs to affinity-purified anti-P from 11 SLE
      patients with overt anti-P. This binding was partially inhibited with ribosomal P
      antigen. In contrast, it did not bind to affinity-purified control
      autoantibodies, nor to normal human IgG. mAb41 inhibited anti-P binding to
      ribosomal P antigen in immunoassays and on Jurkat cells. No change was detected
      in patients' anti-P antibodies over time when mAb41 was used in Id-specific
      ELISAs. We conclude that mAb41 is an anti-Id that recognizes a public idiotope
      within the antigen-combining site of anti-P antibodies. Thus, it is analogous to
      its human counterparts, and potentially, would modulate the pathogenicity of anti
      P autoantibodies in vivo.

PMID- 11513543
TI  - Analysis of the Ser786Pro interleukin-4 receptor alpha allelic variant in
      allergic and nonallergic asthma and its functional consequences.
AB  - Asthma and other atopic disorders affect a large percentage of the population.
      While many factors contribute to the phenotype of asthma, there is a strong
      genetic predisposition. IL-4 is a central mediator of allergic inflammation.
      Along with IL-13, it is the major cytokine responsible for the induction of IgE
      synthesis. Furthermore, IL-4 acts on Th0 cells and promotes their differentiation
      into Th2 cells resulting in the production of more IL-4 and IL-13, thereby
      propagating the allergic cascade. Both IL-4 and IL-13 utilize IL-4Ralpha as a
      component of their cognate receptor complexes. Eight polymorphisms of the IL
      4Ralpha gene resulting in amino acid changes in the coding sequence have been
      described, and several have been associated with asthma. The central objective of
      this study was to elucidate the role of the Ser786Pro polymorphism in asthma and
      its impact on IL-4R function. One-hundred ninety-six individuals with asthma and
      53 controls were genotyped for Pro786. Pro786 occurred infrequently in the
      general population with an allele frequency of 1.8% and, thus, is unlikely to
      play a major role in atopy or asthma. The Pro786 allele frequency was 1.5% in the
      asthma group and 2.8% in the control group. The asthma group was subdivided into
      allergic and nonallergic asthma, and the Pro786 allele frequencies were 1.7 and
      1.0%, respectively. The data suggested linkage disequilibrium between Ser786Pro
      and the Gln576Arg allele, which is associated with atopy. In order to study the
      impact of the polymorphism on receptor signaling function, we transfected a mouse
      B lymphoma cell line with the wild-type and Pro786 variants of human IL-4Ralpha.
      The Ser786Pro polymorphism in isolation did not affect IL-4R function.

PMID- 11513544
TI  - Preeclampsia, a pregnancy-specific disease, is associated with fetal monocyte
      activation.
AB  - The maternal syndrome of preeclampsia is an exclusively pregnancy-related illness
      involving multiple organs and severe forms may be complicated by HELLP
      (hemolysis, elevated liver enzymes, low platelets) syndrome. Recently, it has
      been proposed that both normal pregnancy and preeclampsia are associated with a
      systemic activation of the nonspecific maternal immune system and that, in
      particular, monocytes have a central role in the adjustment of maternal immune
      functions in pregnancy. Here we have investigated the role of the fetal
      nonadaptive immune system in normal term delivery, uncontrollable preterm labor,
      and preeclampsia. We demonstrate that spontaneous delivery at term as well as
      preterm occurrence of preeclampsia or HELLP syndrome are accompanied by an
      increased intracellular production of IL-6 in fetal monocytes, indicating strong
      activation of this cell type. In contrast, we show that elective cesarean
      delivery at term in the absence of labor or preterm delivery due to
      uncontrollable labor are not accompanied by an increased production of IL-6 in
      these cells. These results suggest that increased IL-6 synthesis in fetal
      monocytes may be a process occurring in association with normal spontaneous term
      delivery and that this process obviously occurs in early pregnancy in case of
      preeclampsia. Therefore, we propose that the activation of fetal monocytes as
      effectors of the innate immunity may be involved in mechanisms inducing
      spontaneous term delivery and that the occurrence of preeclampsia may be based on
      dysfunctions of probably both the maternal and the fetal innate immune system.

PMID- 11513545
TI  - TcR-alpha/beta(+) CD4(-)CD8(-) T cells in humans with the autoimmune
      lymphoproliferative syndrome express a novel CD45 isoform that is analogous to
      murine B220 and represents a marker of altered O-glycan biosynthesis.
AB  - Autoimmune lymphoproliferative syndrome (ALPS), caused by inherited defects in
      apoptosis secondary to mutations in genes encoding Fas/CD95/APO-1 and Fas ligand
      (Fasl)/CD95L, is characterized by nonmalignant lymphadenopathy and splenomegaly,
      increased T cell receptor alpha/beta(+) CD4(-)CD8(-) T cells (alpha/beta(+)
      double-negative T cells [alpha/beta(+)-DNT cells]), autoimmunity,
      hypergammaglobulinemia, and cytokine abnormalities. The alpha/beta(+)-DNT cells
      are immunophenotypically and functionally similar to alpha/beta(+)-DNT cells that
      accumulate in lpr and gld mice, which bear genetic mutations in Fas and FasL. In
      these mice, alpha/beta(+)-DNT cells express the B-cell-specific CD45R isoform
      B220. We show that alpha/beta(+)-DNT cells of ALPS patients, with either Fas or
      FasL mutations, also express B220. In addition, also similar to LPR/gLD mice,
      they have an unusual population of B220-positive CD4(+) T cells. B220 expression,
      together with our finding of characteristic lectin binding profiles, demonstrates
      that cell surface O-linked glycoproteins have undergone specific modifications,
      which may have consequences for lymphocyte trafficking, cell-cell interactions,
      and access to alternative apoptosis pathways.

PMID- 11513546
TI  - Comparative analysis of the morphological, cytochemical, immunophenotypical, and
      functional characteristics of normal human peripheral blood lineage(
      )/CD16(+)/HLA-DR(+)/CD14(-/lo) cells, CD14(+) monocytes, and CD16(-) dendritic
      cells.
AB  - Human peripheral blood (PB) CD14(lo)/HLA-DR(+) cells were initially described as
      a subset of mature monocytes. Recently, it has been suggested that these
      represent a part of a new subset of dendritic cells (DC), characterized by the
      coexpression of MDC-8/HLA-DR/CD16. The aim of the present paper was to analyze
      the morphological, cytochemical, phenotypical, and functional characteristics of
      PB CD16(+)/HLA-DR(+) cells compared to both PB CD14(+) monocytes and CD16(-) DC.
      In contrast to CD14(+) monocytes, purified CD16(+)/HLA-DR(+) cells displayed
      cytoplasmic veils and lacked cytoplasmic myeloperoxidase and alpha-naphthyl
      acetate esterase. Normal human PB CD16(+)/HLA-DR(+) cells also displayed
      phenotypic characteristics different from those of CD14(+) monocytes: they lacked
      the CD64 Fcgamma receptor, showed lower levels of CD32, and expressed higher
      amounts of CD16 compared to CD14(+) monocytes. They also displayed a different
      pattern of expression of other antigens, including CD14, HLA-DR, CD45RA, CD45RO,
      complement receptors and complement regulatory surface proteins, adhesion and
      costimulatory molecules, and cytokine receptors, among others. When compared to
      CD16(-) DC, CD16(+)/HLA-DR(+) cells showed reactivity for CD16, dim positivity
      for CD14, higher expression of both Ig- and complement-receptors and lower
      reactivity for HLA-DR, adhesion, and costimulatory molecules (with the exception
      of CD86). The CD16(+)/HLA-DR(+) cell subset displayed a higher Ig/complement
      mediated phagocytic/oxidative activity than CD16(-) DC, although this activity
      was significantly lower than that of mature monocytes. Regarding cytokine
      production at the single cell level, LPS plus IFN-gamma-stimulated PB CD16(+)/HLA
      DR(+) cells produced significant amounts of IL1beta, IL6, IL12, TNFalpha, and
      IL8; however, the percentage of cytokine-producing cells and the amount of
      cytokine/cell were lower in CD16(+)/HLA-DR(+) cells than in CD14(+) monocytes. In
      addition, upon comparing CD16(+)/HLA-DR(+) cells with CD33(+++)/CD16(-) DC, we
      found that the percentage of cytokine-producing cells and the amount of
      cytokine/cell were significantly different in both cell subsets. In summary, our
      results show that CD16(+)/HLA-DR(+) cells clearly display different morphologic,
      cytochemical, immunophenotypical, and functional characteristics compared to both
      mature monocytes and CD16(-) DC. Interestingly, these cells are more frequent
      than other DC in normal human adult PB and cord blood samples, while they are
      less represented in normal bone marrow.

PMID- 11513547
TI  - Phenotypic comparison of extrathymic human bone-marrow-derived T cells with
      thymic-selected T cells recovered from different tissues.
AB  - We have previously described extrathymic generation of human T cells from
      purified stem cells in the bone marrow of athymic immune deficient mice. This
      system provides a pure population of extrathymic human T cells that is devoid of
      contamination by peripheral expansion of thymic-selected T cells. In the current
      studies, we phenotypically compared the extrathymic human T cells (Ex-T) to T
      cells from human peripheral blood leukocytes (PBL), umbilical cord blood (CB),
      bone marrow (BM), and postnatal thymus. There were few CD4(+)/CD8(+) double
      positive (DP) cells in PBL, CB, BM, and Ex-T, in comparison with over 85% DP
      cells in thymus. More CD8(+) and CD4(dim) cells were observed in Ex-T than in the
      thymic-selected cells. Ex-T and T cells in thymus and peripheral tissues differed
      in their CD8 isoforms. There were more TCRgamma/delta T cells in PBL, CB, BM, and
      Ex-T than in thymus. Similar to the bright CD3(+) T cells in thymus, T cells in
      PBL, CB, and BM were CD3 bright and expressed the adhesion molecules CD44 and L
      selectin (CD62L), while intermediate CD3 T cells in thymus lacked CD44 and L
      selectin. However, the majority of Ex-T only expressed CD44 but not L-selectin.
      In summary, thymic- and extrathymic-derived T cells are phenotypically different.
      The identification of extrathymically derived T cells in humans will allow us to
      begin to understand their role in the early contribution to immune recovery
      posttransplantation and their possible involvement in autoimmunity and other
      disease states.

PMID- 11513548
TI  - Do T helpers 1 and 2 recognize different class II MHC molecules? Humoral and
      cellular immune responses to soluble allergen from Aspergillus fumigatus Asp f2.
AB  - Cellular signals leading to T helper (Th)1/Th2 shift are not well known. Here we
      demonstrate that Th1 possibly recognizes peptides presented by the IE molecule of
      MHC class II while Th2 is activated by the recognition of peptides presented by
      the IA molecule. BALB/c mice immunized with Asp f2 developed stable IA-restricted
      Th2 immune response to the 12th day after immunization, as analyzed by IL-2
      production. On the contrary, early Th0 cells did not secrete IL-2 upon Asp f2
      stimulation but did produce a high level of IL-2 if stimulated in the presence of
      anti-IA Abs. This effect of anti-IA Abs on early Th0 cells was both MHC IE and
      CD4(+) cell restricted. In vivo blocking of Asp f2 peptide presentation by the IA
      molecule led to the formation of antigen-specific cytotoxicity as demonstrated
      using immune splenocytes as effector cells and Asp f2 loaded P815 cells as
      targets.

PMID- 11513549
TI  - Infection of human B lymphocytes with MMR vaccine induces IgE class switching.
AB  - Circulating immunoglobulin E (IgE) is one of the characteristics of human
      allergic diseases including allergic asthma. We recently showed that infection of
      human B cells with rhinovirus or measles virus could lead to the initial steps of
      IgE class switching. Since many viral vaccines are live viruses, we speculated
      that live virus vaccines may also induce IgE class switching in human B cells. To
      examine this possibility, we selected the commonly used live attenuated measles
      mumps rubella (MMR) vaccine. Here, we show that infection of a human IgM(+) B
      cell line with MMR resulted in the expression of germline epsilon transcript. In
      addition, infection of freshly prepared human PBLs with this vaccine resulted in
      the expression of mature IgE mRNA transcript. Our data suggest that a potential
      side effect of vaccination with live attenuated viruses may be an increase in the
      expression of IgE.

PMID- 11513550
TI  - Relationship between complement activation and renal deposition of immune
      complexes made with IgG2a monoclonal antibodies.
AB  - Previous studies identified a single murine monoclonal IgG2a anti-dinitrophenyl
      antibody that, when combined with the antigen, formed immune complexes (IC) that
      were preferentially deposited in glomeruli. The present study examined the
      clearance and organ localization in Balb/c mice of expanded panels of
      radiolabeled IC containing murine monoclonal antibodies. The results identified a
      second IgG2a antibody that formed IC with a predilection for renal deposition. IC
      made with the two IgG2a antibodies that were preferentially deposited in the
      kidney were the least efficient binders of human C1q or homologous murine C3b and
      C4b within the IgG2a panel. These observations suggest a new model of IC-mediated
      renal disease initiation in which relatively weak complement activation leads to
      inefficient IC clearance by complement receptor-bearing circulating cells and
      consequent IC deposition in tissues susceptible to IC-mediated injury.

PMID- 11513551
TI  - NZM2328: a new mouse model of systemic lupus erythematosus with unique genetic
      susceptibility loci.
AB  - Among NZB/W-derived New Zealand mixed (NZM) strains, only NZM/Aeg2410 (NZM2410)
      has been well characterized. In contrast to NZM2410, NZM2328 mice develop
      autoantibodies and acute and severe chronic glomerulonephritis (GN) with female
      predominance similarly to NZB/WF1 and humans with systemic lupus erythematosus
      (SLE). Chronic GN with glomerular sclerosis and tubular atrophy but not acute GN
      was correlated with severe proteinuria. In a backcross analysis of (NZM2328 X
      C57L/J) F1 X NZM2328, four SLE susceptibility genomic intervals were identified.
      One of them (Cgnz1) is on the telomeric end of chromosome 1 and close to Sle1. It
      was significantly linked to chronic GN. A locus (Agnz1) distinct from Cgnz1 on
      this interval was suggestively linked to acute GN. Two genetic intervals on
      chromosome 17 were also suggestively linked to acute GN, one of which is the H-2
      Tnf complex, while the other (Agnz2) is on the distal end of the chromosome. A
      single locus (Adaz1) identified in the midregion of chromosome 4 in NZM2328 mice
      was suggestively linked to plasma levels of IgG anti-dsDNA autoantibodies. These
      results differ significantly from those in the backcross analysis of (NZM2410 X
      C57BL/6)F1 X NZM2410 by other investigators. They support the concept that
      different sets of genes are involved in acute and chronic GN. The genomic
      differences between the NZM strains and between C57L/J and C57BL/6 account for
      the differences between our analysis and that on NZM 2410. These results provide
      evidence for the importance of background genes on the expression of SLE, with
      implications for genetic studies of human SLE.

PMID- 11513552
TI  - A fluorescent reverse transcription-polymerase chain reaction assay to quantify
      the lipoprotein lipase messenger RNA.
AB  - Relative quantitative reverse transcription-polymerase chain reaction (rqRT-PCR),
      which allows an accurate quantification of the amount of mRNA in samples
      potentially differing in the quality of their RNA preparation, was used to
      quantify lipoprotein lipase (LPL) mRNA in ovine adipose tissue. A comparative
      evaluation of four rqRT-PCR procedures was carried out. The amount of LPL mRNA
      was assayed relative to either that of gamma-actin (ACT) or cyclophilin (CYC)
      mRNA, used as endogenous standard. Independent (INACT and INCYC procedures) or
      simultaneous (COACT and COCYC procedures) amplifications have been compared.
      Fluorescently labelled primers yielded PCR products which were quantitatively
      analysed using an automated DNA sequencer. After optimizing the PCR cycle number
      and verifying that the amounts of ACT and CYC mRNA varied only weakly according
      to the nutritional conditions studied, we have tested the ability of the four
      procedures to quantify specific variations in LPL mRNA. The repeatability of each
      step and the overall assay reproducibility were also examined. The COACT and
      INCYC procedures were finally retained to accurately quantify LPL mRNA in AT from
      nine underfed or refed ewes, and gave highly correlated results (r=0.98, p<0.01).
      In addition, significant correlations (r=0.83, p<0.01 and r=0.92, p<0.01 for
      COACT and INCYC, respectively) were observed with the LPL activity in AT.

PMID- 11513553
TI  - Detection and typing of TT virus DNA genotype by the PCR-RFLP method.
AB  - TT virus (TTV) is a novel single-stranded DNA virus that was identified in
      patients with post-transfusion-hepatitis of non-A-G type in Japan in 1997. We
      developed a new detection and typing method for TTV DNA strains, by combining
      polymerase chain reaction (PCR) and restriction fragment length polymorphism (PCR
      RFLP) techniques. TTV DNA was amplified by nested-PCR with TTV-specific mixed
      primers derived from the conserved open reading frame 1 (ORF1) region of the
      published TTV DNA sequences. Using the enzymes Hae III, Dra I, Eco RI and Pst I,
      we were able to distinguish between the four TTV genotypes. In 200 serum samples
      obtained from healthy pregnant women at an outpatient clinic, the positive rate
      of TTV detection was 27.0%, almost identical to the positive rate of the
      detection of ORF1-PCR in Japanese healthy individuals. The strains detected in
      the positive serum samples were genotype 1a (9.3%), genotype 1b (11.1%), genotype
      2 (51.9%), genotype 3 (7.4%) and other genotypes (1.9%). This results indicate
      that genotype 1 and genotype 2 were the two major strains in the Japanese
      population. Moreover, 10 serum samples (18.5%) presented RFLP patterns in which
      some genotypes were mixed.

PMID- 11513554
TI  - Detection of Plasmodium falciparum and Wuchereria bancrofti infected blood
      samples using multiplex PCR.
AB  - A rapid and sensitive multiplex PCR has been developed for the diagnosis of
      multiple parasitic infection in human blood. Infection is detected by a single
      multiplex PCR reaction containing two pairs of oligonucleotide primers whereby
      each primer is specific for each parasite species. These primer sets amplified
      400 and 450-bp fragments for Wuchereria bancrofti and 208-bp fragment for
      Plasmodium falciparum. The PCR products derived from each parasite species were
      visualized in ethidium bromide-stained agarose gels, therefore allowing the rapid
      identification of any, or all, of the two human parasites, if present, in a
      single amplification reaction. This multiplex PCR was very sensitive with the
      ability to detect the presence of as little as 10 pg of parasite DNA. The primers
      used in this multiplex PCR also showed highly specific amplification of each
      respective parasite DNA without the presence of non-specific and non-target PCR
      products. This multiplex PCR system was used to analyse 36 human blood samples of
      Myanmar workers in the endemic area at Tak Province, Thailand. Two samples showed
      the multiple infection, 27 samples were either infected with W. bancrofti or P.
      falciparum and seven samples were negative for both methods. The high
      sensitivity, specificity and rapidity of this multiplex PCR method make it
      suitable for large-scale epidemiological studies and following of drug treatment.

PMID- 11513555
TI  - Multiplex PCR for the detection of tetracycline resistant genes.
AB  - Specific primer pairs were selected for the PCR amplification of 14 tetracycline
      resistant genes commonly found in Gram positive and Gram negative organisms.
      Combinations of primer pairs were used in multiplex PCR reactions to detect
      specific groups of tet genes as follows; Group I tet (B), tet (C), tet (D); Group
      II tet (A), tet (E), tet (G); Group III tet (K), tet (L), tet (M), tet (O), tet
      (S); Group IV tetA (P), tet (Q), tet (X). To test the multiplex PCR, Groups I and
      II were used on 25 clinical isolates of Salmonella enterica serovar Typhimurium
      DT104. Group III primers were used to investigate 19 clinical isolates of
      methicillin-resistant Staphylococcus aureus. Multiplex PCR should result in
      significant savings in terms of labour and cost in analysis of a large number of
      strains when compared with using an individual PCR for targeting each gene. It
      may also be a useful method to differentiate the types of tetracycline resistance
      when used as an additional marker for the purpose of outbreak investigation and
      surveillance.

PMID- 11513556
TI  - Single nucleotide polymorphisms of the protoporphyrinogen oxidase gene: inter
      population heterogeneity of allelic variation.
AB  - Five single nucleotide polymorphisms (SNPs) in the protoporphyrinogen oxidase
      gene (PPOX) were used for inter-population comparisons of six South African
      populations and two non-South African Caucasian populations. Novel polymorphisms
      identified in the promoter region and exon 11 of the PPOX gene, as well as three
      known variants in exon 1 and intron 2, were analysed using single-strand
      conformation polymorphism (SSCP) and restriction enzyme analyses. Significant
      population differences were found for four of the five polymorphisms analysed. A
      G-to-A transition was found at nucleotide position -1081 and is the first
      polymorphism to be identified in the 5' promoter region of the gene. A novel A-to
      C substitution at nucleotide position 3880 in exon 11 was not detected in
      subjects of European descent. This study represents the first inter-population
      comparison of allelic variation at the PPOX locus. The significant differences
      observed between populations demonstrate the importance of population
      considerations when marker association studies are performed at this locus.

PMID- 11513557
TI  - Polymorphism screening of the insulin receptor-related receptor gene (INSRR) on
      1q in Pima Indians.
AB  - INSRR coding for the insulin receptor-related receptor (IRR) is located within
      the 1q21-q23 region linked with type-2 diabetes mellitus in Pima Indians and
      Caucasians. Although the ligand and biological function of this receptor are not
      yet known, its tyrosine kinase phosphorylates proteins involved in insulin
      signaling, and IRR may also play a role in the control of the insulin producing
      beta-cell mass. Therefore, defects in INSRR could contribute to susceptibility to
      type-2 diabetes. By screening the 22 exons, 5' and 3' flanking sequences, and
      most introns in 20 Pima Indians and one Caucasian control, we detected nine
      diallelic variants, including eight single nucleotide polymorphisms (SNPs), and a
      length polymorphism involving a 26-nt motif. In this study sample, four of the
      identified SNPs were rare, while the remaining five common variants located
      within 4.5 kb from the 3' end of the gene were in linkage disequilibrium. When
      analysed in selected diabetic and non-diabetic Pimas, none of the markers was
      associated with the disease. We conclude that INSRR has no detectable mutations
      contributing to diabetes in the Pima Indians. However, information on the novel
      markers may prove useful for association studies of this candidate gene in other
      populations.

PMID- 11513558
TI  - Variation of the sequence in the gene encoding for transmembrane protein M of
      canine coronavirus (CCV).
AB  - A nucleotide variability in the sequence of the gene encoding for the
      transmembrane protein M of canine coronavirus (CCV) is described. A total of 177
      faecal samples from pups with enteritis were analysed by a PCR and n-PCR specific
      for CCV. Four samples, collected from a dog presenting a long-duration shedding
      of CCV, and a sample from another diarrhoeic dog, were found positive by PCR but
      negative by n-PCR. Sequence analysis of the samples revealed silent nucleotide
      substitutions in the binding site of the internal primer used for the n-PCR.
      Moreover, the nucleotide substitutions occurring over the whole fragment of the
      five samples analysed were similar.

PMID- 11513559
TI  - A polymorphic marker for the human cathepsin B gene.
AB  - Human cathepsin B (CTSB) is a proteolytic enzyme implicated in tumor invasion and
      metastasis. We describe a PCR-based polymorphic marker for this gene comprising
      two amplimers differing in length by 19 consecutive nucleotides in intron 7, near
      the exon 8 splice acceptor site, identifying two gene alleles (A and B). Allele
      frequencies were 0.614 for A and 0.386 for the B allele, with an observed
      heterozygosity of 0.457 in a cohort of 70 non-related Australian blood donors.
      One additional nucleotide difference was also revealed through sequencing. The
      human CTSB gene is located on chromosome 8 and the alleles described here can
      potentially be used as markers in linkage and association studies of cancers and
      other diseases.

PMID- 11513562
TI  - Solitary cancer cells as a possible source of tumour dormancy?
AB  - Metastasis can occur many years after primary tumour treatment. However, the
      status of the tumour during this period of dormancy is poorly understood. As part
      of our ongoing experimental studies on mechanisms of metastasis, we have
      discovered that large numbers of disseminated single cells may persist in
      secondary sites for extended time periods. Identification of these cells was
      facilitated by in vivo techniques developed to quantify the fate of individual
      cells during the metastatic process. Here we review these in vivo techniques and
      findings. We also discuss the potential clinical implications if dormant solitary
      cells exist in appreciable numbers in cancer patients.

PMID- 11513560
TI  - GT repeat polymorphism in the 5' flanking region of the human growth hormone
      receptor gene.
AB  - A polymorphic GT dinucleotide repeat sequence has been identified in the 5'
      flanking region of the human growth hormone receptor (hGHR) gene on chromosome
      5p13.1-p12, within the promoter region of the V9 5'UTR exon. Thirteen alleles
      have been identified in 50 non-related individuals, with an observed
      heterozygosity of 52%. The major allele contains 24 repeats, although a range of
      19-32 repeats has been observed. Codominant segregation was demonstrated in five
      two-generation and two three-generation families. This marker may be useful in
      analysing the role of the hGHR gene in pre- and postnatal growth disorders.

PMID- 11513563
TI  - Dormancy in a model of murine B cell lymphoma.
AB  - A B cell lymphoma model of dormancy in mice was established by prior immunization
      to the B cell membrane immunoglobulin idiotype. The antibody to the idiotype was
      the major factor in inducing and maintaining dormancy and acted primarily as an
      agonist rather than via effector functions. CD8+ T cells synergized with anti-Id
      in inducing dormancy by secreting IFN-gamma. Cycling in the dormant population
      was reduced 3-5 fold, but each mouse contained approximately 10(6) tumor cells in
      its spleen, some of which were cycling, during the 1.5 years of observation.
      Thus, replication is balanced by cell death.

PMID- 11513564
TI  - T-cell immunity in the induction and maintenance of a tumour dormant state.
AB  - We conclude from animal tumour model studies that T cell immunity can play an
      essential role in the induction and maintenance of tumour dormancy. Evidence was
      found in tumour dormancy situations for active control of proliferating tumour
      cells by CD8 memory T cells leading to a long-term balance in the bone marrow
      between low numbers of tumour cells and immunological memory. In breast cancer
      patients, too, the bone marrow may represent a privileged compartment for tumour
      dormancy and immunological memory. Upon restimulation with tumour antigen pulsed
      autologous dendritic cells, bone marrow-derived memory T cells from cancer
      patients could be shown to exist and to become activated into potent anti-tumour
      effector cells.

PMID- 11513565
TI  - Tumour dormancy: findings and hypotheses from clinical research on breast cancer.
AB  - Breast cancer metastatic development is commonly considered as resulting from
      continuous tumour growth from tumour seeding until clinical recurrence is
      documented. Continuous growth model inferences, however, fail to explain clinical
      findings concerning local recurrences, as well as the time-distribution of first
      treatment failure and mortality for patients undergoing mastectomy. The tumour
      dormancy hypothesis is considered to provide a more reasonable description of the
      natural history of breast cancer, while primary tumour removal is believed to be
      a potential perturbing factor for metastasis development. A new model of the
      natural history of operable breast cancer, incorporating tumour dormancy and
      starting signals from surgery for micrometastatic growth is proposed.

PMID- 11513566
TI  - Early cancer cell dissemination and late metastatic relapse: clinical reflections
      and biological approaches to the dormancy problem in patients.
AB  - Two clinical entities, unknown-primary cancer and inadvertent transmission of
      cancer with organ transplants are reviewed and discussed in the context of early
      and occult tumor cell dissemination. Both entities are taken as chief witnesses
      for cell dissemination being an early event in tumor progression. The involuntary
      transmission of tumor by organ grafts directly supports the notion that very few
      quiescent cells lodging at improbable sites such as kidney or heart suffice to
      generate de novo metastatic disease in the organ recipient. As to the nature of
      the cells and their biological and clinical significance a short review is given
      on the detection of disseminated cells in bone marrow and their prognostic
      significance for a metastatic relapse in patients with resected primary tumors. A
      novel single-cell genomic analysis is described, that allows the detection of
      multiple chromosomal aberration in single tumor cells.

PMID- 11513567
TI  - Molecular evolution of chronic myeloid leukaemia.
AB  - Chronic myeloid leukaemia (CML) is a clonal disorder of the pluripotent
      haematopoietic stem cell. The typical triphasic course of CML starts with the
      premalignant chronic phase initiated by BCR-ABL hybrid oncogene formation.
      Secondary genetic and epigenetic aberrations accompany the progression to the
      accelerated phase and fatal blastic crisis. Properly timed bone marrow
      transplantation in eligible patients can result in durable remissions or cure.
      Both of these states are often accompanied by a long-term persistence of
      quiescent leukaemic cells. Accordingly, a "functional cure" (i.e. tumour dormancy
      induction), rather than complete eradication of the malignant cells, is an
      adequate therapeutical goal. The level of the residual BCR-ABL-positive clones
      should be monitored and salvage treatment initiated whenever these quiescent
      leukaemic cells exit their dormant state.

PMID- 11513568
TI  - Stereoselective total synthesis of axially chiral natural products via biaryl
      lactones.
AB  - Axially chiral natural products are rewarding synthetic targets, due to their
      wide distribution, diverse structures, and promising bioactivities. The "lactone
      concept" provides an efficient strategy for the regio- and stereoselective
      construction of even bulky biaryls. Key steps are the intramolecular coupling of
      the ester-prefixed molecular portions to give (mostly configurationally unstable)
      biaryl lactones and their stereoselective ring cleavage (usually by dynamic
      kinetic resolution), leading to the one or-optionally-the other atropisomeric
      product from the same lactone. Stereoisomeric byproducts can be recycled by
      recyclization back to the lactone. The broad applicability of the method is
      demonstrated in the total synthesis of selected representatives from five very
      different classes of natural biaryl products.

PMID- 11513569
TI  - Competitive pathways via nonadiabatic transitions in photodissociation.
AB  - Photodissociation processes of molecules and radicals involving multiple pathways
      and nonadiabatic crossings are studied using the photofragment imaging technique
      and the core-sampling version of time-of-flight spectroscopy. Capabilities and
      challenges are illustrated by two systems. The isocyanic acid system demonstrates
      how interactions among potential energy surfaces can change during dissociation.
      The hydroxymethyl photodecomposition system highlights Rydberg-valence
      interactions common in free radicals. The cross-fertilization between theory and
      experiment is emphasized.

PMID- 11513570
TI  - Catalytic functionalization of arenes and alkanes via C-H bond activation.
AB  - Several novel synthetic reactions of arenes and alkanes discovered and
      investigated in our laboratory are summarized here. These include olefin
      arylation, hydroarylation of alkynes, hydroxylation of arenes, carboxylation of
      arenes and alkanes, and aminomethylation and acetoxylation of alkanes. Most of
      these reactions are catalyzed by highly electrophilic transition metal cationic
      species generated in situ in an acid medium, involving electrophilic metalation
      of C-H bonds of arenes and alkanes which lead to the formation of aryl-metal and
      alkyl-metal sigma-complexes.

PMID- 11513571
TI  - 1,1-Dimetallic reagents for the elaboration of stereoselectively di- or
      trisubstituted linear substrates.
AB  - Although gem-dimetallic species have been known for a long time, and reacted once
      or twice with electrophiles, the allyl zincation of substituted vinyl metals has
      emerged as a particularly efficient access to such species. This is due to a high
      face selectivity, in the addition to the C=C bond, which can be governed by
      vicinal or more remote heteroatoms. This strategy has some aspects in common with
      the well-known allylations or aldol condensations to carbonyl derivatives. But in
      the present case, the C=C bond has a low polarity. We present here some examples
      which lead to di- or polysubstituted linear substrates, of given geometry, where
      the organodimetallic obtained has been doubly protonated by water. Further
      elaborations (to alkenes, ketones, etc.) are possible.

PMID- 11513572
TI  - Mass-independent isotopic compositions in terrestrial and extraterrestrial solids
      and their applications.
AB  - In 1983, Thiemens and Heidenreich reported the first chemically produced mass
      independent isotope effect. This work has been shown to have a wide range of
      applications, including atmospheric chemistry, solar system evolution, and
      chemical physics. This work has recently been reviewed (Weston, R. E. Chem. Rev.
      1999, 99, 2115-2136; Thiemens, M. H. Science 1999, 283, 341-345). In this
      Account, observations of mass-independent isotopic compositions in terrestrial
      and Martian solids are reviewed. A wide range of applications, including
      formation and transport of aerosols in the present atmosphere, chemistry of
      ancient atmospheres and oceans, history and coupling of the atmosphere-surface in
      the Antarctic dry valleys, origin and evolution of oxygen in the Earth's earliest
      environment, and the chemistry of the atmosphere and surface of Mars, are
      discussed.

PMID- 11513574
TI  - Hexafluorobenzene photochemistry: wellspring of fluorocarbon structures.
AB  - Ultraviolet irradiation of hexafluorobenzene in the vapor phase gives exclusively
      its Dewar valence isomer, from which a wealth of highly fluorinated compounds has
      been derived. Photoexcited in solution, hexafluorobenzene is capable of
      cycloaddition with a variety of unsaturated molecules. Like the Dewar benzene,
      resulting adducts have served as intermediates en route to many new fluorocarbons
      and fluorocarbon derivatives.

PMID- 11513573
TI  - The gas-phase chemistry of cyclodextrin inclusion complexes.
AB  - Complexes of cyclodextrins with amino acid analytes are produced in the gas phase
      and are ideal for the study of molecular recognition. In this Account, we discuss
      the evidence for the presence of gas-phase inclusion complexes and the nature of
      the interaction. The use of cyclodextrins as chiral selectors in gas-phase guest
      exchange reactions is illustrated, and the nature of the enantioselectivity is
      discussed. The development of the enantioselective reaction into an analytical
      method for determining enantiomeric excess is also described.

PMID- 11513575
TI  - Chiral studies across the spectrum of polymer science.
AB  - This Account describes how stereochemical ideas focused on chirality have been
      directed widely across polymer science allowing experiments that could not be
      conducted on small molecules and leading to new insights and new kinds of
      materials. In one approach, a helical polymer was studied, and it was discovered
      how the chiral information necessary to choose helical sense is greatly
      amplified. In another approach, the racemization kinetics of atropisomers were
      used to characterize the restrictions to motion associated with a polyelectrolyte
      that forms clusters around hydrophobic groups in water and in an entirely
      different system, the glassy state formed by polymers.

PMID- 11513576
TI  - Cobalamin-dependent methyltransferases.
AB  - Cobalamin cofactors play critical roles in radical-catalyzed rearrangements and
      in methyl transfers. This Account focuses on the role of methylcobalamin and its
      structural homologues, the methylcorrinoids, as intermediaries in methyl transfer
      reactions, and particularly on the reaction catalyzed by cobalamin-dependent
      methionine synthase. In these methyl transfer reactions, the cobalt(I) form of
      the cofactor serves as the methyl acceptor. Biological methyl donors to cobalamin
      include N5-methyltetrahydrofolate, other methylamines, methanol, aromatic methyl
      ethers, acetate, and dimethyl sulfide. The challenge for chemists is to determine
      the enzymatic mechanisms for activation of these unreactive methyl donors and to
      mimic these amazing biological reactions.

PMID- 11513577
TI  - Subsite specificity of memapsin 2 (beta-secretase): implications for inhibitor
      design.
AB  - Memapsin 2 is the protease known as beta-secretase whose action on beta-amyloid
      precursor protein leads to the production of the beta-amyloid (Abeta) peptide.
      Since the accumulation of Abeta in the brain is a key event in the pathogenesis
      of Alzheimer's disease, memapsin 2 is an important target for the design of
      inhibitory drugs. Here we describe the residue preference for the subsites of
      memapsin 2. The relative k(cat)/K(M) values of residues in each of the eight
      subsites were determined by the relative initial cleavage rates of substrate
      mixtures as quantified by MALDI-TOF mass spectrometry. We found that each subsite
      can accommodate multiple residues. The S(1) subsite is the most stringent,
      preferring residues in the order of Leu > Phe > Met > Tyr. The preferences of
      other subsites are the following: S(2), Asp > Asn > Met; S(3), Ile > Val > Leu;
      S(4), Glu > Gln > Asp; S(1)', Met > Glu > Gln > Ala; S(2)', Val > Ile > Ala;
      S(3)', Leu > Trp > Ala; S(4)', Asp > Glu > Trp. In general, S subsites are more
      specific than the S' subsites. A peptide comprising the eight most favored
      residues (Glu-Ile-Asp-Leu-Met-Val-Leu-Asp) was found to be hydrolyzed with the
      highest k(cat)/K(M) value so far observed for memapsin 2. Residue preferences at
      four subsites were also studied by binding of memapsin 2 to a combinatorial
      inhibitor library. From 10 tight binding inhibitors, the consensus preferences
      were as follows: S(2), Asp and Glu; S(3), Leu and Ile; S(2)', Val; and S(3)', Glu
      and Gln. An inhibitor, OM00-3, Glu-Leu-Asp-LeuAla-Val-Glu-Phe (where the asterisk
      represents the hydroxyethylene tansition-state isostere), designed from the
      consensus residues, was found to be the most potent inhibitor of memapsin 2 so
      far reported (K(i) of 3.1 x 10(-10) M). A molecular model of OM00-3 binding to
      memapsin 2 revealed critical improvement of the interactions between inhibitor
      side chains with enzyme over a previous inhibitor, OM99-2 [Ghosh, A. K., et al.
      (2000) J. Am. Chem. Soc. 14, 3522-3523].

PMID- 11513578
TI  - Crystal structure of the Rac1-RhoGDI complex involved in nadph oxidase
      activation.
AB  - A heterodimer of prenylated Rac1 and Rho GDP dissociation inhibitor was purified
      and found to be competent in NADPH oxidase activation. Small angle neutron
      scattering experiments confirmed a 1:1 stoichiometry. The crystal structure of
      the Rac1-RhoGDI complex was determined at 2.7 A resolution. In this complex in
      which Rac1 is bound to GDP, the switch I region of Rac1 is in the GDP
      conformation whereas the switch II region resembles that of a GTP-bound GTPase.
      Two types of interaction between RhoGTPases and RhoGDI were investigated. The
      lipid-protein interaction between the geranylgeranyl moiety of Rac1 and RhoGDI
      resulted in numerous structural changes in the core of RhoGDI. The interactions
      between Rac1 and RhoGDI occur through hydrogen bonds which involve a number of
      residues of Rac1, namely, Tyr64(Rac), Arg66(Rac), His103(Rac), and His104(Rac),
      conserved within the Rho family and localized in the switch II region or in its
      close neighborhood. Moreover, in the switch II region of Rac1, hydrophobic
      interactions involving Leu67(Rac) and Leu70(Rac) contribute to the stability of
      the Rac1-RhoGDI complex. Inhibition of the GDP-GTP exchange in Rac1 upon binding
      to RhoGDI partly results from interaction of Thr35(Rac) with Asp45(GDI). In the
      Rac1-RhoGDI complex, the accessibility of the effector loops of Rac1 probably
      accounts for the ability of the Rac1-RhoGDI complex to activate the NADPH
      oxidase.

PMID- 11513579
TI  - Mechanism of NADPH oxidase activation by the Rac/Rho-GDI complex.
AB  - The low molecular weight GTP binding protein Rac is essential to the activation
      of the NADPH oxidase complex, involved in pathogen killing during phagocytosis.
      In resting cells, Rac exists as a heterodimeric complex with Rho GDP dissociation
      inhibitor (Rho-GDI). Two types of interactions exist between Rac and Rho-GDI: a
      protein-lipid interaction, implicating the polyisoprene of the GTPase, as well as
      protein-protein interactions. Using the two-hybrid system, we show that
      nonprenylated Rac1 interacts very weakly with Rho-GDI, pointing to the
      predominant role of protein-isoprene interaction in complex formation. In the
      absence of this strong interaction, we demonstrate that three sites of protein
      protein interaction, Arg66(Rac)-Leu67(Rac), His103(Rac), and the C-terminal
      polybasic region Arg183(Rac)-Lys188(Rac), are involved and cooperate in complex
      formation. When Rac1 mutants are prenylated by expression in insect cells, they
      all interact with Rho-GDI. Rho-GDI is able to exert an inhibitory effect on the
      GDP/GTP exchange reaction except in the complex in which Rac1 has a deletion of
      the polybasic region (Arg183(Rac)-Lys188(Rac)). This complex is, most likely,
      held together through protein-lipid interaction only. Although able to function
      as GTPases, the mutants of Rac1 that failed to interact with Rho-GDI also failed
      to activate the NADPH oxidase in a cell-free assay after loading with GTP. Mutant
      Leu119(Rac)Gln could both interact with Rho-GDI and activate the NADPH oxidase.
      The Rac1/Rho-GDI and Rac1(Leu119Gln)/Rho-GDI complexes, in which the GTPases were
      bound to GDP, were found to activate the oxidase efficiently. These data suggest
      that Rho-GDI stabilizes Rac in an active conformation, even in the GDP-bound
      state, and presents it to its effector, the p67phox component of the NADPH
      oxidase.

PMID- 11513580
TI  - Locating monovalent cations in the grooves of B-DNA.
AB  - Here we demonstrate that monovalent cations can localize around B-DNA in
      geometrically regular, sequence-specific sites in oligonucleotide crystals.
      Positions of monovalent ions were determined from high-resolution X-ray
      diffraction of DNA crystals grown in the presence of thallium(I) cations (Tl(+)).
      Tl(+) has previously been shown to be a useful K(+) mimic. Tl(+) positions
      determined by refinement of model to data are consistent with positions
      determined using isomorphous F(Tl) - F(K) difference Fouriers and anomalous
      difference Fouriers. None of the observed Tl(+) sites surrounding CGCGAATTCGCG
      are fully occupied by Tl(+) ions. The most highly occupied sites, located within
      the G-tract major groove, have estimated occupancies ranging from 20% to 35%. The
      occupancies of the minor groove sites are estimated to be around 10%. The Tl(+)
      positions in general are not in direct proximity to phosphate groups. The A-tract
      major groove appears devoid of localized cations. The majority of the observed
      Tl(+) ions interact with a single duplex and so are not engaged in lattice
      interactions or crystal packing. The locations of the cation sites are dictated
      by coordination geometry, electronegative potential, avoidance of electropositive
      amino groups, and cation-pi interactions. It appears that partially dehydrated
      monovalent cations, hydrated divalent cations, and polyamines compete for a
      common binding region on the floor of the G-tract major groove.

PMID- 11513581
TI  - Amphoterin includes a sequence motif which is homologous to the Alzheimer's beta
      amyloid peptide (Abeta), forms amyloid fibrils in vitro, and binds avidly to
      Abeta.
AB  - Many of the proteins associated with amyloidoses have been found to share
      structural and sequence similarities, which are believed to be responsible for
      their capability to form amyloid fibrils. Interestingly, some proteins seem to be
      able to form amyloid-like fibrils although they are not associated with
      amyloidoses. This indicates that the ability to form amyloid fibrils may be a
      general property of a greater number of proteins not associated with these
      diseases. In the present work, we have searched for amyloidogenic consensus
      sequences in two current protein/peptide databases and show that many proteins
      share structures which can be predicted to form amyloid. One of these potentially
      amyloidogenic proteins is amphoterin (also known as HMG-1), involved in neuronal
      development and a ligand for the receptor for advanced glycation end products
      (RAGE). It contains an amyloidogenic peptide fragment which is highly homologous
      to the Alzheimer's amyloid beta-peptide. If enzymatically released from the
      native protein, it forms amyloid-like fibrils which are visible in electron
      microscopy, exhibit apple green birefringence under polarized light after Congo
      red staining, and increases thioflavin T fluorescence. This fragment also shows
      high affinity to Abeta as a free peptide or while part of the native protein. Our
      results support the hypothesis that the potential to form amyloid is a common
      characteristic of a number of proteins, independent of their relation to
      amyloidoses, and that this potential can be predicted based on the
      physicochemical properties of these proteins.

PMID- 11513582
TI  - Crystal structure of thrombin-ecotin reveals conformational changes and extended
      interactions.
AB  - The protease inhibitor ecotin fails to inhibit thrombin despite its broad
      specificity against serine proteases. A point mutation (M84R) in ecotin results
      in a 1.5 nM affinity for thrombin, 10(4) times stronger than that of wild-type
      ecotin. The crystal structure of bovine thrombin is determined in complex with
      ecotin M84R mutant at 2.5 A resolution. Surface loops surrounding the active site
      cleft of thrombin have undergone significant structural changes to permit
      inhibitor binding. Particularly, the insertion loops at residues 60 and 148 in
      thrombin, which likely mediate the interactions with macromolecules, are
      displaced when the complex forms. Thrombin and ecotin M84R interact in two
      distinct surfaces. The loop at residue 99 and the C-terminus of thrombin contact
      ecotin through mixed polar and nonpolar interactions. The active site of thrombin
      is filled with eight consecutive amino acids of ecotin and demonstrates
      thrombin's preference for specific features that are compatible with the thrombin
      cleavage site: negatively charged-Pro-Val-X-Pro-Arg-hydrophobic-positively
      charged (P1 Arg is in bold letters). The preference for a Val at P4 is clearly
      defined. The insertion at residue 60 may further affect substrate binding by
      moving its adjacent loops that are part of the substrate recognition sites.

PMID- 11513583
TI  - Polar residues in the protein core of Escherichia coli thioredoxin are important
      for fold specificity.
AB  - Most globular proteins contain a core of hydrophobic residues that are
      inaccessible to solvent in the folded state. In general, polar residues in the
      core are thermodynamically unfavorable except when they are able to form
      intramolecular hydrogen bonds. Compared to hydrophobic interactions, polar
      interactions are more directional in character and may aid in fold specificity.
      In a survey of 263 globular protein structures, we found a strong positive
      correlation between the number of polar residues at core positions and protein
      size. To probe the importance of buried polar residues, we experimentally tested
      the effects of hydrophobic mutations at the five polar core residues in
      Escherichia coli thioredoxin. Proteins with single hydrophobic mutations (D26I,
      C32A, C35A, T66L, and T77V) all have cooperative unfolding transitions like the
      wild type (wt), as determined by chemical denaturation. Relative to wt, D26I is
      more stable while the other point mutants are less stable. The combined 5-fold
      mutant protein (IAALV) is less stable than wt and has an unfolding transition
      that is substantially less cooperative than that of wt. NMR spectra as well as
      amide deuterium exchange indicate that IAALV is likely sampling a number of low
      energy structures in the folded state, suggesting that polar residues in the core
      are important for specifying a well-folded native structure.

PMID- 11513584
TI  - Evolution of enzymatic activities in the enolase superfamily: identification of
      the general acid catalyst in the active site of D-glucarate dehydratase from
      Escherichia coli.
AB  - D-Glucarate dehydratase from Escherichia coli (GlucD), a member of the enolase
      superfamily, catalyzes the dehydration of both D-glucarate and L-idarate to form
      5-keto-4-deoxy-D-glucarate (KDG). Previous mutagenesis and structural studies
      identified Lys 207 and the His 339-Asp 313 dyad as the general basic catalysts
      that abstract the C5 proton from L-idarate and D-glucarate, respectively, thereby
      initiating the reaction by formation of a stabilized enediolate anion
      intermediate [Gulick, A. M., Hubbard, B. K., Gerlt, J. A., and Rayment, I. (2000)
      Biochemistry 39, 4590-4602]. The vinylogous elimination of the 4-OH group from
      this intermediate presumably requires a general acid catalyst. The structure of
      GlucD with KDG and 4-deoxy-D-glucarate bound in the active site revealed that
      only His 339 and Asn 341 are proximal to the presumed position of the 4-OH
      leaving group. The N341D and N341L mutants of GlucD were constructed and
      subjected to both mechanistic and structural analyses. The N341L but not N341D
      mutant catalyzed the dehydrofluorination of 4-deoxy-4-fluoro-D-glucarate,
      demonstrating that in this mutant the initial proton abstraction from C5 can be
      decoupled from elimination of the leaving group from C4. The kinetic properties
      and structures of these mutants suggest that either Asn 341 participates in
      catalysis as the general acid that facilitates the departure of the 4-leaving
      group or is essential for proper positioning of His 339. In the latter scenario,
      His 339 would function not only as the general base that abstracts the C5 proton
      from D-glucarate but also as the general acid that catalyzes both the departure
      of the 4-OH group and the stereospecific incorporation of solvent hydrogen with
      retention of configuration to form the KDG product. The involvement of a single
      functional group in this reaction highlights the plasticity of the active site
      design in members of the enolase superfamily.

PMID- 11513585
TI  - Structure, dynamics, and thermodynamics of the structural domain of troponin C in
      complex with the regulatory peptide 1-40 of troponin I.
AB  - The structure of the calcium-saturated C-domain of skeletal troponin C (CTnC) in
      complex with a regulatory peptide comprising residues 1-40 (Rp40) of troponin I
      (TnI) was determined using nuclear magnetic resonance (NMR) spectroscopy. The
      solution structure determined by NMR is similar to the structure of the C-domain
      from intact TnC in complex with TnI(1)(-)(47) determined by X-ray crystallography
      [Vassylyev, D. G., Takeda, S., Wakatsuki, S., Maeda, K., and Maeda, Y. (1998)
      Proc. Natl. Acad. Sci. U.S.A. 95, 4847-4852]. Changes in the dynamic properties
      of CTnC.2Ca2+ induced by Rp40 binding were investigated using backbone amide
      (15)N NMR relaxation measurements. Analysis of NMR relaxation data allows for
      extraction of motional order parameters on a per residue basis, from which the
      contribution of changes in picosecond to nanosecond time scale motions to the
      conformational entropy associated with complex formation can be estimated. The
      results indicate that binding of Rp40 decreases backbone flexibility in CTnC,
      particularly at the end of the C-terminal helix. The backbone conformational
      entropy change (-TDeltaS) associated with binding of Rp40 to CTnC.2Ca2+
      determined from (15)N relaxation data is 9.6 +/- 0.7 kcal mol(-1) at 30 degrees
      C. However, estimation of thermodynamic quantities using a structural approach
      [Lavigne, P., Bagu, J. R., Boyko, R., Willard, L., Holmes, C. F., and Sykes, B.
      D. (2000) Protein Sci. 9, 252-264] reveals that the change in solvation entropy
      upon complex formation is dominant and overcomes the thermodynamic "cost"
      associated with "stiffening" of the protein backbone upon Rp40 binding.
      Additionally, backbone amide (15)N relaxation data measured at different
      concentrations of CTnC.2Ca2+.Rp40 reveal that the complex dimerizes in solution.
      Fitting of the apparent global rotational correlation time as a function of
      concentration to a monomer-dimer equilibrium yields a dimerization constant of
      approximately 8.3 mM.

PMID- 11513586
TI  - Electrostatic environment surrounding the activation loop phosphotyrosine in the
      oncoprotein v-Fps.
AB  - Autophosphorylation of Tyr-1073 in the activation loop of the oncoprotein v-Fps
      enhances the phosphoryl transfer reaction without influencing substrate, ATP, or
      metal ion binding affinities [Saylor, P., et al. (1998) Biochemistry 37, 17875
      17881]. A structural model of v-Fps, generated from the insulin receptor,
      indicates that pTyr-1073 chelates two arginines. Mutation of these residues to
      alanine (R1042A and R1066A) results in weakly phosphorylated enzymes, indicating
      that one electropositive center is insufficient for attaining maximum loop
      phosphorylation and concomitant high catalytic activity. While the turnover rate
      for R1066A is similar to that for a mutant lacking a phosphorylatable residue in
      the activation loop, the rate for R1042A is 50-fold slower. While solvent
      perturbation studies suggest that the former is due to a slow phosphoryl transfer
      step, the latter effect results from a slow conformational change in the mutant,
      potentially linked to motions in the catalytic loop. Binding of a stoichiometric
      quantity of Mg(2+) is essential for ATP binding and catalysis, while binding of
      an additional Mg(2+) ion activates further the wild-type enzyme. The affinity of
      the R1066A enzyme for the second Mg(2+) ion is 23-fold higher than that of the
      phosphorylated or unphosphorylated form of wild-type v-Fps, with substrate
      binding unaffected. Conversely, the affinity of R1066A for a substrate mimic
      lacking a phosphorylation site is 12-fold higher than that for the phosphorylated
      or unphosphorylated form of wild-type v-Fps, with binding of the second Mg(2+)
      ion unaffected. A comparison of these enzyme-independent parameters indicates
      that Arg-1042 and Arg-1066 induce strain in the active site in the repressed form
      of the enzyme. While this strain is not relieved in the phosphorylated form, the
      improvements in catalysis in activated v-Fps compensate for reduced metal and
      substrate binding affinities.

PMID- 11513587
TI  - DNA aptamers selected against the HIV-1 RNase H display in vitro antiviral
      activity.
AB  - The DNA polymerase of the human immunodeficiency virus type 1 reverse
      transcriptase (HIV-1 RT) is a target widely used to inhibit HIV-1 replication. In
      contrast, very few inhibitors of the RNase H activity associated with RT have
      been described, despite the crucial role played by this activity in viral
      proliferation. DNA ligands with a high affinity for the RNase H domain of HIV-1
      RT were isolated by systematic evolution of ligands by an exponential enrichment
      strategy (SELEX), using recombinant RTs with or without the RNase H domain. The
      selected oligonucleotides (ODNs) were able to inhibit in vitro the HIV-1 RNase H
      activity, while no effect was observed on cellular RNase H. We focused our
      interest on two G-rich inhibitory oligonucleotides. Model studies of the
      secondary structure of these ODNs strongly suggested that they were able to form
      G-quartets. In addition to the inhibition of HIV-1 RNase H observed in a cell
      free system, these ODNs were able to strongly diminish the infectivity of HIV-1
      in human infected cells. Oligonucleotides described here may serve as leading
      compounds for the development of specific inhibitors of this key retroviral
      enzyme activity.

PMID- 11513588
TI  - Mechanistic studies on thiamin phosphate synthase: evidence for a dissociative
      mechanism.
AB  - Thiamin phosphate synthase catalyzes the coupling of 4-methyl-5-(beta
      hydroxyethyl)thiazole phosphate (Thz-P) and 4-amino-5-(hydroxymethyl)-2
      methylpyrimidine pyrophosphate (HMP-PP) to give thiamin phosphate. In this paper,
      we demonstrate that 4-amino-5-(hydroxymethyl)-2-(trifluoromethyl)pyrimidine
      pyrophosphate (CF(3)-HMP-PP) is a very poor substrate [k(cat)(CH(3)) >
      7800k(cat)(CF(3))] and that 4-amino-5-(hydroxymethyl)-2-methoxypyrimidine
      pyrophosphate (CH(3)O-HMP-PP) is a good substrate [k(cat)(OCH(3)) >
      2.8k(cat)(CH(3))] for the enzyme. We also demonstrate that the enzyme catalyzes
      positional isotope exchange. These observations are consistent with a
      dissociative mechanism (S(N)1 like) for thiamin phosphate synthase in which the
      pyrimidine pyrophosphate dissociates to give a reactive pyrimidine intermediate
      which is then trapped by the thiazole moiety.

PMID- 11513589
TI  - Structural characterization of the enzyme-substrate, enzyme-intermediate, and
      enzyme-product complexes of thiamin phosphate synthase.
AB  - Thiamin phosphate synthase catalyzes the formation of thiamin phosphate from 4
      amino-5-(hydroxymethyl)-2-methylpyrimidine pyrophosphate and 5-(hydroxyethyl)-4
      methylthiazole phosphate. Several lines of evidence suggest that the reaction
      proceeds via a dissociative mechanism. The previously determined crystal
      structure of thiamin phosphate synthase in complex with the reaction products,
      thiamin phosphate and magnesium pyrophosphate, provided a view of the active site
      and suggested a number of additional experiments. We report here seven new
      crystal structures primarily involving crystals of S130A thiamin phosphate
      synthase soaked in solutions containing substrates or products. We prepared S130A
      thiamin phosphate synthase with the intent of characterizing the enzyme-substrate
      complex. Surprisingly, in three thiamin phosphate synthase structures, the active
      site density cannot be modeled as either substrates or products. For these
      structures, the best fit to the electron density is provided by a model that
      consists of independent pyrimidine, pyrophosphate, and thiazole phosphate
      fragments, consistent with a carbenium ion intermediate. The resulting carbenium
      ion is likely to be further stabilized by proton transfer from the pyrimidine
      amino group to the pyrophosphate to give the pyrimidine iminemethide, which we
      believe is the species that is observed in the crystal structures.

PMID- 11513590
TI  - Dissecting the electrostatic interactions and pH-dependent activity of a family
      11 glycosidase.
AB  - Previous studies of the low molecular mass family 11 xylanase from Bacillus
      circulans show that the ionization state of the nucleophile (Glu78, pK(a) 4.6)
      and the acid/base catalyst (Glu172, pK(a) 6.7) gives rise to its pH-dependent
      activity profile. Inspection of the crystal structure of BCX reveals that Glu78
      and Glu172 are in very similar environments and are surrounded by several
      chemically equivalent and highly conserved active site residues. Hence, there are
      no obvious reasons why their apparent pK(a) values are different. To address this
      question, a mutagenic approach was implemented to determine what features
      establish the pK(a) values (measured directly by (13)C NMR and indirectly by pH
      dependent activity profiles) of these two catalytic carboxylic acids. Analysis of
      several BCX variants indicates that the ionized form of Glu78 is preferentially
      stabilized over that of Glu172 in part by stronger hydrogen bonds contributed by
      two well-ordered residues, namely, Tyr69 and Gln127. In addition, theoretical
      pK(a) calculations show that Glu78 has a lower pK(a) value than Glu172 due to a
      smaller desolvation energy and more favorable background interactions with
      permanent partial charges and ionizable groups within the protein. The pK(a)
      value of Glu172 is in turn elevated due to electrostatic repulsion from the
      negatively charged glutamate at position 78. The results also indicate that all
      of the conserved active site residues act concertedly in establishing the pK(a)
      values of Glu78 and Glu172, with no particular residue being singly more
      important than any of the others. In general, residues that contribute positive
      charges and hydrogen bonds serve to lower the pK(a) values of Glu78 and Glu172.
      The degree to which a hydrogen bond lowers a pK(a) value is largely dependent on
      the length of the hydrogen bond (shorter bonds lower pK(a) values more) and the
      chemical nature of the donor (COOH > OH > CONH(2)). In contrast, neighboring
      carboxyl groups can either lower or raise the pK(a) values of the catalytic
      glutamic acids depending upon the electrostatic linkage of the ionization
      constants of the residues involved in the interaction. While the pH optimum of
      BCX can be shifted from -1.1 to +0.6 pH units by mutating neighboring residues
      within the active site, activity is usually compromised due to the loss of
      important ground and/or transition state interactions. These results suggest that
      the pH optima of an enzyme might be best engineered by making strategic amino
      acid substitutions, at positions outside of the "core" active site, that
      electrostatically influence catalytic residues without perturbing their immediate
      structural environment.

PMID- 11513591
TI  - Hydrophobic core manipulations in ribonuclease T1.
AB  - Differential scanning calorimetry, urea denaturation, and X-ray crystallography
      were combined to study the structural and energetic consequences of refilling an
      engineered cavity in the hydrophobic core of RNase T1 with CH(3), SH, and OH
      groups. Three valines that cluster together in the major hydrophobic core of T1
      were each replaced with Ala, Ser, Thr, and Cys. Compared to the wild-type
      protein, all these mutants reduce the thermodynamic stability of the enzyme
      considerably. The relative order of stability at all three positions is as
      follows: Val > Ala approximately equal to Thr > Ser. The effect of introducing a
      sulfhydryl group is more variable. Surprisingly, a Val --> Cys mutation in a
      hydrophobic environment can be as or even more destabilizing than a Val --> Ser
      mutation. Furthermore, our results reveal that the penalty for introducing an OH
      group into a hydrophobic cavity is roughly the same as the gain obtained from
      filling the cavity with a CH(3) group. The inverse equivalence of the behavior of
      hydroxyl and methyl groups seems to be crucial for the unique three-dimensional
      structure of the proteins. The importance of negative design elements in this
      context is highlighted.

PMID- 11513592
TI  - Phenylalanine and tryptophan scanning mutagenesis of CYP3A4 substrate recognition
      site residues and effect on substrate oxidation and cooperativity.
AB  - Phenylalanine and/or tryptophan scanning mutagenesis was performed at 15 sites
      within CYP3A4 proposed to be involved in substrate specificity or cooperativity.
      The sites were chosen on the basis of previous studies or from a comparison with
      the structure of P450(eryF) containing two molecules of androstenedione. The
      function of the 25 mutants was assessed in a reconstituted system using
      progesterone, testosterone, 7-benzyloxy-4-(trifluoromethyl)coumarin (7-BFC), and
      alpha-naphthoflavone (ANF) as substrates. CYP3A4 wild type displayed sigmoidal
      kinetics of ANF 5,6-oxide formation and 7-BFC debenzylation. Analysis of 12
      mutants with significant steroid hydroxylase activity showed a lack of positive
      correlation between ANF oxidation and stimulation of progesterone 6beta
      hydroxylation by ANF, indicating that ANF binds at two sites within CYP3A4. 7-BFC
      debenzylation was stimulated by progesterone and ANF, and 7-BFC did not inhibit
      testosterone or progesterone 6beta-hydroxylation. Correlational analysis showed
      no relationship between 7-BFC debenzylation and either progesterone or
      testosterone 6beta-hydroxylation. These data are difficult to explain with a two
      site model of CYP3A4 but suggest that three subpockets exist within the active
      site. Interestingly, classification of the mutants according to their ability to
      oxidize the four substrates utilized in this study suggested that substrates do
      bind at preferred locations in the CYP3A4 binding pocket.

PMID- 11513593
TI  - Crystal structure of human type III 3alpha-hydroxysteroid dehydrogenase/bile acid
      binding protein complexed with NADP(+) and ursodeoxycholate.
AB  - The crystal structure of human type III 3alpha-hydroxysteroid dehydrogenase
      (HSD)/bile acid binding protein (AKR1C2) complexed with NADP(+) and 3alpha,7beta
      dihydroxy-5beta-cholanic acid (ursodeoxycholate) at 3.0 A resolution is
      presented. Thus, the three-dimensional structure has now been solved for a human
      HSD member of the aldo-keto reductase superfamily. AKR1C2 is implicated in the
      prostatic production of the potent androgen 5alpha-dihydrotestosterone and the
      hepatic transport of bile acids. It also catalyzes the formation of the
      neurosteroid 3alpha-hydroxy-5alpha-pregnan-20-one in the central nervous system,
      and its allosteric modulation by fluoxetine has been linked to the use of this
      drug for premenstrual dsyphoria. Like other members of the superfamily, AKR1C2
      folds into an alpha/beta-barrel and binds NADP(+) in an extended conformation.
      The carboxylate of ursodeoxycholate binds to AKR1C2 in the oxyanion hole at the
      active site. More interestingly, the orientation of ursodeoxycholate is
      essentially "backwards" and "upside-down" from that observed for testosterone in
      the related rat 3alpha-HSD.NADP(+).testosterone ternary complex, where
      testosterone assumes the position of a 3-ketosteroid substrate. The orientation
      of ursodeoxycholate is thus similar to that expected of a 17beta-HSD substrate.
      The ternary structure explains the ability of AKR1C2 to catalyze 3alpha-, 17beta
      , and 20alpha-HSD reactions. Comparison of the steroid binding pocket of AKR1C2
      with that of rat 3alpha-HSD reveals significant differences in the positions of
      conserved and nonconserved loop residues, providing insights into the structural
      basis for the functional flexibility that is observed in all the human 3alpha-HSD
      isoforms but not in the rat isoform.

PMID- 11513594
TI  - Identification of functionally important amino-terminal arginines of
      Agrobacterium tumefaciens ADP-glucose pyrophosphorylase by alanine scanning
      mutagenesis.
AB  - Treatment of the Agrobacterium tumefaciens ADP-glucose pyrophosphorylase with the
      arginyl reagent phenylglyoxal resulted in complete desensitization to fructose 6
      phosphate (F6P) activation, and partial desensitization to pyruvate activation.
      The enzyme was protected from desensitization by ATP, F6P, pyruvate, and
      phosphate. Alignment studies revealed that this enzyme contains arginine residues
      in the amino-terminal region that are relatively conserved in similarly regulated
      ADP-glucose pyrophosphorylases. To functionally evaluate the role(s) of these
      arginines, alanine scanning mutagenesis was performed to generate the following
      enzymes: R5A, R11A, R22A, R25A, R32A, R33A, R45A, and R60A. All of the enzymes,
      except R60A, were successfully expressed and purified to near homogeneity. Both
      the R5A and R11A enzymes displayed desensitization to pyruvate, partial
      activation by F6P, and increased sensitivity to phosphate inhibition. Both the
      R22A and R25A enzymes exhibited reduced V(max) values in the absence of
      activators, lower apparent affinities for ATP and F6P, and reduced sensitivities
      to phosphate. The presence of F6P restored R22A enzyme activity, while the R25A
      enzyme exhibited only approximately 1.5% of the wild-type activity. The R32A
      enzyme displayed an approximately 11.5-fold reduced affinity for F6P while
      exhibiting behavior identical to that of the wild type with respect to pyruvate
      activation. Both the R33A and R45A enzymes demonstrated a higher activity than
      the wild-type enzyme in the absence of activators, no response to F6P, partial
      activation by pyruvate, and desensitization to phosphate inhibition. These
      altered enzymes were also insensitive to phenylglyoxal. The data demonstrate
      unique functional roles for these arginines and the presence of separate subsites
      for the activators.

PMID- 11513595
TI  - Dissecting the cofactor-dependent and independent bindings of PDE4 inhibitors.
AB  - Type 4 phosphodiesterases (PDE4s) are metallohydrolases that catalyze the
      hydrolysis of cAMP to AMP. At the bottom of its active site lie two divalent
      metal ions in a binuclear motif which are involved in both cAMP binding and
      catalysis [(2000) Science 288, 1822-1825; (2000) Biochemistry 39, 6449-6458].
      Using a SPA-based equilibrium [(3)H]rolipram binding assay, we have determined
      that Mg(2+), Mn(2+), and Co(2+) all mediated a high-affinity (K(d) between 3 and
      8 nM) and near stoichiometric (R)-rolipram binding to PDE4. In their absence, (R)
      rolipram binds stoichiometrically to the metal ion-free apoenzyme with a K(d) of
      approximately 150 nM. The divalent cation dose responses in mediating the high
      affinity rolipram/PDE4 interaction mirror their efficacy in catalysis, suggesting
      that both metal ions of the holoenzyme are involved in mediating the high
      affinity (R)-rolipram/PDE4 interaction. The specific rolipram binding to the apo-
      and holoenzyme is differentially displaced by cAMP, AMP, and other inhibitors,
      providing a robust tool to dissect the components of metal ion-dependent and
      independent PDE4/ligand interactions. cAMP binds to the holoenzyme with a K(s) of
      1.9 microM and nonproductively to the apoenzyme with a K(d) of 179 microM. In
      comparison, AMP binds to the holo- and apoenzyme with K(d) values of 7 and 11 mM,
      respectively. The diminished Mg(2+)-dependent component of AMP binding to PDE4
      suggests that most of the Mg(2+)/phosphate interaction in the cAMP/PDE4 complex
      is disrupted upon the hydrolysis of the cyclic phosphoester bond, leading to the
      rapid release of AMP.

PMID- 11513596
TI  - On the multiple functional roles of the active site histidine in catalysis and
      allosteric regulation of Escherichia coli glucosamine 6-phosphate deaminase.
AB  - The active site of glucosamine-6-phosphate deaminase (EC 3.5.99.6, formerly
      5.3.1.10) from Escherichia coli was first characterized on the basis of the
      crystallographic structure of the enzyme bound to the competitive inhibitor 2
      amino-2-deoxy-glucitol 6-phosphate. The structure corresponds to the R allosteric
      state of the enzyme; it shows the side-chain of His143 in close proximity to the
      O5 atom of the inhibitor. This arrangement suggests that His143 could have a role
      in the catalysis of the ring-opening step of glucosamine 6-phosphate whose alpha
      anomer is the true substrate. The imidazole group of this active-site histidine
      contacts the carboxy groups from Glu148 and Asp141, via its Ndelta1 atom [Oliva
      et al. (1995) Structure 3, 1323-1332]. These interactions change in the T state
      because the side chain of Glu148 moves toward the allosteric site, leaving at the
      active site the dyad Asp141-His143 [Horjales et al. (1999) Structure 7, 527-536].
      In this research, a dual approach using site-directed mutagenesis and controlled
      chemical modification of histidine residues has been used to investigate the role
      of the active-site histidine. Our results support a multifunctional role of
      His143; in the forward reaction, it is involved in the catalysis of the ring
      opening step of the substrate, glucosamine 6-P. In the reverse reaction, the
      substrate fructose 6-P binds in its open chain, carbonylic form. The role of
      His143 in the binding of both glucosamine 6-P and reaction intermediates in their
      extended-chain forms was demonstrated by binding experiments using the reaction
      intermediate analogue, 2-amino-2-deoxy-D-glucitol 6-phosphate. His143 was also
      shown to be a critical residue for the conformational coupling between active and
      allosteric sites. From the pH dependence of the reactivity of the active site
      histidine to diethyl dicarbonate, we observed a pK(a) change of 1.2 units to the
      acid side when the enzyme undergoes the allosteric T to R transition during which
      the side chain of Glu148 moves toward the active site. The kinetic study of the
      Glu148-Gln mutant deaminase shows that the loss of the carboxy group and its
      replacement with the corresponding amide modifies the k(cat) versus pH profile of
      the enzyme, suggesting that the catalytic step requiring the participation of
      His143 has become rate-limiting. This, in turn, indicates that the interaction
      Glu148-His143 in the wild-type enzyme in the R state contributes to make the
      enzyme functional over a wide pH range.

PMID- 11513597
TI  - The role of Tyr248 probed by mutant bovine carboxypeptidase A: insight into the
      catalytic mechanism of carboxypeptidase A.
AB  - We have investigated the function of Tyr248 using bovine wild-type CPA and its
      Y248F and Y248A mutants to find that the K(M) values were increased by 4.5-11
      fold and the k(cat) values were reduced by 4.5-10.7-fold by the replacement of
      Tyr248 with Phe for the hydrolysis of hippuryl-L-Phe (HPA) and N-[3-(2
      furyl)acryloyl]-Phe-Phe (FAPP), respectively. In the case of O-(trans-p
      chlorocinnamoyl)-L-beta-phenyllactate (ClCPL), an ester substrate, the K(M) value
      was increased by 2.5-fold, and the k(cat) was reduced by 20-fold. The replacement
      of Tyr248 with Ala decreased the k(cat) values by about 18- and 237-fold for HPA
      and ClCPL, respectively, demonstrating that the aromatic ring of Tyr248 plays a
      critical role in the enzymic reaction. The increases of the K(M) values were only
      6- and 5-fold for HPA and ClCPL, respectively. Thus, the present study indicates
      clearly that Tyr248 plays an important role not only in the binding of substrate
      but also in the enzymic hydrolysis. The kinetic results may be rationalized by
      the proposition that the phenolic hydroxyl of Tyr248 forms a hydrogen bond with
      the zinc-bound water molecule, causing further activation of the water molecule
      by reducing its pK(a) value. The pH dependency study of k(cat) values and the
      solvent isotope effects also support the proposition. A unified catalytic
      mechanism is proposed that can account for the different kinetic behavior
      observed in the CPA-catalyzed hydrolysis of peptide and ester substrates.

PMID- 11513598
TI  - A kinetic analysis of the catalase activity of myeloperoxidase.
AB  - The predominant physiological activity of myeloperoxidase is to convert hydrogen
      peroxide and chloride to hypochlorous acid. However, this neutrophil enzyme also
      degrades hydrogen peroxide to oxygen and water. We have undertaken a kinetic
      analysis of this reaction to clarify its mechanism. When myeloperoxidase was
      added to hydrogen peroxide in the absence of reducing substrates, there was an
      initial burst phase of hydrogen peroxide consumption followed by a slow steady
      state loss. The kinetics of hydrogen peroxide loss were precisely mirrored by the
      kinetics of oxygen production. Two mols of hydrogen peroxide gave rise to 1 mol
      of oxygen. With 100 microM hydrogen peroxide and 6 mM chloride, half of the
      hydrogen peroxide was converted to hypochlorous acid and the remainder to oxygen.
      Superoxide and tyrosine enhanced the steady-state loss of hydrogen peroxide in
      the absence of chloride. We propose that hydrogen peroxide reacts with the ferric
      enzyme to form compound I, which in turn reacts with another molecule of hydrogen
      peroxide to regenerate the native enzyme and liberate oxygen. The rate constant
      for the two-electron reduction of compound I by hydrogen peroxide was determined
      to be 2 x 10(6) M(-1) s(-1). The burst phase occurs because hydrogen peroxide and
      endogenous donors are able to slowly reduce compound I to compound II, which
      accumulates and retards the loss of hydrogen peroxide. Superoxide and tyrosine
      drive the catalase activity because they reduce compound II back to the native
      enzyme. The two-electron oxidation of hydrogen peroxide by compound I should be
      considered when interpreting mechanistic studies of myeloperoxidase and may
      influence the physiological activity of the enzyme.

PMID- 11513599
TI  - Hormonal regulation of peripheral benzodiazepine receptor binding properties is
      mediated by subunit interaction.
AB  - The peripheral benzodiazepine receptor (PBR) is composed of three subunits with
      molecular masses of 18, 30, and 32 kDa. Many physiological functions have been
      attributed to the PBR, including regulation of steroidogenesis. Furthermore, the
      PBR itself is under hormonal regulation. In the current study, we investigated
      the role of female gonadal sex hormones in the regulation of PBR expression in
      steroidogenic and nonsteroidogenic tissues. To accomplish this, adult female rats
      were pharmacologically castrated using chronic administration of the gonadotropin
      releasing hormone agonist decapeptyl (triptorelin-D-Trp(6)-LHRH). Half of these
      rats received 17beta-estradiol as hormone replacement, while a control group
      received daily injections of vehicle only. We found that PBR binding capacity
      dropped by 40 and 48% in ovaries and adrenals, respectively, following decapeptyl
      administration, as opposed to no change in the kidney. This down-regulation of
      PBR densities was prevented by estradiol replacement. We did not find evidence
      for transcriptional, posttranscriptional, and translational mechanisms in this
      decapeptyl-induced down-regulation. In contrast, immunoprecipitation of the PBR
      complex, using antibodies against the 18- and 32-kDa subunits of the complex,
      demonstrated that there were changes in PBR subunit interactions, consistent with
      the down-regulation of PBR binding capacity. These findings represent a novel
      hormone-dependent posttranslational regulatory mechanism.

PMID- 11513600
TI  - Soybean lipoxygenase-1 oxygenates synthetic polyenoic fatty acids with an altered
      positional specificity: evidence for inverse substrate alignment.
AB  - The positional specificity is the decisive enzyme property for classification of
      lipoxygenases and for the currently used lipoxygenase nomenclature. It has been
      reported before that soybean lipoxygenase-1, which oxygenates polyenoic fatty
      acids at alkaline pH to the corresponding n - 6 hydroperoxy derivative, exhibits
      a different positional specificity when either the reaction conditions or the
      substrate structure is altered. To investigate the impact of structural substrate
      modifications on the positional specificity of this enzyme and to force an
      inverse substrate binding, we synthesized arachidonic acid analogues modified at
      the omega-terminus. Care was taken that the double bond system remained unchanged
      so that hydrogen abstraction from all three bisallylic methylenes was
      theoretically possible. We found that omega-modification of arachidonic acid
      leads to an impaired substrate affinity and a reduced reaction rate, but we did
      not detect any 5-lipoxygenation products, suggesting that structural modification
      of the omega-end may not be sufficient to force an inverse substrate orientation.
      However, when both ends of the fatty acid chain (omega-terminus and free
      carboxylate) were modified simultaneously, a considerable share of 5
      lipoxygenation products was detected. These results indicate that introduction of
      polar or bulky groups at the methyl terminus of polyenoic fatty acids was not
      sufficient to force an inverse substrate orientation. However, simultaneous
      introduction of an omega-OH group and methylation of the carboxylate led to
      formation of significant 5-lipoxygenation products, suggesting an inverse head to
      tail substrate orientation.

PMID- 11513601
TI  - Real-time kinetics of ligand/cell surface receptor interactions in living cells:
      binding of epidermal growth factor to the epidermal growth factor receptor.
AB  - We describe a system for extending stopped-flow analysis to the kinetics of
      ligand capture and release by cell surface receptors in living cells. While most
      mammalian cell lines cannot survive the shear forces associated with turbulent
      stopped-flow mixing, we determined that a murine hematopoietic precursor cell
      line, 32D, is capable of surviving rapid mixing using flow rates as great as 4.0
      mL/s, allowing rapid processes to be quantitated with dead times as short as 10
      ms. 32D cells do not express any endogenous epidermal growth factor (EGF)
      receptor or other ErbB family members and were used to establish monoclonal cell
      lines stably expressing the EGF receptor. Association of fluorescein-labeled H22Y
      murine EGF (F-EGF) to receptor-expressing 32D cells was observed by measuring
      time-dependent changes in fluorescence anisotropy following rapid mixing.
      Dissociation of F-EGF from EGF-receptor-expressing 32D cells was measured both by
      chase experiments using unlabeled mEGF and by experiments in which equilibrium
      was perturbed by dilution. Comparison of these dissociation experiments showed
      that little, if any, ligand-induced dissociation occurs in the chase dissociation
      experiments. Data from a series of association and dissociation experiments,
      performed at various concentrations of F-EGF in the nanomolar range and at
      multiple cell densities, were simultaneously analyzed using global analysis
      techniques and fit to a two independent receptor-class model. Our analysis is
      consistent with the presence of two distinct receptor populations having
      association rate constants of k(on1) = 8.6 x 10(6) M(-1) s(-1) and k(on2) = 2.4 x
      10(6) M(-1) s(-1) and dissociation rate constants of k(off1) = 0.17 x 10(-2) s(
      1) and k(off2) = 0.21 x 10(-2) s(-1). The magnitudes of these parameters suggest
      that under physiological conditions, in which cells are transiently exposed to
      nanomolar concentrations of ligand, ligand capture and release may function as
      the first line of regulation of the EGF receptor-induced signal transduction
      cascade.

PMID- 11513602
TI  - Mechanistic effects of autophosphorylation on receptor tyrosine kinase catalysis:
      enzymatic characterization of Tie2 and phospho-Tie2.
AB  - Activation of receptor tyrosine kinases by autophosphorylation is one of the most
      common and critical transformations in signal transduction, yet its role in
      catalysis remains controversial. Autophosphorylation of the angiogenic receptor
      tyrosine kinase Tie2 was studied in terms of the autophosphorylation sites,
      sequence of phosphorylation at these sites, kinetic effects, and mechanistic
      consequences. Isoelectric focusing electrophoresis and mass spectrometric
      analysis of a Tie2 autophosphorylation time course showed that Tyr992 on the
      putative activation loop was phosphorylated first followed by Tyr1108 in the C
      terminal tail (previously unidentified autophosphorylation site).
      Autophosphorylation of Tie2 to produce pTie2 resulted in a 100-fold increase in
      k(cat) and a 460-fold increase in k(cat)/K(m). Viscosity studies showed that the
      unphosphorylated Tie2 was partially limited by product diffusion ((k(cat))(eta) =
      0.67 +/- 0.06), while product release was more rate-limiting ((k(cat))(eta) =
      0.94 +/- 0.08) for autophosphorylated Tie2 (pTie2). Furthermore,
      autophosphorylation did not significantly affect the phosphoacceptor dissociation
      constants. There was a significant (k(cat))(H)/(k(cat))(D) solvent isotope effect
      (SIE) for unphosphorylated Tie2 (2.42 +/- 0.12) and modest SIE (1.28 +/- 0.04)
      for pTie2, which is consistent with the chemistry step being more rate-limiting
      for Tie2 as compared to pTie2. The pH-rate profiles of Tie2 and pTie2 revealed a
      >0.5 unit shift in the pK(a) values of catalytically relevant ionizable residues
      upon autophosphorylation. The shift in rate-limiting step will result in a
      different distribution of enzyme pools (e.g., E, E*S, E*P, etc.) which may
      modulate the susceptibility to inhibition. Tie2 and pTie2 were profiled with a
      panel of known ATP-competitive kinase inhibitors. Tie2 activation perturbs
      catalytic residue ionizations, shifts the rate-limiting step to almost exclusive
      diffusion-control, and transforms the kinase into a more perfect catalyst.

PMID- 11513603
TI  - Thermodynamics of HMGB1 interaction with duplex DNA.
AB  - The high mobility group protein HMGB1 is a small, highly abundant protein that
      binds to DNA in a non-sequence-specific manner. HMGB1 consists of 2 DNA binding
      domains, the HMG boxes A and B, followed by a short basic region and a continuous
      stretch of 30 glutamate or aspartate residues. Isothermal titration calorimetry
      was used to characterize the binding of HMGB1 to the double-stranded model DNAs
      poly(dAdT).(dTdA) and poly(dGdC).(dCdG). To elucidate the contribution of the
      different structural motifs to DNA binding, calorimetric measurements were
      performed comparing the single boxes A and B, the two boxes plus or minus the
      basic sequence stretch (AB(bt) and AB), and the full-length HMGB1 protein.
      Thermodynamically, binding of HMGB1 and all truncated constructs to duplex DNA
      was characterized by a positive enthalpy change at 15 degrees C. From the slopes
      of the temperature dependence of the binding enthalpies, heat capacity changes of
      -0.129 +/- 0.02 and -0.105 +/- 0.05 kcal mol(-1) K(-1) were determined for box A
      and full-length HMGB1, respectively. Significant differences in the binding
      characteristics were observed using full-length HMGB1, suggesting an important
      role for the acid tail in modulating DNA binding. Moreover, full-length HMGB1
      binds differently these two DNA templates: binding to poly(dAdT).(dTdA) was
      cooperative, had a larger apparent binding site size, and proceeded with a much
      larger unfavorable binding enthalpy than binding to poly(dGdC).(dCdG).

PMID- 11513604
TI  - Cleavage of 3',5'-pyrophosphate-linked dinucleotides by ribonuclease A and
      angiogenin.
AB  - Recently, 3',5'-pyrophosphate-linked 2'-deoxyribodinucleotides were shown to be
      >100-fold more effective inhibitors of RNase A superfamily enzymes than were the
      corresponding monophosphate-linked (i.e., standard) dinucleotides. Here, we have
      investigated two ribo analogues of these compounds, cytidine 3'-pyrophosphate (P'
      ->5') adenosine (CppA) and uridine 3'-pyrophosphate (P'-->5') adenosine (UppA),
      as potential substrates for RNase A and angiogenin. CppA and UppA are cleaved
      efficiently by RNase A, yielding as products 5'-AMP and cytidine or uridine
      cyclic 2',3'-phosphate. The k(cat)/K(m) values are only 4-fold smaller than for
      the standard dinucleotides CpA and UpA, and the K(m) values (10-16 microM) are
      lower than those reported for any earlier small substrates (e.g., 500-700 microM
      for CpA and UpA). The k(cat)/K(m) value for CppA with angiogenin is also only
      severalfold smaller than for CpA, but the effect of lengthening the
      internucleotide linkage on K(m) is more modest. Ribonucleotide 3',5'
      pyrophosphate linkages were proposed previously to exist in nature as chemically
      labile intermediates in the pathway for the generation of cyclic 2',3'-phosphate
      termini in various RNAs. We demonstrate that in fact they are relatively stable
      (t(1/2) > 15 days for uncatalyzed degradation of UppA at pH 6 and 25 degrees C)
      and that cleavage in vivo is most likely enzymatic. Replacements of the RNase A
      catalytic residues His12 and His119 by alanine reduce activity toward UppA by
      approximately 10(5)-and 10(3.3)-fold, respectively. Thus, both residues play
      important roles. His12 probably acts as a base catalyst in cleavage of UppA (as
      with RNA). However, the major function of His119 in RNA cleavage, protonation of
      the 5'-O leaving group, is not required for UppA cleavage because the pK(a) of
      the leaving group is much lower than that for RNA substrates. A crystal structure
      of the complex of RNase A with 2'-deoxyuridine 3'-pyrophosphate (P'-->5')
      adenosine (dUppA), determined at 1.7 A resolution, together with models of the
      UppA complex based on this structure suggest that His119 contributes to UppA
      cleavage through a hydrogen bond with a nonbridging oxygen atom in the
      pyrophosphate and through pi-pi stacking with the six-membered ring of adenine.

PMID- 11513605
TI  - Protein-protein interaction using tryptophan analogues: novel spectroscopic
      probes for toxin-elongation factor-2 interactions.
AB  - Previously, we characterized the role of the three naturally occurring Trp
      residues (W-417, -466, and -558) in the catalytic mechanism of the toxin-enzyme
      produced by Pseudomonas aeruginosa [Beattie and Merrill (1999) J. Biol. Chem.
      274, 15646-15654]. However, the use of intrinsic Trp fluorescence to study toxin
      eEF-2 interaction is inherently limited since the spectral properties of the
      various Trp residues in both proteins cannot easily be distinguished. To
      facilitate the study of the protein-protein interaction by Trp fluorescence
      spectroscopy, the Trp residues in the catalytic domain of exotoxin A were
      replaced with the amino acid analogues 4-fluorotryptophan, 5-fluorotryptophan, 5
      hydroxytryptophan, and 7-azatryptophan. The incorporation of analogues was
      achieved by using a tightly regulated promoter, pBAD, and expressing the protein
      in a Trp auxotrophic strain of Escherichia coli, BL21, in a minimal medium
      containing the appropriate tryptophan analogue. Quantitative spectral analysis of
      the analogue-containing proteins using the Decompose program indicated that we
      had achieved 87-100% incorporation efficiency depending on the Trp analogue being
      used. Electrospray mass spectrometry analysis verified that we had achieved
      nearly total replacement of the L-tryptophan residues within the catalytic domain
      of exotoxin A with the tryptophan analogues 5-fluorotryptophan and 4
      fluorotryptophan. The analogue-substituted proteins showed a variation in their
      catalytic activities with k(cat) values ranging from 6-fold (4-fluorotryptophan)
      to 260-fold (5-hydroxytryptophan) lower than the natural enzyme, which was in
      agreement with previous data using site-directed mutagenesis [Beattie et al.
      (1996) Biochemistry 35, 15134-15142]. However, the analogue-incorporated enzymes
      did not show any significant change in their ability to bind NAD(+) as substrate,
      as determined from a fluorescence-binding assay. The spectral properties of the
      various analogue-incorporated proteins were evaluated and compared with those of
      the native protein. Furthermore, selective excitation of the 5-hydroxytryptophan
      incorporated toxin was exploited to study its interaction with the elongation
      factor-2 substrate by fluorescence resonance energy transfer to an acceptor
      chromophore located on the elongation factor-2 protein. The binding between the
      toxin-enzyme and elongation factor-2 was shown to be independent of the NAD(+)
      substrate (983 +/- 63 nM) and showed a small dependence upon the ionic strength
      of the solution.

PMID- 11513606
TI  - Kinetics of registry selection of chimeric peptides binding to MHC II.
AB  - Major histocompatability complex type II proteins (MHC II) are alphabeta
      heterodimeric glycoproteins that present peptides to the T cell receptor (TCR) of
      CD4(+) T-cells. This presentation may result in activation of these T-cells,
      depending on the nature of the peptide. Peptides interact specifically with MHC
      II with nine peptide amino acid positions, and the corresponding MHC II pocket
      positions are usually labeled P1-P9. However, the length of peptides binding to
      MHC II may be greater than nine amino acids, and therefore these peptides may
      potentially bind to the MHC II in more than one registry. To investigate the
      mechanism by which a long peptide binds to I-E(k), a murine MHC II, a chimeric
      peptide with two nonoverlapping registries, f-IAYLKQATKQLRMATPLLMR was designed.
      The IAYLKQATK peptide segment is based on moth cytochrome c 95-103 (MCC 95-103),
      and the QLRMATPLLMR segment is based on murine Ii CLIP 89-99 M90L (Ii CLIP 89-99
      M90L). This chimeric peptide forms two isomeric complexes. The MCC and Ii CLIP
      registries dissociate from I-E(k) with t(1/2) values of >>800 and 4.94 h,
      respectively. The registry composition of this MHC II/chimeric peptide complex
      was found to change as a function of time in approaching thermodynamic
      equilibrium: the results are consistent with a kinetic model that involves no
      intramolecular isomer interconversion. The model depicts uncorrelated binding to
      the MHC II determined by relative association rates to the two registries. This
      is followed by dissociation and subsequent rebinding, leading ultimately to a
      preponderance of the most stable complex. Similar results were obtained at pH
      5.3. The behavior of this chimeric peptide approximates the binding of a 1:1
      solution mixture of two peptides to MHC II, where the more stable complex is
      selected over time. We have also found that a chimeric peptide and a human MHC
      II, HLA-DR40401, form isomers with relative association rates to DR0401 at pH 5.3
      of 15% for one isomer and 85% for the second isomer.

PMID- 11513607
TI  - Metal ion-independent association of factor VIII subunits and the roles of
      calcium and copper ions for cofactor activity and inter-subunit affinity.
AB  - Factor VIII circulates as a divalent metal ion-dependent heterodimer comprised of
      a light chain (LC) and a heavy chain (HC). Reassociation of factor VIII subunits
      was assessed using fluorescence energy transfer where LC and HC were labeled with
      acrylodan (Ac; fluorescence donor) and fluorescein-5-maleimide (Fl; fluorescence
      acceptor), respectively. The reduction of donor fluorescence due to the acceptor
      was used as an indicator of binding. Subunits associated with high affinity (K(d)
      = 53.8 nM) in the absence of metal ion and presence of EDTA. However, this
      product showed no cofactor activity, as measured by a factor Xa generation assay.
      In the presence of 25 mM Ca(2+), no increase in the intersubunit affinity was
      observed (K(d) = 48.7 nM) but specific activity of the cofactor was approximately
      30% that of native factor VIII. At saturating levels of Fl-HC relative to Ac-LC,
      donor fluorescence decreased to 79.3 and 73.5% of its original value in the
      absence and presence of Ca(2+), respectively. Thrombin cleaved the heterodimers
      that were associated in the absence or presence of Ca(2+) with similar
      efficiency, indicating that the lack of activity was not the result of a defect
      in activation. Cu(2+) (0.5 microM) increased the intersubunit affinity by
      approximately 100 fold (K(d) = 0.52 nM) and the specific activity to
      approximately 60% of native factor VIII. The former effect was independent of
      Ca(2+), whereas the latter effect required Ca(2+). These results indicate that
      the intersubunit association in factor VIII is primarily metal-ion independent
      while divalent metal ions serve specific roles. Ca(2+) appears essential to
      promote the active conformation of factor VIII while Cu(2+) primarily enhances
      the intersubunit affinity.

PMID- 11513608
TI  - Tethered processivity of the vitamin K-dependent carboxylase: factor IX is
      efficiently modified in a mechanism which distinguishes Gla's from Glu's and
      which accounts for comprehensive carboxylation in vivo.
AB  - The vitamin K-dependent (VKD) carboxylase binds VKD proteins via their propeptide
      and converts Glu's to gamma-carboxylated Glu's, or Gla's, in the Gla domain.
      Multiple carboxylation is required for activity, which could be achieved if the
      carboxylase is processive. In the only previous study to test for this
      capability, an indirect assay was used which suggested processivity; however, the
      efficiency was poor and raised questions regarding how full carboxylation is
      accomplished. To unequivocally determine if the carboxylase is processive and if
      it can account for comprehensive carboxylation in vivo, as well as to elucidate
      the enzyme mechanism, we developed a direct test for processivity. The in vitro
      carboxylation of a complex containing carboxylase and full-length factor IX (fIX)
      was challenged with an excess amount of a distinguishable fIX variant.
      Remarkably, carboxylation of fIX in the complex was completely unaffected by the
      challenge protein, and comprehensive carboxylation was achieved, showing
      conclusively that the carboxylase is processive and highly efficient. These
      studies also showed that carboxylation of individual fIX/carboxylase complexes
      was nonsynchronous and implicated a driving force for the reaction which requires
      the carboxylase to distinguish Glu's from Gla's. We found that the Gla domain is
      tightly associated with the carboxylase during carboxylation, blocking the access
      of a small peptide substrate (EEL). The studies describe the first analysis of
      preformed complexes, and the rate for full-length, native fIX in the complex was
      equivalent to that of the substrate EEL. Thus, intramolecular movement within the
      Gla domain to reposition new Glu's for catalysis is as rapid as diffusion-limited
      positioning of a small substrate, and the Gla domain is not sterically
      constrained by the rest of the fIX molecule during carboxylation. The rate of
      carboxylation of fIX in the preformed complex was 24-fold higher than for fIX
      modified by free carboxylase, which supports carboxylase processivity and which
      indicates that binding and/or release is the rate-limiting step in protein
      carboxylation. These data indicate a model of tethered processivity, in which the
      VKD proteins remain bound to the carboxylase throughout the reaction via their
      propeptide, while the Gla domain undergoes intramolecular movement to reposition
      new Glu's for catalysis to ultimately achieve comprehensive carboxylation.

PMID- 11513609
TI  - Differences in the oligomeric states of the LDH-like L-MalDH from the
      hyperthermophilic archaea Methanococcus jannaschii and Archaeoglobus fulgidus.
AB  - L-Malate (MalDH) and L-lactate (LDH) dehydrogenases belong to the same family of
      NAD-dependent enzymes. To gain insight into molecular relationships within this
      family, we studied two hyperthermophilic (LDH-like) L-MalDH (proteins with LDH
      like structure and MalDH enzymatic activity) from the archaea Archaeoglobus
      fulgidus (Af) and Methanococcus jannaschii (Mj). The structural parameters of
      these enzymes determined by neutron scattering and analytical centrifugation
      showed that the Af (LDH-like) L-MalDH is a dimer whereas the Mj (LDH-like) L
      MalDH is a tetramer. The effects of high temperature, cofactor binding, and high
      phosphate concentration were studied. They did not modify the oligomeric state of
      either enzyme. The enzymatic activity of the dimeric Af (LDH-like) L-MalDH is
      controlled by a pH-dependent transition at pH 7 without dissociation of the
      subunits. The data were analyzed in the light of the crystallographic structure
      of the LDH-like L-MalDH from Haloarcula marismortui. This showed that a specific
      loop at the dimer-dimer contact regions in these enzymes controls the tetramer
      formation.

PMID- 11513610
TI  - Insights into the stability of native and partially folded states of ubiquitin:
      effects of cosolvents and denaturants on the thermodynamics of protein folding.
AB  - The thermodynamics of the native<-->A state and native<-->unfolded transitions
      for ubiquitin have been characterized in detail using the denaturants methanol
      and guanidinium chloride (Gdn.HCl) both separately and in combination. Gdn.HCl
      destabilizes the partially folded alcohol-induced A state such that the effects
      of alcoholic solvents on the native<-->unfolded transition can be investigated
      directly via a two-state model. The combined denaturing effects of methanol and
      Gdn.HCl appear to conform to a simple additive model. We show that ubiquitin
      folds and unfolds cooperatively in all cases, forming the same "native" state;
      however, the thermodynamics of the N<-->U transition change dramatically between
      alcoholic and Gdn.HCl solutions, with folding in aqueous methanol associated with
      large negative enthalpy and entropy terms at 298 K with a gradual falloff in
      DeltaC(p) at higher methanol concentrations, as previously reported for the N<-
      >A transition (Woolfson, D. N., Cooper, A., Harding, M. M., Williams, D. H., and
      Evans, P. A. (1993) J. Mol. Biol. 229, 502-511.). Both the N<-->U and the N<-->A
      transitions are enthalpy driven to a similar extent. We conclude that under these
      conditions van der Waals interactions in the packing of the nonpolar protein
      core, which is common to both the N<-->U and the N<-->A transitions, appear to
      drive folding in the absence of entropic effects associated with release of
      ordered solvent (hydrophobic effect). Solvent transfer studies of hydrocarbons
      into alcoholic solvents, with and without Gdn.HCl, are consistent with a large
      enthalpic driving force for burial of a nonpolar surface, with a linear
      dependence of protein stability (DeltaG(N)(<-->)(U)) on cosolvent concentration
      reflected in a similar linear dependence of hydrocarbon solubility. The data
      demonstrate that the hydrophobic effect is not a prerequisite for specific
      stabilization of the native state or the A state and that van der Waals packing
      of the nonpolar core appears to be the dominant factor in stabilization of the
      native state.

PMID- 11513611
TI  - Stabilization of a fibronectin type III domain by the removal of unfavorable
      electrostatic interactions on the protein surface.
AB  - It is generally considered that electrostatic interactions on the protein
      surface, such as ion pairs, contribute little to protein stability, although they
      may play important roles in conformational specificity. We found that the tenth
      fibronectin type III domain of human fibronectin (FNfn10) is more stable at
      acidic pH than neutral pH, with an apparent midpoint of transition near pH 4.
      Determination of pK(a)'s for all the side chain carboxyl groups of Asp and Glu
      residues revealed that Asp 23 and Glu 9 have an upshifted pK(a). These residues
      and Asp 7 form a negatively charged patch on the surface of FNfn10, with Asp 7
      centrally located between Asp 23 and Glu 9, suggesting repulsive electrostatic
      interactions among these residues at neutral pH. Mutant proteins, D7N and D7K, in
      which Asp 7 was replaced with Asn and Lys, respectively, exhibited a modest but
      significant increase in stability at neutral pH, compared to the wild type, and
      they no longer showed pH dependence of stability. The pK(a)'s of Asp 23 and Glu 9
      in these mutant proteins shifted closer to their respective unperturbed values,
      indicating that the unfavorable electrostatic interactions have been reduced in
      the mutant proteins. Interestingly, the wild-type and mutant proteins were all
      stabilized to a similar degree by the addition of 1 M sodium chloride at both
      neutral and acidic pH, suggesting that the repulsive interactions between the
      carboxyl groups cannot be effectively shielded by 1 M sodium chloride. These
      results indicate that repulsive interactions between like charges on the protein
      surface can destabilize a protein, and protein stability can be significantly
      improved by relieving these interactions.

PMID- 11513612
TI  - The C1 domain of protein kinase C as a lipid bilayer surface sensing module.
AB  - The activity of membrane-associated protein kinase C (PKC) is tightly controlled
      by the physical properties of the membrane lipid bilayer, in particular,
      curvature stress, which is induced by bilayer-destabilizing lipid components. An
      important example of this is the weakened lipid headgroup interactions induced by
      phosphatidylethanolamine (PE) and cholesterol. In this work our previous
      observation with a mixed isoform PKC showing a biphasic dependence of activity as
      a function of membrane curvature stress [Slater et al. (1994) J. Biol. Chem. 269,
      4866-4871] was here extended to individual isoforms. The Ca(2+)-dependent
      PKCalpha, PKCbeta, and PKCgamma, along with Ca(2+)-independent PKCdelta, but not
      PKCepsilon or PKCzeta, displayed a biphasic activity as a function of membrane PE
      content. The fluorescence anisotropy of N-(5-dimethylaminonaphthalene-1
      sulfonyl)dioleoylphosphatidylserine (dansyl-PS), which probes the lipid
      environment of PKC, also followed a biphasic profile as a function of PE content
      for full-length PKCalpha, PKCbetaIotaIota, and PKCgamma as did the isolated C1
      domain of PKCalpha. In addition, the rotational correlation time of both PKCalpha
      and PKCdelta C1-domain-associated sapintoxin D, a fluorescent phorbol ester, was
      also a biphasic function of membrane lipid PE content. These results indicate
      that the C1 domain acts as a sensor of the bilayer surface properties and that
      its conformational response to these effects may directly underlie the resultant
      effects on enzyme activity.

PMID- 11513613
TI  - Sites of nucleic acid binding in type I-IV intermediate filament subunit
      proteins.
AB  - A combination of enzymatic and chemical ladder sequencing of photo-cross-linked
      protein-single-stranded oligodeoxyribonucleotide complexes and analysis by MALDI
      TOF mass spectrometry was employed to identify the amino acid residues
      responsible for the stable binding of nucleic acids in several intermediate
      filament (IF) subunit proteins. The IF proteins studied included the type I and
      type II cytokeratins K8, K18, and K19; the type III proteins desmin, glial
      fibrillary acidic protein (GFAP), peripherin, and vimentin; and the type IV
      neurofilament triplet protein L (NF-L). The site of nucleic acid binding was
      localized to the non-alpha-helical, amino-terminal head domain of all of the IF
      proteins tested. GFAP, which has the shortest head domain of the proteins tested,
      cross-linked via only two amino acid residues. One of these residues was located
      within a conserved nonapeptide domain that has been shown to be required for
      filament formation. One or more cross-linked residues were found in a similar
      location in the other proteins studied. The major binding site for nucleic acids
      for most of the proteins appears to be localized within the middle of the head
      domain. The two exceptions to this generalization are GFAP, which lacks these
      residues, and NF-L, in which a large number of cross-linked residues were found
      scattered throughout the first half of the head domain. Control experiments were
      also done with two bacteriophage ssDNA-binding proteins, as well as actin and
      tubulin. The single sites of cross-linkage observed with the bacteriophage
      proteins, Phe(183) for the T4 gene 32 protein and Phe(73) for the M13 gene 5
      protein, were in good agreement with literature data. Actin and tubulin could not
      be cross-linked to the oligonucleotide. Aside from the insight into the
      biological activity of IF proteins that these data provide, they also demonstrate
      that this analytical method can be employed to study a variety of protein-nucleic
      acid interactions.

PMID- 11513614
TI  - Mutations of arginine 64 within the putative Ca(2+)-binding lumenal interhelical
      a-b loop of the photosystem II D1 protein disrupt binding of the manganese
      stabilizing protein and cytochrome c(550) in Synechocystis sp. PCC6803.
AB  - Mutations D1-R64E, D1-R64Q, and D1-R64V in the putative calcium-binding lumenal
      interhelical a-b loop of the photosystem II (PSII) D1 protein were characterized
      in terms of impact on growth, extrinsic protein binding, photoactivation, and
      properties of the H(2)O-oxidation complex. The D1-R64E charge reversal mutation
      greatly weakened the binding of the extrinsic manganese-stabilizing protein (MSP)
      and, to a considerably lesser extent, weakened the binding of cytochrome c(550)
      (c550). Both D1-R64Q and D1-R64E exhibited an increased requirement for Ca(2+) in
      the cell growth medium. Bare platinum electrode measurements of O(2)-evolving
      membranes showed a retarded appearance of O(2) following single turn-over
      flashes, especially in the case of the D1-R64E mutant. The D1-R64E mutant also
      had a pronounced tendency to lose O(2) evolution activity in the dark and
      exhibited an increased relative quantum yield of photoactivation, which are
      characteristics shared by mutants that lack extrinsic proteins. S(2) and S(3)
      decay measurements in the isolated membranes indicate that D1-R64E and D1-R64Q
      have faster decays of these higher S-states as compared to the wild-type.
      However, fluorescence decay in the presence of DCMU, which monitors primarily
      Q(A)(-) charge recombination with PSII donors, showed somewhat slower decays.
      Taken together, the fluorescence and S-state decay indicate that the midpoint of
      either Q(B)(-) has been modified to be more negative in the mutants or that a
      recombination path presumably involving either Q(B)(-) or Y(D) has become
      kinetically more accessible.

PMID- 11513615
TI  - Cationic ascorbate peroxidase isoenzyme II from tea: structural insights into the
      heme pocket of a unique hybrid peroxidase.
AB  - The novel class III ascorbate peroxidase isoenzyme II from tea leaves (TcAPXII),
      with an unusually high specific ascorbate peroxidase activity associated with
      stress response, has been characterized by resonance Raman (RR), electronic
      absorption, and Fourier transform infrared (FT-IR) spectroscopies. Ferric and
      ferrous forms and the complexes with fluoride, cyanide, and CO have been studied
      at various pH values. The overall blue shift of the electronic absorption
      spectrum, the high RR frequencies of the core size marker bands, similar to those
      of 6-coordinate low-spin heme, and the complex RR spectrum in the low-frequency
      region of ferric TcAPXII indicate that this protein contains an unusual 5
      coordinate quantum mechanically mixed-spin heme. The spectra of both the fluoride
      and the CO adducts suggest that these exogenous ligands are strongly hydrogen
      bonded with a residue that appears to be unique to this peroxidase. Electronic
      absorption spectra also emphasize structural differences between the
      benzhydroxamic acid binding sites of TcAPXII and horseradish peroxidases (HRPC).
      It is concluded that TcAPXII is a paradigm peroxidase since it is the first
      example of a hybrid enzyme that combines spectroscopic signatures, structural
      elements, and substrate specificities previously reported only for distinct class
      I and class III peroxidases.

PMID- 11513616
TI  - Transient-state and steady-state kinetic studies of the mechanism of NADH
      dependent aldehyde reduction catalyzed by xylose reductase from the yeast Candida
      tenuis.
AB  - Microbial xylose reductase, a representative aldo-keto reductase of primary sugar
      metabolism, catalyzes the NAD(P)H-dependent reduction of D-xylose with a turnover
      number approximately 100 times that of human aldose reductase for the same
      reaction. To determine the mechanistic basis for that physiologically relevant
      difference and pinpoint features that are unique to the microbial enzyme among
      other aldo/keto reductases, we carried out stopped-flow studies with wild-type
      xylose reductase from the yeast Candida tenuis. Analysis of transient kinetic
      data for binding of NAD(+) and NADH, and reduction of D-xylose and oxidation of
      xylitol at pH 7.0 and 25 degrees C provided estimates of rate constants for the
      following mechanism: E + NADH right arrow over left arrow E.NADH right arrow over
      left arrow E.NADH + D-xylose right arrow over left arrow E.NADH.D-xylose right
      arrow over left arrow E.NAD(+).xylitol right arrow over left arrow E.NAD(+) right
      arrow over left arrow E.NAD(+) right arrow over left arrow E + NAD(+). The net
      rate constant of dissociation of NAD(+) is approximately 90% rate limiting for
      k(cat) of D-xylose reduction. It is controlled by the conformational change which
      precedes nucleotide release and whose rate constant of 40 s(-)(1) is 200 times
      that of completely rate-limiting E.NADP(+) --> E.NADP(+) step in aldehyde
      reduction catalyzed by human aldose reductase [Grimshaw, C. E., et al. (1995)
      Biochemistry 34, 14356-14365]. Hydride transfer from NADH occurs with a rate
      constant of approximately 170 s(-1). In reverse reaction, the E.NADH --> E.NADH
      step takes place with a rate constant of 15 s(-1), and the rate constant of
      ternary-complex interconversion (3.8 s(-1)) largely determines xylitol turnover
      (0.9 s(-1)). The bound-state equilibrium constant for C. tenuis xylose reductase
      is estimated to be approximately 45 (=170/3.8), thus greatly favoring aldehyde
      reduction. Formation of productive complexes, E.NAD(+) and E.NADH, leads to a 7-
      and 9-fold decrease of dissociation constants of initial binary complexes,
      respectively, demonstrating that 12-fold differential binding of NADH (K(i) = 16
      microM) vs NAD(+) (K(i) = 195 microM) chiefly reflects difference in stabilities
      of E.NADH and E.NAD(+). Primary deuterium isotope effects on k(cat) and
      k(cat)/K(xylose) were, respectively, 1.55 +/- 0.09 and 2.09 +/- 0.31 in H(2)O,
      and 1.26 +/- 0.06 and 1.58 +/- 0.17 in D(2)O. No deuterium solvent isotope effect
      on k(cat)/K(xylose) was observed. When deuteration of coenzyme selectively slowed
      the hydride transfer step, (D)()2(O)(k(cat)/K(xylose)) was inverse (0.89 +/-
      0.14). The isotope effect data suggest a chemical mechanism of carbonyl reduction
      by xylose reductase in which transfer of hydride ion is a partially rate-limiting
      step and precedes the proton-transfer step.

PMID- 11513617
TI  - Sequence requirements of the ATP-binding site within the C-terminal nucleotide
      binding domain of mouse P-glycoprotein: structure-activity relationships for
      flavonoid binding.
AB  - Sequence requirements of the ATP-binding site within the C-terminal nucleotide
      binding domain (NBD2) of mouse P-glycoprotein were investigated by using two
      recombinantly expressed soluble proteins of different lengths and photoactive ATP
      analogues, 8-azidoadenosine triphosphate (8N(3)-ATP) and 2',3',4'-O-(2,4,6
      trinitrophenyl)-8-azidoadenosine triphosphate (TNP-8N(3)-ATP). The two proteins,
      Thr(1044)-Thr(1224) (NBD2(short)) and Lys(1025)-Ser(1276) (NBD2(long)), both
      incorporated the four consensus sequences of ABC (ATP-binding cassette)
      transporters, Walker A and B motifs, the Q-loop, and the ABC signature, while
      differing in N-terminal and C-terminal extensions. Radioactive photolabeling of
      both proteins was characterized by hyperbolic dependence on nucleotide
      concentration and high-affinity binding with K(0.5)(8N(3)-ATP) = 36-37 microM and
      K(0.5)(TNP-8N(3)-ATP) = 0.8-2.6 microM and was maximal at acidic pH.
      Photolabeling was strongly inhibited by TNP-ATP (K(D) = 0.1-5 microM) and ATP
      (K(D) = 0.5-2.7 mM). Since flavonoids display bifunctional interactions at the
      ATP-binding site and a vicinal steroid-interacting hydrophobic sequence [Conseil,
      G., Baubichon-Cortay, H., Dayan, G., Jault, J.-M., Barron, D., and Di Pietro, A.
      (1998) Proc. Natl. Acad. Sci. U.S.A. 95, 9831-9836], a series of 30 flavonoids
      from different classes were investigated for structure-activity relationships
      toward binding to the ATP site, monitored by protection against photolabeling.
      The 3-OH and aromaticity of conjugated rings A and C appeared important, whereas
      opening of ring C abolished the binding in all but one case. It can be concluded
      that the benzopyrone portion of the flavonoids binds at the adenyl site and the
      phenyl ring B at the ribosyl site. The Walker A and B motifs, intervening
      sequences, and small segments on both sides are sufficient to constitute the ATP
      site.

PMID- 11513618
TI  - The srhSR gene pair from Staphylococcus aureus: genomic and proteomic approaches
      to the identification and characterization of gene function.
AB  - Systematic analysis of the entire two-component signal transduction system
      (TCSTS) gene complement of Staphylococcus aureus revealed the presence of a
      putative TCSTS (designated SrhSR) which shares considerable homology with the
      ResDE His-Asp phospho-relay pair of Bacillus subtilis. Disruption of the srhSR
      gene pair resulted in a dramatic reduction in growth of the srhSR mutant, when
      cultured under anaerobic conditions, and a 3-log attenuation in growth when
      analyzed in the murine pyelonephritis model. To further understand the role of
      SrhSR, differential display two-dimensional gel electrophoresis was used to
      analyze the cell-free extracts derived from the srhSR mutant and the
      corresponding wild type. Proteins shown to be differentially regulated were
      identified by mass spectrometry in combination with protein database searching.
      An srhSR deletion led to changes in the expression of proteins involved in energy
      metabolism and other metabolic processes including arginine catabolism, xanthine
      catabolism, and cell morphology. The impaired growth of the mutant under
      anaerobic conditions and the dramatic changes in proteins involved in energy
      metabolism shed light on the mechanisms used by S. aureus to grow anaerobically
      and indicate that the staphylococcal SrhSR system plays an important role in the
      regulation of energy transduction in response to changes in oxygen availability.
      The combination of proteomics, bio-informatics, and microbial genetics employed
      here represents a powerful set of techniques which can be applied to the study of
      bacterial gene function.

PMID- 11513619
TI  - The 4,4'-dipyridyl disulfide-induced formation of GroEL monomers is cooperative
      and leads to increased hydrophobic exposure.
AB  - The molecular chaperone, GroEL, is completely disassembled into monomers by the
      addition of 4,4'-dipyridyl disulfide. The dissociation leads to monomers in a
      kinetically controlled process. The additions of functional ligands of GroEL such
      as Mg(2+) or adenine nucleotides produced differences in the observed rates, but
      at the end of the kinetics, the dissociation was complete. In addition to the
      information obtained from native gels, the fluorescent probe bis-ANS was utilized
      to follow the monomer formation. The results demonstrate that the formation of
      monomers was associated with the exposure of hydrophobic surfaces. This
      assessment was possible without the use of added chaotropes, such as urea, to
      dissociate GroEL. Dissociation kinetics were also followed by light scattering.
      The kinetics of dissociation of the 14mer are cooperative with respect to the
      concentration of 4,4'-DPDS. Thermodynamic parameters for the kinetic process gave
      a free energy of activation (DeltaG) of 19.3 +/- 1.2 kcal mol(-1), which was
      decomposed to an enthalpy of activation (DeltaH) of 19.30 +/- 1.2 kcal mol(-1)
      and an entropy of activation (DeltaS) of -8.2 +/- 3.9 cal mol(-1) K(-1). We
      conclude that the dissociation of GroEL observed in this investigation is an
      enthalpy-controlled process.

PMID- 11513620
TI  - Polyphenolic content in olive oil waste waters and related olive samples.
AB  - The production of olive oil yields a considerable amount of waste water, which is
      a powerful pollutant and is currently discarded. Polyphenols and other natural
      antioxidants, extracted from olives during oil extraction process, partially end
      up in the waste waters. Experimental and commercial olive oil waste waters from
      four Mediterranean countries were analyzed for a possible recovering of these
      biologically interesting constituents. Identification and quantitation of the
      main polyphenols were carried out by applying HPLC-DAD and HPLC-MS methods.
      Representative samples of ripe olives were also analyzed at the same time to
      correlate, if possible, their polyphenolic profiles with those of the
      corresponding olive oil waste waters. The results demonstrate that Italian
      commercial olive oil waste waters were the richest in total polyphenolic
      compounds with amounts between 150 and 400 mg/100 mL of waste waters. These raw,
      as yet unused, matrices could represent an interesting and alternative source of
      biologically active polyphenols.

PMID- 11513621
TI  - Separation, identification, quantification, and method validation of anthocyanins
      in botanical supplement raw materials by HPLC and HPLC-MS.
AB  - A method has been established and validated for identification and quantification
      of individual, as well as total, anthocyanins by HPLC and LC/ES-MS in botanical
      raw materials used in the herbal supplement industry. The anthocyanins were
      separated and identified on the basis of their respective M(+) (cation) using
      LC/ES-MS. Separated anthocyanins were individually calculated against one
      commercially available anthocyanin external standard (cyanidin-3-glucoside
      chloride) and expressed as its equivalents. Amounts of each anthocyanin
      calculated as external standard equivalent were then multiplied by a molecular
      weight correction factor to afford their specific quantities. Experimental
      procedures and use of a molecular-weight correction factors are substantiated and
      validated using Balaton tart cherry and elderberry as templates. Cyanidin-3
      glucoside chloride has been widely used in the botanical industry to calculate
      total anthocyanins. In our studies on tart cherry and elderberry, its use as
      external standard followed by use of molecular-weight correction factors should
      provide relatively accurate results for total anthocyanins, because of the
      presence of cyanidin as their major anthocyanidin backbone. The method proposed
      here is simple and has a direct sample preparation procedure without any solid
      phase extraction. It enables selection and use of commercially available
      anthocyanins as external standards for quantification of specific anthocyanins in
      the sample matrix irrespective of their commercial availability as analytical
      standards. It can be used as a template and applied for similar quantification in
      several anthocyanin-containing raw materials for routine quality control
      procedures, thus providing consistency in analytical testing of botanical raw
      materials used for manufacturing efficacious and true-to-the-label nutritional
      supplements.

PMID- 11513622
TI  - Reaction between albumen and 3,3',5,5'-tetramethylbenzidine as a method to
      evaluate egg freshness.
AB  - The 3,3',5,5'-tetramethylbenzidine colorimetric test is proposed as a method for
      the evaluation of shell egg freshness. A simplification of the original method
      was tested on albumen, and the modified method was used to study the development
      of albumen-tetramethylbenzidine reaction in eggs stored at three temperatures for
      different times. The stability of the reagent solution and the repeatability of
      the analytical method were also studied. The reaction mechanism showed the
      predominant role of iron ions on the colorimetric response, and the secondary
      role of copper ions added to the reaction mix in order to enhance the response.
      The response coefficient of variation, due to the natural variability in eggs
      laid by hens of two breeds and different ages, was 10.3%, which is similar to the
      value obtained for furosine, but lower than those previously observed for other
      egg freshness indices such as Haugh Unit and air-cell height.

PMID- 11513623
TI  - NMR analysis of the iron ligand ethylenediaminedi(o-hydroxyphenyl)acetic acid
      (EDDHA) employed in fertilizers.
AB  - The exceptional efficiency of the iron chelate of ethylenediaminedi(o
      hydroxyphenyl)acetic acid (o,o-EDDHA) in correcting iron chlorosis in plants and
      the medical applications of various metallic chelates of this compound have long
      been recognized. As commercial preparations of o,o-EDDHA usually contain
      impurities, a method for their detection is proposed. By using one- and two
      dimensional nuclear magnetic resonance two impurities were identified. The
      structure of one of these compounds was assigned to an isomer of EDDHA containing
      at least one p-hydroxyphenyl moiety. The structure of the other impurity was
      tentatively assigned to a byproduct of the EDDHA synthesis: 2,6
      di[CH(COOH)NHCH(2)CH(2)NHCH(COOH)Ar]phenol (Ar = hydroxyphenyl). Both compounds
      were also detected in the EDDHA extracted from a commercial iron fertilizer.

PMID- 11513624
TI  - A headspace solid-phase microextraction method for the determination of some
      secondary compounds of Brazilian sugar cane spirits by gas chromatography.
AB  - A headspace solid-phase microextraction (SPME) method was developed for the
      determination of secondary compounds from Brazilian sugar cane spirits, or
      cachaca, by GC-FID. An SPME holder with an 85 microm polyacrylate coating was
      utilized. The novel method is compared with an optimized method: liquid-liquid
      extraction (LLE). Both methods showed good linearity, but the repeatability for
      analyses done with the SPME technique (%RSD = 1.8-3.9) was better than for those
      done with LLE (%RSD = 10.3-11.7). The concentrations of the analytes obtained in
      the analysis of 12 cachaca samples with the SPME technique were higher than those
      obtained with LLE. In the SPME method the extraction wastes are smaller. Cachaca
      samples were qualitatively analyzed for GC-MS.

PMID- 11513625
TI  - Analysis of organophosphorus pesticides in honeybee by liquid chromatography
      atmospheric pressure chemical ionization-mass spectrometry.
AB  - Pesticides applied in extended agricultural fields may be controlled by means of
      bioindicators, such as honeybees, in which are the pesticides bioaccumulate.
      Liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry
      (LC-APCI-MS) experiments with positive (PI) and negative (NI) ion modes were
      optimized for the analysis of 22 organophosphorus pesticides in honeybee samples.
      The extraction required 3 g of sample, which was extracted with acetone. The
      extract was purified with coagulating solution and reextracted with Cl(2)CH(2).
      Pesticides studied could be detected by both ionization modes except for
      parathion, parathion-methyl, and bromophos, which did not give signals in PI
      mode, and triazophos, which was not detected in NI mode. Fragmentation voltage
      and vaporizer temperature were optimized to achieve the highest sensitivity. The
      spectra profile of each pesticide in PI mode showed the [M + H](+) ion as the
      main signal, whereas in NI mode only fragment ions were shown. The detection
      limit obtained in selected ion monitoring mode ranged from 1 to 15 microg kg(-1).
      The average recoveries from spiked honeybees at various concentration levels (0.5
      5 mg kg(-1)) exceeded 65% with relative standard deviations of 4-15%. The method
      was applied to real samples, in which residues of coumaphos and dimethoate were
      detected.

PMID- 11513626
TI  - Determination of daminozide residues in apple pulp using HPLC-DAD-UV.
AB  - This paper reports an HPLC-UV method to determine daminozide residues in apple
      pulps adopting the recently introduced EU limit of 0.01 mg/kg for baby food
      preparation (Commission Directive 1999/39/CE). The method is based on alkaline
      hydrolysis of daminozide to N',N'-dimethylhydrazine (UDMH), which is recovered by
      distillation and subsequently derivatizated with salicyl aldehyde to salicyl
      aldehyde-N,N-dimethylhydrazone under strongly basic conditions. The resulting
      solution was cleaned up with Extrelut 20 NT and dichloromethane as eluent, then
      analyzed by HPLC with a C18 column and a mobile phase programmed from 50:50
      AcCN/H(2)O to 100% AcCN. The salicyl aldehyde-N,N-dimethylhydrazone was
      selectively detected through two diagnostic UV absorption maxima at 295 and 325
      nm, which have strong molar absorbivities. Recoveries of daminozide at 0.01 mg/kg
      were above 80%. The limits of detection (LODs) of salicyl aldehyde-N,N
      dimethylhydrazone expressed as daminozide concentration were 100 pg/microL at 295
      nm and 150 pg/microL at 325 nm, and the limits of quantitation (LOQs) of
      daminozide were 0.0013 mg/kg at 295 nm and 0.0022 mg/kg at 325 nm.

PMID- 11513627
TI  - Rapid HPLC screening of jasmonate-induced increases in tobacco alkaloids,
      phenolics, and diterpene glycosides in Nicotiana attenuata.
AB  - A rapid, HPLC-based screening procedure for the main classes of secondary
      metabolites in Nicotiana attenuata leaves (alkaloids, phenolics, and diterpene
      glycosides) is reported. In a single step, leaves are extracted in aqueous
      acidified (0.5% acetic acid) methanol, and the extracted compounds are separated
      by reversed-phase HPLC with an acidic water/acetonitrile gradient in <30 min. The
      utility of the method in quantifying changes in the secondary metabolites after
      methyl jasmonate treatment of the plants, a treatment known to elicit resistance
      to herbivores in nature, is illustrated. Methyl jasmonate treatment elicited
      dramatic increases in some secondary metabolites (caffeoylputrescine, nicotine,
      and diterpene glycosides increased 12.5-, 1.4-, and 1.9-fold, respectively) but
      left others, such as rutin, unchanged. Such broad-based analytical screens will
      help characterize environmental and genetic changes in secondary metabolite
      profiles.

PMID- 11513628
TI  - Screening spring wheat for midge resistance in relation to ferulic acid content.
AB  - The concentration of ferulic acid (FA), the major phenolic acid in the wheat
      kernel, was found to differ significantly in the mature grain of six wheat
      cultivars known to have a range of tolerance to the orange wheat blossom midge
      (Sitodiplosis mosellana). Differences in FA content were correlated with floret
      infestation level of the cultivars. The wheat cultivars ranked similarly in FA
      content at the four locations where they were tested, despite a significant
      effect of environment. Ferulic acid was synthesized mainly during the early
      stages of grain filling but at different rates among cultivars. Ferulic acid was
      concentrated primarily in the shorts and bran fractions in an insoluble-bound
      form. A high correlation was obtained between FA contents as determined by GLC,
      fluorometry, UV, and colorimetry. The colorimetric procedure was modified as a
      qualitative, simple, and rapid test for identifying midge-resistant wheat and
      evaluated in several field trials. The method should provide a rapid tool in the
      preliminary screening of experimental lines in the development of midge-resistant
      wheat cultivars.

PMID- 11513629
TI  - Development of a new methanethiol quantification method using ethanethiol as an
      internal standard.
AB  - Development of a new method to quantify methanethiol in which ethanethiol was
      employed as an internal standard is reported. Recovery yields for methanethiol
      from an aqueous model system and a soy protein concentrate (SPC) aqueous slurry
      determined with this method ranged from 97 to 107% and from 103 to 121%,
      respectively. The methanethiol content of two commercial SPCs and two commercial
      soy protein isolate (SPI) samples, on a dry basis, ranged from 835 to 1190 times
      greater than the odor threshold for methanethiol. Relative standard deviations
      for quantifying methanethiol with the method from these samples were <5%,
      indicating its good reproducibility in quantifying methanethiol from soy protein
      products. Also investigated in the current study was the feasibility of using
      5',5-dithiobis(2-nitrobenzoic acid) (DTNB, Ellman's reagent) to determine the
      concentration of methanethiol in the aqueous solutions used to prepare the
      standard curve for quantifying methanethiol from soy protein products. The
      concentrations of methanethiol obtained from Ellman's reagent method were
      comparable with those from a weighing method and theoretical calculation.

PMID- 11513630
TI  - Quantitative (13)C NMR analysis of lignins with internal standards.
AB  - Novel protocols for acquiring quantitative (13)C NMR spectra of lignins have been
      developed using the internal reference compounds 1,3,5-trioxane and
      pentafluorobenzene. Trioxane offers a convenient internal standard for collecting
      inverse gated proton decoupled (13)C NMR spectra for lignins, whereas
      pentafluorobenzene can be used to provide information on the amount of methine
      carbon using the DEPT experiment. In each case, the internal reference compounds
      provide single, un-overlapped sharp signals in the middle of the spectral region,
      permitting facile integration. These integrals could be used to determine the
      amounts of different structural features of lignins, expressed in absolute units
      of millimoles per gram. The optimum parameters for these experiments were
      validated for a variety of spectrometer platforms, and standard errors were
      determined for different spectral areas using lignin model compounds and
      "standard" lignins. In addition, the data derived for the International Round
      Robin "standard" lignins showed good agreement with the data from quantitative
      (31)P NMR spectroscopy and published data, obtained by independent laboratories
      using independent methods of analysis.

PMID- 11513631
TI  - Improved high-performance liquid chromatography method to determine theobromine
      and caffeine in cocoa and cocoa products.
AB  - At present, the commonly used HPLC method for the analysis of caffeine and
      theobromine contents in aqueous cocoa extracts employs direct application of the
      extracts on the column. This practice gradually reduces the efficiency of the
      column and shortens its life. Also, this method gives inflated values due to
      interfering substances and difficulty in achieving baseline resolution. In the
      improved method, the interfering cocoa pigments are effectively removed by
      passing the aqueous extract through a Sep-pak C(18) cartridge. Subsequent
      injection on a C(18) reverse-phase column employing acetonitrile and water
      (20:80) as the mobile phase reduces the analysis time without affecting either
      resolution of the peak or the accuracy of caffeine and theobromine determination
      or achieving baseline resolution. Therefore, this method is ideally suited for
      rapid routine analysis of cocoa and its products.

PMID- 11513632
TI  - Rapid spectrophotometric determination of red and yellow isochromic carotenoid
      fractions in paprika and red pepper oleoresins.
AB  - A rapid method has been developed for the determination of the red (R) and yellow
      (Y) isochromic carotenoid pigments fractions in paprika and oleoresins, based on
      UV-visible spectrophotometric measurement at two characteristic wavelengths and
      application of the Lambert-Beer law for multicomponent mixtures. The wavelengths
      472 and 508 nm were selected as the most appropriate for simultaneous
      quantification of these fractions in the acetone extract of pigments.
      Experimental determination of the specific absorption coefficients (epsilon) for
      the two pigment fractions (R, Y) at 472 and 508 nm yielded equations to calculate
      the concentration of the two fractions, the total pigment content, and the ratio
      between the two fractions. The error in the determination of the isochromic
      fractions by the proposed spectrophotometric method was <5% when the results were
      compared with those obtained by HPLC analysis. The method can be applied to the
      direct extract of pigments, thereby avoiding saponification and minimizing errors
      from pigment degradation and sample manipulation as well as shortening the time
      of analysis (5 min in the case of oleoresins).

PMID- 11513633
TI  - Determination of 4,4'-dinitrocarbanilide (DNC), the active component of the
      antifertility agent nicarbazin, in chicken, duck, and goose plasma.
AB  - 4,4'-Dinitrocarbanilide (DNC) was extracted from chicken, duck, and goose plasma
      and isolated by reversed-phase high-performance liquid chromatography. DNC was
      detected by ultraviolet absorbance at 347 nm and quantified by comparison to a
      calibration standard. Recovery data were determined by analyzing DNC-fortified
      control plasma. The mean recovery of DNC in fortified chicken plasma samples was
      99.7 +/- 1.9% for 0.18 and 9.1 ppm DNC, and in fortified duck and goose plasma
      samples was 99.5 +/- 4.9% and 101.4 +/- 4.5%, respectively, for 0.18, 9.1, and 18
      ppm DNC.

PMID- 11513634
TI  - Rapid isolation and purification of 1-cyano-2-hydroxy-3-butene (crambene) from
      Crambe abyssinica seed meal using immiscible solvent extraction and high
      performance liquid chromatography.
AB  - 1-Cyano-2-hydroxy-3-butene (crambene) is a nitrile found in cruciferous
      vegetables that causes significant upregulation of quinone reductase and
      glutathione S-transferases in vivo and in vitro, making it a likely candidate as
      a cancer chemopreventive compound. To investigate further the putative
      anticarcinogenic mechanisms of crambene, a compound of the highest possible
      purity is vital. Therefore, a rapid and effective method of purification of
      crambene is necessary to continue studies of its beneficial health effects. A
      rapid method to isolate and purify natural crambene from either Crambe abyssinica
      (crambe) seed or commercially processed crambe seed meal was developed using
      immiscible solvent extraction followed by high-performance liquid chromatography.
      Use of this methodology eliminated the need for time-consuming and relatively
      inefficient column chromatography, improved extraction efficiency, and resulted
      in higher purity than previously used methodologies. Elimination of trace amounts
      of fatty acid residues, unachievable with previous methodologies, also was
      accomplished.

PMID- 11513635
TI  - Influence of CaCl(2) on the foliar biomass and quality of tobacco leaves.
AB  - The aim of the present work was to determine the influence of different CaCl(2)
      dosages on foliar biomass and quality of tobacco plants (Nicotiana tabacum L.
      var. Tennesse 86). Plants were grown under controlled conditions and submitted to
      regular fertilization with macro- and micronutrients. The CaCl(2) was applied to
      the nutrient solution at 1.25 mM (T1), 2.5 mM (T2), and 5 mM (T3). The results
      indicated that, under the experimental conditions of this work, the application
      of 1.25 mM of CaCl(2) favored the growth and development of the leaves, this
      leading to improved biomass production in tobacco leaves. The increase in foliar
      biomass in treatment T1 could largely be a result of the stimulation of NO(3)(-)
      assimilation. However, this situation has negative consequences for tobacco
      quality, given that the T1 treatment augmented the NO(3)(-) concentration and the
      foliar concentration of nicotine (both effects being harmful for human
      consumption) and decreased the concentration of reducing sugars in leaves of
      tobacco plants compared with those of T2 and T3. Finally, a close and directly
      proportional relationship was found in our experiment between the parameters of
      foliar-biomass production, total N concentration, chlorophyll concentration, and
      decline in quality.

PMID- 11513636
TI  - Activity and concentration of polyphenolic antioxidants in apple: effect of
      cultivar, harvest year, and storage conditions.
AB  - Consumers' increasing interest in the relationship between diet and health is a
      sign for food producers to pay more attention to potential health-protecting
      compounds in new product development and food processing. From a production chain
      perspective the choice of the raw material that is used is important for the
      health-protecting potential of the end product. Four apple cultivars (Jonagold,
      Golden Delicious, Cox's Orange, and Elstar), which can be used as fresh apples or
      in processed apple products, were compared with regard to flavonol, catechins,
      phloridzin, and chlorogenic acid concentrations and antioxidant activity.
      Jonagold apples possessed the highest flavonoid concentration and the highest
      antioxidant activity. To study seasonal differences, apples from three different
      harvest years were analyzed, but in three cultivars no effect on flavonoid
      concentration and antioxidant activity was observed. Long-term storage, both at
      refrigerator temperature and under controlled atmosphere conditions, was found
      not to influence flavonoid concentration or antioxidant activity.

PMID- 11513637
TI  - Peroxynitrite scavenging and cytoprotective activity of 2,3,6-tribromo-4,5
      dihydroxybenzyl methyl ether from the marine alga Symphyocladia latiuscula.
AB  - Peroxynitrite (ONOO(-)), formed from the reaction of superoxide (O(2)*(-)) and
      nitric oxide (*NO), is a cytotoxic species that can oxidize several cellular
      components such as proteins, lipids, and DNA. It has been implicated in diseases
      such as Alzheimer's disease, rheumatoid arthritis, cancer, and atherosclerosis.
      Due to the lack of endogenous enzymes responsible for ONOO(-) inactivation,
      developing a specific ONOO(-) scavenger is of considerable importance. The aim of
      this study was to evaluate the ability of marine natural products to scavenge
      ONOO(-) and to protect cells against ONOO(-). Methanolic extracts of 17 marine
      alga were tested for their ONOO(-) scavenging activity. Among them, Symphyocladia
      latiuscula showed the potent scavenging activity. CH(2)CH(2) fraction was
      partitioned with CH(2)CH(2) following n-hexanal extraction from the methanol
      extract of S. latiuscula. It was highly effective for ONOO(-) scavenging
      activity. Further analysis of the active fractionated extract identified 2,3,6
      tribromo-4,5-dihydroxybenzyl methyl ether (TDB) as a potent ONOO(-) scavenger.
      The data demonstrated that TDB led to decreased ONOO(-)-mediated nitration of
      tyrosine through electron donation. TDB showed significant inhibition on
      nitration of bovine serum albumin and low-density lipoprotein by ONOO(-) in a
      dose-dependent manner. It also provided cytoprotection from cell damage induced
      by ONOO(-). TDB can be developed as an effective peroxynitrite scavenger for the
      prevention of the involved diseases.

PMID- 11513638
TI  - A rapeseed-specific gene, acetyl-CoA carboxylase, can be used as a reference for
      qualitative and real-time quantitative PCR detection of transgenes from mixed
      food samples.
AB  - Polymerase chain reaction (PCR) methods are very useful techniques for the
      detection and quantification of genetically modified organisms (GMOs) in food
      samples. These methods rely on the amplification of transgenic sequences and
      quantification of the transgenic DNA by comparison to an amplified reference
      gene. Reported here is the development of specific primers for the rapeseed
      (Brassica napus) BnACCg8 gene and PCR cycling conditions suitable for the use of
      this sequence as an endogenous reference gene in both qualitative and
      quantitative PCR assays. Both methods were assayed with 20 different rapeseed
      varieties, and identical amplification products were obtained with all of them.
      No amplification products were observed when DNA samples from other Brassica
      species, Arabidopsis thaliana, maize, and soybean were used as templates, which
      demonstrates that this system is specific for rapeseed. In real-time quantitative
      PCR analysis, the detection limit was as low as 1.25 pg of DNA, which indicates
      that this method is suitable for use in processed food samples which contain very
      low copies of target DNA.

PMID- 11513639
TI  - Synthesis of ligand-specific phage-display ScFv against the herbicide picloram by
      direct cloning from hyperimmunized mouse.
AB  - Immunoglobulin genes were directly isolated from the splenocytes of a BALB/C
      mouse hyperimmunized with the auxinic herbicide picloram conjugated to bovine
      serum albumin. Variable light and heavy domain DNA were joined to produce single
      chain Fv (scFv) DNA, which was cloned into phage vector fd-tet-GIIID to display
      multiple copies of scFv on the filamentous phage minor coat protein gIIIp. The
      phage-display scFv library (10(4) clones) was selected against picloram
      conjugated to ovalbumin. After five rounds of panning, individual clones were
      analyzed. ScFv with different affinities to picloram (IC(50) values ranging from
      20 ppb to 10 ppm) were detected in the final enriched pool. The increased avidity
      of the phage vector enhanced the selection (i.e., panning) of multiple picloram
      specific recombinant antibodies. Stringent selection was required to isolate the
      clones with the highest affinity. Nucleotide sequence analysis of six isolated
      clones revealed that all of the V(L) belonged to the V kappa 9A family joined to
      J kappa 2 segments. All of the V(H) belonged to the V(H)()7183 family and joined
      to two different J segments (i.e., J(H)()2 or J(H)()4). Different from the immune
      response to large molecular weight molecules (MW > 10,000 Da), which requires
      both VDJ segment rearrangement and somatic hypermutations, production of high
      affinity antibodies to picloram, a small ligand having a formula weight of 241.5
      Da, predominantly requires somatic hypermutations.

PMID- 11513640
TI  - Increase in lipid content in potato tubers modified by 14-3-3 gene
      overexpression.
AB  - Recently, transgenic potato plants were created with overexpression of the 14-3-3
      protein derived from Cucurbita pepo. Detailed analysis of those plants suggested
      that the function of the isolated 14-3-3 isoform is in the control of
      carbohydrate and lipid metabolism in the plants. 14-3-3 protein overexpression
      gave rise to an increase in soluble sugar and catecholamine contents in both
      leaves and tubers. It is proposed that 14-3-3 protein affects carbohydrate
      metabolism in potato plants via regulation of catecholamine synthesis.
      Furthermore, genetically modified potato tubers with 14-3-3 protein
      overexpression showed changes in lipid content and composition. The transgenic
      potato tubers contained 69% more total fat compared to the wild-type plant.
      Separation of tuber lipids into polar and nonpolar fractions revealed that the
      transgenic potato tubers contained almost 3 times more nonpolar lipids than the
      control. Analysis of fatty acid composition, conducted by the means of gas
      chromatography, showed that linoleic acid was the main fatty acid present in the
      tubers of both modified and control potato plants. In the nonpolar fraction of
      the fat of the transgenic tubers the unsaturated fatty acids exhibited a higher
      participation in the sum of all fatty acids.

PMID- 11513641
TI  - Efficiency of enzymatic and other alternative clarification and fining treatments
      on turbidity and haze in cherry juice.
AB  - Several alternative strategies were examined for improving conventional juice
      fining procedures for cherry juice clarification and fining in laboratory-scale
      experiments: Centrifugation of freshly pressed juice from 1000g to 35,000g
      induced decreased turbidity according to a steep, negative power function.
      Individual and interactive effects on turbidity and haze formation in
      precentrifuged and uncentrifuged cherry juice of treatments with pectinase, acid
      protease, bromelain, gallic acid, and gelatin-silica sol were investigated in a
      factorial experimental design with 32 different parameter combinations. Gelatin
      silica sol consistently had the best effect on juice clarity. Centrifugation of
      cherry juice (10,000g for 15 min) prior to clarification treatment significantly
      improved juice clarity and diminished the rate of haze formation during cold
      storage of juice. Both treatment of precentrifuged cherry juice with Novozym 89L
      protease and co-addition of pectinase and gallic acid improved cherry juice
      clarity and diminished haze levels. None of the alternative treatments produced
      the unwieldy colloids notorious to gelatin-silica sol treatment. The data suggest
      that several alternative clarification strategies deserve further consideration
      in large-scale cherry juice processing. Precentrifugation of juice before
      clarification and fining is immediately recommended.

PMID- 11513642
TI  - Effect of processing and storage on the antioxidant ellagic acid derivatives and
      flavonoids of red raspberry (Rubus idaeus) jams.
AB  - From red raspberries, ellagic acid, its 4-arabinoside, its 4' (4' '-acetyl)
      arabinoside, and its 4' (4' '-acetyl)xyloside, as well as quercetin and
      kaempferol 3-glucosides, were identified. In addition, two unidentified ellagic
      acid derivatives were detected. The free radical scavenging activity of the
      ellagic acid derivatives was evaluated by using the DPPH method and compared to
      that of Trolox. All of the isolated compounds showed antioxidant activity. The
      effect of processing to obtain jams on raspberry phenolics was evaluated. The
      flavonol content decreased slightly with processing and more markedly during
      storage of the jams. The ellagic acid derivatives, with the exception of ellagic
      acid itself, remained quite stable with processing and during 6 months of jam
      storage. The content of free ellagic acid increased 3-fold during the storage
      period. The initial content (10 mg/kg of fresh weight of raspberries) increased 2
      fold with processing, and it continued increasing up to 35 mg/kg after 1 month of
      storage of the jam. Then a slight decrease was observed until 6 months of storage
      had elapsed. The increase observed in ellagic acid could be explained by a
      release of ellagic acid from ellagitannins with the thermal treatment.

PMID- 11513643
TI  - Isoflavone transformation during soybean koji preparation and subsequent miso
      fermentation supplemented with ethanol and NaCl.
AB  - Soybeans were soaked with water for 4 h, steam-cooked, inoculated with the
      conidia of Aspergillus oryzae, and incubated for 3 days for koji preparation. The
      koji was then mixed with water-soaked and steam-cooked soybeans (1:2, w/w),
      ground into paste, and supplemented with 15% ethanol and 12.5% NaCl or 3% ethanol
      and 6% NaCl for miso fermentation at 30 degrees C. Daidzin, genistin, daidzein,
      and genistein contents were extracted from the lyophilized and pulverized soybean
      powder or from the miso homogenate by a developed one-tube procedure and analyzed
      with an HPLC. After water soaking, daidzein and genistein contents increased
      markedly, whereas daidzin and genistin contents decreased. Further increases of
      daidzein and genistein contents and decreases of daidzin and genistin contents
      were observed after koji mold growth. During fermentation, fungal and lactic acid
      bacterial (LAB) growth in the miso products was inhibited, whereas soluble
      protein contents increased much more rapidly in the low-salt miso products
      supplemented with 3% ethanol and 6% NaCl than the other products. When the 4- and
      8-week-fermented miso products were cooked with tofu for sensory evaluation,
      flavor ratings of the low-salt products were higher than that of a popular
      commercial product. In both products, the most daidzins and genistins were
      hydrolyzed after 4 weeks of fermentation. The hydrolytic enzymes contributing to
      isoflavone transformation originated from soybeans after water soaking and from
      koji with mold growth. It was of merit that the low-salt fermented products were
      fairly acceptable in flavor rating and rich in daidzein and genistein contents
      after 4 weeks of fermentation.

PMID- 11513644
TI  - Decrease in antigenic and allergenic potentials of ovomucoid by heating in the
      presence of wheat flour: dependence on wheat variety and intermolecular disulfide
      bridges.
AB  - The antigenic and allergenic activities of ovomucoid (OM) remaining in soluble
      fractions of pasta-like model samples of wheat flour mixed with egg white were
      investigated by ELISA competitive inhibition and immunoblotting analyses using a
      rabbit anti-OM IgG and the serum IgE specific for OM in patients allergic to egg
      white. The mixture of egg white and wheat flour of soft, hard, and durum
      varieties was kneaded for 10-50 min and benched for 1 h at RT, and then small
      pieces of the dough were heated in boiling 1% NaCl solution for 15 min. Even
      before heating, only after the kneading for 30 min or more, but not after
      kneading for only 20 min, followed by the benching, the antigenic activity of OM
      which remained in the phosphate-buffered saline extract from the dough markedly
      decreased. Almost no antigenic activity of OM was detected in the extracts of
      heated samples. Furthermore, in the extracts of heated durum samples, only a
      trace of or almost no IgE-reactive OM was detected against the five patients'
      sera. These reductive effects of wheat on the OM antigenicity and allergenicity
      were more remarkable in the durum variety than in the others. No detectable
      proteins were extracted with 1% SDS from the heated samples, whereas OM was
      extracted with 1% SDS containing 10% 2-mercaptoethanol, suggesting heat-induced
      polymerization through intermolecular disulfide bonds among OM and wheat.

PMID- 11513645
TI  - Effect of heat processing and storage time on migration of bisphenol A (BPA) and
      bisphenol A-diglycidyl ether (BADGE) to aqueous food simulant from Mexican can
      coatings.
AB  - Effects of heat processing and storage time (up to 70 days) on migration of
      bisphenol A (BPA) and bisphenol A-diglycidyl ether (BADGE) from can coatings into
      an aqueous food simulant were determined. Distilled water was canned in two types
      of Mexican cans: for tuna and for jalapeno peppers. Results showed that there is
      an effect of heat treatment on migration of both compounds. Storage time did not
      show any effect in BPA migration from tuna cans. There was an effect of storage
      time on BPA migration from jalapeno pepper cans. Results for BADGE migration were
      affected by its susceptibility to hydrolyze in aqueous simulants. BADGE
      concentration decreased, or was not detected, during storage in both types of
      cans. Migration levels for BPA and BADGE were within 0.6-83.4 and <0.25-4.3
      microg/kg, respectively. Both were below European and Mercosur legislation
      limits. Other migrating compounds were detected, although no identification was
      performed.

PMID- 11513646
TI  - Influence of aging conditions on the quality of red Sangiovese wine.
AB  - A red Sangiovese wine was stored in barrels of different woods (oak and chestnut)
      and types (225-L "barriques" and 1000-L barrels) at 12 and 22 degrees C for 320
      days to evaluate the effects of different aging conditions on wine quality.
      Chestnut barrels led to wines richer in phenolics, and which were more tannic,
      colored, and fruity. Oak barrels gave wines with more monomeric phenolics, but
      less astringent, with higher vanilla smell, and more harmonious. The type of
      barrel could be used as a parameter to regulate the extraction of wood components
      and the polymerization of monomeric phenolics. Storage at 22 degrees C favored
      the formation of polymerized phenolics and the increase of color density and
      color hue. The temperature produced less pronounced effects on aroma and taste,
      even if wines stored at 12 degrees C showed more harmony.

PMID- 11513647
TI  - Evolution of ellagitannins in Spanish, French, and American oak woods during
      natural seasoning and toasting.
AB  - The evolution of tannins in Spanish oak heartwood of Quercus robur L., Quercus
      petraea Liebl.,Quercus pyrenaica Wild., and Quercus faginea Lam. was studied in
      relation to the processing of wood in barrel cooperage. Their evolution was
      compared with that of French oak of Q. robur (Limousin, France) and Q. petraea
      (Allier, France) and American oak of Quercus alba L. (Missouri), which are
      habitually used in cooperage. Two stages of process were researched: the
      seasoning of woods during 3 years in natural conditions and toasting. Total
      phenol and total ellagitannin contents and optical density at 420 nm of wood
      extracts were determined. The ellagitannins roburins A-E, grandinin, vescalagin,
      and castalagin were identified and quantified by HPLC, and the molecular weight
      distribution of ellagitannins was calculated by GPC. During the seasoning process
      the different ellagitannin concentrations decreased according to the duration of
      this process and in the same way as those in French and American woods. The
      toasting process also had an important influence on the ellagitannin composition
      of wood. Roburins A-E, grandinin, vescalagin, and castalagin decreased during
      this process in the Spanish wood species, in the same proportion as in the French
      and American ones. Also, the seasoning and toasting processes lead to qualitative
      variations in the structure of ellagitannins, especially in the molecular weight
      distribution, as was evidenced by GPC analysis of their acetylated derivatives.

PMID- 11513648
TI  - Browning evaluation of ready-to-eat apples as affected by modified atmosphere
      packaging.
AB  - The color and polyphenol oxidase (PPO) activity of fresh-cut Golden delicious
      apples were evaluated throughout cold storage under modified atmospheres. The
      shelf life of cut apples was extended to several weeks, especially when an
      initial atmosphere of 90.5% N(2) + 7% CO(2) + 2.5% O(2) and plastic pouches of 30
      cm(3)/cm(2) x bar x 24 h were used. Under these conditions, a maximum 62% PPO
      activity depletion was observed. In all cases, the faster the initial PPO
      activity decays, the less the color changes. A fractional conversion first-order
      model was proposed for predicting color changes in minimally processed apples.
      Browning was better described through lightness (L) (k(L) = 0.017 - 0.07 day(-1))
      and color difference (Delta E*) values (k(Delta E) = 0.015 - 0.073 day(-1)),
      which fitted the model with enough accuracy.

PMID- 11513649
TI  - Electron paramagnetic resonance investigations of free radicals in extra virgin
      olive oils.
AB  - Free radicals in olive oils were identified and quantified by EPR, by means of
      the spin-trapping technique making use of alpha-phenylbutylnitrone (PBN) as spin
      trap. The radical species were identified as PBN-trapped hydroxyl radicals (PBN
      *OH) in the water microdroplets inside the fat medium. The largest radical
      concentration was 12.5 microM identical with 100%. The following were the
      relative concentrations of the radicals under different conditions: (1) Two oils,
      produced by continuous centrifugation, aged for 1 year, showed a 25-30% increase
      in the radicals compared to nonaged oils; 1-year-old oil, produced by pressure,
      did not differ from the nonaged oil. (2) Radical production was markedly reduced
      by N(2) bubbling; it was increased by heating, whereas it showed a biphasic
      pattern by air bubbling over time. (3) Radical concentration as a function of the
      UV irradiation time increased up to a maximum, after which it decreased and
      finally remained constant. The phenolic and oxygen contents were related to the
      radical content. This study demonstrates that the EPR technique is suitably
      applied to the detection of free radicals in olive oil and that storage,
      handling, and stress conditions of the oils significantly influence the radical
      concentration.

PMID- 11513650
TI  - Upgrading of maatjes herring byproducts: production of crude fish oil.
AB  - Fish oil has been extracted from byproducts of the maatjes (salted) herring
      production using a pilot plant consisting of a mincer, heat exchanger, and three
      phase decanter. The crude herring oil obtained had an initial peroxide value
      (PV), anisidine value (AV) and free fatty acids (FFA) level of only 3 mequiv of
      peroxide/kg of lipid, 8.9, and 2.9%, respectively. 5,8,11,14,17-Eicosapentaenoic
      acid (EPA) and 4,7,10,13,16,19-docosahexaenoic acid (DHA) were present in
      considerable amounts (99 and 91 g/kg, respectively). During storage of the oil,
      no photooxidation could be detected. Storage at room temperature led to
      significant autoxidation over time, apparent from primary and tertiary oxidation
      products, measured by a decrease of hydroperoxides and an increase of fluorescent
      compounds (FC). Storage at 50 degrees C resulted in significant increases in
      secondary (AV) and tertiary oxidation (FC) products. At all storage conditions,
      the FFA contents remained low (<3%) and the alpha-tocopherol content remained
      constant. These results open the possibility for fish oil production of good
      quality using salted herring byproducts.

PMID- 11513651
TI  - Production process contamination of citrus essential oils by plastic materials.
AB  - Twelve samples of plastic materials employed in the industrial extraction of
      citrus essential oils were analyzed for the presence of phosphorated
      plasticizers, chloroparaffins, and phthalate esters. The samples tested were
      found to release these contaminants into the essential oils during the production
      process. Contamination tests were carried out using dichloromethane and
      uncontaminated samples of citrus essential oils as extractants. The extracts were
      analyzed by HRGC/FPD, ECD, and MS. Only one sample of plastic material was found
      to release triaryl phosphates, 5 samples released chloroparaffins, 6 released
      diisobutyl phthalate, and 8 released bis(2-ethylhexyl) phthalate. Significantly
      larger quantities of contaminants were released by new plastic parts than by used
      plastic parts.

PMID- 11513652
TI  - Procedure to evaluate the stability during processing and storage of a medicated
      premix and medicated farm feed: erythromycin thiocyanate.
AB  - In this paper, a stability study of a medicated premix and medicated farm feed
      containing erythromycin thiocyanate was planned. No drug degradation was detected
      during the medicated farm feed processing. In the medicated premix stability
      study, significant drug degradation was detected only at 40 degrees C and 75%
      relative humidity. Because after 2 years of storage at 25 degrees C and 60%
      relative humidity no degradation of erythromycin thiocyanate was detected, this
      period of time is proposed as the premix shelf life. In the medicated farm feed
      stability study, drug degradation was detected under accelerated conditions, but
      it was not detected under long-term storage conditions for 3 months. Therefore,
      the proposed shelf life of the medicated farm feed is 3 months, as this is time
      enough to be consumed. The planned stability study-storage conditions, testing
      frequency, and proposed data evaluation-allowed an easy and reliable evaluation
      of veterinary medicine stability.

PMID- 11513653
TI  - Processing effects on lycopene content and antioxidant activity of tomatoes.
AB  - Consumption of tomato products has been associated with decreased risk of some
      cancer types, and the tomato antioxidant, lycopene, is thought to play an
      important role in the observed health effects. In this study, four carotenoids,
      trans-lycopene, phytofluene, phytoene, and zeta-carotene, were quantified in
      tomato products. Samples of raw tomatoes, tomato juice after hot break scalder,
      and final paste were obtained from two different processing plants over two
      years. Comparison of carotenoid levels throughout processing indicated that
      lycopene losses during processing of tomatoes into final paste (25-30 degrees
      Brix) ranged from 9 to 28%. The initial Brix level of the raw tomatoes appeared
      to influence the amount of lycopene loss that occurred, possibly due to the
      differences in processing time required to achieve the final desired Brix level
      of the paste. In general, no consistent changes in the other carotenoids were
      observed as a function of processing. The antioxidant activity of fresh tomatoes,
      tomato paste, and three fractions obtained from these products (i.e., aqueous,
      methanol, and hexane fractions) was also determined. In both a free radical
      quenching assay and a singlet oxygen quenching assay, significant antioxidant
      activity was found in both the hexane fraction (containing lycopene) and the
      methanol fraction, which contained the phenolic antioxidants caffeic and
      chlorogenic acid. The results suggest that in addition to lycopene, polyphenols
      in tomatoes may also be important in conferring protective antioxidative effects.

PMID- 11513654
TI  - Improvement of malt modification by use of Rhizopus VII as starter culture.
AB  - The development of a selected starter culture on malting barley and its effects
      on malt quality aspects were studied. Application of Rhizopus sporangiospores in
      a malting process resulted in increased beta-glucanase and xylanase contents of
      the malting barley and improved starchy endosperm cell-wall degradation.
      Activation of the sporangiospores and optimization of the inoculation procedure
      led to a further increase in enzyme levels and to larger and more consistent
      impacts on cell-wall modification. Whereas the main effect of the starter culture
      on beta-glucan degradation was observed during malting, a further decrease in
      beta-glucan during mashing suggests that the microbial enzymes that survived the
      kilning step were active during mashing. Other quality aspects that were
      influenced by the starter culture activity were protein modification, wort color,
      and wort pH. The level of microbial enzymes produced was related to the amount of
      barley kernels infected with the starter culture.

PMID- 11513655
TI  - Vanillin content in boiled peanuts.
AB  - A high-performance liquid chromatographic (HPLC) method for determination of
      vanillin in boiled peanuts has been developed. Vanillin was extracted with
      acetonitrile by blending at high speed followed by purification of an aliquot of
      the extract on a minicolumn packed with Al(2)O(3). Vanillin was quantitated by
      HPLC on silica gel with n-hexane/2-propanol/water/acetic acid (2100/540/37/2,
      v/v) as a mobile phase. The recovery of vanillin added to fresh peanut hulls at
      0.50 and 2.50 microg/g was 78.7 +/- 2.7 and 79.9 +/- 3.1%, respectively. The
      detection limit of vanillin in boiled peanuts was estimated at 0.05 microg/g. UV
      detector response to vanillin was linear to at least 2.5 microg/injection. Free
      vanillin has been found in two commercial brands of boiled peanuts at low ppm
      levels. Both the kernels and the hulls contained vanillin, which was formed
      during hydrolysis of lignin, one of the major constituents of the peanut hulls.
      Since vanillin has a low flavor threshold, it could be considered as one of the
      major ingredients that determines the flavor of boiled peanuts.

PMID- 11513656
TI  - Identification of impurities in technical anilofos and their effect on
      transplanted rice.
AB  - Seven impurities, namely, isopropylaniline (III), isopropylacetanilide (V),
      isopropylchloroacetanilide (VII), oxoanalogue (VIII), dithiodimer (IX),
      monothiodimer (X), and mercaptoacetanilide (XI), have been identified from
      technical anilofos. The quantification of each impurity was carried out by
      comparison with authentic samples of known concentration by GC and HPLC. The
      structure of authentic samples (synthesized and isolated) was established on the
      basis of NMR, IR, and MS spectral data. Bioassay of all the detected impurities
      along with three possible contaminants was carried out on transplanted rice under
      laboratory conditions. The oxo compound (VIII) was found to have an inhibitory
      effect on transplanted rice at 1 microg/g of soil.

PMID- 11513657
TI  - Plant odor analysis of apple: antennal response of codling moth females to apple
      volatiles during phenological development.
AB  - Volatile compounds were collected from apple branches (Malus domestica) at
      different developmental stages, and the antennal response of codling moth females
      (Cydia pomonella) to these compounds was recorded by electroantennography coupled
      to gas chromatography. Presence of a range of terpenoid compounds, many of which
      had antennal activity, was characteristic for volatile collections from branches
      with leaves, and from small green apples. Nine compounds from branches with
      leaves and green fruit consistently elicited an antennal response: methyl
      salicylate, (E)-beta-farnesene, beta-caryophyllene, 4,8-dimethyl-1,3(E),7
      nonatriene, (Z)3-hexenol, (Z,E)-alpha-farnesene, linalool, germacrene D, and
      (E,E)-alpha-farnesene. The bouquet emitted from flowering branches contained in
      addition several benzenoid compounds which were not found after bloom. Small
      green apples, which are the main target of codling moth oviposition during the
      first seasonal flight period, released very few esters. In comparison, fully
      grown apples released a large number of esters, but fewer terpenoids. The study
      of apple volatiles eliciting an antennal response, together with a survey of the
      seasonal change in the release of these compounds, is the first step toward the
      identification of volatiles mediating host-finding and oviposition in codling
      moth females.

PMID- 11513658
TI  - Allelochemicals in wheat (Triticum aestivum L.): cultivar difference in the
      exudation of phenolic acids.
AB  - Analysis by GC-MS/MS showed that a worldwide collection of 58 wheat accessions
      differed significantly in the amounts of 7 known phenolic acids exuded by the
      living roots of 17-day-old wheat seedlings. The quantities of exuded
      allelochemicals varied with the specific compound and ranged from 2.3 to 18.6,
      from 0.6 to 17.5, from 0.1 to 4.9, from 0.0 to 52.7, from 0.33 to 12.7, from 1.5
      to 20.5, and from 1.6 to 23.4 microg/L of water/agar for p-hydroxybenzoic,
      vanillic, cis-p-coumaric, syringic, cis-ferulic, trans-p-coumaric, and trans
      ferulic acids, respectively. The concentrations of p-hydroxybenzoic and vanillic
      acids exuded by wheat seedlings were normally distributed in the 58 accessions.
      The level of each phenolic acid in root exudates did not correlate well to that
      previously observed in wheat. In comparison with weakly allelopathic accessions,
      strongly allelopathic accessions exuded larger quantities of allelochemicals into
      the growth medium. The chemical basis for wheat seedling allelopathy is an area
      for further investigation.

PMID- 11513659
TI  - Hypervalent iodine compounds as potent antibacterial agents against ice
      nucleation active (INA) Pseudomonas syringae.
AB  - Twenty-three hypervalent iodine compounds belonging to aryliodonium salts, 1,
      aryliodonium ylides, 2, and (diacyloxyiodo)arenes, 3, were tested for their
      antibacterial activities against ice nucleation active (INA) Pseudomonas
      syringae, and the MIC and EC(50) values were determined. All of the compounds
      examined caused a dose-dependent decrease in bacterial growth rates. Aryliodonium
      salts, especially those with electron-withdrawing groups, exhibit higher
      antibacterial activities with MIC = 8-16 ppm, whereas the nature of the anion
      does not seem to affect the activities of the diaryliodonium salts.

PMID- 11513660
TI  - Analysis of pesticide gas cartridges.
AB  - Charcoal and sodium nitrate, the active ingredients in pesticide gas cartridges,
      are quantified via carbon analysis and ion chromatography, respectively.
      Linearity was excellent (R(2) > 0.995) over a range consisting of 50-150% of the
      target concentration for both ingredients. The coefficient of variation for the
      replicate analyses of gas cartridges over multiple days was <4% for both
      analytes. Using the results from the analysis of two batches of gas cartridges,
      theoretical populations were modeled and used to determine practical sampling
      strategies to support a quality control program for a gas cartridge manufacturing
      operation. This modeling indicates that the analysis of three cartridges from
      each of five different lots would produce mean values for both active ingredients
      that are within 5% of the true mean >99% of the time.

PMID- 11513661
TI  - Extraction and solubility characteristics of zein proteins from dry-milled corn.
AB  - Zein isolation by aqueous ethanol extraction from dry-milled corn produces a
      mixture of zeins, covalently linked polymers (dimers, tetramers, etc.) and higher
      molecular-weight aggregates, some of which were not soluble in aqueous alcohol.
      The insoluble particles were identified as protein aggregates which form when the
      extraction solution is heated, particularly under alkaline conditions. The
      insoluble protein aggregates were not present in zein isolated by the same method
      from corn gluten meal. Zeins extracted from corn gluten meal and dry-milled corn
      were fractionated (by differential solubility) to identify differences in their
      polypeptide compositions. Using polyacrylamide gel electrophoresis, beta- and
      gamma-zeins were detected in dry-milled corn, but only trace amounts of beta-zein
      were found in corn gluten meal. Treatment of dry-milled corn with 0.55% lactic
      acid and 0.2% sulfur dioxide at 50 degrees C for 6 h before ethanol extraction
      resulted in a 50% increase in zein isolate yield with high solubility (98%). This
      pre-extraction treatment cleaved disulfide linkages of the beta- and gamma-zeins
      and significantly reduced insoluble aggregates in zein isolates.

PMID- 11513662
TI  - Determination of polyphenolic profiles of Basque cider apple varieties using
      accelerated solvent extraction.
AB  - Polyphenols in the peel and pulp of 15 Basque cider apple varieties were
      determined by accelerated solvent extraction followed by reversed phase high
      performance liquid chromatography with diode array detection. It was observed
      that the polyphenolic composition in apple peel depended on varieties, whereas
      the main classes of phenolic compounds in apple pulp were flavan-3-ols and
      hydroxycinnamic acids in all cases, representing both together between 86 and 95%
      of total polyphenols assayed.

PMID- 11513663
TI  - Phytotoxic and fungitoxic activities of the essential oil of kenaf (Hibiscus
      cannabinus L.) leaves and its composition.
AB  - The chemical composition of the essential oil of kenaf (Hibiscus cannabinus) was
      examined by GC-MS. Fifty-eight components were characterized from H. cannabinus
      with (E)-phytol (28.16%), (Z)-phytol (8.02%), n-nonanal (5.70%), benzene
      acetaldehyde (4.39%), (E)-2-hexenal (3.10%), and 5-methylfurfural (3.00%) as the
      major constituents. The oil was phytotoxic to lettuce and bentgrass and had
      antifungal activity against Colletotrichum fragariae, Colletotrichum
      gloeosporioides, and Colletotrichum accutatum but exhibited little or no
      algicidal activity.

PMID- 11513664
TI  - Isolation and structure analysis of a glucomannan from the seeds of Libyan dates.
AB  - Polysaccharides extracted from seeds of Libyan dates with hot ethanol 80% (FI)
      and 0.1 M phosphate solution (FII) were fractionated and purified by ion-exchange
      and gel-filtration chromatography. According to methylation and hydrolysis
      analysis, the main chains of FI and FII consisted of (1-->4)-linked glucomannan;
      only traces of branched sugar residues were detected. This is the first report on
      the isolation of glucomannan from date seeds.

PMID- 11513665
TI  - Identification of species in animal feedstuffs by polymerase chain reaction-
      restriction fragment length polymorphism analysis of mitochondrial DNA.
AB  - Restriction site analysis of Polymerase Chain Reaction (PCR) products of
      cytochrome b mitochondrial DNA was applied to identify species in meat meal and
      animal feedstuffs. PCR was used to amplify a variable region of cytochrome b
      mitochondrial DNA gene. Species differentiation was determined by digestion of
      the obtained 359 bp amplicon with restriction enzymes, which generated species
      specific electrophoresis patterns; the sequencing of PCR products was used as
      confirming analysis. PCR-RFLP analysis revealed the presence of meat meal in
      animal feedstuffs and distinguished species of interest. The results supported
      the application of the method in control measures which should be adopted for
      meat-meal-based animal feed, as suggested by EU law. As a technical improvement,
      to simplify the analysis, the number of enzymes presented in this study for the
      detection of different species was smaller than others described in the
      literature; discrimination between ruminant and nonruminant species and between
      mammalian and poultry species was possible with few digestions.

PMID- 11513666
TI  - Comparison of dietary fiber contents of selected baby foods from two major brands
      in Canada using three methods.
AB  - Of the two major brands of baby foods in Canada, one reports lower dietary fiber
      values than the other, although the products appear to be similar. To investigate
      the reasons for this discrepancy, seven selected samples of baby foods from both
      brands were analyzed for total dietary fiber (TDF) according to the Mongeau
      (rapid Health Protection Branch; HPB) method. Two cereals were also analyzed by
      using the Prosky and the Englyst (nonstarch polysaccharide; NSP) methods as an
      internal check on the methodology as well as a means of investigating the reasons
      for the discrepancies. The sampling included at least four different lots of each
      product (cereals, fruits, vegetables, and legumes). Each lot was analyzed
      individually. The TDF values determined using the rapid HPB method were in
      agreement with those obtained by other dietary fiber methods. Comparison between
      manufacturer-reported and measured values showed that the low values reported in
      brand A products were due, in part, to under-reporting of TDF content: measured
      TDF values were significantly higher than manufacturer-reported values. For brand
      B products, the manufacturer-reported and measured TDF values were in general
      agreement. This shows that a large part of the discrepancy between the two brands
      was due to methodological problems associated with measuring TDF in brand A.
      Differences in TDF content were also apparent as shown by the fact that brand A
      TDF values were consistently lower than those of brand B when both were measured
      by the same method. The differences in TDF content were not explained by
      differences in the polysaccharide composition of the fiber residues or by
      differences in water content. Although the limited number of samples does not
      allow any general conclusion about the TDF content of specific brands, the
      results show that formulation and/or manufacturing differences may influence TDF
      values in processed baby foods.

PMID- 11513667
TI  - Novel fatty acid esters of p-coumaryl alcohol in epicuticular wax of apple fruit.
AB  - Hexane extracts of epicuticular wax from cv. Gala apples were noted to have an
      unusual, broad absorbance maximum at approximately 258 nm, which led us to
      isolate and identify the primary UV-absorbing compounds. Column and thin-layer
      chromatography yielded a fraction that gave a series of paired, 260-nm-absorbing
      peaks on C(18) HPLC. These were shown to be a family of phenolic fatty acid
      esters, for which retention times increased with increasing fatty acid chain
      length, and paired peaks were esters of two related phenolics with the same fatty
      acid moiety. Alkaline hydrolysis of the esters released two water-soluble
      phenolics separable by C(18) HPLC. Electrospray ionization mass spectrometry gave
      a molecular mass of 150 for both, and (1)H NMR plus UV absorbance spectra
      identified them as E and Z isomers of p-coumaryl alcohol. Alkaline cleavage of
      the fatty acid esters in the presence of methanol or ethanol resulted in partial
      derivatization of E-p-coumaryl alcohol to the corresponding gamma-O-methyl or O
      ethyl ether. Gradient HMQC NMR of the HPLC-purified stearate ester of E-p
      coumaryl alcohol indicated that fatty acid esterification occurs at the gamma-OH
      rather than at the 4-OH on the phenyl ring. This is the first report of fatty
      acid esters of monolignols as a natural plant product.

PMID- 11513668
TI  - Comparison of oil and phytosterol levels in germplasm accessions of corn,
      teosinte, and Job's tears.
AB  - Seeds of 49 accessions of corn (Zea mays ssp. mays), 9 accessions of teosinte
      (Zea species that are thought to be ancestors and probable progenitors to corn),
      and 3 accessions of Job's tears (Coix lacryma), obtained from a germplasm
      repository, were ground and extracted with hexane. Whole kernel oil yields and
      levels of four phytonutrients (free phytosterols, fatty acyl phytosterol esters,
      ferulate phytosterol esters, and gamma-tocopherol) in the oils were measured.
      Among the seeds tested, oil yields ranged from 2.19 to 4.83 wt %, the levels of
      ferulate phytosterol esters in the oil ranged from 0.047 to 0.839 wt %, the
      levels of free phytosterols in the oil ranged from 0.54 to 1.28 wt %, the levels
      of phytosterol fatty acyl esters in the oil ranged from 0.76 to 3.09 wt %, the
      levels of total phytosterols in the oil ranged from 1.40 to 4.38 wt %, and the
      levels of gamma-tocopherol in the oil ranged from 0.023 to 0.127 wt %. In
      general, higher levels of all three phytosterol classes were observed in seed
      oils from accessions of Zea mays ssp. mays than in seed oils from accessions of
      the other taxonomic groups. The highest levels of gamma-tocopherol were observed
      in teosinte accessions.

PMID- 11513669
TI  - Isolation and HPLC quantitative analysis of flavonoid glycosides from Brazilian
      beverages (Maytenus ilicifolia and M. aquifolium).
AB  - Aqueous infusions of Brazilian Maytenus leaves are used as beverages, foodstuffs,
      and phytomedicines. Previously, we isolated two new flavonoid tetrasaccharides
      from the infusion of Maytenus aquifolium leaves that showed antiulcer activity.
      In this investigation a new flavonoid tetrasaccharide, kaempferol-3-O-alpha-L
      rhamnopyranosyl (1-->6)-O-[alpha-L-arabinopyranosyl (1-->3)-O-alpha-L
      rhamnopyranosyl (1-->2)]-O-beta-D-galactopyranoside (3), was isolated, together
      with kaempferol tri- and disaccharides and quercetin trisaccharides from the
      aqueous infusion of Maytenus ilicifolia leaves. All structures were elucidated by
      ES-MS and NMR spectroscopic methods. The quantitative analysis of the flavonoid
      glycosides from Maytenus ilicifolia and M. aquifolium has been performed by HPLC.

PMID- 11513670
TI  - Protein and lysine content, grain yield, and other technological traits in durum
      wheat under Mediterranean conditions.
AB  - A major problem for durum wheat production in the Mediterranean region is yield
      fluctuation. This fluctuation is a result of year-to-year variation in
      precipitation and heat stress during grain growth, which is typical of the
      Mediterranean climate. Both yield stability and good quality are needed in
      adapted durum wheat ideotypes. Ten durum wheat cultivars differing in drought
      resistance were grown during 1998, under both rainfed and irrigated conditions,
      at three sites in southern Spain. The main traits studied were protein and lysine
      content, grain yield, test weight, SDS sedimentation, semolina color, and grain
      vitreousness. Results show a high influence of site on all traits. Only test
      weight (TW), SDS sedimentation, grain vitreousness, and protein per kernel
      appeared to be determined also by cultivar effect. Vitreousness was positively
      correlated with TW (r = 0.48**) and semolina color (r = 0.46**). An inverse
      relationship was found between grain yield and protein content. Regression of
      cultivar mean values of protein content and grain yield showed a negative
      correlation (r = -0.72***), probably due to dilution of protein by non-nitrogen
      compounds and reduced starch accumulation in the grain under drought conditions.
      Lysine content was negatively associated with protein content (r = -0.86***),
      indicating the difficulty of a simultaneous breeding for both characteristics.

PMID- 11513671
TI  - Comparison of major and trace element concentrations in Danish greenhouse
      tomatoes (Lycopersicon esculentum Cv. Aromata F1) cultivated in different
      substrates.
AB  - The concentration of major and trace elements was determined for tomato
      (Lycopersicon esculentumcv. Aromata F1) fruits grown in three different substrate
      systems. The systems were soil and rockwool irrigated with a normal nutrient
      solution and rockwool irrigated with a nutrient solution with elevated electrical
      conductivity (EC). At three harvest times, tomato fruits were analyzed for Ca,
      Cu, Fe, K, Mg, Mn, Na, P, S, Sr, and Zn by ICP-AES and for Cd, Cr, Mo, Ni, Pb,
      Sn, and V by HR-ICPMS. The concentrations of Ca, Cd, Fe, Mn, Mo, Na, Ni, Sr, and
      Zn were significantly different (p < 0.05) for tomato fruits grown on the
      different substrates. Between the harvest times different levels (p < 0.05) were
      shown for Ca, Cd, Fe, Mn Na, Ni, Sr, Zn Cu, K, Mg, P, Sn, and V. The
      concentration of Cd was >15 times higher and the concentration of Ca was 50-115%
      higher in soil-grown fruits than in rockwool-grown fruits. Principal component
      analysis applied on each harvest split the data into two groups. One group
      includes soil-grown fruits, and the other group includes rockwool-grown fruits
      with the two different nutrient solutions.

PMID- 11513672
TI  - Kinetics and mechanism of imazosulfuron hydrolysis.
AB  - Knowledge of the kinetics and pathways of hydrolytic degradation is crucial to
      the prediction of the fate and transport mechanism of chemicals. This work first
      describes the kinetics of the chemical hydrolysis of imazosulfuron, a new
      sulfonylurea herbicide, and evaluates the results to propose a degradation
      pathway. The hydrolysis of imazosulfuron has been studied in aqueous buffers both
      within the pH range 1.9-12.3 at ambient temperature (thermostated at 25 +/- 2
      degrees C) and at pH 3.6 within the temperature range of 15-55 degrees C. The
      hydrolysis rate of imazosulfuron was characterized by a first-order kinetics, pH-
      and temperature-dependent, and accelerated by acidic conditions and higher
      temperatures. The calculated half-lives at pH 4.5 and 5.9 were 36.5 and 578 days,
      respectively. At pH 6.6, 7.4, 9.2, and 12.3 no significant change in
      imazosulfuron concentration was observed after 150 days. Half-lives were much
      lower at pH <4 (= imazosulfuron pK(a)), at which they ranged from 3.3 to 6.3
      days. Moreover, a change in temperature from 15 to 25 degrees C in acidic
      conditions (pH 3.6) decreased the half-life of imazosulfuron by a factor of
      approximately 4.0; in any case, a 3-5-fold increase in the rate of hydrolysis was
      found for each 10 degrees C increase in temperature. In acidic conditions the
      only hydrolysis products were the two molecules resulting from the cleavage of
      the sulfonylurea bridge.

PMID- 11513673
TI  - Identification of the major metabolites of prochloraz in rainbow trout by liquid
      chromatography and tandem mass spectrometry.
AB  - The metabolic pattern of the imidazole fungicide prochloraz [N-propyl-N-[2-(2,4,6
      trichlorophenoxy)ethyl]imidazole-1-carboximide] was investigated in rainbow trout
      (Oncorhynchus mykiss). Following a single oral administration of
      [(14)C]prochloraz, levels 4.3 +/- 4.1 and 3.9 +/- 1.8% of the dose were excreted
      in the bile after 48 h in male and female animals, respectively. Urinary
      radioactivity accounted for 1.3 +/- 0.4 and 2.4 +/- 1.1% of the dose over the
      same period in males and females. Metabolites from both matrices were separated
      by reversed-phase HPLC with radioactive detection and analyzed by positive and/or
      negative electrospray ionization mass spectrometry. No unchanged prochloraz was
      detected in the analyzed excreta. The major biotransformation products in bile
      were the aldehyde corresponding to the cleavage of the imidazole ring, N-2-(2,4,6
      trichlorophenoxy)ethylurea, and the glucuronide conjugate of 2,4,6
      trichlorophenoxyethanol. In urine, the major metabolite was 2,4,6
      trichlorophenoxyacetic acid. On the basis of enzymatic hydrolysis by beta
      glucuronidase and LC-MS analyses, this study demonstrates that rainbow trout are
      able to biotransform prochloraz, mainly as glucuronide conjugates.

PMID- 11513674
TI  - Linear free energy study of ring-substituted aniline ozonation for developing
      treatment of aniline-based pesticide wastes.
AB  - The relative rate constants for the reaction of ozone were determined for several
      substituted anilines in aqueous solutions at pH 6.5 and 1.5. At pH 6.5, with the
      exception of m- and p-nitroaniline, the rate constants obey Hammett's equation:
      log(k(X)/k(H)) = rho sigma. The departure of m- and p-nitroaniline may be
      explained by direct conjugation of the reaction center. The commonly used
      sigma(p)(-) value of 1.27, which extends the range of applicability of the
      Hammett equation, was insufficient to account for the conjugation effects on
      ozonation of p-nitroaniline; rho = -1.48 (R = 0.973). Use of amine group atomic
      charge determinations significantly improved correlations: (k(X)/k(H)) = 48.7
      delta - 18.2 (R = 0.996). A linear plot of Hammett constants versus relative rate
      data at pH 1.5 showed poor correlation: rho = 0.72 (R = 0.572). Poor correlation
      was similarly observed for amine group atomic charge determinations, suggesting
      varied reaction mechanisms.

PMID- 11513675
TI  - Mobility and leachability of zinc in two soils treated with six organic zinc
      complexes.
AB  - A study of soil columns was conducted to evaluate Zn movement potential in two
      reconstructed soil profiles. Zn-phenolate, Zn-EDDHA, Zn-EDTA, Zn-lignosulfonate,
      Zn-polyflavonoid, and Zn-heptagluconate were applied in the upper zone of the
      column. The different physicochemical properties of the two soils and the
      micronutrient source may influence Zn leaching, the distribution of Zn among soil
      fractions, and the Zn available to the plant in the depth of the layers. In Aquic
      Haploxeralf soil, the application of six fertilizers produced little migration
      and very small leaching of Zn in the soil profiles. In Calcic Haploxeralf soil,
      Zn-EDTA migrated and was distributed throughout the soil columns. This Zn chelate
      produces a loss of Zn by leaching, which was 36% of the added Zn. In the latter
      soil, Zn leached very little with the other five fertilizer treatments. The same
      as for these organic Zn complexes, the retention of added Zn indicated the
      potential of metal accumulation in the A(p) horizons of the two soil profiles. A
      large portion of applied Zn was available to plants
      [diethylenetriaminepentaacetic acid (DTPA) and Mehlich-3 extractable Zn] in the
      depths reached by the different commercial formulations. The relationship between
      the two methods was highly significant (Mehlich-3-Zn = 1.25 + 1.13 DTPA-Zn, R(2)
      = 99.19%). When Zn was added as Zn-EDTA, the amounts of the most labile fractions
      (water-soluble plus exchangeable and organically complexed Zn) increased
      throughout the entire profile column in comparison with the control columns,
      although in the B(t) horizon of the Aquic Haploxeralf soil they increased only
      slightly.

PMID- 11513676
TI  - Predicting pesticide emissions and downwind concentrations using correlations
      with estimated vapor pressures.
AB  - Pesticide emissions to air have been shown to correlate with compound vapor
      pressure values taken from the published literature. In the present study,
      emissions correlations based on vapor pressures derived from chemical property
      estimation methods are formulated and compared with correlations based on the
      literature data. Comparison was made by using the two types of correlations to
      estimate emission rates for five herbicides, a fungicide, and an insecticide, for
      which field-measured emission rates from treated soil, foliage, and water were
      available. In addition, downwind concentrations were estimated for two
      herbicides, three fungicides, four insecticides, and two fumigants, for which
      concentration measurements had been made near treated sources. The comparison
      results demonstrated that correlations based on vapor pressures derived from
      chemical property estimation methods were essentially equivalent to correlations
      based on literature data. The estimation approach for vapor pressures is a viable
      alternative to the inherently more subjective process of selecting literature
      values.

PMID- 11513677
TI  - Seasonal and spatial studies on pesticide residues in surface waters of the
      Shinano river in Japan.
AB  - Water samples collected once a week from early April 1996 to the end of August
      1996 from four sites on the Shinano River in Japan were analyzed for pesticides
      and their metabolites using a gas chromatograph-mass spectrometer. Among the
      total of 53 chemicals found, 22 were herbicides, 15 were insecticides, 11 were
      fungicides, and 5 were metabolites. The concentrations of chemicals found ranged
      from 3 ng/L (bromobutide) to 8200 ng/L (isoprothiolane). Herbicides were found
      primarily during May and June at all four sites. Insecticides and fungicides were
      found primarily during July and August at all four sites. The presence of
      pesticides in the river water correlated with the time of pesticide application
      to the rice fields near the river.

PMID- 11513678
TI  - Purification and characterization of molybdenum species from Medicago sativa
      (alfalfa) grown on mine tailings.
AB  - Extraction, purification, and identification procedures were developed for the
      chemical investigation of molybdenum (Mo) in freeze-dried aerial portions of
      alfalfa (Medicago sativa L.) collected from a reclaimed tailings pond at the
      Highland Valley Copper mine in British Columbia. The purification procedures were
      guided by ICP and colorimetric analyses. The methods included development of an
      efficient aqueous extraction protocol, sample cleanup by partitioning against n
      butanol, and filtration through diatomaceous earth. Further purification was
      achieved by anion-exchange chromatography, elution with aqueous NaCl, and
      desalting by gel filtration. Final purification of the Mo-containing fraction was
      carried out using preparative anion-exchange HPLC. Molybdenum was found to be
      present in its purified form as the molybdate anion (MoO(4)(2-)) primarily on the
      basis of multinuclear ((1)H, (13)C, and (95)Mo) NMR studies.

PMID- 11513679
TI  - Environmental distribution of acetochlor, atrazine, chlorpyrifos, and
      propisochlor under field conditions.
AB  - The environmental behavior, movement, distribution, persistence, and runoff by
      rainfall of the pesticides acetochlor, atrazine, chlorpyrifos, and propisochlor
      were studied under field conditions during a five-month period at normal weather
      conditions. The pesticide concentrations in soil depths of 0-5 and 5-20 cm, and
      in sediment and runoff water samples (collected from an artificial reservoir
      built in the lower part of the experimental plot) were measured every second week
      and following every runoff event. The contamination of a stream running across
      the lowest part of the plot was also monitored. The weather conditions were also
      recorded at the experimental site. The pesticide residues were quantified by a
      capillary gas chromatograph equipped with a nitrogen phosphorus selective
      detector (GC-NPD). There was a consistent decrease in pesticide residues in the 0
      5 cm soil layer with time after spaying. At 140 days after treatment only
      atrazine and chlorpyrifos were present; acetochlor and propisochlor were not
      detected in this soil layer. Atrazine and chlorpyrifos in the soil at a depth of
      5-20 cm were detectable during the whole experimental interval, whereas
      acetochlor and propisochlor concentrations were below the limit of detection.
      Pesticide losses by the surface runoff process and the contamination of the
      stream were closely related to the time of rainfall elapsed after treatment and
      amount of rain at the experimental plots. Losses were primarily dependent on
      surface rainfall volume and intensity. The maximum detected residues of atrazine
      and acetochlor in stream water were 1 order of magnitude higher than the maximum
      residue limit specified by the European Union (EU) for environmental and drinking
      water (0.1 microg/L for individual compounds and 0.5 microg/L for total
      pesticides). Chlorpyrifos and propisochlor were not detected in this matrix.

PMID- 11513680
TI  - Practical synthesis of 3-methylnonane-2,4-dione, an intense strawlike and fruity
      flavored compound.
AB  - A practical synthesis of 3-methylnonane-2,4-dione, which is an intense strawlike
      and fruity flavored compound, has been performed by the aldol condensation of n
      hexanal and methyl ethyl ketone, followed by oxidation using sodium hypochlorite
      in the presence of 4-benzoyloxy-2,2,6,6-tetramethylpiperidine-N-oxide in an
      overall yield of 59%. The purification of 3-methylnonane-2,4-dione with high
      purity was performed via copper complexes.

PMID- 11513681
TI  - Use of GC-olfactometry to identify the hop aromatic compounds in beer.
AB  - This paper describes a sensorial aroma extract dilution analysis (AEDA) approach
      to the analysis of beer aromas derived from hops. To obtain an extract with an
      odor representative of the original product, the XAD extraction procedure was
      applied and the experimental conditions were optimized. The aromagrams of three
      beers were compared: one brewed without hops, one brewed with Saaz hop pellets,
      and one brewed with Challenger hop pellets. One spicy/hoppy compound, unmodified
      from hop to beer, proved responsible for the most intense odor in both hopped
      beer extracts. Another flavoring compound in hops, linalool, also survives
      through the process to the final beer. Other compounds such as gamma-nonalactone
      and humuladienone, although not found in our extracts of hop, significantly
      modify beer aromagrams after hopping. Sulfur compounds characteristic of
      Challenger hops proved to be at least partially responsible for the unpleasant
      flavor found in the corresponding beer.

PMID- 11513682
TI  - Aroma compounds in the production of liquid beet sugar.
AB  - Samples of in-process liquid beet sugar were collected from three different parts
      of a beet sugar factory and a refinery. The samples were analyzed with respect to
      aroma compounds by means of both liquid-liquid extraction and gas-phase
      (headspace) extraction followed by gas chromatography-olfactometry (GC-O) and GC
      mass spectrometry (GC-MS). The aromas of the eluted compounds were evaluated
      qualitatively and quantitatively for the different samples. In general, earthy
      and sour aromas were often present in the raw juice sample, whereas caramel
      aromas were mainly present in the samples taken further downstream in the
      process. For fruity, floral, and solvent-like aromas, different parallel trends
      were noted. Some aromas were present only at the beginning of the process,
      whereas others developed toward the end of the process.

PMID- 11513683
TI  - Aroma properties of a homologous series of 2,3-epoxyalkanals and trans-4,5
      epoxyalk-2-enals.
AB  - A few odor-active epoxyaldehydes, formed during lipid peroxidation, have recently
      been reported as intense aroma compounds in foods. However, very little is known
      about their flavor properties in general. Syntheses of homologous trans-2,3
      epoxyalkanals (C(6)-C(12)) and trans-4,5-epoxy-(E)-2-alkenals (C(7)-C(12))
      followed by structural characterization using mass spectrometry (MS/EI; MS/CI)
      and (1)H NMR measurements were performed. An evaluation of their odor qualities
      and odor thresholds by gas chromatography-olfactometry revealed the following:
      within the trans-2,3-epoxyalkanals, the odor quality changed from grassy for the
      compounds with six and seven carbon atoms to citrus-like or soapy for aldehydes
      with eight and more carbon atoms. The odor thresholds lay in the range of 3-15
      ng/L (in air) and were nearly identical within the series; however, a slight
      minimum was measured for trans-2,3-epoxyoctanal to trans-2,3-epoxydecanal. In the
      series of the trans-4,5-epoxyalk-(E)-2-enals the C(10) compound was characterized
      by the lowest odor threshold of 0.6-2.5 pg/L of air. However, all trans-4,5-epoxy
      alk-(E)-2-enals smelled intensely metallic.

PMID- 11513684
TI  - Formation of Strecker aldehydes and pyrazines in a fried potato model system.
AB  - Sugars and amino acids were removed from potato slices by soaking in water and
      ethanol. They were then infused with various combinations of sugars (glucose
      and/or fructose) and amino acids (asparagine, glutamine, leucine, isoleucine,
      phenylalanine, and/or methionine) and fried. Volatile compounds were trapped onto
      Tenax prior to gas chromatography-mass spectrometry. Relative amounts of
      compounds (relative to the internal standard) and relative yields (per mole of
      amino acid infused into the slices) were determined. Amounts of 10 pyrazines, 4
      Strecker aldehydes, and 4 other compounds were monitored. Relative amounts and
      relative yields of compounds varied according to the composition of the system.
      For the single amino acid-glucose systems, leucine gave the highest relative
      amount and relative yield of its Strecker aldehyde. Asparagine and phenylalanine
      gave the highest total relative amount and total relative yield, respectively, of
      pyrazines. In the system containing all of the amino acids and glucose, the
      relative amount of 3-methylbutanal was higher, whereas the amounts of the other
      monitored Strecker aldehydes were lower. Most of the relative amounts of
      individual pyrazines were lower compared to the glucose-asparagine system,
      whereas the total relative yield of pyrazines was lower, compared to all of the
      single amino acid-glucose mixtures. Addition of fructose to the mixed amino acid
      glucose model system generated Strecker aldehydes and pyrazines in ratios that
      were more similar to those of untreated potato chips than to those from the same
      system but without fructose. Both the sugars and the amino acids present in
      potato are crucial to the development of flavor compounds in fried potato slices.

PMID- 11513685
TI  - Aroma compound sorption by oak wood in a model wine.
AB  - Oak wood used for wine barrels was immersed into a model wine containing eight
      aroma compounds (e.g., aromatic and terpene alcohols, ethyl esters, and
      aldehyde), for which activity coefficients in water and model wine were
      determined using the mutual solubility measurement. A mass balance of these
      volatiles considering their reactivity in model wine was established. For most of
      the studied aroma compounds, and mainly for linalool and ethyl octanoate, a
      sorption behavior into wood was reported for the first time. This phenomenon was
      selective and could not be related to the solubilities in model wine and
      hydrophobicities of the studied aroma compounds, suggesting that acid-base and
      polar characteristics of wood were more involved in this sorption mechanism. This
      study has also shown that the level of sorption is a function of the ratio of
      wood surface area/solution volume.

PMID- 11513686
TI  - Effect of salivary components on volatile partitioning from solutions.
AB  - Partition of fourteen volatile compounds, representing the diverse
      physicochemical properties of aroma compounds, was measured by static equilibrium
      headspace in solutions containing the components of artificial saliva, either
      singly or in mixtures. Comparison of a bovine salivary mucin and pig gastric
      mucin showed no significant difference in partition behavior of the volatiles, so
      gastric mucin was used. Mucin viscosity changed with pH, but binding of volatile
      compounds did not show a marked dependence on pH. All combinations of the
      salivary components were tested for their effect on partition. Three types of
      behavior were noted. Partition of some compounds was unaffected by mucin, and
      with other compounds mucin decreased partition, whereas another group showed a
      decrease with mucin that was affected by the presence of salivary salts and
      sugar. When volatiles or sugar were added to a mucin solution, the final
      headspace concentration depended on the order of addition, indicating some
      competition for binding. These solute-mucin effects are discussed in relation to
      mucin structure and behavior in solution.

PMID- 11513687
TI  - Protein-enriched spaghetti fortified with corn gluten meal.
AB  - Spaghetti was prepared by replacing either 5 or 10% semolina or farina with corn
      gluten meal, a high-protein fraction from the wet milling of corn, to increase
      the protein content of pasta. Spaghetti fortified with corn gluten meal had a
      similar cooked weight and cooking loss but was less firm compared with the
      control. The overall flavor quality score of the spaghetti decreased with the
      increasing additions of either water-washed, water/ethanol-washed or regular corn
      gluten meal because of the higher intensity of the fermented flavor. Spaghetti
      with acceptable quality can be prepared with 5% water/ethanol-washed corn gluten
      meal, thereby improving its nutritional value while providing an additional
      market for corn gluten meal.

PMID- 11513688
TI  - Association of end-product adducts with increased IgE binding of roasted peanuts.
AB  - Recently, we have shown that roasted peanuts have a higher level of IgE binding
      (i.e., potentially more allergenic) than raw peanuts. We hypothesized that this
      increase in IgE binding of roasted peanuts is due to an increased levels of
      protein-bound end products or adducts such as advanced glycation end products
      (AGE), N-(carboxymethyl)lysine (CML), malondialdehyde (MDA), and 4-hydroxynonenal
      (HNE). To support our hypothesis, we produced polyclonal antibodies (IgG) to each
      of these adducts, determined their levels in raw and roasted peanuts, and
      examined their ability to bind to IgE from a pooled serum of patients with
      clinically important peanut allergy. Results showed that AGE, CML, MDA, and HNE
      adducts were all present in raw and roasted peanuts. Roasted peanuts exhibited a
      higher level of AGE and MDA adducts than raw peanuts. IgE was partially inhibited
      in a competitive ELISA by antibodies to AGE but not by antibodies to CML, MDA, or
      HNE. This indicates that IgE has an affinity for peanut AGE adducts. Roasted
      peanuts exhibited a higher level of IgE binding, which was correlated with a
      higher level of AGE adducts. We concluded that there is an association between
      AGE adducts and increased IgE binding (i.e., allergenicity) of roasted peanuts.

PMID- 11513689
TI  - Removal of ochratoxin A in red wines by means of adsorption treatments with
      commercial fining agents.
AB  - The presence in wine of the fungal metabolite, ochratoxin A (OTA), represents a
      serious risk for consumer health. A variety of fining agents, including activated
      carbon, silica gel, potassium caseinate, egg albumin, and gelatin, was evaluated
      in relation to their abilities to remove OTA in fortified wines. Freundlich
      adsorption isotherms were used to model the adsorption behavior between
      ochratoxin A and the fining agent. Potassium caseinate and activated carbon were
      found to be the best fining agents that could be used to remove OTA in wine.
      Potassium caseinate removed up to 82% of OTA when used at 150 g/hL, whereas
      activated carbon showed the highest specific adsorption capacity due to a high
      surface area per mass and low adsorption of total polyphenols.

PMID- 11513690
TI  - Partial purification of polyphenol oxidase from Chinese cabbage Brassica rapa L.
AB  - Polyphenol oxidase (PPO) was purified and characterized from Chinese cabbage by
      ammonium sulfate precipitation and DEAE-Toyopearl 650M column chromatography.
      Substrate staining of the crude protein extract showed the presence of three
      isozymic forms of this enzyme. The molecular weight of the purified enzyme was
      estimated to be approximately 65 kDa by gel filtration on Toyopearl HW-55F. On
      SDS-PAGE analysis, this enzyme was composed of a subunit molecular weight of 65
      kDa. The optimum pH was 5.0, and this enzyme was stable at pH 6.0 but was
      unstable below pH 4.0 or above pH 7.0. The optimum temperature was 40 degrees C.
      Heat inactivation studies showed temperatures >40 degrees C resulted in loss of
      enzyme activity. PPO showed activity to catechol, pyrogallol, and dopamine (K(m)
      and V(max) values were 682.5 mM and 67.6 OD/min for catechol, 15.4 mM and 14.1
      OD/min for pyrogallol, and 62.0 mM and 14.9 OD/min for dopamine, respectively).
      The most effective inhibitor was 2-mercaptoethanol, followed in decreasing order
      by ascorbic acid, glutathione, and L-cysteine. The enzyme activity of the
      preparation was maintained for 2 days at 4 degrees C but showed a sudden
      decreased after 3 days.

PMID- 11513691
TI  - Effect of pH on the rheological and structural properties of gels of water-washed
      chicken-breast muscle at physiological ionic strength.
AB  - Adjustment of pH from 6.4 to neutrality improved gelling ability and water
      holding capacity of twice water-washed, minced chicken-breast muscle
      significantly at physiological ionic strength, at which the majority of the
      myofibrillar proteins, including myosin, are not soluble. A strain value of 2.2
      was obtained at neutral pH. Myofibrils were the main components of the gel
      network at both pH 6.4 and 7.0; however, the myofibrillar distribution varied
      with the pH value. At pH 6.4, myofibrils formed a network of localized aggregates
      leaving large voids between, whereas at neutral pH, an evenly distributed network
      of myofibrils was formed. In addition, at neutral pH, a network of fine strands
      was found within the network of myofibrils. The network was much less developed
      at pH 6.4. The thin and thick filaments within each myofibrillar structure were
      disorganized at both pH values. The intramyofibrillar spaces were larger at
      neutral pH than at pH 6.4. It was proposed that adjustment of pH to neutrality
      increased electrostatic repulsion leading to a more even distribution of the
      myofibrillar proteins, a key factor responsible for the improved gel strength and
      water-holding capacity.

PMID- 11513692
TI  - Effects of phenolic propyl esters on the oxidative stability of refined sunflower
      oil.
AB  - The oxidative stability of refined sunflower oil in the presence and in the
      absence of propyl caffeate (PC), propyl hydrocaffeate (PHC), propyl ferulate
      (PF), and propyl isoferulate (PI) has been evaluated according to the Rancimat
      method. The antioxidant activity of the phenolic derivatives was compared with
      that obtained with native [alpha-tocopherol (alpha-TOH)] and synthetic [propyl
      gallate (PG)] antioxidants. The results allow the establishment of a decreasing
      order of antioxidant power: PG > PHC > PC >> alpha-TOH > PI > PF. The oxidative
      stability was improved neither by the addition of PF nor by a supplement of alpha
      TOH. Moreover, a positive antioxidant effect was obtained for PC that was placed
      between those of alpha-TOH and PG. The antioxidant activity of PHC was higher
      than that of its analogue (PC). A dose-dependent effect was observed for PG, PHC,
      and PC. A chain-breaking mechanism was proposed for the antioxidant activity of
      propyl phenolic esters because the same ranking order of efficacy was obtained
      for their antiradical activities evaluated by using the 2,2-diphenyl-1
      picrylhydrazyl radical method.

PMID- 11513693
TI  - Evaluation of the dietetic and therapeutic potential of a high molecular weight
      hydroxycinnamate-derived polymer from Symphytum asperum Lepech. Regarding its
      antioxidant, antilipoperoxidant, antiinflammatory, and cytotoxic properties.
AB  - A water-soluble hydroxycinnamate-derived polymer (>1000 kDa) from Symphytum
      asperum Lepech. (Boraginaceae) strongly reduced the diphenylpicrylhydrazyl
      radical (IC(50) approximately 0.7 microg/mL) and inhibited the nonenzymatic lipid
      peroxidation of bovine brain extracts (IC(50) approximately 10 ng). This polymer
      exhibited only a low hydroxyl radical scavenging effect in the Fe(3+)-EDTA
      H(2)O(2) deoxyribose system (IC(50) > 100 microg/mL) but strongly decreased
      superoxide anion generation in either the reaction of phenazine methosulfate with
      NADH and molecular oxygen (IC(50) approximately 13.4 microg/mL) or in rat PMA
      activated leukocytes (IC(50) approximately 5 microg/mL). The ability to inhibit
      both degranulation of azurophil granules and superoxide generation in primed
      leukocytes indicates that the NADPH oxidase responsible for this later effect is
      inhibited, pointing to the Symphytum asperum polymer as a potent antiinflammatory
      and vasoprotective agent. At all concentrations tested (0-200 microg/mL), we
      observed no cytotoxicity on normal human fibroblasts and neither
      antiproliferative effects nor proliferation activation on neoplastic cells.

PMID- 11513694
TI  - Oxidation in fish oil enriched mayonnaise: ascorbic acid and low pH increase
      oxidative deterioration.
AB  - The effect of ascorbic acid (0-4000 ppm) and pH (3.8-6.2) on oxidation and levels
      of iron and copper in various fractions of mayonnaise enriched with 16% fish oil
      was investigated. Ascorbic acid induced release of iron from the assumed oil
      water interface into the aqueous phase at all pH levels, but this effect of
      ascorbic acid was strongest at low pH (pH 3.8-4.2). Ascorbic acid generally
      promoted formation of volatile oxidation compounds and reduced the peroxide value
      in mayonnaises. Peroxide values and total volatiles generally increased with
      decreasing pH values, suggesting that low pH promoted oxidation. It is proposed
      that iron bridges between the egg yolk proteins low-density lipoproteins,
      lipovitellin, and phosvitin at the oil-water interface are broken at low pH
      values, whereby iron ions become accessible as oxidation initiators. In the
      presence of ascorbic acid, oxidation is further enhanced due to the reduction of
      Fe(3+) to Fe(2+) that rapidly catalyzes lipid oxidation via lipid hydroperoxide
      decomposition at the oil-water interface in mayonnaise.

PMID- 11513695
TI  - Correlation of the protein structure and gelling properties in dried egg white
      products.
AB  - The relationship between protein structure and aggregation, as well as heat
      induced gelling properties, of seven dried egg white (DEW) products was
      investigated. Strong correlations were found between average molecular weight and
      hydrophobicity plus surface SH groups of DEW-soluble protein aggregate (SPA).
      This suggests that hydrophobic interactions and disulfide bond formation between
      protein molecules were involved in the aggregation. The average molecular weight
      of DEW products with alkaline pHs was relatively higher than those with neutral
      pHs and the same degree of protein unfolding, probably because of more disulfide
      bond formation between protein molecules. In addition, strong correlations were
      found between hydrophobicity, surface SH groups plus average molecular weight of
      DEW-SPA, and physical properties of the gels from DEW products. These data
      indicated that controlling the aggregation of DEW proteins in the dry state is
      crucial to controlling the gelling properties of DEW.

PMID- 11513696
TI  - Capsanthone 3,6-epoxide, a new carotenoid from the fruits of the red paprika
      Capsicum annuum L.
AB  - The structure of a new carotenoid, isolated from the fruits of the red tomato
      shaped paprika Capsicum annuum L., was elucidated to be (3S,5R,6S,5'R)-3,6-epoxy
      5,6-dihydro-5-hydroxy-beta,kappa-carotene-3',6'-dione by spectroscopic analyses,
      including fast atom bombardment collision-induced dissociation-mass
      spectrometry/mass spectrometry (FAB CID-MS/MS) and was designated capsanthone 3,6
      epoxide. Capsanthone 3,6-epoxide is assumed to be an oxidative metabolite of
      capsanthin 3,6-epoxide in paprika.

PMID- 11513697
TI  - Characterization of phenolic compounds in virgin olive oil and their effect on
      the formation of carcinogenic/mutagenic heterocyclic amines in a model system.
AB  - Mutagenic heterocyclic amines (HAs) are formed at low levels during cooking of
      meat and fish, and some of them are considered to be possible human carcinogens.
      The formation of HAs may be affected by the presence of synthetic or naturally
      occurring antioxidants. In the present study the effect of virgin olive oil (VOO)
      phenolic compounds, identified and quantified by LC-MS, on the formation of HAs
      in a model system was evaluated. An aqueous solution of creatinine, glucose, and
      glycine was heated in the presence of two samples of VOO differing only in the
      composition of phenolic compounds. The addition of VOO to the model system
      inhibited the formation of 2-amino-3-methylimidazo[4,5-f]quinoxaline (IQx), 2
      amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), and 2-amino-3,7,8
      trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) by between 30 and 50% compared with
      the control. Fresh-made olive oil, which contained a high amount of
      dihydroxyphenylethanol derivatives, inhibited HA formation more than a 1-year-old
      oil did. The inhibition of HA formation was also verified using phenolic
      compounds extracted from VOO.

PMID- 11513698
TI  - New oleanane saponins in Chenopodium quinoa.
AB  - Six triterpenoid saponins were isolated from the seeds of Chenopodium quinoa
      (Chenopodiaceae). Their structures were as follows: phytolaccagenic acid 3-O
      [alpha-L-arabinopyranosyl-(1' '-->3')-beta-D-glucuronopyranosyl]-28-O-beta-D
      glucopyranoside (1); spergulagenic acid 3-O-[beta-D-glucopyranosyl-(1-->2)-beta-D
      glucopyranosyl-(1-->3)-alpha-L-arabinopyranosyl-28-O-beta-D-glucopyranoside (2);
      hederagenin 3-O-[beta-D-glucopyranosyl-(1-->3)-alpha-L-arabinopyranosyl]-28-O
      beta-D-glucopyranoside (3); phytolaccagenic acid 3-O-[beta-D-glucopyranosyl-(1-
      >4)-beta-D-glucopyranosyl-(1-->4)-beta-D-glucopyranosyl]-28-O-beta-D
      glucopyranoside (4); hederagenin 3-O-[beta-D-glucopyranosyl-(1-->4)-beta-D
      glucopyranosyl-(1-->4)-beta-D-glucopyranosyl]-28-O-beta-D-glucopyranoside (5);
      and spergulagenic acid 3-O-[alpha-L-arabinopyranosyl-(1' '-->3')-beta-D
      glucuronopyranosyl]-28-O-beta-D-glucopyranoside (6). Saponins 5 and 6 are new.
      The structures were characterized on the basis of hydrolysis and spectral
      evidence, including IR, UV, optical rotations, 1D- and 2D-NMR (HMQC and HMBC),
      ESIMS, and FABMS analyses.

PMID- 11513699
TI  - Quantitative study of fruit flavonoids in citrus hybrids of King (C. nobilis) and
      Mukaku Kishu (C. kinokuni).
AB  - Twenty-four Citrus hybrids of King (C. nobilis) and Mukaku Kishu (C. kinokuni)
      were examined for their flavonoid profiles of the edible part by reversed-phase
      HPLC analysis. Two hybrids (G-155 and G-156) contained higher amounts of
      natsudaidain than their parents, whereas the remainder of the hybrids had a
      character intermediate between those of King and Mukaku Kishu on the basis of
      polymethoxylated flavone composition. Principal component analysis revealed the
      distribution of the hybrids by quantifying 23 flavonoid contents.

PMID- 11513700
TI  - Identification of anthocyanins in berries by narrow-bore high-performance liquid
      chromatography with electrospray ionization detection.
AB  - Qualitative determination of anthocyanins in extracts of red fruits by narrow
      bore HPLC/ESI-MS was carried out. This method was used to investigate anthocyanin
      contents of black bilberry (Vaccinium myrtillus L.), blackberry (Rubus sp.), and
      mulberry (Morus nigra). An ultraviolet diode array and a mass spectrometer with
      ESI source were used for detection. Anthocyanin identifications were made by
      using retention time data and UV-vis and mass spectra and comparing them with
      those of commercially available standard compounds. The method allowed the
      identification of fourteen anthocyanins in black bilberry extract, six
      anthocyanins in blackberry extract, and five anthocyanins in mulberry extract.

PMID- 11513701
TI  - Analysis of free fatty acids in whey products by solid-phase microextraction.
AB  - To evaluate the impact of Cheddar cheese starter cultures on the level of free
      fatty acids in liquid whey, a solid-phase microextraction (SPME) technique was
      utilized. The determination of response factors relative to an internal standard
      and the verification of linearity over a wide concentration range allowed for the
      quantitation of free fatty acids in experimentally produced liquid whey and in a
      wide range of dry whey ingredients. Results indicated that whey produced with a
      Lactococcus lactis subsp. lactis starter culture contained the highest level of
      total free fatty acids with significantly higher levels of lauric, myristic, and
      palmitic acids. Significant declines in oleic, linoleic, and palmitic acid
      occurred during storage. Commercial whey ingredients demonstrated a linear
      increase in free fatty acids with increasing percent protein, except for whey
      protein isolate, which had the lowest concentration. The use of SPME for the
      rapid analysis of free fatty acids in whey products should allow for further
      research to determine the importance of these compounds on the quality and
      stability of whey products.

PMID- 11513702
TI  - The wide diversity of structurally similar wine proteins.
AB  - In the present work, single grape variety wines, Moscatel and Arinto, were used.
      Analysis by denaturing polyacrylamide gel electrophoresis of the wine proteins
      revealed the presence of only a few polypeptides ranging in molecular mass from
      15 to 30 kDa. However, a more detailed examination of the whole protein fraction,
      by a combination of techniques, showed that these wines contain a very large
      number (many tens and, possibly, many more) of distinct polypeptides, exhibiting
      similar molecular masses but different electrical charges. The results obtained
      using highly specific antibodies and N-terminal sequencing indicate that there is
      structural similarity among most of the wine polypeptides. These observations can
      be explained by the existence of a common precursor to most or all of the wine
      proteins, which could generate all of the detected polypeptides by limited
      proteolysis. Comparison of the N-terminal sequences of the polypeptides isolated
      from Moscatel wine with proteins from other sources revealed a high degree of
      homology to pathogenesis-related proteins.

PMID- 11513703
TI  - Reversible conformational change in beta-lactoglobulin A modified with N
      ethylmaleimide and resistance to molecular aggregation on heating.
AB  - beta-Lactoglobulin A (beta LG A) modified with N-ethylmaleimide (NEM-beta LG A)
      was purified by ion exchange chromatography, and modification of beta LG A by NEM
      was confirmed by time of flight mass spectrometry and 5,5'-dithiobis(2
      nitrobenzoic acid) methods. The fluorescent spectrum of NEM-beta LG A was
      slightly different from that of native beta LG A. NEM-beta LG A gave no
      polymerization after heating at 80 degrees C and pH 7.5, as shown by
      polyacrylamide gel electrophoresis. Conformational change of NEM-beta LG A was
      observed at 80 degrees C by ultraviolet differential spectra, whereas after
      cooling it recovered to its original state as before heating, indicating apparent
      reversible thermal denaturation. Native beta LG A is resistant to pepsin
      hydrolysis, whereas heated beta LG A was easily hydrolyzed by pepsin. NEM-beta LG
      A before heating was also resistant to pepsin hydrolysis, and after heating NEM
      beta LG A was still resistant to pepsin hydrolysis. These results indicate that
      NEM-beta LG A maintained a conformation similar to its native form even after
      heating. Addition of 0.2 M NaCl to the beta LG A heated under salt-free condition
      induced polymerization of heated beta LG A molecules, but not that of heated NEM
      beta LG A. This seemed to indicate that the formation of inter- or intramolecular
      disulfide linkage made the heat-induced conformational change of beta LG A
      irreversible.

PMID- 11513704
TI  - Suppression of chemical mutagen-induced SOS response by alkylphenols from clove
      (Syzygium aromaticum) in the Salmonella typhimurium TA1535/pSK1002 umu test.
AB  - A methanol extract from clove (Syzygium aromaticum) showed a suppressive effect
      of the SOS-inducing activity on the mutagen 2-(2-furyl)-3-(5-nitro-2
      furyl)acrylamide (furylfuramide) in the Salmonella typhimurium TA1535/pSK1002 umu
      test. The methanol extract was re-extracted with hexane, dichloromethane, ethyl
      acetate, butanol, and water. The hexane fraction showed a suppressive effect.
      Suppressive compounds in the hexane fraction were isolated by silica gel column
      chromatography and identified as trans-isoeugenol (1) and eugenol (2) by GC, GC
      MS, IR, and (1)H and (13)C NMR spectroscopy. Compounds 1 and 2 suppressed the
      furylfuramide-induced SOS response in the umu test. Compounds 1 and 2 suppressed
      42.3 and 29.9% of the SOS-inducing activity at a concentration of 0.60
      micromol/mL. These compounds were assayed with other mutagens, 4-nitroquinolin 1
      oxide (4NQO) and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). In addition,
      compounds 1 and 2 were assayed with aflatoxin B(1) (AfB(1)) and 3-amino-1,4
      dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1), which require liver metabolizing
      enzymes. These compounds showed suppressive effects of the SOS-inducing activity
      against furylfuramide, 4NQO, AfB(1), and Trp-P-1. To research the structure
      activity relationship, methyl esters of 1 and 2 (1Me and 2Me) and o-eugenol (3),
      as compounds similar to 2, were also assayed with all mutagens. Compounds 1Me,
      2Me, and 3 showed weak suppressive effects of the SOS-inducing activity against
      furylfuramide.

PMID- 11513705
TI  - Stability of capsinoid in various solvents.
AB  - To investigate the stability of capsinoid in solvents, the quantitative change of
      vanillyl nonanoate, a synthetic model capsinoid, in various solvents was measured
      by HPLC. Vanillyl nonanoate was stable in nonpolar solvents, whereas it was
      labile in polar solvents. In particular, vanillyl nonanoate tended to decompose
      in protic solvents such as alcohol and water. Structures of the decomposition
      products from vanillyl nonanoate in methanol and ethanol were determined to be
      methyl and ethyl vanillyl ethers, respectively. To clarify the decomposition
      mechanism of capsinoid, six analogues of vanillyl nonanoate were tested. The
      stability of the analogues in organic solvents suggested that the hydroxyl group
      in the para-position of the benzene ring largely contributes to the decomposition
      of capsinoid.

PMID- 11513706
TI  - Effects of glycerol and moisture gradient on thermomechanical properties of white
      bread.
AB  - The thermomechanical properties of breadcrumb were investigated using dynamic
      mechanical analysis (DMA) and differential scanning calorimetry (DSC). The main
      transition (T(1), near 0 degrees C) shifted to lower temperature with added
      glycerol due to freezing point depression. The low-temperature transition (T(3),
      approximately -50 degrees C), found only in high-glycerol (8.8%) bread, suggested
      that of excess or phase-separated glycerol. The high-temperature transition
      (T(2), 60-85 degrees C) appeared only in aged breadcrumbs; its temperature range
      was correlated well with the amylopectin melting transition (DSC) but its tan
      delta amplitude did not correlate well with the amylopectin melting enthalpy
      (r(2) = 0.72). On the other hand, the change of E' ' (viscous behavior) suggested
      that T(2) might be related to the change in the amorphous region. Domain-to
      domain (amorphous) and crumb-to-crust moisture migrations are two critical
      phenomenological changes associated with aging and could lead to significant
      local dehydration of some amorphous regions contributing to mechanical firming
      during storage.

PMID- 11513707
TI  - Hydration properties and the role of water in taste modalities of sucrose,
      caffeine, and sucrose-caffeine mixtures.
AB  - Solution properties of sapid molecules are informative on their type of hydration
      (hydrophobic or hydrophilic) and on the extent of the hydration layer.
      Physicochemical properties (intrinsic viscosity and apparent specific volume) and
      nuclear magnetic resonance (NMR) relaxation rates R(1) and R(2) for pure sucrose,
      bitter molecule caffeine, and their mixture were found to be relevant in the
      interpretation of the effects of these solutes on water mobility. Likewise,
      surface tension, contact angles with a hydrophobic surface, and the adhesion
      forces to this type of surface of the aqueous solutions of sapid molecules were
      found to discriminate between their effects on water cohesion and also between
      their taste qualities. The interpretation of the two sets of independent
      experimental results, namely physicochemical and spectroscopic data, helps in the
      elucidation of the role of water in sweet and bitter taste chemoreception.

PMID- 11513708
TI  - Interface characterization and aging of bovine serum albumin stabilized oil-in
      water emulsions as revealed by front-surface fluorescence.
AB  - This paper is devoted to the application of front-surface fluorescence to the
      study of aging and oxidation of oil-in-water emulsions. Emulsions with two oil
      droplet sizes were stabilized with bovine serum albumin (BSA) and stored at 37 or
      47 degrees C. Lipid oxidation was demonstrated by measurement of hydroperoxides
      and headspace pentane. Front-surface fluorescence spectra (excitation wavelength
      = 355 nm) revealed gradual formation of oxidized lipid-protein adducts during the
      4 weeks of storage. Fluorescence (excitation = 290 nm) of BSA tryptophanyl
      residues (Trp) declined during the first day of aging and then decreased slightly
      and linearly. Fourth-derivative Trp spectra exhibited peaks at 316 and 332 nm.
      Their evolution indicated that the ratio of Trp in hydrophobic environments to
      total Trp increased in small droplet emulsions. This suggests that, during lipid
      oxidation, the adsorbed and nonadsorbed protein underwent various degrees of Trp
      degradations, polymerization, and aggregation. Thus, front-surface fluorescence
      makes it possible to evaluate, noninvasively, protein modification and lipid
      oxidation end-products during processing and storage of food emulsions.

PMID- 11513709
TI  - Pressure-induced denaturation of monomer beta-lactoglobulin is partially
      irreversible: comparison of monomer form (highly acidic pH) with dimer form
      (neutral pH).
AB  - This study was conducted to assess the effect of high hydrostatic pressure on
      monomer beta-lactoglobulin (BLg) at acid pH by fluorescence spectroscopy under
      pressure and by circular dichroism (CD) and (1)H NMR spectroscopies after release
      of pressure. The intrinsic (tryptophan) fluorescence measurement and the study of
      8-anilinonaphthalene-1-sulfonate (ANS) binding to BLg indicated that at pH 2.0
      the recovery of center of spectral mass or ANS fluorescence was almost complete
      upon pressure release. No difference in (1)H NMR spectra was observed between
      pressurized and unpressurized BLg. In addition, NMR detection of the H/D exchange
      of aromatic protein indicated that the conformation of the vicinity of tryptophan
      residues could be refolded almost completely after release of pressure. These
      results seemingly confirm that the pressure-induced denaturation of BLg at pH 2.0
      is reversible. However, cis-parinaric acid binding ability of pressurized BLg was
      largely lost, although its retinol binding ability was the same as its
      unpressurized one. Furthermore, CD spectra of the far-UV region and 2D NMR
      spectra evidently revealed the difference in the conformation of the molecule
      between unpressurized and pressurized BLg. These results are interpreted as an
      existence of partially fragile structure in the BLg molecule by high pressure.

PMID- 11513710
TI  - Competitive inhibition of mushroom tyrosinase by 4-substituted benzaldehydes.
AB  - A kinetic study of the inhibition of mushroom tyrosinase by 4-substituted
      benzaldehydes showed that these compounds behave as classical competitive
      inhibitors, inhibiting the oxidation of L-3,4-dihydroxyphenylalanine (L-DOPA) by
      mushroom tyrosinase (o-diphenolase activity). The kinetic parameter (K(I))
      characterizing this inhibition was evaluated for all of the seven compounds
      assayed. Cuminaldehyde showed the most potent inhibitory activity (K(I) = 9
      microM). It also inhibited the oxidation of L-tyrosine by mushroom tyrosinase (o
      monophenolase activity) in a competitive manner. The corresponding kinetic
      parameter for this inhibition was evaluated (K(I) = 0.12 mM).

PMID- 11513711
TI  - Characterization of betacyanin oxidation catalyzed by a peroxidase from Beta
      vulgaris L. roots.
AB  - A protein fraction with peroxidase (EC 1.11.1.7) activity against guaiacol from
      Beta vulgaris L. roots oxidized both betanidin and betanin (betanidin 5-O-beta-D
      glucoside), the former being the more efficient substrate for the enzyme. The
      protein fraction contained three strongly basic perxidase isoenzymes. Betanidin
      quinone was formed as the only product in the course of enzymatic betanidin
      oxidation, whereas betalamic acid and several oxidized cyclo-DOPA 5-O-beta-D
      glucoside polymers were generated during the oxidation of betanin. In accordance
      with the catalytic properties of peroxidase, a possible mechanism for betanidin
      oxidation is proposed. This mechanism includes the formation of a betanidin
      radical, which, by further dismutation, yields betanidin quinone and betanidin.
      The betanidin oxidation rate showed a Michaelis-type dependence on the substrate
      concentration. The apparent K(M) for the reaction was 0.46 mM. On the basis of
      the spectral properties of the enzyme responsible for both betanidin and betanin
      oxidations, its peroxidase nature is suggested.

PMID- 11513712
TI  - In vivo studies on the metabolism of the monoterpenes S-(+)- and R-(-)-carvone in
      humans using the metabolism of ingestion-correlated amounts (MICA) approach.
AB  - The major in vivo metabolites of S-(+)- and R-(-)-carvone in a metabolism of
      ingestion correlated amounts (MICA) experiment were newly identified as alpha,4
      dimethyl-5-oxo-3-cyclohexene-1-acetic acid (dihydrocarvonic acid), alpha
      methylene-4-methyl-5-oxo-3-cyclohexene-1-acetic acid (carvonic acid), and 5-(1,2
      dihydroxy-1-methylethyl)-2-methyl-2-cyclohexen-1-one (uroterpenolone) on the
      basis of mass spectral analysis in combination with syntheses and NMR
      experiments. Minor metabolites were identified as reduction products of carvone,
      namely, the alcohols carveol and dihydrocarveol. The previously identified major
      in vivo metabolite in rabbits, 10-hydroxycarvone, could not be detected,
      indicating either concentration effects or interspecies differences. Metabolic
      pathways for carvone in humans including oxidation of the double bond in the side
      chain and, to a minor extent 1,2- and 1,4 + 1,2-reduction of carvone, are
      discussed. No differences in metabolism between S-(+)- and R-(-)-carvone were
      detected.

PMID- 11513713
TI  - Berry phenolics and their antioxidant activity.
AB  - Phenolic profiles of a total of 26 berry samples, together with 2 apple samples,
      were analyzed without hydrolysis of glycosides with HPLC. The phenolic contents
      among different berry genera varied considerably. Anthocyanins were the main
      phenolic constituents in bilberry, bog-whortleberry, and cranberry, but in
      cowberries, belonging also to the family Ericaceae genus Vaccinium, flavanols and
      procyanidins predominated. In the family Rosaceae genus Rubus (cloudberry and red
      raspberry), the main phenolics found were ellagitannins, and in genus Fragaria
      (strawberry), ellagitannins were the second largest group after anthocyanins.
      However, phenolic acids were dominant in rowanberries (genus Sorbus) and
      anthocyanins in chokeberry (genus Aronia). In the family Grossulariaceae genus
      Ribes (currants and gooseberry), anthocyanins predominated, as well as in
      crowberries (family Empetraceae genus Empetrum). In apples, hydroxycinnamic acids
      were the main phenolic subgroup. Extraction methods for berries and apples were
      studied to produce phenolic extracts with high antioxidant activity. Evaluation
      of antioxidant activity was performed by autoxidazing methyl linoleate (40
      degrees C, in the dark). The extraction method affected remarkably both the
      phenolic composition and the antioxidant activity, but with statistical analysis
      the observed activity could not be well explained with the contents of individual
      phenolic subgroups.

PMID- 11513714
TI  - Determination of antioxidant and antimicrobial activities of Rumex crispus L.
      extracts.
AB  - The antioxidant activities, reducing powers, 2,2-diphenyl-1-picrylhydrazyl (DPPH)
      scavenging activities, amount of total phenolic compounds, and antimicrobial
      activities of ether, ethanol, and hot water extracts of the leaves and seeds of
      Rumex crispus L. were studied. The antioxidant activities of extracts increase
      with increasing amount of extracts (50-150 microg). However, the water extracts
      of both the leaves and seeds have shown the highest antioxidant activities. Thus,
      addition of 75 microg of each of the above extracts to the linoleic acid emulsion
      caused the inhibition of peroxide formation by 96 and 94%, respectively. Although
      the antioxidant activity of the ethanol extract of seed was lower than the water
      extract, the difference between these was not statistically significant, P >
      0.05. Unlike the other extracts, 75 microg of the ether extract of seeds was
      unable to show statistically significant antioxidant activity, P > 0.05 (between
      this extract and control in that there is no extract in the test sample). Among
      all of the extracts, the highest amount of total phenolic compound was found in
      the ethanol extract of seeds, whereas the lowest amount was found in the ether
      extract of seeds. Like phenolic compounds, the highest reducing power and the
      highest DPPH scavenging activity were found in the ethanol extract of seeds.
      However, the reducing activity of the ethanol extract of seeds was approximately
      40% that of ascorbic acid, whereas in the presence of 400 microg of water and
      ethanol extracts of seeds scavenging activities were about 85 and 90%,
      respectively. There were statistically significant correlations between amount of
      phenolic compounds and reducing power and between amount of phenolic compounds
      and percent DPPH scavenging activities (r = 0.99, P < 0.01, and r = 0.864, P <
      0.05, respectively) and also between reducing powers and percent DPPH scavenging
      activities (r = 0.892, P < 0.05). The ether extracts of both the leaves and seeds
      and ethanol extract of leaves had shown antimicrobial activities on
      Staphylococcus aureus and Bacillus subtilis. However, none of the water extracts
      showed antimicrobial activity on the studied microorganisms.

PMID- 11513715
TI  - Antioxidant effects of phenolic rye (Secale cereale L.) extracts, monomeric
      hydroxycinnamates, and ferulic acid dehydrodimers on human low-density
      lipoproteins.
AB  - Dietary antioxidants that protect low-density lipoprotein (LDL) from oxidation
      may help to prevent atherosclerosis and coronary heart disease. The antioxidant
      activities of purified monomeric and dimeric hydroxycinnamates and of phenolic
      extracts from rye (whole grain, bran, and flour) were investigated using an in
      vitro copper-catalyzed human LDL oxidation assay. The most abundant ferulic acid
      dehydrodimer (diFA) found in rye, 8-O-4-diFA, was a slightly better antioxidant
      than ferulic acid and p-coumaric acid. The antioxidant activity of the 8-5-diFA
      was comparable to that of ferulic acid, but neither 5-5-diFA nor 8-5-benzofuran
      diFA inhibited LDL oxidation when added at 10-40 microM. The antioxidant activity
      of the monomeric hydroxycinnamates decreased in the following order: caffeic acid
      > sinapic acid > ferulic acid > p-coumaric acid. The antioxidant activity of rye
      extracts was significantly correlated with their total content of monomeric and
      dimeric hydroxycinnamates, and the rye bran extract was the most potent. The data
      suggest that especially rye bran provides a source of dietary phenolic
      antioxidants that may have potential health effects.

PMID- 11513716
TI  - Antioxidative activity of volatile chemicals extracted from beer.
AB  - Volatile chemicals obtained from a commercial beer by liquid-liquid continuous
      extraction were evaluated for antioxidant activity. The inhibitory ability of
      this extract toward the conversion of hexanal to hexanoic acid was monitored over
      a 35-day period. The volatile extract demonstrated >99% effectiveness at
      inhibiting hexanal oxidation at 50 microg/mL, comparable to that of the natural
      antioxidant alpha-tocopherol (vitamin E). Volatile compounds contained in the
      extract were isolated and identified by gas chromatography-mass spectrometry (GC
      MS). From the volatile constituents identified in beer extract, phenylethyl
      alcohol, maltol, and 2-furanmethanol were examined for antioxidative activities.
      At a concentration of 500 microg/mL, maltol and 2-furanmethanol demonstrated
      approximately 95 and 100% inhibition of hexanal oxidation over 35 days,
      respectively. Phenylethyl alcohol did not show any appreciable level of
      inhibition of hexanal oxidation. Heterocyclic compounds, some of which are known
      to possess antioxidative activities, were also identified in the volatile
      extract.

PMID- 11513717
TI  - Metabolic fate of (-)-[4-(3)H]epigallocatechin gallate in rats after oral
      administration.
AB  - After oral administration of [4-(3)H]EGCg to rats, the radioactivity in blood,
      major tissues, urine, and feces was measured over time. The radioactivity in
      blood and most tissues remained low for 4 h postdose, began to increase after 8
      h, peaked at 24 h, and then decreased. Major urinary excretion of radioactivity
      occurred in the 8-24 h period, and the cumulative radioactivity excreted by 72 h
      was 32.1% of the dose. The radioactivity in the feces was 35.2% of the dose
      within 72 h postdose. In the case of rats pretreated with antibiotics (antibiotic
      pretreated rats), the radioactivity levels of the blood and urine were definitely
      lower than those in rats not pretreated with antibiotics (normal rats). The
      radioactivity recovered in the antibiotic-pretreated rat urine was estimated to
      be only (1)/(100) of that in the normal rat urine. These results clearly
      demonstrated that the radioactivity detected in the blood and urine of normal
      rats mostly originated from degradation products of EGCg produced by intestinal
      bacteria. Furthermore, a main metabolite in the normal rats was purified and
      identified as 5-(5'-hydroxyphenyl)-gamma-valerolactone 3'-O-beta-glucuronide (M
      2). In feces of the normal rats, EGC (40.8% of the fecal radioactivity) and 5
      (3',5'-dihydroxyphenyl)-gamma-valerolactone (M-1, 16.8%) were detected. These
      results suggested that M-1 was absorbed in the body after degradation of EGCg by
      intestinal bacteria, yielding M-1 with EGC as an intermediate. Furthermore, M-2
      was thought to be formed from M-1 in the intestinal mucosa and/or liver, then to
      enter the systemic circulation, and finally to be excreted in the urine. Taking
      into account all of the above findings, a possible metabolic route of EGCg orally
      administered to rats is proposed.

PMID- 11513718
TI  - Reaction of fumonisin with glucose prevents promotion of hepatocarcinogenesis in
      female F344/N rats while maintaining normal hepatic sphinganine/sphingosine
      ratios.
AB  - The reaction of the primary amine of fumonisin B(1) (FB(1)) with glucose was
      hypothesized to detoxify this mycotoxin. Eighty 10-day-old female F344/N rats
      were injected intraperitoneally with diethylnitrosamine (DEN; 15 mg/kg of body
      weight). At 4 weeks of age, the weaned rats were randomly assigned to one of four
      treatment groups with 20 rats each. At 9 weeks of age, four rats from each
      treatment group were killed. At 12 weeks, another five rats from each group were
      killed. At 20 weeks of age, the remaining rats were killed. In comparison with
      the rats fed basal diet or FB(1)-glucose (containing 25 ppm of FB(1)), rats fed 8
      ppm (residual amount of free FB(1) in the FB(1)-glucose mixture) or 25 ppm of
      FB(1) had greater alanine aminotransferase activity at 9 and 20 weeks of age (P <
      0.001), greater endogenous hepatic prostaglandin E(2) production at 20 weeks of
      age (P < 0.05), and significantly lower plasma cholesterol at 20 weeks of age (P
      < 0.01). Placental glutathione S-transferase (PGST)-positive and gamma
      glutamyltransferase (GGT)-positive altered hepatic foci (AHF) occurred only in
      rats fed 25 ppm of FB(1) at 20 weeks of age. Hepatic natural killer (NK) cell
      activities were similar among the four groups, but the percentage of total liver
      associated mononuclear cells exhibiting the NKR-P1(bright) marker was
      significantly greater in rats fed FB(1)-glucose, FB(1) (8 ppm) and FB(1) (25 ppm)
      than in control rats at 9 weeks of age, and FB(1)-glucose-treated rats had
      significantly lower NKR-P1(bright) cells as a percentage of total liver
      associated mononuclear cells than rats fed 25 ppm of FB(1) at 20 weeks of age (P
      < 0.05). PGST- or GGT-positive AHF were not detected in any treatment group at 9
      or 12 weeks of age. At 20 weeks of age, half of the rats fed 25 ppm of FB(1) had
      PGST- and GGT-positive AHF. The sphinganine (Sa) concentration and the
      Sa/sphingosine (So) ratio were significantly greater in the rats fed 25 ppm of
      FB(1) diet as compared with the control groups at, respectively, 12 or 20 weeks
      of age. Therefore, modifying FB(1) with glucose seems to prevent FB(1)-induced
      hepatotoxicity and promotion of hepatocarcinogenesis. The Sa/So ratio was not the
      most sensitive biomarker of FB(1) toxicity.

PMID- 11513719
TI  - Aflatoxins and fumonisins in corn from the high-incidence area for human
      hepatocellular carcinoma in Guangxi, China.
AB  - A comparative study on the natural occurrence of aflatoxins and Fusarium toxins
      was conducted with corn samples from high- and low-incidence areas for human
      primary hepatocellular carcinoma (PHC) in Guangxi, China. In samples from the
      high-risk area, aflatoxin B(1) was the predominant toxin detected in terms of
      quantity and frequency, with its concentration ranging between 9 and 2496
      microg/kg and an 85% incidence of contamination. Among the samples, 13 (76%)
      exceeded the Chinese regulation of 20 microg/kg for aflatoxin B(1) in corn and
      corn-based products intended for human consumption. Significant differences in
      aflatoxin B(1), B(2), and G(1) and total aflatoxin concentrations in corn between
      the areas were found (P < 0.05). The average daily intake of aflatoxin B(1) from
      corn in the high-risk area was 184.1 microg, and the probable daily intake is
      estimated to be 3.68 microg/kg of body weight/day, 3.20 times the TD(50) in rats.
      Corn samples from both areas were simultaneously contaminated with fumonisins
      B(1), B(2), and B(3). Aflatoxin B(1) may play an important role in the
      development of PHC in Guangxi.

PMID- 11513720
TI  - Identification, determination, and biological evaluation of a novel styrene
      trimer contained in polystyrene food containers. 2.
AB  - An unidentified styrene trimer (ST) isolated from the acetonitrile extract of
      polystyrene (PS) food containers was characterized as (1S*,6R*,7S*,8S*,11R*)-6,11
      diphenyltricyclo[6,2,2,0(2,7)]dodeca-2,9-diene. The content and migration of this
      compound in PS food containers were determined by GC-MS (SIM). Furthermore, an
      endocrine-disrupting effect was tested using in vitro and in vivo assays of the
      compound. In conclusion, it seems that the compound does not present the effect.

PMID- 11513721
TI  - Arsenic in cooked seafood products: study on the effect of cooking on total and
      inorganic arsenic contents.
AB  - Total and inorganic arsenic contents were analyzed in cooked seafood products
      consumed in Spain during the period July 1997-June 1998: hake, meagrim, small
      hake, anchovy, Atlantic horse mackerel, sardine, bivalves, crustaceans, squid,
      and salted cod. Various cooking treatments were used (grilling, roasting, baking,
      stewing, boiling, steaming, and microwaving). The results obtained were compared
      statistically with those found previously in the same products raw, and they
      showed that after cooking there was a significant increase in the concentration
      of total arsenic for salted cod and bivalves, and in the concentration of
      inorganic arsenic for bivalves and squid. The mean content of inorganic arsenic
      was significantly higher in bivalves than in any other type of seafood. For the
      Spanish population, the mean intake of total arsenic estimated on the basis of
      the results obtained in this study is 245 microg/day. The intake of inorganic
      arsenic (2.3 microg/day) represents 1.7% of the World Health Organization
      provisional tolerable weekly intake (PTWI), leaving an ample safety margin for
      this population, which has a very high consumption of seafood.

PMID- 11513722
TI  - Volatility of patulin in apple juice.
AB  - Patulin is a mycotoxin produced by certain fungi, such as those found commonly on
      apples. The patulin content of apple juice is a regulatory concern because
      patulin is a suspected carcinogen and mutagen. A simple model of the apple juice
      concentration process was carried out to examine the possible contamination of
      patulin in apple aroma, a distillate produced commercially in the concentration
      of apple juice. The results show no evidence for patulin volatility, and document
      a reduction in patulin content by at least a factor of 250 in the apple
      distillate obtained from apple juice. Furthermore, a survey of several commercial
      apple aroma samples found no evidence of patulin content.

PMID- 11513723
TI  - Development of enzyme-linked immunosorbent assays for the hepatotoxic alkaloids
      riddelliine and riddelliine N-oxide.
AB  - Pyrrolizidine alkaloid-containing plants are widely distributed throughout the
      world and are particularly common in the genus Senecio. The structural types and
      concentrations of the alkaloids vary among plant species. In addition, within a
      species of plant, concentrations vary with environment and location. Many
      pyrrolizidine alkaloids are toxic and cause poisoning in livestock and in humans.
      Rapid, sensitive, and specific diagnostic techniques are needed to identify
      poisoned animals and to determine the particular plants and conditions under
      which livestock are likely to be poisoned. In this study, two competitive
      inhibition enzyme-linked immunosorbent assays for riddelliine, riddelliine N
      oxide, and other closely related pyrrolizidine alkaloids were developed using
      polyclonal antibodies. One assay is class specific toward the free base forms of
      the pyrrolizidine alkaloids; the other assay showed cross-reactivity to both the
      free base and N-oxide forms of the alkaloids. The assay with the lowest limit of
      detection had an I(50) of 803.9 pg with a limit of detection of 47.5 pg for
      riddelliine. Spike and recovery studies for riddelliine in bovine blood ranged
      from 45 to 74%. The assay that showed cross-reactivity between the N-oxide and
      free base forms of the pyrrolizidine alkaloids allowed estimation of the total
      pyrrolizidine alkaloid content in Senecio riddellii in admixture with alfalfa.
      These findings suggest that these techniques will be excellent tools to diagnose
      poisoned animals and identify highly toxic plants.

PMID- 11513725
TI  - Early phosphoinositide 3-kinase activity is required for late activation of
      protein kinase Cepsilon in platelet-derived-growth-factor-stimulated cells:
      evidence for signalling across a large temporal gap.
AB  - At least two signalling systems have the potential to contribute to the
      activation of protein kinase C (PKC) family members such as PKCepsilon. One of
      these is phosphoinositide 3-kinase (PI 3-kinase), whose lipid products activate
      PKCepsilon in vitro and in living cells. The recent observation that there are
      multiple waves of PI 3-kinase and PKCepsilon activity within the G(0)-to-S phase
      interval provides a new opportunity to investigate the relationship between these
      two signalling enzymes in vivo. We have assessed the relative importance of the
      early and late waves of PI 3-kinase activity for the corresponding waves of
      PKCepsilon activity. Blocking the first phase of PI 3-kinase activity inhibited
      both early and late activation of PKCepsilon. In contrast, the second wave of PI
      3-kinase activity was dispensable for late activation of PKCepsilon. These
      findings suggested that early PI 3-kinase activation induced a stable change in
      PKCepsilon, which predisposed it to subsequent activation by lipid cofactors.
      Indeed, partial proteolysis of PKCepsilon indicated that early activation of PI 3
      kinase led to a conformation change in PKCepsilon that persisted as the activity
      of PKCepsilon cycled. We propose a two-step hypothesis for the activation of
      PKCepsilon in vivo. One step is stable and depends on PI 3-kinase, whereas the
      other is transient and may depend on the availability of lipid cofactors.
      Finally, these studies reveal that PI 3-kinase and PKCepsilon are capable of
      communicating over a relatively long time interval and begin to elucidate the
      mechanism.

PMID- 11513726
TI  - Crystal structure of the phosphatidylinositol 3,4-bisphosphate-binding pleckstrin
      homology (PH) domain of tandem PH-domain-containing protein 1 (TAPP1): molecular
      basis of lipid specificity.
AB  - Phosphatidylinositol 3,4,5-trisphosphate [PtdIns(3,4,5)P(3)] and its immediate
      breakdown product PtdIns(3,4)P(2) function as second messengers in growth factor-
      and insulin-induced signalling pathways. One of the ways that these 3
      phosphoinositides are known to regulate downstream signalling events is by
      attracting proteins that possess specific PtdIns-binding pleckstrin homology (PH)
      domains to the plasma membrane. Many of these proteins, such as protein kinase B,
      phosphoinositide-dependent kinase 1 and the dual adaptor for phosphotyrosine and
      3-phosphoinositides (DAPP1) interact with both PtdIns(3,4,5)P(3) and
      PtdIns(3,4)P(2) with similar affinity. Recently, a new PH-domain-containing
      protein, termed tandem PH-domain-containing protein (TAPP) 1, was described which
      is the first protein reported to bind PtdIns(3,4)P(2) specifically. Here we
      describe the crystal structure of the PtdIns(3,4)P(2)-binding PH domain of TAPP1
      at 1.4 A (1 A=0.1 nm) resolution in complex with an ordered citrate molecule. The
      structure is similar to the known structure of the PH domain of DAPP1 around the
      D-3 and D-4 inositol-phosphate-binding sites. However, a glycine residue adjacent
      to the D-5 inositol-phosphate-binding site in DAPP1 is substituted for a larger
      alanine residue in TAPP1, which also induces a conformational change in the
      neighbouring residues. We show that mutation of this glycine to alanine in DAPP1
      converts DAPP1 into a TAPP1-like PH domain that only interacts with
      PtdIns(3,4)P(2), whereas the alanine to glycine mutation in TAPP1 permits the
      TAPP1 PH domain to interact with PtdIns(3,4,5)P(3).

PMID- 11513727
TI  - Biosynthesis and intracellular post-translational processing of normal and mutant
      platelet glycoprotein GPIb-IX.
AB  - The multisubunit leucine-rich glycoprotein (GP) Ib-IX-V complex mediates von
      Willebrand factor-dependent platelet adhesion at sites of blood-vessel injury.
      Molecular defects of this receptor are reported to cause the Bernard-Soulier
      haemorrhagic disorder. To gain insight into the mechanisms controlling expression
      of normal and defective receptors, we performed pulse-chase metabolic studies and
      detailed analysis of intracellular processing in GPIb-IX-transfected Chinese
      hamster ovary cells. In the native complex, after early subunit association,
      sugars N-linked to the three subunits are trimmed and sialylated in the Golgi
      compartment and GPIbalpha undergoes extensive O-glycosylation. Surface
      biotinylation during chase demonstrated that only fully processed complexes reach
      the cell surface. Tunicamycin treatment revealed that early N-glycosylation is
      not required for O-glycosylation of GPIbalpha and surface expression of the
      complex. Biosynthetic studies were then performed on a Bernard-Soulier variant
      based on previous description of abnormal GPIbalpha size and decreased surface
      expression. The mutant complex associated normally, but displayed defective
      processing of its N-linked sugars and abnormal O-glycosylation of GPIbalpha.
      Confocal immunofluorescence microscopy revealed that the mutant complexes could
      reach the cell surface but also accumulated intracellularly, while use of
      compartment specific markers showed strong co-localization in the endoplasmic
      reticulum (ER) and ER-to-Golgi intermediate compartments ('ERGIC') and only
      slight labelling of the cis-Golgi. Blockade before the Golgi was confirmed by
      brefeldin A treatment, which restored O-glycosylation and processing of N-linked
      sugars. The present study has shown that transfer from the ER to the Golgi
      represents an important step for controlling post-translational processing and
      surface expression of normal GPIb-IX-V complex.

PMID- 11513728
TI  - Heterogeneous nuclear ribonucleoprotein E1B-AP5 is methylated in its Arg-Gly-Gly
      (RGG) box and interacts with human arginine methyltransferase HRMT1L1.
AB  - The heterogeneous nuclear ribonucleoprotein (hnRNP) family includes predominantly
      nuclear proteins acting at different stages of mRNA metabolism. A characteristic
      feature of hnRNPs is to undergo post-translational asymmetric arginine
      methylation catalysed by different type 1 protein arginine methyltransferases
      (PRMTs). A novel mammalian hnRNP, E1B-AP5, recently identified by its interaction
      with adenovirus early protein E1B-55 kDa, has been proposed to have a regulatory
      role in adenoviral and host-cell mRNA processing/nuclear export [Gabler, Schutt,
      Groitl, Wolf, Shenk and Dobner (1998) J. Virol. 72, 7960-7971]. Here we report
      that E1B-AP5 is methylated in vivo in its Arg-Gly-Gly (RGG)-box domain, known to
      mediate protein-RNA interactions. The activity responsible for E1B-AP5
      methylation forms a complex with E1B-AP5 in vivo. The predominant mammalian
      arginine methyltransferase HRMT1L2 (hPRMT1) did not detectably methylate
      endogenous E1B-AP5 despite efficiently methylating a recombinant RGG-box domain
      of E1B-AP5. Using yeast two-hybrid screening we identified HRMT1L1 (PRMT2) as one
      of the proteins interacting with E1B-AP5. By in situ immunofluorescence we
      demonstrated that E1B-AP5 co-localizes with the nuclear fraction of HRMT1L1. The
      Src homology 3 (SH3) domain of HRMT1L1 was essential for its interaction with E1B
      AP5 in vivo. We suggest that HRMT1L1 is responsible for specific E1B-AP5
      methylation in vivo.

PMID- 11513729
TI  - Inhibition of the neutrophil NADPH oxidase and associated H+ channel by diethyl
      pyrocarbonate (DEPC), a histidine-modifying agent: evidence for at least two
      target sites.
AB  - Diethyl pyrocarbonate (DEPC), a histidine-modifying reagent, has been utilized to
      demonstrate the importance of histidine residues in the functioning of proteins.
      In previous studies of the NADPH oxidase, histidine residues have been determined
      to be important in the ability of gp91(phox) to function as an H(+) pathway and
      in the binding of haem and FAD. We have investigated the ability of DEPC to
      inhibit H(+) flux and superoxide generation by human neutrophils. Proton flux
      through the NADPH oxidase-associated H(+) channel was inhibited by DEPC only if
      applied simultaneously with an activator of the channel. This suggested that the
      site modified by DEPC is not accessible in the closed channel. Superoxide
      generation by the NADPH oxidase was also inhibited by DEPC when applied after or
      simultaneously with the activator. Translocation of the NADPH oxidase cytosolic
      components, p67(phox) and p47(phox), to the membrane was unaffected by DEPC. In a
      cell-free system, DEPC-treated membranes failed to support superoxide generation
      or the reduction of Iodonitrotetrazolium Violet and showed a loss of the
      characteristic cytochrome b(558) spectrum. Superoxide generation by DEPC-treated
      cytosol was inhibited slightly. Therefore it can be concluded that there are two
      sites within the NADPH oxidase that interact with DEPC, one in the H(+) pathway,
      only accessible in the activated oxidase, and a second accessible prior to
      activation of the NADPH oxidase. The latter non-proton pathway DEPC site is
      located within the membrane components of the NADPH oxidase and is associated
      with the binding of haem in the enzyme complex.

PMID- 11513730
TI  - Suicide inactivation of xanthine oxidoreductase during reduction of inorganic
      nitrite to nitric oxide.
AB  - Xanthine oxidoreductase (XOR) is progressively inactivated while catalysing the
      reduction of inorganic nitrite to NO by xanthine. Inactivation results from
      conversion of the enzyme into its desulpho-form. The rate of inactivation
      increases with nitrite concentration. Similar behaviour was shown when NADH
      replaced xanthine as reducing substrate. A kinetic model is proposed
      incorporating a 'suicide' inactivation involving an enzyme-substrate (product)
      complex, rather than inactivation by free NO. The model provides a good fit to
      progress curves of the reaction of xanthine or NADH with nitrite in the presence
      of the oxidase or dehydrogenase forms of the enzyme. Inorganic nitrate, like
      nitrite, was shown to be reduced at the molybdenum site of XOR. With xanthine as
      reducing substrate, nitrite was produced in essentially a 1:1 stoichiometric
      ratio with respect to urate. Unlike the case of nitrite, the enzyme was not
      significantly inactivated, implying that inactivation during nitrite reduction
      depends on the presence of nascent NO in its enzyme complex.

PMID- 11513731
TI  - Semicarbazide-sensitive amine oxidase activation promotes adipose conversion of
      3T3-L1 cells.
AB  - Semicarbazide-sensitive amine oxidase (SSAO) is an amine oxidase related to the
      copper-containing amine oxidase family. The tissular form of SSAO is located at
      the plasma membrane, and is mainly expressed in vascular smooth muscle cells and
      adipocytes. Recent studies have suggested that SSAO could activate glucose
      transport in fat cells. In the present work, we investigated the potential role
      of a chronic SSAO activation on adipocyte maturation of the 3T3-L1 pre-adipose
      cell line. Exposure of post-confluent 3T3-L1 pre-adipocytes to methylamine, a
      physiological substrate of SSAO, promoted adipocyte differentiation in a time-
      and dose-dependent manner. This effect could be related to SSAO activation, since
      it was antagonized in the presence of the SSAO inhibitor semicarbazide, but not
      in the presence of the monoamine oxidase inhibitor pargyline. In addition,
      methylamine-induced adipocyte maturation was mimicked by 3T3-L1 cell treatment
      with other SSAO substrates. Finally, the large reversion of methylamine action by
      catalase indicated that hydrogen peroxide generated by SSAO was involved, at
      least in part, in the modulation of adipocyte maturation. Taken together, our
      results suggest that SSAO may contribute to the control of adipose tissue
      development.

PMID- 11513732
TI  - Concurrent overexpression of ornithine decarboxylase and spermidine/spermine N(1)
      acetyltransferase further accelerates the catabolism of hepatic polyamines in
      transgenic mice.
AB  - We have generated a hybrid transgenic mouse line overexpressing both ornithine
      decarboxylase (ODC) and spermidine/spermine N(1)-acetyltransferase (SSAT) under
      the control of the mouse metallothionein (MT) I promoter. In comparison with
      singly transgenic animals overexpressing SSAT, the doubly transgenic mice
      unexpectedly displayed much more striking signs of activated polyamine
      catabolism, as exemplified by a massive putrescine accumulation and an extreme
      reduction of hepatic spermidine and spermine pools. Interestingly, the profound
      depletion of the higher polyamines in the hybrid animals occurred in the presence
      of strikingly high ODC activity and tremendous putrescine accumulation. Polyamine
      catabolism in the doubly transgenic mice could be enhanced further by
      administration of zinc or the polyamine analogue N(1),N(11)-diethylnorspermine.
      In tracer experiments with [(14)C]spermidine we found that, in comparison with
      syngenic animals, both MT-ODC and MT-SSAT mice possessed an enhanced efflux
      mechanism for hepatic spermidine. In the MT-ODC animals this mechanism apparently
      operated in the absence of measurable SSAT activity. In the hybrid animals,
      spermidine efflux was stimulated further in comparison with the singly transgenic
      animals. In spite of a dramatic accumulation of putrescine and a profound
      reduction of the spermidine and spermine pools, only marginal changes were seen
      in the level of ODC antizyme. Even though the hybrid animals showed no liver or
      other organ-specific overt toxicity, except an early and permanent loss of hair,
      their life span was greatly reduced. These results can be understood from the
      perspective that catabolism is the overriding regulatory mechanism in the
      metabolism of the polyamines and that, even under conditions of severe depletion
      of spermidine and spermine, extremely high tissue pools of putrescine are not
      driven further to replenish the pools of the higher polyamines.

PMID- 11513734
TI  - Mutational analysis of the proteolytic domain of pregnancy-associated plasma
      protein-A (PAPP-A): classification as a metzincin.
AB  - The bioavailability of insulin-like growth factor (IGF)-I and -II is controlled
      by six IGF-binding proteins (IGFBPs 1-6). Bound IGF is not active, but
      proteolytic cleavage of the binding protein causes release of IGF. Pregnancy
      associated plasma protein-A (PAPP-A) has recently been found to cleave IGFBP-4 in
      an IGF-dependent manner. To experimentally support the hypothesis that PAPP-A
      belongs to the metzincin superfamily of metalloproteinases, all containing the
      elongated zinc-binding motif HEXXHXXGXXH (His-482-His-492 in PAPP-A), we
      expressed mutants of PAPP-A in mammalian cells. Substitution of Glu-483 with Ala
      causes a complete loss of activity, defining this motif as part of the active
      site of PAPP-A. Interestingly, a mutant with Glu-483 replaced by Gln shows
      residual activity. Known metzincin structures contain a so-called Met-turn, whose
      strictly conserved Met residue is thought to interact directly with residues of
      the active site. By further mutagenesis we provide experimental evidence that Met
      556 of PAPP-A, 63 residues from the zinc-binding motif, is located in a Met-turn
      of PAPP-A. Our hypothesis is also supported by secondary-structure prediction,
      and the ability of a 55-residue deletion mutant (d[S498-Y552]) to express and
      retain antigenecity. However, because PAPP-A differs in the features defining the
      individual established metzincin families, we suggest that PAPP-A belongs to a
      separate family. We also found that PAPP-A can undergo autocleavage, and that
      autocleaved PAPP-A is inactive. A lack of unifying elements in the sequences
      around the found cleavage sites of PAPP-A and a variant suggests steric
      regulation of substrate specificity.

PMID- 11513733
TI  - Adenine nucleotide translocator isoforms 1 and 2 are differently distributed in
      the mitochondrial inner membrane and have distinct affinities to cyclophilin D.
AB  - Different isoforms of the adenine nucleotide translocase (ANT) are expressed in a
      tissue-specific manner. It was assumed that ANT-1 and ANT-2 co-exist in every
      single mitochondrion and might be differently distributed within the membrane
      structures that constitute the peripheral inner membrane or the crista membrane.
      To discriminate between ANT originating from peripheral or from cristal inner
      membranes we made use of the fact that complexes between porin, the outer
      membrane pore protein, and the ANT can be generated. Such complexes between porin
      and the ANT in the peripheral inner membrane were induced in rat heart
      mitochondria and isolated from rat brain and kidney. Using ANT-isotype-specific
      antibodies and sequence analysis of the N-terminal end, it was discovered that
      the peripheral inner membrane contained ANT-1 and ANT-2, whereas the cristal
      membrane contained exclusively ANT-2. Cyclophilin was co-purified with the porin
      ANT complexes, whereas it was absent in the crista-derived ANT. This suggested
      that ANT-1 might have a higher affinity for cyclophilin. This specific intra
      mitochondrial distribution of the two ANT isotypes and cyclophilin D suggests
      specific functions of the peripheral and crista-forming parts of the inner
      membrane and the two ANT isotypes therein.

PMID- 11513735
TI  - Ubiquitination is essential for human cytomegalovirus US11-mediated dislocation
      of MHC class I molecules from the endoplasmic reticulum to the cytosol.
AB  - Human cytomegalovirus encodes two glycoproteins, US2 and US11, which cause rapid
      degradation of MHC class I molecules, thus preventing recognition of virus
      infected cells by the immune system. This degradation process involves retrograde
      transport or 'dislocation' of MHC class I molecules from the endoplasmic
      reticulum (ER) to the cytosol, where they are deglycosylated by an N-glycanase
      and degraded by the proteasome. At present it is unknown whether ubiquitination
      is required for US2- and US11-mediated dislocation and degradation of MHC class I
      molecules. Here, we show that in E36ts20 hamster cells, which contain a
      temperature-sensitive mutation in the E1 ubiquitin-activating enzyme, US11
      mediated degradation of MHC class I molecules is strongly impaired at the non
      permissive temperature, indicating the necessity for ubiquitination in this
      process. We next addressed the question of whether ubiquitination is a condition
      for the retrograde movement of MHC class I molecules from the ER to the cytosol,
      or whether ubiquitination is merely required for recognition of dislocated MHC
      class I molecules by the proteasome. In the absence of a functional ubiquitin
      system, complexes of US11 and MHC class I molecules accumulate in the ER. In this
      state the membrane topology of MHC class I molecules does not significantly
      change, as judged from proteinase K digestions. Thus the results indicate that a
      functional ubiquitin system is essential for dislocation of MHC class I molecules
      from the ER to the cytosol.

PMID- 11513737
TI  - Independent and synergistic interaction of retinal G-protein subunits with bovine
      rhodopsin measured by surface plasmon resonance.
AB  - We have used surface plasmon resonance (SPR) measurements for the kinetic
      analysis of G-protein-receptor interaction monitored in real time. Functionally
      active rhodopsin was immobilized on an SPR surface, with full retention of
      biochemical specific activity for catalysis of nucleotide exchange on the retinal
      G-protein alpha subunit, via binding to immobilized concanavalin A. The binding
      interactions of bovine retinal alpha(t) and beta(1)gamma(1) subunits with
      rhodopsin measured by SPR were profoundly synergistic. Synergistic binding of the
      retinal G-protein subunits to rhodopsin was not observed for guanosine 5'-[gamma
      thio]triphosphate-bound Galpha(t), nor was binding observed with squid retinal
      Galpha(q), which is not activated by bovine rhodopsin. The binding affinity
      (336+/-171 nM; mean value+/-S.D.) of retinal betagamma for rhodopsin in the
      presence of retinal alpha subunit measured by SPR confirmed the apparent affinity
      of 254 nM determined previously by nucleotide exchange assays. Binding of
      beta(1)gamma(1), beta(1)gamma(2), and beta(1)gamma(8-olf) dimers to rhodopsin,
      independently of the alpha subunit, was readily observable by SPR. Further, these
      dimers, differing only in their gamma subunit compositions, displayed markedly
      distinct binding affinities and kinetics. The beta(1)gamma(2) dimer bound with a
      kinetically determined K(d) of 13+/-3 nM, a value nearly identical with the
      biochemically determined K(1/2) of 10 nM. The physiologically appropriate
      beta(1)gamma(1) displayed rapid association and dissociation kinetics, whereas
      the other beta(1)gamma dimers dissociated at a rate less than 1/100 as fast. Thus
      rhodopsin interaction with its native signalling partners is both rapid and
      transient, whereas the interaction of rhodopsin with heterologous Gbetagamma
      dimers is markedly prolonged. These results suggest that the duration of a G
      protein-coupled receptor signalling event is an intrinsic property of the G
      protein coupling partners; in particular, the betagamma dimer.

PMID- 11513736
TI  - Evidence for a novel natriuretic peptide receptor that prefers brain natriuretic
      peptide over atrial natriuretic peptide.
AB  - Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) exert their
      physiological actions by binding to natriuretic peptide receptor A (NPRA), a
      receptor guanylate cyclase (rGC) that synthesizes cGMP in response to both
      ligands. The family of rGCs is rapidly expanding, and it is plausible that there
      might be additional, as yet undiscovered, rGCs whose function is to provide
      alternative signalling pathways for one or both of these peptides, particularly
      given the low affinity of NPRA for BNP. We have investigated this hypothesis,
      using a genetically modified (knockout) mouse in which the gene encoding NPRA has
      been disrupted. Enzyme assays and NPRA-specific Western blots performed on
      tissues from wild-type mice demonstrate that ANP-activated cGMP synthesis
      provides a good index of NPRA protein expression, which ranges from maximal in
      adrenal gland, lung, kidney, and testis to minimal in heart and colon. In
      contrast, immunoreactive NPRA is not detectable in tissues isolated from NPRA
      knockout animals and ANP- and BNP-stimulatable GC activities are markedly reduced
      in all mutant tissues. However, testis and adrenal gland retain statistically
      significant, high-affinity responses to BNP. This residual response to BNP cannot
      be accounted for by natriuretic peptide receptor B, or any other known mammalian
      rGC, suggesting the presence of a novel receptor in these tissues that prefers
      BNP over ANP.

PMID- 11513738
TI  - Kinetic competence of the cADP-ribose-CD38 complex as an intermediate in the
      CD38/NAD+ glycohydrolase-catalysed reactions: implication for CD38 signalling.
AB  - CD38/NAD(+) glycohydrolase is a type II transmembrane glycoprotein widely used to
      study T- and B-cell activation and differentiation. CD38 is endowed with two
      different activities: it is a signal transduction molecule and an ectoenzyme that
      converts NAD(+) into ADP-ribose (NAD(+) glycohydrolase activity) and small
      proportions of cADP-ribose (cADPR; ADP-ribosyl cyclase activity), a calcium
      mobilizing metabolite, which, ultimately, can also be hydrolysed (cADPR hydrolase
      activity). The relationship between these two properties, and strikingly the
      requirement for signalling in the formation of free or enzyme-complexed cADPR, is
      still ill-defined. In the present study we wanted to test whether the CD38-cADPR
      complex is kinetically competent in the conversion of NAD(+) into the reaction
      product ADP-ribose. In principle, such a complex could be invoked for cross-talk,
      via conformational changes, with neighbouring partner(s) of CD38 thus triggering
      the signalling phenomena. Analysis of the kinetic parameters measured for the
      CD38/NAD(+) glycohydrolase-catalysed hydrolysis of 2'-deoxy-2'-aminoribo-NAD(+)
      and ADP-cyclo[N1,C1']-2'-deoxy-2'-aminoribose (slowly hydrolysable analogues of
      NAD(+) and cADPR respectively) ruled out that the CD38-cADPR complex can
      accumulate under steady-state conditions. This was borne out by simulation of the
      prevalent kinetic mechanism of CD38, which involve the partitioning of a common
      E.ADP-ribosyl intermediate in the formation of the enzyme-catalysed reaction
      products. Using this mechanism, microscopic rate conditions were found which
      transform a NAD(+) glycohydrolase into an ADP-ribosyl cyclase. Altogether, the
      present work shows that if the cross-talk with a partner depends on a
      conformational change of CD38, this is most probably not attributable to the
      formation of the CD38-cADPR complex. In line with recent results on the
      conformational change triggered by CD38 ligands [Berthelier, Laboureau, Boulla,
      Schuber and Deterre (2000) Eur. J. Biochem. 267, 3056-3064], we believe that the
      Michaelis CD38-NAD(+) complex could play such a role instead.

PMID- 11513739
TI  - Cell-cycle-dependent association of protein phosphatase 1 and focal adhesion
      kinase.
AB  - Immunofluorescence studies with protein phosphatase-1 (PP1) isoforms-specific
      antibodies detected PP1delta, but not alpha or gamma1, at focal adhesions.
      PP1delta also co-immunoprecipitated with the focal adhesion kinase (FAK) and the
      alphav-integrin. In the present study glutathione S-transferase (GST)-PP1delta
      pulled-down FAK from fibroblasts extract and the interaction domain localized
      between residues 159 and 295 of delta. The association was confirmed by the
      ability to GST-FAK-related non-kinase (FRNK) to pull-down PP1delta from
      fibroblasts extract. GST-FRNK also pulled-down purified muscle PP1 catalytic
      subunit, thus indicating direct interaction between FAK and PP1. FAK displays
      consensus sequences for phosphorylation by cell division cycle kinase-2-cyclin B,
      and might be a PP1 substrate. In fact, FAK immunoprecipitated from metabolically
      labelled mitotic HeLa cells without tyrosine phosphatase inhibitors was
      phosphorylated on Ser only and was dephosphorylated in vitro by purified muscle
      PP1, with loss of phospho-Ser. No PP1 was associated with FAK immunoprecipitated
      from mitotic HeLa cells. However, progressively more PP1 activity was assayed in
      FAK-immunoprecipitates obtained from cells released from mitosis. The associated
      activity was maximal at 2 h from the mitotic release (when 85-90% of the cells
      remained round) and decreased to basal level by 8 h (when cells were all
      polygonal). At the same time FAK underwent dephosphorylation, which was completed
      by 4 h. FAK obtained from cells at 1.5 h was Ser-phosphorylated, and underwent
      dephosphorylation during in vitro incubation, with loss of phospho-Ser,
      indicating the presence of active FAK-bound phosphatase. The only FAK-associated
      PP1 isoform between 1 and 8 h was PP1delta. The results suggest that FAK
      dephosphorylation by PP1delta occurs in cells released from mitosis, and
      confirmed the specific association of PP1delta, as detected previously in
      adherent cells.

PMID- 11513740
TI  - A role for smooth endoplasmic reticulum membrane cholesterol ester in determining
      the intracellular location and regulation of sterol-regulatory-element-binding
      protein-2.
AB  - Cellular cholesterol homoeostasis is regulated through proteolysis of the
      membrane-bound precursor sterol-regulatory-element-binding protein (SREBP) that
      releases the mature transcription factor form, which regulates gene expression.
      Our aim was to identify the nature and intracellular site of the putative sterol
      regulatory pool which regulates SREBP proteolysis in hamster liver. Cholesterol
      metabolism was modulated by feeding hamsters control chow, or a cholesterol
      enriched diet, or by treatment with simvastatin or with the oral acyl
      CoA:cholesterol acyltransferase inhibitor C1-1011 plus cholesterol. The effects
      of the different treatments on SREBP activation were confirmed by determination
      of the mRNAs for the low-density lipoprotein receptor and hydroxymethylglutaryl
      CoA (HMG-CoA) reductase and by measurement of HMG-CoA reductase activity. The
      endoplasmic reticulum was isolated from livers and separated into subfractions by
      centrifugation in self-generating iodixanol gradients. Immunodetectable SREBP-2
      accumulated in the smooth endoplasmic reticulum of cholesterol-fed animals.
      Cholesterol ester levels of the smooth endoplasmic reticulum membrane (but not
      the cholesterol levels) increased after cholesterol feeding and fell after
      treatment with simvastatin or C1-1011. The results suggest that an increased
      cellular cholesterol load causes accumulation of SREBP-2 in the smooth
      endoplasmic reticulum and, therefore, that membrane cholesterol ester may be one
      signal allowing exit of the SREBP-2/SREBP-cleavage-regulating protein complex to
      the Golgi.

PMID- 11513741
TI  - Glycosylation by Pichia pastoris decreases the affinity of a family 2a
      carbohydrate-binding module from Cellulomonas fimi: a functional and mutational
      analysis.
AB  - When produced by Pichia pastoris, three of the five Asn-Xaa-Ser/Thr sequences
      (corresponding to Asn-24, Asn-73 and Asn-87) in the carbohydrate-binding module
      CBM2a of xylanase 10A from Cellulomonas fimi are glycosylated. The glycans are of
      the high-mannose type, ranging in size from GlcNAc(2)Man(8) to GlcNAc(2)Man(14).
      The N-linked glycans block the binding of CBM2a to cellulose. Analysis of mutants
      of CBM2a shows that glycans on Asn-24 decrease the association constant (K(a))
      for the binding of CBM2a to bacterial microcrystalline cellulose approx. 10-fold,
      whereas glycans on Asn-87 destroy binding. The K(a) of a mutant of CBM2a lacking
      all three N-linked glycosylation sites is the same when the polypeptide is
      produced by either Escherichia coli or P. pastoris and is approx. half that of
      wild-type CBM2a produced by E. coli.

PMID- 11513742
TI  - Colony-stimulating factor-1 (CSF-1) receptor-mediated macrophage differentiation
      in myeloid cells: a role for tyrosine 559-dependent protein phosphatase 2A (PP2A)
      activity.
AB  - M1 myeloid cells transfected with the wild-type (WT) colony-stimulating factor-1
      (CSF-1) receptor (CSF-1R; M1/WT cells) undergo CSF-1-dependent macrophage
      differentiation. By mutation studies, we have provided prior evidence that
      tyrosine 559 in the CSF-1R cytoplasmic domain governs the Src-dependent
      differentiation pathway. Further components of this pathway were then sought. We
      report that the extent of CSF-1-mediated tyrosine phosphorylation of protein
      phosphatase 2A (PP2A), and the associated loss of its activity were reduced in M1
      cells transfected with the CSF-1R with a tyrosine-to-phenylalanine mutation at
      position 559 (M1/559 cells), compared with the corresponding responses in CSF-1
      treated M1/WT cells. This evidence for an involvement of a reduction in PP2A
      activity in the differentiation process was supported by the restoration of the
      defect in the CSF-1-mediated differentiation of M1/559 cells by the addition of
      the PP2A inhibitor, okadaic acid. It was also found that the degree of activation
      of extracellular-signal-regulated kinase (ERK) activities by CSF-1 was reduced in
      M1/559 cells, suggesting their involvement in the differentiation process. These
      data suggest that PP2A and ERK form part of the Src-dependent signal-transduction
      cascade governing CSF-1-mediated macrophage differentiation in M1 cells.

PMID- 11513743
TI  - Analysis of sucrose accumulation in the sugar cane culm on the basis of in vitro
      kinetic data.
AB  - Sucrose accumulation in developing sugar cane (Saccharum officinarum) is
      accompanied by a continuous synthesis and cleavage of sucrose in the storage
      tissues. Despite numerous studies, the factors affecting sucrose accumulation are
      still poorly understood, and no consistent pattern has emerged which pinpoints
      certain enzyme activities as important controlling steps. Here, we develop an
      approach based on pathway analysis and kinetic modelling to assess the
      biochemical control of sucrose accumulation and futile cycling in sugar cane. By
      using the concept of elementary flux modes, all possible routes of futile cycling
      of sucrose were enumerated in the metabolic system. The available kinetic data
      for the pathway enzymes were then collected and assembled in a kinetic model of
      sucrose accumulation in sugar cane culm tissue. Although no data were fitted, the
      model agreed well with independent experimental results: in no case was the
      difference between calculated and measured fluxes and concentrations greater than
      2-fold. The model thus validated was then used to assess different enhancement
      strategies for increasing sucrose accumulation. First, the control coefficient of
      each enzyme in the system on futile cycling of sucrose was calculated. Secondly,
      the activities of those enzymes with the numerically largest control coefficients
      were varied over a 5-fold range to determine the effect on the degree of futile
      cycling, the conversion efficiency from hexoses into sucrose, and the net sucrose
      accumulation rate. In view of the modelling results, overexpression of the
      fructose or glucose transporter or the vacuolar sucrose import protein, as well
      as reduction of cytosolic neutral invertase levels, appear to be the most
      promising targets for genetic manipulation. This offers a more directed
      improvement strategy than cumbersome gene-by-gene manipulation. The kinetic model
      can be viewed and interrogated on the World Wide Web at
      http://jjj.biochem.sun.ac.za.

PMID- 11513745
TI  - Biochemical characterization of the beta-1,4-glucuronosyltransferase GelK in the
      gellan gum-producing strain Sphingomonas paucimobilis A.T.C.C. 31461.
AB  - Biosynthesis of bacterial polysaccharide-repeat units proceeds by sequential
      transfer of sugars, from the appropriate sugar donor to an activated lipid
      carrier, by committed glycosyltransferases (GTs). Few studies on the mechanism of
      action for this type of GT are available. Sphingomonas paucimobilis A.T.C.C.
      31461 produces the industrially important polysaccharide gellan gum. We have
      cloned the gelK gene from S. paucimobilis A.T.C.C. 31461. GelK belongs to family
      1 of the GT classification [Campbell, Davies, Bulone, Henrissat (1997) Biochem.
      J. 326, 929-939]. Sequence similarity studies suggest that GelK consists of two
      protein modules corresponding to the -NH(2) and -CO(2)H halves, the latter
      possibly harbouring the GT activity. The gelK gene and the open reading frames
      coding for the -NH(2) (GelK(NH2)) and -CO(2)H (GelK(COOH)) halves were
      overexpressed in Escherichia coli. GelK and GelK(NH2) were present in both the
      soluble and membrane fractions of E. coli, whereas GelK(COOH) was only present in
      the soluble fraction. GelK catalysed the transfer of [(14)C]glucuronic acid from
      UDP-[(14)C]glucuronic acid into a glycolipid extracted from S. paucimobilis or E.
      coli, even in the presence of EDTA, and the radioactive sugar was released from
      the glycolipid by beta-1,4-glucuronidase. GelK was not able to use synthetic
      glucosyl derivatives as acceptors, indicating that the PP(i)-lipid moiety is
      needed for enzymic activity. Recombinant GelK(NH2) and GelK(COOH) did not show
      detectable activity. Based on the biochemical characteristics of GelK and on
      sequence similarities with N-acetylglucosaminyltransferase, we propose that GT
      families 1 and 28 form a superfamily.

PMID- 11513744
TI  - Subnuclear localization and mitotic phosphorylation of HIRA, the human homologue
      of Saccharomyces cerevisiae transcriptional regulators Hir1p/Hir2p.
AB  - The HIRA gene encodes a nuclear protein with histone-binding properties that have
      been conserved from yeast to humans. Hir1p and Hir2p, the two HIRA homologues in
      Saccharomyces cerevisiae, are transcriptional co-repressors whose action resides
      at the chromatin level and occurs in a cell-cycle-regulated fashion. In mammals,
      HIRA is an essential gene early during development, possibly through the control
      of specific gene-transcription programmes, but its exact function remains to be
      deciphered. Here we report on the subnuclear distribution and cell-cycle
      behaviour of the HIRA protein. Using both biochemical and immunofluorescence
      techniques, a minor fraction of HIRA was found tightly associated with the
      nuclear matrix, the material that remains after nuclease treatment and high-salt
      extraction. However, most HIRA molecules proved extractable. In non-synchronized
      cell populations, extraction from chromatin necessitated 300 mM NaCl whereas 150
      mM was sufficient in mitotic cells. Immunofluorescence staining and microscopic
      examination of mitotic cells revealed HIRA as excluded from condensed
      chromosomes, confirming a lack of association with chromatin during mitosis.
      Western-blot analysis indicated that HIRA molecules were hyper-phosphorylated at
      this point in the cell cycle. Metabolic labelling and pulse-chase experiments
      characterized HIRA as a stable protein with a half-life of approx. 12 h. The
      mitotic phosphorylation of HIRA could provide the dividing cell with a way to
      retarget HIRA-containing multi-protein complexes to different chromatin regions
      in daughter compared with parental cells.

PMID- 11513746
TI  - Direct identification of a major autophosphorylation site on vascular endothelial
      growth factor receptor Flt-1 that mediates phosphatidylinositol 3'-kinase
      binding.
AB  - Progress has been made in our understanding of the mechanism by which the binding
      of vascular endothelial growth factor (VEGF) to cognate receptors induces a range
      of biological responses, but it is far from complete. Identification of receptor
      autophosphorylation sites will allow us to determine how activated VEGF receptors
      are coupled to specific downstream signalling proteins. In the present study, we
      have expressed human VEGF receptors in insect cells using the baculovirus
      expression system, identified a major autophosphorylation site on the VEGF
      receptor fms-like tyrosine kinase-1 (Flt-1) by HPLC-electrospray ionization (ESI)
      MS, and characterized in vitro interactions between Flt-1 and
      phosphatidylinositol 3'-kinase (PI3-kinase). Infection of High 5 insect cells
      with Flt-1 recombinant virus resulted in the expression of a 170 kDa
      glycoprotein, which bound VEGF with a K(d) of 2 x 10(-10) M in intact insect
      cells. The overexpressed recombinant Flt-1 receptors exhibited tyrosine kinase
      activity and were constitutively phosphorylated. Analysis of Flt-1 tryptic
      peptides by HPLC-ESI-MS with selective phosphate ion monitoring identified a
      hexapeptide (YVNAFK; where single-letter amino-acid code has been used)
      containing a phosphotyrosine (pTyr) residue at position 1213. Using synthetic
      phosphopeptides, this pTyr residue was found to be directly involved in the
      binding of PI3-kinase in vitro even though it did not fall within a consensus
      pYM/VXM PI3-kinase binding motif. These results suggest that phosphorylated Flt-1
      associates with PI3-kinase at pTyr(1213) to mediate the activation of this
      pathway in VEGF signalling.

PMID- 11513747
TI  - Regulation of SulA cleavage by Lon protease by the C-terminal amino acid of SulA,
      histidine.
AB  - SulA protein, a cell division inhibitor in Escherichia coli, is degraded by Lon
      protease. The C-terminal eight residues of SulA have been shown to be recognized
      by Lon; however, it remains to be elucidated which amino acid in the C-terminus
      of SulA is critical for the recognition of SulA by Lon. To clarify this point, we
      constructed mutants of SulA with changes in the C-terminal residues, and examined
      the accumulation and stability of the resulting mutant SulA proteins in vivo.
      Substitution of the extreme C-terminal histidine residue with another amino acid
      led to marked accumulation and high stability of SulA in lon(+) cells. A SulA
      mutant in which the C-terminal eight residues were deleted (SulAC161) showed high
      accumulation and stability, but the addition of histidine to the C-terminus of
      SulAC161 (SulAC161+H) made it labile. Similarly, SulAC161+H fused to maltose
      binding protein (MBP-SulAC161+H) formed a tight complex with and was degraded
      rapidly by Lon in vitro. Histidine competitively inhibited the degradation of MBP
      SulA by Lon, while other amino acids did not. These results suggest that the
      histidine residue at the extreme C-terminus of SulA is recognized specifically by
      Lon, leading to a high-affinity interaction between SulA and Lon.

PMID- 11513748
TI  - Phosphoinositide 3-kinase accelerates necrotic cell death during hypoxia.
AB  - Using H9c2 cells derived from rat cardiomyocytes, we investigated the mechanism
      of cell death during hypoxia in the presence of serum and glucose. Hypoxic cell
      death is by necrosis and is accompanied by metabolic acidosis. Moreover, hypoxic
      cell death is inhibited by Hepes buffer as well as by 2-deoxyglucose, an
      inhibitor of glycolysis, indicating that metabolic acidosis should play an
      essential role in hypoxic injury. The involvement of phosphoinositide 3-kinase
      (PI 3-kinase), which is known to activate glucose metabolism, was examined using
      its inhibitor, LY290042, or adenovirus-mediated gene transfer. Hypoxic cell death
      was inhibited by LY294002 in a dose-dependent manner. Overexpression of dominant
      negative PI 3-kinase was found to reduce cell death, whereas wild-type PI 3
      kinase enhanced it. Dominant negative PI 3-kinase also reduced glucose
      consumption and acidosis, but this was stimulated by wild-type PI 3-kinase. The
      data indicate that PI 3-kinase stimulates cell death by enhancing metabolic
      acidosis. LY294002 significantly reduced glucose uptake, showing that PI 3-kinase
      regulates glycolysis at the step of glucose transport. These findings indicate
      the pivotal role of glucose metabolism in hypoxic cell death, and reveal a novel
      death-promoting effect of PI 3-kinase during hypoxia, despite this enzyme being
      considered to be a survival-promoting factor.

PMID- 11513749
TI  - c-Jun N-terminal kinase-interacting protein 1 inhibits gene expression in
      response to hypertrophic agonists in neonatal rat ventricular myocytes.
AB  - G(q)-coupled receptor agonists, such as endothelin-1 (ET-1) and phenylephrine
      (PE), initiate a hypertrophic response in cardiac myocytes that is characterized
      by increased expression of atrial natriuretic factor (ANF), beta-myosin heavy
      chain (beta-MHC), skeletal muscle alpha-actin (SkalphaA) and ventricular myosin
      light chain-2 (vMLC2). ET-1 and PE activate both the extracellular signal
      regulated kinases and c-Jun N-terminal kinases (JNKs) in cardiac myocytes, but
      the extent to which each contributes to the hypertrophic response is uncertain.
      Here we have used the JNK-binding domain of JNK-interacting protein 1 (JIP-1), a
      cytosolic scaffold protein that binds to JNK and inhibits its signalling when
      overexpressed, to assess the contribution of JNK activation to the hypertrophic
      response. Expression of JIP-1 inhibited the increase in ANF, beta-MHC, SkalphaA
      and vMLC2 reporter gene expression in response to ET-1 (by 45-86%) and PE (by 56
      60%). However, activation of these reporter genes by PMA, which does not activate
      JNK significantly in myocytes, was much less affected by overexpression of JIP-1.
      JIP-1 also failed to inhibit reporter gene activation in response to
      constitutively active Ras or Raf, but attenuated reporter gene activation induced
      by a constitutively active mutant of mitogen-activated protein kinase kinase
      kinase 1 (MEKK1), an upstream kinase that preferentially activates JNKs, by 50%.
      Overexpression of JIP-1 also significantly reduced the increase in cell area in
      response to PE from 63% to 56%, but had no effect on the increase in cell size in
      response to ET-1 (38%). These results suggest that activation of the JNK pathway
      contributes to the transcriptional and morphological responses to G(q) receptor
      coupled hypertrophic agonists.

PMID- 11513750
TI  - Glucose exerts a permissive effect on the regulation of the initiation factor 4E
      binding protein 4E-BP1.
AB  - The eukaryotic initiation factor 4E (eIF4E) binding protein (4E-BP1) interacts
      directly with eIF4E and prevents it from forming initiation factor (eIF4F)
      complexes required for the initiation of cap-dependent mRNA translation. Insulin
      and other agents induce the phosphorylation of 4E-BP1 at multiple sites,
      resulting in its release from eIF4E, and this involves signalling through the
      mammalian target of rapamycin (mTOR). Here we show that D-glucose promotes the
      ability of insulin to bring about the phosphorylation of 4E-BP1 and the formation
      of eIF4F complexes. This appears to involve facilitation of the phosphorylation
      of at least three phosphorylation sites on 4E-BP1, i.e. Thr-36, Thr-45 and Thr
      69. Non-metabolizable glucose analogues cannot substitute for D-glucose, but
      other hexoses can. This suggests that a product of hexose metabolism mediates the
      permissive effect of glucose. The effect of glucose was concentration-dependent
      within the range 1-5 mM. In contrast with the situation for 4E-BP1, glucose does
      not allow full activation of the 70 kDa ribosomal protein S6 kinase (p70 S6k;
      another target of mTOR signalling) or phosphorylation, in vivo, of its substrate,
      ribosomal protein S6. Taken together with earlier data showing that amino acids
      regulate 4E-BP1 and p70 S6k, the present findings show that 4E-BP1 in particular
      is regulated in response to the availability of both amino acids and sugars.

PMID- 11513751
TI  - Local and spatial factors determining HIV-1 protease substrate recognition.
AB  - Insertional mutagenesis of the Escherichia coli thymidylate synthase (TS) was
      used to address substrate recognition of HIV-1 protease in a well characterized
      structural context. By modifying the TS conformation while maintaining its
      enzymic activity, we investigated the influence of protein folding on protease
      substrate recognition. A slight destabilization of the TS structure permitted the
      cleavage of a target site, which was resistant in the native TS. This result
      supports a dynamic interpretation of HIV-1 protease specificity. Exposure time of
      the potential cleavage site, which depends on the stability of the global
      conformation, must be compatible with the cleavage kinetics, which are determined
      by the local sequence. Cleavage specificity has been described as the consequence
      of cumulative interactions, globally favourable, between at least six amino acids
      around the cleavage site. To investigate influence of local sequence, we
      introduced insertions of variable lengths in two exposed loops of the TS. In both
      environments, insertion of only two amino acids could determine specific
      cleavage. We then inserted libraries of dipeptides naturally cleaved by the HIV-1
      protease in order to assess the limitations of established classifications of
      substrates in different conformational contexts.

PMID- 11513752
TI  - Functional interactions between arginine-133 and aspartate-88 in the human
      reduced folate carrier: evidence for a charge-pair association.
AB  - The human reduced folate carrier (hRFC) is an integral membrane protein that
      mediates cellular uptake of reduced folates and antifolates. hRFC contains
      several highly conserved charged residues predicted to lie in the transmembrane
      domains (TMDs). To explore the possible roles of the conserved arginine-133,
      located in TMD 4, in hRFC structure and function, this residue was systematically
      mutagenized to histidine, leucine, lysine and glutamate. When transfected into
      transport-impaired K562 cells, the mutant hRFC constructs were expressed at high
      levels; however, only lysine-133 hRFC was able to transport methotrexate and (6S)
      5-formyl tetrahydrofolate. Substitution of aspartate-453 (in hRFC TMD 12) by
      valine largely preserved transport activity for both substrates. Although
      mutagenesis of aspartate-88 (in TMD 2) to leucine completely abolished transport
      activity in transfected cells, substitution with a glutamate preserved low levels
      ( approximately 12%) of transport. To assess the possibility that arginine-133
      and aspartate-88 may form a charge-pair to stabilize hRFC tertiary structure,
      both charges were neutralized (by substituting leucine and valine, respectively)
      in the same construct. In contrast to the singly mutated hRFCs, the double mutant
      exhibited high levels of transport with both methotrexate and 5-formyl
      tetrahydrofolate. These results strongly suggest that arginine-133 and aspartate
      88 form a charge-pair and that TMD 4 lies next to TMD 2 in the hRFC tertiary
      structure.

PMID- 11513753
TI  - Targeting of GLUT6 (formerly GLUT9) and GLUT8 in rat adipose cells.
AB  - The subcellular targeting of the two recently cloned novel mammalian glucose
      transporters, GLUT6 [previously referred to as GLUT9 [Doege, Bocianski, Joost and
      Schurmann (2000) Biochem. J. 350, 771-776] and GLUT8, was analysed by expression
      of haemagglutinin (HA)-epitope-tagged GLUTs in transiently transfected primary
      rat adipose cells. Similar to HA-GLUT4, both transporters, HA-GLUT6 and HA-GLUT8,
      were retained in intracellular compartments in non-stimulated cells. In contrast,
      mutation of the N-terminal dileucine motifs in both constructs led to
      constitutive expression of the proteins on the plasma membrane. Likewise, when
      endocytosis was blocked by co-expression of a dominant-negative mutant of the
      dynamin GTPase, wild-type HA-GLUT6 and HA-GLUT8 accumulated on the cell surface.
      However, in contrast with HA-GLUT4, no translocation of HA-GLUT6 and HA-GLUT8 to
      the plasma membrane was observed when the cells were stimulated with insulin,
      phorbol ester or hyperosmolarity. Thus GLUT6 and GLUT8 appear to recycle in a
      dynamin-dependent manner between internal membranes and the plasma membrane in
      rat adipose cells, but are unresponsive to stimuli that induce translocation of
      GLUT4.

PMID- 11513754
TI  - Age-related changes in the sulphation of the chondroitin sulphate linkage region
      from human articular cartilage aggrecan.
AB  - The chondroitin sulphate (CS) linkage regions have been isolated from human
      articular cartilage aggrecan (from 10- to 72-year-olds) by chondroitin ABC
      endolyase digestion and size-exclusion chromatography. Linkage region
      hexasaccharides have been characterized and their abundance estimated by high-pH
      anion-exchange chromatography. The basic structure for the CS linkage region
      oligosaccharides identified from human aggrecan is as follows: DeltaUA(beta1
      3)GalNAc[0S/4S/6S](beta1-4)GlcA(beta1-3)Gal[0S/6S](beta1-3)Gal(beta1-4)Xyl, where
      DeltaUA represents 4,5-unsaturated hexuronic acid, 4S and 6S represent an O-ester
      sulphate group on C-4 and C-6 respectively, and 0S represents zero sulphation.
      There are significant age-related changes in the abundance of the various N
      acetylgalactosamine (GalNAc) sulphation forms identified, occurring up to approx.
      20 years old. During the period from 10 to 20 years old the level of GalNAc 6
      sulphation at the linkage region increases from approx. 43% to approx. 75%, while
      there is a corresponding reduction in unsulphated (approx. 30% to approx. 20%)
      and 4-sulphated (approx. 25% to approx. 6%) GalNAc residues. There is also an
      increase in the incidence of linkage region galactose 6-sulphation (approx. 2% to
      approx. 10%) which was only observed in linkage regions with GalNAc 6-sulphation.
      Beyond 20 years old there are few changes in the relative abundance of these
      GalNAc sulphation variants; however, there is a slight increase in the abundance
      of 6-sulphation between approx. 20 years old and approx. 40 years old and a
      slight decrease in its abundance beyond approx. 40 years old. Our data show that
      in the majority of chains from tissues of all ages the GalNAc residue closest to
      the linkage region is 6-sulphated, but the level of GalNAc 6-sulphation within
      the linkage region is lower than the average level observed within the repeat
      region.

PMID- 11513755
TI  - Gene targeting in mosquito cells: a demonstration of 'knockout' technology in
      extrachromosomal gene arrays.
AB  - BACKGROUND: Gene targeting would offer a number of advantages over current
      transposon-based strategies for insect transformation. These include freedom from
      both position effects associated with quasi-random integration and concerns over
      transgene instability mediated by endogenous transposases, independence from
      phylogenetic restrictions on transposon mobility and the ability to generate gene
      knockouts. RESULTS: We describe here our initial investigations of gene targeting
      in the mosquito. The target site was a hygromycin resistance gene, stably
      maintained as part of an extrachromosomal array. Using a promoter-trap strategy
      to enrich for targeted events, a neomycin resistance gene was integrated into the
      target site. This resulted in knockout of hygromycin resistance concurrent with
      the expression of high levels of neomycin resistance from the resident promoter.
      PCR amplification of the targeted site generated a product that was specific to
      the targeted cell line and consistent with precise integration of the neomycin
      resistance gene into the 5' end of the hygromycin resistance gene. Sequencing of
      the PCR product and Southern analysis of cellular DNA subsequently confirmed this
      molecular structure. CONCLUSIONS: These experiments provide the first
      demonstration of gene targeting in mosquito tissue and show that mosquito cells
      possess the necessary machinery to bring about precise integration of exogenous
      sequences through homologous recombination. Further development of these
      procedures and their extension to chromosomally located targets hold much promise
      for the exploitation of gene targeting in a wide range of medically and
      economically important insect species.

PMID- 11513756
TI  - Physicians' preference values for hepatitis C health states and antiviral
      therapy: a survey.
AB  - BACKGROUND: Physicians' perspectives regarding hepatitis C shape their approach
      to patient management. We used utility analysis to evaluate physicians'
      perceptions of hepatitis C-related health states (HS) and their threshold to
      recommend treatment. METHODS: A written questionnaire was administered to
      practicing physicians. They were asked to rate hepatitis C health states on a
      visual analog scale ranging from 0% (death) to 100% (health without hepatitis C).
      Physicians then judged quality of life associated with the side effects of
      antiviral therapy for hepatitis C and indicated the sustained virological
      response rate that they would require to recommend treatment. RESULTS: One
      hundred and thirteen physicians from five states were included. Median utility
      ratings for hepatitis C health states declined significantly with increasing
      severity of symptoms: HS1-No Symptoms, No Cirrhosis (88%; 12% reduction from good
      health), HS2-Mild Symptoms, No Cirrhosis (66%), HS3-Moderate Symptoms, No
      Cirrhosis (49%), HS4-Mild Symptoms, Cirrhosis (40%), HS5-Severe Symptoms,
      Cirrhosis (18%) [p < 0.001]. The median rating for life with side effects of
      antiviral therapy was 47%, suggesting a 53% reduction from good health. That was
      similar to the utility value for HS3-Moderate Symptoms, No Cirrhosis. The median
      threshold value for recommending treatment was a sustained response rate of 60%.
      CONCLUSIONS: 1) Physicians' utility ratings for hepatitis C health states were
      inversely related to the severity of disease manifestations described. 2)
      Physicians viewed side effects of therapy unfavorably and indicated that on
      average, they would require a 60% sustained response rate before recommending
      treatment, which far exceeds the efficacy of current antiviral therapy for
      hepatitis C in the majority of patients.

PMID- 11513757
TI  - Dopaminergic neurons in the brain and dopaminergic innervation of the albumen
      gland in mated and virgin helisoma duryi (mollusca: pulmonata).
AB  - BACKGROUND: Dopamine was shown to stimulate the perivitelline fluid secretion by
      the albumen gland. Even though the albumen gland has been shown to contain
      catecholaminergic fibers and its innervation has been studied, the type of
      catecholamines, distribution of fibers and the precise source of this neural
      innervation has not yet been deduced. This study was designed to address these
      issues and examine the correlation between dopamine concentration and the sexual
      status of snails. RESULTS: Dopaminergic neurons were found in all ganglia except
      the pleural and right parietal, and their axons in all ganglia and major nerves
      of the brain. In the albumen gland dopaminergic axons formed a nerve tract in the
      central region, and a uniform net in other areas. Neuronal cell bodies were
      present in the vicinity of the axons. Dopamine was a major catecholamine in the
      brain and the albumen gland. No significant difference in dopamine quantity was
      found when the brain and the albumen gland of randomly mating, virgin and first
      time mated snails were compared. CONCLUSIONS: Our results represent the first
      detailed studies regarding the catecholamine innervation and quantitation of
      neurotransmitters in the albumen gland. In this study we localized
      catecholaminergic neurons and axons in the albumen gland and the brain,
      identified these neurons and axons as dopaminergic, reported monoamines present
      in the albumen gland and the brain, and compared the dopamine content in the
      brain and the albumen gland of randomly mating, virgin and first time mated
      snails.

PMID- 11513758
TI  - Systematic reviews of complementary therapies - an annotated bibliography. Part
      1: acupuncture.
AB  - BACKGROUND: Complementary therapies are widespread but controversial. We aim to
      provide a comprehensive collection and a summary of systematic reviews of
      clinical trials in three major complementary therapies (acupuncture, herbal
      medicine, homeopathy). This article is dealing with acupuncture. Potentially
      relevant reviews were searched through the register of the Cochrane Complementary
      Medicine Field, the Cochrane Library, Medline, and bibliographies of articles and
      books. To be included articles had to review prospective clinical trials of
      acupuncture; had to describe review methods explicitly; had to be published; and
      had to focus on treatment effects. Information on conditions, interventions,
      methods, results and conclusions was extracted using a pretested form and
      summarized descriptively. RESULTS: From a total of 48 potentially relevant
      reviews preselected in a screening process 39 met the inclusion criteria. 22 were
      on various pain syndromes or rheumatic diseases. Other topics addressed by more
      than one review were addiction, nausea, asthma and tinnitus. Almost unanimously
      the reviews state that acupuncture trials include too few patients. Often
      included trials are heterogeneous regarding patients, interventions and outcome
      measures, are considered to have insufficient quality and contradictory results.
      Convincing evidence is available only for postoperative nausea, for which
      acupuncture appears to be of benefit, and smoking cessation, where acupuncture is
      no more effective than sham acupuncture. CONCLUSIONS: A large number of
      systematic reviews on acupuncture exists. What is most obvious from these reviews
      is the need for (the funding of) well-designed, larger clinical trials.

PMID- 11513759
TI  - Ventilator circuit changes: "wu wei" may save time, labor, and money.

PMID- 11513760
TI  - Effects of decreasing the frequency of ventilator circuit changes to every 7 days
      on the rate of ventilator-associated pneumonia in a Beijing hospital.
AB  - INTRODUCTION: We investigated whether decreasing ventilator circuit changes from
      every 2 days to every 7 days would impact ventilator-associated pneumonia rates
      at our institution. METHODS: All mechanically ventilated patients at Peking Union
      Medical College Hospital were studied over a 21 month period. From March 1998 to
      February 1999, ventilator circuits were changed every 2 days, and from June
      through December 1999, ventilator circuits were changed every 7 days. Nosocomial
      pneumonia was identified using the criteria of the Centers for Disease Control.
      RESULTS: In the 2-day-change group, there were 2,277 ventilator-patient days and
      38 patients developed pneumonia, resulting in a pneumonia rate of 16.7 cases per
      1,000 ventilator days. The 7-day-change group accumulated 972 ventilator days and
      8 patients contracted pneumonia, resulting in a pneumonia rate of 8.2 cases per
      1,000 ventilator days. The pneumonia rate was significantly lower in the 7-day
      change group (p = 0.007). To standardize for seasonal variability, we compared
      results from the same seasonal time frames (June to December 1998 for the 2-day
      change group, and June to December 1999 for the 7-day-change group), and obtained
      similar findings: during those periods, pneumonia rates were 24.2 cases per 1,000
      ventilator days for the 2-day-change group and 8.9 cases per 1,000 ventilator
      days for the 7-day-change group (p = 0.001). CONCLUSIONS: A circuit change
      interval of 7 days had a lower risk of ventilator-associated pneumonia than a 2
      day change interval. Therefore, ventilator circuits can be safely changed every 7
      days in our setting.

PMID- 11513761
TI  - The fraction of inspired oxygen in infants receiving oxygen via nasal cannula
      often exceeds safe levels.
AB  - OBJECTIVE: Measure the fraction of inspired oxygen (F(IO(2))) in infants
      receiving supplemental oxygen via nasal cannula and identify clinical variables
      that affect F(IO(2)). METHODS: Hypopharyngeal gas samples were obtained from 20
      infants receiving oxygen via nasal cannula at flows between 0 and 4 L/min.
      F(IO(2)) was calculated using the alveolar gas equation and measurements of
      partial pressure of oxygen in the samples and the barometric pressure. RESULTS:
      F(IO(2)) increased as oxygen flow was increased. F(IO(2)) exceeded safe levels (>
      60%) in two thirds of samples when the oxygen flow was 2 L/min or higher.
      Tachypnea (respiratory rate > 40 breaths/min) was associated with lower F(IO(2)).
      CONCLUSION: Infants receiving oxygen via nasal cannula at > or = 2 L/min may be
      at risk for hyperoxic lung injury. Therefore, we recommend using the lowest
      possible oxygen flow needed to maintain normoxia in infants requiring prolonged
      oxygen therapy via nasal cannula.

PMID- 11513762
TI  - Utility of measurements of oxygen cost of breathing in predicting success or
      failure in trials of reduced mechanical ventilatory support.
AB  - OBJECTIVE: Test whether a change in oxygen consumption produced by a reduction in
      level of mechanical ventilatory support predicts failure to tolerate the
      reduction in level of support. DESIGN: Prospective study of the sensitivity and
      specificity of increased oxygen cost of breathing as a predictor of failure to
      tolerate a reduction in ventilatory support in patients undergoing weaning, using
      a protocol that incrementally reduces the level of mechanical ventilatory
      support. SETTING: University medical center. METHODS: We studied 228 trials in 30
      patients who had required mechanical ventilatory support for at least 72 hours
      and who were being weaned using a standardized protocol that provided for three
      30-minute trials of reduced mechanical ventilatory support per day, followed by
      ventilatory muscle rest. Using a metabolic monitor, we monitored oxygen
      consumption (V(O(2))) prior to and during 228 incremental reductions in level of
      mechanical ventilatory support conducted as part of a standardized weaning
      protocol. Oxygen cost of breathing was defined as the difference in V(O(2))
      (Delta V(O(2))) during the trial of reduced mechanical ventilatory support,
      compared to a 30-minute resting period immediately before the trial. A successful
      trial was defined as one that could be continued for 30 minutes without
      development of clinical signs of ventilatory failure. Changes in V(O(2)) and the
      ratio of respiratory frequency to tidal volume (f/V(T)) during a weaning trial
      were evaluated as predictors for failure of a 30-minute trial of reduced
      ventilatory support. RESULTS: A 15% increase in oxygen cost of breathing
      predicted failure in the trial, with a sensitivity of 96.6%, specificity of
      85.7%, positive predictive value of 98.5%, and negative predictive value of
      72.0%. Neither change in V(O(2)) measured early in the trial nor f/V(T) proved to
      be as successful in predicting failure to tolerate an incremental reduction in
      ventilatory support. CONCLUSION: Change in V(O(2)) following an incremental
      reduction in level of mechanical ventilatory support may be a useful predictor
      for determining which patients will rapidly fail to tolerate that level of
      reduction.

PMID- 11513764
TI  - Multidetector-row spiral computed tomography in the diagnosis of thoracic
      diseases.
AB  - Since its introduction in 1992, spiral computed tomography (CT) scanners
      constructed with a single row of detectors have revolutionized imaging of
      thoracic diseases. Current state-of-the-art models use up to 16 detectors and are
      capable of acquiring 4 contiguous slices of data with each gantry rotation;
      systems with 8 data acquisition units (and more) are currently in development.
      The principal advantages offered by these systems are increased scanning speed
      and the ability to obtain volumetric data in high resolution. These features
      enable imaging with enhanced contrast concentration, decreased contrast load,
      decreased respiratory and cardiac motion artifact, and multiplanar and 3
      dimensional reconstruction capabilities. Herein we first review the technical
      aspects of multidetector spiral CT scanning. The arrangement and various
      combinations of the detector rows are discussed. Key scanning variables,
      including collimation (slice thickness), pitch (the rate of table travel per
      gantry rotation divided by the beam collimation), and gantry speed, are briefly
      addressed in the context of their interrelationships. Comparison is made with
      single-detector-row systems to emphasize the superior scanning speed and
      resolution. We then discuss the various clinical applications of multidetector
      spiral CT, including CT pulmonary angiography, CT aortography, virtual
      bronchoscopy, and multiplanar and 3-dimensional reconstructions.

PMID- 11513765
TI  - Magnetic resonance imaging of the chest.
AB  - Thoracic magnetic resonance imaging (MRI) has recently undergone important
      advances, and newer applications could expand the role of thoracic MRI. Existing
      and developing MRI techniques are described and compared to other imaging
      techniques with regard to imaging various thoracic regions, structures, and
      diseases. After an initial discussion of MRI techniques, the role of thoracic MRI
      in evaluation of the thoracic arteries and veins is described. The next section
      focuses on specific anatomic regions; namely, the lung, mediastinum, pleural
      space, thoracic inlet, and diaphragm. The final section reviews some novel
      techniques that may improve our ability to visualize the pulmonary parenchyma and
      mediastinum.

PMID- 11513766
TI  - Thoracic sonography.
AB  - Sonography has inherent limitations for thoracic imaging because sound waves are
      reflected by bone and air space (such as in lung parenchyma). However, sonography
      is less expensive and more convenient than computed tomography (CT) or magnetic
      resonance imaging (MRI); it provides immediate information with real-time
      imaging; and it can provide information not available from a standard radiograph.
      This review describes the utility and limitations of sonography and compares
      sonography to radiography, CT, and MRI with regard to diagnosing pleural,
      pulmonary, and aortic diseases, including pneumothorax, pleural effusions and
      masses, hemothorax, empyema, consolidated lung, pneumonia, pulmonary abscess,
      pulmonary embolism, mediastinal masses, aortic dissection, aortic intramural
      hematoma, and penetrating aortic ulcers.

PMID- 11513767
TI  - Single-photon emission tomography imaging of the chest.
AB  - We review single-photon emission computed tomography (SPECT) of the chest for
      practical applications that may be used by pulmonary disease specialists. First,
      we cover SPECT uses in pulmonary thromboembolic disease. Second, SPECT's
      applications in quantitative evaluation of the lung are reviewed, with special
      emphasis on lung volume reduction surgery. Finally, we consider the use of SPECT
      to characterize somatostatin receptors in lung masses. The role of SPECT will
      always be compared to the ever-advancing place of positron emission tomography
      chest imaging for patients with pulmonary disease. We believe that SPECT will
      continue to help pulmonary specialists take care of their patients in the years
      to come.

PMID- 11513770
TI  - The challenge of objective assessment of surgical skill.

PMID- 11513771
TI  - Cytokine modifications after tension-free hernioplasty or open conventional
      inguinal hernia repair.
AB  - BACKGROUND: The purpose of this study was to evaluate the involvement of
      proinflammatory cytokines (interferon-gamma [INF-gamma], interleukin [IL]-6) and
      anti-inflammatory cytokines (IL-4, IL-l0, IL-13) in patients undergoing
      Lichtenstein tension-free hernioplasty (LH) using polypropylene prosthetic
      materials or conventional Bassini hernia (BH) repair. METHODS: Thirty-five male
      patients (age range 25 to 60 years) with unilateral inguinal hernia without
      complications or recurrence were included in this study. Randomly, patients
      underwent conventional operation and had their inguinal hernia repair performed
      with polypropylene mesh. Peripheral venous blood samples were collected 24 hours
      prior to surgery and then 6, 24, 48, and 168 hours postoperatively. Fifteen
      healthy controls were included. RESULTS: We present evidence that LH patients
      showed both an increased serum level of Thelper 1 (Th1)-like cytokines (IFN
      gamma) and an increase in Thelper 2 (Th2)-like cytokines (IL-6 and IL-l0),
      associated with a slight reduction of peripheral blood mononuclear cells (PBMC)
      producing IL-6 and a normal level of PBMC producing IFN-gamma, IL-l0, IL-13, and
      IL-4. Whereas BH patients showed in part an amplification of Th2-like cells,
      characterized by the sustained serum production of IL-6 and IL-l0, associated
      with an increase in IL-l0 secreted by in vitro stimulated PMBC. CONCLUSIONS: Our
      data show that LH is associated with a higher production of inflammatory
      cytokines (IFN-gamma and IL-6) compared with BH, likely induced by the presence
      of the polypropylene prostheses.

PMID- 11513772
TI  - Calcium channel antagonist verapamil inhibits neointimal formation and enhances
      apoptosis in a vascular graft model.
AB  - BACKGROUND: The potential of the calcium channel antagonist verapamil to cause
      apoptosis (programmed cell death) is of considerable importance in arterial
      injury where the loss of smooth muscle cells may contribute to a reduction in
      intimal hyperplasia development. The aim of this study was to determine whether
      verapamil induces vascular cell apoptosis after carotid artery synthetic
      grafting. METHODS: Thirty-two adult-female Merino sheep received gelatin sealed
      fusiform shape-Dacron grafts into the left common carotid artery at day 0. After
      operation animals were randomly allocated to either a control group or one of
      three treatment groups (groups 2, 3, and 4). Group 1 animals (n = 9) received no
      treatment. For the treatment groups, intravenous verapamil was given at a rate of
      0.5 mg/kg per day in two divided doses. Group 2, 3, and 4 sheep were treated for
      1, 2, and 4 weeks, respectively. Animals were sacrificed at 4 weeks. Apoptosis
      was detected by terminal deoxynucleotidyl transferase-mediated dUTP-fluorescent
      labelling. Proliferating cells and their phenotype were determined by
      doublestaining with antiproliferation cellular nuclei antigen and anti-alpha
      actin or anti-HAM-56. RESULTS: There were significantly more apoptotic cells in
      the perigraft adventitia in the 4-week treatment group than in the control group
      (P <0.05). The average number of proliferating cells at 2 and 4 weeks in the
      intima were significantly less than in the control (P <0.05). The average numbers
      of macrophages inside graft matrix in the 2 and 4 weeks treatment groups were
      significantly less than for the control (P <0.05). The number of proliferating
      cells inside the graft was significantly lower at 4 weeks compared with control
      (P <0.05). There was negative correlation between intimal PCNA expression and
      perigraft apoptotic expression level (P <0.05). CONCLUSION: The antihypertensive
      agent verapamil inhibits intimal hyperplasia through enhancing adventitial cell
      apoptosis and inhibiting intimal cell proliferation after vascular grafting.

PMID- 11513773
TI  - The management of neoplastic colorectal obstruction with colonic endolumenal
      stenting devices.
AB  - BACKGROUND: Colonic endolumenal stenting (CELS) to treat obstructing colorectal
      neoplasms was first described in 1991. The aim of this study was to review the
      published world literature and make recommendations for its use in current
      clinical practice. METHODS: Suitable English language reports were identified
      using a Medline search. RESULTS: CELS can been successfully accomplished in 64%
      to 100% of obstructing malignant colonic lesions. Distal lesions are more common
      and theoretically more easy to stent although lesions within the ascending colon
      have been successfully managed. Minor complications include transient anorectal
      pain and rectal bleeding, however, significant complications of stent dislocation
      and colonic perforation are also well recognized. CONCLUSION: CELS can aid the
      palliative management of malignant colorectal obstruction. Its role in relieving
      obstruction prior to resection remains to be defined. Increasing experience has
      allowed the safe placement of stents and relief of obstruction of virtually any
      lesion throughout the large bowel.

PMID- 11513774
TI  - Predictive factors for long-term survival in patients with intrahepatic
      cholangiocarcinoma.
AB  - BACKGROUND: In order to elucidate the predictive factors for long-term survival
      in patients with intrahepatic cholangiocarcinoma (ICC), we evaluated 7 patients
      who survived for more than 5 years (5-year survivors). METHODS: We examined the
      clinicopathologic and biologic factors of the 5-year survivors, and these
      findings were then compared with those in 20 patients who died within 5 years
      after surgery (control group). RESULTS: In the 5-year survivors, the gross
      appearance of the tumors included a mass-forming (MF) type in 5 cases, an
      intraductal growth (IG) type in 1, and another type (microcarcinoma with
      hepatolithiasis) in 1. No case demonstrated a periductal infiltrating (PI) type.
      Except for 1 case with an IG type tumor, no lymph node metastasis was seen in any
      patients. All of the 5-year survivors were classified from stage I to III, and
      all also underwent a curative resection. The clinicopathologic factors
      demonstrating significant differences between the 5-year survivors and the
      control group included the gross type of the tumor, lymph node involvement, the
      surgical margin, curability, and pTNM stage. CONCLUSION: The predictive factors
      for long-term survival in patients with ICC are thus suggested to include not
      only tumor staging and curability, but also lymph node metastasis and the gross
      type of the tumors.

PMID- 11513775
TI  - Effects of diphenhydramine HCl and methylprednisolone in the prevention of
      abdominal adhesions.
AB  - OBJECTIVE: The purpose of this study was to determine the effects of
      diphenhydramine hydrochloride and methylprednisolone in peritoneal adhesions.
      MATERIALS AND METHODS: Forty-eight male rats were used in the study. The rats
      were anesthetized by 5 mg/kg ketamine hydrochloride. After opening the abdomen,
      10 longitudinal incisions of 2 to 3 cm in length were made on the right parietal
      peritoneum, and a 2 cm(2) peritoneal layer was excised from the left abdominal
      wall. The abdomen was closed with 3/0 silk suture. Group I was the control group,
      group II was given 10 mg/kg diphenhydramine intravenously, group III was given 20
      mg/kg methylprednisolone intravenously, and group IV was administered both of the
      drugs in the above doses. A blood sample of 2 mL was taken from the rats on the
      14th day after the operation. The animals were then sacrificed. The abdomen was
      opened and abdominal adhesions were examined. A tissue sample of 1 g was taken
      from the abdominal incision line. Albumin, zinc, and hemoglobin levels and
      leucocyte counts in the blood were determined as well as hydroxyproline levels in
      the tissue. RESULTS: Numbers of adhesions were as follows: 9 in group I, 3 in
      group II, and 2 in group III. No adhesion was observed in group IV. Albumin,
      zinc, and hemoglobin levels and leucocyte counts were found to be similar in all
      groups. Hydroxyproline levels in the tissue were significantly lower in groups
      III and IV than in groups I and II (P <0.05). CONCLUSIONS: Diphenhydramine and
      methylprednisolone reduced postoperative adhesions significantly in rats. Further
      investigations are needed in order to use these drugs as antiadhesive agents in
      humans.

PMID- 11513776
TI  - Minimal invasive laparoscopic hysterectomy with ultrasonic scalpel.
AB  - BACKGROUND: The purpose of the study was to assess whether total laparoscopic
      hysterectomy with the ultrasonic scalpel offers advantages in term of
      intraoperative and postoperative outcomes over the conventional abdominal
      hysterectomy. METHODS: A case-control study to compare patients undergoing total
      laparoscopic hysterectomy and women undergoing abdominal hysterectomy for benign
      conditions was designed. Matching criteria were the menopausal status, the need
      of adnexectomy, and the uterus weight. The laparoscopic procedure was carried out
      using an ultrasonically activated scalpel and the amputated uterus was removed
      transvaginally. Every part of the operation was carried out via laparoscopy, from
      the adnexal phase to the colpotomy. Abdominal hysterectomy was performed using a
      conventional laparotomic technique. Intraoperative and postoperative
      characteristics were analyzed. RESULTS: One hundred forty-four patients were
      enrolled, of whom 48 underwent total laparoscopic hysterectomy and 98 abdominal
      hysterectomy. No difference was found between groups in terms of operating time
      or intraoperative and postoperative infectious and noninfectious complications.
      The median (range) total consumption of morphine (0 mg [0 to 16] versus 15 mg [0
      to 100], P <0.01) during the first 3 postoperative days was significantly lower
      in the laparoscopic group than in the laparotomic group. The median (range) time
      to regular diet (1[0 to 4] versus 2 [0 to 5], P <0.05) and the time to passage of
      stool (1[1 to 2] versus 2 [1 to 5], P <0.05) was shorter in the laparoscopic than
      in the laparotomic group. CONCLUSIONS: Total laparoscopic hysterectomy with the
      ultrasonic scalpel is feasible and safe, and offers not only cosmetic benefits
      but also reduces the need of analgesia and the time to return to a normal
      gastrointestinal function in comparison with the conventional abdominal
      hysterectomy.

PMID- 11513777
TI  - A risk score for conversion from laparoscopic to open cholecystectomy.
AB  - BACKGROUND: Laparoscopic cholecystectomy has become the standard operative
      procedure for cholelithiasis, but there are still some patients requiring
      conversion to open cholecystectomy mainly because of technical difficulty. Our
      aim was to develop a risk score for prediction of conversion from laparoscopic to
      open cholecystectomy. METHODS: Preoperative clinical, laboratory, and radiologic
      parameters of 1,000 patients who underwent laparoscopic cholecystectomy were
      analyzed for their effect on conversion rates. Six parameters (male sex,
      abdominal tenderness, previous upper abdominal operation, sonographically
      thickened gallbladder wall, age over 60 years, preoperative diagnosis of acute
      cholecystitis) were found to have significant effect in multivariate analysis. A
      constant and coefficients for these variables were calculated and formed the risk
      score. RESULTS: Overall 48 patients required conversion to open cholecystectomy
      (4.8%). These patients had significantly higher scores (mean 6.9 versus -7.2, P
      <0.001). Increasing scores resulted with significant increases in conversion
      rates and probabilities (P <0.001). Ideal cut-off point for this score was -3;
      conversion rate was 1.6% under -3, but 11.4% over this value (P <0.001).
      CONCLUSIONS: Conversion risk can be predicted easily by this score. Patients
      having high risk may be informed and scheduled appropriately. An experienced
      surgeon has to operate on these patients, and he or she has to make an early
      decision to convert in case of difficulty.

PMID- 11513778
TI  - Incidence of cancer of the pancreas, extrahepatic bile duct and ampulla of Vater
      in the United States, before and after the introduction of laparoscopic
      cholecystectomy.
AB  - BACKGROUND: Some epidemiologic studies have identified cholecystectomy as a risk
      factor for pancreatic and biliary cancer. METHODS: We compared the incidence of
      cancers of the pancreas, extrahepatic bile duct and ampulla of Vater before and
      after the widespread adoption of laparoscopic cholecystectomy in the United
      States in 1991, when the use of cholecystectomy increased dramatically. RESULTS:
      Compared with 1980 to 1991, there was no increase in the incidence of cancer of
      the pancreas (adjusted incidence rate ratio [IRR] 0.97, 95% confidence interval
      [CI] 0.94 to 0.99) or extrahepatic bile duct (IRR 0.80, 95% CI 0.74 to 0.87)
      during 1992 to 1996. There was a small increase in the incidence of ampullary
      cancer (IRR 1.14, 95% CI 1.03 to 1.26). CONCLUSIONS: We did not find clear
      evidence of a short-term increase in the incidence of cancers of the pancreas,
      bile duct, and ampulla of Vater, that was attributable to the increased use of
      cholecystectomy.

PMID- 11513779
TI  - Rare occurrence of metastatic colorectal cancers in livers with replicative
      hepatitis B infection.
AB  - BACKGROUND: It has been demonstrated that colorectal carcinomas rarely
      metastasize to diseased livers. However, this phenomenon has not been thoroughly
      evaluated in patients with various forms of chronic hepatitis B virus (HBV)
      infection. Therefore, the present study examined the relationship between the
      incidence of hepatic metastasis of colorectal carcinomas and chronic HBV
      infection, with emphasis on the influence of HBV viral replication and chronic
      liver damage. METHODS: We analyzed the clinicopathological data of 512 patients
      undergoing surgical treatment of colorectal carcinomas at our department from
      1992 to 1998. Among these cases, 74 had chronic HBV infection, including 28 cases
      with HBV replication and 21 with chronic liver damage. RESULTS: The incidence of
      liver metastasis in the HBV infection group (13.5%) was significantly lower than
      that of the noninfection group (27.1%, P <0.05). In addition, patients with HBV
      infection survived longer than those without infection (P = 0.018). Furthermore,
      liver metastatic rate in patients with HBV replication (3.6%) was lower than
      those without virus replication (19.6%, P <0.05). In contrast, there was no
      significant difference in liver metastasis between HBV infected patients with or
      without chronic liver damage (P >0.05). CONCLUSIONS: Chronic HBV infection with
      viral replication reduces hepatic metastasis of colorectal cancer, and thus
      prolongs the survival of patients.

PMID- 11513781
TI  - Microinvasive video-assisted thoracoscopic sympathicotomy for primary palmar
      hyperhidrosis.
AB  - BACKGROUND: Although video-assisted thoracoscopic surgery for palmar
      hyperhidrosis is now widely accepted as the approach of choice, the optimal
      technique has remained a subject of controversy. We have used 2-mm dual port
      video-assisted thoracoscopic sympathicotomy for primary palmar hyperhidrosis.
      This study evaluates the short-term results of the technique. METHODS: A
      retrospective review was carried out of 45 patients, 20 men and 25 women, with a
      mean age of 24.2 years. In the period from April 1998 to August 1999, 90
      consecutive video-assisted sympathicotomy for primary palmar hyperhidrosis either
      in isolation (n = 56) or in combination with axillary and plantar hyperhidrosis
      (n = 34) was performed. The mean follow-up period was 11.3 months. Attention was
      focused on patient's satisfaction, complications, and morbidity. RESULTS: Dry
      limbs were immediately achieved in all patients after surgery. There was no
      operative mortality and one case of transient Horner's syndrome developed. Eight
      of 20 with plantar hyperhidrosis showed simultaneous improvement. The overall
      mean satisfaction rate was 92% +/- 2% with a median 93% improvement using a
      visual linear analogue scale from 0% (poor) to 100% (excellent). Only 2 patients
      were dissatisfied with the operative results owing to compensatory hyperhidrosis,
      which occurred in 25 patients and improved in 20 patients within the follow-up
      period. CONCLUSIONS: The video-assisted thoracoscopic sympathicotomy with 2-mm
      endoscope is a speedy and safe way of controlling hyperhidrosis with excellent
      cosmetic results while minimizing complications.

PMID- 11513780
TI  - Minimizing cervical esophageal anastomotic complications by a modified technique.
AB  - BACKGROUND: The anastomotic leak and stricture formation after esophagectomy and
      cervical esophagogastric anastomosis deny patients with esophageal carcinoma the
      benefits of surgery. The present study was designed to ascertain whether a wide
      cross-sectional area at the site of anastomosis leads to lesser anastomotic
      complications. METHODS: One hundred patients with resectable carcinoma of the
      esophagus were randomly distributed into two groups of 50 each. All patients
      underwent one-stage transhiatal esophagectomy. In group A, 3 x 2 cm gastric
      crescent was excised from the anterior wall of the gastric tube before
      constructing the cervical esophagogastric anastomosis. No such intervention was
      done in group B, which acted as control. All patients were followed up for at
      least 3 months for detection of anastomotic complications. RESULTS: The incidence
      of anastomotic leak in the study group was significantly less in comparison with
      the control group (4.3% versus 20.8%; P = 0.03). Similarly, anastomotic stricture
      formation was significantly lower in the study group (8.5% versus 29.2%; P =
      0.02). CONCLUSIONS: A wide cross-sectional area achieved at the anastomotic site
      by removal of gastric crescent resulted in significantly lower anastomotic
      complications.

PMID- 11513782
TI  - Laparoscopic splenectomy for massive splenomegaly using a Lahey bag.
AB  - BACKGROUND: Although the recent development of hand-assisted laparoscopic surgery
      (HALS) has made the laparoscopic retraction of large spleens feasible, the
      laparoscopic removal of massively enlarged spleens (>1,000 g) remains a
      significant problem because these spleens do not fit into endoscopic bags.
      Consequently, in order to remove massive spleens either a large abdominal
      incision or morcellation of the spleen outside of an endoscopy bag is required.
      METHODS: Two patients, with spleens weighing 2,510 g and 1,720 g, underwent
      laparoscopic splenectomy using a hand port to ensure safe retraction. The massive
      spleen was placed into a Lahey bag that was inserted into the abdomen through the
      hand port site. While in the Lahey bag, the spleen was removed piecemeal through
      the hand port site. RESULTS: Both operations were completed laparoscopically
      without complications. The patients were discharged on postoperative day 2 and
      experienced minimal morbidity. CONCLUSIONS: The Lahey bag facilitates
      laparoscopic splenectomy for massive splenomegaly as even the most massive
      spleens will fit into a Lahey bag. A massive spleen may be removed piecemeal from
      the Lahey bag through the small hand port incision without risking a large
      abdominal incision, splenosis, or the insertion of a morcellator.

PMID- 11513783
TI  - Assessing laparoscopic manipulative skills.
AB  - BACKGROUND: The rapid emergence of laparoscopic surgery over the past decade has
      highlighted the need for teaching and assessing laparoscopic manipulative skills.
      Most analyses consist of a measurement of the time to complete a specified task
      and a subjective assessment by an observer. Objective assessments of accuracy in
      the performance of manipulative skills have been lacking. To quantify both speed
      and accuracy during laparoscopic skill performance, we have developed a skills
      assessment device (SAD) using a laparoscopic simulator platform and computer
      based skills assessment software that precisely measures an instrument's movement
      during performance of timed laparoscopic manipulations. STUDY DESIGN: The SAD
      device measures the time necessary for an operator to complete a task, and the
      movements of the working end of laparoscopic instruments in three dimensions. Ten
      nonsurgeons performed 10 repetitions of a standardized laparoscopic manipulation.
      Data were captured in real time for both hands on a personal computer. Accuracy
      was determined by calculating the sum of all distances traveled. Duration was
      measured in seconds. Results are group means. RESULTS: The time necessary to
      perform defined laparoscopic manipulative skills improved dramatically during the
      first 3 repetitions and then stabilized. However, accuracy of manipulations
      continued to improve over all 10 repetitions. CONCLUSIONS: When untrained
      subjects are learning a laparoscopic manipulative task, measurement of time alone
      fails to account for the more protracted learning curve for accuracy. Therefore,
      devices and training programs that fail to consider objective assessments of
      accuracy may overestimate laparoscopic proficiency.

PMID- 11513784
TI  - Creating the educated surgeon in the 21st century.
AB  - In this J. Roland Folse Invited Lecture in Surgical Education, given before the
      Association for Surgical Education, a resident considers two challenges for
      surgery and surgical training: the increasing importance of less invasive
      technologies, and the growing awareness of the importance of "systems" in care.
      As less invasive technologies evolve, the role of surgeons is being fundamentally
      challenged. Two alternative models of adaptation to technological change exist:
      the breast surgery model, in which surgeons restrict their role to providing open
      operative interventions, versus the neurosurgery model, in which surgeons adopt
      even noninvasive technologies in order to continue to manage diseases that might
      need open intervention. The neurosurgery model appears preferable but poses
      difficulties for the existing structure of surgical training. Evidence that
      surgical outcomes are critically dependent on entire teams of personnel, and not
      merely individual surgeons, may require changes in surgical training, as well.

PMID- 11513785
TI  - Strategic management simulations is a novel way to measure resident competencies.
AB  - BACKGROUND: The Strategic Management Simulation (SMS) has been used extensively
      to test and train higher cognitive functions in persons who occupy professional
      and leadership positions (i.e., skills like those needed by a surgeon). METHODS:
      The SMS was used to predict surgical residents' competency in decision making.
      Skills required for integrative surgical decision making including critical
      thinking, crisis management, flexibility, factual knowledge, and team building
      were assessed. Surgical residents with at least 2 years of experience
      participated. In additional, attending faculty familiar with the residents' work
      evaluated each resident with a standard comprehensive rating scale. Simulation
      performance on multiple measures was compared with faculty ratings. RESULTS: A
      number of measures obtained on simulation performance (eg, activity level,
      response speed, initiative, adequate usage of and appropriate search for relevant
      information) generated high correlations with comprehensive faculty assessment
      (eg, measures of crisis management, team interactions, flexibility of approach).
      CONCLUSION: The simulation technique is able to accurately assess performance of
      surgical residents (on a number of parameters) in a relatively brief time period.
      Simulation data were highly similar to faculty ratings that were based on at
      least 2 years of experience with the resident.

PMID- 11513786
TI  - Bronchoesophageal fistula secondary to broncholithiasis.

PMID- 11513787
TI  - How often does glove perforation occur in surgery? Comparison between single
      gloves and a double-gloving system.
AB  - BACKGROUND: In surgery, intact gloves protect the surgeon from bloodborne
      pathogens and the surgical wound from microorganisms on the skin of the surgeon.
      However, glove perforation is very common, and puncture rates as high as 61% are
      published in the literature. One objective of this study was to compare puncture
      rates between a unique double-gloving puncture indication system and single-use
      gloves, and another was to determine the extent to which glove perforations
      remain undetected during surgery. METHODS: The study material comprised all
      gloves used in surgical operations at our hospital for a period of 2 months. The
      analysis was made by the glove type in a prospective and randomized manner.
      Gloves were tested immediately after the surgical procedure using the approved
      standardized water-leak method for 2 minutes to detect any holes. The gloves used
      in this study were either a double-gloving puncture indication system or the
      standard glove used at our hospital. RESULTS: In 885 operations altogether, 2,462
      gloves were tested; 1,020 single gloves, 1,148 double-glove systems, and 294
      combination gloves were studied. The overall perforation rate was 192 out of
      2,462 gloves (7.80%), and 162 out of 885 operations (18.3%). The detection of
      perforation during surgery was 28 out of 76 (36.84%) with single gloves, 77 out
      of 89 with the double-gloving system (86.52%), and 9 out of 27 with combination
      gloves (33.33%; P <0.001). The inner glove of the double-gloving system was
      punctured in 6 out of 88 outer glove perforations (6.82%). CONCLUSIONS: In view
      of the critical importance of safety at work by having a sterile barrier between
      surgeon and patient, it is very important to use a double-gloving puncture
      indication system, at least in operations where there is a high risk of glove
      perforation.

PMID- 11513788
TI  - Minimally invasive video-assisted thyroidectomy.
AB  - BACKGROUND: In this paper we describe the results of our personal technique for
      minimally invasive video-assisted thyroidectomy (MIVAT). METHODS: Sixty-seven
      patients were selected for MIVAT. Selection criteria were nodule size less than
      30 mm, thyroid volume less than 20 mL, no thyroiditis, no previous neck surgery
      or irradiation. The procedure, totally gasless, is carried out through a 15-mm
      central incision above the sternal notch. Dissection is performed under
      endoscopic vision, using conventional and endoscopic instruments. RESULTS: We
      performed 51 lobectomies and 15 total thyroidectomies. Mean operative time was
      73.6 minutes for lobectomy and 109.6 minutes for total thyroidectomy. Conversion
      to open procedure was required twice (3%). We observed 2 cases of transient
      postoperative hypocalcemia and 1 case of transient recurrent laryngeal nerve
      palsy. The cosmetic result was considered excellent by most patients.
      CONCLUSIONS: MIVAT is safe and feasible. The indications are limited at present,
      but the results are encouraging, and we are optimistic about the future expansion
      of its applicability.

PMID- 11513791
TI  - Sampling and detection of Legionella pneumophila aerosols generated from an
      industrial cooling tower.
AB  - Cooling tower water has frequently been cited as a source of infection in
      outbreaks of Legionnaires' disease. However, there have been few reports on the
      presence of legionellae in aerosols from cooling towers. This paper describes our
      use of an impinger or a six-stage microbial impactor for detecting legionellae in
      air around a cooling tower contaminated with L. pneumophila (1.2+/-0.3x10(5)
      CFU/100 ml). Phosphate-buffered saline, Page's saline, 2% yeast extract solution
      and buffered yeast extract (BYE) broth were tested to evaluate their collection
      efficiency. These solutions were compared in laboratory experiments using an
      aerosol of L. pneumophila serogroup (SG) 1. Because BYE broth was the most
      efficient and storable collecting fluid among them, it was used for outdoor air
      sampling. In the outdoor air sampling, aerosolized L. pneumophila SG 6 was
      detected in the air around the cooling tower by the impinger (0.09 CFU/l. air).
      No legionellae were detected by the impactor with Legionella-selective agar
      plates (WYOalpha) because the plates were overgrown with fungi. Repetitive
      element PCR (rep-PCR) and arbitrarily primed PCR (AP-PCR) were employed to assess
      the epidemiological relationship among Legionella isolates from the air sample
      and the cooling tower water samples. L. pneumophila SG 6 isolated from the
      aerosols produced rep-PCR and AP-PCR fingerprints identical to those of L.
      pneumophila SG 6 strains from the cooling tower water, suggesting that the
      bacterium was aerosolized from the cooling tower.

PMID- 11513789
TI  - The effect of glucagon-like peptide 2 on intestinal permeability and bacterial
      translocation in acute necrotizing pancreatitis.
AB  - BACKGROUND: Acute pancreatitis (AP) initiates a generalized inflammatory response
      that increases intestinal permeability and promotes bacterial translocation (BT).
      Impairment of the intestinal epithelial barrier is known to promote BT. Glucagon
      like peptide 2 (GLP-2), a 33 residue peptide hormone, is a key regulator of the
      intestinal mucosa by stimulating epithelial growth. The purpose of this study was
      to determine whether GLP-2 decreases intestinal permeability and BT in AP.
      METHODS: To examine whether GLP-2 can decrease intestinal permeability and
      thereby decrease BT in acute necrotizing pancreatitis, 34 male Sprague-Dawley
      rats (200 to 300 g) were studied. AP was induced in group I and group II by
      pressure injection of 3% taurocholate and trypsin into the common biliopancreatic
      duct (1 mg/kg of body weight). The potent analog to GLP-2 called ALX-0600 was
      utilized. Group I rats received GLP-2 analog (0.1 mg/kg, SQ, BID) and group II
      rats received a similar volume of normal saline as a placebo postoperatively for
      3 days. Group III and group IV received GLP-2 analog and placebo, respectively.
      At 72 hours postoperatively, blood was drawn for culture of gram-negative
      organisms. Specimens from mesenteric lymph nodes (MLN), pancreas and peritoneum
      were harvested for culture of gram-negative bacteria. Intestinal resistance as
      defined by Ohm's law was determined using a modified Ussing chamber to measure
      transepithelial current at a fixed voltage. A point scoring system for five
      histologic features that include intestinal edema, inflammatory cellular
      infiltration, fat necrosis, parenchymal necrosis, and hemorrhage was used to
      evaluate the severity of pancreatitis. Specimens from MLN, pancreas, jejunum, and
      ileum were taken for pathology. RESULTS: All group I and group II rats had AP.
      The average transepithelial resistance in group I was 82.8 Omega/cm(2) compared
      with 55.9 Omega/cm(2) in group II (P <0.01). Gram-negative BT to MLN, pancreas,
      and peritoneum was 80%, 0%, and 0%, respectively in group I compared with 100%,
      30%, and 20% translocation in group II. CONCLUSION: GLP-2 treatment significantly
      decreases intestinal permeability in acute pancreatitis.

PMID- 11513792
TI  - A comparison of international silica (alpha-quartz) calibration standards by
      Fourier transform-infrared spectrophotometry.
AB  - Seven international silica (alpha-quartz) standards were examined for relative
      purity to the US National Institute of Standards and Technology (NIST) Standard
      Reference Material (SRM) 1878 Respirable alpha-quartz by Fourier Transform
      Infrared Spectrophotometry (FT-IR). The standards examined have been used in
      North America, the UK, Australia and Germany. The 189 samples analyzed included
      NIST-SRM 1878, Min-U-Sil 5, Ottawa Silica Sand, Sikron F-600, A9950 (AUST 1),
      DQ12-Robock, DQ12-Bergbau. Size distributions of the standards were determined by
      Coulter Counter to be broadly similar with equivalent spherical volume median
      diameter ranging between 1.2 and 3 microm. The results showed the standards to
      differ by as much as 30% in relative purity. Consequently, an internationally
      agreed upon calibration standard is urgently needed. Min-U-Sil 5 based NIST-SRM
      1878 or Sikron F-600 are the two most likely candidates. Any agreed standard must
      have a well characterized size distribution and closely match the respirable dust
      criteria. It should also be studied by both infrared spectrophotometry and X-ray
      diffraction techniques.

PMID- 11513793
TI  - Predicting evaporation rates and times for spills of chemical mixtures.
AB  - Spreadsheet and short-cut methods have been developed for predicting evaporation
      rates and evaporation times for spills and constrained baths of chemical
      mixtures. Steady-state and time-varying predictions of evaporation rates can be
      made for six-component mixtures, including liquid-phase non-idealities as
      expressed through the UNIFAC method for activity coefficients. A group
      contribution method is also used to estimate vapor-phase diffusion coefficients,
      which makes the method completely predictive. The predictions are estimates that
      require professional judgement in their application. One application that the
      evaporation time calculations suggest is a method for labeling chemical
      containers that allows one to quickly assess the time for complete evaporation of
      spills of both pure components and mixtures. The labeling would take the form of
      an evaporation time that depends on the local environment. For instance,
      evaporation time depends on indoor or outdoor conditions and the amount of each
      chemical among other parameters. This labeling would provide rapid information
      and an opportunity to premeditate a response before a spill occurs.

PMID- 11513794
TI  - A proposal for harmonising laboratory performance assessment criteria in national
      asbestos fibre counting schemes.
AB  - Four European national asbestos fibre counting proficiency testing schemes have
      been studied in order to compare their criteria for the assessment of laboratory
      performance. Performance assessment is based on each laboratory's results after
      counting a certain number of samples. Two methods are currently being applied. To
      be classified 'satisfactory' laboratories must obtain at least 75% of normalised
      counts lying within defined performance limits (in three schemes), or the median
      and coefficient of variation of normalised counts must be within performance
      limits (in the fourth scheme). Differences in the numbers of test samples mean
      that the schemes are operating with different selectivity in assessing their
      laboratories' performances. Differences in the percentage of laboratory results
      falling within performance limits indicate that the schemes do not operate the
      same confidence probability in correctly assessing individual counts. It means
      that some schemes may be more lenient than others. This paper discusses two
      proposals to move towards harmonisation of the asbestos fibre counting
      proficiency testing schemes: (i) standardisation of the number of samples used
      for laboratory assessment and (ii) changes to the criteria to establish the
      limits of satisfactory performance.

PMID- 11513795
TI  - Exposure assessment to airborne endotoxin, dust, ammonia, hydrogen sulfide and
      carbon dioxide in open style swine houses.
AB  - Information is limited for the exposure levels of airborne hazardous substances
      in swine feed buildings that are not completely enclosed. Open-style breeding,
      growing and finishing swine houses in six farms in subtropical Taiwan were
      studied for the airborne concentrations of endotoxin, dust, ammonia, hydrogen
      sulfide and carbon dioxide. The air in the farrowing and nursery stalls as
      partially enclosed was also simultaneously evaluated. Three selected gases and
      airborne dusts were quantified respectively by using Drager diffusion tubes and a
      filter-weighing method. Endotoxin was analyzed by the Limulus amoebocyte lysate
      assay. Average concentration of airborne total endotoxin among piggeries was
      between 36.8 and 298 EU/m(3), while that for respirable endotoxin was 14.1-129
      EU/m(3). Mean concentration of total dust was between 0.15 and 0.34 mg/m(3), with
      average level of respirable dust of 0.14 mg/m(3). The respective concentrations
      of NH3, CO2 and H2S were less than 5 ppm, 600-895 ppm and less than 0.2 ppm.
      Airborne concentrations of total dust and endotoxin in the nursery house were
      higher than in the other types of swine houses. The finishing house presented the
      highest exposure risk to NH3, CO2 and H2S. Employees working in the finishing
      stalls were also exposed to the highest airborne levels of respirable endotoxin
      and dust. On the other hand, the air of the breeding units was the least
      contaminated in terms of airborne endotoxin, dust, NH3, CO2 and H2S. The airborne
      concentrations of substances measured in the present study were all lower than
      most of published studies conducted in mainly enclosed swine buildings. Distinct
      characteristics, including maintaining swine houses in an open status and
      frequent spraying water inside the stalls, significantly reduce accumulation of
      gases and airborne particulates.

PMID- 11513796
TI  - Stratification of welding fumes and grinding particles in a large factory hall
      equipped with displacement ventilation.
AB  - The purpose of the study was to investigate the performance of displacement
      ventilation in a large factory hall where large components of stainless steel for
      paper, pulp and chemical industries were manufactured. The performance of
      displacement ventilation was evaluated in terms of concentration distributions of
      welding fumes and grinding particles, flow field of the supply air and
      temperature distributions. Large differences in vertical stratification patterns
      between hexavalent chromium (Cr(VI)) and other particulate contaminants were
      observed. The concentration of Cr(VI) was notably lower in the zone of occupancy
      than in the upper part of the factory hall, whereas the concentrations of total
      airborne particles and trivalent chromium (Cr(III)) were higher in the occupied
      zone than in the upper zone. The stratification of Cr(VI) had the same tendency
      as the air temperature stratification caused by the displacement flow field.

PMID- 11513797
TI  - Asbestos lung fibre concentrations in South African chrysotile mine workers.
AB  - Mesothelioma has not been found in South African chrysotile miners and millers
      despite decades of producing about 100000 tons of the mineral per year. One
      possible explanation for the scarcity or absence of the cancer may be a relative
      lack of contaminating fibrous tremolite, an amphibole that variably occurs with
      chrysotile ores. The fibre content in the lungs of nine former chrysotile mine
      workers was ascertained by transmission electron microscopy. Despite fairly long
      service in most cases (median 9.5 yr; range 32-4 yr) the concentrations of
      chrysotile fibres were relatively low: only two cases exceeded 1.14 million
      fibres/g dried lung. Tremolite fibre levels were even lower: less than 1 million
      fibres/g dried lung in all but one case. Tremolite fibre concentrations exceeded
      those of chrysotile in only two cases. These results support the contention that
      South African chrysotile is not heavily contaminated by tremolite.

PMID- 11513798
TI  - Associations between hand-wrist musculoskeletal and sensorineural complaints and
      biomechanical and vibration work constraints.
AB  - A 3-year prospective epidemiological study was conducted to investigate the
      relationship between musculoskeletal complaints (MS) and sensorineural complaints
      (SN) of the workers in the hand-wrist region. A group of 69 workers (G1) using
      vibrating tools in eight different working situations was compared to a group of
      62 workers (G2) performing heavy work without vibration and 46 workers (G3)
      performing light work without vibration. Biomechanical constraints (force,
      postures, repetitiveness and movement velocities) were analysed for each working
      situation and the vibration exposure at the eight workplaces with the 69 workers.
      MS and SN data were collected using the nordic questionnaire, modified to collect
      information about the frequency intensity and duration of complaints. The
      prevalence of complaints at the start of the study was significantly greater for
      G1 (72.5%) than for G2 (56.5%), itself greater than for G3 (30.4%). The
      prevalence of SN was about 40% for G1 and 2.5 times smaller in the two other
      groups. During the two years follow-up, new cases of 'serious' MS and SN
      developed. The annual incidence was respectively 8.3 and 5.4% on average. The
      incidence of MS was slightly but not statistically significantly greater for G1,
      while the incidence of SN was statistically higher (P<0.01) for G1 (10.9%) than
      for the two other groups (4.1 and 2.1%). Forces and angular repetitiveness were
      the only biomechanical factors significantly greater for G1. The vibration
      exposure duration of the G1 workers varied, in average, from 10 to 70% of the
      work time and the weighted personal exposure amplitude (A(EPw)) varied from 0.5
      to 25.4 ms(-2). The probabilities of complaints at the beginning of the study
      (cross-sectional study) were estimated using multiple logistic regression models.
      The prevalence odds ratio (POR) for MS was equal to 4 for G1 compared to G2 and
      equal to 9 compared to G3. Force and vibration exposure were the main constraint
      parameters associated with this likelihood. As far as the SN are concerned, G2
      and G3 were not statistically different, but the POR for the G1 workers was 4.5
      compared to both groups. The most significant constraint factor was the weighted
      personal exposure acceleration. The same procedure was used to estimate the
      likelihood of development of 'serious' complaints (longitudinal study). The three
      groups did not appear significantly different concerning the 'serious' MS, while
      the incidence odds ratio (IOR) of 'serious' SN was very high (28.5) and
      significantly greater for G1 than for the two other groups. The likelihood of
      development of 'serious' SN increased with A(EPw). According to this prediction
      model, the risk of 'serious' SN would be about 6% at the proposed European
      'action' value (2.5 ms(-2)) and about 10% at the 'limit' value (5 ms(-2)).

PMID- 11513799
TI  - Recognition errors in the quantification of micro-organisms by fluorescence
      microscopy.
AB  - OBJECTIVES: An interlaboratory comparison of fluorescence microscopic counting of
      micro-organisms was carried out to assess counting errors in the measurement of
      micro-organisms in bioaerosols generated during handling of municipal waste.
      METHODS: Series of 27 replicate samples were collected in the work environment
      with a modified field exposure chamber. The preparation methods of three
      Scandinavian laboratories were compared. Four microscopists from these
      laboratories performed the counts which were also compared. Duplicate counting of
      identical microscopic fields allowed the assessment of recognition errors.
      RESULTS: The field exposure chamber collected replicate samples with a relative
      standard deviation of 5% when particles < or = 15 microm aerodynamic diameter
      were collected. Storage time of 40-200 days had no significant influence on the
      total micro-organism count. Differences between preparation methods were from 2
      to 35% for bacteria, and from 15 to 35% for fungal spores when samples were
      analysed in Oslo; the results for fungal spore counts were significantly
      different (P < 0.01). These differences were not confirmed when samples were
      analysed in Umea, Copenhagen and Oslo using those laboratories methods. These
      results can be explained by less efficient redispersion of aggregates when the
      Umea and Copenhagen methods were recreated in Oslo yielding a greater number of
      innumerable aggregates. Differences between microscopists were minor for fungal
      spores (2-12%) but substantial for bacteria (4-53%). A major source of error was
      the recognition of bacteria which had a relative standard deviation (rsd) of 37%
      although a lower size limit of 0.75 microm was adopted for counting of bacteria.
      Fungal spores were recognised with much better precision (rsd 9%). CONCLUSIONS:
      Recognition errors of bacteria may be substantial and more specific fluorochromes
      are needed for fluorescence microscopic counting of micro-organisms.

PMID- 11513800
TI  - Programmable fusogenic vesicles for intracellular delivery of antisense
      oligodeoxynucleotides: enhanced cellular uptake and biological effects.
AB  - Programmable fusogenic vesicles (PFV) are liposomes composed of non-bilayer lipid
      components stabilized by the inclusion of an exchangeable poly(ethylene glycol)
      (PEG)-lipid conjugate. Vesicle destabilization by loss of the PEG-lipid results
      in recovery of the inherent fusogenic character. As a result, PFV can be designed
      to display a long circulation lifetime after i.v. administration, high
      accumulation at disease sites and full bioavailability of an encapsulated
      compound. In the present study, we investigated the potential application of PFV
      as carriers for intracellular delivery of antisense oligodeoxynucleotides (ODN).
      Antisense phosphorothioate ODN were encapsulated into PFV containing
      dioleoylphosphatidylethanolamine, cholesterol, dioleyldimethylammonium chloride
      and PEG-ceramides with different carbon chain length (C(8), C(14) and C(20)). In
      vitro fluorescent microscopy and flow cytometry analysis demonstrated that PFV
      containing PEG-ceramide C(14) provided enhanced intracellular delivery of FITC
      labelled antisense ODN compared to PFV displaying faster or slower rates of
      destabilization (containing PEG-ceramide C(8) or C(20), respectively).
      Therapeutic efficacy of PFV-encapsulated antisense ODN against two proto
      oncogenes, c-myc and bcl-2, was examined in various cell lines. At antisense
      concentrations of 0.5 microM, no significant downregulation of c-myc mRNA levels
      was observed in HEK293, B16 and MCA207 cells. However, treatment of 518A2
      melanoma cells with PFV-encapsulated antisense targeting bcl-2 at concentrations
      of 0.5 microM and 1.0 microM resulted in reduced bcl-2 mRNA level by about 20%
      and 25% after 48 h incubation. Free antisense ODN did not affect bcl-2 mRNA
      expression at the concentrations used in this study and encapsulated control
      antisense (reverse polarity) led to a non-specific increase in mRNA levels. Our
      results suggest that PFV carriers displaying appropriate rates of destabilization
      have the potential to act as intracellular delivery vehicles and may improve the
      bioavailability and potency of antisense oligonucleotides.

PMID- 11513801
TI  - Novel putative saposin-like proteins of Entamoeba histolytica different from
      amoebapores.
AB  - Amoebapores, the pore-forming proteins of Entamoeba histolytica, have been shown
      to play a pivotal role in the pathogenicity of the protozoan parasite. They
      belong to the functionally diverse family of saposin-like proteins (SAPLIPs)
      characterized by a conserved pattern of cysteine residues and the ability to
      interact with lipids. Here, we report the identification of genomic sequences
      encoding presumably novel SAPLIPs in E. histolytica and classify them in the
      structural and functional context provided by known family members. The genes of
      altogether 15 SAPLIPs are transcribed in the axenically cultured trophozoites as
      evidenced by reverse transcriptase-polymerase chain reaction. Interestingly, a
      remarkable sequence variety with a strong resemblance to that of known,
      functionally diverse SAPLIPs is present in this archaic, unicellular organism.

PMID- 11513802
TI  - Role of endocytosis in the transfection of L929 fibroblasts by
      polyethylenimine/DNA complexes.
AB  - Polyethylenimine (PEI) is one of the most efficient nonviral vectors for gene
      therapy. The aim of this study was to investigate the role of endocytosis in the
      transfection of synchronized L929 fibroblasts by PEI/DNA complexes. This was
      performed by confocal microscopy and flow cytometry, using the endocytosis marker
      FM4-64 and PEI/DNA complexes labeled either with the DNA intercalator YOYO-1, or
      with fluorescein covalently linked to PEI. Endocytosis appeared as the major if
      not the sole mode of entry of the PEI/DNA complexes into the L929 cells. The
      complexes followed a typical fluid phase endocytosis pathway and were efficiently
      taken up in less than 10 min in endosomes that did not exceed 200 nm in diameter.
      Later, the localization of the complexes became perinuclear and fusion between
      late endosomes was shown to occur. Comparison with the intracellular trafficking
      of the same complexes in EA.hy 926 cells (W.T. Godbey, K. Wu, A.G. Mikos, Proc.
      Natl. Acad. Sci. USA 96 (1999)) revealed that endocytosis of PEI/DNA complexes is
      strongly cell-dependent. In L929 cells, escape of the complexes from the
      endosomes is a major barrier for transfection. This limited the number of
      transfected cells to a few percent, even though an internalization of PEI/DNA
      complexes was observed in most cells. In addition, the entry of the complexes
      into the nucleus apparently required a mitosis and did not involve the lipids of
      the endosome membrane. This entry seems to be a short-lived event that involves
      only a few complexes.

PMID- 11513803
TI  - Probing of the substrate binding domain of lactose permease by a proton pulse.
AB  - The lactose permease of Escherichia coli coupled proton transfer across the
      bacterial inner membrane with the uptake of beta-galactosides. In the present
      study we have used the cysteine-less C148 mutant that was selectively labeled by
      fluorescein maleimide on the C148 residue, which is an active component of the
      substrate transporting cavity. Measurements of the protonation dynamics of the
      bound pH indicator in the time resolved domain allowed us to probe the binding
      site by a free diffusing proton. The measured signal was reconstructed by numeric
      integration of differential rate equations that comply with the detailed balance
      principle and account for all proton transfer reactions taking place in the
      reaction mixture. This analysis yields the rate constants and pK values of all
      residues participating in the fast proton transfer reaction between the bulk and
      the protein's surface, revealing the exposed residues that react with free
      protons in a diffusion controlled reaction and how they transfer protons among
      themselves. The magnitudes of these rate constants were finally evaluated by
      comparison with the rate predicted by the Debye-Smoluchowski equation. The
      analysis of the kinetic and pK values indicated that the protein-fluorescein
      adduct assumes two conformation states. One is dominant above pH 7.4, while the
      other exists only below 7.1. In the high pH range, the enzyme assumes a
      constrained configuration and the rate constant of the reaction of a free
      diffusing proton with the bound dye is 10 times slower than a diffusion
      controlled reaction. In this state, the carboxylate moiety of residue E126 is in
      close proximity to the dye and exchanges a proton with it at a very fast rate.
      Below pH 7.1, the substrate binding domain is in a relaxed configuration and
      freely accessed by bulk protons, and the rate of proton exchange between the dye
      and E126 is 100,000 times slower. The relevance of these observations to the
      catalytic cycle is discussed.

PMID- 11513805
TI  - Conformational limitations of glycylsarcosine as a prototypic substrate for
      peptide transporters.
AB  - Peptide transporters are present in all species to absorb the small peptides that
      occur ubiquitously as products of proteolysis. The broad substrate specificities
      of these systems allow them to be exploited therapeutically for delivery of
      peptidomimetic drugs in microbes and man. To this end, glycylsarcosine is
      currently used as a standard substrate for assaying peptidomimetic transport by
      peptide transporters. However, in this study we find it is unsuitable as a
      general substrate, based on assays of its transport by model bacterial peptide
      transporters and computer-based conformational analysis of its structure. Of the
      two generic transporters for di- and tripeptides, exemplified by Dpp and Tpp in
      Escherichia coli, only Dpp can transport glycylsarcosine. The explanation for
      this finding came from molecular modelling, which indicated that glycylsarcosine
      can adopt only a restricted range of conformers compared with typical dipeptides,
      and that of the conformers with a trans peptide bond, the majority have the
      specific psi and phi backbone torsion angles needed for molecular recognition and
      transport by Dpp but none possessed psi and phi torsions required for recognition
      by Tpp; moreover, 38% of its conformers have cis peptide bonds that are not
      substrates for any peptide transporter. Thus, using glycylsarcosine as substrate
      in competition assays with compounds that typically form conformers recognised by
      both types of peptide transporter will underestimate their transport. These
      findings have implications for assays of oral availability of peptidomimetic
      drugs such as beta-lactams, ACE inhibitors and anti-viral compounds, for which
      glycylsarcosine is routinely used.

PMID- 11513804
TI  - Mechanism of cell transfection with plasmid/chitosan complexes.
AB  - Chitosan is useful as a non-viral vector for gene delivery. Although there are
      several reports supporting the use of chitosan for gene delivery, studies
      regarding effects on transfection and the chitosan-specific transfection
      mechanism remain insufficient. In this report, the level of expression with
      plasmid/chitosan was observed to be no less than that with plasmid/lipofectin
      complexes in SOJ cells. The transfection mechanism of plasmid/chitosan complexes
      as well as the relationship between transfection activity and cell uptake was
      analyzed by using fluorescein isothiocyanate-labeled plasmid and Texas Red
      labeled chitosan. In regard to effects on transfection, there were several
      factors to affect transfection activity and cell uptake, for example: the
      molecular mass of chitosan, stoichiometry of complex, as well as serum
      concentration and pH of transfection medium. The level of transfection with
      plasmid/chitosan complexes was found to be highest when the molecular mass of
      chitosan was 40 or 84 kDa, ratio of chitosan nitrogen to DNA phosphate (N/P
      ratio) was 5, and transfection medium contained 10% serum at pH 7.0. We also
      investigated the transfection mechanism, and found that plasmid/chitosan
      complexes most likely condense to form large aggregates (5-8 microm), which
      absorb to the cell surface. After this, plasmid/chitosan complexes are
      endocytosed, and possibly released from endosomes due to swelling of lysosomal in
      addition to swelling of plasmid/chitosan complex, causing the endosome to
      rupture. Finally, complexes were also observed to accumulate in the nucleus using
      a confocal laser scanning microscope.

PMID- 11513806
TI  - The polar headgroup of the detergent governs the accessibility to water of
      tryptophan octyl ester in host micelles.
AB  - Many attempts have been made to rationalize the use of detergents for membrane
      protein studies [J. Biol. Chem. 264 (1989) 4907]. The barrier properties of the
      detergent headgroup may be one parameter critically involved in protein
      protection. In this paper, we analyzed these properties using a model system, by
      comparing the accessibility of tryptophan octyl ester (TOE) to water-soluble
      collisional quenchers (iodide and acrylamide) in three detergent micelles. The
      detergents used differed only in the chemical nature of their polar headgroups,
      zwitterionic for dodecylphosphocholine (DPC) and nonionic for octa(ethylene
      glycol) dodecyl monoether (C(12)E(8)) and dodecylmaltoside (DM). In all cases, in
      phosphate buffer at pH 7.5, the binding of 5 microM TOE was complete in the
      presence of a slight excess of detergent micelles over TOE molecules, resulting
      in a significant blue shift and greater intensity of TOE fluorescence emission.
      The resulting quantum yield of bound TOE was between 0.08 (in DPC) and 0.12 (in
      DM) with an emission maximum (lambda(max)) of approximately 335 nm whatever the
      detergent micelle. Time-resolved fluorescence intensity decays of TOE at
      lambda(max) were heterogeneous in all micelles (3-4 lifetime populations), with
      mean lifetimes of 1.7 ns in DPC, and 2 ns in both C(12)E(8) and DM. TOE
      fluorescence quenching by iodide, in detergent micelles, yielded linear Stern
      Volmer plots characteristic of a dynamic quenching process. The accessibility of
      TOE to this ion was the greatest with C(12)E(8), followed by DPC and finally DM
      (Stern-Volmer quenching constants K(sv) of 2 to 5.5 M(-1)). In contrast, the
      accessibility of TOE to acrylamide was greatest with DPC, followed by C(12)E(8)
      and finally DM (K(sv)=2.7-7.1 M(-1)). TOE also presents less rotational mobility
      in DM than in the other two detergents, as shown from anisotropy decay
      measurements. These results, together with previous TOE quenching measurements
      with brominated detergents [Biophys. J. 77 (1999) 3071] provide reference data
      for analyzing Trp characteristics in peptide (and more indirectly protein)
      detergent complexes. The main finding of this study was that TOE was less
      accessible (to soluble quenchers) in DM than in DPC and C(12)E(8), the cohesion
      of DM headgroup region being suggested to play a role in the ability of this
      detergent to protect function and stability of solubilized membrane proteins.

PMID- 11513807
TI  - Transduction to self-assembly of molecular geometry and local interactions in
      mixtures of ceramides and ganglioside GM1.
AB  - In mixed monolayers with ganglioside GM1, ceramide induces a non-ideal increase
      of the monolayer collapse pressure, a reduction of the mean molecular area and a
      decrease of the surface potential per molecule at all surface pressures. The
      critical packing parameter and van der Waals interaction energy calculated from
      monolayer data predict the transduction of changes from the molecular to the
      supramolecular level, such as formation of bilayers and possible subsequent
      facilitation of non-bilayer structures as the ceramide concentration increases,
      along with a greater thermal stability of the lipid structures. In agreement with
      the expectations from monolayer data, calorimetry, dynamic light scattering and
      electron microscopy data reveal the actual presence of phases with high phase
      transition temperatures; at about 5 mol% ceramide in the mixture, the aggregates
      change their topology from micelles to multilamellar vesicles of increasing size
      and finally to long, thin tubules as the amount of ceramide in the system
      increases.

PMID- 11513808
TI  - Phase behavior and glass transition of 1,2-dioleoylphosphatidylethanolamine
      (DOPE) dehydrated in the presence of sucrose.
AB  - The effect of sucrose on the phase behavior of 1,2
      dioleoylphosphatidylethanolamine (DOPE) as a function of hydration was studied
      using differential scanning calorimetry and X-ray diffraction. DOPE/sucrose/water
      dispersions were dehydrated at osmotic pressures (Pi) ranging from 2 to 300 MPa
      at 30 degrees C and 0 degrees C. The hexagonal II-to-lamellar gel (H(II)-
      >L(beta)) thermotropic phase transition was observed during cooling in mixtures
      dehydrated at Pi<or=35 MPa. After dehydration at Pi>or=57 MPa, the H(II)-
      >L(beta) thermotropic phase transition was precluded when sucrose entered the
      rigid glassy state while the lipid was in the H(II) phase. Sucrose also hindered
      the H(II)-to-lamellar crystalline (L(c)), and H(II)-to-inverted ribbon (P(delta))
      lyotropic phase transitions, which occurred in pure DOPE. Although the L(c) phase
      was observed in dehydrated 2:1 (mole ratio) DOPE/sucrose mixtures, it did not
      form in mixtures with higher sucrose contents (1:1 and 1:2 mixtures). The impact
      of sucrose on formation of the ordered phases (i.e., the L(c), L(beta), and
      P(delta) phases) of DOPE was explained as a trapping of DOPE in a metastable
      H(II) phase due to increased viscosity of the sucrose matrix. In addition, a
      glass transition of DOPE in the H(II) phase was observed, which we believe is the
      first report of a glass transition in phospholipids.

PMID- 11513810
TI  - Interleukin-2-induced small unilamellar vesicle coalescence.
AB  - Recombinant human interleukin-2 (rhIL-2) was incorporated in liposomes for
      potential therapeutic applications using a novel process. In this process, rhIL-2
      caused the formation of large, unique multilamellar vesicles (MLVs) from small
      unilamellar vesicles (SUVs) of dimyristoylphosphatidylcholine (DMPC). Vesicle
      coalescence occurred most rapidly at 19 degrees C, between the pre- and main
      phase transition temperatures of DMPC, and showed a dependence upon pH (pH <5.5),
      ionic strength (>50 mM) and the initial size of the unilamellar vesicles (<or=25
      nm). Intermediates (partially coalesced vesicles) within the forming
      multilamellar structures were identified by freeze-fracture electron microscopy
      and their presence was corroborated by differential scanning calorimetry. Several
      distinct steps were identified in the coalescence process. In the initial step,
      rhIL-2 rapidly bound to the DMPC SUVs. This was followed by a pH-dependent
      conformational change in the protein, as evidenced by an increase in tryptophan
      fluorescence intensity. The SUVs then aggregated in large clusters that
      eventually annealed to form closed MLVs. In this process over 90% of the rhIL-2
      was bound to and incorporated within the multilamellar structures.

PMID- 11513809
TI  - Additive stimulatory effect of extracellular calcium and potassium on non
      transferrin ferric iron uptake by HeLa and K562 cells.
AB  - We studied the effects of Ca(2+) and K(+) on non-transferrin iron uptake from
      ferric citrate complex by HeLa and K562 cells. Uptake experiments in Na-HEPES
      buffer (137 mM NaCl, 4 mM KCl) showed that extracellular Ca(2+) stimulated the
      iron uptake. The rate of iron uptake in 4 mM Ca(2+) was about 3-5 times higher
      than without Ca(2+). The iron uptake in K-HEPES buffer (68 mM NaCl, 75 mM KCl)
      with a high K(+) level was transiently stimulated during the first 10 min. The
      rate of iron uptake for 0.4 mM Ca(2+) was approximately 3 times higher in K-HEPES
      buffer than in Na-HEPES buffer. The calcium channel blockers verapamil (50
      microM) and nifedipine (5 microM) had no effect on the uptake either in control
      Na-HEPES buffer or after K(+) stimulation in K-HEPES buffer. The sodium channel
      blocker lidocaine (50 microM) also had no effect on the uptake of iron in Na
      HEPES buffer as well as after K(+) stimulation. Furthermore, the iron uptake was
      not significantly affected when Na(+) in the Na-HEPES and K-HEPES buffers was
      replaced by isotonic saccharose. We conclude that extracellular calcium per se,
      and not intracellular calcium or Ca(2+) transport, stimulates ferric iron uptake
      by both HeLa and K562 cells. A high level of extracellular K(+) also stimulates
      the uptake, probably via cell membrane depolarization. Na(+) is not involved in
      these stimulations of iron uptake. The transient K(+) effect and continuous
      Ca(2+) effect seem to be additive.

PMID- 11513811
TI  - Interaction of a cationic polymer with negatively charged proteoliposomes.
AB  - Proteoliposomes were prepared by making bilayer vesicles from neutral egg yolk
      lecithin and negatively charged alpha-chymotrypsin that had been previously
      stearoylated. Interaction of these proteoliposomes with a cationic polymer, poly
      (N-ethyl-4-vinylpryidinium bromide) (PEVP) was examined. For comparison purposes,
      interaction of PEVP with egg lecithin vesicles containing an anionic
      phospholipid, cardiolipin, was also examined. Binding of PEVP to both types of
      vesicles was electrostatic in nature with the polymer manifesting a higher
      affinity to the cardiolipin relative to the enzyme. PEVP had no effect on the
      permeability of the bilayer membranes to sodium chloride. On the other hand, PEVP
      increased the transmembrane permeability of the nonionic anti-tumor drug,
      doxorubicin. The greater the negatively charged component in the membrane, the
      greater the PEVP effect. Polycation binding to the vesicles was accompanied by
      clustering of the stearoylated chymotrypsin (sCT) molecules within the membrane.
      This protein clustering is most likely responsible for the increase in the
      doxorubicin permeation. Enzymatic activity of the membrane-associated sCT
      remained unchanged upon PEVP binding. These findings seem relevant to the effects
      of polyelectrolytes on cellular membranes.

PMID- 11513812
TI  - Selective reaction of hydroxylamine with chromophore during the photocycle of
      pharaonis phoborhodopsin.
AB  - Phoborhodopsin (pR; also called sensory rhodopsin II, sRII) is a receptor of
      negative phototaxis of Halobacterium salinarum, and pharaonis phoborhodopsin
      (ppR; also pharaonis sensory rhodopsin II, psRII) is a corresponding protein of
      Natronobacterium pharaonis. These receptors contain retinal as a chromophore
      which binds to a lysine residue via Schiff base. This Schiff base can be cleaved
      with hydroxylamine to loose their color (bleaching). In dark, the bleaching rate
      of ppR was very slow whereas illumination accelerated considerably the bleaching
      rate. Addition of azide accelerated the decay of the M-intermediate while its
      formation (decay of the L-intermediate) is not affected. The bleaching rate of
      ppR under illumination was decreased by addition of azide. Essentially no
      reactivity with hydroxylamine under illumination was observed in the case of D75N
      mutant which lacks the M-intermediate in its photocycle. Moreover, we provided
      illumination by flashes to ppR in the presence of varying concentrations of azide
      to measure the bleaching rate per one flash. A good correlation was obtained
      between the rate and the mean residence time, MRT, which was calculated from
      flash photolysis data of the M-decay. These findings reveal that water-soluble
      hydroxylamine reacts selectively with the M-intermediate and its implication was
      discussed.

PMID- 11513813
TI  - Is attention-deficit/hyperactivity disorder an energy deficiency syndrome?
AB  - Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable yet
      clinically heterogeneous syndrome associated with hypocatecholamine function in
      subcortical and prefrontal cortical regions and clinical response to medications
      that enhance catecholamine function. The goal of this article is to present a
      hypothesis about the etiology of ADHD by synthesizing these findings with recent
      experiments indicating that activity-dependent neuronal energy consumption is
      regulated by cortical astrocytes. The scientific literature was searched from
      1966 to the present using MEDLINE and relevant key words. Inattention and
      impulsivity may be related to hypofunctionality of catecholamine projection
      pathways to prefrontal cortical areas, resulting in decreased neuronal energy
      availability. This may be mediated by astrocyte catecholamine receptors that
      normally regulate energy availability during neuronal activation. At least some
      forms of ADHD may be viewed as cortical, energy-deficit syndromes secondary to
      catecholamine-mediated hypofunctionality of astrocyte glucose and glycogen
      metabolism, which provides activity-dependent energy to cortical neurons. Several
      tests of this hypothesis are proposed.

PMID- 11513814
TI  - Cerebral metabolism in major depression and obsessive-compulsive disorder
      occurring separately and concurrently.
AB  - BACKGROUND: The frequent comorbidity of major depressive disorder (MDD) and
      obsessive-compulsive disorder (OCD) suggests a fundamental relationship between
      them. We sought to determine whether MDD and OCD have unique cerebral metabolic
      patterns that remain the same when they coexist as when they occur independently.
      METHODS: [18F]-fluorodeoxyglucose positron emission tomography (PET) brain scans
      were obtained on 27 subjects with OCD alone, 27 with MDD alone, 17 with
      concurrent OCD+MDD, and 17 normal control subjects, all in the untreated state.
      Regional cerebral glucose metabolism was compared between groups. RESULTS: Left
      hippocampal metabolism was significantly lower in subjects with MDD alone and in
      subjects with concurrent OCD+MDD than in control subjects or subjects with OCD
      alone. Hippocampal metabolism was negatively correlated with depression severity
      across all subjects. Thalamic metabolism was significantly elevated in OCD alone
      and in MDD alone. Subjects with concurrent OCD+MDD had significantly lower
      metabolism in thalamus, caudate, and hippocampus than subjects with OCD alone.
      CONCLUSIONS: Left hippocampal dysfunction was associated with major depressive
      episodes, regardless of primary diagnosis. Other cerebral metabolic abnormalities
      found in OCD and MDD occurring separately were not seen when the disorders
      coexisted. Depressive episodes occurring in OCD patients may be mediated by
      different basal ganglia-thalamic abnormalities than in primary MDD patients.

PMID- 11513815
TI  - Brain metabolic changes associated with symptom factor improvement in major
      depressive disorder.
AB  - BACKGROUND: Symptoms of major depressive disorder (MDD) have been linked to
      regional brain function through imaging studies of symptom provocation in normal
      control subjects and baseline studies of subjects with MDD. We examined
      associations between change in depressive symptom factors and change in regional
      brain metabolism from before to after treatment of MDD. METHODS: Thirty-nine
      outpatients with MDD underwent 18F-fluorodeoxyglucose positron emission
      tomography scanning before and after treatment with either paroxetine or
      interpersonal psychotherapy. Associations were determined between changes in
      regional brain metabolism and changes in four Hamilton Depression Rating Scale
      factors (anxiety/somatization [ANX], psychomotor retardation [PR], cognitive
      disturbance [COGN], and sleep disturbance) and two corresponding Profile of Mood
      States subscales (tension [TENS] and fatigue [FATIG]). RESULTS: Improvement in
      ANX, PR, TENS, and FATIG factors was associated with decreasing ventral frontal
      lobe metabolism. Improvement in ANX and TENS was also associated with decreasing
      ventral anterior cingulate gyrus (AC) and anterior insula activity, whereas
      improvement in PR was associated with increasing dorsal AC activity. COGN
      improvement was associated with increasing dorsolateral prefrontal cortex
      metabolism. CONCLUSIONS: Brain regions that show significant relationships with
      symptom provocation in normal control subjects have similar relationships with
      MDD symptoms as they improve with treatment.

PMID- 11513816
TI  - Evidence of white matter tract disruption in MRI hyperintensities.
AB  - BACKGROUND: Diffusion tensor imaging (DTI) of brain tissue measures the apparent
      diffusion coefficient (ADC), or isotropic diffusion, and anisotropy, or diffusion
      as influenced by tissue structure. We hypothesized that hyperintensities, when
      compared with normal tissue by DTI, would show evidence of damage through an
      increased ADC and decreased anisotropy. We also hypothesized that DTI changes in
      hyperintensities would be similar between depressed subjects and control
      subjects. METHODS: Fourteen depressed geriatric patients and nineteen control
      subjects received DTI. The ADC and aniso-tropy of normal tissue from standard
      regions were compared with hyperintensities from these regions. The Students' t
      test compared individual regions and averaged white matter results. RESULTS:
      Hyperintensities showed higher ADC and lower anisotropy than normal regions. Gray
      matter exhibited similar trends. There was no significant difference in diffusion
      characteristics of hyperintensities between subjects and control subjects.
      CONCLUSIONS: Hyperintensities damage the structure of brain tissue, and do so
      comparably in depressed subjects and control subjects.

PMID- 11513817
TI  - Clinical and neurochemical effect of acute tryptophan depletion in unaffected
      relatives of patients with bipolar affective disorder.
AB  - BACKGROUND: The lowering of mood induced by an acute tryptophan depletion (ATD)
      has been proposed as a candidate endophenotype for the vulnerability to manic
      depressive illness. This study tests this hypothesis in relatives of probands
      from well-characterized multiplex families affected with bipolar affective
      disorder (BAD). METHODS: In a double-blind, crossover design, 20 unaffected
      relatives (URs) and 19 control subjects received either a 100-g amino acid (AA)
      drink devoid of tryptophan or a placebo, respectively. Clinical and biochemical
      effects of ATD were compared between unaffected relatives of BAD probands and age
      and sex-matched control subjects. RESULTS: At 5 hours after AA drink ingestion,
      relative to the placebo, ATD resulted in 74% and 84% decreases in total plasma
      tryptophan concentrations in control subjects and relatives of patients with BAD,
      respectively. Unlike control subjects unaffected relatives experienced a lowering
      of mood during ATD but not with the placebo. Furthermore, URs tended to show
      increased impulsivity in the ATD condition. Measurements obtained before
      ingestion of the AA drink indicated that, relative to control subjects URs
      exhibited lower serotonin platelet concentrations, lower affinity, and fewer
      binding sites of the serotonin transporter for imipramine; these differences were
      unaffected by ATD. CONCLUSION: These results replicate and extend previous
      findings suggesting that URs of patients with BAD are more susceptible to low
      tryptophan availability. This finding may bear significance in the purported role
      of serotonergic mechanisms in the vulnerability to depressive syndrome and/or
      illness.

PMID- 11513818
TI  - Sustained blockade of neurokinin-1 receptors enhances serotonin
      neurotransmission.
AB  - BACKGROUND: Antagonists of neurokinin-1 (NK(1)) receptors, through which
      substance P acts, have been proposed to belong to a new class of antidepressants
      with a unique mode of action. It was postulated that they exert this putative
      therapeutic effect independently of the serotonin (5-HT) neurons. METHODS: The
      aim of the present study was to assess, using in vivo electrophysiological
      paradigms, the effects of sustained administration of the nonpeptidic NK(1)
      antagonist CP-96,345 on the firing activity of rat dorsal raphe 5-HT neurons, the
      responsiveness of pre- and postsynaptic 5-HT(1A) receptors, and overall 5-HT
      neurotransmission in the hippocampus. RESULTS: Both short- and long-term
      treatments with CP-96,345 significantly increased the spontaneous firing activity
      of dorsal raphe 5-HT neurons, and this increase was associated with an
      attenuation of somatodendritic 5-HT(1A) autoreceptor responsiveness. In contrast,
      the inactive enantiomer of CP-96,345 at NK(1) receptors, CP-96,344, did not alter
      these parameters after short-term administration. Because 5-HT(1A) receptor
      activation inhibits the firing activity of dorsal hippocampus CA(3) pyramidal
      neurons, the degree of disinhibition produced by the selective 5-HT(1A) receptor
      antagonist WAY 100635 was determined to assess the net change in 5-HT
      neurotransmission. Intravenous injection of WAY 100635 did not disinhibit CA(3)
      pyramidal neuron firing in rats given saline, CP-96,345 for 2 days, or CP-96,344
      for 14 days, but produced a significant enhancement of firing in rats treated
      with CP-96,345 for 2 weeks. Therefore, only long-term treatment with CP-96,345
      enhanced the tonic activation of postsynaptic 5-HT(1A) receptors. CONCLUSIONS:
      Similar to all other major types of antidepressant treatments, these data
      indicate that substance P antagonists might alleviate anxiety and major
      depression, at least in part, by enhancing the degree of activation of some 5-HT
      receptors in the forebrain.

PMID- 11513819
TI  - Variable foraging demand rearing: sustained elevations in cisternal cerebrospinal
      fluid corticotropin-releasing factor concentrations in adult primates.
AB  - BACKGROUND: The authors previously reported elevated cerebrospinal fluid (CSF)
      corticotropin-releasing factor (CRF) concentrations in juvenile primates nursed
      by mothers undergoing experimentally imposed unpredictable foraging conditions in
      comparison to normally reared controls. The purpose of the present study was to
      determine if these changes would endure into young adulthood. METHODS: Cisternal
      CSF samples were obtained from those unpredictably reared young adult primates
      who had been previously studied as juveniles and age-matched ad libitum normally
      reared controls. Samples were assayed for CSF CRF. RESULTS: Concentrations of CSF
      CRF were significantly elevated in the unpredictably reared sample in comparison
      to the ad libitum-reared control group. A significant positive correlation was
      noted between juvenile and young adult CSF CRF values within the unpredictably
      reared cohort. CONCLUSIONS: Disturbances of maternal-infant attachment processes
      have an enduring impact on primate CRF function into young adulthood. The CRF
      elevations following unpredictable maternal foraging conditions appear traitlike
      in nature.

PMID- 11513820
TI  - Dawn simulation and bright light in the treatment of SAD: a controlled study.
AB  - BACKGROUND: Some small controlled studies have found that dawn simulation is
      effective in treating seasonal affective disorder (SAD). With a larger sample
      size and a longer duration of treatment, we compared dawn simulation with bright
      light therapy and a placebo condition in patients with SAD. METHOD: Medication
      free patients with SAD were randomly assigned to one of three conditions: bright
      light therapy (10,000 lux for 30 min, from 6:00 AM to 6:30 AM), dawn simulation
      (1.5 hour dawn signal from 4:30 AM to 6:00 AM peaking at 250 lux), and a placebo
      condition, a dim red light (1.5 hour dawn signal from 4:30 am to 6:00 AM peaking
      at 0.5 lux.) Over the subsequent 6 weeks, the subjects were blindly rated by a
      psychiatrist using the Structured Interview Guide for the Hamilton Depression
      Rating-Seasonal Affective Disorder Version (SIGH-SAD). We modeled the profiles of
      the remissions (SIGH-SAD < or = 8) and response (> or =50% decrease in SIGH-SAD)
      to treatment over time using Cox proportional hazards models. RESULTS: The sample
      consisted of 95 subjects who were randomized to the three conditions: bright
      light (n = 33), dawn simulation (n = 31) and placebo (n = 31). Dawn simulation
      was associated with greater remission (p <.05) and response (p <.001) rates
      compared to the placebo. Bright light did not differ significantly from the
      placebo. Dawn simulation was associated with greater remission (p <.01) and
      response (p <.001) rates compared to the bright light therapy. The mean daily
      hours of sunshine during the week before each visit were associated with a
      significant increase in likelihood of both remission (p <.001) and response (p
      <.001). CONCLUSIONS: Dawn simulation was associated with greater remission and
      response rates compared to the placebo and compared to bright light therapy. The
      hours of sunshine during the week before each assessment were associated with a
      positive clinical response.

PMID- 11513821
TI  - The effects of lithium on ex vivo cytokine production.
AB  - BACKGROUND: Studies suggest that lithium may have profound immunomodulatory
      effects in animal models as well as in humans. METHODS: In this study, whole
      blood cultures from normal control subjects were established for 5 days and the
      effects of lithium on cytokine production were investigated. Because many of
      lithium's actions have been postulated to be modulated through phosphoinositide
      (PI), protein kinase C (PKC) and cyclic adenosine monophosphate (c-AMP) signaling
      pathways, the effects of myo-inositol and prostaglandin E(2), alone or in
      combination with lithium, were also investigated. RESULTS: We found that lithium
      caused an increase in interleukin-4 and interleukin-10 levels, traditionally
      classified as T-helper lymphocyte type-2 cytokines, and a decrease in interleukin
      2 and interferon-gamma levels, traditionally classified as T-helper lymphocyte
      type-1 (TH-1) cytokines. This shift cannot be fully explained by lithium's
      actions on the PI, PKC, or c-AMP messenger systems. CONCLUSIONS: Monocytes
      exposed to lithium in the presence of a mitogen for 5 days produced a shift
      toward the production of TH-2 cytokines and away from the production of TH-1
      cytokines. The study suggests that lithium may have complex time-dependent
      effects on immune function.

PMID- 11513822
TI  - Methods for developmental studies of fear conditioning circuitry.
AB  - Psychophysiologic studies use air puff as an aversive stimulus to document
      abnormal fear conditioning in children of parents with anxiety disorders. This
      study used functional magnetic resonance imaging (fMRI) to examine changes in
      amygdala activity during air-puff conditioning among adults. Blood oxygen level
      dependent (BOLD) signal was monitored in seven adults during 16 alternating
      presentations of two different colored lights (CS+ vs. CS-), one of which was
      consistently paired with an aversive air puff. A region-of-interest analysis
      demonstrated differential change in BOLD signal in the right but not left
      amygdala across CS+ versus CS- viewing. The amygdala is engaged by pairing of a
      light with an air puff. Given that prior studies relate air-puff conditioning to
      risk for anxiety in children, these methods may provide an avenue for directly
      studying the developmental neurobiology of fear conditioning.

PMID- 11513823
TI  - Reversible dehydration of trehalose and anhydrobiosis: from solution state to an
      exotic crystal?
AB  - Physico-chemical properties of the trehalose-water system are reviewed with
      special reference to the transformations that may shed light on the mechanism of
      trehalose bio-protection. Critical analysis of solution thermodynamics is made in
      order to scrutinize trehalose properties often called 'anomalous' and to check
      the consistency of literature results. Discussion on the conversion between the
      solid state polymorphic forms is given, with a special emphasis of the
      transformations involving the newly identified anhydrous crystalline form of
      alpha,alpha-trehalose, TRE(alpha). This exotic crystal is almost 'isomorphous'
      with the dihydrate crystal structure, and possesses the unique feature of
      reversibly absorbing water to produce the dihydrate, without changing the main
      structural features. The reversible process could play a functional role in the
      well-known ability of this sugar to protect biological structures from damage
      during desiccation. The final aim of the paper is to add some new insights into
      and to reconcile previous hypotheses for the peculiar 'in vivo' action of
      trehalose.

PMID- 11513824
TI  - Synthesis and evaluation of a C-glycosyl nucleoside as an inhibitor of chitin
      synthase.
AB  - As part of our ongoing program devoted to inhibit chitin synthases, we have
      prepared a novel C-glycosyl nucleoside as metabolically stable substrate analog
      of UDP-GlcNAc. The synthetic strategy relies on the consecutive coupling of
      nucleoside and amino C-glycosyl moieties with L-tartaric acid. However, this
      compound inhibited only weakly chitin synthase I, with an IC(50) value of 20 mM.

PMID- 11513825
TI  - Synthesis of 8-C-glucosylflavones.
AB  - The syntheses of orientin, parkinsonin A, isoswertiajaponin, and parkinsonin B,
      which are 8-C-beta-D-glucopyranosyl-3',4',5,7-tetrahydroxyflavone, 5-methyl
      orientin, 7-methyl orientin, and 5,7-dimethyl orientin, respectively, are
      reported herein. The C-glucosyl phloroacetophenone derivatives were obtained via
      a regio- and stereoselective O-->C glycosyl rearrangement. Aldol condensation of
      the C-glucosyl phloroacetophenone derivatives with 3,4-bisbenzyloxybenzaldehyde
      afforded the corresponding C-glucosylchalcones. Construction of the flavone
      system by reaction with I(2)-Me(2)SO, followed by the elimination of the 5-benzyl
      protecting group in the flavone structure, yielded an orientin derivative and a
      isoswertiajaponin derivative. Methylation of the orientin derivatives with
      dimethyl sulfate afforded the parkinsonin A derivative, the isoswertiajaponin
      derivative, and the parkinsonin B derivative. Finally, hydrogenolysis of these C
      glucosylflavone derivatives led to the four 8-C-glucosylflavones. The NMR spectra
      of these C-glucosylflavones showed a duplication of signals corresponding to a
      major rotamer, along with a minor one. Based on NOESY experiments in Me(2)SO at
      ambient temperature, they adopted conformations in which the H-2"and H-4" protons
      in the glucose moiety were oriented toward the B-ring in the flavone structure.

PMID- 11513826
TI  - Synthetic explorations towards 3-deoxy-3-fluoro derivatives of D-perosamine.
AB  - Based on a literature precedent, preparation of methyl 4-azido-3,4,6-trideoxy-3
      fluoro-alpha-D-mannopyranoside (18) was attempted via fluorination of methyl 4
      azido-2-O-benzyl-4,6-dideoxy-alpha-D-altropyranoside with diethylaminosulfur
      trifluoride (DAST). Contrary to expectations, the reaction took place with
      retention of configuration at the site of the fluorination yielding methyl 4
      azido-2-O-benzyl-3,4,6-trideoxy-3-fluoro-alpha-D-altropyranoside. Treatment with
      DAST of methyl 4-azido-2-O-benzyl-4,6-dideoxy-alpha-D-allopyranoside (8), or its
      2-(p-methoxybenzyl) analog 9 resulted in fluorination with inversion of
      configuration at position 3, to give the corresponding 3-deoxy-3-fluoro
      glucopyranosides 10 and 11, respectively. Accordingly, compound 18 was prepared
      from 11, by de-p-methoxybenzylation at O-2, followed by inversion of
      configuration at C-2 in the resulting methyl 4-azido-3,4,6-trideoxy-3-fluoro
      alpha-D-glucopyranoside. The 2-O-methyl analog of 18 (19) was prepared by
      methylation of 18. Compounds 18 and 19 were converted, conventionally, into the 3
      fluoro analogs of the terminal determinants of the O-PS of Vibrio cholerae O:1,
      serotype Inaba and Ogawa, respectively.

PMID- 11513827
TI  - Cleavage of the C-C linkage between the sugar and the aglycon in C
      glycosylphloroacetophenone, and the NMR spectral characteristics of the resulting
      di-C-glycosyl compound.
AB  - The treatment of unprotected mono-C-beta-D-glucopyranosylphloroacetophenone with
      a cation-exchange resin in anhydrous acetonitrile afforded both a
      phloroacetophenone and a di-C-beta-D-glucopyranosylphloroacetophenone. Treatment
      of an unprotected mono-C-(2-deoxy-beta-D-arabino-hexopyranosyl)phloroacetophenone
      (mono-C-2-deoxy-beta-D-glucopyranosylphloroacetophenone) also afforded both the
      aglycon and di-C-(2-deoxy-beta-D-arabino-hexopyranosyl)phloroacetophenone. The
      reaction mixtures were acetylated, and the structures of the isolated products
      were determined by NMR spectroscopy. This is the first demonstration of the
      formation of a di-C-glycosyl compound during the chemical cleavage of the C-C
      linkage between the sugar and the aglycon in an aryl C-glycosyl derivative.

PMID- 11513828
TI  - Novel glycosylation of the nitroxyl radicals with peracetylated glycosyl
      fluorides using a combination of BF(3) x OEt(2) and an amine base as promoters.
AB  - Glycosylation of the nitroxyl radicals, 4-acetoxy-2,2,6,6-tetramethylpiperidin-1
      oxyl (4-acetoxy-TEMPO) and 3-carbamoyl-2,2,5,5-tetramethylpyrollin-1-oxyl (3
      carbamoyl-PROXYL) with peracetylglycosyl fluoride as the glycosyl donor, in the
      presence of boron trifluoride diethyl etherate (BF(3) x OEt(2)) and an amine base
      afforded the corresponding hydroxylamine-O-glycosides in 25-100% yields.

PMID- 11513829
TI  - Multifunctionalized alpha,beta-cyclopentenones from C-2 and C-4-ulopyranosyl
      compounds: a stereospecific rearrangement initiated by base.
AB  - Base treatment of O-benzyl protected C-2- or C-4-ulopyranosyl compounds (4 alpha,
      4 beta, and 11) by either 10% Et(3)N or 1% K(2)CO(3) in MeOH initiated a beta
      elimination to afford alpha,beta-unsaturated C-ulopyranosyl compounds (5 alpha, 5
      beta, and 12), which further rearranged in a stereocontrolled manner to
      multifuctionalized alpha,beta-cyclopentenones (6 and 14) in 70-80% yield. Both C
      alpha- and C-beta-2-ulosides (5 alpha and 5 beta) produced the same
      cyclopentenone 6, indicating that a 1,2-enolate is formed prior to the cleavage
      of the C-5--O bond. Because 6 is racemic, it was probably formed by the
      intramolecular cycloaldolization of two equally populated enantiomeric
      intermediates. When treated with 90% Et(3)N in MeOH, 5 alpha yielded almost
      exclusively 15 (isomer of 6), which was formed by a migration of the double bond
      in 5 alpha during the previously described rearrangement. Thus either 6 or 15 was
      the major product, depending on the base used.

PMID- 11513830
TI  - Infrared spectroscopic study on the properties of the anhydrous form II of
      trehalose. Implications for the functional mechanism of trehalose as a
      biostabilizer.
AB  - FTIR spectra were obtained for several different states of trehalose including
      dihydrate crystal, anhydrous form II (designated by Gil, A. M.; Belton, P. S.;
      Felix V. Spectrochim. Acta 1996, A52, 1649-1659), anhydrate crystal, dried melt,
      amorphous solid and aqueous solution. From the observation of the symmetric and
      antisymmetric stretch vibrations of the glycosidic linkage, it is found that this
      sugar assumes at least three types of backbone conformations. Among them, the
      conformation with C(2) symmetry is characterized as 'open state', which means
      that the sugar easily absorbs water molecules. The conformation of the sugars in
      anhydrous form II and in freeze-dried trehalose is shown to be in the open state.
      Next, the hygroscopic properties of the anhydrate, form II and the amorphous
      solid are compared based on their IR spectra. Interestingly, form II alone is
      converted to the original dihydrate in a week under mild environmental-like
      conditions: relative humidity of 40% and room temperature. These results suggest
      the possibility that form II plays a role in avoiding the devitrification of the
      sugar glass. Finally, we discuss the role of form II in preserving freeze-dried
      biomaterials.

PMID- 11513831
TI  - Simulation of endo-PG digest patterns and implications for the determination of
      pectin fine structure.
AB  - Novel stepwise approaches to the calculation of enzyme digest patterns are
      described and used in the validation of a computer simulation. Results obtained
      using the simulation show that, while a previously proposed model of endo-PG
      action captures some of the salient features of this enzymes behaviour, it is not
      sufficient to successfully predict experimental digest patterns from pectic
      substrates. Subsequently, it has been shown that a modified model incorporating
      existing information regarding subsite architecture and speculative site
      tolerances for esterified residues, goes someway towards improving the situation.

PMID- 11513833
TI  - Precipitated withdrawal following codeine administration is dependent on CYP
      genotype.
AB  - The role of metabolic polymorphism in the development of physical dependence to
      codeine was assessed in cytochrome P450 2D2 (CYP2D2) deficient Dark Agouti and
      CYP2D2 intact Sprague-Dawley rats by assessment of the severity of naloxone
      precipitated withdrawal after codeine and morphine administration. Plasma
      morphine concentrations after codeine were significantly higher (P<0.01) in
      Sprague-Dawley than in Dark Agouti rats with metabolic ratios of 0.71 +/- 0.27
      and 0.07 +/- 0.04, respectively. Withdrawal after codeine resulted in
      significantly greater hypothermia (3.5-4 degrees C, P<0.0001) in Sprague-Dawley
      animals compared to the other groups. Body weight loss was similar for all groups
      ranging from 6.2 +/- 0.4 to 8.2 +/- 0.6 g. When strain and treatment data were
      combined, a relationship between body temperature and plasma morphine
      concentration could be described by the inverse Hill equation (r(2)=0.76,
      EC(50)=556 +/- 121 ng/ml, n=2.9 +/- 1.5). These data indicate that dependence and
      withdrawal after codeine administration are dependent on its bioconversion to
      morphine.

PMID- 11513835
TI  - B103 neuroblastoma cells predominantly express endothelin ET(B) receptor; effects
      of extracellular Ca(2+) influx on endothelin-1-induced mitogenesis.
AB  - We sought to examine the effects of endothelin-1 on the intracellular free Ca(2+)
      concentration ([Ca(2+)](i)) and mitogenic response in the neuroblastoma cell
      line, B103 (B103 cells). The results obtained from an [125I] endothelin-1 binding
      assay demonstrated that B103 cells express the endothelin receptor. The B(max)
      and K(d) values for [125I]endothelin-1 binding were 70+/-36 fmol/mg protein and
      52+/-13 pM, respectively. Endothelin-1 failed to stimulate cAMP formation, but it
      did inhibit forskolin-induced cAMP formation. Endothelin-1 also stimulated the
      accumulation of [3H]inositol phosphates. These results indicate that the
      endothelin receptor in B103 cells couples with G(i) and G(q) but not with G(s).
      Monitoring of [Ca(2+)](i) showed that endothelin-1 evoked a transient increase in
      [Ca(2+)](i); this remained even in the absence of extracellular Ca(2+). However,
      no sustained, endothelin-1-induced increase in [Ca(2+)](i) due to extracellular
      Ca(2+) influx was detected. The endothelin B receptor-selective antagonist, 2,6
      Dimethylpiperidinecarbonyl-gamma-Methyl-Leu-N(in)-[Methoxycarbonyl]-D-Trp-D-Nle
      (BQ 788), abolished the endothelin-1-induced increase in [Ca(2+)](i), while the
      endothelin ET(A) receptor-selective antagonist, cyclo-D-Asp-Pro-D-Val-Leu-D-Trp
      (BQ 123), failed to inhibit it. These results indicate that B103 cells express
      endothelin ET(B) receptor or an endothelin ET(B)-like receptor predominantly and
      have no Ca(2+) channels activated by endothelin-1. Endothelin-1 activated mitogen
      activated protein kinase in B103 cells. However, based on the data for 3-(4,5
      dimethy-2-thiazolyl)-2,5-diphenyl tetrazolium bromide, [3H]thymidine
      incorporation, and apoptosis screening assays, endothelin-1 induces neither
      mitogenesis nor apoptosis. These results suggest that endothelin-1 has no role in
      the mitogenic response in B103 cells, and this is consistent with the notion that
      an endothelin-1-induced sustained increase in [Ca(2+)](i) plays a role in
      endothelin-1-induced cell proliferation.

PMID- 11513834
TI  - Baicalein induces a dual growth arrest by modulating multiple cell cycle
      regulatory molecules.
AB  - Baicalein, a flavonoid present in the root of Scutellaria baicalensis Georgi, has
      been reported to inhibit cell proliferation in several types of cells. In this
      study, the effect of baicalein on cell growth and the mechanism of growth
      modulation were examined in primary cultured rat heart endothelial cells. Here,
      we report that treatment with 100-microM baicalein caused an almost complete
      inhibition of cell proliferation after 5 days of incubation. Baicalein mediated
      G1 and G2 growth arrest accompanied by the down-regulation of cyclin D2, cyclin
      A, cyclin-dependent kinase 1 (Cdk1) and cyclin-dependent kinase 2 (Cdk2), and up
      regulation of p15(Ink4B), p21(CIP1/Waf1), p53 and cyclin E. Evaluation of the
      kinase activity of cyclin-Cdk complexes showed that baicalein decreased Cdk1,
      Cdk2, cyclin D2 and cyclin A expression in endothelial cells, leading to markedly
      reduced Cdk/cyclin-associated kinase activities. These results suggest that
      baicalein inhibits the proliferation of rat heart endothelial cells via G1 and G2
      arrest in association with the down-regulation of the expression and function of
      Cdk1, Cdk2, cyclin D2 and cyclin A proteins, and up-regulation of cyclin E,
      p15(Ink4B), p53 and p21(CIP1/Waf1).

PMID- 11513836
TI  - Quasi-irreversible binding of agonist to beta-adrenoceptors and formation of non
      dissociating receptor-G(s) complex in the absence of guanine nucleotides.
AB  - Here, we tested the hypothesis that receptor-G protein and agonist may form an
      irreversible complex in the absence of guanine nucleotides. We used the beta
      adrenoceptor-G(s) system of guinea pig lung parenchymal membranes as a model. Two
      groups of membranes were used in the experiments: (1) washed with nucleotide-free
      buffer in the presence of isoproterenol (isoproterenol-treated), and (2) washed
      with buffer alone or with agonist+GDP (both were treated as control). Results
      were as follows: (1) the iodopindolol binding capacity of isoproterenol-treated
      membranes was reduced by about 30%. (2) No such reduction was observed in control
      membranes. (3) Addition of GDP to the isoproterenol-treated membranes completely
      restored the pindolol binding capacity. We interpreted this result as indicating
      irreversible agonist-receptor complex is formed when the receptor interacts with
      nucleotide-free G(salpha). (4) We observed a single peak of beta(2)-adrenoceptor
      activity in the control group by size-exclusion chromatography of the solubilized
      membranes. Inclusion of isoproterenol in the washing buffer led to an additional
      (heavier) peak of beta(2)-adrenoceptor activity. This peak disappeared when GDP
      was added to the detergent extract before high-pressure liquid chromatography
      (HPLC) analysis. Western blot analysis of these HPLC fractions showed that the
      agonist-induced heavier peak contained significantly more G(salpha) protein than
      did the other fractions. We interpreted this result as indicating that a
      practically irreversible complex of receptor and G protein is formed in the
      absence of GDP. We suggest that the tightly bound (nucleotide-free) receptor-G
      protein complex also contains the agonist, and that this complex can be reversed
      only by the addition of nucleotides. The implications of these results are also
      discussed.

PMID- 11513837
TI  - Receptor-dependent formation of endogenous cannabinoids in cortical neurons.
AB  - We investigated the transduction mechanisms mediating formation of the endogenous
      cannabinoid (endocannabinoid) lipids, anandamide (arachidonylethanolamide) and 2
      arachidonylglycerol, in primary cultures of rat cortical neurons. Unstimulated
      neurons contained 0.3 +/- 0.1 pmol of anandamide and 16.5 +/- 3.3 pmol of 2
      arachidonylglycerol per mg of protein, as determined by gas chromatography/mass
      spectrometry. Ca(2+) entry into the neurons via activated glutamate N-methyl-D
      aspartate (NMDA) receptors increased 2-arachidonylglycerol levels approximately
      three times, but had no effect on anandamide levels. By contrast, anandamide
      formation was stimulated five times by simultaneous activation of NMDA and
      acetylcholine receptors. Alone, acetylcholine receptor activation had no effect
      on anandamide or 2-arachidonylglycerol levels. The formation of fatty acid
      ethanolamides that do not activate cannabinoid receptors, including
      palmitylethanolamide and oleylethanolamide, was stimulated by coactivation of
      NMDA and acetylcholine receptors. Pharmacological experiments suggest that the
      cholinergic contribution to anandamide formation was mediated by alpha7 nicotinic
      receptors (antagonized by methyllycaconitine), whereas the contribution to
      palmitylethanolamide and oleylethanolamide formation was mediated by muscarinic
      receptors (antagonized by atropine). These findings indicate that cortical
      neurons produce anandamide and 2-arachidonylglycerol in a receptor-dependent
      manner, and that brain neurons may generate different endocannabinoid lipids
      depending on their complement of neurotransmitter receptors.

PMID- 11513838
TI  - Ziprasidone: a novel antipsychotic agent with a unique human receptor binding
      profile.
AB  - Ziprasidone is a novel antipsychotic agent with a unique combination of
      pharmacological activities at human receptors. Ziprasidone has high affinity for
      human 5-HT receptors and for human dopamine D(2) receptors. Ziprasidone is a 5
      HT(1A) receptor agonist and an antagonist at 5-HT(2A), 5-HT(2C) and 5-HT(1B/1D)
      receptors. Additionally, ziprasidone inhibits neuronal uptake of 5-HT and
      norepinephrine comparable to the antidepressant imipramine. This unique
      pharmacological profile of ziprasidone may be related to its clinical
      effectiveness as a treatment for the positive, negative and affective symptoms of
      schizophrenia with a low propensity for extrapyramidal side effects, cognitive
      deficits and weight gain.

PMID- 11513839
TI  - Serotonergic effects and extracellular brain levels of eletriptan, zolmitriptan
      and sumatriptan in rat brain.
AB  - In vivo microdialysis was used to assess the central serotonergic effects and
      extracellular brain levels of the 5-HT(1B/1D) receptor agonists eletriptan,
      zolmitriptan and sumatriptan in rats after intravenous and intracerebral
      administration, while their binding affinities and functional potencies were
      determined at 5-HT(1B), 5-HT(1D) and 5-HT(1A) receptors. In vitro studies showed
      that all three triptans are high affinity, full agonists at 5-HT(1B/1D)
      receptors, but that sumatriptan is functionally less potent as a 5-HT(1B/1D)
      agonist than zolmitriptan and eletriptan. Local intracortical perfusion with the
      compounds via the dialysis probe decreased cortical 5-HT (5-hydroxytryptamine,
      serotonin) release with ED(50) values of approximately 0.1 microM for eletriptan
      and zolmitriptan and 0.5 microM for sumatriptan. At 3.2 mg/kg i.v., both
      eletriptan and zolmitriptan decreased 5-HT levels by about 35%, while sumatriptan
      had no effect, despite the fact that maximal sumatriptan concentrations in
      cortical dialysates were higher (8.8 nM at 20 min) than those of zolmitriptan
      (5.9 nM at 20 min) and eletriptan (2.6 nM at 40 min). The observation that
      eletriptan and zolmitriptan produce almost identical central serotonergic
      effects, after intracerebral as well as after systemic administration, is in
      agreement with their comparable functional 5-HT(1B/1D) receptor agonist potencies
      and their free levels in cortical dialysates after 3.2 mg/kg i.v. On the other
      hand, the lack of central serotonergic effects of 3.2 mg/kg i.v. sumatriptan is
      likely due to its weaker functional 5-HT(1B/1D) receptor agonist potency than
      eletriptan and zolmitriptan, rather than lower brain levels, consistent with
      sumatriptan's fivefold lower potency after intracerebral administration.

PMID- 11513840
TI  - Pharmacological studies of geissoschizine methyl ether, isolated from Uncaria
      sinensis Oliv., in the central nervous system.
AB  - The pharmacological properties of geissoschizine methyl ether, isolated from
      Uncaria sinensis Oliv., were analyzed in vitro and in vivo using mice central
      serotonin neurons. In the in vitro experiment, geissoschizine methyl ether
      inhibited [3H]8-hydroxy-2-(di-n-propylamino)tetralin) ([3H]8-OH-DPAT) (K(i)=0.8
      microM), [3H]mesulergine (K(i)=0.9 microM) and [3H]ketanserin (K(i)=1.4 microM),
      but had less affinity toward [3H]prazosin (K(i) > 10 microM) and [3H]spiperone
      (K(i) >15 microM) binding to mouse brain membranes. The in vivo studies showed
      that geissoschizine methyl ether dose-dependently reduced 5-hydroxy-L-tryptophan
      (I-5-HTP) plus clorgyline-induced head twitch response without inhibiting the I-5
      HTP plus clorgyline and 8-OH-DPAT-induced head weaving. On the other hand,
      geissoschizine methyl ether also decreased the rectal temperature of mice
      (hypothermic response) in a dose-dependent manner. These results suggest that
      geissoschizine methyl ether possesses mixed 5-HT(1A) receptor agonist/5-HT(2A/2C)
      receptor antagonist activities and inhibits the head twitch response by blocking
      the 5-HT(2A) receptors, and possibly, at least in part, by stimulating the 5
      HT(1A) receptors in the central nervous system.

PMID- 11513841
TI  - Roles of mast cells and sensory nerves in cutaneous vascular hyperpermeability
      and scratching behavior induced by poly-L-arginine in rats.
AB  - We investigated whether the polycation poly-L-arginine elicited cutaneous
      vascular hyperpermeability and scratching behavior and, if so, whether these
      responses involved mast cells and sensory nerves in rats. Intradermal injections
      of poly-L-arginine induced vascular hyperpermeability and scratching behavior.
      Combined treatment with chlorpheniramine and methysergide almost completely
      suppressed the poly-L-arginine (50 microg/site)-induced plasma leakage. Capsaicin
      desensitization and the tachykinin NK(1) receptor antagonist LY303870, (R)-1-[N
      (2-methoxybenzyl)acetylamino]-3-(1H-indol-3-yl)-2-[N-(2-(4-(piperidin-1
      yl)piperidin-1-yl)acetyl)amino]propane, partially inhibited the leakage. In mast
      cell-deficient rats, poly-L-arginine only minimally induced plasma leakage. On
      the other hand, capsaicin desensitization and LY303870, but not chlorpheniramine
      or methysergide, suppressed the poly-L-arginine (200 microg/site)-induced
      scratching. Moreover, poly-L-arginine elicited the scratching even in mast cell
      deficient rats. These results suggest that substance P is at least partly
      involved in both the cutaneous plasma leakage and the scratching behavior induced
      by poly-L-arginine. Moreover, mast cell-derived amines are suggested to be
      involved in the plasma extravasation but scarcely, if any, in the scratching
      behavior.

PMID- 11513842
TI  - Role of nitric oxide in histamine release from human basophils and rat peritoneal
      mast cells.
AB  - The effects of a range of nitric oxide (NO)-related compounds on histamine
      release from human basophils and rat peritoneal mast cells were studied. Basal
      and immunologic histamine releases from human basophils were not affected by
      N(omega)-nitro-L-arginine, N(omega)-nitro-L-arginine methyl ester, aminoguanidine
      or methylene blue (all inhibitors of NO production), sodium nitroprusside (an NO
      donor), L-arginine (a substrate for NO synthase) or D-arginine (the inactive
      enantiomer of L-arginine). In rat peritoneal mast cells, NO donors such as sodium
      nitroprusside, sodium nitrite and sodium nitrate, and lipopolysaccharide (an
      inducer of NO synthase) had little effect on basal histamine release, while 3
      morpholino-sydnonimine (SIN-1, an NO donor), L-arginine and D-arginine increased
      this release by up to threefold. None of the inhibitors of NO production had any
      striking effect on histamine release induced by anti-rat immunoglobulin E (IgE),
      compound 48/80, sodium fluoride, phospholipase C, 1,2-dioctanoyl-sn-glycerol or
      ionophore A23187. However, haemoglobin was found to inhibit histamine release by
      anti-rat IgE or A23187 by ca. 40%. Alone of the NO donors, low concentrations of
      L-arginine produced a mild inhibition of histamine release induced by anti-IgE,
      compound 48/80 and A23187, but not other ligands, while sodium nitroprusside dose
      dependently inhibited (by a maximum of ca. 30%) histamine release by anti-rat
      IgE, sodium fluoride or A23187. Stimulation with a variety of secretagogues or
      treatment with L-arginine, D-arginine, lipopolysaccharide, SIN-1 or sodium
      nitroprusside had no effect on NO production. Similarly, L-arginine, D-arginine
      or sodium nitroprusside did not change intracellular cGMP levels. On the basis of
      these results, it is suggested that NO does not play a significant role in the
      modulation of histamine release from human basophils or rat peritoneal mast
      cells. The effects of L-arginine, D-arginine and sodium nitroprusside may involve
      mechanisms unrelated to NO.

PMID- 11513844
TI  - Expansion of the zinc metallo-hydrolase family of the beta-lactamase fold.
AB  - Recently, the zinc metallo-hydrolase family of the beta-lactamase fold has grown
      quite rapidly, accompanied by the accumulation of sequence and structure data.
      The variety of the biological functions of the family is higher than expected. In
      addition, the members often have mosaic structures with additional domains. The
      family includes class B beta-lactamase, glyoxalase II, arylsulfatase,
      flavoprotein, cyclase/dehydrase, an mRNA 3'-processing protein, a DNA cross-link
      repair enzyme, a DNA uptake-related protein, an alkylphosphonate uptake-related
      protein, CMP-N-acetylneuraminate hydroxylase, the romA gene product,
      alkylsulfatase, and insecticide hydrolases. In this minireview, the functional
      and structural varieties of the growing protein family are described.

PMID- 11513845
TI  - Ceramide generation by two distinct pathways in tumor necrosis factor alpha
      induced cell death.
AB  - Ceramide accumulation in the cell can occur from either hydrolysis of
      sphingomyelin or by de novo synthesis. In this study, we found that blocking de
      novo ceramide synthesis significantly inhibits ceramide accumulation and
      subsequent cell death in response to tumor necrosis factor alpha. When cells were
      pre-treated with glutathione, a proposed cellular regulator of neutral
      sphingomyelinase, inhibition of ceramide accumulation at early time points was
      achieved with attenuation of cell death. Inhibition of both pathways achieved
      near-complete inhibition of ceramide accumulation and cell death indicating that
      both pathways of ceramide generation are stimulated. This illustrates the
      complexity of ceramide generation in cytokine action.

PMID- 11513846
TI  - Reconstitution of hepatitis C virus protease activities in yeast.
AB  - The hepatitis C virus (HCV) protease genes (NS2/3 and NS3) were expressed in
      yeast with their natural substrates fused to a ligand-dependent transcriptional
      activator, the retinoic acid receptor (RARbeta). RARbeta can activate
      transcription in yeast cells in response to retinoic acids. We hypothesized that
      cis-cleavage at the NS2-3 or NS3-4A junctions by the appropriate HCV proteases
      would release RARbeta, thereby activating transcription of a reporter gene. Our
      results from Western blot analyses and reporter gene activation indicate that the
      wild-type NS2/3 and NS3 enzymes are catalytically active in yeast cells, whereas
      mutations in the catalytic domain of NS2(C993V) and NS3(S1165A) lead to inactive
      enzymes. We conclude that HCV NS2/3 and NS3 protease activities can be
      reconstituted in yeast.

PMID- 11513847
TI  - Rab3a controls exocytosis in cholecystokinin-secreting cells.
AB  - The expression of rab3A and rab3D isoforms in the enteroendocrine,
      cholecystokinin-secreting, cell lines STC-1 and GLUTag is here demonstrated. In
      contrast, rab3B is undetectable in these two cell lines, and rab3C is only
      slightly expressed in GLUTag cells. Using a transient co-transfection system with
      human growth hormone as reporter protein, we show that overexpression of the
      GTPase-deficient mutant rab3AQ81L, but not rab3DQ81L, significantly decreases
      human growth hormone secretory responses to various agonists in STC-1 cells.
      These results indicate that endocrine cell lines of intestinal origin express
      rab3A and rab3D proteins, but the GTP-bound form of rab3A only acts as a negative
      modulator in the control of cholecystokinin secretion from STC-1 cells.

PMID- 11513848
TI  - The nuclear localization signal of zebrafish terra is located within the DM
      domain.
AB  - Zebrafish Terra is a member of the DM domain-containing transcription factor
      family and is involved in somitogenesis. The other known members of this family
      play a role in sex differentiation across species from Caenorhabditis elegans to
      human. Using the green fluorescence protein-Terra fusion constructs, we have
      identified the nuclear localization signal (NLS) of terra by transfecting human
      HeLa cells. The terra NLS is located between the two intertwined zinc-binding
      sites of the DNA-binding domain. However, the nuclear translocation of terra is
      independent of the structure required for DNA binding. Mutational analysis
      demonstrates that basic residues K77 and R78 within the DM domain are absolutely
      required for the translocation of Terra into the nuclei. Sequence comparison
      discloses that the NLS of Terra is also present in the other known members of the
      DM family, indicating the conservative nature of the NLS of this family during
      evolution.

PMID- 11513849
TI  - UV Raman evidence of a tyrosine in apo-human serum transferrin with a low pK(a)
      that is elevated upon binding of sulphate.
AB  - The binding of sulphate to human serum apo-transferrin has been examined by
      ultraviolet absorption and ultraviolet resonance Raman difference spectroscopies
      between pH 6.0 and 9.0. The ultraviolet absorption data reveals a negative
      feature at 245 nm that increases in magnitude with pH, with an apparent pK(a) of
      7.57, which the Raman difference data reveals to be due to tyrosine. The pK(a) of
      this tyrosine is unusually low and is measured at 7.84 by the Raman difference
      method and is elevated to greater than 9.0 upon addition of sulphate. Previous
      studies on the N-lobe imply that Tyr 188 is the tyrosine with a low pK(a) and
      also that Arg 124 is the primary binding site for the sulphate. The functional
      relevance may be that with sulphate bound, both carbonate binding and the
      deprotonation of Tyr will be disfavoured, and as a result so is iron binding.

PMID- 11513850
TI  - Sequence-specific binding property of Arabidopsis thaliana telomeric DNA binding
      protein 1 (AtTBP1).
AB  - We have identified an Arabidopsis thaliana cDNA, designated as AtTBP1, encoding a
      protein with a predicted size of 70.6 kDa that specifically binds to the plant
      telomeric repeat sequence TTTAGGG. AtTBP1 is present as a single-copy gene in
      Arabidopsis genome and is expressed ubiquitously in various organs. AtTBP1 has a
      single Myb telomeric DNA binding domain at the C-terminus and an extensive
      homology with other known telomere-binding proteins. The isolated C-terminus of
      AtTBP1 is capable of sequence-specific DNA binding to plant duplex telomeric DNA.
      These results suggest that AtTBP1 may play important roles in plant telomere
      function in vivo.

PMID- 11513851
TI  - A sensitive filter retention assay for the detection of PrP(Sc) and the screening
      of anti-prion compounds.
AB  - A hallmark of prion diseases is the accumulation of an abnormally folded prion
      protein, denoted PrP(Sc). Here we describe a new and highly sensitive method for
      the detection of PrP(Sc) in brain and other tissue samples that utilizes both
      PrP(Sc) diagnostic criteria in combination; protease resistance and aggregation.
      Upon filtration of tissue extracts derived from scrapie- or bovine spongiform
      encephalopathy-infected animals, PrP(Sc) is retained and detected on the
      membranes. Laborious steps such as SDS-PAGE and Western blotting are avoided with
      concomitant gain in sensitivity and reliability. The new procedure also proved
      useful in a screen for anti-prion compounds in a scrapie-infected cell culture
      model.

PMID- 11513852
TI  - Coenzyme Q blocks biochemical but not receptor-mediated apoptosis by increasing
      mitochondrial antioxidant protection.
AB  - Generation of free radicals is often associated with the induction and
      progression of apoptosis. Therefore, antioxidants can prove anti-apoptotic, and
      can help to elucidate specific apoptotic pathways. Here we studied whether
      coenzyme Q, present in membranes in reduced (ubiquinol) or oxidised (ubiquinone)
      forms, can affect apoptosis induced by various stimuli. Exposure of Jurkat cells
      to alpha-tocopheryl succinate (alpha-TOS), hydrogen peroxide, anti-Fas IgM or
      TRAIL led to induction of apoptosis. Cell death due to the chemical agents was
      suppressed in cells enriched with the reduced form of coenzyme Q. However,
      coenzyme Q did not block cell death induced by the immunological agents.
      Ubiquinol-10 inhibited reactive oxygen species (ROS) generation in cells exposed
      to alpha-TOS, and a mitochondrially targeted coenzyme Q analogue also blocked
      apoptosis triggered by alpha-TOS or hydrogen peroxide. Therefore, it is plausible
      that ubiquinol-10 protects cells from chemically-induced apoptosis by acting as
      an antioxidant in mitochondria. Our results also indicate that generation of free
      radicals may not be a critical step in induction of apoptosis by immunological
      agents.

PMID- 11513853
TI  - A study on the human mitochondrial RNA polymerase activity points to existence of
      a transcription factor B-like protein.
AB  - In the present work, the RNA polymerase activity of the human mitochondrial RNA
      polymerase mature protein (h-mtRPOLm) is shown, and its molecular activity
      calculated (2.1+/-0.9 min(-1)). An activity analysis of h-mtRPOLm and deleted
      versions of it has demonstrated that the entire recombinant protein is required
      for this activity. In addition, h-mtRPOLm alone or in presence of the known
      mitochondrial transcription factors (human mitochondrial transcription factor A
      and/or human mitochondrial transcription termination factor) is not able to
      initiate transcription from the specific human mitochondrial promoters pointing
      to the existence of a human mitochondrial transcription factor B-like protein.

PMID- 11513854
TI  - Evidence from time resolved studies of the P700(.+)/A1(.-) radical pair for
      photosynthetic electron transfer on both the PsaA and PsaB branches of the
      photosystem I reaction centre.
AB  - Kinetic analysis using pulsed electron paramagnetic resonance (EPR) of
      photosynthetic electron transfer in the photosystem I reaction centres of
      Synechocystis 6803, in wild-type Chlamydomonas reinhardtii, and in site directed
      mutants of the phylloquinone binding sites in C. reinhardtii, indicates that
      electron transfer from the reaction centre primary electron donor, P700, to the
      iron-sulphur centres, Fe-S(X/A/B), can occur through either the PsaA or PsaB side
      phylloquinone. At low temperature reaction centres are frozen in states which
      allow electron transfer on one side of the reaction centre only. A fraction
      always donates electrons to the PsaA side quinone, the remainder to the PsaB
      side.

PMID- 11513855
TI  - E3 ligase activity of RING finger proteins that interact with Hip-2, a human
      ubiquitin-conjugating enzyme.
AB  - To identify proteins that interact with Huntingtin-interacting protein-2 (Hip-2),
      a ubiquitin-conjugating enzyme, a yeast two-hybrid screen system was used to
      isolate five positive clones. Sequence analyses showed that, with one exception,
      all Hip-2-interacting proteins contained the RING finger motifs. The interaction
      of Hip-2 with RNF2, one of the clones, was further confirmed through in vitro and
      in vivo experiments. Mutations in the RING domain of RNF2 prevented the clone
      from binding to Hip-2, an indication that the RING domain is the binding
      determinant. RNF2 showed a ubiquitin ligase (E3) activity in the presence of Hip
      2, suggesting that a subset of RING finger proteins may have roles as E3s.

PMID- 11513856
TI  - Caspase activation in response to cytotoxic Rana catesbeiana ribonuclease in MCF
      7 cells.
AB  - Rana catesbeiana ribonuclease (RC-RNase) and onconase were proven to own anti
      tumor activity. While molecular determinants of onconase-induced cell death have
      become more explicit, the RC-RNase-induced death pathway remains presently
      unknown. Here we demonstrated that RC-RNase-induced molecular cascades in caspase
      3-deficient MCF-7 cells did not include activation of initiation caspase-8 and 
      9. Cleavage timing suggested that procaspase-2 and -6 might be processed by
      active caspase-7 in MCF-7 cells. Caspase-7 was also responsible for cleavage of
      the poly(ADP-ribose) polymerase. Furthermore, we reported that overexpression of
      Bcl-X(L) could raise the survival rates of MCF-7 cells treated with RC-RNase and
      onconase.

PMID- 11513857
TI  - The protonophore CCCP induces mitochondrial permeability transition without
      cytochrome c release in human osteosarcoma cells.
AB  - Mitochondrial permeability transition (MPT) and cytochrome c redistribution from
      mitochondria are two events associated with apoptosis. We investigated whether an
      MPT event obligatorily leads to cytochrome c release in vivo. We have previously
      shown that treatment of human osteosarcoma cells with the protonophore m
      chlorophenylhydrazone (CCCP) for 6 h induces MPT and mitochondrial swelling
      without significant cell death. Here we demonstrate that release of cytochrome c
      does not occur and the cells remain viable even after 72 h of treatment with
      CCCP. Bax is not mobilized to mitochondria under these conditions. However,
      subsequent exposure of CCCP-treated cells to etoposide or staurosporine for 48 h
      results in rapid cell death and cytochrome c release that is accompanied by Bax
      association with mitochondria, demonstrating competency of these mitochondria to
      release cytochrome c with additional triggers. Our findings suggest that MPT is
      not a sufficient condition, in itself, to effect cytochrome c release.

PMID- 11513858
TI  - Structural elements of the osteopontin SVVYGLR motif important for the
      interaction with alpha(4) integrins.
AB  - The osteopontin SVVYGLR motif binds the integrins alpha(4)beta(1) and
      alpha(9)beta(1). We show that alpha(4)beta(7) also interacts with this motif and
      that an SVVYGLR-OH peptide antagonises the alpha(4)beta(7) MAdCAM interaction.
      The important elements of this motif required to bind alpha(4)beta(1) and
      alpha(4)beta(7) were probed using a series of mutated peptides based around
      SVVYGLR. Leu167 is important for the interaction with alpha(4) integrins, as is
      the C-terminal carboxylic acid of Arg168 exposed by thrombin cleavage. The
      importance of the acidic group means that SVVYGLR has structural elements in
      common with other alpha(4) integrin-binding motifs and suggests why thrombin
      cleavage activates this motif.

PMID- 11513859
TI  - Efficient biochemical engineering of cellular sialic acids using an
      unphysiological sialic acid precursor in cells lacking UDP-N-acetylglucosamine 2
      epimerase.
AB  - Sialic acids comprise a family of terminal sugars essential for a variety of
      biological recognition systems. N-Propanoylmannosamine, an unphysiological sialic
      acid precursor, is taken up and metabolized by mammalian cells resulting in
      oligosaccharide-bound N-propanoylneuraminic acid. N-Propanoylmannosamine, applied
      to endogenously hyposialylated subclones of the myeloid leukemia HL60 and of the
      B-cell lymphoma BJA-B, both deficient in UDP-N-acetylglucosamine 2-epimerase, is
      efficiently metabolized to CMP-N-propanoylneuraminic acid resulting in up to 85%
      of glycoconjugate-associated sialic acids being unphysiological N
      propanoylneuraminic acid. Thus, UDP-N-acetylglucosamine 2-epimerase-deficient
      cell lines provide an important experimental progress in engineering cells to
      display an almost homogeneous population of defined, structurally altered sialic
      acids.

PMID- 11513860
TI  - Stimulation of nuclear sphingosine kinase activity by platelet-derived growth
      factor.
AB  - Subcellular fractionation revealed that a significant fraction of total
      sphingosine kinase, the enzyme that phosphorylates sphingosine to form the
      bioactive lipid metabolite sphingosine-1-phosphate, resides in the nuclei of
      Swiss 3T3 cells, localized to both the nuclear envelope and the nucleoplasm.
      Platelet-derived growth factor, in addition to rapidly stimulating cytosolic
      sphingosine kinase, also induced a large increase in nucleoplasm-associated
      activity after 12-24 h that correlated with progression of cells to the S-phase
      of the cell cycle and translocation of sphingosine kinase-green fluorescent
      protein fusion protein to the nuclear envelope. Our results add sphingosine
      kinase to the growing list of lipid-metabolizing enzymes associated with the
      nucleus, and suggest that sphingosine-1-phosphate may also play a role in signal
      transduction in the nucleus.

PMID- 11513861
TI  - Activation of c-Jun amino-terminal kinase is required for retinoic acid-induced
      neural differentiation of P19 embryonal carcinoma cells.
AB  - P19 embryonal carcinoma cells are known to differentiate into neurons and glia
      when treated with relatively high concentrations (>100 nM) of retinoic acid (RA).
      Concomitant with this RA-induced neural differentiation, we observed an
      activation of the c-Jun amino-terminal kinase (JNK). JNK was required for the RA
      induced neural differentiation, because dominant-negative JNK blocked the
      differentiation. Studies using protein phosphatase inhibitors and protein kinase
      inhibitors suggested that both okadaic acid-sensitive protein phosphatase(s) and
      protein kinase C participate in the RA-induced activation of JNK.

PMID- 11513862
TI  - Phospholipid membrane restructuring induced by saposin C: a topographic study
      using atomic force microscopy.
AB  - The enzymatic activity of glucosylceramidase depends on the presence of saposin C
      (Sap C) and acidic phospholipid-containing membranes. In order to delineate the
      mechanism underlying Sap C stimulation of the enzyme activity, it is important to
      understand how Sap C interacts with phospholipid membranes. We studied the
      dynamic process of Sap C interaction with planar phospholipid membranes, in real
      time, using atomic force microscopy (AFM). The phospholipid membrane underwent
      restructuring upon addition of Sap C. The topographic characteristics of the
      membrane restructuring include the appearance of patch-like new features,
      initially emerged at the edge of phospholipid membranes and extended laterally
      with time. Changes in the image contrast of the phospholipid membrane observed
      after the Sap C addition indicate that a new phase of lipid-protein structure has
      formed during membrane restructuring. The process of membrane restructuring is
      dynamic, commencing shortly after Sap C addition, and continuing throughout the
      duration of AFM imaging (about 30 min, sometimes over 1 h). This study
      demonstrated the potential of AFM real-time imaging in studying protein-membrane
      interactions.

PMID- 11513863
TI  - Flavonoid glucuronides are substrates for human liver beta-glucuronidase.
AB  - Quercetin glucuronides are the main circulating metabolites of quercetin in
      humans. We hypothesise that the potential availability of the aglycone within
      tissues depends on the substrate specificity of the deconjugating enzyme beta
      glucuronidase towards circulating flavonoid glucuronides. Human tissues (small
      intestine, liver and neutrophils) exhibited beta-glucuronidase against quercetin
      glucuronides. The various quercetin glucuronides were deconjugated at similar
      rates, but liver cell-free extracts were the most efficient and the activity was
      completely inhibited by saccharo-1,4-lactone (a beta-glucuronidase inhibitor).
      Furthermore, pure recombinant human beta-glucuronidase hydrolysed various
      flavonoid glucuronides, with a 20-fold variation in catalytic efficiency
      (k(cat)/K(m)=1.3x10(3) M(-1) s(-1) for equol-7-O-glucuronide and 26x10(3) M(-1)
      s(-1) for kaempferol-3-O-glucuronide). Similar catalytic efficiencies were
      obtained for quercetin O-glucuronides substituted at different positions. These
      results show that flavonoid glucuronides can be deconjugated by microsomal beta
      glucuronidase from various human cells.

PMID- 11513864
TI  - Modification of Arg-13 of mu-conotoxin GIIIA with piperidinyl-Arg analogs and
      their relation to the inhibition of sodium channels.
AB  - mu-Conotoxin GIIIA, a peptide toxin isolated from the marine snail Conus
      geographus, preferentially blocks skeletal muscle sodium channels in vertebrates.
      In this study, analogs of mu-conotoxin GIIIA in which essential Arg-13 was
      replaced with arginine analogs consisting of a piperidyl framework to regulate
      length and direction of the side chain were synthesized. Synthesized analogs
      exhibited similar CD and NMR spectra to that of GIIIA, suggesting a three
      dimensional structure identical to that of the native toxin. The biological
      activities of piperidyl analogs were decreased or lost despite the small change
      in the side chain of Arg-13. The investigated structure-activity relationships in
      inhibiting electrically stimulated muscle contraction suggest that the
      guanidinium group at amino acid position 13 interacts best when spaced with three
      to four carbons and placed in a vertical direction from the peptide loop. Thus,
      the position of the guanidinium group at Arg-13 of GIIIA must be located in a
      certain range for its strong interaction with the channel protein.

PMID- 11513865
TI  - Sea urchin sperm cation-selective channels directly modulated by cAMP.
AB  - Components of the sea urchin outer egg jelly layer such as speract drastically
      change second messenger levels and membrane permeability in sperm. Ion channels
      are deeply involved in the sperm-egg dialogue in sea urchin and other species.
      Yet, due to the small size of sperm, studies of ion channels and their modulation
      by second messengers in sperm are scarce. In this report we offer the first
      direct evidence that cation-selective channels upwardly regulated by cAMP operate
      in sea urchin sperm. Due to their poor selectivity among monovalent cations,
      channel activation in seawater could contribute to sperm membrane repolarization
      during the speract response.

PMID- 11513866
TI  - C-terminal propeptide of the Caldariomyces fumago chloroperoxidase: an
      intramolecular chaperone?
AB  - The Caldariomyces fumago chloroperoxidase (CPO) is synthesised as a 372-aa
      precursor which undergoes two proteolytic processing events: removal of a 21-aa N
      terminal signal peptide and of a 52-aa C-terminal propeptide. The Aspergillus
      niger expression system developed for CPO was used to get insight into the
      function of this C-terminal propeptide. A. niger transformants expressing a CPO
      protein from which the C-terminal propeptide was deleted failed in producing any
      extracellular CPO activity, although the CPO polypeptide was synthesised.
      Expression of the full-length gene in an A. niger strain lacking the KEX2-like
      protease PclA also resulted in the production of CPO cross-reactive material into
      the culture medium, but no CPO activity. Based on these results, a function of
      the C-terminal propeptide in CPO maturation is indicated.

PMID- 11513867
TI  - The anion conductance of the glutamate transporter EAAC1 depends on the direction
      of glutamate transport.
AB  - The steady-state and pre-steady-state kinetics of glutamate transport by the
      neuronal glutamate transporter EAAC1 were determined under conditions of outward
      glutamate transport and compared to those found for the inward transport mode. In
      both transport modes, the glutamate-induced current is composed of two
      components, the coupled transport current and the uncoupled anion current, and
      inhibited by a specific non-transportable inhibitor. Furthermore, the glutamate
      independent leak current is observed in both transport modes. Upon a glutamate
      concentration jump outward transport currents show a distinct transient phase
      that deactivates within 15 ms. The results demonstrate that the general
      properties of EAAC1 are symmetric, but the rates of substrate transport and anion
      flux are asymmetric with respect to the orientation of the substrate binding site
      in the membrane. Therefore, the EAAC1 anion conductance differs from normal
      ligand-gated ion channels in that it can be activated by glutamate and Na(+) from
      both sides of the membrane.

PMID- 11513868
TI  - Functional roles of conserved transmembrane prolines in the human VPAC(1)
      receptor.
AB  - The importance of three conserved transmembrane prolines of the human vasoactive
      intestinal polypeptide (VPAC)(1) receptor was examined by single alanine
      substitution. P266A, P300A and P348A reduced the expression level, but maintained
      the binding to VIP. P266A showed decreased ability to stimulate cAMP, while P300A
      and P348A displayed an increased potency in cAMP production combined with a high
      sensitivity towards GTP compared to the wild type receptor. In addition,
      substitutions of two conserved leucines located in position -2 and +1 from P348
      were investigated. L346A and L349A reduced the receptor expression, influenced
      the G protein coupling and decreased the receptor activity. These observations,
      which are the first on conserved transmembrane prolines within this family of
      receptors, indicate that these residues are important for receptor expression, G
      protein coupling and receptor activity.

PMID- 11513869
TI  - mik1(+) G1-S transcription regulates mitotic entry in fission yeast.
AB  - In the fission yeast Schizosaccharomyces pombe Mik1p, in combination with Wee1p,
      is an important inhibitor of mitosis through direct phosphorylation of Cdc2p.
      Here we present the observation that mik1(+) is transcribed during G1- and S
      phase in normally dividing cells. mik1(+) transcription is regulated by the MCB
      DSC1 system, which controls expression of other genes at the G1-S interval.
      mik1(+) is shown to be an important target of MCB-DSC1 as it is epistatic for the
      mitotic delay phenotype displayed in cdc10-C4 cells, which are mutated in a
      component of DSC1. The mitotic delay in cdc10-C4 cells is bypassed by cdc2-1w,
      suggesting that mik1(+) acts directly on cdc2(+), with no checkpoint function
      involved. Thus, mik1(+) represents a new type of MCB-DSC1 regulated gene in
      fission yeast, whose gene product is exclusively expressed during G1- and S-phase
      to prevent premature mitosis during this cell cycle stage.

PMID- 11513870
TI  - Identification of novel cellular proteins that bind to the LC8 dynein light chain
      using a pepscan technique.
AB  - Dynein is a minus end-directed microtubule motor that serves multiple cellular
      functions. We have performed a fine mapping of the 8 kDa dynein light chain (LC8)
      binding sites throughout the development of a library of consecutive synthetic
      dodecapeptides covering the amino acid sequences of the various proteins known to
      interact with this dynein member according to the yeast two hybrid system. Two
      different consensus sequences were identified: GIQVD present in nNOS, in DNA
      cytosine methyl transferase and also in GKAP, where it is present twice in the
      protein sequence. The other LC8 binding motif is KSTQT, present in Bim, dynein
      heavy chain, Kid-1, protein 4 and also in swallow. Interestingly, this KSTQT
      motif is also present in several viruses known to associate with microtubules
      during retrograde transport from the plasma membrane to the nucleus during viral
      infection.

PMID- 11513871
TI  - Zn(2+) binding to the cytoplasmic side of Paracoccus denitrificans cytochrome c
      oxidase selectively uncouples electron transfer and proton translocation.
AB  - Using a combination of stopped-flow spectrophotometric proton pumping
      measurements and time-resolved potential measurements on black lipid membranes,
      we have investigated the effect of Zn(2+) ions on the proton transfer properties
      of Paracoccus denitrificans cytochrome c oxidase. When zinc was enclosed in the
      interior of cytochrome c oxidase containing liposomes, the H/e stoichiometry was
      found to gradually decrease with increasing Zn(2+) concentration. Half-inhibition
      of proton pumping was observed at [Zn(2+)](i)=75 microM corresponding to about 5
      6 Zn(2+) ions per oxidase molecule. In addition, there was a significant increase
      in the respiratory control ratio of the proteoliposomes upon incorporation of
      Zn(2+). Time-resolved potential measurements on a black lipid membrane showed
      that the electrogenic phases slowed down in the presence of Zn(2+) correspond to
      phases that have been attributed to proton uptake from the cytoplasmic side and
      to proton pumping. We conclude that Zn(2+) ions bind close to or within the two
      proton transfer pathways of the bacterial cytochrome c oxidase.

PMID- 11513872
TI  - A transient kinetic study on the reactivity of recombinant unprocessed monomeric
      myeloperoxidase.
AB  - Spectral and kinetic features of the redox intermediates of human recombinant
      unprocessed monomeric myeloperoxidase (recMPO), purified from an engineered
      Chinese hamster ovary cell line, were studied by the multi-mixing stopped-flow
      technique. Both the ferric protein and compounds I and II showed essentially the
      same kinetic behavior as the mature dimeric protein (MPO) isolated from
      polymorphonuclear leukocytes. Firstly, hydrogen peroxide mediated both oxidation
      of ferric recMPO to compound I (1.9 x 10(7) M(-1) s(-1), pH 7 and 15 degrees C)
      and reduction of compound I to compound II (3.0 x 10(4) M(-1) s(-1), pH 7 and 15
      degrees C). With chloride, bromide, iodide and thiocyanate compound I was reduced
      back to the ferric enzyme (3.6 x 10(4) M(-1) s(-1), 1.4 x 10(6) M(-1) s(-1), 1.4
      x 10(7) M(-1) s(-1) and 1.4 x 10(7) M(-1) s(-1), respectively), whereas the
      endogenous one-electron donor ascorbate mediated transformation of compound I to
      compound II (2.3 x 10(5) M(-1) s(-1)) and of compound II back to the resting
      enzyme (5.0 x 10(3) M(-1) s(-1)). Comparing the data of this study with those
      known from the mature enzyme strongly suggests that the processing of the
      precursor enzyme (recMPO) into the mature form occurs without structural changes
      at the active site and that the subunits in the mature dimeric enzyme work
      independently.

PMID- 11513873
TI  - The anti-apoptotic protein BAG-3 is overexpressed in pancreatic cancer and
      induced by heat stress in pancreatic cancer cell lines.
AB  - Pancreatic cancer cells are usually resistant to apoptosis mediated by intrinsic
      or extrinsic factors. BAG-3 (Bis, CAIR), which was identified as a BAG-1-related
      protein, is a novel modulator of cellular anti-apoptotic activity that functions
      through its interaction with Bcl-2. In this study we analyzed BAG-3 expression in
      human pancreatic cancer tissues and cell lines. BAG-3 mRNA was expressed at
      moderate to high levels in all pancreatic cancer samples, but at low levels in
      normal pancreas tissues. In situ hybridization and immunohistochemistry analysis
      revealed that BAG-3 was present in the cancer cells within the pancreatic tumor
      mass. When BAG-3 mRNA was analyzed in other gastrointestinal cancers
      (hepatocellular carcinoma; esophageal, stomach and colon cancer), no difference
      was found from their corresponding normal controls. In pancreatic cancer cells,
      BAG-3 mRNA expression levels were strongly induced after heat stress, but not in
      response to members of the tumor necrosis factor (TNF)-alpha family (TNF-alpha,
      TRAIL, FasL). These findings indicate that in pancreatic cancer, in contrast to
      other gastrointestinal malignancies, increased levels of BAG-3 might function to
      block apoptosis. This characteristic of pancreatic cancer might contribute to its
      more aggressive growth behavior and poor responsiveness to treatment in vivo.

PMID- 11513874
TI  - Specific collagenolysis by gelatinase A, MMP-2, is determined by the hemopexin
      domain and not the fibronectin-like domain.
AB  - In view of the essential role of the hemopexin domain of the traditional
      interstitial collagenases, MMP-1, -8, -13 and MT1-MMP (MMP-14), in determining
      specific collagen cleavage we have studied the function of this domain in MMP-2,
      relative to that of the fibronectin-like domain that promotes gelatinolysis.
      Although the fibronectin-like domain promotes avid binding to collagen, our data
      demonstrate that the catalytic and hemopexin domains of MMP-2 are sufficient to
      effect the critical step in cleavage of rat type I collagen into 3/4 and 1/4
      fragments. The mechanism of MMP-2 cleavage of collagen proceeds in two phases,
      the first resembling that of the interstitial collagenases, followed by
      gelatinolysis, promoted by the fibronectin-like domain.

PMID- 11513875
TI  - Internalization-defective mutants of somatostatin receptor subtype 2 exert normal
      signaling functions in hematopoietic cells.
AB  - The regulatory peptide somatostatin (SST) acts via a family of G-protein-coupled
      receptors comprising five subtypes (SSTR1-5). G-protein-coupled receptors
      activate multiple signaling mechanisms, which variably depend on internalization
      and intracellular routing of activated receptors. We have recently demonstrated
      that hematopoietic precursors express SSTR2 and that SST is a chemoattractant for
      these cells. Herein, we characterize critical regions in SSTR2 involved in
      endocytosis and describe how ligand-induced internalization impacts on two major
      signaling functions of SSTR2 in hematopoietic cells, the activation of the Erk
      pathway and the induction of promigratory responses.

PMID- 11513876
TI  - The cysteine residue of the SoxY protein as the active site of protein-bound
      sulfur oxidation of Paracoccus pantotrophus GB17.
AB  - Four proteins of Paracoccus pantotrophus are required for hydrogen sulfide-,
      sulfur-, thiosulfate- and sulfite-dependent horse heart cytochrome c reduction.
      The lack of free intermediates suggested a protein-bound sulfur oxidation
      mechanism. The SoxY protein has a novel motif containing a cysteine residue.
      Electrospray ionization and matrix-assisted laser desorption ionization mass
      spectrometry of the SoxYZ protein revealed one mass for SoxZ and different masses
      for SoxY, indicating native SoxY (10977 Da) and SoxY with additional masses of
      +32, +80, +112 and +144 Da, suggesting addition of sulfur, sulfite, thiosulfate
      and thioperoxomonosulfate. Reduction of SoxY removed the additional masses,
      indicating a thioether or thioester bond. N-Ethylmaleimide inhibited thiosulfate
      oxidation and the kinetics suggested a turn-over-dependent mode of action. These
      data were evidence that the sulfur atom to be oxidized was covalently linked to
      the thiol moiety of the cysteine residue of SoxY and the active site of sulfur
      oxidation.

PMID- 11513877
TI  - Use of HDEL-tagged Trichoderma reesei mannosyl oligosaccharide 1,2-alpha-D
      mannosidase for N-glycan engineering in Pichia pastoris.
AB  - Therapeutic glycoprotein production in the widely used expression host Pichia
      pastoris is hampered by the differences in the protein-linked carbohydrate
      biosynthesis between this yeast and the target organisms such as man. A
      significant step towards the generation of human-compatible N-glycans in this
      organism is the conversion of the yeast-type high-mannose glycans to mammalian
      type high-mannose and/or complex glycans. In this perspective, we have co
      expressed an endoplasmic reticulum-targeted Trichoderma reesei 1,2-alpha-D
      mannosidase with two glycoproteins: influenza virus haemagglutinin and
      Trypanosoma cruzi trans-sialidase. Analysis of the N-glycans of the two purified
      proteins showed a >85% decrease in the number of alpha-1,2-linked mannose
      residues. Moreover, the human-type high-mannose oligosaccharide Man(5)GlcNAc(2)
      was the major N-glycan of the glyco-engineered trans-sialidase, indicating that N
      glycan engineering can be effectively accomplished in P. pastoris.

PMID- 11513878
TI  - Enhanced expression of human ABC-transporter tap is associated with cellular
      resistance to mitoxantrone.
AB  - Multidrug resistance (MDR) phenotypes have been associated with the
      overexpression of various members of the superfamily of ATP binding cassette
      (ABC) transporters. Here we demonstrate that a member of the ABC-transporter
      family, the heterodimer 'transporter associated with antigen processing' (TAP),
      physiologically involved in major histocompatibility complex class I-restricted
      antigen presentation, is significantly overexpressed in the human gastric
      carcinoma cell line EPG85-257RNOV exhibiting a mitoxantrone-resistant phenotype.
      This tumor cell line shows an atypical MDR phenotype in the absence of 'P
      glycoprotein' or 'MDR-associated protein' overexpression but with an enforced
      'breast cancer resistance protein' expression level. Transfection of both TAP
      subunits encoding cDNA molecules, TAP1 and TAP2, into the drug-sensitive parental
      gastric carcinoma cell line EPG85-257P conferred a 3.3-fold resistance to
      mitoxantrone but not to alternative anti-neoplastic agents. Furthermore, cell
      clones transfected with both, but not singularly expressed TAP1 or TAP2, reduced
      cellular mitoxantrone accumulation. Taken together, the data suggest that the
      heterodimeric TAP complex possesses characteristics of a xenobiotic transporter
      and that the TAP dimer contributes to the atypical MDR phenotype of human cancer
      cells.

PMID- 11513879
TI  - Molecular identification of phenylalanine ammonia-lyase as a substrate of a
      specific constitutively active Arabidopsis CDPK expressed in maize protoplasts.
AB  - Phenylalanine ammonia-lyase (PAL) is a key enzyme in pathogen defence, stress
      response and secondary metabolism and is subject to post-translational
      phosphorylation. In order to address the significance of this phenomenon it is
      necessary to identify the protein kinase (PK) responsible and place it in its
      regulatory circuit. Using protoplast transient expression of Arabidopsis kinase
      genes coupled to immunocomplex kinase assay, it has been possible to screen for
      specific PAL kinase. We show here that AtCPK1 (calcium dependent PK), but not
      other closely related PKs could phosphorylate both a recombinant PAL protein and
      a peptide (SRVAKTRTLTTA) that is a site phosphorylated in vivo. Identification of
      the specific CDPK as a PAL kinase now opens up the possibility of exploring the
      calcium link in biotic stress signalling, salicylate and phytoalexin production
      as well as the significance of PAL phosphorylation. The protoplast transient
      expression system is a potentially powerful method to determine and screen for
      plant gene functions utilising genomic and proteomic data.

PMID- 11513880
TI  - Nitrotyrosine mimics phosphotyrosine binding to the SH2 domain of the src family
      tyrosine kinase lyn.
AB  - The nitration of tyrosine residues in protein occurs through the action of
      reactive oxygen and nitrogen species and is considered a marker of oxidative
      stress under pathological conditions. The most active nitrating species so far
      identified is peroxynitrite, the product of the reaction between nitric oxide and
      superoxide anion. Previously, we have reported that in erythrocytes peroxynitrite
      irreversibly upregulates lyn, a tyrosine kinase of the src family. In this study
      we investigated the possible role of tyrosine nitration in the mechanism of lyn
      activation. We found that tyrosine containing peptides modelled either on the C
      terminal tail of src kinases or corresponding to the first 15 amino acids of
      human erythrocyte band 3 were able to activate lyn when the tyrosine was
      substituted with 3-nitrotyrosine. The activity of nitrated peptides was shared
      with phosphorylated but not with unphosphorylated, chlorinated or scrambled
      peptides. Recombinant lyn src homology 2 (SH2) domain blocked the capacity of the
      band 3-derived nitrotyrosine peptide to activate lyn and we demonstrated that
      this peptide specifically binds the SH2 domain of lyn. We propose that
      nitropeptides may activate src kinases through the displacement of the
      phosphotyrosine in the tail from its binding site in the SH2 domain. These
      observations suggest a new mechanism of peroxynitrite-mediated signalling that
      may be correlated with the upregulation of tyrosine phosphorylation observed in
      several pathological conditions.

PMID- 11513881
TI  - The X-ray structure of yeast 5-aminolaevulinic acid dehydratase complexed with
      two diacid inhibitors.
AB  - The structures of 5-aminolaevulinic acid dehydratase complexed with two
      irreversible inhibitors (4-oxosebacic acid and 4,7-dioxosebacic acid) have been
      solved at high resolution. Both inhibitors bind by forming a Schiff base link
      with Lys 263 at the active site. Previous inhibitor binding studies have defined
      the interactions made by only one of the two substrate moieties (P-side
      substrate) which bind to the enzyme during catalysis. The structures reported
      here provide an improved definition of the interactions made by both of the
      substrate molecules (A- and P-side substrates). The most intriguing result is the
      novel finding that 4,7-dioxosebacic acid forms a second Schiff base with the
      enzyme involving Lys 210. It has been known for many years that P-side substrate
      forms a Schiff base (with Lys 263) but until now there has been no evidence that
      binding of A-side substrate involves formation of a Schiff base with the enzyme.
      A catalytic mechanism involving substrate linked to the enzyme through Schiff
      bases at both the A- and P-sites is proposed.

PMID- 11513882
TI  - Superoxide dismutase mutations of familial amyotrophic lateral sclerosis and the
      oxidative inactivation of calcineurin.
AB  - Approximately 10% of all familial cases of amyotrophic lateral sclerosis (fALS)
      are linked to mutations in the SOD1 gene, which encodes the copper/zinc
      superoxide dismutase (CuZnSOD). Recently, wild-type CuZnSOD was shown to protect
      calcineurin, a calcium/calmodulin-regulated phosphoprotein phosphatase, from
      inactivation by reactive oxygen species. We asked whether the protective effect
      of CuZnSOD on calcineurin is affected by mutations associated with fALS. For
      this, we monitored calcineurin activity in the presence of mutant and wild-type
      SOD. We found that the degree of protection against inactivation of calcineurin
      by different SOD mutants correlates with the severity of the phenotype associated
      with the different mutations, suggesting a potential role for calcineurin-SOD1
      interaction in the etiology of fALS.

PMID- 11513883
TI  - Proteasome inhibitors and immunosuppressive drugs promote the cleavage of eIF4GI
      and eIF4GII by caspase-8-independent mechanisms in Jurkat T cell lines.
AB  - Previously, we have shown that translation eukaryotic initiation factor (eIF) 4GI
      is cleaved during anti-Fas-mediated apoptosis. Here, we have investigated the
      effects of the proteasome inhibitors, MG132 and lactacystin, and the
      immunosuppressants, 2-amino-2[2-(4-octylphenyl)ethyl]-1,3,propane diol (FTY720)
      and cyclosporin A, on the integrity of eIF4GI and eIF4GII in T cells. Using wild
      type Jurkat T cells, we show that the proteasome inhibitors MG132 and lactacystin
      promote the cleavage of eIF4G, activate caspase-8 and caspase-3-like activities
      and decrease cell viability. Furthermore, MG132 also promotes the cleavage of
      eIF4G and the activation of caspase-3-like activity in a caspase-8-deficient
      Jurkat cell line which is resistant to anti-Fas-mediated apoptosis. Using
      specific anti-peptide antisera, we show that both eIF4GI and eIF4GII are cleaved
      in either cell line in response to MG132 and lactacystin. In response to such
      treatments, we demonstrate that the fragments of eIF4GI generated include those
      previously observed with anti-Fas antiserum together with a novel product which
      lacks the ability to interact with eIF4E. In contrast, cells treated with the
      immunosuppressants FTY720 and cyclosporin A appear to contain only the novel
      cleavage fragment of eIF4GI and to lack those characteristic of cells treated
      with anti-Fas antiserum. These data suggest that caspase-8 activation is not
      required for apoptosis and eIF4G cleavage mediated by proteasome inhibitors and
      immunosuppressants in human T cells.

PMID- 11513884
TI  - Tuning of the product spectrum of vanillyl-alcohol oxidase by medium engineering.
AB  - The flavoenzyme vanillyl-alcohol oxidase (VAO) catalyzes the conversion of 4
      alkylphenols through the initial formation of p-quinone methide intermediates.
      These electrophilic species are stereospecifically attacked by water to yield (R)
      1-(4'-hydroxyphenyl)alcohols or rearranged in a competing reaction to 1-(4'
      hydroxyphenyl)alkenes. Here, we show that the product spectrum of VAO can be
      controlled by medium engineering. When the enzymatic conversion of 4-propylphenol
      was performed in organic solvent, the concentration of the alcohol decreased and
      the concentration of the cis-alkene, but not the trans-alkene, increased. This
      change in selectivity occurred in both toluene and acetonitrile and was dependent
      on the water activity of the reaction medium. A similar shift in alcohol/cis
      alkene product ratio was observed when the VAO-mediated conversion of 4
      propylphenol was performed in the presence of monovalent anions that bind
      specifically near the enzyme active site.

PMID- 11513885
TI  - Nuclear gene transcription and chromatin in Trypanosoma brucei.
AB  - As in other eucaryotes, the nuclear genome in Trypanosoma brucei is organised
      into silent domains and active domains transcribed by distinct RNA polymerases.
      The basic mechanisms underlying eucaryotic gene transcription are conserved
      between humans and yeast, and understood in some detail in these cells.
      Meanwhile, relatively little is known about the transcription machinery, the
      chromatin templates or their interactions in trypanosomatids. Here, I discuss and
      compare nuclear gene transcription in T. brucei with transcription in other
      eucaryotes focusing in particular on mono-allelic transcription of genes that
      encode the variant surface glycoproteins.

PMID- 11513886
TI  - The pro region of Toxoplasma ROP1 is a rhoptry-targeting signal.
AB  - The rhoptries of Toxoplasma gondii are regulated secretory organelles involved in
      the invasion of host cells. Rhoptry proteins are synthesised as pre-pro-proteins
      that are processed first to pro-proteins upon entrance into the secretory
      pathway, then processed again to their mature forms late in the secretory
      pathway. The pro-mature processing site of the rhoptry protein ROP1 has been
      determined, paving the way for understanding the role of the pro region in
      rhoptry protein function. We demonstrate here that the ROP1 pro region is
      sufficient for targeting a reporter protein (amino acids 34-471 of the
      Trypanosoma brucei VSG117 protein) to the rhoptries. These results, together with
      our previous work showing that rhoptry targeting is unaffected by deletion of the
      pro region, indicate that the ROP1 protein contains at least two signals that can
      function in rhoptry targeting.

PMID- 11513887
TI  - Physiological and haematological consequences of a novel parasite on the red
      rumped swallow Hirundo daurica.
AB  - Parasite virulence has been hypothesised to increase with the degree of host
      sociality because highly social hosts have a greater probability of encountering
      horizontal transmission of parasites and experiencing infections with multiple
      strains of the same parasites than do solitary hosts. As compared with the
      defences of closely related social host species, we predicted that solitary hosts
      should have relatively weak defences against parasites, thus being relatively
      more affected when parasitised by a novel parasite. We tested this prediction by
      either experimentally infesting 12 nests of the solitarily nesting red-rumped
      swallow Hirundo daurica with 50 individuals of the generalist martin bug Oeciacus
      hirundinis or by fumigation of nine nests. Nestlings 13 days old from the
      parasite addition group experienced increased mortality, attained lower body mass
      and tended to have shorter tarsi compared to nestlings from fumigated nests.
      Surprisingly, nestlings from the parasite addition group had higher packed cell
      volume (cellular fraction of blood) and lower levels of heat shock proteins
      (HSP60) than nestlings from the fumigation group. A measure of immunocompetence
      was not significantly affected by treatment, but its magnitude was positively
      related to packed cell volume and negatively related to level of HSP60. Solitary
      hosts like the red-rumped swallow have weak immune responses and low levels of
      heat shock proteins when infested with ectoparasites while highly social hosts
      have strong immune responses and high levels of heat shock proteins when
      infested. These findings partially support the hypothesis that potential host
      species with weak defences are more susceptible to infection and the deleterious
      effects of evolving parasites than potential hosts with strong defences.

PMID- 11513888
TI  - Nested assemblages resulting from host size variation: the case of endoparasite
      communities in fish hosts.
AB  - Nested species subsets are a common pattern in many types of communities found in
      insular or fragmented habitats. Nestedness occurs in some communities of
      ectoparasites of fish, as does the exact opposite departure from random assembly,
      anti-nestedness. Here, we looked for nested and anti-nested patterns in the
      species composition of communities of internal parasites of 23 fish populations
      from two localities in Finland. We also compared various community parameters of
      nested and anti-nested assemblages of parasites, and determined whether
      nestedness may result simply from a size-related accumulation of parasite species
      by feeding fish hosts. Nested parasite communities were characterised by higher
      prevalence (proportion of infected fish) and intensities of infection (number of
      parasites per fish) than anti-nested communities; the two types of non-random
      communities did not differ with respect to parasite species richness, however. In
      addition, the correlation between fish size and the number of parasite species
      harboured by individual fish was much stronger in nested assemblages than in anti
      nested ones, where it was often nil. These results were shown not to be artefacts
      of sampling effort or host phylogeny. They apply to both assemblages of adult and
      larval parasites, which were treated separately. Since species of larval
      parasites are extremely unlikely to interact with one another in fish hosts, the
      establishment of nestedness appears independent of the potential action of
      interspecific interactions. The species composition of these parasite communities
      is not determined from within the community, but rather by the extrinsic
      influence of host feeding rates and how they amplify differences among parasite
      species in probabilities of colonisation or extinction. Nested patterns occur in
      parasite communities whose fish hosts accumulate parasites in a predictable
      fashion proportional to their size, whereas anti-nested communities occur in
      parasite communities whose fish hosts do not, possibly because of dietary
      specialisation preventing them from sampling the entire pool of parasite species
      available locally. Thus, nestedness in parasite communities may result from
      processes somewhat different from those generating nested patterns in free-living
      communities.

PMID- 11513889
TI  - Order and disorder in ectoparasite communities: the case of congeneric gill
      monogeneans (Dactylogyrus spp.).
AB  - The measure of order and disorder in the distribution of species in fragmented
      habitats proposed by Atmar and Patterson (Oecologia, 96 (1993) 373-82) was
      applied to investigate nested patterns of Dactylogyrus species parasitising the
      gills of roach. Organisation in dactylogyrid assemblages was investigated at
      three levels: (1) host populations between localities; (2) local host populations
      over seasons; and (3) individual hosts over one season within a local host
      population. Dactylogyrid assemblages showed nested patterns when analyses were
      conducted at the level of localities (among host populations) and at the level of
      seasons (among host populations within localities). The analysis at the level of
      hosts (infracommunities of parasites) revealed that nested pattern is not common.
      We suggest that nestedness may have a variety of causes and does not necessarily
      imply competition.

PMID- 11513890
TI  - Toxicity of cadmium and zinc to Diplostomum spathaceum (Trematoda: Diplostomidae)
      cercarial survival.
AB  - The toxicity of cadmium and zinc at concentrations ranging from 0.1 to 10000
      microg/l was investigated with cercariae of Diplostomum spathaceum at three
      temperatures (12, 20, 25 degrees C) and three levels of water hardness (distilled
      water, soft water, hard water). Under most environmental conditions survival of
      cercariae was reduced by increasing metal concentration. Increasing water
      hardness and decreasing water temperature caused an increase in the survival of
      both control and metal exposed cercariae. However, with decreasing temperature
      increased survival of metal-exposed cercariae above the control occurred at a
      number of low metal concentrations. Differences in the relative toxicity of
      cadmium and zinc to cercariae was dependent on the environmental conditions of
      exposure. The two heavy metals demonstrated little toxicity to cercariae during
      the period of maximum cercarial infectivity (0-5 h). The mechanisms of metal
      toxicity and their effects on cercarial survival are discussed.

PMID- 11513891
TI  - Characterisation of large and small subunit rRNA and mini-exon genes further
      supports the distinction of six Trypanosoma cruzi lineages.
AB  - It has been proposed that isolates of Trypanosoma cruzi, the agent of American
      trypanosomiasis, can be ordered into two primary phylogenetic lineages, first
      based on multilocus enzyme electrophoresis and random amplified polymorphic DNA,
      and subsequently based on the 24Salpha rRNA and mini-exon genes. Recent
      multilocus enzyme electrophoresis and random amplified polymorphic DNA data have
      additionally shown that the major multilocus enzyme electrophoresis/random
      amplified polymorphic DNA lineage II is further subdivided into five smaller
      lineages, designated IIa-IIe. In this study, the precise correspondence between
      the multilocus enzyme electrophoresis/random amplified polymorphic DNA and
      rRNA/mini-exon lineages was investigated. Using the 24Salpha rRNA and mini-exon
      markers in combination, five sets of strains were distinguished, corresponding to
      the multilocus enzyme electrophoresis/random amplified polymorphic DNA lineages
      I, IIa, IIc, IId and to lineages IIb/IIe together, respectively. The previous
      categorisation into only two primary lineages based on 24Salpha rRNA and mini
      exon characterisation is explained, in part, by the lack of representativeness of
      the breadth of T. cruzi diversity in earlier study samples. Additionally, a PCR
      assay based on a length-variable region of the 18S rRNA gene distinguished
      lineage IIe from lineage IIb. Thus, the six multilocus enzyme
      electrophoresis/random amplified polymorphic DNA lineages could be readily
      identified by combining data from the 24Salpha rRNA, mini-exon and 18S rRNA
      characterisation assays, further supporting the relevance of these genetic units
      for T. cruzi strain classification and subspecific nomenclature. The recently
      proposed groups T. cruzi I and T. cruzi II correspond to multilocus enzyme
      electrophoresis/random amplified polymorphic DNA lineages I and IIb,
      respectively. Our findings show that T. cruzi lineage characterisation based on a
      single marker (either mini-exon or 24Salpha rRNA) has insufficient resolution,
      and leads to important reinterpretations of recent epidemiological and
      evolutionary studies based on the oversimplified rRNA/mini-exon dichotomic
      classification of T. cruzi isolates.

PMID- 11513892
TI  - In vitro responses of praziquantel-resistant and -susceptible Schistosoma mansoni
      to praziquantel.
AB  - The resistance status of five praziquantel-susceptible and five praziquantel
      resistant isolates was confirmed by chemotherapy in CD(1) mice with 3 x 200mg/kg
      micronised praziquantel. Micronised praziquantel had higher efficacy than two
      other praziquantel formulations (prepared without milling). The five resistant
      isolates were less responsive to praziquantel than the five susceptible isolates
      (59-74% reduction in worm burden in resistant isolates compared with 92-100% in
      susceptible isolates). Observations were made on the in vitro responses of
      different stages of 10 isolates to praziquantel. There were different in vitro
      responses to praziquantel at the egg, miracidial, cercarial and adult stages of
      Schistosoma mansoni between praziquantel-resistant and praziquantel-susceptible
      isolates. There were differences in the response of resistant and susceptible
      isolates following exposure of freshly hatched miracidia to 10(-6)M praziquantel
      for 1 min and observing the percent change in shape. Using this test it should be
      possible to determine whether failed therapy in patients infected with S. mansoni
      is due to the presence of praziquantel-resistant worms. Similarly, by exposing
      freshly shed cercariae to 4 x 10(-7)M praziquantel and observing the percent of
      tail shedding over 80 min it should be possible to monitor for the presence of
      praziquantel-resistant worms in snails collected in the field.

PMID- 11513893
TI  - Analysis of developmentally regulated genes of the parasite Haemonchus contortus.
AB  - Differential regulation of gene expression in the development of Haemonchus
      contortus was analysed using RNA arbitrarily-primed PCR. A study of third-stage
      larval and adult H. contortus revealed large differences between the two stages;
      32 and 30% unique third-stage larval and adult RNA arbitrarily-primed PCR
      products, respectively. This finding is consistent with a high degree of
      differential gene expression between these developmental stages. A number of
      adult products were sequenced, revealing 11 molecules to be similar to deposits
      within sequence databases. Four other molecules that did not have significant
      similarity to sequences in the databases may represent developmentally regulated
      genes specific to H. contortus. Northern analysis of the putative adult-expressed
      molecules with homologues in the databases confirmed that four were expressed
      only in adults, while four were expressed in both stages, but had different sized
      transcripts. This may reflect differential splicing, or expression of closely
      related but different molecules at different life cycle stages. Two molecules
      were present in mRNA populations from both stages, suggesting these were false
      stage-associated molecules. No transcript was detected for one molecule by
      Northern analysis, probably due to low level of expression. In situ hybridisation
      analysis was used to localise expression of transcripts in the adult parasite, in
      particular, to gain some insight into the nature of those molecules with no known
      predicted function.

PMID- 11513894
TI  - Identification of an MCM4 homologue expressed specifically in the sexual stage of
      Plasmodium falciparum.
AB  - Mini-chromosome maintenance (MCM) proteins play an essential role in DNA
      replication initiation. We have isolated a novel gene encoding an MCM-like
      protein from the human malaria parasite Plasmodium falciparum using the
      vectorette technique. The gene has no introns and comprises an open reading frame
      encoding 1005 amino acid residues with a predicted Mr of 115 kDa. The encoded
      protein, termed PfMCM4, contains all conserved sequences in the MCM family and
      displays the highest homology to the Cdc54 (MCM4) of Saccharomyces cerevisiae.
      However, PfMCM4 possesses five unique amino acid inserts with sizes ranging from
      seven to 75 residues. Southern blotting of genomic DNA digests and chromosomal
      separations showed that the Pfmcm4 gene is present as a single copy per haploid
      genome and is located on chromosome 13. A 4000-nucleotide transcript of this gene
      is expressed specifically in the sexual erythrocytic stage, indicating that
      PfMCM4 may be involved in gametogenesis in which DNA is quickly replicated.

PMID- 11513895
TI  - Phylogenetic analysis of the Monocotylidae (Monogenea) inferred from 28S rDNA
      sequences.
AB  - The current classification of the Monocotylidae (Monogenea) is based on a
      phylogeny generated from morphological characters. The present study tests the
      morphological phylogenetic hypothesis using molecular methods. Sequences from
      domains C2 and D1 and the partial domains C1 and D2 from the 28S rDNA gene for 26
      species of monocotylids from six of the seven subfamilies were used. Trees were
      generated using maximum parsimony, neighbour joining and maximum likelihood
      algorithms. The maximum parsimony tree, with branches showing less than 70%
      bootstrap support collapsed, had a topology identical to that obtained using the
      maximum likelihood analysis. The neighbour joining tree, with branches showing
      less than 70% support collapsed, differed only in its placement of Heterocotyle
      capricornensis as the sister group to the Decacotylinae clade. The molecular tree
      largely supports the subfamilies established using morphological characters.
      Differences are primarily how the subfamilies are related to each other. The
      monophyly of the Calicotylinae and Merizocotylinae and their sister group
      relationship is supported by high bootstrap values in all three methods, but
      relationships within the Merizocotylinae are unclear. Merizocotyle is
      paraphyletic and our data suggest that Mycteronastes and Thaumatocotyle, which
      were synonymized with Merizocotyle after the morphological cladistic analysis,
      should perhaps be resurrected as valid genera. The monophyly of the Monocotylinae
      and Decacotylinae is also supported by high bootstrap values. The Decacotylinae,
      which was considered previously to be the sister group to the Calicotylinae plus
      Merizocotylinae, is grouped in an unresolved polychotomy with the Monocotylinae
      and members of the Heterocotylinae. According to our molecular data, the
      Heterocotylinae is paraphyletic. Molecular data support a sister group
      relationship between Troglocephalus rhinobatidis and Neoheterocotyle rhinobatidis
      to the exclusion of the other species of Neoheterocotyle and recognition of
      Troglocephalus renders Neoheterocotyle paraphyletic. We propose Troglocephalus
      incertae sedis. An updated classification and full species list of the
      Monocotylidae is provided.

PMID- 11513896
TI  - Characterisation of a beta-tubulin gene from the liver fluke, Fasciola hepatica.
AB  - This study represents the first beta-tubulin sequence from a trematode parasite,
      namely, the liver fluke, Fasciola hepatica. PCR of genomic DNA showed that at
      least one beta-tubulin gene from F. hepatica contains no introns. A number of
      amino acids in the primary sequence of fluke tubulin are different from those
      described previously in various nematode species and the cestode, Echinococcus
      multilocularis. beta-Tubulin is an important target for benzimidazole
      anthelmintics, although (with the exception of triclabendazole) they show limited
      activity against F. hepatica. The amino acid differences in fluke beta-tubulin
      are discussed in relation to the selective toxicity of benzimidazoles against
      helminths and the mechanism of drug resistance.

PMID- 11513897
TI  - Eimeria necatrix virus: intracellular localisation of viral particles and
      proteins.
AB  - The presence of the Eimeria necatrix virus was investigated in the following life
      cycle stages: sporocysts, sporozoites, merozoites, and macrogametes. Electron
      microscopy revealed virus-like particles (VLPs) in sporozoites, which were
      purified from sporozoite extracts and used to raise polyclonal antibodies. Viral
      proteins were identified as RNA polymerase (95 kDa) and the major capsid protein
      (80 kDa). Polyclonal antibody was used to detect the intracellular localisation
      of VLPs and proteins. Immunoelectron microscopy and immunohistochemistry
      identified a viral protein of 95 kDa in all the E. necatrix stages studied,
      whereas the 80 kDa protein was found only in sporocysts and sporozoites. In
      addition, no VLPs were found in sporocysts. These results indicate that the
      synthesis of viral capsid proteins takes place during the early events of
      sporulation, and is then packaged into novel viruses during the late events. No
      VLPs were seen and no capsid proteins were found in the merozoites and
      macrogametes, whereas the 95 kDa RNA polymerase was present in both these stages.
      In addition, no VLPs or proteins were detected in chicken tissues.

PMID- 11513898
TI  - Malaria: a vaccine concept based on sickle haemoglobin's augmentation of an
      innate autoimmune process to band 3.
AB  - The protection from malaria afforded by sickle haemoglobin (and certain other
      haemoglobinopathies) suggests that it may be possible to utilise a common
      property that their erythrocytes share with both malaria-infected erythrocytes
      and senescent erythrocytes to develop a vaccine. All three conditions cause
      clustering of a specific protein molecule, band 3, on their erythrocyte's surface
      and this protein, when present on senescent erythrocytes at least, results in the
      immune recognition and removal of these by naturally occurring antibodies. It is
      hypothesised that if an up-regulated immune response to this protein on sickle
      cells is responsible for the benefit afforded to malaria patients then a vaccine
      using antigenic band 3 peptides may provide similar protection.

PMID- 11513899
TI  - Time to be serious about children's health care.

PMID- 11513900
TI  - Changes in notions about heart failure.

PMID- 11513901
TI  - Time to end health professional neglect of cycle of violence.

PMID- 11513902
TI  - Control of tuberculosis in Russia.

PMID- 11513903
TI  - Inflammation and Alzheimer's disease.

PMID- 11513904
TI  - Dealing with the pain of renal colic.

PMID- 11513905
TI  - Oestrogen-replacement therapy and risk of ovarian cancer.

PMID- 11513906
TI  - Prevalence of left-ventricular systolic dysfunction and heart failure in the
      Echocardiographic Heart of England Screening study: a population based study.
AB  - BACKGROUND: Accurate data for prevalence rates for heart failure due to various
      causes, and for left-ventricular systolic dysfunction in all adults are
      unavailable. Our aim was to assess prevalence of left-ventricular systolic
      dysfunction and heart failure in a large representative adult population in
      England. METHODS: Of 6286 randomly selected patients aged 45 years and older,
      3960 (63%) participated in the study. They came from 16 randomly selected general
      practices. We assessed patients by history and examination, electrocardiography,
      and echocardiography. Prevalence of left-ventricular systolic dysfunction
      (defined as ejection fraction <40%) and heart failure was calculated for the
      overall population on the basis of strict criteria and, when necessary,
      adjudication by a panel. FINDINGS: Left-ventricular systolic dysfunction was
      diagnosed in 72 (1.8% [95% CI 1.4-2.3]) participants, half of whom had no
      symptoms. Borderline left-ventricular function (ejection fraction 40-50%) was
      seen in 139 patients (3.5% [3.0-4.1]). Definite heart failure was seen in 92
      (2.3%, [1.9-2.8]) and was associated with an ejection fraction of less than 40%
      in 38 (41%) patients, atrial fibrillation in 30 (33%), and valve disease in 24
      (26%). Probable heart failure was seen in a further 32 (0.8% [0.6-1.1]) patients.
      In total, 124 (3.1% [2.6-3.7]) patients aged 45 years or older had definite or
      probable heart failure. INTERPRETATION: Heart failure is often misdiagnosed or
      underdiagnosed in primary care. Our results suggest that assessment of left
      ventricular function in patients with suspected heart failure could lead to more
      effective diagnosis and treatment of this disorder.

PMID- 11513907
TI  - Comparison of the effectiveness of WHO short-course chemotherapy and standard
      Russian antituberculous regimens in Tomsk, western Siberia.
AB  - BACKGROUND: There has been a resurgence of tuberculosis in Russia in the past
      decade. Traditional Russian services for treatment of tuberculosis are very
      different from those in the west. We aimed to compare the effects of WHO short
      course chemotherapy with standard Russian antituberculous regimens. METHODS: New
      tuberculosis patients aged 18 years or older were included in a trial and
      systematically allocated to traditional Russian tuberculosis treatments or WHO
      short-course chemotherapy in the two largest tuberculosis diagnostic and
      treatment centres of Tomsk Oblast, western Siberia. Standard WHO tuberculosis
      outcomes and rates of sputum conversion were used as primary outcomes. Analyses
      were by intention-to-treat. FINDINGS: 646 new cases were enrolled into the trial,
      of which 356 patients were given Russian tuberculosis treatment (155 smear
      positive) and 290 were given WHO short-course chemotherapy (155 smear positive).
      There was no statistical difference between the proportion cured or completing
      treatment (63% for both groups [difference in proportion=0%, 95% CI -11 to 11%]);
      or dying (short-course chemotherapy, 8% vs Russian, 11% [difference in
      proportion=-3%, 95% CI -9 to 4%]). There was no statistical difference with
      respect to sputum conversion rate at 6 months (91% vs 85% [difference in
      proportion=6%, 95% CI -2 to 13%]). Overall, outcomes were worse among patients
      with multidrug resistant isolates than non-resistant isolates. INTERPRETATIONS:
      WHO short-course chemotherapy treatment for tuberculosis can work well in Russia.

PMID- 11513908
TI  - Relation between childhood sexual and physical abuse and risk of revictimisation
      in women: a cross-sectional survey.
AB  - BACKGROUND: Women who are physically and sexually abused in childhood are at
      increased risk of victimisation in adulthood. Research has concentrated on sexual
      revictimisation, and has not included investigation of other abusive experiences,
      nor examination of prevalence and effects of abuse on adult revictimisation. We
      aimed to examine the relation between childhood trauma and adult revictimisation,
      and identify confounding factors. METHODS: We did a cross-sectional survey of
      2592 women who were attending primary care practices in east London, UK, with
      self-administered anonymous questionnaires. We included questions on physical and
      sexual abuse in childhood; on domestic violence, rape, indecent assault, and
      other traumatic experiences in adulthood; and on alcohol and other drug abuse. We
      analysed associations between childhood and adulthood abuse with multiple
      logistic regression. FINDINGS: 1207 (55%) of 2192 eligible women were recruited
      and completed the questionnaire. Abusive experiences co-occurred in both
      childhood and adulthood. Repetition and severity of childhood abuse were
      independently associated with specific types of adult revictimisation. Unwanted
      sexual intercourse (<16 years) was associated with domestic violence in adulthood
      (odds ratio 3.54; 95% CI 1.52-8.25) and with rape (2.84; 1.09-7.35); and severe
      beatings by parents or carers with domestic violence (3.58; 2.06-6.20), rape
      (2.70; 1.27-5.74), and other trauma (3.85; 2.23-6.63). INTERPRETATION: Childhood
      abuse substantially increases risk of revictimisation in adulthood. Women who
      have experienced multiple childhood abuse are at most risk of adult
      revictimisation. Identification of women who have undergone childhood abuse is a
      prerequisite for prevention of further abuse.

PMID- 11513909
TI  - Effect of hydroxychloroquine on progression of dementia in early Alzheimer's
      disease: an 18-month randomised, double-blind, placebo-controlled study.
AB  - BACKGROUND: Results of epidemiological studies, neuropathological observations,
      and in-vitro experiments all suggest that inflammatory mechanisms contribute to
      the destructive lesions in Alzheimer's disease. We aimed to establish the effect
      of the anti-inflammatory drug hydroxychloroquine on the progression of dementia.
      METHODS: We did a double-blind, parallel-group, multicentre trial in which we
      randomly assigned 168 patients with early Alzheimer's disease to
      hydroxychloroquine (200 or 400 mg dependent on bodyweight), or placebo for 18
      months. Outcome measures were related to activities of daily living, cognitive
      function, and behavioural abnormalities. Analysis was by intention to treat.
      RESULTS: At 18 months, mean scores for the interview for deterioration in daily
      life in dementia in patients on hydroxychloroquine (22.6 [SD 11.4]) did not
      differ from those for patients on placebo (21.3 [10.5]). Also, mean scores on the
      cognitive subscale of the Alzheimer's disease assessment scale were closely
      similar in hydroxychloroquine (26.4 [14.9]) and placebo (25.7 [14.3]) treated
      patients, as were behavioural changes, measured by the revised memory and
      behavioural problems checklist (36.3 [12.0] and 34.2 [12.4], respectively).
      Explorative analyses did not suggest any specific subgroup that benefited from
      hydroxychloroquine. The frequency and nature of serious adverse events and side
      effects were much the same in both groups. 155 (92%) patients completed all
      assessments over the entire study. INTERPRETATION: Anti-inflammatory treatment
      with hydroxychloroquine for 18 months does not slow the rate of decline in
      minimal or mild Alzheimer's disease.

PMID- 11513911
TI  - In-vivo measurement of activated microglia in dementia.
AB  - BACKGROUND: Activated microglia have a key role in the brain's immune response to
      neuronal degeneration. The transition of microglia from the normal resting state
      to the activated state is associated with an increased expression of receptors
      known as peripheral benzodiazepine binding sites, which are abundant on cells of
      mononuclear phagocyte lineage. We used brain imaging to study expression of these
      sites in healthy individuals and patients with Alzheimer's disease. METHODS: We
      studied 15 normal individuals (age 32-80 years), eight patients with Alzheimer's
      disease, and one patient with minimal cognitive impairment. Quantitative in-vivo
      measurements of glial activation were obtained with positron emission tomography
      (PET) and carbon-11-labelled (R)-PK11195, a specific ligand for the peripheral
      benzodiazepine binding site. FINDINGS: In normal individuals, regional [11C](R)
      PK11195 binding did not significantly change with age, except in the thalamus,
      where an age-dependent increase was found. By contrast, patients with Alzheimer's
      disease showed significantly increased regional [11C](R)-PK11195 binding in the
      entorhinal, temporoparietal, and cingulate cortex. INTERPRETATION: In-vivo
      detection of increased [11C](R)-PK11195 binding in Alzheimer-type dementia,
      including mild and early forms, suggests that microglial activation is an early
      event in the pathogenesis of the disease.

PMID- 11513912
TI  - Hearty hormones.

PMID- 11513913
TI  - Survival rate after early treatment for acute type-A aortic dissection with ACTH
      (1-24).
AB  - Haemorrhagic shock, usually as a consequence of major trauma, is the most
      frequent cause of death among people younger than 40 years. Reports indicate that
      melanocortin peptides are effective in reversing haemorrhagic shock. We found
      that in patients with aortic-dissection-induced haemorrhagic shock, the addition
      of an early intravenous bolus injection of the melanocortin andrenocorticotrophic
      hormone (ACTH)-(1-24) to standard treatment significantly improved cardiovascular
      function and increased survival rate. Because administration of ACTH-(1-24) is
      simple, and because melanocortin peptides have no acute toxicity, their use in
      the early critical care of patients in shock should be more extensively assessed.

PMID- 11513914
TI  - Use of McRoberts' position during delivery and increase in pushing efficiency.
AB  - McRoberts' position is used during the second stage of labour to facilitate
      delivery of the fetal shoulders. Few clinical studies have been done to measure
      its efficacy. We measured intrauterine pressure in 22 women in term labour, after
      the vertex reached 3+ station, in the dorsal lithotomy position. Patients pushed
      with legs either in stirrups or hyperflexed by 1358 (McRoberts' position).
      Maternal valsalva transiently increased the expulsive force by 32% over naturally
      occurring contractions. Use of McRoberts' position almost doubled the
      intrauterine pressure developed by contractions alone (from 1653 mm Hg s to 3262
      mm Hg s [97%]).

PMID- 11513915
TI  - Telomere shortening in atherosclerosis.
AB  - Eukaryotic chromosomes end with telomeres, which shorten with cellular ageing. We
      investigated whether atherosclerosis is associated with systemic evidence of
      accelerated cellular ageing. We compared mean length of terminal restriction
      fragments (TRF), a measure of average telomere size, in leucocyte DNA of ten
      patients with severe coronary artery disease (CAD) with that of 20 controls
      without CAD. Adjusting for age and sex, cases had mean TRF lengths of 303 (SD 90)
      base pairs shorter than those of controls (p=0.002)-ie, equivalent in size to
      individuals with no CAD who are 8.6 years older. Although this is a pilot study,
      the findings could be relevant to the pathogenesis of atherosclerosis.

PMID- 11513916
TI  - The incidence of out-of-hospital ventricular fibrillation in Helsinki, Finland,
      from 1994 to 1999.
AB  - Early defibrillation by emergency medical services has been a success story in
      the treatment of ventricular fibrillation. This success has been followed by
      recommendations to allow public access to defibrillation equipment. We tracked
      the changes in incidence of ventricular fibrillation from prospectively collected
      data from the Helsinki Cardiac Arrest Register. We found that the incidence of
      out-of-hospital ventricular fibrillation of cardiac origin fell by 48% from 1994
      to 1999 (p=0.0036). The primary and secondary prevention of coronary artery
      disease may not be the only reasons for this change and so new public-access
      defibrillation programmes should be delayed until our findings are confirmed.

PMID- 11513917
TI  - Researchers turn human stem cells into heart tissue.

PMID- 11513923
TI  - Dust clouds implicated in spread of infection.

PMID- 11513924
TI  - Alternatives to treatment in the UK.

PMID- 11513927
TI  - US House passes patients' bill of rights.

PMID- 11513928
TI  - UN health workers investigate polio outbreak in south Sudan.

PMID- 11513929
TI  - Kenyan government survey reveals poor state of public hospitals.

PMID- 11513930
TI  - Uganda's drug regulatory agency faces financial crisis.

PMID- 11513933
TI  - Qualitative research: standards, challenges, and guidelines.
AB  - Qualitative research methods could help us to improve our understanding of
      medicine. Rather than thinking of qualitative and quantitative strategies as
      incompatible, they should be seen as complementary. Although procedures for
      textual interpretation differ from those of statistical analysis, because of the
      different type of data used and questions to be answered, the underlying
      principles are much the same. In this article I propose relevance, validity, and
      reflexivity as overall standards for qualitative inquiry. I will discuss the
      specific challenges in relation to reflexivity, transferability, and shared
      assumptions of interpretation, which are met by medical researchers who do this
      type of research, and I will propose guidelines for qualitative inquiry.

PMID- 11513935
TI  - Antisense therapy in oncology: new hope for an old idea?
AB  - There is a potential role for antisense oligonucleotides in the treatment of
      disease. The principle of antisense technology is the sequence-specific binding
      of an antisense oligonucleotide to target mRNA, resulting in the prevention of
      gene translation. The specificity of hybridisation makes antisense treatment an
      attractive strategy to selectively modulate the expression of genes involved in
      the pathogenesis of diseases. One antisense drug has been approved for local
      treatment of cytomegalovirus-induced retinitis, and several antisense
      oligonucleotides are in clinical trials, including oligonucleotides that target
      the mRNA of BCL2, protein-kinase-C alpha, and RAF kinase. Antisense
      oligonucleotides are well tolerated and might have therapeutic activity. Here, we
      summarise treatment ideas in this field, summarise clinical trials that are being
      done, discuss the potential contribution of CpG motif-mediated effects, and look
      at promising molecular targets to treat human cancer with antisense
      oligonucleotides.

PMID- 11513936
TI  - Changing the way we address severe malnutrition during famine.
AB  - This year, yet again, saw widespread food insecurity and famine across the horn
      of Africa. Again, humanitarian agencies set up operations to implement various
      relief programmes. Nutritional interventions included general ration distribution
      to the whole of an affected population; blanket supplementary feeding to all
      members of an identified risk group; and targeted dry supplementary feeding
      centres for moderately malnourished and therapeutic feeding centres for the
      severely malnourished. As is usual in emergencies, many of the therapeutic
      feeding centres were hard to set up and did not achieve an adequate coverage of
      all the severely malnourished. This combination of delays and low coverage meant
      that many therapeutic feeding centres achieved little overall impact on
      mortality. I believe that the present focus on therapeutic feeding centres as the
      sole mode of treating severely malnourished people during famine is inappropriate
      and often counter-productive. A new concept of community-based therapeutic care
      is necessary to complement therapeutic feeding centres' interventions if famine
      relief programmes are to address the plight of the severely malnourished in an
      efficient and effective manner. During an emergency, the community-based
      therapeutic care approach could quickly provide good coverage and appropriate
      treatment for large numbers of severely malnourished people. The principles
      behind community-based therapeutic care are, however, developmental, empowering
      communities to cope more effectively with crisis and with transition back to
      normality. This is very different to the therapeutic feeding centres' approach
      that disempowers communities, requires very large amounts of external staff and
      resources, and undermines the infrastructure. Although emergency community-based
      therapeutic care programmes could be large-scale and implemented quickly, they
      could also evolve into developmental Hearth model nutritional programmes without
      changing their conceptual basis. Conversely, Hearth programmes, although largely
      sustainable, could in times of crisis quickly scale-up into rapid effective
      emergency interventions. Creating such a continuum between emergency and
      developmental approaches has long been a holy grail of humanitarianism.

PMID- 11513942
TI  - Comparison of wheat germ agglutinin-horseradish peroxidase and biotinylated
      dextran for anterograde tracing of corticospinal tract following spinal cord
      injury.
AB  - Established methods for monitoring regeneration of the corticospinal tract
      involve anterograde labelling of the cortical motor neuron. While wheat germ
      agglutinin-horseradish peroxidase conjugate has been used to anterogradely label
      these neurons, we demonstrate that this technique may not completely label the
      whole axon and fine terminal processes when this tracer is administered in dried
      form. An alternative method is described for anterograde labelling of cortical
      motor neurons using biotinylated dextran. This tracer may be applied by either
      microinjection of 10% biotinylated dextran or implanting small globules of the
      dried tracer into the motor cortex. While more laborious, microinjection results
      in better anterograde labelling than implantation of dried biotinylated dextran.
      A procedure is also described for preparing serial coronal sections through the
      entire spinal cord and thaw-mounted on a minimum number of slides. The labelled
      nerve processes in these tissue sections can be visualised in the spinal cord
      under a fluorescent microscope following incubation with cy3-streptavidin
      complex. Permanent labelling of the biotinylated nerve processes is achieved by
      incubation of tissue sections with streptavidin-horseradish peroxidase conjugate
      followed by stringent washes and staining with tetramethylbenzidine. Use of
      tetramethylbenzidine allows resolution of a greater number of finer labelled
      processes than diaminobenzindine and allows clear visualisation of individual
      regenerating corticospinal tract processes. Using these procedures, we
      demonstrate that the corticospinal tract is completely lesioned by a standardised
      contusion spinal cord injury produced by the New York University weight-drop
      device.

PMID- 11513943
TI  - Determination of serotonin in microdialysis samples from rat brain by microbore
      column liquid chromatography with post-column derivatization and fluorescence
      detection.
AB  - The present paper describes a new method for on-line determination of 5-HT in
      brain microdialysates from awake rats by microbore column liquid chromatography
      with post-column derivatization and fluorescence detection. The derivatization
      reagent contained 1 mM benzylamine and 0.5 mM potassium hexacyanoferrate (III),
      both dissolved in a mixture of acetonitrile and 25 mM borate buffer (pH 11.0)
      (1:1, v/v). The limit of detection (S/N=3) for 5-HT was 0.5 fmol/20 microl. The
      samples were injected every 20 min onto a microbore column packed with C18 silica
      gel. The method exhibits an excellent stability over the periods of at least 12
      24 h. The basal levels of 5-HT from 25 awake rats were 7.10+/-1.06 fmol/20 microl
      in the dorsal hippocampus and 4.64+/-0.91 fmol/20 microl (mean+/-SD) in the
      striatum. The 5-HT release increased to about 1500% during the perfusion with 100
      mM K(+) containing Ringer solution or it was reduced to 60 or 40% during the
      perfusion with 1 microM tetrodotoxin or calcium free Ringer, respectively. The
      new method can be used to monitor extracellular 5-HT following acute systemic
      drug administration.

PMID- 11513944
TI  - The use of control theory for the design of voltage clamp systems: a simple and
      standardized procedure for evaluating system parameters.
AB  - Voltage clamp (VC) instruments are closed-loop control systems based on
      electronic feedback. Such feedback systems can be described in the framework of
      control theory. We used a mathematical approach based on control theory to
      improve the performance of VC systems. This approach considerably simplifies the
      design and optimal tuning of these systems, as is demonstrated for a standard two
      electrode and a time-sharing single electrode clamp system. The major advantage
      of this approach and the consequent optimization procedure is that only
      proportional-integral controllers for VC systems must be used. As a consequence,
      the design of such VC systems is solely based on the time constants of the clamp
      circuit. In our approach, the 'symmetrical optimum' rule was applied for the
      first time to VC systems. This yields optimized systems with respect to speed of
      response and clamp accuracy. An empirical procedure has been derived from this
      theoretical approach which allows the optimal tuning of VC instruments based on
      PI controllers while running an experiment.

PMID- 11513945
TI  - Natural segmentation of the locomotor behavior of drug-induced rats in a
      photobeam cage.
AB  - Recently, Drai et al. (J Neurosci Methods 96 (2000) 119) have introduced an
      algorithm that segments rodent locomotor behavior into natural units of 'staying
      in place' (lingering) behavior versus going between places (progression
      segments). This categorization, based on the maximum speed attained within the
      segment, was shown to be intrinsic to the data, using the statistical method of
      Gaussian Mixture Model. These results were obtained in normal rats and mice using
      very large (650 or 320 cm) circular arenas and a video tracking system. In the
      present study, we reproduce these results with amphetamine, phencyclidine and
      saline injected rats, using data measured by a standard photobeam tracking system
      in square 45 cm cages. An intrinsic distinction between two or three 'gears'
      could be shown in all animals. The spatial distribution of these gears indicates
      that, as in the large arena behavior, they correspond to the difference between
      'staying in place' behavior and 'going between places'. The robustness of this
      segmentation over arena size, different measurement system and dose of two
      psychostimulant drugs indicates that this is an intrinsic, natural segmentation
      of rodent locomotor behavior. Analysis of photobeam data that is based on this
      segmentation has thus a potential use in psychopharmacology research.

PMID- 11513946
TI  - An in vitro temporomandibular joint-nerve preparation for pain study in rats.
AB  - A novel in vitro TMJ-nerve preparation was developed to quantitatively study
      peripheral sensory mechanisms of temporomandibular joint (TMJ). The TMJ region on
      one side (including mandibular head, disc, retrodiscal tissue and mandibular
      fossa) of adult Wistar albino rats was excised together with the auriculo
      temporal nerve. The block was preserved in a modified Krebs-Henseleit solution
      saturated with O(2)/CO(2) (95/5%) gas mixture. Using a calibrated von Frey type
      apparatus, mechanical noxious stimulation was applied directly to various sites
      within the TMJ region. In addition, thermal and chemical noxious stimuli were
      also attempted. Stable recordings of single unit activities from the auriculo
      temporal nerve could be obtained for as long as 5 h, which was sufficient to
      analyze the response properties of the TMJ units to various stimuli. This new
      preparation would be useful for investigating TMJ peripheral sensory mechanisms,
      especially pain, and potentially makes it possible to reveal neural mechanisms of
      temporomandibular arthralgia, a syndrome that has recently shown an increased
      incidence in clinical dentistry.

PMID- 11513947
TI  - A novel food-delivery device for neurophysiological and neuropsychological
      studies in monkeys.
AB  - Neurophysiological and neuropsychological studies in monkeys sometimes require an
      automated food-pellet dispenser. Commercially available dispensers typically
      sequester the pellet until delivery and, once delivered, the pellet's
      availability cannot be controlled. The custom-designed dispenser described here
      overcomes those two limitations. The device is composed of two separate units: a
      feeder and an electronic controller. The feeder manipulates food pellets with
      actuators driven by air pressure and delivers them into a serving bowl. The
      controller's settings determine whether the monkey can retrieve a pellet from the
      bowl. If the experiment requires that the pellet be visible and within reach, but
      unavailable for retrieval, the controller enables a trap-door mechanism at the
      bottom of the bowl. Any motion near the serving bowl, such as that caused by the
      approach of a monkey's hand, will then trigger the opening of the trap door,
      which causes the pellet to fall into an enclosed pellet collector. This rapid
      pellet-removal mechanism can also be triggered by other computer-controlled
      contingencies. Two of these dispensers have been in operation in an applied
      laboratory setting for over 2 years.

PMID- 11513948
TI  - Stimulus artifact removal using a software-based two-stage peak detection
      algorithm.
AB  - The analysis of stimulus evoked neuromuscular potentials or m-waves is a useful
      technique for improved feedback control in functional electrical stimulation
      systems. Usually, however, these signals are contaminated by stimulus artifact. A
      novel software technique, which uses a two-stage peak detection algorithm, has
      been developed to remove the unwanted artifact from the recorded signal. The
      advantage of the technique is that it can be used on all stimulation artifact
      contaminated electroneurophysiologic data provided that the artifact and the
      biopotential are non-overlapping. The technique does not require any estimation
      of the stimulus artifact shape or duration. With the developed technique, it is
      not necessary to record a pure artifact signal for template estimation, a process
      that can increase the complexity of experimentation. The technique also does not
      require the recording of any external hardware synchronisation pulses. The method
      avoids the use of analogue or digital filtering techniques, which endeavour to
      remove certain high frequency components of the artifact signal, but invariably
      have difficulty, resulting in the removal of frequencies in the same spectrum as
      the m-wave. With the new technique the signal is sampled at a high frequency to
      ensure optimum fidelity. Instrumentation saturation effects due to the artifact
      can be avoided with careful electrode placement. The technique was fully tested
      with a wide variety of electrical stimulation parameters (frequency and pulse
      width) applied to the common peroneal nerve to elicit contraction in the tibialis
      anterior. The program was also developed to allow batch processing of multiple
      files, using closed loop feedback correction. The two-stage peak detection
      artifact removal algorithm is demonstrated as an efficient post-processing
      technique for acquiring artifact free m-waves.

PMID- 11513949
TI  - An improved version of embolic model of brain ischemic injury in the rat.
AB  - A modified version of focal embolic stroke model has been developed in rats.
      Ischemic injury was induced by injection of a pre-formed clot into the middle
      cerebral artery (MCA). In the first series of experiments, the model was
      validated. Embolizing a pre-formed clot resulted in an infarction in the
      territory irrigated by the MCA. At 48 h after embolization, 2,3,5
      triphenyltetrazolium chloride (TTC) staining showed that infarction volume was
      42.1+/-15.6% (mean+/-S.D.) when 5 microl clot was injected (n=8) and 28.4+/-8.6%
      in the animals received 3.5 microl clot (n=8). The infarction volume between
      these two groups showed a significant difference (P<0.05). In the second series
      of experiments, the natural dissolution of the clot in the MCA was studied. Five
      min after embolization (n=6), clots were observed in the MCA of all the animals.
      Clots in the MCA were seen in 68 and 29% of the animals at 1 and 3 h,
      respectively, after embolization. These results suggest that the procedure
      described here produces a reliable and reproducible ischemic injury. The clots
      injected were dissolved in the MCA in relatively short period of time. The model
      shows a close similarity to thromboembolic stroke in human, and it provides a
      useful tool to investigate mechanisms and test thrombolytic agents in ischemic
      brain injury.

PMID- 11513950
TI  - Maintaining the cornea and the general physiological environment in visual
      neurophysiology experiments.
AB  - Neurophysiologists have been investigating the responses of neurons in the visual
      system for the past half-century using monkeys and cats that are anesthetized and
      paralyzed, with the non-blinking eyelids open for prolonged periods of time.
      Impermeable plastic contact lenses have been used to prevent dehydration of the
      corneal epithelium, which would otherwise occur in minutes. Unfortunately, such
      lenses rapidly introduce a variety of abnormal states that lead to clouding of
      the cornea, degradation of the retinal image, and premature termination of the
      experiment. To extend the viability of such preparations, a new protocol for
      maintenance of corneal health has been developed. The protocol uses rigid gas
      permeable contact lenses designed to maximize gas transmission, rigorous sterile
      methods, and a variety of methods for sustaining and monitoring the overall
      physiology of the animal. The effectiveness of the protocol was evaluated
      clinically by ophthalmoscopy before, during, and after the experiments, which
      lasted 8-10 days. Histopathology and quantitative histology were performed on the
      corneas following the experiment. Our observations showed that this protocol
      permits continuous contact lens wear without adversely affecting the corneas.
      Thus, it is possible to collect data 24 h each day, for the entire duration of
      the experiment.

PMID- 11513951
TI  - Rational selection and quantitative evaluation of antisense oligonucleotides.
AB  - Antisense oligonucleotides are an attractive therapeutic option to modulate
      specific gene expression. However, not all antisense oligonucleotides are
      effective in inhibiting gene expression, and currently very few methods exist for
      selecting the few effective ones from all candidate oligonucleotides. The lack of
      quantitative methods to rapidly assess the efficacy of antisense oligonucleotides
      also contributes to the difficulty of discovering potent and specific antisense
      oligonucleotides. We have previously reported the development of a prediction
      algorithm for identifying high affinity antisense oligonucleotides based on mRNA
      oligonucleotide hybridization. In this study, we report the antisense activity of
      these rationally selected oligonucleotides against three model target mRNAs
      (human lactate dehydrogenase A and B and rat gp130) in cell culture. The
      effectiveness of oligonucleotides was evaluated by a kinetic PCR technique, which
      allows quantitative evaluation of mRNA levels and thus provides a measure of
      antisense-mediated decreases in target mRNA, as occurs through RNase H
      recruitment. Antisense oligonucleotides that were predicted to have high affinity
      for their target proved effective in almost all cases, including tests against
      three different targets in two cell types with phosphodiester and
      phosphorothioate oligonucleotide chemistries. This approach may aid the
      development of antisense oligonucleotides for a variety of applications.

PMID- 11513952
TI  - Characterization of a nicotinamide nucleotide transhydrogenase gene from the
      green alga Acetabularia acetabulum and comparison of its structure with those of
      the corresponding genes in mouse and Caenorhabditis elegans.
AB  - Proton-pumping nicotinamide nucleotide transhydrogenase (Nnt) is a membrane-bound
      enzyme that catalyzes the reversible reduction of NADP(+) by NADH. This reaction
      is linked to proton translocation across the membrane. Depending on metabolic
      conditions, the enzyme may be involved in NADPH generation, e.g., for
      detoxification of peroxides and/or free radicals and protection from ischemic
      damage. Nnt exists in most prokaryotes and in animal mitochondria. It is composed
      of 2-3 subunits in bacteria and of a single polypeptide in mitochondria. An open
      question is whether Nnt exists in any photosynthetic eukaryotes and if so, to
      which class it belongs. In the present study it is demonstrated that, by cloning
      and sequencing cDNA and genomic copies of its NNT gene, an ancient alga,
      Acetabularia acetabulum (Chlorophyta, Dasycladales), contains a nuclear-encoded
      Nnt. In contrast to photosynthetic bacteria, this algal Nnt is composed of a
      single polypeptide of the class found in animal mitochondria. Excluding a poly(A)
      tail, NNT cDNA from A. acetabulum is 3688 bp long, consists of eight exons and
      spans 17 kb. The NNT gene from mouse was also characterized. Subsequently, the
      gene organization of the A. acetabulum NNT was compared to those of the
      homologous mouse (100 kb and 21 exons) and Caenorhabditis elegans (5.1 kb and 18
      exons) genes.

PMID- 11513953
TI  - Gene structure, chromosomal localization and analysis of 3-ketosteroid reductase
      activity of the human 3(alpha-->beta)-hydroxysteroid epimerase.
AB  - Following our previous characterization of the first human 3(alpha-
      >beta)hydroxysteroid epimerase (hHSE), we determined the genomic structure and
      chromosomal localization of the hHSE gene using fluorescent in situ hybridization
      (FISH) in this study. The gene spans 23 kb and contains five exons and four
      introns. FISH mapping assigned this gene to chromosome band 12q13. Primer
      extension analysis allowed the identification of a single transcription start
      site at 179 bp upstream from the ATG start codon. The 5'-flanking sequence lacks
      a typical TATA box in the proximal region of the transcription start site.
      However, analysis of the 2 kb promoter region revealed the presence of multiple
      potential transcription factor binding sites. Furthermore, we studied the 3
      ketosteroid reductase activity demonstrated by hHSE in intact cells stably
      expressing the enzyme. It has been known that, in vitro, 3beta-hydroxysteroid
      dehydrogenase (3beta-HSD) shows both oxidative and reductive activity. Our
      results showed that hHSE catalyzes the reduction of 3-ketosteroids to form 3beta
      hydroxysteroids while 3beta-HSD cannot catalyze this reaction in intact cells.
      However, hHSE showed 3-keto reductase activity in both microsomal fractions and
      intact cells. Since intact cells constitute a system which closely reflects in
      vivo intracellular conditions, we propose that hHSE might contribute to the
      cellular 3-ketosteroid reductase activity in the peripheral tissues.

PMID- 11513954
TI  - Identification of downstream target genes of latent membrane protein 1 in
      nasopharyngeal carcinoma cells by suppression subtractive hybridization.
AB  - Nasopharyngeal carcinoma (NPC) is a common cancer in Southern China and is
      closely associated with infection of Epstein-Barr virus (EBV). The EBV encoded
      latent membrane protein 1 (LMP1) is frequently detected in NPC and may play a
      role in its pathogenesis. Previous studies have shown that LMP1 transformed
      rodent fibroblasts and altered growth properties in B cells and epithelial cells.
      However, the pathological role of LMP1 in NPC cells is still poorly understood.
      In order to investigate the downstream target genes of LMP1 in NPC cells,
      suppression subtractive hybridization was used to clone and identify the genes
      differentially expressed in a LMP1 expressing NPC cell line, CNE-2. Two
      subtractive cDNA libraries were constructed: one enriched for the genes
      upregulated by LMP1 and one was for the genes downregulated by LMP1. A total of
      192 clones were screened by reverse Northern blotting. Fourteen of them were
      confirmed to be overexpressed while eight of them were suppressed. The
      upregulation of integrin alpha6, laminin 5gamma2, TAP1 and downregulation of
      p54nrb, RACK1 and p66Shc were further confirmed in three sets of LMP1 expressing
      NPC cell lines. The expression profiles of differentially expressed genes
      identified in this study suggest a role of LMP1 in promotion of cell survival and
      facilitation of tumor invasion.

PMID- 11513955
TI  - Molecular characterization of two novel alternative spliced variants of the KLRF1
      gene and subcellular distribution of KLRF1 isoforms.
AB  - The killer cell lectin-like receptor (KLR) family is formed by type II
      transmembrane glycoproteins with a single extracellular C-type lectin-like domain
      (CTLD). Some of these glycoproteins are involved in the regulation of natural
      killer cell activity. Recently, we have described the molecular characterization
      of the KLRF1 gene and the existence of one alternative spliced form, lacking the
      stalk region of the extracellular domain. In this work we describe two novel
      KLRF1 alternative spliced variants coding for truncated proteins lacking the
      CTLD. In addition, we present the biochemical analysis of the KLRF1 protein and
      the subcellular distribution of all KLRF1 isoforms expressed in heterologous
      transfectants.

PMID- 11513959
TI  - Effect of mutations in the upstream promoter on the transcription of human 5S
      rRNA genes.
AB  - The human 5S rRNA gene has a 12-mer external promoter, the D box, localized about
      30 bp upstream the coding sequence. By site directed mutagenesis 58 different D
      box promoter mutants were made. While some mutations in the D box allowed full
      transcription, other mutations decreased the transcriptional activity to 20-50%
      compared to the bona fide gene, showing the importance of this external promoter
      in transcription initiation. A number of maxi 5S rRNA genes were constructed from
      bona fide genes and D box mutated clones. Transfection of HeLa cells with maxi 5S
      rRNA genes showed that the D box is also important for 5S rRNA gene expression in
      vivo. Evidence from different eukaryotic cells suggests that expression of 5S
      rRNA genes is regulated by external promoters in addition to the internal control
      region.

PMID- 11513956
TI  - Isolation of a novel G-protein gamma-subunit from Arabidopsis thaliana and its
      interaction with Gbeta.
AB  - There is increasing evidence that heterotrimeric G-proteins (G-proteins) are
      involved in many plant processes including phytohormone response, pathogen
      defence and stomatal control. In animal systems, each of the three G-protein
      subunits belong to large multigene families; however, few subunits have been
      isolated from plants. Here we report the cloning of a second plant G-protein
      gamma-subunit (AGG2) from Arabidopsis thaliana. The predicted AGG2 protein
      sequence shows 48% identity to the first identified Arabidopsis Ggamma-subunit,
      AGG1. Furthermore, AGG2 contains all of the conserved characteristics of gamma
      subunits including a small size (100 amino acids, 11.1 kDa), C-terminal CAAX box
      and a N-terminal alpha-helix region capable of forming a coiled-coil interaction
      with the beta-subunit. A strong interaction between AGG2 and both the tobacco
      (TGB1) and Arabidopsis (AGB1) beta-subunits was observed in vivo using the yeast
      two-hybrid system. The strong association between AGG2 and AGB1 was confirmed in
      vitro. Southern and Northern analyses showed that AGG2 is a single copy gene in
      Arabidopsis producing two transcripts that are present in all tissues tested. The
      isolation of a second gamma-subunit from A. thaliana indicates that plant G
      proteins, like their mammalian counterparts, may form different heterotrimer
      combinations that presumably regulate multiple signal transduction pathways.

PMID- 11513958
TI  - Age-dependent changes of p57(Kip2) and p21(Cip1/Waf1) expression in skeletal
      muscle and lung of mice.
AB  - p57(Kip2) and p21(Cip1/Waf1) are members of cyclin-dependent kinase (Cdk)
      inhibitors which play critical roles in the terminal differentiation of skeletal
      muscle and lung. We investigated mRNA levels of p57(Kip2) and p21(Cip1/Waf1) in
      skeletal muscle and lung of mice during maturation and aging using Northern
      hybridization. The mRNA levels of p57(Kip2) and p21(Cip1/Waf1) decreased in
      skeletal muscle and lung of mice during maturation and aging except that the
      level of p21(Cip1/Waf1) mRNA in skeletal muscle of mice showed an increase only
      during maturation. The decrease of the p57(Kip2) mRNA level involved neither a
      change of DNA methylation at the promoter region nor an alteration of the
      imprinting status in aged mice. The decreases of p57(Kip2) and p21(Cip1/Waf1)
      mRNA levels during aging suggest that the process of tissue-specific terminal
      differentiation may be gradually downregulated with senescence in tissues where
      p57(Kip2) and p21(Cip1/Waf1) play key roles in differentiation. The
      downregulation of p57(Kip2) and p21(Cip1/Waf1) during aging is contrary to the
      upregulation of Cdk inhibitors during cellular replicative senescence, indicating
      that aging in an organismal level is mediated by mechanisms different from
      replicative senescence of cultured cells.

PMID- 11513957
TI  - Sequencing, phylogenetic and transcriptional analysis of the glyoxylate bypass
      operon (ace) in the halophilic archaeon Haloferax volcanii.
AB  - The glyoxylate cycle occurs in the three domains of living organisms: Eukarya,
      Bacteria and Archaea. We have isolated and sequenced the ace (acetate
      assimilation) gene operon, comprising the glyoxylate cycle key enzymes isocitrate
      lyase and malate synthase genes (icl or aceA and ms or aceB), from the halophilic
      archaeon Haloferax volcanii. This is the first time that these genes are
      sequenced in an organism from the domain Archaea. Phylogenetic analysis of the
      sequenced genes revealed that isocitrate lyase shows a significant identity with
      isocitrate lyases from Eukarya and Bacteria, but it is not more closely related
      to eukaryal or bacterial enzymes, and that malate synthase from H. volcanii has
      very little identity with any other known protein. This enzyme forms a new class
      of malate synthases. Transcriptional analysis indicated that both genes are
      cotranscribed in a single 2.7 kb mRNA molecule. The genes were transcribed only
      when acetate was the carbon source, indicating transcriptional regulation. Two
      sets of palindromic sequences were found in the promoter region, possibly
      involved in binding of transcriptional regulators (repressors and/or activators).

PMID- 11513960
TI  - Rainbow trout (Onchorhynchus mykiss) hepatic glucose transporter.
AB  - We report identification of a rainbow trout hepatic glucose transporter sharing
      58% and 52% amino acid identity with avian and mammalian GLUT2 sequences,
      respectively. The functionality of OnmyGLUT2 was assessed by expression in
      rainbow trout embryos. We also measured the transport of hexose in isolated
      rainbow trout hepatocytes. Inhibition of 3-O-methylglucose uptake by cytochalasin
      B, phloretin and 2-deoxy-D-glucose suggested the existence of a functional
      facilitative transporter in these cells. Expression of OnmyGLUT2 was found in the
      liver, kidney and intestine.

PMID- 11513962
TI  - Activation of spinach pullulanase by reduction results in a decrease in the
      number of isomeric forms.
AB  - Spinach starch debranching enzyme, a limit dextrinase or pullulanase (EC
      3.2.1.41), is a monomeric protein of 100 kDa that produces up to seven coexisting
      and mutually interconvertible isomers of different specific activity, a
      phenomenon that has been termed microheterogeneity and for which a structural
      explanation has not yet been presented. The enzyme can be activated by reduction,
      in particular by thiol reagents, and inactivated by oxidation and the concomitant
      change of the patterns of its isomeric forms could be quantified by
      chromatofocusing. The hypothesis was examined that reduction of the enzyme's
      thiol groups shifts the isomer pattern towards the forms with a higher specific
      activity while oxidation favours the less active forms. Using TCEP as reductant
      only the form with the highest specific activity was obtained. This form was
      almost inaccessible for proteolysis by trypsin while the oxidized and GSH
      activated enzyme yielded four peptides when treated with trypsin. Their sequence
      indicated cleavage predominantly of loops connecting the beta-strands and alpha
      helices of the (beta/alpha)(8)-barrel which forms the catalytic site of the
      pullulanase. Formation of various disulphide bridges between the loops connecting
      the barrel structures -- predominantly on one side -- may be the reason for the
      microheterogeneity of the spinach pullulanase. In vivo, the enzyme maintains its
      activated state due to the high concentration of GSH in the chloroplast. However,
      the chloroplast's pH shifts from day (pH 8) to night (pH 7) and thus could also
      alter the activity of the protein in accordance with the required function in
      starch metabolism.

PMID- 11513963
TI  - Wheat seed proteins exhibit a complex mechanism of protein elasticity.
AB  - Elastomeric proteins are found in a number of animal tissues (elastin, abductin
      and resilin), where they have evolved to fulfil a range of biological functions.
      All exhibit rubber-like elasticity, undergoing deformation without rupture,
      storing the energy involved in deformation, and then recovering to their initial
      state when the stress is removed. The second part of the process is passive,
      entropy decreasing when the proteins are deformed, with the higher entropy of the
      relaxed state providing the driving force for recoil. In plants there is only one
      well-documented elastomeric protein system, the alcohol-soluble seed storage
      proteins (gluten) of wheat. The elastic properties of these proteins have no
      known biological role, the proteins acting as a store for the germinating seed.
      Here we show that the modulus of elasticity of a group of wheat gluten subunits,
      when cross-linked by gamma-radiation, is similar to that of the cross-linked
      polypentapeptide of elastin. However, thermoelasticity studies indicate that the
      mechanism of elastic recoil is different from elastin and other characterized
      protein elastomers. Elastomeric force, f, has two components, an internal energy
      component, f(e), and an entropic component, f(s). The ratio f(e)/f can be
      determined experimentally; if this ratio is less than 0.5 the elastomeric force
      is predominantly entropic in origin. The ratio was determined as 5.6 for the
      cross-linked high M(r) subunits of wheat glutenin and near zero for the cross
      linked polypentapeptide of elastin. Tensile stress must be entropic or energetic
      in origin, the results would suggest that elastic recoil in the wheat gluten
      subunits, in part, may be associated with extensive hydrogen bonding within and
      between subunits and that entropic and energetic mechanisms contribute to the
      observed elasticity.

PMID- 11513961
TI  - Characterization and regulation of glutathione S-transferase gene from
      Schizosaccharomyces pombe.
AB  - A glutathione S-transferase (GST) gene has been cloned from Schizosaccharomyces
      pombe for the first time. The nucleotide sequence determined was found to contain
      2030 base pairs including an open reading frame of 229 amino acids that would
      encode a protein of a molecular mass of 27017 Da. The cloned GST gene was
      expressed and was found to function in S. pombe, Saccharomyces cerevisiae, and
      Escherichia coli. The plasmid pGT207 encoding the S. pombe GST gene appeared to
      be able to accelerate the growth of a wild type S. pombe culture. In a culture of
      S. pombe containing plasmid pGT207, the growth was inhibited less by mercuric
      chloride than in a culture with vector alone. The 1088 bp region upstream from
      the GST gene as well as the region encoding the N-terminal 14 amino acids was
      transferred into the promoterless beta-galactosidase gene of plasmid YEp357R to
      yield the fusion plasmid pYSH2000. beta-Galactosidase synthesis was induced by
      cadmium chloride, mercuric chloride, hydrogen peroxide, and menadione. It was
      also induced by high temperature. These results suggest that the cloned S. pombe
      GST gene is involved in the oxidative stress response.

PMID- 11513964
TI  - K(+)/Na(+) selectivity of the KcsA potassium channel from microscopic free energy
      perturbation calculations.
AB  - Microscopic molecular dynamics free energy perturbation calculations of the
      K(+)/Na(+) selectivity in the KcsA potassium channel, based on its experimental
      three-dimensional structure, are reported. The relative binding free energies for
      K(+) and Na(+) in the most relevant ion occupancy states of the four-site
      selectivity filter are calculated. The previously proposed mechanism for ion
      permeation through the KcsA channel is predicted, in agreement with available
      experimental data, to have a significant selectivity for K(+) over Na(+). The
      calculations also show that the individual 'binding site' selectivities are
      generally not additive and the doubly loaded states of the filter thus display
      cooperative effects. The only site that is not K(+) selective is that which is
      located at the entrance to the internal water cavity, suggesting the possibility
      that internal Na(+) could block outward currents.

PMID- 11513965
TI  - Conformational adjustments of SNase R and its N-terminal fragments probed by
      monoclonal antibodies.
AB  - Two monoclonal antibodies specific for staphylococcal nuclease R (SNase R)
      (McAb2C9 and McAb1B8) were prepared and used to probe protein folding during
      peptide elongation, by measuring antibody binding to seven N-terminal fragments
      (SNR141, SNR135, SNR121, SNR110, SNR102, SNR79 and SNR52) of SNase R. Comparative
      studies of the conformations of the N-terminal fragments have shown that all
      seven fragments of SNase R have a certain amount of residual structure,
      indicating that folding may occur during elongation of the nascent peptide chain.
      We show that the binding abilities of the intact enzyme and its seven fragments
      to the monoclonal antibodies are not simply proportional to the length of the
      peptide chain, suggesting that there may be continuous conformational adjustment
      in the nascent peptide chain as new C-terminal amino acids are added. A folding
      intermediate close in structure to the native state but with structural features
      in common with SNR121 is highly populated in 0.6 M GuHCl, and is also formed
      transiently during folding.

PMID- 11513966
TI  - Deflavination of flavo-oxidases by nucleophilic reagents.
AB  - Using spectroscopic techniques we studied the effect of the nucleophilic reagents
      cyanide, cyanate and thiocyanate on three flavo-oxidases namely alcohol oxidase
      (AO), glucose oxidase (GOX) and D-amino acid oxidase (DAOX). All three ions,
      added at concentrations in the mM range, caused release of the flavin adenine
      dinucleotide (FAD) co-factors from the enzyme molecules. In the case of AO this
      was accompanied by significant conformational perturbations, which was not
      observed for GOX and DAOX. As suggested from fluorescence, absorption and
      circular dichroism spectral changes at least one phenolic hydroxyl group became
      ionized upon FAD release from AO and a new class of Trp residues, fluorescent
      only in apo-AO protein, was demasked.

PMID- 11513967
TI  - Calcium-bindings of wild type and mutant troponin Cs of Caenorhabditis elegans.
AB  - Apparent Ca(2+)-binding constant (K(app)) of Caenorhabditis elegans troponin C
      (CeTnC) was determined by a fluorescence titration method. The K(app) of the N
      domain Ca(2+)-binding site of CeTnC was 7.9+/-1.6 x 10(5) M(-1) and that of the C
      domain site was 1.2+/-0.6 x 10(6) M(-1), respectively. Mg(2+)-dependence of the
      K(app) showed that both Ca(2+)-binding sites did not bind competitively Mg(2+).
      The Ca(2+) dissociation rate constant (k(off)) of CeTnC was determined by the
      fluorescence stopped-flow method. The k(off) of the N-domain Ca(2+)-binding site
      of CeTnC was 703+/-208 s(-1) and that of the C-domain site was 286+/-33 s(-1),
      respectively. From these values we could calculate the Ca(2+)-binding rate
      constant (k(on)) as to be 5.6+/-2.8 x 10(8) M(-1) s(-1) for the N-domain site and
      3.4+/-2.1 x 10(8) M(-1) s(-1) for the C-domain site, respectively. These results
      mean that all Ca(2+)-binding sites of CeTnC are low affinity, fast dissociating
      and Ca(2+)-specific sites. Evolutional function of TnC between vertebrate and
      invertebrate and biological functions of wild type and mutant CeTnCs are
      discussed.

PMID- 11513969
TI  - Tyrosinase action on monophenols: evidence for direct enzymatic release of o
      diphenol.
AB  - Using gas chromatography-mass spectrometry, the direct enzymatic release of o
      diphenol (4-tert-butylcatechol) during the action of tyrosinase on a monophenol
      (4-tert-butylphenol) has been demonstrated for the first time in the literature.
      The findings confirm the previously proposed mechanism to explain the action of
      tyrosinase on monophenols (J.N. Rodriguez-Lopez, J. Tudela, R. Varon, F. Garcia
      Carmona, F. Garcia-Canovas, J. Biol. Chem. 267 (1992)). Oxytyrosinase, the
      oxidized form of the enzyme with a peroxide group, is the only form capable of
      catalysing the transformation of monophenols into diphenols, giving rise to an
      enzyme-substrate complex in the process. The o-diphenol formed is then released
      from the enzyme-substrate complex or oxidized to the corresponding o-quinone. In
      order to detect the enzymatic release of o-diphenol, the non-enzymatic evolution
      of the o-quinone to generate o-diphenol by weak nucleophilic attack reactions and
      subsequent oxidation-reduction was blocked by the nucleophilic attack of an
      excess of cysteine. Furthermore, the addition of catalytic quantities of an
      auxiliary o-diphenol (e.g. catechol) considerably increases the accumulation of 4
      tert-butylcatechol. The enzyme acting on 4-tert-butylphenol generates the enzyme
      4-tert-butylcatechol complex and 4-tert-butylcatechol is then released (with k(
      2)) generating mettyrosinase. The auxiliary o-diphenol added (catechol) and the 4
      tert-butylcatechol generated by the enzyme then enter into competition. When
      [catechol] >> [4-tert-butylcatechol], the enzyme preferentially binds with the
      catechol to close the catalytic cycle, while 4-tert-butylcatechol is accumulated
      in the medium. In conclusion, we demonstrate that the enzyme produces 4-tert
      butylcatechol from 4-tert-butylphenol, the concentration of which increases
      considerably in the presence of an auxiliary o-diphenol such as catechol.

PMID- 11513968
TI  - Chemical modification of bacterial alpha-amylases: changes in tertiary structures
      and the effect of additional calcium.
AB  - A comparative study was performed on the effect of calcium on native and
      chemically modified forms of mesophilic and thermophilic alpha-amylases. Circular
      dichroism (CD) and irreversible thermoinactivation studies were carried out in
      the absence and presence of 10 mM calcium. From the CD experiments, changes in
      the tertiary structure of these enzymes, brought about by modification, were
      concluded. Furthermore, these changes were found to be influenced by the presence
      of calcium. Sorbitol was very effective in affording protection against
      irreversible thermoinactivation of native and modified forms of the enzymes, both
      in the absence and presence of calcium. Results are discussed in terms of the
      usefulness of this new approach involving a combination of medium and chemical
      modification for protein stabilization and enhancement of catalytic potential.

PMID- 11513970
TI  - Cooperative kinetics of human prostatic acid phosphatase.
AB  - The steady-state kinetics of hydrolysis reaction catalysed by human prostatic
      acid phosphatase (PAP) by using 1-naphthyl phosphate, phenyl phosphate and
      phosphotyrosine as substrates has been studied at pH 5.5. The substrate binding
      curves were sigmoidal and Hill cooperation coefficient h was higher than 1 for
      each of the examined compounds. Thus, human prostatic acid phosphatase kinetics
      exhibits positive cooperativity towards the studied substrates. The extent of
      cooperativity was found to depend on the substrate used and on enzyme
      concentration. The highest cooperativity of PAP was observed for 1-naphthyl
      phosphate and the lowest for phosphotyrosine. When prostatic phosphatase
      concentration increased, Hill cooperation coefficient (h) and half saturation
      constant (K(0.5)) both grew, but the catalytic constant (k(cat)) remained
      constant, for each of the substrates studied. Ligand-induced association
      dissociation equilibrium of the active oligomeric species (monomer-dimer-tetramer
      oligomers) is suggested.

PMID- 11513974
TI  - The effect of chitosan on stiffness and glycolytic activity of human bladder
      cells.
AB  - The cell's cytoskeleton together with the cell membrane and numerous accessory
      proteins determines the mechanical properties of cell. Any factors influencing
      cell organization and structure can cause alterations in mechanical properties of
      cell (its ability for deformation and adhesion). The determination of the local
      elastic properties of cells in their culture conditions has opened the
      possibility for the measurement of the influence of different factors on the
      mechanical properties of the living cells. The effect of the chitosan on the
      stiffness of the non-malignant transitional epithelial cells of ureter (HCV 29)
      and the transitional cell cancer of urine bladder (T24) was determined using
      scanning force microscopy. The investigations were performed in the culture
      medium (RPMI 1640) containing 10% fetal calf serum in the presence of the
      microcrystalline chitosan of the three different deacetylation degrees. In
      parallel, the effect of chitosan on production of lactate and ATP level was
      determined. The results showed the strong correlation between the decrease of the
      energy production and the increase in Young's modulus values obtained for the
      cancer cells treated with chitosan.

PMID- 11513972
TI  - Hyperosmotic stress activates the insulin receptor in CHO cells.
AB  - Stress factors, such as osmotic stress and genotoxic agents, activate stress
      kinases, whereas growth factors preferentially stimulate the structurally
      homologous mitogen-activated protein kinases, ERK1/2. Hyperosmolarity also has
      insulin-mimicking action as reflected by ERK1/2 activation and by the stimulation
      of glucose uptake in adipocytes. We examined to what extent hyperosmolarity
      activates components of the insulin receptor (IR) signalling pathway. CHO cells
      expressing the human IR were treated with 500 mM NaCl or 700 mM sorbitol and the
      activation of insulin signalling intermediates was studied. Hyperosmolarity
      induced tyrosine phosphorylation of the IR beta-subunit, and the adaptor proteins
      p52-Shc, p66-Shc, and IRS1. Furthermore, the stress kinases JNK and p38 were
      activated. When CHO cells were transfected with a kinase-dead IR (K1030R) mutant,
      hyperosmolarity did not induce tyrosine phosphorylation of the IR, indicating
      that hyperosmolarity induced IR autophosphorylation directly, rather than
      inducing phosphorylation by an exogenous tyrosine kinase. A partially purified
      and detergent-solubilized IR was not phosphorylated in response to
      hyperosmolarity, suggesting that hyperosmolarity activates the receptor only when
      present in the plasma membrane. In cells stably expressing the kinase-dead IR,
      IRS1 and Shc Tyr phosphorylation was abrogated, indicating that the
      hyperosmolarity signalling was dependent on an active IR tyrosine kinase. In
      contrast, the stress kinases p38 and JNK were normally activated by
      hyperosmolarity in the IR-K1030R mutant. We conclude that, at least in CHO cells,
      hyperosmolarity signals partially through IR autophosphorylation and subsequent
      activation of the IR downstream targets. This may be responsible for some of the
      insulin-mimicking effects of hyperosmolarity. The activation of stress kinases by
      hyperosmolarity occurs independent of the IR.

PMID- 11513976
TI  - The tubulogenic activity associated with an activated form of Flt-1 kinase is
      dependent on focal adhesion kinase.
AB  - Focal adhesion kinase (FAK) is known to be located at the intersection between
      extracellular matrix and growth factor signaling pathways to regulate cell
      motility. We have shown previously that an activated form (BCR-FLTm1) of Flt-1
      kinase, a receptor for vascular endothelial growth factor, had a tubulogenic
      activity not only in endothelial cells but also in fibroblastic cells. Here we
      show that tubulogenesis by BCR-FLTm1 depends on FAK and that FAK tyrosine
      phosphorylation and association with an activated Flt-1 receptor complex is
      increased after vascular endothelial growth factor stimulation of NIH3T3 cells
      overexpressing Flt-1.

PMID- 11513977
TI  - Homocysteine inhibits tumor necrosis factor-induced activation of endothelium via
      modulation of nuclear factor-kappa b activity.
AB  - Homocystinuria is a metabolic disorder associated with an increased incidence of
      vascular disease. Here, we analyzed the effects of homocysteine on endothelial
      cell activation that is a prerequisite for the recruitment of leukocytes to sites
      of evolving atherosclerotic plaques. Exposure of human umbilical vein endothelial
      cells to homocysteine alone did not modulate expression of the adhesion molecules
      E-selectin, intercellular adhesion molecule-1 and vascular cell adhesion molecule
      1, and the chemokines monocyte chemotactic protein-1 and interleukin-8. In
      contrast, tumor necrosis factor (TNF)-induced upregulation of these molecules was
      almost completely inhibited by homocysteine, but not by related thiol amino
      acids. Using electrophoretic mobility shift and reporter gene assays, the
      inhibitory effect of homocysteine could be attributed to inhibition of DNA
      binding and transcriptional activity of NF-kappa B. TNF-induced phosphorylation
      and degradation of I kappa B-alpha, however, were not affected. Neither was NF
      kappa B-independent activation of endothelial cells by interferon-gamma
      influenced by homocysteine. In summary, our data indicate that homocysteine
      alters the response to injury of endothelial cells which may have fundamental
      impacts on mechanisms of leukocyte recruitment to sites of inflammation. Our
      findings might refer to a novel pathway by which homocysteine is involved in
      vascular disorders associated with homocystinuria.

PMID- 11513973
TI  - Maitotoxin activates an endogenous non-selective cation channel and is an
      effective initiator of the activation of the heterologously expressed hTRPC-1
      (transient receptor potential) non-selective cation channel in H4-IIE liver
      cells.
AB  - The structures and mechanisms of activation of non-selective cation channels
      (NSCCs) are not well understood although NSCCs play important roles in the
      regulation of metabolism, ion transport, cell volume and cell shape. It has been
      proposed that TRP (transient receptor potential) proteins are the molecular
      correlates of some NSCCs. Using fura-2 and patch-clamp recording, it was shown
      that the maitotoxin-activated cation channels in the H4-IIE rat liver cell line
      admit Ca(2+), Mn(2+) and Na(+), have a high selectivity for Na(+) compared with
      Ca(2+), and are inhibited by Gd(3+) (half-maximal inhibition at 1 microM).
      Activation of the channels by maitotoxin was inhibited by increasing the
      extracellular Ca(2+) concentration or by inclusion of 10 mM EGTA in the patch
      pipette. mRNA encoding TRP proteins 1, 2 and 3 at levels comparable with those in
      brain was detected using reverse transcriptase-polymerase chain reaction in
      poly(A)(+) RNA prepared from H4-IIE cells and freshly-isolated rat hepatocytes.
      In H4-IIE cells transiently transfected with cDNA encoding hTRPC-1, the expressed
      hTRPC-1 protein was chiefly located at intracellular sites and at the plasma
      membrane. Cells expressing hTRPC-1 exhibited a substantial enhancement of
      maitotoxin-initiated Ca(2+) inflow and a modest enhancement of thapsigargin
      initiated Ca(2+) inflow (measured using fura-2) and no enhancement of the highly
      Ca(2+)-selective store-operated Ca(2+) current (measured using patch-clamp
      recording). In cells expressing hTRPC-1, maitotoxin activated channels which were
      not found in untransfected cells, have an approximately equal selectivity for
      Na(+) and Ca(2+), and are inhibited by Gd(3+) (half-maximal inhibition at 3
      microM). It is concluded that in liver cells (i) maitotoxin initiates the
      activation of endogenous NSCCs with a high selectivity for Na(+) compared with
      Ca(2+); (ii) TRP proteins 1, 2 and 3 are expressed; (iii) maitotoxin is an
      effective initiator of activation of heterologously expressed hTRPC-1 channels;
      and (iv) the endogenous TRP-1 protein is unlikely to be the molecular counterpart
      of the maitotoxin-activated NSCCs nor the highly Ca(2+)-selective store-operated
      Ca(2+) channels.

PMID- 11513975
TI  - Necrotic cell death by hydrogen peroxide in immortal DF-1 chicken embryo
      fibroblast cells expressing deregulated MnSOD and catalase.
AB  - The reactive oxygen species are known as endogenous toxic oxidant damaging
      factors in a variety of cell types, and in response, the antioxidant genes have
      been implicated in cell proliferation, senescence, immortalization, and
      tumorigenesis. The expression of manganese superoxide dismutase mRNA was shown to
      increase in most of the immortal chicken embryo fibroblast (CEF) cells tested,
      while expression of catalase mRNA appeared to be dramatically decreased in all
      immortal CEF cells compared to their primary counterparts. The expression of
      copper-zinc superoxide dismutase mRNA was shown to increase slightly in some
      immortal CEF cells. The glutathione peroxidase expressed relatively similar
      levels in both primary and immortal CEF cells. As primary and immortal DF-1 CEF
      cells were treated with 10-100 microM of hydrogen peroxide (concentrations known
      to be sublethal in human diploid fibroblasts), immortal DF-1 CEF cells were shown
      to be more sensitive to hydrogen peroxide, and total cell numbers were
      dramatically reduced when compared with primary cell counterparts. This increased
      sensitivity to hydrogen peroxide in immortal DF-1 cells occurred without evident
      changes in either antioxidant gene expression, mitochondrial membrane potential,
      cell cycle distribution or chromatin condensation. However, the total number of
      dead cells without chromatin condensation was dramatically elevated in immortal
      DF-1 CEFs treated with hydrogen peroxide, indicating that the inhibition of
      immortal DF-1 cell growth by low concentrations of hydrogen peroxide is due to
      increased necrotic cell death, but not apoptosis. Taken together, our observation
      suggests that the balanced antioxidant function might be important for cell
      proliferation in response to toxic oxidative damage by hydrogen peroxide.

PMID- 11513978
TI  - Disassembly of microtubules and inhibition of neurite outgrowth, neuroblastoma
      cell proliferation, and MAP kinase tyrosine dephosphorylation by dibenzyl
      trisulphide.
AB  - Dibenzyl trisulphide (DTS), a main lipophilic compound in Petiveria alliacea L.
      (Phytolaccaceae), was identified as one of the active immunomodulatory compounds
      in extracts of the plant. To learn more about its biological activities and
      molecular mechanisms, we conducted one-dimensional NMR interaction studies with
      bovine serum albumin (BSA) and tested DTS and related compounds in two well
      established neuronal cell-and-tissue culture systems. We found that DTS
      preferentially binds to an aromatic region of BSA which is rich in tyrosyl
      residues. In SH-SY5Y neuroblastoma cells, DTS attenuates the dephosphorylation of
      tyrosyl residues of MAP kinase (erk1/erk2). In the same neuroblastoma cell line
      and in Wistar 38 human lung fibroblasts, DTS causes a reversible disassembly of
      microtubules, but it did not affect actin dynamics. Probably due to the
      disruption of the microtubule dynamics, DTS also inhibits neuroblastoma cell
      proliferation and neurite outgrowth from spinal cord explants. Related dibenzyl
      compounds with none, one, or two sulphur atoms were found to be significantly
      less effective. These data confirmed that the natural compound DTS has a diverse
      spectrum of biological properties, including cytostatic and neurotoxic actions in
      addition to immunomodulatory activities.

PMID- 11513971
TI  - Expression and characterisation of the thrombospondin type I repeats of human
      properdin.
AB  - Properdin, an upregulator of the alternative complement pathway, is central to
      deposition of the activated complement fragment C3b on the surfaces of the
      pathogens, which it achieves by preventing the dissociation of the Bb catalytic
      subunit from the inherently labile C3bBb complexes. It is also known to bind
      sulphated glycoconjugates, such as sulphatides. Properdin has an unusual
      structure formed by oligomerisation of a rod-like monomer into cyclic dimers,
      trimers and tetramers. The monomer (approximately 53 kDa) contains an N-terminal
      region of no known homology, followed by six non-identical repeats of 60 amino
      acids (based on exon/intron boundaries), called 'thrombospondin type I repeats'
      or TSR modules. We have expressed and purified the N-terminal region and each of
      the individual TSR repeats in Escherichia coli. Although the individual
      recombinant TSRs, after a denaturation-renaturation cycle, appeared to be
      correctly folded modules, as judged by the one-dimensional (1D)- and 2D-nuclear
      magnetic resonance spectra of TSR3, they did not show binding to either C3b or
      sulphatide. Polyclonal antibodies were raised against each TSR and were found to
      be module-specific. The anti-TSR5 polyclonal antibody was found to inhibit
      binding of native human properdin to solid-phase C3b, or sulphatides. It could
      also block properdin-dependent haemolysis of rabbit erythrocytes. These results
      are consistent with the view that the TSR5 contains the major site in properdin
      which is involved in both C3b and sulphatide binding. It also suggests that a co
      operative intramolecular interaction between TSRs, as found in the native
      molecule, is required for TSR5 to bind either C3b or sulphatides.

PMID- 11513996
TI  - Bioinformatics -- a patenting view.
AB  - The use of bioinformatics in the biological sciences has brought about a change
      in the way that biological inventions can be protected by patent laws. Using
      approaches developed in the fields of computer science and business, patent
      applicants now seek to protect certain aspects of their inventions, which include
      software, methods of doing business and uses of information as well as more
      traditional biotechnological products and processes. These approaches are useful
      in resolving some of the difficulties now faced in prosecuting patent
      applications directed to biological inventions that are claimed in more
      conventional terms.

PMID- 11513997
TI  - The biotechnological control of pitch in paper pulp manufacturing.
AB  - At present, microbial and enzymatic preparations for the control of triglyceride
      containing pitch deposits during the manufacture of mechanical and sulfite paper
      is commercially available. However, biotechnological products for pitch control
      in other pulping processes, such as alkaline pulping, are under development.
      These products include new fungi for the removal of steroids involved in pitch
      deposit formation in chlorine-free pulps, to be used as a biological pretreatment
      of wood before pulping. Simultaneously, tailor-made enzymes are being produced
      using protein-engineering techniques, enabling the specific removal of pitch
      contaminant compounds from paper pulp.

PMID- 11514001
TI  - Assessing the environmental impacts of transgenic plants.

PMID- 11514003
TI  - Contralateral breast cancer risk.
AB  - The use of breast-conserving treatment approaches for breast cancer has now
      become a standard option for early stage disease. Numerous randomized studies
      have shown medical equivalence when mastectomy is compared to lumpectomy followed
      by radiotherapy for the local management of this common problem. With an
      increased emphasis on patient involvement in the therapeutic decision making
      process, it is important to identify and quantify any unforeseen risks of the
      conservation approach. One concern that has been raised is the question of
      radiation- related contralateral breast cancer after breast radiotherapy.
      Although most studies do not show statistically significant evidence that
      patients treated with breast radiotherapy are at increased risk of developing
      contralateral breast cancer when compared to control groups treated with
      mastectomy alone, there are clear data showing the amount of scattered radiation
      absorbed by the contralateral breast during a routine course of breast
      radiotherapy is considerable (several Gy) and is therefore within the range where
      one might be concerned about radiogenic contralateral tumors. While radiation
      related risks of contralateral breast cancer appear to be small enough to be
      statistically insignificant for the majority of patients, there may exist a
      smaller subset which, for genetic or environmental reasons, is at special risk
      for scatter related second tumors. If such a group could be predicted, it would
      seem appropriate to offer either special counseling or special prevention
      procedures aimed at mitigating this second tumor risk. The use of genetic
      testing, detailed analysis of breast cancer family history, and the
      identification of patients who acquired their first breast cancer at a very early
      age may all be candidate screening procedures useful in identifying such at- risk
      groups. Since some risk mitigation strategies are convenient and easy to utilize,
      it makes sense to follow the classic 'ALARA' (as low as reasonably achievable)
      principles and to minimize scattered radiation for these special risk groups and
      perhaps for all patients undergoing breast radiotherapy. This paper reviews the
      literature on the risk of radiation- related second contralateral breast cancers.

PMID- 11514002
TI  - The radiation overexposure of radiotherapy patients in Panama 15 June 2001.

PMID- 11514000
TI  - Challenge of psychrophilic anaerobic wastewater treatment.
AB  - Psychrophilic anaerobic treatment is an attractive option for wastewaters that
      are discharged at moderate to low temperature. The expanded granular sludge bed
      (EGSB) reactor has been shown to be a feasible system for anaerobic treatment of
      mainly soluble and pre-acidified wastewater at temperatures of 5--10 degrees C.
      An organic loading rate (OLR) of 10--12 kg chemical oxygen demand (COD) per cubic
      meter reactor per day can be achieved at 10--12 degrees C with a removal
      efficiency of 90%. Further improvement might be obtained by a two-module system
      in series. Stabile methanogenesis was observed at temperatures as low as 4--5
      degrees C. The specific activity of the mesophilic granular sludge was improved
      under psychrophilic conditions, which indicates that there was growth and
      enrichment of methanogens and acetogens in the anaerobic system. Anaerobic sewage
      treatment is a real challenge in moderate climates because sewage belongs to the
      'complex' wastewater category and contains a high fraction of particulate COD. A
      two-step system consisting of either an anaerobic up-flow sludge bed (UASB)
      reactor combined with an EGSB reactor or an anaerobic filter (AF) combined with
      an anaerobic hybrid reactor (AH) is successful for anaerobic treatment of sewage
      at 13 degrees C with a total COD removal efficiency of 50% and 70%, respectively.

PMID- 11514005
TI  - A glance on quality assurance in EORTC study 22922 evaluating techniques for
      internal mammary and medial supraclavicular lymph node chain irradiation in
      breast cancer.
AB  - PURPOSE: To evaluate the irradiation techniques used for the irradiation of the
      internal mammary and medial supraclavicular lymph node chain (IM-MS) in the EORTC
      22922 study, which evaluates its impact on survival in stage I-III breast cancer
      patients with axillary node invasion and/or central or medial location of the
      primary tumour. MATERIALS AND METHODS: The analysis was performed based on the
      dummy run data of the Quality Assurance Programme of the study. A standard
      irradiation technique was proposed within the study protocol, and the use of
      other treatment set-up techniques was allowed. RESULTS: By March 2000, 39 centres
      from 12 different countries had participated in the study; 32 of these had
      already fulfilled the dummy run procedure. No centres had to be excluded from the
      study. Seventy-eight percent of the centres are using the standard irradiation
      technique, 64% of these with minor variations. Twenty-two percent of the centres
      developed an alternative irradiation technique. The remarks to the centres using
      the standard set-up were most often related to the junction problem and the
      possible under- or overdosage in the target volumes. The remarks to the centres
      with alternative techniques most often concerned the possible enhanced dose to
      the lungs and the heart. CONCLUSION: In a multi-centre trial an easy irradiation
      technique applicable in a large number of centres should be provided. A quality
      assurance programme allows early detection of possible problems with treatment
      planning and delivery. The analysis of the dummy run data showed that if the
      recommendations of the Quality Assurance Committee are applied, both standard and
      alternative IM-MS irradiation techniques produce acceptable dose distributions.

PMID- 11513999
TI  - Protein--carbohydrate interactions: learning lessons from nature.
AB  - Protein--carbohydrate interactions are at the heart of many important biological
      processes including signalling, recognition and catalysis. A deeper understanding
      of these interactions at the molecular level will enable the development of
      novel, effective and highly selective therapeutics. Glycosyltransferases and
      glycosidases, carbohydrate-processing enzymes responsible for the synthesis and
      breakdown of oligosaccharides, have emerged as important targets in the fight
      against bacterial and fungal pathogenesis, cancer and AIDS. Binding and
      recognition phenomena are essential processes by which the body exerts control
      over complex biological functions. In this regard, heparin has retained ongoing
      interest reflecting its importance as a major pharmaceutical. Recent studies on
      heparin have shed light onto the mechanisms of cross-reactivity that cause life
      threatening side effects and have provided impetus for the development of more
      selective anti-clotting agents. Important targets for therapeutic intervention
      are the binding processes mediated through multivalent protein--carbohydrate
      interactions, such as the interactions of bacterial toxins with cell-surface
      receptors.

PMID- 11514004
TI  - Cardiac avoidance in breast radiotherapy: a comparison of simple shielding
      techniques with intensity-modulated radiotherapy.
AB  - BACKGROUND AND PURPOSE: Adjuvant breast radiotherapy (RT) is now part of the
      routine care of patients with early breast cancer. However, analysis of the Early
      Breast Cancer Trialists' Collaborative suggests that patients with the lowest
      risk of dying of breast cancer are at significant risk of cardiac mortality due
      to longer relapse-free survival. Patients with a significant amount of heart in
      the high-dose volume have been shown to be at risk of fatal cardiac events. This
      study was designed to assess whether conformal planning or intensity-modulated
      radiotherapy (IMRT) techniques allow reduced cardiac irradiation whilst
      maintaining full target coverage. MATERIAL AND METHODS: Ten patients with early
      breast cancer were available for computed tomography (CT) planning. Each had at
      least 1 cm maximum heart depth within the posterior border of conventional
      tangents. For each patient, plans were generated and compared using dose volume
      histograms for planning target volume (PTV) and organs at risk. The plans
      included conventional tangents with and without shielding. The shielding was
      designed to either completely spare the heart or to shield as much heart as
      possible without compromising PTV coverage. IMRT plans were also prepared using
      two- and four-field tangential and six-field arc-like beam arrangements. RESULTS:
      PTV homogeneity was better for the tangential IMRT techniques. For all patients,
      cardiac irradiation was reduced by the addition of partial cardiac shielding to
      conventional tangents, without compromise of PTV coverage. The two- and four
      field IMRT techniques also reduced heart doses. The average percentage volume of
      heart receiving >60% of the prescription dose was 4.4% (range 1.0-7.1%) for
      conventional tangents, 1.5% (0.2-3.9%) for partial shielding, 2.3% (0.5-4.6%) for
      the two-field IMRT technique and 2.2% (0.4-5.6%) for the four-field IMRT
      technique. For patients with larger maximum heart depths the four-field IMRT plan
      achieved greater heart sparing than the partial shielding, although irradiation
      of the contralateral breast was increased. Full cardiac shielding resulted in the
      most complete heart sparing but with compromise of the PTV coverage; the mean
      volume receiving less than 95% of the prescription dose was 4% (range 1.5-8.7%).
      CONCLUSION: All patients undergoing adjuvant tangential breast RT in whom the
      heart is seen to be in the high-dose volume should be considered for the addition
      of cardiac-sparing lead blocks. Three-dimensional CT planning and alternative
      beam arrangements with IMRT optimization enables more complete cardiac sparing
      without compromise of PTV coverage in certain patients.

PMID- 11513998
TI  - Genetic approaches to harvesting lichen products.
AB  - Lichens are symbiotic associations between fungi, green algae and/or
      cyanobacteria. They have a varied chemistry and produce many polyketide-derived
      compounds, including some, such as depsides and depsidones, that are rarely
      reported elsewhere. Although lichens have been appreciated in traditional
      medicines, their value has largely been ignored by the modern pharmaceutical
      industry because difficulties in establishing axenic cultures and conditions for
      rapid growth preclude their routine use in most conventional screening processes.
      Recently, molecular genetic techniques using PCR, genomic library construction
      and heterologous expression have provided an alternative approach to begin
      exploring the diversity of polyketide biosynthetic pathways in lichens. The
      techniques can be expanded to cover other pathway types and be integrated with
      conventional culture collection-based screening to provide a comprehensive search
      for novel chemical entities in these organisms.

PMID- 11514007
TI  - Inter fraction variations in rectum and bladder volumes and dose distributions
      during high dose rate brachytherapy treatment of the uterine cervix investigated
      by repetitive CT-examinations.
AB  - PURPOSE: To evaluate variation of dose to organs at risk for patients receiving
      fractionated high dose rate gynaecological brachytherapy by using CT-based 3D
      treatment planning and dose-volume histograms (DVH). MATERIALS AND METHODS:
      Fourteen patients with cancer of the uterine cervix underwent three to six CT
      examinations (mean 4.9) during their course of high-dose-rate brachytherapy using
      radiographically compatible applicators. The rectal and bladder walls were
      delineated and DVHs were calculated. RESULTS: Inter fraction variation of the
      bladder volume (CV(mean)=44.1%) was significantly larger than the inter fraction
      variation of the mean dose (CV(mean)=19.9%, P=0.005) and the maximum dose
      (CV(mean)=17.5%, P=0.003) of the bladder wall. The same trend was seen for
      rectum, although the figures were not significantly different. Performing CT
      examinations at four of seven brachytherapy fractions reduced the uncertainty to
      4 and 7% for the bladder and rectal doses, respectively. A linear regression
      analysis showed a significant, negative relationship between time after treatment
      start and the whole bladder volume (P=0.018), whereas no correlation was found
      for the rectum. For both rectum and bladder a linear regression analysis revealed
      a significant, negative relationship between the whole volume and median dose
      (P<0.05). CONCLUSION: Preferably a CT examination should be provided at every
      fraction. However, this is logistically unfeasible in most institutions. To
      obtain reliable DVHs the patients will in the future undergo 3-4 CT examinations
      during the course of brachytherapy at our institution. Since this study showed an
      association between large bladder volumes and dose reductions, the patients will
      be treated with a standardized bladder volume.

PMID- 11514009
TI  - Design and implementation of a system for treating paediatric patients with
      stereotactically-guided conformal radiotherapy.
AB  - BACKGROUND AND PURPOSE: Stereotactically-guided conformal radiotherapy (SCRT)
      allows the delivery of highly conformal dose distributions to localised brain
      tumours. This is of particular importance for children, whose often excellent
      long-term prognosis should be accompanied by low toxicity. The commercial
      immobilisation system in use at our hospital for adults was felt to be too heavy
      for children, and precluded the use of anaesthesia, which is sometimes required
      for paediatric patients. This paper therefore describes the design and
      implementation of a system for treating children with SCRT. This system needed to
      be well tolerated by patients, with good access for treating typical childhood
      malignancies. MATERIALS AND METHODS: A lightweight frame was developed for
      immobilisation, with a shell-based alternative for patients requiring general
      anaesthetic. Procedures were set up to introduce the patients to the frame system
      in order to maximise patient co-operation and comfort. Film measurements were
      made to assess the impact of the frame on transmission and surface dose. The
      reproducibility of the systems was assessed using electronic portal images.
      RESULTS: Both frame and shell systems are in clinical use. The frame weighs 0.6
      kg and is well tolerated. It has a transmission of 92-96%, and fields which pass
      through it deliver surface doses of 58-82% of the dose at d(max), compared to 18%
      when no frame is present. However, the frame is constructed to maximise the
      availability of unobstructed beam directions. Reproducibility measurements for
      the frame showed a mean random error of 1.0+/-0.2mm in two dimensions (2D) and
      1.4+/-0.7 mm in 3D. The mean systematic error in 3D was 2.2mm, and 90% of all
      overall 3D errors were less than 3.4mm. For the shell system, the mean 2D random
      error was 1.5+/-0.2mm. CONCLUSIONS: Two well-tolerated immobilisation devices
      have been developed for fractionated SCRT treatment of paediatric patients. A
      lightweight frame system gives a wide range of possible unobstructed beam
      directions, although beams that intersect the frame are not precluded, provided
      that output corrections are applied. A shell system allows the use of general
      anaesthesia. Both systems give reproducible immobilisation to complement the high
      precision treatment delivery.

PMID- 11514006
TI  - Pulmonary sequelae after electron spinal irradiation.
AB  - We measured pulmonary function in 21 patients, after craniospinal irradiation
      with a posterior spinal electron beam. The median age at treatment was 7.5 years.
      Nine patients (43%) demonstrated abnormal pulmonary function tests, five with
      restrictive changes, one with isolated diminished diffusion capacity, and three
      with obstructive disease. These changes were mild and predominantly asymptomatic.

PMID- 11514010
TI  - Impact of simple tissue inhomogeneity correction algorithms on conformal
      radiotherapy of lung tumours.
AB  - BACKGROUND AND PURPOSE: Conformal radiotherapy requires accurate dose calculation
      at the dose specification point, at other points in the planning target volume
      (PTV) and in organs at risk. To assess the limitations of treatment planning of
      lung tumours, errors in dose values, calculated by some simple tissue
      inhomogeneity correction algorithms available in a number of currently applied
      treatment planning systems, have been quantified. MATERIALS AND METHODS: Single
      multileaf collimator-shaped photon beams of 6, 8, 15 and 18 MV nominal energy
      were used to irradiate a 50 mm diameter spherical solid tumour, simulated by
      polystyrene, which was located centrally inside lung tissue, simulated by cork.
      The planned dose distribution was made conformal to the PTV, which was a 15 mm
      three-dimensional expansion of the tumour. Values of both the absolute dose at
      the International Commission on Radiation Units and Measurement (ICRU) reference
      point and relative dose distributions inside the PTV and in the lung were
      calculated using three inhomogeneity correction algorithms. The algorithms
      investigated in this study are the pencil beam algorithm with one-dimensional
      corrections, the modified Batho algorithm and the equivalent path length
      algorithm. The calculated data were compared with measurements for a simple beam
      set-up using radiographic film and ionization chambers. RESULTS: For this
      specific configuration, deviations of up to 3.5% between calculated and measured
      values of the dose at the ICRU reference point were found. Discrepancies between
      measured and calculated beam fringe values (distance between the 50 and 90%
      isodose lines) of up to 14 mm have been observed. The differences in beam fringe
      and penumbra width (20-80%) increase with increasing beam energy. Our results
      demonstrate that an underdosage of the PTV up to 20% may occur if calculated dose
      values are used for treatment planning. The three algorithms predict a
      considerably higher dose in the lung, both along the central beam axis and in the
      lateral direction, compared with the actual delivered dose values. CONCLUSIONS:
      The dose at the ICRU reference point of such a tumour in lung geometry is
      calculated with acceptable accuracy. Differences between calculated and measured
      dose distributions are primarily due to changes in electron transport in the
      lung, which are not adequately taken into account by the simple tissue
      inhomogeneity correction algorithms investigated in this study. Particularly for
      high photon beam energies, clinically unacceptable errors will be introduced in
      the choice of field sizes employed for conformal treatments, leading to
      underdosage of the PTV. In addition, the dose to the lung will be wrongly
      predicted which may influence the choice of the prescribed dose level in dose
      escalation studies.

PMID- 11514008
TI  - Radiation-induced myelopathy in long-term surviving metastatic spinal cord
      compression patients after hypofractionated radiotherapy: a clinical and magnetic
      resonance imaging analysis.
AB  - BACKGROUND AND PURPOSE: Hypofractionated radiotherapy is often administered in
      metastatic spinal cord compression (MSCC), but no studies have been published on
      the incidence of radiation-induced myelopathy (RIM) in long-term surviving
      patients. Our report addresses this topic. PATIENTS AND METHODS: Of 465
      consecutive MSCC patients submitted to radiotherapy between 1988 and 1997, 13
      live patients (seven females, six males, median age 69 years, median follow-up 69
      months) surviving for 2 years or more were retrospectively reviewed to evaluate
      RIM. All patients underwent radiotherapy. Eight patients underwent a short-course
      regimen of 8 Gy, with 7 days rest, and then another 8 Gy. Five patients underwent
      a split-course regimen of 5 Gy x 3, 4 days rest, and then 3 Gy x 5. Only one
      patient also underwent laminectomy. Full neurological examination and magnetic
      resonance imaging (MRI) were performed. RESULTS: Of 12 patients submitted to
      radiotherapy alone, 11 were ambulant (eight without support and three with
      support) with good bladder function. In nine of these 11 patients, MRI was
      negative; in one case MRI evidenced an in-field relapse 30 months after the end
      of radiotherapy, and in the other, two new MSCC foci outside the irradiated
      spine. In the remaining patient RIM was suspected at 18 months after radiotherapy
      when the patient became paraplegic and cystoplegic, and magnetic resonance images
      evidenced an ischemic injury in the irradiated area. The only patient treated
      with surgery plus postoperative radiotherapy worsened and remained paraparetic.
      Magnetic resonance images showed cord atrophy at the surgical level, explained as
      an ischemic necrosis due to surgery injury. CONCLUSIONS: On the grounds of our
      data regarding RIM in long-term surviving MSCC patients, we believe that a
      hypofractionated radiotherapy regimen can be used for the majority of patients.
      For a minority of patients, more protracted radiation regimens could be
      considered.

PMID- 11514011
TI  - A survey of radiotherapy quality control practice in the United Kingdom for the
      START trial.
AB  - BACKGROUND AND PURPOSE: This paper compares the quality control checks performed
      in departments in the United Kingdom with those recommended by the Institute of
      Physics and Engineering in Medicine (IPEM) in Report 81. METHOD: The data were
      gathered by the quality assurance team for the START trial, during visits to
      individual departments. Data are compared with the frequencies suggested in IPEM
      report 81. Where applicable, data are also analyzed with respect to machine
      manufacturer. RESULTS: All departments with linear accelerators check the output
      at least weekly for both photons and electrons, however 11% of departments do not
      perform a constancy check of the output on a daily basis. The majority of
      departments check flatness at gantry zero on a monthly basis. However 27% of
      departments never check at non-zero gantry angles. In 51% of departments no
      fluoroscopy checks are performed on simulators on a daily basis. CONCLUSION: The
      majority of departments are following the frequencies suggested in IPEM report 81
      although there are a number of discrepancies particularly for simulators.
      Accelerator type needs to be considered when designing quality assurance checks.
      In many departments more time than is currently allocated is needed on equipment,
      particularly simulators, to complete all of the checks suggested in Report 81.

PMID- 11514012
TI  - Formalisms for MU calculations, ESTRO booklet 3 versus NCS report 12.
AB  - Although the relevance and importance of quality assurance and quality control in
      radiotherapy is generally accepted, only recently, methods for monitor unit (MU)
      calculation and verification have been addressed in recognized recommendations,
      published by the European Society of Therapeutic Radiation Oncology (ESTRO) and
      by the Netherlands Commission on Radiation Dosimetry (Dutreix A, Bjarngard BE,
      Bridier A, Mijnheer B, Shaw JE, Svensson H. Monitor unit calculation for high
      energy photon beams. Physics for clinical radiotherapy. ESTRO Booklet No. 3.
      Leuven: Garant, 1997; Netherlands Commission on Radiation Dosimetry (NCS).
      Determination and use of scatter correction factors of megavoltage photon beams.
      NCS report 12. Deift: NCS, 1998). Both documents are based on the same
      principles: (i) the separation of the output factor into a head and a volume (or
      phantom) scatter component; (ii) the use of a so-called mini-phantom to measure
      and verify the head scatter component; and (iii) the recommendation to use a
      single reference depth of 10 cm for all photon beam qualities. However, there are
      substantial differences between the approach developed in the IAEA-ESTRO task
      group and the NCS approach for MU calculations, which might lead to confusion
      and/or misinterpretation if both reports are used simultaneously or if data from
      the NCS report is applied in the algorithms of the ESTRO report without careful
      consideration. The aim of the present paper is to discuss and to clearly point
      out these differences (e.g. field size definitions, phantom scatter parameters,
      etc.). Additionally, corresponding quantities in the two reports are related
      where possible and several aspects concerning the use of a mini-phantom (e.g.
      size, detector position, composition) are addressed.

PMID- 11514013
TI  - Validation of treatment planning system data: variation in the modelling of three
      6 MV beams for extreme rectangular fields.
AB  - The validation of photon beam data on the Helax-TMS treatment planning system at
      the Northern Centre for Cancer Treatment takes the form of profile and depth dose
      comparisons against measured data for square fields. With a view to using Helax
      TMS to plan fixed source-to-surface distance spine fields, validation of extreme
      rectangular fields was undertaken, based on guidelines published by the American
      Association of Physicists in Medicine Radiation Therapy Committee (Task Group
      report 53). The accuracy with which the Helax-TMS-generated profiles matched
      those measured varied between treatment machines. For three 6 MV beams in the
      department, two beams showed agreement to within 2% in the central portion of the
      field, while the third beam demonstrated differences of up to 4.4% in this
      region. The disparities were attributed to the modelling of the primary dose for
      each beam by Helax-TMS.

PMID- 11514015
TI  - Helospectin, induces a potent relaxation of human airways in vitro.
AB  - Helospectin is a neuropeptide of the vasoactive intestinal
      polypeptide/secretin/glucagon family. Several members of this family display
      biological activities relevant to obstructive airway disease and although the
      literature in this area is rapidly expanding very little is known about the
      effects of helospectin. The smooth muscle relaxation induced by helospectin on
      human bronchi and pulmonary arteries were therefore assessed in vitro, using
      tissue baths. Helospectin induced a potent relaxation of human bronchi and since
      helospectin-like immunoreactive nerve fibers along with possible target receptors
      previously have been reported in the human lung, helospectin might play a role in
      endogenous regulation of airway tone.

PMID- 11514016
TI  - Proline residue 280 in the second extracellular loop (EC2) of the VPAC2 receptor
      is essential for the receptor structure.
AB  - Inspection of the amino acid sequence of the human VPAC1 and the VPAC2 receptors
      after alignment of the conserved residues indicates that the second extracellular
      loop (EC2) is one amino acid shorter in the VPAC1 receptor due to the lack of a
      proline residue in position 294. We hypothesized that this could be of importance
      for receptor structure and/or for ligand recognition. Insertion by directed
      mutagenesis of a proline in that position (<Pro>294 VPAC1) had little consequence
      on the binding of several agonists but reduced the affinity for the VPAC1
      antagonist. Coupling of the <Pro>294 VPAC1 receptor to adenylate cyclase was
      improved, as demonstrated by an increased affinity for VIP and other agonists,
      and by a shift of the VPAC1 antagonist to partial agonist behavior. Deletion of
      the proline 280 (DeltaPro280 VPAC2) in the VPAC2 receptor markedly reduced the
      apparent affinity for all the agonists tested. Replacement of the proline by a
      glycine residue had a smaller effect on the ligands affinities. The proline
      residue in the VPAC2 receptor EC2 is thus essential for the receptor structure,
      and the EC2 domain is involved in ligand recognition and receptor functionality.

PMID- 11514017
TI  - Distribution and daily variations of PACAP in the chicken brain.
AB  - Levels of PACAP38 were measured in different areas of the chicken brain under
      various lighting conditions by radioimmunoassay (RIA). Selected groups of animals
      were maintained under light for 14 h alternating with 10 h of darkness (LD),
      reversed lighting conditions (DL) and constant light (LL) or constant dark (DD).
      Daily variations of PACAP levels were observed in the brainstem, diencephalon,
      telencephalon and retina. In the brainstem and diencephalon, levels of PACAP
      increased during subjective nighttime, except in the DL group where levels were
      elevated between 15-21 h. In the telencephalon, the lowest level of PACAP was
      measured between 12-21 h except in the DL group where two peaks occurred at 18
      and 03 h. In the retina, all 4 groups showed a similar level and pattern, with
      lowest levels during midday hours. No daily variation was observed in the pineal
      gland. According to the present observations, it is suggested that PACAP levels
      differ in several areas of the chicken brain under various lighting conditions
      and photic stimuli do not appear to be the main regulators of the circadian
      variations of PACAP.

PMID- 11514018
TI  - Pyrokinin/PBAN radio-receptor assay: development and application for the
      characterization of a putative receptor from the pheromone gland of Heliothis
      peltigera.
AB  - A radio-receptor assay (RRA) for the insect pyrokinin/PBAN family has been
      developed. The development involved examination of the ligand (3H-tyrosyl-PBAN28
      33NH2)-receptor interaction under various incubation conditions and variations on
      sex pheromone gland membrane preparation. Application of the RRA for a partial
      characterization of the putative pyrokinin/PBAN receptor in the pheromone gland
      of H. peltigera revealed age-dependence of its expression. Pharmacological
      characterization revealed a high correlation between the binding-affinity to the
      receptor of various PBAN-derived peptides and their in vivo pheromonotropic
      bioactivity, and shed light on the interaction of backbone cyclic and linear
      ([Arg27,D-Phe30]PBAN28-33NH2) PBAN antagonists with the receptor.

PMID- 11514019
TI  - Characterization of a novel Sepia officinalis neuropeptide using MALDI-TOF MS and
      post-source decay analysis.
AB  - A novel neuropeptide acting as a myosuppressor on esophagus, funnel and mantle
      muscular fibers has been isolated from the stellar ganglia of the mollusk
      cephalopod Sepia officinalis by means of HPLC analysis. Fractions were monitored
      using a myotropic bioassay. After three separation steps, MALDI-TOF spectrum
      revealed one main peak at m/z 756.6. The partial N-terminal and C-terminal
      digestions by exopeptidases followed by MALDI-TOF analysis allowed the
      determination of the nature of the two C-terminal and N-terminal amino acids.
      Post Source Decay fragmentation of the molecular ion accurately determined the
      following primary sequence: Val-Tyr-Ser-Ala-Pro-Tyr-Gly-OH. The mapping of this
      heptapeptide performed in ESI-MS revealed that its distribution is restricted to
      the stellar ganglia, the giant fibers III, and the nervous bundle containing the
      giant fibers II and the palleal nerve. The neuropeptide was not detected in the
      hemolymph suggesting a release by nerve endings next to the targets.

PMID- 11514021
TI  - Angiotensin IV enhances LTP in rat dentate gyrus in vivo.
AB  - Angiotensins have been shown to play a significant role in a variety of
      physiological functions including learning and memory processes. Relatively
      recent evidence supports the increasing importance of angiotensin IV (Ang IV), in
      many of these functions previously associated only with Ang II, including
      learning and memory. An interesting hypothesis generated by these results has
      been that Ang II is a precursor for the production of a more active peptide
      fragment, Ang IV. Since Ang II impairs learning and memory, when administered
      directly or released into the hippocampal dentate gyrus, and inhibits long term
      potentiation (LTP) in medial perforant path-dentate granule cell synapses, as
      well; it remained to be seen what effects Ang IV had on LTP in these same
      synapses. Results of this study show clearly that Ang IV significantly enhances
      LTP, and the enhancement is both dose and time dependent. The following solutions
      of Ang IV were administered over a five min period, at the end of baseline and
      before the first tetanus was applied: 2.39, 4.78, and 9.56 nM. An inverted U-type
      dose related effect was observed. A complex time related effect was observed with
      a maximum at 5 min, a return to normal LTP at 30 min and a minimum below normal
      at 90 min, and a return to normal LTP at 120 min. The effects of the 4.78 nM
      solution were determined at the following intervals between administration and
      the first tetanus: 5, 15, 30, 60, 90, and 120 min. The enhancement of LTP can be
      prevented by pretreatment with Divalinal, an Ang IV antagonist, without any
      effect on normal LTP. Two solutions of Divalinal were used; 5 nM and 5 microM,
      and the 5 microM was more effective and completely blocked the enhancement of
      normal LTP. Results were also obtained with 4.78 nM Nle1-Ang IV (Norleucine), an
      Ang IV agonist. Norleucine was less effective than Ang IV in the enhancement of
      normal LTP and displayed a similar time course of activity. Both Ang IV and
      Norleucine produced a significant suppression of normal LTP at 90 min; that
      remains to be explained. However, the inhibition by Ang IV was dose dependent and
      was blocked by Divalinal. The fact that the Ang IV enhancement of normal LTP was
      blocked by losartan, an Ang II AT1 receptor antagonist, is puzzling since
      Divalinal had no effect on the inhibition of LTP by Ang II.

PMID- 11514022
TI  - A central link between angiotensinergic and cholinergic systems; role of
      vasopressin.
AB  - Participation of central cholinergic system in the effects of
      intracerebroventricular (i.c.v.) injection of angiotensin II (Ang II) on blood
      pressure and heart rate was studied in conscious, freely moving rats. Ang II dose
      dependently increased blood pressure and decreased heart rate. Both atropine and
      mecamylamine (i.c.v.) pretreatments prevented the cardiovascular effects of Ang
      II. Pretreatment with a vasopressin V1 antagonist also prevented the
      cardiovascular responses to Ang II. Our data suggest that the central pressor
      effect of Ang II is mediated in part by central acetylcholine via both muscarinic
      and nicotinic receptors, and vasopressin participates in this effect through V1
      receptors.

PMID- 11514020
TI  - Effects of two novel non-peptide antagonists at the rabbit bradykinin B2
      receptor.
AB  - Large species differences have been previously observed in the pharmacology of
      bradykinin (BK) B2 receptor antagonists. We investigated the effect of two novel
      non-peptide antagonists, compound 9 (a benzodiazepine peptidomimetic related to
      icatibant) and the thiosemicarbazide bradyzide on the rabbit B2 receptor
      (contractility of the jugular vein, competition of [3H]BK binding to a B2
      receptor-green fluorescent protein (B2R-GFP) conjugate, subcellular distribution
      of B2R-GFP). While compound 9 is about 9000-fold less potent than icatibant, it
      shares with the latter peptide drug a selective, insurmountable and largely
      irreversible antagonist behavior against BK and the capacity to translocate B2R
      GFP from the membrane into the cells. Bradyzide, reportedly very potent at rodent
      B2 receptors, was a competitive and reversible antagonist of moderate potency at
      the rabbit B2 receptor (contractility pA2 6.84, binding competition IC50 5 nM).
      The C-terminal region of icatibant, reproduced by compound 9, is likely to be
      important in the non-equilibrium behavior of icatibant. Bradyzide, a non-peptide
      antagonist developed on different structural grounds, is competitive at the
      rabbit B2 receptor.

PMID- 11514024
TI  - Analysis of responses to hAmylin, hCGRP, and hADM in isolated resistance arteries
      from the mesenteric vascular bed of the rat.
AB  - Responses to human calcitonin gene-related peptide (hCGRP) and human
      adrenomedullin (hADM) hAmylin were investigated in isolated mesenteric resistance
      arteries from the rat. The results of the present investigation show that hCGRP,
      hAmylin, and hADM induce dose-related vasodilator responses in isolated
      resistance arteries from the rat mesenteric vascular bed. Vasodilator responses
      to hCGRP and hAmylin were not altered after denuding the vascular endothelium,
      after administration of the nitric oxide synthase inhibitor L-NA, or after
      administration of the soluble guanylate cyclase inhibitor ODQ, suggesting that
      vasodilator responses to hCGRP and hAmylin are not mediated by the release of
      nitric oxide from the vascular endothelium and the subsequent increase in cGMP.
      Vasodilator responses to hCGRP, hAmylin, and hADM were not altered by the
      vascular selective K+(ATP) channel antagonist U-37883A. The role of the CGRP1
      receptor was investigated and responses to hCGRP and hAmylin, but not hADM, were
      significantly reduced following administration of hCGRP-(8-37). Moreover,
      vasodilator responses to hCGRP and hAmylin, but not hADM, were significantly
      reduced by hAmylin-(8-37), suggesting that an hAmylin-(8-37)-sensitive receptor
      mediates responses to hCGRP and hAmylin in the rat mesenteric artery. These data
      suggest that hCGRP and hAmylin have direct vasodilator effects in the isolated
      mesenteric resistance artery that are mediated by hAmylin-(8-37)- and hCGRP-(8
      37)-sensitive receptors.

PMID- 11514023
TI  - Histamine release induced by dendroaspis natriuretic peptide from rat mast cells.
AB  - Dendroaspis natriuretic peptide (DNP), recently isolated from the venom of the
      green Mamba snake Dendroaspis angusticeps, is a 38 amino acid peptide containing
      a 17 amino acid disulfide ring structure similar to that of the natriuretic
      peptide family. The natriuretic peptide family is known to induce histamine
      release from human and rat mast cells, but there are no published data concerning
      the effects of DNP on histamine release from mast cells. The purpose of this
      study is to investigate whether DNP induces the histamine release from rat
      peritoneal mast cells (RMPCs) and to determine the mechanism of DNP-induced
      histamine release from RPMCs. After treatment of RPMC with DNP, mast cell
      degranulation was observed, and calcium uptake and histamine release were
      measured. DNP released the histamine, induced the mast cell degranulation, and
      increased the calcium uptake of RPMCs, in a dose-dependent manner. The results
      indicate that DNP can increase Ca-uptake and induce histamine release.

PMID- 11514025
TI  - Cloning of a calcitonin gene-related peptide from genomic DNA and its mRNA
      expression in flounder, Paralichthys olivaceus.
AB  - A part of genomic DNA including the calcitonin gene-related peptide (CGRP) gene
      was cloned from flounder by the genome-walking method. The intron/exon boundary
      was predicted to occur exactly at the same position as in salmon. The 37-amino
      acid molecule coded by the region from the intron/exon boundary to the stop codon
      was preceded by a typical Lys-Arg cleavage signal and included a
      cleavage/amidation site common to the CGRP of other vertebrates. The predicted
      amino acid sequence of flounder CGRP had 78%, 78%, 78%, 81%, and 73-78% identity
      to that of salmon, cod, frog, chicken, and mammalian CGRPs, respectively. Among
      vertebrates, CGRP is more conserved than calcitonin (CT) because the identity of
      flounder CT to mammalian CTs is 31-50%. Expression analysis indicated that this
      hormone is synthesized in the brain, heart, intestine, testis, and ovary. Since
      we have previously shown that the CGRP receptor is expressed in these tissues, it
      is suggested that CGRP secreted from each tissue functions in a paracrine or
      autocrine manner.

PMID- 11514031
TI  - Structure-activity relationships of neuropeptide FF: role of C-terminal regions.
AB  - A structure-activity study was carried out to determine the importance of the C
      terminal amino acids of the octapeptide Neuropeptide FF (NPFF) in binding and
      agonistic activity. Affinities of NPFF analogues were tested toward NPFF
      receptors of the rat spinal cord and the human NPFF2 receptors transfected in CHO
      cells. The activities of these analogues were evaluated by their ability to both
      inhibit adenylate cyclase in NPFF2 receptor transfected CHO cells and to reverse
      the effect of nociceptin on acutely dissociated rat dorsal raphe neurons. The
      substitutions of Phenylalanine8 by a tyrosine, phenylglycine or homophenylalanine
      were deleterious for high affinity. Similarly, the replacement of Arginine7 by a
      lysine or D. Arginine induces a loss in affinity. The pharmacological
      characterization showed that the presence of the amidated Phe8 and Arg7 residues
      are also extremely critical for activation of anti-opioid effects on dorsal raphe
      neurons. The sequence of the C-terminal dipeptide seems also to be responsible
      for the high affinity and the activity on human NPFF2 receptors. The results
      support the view that a code messaging the molecular interaction toward NPFF
      receptors is expressed in the C-terminal region of these peptides but the N
      terminal segment is important to gain very high affinity.

PMID- 11514032
TI  - Oxytocin decreases carrageenan induced inflammation in rats.
AB  - The effects of oxytocin on carrageenan-induced inflammation in rat hindpaw was
      examined. Oxytocin at 100 (P < 0.05) and 1000 microg/kg s.c. (P < 0.05), but not
      at 1 and 10 microg/kg s.c., reduced the edema of the paw when measured up to 10 h
      after the injection. An additional experiment showed that the effect was
      comparable to the effect of the glucocorticoid dexamethasone. No effect was found
      by oxytocin i.c.v. In addition, rats with carrageenan-induced inflammation given
      oxytocin (1000 microg/kg s.c.) responded differently to nociceptive mechanical
      stimulation (P < 0.05) and had a reduced amount of myeloperoxidase (marker for
      neutrophil recruitment) in the paw (P < 0.01).

PMID- 11514027
TI  - Place aversion induced by microinjections of C-fragment of substance P into the
      dorsal periaqueductal gray of rats is mediated by tachykinin NK1 receptors.
AB  - Neural circuits in the dorsal periaqueductal gray matter (dPAG) play an important
      role in the integration of defensive behavior. The neurokinin substance P causes
      conditioned place aversion when administered into this region. The present study
      examined whether these effects may be mimicked by its carboxy-terminal amino acid
      sequence and whether they are influenced by prior treatment with the tachykinin
      NK1 receptor antagonist WIN51,708. The behavioral testing apparatus is a circular
      open field consisting of 4 uniform quadrants that are equally preferred by the
      rats prior to drug treatments. For conditioning, rats received drug injections on
      three consecutive days and were placed into their assigned quadrant. The carboxy
      terminal analog (17.5 pmol/0.2 microl) applied into the dPAG produced place
      aversion effects with reduced time spent in the drug-paired quadrant on the
      testing day. The effects of the carboxy-terminal analog was antagonized by
      pretreatment with WIN51,708 (20 mg/kg, i.p.). Microinjection of WIN51,708 (20
      mg/kg, i.p.), by its own, did not produce significant effects. These findings
      suggest that previous reports showing conditioned place aversion effects of SP
      injected into the dPAG are encoded by its carboxy-terminal sequence and due to
      its action on tachykinin NK1 receptors.

PMID- 11514026
TI  - The capsaicin VR1 receptor mediates substance P release in toxin A-induced
      enteritis in rats.
AB  - The mechanism by which Clostridium difficile toxin A causes substance P (SP)
      release and subsequent inflammation in the rat ileum is unknown. Pretreatment
      with the vanilloid receptor subtype 1 (VR1) antagonist, capsazepine, before toxin
      A administration significantly inhibited toxin A-induced SP release and
      intestinal inflammation. Intraluminal administration of the VR1 agonist capsaicin
      caused intestinal inflammation similar to the effects of toxin A. Pretreatment
      with capsazepine before capsaicin administration also significantly inhibited
      capsaicin-induced intestinal inflammation. These results suggest that
      intraluminal toxin A causes SP release from primary sensory neurons via
      stimulation of VR1 receptors resulting in intestinal inflammation.

PMID- 11514030
TI  - Beta-endorphin- and GABA-mediated depressor effect of specific electroacupuncture
      surpasses pressor response of emotional circuit.
AB  - It has been proved that input of specific electroacupuncture (EA) can activate
      beta-endorphin(beta-EP)ergic and noradrenergic neurons projecting to the rostral
      ventrolateral medulla (RVL), the latter acting upon the RVL-GABAergic
      interneurons, thereby produce depressor effect. The present study further shows
      that: (1) The EA depressor effect is strong enough to surpass the pressor
      response of the AC (nucleus amygdaloideus centralis)-emotional circuit, (2) both
      beta-endorphin (beta-EP) and GABA in the RVL mediate the EA antagonistic effect,
      (3) the EA effect does not take place in the AC and paraventricular nucleus (two
      key nuclei besides the RVL, which also have beta-EPergic input) in the emotional
      circuit.

PMID- 11514029
TI  - Behavioral and neuroendocrine actions of endomorphin-2.
AB  - The effects of intracerebroventricularly administered endomorphin-2 (EM2) on open
      field activity and the hypothalamo-pituitary-adrenal (HPA) system were
      investigated. EM2 (0.25-1 microg) significantly increased both the locomotor and
      the rearing activity, resulting in a bell-shaped dose-response curve. EM2 also
      enhanced corticosterone release, with an even more profound downturn phase at
      higher concentrations. The corticotropin-releasing hormone (CRH) antagonist alpha
      helical CRH9-41 completely abolished the EM2-evoked endocrine and behavioral
      responses. These findings reinforce the hypothesis that the endomorphins may play
      a significant role in the regulation of locomotion, rearing activity and the HPA
      system through the release of CRH.

PMID- 11514034
TI  - Evidence that the chromogranin B fragment 368-417 extracted from a
      pheochromocytoma is phosphorylated.
AB  - A rabbit antiserum was raised against a synthetic peptide corresponding to
      residues 403 to 417 of human chromogranin B. This peptide was chosen to match the
      potential C-terminal end of a putative proteolytic fragment of the protein
      located between dibasic doublets in positions 366-367 and in positions 418-419 of
      the precursor. A radioimmunoassay based on this antiserum was developed and used
      to detect the protein or a fragment thereof in a pheochromocytoma tumor extract.
      One fragment was purified to homogeneity by successive reverse-phase HPLC
      chromatographies. The N-terminal sequence established by automated Edman
      degradation, was N-Y-P-S-L-E-L-D-K-M-A-H-G-Y-G-E-E-S-E-E-E-R corresponding to the
      368-389 sequence of human chromogranin B. Taking into account the specificity of
      the antiserum used for peptide identification and alignment with the precursor
      sequence, we deduced that the purified peptide was chromogranin B (368-417) and
      represented a new peptide generated by limited proteolysis of chromogranin B.
      Combining electrospray mass-spectrometry and enzymatic dephosphorylation, we
      demonstrated that this peptide was phosphorylated.

PMID- 11514033
TI  - Adrenomedullin expression in pathogen-challenged oral epithelial cells.
AB  - Adrenomedullin, a multifunctional peptide, is expressed by many surface
      epithelial cells and, previously, we have demonstrated that adrenomedullin has
      antimicrobial activity. The oral cavity contains an epithelium that is
      permanently colonized by microflora, yet infections in a host are rare. We
      exposed oral keratinocytes to whole, live cells from four microorganisms commonly
      isolated from the oral cavity, Porphyromonas gingivalis, Streptococcus mutans,
      Candida albicans and Eikenella corrodens. There was upregulation of protein and
      gene expression in these cells in response to bacterial suspensions, but not with
      the yeast, Candida albicans. We propose there is a potential role for microbial
      products in enhancing mucosal defense mechanisms and that adrenomedullin
      participates in the prevention of local infection, thus contributing to host
      defense mechanisms.

PMID- 11514036
TI  - Human fibrinopeptide A mediates allergic reaction in mice in the acute phase.
AB  - We detected a human humoral peptide that deglycosylates mouse antibody IgE, and
      found that this peptide had the amino acid sequence ADSGEGDFLAEGGGV. The peptide
      synthesized according to the sequence also deglycosylated the antibody IgE. The
      deglycosylated IgE did not induce mouse systemic anaphylaxis. Human
      fibrinopeptide A has the amino acid sequence indicated above, and a polypeptide
      extracted from human urine showed an antiallergic effect on humans and mice,
      which strongly suggests that fibrinopeptide A mediates allergic reaction via
      antibody IgE-deglycosylation, and is excreted as a polypeptide in urine.

PMID- 11514028
TI  - Substance P and its transglutaminase-synthesized spermine derivative elicit
      yawning behavior via nitric oxide in rats.
AB  - Previously, we showed that intranigrostriatal injection of substance P (SP) cause
      behavioral changes in rats. Those effects, such as locomotion and food intake,
      resulted related to catecholamines release modulated by nitric oxide [18]. Here
      we report that intranigrostriatal injection of SP elicited yawning in rats.
      Moreover, since in previous studies we demonstrated that transglutaminase
      synthesized gamma-(glutamyl5)spermine derivative of SP (Spm-SP) could be a useful
      tool in differentiating NK1 receptors [5,19,26], we reports the effects of
      injecting the selective septide-sensitive NK1 receptor agonist Spm-SP into the
      nigrostriatal region of the rat brain on yawning. The administration of L
      N(omega)-nitroarginine methyl ester, a NO-synthase inhibitor, stereospecifically
      reduced in a dose related manner both SP and Spm-SP-induced yawning. In contrast,
      L-arginine pretreatment prevented the effect of NO-synthase inhibitor. Moreover,
      the NK1 antagonist RP,67580 blocked yawning behavior induced by both SP and Spm
      SP, whereas the pretreatment with systemic reserpine determined its increase. The
      administration of NO-synthase inhibitor resulted ineffective in reducing SP and
      Spm-SP-induced yawns in reserpinized rats. Finally, yawns elicited by SP or Spm
      SP were blocked when rats were treated with scopolamine but not with
      methylscopolamine. These results indicate that yawning induced in rats by SP
      injection is dependent upon endogenous dopamine levels in brain nigrostriatal
      area. Moreover, we demonstrate, by using Spm-SP, that septide-sensitive NK1
      receptor are specifically involved in yawning behavior.

PMID- 11514039
TI  - Sample size determination for equivalence test using rate ratio of sensitivity
      and specificity in paired sample data.
AB  - Before implementing a new diagnostic test, we may wish to study whether this test
      is noninferior to a reference test with respect to the sensitivity and/or the
      specificity. This paper discusses sample size determination for one-sided
      equivalence (or noninferiority) testing of the rate ratio using paired-sample
      data. Using large sample theory, this paper derives asymptotic sample size
      formulae for the required number of subjects giving a desired power 100(1 -
      beta)% at a specified alpha-level. To evaluate the accuracy of these formulae,
      this paper considers several test statistics and uses Monte Carlo simulation to
      estimate the corresponding type I error and power with the given resulting sample
      sizes in a variety of situations. Finally, this paper notes those situations for
      which the asymptotic sample size formulae developed here are of limited use and
      suggests a simple empirical adjustment to alleviate this limitation.

PMID- 11514037
TI  - Clinical trials for drug registrations in Asian-Pacific countries: proposal for a
      new paradigm from a statistical perspective.
AB  - The world has become more interdependent in the movement of free trade and global
      markets. The regulations for approval of new drugs in the Asian markets have
      always been an important issue in the free trade negotiation between the U.S.-
      and E.U.-based international manufacturers and the Asian-Pacific countries, since
      pharmaceuticals are of large trade value for them. In 1998 the University of Hong
      Kong and the Singapore National Medical Research Council jointly hosted the first
      Asian Clinical Trials Conference. The Society for Clinical Trials was invited as
      a collaborator for the event, which signified a milestone for interaction between
      the East and West in the discussion of clinical trials. Many have participated in
      the discussion of drug approval and registration issues for the Asian region
      based on the drug development experience in the United States. However, there are
      many interesting differences between the two regions, which lead to different
      approval processes for new drugs developed by the U.S.- and E.U.-based
      international manufacturers. This article highlights some regulatory dilemmas and
      some key statistical concepts pertinent to these differences. The purpose of this
      paper is to resolve the regional regulatory and scientific dilemma. A new
      paradigm of sample size design and data analysis for drug approval for countries
      in the Asian-Pacific region is proposed. The central premise is that substantial
      information from multicenter studies has already shown efficacy in the United
      States or the European Union when a drug manufacturer seeks marketing approval in
      an Asian country. This leads to the idea of a "consistency trial" using the
      method of Bayesian most plausible prediction. The method is illustrated with an
      example.

PMID- 11514041
TI  - The inhaled Steroid Treatment as Regular Therapy in early asthma (START) study:
      rationale and design.
AB  - Although the beneficial effects of treatment with inhaled steroids in asthma are
      widely accepted, the role of early intervention in patients with mild asthma
      remains unsettled. Conventional efficacy trials are often of short duration and
      involve highly selected patient populations that exclude many patients typical of
      those encountered in routine clinical practice. Hence, a large "real-world"
      effectiveness study is needed to evaluate the benefits of early intervention with
      inhaled steroids in patients with mild, persistent asthma. In the START (inhaled
      Steroid Treatment As Regular Therapy in early asthma) study, patients ages 6-60
      years, from 31 countries and districts worldwide with mild persistent asthma,
      have been randomized to once-daily treatment with budesonide, 200 microg (for
      patients < 11 years) or 400 microg (for patients > or = 11 years), or placebo via
      Turbuhaler for 3 years. The double-blind treatment period will be followed by a 2
      year period of open budesonide treatment. Throughout the study, other asthma
      medication including glucocorticosteroids can be given as judged appropriate by
      the investigator. Lung function will be measured by spirometry using standardized
      techniques at 3-month intervals throughout the study, and bronchodilator
      reversibility will be measured annually. The primary outcome measures are the
      time to the first severe asthma-related event during the first 3 years of the
      study and the change in postbronchodilator forced expiratory volume in 1 second
      (FEV(1)) from baseline during the entire 5-year study period. These measures have
      been chosen to reflect the progression of mild asthma toward more severe asthma
      and the extent of irreversible airflow limitation, which should reflect the
      degree of airway remodeling.

PMID- 11514040
TI  - Uniform power method for sample size calculation in historical control studies
      with binary response.
AB  - Makuch and Simon gave a sample size calculation formula for historical control
      (HC) studies that assumed that the observed response rate in the control group is
      the true response rate. We dropped this assumption and computed the expected
      power and expected sample size to evaluate the performance of the procedure under
      the omniscient model. When there is uncertainty in the HC response rate but this
      uncertainty is not considered, Makuch and Simon's method produces a sample size
      that gives a considerably lower power than that specified. Even the larger sample
      size obtained from the randomized design formula and applied to the HC setting
      does not guarantee the advertised power in the HC setting. We developed a new
      uniform power method to search for the sample size required for the experimental
      group to yield an exact power without relying on the estimated HC response rate
      being perfectly correct. The new method produces the correct uniform predictive
      power for all permissible response rates. The resulting sample size is closer to
      the sample size needed for the randomized design than Makuch and Simon's method,
      especially when there is a small difference in response rates or a limited sample
      size in the HC group. HC design may be a viable option in clinical trials when
      the patient selection bias and the outcome evaluation bias can be minimized.
      However, the common perception of the extra sample size savings is largely
      unjustified without the strong assumption that the observed HC response rate is
      equal to the true control response rate. Generally speaking, results from HC
      studies need to be confirmed by studies with concurrent controls and cannot be
      used for making definitive decisions.

PMID- 11514038
TI  - Graphical search for two-stage designs for phase II clinical trials.
AB  - In a typical two-stage design employed in a phase II cancer clinical trial for
      efficacy screening, a fixed number of patients are initially enrolled. The trial
      may be terminated for lack of clinical efficacy of treatment if the observed
      number of treatment successes after the first stage is too small. Otherwise, an
      additional fixed number of patients are enrolled to accumulate additional
      information on efficacy. Simon's optimal design and minimax design have often
      been applied to designing phase II clinical trials. Other designs have largely
      been ignored. In this paper, we introduce a graphical method to search for a good
      design that is a compromise between the optimal and the minimax designs.

PMID- 11514035
TI  - Central galanin and N-terminal galanin fragment induce c-Fos immunoreactivity in
      the medulla oblongata of the anesthetized rat.
AB  - This immunohistochemical study analyzed the c-Fos expression (c-Fos-ir) induced
      by galanin injections. Galanin and N-terminal galanin fragment (1-15) induced a
      significant increase of c-Fos expression (c-ir) within the medulla oblongata 90
      min and 6 h. after intracisternal injections. This expression has been studied
      mainly in the nucleus of the solitary tract and in the ventrolateral medulla
      showing different temporal profiles for both peptides. The presence of c-Fos-ir
      in TH-positive cells was analyzed in all the groups. These results may be
      relevant to understand the role of galanin in several functions including central
      cardiovascular control.

PMID- 11514042
TI  - Design and analytic considerations in determining the cost-effectiveness of early
      intervention in asthma from a multinational clinical trial.
AB  - Demand for economic and outcomes data in support of drug formulary listing in
      private and government-sponsored health programs has led to fundamental changes
      in drug development. In part as a response to these pressures, the pharmaceutical
      industry has begun to include economic and quality-of-life endpoints in clinical
      trials with the hope of providing information to answer health policy questions
      on the economic value of its products. Here, the design and health economic
      techniques that will be used to analyze the START (inhaled Steroid Treatment As
      Regular Therapy in early asthma) study-a multinational (31 countries),
      randomized, placebo-controlled trial of 7240 patients with mild asthma over 3
      years-will be presented. START compares the effect of once-daily administration
      of an inhaled glucocorticosteroid (Pulmicort Turbuhaler to conventional therapy
      in the management of newly diagnosed asthma, for which the use of this therapy is
      currently not the standard. The START study will examine both clinical
      effectiveness (measured as symptom-free days) and asthma-related costs for both
      treatment arms, aggregated for all patients across all countries. We believe that
      presenting the analytical plan prior to disseminating the results is an important
      way of increasing the credibility of economic evaluations. However, using
      clinical trials for collecting economic data poses several challenges, and the
      methods for conducting such evaluations are being developed. This paper will
      present and discuss several methodological options and the current state of the
      art for conducting economic evaluations alongside multinational clinical trials.

PMID- 11514049
TI  - Expression and action of transforming growth factor beta (TGFbeta1, TGFbeta2,
      TGFbeta3) in normal bovine ovarian surface epithelium and implications for human
      ovarian cancer.
AB  - The majority of ovarian tumors are derived from the single layer of epithelial
      cells on the surface of the ovary termed the ovarian surface epithelium (OSE).
      Stromal cell-OSE interactions are postulated to be an important aspect of normal
      OSE biology and the biology of ovarian cancer. Transforming growth factor beta
      (TGFbeta) has been shown to often be a mesenchymal cell-derived growth factor
      that mediates stromal cell-epithelial cell interactions in a variety of different
      tissues. The current study investigates the expression and action of TGFbeta
      isoforms (TGFbeta1, TGFbeta2, and TGFbeta3) in OSE and the underlying stroma in
      both normal bovine and human tumor tissues. Normal bovine ovaries are similar to
      human ovaries and are used as a model system to investigate normal OSE and
      stromal cell functions. All three TGFbeta isoforms and their receptor,
      transforming growth factor beta receptor type II (TGFbetaRII), proteins were
      found to be detected in the OSE from normal bovine ovaries using
      immunohistochemistry. Ovarian stromal tissue also contained positive
      immunostaining for TGFbeta isoforms and TGFbetaRII. RNA was collected from normal
      bovine OSE and ovarian stromal cells to examine TGFbeta gene expression.
      TGFbeta1, TGFbeta2, and TGFbeta3 transcripts were detected in both freshly
      isolated and cultured bovine OSE and stromal cells by a sensitive quantitative
      polymerase chain reaction assay. TGFbeta1 and TGFbeta2 mRNA levels were found to
      be present at similar levels in freshly isolated OSE and stroma. Interestingly,
      TGFbeta3 mRNA levels were significantly higher in freshly isolated OSE than
      stromal cells. All but TGFbeta3 mRNA in OSE increased when the cells were
      cultured. Observations indicate that normal bovine OSE and stroma cells express
      the three TGFbeta isoforms in vivo and in vitro. Human ovarian tumors from stage
      II, stage III and stage IV cases were found to express TGFbeta1, TGFbeta2,
      TGFbeta3 and TGFbetaRII protein primarily in the epithelial cell component by
      immunohistochemistry analysis. The stromal cell component of the human ovarian
      tumors contained little or no TGFbeta or TGFbetaRII immunostaining. TGFbeta
      actions on bovine OSE and stromal cells were also investigated. TGFbeta was found
      to inhibit the growth of OSE, but not stromal cells. To further examine the
      actions of TGFbeta on OSE, the expression of two growth factors previously shown
      to be expressed by OSE were analyzed. TGFbeta1 was found to stimulate the
      expression of both keratinocyte growth factor (KGF) and kit ligand/stem cell
      factor (KL) by bovine OSE. Therefore, TGFbeta actions on OSE will likely promote
      a cascade of cell-cell interactions and cellular responses involving multiple
      growth factors. The effects of regulatory agents on TGFbeta expression by the
      bovine OSE were examined. Transforming growth factor alpha (TGFalpha) stimulated
      TGFbeta1 expression, TGFbeta1 stimulated TGFbeta2 expression, and follicle
      stimulating hormone (FSH) stimulated TGFbeta3 expression. These results
      demonstrate that TGFbeta isoforms are regulated differently by the regulatory
      agents tested. In summary, all the TGFbeta isoforms are differentially expressed
      by the OSE and TGFbeta appears to have an important role in regulating OSE and
      possibly stromal-OSE interactions. A complex network of endocrine and paracrine
      interactions appears to influence the expression and actions of TGFbeta on OSE.
      Abnormal expression and/or action of TGFbeta is postulated to in part be involved
      in the onset and progression of ovarian cancer.

PMID- 11514044
TI  - ACTIVE: a cognitive intervention trial to promote independence in older adults.
AB  - The Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) trial
      is a randomized, controlled, single-masked trial designed to determine whether
      cognitive training interventions (memory, reasoning, and speed of information
      processing), which have previously been found to be successful at improving
      mental abilities under laboratory or small-scale field conditions, can affect
      cognitively based measures of daily functioning. Enrollment began during 1998; 2
      year follow-up will be completed by January 2002. Primary outcomes focus on
      measures of cognitively demanding everyday functioning, including financial
      management, food preparation, medication use, and driving. Secondary outcomes
      include health-related quality of life, mobility, and health-service utilization.
      Trial participants (n = 2832) are aged 65 and over, and at entry into the trial,
      did not have significant cognitive, physical, or functional decline. Because of
      its size and the carefully developed rigor, ACTIVE may serve as a guide for
      future behavioral medicine trials of this nature.

PMID- 11514052
TI  - Endocrine regulation of testicular function in men: implications for
      contraceptive development.
AB  - The testicle has two important and complimentary functions in the adult male: the
      production of sperm and the synthesis of testosterone. Testicular function is
      directed by the central nervous system through its effects on the pituitary
      gland. Precise regulation of testicular function is accomplished by an elegant
      endocrine feedback loop in which the secretion of pituitary gonadotropins is
      stimulated by the pulsatile release of GnRH from the hypothalamus and modulated
      by testicular hormones. Inhibin, testosterone and its metabolites inhibit the
      secretion of the gonadotropins both directly at the pituitary and centrally at
      the level of the hypothalamus. In the testis, LH mainly stimulates testosterone
      production and FSH promotes spermatogenesis, but the exact details of these
      actions are only now being elucidated. The discovery of novel mutations in
      gonadotropin structure and signaling provide unique insight into the roles of
      these crucial hormones in the development and function of the male reproductive
      axis. A key goal of research into hormonal regulation of testicular function is
      the development of reversible, safe and effective male hormonal contraceptives.
      Recent promising trials of hormonal contraceptive combinations may soon bring the
      promise of male contraception to fruition.

PMID- 11514043
TI  - Design of a group-randomized Streptococcus pneumoniae vaccine trial.
AB  - A group-randomized, double-masked, phase III trial of a Streptococcus pneumoniae
      conjugate vaccine is being conducted in American Indian populations in the
      southwestern United States. Approximately 9000 infants will be enrolled in the
      primary efficacy cohort with vaccine allocation determined by community of
      residence. The trial is designed to continue until 48 cases of invasive
      pneumococcal disease due to vaccine serotypes have accumulated. Thirty-eight
      geographically and socially distinct areas were randomized within blocks formed
      by population size and geographic location. This design affords the opportunity
      to capture the effects of herd immunity (indirect effects) by estimating the
      impact of the vaccine intervention on nonimmunized infants. Group-randomized
      trials have challenging design and analysis features, many of which are discussed
      here in the context of the first such trial designed to lead to licensure of a
      drug or biologic in the United States.

PMID- 11514053
TI  - Androgens induce expression of SPAK, a STE20/SPS1-related kinase, in LNCaP human
      prostate cancer cells.
AB  - Genes that are regulated by androgens in the human prostate are believed to play
      an essential role in prostate physiology and they may also be involved in the
      proliferative response of prostate cancer cells to androgens. We used a cDNA
      subtraction approach to identify novel androgen-regulated transcripts in LNCaP
      cells that were exposed to 0.1 nM R1881 for 24 h. We report here that SPAK, a
      recently identified STE20/SPS1-related kinase that modulates p38 MAP kinase
      activity, exhibited increased expression in androgen-treated LNCaP cells.
      Androgen regulation of SPAK was both dose- and time-dependent. R1881-induced SPAK
      expression was completely abrogated by the antiandrogen casodex and by
      actinomycin D indicating that androgen induction of SPAK requires the androgen
      receptor and transcription. Cycloheximide caused a partial inhibition of R1881
      induced SPAK expression which suggests that androgen induction of SPAK expression
      may require synthesis of additional proteins. Northern blot and ribonuclease
      protection assays demonstrated that SPAK is expressed at high levels in normal
      human testes and prostate, as well as in a number of breast and prostate cancer
      cell lines. These results identify SPAK, a member of a key cell signalling
      pathway, as an androgen-responsive gene in LNCaP cells. We hypothesize that SPAK
      may mediate androgen action in the normal and cancerous prostate gland.

PMID- 11514058
TI  - Regulation of telomerase during human placental differentiation: a role for
      TGFbeta1.
AB  - The transient tumor-like attributes of the first-trimester placenta anchor the
      developing embryo to the uterine wall thus establishing a vital link between the
      mother and the fetus. Dysregulation of this invasive behavior and/or controlled
      proliferation of the placenta is associated with abnormal pregnancies. Several of
      these diseased states also exhibit aberrant telomerase activity, among other
      pathophysiological manifestations. Considering the strong correlation between
      telomerase activity and tumorigenesis, it was of interest to see whether the
      crucial processes of trophoblast proliferation and differentiation were brought
      about through the modulation of telomerase. Using two in vitro model systems of
      trophoblast differentiation, we demonstrate here that telomerase activity is
      negatively regulated during placental differentiation. We further show that this
      modulation is at the level of transcription of hTERT. We also propose a role for
      TGF beta1 in regulating telomerase activity in differentiating trophoblasts by
      down-regulating the expression of hTERT at the transcriptional level.

PMID- 11514055
TI  - Identification of the somatostatin receptor subtypes involved in regulation of
      growth hormone secretion in chickens.
AB  - The effects of somatostatin (SRIF) are mediated through five distinct G-protein
      coupled receptors (SSTR1-5). In the present study, pituitary cells from 6-week
      old chickens were subjected to reverse hemolytic plaque assays for growth hormone
      (GH) in the presence of SSTR subtype specific nonpeptidyl agonists. A SSTR2
      selective agonist (L-779,976) potently inhibited both basal and GH-releasing
      hormone (GHRH)-stimulated GH release at low nanomolar concentrations. A SSTR5
      agonist (L-817,818) inhibited GH release only under basal conditions and in a
      subpopulation of somatotrophs. In contrast, a SSTR4 selective agonist (L-803,087)
      used at high nanomolar concentrations modestly stimulated GH release under basal
      conditions but did not influence GHRH-stimulated GH secretion. The SSTR1 and
      SSTR3 specific agonists did not affect GH secretion under any condition tested.
      Reverse transcription-polymerase chain reaction (RT-PCR) and Northern blot
      analysis using a partial cDNA for chicken SSTR2 showed relatively high levels of
      SSTR2 mRNA in the anterior pituitary (both in the caudal and cephalic lobes) and
      brain and detectable levels in liver, muscle, heart and small intestine. These
      results indicate that SSTR2 is the primary mediator of the inhibitory effects of
      SRIF on GH secretion in chickens.

PMID- 11514059
TI  - Fusion estrogen receptor proteins: toward the development of receptor-based
      agonists and antagonists.
AB  - Estrogen-induced signaling mediated by estrogen receptors (ERs) is also affected
      by aberrant ERs that act as constitutively active or dominant negative
      modulators. Variant ERs can contribute to carcinogenesis and to the loss of
      estrogen responsiveness, rendering antiestrogen therapy ineffective. Determining
      target gene response during co-synthesis of different ER species is difficult,
      because dimers formed in the presence of more than one ER species are a
      heterogenous population of homo- or heterodimers. We engineered a homofusion
      ERalpha as a prototype single-chain receptor by genetically conjugating two ER
      monomers into a covalently fused single-chain protein to obtain a homogeneous
      population. This permits analysis of symmetrical or asymmetrical mutations that
      simulate variant homo- and heterodimers. Although a monomer, the homofusion
      receptor exhibited similar biochemical and functional properties to the dimeric
      ERalpha. We used activation function-2 (AF2) defective mutants as a model in
      either one or both receptor domains for a dominant-negative phenotype by
      suppressing the reporter activity induced by the WT receptor. When co-expressed
      with ERalpha, the fusion variant deficient in both AF2 functions suppressed the
      reporter activity effectively induced by ERalpha. These results show the utility
      of fusion receptors as models for generation of receptor-based agonists and
      antagonists.

PMID- 11514060
TI  - PTHrP increases pancreatic beta-cell-specific functions in well-differentiated
      cells.
AB  - Parathyroid hormone-related protein (PTHrP) is reportedly produced in normal
      islets and insulinomas. PTHrP induces differentiation in some cell-types and
      growth in others. We examined whether PTHrP production is greater in well
      differentiated or growing beta cells and whether PTHrP induces differentiation or
      growth in beta cells. We used four groups of the well-differentiated mouse beta
      cell line MIN6 with 17, 25, 31 and 41 passages, and mouse pancreatic islets. With
      passage, insulin content diminished, whereas the expression of PTHrP, its
      activating enzyme furin and cell growth gradually increased. PTHrP increased
      insulin content and mRNA levels more in MIN6-17 cells than in MIN6-41 cells. In
      contrast, PTHrP increased DNA synthesis more extensively in MIN6-41 cells than in
      MIN6-17 cells. Dibutyryl cAMP reproduced PTHrP's effect on insulin content and
      DNA synthesis. We conclude that PTHrP increases insulin expression in well
      differentiated beta cells through the cAMP pathway and stimulates growth in
      growing beta cells.

PMID- 11514051
TI  - Characterization of the secretable ectodomain of thyrotropin receptor produced by
      the recombinant baculovirus system.
AB  - Thyrotropin receptor (TSHR) is a member of the glycoprotein hormone receptor
      family and an autoantigen of Graves' disease. Various attempts have been made to
      obtain a large amount of soluble ectodomain of TSHR in insect or mammalian cells,
      but most of them failed to secrete the overexpressed ectodomain. In the present
      study, we observed that about one-third of the ectodomain protein (sTSHR-gp), in
      which the signal peptide of TSHR was replaced by the baculovirus-encoded
      glycoprotein 67-signal peptide, was secreted into the culture medium and the
      remainder stayed within cells in the recombinant baculovirus system.
      Microsequencing the N-terminal of the purified protein confirmed that the
      baculovirus signal peptide was cleaved at the expected site. Carbohydrate studies
      using several glycosidases and lectins revealed that the secreted form of the
      ectodomain had biantennary carbohydrate, whereas the non-secreted form had high
      mannose. Moreover, the secreted form of sTSHR-gp exhibited high-affinity ligand
      binding, whereas the non-secreted form did not show any significant ligand
      binding. Regarding the interactions of TSHR ectodomains with anti-TSHR
      antibodies, both the secreted and non-secreted forms of sTSHR-gp, almost
      completely neutralized the stimulatory and inhibitory anti-TSHR antibody
      activities. In conclusion, we succeeded in secreting the ectodomain of TSHR into
      culture medium, which was capable of binding to TSH and neutralizing anti-TSHR
      antibody activities.

PMID- 11514056
TI  - Progesterone inhibits transcriptional activation of human chorionic gonadotropin
      alpha gene through protein kinase A pathway in trophoblast cells.
AB  - The purpose of this study was to analyze the mechanism of transcriptional
      inhibition of human chorionic gonadotropin-alpha (hCGalpha) gene by progesterone
      in trophoblast cells. We stably transfected -290 bp hCGalpha promoter-CAT
      constructs (-290halphaCAT) into Rcho-1 cells and monitored the promoter
      activities. Differentiation-dependent activation of -290 bp hCGalpha promoter
      containing a tandem repeat of cAMP response element (CRE) was inhibited by
      progesterone in a dose-dependent manner. To further analyze the mechanism of the
      progesterone action, Rcho-1 cells stably transfected with -290halphaCAT were
      treated with forskolin in the presence of progesterone. Progesterone inhibited
      forskolin-induced transcriptional activation of hCGalpha gene. Moreover,
      progesterone inhibited forskolin-induced transcriptional activation of CRE-CRE-tk
      CAT. These results suggest that progesterone may inhibit cAMP-induced
      transcriptional activation of hCGalpha gene through CRE. Although progesterone
      did not alter the amount of CRE-binding protein (CREB), which is a main
      transcriptional factor bound to CRE(s) on hCGalpha promoter, progesterone
      abolished forskolin-induced CREB phosphorylation. In addition, pretreatment with
      progesterone abolished forskolin-induced activation of nuclear protein kinase A
      (PKA). In conclusion, progesterone inhibits hCGalpha gene transcription, at least
      in part, via the CRE region by inhibiting CREB phosphorylation through PKA
      pathway in trophoblast cells.

PMID- 11514054
TI  - Age-dependent stimulation of Leydig cell steroidogenesis by interleukin-1
      isoforms.
AB  - Different isoforms of testicular interleukin-1 (IL-1) were analysed to determine
      whether there were differences in the ability to modulate rat Leydig cell
      steroidogenesis in vitro. Rat 17K IL-1alpha and IL-1beta, 32K IL-1alpha precursor
      (32proIL-1alpha) and a 24K splice variant (24proIL-1alpha) stimulated
      testosterone production by Leydig cells from 40- but not 80-day-old rats. The
      potency of the isoforms was IL-1alpha>IL-1beta>32proIL-1alpha>24proIL-1alpha, IL
      1alpha being 50-fold more potent than IL-1beta. IL-1 receptor antagonist reversed
      the effects and IL-1 receptor type I mRNA was expressed by the responding Leydig
      cells, indicating a receptor mediated action. Inhibition of PKA and Ca(2+)
      channels abolished IL-1-induced steroidogenesis, while inhibition of PKC had no
      significant effect. Except for 24proIL-1alpha which was stimulatory, all IL-1
      isoforms suppressed hCG-driven testosterone production. This inhibitory effect
      was abolished by androstendione, suggesting that P450c17 was suppressed by IL-1.
      Our results indicate that IL-1 plays a paracrine role in the regulation of Leydig
      cell steroidogenesis.

PMID- 11514050
TI  - Proteasome inhibitor enhances growth hormone-binding protein release.
AB  - We used murine Ba/F3 cells transfected with human growth hormone receptor (hGHR)
      cDNA to investigate the regulatory mechanisms of human growth hormone-binding
      protein (hGH-BP) release. The extracellular domain of hGHRs were cleaved and
      released as hGH-BPs (a soluble form of hGHR). The hGH-BP release was enhanced by
      phorbol 12,13-dibutyrate (PDBu), and suggested to be mediated by activation of
      PKC, the same as in human IM-9 cells. Thus, Ba/F3 cells have hGH-BP-releasing
      pathways similar to those of human cells. The proteasome inhibitors MG-132 and
      clasto-lactacystin beta-lactone also increased hGH-BP release from Ba/F3-hGHR
      cells, and MG-132 and PDBu synergistically increased hGH-BP release. The results
      obtained by using three PKC inhibitors Go 6976, GF 109203X and Go 6983 suggest
      that the enhancement of hGH-BP release by MG-132 and PDBu is mediated by
      different mechanisms probably involving different PKC isozymes.

PMID- 11514061
TI  - Acute restraint stress increases 5-HT7 receptor mRNA expression in the rat
      hippocampus.
AB  - The brain serotonin (5-HT) system interacts closely with the hypothalamic
      pituitary-adrenal axis. We examined the effects of stress on hippocampal 5-HT7
      receptor and corticosteroid receptor (mineralocorticoid receptor (MR) and
      glucocorticoid receptor (GR)) mRNA expression measured by in situ hybridisation
      histochemistry. Acute restraint stress increased 5-HT7 receptor mRNA in CA2 and
      CA3 hippocampal subregions (32% increase) and had a small effect on GR but not MR
      mRNA (19% fall in GR in CA1). In contrast, chronic stress (1 week of variable
      stressors) had little effect on hippocampal 5-HT7 receptor mRNA (9% rise in CA3)
      but decreased MR mRNA (e.g. 34% decrease in CA2) and GR mRNA expression
      selectively in the dentate gyrus (26% decrease). The rise in 5-HT7 receptor mRNA
      expression following restraint stress parallels our previously reported increase
      in expression after inhibiting the synthesis of adrenal steroids. These data
      suggest that acute but not chronic stress regulates 5-HT7 receptor mRNA
      expression in a manner that is likely to be independent of its glucocorticoid
      actions.

PMID- 11514057
TI  - Protein kinase C, rather than protein kinase A is involved in follicle
      stimulating hormone-mediated meiotic resumption of mouse cumulus cell-enclosed
      oocytes in hypoxanthine-supplemented medium.
AB  - It has been reported that protein kinase C (PKC) activation participated in the
      porcine and bovine oocyte maturation, but not in mouse oocyte maturation in
      vitro. In the present study, the activators and inhibitors of protein kinase A
      (PKA) (forskolin, CDPKI and MDL-12230A) or PKC (PMA, staurosporine and
      sphingosine) were used to investigate the in vitro effect of PKA or PKC on
      spontaneous murine oocyte maturation, oocyte resumption of meiosis from HX
      inhibiting medium (medium+HX), and follicle stimulating hormone (FSH)-induced
      oocyte maturation. The results showed that when cumulus cell enclosed oocytes
      (CEOs) or denuded oocytes (DOs) were cultured for 24 h in the medium supplemented
      with forskolin (5 microM), an activator of adenylate cyclase, the spontaneous
      oocyte maturation were inhibited. A transient exposure (2 h) to forskolin (2-10
      microM) in the medium+HX, and then transferred to a new medium+HX for the further
      culture, stimulated CEO resumption of meiosis. CDPKI (10(-10)-10(-6) M), an
      inhibitor of PKA, also stimulated oocyte meiotic maturation of CEO in the
      medium+HX, but not on DO. However, MDL-12230A (10(-12)-10(-9) M), an inhibitor of
      adenylate cyclase, did not promote oocyte maturation in HX arrested CEO. CDPKI
      (10(-10)-10(-6) M) or MDL-12230A (10(-12)-10(-9) M) had no effect on FSH
      stimulated oocyte meiotic resumption, except at high doses of CDPKI (10(-7)-10(
      6) M) or MDL-12230A (10(-9) M) which inhibited the FSH-induced formation of the
      first polar body (PB1). An activator of PKC, PMA (10(-11)-10(-7) M) dose
      dependently inhibited spontaneous oocyte maturation of CEO or DO. Inhibitors of
      PKC, staurosporine (10(-9)-10(-6) M) or sphingosine (10(-8)-10(-5) M) induced
      oocytes in CEOs to resume meiosis in the presence of HX in a dose dependent
      manner, but had no effect on DOs. FSH (50IU/L) stimulated mouse oocytes in CEOs
      to override the arrest of HX and resume meiosis, while PMA, at the level of 10(
      8)-10(-6) M, dramatically inhibited the stimulatory effect of FSH. These results
      indicate that PKC or PKA may be implicated in the regulation of mouse oocyte
      maturation. Thus while sustained high level of cAMP or PKA inhibit the resumption
      of meiosis, a transient rise in cAMP or PKA levels promotes oocyte maturation.
      The activation of PKC can also block oocyte meiotic resumption. Thus the
      inactivation of PKC, instead of the transient rise of PKA activity, appears to be
      involved in the process of FSH-mediated oocyte meiotic maturation.

PMID- 11514063
TI  - Radial glia-mediated up-regulation of somatostatin in the regenerating adult fish
      brain.
AB  - Adult teleost fish, Apteronotus leptorhynchus, exhibit an enormous regenerative
      capability after application of mechanical lesions to the dorsalmost subdivision
      of the cerebellum, the corpus cerebelli. Restoration of the neural tissue is
      achieved by a cascade of processes, including the guidance of migrating new
      neurons to the site of injury by radial glial fibers. These fibers are
      characterised by the expression of immunoreactive glial fibrillary acidic protein
      and by several morphological features. Within 12 h following the lesion, the
      fraction of radial glial fibers expressing the neuropeptide somatostatin (SRIF)
      dramatically increased from approximately 1%, as found in the intact brain, to
      roughly 27% 12-24 h post-lesion. Subsequently, the percentage of SRIF-expressing
      radial glial fibers gradually declined, until it reached background levels at
      about 10 days following the injury. We hypothesise that the expression of SRIF is
      related to the generation and/or differentiation of the new neurons produced in
      response to the lesion, rather than to the later guidance of these cells along
      their migratory pathway.

PMID- 11514062
TI  - Insulin receptor substrate protein p53 localization in rats suggests mechanism
      for specific polyglutamine neurodegeneration.
AB  - Dentatorubral-pallidoluysian atrophy (DRPLA) is a neurodegenerative disease that
      results from the expansion of an unstable CAG repeat within the coding regions of
      the DRPLA gene. Recently it was shown that the DRPLA gene product, atrophin-1,
      interacts with the human insulin receptor tyrosine kinase substrate protein,
      IRSp53. We have isolated rat and mouse cDNA clones for IRSp53 and determined
      expression patterns in rat central nervous system. In situ hybridization analysis
      revealed enriched IRSp53 mRNA expression in rat forebrain structures, including
      the cerebral cortex (layers II/III, V and VI), striatum, hippocampus and
      olfactory bulb. IRSp53 hybridization signals were also detected in the
      cerebellum, subthalamic nucleus, pons, amygdala and hypothalamus. These findings
      support the idea that insulin and insulin growth factor-1 have a role in
      neurotransmission, one that is regionally specific. The expression of IRSp53 in
      regions similar to those that degenerate in DRPLA supports the notion that IRSp53
      is a relevant atrophin-1 binding protein and may provide a mechanism for region
      specific neurodegeneration.

PMID- 11514064
TI  - Chronic imipramine treatment partially reverses the long-term changes of
      hippocampal synaptic plasticity in socially stressed rats.
AB  - In the present study, we investigated whether synaptic plasticity changes in the
      hippocampus of depressive-like socially stressed rats could be reversed by
      chronic antidepressant treatment. To that end, rats were either defeated and
      subsequently individually housed or subjected to control treatment followed by
      social housing. After a period of at least 3 months, rats were either treated
      chronically with imipramine (20 mg/kg per day, per os for at least 3 months) or
      the solvent solution (i.e. water). Then, long-term potentiation and depression
      were measured in the CA1 region of the hippocampus in vitro. Chronic imipramine
      treatment partially restored the attenuated induction of long-term potentiation
      and suppressed the facilitation of long-term depression-induction in socially
      stressed rats. The altered synaptic plasticity after social stress is discussed
      in relation to cognitive deficits and hippocampal changes that are observed in
      depressive patients.

PMID- 11514065
TI  - Biphasic modulation of nociceptive processing by the cyclic AMP-protein kinase A
      signalling pathway in sheep spinal cord.
AB  - A role for the cyclic AMP (cAMP)-protein kinase A (PKA) transduction cascade in
      nociceptive processing has been identified. This study examined the effects of
      intrathecal treatment with the cAMP analogue 8-Bromo-cAMP and the PKA inhibitor H
      89 dihydrochloride on nociceptive thresholds to mechanical stimulation in six
      adult sheep to define further the role of cAMP in spinal nociception. Treatment
      with 420 nmol 8-Br-cAMP induced significant hypoalgesia to noxious stimulation,
      while a 10-fold higher dose (4.2 micromol) induced mechanical hyperalgesia. Both
      of these behaviours were blocked by H-89 (38-380 nmol). Treatment with high dose
      H-89 (380 nmol) alone significantly increased nociceptive thresholds. These
      results demonstrate that activation of the cAMP-PKA signalling pathway modulates
      acute nociceptive events in spinal cord in a biphasic manner, and suggest that
      significant tonic activity exists in this pathway.

PMID- 11514066
TI  - Intrastriatal injection of D1 or D2 dopamine agonists affects glucose utilization
      in both the direct and indirect pathways of the rat basal ganglia.
AB  - Two distinct pathways are thought to connect the striatum to the basal ganglia
      output nuclei: a direct pathway, originating from neurons bearing dopamine, D(1)
      receptors and an indirect pathway, originating from neurons expressing D(2)
      receptors. It has been recently suggested, however, that dopamine receptor sub
      types may co-localize and co-operate in the striatum. We sought to verify the
      functional segregation of the two pathways by measuring cerebral glucose
      utilization following intrastriatal injection of selective D(1) (SKF 38393), D(2)
      (quinpirole), or non-selective indirect (amphetamine) and direct (apomorphine)
      dopamine agonists, in freely-moving rats. All drugs -- regardless of receptor
      selectivity -- reduced glucose utilization in nuclei of both the direct and
      indirect pathways, thus lending further support to the existence of a functional
      co-operation of striatal D(1) and D(2) receptors.

PMID- 11514067
TI  - Lowering glucose concentrations increases cytosolic Ca2+ in orexin neurons of the
      rat lateral hypothalamus.
AB  - Orexin neurons are specifically localized in and around the lateral hypothalamus
      (LH), a feeding center. Intracerebroventricular administration of orexin-A and -B
      stimulates feeding as well as arousal. However, little is known regarding the
      regulators of the orexin neuron activity. The neurons that are activated under
      low glucose conditions, glucose-sensitive neurons, are located in the LH and have
      been implicated in the control of feeding. The present study investigated the
      effect of glucose on the single orexin neurons isolated from the rat LH, by
      measuring cytosolic Ca(2+) concentration ([Ca(2+)](i)) by fura-2 microfluorometry
      followed by immunocytochemical staining with anti-orexin antiserum. A shift of
      glucose concentration form 8.3 to 2.8 mM in the superfusion solution increased
      [Ca(2+)](i) in 13 out of 32 orexin-immunoreactive LH neurons. The results
      demonstrate that glucose-sensitive orexin neurons are present in the LH and that
      these neurons may play a role in linking the metabolic state in the body to the
      orexigenic, and could also, awakening signaling in the brain.

PMID- 11514068
TI  - Resistance of PC12 cells against nitric oxide (NO)-induced toxicity in long-term
      culture: implication of neuronal NO synthase expression.
AB  - We have previously reported that a nitric oxide (NO)-donor, (+/-)-(E)-4-ethyl-2
      [(E)-hydroxyimino]-5-nitro-3-hexenamide (NOR3) induced cell death even at a low
      concentration in undifferentiated PC12 cells. In the present study, we found that
      PC12 cells which were cultured long-term for over 80 passages acquired resistance
      to the NOR3-induced cell toxicity. After 24 h exposure to 10-100 microM NOR3, a
      concentration-dependent cell death was observed in short-term cultured PC12 cells
      (8-30 passages), but not in long-term cultured cells (over 80 passages). In the
      cells cultured short-term, the cell death was accompanied by nuclear condensation
      and fragmentation. We further examined the alterations in total glutathione (GSH)
      levels, and activities of antioxidant enzymes, superoxide dismutase (SOD) and
      catalase in the short- and long-term cultured PC12 cells. SOD activity decreased
      in the long-term cultured cells, while catalase activity did not change. The GSH
      content significantly increased in the cells cultured long-term. Furthermore, the
      long-term but not the short-term cultured cells, expressed neuronal NO synthase
      (nNOS), but neither endothelial nor inducible NOS. These findings suggest that
      the PC12 cells acquire resistance to the NO-induced toxicity, accompanied by an
      increase in the GSH level and the expression of nNOS after long-term culture.

PMID- 11514069
TI  - Substantial loss of substrate by diffusion during uptake in HEK-293 cells
      expressing neurotransmitter transporters.
AB  - Human embryonic kidney 293 (HEK-293) cells stably transfected with the human
      serotonin (5-HT) or dopamine transporter (hSERT, hDAT), or the rat GABA
      transporter GAT-1 were incubated with saturating concentrations of transporter
      substrates (hSERT: [(3)H]5-HT, [(3)H]N-methyl-phenyl-pyridinium (MPP+); hDAT:
      [(3)H]dopamine, [(3)H]MPP(+); rGAT: [(3)H]GABA). Uptake velocities decreased
      significantly over time for [(3)H]5-HT and [(3)H]dopamine (already visible at 1
      min), but not for [(3)H]MPP(+) or [(3)H]GABA. In efflux experiments cells were
      preloaded and substrate diffusion into the medium was studied following the
      addition of appropriate uptake inhibitors. Fractional effluxes were (% min(-1))
      1.27, 0.72, 0.27 and 0.08 for [(3)H]5-HT, [(3)H]dopamine, [(3)H]MPP(+) and
      [(3)H]GABA, respectively. The results suggest that in uptake experiments the more
      lipophilic substrates [(3)H]5-HT and [(3)H]dopamine leave the cells by diffusion
      already after a short time (1 min) of accumulation.

PMID- 11514070
TI  - Receptor binding properties of di (1,N6-ethenoadenosine) 5', 5'''-P1, P4
      tetraphosphate and its modulatory effect on extracellular glutamate levels in rat
      striatum.
AB  - Our aim was to investigate the neuromodulatory role of diadenosine tetraphosphate
      (Ap(4)A). Ap(4)A-binding sites were detected in striatum and hippocampus
      membranes using [(35)S]-ADP beta S as radioligand and Ap(4)A and epsilon
      (Ap(4)A), di-ethenoadenosine tetraphosphate, as displacers. Effects of epsilon
      (Ap(4)A) on extracellular glutamate levels were studied using intracerebral
      perfusion. Both areas contain high-affinity binding sites for [(35)S]-ADP beta S
      with K(d) values in the low nM range. [(35)S]-ADP beta S binding was displaced by
      Ap(4)A and epsilon-(Ap(4)A). At 1 and 10 microM doses, epsilon-(Ap(4)A) markedly
      decreased glutamate levels in the striatum. The possibility of Ap(4)A acting as
      an endogenous modulator of excitatory neurotransmission is discussed.

PMID- 11514071
TI  - Adenosine inhibits glutamate exocytosis largely without interfering with Ca2+
      influx in rat cerebrocortical synaptosomes.
AB  - Adenosine is an inhibitor of glutamate release in synaptosomes. The inhibition is
      removed by the A(1) adenosine receptor antagonist 8-cyclopentyl-1,3
      dipropylxanthine (DPCPX). We monitored the variations of cytoplasmic free Ca(2+)
      concentrations ([Ca(2+)](i)) in KCl or 4-aminopyridine-stimulated synaptosomes,
      in the presence of adenosine or adenosine plus DPCPX. The increment of
      [Ca(2+)](i) upon stimulation was unmodified by adenosine (up to 400-500 microM)
      while it was strongly decreased when exocytosis was decreased to a similar extent
      by lowering KCl or 4-aminopyridine. Adenosine also inhibited glutamate release
      induced by the Ca(2+) ionophore ionomycin. Increasing adenosine to 1.5 mM
      resulted in a decrease of the stimulus-induced increase of [Ca(2+)](i) and in the
      further potentiation of the adenosine inhibition of exocytosis from 41+/-3 to
      51+/-4%. We conclude that adenosine affects glutamate exocytosis mostly in a
      Ca(2+) independent mode.

PMID- 11514072
TI  - Amplitude reduction of the mismatch negativity in first-degree relatives of
      patients with schizophrenia.
AB  - First-degree relatives of schizophrenic patients display alterations in various
      cognitive domains and their electrophysiological counterparts similar to
      schizophrenic subjects. The mismatch negativity (MMN) is an event-related
      potential that reflects sensory memory in the pre-attentive stage of auditory
      processing. An amplitude reduction of the MMN has been reported in schizophrenia.
      The present study investigated the MMN in patients with schizophrenia, first
      degree relatives and control subjects. The MMN amplitude was reduced in relatives
      compared to controls. The MMN amplitude reduction in schizophrenic patients
      compared to controls, however, did not reach significance in the present study.
      These results provide first evidence for disturbed sensory memory in relatives of
      patients with schizophrenia.

PMID- 11514073
TI  - Nicotinic receptors in Lymnaea stagnalis neurons are blocked by alpha-neurotoxins
      from cobra venoms.
AB  - The influence of cobra neurotoxins on the Cl-dependent responses to acetylcholine
      (ACh) of Lymnaea neurons was studied by the voltage-clamp technique. It was found
      that a short chain neurotoxin II (NT II), a long chain cobratoxin (CTX) and weak
      neurotoxin (WTX) diminished the ACh-induced currents, the block being
      concentration-dependent and competitive. The IC(50) values of 130 nM for CTX, 11
      microM for NT II, and 67 microM for WTX were determined. The block induced by NT
      II was quickly reversible upon toxin washout, whereas the action of CTX and WTX
      was only partially reversible even after an hour of intensive washing. The data
      obtained suggest that acetylcholine receptors (AChRs) in Lymnaea neurons have
      common features with cation-selective alpha 7 AChRs of vertebrates and one type
      of Aplysia Cl-conducting AChRs.

PMID- 11514074
TI  - Phospholipid fatty acids and neurotoxicity in human neuroblastoma SH-SY5Y cells.
AB  - The fatty acid composition of phospholipids from differentiated human
      neuroblastoma SH-SY5Y cells, human and rat brain tissue and rat brain
      synaptosomes was determined using high pressure liquid chromatography. Comparison
      of the fatty acid composition of the cells with that derived from brain tissue
      identified differences in the cells including a profound deficit of
      docosahexaenoic acid and an elevation of arachidonic acid. The phospholipid fatty
      acid content could be modified by addition of free fatty acids to the growth
      medium, and this was shown to influence the susceptibility of the SH-SY5Y cells
      to the cell death induced by a mitochondrial toxin, 3-nitropropionic acid.

PMID- 11514075
TI  - Activation of the CB1 cannabinoid receptor protects cultured mouse spinal neurons
      against excitotoxicity.
AB  - Significant advances are being made towards understanding the genetic basis for
      spinal neurodegenerative diseases, however, effective pharmacotherapy remains
      elusive. One of the primary theories underlying neuron vulnerability is
      susceptibility to excitotoxicity. We present for the first time evidence that the
      activation of the CB(1) cannabinoid receptor effectively modulates kainate
      toxicity in primary neuronal cultures prepared from mouse spinal cord. Addition
      of Delta(9)-tetrahydrocannabinol to the culture medium attenuated the toxicity
      produced by kainate. The CB(1) receptors were localized to spinal neurons and
      astrocytes. The neuroprotective effect was blocked with the CB(1) receptor
      antagonist, SR141716A, indicating a receptor-mediated effect.

PMID- 11514076
TI  - Expression of glycine receptors in rat sensory neurons vs. HEK293 cells yields
      different functional properties.
AB  - Many structure-function studies of the glycine receptor (GlyR), and other ligand
      gated ion channels, use somatic cell lines or Xenopus oocytes as expression
      systems. Using a polyethylenimine-based technique, we transfected GlyR cDNA into
      primary cultures of rat dorsal root ganglion (DRG) neurons. We then compared the
      functional properties of wildtype and a mutant GlyR expressed in DRG neurons with
      HEK 293 cells. The glycine sensitivity of the wildtype GlyR was nearly identical
      for the two cell types. The mutant GlyR has an arginine for glutamine
      substitution at position 271 (R271Q), which results in low glycine sensitivity
      relative to wildtype receptors expressed in HEK cells. This point mutation is
      associated with startle disease (hyperekplexia) in humans. Mutant GlyR expression
      in DRG neurons resulted in a significantly lower glycine sensitivity than was
      seen in HEK cells. This supports the idea that neuron-specific post-translational
      modifications may be important for determining receptor function.

PMID- 11514077
TI  - Examination of estradiol effects on the rapid estradiol mediated increase in
      hippocampal synaptic transmission in estrogen receptor alpha knockout mice.
AB  - Hippocampal slices from rats exhibit a rapid increase in basal synaptic
      transmission following 17 beta-estradiol (E(2)) application. In the current study
      we examined the role of the classic genomic receptor, estrogen receptor alpha (ER
      alpha), in mediating E(2) effects on synaptic transmission. E(2) (100 pM)
      increased the extracellular synaptic response in hippocampal slices from
      gonadectomized male and female mice lacking a functional ER alpha knockout (ER
      alpha KO) and wild-type (WT) littermates. No sexually dimorphic differences were
      observed, however, the increase in the field potential was more pronounced in WT
      mice. ER antagonists did not block E(2) mediated growth of the synaptic response
      in ER alpha KO mice. The results suggest that the rapid effect of E(2) on
      synaptic transmission is not mediated by ER alpha, however, ER alpha appears to
      modulate non-genomic influences on synaptic transmission.

PMID- 11514078
TI  - Spinal cord glia: new players in pain.

PMID- 11514079
TI  - Methionine-enkephalin-and Dynorphin A-release from immune cells and control of
      inflammatory pain.
AB  - We have previously shown that beta-endorphin (END) is contained and released from
      memory-type T-cells within inflamed tissue and that it is capable to control pain
      (J Clin Invest 100(1) (1997) 142). Methionine-enkephalin (MET) and Dynorphin-A
      (DYN) are endogenous opioids with preference for delta- and kappa-opioid
      receptors, respectively. Both MET and DYN are produced and contained within
      immune cells. The goal of this study was to determine the release characteristics
      of MET and DYN in a rat model of localized hindpaw inflammation and to examine
      the antinociceptive role of MET and DYN in a Freund's adjuvant induced model of
      inflammatory pain. We found that corticotropin-releasing factor (CRF) can
      stimulate the release of both MET and DYN from lymphocytes. This release is dose
      dependent and reversible by the selective CRF antagonist alpha-helical-CRF.
      Furthermore, CRF (1.5 ng) produces analgesia when injected into the inflamed paw,
      which is reversible by direct co-administration of antibodies to MET. Lymphocyte
      content of MET was 7.0+/-1.4 ng/million cells, whilst DYN content was ~30-fold
      lower. Both END and DYN, but not MET, were released by IL-1. Consistently, IL-1
      produced peripheral analgesic effects which were not reversed by antibodies to
      MET. These results indicate that both MET and DYN play a role in peripheral
      analgesia but have different characteristics of release. These studies further
      support a role of the immune system in the control of inflammatory pain. This may
      be particularly important in patients suffering from compromised immune systems
      as with cancer and AIDS.

PMID- 11514080
TI  - Substance P, calcitonin gene related peptide and PGE2 co-released from the mouse
      colon: a new model to study nociceptive and inflammatory responses in viscera, in
      vitro.
AB  - Visceral inflammation is thought to play an important role in the sensitization
      of low and high threshold mechanosensory and polymodal afferents and to recruit
      silent nociceptors. Yet, little is known about the potential role of the
      mediators involved in nociceptor sensitization to mechanical stimulation as
      compared to heat sensitization in the skin. In the present study we developed a
      new isolated preparation of the mouse colon which allowed to apply controlled
      mechanical distensions. Excised segments of colon from CD mice were immersed in
      synthetic interstitial fluid (SIF) exposing the serosal surface during 5 min to
      different types of noxious stimuli; the increase in neuropeptide and PGE(2)
      release were analyzed (by EIA technique). Capsaicin, heat and pH 5.2 were able to
      induce significant increases in calcitonin gene related peptide (CGRP) release
      (14.6-, 5.1-, and 2.3-fold over baseline), however, only capsaicin induced a
      significant increase in substance P (SP) levels (1.8-fold over baseline). When pH
      3.4 was used, a massive liberation of both CGRP and SP was obtained (14- and 15
      fold from baseline) which was Ca(2+)-independent and not recovering, suggesting
      unphysiological release. Mechanical distensions in the noxious range (45, 60 and
      90 mmHg) evoked a long-linear graded release of CGRP (1.3-, 1.6- and 2.6-fold
      over baseline) and of PGE(2) (1.9- 3.8-, 12.3-fold over baseline). Only the 90
      mmHg distension evoked a significant increase of SP (1.9-fold over baseline). We
      conclude that the mouse colon preparation is a suitable model to study
      inflammatory and nociceptive mechanisms in viscera. Furthermore, a potentially
      important and yet unexplored role of PGE(2) in noxious visceral distension has
      been revealed.

PMID- 11514081
TI  - Antihyperalgesic effects of the muscarinic receptor ligand vedaclidine in models
      involving central sensitization in rats.
AB  - It is well established that muscarinic cholinergic agonists produce
      antinociceptive effects in a number of acute pain models. However, relatively
      little is known about the effects of muscarinic receptor agonists in models which
      involve central sensitization in pain pathways. The purpose of the present
      studies was to evaluate the effects of vedaclidine, a muscarinic receptor mixed
      agonist/antagonist across receptor subtypes, in models involving central
      sensitization. Vedaclidine (0.3-10 mg/kg s.c.) produced dose-related
      antihyperalgesic effects in the formalin test as well as a dose-related reversal
      of capsaicin-induced mechanical hyperalgesia in rats. In the carrageenan test,
      vedaclidine (0.1-30 mg/kg) produced a dose-related reversal of both mechanical
      and thermal hyperalgesia that were antagonized by the muscarinic receptor
      antagonist scopolamine. In addition, the antihyperalgesic effects of vedaclidine
      in the carrageenan test were synergistic with the antihyperalgesic effects of the
      non-steroidal antiinflammatory drug ketoprofen, as demonstrated by isobolographic
      analysis. The present studies demonstrate that vedaclidine produces
      antihyperalgesic effects in models involving central sensitization, suggesting
      that vedaclidine, and potentially other muscarinic receptor agonists, may have
      clinical utility in the management of pain states involving central
      sensitization, such as neuropathic and inflammatory pain states.

PMID- 11514082
TI  - The impact of psychologically different patient groups on outcome after a
      vocational rehabilitation program for long-term spinal pain patients.
AB  - A better knowledge of differential treatment outcomes for subgroups of chronic
      spinal pain patients may, for instance, help clinicians in treatment planning or
      pain researchers in treatment outcome research. The purpose of this prospective
      study was to evaluate the predictive validity of a subgroup classification based
      on the Swedish version of the (West Haven Yale) Multidimensional Pain Inventory,
      the MPI-S. Patients referred to a vocational rehabilitation program were
      classified into one of three groups, labeled 'adaptive copers', 'dysfunctional'
      patients, and 'interpersonally distressed' patients, and followed over an 18
      month follow-up period. The outcome variables were absence from work (defined as
      sick listing plus early retirement), general health status, and utilization of
      health care resources. To our knowledge, the predictive validity of the MPI
      subgroups has not been evaluated regarding sick listing and early retirement
      after rehabilitation. As hypothesized, the results showed that the
      'dysfunctional' patient group had significantly more registered absences from
      work and reported higher utilization of health care, over the follow-up period
      compared to the 'adaptive copers'. Furthermore, as hypothesized, the
      'interpersonally distressed' and 'dysfunctional' patient groups report a poorer
      general health status than the 'adaptive copers' over the whole follow-up period.
      However, contrary to our hypothesis, the proportion of improved patients did not
      differ significantly between the subgroups. Altogether, the predictive validity
      of the MPI-S subgroup classification was mainly confirmed. The clinical
      implications of this study suggest that the matching of treatment to patient
      needs may enhance treatment outcome, reduce pain and suffering among chronic
      spinal pain patients and facilitate a better health economic allocation of
      treatment resources.

PMID- 11514083
TI  - CB2 cannabinoid receptor-mediated peripheral antinociception.
AB  - Cannabinoid receptor agonists diminish responses to painful stimuli. Extensive
      evidence implicates the CB(1) receptor in the production of antinociception.
      However, the capacity of CB(2) receptors, which are located outside the central
      nervous system (CNS), to produce antinociception is not known. Using AM1241, a
      CB(2) receptor-selective agonist, we demonstrate that CB(2) receptors produce
      antinociception to thermal stimuli. Injection of AM1241 in the hindpaw produced
      antinociception to a stimulus applied to the same paw. Injection of an equivalent
      dose of AM1241 into the paw contralateral to the side of testing did not. The
      antinociceptive actions of AM1241 were blocked by the CB(2) receptor-selective
      antagonist AM630, but not by the CB(1) receptor-selective antagonist AM251.
      AM1241 also produced antinociception when injected systemically
      (intraperitoneally). The antinociceptive actions of systemic AM1241 were blocked
      by injection of AM630 into the paw where the thermal stimulus was applied, but
      not the contralateral paw. These findings demonstrate the local, peripheral
      nature of CB(2) cannabinoid antinociception. AM1241 did not produce the CNS
      cannabinoid effects of hypothermia, catalepsy, inhibition of activity or impaired
      ambulation, while this tetrad of effects was produced by the mixed CB(1)/CB(2)
      receptor agonist WIN55,212-2. Peripheral antinociception without CNS effects is
      consistent with the peripheral distribution of CB(2) receptors. CB(2) receptor
      agonists may have promise clinically for the treatment of pain without CNS
      cannabinoid side effects.

PMID- 11514084
TI  - Symptoms during cancer pain treatment following WHO-guidelines: a longitudinal
      follow-up study of symptom prevalence, severity and etiology.
AB  - Most patients with advanced cancer develop diverse symptoms that can limit the
      efficacy of pain treatment and undermine their quality of life. The present study
      surveys symptom prevalence, etiology and severity in 593 cancer patients treated
      by a pain service. Non-opioid analgesics, opioids and adjuvants were administered
      following the WHO-guidelines for cancer pain relief. Other symptoms were
      systematically treated by appropriate adjuvant drugs. Pain and symptom severity
      was measured daily by patient self-assessment; the physicians of the pain service
      assessed symptom etiology and the severity of confusion, coma and
      gastrointestinal obstruction at each visit. The patients were treated for an
      average period of 51 days. Efficacy of pain treatment was good in 70%,
      satisfactory in 16% and inadequate in 14% of patients. The initial treatment
      caused a significant reduction in the average number of symptoms from four to
      three. Prevalence and severity of anorexia, impaired activity, confusion, mood
      changes, insomnia, constipation, dyspepsia, dyspnoea, coughing, dysphagia and
      urinary symptoms were significantly reduced, those of sedation, other
      neuropsychiatric symptoms and dry mouth were significantly increased and those of
      coma, vertigo, diarrhea, nausea, vomiting, intestinal obstruction, erythema,
      pruritus and sweating remained unchanged. The most frequent symptoms were
      impaired activity (74% of days), mood changes (22%), constipation (23%), nausea
      (23%) and dry mouth (20%). The highest severity scores were associated with
      impaired activity, sedation, coma, intestinal obstruction, dysphagia and urinary
      symptoms. Of all 23 symptoms, only constipation, erythema and dry mouth were
      assessed as being most frequently caused by the analgesic regimen. In conclusion,
      the high prevalence and severity of many symptoms in far advanced cancer can be
      reduced, if pain treatment is combined with systematic symptom control.
      Nevertheless, general, neuropsychiatric and gastrointestinal symptoms are
      experienced during a major part of treatment time and pain relief was inadequate
      in 14% of patients. Cancer pain management has to be embedded in a frame of
      palliative care, taking all the possibilities of symptom management into
      consideration.

PMID- 11514085
TI  - Clinical precision of myofascial trigger point location in the trapezius muscle.
AB  - Myofascial trigger points (TrPs) have been clinically described as discrete areas
      of muscle tenderness presenting in taut bands of skeletal muscle. Using well
      defined clinical criteria, prior investigations have demonstrated interrater
      reliability in the diagnosis of TrPs within a given muscle. No reports exist,
      however, with respect to the precision with which experienced clinicians can
      determine the anatomic locations of TrPs within a muscle. This paper details a
      study wherein four trained clinicians achieved statistically significant
      reliability (see below) in estimating the precise locations of latent TrPs in the
      trapezius muscle of volunteer subjects (n=20). To do so, the clinicians trained
      extensively together prior to the study. The precise anatomic location of each
      subject's primary TrP was measured in a blinded fashion using a 3 dimensional (3
      D) camera system. Use of this measurement system permitted the anatomic co
      ordinates of each TrP to be located without providing feedback to subsequent
      clinicians. The clinicians each used a pressure algometer along with patient
      feedback to document the sensitivity of each suspected TrP site, however unlike
      routine clinical practice, the algometry was performed with a double-blinded
      approach hence the results were only examined post-hoc. At the time of data
      collection (algometry readings unknown), 16 of the 20 subjects were judged to
      present with a latent TrP. Subsequently, when subjected to a criterion pressure
      threshold value of <3.0 kg.cm(-2), 12 of these TrPs were classified as being
      clinically sensitive. To assess the 3-D measurement precision, and the
      reliability of the TrP estimates, statistical measures of the SEM and the
      Generalizability coefficient (G-coeff) were determined for all suspected TrP
      sites in the superior-inferior, medial-lateral and anterior-posterior directions.
      The best results were determined by pooling the measurements of all 4 clinicians,
      however, based upon exceeding a criterion reliability threshold of 80%, the use
      of just two testers was found to produce reliable results. The two-tester
      condition yielded a precision of 7.5, 7.6 and 6.5 mm (SEM) with reliability (G
      coeff) of 0.92, 0.86 and 0.83, respectively. Given the double-blinded
      methodology, the use of pressure algometry was also found to demonstrate internal
      validity. The algometer responses associated with TrP estimates varied inversely
      with respect to the clinical group's reliability in identify the TrP locations.
      To summarize, for the trapezius muscle, this study demonstrates that two trained
      examiners can reliably localize latent TrPs with a precision that essentially
      approaches the physical dimensions of the clinician's own fingertips. Finally, it
      should be recognized that the ability to precisely document TrP location appears
      critical to the success of future studies that may be designed to investigate the
      etiology and pathogenesis of this commonly diagnosed clinical disorder.

PMID- 11514086
TI  - Endogenous galanin potentiates spinal nociceptive processing following
      inflammation.
AB  - We have undertaken a series of experiments using galanin null mutant mice to
      better define the role of endogenous galanin in spinal excitability following
      inflammation and in response to centrally sensitizing stimuli. We have employed a
      behavioural paradigm, the formalin test, as a model of tonic nociception in both
      galanin knock-out (gal-/-) and wild-type (gal+/+) mice. In this model, we find
      that gal-/- mice are markedly hypo-responsive, especially in the second phase
      response. Additionally, we have examined the thermal hyperalgesia which develops
      following peripheral injection of carrageenan into the plantar surface of one
      hindpaw. In this inflammatory paradigm, thermal hyperalgesia is markedly
      attenuated in gal-/- mice. These behavioural findings suggest that endogenous
      galanin contributes to nociceptive processing. We have tested this hypothesis
      further by employing an electrophysiological measure of spinal excitability, the
      flexor withdrawal reflex in gal-/- and gal+/+ mice. We found no differences in
      acute reflex responses to single stimuli at C-fibre strength or in the time
      course and magnitude of wind-up induced by a short conditioning train between non
      inflamed gal+/+ and gal-/- mice. However, the long-lasting post-conditioning
      enhancement of reflex excitability was only seen in gal+/+ mice. Moreover,
      following carrageenan inflammation, there was a marked increase in spinal
      nociceptive reflex excitability in the inflamed gal+/+ mice, but this enhanced
      excitability was absent in gal-/- animals. These findings illustrate that
      endogenous galanin is necessary for the full expression of central sensitization,
      and as such, plays a critical role in the development of hyperalgesia following
      peripheral tissue injury.

PMID- 11514087
TI  - Quantitative sensory testing, neurophysiological and psychological examination in
      patients with complex regional pain syndrome and hemisensory deficits.
AB  - Based on bed-side neurological testing, it has recently been shown that 33% of
      chronic complex regional pain syndrome (CRPS) type I patients exhibit sensory
      impairments, which extend past the painful area of the affected limb in a
      hemisensory distribution (Pain, 80 (1999) 95). In the present study, the
      clinically observed changes in touch and temperature sensations on the side of
      the body ipsilateral to the affected limb were investigated quantitatively.
      Neurophysiological and psychological examinations were conducted to detect
      changes in the peripheral and central nervous system as well as
      psychopathological abnormalities. In 40 patients with CRPS, a bed-side
      neurological examination was performed. Quantitative sensory testing was
      conducted at five locations on each side of the body. The evaluation of touch
      thresholds was performed using von Frey filaments (n=40). To measure cool, warm
      and heat pain thresholds quantitatively, a thermal stimulator using a Peltier
      element was used (n=28). With respect to clinical findings, the initiating trauma
      and severity of abnormalities on nerve conduction testing, three patients were
      diagnosed as having a reliable CRPS II (causalgia) and five patients a possible
      CRPS II. Thirty-two patients were diagnosed as having a CRPS I.On clinical
      examination, 15 patients revealed generalized sensory deficits on the side of the
      body ipsilateral to the affected limb (hemisensory deficit, n=12; sensory
      impairment in the upper quadrant of the body, n=3). Patients with these
      generalized sensory deficits had a significantly longer illness duration (P<0.05)
      and a significantly higher percentage of mechanical allodynia/hyperalgesia than
      patients with spatially restricted sensory deficits (n=25) (P<0.05). In patients
      with generalized sensory impairment, thresholds for touch, warm and cold
      sensations, and for heat pain were significantly increased at all five locations
      tested ipsilaterally compared with the contralateral body side, except for the
      cool threshold on the chest and the heat pain threshold distally on the affected
      limb. In patients with sensory deficits limited to the affected limb, the touch
      threshold was significantly higher only in the distal part of the affected limb
      when compared with the contralateral limb. In these patients, thermal testing
      revealed almost no differences in cool, warm and heat pain thresholds when
      comparing both sides. Repeated thermal testing conducted in five patients with
      generalized sensory impairment reproduced the significant differences between
      both sides for cool, warm and heat pain thresholds. However, the correlation
      between the results obtained in the first and second examinations was poor.
      Neurophysiological recordings revealed pathological results in 46% for nerve
      conduction studies, 24% for somatosensory evoked potentials and 39% for
      sympathetic skin response. For all methods applied, there was no statistically
      significant difference in the incidence of pathological results between patients
      with generalized and patients with spatially restricted sensory abnormalities.
      Psychological examination using the structured clinical interview on DSM-IV
      (SKID) demonstrated a high frequency of affective and anxiety disorders, however,
      without significant differences between both groups.We conclude that hemisensory
      impairment in patients with CRPS Type I is probably related to functional
      disturbances in processing of noxious events in the thalamus and may be a
      clinical correlate of subcortical brain plasticity in chronic pain.

PMID- 11514088
TI  - Increased phosphorylation of cyclic AMP response element-binding protein (CREB)
      in the superficial dorsal horn neurons following partial sciatic nerve ligation.
AB  - Partial sciatic nerve injury causes neuropathic pain associated with behavioral
      changes such as spontaneous pain, hyperalgesia and allodynia. Both central and
      peripheral sensitization of pain pathways are likely to be involved in these
      alterations. Nerve injury induced plastic changes in the dorsal horn, where the
      second relay nociceptive neurons are located, may contribute to the central
      sensitization process. It is thus important to establish the intracellular events
      through which a partial nerve injury can induce plasticity leading to neuropathic
      pain. In this study, we investigated whether partial sciatic nerve ligation
      (PSNL), a well-characterized neuropathic pain model, is able to induce the
      phosphorylation of a transcription factor, known as the cyclic AMP response
      element-binding protein (CREB) which is believed to be involved in the
      transcriptional regulation of many genes. Using immunocytochemistry, we found
      that 3 weeks following PSNL, the number of phosphorylated (p) CREB-IR cells was
      significantly increased in the injured side dorsal horn of rats, particularly in
      the superficial laminae. Interestingly, the majority of pCREB-IR cells expressed
      protein kinase Cgamma, an enzyme shown to be involved in the development of
      neuropathic pain in PSNL model. Taken together, these results suggest that
      increased CREB phosphorylation induced by PSNL may be one of the key molecular
      events leading to synaptic alterations and persistent pain in the PSNL model of
      neuropathic pain.

PMID- 11514090
TI  - Risk factors for neck pain: a longitudinal study in the general population.
AB  - The objective of the study was to examine the 1-year cumulative incidence of
      episodic neck pain and to explore its associations with individual risk factors,
      including a history of previous neck injury. A baseline cross-sectional survey of
      an adult general population sample made up of all 7669 adults aged 18-75 years,
      registered with two family practices in South Manchester, United Kingdom,
      identified the study population of adults with no current neck pain. This study
      population was surveyed again 12 months later to identify all those who had
      experienced neck pain during the follow-up period. At follow-up, cumulative 1
      year episode incidence of neck pain was estimated at 17.9% (95% confidence
      interval 16.0-19.7%). Incidence was independent of age, but was more common in
      women. A history of previous neck injury at baseline was a significant risk
      factor for subsequent neck pain in the follow-up year (risk ratio 1.7, 95%
      confidence interval 1.2-2.5), independent of gender and psychological status.
      Other independent baseline risk factors for subsequent neck pain included number
      of children, poor self-assessed health, poor psychological status and a past
      history of low back pain. We have carried out a prospective study in a general
      population sample and demonstrated that established risk factors for chronic pain
      predict future episodes of neck pain, and shown that in addition a history of
      neck injury is an independent and distinct risk factor. This finding may have
      major public health and medicolegal implications.

PMID- 11514089
TI  - Cannabinoids attenuate capsaicin-evoked hyperalgesia through spinal and
      peripheral mechanisms.
AB  - Previous studies in our laboratory have demonstrated that cannabinoids
      administered intravenously attenuate the duration of nocifensive behavior and
      block the development of hyperalgesia produced by intraplantar injection of
      capsaicin. In the present study, we extended these observations and determined
      whether cannabinoids attenuate capsaicin-evoked pain and hyperalgesia through
      spinal and peripheral mechanisms, and whether the antihyperalgesia was receptor
      mediated. Separate groups of rats were pretreated 7 min before capsaicin with an
      intrathecal injection of vehicle or the cannabinoid receptor agonist WIN 55,212-2
      at doses of 0.1, 1.0 or 10 microg in 10 microl. Although the intrathecal
      application of WIN 55,212-2 did not alter nocifensive behavior following
      capsaicin, it produced a dose-dependent decrease in hyperalgesia to heat and
      mechanical stimuli. Intrathecal pretreatment with the CB1 receptor antagonist
      SR141716A (10 microg) blocked the antihyperalgesia produced by WIN 55,212-2. The
      ability of intrathecal administration of WIN 55,212-2 to attenuate hyperalgesia
      was not due to motor deficits since the highest dose of WIN 55,212-2 did not
      alter performance on the rota-rod test. To investigate whether cannabinoids
      attenuated capsaicin-evoked hyperalgesia through peripheral mechanisms, separate
      groups of rats were pretreated with an intraplantar injection of WIN 55,212-2 at
      doses of 0.1, 1.0, 10 or 30 microg in 100 microl 5 min before capsaicin.
      Intraplantar pretreatment with WIN 55,212-2 produced a dose-dependent attenuation
      of hyperalgesia to heat, but did not attenuate mechanical hyperalgesia or the
      duration of nocifensive behavior. The inactive enantiomer WIN 55,212-3 did not
      alter the development of hyperalgesia. SR141716A (100 microg) co-injected with
      WIN 55,212-2 (30 microg) partially attenuated the effects of WIN 55,212-2 on
      hyperalgesia to heat. Intraplantar injection of the highest dose of WIN 55,212-2
      did not interfere with the development of hyperalgesia following capsaicin
      injection into the contralateral paw. These data show that cannabinoids possess
      antihyperalgesic properties at doses that alone do not produce antinociception,
      and are capable of acting at both spinal and peripheral sites.

PMID- 11514091
TI  - Antigen binding characteristics of antibodies induced against nitric oxide
      modified plasmid DNA.
AB  - Nitric oxide (NO) generated by the reduction of sodium nitrite with sodium
      dithionite caused damage to plasmid Bluescript DNA leading to strand breaks and
      base modifications. The NO-plasmid DNA was highly immunogenic in rabbits. The
      antibody activity was inhibited to the extent of 86% with the immunogen as
      inhibitor, indicating the induction of immunogen specific antibodies. However,
      delineating the antigenic specificity of anti-NO-plasmid DNA antibodies by
      competition ELISA, multiple cross-reactivity was observed. The antibodies
      recognised B-, A- and allied conformations. The visual detection of immune
      complex formation with native and NO-plasmid DNA reiterated preferential binding
      with modified plasmid DNA. DNA modified by nitric oxide presents unique epitopes
      which may be one of the factors in antigen-driven autoimmune response in systemic
      lupus erythematosus.

PMID- 11514092
TI  - A novel disaccharide substrate having 1,2-oxazoline moiety for detection of
      transglycosylating activity of endoglycosidases.
AB  - A disaccharide substrate of Manbeta1-4GlcNAc-oxazoline 2 was designed and
      synthesized as a novel probe for detection of the transglycosylating activity of
      endoglycosidases. A regio- and stereoselective transglycosylation reaction of 2
      to GlcNAcbeta1-O-pNP or Dns-Asn(GlcNAc)-OH catalyzed by endo-beta-N
      acetylglucosaminidase from Mucor hiemalis (Endo-M) and endo-beta-N
      acetylglucosaminidase from Arthrobacter protophormiae (Endo-A) has been
      demonstrated for the first time, resulting in the core trisaccharide derivative
      Manbeta1-4GlcNAcbeta1-4GlcNAcbeta1-O-pNP 8 (or -(Dns)Asn-OH). Interestingly, the
      transglycosylation proceeds irreversibly; the resulting trisaccharide 8 was not
      hydrolyzed by Endo-M and Endo-A. Based on these results, a new mechanism
      including an oxazolinium ion intermediate has been proposed for the
      endoglycosidase-catalyzed hydrolysis or transglycosylation.

PMID- 11514093
TI  - MFAME, N-methyl-N-D-fructosyl amphotericin B methyl ester, a new amphotericin B
      derivative of low toxicity: relationship between self-association and effects on
      red blood cells.
AB  - In aqueous solutions N-methyl-N-D-fructosyl amphotericin B methyl ester (MFAME),
      a novel amphotericin B derivative with low animal toxicity, similar to its parent
      antibiotic, exists in three forms: monomeric, soluble and insoluble aggregates in
      equilibrium [1]. The aim of our work was to examine the influence of medium
      composition on the MFAME self-association and the relationship between MFAME self
      association and its toxicity towards red blood cells. The toxicity of MFAME in
      aggregated state towards red blood cells was tested by measuring the induction of
      potassium leakage and extent of haemolysis. The proportions of antibiotic species
      present in various aqueous media were determined by analysis of the UV-Vis
      spectra as a function of the antibiotic concentration. Numeric decomposition of
      the spectra allowed identification of four spectral species present in MFAME
      solutions: monomeric and three aggregated forms. Our results indicate that these
      aggregates, named type I, type II and type III, are different in terms of
      spectral properties, as well as effectiveness towards red blood cells. Soluble
      aggregate types I and III are the active forms of MFAME towards erythrocytes. The
      medium composition seems to be the main factor determining which type of
      antibiotic aggregate prevails in solution.

PMID- 11514094
TI  - Superoxide is responsible for apoptosis in rat vascular smooth muscle cells
      induced by alpha-tocopheryl hemisuccinate.
AB  - We investigated the mechanism of cell toxicity of alpha-tocopheryl hemisuccinate
      (TS). TS concentration- and time-dependently induced the lactate dehydrogenase
      release and DNA fragmentation of rat vascular smooth muscle cells (VSMC).
      Exogenous addition of superoxide dismutase, but not catalase, significantly
      inhibited the cell toxicity of TS. The NADPH-dependent oxidase activity of VSMC
      was stimulated by TS treatment. The cell toxicity of TS was inhibited by NADPH
      oxidase inhibitor 4-(2-aminoethyl)-benzenesulfonyl fluoride. Consequently, TS
      induced apoptosis of VSMC was suggested to be caused by exogenous O(2)(-)
      generated via the oxidase system activated with TS.

PMID- 11514095
TI  - Quantitative structure-activity relationships in enzymatic single-electron
      reduction of nitroaromatic explosives: implications for their cytotoxicity.
AB  - The mechanisms of cytotoxicity of polynitroaromatic explosives, an important
      group of environmental pollutants, remain insufficiently studied so far. We have
      found that the rate constants of single-electron enzymatic reduction, and the
      enthalpies of single-electron reduction of nitroaromatic compounds
      (DeltaHf(ArNO(2)(-*)), obtained by quantum mechanical calculation, may serve as
      useful tools for the analysis of cytotoxicity of nitroaromatic explosives with
      respect to the possible involvement of oxidative stress. The single-electron
      reduction rate constants of a number of explosives including 2,4,6
      trinitrotoluene (TNT) and 2,4,6-trinitrophenyl-N-methylnitramine (tetryl), and
      model nitroaromatic compounds by ferredoxin:NADP(+) reductase (FNR, EC 1.18.1.2)
      and NADPH:cytochrome P-450 reductase (P-450R, EC 1.6.2.4) increased with a
      decrease in DeltaHf(ArNO(2)(-*)). This indicates that the reduction rates are
      determined by the electron transfer energetics, but not by the particular
      structure of the explosives. The cytotoxicity of explosives to bovine leukemia
      virus-transformed lamb kidney fibroblasts (line FLK) increased with a
      corresponding increase in their reduction rate constant by P-450R and FNR, or
      with a decrease in their DeltaHf(ArNO(2)(-*)). This points to an importance of
      oxidative stress in the toxicity of explosives in this cell line, which was
      further evidenced by the protective effects of desferrioxamine and the
      antioxidant N,N'-diphenyl-p-phenylene diamine, and an increase in lipid
      peroxidation. DT-diaphorase (EC 1.6.99.2) exerted a minor and equivocal role in
      the cytotoxicity of explosives to FLK cells.

PMID- 11514096
TI  - Effect of tunicamycin on N-acetyl-beta-D-glucosaminidase produced by Trichoderma
      harzianum.
AB  - The effect of tunicamycin, an inhibitor of protein N-glycosylation, was studied
      in non-growing mycelium of Trichoderma harzianum induced to secrete N-acetyl-beta
      D-glucosaminidase by the addition of N-acetylglucosamine. Tunicamycin (30 microg
      ml(-1)) had no significant effect on growth of the fungus, or on the total
      protein secreted or specific activity of N-acetyl-beta-D-glucosaminidase.
      However, in the presence of the inhibitor an underglycosylated form of the enzyme
      was produced. The apparent molecular masses for this and the native enzyme were
      110 and 124 kDa, respectively. Both forms of the enzyme showed the same optimum
      pH and temperature, but the underglycosylated form was more sensitive to
      inactivation by both high temperature (60 degrees C) and the proteolytic enzyme
      trypsin.

PMID- 11514097
TI  - High affinity binding of the transcobalamin II-cobalamin complex and mRNA
      expression of haptocorrin by human mammary epithelial cells.
AB  - Little is known about the acquisition of cobalamin by the mammary gland and its
      secretion into milk. Human milk and plasma contain at least two types of
      cobalamin binding proteins: transcobalamin II (TC) and haptocorrin (HC). In
      plasma, TC is responsible for the transport of cobalamin to tissues and cells;
      however, cobalamin in milk is present exclusively bound to HC. We show that human
      mammary epithelial cells (HMEC) exhibit high affinity for TC; Scatchard analysis
      revealed a single class of binding sites for the TC-[(57)Co]cyanocobalamin
      complex with a dissociation constant (K(d)) of 4.9 x 10(-11) M. Uptake of the TC
      [(57)Co]cyanocobalamin complex at 37 degrees C was saturable by 24 h. Binding of
      free [(57)Co]cyanocobalamin to HMEC was not saturable and very limited binding of
      the HC-[(57)Co]cyanocobalamin complex was observed. Expression of the haptocorrin
      gene by HMEC was confirmed by Northern blot and PCR analysis. Thus, a specific
      cell surface receptor for the TC-cobalamin complex exists in the mammary gland
      and once cobalamin is internalized, it may be transferred to HC and subsequently
      secreted into milk as a HC-cobalamin complex.

PMID- 11514098
TI  - Quercetin modifies reactive oxygen levels but exerts only partial protection
      against oxidative stress within HL-60 cells.
AB  - Quercetin may contribute to the protection afforded by fruit- and vegetable-rich
      diets against diseases for which excess production of reactive oxygen species
      (ROS) has been implicated as a causal or contributory factor. We examine the
      effect of short term (90 min) quercetin (1-100 microM) exposure on the progress
      of menadione induced oxidative stress within HL-60 cells. 2',7'
      dichlorofluorescein and rhodamine-123 fluorescence, resulting from oxidation of
      the ROS-sensitive dyes dichlorodihydrofluorescein and dihydrorhodamine-123
      respectively, were utilised as indicators of general ROS levels. Ethidium
      fluorescence, resulting from oxidation of dihydroethidium, was used as a
      potentially more specific indicator of O(2)(-). Exposure to quercetin alone
      induced a decrease in DCF and rhodamine fluorescence. Conversely, ethidium
      fluorescence was enhanced by treatment with >or=40 microM quercetin. Incubation
      with 1-100 microM quercetin reduced the extent of menadione-induced increase in
      DCF and rhodamine fluorescence but the menadione-induced increase in ethidium
      fluorescence was further elevated for cells treated with >or=25 microM quercetin.
      Exposure to >or=10 microM quercetin abrogated menadione-induced DNA single-strand
      breaks but, paradoxically, quercetin exacerbated membrane damage and failed to
      enhance the viability of menadione-challenged cells. In conclusion, quercetin
      exerts only site-specific protection against oxidative stress.

PMID- 11514100
TI  - The effect of natural antioxidants, NAO and apocynin, on oxidative stress in the
      rat heart following LPS challenge.
AB  - Oxidative damage plays a key role in septic shock induced by lipopolysaccharide
      (LPS) which is known to enhance the formation of reactive oxygen species (ROS).
      In this study, biochemical parameters indicative of oxidative stress were tested
      in the rat heart following LPS challenge, with and without pretreatment with the
      antioxidants NAO (natural antioxidant) and apocynin. NAO is a natural antioxidant
      isolated and purified from spinach and its main components are flavonoids and
      coumaric acid derivatives. Treatment with LPS alone significantly (P<0.05)
      increased the malondialdehyde (MDA) level in heart, both in cytosolic and
      mitochondrial fractions by 1.5- and 2.4-fold, respectively, and in plasma (2.66
      fold). In the heart homogenate, the level of hydroperoxides also increased
      significantly (P<0.05). In addition, LPS treatment significantly (P<0.05)
      increased NADPH oxidase activity in the heart microsomal fraction by
      approximately 10-fold compared to control. Pretreatment for 7 days with either
      apocynin or NAO prior to the LPS challenge significantly (P<0.05) improved rat
      survival, decreased MDA levels in both fractions and decreased microsomal NADPH
      oxidase activity, compared to LPS alone. Catalase (CAT) activity slightly
      increased at 24 h post-LPS injection in LPS group and returned to the control
      level in the apocynin treated group. No meaningful changes were indicated for
      glutathione peroxidase activity among all the treatment groups. The activities of
      cytosolic and mitochondrial superoxide dismutase (SOD) enzymes significantly
      (P<0.05) increased approximately 20% in the LPS-treated group, compared to
      control. Apocynin significantly (P<0.05) decreased SOD level in the mitochondrial
      fraction with no effect on the cytosolic fraction; whereas, NAO had no important
      effect on SOD level in both fractions. The beneficial pretreatment effects of the
      antioxidants against oxidative stress in the rat heart presented in this study
      may suggest a potential chemopreventive effect of this compound in sepsis
      prevention.

PMID- 11514101
TI  - Suppression of Fas ligand expression on endothelial cells by arsenite through
      reactive oxygen species.
AB  - Chronic exposure to arsenite is associated with vascular disease, such as
      arteriosclerosis. However, the cellular mechanisms for vascular disease in
      response to arsenic are not well known. The present study has demonstrated that
      arsenite not arsenate decreased the Fas ligand (FasL) expression on ECV304 cells
      through reactive oxygen species. Incubation of ECV304 cells with arsenite
      decreased the FasL expression and increased the intracellular peroxide levels. In
      addition, hydrogen peroxide was found to suppress FasL expression in a dose
      dependent manner. The antioxidant, N-acetyl-cysteine, blocked the suppression of
      FasL expression in response to arsenite. These data suggested that arsenite
      initiates endothelium dysfunction, at least partly, by suppressing the FasL
      expression through activating reactive oxygen species sensitive endothelial cell
      signaling.

PMID- 11514102
TI  - Cigarette smoke-induced protein oxidation and proteolysis is exclusively caused
      by its tar phase: prevention by vitamin C.
AB  - We have reported before that whole phase cigarette smoke (CS) contains stable
      oxidants that cause oxidative damage and increased proteolysis of proteins [Free
      Radic. Biol. Med. 27 (1999) 1064]. Here, we demonstrate that these oxidants are
      exclusively present in the tar phase of the CS and not its gas phase and can
      almost wholly account for the observed whole phase CS-induced oxidation of human
      plasma proteins as well as extensive oxidative proteolysis of guinea pig lung and
      heart microsomal proteins in vitro. The mechanism of the tar phase CS-induced
      proteolysis of microsomal proteins involves two-steps: (i) initial oxidation of
      the proteins by oxidants present in the tar extract followed by (ii) rapid
      proteolytic degradation of the oxidized proteins by proteases present in the
      microsomes. Like the whole phase CS, the oxidative damage of proteins caused by
      the tar phase CS, as evidenced by the formation of protein carbonyl and
      bityrosine as well as loss of tryptophan residues and thiol groups, is also
      almost completely prevented by ascorbic acid and only partially by glutathione.
      Other antioxidants, including superoxide dismutase, catalase, vitamin E, beta
      carotene and mannitol are ineffective. This again leads us to suggest that
      adequate intake of vitamin C may help smokers to evade the CS-induced
      degenerative diseases associated with oxidative damage. The revelation of the
      acute toxicity of the tar phase with respect to CS-induced oxidative damage also
      urges the necessity of trapping it more effectively by suitable cigarette filters
      to reduce the health damage caused to smokers.

PMID- 11514103
TI  - Localization of glutamate-cysteine ligase mRNA and protein in mouse kidney and
      induction with methylmercury.
AB  - Methylmercury (MeHg) is a toxicant that targets the kidney among other tissues.
      MeHg accumulates in the kidney, where it indirectly produces oxidative stress due
      to glutathione depletion and leakage of reactive oxygen species from the
      mitochondria. Glutathione is believed to have an important role in protecting the
      kidney against MeHg toxicity, and MeHg exposure is known to result in the
      induction of GSH synthesis through the upregulation of the enzyme glutamate
      cysteine ligase (GLCL). GLCL, the rate-limiting enzyme in GSH synthesis, is
      composed of two subunits, a large catalytic (GLCLc) and a smaller regulatory
      (GLCLr) subunit. In this study we show that GLCLc and GLCLr mRNAs and GLCLc
      protein are localized in the paracortical region of the mouse kidney, the area of
      the kidney with the highest MeHg concentration, and that the upregulation of
      these mRNAs induced by MeHg is also located to the same region. This supports the
      role of GLCL in protection against MeHg toxicity in the kidney.

PMID- 11514104
TI  - Cocaine toxic effect on endothelium-dependent vasorelaxation: an in vitro study
      on rabbit aorta.
AB  - Effects of cocaine on vascular endothelium relaxing properties and the related
      mechanism were investigated in vitro in rabbit aorta. Several vasorelaxing agents
      with different mechanisms, i.e. acetylcholine, substance P, calcium ionophore
      A23187, 2,5-di-tert-butylhydroquinone, or sodium nitroprusside, were employed.
      Cocaine effects on the vascular response to relaxing agents in cumulative
      (acetylcholine, substance P, or A23187) or single dose (2,5-di-tert-butyl
      hydroquinone) were performed in endothelium-intact aortic rings precontracted
      with phenylephrine. Relaxing activity of cumulative doses of sodium nitroprusside
      was evaluated in endothelium-denuded aortic rings, in the presence of cocaine.
      Cocaine significantly reduced endothelium-dependent relaxations induced by
      acetylcholine, or substance P. By contrast A23187 endothelium-mediated relaxation
      as well as endothelium-independent relaxation by sodium nitroprusside were
      unaffected by cocaine. Furthermore, cocaine significantly increased endothelium
      dependent relaxation response to 2,5-di-tert-butylhydroquinone, a sarcoplasmic
      Ca2+-ATPase pump inhibitor, in the aortic rings. These findings indicate that
      cocaine reduces nitric oxide release from vascular endothelium apparently through
      the inhibiting action of Ca2+-ATPase pump.

PMID- 11514105
TI  - Combined exposure to sarin and pyridostigmine bromide increased levels of rat
      urinary 3-nitrotyrosine and 8-hydroxy-2'-deoxyguanosine, biomarkers of oxidative
      stress.
AB  - In this study concentrations of markers of oxidative stress 3-nitrotyrosine and 8
      hydroxy-2'-deoxyguanosine (8-OhdG) were determined in rat urine following a
      single oral dose of pyridostigmine bromide (PB) 13 mg/kg and a single
      intramuscular dose of sarin 80 microg/kg alone or in combination. Urine samples
      were collected 16, 24, 48, 72, and 96 h following dosing. Control urine samples
      of five rats treated with normal saline were also collected at the same time
      intervals. A combined dose of PB and sarin significantly increased levels of 3
      nitrotyrosine and (8-OhdG) starting 48 h after dosing. An increase in the
      concentration of these markers was not detected following a single dose of PB or
      sarin alone. Maximal increase in 3-nitrotyrosine and 8-OhdG was detected 48 h
      after administration of a combination PB and sarin. The results indicate that
      concurrent exposure to PB and sarin could generate free radical species that may
      cause oxidative stress in rats. The results may have significant impact if
      veterans were expose to sarin following an oral dose of PB.

PMID- 11514106
TI  - Comparison of CALUX-TEQ values with PCB and PCDD/F measurements in human serum of
      the Flanders Environmental and Health Study (FLEHS).
AB  - In 1999, a campaign of the Flemish Ministry of Health, Belgium was set up to
      assess pollutant concentrations and related health effect biomarkers in humans
      living in two regions of Flanders. The study was called the 'Flemish Environment
      and Health Study' (FLEHS). Concentrations of selected organochiorine pesticides,
      polychlorinated biphenyls (PCB) and polychlorinated dibenzo-p-dioxins (PCDD) and
      flirans (PCDF) were measured by gas chromatography-mass spectrometry in 47 pooled
      human serum samples originating from 200 individual women between 50 and 65 years
      living in two Flemish regions. The CALUX (Chemical-Activated Luciferase gene
      eXpression) bioassay was assessed on the same pools. The correlation between
      CALUX-TEQ and total TEQ (sum of PCDD/PCDF, non- and mono-ortho PCBs) varied from
      0.43 to 0.73 for the rural and urban region, respectively. The mean value for the
      total TBQ (75 pg WHO-TEQ/g fat) was two times higher than the mean TEQ value
      determined with the CALUX bioassay (36 pg TEQ/g fat). This shows that the
      assessment of dioxin-like exposure by these two measurements was different.
      However, regional differences in concentrations were observed for neither total
      TEQs, nor CALUX-TEQs. It was concluded that the CALUX can be an alternative
      screening tool for biomonitoring purposes, especially when the objective is to
      compare different groups of people (e.g. living in different regions).

PMID- 11514107
TI  - Effects of volatile and intravenous anesthetics on the uptake of GABA, glutamate
      and dopamine by their transporters heterologously expressed in COS cells and in
      rat brain synaptosomes.
AB  - Although the neurotransmitter uptake system is considered a possible target for
      the presynaptic action of anesthetic agents, observations are inconsistent
      concerning effects on the transporter and their clinical relevance. The present
      study examined the effects of volatile and intravenous anesthetics on the uptake
      of GABA, glutamate and dopamine in COS cells heterologously expressing the
      transporters for these neurotransmitters and in the rat brain synaptosomes.
      Halothane and isoflurane, but not thiamylal or thiopental, significantly
      inhibited uptake by COS cell systems of GABA, dopamine and glutamic acid in a
      concentration-dependent manner within clinically relevant ranges for anesthesia
      induced by these agents. Similarly, in synaptosomes halothane and isoflurane but
      not thiopental significantly suppressed the uptake of GABA and glutamic acid,
      respectively. These results do not support the hypothesis that volatile and
      intravenous anesthetics exert their action via specific inhibition of GABA uptake
      to enhance inhibitory GABAergic neuronal activity. Rather, they suggest that
      presynaptic uptake systems for various neurotransmitters including GABA may be
      the molecular targets for volatile anesthetic agents.

PMID- 11514109
TI  - Menopause, hormone replacement therapy and cancer.
AB  - OBJECTIVE: To comparatively review available evidence on hormone replacement
      therapy (HRT) and cancer. METHODS: Qualitative literature review. RESULTS: Most
      potential favorable and adverse effects on cancer risk of HRT are restricted to
      current users. On the basis of observational epidemiological data, the RR of
      breast cancer is moderately elevated in current and recent HRT users, and
      increases by about 2.3% per year with longer duration of use, but the effect
      drops after cessation and largely, if not totally, disappears after about 5
      years. Unopposed estrogen use is strongly related to endometrial cancer risk, but
      cyclic combined oestrogen-progestin treatment appears to largely or totally
      reduce this side effect, if progestin are used for at least 14 days per cycle.
      However, combined HRT may be associated with higher risk of breast cancer as
      compared to unopposed estrogens. HRT has been inversely related to colorectal
      cancer, although the issue of causal relation remains open to discussion. No
      consistent association was reported for ovarian, liver, other digestive or lung
      cancer. CONCLUSIONS: Recommendations for prolonged HRT use must be considered on
      an individual basis, taking into account the presence of other risk factors
      mainly for breast cancer, such as family history of breast cancer or a personal
      history of benign breast disease, as well as individual risk for other chronic
      diseases.

PMID- 11514108
TI  - Exposure to ozone aggravates nasal allergy-like symptoms in guinea pigs.
AB  - The ability of O3 exposure to aggravate ovalbumin (OVA)-induced nasal allergy
      like symptoms was studied in guinea pigs. Guinea pigs were exposed to filtered
      air or to 0.4 ppm O3 for 5 weeks. During the exposure, 1% OVA or saline was
      administered into the nasal cavities once a week. Sneezes and nasal secretions
      were measured for a 20-min period following OVA administration. The number of
      eosinophils infiltrating both nasal epithelium and subepithelium and titers of
      specific anti-OVA-IgG were measured 24 h after the last administration. Ozone
      increased OVA-induced sneezing and nasal secretion, as well as induced nasal
      hyper-responsiveness to physical stimuli. The number of eosinophils infiltrating
      the nasal subepithelium was increased by O3, and the titer of anti-OVA-IgG tended
      to increase in the O3-exposed animals. Thus, exposure to O3 aggravated nasal
      allergy-like symptoms by inducing nasal hyper-responsiveness, the infiltration of
      eosinophils, and by tending to increase the production of anti-OVA-IgG.

PMID- 11514110
TI  - The Kinmen women-health investigation (KIWI): a menopausal study of a population
      aged 40-54.
AB  - OBJECTIVES: This paper aims to report the methodology of a study of a cohort of
      middle-aged women in Taiwan, their age at menopause, and related factors and
      prevalence of menopausal symptoms, and to examine the relationships between
      symptoms and sociodemographic variables. METHODS: An epidemiological study of
      neuropsychological change during the menopausal transition among Chinese women
      aged 40-54 years old on the islet of Kinmen. RESULTS: Of a targeted population of
      2256 individuals, 1497 (66%) participated in the study. The mean age at menarche
      was 15.6 years and that at menopause was 48 years. The hormone use rate at the
      time of study was 23% in surgical menopausal women, and 9% were past users. After
      excluding surgical menopausal and premenopausal women, 6% reported a current use
      of estrogen replacement therapy and 6% were past users. The most frequently
      reported discomforts for those women aged >45 were troubled sleep, backaches, and
      joint pain. Four symptom clusters: musculoskeletal, non-specific somatic
      complaints, urogenital, and vasomotor, were identified. After adjustment for age,
      the urogenital and vasomotor symptoms were significantly associated with
      menopausal status. CONCLUSIONS: The age at menopause did not differ much from
      Western studies, but the menopausal symptoms, especially the vasomotor symptoms,
      were much lower in our study population. Nevertheless, vasomotor symptoms were
      still significantly associated with menopausal status.

PMID- 11514111
TI  - Prospective evaluation of body weight and body fat distribution in early
      postmenopausal women with and without hormonal replacement therapy.
AB  - AIMS: In order to assess the effects of menopause and hormonal replacement
      therapy (HRT) on body weight and body fat distribution (determined by dual energy
      X-ray), early postmenopausal women were given either oral calcium (500 mg/day,
      control group, n=13) or HRT, a combination of estradiol valerate (EV, 2 mg/day
      for 21 days) with cyproterone acetate (CPA, 1 mg/day in the last 10 days of the
      treatment cycle, n=18; Climen, Schering). RESULTS: There were no differences in
      basal body weight and body fat distribution in the two groups before the study.
      In control group, a significant (P<0.05) increase in body weight (from 63.5+/-2.0
      to 68.7+/-2.0 kg after 36 months) paralleled a shift to a prevalent central,
      android fat distribution with a slight but significant (P<0.05) increase in total
      body fat mass (from 23.4+/-2.1 to 29.1+/-2.1 kg), an increase in trunk (from
      10.1+/-0.4 to 12.7+/-0.4 kg, P<0.05), arms (from 2.4+/-0.2 to 2.9+/-0.2 kg,
      P<0.05) and legs (from 6.5+/-0.4 to 7.8+/-0.4 kg, P<0.05) fat. In the HRT group
      total body bone mineral showed a significant increase (from 1086+/-21 to 1128+/
      19 mg/cm(2), P<0.05) increase after 36 months, with no significant increase in
      body weight (from 62.6+/-1.8 to 65.0+/-1.9 kg), and no modifications in trunk
      (from 10.0+/-0.2 to 10.1+/-0.2 kg) and arms (from 2.4+/-0.1 to 2.6+/-0.1 kg) fat,
      but a significant increase in legs fat (from 6.9+/-0.3 to 9.9+/-0.4 kg, P<0.05).
      CONCLUSION: Present results demonstrate that menopause is associated with an
      accelerated increase in body weight and body fat, with a prevalent central,
      android fat distribution, that can be counteracted at least in part by oral HRT.

PMID- 11514112
TI  - Body composition characteristics are associated with the bone density of the
      proximal femur end in middle- and old-aged women and men.
AB  - OBJECTIVES: In the present study the associations between bone density of the
      proximal femur end and weight status, fat distribution patterns (FDI) and body
      composition parameters i.e. amount of body fat and lean body mass were tested in
      a sample of old aged women and men. METHODS: In 77 healthy women ranging in age
      from 60 to 92 years (x=71.8 years) and 62 healthy men ranging in age from 60 to
      86 years (x=71.5 years) the bone mineral density (BMD of the proximal femur end
      and the body composition parameters absolute fat mass, relative fat mass, lean
      body mass and bone mineral content were estimated by dual energy X-ray
      absorptiometry. Additionally, the weight status (body mass index, BMI) and the
      FDI were calculated. The bone density of the proximal femur end was correlated
      with the absolute fat mass and the lean body mass as well as with the BMI and the
      FDI. RESULTS: BMD correlated in females significantly positively with parameters
      of body composition, in males no significant correlations between fat mass
      (absolute and relative) and BMD as well as BMD/stature was found. Furthermore, it
      was shown that the weight status (BMI; r(2)=0.13, P<0.0003 in males and
      r(2)=0.27, P<0.000 in females), and the lean body mass (r(2)=0.21, P<0.001 in
      males, r(2)=0.36, P<0.004 in females) were associated significantly positively
      with the BMD of the proximal femur end in both sexes. The absolute fat mass had a
      significant impact on BMD in the female subsample only (r(2)=0.24, P<0.000).
      CONCLUSIONS: A lower weight status and a low amount of lean body mass, indicating
      not only lack of biomechanical forces of the proximal femur end, but also a lack
      of physical activity can be assumed to be associated increased bone loss and the
      development of osteoporosis in both sexes. An association between low amount of
      fat tissue and decreased BMD was especially found in women and may be due to the
      reduced conversion rates from androgens to estrogens in a low amount of fat
      tissue.

PMID- 11514113
TI  - Relationships of sex hormone levels to dependence in activities of daily living
      in the frail elderly.
AB  - OBJECTIVES: We undertook this nursing home study in order to determine the
      relationships between dependency in activities of daily living (ADL) and blood
      levels of estrone, testosterone, androstenedione, and dehydroepiandrosterone
      (DHEA). Little is known about this issue. METHODS: cross-sectional study of 370
      nursing home residents. Hormone levels in blood specimens drawn in 1997 and 1998
      were correlated with degree of ADL dependency recorded in medical charts.
      RESULTS: Because of multiple comparisons associations were deemed significant for
      P-values < or =0.017 for males and < or =0.0125 for females. In males, the
      following were inversely related: testosterone levels with dependency in
      transferring and eating; estrone with eating and a summary ADL index; and
      androstenedione with toileting and a summary ADL index (in all cases, r=-0.4;
      P=0.007-0.015). Inverse trends existed between testosterone levels and dependency
      in mobility and a summary ADL index; and androstenedione and eating (in all cases
      r=-0.3; P=0.030-0.055). Among females the following were directly related:
      estrone levels with dependence in mobility, toileting, transferring, and a
      summary ADL index; and DHEA with transferring and a summary ADL index (r=0.2-0.3,
      P=0.0001-0.01). Trends existed between estrone and eating, and DHEA and toileting
      (r=0.1-0.2, P=0.04). CONCLUSION: In male residents, higher sex hormone levels are
      associated with better ADL performance. Among females the opposite is true. While
      further studies are needed to elucidate these relationships, our results and
      recent findings of others suggest sex hormone actions in older women differ from
      those in younger populations. A possible stress-related mechanism is also
      presented.

PMID- 11514114
TI  - Homocysteine and folate levels in postmenopausal women.
AB  - OBJECTIVES: To assess total homocysteine (tHcy) and folate levels in
      postmenopausal women and investigate whether age, menopause duration, kind of
      menopause and tobacco use had an effect on these levels. METHODS: Total
      homocysteine and folate levels were measured in fasting blood samples of 200
      postmenopausal women with normal thyroid and renal function tests. Patients were
      not receiving vitamins or hormone replacement therapy. RESULTS: Total
      homocysteine levels increased significantly after 60 years while folate levels
      showed a decrease trend after 65 years. Menopause duration had no effect on
      folate levels and increased significantly tHcy levels after >180 months duration.
      The kind of menopause did not influence tHcy and folate levels. Tobacco use
      reduced significantly folate levels. CONCLUSIONS: Age seems to be the principal
      factor influencing tHcy levels. We believe that decreased folate levels also
      reflect an age-associated inadequate dietary intake. Tobacco use did not alter
      tHcy levels; however, we found smoking to lower folate levels.

PMID- 11514115
TI  - Attitudes to menopause and hormone replacement therapy among Asian and Caucasian
      women general practitioners.
AB  - OBJECTIVE: To look for any differences in attitudes to menopause and hormone
      replacement therapy (HRT) between Asian and Caucasian women standardised for
      educational background, socio-economic status and access to medical information.
      METHOD: Self administered postal questionnaire sent to 144 women doctors (general
      practitioners) in defined geographical areas. RESULTS: The overall response rate
      was 61%. Both Asian and Caucasian women responded in a similar manner for most
      aspects. A high proportion of these women doctors (over 75%) would seek HRT at
      the climacteric. More Asian respondents reported a fear of breast cancer
      (P=0.001), and that a woman feels less of a woman after the menopause (P=0.02).
      More Caucasian respondents felt positively about the potential for HRT to enhance
      enjoyment of life (P=0.01). CONCLUSIONS: The lack of major differences between
      the ethnic groups in our sample suggests that variations reported elsewhere may
      be due to lack of knowledge and/or differences in socio-economic status.

PMID- 11514116
TI  - A study of the psychological status and sexuality in middle-aged Bulgarian women:
      significance of the hormone replacement therapy (HRT).
AB  - OBJECTIVE: The psychoemotional and sexual status of Bulgarian urban
      postmenopausal women 10 years after the beginning of the period of extensive
      political, social, economic and cultural transitions was studied. SUBJECTS AND
      METHODS: Three hundred and thirty-two postmenopausal women (83.5% in natural
      menopause and 16.5% in surgical menopause) and 295 women with normal menstrual
      cycle in several Bulgarian cities and the capital were studied. A campaign for
      free-of-charge bone density measurement was announced and the examined subjects
      filled in an individual anonymous questionnaire. SPSS for Windows version 8.0 was
      used for the statistical processing of the results. The comparison was made
      between normally menstruating women (n=295), postmenopausal women on hormone
      replacement therapy (HRT) (n=36) and postmenopausal subjects without HRT (n=296).
      RESULTS: A significant correlation was observed between depression and sexual
      aversion, depression and pain with intercourse, depression and the change in the
      sexual life after menopause. The correlation between self-esteem and sexual
      thoughts, self-esteem and sexual desire, self-esteem and the arousal from the
      partner, self-esteem and orgasm also proved important. About 20% of the studied
      subjects reported depressive thoughts, 50% reported anxiety and the self-esteem
      was very low in 13%. These results can be explained in part with the economic
      stagnation in the country, the unemployment and uncertainty. However, 94% of
      Bulgarian women believe that they do well in life and rely on their
      professionalism and social positions. All parameters of sexual life are
      significantly lower in the postmenopausal group without HRT as compared both with
      menstruating women and postmenopausal women on HRT. Marital status influences
      them too. CONCLUSION: The change in the sexuality is related to the decline in
      the estrogen activity, the influence of the psychosocial factors, the lack of a
      permanent intimate partner, and the derogatory attitude of the society towards
      the sexuality of postmenopausal women.

PMID- 11514117
TI  - Evaluation of combining kava extract with hormone replacement therapy in the
      treatment of postmenopausal anxiety.
AB  - OBJECTIVE: to evaluate the efficacy of combining kava extract with hormone
      replacement therapy in the treatment of menopausal anxiety. MATERIALS AND
      METHODS: HAMA score was evaluated before and after therapy in four groups of
      women in menopause (duration of menopause ranged from 1 to 12 years). The groups
      were treated with hormone replacement therapy (with and without progestogens) and
      kava extract or placebo for 6 months. RESULTS: A significant reduction in HAMA
      score was observed in all four groups of women. The reduction was more
      significant in groups taking kava extract than in groups on hormones only.
      DISCUSSION: The combined use of hormone replacement therapy and kava extract
      seems to be effective against menopausal anxiety. Kava extract accelerates
      resolution of psychological symptoms while hormone therapy safeguards against
      osteoporosis and cardiovascular disease.

PMID- 11514118
TI  - Role of active oxygen species and antioxidants in photoaging.
AB  - The mechanism for the formation of active oxygen species and their reactions with
      antioxidants is described. The importance of the free radical chain oxidation and
      the singlet oxygen-dependent oxidation is suggested by a decrease in skin levels
      of alpha-tocopherol, ubiquinol-10, and ascorbic acid with a concomitant formation
      of lipid hydroperoxides during UV irradiation of murine skin, and the formation
      of squalene hydroperoxides in human skin upon UV exposure, respectively.

PMID- 11514119
TI  - Mechanical methods for evaluating skin surface architecture in relation to
      wrinkling.
AB  - Various methods have recently been developed to study skin surface micro
      structures including wrinkles and these techniques have been frequently modified
      in the search for an appropriate and ideal method. This article reviews a number
      of earlier reported techniques including profilometric, two-dimensional, scanning
      electron microscopic, confocal microscopic, and three-dimensional methods. This
      review also reports some experimental results related to image analysis as a two
      dimensional method and to light cutting analysis as a three-dimensional method.
      We also discuss problems and limitations of the two-dimensional methods, the
      techniques used to replicate skin surface micro-architecture, and the in vivo
      measurements.

PMID- 11514120
TI  - Pentosidine in advanced glycation end-products (AGEs) during UVA irradiation
      generates active oxygen species and impairs human dermal fibroblasts.
AB  - Our previous study reported that advanced glycation end-products (AGE)-modified
      BSA produced active oxygen species, *O2-, H2O2, and *OH under UVA irradiation and
      enhanced the cytotoxicity of UVA light. We examined whether pentosidine in AGE
      modified BSA was involved in one of the mechanisms generating the active oxygen
      species. In biological investigations, fibroblasts exposed to UVA (20 J/cm2) in
      the presence of pentosidine-rich compounds (PRCs), which were prepared with L
      arginine, L-lysine and glucose, showed a time-dependent leakage of the cytosolic
      enzyme LDH. In addition, release of LDH was suppressed by addition of DMSO and
      deferoxamine under UVA irradiation. From these results, it was determined that
      PRCs exposed to UVA damaged the plasma membrane of human dermal fibroblasts due
      to the conversion of *OH from H2O2 via a Fenton-like reaction. These features of
      PRCs exposed to UVA were consistent with those of AGE-modified BSA. In an ESR
      study, PRCs under UVA irradiation yielded DMPO-OH (DMPO-OH adduct) using DMPO as
      a spin-trapping reagent. *O2- generation from UVA-irradiated PRCs was also
      indicated by the combination of NBT reduction and SOD. When PRCs were exposed to
      UVA light controlled with a long-pass filter, WG-360, it was found that their
      production of *O2- was prohibited less than 50% in the NBT reduction assay. The
      *O2- production profile of PRCs depending on the wavelength of UVA light was
      similar to that of AGE-modified BSA. Furthermore, it was found that the H2O2
      level was increased by PRCs exposed to UVA. These results indicated that
      pentosidine is an important factor of AGE-modified BSA in active oxygen
      generation under UVA irradiation.

PMID- 11514121
TI  - Epidermal changes caused by chronic low-dose UV irradiation induce wrinkle
      formation in hairless mouse.
AB  - To investigate the effects of chronic low-dose UV irradiation on the skin,
      hairless mice were irradiated with a 1/3 minimal erythemal dose (MED) of UV. We
      examined the relationship between visible changes and skin damage in the dermis
      and epidermis. Hairless mice were irradiated with UVB (20 mJ/cm2) and UVA (14
      J/cm2) three times a week for 10 weeks, followed by a 24-week non-irradiation
      period. Visible fine wrinkling was present after 4 weeks of irradiation, and the
      wrinkling progressively worsened throughout the period of irradiation. The
      wrinkles remained after irradiation was discontinued. In dermal components, no
      significant histological changes in the collagen fibers and elastic fibers were
      found, and the amount of hydroxyproline was also not changed. Thus, in the
      epidermis, there was a significant increase in the number of stratum corneum
      layers and the terminal-differentiation marker, filaggrin, positive cells. The
      intensity of staining for the differentiation marker, keratin 1, was reduced.
      These changes were accompanied by wrinkle formation, and remained after
      discontinuance of irradiation. These findings suggested that chronic low-dose UV
      irradiation induces structural and quantitative changes in the epidermis as a
      result of keratinization impairment, and that this damage in the epidermis is an
      important causative factor in wrinkle formation.

PMID- 11514122
TI  - Skin premature aging induced by tobacco smoking: the objective evidence of skin
      replica analysis.
AB  - Epidemiological studies have showed that heavy smoking causes premature skin
      aging. Using a silicone rubber replica combined with computerized image
      processing, an objective measurement of skin's topography, we investigated the
      association between wrinkle formation and tobacco smoking in this study. The
      replica analysis was used to study the changes in the surface furrows of the
      volar forearm in 63 volunteers. Results confirmed that the depth (Rz) and
      variance (Rv) of furrows were increased and lines of furrows (Rl) were decreased
      with age. The replica analytic results showed that Rz and Rv in subjects with a
      smoking history > or =35 pack-years were significantly higher than non-smokers
      (P<0.05). Rl in subjects with a smoking history were significantly lower than non
      smokers (P<0.05). In addition, the present results gave a good correlation
      between the parameters from the computerized replica analysis with the clinical
      grading assessment of wrinkles, which further confirmed that skin replica
      technique is an objective and efficacious tool in evaluation of skin premature
      aging.

PMID- 11514124
TI  - Quantitative evaluation of skin condition in an epidemiological survey of females
      living in northern versus southern Japan.
AB  - Image analysis and biophysical methods were used to compare the skin condition of
      a group of females ranging in age from 5 to 65 years who had lived all of their
      lives in either Kagoshima (n=300), located in southern Japan, or Akita (n=302),
      located in northern Japan. Kagoshima annually receives approximately 1.5 times
      more solar UVB radiation than Akita. The methods used and corresponding skin
      parameters reported in this survey were: high resolution digital imaging followed
      by computer analysis of facial images for facial skin wrinkling and
      hyperpigmentation; silicone skin replicas followed by Moire interferometry for
      facial skin surface roughness (texture); the Minolta Chromameter for skin color
      (L*a*b*) on sun-exposed (forehead) and sun-protected (upper inner arm) skin
      sites; the Corneometer for skin capacitance (hydration) on the cheek and ventral
      forearm; the Sebumeter for sebum excretion rate on the forehead; and the Minolta
      Spot Thermometer for skin temperature on the upper cheek. Compared with Japanese
      women living in Akita, Japanese women living in Kagoshima had significantly
      longer facial wrinkles, higher number of wrinkles, larger hyperpigmented spots,
      higher number of spots, rougher facial skin texture, more yellow foreheads and
      upper inner arms, darker foreheads, and less stratum corneum hydration in the
      cheeks and arms. When compared on an age-for-age basis, the average 40-year-old
      Kagoshima women has the same level of facial wrinkling as a 48-year-old Akita
      women, a delay of 8 years for living in the northern latitude. For facial
      hyperpigmentation, the delay is 16 years; the average 40-year-old Kagoshima women
      has the same level of facial hyperpigmentation as a 56-year-old Akita women. The
      results further testify to the skin damaging effects of sun exposure and may be
      useful in public health education to promote everyday sun protection.

PMID- 11514123
TI  - Ultrastructural characterization of microvasculature in photoaging.
AB  - The cutaneous microvasculature was examined by electron microscopy in order to
      compare its characteristics in photodamaged preauricular skin and in sun
      protected postauricular sites of 15 Japanese women aged 58-81 years. The
      characteristic ultrastructural features of the microvasculature in photodamaged
      skin compared with those in sun-protected skin included dilated vessels embedded
      in elastin which depressed endothelial cells, vessels surrounded by a thick
      amorphous material composed of multiple laminations of a basement membrane-like
      material, and activated endothelial cells which had increased numbers of
      cytoplasmic organelles and pinocytotic vesicles. A novel finding of this study in
      photodamaged vessels was an increased formation of new vessels (angiogenesis) via
      two distinct pathways. In severe elastosis, activated endothelial cells with
      densely packed intracytoplasmic microfilaments extended large pseudopods into the
      elastotic material. In contrast, isolated mesenchymal cells, which possessed
      immature Weibel-Palade bodies, were scattered around pre-existing vessels within
      the Grenz zone. In some cases, many mesenchymal cells with electron-lucent
      cytoplasms aggregated and interconnected by cytoplasmic processes, which was
      followed by the formation of vascular structures. These results suggest that
      there are significant ultrastructural differences in vessels between photoaged
      and intrinsically aged facial skin and that the photodamaged microvascular system
      is characterized by the co-existence of regressive changes and angiogenesis.

PMID- 11514125
TI  - The efficacy of glycolic acid for treating wrinkles: analysis using newly
      developed facial imaging systems equipped with fluorescent illumination.
AB  - The clinical characteristics of photodamaged skin, such as coarse and fine
      wrinkling, can not be quantitatively evaluated from ordinary photographic
      records. The purpose of this study was to assess the efficacy of glycolic acid
      (GA) peeling on facial wrinkling, using computer assisted image analysis. This
      was accomplished with reproducible imaging techniques, which allowed precise
      repositioning of the subject's face in front of the camera. Two parameters, the
      change in wrinkle number and the change in wrinkle length were assessed. Although
      the clinical improvement of wrinkles correlated with both parameters, wrinkle
      length more precisely reflected the degree of clinical wrinkles, because the
      wrinkle number appeared to increase as some shallow wrinkles divided into
      multiple smaller wrinkles during their improvement. Comparison of responses by
      different age groups showed that the reduction of total wrinkle length was
      observed in the order of: 50s>30s and 40s>60s>over 70>under 30. The lack of
      response by subjects over 70 might be due to the nature of their wrinkles being
      mainly coarse wrinkles rather than fine ones. We next compared the effect of GA
      by concentration (35, 50 or 70%), but found no significant differences. As the
      concentration of GA used for treatment was determined by each subject's erythema
      reaction, our present result suggests that erythema elicited by GA correlates
      with improvement of wrinkles and that these two phenomena can be induced by a
      common pathway of GA treatment. This quantitative analysis clearly shows the
      efficacy and limitation of GA treatment of wrinkles, and might help to disclose
      the precise mechanisms of GA effects on the skin structure and function.

PMID- 11514126
TI  - New formulation of chemical peeling agent: histological evaluation in sun-damaged
      skin model in hairless mice.
AB  - BACKGROUND: chemical peelings injure the superficial skin, which is then restored
      by healing of the wound. OBJECTIVES: to document the acute and chronic
      histological changes produced by applying chemical peeling agents used clinically
      to the UVB-irradiated skin of hairless mice, which served as a model of sun
      damaged skin. DESIGN: three chemical peeling agents, 30% salicylic acid,
      dissolved in macrogol (a new formulation), 35% trichloroacetic acid (TCA)
      dissolved in distilled water and 20% glycolic acid dissolved in glycerin were
      applied to the backs of UVB-irradiated hairless mice. Untreated, irradiated areas
      of skin served as controls. Specimens were evaluated histologically at 3, 14, 28,
      and 70 days. RESULTS: chronic UVB irradiation produced an irregular hypertrophy
      of the epidermis. The treated areas of irradiated skin recovered by day 70. At 28
      days, all skin specimens treated with chemical peeling agents exhibited a unique
      connective tissue layer composed of fine collagen fibers beneath the epidermis.
      While 35% TCA produced severe tissue damage marked by inflammation up to day 14,
      no inflammatory infiltrates were seen with 30% salicylic acid in macrogol at 70
      days. CONCLUSIONS: chemical peeling with 30% salicylic acid dissolved in macrogol
      led to reorganization of the epidermis and a rebuilding of the superficial dermal
      connective tissue important in reducing wrinkles, and without evidence of
      inflammatory infiltrates in an animal model of sun-damaged skin. Findings suggest
      a possible clinical benefit.

PMID- 11514127
TI  - Effects of all-trans retinoic acid on melanogenesis in pigmented skin equivalents
      and monolayer culture of melanocytes.
AB  - The effects of all-trans retinoic acid (RA) on melanogenesis and the mechanism of
      its action in topical treatment have not been elucidated. The purpose of this
      study was to determine the effects of RA on melanogenesis in the pigmented skin
      equivalent as well as in monolayer culture of melanocytes, and to determine
      whether RA, hydroquinone (HQ), and hydrocortisone (HC) show synergistic
      depigmenting effects in combined treatments of each other. The suppressing effect
      of RA on melanogenesis was not observed in pigmented skin equivalents and
      monolayer culture of murine and human melanocytes, although HQ showed strong
      inhibition of melanogenesis. The synergistic effects between RA, HQ, and HC were
      not particularly seen. The results suggested that RA neither has direct
      inhibitory effects on melanogenesis of melanocytes, nor influences the cell-cell
      interactions between melanocytes, keratinocytes and fibroblasts, such as
      paracrine actions with regard to melanin production. The role of RA in bleaching
      treatments appears to be in other specific actions, such as promotion of
      keratinocytes proliferation and acceleration of epidermal turnover.

PMID- 11514128
TI  - Hierarchical arrangement of psychiatric symptoms in the context of schizophrenia.
AB  - Foulds' model proposing a four-class hierarchical structure of mental illness
      represents an interesting dimension of psychiatric research and discussion and
      probably has a significant potential on diagnosis, taxonomy, therapeutics and
      theory. Psychiatric symptoms were investigated in a group of 244 schizophrenic
      patients with the purpose of analyzing Foulds and Bedford's notion that
      psychiatric symptoms are arranged hierarchically. To achieve this the R (recent)
      version of the Delusions, Symptoms, States, Inventory (DSSI) was administered in
      the form of a constructed interview to these patients. The hierarchical
      arrangement of psychiatric symptoms was verified since a great majority of the
      cases (80.8%) produced symptom patterns conforming to the hierarchy model.
      However, patients with duration of illness longer than 10 years reported
      conforming patterns in a lower percentage (77%), whereas 84.6% of those with a
      duration of illness less than 2 years reported conforming patterns. The non
      conforming patterns were those in which integrated delusions were absent in the
      presence of delusions of disintegration, neurotic symptoms were absent in the
      presence of integrated delusions, and dysthymic states were absent in the
      presence of neurotic symptoms.

PMID- 11514129
TI  - Co-morbidity of personality disorders in individuals with substance use
      disorders.
AB  - This review summarizes the recent literature about personality disorders among
      substance abusers. First, it will be shown that personality disorders are highly
      prevalent co-morbid conditions among addicted individuals. Second, it is argued
      that this co-morbidity is likely to be accounted for by multiple complex
      etiological relationships. Finally, the clinical relevance of routine assessment
      of (maladaptive) personality traits in individuals admitting for substance abuse
      treatment will be discussed.

PMID- 11514130
TI  - Psychopathological predictors of suicide in patients with major depression during
      a 5-year follow-up.
AB  - OBJECTIVE: It is widely known that the risk of suicide is higher in cases of
      major depressive disorders in comparison to the general population. The purpose
      of this study was to examine which psychopathologic symptoms during the index
      episode are predictors for an increased risk of suicide in the further course of
      major depression. METHOD: Mortality data were determined from a prospective study
      of 280 patients with major depression (DSM-III-R, single episode or recurrent)
      during a follow-up period of 5 years. The predictive power of different
      depressive symptoms including psychotic symptoms for suicide risk was
      investigated. RESULTS: Patients who committed suicide (N = 16) during the follow
      up period had reported significantly more often hypochondriacal preoccupations or
      delusions (but not delusions or preoccupations of impoverishment, guilt or sin),
      suicidal thoughts and suicide attempts as well as feelings of severe hopelessness
      during the index episode than still living patients or patients who had died from
      natural causes. CONCLUSION: These symptoms seem to be helpful early predictors
      for the risk of suicide during the further course of illness. This should be
      taken into account for suicide prevention in the course of major depression.

PMID- 11514131
TI  - Bipolar sensation seeking is associated with a propensity to abuse rather than to
      temperamental characteristics.
AB  - OBJECTIVE: As some temperament profiles may be markers of genetic vulnerability
      traits, we aimed to compare sensation seeking in euthymic bipolar patients and in
      controls. METHODS: One hundred ninety-four patients fulfilling DSM-IV diagnostic
      criteria for bipolar disorders (BP), 81% of whom presented type I BP, and 95
      controls were included in this study. Euthymia was assessed using both the MADRS
      and Bech mania scales. Subjects were evaluated using the French abbreviated form
      of Zuckerman's Sensation Seeking Scale (SSS), which provide a total score (TS)
      and four subscores: Thrill and Adventure Seeking (TAS), Experience Seeking (ES),
      Disinhibition (Dis), and Boredom Susceptibility (BS). RESULTS: SSS total score
      differed significantly between men (17.2 +/- 0.5) and women (15.3 +/- 0.6) (P =
      0.02) and all the subscores were negatively correlated with age. On adjustment
      for sex and age, we found that bipolar patients had a high Dis score (P = 0.003).
      However, if the same analysis was performed with a lifetime history of alcohol
      abuse or dependence as a covariable, no such difference was found (P = 0.436).
      The SSS demonstrated a high degree of test-retest reliability (ICC = 0.91).
      CONCLUSION: These results suggest that sensation seeking assessed with the SSS is
      not a temperament characteristic associated with bipolar disorders but is instead
      linked to a tendency towards alcohol abuse.

PMID- 11514132
TI  - Predictors of compliance with neuroleptic medication among inpatients with
      schizophrenia: a discriminant function analysis.
AB  - OBJECTIVE: To identify clinically useful predictors of adherence to medication
      among persons with schizophrenia. METHOD: We evaluated levels of compliance with
      neuroleptic medication among 32 consecutive admissions with DSM-III-R
      schizophrenia from a geographically defined catchment area using a compliance
      interview. We also assessed symptomatology, insight, neurological status and
      memory. RESULTS: Less than 25% of consecutive admissions reported being fully
      compliant. Drug attitudes were the best predictor of regular compliance,
      symptomatology the best predictor of noncompliance, and memory the best predictor
      of partial compliance with neuroleptic medication. CONCLUSIONS: These data
      emphasise the complexity of factors that influence whether a person adheres to
      his medication regimen. Furthermore, they suggest that these factors may vary
      within the same person over time.

PMID- 11514133
TI  - Perceptions of the real and the ideal ward atmosphere among trainees and staff
      before and after the introduction of a new work rehabilitation model.
AB  - Changes in the ward atmosphere of a psychiatric work rehabilitation unit were
      investigated. Both trainees and staff filled in the Community-Oriented Programs
      Environment Scale (COPES) before and after a new rehabilitation model was
      implemented. It was hypothesised that the levels of autonomy and practical
      orientation would increase from both the trainees' and staff's perspective
      concerning the real ward atmosphere and that the staff's perceptions of an ideal
      ward atmosphere would change in the same way. The staff perceived an increased
      level of autonomy with respect to both the real ward atmosphere and to what
      constitutes an ideal ward atmosphere, which partly confirmed the hypotheses, but
      the level of practical orientation was stable. Concerning the staff's estimate of
      an ideal ward atmosphere, further changes were an increased level of involvement
      and a decrease in spontaneity, which was not hypothesised, but was not in
      conflict with the philosophy behind the new model. From the trainee's perspective
      there was no change of either autonomy or practical orientation. Instead, there
      was a decrease in personal problem orientation. Compared to an optimal profile,
      the ward atmosphere was beneficial, before as well as after implementation of the
      new programme. Differences were found between the staff and the trainees, but
      they were not large enough to separate the groups according to what is considered
      an optimal profile. The few changes found support earlier conclusions that the
      ward atmosphere is a stable phenomenon over time.

PMID- 11514134
TI  - The health economic implications of treatment with quetiapine: an audit of long
      term treatment for patients with chronic schizophrenia.
AB  - This retrospective, case series audit assessed the clinical and health-economic
      impact of long-term treatment with quetiapine ('Seroquel'), a new atypical
      antipsychotic, in patients with chronic schizophrenia. The study design was of a
      case series format, comprising patients entered from one centre into the open
      label extension of a multicentre 6-week efficacy study. Twenty-one patients (15
      male, six female; mean age 39 years) were studied, of whom 17 (81%) had been
      rated as 'partially responsive' to previous antipsychotics. Data on
      hospitalisations and information on symptoms were collected retrospectively for
      the 12 months before quetiapine treatment was initiated and for the 12 months
      after. Quetiapine was effective in reducing psychotic symptoms with mean BPRS
      scores reducing significantly, from 38 to 21 (P < 0.005). Motor function was also
      significantly improved with mean Simpson scale scores reducing from 15 to 12 (P <
      0.005). Average inpatient days were reduced by 11% in year two (97 compared with
      109 days) while the overall costs of treatment, including drug costs, fell by 5%
      (I pound sterling 20,843 to I pound sterling 19,827). Four patients had been
      hospitalised for longer than 5 years before starting quetiapine; these
      chronically institutionalised patients remained in hospital, despite improved
      clinical outcomes (mean BPRS scores after treatment of 34, compared with 43
      before), for the full 12 months of quetiapine treatment. Were the data from this
      audit to be re-analysed excluding these four patients then average inpatient days
      would have been reduced by 33% (45 to 30 days) and overall cost of treatment by
      19% (I pound sterling 8617 to I pound sterling 7011). This audit suggests that
      treatment with quetiapine over this 1-year period was associated with both
      clinical improvements and a decreased usage of inpatient services. The reduction
      in hospitalisation costs would appear to compensate for the increased cost of
      drug treatment. Significantly, potential savings appear to be greatest for those
      patients with a 'revolving door' pattern of repeated readmission.

PMID- 11514135
TI  - Gender and activation level in smokers.
AB  - Studies on the enhancing effects of nicotine on performance are usually
      pharmacological challenges using deprived male smokers. However, gender may be a
      factor that influences nicotine/smoking effects upon information processing. We
      investigated gender differences in contingent negative variation (CNV) amplitude
      in non-deprived dependent smokers performing a go-no go reaction time paradigm.
      Female smokers did not differ from female non-smokers in both early and late CNV,
      whereas male smokers presented greater early and late CNV compared to male non
      smokers and an alteration in inhibiting processes responsible for CNV development
      in the no go condition. Consistent with the evidence of gender differences in
      nicotine/smoking sensitivity, these preliminary results emphasize the need for
      taking into account gender in psychophysiological research of nicotine/smoking
      effects.

PMID- 11514136
TI  - Differences in interleukins' patterns between dysthymia and major depression.
AB  - We assessed whether cytokine production-interleukin (IL)-1beta, IL-6 and tumour
      necrosis factor-alpha (TNFalpha)-is affected in depressed patients, dysthymia
      (Dt) and major depression (MD), and its association with various parameters of
      severity and clinical course. We found a possible different pattern of
      interleukin production between Dt and MD.

PMID- 11514137
TI  - Nefazodone may inhibit the metabolism of carbamazepine: three case reports.

PMID- 11514138
TI  - Parallel solid-phase synthesis of nucleoside phosphoramidate libraries.
AB  - Combinatorial chemistry is playing an increasingly prominent role in the process
      of drug discovery. A nucleic acid-based (NAB) scaffold can be engineered to
      create functional group and topological diversity in a library. Described herein
      is the parallel solid-phase synthesis of combinatorial libraries of nucleoside
      phosphoramidates, and the first evaluation of antiviral activity against
      hepatitis B virus (HBV).

PMID- 11514139
TI  - 1,4-Disubstituted imidazoles are potential antibacterial agents functioning as
      inhibitors of enoyl acyl carrier protein reductase (FabI).
AB  - 1,4-Disubstituted imidazole inhibitors of Staphylococcus aureus and Escherichia
      coli enoyl acyl carrier protein reductase (FabI) have been identified. Crystal
      structure data shows the inhibitor 1 bound in the enzyme active site of E. coli
      FabI.

PMID- 11514140
TI  - Structure-activity study and analgesic efficacy of amino acid derivatives as N
      type calcium channel blockers.
AB  - The synthesis and structure-activity relationship (SAR) study of a novel series
      of N-type calcium channel blockers are described. L-Cysteine derivative 2a was
      found to be a potent and selective N-type calcium channel blocker with IC(50)
      0.63 microM on IMR-32 assay. Compound 2a showed analgesic efficacy in the rat
      formalin-induced pain model by intrathecal and oral administration.

PMID- 11514141
TI  - Pyridopyrimidine analogues as novel adenosine kinase inhibitors.
AB  - A novel series of pyridopyrimidine analogues 9 was identified as potent adenosine
      kinase inhibitors based on the SAR and computational studies. Substitution of the
      C7 position of the pyridopyrimidino core with C2' substituted pyridino moiety
      increased the in vivo potency and enhanced oral bioavailability of these
      adenosine kinase inhibitors.

PMID- 11514142
TI  - Synthesis, antimalarial activity and inhibition of haem detoxification of novel
      bisquinolines.
AB  - The synthesis of novel bisquinoline compounds comprising 4-(4-diethylamino-1
      methylbutyl)aminoquinoline units joined through the 2-position by a (CH(2))(n)
      linker is described. Their ability to inhibit the growth of both chloroquine
      sensitive (D10) and chloroquine-resistant (K1) strains of Plasmodium falciparum,
      the hydrogen peroxide-mediated pathway for decomposition of haem, and the
      conversion of haem to beta-haematin have been measured. The activity was affected
      by the length of the linker and the most active (6c, n=12) showed effects similar
      to chloroquine in three of the assays. However, it was even more active against
      the resistant strain [IC(50), 17 nM (K1); 43 nM (D10)], much superior to
      chloroquine (IC(50), 540 nM) and slightly better than mefloquine (IC(50), 30 nM)
      in this regard.

PMID- 11514143
TI  - Sar studies of piperidine-based analogues of cocaine. Part 3: oxadiazoles.
AB  - The synthesis of novel 4beta-aryl-1-methyl-3alpha-(3-substituted-1,2,4-oxadiazol
      5-yl)piperidines, bioisosteres of ester (+)-1, is described. The synthesized
      oxadiazoles were evaluated for their affinity to the DAT and their ability to
      inhibit monoamine reuptake at the DAT, NET, and 5HTT. The results show that
      affinity to the DAT and ability to inhibit the reuptake at the DAT, NET, and 5HTT
      is a function of the size of the substituent in the oxadiazole ring. (+)-(3R,4S)
      4beta-(4-Chlorophenyl)-1-methyl-3alpha-(3-methyl-1,2,4-oxadiazol-5-yl)piperidine
      [(+)-2a], which is structurally and pharmacologically most similar to the ester
      (+)-1 in this series, showed at least a 2-fold longer duration of action when
      compared to ester (+)-1.

PMID- 11514144
TI  - Amino acid derived sulfonamide hydroxamates as inhibitors of procollagen C
      proteinase: solid-phase synthesis of ornithine analogues.
AB  - A discussion of the solid-phase synthesis of ornithine derived sulfonamide
      hydroxamic acids is illustrated. These analogues are shown to be potent, non
      peptide inhibitors of procollagen C-proteinase (PCP).

PMID- 11514145
TI  - Improved synthesis and evaluation of 17-substituted aminoalkylgeldanamycin
      derivatives applicable to drug delivery systems.
AB  - The 17-methoxy group of geldanamycin was substituted with 1,3-diaminopropane and
      1,3-diamino-2-hydroxypropane to introduce a primary amino group useful for
      conjugation with targeting moieties and drug carriers. We have developed a
      procedure that has provided improved yield and reproducibility of the syntheses.
      Both geldanamycin derivatives demonstrated antiproliferative activity towards the
      human ovarian carcinoma cell line, A2780.

PMID- 11514146
TI  - Synthesis and potassium channel opening activity of substituted 10H
      benzo[4,5]furo[3,2-b]indole-and 5,10-dihydro-indeno[1,2-b]indole-1-carboxylic
      acids.
AB  - Compounds in a structurally novel series of substituted 10H-benzo[4,5]furo[3,2
      b]indole-1-carboxylic acids and related 5,10-dihydro-indeno[1,2-b]indole-1
      carboxylic acids were prepared and shown to possess potent, bladder-selective
      smooth muscle relaxant properties and thus are potentially useful for the
      treatment of urge urinary incontinence. Electrophysiological studies using rat
      detrusor myocytes have demonstrated that prototype compound 7 produces a
      significant increase in hyperpolarizing current, which is iberiotoxin (IbTx)
      reversed, thus consistent with activation of the large-conductance Ca(2+)
      activated potassium channel (BK(Ca)).

PMID- 11514147
TI  - Enzymatic synthesis of aza-l-tyrosines.
AB  - Tyrosine phenol-lyase from Citrobacter freundii synthesizes 2-aza-L-tyrosine and
      3-aza-L-tyrosine from 3-hydroxypyridine and 2-hydroxypyridine, respectively, and
      ammonium pyruvate.

PMID- 11514148
TI  - Biflavonoids as novel antituberculosis agents.
AB  - A series of naturally occurring and synthetic biflavonoids was evaluated for
      inhibitory activity against Mycobacterium tuberculosis H37Rv (Mtb). Compounds 6,
      24, and 25 demonstrated 96, 95, and 87% inhibition, respectively, at a screening
      concentration of 12.5 microg/mL. The type of linkage and the presence of methoxy-
      and nitro-substituents in biflavonoids may contribute to the observed inhibitory
      activity. The results of this study represent the discovery of biflavonoids as a
      potential new class of antituberculosis agent.

PMID- 11514149
TI  - Thrombin receptor (PAR-1) antagonists. Solid-phase synthesis of indole-based
      peptide mimetics by anchoring to a secondary amide.
AB  - A novel, 10-step, solid-phase method, based on a secondary amide linker, was
      developed to construct a diverse library of indole-based SFLLR peptide mimetics
      as thrombin receptor (protease-activated receptor 1, PAR-1) antagonists. The key
      steps include stepwise reductive alkylation, urea formation, and Mannich
      reaction. Screening of the library led to a quick development of the SAR and the
      significant improvement of PAR-1 activity.

PMID- 11514150
TI  - Stereoselective synthesis and antibacterial evaluation of 4-amido
      isothiazolidinone oxides.
AB  - Two well-defined oxidative chlorination-cyclization processes have been developed
      for the stereoselective synthesis of a variety of 4-amido-isothiazolidinone oxide
      derivatives. The stereochemistry of the cyclization products was confirmed by X
      ray crystallography. These new compounds were designed as bacterial serine
      protease inhibitors. In tests, some of them showed weak antibacterial activity.

PMID- 11514151
TI  - Novel lipase-catalysed enantioselective deacetylation of (+/-)-5-acetoxy-3-(4
      fluorophenyl)-2-phenylisoxazolidine.
AB  - (+/-)-5-Acetoxy-3-(4-fluorophenyl)-2-phenylisoxazolidine has been synthesised by
      a highly diastereoselective [3+2] cycloaddition reaction between alpha-(4
      fluorophenyl)-N-phenylnitrone and vinyl acetate in good yield. Candida rugosa
      lipase catalyses the deacetylation of this (+/-)-5-acetoxyisoxazolidine in a
      highly enantioselective fashion in diisopropyl ether containing n-butanol
      affording (-)-5-acetoxy-3-(4-fluorophenyl)-2-phenylisoxazolidine in 43% yield and
      >99% ee.

PMID- 11514152
TI  - Leishmanicidal activity of some stilbenoids and related heterocyclic compounds.
AB  - We have evaluated the leishmanicidal activity of some natural and semisynthetic
      dihydrostilbenoids and several compounds of other series of dihydrostilbamides,
      isoindoles, phthalazinones, imidazoisoindoles and pyrimidoisoindoles. The
      evaluation was performed in vitro, on cultures of cutaneous, mucocutaneous and
      visceral strains of Leishmania spp. The most potent and selective compounds of
      these series were the dihydrostilbene piperidides.

PMID- 11514153
TI  - Discovery of thioazepinone ligands for Src SH2: from non-specific to specific
      binding.
AB  - The structure-based design and synthesis of new thioazepinones as ligands for Src
      SH2 protein is presented. From benzothioazepinones, ligands with somewhat
      unspecific binding properties, simpler thioazepinones were designed, the best
      ones demonstrated nanomolar affinity for Src SH2. A few of these new ligands were
      crystallized with the protein and demonstrated a specific binding mode with the
      protein.

PMID- 11514154
TI  - 5-HT(3)R binding of lerisetron: an interdisciplinary approach to drug-Receptor
      interactions.
AB  - The design, synthesis, and use of lerisetron-based molecular probes to
      investigate the 5-HT(3)R binding site are described. A SAR study, which involved
      distance and electronic parameter modifications of lerisetron's N-benzyl group,
      resulted in the discovery of a partial agonist.

PMID- 11514155
TI  - Novel 3-(2-adamantyl)pyrrolidines with potent activity against influenza A virus
      identification of aminoadamantane derivatives bearing two pharmacophoric amine
      groups.
AB  - The 3-(2-adamantyl)pyrrolidines 8a-g, 14 were synthesized and evaluated for
      activity against influenza A virus. The parent N-H compound 14 was several times
      more active than amantadine against H(2)N(2) and H(3)N(2) influenza A virus. The
      combined use of NMR spectroscopy and computational chemistry showed that the
      conformation around the pyrrolidine-adamantyl carbon-carbon bond is trans and the
      pyrrolidine heterocycle has an envelope conformation with C-2 out of the plane of
      the other ring atoms. N-Dialkylaminoethyl substitution of compound 14 resulted in
      the potent diamine analogues 8e,f,g. Interestingly, their lactam amine precursors
      were also active. Compounds 8e,f,g are the first adamantane derivatives, bearing
      two amine groups, reported to be active against influenza A virus.

PMID- 11514156
TI  - Piperazine-based CCR5 antagonists as HIV-1 inhibitors. I: 2(S)-methyl piperazine
      as a key pharmacophore element.
AB  - Optimization of the piperidino-piperazines 1 and 2 provided early leads 3 and 4,
      which showed good activity in the CCR5-RANTES binding assay and in antiviral
      assays. A systematic study around these structures showed that the 2(S)-methyl
      piperazine is essential for CCR5 affinity, which is further enhanced by forming
      the 2,6-dimethyl benzamide of the piperidine.

PMID- 11514157
TI  - N-hydroxyformamide peptidomimetics as TACE/matrix metalloprotease inhibitors:
      oral activity via P1' isobutyl substitution.
AB  - N-Hydroxyformamide-class metalloprotease inhibitors were designed and
      synthesized, which have potent broad-spectrum activity versus matrix
      metalloproteases and TNF-alpha converting enzyme (TACE). Compound 13c possesses
      good oral and intravenous pharmacokinetics in the rat and dog.

PMID- 11514158
TI  - Synthesis of OSW-1 analogues and a dimer and their antitumor activities.
AB  - Five analogues, including a 16-epi-isomer (6), and a 3-terephthalic acid linked
      dimer (8) of OSW-1 were synthesized. Their inhibitory activities on P388 and A
      549 cells were detected.

PMID- 11514159
TI  - Artificial substrates of medium-chain elongating enzymes, hexaprenyl- and
      heptaprenyl diphosphate synthases.
AB  - We examined the reactivity of 3-alkyl group homologues of farnesyl diphosphate or
      isopentenyl diphosphate for medium-chain prenyl diphosphate synthases, hexaprenyl
      diphosphate- or heptaprenyl diphosphate synthase. But-3-enyl diphosphate, which
      lacks the methyl group at the 3-position of isopentenyl diphosphate, condensed
      only once with farnesyl diphosphate to give E-norgeranylgeranyl diphosphate by
      the action of either enzyme. However, norfarnesyl diphosphate was never accepted
      as an allylic substrate at all. 3-Ethylbut-3-enyl diphosphate also reacted with
      farnesyl diphosphate giving a mixture of (all-E)-3-ethyl-7,11,15
      trimethylhexadeca-2,6,10,14-tetraenyl- and (all-E)-3,7-diethyl-11,15,19
      trimethylicosa-2,6,10,14,18-pentaenyl diphosphates by hexaprenyl diphosphate
      synthase. On the other hand, heptaprenyl diphosphate synthase reaction of 3
      ethylbut-3-enyl diphosphate with farnesyl diphosphate gave only (all-E)-3-ethyl
      7,11,15-trimethylhexadeca-2,6,10,14-tetraenyl diphosphate.

PMID- 11514160
TI  - Coupling of the antennapedia third helix to a potent antagonist of the p53/hdm2
      protein-protein interaction.
AB  - The use of cell-membrane translocating sequences for intracellular delivery of
      peptides can be a powerful approach to validate drug discovery targets in
      cellular settings. To accomplish this, a protocol has been implemented to couple
      the antennapedia third helix (residues 43-58) to a potent antagonist of the
      p53/hdm2 protein-protein interaction without affecting its in vitro inhibitory
      activity.

PMID- 11514161
TI  - N,N-dibenzyl-N'-benzylidenehydrazines: potent competitive glucose-6-phosphatase
      catalytic enzyme inhibitors.
AB  - A novel class of N,N-dibenzyl-N'-benzylidenehydrazines as potent and competitive
      glucose-6-phosphatase catalytic site inhibitors are described. Optimisation of
      this series identified compounds with IC(50) values as low as 170 nM.

PMID- 11514162
TI  - Combinatorial synthesis of libraries of indole derivatives.
AB  - The synthesis of two indole derivative libraries is described. 2-Acyl-3-amino
      indoles 4 can easily be accessed by treatment of the intermediates 3 with bases
      in a one-pot reaction sequence whereas the reaction of the isolated intermediates
      5 (R(3)=aromatic-, heteroaromatic, or cycloalkyl) with acid chlorides yielded the
      novel indole derivatives 6. The products were purified by reversed phase column
      chromatography and obtained in multi-milligram quantities in acceptable yields.

PMID- 11514163
TI  - Discovery of (R)-1-[2-hydroxy-3-(4-hydroxy-phenyl)-propyl]-4-(4-methyl-benzyl)
      piperidin-4-ol: a novel NR1/2B subtype selective NMDA receptor antagonist.
AB  - Starting from Ro-25-6981 as a lead compound, highly potent and selective NR1/2B
      subtype selective NMDA receptor antagonists, with low activity at alpha(1)
      adrenergic receptors were developed.

PMID- 11514164
TI  - Conformationally restricted indolopiperidine derivatives as potent CCR2B receptor
      antagonists.
AB  - The preparation and biological evaluation of a series of indolopiperidine CCR2B
      receptor antagonists possessing a conformationally restricted C-5 linker chain in
      combination with a restricted piperidine ring are described. Compared to the
      parent compound 1, analogue 8 shows a dramatic improvement in selectivity against
      a range of 5-HT and dopaminergic receptors.

PMID- 11514165
TI  - Caged Q-rhodamine dextran: a new photoactivated fluorescent tracer.
AB  - An amine-reactive caged rhodamine was synthesized and conjugated to aminodextran.
      The resulting tracer was injected into a single cell zebrafish embryo, and a
      portion of the tracer was photolyzed in a single cell after development. The
      resulting fluorescent cell was imaged by fluorescence microscopy through a single
      round of cell division.

PMID- 11514166
TI  - Design and synthesis of novel antibacterial agents with inhibitory activity
      against DNA polymerase III.
AB  - 4-Substituted 2-amino-6-(anilino)pyrimidines have been found to be selective
      inhibitors of DNA polymerase III, a replicative enzyme known to be essential in
      the DNA synthesis of Gram-positive bacteria. Among the analogues, 18 displayed an
      IC(50) of 10 microM against DNA polymerase III from Staphylococcus aureus.

PMID- 11514167
TI  - The discovery of anthranilic acid-based MMP inhibitors. Part 2: SAR of the 5
      position and P1(1) groups.
AB  - A novel series of anthranilic acid-based inhibitors of MMP-1, MMP-9, MMP-13, and
      TACE was prepared and evaluated. Selective inhibitors of MMP-9, MMP-13, and TACE
      were identified, including the potent, orally active MMP-13 inhibitor 4p.

PMID- 11514168
TI  - Anticancer properties for 4,4'-dihydroxybenzophenone-2,4-dinitrophenylhydrazone
      (A-007)/3,7-diaminophenothiazin-5-ium double salts.
AB  - 4,4'-Dihydroxybenzophenone-2,4-dinitrophenylhydrazone (A-007) formed stable
      double salts with phenothiazin-5-ium salts (2a-d), which have improved in vitro
      anticancer activities, as compared to A-007 alone. The stable salt between
      methylene blue (2a) and A-007 allowed the latter to diffuse into the dermis
      layers of skin. It is anticipated that these new salts will allow A-007 to
      penetrate into the deep lymphatic/vascular channels of the dermis, which contain
      metastatic cancer cells, and improve in vivo anticancer activities.

PMID- 11514169
TI  - Synthesis and antiproliferative activity of epoxy and bromo compounds derived
      from estrone.
AB  - Based on biological properties of epoxyquinols from natural sources, bromo and
      epoxyquinols derived from estrone were synthesized and screened against Fem-X,
      HeLa and K(562) cell lines. Evidence was found that the bromine atom and the
      epoxy moiety significantly increase the antiproliferative activity within the
      series.

PMID- 11514170
TI  - Synthesis and pharmacology of modified amidine isoxazoline glycoprotein IIb/IIIa
      receptor antagonists.
AB  - Selective antagonism of the platelet GPIIb/IIIa receptor represents an attractive
      mechanism for the prevention and treatment of a number of thrombotic disease
      states. The antiplatelet activity of the oral GPIIb/IIIa receptor antagonists DMP
      754 and DMP 802 have been disclosed. In this paper, the synthesis and biological
      evaluation of a series of potent N-substituted benzamidine isoxazolines are
      explored. The effect of benzamidine substitution on the duration of antiplatelet
      efficacy in dog is presented.

PMID- 11514171
TI  - Design, synthesis and antiproliferative activity of tripentones: a new series of
      antitubulin agents.
AB  - Structure-activity relationship studies of a new series of tripentones
      (thieno[2,3-b]pyrrolizin-8-ones), led us to prepare several derivatives with
      antiproliferative activities. The most promising 3-(3-hydroxy-4
      methoxyphenyl)thieno[2,3-b]pyrrolizin-8-one 20 (leukemia L1210, IC(50)=15 nM) was
      shown to be a potent inhibitor of tubulin polymerization.

PMID- 11514172
TI  - Identification of selective inhibitors of cyclin dependent kinase 4.
AB  - A new structural type of kinase inhibitor, containing a benzocarbazole nucleus,
      has been identified. Members of the series are selective for inhibition of the
      cyclin dependent kinase family of enzymes. Although the cdks are highly
      homologous, representatives of the series showed intra-cdk selectivities,
      especially for cdk4. SAR studies elucidated the important features of the
      molecules for inhibition.

PMID- 11514173
TI  - Novel 4-piperidinopyridine inhibitors of oxidosqualene cyclase-lanosterol
      synthase derived by consideration of inhibitor pK(a).
AB  - Potent inhibition of rat microsomal oxidosqualene cyclase-lanosterol synthase
      (OSC) was maintained after structural modification of the 4-piperidinopyridine
      OSC inhibitor series. These novel analogues with a much lower pK(a) range (5.8
      6.7) gave potent oral inhibition of rat cholesterol biosynthesis (8 ED(80) 0.7
      mg/kg), and diminished effects on rat feeding after a 100 mg/kg oral dose.

PMID- 11514174
TI  - Absolute stereostructures of novel norcadinane- and trinoreudesmane-type
      sesquiterpenes with nitric oxide production inhibitory activity from Alpinia
      oxyphylla.
AB  - Novel 14-norcadinane-type sesquiterpenes, oxyphyllenodiols A and B, and 11,12,13
      trinoreudesmane-type sesquiterpenes, oxyphyllenones A and B, were isolated from
      the methanolic extract of kernels of Alpinia oxyphylla. The absolute
      stereostructures of these norsesquiterpenes were determined on the basis of
      physicochemical and chemical evidence. In addition, oxyphyllenodiol A and
      oxyphyllenone A were found to inhibit the NO production in lipopolysaccharide
      activated macrophages.

PMID- 11514175
TI  - Synthesis of 6-(2-thienyl)purine nucleoside derivatives that form unnatural base
      pairs with pyridin-2-one nucleosides.
AB  - Unnatural bases, 2-amino-6-(2-thienyl)purine and 2-amino-6-(2-furanyl)purine,
      were newly designed to replace the previously developed purine analogue, 2-amino
      6-(N,N-dimethylamino)purine, which specifically pairs with pyridin-2-one. These
      nucleoside derivatives were synthesized via the 6-substitution of 6-iodopurine
      nucleosides with tributylstannylthiophene or tributylstannylfuran. As compared
      with 2-amino-6-(N,N-dimethylamino)purine, 2-amino-6-(2-thienyl)purine reduced the
      interference in the stacking interactions with the neighboring bases in a DNA
      duplex and improved the efficiency of the enzymatic incorporation of the
      nucleoside triphosphate of pyridin-2-one opposite the unnatural base.

PMID- 11514177
TI  - Alternative splicing of potassium channels: a dynamic switch of cellular
      excitability.
AB  - Alternative splicing of pre-messenger RNA and reversible protein phosphorylation
      are fundamental mechanisms for regulating protein structure and function. Recent
      studies of one class of potassium channel (BK(Ca)) reveal dynamic reciprocal
      interactions between pre-mRNA splicing and protein phosphorylation. Splicing is
      regulated by phosphorylation, and exon selection determines the sensitivity of
      the channel protein to regulation by protein phosphorylation. These studies
      reveal a powerful dynamic molecular switch to determine cellular excitability.

PMID- 11514190
TI  - Ran GTPase: a master regulator of nuclear structure and function during the
      eukaryotic cell division cycle?
AB  - Ran is an abundant GTPase that is highly conserved in eukaryotic cells and has
      been implicated in many aspects of nuclear structure and function, especially
      determining the directionality of nucleocytoplasmic transport during interphase.
      However, cell-free systems have recently shown that Ran plays distinct roles in
      mitotic spindle assembly and nuclear envelope (NE) formation in vitro. During
      spindle assembly, Ran controls the formation of complexes with importins, the
      same effectors that control nucleocytoplasmic transport. Here, we review these
      advances and discuss a general model for Ran in the coordination of nuclear
      processes throughout the cell division cycle via common biochemical mechanisms.

PMID- 11514191
TI  - Signal transduction by tumor necrosis factor and its relatives.
AB  - Tumor necrosis factor alpha (TNFalpha) is a potent proinflammatory cytokine that
      plays an important role in immunity and inflammation, and in the control of cell
      proliferation, differentiation and apoptosis. TNFalpha is also the founding
      member of a still growing family of cytokines with diverse bioregulatory
      functions. Considerable progress has been made in understanding the molecular
      mechanisms that mediate TNFalpha-induced cellular responses. Binding of TNFalpha
      to its two receptors, TNFR1 and TNFR2, results in recruitment of signal
      transducers that activate at least three distinct effectors. Through complex
      signaling cascades and networks, these effectors lead to the activation of
      caspases and two transcription factors, AP-1 and NF-kappaB. Similar signaling
      mechanisms are likely to be used by other members of the TNF family. This review
      focuses on proteins that transduce the signals generated at TNF receptors to
      nuclear targets such as AP-1 and NF-kappaB.

PMID- 11514192
TI  - The adenomatous polyposis coli protein: in the limelight out at the edge.
AB  - Truncation mutations in the adenomatous polyposis coli protein (APC) are
      responsible for familial and sporadic colonic tumours. APC is best known for its
      role in regulating beta-catenin, an important mediator of cell adhesion and a
      transcriptional activator. However, recent studies indicate that APC has
      additional roles in cytoskeletal regulation. It binds to microtubules directly
      and indirectly. Furthermore, indirect connections between APC and the actin
      cytoskeleton have also been described. Here, we integrate recent information
      describing the association between APC and the cytoskeleton to illustrate how
      this multifaceted protein might link different cytoskeletal elements to each
      other and to cellular signaling pathways.

PMID- 11514193
TI  - Clathrin-mediated endocytosis: membrane factors pull the trigger.
AB  - Clathrin-mediated endocytosis is a vesicular transport event involved in the
      internalization and recycling of receptors participating in signal transduction
      events and nutrient import as well as in the reformation of synaptic vesicles.
      Recent studies in vitro and in living cells have provided a number of new
      insights into the initial steps of clathrin-coated vesicle formation and the
      membrane factors involved in this process. The unexpected complexity of these
      interactions at the cytosol-membrane interface suggests that clathrin-coated
      vesicle assembly is a highly cooperative process occurring under tight regulatory
      control. In this review, we focus on the role of membrane proteins and lipids in
      the nucleation of clathrin-coated pits and provide a hypothetical model for the
      early steps in clathrin-mediated endocytosis.

PMID- 11514194
TI  - Profile--Erin O'Shea. Interviewed by Rabiya S. Hunter.

PMID- 11514195
TI  - Ingenious gene generation.

PMID- 11514197
TI  - Size matters?

PMID- 11514216
TI  - HIV/AIDS analysts concerned by trends.

PMID- 11514218
TI  - Targeting exported substrates to the Yersinia TTSS: different functions for
      different signals?
AB  - Many Gram-negative pathogens utilize a type III secretion system (TTSS) to inject
      toxins into the cytosol of eukaryotic cells. Previous studies have indicated that
      exported substrates are targeted to the Yersinia TTSS via the coding regions of
      their 5' mRNA sequences, as well as by their cognate chaperones. However, recent
      results from our laboratory have challenged the role of mRNA targeting signals,
      as we have shown that the amino termini of exported substrates are crucial for
      type III secretion. Here, we discuss the nature of these amino-terminal secretion
      signals and propose a model for the secretion of exported substrates by amino
      terminal and chaperone-mediated signals. In addition, we discuss the roles of
      chaperones as regulators of virulence gene expression and present models
      suggesting that such regulation can occur independently of the delivery of their
      substrates to the secretion apparatus.

PMID- 11514219
TI  - Can a 'flawless' live vector vaccine strain be engineered?
AB  - The efficiency of any live bacterial vector vaccine hinges on its ability to
      present sufficient foreign antigen to the human immune system to initiate the
      desired protective immune response(s). However, synthesis of sufficient levels of
      heterologous antigen can result in an increase in metabolic burden with an
      accompanying decrease in the fitness of the live vector, which can ultimately
      lower desired immune responses to both live vector and heterologous antigen.
      Here, we explore the underlying mechanisms of metabolic load and propose ways of
      minimizing such burdens to enhance the fitness and immunogenicity of Salmonella
      based live vector vaccines.

PMID- 11514220
TI  - Viruses and autoimmune disease--two sides of the same coin?
AB  - Some viruses have the ability to modulate the development of autoimmune diseases.
      Virus infections have long been associated with the exacerbation of autoimmune
      disease, however, there is also evidence that viruses can actually protect
      against autoimmune disease. Several experimental models have been developed to
      investigate how some virus infections can prime for and trigger autoimmunity
      whereas others ameliorate the pathway leading to clinical disease. It is possible
      that the type I interferons, via interleukin 12, provide the link between viruses
      and autoimmunity.

PMID- 11514221
TI  - The pathobiology of Aspergillus fumigatus.
AB  - Aspergillus fumigatus is the most prevalent airborne fungal pathogen in developed
      countries, and in immunocompromised patients causes a usually fatal invasive
      aspergillosis (IA). Understanding the pathobiology of this fungal species
      requires not only analysis of the putative fungal virulence factors that
      stimulate fungal growth and/or survival in the lung environment, but also
      knowledge of the immune factors containing A. fumigatus in the immunocompetent
      host that can be debilitated by immunosuppressive therapies, triggering IA.
      Although the incidence of IA has dramatically increased in recent years, progress
      in these areas has been limited and, as yet, a single, true virulence factor has
      not been identified and the mechanisms responsible for protective immunity
      against A. fumigatus have yet to be elucidated.

PMID- 11514222
TI  - Campylobacter jejuni--microtubule-dependent invasion.
AB  - Campylobacter jejuni is the leading bacterial cause of food-borne illness
      worldwide and a major cause of Guillain-Barre paralysis. Recent molecular and
      cellular studies of one well-characterized C. jejuni strain have begun to unravel
      the details of an unusual microtubule-dependent (actin-filament-independent) gut
      invasion mechanism, through which at least some C. jejuni initiate disease.
      Although responsible for causing a human dysenteric syndrome remarkably similar
      to that triggered by Shigella spp., current evidence suggests that C. jejuni use
      some markedly different molecular mechanisms of pathogenesis compared with
      shigellae.

PMID- 11514223
TI  - Divalent-metal transport by NRAMP proteins at the interface of host-pathogen
      interactions.
AB  - The NRAMP family of divalent-metal transporters plays a key role in the
      homeostasis of iron and other metals. NRAMP2 (DMT1) acts as an iron-uptake
      protein in both the duodenum and in peripheral tissues. NRAMP1 functions as a
      divalent-metal efflux pump at the phagosomal membrane of macrophages and
      neutrophils, and mutations in NRAMP1 cause susceptibility to several
      intracellular pathogens. NRAMP homologues have been identified in bacteria and
      are involved in acquiring divalent metals from the extracellular environment.
      Interestingly, bacterial and mammalian NRAMP proteins would compete for the same
      essential substrates within the microenvironment of the phagosome, at the
      interface of host-pathogen interactions.

PMID- 11514224
TI  - Proteasome inhibitors: from research tools to drug candidates.
AB  - The 26S proteasome is a 2.4 MDa multifunctional ATP-dependent proteolytic
      complex, which degrades the majority of cellular polypeptides by an unusual
      enzyme mechanism. Several groups of proteasome inhibitors have been developed and
      are now widely used as research tools to study the role of the ubiquitin
      proteasome pathway in various cellular processes, and two inhibitors are now in
      clinical trials for treatment of multiple cancers and stroke.

PMID- 11514225
TI  - The anti-inflammatory natural product parthenolide from the medicinal herb
      Feverfew directly binds to and inhibits IkappaB kinase.
AB  - BACKGROUND: Biologically active natural products continue to be useful in the
      exploration and control of intracellular signaling processes. For example, the
      sesquiterpene lactone parthenolide from the anti-inflammatory medicinal herb
      Feverfew (Tanacetum parthenium) appears to inhibit the pro-inflammatory signaling
      pathway. Parthenolide's direct molecular target, however, remains unknown. We set
      out to identify the molecular mechanisms of parthenolide's anti-inflammatory
      activity. RESULTS: A parthenolide affinity reagent was synthesized and shown to
      bind directly to and inhibit IkappaB kinase beta (IKKbeta), the kinase subunit
      known to play a critical role in cytokine-mediated signaling. Mutation of
      cysteine 179 in the activation loop of IKKbeta abolished sensitivity towards
      parthenolide. Moreover, we showed that parthenolide's in vitro and in vivo anti
      inflammatory activity is mediated through the alpha-methylene gamma-lactone
      moiety shared by other sesquiterpene lactones. CONCLUSIONS: In recent years, the
      multi-subunit IKK complex has been shown to be responsible for cytokine-mediated
      stimulation of genes involved in inflammation and as such represents an
      attractive target for pharmaceutical intervention. Our finding that parthenolide
      targets this kinase complex provides a possible molecular basis for the anti
      inflammatory properties of parthenolide. In addition, these results may be useful
      in the development of additional anti-inflammatory agents.

PMID- 11514227
TI  - Alterations of lipoxygenase specificity by targeted substrate modification and
      site-directed mutagenesis.
AB  - BACKGROUND: Mammalian lipoxygenases (LOXs) are categorised with respect to their
      positional specificity of arachidonic acid oxygenation. However, the mechanistic
      basis for this classification is not well understood. To gain a deeper insight
      into the structural basis of LOX specificity we determined the reaction
      characteristics of wild-type and mutant mammalian LOX isoforms with native and
      synthetic fatty acids substrates. RESULTS: The rabbit 15-LOX is capable of
      catalysing major 12-lipoxygenation when the volume of the substrate-binding
      pocket is enlarged. These alterations in the positional specificity can be
      reversed when bulky residues are introduced at the omega end of the substrate.
      Simultaneous derivatisation of both ends of fatty acids forces a 15-LOX-catalysed
      5-lipoxygenation and this reaction involves an inverse head-to-tail substrate
      orientation. In contrast, for arachidonic acid 5-lipoxygenation by the human 5
      LOX the substrate fatty acid may not be inversely aligned. The positional
      specificity of this isoenzyme may be related to its voluminous substrate-binding
      pocket. Site-directed mutagenesis, which leads to a reduction of active site
      volume, converts the 5-LOX to a 15-lipoxygenating enzyme species. CONCLUSIONS:
      The positional specificity of LOXs is not an invariant enzyme property but
      depends on the substrate structure and the volume of the substrate-binding
      pocket. 15-LOX-catalysed 5-lipoxygenation involves an inverse substrate alignment
      but this may not be the case for 5-LOXs. Thus, both theories for the mechanistic
      basis of 5-lipoxygenation (straight and inverse substrate orientation) appear to
      be correct for different LOX isoforms.

PMID- 11514226
TI  - Ingenol esters induce apoptosis in Jurkat cells through an AP-1 and NF-kappaB
      independent pathway.
AB  - BACKGROUND: Ingenol derivatives have received constant and multidisciplinary
      attention on account of their pleiotropic pattern of biological activity. This
      includes activation of protein kinase C (PKC), tumour-promotion, anticancer, and
      anti-HIV properties, and the possibility of dissecting co-cancerogenic and
      clinically useful activities has been demonstrated. Certain ingenol esters show
      powerful anticancer activity, and a structure-activity relationship model to
      discriminate between their apoptotic and non-apoptotic properties has been
      developed. RESULTS: The polyhydroxylated southern region of ingenol was
      selectively modified, using the anticancer and PKC activator ingenol 3,20
      dibenzoate (IDB) as a lead compound. The evaluation of IDB analogues in apoptosis
      assays showed strict structure-activity relationships, benzoylation of the 20
      hydroxyl being required to trigger apoptosis through a pathway involving caspase
      3 and occurring at the specific cell cycle checkpoint that controls the S-M phase
      transition. Conversely, a study on the activation of the PKC-dependent
      transcription factors AP-1 and NF-kappaB by IDB analogues showed significant
      molecular flexibility, including tolerance to changes at the 3- and 20-hydroxyls.
      IDB-induced apoptosis was independent of activation of PKC, since it was not
      affected by treatment with the non-isoform-selective PKC inhibitor GF 109230X0.
      CONCLUSIONS: Remarkable deviations from the tumour-promotion pharmacophore were
      observed for both the apoptotic and the PKC-activating properties of IDB
      analogues, showing that ingenol is a viable template to selectively target
      crucial pathways involved in tumour promotion and development. Since the
      apoptotic and the PKC-activating properties of ingenoids are mediated by
      different pathways and governed by distinct structure-activity relationships, it
      is possible to dissect them by suitable chemical modification. In this context,
      the esterification pattern of the 5- and 20-hydroxyls is critical.

PMID- 11514228
TI  - Active site labeling of the gentamicin resistance enzyme AAC(6')-APH(2") by the
      lipid kinase inhibitor wortmannin.
AB  - BACKGROUND: Aminoglycoside antibiotic resistance is largely the result of the
      production of enzymes that covalently modify the drugs including kinases (APHs)
      with structural and functional similarity to protein and lipid kinases. One of
      the most important aminoglycoside resistance enzymes is AAC(6')-APH(2"), a
      bifunctional enzyme with both aminoglycoside acetyltransferase and kinase
      activities. Knowledge of enzyme active site structure is important in deciphering
      the molecular mechanism of antibiotic resistance and here we explored active site
      labeling techniques to study AAC(6')-APH(2") structure and function. RESULTS:
      AAC(6')-APH(2") was irreversibly inactivated by wortmannin, a potent
      phosphatidylinositol 3-kinase inhibitor, through the covalent modification of a
      conserved lysine in the ATP binding pocket. 5'-[p
      (Fluorosulfonyl)benzoyl]adenosine, an electrophilic ATP analogue and known
      inactivator of other APH enzymes such as APH(3')-IIIa, did not inactivate AAC(6')
      APH(2"), and reciprocally, wortmannin did not inactivate APH(3')-IIIa.
      CONCLUSIONS: These distinct active site label sensitivities point to important
      differences in aminoglycoside kinase active site structures and suggest that
      design of broad range, ATP binding site-directed inhibitors against APHs will be
      difficult. Nonetheless, given the sensitivity of APH enzymes to both protein and
      lipid kinase inhibitors, potent lead inhibitors of this important resistance
      enzyme are likely to be found among the libraries of compounds directed against
      other pharmacologically important kinases.

PMID- 11514229
TI  - Structural requirements for the biosynthesis of backbone cyclic peptide
      libraries.
AB  - BACKGROUND: Combinatorial methods for the production of molecular libraries are
      an important source of ligand diversity for chemical biology. Synthetic methods
      focus on the production of small molecules that must traverse the cell membrane
      to elicit a response. Genetic methods enable intracellular ligand production, but
      products must typically be large molecules in order to withstand cellular
      catabolism. Here we describe an intein-based approach to biosynthesis of backbone
      cyclic peptide libraries that combines the strengths of synthetic and genetic
      methods. RESULTS: Through site-directed mutagenesis we show that the DnaE intein
      from Synechocystis sp. PCC6803 is very promiscuous with respect to peptide
      substrate composition, and can generate cyclic products ranging from four to nine
      amino acids. Libraries with five variable amino acids and either one or four
      fixed residues were prepared, yielding between 10(7) and 10(8) transformants. The
      majority of randomly selected clones from each library gave cyclic products.
      CONCLUSIONS: We have developed a versatile method for producing intracellular
      libraries of small, stable cyclic peptides. Genetic encoding enables facile
      manipulation of vast numbers of compounds, while low molecular weight ensures
      ready pharmacophore identification. The demonstrated flexibility of the method
      towards both peptide length and composition makes it a valuable addition to
      existing methods for generating ligand diversity.

PMID- 11514230
TI  - Analysis of the prodiginine biosynthesis gene cluster of Streptomyces coelicolor
      A3(2): new mechanisms for chain initiation and termination in modular
      multienzymes.
AB  - BACKGROUND: Prodiginines are a large family of pigmented oligopyrrole antibiotics
      with medicinal potential as immunosuppressants and antitumour agents that are
      produced by several actinomycetes and other eubacteria. Recently, a gene cluster
      in Streptomyces coelicolor encoding the biosynthesis of undecylprodiginine and
      butyl-meta-cycloheptylprodiginine has been sequenced. RESULTS: Using sequence
      comparisons, functions have been assigned to the majority of the genes in the
      cluster, several of which encode homologues of enzymes involved in polyketide,
      non-ribosomal peptide, and fatty acid biosynthesis. Based on these assignments, a
      complete pathway for undecylprodiginine and butyl-meta-cycloheptylprodiginine
      biosynthesis in S. coelicolor has been deduced. Gene knockout experiments have
      confirmed the deduced roles of some of the genes in the cluster. CONCLUSIONS: The
      analysis presented provides a framework for a general understanding of the
      genetics and biochemistry of prodiginine biosynthesis, which should stimulate
      rational approaches to the engineered biosynthesis of novel prodiginines with
      improved immunosuppressant or antitumour activities. In addition, new mechanisms
      for chain initiation and termination catalysed by hitherto unobserved domains in
      modular multienzyme systems have been deduced.

PMID- 11514231
TI  - Quantitative analysis of the stabilization by substrate of Staphylococcus aureus
      PC1 beta-lactamase.
AB  - BACKGROUND: The stabilization of enzymes in the presence of substrates has been
      recognized for a long time. Quantitative information regarding this phenomenon
      is, however, rather scarce since the enzyme destroys the potential stabilizing
      agent during the course of the experiments. In this work, enzyme unfolding was
      followed by monitoring the progressive decrease of the rate of substrate
      utilization by the Staphylococcus aureus PC1 beta-lactamase, at temperatures
      above the melting point of the enzyme. RESULTS: Enzyme inactivation was directly
      followed by spectrophotometric measurements. In the presence of substrate
      concentrations above the K(m) values, significant stabilization was observed with
      all tested compounds. A combination of unfolding kinetic measurements and
      enzymatic studies, both under steady-state and non-steady-state regimes, allowed
      most of the parameters characteristic of the two concurrent phenomena (i.e.
      substrate hydrolysis and enzyme denaturation) to be evaluated. In addition,
      molecular modelling studies show a good correlation between the extent of
      stabilization, and the magnitude of the energies of interaction with the enzyme.
      CONCLUSIONS: Our analysis indicates that the enzyme is substantially stabilized
      towards heat-induced denaturation, independently of the relative proportions of
      non-covalent Henri-Michaelis complex (ES) and acyl-enzyme adduct (ES*). Thus, for
      those substrates with which the two catalytic intermediates are expected to be
      significantly populated, both species (ES and ES*) appear to be similarly
      stabilized. This analysis contributes a new quantitative approach to the problem.

PMID- 11514232
TI  - Bile salt-dependent lipase: its pathophysiological implications.

PMID- 11514233
TI  - Snake inhibitors of phospholipase A(2) enzymes.
AB  - Phospholipase A(2) (PLA(2)) enzymes consist of a large family of proteins which
      share the same enzymatic function and display considerable sequence homology.
      These enzymes have been identified and characterised in mammalian tissue and
      snake venoms. Numerous physiological functions have been attributed to mammalian
      PLA(2)s and they are nontoxic. In comparison, venom PLA(2)s are toxic and induce
      a variety of pharmacological effects that are probably mediated via membrane
      receptors. Snake PLA(2) inhibitors (PLIalpha), with a similar structure to the M
      type receptor, have been identified as soluble complexes in the serum of
      viperinae and crotalinae snakes. These inhibitors showed selective binding to
      crotalid group II PLA(2)s and appeared to be restricted to the serum of this
      snake family. Analysis of PLA(2) binding to recombinant fragments of PLIalpha
      indicated that the CRD region was most likely responsible for enzyme inhibition.
      A second type of inhibitor, PLIbeta, has been identified in serum from one
      viperid snake and consists of a leucine-rich structure. The third type of
      inhibitor, PLIgamma, was found in the serum of five snake families and contains a
      pattern of cysteine residues that define a three-finger structure. PLIgamma
      inhibitors isolated from the serum of Elapidae, Hydrophidae, Boidae and
      Colubridae families were able to inhibit a broad range of enzymes including the
      nontoxic mammalian group IB and IIA PLA(2)s, and bee venom group III PLA(2).
      However, differences in the binding affinities indicated specificity for
      particular PLA(2)s. A different representation has emerged for crotalid and
      viperid snakes. Their PLIgammas did not inhibit bee venom group III, mammalian
      group IB and IIA enzymes. Furthermore, inhibition data for the gamma-type
      inhibitor from Crotalus durissus terrificus (CICS) showed that this inhibitor was
      specific for viperid beta-neurotoxins and did not inhibit beta-neurotoxins from
      elapids [1]. Further studies are required to determine if this phenomenon is true
      for all gamma-type inhibitors from Crotalidae snakes. The relative distribution
      of these inhibitors, their specificities and the structural features involved in
      binding are discussed in this review.

PMID- 11514234
TI  - Conjugated linoleic acid isomers have differential effects on triglyceride
      secretion in Hep G2 cells.
AB  - The effect of different conjugated linoleic acid (CLA) isomers (trans-10,cis-12
      (t10,c12)-CLA and cis-9,trans-11 (c9,t11)-CLA), compared with oleic acid (OA) and
      linoleic acid (LA), on hepatic lipid synthesis and secretion were investigated in
      Hep G2 cells. The cells were incubated in a medium containing 1 mmol/l fatty acid
      bovine serum albumin (BSA) complex for 5 h, with BSA alone as control.
      [(3)H]Glycerol and [(14)C]acetate were used to monitor lipid synthesis and
      secretion. The results show that cellular uptake rates of these fatty acids were
      similar. Incubation with OA, t10,c12-CLA, c9,t11-CLA and LA resulted in 6-, 4-, 2
      and 1.8-fold increases in intracellular [(3)H]triglyceride ([(3)H]TG) compared
      with incubation with BSA alone. OA, LA and c9,t11-CLA increased [(3)H]TG
      secretion 3.6-, 2.5- and 1.2-fold above the control, whereas t10,c12-CLA markedly
      suppressed the secretion of [(3)H]TG. Hepatic secretion of TG mass increased 3.5
      , 3.3-, 2.7- and 1.5-fold in the cells incubated with OA, LA, c9,t11-CLA and
      t10,c12-CLA, respectively. Since the secreted TG is mainly contained in very low
      density lipoproteins (VLDL), the decreased ([(3)H])TG secretion by t10,c12-CLA
      reflects a diminished secretion of VLDL. With respect to cholesterol synthesis OA
      was more effective in stimulating the incorporation of [(14)C]acetate into
      cellular total cholesterol followed in descending order by LA, c9,t11-CLA and
      t10,c12-CLA. In conclusion, the biological properties of 18-carbon fatty acids
      are clearly influenced by both the number and (geometric) positions of their
      double bonds. Furthermore t10,c12-CLA is more effective than c9,t11-CLA on
      suppressing hepatic TG secretion in vitro.

PMID- 11514235
TI  - Evidence for the association of ultraviolet-C and H(2)O(2)-induced apoptosis with
      acid sphingomyelinase activation.
AB  - Ceramide appears to be a potent second messenger implicated in the regulation of
      diverse cellular processes such as cell growth and differentiation, gene
      transcription, ligand binding, and cell death. Environmental stress-induced
      apoptosis is believed to be associated with the sphingomyelin degradation
      pathway, which generates ceramide as a second messenger in initiating the
      apoptosis response. To date, two distinct sphingomyelinases, a lysosomal acid
      sphingomyelinase (ASM), which is deficient in patients affected with types A and
      B Niemann-Pick disease (NPD), and a neutral, magnesium-dependent sphingomyelinase
      (NSM), are candidate enzymes which respond to apoptotic stimulations and cause
      sphingomyelin hydrolysis and subsequent ceramide generation. Using Epstein-Barr
      virus (EBV)-transformed lymphoblast cells from type A NPD patient which have
      defined splicing site mutation in the ASM gene, we showed that ASM-deficient
      cells were defective in ultraviolet-C (UV-C) and hydrogen peroxide (H(2)O(2))
      induced apoptosis. As another induction of apoptosis, we exposed this cell line
      to serum starvation which influences to p53 expression and leads to apoptosis.
      There were no differences by the degree of apoptosis between ASM-deficient
      lymphoblast cells and normal lymphoblast cells. These results are evidence that
      ASM plays one of the important roles in apoptosis induction by UV-C and H(2)O(2).

PMID- 11514236
TI  - Energy-dependent export of the 13-oxooctadecadienoic acid-glutathione conjugate
      from HT-29 cells and plasma membrane vesicles.
AB  - Numerous studies have identified members of the multidrug resistance protein
      (MRP) family of ABC transporters as ATP-dependent GS-X pumps responsible for
      export of various xenobiotic conjugates, and the few known glutathione conjugates
      of endogenous metabolites. In the present study we have investigated the
      possibility that the glutathione conjugate of 13-oxooctadecadienoic acid (13-OXO
      SG), is exported from HT-29 cells by one of these GS-X pumps. The precursor 13
      oxooctadecadienoic acid (13-OXO) is a metabolic oxidation product of linoleic
      acid. The transport of 13-OXO-SG is compared to that of the glutathione conjugate
      of chlorodinitrobenzene (DNP-SG). The results show that the efflux of 13-OXO-SG
      is ATP-dependent. In cultured HT-29 cells as well as in inside-out vesicles
      prepared from these cells, significant inhibition of conjugate export is achieved
      by the energy disrupters, beta,gamma-methylene ATP, sodium vanadate, and 2
      deoxyglucose. Significant inhibition of the vesicle-mediated transport is also
      observed in the presence of genistein and verapamil. In inside-out vesicles, the
      transport of both conjugates exhibits saturation with an apparent K(m) of 325.5
      microM and a V(max) of 0.0669 nmol/mg protein per min for 13-OXO-SG and a K(m) of
      169 microM and a V(max) of 0.496 nmol/mg protein per min for DNP-SG. Furthermore,
      co-inhibition is observed when both conjugates are present simultaneously which
      is consistent with the involvement of common pumps. The data in this report
      demonstrate the involvement of an ATP-dependent pump in the metabolic disposition
      of endogenously derived metabolites of linoleic acid.

PMID- 11514237
TI  - Characterisation of human peroxisomal 2,4-dienoyl-CoA reductase.
AB  - Based on the primary structure of the rat peroxisomal 2,4-dienoyl-CoA reductase
      (M. Fransen, P.P. Van Veldhoven, S. Subramani, Biochem. J. 340 (1999) 561-568),
      the cDNA of the human counterpart was cloned. It contained an open reading frame
      of 878 bases encoding a protein of 291 amino acids (calculated molecular mass
      30778 Da), being 83% identical to the rat reductase. The gene, encompassing nine
      exons, is located at chromosome 16p13. Bacterially expressed poly(His)-tagged
      reductase was active not only towards short and medium chain 2,4-dienoyl-CoAs,
      but also towards 2,4,7,10,13,16,19-docosaheptaenoyl-CoA. Hence, the reductase
      does not seem to constitute a rate limiting step in the peroxisomal degradation
      of docosahexaenoic acid. The reduction of docosaheptaenoyl-CoA, however, was
      severely decreased in the presence of albumin.

PMID- 11514238
TI  - The age-related differences in obese and fatty acid synthase gene expression in
      white adipose tissue of rat.
AB  - To determine if the age-dependent increase of adiposity is directly related to
      altered obese (ob) and fatty acid synthase (FAS) gene expression, we assessed an
      adiposity index, leptin and FAS mRNA levels, FAS activity in perirenal adipose
      tissue and serum leptin concentration in rats aged 1, 2, 3, 6 and 20 months. The
      results indicate that there are two distinct phases of changes in perirenal white
      adipose tissue leptin mRNA level and serum leptin concentration. The first phase,
      between 1 and 3 months of the animals' lives, was characterized by a strong
      positive correlation between adiposity index and leptin mRNA level as well as
      serum leptin concentration. In the second phase (over 3 months) no significant
      changes of leptin mRNA and serum concentration occurred. A close correlation
      between the age-induced increase of leptin mRNA abundance and serum leptin
      concentration and the age-induced suppression of FAS gene expression in the same
      tissue was observed. This suggests that the changes of FAS gene expression occur
      in response to serum leptin concentration and that in mature rats the high level
      of ob gene expression and consequently the high leptin concentration protect the
      white adipose tissue cells against fat overload by two independent mechanisms:
      (a) preventing an increase of food intake through the leptin action on the
      hypothalamus; (b) inhibiting FAS gene expression and consequently decreasing the
      rate of lipogenesis.

PMID- 11514239
TI  - Excitability of human axons.
AB  - The excitability of human axons can be studied reliably using the technique of
      threshold tracking, which allows the strength of a test stimulus to be adjusted
      by computer to activate a defined fraction of the maximal nerve or muscle action
      potential. The stimulus current that just evokes the target response is
      considered the "threshold" for that response. More useful than the resting
      threshold are other indices of axonal excitability derived from pairs of
      threshold measurements, such as refractoriness, supernormality, strength-duration
      time constant and "threshold electrotonus" (i.e. the changes in threshold
      produced by long-lasting depolarizing or hyperpolarizing current pulses). Each of
      these measurements depends on membrane potential and on other biophysical
      properties of the axons. Together they can provide new information about the
      pathophysiology underlying abnormalities in excitability in neuropathy.

PMID- 11514240
TI  - Electrophysiologic studies in critical illness associated weakness: myopathy or
      neuropathy--a reappraisal.
AB  - OBJECTIVE: Unexplained weakness in critically ill patients is recognized with
      increasing frequency. However, it is debated whether the condition is a
      peripheral neuropathy or a myopathy. Diagnostic difficulties can arise from
      multiple sources that are not generally a factor in other neuromuscular
      conditions. Conventional electrodiagnostic techniques may provide only non
      specific data, clinical examination is often hampered, and muscle biopsy is not a
      practical screening tool. METHOD: To improve diagnostic yield, we studied 22
      consecutive patients with critical illness associated weakness with additional
      electrodiagnostic techniques, including direct muscle stimulation, quantitative
      electromyography, and motor unit number estimation. RESULTS: The applied
      techniques supported an underlying myopathy in all the patients examined. The
      diagnosis was confirmed by muscle biopsy in 9 patients. Additional lesser
      features of neuropathy were concomitantly present in one patient who also
      underwent sural nerve biopsy. CONCLUSIONS: The study suggests that myopathy is
      much more common than polyneuropathy in critical illness. Suspicion of this
      entity should be high in this setting even without exposure to corticosteroids or
      non-depolarizing blocking agents.

PMID- 11514241
TI  - Regularity of force tremor in Parkinson's disease.
AB  - OBJECTIVES: The study examines the time-dependent structure of force tremor to
      investigate two hypotheses: (1), the regularity of tremor can help in
      discriminating normal aging from that of Parkinson's disease (PD); and (2), there
      is increased tremor regularity with increases in the severity of PD. METHODS:
      Eight young (21-29 years), eight elderly (68-80 years), and eight PD (68-80
      years) subjects produced constant grip force at 5, 25 and 50% of their maximal
      voluntary contraction by squeezing two load cells with their index finger and
      thumb under a vision and no vision condition. Spectral analysis and approximate
      entropy (ApEn) were used, respectively, to analyze the frequency and time
      dependent structure of tremor. RESULTS: The analyses showed that there were no
      differences in the amplitude and modal frequency of force tremor between groups.
      The ApEn was significantly lower in the PD group compared with the controls. For
      the PD group, the linear relations between the total scores taken from the
      Unified Parkinson's Disease Rating Scale-motor section and the dependent
      variables were r(2)=0.71 (P<0.01) for ApEn, r(2)=0.20 (P>0.05) for the modal
      frequency, and r(2)=0.23 (P>0.05) for the standard deviation. Surrogate analyses
      revealed that the time-dependent structure of tremor provided additional
      information beyond that of amplitude and modal frequency analyses. CONCLUSIONS:
      These findings indicate that tremor analyses should not be limited to just the
      frequency and amplitude of the oscillation, and that the time-dependent structure
      of tremor is useful in differentiating tremor in healthy people from those with
      PD. The hypothesis that more regular tremor in PD is due to a loss of multiple
      neuronal oscillators contributing to the tremor output is discussed.

PMID- 11514242
TI  - Intracortical inhibition and facilitation in human facial motor area: difference
      between upper and lower facial area.
AB  - OBJECTIVE: To investigate the intracortical inhibitory and excitatory systems in
      the motor cortical representation of upper and lower facial muscles. METHODS:
      Paired-pulse transcranial magnetic stimulation (TMS) was applied to 7 healthy
      volunteers, with the interstimulus interval (ISI) between the conditioning
      stimulus (CS) and test stimulus, varied from 1 to 20 ms. CS was set at 90% of
      motor threshold. Muscle evoked potentials (MEPs) were recorded from first dorsal
      interosseus (FDI), orbicularis oculi (o. oculi) and mentalis muscles. RESULT: TMS
      evoked MEPs in o. oculi on both ipsi- and contralateral sides in all subjects. In
      the paired-pulse study, MEP amplitude in the mentalis decreased at short ISIs of
      1-3 ms, followed by increases at 12-20 ms. These effects were similar to those in
      the FDI. O. oculi did not show a distinct inhibitory period at short ISIs and
      facilitation at long ISIs was detected but was significantly less than in FDI and
      mentalis. In o. oculi, there was no significant difference between the effects of
      ipsilateral and contralateral CS on the MEPs. CONCLUSION: The bi-hemispheric
      control of volitional movement and the modulation from brainstem projections
      appear to markedly influence intracortical inhibitory and excitatory systems in
      the motor cortical representation of o. oculi.

PMID- 11514243
TI  - Enhanced associated movements in the contralateral limbs elicited by brisk
      voluntary contraction in choreic disorders.
AB  - OBJECTIVES: To study the deficit of inhibition of excessive motor drive generated
      in the central nervous system in chorea. METHODS: Identical associated movements
      in the contralateral limb elicited by rapid hand squeezing were measured in 6
      patients with Huntington's disease, 7 patients with peak-dose dyskinesia, 10
      patients with Parkinson's disease, 8 patients with spinocerebellar degeneration
      and in 8 normal subjects. The intensity of associated movements was assessed by
      the EMG amplitude ratio of associated contractions to active contractions.
      RESULTS: The associated movement ratios were larger in Huntington's disease and
      peak-dose dyskinesia as compared to other groups. The ratios in akinetic "off"
      phase were smaller than those in dyskinetic "on" phase in all peak-dose
      dyskinesia patients. CONCLUSIONS: Enhanced associated movements support a
      possible common mechanism that chorea may result from failure in inhibition of
      phasic neural activity pathologically generated in the brain.

PMID- 11514244
TI  - Distinct multi-joint control strategies in spastic diplegia associated with
      prematurity or Angelman syndrome.
AB  - Spastic diplegia is commonly due to periventricular leucomalacia associated with
      premature birth. It is also a feature of Angelman syndrome (AS), a neurogenetic
      disorder with developmental delay, absent speech and mirthful behaviour. We
      studied the kinematics and kinetics of the squatting movement and associated
      electromyographic (EMG) activities in 20 children with spastic diplegia
      associated with periventricular leucomalacia (SDPL) or AS and 18 unimpaired
      children. While movement of normal subjects consisted of vertical translation of
      most body segments, the movement of SDPL children was operated around the fixed
      knee with backward shift of the hip, and AS children performed a forward flexion
      of the trunk over the thigh. Trunk stability was correlated with movement
      velocity in both pathological groups. In normal subjects, anticipatory EMG
      pattern consisted of silencing of hamstring muscle tonic activity prior to
      movement onset. This deactivation was not present in spastic diplegia. In SDPL,
      anticipatory overactivation of ankle joint actuators was recorded and tonic co
      contraction persisted throughout the movement. In AS, rhythmic EMG bursting was
      seen during the movement. Shoulder, hip and knee trajectories in the sagittal
      plane showed marked within-group stereotypies in orientation, shape and length.
      The patterns in both pathological groups were therefore distinctive. We speculate
      that they reflect corticospinal impairment in SDPL and combined corticospinal and
      cerebellar dysfunction in AS.

PMID- 11514245
TI  - Electromyographic differentiation of tremors.
AB  - OBJECTIVE: The aim of this study was to explore the opportunity for
      differentiation of tremors on the basis of the electromyographic examination.
      METHODS: We report data from 525 patients with different types of tremor included
      in this study. Two hundred and twenty patients with essential tremor, 110
      patients with Parkinson's disease, 24 patients with midbrain tremor, 22 patients
      with cerebellar tremor, 120 patients with enhanced physiological tremor due to
      anxiety, and 29 patients with psychogenic tremor participated in the study. A
      detailed neurological and electromyographic examination was performed. The tremor
      was studied in all limbs positions. Surface electromyographic recordings of the
      most involved body part were performed to all patients. RESULTS: According to the
      electromyographic examination all patients were divided to two groups: Patients
      with synchronous tremor and patients with alternating tremor in the antagonist
      muscles. The comparisons were performed only between the patients with tremor
      caused by different etiology within the group of synchronous or alternating
      tremor. The group of tremors with synchronous pattern included the patients with
      essential tremor type A (with synchronous activity), cerebellar, and enhanced
      physiological tremor. The group of tremors with alternating pattern included
      patients with Parkinsonian tremor, essential tremor type B (with alternating
      activity), rubral, and psychogenic tremors. Our results revealed that
      electromyographic examination of tremor pattern, frequency, amplitude, and burst
      duration is useful for tremor differentiation. CONCLUSION: The electromyographic
      examination may serve as a tool for differentiation of tremors.

PMID- 11514246
TI  - Inhibition of motor system excitability at cortical and spinal level by tonic
      muscle pain.
AB  - OBJECTIVE: To assess whether the motor system excitability can be modified by
      experimental tonic pain induced either in muscles or in subcutis. METHODS:
      Transcranial magnetic stimulation of the left primary motor cortex was used to
      record motor evoked potentials (MEPs) from the right abductor digiti minimi (ADM)
      muscle. Recordings were made before, during and after experimental pain induced
      by (1) injection of hypertonic (5%) saline into the right ADM, the right first
      dorsal interosseum (FDI) and the left ADM muscles, and (2) injection of
      hypertonic saline in the subcutaneous region of the right ADM. Both MEPs and H
      reflex were recorded also from the right flexor carpi radialis (FCR) before,
      during and after muscle pain. RESULTS: MEPs recorded from the ADM muscle were
      significantly reduced in amplitude during pain induced in the right ADM and right
      FDI muscles, but not during pain in the left ADM muscle or during subcutaneous
      pain. This inhibitory effect was observed during the peak-pain and persisted also
      after the disappearance of the pain sensation. In the FCR muscle, the MEP
      inhibition was observed during the peak-pain, while a significant reduction of
      the H-reflex's amplitude was observed starting 1 min after the peak-pain.
      CONCLUSIONS: Tonic muscle pain can inhibit the motor system. The motor cortex
      inhibition observed at an early phase is followed by a reduction of the
      excitability of both cortical and spinal motoneurones.

PMID- 11514247
TI  - Steep early negative slopes can be demonstrated in pre-movement
      bereitschaftspotential.
AB  - OBJECTIVES: The study presents data suggesting that the classic
      bereitschaftspotential hides in its early component (BP1) steep increases of
      negativity which precede the movement at varying intervals in repeated trials.
      METHODS: In 12 volunteers, surface EEG from Fz, Cz, C3, C4, and Pz electrodes and
      EMG from the flexor digitorum communis were recorded during self-paced wrist
      flexions. Two hundred trials were collected from each subject. The single trials
      were grouped for averaging in two different ways. In the first one, single trials
      for each subject were used to create individual averages. In the second, all
      single trials were divided into groups according to the point in time of small
      steep negative shift from the baseline detected on sweeps before the movement and
      time group averages were created. The identification of small shifts was based on
      the comparison of calculated mean amplitudes in the first and the second half of
      the 1 s time window moved along the time axis. RESULTS: The small negative shifts
      were identified in 97.2% of analyzed records. In each subject, their position on
      the time axis varied considerably. Individual averages exhibited the
      characteristics of classical readiness potential, i.e. slow early component,
      steep late component, laterality over motor cortices. On the other hand, all time
      group averages (26) displayed an early steep negative shift followed by plateau
      which, about 0.5 s before the movement, gave rise to the second, late steep
      negative shift. The slope values calculated in the definite segments of averaged
      curves were used as a measure of the amplitude of these shifts over various brain
      areas. MANOVA showed a significant effect of the electrode position both in the
      case of early slopes (F(4,115)=9.7; P<0.000) and in the case of late slopes
      (F(4,115)=22.5; P<0.000). In both cases, the largest value was demonstrated under
      Cz electrode. In contrast to the late slopes, the values of early slopes did not
      exhibit laterality and suggested greater importance of pre-frontal regions in
      their formation. CONCLUSION: We have suggested that the formation of steep early
      negative shifts from the baseline in time group averages was due to
      synchronization of a mental process which, under classical averaging procedure,
      was dispersed uniformly throughout the pre-movement period.

PMID- 11514248
TI  - Response to the first stimulus determines reduced auditory evoked response
      suppression in schizophrenia: single trials analysis using MEG.
AB  - OBJECTIVE: Reduced auditory evoked response (AER) suppression in a paired
      stimulus paradigm may index genetic liability for schizophrenia. In most
      published studies of AER suppression, scores are based on data averaged over
      numerous stimulus presentations and recorded from few channels. It is unclear
      whether averaged data are equally representative of single trial responses in
      normal and schizophrenia subjects. In the present report, we used 148 channel
      magnetoencephalography to investigate grand-average and single trial responses on
      AER suppression. METHODS: The typical paired-stimulus paradigm was used to evoke
      time-locked AERs from 20 normal and 20 schizophrenia patients. Gamma band
      response (GBR) and low frequency response (LFR) characteristics were measured on
      grand-averaged and single trial data. Generalized eigenvalue decomposition was
      used to reduce the multiple channel information to a vector that accounted for
      the most AER variance for the GBR and LFR. RESULTS: Group performances on grand
      average and single trials were similar. A remarkable difference, which replicates
      previous studies, was that schizophrenia subjects had smaller LFR amplitudes in
      response to the first stimulus than normal. CONCLUSIONS: These findings are
      inconsistent with the "poor suppression" theory often used to explain
      schizophrenia-normal group differences when using the paired-stimulus paradigm.

PMID- 11514249
TI  - Response priming in a go/nogo task: do we have to explain the go/nogo N2 effect
      in terms of response activation instead of inhibition?
AB  - OBJECTIVES: In the present study, we examined the effects of response priming on
      the event-related potentials (ERPs) evoked by target stimuli in a go/nogo task.
      METHODS: In each trial, subjects were presented a cue and a target stimulus. The
      cue informed subjects about the following target in that trial, and therefore,
      also about the kind of response (right-hand response, left-hand response, no
      overt response) potentially to be given in that trial. RESULTS: The traditional
      N2 and P3 go/nogo effects were replicated: the ERPs to nogo targets were negative
      compared to the ERPs evoked by go targets in the N2 latency range at frontal
      electrode sites, and the nogo P3s were more anteriorly distributed than the go
      P3s. Comparing the ERPs evoked by nogo targets, we found the P3, but not the N2,
      to be modulated by response priming. CONCLUSIONS: These results seem to indicate
      that the P3, but not the N2, is associated with response inhibition, or with an
      evaluation/decision process with regard to the expected and/or given response. It
      could be speculated that the traditional go/nogo N2 effect has to be explained in
      terms of response activation instead of response inhibition.

PMID- 11514250
TI  - Transcranial magnetic stimulation of left prefrontal cortex impairs working
      memory.
AB  - OBJECTIVES: Several lines of evidence suggest that the prefrontal cortex is
      involved in working memory. Our goal was to determine whether transient
      functional disruption of the dorsolateral prefrontal cortex (DLPFC) would impair
      performance in a sequential-letter working memory task. METHODS: Subjects were
      shown sequences of letters and asked to state whether the letter just displayed
      was the same as the one presented 3-back. Single-pulse transcranial magnetic
      stimulation (TMS) was applied over the DLPFC between letter presentations.
      RESULTS: TMS applied over the left DLPFC resulted in increased errors relative to
      no TMS controls. TMS over the right DLPFC did not alter working memory
      performance. CONCLUSION: Our results indicate that the left prefrontal cortex has
      a crucial role in at least one type of working memory.

PMID- 11514251
TI  - Button-pressing affects P300 amplitude and scalp topography.
AB  - BACKGROUND: Scant and equivocal research exists examining the effects of button
      pressing on P300. Button-pressing may decrease P300 latency and amplitude. The
      melding of motor potentials and P300 may also confound studies of P300
      topography, such as studies of temporal scalp-area asymmetries in schizophrenia.
      METHOD: P300 was measured on button-press and silent-count tasks in control
      subjects. An estimate of motor activity was constructed from a simple reaction
      time task, with reaction times matched to the button-press task. The motor
      estimate was subtracted from the button-press P300 to assess Kok's (1988)
      additive model. Lastly, lateral P300 from schizophrenia patients was compared
      with each condition's P300. RESULTS: P300 was smaller and its topography
      different in the button-pressing task relative to silent-counting. The motor
      correction procedure generated a P300 with normal topography. Comparison of the
      button-press P300 in controls to the silent-count P300 in schizophrenia patients
      reduced a significant lateral asymmetry to trend level. This asymmetry was
      significant after the correction procedure. CONCLUSIONS: Button-pressing
      generates smaller P300 than silent-counting. Also, P300 topography in button
      pressing tasks is confounded by motor potentials. The distortion can be corrected
      with a motor potential estimate. Motor potentials can occlude differences in P300
      topography between groups.

PMID- 11514252
TI  - Neuromagnetic activity in alpha and beta bands reflect learning-induced increases
      in coordinative stability.
AB  - OBJECTIVE: To investigate how learning induced increases in stability on a
      syncopation task are manifest in the dynamics of cortical activity. METHOD:
      Magnetoencephalography was recorded from 143 sensors (CTF Systems, Inc). A pre
      training procedure determined the critical frequency (F(c)) for each subject
      (n=4). Subjects either syncopated or synchronized to a metronome that increased
      in frequency from 1.2 to 3.0 Hz in 0.2 Hz steps. The F(c) was the point at which
      subjects spontaneously switched from syncopation to synchronization. Subjects
      then underwent 100 training trials (with feedback) at F(c). Following the
      learning phase the pre-training procedure was repeated. RESULTS: An increase in
      the F(c) occurred indicating that practice improved the stability of syncopation.
      The transition delay was also observed in the phase of the time-averaged signal
      in sensors over the contralateral sensorimotor area and in power analysis in the
      8-12 Hz and 18-24 Hz frequency bands. Initially, reduced power was observed
      bilaterally during syncopation compared to synchronization. Following training,
      these differences were reduced or eliminated. CONCLUSION: Pre-training power
      differences can be explained by the greater difficulty of the syncopation task.
      The reduction in power differences following training suggests that at the
      cortical level, syncopation became more similar to synchronization possibly
      reflecting a decrease in task and/or attention demands.

PMID- 11514253
TI  - The use of phase in the detection of auditory steady-state responses.
AB  - OBJECTIVE: To investigate how phase measurements might facilitate the detection
      of auditory steady-state responses. METHODS: Multiple steady-state responses were
      evoked by auditory stimuli modulated at rates between 78 and 95 Hz and with
      intensities between 50 and 0 dB SPL. The responses were evaluated in 20 subjects
      after 1, 2, 4, and 6 min. The responses were analyzed in the frequency domain
      using 4 different detection protocols: (1) phase-coherence, (2) phase-weighted
      coherence, (3) F test for hidden periodicity, and (4) phase-weighted t test. The
      phase-weighted measurements were either based on the mean phase of a group of
      normal subjects or derived for each subject from the phase of the response at
      higher intensities. RESULTS: Detection protocols based on both phase and
      amplitude (F test and phase-weighted t test) were more effective than those based
      on phase alone (phase coherence and phase-weighted coherence) although the
      difference was small. Protocols using phase-weighting were more effective than
      those without phase-weighting. The lowest thresholds for the steady-state
      responses were obtained using the phase-weighted t test. CONCLUSION: Threshold
      detection can be improved by weighting the detection protocols toward an expected
      phase, provided that the expected phase can be reliably predicted.

PMID- 11514254
TI  - The mismatch negativity as an index of temporal processing in audition.
AB  - OBJECTIVES: The relation of the mismatch negativity (MMN) elicitation with
      behavioral stimulus discrimination as well as the replicability of the MMN was
      evaluated for intervals between paired tones. METHODS: The MMN, obtained in a
      passive oddball paradigm in two sessions separated by 4-21 days and behavioral
      responses (button presses to target stimuli) in a separate session were recorded
      from 10 adult healthy subjects. The standard stimulus (P=0.79) was a tone pair
      separated by a 120 ms silent inter-stimulus interval (ISI) and the deviant
      stimuli were tone pairs with an ISI of 100, 60, and 20 ms (P=0.07 for each).
      RESULTS: The 20 and 60 ms ISI deviant tone pairs elicited a significant MMN
      during both recording sessions and they were also behaviorally discriminated,
      whereas neither did the 100 ms ISI deviant pair elicit significant MMN nor was it
      behaviorally discriminated. Furthermore, there was a significant correlation
      between the MMN and reaction times to the 20 and 60 ms ISI deviant pairs. The 20
      ms ISI deviant stimulus elicited highly replicable MMNs (r=0.75), whereas the
      less well discriminated 60 ms ISI deviant pair did not (r=0.60). CONCLUSIONS: The
      MMN reflects discrimination accuracy of temporal sound intervals. Furthermore,
      when the physical difference between the standard and deviant tone pair in the
      temporal domain is large, it is elicited with high reliability.

PMID- 11514255
TI  - Identification of principal components in cortical evoked potentials by brief
      surface cooling.
AB  - OBJECTIVES: The evoked potential recorded by a single electrode in rat's barrel
      cortex after whisker stimulation was shown to be composed of two main principal
      components shifted in time by about 3 ms. The purpose of this study was to verify
      the hypothesis that these components represent activity of supra- and
      infragranular pyramidal cell classes. RESULTS: Our results show that a brief
      cooling pulse applied to the cortical surface abolishes the shorter latency
      component, which may therefore be attributed to the response of supragranular
      pyramidal cells. CONCLUSIONS: The longer latency principal component, which
      disappears only with strong cooling pulses, is proposed to represent postsynaptic
      activity of infragranular pyramidal neurons.

PMID- 11514256
TI  - BIPLEDs in akinetic mutism caused by bilateral anterior cerebral artery
      infarction.
AB  - INTRODUCTION: Akinetic mutism is described as a result of many disorders.
      Bilateral infarction of the anterior cerebral artery (ACA) territory is reported
      rarely, however, often leading to akinetic mutism. CASE REPORT: We report a 70
      year-old man with akinetic mutism due to bilateral ACA infarction.
      Electroencephalography, 24h after admission, showed bilateral independent
      periodic lateralized epileptiform discharges (BIPLEDs) in the frontal region and
      diffuse theta and polymorphic delta activity. DISCUSSION: Postanoxic
      encephalopathy, central nervous system infection and chronic seizure disorders
      are the major causes of BIPLEDs. However, BIPLEDs may occur in bilateral ACA
      territory infarction.

PMID- 11514257
TI  - Estimation of the EEG power spectrum using MRI T(2) relaxation time in traumatic
      brain injury.
AB  - OBJECTIVES: To study the relationship between magnetic resonance imaging (MRI)
      T(2) relaxation time and the power spectrum of the electroencephalogram (EEG) in
      long-term follow up of traumatic brain injury. METHODS: Nineteen channel
      quantitative electroencephalograms or qEEG, tests of cognitive function and
      quantitative MRI T(2) relaxation times (qMRI) were measured in 18 mild to severe
      closed head injured outpatients 2 months to 4.6 years after injury and 11 normal
      controls. MRI T(2) and the Laplacian of T(2) were then correlated with the power
      spectrum of the scalp electrical potentials and current source densities of the
      qEEG. RESULTS: qEEG and qMRI T(2) were related by a frequency tuning with maxima
      in the alpha (8-12Hz) and the lower EEG frequencies (0.5-5Hz), which varied as a
      function of spatial location. The Laplacian of T(2) acted like a spatial-temporal
      "lens" by increasing the spatial-temporal resolution of correlation between 3
      dimensional T(2) and the ear referenced alert but resting spontaneous qEEG.
      CONCLUSIONS: The severity of traumatic brain injury can be modeled by a linear
      transfer function that relates the molecular qMRI to qEEG resonant frequencies.

PMID- 11514258
TI  - Neural networks involving the medial temporal structures in temporal lobe
      epilepsy.
AB  - OBJECTIVES: In a previous study using the averaged coherence technique to study
      interactions between medial/limbic and lateral/neocortical regions, we observed
      that epileptogenic networks in temporal lobe epilepsy seizures (TLES) could be
      divided into 4 subtypes, i.e. medial (M), medial-lateral (ML), lateral-medial
      (LM), and lateral (L). In the ML and LM subtypes, medial structures and the
      anterior temporal neocortex are co-activated at the onset of seizures. However,
      using this approach, we were unable to determine the direction of coupling and
      may have overlooked non-linear variations in interdependency. The purpose of the
      present study using non-linear regression for analysis of
      stereoelectroencephalographic (SEEG) signal pairs was to measure the degree and
      direction of coupling between medial and neocortical areas during TLES in
      patients with the M, ML, and LM subtypes. METHODS: Eighteen patients with drug
      resistant TLEs who underwent SEEG recording were studied. We used a non-linear
      correlation method as a measure of the degree and the direction of coupling on
      SEEG signal pairs. Patients with pure lateral TLEs were not studied. We analyzed
      the functional coupling between 3 regions of the temporal lobe: the anterior
      temporal neocortex, the amygdala, and the anterior hippocampus. A physiological
      model of EEG generation was used to validate the non-linear quantification method
      and assess its applicability to real SEEG signals. RESULTS: Results are first
      based on a physiological model of EEG data in which both degree and direction of
      coupling are explicitly represented, thus allowing construction of the neural
      systems inside which causality relationships are controlled and generation of
      multichannel EEG signals from these systems. These signals provide an objective
      way of studying the performance of non-linear regression analysis on real
      signals. In medial networks (10 patients), the ictal discharge is limited to the
      medial limbic structures and may propagate secondarily to the cortex. Quantified
      results demonstrated no significant coupling between medial and lateral
      structures at the beginning of the seizures. Conversely, almost constant
      unidirectional or bidirectional coupling was observed between hippocampus and
      amygdala. In medial-lateral (5 patients) and lateral-medial (3 patients)
      networks, the initial ictal discharge includes both limbic and neocortical
      regions. A rapid "tonic" discharge is observed over the temporal neocortex at the
      onset of seizure. Quantitative analysis showed an initial increase in the non
      linear correlation coefficient between neocortex and medial structures.
      Quantification of the coupling direction demonstrated influence of medial over
      lateral structures (medial-lateral) or of the lateral neocortex over medial
      structures (lateral-medial). CONCLUSIONS: These results confirm the existence of
      several generic and organized networks involving the medial structures during TLE
      seizures.

PMID- 11514259
TI  - Cortical current density reconstruction of interictal epileptiform activity in
      temporal lobe epilepsy.
AB  - OBJECTIVE: To investigate the value of cortical current density (CCD)
      reconstruction in localizing intracranial generators of interictal epileptiform
      activity in mesial and lateral temporal lobe epilepsy (TLE). METHODS: Non-linear
      minimum L(1)-norm CCD reconstruction (with current sources restricted to the
      individual cortical surface and a realistic boundary element method (BEM) head
      model) was used to localize and to study the propagation of interictal
      epileptiform EEG activity in 13 pre-surgical patients with TLE. RESULTS: In all
      but one patient with mesial temporal lesions, an initial activation maximum
      corresponding to the ascending part of averaged sharp waves was found in the
      ipsilateral anterior basolateral temporal lobe, mostly extending up to the
      affected mesial structures whose resection rendered the patients seizure-free. In
      all 3 patients with lateral temporal lesions, the activation was initially
      confined to temporal neocortex immediately adjacent to the epileptogenic lesion.
      Towards the peak of sharp waves, two patients showed a propagation of interictal
      activity to anterior and posterior and partly contralateral temporal regions. A
      conventional EEG analysis based on amplitude maxima or phase reversal would have
      missed the initial onset zone. CONCLUSIONS: The findings demonstrate that CCD
      reconstruction can be a valuable additional non-invasive component in the
      multimodal pre-surgical evaluation of epilepsy patients.

PMID- 11514260
TI  - The effect of the skull on event-related P300.
AB  - OBJECTIVES: Event-related potentials (EP) indicate neuronal processes with a high
      temporal resolution, while functional magnetic resonance imaging (fMRI) has a
      high spatial distribution. Information from both techniques may complement each
      other. However, this combination is fraught with difficulty because of a possible
      interference of the skull or the scalp with scalp-recorded EP. The aim of the
      present study was to investigate this influence of skull and scalp thicknesses on
      event-related P300 potentials. METHODS: Thirty healthy controls were examined
      using an auditory evoked P300 elicited by a standard oddball paradigm. Skull and
      scalp thicknesses were determined using coronal T2-weighted magnetic resonance
      imaging (MRI). RESULTS: P3b-amplitudes were significantly correlated with temporo
      parietal skull thickness (r=-0.42; P=0.021; regression slope of -1.14 microV/mm
      skull thickness), whereas scalp had no influence on P300. The amplitude of the
      more frontal subcomponent P3a was not related to frontal skull thickness.
      CONCLUSIONS: Therefore, the utility of P300 as a research tool can be enhanced
      when adjustment for skull thickness is made.

PMID- 11514261
TI  - The influence of electrode location errors on EEG dipole source localization with
      a realistic head model.
AB  - OBJECTIVES: Inaccurate information about the electrode locations on the scalp
      will introduce errors in electroencephalogram dipole source localization results.
      The present study uses computer simulations to evaluate such errors in a
      realistic head model and in the context of noise. METHODS: A realistic head model
      was constructed from magnetic resonance imaging scans and 29 electrodes placed on
      the head according to the 10-20 International System. Twenty sets of electrode
      displacements, with a mean value of 5 mm, were generated and 200 single dipoles
      evenly located in the brain were used as test sources. The boundary element
      method was employed for the forward calculation and dipole fitting was carried
      out at different noise levels. RESULTS: For a noise-free signal, the source
      localization error due to electrode misplacement is about 5 mm, whereas it is
      about 2 mm for normal noisy signals. CONCLUSIONS: For realistic head models,
      dipole estimation error due to electrode misplacement is negligible compared with
      errors caused by noise.

PMID- 11514262
TI  - Vascular endothelial dysfunction: does tetrahydrobiopterin play a role?
AB  - Tetrahydrobiopterin is one of the most potent naturally occurring reducing agents
      and an essential cofactor required for enzymatic activity of nitric oxide
      synthase (NOS). The exact role of tetrahydrobiopterin in the control of NOS
      catalytic activity is not completely understood. Existing evidence suggests that
      it can act as allosteric and redox cofactors. Suboptimal concentration of
      tetrahydrobiopterin reduces formation of nitric oxide and favors "uncoupling" of
      NOS leading to NOS-mediated reduction of oxygen and formation of superoxide
      anions and hydrogen peroxide. Recent findings suggest that accelerated catabolism
      of tetrahydrobiopterin in arteries exposed to oxidative stress may contribute to
      pathogenesis of endothelial dysfunction present in arteries exposed to
      hypertension, hypercholesterolemia, diabetes, smoking, and ischemia-reperfusion.
      Beneficial effects of acute and chronic tetrahydrobiopterin supplementation on
      endothelial function have been reported in experimental animals and humans.
      Furthermore, it appears that beneficial effects of some antioxidants (e.g.,
      vitamin C) on vascular function could be mediated via increased intracellular
      concentration of tetrahydrobiopterin. In this review, the potential role of
      tetrahydrobiopterin in the pathogenesis of vascular endothelial dysfunction and
      mechanisms underlying beneficial vascular effects of tetrahydrobiopterin will be
      discussed.

PMID- 11514263
TI  - Myocardial and interstitial matrix metalloproteinase activity after acute
      myocardial infarction in pigs.
AB  - A structural event during the evolution of a myocardial infarction (MI) is left
      ventricular (LV) remodeling. The mechanisms that contribute to early changes in
      LV myocardial remodeling in the post-MI period remain poorly understood. Matrix
      metalloproteinases (MMPs) contribute to tissue remodeling in several disease
      states. Whether and to what degree MMP activation occurs within the myocardial
      interstitium after acute MI remains to be determined. Adult pigs (n = 15) were
      instrumented to measure regional myocardial function and interstitial MMP levels
      within regions served by the circumflex and left anterior descending arteries.
      Regional function was measured by sonomicrometry, and interstitial MMP levels
      were determined by selective microdialysis and zymography as well as by MMP
      interstitial fluorogenic activity. Measurements were performed at baseline and
      sequentially for up to 3 h after ligation of the obtuse marginals of the
      circumflex artery. Regional fractional shortening fell by over 50% in the MI
      region but remained unchanged in the remote region after coronary occlusion.
      Release of soluble MMPs, as revealed by zymographic activity of myocardial
      interstitial samples, increased by 2 h post-MI. The increased zymographic
      activity after MI was consistent with MMP-9. Myocardial interstitial MMP
      fluorogenic activity became detectable within the ischemic region as early as 10
      min after coronary occlusion and significantly increased after 1 h post-MI. MMP
      fluorogenic activity remained unchanged from baseline values in the remote
      region. The present study demonstrated that myocardial MMP activation can occur
      within the MI region in the absence of reperfusion. These unique results suggest
      that MMP release and activation occurs within the ischemic myocardial
      interstitium in the early post-MI period.

PMID- 11514264
TI  - Blunted nitric oxide-mediated inhibition of renal nerve discharge within PVN of
      rats with heart failure.
AB  - We have demonstrated a decreased neuronal nitric oxide (NO) synthase (nNOS)
      message in the hypothalamus of rats with heart failure (HF). Subsequently, we
      have demonstrated that NADPH diaphorase (a commonly used marker for nNOS
      activity) positive neurons are decreased in paraventricular nucleus (PVN) of rats
      with coronary artery ligation model of HF. The goal of the present study was to
      examine the influence of endogenous NO within the PVN on renal sympathetic nerve
      discharge (RSND) during HF. In alpha-chloralose- and urethane-anesthetized rats,
      an inhibitor of NO synthase, N(G)-monomethyl-L-arginine (L-NMMA) microinjected
      into the PVN (50, 100, and 200 pmol in 50-200 nl) produced a dose-dependent
      increase in RSND, blood pressure, and heart rate in control and HF rats. These
      responses were attenuated in rats with HF compared with control rats. On the
      other hand, the NO agonist, sodium nitroprusside, microinjected in PVN produced a
      dose-dependent decrease in RSND and blood pressure in control and HF rats. These
      responses were less in rats with HF compared with control rats. These data
      suggest that the endogenous NO-mediated effect within the PVN of HF rats is less
      potent in suppressing RSND compared with control rats. These data support the
      conclusion that the NO system within the PVN involved in controlling autonomic
      outflow is altered during HF and may contribute to the elevated levels of renal
      sympathoexcitation commonly observed in HF.

PMID- 11514265
TI  - Effects of chronic estrogen-receptor blockade on ovine perinatal pulmonary
      circulation.
AB  - Prolonged infusions of 17beta-estradiol reduce fetal pulmonary vascular
      resistance (PVR), but the effects of endogenous estrogens in the fetal pulmonary
      circulation are unknown. To test the hypothesis that endogenous estrogen promotes
      pulmonary vasodilation at birth, we studied the hemodynamic effects of prolonged
      estrogen-receptor blockade during late gestation and at birth in fetal lambs. We
      treated chronically prepared fetal lambs with ICI-182,780 (ICI, a specific
      estrogen-receptor blocker, n = 5) or 1% DMSO (CTRL, n = 5) for 7 days and then
      measured pulmonary hemodynamic responses to ventilation with low- and high
      fraction inspired oxygen (FI(O(2))). Treatment with ICI did not change basal
      fetal PVR or arterial blood gas tensions. However, treatment with ICI abolished
      the vasodilator response to ventilation with low FI(O(2)) [change in PVR -30 +/-
      6% (CTRL) vs. +10 +/- 13%, (ICI), P < 0.05] without reducing the vasodilator
      response to ventilation with high FI(O(2)) [change in PVR, -73 +/- 3% (CTRL) vs. 
      77 +/- 4%, (ICI); P = not significant]. ICI treatment reduced prostacyclin
      synthase (PGIS) expression by 33% (P < 0.05) without altering expression of
      endothelial nitric oxide synthase or cyclooxygenase-1 and -2. In situ
      hybridization and immunohistochemistry revealed that PGIS is predominantly
      expressed in the airway epithelium of late gestation fetal lambs. We conclude
      that prolonged estrogen-receptor blockade inhibits the pulmonary vasodilator
      response at birth and that this effect may be mediated by downregulation of PGIS.
      We speculate that estrogen exposure during late gestation prepares the pulmonary
      circulation for postnatal adaptation.

PMID- 11514266
TI  - Structural adaptation of microvascular networks: functional roles of adaptive
      responses.
AB  - Terminal vascular beds continually adapt to changing demands. A theoretical model
      is used to simulate structural diameter changes in response to hemodynamic and
      metabolic stimuli in microvascular networks. Increased wall shear stress and
      decreased intravascular pressure are assumed to stimulate diameter increase.
      Intravascular partial pressure of oxygen (PO(2)) is estimated for each segment.
      Decreasing PO(2) is assumed to generate a metabolic stimulus for diameter
      increase, which acts locally, upstream via conduction along vessel walls, and
      downstream via metabolite convection. By adjusting the sensitivities to these
      stimuli, good agreement is achieved between predicted network characteristics and
      experimental data from microvascular networks in rat mesentery. Reduced pressure
      sensitivity leads to increased capillary pressure with reduced viscous energy
      dissipation and little change in tissue oxygenation. Dissipation decreases
      strongly with decreased metabolic response. Below a threshold level of metabolic
      response flow shifts to shorter pathways through the network, and oxygen supply
      efficiency decreases sharply. In summary, the distribution of vessel diameters
      generated by the simulated adaptive process allows the network to meet the
      functional demands of tissue while avoiding excessive viscous energy dissipation.

PMID- 11514267
TI  - Hemodynamic effects elicited by microinjection of glutamatergic agonists into NTS
      of conscious rats.
AB  - In this study, we characterized the arterial pressure, heart rate, and regional
      vascular conductance responses elicited by unilateral microinjection of
      ionotropic glutamatergic agonists N-methyl-D-aspartic acid (NMDA and non-NMDA)
      into the nucleus of tractus solitarius (NTS) of conscious rats. Microinjections
      of NMDA and S-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)
      caused changes in mean arterial pressure (MAP). Lower doses elicited decreases in
      MAP, whereas higher doses elicited biphasic responses (decreases followed by
      increases). Both agonists induced bradycardia and elicited dose-dependent
      vasoconstriction in the renal, mesenteric, and hindquarter beds. AMPA elicited
      delayed vasodilation in the hindquarter bed but NMDA did not. Bradycardia and
      initial hypotension produced by each agonist were abolished by systemic
      administration of the muscarinic antagonist methylatropine. However,
      methylatropine did not affect either the vasoconstriction or the vasodilatation.
      The contrasting hemodynamic effects produced by NMDA and AMPA could be caused by
      activation of differential subsets of NTS neurons. Preferential activation of one
      subset could produce the NMDA-related responses, whereas activation of another
      subset would elicit AMPA-related responses.

PMID- 11514269
TI  - PET(CO(2)) inversely affects MSNA response to orthostatic stress.
AB  - Arterial hypocapnia has been associated with orthostatic intolerance. Therefore,
      we tested the hypothesis that hypocapnia may be detrimental to increases in
      muscle sympathetic nerve activity (MSNA) and total peripheral resistance (TPR)
      during head-up tilt (HUT). Ventilation was increased approximately 1.5 times
      above baseline for each of three conditions, whereas end-tidal PCO(2)
      (PET(CO(2))) was clamped at normocapnic (Normo), hypercapnic (Hyper; +5 mmHg
      relative to Normo), and hypocapnic (Hypo; -5 mmHg relative to Normo) conditions.
      MSNA (microneurography), heart rate, blood pressure (BP, Finapres), and cardiac
      output (Q, Doppler) were measured continuously during supine rest and 45 degrees
      HUT. The increase in heart rate when changing from supine to HUT (P < 0.001) was
      not different across PET(CO(2)) conditions. MSNA burst frequency increased
      similarly with HUT in all conditions (P < 0.05). However, total MSNA and the
      increase in total amplitude relative to baseline (%DeltaMSNA) increased more when
      changing to HUT during Hypo compared with Hyper (P < 0.05). Both BP and Q were
      higher during Hyper than both Normo and Hypo (main effect; P < 0.05). Therefore,
      the MSNA response to HUT varied inversely with levels of PET(CO(2)). The combined
      data suggest that augmented cardiac output with hypercapnia sustained blood
      pressure during HUT leading to a diminished sympathetic response.

PMID- 11514268
TI  - TGF-beta(1) modulates NOS expression and phosphorylation of Akt/PKB in rat
      myocytes exposed to hypoxia-reoxygenation.
AB  - Myocardial hypoxia-reoxygenation (H-R) is associated with upregulation of
      inducible nitric oxide synthase (iNOS), decrease in endothelial NOS (eNOS), and
      increase in protein kinase B (PKB). Previous work also shows that transforming
      growth factor-beta(1) (TGF-beta(1)) can attenuate myocardial injury induced by H
      R. We examined the modulation of NOS and PKB expression in response to H-R by TGF
      beta(1). Myocytes from Sprague-Dawley rat hearts were cultured and exposed to
      hypoxia (95% N(2)-5% CO(2), PO(2) ~30 mmHg) for 24 h and reoxygenation (95% air
      5% CO(2)) for 3 h. Myocytes were then examined for lactate dehydrogenase (LDH)
      release, iNOS activity (conversion of L-[(3)H]arginine to L-[(3)H]citrulline),
      iNOS and eNOS expression, and PKB phosphorylation. H-R alone resulted in myocyte
      injury, upregulation of iNOS activity and expression, decrease in eNOS
      expression, and increase in PKB phosphorylation (all P < 0.05 vs. cells cultured
      in normoxic conditions). Treatment of myocytes with TGF-beta(1) (1 ng/ml)
      resulted in a reduction in LDH release, attenuation of the alterations in NOS
      expression (both iNOS and eNOS), and PKB phosphorylation in response to H-R (all
      P < 0.05 vs. H-R alone). These observations suggest that TGF-beta(1) decreases H
      R injury and attenuates alterations in NOS and PKB phosphorylation in myocytes
      exposed to H-R.

PMID- 11514270
TI  - Tyrosine phosphorylation following alterations in arteriolar intraluminal
      pressure and wall tension.
AB  - Arterioles respond to increased transmural pressure with myogenic constriction.
      The present study investigated the role of tyrosine phosphorylation in myogenic
      activity. Cannulated segments of a rat cremaster arteriole were fixed under
      pressure, followed by incubation with fluorescein isothiocyanate (FITC)
      conjugated anti-phosphotyrosine. Smooth muscle cell fluorescence intensity was
      measured with the use of confocal laser-scanning microscopy. Anti-phosphotyrosine
      fluorescence intensity in muscle cells of arterioles maintained at 100 mmHg was
      reduced by the tyrosine kinase inhibitor tyrphostin A47 (30 microM) and increased
      by the tyrosine phosphatase inhibitor pervanadate (100 microM). In time-course
      experiments, anti-phosphotyrosine fluorescence increased slowly (over 5 min)
      after an acute increase in intraluminal pressure, and was dissociated from
      myogenic contraction (within 1 min). In contrast, angiotensin II (0.1 microM)
      caused rapid constriction and increased tyrosine phosphorylation. Anti
      phosphotyrosine fluorescence was also pressure dependent (10-100 mmHg). Abolition
      of myogenic activity, either through removal of extracellular Ca2+, or exposure
      to verapamil (5 microM) or forskolin (0.1 microM) caused a further increase in
      anti-phosphotyrosine fluorescence. We conclude that transmural pressure and/or
      wall tension in arterioles causes increased tyrosine phosphorylation; however,
      this is not involved in the acute phase of myogenic constriction but may be
      involved in later responses, such as sustained myogenic tone or mechanisms
      possibly related to growth.

PMID- 11514271
TI  - K(V)alpha1 channels in murine arterioles: differential cellular expression and
      regulation of diameter.
AB  - The primary objectives of this study were to reveal cell-specific expression
      patterns and functions of voltage-gated K(+) channel (K(V)alpha1) subunits in
      precapillary arterioles of the murine cerebral circulation. K(V)alpha1 were
      detected using peptide-specific antibodies in immunofluorescence and Western
      blotting assays. K(V)1.2 was localized almost exclusively to endothelial cells,
      whereas K(V)1.5 was discretely localized to the nerves and nerve terminals that
      innervate the arterioles. K(V)1.5 also localized specifically to arteriolar
      nerves in human pial membrane. K(V)1.5 was notable for its absence from smooth
      muscle cells. K(V)1.3, K(V)1.4, and K(V)1.6 were localized to endothelial and
      smooth muscle cells, although K(V)1.4 had a low expression level. K(V)1.1 was not
      expressed. Therefore, we show that different cell types of pial arterioles have
      distinct physiological expression profiles of K(V)alpha1, conferring the
      possibility of differential modulation by extracellular and second messengers.
      Furthermore, we show recombinant agitoxin-2 and margatoxin are potent
      vasoconstrictors, suggesting that K(V)alpha1 subunits have a major function in
      determining arteriolar resistance to blood flow.

PMID- 11514272
TI  - Src tyrosine kinase is the trigger but not the mediator of ischemic
      preconditioning.
AB  - The signal cascade that triggers and mediates ischemic preconditioning (IPC)
      remains unclear. The present study investigated the role of the Src family of
      tyrosine kinases in IPC. Isolated and buffer-perfused rat hearts underwent IPC
      with three cycles of 5-min ischemia and 5-min reperfusion, followed by 30-min
      ischemia and 120-min reperfusion. The Src tyrosine kinase family-selective
      inhibitor PP1 was administered between 45 and 30 min before ischemia (early PP1
      treatment) or for 15 min before IPC [early PP1-preconditioning (PC) treatment].
      PP1 was also administered for 5 min before the sustained ischemia (late PP1
      treatment) or after IPC (late PP1-PC treatment). Src kinase was activated after
      30 min of ischemia in both the membrane and cytosolic fractions. Src kinase was
      also activated by IPC but was attenuated after the sustained ischemia. Early and
      late PP1 treatment inhibited Src activation after the sustained ischemia and
      reduced infarct size. Early PP1-PC inhibited Src activation after IPC but not
      after the sustained ischemia and blocked cardioprotection afforded by IPC. Late
      PP1-PC treatment abrogated IPC-induced activation of Src and protein kinase C
      (PKC)-epsilon in the membrane but not in the cytosolic fraction. This treatment
      modality abrogated Src activation after the sustained ischemia and failed to
      block cardioprotection afforded by IPC. These results suggest that Src kinase
      activation mediates ischemic injury but triggers IPC in the position either
      upstream of or parallel to membrane-associated PKC-epsilon.

PMID- 11514273
TI  - Hemorrhagic shock primes the hepatic portal circulation for the vasoconstrictive
      effects of endothelin-1.
AB  - To test whether hemorrhagic shock and resuscitation (HSR) alters the vascular
      responsiveness of the portohepatic circulation to endothelins (ETs), we studied
      the macro- and microcirculatory effects of the preferential ET(A) receptor
      agonist ET-1 and of the selective ET(B) receptor agonist sarafotoxin 6c (S6c)
      after 1 h of hemorrhagic hypotension and 5 h of volume resuscitation in the
      isolated perfused rat liver ex vivo using portal pressure-flow relationships and
      epifluorescence microscopy. Although HSR did not cause major disturbances of
      hepatic perfusion per se, the response to ET-1 (0.5 x 10(-9) M) was enhanced,
      leading to greater increases in portal driving pressure, total portal resistance,
      and zero-flow pressures and more pronounced decreases in portal flow, sinusoidal
      diameters, and hepatic oxygen delivery compared with time-matched sham shock
      controls. In sharp contrast, the constrictive response to S6c (0.25 x 10(-9) M)
      remained unchanged. Thus HSR primes the portohepatic circulation for the
      vasoconstrictive effects of ET-1 but does not alter the effects of the ET(B)
      receptor agonist S6c. The enhanced sinusoidal response may contribute to the
      subsequent development of hepatic microcirculatory failure after secondary
      insults that are associated with increased generation of ET-1.

PMID- 11514274
TI  - Relationship between interstitial fluid volume and pressure (compliance) in
      hypothyroid rats.
AB  - There is clinical and experimental evidence that lack of thyroid hormones may
      affect the composition and structure of the interstitium. This can influence the
      relationship between volume and pressure during changes in hydration.
      Hypothyrosis was induced in rats by thyroidectomy 8 wk before the experiments.
      Overhydration was induced by infusion of acetated Ringer, 5, 10, and 20% of the
      body weight, while fluid was withdrawn by peritoneal dialysis with hypertonic
      glucose. Interstitial fluid pressure (P(i)) in euvolemia (euvolemic control
      situation) and experimental situation was measured with micropipettes connected
      to a servocontrolled counterpressure system. The corresponding interstitial fluid
      volume (V(i)) was found as the difference between extracellular fluid volume
      measured as the distribution volume of (51)Cr-labeled EDTA and plasma volume
      measured using (125)I-labeled human serum albumin. In euvolemia, V(i) was similar
      or lower in the skin and higher in skeletal muscle of hypothyroid than in
      euthyroid control rats, whereas the corresponding P(i) was higher in all tissues.
      During overhydration, P(i) rose to the same absolute level in both types of rats,
      whereas during peritoneal dialysis there was a linear relationship between volume
      and pressure in all tissues and types of rats. Interstitial compliance (C(i)),
      calculated as the inverse value of the slope of the curve relating changes in
      volume and pressure in dehydration, did not differ significantly in the hindlimb
      skin of hypothyroid and euthyroid rats. However, in skeletal muscle, C(i) was 1.3
      and 2.0 ml. 100 g(-1). mmHg(-1) in hypothyroid and euthyroid rats (P < 0.01),
      with corresponding numbers for the back skin of 2.7 and 5.0 ml. 100 g(-1). mmHg(
      1) (P < 0.01). These experiments suggest that lack of thyroid hormones in rats
      changes the interstitial matrix, again leading to reduced C(i) and reduced
      ability to mobilize fluid from the interstitium.

PMID- 11514275
TI  - Time course of forearm arterial compliance changes during reactive hyperemia.
AB  - Ultrasonic studies have shown that arterial compliance increases after prolonged
      ischemia. The objective of the present study was to develop an alternative
      plethysmographic method to investigate compliance, exploring validity and
      clinical applicability. Forearm pulse volume (FPV) and blood pressure (BP) were
      used to establish the FPV-BP relationship. Forearm arterial compliance (FAC) was
      measured, and the area under the FAC-BP curve (FAC(AUC)) was determined. The time
      course curve of compliance changes during reactive hyperemia was obtained by
      continuous measurements of FAC(AUC) for 20 s before and for 300 s after arterial
      occlusion. This technique allows us to effectively assess compliance changes
      during reactive hyperemia. Furthermore, the selected measurement protocol
      indicated the necessity for continuous measurements to detect "true" maximal
      FAC(AUC) changes. On multivariate analysis, preischemic FAC(AUC) was mainly
      affected by sex, peak FAC(AUC) was affected by sex and systolic BP, percent
      changes were affected by plasma high-density and low-density lipoprotein
      cholesterol, peak time was affected by age and body mass index, and descent time
      was affected by plasma triglyceride levels. The proposed technique is highly
      sensitive and well comparable with the generally accepted echotracking system. It
      may thus be considered as an alternative tool to detect and monitor compliance
      changes induced by arterial occlusion.

PMID- 11514276
TI  - LV systolic performance improves with development of hypertrophy after transverse
      aortic constriction in mice.
AB  - Transverse aortic constriction (TAC) is an effective technique for inducing left
      ventricular (LV) hypertrophy in mice. With the use of transthoracic
      echocardiography and Doppler measurements, we studied the effects of an acute
      increase in pressure overload on LV contractile performance and peak systolic
      wall stress index (WSI) at early time points after TAC and the time course of the
      development of LV hypertrophy in mice. The LV mass index was similar between TAC
      and sham-operated mice at postoperative day 1 but progressively increased in TAC
      mice by day 10. There was no further increase in the LV mass index between
      postoperative days 10 and 20. On day 1, whereas peak systolic WSI increased
      significantly, the LV ejection fraction (LVEF) and percent fractional shortening
      (%FS) decreased in TAC mice compared with sham-operated mice. By day 10, peak
      systolic WSI, LVEF, and %FS had recovered to baseline levels and were not
      significantly different between postoperative days 10 and 20. Thus LV systolic
      performance in mice declines immediately after TAC, associated with increased
      peak systolic WSI, but recovers to baseline levels with the development of
      compensatory LV hypertrophy over 10-20 days.

PMID- 11514277
TI  - Effects of autonomic blockers on linear and nonlinear indexes of blood pressure
      and heart rate in SHR.
AB  - Recent results in normotensive Wistar-Kyoto (WKY) rats show that nonlinear method
      may be more specific to quantify sympathetic and parasympathetic activities than
      the low (LF) and high frequencies (HF) spectral powers of blood pressure (BP) and
      R-R interval (RR). The present study extends this conclusion to spontaneously
      hypertensive rats (SHR). Blood pressure was recorded for 30 min before and after
      intravenous injection of saline, hexamethonium, atropine, atenolol, or prazosin.
      Mean level, standard deviation (SD), spectral LF and HF components, and three
      nonlinear indexes (percentage of recurrence, percentage of determinism, and
      length index of the recurrence plot method) were used to analyze the BP and RR
      signals. In conscious SHR, sympathetic but not parasympathetic blockade reduced
      BP level and LF-BP, and increased nonlinear indexes of BP. RR increased after
      beta-sympathetic and ganglionic blockade, decreased after parasympathetic
      blockade, and remained unchanged after alpha(1)-sympathetic blockade. SD-RR
      decreased after ganglionic and alpha(1) blockade, whereas HF-RR increased after
      beta-sympathetic blockade. The effects on nonlinear indexes of RR are clear and
      consistent: only alpha(1)-blockade increased the indexes. Our nonlinear indexes
      may be useful to investigate cardiovascular functions in normotension and
      hypertension.

PMID- 11514278
TI  - Triglycerides impair postischemic recovery in isolated hearts: roles of
      endothelin-1 and trimetazidine.
AB  - There is growing evidence that hypertriglyceridemia exacerbates ischemic injury.
      We tested the hypothesis that triglycerides impair myocardial recovery from low
      flow ischemia in an ex vivo model and that such an effect is related to
      endothelin-1. Hyperglycemic (glucose concentration = 12 mmol/l) and
      hyperinsulinemic (insulin concentration = 1.2 micromol/l) isolated rat hearts
      were perfused with Krebs-Henseleit buffer (PO(2) = 670 mmHg, pH 7.4, 37 degrees
      C) added with increasing triglycerides (0, 1,000, 2,000, and 4,000 mg/dl, n = 6-9
      rats/group). Hearts were exposed to 60 min of low-flow ischemia (10% of basal
      coronary flow), followed by 30 min of reperfusion. We found that increasing
      triglycerides impaired both the diastolic (P < 0.005) and systolic (P < 0.02)
      recovery. The release of endothelin-1 during reperfusion increased linearly with
      triglyceride concentration (P = 0.0009). Elevated triglycerides also increased
      the release of nitrite and nitrate (NO(x)), the end products of nitric oxide, up
      to 6 micromol/min. Trimetazidine (1 micromol) further increased NO(x) release,
      blunted endothelin-1 release, and protected myocardial function during recovery.
      We conclude that high triglyceride levels impair myocardial recovery after low
      flow ischemia in association with endothelin-1 release. The endothelium-mediated
      effect of triglycerides on both contractile recovery and endothelin-1 release is
      prevented by 1 microM trimetazidine.

PMID- 11514279
TI  - Preserved contractile function despite atrophic remodeling in unloaded rat
      hearts.
AB  - The present study was designed to determine whether myocardial atrophy is
      necessarily associated with changes in cardiac contractility. Myocardial
      unloading of normal hearts was produced via heterotopic transplantation in rats.
      Contractions of isolated myocytes (1.2 mM Ca2+; 37 degrees C) were assessed
      during field stimulation (0.5, 1.0, and 2.0 Hz), and papillary muscle
      contractions were assessed during direct stimulation (2.0 mM Ca2+; 37 degrees C;
      0.5 Hz). Hemodynamic unloading was associated with a 41% decrease in median
      myocyte volume and proportional decreases in myocyte length and width.
      Nevertheless, atrophic myocytes had normal fractional shortening, time to peak
      contraction, and relaxation times. Despite decreases in absolute maximal force
      generation (F(max)), there were no differences in F(max)/ area in papillary
      muscles isolated from unloaded transplanted hearts. Therefore, atrophic
      remodeling after unloading is associated with intact contractile function in
      isolated myocytes and papillary muscles when contractile indexes are normalized
      to account for reductions in cell length and cross-sectional area, respectively.
      Nevertheless, in the absence of compensatory increases in contractile function,
      reductions in myocardial mass will lead to impaired overall work capacity.

PMID- 11514280
TI  - Altered SR protein expression associated with contractile dysfunction in diabetic
      rat hearts.
AB  - The goal of this study was to examine whether alteration of sarcoplasmic
      reticulum (SR) protein levels is associated with early-onset diastolic and late
      onset systolic dysfunction in streptozotocin (STZ)-induced diabetic rat hearts.
      Four-week diabetic rat hearts exhibited slow relaxation, whereas 6-wk diabetic
      rat hearts exhibited slow and depressed contraction. Total phospholamban level
      was increased, and phosphorylated level was decreased in 4- and 6-wk diabetic rat
      hearts. Sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA2) protein level was
      unchanged in 4-wk but decreased in 6-wk diabetic rat hearts. Only the apparent
      affinity of SR Ca2+ uptake for Ca2+ was decreased in 4-wk diabetic rat hearts,
      but the apparent affinity and the maximum rate was decreased in 6-wk diabetic rat
      hearts. Insulin treatment of the diabetic rats normalized SR protein expression
      and function. It was concluded that an increase in nonphosphorylated
      phospholamban and a decrease in the apparent affinity of SR Ca2+ pump for Ca2+
      are associated with early-onset diastolic dysfunction and decreases in SERCA2
      protein level and apparent affinity and maximum velocity of SR Ca2+ pump are
      associated with late-onset systolic dysfunction in diabetic rats.

PMID- 11514281
TI  - Beat-to-beat stroke volume estimation from aortic pressure waveform in conscious
      rats: comparison of models.
AB  - Several methods for estimating stroke volume (SV) were tested in conscious,
      freely moving rats in which ascending aortic pressure and cardiac flow were
      simultaneously (beat-to-beat) recorded. We compared two pulse-contour models to
      two new statistical models including eight parameters extracted from the pressure
      waveform in a multiple linear regression. Global as well as individual
      statistical models gave higher correlation coefficients between estimated and
      measured SV (model 1, r = 0.97; model 2, r = 0.96) than pulse-contour models
      (model 1, r = 0.83; model 2, r = 0.91). The latter models as well as statistical
      model 1 used the pulsatile systolic area and thus could be applied to only 47 +/-
      17% of the cardiac beats. In contrast, statistical model 2 used the pressure
      increase characteristics and was therefore established for all of the cardiac
      beats. The global statistical model 2 applied to data sets independent of those
      used to establish the model gave reliable SV estimates: r = 0.54 +/- 0.07, a
      small bias between -8% to +10%, and a mean precision of 7%. This work
      demonstrated the limits of pulse-contour models to estimate SV in conscious,
      unrestrained rats. A multivariate statistical model using eight parameters easily
      extracted from the aortic waveform could be applied to all cardiac beats with
      good precision.

PMID- 11514282
TI  - Role of smooth muscle cells on endothelial cell cytosolic free calcium in porcine
      coronary arteries.
AB  - We tested the hypothesis that the cytosolic free calcium concentration in
      endothelial cells is under the influence of the smooth muscle cells in the
      coronary circulation. In the left descending branch of porcine coronary arteries,
      cytosolic free calcium concentration ([Ca(2+)](i)) was estimated by determining
      the fluorescence ratio of two calcium probes, fluo 4 and fura red, in smooth
      muscle and endothelial cells using confocal microscopy. Acetylcholine and
      potassium, which act directly on smooth muscle cells to increase [Ca(2+)](i),
      were found to indirectly elevate [Ca(2+)](i) in endothelial cells; in primary
      cultures of endothelial cells, neither stimulus affected [Ca(2+)](i), yet
      substance P increased the fluorescence ratio twofold. In response to
      acetylcholine and potassium, isometric tension developed by arterial strips with
      intact endothelium was attenuated by up to 22% (P < 0.05) compared with strips
      without endothelium. These findings suggest that stimuli that increase smooth
      muscle [Ca(2+)](i) can indirectly influence endothelial cell function in porcine
      coronary arteries. Such a pathway for negative feedback can moderate
      vasoconstriction and diminish the potential for vasospasm in the coronary
      circulation.

PMID- 11514283
TI  - Angiotensin II and VEGF are involved in angiogenesis induced by short-term
      exercise training.
AB  - Results from our laboratory have suggested a pathway involving angiotensin II
      type 1 (AT(1)) receptors and vascular endothelial growth factor (VEGF) in
      angiogenesis induced by electrical stimulation. The present study investigated if
      similar mechanisms underlie the angiogenesis induced by short-term exercise
      training. Seven days before training and throughout the training period, male
      Sprague-Dawley rats received either captopril or losartan in their drinking
      water. Rats underwent a 3-day treadmill training protocol. The tibialis anterior
      and gastrocnemius muscles were harvested under anesthesia and lightly fixed in
      formalin (vessel density) or frozen in liquid nitrogen (VEGF expression). In
      controls, treadmill training resulted in a significant increase in vessel density
      in all muscles studied. However, the angiogenesis induced by exercise was
      completely blocked by either losartan or captopril. Western blot analysis showed
      that VEGF expression was increased in the exercised control group, and both
      losartan and captopril blocked this increase. The role of VEGF was directly
      confirmed using a VEGF-neutralizing antibody. These results confirm the role of
      angiotensin II and VEGF in angiogenesis induced by exercise.

PMID- 11514284
TI  - Hindlimb unweighting affects rat vascular capacitance function.
AB  - Microgravity is associated with an impaired stroke volume and, therefore, cardiac
      output response to orthostatic stress. We hypothesized that a decreased venous
      filling pressure due to increased venous compliance may be an important
      contributing factor in this response. We used a constant flow, constant right
      atrial pressure cardiopulmonary bypass procedure to measure total systemic
      vascular compliance (C(T)), arterial compliance (C(A)), and venous compliance
      (C(V)) in seven control and seven 21-day hindlimb unweighted (HLU) rats. These
      compliance values were calculated under baseline conditions and during an
      infusion of 0.2 microg*kg(-1)*min(-1) norepinephrine (NE). The change in
      reservoir volume, which reflects changes in unstressed vascular volume
      (DeltaV(0)) that occurred upon infusion of NE, was also measured. C(T) and C(V)
      were larger in HLU rats both at baseline and during the NE infusion (P < 0.05).
      Infusion of NE decreased C(T) and C(V) by ~20% in both HLU and control rats (P <
      0.01). C(A) was also significantly decreased in both groups of rats by NE (P <
      0.01), but values of C(A) were similar between HLU and control rats both at
      baseline and during the NE infusion. Additionally, the NE-induced DeltaV(0) was
      attenuated by 53% in HLU rats compared with control rats (P < 0.05). The larger
      C(V) and attenuated DeltaV(0) in HLU rats could contribute to a decreased filling
      pressure during orthostasis and thus may partially underlie the mechanism leading
      to the exaggerated fall in stroke volume and cardiac output seen in astronauts
      during an orthostatic stress after exposure to microgravity.

PMID- 11514285
TI  - AM reverses pressor response to ET-1 independently of NO in rat coronary
      circulation.
AB  - Endothelin-1 (ET-1) elicits a vasoconstrictor response via ET(A) receptors,
      whereas simultaneous activation of ET(B) receptors triggers the release of nitric
      oxide (NO), which may limit the constrictor effect of ET-1. Recently, stimulation
      of ET(B) receptors has been shown to increase the secretion of adrenomedullin
      (AM), a newly identified vasorelaxing peptide. The present study was designed to
      see whether AM can oppose the vasoconstrictor response to ET-1. In the isolated
      perfused paced rat heart preparation, infusion of ET-1 at concentrations of 1
      nmol/l for 30 min induced a significant coronary vasoconstriction, whereas it had
      no effect on perfusion pressure at a dose of 0.08 nmol/l. N(omega)-nitro-L
      arginine methyl ester (L-NAME; 300 micromol/l), a potent inhibitor of NO synthase
      (NOS), did not change the perfusion pressure when added alone to the perfusion
      fluid but it unmasked the constrictor effect of ET-1 at both concentrations. In
      the presence of L-NAME, AM (0.03 to 1 nmol/l) markedly reversed the pressor
      response to ET-1 at both concentrations. Administration of AM (0.03 and 1 nmol/l)
      alone resulted in a dose-dependent decrease in perfusion pressure, which was not
      modified in the presence of L-NAME. In conclusion, the coronary vasoconstrictor
      response to ET-1 is markedly augmented in the presence of a NOS inhibitor. This
      constrictor response is substantially reversed by AM. Our results indicate that
      AM may serve as a paracrine modulator of ET-1-induced vasoconstriction
      independently of the NO pathway.

PMID- 11514286
TI  - Stress-activated protein kinase phosphorylation during cardioprotection in the
      ischemic myocardium.
AB  - Stress-activated protein kinases may be essential to cardioprotection. We
      assessed the role of p38 in an in vivo rat model of ischemia-reperfusion.
      Ischemic preconditioning (IPC) and the delta(1)-opioid receptor agonist 2-methyl
      4aalpha-(3-hydroxyphenyl)-1,2,3,4,4a,5,12,12aalpha-octahydroquinolino [2,3,3
      g]isoquinoline (TAN-67) significantly reduced infarct size (IS), expressed as a
      percentage of the area at risk (AAR), versus animals subjected only to 30 min of
      ischemia and 2 h of reperfusion (7.1 +/- 1.5 and 29.6 +/- 3.3 vs. 59.7 +/- 1.6%).
      The p38 antagonist SB-203580 attenuated IPC when it was administered before (34.0
      +/- 6.9%) or after (25.0 +/- 3.8%) the IPC stimulus; however, it did not
      significantly attenuate TAN-67-induced cardioprotection (39.6 +/- 3.2). We also
      assessed the phosphorylation of p38 and c-jun NH(2)-terminal kinase (JNK)
      throughout ischemia-reperfusion in nuclear and cytosolic fractions. After either
      intervention, no increase was detected in the phosphorylation state of either
      enzyme in the nuclear fraction or for p38 in the cytosolic fraction versus
      control hearts. However, there was a robust increase in JNK activity in the
      cytosolic fraction immediately on reperfusion that was more pronounced in animals
      subjected to IPC or administered TAN-67. These data suggest that SB-203580 likely
      attenuates IPC via the inhibition of kinases other than p38, which may include
      JNK. The data also suggest that activation of JNK during early reperfusion may be
      an important component of cardioprotection.

PMID- 11514287
TI  - Adenosine linking reduced O2 to arteriolar NO release in intestine is not formed
      from extracellular ATP.
AB  - We have previously reported that adenosine formed in response to reduced
      arteriolar and/or tissue PO(2) preserves endothelial nitric oxide (NO) synthesis
      during sympathetic vasoconstriction in the rat intestine. To more precisely
      identify the site and mechanism of adenosine formation under these conditions, we
      tested the hypothesis that ATP released in response to reduced O(2) levels serves
      as a source of adenosine. Direct application of ATP to the wall of first-order
      arterioles elicited dose-dependent dilations of 15-33% above resting diameter
      that were reduced by 71-80% by the 5'-ectonucleotidase inhibitor alpha,beta
      methyleneadenosine 5'-diphosphate (AOPCP, 4.5 x 10(-5) M) and completely
      abolished by N(G)-monomethyl-L-arginine (L-NMMA, 10(-4) M). Under control
      conditions, sympathetic nerve stimulation at 3 and 8 Hz induced arteriolar
      constrictions of 11 +/- 1 and 19 +/- 1 microm, respectively. These responses were
      enhanced by 58-69% in the presence of L-NMMA or when local PO(2) was maintained
      at resting levels. However, in the presence of AOPCP, the enhancing effects of L
      NMMA and the high O(2) superfusate on sympathetic constriction were preserved.
      These results suggest that, although exogenously applied ATP can stimulate
      arteriolar NO release in the intestine largely through its sequential
      extracellular hydrolysis to adenosine, this process does not contribute to
      adenosine formation and sustained NO release during sympathetic constriction in
      this vascular bed.

PMID- 11514288
TI  - Characterization of mice with a combined suppression of I(to) and I(K,slow).
AB  - Cardiac-specific expression of a truncated Kv1.1 polypeptide (Kv1DN) attenuates
      the slow inactivating outward K(+) current (I(K,slow)), increases action
      potential duration (APD) and Q-T intervals, and induces spontaneous ventricular
      arrhythmias. Expression of the pore mutant of Kv4.2 (Kv4DN) eliminates the fast
      component of the transient outward current (I(to)) and prolongs APDs and Q-T
      intervals markedly; however, no arrhythmias are seen in Kv4DN mice, suggesting
      that APD and Q-T prolongation are not per se proarrhythmic. To test this
      hypothesis, the Kv1DN and Kv4DN lines were crossbred to produce animals
      (Kv1/Kv4DN) expressing both transgenes in an identical genetic background. Whole
      cell voltage-clamp recordings from left ventricular apex cells confirmed that in
      Kv1/Kv4DN left ventricular apex cells, both components (fast and slow) of I(to)
      and the 4-aminopyridine-sensitive component of I(K,slow) are eliminated,
      resulting in marked APD prolongation compared with wild-type, Kv1DN, or Kv4DN
      cells. Telemetric electrocardiogram monitoring (n = 10 mice/group) revealed a
      significant prolongation of Q-Tc and P-R intervals in Kv1/Kv4DN animals compared
      with Kv1DN or Kv4DN animals. Spontaneous arrhythmias were observed mainly in
      Kv1DN mice. Thus the attenuation of fast I(to) in addition to I(K,slow) in
      Kv1/Kv4DN mice causes significant prolongation of APD and Q-T intervals and
      attenuation of spontaneous arrhythmias.

PMID- 11514289
TI  - ANG II in median preoptic nucleus and pressor responses to CSF sodium and high
      sodium intake in SHR.
AB  - Pressor responses to increases in cerebrospinal fluid (CSF) sodium in Wistar rats
      and to high salt intake in spontaneously hypertensive rats (SHR) involve both
      brain ouabainlike activity ("ouabain") and the brain renin-angiotensin system
      (RAS). Because some of the effects of "ouabain" are mediated by the median
      preoptic nucleus (MnPO) and this nucleus contains all elements of the RAS, the
      present study assessed possible interactions of "ouabain" and ANG II in this
      nucleus. In conscious Wistar rats, injection of ANG II into the MnPO
      significantly increased mean arterial pressure (MAP) and heart rate (HR). This
      response was not affected by pretreatment with a subpressor dose of ouabain. MAP
      and HR increases by ouabain in the MnPO were significantly attenuated by MnPO
      pretreatment with losartan. In Wistar rats, losartan in the MnPO also abolished
      pressor and HR responses to intracerebroventricular 0.3 M NaCl and attenuated MAP
      and HR responses to intracerebroventricular ouabain. Five weeks of a high-salt
      diet in SHRs resulted in exacerbation of hypertension and increased responses to
      air-jet stress and intracerebroventricular guanabenz. Losartan injected into the
      MnPO reversed the salt-sensitive component of the hypertension and normalized the
      depressor response to guanabenz but did not change responses to air-jet stress.
      We conclude that in the MnPO, ANG II via AT(1) receptors mediates cardiovascular
      responses to an acute increase in CSF sodium as well as the chronic pressor
      responses to high sodium intake in SHR.

PMID- 11514290
TI  - Loaded shortening and power output in cardiac myocytes are dependent on myosin
      heavy chain isoform expression.
AB  - The purpose of this study was to examine the role of myosin heavy chain (MHC) in
      determining loaded shortening velocities and power output in cardiac myocytes.
      Cardiac myocytes were obtained from euthyroid rats that expressed alpha-MHC or
      from thyroidectomized rats that expressed beta-MHC. Skinned myocytes were
      attached to a force transducer and a position motor, and isotonic shortening
      velocities were measured at several loads during steady-state maximal Ca(2+)
      activation (P(pCa4.5)). MHC expression was determined after mechanical
      measurements using SDS-PAGE. Both alpha-MHC and beta-MHC myocytes generated
      similar maximal Ca(2+)-activated force, but alpha-MHC myocytes shortened faster
      at all loads and generated approximately 170% greater peak normalized power
      output. Additionally, the curvature of force-velocity relationships was less, and
      therefore the relative load optimal for power output (F(opt)) was greater in
      alpha-MHC myocytes. F(opt) was 0.31 +/- 0.03 P(pCa4.5) and 0.20 +/- 0.06
      P(pCa4.5) for alpha-MHC and beta-MHC myocytes, respectively. These results
      indicate that MHC expression is a primary determinant of the shape of force
      velocity relationships, velocity of loaded shortening, and overall power output
      generating capacity of individual cardiac myocytes.

PMID- 11514291
TI  - Effects of dietary phytoestrogen on global myocardial ischemia-reperfusion injury
      in isolated female rat hearts.
AB  - We investigated the effects of phytoestrogen on global myocardial ischemia
      reperfusion injury in five groups of female rats. A high-phytoestrogen group
      (HPE) was ovariectomized (Ovx) and fed a diet containing soybean protein and a
      high-isoflavone soy extract. Another Ovx group of rats was fed the same diet as
      the HPE group but treated with the estrogen receptor blocker ICI-182,780 (HPE +
      ICI). A third group of Ovx rats was fed a diet containing soybean protein alone
      (low-phytoestrogen content; LPE). A fourth Ovx group was fed a diet free of
      phytoestrogen (Ovx). The fifth group of rats was sham ovariectomized (sham).
      Hearts from all rats were subjected to 30 min of global, hypothermic (4 degrees
      C), cardioplegic ischemia and 120 min of normothermic (37 degrees C) reperfusion
      with oxygenated Krebs-Henseleit buffer. Compared with either the sham or the HPE
      group, the Ovx and HPE + ICI groups had significantly decreased first derivative
      of left ventricular pressure (dP/dt), coronary flow rate (CFR), nitrite
      production and mitochondrial respiratory function and significantly increased
      Ca2+ accumulation and myocardial histological and ultrastructural injury. The CFR
      of the LPE group was significantly different from that of either Ovx or HPE + ICI
      group but the dP/dt, nitrite production, Ca2+ accumulation, and mitochondrial
      function were not. Our results indicate that diets containing phytoestrogen
      extract play a cardioprotective role in global myocardial ischemia-reperfusion in
      female rats.

PMID- 11514292
TI  - Paraventricular nucleus bicuculline alters frequency components of sympathetic
      nerve discharge bursts.
AB  - Autospectral and coherence analyses were used to determine the effect of
      paraventricular nucleus (PVN) GABA(A) receptor antagonism [microinfusion or
      microinjections of bicuculline methiodide (BMI) 100 pmoles] on sympathetic nerve
      discharge (SND) frequency components (bursting pattern and relationships between
      discharges in regionally selective nerves) in alpha-chloralose-anesthetized rats.
      SND was recorded from the renal, splenic, and lumbar nerves. The following
      observations were made. First, PVN BMI microinjections, but not PVN saline or
      cortical BMI microinjections, transformed the cardiac-related SND bursting
      pattern in baroreceptor-innervated rats to one characterized by the presence of
      low-frequency bursts not synchronized to the cardiac cycle or phrenic nerve
      discharge bursts. Second, SND pattern changes were similar in the renal, splenic,
      and lumbar nerves, and peak coherence values relating low-frequency bursts in
      sympathetic nerve pairs (renal-splenic, renal-lumbar, and splenic-lumbar) were
      significantly increased from preinjection control after PVN BMI microinjection.
      Third, PVN BMI microinjections significantly increased the coupling between low
      frequency SND bursts in baroreceptor-denervated rats. Finally, PVN BMI-induced
      changes in the SND bursting pattern were not observed after PVN pretreatment with
      muscimol (GABA agonist, 1 nmole). We conclude that PVN GABA(A) receptor
      antagonism profoundly alters the frequency components in sympathetic nerves.

PMID- 11514293
TI  - Effects of chronic alcohol consumption on regulation of myocardial protein
      synthesis.
AB  - Heart disease represents an important etiology of mortality in chronic
      alcoholics. The purpose of the present study was to examine potential mechanisms
      for the inhibitory effect of chronic alcohol exposure (16 wk) on the regulation
      of myocardial protein metabolism. Chronic alcohol feeding resulted in a lower
      heart weight and 25% loss of cardiac protein per heart compared with pair-fed
      controls. The loss of protein mass resulted in part from a diminished (30%) rate
      of protein synthesis. Ethanol exerted its inhibition of protein synthesis through
      diminished translational efficiency rather than lower RNA content. Chronic
      ethanol administration decreased the abundance of eukaryotic initiation factor
      (eIF)4G associated with eIF4E in the myocardium by 36% and increased the
      abundance of the translation response protein (4E-BP1) associated with eIF4E. In
      addition, chronic alcohol feeding significantly reduced the extent of p70S6
      kinase (p70(S6K)) phosphorylation. The decreases in the phosphorylation of 4E-BP1
      and p70(S6K) did not result from a reduced abundance of mammalian target of
      rapamycin (mTOR). These data suggest that a chronic alcohol-induced impairment in
      myocardial protein synthesis results in part from inhibition in peptide chain
      initiation secondary to marked changes in eIF4E availability and p70(S6K)
      phosphorylation.

PMID- 11514294
TI  - L-type but not T-type calcium current changes during postnatal development in
      rabbit sinoatrial node.
AB  - Although the neonatal sinus node beats at a faster rate than the adult, when a
      sodium current (I(Na)) present in the newborn is blocked, the spontaneous rate is
      slower in neonatal myocytes than in adult myocytes. This suggests a possible
      functional substitution of I(Na) by another current during development. We used
      ruptured [T-type calcium current (I(Ca,T))] and perforated [L-type calcium
      current (I(Ca,L))] patch clamps to study developmental changes in calcium
      currents in sinus node cells from adult and newborn rabbits. I(Ca,T) density did
      not differ with age, and no significant differences were found in the voltage
      dependence of activation or inactivation. I(Ca,L) density was lower in the adult
      than newborn (12.1 +/- 1.4 vs. 17.6 +/- 2.5 pA/pF, P = 0.049). However,
      activation and inactivation midpoints were shifted in opposite directions,
      reducing the potential contribution during late diastolic depolarization in the
      newborn (activation midpoints -17.3 +/- 0.8 and -22.3 +/- 1.4 mV in the newborn
      and adult, respectively, P = 0.001; inactivation midpoints -33.4 +/- 1.4 and 
      28.3 +/- 1.7 mV for the newborn and adult, respectively, P = 0.038). Recovery of
      I(Ca,L) from inactivation was also slower in the newborn. The results suggest
      that a smaller but more negatively activating and rapidly recovering I(Ca,L) in
      the adult sinus node may contribute to the enhanced impulse initiation at this
      age in the absence of I(Na).

PMID- 11514295
TI  - Na(+)/H(+) exchange inhibition prevents endothelial dysfunction after I/R injury.
AB  - Whereas inhibition of the Na(+)/H(+) exchanger (NHE) has been demonstrated to
      reduce myocardial infarct size in response to ischemia-reperfusion injury, the
      ability of NHE inhibition to preserve endothelial cell function has not been
      examined. This study examined whether NHE inhibition could preserve endothelial
      cell function after 90 min of regional ischemia and 180 min of reperfusion and
      compared this inhibition with ischemic preconditioning (IPC). In a canine model
      either IPC, produced by one 5-min coronary artery occlusion (1 x 5'), or the
      specific NHE-1 inhibitor eniporide (EMD-96785, 3.0 mg/kg) was administered 15 min
      before a 90-min coronary artery occlusion followed by 3 h of reperfusion. Infarct
      size (IS) was determined by 2,3,5-triphenyl tetrazolium chloride staining and
      expressed as a percentage of the area-at-risk (IS/AAR). Endothelial cell function
      was assessed by measurement of coronary blood flow in response to intracoronary
      acetylcholine infusion at the end of reperfusion. Whereas neither control nor IPC
      treated animals exhibited a significant reduction in IS/AAR or preservation of
      endothelial cell function, animals treated with the NHE inhibitor eniporide
      showed a marked reduction in IS/AAR and a significantly preserved endothelial
      cell function (P < 0.05). Thus NHE-1 inhibition is more efficacious than IPC at
      reducing IS/AAR and at preserving endothelial cell function in dogs.

PMID- 11514296
TI  - Smaller age-associated reductions in leg venous compliance in endurance exercise
      trained men.
AB  - We determined the independent and interactive influences of aging and habitual
      endurance exercise on calf venous compliance in humans. We tested the hypotheses
      that calf venous compliance is 1) reduced with age in sedentary and endurance
      trained men, and 2) elevated in young and older endurance-trained compared with
      age-matched sedentary men. We studied 8 young (28 +/- 1 yr) and 8 older (65 +/-
      1) sedentary, and 8 young (27 +/- 1) and 8 older (63 +/- 2) endurance-trained
      men. Calf venous compliance was measured in supine subjects by inflating a venous
      collecting cuff, placed above the knee, to 60 mmHg for 8 min and then decreasing
      cuff pressure at 1 mmHg/s to 0 mmHg. Calf venous compliance was determined using
      the first derivative of the pressure-volume relation during cuff pressure
      reduction (compliance = beta(1) + 2. beta(2). cuff pressure). Calf venous
      compliance was reduced with age in sedentary (approximately 40%) and endurance
      trained men (approximately 20%) (both P < 0.01). Furthermore, calf venous
      compliance was approximately 70-120% greater in endurance-trained compared with
      age-matched sedentary men and approximately 30% greater in older endurance
      trained compared with young sedentary men (both P < 0.01). These data indicate
      that calf venous compliance is reduced with age in sedentary and endurance
      trained men, but compliance is better preserved in endurance-trained men.

PMID- 11514297
TI  - Central volume expansion is pivotal for sustained decrease in heart rate during
      seated to supine posture change.
AB  - During prolonged, static carotid baroreceptor stimulation by neck suction (NS) in
      seated humans, heart rate (HR) decreases acutely and thereafter gradually
      increases. This increase has been explained by carotid baroreceptor adaptation
      and/or buffering by aortic reflexes. During a posture change from seated to
      supine (Sup) with similar carotid stimulation, however, the decrease in HR is
      sustained. To investigate whether this discrepancy is caused by changes in
      central blood volume, we compared (n = 10 subjects) the effects of 10 min of
      seated NS (adjusted to simulate carotid stimulation of a posture change), a
      posture change from seated to Sup, and the same posture change with left atrial
      (LA) diameter maintained unchanged by lower body negative pressure (Sup + LBNP).
      During Sup, the prompt decreases in HR and mean arterial pressure (MAP) were
      sustained. HR decreased similarly within 30 s of NS (65 +/- 2 to 59 +/- 2
      beats/min) and Sup + LBNP (65 +/- 2 to 58 +/- 2 beats/min) and thereafter
      gradually increased to values of seated. MAP decreased similarly within 5 min
      during Sup + LBNP and NS (by 7 +/- 1 to 9 +/- 1 mmHg) and thereafter tended to
      increase toward values of seated subjects. Arterial pulse pressure was increased
      the most by Sup, less so by Sup + LBNP, and was unchanged by NS. LA diameter was
      only increased by Sup. In conclusion, static carotid baroreceptor stimulation per
      se causes the acute (<30 s) decrease in HR during a posture change from seated to
      Sup, whereas the central volume expansion (increased LA diameter and/or arterial
      pulse pressure) is pivotal to sustain this decrease. Thus the effects of central
      volume expansion override adaptation of the carotid baroreceptors and/or
      buffering of aortic reflexes.

PMID- 11514298
TI  - MR imaging measurement of compartmental water diffusion in perfused heart slices.
AB  - Myocardial tissue slices were isolated from the left ventricular free wall (7
      slices) and left ventricular papillary muscle (3 slices) of New Zealand White
      male rabbits (n = 4) and were subsequently superfused with a modified St. Thomas'
      Hospital cardioplegic solution at 19 degrees C. The diffusion-weighted images
      were obtained with a 600-MHz nuclear magnetic resonance spectrometer using
      diffusion gradient b-values that ranged from 166 to 6,408 s/mm(2); the apparent
      diffusion coefficient of water in the tissues were subsequently calculated. All
      of the tissue samples that were studied exhibited nonmonoexponential diffusion.
      Data from seven slices were mathematically fitted by a biexponential expression
      with a fast diffusion component of 0.72 +/- 0.07 x 10(-3) mm(2)/s, and a slow
      diffusion component of 0.060 +/- 0.033 x 10(-3) mm(2)/s. The fast component
      dominated the calculated apparent diffusion coefficient of the tissue, composed
      of 82 +/- 3% of the overall diffusion-dependent signal decay. Thus myocardial
      tissue exhibits characteristics consistent with multiple compartments of
      diffusion. This work has important implications for myocardial diffusion tensor
      imaging, as well as the changes in diffusion that have been reported following
      myocardial ischemia.

PMID- 11514299
TI  - Rat cardiac contractile dysfunction induced by Ca2+ overload: possible link to
      the proteolysis of alpha-fodrin.
AB  - The aim of the present study was to examine the mechanisms of Ca2+ overload
      induced contractile dysfunction in rat hearts independent of ischemia and
      acidosis. Experiments were performed on 30 excised cross-circulated rat heart
      preparations. After hearts were exposed to high Ca2+, there was a contractile
      failure associated with a parallel downward shift of the linear relation between
      myocardial O(2) consumption per beat and systolic pressure-volume area (index of
      a total mechanical energy per beat) in left ventricles from all seven hearts that
      underwent the protocol. This result suggested a decrease in O(2) consumption for
      total Ca2+ handling in excitation-contraction coupling. In the hearts that
      underwent the high Ca2+ protocol and had contractile failure, we found marked
      proteolysis of a cytoskeleton protein, alpha-fodrin, whereas other proteins were
      unaffected. A calpain inhibitor suppressed the contractile failure by high Ca2+,
      the decrease in O(2) consumption for total Ca2+ handling, and membrane alpha
      fodrin degradation. We conclude that the exposure to high Ca2+ may induce
      contractile dysfunction possibly by suppressing total Ca2+ handling in excitation
      contraction coupling and degradation of membrane alpha-fodrin via activation of
      calpain.

PMID- 11514300
TI  - Mitochondrial K(ATP) channel activation reduces anoxic injury by restoring
      mitochondrial membrane potential.
AB  - Mitochondrial membrane potential (DeltaPsi(m)) is severely compromised in the
      myocardium after ischemia-reperfusion and triggers apoptotic events leading to
      cell demise. This study tests the hypothesis that mitochondrial ATP-sensitive
      K(+) (mitoK(ATP)) channel activation prevents the collapse of DeltaPsi(m) in
      myocytes during anoxia-reoxygenation (A-R) and is responsible for cell protection
      via inhibition of apoptosis. After 3-h anoxia and 2-h reoxygenation, the cultured
      myocytes underwent extensive damage, as evidenced by decreased cell viability,
      compromised membrane permeability, increased apoptosis, and decreased ATP
      concentration. Mitochondria in A-R myocytes were swollen and fuzzy as shown after
      staining with Mito Tracker Orange CMTMRos and in an electron microscope and
      exhibited a collapsed DeltaPsi(m), as monitored by 5,5',6,6'-tetrachloro
      1,1',3,3'-tetraethylbenzimidazolcarbocyanine iodide (JC-1). Cytochrome c was
      released from mitochondria into the cytosol as demonstrated by cytochrome c
      immunostaining. Activation of mitoK(ATP) channel with diazoxide (100 micromol/l)
      resulted in a significant protection against mitochondrial damage, ATP depletion,
      cytochrome c loss, and stabilized DeltaPsi(m). This protection was blocked by 5
      hydroxydecanoate (500 micromol/l), a mitoK(ATP) channel-selective inhibitor, but
      not by HMR-1098 (30 micromol/l), a putative sarcolemmal K(ATP) channel-selective
      inhibitor. Dissipation of DeltaPsi(m) also leads to opening of mitochondrial
      permeability transition pore, which was prevented by cyclosporin A. The data
      support the hypothesis that A-R disrupts DeltaPsi(m) and induces apoptosis, which
      are prevented by the activation of the mitoK(ATP) channel. This further
      emphasizes the therapeutic significance of mitoK(ATP) channel agonists in the
      prevention of ischemia-reperfusion cell injury.

PMID- 11514302
TI  - Effect of adenosine receptor blockade with caffeine on sympathetic response to
      handgrip exercise in heart failure.
AB  - Adenosine (Ado) increases muscle sympathetic nerve activity (MSNA) reflexively.
      Plasma Ado and MSNA are elevated in heart failure (HF). We tested the hypothesis
      that Ado receptor blockade by caffeine would attenuate reflex MSNA responses to
      handgrip (HG) and posthandgrip ischemia (PHGI) and that this action would be more
      prominent in HF subjects than in normal subjects. We studied 12 HF subjects and
      10 age-matched normal subjects after either saline or caffeine (4 mg/kg) infusion
      during isometric [30% of maximal voluntary contraction (MVC)] and isotonic (10%,
      30%, and 50%) HG exercise, followed by 2 min of PHGI. In normal subjects,
      caffeine did not block increases in MSNA during PHGI after 50% HG. In HF
      subjects, caffeine abolished MSNA responses to PHGI after both isometric and 50%
      isotonic exercise (P < 0.05) but MSNA responses during HG were unaffected. These
      findings are consistent with muscle metaboreflex stimulation by endogenous Ado
      during ischemic or intense nonischemic HG in HF and suggest an important
      sympathoexcitatory role for endogenous Ado during exercise in this condition.

PMID- 11514301
TI  - Impaired NO-dependent dilation of skeletal muscle arterioles in hypertensive
      diabetic obese Zucker rats.
AB  - This study determined alterations to nitric oxide (NO)-dependent dilation of
      skeletal muscle arterioles from obese (OZR) versus lean Zucker rats (LZR). In
      situ cremaster muscle arterioles from both groups were viewed via television
      microscopy, and vessel dilation was measured with a video micrometer. Arteriolar
      dilation to acetylcholine and sodium nitroprusside was reduced in OZR versus LZR,
      although dilation to aprikalim was unaltered. NO-dependent flow-induced
      arteriolar dilation (via parallel microvessel occlusion) was attenuated in OZR,
      impairing arteriolar ability to regulate wall shear rate. Vascular superoxide
      levels, as assessed by dihydroethidine fluorescence, were elevated in OZR versus
      LZR. Treatment of cremaster muscles of OZR with the superoxide scavengers
      polyethylene glycol-superoxide dismutase and catalase improved arteriolar
      dilation to acetylcholine and sodium nitroprusside and restored flow-induced
      dilation and microvascular ability to regulate wall shear rate. These results
      suggest that NO-dependent dilation of skeletal muscle microvessels in OZR is
      impaired due to increased levels of superoxide. Taken together, these data
      suggest that the development of diabetes and hypertension in OZR may be
      associated with an impaired skeletal muscle perfusion via an elevated vascular
      oxidant stress.

PMID- 11514303
TI  - Mitochondrial ATPase and high-energy phosphates in failing hearts.
AB  - This study examined high-energy phosphates (HEP) and mitochondrial ATPase protein
      expression in hearts in which myocardial infarction resulted in either
      compensated left ventricular remodeling (LVR) or congestive heart failure (CHF).
      The response of HEP (measured via (31)P magnetic resonance spectroscopy) to a
      modest increase in the cardiac work state produced by dobutamine-dopamine
      infusion and pacing (if needed) was examined in 17 pigs after left circumflex
      coronary artery ligation (9 with LVR and 8 with CHF) and compared with 7 normal
      pigs. In hearts with LVR, the baseline phosphocreatine (PCr)-to-ATP ratio
      decreased, and calculated ADP increased; these changes were most severe in hearts
      with CHF. HEP levels did not change in normal or LVR hearts during dobutamine
      dopamine infusion. However, in hearts with CHF, the PCr-to-ATP ratio decreased
      further, and free ADP increased. The mitochondrial protein levels of the F(0)F(1)
      ATPase subunits were normal in hearts with compensated LVR. However, in failing
      hearts, the alpha-subunit decreased by 36%, the beta-subunit decreased by 16%,
      the oligomycin sensitivity-conferring protein subunit decreased by 40%, and the
      initiation factor 1 subunit decreased by 41%. Thus in failing hearts, reductions
      in mitochondrial F(0)F(1)-ATPase protein expression are associated with increased
      myocardial free ADP.

PMID- 11514304
TI  - Temporal effects of 17beta-estradiol on caveolin-1 mRNA and protein in bovine
      aortic endothelial cells.
AB  - Endothelial nitric oxide synthase (eNOS) is regulated both by caveolin-1 and
      17beta-estradiol (E(2)). Temporal relationships between effects of estrogen on
      caveolin-1 and nitric oxide (NO) are not known. Therefore, this study was
      designed to determine whether estrogen regulates caveolin-1 and, if so, whether
      such regulation corresponds to changes in nitrite/nitrate (NO(x)) production.
      Bovine aortic endothelial cells (BAECs) were cultured in the absence and presence
      of 17beta-estradiol or 17alpha-estradiol (10(-8) and 10(-10) M) for 12, 24, and
      48 h. eNOS protein expression and NO(x) production increased significantly after
      24 h but not after 12-h treatment with 17beta- and not 17alpha-estradiol. Both
      mRNA and protein for caveolin-1 were increased significantly only after 48-h
      treatment with E(2), but eNOS protein and NO(x) production were decreased
      compared with cells treated for 24 h. These increases in caveolin-1 were
      inhibited by the estrogen receptor antagonist ICI-182,780 (10(-6) M). Results of
      this study suggest that E(2) stimulates caveolin-1 transcription and translation
      through estrogen receptor-mediated mechanisms. The results further suggest that
      estrogen may indirectly regulate NO(x) through caveolin-1 expression, which
      inhibits eNOS catalytic activity.

PMID- 11514305
TI  - Inhibition of Na+/Ca2+ exchange by KB-R7943: transport mode selectivity and
      antiarrhythmic consequences.
AB  - The Na+/Ca2+ exchanger plays a prominent role in regulating intracellular Ca2+
      levels in cardiac myocytes and can serve as both a Ca2+ influx and efflux
      pathway. A novel inhibitor, KB-R7943, has been reported to selectively inhibit
      the reverse mode (i.e., Ca2+ entry) of Na+/Ca2+ exchange transport, although many
      aspects of its inhibitory properties remain controversial. We evaluated the
      inhibitory effects of KB-R7943 on Na+/Ca2+ exchange currents using the giant
      excised patch-clamp technique. Membrane patches were obtained from Xenopus laevis
      oocytes expressing the cloned cardiac Na+/Ca2+ exchanger NCX1.1, and outward,
      inward, and combined inward-outward currents were studied. KB-R7943
      preferentially inhibited outward (i.e., reverse) Na+/Ca2+ exchange currents. The
      inhibitory mechanism consists of direct effects on the transport machinery of the
      exchanger, with additional influences on ionic regulatory properties. Competitive
      interactions between KB-R7943 and the transported ions were not observed. The
      antiarrhythmic effects of KB-R7943 were then evaluated in an ischemia-reperfusion
      model of cardiac injury in Langendorff-perfused whole rabbit hearts using
      electrocardiography and measurements of left ventricular pressure. When 3 microM
      KB-R7943 was applied for 10 min before a 30-min global ischemic period,
      ventricular arrhythmias (tachycardia and fibrillation) associated with both
      ischemia and reperfusion were almost completely suppressed. The observed
      electrophysiological profile of KB-R7943 and its protective effects on ischemia
      reperfusion-induced ventricular arrhythmias support the notion of a prominent
      role of Ca2+ entry via reverse Na+/Ca2+ exchange in this process.

PMID- 11514306
TI  - Short-term exercise training can improve myocardial tolerance to I/R without
      elevation in heat shock proteins.
AB  - We examined the effects of 3 days of exercise in a cold environment on the
      expression of left ventricular (LV) heat shock proteins (HSPs) and contractile
      performance during in vivo ischemia-reperfusion (I/R). Sprague-Dawley rats were
      divided into the following three groups (n = 12/group): 1) control, 2) exercise
      (60 min/day) at 4 degrees C (E-Cold), and 3) exercise (60 min/day) at 25 degrees
      C (E-Warm). Left anterior descending coronary occlusion was maintained for 20
      min, followed by 30 min of reperfusion. Compared with the control group, both the
      E-Cold and E-Warm groups maintained higher (P < 0.05) LV developed pressure,
      first derivative of pressure development over time (+dP/dt), and pressure
      relaxation over time (-dP/dt) throughout I/R. Relative levels of HSP90, HSP72,
      and HSP40 were higher (P < 0.05) in E-Warm animals compared with both control and
      E-Cold. HSP10, HSP60, and HSP73 did not differ between groups. Exercise increased
      manganese superoxide dismutase (MnSOD) activity in both E-Warm and E-Cold hearts
      (P < 0.05). Protection against I/R-induced lipid peroxidation in the LV
      paralleled the increase in MnSOD activity whereas lower levels of lipid
      peroxidation were observed in both E-Warm and E-Cold groups compared with
      control. We conclude that exercise-induced myocardial protection against a
      moderate duration I/R insult is not dependent on increases in myocardial HSPs. We
      postulate that exercise-associated cardioprotection may depend, in part, on
      increases in myocardial antioxidant defenses.

PMID- 11514307
TI  - Nitric oxide from perivascular nerves modulates cerebral arterial pH reactivity.
AB  - In the isolated rat middle cerebral artery (MCA) we investigated the role of
      nitric oxide (NO)/cGMP in the vasodilatory response to extraluminal acidosis.
      Acidosis increased vessel diameter from 140 +/- 27 microm (pH 7.4) to 187 +/- 30
      microm (pH 7.0, P < 0.01). NO synthase (NOS) inhibition by N(omega)-nitro-L
      arginine (L-NNA, 10 microM) reduced baseline diameter (103 +/- 20 microm, P <
      0.01) and attenuated response to acidosis (9 +/- 8 microm). Application of the NO
      donors 3-morpholinosydnonimine (1 microM) or S-nitroso-N-acetylpenicillamine (1
      microM), or of 8-bromoguanosine 3',5'-cyclic monophosphate (8-BrcGMP, 100 microM)
      reestablished pre-L-NNA diameter at pH 7.4 and reversed L-NNA-induced attenuation
      of the vessel response to acidosis. Restoration of pre-L-NNA diameter (pH 7.4) by
      papaverine (20 microM) or nimodipine (30 nM) had no effect on the attenuated
      response to acidosis. Guanylyl cyclase inhibition with 1H-[1,2,4]oxadiazolo[4,3
      a]-quinoxalin-1-one (5 microM) or NOS-inhibition with 7-nitroindazole (7-NI, 100
      microM) reduced baseline vessel diameter (109 +/- 8 or 127 +/- 11 microm,
      respectively) and vasodilation to acidosis, and restoration of baseline diameter
      with 8-BrcGMP (30 microM) completely restored dilation to pH 7.0. Chronic
      denervation of NOS-containing perivascular nerves in vivo 14 days before artery
      isolation significantly reduced pH-dependent reactivity in vitro (diameter
      increase sham: 48 +/- 14 microm, denervated: 14 +/- 8 microm), and 8-BrcGMP (30
      microM) restored dilation to pH 7.0 (denervated: 49 +/- 31 microm). Removal of
      the endothelium did not change vasodilation to acidosis. We conclude that NO,
      produced by neuronal NOS of perivascular nerves, is a modulator in the pH
      dependent vasoreactivity.

PMID- 11514308
TI  - Coordinate regulation of endothelin and adrenomedullin secretion by oxidative
      stress in endothelial cells.
AB  - To elucidate the significance of oxidative stress in the modulation of
      endothelial functions, we examined the effects of H(2)O(2) on the expression of
      two endothelium-derived vasoactive peptides, endothelin (ET) and adrenomedullin
      (Am), and their interaction. H(2)O(2) dose dependently suppressed ET secretion
      and ET-1 mRNA expression in bovine carotid endothelial cells (ECs). Menadion
      sodium bisulfate, a redox cycling drug, also decreased ET secretion in a dose
      dependent manner. Catalase, a H(2)O(2) reductase, and dl-alpha-tocopherol
      (vitamin E) significantly inhibited H(2)O(2)-induced suppression of ET secretion.
      Downregulation of ET-1 mRNA under oxidative stress was regulated at the
      transcriptional level. In contrast, H(2)O(2) increased Am secretion (and its mRNA
      expression) accompanied by the augmentation of cAMP production. Am, as well as 8
      bromo-cAMP and forskolin decreased ET secretion in a dose-dependent fashion.
      Furthermore, an anti-Am monoclonal antibody that we developed abolished H(2)O(2)
      induced suppression of ET secretion at 6-24 h after the addition of H(2)O(2).
      H(2)O(2) increased the intracellular Ca(2+) concentration ([Ca(2+)](i)).
      Moreover, treatment with ionomycin, a Ca(2+) ionophore, and thapsigargin, an
      inhibitor of endoplasmic reticulum ATPase, decreased ET secretion dose
      dependently for 3 h. These results suggest that the production of ET was
      decreased via activation of the Am-cAMP pathway and by the elevation of
      [Ca(2+)](i) under oxidative stress. These findings elucidate the coordinate
      expression of two local vascular hormones, ET and Am, under oxidative stress,
      which may protect against vascular diseases.

PMID- 11514309
TI  - Existence of cardiac PNMT mRNA in adult rats: elevation by stress in a
      glucocorticoid-dependent manner.
AB  - Phenylethanolamine N-methyltransferase (PNMT) is the enzyme that synthesizes
      epinephrine from norepinephrine. The aim of this study was to determine potential
      PNMT gene expression in the cardiac atria and ventricles of adult rats and to
      examine whether the gene expression of this enzyme is affected by immobilization
      stress. PNMT mRNA levels were detected in all four parts of the heart, with the
      highest level in the left atrium. Both Southern blot and sequencing verified the
      specificity of PNMT detected by RT-PCR. Single immobilization for 2 h increased
      gene expression of PNMT in both atria and ventricles. In atria, this effect was
      clearly modulated by glucocorticoids, because either adrenalectomy or
      hypophysectomy prevented the increase in PNMT mRNA levels in response to
      immobilization stimulus. This study establishes, for the first time, that PNMT
      gene expression occurs in cardiac atria and also, to a small extent, in
      ventricles of adult rats. Immobilization stress increases gene expression in
      atria and ventricles. This increase requires an intact hypothalamus-pituitary
      adrenocortical axis, indicating the involvement of glucocorticoids.

PMID- 11514310
TI  - Shear level influences resistance artery remodeling: wall dimensions, cell
      density, and eNOS expression.
AB  - The magnitude of shear stimulus has been shown to determine the level of growth
      factor expression in cell culture. However, little is known regarding what effect
      shear level has on specific arterial wall remodeling events in vivo. We have
      hypothesized that the rate of luminal diameter change and specific remodeling
      events within the arterial wall layers are dependent on shear level. Selective
      ligations were made to alter the number of microvascular perfusion units of
      mesenteric arteries within the same animal to approximately 50%, 200%, and 400%
      of control. Arterial blood flow and wall shear rate were correlated with the
      degree of alteration in perfusion units. Luminal diameters were decreased in 50%
      arteries by day 2 and increased approximately 17% and 33% respectively, in 200%
      and 400% arteries at day 7. The rate of diameter change was greatest in 50% and
      400% arteries. Wall areas (medial +37%; intimal +18% at day 2) and cell densities
      (intimal +26%; adventitial +44% at day 2) were altered only in the 400% arteries.
      A positive correlation existed by day 2 between endothelial staining for
      endothelial nitric oxide synthase and shear level. The results demonstrate that
      shear level influences the rate of luminal expansion, specific remodeling events
      within each wall layer, and the degree of endothelial gene expression. A greater
      understanding of how shear level influences specific remodeling events within
      each wall layer should aid in the development of targeted therapies to manipulate
      the remodeling process in health and disease.

PMID- 11514311
TI  - Myocardial cross-bridge kinetics in transition to failure in Dahl salt-sensitive
      rats.
AB  - The role of altered cross-bridge kinetics during the transition from cardiac
      hypertrophy to failure is poorly defined. We examined this in Dahl salt-sensitive
      (DS) rats, which develop hypertrophy and failure when fed a high-salt diet (HS).
      DS rats fed a low-salt diet were controls. Serial echocardiography disclosed
      compensated hypertrophy at 6 wk of HS, followed by progressive dilatation and
      impaired function. Mechanical properties of skinned left ventricular papillary
      muscle strips were analyzed at 6 wk of HS and then during failure (12 wk HS) by
      applying small amplitude (0.125%) length perturbations over a range of calcium
      concentrations. No differences in isometric tension-calcium relations or cross
      bridge cycling kinetics or mechanical function were found at 6 wk. In contrast,
      12 wk HS strips exhibited increased calcium sensitivity of isometric tension,
      decreased frequency of minimal dynamic stiffness, and a decreased range of
      frequencies over which cross bridges produce work and power. Thus the transition
      from hypertrophy to heart failure in DS rats is characterized by major changes in
      cross-bridge cycling kinetics and mechanical performance.

PMID- 11514312
TI  - Lipopolysaccharide reduces intercellular coupling in vitro and arteriolar
      conducted response in vivo.
AB  - Our recent in vitro study (Lidington et al. J Cell Physiol 185: 117-125, 2000)
      suggested that lipopolysaccharide (LPS) reduces communication along blood
      vessels. The present investigation extended this study to determine whether any
      effect of LPS and/or inflammatory cytokines [tumor necrosis factor-alpha,
      interleukin (IL)-1beta, and IL-6] on endothelial cell coupling in vitro could
      also be demonstrated for an arteriolar conducted response in vivo. Using an
      electrophysiological approach in monolayers of microvascular endothelial cells,
      we found that LPS (10 microg/ml) but not these cytokines reduced intercellular
      conductance (c(i)) (an index of cell communication) and that LPS together with
      these cytokines did not further reduce c(i). Also, c(i) was restored after LPS
      washout, and the LPS-induced reduction was prevented by protein tyrosine kinase
      (PTK) inhibitors (1.5 microM Tyr A9 and 10 nM PP-2). In our in vivo experiments
      in arterioles of the mouse cremaster muscle, local electrical stimulation evoked
      vasoconstriction that conducted along arterioles. LPS in the muscle superfusate
      did not alter local vasoconstriction but reduced the conducted response. Washout
      of LPS restored the conducted response, whereas PTK inhibitors prevented the
      effect of LPS. On the basis of a newly developed mathematical model, the LPS
      induced reduction in conducted response was predicted to reduce the arteriolar
      ability to increase resistance to blood flow. We conclude that LPS can reduce
      communication in in vitro and in vivo systems comparably in a reversible and
      tyrosine kinase-dependent manner. Based on literature and present results, we
      suggest that LPS may compromise microvascular hemodynamics at both the arteriolar
      responsiveness and the conduction levels.

PMID- 11514313
TI  - Effect of estrogen replacement therapy on distribution of myocardial blood flow
      in female anesthetized rabbits.
AB  - Estrogen replacement therapy reduces risk of cardiovascular events by altering
      coronary vasoregulation and distribution of blood flow. Vessel reactivity and
      blood flow distribution were assessed in anesthetized female rabbits in the
      following groups: 1) sham, 2) ovariectomy, 3) ovariectomy + 17beta-estradiol, and
      4) ovariectomy + dehydroepiandrosterone. After a 2-wk treatment, cardiac
      hemodynamics, vascular reserve, and blood flow were evaluated during the
      following infusions: 1) NaCl, or vehicle (0.5 ml/min), 2) acetylcholine (2
      mg/kg), 3) isoproterenol (2 mg. kg(-1). min(-1)), and 4) chromonar (8 mg/kg). In
      hearts from ovariectomized rabbits, autoregulatory blood flow was preserved
      despite lower diastolic perfusion pressures (55 +/- 8 vs. 64 +/- 8 mmHg in sham)
      and rate-pressure product (14.4 +/- 0.8 vs. 19.3 +/- 0.8 beats/min. mmHg x 10(
      3)). Estrogen replacement therapy restored coronary pressure and reserve, and all
      drugs increased vascular conductance. In conclusion, in hearts from
      ovariectomized rabbits, vascular reserve declined because coronary pressure was
      lower; however, blood flow was preserved at a higher level than expected for
      oxygen demand. Estrogen replacement therapy restores myocardial oxygen supply
      demand indices and returns coronary pressure-flow data to levels observed in
      animals with intact ovaries.

PMID- 11514314
TI  - TCA cycle kinetics in the rat heart by analysis of (13)C isotopomers using
      indirect (1)H.
AB  - This study was designed to test the hypothesis that indirect (1)H[(13)C]
      detection of tricarboxylic acid (TCA) cycle intermediates using heteronuclear
      multiple quantum correlation-total correlation spectroscopy (HMQC-TOCSY) nuclear
      magnetic resonance (NMR) spectroscopy provides additional (13)C isotopomer
      information that better describes the kinetic exchanges that occur between
      intracellular compartments than direct (13)C NMR detection. NMR data were
      collected on extracts of rat hearts perfused at various times with combinations
      of [2-(13)C]acetate, propionate, the transaminase inhibitor aminooxyacetate, and
      (13)C multiplet areas derived from spectra of tissue glutamate were fit to a
      standard kinetic model of the TCA cycle. Although the two NMR methods detect
      different populations of (13)C isotopomers, similar values were found for TCA
      cycle and exchange fluxes by analyzing the two data sets. Perfusion of hearts
      with unlabeled propionate in addition to [2-(13)C]acetate resulted in an increase
      in the pool size of all four-carbon TCA cycle intermediates. This allowed the
      addition of isotopomer data from aspartate and malate in addition to the more
      abundant glutamate. This study illustrates that metabolic inhibitors can provide
      new insights into metabolic transport processes in intact tissues.

PMID- 11514315
TI  - Knockout mice heterozygous for Sod2 show alterations in cardiac mitochondrial
      function and apoptosis.
AB  - Heart mitochondria from heterozygous (Sod2(-/+)) knockout mice have a 50%
      reduction in manganese superoxide dismutase (MnSOD) activity. The decrease in
      MnSOD activity was associated with increased mitochondrial oxidative damage as
      demonstrated by a decrease in the activities of iron sulfhydryl proteins
      sensitive to oxygen stress (aconitase and reduced nicotinamide adenine
      dinucleotide-oxidoreductase). Mitochondrial function was altered in the Sod2(-/+)
      mice, as shown by decreased respiration by complex I and an increase in the
      sensitivity of the permeability transition to induction by calcium and t
      butylhydroperoxide. The increased induction of the permeability transition in
      heart mitochondria from Sod2(-/+.)mice was associated with increased release of
      cytochrome c and an increase in DNA fragmentation. Cardiomyocytes isolated from
      neonatal Sod2(-/+) and Sod2(-/-) mice were more sensitive to cell death than
      cardiomyocytes from Sod2(+/+) mice after t-butylhydroperoxide treatment, and this
      increased sensitivity was prevented by inhibiting the permeability transition
      with cyclosporin A. These experiments demonstrate that MnSOD may play an
      important role in the induction of the mitochondrial pathway of apoptosis in the
      heart, and this appears to occur primarily through the permeability transition.

PMID- 11514316
TI  - Efficiency, efficacy, and adverse effects of adenovirus vs. liposome-mediated
      gene therapy in cardiac allografts.
AB  - Virus- and nonvirus-mediated immunosuppressive cytokine gene therapy prolongs
      cardiac allograft survival in various nonfunctional heart transplant animal
      models, but its cardiac adverse effects have not been addressed. Recently, we
      developed a functional heterotopic heart transplant model in rabbits. For the
      first time, we were able to systematically compare the efficiency, efficacy, and
      adverse effects of optimized adenovirus- and liposome-mediated ex vivo
      interleukin (IL)-10 gene transfer in functional donor hearts. The efficiency of
      liposome-mediated gene transfer was greatly improved in physiologically
      functioning donor hearts and was only three- to fourfold lower than adenovirus
      mediated gene transfer. The efficacy of liposome-mediated IL-10 gene transfer was
      much higher than that mediated by adenovirus. Significant negative inotropic and
      arrhythmogenic adverse effects on transplanted hearts were observed due to viral
      cytotoxicity and immunogenesis, which greatly abated the therapeutic efficacy of
      this first generation adenovirus-mediated gene therapy.

PMID- 11514317
TI  - A novel method to study contraction characteristics of a single cardiac myocyte
      using carbon fibers.
AB  - To facilitate cardiac muscle research, we developed a novel method by which the
      force and length of a single ventricular myocyte can be recorded with a pair of
      carbon graphite fibers attached firmly to both ends. One fiber was stiff, whereas
      the other fiber was compliant to allow the recording of force and shortening
      during twitch contractions. The image of the compliant carbon fiber was projected
      onto a pair of photodiodes, and their output was fed to a piezoelectric
      transducer after variable amplifications to alter the effective compliance of the
      carbon fiber. Thus contraction of the myocyte was induced under virtually
      isometric conditions as well as under auxotonic conditions. We obtained a bell
      shaped relation between the compliance under an auxotonic load and the work
      output of the myocyte, which was directly related to myocyte performance in the
      heart. Because it is easy to attach myocytes to the experimental apparatus, the
      present method would allow us to study cardiac muscle mechanics at the cellular
      and molecular levels.

PMID- 11514318
TI  - Microfocal X-ray CT imaging and pulmonary arterial distensibility in excised rat
      lungs.
AB  - The objective of this study was to develop an X-ray computed tomographic method
      for measuring pulmonary arterial dimensions and locations within the intact rat
      lung. Lungs were removed from rats and their pulmonary arterial trees were filled
      with perfluorooctyl bromide to enhance X-ray absorbance. The lungs were rotated
      within the cone of the X-ray beam projected from a microfocal X-ray source onto
      an image intensifier, and 360 images were obtained at 1 degrees increments. The
      three-dimensional image volumes were reconstructed with isotropic resolution
      using a cone beam reconstruction algorithm. The vessel diameters were obtained by
      fitting a functional form to the image of the vessel circular cross section. The
      functional form was chosen to take into account the point spread function of the
      image acquisition and reconstruction system. The diameter measurements obtained
      over a range of vascular pressures were used to characterize the distensibility
      of the rat pulmonary arteries. The distensibility coefficient alpha [defined by
      D(P) = D(0)(1 + alphaP), where D(P) is the diameter at intravascular pressure
      (P)] was approximately 2.8% mmHg and independent of vessel diameter in the
      diameter range (about 100 to 2,000 mm) studied.

PMID- 11514319
TI  - Bradykinin elicits "second window" myocardial protection in rat heart through an
      NO-dependent mechanism.
AB  - Bradykinin is an important endogenous mediator exerting acute protective effects
      in the ischemic myocardium. The aims of this study were to investigate whether
      exogenously administered bradykinin could evoke delayed myocardial protection and
      to determine whether any protection observed might be dependent on nitric oxide
      (NO) generation. Conscious rats received bradykinin (40 microg/kg iv) or saline,
      preceded 15-20 min earlier by the NO synthase inhibitor N(omega)-nitro-L-arginine
      methyl ester (L-NAME, 10 mg/kg ip) or saline. Twenty-four hours later, hearts
      were Langendorff perfused and subjected to 35 min of regional ischemia and 120
      min of reperfusion. Infarct size was assessed using tetrazolium staining and
      expressed as a percentage of the risk zone. Bradykinin pretreatment reduced the
      infarct-to-risk ratio from 53.5 +/- 3.2% to 29.1 +/- 4.7% (P < 0.01). The
      administration of L-NAME before bradykinin abrogated the delayed protection
      (infarct size 52.3 +/- 5.0%) but alone did not influence infarct size (53.5 +/-
      4.8%). These results are the first to demonstrate that bradykinin can evoke a
      delayed ("second window") enhancement of myocardial tolerance to ischemia, an
      action that is dependent on the early generation of NO.

PMID- 11514320
TI  - Selection and maintenance of the dominant follicle: an introduction.

PMID- 11514323
TI  - Follicle selection in monovular species.
AB  - Follicle deviation is proposed to be the eminent event in follicle selection in
      monovular species. At deviation, the largest follicle establishes dominance
      apparently before the second-largest follicle can reach a similar diameter. In
      cattle, based on diameters of the two follicles at the beginning of deviation,
      the mechanism becomes established in <8 h. An FSH:follicle-coupling hypothesis
      has been supported as the essence of follicle selection. According to the
      hypothesis, the growing follicles cause the FSH decline from the peak of the wave
      stimulating FSH surge until deviation, even though the follicles continue to
      require FSH (two-way functional coupling involving multiple follicles). During
      multiple-follicle coupling, inhibin is the primary FSH suppressant. Near the
      beginning of deviation, the largest follicle secretes increased estradiol, and
      apparently both estradiol and inhibin contribute to the continuing FSH decline;
      only the more-developed largest follicle is able to utilize the low FSH
      concentrations (single-follicle coupling). Deviation is encompassed by a
      transient elevation in LH in heifers and by a component, often distinct, of the
      long ovulatory LH surge in mares. In heifers, receptors for LH appear in the
      granulosa cells of the future dominant follicle about 8 h before the beginning of
      deviation. The LH stimulates the production of estradiol and insulin-like growth
      factor-1. These intrafollicular factors and perhaps others account for the
      responsiveness of the largest follicle to the low concentrations of FSH. The
      smaller follicles have not reached a similar developmental stage and because of
      their continued and close dependency on FSH become susceptible to the low
      concentrations. Thereby, follicle selection is established.

PMID- 11514324
TI  - Differentiation of dominant versus subordinate follicles in cattle.
AB  - Selection of a dominant follicle, capable of ovulating, from among a cohort of
      similarly sized follicles is a critical transition in follicular development. The
      mechanisms that regulate the selection of a species-specific number of dominant
      follicles for ovulation are not well understood. Cattle provide a very useful
      animal model for studies on follicular selection and dominance. During the bovine
      estrous cycle, two or three sequential waves of follicular development occur,
      each producing a dominant follicle capable of ovulating if luteal regression
      occurs. Follicles are large enough to allow analysis of multiple endpoints within
      a single follicle, and follicular development and regression can be followed via
      ultrasonographic imaging. Characteristics of recruited and selected follicles,
      obtained at various times during the first follicular wave, have been determined
      in some studies, whereas dominant and subordinate follicles have been compared
      around the time of selection in others. As follicular recruitment proceeds, mRNA
      for P450 aromatase increases. By the time of morphological selection, the
      dominant follicle has much higher concentrations of estradiol in follicular
      fluid, and its granulosa cells produce more estradiol in vitro than cells from
      subordinate follicles. Shortly after selection, dominant follicles have higher
      levels of mRNAs for gonadotropin receptors and steroidogenic enzymes. It has been
      hypothesized that granulosa cells of the selected follicle acquire LH receptors
      (LHr) to allow them to increase aromatization in response to LH, as well as FSH.
      However, LH does not appear to stimulate estradiol production by bovine granulosa
      cells, and the role of LHr acquisition remains to be determined. Recent evidence
      suggests a key role for changes in the intrafollicular insulin-like growth factor
      (IGF) system in selection of the dominant follicle. When follicular fluid was
      sampled in vivo before morphological selection, the lowest concentration of IGF
      binding protein-4 (IGFBP-4) was more predictive of future dominance than size or
      estradiol concentration. Consistent with this finding, dominant follicles acquire
      an FSH-induced IGFBP-4 protease activity. Thus, a decrease in IGFBP-4, which
      would make more IGF available to interact with its receptors and synergize with
      FSH to promote follicular growth and aromatization, appears to be a critical
      determinant of follicular selection for dominance.

PMID- 11514325
TI  - Follicle selection in primates: "many are called but few are chosen".
AB  - During the follicular phase of humans and most nonhuman primates, a single
      preovulatory follicle usually matures each menstrual cycle. The observation that
      numerous preovulatory follicles may be stimulated to mature when exogenous
      gonadotropins are administered indicates that there must be a precise and highly
      reproducible mechanism by which only one of the many follicles capable of
      ovulating actually does so. The goal of this review is to summarize past and
      current research which indicates that follicle selection in primates is the
      result of an exquisitely sensitive interplay between gonadotropin secretion by
      the pituitary gland, steroid production by the ovary, and maturation-dependent
      alterations of the ovary's responsiveness to gonadotropins.

PMID- 11514326
TI  - Differentiation of the adult Leydig cell population in the postnatal testis.
AB  - Five main cell types are present in the Leydig cell lineage, namely the
      mesenchymal precursor cells, progenitor cells, newly formed adult Leydig cells,
      immature Leydig cells, and mature Leydig cells. Peritubular mesenchymal cells are
      the precursors to Leydig cells at the onset of Leydig cell differentiation in the
      prepubertal rat as well as in the adult rat during repopulation of the testis
      interstitium after ethane dimethane sulfonate (EDS) treatment. Leydig cell
      differentiation cannot be viewed as a simple process with two distinct phases as
      previously reported, simply because precursor cell differentiation and Leydig
      cell mitosis occur concurrently. During development, mesenchymal and Leydig cell
      numbers increase linearly with an approximate ratio of 1:2, respectively. The
      onset of precursor cell differentiation into progenitor cells is independent of
      LH; however, LH is essential for the later stages in the Leydig cell lineage to
      induce cell proliferation, hypertrophy, and establish the full organelle
      complement required for the steroidogenic function. Testosterone and estrogen are
      inhibitory to the onset of precursor cell differentiation, and these hormones
      produced by the mature Leydig cells may be of importance to inhibit further
      differentiation of precursor cells to Leydig cells in the adult testis to
      maintain a constant number of Leydig cells. Once the progenitor cells are formed,
      androgens are essential for the progenitor cells to differentiate into mature
      adult Leydig cells. Although early studies have suggested that FSH is required
      for the differentiation of Leydig cells, more recent studies have shown that FSH
      is not required in this process. Anti-Mullerian hormone has been suggested as a
      negative regulator in Leydig cell differentiation, and this concept needs to be
      further explored to confirm its validity. Insulin-like growth factor I (IGF-I)
      induces proliferation of immature Leydig cells and is associated with the
      promotion of the maturation of the immature Leydig cells into mature adult Leydig
      cells. Transforming growth factor alpha (TGFalpha) is a mitogen for mesenchymal
      precursor cells. Moreover, both TGFalpha and TGFbeta (to a lesser extent than
      TGFalpha) stimulate mitosis in Leydig cells in the presence of LH (or hCG).
      Platelet-derived growth factor-A is an essential factor for the differentiation
      of adult Leydig cells; however, details of its participation are still not known.
      Some cytokines secreted by the testicular macrophages are mitogenic to Leydig
      cells. Moreover, retarded or absence of Leydig cell development has been observed
      in experimental models with impaired macrophage function. Thyroid hormone is
      critical to trigger the onset of mesenchymal precursor cell differentiation into
      Leydig progenitor cells, proliferation of mesenchymal precursors, acceleration of
      the differentiation of mesenchymal cells into Leydig cell progenitors, and
      enhance the proliferation of newly formed Leydig cells in the neonatal and EDS
      treated adult rat testes.

PMID- 11514327
TI  - Differential subcellular distribution of tubulin epitopes in boar spermatozoa:
      recognition of class III beta-tubulin epitope in sperm tail.
AB  - The exposure of tubulin epitopes was studied in ejaculated boar spermatozoa using
      a panel of four monoclonal antibodies specific to the N-terminal or C-terminal
      structural domains of tubulin and three monoclonal antibodies against class III
      beta-tubulin. The specificity of the antibodies was confirmed by immunoblotting.
      Immunocytochemical staining showed that antibodies discriminated between various
      parts of a spermatozoon, and that epitopes of class III beta-tubulin were present
      in the flagellum. A tubulin epitope from the C-terminal domain of beta-tubulin
      was detected in the triangular segment of the postacrosomal part of the sperm
      head. Its distribution changed after an A23187 ionophore-induced acrosome
      reaction, indicating that tubulin participates in the early stages of
      fertilization. Three monoclonal antibodies, TU-20, SDL.3D10, and TUJ1 directed
      against epitopes on the C-terminal end of neuron-specific class III beta-tubulin
      that is widely used as a neuronal marker, stained the flagella. The reactivity of
      TU-20 was further confirmed by absorbing the antibody with the immunizing peptide
      and by immunoelectron microscopy. Immunoblotting after two-dimensional
      electrophoresis revealed that the corresponding epitope was not present on all
      beta-tubulin isoforms. These results suggest that various tubulins are involved
      in the functional organization of the mammalian sperm flagellum and head.

PMID- 11514328
TI  - Cellular turnover in the mammary gland is correlated with systemic levels of
      progesterone and not 17beta-estradiol during the estrous cycle.
AB  - Adult mammary tissue has been considered "resting" with minimal morphological
      change. Here, we reveal the dynamic nature of the nulliparous murine mammary
      gland. We demonstrate specific changes at the morphological and cellular levels,
      and uncover their relationship with the murine estrous cycle and physiological
      levels of steroid hormones. Differences in the numbers of higher-order epithelial
      branches and alveolar development led to extensive mouse-to-mouse mammary
      variations. Morphology (assigned grades 0-3) ranged from a complete lack of
      alveoli to the presence of numerous alveoli emanating from branches.
      Morphological changes were driven by epithelial proliferation and apoptosis,
      which differed between ductal versus alveolar structures. Proliferation within
      alveolar epithelium increased as morphological grade increased. Extensive
      alveolar apoptosis was restricted to tissue exhibiting grade 3 morphology, and
      was approximately 14-fold higher than at all other grades. Epithelial
      proliferation and apoptosis exhibited a positive relationship with serum levels
      of progesterone, but not with 17beta-estradiol. Compared with other estrous
      stages, diestrus was unique in that the morphological grade, epithelial
      proliferation, apoptosis, and progesterone levels all peaked at this stage. The
      regulated tissue remodeling of the mammary gland was orchestrated with mRNA
      changes in specific matrix metalloproteinases (MMP-9 and MMP-13) and specific
      tissue inhibitors of metalloproteinases (TIMP-3 and TIMP-4). We propose that the
      cyclical turnover of epithelial cells within the adult mammary tissue is a sum of
      spatial and functional coordination of hormonal and matrix regulatory factors.

PMID- 11514329
TI  - Cancellous and cortical bone mechanical properties and tissue dynamics during
      pregnancy, lactation, and postlactation in the rat.
AB  - There are substantial changes in maternal skeletal dynamics during pregnancy,
      lactation, and after lactation. The purpose of this study was to correlate
      changes in cortical and cancellous bone mass, structure, and dynamics with
      mechanical properties during and after the first reproductive cycle in rats. Rats
      were mated and groups were taken at parturition, end of lactation and 8 wk after
      weaning, and were compared with age-matched, nulliparous controls. Measurements
      were taken on femoral cortical bone and lumbar vertebral body cancellous bone. At
      the end of pregnancy, there was an increase in cortical periosteal bone formation
      and an increase in cortical volume, but a suppression of turnover in cancellous
      bone with no change in cancellous or cortical mechanical properties. Lactation
      was associated with a decrease in cortical and cancellous bone strength with a
      decrease in bone volume, but an increase in turnover on cancellous and
      endocortical surfaces. After lactation, there was a partial or full restoration
      of mechanical properties. This study demonstrates substantial changes in bone
      mechanics that correlate with changes in bone structure and dynamics during the
      first reproductive cycle in rats. The greatest changes were observed during the
      lactation period with partial or full recovery in the postlactational period.

PMID- 11514330
TI  - Dynamic changes in gene expression along the rat epididymis.
AB  - In the epididymis a series of complex, sequential events transform immature,
      spermatozoa into mature, motile sperm with fertilizing ability. These events are
      not intrinsic to germ cells but rather are a direct result of exposure to, and
      interaction with, the environment created by the epididymal epithelium. Regional
      differences along the epididymis are essential in the establishment of the
      environment required for sperm maturation. Although parts of this process have
      been identified, the molecular basis for the segment-specific differences and how
      they contribute to the process of sperm maturation, are not yet resolved. The
      identification of genes expressed in a region-specific manner will provide
      valuable insight into the functional differences between the regions. To
      characterize gene expression in the different regions of the epididymis,
      microarrays containing 1176 rat cDNAs were used to examine gene expression in the
      initial segment, caput, corpus, and cauda epididymidis of the adult Brown Norway
      rat. Overall, the cauda epididymidis expressed the most genes and the corpus
      epididymidis the fewest. A small percentage of genes (3%) were expressed highly
      (greater than fivefold the average expression on the array) along the tissue.
      Segment-specific gene expression for genes expressed at high levels was observed
      in all epididymal segments except the corpus epididymidis. Of the genes on the
      array, 36% were expressed in all four epididymal segments; expression changes
      that were a minimum of twofold in either direction between adjacent segments are
      discussed. The expression of cathepsins and oxidative stress-related genes was
      investigated. Six of the eight cathepsins on the array (B, C, E, H, L, and K)
      were expressed above twofold background and showed different levels of expression
      along the duct with cathepsin K showing the most dramatic change (i.e., a
      decrease of 87% between the initial segment and the corpus epididymidis). There
      was also differential expression along the epididymis of many genes associated
      with oxidative stress defenses. Using the power of expression array technology,
      we have identified novel transcripts expressed in a segment-specific manner and
      been able to assess how the expression of several selected gene families is
      modulated along the epididymis.

PMID- 11514331
TI  - Activin stimulates proliferation of rat ovarian thecal-interstitial cells.
AB  - There is growing evidence that the function of ovarian theca-interstitial (T-I)
      cells may be modulated by paracrine actions of activin, inhibin, and follistatin.
      Furthermore, either dysregulation, dysfunction, or both, of these peptides may
      play a role in conditions associated with T-I hyperplasia, such as polycystic
      ovary syndrome (PCOS) and hyperthecosis. This study was designed to evaluate the
      role of activin, inhibin, and follistatin in the modulation of T-I cell
      proliferation. Interaction of these peptides with insulin-like growth factor-I
      (IGF-I), a known stimulator of T-I cell proliferation, was also assessed.
      Purified rat T-I cells were cultured for 48 h in chemically defined media and
      with or without activin (3-30 ng/ml), inhibin (3-30 ng/ml), follistatin (100
      ng/ml), and/or IGF-I (10 nM). T-I cell proliferation was assessed using
      radiolabeled thymidine incorporation assay. Activin alone stimulated
      proliferation of T-I cells in a dose-dependent fashion (by up to 320% above
      control; P < 0.001), whereas inhibin alone or follistatin alone had no
      significant effect. Inhibin had also no effect on activin-induced proliferation.
      Follistatin significantly reduced the stimulatory effects of activin and
      decreased proliferation by up to 46% (P < 0.01) below the level attained in the
      presence of activin alone. IGF-I (10 nM), at a dose producing a near-maximal
      effect, increased proliferation by 175% above control (P < 0.001); insulin (10
      nM) increased proliferation by 52% above control (P < 0.03). A combination of IGF
      I (10 nM) and activin (30 ng/ml) resulted in a 1090% increase of proliferation
      above control (P < 0.001); this stimulatory effect was significantly greater than
      that achieved in the presence of either activin alone or IGF-I alone (P < 0.001).
      Similarly, a combination of insulin (10 nM) and activin (30 ng/ml) increased
      proliferation by 506% above control levels. Flow cytometry evaluation revealed
      that activin increased the proportion of actively dividing cells (in S or G2/M
      phase of the cell cycle) by 42% (P < 0.02), whereas IGF-I had no effect on the
      proportion of actively dividing cells. The present findings indicate that an
      activin-follistatin system may be involved in the regulation of the size of
      ovarian thecal-stromal compartment. In view of the synergy between activin and
      IGF-I, and the difference in the effects on the cell cycle distribution,
      stimulation of T-I proliferation by these agents is likely to be mediated via
      separate transduction pathways. Excess activin or insufficient follistatin may
      contribute to T-I hyperplasia.

PMID- 11514332
TI  - Molecular biology of the channel catfish gonadotropin receptors: 2. Complementary
      DNA cloning, functional expression, and seasonal gene expression of the follicle
      stimulating hormone receptor.
AB  - Molecular cloning of the channel catfish FSH receptor is reported together with
      temporal changes in the gene expression throughout a reproductive cycle. A cDNA
      encoding the receptor was isolated from the testis using reverse transcription
      polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends (RACE)
      procedures. The cDNA coded for a 662-amino acid protein that was most identical
      (51%-59%) to salmon gonadotropin receptor I and the FSH receptors of higher
      vertebrates, and less identical to LH receptors and thyrotropin receptors (45%
      49% and 46%-47%, respectively). In addition, PCR analysis of the genomic DNA
      showed the absence of the LH receptor-specific intron. Expression of the channel
      catfish FSH receptor gene was highly restricted to the testis and ovary, except
      for a low-level expression in the spleen. Transfected COS cells expressed an
      active recombinant receptor as determined by the ligand-specific activation of a
      cAMP-responsive reporter gene (luciferase). The recombinant receptor was
      activated by human FSH and, to a small extent, hCG. Seasonal changes in the
      ovarian expression of the FSH receptor gene, examined by measuring the transcript
      abundance by quantitative real-time RT-PCR, showed a rise around the time of
      onset of ovarian recrudescence and a decrease prior to spawning. This pattern of
      seasonal expression of FSH receptor differs significantly from that of the LH
      receptor, which we reported recently. The differential expression of the two
      gonadotropin receptor genes, in addition to the differential secretion of the
      gonadotropic hormones, seem to be critical for the regulation of steroidogenesis
      and other gonadal physiological processes.

PMID- 11514334
TI  - Role of gelatinase on follicular atresia in the bovine ovary.
AB  - Follicular atresia, like follicular growth and ovulation, is characterized by
      excessive tissue remodeling. It is hypothesized that probably one of the tissue
      remodeling enzymes, such as the gelatinases, could be playing an important role
      in this process. The present study was undertaken to determine the role of
      gelatinase on follicular atresia in the cow. Follicles of 2-6 mm in diameter were
      dissected from ovaries, and follicular fluid was categorized according to the
      morphological appearance of the cumulus-oocyte complexes. Gelatinase activity
      within the follicular fluid was analyzed by gelatin zymography, and film in situ
      zymography was employed in order to localize gelatinase. TUNEL was performed on
      cryosectioned ovaries to understand follicular health. The concentrations of
      steroids in follicular fluid were also measured by solid phase fluoroimmunoassay.
      ProMMP-2 was detected in all normal and atretic categories of follicular fluid.
      The active form of MMP-2 and an additional band of proMMP-9 were detected only in
      atretic follicular fluid. Gelatinase activity was recorded in both granulosa
      cells (GCs) and theca cells (TCs) but were found in comparatively higher numbers
      in those follicles that exhibited a thinned and partially detached granulosa
      layer. TUNEL confirmed that apoptosis had commenced in the GCs of follicles of
      the latter category. The estradiol-17beta (E(2)):progesterone (P(4)) ratio was
      found to be significantly lower in atretic follicles than in normal follicles.
      These results suggest a plausible role for gelatinase in follicular health,
      especially the active form of MMP-2 and proMMP-9, and that bovine follicular
      fluid may be a key indicator of atresia.

PMID- 11514333
TI  - Essential role of neutrophils in germ cell-specific apoptosis following
      ischemia/reperfusion injury of the mouse testis.
AB  - This study investigates the role of neutrophils in ischemia-induced
      aspermatogenesis in the mouse. Previous studies in the rat have demonstrated that
      ischemia-inducing testicular torsion followed by torsion repair and reperfusion
      resulted in germ cell-specific apoptosis. This was correlated with an increase in
      neutrophil adhesion to subtunical venules, an increase in reactive oxygen
      species, and increased expression of several apoptosis-associated molecules. In
      the present investigation, wild-type C57BL/6 mice were subjected to various
      degrees and duration of testicular torsion. A torsion of 720 degrees for 2 h
      caused disruption of the seminiferous epithelium and significantly reduced testis
      weight and daily sperm production. An immunohistochemical method specific for
      apoptotic nuclei indicated that these effects were due to germ cell-specific
      apoptosis. An increase in myeloperoxidase (MPO) activity and an increase in the
      number of neutrophils adhering to testicular subtunical venules after torsion
      repair/reperfusion demonstrated an increase in neutrophil recruitment to the
      testis. In contrast, E-selectin knockout mice and wild-type mice rendered
      neutropenic showed a significant decrease in neutrophil recruitment as evidenced
      by MPO activity and microscopic examination of subtunical venules. Importantly,
      germ cell-specific apoptosis was also reduced. Thus, germ cell-specific apoptosis
      is observed after ischemia/reperfusion of the murine testis, and this apoptosis
      is directly linked to the recruitment of neutrophils to subtunical venules.
      Endothelial cell adhesion molecules, particularly E-selectin, play an important
      role in mediating this pathology.

PMID- 11514335
TI  - Expression and regulation of Fas antigen and tumor necrosis factor receptor type
      I in hen granulosa cells.
AB  - It is now well established that vertebrate ovarian follicles undergo atresia via
      apoptosis, a process that is initiated within the granulosa cell layer of
      undifferentiated follicles. Although the exact signals, membrane-bound receptors,
      and associated intracellular signaling pathways leading to apoptosis within
      granulosa cells have yet to be established, it is evident that multiple and
      redundant pathways exist. Fas, together with its ligand, has been the most
      commonly studied death-inducer in the mammalian ovary; however, nothing is
      currently known regarding expression of either Fas or the related tumor necrosis
      factor receptor type 1 (TNFR1), in avian species. Based on characterization of a
      chicken fas partial cDNA, which includes the entire death domain, the deduced
      amino acid sequence shows 37% identity (53% positive) to human Fas. Northern blot
      analysis demonstrates low expression of the 2.0-kilobase fas transcript in most
      tissues, including the granulosa layer, and highest levels are found in the
      spleen, theca tissue, and the postovulatory follicle. Significantly, fas and
      tnfr1 mRNA levels are higher in atretic follicles than in nonatretic,
      prehierarchal (3- to 8-mm diameter) follicles. Moreover, both fas and tnfr1 mRNA
      levels are up-regulated by twofold to eightfold in granulosa cells following
      plating in the presence of fetal bovine serum, with the most dramatic increase
      found in fas expression within prehierarchal follicle granulosa. Coculture with
      transforming growth factor (TGF) beta attenuates this increase for both
      receptors, whereas cAMP attenuates only the up-regulation of fas. By comparison,
      treatment with TGFalpha enhances expression of tnfr1, but not fas, mRNA. Taken
      together, these data are the first to implicate fas as a mediator of granulosa
      cell apoptosis in a nonmammalian vertebrate, and to implicate the protein kinase
      A signaling pathway in down-regulating fas expression. In addition, data provided
      demonstrate the presence of multiple death domain-containing TNFR family members
      simultaneously expressed within hen granulosa cells, each of which may be
      regulated by separate signaling pathways.

PMID- 11514336
TI  - Mares with delayed uterine clearance have an intrinsic defect in myometrial
      function.
AB  - Persistent, postmating endometritis affects approximately 15% of mares and
      results in reduced fertility and sizable economic losses to the horse-breeding
      industry. Mares that are susceptible to postmating endometritis have delayed
      uterine clearance associated with reduced uterine contractility. Unfortunately,
      the mechanism for reduced uterine contractility remains an enigma. The present
      study examined the hypothesis that mares with delayed uterine clearance have an
      intrinsic contractile defect of the myometrium. Myometrial contractility was
      evaluated in vitro by measuring isometric tension generated by longitudinal and
      circular uterine muscle strips in response to KCl, oxytocin, and prostaglandin
      F(2alpha) (PGF(2alpha)) for young nulliparous mares, older reproductively normal
      mares, and older mares with delayed uterine clearance. In addition, intracellular
      Ca(2+) regulation was evaluated using laser cytometry to measure oxytocin
      stimulated intracellular Ca(2+) transients of myometrial cells loaded with a
      Ca(2+)-sensitive fluorescent dye, fluo-4. For all contractile agonists,
      myometrium from mares with delayed uterine clearance failed to generate as much
      tension as myometrium from older normal mares. Oxytocin-stimulated intracellular
      Ca(2+) transients were similar for myometrial cells from mares with delayed
      uterine clearance and from older normal mares, suggesting that the contractile
      defect did not result from altered regulation of intracellular Ca(2+)
      concentration. Furthermore, no apparent age-dependent decline was observed in
      myometrial contractility; KCl-depolarized and oxytocin-stimulated longitudinal
      myometrium from young normal mares and older normal mares generated similar
      responses. However, circular myometrium from young normal mares failed to
      generate as much tension as myometrium from older normal mares when stimulated
      with oxytocin or PGF(2alpha), suggesting possible age-related alterations in
      receptor-second messenger signaling mechanisms downstream of intracellular Ca(2+)
      release. In summary, for mares with delayed uterine clearance, an intrinsic
      contractile defect of the myometrium may contribute to reduced uterine
      contractility following breeding.

PMID- 11514337
TI  - Role of protein synthesis in the development of a transcriptionally permissive
      state in one-cell stage mouse embryos.
AB  - The time of onset of gene transcription in the mouse embryo is temporally
      regulated. A prominent feature of this regulation is a change during the one-cell
      stage from a transcriptionally nonpermissive state to a transcriptionally
      permissive state. During the early one-cell stage, the cytoplasm is either
      inadequate or suppressive for nuclear gene transcription, but by the late one
      cell stage, the cytoplasm acquires the ability to support gene transcription
      either in endogenous nuclei or exogenous nuclei introduced microsurgically. We
      have investigated the role of protein synthesis in this cytoplasmic transition.
      Nuclei from two-cell stage embryos treated with alpha-amanitin were used to
      evaluate the transcriptional permissiveness of late one-cell stage cytoplasm, as
      indicated by the production of transcripts from four genes that are specifically
      transcribed at elevated rates during the two-cell stage. Two of these genes were
      transcribed following nuclear transfer to late one-cell stage cytoplasm, and two
      were not transcribed. Treatment of the recipient cytoplasm with cycloheximide to
      inhibit protein synthesis from the early to the late one-cell stage inhibited the
      transcription of the two genes that were transcribed in the untreated, late one
      cell stage recipients. These results indicate that acquisition of the
      transcriptionally permissive state during the one-cell stage is facilitated by
      protein synthesis, and that the transcriptional permissiveness in the late one
      cell stage cytoplasm is limited to certain genes.

PMID- 11514338
TI  - Gonadotropin and steroid control of granulosa cell proliferation during the
      periovulatory interval in rhesus monkeys.
AB  - Progesterone produced in response to the midcycle gonadotropin surge is essential
      for ovulation and luteinization of the primate follicle. Because cell-cycle
      arrest is associated with the initiation of luteinization, this study was
      designed to determine the dynamics and regulation of granulosa cell proliferation
      by gonadotropin and progesterone during the periovulatory interval in the primate
      follicle. Granulosa cells or ovaries were obtained from macaques undergoing
      controlled ovarian stimulation either before (0 h) or as long as 36 h following
      the administration of an ovulatory hCG bolus with or without a 3beta
      hydroxysteroid dehydrogenase inhibitor with or without a nonmetabolizable
      progestin. The percentage of cells staining positive for Ki-67, a nuclear marker
      for cell proliferation, decreased (P < 0.05) within 12 h of hCG administration in
      a steroid-independent manner. Levels of cyclin D2 and E mRNA did not decline
      during the periovulatory interval; however, cyclin B1 mRNA was reduced
      significantly by 12 h. Steroid depletion increased (P < 0.05) cyclin B1 mRNA at
      both 12 and 36 h post-hCG and was reversible by progestin replacement at 36 h.
      The cyclin-dependent kinase inhibitor p21(Cip1) was transiently increased 12 h
      post-hCG, whereas p27(Kip1) mRNA levels increased at 36 h in a steroid
      independent fashion. These data suggest that a gonadotropin bolus inhibits
      mitosis in granulosa cells early (12 h) in the periovulatory interval, whereas
      progesterone may play a later, antiproliferative role in luteinized cells of
      primates.

PMID- 11514339
TI  - Ovarian stanniocalcin in trout is differentially glycosylated and preferentially
      expressed in early stage oocytes.
AB  - The stanniocalcin (STC) gene was recently found to be widely expressed in fish.
      In this study, we have characterized ovarian STC in the rainbow trout
      (Oncorhynchus mykiss) and cloned the ovarian cDNA. The STC gene expression was
      highest in early stage oocytes and diminished progressively as oocytes developed.
      At the cellular level, ovarian STC gene expression was most abundant in the
      ooplasm of early stage oocytes, but it was also weakly evident in the theca
      layer, interstitial cells, and vitellogenic oocytes. The STC protein was
      distributed in a pattern similar to that of gene expression but was also apparent
      in glycoprotein vesicles, nuclei, multivesicular bodies, and follicles undergoing
      atresia. Cloned cDNAs obtained from the corpuscles of Stannius (CS) and ovarian
      transcripts were nearly identical. However, Western blotting of the partially
      purified proteins revealed that ovarian STC was larger than CS STC. Further
      analysis revealed that ovarian STC had a much larger N-linked carbohydrate moiety
      (approximately 12 kDa) compared to CS STC (approximately 7 kDa), indicating that
      the two hormones were differentially posttranslationally modified. To our
      knowledge, this is the first characterization of STC gene expression, cDNA, and
      protein distribution in the piscine ovary and the first evidence for any
      difference between alternative sources of the hormone in any species.

PMID- 11514340
TI  - Nature of the spermatogenic arrest in Dazl -/- mice.
AB  - Dazl encodes an RNA-binding protein essential for spermatogenesis. Mice that are
      deficient for Dazl are infertile, lacking any formation of spermatozoa, and the
      only germ cells present are spermatogonia and a few spermatocytes. To gain more
      insight regarding the timing of the spermatogenic arrest in Dazl -/- mice, we
      studied the spermatogonial cell types present in testis sections and in
      seminiferous tubular whole mounts. Most of the seminiferous tubular cross
      sections contained A spermatogonia as the most advanced cell type, with only very
      few containing cells up to pachytene spermatocytes. Both 5-bromodeoxy-uridine
      incorporation and mitotic index indicated that the remaining A spermatogonia were
      actively proliferating. C-kit immunohistochemical studies showed that most of the
      A spermatogonia were positively stained for the c-Kit protein ( approximately
      80%). The clonal composition of the A spermatogonia in tubular whole mounts
      indicated these cells to be A(single) (A(s)), A(paired) (A(pr)), and A(aligned)
      (A(al)) spermatogonia. It is concluded that the prime spermatogenic defect in the
      Dazl -/- mice is a failure of the great majority of the A(al) spermatogonia to
      differentiate into A(1) spermatogonia. As a result, most seminiferous tubules of
      Dazl -/- mice only contain actively proliferating A(s), A(pr), and A(al)
      spermatogonia, with cell production being equaled by apoptosis of these cells.

PMID- 11514341
TI  - Effects of second messengers on gap junctional intercellular communication of
      ovine luteal cells throughout the estrous cycle.
AB  - Corpora lutea (CL) from Days 5, 10, and 15 after superovulation were
      enzymatically dispersed, and a portion of the cells were elutriated to obtain
      fractions enriched with small or large luteal cells. Mixed, small, and large
      luteal cell fractions were incubated with no treatment or with agonists or
      antagonists of cAMP (dbcAMP or Rp-cAMPS), protein kinase C (PKC; TPA or H-7), or
      calcium (A23187, EGTA, or A23187 + EGTA). The rate of contact-dependent gap
      junctional intercellular communication (GJIC) was evaluated by laser cytometry.
      Media were collected for progesterone (P(4)) radioimmunoassay, and luteal cells
      cultured with no treatment were fixed for immunocytochemistry or frozen for
      Western blot analysis. Luteal cells from each stage of the estrous cycle
      exhibited GJIC. The dbcAMP increased (P < 0.05) GJIC for all cell types across
      the estrous cycle. The Rp-cAMPS decreased (P < 0.05) GJIC for small luteal cells
      on Day 5 and for all cell types on Days 10 and 15. The TPA inhibited (P < 0.01),
      but H-7 did not affect, GJIC for all cell types across the estrous cycle. The
      A23187 decreased (P < 0.05) GJIC for large luteal cells touching only small or
      only large luteal cells, whereas A23187 + EGTA decreased (P < 0.05) GJIC for all
      cell types across the estrous cycle. For the mixed and large luteal cell
      fractions, dbcAMP increased (P < 0.05), but TPA and A23187 + EGTA decreased (P <
      0.05), P(4) secretion. The A23187 alone decreased (P < 0.05) P(4) secretion by
      large, but not by mixed, luteal cells. For all days and cell types, the rate of
      GJIC and P(4) secretion were correlated (r = 0.113-0.249; P < 0.01). Connexin 43
      was detected in cultured luteal cells by immunofluorescence and Western
      immunoblotting. Thus, intracellular regulators like cAMP, PKC, or calcium appear
      to regulate GJIC, which probably is an important mechanism for coordinating
      function of the ovine CL.

PMID- 11514342
TI  - Capacitation is associated with tyrosine phosphorylation and tyrosine kinase-like
      activity of pig sperm proteins.
AB  - Capacitation represents the final maturational steps that render mammalian sperm
      competent to fertilize, either in vivo or in vitro. Capacitation is defined as a
      series of events that enables sperm to bind the oocyte and undergo the acrosome
      reaction in response to the zona pellucida. Although the molecular mechanisms
      involved are not fully understood, sperm protein phosphorylation is associated
      with capacitation. The hypothesis of this study is that protein tyrosine
      phosphorylation and kinase activity mediate capacitation of porcine sperm. Fresh
      sperm were incubated in noncapacitating or capacitating media for various times.
      Proteins were extracted with SDS, subjected to SDS-PAGE, and immunoblotted with
      an antiphosphotyrosine antibody. An M(r) 32 000 tyrosine-phosphorylated protein
      (designated as p32) appeared only when the sperm were incubated in capacitating
      medium and concomitant with capacitation as assessed by the ionophore-induced
      acrosome reaction. The p32 was soluble in Triton X-100. Fractionation of sperm
      proteins with Triton X-114 demonstrated that after capacitation, this tyrosine
      phosphoprotein is located in both the cytosol and the membrane. Enzyme
      renaturation of sperm proteins was conducted in gels with or without either poly
      glu:tyr (a tyrosine kinase substrate) or kemptide (a protein kinase A substrate).
      An M(r) 32 000 enzyme with kinase behavior was observed in all gels but was
      preferentially phosphorylated on tyrosine, as assessed by phosphorimagery and by
      thin layer chromotography to identify the phosphoamino acids. Indirect
      immunolocalization showed that the phosphotyrosine residues redistribute to the
      acrosome during capacitation, which is an appropriate location for a protein
      involved in the acquisition of fertility.

PMID- 11514343
TI  - Energy status of nonmatured and in vitro-matured domestic cat oocytes and of
      different stages of in vitro-produced embryos: enzymatic removal of the zona
      pellucida increases adenosine triphosphate content and total cell number of
      blastocysts.
AB  - In this study, we evaluated the adenosine triphosphate (ATP) content of
      individual domestic cat oocytes before and after in vitro maturation and of
      different stages of in vitro-produced embryos. To investigate the effects of
      assisted-hatching technique on the ATP content and total cell number, the zona
      pellucida of in vitro-produced blastocysts and expanded blastocysts (recovered
      144 h postinsemination [hpi]) was completely removed by pronase treatment. The
      average (mean +/- SEM) ATP content of nonmatured oocytes (3.47 +/- 0.18 pmol) was
      significantly (P < 0.01) higher than that of in vitro-matured oocytes (2.17 +/-
      0.10 pmol). After in vitro fertilization and culture, the ATP content of two-cell
      stages (24 hpi) was 1.17 +/- 0.08 pmol, which increased to 1.47 +/- 0.19 and 1.88
      +/- 0.32 pmol at the four- (40 hpi) and eight-cell (48 hpi) stages, respectively.
      The ATP content then decreased to 1.48 +/- 0.10 pmol in 16-cell embryos (64 hpi),
      reaching a minimum of 0.49 +/- 0.04 pmol at the morula stage (120 hpi).
      Blastocysts, expanded blastocysts (both 144 hpi), and hatching blastocysts (192
      hpi) revealed ATP levels of 1.05 +/- 0.09, 1.79 +/- 0.01, and 4.17 +/- 0.21 pmol,
      respectively. After enzymatic removal of the zona pellucida (ERZP) at 144 hpi,
      ATP content and total cell numbers of blastocysts (4.15 +/- 0.37 pmol of ATP,
      328.3 +/- 48.5 cells) and expanded blastocysts (5.81 +/- 0.54 pmol of ATP, 430.1
      +/- 29.7 cells) analyzed at 192 hpi were significantly (P < 0.001) higher than in
      their nontreated counterparts (blastocysts: 1.00 +/- 0.09 pmol of ATP, 65.3 +/-
      4.6 cells; expanded blastocysts: 1.79 +/- 0.11 pmol of ATP, 121.4 +/- 6.5 cells).
      Our study describes, to our knowledge for the first time, changes in the energy
      status of domestic cat oocytes before and after maturation and during in vitro
      development after fertilization. The ERZP markedly increased the ATP content and
      total cell number of blastocyst stages, suggesting that this technique may
      improve the quality and viability of in vitro-produced domestic cat embryos.

PMID- 11514344
TI  - Angiotensin II and atrial natriuretic peptide in the cow oviductal contraction in
      vitro: direct effect and local secretion of prostaglandins, endothelin-1, and
      angiotensin II.
AB  - Angiotensin II (Ang II) and atrial natriuretic peptide (ANP) may be involved in
      local regulation of the oviductal contraction during the estrous cycle. Thus, the
      in vitro effects of Ang II and ANP on the secretion and contraction of bovine
      oviduct during the follicular, postovulatory, and luteal phases were
      investigated. An in vitro microdialysis system (MDS) was utilized to determine
      the intraluminal release of prostaglandins (PGs), Ang II, and endothelin-1 (ET-1)
      from the bovine oviducts as well as to observe the effect of Ang II and ANP on
      the local secretion of these substances. The basal release of PGs, ET-1, and Ang
      II was higher (P < 0.05) during the follicular and postovulatory phases than
      during the luteal phase. Stimulation by infusion of Ang II (10(-6) M) or ANP (10(
      7) M) into the MDS was carried out for 4 h between 4 and 8 h of incubation. In
      the oviducts from the follicular and postovulatory phases, the infusion of ANP
      increased the release of Ang II, but not of ET-1. Infusion of Ang II stimulated
      the release of ET-1. Both Ang II and ANP increased PGE(2) and PGF(2alpha)
      release. In the contraction study, direct administration of Ang II (10(-7) M) or
      ANP (10(-8) M) into the medium during the follicular and postovulatory phases
      increased the amplitude of oviductal contraction. In contrast, these substances
      did not show any effect in the contraction and secretion of oviducts from cows
      during the midluteal phase. These results indicate that during the periovulatory
      period, Ang II and ANP stimulate the contractile amplitude of the oviduct in
      vitro. In addition to their direct action on oviductal contraction, Ang II may
      activate oviductal secretion of ET-1 and PGs. Likewise, ANP stimulates oviductal
      secretion of PGs and Ang II. Hence, the overall results suggest the existence of
      a functional endothelin-angiotensin-ANP system in the bovine oviduct during the
      periovulatory period, which may regulate the oviductal contraction to ensure
      maximum efficiency of gamete/embryo transport through the oviduct.

PMID- 11514345
TI  - Maternal reproductive experience enhances early postnatal outcome following
      gestation and birth of rats in hypergravity.
AB  - A major goal of space life sciences research is to broaden scientific knowledge
      of the influence of gravity on living systems. Recent spaceflight and
      centrifugation studies demonstrate that reproduction and ontogenesis in mammals
      are amenable to study under gravitational conditions that deviate considerably
      from those typically experienced on Earth (1 x g). In the present study, we
      tested the hypothesis that maternal reproductive experience determines neonatal
      outcome following gestation and birth under increased (hyper) gravity.
      Primigravid and bigravid female rats and their offspring were exposed to 1.5 x g
      centrifugation from Gestational Day 11 either through birth or through the first
      postnatal week. On the day of birth, litter sizes were identical across gravity
      and parity conditions, although significantly fewer live neonates were observed
      among hypergravity-reared litters born to primigravid dams than among those born
      to bigravid dams (82% and 94%, respectively; 1.0 x g controls, 99%). Within the
      hypergravity groups, neonatal mortality was comparable across parity conditions
      from Postnatal Day 1 through Day 7, at which time litter sizes stabilized.
      Maternal reproductive experience ameliorated neonatal losses during the first 24
      h after birth but not on subsequent days, and neonatal mortality was associated
      with changes in maternal care patterns. These results indicate that repeated
      maternal reproductive experience affords protection against neonatal losses
      during exposure to increased gravity. Differential mortality of neonates born to
      primigravid versus bigravid dams denotes gravitational load as one environmental
      mechanism enabling the expression of parity-related variations in birth outcome.

PMID- 11514346
TI  - Effect of cyclic 3',5'-adenosine monophosphate, glucocorticoids, and insulin on
      leptin messenger RNA levels and leptin secretion in cultured human trophoblast.
AB  - Leptin is a polypeptide hormone originally thought to be produced exclusively by
      adipocytes. However, both leptin mRNA and leptin protein were identified in human
      placental trophoblast cells, suggesting a potential role in human pregnancy. In
      the present report, we examined the regulation of leptin mRNA levels and
      secretion by cAMP, glucocorticoids, and insulin in term human placental tissue.
      Placentae were obtained immediately after delivery from mothers with
      uncomplicated pregnancies. Leptin concentrations were measured by ELISA in the
      cultured media of trophoblast maintained in monolayer culture for 24, 48, and 72
      h. Likewise leptin mRNA levels in these cultured human trophoblast cells were
      determined by reverse transcription-polymerase chain reaction. Treatment with
      forskolin and (Bu)(2) cAMP led to a time- and dose-dependent increase in leptin
      release, significant after 48 and 72 h. Moreover, incubation with forskolin for
      48 h also clearly increased leptin mRNA concentration. Leptin secretion and mRNA
      levels were also assessed after treatment with insulin or dexamethasone. We found
      a time- and dose-dependent increase in leptin release, significant after 48 and
      72 h. Leptin mRNA levels were also increased after these treatments. All this
      supports a stimulatory role of cAMP pathway, insulin and dexamethasone in the
      leptin mRNA levels, and leptin release in trophoblast cells in vitro.

PMID- 11514347
TI  - Muc-1, integrin, and osteopontin expression during the implantation cascade in
      sheep.
AB  - The extracellular matrix protein osteopontin (OPN) is a component of histotroph
      that increases in uterine flushings from pregnant ewes during the peri
      implantation period and is localized on the apical surfaces of the uterine
      luminal epithelium (LE) and conceptus trophectoderm (Tr). The potential
      involvement of OPN in the implantation adhesion cascade in sheep was investigated
      by examining temporal, spatial, and potential functional relationships between
      OPN, Muc-1, and integrin subunits during the estrous cycle and early pregnancy.
      Immunoreactive Muc-1 was highly expressed at the apical surfaces of uterine
      luminal (LE) and glandular epithelium (GE) in both cycling and pregnant ewes but
      was decreased dramatically on LE by Day 9 and was nearly undetectable by Day 17
      of pregnancy when intimate contact between LE and Tr begins. In contrast,
      integrin subunits alpha(v), alpha(4), alpha(5), beta(1), beta(3), and beta(5)
      were constitutively expressed on conceptus Tr and at the apical surface of
      uterine LE and GE in both cyclic and early pregnant ewes. The apical expression
      of these subunits could contribute to the apical assembly of several OPN
      receptors including the alpha(v)beta(3), alpha(v)beta(1), alpha(v)beta(5),
      alpha(4)beta(1), and alpha(5)beta(1) heterodimers on endometrial LE and GE, and
      conceptus Tr in sheep. Functional analysis of potential OPN interactions with
      conceptus and endometrial integrins was performed on LE and Tr cells in vitro
      using beads coated with OPN, poly-L-lysine, or recombinant OPN in which the Arg
      Gly-Asp sequence was replaced with RGE or RAD. Transmembrane accumulation of
      talin or alpha-actinin at the apical surface of uterine LE and conceptus Tr cells
      in contact with OPN-coated beads revealed functional integrin activation and
      cytoskeletal reorganization in response to OPN binding. These results provide a
      physiological framework for the role of OPN, a potential mediator of implantation
      in sheep, as a bridge between integrin heterodimers expressed by Tr and uterine
      LE responsible for adhesion for initial conceptus attachment.

PMID- 11514348
TI  - Failure of spermatogenesis in mice lacking connexin43.
AB  - Connexin43 (Cx43), a gap junction protein encoded by the Gja1 gene, is expressed
      in several cell types of the testis. Cx43 gap junctions couple Sertoli cells with
      each other, Leydig cells with each other, and spermatogonia/spermatocytes with
      Sertoli cells. To investigate the role of this communication pathway in
      spermatogenesis, we studied postnatal testis development in mice lacking Cx43.
      Because such mice die shortly after birth, it was necessary to graft testes from
      null mutant fetuses under the kidney capsules of adult males for up to 3 wk.
      Grafted wild-type testes were used as controls. In our initial experiments with
      wild-type testes, histological examination indicated that the development of
      grafted testes kept pace with that of nongrafted testes in terms of the onset of
      meiosis, but this development required the presence of the host gonads. When
      excised grafts were stimulated in vitro with cAMP or LH, there was no significant
      difference in androgen production between null mutant and wild-type testes,
      indicating that the absence of Cx43 had not compromised steroidogenesis. Previous
      research has shown that Cx43 null mutant neonates have a germ cell deficiency
      that arises during fetal life, and our analysis of grafted testes demonstrated
      that this deficiency persists postnatally, giving rise to a "Sertoli cell only"
      phenotype. These results indicate that intercellular communication via Cx43
      channels is required for postnatal expansion of the male germ line.

PMID- 11514349
TI  - Follicle selection in cattle: follicle deviation and codominance within
      sequential waves.
AB  - Follicle deviation during bovine follicular waves is characterized by continued
      growth of a developing dominant follicle and reduction or cessation of growth of
      subordinate follicles. Characteristics of follicle deviation for waves with a
      single dominant follicle were compared between wave 1 (begins near ovulation; n =
      15) and wave 2 (n = 15). Follicles were defined as F1 (largest), F2, and F3,
      according to maximum diameter. No mean differences were found between waves for
      follicle diameters at expected deviation (F1, > or =8.5 mm; Hour 0) or observed
      deviation or in the interval from follicle emergence at 4.0 mm to deviation. For
      both waves, circulating FSH continued to decrease (P < 0.05) after Hour 0,
      estradiol began to increase (P < 0.05) at Hour 0, and immunoreactive inhibin
      began to decrease (P < 0.05) before Hour 0. A transient elevation in circulating
      LH reached maximum concentration at Hour 0 (P < 0.01) in both waves and was more
      prominent (P < 0.0001) for wave 1. Waves with codominant follicles (both
      follicles >10 mm) were more common (P < 0.02) for wave 1 (35%) than for wave 2
      (4%). Codominants (n = 6) were associated with more (P < 0.05) follicles > or=4
      mm and a greater concentration (P < 0.04) of circulating estradiol at Hours -48
      to -8 than were single dominant follicles (n = 15). A mean transient increase in
      FSH and LH occurred in the codominant group at Hour -24 and may have interfered
      with deviation of F2. In codominant waves, deviation of F3 occurred near Hour 0
      (F1, approximately 8.5 mm). A second deviation involving F2 occurred in four of
      six waves a mean of 50 h after the F3 deviation and may have resulted from a
      greater suppression (P < 0.05) of FSH in the codominant group after Hour 0. In
      conclusion, follicle or hormone differences were similar for waves 1 and 2,
      indicating that the deviation mechanisms were the same for both waves. Waves that
      developed codominant follicles differed in hormone as well as follicle dynamics.

PMID- 11514350
TI  - Epidermal growth factor modulates transforming growth factor receptor messenger
      RNA and protein levels in hamster preantral follicles in vitro.
AB  - Epidermal growth factor (EGF) is mitogenic to preantral follicles, and
      transforming growth factor beta (TGFbeta) influences ovarian cell functions in a
      variety of species. Although an interaction of these ligands during preantral
      folliculogenesis is likely, whether EGF influences TGFbeta action on preantral
      follicles by modulating TGFbeta receptor (TbetaR) gene transcription and
      translation is not known. To determine whether EGF influenced TbetaR mRNA and
      protein levels in granulosa cells during preantral folliculogenesis, hamster
      preantral follicles at stages 1-6 were cultured in the absence or presence of EGF
      and follicular TbetaR mRNA, and protein levels were monitored by semiquantitative
      reverse transcription polymerase chain reaction and immunoblotting, respectively.
      Both TbetaR type I (TbetaRI) and TbetaR type II (TbetaRII) mRNA and protein were
      present in preantral follicles, and their expression was up-regulated by EGF in a
      stage-dependent manner. However, EGF effect on the expression of TbetaRI and
      TbetaRII was differential. In contrast to TbetaRI, EGF-stimulation of follicular
      TbetaRII mRNA expression was evident from stages 1 and 2 onwards, and more than
      twofold induction was noted for stages 4-6. Moreover, significant increases in
      thecal TbetaR mRNA levels were noted for stage 6 follicles. Follicles at smaller
      stages appeared to be more sensitive to EGF than were larger preantral follicles.
      Despite an increase in the cytosolic form of TbetaRI protein for most of the
      stages and TbetaRII protein for follicles at stages 4 and 5, EGF-stimulation of
      the membrane-associated form of the receptor was restricted to follicles at stage
      6. Functionally, TGFbeta1 attenuated EGF-induced DNA synthesis for follicles at
      stages 1-3 and 6 without affecting EGF-induced progesterone production for most
      of the stages. Administration of alpha-amanitin resulted in a significant
      reduction of EGF-induction of TbetaR mRNA levels, suggesting that increased
      receptor protein levels were a consequence of mRNA synthesis. These results
      indicate that an interaction between EGF and TGFbeta forms an important
      regulatory mechanism for preantral folliculogenesis. The effect of EGF on TbetaRI
      and TbetaRII gene transcription and translation are differential, and follicular
      response to EGF depends on the developmental status of the follicles.

PMID- 11514351
TI  - Cellular localization of gelatinases and tissue inhibitors of metalloproteinases
      during follicular growth, ovulation, and early luteal formation in the rat.
AB  - The matrix metalloproteinase (MMP) system consists of a proteolytic component,
      the metalloproteinases, and an associated class of tissue inhibitors of
      metalloproteinases (TIMPs). We investigated the cellular localization of the
      TIMPs and the gelatinase family of MMPs throughout the latter stages of
      follicular growth and during the periovulatory period. Immature female rats were
      injected with eCG, and ovaries were collected at the time of eCG administration
      (0 h) and at 6, 12, 24, or 36 h after eCG injection (i.e., follicular development
      group). A second group of animals (periovulatory) was injected with eCG followed
      by hCG 48 h later, and ovaries were collected at 0, 12, and 24 h after hCG.
      Ovaries were processed for the cellular localization of gelatinase or TIMP mRNA
      or gelatinolytic activity. Gelatinase mRNA (MMP-2 and MMP-9) was localized to the
      theca of developing follicles and to the stroma. Following a hCG stimulus, MMP-2
      mRNA increased as the granulosa cells of preovulatory follicles underwent
      luteinization during formation of the corpus luteum (CL). MMP-9 mRNA remained
      predominantly in the theca during this period. In situ zymography for
      gelatinolytic activity demonstrated a pattern of activity that corresponded with
      the localization of MMP-2 and MMP-9 mRNA around developing follicles.
      Gelatinolytic activity was observed at the apex of preovulatory follicles and
      throughout the forming CL. The mRNA for TIMP-1, -2, and -3 was localized to the
      stroma and theca of developing follicles. TIMP-3 mRNA was present in the
      granulosa cells of certain follicles but was absent in granulosa cells of
      adjacent follicles. At 12 h after hCG, luteinizing granulosa cells expressed TIMP
      1 and TIMP-3 mRNA, but TIMP-2 mRNA was at levels equivalent to the background. In
      the newly forming CL at 24 h after hCG administration, the luteal cells expressed
      TIMP-1, -2, and -3 mRNA, although the pattern of cellular expression was unique
      for each of the TIMPs. These findings demonstrate that the MMPs and TIMPs are in
      the cellular compartments appropriate for impacting the remodeling of the
      extracellular matrix as the follicle grows, ovulates, and forms the CL.

PMID- 11514352
TI  - Ovarian estrogen receptor-beta (ERbeta) regulation: I. Changes in ERbeta
      messenger RNA expression prior to ovulation in the ewe.
AB  - Ovarian growth and development are critically dependent upon the influence of
      endogenous estrogens, and both are highly regulated during the reproductive
      cycle. The observation that estrogen-receptor-alpha-deficient mice still exhibit
      follicular growth and development, together with other evidence, suggests that
      responsiveness of the ovary to estradiol occurs predominantly through the second
      estrogen receptor, ERbeta. We characterized the physiological regulation of
      ERbeta expression in ovarian follicles during the follicular phase of sheep that
      were synchronized for estrus during the breeding season with intravaginal
      progesterone implants (controlled internal drug release [CIDR] device; InterAg,
      Hamilton, New Zealand). Ovaries were removed at times corresponding to the early
      (EF) and late follicular phases (LF) of the ovine estrous cycle (12 h [n = 5] and
      32 h [n = 5] after CIDR device removal, respectively). Sections of ovary were
      then hybridized with a cRNA probe corresponding to the 5' region of ovine ERbeta.
      ERbeta mRNA expression within the granulosa layer of different size follicles
      (size classes: < or =3 mm, 3.1-4.0 mm, 4.1-5.0 mm, >5 mm) was quantified. ERbeta
      mRNA expression varied both with follicle size (P < 0.01) and with cycle stage (P
      < 0.01). In EF ewes, the highest levels of ERbeta mRNA expression were found in
      follicles < or = 3 mm in size. ERbeta mRNA expression declined progressively
      thereafter among the different size classes with lowest levels expressed in >5-mm
      follicles. By contrast, expression of ERbeta mRNA in the 3.1- to 4.0-mm follicles
      of LF group was significantly higher than in the < or =3-mm size follicles and
      declined thereafter progressively to the >5-mm size levels as in the EF group.
      Furthermore, expression of ERbeta mRNA in < or =3-mm size follicles of LF group
      was significantly lower than the corresponding size class in the EF group. Lower
      expression of ERbeta mRNA in >5-mm follicle is suggestive of a down-regulation by
      the local estrogen milieu.

PMID- 11514353
TI  - In vitro production of haploid germ cells from fresh or frozen-thawed testicular
      cells of neonatal bulls.
AB  - Improved methods for culturing spermatogenic cells will facilitate the study of
      spermatogenesis, treatment of male factor infertility, and genetic modification
      of the male germ line. The objective of this study was to develop a procedure for
      achieving male germ cell progression through meiosis in vitro. Testes from 3-day
      old bulls were decapsulated and seminiferous tubules were dissociated
      enzymatically to recover Sertoli and germ cells. Dissociated cells were
      reaggregated by phytohemagglutinin and encapsulated by calcium alginate, then
      cultured for up to 14 wk in modified Dulbecco modified Eagle medium/F12 (32
      degrees C, 5% CO(2) in air). At 2, 5, and 10 wk, cultured cells were examined and
      evaluated by reverse transcription-polymerase chain reaction (RT-PCR) and
      Northern blot analysis for protamine-2 (PRM-2) and transition protein-1 (TP-1)
      mRNA, expressed specifically in round spermatids. Ploidy was characterized by
      flow cytometric analysis of DNA content of cultured cells. Only Sertoli cells and
      gonocytes were observed in seminiferous tubules of 3-day-old testes. By 10 wk of
      culture, small spherical cells (7-10 microm) were apparent at the margin of cell
      associations in culture. Following RT-PCR and Northern blot analysis, specific
      bands corresponding to PRM-2 and TP-1 were detected only in adult testis RNA or
      after 10 wk of culture. Based on flow cytometry, a haploid population of cells
      appeared in vitro that was not in 3-day-old bull testis. The novel culture system
      developed in this study is the first to promote differentiation of gonocytes to
      presumptive spermatids in vitro based on the expression of spermatid-specific
      genes.

PMID- 11514354
TI  - Evidence for a role of capillary pericytes in vascular growth of the developing
      ovine corpus luteum.
AB  - Because of rapid growth followed by spontaneous regression, the ovarian corpus
      luteum (CL) is an excellent model to study angiogenesis in vivo. To evaluate the
      expression of vascular endothelial growth factor (VEGF) protein during luteal
      development, ovaries were collected from FSH-stimulated ewes throughout the
      estrous cycle. VEGF was immunolocalized in tissue sections by using an affinity
      purified antibody. VEGF protein localized exclusively to the thecal layer of
      preovulatory follicles, while the granulosa was devoid of staining. Associated
      with the periovulatory period was intense expression of VEGF by thecal cells at
      the basement membrane and subsequent invasion of the granulosa layers by these
      VEGF-positive cells immediately after ovulation. The early CL showed staining for
      VEGF in thecal-derived compartments, and strong staining for VEGF was also seen
      in cells within the granulosa-derived parenchymal lobules. Dual
      immunohistochemical localization of VEGF and smooth muscle cell alpha-actin
      indicated that the VEGF-positive cells were capillary pericytes or vascular
      smooth muscle cells. In another experiment, we quantified proliferation of
      endothelial cells and pericytes throughout luteal development. Pericytes
      represented a large proportion of the proliferating cells during the early luteal
      phase and then decreased dramatically. Perivascular cells, therefore, may play a
      critical role in angiogenesis that occurs during transformation of the follicle
      into the highly vascular CL of the sheep. As angiogenesis occurs only at the
      level of capillaries, and pericytes are integral members of these microvessels,
      regulation of pericytes may provide a novel mechanism for regulating luteal
      growth and tissue growth in general.

PMID- 11514355
TI  - Cycle-dependent expression of interleukin-1 receptor type II in the human
      endometrium.
AB  - Cytokines such as interleukin-1 (IL-1) play a major role in the reparative and
      inflammatory-like processes that occur in human endometrium during every
      menstrual cycle, but they also seem to be implicated in critical reproductive
      events such as ovulation and implantation. Interleukin-1 is tightly regulated in
      the body by a complex network of control systems. In the present study, we
      examined the expression of IL-1RII, a natural specific inhibitor of IL-1, in the
      human endometrium and found an interesting distribution and temporal pattern of
      expression throughout the menstrual cycle. Immunoreactive IL-1RII was found in
      stromal as well as epithelial cells, but it was predominant within the lumen of
      the glands and the apical side of surface epithelium. In situ hybridization and
      reverse transcription-polymerase chain reaction (RT-PCR) analyses showed higher
      levels of mRNA in epithelial than in stromal cells. The IL-1RII cellular and
      luminal secretion followed a regulated cycle phase-dependent pattern of
      expression. Although elevated in the late proliferative/early secretory phase of
      the menstrual cycle, IL-1RII luminal secretion significantly decreased in the
      midsecretory phase, reaching its lowest levels at Day 21, before augmenting
      markedly again during the late secretory phase. This pattern of expression was
      less obvious at the level of cellular staining, as examined by
      immunohistochemistry, but it was corroborated by Western blot analysis of IL-1RII
      protein and semiquantitative RT-PCR of IL-1RII mRNA in the whole endometrial
      tissue and separated glandular epithelial cells. The reduced expression of IL
      1RII within the implantation window suggests the existence of accurate regulatory
      mechanisms that, by down-regulating IL-1RII expression, alleviate IL-1 inhibition
      during this crucial period and facilitate IL-1 proimplantation actions. The
      elevated expression of IL-1RII observed during the late secretory phase suggests
      an involvement of IL-1RII in control of the proinflammatory state that takes
      place in the endometrium during the premenstrual and menstrual periods.

PMID- 11514356
TI  - Influence of insulin-like growth factor-I and its interaction with gonadotropins,
      estradiol, and fetal calf serum on in vitro maturation and parthenogenic
      development in equine oocytes.
AB  - The effects of insulin-like growth factor-I (IGF-I) and its interaction with
      gonadotropins, estradiol, and fetal calf serum (FCS) on in vitro maturation (IVM)
      of equine oocytes were investigated in this study. We also examined the role of
      IGF-I in the presence or absence of gonadotropins, estradiol, and FCS in
      parthenogenic cleavage after oocyte activation with calcium ionophore combined
      with 6-dimethylaminopurine (6-DMAP), using cleavage rate as a measure of
      cytoplasmic maturation. Only equine cumulus-oocyte complexes with compact cumulus
      and homogenous ooplasm (n = 817) were used. In experiment 1, oocytes were
      cultured in TCM-199 supplemented with BSA, antibiotics, and IGF-I at 0 (control),
      50, 100, 200 ng/ml, at 39 degrees C in air with 5% CO(2), 95% humidity for 36 or
      48 h. In experiment 2, oocytes were cultured with FSH, LH, estradiol, and FCS
      with IGF-I at the concentration that promoted the highest nuclear maturation rate
      in experiment 1. In experiment 3, oocytes from the three experimental groups (IGF
      I; hormones; and IGF-I + hormones) were chemically activated by exposure to
      calcium ionophore followed by culture in 6-DMAP. In experiment 1, IGF-I
      stimulated equine oocyte maturation in a dose-dependent manner with the highest
      nuclear maturation rate at a concentration of 200 ng/ml. No significant effect of
      IGF-I on nuclear maturation was observed in experiment 2. In experiment 3, a
      significant difference in cleavage rate was observed between the hormone + IGF-I
      group (15 of 33; 45.4%) compared with IGF-I (10 of 36; 27.8%) and hormone (4 of
      31; 12.9%) alone (P < 0.05). These results demonstrated that IGF-I has a positive
      effect on nuclear maturation rate of equine oocytes in vitro. The addition of IGF
      I to an IVM medium containing hormones and FCS did not increase nuclear
      maturation, but resulted in a positive effect on cytoplasmic maturation of equine
      oocytes measured by parthenogenic cleavage.

PMID- 11514357
TI  - Interrelationships of porcine X and Y chromosomes with pituitary gonadotropins
      and testicular size.
AB  - Endocrine and testicular responses to unilateral castration on 1, 10, 56, or 112
      days of age were characterized in 132 Chinese Meishan (MS) x White composite (WC)
      crossbred boars in which testicular size associates with a quantitative trait
      locus (QTL) on X chromosome. At 220 days of age, testicles of boars unilaterally
      castrated on Day 1 or 10 weighed more and had greater total daily sperm
      production (DSP) than one testicle of bilaterally intact boars (P < 0.05);
      compensation did not double these two responses. Boars with MS alleles at the X
      chromosome QTL had smaller testicles, darker colored parenchyma, and lower total
      DSP than boars with WC alleles (P < 0.05). The MS alleles engendered greater (P <
      0.05) plasma FSH and LH during puberty than WC alleles. Plasma FSH increased (P <
      0.05) within 48 h of unilateral castration on Days 1, 10, and 56. Subsequent
      increases occurred earlier during puberty (P < 0.05) after unilateral castration
      at younger ages than after unilateral castration at older ages. Pubertal
      increases in plasma FSH and LH were greater (P < 0.05) in boars with MS alleles
      than in those with WC alleles for the X chromosome QTL. Breed of Y chromosome had
      no effect on testicular traits, FSH, testosterone, or estrone. For LH, boars with
      an MS Y chromosome had greater (P < 0.01) plasma LH across all ages than boars
      with a WC Y chromosome. We conclude that a gene or groups of genes that reside on
      the porcine X chromosome regulate testicular development and pubertal
      gonadotropin concentrations.

PMID- 11514358
TI  - Infertility and testicular atrophy in the antiestrogen-treated adult male rat.
AB  - The estrogen receptor-alpha (ERalpha) knockout mouse (alphaERKO) lacks ERalpha
      throughout development; therefore, an adult model for the study of estrogen
      effects in male mice was recently developed using the antiestrogen ICI 182,780.
      However, differences between species have been noted during immunostaining for
      ERalpha in the male tract as well as in response to treatments with
      antiestrogens. Therefore, we developed the antiestrogen model in the adult male
      rat to test, in another species, the hypothesis that estrogen regulates fluid
      reabsorption in efferent ductules. Estrogen receptor in the rat was blocked using
      ICI 182,780 for 100-150 days. Male Sprague-Dawley rats were treated weekly with
      s.c. injections of ICI 182,780 (10 mg) or castor oil (as control). The effects of
      ICI included testicular atrophy and infertility, similar to terminal effects in
      the alphaERKO male. Additionally, ICI induced dilations of the rete testis and
      efferent ductules and a reduction in the height of the ductule epithelium, which
      are changes similar to those in both alphaERKO and ICI-treated mice. One
      difference between species was a large variation in effects on the rat efferent
      ductule epithelium, including a transient increase in the number of periodic acid
      Schiff-positive, lysosomal-like granules. These data confirm that estrogen is
      required for normal function of the efferent ductules and is essential for long
      term fertility in the male rodent.

PMID- 11514359
TI  - Effects of breed, parity, and folic acid supplement on the expression of leptin
      and its receptors' genes in embryonic and endometrial tissues from pigs at day 25
      of gestation.
AB  - Recent evidence has pointed toward a possible role of leptin (Lep) and its
      receptor (Lepr) in early gestation materno-fetal cross-talk. However, in
      gestating sows, exhaustive characterization of leptin mRNA expression in backfat
      and leptin-receptor mRNA expression in endometrial and embryonic tissues is still
      pending. The objectives of this study were to characterize the Lep, Lepr, and
      long Lepr-L isoform mRNA expression according to the breed and parity of
      gestating sows or to specific folic acid (B(9)) + glycine dietary treatments. To
      this end, nulliparous (GT) and multiparous occidental Yorkshire-Landrace (YL)
      sows as well as multiparous Chinese Meishan-Landrace (ML) sows were used. These
      sows were randomly assigned to two different dietary treatments: 0 or 15 ppm of
      B(9) + 0.6% glycine, given from the estrous preceding mating until slaughter on
      Day 25 of gestation. Jugular blood samples were collected at mating and on Day 25
      of gestation and assayed for circulating leptin concentrations. Expression levels
      of Lep in backfat and of Lepr and Lepr-L in endometrial and embryonic tissues
      were performed using semiquantitative reverse transcription-polymerase chain
      reaction. Results demonstrated that on Day 25 of pregnancy, the ML sows showed
      higher concentrations of circulating leptin along with higher backfat thickness
      and higher expression of Lep in backfat tissue. Moreover, in embryonic tissues,
      the mRNA expression levels of Lepr and Lepr-L genes were higher in ML than in YL
      sows. Parity effects were observed for mRNA expression of Lepr in both
      endometrial and embryonic tissues, whereas mRNA levels were higher in YL than in
      GT sows. In addition, embryonic Lepr-L mRNA levels were higher in GT than in YL
      sows, and B(9) + glycine dietary supplement decreased the mRNA expression levels
      of Lep in backfat and of Lepr in embryonic tissues. These decreases were
      independent of breed or parity of the sows. The effect of B(9) + glycine on Lepr
      L mRNA expression levels was only seen in YL sows, whereas the treatment lowered
      Lepr-L expression levels in both endometrial and embryonic tissues. These results
      indicate that leptin and its receptor may play a role during early stages of
      development of the pig embryo-fetus, and that these roles could be modulated
      according to the breed and parity of the sows. Moreover, the effects of B(9) +
      glycine on expression levels of embryonic and endometrial Lepr-L mRNA in YL sows
      may explain the previously reported effects of B(9) on embryo survival rate and
      litter size observed in occidental multiparous sows.

PMID- 11514360
TI  - Role of tumor necrosis factor in preovulatory follicles of swine.
AB  - The effects of tumor necrosis factor (TNF) on cultured porcine granulosa cells
      that were obtained from preovulatory follicles were studied with regard to
      following parameters: 1) TNF receptor type I expression, 2) progesterone receptor
      and transforming growth factor beta receptor type II (TbetaR II) as markers of
      luteinization, 3) proliferation, and 4) apoptosis. For comparative purposes the
      effects of TNF were also studied on insulin/forskolin-treated cells, as this
      treatment is well established to induce luteinization. Cytochemical methods
      followed by semiquantitative analysis were used. Our data show that TNF treatment
      upregulates TNF receptor type I expression in granulosa cells. TNF downregulates
      the expression of TbetaR II of insulin/forskolin-stimulated and of unstimulated
      cells. The progesterone receptor is also downregulated by the cytokine after
      insulin/forskolin-induced luteinization. Supplementation of the medium with TNF
      leads to increased proliferation and at the same time it induces apoptosis. Our
      results indicate that TNF exerts an inhibitory influence on luteinization and
      that TNF influences the balance between follicular growth (proliferation) and
      atresia (apoptosis).

PMID- 11514361
TI  - Prolactin actions in the sheep testis: a test of the priming hypothesis.
AB  - This study investigated whether prolactin (PRL) plays a priming role in the
      testis during the nonmating season and thereby facilitates gonadal reactivation.
      Sexually inactive Soay rams under long days were treated as follows: 1) group C
      (control) received vehicle, 2) group B received bromocriptine to suppress PRL
      secretion, 3) group B + PRL received bromocriptine + ovine PRL to reinstate
      physiological levels of PRL (n = 5/group). Treatments were for 10 wk. The
      photoperiod was then switched to short days to reactivate the reproductive axis.
      Testis diameter and sex skin coloration were recorded, and routine blood samples
      were collected to measure concentrations of FSH, inhibin A, and testosterone (T).
      At the end of the treatments, blood samples were collected every 10 min for 10 h
      to monitor LH pulses and the T-response to exogenous LH, and a testis biopsy was
      collected to assess spermatogenic activity (bromodeoxyuridine [BrDU] method) and
      expression of PRL receptor (reverse transcription-polymerase chain reaction and
      immunocytochemistry). There were no significant differences between groups in
      spermatogenesis (BrDU index) or steroidogenesis (T-response), and no difference
      in the time taken to achieve full testicular redevelopment under short days.
      Testis diameter and inhibin A were marginally increased in group B + PRL.
      Overall, this thorough experiment provides minimal support for the priming
      hypothesis.

PMID- 11514362
TI  - Cloning and characterization of a complementary DNA encoding a human epididymis
      associated disintegrin and metalloprotease 7 protein.
AB  - Mammalian spermatozoa interact with the proteins secreted by the epididymis to
      develop fertility. Transmembrane proteins that possess a disintegrin and
      metalloprotease (ADAM) domains are shown to be closely related to spermatogenesis
      and fertilization. Our previous study demonstrated that GP-83, a glycoprotein
      secreted by the epididymis, was conjugated to mature sperm. In this study, a 2.1
      kilobase (kb) GP-83-expressing insert was isolated from a cDNA library of human
      epididymis by immunoscreening using GP-83-specific antiserum. The 5' end rapid
      amplification of cDNA ends (RACE) and 3'-RACE of the 2.1-kb insert elucidated two
      isoforms of GP-83-encoding cDNA sequences, an alpha-form of 3451 base pairs (bp)
      and beta-form of 2643 bp. Both forms exhibit the same open reading frame of 2262
      bp predicting a peptide of 754 amino acid residues. Deduced amino acid sequence
      revealed signal sequence, prodomain, metalloproteinase, disintegrin, cysteine
      rich, epidermal growth factor-like, transmembrane, and cytoplasmic domains. The
      GP-83-encoding sequence was recognized as human ADAM7 due to significant homology
      to other ADAM7s. According to the DNA sequences elucidated in the Human Genome
      Project, h-ADAM7 was located at chromosome 8p22. Ex vivo expression confirmed
      that h-ADAM7 cDNA did encode GP-83. Northern blot analysis revealed two
      transcripts of 4 kb and 3 kb in the epididymis, but not in testis or other major
      tissues. These results indicate that the GP-83-encoding gene is a human
      epididymis-associated ADAM7 gene (human ADAM7, h-ADAM7) and may be involved in
      the sperm-egg interaction.

PMID- 11514364
TI  - Fertilization of eggs of zebrafish, Danio rerio, by intracytoplasmic sperm
      injection.
AB  - To evaluate the potential for fertilization by sperm injection into fish eggs,
      sperm from zebrafish, Danio rerio, were microinjected directly into egg cytoplasm
      of two different zebrafish lines. To evaluate physiological changes of gametes on
      the possible performance of intracytoplasmic sperm injection (ICSI), four
      different combinations of injection conditions were conducted using activated or
      nonactivated gametes. From a total of 188 zebrafish eggs injected with sperm in
      all treatments, 31 (16%) developed to blastula, 28 (15%) developed to gastrula,
      10 (5%) developed abnormally to larval stages, and another 3 (2%) developed
      normally and hatched. The highest fertilization rate (blastodisc formation) was
      achieved by injection of activated spermatozoa into nonactivated eggs (35%).
      Injections were most effective when performed within the first hour after egg
      collection. Flow cytometric analysis of the DNA content of the developing ICSI
      embryos revealed diploidy, and the use of a dominant pigment marker confirmed
      paternal inheritance. Our study indicates that injection of a single sperm cell
      into the cytoplasm of zebrafish eggs allows fertilization and subsequent
      development of normal larvae to hatching and beyond.

PMID- 11514363
TI  - Molecular analysis of a carbohydrate antigen involved in the structure and
      function of zona pellucida glycoproteins.
AB  - A lactosaminoglycan-associated antigen is associated with a carbohydrate moiety
      of all three zona pellucida (ZP) glycoproteins of pig and rabbit but is absent in
      the mouse and rat. A monoclonal antibody (PS1) recognizing this determinant was
      obtained by immunizing mice with a porcine ZP glycoprotein isoform purified by
      two-dimensional polyacrylamide gel electrophoresis. Conditions known to remove O
      linked or sialic acid carbohydrate moieties (alkaline reduction; O-glycanase or
      neuraminidase enzymatic cleavage) did not remove the carbohydrate epitope.
      However, treatment with endo-beta-glycosidase, endoglycosidase F, or combinations
      of neuraminidase plus beta-galactosidase, totally removed the determinant,
      indicating that it is associated with a poly-N-acetyllactosaminoglycan structure
      present on an N-linked oligosaccharide. Molecular morphology studies using
      immunofluorescence and confocal microscopy techniques demonstrate that the PS1
      antigen is localized at the surface of the ZP. Confirmation of this localization
      was obtained through studies that show that this antibody will inhibit homologous
      sperm binding to the pig ZP. Additional analyses using modular contrast
      microscopy and immunocytochemistry demonstrate that this carbohydrate-associated
      antigen is localized in discrete layers throughout the ZP matrix. These studies
      are the first to demonstrate the presence of a lactosaminoglycan type
      carbohydrate moiety in all three ZP proteins using a monoclonal antibody that
      appears to be involved in sperm recognition and structural organization.

PMID- 11514365
TI  - Effect of activin A on in vitro development of rat preantral follicles and
      localization of activin A and activin receptor II.
AB  - Preantral follicles (140-160 microm) were isolated mechanically from the ovaries
      of 10-day-old rats and cultured in groups of four to six for 6 days in medium
      containing 0, 1, 10, or 100 ng/ml of activin A. Activin stimulated (P < 0.05) the
      growth of preantral follicles in a dose-dependent fashion and enhanced the
      proliferation of preantral, oocyte-free follicular cells. Furthermore, treatment
      with activin induced the majority of follicles to form an antrum-like structure
      and helped to maintain the ultrastructure of these follicles during culture.
      Activin A also induced further changes characteristic of follicle and oocyte
      maturation, such as the elongation of granulosa cells contacting the oocyte and
      migration of the cortical granules to the oocyte cortex. In addition, gene
      expression for activin and activin receptor type II (ActR II) was demonstrated in
      both the oocytes and the somatic cells using the reverse transcription-polymerase
      chain reaction, and immunohistochemical studies demonstrated the presence of
      activin and ActR II proteins in the somatic tissue and, especially, the oocytes
      of these follicles. It is concluded that, in vitro, activin A stimulates the
      growth of rat preantral follicles and promotes antrum formation. Furthermore,
      because activin A and ActR II are synthesized within preantral follicles,
      intrafollicular activin likely plays an important role in early follicular
      development.

PMID- 11514367
TI  - Bench to bedside: the development of rapamycin and its application to stent
      restenosis.

PMID- 11514368
TI  - Serial intravascular ultrasound assessment of the efficacy of intracoronary gamma
      radiation therapy for preventing recurrence in very long, diffuse, in-stent
      restenosis lesions.
AB  - BACKGROUND: The efficacy of coronary gamma-irradiation in preventing recurrent in
      stent restenosis (ISR) is well established. However, brachytherapy may be less
      effective in very long, diffuse ISR lesions. METHODS AND RESULTS: We used serial
      intravascular ultrasound (IVUS) to study patients with long, diffuse ISR lesions
      (length, 36 to 80 mm) who were enrolled in (1) Long WRIST (Washington Radiation
      In-Stent Restenosis Trial), a double-blind, placebo-controlled trial of
      intracoronary gamma-irradiation (15 Gy at 2 mm from the source) and (2) high-dose
      (HD) Long WRIST, a registry that used a dose prescription of 18 Gy at 2 mm from
      the source. IVUS was performed using automated pullback (0.5 mm/s). Stent, lumen,
      and intimal hyperplasia were measured at 2-mm intervals. Complete
      postintervention and follow-up IVUS imaging was available in 30 irradiated and 34
      placebo patients from Long WRIST and in 25 patients from HD Long WRIST. Stent
      length was longer in HD Long WRIST than in placebo or treated patients in Long
      WRIST (P=0.0064 and P=0.0125, respectively). Otherwise, baseline measurements
      were similar. At follow-up, the minimum lumen area was largest in the HD Long
      WRIST patients (4.0+/-1.4 mm(2)); areas were 2.9+/-1.0 mm(2) in irradiated
      patients in Long WRIST and 1.9+/-1.1 mm(2) in placebo patients in Long WRIST
      (P<0.005 for all comparisons). CONCLUSIONS: - Serial IVUS analysis shows that
      gamma-irradiation reduces recurrent in-stent neointimal hyperplasia in long,
      diffuse ISR lesions; however, it is even more effective when given at a higher
      dose.

PMID- 11514369
TI  - Circulating matrix metalloproteinases and their inhibitors in patients with
      Kawasaki disease.
AB  - BACKGROUND: Accelerated matrix breakdown caused by the increased activity of
      matrix metalloproteinases (MMPs) and/or the quantitative imbalance between MMP
      and tissue inhibitor of MMP (TIMP) have been implicated in several pathological
      conditions. MMP and TIMP may also be involved in the destruction of the coronary
      arterial wall and the resultant coronary arterial lesions in Kawasaki disease.
      METHODS AND RESULTS: Plasma levels of MMPs, neutrophil elastase, and TIMPs were
      measured by enzyme-linked immunoassay in 57 patients with Kawasaki disease and no
      coronary arterial lesions (group 1) and in 8 patients with Kawasaki disease and
      coronary arterial lesions (group 2). Blood samples were obtained before and after
      intravenous gamma globulin therapy and in the convalescent stage. Levels of MMPs,
      neutrophil elastase, and TIMPs were significantly higher in Kawasaki disease
      patients before gamma globulin therapy than in 18 age-matched afebrile control
      subjects and 17 age-matched febrile disease control subjects (P<0.01). More
      importantly, the pre-gamma globulin MMP9 level and MMP9/TIMP2 ratio and post
      gamma globulin MMP3 level and MMP3/TIMP1 ratio were significantly higher in group
      2 than in group 1 patients (P<0.05). Although MMP levels in febrile disease
      controls were significantly higher than those of afebrile controls, the MMP/TIMP
      ratios of febrile disease controls and afebrile controls were comparable.
      CONCLUSIONS: These data suggest that patients with Kawasaki disease and high
      levels of MMP and/or MMP/TIMP are susceptible to coronary arterial lesions.
      Studies of the effects of MMP inhibitors on coronary outcome may provide evidence
      that MMP is a viable therapeutic target for the prevention of coronary arterial
      lesions due to Kawasaki disease.

PMID- 11514370
TI  - Coexpression of endothelin-converting enzyme-1 and endothelin-1 in different
      stages of human atherosclerosis.
AB  - BACKGROUND: Endothelin-converting enzyme (ECE)-1 activates endothelin-1 (ET-1)
      and may thus contribute to the regulation of vascular tone and cell growth during
      atherosclerosis. METHODS AND RESULTS: To evaluate ECE-1 immunoreactivity
      concerning big ET-1/ET-1, we performed qualitative and quantitative
      immunohistochemistry in normal internal mammary arteries (n=10), in coronary
      arteries with adaptive intimal fibrosis (n=10), in aortic fatty streaks (n=10),
      and in distinct regions of advanced carotid plaques (n=15). Furthermore, we
      determined ECE-1 activity in the control specimens and in the inflammatory
      intimal regions of carotid plaques. Double immunolabeling showed that ECE-1 was
      present in endothelial cells, vascular smooth muscle cells, and macrophages. All
      ET-1(+) cells were simultaneously ECE-1(+). Most importantly, there were
      significantly more ET-1(+) cells in the intima and media when atherosclerosis was
      in an inflammatory stage than when it was in a noninflammatory stage. Moreover,
      ECE-1 activity was upregulated in the intima of carotid plaques, although
      immunohistochemically, there were no significant differences between the number
      of ECE(+) cells in the different compartments of the arterial wall. CONCLUSION:
      Together with ET-1, ECE-1 is abundantly present in human arteries and at
      different stages of atherosclerotic plaque evolution. The upregulation of the ECE
      1/ET-1 system is closely linked to the presence of chronic inflammation and is
      present in very early stages of plaque evolution. Therefore, enhanced production
      of active ET-1 may substantially contribute to cell growth and the regulation of
      vascular tone in advanced atherosclerotic lesions and in the very early stages of
      plaque evolution, when a plaque is still imperceptible clinically.

PMID- 11514371
TI  - Abciximab readministration: results of the ReoPro Readministration Registry.
AB  - BACKGROUND: Platelet glycoprotein IIb/IIIa blockade with abciximab (ReoPro)
      improves the clinical outcomes of percutaneous coronary intervention. This
      registry was conducted to characterize the effects of repeated administration of
      abciximab during intervention. METHODS AND RESULTS: We recruited 500 consecutive
      patients at 22 centers in the United States who were receiving abciximab for at
      least a second time during percutaneous coronary intervention. Safety was
      measured as the incidence of hypersensitivity reactions, major bleeding, and
      thrombocytopenia. Efficacy was assessed as event-free clinical success. Human
      antichimeric antibody (HACA) responses were also characterized. There were no
      cases of hypersensitivity (95% upper confidence bound, 0.3%), major bleeding, or
      death. Clinical success was 94.4%. Thrombocytopenia occurred in 23 patients
      (4.6%; 95% CI, 2.8% to 6.4%), including 12 (2.4%; 95% CI, 1.1% to 3.7%) who
      developed profound thrombocytopenia (<20x10(9) cells/L). In 2 patients (0.4%),
      profound thrombocytopenia did not develop until after hospital discharge; in 4
      (0.8%), profound thrombocytopenia recurred despite platelet transfusion. Before a
      first readministration, a positive HACA titer was present in 22 of 454 patients
      (4.8%); after a first readministration, an additional 82 of 432 (19.0%) became
      HACA-positive. HACA did not neutralize the in vitro inhibition of platelet
      aggregation by abciximab or correlate with clinical events. CONCLUSIONS: The
      results, including overall rates of thrombocytopenia, were consistent with
      randomized clinical trials of first abciximab treatment. However, there was a
      shift from mild to profound thrombocytopenia, and cases of delayed presentation
      and of recurrent thrombocytopenia were seen. These findings suggest that
      indications and guidelines for first-time use apply to retreatment, particularly
      the systematic monitoring for thrombocytopenia.

PMID- 11514372
TI  - Platelet glycoprotein Ibalpha HPA-2 Met/VNTR B haplotype as a genetic predictor
      of myocardial infarction and sudden cardiac death.
AB  - BACKGROUND: Sudden cardiac death (SCD) is one of the leading manifestations of
      coronary heart disease in early middle age. Platelet glycoprotein (GP) Ib-IX-V
      receptor complexes play a key role in the initial adhesion of platelets to
      collagen during the formation of a coronary thrombus. The HPA-2 (Thr145 Met) and
      VNTR polymorphisms of the gene for GP Ibalpha have been studied previously in
      hospitalized patients with acute coronary syndromes. The significance of these
      polymorphisms in victims of sudden cardiac death is not known. METHODS AND
      RESULTS: The association of these 2 polymorphisms with coronary atherosclerosis,
      coronary artery stenosis, coronary thrombosis, myocardial infarction (MI), and
      SCD was studied in the Helsinki Sudden Death Study, which comprised 2 large
      autopsy series, collected 10 years apart during 1981 to 1982 and 1991 to 1992, of
      700 middle-aged white Finnish men who suffered sudden or violent out-of-hospital
      death. The 2 polymorphisms showed an almost complete linkage disequilibrium. Men
      with acute MI (n=80) and coronary thrombosis (n=65) were more likely to be
      carriers of the HPA-2 Met allele (OR 2.0 and 2.6, respectively, P<0.005 for both)
      than were control subjects who died of noncardiac causes (n=367). In men <55
      years old, the Met allele was overrepresented (OR 2.2) among victims of SCD
      (n=98) compared with control subjects (n=249). In men <55 years old, 17 of 29 men
      with acute MI (58.6%) and 16 of 23 men with coronary thrombosis (69.6%) were
      carriers of the HPA-2 Met allele compared with the 49 of 249 (19.7%) who had died
      of noncardiac causes (ORs 5.6 and 9.2, respectively). Similar associations were
      observed in the separate analyses of both autopsy series. CONCLUSIONS: Our
      results suggest that the HPA-2 Met/VNTR B haplotype of the platelet von
      Willebrand factor and thrombin receptor protein GP Ib-V-IX may be considered to
      be a major risk factor of coronary thrombosis, fatal MI, and SCD in early middle
      age.

PMID- 11514373
TI  - Mechanical unloading restores beta-adrenergic responsiveness and reverses
      receptor downregulation in the failing human heart.
AB  - BACKGROUND: Mechanical unloading of the failing human heart with a left
      ventricular assist device (LVAD) results in clinically documented reversal of
      chamber dilation and improvement of cardiac function. We tested the hypothesis
      that LVAD support normalizes the ability of cardiac muscle to respond to
      sympathetic nervous system stimulation by reversing the downregulation of beta
      adrenergic receptors. METHODS AND RESULTS: Human LV tissue was obtained from
      nonfailing hearts of unmatched organ donors and failing hearts at the time of
      transplantation, with or without LVAD. Baseline contractile parameters and
      inotropic response to a beta-adrenergic agonist were measured in isolated
      trabecular muscles. beta-Adrenergic receptor density was quantified by
      radioligand binding. Results showed a significant increase in the response to
      beta-adrenergic stimulation after LVAD (developed tension increased by 0.76+/
      0.09 g/mm(2) in nonfailing, 0.38+/-0.07 in failing, and 0.68+/-0.10 in
      failing+LVAD; P<0.01), accompanied by an increased density of beta-adrenergic
      receptors (58.7+/-9.6 fmol/mg protein in nonfailing, 26.2+/-3.8 in failing, and
      63.0+/-8.3 in failing+LVAD; P<0.05). These changes were unrelated to the duration
      of support. CONCLUSIONS: Data demonstrate that mechanically supporting the
      failing human heart with an LVAD can reverse the downregulation of beta
      adrenergic receptors and restore the ability of cardiac muscle to respond to
      inotropic stimulation by the sympathetic nervous system. This indicates that
      functional impairment of cardiac muscle in human heart failure is reversible.

PMID- 11514374
TI  - Efficacy of pacing therapies for treating atrial tachyarrhythmias in patients
      with ventricular arrhythmias receiving a dual-chamber implantable cardioverter
      defibrillator.
AB  - BACKGROUND: Although overdrive pacing for treating atrial flutter is well
      established, the efficacy of device-based atrial pacing for treating spontaneous
      atrial tachyarrhythmias in patients with implantable cardioverter defibrillators
      (ICD) is unknown. This study evaluated the efficacy of novel pacing therapies for
      treating atrial tachyarrhythmias in patients receiving a dual-chamber ICD to
      treat ventricular tachyarrhythmias. METHODS AND RESULTS: A Jewel AF ICD was
      implanted in 537 patients with ventricular arrhythmia who were followed for
      11.4+/-8.2 months (74% had a documented history of atrial tachyarrhythmias). The
      device discriminated atrial tachycardia (AT) from atrial fibrillation (AF) on the
      basis of cycle length and regularity, and it used 3 different methods of
      overdrive atrial pacing (Ramp, Burst+, and 50-Hz burst) to treat AT episodes and
      one method (50-Hz burst) to treat AF episodes. Pacing successfully terminated 59%
      of 1500 spontaneous AT episodes in 127 patients and 30% of 880 AF episodes in 101
      patients (P<0.001). With AT and AF episodes combined, pacing efficacy was 48%.
      Pacing efficacy was significantly reduced at AT cycle lengths </=220 ms and AF
      cycle lengths </=160 ms (P<0.01) The median time from pacing to AT/AF termination
      was 1.1 minute for the pacing successes and 96 minutes for the failures
      (P<0.001). CONCLUSIONS: Atrial pacing terminated 48% of AT/AF episodes in
      patients with a history of ventricular arrhythmias. Pacing efficacy was greater
      for device-classified AT than AF. Pacing efficacy was significantly influenced by
      tachycardia cycle length. Successful pacing significantly reduces the time
      required for AT/AF termination.

PMID- 11514375
TI  - Conceptus radiation dose and risk from cardiac catheter ablation procedures.
AB  - BACKGROUND: The aim of the current study was to estimate the conceptus radiation
      dose and risk associated with fluoroscopic imaging during a catheter ablation
      procedure for supraventricular tachycardia performed on the expectant mother.
      METHODS AND RESULTS: Exposure parameters and fluoroscopy times for each
      projection of the cardiac ablation procedure performed in 20 female patients of
      childbearing age were recorded. Radiation doses for a potential conceptus were
      estimated by using dose data obtained in anthropomorphic phantoms simulating
      pregnancy at the first, second, and third trimesters. Dose measurements were
      carried out using thermoluminescent dosimeters. For a typical examination, the
      average radiation dose to the conceptus was <1 mGy in all periods of gestation.
      Average excess fatal cancer was 14.5/10(6) unborn children irradiated during the
      first postconception weeks. Corresponding values for the second and third
      trimesters were 30 and 55.7/10(6), respectively. The risk for hereditary effects
      in future generations was 1.5/10(6) cases for conceptus irradiation during the
      first postconception weeks. Corresponding values for the second and third
      trimesters were 3.0 and 5.6/10(6), respectively. Formulas and dose data are
      presented for estimating the conceptus risk from any technique and x-ray system
      used for catheter ablation procedures. CONCLUSIONS: A typical catheter ablation
      procedure results in a very small increase in risk of harmful effects to the
      conceptus. However, estimation of conceptus dose from catheter ablation
      procedures is always needed to assess the risk to the individual developing in
      utero.

PMID- 11514376
TI  - Cerebral autoregulatory responses to head-up tilt in normal subjects and patients
      with recurrent vasovagal syncope.
AB  - BACKGROUND: The effect of orthostatic stress on dynamic cerebral autoregulation
      (CA) in normal subjects and patients with recurrent vasovagal syncope (VVS) is
      unclear. This study assessed the dynamic CA responses of both groups to head-up
      tilt. METHODS AND RESULTS: Seventeen patients with recurrent VVS and 17 pair
      matched control subjects underwent 70 degrees head-up tilt for up to 30 minutes.
      Bilateral middle cerebral artery blood flow velocities (CBFV) were measured with
      transcranial Doppler ultrasound along with noninvasive beat-to-beat blood
      pressure (BP), heart rate, and transcutaneous and end-tidal CO(2) concentrations.
      Indices of dynamic CA were derived for periods before, during, and after tilt.
      Eight normal subjects who developed VVS in an identical protocol but who had no
      previous clinical history of syncope were also studied. CBFV and transcutaneous
      and end-tidal CO(2) levels declined significantly during head-up tilt in all
      groups (P<0.0001). Dynamic CA indices were unchanged throughout tilt in
      nonsyncopal control subjects and were initially unchanged in patients but
      deteriorated significantly in patients and syncopal control subjects in the
      minutes before (P=0.027 and P=0.012, respectively) and after (P=0.002 and
      P=0.007, respectively) syncope. CONCLUSIONS: Dynamic CA is preserved in patients
      and control subjects initially after head-up tilt. Autoregulatory function
      remains intact in nonsyncopal control subjects during prolonged orthostasis but
      deteriorates in patients and syncopal control subjects immediately before and
      after VVS.

PMID- 11514377
TI  - Predisposition to vasovagal syncope in subjects with blood/injury phobia.
AB  - BACKGROUND: Most subjects with blood/injury phobia experience syncope or
      presyncope as part of the phobic response. We tested the hypothesis that these
      subjects have a constitutional autonomic dysregulation that predisposes them to
      vasovagal syncope during head-up tilt. METHODS AND RESULTS: We studied 11
      subjects (9 females, 2 males) who had a history of syncope or presyncope only in
      response to a blood or injury stimulus and 11 healthy matched controls (10
      females, 1 male) without a history of syncope. Blood pressure (BP) and heart rate
      (HR) were measured during a 15-minute baseline period with subjects in the supine
      position and then during 45 minutes of head-up tilt to 70 degrees. Measurements
      at rest did not differ between the blood phobic and control subjects. During
      tilt, 9 (82%) of the 11 blood phobic subjects experienced presyncope or syncope,
      leading to termination of the study after 22+/-17 minutes of tilt. Only 1 (9%) of
      the 11 control subjects experienced presyncope (chi(2)=11.7, P=0.001).
      Hemodynamic responses to tilt were consistent with a vasovagal mechanism in the
      blood phobic subjects, with simultaneous decreases in BP and HR during tilt.
      During tilt, systolic BP fell by 21+/-15 mm Hg (P=0.001), and HR fell by 22+/-25
      bpm (P=0.01). By contrast, BP and HR were very stable in the control group.
      CONCLUSIONS: Subjects with syncope related to blood/injury phobia have an
      underlying autonomic dysregulation predisposing them to neurally mediated
      syncope, even in the absence of any blood or injury stimulus. Fainting related to
      these stimuli may in large part be due to dysfunction in neural circulatory
      control, which may secondarily lead to the phobia because of repeated syncopal
      events.

PMID- 11514378
TI  - Development of a noninvasive ultrasound color M-mode means of estimating
      pulmonary vascular resistance in pediatric pulmonary hypertension: mathematical
      analysis, in vitro validation, and preliminary clinical studies.
AB  - BACKGROUND: Accurate determination of pulmonary vascular resistance (PVR) is an
      important component in the evaluation and treatment of pediatric patients with
      pulmonary hypertension. We developed a novel technique, based on the concept of
      flow propagation, to estimate PVR noninvasively. The hypothesis is that changes
      in PVR cause changes in the velocity propagation (Vel(prop)) within the main
      pulmonary artery and that Vel(prop) can be quantified using color M-mode imaging.
      METHODS AND RESULTS: We tested the hypothesis using mathematical modeling, in
      vitro experiments, and preliminary clinical studies. The mathematical model
      showed that pressure and velocity tracings are closely correlated in time and
      that 6 to 18 ms time resolution was needed to resolve propagation times within
      typical main pulmonary artery lengths (2 to 5 cm). The in vitro experiments
      demonstrated that it was feasible to use color M-mode to measure Vel(prop) and
      that Vel(prop) correlated well with downstream resistance [y=(-1.01x)+22.77;
      R=0.96]. The method was then evaluated on patients undergoing acute pulmonary
      reactivity testing (n=22 measurements). Good correlation between Vel(prop) and
      PVR was found [y=(-1.71x)+26.0; R=0.90; SEE=2.41]. CONCLUSION: This newly
      developed method promises to be useful in the noninvasive evaluation of adults
      and children with pulmonary hypertension.

PMID- 11514379
TI  - Immunopathogenesis of atherosclerosis: endotoxin accelerates atherosclerosis in
      rabbits on hypercholesterolemic diet.
AB  - BACKGROUND: On the basis of our concept that atherosclerosis has an
      immunopathological background, we tested whether activation of the innate immune
      system influences its progression. METHODS AND RESULTS: Hypercholesterolemic
      (0.5% wt/wt diet) rabbits received either repeated intravenous injections of
      endotoxin (Escherichia coli lipopolysaccharide 1.25 to 2.5 microg, once per week)
      or a self-limiting cutaneous Staphylococcus aureus infection with or without a
      quinolone antibiotic. Measured laboratory parameters, including LDL and HDL
      cholesterols, were similar in the different groups of hypercholesterolemic
      animals. All endotoxin-treated animals developed transient episodes of fever
      after endotoxin administration. The extent of atherosclerosis was evaluated by
      computer-assisted morphometry in the aortas en face (Sudan IV) and by histology
      at 8 weeks after start of the experiments. Endotoxin-treated animals exhibited
      significantly accelerated atherosclerosis compared with control animals (141+/-38
      versus 45+/-16 mm(3) total lesion volume, n=7 to 9 rabbits each, P<0.001).
      CONCLUSIONS: Nonspecific stimulation of the innate immune system accelerates
      cholesterol-induced atherosclerosis. These data support the concept that
      atherosclerosis has an immunopathological component and render it improbable that
      a single infectious agent should assume particular importance in its initiation
      or progression.

PMID- 11514380
TI  - Overexpression of functionally coupled cyclooxygenase-2 and prostaglandin E
      synthase in symptomatic atherosclerotic plaques as a basis of prostaglandin E(2)
      dependent plaque instability.
AB  - BACKGROUND: Studies have implicated a role for prostaglandin (PG) E(2)-dependent
      matrix metalloproteinase (MMP) biosynthesis in the rupture of atherosclerotic
      plaque. Cyclooxygenase-2 (COX-2) and PGE synthase (PGES) are coregulated in
      nucleated cells by inflammatory stimuli. The aim of this study was to
      characterize the expression of COX-2 and PGES in carotid plaques and to correlate
      it with the extent of inflammatory infiltration and MMP activity and with
      clinical features of patients' presentation. METHODS AND RESULTS: Plaques were
      obtained from 50 patients undergoing carotid endarterectomy and divided into 2
      groups (symptomatic and asymptomatic) according to clinical evidence of recent
      transient ischemic attack or stroke. Plaques were analyzed for COX-2, PGES, MMP
      2, and MMP-9 by immunocytochemistry and Western blot, whereas zymography was used
      to detect MMP activity. Immunocytochemistry was used to identify CD68+
      macrophages, CD3+ T lymphocytes, and HLA-DR+ cells. The percentage of macrophage
      rich areas was larger (P<0.0001) in symptomatic plaques. COX-2, PGES, and MMPs
      were detected in all specimens; enzyme concentration, however, was significantly
      higher in symptomatic plaques. COX-2, PGES, and MMPs were especially noted in
      shoulders of symptomatic plaques, colocalizing with HLA-DR+ macrophages. All
      symptomatic plaques contained activated forms of MMPs. Finally, inhibition of COX
      2 by NS-398 was accompanied by decreased production of MMPs that was reversed by
      PGE(2). CONCLUSIONS: This study demonstrates the colocalization of COX-2 and PGES
      in symptomatic lesions and provides evidence that synthesis of COX-2 and PGES by
      activated macrophages is associated with acute ischemic syndromes, possibly
      through metalloproteinase-induced plaque rupture.

PMID- 11514381
TI  - Stent coating with titanium-nitride-oxide for reduction of neointimal
      hyperplasia.
AB  - BACKGROUND: Coronary stents prevent constrictive arterial remodeling but
      stimulate neointimal hyperplasia. Stainless steel induces a metallic foreign body
      reaction, which is absent for titanium. The hypothesis of the present study was
      that titanium renders the stent surface biologically inert, with reduced platelet
      and fibrinogen binding. METHODS AND RESULTS: Twelve pigs were instrumented with a
      stainless steel and 2 titanium-nitride-oxide-coated stents (TiNOX 1, ceramic;
      TiNOX 2, metallic). Animals were restudied after 6 weeks. Histological specimens
      of stented segments were analyzed by digital morphometry. Platelet adhesion and
      fibrinogen binding studies were performed in the perfusion chamber. Under in
      vitro conditions, TiNOX 1 showed reduced platelet adhesion (65+/-3%) compared
      with TiNOX 2 (72+/-5%; P<0.05) and stainless steel (71+/-4%; P<0.05). Platelet
      adhesion 48 hours after incubation with human plasma, however, was not different
      between TiNOX 1 (17+/-3%) and 2 (15+/-3%) but was significantly higher with
      stainless steel (23+/-2%; P<0.05). Fibrinogen binding was significantly reduced
      with TiNOX 2 (54+/-3%) compared with TiNOX 1 (82+/-4%, P<0.05) or stainless steel
      (100%, P<0.05). Histomorphometry revealed a significantly larger neointimal area
      in stainless steel (2.61+/-1.12 mm(2)) than in TiNOX 1-coated (1.47+/-0.84 mm(2),
      P<0.02) or TiNOX 2-coated (1.39+/-0.93 mm(2), P<0.02) stents. The reductions were
      44% and 47%, respectively. CONCLUSIONS: TiNOX coating significantly reduces
      neointimal hyperplasia in stainless steel stents. The antiproliferative effect
      was similar for both TiNOX coatings, suggesting that the electrochemical
      properties are more important for attenuation of neointimal proliferation than
      the observed differences in platelet adhesion and fibrinogen binding.

PMID- 11514382
TI  - Macrophage accumulation associated with rat cardiac allograft rejection detected
      by magnetic resonance imaging with ultrasmall superparamagnetic iron oxide
      particles.
AB  - BACKGROUND: Acute cardiac allograft rejection continues to be the cause of graft
      loss and contributes to the morbidity and mortality after cardiac
      transplantation. In this study, we report a new method for detecting organ
      rejection in transplantation with an MR-based technique using dextran-coated
      ultrasmall superparamagnetic iron oxide (USPIO) particles. These particles (
      approximately 27 nm in diameter) are known to shorten relaxation times in MRI
      experiments. METHODS AND RESULTS: A new rat model of heterotopic heart and lung
      transplantation has been developed for MRI experiments. Allotransplantations (DA-
      >BN) were performed (n=8), with syngeneic transplantations (BN-->BN) serving as
      controls (n=8). MR images were obtained with a gradient echo method. At
      postoperative day 7, allotransplants developed moderate rejection as determined
      histopathologically. A significant reduction in MR signal intensity was observed
      after USPIO injection into rats with allotransplanted hearts. Syngeneic
      transplants showed no differences in MR signal intensity before and after USPIO
      injections. After injection of USPIO particles at postoperative day 6, a group of
      allotransplanted rats was treated with cyclosporin A (3 mg/kg). Animals treated
      with cyclosporin A for 7 days showed no reduction in MR signal intensity after
      USPIO reinjection at day 14, whereas animals treated for 4 days showed a
      significant decrease in MR signal intensity in the transplanted hearts indicative
      of acute graft rejection. Pathological analysis of these animals revealed that
      dextran-coated USPIO particles were taken up by the infiltrating macrophages that
      accumulated within the rejecting cardiac graft. CONCLUSIONS: This MRI method
      offers promise as a noninvasive method for detecting transplant allograft
      rejection.

PMID- 11514383
TI  - Cardioprotective effects of ramipril and losartan in right ventricular pressure
      overload in the rabbit: importance of kinins and influence on angiotensin II type
      1 receptor signaling pathway.
AB  - BACKGROUND: The role of kinins in the cardioprotective effects of ACE inhibitors
      remains controversial. METHODS AND RESULTS: Right ventricular pressure overload
      in rabbits was produced by pulmonary artery banding for 21 days. Rabbits were
      untreated, or they received the ACE inhibitor ramipril with or without bradykinin
      B(1) and B(2) receptor blockers or the angiotensin (Ang) II type I (AT(1))
      receptor blocker losartan. Pulmonary artery banding caused right ventricular
      hypertrophy, depressed papillary muscle contractility, and loss of Ang II
      contractile effects because of a signaling defect downstream of AT(1) receptors.
      Paradoxically, AT(1) receptor density and G protein alpha subunits alphaq and
      alphai1/2 increased. Inotropic responsiveness to the alpha-receptor agonist
      phenylephrine was normal. Ramipril preserved cardiac contractility, but this
      effect was attenuated by simultaneous use of kinin receptor blockers. Ramipril
      also maintained responsiveness to Ang II and prevented AT(1) receptor and G
      protein upregulation. The simultaneous use of a kinin receptor blocker attenuated
      but did not prevent upregulation in the AT(1) receptor and G protein. Losartan
      had no effect on baseline contractility, but it maintained cardiac inotropic
      responsiveness to Ang II, prevented upregulation of AT(1) receptors, but did not
      modify G protein upregulation. CONCLUSIONS: Pressure overload of the right
      ventricle decreases contractility, uncouples AT(1) receptors to downstream
      signaling pathways, and changes the expression of components of the AT(1)
      receptor signaling pathway. Ramipril attenuates these effects via kinins.
      Interventions that prevent local increases in Ang II or block AT(1) receptors
      also prevent decreased responsiveness of the AT(1) receptor in this model.

PMID- 11514384
TI  - Angiotensin-converting enzyme inhibitor preserves p21 and endothelial nitric
      oxide synthase expression in monocrotaline-induced pulmonary arterial
      hypertension in rats.
AB  - BACKGROUND: Pulmonary arterial hypertension (PAH) is associated with structural
      changes in the pulmonary vasculature characterized by the proliferation of
      cellular components of the vessels. ACE inhibitor (ACEI) may have beneficial
      effects in treating PAH, but its precise mechanism of action in the remodeling
      process is unclear. p21 is a cyclin-dependent kinase inhibitor that may have a
      protective role in this process by inhibiting cellular proliferation. Endothelial
      nitric oxide synthase (eNOS) has also been shown to be protective by its
      vasodilatory effect. Therefore, we investigated whether expression of p21 and
      eNOS was modulated by ACEI treatment in a rat model. METHODS AND RESULTS:
      Monocrotaline (MCT) was administered to 2 groups of Sprague-Dawley rats fed a
      high-cholesterol diet, ie, one group received MCT concomitantly with enalapril
      treatment (MCT(+)/ACEI(+) rats), and the other group did not receive enalapril
      (MCT(+)/ACEI(-) rats). After 5 weeks, MRI showed right ventricular hypertrophy in
      MCT(+)/ACEI(-) rats. MCT(+)/ACEI(+) rats showed a preserved right ventricular
      morphology. Isolated pulmonary perfusion studies showed that ACEI significantly
      upregulated NO production, as measured by nitrite levels. Addition of N-methyl-D
      glucamine dithiocarbamate-Fe solution, an NO-trapping agent, reversed the basal
      vasodilatory effect of ACEI in the pulmonary vasculature. Immunoblot analysis
      showed decreased p21 and eNOS expression in the lung in MCT(+)/ACEI(-) rats,
      whereas their expression was preserved with enalapril treatment. CONCLUSIONS:
      ACEI suppresses the development of MCT-induced PAH in rats. The mechanism of
      action might involve the preservation of p21 and eNOS expression. Both p21 and
      endothelium-derived NO appear to have protective roles in the development of PAH.

PMID- 11514385
TI  - Density and kinetics of I(Kr) and I(Ks) in guinea pig and rabbit ventricular
      myocytes explain different efficacy of I(Ks) blockade at high heart rate in
      guinea pig and rabbit: implications for arrhythmogenesis in humans.
AB  - BACKGROUND: Class III antiarrhythmic agents commonly exhibit reverse frequency
      dependent prolongation of the action potential duration (APD). This is
      undesirable because of the danger of bradycardia-related arrhythmias and the
      limited protection against ventricular tachyarrhythmias. The effects of blockade
      of separate components of delayed rectifier K(+) current (I(K)) may help to
      develop agents effective at high heart rate. METHODS AND RESULTS: We assessed the
      density and kinetics of the 2 components of the delayed rectifier K(+) current,
      I(Kr) and I(Ks), in rabbit and guinea pig ventricular myocytes. The effects of
      their specific blockers (chromanol 293B for I(Ks) and E-4031 for I(Kr)) on the
      action potential was studied at different heart rates by use of whole-cell patch
      clamp techniques. In guinea pig ventricular myocytes only, blockade of I(Ks)
      causes APD prolongation in a frequency-independent manner, whereas blockade of
      I(Ks) in rabbit ventricular myocytes shows reverse frequency dependence, as does
      blockade of I(Kr) in both species. This result can be explained primarily by the
      higher density of I(Ks) in guinea pig ventricle and by its slow deactivation
      kinetics, which allows I(Ks) to accumulate at high heart rate because little time
      is available for complete deactivation of it during diastole. CONCLUSIONS:
      Density and kinetics of components of I(K) explain why blockade of I(Ks) is more
      effective at high heart rate in the guinea pig ventricle than in the rabbit
      ventricle, without adverse effects at low heart rate.

PMID- 11514386
TI  - Methods for determining the refractory period and excitable gap during persistent
      atrial fibrillation in the goat.
AB  - BACKGROUND: Recently, the temporal excitable gap during atrial fibrillation (AF)
      has been identified as a vulnerable parameter for cardioversion of AF. In this
      study, we evaluated 5 methods to measure the refractory period (RP(AF)) and the
      excitable period (EP(AF)) during persistent AF. METHODS AND RESULTS: In 11 goats
      instrumented with 83 epicardial atrial electrodes, persistent AF (43+/-34 days)
      was induced with a median AF cycle length (CL) of 98+/-14 ms. To measure RP(AF),
      premature stimuli were applied to the center of the electrode array on the right
      or left atrium. The RP(AF) measured by mapping of premature stimuli was 70+/-12
      ms ("gold standard"). The RP(AF) determined during entrainment of AF was 77+/-17
      ms (R(2)=0.88, P<0.01). Statistical analysis of the effects of synchronized
      stimuli (each coupling interval x100) on the AFCL histogram yielded an RP(AF) of
      70+/-13 ms (R(2)=0.94, P<0.01). A further simplification was to apply slow fixed
      rate pacing (1 Hz) during AF. For each stimulus (n=250 to 500), the paced AFCL
      was plotted against its coupling interval, and capture was determined by
      statistical shortening of the AFCL (RP(AF) 71+/-17 ms, R(2)=0.84, P<0.01). The
      5th percentile of the AFCL histogram as an index of RP(AF) was 77+/-12 ms
      (R(2)=0.90, P<0.01). CONCLUSIONS: During persistent AF with an AFCL of 98+/-14
      ms, the RP(AF) determined by mapping of synchronized premature stimuli (gold
      standard) was 70+/-12 ms, with an excitable period of 28+/-8 ms. Although the
      indirect methods to measure RP(AF) all correlated well with the gold standard,
      slow fixed-rate pacing seems to be the most attractive technique because of the
      ease of acquiring the data and the clear graphic result.

PMID- 11514387
TI  - Coordinated adaptation of oxygen transport in cardiopulmonary disease.

PMID- 11514388
TI  - Unique ECG finding in a patient with an axial blood flow pump..

PMID- 11514389
TI  - Acute total occlusion of the right coronary artery by a pellet.

PMID- 11514390
TI  - Quantification of circulating DNA: in the preparation lies the rub.

PMID- 11514391
TI  - Evolution of methods for measurement of HDL-cholesterol: from ultracentrifugation
      to homogeneous assays.
AB  - BACKGROUND: Adoption of automated homogeneous assays for HDL-cholesterol (HDL-C)
      is increasing, driven by the need of clinical laboratories to cope with
      increasing workloads while containing costs. However, performance characteristics
      of homogeneous assays often differ in important aspects from those of the earlier
      precipitation methods. This review provides an overview of the new generation of
      homogeneous assays for HDL-C within the historical context of the evolution of
      methods and the efforts to standardize measurements of the lipoproteins.
      APPROACH: This is a narrative review based on method evaluations conducted in the
      laboratories of the authors as well as on relevant publications, especially
      comparative evaluation studies, from the literature. Publications considered here
      have been collected by the authors over the past 30 years of involvement as
      methods for HDL-C made the transition from their early use in lipid research
      laboratories to clinical laboratories and the recent emergence of homogeneous
      assays. CONTENT: The presentation includes descriptions of methodologies,
      including homogeneous, precipitation, electrophoresis, and ultracentrifugation
      assays. Reference methods and recommended approaches for assessing accuracy are
      described. Accuracy and imprecision are summarized in the context of the National
      Cholesterol Education Program (NCEP) standards for analytical performance. The
      effects of interfering substances and preanalytical sources of variation are
      presented. SUMMARY: Homogeneous assays have been shown to be reasonably well
      suited for use in routine clinical laboratories, generally meeting the NCEP
      criteria for precision, accuracy, and total error. However, discrepant results
      compared with the reference methods have been observed with some of the assays,
      and the sources of discrepancies are not well characterized. Some homogeneous
      reagents have not been thoroughly evaluated. At least three of the reagents have
      experienced successive adjustments in formulation; hence, the reagents may not
      yet be fully optimized. For these reasons, the homogeneous assays cannot be
      confidently recommended for use in long-term clinical trials and other research
      applications without thorough validation.

PMID- 11514392
TI  - Laboratory investigation of thrombophilia.
AB  - Until recently, laboratory diagnosis of thrombophilia was based on investigation
      of the plasmatic anticoagulant pathways to detect antithrombin, protein C, and
      protein S deficiencies and on the search for dysfibrinogenemia and anti
      phospholipid antibodies/lupus anticoagulants. More recently, laboratory
      investigations have been expanded to include activated protein C (APC)
      resistance, attributable or not to the presence of the factor V Leiden mutation;
      hyperprothrombinemia attributable to the presence of the prothrombin gene
      mutation G20210A; and hyperhomocysteinemia attributable to impairment of the
      relevant metabolic pathway because of enzymatic and/or vitamin deficiencies. All
      of the above are established congenital or acquired conditions associated with an
      increased risk of venous and, more rarely, arterial thrombosis. Testing is
      recommended for patients who have a history of venous thrombosis and should be
      extended to their first-degree family members. Because most of the tests are not
      reliable during anticoagulation, it is preferable to postpone laboratory testing
      until after discontinuation of treatment. Whenever possible, testing should be
      performed by means of functional assays. DNA analysis is required for the
      prothrombin gene mutation G20210A. Laboratory diagnosis for anti-phospholipid
      antibodies/lupus anticoagulant should be performed by a combination of tests,
      including phospholipid-dependent clotting assays and solid-phase anti-cardiolipin
      antibodies. Hyperhomocysteinemia can be diagnosed by HPLC methods or by
      fluorescence polarization immunoassays.

PMID- 11514393
TI  - Effects of blood-processing protocols on fetal and total DNA quantification in
      maternal plasma.
AB  - BACKGROUND: Recently, apoptotic cells have been found in plasma obtained by
      centrifugation of blood from pregnant women, raising the question of what
      constitutes plasma and whether plasma is truly cell free. We compared the effects
      of different blood-processing protocols on the quantification, DNA composition,
      and day-to-day fluctuation of fetal and total DNA in maternal plasma. METHODS:
      Blood samples were collected from healthy pregnant women. The blood sample from
      each individual was simultaneously processed by different means, including the
      following: Percoll separation, centrifugation, microcentrifugation, and
      filtration. The resulting plasma aliquots were subjected to real-time
      quantitative amplification of the beta-globin (for total DNA) and SRY (for fetal
      DNA) genes. The differences in the beta-globin and SRY DNA concentrations and the
      degree of variation between the various plasma aliquots were assessed
      statistically. RESULTS: Different protocols of blood processing significantly
      affected the quantification and the day-to-day fluctuation of total (P <0.001),
      but not fetal (quantification, P = 0.336; fluctuation, P = 0.206), DNA in
      maternal plasma. The quantitative difference could be attributed to the fact that
      efficacies of different protocols for generating cell-free plasma vary.
      Processing blood samples by centrifugation followed by filtration or
      microcentrifugation is effective in producing cell-free plasma. CONCLUSIONS:
      Standardization in plasma-processing protocols is needed for maternal plasma DNA
      analysis, especially for quantification of total DNA in maternal plasma. Such
      preanalytic factors may also affect other applications of plasma DNA analysis.

PMID- 11514394
TI  - Genotyping energy-transfer-cassette-labeled short-tandem-repeat amplicons with
      capillary array electrophoresis microchannel plates.
AB  - BACKGROUND: Genetic analysis of microsatellite DNA is a powerful tool used in
      linkage analysis, gene mapping, and clinical diagnosis. To address the expanding
      needs of studies of short tandem repeats (STRs), we demonstrated high-performance
      STR analysis on a high-throughput microchannel plate-based platform. METHODS:
      Energy-transfer-cassette-labeled STR amplicons were separated and typed on a
      microfabricated 96-channel radial capillary array electrophoresis (CAE)
      microchannel plate system. Four-color detection was accomplished with a laser
      excited confocal fluorescence rotary scanner. RESULTS: Multiplex STR analysis
      with single base-pair resolution was demonstrated on denaturing polyacrylamide
      gel media. The high-throughput multiplex capabilities of this genetic analysis
      platform were demonstrated by the simultaneous separation of STR amplicons
      representing 122 samples in ninety-six 5.5-cm-long channels in <8 min. Sizing
      values obtained for these amplicons on the CAE microchannel plate were comparable
      to those measured on a conventional commercial CAE instrument and exhibit <1%
      sizing variance. CONCLUSIONS: Energy-transfer-cassette labeling and
      microfabricated CAE microchannel plates allow high-performance multiplex STR
      analyses.

PMID- 11514395
TI  - Diagnosis of trisomy 21 in fetal nucleated erythrocytes from maternal blood by
      use of short tandem repeat sequences.
AB  - BACKGROUND: The purpose of this study was to determine whether aneuploid fetal
      nucleated erythrocytes (NRBCs) could be detected in maternal blood through the
      use of fluorescent PCR amplification with polymorphic short tandem repeat (STR)
      markers as an alternative or complementary method to analysis by fluorescent in
      situ hybridization (FISH). METHODS: Peripheral blood samples were obtained from
      women who had just undergone termination of pregnancy because of fetal trisomy 21
      (three cases, 47,XY,+21; four cases, 47,XX,+21). Candidate fetal cells were
      isolated by flow-sorting by antibodies to the gamma chain of fetal hemoglobin and
      Hoechst 33342. FISH analysis was performed by the use of chromosome-specific
      probes for X, Y, and 21. Fetal NRBCs, as defined by the presence of gamma
      staining, characteristic morphology, and three chromosome 21 signals, along with
      maternal leukocytes, defined as gamma negative and two chromosome 21 signals,
      were micromanipulated separately and subjected to fluorescent PCR amplification
      of chromosome 21 STR markers (D21S11, D21S1411, and/or D21S1412). RESULTS: In
      five of seven cases analyzed, fetal NRBCs were aneuploid, as determined by the
      presence of triallelic or diallelic peaks of chromosome 21 sequences when
      compared with sequences from the maternal leukocytes. CONCLUSIONS: Fluorescent
      PCR amplification of STRs can detect fetal aneuploidy and may be useful in the
      setting of poor hybridization efficiency with FISH analysis. These results
      suggest that combined fetal aneuploidy and single-gene diagnoses by the use of
      DNA microarrays may be feasible in the near future.

PMID- 11514396
TI  - Quantitative measurement of porphobilinogen in urine by stable-isotope dilution
      liquid chromatography-tandem mass spectrometry.
AB  - BACKGROUND: Measurement of porphobilinogen (PBG) is useful in the diagnosis of
      the acute neurologic porphyrias. Currently used colorimetric assays lack
      analytical and clinical sensitivity and specificity. METHODS: We developed a
      liquid chromatography-electrospray tandem mass spectrometry (LC-MS/MS) method for
      the measurement of PBG in 1 mL of urine, using 5-(aminoethyl)-4-(carboxymethyl)
      1H-2,4-[(13)C]pyrolle-3-propanoic acid ([2,4-(13)C]PBG; 2.75 microg) as internal
      standard. After solid-phase extraction, LC-MS/MS analysis was performed in the
      selected-reaction monitoring (SRM) mode. PBG and [2,4-(13)C]PBG were monitored
      through their own precursor and product ion settings (m/z 227 to 210 and m/z 229
      to 212, respectively). The retention time of PBG and [2,4-(13)C]PBG was 1.0 min
      in a 2.3-min analysis. RESULTS: Daily calibrations (n = 6) between 0.1 and 2.0
      mg/L were linear and reproducible. Inter- and intraassay CVs were 3.2-3.5% and
      2.6-3.1%, respectively, at mean concentrations of 0.24, 1.18, and 2.15 mg/L. The
      regression equation for the comparison between an anion-exchange column method
      (y) and the LC-MS/MS method (x) was: y = 0.84x + 0.74 (S(y/x) = 5.8 mg/24 h; r =
      0.85; n = 100). In 47 volunteers, PBG excretion was 0.02-0.42 mg/24 h, lower than
      reported reference intervals (up to 2.0 mg/24 h) based on colorimetric methods.
      In 85 samples with PBG < or =0.5 by LC-MS/MS, 8 (9.4%) had values > or =2.0 mg/24
      h by the anion-exchange method (mean +/- SD, 4.3 +/- 1.8 mg/24 h). In 11 patients
      with confirmed diagnoses of acute porphyria and increased PBG by LC-MS/MS, 2 had
      values within the reported reference intervals by a quantitative anion-exchange
      method. CONCLUSIONS: The quantitative LC-MS/MS method for PBG measurement
      exhibits greater analytical specificity and improved clinical sensitivity and
      specificity than currently available methods.

PMID- 11514397
TI  - Complete scanning of the hereditary hemochromatosis gene (HFE) by use of
      denaturing HPLC.
AB  - BACKGROUND: Between 4% and 35% of hereditary hemochromatosis (HC) probands are
      C282Y or H63D heterozygotes or lack both of these two common HFE mutations, and
      15 novel HFE mutations have been described recently. We evaluated denaturing HPLC
      (DHPLC) for screening of the whole HFE coding region and further defined whether
      HC probands with an incomplete HFE genotype carry uncommon mutations. METHODS:
      Analytical conditions for each coding exon were determined by a combination of
      computer melting profile predictions and experimental melting curves. To test
      accuracy for scanning the complete HFE coding region and optimize DHPLC running
      conditions, each melting domain was investigated with at least one mutation or
      one polymorphism as reference. We tested 100 DNA samples harboring the C282Y,
      H63D, or S65C mutations and 17 artificially created positive controls that
      carried either 1 of the 14 other known HFE mutations or 3 selected polymorphisms.
      RESULTS: Investigations on each of the coding exons 1, 2, 4, 5, and 6 could be
      performed at one analysis temperature. Coding exon 3 displayed a more complex
      melting profile and required two analysis temperatures. DHPLC detected all known
      HFE mutations as well as the three selected polymorphisms. CONCLUSIONS: DHPLC can
      be used to scan the HFE gene in HC probands in whom at least one chromosome lacks
      an assigned mutation.

PMID- 11514398
TI  - Mitochondrial gene mutations in the tRNA(Leu(UUR)) region and diabetes:
      prevalence and clinical phenotypes in Japan.
AB  - BACKGROUND: Mitochondrial gene mutations play a role in the development of
      diabetes mellitus. We have assessed the frequency of the A3243G and other
      mitochondrial mutations in Japan and in the relationship to clinical features of
      diabetes. METHODS: DNA was obtained from peripheral leukocytes of 240 patients
      with diabetes mellitus (39 with type 1; 188 with type 2; 13 with gestational
      diabetes) and 125 control subjects. We used PCR-restriction fragment length
      polymorphism analysis (ApaI) for A3243G and PCR-single-strand conformation
      polymorphism analysis to determine the mutations in the mitochondrial gene
      including nucleotide position 3243. RESULTS: The A3243G mutation was found in
      seven patients, and an inverse relationship was observed between the degree of
      heteroplasmy and the age at onset of diabetes. A3156G, G3357A, C3375A, and T3394C
      were detected in addition. Those who shared the same mutation showed similar
      clinical characteristics, thus representing a putative clinical subtype. The
      patients with A3156G had a sudden onset of hyperglycemia and showed a rapid
      progression to an insulin-dependent state with positive anti-glutamic acid
      decarboxylase antibody. Those with T3394C showed a mild defect in glucose
      stimulated insulin secretion, and hyperglycemia appeared after adding such
      factors as aging or obesity. CONCLUSIONS: The identification of mitochondrial
      gene mutations allows preclinical diagnosis of diabetes and prediction of the age
      at onset by evaluating the degree of heteroplasmy in cases with A3243G. Mutation
      detection may also be important for patient management and identification of
      affected family members.

PMID- 11514399
TI  - Detection of antinuclear antibodies by use of an enzyme immunoassay with nuclear
      HEp-2 cell extract and recombinant antigens: comparison with immunofluorescence
      assay in 307 patients.
AB  - BACKGROUND: A new enzyme immunoassay (EIA) for automated detection of antinuclear
      antibodies (ANAs) uses a mixture of HEp-2 cell extracts and multiple recombinant
      nuclear antigens immobilized on beads. We compared this EIA and an
      immunofluorescence (IF) assay in a large group of patients and controls. METHODS:
      We studied 492 healthy individuals and 307 patients with connective tissue
      diseases (CTDs). Sera were tested by an automated EIA (COBAS Core HEp2 ANA EIA;
      Roche Diagnostics) and IF. Samples were also tested for eight disease-specific
      antibodies, including antibodies against U1RNP, Sm, SSA/Ro, SSB/La, Scl-70, Jo-1,
      dsDNA, and centromere. RESULTS: Areas under ROC curves for the EIA were greater
      than (P = 0.008-0.012) or numerically identical to areas for the IF method for
      each of six CTDs studied. ROC areas for EIA were 0.98 (95% confidence interval,
      0.95-0.99), 0.99 (0.96-1.00), and 0.99 (0.98-1.00) in systemic lupus
      erythematosus (n = 111), systemic sclerosis (n = 39), and mixed connective tissue
      disease (n = 33), respectively. For all 258 CTD patients with conditions other
      than rheumatoid arthritis (RA), the sensitivity and specificity of the IF method
      at a cutoff dilution of 1:40 were 92% and 65%, respectively, vs 93% and 79% for
      the EIA at a cutoff of 0.6. For the IF method at a cutoff dilution of 1:160,
      sensitivity and specificity were 81% and 87%, respectively, vs 84% and 94%,
      respectively, for the EIA at a cutoff of 0.9. For 207 sera containing at least
      one of eight disease-specific ANAs, positivities for the EIA and the IF method
      were 97.1% and 97.6%, respectively, at cutoffs of 0.6 and 1:40 (P = 0.76).
      CONCLUSIONS: An EIA that can be performed by a fully automated instrument
      distinguishes CTDs (except RA) from healthy individuals with both higher
      sensitivity and specificity than the IF method when the cutoff index was set at
      0.9. Moreover, it can be used to exclude the presence of disease-specific ANAs by
      setting the cutoff index at 0.6 with almost the same efficacy as the IF method.

PMID- 11514400
TI  - Is the thrombopoietin assay useful for differential diagnosis of
      thrombocytopenia? Analysis of a cohort of 160 patients with thrombocytopenia and
      defined platelet life span.
AB  - BACKGROUND: Thrombopoietin (TPO), the major hormone controlling platelet
      production, has been measured in thrombocytopenias with discordant results. The
      aim of our work was to assess the value of the TPO assay for differential
      diagnosis of thrombocytopenias in a large cohort of patients classified according
      to the results of their platelet isotopic study. METHODS: We measured TPO (R&D
      Systems) in serum of 160 thrombocytopenic patients referred to our department for
      platelet life span isotopic studies. We classified patients as follows: (a)
      idiopathic or autoimmune thrombocytopenia group (ITP; patients with increased
      platelet destruction and shortened platelet life span; n = 67); (b) pure genetic
      thrombocytopenia group (patients with decreased platelet production, normal
      platelet life span, and without bone marrow aplasia; n = 55); (c) bone marrow
      aplasia group (BM; patients with decreased platelet production, normal platelet
      life span, and bone marrow aplasia; n = 13). RESULTS: In patients with pure
      genetic thrombocytopenia, TPO (median, 55 ng/L) was not different from TPO in
      patients with ITP (median, 58 ng/L) or controls (n = 54; median, 51 ng/L). Only
      in patients with bone marrow aplasia was TPO significantly higher (median, 155
      ng/L) and negatively correlated to the platelet count (r(2) = 0.5014).
      CONCLUSIONS: Although the median serum TPO is increased in thrombocytopenia with
      decreased platelet production from bone marrow aplasia, it does not differentiate
      patients with pure genetic thrombocytopenia from those with ITP.

PMID- 11514401
TI  - Association of increased ferritin with premature coronary stenosis in men.
AB  - BACKGROUND: Body iron status has been implicated in atherosclerotic
      cardiovascular disease. The main hypothesis is that high iron status is
      associated with increased oxidation of LDL. We investigated the potential role of
      ferritin as an additional risk factor promoting atherosclerosis among a young
      population with coronary artery disease (CAD). METHODS: Four hundred consecutive
      patients (218 males, 182 females) referred for diagnostic coronary angiography
      were examined, and risk factors for CAD, lipids, C-reactive protein (CRP), and
      ferritin concentrations were recorded for all participants. RESULTS: Ferritin was
      higher in the male patients with CAD (121 microg/L; range, 56-258 microg/L) than
      in the men without significant CAD (73 microg/L; range, 32-138 microg/L; P
      <0.002). Multiple logistic regression analysis, after adjustment for the
      established coronary risk factors, showed ferritin as an independent
      discriminating risk factor for CAD (P <0.01). Men in the highest quartile of
      ferritin had an odds ratio (OR) of 1.62 [95% confidence interval (95% CI), 1.12
      2.42; P <0.01] compared with men in the lowest quartile of ferritin. The
      association between ferritin and CAD was more pronounced in male patients < or
      =50 years (OR = 2.65; 95% CI, 1.35-5.51; P <0.003). Ferritin was significantly
      higher in diabetic male patients in comparison with nondiabetic male patients
      [168 microg/L (range, 74-406 microg/L) vs 106 microg/L (range, 44-221 microg/L),
      respectively; P <0.002]. No association was observed between ferritin and CAD
      among the female patients. CONCLUSION: Our data suggest that increased ferritin
      might be an independent predictor of premature CAD in male Iranian patients.

PMID- 11514402
TI  - Instability of lipoprotein(a) in plasma stored at -70 degrees C: effects of
      concentration, apolipoprotein(a) genotype, and donor cardiovascular disease.
AB  - BACKGROUND: There is considerable evidence to suggest that plasma lipoprotein(a)
      [Lp(a)] concentration is a cardiovascular risk factor. Confusing results in
      epidemiologic studies, however, suggest that the effects of storage should be
      further investigated. The influence of the assay method, the initial plasma Lp(a)
      concentration, and the apolipoprotein(a) [apo(a)] genotype are all factors that
      should be considered. METHODS: Blood was obtained from 65 survivors of premature
      myocardial infarction and 95 age-matched controls. The plasma samples were stored
      in sterile conditions at -70 degrees C for 5 years in the presence of antioxidant
      and antiproteolytic substances. Plasma Lp(a) was measured by immunoturbidimetry,
      and apo(a) alleles were determined by pulsed-field gel electrophoresis and
      Southern blotting. RESULTS: Plasma Lp(a) was significantly higher in patients.
      The mean kringle number for the smallest isoform was also lower in patients than
      in controls, but no differences were found in the distribution of the largest
      isoform. All patients and controls were heterozygotes. During storage, mean Lp(a)
      decreased significantly in samples from patients (-23%; P <0.001) but not in
      samples from controls (-9%; P, not significant). This was not related to the
      kringle number and was limited to samples with initial plasma Lp(a)
      concentrations between 41 and 345 mg/L. CONCLUSIONS: Plasma Lp(a) from patients
      is less stable than Lp(a) from controls, and the difference is not related to
      distribution of apo(a) genotypes but may be concentration-dependent. Differential
      sample stability may complicate the interpretation of several studies.

PMID- 11514403
TI  - Whole-blood calcineurin activity is not predicted by cyclosporine blood
      concentration in renal transplant recipients.
AB  - BACKGROUND: In transplant patients, current cyclosporine (CsA) dose monitoring
      with classic pharmacokinetics has demonstrated limitations. Evaluation of the
      activity of calcineurin (CN), the serine-threonine phosphatase enzyme target of
      CsA, has been proposed as a reliable way to optimize CsA dosing. METHODS: CN
      activity was measured in whole blood in an attempt to overcome the high
      variability of results obtained previously with peripheral blood mononuclear
      cells (PBMCs). We also explored, in vitro, a possible relationship between the
      CsA concentration and CN inhibition in whole blood. Finally, we assessed whether
      the CsA blood trough concentration correlates with whole-blood CN activity in
      kidney transplant recipients (n = 15) on maintenance immunosuppression with CsA.
      RESULTS: In 14 healthy individuals, less scattered CN activity values were
      documented in whole blood than in the PBMC fraction. Whole-blood CN activity was
      higher than the sum of the enzyme activity in each cell blood fraction. After ex
      vivo incubation of whole blood from healthy subjects (n = 5) with increasing
      concentrations of CsA (50-1000 microg/L for 1 h), a concentration-dependent
      inhibition of CN activity was found comparable to that in the PBMC fraction.
      Moreover, in 15 kidney transplant recipients, no relationship was found between
      CsA pharmacokinetic parameters and CN activity at time 0. However, a highly
      significant correlation was found between CN area under the CN activity-time
      curve, which represents the extent of the CN daily inhibition, and CN activity at
      time 0 (r = 0.79; P <0.01) and at 12 h postdosing (r = 0.96; P <0.01).
      CONCLUSIONS: Measuring CN activity in whole-blood samples is a reproducible
      method. In kidney transplant recipients, CsA trough concentrations do not predict
      baseline CN activity. Moreover, a single CN activity monitoring at baseline or at
      time 12 h post-CsA dosing may be a useful surrogate for the inhibition of this
      enzyme by CsA during 12 h.

PMID- 11514405
TI  - Multivariate discriminant function based on six biochemical markers in blood can
      predict the cirrhotic evolution of chronic hepatitis.
AB  - BACKGROUND: Serologic markers have been proposed for monitoring hepatic fibrosis
      in chronic active liver disease. Because none of these markers, when used singly,
      is totally satisfactory, we developed and evaluated a multivariate approach.
      METHODS: We studied two cohorts of chronic hepatitis (54 patients) and cirrhosis
      patients (49 patients) to identify a panel of biochemical markers that
      discriminates between the two diseases. Using multivariate discriminant analysis,
      we selected a function, based on the concentrations of six biochemical markers
      (fibronectin, prothrombin, pseudocholinesterase, alanine aminotransferase,
      manganese superoxide dismutase, and N-acetyl-beta-glucosaminidase). We then
      prospectively validated this function on a second temporal cohort of patients.
      RESULTS: Multivariate discriminant analysis correctly classified 93.7% of
      patients (94.3% of chronic hepatitis and 92.9% of cirrhosis patients) in the
      first cohort and 85% of patients (89.5% of chronic hepatitis patients and 81% of
      cirrhosis patients) in the second cohort. CONCLUSIONS: Discriminant analysis of
      results of six inexpensive biochemical markers provides a high predictive value
      for differentiation between liver cirrhosis and chronic hepatitis. Consequently,
      these biochemical markers condensed into a multivariate discriminant analysis
      value for each patient provide information that can be contributory for
      subsequent options during the evolution of the natural history of chronic
      hepatitis.

PMID- 11514406
TI  - PCR on cell lysates obtained from whole blood circumvents DNA isolation.

PMID- 11514404
TI  - Nitrogen metabolism and bone metabolism markers in healthy adults during 16 weeks
      of bed rest.
AB  - BACKGROUND: The associations between nitrogen metabolism and bone turnover during
      bed rest are still not completely understood. METHODS: We measured nitrogen
      balance (nitrogen intake minus urinary nitrogen excretion) and biochemical
      metabolic markers of calcium and bone turnover in six males before head-down tilt
      bed rest (baseline), during 2, 10, and 14 weeks of immobilization, and after
      reambulation. RESULTS: The changes in nitrogen balance were highest between
      baseline and week 2 (net change, -5.05 +/- 1.30 g/day; 3.6 +/- 0.6 g/day at
      baseline vs -1.45 +/- 1.3 g/day at week 2; P<0.05). In parallel, serum intact
      osteocalcin (a marker of bone formation) was already reduced and renal calcium
      and phosphorus excretions were increased at week 2 (P <0.05). Fasting serum
      calcium and phosphorus values and renal excretion of N-telopeptide (a bone
      resorption marker) were enhanced at weeks 10 and 14 (P <0.05-0.001), whereas
      serum concentrations of parathyroid hormone, calcitriol, and type I collagen
      propeptide (a marker of bone collagen formation) were decreased at week 14 (P
      <0.05-0.01). Significant associations were present between changes of serum
      intact osteocalcin and 24-h calcium excretion (P <0.001), nitrogen balance and 24
      h phosphorus excretion (P <0.001), nitrogen balance and renal N-telopeptide
      excretion (P <0.05), and between serum osteocalcin and nitrogen balance (P
      <0.025). CONCLUSIONS: Bone formation decreases rapidly during immobilization in
      parallel with a higher renal excretion of intestinally absorbed calcium. These
      changes appear in association with the onset of a negative nitrogen balance, but
      decreased bone collagen synthesis and enhanced collagen breakdown occur after a
      time lag of several weeks.

PMID- 11514407
TI  - Anodic stripping voltammetry compared with graphite furnace atomic absorption
      spectrophotometry for blood lead analysis.

PMID- 11514408
TI  - Compatibility of the Abbott IMx homocysteine assay with citrate-anticoagulated
      plasma and stability of homocysteine in citrated whole blood.

PMID- 11514409
TI  - Serum C-reactive protein in Canadian Inuit and its association with genetic
      variation on chromosome 1q21.

PMID- 11514410
TI  - Analytical performance of specific-protein assays on the Abbott Aeroset system.

PMID- 11514411
TI  - Lead poisoning: a new biochemical perspective on the differentiation between
      acquired and hereditary neuroporphyria.

PMID- 11514412
TI  - Stability of ketamine and its metabolites norketamine and dehydronorketamine in
      human biological samples.

PMID- 11514413
TI  - Diurnal variation of human chorionic gonadotropin beta-core fragment
      concentrations in urine during second trimester of pregnancy.

PMID- 11514414
TI  - Protein fragments in urine have been considerably underestimated by various
      protein assays.

PMID- 11514415
TI  - Integration of olanzapine determinations in a HPLC-diode array detection system
      for routine psychotropic drug monitoring.

PMID- 11514416
TI  - Diurnal variations in serum and urine markers of type I and type III collagen
      turnover in children.

PMID- 11514417
TI  - Diagnostic accuracies for celiac disease of four tissue transglutaminase
      autoantibody tests using human antigen.

PMID- 11514418
TI  - Determination of malondialdehyde as dithiobarbituric acid adduct in biological
      samples by HPLC with fluorescence detection: comparison with ultraviolet-visible
      spectrophotometry.

PMID- 11514419
TI  - Real-time PCR assay with fluorescent hybridization probes for exact and rapid
      genotyping of the angiotensin-converting enzyme gene insertion/deletion
      polymorphism.

PMID- 11514420
TI  - Detection of anti-survivin antibody in gastrointestinal cancer patients.

PMID- 11514421
TI  - EDTA samples are stable for prothrombin time measurement by combined
      thromboplastin reagent.

PMID- 11514422
TI  - Creatine kinase isoenzyme MB (CKMB) controversy: perimortal tissue acidosis may
      explain the absence of CKMB in myocardium at autopsy.

PMID- 11514423
TI  - Between-assay differences in serum growth hormone (GH) measurements: importance
      in the diagnosis of GH deficiency in childhood.

PMID- 11514424
TI  - Plasma total homocysteine in hyper- and hypothyroid patients before and during 12
      months of treatment.

PMID- 11514425
TI  - Loop-mediated isothermal amplification reaction using a nondenatured template.

PMID- 11514426
TI  - High-sensitivity C-reactive protein: product claims and the Food and Drug
      Administration.

PMID- 11514428
TI  - Re: Europium nanoparticles and time-resolved fluorescence for ultrasensitive
      detection of prostate-specific antigen.

PMID- 11514429
TI  - Is RNA in serum bound to nucleoprotein complexes?

PMID- 11514434
TI  - Plant breeding giants. Burbank, the artist; Vavilov, the scientist.

PMID- 11514435
TI  - Coordination between fission yeast glucan formation and growth requires a
      sphingolipase activity.
AB  - css1 mutants display a novel defect in Schizosaccharomyces pombe cell wall
      formation. The mutant cells are temperature-sensitive and accumulate large
      deposits of material that stain with calcofluor and aniline blue in their
      periplasmic space. Biochemical analyses of this material indicate that it
      consists of alpha- and beta-glucans in the same ratio as found in cell walls of
      wild-type S. pombe. Strikingly, the glucan deposits in css1 mutant cells do not
      affect their overall morphology. The cells remain rod shaped, and the thickness
      of their walls is unaltered. Css1p is an essential protein related to mammalian
      neutral sphingomyelinase and is responsible for the inositolphosphosphingolipid
      phospholipase C activity observed in S. pombe membranes. Furthermore, expression
      of css1(+) can compensate for loss of ISC1, the enzyme responsible for this
      activity in Saccharomyces cerevisiae membranes. Css1p localizes to the entire
      plasma membrane and secretory pathway; a C-terminal fragment of Css1p, predicted
      to encode a single membrane-spanning segment, is sufficient to direct membrane
      localization of the heterologous protein, GFP. Our results predict the existence
      of an enzyme(s) or process(es) essential for the coordination of S. pombe cell
      wall formation and division that is, in turn, regulated by a sphingolipid
      metabolite.

PMID- 11514436
TI  - Correct regulation of the septation initiation network in Schizosaccharomyces
      pombe requires the activities of par1 and par2.
AB  - In Schizosaccharomyces pombe, the initiation of cytokinesis is regulated by a
      septation initiation network (SIN). We previously reported that deletion of par1
      and par2, two S. pombe genes encoding B' regulatory subunits of protein
      phosphatase 2A, causes a multiseptation phenotype, very similar to that seen in
      hyperactive SIN mutants. In this study, we examined the genetic interactions
      between par deletions and mutations in the genes encoding components of SIN and
      found that deletion of par1 and par2 suppressed the morphological and viability
      defects caused by overproduction of Byr4p and rescued a loss-of-function allele
      of spg1. However, par deletions could not suppress any mutations in genes
      downstream of spg1 in the SIN pathway. We showed further that, in suppressing the
      lethality of a spg1 loss-of-function allele, the correct localization of Cdc7p to
      the spindle pole body (SPB), which is normally lost in spg1 mutant cells, was
      restored. The fact that par mutant cells themselves exhibited a symmetric
      localization of Cdc7p to SPBs indicated a hyperactivity of SIN in such cells. On
      the basis of our epistasis analyses and cytological studies, we concluded that
      par genes normally negatively regulate SIN at or upstream of cdc7, ensuring that
      multiple rounds of septation do not occur.

PMID- 11514437
TI  - SPO14 separation-of-function mutations define unique roles for phospholipase D in
      secretion and cellular differentiation in Saccharomyces cerevisiae.
AB  - In Saccharomyces cerevisiae, phospholipase D (PLD), encoded by the SPO14 gene,
      catalyzes the hydrolysis of phosphatidylcholine, producing choline and
      phosphatidic acid. SPO14 is essential for cellular differentiation during meiosis
      and is required for Golgi function when the normal secretory apparatus is
      perturbed (Sec14-independent secretion). We isolated specific alleles of SPO14
      that support Sec14-independent secretion but not sporulation. Identification of
      these separation-of-function alleles indicates that the role of PLD in these two
      physiological processes is distinct. Analyses of the mutants reveal that the
      corresponding proteins are stable, phosphorylated, catalytically active in vitro,
      and can localize properly within the cell during meiosis. Surprisingly, the
      separation-of-function mutations map to the conserved catalytic region of the PLD
      protein. Choline and phosphatidic acid molecular species profiles during Sec14
      independent secretion and meiosis reveal that while strains harboring one of
      these alleles, spo14S-11, hydrolyze phosphatidylcholine in Sec14-independent
      secretion, they fail to do so during sporulation or normal vegetative growth.
      These results demonstrate that Spo14 PLD catalytic activity and cellular function
      can be differentially regulated at the level of phosphatidylcholine hydrolysis.

PMID- 11514438
TI  - The yeast cytoplasmic LsmI/Pat1p complex protects mRNA 3' termini from partial
      degradation.
AB  - A key aspect of understanding eukaryotic gene regulation will be the
      identification and analysis of proteins that bind mRNAs and control their
      function. Recently, a complex of seven Lsm proteins and the Pat1p have been shown
      to interact with yeast mRNAs and promote mRNA decapping. In this study we present
      several observations to indicate that the LsmI/Pat1 complex has a second distinct
      function in protecting the 3'-UTR of mRNAs from trimming. First, mutations in the
      LSM1 to LSM7, as well as PAT1, genes led to the accumulation of MFA2pG and PGK1pG
      transcripts that had been shortened by 10-20 nucleotides at their 3' ends
      (referred to as trimming). Second, the trimming of these mRNAs was more severe at
      the high temperature, correlating with the inability of these mutant strains to
      grow at high temperature. In contrast, trimming did not occur in a dcp1 Delta
      strain, wherein the decapping enzyme is lacking. This indicates that trimming is
      not simply a consequence of the inhibition of mRNA decapping. Third, the
      temperature-sensitive growth of lsm and pat1 mutants was suppressed by mutations
      in the exosome or the functionally related Ski proteins, which are required for
      efficient 3' to 5' mRNA degradation of mRNA. Moreover, in lsm ski double mutants,
      higher levels of the trimmed mRNAs accumulated, indicating that exosome function
      is not required for mRNA trimming but that the exosome does degrade the trimmed
      mRNAs. These results raise the possibility that the temperature-sensitive growth
      of the lsm1-7 and pat1 mutants is at least partially due to mRNA trimming, which
      either inactivates the function of the mRNAs or makes them available for
      premature 3' to 5' degradation by the exosome.

PMID- 11514439
TI  - Meiotic recombination involving heterozygous large insertions in Saccharomyces
      cerevisiae: formation and repair of large, unpaired DNA loops.
AB  - Meiotic recombination in Saccharomyces cerevisiae involves the formation of
      heteroduplexes, duplexes containing DNA strands derived from two different
      homologues. If the two strands of DNA differ by an insertion or deletion, the
      heteroduplex will contain an unpaired DNA loop. We found that unpaired loops as
      large as 5.6 kb can be accommodated within a heteroduplex. Repair of these loops
      involved the nucleotide excision repair (NER) enzymes Rad1p and Rad10p and the
      mismatch repair (MMR) proteins Msh2p and Msh3p, but not several other NER (Rad2p
      and Rad14p) and MMR (Msh4p, Msh6p, Mlh1p, Pms1p, Mlh2p, Mlh3p) proteins.
      Heteroduplexes were also formed with DNA strands derived from alleles containing
      two different large insertions, creating a large "bubble"; repair of this
      substrate was dependent on Rad1p. Although meiotic recombination events in yeast
      are initiated by double-strand DNA breaks (DSBs), we showed that DSBs occurring
      within heterozygous insertions do not stimulate interhomologue recombination.

PMID- 11514440
TI  - eEF1A Controls ascospore differentiation through elevated accuracy, but controls
      longevity and fruiting body formation through another mechanism in Podospora
      anserina.
AB  - Antisuppressor mutations in the eEF1A gene of Podospora anserina were previously
      shown to impair ascospore formation, to drastically increase life span, and to
      permit the development of the Crippled Growth degenerative process. Here, we show
      that eEF1A controls ascospore formation through accuracy level maintenance.
      Examination of antisuppressor mutant perithecia reveals two main cytological
      defects, mislocalization of spindle and nuclei and nuclear death. Antisuppression
      levels are shown to be highly dependent upon both the mutation site and the
      suppressor used, precluding any correlation between antisuppression efficiency
      and severity of the sporulation impairment. Nevertheless, severity of ascospore
      differentiation defect is correlated with resistance to paromomycin. We also show
      that eEF1A controls fruiting body formation and longevity through a mechanism(s)
      different from accuracy control. In vivo, GFP tagging of the protein in a way
      that partly retains its function confirmed earlier cytological observation; i.e.,
      this factor is mainly diffuse within the cytosol, but may transiently accumulate
      within nuclei or in defined regions of the cytoplasm. These data emphasize the
      fact that the translation apparatus exerts a global regulatory control over cell
      physiology and that eEF1A is one of the key factors involved in this monitoring.

PMID- 11514441
TI  - Changes in mate recognition through alterations of pheromones and receptors in
      the multisexual mushroom fungus Schizophyllum commune.
AB  - Schizophyllum commune has thousands of mating types defined in part by numerous
      lipopeptide pheromones and their G-protein-coupled receptors. These molecules are
      encoded within multiple versions of two redundantly functioning B mating-type
      loci, B alpha and B beta. Compatible combinations of pheromones and receptors,
      produced by individuals of different B mating types, trigger a pathway of
      fertilization required for sexual development. Analysis of the B beta 2 mating
      type locus revealed a large cluster of genes encoding a single pheromone receptor
      and eight different pheromones. Phenotypic effects of mutations within these
      genes indicated that small changes in both types of molecules could significantly
      alter their specificity of interaction. For example, a conservative amino acid
      substitution in a pheromone resulted in a gain of function toward one receptor
      and a loss of function with another. A two-amino-acid deletion from a receptor
      precluded the mutant pheromone from activating the mutant receptor, yet this
      receptor was activated by other pheromones. Sequence comparisons provided clues
      toward understanding how so many variants of these multigenic loci could have
      evolved through duplication and mutational divergence. A three-step model for the
      origin of new variants comparable to those found in nature is presented.

PMID- 11514442
TI  - Strong diversifying selection on domains of the Plasmodium falciparum apical
      membrane antigen 1 gene.
AB  - The surface-accessible ectodomain region of the Plasmodium falciparum apical
      membrane antigen 1 (AMA1) is a malaria vaccine candidate. The amino acid sequence
      may be under selection from naturally acquired immune responses, and previous
      analyses with a small number of allele sequences indicate a non-neutral pattern
      of nucleotide variation. To investigate whether there is selection to maintain
      polymorphism within a population, and to identify the parts of the ectodomain
      under strongest selection, a sample of 51 alleles from a single endemic
      population was studied. Analyses using Fu and Li's D and F tests, Tajima's D
      test, and the McDonald-Kreitman test (with the chimpanzee parasite P. reichenowi
      as outgroup) show significant departure from neutrality and indicate the
      selective maintenance of alleles within the population. There is also evidence of
      a very high recombination rate throughout the sequence, as estimated by the
      recombination parameter, C, and by the rapid decline in linkage disequilibrium
      with increasing nucleotide distance. Of the three domains (I-III) encoding
      structures determined by disulfide bonds, the evidence of selection is strongest
      for Domains I and III. We predict that these domains in particular are targets of
      naturally acquired protective immune responses in humans.

PMID- 11514443
TI  - Specification of germ cell fates by FOG-3 has been conserved during nematode
      evolution.
AB  - Rapid changes in sexual traits are ubiquitous in evolution. To analyze this
      phenomenon, we are studying species of the genus Caenorhabditis. These animals
      use one of two different mating systems-male/hermaphroditic, like the model
      organism Caenorhabditis elegans, or male/female, like C. remanei. Since
      hermaphrodites are essentially females that produce sperm for self-fertilization,
      elucidating the control of cell fate in the germ line in each species could
      provide the key to understanding how these mating systems evolved. In C. elegans,
      FOG-3 is required to specify that germ cells become sperm. Thus, we cloned its
      homologs from both C. remanei and C. briggsae. Each species produces a single
      homolog of FOG-3, and RNA-mediated interference indicates that FOG-3 functions in
      each species to specify that germ cells develop as sperm rather than as oocytes.
      What factors account for the different mating systems? Northern analyses and RT
      PCR data reveal that the expression of fog-3 is always correlated with
      spermatogenesis. Since the promoters for all three fog-3 genes contain binding
      sites for the transcription factor TRA-1A and are capable of driving expression
      of fog-3 in C. elegans hermaphrodites, we propose that alterations in the
      upstream sex-determination pathway, perhaps acting through TRA-1A, allow
      spermatogenesis in C. elegans and C. briggsae XX larvae but not in C. remanei.

PMID- 11514444
TI  - Sex determination in the parasitic nematode Strongyloides ratti.
AB  - The parasitic nematode Strongyloides ratti reproduces by both parthenogenesis and
      sexual reproduction, but its genetics are poorly understood. Cytological evidence
      suggests that sex determination is an XX/XO system. To investigate this
      genetically, we isolated a number of sex-linked DNA markers. One of these
      markers, Sr-mvP1, was shown to be single copy and present at a higher dose in
      free-living females than in free-living males. The inheritance of two alleles of
      Sr-mvP1 by RFLP analysis was consistent with XX female and XO male genotypes.
      Analysis of the results of sexual reproduction demonstrated that all progeny
      inherit the single paternal X chromosome and one of the two maternal X
      chromosomes. Therefore, all stages of the S. ratti life cycle, with the exception
      of the free-living males, are XX and genetically female. These findings are
      considered in relation to previous analyses of S. ratti and to other known sex
      determination systems.

PMID- 11514445
TI  - The nonA gene in Drosophila conveys species-specific behavioral characteristics.
AB  - The molecular basis of species-specific differences in courtship behavior, a
      critical factor in preserving species boundaries, is poorly understood. Genetic
      analysis of all but the most closely related species is usually impossible, given
      the inviability of hybrids. We have therefore applied interspecific
      transformation of a single candidate behavioral locus, no-on-transient A (nonA),
      between Drosophila virilis and D. melanogaster, to investigate whether nonA, like
      the period gene, might encode species-specific behavioral information. Mutations
      in nonA can disrupt both visual behavior and the courtship song in D.
      melanogaster. The lovesong of nonA(diss) mutant males superficially resembles
      that of D. virilis, a species that diverged from D. melanogaster 40-60 mya.
      Transformation of the cloned D. virilis nonA gene into D. melanogaster hosts
      carrying a synthetic deletion of the nonA locus restored normal visual function
      (the phenotype most sensitive to nonA mutation). However, the courtship song of
      transformant males showed several features characteristic of the corresponding D.
      virilis signal, indicating that nonA can act as a reservoir for species-specific
      information. This candidate gene approach, together with interspecific
      transformation, can therefore provide a direct avenue to explore potential
      speciation genes in genetically and molecularly tractable organisms such as
      Drosophila.

PMID- 11514446
TI  - A genetic screen for suppressors and enhancers of the Drosophila PAN GU cell
      cycle kinase identifies cyclin B as a target.
AB  - The early cell cycles of Drosophila embryogenesis involve rapid oscillations
      between S phase and mitosis. These unique S-M cycles are driven by maternal
      stockpiles of components necessary for DNA replication and mitosis. Three genes,
      pan gu (png), plutonium (plu), and giant nuclei (gnu) are required to control the
      cell cycle specifically at the onset of Drosophila development by inhibiting DNA
      replication and promoting mitosis. PNG is a protein kinase that is in a complex
      with PLU. We employed a sensitized png mutant phenotype to screen for genes that
      when reduced in dosage would dominantly suppress or enhance png. We screened
      deficiencies covering over 50% of the autosomes and identified both enhancers and
      suppressors. Mutations in eIF-5A and PP1 87B dominantly suppress png. Cyclin B
      was shown to be a key PNG target. Mutations in cyclin B dominantly enhance png,
      whereas png is suppressed by cyclin B overexpression. Suppression occurs via
      restoration of Cyclin B protein levels that are decreased in png mutants. The plu
      and gnu phenotypes are also suppressed by cyclin B overexpression. These studies
      demonstrate that a crucial function of PNG in controlling the cell cycle is to
      permit the accumulation of adequate levels of Cyclin B protein.

PMID- 11514447
TI  - Dynamics of R1 and R2 elements in the rDNA locus of Drosophila simulans.
AB  - The mobile elements R1 and R2 insert specifically into the rRNA gene locus (rDNA
      locus) of arthropods, a locus known to undergo concerted evolution, the
      recombinational processes that preserve the sequence homogeneity of all repeats.
      To monitor how rapidly individual R1 and R2 insertions are turned over in the
      rDNA locus by these processes, we have taken advantage of the many 5' truncation
      variants that are generated during the target-primed reverse transcription
      mechanism used by these non-LTR retrotransposons for their integration. A simple
      PCR assay was designed to reveal the pattern of the 5' variants present in the
      rDNA loci of individual X chromosomes in a population of Drosophila simulans.
      Each rDNA locus in this population was found to have a large, unique collection
      of 5' variants. Each variant was present at low copy number, usually one copy per
      chromosome, and was seldom distributed to other chromosomes in the population.
      The failure of these variants to spread to other units in the same rDNA locus
      suggests a strong recombinational bias against R1 and R2 that results in the
      individual copies of these elements being rapidly lost from the rDNA locus. This
      bias suggests a significantly higher frequency of R1 and R2 retrotransposition
      than we have previously suggested.

PMID- 11514448
TI  - Molecular genetic dissection of the sex-specific and vital functions of the
      Drosophila melanogaster sex determination gene fruitless.
AB  - A multibranched hierarchy of regulatory genes controls all aspects of somatic
      sexual development in Drosophila melanogaster. One branch of this hierarchy is
      headed by the fruitless (fru) gene and functions in the central nervous system,
      where it is necessary for male courtship behavior as well as the differentiation
      of a male-specific abdominal structure, the muscle of Lawrence (MOL). A
      preliminary investigation of several of the mutations described here showed that
      the fru gene also has a sex-nonspecific vital function. The fru gene produces a
      complex set of transcripts through the use of four promoters and alternative
      splicing. Only the primary transcripts produced from the most distal (P1)
      promoter are sex-specifically spliced under direction of the sex-determination
      hierarchy. We have analyzed eight new fru mutations, created by X-ray mutagenesis
      and P-element excision, to try to gain insight into the relationship of specific
      transcript classes to specific fru functions. Males that lack the P1-derived fru
      transcripts show a complete absence of sexual behavior, but no other defects
      besides the loss of the MOL. Both males and females that have reduced levels of
      transcripts from the P3 promoter develop into adults but frequently die after
      failing to eclose. Analysis of the morphology and behavior of adult escapers
      showed that P3-encoded functions are required for the proper differentiation and
      eversion of imaginal discs. Furthermore, the reduction in the size of the
      neuromuscular junctions on abdominal muscles in these animals suggests that one
      of fru's sex-nonspecific functions involves general aspects of neuronal
      differentiation. In mutants that lack all fru transcripts as well as a small
      number of adjacent genes, animals die at an early pupal stage, indicating that
      fru's function is required only during late development. Thus, fru functions both
      in the sex-determination regulatory hierarchy to control male sexual behavior
      through sex-specific transcripts and sex-nonspecifically to control the
      development of imaginal discs and motorneuronal synapses during adult development
      through sex-nonspecific transcript classes.

PMID- 11514449
TI  - Map position and expression of the genes in the 38 region of Drosophila.
AB  - With the completion of the Drosophila genome sequence, an important next step is
      to extract its biological information by systematic functional analysis of genes.
      We have produced a high-resolution genetic map of cytological region 38 of
      Drosophila using 41 deficiency stocks that provide a total of 54 breakpoints
      within the region. Of a total of 45 independent P-element lines that mapped by in
      situ hybridization to the region, 14 targeted 7 complementation groups within the
      38 region. Additional EMS, X-ray, and spontaneous mutations define a total of 17
      complementation groups. Because these two pools partially overlap, the completed
      analysis revealed 21 distinct complementation groups defined by point mutations.
      Seven additional functions were defined by trans-heterozygous combinations of
      deficiencies, resulting in a total of 28 distinct functions. We further produced
      a developmental expression profile for the 760 kb from 38B to 38E. Of 135
      transcription units predicted by GENSCAN, 22 have at least partial homology to
      mobile genetic elements such as transposons and retroviruses and 17 correspond to
      previously characterized genes. We analyzed the developmental expression pattern
      of the remaining genes using poly(A)(+) RNA from ovaries, early and late embryos,
      larvae, males, and females. We discuss the correlation between GENSCAN
      predictions and experimentally confirmed transcription units, the high number of
      male-specific transcripts, and the alignment of the genetic and physical maps in
      cytological region 38.

PMID- 11514450
TI  - The activation of a neocentromere in Drosophila requires proximity to an
      endogenous centromere.
AB  - The centromere is essential for proper segregation and inheritance of genetic
      information. Centromeres are generally regulated to occur exactly once per
      chromosome; failure to do so leads to chromosome loss or damage and loss of
      linked genetic material. The mechanism for faithful regulation of centromere
      activity and number is unknown. The presence of ectopic centromeres
      (neocentromeres) has allowed us to probe the requirements and characteristics of
      centromere activation, maintenance, and structure. We utilized chromosome
      derivatives that placed a 290-kilobase "test segment" in three different contexts
      within the Drosophila melanogaster genome--immediately adjacent to (1)
      centromeric chromatin, (2) centric heterochromatin, or (3) euchromatin. Using
      irradiation mutagenesis, we freed this test segment from the source chromosome
      and genetically assayed whether the liberated "test fragment" exhibited
      centromere activity. We observed that this test fragment behaved differently with
      respect to centromere activity when liberated from different chromosomal
      contexts, despite an apparent sequence identity. Test segments juxtaposed to an
      active centromere produced fragments with neocentromere activity, whereas test
      segments far from centromeres did not. Once established, neocentromere activity
      was stable. The imposition of neocentromere activity on juxtaposed DNA supports
      the hypothesis that centromere activity and identity is capable of spreading and
      is regulated epigenetically.

PMID- 11514451
TI  - The cyclope gene of Drosophila encodes a cytochrome c oxidase subunit VIc
      homolog.
AB  - Cytochrome c oxidase is the terminal enzyme of the mitochondrial electron
      transfer chain. In eukaryotes, the enzyme is composed of 3 mitochondrial DNA
      encoded subunits and 7-10 (in mammals) nuclear DNA-encoded subunits. This enzyme
      has been extensively studied in mammals and yeast but, in Drosophila, very little
      is known and no mutant has been described so far. Here we report the genetic and
      molecular characterization of mutations in cyclope (cype) and the cloning of the
      gene encoding a cytochrome c oxidase subunit VIc homolog. cype is an essential
      gene whose mutations are lethal and show pleiotropic phenotypes. The 77-amino
      acid peptide encoded by cype is 46% identical and 59% similar to the human
      subunit (75 amino acids). The transcripts are expressed maternally and throughout
      development in localized regions. They are found predominantly in the central
      nervous system of the embryo; in the central region of imaginal discs; in the
      germarium, follicular, and nurse cells of the ovary; and in testis. A search in
      the Genome Annotation Database of Drosophila revealed the absence of subunit VIIb
      and the presence of 9 putative nuclear cytochrome c oxidase subunits with high
      identity scores when compared to the 10 human subunits.

PMID- 11514452
TI  - Isolation and characterization of the Xanthine dehydrogenase gene of the
      Mediterranean fruit fly, Ceratitis capitata.
AB  - Xanthine dehydrogenase (XDH) is a member of the molybdenum hydroxylase family of
      enzymes catalyzing the oxidation of hypoxanthine and xanthine to uric acid. The
      enzyme is also required for the production of one of the major Drosophila eye
      pigments, drosopterin. The XDH gene has been isolated in many species
      representing a broad cross section of the major groups of living organisms,
      including the cDNA encoding XDH from the Mediterranean fruit fly Ceratitis
      capitata (CcXDH) described here. CcXDH is closely related to other insect XDHs
      and is able to rescue the phenotype of the Drosophila melanogaster XDH mutant,
      rosy, in germline transformation experiments. A previously identified medfly
      mutant, termed rosy, whose phenotype is suggestive of a disruption in XDH
      function, has been examined for possible mutations in the XDH gene. However, we
      find no direct evidence that a mutation in the CcXDH gene or that a reduction in
      the CcXDH enzyme activity is present in rosy medflies. Conclusive studies of the
      nature of the medfly rosy mutant will require rescue by germline transformation
      of mutant medflies.

PMID- 11514453
TI  - Excess of rare amino acid polymorphisms in the Toll-like receptor 4 in humans.
AB  - The Toll-like receptor 4 protein acts as the transducing subunit of the
      lipopolysaccharide receptor complex and assists in the detection of Gram-negative
      pathogens within the mammalian host. Several lines of evidence support the view
      that variation at the TLR4 locus may alter host susceptibility to Gram-negative
      infection or the outcome of infection. Here, we surveyed TLR4 sequence variation
      in the complete coding region (2.4 kb) in 348 individuals from several population
      samples; in addition, a subset of the individuals was surveyed at 1.1 kb of
      intronic sequence. More than 90% of the chromosomes examined encoded the same
      structural isoform of TLR4, while the rest harbored 12 rare amino acid variants.
      Conversely, the variants at silent sites (intronic and synonymous positions)
      occur at both low and high frequencies and are consistent with a neutral model of
      mutation and random drift. The spectrum of allele frequencies for amino acid
      variants shows a significant skew toward lower frequencies relative to both the
      neutral model and the pattern observed at linked silent sites. This is consistent
      with the hypothesis that weak purifying selection acted on TLR4 and that most
      mutations affecting TLR4 protein structure have at least mildly deleterious
      phenotypic effects. These results may imply that genetic variants contributing to
      disease susceptibility occur at low frequencies in the population and suggest
      strategies for optimizing the design of disease-mapping studies.

PMID- 11514455
TI  - C57BL/6J-T-associated sex reversal in mice is caused by reduced expression of a
      Mus domesticus Sry allele.
AB  - C57BL/6J-T-associated sex reversal (B6-TAS) in XY mice results in ovarian
      development and involves (1) hemizygosity for Tas, a gene located in the region
      of Chromosome 17 deleted in T(hp) and T(Orl), (2) homozygosity for one or more B6
      derived autosomal genes, and (3) the presence of the AKR Y chromosome. Here we
      report results from experiments designed to investigate the Y chromosome
      component of this sex reversal. Testis development was restored in B6 T(Orl)/+
      XY(AKR) mice carrying a Mus musculus Sry transgene. In addition, two functionally
      different classes of M. domesticus Sry alleles were identified among eight
      standard and two wild-derived inbred strains. One class, which includes AKR, did
      not initiate normal testis development in B6 T(Orl)/+ XY mice, whereas the other
      did. DNA sequence analysis of the Sry ORF and a 5' 800-bp segment divided these
      inbred strains into the same groups. Finally, we found that Sry is transcribed in
      B6 T(Orl)/+ XY(AKR) fetal gonads but at a reduced level. These results pinpoint
      Sry as the Y-linked component of B6-TAS. We hypothesize that the inability of
      specific M. domesticus Sry alleles to initiate normal testis development in B6
      T(Orl)/+ XY(AKR) mice results from a biologically insufficient level of Sry
      expression, allowing the ovarian development pathway to proceed.

PMID- 11514454
TI  - Capture of DNA sequences at double-strand breaks in mammalian chromosomes.
AB  - To study double-strand break (DSB)-induced mutations in mammalian chromosomes, we
      transfected thymidine kinase (tk)-deficient mouse fibroblasts with a DNA
      substrate containing a recognition site for yeast endonuclease I-SceI embedded
      within a functional tk gene. To introduce a genomic DSB, cells were
      electroporated with a plasmid expressing endonuclease I-SceI, and clones that had
      lost tk function were selected. Among 253 clones analyzed, 78% displayed small
      deletions or insertions of several nucleotides at the DSB site. Surprisingly,
      approximately 8% of recovered mutations involved the capture of one or more DNA
      fragments. Among 21 clones that had captured DNA, 10 harbored a specific segment
      of the I-SceI expression plasmid mapping between two replication origins on the
      plasmid. Four clones had captured a long terminal repeat sequence from an
      intracisternal A particle (an endogenous retrovirus-like sequence) and one had
      captured what appears to be a cDNA copy of a moderately repetitive B2 sequence.
      Additional clones displayed segments of the tk gene and/or microsatellite
      sequences copied into the DSB. This first systematic study of DNA capture at DSBs
      in a mammalian genome suggests that DSB repair may play a considerable role in
      the evolution of eukaryotic genomes.

PMID- 11514456
TI  - Molecular and phenotypic analysis of Attractin mutant mice.
AB  - Mutations of the mouse Attractin (Atrn; formerly mahogany) gene were originally
      recognized because they suppress Agouti pigment type switching. More recently,
      effects independent of Agouti have been recognized: mice homozygous for the
      Atrn(mg-3J) allele are resistant to diet-induced obesity and also develop
      abnormal myelination and vacuolation in the central nervous system. To better
      understand the pathophysiology and relationship of these pleiotropic effects, we
      further characterized the molecular abnormalities responsible for two additional
      Atrn alleles, Atrn(mg) and Atrn(mg-L), and examined in parallel the phenotypes of
      homozygous and compound heterozygous animals. We find that the three alleles have
      similar effects on pigmentation and neurodegeneration, with a relative severity
      of Atrn(mg-3J) > Atrn(mg) > Atrn(mg-L), which also corresponds to the effects of
      the three alleles on levels of normal Atrn mRNA. Animals homozygous for Atrn(mg
      3J) or Atrn(mg), but not Atrn(mg-L), show reduced body weight, reduced adiposity,
      and increased locomotor activity, all in the presence of normal food intake.
      These results confirm that the mechanism responsible for the neuropathological
      alteration is a loss--rather than gain--of function, indicate that abnormal body
      weight in Atrn mutant mice is caused by a central process leading to increased
      energy expenditure, and demonstrate that pigmentation is more sensitive to levels
      of Atrn mRNA than are nonpigmentary phenotypes.

PMID- 11514457
TI  - Bacterial artificial chromosome-based physical map of the rice genome constructed
      by restriction fingerprint analysis.
AB  - Genome-wide physical mapping with bacteria-based large-insert clones (e.g., BACs,
      PACs, and PBCs) promises to revolutionize genomics of large, complex genomes. To
      accelerate rice and other grass species genome research, we developed a genome
      wide BAC-based map of the rice genome. The map consists of 298 BAC contigs and
      covers 419 Mb of the 430-Mb rice genome. Subsequent analysis indicated that the
      contigs constituting the map are accurate and reliable. Particularly important to
      proficiency were (1) a high-resolution, high-throughput DNA sequencing gel-based
      electrophoretic method for BAC fingerprinting, (2) the use of several
      complementary large-insert BAC libraries, and (3) computer-aided contig assembly.
      It has been demonstrated that the fingerprinting method is not significantly
      influenced by repeated sequences, genome size, and genome complexity. Use of
      several complementary libraries developed with different restriction enzymes
      minimized the "gaps" in the physical map. In contrast to previous estimates, a
      clonal coverage of 6.0-8.0 genome equivalents seems to be sufficient for
      development of a genome-wide physical map of approximately 95% genome coverage.
      This study indicates that genome-wide BAC-based physical maps can be developed
      quickly and economically for a variety of plant and animal species by restriction
      fingerprint analysis via DNA sequencing gel-based electrophoresis.

PMID- 11514458
TI  - Species and recombination effects on DNA variability in the tomato genus.
AB  - Population genetics theory predicts that strong selection for rare, beneficial
      mutations or against frequent, deleterious mutations reduces polymorphism at
      linked neutral (or weakly selected) sites. The reduction of genetic variation is
      expected to be more severe when recombination rates are lower. In outbreeding
      species, low recombination rates are usually confined to certain chromosomal
      regions, such as centromeres and telomeres. In contrast, in predominantly selfing
      species, the rarity of double heterozygotes leads to a reduced effective
      recombination rate in the whole genome. We investigated the effects of restricted
      recombination on DNA polymorphism in these two cases, analyzing five Lycopersicon
      species with contrasting mating systems: L. chilense, L. hirsutum, L. peruvianum,
      L. chmielewskii, and L. pimpinellifolium, of which only the first three species
      have self-incompatibility alleles. In each species, we determined DNA sequence
      variation of five single-copy genes located in chromosomal regions with either
      high or low recombination rate. We found that the mating system has a highly
      significant effect on the level of polymorphism, whereas recombination has only a
      weak influence. The effect of recombination on levels of polymorphism in
      Lycopersicon is much weaker than in other well-studied species, including
      Drosophila. To explain these observations, we discuss a number of hypotheses,
      invoking selection, recombination, and demographic factors associated with the
      mating system. We also provide evidence that L. peruvianum, showing a level of
      polymorphism (almost 3%) that is comparable to the level of divergence in the
      whole genus, is the ancestral species from which the other species of the genus
      Lycopersicon have originated relatively recently.

PMID- 11514459
TI  - Overdominant epistatic loci are the primary genetic basis of inbreeding
      depression and heterosis in rice. I. Biomass and grain yield.
AB  - To understand the genetic basis of inbreeding depression and heterosis in rice,
      main-effect and epistatic QTL associated with inbreeding depression and heterosis
      for grain yield and biomass in five related rice mapping populations were
      investigated using a complete RFLP linkage map of 182 markers, replicated
      phenotyping experiments, and the mixed model approach. The mapping populations
      included 254 F(10) recombinant inbred lines derived from a cross between Lemont
      (japonica) and Teqing (indica) and two BC and two testcross hybrid populations
      derived from crosses between the RILs and their parents plus two testers (Zhong
      413 and IR64). For both BY and GY, there was significant inbreeding depression
      detected in the RI population and a high level of heterosis in each of the BC and
      testcross hybrid populations. The mean performance of the BC or testcross hybrids
      was largely determined by their heterosis measurements. The hybrid breakdown
      (part of inbreeding depression) values of individual RILs were negatively
      associated with the heterosis measurements of their BC or testcross hybrids,
      indicating the partial genetic overlap of genes causing hybrid breakdown and
      heterosis in rice. A large number of epistatic QTL pairs and a few main-effect
      QTL were identified, which were responsible for >65% of the phenotypic variation
      of BY and GY in each of the populations with the former explaining a much greater
      portion of the variation. Two conclusions concerning the loci associated with
      inbreeding depression and heterosis in rice were reached from our results. First,
      most QTL associated with inbreeding depression and heterosis in rice appeared to
      be involved in epistasis. Second, most ( approximately 90%) QTL contributing to
      heterosis appeared to be overdominant. These observations tend to implicate
      epistasis and overdominance, rather than dominance, as the major genetic basis of
      heterosis in rice. The implications of our results in rice evolution and
      improvement are discussed.

PMID- 11514460
TI  - Overdominant epistatic loci are the primary genetic basis of inbreeding
      depression and heterosis in rice. II. Grain yield components.
AB  - The genetic basis underlying inbreeding depression and heterosis for three grain
      yield components of rice was investigated in five interrelated mapping
      populations using a complete RFLP linkage map, replicated phenotyping, and the
      mixed model approach. The populations included 254 F(10) recombinant inbred lines
      (RILs) derived from a cross between Lemont (japonica) and Teqing (indica), two
      backcross (BC) and two testcross populations derived from crosses between the
      RILs and the parents plus two testers (Zhong413 and IR64). For the yield
      components, the RILs showed significant inbreeding depression and hybrid
      breakdown, and the BC and testcross populations showed high levels of heterosis.
      The average performance of the BC or testcross hybrids was largely determined by
      heterosis. The inbreeding depression values of individual RILs were negatively
      associated with the heterosis measurements of the BC or testcross hybrids. We
      identified many epistatic QTL pairs and a few main-effect QTL responsible for
      >65% of the phenotypic variation of the yield components in each of the
      populations. Most epistasis occurred between complementary loci, suggesting that
      grain yield components were associated more with multilocus genotypes than with
      specific alleles at individual loci. Overdominance was also an important property
      of most loci associated with heterosis, particularly for panicles per plant and
      grains per panicle. Two independent groups of genes appeared to affect grain
      weight: one showing primarily nonadditive gene action explained 62.1% of the
      heterotic variation of the trait, and the other exhibiting only additive gene
      action accounted for 28.1% of the total trait variation of the F(1) mean values.
      We found no evidence suggesting that pseudo-overdominance from the repulsive
      linkage of completely or partially dominant QTL for yield components resulted in
      the overdominant QTL for grain yield. Pronounced overdominance resulting from
      epistasis expressed by multilocus genotypes appeared to explain the long-standing
      dilemma of how inbreeding depression could arise from overdominant genes.

PMID- 11514461
TI  - Five gametophytic mutations affecting pollen development and pollen tube growth
      in Arabidopsis thaliana.
AB  - Mutant analysis represents one of the most reliable approaches to identifying
      genes involved in plant development. The screening of the Versailles collection
      of Arabidopsis thaliana T-DNA insertion transformants has allowed us to isolate
      different mutations affecting male gametophytic functions and viability. Among
      several mutated lines, five have been extensively studied at the genetic,
      molecular, and cytological levels. For each mutant, several generations of
      selfing and outcrossing have been carried out, leading to the conclusion that all
      these mutations are tagged and affect only the male gametophyte. However, only
      one out of the five mutations is completely penetrant. A variable number of T-DNA
      copies has integrated in the mutant lines, although all segregate at one mutated
      locus. Two mutants could be defined as "early mutants": the mutated genes are
      presumably expressed during pollen grain maturation and their alteration leads to
      the production of nonfunctional pollen grains. Two other mutants could be defined
      as "late mutant" since their pollen is able to germinate but pollen tube growth
      is highly disturbed. Screening for segregation ratio distortions followed by
      thorough genetic analysis proved to be a powerful tool for identifying
      gametophytic mutations of all phases of pollen development.

PMID- 11514462
TI  - Modeling linkage disequilibrium between a polymorphic marker locus and a locus
      affecting complex dichotomous traits in natural populations.
AB  - Linkage disequilibrium is an important topic in evolutionary and population
      genetics. An issue yet to be settled is the theory required to extend the linkage
      disequilibrium analysis to complex traits. In this study, we present theoretical
      analysis and methods for detecting or estimating linkage disequilibrium (LD)
      between a polymorphic marker locus and any one of the loci affecting a complex
      dichotomous trait on the basis of samples randomly or selectively collected from
      natural populations. Statistical properties of these methods were investigated
      and their powers were compared analytically or by use of Monte Carlo simulations.
      The results show that the disequilibrium may be detected with a power of 80% by
      using phenotypic records and marker genotype when both the trait and marker
      variants are common (30%) and the LD is relatively high (40-100% of the
      theoretical maximum). The maximum-likelihood approach provides accurate estimates
      of the model parameters as well as detection of linkage disequilibrium. The
      likelihood method is preferred for its higher power and reliability in parameter
      estimation. The approaches developed in this article are also compared to those
      for analyzing a continuously distributed quantitative trait. It is shown that a
      larger sample size is required for the dichotomous trait model to obtain the same
      level of power in detecting linkage disequilibrium as the continuous trait
      analysis. Potential use of these estimates in mapping the trait locus is also
      discussed.

PMID- 11514463
TI  - The evolution of X-linked genomic imprinting.
AB  - We develop a quantitative genetic model to investigate the evolution of X
      imprinting. The model compares two forces that select for X-imprinting: genomic
      conflict caused by polygamy and sex-specific selection. Genomic conflict can only
      explain small reductions in maternal X gene expression and cannot explain
      silencing of the maternal X. In contrast, sex-specific selection can cause
      extreme differences in gene expression, in either direction (lowered maternal or
      paternal gene expression), even to the point of gene silencing of either the
      maternal or paternal copy. These conclusions assume that the Y chromosome lacks
      genetic activity. The presence of an active Y homologue makes imprinting resemble
      the autosomal pattern, with active paternal alleles (X- and Y-linked) and
      silenced maternal alleles. This outcome is likely to be restricted as Y-linked
      alleles are subject to the accumulation of deleterious mutations. Experimental
      evidence concerning X-imprinting in mouse and human is interpreted in the light
      of these predictions and is shown to be far more easily explained by sex-specific
      selection.

PMID- 11514464
TI  - Interpretation of variation across marker loci as evidence of selection.
AB  - Population structure and history have similar effects on the genetic diversity at
      all neutral loci. However, some marker loci may also have been strongly
      influenced by natural selection. Selection shapes genetic diversity in a locus
      specific manner. If we could identify those loci that have responded to selection
      during the divergence of populations, then we may obtain better estimates of the
      parameters of population history by excluding these loci. Previous attempts were
      made to identify outlier loci from the distribution of sample statistics under
      neutral models of population structure and history. Unfortunately these methods
      depend on assumptions about population structure and history that usually cannot
      be verified. In this article, we define new population-specific parameters of
      population divergence and construct sample statistics that are estimators of
      these parameters. We then use the joint distribution of these estimators to
      identify outlier loci that may be subject to selection. We found that outlier
      loci are easier to recognize when this joint distribution is conditioned on the
      total number of allelic states represented in the pooled sample at each locus.
      This is so because the conditional distribution is less sensitive to the values
      of nuisance parameters.

PMID- 11514465
TI  - Identification of a mutant locus by noncomplementation of a transposon insertion
      library in Saccharomyces cerevisiae.
AB  - We describe a new approach for identifying the gene corresponding to a mutation
      in Saccharomyces cerevisiae. A library of mTn-lacZ/LEU2 insertions is tested for
      failure to complement the mutation, and the noncomplementing insertion is used to
      obtain sequence. This approach offers an alternative to cloning by
      complementation with a plasmid library.

PMID- 11514466
TI  - Immediate angioplasty for the National Health Service?

PMID- 11514467
TI  - Stamps in cardiology: Conferences.

PMID- 11514468
TI  - The patient with acute myocardial infarction who does not receive reperfusion
      treatment.

PMID- 11514469
TI  - Eosinophilic aortitis and valvitis requiring aortic valve replacement.

PMID- 11514470
TI  - Electromagnetic interference in patients with implanted pacemakers or
      cardioverter-defibrillators.

PMID- 11514471
TI  - Getting Heart to developing countries.

PMID- 11514472
TI  - Atrial fibrillation coexisting with ventricular tachycardia: a challenge for dual
      chamber defibrillators.

PMID- 11514473
TI  - Peroxisome proliferator activated receptor gamma: a potential therapeutic target
      in the management of ischaemic heart disease.

PMID- 11514474
TI  - Glycoprotein IIb/IIIa inhibitors and acute coronary syndromes: summary report of
      the full submission to NICE, and beyond.

PMID- 11514475
TI  - Late acute thrombosis after paclitaxel eluting stent implantation.
AB  - Late (more than six months) total occlusion after coronary stenting is a
      progressive phenomenon occurring in approximately 4% of patients, leading to
      acute myocardial infarction in less than 0.5%. The process must be related to
      severe and progressive intimal hyperplasia. In patients receiving coronary
      stenting with simultaneous brachytherapy, late total occlusion has been reported
      at a higher rate and to be related to stent thrombosis rather than intimal
      hyperplasia. Late total occlusion presenting with an acute clinical event seven
      months after the implantation of a paclitaxel drug eluting stent is reported. The
      occlusion developed soon after the interruption of ticlopidine treatment,
      suggesting that the event had a thrombotic genesis and that the risk is not
      confined to the first six month period.

PMID- 11514476
TI  - Architecture of the pulmonary veins: relevance to radiofrequency ablation.
AB  - BACKGROUND: Radiofrequency ablation of tissues in pulmonary veins can eliminate
      paroxysmal atrial fibrillation. OBJECTIVE: To explore the characteristics of
      normal pulmonary veins so as to provide more information relevant to
      radiofrequency ablation. METHODS: 20 structurally normal heart specimens were
      examined grossly. Histological sections were made from 65 pulmonary veins.
      RESULTS: The longest myocardial sleeves were found in the superior veins. The
      sleeves were thickest at the venoatrial junction in the left superior pulmonary
      veins. For the superior veins, the sleeves were thickest along the inferior walls
      and thinnest superiorly. The sleeves were composed mainly of circularly or
      spirally oriented bundles of myocytes with additional bundles that were
      longitudinally or obliquely oriented, sometimes forming mesh-like arrangements.
      Fibrotic changes estimated at between 5% and 70% across three transverse sections
      were seen in 17 veins that were from individuals aged 30 to 72 years.
      CONCLUSIONS: The myocardial architecture in normal pulmonary veins is highly
      variable. The complex arrangement, stretch, and increase in fibrosis may produce
      greater non-uniform anisotropic properties.

PMID- 11514477
TI  - A prospective comparison of echocardiographic wall motion score index and
      radionuclide ejection fraction in predicting outcome following acute myocardial
      infarction.
AB  - OBJECTIVE: To characterise echocardiographic wall motion score index (WMSI) as a
      surrogate measure of left ventricular ejection fraction (EF) following acute
      myocardial infarction (AMI) and to compare its prognostic value with that of EF
      measured by radionuclide ventriculography (RNV). DESIGN: A prospective study to
      compare baseline echocardiographic WMSI with RNV EF in consecutive patients
      thrombolysed for AMI, both performed on the same day before discharge, and their
      relative prognostic values in predicting cardiac events. SETTING: District
      general hospital coronary care unit and cardiology department. PATIENTS: 120
      consecutive patients free of exclusion criteria thrombolysed for AMI and followed
      up for a mean (SD) of 13 (10) months. INTERVENTIONS: None. MAIN OUTCOME MEASURES:
      Correlation coefficients and receiver operating characteristic curve analyses
      plus cardiac event rates at follow up between RNV EF and echocardiographic WMSI.
      RESULTS: WMSI correlated well with RNV EF. The best corresponding WMSIs for EFs
      45%, 40%, and 35% were 0.6, 0.8, and 1.1, respectively. There were 42 cardiac
      events during follow up. Although both RNV EF and WMSI were strong univariate
      predictors of cardiac events, only WMSI independently predicted outcome in a
      multivariate model. All three WMSI cut offs significantly predicted events, while
      an RNV EF cut off of </= 45% v > 45% failed to reach significance. CONCLUSIONS:
      Although both RNV and echocardiographic WMSI strongly predicted cardiac outcome,
      WMSI, a cheaper and more readily available technique, is more discriminatory,
      especially in cases of mild left ventricular dysfunction following AMI.

PMID- 11514478
TI  - Geographic variation in incidence of coronary heart disease in Britain: the
      contribution of established risk factors.
AB  - OBJECTIVE: To determine the extent to which geographic variation in the incidence
      of major coronary heart disease (CHD) in Great Britain may be explained by
      established risk factors. DESIGN: Prospective study. SETTING: 24 British towns
      with widely differing CHD mortality. SUBJECTS: 7735 men followed up from
      screening in 1978-80 for 15 years. MAIN OUTCOME MEASURES: Percentage of variance
      between the towns in major CHD incidence that can be explained by individual
      characteristics of men in the towns. RESULTS: Age standardised incidence rates
      over a 15 year period varied from 0.52% per annum in Maidstone to 1.07% per annum
      in Dewsbury and tended to follow the known pattern of higher rates in Scottish
      and northern English towns and lower rates in southern English towns ("north
      south gradient"). Higher town incidence rates were related to prevalence of
      current cigarette smoking, low physical activity, and low alcohol consumption,
      and to mean body mass index, mean systolic blood pressure, low mean height, and
      prevalence of manual social class, but not to mean serum total cholesterol. The
      95% range for true age adjusted CHD incidence (over 15 years) was estimated as
      0.58-1.03% per annum among British towns. After adjustment for baseline smoking
      status, physical activity, body mass index, alcohol consumption, systolic blood
      pressure, serum total cholesterol, occupational social class, and height, this
      variation was reduced by 50%. A model based on these eight variables accounted
      for the major part of the north-south gradient. CONCLUSIONS: Much of the
      variation in CHD incidence among British towns was accounted for by established
      risk variables. The remaining unexplained variation may be related to measurement
      error in the established risk variables, to environmental factors such as
      climate, or to the combined effect of a wide range of minor risk factors.

PMID- 11514479
TI  - Trends in the prevalence and management of atrial fibrillation in general
      practice in England and Wales, 1994-1998: analysis of data from the general
      practice research database.
AB  - OBJECTIVE: To determine the prevalence of atrial fibrillation in England and
      Wales, and examine trends in its treatment with warfarin and aspirin between 1994
      and 1998. DESIGN: Analysis of data from the general practice research database.
      SETTING: England and Wales. PATIENTS: 1.4 million patients registered with 211
      general practices. MAIN OUTCOME MEASURES: Age and sex specific prevalence rates
      of atrial fibrillation; percentage of patients with atrial fibrillation treated
      with oral anticoagulants or aspirin. RESULTS: The prevalence of atrial
      fibrillation in 1998 was 12.1/1000 in men and 12.7/1000 in women. Prevalence
      increased from less than 1/1000 in under 35 year olds to over 100/1000 in those
      aged 85 years and over. There was a 22% increase in the age standardised
      prevalence of atrial fibrillation in men and a 14% increase in women between 1994
      and 1998. The percentage of patients prescribed oral anticoagulants increased
      from 20% to 34% in men and from 17% to 25% in women. The percentage of men with
      atrial fibrillation prescribed aspirin increased from 26% to 36%, and the
      percentage of women increased from 24% to 36%. Applying the age and sex specific
      prevalence and treatment rates to the population gives an estimate of around 650
      000 cases of atrial fibrillation in England and Wales. The greatest number of
      cases occurs in the 75-84 year old age group. CONCLUSIONS: The number of patients
      in the community with identified atrial fibrillation is increasing. There has
      also been a pronounced increase in the percentage of patients with atrial
      fibrillation prescribed oral anticoagulants or aspirin.

PMID- 11514480
TI  - Coronary artery embolism complicating heart valve surgery: role of mechanical
      thrombectomy.

PMID- 11514481
TI  - Population implications of lipid lowering for prevention of coronary heart
      disease: data from the 1995 Scottish health survey.
AB  - OBJECTIVE: To determine the proportion of the population, firstly, with
      cholesterol >/= 5.0 mmol/l and, secondly, with any cholesterol concentration, who
      might benefit from statin treatment for the following: secondary prevention of
      coronary heart disease (CHD); primary prevention at CHD risk 30%, 20%, 15%, and
      6% over 10 years; and primary prevention at projected CHD risk 20% over 10 years
      (CHD risk at age 60 years if actual age < 60 years). SUBJECTS: Random stratified
      sample of 3963 subjects aged 35-64 years from the Scottish health survey 1995.
      RESULTS: For secondary prevention 7.8% (95% confidence interval (CI) 6.9% to
      8.6%) of the population with cholesterol >/= 5.0 mmol/l would benefit from
      statins. For primary prevention, the prevalence of people at CHD risk 30%, 20%,
      15%, and 6% over 10 years is 1.5% (95% CI 1.2% to 1.9%), 5.4% (95% CI 4.7% to
      6.1%), 9.7% (95% CI 8.8% to 10.6%), and 32.9% (95% CI 31.5% to 34.4%),
      respectively. At projected CHD risk 20% over 10 years, 12.4% (95% CI 11.4% to
      13.5%) would be treated with statins. Removing the 5.0 mmol/l cholesterol
      threshold makes little difference to population prevalence at high CHD risk.
      CONCLUSIONS: Statin treatment would be required for 7.8% of the population for
      secondary prevention. For primary prevention, among other factors, guidelines
      should take into account the number of patients needing treatment at different
      levels of CHD risk when choosing the CHD risk to target. The analysis supports a
      policy of targeting treatment at CHD risk 30% over 10 years as a minimum, as
      recommended in current British guidelines, with a move to treating at CHD risk
      15% over 10 years as resources permit.

PMID- 11514482
TI  - Vasomotor effects of L- and D-arginine in stenotic atheromatous coronary plaque.
AB  - OBJECTIVE: To examine the effects of exogenous L- and D-arginine on coronary
      stenosis vasomotion in relation to stenosis morphology. DESIGN: Intracoronary
      infusions of normal saline, L- and D-arginine (50 and 150 micromol/min), and
      glyceryl trinitrate (250 microg bolus) were given in 24 patients with coronary
      artery disease and stable angina. Coronary stenoses were classified as smooth or
      complex (irregular borders). The diameter of the coronary stenoses and their
      adjacent reference segments was measured by computed quantitative angiography.
      RESULTS: During L-arginine infusion a larger proportion of complex stenoses than
      smooth stenoses dilated by >/= 10% (p < 0.01), and the magnitude of dilatation
      was greater at the site of complex stenoses (p < 0.05). Irrespective of the type
      of morphology there was a positive correlation (p < 0.01) between the severity of
      stenoses and the magnitude of vasodilatation to L-arginine. The response to
      glyceryl trinitrate was similar in the two groups. No significant change was
      found in either group in response to D-arginine. CONCLUSIONS: In patients with
      coronary artery disease, coronary stenoses-particularly those of complex
      morphology-dilate in response to the administration of L-arginine but not D
      arginine. This finding is consistent with partial deficiency of the substrate for
      nitric oxide synthesis, L-arginine, at the site of complex stenoses.

PMID- 11514483
TI  - Randomised comparison of coronary stenting with and without balloon predilatation
      in selected patients.
AB  - BACKGROUND: The SWIBAP (stent without balloon predilatation) prospective
      randomised trial was designed to compare direct coronary stenting with stenting
      preceded by lesion predilatation with an angioplasty balloon. OBJECTIVE: To
      determine the feasibility and safety of direct stenting in non-complex coronary
      lesions in a prospective study. PATIENTS AND DESIGN: All patients < 76 years of
      age scheduled to undergo angioplasty of a non-complex, non-calcified lesion in a
      coronary artery of > 3.0 mm, who granted their informed consent, were randomised
      into the trial. In group I, the stent was placed without balloon predilatation,
      while in group II stent implantation was preceded by balloon predilatation. The
      primary end point was the angiographic result according to procedure assigned by
      randomisation. An intravascular ultrasound substudy was performed in 60 patients.
      RESULTS: Stent implantation was successful without predilatation in 192 of the
      197 group I patients (97.5%), and with predilatation in 197 of the 199 group II
      patients (99%) (NS). No in-hospital stent thrombosis or death occurred. Overall
      procedural times, fluoroscopy times, and volumes of contrast agent given (mean
      (SD)) in group I v group II were 23.50 (13.54) min v 27.96 (15.23) min (p =
      0.002), 6.04 (4.13) min v 6.67 (3.65) min (NS), and 135 (65) ml v 157 (62) ml (p
      < 0.001), respectively. No major adverse cardiovascular events had occurred by 30
      days. CONCLUSIONS: The feasibility and safety of direct stenting of selected and
      non-complex coronary lesions is confirmed. This technique was as successful as
      the conventional approach and was associated with a minor reduction in
      fluoroscopic exposure and procedure time and the administration of less contrast
      agent.

PMID- 11514484
TI  - Systemic sclerosis involving the heart.

PMID- 11514485
TI  - Four year follow up of aortic valve replacement for isolated aortic stenosis: a
      link between reduction in pressure overload, regression of left ventricular
      hypertrophy, and diastolic function.
AB  - OBJECTIVE: To evaluate changes in left ventricular function and the impact of
      ventricular hypertrophy and pressure gradient early and late after aortic valve
      replacement in patients with isolated aortic stenosis. DESIGN: 41 patients with
      isolated aortic stenosis and normal systolic function underwent cross sectional
      and Doppler echocardiography two months before and two weeks and four years after
      aortic valve replacement. RESULTS: Early after the operation, left ventricular
      mass index (mean (SD)) decreased from 187 (44) g/m(2) to 179 (46) g/m(2), because
      of a reduction in end diastolic diameter (p < 0.05). Aortic pressure gradients
      were reduced, as expected. Isovolumic relaxation time was reduced from 93 (20) ms
      to 78 (12) ms, and deceleration time from 241 (102) ms to 205 (77) ms (p < 0.05).
      At four years, left ventricular mass index was further reduced to 135 (30) g/m(2)
      (p < 0.01) as a result of wall thickness reduction in the interventricular septum
      (from 14 (1.6) mm to 12 (1.4) mm, p < 0.01) and the posterior wall (from 14 (1.6)
      mm to 12 (1.3) mm, p < 0.01). Diastolic function, expressed by a reduction in
      isovolumic relaxation time from 93 (20) ms to 81 (15) ms (p < 0.01) and
      deceleration time from 241 (102) ms to 226 (96) ms (p < 0.05), remained improved.
      Prolonged isovolumic relaxation time was associated with significant septal and
      posterior wall hypertrophy (wall thickness > 13 mm) (p < 0.05), whereas prolonged
      deceleration time was related to high residual gradient (peak gradient > 30 mm Hg
      ) (p < 0.01). CONCLUSIONS: Left ventricular diastolic function improves early
      after surgery for aortic stenosis in parallel with the reduction in the aortic
      gradient. However, prolongation of Doppler indices of myocardial relaxation and
      ventricular filling is observed in patients with significant left ventricular
      hypertrophy and a residual pressure gradient early after surgery. At four years
      postoperatively, diastolic function remains improved.

PMID- 11514486
TI  - Aortico-right ventricular tunnel with pulmonary stenosis in a neonate.

PMID- 11514488
TI  - Penetrating heart injury from second world war.

PMID- 11514487
TI  - Nurse led shared care for patients on the waiting list for coronary artery bypass
      surgery: a randomised controlled trial.
AB  - OBJECTIVE: To evaluate the effectiveness of a nurse led shared care programme to
      improve coronary heart disease risk factor levels and general health status and
      to reduce anxiety and depression in patients awaiting coronary artery bypass
      grafting (CABG). DESIGN: Randomised controlled trial. SETTING: Community, January
      1997 to March 1998. STUDY GROUPS: 98 (75 male) consecutive patients were
      recruited to the study within one month of joining the waiting list for elective
      CABG at Glasgow Royal Infirmary University NHS Trust. Patients were randomly
      assigned to usual care (control; n = 49) or a nurse led intervention programme (n
      = 49). INTERVENTION: A shared care programme consisting of health education and
      motivational interviews, according to individual need, was carried out monthly.
      Care was provided in the patients' own homes by the community based cardiac
      liaison nurse alternating with the general practice nurse at the practice clinic.
      OUTCOME MEASURES: Smoking status, obesity, physical activity, anxiety and
      depression, general health status, and proportion of patients exceeding target
      values for blood pressure, plasma cholesterol, and alcohol intake. RESULTS:
      Compared with patients who received usual care, those participating in the nurse
      led programme were more likely to stop smoking (25% v 2%, p = 0.001) and to
      reduce obesity (body mass index > 30 kg/m(2)) (16.3% v 8.1%, p = 0.01). Target
      systolic blood pressure improved by 19.8% compared with a 10.7% decrease in the
      control group (p = 0.001) and target diastolic blood pressure improved by 21.5%
      compared with 10.2% in the control group (p = 0.000). However, there was no
      significant difference between groups in the proportion of patients with
      cholesterol concentrations exceeding target values. There was a significant
      improvement in general health status scores across all eight domains of the 36
      item short form health survey with changes in difference in mean scores between
      the groups ranging from 8.1 (p = 0.005) to 36.1 (p < 0.000). Levels of anxiety
      and depression improved (p < 0.000) and there was improvement in time spent being
      physically active (p < 0.000). CONCLUSIONS: This nurse led shared care
      intervention was shown to be effective for improving care for patients on the
      waiting list for CABG.

PMID- 11514489
TI  - Quantitative contrast echocardiographic assessment of collateral derived
      myocardial perfusion during elective coronary angioplasty.
AB  - OBJECTIVE: To determine whether myocardial contrast echocardiography can be used
      to quantify collateral derived myocardial flow in humans. METHODS: In 25 patients
      undergoing coronary angioplasty, a collateral flow index (CFI) was determined
      using intracoronary wedge pressure distal to the stenosis to be dilated, with
      simultaneous mean aortic pressure measurements. During balloon occlusion, echo
      contrast was injected into both main coronary arteries simultaneously.
      Echocardiography of the collateral receiving myocardial area was performed. The
      time course of myocardial contrast enhancement in images acquired at end diastole
      was quantified by measuring pixel intensities (256 grey units) within a region of
      interest. Perfusion variables, such as background subtracted peak pixel intensity
      and contrast transit rate, were obtained from a fitted gamma variate curve.
      RESULTS: 16 patients had a left anterior descending coronary artery stenosis,
      four had a left circumflex coronary artery stenosis, and five had a right
      coronary artery stenosis. The mean (SD) CFI was 19 (12)% (range 0-47%). Mean
      contrast transit rate was 11 (8) seconds. In 17 patients, a significant
      collateral contrast effect was observed (defined as peak pixel intensity more
      than the mean + 2 SD of background). Peak pixel intensity was linearly related to
      CFI in patients with a significant contrast effect (p = 0.002, r = 0.69) as well
      as in all patients (p = 0.0003, r = 0.66). CONCLUSIONS: Collateral derived
      perfusion of myocardial areas at risk can be demonstrated using intracoronary
      echo contrast injections. The peak echo contrast effect is directly related to
      the magnitude of collateral flow.

PMID- 11514490
TI  - The Fontan procedure in adults.
AB  - SETTING: Tertiary adult congenital cardiac referral centre. DESIGN: Retrospective
      cross sectional analysis. OBJECTIVES: To report our 20 year experience with adult
      Fontan operations, and to compare late outcome in patients with single ventricle
      with definitive aortopulmonary or cavopulmonary shunt palliation. PATIENTS AND
      MAIN OUTCOME MEASURES: Patients older than 18 years undergoing Fontan operation
      between 1 January 1982 and 31 December 1998 were identified. Mortality and late
      outcome were derived from hospital records. These patients were compared with a
      cohort of 50 adults with single ventricle who had not undergone a Fontan
      operation. RESULTS: 61 adults, median age 36 years (range 18-47 years), with a
      median follow up of 10 years (range 0-21 years) were identified. Actuarial
      survival was 80% at one year, 76% at five years, 72% at 10 years, and 67% at 15
      years. Compared with before the Fontan operation, more patients were in New York
      Heart Association (NYHA) functional class I or II at the latest follow up (80% v
      58%, p < 0.001). Systolic ventricular function deteriorated during follow up such
      that 34% had moderate to severe ventricular dysfunction at the latest follow up
      compared with 5% before Fontan (p < 0.001). Arrhythmia increased with time (10%
      before Fontan v 57% after 10 years, p < 0.001). Fontan patients had improved NYHA
      functional class, ventricular function, atrioventricular regurgitation, and fewer
      arrhythmias than the non-Fontan group at the latest follow up. CONCLUSION: The
      Fontan operation in adults has acceptable early and late mortality. Functional
      class, systolic ventricular function, atrioventricular regurgitation, and
      arrhythmia deteriorate late after surgery but to a lesser degree than in non
      Fontan patients with a single ventricle.

PMID- 11514491
TI  - Interleukin 1 receptor antagonist gene polymorphism and restenosis after coronary
      angioplasty.
AB  - BACKGROUND: Percutaneous transluminal coronary angioplasty (PTCA) is limited by
      the recurrence of luminal stenosis, which occurs in up to 50% of procedures. It
      has been shown that patient specific factors, perhaps genes, contribute to this
      process. OBJECTIVE: To determine whether completion of healing after PTCA is part
      of an acute self limiting inflammatory process and whether polymorphism at
      important inflammatory gene loci might determine susceptibility to restenosis
      after PTCA. DESIGN: DNA samples were collected from 171 patients attending for
      elective PTCA in Sheffield (S) and Leicester (L), who were scheduled to undergo
      follow up angiography (at four months (L) or six months (S)) as part of other
      restenosis studies. At follow up angiography, the patients were separated into
      restenosers (> 50% luminal narrowing) and non-restenosers (< 50% luminal
      narrowing). Four DNA polymorphisms within interleukin 1 (IL-1) related loci (IL
      1A (-889), IL-1B (-511), IL-1B (+3954), and IL-1RN intron 2 VNTR (variable number
      tandem repeat)) were genotyped using methods based on polymerase chain reaction.
      Significance was assessed by chi(2) analysis of the relevant contingency table,
      and the magnitude of effect was estimated by calculating odds ratios. The Mantel
      Haenszel (MH) test was applied to summarise data across the two populations.
      RESULTS: Allele 2 at IL-1RN (IL-1RN*2) was significantly over represented in the
      non-restenoser group (L+S, 34% v 23% in restenosers). Furthermore, IL-1RN*2
      homozygosity was increased in the non-restenoser population compared with the
      restenosers (MH test: p = 0.0196 (L+S); p = 0.031 (L+S, single vessel disease
      only), and the effect seemed to be restricted to the single vessel disease
      subpopulation. For other polymorphism within IL-1 related loci no significant
      associations were found with either restenosis or non-restenosis. CONCLUSIONS: IL
      1RN*2 may be associated with protection from restenosis after PTCA for
      individuals with single vessel disease. As this polymorphism has functional
      significance, this finding suggests that alteration in an individual's
      inflammatory predisposition may modulate the blood vessel response to injury.

PMID- 11514492
TI  - Subarachnoid haemorrhage presenting as acute myocardial infarction with
      electromechanical dissociation arrest.

PMID- 11514493
TI  - Myocardial infarction rates are higher on weekends than on weekdays in middle
      aged French men.

PMID- 11514494
TI  - Myocardial integrated ultrasound backscatter in patients with Duchenne's
      progressive muscular dystrophy.

PMID- 11514495
TI  - Differential diagnosis of restrictive cardiomyopathy and constrictive
      pericarditis.

PMID- 11514496
TI  - Dizziness and syncope in adolescence.

PMID- 11514497
TI  - Permanent pacing: new indications.

PMID- 11514498
TI  - Fulminant eosinophilic endomyocarditis in an asthmatic patient treated with
      pranlukast after corticosteroid withdrawal.
AB  - Several cases of eosinophilic conditions including Churg-Strauss syndrome have
      been reported in association with the use of cysteinyl leukotriene receptor
      antagonists, including zafirlukast, montelukast, and pranlukast, in asthmatic
      patients. The case of a 26 year old woman with a three year history of asthma,
      rhinitis, and nasal polyps is reported in whom eosinophilia, pulmonary
      infiltrates, and fulminant eosinophilic endomyocarditis accompanied by
      cardiogenic shock developed during pranlukast treatment after corticosteroid
      withdrawal. Acute necrotising eosinophilic endomyocarditis was confirmed by
      endomyocardial biopsy. The patient recovered after intensive treatment, including
      mechanical assistance involving intra-aortic balloon pumping and steroid pulse
      therapy, along with the discontinuation of pranlukast. It is recommended that
      careful attention must be paid to signs of a systemic eosinophilic condition or
      even fulminant eosinophilic myocarditis in asthmatic patients who have begun
      treatment with antileukotriene drugs following withdrawal of steroids.

PMID- 11514499
TI  - Papillary muscle calcification after inferoposterior myocardial infarction.
AB  - Extensive papillary muscle calcification is quite a rare finding in
      echocardiographic examinations. A case of a 71 year old man with isolated
      calcification of the papillary muscles, detected by fluoroscopy and confirmed by
      echocardiography, is presented. Intracardiac calcifications in patients with
      prior right coronary artery occlusion and mitral regurgitation should suggest the
      possibility of posteromedial papillary muscle calcification and dysfunction.

PMID- 11514500
TI  - Left internal mammary graft stenosis and restenosis following angioplasty and
      stenting.
AB  - Coronary bypass grafts using the internal mammary artery usually have an
      excellent record of success and long term patency. We report a 42 year old man
      who initially presented with a history of atypical left sided chest pain, who had
      coronary artery bypass surgery for a severe stenosis in his proximal left
      anterior descending coronary artery (LAD) and moderate stenosis of his proximal
      circumflex artery, with his LIMA being grafted to his mid-LAD and a saphenous
      venous graft to the proximal LAD. He subsequently developed multiple stenoses in
      the LIMA graft which required coronary augioplasty and stenting, on more than one
      occasion, in view of very rapid restenosis within the LIMA graft.

PMID- 11514501
TI  - Long term inhalation of iloprost in a child with primary pulmonary hypertension:
      an alternative to continuous infusion.
AB  - Primary pulmonary hypertension is a rare disease in childhood associated with a
      poor prognosis. However, during the past 10 years, pulmonary vasodilator
      treatment has somewhat improved its prognosis. Long term continuous infusion of
      prostacyclin (epoprostenol) has been shown to improve physical capacity and to
      reduce mortality in primary and secondary pulmonary hypertension. It has been
      reported in adults that daily repetitive inhalation of iloprost, a prostacyclin
      analogue, seems also suitable for long term therapy of pulmonary hypertension.
      Repetitive inhalation of iloprost was administered to a 5 year old boy with
      severe primary pulmonary hypertension. He showed continuous clinical improvement
      without any side effects over the three years of treatment. This treatment may
      offer an alternative to continuous intravenous prostacyclin infusion and obviates
      the need for a permanent central venous catheter.

PMID- 11514502
TI  - Overexpression of the MexEF-OprN multidrug efflux system affects cell-to-cell
      signaling in Pseudomonas aeruginosa.
AB  - Intrinsic and acquired antibiotic resistance of the nosocomial pathogen
      Pseudomonas aeruginosa is mediated mainly by the expression of several efflux
      pumps of broad substrate specificity. Here we report that nfxC type mutants,
      overexpressing the MexEF-OprN efflux system, produce lower levels of
      extracellular virulence factors than the susceptible wild type. These include
      pyocyanin, elastase, and rhamnolipids, three factors controlled by the las and
      rhl quorum-sensing systems of P. aeruginosa. In agreement with these observations
      are the decreased transcription of the elastase gene lasB and the
      rhamnosyltransferase genes rhlAB measured in nfxC type mutants. Expression of the
      lasR and rhlR regulator genes was not affected in the nfxC type mutant. In
      contrast, transcription of the C4-homoserine lactone (C4-HSL) autoinducer
      synthase gene rhlI was reduced by 50% in the nfxC type mutant relative to that in
      the wild type. This correlates with a similar decrease in C4-HSL levels detected
      in supernatants of the nfxC type mutant. Transcription of an rhlAB-lacZ fusion
      could be partially restored by the addition of synthetic C4-HSL and Pseudomonas
      quinolone signal (PQS). It is proposed that the MexEF-OprN efflux pump affects
      intracellular PQS levels.

PMID- 11514503
TI  - Feedback regulation of glucose transporter gene transcription in Kluyveromyces
      lactis by glucose uptake.
AB  - In the respirofermentative yeast Kluyveromyces lactis, only a single genetic
      locus encodes glucose transporters that can support fermentative growth. This
      locus is polymorphic in wild-type isolates carrying either KHT1 and KHT2, two
      tandemly arranged HXT-like genes, or RAG1, a low-affinity transporter gene that
      arose by recombination between KHT1 and KHT2. Here we show that KHT1 is a glucose
      induced gene encoding a low-affinity transporter very similar to Rag1p. Kht2p has
      a lower K(m) (3.7 mM) and a more complex regulation. Transcription is high in the
      absence of glucose, further induced by low glucose concentrations, and repressed
      at higher glucose concentrations. The response of KHT1 and KHT2 gene regulation
      to high but not to low concentrations of glucose depends on glucose transport.
      The function of either Kht1p or Kht2p is sufficient to mediate the characteristic
      response to high glucose, which is impaired in a kht1 kht2 deletion mutant. Thus,
      the KHT genes are subject to mutual feedback regulation. Moreover, glucose
      repression of the endogenous beta-galactosidase (LAC4) promoter and glucose
      induction of pyruvate decarboxylase were abolished in the kht1 kht2 mutant. These
      phenotypes could be partially restored by HXT gene family members from
      Saccharomyces cerevisiae. The results indicate that the specific responses to
      high but not to low glucose concentrations require a high rate of glucose uptake.

PMID- 11514504
TI  - Absence of the outer membrane phospholipase A suppresses the temperature
      sensitive phenotype of Escherichia coli degP mutants and induces the Cpx and
      sigma(E) extracytoplasmic stress responses.
AB  - DegP is a periplasmic protease that is a member of both the sigma(E) and Cpx
      extracytoplasmic stress regulons of Escherichia coli and is essential for
      viability at temperatures above 42 degrees C. [U-(14)C]acetate labeling
      experiments demonstrated that phospholipids were degraded in degP mutants at
      elevated temperatures. In addition, chloramphenicol acetyltransferase, beta
      lactamase, and beta-galactosidase assays as well as sodium dodecyl sulfate
      polyacrylamide gel electrophoresis analysis indicated that large amounts of
      cellular proteins are released from degP cells at the nonpermissive temperature.
      A mutation in pldA, which encodes outer membrane phospholipase A (OMPLA), was
      found to rescue degP cells from the temperature-sensitive phenotype. pldA degP
      mutants had a normal plating efficiency at 42 degrees C, displayed increased
      viability at 44 degrees C, showed no degradation of phospholipids, and released
      far lower amounts of cellular protein to culture supernatants. degP and pldA degP
      mutants containing chromosomal lacZ fusions to Cpx and sigma(E) regulon promoters
      indicated that both regulons were activated in the pldA mutants. The
      overexpression of the envelope lipoprotein, NlpE, which induces the Cpx regulon,
      was also found to suppress the temperature-sensitive phenotype of degP mutants
      but did not prevent the degradation of phospholipids. These results suggest that
      the absence of OMPLA corrects the degP temperature-sensitive phenotype by
      inducing the Cpx and sigma(E) regulons rather than by inactivating the
      phospholipase per se.

PMID- 11514505
TI  - DNA microarray-based identification of genes controlled by autoinducer 2
      stimulated quorum sensing in Escherichia coli.
AB  - Bacterial cell-to-cell communication facilitates coordinated expression of
      specific genes in a growth rate-II and cell density-dependent manner, a process
      known as quorum sensing. While the discovery of a diffusible Escherichia coli
      signaling pheromone, termed autoinducer 2 (AI-2), has been made along with
      several quorum sensing genes, the overall number and coordination of genes
      controlled by quorum sensing through the AI-2 signal has not been studied
      systematically. We investigated global changes in mRNA abundance elicited by the
      AI-2 signaling molecule through the use of a luxS mutant that was unable to
      synthesize AI-2. Remarkably, 242 genes, comprising ca. 5.6% of the E. coli
      genome, exhibited significant transcriptional changes (either induction or
      repression) in response to a 300-fold AI-2 signaling differential, with many of
      the identified genes displaying high induction levels (more than fivefold).
      Significant induction of ygeV, a putative sigma(54)-dependent transcriptional
      activator, and yhbH, a sigma(54) modulating protein, suggests sigma(54) may be
      involved in E. coli quorum sensing.

PMID- 11514506
TI  - Catabolite repression of the citrate fermentation genes in Klebsiella pneumoniae:
      evidence for involvement of the cyclic AMP receptor protein.
AB  - Klebsiella pneumoniae is able to grow anaerobically with citrate as a sole carbon
      and energy source by a fermentative pathway involving the Na(+)-dependent citrate
      carrier CitS, citrate lyase, and oxaloacetate decarboxylase. The corresponding
      genes are organized in the divergent citC and citS operons, whose expression is
      strictly dependent on the citrate-sensing CitA-CitB two-component system.
      Evidence is provided here that the citrate fermentation genes are subject to
      catabolite repression, since anaerobic cultivation with a mixture of citrate and
      glucose or citrate and gluconate resulted in diauxic growth. Glucose, gluconate,
      and also glycerol decreased the expression of a chromosomal citS-lacZ fusion by
      60 to 75%, whereas a direct inhibition of the citrate fermentation enzymes was
      not observed. The purified cyclic AMP (cAMP) receptor protein (CRP) of K.
      pneumoniae bound to two sites in the citC-citS intergenic region, which were
      centered at position -41.5 upstream of the citC and citS transcriptional start
      sites. Binding was apparently stimulated by the response regulator CitB. These
      data indicate that catabolite repression of the citrate fermentation genes is
      exerted by CRP and that in the absence of repressing carbon sources the cAMP-CRP
      complex serves to enhance the basal, CitB-dependent transcription level.

PMID- 11514507
TI  - Three target genes for the transcriptional activator Cat8p of Kluyveromyces
      lactis: acetyl coenzyme A synthetase genes KlACS1 and KlACS2 and lactate permease
      gene KlJEN1.
AB  - The aerobic yeast Kluyveromyces lactis and the predominantly fermentative
      Saccharomyces cerevisiae share many of the genes encoding the enzymes of carbon
      and energy metabolism. The physiological features that distinguish the two yeasts
      appear to result essentially from different organization of regulatory circuits,
      in particular glucose repression and gluconeogenesis. We have isolated the KlCAT8
      gene (a homologue of S. cerevisiae CAT8, encoding a DNA binding protein) as a
      multicopy suppressor of a fog1 mutation. The Fog1 protein is a homologue of the
      Snf1 complex components Gal83p, Sip1p, and Sip2p of S. cerevisiae. While CAT8
      controls the key enzymes of gluconeogenesis in S. cerevisiae, KlCAT8 of K. lactis
      does not (I. Georis, J. J. Krijger, K. D. Breunig, and J. Vandenhaute, Mol. Gen.
      Genet. 264:193-203, 2000). We therefore examined possible targets of KlCat8p. We
      found that the acetyl coenzyme A synthetase genes, KlACS1 and KlACS2, were
      specifically regulated by KlCAT8, but very differently from the S. cerevisiae
      counterparts. KlACS1 was induced by acetate and lactate, while KlACS2 was induced
      by ethanol, both under the control of KlCAT8. Also, KlJEN1, encoding the lactate
      inducible and glucose-repressible lactate permease, was found under a tight
      control of KlCAT8.

PMID- 11514508
TI  - Gene cluster on pAO1 of Arthrobacter nicotinovorans involved in degradation of
      the plant alkaloid nicotine: cloning, purification, and characterization of 2,6
      dihydroxypyridine 3-hydroxylase.
AB  - A 27,690-bp gene cluster involved in the degradation of the plant alkaloid
      nicotine was characterized from the plasmid pAO1 of Arthrobacter nicotinovorans.
      The genes of the heterotrimeric, molybdopterin cofactor (MoCo)-, flavin adenine
      dinucleotide (FAD)-, and [Fe-S] cluster-dependent 6-hydroxypseudooxynicotine
      (ketone) dehydrogenase (KDH) were identified within this cluster. The gene of the
      large MoCo subunit of KDH was located 4,266 bp from the FAD and [Fe-S] cluster
      subunit genes. Deduced functions of proteins encoded by open reading frames
      (ORFs) of the cluster were correlated to individual steps in nicotine
      degradation. The gene for 2,6-dihydroxypyridine 3-hydroxylase was cloned and
      expressed in Escherichia coli. The purified homodimeric enzyme of 90 kDa
      contained 2 mol of tightly bound FAD per mol of dimer. Enzyme activity was
      strictly NADH-dependent and specific for 2,6-dihydroxypyridine. 2,3
      Dihydroxypyridine and 2,6-dimethoxypyridine acted as irreversible inhibitors.
      Additional ORFs were shown to encode hypothetical proteins presumably required
      for holoenzyme assembly, interaction with the cell membrane, and transcriptional
      regulation, including a MobA homologue predicted to be specific for the synthesis
      of the molybdopterin cytidine dinucleotide cofactor.

PMID- 11514509
TI  - Two similar gene clusters coding for enzymes of a new type of aerobic 2
      aminobenzoate (anthranilate) metabolism in the bacterium Azoarcus evansii.
AB  - In the beta-proteobacterium Azoarcus evansii, the aerobic metabolism of 2
      aminobenzoate (anthranilate), phenylacetate, and benzoate proceeds via three
      unprecedented pathways. The pathways have in common that all three substrates are
      initially activated to coenzyme A (CoA) thioesters and further processed in this
      form. The two initial steps of 2-aminobenzoate metabolism are catalyzed by a 2
      aminobenzoate-CoA ligase forming 2-aminobenzoyl-CoA and by a 2-aminobenzoyl-CoA
      monooxygenase/reductase (ACMR) forming 2-amino-5-oxo-cyclohex-1-ene-1-carbonyl
      CoA. Eight genes possibly involved in this pathway, including the genes encoding
      2-aminobenzoate-CoA ligase and ACMR, were detected, cloned, and sequenced. The
      sequence of the ACMR gene showed that this enzyme is an 87-kDa fusion protein of
      two flavoproteins, a monooxygenase (similar to salicylate monooxygenase) and a
      reductase (similar to old yellow enzyme). Besides the genes for the initial two
      enzymes, genes for three enzymes of a beta-oxidation pathway were found. A
      substrate binding protein of an ABC transport system, a MarR-like regulator, and
      a putative translation inhibitor protein were also encoded by the gene cluster.
      The data suggest that, after monooxygenation/reduction of 2-aminobenzoyl-CoA, the
      nonaromatic CoA thioester intermediate is metabolized further by beta-oxidation.
      This implies that all subsequent intermediates are CoA thioesters and that the
      alicyclic carbon ring is not cleaved oxygenolytically. Surprisingly, the cluster
      of eight genes, which form an operon, is duplicated. The two copies differ only
      marginally within the coding regions but differ substantially in the respective
      intergenic regions. Both copies of the genes are coordinately expressed in cells
      grown aerobically on 2-aminobenzoate.

PMID- 11514510
TI  - Molecular evidence for independent occurrence of IS6110 insertions at the same
      sites of the genome of Mycobacterium tuberculosis in different clinical isolates.
AB  - Several characteristics of Mycobacterium tuberculosis (e.g., conserved genome and
      low growth rate) have severely restricted the study of the microorganism. The
      discovery of IS6110 raised hopes of overcoming these obstacles. However, our
      knowledge of this IS element is relatively limited; even its two basic
      characteristics (transposition mechanism and target site selection) are far from
      well understood. In this study, IS6110 insertions in ipl loci (iplA and iplB) in
      two collections of clinical isolates of M. tuberculosis from different geographic
      locations, one from Scotland and the other from Thailand, were investigated. Five
      different IS6110 insertions in the loci were identified: ipl-4::IS6110, ipl
      5::IS6110, ipl-11::IS6110, ipl-12::IS6110, and ipl-13::IS6110. An attempt to
      establish the phylogenetic relationship of the isolates containing these
      insertions was unsuccessful, suggesting that some of these insertions may have
      arisen from more than one event. This possibility is further supported by the
      observation that IS6110 copies existed in the same site but with different
      orientations in different isolates, and the insertion site of ipl-1::IS6110
      harbored IS6110 copies in both iplA and iplB in different strains. All these
      suggest the independent occurrence of IS6110 insertions at the same sites of the
      genome of M. tuberculosis in different clinical isolates. The implications of
      this finding are discussed.

PMID- 11514511
TI  - Involvement of the TonB system in tolerance to solvents and drugs in Pseudomonas
      putida DOT-T1E.
AB  - Pseudomonas putida DOT-T1E is able to grow with glucose as the carbon source in
      liquid medium with 1% (vol/vol) toluene or 17 g of (123 mM) p-hydroxybenzoate
      (4HBA) per liter. After random mini-Tn5'phoA-Km mutagenesis, we isolated the
      mutant DOT-T1E-PhoA5, which was more sensitive than the wild type to 4HBA (growth
      was prevented at 6 g/liter) and toluene (the mutant did not withstand sudden
      toluene shock). Susceptibility to toluene and 4HBA resulted from the reduced
      efflux of these compounds from the cell, as revealed by accumulation assays with
      (14)C-labeled substrates. The mutant was also more susceptible to a number of
      antibiotics, and its growth in iron-deficient minimal medium was inhibited in the
      presence of ethylenediamine-di(o-hydroxyphenylacetic acid (EDDHA). Cloning the
      mutation in the PhoA5 strain and sequencing the region adjacent showed that the
      mini-Tn5 transposor interrupted the exbD gene, which forms part of the exbBD tonB
      operon. Complementation by the exbBD and tonB genes cloned in pJB3-Tc restored
      the wild-type characteristics to the PhoA5 strain.

PMID- 11514512
TI  - Regulated secretion of YopN by the type III machinery of Yersinia enterocolitica.
AB  - During infection, Yersinia enterocolitica exports Yop proteins via a type III
      secretion pathway. Secretion is activated when the environmental concentration of
      calcium ions is below 100 microM (low-calcium response). Yersiniae lacking yopN
      (lcrE), yscB, sycN, or tyeA do not inactivate the type III pathway even when the
      concentration of calcium is above 100 microM (calcium-blind phenotype). Purified
      YscB and SycN proteins form cytoplasmic complexes that bind a region including
      amino acids 16 to 100 of YopN, whereas TyeA binds YopN residues 101 to 294.
      Translational fusion of yopN gene sequences to the 5' end of the npt reporter
      generates hybrid proteins that are transported by the type III pathway. The
      signal necessary and sufficient for the type III secretion of hybrid proteins is
      located within the first 15 codons of yopN. Expression of plasmid-borne yopN, but
      not of yopN(1-294)-npt, complements the calcium-blind phenotype of yopN mutants.
      Surprisingly, yopN mutants respond to environmental changes in calcium
      concentration and secrete YopN(1-294)-Npt in the absence but not in the presence
      of calcium. tyeA is required for the low-calcium regulation of YopN(1-294)-Npt
      secretion, whereas sycN and yscB mutants fail to secrete YopN(1-294)-Npt in the
      presence of calcium. Experiments with yopN-npt fusions identified two other
      signals that regulate the secretion of YopN. yopN codons 16 to 100 prevent the
      entry of YopN into the type III pathway, a negative regulatory effect that is
      overcome by expression of yscB and sycN. The portion of YopN encoded by codons
      101 to 294 prevents transport of the polypeptide across the bacterial double
      membrane envelope in the presence of functional tyeA. These data support a model
      whereby YopN transport may serve as a regulatory mechanism for the activity of
      the type III pathway. YscB/SycN binding facilitates the initiation of YopN into
      the type III pathway, whereas TyeA binding prevents transport of the polypeptide
      across the bacterial envelope. Changes in the environmental calcium concentration
      relieve the TyeA-mediated regulation, triggering YopN transport and activating
      the type III pathway.

PMID- 11514513
TI  - DnaK chaperone-mediated control of activity of a sigma(32) homolog (RpoH) plays a
      major role in the heat shock response of Agrobacterium tumefaciens.
AB  - RpoH (Escherichia coli sigma(32) and its homologs) is the central regulator of
      the heat shock response in gram-negative proteobacteria. Here we studied salient
      regulatory features of RpoH in Agrobacterium tumefaciens by examining its
      synthesis, stability, and activity while increasing the temperature from 25 to 37
      degrees C. Heat induction of RpoH synthesis occurred at the level of
      transcription from an RpoH-dependent promoter, coordinately with that of DnaK,
      and followed by an increase in the RpoH level. Essentially normal induction of
      heat shock proteins was observed even with a strain that was unable to increase
      the RpoH level upon heat shock. Moreover, heat-induced accumulation of dnaK mRNA
      occurred without protein synthesis, showing that preexisting RpoH was sufficient
      for induction of the heat shock response. These results suggested that
      controlling the activity, rather than the amount, of RpoH plays a major role in
      regulation of the heat shock response. In addition, increasing or decreasing the
      DnaK-DnaJ chaperones specifically reduced or enhanced the RpoH activity,
      respectively. On the other hand, the RpoH protein was normally stable and
      remained stable during the induction phase but was destabilized transiently
      during the adaptation phase. We propose that the DnaK-mediated control of RpoH
      activity plays a primary role in the induction of heat shock response in A.
      tumefaciens, in contrast to what has been found in E. coli.

PMID- 11514514
TI  - Microaerophilic induction of the alpha-crystallin chaperone protein homologue
      (hspX) mRNA of Mycobacterium tuberculosis.
AB  - Among the products that are expressed when Mycobacterium tuberculosis undergoes
      hypoxic shiftdown to nonreplicating persistence (NRP) is the alpha-crystallin
      chaperone protein homologue (Acr). This expression coincides with the previously
      reported appearance of a respiratory type of nitrate reductase activity, the
      increase in glycine dehydrogenase activity, and the production of a unique
      antigen, URB-1. In a timed sampling study, using a slowly stirred oxygen
      depletion culture model, we have demonstrated that the hspX mRNA that codes for
      Acr protein as well as the protein itself is induced just as the bacilli enter
      the microaerophilic NRP stage 1 (NRP-1). In contrast to the induction observed
      for hspX mRNA, levels of 16S rRNA, fbpB mRNA (encoding the 85B alpha antigen),
      and aroB mRNA (encoding dehydroquinate synthase) demonstrate relatively small to
      no change upon entering NRP-1. Acr protein was shown to be identical to URB-1 by
      Western analysis with anti-URB-1 antibody. The fact that antibody to Acr is found
      in a high percentage of tuberculosis patients suggests that the hypoxic shiftdown
      of tubercle bacilli to the NRP state that occurs in vitro, resulting in
      production of the alpha-crystallin protein, occurs in vivo as well. Simultaneous
      abrupt increases in hspX mRNA and Acr protein suggest that Acr protein expression
      is controlled at the level of transcription.

PMID- 11514515
TI  - L-threonine export: use of peptides to identify a new translocator from
      Corynebacterium glutamicum.
AB  - Bacterial mechanisms for the uptake of peptides and their hydrolysis to amino
      acids are known in great detail, whereas much less is known about the fates of
      the peptide-derived amino acids. We show that the addition of L-threonine
      containing di- or tripeptides results in reduction of the growth of
      Corynebacterium glutamicum, with concomitant high intracellular accumulation of L
      threonine to up to 130 mM. Using transposon mutagenesis and isolation of mutants
      with increased Thr peptide sensitivity, nine open reading frames (ORFs) were
      identified, almost all encoding hypothetical proteins of unknown function. Three
      ORFs encode membrane proteins. Their individual functional characterizations in
      the wild-type background led to the identification of thrE. Upon thrE
      overexpression, growth is no longer sensitive to the presence of the Thr peptide,
      and L-threonine is exported at a rate of 3.8 nmol min(-1) mg of dry weight(-1),
      whereas the rate of export of a thrE inactivation mutant is reduced to 1.1 nmol
      min(-1) mg of dry weight(-1). In addition to L-threonine, L-serine is also a
      substrate for the exporter. The exporter exhibits nine predicted transmembrane
      spanning helices with long charged C and N termini and with an amphipathic helix
      present within the N terminus. All these data suggest that the carrier encoded by
      thrE serves to export small molecules such as L-threonine and that the carrier is
      a prototype of a new translocator family. Homologues of ThrE are present in
      Mycobacterium tuberculosis and Streptomyces coelicolor.

PMID- 11514516
TI  - Noncatalytic docking domains of cellulosomes of anaerobic fungi.
AB  - A method is presented for the specific isolation of genes encoding cellulosome
      components from anaerobic fungi. The catalytic components of the cellulosome of
      anaerobic fungi typically contain, besides the catalytic domain, mostly two
      copies of a 40-amino-acid cysteine-rich, noncatalytic docking domain (NCDD)
      interspaced by short linkers. Degenerate primers were designed to anneal to the
      highly conserved region within the NCDDs of the monocentric fungus Piromyces sp.
      strain E2 and the polycentric fungus Orpinomyces sp. strain PC-2. Through PCR
      using cDNA from Orpinomyces sp. and genomic DNA from Piromyces sp. as templates,
      respectively, 9 and 19 PCR products were isolated encoding novel NCDD linker
      sequences. Screening of an Orpinomyces sp. cDNA library with four of these PCR
      products resulted in the isolation of new genes encoding cellulosome components.
      An alignment of the partial NCDD sequence information obtained and an alignment
      of database-accessible NCDD sequences, focusing on the number and position of
      cysteine residues, indicated the presence of three structural subfamilies within
      fungal NCDDs. Furthermore, evidence is presented that the NCDDs in CelC from the
      polycentric fungus Orpinomyces sp. strain PC-2 specifically recognize four
      proteins in a cellulosome preparation, indicating the presence of multiple
      scaffoldins.

PMID- 11514517
TI  - Mutational analysis of the Rhizobium lupini H13-3 and Sinorhizobium meliloti
      flagellin genes: importance of flagellin A for flagellar filament structure and
      transcriptional regulation.
AB  - Complex flagellar filaments are unusual in their fine structure composed of
      flagellin dimers, in their right-handed helicity, and in their rigidity, which
      prevents a switch of handedness. The complex filaments of Rhizobium lupini H13-3
      and those of Sinorhizobium meliloti are composed of three and four flagellin
      (Fla) subunits, respectively. The Fla-encoding genes, named flaA through flaD,
      are separately transcribed from sigma(28)-specific promoters. Mutational analysis
      of the fla genes revealed that, in both species, FlaA is the principal flagellin
      and that FlaB, FlaC, and FlaD are secondary. FlaA and at least one secondary Fla
      protein are required for assembling a functional flagellar filament. Western
      analysis revealed a ratio close to 1 of FlaA to the secondary Fla proteins (=
      FlaX) present in wild-type extracts, suggesting that the complex filament is
      assembled from FlaA-FlaX heterodimers. Whenever a given mutant combination of Fla
      prevented the assemblage of an intact filament, the biosynthesis of flagellin
      decreased dramatically. As shown in S. meliloti by reporter gene analysis, it is
      the transcription of flaA, but not of flaB, flaC, or flaD, that was down
      regulated by such abortive combinations of Fla proteins. This autoregulation of
      flaA is unusual. We propose that any combination of Fla subunits incapable of
      assembling an intact filament jams the flagellar export channel and thus prevents
      the escape of an (as yet unidentified) anti-sigma(28) factor that antagonizes the
      sigma(28)-dependent transcription of flaA.

PMID- 11514519
TI  - Hybrid protein between ribosomal protein S16 and RimM of Escherichia coli retains
      the ribosome maturation function of both proteins.
AB  - The RimM protein in Escherichia coli is associated with free 30S ribosomal
      subunits but not with 70S ribosomes and is important for efficient maturation of
      the 30S subunits. A mutant lacking RimM shows a sevenfold-reduced growth rate and
      a reduced translational efficiency. Here we show that a double alanine-for
      tyrosine substitution in RimM prevents it from associating with the 30S subunits
      and reduces the growth rate of E. coli approximately threefold. Several faster
      growing derivatives of the rimM amino acid substitution mutant were found that
      contain suppressor mutations which increased the amount of the RimM protein by
      two different mechanisms. Most of the suppressor mutations destabilized a
      secondary structure in the rimM mRNA, which previously was shown to decrease the
      synthesis of RimM by preventing the access of the ribosomes to the translation
      initiation region on the rimM mRNA. Three other independently isolated suppressor
      mutations created a fusion between rpsP, encoding the ribosomal protein S16, and
      rimM on the chromosome as a result of mutations in the rpsP stop codon preceding
      rimM. A severalfold-higher amount of the produced hybrid S16-RimM protein in the
      suppressor strains than of the native-sized RimM in the original substitution
      mutant seems to explain the suppression. The S16-RimM protein but not any native
      size ribosomal protein S16 was found both in free 30S ribosomal subunits and in
      translationally active 70S ribosomes of the suppressor strains. This suggests
      that the hybrid protein can substitute for S16, which is an essential protein
      probably because of its role in ribosome assembly. Thus, the S16-RimM hybrid
      protein seems capable of carrying out the important functions that native S16 and
      RimM have in ribosome biogenesis.

PMID- 11514518
TI  - The Brucella suis homologue of the Agrobacterium tumefaciens chromosomal
      virulence operon chvE is essential for sugar utilization but not for survival in
      macrophages.
AB  - Brucella strains possess an operon encoding type IV secretion machinery very
      similar to that coded by the Agrobacterium tumefaciens virB operon. Here we
      describe cloning of the Brucella suis homologue of the chvE-gguA-gguB operon of
      A. tumefaciens and characterize the sugar binding protein ChvE (78% identity),
      which in A. tumefaciens is involved in virulence gene expression. B. suis chvE is
      upstream of the putative sugar transporter-encoding genes gguA and gguB, also
      present in A. tumefaciens, but not adjacent to that of a LysR-type transcription
      regulator. Although results of Southern hybridization experiments suggested that
      the gene is present in all Brucella strains, the ChvE protein was detected only
      in B. suis and Brucella canis with A. tumefaciens ChvE-specific antisera,
      suggesting that chvE genes are differently expressed in different Brucella
      species. Analysis of cell growth of B. suis and of its chvE or gguA mutants in
      different media revealed that ChvE exhibited a sugar specificity similar to that
      of its A. tumefaciens homologue and that both ChvE and GguA were necessary for
      utilization of these sugars. Murine or human macrophage infections with B. suis
      chvE and gguA mutants resulted in multiplication similar to that of the wild-type
      strain, suggesting that virB expression was unaffected. These data indicate that
      the ChvE and GguA homologous proteins of B. suis are essential for the
      utilization of certain sugars but are not necessary for survival and replication
      inside macrophages.

PMID- 11514520
TI  - Functional analysis of OleY L-oleandrosyl 3-O-methyltransferase of the
      oleandomycin biosynthetic pathway in Streptomyces antibioticus.
AB  - Oleandomycin, a macrolide antibiotic produced by Streptomyces antibioticus,
      contains two sugars attached to the aglycon: L-oleandrose and D-desosamine. oleY
      codes for a methyltransferase involved in the biosynthesis of L-oleandrose. This
      gene was overexpressed in Escherichia coli to form inclusion bodies and in
      Streptomyces lividans, producing a soluble protein. S. lividans overexpressing
      oleY was used as a biotransformation host, and it converted the precursor L
      olivosyl-erythronolide B into its 3-O-methylated derivative, L-oleandrosyl
      erythronolide B. Two other monoglycosylated derivatives were also substrates for
      the OleY methyltransferase: L-rhamnosyl- and L-mycarosyl-erythronolide B. OleY
      methyltransferase was purified yielding a 43-kDa single band on sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis. The native enzyme showed a molecular
      mass of 87 kDa by gel filtration chromatography, indicating that the enzyme acts
      as a dimer. It showed a narrow pH range for optimal activity, and its activity
      was clearly stimulated by the presence of several divalent cations, being maximal
      with Co(2+). The S. antibioticus OleG2 glycosyltransferase is proposed to
      transfer L-olivose to the oleandolide aglycon, which is then converted into L
      oleandrose by the OleY methyltransferase. This represents an alternative route
      for L-oleandrose biosynthesis from that in the avermectin producer Streptomyces
      avermitilis, in which L-oleandrose is transferred to the aglycon by a
      glycosyltransferase.

PMID- 11514521
TI  - Membrane interaction of Escherichia coli hemolysin: flotation and insertion
      dependent labeling by phospholipid vesicles.
AB  - The 1,024-amino-acid acylated hemolysin of Escherichia coli subverts host cell
      functions and causes cell lysis. Both activities require insertion of the toxin
      into target mammalian cell membranes. To identify directly the principal toxin
      sequences dictating membrane binding and insertion, we assayed the lipid bilayer
      interaction of native protoxin, stably active toxin, and recombinant peptides.
      Binding was assessed by flotation of protein-liposome mixtures through density
      gradients, and insertion was assessed by labeling with a photoactivatable probe
      incorporated into the target lipid bilayer. Both the active acylated hemolysin
      and the inactive unacylated protoxin were able to bind and also insert. Ca(2+)
      binding, which is required for toxin activity, did not influence the in vitro
      interaction with liposomes. Three overlapping large peptides were expressed
      separately. A C-terminal peptide including residues 601 to 1024 did not interact
      in either assay. An internal peptide spanning residues 496 to 831, including the
      two acylation sites, bound to phospholipid vesicles and showed a low level of
      insertion-dependent labeling. In vitro acylation had no effect on the bilayer
      interaction of either this peptide or the full-length protoxin. An N-terminal
      peptide comprising residues 1 to 520 also bound to phospholipid vesicles and
      showed strong insertion-dependent labeling, ca. 5- to 25-fold that of the
      internal peptide. Generation of five smaller peptides from the N-terminal region
      identified the principal determinant of lipid insertion as the hydrophobic
      sequence encompassing residues 177 to 411, which is conserved among hemolysin
      related toxins.

PMID- 11514522
TI  - Hop resistance in the beer spoilage bacterium Lactobacillus brevis is mediated by
      the ATP-binding cassette multidrug transporter HorA.
AB  - Lactobacillus brevis is a major contaminant of spoiled beer. The organism can
      grow in beer in spite of the presence of antibacterial hop compounds that give
      the beer a bitter taste. The hop resistance in L. brevis is, at least in part,
      dependent on the expression of the horA gene. The deduced amino acid sequence of
      HorA is 53% identical to that of LmrA, an ATP-binding cassette multidrug
      transporter in Lactococcus lactis. To study the role of HorA in hop resistance,
      HorA was functionally expressed in L. lactis as a hexa-histidine-tagged protein
      using the nisin-controlled gene expression system. HorA expression increased the
      resistance of L. lactis to hop compounds and cytotoxic drugs. Drug transport
      studies with L. lactis cells and membrane vesicles and with proteoliposomes
      containing purified HorA protein identified HorA as a new member of the ABC
      family of multidrug transporters.

PMID- 11514523
TI  - Stringent response activates quorum sensing and modulates cell density-dependent
      gene expression in Pseudomonas aeruginosa.
AB  - During nutrient starvation, Escherichia coli elicits a stringent response
      involving the ribosome-associated protein RelA. Activation of RelA results in a
      global change in the cellular metabolism including enhanced expression of the
      stationary-phase sigma factor RpoS. In the human pathogen Pseudomonas aeruginosa,
      a complex quorum-sensing circuitry, linked to RpoS expression, is required for
      cell density-dependent production of many secreted virulence factors, including
      LasB elastase. Quorum sensing relies on the activation of specific
      transcriptional regulators (LasR and RhlR) by their corresponding autoinducers (3
      oxo-C(12)-homoserine lactone [HSL] and C(4)-HSL), which function as intercellular
      signals. We found that overexpression of relA activated the expression of rpoS in
      P. aeruginosa and led to premature, cell density-independent LasB elastase
      production. We therefore investigated the effects of the stringent response on
      quorum sensing. Both lasR and rhlR gene expression and autoinducer synthesis were
      prematurely activated during the stringent response induced by overexpression of
      relA. Premature expression of lasR and rhlR was also observed when relA was
      overexpressed in a PAO1 rpoS mutant. The stringent response induced by the amino
      acid analogue serine hydroxamate (SHX) also led to premature production of the 3
      oxo-C(12)-HSL autoinducer. This response to SHX was absent in a PAO1 relA mutant.
      These findings suggest that the stringent response can activate the two quorum
      sensing systems of P. aeruginosa independently of cell density.

PMID- 11514524
TI  - Biofilm formation by the fungal pathogen Candida albicans: development,
      architecture, and drug resistance.
AB  - Biofilms are a protected niche for microorganisms, where they are safe from
      antibiotic treatment and can create a source of persistent infection. Using two
      clinically relevant Candida albicans biofilm models formed on bioprosthetic
      materials, we demonstrated that biofilm formation proceeds through three distinct
      developmental phases. These growth phases transform adherent blastospores to well
      defined cellular communities encased in a polysaccharide matrix. Fluorescence and
      confocal scanning laser microscopy revealed that C. albicans biofilms have a
      highly heterogeneous architecture composed of cellular and noncellular elements.
      In both models, antifungal resistance of biofilm-grown cells increased in
      conjunction with biofilm formation. The expression of agglutinin-like (ALS)
      genes, which encode a family of proteins implicated in adhesion to host surfaces,
      was differentially regulated between planktonic and biofilm-grown cells. The
      ability of C. albicans to form biofilms contrasts sharply with that of
      Saccharomyces cerevisiae, which adhered to bioprosthetic surfaces but failed to
      form a mature biofilm. The studies described here form the basis for
      investigations into the molecular mechanisms of Candida biofilm biology and
      antifungal resistance and provide the means to design novel therapies for biofilm
      based infections.

PMID- 11514525
TI  - Alginate overproduction affects Pseudomonas aeruginosa biofilm structure and
      function.
AB  - During the course of chronic cystic fibrosis (CF) infections, Pseudomonas
      aeruginosa undergoes a conversion to a mucoid phenotype, which is characterized
      by overproduction of the exopolysaccharide alginate. Chronic P. aeruginosa
      infections involve surface-attached, highly antibiotic-resistant communities of
      microorganisms organized in biofilms. Although biofilm formation and the
      conversion to mucoidy are both important aspects of CF pathogenesis, the
      relationship between them is at the present unclear. In this study, we report
      that the overproduction of alginate affects biofilm development on an abiotic
      surface. Biofilms formed by an alginate-overproducing strain exhibit a highly
      structured architecture and are significantly more resistant to the antibiotic
      tobramycin than a biofilm formed by an isogenic nonmucoid strain. These results
      suggest that an important consequence of the conversion to mucoidy is an altered
      biofilm architecture that shows increasing resistance to antimicrobial
      treatments.

PMID- 11514526
TI  - Anatomical analysis of Saccharomyces cerevisiae stalk-like structures reveals
      spatial organization and cell specialization.
AB  - Recently we reported an unusual multicellular organization in yeast that we
      termed stalk-like structures. These structures are tall (0.5 to 3 cm long) and
      narrow (1 to 3 mm in diameter). They are formed in response to UV radiation of
      cultures spread on high agar concentrations. Here we present an anatomical
      analysis of the stalks. Microscopic inspection of cross sections taken from
      stalks revealed that stalks are composed of an inner core in which cells are
      dense and vital and a layer of cells (four to six rows) that surrounds the core.
      This outer layer is physically separated from the core and contains many dead
      cells. The outer layer may form a protective shell for the core cells. Through
      electron microscopy analysis we observed three types of cells within the stalk
      population: (i) cells containing many unusual vesicles, which might be undergoing
      some kind of cell death; (ii) cells containing spores (usually one or two spores
      only); and (iii) familiar rounded cells. We suggest that stalk cells are not only
      spatially organized but may undergo processes that induce a certain degree of
      cell specialization. We also show that high agar concentration alone, although
      not sufficient to induce stalk formation, induces dramatic changes in a colony's
      morphology. Most striking among the agar effects is the induction of growth into
      the agar, forming peg-like structures. Colonies grown on 4% agar or higher are
      reminiscent of stalks in some aspects. The agar concentration effects are
      mediated in part by the Ras pathway and are related to the invasive-growth
      phenomenon.

PMID- 11514527
TI  - Selection and characterization of Escherichia coli variants capable of growth on
      an otherwise toxic tryptophan analogue.
AB  - Escherichia coli isolates that were tolerant of incorporation of high proportions
      of 4-fluorotryptophan were evolved by serial growth. The resultant strain still
      preferred tryptophan for growth but showed improved growth relative to the
      parental strain on other tryptophan analogues. Evolved clones fully substituted
      fluorotryptophan for tryptophan in their proteomes within the limits of mass
      spectral and amino acid analyses. Of the genes sequenced, many genes were found
      to be unaltered in the evolved strain; however, three genes encoding enzymes
      involved in tryptophan uptake and utilization were altered: the aromatic amino
      acid permease (aroP) and tryptophanyl-tRNA synthetase (trpS) contained several
      amino acid substitutions, and the tyrosine repressor (tyrR) had a nonsense
      mutation. While kinetic analysis of the tryptophanyl-tRNA synthetase suggests
      discrimination against 4-fluorotryptophan, an analysis of the incorporation and
      growth patterns of the evolved bacteria suggest that other mutations also aid in
      the adaptation to the tryptophan analogue. These results suggest that the
      incorporation of unnatural amino acids into organismal proteomes may be possible
      but that extensive evolution may be required to reoptimize proteins and
      metabolism to accommodate such analogues.

PMID- 11514528
TI  - CotA of Bacillus subtilis is a copper-dependent laccase.
AB  - The spore coat protein CotA of Bacillus subtilis displays similarities with
      multicopper oxidases, including manganese oxidases and laccases. B. subtilis is
      able to oxidize manganese, but neither CotA nor other sporulation proteins are
      involved. We demonstrate that CotA is a laccase. Syringaldazine, a specific
      substrate of laccases, reacted with wild-type spores but not with DeltacotA
      spores. CotA may participate in the biosynthesis of the brown spore pigment,
      which appears to be a melanin-like product and to protect against UV light.

PMID- 11514529
TI  - Cohesin-dockerin interactions of cellulosomal subunits of Clostridium
      cellulovorans.
AB  - The cellulosome of Clostridium cellulovorans consists of three major subunits:
      CbpA, EngE, and ExgS. The C. cellulovorans scaffolding protein (CbpA) contains
      nine hydrophobic repeated domains (cohesins) for the binding of enzymatic
      subunits. Cohesin domains are quite homologous, but there are some questions
      regarding their binding specificity because some of the domains have regions of
      low-level sequence similarity. Two cohesins which exhibit 60% sequence similarity
      were investigated for their ability to bind cellulosomal enzymes. Cohesin 1
      (Coh1) was found to contain amino acid residues corresponding to amino acids 312
      to 453 of CbpA, which contains a total of 1,848 amino acid residues. Coh6 was
      determined to contain amino acid residues corresponding to residues 1113 to 1254
      of CbpA. By genetic construction, these two cohesins were each fused to MalE,
      producing MalE-Coh1 and MalE-Coh6. The abilities of two fusion proteins to bind
      to EngE, ExgS, and CbpA were compared. Although MalE-Coh6 could bind EngE and
      ExgS, little or no binding of the enzymatic subunits was observed with MalE-Coh1.
      Significantly, the abilities of the two fusion proteins to bind CbpA were
      similar. The binding of dockerin-containing enzymes to cohesin-containing
      proteins was suggested as a model for assembly of cellulosomes. In our
      examination of the role of dockerins, it was also shown that the binding of
      endoglucanase B (EngB) to CbpA was dependent on the presence of EngB's dockerin.
      These results suggest that different cohesins may function with differing
      efficiency and specificity, that cohesins may play some role in the formation of
      polycellulosomes through Coh-CbpA interactions, and that dockerins play an
      important role during the interaction of cellulosomal enzymes and cohesins
      present in CbpA.

PMID- 11514530
TI  - Distribution of the SsuDAT1I restriction-modification system among different
      serotypes of Streptococcus suis.
AB  - The SsuDAT1I restriction-modification (R-M) system, which contains two
      methyltransferases and two restriction endonucleases with recognition sequence 5'
      GATC-3', was first found in a field isolate of Streptococcus suis serotype 2.
      Isoschizomers of the R-M system were found in the same locus between purH and
      purD in a field isolate of serotype 1/2 and the reference strains of serotypes 3,
      7, 23, and 26 among 29 strains of different serotypes examined in this study. The
      R-M gene sequences in serotypes 1/2, 3, 7, and 23 were very similar to those of
      SsuDAT1I, whereas those in serotype 26 were less similar. These results indicate
      intraspecies recombination among them and genetic divergence through their
      evolution.

PMID- 11514531
TI  - Directed evolution of biphenyl dioxygenase: emergence of enhanced degradation
      capacity for benzene, toluene, and alkylbenzenes.
AB  - Biphenyl dioxygenase (Bph Dox) catalyzes the initial oxygenation of biphenyl and
      related compounds. Bph Dox is a multicomponent enzyme in which a large subunit
      (encoded by the bphA1 gene) is significantly responsible for substrate
      specificity. By using the process of DNA shuffling of bphA1 of Pseudomonas
      pseudoalcaligenes KF707 and Burkholderia cepacia LB400, a number of evolved Bph
      Dox enzymes were created. Among them, an Escherichia coli clone expressing
      chimeric Bph Dox exhibited extremely enhanced benzene-, toluene-, and
      alkylbenzene-degrading abilities. In this evolved BphA1, four amino acids (H255Q,
      V258I, G268A, and F277Y) were changed from the KF707 enzyme to those of the LB400
      enzyme. Subsequent site-directed mutagenesis allowed us to determine the amino
      acids responsible for the degradation of monocyclic aromatic hydrocarbons.

PMID- 11514532
TI  - Involvement of sigma(S) in starvation-induced transposition of Pseudomonas putida
      transposon Tn4652.
AB  - Transpositional activity of mobile elements can be induced by different
      environmental stresses. Here, we present evidence that transposition of Tn4652 is
      elevated in stationary-phase Pseudomonas putida and suppressed in an isogenic
      sigma(S)-defective strain. We demonstrate that transcription from the Tn4652
      transposase promoter is controlled by the stationary-phase-specific sigma factor
      sigma(S). To our knowledge, this is the first example of direct stationary-phase
      specific regulation of a mobile element transposase. Data presented in this
      report support the idea that activation of transposition under stressful
      conditions could be an inducible process.

PMID- 11514533
TI  - Polymer stability plays an important role in the positional regulation of FtsZ.
AB  - We conducted a series of experiments examining the effect of polymer stability on
      FtsZ localization dynamics in Bacillus subtilis. A loss-of-function mutation in
      ezrA, a putative polymer-destabilizing factor, suppresses the defects in FtsZ
      polymer stability associated with minCD overexpression. In addition, a mutation
      that is predicted to stabilize the FtsZ polymer leads to the formation of polar
      FtsZ rings. These data support the hypothesis that carefully balanced polymer
      stability is important for the assembly and localization of FtsZ during the
      bacterial cell cycle.

PMID- 11514534
TI  - Recombinational transfer of 100-kilobase genomic DNA to plasmid in Bacillus
      subtilis 168.
AB  - Transformation of Bacillus subtilis by a plasmid requires a circular multimeric
      form. In contrast, linearized plasmids can be circularized only when homologous
      sequences are present in the host genome. A recombinational transfer system was
      constructed with this intrinsic B. subtilis recombinational repair pathway. The
      vector, pGETS103, a derivative of the theta-type replicating plasmid pTB19 of
      thermophilic Bacillus, had the full length of Escherichia coli plasmid pBR322. A
      multimeric form of pGETS103 yielded tetracycline-resistant transformants of B.
      subtilis. In contrast, linearized pGETS103 gave tetracycline-resistant
      transformants only when the recipient strain had the pBR322 sequence in the
      genome. The efficiency and fidelity of the recombinational transfer of DNAs of up
      to 90 kb are demonstrated.

PMID- 11514535
TI  - Autophosphorylation of archaeal Cdc6 homologues is regulated by DNA.
AB  - The initiator protein Cdc6 (Cdc18 in fission yeast) plays an essential role in
      the initiation of eukaryotic DNA replication. In yeast the protein is expressed
      before initiation of DNA replication and is thought to be essential for loading
      of the helicase onto origin DNA. The biochemical properties of the protein,
      however, are largely unknown. Using three archaeal homologues of Cdc6, it was
      found that the proteins are autophosphorylated on Ser residues. The winged-helix
      domain at the C terminus of Cdc6 interacts with DNA, which apparently regulates
      the autophosphorylation reaction. Yeast Cdc18 was also found to
      autophosphorylate, suggesting that this function of Cdc6 may play a widely
      conserved and essential role in replication initiation.

PMID- 11514536
TI  - YY1 is a positive regulator of transcription of the Col1a1 gene.
AB  - Both cell-specific and ubiquitous transcription factors in fibroblasts have been
      identified as critical for expression of the Col1a1 gene, which encodes the
      alpha1 chain of type I collagen. Here, we report that Yin Yang 1 (YY1) binds to
      the Col1a1 promoter immediately upstream of the TATA box, and we examine the
      functional implications of YY1 binding for regulation of Col1a1 gene expression
      in BALBc/3T3 fibroblasts. The Col1a1 promoter region spanning base pairs (bp) -56
      to -9 bound purified recombinant YY1 and the corresponding binding activity in
      nuclear extracts was supershifted using a YY1-specific antibody. Mutation of the
      TATA box to TgTA enhanced YY1 complex formation. Mutation analysis revealed two
      YY1 core binding sites at -40/-37 bp (YY1A) and, on the reverse strand, at -32/
      29 bp (YY1B) immediately adjacent to the TATA box. In transfections using Col1a1
      luciferase constructs, mutation of YY1A decreased activity completely (wild-type
      p350 (p350wt), -222/+113 bp) or partially (p130wt, -84 bp/+13 bp), whereas
      mutation of YY1B blocked the expression of both promoter constructs.
      Cotransfection with pCMV-YY1 increased p350wt and p130wt activities by as much as
      10-fold, whereas antisense YY1 decreased constitutive expression and blocked the
      increased activity due to pCMV-YY1 overexpression. The mTgTA constructs were
      devoid of activity, arguing for a requirement for cognate binding of the TATA box
      binding protein (TBP). Electrophoretic mobility shift assays performed under
      conditions permitting TBP binding showed that recombinant TBP/TFIID and YY1 could
      bind to the -56/-9 bp fragment and that YY1B was the preferred site for YY1
      binding. Our results indicate that YY1 binds to the Col1a1 proximal promoter and
      functions as a positive regulator of constitutive activity in fibroblasts.
      Although YY1 is not sufficient for transcriptional initiation, it is a required
      component of the transcription machinery in this promoter.

PMID- 11514537
TI  - Downregulation of small GTPase Rab7 impairs osteoclast polarization and bone
      resorption.
AB  - During skeletal growth and remodeling the mineralized bone matrix is resorbed by
      osteoclasts through the constant secretion of protons and proteases to the bone
      surface. This relies on the formation of specialized plasma membrane domains, the
      sealing zone and the ruffled border, and vectorial transportation of
      intracellular vesicles in bone-resorbing osteoclasts. Here we show that Rab7, a
      small GTPase that is associated with late endosomes, is highly expressed and is
      predominantly localized at the ruffled border in bone-resorbing osteoclasts. The
      decreased expression of Rab7 in cultured osteoclasts by antisense
      oligodeoxynucleotides disrupted the polarization of the osteoclasts and the
      targeting of vesicles to the ruffled border. These impairments caused a
      significant inhibition of bone resorption in vitro. The results indicate that the
      late endocytotic pathway is involved in the osteoclast polarization and bone
      resorption and underscore the importance of Rab7 in osteoclast function.

PMID- 11514538
TI  - Vascular endothelial growth factor 165 (VEGF(165)) activities are inhibited by
      carboxymethyl benzylamide dextran that competes for heparin binding to VEGF(165)
      and VEGF(165).KDR Complexes.
AB  - We have previously shown that carboxymethyl dextran benzylamide (CMDB7), a
      heparin-like molecule, inhibits the growth of tumors xenografted in nude mice,
      angiogenesis, and metastasis by altering the binding of angiogenic growth
      factors, including platelet-derived growth factor, transforming growth factor
      beta, and fibroblast growth factor 2, to their specific receptors. In this study,
      we explore the effect of CMDB7 on the most specific angiogenic growth factor,
      vascular endothelial growth factor 165 (VEGF(165)). We demonstrate here that
      CMDB7 inhibits the mitogenic effect of VEGF(165) on human umbilical vein
      endothelial cells (HUV-ECs) by preventing the VEGF(165)-induced VEGF receptor-2
      (KDR) autophosphorylation and consequently a specific intracellular signaling. In
      competition experiments, the binding of (125)I-VEGF(165) to HUV-ECs is inhibited
      by CMDB7 with an IC(50) of 2 microm. Accordingly, CMDB7 inhibits the cross
      linking of (125)I-VEGF(165) to the surface of HUV-ECs, causing the disappearance
      of both labeled complexes, 170-180 and 240-250 kDa. We show that CMDB7 increases
      the electrophoretic mobility of VEGF(165), thus evidencing formation of a stable
      complex with this factor. Moreover, CMDB7 reduces the (125)I-VEGF(165) binding to
      coated heparin-albumin and prevents a heparin-induced increase in iodinated
      VEGF(165) binding to soluble (125)I-KDR-Fc chimera. Concerning KDR, CMDB7 has no
      effect on (125)I-KDR-Fc electrophoretic migration and does not affect labeled KDR
      Fc binding to coated heparin-albumin. In the presence of VEGF(165), (125)I-KDR-Fc
      binding to heparin is enhanced, and under these conditions, CMDB7 interferes with
      KDR binding. These data indicate that CMDB7 effectively inhibits the VEGF(165)
      activities by interfering with heparin binding to VEGF(165) and VEGF(165).KDR
      complexes but not by direct interactions with KDR.

PMID- 11514539
TI  - Specific interaction of angiostatin with integrin alpha(v)beta(3) in endothelial
      cells.
AB  - Angiostatin, the N-terminal four kringles (K1-4) of plasminogen, blocks tumor
      mediated angiogenesis and has great therapeutic potential. However, angiostatin's
      mechanism of anti-angiogenic action is unclear. We found that bovine arterial
      endothelial (BAE) cells adhere to angiostatin in an integrin-dependent manner and
      that integrins alpha(v)beta(3), alpha(9)beta(1), and to a lesser extent
      alpha(4)beta(1), specifically bind to angiostatin. alpha(v)beta(3) is a
      predominant receptor for angiostatin on BAE cells, since a function-blocking
      antibody to alpha(v)beta(3) effectively blocks adhesion of BAE cells to
      angiostatin, but an antibody to alpha(9)beta(1) does not. epsilon-Aminocaproic
      acid, a Lys analogue, effectively blocks angiostatin binding to BAE cells,
      indicating that an unoccupied Lys-binding site of the kringles may be required
      for integrin binding. It is known that other plasminogen fragments containing
      three or five kringles (K1-3 or K1-5) have an anti-angiogenic effect, but
      plasminogen itself does not. We found that K1-3 and K1-5 bind to alpha(v)beta(3),
      but plasminogen does not. These results suggest that the anti-angiogenic action
      of angiostatin may be mediated via interaction with alpha(v)beta(3). Angiostatin
      binding to alpha(v)beta(3) does not strongly induce stress-fiber formation,
      suggesting that angiostatin may prevent angiogenesis by perturbing the
      alpha(v)beta(3)-mediated signal transduction that may be necessary for
      angiogenesis.

PMID- 11514540
TI  - Inhibition of Polo-like kinase-1 by DNA damage occurs in an ATM- or ATR-dependent
      fashion.
AB  - Polo-like kinases play multiple roles in different phases of mitosis. We have
      recently shown that the mammalian polo-like kinase, Plk1, is inhibited in
      response to DNA damage and that this inhibition may lead to cell cycle arrests at
      multiple points in mitosis. Here we have investigated the role of the checkpoint
      kinases ATM (ataxia telangiectasia mutated) and ATR (ATM- and Rad3-related) in
      DNA damage-induced inhibition of Plk1. We show that inhibition of Plk1 kinase
      activity is efficiently blocked by the radio-sensitizing agent caffeine. Using
      ATM(-/-) cells we show that under certain circumstances, inhibition of Plk1 by
      DNA-damaging agents critically depends on ATM. In addition, we show that UV
      radiation also causes inhibition of Plk1, and we present evidence that this
      inhibition is mediated by ATR. Taken together, our data demonstrate that ATM and
      ATR can regulate Plk1 kinase activity in response to a variety of DNA-damaging
      agents.

PMID- 11514541
TI  - A direct interaction between oncogenic Ha-Ras and phosphatidylinositol 3-kinase
      is not required for Ha-Ras-dependent transformation of epithelial cells.
AB  - Cells expressing oncogenic Ras proteins transmit a complex set of signals that
      ultimately result in constitutive activation of signaling molecules, culminating
      in unregulated cellular function. Although the role of oncogenic Ras in a variety
      of cellular responses including transformation, cell survival, differentiation,
      and migration is well documented, the direct Ras/effector interactions that
      contribute to the different Ras biological end points have not been as clearly
      defined. Observations by other groups in which Ras-dependent transformation can
      be blocked by expression of either dominant negative forms of
      Phosphatidylinositol (PI) 3-kinase or PTEN, a 3-phosphoinositide-specific
      phosphatase, support an essential role for PI 3-kinase and its lipid products in
      the transformation process. These observations coupled with the in vitro
      observations that the catalytic subunits of PI 3-kinase, the p110 isoforms, bind
      directly to Ras-GTP foster the implication that a direct interaction between an
      oncogenic Ras protein and PI 3-kinase are causal in the oncogenicity of mutant
      Ras proteins. Using an activated Ha-Ras protein (Y64G/Y71G/F156L) that fails to
      interact with PI 3-kinase, we demonstrate that oncogenic Ha-Ras does not require
      a direct interaction with PI 3-kinase to support anchorage-independent growth of
      IEC-6 epithelial cells. We do find, however, that IEC-6 cells expressing an
      oncogenic Ha-Ras protein that no longer binds PI 3-kinase are greatly impaired in
      their ability to migrate toward fibronectin.

PMID- 11514542
TI  - Interferon-kappa, a novel type I interferon expressed in human keratinocytes.
AB  - High throughput cDNA sequencing has led to the identification of interferon
      kappa, a novel subclass of type I interferon that displays approximately 30%
      homology to other family members. Interferon-kappa consists of 207 amino acids,
      including a 27-amino acid signal peptide and a series of cysteines conserved in
      type I interferons. The gene encoding interferon-kappa is located on the short
      arm of chromosome 9 adjacent to the type I interferon gene cluster and is
      selectively expressed in epidermal keratinocytes. Expression of interferon-kappa
      is significantly enhanced in keratinocytes upon viral infection, upon exposure to
      double-stranded RNA, or upon treatment with either interferon-gamma or interferon
      beta. Administration of interferon-kappa recombinant protein imparts cellular
      protection against viral infection in a species-specific manner. Interferon-kappa
      activates the interferon-stimulated response element signaling pathway and a
      panel of genes similar to those regulated by other type I interferons including
      anti-viral mediators and transcriptional regulators. An antibody that neutralizes
      the type I interferon receptor completely blocks interferon-kappa signaling,
      demonstrating that interferon-kappa utilizes the same receptor as other type I
      interferons. Interferon-kappa therefore defines a novel subclass of type I
      interferon that is expressed in keratinocytes and expands the repertoire of known
      proteins mediating host defense.

PMID- 11514543
TI  - The cell adhesion domain of type XVII collagen promotes integrin-mediated cell
      spreading by a novel mechanism.
AB  - Type XVII collagen (BP180) is a keratinocyte transmembrane protein that exists as
      the full-length protein in hemidesmosomes and as a 120-kDa shed ectodomain in the
      extracellular matrix. The largest collagenous domain of type XVII collagen,
      COL15, has been described previously as a cell adhesion domain (Tasanen, K.,
      Eble, J. A., Aumailley, M., Schumann, H., Baetge, J, Tu, H., Bruckner, P., and
      Bruckner-Tuderman, L. (2000) J. Biol. Chem. 275, 3093-3099). In the present work,
      the integrin binding of triple helical, human recombinant COL15 was tested. Solid
      phase binding assays using recombinant integrin alpha(1)I, alpha(2)I, and
      alpha(10)I domains and cell spreading assays with alpha(1)beta(1)- and
      alpha(2)beta(1)-expressing Chinese hamster ovary cells showed that, unlike other
      collagens, COL15 was not recognized by the collagen receptors. Denaturation of
      the COL15 domain increased the spreading of human HaCaT keratinocytes, which
      could migrate on the denatured COL15 domain as effectively as on fibronectin.
      Spreading of HaCaT cells on the COL15 domain was mediated by alpha(5)beta(1) and
      alpha(V)beta(1) integrins, and it could be blocked by RGD peptides. The collagen
      alpha-chains in the COL15 domain do not contain RGD motifs but, instead, contain
      12 closely related KGD motifs, four in each of the three alpha-chains. Twenty-two
      overlapping, synthetic peptides corresponding to the entire COL15 domain were
      tested; three peptides, all containing the KGD motif, inhibited the spreading of
      HaCaT cells on denatured COL15 domain. Furthermore, this effect was lost by
      mutation from D to E (KGE instead of KGD). We suggest that the COL15 domain of
      type XVII collagen represents a specific collagenous structure, unable to
      interact with the cellular receptors for other collagens. After being shed from
      the cell surface, it may support keratinocyte spreading and migration.

PMID- 11514544
TI  - Requirement of two NFATc4 transactivation domains for CBP potentiation.
AB  - Recruitment of the coactivator CREB-binding protein (CBP) to transcription
      factors is important for gene expression. Various regions of CBP such as the KIX
      and CH3 domains have been shown to interact with numerous transcription factors.
      The NFAT group of transcription factors is involved in multiple biological
      processes. NFATc4/NFAT3 has been proposed to play an important role in heart
      hypertrophy, adipocyte differentiation, and learning and memory. We demonstrate
      here that two transactivation domains, located at the NH(2) and COOH termini of
      NFATc4, are critical for interacting with CBP. Each transactivation domain
      interacts with a distinct region of the CBP protein (the KIX and CH3 domains).
      Binding of CBP potentiates NFATc4-mediated transcription activity. Both
      transactivation domains of NFATc4 are required for CBP function. Removal of
      either NFATc4 transactivation domain abolishes CBP potentiation. Conversely,
      mutation of the KIX or CH3 domain prevents CBP-mediated potentiation of NFATc4
      transcription activation. These data demonstrate that formation of a functional
      NFATc4.CBP transcription complex requires interactions at two distinct sites.

PMID- 11514545
TI  - Altered fine structures of corneal and skeletal keratan sulfate and
      chondroitin/dermatan sulfate in macular corneal dystrophy.
AB  - The content and fine structure of keratan and chondroitin/dermatan sulfate in
      normal human corneas and corneas affected by macular corneal dystrophies (MCD)
      types I and II were examined by fluorophore-assisted carbohydrate
      electrophoresis. Normal tissues (n = 11) contained 15 microg of keratan sulfate
      and 8 microg of chondroitin/dermatan sulfate per mg dry weight. Keratan sulfates
      consisted of approximately 4% unsulfated, 42% monosulfated, and 54% disulfated
      disaccharides with number of average chain lengths of approximately 14
      disaccharides. Chondroitin/dermatan sulfates were significantly longer,
      approximately 40 disaccharides per chain, and consisted of approximately 64%
      unsulfated, 28% 4-sulfated, and 8% 6-sulfated disaccharides. The fine structural
      parameters were altered in all diseased tissues. Keratan sulfate chain size was
      reduced to 3-4 disaccharides; chain sulfation was absent in MCD type I corneas
      and cartilages, and sulfation of both GlcNAc and Gal was significantly reduced in
      MCD type II. Chondroitin/dermatan sulfate chain sizes were also decreased in all
      diseased corneas to approximately 15 disaccharides, and the contents of 4- and 6
      sulfated disaccharides were proportionally increased. Tissue concentrations
      (nanomole of chains per mg dry weight) of all glycosaminoglycan types were
      affected in the disease types. Keratan sulfate chain concentrations were reduced
      by approximately 24 and approximately 75% in type I corneas and cartilages,
      respectively, and by approximately 50% in type II corneas. Conversely,
      chondroitin/dermatan sulfate chain concentrations were increased by 60-70% in
      types I and II corneas. Such changes imply a modified tissue content of
      individual proteoglycans and/or an altered efficiency of chain substitution on
      the core proteins. Together with the finding that hyaluronan, not normally
      present in healthy adult corneas, was also detected in both disease subtypes, the
      data support the conclusion that a wide range of keratocyte-specific proteoglycan
      and glycosaminoglycan remodeling processes are activated during degeneration of
      the stromal matrix in the macular corneal dystrophies.

PMID- 11514546
TI  - The von Hippel-Lindau gene product inhibits renal cell apoptosis via Bcl-2
      dependent pathways.
AB  - Previous studies have reported a protective role for the von Hippel-Lindau (VHL)
      gene products against pro-apoptotic cellular stresses, but the mechanisms remain
      unclear. In this study, we examined the role of VHL in renal cells subjected to
      chemical hypoxia, using four VHL-negative and two VHL-positive cell lines. VHL
      negative renal carcinoma cells underwent apoptosis following chemical hypoxia
      (short-term glucose deprivation and antimycin treatment), as evidenced by
      morphologic changes and internucleosomal DNA cleavage. Reintroduction of VHL
      expression prevented this apoptosis. VHL-negative cells displayed a significant
      (greater than 5-fold) activation of caspase 9 and release of cytochrome c into
      the cytosol following chemical hypoxia. In contrast, VHL-positive cells showed
      minimal caspase 9 activation, and absence of cytochrome c release under the same
      conditions. Caspase 8 was only minimally activated in both VHL-negative and 
      positive cells. In addition, VHL-positive cells displayed a striking up
      regulation of Bcl-2 expression (5-fold) following chemical hypoxia. Antisense
      oligonucleotides to Bcl-2 significantly down-regulated Bcl-2 protein expression
      in VHL-positive cells and rendered them sensitive to apoptosis. Overexpression of
      Bcl-2 in VHL-negative cells conferred resistance to apoptosis. Our results
      suggest that VHL protects renal cells from apoptosis via Bcl-2-dependent
      pathways.

PMID- 11514547
TI  - Functional properties of Cav1.3 (alpha1D) L-type Ca2+ channel splice variants
      expressed by rat brain and neuroendocrine GH3 cells.
AB  - Ca(2+) enters pituitary and pancreatic neuroendocrine cells through
      dihydropyridine-sensitive channels triggering hormone release. Inhibitory
      metabotropic receptors reduce Ca(2+) entry through activation of pertussis toxin
      sensitive G proteins leading to activation of K(+) channels and voltage-sensitive
      inhibition of L-type channel activity. Despite the cloning and functional
      expression of several Ca(2+) channels, those involved in regulating hormone
      release remain unknown. Using reverse transcription-polymerase chain reaction we
      identified mRNAs encoding three alpha(1) (alpha(1A), alpha(1C), and alpha(1D)),
      four beta, and one alpha(2)-delta subunit in rat pituitary GH(3) cells; alpha(1B)
      and alpha(1S) transcripts were absent. GH(3) cells express multiple alternatively
      spliced alpha(1D) mRNAs. Many of the alpha(1D) transcript variants encode "short"
      alpha(1D) (alpha(1D-S)) subunits, which have a QXXER amino acid sequence at their
      C termini, a motif found in all other alpha(1) subunits that couple to opioid
      receptors. The other splice variants identified terminate with a longer C
      terminus that lacks the QXXER motif (alpha(1D-L)). We cloned and expressed the
      predominant alpha(1D-S) transcript variants in rat brain and GH(3) cells and
      their alpha(lD-L) counterpart in GH(3) cells. Unlike alpha(1A) channels,
      alpha(1D) channels exhibited current-voltage relationships similar to those of
      native GH(3) cell Ca(2+) channels, but lacked voltage-dependent G protein
      coupling. Our data demonstrate that alternatively spliced alpha(1D) transcripts
      form functional Ca(2+) channels that exhibit voltage-dependent, G protein
      independent facilitation. Furthermore, the QXXER motif, located on the C terminus
      of alpha(1D-S) subunit, is not sufficient to confer sensitivity to inhibitory G
      proteins.

PMID- 11514548
TI  - How transcriptional activators bind target proteins.
AB  - The product of the proto-oncogene c-myc influences many cellular processes
      through the regulation of specific target genes. Through its transactivation
      domain (TAD), c-Myc protein interacts with several transcription factors,
      including TATA-binding protein (TBP). We present data that suggest that in
      contrast to some other transcriptional activators, an extended length of the c
      Myc TAD is required for its binding to TBP. Our data also show that this
      interaction is a multistep process, in which a rapidly forming low affinity
      complex slowly converts to a more stable form. The initial complex formation
      results from ionic or polar interactions, whereas the slow conversion to a more
      stable form is hydrophobic in nature. Based on our results, we suggest two
      alternative models for activation domain/target protein interactions, which
      together provide a single universal paradigm for understanding activator-target
      factor interactions.

PMID- 11514549
TI  - Analysis of small GTPase signaling pathways using p21-activated kinase mutants
      that selectively couple to Cdc42.
AB  - p21-activated kinase 1 (Pak1) is an effector for the small GTPases Cdc42 and Rac.
      Because Pak1 binds to and is activated by both these GTPases, it has been
      difficult to precisely delineate the signaling pathways that link extracellular
      stimuli to Pak1 activation. To separate activation of Pak1 by Cdc42 versus
      activation by Rac, we devised a genetic screen in yeast that enabled us to create
      and identify Pak1 mutants that selectively couple to Cdc42 but not Rac1. We
      recovered several such Pak1 mutants and found that the residues most often
      affected lie within the p21 binding domain, a region previously known to mediate
      Pak1 binding to GTPases, but that several mutations also map outside the borders
      of the p21 binding domain. Pak1 mutants that associate with Cdc42 but not Rac1
      were also activated by Cdc42 but not Rac1. In rat 3Y1 cells expressing oncogenic
      Ha-Ras, the Pak1 mutants defective in Rac1 binding are not activated, suggesting
      that Ras signals through a GTPase other than Cdc42 to activate Pakl. Similar
      results were obtained when epidermal growth factor was used to activate Pak1.
      However, Pak1 mutants that are unable to bind Rac are nonetheless well activated
      by calf serum, implying that this stimulus may induce Pak activation independent
      of Rac.

PMID- 11514550
TI  - Cloning and expression of a fungal L-arabinitol 4-dehydrogenase gene.
AB  - L-Arabinitol 4-dehydrogenase (EC ) was purified from the filamentous fungus
      Trichoderma reesei (Hypocrea jecorina). It is an enzyme in the L-arabinose
      catabolic pathway of fungi catalyzing the reaction from L-arabinitol to L
      xylulose. The amino acid sequence of peptide fragments was determined and used to
      identify the corresponding gene. We named the gene lad1. It is not constitutively
      expressed. In a Northern analysis we found it only after growth on L-arabinose.
      The gene was cloned and overexpressed in Saccharomyces cerevisiae, and the enzyme
      activity was confirmed in a cell extract. The enzyme consists of 377 amino acids
      and has a calculated molecular mass of 39,822 Da. It belongs to the family of
      zinc-binding dehydrogenases and has some amino acid sequence similarity to
      sorbitol dehydrogenases. It shows activity toward L-arabinitol, adonitol
      (ribitol), and xylitol with K(m) values of about 40 mM toward L-arabinitol and
      adonitol and about 180 mM toward xylitol. No activity was observed with D
      sorbitol, D-arabinitol, and D-mannitol. NAD is the required cofactor with a K(m)
      of 180 microM. No activity was observed with NADP.

PMID- 11514551
TI  - Baseline cytosolic Ca2+ oscillations derived from a non-endoplasmic reticulum
      Ca2+ store.
AB  - Cytosolic Ca(2+) oscillations can be due to cycles of release and re-uptake of
      internally stored Ca(2+). To investigate the nature of these Ca(2+) stores, we
      expressed the Pmr1 Ca(2+) pump of Caenorhabditis elegans in COS-1 cells and
      pretreated the cells with thapsigargin to prevent Ca(2+) uptake by the
      sarco(endo)plasmic reticulum Ca(2+)-ATPase. Pmr1 co-localized with the Golgi
      specific 58K protein and was targeted to a Ca(2+) store that was less leaky for
      Ca(2+) than the endoplasmic reticulum and whose inositol trisphosphate receptors
      were less sensitive to inositol trisphosphate and ATP than those in the
      endoplasmic reticulum. ATP-stimulated Pmr1-overexpressing cells responded after a
      latency to extracellular Ca(2+) with a regenerative Ca(2+) signal, which could be
      prevented by caffeine. They also produced very stable ilimaquinone-sensitive
      baseline Ca(2+) spikes, even in the presence of thapsigargin. Such responses
      never occurred in non-transfected cells or in cells that overexpressed the type-1
      sarco(endo)plasmic reticulum Ca(2+)-ATPase. Abortive Ca(2+) spikes also occurred
      in histamine-stimulated untransfected HeLa cells pretreated with thapsigargin,
      and they too were inhibited by ilimaquinone. We conclude that the Pmr1-induced
      Ca(2+) store, which probably corresponds to the Golgi compartment, can play a
      crucial role in setting up baseline Ca(2+) spiking.

PMID- 11514552
TI  - Regulation of Drosophila TRPL channels by immunophilin FKBP59.
AB  - Transient receptor potential and transient receptor potential-like (TRPL) are
      Ca(2+)-permeable cation channels found in Drosophila photoreceptor cells
      associated with large multimeric signaling complexes held together by the
      scaffolding protein, INAD. To identify novel proteins involved in channel
      regulation, Drosophila INAD was used as bait in a yeast two-hybrid screen of a
      Drosophila head cDNA library. Sequence analysis of one identified clone showed it
      to be identical to the Drosophila homolog of human FK506-binding protein, FKBP52
      (previously known as FKBP59). To determine the function of dFKBP59, TRPL channels
      and dFKBP59 were co-expressed in Sf9 cells. Expression of dFKBP59 produced an
      inhibition of Ca(2+) influx via TRPL in fura-2 assays. Likewise, purified
      recombinant dFKBP59 produced a graded inhibition of TRPL single channel activity
      in excised inside-out patches when added to the cytoplasmic membrane surface.
      Immunoprecipitations from Sf9 cell lysates using recombinant tagged dFKBP59 and
      TRPL showed that these proteins directly interact with each other and with INAD.
      Addition of FK506 prior to immunoprecipitation resulted in a temperature
      dependent dissociation of dFKBP59 and TRPL. Immunoprecipitations from Drosophila
      S2 cells and from fly head lysates demonstrated that dFKBP59, but not dFKBP12,
      interacts with TRPL in vivo. Likewise, INAD immunoprecipitates with dFKBP59 from
      S2 cell and head lysates. Immunocytochemical evaluation of thin sections of fly
      heads revealed specific FKBP immunoreactivity associated with the eye. Site
      directed mutagenesis showed that mutations of P702Q or P709Q in the highly
      conserved TRPL sequence (701)LPPPFNVLP(709) eliminated interaction of the TRPL
      with dFKBP59. These results provide strong support for the hypothesis that
      immunophilin dFKBP59 is part of the TRPL-INAD signaling complex and plays an
      important role in modulation of channel activity via interaction with conserved
      leucyl-prolyl dipeptides located near the cytoplasmic mouth of the channel.

PMID- 11514553
TI  - A molecular switch for specific stimulation of the BKCa channel by cGMP and cAMP
      kinase.
AB  - The cGMP and the cAMP pathways control smooth muscle tone by regulation of BK(Ca)
      (BK) channel activity. BK channels show considerable diversity and plasticity in
      their regulation by cyclic nucleotide-dependent protein kinases. The underlying
      molecular mechanisms are unclear but may involve expression of splice variants of
      the BK channel alpha subunit. Three isoforms, BK(A), BK(B), and BK(C), which were
      cloned from tracheal smooth muscle, differed only in their C terminus. When
      expressed in HEK293 cells, cGMP kinase (cGK) but not cAMP kinase (cAK) stimulated
      the activity of BK(A) and BK(B) by shifting the voltage dependence of the channel
      to more negative potentials. In contrast, BK(C) was exclusively stimulated by
      cAK. BK(C) lacks a C-terminal tandem phosphorylation motif for protein kinase C
      (PKC) with Ser(1151) and Ser(1154). Mutation of this motif in BK(A) switched
      channel regulation from cGK to cAK. Furthermore, inhibition of PKC in excised
      patches from cells expressing BK(A) abolished the stimulatory effect of cGK but
      allowed channel stimulation by cAK. cAK and cGK phosphorylated the channel at
      different sites. Thus, phosphorylation/dephosphorylation by PKC determines
      whether the BK channel is stimulated by cGK or cAK. The molecular mechanisms may
      be relevant for smooth muscle relaxation by cAMP and cGMP.

PMID- 11514554
TI  - The transcription factor SOX9 regulates cell cycle and differentiation genes in
      chondrocytic CFK2 cells.
AB  - SOX9 is a transcription factor that is essential for chondrocyte differentiation
      and cartilage formation. We stably overexpressed SOX9 cDNA in the rat
      chondrocytic cell line CFK2. Compared with the vector control, a greater
      proportion of SOX9-transfected cells accumulated in the G0/G1 phase. This was
      associated with an increase in mRNA and protein expression of p21(cip1), an
      inhibitor of cyclin-dependent kinase activity. SOX9 enhanced p21(cip1) promoter
      activity in a luciferase reporter assay. CFK2 cells overexpressing SOX9 became
      more elongated and adhesive and demonstrated a shift in cytoplasmic F-actin
      distribution. N-cadherin mRNA levels were elevated in the SOX9-transfected cells,
      and SOX9 enhanced N-cadherin promoter activity. By electrophoretic mobility shift
      assay, nuclear extracts of SOX9-transfected CFK2 cells specifically bound an
      oligonucleotide comprising an N-cadherin promoter region containing a consensus
      SOX9-binding motif. The transcriptional activity of SOX9 depended upon nuclear
      localization signals required for SOX9 nuclear entry. Differentiation of
      transfected CFK2 cells was accelerated as evidenced by more rapid accumulation of
      alkaline phosphatase activity, increased production of proteoglycans, and
      increased calcium accumulation, and this was associated with decreased ERK1
      expression. These studies demonstrate that SOX9 alters the rate of cell cycle
      progression of chondrocytes and their differentiation by enhancing or inhibiting
      the expression of selected genes, including p21(cip1) and ERK1, and that N
      cadherin is an additional direct target of this transcriptional regulator.

PMID- 11514555
TI  - The plasma membrane calcium pump displays memory of past calcium spikes.
      Differences between isoforms 2b and 4b.
AB  - To understand how the plasma membrane Ca(2+) pump (PMCA) behaves under changing
      Ca(2+) concentrations, it is necessary to obtain information about the Ca(2+)
      dependence of the rate constants for calmodulin activation (k(act)) and for
      inactivation by calmodulin removal (k(inact)). Here we studied these constants
      for isoforms 2b and 4b. We measured the ATPase activity of these isoforms
      expressed in Sf9 cells. For both PMCA4b and 2b, k(act) increased with Ca(2+)
      along a sigmoidal curve. At all Ca(2+) concentrations, 2b showed a faster
      reaction with calmodulin than 4b but a slower off rate. On the basis of the
      measured rate constants, we simulated mathematically the behavior of these pumps
      upon repetitive changes in Ca(2+) concentration and also tested these simulations
      experimentally; PMCA was activated by 500 nm Ca(2+) and then exposed to 50 nm
      Ca(2+) for 10 to 150 s, and then Ca(2+) was increased again to 500 nm. During the
      second exposure to 500 nm Ca(2+), the activity reached steady state faster than
      during the first exposure at 500 nm Ca(2+). This memory effect is longer for
      PMCA2b than for 4b. In a separate experiment, a calmodulin-binding peptide from
      myosin light chain kinase, which has no direct interaction with the pump, was
      added during the second exposure to 500 nm Ca(2+). The peptide inhibited the
      activity of PMCA2b when the exposure to 50 nm Ca(2+) was 150 s but had little or
      no effect when this exposure was only 15 s. This suggests that the memory effect
      is due to calmodulin remaining bound to the enzyme during the period at low
      Ca(2+). The memory effect observed in PMCA2b and 4b will allow cells expressing
      either of them to remove Ca(2+) more quickly in subsequent spikes after an
      initial activating spike.

PMID- 11514556
TI  - ACTH decreases the expression and secretion of apolipoprotein B in HepG2 cell
      cultures.
AB  - Administration of adrenocorticotropic hormone (ACTH) has been shown to decrease
      plasma concentrations of apolipoprotein B (apoB) containing lipoproteins,
      including lipoprotein(a), in man. However, the mechanism behind this
      hypolipidemic effect is unknown. This study aimed at distinguishing between the
      main possibilities (increased elimination or decreased production of
      lipoproteins) using HepG2 cell cultures. Addition of ACTH to the cell culture
      medium selectively down-regulated apoB mRNA expression and apoB secretion in a
      dose-dependent manner. At 100 pmol/liter ACTH, the apoB mRNA level was about 40%
      lower than in the untreated cells, and the secretion of apoB into the medium was
      decreased to a similar extent. The expression and secretion of other
      apolipoproteins (apoA-I, apoE, and apoM), however, were not affected by ACTH.
      Under normal culture conditions the level of secretion of apoB from HepG2 cells
      is quite low. In the presence of 0.4 mmol/liter oleic acid secretion of apoB
      increased 3-fold, but this phenomenon was not seen in ACTH-treated cells. Binding
      and internalization of radiolabeled low density lipoprotein (LDL) by HepG2 cell,
      as well as LDL-receptor mRNA and scavenger receptor B-I mRNA levels, were not
      influenced by ACTH. In conclusion, ACTH directly and selectively down-regulated
      the production and secretion of apoB in HepG2 cell cultures, suggesting that a
      principal mechanism behind the cholesterol-lowering effect of ACTH in vivo may be
      a decreased production rate of apoB-containing lipoproteins from the liver.

PMID- 11514557
TI  - Regulation of heat shock transcription factor 1 by stress-induced SUMO-1
      modification.
AB  - Heat shock transcription factor 1 (HSF1) mediates the induction of heat shock
      protein gene expression in cells exposed to elevated temperature and other stress
      conditions. In response to stress HSF1 acquires DNA binding ability and localizes
      to nuclear stress granules, but the molecular mechanisms that mediate these
      events are not understood. We report that HSF1 undergoes stress-induced
      modification at lysine 298 by the small ubiquitin-related protein called SUMO-1.
      Antibodies against SUMO-1 supershift the HSF1 DNA-binding complex, and
      modification of HSF1 in a reconstituted SUMO-1 reaction system causes conversion
      of HSF1 to the DNA-binding form. HSF1 colocalizes with SUMO-1 in nuclear stress
      granules, which is prevented by mutation of lysine 298. Mutation of lysine 298
      also results in a significant decrease in stress-induced transcriptional activity
      of HSF1 in vivo. This work implicates SUMO-1 modification as an important
      modulator of HSF1 function in response to stress.

PMID- 11514558
TI  - Early postnatal cardiac changes and premature death in transgenic mice
      overexpressing a mutant form of serum response factor.
AB  - Serum response factor (SRF) is a key regulator of a number of extracellular
      signal-regulated genes important for cell growth and differentiation. A form of
      the SRF gene with a double mutation (dmSRF) was generated. This mutation reduced
      the binding activity of SRF protein to the serum response element and reduced the
      capability of SRF to activate the atrial natriuretic factor promoter that
      contains the serum response element. Cardiac-specific overexpression of dmSRF
      attenuated the total SRF binding activity and resulted in remarkable morphologic
      changes in the heart of the transgenic mice. These mice had dilated atrial and
      ventricular chambers, and their ventricular wall thicknesses were only 1/2 to 1/3
      the thickness of that of nontransgenic mice. Also these mice had smaller cardiac
      myocytes and had less myofibrils in their myocytes relative to nontransgenic
      mice. Altered gene expression and slight interstitial fibrosis were observed in
      the myocardium of the transgenic mice. All the transgenic mice died within the
      first 12 days after birth, because of the early onset of severe, dilated
      cardiomyopathy. These results indicate that dmSRF overexpression in the heart
      apparently alters cardiac gene expression and blocks normal postnatal cardiac
      growth and development.

PMID- 11514559
TI  - Antiepileptic drugs increase plasma levels of 4beta-hydroxycholesterol in humans:
      evidence for involvement of cytochrome p450 3A4.
AB  - The major cholesterol oxidation products in the human circulation are 27
      hydroxycholesterol, 24-hydroxycholesterol, and 7alpha-hydroxycholesterol. These
      oxysterols are formed from cholesterol by specific cytochrome P450 enzymes,
      CYP27, CYP46, and CYP7A, respectively. An additional oxysterol present in
      concentrations comparable with 7alpha- and 24-hydroxycholesterol is 4beta
      hydroxycholesterol. We now report that patients treated with the antiepileptic
      drugs phenobarbital, carbamazepine, or phenytoin have highly elevated levels of
      plasma 4beta-hydroxycholesterol. When patients with uncomplicated cholesterol
      gallstone disease were treated with ursodeoxycholic acid, plasma 4beta
      hydroxycholesterol increased by 45%. Ursodeoxycholic acid, as well as the
      antiepileptic drugs, are known to induce cytochrome P450 3A. Recombinant CYP3A4
      was shown to convert cholesterol to 4beta-hydroxycholesterol, whereas no
      conversion was observed with CYP1A2, CYP2C9, or CYP2B6. The concentration of
      4alpha-hydroxycholesterol in plasma was lower than the concentration of 4beta
      hydroxycholesterol and not affected by treatment with the antiepileptic drugs or
      ursodeoxycholic acid. Together, these data suggest that 4beta-hydroxycholesterol
      in human circulation is formed by a cytochrome P450 enzyme.

PMID- 11514560
TI  - Mechanism of the SDS-resistant synaptotagmin clustering mediated by the cysteine
      cluster at the interface between the transmembrane and spacer domains.
AB  - Synaptotagmin I (Syt I), a proposed major Ca(2+) sensor in the central nervous
      system, has been hypothesized as functioning in an oligomerized state during
      neurotransmitter release. We previously showed that Syts I, II, VII, and VIII
      form a stable SDS-resistant, beta-mercaptoethanol-insensitive, and Ca(2+)
      independent oligomer surrounding the transmembrane domain (Fukuda, M., and
      Mikoshiba, K. (2000) J. Biol. Chem. 275, 28180-28185), but little is known about
      the molecular mechanism of the Ca(2+)-independent oligomerization by the
      synaptotagmin family. In this study, we analyzed the Ca(2+)-independent
      oligomerization properties of Syt I and found that it shows two distinct forms of
      self-oligomerization activity: stable SDS-resistant self-oligomerization activity
      and relatively unstable SDS-sensitive self-oligomerization activity. The former
      was found to be mediated by a post-translationally modified (i.e. fatty-acylated)
      cysteine (Cys) cluster (Cys-74, Cys-75, Cys-77, Cys-79, and Cys-82) at the
      interface between the transmembrane and spacer domains of Syt I. We also show
      that the number of Cys residues at the interface between the transmembrane and
      spacer domains determines the SDS- resistant oligomerizing capacity of each
      synaptotagmin isoform: Syt II, which contains seven Cys residues, showed the
      strongest SDS-resistant oligomerizing activity in the synaptotagmin family,
      whereas Syt XII, which has no Cys residues, did not form any SDS-resistant
      oligomers. The latter SDS-sensitive self-oligomerization of Syt I is mediated by
      the spacer domain, because deletion of the whole spacer domain, including the Cys
      cluster, abolished it, whereas a Syt I(CA) mutant carrying Cys to Ala
      substitutions still exhibited self-oligomerization. Based on these results, we
      propose that the oligomerization of the synaptotagmin family is regulated by two
      distinct mechanisms: the stable SDS-resistant oligomerization is mediated by the
      modified Cys cluster, whereas the relatively unstable (SDS-sensitive)
      oligomerization is mediated by the environment of the spacer domain.

PMID- 11514561
TI  - Structure of the human 3alpha-hydroxysteroid dehydrogenase type 3 in complex with
      testosterone and NADP at 1.25-A resolution.
AB  - The first crystallographic structure of human type 3 3alpha-hydroxysteroid
      dehydrogenase (3alpha-HSD3, AKR1C2), an enzyme playing a critical role in steroid
      hormone metabolism, has been determined in complex with testosterone and NADP at
      1.25-A resolution. The enzyme's 17beta-HSD activity was studied in comparison
      with its 3alpha-HSD activity. The enzyme catalyzes the inactivation of
      dihydrotestosterone into 5alpha-androstane-3alpha,17beta-diol (3alpha-diol) as
      well as the transformation of androstenedione into testosterone. Using our
      homogeneous and highly active enzyme preparation, we have obtained 150-fold
      higher 3alpha-HSD specificity as compared with the former reports in the
      literature. Although the rat and the human 3alpha-HSDs share 81% sequence
      homology, our structure reveals significantly different geometries of the active
      sites. Substitution of the Ser(222) by a histidine in the human enzyme may compel
      the steroid to adopt a different binding to that previously described for the rat
      (Bennett, M. J., Albert, R. H., Jez, J. M., Ma, H., Penning, T. M., and Lewis, M.
      (1997) Structure 5, 799-T812). Furthermore, we showed that the affinity for the
      cofactor is higher in the human 3alpha-HSD3 than the rat enzyme due to the
      presence of additional hydrogen bonds on the adenine moiety and that the cofactor
      is present under its reduced form in the active site in our preparation.

PMID- 11514562
TI  - TIA-1 and TIAR activate splicing of alternative exons with weak 5' splice sites
      followed by a U-rich stretch on their own pre-mRNAs.
AB  - TIA-1 has recently been shown to activate splicing of specific pre-mRNAs
      transcribed from transiently transfected minigenes, and of some 5' splice sites
      in vitro, but has not been shown to activate splicing of any endogenous pre-mRNA.
      We show here that overexpression of TIA-1 or the related protein TIAR has little
      effect on splicing of several endogenous pre-mRNAs containing alternative exons,
      but markedly activates splicing of some normally rarely used alternative exons on
      the TIA-1 and TIAR pre-mRNAs. These exons have weak 5' splice sites followed by U
      rich stretches. When the U-rich stretch following the 5' splice site of a TIA-1
      alternative exon was deleted, TIAR overexpression induced use of a cryptic 5'
      splice site also followed by a U-rich stretch in place of the original splice
      site. Using in vitro splicing assays, we have shown that TIA-1 is directly
      involved in activating the 5' splice sites of the TIAR alternative exons.
      Activation requires a downstream U-rich stretch of at least 10 residues. Our
      results confirm that TIA-1 activates 5' splice sites followed by U-rich sequences
      and show that TIAR exerts a similar activity. They suggest that both proteins may
      autoregulate their expression at the level of splicing.

PMID- 11514563
TI  - Identification of a caspase-9 substrate and detection of its cleavage in
      programmed cell death during mouse development.
AB  - The caspase family of proteases represents the main machinery by which apoptosis
      occurs. In vitro studies have revealed that upstream caspases are activated in
      response to apoptotic stimuli, and the active caspases in turn process downstream
      effector caspases that are involved in the destruction of cellular structure.
      Caspase-9 is an upstream caspase that can become active in response to cellular
      damage, including deprivation of growth factors and exposure to oxidative stress
      in vitro. Little is known, however, about how activation of caspase-9 is
      temporally and spatially regulated in vivo, e.g. during development. We have
      identified vimentin as the first example of a caspase-9 substrate that is not a
      downstream procaspase. Immunohistochemical analysis, using a specific antibody
      against the vimentin fragments generated by caspase-9, showed that caspase-9
      cleaves vimentin in apoptotic cells in the embryonic nervous system and the
      interdigital regions. This result is consistent with observations that gene
      knockouts of caspase-9 and its activator, Apaf-1, result in developmental defects
      in these tissues. Our results show that the specific antibody is useful for in
      situ detection of caspase-9 activation in programmed cell death.

PMID- 11514564
TI  - A membrane-proximal basic domain and cysteine cluster in the C-terminal tail of
      CCR5 constitute a bipartite motif critical for cell surface expression.
AB  - We examined the structural requirements for cell surface expression, signaling,
      and human immunodeficiency virus co-receptor activity for the chemokine receptor,
      CCR5. Serial C-terminal truncation of CCR5 resulted in progressive loss of cell
      surface expression; mutants truncated at the 317th position and shorter were not
      detected at the cell surface. Alanine substitution of basic residues in the
      membrane-proximal domain (residues 314-322) in the context of a full-length C
      tail resulted in severe reduction in surface expression. C-terminal truncation
      that excised the three cysteines in this domain reduced surface expression, but
      further truncation of upstream basic residue(s) abolished surface expression.
      Substituting the carboxyl-terminal domain of CXCR4 for that of CCR5 failed to
      rectify the trafficking defect of the tailless CCR5. In contrast, tailless CXCR4
      or a CXCR4 chimera that exchanged the native cytoplasmic domain for that of wild
      type CCR5 was expressed at the cell surface. Deletion mutants that expressed at
      the cell surface responded to chemokine stimulation and mediated human
      immunodeficiency virus entry. Substitution of all serine and threonine residues
      in the C-terminal tail of CCR5 abolished chemokine-mediated receptor
      phosphorylation but preserved downstream signaling (Ca(2+) flux), while
      substitutions of tyrosine residues in the C-tail affected neither phenotype. CCR5
      mutants that failed to traffic to the plasma membrane did not exhibit obvious
      changes in metabolic turnover and were retained in the Golgi or pre-Golgi
      compartments(s). Thus, the basic domain (-KHIAKRF-) and the cysteine cluster (
      CKCC-) in the C-terminal tail of CCR5 function cooperatively for optimal surface
      expression.

PMID- 11514565
TI  - Differential utilization of enzyme-substrate interactions for acylation but not
      deacylation during the catalytic cycle of Kex2 protease.
AB  - Kex2 protease from Saccharomyces cerevisiae is the prototype for a family of
      eukaryotic proprotein processing proteases belonging to the subtilase superfamily
      of serine proteases. Kex2 can be distinguished from degradative subtilisins on
      the basis of stringent substrate specificity and distinct pre-steady-state
      behavior. To better understand these mechanistic differences, we have examined
      the effects of substrate residues at P(1) and P(4) on individual steps in the
      Kex2 catalytic cycle with a systematic series of isosteric peptidyl amide and
      ester substrates. The results demonstrate that substrates based on known,
      physiological cleavage sites exhibit high acylation rates (> or =550 s(-1)) with
      Kex2. Substitution of Lys for the physiologically correct Arg at P(1) resulted in
      a > or =200-fold drop in acylation rate with almost no apparent effect on binding
      or deacylation. In contrast, substitution of the physiologically incorrect Ala
      for Nle at P(4) resulted in a much smaller defect in acylation and a modest but
      significant effect on binding with Lys at P(1). This substitution also had no
      effect on deacylation. These results demonstrate that Kex2 utilizes enzyme
      substrate interactions in different ways at different steps in the catalytic
      cycle, with the S(1)-P(1) contact providing a key specificity determinant at the
      acylation step.

PMID- 11514566
TI  - A Fas-associated death domain protein-dependent mechanism mediates the apoptotic
      action of non-steroidal anti-inflammatory drugs in the human leukemic Jurkat cell
      line.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) are inhibitors of cyclooxygenase-1
      and -2 and are useful for prevention and cure of cancers, especially colon and
      rectal cancers. The NSAIDs indomethacin and sulindac sulfide have been shown to
      induce apoptosis of colon epithelial cancer cells by a Bax-dependent mechanism
      that involves mitochondria-mediated activation of a caspase-9-dependent pathway.
      In this report, we demonstrate that indomethacin and sulindac sulfide induce
      apoptosis of human leukemic Jurkat cells by a mechanism that requires the Fas
      associated Death Domain Protein-mediated activation of a caspase-8-dependent
      pathway. Therefore, NSAIDs induce apoptosis by different mechanisms depending on
      the cell type.

PMID- 11514568
TI  - Kinetics of nonproteolytic incorporation of a protein ligand into thermally
      activated alpha 2-macroglobulin: evidence for a novel nascent state.
AB  - We have previously shown that antigens complexed to the receptor-recognized form
      of alpha(2)-macroglobulin (alpha(2)M*) demonstrate enhanced immune responsiveness
      mediated by the low density lipoprotein receptor-related protein LRP/CD91.
      Recently, we developed a proteinase-independent method to covalently bind
      antigens to alpha(2)M*. Given the potential applications of this chemistry, we
      analyzed the kinetics, thermodynamics, and pH dependence of this reaction. The
      incorporation of lysozyme into alpha(2)M* was a mixed bimolecular second-order
      reaction with a specific rate constant of 91.0 +/- 6.9 m(-1) s(-1), 50.0 degrees
      C, pH 7.4. The activation energy, activation entropy, and Gibbs' free energy at
      50.0 degrees C were 156 kJ mol(-1), 266 J mol(-1) K(-1), and 70 kJ mol(-1),
      respectively. The rate of incorporation increased as a function of pH from pH 5.0
      to 7.0 and was unchanged thereafter. Furthermore, the reaction between alpha(2)M*
      and lysozyme was irreversible. The data are consistent with a two-step mechanism.
      In the first step, alpha(2)M* reforms its thiol ester bond, entering a reactive
      state that mimics the proteolytically induced "nascent state." In the rate
      limiting second step, the reformed bond quickly undergoes nucleophilic attack by
      lysozyme. The kinetic equations derived in this study are the basis for
      optimizing the formation of stable alpha(2)M*.antigen complexes.

PMID- 11514567
TI  - Ternary complexes and cooperative interplay between NCoA-62/Ski-interacting
      protein and steroid receptor coactivators in vitamin D receptor-mediated
      transcription.
AB  - The vitamin D receptor (VDR) is a ligand-dependent transcriptional factor that
      binds to vitamin D-responsive elements as a heterodimer with retinoid X receptor
      (RXR) to regulate target gene transcription. The steroid receptor coactivator
      (SRC) proteins are coactivators that interact with the AF-2 domain of VDR to
      augment 1,25-dihydroxyvitamin D3-dependent transcription. In contrast, NCoA
      62/Ski-interacting protein (SKIP) is a distinct, activation function-2
      independent coactivator for VDR. The current study examined whether these two
      distinct classes of coactivators impact functionally on VDR-mediated
      transcription. Using a ternary complex binding assay, we observed a marked
      preference for the direct interaction of NCoA-62/SKIP with the VDR-RXR
      heterodimer as compared with the VDR-VDR homodimer or VDR monomer. The liganded
      VDR also formed a ternary complex with NCoA-62/SKIP and SRC proteins in vitro.
      Competition experiments using LXXLL peptides showed that NCoA-62/SKIP and SRC
      coactivators contact different domains of the VDR-RXR heterodimer. Synergistic
      interplays were observed between NCoA-62/SKIP and SRC coactivators in VDR
      mediated transcriptional assays, and protein interference assays indicated a
      requirement for both NCoA-62/SKIP and SRCs in VDR- mediated transcription. These
      studies suggest that the ligand-dependent and simultaneous interaction of NCoA
      62/SKIP and SRC coactivators with distinct interaction domains within the VDR-RXR
      heterodimer results in cooperative interplays between coactivators in VDR
      mediated transcription.

PMID- 11514569
TI  - Effects of spectator ligands on the specific recognition of intrastrand platinum
      DNA cross-links by high mobility group box and TATA-binding proteins.
AB  - The results presented describe the effects of various spectator ligands, attached
      to a platinum 1,2-intrastand d(GpG) cross-link in duplex DNA, on the binding of
      high mobility group box (HMGB) domains and the TATA-binding protein (TBP). In
      addition to cisplatin-modified DNA, 15-base pair DNA probes modified by [Pt(1R,2R
      diaminocyclohexane)](2+), cis-[Pt(NH(3))(cyclohexylamine)](2+),
      [Pt(ethylenediamine)](2+), cis-[Pt(NH(3))(cyclobutylamine)](2+), and cis
      [Pt(NH(3))(2-picoline)](2+) were examined. Electrophoretic mobility shift assays
      show that both the A and B domains of HMGB1 as well as TBP discriminate between
      different platinum-DNA adducts. HMGB1 domain A is the most sensitive to the
      nature of the spectator ligands on platinum. The effect of the spectator ligands
      on protein binding also depends highly on the base pairs flanking the platinated
      d(GpG) site. Double-stranded oligonucleotides containing the AG*G*C sequence,
      where the asterisks denote the sites of platination, with different spectator
      ligands are only moderately discriminated by the HMGB proteins and TBP, but the
      recognition of dsTG*G*A is highly dependent on the ligands. The effects of HMGB1
      overexpression in a BG-1 ovarian cancer cell line, induced by steroid hormones,
      on the sensitivity of cells treated with [Pt(1R,2R-diaminocyclohexane)Cl(2)] and
      cis-[Pt(NH(3))(cyclohexylamine)Cl(2)] were also examined. The results suggest
      that HMGB1 protein levels influence the cellular processing of cis-[Pt(NH(3))-
      (cyclohexylamine)](2+), but not [Pt((1R,2R)-diaminocyclohexane)](2+), DNA
      lesions. This result is consistent with the observed binding of HMGB1a to
      platinum-modified dsTG*G*A probes but not with the binding affinity of HMGB1a and
      HMGB1 to platinum-damaged dsAG*G*C oligonucleotides. These experiments reinforce
      the importance of sequence context in platinum-DNA lesion recognition by cellular
      proteins.

PMID- 11514570
TI  - Structural remodeling of an A + U-rich RNA element by cation or AUF1 binding.
AB  - Association of AUF1 with A + U-rich elements (AREs) induces rapid cytoplasmic
      degradation of mRNAs containing these sequences, involving the recruitment or
      assembly of multisubunit trans-acting complexes on the mRNA. Recently, we
      reported that Mg(2+)-induced conformational changes in the ARE from tumor
      necrosis factor alpha mRNA inhibited AUF1 binding and oligomerization activities
      on this substrate (Wilson, G. M., Sutphen, K., Chuang, K., and Brewer, G. (2001)
      J. Biol. Chem. 276, 8695-8704). In this study, resonance energy transfer was
      employed to characterize structural changes in RNA substrates in response to
      cation- and AUF1-binding events. An RNA substrate containing the tumor necrosis
      factor alpha ARE displayed a weak conformational transition in the absence of
      added cations but was cooperatively stabilized by Mg(2+). Additional assays
      demonstrated a strong preference for small, multivalent cations, suggesting that
      the folded RNA structure was stabilized by counterion neutralization at discrete
      regions of high negative charge density. Association of AUF1 with cognate RNA
      substrates also induced formation of condensed RNA structures, although distinct
      from the folded structure stabilized by multivalent cations. Taken together,
      these experiments indicate that association of AUF1 with an ARE may function to
      remodel local RNA structures, which may be a prerequisite for subsequent
      recruitment of additional trans-acting factors.

PMID- 11514571
TI  - Protein kinase D potentiates DNA synthesis and cell proliferation induced by
      bombesin, vasopressin, or phorbol esters in Swiss 3T3 cells.
AB  - We examined whether protein kinase D (PKD) overexpression in Swiss 3T3 cells
      potentiates the proliferative response to either the G protein-coupled receptor
      agonists bombesin and vasopressin or the biologically active phorbol ester
      phorbol 12,13-dibutyrate (PDBu). In order to generate Swiss 3T3 cells stably
      overexpressing PKD, cultures of these cells were infected with retrovirus
      encoding murine PKD and green fluorescent protein (GFP) expressed as two separate
      proteins translated from the same mRNA. GFP was used as a marker for selection of
      PKD-positive cells. PKD overexpressed in Swiss 3T3 cells was dramatically
      activated by cell treatment with bombesin or PDBu as judged by in vitro kinase
      autophosphorylation assays and exogenous substrate phosphorylation.
      Concomitantly, these stimuli induced PKD phosphorylation at Ser(744), Ser(748),
      and Ser(916). PKD activation and phosphorylation were prevented by exposure of
      the cells to protein kinase C-specific inhibitors. Addition of bombesin,
      vasopressin, or PDBu to cultures of Swiss 3T3 cells overexpressing PKD induced a
      striking increase in DNA synthesis and cell number compared with cultures of
      Swiss 3T3-GFP cells. In contrast, stimulation of DNA synthesis in response to
      epidermal growth factor, which acts via protein kinase C/PKD-independent
      pathways, was not enhanced. Our results demonstrate that overexpression of PKD
      selectively potentiates mitogenesis induced by bombesin, vasopressin, or PDBu in
      Swiss 3T3 cells.

PMID- 11514572
TI  - The protein tyrosine phosphatase TCPTP suppresses the tumorigenicity of
      glioblastoma cells expressing a mutant epidermal growth factor receptor.
AB  - Glioblastoma multiforme (GBM) is the most aggressive type of glioma and GBMs
      frequently contain amplifications or mutations of the EGFR gene. The most common
      mutation results in a truncated receptor tyrosine kinase known as Delta EGFR that
      signals constitutively and promotes GBM growth. Here, we report that the 45-kDa
      variant of the protein tyrosine phosphatase TCPTP (TC45) can recognize Delta EGFR
      as a cellular substrate. TC45 dephosphorylated Delta EGFR in U87MG glioblastoma
      cells and inhibited mitogen-activated protein kinase ERK2 and
      phosphatidylinositol 3-kinase signaling. In contrast, the substrate-trapping TC45
      D182A mutant, which is capable of forming stable complexes with TC45 substrates,
      suppressed the activation of ERK2 but not phosphatidylinositol 3-kinase. TC45
      inhibited the proliferation and anchorage-independent growth of Delta EGFR cells
      but TC45-D182A only inhibited cellular proliferation. Notably, neither TC45 nor
      TC45-D182A inhibited the proliferation of U87MG cells that did not express Delta
      EGFR. Delta EGFR activity was necessary for the activation of ERK2, and
      pharmacological inhibition of ERK2 inhibited the proliferation of Delta EGFR
      expressing U87MG cells. Expression of either TC45 or TC45-D182A also suppressed
      the growth of Delta EGFR-expressing U87MG cells in vivo and prolonged the
      survival of mice implanted intracerebrally with these tumor cells. These results
      indicate that TC45 can inhibit the Delta EGFR-mediated activation of ERK2 and
      suppress the tumorigenicity of Delta EGFR-expressing glioblastoma cells in vivo.

PMID- 11514573
TI  - Distinct histidine residues control the acid-induced activation and inhibition of
      the cloned K(ATP) channel.
AB  - The modulation of K(ATP) channels during acidosis has an impact on vascular tone,
      myocardial rhythmicity, insulin secretion, and neuronal excitability. Our
      previous studies have shown that the cloned Kir6.2 is activated with mild
      acidification but inhibited with high acidity. The activation relies on His-175,
      whereas the molecular basis for the inhibition remains unclear. To elucidate
      whether the His-175 is indeed the protonation site and what other structures are
      responsible for the pH-induced inhibition, we performed these studies. Our data
      showed that the His-175 is the only proton sensor whose protonation is required
      for the channel activation by acidic pH. In contrast, the channel inhibition at
      extremely low pH depended on several other histidine residues including His-186,
      His-193, and His-216. Thus, proton has both stimulatory and inhibitory effects on
      the Kir6.2 channels, which attribute to two sets of histidine residues in the C
      terminus.

PMID- 11514574
TI  - The histone acetyltransferase domains of CREB-binding protein (CBP) and p300/CBP
      associated factor are not necessary for cooperativity with the class II
      transactivator.
AB  - The class II transactivator (CIITA) is a transcriptional co-activator regulating
      the constitutive and interferon-gamma-inducible expression of class II major
      histocompatibility complex (MHC) and related genes. Promoter remodeling occurs
      following CIITA induction, suggesting the involvement of chromatin remodeling
      factors. Transcription of numerous genes requires the histone acetyltransferase
      (HAT) activities of CREB-binding protein (CBP), p300, and/or p300/CBP-associated
      factor (pCAF). These co-activators cooperate with CIITA and are hypothesized to
      promote class II major histocompatibility complex transcription through their HAT
      activity. To directly test this, we used HAT-defective CBP and pCAF. We
      demonstrate that cooperation between CIITA and CBP is independent of CBP HAT
      activity. Further, although pCAF enhances CIITA-mediated transcription, pCAF HAT
      domain dependence appears contingent upon the concentration of available CIITA.
      When HAT-defective CBP and pCAF are both present, cooperativity with CIITA is
      maintained. Consistent with a recent report, we show that nuclear localization of
      CIITA is enhanced by lysine 144, an in vitro target of pCAF-mediated HAT. Yet we
      find that neither mutation of lysine 144 nor deletion of residues 132-209 affects
      transcriptional cooperation with CBP or pCAF. Thus, acetylation of this residue
      may not be the primary mechanism for pCAF/CBP cooperation with CIITA. In
      conclusion, the HAT activities of the co-activators are not necessary for
      cooperation with CIITA.

PMID- 11514575
TI  - Molecular cloning and expression of a human chondroitin synthase.
AB  - We have identified a human chondroitin synthase from the HUGE (human unidentified
      gene-encoded large proteins) protein data base by screening with two keywords:
      "one transmembrane domain" and "galactosyltransferase family." The identified
      protein consists of 802 amino acids with a type II transmembrane protein
      topology. The protein showed weak homology to the beta1,3-galactosyltransferase
      family on the amino-terminal side and to the beta1,4-galactosyltransferase family
      on the carboxyl-terminal side. The expression of a soluble recombinant form of
      the protein in COS-1 cells produced an active enzyme, which transferred not only
      the glucuronic acid (GlcUA) from UDP-[(14)C]GlcUA but also N-acetylgalactosamine
      (GalNAc) from UDP-[(3)H]GalNAc to the polymer chondroitin. Identification of the
      reaction products demonstrated that the enzyme was chondroitin synthase, with
      both beta1,3-GlcUA transferase and beta1,4-GalNAc transferase activities. The
      coding region of the chondroitin synthase was divided into three discrete exons
      and localized to chromosome 15. Northern blot analysis revealed that the
      chondroitin synthase gene exhibited ubiquitous but markedly differential
      expression in the human tissues examined. Thus, we demonstrated that analogous to
      human heparan sulfate polymerases, the single polypeptide chondroitin synthase
      possesses two glycosyltransferase activities required for chain polymerization.

PMID- 11514576
TI  - CBF/NF-Y functions both in nucleosomal disruption and transcription activation of
      the chromatin-assembled topoisomerase IIalpha promoter. Transcription activation
      by CBF/NF-Y in chromatin is dependent on the promoter structure.
AB  - To understand the role of CCAAT-binding factor (CBF) in transcription in the
      context of chromatin-assembled DNA, we used regularly spaced nucleosomal DNA
      using topoisomerase IIalpha (topo IIalpha) and alpha2(1) collagen promoter
      templates, which were subsequently reconstituted in an in vitro transcription
      reaction. Binding of CBF to the nucleosomal wild-type topo IIalpha promoter
      containing four CBF-binding sites disrupted the regular nucleosomal structure not
      only in the promoter region containing the CBF-binding sites but also in the
      downstream region over the transcription start site. In contrast, no nucleosome
      disruption was observed in a mutant topo IIalpha promoter containing mutations in
      all CBF-binding sites. Interestingly, CBF also activated transcription from
      nucleosomal wild-type topo IIalpha promoter. In this experiment, a promoter
      containing one wild-type CBF-binding site was activated very weakly, whereas the
      promoter containing mutations in all sites was not activated by CBF. A truncated
      CBF that lacked the glutamine-rich domains did not activate transcription from
      nucleosomal wild-type topo IIalpha promoter but disrupted the nucleosomal
      structure about as much as did the binding of full-length CBF. Two nucleosomal
      mouse alpha2(1) collagen promoter DNAs, one containing a single and the other
      containing four CBF- binding sites, were also reconstituted in an in vitro
      transcription reaction. None of the nucleosomal collagen promoters was activated
      by CBF. However, both of these collagen promoters were activated by CBF when the
      transcription reaction was performed using naked DNA templates. Binding of CBF to
      the nucleosomal collagen promoter containing four binding sites disrupted the
      nucleosomal structure, similarly as observed in the topo IIalpha promoter.
      Altogether this study indicates that CBF-mediated nucleosomal disruption occurred
      independently of transcription activation. It also suggests that specific
      promoter structure may play a role in the CBF-mediated transcription activation
      of nucleosomal topo IIalpha promoter template.

PMID- 11514578
TI  - Grb4/Nckbeta acts as a nuclear repressor of v-Abl-induced transcription from c
      jun/c-fos promoter elements.
AB  - Grb4 is an adaptor protein consisting of three src homology (SH) 3 domains and a
      single SH2 domain. We previously cloned Grb4 as a direct interacting partner of
      Bcr-Abl and v-Abl via the Grb4 SH2 domain. We now show that overexpression of
      Grb4 results in significant inhibition of v-Abl-induced transcriptional
      activation from promitogenic enhancer elements such as activator protein 1 (AP-1)
      and serum-responsive element (SRE). We demonstrate that the inhibitory activity
      of Grb4 is independent of the direct interaction of v-Abl and Grb4: a Grb4 mutant
      that lacks a functional SH2 domain shows an even more pronounced inhibition of AP
      1/SRE. Further mutational analysis revealed that the first two SH3 domains
      primarily mediate the inhibitory function. The inhibitory activity of Grb4 is
      specific for c-jun/c-fos-regulated promoter elements and is located downstream of
      MEKK1 and JNK because co-expression of Grb4 resulted in down-regulation of MEKK1
      induced AP-1 activity without affecting JNK activity. Thus, the nuclear pool of
      Grb4 is likely to mediate this inhibition. Indeed, cell fractionation and
      fluorescence microscopy studies revealed that the stronger inhibitory potential
      of the Grb4 SH2 mutant occurred in conjunction with increased nuclear
      localization of this mutant. Our results suggest a novel role for Grb4 in the
      inhibition of promitogenic enhancer elements such as 12-O-tetradecanoylphorbol-13
      acetate-responsive element and SRE.

PMID- 11514577
TI  - Human phosphatidylethanolamine-binding protein facilitates heterotrimeric G
      protein-dependent signaling.
AB  - In this study we report that human phosphatidylethanolamine-binding protein
      (hPBP) facilitates heterotrimeric G protein-coupled signaling. In Xenopus laevis
      oocytes, coexpression of hPBP with human mu opioid receptor, human delta opioid
      receptor, or human somatostatin receptor 2 evoked an agonist-induced increase in
      potassium conductance of G protein-activated inwardly rectifying potassium
      channels. This activation of heterotrimeric G protein signaling in oocytes could
      also be elicited by injection of bacterially overexpressed and purified hPBP.
      Stimulatory effect was pertussis toxin-sensitive and present even in the absence
      of coexpressed receptors. Additionally, an increase in G protein-mediated
      inhibition of adenylate cyclase activity, measured by the inhibition of forskolin
      mediated cAMP accumulation, could be detected in HEK293 and NIH3T3 cells after
      expression of hPBP and in Xenopus oocytes after injection of hPBP. As
      [(35)S]guanosine 5'-3-O-(thio)triphosphate (GTPgammaS) binding to membranes
      prepared from hPBP-expressing cells was significantly elevated and recombinant
      hPBP dose-dependently stimulated [(35)S]GTPgammaS binding to native membranes,
      the results presented provide strong evidence that hPBP-induced effects are G
      protein-dependent. These data suggest a novel function of hPBP in regulating G
      protein and G protein-coupled receptor signaling in vivo.

PMID- 11514579
TI  - Relationship between calnexin and BiP in suppressing aggregation and promoting
      refolding of protein and glycoprotein substrates.
AB  - Calnexin (CNX) is a membrane protein of the endoplasmic reticulum that has been
      defined primarily as a lectin, yet is capable of functioning as a molecular
      chaperone with non-glycosylated proteins in vitro. Here, we assess the relative
      contributions of the oligosaccharide- and polypeptide-binding sites of CNX to its
      in vitro chaperone functions by comparing it with the Hsp70 chaperone of the
      endoplasmic reticulum, BiP. Both proteins were equally effective in preventing
      the aggregation of non-glycosylated citrate synthase, indicating that the
      polypeptide-binding site of CNX is capable of functioning at a level similar to
      that of Hsp70. However, when confronted with glycoprotein substrates, the lectin
      site of CNX provided a significant advantage over BiP in suppressing aggregation.
      CNX also cooperated with BiP and the J domain of Sec63p in the ATP-dependent
      refolding of glycoprotein and non-glycosylated substrates. The lectin site of CNX
      was essential for refolding of the glycoprotein. These findings reinforce the
      function of CNX as a bona fide chaperone and illustrate how its lectin site
      confers advantages relative to other chaperones when confronted with glycoprotein
      substrates.

PMID- 11514580
TI  - Expression, purification, and characterization of recombinant HIV gp140. The gp41
      ectodomain of HIV or simian immunodeficiency virus is sufficient to maintain the
      retroviral envelope glycoprotein as a trimer.
AB  - Efforts to understand the molecular basis of human immunodeficiency virus (HIV)
      envelope glycoprotein function have been hampered by the inability to generate
      sufficient quantities of homogeneous material. We now report on the high level
      expression, purification, and characterization of soluble HIV gp140 ectodomain
      proteins in Chinese hamster ovary-Lec3.2.8.1 cells. Gel filtration and analytical
      ultracentrifugation show that the uncleaved ADA strain-derived gp140 proteins are
      trimeric without further modification required to maintain oligomers. These spike
      proteins are native as judged by soluble CD4 (sCD4) (K(D) = 1-2 nm) and
      monoclonal antibody binding studies using surface plasmon resonance. CD4 ligation
      induces conformational change in the trimer, exposing the chemokine receptor
      binding site as assessed by 17b monoclonal antibody reactivity. Lack of anti
      cooperativity in sCD4-ADA trimer interaction distinct from that observed with
      sCD4-SIV mac32H implies quaternary structural differences in ground states of
      their respective spike proteins.

PMID- 11514581
TI  - Aquaporin-5 dependent fluid secretion in airway submucosal glands.
AB  - Fluid and macromolecule secretion by submucosal glands in mammalian airways is
      believed to play an important role in airway defense and surface liquid
      homeostasis and in the pathogenesis of cystic fibrosis. Immunocytochemistry
      revealed strong expression of aquaporin water channel AQP5 at the luminal
      membrane of serous epithelial cells in submucosal glands throughout the mouse
      nasopharynx and upper airways and AQP4 at the contralateral basolateral membrane
      in some glands. Novel methods were applied to measure secretion rates and
      composition of gland fluid in wild type mice and knockout mice lacking AQP4 or
      AQP5. In mice breathing through a tracheotomy, total gland fluid output was
      measured from the dilution of a volume marker present in the fluid-filled
      nasopharynx and upper trachea. Pilocarpine-stimulated fluid secretion was 4.3 +/-
      0.4 microl/min in wild type mice, 4.9 +/- 0.9 microl/min in AQP4 null mice, and
      1.9 +/- 0.3 microl/min in AQP5 null mice (p < 0.001). Similar results were
      obtained when secreted fluid was collected in the oil-filled nasopharyngeal
      cavity. Real-time video imaging of fluid droplets secreted from individual
      submucosal glands near the larynx in living mice showed a 57 +/- 4% reduced fluid
      secretion rate in AQP5 null mice. Analysis of secreted fluid showed a 2.3 +/- 0.2
      fold increase in total protein in AQP5 null mice and a smaller increase in [Cl(
      )], suggesting intact protein and salt secretion across a relatively water
      impermeable epithelial barrier. Submucosal gland morphology and density did not
      differ significantly in wild type versus AQP5 null mice. These results indicate
      that AQP5 facilitates fluid secretion in submucosal glands and that the luminal
      membrane of gland epithelial cells is the rate-limiting barrier to water
      movement. Modulation of gland AQP5 expression or function might provide a novel
      approach to treat hyperviscous gland secretions in cystic fibrosis and excessive
      fluid secretions in infectious or allergic bronchitis/rhinitis.

PMID- 11514582
TI  - pH alterations "reset" Ca2+ sensitivity of brain Na+ channel 2, a
      degenerin/epithelial Na+ ion channel, in planar lipid bilayers.
AB  - Members of the degenerin/epithelial Na(+) channel superfamily of ion channels
      subserve many functions, ranging from whole body sodium handling to
      mechanoelectrical transduction. We studied brain Na(+) channel 2 (BNaC-2) in
      planar lipid bilayers to examine its single channel properties and regulation by
      Ca(2+). Upon incorporation of vesicles made from membranes of oocytes expressing
      either wild-type (WT) BNaC-2 or BNaC-2 with a gain-of-function (GF) point
      mutation (G433F), functional channels with different properties were obtained. WT
      BNaC-2 resided in a closed state with short openings, whereas GF BNaC-2 was
      constitutively activated; a decrease in the pH in the trans compartment of the
      bilayer activated WT BNaC-2 and decreased its permeability for Na(+) over K(+).
      Moreover, these maneuvers made the WT channel more resistant to amiloride. In
      contrast, GF BNaC-2 did not respond to a decrease in pH, and its amiloride
      sensitivity and selectivity for Na(+) over K(+) were unaffected by this pH
      change. Buffering the bathing solutions with EGTA to reduce the free [Ca(2+)] to
      <10 nm increased WT single channel open probability 10-fold, but not that of GF
      BNaC-2. Ca(2+) blocked both WT and GF BNaC-2 in a dose- and voltage-dependent
      fashion; single channel conductances were unchanged. A drop in pH reduced the
      ability of Ca(2+) to inhibit these channels. These results show that BNaC-2 is an
      amiloride-sensitive sodium channel and suggest that pH activation of these
      channels could be, in part, a consequence of H(+) "interference" with channel
      regulation by Ca(2+).

PMID- 11514583
TI  - Regulation of the hypoxia-inducible factor 1alpha by the inflammatory mediators
      nitric oxide and tumor necrosis factor-alpha in contrast to desferroxamine and
      phenylarsine oxide.
AB  - Hypoxic/ischemic conditions provoke activation of the hypoxia-inducible factor-1
      (HIF-1), which functions as a transcription factor. HIF-1 is composed of the HIF
      1alpha and -beta subunits, and stability regulation occurs via
      accumulation/degradation of HIF-1alpha with the notion that a prolyl hydroxylase
      accounts for changes in protein level. In addition, there is evidence that HIF-1
      is up-regulated by diverse agonists during normoxia. We investigated the impact
      of inflammatory mediators nitric oxide (NO) and tumor necrosis factor-alpha (TNF
      alpha) on HIF-1alpha regulation. For comparison, LLC-PK(1) cells were exposed to
      hypoxia, stimulated with desferroxamine (DFX, known to mimic hypoxia), and the
      thiol-cross-linking agent phenylarsine oxide (PAO). Although all stimuli elicited
      HIF-1alpha stabilization with differences in the time-dependent accumulation
      pattern, significant variations appeared with regard to signaling. With the use
      of a superoxide anion (O(2-)) generator, we established an O(2-)-sensitive
      pathway that blocked HIF-1alpha stabilization in response to NO and TNF-alpha
      while DFX- and PAO-evoked HIF-1alpha stabilization appeared O(2-)-insensitive. NO
      and TNF-alpha signaling required phosphorylation events, especially activation of
      the phosphatidylinositol 3-kinase/Akt, which is in contrast to DFX and PAO. Based
      on HIF-1-dependent luciferase reporter gene analysis, it was found that, in
      contrast to NO and TNF-alpha, PAO resembled a stimulus that induced a
      dysfunctional HIF-1 complex. These data indicate that diverse agonists activate
      HIF-1alpha under normoxic conditions by employing different signaling pathways.

PMID- 11514584
TI  - Abp1p and cortactin, new "hand-holds" for actin.
AB  - Recently, two new ligands of the Arp2/3 complex have been described that may shed
      light on the way cells organize complex networks of actin in response to signals.
      Abp1p, a yeast protein involved in endocytosis, and cortactin, a mammalian src
      substrate, both enhance the ability of the Arp2/3 complex to assemble branched
      actin filament networks.

PMID- 11514585
TI  - Centromere identity in Drosophila is not determined in vivo by replication
      timing.
AB  - Centromeric chromatin is uniquely marked by the centromere-specific histone CENP
      A. For assembly of CENP-A into nucleosomes to occur without competition from H3
      deposition, it was proposed that centromeres are among the first or last
      sequences to be replicated. In this study, centromere replication in Drosophila
      was studied in cell lines and in larval tissues that contain minichromosomes that
      have structurally defined centromeres. Two different nucleotide incorporation
      methods were used to evaluate replication timing of chromatin containing CID, a
      Drosophila homologue of CENP-A. Centromeres in Drosophila cell lines were
      replicated throughout S phase but primarily in mid S phase. However, endogenous
      centromeres and X-derived minichromosome centromeres in vivo were replicated
      asynchronously in mid to late S phase. Minichromosomes with structurally intact
      centromeres were replicated in late S phase, and those in which centric and
      surrounding heterochromatin were partially or fully deleted were replicated
      earlier in mid S phase. We provide the first in vivo evidence that centromeric
      chromatin is replicated at different times in S phase. These studies indicate
      that incorporation of CID/CENP-A into newly duplicated centromeres is independent
      of replication timing and argue against determination of centromere identity by
      temporal sequestration of centromeric chromatin replication relative to bulk
      genomic chromatin.

PMID- 11514586
TI  - The BPAG1 locus: Alternative splicing produces multiple isoforms with distinct
      cytoskeletal linker domains, including predominant isoforms in neurons and
      muscles.
AB  - Bullous pemphigoid antigen 1 (BPAG1) is a member of the plakin family with
      cytoskeletal linker properties. Mutations in BPAG1 cause sensory neuron
      degeneration and skin fragility in mice. We have analyzed the BPAG1 locus in
      detail and found that it encodes different interaction domains that are combined
      in tissue-specific manners. These domains include an actin-binding domain (ABD),
      a plakin domain, a coiled coil (CC) rod domain, two different potential
      intermediate filament-binding domains (IFBDs), a spectrin repeat (SR)-containing
      rod domain, and a microtubule-binding domain (MTBD). There are at least three
      major forms of BPAG1: BPAG1-e (302 kD), BPAG1-a (615 kD), and BPAG1-b (834 kD).
      BPAG1-e has been described previously and consists of the plakin domain, the CC
      rod domain, and the first IFBD. It is the primary epidermal BPAG1 isoform, and
      its absence that is the likely cause of skin fragility in mutant mice. BPAG1-a is
      the major isoform in the nervous system and a homologue of the microtubule actin
      cross-linking factor, MACF. BPAG1-a is composed of the ABD, the plakin domain,
      the SR-containing rod domain, and the MTBD. The absence of BPAG1-a is the likely
      cause of sensory neurodegeneration in mutant mice. BPAG1-b is highly expressed in
      muscles, and has extra exons encoding a second IFBD between the plakin and SR
      containing rod domains of BPAG1-a.

PMID- 11514587
TI  - Regulation of cytokine-independent survival kinase (CISK) by the Phox homology
      domain and phosphoinositides.
AB  - PKB/Akt and serum and glucocorticoid-regulated kinase (SGK) family kinases are
      important downstream targets of phosphatidylinositol 3 (PI-3) kinase and have
      been shown to mediate a variety of cellular processes, including cell growth and
      survival. Although regulation of Akt can be achieved through several mechanisms,
      including its phosphoinositide-binding Pleckstrin homology (PH) domain, how SGK
      kinases are targeted and regulated remains to be elucidated. Unlike Akt, cytokine
      independent survival kinase (CISK)/SGK3 contains a Phox homology (PX) domain. PX
      domains have been implicated in several cellular events involving membrane
      trafficking. However, their precise function remains unknown. We demonstrate here
      that the PX domain of CISK interacts with phosphatidylinositol (PtdIns)(3,5)P2,
      PtdIns(3,4,5)P3, and to a lesser extent PtdIns(4,5)P2. The CISK PX domain is
      required for targeting CISK to the endosomal compartment. Mutation in the PX
      domain that abolished its phospholipid binding ability not only disrupted CISK
      localization, but also resulted in a decrease in CISK activity in vivo. These
      results suggest that the PX domain regulates CISK localization and function
      through its direct interaction with phosphoinositides. Therefore, CISK and Akt
      have evolved to utilize different lipid binding domains to accomplish a similar
      mechanism of activation in response to PI-3 kinase signaling.

PMID- 11514588
TI  - Elevating the level of Cdc34/Ubc3 ubiquitin-conjugating enzyme in mitosis
      inhibits association of CENP-E with kinetochores and blocks the metaphase
      alignment of chromosomes.
AB  - Cdc34/Ubc3 is a ubiquitin-conjugating enzyme that functions in targeting proteins
      for proteasome-mediated degradation at the G1 to S cell cycle transition.
      Elevation of Cdc34 protein levels by microinjection of bacterially expressed
      Cdc34 into mammalian cells at prophase inhibited chromosome congression to the
      metaphase plate with many chromosomes remaining near the spindle poles.
      Chromosome condensation and nuclear envelope breakdown occurred normally, and
      chromosomes showed oscillatory movements along mitotic spindle microtubules. Most
      injected cells arrested in a prometaphase-like state. Kinetochores, even those of
      chromosomes that failed to congress, possessed the normal trilaminar plate
      ultrastructure. The elevation of Cdc34 protein levels in early mitosis
      selectively blocked centromere protein E (CENP-E), a mitotic kinesin, from
      associating with kinetochores. Other proteins, including two CENP-E-associated
      proteins, BubR1 and phospho-p42/p44 mitogen-activated protein kinase, and mitotic
      centromere-associated kinesin, cytoplasmic dynein, Cdc20, and Mad2, all exhibited
      normal localization to kinetochores. Proteasome inhibitors did not affect the
      prometaphase arrest induced by Cdc34 injection. These studies suggest that CENP-E
      targeting to kinetochores is regulated by ubiquitylation not involving proteasome
      mediated degradation.

PMID- 11514589
TI  - Disruption of cytoskeletal integrity impairs Gi-mediated signaling due to
      displacement of Gi proteins.
AB  - beta1 integrins play a crucial role as cytoskeletal anchorage proteins. In this
      study, the coupling of the cytoskeleton and intracellular signaling pathways was
      investigated in beta1 integrin deficient (-/-) embryonic stem cells. Muscarinic
      inhibition of the L-type Ca2+ current (ICa) and activation of the acetylcholine
      activated K+ current (IK,ACh) was found to be absent in beta1 integrin-/-
      cardiomyocytes. Conversely, beta adrenoceptor-mediated modulation of ICa was
      unaffected by the absence of beta1 integrins. This defect in muscarinic signaling
      was due to defective G protein coupling. This was supported by deconvolution
      microscopy, which demonstrated that Gi exhibited an atypical subcellular
      distribution in the beta1 integrin-/- cardiomyocytes. A critical role of the
      cytoskeleton was further demonstrated using cytochalasin D, which displaced Gi
      and impaired muscarinic signaling. We conclude that cytoskeletal integrity is
      required for correct localization and function of Gi-associated signaling
      microdomains.

PMID- 11514590
TI  - Simple epithelium keratins 8 and 18 provide resistance to Fas-mediated apoptosis.
      The protection occurs through a receptor-targeting modulation.
AB  - Keratins 8 and 18 belong to the keratin family of intermediate filament (IF)
      proteins and constitute a hallmark for all simple epithelia, including the liver.
      Hepatocyte IFs are made solely of keratins 8 and 18 (K8/K18). In these cells, the
      loss of one partner via a targeted null mutation in the germline results in
      hepatocytes lacking K8/K18 IFs, thus providing a model of choice for examining
      the function(s) of simple epithelium keratins. Here, we report that K8-null mouse
      hepatocytes in primary culture and in vivo are three- to fourfold more sensitive
      than wild-type (WT) mouse hepatocytes to Fas-mediated apoptosis after stimulation
      with Jo2, an agonistic antibody of Fas ligand. This increased sensitivity is
      associated with a higher and more rapid caspase-3 activation and DNA
      fragmentation. In contrast, no difference in apoptosis is observed between
      cultured K8-null and WT hepatocytes after addition of the Fas-related death
      factors tumor necrosis factor (TNF) alpha or TNF-related apoptosis-inducing
      ligand. Analyses of the Fas distribution in K8-null and WT hepatocytes in culture
      and in situ demonstrate a more prominent targeting of the receptor to the surface
      membrane of K8-null hepatocytes. Moreover, altering Fas trafficking by disrupting
      microtubules with colchicine reduces by twofold the protection generated against
      Jo2-induced lethal action in K8-null versus WT hepatocytes. Together, the results
      strongly suggest that simple epithelium K8/K18 provide resistance to Fas-mediated
      apoptosis and that this protection occurs through a modulation of Fas targeting
      to the cell surface.

PMID- 11514591
TI  - Comparisons of CapG and gelsolin-null macrophages: demonstration of a unique role
      for CapG in receptor-mediated ruffling, phagocytosis, and vesicle rocketing.
AB  - Capping the barbed ends of actin filaments is a critical step for regulating
      actin-based motility in nonmuscle cells. The in vivo function of CapG, a calcium
      sensitive barbed end capping protein and member of the gelsolin/villin family,
      has been assessed using a null Capg allele engineered into mice. Both CapG-null
      mice and CapG/gelsolin double-null mice appear normal and have no gross
      functional abnormalities. However, the loss of CapG in bone marrow macrophages
      profoundly inhibits macrophage colony stimulating factor-stimulated ruffling;
      reintroduction of CapG protein by microinjection fully restores this function.
      CapG-null macrophages also demonstrate approximately 50% impairment of
      immunoglobulin G, and complement-opsonized phagocytosis and lanthanum-induced
      vesicle rocketing. These motile functions are not impaired in gelsolin-null
      macrophages and no additive effects are observed in CapG/gelsolin double-null
      macrophages, establishing that CapG function is distinct from, and does not
      overlap with, gelsolin in macrophages. Our observations indicate that CapG is
      required for receptor-mediated ruffling, and that it is a major functional
      component of macrophage phagocytosis. These primary effects on macrophage motile
      function suggest that CapG may be a useful target for the regulation of
      macrophage-mediated inflammatory responses.

PMID- 11514592
TI  - Impaired skin wound healing in peroxisome proliferator-activated receptor
      (PPAR)alpha and PPARbeta mutant mice.
AB  - We show here that the alpha, beta, and gamma isotypes of peroxisome proliferator
      activated receptor (PPAR) are expressed in the mouse epidermis during fetal
      development and that they disappear progressively from the interfollicular
      epithelium after birth. Interestingly, PPARalpha and beta expression is
      reactivated in the adult epidermis after various stimuli, resulting in
      keratinocyte proliferation and differentiation such as tetradecanoylphorbol
      acetate topical application, hair plucking, or skin wound healing. Using
      PPARalpha, beta, and gamma mutant mice, we demonstrate that PPARalpha and beta
      are important for the rapid epithelialization of a skin wound and that each of
      them plays a specific role in this process. PPARalpha is mainly involved in the
      early inflammation phase of the healing, whereas PPARbeta is implicated in the
      control of keratinocyte proliferation. In addition and very interestingly,
      PPARbeta mutant primary keratinocytes show impaired adhesion and migration
      properties. Thus, the findings presented here reveal unpredicted roles for
      PPARalpha and beta in adult mouse epidermal repair.

PMID- 11514593
TI  - v-Src phosphorylation of connexin 43 on Tyr247 and Tyr265 disrupts gap junctional
      communication.
AB  - The mechanism by which v-Src disrupts connexin (Cx)43 intercellular gap
      junctional communication (GJC) is not clear. In this study, we determined that
      Tyr247 (Y247) and the previously identified Tyr265 (Y265) site of Cx43 were the
      primary phosphorylation targets for activated Src in vitro. We established an in
      vivo experimental system by stably expressing v-Src and wild-type (wt) Cx43, or
      Y247F, Y265F, or Y247F/Y265F Cx43 mutants in a Cx43 knockout mouse cell line. Wt
      and mutant Cx43 localized to the plasma membrane in the absence or presence of v
      Src. When coexpressed with v-Src, the Y247F, Y265F, and Y247F/Y265F Cx43 mutants
      exhibited significantly reduced levels of tyrosine phosphorylation compared with
      wt Cx43, indicating that Y247 and Y265 were phosphorylation targets of v-Src in
      vivo. Most importantly, GJC established by the Y247F, Y265F, and Y247F/Y265F Cx43
      mutants was resistant to disruption by v-Src. Furthermore, we did not find
      evidence for a role for mitogen-activated protein kinase in mediating the
      disruption of GJC by v-Src. We conclude that phosphorylation on Y247 and Y265 of
      Cx43 is responsible for disrupting GJC in these mammalian cells expressing v-Src.

PMID- 11514594
TI  - CRYP-2/cPTPRO is a neurite inhibitory repulsive guidance cue for retinal neurons
      in vitro.
AB  - Receptor protein tyrosine phosphatases (RPTPs) are implicated as regulators of
      axon growth and guidance. Genetic deletions in the fly have shown that type III
      RPTPs are important in axon pathfinding, but nothing is known about their
      function on a cellular level. Previous experiments in our lab have identified a
      type III RPTP, CRYP-2/cPTPRO, specifically expressed during the period of axon
      outgrowth in the chick brain; cPTPRO is expressed in the axons and growth cones
      of retinal and tectal projection neurons. We constructed a fusion protein
      containing the extracellular domain of cPTPRO fused to the Fc portion of mouse
      immunoglobulin G-1, and used it to perform in vitro functional assays. We found
      that the extracellular domain of cPTPRO is an antiadhesive, neurite inhibitory
      molecule for retinal neurons. In addition, cPTPRO had potent growth cone
      collapsing activity in vitro, and locally applied gradients of cPTPRO repelled
      growing retinal axons. This chemorepulsive effect could be regulated by the level
      of cGMP in the growth cone. Immunohistochemical examination of the retina
      indicated that cPTPRO has at least one heterophilic binding partner in the
      retina. Taken together, our results indicate that cPTPRO may act as a guidance
      cue for retinal ganglion cells during vertebrate development.

PMID- 11514595
TI  - Tyrosine cross-linking of extracellular matrix is catalyzed by Duox, a
      multidomain oxidase/peroxidase with homology to the phagocyte oxidase subunit
      gp91phox.
AB  - High molecular weight homologues of gp91phox, the superoxide-generating subunit
      of phagocyte nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase, have
      been identified in human (h) and Caenorhabditis elegans (Ce), and are termed Duox
      for "dual oxidase" because they have both a peroxidase homology domain and a
      gp91phox domain. A topology model predicts that the enzyme will utilize cytosolic
      NADPH to generate reactive oxygen, but the function of the ecto peroxidase domain
      was unknown. Ce-Duox1 is expressed in hypodermal cells underlying the cuticle of
      larval animals. To investigate function, RNA interference (RNAi) was carried out
      in C. elegans. RNAi animals showed complex phenotypes similar to those described
      previously in mutations in collagen biosynthesis that are known to affect the
      cuticle, an extracellular matrix. Electron micrographs showed gross abnormalities
      in the cuticle of RNAi animals. In cuticle, collagen and other proteins are cross
      linked via di- and trityrosine linkages, and these linkages were absent in RNAi
      animals. The expressed peroxidase domains of both Ce-Duox1 and h-Duox showed
      peroxidase activity and catalyzed cross-linking of free tyrosine ethyl ester.
      Thus, Ce-Duox catalyzes the cross-linking of tyrosine residues involved in the
      stabilization of cuticular extracellular matrix.

PMID- 11514596
TI  - Maturation of dendritic cells is accompanied by rapid transcriptional silencing
      of class II transactivator (CIITA) expression.
AB  - Cell surface expression of major histocompatibility complex class II (MHCII)
      molecules is increased during the maturation of dendritic cells (DCs). This
      enhances their ability to present antigen and activate naive CD4(+) T cells. In
      contrast to increased cell surface MHCII expression, de novo biosynthesis of
      MHCII mRNA is turned off during DC maturation. We show here that this is due to a
      remarkably rapid reduction in the synthesis of class II transactivator (CIITA)
      mRNA and protein. This reduction in CIITA expression occurs in human monocyte
      derived DCs and mouse bone marrow-derived DCs, and is triggered by a variety of
      different maturation stimuli, including lipopolysaccharide, tumor necrosis factor
      alpha, CD40 ligand, interferon alpha, and infection with Salmonella typhimurium
      or Sendai virus. It is also observed in vivo in splenic DCs in acute myelin
      oligodendrocyte glycoprotein induced experimental autoimmune encephalitis. The
      arrest in CIITA expression is the result of a transcriptional inactivation of the
      MHC2TA gene. This is mediated by a global repression mechanism implicating
      histone deacetylation over a large domain spanning the entire MHC2TA regulatory
      region.

PMID- 11514597
TI  - Selective abrogation of major histocompatibility complex class II expression on
      extrahematopoietic cells in mice lacking promoter IV of the class II
      transactivator gene.
AB  - MHC class II (MHCII) molecules play a pivotal role in the induction and
      regulation of immune responses. The transcriptional coactivator class II
      transactivator (CIITA) controls MHCII expression. The CIITA gene is regulated by
      three independent promoters (pI, pIII, pIV). We have generated pIV knockout mice.
      These mice exhibit selective abrogation of interferon (IFN)-gamma-induced MHCII
      expression on a wide variety of non-bone marrow-derived cells, including
      endothelia, epithelia, astrocytes, and fibroblasts. Constitutive MHCII expression
      on cortical thymic epithelial cells, and thus positive selection of CD4(+) T
      cells, is also abolished. In contrast, constitutive and inducible MHCII
      expression is unaffected on professional antigen-presenting cells, including B
      cells, dendritic cells, and IFN-gamma-activated cells of the macrophage lineage.
      pIV(-/-) mice have thus allowed precise definition of CIITA pIV usage in vivo.
      Moreover, they represent a unique animal model for studying the significance and
      contribution of MHCII-mediated antigen presentation by nonprofessional antigen
      presenting cells in health and disease.

PMID- 11514598
TI  - Positive selection of CD4(+) T cells is induced in vivo by agonist and inhibited
      by antagonist peptides.
AB  - The nature of peptides that positively select T cells in the thymus remains
      poorly defined. Here we report an in vivo model to study the mechanisms of
      positive selection of CD4(+) T cells. We have restored positive selection of TCR
      transgenic CD4(+) thymocytes, arrested at the CD4(+)CD8(+) stage, due to the lack
      of the endogenously selecting peptide(s), in mice deficient for H2-M and
      invariant chain. A single injection of soluble agonist peptide(s) initiated
      positive selection of CD4(+) transgenic T cells that lasted for up to 14 days.
      Positively selected CD4(+) T cells repopulated peripheral lymphoid organs and
      could respond to the antigenic peptide. Furthermore, coinjection of the
      antagonist peptide significantly inhibited agonist-driven positive selection.
      Hence, contrary to the prevailing view, positive selection of CD4(+) thymocytes
      can be induced in vivo by agonist peptides and may be a result of accumulation of
      signals from TCR engaged by different peptides bound to major histocompatibility
      complex class II molecules. We have also identified a candidate natural agonist
      peptide that induces positive selection of CD4(+) TCR transgenic thymocytes.

PMID- 11514599
TI  - Identification of the transferrin receptor as a novel immunoglobulin (Ig)A1
      receptor and its enhanced expression on mesangial cells in IgA nephropathy.
AB  - The biological functions of immunoglobulin (Ig)A antibodies depend primarily on
      their interaction with cell surface receptors. Four IgA receptors are presently
      characterized. The FcalphaRI (CD89) expressed by myeloid cells selectively binds
      IgA1 and IgA2 antibodies, whereas the poly-IgR, Fcalpha/muR, and
      asialoglycoprotein receptors bind other ligands in addition to IgA. IgA binding
      by mesangial cells, epithelial cells, and proliferating lymphocytes is also well
      documented, but the nature of the IgA receptors on these cells remains elusive. A
      monoclonal antibody (A24) is described here that specifically blocks IgA binding
      to epithelial and B lymphocyte cell lines. Both the A24 antibody and IgA1
      myelomas bind a cell surface protein that is identified as the transferrin
      receptor (CD71). The transferrin receptor selectively binds IgA1 antibodies,
      monomeric better than polymeric forms, and the IgA1 binding is inhibitable by
      transferrin. Transferrin receptor expression is upregulated on cultured mesangial
      cells as well as on glomerular mesangial cells in patients with IgA nephropathy.
      The characterization of transferrin receptor as a novel IgA1 receptor on renal
      mesangial cells suggests its potential involvement in the pathogenesis of IgA
      nephropathy.

PMID- 11514600
TI  - Major histocompatibility complex class II-positive cortical epithelium mediates
      the selection of CD4(+)25(+) immunoregulatory T cells.
AB  - CD4(+)25(+) T cells are a unique population of immunoregulatory T cells which are
      critical for the prevention of autoimmunity. To address the thymic selection of
      these cells we have used two models of attenuated thymic deletion. In K14
      A(beta)(b) mice, major histocompatibility complex (MHC) class II I-A(b)
      expression is limited to thymic cortical epithelium and deletion by hematopoietic
      antigen-presenting cells does not occur. In H2-DMalpha-deficient mice, MHC class
      II molecules contain a limited array of self-peptides resulting in inefficient
      clonal deletion. We find that CD4(+)25(+) T cells are present in the thymus and
      periphery of K14-A(beta)(b) and H2-DMalpha-deficient mice and, like their wild
      type counterparts, suppress the proliferation of cocultured CD4(+)25(-) effector
      T cells. In contrast, CD4(+)25(+) T cells from MHC class II-deficient mice do not
      suppress responder CD4(+) T cells in vitro or in vivo. Thus, development of
      regulatory CD4(+)25(+) T cells is dependent on MHC class II-positive thymic
      cortical epithelium. Furthermore, analysis of the specificities of CD4(+)25(+) T
      cells in K14-A(beta)(b) and H2-DMalpha-deficient mice suggests that a subset of
      CD4(+)25(+) T cells is subject to negative selection on hematopoietic antigen
      presenting cells.

PMID- 11514601
TI  - Requirement for transforming growth factor beta1 in controlling T cell apoptosis.
AB  - Transforming growth factor (TGF)-beta1, a potent immunoregulatory molecule, was
      found to control the life and death decisions of T lymphocytes. Both thymic and
      peripheral T cell apoptosis was increased in mice lacking TGF-beta1 (TGF-beta1(-/
      )) compared with wild-type littermates. Engagement of the T cell receptor
      enhanced this aberrant T cell apoptosis, as did signaling through either the
      death receptor Fas or the tumor necrosis factor alpha receptor in peripheral T
      cells. Strikingly, TGF-beta was localized within the mitochondria of normal T
      cells, and the absence of TGF-beta1 resulted in disruption of mitochondrial
      membrane potential (Deltapsi(m)), which marks the point of no return in a cell
      condemned to die. This TGF-beta-dependent regulation of viability appears
      dissociable from the TGF-beta1 membrane receptor-Smad3 signaling pathway, but
      associated with a mitochondrial antiapoptotic protein Bcl-XL. Thus, TGF-beta1 may
      protect T cells at multiple sites in the death pathway, particularly by
      maintaining the essential integrity of mitochondria. These findings may have
      broad implications not only for T cell selection and death in immune responses
      and in the generation of tolerance, but also for defining the mechanisms of
      programmed cell death in general.

PMID- 11514602
TI  - Interference with immunoglobulin (Ig)alpha immunoreceptor tyrosine-based
      activation motif (ITAM) phosphorylation modulates or blocks B cell development,
      depending on the availability of an Igbeta cytoplasmic tail.
AB  - To determine the function of immunoglobulin (Ig)alpha immunoreceptor tyrosine
      based activation motif (ITAM) phosphorylation, we generated mice in which Igalpha
      ITAM tyrosines were replaced by phenylalanines (Igalpha(FF/FF)). Igalpha(FF/FF)
      mice had a specific reduction of B1 and marginal zone B cells, whereas B2 cell
      development appeared to be normal, except that lambda1 light chain usage was
      increased. The mutants responded less efficiently to T cell-dependent antigens,
      whereas T cell-independent responses were unaffected. Upon B cell receptor
      ligation, the cells exhibited heightened calcium flux, weaker Lyn and Syk
      tyrosine phosphorylation, and phosphorylation of Igalpha non-ITAM tyrosines.
      Strikingly, when the Igalpha ITAM mutation was combined with a truncation of
      Igbeta, B cell development was completely blocked at the pro-B cell stage,
      indicating a crucial role of ITAM phosphorylation in B cell development.

PMID- 11514604
TI  - Elucidating the autoimmune and antitumor effector mechanisms of a treatment based
      on cytotoxic T lymphocyte antigen-4 blockade in combination with a B16 melanoma
      vaccine: comparison of prophylaxis and therapy.
AB  - We have previously shown that small B16 melanomas can be successfully treated
      using a combination of anti-cytotoxic T lymphocyte antigen (CTLA)-4 monoclonal
      antibody with a granulocyte/macrophage colony-stimulating factor (GM-CSF)
      producing irradiated tumor cell vaccine. Regression of tumors results in long
      lasting immunity and is frequently accompanied by autoimmune depigmentation. Here
      we examine the cellular and molecular mechanisms of this combined treatment.
      Histological examination of depigmented lesions revealed infiltration of
      polymorphonuclear cells and deposition of antibody. The combination therapy also
      induced tumor rejection and skin depigmentation in B cell-deficient and in CD4(+)
      T cell-depleted mice. Both effects of the treatment absolutely required CD8(+) T
      cells. Analysis of the response in successfully treated mice revealed elevated
      levels of CD8(+) T cells specific for a nonameric peptide consisting of residues
      180-188 of the melanocyte differentiation antigen tyrosinase-related protein
      (TRP)2. There was no evidence of reactivity to the melanocyte antigens gp100,
      tyrosinase, Mart1/MelanA, or TRP1. Fas-FasL interactions and perforin played a
      role in mounting the effector response, whereas the tumor necrosis factor pathway
      was not required. The cellular requirements for tumor rejection in this
      therapeutic setting were strikingly different from those in a prophylactic
      setting. In particular, if mice received a prophylactic vaccine consisting of
      anti-CTLA-4 and B16-GM-CSF before tumor challenge, full protection was obtained
      even in the absence of CD8(+) T cells. Our data demonstrate that therapeutic
      autoreactive CD8(+) T cell responses can effectively be generated in tumor
      bearing mice and stresses the value of studying tumor immunity in a therapeutic
      rather than a prophylactic setting.

PMID- 11514603
TI  - The role of recombination activating gene (RAG) reinduction in thymocyte
      development in vivo.
AB  - Assembly of T cell receptor (TCR)alpha/beta genes by variable/diversity/joining
      (V[D]J) rearrangement is an ordered process beginning with recombination
      activating gene (RAG) expression and TCRbeta recombination in CD4(-)CD8(-)CD25(+)
      thymocytes. In these cells, TCRbeta expression leads to clonal expansion, RAG
      downregulation, and TCRbeta allelic exclusion. At the subsequent CD4(+)CD8(+)
      stage, RAG expression is reinduced and V(D)J recombination is initiated at the
      TCRalpha locus. This second wave of RAG expression is terminated upon expression
      of a positively selected alpha/beta TCR. To examine the physiologic role of the
      second wave of RAG expression, we analyzed mice that cannot reinduce RAG
      expression in CD4(+)CD8(+) T cells because the transgenic locus that directs RAG1
      and RAG2 expression in these mice is missing a distal regulatory element
      essential for reinduction. In the absence of RAG reinduction we find normal
      numbers of CD4(+)CD8(+) cells but a 50-70% reduction in the number of mature
      CD4(+)CD8(-) and CD4(-)CD8(+) thymocytes. TCRalpha rearrangement is restricted to
      the 5' end of the Jalpha cluster and there is little apparent secondary TCRalpha
      recombination. Comparison of the TCRalpha genes expressed in wild-type or mutant
      mice shows that 65% of all alpha/beta T cells carry receptors that are normally
      assembled by secondary TCRalpha rearrangement. We conclude that RAG reinduction
      in CD4(+)CD8(+) thymocytes is not required for initial TCRalpha recombination but
      is essential for secondary TCRalpha recombination and that the majority of
      TCRalpha chains expressed in mature T cells are products of secondary
      recombination.

PMID- 11514605
TI  - T cell development and T cell responses in mice with mutations affecting
      tyrosines 292 or 315 of the ZAP-70 protein tyrosine kinase.
AB  - After stimulation of the T cell receptor (TCR), the tyrosine residues 292 and 315
      in interdomain B of the protein tyrosine kinase ZAP-70 become phosphorylated and
      plausibly function as docking sites for Cbl and Vav1, respectively. The two
      latter proteins have been suggested to serve as substrates for ZAP-70 and to fine
      tune its function. To address the role of these residues in T cell development
      and in the function of primary T cells, we have generated mice that express ZAP
      70 molecules with Tyr to Phe substitution at position 292 (Y292F) or 315 (Y315F).
      When analyzed in a sensitized TCR transgenic background, the ZAP-70 Y315F
      mutation reduced the rate of positive selection and delayed the occurrence of
      negative selection. Furthermore, this mutation unexpectedly affected the
      constitutive levels of the CD3-zeta p21 phosphoisoform. Conversely, the ZAP-70
      Y292F mutation upregulated proximal events in TCR signaling and allowed more T
      cells to produce interleukin 2 and interferon gamma in response to a given dose
      of antigen. The observation that ZAP-70 Y292F T cells have a slower rate of
      ligand-induced TCR downmodulation suggests that Y292 is likely involved in
      regulating the duration activated TCR reside at the cell surface. Furthermore, we
      showed that Y292 and Y315 are dispensable for the TCR-induced tyrosine
      phosphorylation of Cbl and Vav1, respectively. Therefore, other molecules present
      in the TCR signaling cassette act as additional adaptors for Cbl and Vav1. The
      present in vivo analyses extend previous data based on transformed T cell lines
      and suggest that residue Y292 plays a role in attenuation of TCR signaling,
      whereas residue Y315 enhances ZAP-70 function.

PMID- 11514606
TI  - Requirement for tyrosine residues 315 and 319 within zeta chain-associated
      protein 70 for T cell development.
AB  - Engagement of the T cell antigen receptor (TCR) induces the transphosphorylation
      of the zeta chain-associated protein of 70,000 Mr (ZAP-70) protein tyrosine
      kinase (PTK) by the CD4/8 coreceptor associated Lck PTK. Phosphorylation of Tyr
      493 within ZAP-70's activation loop results in the enzymatic activation of ZAP
      70. Additional tyrosines (Tyrs) within ZAP-70 are phosphorylated that play both
      positive and negative regulatory roles in TCR function. Phosphorylation of Tyr
      residues (Tyrs 315 and 319) within the Interdomain B region of the ZAP-70 PTK
      plays important roles in the generation of second messengers after TCR
      engagement. Here, we demonstrate that phosphorylation of these two Tyr residues
      also play important roles in mediating the positive and negative selection of T
      cells in the thymus.

PMID- 11514607
TI  - Requirement of interleukin 17 receptor signaling for lung CXC chemokine and
      granulocyte colony-stimulating factor expression, neutrophil recruitment, and
      host defense.
AB  - Bacterial pneumonia is an increasing complication of HIV infection and inversely
      correlates with the CD4(+) lymphocyte count. Interleukin (IL)-17 is a cytokine
      produced principally by CD4(+) T cells, which induces granulopoiesis via
      granulocyte colony-stimulating factor (G-CSF) production and induces CXC
      chemokines. We hypothesized that IL-17 receptor (IL-17R) signaling is critical
      for G-CSF and CXC chemokine production and lung host defenses. To test this, we
      used a model of Klebsiella pneumoniae lung infection in mice genetically
      deficient in IL-17R or in mice overexpressing a soluble IL-17R. IL-17R-deficient
      mice were exquisitely sensitive to intranasal K. pneumoniae with 100% mortality
      after 48 h compared with only 40% mortality in controls. IL-17R knockout (KO)
      mice displayed a significant delay in neutrophil recruitment into the alveolar
      space, and had greater dissemination of K. pneumoniae compared with control mice.
      This defect was associated with a significant reduction in steady-state levels of
      G-CSF and macrophage inflammatory protein (MIP)-2 mRNA and protein in the lung in
      response to the K. pneumoniae challenge in IL-17R KO mice. Thus, IL-17R signaling
      is critical for optimal production of G-CSF and MIP-2 and local control of
      pulmonary K. pneumoniae infection. These data support impaired IL-17R signaling
      as a potential mechanism by which deficiency of CD4 lymphocytes predisposes to
      bacterial pneumonia.

PMID- 11514608
TI  - B cell adaptor containing src homology 2 domain (BASH) links B cell receptor
      signaling to the activation of hematopoietic progenitor kinase 1.
AB  - The B cell adaptor containing src homology 2 domain (BASH; also termed BLNK or
      SLP-65), is crucial for B cell antigen receptor (BCR)-mediated activation,
      proliferation, and differentiation of B cells. BCR-mediated tyrosine
      phosphorylation of BASH creates binding sites for signaling effectors such as
      phospholipase Cgamma (PLCgamma)2 and Vav, while the function of its COOH-terminal
      src homology 2 domain is unknown. We have now identified hematopoietic progenitor
      kinase (HPK)1, a STE20-related serine/threonine kinase, as a protein that
      inducibly interacts with the BASH SH2 domain. BCR ligation induced rapid tyrosine
      phosphorylation of HPK1 mainly by Syk and Lyn, resulting in its association with
      BASH and catalytic activation. BCR-mediated activation of HPK1 was impaired in
      Syk- or BASH-deficient B cells. The functional SH2 domain of BASH and Tyr-379
      within HPK1 which we identified as a Syk-phosphorylation site were both necessary
      for interaction of both proteins and efficient HPK1 activation after BCR
      stimulation. Furthermore, HPK1 augmented, whereas its kinase-dead mutant
      inhibited IkappaB kinase beta (IKKbeta) activation by BCR engagement. These
      results reveal a novel BCR signaling pathway leading to the activation of HPK1
      and subsequently IKKbeta, in which BASH recruits tyrosine-phosphorylated HPK1
      into the BCR signaling complex.

PMID- 11514609
TI  - CD47 (integrin-associated protein) engagement of dendritic cell and macrophage
      counterreceptors is required to prevent the clearance of donor
      lymphohematopoietic cells.
AB  - Integrin-associated protein (CD47) is a broadly expressed protein that
      costimulates T cells, facilitates leukocyte migration, and inhibits macrophage
      scavenger function. To determine the role of CD47 in regulating alloresponses,
      CD47(+/+) or CD47(-/-) T cells were infused into irradiated or nonconditioned
      major histocompatibility complex disparate recipients. Graft-versus-host disease
      lethality was markedly reduced with CD47(-/-) T cells. Donor CD47(-/-) T cells
      failed to engraft in immunodeficient allogeneic recipients. CD47(-/-) marrow was
      unable to reconstitute heavily irradiated allogeneic or congenic immune-deficient
      CD47(+/+) recipients. These data suggested that CD47(-/-) T cells and marrow
      cells were cleared by the innate immune system. To address this hypothesis, dye
      labeled CD47(-/-) and CD47(+/+) lymphocytes or marrow cells were infused in vivo
      and clearance was followed. Dye-labeled CD47(-/-) cells were engulfed by splenic
      dendritic cells and macrophages resulting in the clearance of virtually all CD47(
      /-) lymphohematopoietic cells within 1 day after infusion. Host phagocyte
      depleted CD47(+/+) recipients partially accepted allogeneic CD47(-/-) T cells.
      Thus, dendritic cells and macrophages clear lymphohematopoietic cells that have
      downregulated CD47 density. CD47 expression may be a critical indicator for
      determining whether lymphohematopoietic cells will survive or be cleared.

PMID- 11514610
TI  - Requirement for the chemokine receptor CCR6 in allergic pulmonary inflammation.
AB  - Allergic asthmatic responses in the airway are associated with airway
      hyperreactivity, eosinophil accumulation in the lung, and cytokine production by
      allergen-specific, T helper cell type 2 (Th2) lymphocytes. Here, we show that in
      a cockroach antigen (CA) model of allergic pulmonary inflammation, the chemokine
      macrophage inflammatory protein (MIP)-3alpha is expressed in the lung within
      hours of allergen challenge. To determine the biologic relevance of this
      expression, mice lacking CCR6, the only known receptor for MIP-3alpha, were
      studied for their response to CA. CCR6-deficient mice were immunized to the same
      extent as their wild-type counterparts, as judged by cytokine production in
      antigen-challenged lymphocytes. However, compared with CA-challenged wild-type
      mice, challenged CCR6-deficient mice had reduced airway resistance, fewer
      eosinophils around the airway, lower levels of interleukin 5 in the lung, and
      reduced serum levels of immunoglobulin E. Together, these data demonstrate that
      MIP-3alpha and CCR6 function in allergic pulmonary responses and suggest that
      these molecules might represent novel therapeutic targets for treatment of
      asthma.

PMID- 11514611
TI  - The pIV-otal class II transactivator promoter regulates major histocompatibility
      complex class II expression in the thymus.

PMID- 11514612
TI  - T cell death and transforming growth factor beta1.

PMID- 11514613
TI  - Caveolin-1 expression negatively regulates cell cycle progression by inducing
      G(0)/G(1) arrest via a p53/p21(WAF1/Cip1)-dependent mechanism.
AB  - Caveolin-1 is a principal component of caveolae membranes in vivo. Caveolin-1
      mRNA and protein expression are lost or reduced during cell transformation by
      activated oncogenes. Interestingly, the human caveolin-1 gene is localized to a
      suspected tumor suppressor locus (7q31.1). However, it remains unknown whether
      caveolin-1 plays any role in regulating cell cycle progression. Here, we directly
      demonstrate that caveolin-1 expression arrests cells in the G(0)/G(1) phase of
      the cell cycle. We show that serum starvation induces up-regulation of endogenous
      caveolin-1 and arrests cells in the G(0)/G(1) phase of the cell cycle. Moreover,
      targeted down-regulation of caveolin-1 induces cells to exit the G(0)/G(1) phase.
      Next, we constructed a green fluorescent protein-tagged caveolin-1 (Cav-1-GFP) to
      examine the effect of caveolin-1 expression on cell cycle regulation. We directly
      demonstrate that recombinant expression of Cav-1-GFP induces arrest in the
      G(0)/G(1) phase of the cell cycle. To examine whether caveolin-1 expression is
      important for modulating cell cycle progression in vivo, we expressed wild-type
      caveolin-1 as a transgene in mice. Analysis of primary cultures of mouse
      embryonic fibroblasts from caveolin-1 transgenic mice reveals that caveolin-1
      induces 1) cells to exit the S phase of the cell cycle with a concomitant
      increase in the G(0)/G(1) population, 2) a reduction in cellular proliferation,
      and 3) a reduction in the DNA replication rate. Finally, we demonstrate that
      caveolin-1-mediated cell cycle arrest occurs through a p53/p21-dependent pathway.
      Taken together, our results provide the first evidence that caveolin-1 expression
      plays a critical role in the modulation of cell cycle progression in vivo.

PMID- 11514614
TI  - Dynamin-related protein Drp1 is required for mitochondrial division in mammalian
      cells.
AB  - Mutations in the human dynamin-related protein Drp1 cause mitochondria to form
      perinuclear clusters. We show here that these mitochondrial clusters consist of
      highly interconnected mitochondrial tubules. The increased connectivity between
      mitochondria indicates that the balance between mitochondrial division and fusion
      is shifted toward fusion. Such a shift is consistent with a block in
      mitochondrial division. Immunofluorescence and subcellular fractionation show
      that endogenous Drp1 is localized to mitochondria, which is also consistent with
      a role in mitochondrial division. A direct role in mitochondrial division is
      suggested by time-lapse photography of transfected cells, in which green
      fluorescent protein fused to Drp1 is concentrated in spots that mark actual
      mitochondrial division events. We find that purified human Drp1 can self-assemble
      into multimeric ring-like structures with dimensions similar to those of dynamin
      multimers. The structural and functional similarities between dynamin and Drp1
      suggest that Drp1 wraps around the constriction points of dividing mitochondria,
      analogous to dynamin collars at the necks of budding vesicles. We conclude that
      Drp1 contributes to mitochondrial division in mammalian cells.

PMID- 11514615
TI  - Cdc42-dependent modulation of tight junctions and membrane protein traffic in
      polarized Madin-Darby canine kidney cells.
AB  - Polarized epithelial cells maintain the asymmetric composition of their apical
      and basolateral membrane domains by at least two different processes. These
      include the regulated trafficking of macromolecules from the biosynthetic and
      endocytic pathway to the appropriate membrane domain and the ability of the tight
      junction to prevent free mixing of membrane domain-specific proteins and lipids.
      Cdc42, a Rho family GTPase, is known to govern cellular polarity and membrane
      traffic in several cell types. We examined whether this protein regulated tight
      junction function in Madin-Darby canine kidney cells and pathways that direct
      proteins to the apical and basolateral surface of these cells. We used Madin
      Darby canine kidney cells that expressed dominant-active or dominant-negative
      mutants of Cdc42 under the control of a tetracycline-repressible system. Here we
      report that expression of dominant-active Cdc42V12 or dominant-negative Cdc42N17
      altered tight junction function. Expression of Cdc42V12 slowed endocytic and
      biosynthetic traffic, and expression of Cdc42N17 slowed apical endocytosis and
      basolateral to apical transcytosis but stimulated biosynthetic traffic. These
      results indicate that Cdc42 may modulate multiple cellular pathways required for
      the maintenance of epithelial cell polarity.

PMID- 11514616
TI  - A conserved mechanism of synaptogyrin localization.
AB  - We have studied the localization of synaptogyrin family members in vivo. Both
      native and green fluorescent protein (GFP)-tagged Caenorhabditis elegans
      synaptogyrin (SNG-1) are expressed in neurons and synaptically localized.
      Deletion and mutational analysis with the use of GFP-tagged SNG-1 has defined a
      38 amino acid sequence within the C terminus of SNG-1 and a single arginine in
      the cytoplasmic loop between transmembrane domain 2 and 3 that are required for
      SNG-1 localization. These domains may represent components of signals that target
      synaptogyrin for endocytosis from the plasma membrane and direct synaptogyrin to
      synaptic vesicles, respectively. In chimeric studies, these regions were
      sufficient to relocalize cellugyrin, a nonneuronal form of synaptogyrin, from
      nonsynaptic regions such as the sensory dendrites and the cell body to synaptic
      vesicles. Furthermore, GFP-tagged rat synaptogyrin is synaptically localized in
      neurons of C. elegans and in cultured hippocampal neurons. Similarly, the C
      terminal domain of rat synaptogyrin is necessary for localization in hippocampal
      neurons. Our study suggests that the mechanisms for synaptogyrin localization are
      likely to be conserved from C. elegans to vertebrates.

PMID- 11514617
TI  - Focal adhesion kinase and p130Cas mediate both sarcomeric organization and
      activation of genes associated with cardiac myocyte hypertrophy.
AB  - Hypertrophic terminally differentiated cardiac myocytes show increased sarcomeric
      organization and altered gene expression. Previously, we established a role for
      the nonreceptor tyrosine kinase Src in signaling cardiac myocyte hypertrophy.
      Here we report evidence that p130Cas (Cas) and focal adhesion kinase (FAK)
      regulate this process. In neonatal cardiac myocytes, tyrosine phosphorylation of
      Cas and FAK increased upon endothelin (ET) stimulation. FAK, Cas, and paxillin
      were localized in sarcomeric Z-lines, suggesting that the Z-line is an important
      signaling locus in these cells. Cas, alone or in cooperation with Src, modulated
      basal and ET-stimulated atrial natriuretic peptide (ANP) gene promoter activity,
      a marker of cardiac hypertrophy. Expression of the C-terminal focal adhesion
      targeting domain of FAK interfered with localization of endogenous FAK to Z
      lines. Expression of the Cas-binding proline-rich region 1 of FAK hindered
      association of Cas with FAK and impaired the structural stability of sarcomeres.
      Collectively, these results suggest that interaction of Cas with FAK, together
      with their localization to Z-lines, is critical to assembly of sarcomeric units
      in cardiac myocytes in culture. Moreover, expression of the focal adhesion
      targeting and/or the Cas-binding proline-rich regions of FAK inhibited ANP
      promoter activity and suppressed ET-induced ANP and brain natriuretic peptide
      gene expression. In summary, assembly of signaling complexes that include the
      focal adhesion proteins Cas, FAK, and paxillin at Z-lines in the cardiac myocyte
      may regulate, either directly or indirectly, both cytoskeletal organization and
      gene expression associated with cardiac myocyte hypertrophy.

PMID- 11514618
TI  - Biogenesis of Golgi stacks in imaginal discs of Drosophila melanogaster.
AB  - We provide a detailed description of Golgi stack biogenesis that takes place in
      vivo during one of the morphogenetic events in the lifespan of Drosophila
      melanogaster. In early third-instar larvae, small clusters consisting mostly of
      vesicles and tubules were present in epithelial imaginal disk cells. As larvae
      progressed through mid- and late-third instar, these larval clusters became
      larger but also increasingly formed cisternae, some of which were stacked. In
      white pupae, the typical Golgi stack was observed. We show that larval clusters
      are Golgi stack precursors by 1) localizing various Golgi-specific markers to the
      larval clusters by electron and immunofluorescence confocal microscopy, 2)
      driving this conversion in wild-type larvae incubated at 37 degrees C for 2 h,
      and 3) showing that this conversion does not take place in an NSF1 mutant (comt
      17). The biological significance of this conversion became clear when we found
      that the steroid hormone 20-hydroxyecdysone (ecdysone) is critically involved in
      this conversion. In its absence, Golgi stack biogenesis did not occur and the
      larval clusters remained unaltered. We showed that dGM130 and sec23p expression
      increases approximately three- and fivefold, respectively, when discs are exposed
      to ecdysone in vivo and in vitro. Taken together, these results suggest that we
      have developed an in vivo system to study the ecdysone-triggered Golgi stack
      biogenesis.

PMID- 11514619
TI  - Nuclear relocalization of the pre-mRNA splicing factor PSF during apoptosis
      involves hyperphosphorylation, masking of antigenic epitopes, and changes in
      protein interactions.
AB  - The spatial nuclear organization of regulatory proteins often reflects their
      functional state. PSF, a factor essential for pre-mRNA splicing, is visualized by
      the B92 mAb as discrete nuclear foci, which disappeared during apoptosis. Because
      this mode of cell death entails protein degradation, it was considered that PSF,
      which like other splicing factors is sensitive to proteolysis, might be degraded.
      Nonetheless, during the apoptotic process, PSF remained intact and was N
      terminally hyperphosphorylated on serine and threonine residues. Retarded gel
      migration profiles suggested differential phosphorylation of the molecule in
      mitosis vs. apoptosis and under-phosphorylation during blockage of cells at G1/S.
      Experiments with the use of recombinant GFP-tagged PSF provided evidence that in
      the course of apoptosis the antigenic epitopes of PSF are masked and that PSF
      reorganizes into globular nuclear structures. In apoptotic cells, PSF dissociated
      from PTB and bound new partners, including the U1--70K and SR proteins and
      therefore may acquire new functions.

PMID- 11514620
TI  - Mutant rab8 Impairs docking and fusion of rhodopsin-bearing post-Golgi membranes
      and causes cell death of transgenic Xenopus rods.
AB  - Rab8 is a GTPase involved in membrane trafficking. In photoreceptor cells, rab8
      is proposed to participate in the late stages of delivery of rhodopsin-containing
      post-Golgi membranes to the plasma membrane near the base of the connecting
      cilium. To test the function of rab8 in vivo, we generated transgenic Xenopus
      laevis expressing wild-type, constitutively active (Q67L), and dominant negative
      (T22N) forms of canine rab8 in their rod photoreceptors as green fluorescent
      protein (GFP) fusion proteins. Wild-type and constitutively active GFP-rab8
      proteins were primarily associated with Golgi and post-Golgi membranes, whereas
      the dominant negative protein was primarily cytoplasmic. Expression of wild-type
      GFP-rab8 had minimal effects on cell survival and intracellular structures. In
      contrast, GFP-rab8T22N caused rapid retinal degeneration. In surviving peripheral
      rods, tubulo-vesicular structures accumulated at the base of the connecting
      cilium. Expression of GFP-rab8Q67L induced a slower retinal degeneration in some
      tadpoles. Transgene effects were transmitted to F1 offspring. Expression of the
      GFP-rab8 fusion proteins appears to decrease the levels of endogenous rab8
      protein. Our results demonstrate a role for rab8 in docking of post-Golgi
      membranes in rods, and constitute the first report of a transgenic X. laevis
      model of retinal degenerative disease.

PMID- 11514621
TI  - Dominant negative c-jun inhibits activation of the cyclin D1 and cyclin E kinase
      complexes.
AB  - The AP-1 transcription factor is activated by oncogenic signal transduction
      cascades and its function is critical for both mitogenesis and carcinogenesis. To
      define the role of AP-1 in the context of a human fibrosarcoma cell line, HT1080,
      we expressed a dominant negative c-jun mutant fused to the green fluorescent
      protein in an ecdysone-inducible system. We demonstrated that high levels of this
      mutant, GFP-TAM67, inhibit AP-1 activity and arrest cells predominantly in the G1
      phase of the cell cycle. This arrest is reversible and occurs only above a
      threshold concentration; low to moderate levels of GFP-TAM67 are insufficient for
      growth arrest. Contrary to expectations based on the literature, GFP-TAM67 does
      not inhibit expression of cyclin D1, cyclin E, or their respective cyclin
      dependent kinases. However, pRB is hypophosphorylated in GFP-TAM67-arrested cells
      and the activity of both the cyclin D1:cdk and the cyclin E:cdk complexes are
      impaired. Both of these complexes show an increased association with
      p21(CIP1/WAF1), concomitantly with induction of the p21 mRNA by GFP-TAM67. These
      results suggest a novel function of AP-1 in the activation of the G1 cyclin:cdk
      complexes in human tumor cells by regulating the expression of the p21(CIP1/WAF1)
      gene.

PMID- 11514622
TI  - Regulated degradation of an endoplasmic reticulum membrane protein in a tubular
      lysosome in Leishmania mexicana.
AB  - The cell surface of the human parasite Leishmania mexicana is coated with
      glycosylphosphatidylinositol (GPI)-anchored macromolecules and free GPI
      glycolipids. We have investigated the intracellular trafficking of green
      fluorescent protein- and hemagglutinin-tagged forms of dolichol-phosphate-mannose
      synthase (DPMS), a key enzyme in GPI biosynthesis in L. mexicana promastigotes.
      These functionally active chimeras are found in the same subcompartment of the
      endoplasmic reticulum (ER) as endogenous DPMS but are degraded as logarithmically
      growing promastigotes reach stationary phase, coincident with the down-regulation
      of endogenous DPMS activity and GPI biosynthesis in these cells. We provide
      evidence that these chimeras are constitutively transported to and degraded in a
      novel multivesicular tubule (MVT) lysosome. This organelle is a terminal
      lysosome, which is labeled with the endocytic marker FM 4-64, contains lysosomal
      cysteine and serine proteases and is disrupted by lysomorphotropic agents.
      Electron microscopy and subcellular fractionation studies suggest that the DPMS
      chimeras are transported from the ER to the lumen of the MVT via the Golgi
      apparatus and a population of 200-nm multivesicular bodies. In contrast, soluble
      ER proteins are not detectably transported to the MVT lysosome in either log or
      stationary phase promastigotes. Finally, the increased degradation of the DPMS
      chimeras in stationary phase promastigotes coincides with an increase in the
      lytic capacity of the MVT lysosome and changes in the morphology of this
      organelle. We conclude that lysosomal degradation of DPMS may be important in
      regulating the cellular levels of this enzyme and the stage-dependent
      biosynthesis of the major surface glycolipids of these parasites.

PMID- 11514623
TI  - Filopodial initiation and a novel filament-organizing center, the focal ring.
AB  - This study examines filopodial initiation and implicates a putative actin
      filament organizer, the focal ring. Filopodia were optically recorded as they
      emerged from veils, the active lamellar extensions of growth cones. Motile
      histories revealed three events that consistently preceded filopodial emergence:
      an influx of cytoplasm into adjacent filopodia, a focal increase in phase density
      at veil margins, and protrusion of nubs that transform into filopodia. The
      cytoplasmic influx probably supplies materials needed for initiation. In
      correlated time lapse-immunocytochemistry, these focal phase densities
      corresponded to adhesions. These adhesions persisted at filopodial bases,
      regardless of subsequent movements. In correlated time lapse-electron microscopy,
      these adhesion sites contained a focal ring (an oblate, donut-shaped structure
      approximately 120 nm in diameter) with radiating actin filaments. Filament
      geometry may explain filopodial emergence at 30 degree angles relative to
      adjacent filopodia. A model is proposed in which focal rings play a vital role in
      initiating and stabilizing filopodia: 1) they anchor actin filaments at
      adhesions, thereby facilitating tension development and filopodial emergence; 2)
      "axial" filaments connect focal rings to nub tips, thereby organizing filament
      bundling and ensuring the bundle intersects an adhesion; and 3) "lateral"
      filaments interconnect focal rings and filament bundles, thereby helping
      stabilize lamellar margins and filopodia.

PMID- 11514624
TI  - Sac1 lipid phosphatase and Stt4 phosphatidylinositol 4-kinase regulate a pool of
      phosphatidylinositol 4-phosphate that functions in the control of the actin
      cytoskeleton and vacuole morphology.
AB  - Synthesis and turnover of phosphoinositides are tightly regulated processes
      mediated by a set of recently identified kinases and phosphatases. We analyzed
      the primary role of the phosphoinositide phosphatase Sac1p in Saccharomyces
      cerevisiae with the use of a temperature-sensitive allele of this gene. Our
      analysis demonstrates that inactivation of Sac1p leads to a specific increase in
      the cellular levels of phosphatidylinositol 4-phosphate (PtdIns(4)P), accompanied
      by changes in vacuole morphology and an accumulation of lipid droplets. We have
      found that the majority of Sac1p localizes to the endoplasmic reticulum, and this
      localization is crucial for the efficient turnover of PtdIns(4)P. By generating
      double mutant strains harboring the sac1(ts) allele and one of two temperature
      sensitive PtdIns 4-kinase genes, stt4(ts) or pik1(ts), we have demonstrated that
      the bulk of PtdIns(4)P that accumulates in sac1 mutant cells is generated by the
      Stt4 PtdIns 4-kinase, and not Pik1p. Consistent with these findings, inactivation
      of Sac1p partially rescued defects associated with stt4(ts) but not pik1(ts)
      mutant cells. To analyze potential overlapping functions between Sac1p and other
      homologous phosphoinositide phosphatases, sac1(ts) mutant cells lacking various
      other synaptojanin-like phosphatases were generated. These double and triple
      mutants exacerbated the accumulation of intracellular phosphoinositides and
      caused defects in Golgi function. Together, our results demonstrate that Sac1p
      primarily turns over Stt4p-generated PtdIns(4)P and that the membrane
      localization of Sac1p is important for its function in vivo. Regulation of this
      PtdIns(4)P pool appears to be crucial for the maintenance of vacuole morphology,
      regulation of lipid storage, Golgi function, and actin cytoskeleton organization.

PMID- 11514625
TI  - Werner's syndrome protein is required for correct recovery after replication
      arrest and DNA damage induced in S-phase of cell cycle.
AB  - Werner's syndrome (WS) is a rare autosomal recessive disorder that arises as a
      consequence of mutations in a gene coding for a protein that is a member of RecQ
      family of DNA helicases, WRN. The cellular function of WRN is still unclear, but
      on the basis of the cellular phenotypes of WS and of RecQ yeast mutants, its
      possible role in controlling recombination and/or in maintenance of genomic
      integrity during S-phase has been envisaged. With the use of two drugs,
      camptothecin and hydroxyurea, which produce replication-associated DNA damage
      and/or inhibit replication fork progression, we find that WS cells have a slower
      rate of repair associated with DNA damage induced in the S-phase and a reduced
      induction of RAD51 foci. As a consequence, WS cells undergo apoptotic cell death
      more than normal cells, even if they arrest and resume DNA synthesis at an
      apparently normal rate. Furthermore, we report that WS cells show a higher
      background level of DNA strand breaks and an elevated spontaneous induction of
      RAD51 foci. Our findings support the hypothesis that WRN could be involved in the
      correct resolution of recombinational intermediates that arise from replication
      arrest due to either DNA damage or replication fork collapse.

PMID- 11514626
TI  - The proteasomal substrate Stm1 participates in apoptosis-like cell death in
      yeast.
AB  - We have identified the yeast gene STM1 in an overexpression screen for new
      proteasomal substrates. Stm1 is unstable in wild-type cells and stabilized in
      cells with defective proteasomal activity and thus a bona fide substrate of the
      proteasome. It is localized in the perinuclear region and is required for growth
      in the presence of mutagens. Overexpression in cells with impaired proteasomal
      degradation leads to cell death accompanied with cytological markers of
      apoptosis: loss of plasma membrane asymmetry, chromatin condensation, and DNA
      cleavage. Cells lacking Stm1 display deficiency in the apoptosis-like cell death
      process induced by treatment with low concentrations of H(2)O(2). We suggest that
      Stm1 is involved in the control of the apoptosis-like cell death in yeast.
      Survival is increased when Stm1 is completely missing from the cells or when
      inhibition of Stm1 synthesis permits proteasomal degradation to decrease its
      amount in the cell. Conversely, Stm1 accumulation induces cell death. In addition
      we identified five other genes whose overexpression in proteasomal mutants caused
      similar apoptotic phenotypes.

PMID- 11514627
TI  - Amino acid substitutions of coiled-coil protein Tpr abrogate anchorage to the
      nuclear pore complex but not parallel, in-register homodimerization.
AB  - Tpr is a protein component of nuclear pore complex (NPC)-attached intranuclear
      filaments. Secondary structure predictions suggest a bipartite structure, with a
      large N-terminal domain dominated by heptad repeats (HRs) typical for coiled-coil
      -forming proteins. Proposed functions for Tpr have included roles as a homo- or
      heteropolymeric architectural element of the nuclear interior. To gain insight
      into Tpr's ultrastructural properties, we have studied recombinant Tpr segments
      by circular dichroism spectroscopy, chemical cross-linking, and rotary shadowing
      electron microscopy. We show that polypeptides of the N-terminal domain
      homodimerize in vitro and represent alpha-helical molecules of extended rod-like
      shape. With the use of a yeast two-hybrid approach, arrangement of the coiled
      coil is found to be in parallel and in register. To clarify whether Tpr can self
      assemble further into homopolymeric filaments, the full-length protein and
      deletion mutants were overexpressed in human cells and then analyzed by confocal
      immunofluorescence microscopy, cell fractionation, and immuno-electron
      microscopy. Surplus Tpr, which does not bind to the NPC, remains in a soluble
      state of approximately 7.5 S and occasionally forms aggregates of entangled
      molecules but neither self-assembles into extended linear filaments nor stably
      binds to other intranuclear structures. Binding to the NPC is shown to depend on
      the integrity of individual HRs; amino acid substitutions within these HRs
      abrogate NPC binding and render the protein soluble but do not abolish Tpr's
      general ability to homodimerize. Possible contributions of Tpr to the structural
      organization of the nuclear periphery in somatic cells are discussed.

PMID- 11514628
TI  - Targeting of Shiga toxin B-subunit to retrograde transport route in association
      with detergent-resistant membranes.
AB  - In HeLa cells, Shiga toxin B-subunit is transported from the plasma membrane to
      the endoplasmic reticulum, via early endosomes and the Golgi apparatus,
      circumventing the late endocytic pathway. We describe here that in cells derived
      from human monocytes, i.e., macrophages and dendritic cells, the B-subunit was
      internalized in a receptor-dependent manner, but retrograde transport to the
      biosynthetic/secretory pathway did not occur and part of the internalized protein
      was degraded in lysosomes. These differences correlated with the observation that
      the B-subunit associated with Triton X-100-resistant membranes in HeLa cells, but
      not in monocyte-derived cells, suggesting that retrograde targeting to the
      biosynthetic/secretory pathway required association with specialized microdomains
      of biological membranes. In agreement with this hypothesis we found that in HeLa
      cells, the B-subunit resisted extraction by Triton X-100 until its arrival in the
      target compartments of the retrograde pathway, i.e., the Golgi apparatus and the
      endoplasmic reticulum. Furthermore, destabilization of Triton X-100-resistant
      membranes by cholesterol extraction potently inhibited B-subunit transport from
      early endosomes to the trans-Golgi network, whereas under the same conditions,
      recycling of transferrin was not affected. Our data thus provide first evidence
      for a role of lipid asymmetry in membrane sorting at the interface between early
      endosomes and the trans-Golgi network.

PMID- 11514629
TI  - Conditional mutations in gamma-tubulin reveal its involvement in chromosome
      segregation and cytokinesis.
AB  - gamma-Tubulin is a conserved essential protein required for assembly and function
      of the mitotic spindle in humans and yeast. For example, human gamma-tubulin can
      replace the gamma-tubulin gene in Schizosaccharomyces pombe. To understand the
      structural/functional domains of gamma-tubulin, we performed a systematic alanine
      scanning mutagenesis of human gamma-tubulin (TUBG1) and studied phenotypes of
      each mutant allele in S. pombe. Our screen, both in the presence and absence of
      the endogenous S. pombe gamma-tubulin, resulted in 11 lethal mutations and 12
      cold-sensitive mutations. Based on structural mapping onto a homology model of
      human gamma-tubulin generated by free energy minimization, all deleterious
      mutations are found in residues predicted to be located on the surface, some in
      positions to interact with alpha- and/or beta-tubulins in the microtubule
      lattice. As expected, one class of tubg1 mutations has either an abnormal
      assembly or loss of the mitotic spindle. Surprisingly, a subset of mutants with
      abnormal spindles does not arrest in M phase but proceeds through anaphase
      followed by abnormal cytokinesis. These studies reveal that in addition to its
      previously appreciated role in spindle microtubule nucleation, gamma-tubulin is
      involved in the coordination of postmetaphase events, anaphase, and cytokinesis.

PMID- 11514630
TI  - Targeting of a tail-anchored protein to endoplasmic reticulum and mitochondrial
      outer membrane by independent but competing pathways.
AB  - Many mitochondrial outer membrane (MOM) proteins have a transmembrane domain near
      the C terminus and an N-terminal cytosolic moiety. It is not clear how these tail
      anchored (TA) proteins posttranslationally select their target, but C-terminal
      charged residues play an important role. To investigate how discrimination
      between MOM and endoplasmic reticulum (ER) occurs, we used mammalian cytochrome
      b(5), a TA protein existing in two, MOM or ER localized, versions. Substitution
      of the seven C-terminal residues of the ER isoform or of green fluorescent
      protein reporter constructs with one or two arginines resulted in MOM-targeted
      proteins, whereas a single C-terminal threonine caused promiscuous localization.
      To investigate whether targeting to MOM occurs from the cytosol or after transit
      through the ER, we tagged a MOM-directed construct with a C-terminal N
      glycosylation sequence. Although in vitro this construct was efficiently
      glycosylated by microsomes, the protein expressed in vivo localized almost
      exclusively to MOM, and was nearly completely unglycosylated. The small fraction
      of glycosylated protein was in the ER and was not a precursor to the
      unglycosylated form. Thus, targeting occurs directly from the cytosol. Moreover,
      ER and MOM compete for the same polypeptide, explaining the dual localization of
      some TA proteins.

PMID- 11514632
TI  - Cnm67p is a spacer protein of the Saccharomyces cerevisiae spindle pole body
      outer plaque.
AB  - In Saccharomyces cerevisiae, the spindle pole body (SPB) is the functional
      homolog of the mammalian centrosome, responsible for the organization of the
      tubulin cytoskeleton. Cytoplasmic (astral) microtubules essential for the proper
      segregation of the nucleus into the daughter cell are attached at the outer
      plaque on the SPB cytoplasmic face. Previously, it has been shown that Cnm67p is
      an integral component of this structure; cells deleted for CNM67 are lacking the
      SPB outer plaque and thus experience severe nuclear migration defects. With the
      use of partial deletion mutants of CNM67, we show that the N- and C-terminal
      domains of the protein are important for nuclear migration. The C terminus, not
      the N terminus, is essential for Cnm67p localization to the SPB. On the other
      hand, only the N terminus is subject to protein phosphorylation of a yet unknown
      function. Electron microscopy of SPB serial thin sections reveals that deletion
      of the N- or C-terminal domains disturbs outer plaque formation, whereas
      mutations in the central coiled-coil domain of Cnm67p change the distance between
      the SPB core and the outer plaque. We conclude that Cnm67p is the protein that
      connects the outer plaque to the central plaque embedded in the nuclear envelope,
      adjusting the space between them by the length of its coiled-coil.

PMID- 11514631
TI  - Bud8p and Bud9p, proteins that may mark the sites for bipolar budding in yeast.
AB  - The bipolar budding pattern of a/alpha Saccharomyces cerevisiae cells appears to
      depend on persistent spatial markers in the cell cortex at the two poles of the
      cell. Previous analysis of mutants with specific defects in bipolar budding
      identified BUD8 and BUD9 as potentially encoding components of the markers at the
      poles distal and proximal to the birth scar, respectively. Further genetic
      analysis reported here supports this hypothesis. Mutants deleted for BUD8 or BUD9
      grow normally but bud exclusively from the proximal and distal poles,
      respectively, and the double-mutant phenotype suggests that the bipolar budding
      pathway has been totally disabled. Moreover, overexpression of these genes can
      cause either an increased bias for budding at the distal (BUD8) or proximal
      (BUD9) pole or a randomization of bud position, depending on the level of
      expression. The structures and localizations of Bud8p and Bud9p are also
      consistent with their postulated roles as cortical markers. Both proteins appear
      to be integral membrane proteins of the plasma membrane, and they have very
      similar overall structures, with long N-terminal domains that are both N- and O
      glycosylated followed by a pair of putative transmembrane domains surrounding a
      short hydrophilic domain that is presumably cytoplasmic. The putative
      transmembrane and cytoplasmic domains of the two proteins are very similar in
      sequence. When Bud8p and Bud9p were localized by immunofluorescence and tagging
      with GFP, each protein was found predominantly in the expected location, with
      Bud8p at presumptive bud sites, bud tips, and the distal poles of daughter cells
      and Bud9p at the necks of large-budded cells and the proximal poles of daughter
      cells. Bud8p localized approximately normally in several mutants in which
      daughter cells are competent to form their first buds at the distal pole, but it
      was not detected in a bni1 mutant, in which such distal-pole budding is lost.
      Surprisingly, Bud8p localization to the presumptive bud site and bud tip also
      depends on actin but is independent of the septins.

PMID- 11514633
TI  - Actin polymerization is essential for pollen tube growth.
AB  - Actin microfilaments, which are prominent in pollen tubes, have been implicated
      in the growth process; however, their mechanism of action is not well understood.
      In the present work we have used profilin and DNAse I injections, as well as
      latrunculin B and cytochalasin D treatments, under quantitatively controlled
      conditions, to perturb actin microfilament structure and assembly in an attempt
      to answer this question. We found that a approximately 50% increase in the total
      profilin pool was necessary to half-maximally inhibit pollen tube growth, whereas
      a approximately 100% increase was necessary for half-maximal inhibition of
      cytoplasmic streaming. DNAse I showed a similar inhibitory activity but with a
      threefold more pronounced effect on growth than streaming. Latrunculin B, at only
      1--4 nM in the growth medium, has a similar proportion of inhibition of growth
      over streaming to that of profilin. The fact that tip growth is more sensitive
      than streaming to the inhibitory substances and that there is no correlation
      between streaming and growth rates suggests that tip growth requires actin
      assembly in a process independent of cytoplasmic streaming.

PMID- 11514634
TI  - Polyubiquitination is required for US11-dependent movement of MHC class I heavy
      chain from endoplasmic reticulum into cytosol.
AB  - The human cytomegalovirus protein US11 induces the dislocation of MHC class I
      heavy chains from the endoplasmic reticulum (ER) into the cytosol for degradation
      by the proteasome. With the use of a fractionated, permeabilized cell system, we
      find that US11 activity is needed only in the cell membranes and that additional
      cytosolic factors are required for heavy chain dislocation. We identify ubiquitin
      as one of the required cytosolic factors. Cytosol depleted of ubiquitin does not
      support heavy chain dislocation from the ER, and activity can be restored by
      adding back purified ubiquitin. Methylated-ubiquitin or a ubiquitin mutant
      lacking all lysine residues does not substitute for wild-type ubiquitin,
      suggesting that polyubiquitination is required for US11-dependent dislocation. We
      propose a new function for ubiquitin in which polyubiquitination prevents the
      lumenal domain of the MHC class I heavy chain from moving back into the ER lumen.
      A similar mechanism may be operating in the dislocation of misfolded proteins
      from the ER in the cellular quality control pathway.

PMID- 11514636
TI  - An update on estrogen: higher cognitive function, receptor mapping, neurotrophic
      effects.

PMID- 11514637
TI  - Applying Bradford Hill's criteria for causation to neuropsychiatry: challenges
      and opportunities.
AB  - Establishing an argument of causation is an important research activity with
      major clinical and scientific implications. Sir Austin Bradford Hill proposed
      criteria to establish such an argument. These criteria include the strength of
      the association, consistency, specificity, temporal sequence, biological
      gradient, biologic rationale, coherence, experimental evidence, and analogous
      evidence. These criteria are reviewed with the goal of facilitating an increase
      in rigor for establishing arguments of causation in neuropsychiatry. The
      challenges and opportunities related to these criteria in neuropsychiatry are
      reviewed, as are two important arguments for causation: one for poststroke
      depression and one for brain injury as a cause of psychiatric disorders.

PMID- 11514635
TI  - Proteasome inhibitors block a late step in lysosomal transport of selected
      membrane but not soluble proteins.
AB  - The ubiquitin-proteasome pathway acts as a regulator of the endocytosis of
      selected membrane proteins. Recent evidence suggests that it may also function in
      the intracellular trafficking of membrane proteins. In this study, several models
      were used to address the role of the ubiquitin-proteasome pathway in sorting of
      internalized proteins to the lysosome. We found that lysosomal degradation of
      ligands, which remain bound to their receptors within the endocytic pathway, is
      blocked in the presence of specific proteasome inhibitors. In contrast, a ligand
      that dissociates from its receptor upon endosome acidification is degraded under
      the same conditions. Quantitative electron microscopy showed that neither the
      uptake nor the overall distribution of the endocytic marker bovine serum albumin
      gold is substantially altered in the presence of a proteasome inhibitor. The data
      suggest that the ubiquitin-proteasome pathway is involved in an endosomal sorting
      step of selected membrane proteins to lysosomes, thereby providing a mechanism
      for regulated degradation.

PMID- 11514638
TI  - Effects of stimulants on the continuous performance test (CPT): implications for
      CPT use and interpretation.
AB  - An increasing number of treatment plans for individuals with attention
      deficit/hyperactivity disorder (ADHD), as well as other disorders, include
      stimulant medication. The purpose of this study was to investigate the effects of
      stimulant medications on attention and impulsivity as measured by continuous
      performance tests (CPTs). The effect of other stimulants (e.g., caffeine,
      nicotine) on CPT performance was examined as well. Although various versions of
      the CPT were used in the studies reviewed, the research supports improvements in
      CPT performance with stimulant treatment. Implications for the use of CPTs in
      evaluating the effects of medications on attention are discussed. Also presented
      are implications for control of common substances like nicotine or caffeine when
      CPT is used and interpreted as a measure of attention.

PMID- 11514639
TI  - The relationship of akathisia with suicidality and depersonalization among
      patients with schizophrenia.
AB  - An association of suicidality and depersonalization with akathisia has been
      reported, but it is not clear whether these phenomena are specific to akathisia
      or are nonspecific manifestations of distress. The authors used the Barnes
      Akathisia Rating Scale, Brief Psychiatric Rating Scale, and Hamilton Rating Scale
      for Depression (Ham-D) to examine the relationships between suicidality,
      depersonalization, dysphoria, and akathisia in 68 patients with schizophrenia or
      schizophreniform disorder. Akathisia was associated with higher scores on the Ham
      D ratings of suicidality, depersonalization, and agitation. In a logistic
      regression model, depressive mood and subjective awareness of akathisia appeared
      to be the only predictors of suicidality and depersonalization, respectively.
      These findings support the association between akathisia and both suicidality and
      depersonalization. However, these symptoms appear to be nonspecific responses to
      accompanying depressive mood and the subjective awareness of the akathisia
      syndrome, respectively.

PMID- 11514640
TI  - Effects of depression on working memory in presymptomatic Huntington's disease.
AB  - Cognitive decline may precede motor symptoms in Huntington's disease (HD).
      Depression is common in HD and has also been linked with cognitive impairment.
      The contribution of depression to cognition in individuals presymptomatic for HD
      (N=15) was investigated. Tests from the Cambridge Automated Neuropsychological
      Assessment Battery measured visual and working memory. Depression was assessed
      with the Beck Depression Inventory and the Unified Huntington's Disease Rating
      Scale. Depressed mood and estimated time to disease onset, calculated by using
      DNA mutation length, both were significant predictors of working memory
      performance. Findings are consistent with and contribute to existing research
      with individuals presymptomatic for HD, identifying a potentially remediable
      contribution to cognitive decline (i.e., depressed mood).

PMID- 11514641
TI  - Emergent neuroleptic hypersensitivity as a herald of presenile dementia.
AB  - Neuroleptic hypersensitivity is characteristic of dementia with Lewy bodies (DLB)
      but not of other dementias. The authors report 5 patients with psychotic mood
      disorders and long-standing antipsychotic drug therapy. As they reached 50 to 60
      years of age, they unexpectedly developed hypersensitivity to these medications,
      with rigidity, muteness, or the neuroleptic malignant syndrome. Nearly coincident
      with this reaction, they developed progressive cognitive deficits consistent with
      frontotemporal dementia. These patients illustrate emergent neuroleptic
      hypersensitivity as an early manifestation of other dementias. The predisposition
      to neuroleptic hypersensitivity could result from depleted nigral dopaminergic
      neurons suggested by "smudging" of the substantia nigra pars compacta on magnetic
      resonance imaging.

PMID- 11514642
TI  - Aggression in elderly schizophrenia patients: a comparison of nursing home and
      state hospital residents.
AB  - This study examined the role of cognitive functioning, adaptive functioning, and
      symptomatology in predicting aggression in institutionalized geriatric
      schizophrenic patients residing in either a state institution (n=56) or a nursing
      home (n=113). Patients were assessed with a neuropsychological battery and rated
      for positive and negative symptoms, social functioning, and aggressiveness.
      Nursing home residents were older and more cognitively and functionally impaired
      than institutional residents. The prevalence of verbal, but not physical,
      aggression was similar to findings in younger, acutely hospitalized patients in
      previous studies. In the hospitalized group, severity of negative symptoms was
      predictive of physical aggression. In the nursing home group, severity of
      positive symptoms was predictive of verbal aggression and self-care deficit was
      predictive of physical aggression. Results indicate that verbal aggression, like
      positive symptoms, decreases little with aging in institutionalized schizophrenic
      patients, and that predictors of aggressive behavior are as difficult to identify
      in elderly patients as in younger ones.

PMID- 11514643
TI  - Nondominant hemisphere lesions and conversion nonepileptic seizures.
AB  - To explore the hypothesis that lateralized hemispheric dysfunction may contribute
      to the development of conversion symptoms, the authors studied frequency of
      unilateral cerebral physiological or structural abnormalities in 79 consecutive
      patients with conversion nonepileptic seizures (C-NES), who were also compared
      with two groups of epilepsy patients without C-NES. Sixty (76%) of the C-NES
      patients had unilateral cerebral abnormalities on neuroimaging, of which 85% were
      structural. Ictal or interictal epileptiform abnormalities on EEG were found in
      78% of C-NES patients and focal slowing in another 10%. Fifty (63%) of the C-NES
      patients had both structural and epileptiform abnormalities. Among the 60 with
      unilateral abnormalities, 43 (71%) had right hemisphere structural lesions or
      physiologic dysfunctions (C-NES>non-C-NES, P<0.02). This study supports prior
      studies and clinical observations that cerebral dysfunction can contribute to the
      pathogenesis of conversion disorder, and that nondominant hemisphere dysfunction
      may play a greater role.

PMID- 11514644
TI  - Comparison of extrapyramidal signs in dementia with Lewy bodies and Parkinson's
      disease.
AB  - Extrapyramidal signs (EPS) were compared in 98 dementia with Lewy bodies (DLB)
      and 130 medication-responsive Parkinson's disease (PD) patients. DLB patients
      were older at assessment and at disease onset, were cognitively more impaired,
      and had a shorter duration of disease than PD patients. Sixty-seven DLB patients
      (68%) showed EPS. The 58 DLB patients with complete data had more severe action
      tremor, body bradykinesia, difficulty arising from a chair, and facial
      expression, gait, and rigidity symptoms than PD patients (all P<0.001). Abnormal
      posture and tremor at rest did not differ. Severity of EPS correlated with age,
      duration of disease, and cognitive impairment in PD patients but not in DLB
      patients. Studies of the clinical significance and management of EPS in DLB
      patients are needed.

PMID- 11514645
TI  - Psychogenic hemifacial spasm.
AB  - Facial spasms that distort facial expression are typically due to facial
      dystonia, tics, and hemifacial spasm (HFS). Psychogenic facial spasms, however,
      have not been well characterized. The authors sought to 1) determine prevalence
      of psychogenic facial spasm in patients referred for evaluation of HFS and 2)
      draw attention to clinical characteristics and potential diagnostic pitfalls.
      Among 210 consecutive patients referred for evaluation of HFS, 5 (2.4%) received
      diagnoses of psychogenic facial spasm. All patients were female; mean age was
      34.6 years (range 26-45) and mean symptom duration 1.1 years (range 2 wk-2 yr).
      Onset was left-sided in 3 patients, and the lid was the initial site affected in
      2 patients. This series of patients shows that facial spasms, although usually of
      neurovascular etiology, may be the initial or only manifestation of a psychogenic
      movement disorder, often associated with an underlying depression.

PMID- 11514646
TI  - Impairments of attention and effort among patients with major affective
      disorders.
AB  - Impairments of attention are common among people with major affective disorders,
      yet the influence of effortful task demands on attentional performance in
      unipolar and bipolar illness has been little studied. The authors compared
      psychiatric inpatients with primary diagnoses of unipolar or bipolar affective
      disorder (n=27) and age-matched normal control subjects (n=20) on a battery of
      eight neuropsychological tasks designed to measure different attentional
      functions. There were low-effort and high-effort versions of each task.
      Significant group differences were consistently observed on tasks demanding
      sustained and focused attention, but not on tasks requiring visual selective
      attention. Although affective disorder patients showed impairments on most tasks
      regardless of level of task effort, group differences were greatest on high
      effort conditions. Results indicate that patients with major affective disorders
      show significant attentional impairments on most measures of effortful attention,
      and the magnitude of these impairments increases as the effortful demands of the
      task increase.

PMID- 11514647
TI  - Neuroactive steroid levels in patients with generalized anxiety disorder.
AB  - Serum levels of allopregnanolone, pregnenolone sulfate, and
      dehydroepiandrosterone sulfate were measured in 8 male patients with generalized
      anxiety disorder (GAD) and 8 healthy control subjects. Results suggest that
      patients with GAD have significantly lower levels of pregnenolone sulfate than
      control subjects.

PMID- 11514648
TI  - Relationship of gender and age at onset of schizophrenia to severity of
      dyskinesia.
AB  - The authors examined severity of dyskinesia in 119 men and 44 women, comparing by
      gender those with late-onset schizophrenia (LOS) versus early-onset schizophrenia
      (EOS). Women with LOS and men with EOS had more severe dyskinesia than men with
      LOS and women with EOS. Many factors, including the length of neuroleptic
      treatment, alcohol and smoking history, and menopausal status, may contribute to
      the severity of dyskinesia in older patients with schizophrenia.

PMID- 11514649
TI  - Cultural invariance and the diagnosis of delusions: information processing as a
      neurobiologically preferable criterion.

PMID- 11514651
TI  - Commentary: knowing and valuing.

PMID- 11514652
TI  - Commentary: a culturally invariant neuropsychiatry?

PMID- 11514655
TI  - Environmentally dependent delusions in dementia.

PMID- 11514656
TI  - Gabapentin-associated aggression.

PMID- 11514657
TI  - A subtype of auditory verbal hallucinations responds to fluvoxamine.

PMID- 11514658
TI  - Metoclopramide-related pisa syndrome in clozapine treatment.

PMID- 11514659
TI  - Dysproccia: a necessary new term for impaired higher brain processing.

PMID- 11514660
TI  - Canary Capgras.

PMID- 11514661
TI  - A structural basis for processivity.
AB  - The structures of a number of processive enzymes have been determined recently.
      These proteins remain attached to their polymeric substrates and may perform
      thousands of rounds of catalysis before dissociating. Based on the degree of
      enclosure of the substrate, the structures fall into two broad categories. In one
      group, the substrate is partially enclosed, while in the other class, enclosure
      is complete. In the latter case, enclosure is achieved by way of an asymmetric
      structure for some enzymes while others use a symmetrical toroid. In those cases
      where the protein completely encloses its polymeric substrate, the two are
      topologically linked and an immediate explanation for processivity is provided.
      In cases where there is only partial enclosure, the structural basis for
      processivity is less obvious. There are, for example, pairs of proteins that have
      quite similar structures but differ substantially in their processivity. It does
      appear, however, that the enzymes that are processive tend to be those that more
      completely enclose their substrates. In general terms, proteins that do not use
      topological restraint appear to achieve processivity by using a large interaction
      surface. This allows the enzyme to bind with moderate affinity at a multitude of
      adjacent sites distributed along its polymeric substrate. At the same time, the
      use of a large interaction surface minimizes the possibility that the enzyme
      might bind at a small number of sites with much higher affinity, which would
      interfere with sliding. Proteins that can both slide along a polymeric substrate,
      and, as well, recognize highly specific sites (e.g., some site-specific DNA
      binding proteins) appear to undergo a conformational change between the cognate
      and noncognate-binding modes.

PMID- 11514662
TI  - Sequence-structure analysis of FAD-containing proteins.
AB  - We have analyzed structure-sequence relationships in 32 families of flavin
      adenine dinucleotide (FAD)-binding proteins, to prepare for genomic-scale
      analyses of this family. Four different FAD-family folds were identified, each
      containing at least two or more protein families. Three of these families,
      exemplified by glutathione reductase (GR), ferredoxin reductase (FR), and p
      cresol methylhydroxylase (PCMH) were previously defined, and a family represented
      by pyruvate oxidase (PO) is newly defined. For each of the families, several
      conserved sequence motifs have been characterized. Several newly recognized
      sequence motifs are reported here for the PO, GR, and PCMH families. Each FAD
      fold can be uniquely identified by the presence of distinctive conserved sequence
      motifs. We also analyzed cofactor properties, some of which are conserved within
      a family fold while others display variability. Among the conserved properties is
      cofactor directionality: in some FAD-structural families, the adenine ring of the
      FAD points toward the FAD-binding domain, whereas in others the isoalloxazine
      ring points toward this domain. In contrast, the FAD conformation and orientation
      are conserved in some families while in others it displays some variability.
      Nevertheless, there are clear correlations among the FAD-family fold, the shape
      of the pocket, and the FAD conformation. Our general findings are as follows: (a)
      no single protein 'pharmacophore' exists for binding FAD; (b) in every FAD
      binding family, the pyrophosphate moiety binds to the most strongly conserved
      sequence motif, suggesting that pyrophosphate binding is a significant component
      of molecular recognition; and (c) sequence motifs can identify proteins that bind
      phosphate-containing ligands.

PMID- 11514663
TI  - Role of the single cysteine residue, Cys 3, of human and bovine cystatin B
      (stefin B) in the inhibition of cysteine proteinases.
AB  - Cystatin B is unique among cysteine proteinase inhibitors of the cystatin
      superfamily in having a free Cys in the N-terminal segment of the proteinase
      binding region. The importance of this residue for inhibition of target
      proteinases was assessed by studies of the affinity and kinetics of interaction
      of human and bovine wild-type cystatin B and the Cys 3-to-Ser mutants of the
      inhibitors with papain and cathepsins L, H, and B. The wild-type forms from the
      two species had about the same affinity for each proteinase, binding tightly to
      papain and cathepsin L and more weakly to cathepsins H and B. In general, these
      affinities were appreciably higher than those reported earlier, perhaps because
      of irreversible oxidation of Cys 3 in previous work. The Cys-to-Ser mutation
      resulted in weaker binding of cystatin B to all four proteinases examined, the
      effect varying with both the proteinase and the species variant of the inhibitor.
      The affinities of the human inhibitor for papain and cathepsin H were decreased
      by threefold to fourfold and that for cathepsin B by approximately 20-fold,
      whereas the reductions in the affinities of the bovine inhibitor for papain and
      cathepsins H and B were approximately 14-fold, approximately 10-fold and
      approximately 300-fold, respectively. The decreases in affinity for cathepsin L
      could not be properly quantified but were greater than threefold. Increased
      dissociation rate constants were responsible for the weaker binding of both
      mutants to papain. By contrast, the reduced affinities for cathepsins H and B
      were due to decreased association rate constants. Cys 3 of both human and bovine
      cystatin B is thus of appreciable importance for inhibition of cysteine
      proteinases, in particular cathepsin B.

PMID- 11514664
TI  - Oligomerization and ligand binding in a homotetrameric hemoglobin: two high
      resolution crystal structures of hemoglobin Bart's (gamma(4)), a marker for alpha
      thalassemia.
AB  - Hemoglobin (Hb) Bart's is present in the red blood cells of millions of people
      worldwide who suffer from alpha-thalassemia. alpha-Thalassemia is a disease in
      which there is a deletion of one or more of the four alpha-chain genes, and
      excess gamma and beta chains spontaneously form homotetramers. The gamma(4)
      homotetrameric protein known as Hb Bart's is a stable species that exhibits
      neither a Bohr effect nor heme-heme cooperativity. Although Hb Bart's has a
      higher O(2) affinity than either adult (alpha(2)beta(2)) or fetal
      (alpha(2)gamma(2)) Hbs, it has a lower affinity for O(2) than HbH (beta(4)). To
      better understand the association and ligand binding properties of the gamma(4)
      tetramer, we have solved the structure of Hb Bart's in two different oxidation
      and ligation states. The crystal structure of ferrous carbonmonoxy (CO) Hb Bart's
      was determined by molecular replacement and refined at 1.7 A resolution (R =
      21.1%, R(free) = 24.4%), and that of ferric azide (N(3)(-)) Hb Bart's was
      similarly determined at 1.86 A resolution (R = 18.4%, R(free) = 22.0%). In the
      carbonmonoxy-Hb structure, the CO ligand is bound at an angle of 140 degrees, and
      with an unusually long Fe-C bond of 2.25 A. This geometry is attributed to
      repulsion from the distal His63 at the low pH of crystallization (4.5). In
      contrast, azide is bound to the oxidized heme iron in the methemoglobin crystals
      at an angle of 112 degrees, in a perfect orientation to accept a hydrogen bond
      from His63. Compared to the three known quaternary structures of human Hb (T, R,
      and R2), both structures most closely resemble the R state. Comparisons with the
      structures of adult Hb and HbH explain the association and dissociation behaviour
      of Hb homotetramers relative to the heterotetrameric Hbs.

PMID- 11514665
TI  - Mechanism of pressure-induced thermostabilization of proteins: studies of
      glutamate dehydrogenases from the hyperthermophile Thermococcus litoralis.
AB  - In this study, we investigated the effect of pressure on protein structure and
      stability at high temperature. Thermoinactivation experiments at 5 and 500 atm
      were performed using the wild-type (WT) enzyme and two single mutants (D167T and
      T138E) of the glutamate dehydrogenase (GDH) from the hyperthermophile
      Thermococcus litoralis. All three GDHs were stabilized, although to different
      degrees, by the application of 500 atm. Interestingly, the degree of pressure
      stabilization correlated with GDH stability as well as the magnitude of
      electrostatic repulsion created by residues at positions 138 and 167.
      Thermoinactivation experiments also were performed in the presence of trehalose.
      Addition of the sugar stabilized all three GDHs; the degree of sugar-induced
      thermostabilization followed the same order as pressure stabilization. Previous
      studies suggested a mechanism whereby the enzyme adopts a more compact and rigid
      structure and volume fluctuations away from the native state are diminished under
      pressure. The present results on the three GDHs allowed us to further confirm and
      refine the proposed mechanism for pressure-induced thermostabilization. In
      particular, we propose that pressure stabilizes against thermoinactivation by
      shifting the equilibrium between conformational substates of the GDH hexamer,
      thus inhibiting irreversible aggregation.

PMID- 11514667
TI  - Rational design of enantioselective enzymes requires considerations of entropy.
AB  - Entropy was shown to play an equally important role as enthalpy for how
      enantioselectivity changes when redesigning an enzyme. By studying the
      temperature dependence of the enantiomeric ratio E of an enantioselective enzyme,
      its differential activation enthalpy (Delta(R-S)DeltaH(++)) and entropy (Delta(R
      S)DeltaS(++)) components can be determined. This was done for the resolution of 3
      methyl-2-butanol catalyzed by Candida antarctica lipase B and five variants with
      one or two point mutations. Delta(R-S)DeltaS(++) was in all cases equally
      significant as Delta(R-S)DeltaH(++) to E. One variant, T103G, displayed an
      increase in E, the others a decrease. The altered enantioselectivities of the
      variants were all related to simultaneous changes in Delta(R-S)DeltaH(++) and
      Delta(R-S)DeltaS(++). Although the changes in Delta(R-S)DeltaH(++) and Delta(R
      S)DeltaS(++) were of a compensatory nature the compensation was not perfect,
      thereby allowing modifications of E. Both the W104H and the T103G variants
      displayed larger Delta(R-S)DeltaH(++) than wild type but exhibited a decrease or
      increase, respectively, in E due to their different relative increase in Delta(R
      S)DeltaS(++).

PMID- 11514666
TI  - Phenylalanine fluorescence studies of calcium binding to N-domain fragments of
      Paramecium calmodulin mutants show increased calcium affinity correlates with
      increased disorder.
AB  - Calmodulin (CaM) is a ubiquitous, essential calcium-binding protein that
      regulates diverse protein targets in response to physiological calcium
      fluctuations. Most high-resolution structures of CaM-target complexes indicate
      that the two homologous domains of CaM are equivalent partners in target
      recognition. However, mutations between calcium-binding sites I and II in the N
      domain of Paramecium calmodulin (PCaM) selectively affect calcium-dependent
      sodium currents. To understand these domain-specific effects, N-domain fragments
      (PCaM(1-75)) of six of these mutants were examined to determine whether
      energetics of calcium binding to sites I and II or conformational properties had
      been perturbed. These PCaM((1-75)) sequences naturally contain 5 Phe residues but
      no Tyr or Trp; calcium binding was monitored by observing the reduction in
      intrinsic phenylalanine fluorescence at 280 nm. To assess mutation-induced
      conformational changes, thermal denaturation of the apo PCaM((1-75)) sequences,
      and calcium-dependent changes in Stokes radii were determined. The free energy of
      calcium binding to each mutant was within 1 kcal/mole of the value for wild type
      and calcium reduced the R(s) of all of them. A striking trend was observed
      whereby mutants showing an increase in calcium affinity and R(s) had a
      concomitant decrease in thermal stability (by as much as 18 degrees C). Thus,
      mutations between the binding sites that increased disorder and reduced tertiary
      constraints in the apo state promoted calcium coordination. This finding
      underscores the complexity of the linkage between calcium binding and
      conformational change and the difficulty in predicting mutational effects.

PMID- 11514668
TI  - Role of the single disulphide bond of beta(2)-microglobulin in amyloidosis in
      vitro.
AB  - The aggregation of beta(2)-microglobulin (beta(2)m) into amyloid fibrils occurs
      in the condition known as dialysis-related amyloidosis (DRA). The protein has a
      beta-sandwich fold typical of the immunoglobulin family, which is stabilized by a
      highly conserved disulphide bond linking Cys25 and Cys80. Oxidized beta(2)m forms
      amyloid fibrils rapidly in vitro at acidic pH and high ionic strength. Here we
      investigate the role of the single disulphide bond of beta(2)m in amyloidosis in
      vitro. We show that reduction of the disulphide bond destabilizes the native
      protein such that non-native molecules are populated at neutral pH. These species
      are prone to oligomerization but do not form amyloid fibrils when incubated for
      up to 8 mo at pH 7.0 in 0.4 M NaCl. Over the pH range 4.0-1.5 in the presence of
      0.4 M NaCl, however, amyloid fibrils of reduced beta(2)m are formed. These
      fibrils are approximately 10 nm wide, but are shorter and assemble more rapidly
      than those produced from the oxidized protein. These data show that population of
      non-native conformers of beta(2)m at neutral pH by reduction of its single
      disulphide bond is not sufficient for amyloid formation. Instead, association of
      one or more specific partially unfolded molecules formed at acid pH are necessary
      for the formation of beta(2)m amyloid in vitro. Further experiments will now be
      needed to determine the role of different oligomeric species of beta(2)m in the
      toxicity of the protein in vivo.

PMID- 11514669
TI  - Substitution of conserved methionines by leucines in chloroplast small heat shock
      protein results in loss of redox-response but retained chaperone-like activity.
AB  - During evolution of land plants, a specific motif occurred in the N-terminal
      domain of the chloroplast-localized small heat shock protein, Hsp21: a sequence
      with highly conserved methionines, which is predicted to form an amphipathic
      alpha-helix with the methionines situated along one side. The functional role of
      these conserved methionines is not understood. We have found previously that
      treatment, which causes methionine sulfoxidation in Hsp21, also leads to
      structural changes and loss of chaperone-like activity. Here, mutants of
      Arabidopsis thaliana Hsp21 protein were created by site-directed mutagenesis,
      whereby conserved methionines were substituted by oxidation-resistant leucines.
      Mutants lacking the only cysteine in Hsp21 were also created. Protein analyses by
      nondenaturing electrophoresis, size exclusion chromatography, and circular
      dichroism proved that sulfoxidation of the four highly conserved methionines
      (M49, M52, M55, and M59) is responsible for the oxidation-induced conformational
      changes in the Hsp21 oligomer. In contrast, the chaperone-like activity was not
      ultimately dependent on the methionines, because it was retained after methionine
      to-leucine substitution. The functional role of the conserved methionines in
      Hsp21 may be to offer a possibility for redox control of chaperone-like activity
      and oligomeric structure dynamics.

PMID- 11514670
TI  - Effects of turn residues in directing the formation of the beta-sheet and in the
      stability of the beta-sheet.
AB  - The designed peptide (denoted 20-mer, sequence VFITS(D)PGKTYTEV(D)PGOKILQ) has
      been shown to form a three-strand antiparallel beta-sheet. It is generally
      believed that the (D)Pro-Gly segment has the propensity to adopt a type II' beta
      turn, thereby promoting the formation of this beta-sheet. Here, we replaced
      (D)Pro-Gly with Asp-Gly, which should favor a type I' turn, to examine the
      influence of different type of turns on the stability of the beta-sheet. Contrary
      to our expectation, the mutant peptide, denoted P6D, forms a five-residue type I
      turn plus a beta-bulge between the first two strands due to a one amino-acid
      frameshift in the hydrogen bonding network and side-chain inversion of the first
      beta-strand. In contrast, the same kind of substitution at (D)Pro-14 in the
      double mutant, denoted P6DP14D, does not yield the same effect. These
      observations suggest that the SDGK sequence disfavors the type I' conformation
      while the VDGO sequence favors a type I' turn, and that the frameshift in the
      first strand provides a way for the peptide to accommodate a disfavored turn
      sequence by protruding a bulge in the formation of the beta-hairpin. Thus,
      different types of turns can affect the stability of a beta-structure.

PMID- 11514671
TI  - The sequence determinants of cadherin molecules.
AB  - The sequence and structural analysis of cadherins allow us to find sequence
      determinants-a few positions in sequences whose residues are characteristic and
      specific for the structures of a given family. Comparison of the five
      extracellular domains of classic cadherins showed that they share the same
      sequence determinants despite only a nonsignificant sequence similarity between
      the N-terminal domain and other extracellular domains. This allowed us to predict
      secondary structures and propose three-dimensional structures for these domains
      that have not been structurally analyzed previously. A new method of assigning a
      sequence to its proper protein family is suggested: analysis of sequence
      determinants. The main advantage of this method is that it is not necessary to
      know all or almost all residues in a sequence as required for other traditional
      classification tools such as BLAST, FASTA, and HMM. Using the key positions only,
      that is, residues that serve as the sequence determinants, we found that all
      members of the classic cadherin family were unequivocally selected from among
      80,000 examined proteins. In addition, we proposed a model for the secondary
      structure of the cytoplasmic domain of cadherins based on the principal relations
      between sequences and secondary structure multialignments. The patterns of the
      secondary structure of this domain can serve as the distinguishing
      characteristics of cadherins.

PMID- 11514672
TI  - Arginine-140 and isoleucine-141 determine the 17beta-estradiol-binding
      specificity of the sex-steroid-binding protein (SBP, or SHBG) of human plasma.
AB  - Arginine-140 and isoleucine-141 were identified as key determinants of 17beta
      estradiol (E(2)) binding affinity of the sex-steroid-binding protein (SBP, or
      SHBG) of human plasma. Amino acid residues that differ between human and rabbit
      SBP sequences were replaced in the human protein and the products tested for
      lowered E(2)binding activity as are seen in the rabbit protein. Only mutants
      containing either R140K or I141L replacements display an E(2) equilibrium
      dissociation constant (Kd) higher than the wild type, reaching a value of 30 nM
      when both were present. The 5alpha-dihydrotestosterone (DHT) equilibrium
      dissociation constant of these mutants was unaffected. The quadruple mutant
      M107I/I138V/R140K/I141L yielded an E(2) Kd of 65 nM, significantly closer to the
      80 nM rabbit SBP E(2) Kd value. Although mutants containing the M107I and I138V
      replacements in the absence of R140K and I141L had normal E(2) Kds, the presence
      of the M107I replacement in the quadruple mutant was necessary to obtain an
      accurate E(2) Kd value by competitive Scatchard analysis. Molecular modeling
      using coordinates for the recently determined N-terminal domain of human SBP
      revealed a significant shift of the F56 phenyl ring away from ring A of E(2) in
      mutant models containing the R140K and I141L replacements. We conclude that R140
      and I141 are required for sustaining the right proximity of the phenyl ring of
      F56 to ring A of 17beta-estradiol, thus optimizing the E(2)-binding affinity of
      human SBP.

PMID- 11514673
TI  - Influence of Glu-376 --> Gln mutation on enthalpy and heat capacity changes for
      the binding of slightly altered ligands to medium chain acyl-CoA dehydrogenase.
AB  - We showed that the alpha-CH(2) --> NH substitution in octanoyl-CoA alters the
      ground and transition state energies for the binding of the CoA ligands to medium
      chain acyl-CoA dehydrogenase (MCAD), and such an effect is caused by a small
      electrostatic difference between the ligands. To ascertain the extent that the
      electrostatic contribution of the ligand structure and/or the enzyme site
      environment modulates the thermodynamics of the enzyme-ligand interaction, we
      undertook comparative microcalorimetric studies for the binding of 2-azaoctanoyl
      CoA (alpha-CH(2) --> NH substituted octanoyl-CoA) and octenoyl-CoA to the wild
      type and Glu-376 --> Gln mutant enzymes. The experimental data revealed that both
      enthalpy (DeltaH degrees ) and heat capacity changes (DeltaC(p) degrees ) for the
      binding of 2-azaoctanoyl-CoA (DeltaH degrees (298) = -21.7 +/- 0.8 kcal/mole,
      DeltaC(p) degrees = -0.627 +/- 0.04 kcal/mole/K) to the wild-type MCAD were more
      negative than those obtained for the binding of octenoyl-CoA (DeltaH degrees
      (298) = -17.2 +/- 1.6 kcal/mole, DeltaC(p) degrees = -0.526 +/- 0.03
      kcal/mole/K). Of these, the decrease in the magnitude of DeltaC(p) degrees for
      the binding of 2-azaoctanoyl-CoA (vis-a-vis octenoyl-CoA) to the enzyme was
      unexpected, because the former ligand could be envisaged to be more polar than
      the latter. To our further surprise, the ligand-dependent discrimination in the
      above parameters was completely abolished on Glu-376 --> Gln mutation of the
      enzyme. Both DeltaH degrees and DeltaC(p) degrees values for the binding of 2
      azaoctanoyl-CoA (DeltaH degrees (298) = -13.3 +/- 0.6 kcal/mole, DeltaC(p)
      degrees = -0.511 +/- 0.03 kcal/mole/K) to the E376Q mutant enzyme were found to
      be correspondingly identical to those obtained for the binding of octenoyl-CoA
      (DeltaH degrees (298) = -13.2 +/- 0.6 kcal/mole, DeltaC(p) degrees = -0.520 +/-
      0.02 kcal/mole/K). However, in neither case could the experimentally determined
      DeltaC(p) degrees values be predicted on the basis of the changes in the water
      accessible surface areas of the enzyme and ligand species. Arguments are
      presented that the origin of the above thermodynamic differences lies in solvent
      reorganization and water-mediated electrostatic interaction between ligands and
      enzyme site groups, and such interactions are intrinsic to the molecular basis of
      the enzyme-ligand complementarity.

PMID- 11514674
TI  - A cofactor-dependent phosphoglycerate mutase homolog from Bacillus
      stearothermophilus is actually a broad specificity phosphatase.
AB  - The distribution of phosphoglycerate mutase (PGM) activity in bacteria is
      complex, with some organisms possessing both a cofactor-dependent and a cofactor
      independent PGM and others having only one of these enzymes. Although Bacillus
      species contain only a cofactor-independent PGM, genes homologous to those
      encoding cofactor-dependent PGMs have been detected in this group of bacteria,
      but in at least one case the encoded protein lacks significant PGM activity. Here
      we apply sequence analysis, molecular modeling, and enzymatic assays to the
      cofactor-dependent PGM homologs from B. stearothermophilus and B. subtilis, and
      show that these enzymes are phosphatases with broad substrate specificity.
      Homologs from other gram-positive bacteria are also likely to possess phosphatase
      activity. These studies clearly show that the exploration of genomic sequences
      through three-dimensional modeling is capable of producing useful predictions
      regarding function. However, significant methodological improvements will be
      needed before such analysis can be carried out automatically.

PMID- 11514675
TI  - Site-directed mutations of human hemoglobin at residue 35beta: a residue at the
      intersection of the alpha1beta1, alpha1beta2, and alpha1alpha2 interfaces.
AB  - Because Tyr35beta is located at the convergence of the alpha1beta1, alpha1beta2,
      and alpha1alpha2 interfaces in deoxyhemoglobin, it can be argued that mutations
      at this position may result in large changes in the functional properties of
      hemoglobin. However, only small mutation-induced changes in functional and
      structural properties are found for the recombinant hemoglobins betaY35F and
      betaY35A. Oxygen equilibrium-binding studies in solution, which measure the
      overall oxygen affinity (the p50) and the overall cooperativity (the Hill
      coefficient) of a hemoglobin solution, show that removing the phenolic hydroxyl
      group of Tyr35beta results in small decreases in oxygen affinity and
      cooperativity. In contrast, removing the entire phenolic ring results in a
      fourfold increase in oxygen affinity and no significant change in cooperativity.
      The kinetics of carbon monoxide (CO) combination in solution and the oxygen
      binding properties of these variants in deoxy crystals, which measure the oxygen
      affinity and cooperativity of just the T quaternary structure, show that the
      ligand affinity of the T quaternary structure decreases in betaY35F and increases
      in betaY35A. The kinetics of CO rebinding following flash photolysis, which
      provides a measure of the dissociation of the liganded hemoglobin tetramer,
      indicates that the stability of the liganded hemoglobin tetramer is not altered
      in betaY35F or betaY35A. X-ray crystal structures of deoxy betaY35F and betaY35A
      are highly isomorphous with the structure of wild-type deoxyhemoglobin. The
      betaY35F mutation repositions the carboxyl group of Asp126alpha1 so that it may
      form a more favorable interaction with the guanidinium group of Arg141alpha2. The
      betaY35A mutation results in increased mobility of the Arg141alpha side chain,
      implying that the interactions between Asp126alpha1 and Arg141alpha2 are
      weakened. Therefore, the changes in the functional properties of these 35beta
      mutants appear to correlate with subtle structural differences at the C terminus
      of the alpha-subunit.

PMID- 11514676
TI  - NMR of hydrogen bonding in cold-shock protein A and an analysis of the influence
      of crystallographic resolution on comparisons of hydrogen bond lengths.
AB  - Hydrogen bonding in cold-shock protein A of Escherichia coli has been
      investigated using long-range HNCO spectroscopy. Nearly half of the amide protons
      involved in hydrogen bonds in solution show no measurable protection from
      exchange in water, cautioning against a direct correspondence between hydrogen
      bonding and hydrogen exchange protection. The N to O atom distance across a
      hydrogen bond, R(NO), is related to the size of the (3h)J(NC') trans hydrogen
      bond coupling constant and the amide proton chemical shift. Both NMR parameters
      show poorer agreement with the 2.0-A resolution X-ray structure of the cold-shock
      protein studied by NMR than with a 1.2-A resolution X-ray structure of a
      homologous cold-shock protein from the thermophile B. caldolyticus. The influence
      of crystallographic resolution on comparisons of hydrogen bond lengths was
      further investigated using a database of 33 X-ray structures of ribonuclease A.
      For highly similar structures, both hydrogen bond R(NO) distance and Calpha
      coordinate root mean square deviations (RMSD) show systematic increases as the
      resolution of the X-ray structure used for comparison decreases. As structures
      diverge, the effects of coordinate errors on R(NO) distance and Calpha coordinate
      root mean square deviations become progressively smaller. The results of this
      study are discussed with regard to the influence of data precision on
      establishing structure similarity relationships between proteins.

PMID- 11514677
TI  - Structures of an unliganded neurophysin and its vasopressin complex: implications
      for binding and allosteric mechanisms.
AB  - The structures of des 1-6 bovine neurophysin-II in the unliganded state and as
      its complex with lysine vasopressin were determined crystallographically at
      resolutions of 2.4 A and 2.3 A, respectively. The structure of the protein
      component of the vasopressin complex was, with some local differences, similar to
      that determined earlier of the full-length protein complexed with oxytocin, but
      relatively large differences, probably intrinsic to the hormones, were observed
      between the structures of bound oxytocin and bound vasopressin at Gln 4. The
      structure of the unliganded protein is the first structure of an unliganded
      neurophysin. Comparison with the liganded state indicated significant binding
      induced conformational changes that were the largest in the loop region
      comprising residues 50-58 and in the 7-10 region. A subtle binding-induced
      tightening of the subunit interface of the dimer also was shown, consistent with
      a role for interface changes in neurophysin allosteric mechanism, but one that is
      probably not predominant. Interface changes are suggested to be communicated from
      the binding site through the strands of beta-sheet that connect these two
      regions, in part with mediation by Gly 23. Comparison of unliganded and liganded
      states additionally reveals that the binding site for the hormone alpha-amino
      group is largely preformed and accessible in the unliganded state, suggesting
      that it represents the initial site of hormone protein recognition. The potential
      molecular basis for its thermodynamic contribution to binding is discussed.

PMID- 11514678
TI  - Circularly permuted proteins in the protein structure database.
AB  - Some proteins are homologous to others after their sequence is circularly
      permuted. A few such proteins have been recognized, mainly by sequence
      comparison, but also by comparing their three-dimensional structures. Here we
      report the result of a systematic search for all protein pairs in the SCOP 90% id
      domain database that become structurally superimposable when the sequence of one
      of the pairs is circularly permuted. Using a reasonable set of criteria, we find
      that 47% of all protein domains are superimposable to at least one other protein
      domain in the database after their sequence is circularly permuted. Many of these
      are symmetric proteins, which superimpose to another protein both with and
      without a circular permutation of the sequence. However, 412 of the total 3035
      domains are nonsymmetric, and these become structurally superimposable to another
      protein only after a circular permutation of the sequence. These include most
      known and many previously undetected circularly permuted proteins with remote
      homology.

PMID- 11514679
TI  - Chemical denaturation and elevated folding temperatures are required for wild
      type activity and stability of recombinant Methanococcus jannaschii 20S
      proteasome.
AB  - The 20S proteasome from the extreme thermophile Methanococcus jannaschii (Mj) was
      purified and sequenced to facilitate production of the recombinant proteasome in
      E. coli. The recombinant proteasome remained in solution at a purity level of 80
      85% (according to SDS PAGE) following incubation of cell lysates at 70 degrees C.
      Temperature-activity profiles indicated that the temperature optima of the wild
      type and recombinant enzymes differed substantially, with optimal activities
      occurring at 119 degrees C and 95 degrees C, respectively. To ameliorate this
      discrepancy, two recombinant enzyme preparations were produced, each of which
      included denaturation of the proteasome by 4 M urea followed by high-temperature
      (85 degrees C) dialysis. The wild-type temperature optimum was restored, but only
      if proteasome subunits were denatured and refolded prior to assembly (a
      preparation designated as alpha & beta). In contrast, when proteasome assembly
      preceded denaturation (designated alpha + beta) the optimum temperature was
      raised to a lesser degree. Moreover, the alpha & beta and alpha + beta
      preparations had apparent thermal half-lives at 114 degrees C of 54.2 and 26.2
      min, respectively, and the thermostability of the less stable enzyme was more
      sensitive to a reduction in pH. Attainment of wild-type activity and stability
      thus required the proper folding of both the alpha- and beta-subunits prior to
      proteasome assembly. Consistent with this behavior, dual-scanning calorimetry
      (DSC) measurements revealed differences in the reassembly efficiency of the two
      proteasome preparations. The ability to produce structural conformers with
      dramatically different thermal optima and thermostabilities may facilitate the
      determination of molecular forces and structural motifs responsible for enzyme
      thermostablity and high-temperature activity.

PMID- 11514680
TI  - Characterization of bothrojaracin interaction with human prothrombin.
AB  - Bothrojaracin (BJC) is a 27-kD snake venom protein from Bothrops jararaca that
      has been characterized as a potent thrombin inhibitor. BJC binds to exosites I
      and II, with a dissociation constant of 0.7 nM, and influences but does not block
      the proteinase catalytic site. BJC also binds prothrombin through an interaction
      that has not been characterized. In the present work we characterize the
      interaction of BJC with prothrombin quantitatively for the first time, and
      identify the BJC binding site on human prothrombin. Gel filtration chromatography
      demonstrated calcium-independent, 1:1 complex formation between fluorescein
      labeled BJC ([5F]BJC) and prothrombin, whereas no interactions were observed with
      activation fragments 1 or 2 of prothrombin. Isothermal titration calorimetry
      showed that binding of BJC to prothrombin is endothermic, with a dissociation
      constant of 76 +/- 32 nM. The exosite I-specific ligand, hirudin(54-65) (Hir(54
      65) (SO(3)(-)), displaced competitively [5F]BJC from prothrombin. Titration of
      the fluorescent hirudin(54-65) derivative, [5F]Hir(54-65)(SO(3)(-)), with human
      prothrombin showed a dissociation constant of 7.0 +/- 0.2 microM, indicating a
      approximately 100-fold lower binding affinity than that exhibited by BJC. Both
      ligands, however, displayed a similar, approximately 100-fold increase in
      affinity for exosite I when prothrombin was activated to thrombin. BJC
      efficiently displaced [5F]Hir(54-65)(SO(3)(-)) from complexes formed with
      thrombin or prothrombin with dissociation constants of 0.7 +/- 0.9 nM and 11 +/-
      80 nM, respectively, indicating that BJC and Hir(54-65)(SO(3)(-)) compete for the
      same exosite on these molecules. The results indicate that BJC is a potent and
      specific probe of the partially exposed anion-binding exosite (proexosite I) of
      human prothrombin.

PMID- 11514681
TI  - N-terminal extension changes the folding mechanism of the FK506-binding protein.
AB  - Many of the protein fusion systems used to enhance the yield of recombinant
      proteins result in the addition of a small number of amino acid residues onto the
      desired protein. Here, we investigate the effect of short (three amino acid) N
      terminal extensions on the equilibrium denaturation and kinetic folding and
      unfolding reactions of the FK506-binding protein (FKBP) and compare the results
      obtained with data collected on an FKBP variant lacking this extension.
      Isothermal equilibrium denaturation experiments demonstrated that the N-terminal
      extension had a slight destabilizing effect. NMR investigations showed that the N
      terminal extension slightly perturbed the protein structure near the site of the
      extension, with lesser effects being propagated into the single alpha-helix of
      FKBP. These structural perturbations probably account for the differential
      stability. In contrast to the relatively minor equilibrium effects, the N
      terminal extension generated a kinetic-folding intermediate that is not observed
      in the shorter construct. Kinetic experiments performed on a construct with a
      different amino acid sequence in the extension showed that the length and the
      sequence of the extension both contribute to the observed equilibrium and kinetic
      effects. These results point to an important role for the N terminus in the
      folding of FKBP and suggest that a biological consequence of N-terminal
      methionine removal observed in many eukaryotic and prokaryotic proteins is to
      increase the folding efficiency of the polypeptide chain.

PMID- 11514682
TI  - The PYRIN domain: a member of the death domain-fold superfamily.
AB  - PYRIN domains were identified recently as putative protein-protein interaction
      domains at the N-termini of several proteins thought to function in apoptotic and
      inflammatory signaling pathways. The approximately 95 residue PYRIN domains have
      no statistically significant sequence homology to proteins with known three
      dimensional structure. Using secondary structure prediction and potential-based
      fold recognition methods, however, the PYRIN domain is predicted to be a member
      of the six-helix bundle death domain-fold superfamily that includes death domains
      (DDs), death effector domains (DEDs), and caspase recruitment domains (CARDs).
      Members of the death domain-fold superfamily are well established mediators of
      protein-protein interactions found in many proteins involved in apoptosis and
      inflammation, indicating further that the PYRIN domains serve a similar function.
      An homology model of the PYRIN domain of CARD7/DEFCAP/NAC/NALP1, a member of the
      Apaf-1/Ced-4 family of proteins, was constructed using the three-dimensional
      structures of the FADD and p75 neurotrophin receptor DDs, and of the Apaf-1 and
      caspase-9 CARDs, as templates. Validation of the model using a variety of
      computational techniques indicates that the fold prediction is consistent with
      the sequence. Comparison of a circular dichroism spectrum of the PYRIN domain of
      CARD7/DEFCAP/NAC/NALP1 with spectra of several proteins known to adopt the death
      domain-fold provides experimental support for the structure prediction.

PMID- 11514683
TI  - Antibodies against Pseudomonas aeruginosa in patients with bronchiectasis:
      helpful or harmful?

PMID- 11514685
TI  - Anti-Pseudomonas aeruginosa antibody detection in patients with bronchiectasis
      without cystic fibrosis.
AB  - BACKGROUND: Pseudomonas aeruginosa is a frequent cause of infection in patients
      with bronchiectasis. Differentiation between non-infected patients and those with
      different degrees of P aeruginosa infection could influence the management and
      prognosis of these patients. The diagnostic usefulness of serum IgG antibodies
      against P aeruginosa outer membrane proteins was determined in patients with
      bronchiectasis without cystic fibrosis. METHODS: Fifty six patients were
      classified according to sputum culture into three groups: group A (n=18) with no
      P aeruginosa in any sample; group B (n=18) with P aeruginosa alternating with
      other microorganisms; and group C (n=20) with P aeruginosa in all sputum samples.
      Each patient had at least three sputum cultures in the 6 months prior to serum
      collection. Detection of antibodies was performed by Western blot and their
      presence against 20 protein bands (10-121 kd) was assessed. RESULTS: Antibodies
      to more than four bands in total or to five individual bands (36, 26, 22, 20 or
      18 kd) differentiated group B from group A, while antibodies to a total of more
      than eight bands or to 10 individual bands (104, 69, 63, 56, 50, 44, 30, 25, 22,
      13 kd) differentiated group C from group B. When discordant results between the
      total number of bands and the frequency of P aeruginosa isolation were obtained,
      the follow up of patients suggested that the former, in most cases, predicted
      chronic P aeruginosa colonisation. CONCLUSION: In patients with bronchiectasis
      the degree of P aeruginosa infection can be determined by the number and type of
      outer membrane protein bands indicating which serum antibodies are present.

PMID- 11514686
TI  - Effects of inhaled salbutamol in exercising non-asthmatic athletes.
AB  - BACKGROUND: Beta-2 agonists such as salbutamol are used, not only by asthmatic
      athletes to prevent exercise induced asthma, but also by non-asthmatic athletes
      as a potentially ergogenic agent. We have investigated whether inhaled salbutamol
      enhances endurance performance in non-asthmatic athletes. METHODS: A prospective
      double blind, randomised, three way crossover design was used to study the
      effects of 200 microg and 800 microg inhaled salbutamol versus a placebo in 12
      trained triathletes. The treatments were compared in three identical cycle
      ergometer sessions at 85% of the predetermined maximal oxygen uptake. Lung
      function, endurance time, metabolic parameters (glucose, potassium, lactate, free
      fatty acid, and glycerol), and psychomotor performance were evaluated. RESULTS:
      Neither endurance time nor post-exercise bronchodilation were significantly
      different between the treatments. Metabolic parameters were affected by exercise
      but not by treatment. CONCLUSIONS: Inhaled salbutamol, even in a high dose, did
      not have a significant effect on endurance performance in non-asthmatic athletes,
      although the bronchodilating effect of the drug at the beginning of exercise may
      have improved respiratory adaptation. Our results do not preclude an ergogenic
      effect of beta2 agonists given by other routes or for a longer period.

PMID- 11514688
TI  - Changing patterns of hospital admission for asthma, 1981-97.
AB  - BACKGROUND: Hospital admission rates for asthma have stopped rising in several
      countries. The aim of this study was to use linked hospital admission data to
      explore recent trends in asthma admissions in Scotland. METHODS: Linked Scottish
      Morbidity Records (SMR1) for asthma (ICD-9 493 and ICD-10 J45-6) from 1981 to
      1997 were used to describe rates of first admissions and readmissions by age and
      sex. As a measure of resource use, annual trends in bed days used were also
      explored by age and sex. RESULTS: There were 160 039 hospital admissions for
      asthma by 82 421 individuals in Scotland during the study period. The overall
      hospital admission rate increased by 122% (from 106.7 to 236.7 per 100 000
      population) but this varied by sex, age, and admission type. First admissions
      rose by 70% from 73.2 per 100 000 in 1986 to 124.8 per 100 000 in 1997 while
      readmissions fell. Children (<15 years) experienced a decline in overall
      admissions after 1992 due to falls in both new admissions and readmissions. By
      1997 the ratio of female to male admissions was 0.57 in children, but 1.50 above
      14 years of age. Mean lengths of stay fell from 10.7 days to 3.7 days between
      1981 and 1997 and bed days used showed little change except for a decline after
      1992 in children. CONCLUSIONS: After a period of increasing hospitalisation for
      asthma in Scotland, rates of admission among children have begun to fall but
      among adults admissions continue to rise.

PMID- 11514687
TI  - Airway function at one year: association with premorbid airway function,
      wheezing, and maternal smoking.
AB  - BACKGROUND: Impaired growth and development of the respiratory system during
      fetal and early postnatal life may have important implications for lung
      development and later lung health. The aim of this study was to examine the
      association of diminished premorbid airway function, prior wheezing, and maternal
      smoking with airway function at 1 year of age. METHODS: Respiratory function was
      measured at the end of the first year in 100 of 108 healthy term infants (93%) in
      whom similar measurements had been undertaken prior to any respiratory illness at
      8 weeks. Physician diagnosed wheezing episodes were identified retrospectively
      from medical records. RESULTS: At 1 year specific airway conductance during end
      expiration (sGawEE; /s/kPa) was significantly diminished in those infants with
      prior wheezing (95% CI wheeze/no wheeze -0.76 to -0.14), mothers who smoked (95%
      CI smoke/no smoke -0.81 to -0.27), a family history of asthma (95% CI family
      history/no family history -0.62 to 0.00), or diminished premorbid sGawEE (95% CI 
      0.13 to -0.43/s/kPa per unit reduction sGawEE at 8 weeks). In a multivariate
      model only maternal smoking and diminished premorbid sGawEE were independently
      associated with diminished sGawEE at 1 year. CONCLUSIONS: Diminished airway
      function at the end of the first year appears to be mediated by impaired airway
      development during early life as well as by exposure to maternal smoking. These
      findings are consistent with the hypothesis that, at a population level,
      diminished premorbid airway function provides the link between wheezing lower
      respiratory illness and diminished airway function at 1 year. Maternal smoking
      remains an important and avoidable cause of impaired airway development and
      function in infancy.

PMID- 11514689
TI  - Reference values of interrupter respiratory resistance in healthy preschool white
      children.
AB  - BACKGROUND: Interrupter respiratory resistance (Rint) is reported to be useful in
      evaluating lung function in poorly collaborating patients. However, no reference
      values are available from large samples of preschool children using the standard
      interrupter method. The aim of this study was to define reference Rint values in
      a population of healthy preschool children. METHODS: Rint was assessed without
      supporting the cheeks in children with no history of wheeze from six
      kindergartens. To evaluate the effects of upper airway compliance on Rint in
      healthy children, an additional group of preschool children with either no
      history of wheeze or no respiratory symptoms at the time of testing underwent
      Rint measurements in our lung function laboratory with and without supporting the
      cheeks. Short term (about 1 minute apart) and long term (mean 2.5 months apart)
      repeatability of Rint measurements (2 SDs of the mean paired difference between
      measurements) was also assessed in children referred for cough or wheeze.
      RESULTS: A total of 284 healthy white children (age range 3.0-6.4 years) were
      evaluated. Mean inspiratory and expiratory Rint (RintI and RintE) did not differ
      significantly in boys and girls. Age, height, and weight showed a significant
      inverse correlation with both RintI and RintE in the univariate analysis with
      linear regression. Multiple regression with age, height, and weight as the
      independent variables showed that all three variables were significantly and
      independently correlated with RintI, whereas only height was significantly and
      independently correlated with RintE. Supporting the cheeks had no significant
      effect on RintI (n=29, median 0.673 v 0.660 kPa/l.s, p=0.098) or RintE (n=39,
      median 0.702 v 0.713 kPa/l.s, p=0.126). Short term repeatability was 0.202
      kPa/l.s for RintI (n=50) and 0.242 kPa/l.s for RintE (n=69). Long term
      repeatability was 0.208 kPa/l.s for RintE (n=26). CONCLUSIONS: We have reported
      reference Rint values in preschool white children and have demonstrated the
      usefulness of this technique in assessing lung function in this age group.

PMID- 11514690
TI  - Enhanced survival of lung granulocytes in an animal model of asthma: evidence for
      a role of GM-CSF activated STAT5 signalling pathway.
AB  - BACKGROUND: As granulocyte/macrophage colony stimulating factor (GM-CSF) mediated
      delay of granulocyte apoptosis contributes to the accumulation of inflammatory
      cells at the site of inflammation in many diseases, we sought to determine
      whether asthma is also associated with a GM-CSF dependent increase in lung
      granulocyte survival. Moreover, because GM-CSF mediates its effects through
      activation of signal transducer and activator of transcription 5 (STAT5), we also
      investigated the potential role of STAT5 in allergic inflammation. METHODS: Blood
      granulocytes were recovered from six healthy and six heaves affected horses, a
      model of asthma. Lung granulocytes were obtained by bronchoalveolar lavage (BAL)
      from the same horses. Granulocytes were cultured in the presence or absence of
      anti-GM-CSF receptor antibodies for different times and apoptosis was determined
      using the Annexin-V/propidium iodide detection method. Nuclear protein extracts
      from cultured granulocytes were analysed for STAT5 binding activity by
      electrophoretic mobility shift assay. RESULTS: BAL fluid granulocytes from heaves
      affected horses demonstrated a significant delay in apoptosis compared with blood
      granulocytes from the same horses and blood and BAL fluid granulocytes from
      healthy horses. Conversely, the rate of apoptosis in blood granulocytes from
      healthy and heaves affected horses was comparable. The enhanced survival of BAL
      fluid granulocytes from affected horses was suppressed in the presence of
      antibodies directed against GM-CSF receptors. Increased levels of active STAT5
      were found in BAL fluid granulocytes from heaves affected horses and were
      markedly reduced after treatment with anti-GM-CSF receptor antibodies.
      CONCLUSIONS: These data indicate that granulocyte survival is enhanced in the
      lung of heaves affected horses and suggest a role for a GM-CSF activated STAT5
      pathway in delaying apoptosis of lung granulocytes in this model of asthma.

PMID- 11514691
TI  - Smoking cessation, decline in pulmonary function and total mortality: a 30 year
      follow up study among the Finnish cohorts of the Seven Countries Study.
AB  - BACKGROUND: Permanent smoking cessation reduces loss of pulmonary function. Less
      is known in the long term about individuals who give up smoking temporarily or
      quitters with lower initial pulmonary function. Little is known also about the
      relationship between decline in pulmonary function and mortality. We examined
      these aspects and the association between smoking, decline in pulmonary function,
      and mortality. METHODS: Two middle aged male Finnish cohorts of the Seven
      Countries Study and their re-examinations on five occasions during a 30 year
      period of follow up were analysed. RESULTS: During the first 15 years (n=1007)
      adjusted decline in forced expiratory volume in 0.75 seconds (FEV(0.75)) was 46.4
      ml/year in never smokers, 49.3 ml/year in past smokers, 55.5 ml/year in permanent
      quitters, 55.5 ml/year in intermittent quitters, and 66.0 ml/year in continuous
      smokers (p<0.001 for trend). Quitters across the entire range of baseline
      FEV(0.75) had a slower decline in FEV(0.75) than continuous smokers. Among both
      continuing smokers and never smokers, non-survivors had a significantly (p<0.001)
      more rapid decline in FEV(0.75) than survivors. The adjusted relative hazard for
      total mortality was 1.73 (95% confidence interval (CI) 1.41 to 2.11) and 1.24
      (95% CI 1.02 to 1.52) in the lowest and middle tertiles of decline in FEV(0.75).
      Never smokers, past smokers, and quitters had significantly lower total mortality
      than continuous smokers, partly because of their slower decline in FEV(0.75).
      CONCLUSION: These results highlight the positive effect of smoking cessation,
      even intermittent cessation, on decline in pulmonary function. Accelerated
      decline in pulmonary function was found to be a risk factor for total mortality.
      The beneficial effect of smoking cessation on mortality may partly be mediated
      through a reduced decline in pulmonary function.

PMID- 11514692
TI  - Non-invasive ventilation in acute exacerbations of chronic obstructive pulmonary
      disease: long term survival and predictors of in-hospital outcome.
AB  - BACKGROUND: Non-invasive ventilation (NIV) reduces the need for intubation and
      the mortality associated with an exacerbation of chronic obstructive pulmonary
      disease (COPD). This study aimed to identify factors that could be used to
      stratify patients according to their risk of requiring invasive mechanical
      ventilation. The second aim was to determine the long term survival of patients
      treated with and without NIV. METHODS: In this prospective multicentre randomised
      controlled trial 118 patients were allocated to standard treatment and 118 to NIV
      between November 1996 and September 1998. Arterial blood gas tensions and
      respiratory rate were recorded at enrolment and after 1 and 4 hours. Prognostic
      factors were identified using logistic regression analysis. All patients were
      followed until death or 1 January 1999. RESULTS: At enrolment the H(+)
      concentration (OR 1.22 per nmol/l, 95% CI 1.09 to 1.37, p<0.01) and PaCO2 (OR
      1.14 per kPa, 95% CI 1.14 to 1.81, p<0.01) were associated with treatment
      failure. Allocation to NIV was protective (OR 0.39, 95% CI 0.19 to 0.80). After 4
      hours of treatment improvement in acidosis (OR 0.89 per nmol/l, 95% CI 0.82 to
      0.97, p<0.01) and fall in respiratory rate (OR 0.92 per breaths/min, 95% CI 0.84
      to 0.99, p=0.04) were associated with success. Median length of survival was 16.8
      months in those treated with NIV and 13.4 months in those receiving standard
      treatment (p=0.12). The trend in improved survival was attributable to prevention
      of death during the index admission. CONCLUSION: Initial pH and hypercapnia can
      be used to stratify groups of patients according to their risk of needing
      intubation. NIV reduces this risk and progress should be monitored using change
      in respiratory rate and pH. The long term survival after NIV is sufficiently good
      to render treatment appropriate.

PMID- 11514693
TI  - Alternative methods for assessing bronchodilator reversibility in chronic
      obstructive pulmonary disease.
AB  - BACKGROUND: Bronchodilator reversibility testing is recommended in all patients
      with chronic obstructive pulmonary disease (COPD) but does not predict
      improvements in breathlessness or exercise performance. Two alternative ways of
      assessing lung mechanics-measurement of end expiratory lung volume (EELV) using
      the inspiratory capacity manoeuvre and application of negative expiratory
      pressure (NEP) during tidal breathing to detect tidal airflow limitation-do
      relate to the degree of breathlessness in COPD. Their usefulness as end points in
      bronchodilator reversibility testing has not been examined. METHODS: We studied
      20 patients with clinically stable COPD (mean age 69.9 (1.5) years, 15 men,
      forced expiratory volume in one second (FEV(1)) 29.5 (1.6)% predicted) with tidal
      flow limitation as assessed by their maximum flow-volume loop. Spirometric
      parameters, slow vital capacity (SVC), inspiratory capacity (IC), and NEP were
      measured seated, before and after nebulised saline, and at intervals after 5 mg
      nebulised salbutamol and 500 microg nebulised ipratropium bromide. The patients
      attended twice and the treatment order was randomised. RESULTS: Mean FEV(1), FVC,
      SVC, and IC were unchanged after saline but the degree of tidal flow limitation
      varied. FEV(1) improved significantly after salbutamol and ipratropium (0.11
      (0.02) l and 0.09 (0.02) l, respectively) as did the other lung volumes with
      further significant increases after the combination. Tidal volume and mean
      expiratory flow increased significantly after all bronchodilators but
      breathlessness fell significantly only after the combination treatment. The
      initial NEP score was unrelated to subsequent changes in lung volume.
      CONCLUSIONS: NEP is not an appropriate measurement of acute bronchodilator
      responsiveness. Changes in IC were significantly larger than those in FEV(1) and
      may be more easily detected. However, our data showed no evidence for separation
      of "reversible" and "irreversible" groups whatever outcome measure was adopted.

PMID- 11514694
TI  - Systemic anti-inflammatory mediators in COPD: increase in soluble interleukin 1
      receptor II during treatment of exacerbations.
AB  - BACKGROUND: The aim of this study was to test the hypothesis that the chronic
      inflammatory process present in chronic obstructive pulmonary disease (COPD) is
      due to a defective endogenous anti-inflammatory mechanism. METHODS: Systemic
      levels of the anti-inflammatory mediators soluble interleukin 1 receptor II (sIL
      1RII), soluble tumour necrosis factor receptor p55 (sTNF-R55) and sTNF-R75, and
      of C reactive protein (CRP) and lipopolysaccharide binding protein (LBP) were
      analysed in 55 patients with stable COPD (median forced expiratory volume in one
      second (FEV(1)) 34% predicted (range 15-78)) and compared with levels in 23
      control subjects. In addition, changes in these mediators were studied in 13
      patients with COPD (median FEV(1) 34% predicted (range 19-51)) during the first 7
      days in hospital with an exacerbation of the disease. RESULTS: Patients with
      stable COPD were characterised by a systemic inflammatory process indicated by an
      increased leucocyte count (7.2 (4.7-16.4) v 4.8 (3.5-8.3) x 10(9)/l), raised
      levels of CRP (11.8 (1.1-75.0) v 4.1 (0.6-75.0) microg/ml) and LBP (45.6 (8.1
      200.0) v 27.9 (14.1-71.5) microg/ml), and moderate increases in both sTNF-Rs. In
      contrast, the sIL-1RII level did not differ between patients and controls (4.53
      (2.09-7.60) v 4.63 (3.80-5.93) ng/ml). During treatment of disease exacerbations,
      systemic levels of both CRP (at day 3) and LBP (at day 7) were significantly
      reduced compared with day 1, whereas sIL-1RII levels increased. CONCLUSIONS:
      These data suggest an imbalance in systemic levels of pro- and anti-inflammatory
      mediators in patients with stable COPD. The increase in the anti-inflammatory
      mediator sIL-1RII during treatment of exacerbations may contribute to the
      clinical improvement.

PMID- 11514695
TI  - Continuous positive airway pressure for sleep apnoea/hypopnoea syndrome:
      usefulness of a 2 week trial to identify factors associated with long term use.
AB  - BACKGROUND: The sleep apnoea/hypopnoea syndrome (SAHS) is common and treatment
      with continuous positive airway pressure (CPAP) is effective. However, not all
      patients can cope with the demands of using mask positive pressure. Compliance
      can be improved with an intensive educational programme and patient support, but
      this is not practical in most centres given the large numbers of patients coming
      forward for treatment. Several studies have evaluated correlations between
      various parameters at diagnosis in order to anticipate patients' behaviour and to
      avoid the social and health implications of undertreated SAHS. We have evaluated
      the use of additional data derived during a 2 week home CPAP trial to identify
      factors associated with longer term use of CPAP and compliance. METHODS:
      Following a diagnostic study, 209 patients were offered a CPAP machine for a 2
      week home trial. After completing the trial, patients were reassessed and scored
      their overall satisfaction with CPAP treatment on a five point scale ranging from
      "much worse" to "much better" and an Epworth score relating to the loan period.
      Machine run time was recorded from the integral clock. These data were added to
      those available at diagnosis to construct models indicative of continuing CPAP
      and average nightly use at 1 year. RESULTS: 209 patients were offered the 2 week
      loan at least a year before June 1999 (90.9% men, mean (SD) age 51.0 (10.6)
      years, body mass index (BMI) 34.6 (7.7) kg/m(2), Epworth score 15 (IQR 11-18),
      apnoea/hypopnoea index (AHI) 38.1 (22.9) events/h). 153 patients (73.2%) opted to
      continue CPAP and 56 declined. One year later data were available for 187
      patients; 128 (68.5% on an intention to treat analysis) continued to use the
      machine with a mean use of 5.0 (2.4) hours/night. A logistic regression model
      indicated that mean CPAP use during the loan period and the overall satisfaction
      score accurately defined continuing CPAP and "satisfactory" CPAP use at 1 year.
      For patients with low machine use and no symptomatic improvement during the loan
      period, the addition of baseline AHI, baseline Epworth score, and the Epworth
      score at the end of the loan to the equation identifying factors associated with
      "satisfactory" CPAP use (mean >2 hours/night) improved the value of the model.
      CONCLUSION: Data derived from a 2 week CPAP trial are useful in identifying
      patients who will comply with CPAP treatment to 1 year. It can be used to
      identify patients with significant symptomatic disease who will struggle with
      CPAP and may benefit from additional education and support. High mean hourly use
      and a high degree of overall satisfaction during the loan period identified
      patients likely to use CPAP and be compliant with it at 1 year.

PMID- 11514696
TI  - Aerosolised iloprost improves pulmonary haemodynamics in patients with primary
      pulmonary hypertension receiving continuous epoprostenol treatment.
AB  - BACKGROUND: Continuous intravenous treatment with epoprostenol significantly
      improves pulmonary haemodynamics and survival in patients with primary pulmonary
      hypertension (PPH). Its beneficial effect, however, may be blunted due to adverse
      effects such as catheter sepsis and systemic hypotension. Recent investigations
      have shown that inhaled iloprost is effective in the treatment of PPH. Based on
      their different pharmacokinetics, we hypothesised that the combination of
      intravenous epoprostenol and inhaled iloprost would be more efficacious than
      epoprostenol alone during acute testing in patients with PPH. METHODS: The effect
      of a single dose of inhaled iloprost (30 microg total over 15 minutes) on
      pulmonary haemodynamics was examined in eight patients with PPH (initial non
      responders to nitric oxide) who had considerable adverse effects during treatment
      with epoprostenol. RESULTS: The combination of inhaled iloprost and intravenous
      epoprostenol significantly improved mean pulmonary artery pressure (MPAP),
      cardiac index (CI), mixed venous oxygen saturation (SvO2), and systemic arterial
      oxygen pressure (PaO2) compared with epoprostenol treatment alone. Mean systemic
      arterial pressure (MSAP) and pulmonary capillary wedge pressure (PCWP) remained
      unchanged. CONCLUSIONS: The pulmonary vasoreactivity shown by additional iloprost
      inhalation during effective epoprostenol treatment suggests that an improvement
      of treatment for pulmonary hypertension may be possible by combining vasoactive
      substances.

PMID- 11514697
TI  - Pulmonary hypertension, interstitial lung fibrosis, and lung iron deposition in
      thalassaemia major.
AB  - Although restrictive lung disease is the predominant abnormality of pulmonary
      function in patients with thalassaemia major (TM), its aetiology and its
      association with pulmonary hypertension (PH) detected in some patients with TM
      remains unknown. We report a patient with TM, iron overload, frequent pulmonary
      infections, and progressive severe precapillary PH over the previous 5 years. A
      severe restrictive pattern and interstitial lung fibrosis were revealed by
      pulmonary function tests and high resolution computed tomography, respectively.
      This presentation suggests that interstitial fibrosis may complicate lung
      involvement in TM and can significantly contribute to the development of PH.

PMID- 11514699
TI  - Inhaled steroids for COPD?

PMID- 11514700
TI  - Smoking cessation: effects on symptoms, spirometry and future trends in COPD.

PMID- 11514701
TI  - Airway hyperresponsiveness and COPD mortality.

PMID- 11514702
TI  - Why don't we give chest patients dietary advice?

PMID- 11514703
TI  - Factors affecting susceptibility and resistance to tuberculosis.

PMID- 11514704
TI  - Anticoagulation in patients with thromboembolic disease.

PMID- 11514705
TI  - 18-Fluorodeoxyglucose positron emission tomography (FDG-PET) and the staging of
      early lung cancer.

PMID- 11514706
TI  - Sleep apnoea and hypertension: proof at last?

PMID- 11514707
TI  - Ventilator induced lung injury and infection in the critically ill.

PMID- 11514708
TI  - Allergen exposure and the development of asthma.

PMID- 11514711
TI  - Imaging of viruses by atomic force microscopy.

PMID- 11514712
TI  - Characterization of a novel genital human papillomavirus by overlapping PCR:
      candHPV86 identified in cervicovaginal cells of a woman with cervical neoplasia.
AB  - A novel human papillomavirus (HPV), candHPV86, was cloned and characterized from
      cervicovaginal cells obtained from a 37-year-old Hispanic woman with cervical
      intraepithelial neoplasia grade 1 (CIN1) using an overlapping PCR technique.
      Primers were designed by phylogenetic alignment of closely related HPV genomes
      using the L1 fragment sequence amplified by GP5+/6+. The 7983 bp complete
      nucleotide sequence of the HPV genome was determined by sequence walking. A basic
      local alignment sequence tool (BLAST) homology search using the L1 open reading
      frame demonstrated that this HPV was most closely related to HPVHAN2294 (GenBank,
      AJ400628; 86% homology) and HPV84 (84% homology). candHPV86 was placed in the HPV
      genome homology group A3 by phylogenetic analyses. The overlapping PCR technique
      is applicable for characterizing the complete spectrum and variation of HPVs in a
      population.

PMID- 11514710
TI  - Low dose inhaled corticosteroids and the prevention of death from asthma.

PMID- 11514713
TI  - Genomic and evolutionary characterization of TT virus (TTV) in tupaias and
      comparison with species-specific TTVs in humans and non-human primates.
AB  - TT virus (TTV) was recovered from the sera of tupaias (Tupaia belangeri
      chinensis) by PCR using primers derived from the noncoding region of the human
      TTV genome, and its entire genomic sequence was determined. One tupaia TTV
      isolate (Tbc-TTV14) consisted of only 2199 nucleotides (nt) and had three open
      reading frames (ORFs), spanning 1506 nt (ORF1), 177 nt (ORF2) and 642 nt (ORF3),
      which were in the same orientation as the ORFs of the human prototype TTV
      (TA278). ORF3 was presumed to arise from a splicing of TTV mRNA, similar to
      reported human TTVs whose spliced mRNAs have been identified, and encoded a joint
      protein of 214 amino acids with a Ser-, Lys- and Arg-rich sequence at the C
      terminus. Tbc-TTV14 was less than 50% similar to previously reported TTVs of 3.4
      3.9 kb and TTV-like mini viruses (TLMVs) of 2.8-3.0 kb isolated from humans and
      non-human primates, and known animal circoviruses. Although Tbc-TTV14 has a
      genomic length similar to animal circoviruses (1.8-2.3 kb), Tbc-TTV14 resembled
      TTVs and TLMVs with regard to putative genomic organization and transcription
      profile. Conserved motifs were commonly observed in the coding and noncoding
      regions of the Tbc-TTV14 genome and in all TTV and TLMV genomes. Phylogenetic
      analysis revealed that Tbc-TTV14 is the closest to TLMVs, and is closer to TTVs
      isolated from tamarin and douroucouli than to TTVs isolated from humans and
      chimpanzees. These results indicate that tupaias are naturally infected with a
      new TTV species that has not been identified among primates.

PMID- 11514709
TI  - Complex interactions in complex traits: obesity and asthma.

PMID- 11514714
TI  - A novel method using baculovirus-mediated gene transfer for production of
      recombinant adeno-associated virus vectors.
AB  - The baculovirus Autographa californica multiple nucleopolyhedrosis virus causes
      non-productive infection in mammalian cells. Recombinant baculovirus therefore
      has the capability to transfer and express heterologous genes in these cells if a
      mammalian promoter governs the gene of interest. We have investigated the
      possibility of using baculovirus as a tool to produce recombinant adeno
      associated virus (rAAV). AAV has become increasingly popular as a vector for gene
      therapy and functional genomics efforts, although its use is hampered by the lack
      of a simple and efficient vector production method. We show here that co
      infection of mammalian producer cells with three viruses - a baculovirus
      containing the reporter gene flanked by AAV ITRs, a baculovirus expressing the
      AAV rep gene and a helper adenovirus expressing the AAV cap gene - produces
      infectious rAAV particles. This baculovirus-based chimeric vector method may in
      future improve large-scale rAAV vector preparations and circumvent present-day
      problems associated with rAAV production.

PMID- 11514715
TI  - Efficient downregulation of major histocompatibility complex class I molecules in
      human epithelial cells infected with cytomegalovirus.
AB  - Liver and intestinal epithelial cells are a major target of infection by
      cytomegaloviruses (CMV), causing severe disease in affected organs of
      immunocompromised patients. CMV downregulates major histocompatibility complex
      class I (MHC-I) molecule expression in fibroblasts in order to avoid lysis by
      CD8(+) cytotoxic T lymphocytes. However, MHC-I expression in human
      cytomegalovirus (HCMV)-infected hepatic tissue was reported to be increased. As
      it is unclear at present whether HCMV affects MHC-I expression in epithelial
      cells, new cell culture models for HCMV infection of differentiated hepatobiliary
      cell lines were established. HCMV immediate early gene expression was achieved in
      60 to 95% of cells. Progression of the HCMV replication cycle differed from
      prototypic infection of fibroblasts, since structural early and late proteins
      were produced at low levels and HCMV progeny yielded much lower titres in
      hepatobiliary cells. In contrast, HCMV glycoproteins, gpUS2, gpUS3, gpUS6 and
      gpUS11, that downregulate MHC-I expression were synthesized with temporal
      kinetics and in a similar quantity to that seen in fibroblasts. As a result, HCMV
      infection led to a drastic and selective downregulation of MHC-I expression in
      epithelial cells and was uniformly observed irrespective of the hepatic or
      biliary origin of the cells. The new models document for the first time a stealth
      function of HCMV in epithelial cells and indicate that the downregulation of MHC
      I expression by HCMV can occur in the virtual absence of virus replication.

PMID- 11514716
TI  - The UL41-encoded virion host shutoff (vhs) protein and vhs-independent mechanisms
      are responsible for down-regulation of MHC class I molecules by bovine
      herpesvirus 1.
AB  - The virion host shutoff (vhs) protein of alphaherpesviruses causes a rapid
      shutoff of host cell protein synthesis. We constructed a bovine herpesvirus 1
      (BHV1) deletion mutant in which the putative vhs gene, UL41, has been disrupted.
      Whereas protein synthesis is inhibited within 3 h after infection with wild-type
      BHV1, no inhibition was observed after infection with the BHV1(vhs-) deletion
      mutant. These results indicate that the BHV1 UL41 gene product is both necessary
      and sufficient for shutoff of host cell protein synthesis at early times post
      infection. Using the vhs deletion mutant, we investigated the mechanism of BHV1
      induced down-regulation of MHC class I cell surface expression. In contrast to
      BHV1 wild-type infection, the BHV1(vhs-) mutant allows detection of MHC class I
      molecules at much later time-points after infection. This illustrates the role
      the vhs protein plays in MHC class I down-regulation. However, even after
      infection with BHV1(vhs-), MHC class I cell surface expression is impaired. In
      BHV1(vhs-)-infected cells, MHC class I molecules are retained within the
      endoplasmic reticulum (ER). Moreover, the transporter associated with antigen
      presentation (TAP) is still blocked. Temporal control of viral protein expression
      using chemical inhibitors shows that viral protein(s) expressed within the early
      phase of BHV1 infection are responsible for ER retention of MHC class I
      molecules. These results indicate that multiple mechanisms are responsible for
      down-regulation of MHC class I molecules in BHV1-infected cells.

PMID- 11514717
TI  - Vaccinia virus semaphorin A39R is a 50-55 kDa secreted glycoprotein that affects
      the outcome of infection in a murine intradermal model.
AB  - Vaccinia virus (VV) protein A39R has amino acid similarity to the extracellular
      domain of a glycosylphosphatidylinositol-linked cell surface semaphorin
      (SEMA7A/CDw108) that has an immunological expression profile and binding
      properties, thereby implicating A39R as an immunomodulator. Previously, a closely
      related A39R protein expressed by ectromelia virus was shown to induce cytokine
      production and up-regulate ICAM-1 expression in mouse monocytes in vitro. In this
      study, we show that the A39R gene of VV strain Copenhagen (COP) encodes a 50-55
      kDa secreted glycoprotein and is expressed late during infection. The A39R
      protein was secreted by eight of 15 strains of VV, but not by strain Western
      Reserve (WR). To analyse the VV A39R function, several recombinant viruses were
      made, including an A39R deletion mutant of VV COP and a WR mutant containing the
      A39R sequence from COP. Loss of the gene from COP did not affect virus growth in
      vitro, or VV virulence in a mouse intranasal model, and had only a slight effect
      on lesion size in an intradermal model. In contrast, expression of COP A39R by VV
      WR was associated with an increase in the severity and persistence of skin
      lesions after intradermal infection of mice. Finally, a histological examination
      of mouse skin infected with recombinant viruses suggested that A39R has direct or
      indirect pro-inflammatory properties.

PMID- 11514718
TI  - The vaccinia virus A41L protein is a soluble 30 kDa glycoprotein that affects
      virus virulence.
AB  - Vaccinia virus (VV) gene A41L encodes an acidic protein with amino acid
      similarity to the 35 kDa protein of VV strain Lister, a soluble protein called
      vCKBP that binds CC chemokines, and to a protein from orf virus, called GIF, that
      binds GM-CSF and IL-2. However, despite the similarity, recombinant A41L protein
      was found not to bind these ligands or a variety of other chemoattractant
      molecules when tested using surface plasmon resonance. The A41L gene is expressed
      early and late during infection and encodes a 30 kDa protein that contains both N
      and O-linked carbohydrate and is secreted from the infected cell. All 16 strains
      of VV and 2 strains of cowpox virus that were tested express the A41L protein,
      implying it has an important function for orthopoxviruses. Nonetheless, a VV
      strain Western Reserve deletion mutant lacking the A41L gene (vDeltaA41L) formed
      normal sized plaques and replicated to the same titre as wild-type and revertant
      viruses. The importance of the A41L protein in vivo was demonstrated in a mouse
      intradermal model in which infection with vDeltaA41L caused more severe lesions
      compared to wild-type and revertant viruses. Further examination in this model
      revealed that deletion of A41L enhanced clearance of infectious virus, suggesting
      that A41L expression reduces immunopathology. Consistent with this, histological
      examination of infected rabbit skin showed that the A41L protein could reduce the
      infiltration of inflammatory cells into the infected area. Together, these data
      suggest that the A41L protein constitutes a novel immunomodulatory protein.

PMID- 11514719
TI  - Construction and characterization of recombinant vaccinia viruses co-expressing a
      respiratory syncytial virus protein and a cytokine.
AB  - Recombinant vaccinia viruses are well-characterized tools that can be used to
      define novel approaches to vaccine formulation and delivery. While vector co
      expression of immune mediators has enormous potential for optimizing the
      composition of vaccine-induced immune responses, the impact on antigen expression
      and vector antigenicity must also be considered. Co-expression of IL-4 increased
      vaccinia virus vector titres, while IFN-gamma co-expression reduced vaccinia
      virus replication in BALB/c mice and in C57BL/6 mice infected with some
      recombinant viruses. Protection against respiratory syncytial virus (RSV)
      challenge was similar in mice immunized with vaccinia virus expressing RSV G
      glycoprotein and IFN-gamma, even though the replication efficiency of the vector
      was diminished. These data demonstrate the ability of vector-expressed cytokine
      to influence the virulence of the vector and to direct the development of
      selected immune responses. This suggests that the co-expression of cytokines and
      other immunomodulators has the potential to improve the safety of vaccine vectors
      while improving the immunogenicity of vaccine antigens.

PMID- 11514720
TI  - Genetic diversity and molecular epidemiology of respiratory syncytial virus over
      four consecutive seasons in South Africa: identification of new subgroup A and B
      genotypes.
AB  - The molecular epidemiology of respiratory syncytial virus (RSV) was studied over
      four consecutive seasons (1997-2000) in a single tertiary hospital in South
      Africa: 225 isolates were subgrouped by RT-PCR and the resulting products
      sequenced. Subgroup A predominated in two seasons, while A and B co-circulated
      approximately equally in the other seasons. The nucleotide sequences of the C
      terminal of the G-protein were compared to sequences representative of previously
      defined RSV genotypes. South African subgroup A and subgroup B isolates clustered
      into four and five genotypes respectively. One new subgroup A and three new
      subgroup B genotypes were identified. Different genotypes co-circulated in every
      season. Different circulation patterns were identified for group A and B
      isolates. Subgroup A revealed more variability and displacement of genotypes
      while subgroup B remained more consistent.

PMID- 11514721
TI  - Differential permissivity to measles virus infection of human and CD46-transgenic
      murine lymphocytes.
AB  - Analysis of measles virus (MV) pathogenesis requires the development of an
      adequate small animal model of MV infection. In this study, permissivity to MV
      infection was compared in human and transgenic murine T lymphocytes, expressing
      different levels of the human MV receptor, CD46. Whereas MV binding and entry
      correlated with CD46 expression, higher levels of MV replication were always
      observed in human T lymphocytes. This suggests the existence of intracellular
      factors, acting posterior to virus entry, that could limit MV replication in
      murine lymphocytes and should be considered when creating new animal models of MV
      infection.

PMID- 11514722
TI  - A measles virus glycoprotein-derived human CTL epitope is abundantly presented
      via the proteasomal-dependent MHC class I processing pathway.
AB  - Peptides derived from measles virus (MV) are presented by MHC class I molecules
      at widely divergent levels, but it is currently unknown how functional these
      levels are. Here, for the first time, we studied the natural occurrence and the
      underlying processing events of a known MV CTL epitope derived from the fusion
      glycoprotein (MV-F) and restricted via HLA-B*2705. Using MHC-peptide elution of
      MV-infected cells followed by sensitive mass spectrometry we determined the
      naturally occurring sequence to be RRYPDAVYL, corresponding to MV-F(438-446). Its
      level of expression was enumerated at approximately 1500 copies per cell, which
      is considered to be abundant, but lies within the range described for other viral
      CTL epitopes in human MHC class I molecules. We found that processing of the MV
      F(438-446) epitope occurs primarily via the classic MHC class I loading pathway,
      since presentation to CTL depends on both the transporter associated with antigen
      presentation (TAP) and the proteasome. Even though it is cotranslationally
      inserted into the ER, a major part of MV-F is located in the cytosol, where it
      accumulates rapidly in the presence of proteasome inhibitors. We therefore
      conclude that a substantial cytosolic turnover of MV-F, together with some
      excellent processing features of MV-F(438-446) precursors, such as precise C
      terminal excision by proteasomes, efficient TAP transport and strong HLA binding,
      dictate the abundant functional expression of the MV-F(438-446) CTL epitope in
      HLA-B*2705 at the surface of MV-infected cells.

PMID- 11514723
TI  - Leucine at position 278 of the AIK-C measles virus vaccine strain fusion protein
      is responsible for reduced syncytium formation.
AB  - The live measles virus (MV) vaccine strain AIK-C was attenuated from the wild
      type strain Edmonston by plaque purification at 33 degrees C. Strain AIK-C grew
      well at 33 degrees C with a mixture of small-and medium-sized plaques in Vero
      cells, but did not grow well at 40 degrees C. To investigate fusion inducibility,
      expression plasmids for the fusion (F) and haemagglutinin (H) protein regions of
      MV strains AIK-C (pAIK-F01 and pAIK-H) and Edmonston (pEdm-F and pEdm-H) were
      constructed. pEdm-F induced extensive cell fusion in B95a and Vero cells under
      the control of T7 RNA polymerase, whereas a sharp reduction in syncytium
      formation was observed when pAIK-F01 was used. Six amino acid differences were
      determined between pAIK-F01 and pEdm-F. Direct sequencing showed that the seed
      strain AIK-C contained either Leu or Phe at position 278 of the F protein.
      Experiments using recombinant F protein plasmids demonstrated that those with Leu
      at position 278 induced poor syncytium formation, while those with Phe at
      position 278 (Edmonston type) induced extensive cell fusion. Replacement of Phe
      with Leu at position 278 of pEdm-F reduced fusion-inducing capability. A full
      length infectious clone of AIK-C with Leu at position 278 of the F protein was
      constructed. The rescued virus produced small plaques in Vero cells. However, the
      same rescued virus with Phe at position 278 produced large plaques. It was
      concluded that Leu at position 278 of the F protein of the MV vaccine strain AIK
      C is responsible for the formation of small plaques.

PMID- 11514724
TI  - Complete nucleotide sequences of Nipah virus isolates from Malaysia.
AB  - We have completely sequenced the genomes of two Nipah virus (NiV) isolates, one
      from the throat secretion and the other from the cerebrospinal fluid (CSF) of the
      sole surviving encephalitic patient with positive CSF virus isolation in
      Malaysia. The two genomes have 18246 nucleotides each and differ by only 4
      nucleotides. The NiV genome is 12 nucleotides longer than the Hendra virus (HeV)
      genome and both genomes have identical leader and trailer sequence lengths and
      hexamer-phasing positions for all their genes. Both NiV and HeV are also very
      closely related with respect to their genomic end sequences, gene start and stop
      signals, P gene-editing signals and deduced amino acid sequences of nucleocapsid
      protein, phosphoprotein, matrix protein, fusion protein, glycoprotein and RNA
      polymerase. The existing evidence demonstrates a clear need for the creation of a
      new genus within the subfamily Paramyxovirinae to accommodate the close
      similarities between NiV and HeV and their significant differences from other
      members of the subfamily.

PMID- 11514725
TI  - Complete nucleotide sequence of avian paramyxovirus type 6 isolated from ducks.
AB  - There are nine serotypes of avian paramyxovirus (APMV). Only the genome of APMV
      type 1 (APMV-1), also called Newcastle disease virus (NDV), has been completely
      sequenced. In this study, the complete nucleotide sequence of an APMV-6 serotype
      isolated from ducks is reported. The 16236 nt genome encodes eight proteins,
      nucleocapsid protein (NP), phosphoprotein (P), V protein, matrix protein (M),
      fusion protein (F), small hydrophobic (SH) protein, haemagglutinin-neuraminidase
      (HN) protein and large (L) protein, which are flanked by a 55 nt leader sequence
      and a 54 nt trailer sequence. Sequence comparison reveals that the protein
      sequences of APMV-6 are most closely related to those of APMV-1 (NDV) and -2,
      with sequence identities ranging from 22 to 44%. However, APMV-6 contains a gene
      that might encode the SH protein, which is absent in APMV-1, but present in the
      rubulaviruses simian virus type 5 and mumps virus. The presence of an SH gene in
      APMV-6 might provide a link between the evolution of APMV and rubulaviruses.
      Phylogenetic analysis demonstrates that APMV-6, -1, -2 (only the F and HN
      sequences were available for analysis) and -4 (only the HN sequences were
      available for analysis) all cluster into a single lineage that is distinct from
      other paramyxoviruses. This result suggests that APMV should constitute a new
      genus within the subfamily Paramyxovirinae.

PMID- 11514726
TI  - Antigenic variants with amino acid deletions clarify a neutralizing epitope
      specific for influenza B virus Victoria group strains.
AB  - To study the neutralizing epitopes of influenza B virus Victoria group strains,
      two monoclonal antibodies (MAbs) were used to select antigenic variants of the
      virus. MAbs 10B8 and 8E6 were found to react with B/Victoria group strains in
      three tests, peroxidase-antiperoxidase staining, haemagglutination inhibition and
      neutralization tests; no reactivity with B/Yamagata group strains was observed.
      Analysis of the deduced amino acid sequences of 10B8-induced variants identified
      a single amino acid deletion at residue 165 or 170, as well as a single amino
      acid substitution at residues 164 (Asp-->Tyr), 165 (Asn-->Ser or Thr) or 203 (Lys
      ->Thr or Asn). A single amino acid substitution at residue 241 (Pro-->Ser) was
      observed in 8E6-induced variants. Three-dimensional analysis showed that the
      epitopes for both MAbs were situated in close proximity to each other. Since
      B/Yamagata group strains are characterized by amino acid deletions at residues
      164-166, the epitope for MAb 10B8 is strictly specific for B/Victoria group
      strains.

PMID- 11514727
TI  - Phylogeny of the Simbu serogroup of the genus Bunyavirus.
AB  - The Simbu serogroup of the genus Bunyavirus, family Bunyaviridae contains 25
      viruses. Previous serological studies provided important information regarding
      some but not all of the relationships among Simbu serogroup viruses. This report
      describes the nucleotide sequence determination of the nucleocapsid (N) gene of
      the small genomic segment of 14 Simbu serogroup viruses and partial nucleotide
      sequence determination of the G2 glycoprotein-coding region (encoded by the
      medium RNA segment) of 19 viruses. The overall phylogeny of the Simbu serogroup
      inferred from analyses of the N gene was similar to that inferred from analyses
      of the G2 protein-coding region. Both analyses revealed that the Simbu serogroup
      viruses have evolved into at least five major phylogenetic lineages. In general,
      these phylogenetic lineages were consistent with the previous serological data,
      but provided a more detailed understanding of the relatedness amongst many
      viruses. In comparison to previous phylogenetic studies on the California and
      Bunyamwera serogroups of the Bunyavirus genus, the Simbu serogroup displays much
      larger genetic variation in the N gene (up to 40% amino acid sequence
      divergence).

PMID- 11514728
TI  - Characterization of hepatitis D virus genotype III among Yucpa Indians in
      Venezuela.
AB  - The complete genome sequences of hepatitis D virus (HDV) strains isolated from
      three Yucpa Amerindians in Venezuela were determined and found to be genotype
      III. Comparison of these three genotype III sequences demonstrated the presence
      of a hypervariable region containing numerous substitutions, insertions/deletions
      and a highly conserved region containing the self-cleavage domains, which have
      been reported previously for genotypes I and II. Amino acid changes within the
      first 90 amino acids of the hepatitis D antigen (HDAg) were found in the genotype
      III sequences, while the remainder of the HDAg-coding sequence was conserved. The
      secondary structure for the RNA-editing site differed between genotypes I and
      III. It was concluded that the serious delta hepatitis outbreaks characterized
      epidemiologically in the Yucpa Amerindians were caused by HDV genotype III
      isolates that were related to HDV genotype III isolates from other regions of
      South America.

PMID- 11514729
TI  - Immunogenicity of an E1-deleted recombinant human adenovirus against rabies by
      different routes of administration.
AB  - The immunogenic properties of an E1-deleted, human adenovirus type 5 (Ad5)
      vaccine virus with activity against rabies were examined in mice, foxes and dogs
      using different routes of administration. NMRI mice received 10(5.8), 10(5.3),
      10(4.3), 10(3.3) and 10(2.3) TCID(50) by peroral or intramuscular (i.m.)
      administration. Furthermore, six mice received 10(5.8) TCID(50) intracerebrally
      (i.c.). The construct elicited marked seroconversion in mice after oral
      administration. Immunoreactivity in mice was even more pronounced i.m. and i.c.
      After direct oral administration (10(8.0) TCID(50)) in foxes, six of eight
      animals developed rabies virus-neutralizing antibodies (VNA). All foxes immunized
      by direct injection (10(7.7) TCID(50)) in the membrane of the jejunum were shown
      to seroconvert. Pre-existing immunity against canine adenovirus did not hinder
      the development of rabies VNA after oral application of the construct (10(8.0)
      TCID(50)). Fox cubs (24-29 days old) born from rabies-immune vixens were shown to
      develop very high levels of rabies VNA after i.m. administration (10(8.0)
      TCID(50)), indicating that the immunogenicity of the construct could surpass
      maternally transferred immunity. In dogs, the construct (10(8.0) TCID(50))
      induced a very strong immune response after i.m. administration. However, no
      immune response was detectable in dogs after direct oral administration (10(8.3)
      TCID(50)) or after endoscopic deposition in the smaller intestine (10(8.0)
      TCID(50)). Hence, it must be concluded that the construct is not suitable for
      oral vaccination of dogs against rabies.

PMID- 11514730
TI  - Evidence of Borna disease virus genome detection in French domestic animals and
      in foxes (Vulpes vulpes).
AB  - Borna disease virus (BDV) is an enveloped, non-segmented negative-stranded RNA
      virus which belongs to the Bornaviridae family. BDV is an aetiological agent of
      encephalitis in horses, sheep and several other vertebrate species. In order to
      extend our knowledge about the presence of BDV in France, a study based on BDV
      RNA detection by RT-nested-PCR was done with 196 animal tissues: 171 brain
      samples collected from different animal species (75 horses, 59 foxes, 31 cattle,
      4 dogs, 1 sheep, 1 roe deer) and 25 horse blood samples. An RNA internal standard
      molecule was constructed and was co-amplified with the test template. This study
      reports the first detection of BDV RNA in France in 10 brain samples collected
      from horses, foxes and cattle, and from 14 horse blood samples. Detection of the
      BDV genome in the brains of six red foxes is the first evidence of BDV infection
      in this species.

PMID- 11514731
TI  - A PCR primer system for detecting oncoretroviruses based on conserved DNA
      sequence motifs of animal retroviruses and its application to human leukaemias
      and lymphomas.
AB  - Many C- and D-type retroviruses are known to cause a broad spectrum of malignant
      diseases in animals. Certain genome regions of these animal retroviruses are
      highly conserved between different animal species. It should be possible to
      detect new members of the retrovirus family with consensus PCR primers derived
      from these conserved sequence motifs. The consensus PCR primers developed in this
      study are generic enough to detect nearly all known oncogenic mammalian and avian
      exogenous C- and D-type retroviruses but do not amplify human endogenous
      retroviral sequences. In contrast to previous investigations, the present study
      involved highly stringent PCR conditions and truly generic PCR primers. Forty
      four samples from patients with various immunophenotyped malignant diseases
      (acute and chronic T-/B-cell lymphocytic leukaemias, acute myeloid leukaemias, T
      /B-cell lymphomas, chronic myeloproliferative disorders) and three cell lines
      (Hodgkin's lymphoma, Burkitt's lymphoma) have thus far been investigated using
      these PCR primers. The fact that no retroviruses have been found argues against
      an involvement of known animal oncoretroviruses or related hitherto undetected
      human retroviruses in the aetiopathogenesis of these diseases. The retrovirus
      detection system developed here may be used to confirm suspected retroviral
      involvement in other (malignant or nonmalignant) human diseases as well as to
      identify new animal retroviruses.

PMID- 11514732
TI  - Induction of simian immunodeficiency virus (SIV)-specific CTL in rhesus macaques
      by vaccination with modified vaccinia virus Ankara expressing SIV transgenes:
      influence of pre-existing anti-vector immunity.
AB  - A major aim in AIDS vaccine development is the definition of strategies to
      stimulate strong and durable cytotoxic T lymphocyte (CTL) responses. Here we
      report that simian immunodeficiency virus (SIV)-specific CTL developed in 4/4
      macaques following a single intramuscular injection of modified vaccinia virus
      Ankara (MVA) constructs expressing both structural and regulatory/accessory genes
      of SIV. In two animals Nef-specific responses persisted, but other responses
      diminished and new responses were not revealed, following further vaccination.
      Vaccination of another two macaques, expressing Mamu A*01 MHC class I, with MVA
      constructs containing nef and gag-pol under the control of the moderate strength
      natural vaccinia virus early/late promoter P7.5, again induced an early Nef
      specific response, whereas responses to Gag remained undetectable. Anti-vector
      immunity induced by this immunization was shown to prevent the efficient
      stimulation of CTL directed to the cognate Gag epitope, p11C C-M, following
      vaccination with another MVA construct expressing SIV Gag-Pol under a strong
      synthetic vaccinia virus-specific promoter. In contrast, vaccination of a
      previously unexposed animal resulted in a SIV-specific CTL response widely
      disseminated in lymphoid tissues including lymph nodes associated with the rectal
      and genital routes of SIV entry. Thus, despite the highly attenuated nature of
      MVA, repeated immunization may elicit sufficient anti-vector immunity to limit
      the effectiveness of later vaccination.

PMID- 11514733
TI  - In situ hybridization and immunolabelling study of the early replication of
      simian immunodeficiency virus (SIVmacJ5) in vivo.
AB  - The distribution of virus-infected cells in cynomolgus macaques was determined at
      4, 7, 14 and 28 days following intravenous challenge with 1000 TCID(50) of the
      wild-type simian immunodeficiency virus SIVmacJ5 (stock J5C). At each time-point,
      pairs of macaques were killed humanely and the presence of SIV was determined and
      quantified in blood, spleen, peripheral and mesenteric lymph nodes, thymus, lung
      and ileum by virus co-cultivation with C8166 cells, by quantitative DNA PCR or by
      in situ hybridization (ISH). At day 4 post-infection (p.i.), detection of the
      virus was sporadic. By day 7 p.i., however, significant SIV loads were detected
      in the blood and lymphoid tissues by DNA PCR and virus co-cultivation. Large
      numbers of cells expressing SIV RNA were detected in mesenteric lymph nodes by
      ISH and significantly fewer (P<0.05) in the spleen. Significant numbers of ISH
      positive cells were also observed in sections of ileum. By day 14 p.i., the
      distribution of SIV was more even in all lymphoid tissues analysed. By day 28,
      most of the tissues were negative by ISH, but all remained positive by virus
      isolation and DNA PCR. Immunolabelling of sections of mesenteric lymph node with
      monoclonal antibodies specific for SIV envelope and Nef largely confirmed the
      observations from ISH. These results indicate that, even following intravenous
      challenge, a major site of the initial replication of SIV is gut-associated
      lymphoid tissue. Vaccines that induce protection at this site may therefore be
      superior, even against parenteral challenge.

PMID- 11514734
TI  - p53-dependent transcriptional repression of p21(waf1) by hepatitis C virus NS3.
AB  - Hepatitis C virus (HCV) NS3 protein is known to affect normal cellular functions,
      such as cell proliferation and cell death, and to be involved, either directly or
      indirectly, in HCV hepatocarcinogenesis. In this study, we demonstrated that NS3
      protein could specifically repress the promoter activity of p21 in a dose
      dependent manner. The effect was not cell type-specific and was synergistic when
      combined with HCV core protein. Repression of the p21 promoter by NS3 was almost
      completely lost when p53 binding sites present on the p21 promoter were removed.
      Furthermore, p53 binding sites were sufficient to confer a strong NS3
      responsiveness to an heterologous promoter, suggesting that NS3 represses the
      transcription of p21 by modulating the activity of p53. Although the NS3 protein
      domain required for the majority of p21 repression was located on the protease
      domain, the proteinase activity itself does not seem to be necessary for
      repression. Both transcription and protein stability of p53 were unaffected by
      NS3, suggesting that NS3 might repress transcription of p21 by inhibiting the
      regulatory activity of p53 via protein-protein interaction(s). Finally, the
      growth rate of NS3-expressing cell lines was at least twice as fast as that of
      the parent NIH 3T3 cells, indicating that the repression of p21 is actually
      reflected by the stimulation of cell growth.

PMID- 11514735
TI  - Mutagenesis of hepatitis C virus E1 protein affects its membrane-permeabilizing
      activity.
AB  - The E1 glycoprotein of hepatitis C virus is a transmembrane glycoprotein with a C
      terminal anchor domain. When expressed in Escherichia coli, E1 induces a change
      in membrane permeability that is toxic to the bacterial cell. The C-terminal
      hydrophobic region (aa 331-383) of E1 is mainly responsible for membrane
      association and for inducing changes in membrane permeability. These observed
      changes are similar to those produced in E. coli by influenza virus M2, human
      immunodeficiency virus gp41 and poliovirus 3AB proteins, whose hydrophobic
      domains are thought to cause pore formation in biological membranes. To further
      characterize the activity of E1 at a molecular level, the membrane-permeabilizing
      ability of a second internal hydrophobic region (aa 262-291) was examined by
      expressing different deletion mutants of E1 in an E. coli system that is widely
      used for analysing membrane-active proteins from other animal viruses. Moreover,
      highly conserved amino acids in the C-terminal hydrophobic region were mutated to
      identify residues that are critical for inducing changes in membrane
      permeability. Analysis of cell growth curves of recombinant cultures and membrane
      permeability assays revealed that synthesis of this fragment increased the flux
      of small compounds through the membrane and caused progressive cell lysis,
      suggesting that this domain has membrane-active properties. Furthermore, analysis
      of C-terminal mutants indicated that the conserved amino acids Arg(339), Trp(368)
      and Lys(370) play a critical role in protein function, as both cell lysis and
      changes in membrane permeability induced by the wild-type clone could be blocked
      by substitutions in these positions.

PMID- 11514736
TI  - Determination of the intramolecular disulfide bond arrangement and biochemical
      identification of the glycosylation sites of the nonstructural protein NS1 of
      Murray Valley encephalitis virus.
AB  - The 12 cysteine residues in the flavivirus NS1 protein are strictly conserved,
      suggesting that they form disulfide bonds that are critical for folding the
      protein into a functional structure. In this study, we examined the
      intramolecular disulfide bond arrangement of NS1 of Murray Valley encephalitis
      virus and elucidated three of the six cysteine-pairing arrangements. Disulfide
      linkages were identified by separating tryptic-digested NS1 by reverse-phase high
      pressure liquid chromatography and analysing the resulting peptide peaks by
      protein sequencing, amino acid analysis and/or electrospray mass spectrometry.
      The pairing arrangements between the six amino-terminal cysteines were identified
      as follows: Cys(4)-Cys(15), Cys(55)-Cys(143) and Cys(179)-Cys(223). Although the
      pairing arrangements between the six carboxy-terminal cysteines were not
      determined, we were able to eliminate several cysteine-pairing combinations.
      Furthermore, we demonstrated that all three putative N-linked glycosylation sites
      of NS1 are utilized and that the Asn(207) glycosylation site contains a mannose
      rich glycan.

PMID- 11514737
TI  - The novel picornavirus Equine rhinitis B virus contains a strong type II internal
      ribosomal entry site which functions similarly to that of Encephalomyocarditis
      virus.
AB  - Equine rhinitis B virus (ERBV) has recently been classified as an Erbovirus, a
      new genus in the Picornaviridae family. ERBV is distantly related to members of
      the Cardiovirus and Aphthovirus genera which utilize a type II internal ribosome
      entry sequence (IRES) to initiate translation. We show that ERBV also possesses
      the core stem-loop structures (H-L) of a type II IRES. The function of the ERBV
      IRES was characterized using bicistronic plasmids that were analysed both by
      transfection into BHK-21 cells and by in vitro transcription and translation in
      rabbit reticulocyte lysates. In both systems, a region encompassed by nucleotides
      (nt) 189-920 downstream of the poly(C) tract was required for maximal
      translation. This sequence includes stem-loops H-L as well as four additional
      upstream stem-loops. Nt 904 corresponds to the second of three in-frame AUG
      codons located immediately downstream of the polypyrimidine tract (nucleotides
      869-880). Site-directed mutagenesis demonstrated that AUG2 is the major
      initiation codon despite the appropriate positioning of AUG1 16 nt downstream of
      the polypyrimidine tract. In direct IRES competition experiments, the ERBV IRES
      was able to compete strongly for translation factors with the IRES of
      Encephalomyocarditis virus (EMCV). This was true when the assays were performed
      in vitro (with the IRESs competing either in cis or trans) and in vivo (with the
      IRESs competing in cis). A comparative analysis of the strength of several IRESs
      revealed that the ERBV IRES, like that of the EMCV, is a powerful inducer of
      translation and may have similar potential for use in mammalian expression
      systems.

PMID- 11514738
TI  - Distribution of rotavirus-specific memory B cells in gut-associated lymphoid
      tissue after primary immunization.
AB  - We found previously that mice inoculated orally with simian rotavirus strain RRV
      developed virus-specific memory B cell responses 16 weeks after immunization that
      were greater than those found 6 weeks after immunization. Memory B cell responses
      were defined as the quantity of virus-specific IgA detected in small intestinal
      lamina propria (LP) fragment cultures of immunized mice at various intervals
      after challenge. Enhanced memory B cell responses correlated with enhanced
      protection against shedding. In order to understand better the delayed onset of
      rotavirus-specific memory B cell responses, a method was developed to determine
      the frequencies of rotavirus-specific memory B cells in gut-associated lymphoid
      tissues (GALT). We found that protection against rotavirus challenge was
      determined by the frequency of rotavirus-specific memory B cells in GALT LP.

PMID- 11514739
TI  - Coat protein gene-mediated resistance to Potato virus A in transgenic plants is
      suppressed following infection with another potyvirus.
AB  - High levels of resistance to Potato virus A (PVA, genus Potyvirus), indicated by
      absence of detectable infection in inoculated leaves, were attained in Nicotiana
      benthamiana transformed with a construct expressing the PVA 5'-untranslated
      region fused with the coat protein (CP)-encoding sequence. Low steady-state
      levels of the transgene transcripts were detected. Resistance was PVA-specific
      and did not protect the plants against infection with Potato virus Y (PVY, genus
      Potyvirus). Consequently, the steady-state levels of the CP-transgene mRNA were
      greatly elevated in the plants infected with PVY, and plants became susceptible
      to infection with PVA. These data show that virus resistance obtained by
      expressing regions of a plant virus genome in transgenic plants may be suppressed
      following infection with another virus that evades the virus-specific resistance.

PMID- 11514740
TI  - A study of the Autographa californica multiple nucleopolyhedrovirus ODV envelope
      protein p74 using a GFP tag.
AB  - The Autographa californica multiple nucleopolyhedrovirus (AcMNPV) protein p74 is
      associated with the occlusion-derived virus (ODV) envelope. p74 is essential for
      oral infectivity of ODV and has been proposed to play a role in midgut attachment
      and/or fusion. In this study, p74 protein was expressed in-frame with green
      fluorescent protein (GFP) to create a p74-GFP chimera. The C-terminal GFP portion
      of the chimera facilitated visualization of the trafficking of p74 in baculovirus
      infected Spodoptera frugiperda (Sf-9) cells. p74-GFP chimeric proteins localized
      in the intranuclear ring zone of the nucleus and were found to co-precipitate
      with the microvesicle fraction of cell lysates. A series of truncations of p74
      was expressed as p74-GFP chimeras in recombinant baculoviruses. When C-terminal
      region S580-F645 was deleted from p74, p74-GFP chimera localization became non
      specific and chimeras became soluble. p74 region S580-F645 directed GFP to the
      intranuclear ring zone in a similar pattern to full-length p74. The hydrophobic C
      terminus of p74 plays a role in protein localization and possibly in
      transmembrane anchoring and insertion.

PMID- 11514741
TI  - Expression and localization of LEF-11 in Autographa californica
      nucleopolyhedrovirus-infected Sf9 cells.
AB  - The Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV) lef-11 gene
      was found previously to be necessary to support optimal levels of transient
      expression from an AcMNPV late promoter. The lef-11 gene is unusual in that it
      overlaps both upstream (orf38) and downstream (pp31) genes. In this study, the
      expression and cellular localization of LEF-11 were examined. The lef-11
      transcripts were detected from 4 to 36 h post-infection (p.i.). The 1.5 kb lef-11
      mRNA initiates 196 nt upstream of the lef-11 translation initiation codon, within
      the upstream orf38 gene. This relatively long 5' upstream region encodes a
      potential small upstream open reading frame (ORF) of 58 amino acids that overlaps
      the lef-11 ORF. The 3' end of the lef-11 mRNA was mapped as co-terminal with
      mRNAs from the downstream pp31 gene. Using affinity purified anti-LEF-11
      antibodies, levels of LEF-11 expression were found to be maximal between
      approximately 8 and 24 h p.i., although LEF-11 could be detected as late as 72 h
      p.i. Using immunofluorescence microscopy, it was determined that LEF-11 localized
      to dense regions of infected cell nuclei, consistent with its role as a possible
      late transcription factor.

PMID- 11514742
TI  - Phylogenetic analysis of conserved genes within the ecdysteroid UDP
      glucosyltransferase gene region of the slow-killing Adoxophyes orana
      granulovirus.
AB  - A physical map of the genome of Adoxophyes orana granulovirus (AoGV) was
      constructed for the restriction enzymes BamHI, BglII, EcoRI, PstI and SacI using
      restriction endonuclease analysis and DNA hybridization techniques. This enabled
      the size of the AoGV genome to be estimated at 100.9 kbp. A plasmid library
      covering 99.9% of the AoGV genome was constructed using five restriction enzymes.
      The ecdysteroid UDP-glucosyltransferase gene (egt) was located by hybridization
      with the egt gene of Cydia pomonella granulovirus. The sequence of 6000 bp of the
      egt region is presented and compared to the equivalent area in other GVs.
      Database searches showed that this region contained eight open reading frames
      (ORFs) similar to the baculovirus genes egt, granulin, pk-1, me53 and four ORFs
      of Xestia c-nigrum granulovirus (ORF 178, ORF 2, ORF 7 and ORF 8). The egt gene
      was shown to encode an active EGT using an EGT assay. Phylogenetic trees of the
      granulovirus genes egt, granulin, pk-1 and me53 were constructed using maximum
      parsimony and distance analyses. These analyses indicated that AoGV genes may be
      more closely related to other tortricid-infecting GVs than to GVs that infect
      other lepidopteran families.

PMID- 11514743
TI  - Health care reform in Hong Kong.

PMID- 11514744
TI  - Epidemiology of acute primary angle-closure glaucoma in the Hong Kong Chinese
      population: prospective study.
AB  - OBJECTIVES: To determine the incidence of acute primary angle-closure glaucoma in
      the Hong Kong Chinese population, and to identify risk factors for this
      condition. DESIGN: Prospective study. SETTING: University teaching hospital, Hong
      Kong. PARTICIPANTS: Patients with acute primary angle-closure glaucoma presenting
      between 1 March 1998 and 29 February 2000. MAIN OUTCOME MEASURES: Demographic
      data, presenting symptoms and signs, temporal details of the presentation, and
      precipitating factors. The crude regional incidence was calculated according to
      the Hong Kong population census of 1991 and the age-specific incidence was
      calculated. RESULTS: Seventy-two cases (72 eyes of 72 patients) of acute primary
      angle-closure glaucoma were recruited. The crude incidence was 10.4 per 100,000
      per year in the population aged 30 years and older. Patients at higher risk of
      attacks were those aged 70 years or older (age-specific incidence, 58.7 per
      100,000 per year) and females, who had a relative risk of 3.8 compared with males
      (95% confidence interval, 1.7-8.4). Only four (5.6%) patients had a positive
      family history of acute primary angle-closure glaucoma. Seventeen (23.6%)
      patients were noted to have an upper respiratory tract infection before the
      attack, and 25 (34.7%) patients had taken antitussive agents. There was a
      statistically significant inverse correlation between the monthly attack rate and
      the monthly rate of influenza (Spearman's rank correlation coefficient = -0.388;
      P=0.031). CONCLUSION: There is a high incidence of acute primary angle-closure
      glaucoma among Chinese residents of Hong Kong, with elderly females at highest
      risk. A significant proportion of patients reported upper respiratory tract
      infection or the use of antitussive medication prior to attacks.

PMID- 11514745
TI  - Biliary tract disease and acute non-A-E hepatitis in Hong Kong: prospective
      study.
AB  - OBJECTIVE: To investigate the role of biliary tract disease in patients with
      acute non-A-E hepatitis. DESIGN: Prospective study. SETTING: Infectious diseases
      unit, government hospital, Hong Kong. PATIENTS: Sixty-one consecutive patients,
      admitted with the diagnosis of acute hepatitis and negative hepatitis serology
      for hepatitis A, B, C, D, and E virus. MAIN OUTCOME MEASURES: Abdominal
      ultrasound and endoscopic retrograde cholangiopancreatography findings; clinical
      outcome. RESULTS: Ultrasonographic abnormalities indicating biliary tract disease
      were found in 30% (18/61) of patients. Endoscopic retrograde
      cholangiopancreatography performed in 78% (14/18) of patients with abnormal
      ultrasound finding(s) confirmed the presence of biliary tract disease. Age, sex,
      serum alanine aminotransferase level, and serum albumin level were independent
      predictors of biliary tract disease in the patients studied. CONCLUSION: Biliary
      tract diseases were found in 20% of patients with acute non-A-E hepatitis. Serum
      amylase and abdominal ultrasonography should be performed for all patients
      presenting with acute non-A-E hepatitis. Endoscopic retrograde
      cholangiopancreatography is indicated for those with apparent gallstones or
      abnormal biliary tract findings.

PMID- 11514746
TI  - Morbidity patterns of non-urgent patients attending accident and emergency
      departments in Hong Kong: cross-sectional study.
AB  - OBJECTIVES: To study the morbidity patterns of non-urgent patients utilising
      accident and emergency services and compare these patients with 'true' accident
      and emergency cases. To analyse the morbidity pattern of non-urgent cases over
      different time periods, and across different age groups. DESIGN: A cross
      sectional study completed over a 1-year period. SETTING: Four accident and
      emergency departments in Hong Kong. PATIENTS: Two thousand, four hundred and ten
      patients randomly selected from four accident and emergency departments. MAIN
      OUTCOME MEASURES: The morbidity patterns by body system, according to the
      International Classification of Primary Care, were tabulated and analysed for
      'true' accident and emergency cases versus non-urgent cases. The ten most
      frequent diagnoses for the 'true' accident and emergency and non-urgent cases
      were also compared. Further analysis of accident and emergency service
      utilisation was conducted comparing different age groups, and also different time
      periods. RESULTS: Significantly more cases presenting to the accident and
      emergency service with respiratory and digestive problems were found to be non
      urgent, rather than appropriate accident and emergency cases. In contrast,
      significantly more cases presenting with circulatory and neurological problems
      were appropriate cases for accident and emergency department management. The
      morbidity pattern for the ten most frequent diagnoses seen in non-urgent cases
      was noted to be similar to the Hong Kong general practice morbidity pattern for
      self-limiting conditions. Utilisation of accident and emergency services for
      acute self-limiting conditions was more marked in the late evening, and also
      among children and the younger population in general. CONCLUSION: The utilisation
      of accident and emergency services by patients requiring a general practice
      service only, reflects problems in the primary health care delivery system. These
      may be solved by appropriate interfacing between general practitioners and other
      service providers, with the aim of providing seamless health care. Without
      revision of primary health care services, accident and emergency departments will
      continue to be used inappropriately by patients as an alternative to general
      practice care.

PMID- 11514747
TI  - Prognosis of acute pelvic fractures in elderly patients: retrospective study.
AB  - OBJECTIVE: To analyse the pattern of acute pelvic fractures, prognostic
      indicators, and intermediate-term functional outcome among elderly patients.
      DESIGN: Retrospective study. SETTING: Community-based hospital, Hong Kong.
      PATIENTS: Sixty patients older than 60 years who were admitted to hospital with
      acute pelvic fracture between 1 November 1993 and 31 December 1996. MAIN OUTCOME
      MEASURES: Review of medical records and X-ray assessment to determine the
      patients' demographic data, medical comorbidities, aetiology and mechanism of
      injury, associated injuries, and clinical outcome indicators such as
      complications, duration of hospital stay, ambulatory status, and 1- and 2-year
      mortality rates. RESULTS: The mean follow-up period was 29 months (range, 12 to
      65 months). Eighty-seven percent of patients were women and the predominant
      fracture pattern was Tile A2. The leading cause of injury was low-energy fall
      injury (75%). The 1-year mortality rate was nearly 12%. Thirty-six percent of
      patients experienced a decline in ambulatory status. Twenty-five percent of
      superior rami fractures involved the low anterior column of the acetabulum. There
      was a high incidence of associated cardiovascular disorders. CONCLUSIONS: Pre
      existing medical conditions and acetabular involvement are important adverse
      factors affecting postinjury ambulatory status. A significant decline in
      ambulatory status and a significant mortality rate at 1 year were found following
      pelvic fracture in elderly patients.

PMID- 11514748
TI  - Family doctors' attitudes towards patient self-management of upper respiratory
      tract infections.
AB  - OBJECTIVES: To determine the clinical attitudes and behaviour of family doctors
      in Hong Kong towards patient self-management of upper respiratory tract
      infections, and factors which may influence this practice. DESIGN: Questionnaire
      survey conducted between February 1999 and April 1999. SETTING: Hong Kong College
      of Family Physicians. PARTICIPANTS: Members of the Hong Kong College of Family
      Physicians. RESULTS: A total of 730 family doctors completed a postal
      questionnaire on self-management of upper respiratory tract infection, giving an
      overall response rate of 71.9%. The majority (95.2%) of respondents agreed that
      patients should be advised on self-management. More than two thirds (69.7%) of
      respondents also considered patients should be advised on self-medications for
      upper respiratory tract infection. Nearly two thirds and one third of respondents
      stated they would advise more than 60% of patients on self-management and self
      medication, respectively. A close association was noted between the doctor's view
      on the usefulness of antibiotics for upper respiratory tract infection and
      patient advice regarding self-management and self-medication strategies.
      CONCLUSION: Doctors with certain characteristics are more likely to advise
      patients with upper respiratory tract infection on self-management and self
      medication for upper respiratory tract infection.

PMID- 11514749
TI  - The reform of health care funding.
AB  - It is argued that the history of health care in Hong Kong has been characterised
      by the lack of a coherent government policy concerning who should provide, use,
      and pay for services. This has led to the present fragmented funding and delivery
      system. Past reforms have been piecemeal and have failed to address fundamental
      issues. The Harvard Report offered a comprehensive solution, but its insurance
      based approach to funding was politically unacceptable. Since funding determines
      patterns of service delivery, reform in that area is the necessary precondition
      for any substantive improvement in the quality and quantity of health care.
      Integrated funding mixes public and private money to overcome
      compartmentalisation between sectors. Without this, it is doubtful that a primary
      led health care system could operate. Whether Government has the political will
      to implement its current proposals in the face of opposition, and whether these
      will provide a sufficient foundation for the development of primary-led health
      care, remains to be seen.

PMID- 11514750
TI  - Health care funding and delivery in Hong Kong: what should be done?
AB  - This paper outlines a taxonomy of alternative health care funding avenues and the
      implications of these alternatives. The current approach to health care funding
      in Sweden is highlighted and a similar proposal outlined to meet the Hong Kong
      situation. The benefits of the proposed combination of tax-funded and capped
      voluntary payments, supplemented by 'moral hazard neutral' fees are presented, in
      terms of expenditure containment, universal access to health care, and optimal
      resource allocation.

PMID- 11514751
TI  - Realising the value of primary care.
AB  - The immediate task in primary care is to respond to patient demand. In the
      absence of other influences, the resulting system of care tends to be both
      inefficient and inequitable. Primary care has been shown to be increasingly
      capable of making important contributions to public health, however, by delaying
      or reducing the complications of established conditions, and by reversing risks
      in people who are otherwise well. Increasingly, quality of care depends on
      continuity of care with better communication and cooperation between all
      concerned. Whether such possibilities are realised depends on the nature and
      volume of publicly funded support for education and training in primary care, and
      the types of support given for decisions taken at many levels. Greater
      integration is needed within primary care to improve its internal effectiveness
      and efficiency, and as a basis for better integration with secondary care.
      Primary care needs to be cultivated rather than managed, because of the
      complexity and importance of clinical decision-making at this level, and because
      of variations in the needs of individual patients, and local populations.

PMID- 11514752
TI  - Efficiency is dependent on the control of supply.
AB  - At a time when health care systems are undergoing reform, it is useful to review
      the causes of inefficiency in health care, along with potential solutions. Such
      solutions can affect suppliers (supply-side measures) or users of care (demand
      side measures). This paper argues that to have an efficient health care system,
      supply-side measures must be implemented. Some examples of supply-side measures,
      with particular relevance to the Hong Kong situation, are discussed. By their
      nature, supply-side measures require government intervention. Only then, can
      allocative efficiency, as well as technical efficiency, be achieved. Once a
      health care system is operating efficiently, it is an easier task to determine
      whether the system requires more resources, either currently, or in the future.

PMID- 11514753
TI  - Ensuring the quality of health care.
AB  - The importance of high standards and striving for excellence in the Hong Kong
      health care system have been affirmed in the debate following release of the
      Harvard Report. This paper reviews the issue of quality in health care and
      recommends a triad quality framework to achieve this, consisting of enhancing
      professional practice, empowering patients, and providing a facilitative
      environment in which quality of care is encouraged.

PMID- 11514754
TI  - Invasive disease due to Mucorales: a case report and review of the literature.
AB  - OBJECTIVE: To review the mycology, pathogenesis, clinical characteristics,
      investigations, and treatment modalities of mucormycosis. DATA SOURCES: A local
      case of mucormycosis; MEDLINE and non-MEDLINE search of the literature. STUDY
      SELECTION: Key words for the literature search were 'mucormycosis' and
      'Mucorales'; all available years of study were reviewed. DATA EXTRACTION:
      Original articles, review papers, meta-analyses, and relevant book chapters were
      reviewed. DATA SYNTHESIS: Mucormycosis is a fungal infection that is rare but
      increasingly recognised in the growing population of immunocompromised patients.
      It is caused by saprophytic non-septate hyphae of the order Mucorales. The
      pulmonary and disseminated forms commonly occur in patients with haematological
      malignancy, especially acute leukaemia and lymphoma, and those receiving
      treatment with immunosuppressive effects. The rhinocerebral form is more
      prevalent in patients with diabetes mellitus, particularly those with the
      complication of diabetic ketoacidosis. The use of amphotericin B combined with
      surgery remains the mainstay of treatment. The prognosis largely depends on
      prompt correction of the underlying risk factors. New strategies to combat this
      life-threatening infection will result from better understanding of its
      pathogenesis. CONCLUSION: A high index of suspicion is needed, in appropriate
      clinical settings, to diagnose and aggressively treat this infection in view of
      the high mortality rate for susceptible patients.

PMID- 11514755
TI  - Endonasal endoscopic removal of growth-hormone-secreting pituitary adenomas.
AB  - Trans-sphenoidal removal of pituitary tumours using the endonasal endoscopic
      technique, a novel application, is herein reported in five consecutive patients
      with growth-hormone-secreting pituitary adenomas seen at a teaching hospital in
      Hong Kong. All five patients demonstrated complete tumour removal on
      postoperative imaging and hormonal assessment following the procedure. Surgical
      morbidity and symptoms were minimal; postoperative obstructive nasal packing was
      not required with this technique, which greatly improved patient comfort.
      Preliminary experience suggests that the endonasal endoscopic approach is a safe
      and effective alternative to the conventional trans-septal microscopic method for
      the treatment of pituitary tumour. A randomised controlled trial comparing these
      two approaches is currently underway at this institution.

PMID- 11514756
TI  - First fatal case of enterovirus 71 infection in Hong Kong.
AB  - Enteroviruses are a common cause of childhood infections, from hand, foot and
      mouth disease, to lethal brainstem encephalitis. Enterovirus 71 was first
      isolated in 1969. Brainstem encephalomyelitis and pulmonary oedema are postulated
      to be causally related and have been found to be a common feature of fatal
      enterovirus 71 cases. A fatal case of enterovirus 71 infection in a 2-year-old,
      previously healthy boy is reported. He presented to the Department of Paediatrics
      with clinical features of sepsis within 3 days of onset of fever. A few minutes
      after injection of midazolam, fentanyl and vecuronium for intubation, cardiac
      arrest developed and was not amenable to various treatment modalities. Pulmonary
      haemorrhage and oedema were noted during intubation, and postmortem examination
      confirmed the presence of brainstem encephalomyelitis.

PMID- 11514757
TI  - Porphyria cutanea tarda and melioidosis.
AB  - Porphyria cutanea tarda is a metabolic disorder in the haem biosynthetic pathway.
      It includes a heterogeneous group of conditions, which may be inherited or, more
      commonly, acquired. Although porphyria cutanea tarda presents with cutaneous
      lesions only, it is often associated with systemic disease. A 64-year-old Chinese
      patient, who developed sporadic porphyria cutanea tarda 1 year after the
      diagnosis of pulmonary melioidosis, is discussed. The patient presented with a
      history of recurrent photosensitive vesicles, blisters, and skin fragility on the
      sun-exposed areas of both forearms and hands, 6 months after commencing
      doxycycline and amoxycillin. Both the histological and biochemical findings were
      characteristic of porphyria cutanea tarda. All the lesions subsided after
      cessation of these antibiotics. The patient was free of further lesions at follow
      up 6 months later. The association seen in this case between porphyria cutanea
      tarda and melioidosis is unlikely to be coincidental, because these two diseases
      are both very rare in Hong Kong. In addition, the temporal relationship between
      the antibiotic therapy and the clinical course of skin lesions in this patient
      suggests that the drugs were a trigger factor, precipitating their appearance.

PMID- 11514758
TI  - A case of thoracic empyema due to suppurative melioidosis.
AB  - Melioidosis is considered a rare disease in Hong Kong, and its diagnosis and
      treatment can be difficult. We report the case of a patient who presented with
      thoracic empyema. The material sampled from the empyema was initially labelled
      Burkholderia cepacia. The diagnosis of melioidosis due to Burkholderia
      pseudomallei could only be made after repeated cultures, and performing arginine
      dihydrolase and serological tests. The patient was initially treated with
      imipenem for 2 weeks, and then with ciprofloxacin as maintenance therapy. A
      resistant strain of the organism developed after 7 months of treatment. The
      patient was then given co-amoxiclav. Repeated courses of surgical drainage and
      debridement were also instituted. Subsequent computed tomographic scanning of the
      thorax showed gradual resolution of the empyema.

PMID- 11514759
TI  - Primary human immunodeficiency virus infection: heightened awareness needed.
AB  - Primary human immunodeficiency virus infection is a distinct medical syndrome
      which is often not diagnosed. The importance of its early recognition lies in the
      potential for early therapeutic intervention for the individual, with consequent
      public health benefits for the community at large. Diagnosis requires a high
      index of suspicion in a person with a history of potential exposure. Early
      treatment with combination antiretroviral therapy should be considered once the
      diagnosis has been established. We report a local case of primary human
      immunodeficiency virus infection in a patient who presented initially with fever,
      lymphadenopathy, generalised skin rash, dry cough, splenomegaly, and aseptic
      meningitis.

PMID- 11514760
TI  - A young male patient with persistent fever due to tuberculous peritonitis.
AB  - Tuberculous peritonitis is an uncommon disease in Hong Kong. We report a case of
      tuberculous peritonitis in a young male. The patient presented with persistent
      fever and intermittent cough for 1 month, but had no gastrointestinal symptoms.
      It was only through detection of slight abdominal ascites that subsequent
      abdominal paracentesis and laparoscopic biopsy confirmed the diagnosis.
      Appropriate antituberculous treatment was prescribed. Progress was complicated by
      persistent fever and liver function derangement, successfully managed by careful
      titration of antituberculous medications.

PMID- 11514761
TI  - Hypothyroidism and simvastatin.

PMID- 11514764
TI  - Intertrochanteric osteotomy for posttraumatic arthritis after acetabular
      fractures.
AB  - OBJECTIVE: To evaluate the long-term results of intertrochanteric osteotomies for
      posttraumatic arthritis after acetabular fractures. DESIGN: Retrospective study
      of eight patients who underwent a total of ten intertrochanteric osteotomies. Two
      patients underwent two osteotomies of the same hip. SETTING: Academic Level I
      trauma center. PARTICIPANTS: Patients who developed posttraumatic hip arthritis
      after nonoperatively or operatively treated acetabulum fractures. The average age
      of patients was twenty-nine years (range 16 to 47 years). INTERVENTION: Patients
      underwent an intertrochanteric osteotomy to decrease contact pressures on damaged
      cartilage and to lessen contractures. All intertrochanteric osteotomies at our
      institution were performed by the senior author (R.K.M.). MAIN OUTCOME
      MEASUREMENTS: The Merle d'Aubigne score and the Thompson and Epstein score were
      determined based on each patient's last follow-up. RESULTS: At an average long
      term follow-up of 10.2 years (range 2.5 to 22 years), all eight patients had a
      significant improvement based on the Merle d'Aubigne score (average increase 5.3
      points). Less improvement was observed according to the Thompson and Epstein
      score, which is consistent with the fact that radiographic appearance is weighted
      disproportionally in that score. CONCLUSIONS: Because most acetabular fracture
      patients are relatively young, the option of joint replacement for posttraumatic
      hip arthritis is less than ideal. However, we have observed significant
      improvement in hip function with a decrease in pain and disability when such
      patients are treated with an intertochanteric osteotomy.

PMID- 11514765
TI  - Prospective randomized controlled trial of an intramedullary nail versus dynamic
      screw and plate for intertrochanteric fractures of the femur.
AB  - OBJECTIVES: To compare the surgical complications and functional outcome of the
      Gamma nail intramedullary fixation device versus the Richards sliding hip screw
      and plate device in intertrochanteric femoral fractures. DESIGN: A prospective,
      randomised controlled clinical trial with observer blinding. SETTING: A regional
      teaching hospital in the United Kingdom. PATIENTS: All patients admitted from the
      local population with intertrochanteric fractured femurs were included. There
      were 400 patients entered into the study and 399 followed-up to one year or
      death. INTERVENTION: The devices were assigned by randomization to either a short
      type Gamma nail (203 patients) or a Richard's-type sliding hip screw and plate
      (197 patients). MAIN OUTCOME MEASUREMENTS: The main surgical outcome measurements
      were fixation failure and reoperation. A functional outcome of pain, mobility
      status, and range of movement were assessed until one year. RESULTS: The
      requirement for revision in the Gamma nail group was twelve (6%); for Richard's
      group, eight (4%). This was not statistically different (p = 0.29; odds ratio,
      1.48 [0.59-3.7]). A subcapital femoral fracture occurred in the Richard's group.
      Femoral shaft fractures occurred with four in the Gamma nail group (2%) and none
      in the Richard's group (p = 0.13). Three required revision to another implant.
      Lag-screw cut-out occurred in eight patients in the gamma nail group (4%) and
      four in the Richard's group (2%). This was not statistically significant (p =
      0.37; odds ratio, 2.29 [0.6-9.0]). The development of other postoperative
      complications was the same in both groups. There was no difference between the
      two groups in terms of early or long-term functional status at one year.
      CONCLUSIONS: The use of an intramedullary device in the treatment of
      intertrochanteric femoral fractures is still associated with a higher but
      nonsignificant risk of postoperative complications. Routine use of the Gamma nail
      in this type of fracture cannot be recommended over the current standard
      treatment of dynamic hip screw and plate.

PMID- 11514766
TI  - Prospective randomized comparison between a dynamic hip screw and a mini-invasive
      static nail in fractures of the trochanteric area: preliminary results.
AB  - OBJECTIVES: This study aimed at comparing the results obtained with a sliding
      screw plate and an experimental device including a small-diameter nail that can
      be placed with a mini-invasive approach and provides a stable fixation. DESIGN:
      Randomized prospective study. SETTING: University hospital. PATIENTS: The study
      included two groups with thirty fractures of the trochanteric area.
      INTERVENTIONS: In both groups, the surgical procedure was carried out on patients
      placed on a traction table in a supine position, under an x-ray amplifier.
      Sliding screw plates (THS) were set in place according to the usual open
      technique. Nails were placed through a twenty-millimeter supratrochanteric
      cutaneous incision. This experimental system comprised a locked intramedullary
      nail with two nonparallel seven-millimeter cervicocephalic screws. MAIN OUTCOME
      MEASURES: The comparison between the two groups was based on the surgical
      procedure (time, duration of x-ray irradiation, and total blood loss); the
      initial postoperative period (complications, duration of hospital stay, and the
      time before returning home); the time before full weight bearing became
      effective; the functional and social recovery; mortality; and the quality of
      immediate and final anatomic restitution and healing. RESULTS: Operating time (p
      < 0.001) and blood loss (p < 0.001) were lower in the nail group, and no blood
      transfusion was required. Postoperative pain (p < 0.01), time necessary to
      support full weight bearing (p < 0.02), and time before returning home (p < 0.05)
      were reduced in the nail group. All fractures healed in the same amount of time,
      with good anatomic results in the nail group, whereas ten impactions beyond ten
      millimeters occurred in the plate group. No difference was found between the two
      groups in walking ability and autonomy recovery, but hip function (p < 0.05) was
      better in the nail group. CONCLUSION: This preliminary clinical study has shown
      the advantages of this mini-invasive technique. It could not evaluate all the
      possible disadvantages inherent in the method. These points will be evaluated in
      a multicenter study justified by these preliminary results.

PMID- 11514767
TI  - Radiographic results of callus distraction aided by pulsed low-intensity
      ultrasound.
AB  - OBJECTIVES: To determine whether pulsed low-intensity ultrasound (frequency of
      1.5 megahertz, pulsed by one kilohertz, signal burst width of 200 microseconds,
      intensity of thirty milliwatts per square centimeter, and daily treatment time of
      twenty minutes per day) stimulates regenerate maturation after callus
      distraction. DESIGN: Prospective, controlled animal trial. METHODS: Operatively,
      we created a fifteen-millimeter defect in the right metatarsus of eighteen female
      mature merino sheep. A segmental transport was begun on Day 5 using a high
      stiffness experimental ring fixator. The distraction rate was one millimeter per
      day divided into two increments of 0.5 millimeters each. On Day 21 after the
      operation, distraction was finished and the maturation period started and lasted
      until Day 84 after operation. During this period, Group 1 was treated with a
      daily twenty-minute low-intensity ultrasound stimulation (frequency of 1.5
      megahertz, pulsed by one kilohertz, signal burst width of 200 microseconds,
      intensity of thirty milliwatts per square centimeter). Group 2 had no
      stimulation. Animals bore full weight. Plain radiographs in the anteroposterior
      view were taken every two weeks during the maturation period. After the animals
      were killed on Day 84, anteroposterior and lateral high resolution radiographs
      and computed tomography (CT) scans of the regenerate were performed. For each
      plain and high resolution radiograph, two different relationships (callus
      relation, the ratio of the amount of periosteal callus to the size of the space
      between the proximal fragment and transported segment; and interzone relation,
      the ratio of the fibrous callus interzone to the size of the new formed callus)
      were calculated. Using CT scan, callus area, bone density, and bone mineral
      content were evaluated. RESULTS: The results of interzone relation (both views)
      and callus relation (lateral view) in high-resolution radiographs and bone
      mineral content in CT indicate a significantly accelerated maturation of the
      regenerate in the ultrasound stimulated group even when a Bonferroni-Holm
      adjustment was used for multiple testing. CONCLUSION: Pulsed low-intensity
      ultrasound appears to stimulate the healing processes in the regenerate in this
      animal model and may have applicability in clinical practice.

PMID- 11514768
TI  - Rates and odds ratios for complications in closed and open tibial fractures
      treated with unreamed, small diameter tibial nails: a multicenter analysis of 467
      cases.
AB  - OBJECTIVE: A multicenter trial analyzed complications and odds for complications
      in open and closed tibial fractures stabilized by small diameter nails. DESIGN:
      Retrospective. SETTING: Four Level I trauma centers. PATIENTS: Four hundred sixty
      seven tibial fractures were included in the study. There were fifty-two proximal
      fractures, 219 midshaft fractures, and 196 distal fractures. Breakdown into
      different AO/OTA groups showed 135 Type A fractures, 216 Type B fractures, and
      116 Type C fractures. Two hundred sixty-five were closed fractures and 202 were
      open fractures. OUTCOME MEASUREMENTS: Clinical and radiographic analysis.
      METHODS: 467 patients' tibial fractures were stabilized with small diameter
      tibial nails using an unreamed technique. Indications for the use of small
      diameter tibial nails using an unreamed technique included all types of open or
      closed diaphyseal fractures. The operating surgeons decided whether or not to
      ream based on personal experience, fracture type, and soft-tissue damage.
      Surgeons of Center 1 preferred to treat AO Type A and B fractures with unreamed
      nails, and surgeons of Centers 2, 3, and 4 preferred to treat AO Type B and C
      fractures with unreamed nails. Closed and open fractures were treated in
      approximately the same ratio. RESULTS: Analysis showed five (1.1 percent) deep
      infections (with a 5.4 percent rate of deep infections in Gustilo Grade III open
      fractures), forty-three delayed unions (9.2 percent), and twelve (2.6 percent)
      nonunions. Compartment syndromes occurred in sixty-two cases (13.3 percent),
      screw fatigue in forty-seven cases (10 percent), and fatigue failure of the
      tibial nail in three cases (0.6 percent). CONCLUSIONS: Fracture distraction of
      more than three millimeters should not be tolerated when stabilizing tibial
      fractures with unreamed, small-diameter nails as this increases the odds of
      having a delayed union by twelve times (p < 0.001) and a nonunion by four times
      (p = 0.057). There was a significant increase of complications in the group of
      Grade III open fractures (p < 0.001), AO/OTA Type C fractures (p = 0.002), and to
      a lesser extent in distal fractures. However, the rate of severe complications
      resulting in major morbidity was low.

PMID- 11514769
TI  - In vitro elution of tobramycin from bioabsorbable polycaprolactone beads.
AB  - OBJECTIVES: To compare the in vitro elution characteristics of tobramycin
      impregnated beads made of polycaprolactone (PCL) and polymethylmethacrylate
      (PMMA). DESIGN: Six-millimeter PCL and PMMA beads with 6% tobramycin were formed
      and placed in phosphate-buffered saline or newborn calf serum and incubated at
      room temperature or 37 degrees C. Aliquots were taken at intervals for eight
      weeks. Tobramycin levels were determined by fluorescent assay and antibacterial
      efficacy was assessed by measuring the zones of inhibition against Staphylococcus
      aureus and Pseudomonas aeruginosa on agar diffusion plates. RESULTS: Tobramycin
      elution rates at room temperature were similar up to three weeks. At three weeks,
      elution rates from PCL beads were twice those from PMMA beads, and at eight
      weeks, elution from PCL was quadruple that from PMMA. At 37 degrees C, tobramycin
      elution rates from PCL were eight times greater than those from PMMA by eight
      weeks. Total tobramycin eluted from PCL beads was 38.9% and 20% in PMMA beads.
      All samples showed bacteriostatic activity against S. aureus and P. aeruginosa at
      eight weeks. CONCLUSIONS: These in vitro results show that PCL has superior
      antibiotic elution characteristics compared with PMMA, and this may translate
      into a more effective antibiotic delivery vehicle. In addition, PCL is a
      bioabsorbable polymer, which may decrease the need for a second surgical
      procedure to remove retained beads.

PMID- 11514770
TI  - Pullout strengths of self-reinforced poly-L-lactide (SR-PLLA) rods versus
      Kirschner wires in bovine femur.
AB  - OBJECTIVE: To determine the relative amount of fixation of self-reinforced poly-L
      lactide (SR-PLLA) rods and Kirschner wires in bovine cancellous bone by comparing
      their pullout strength DESIGN: An in vitro laboratory study was performed using
      bovine femurs. Ten two-millimeter-diameter pins of each type were inserted into
      cancellous bone and then pulled out, using a material testing machine. The
      maximum force (pullout strength) was selected over other measurements to compare
      the amount of fixation of the two types of pins. All of the pins were retrieved
      for microscopic analysis. A paired t test was performed to analyze the
      differences between the pullout strength of the two types of pins. SETTING:
      Orthopaedic Bioengineering Laboratory, University of Louisville School of
      Medicine, Louisville, Kentucky, U.S.A. SPECIMENS: Two young fresh bovine distal
      femurs, ten two-millimeter-diameter Kirschner wires, ten two-millimeter-diameter
      bioabsorbable SR-PLLA rods MAIN OUTCOME MEASUREMENTS: Pullout strength in
      Newtons, and microscopic pin surface aspect after insertion. RESULTS: Significant
      differences were noted between the maximum force required to remove the two types
      of pins (p < 0.01) The K-wire mean pullout force was 37.7 N (SD 13.6), and the SR
      PLLA rod mean pullout force was 53.6 N (SD 19.3). Microscopic analysis indicated
      surface modification only on the SR PLLA rods. DISCUSSION: SR-PLLA composites
      have shown comparable clinical results to their metallic counterparts. In this
      study, the pullout strength of SR-PLLA rods was compared with that of
      conventional K-wires. A significant difference (p < 0.01) favoring bioabsorbable
      pullout strength was noted. The bioabsorbable pin surface modification during
      insertion is an interesting finding that warrants further investigation as a
      potential source of improved fixation. CONCLUSION: SR-PLLA rods retain their hold
      in bovine cancellous bone better than K-wires. This finding offers to the
      orthopaedic surgeon more information about new pin fixation methods.

PMID- 11514771
TI  - Potential of increased risk of neurovascular injury using proximal interlocking
      screws of retrograde femoral nails in patients with acetabular fractures.
AB  - OBJECTIVES: Neurologic and vascular structures are at risk of iatrogenic injury
      from proximal interlocking screw insertion after retrograde nailing. This risk
      may increase in the presence of acetabular fractures because of the displacement
      of soft tissues resulting from hematoma. The purpose of this study was to
      establish and compare the relative safe zones (RSZs) for interlocking screw
      insertion in adults with and without concomitant acetabular fractures. MATERIALS
      AND METHODS: Thirty pelvic computed tomography scans of patients with acute
      unilateral acetabular fracture and magnetic resonance imaging scans of five
      healthy legs were used to evaluate the course of the femoral sheath,
      neurovascular complex, and the sciatic nerve as they course through the proximal
      thigh in sixty-five limbs. RESULTS: The anatomy of the neurovascular structures
      on the fractured side was statistically different from that of the normal side.
      On the normal side, the RSZ at the lesser trochanteric level was identified from
      +7 degrees medial to +20 degrees lateral to the sagittal axis (27-degree angle
      zone) for anteroposterior screw placement. These values for the fractured side,
      respectively, changed to +1 degrees and +14 degrees (13-degree angle zone), a 52
      percent decrease. The RSZ for lateral-medial screw placement was 28 degrees
      anterior to 39 degrees posterior to the coronal axis (67-degree angle zone) for
      the normal side, which changed, respectively, to 32 degrees and 41 degrees (73
      degree angle zone) for the fractured side. At the level of the lesser trochanter,
      rotation in the femoral shaft was mimicked only in part (approximately 50
      percent) by the neurovascular structures. CONCLUSION: Lateral-medial screw
      insertion is safer than anteroposterior insertion. Anteroposterior screw
      insertion becomes even more critical if the acetabulum is fractured. Femoral
      external rotation after rod insertion, but before screw insertion, will enlarge
      the safe zones.

PMID- 11514772
TI  - Dermatotraction: an effective technique for the closure of fasciotomy wounds: a
      preliminary report of fifteen patients.
AB  - Dermatotraction was evaluated as an alternative technique for the closure of
      dermatofasciotomy wounds, with a review of literature and of our clinical
      experience. The dermatotraction technique provides closure of fasciotomy wounds
      and avoids the use of skin grafting. Patients treated with dermatofasciotomy for
      an acute compartment syndrome of the limbs, without obvious tissue necrosis and
      without shock or urgent life saving surgery, had their fasciotomy wound closed
      with dermatotraction with vessel loops, the skin approximation system, or the
      prepositioned intracutaneous suture. In our experience, the mean time to wound
      closure was nine days. Dermatotraction techniques that cause local skin
      compression should be avoided because skin necrosis might occur (skin
      approximation system). Dermatotraction with vessel loops or the prepositioned
      intracutaneous suture provides good skin apposition without the necessity for
      skin grafting.

PMID- 11514773
TI  - Paradoxical fat embolism after intramedullary rodding: a case report.
AB  - Following intramedullary rodding of two long-bone fractures, a twenty-year-old
      woman developed the clinical picture of fat embolism syndrome with severe
      neurological involvement. Corroborating evidence suggested paradoxical
      embolization of fat as the precipitating cause of this neurologic deterioration.
      The suspected pathophysiology of this event is discussed.

PMID- 11514774
TI  - Bowel herniation after traumatic symphysis pubis diastasis.
AB  - The authors describe a patient with small bowel herniation after traumatic
      symphysis disruption. Although gastrointestinal problems occur rarely with pelvic
      fractures, in a patient with a pubic diastasis and paralytic ileus, the
      development of abdominal hernia through torn peritoneum should be considered.
      Treatment of the patient with a pubic diastasis and a bowel problem should
      include early careful exploration and management of the gastrointestinal tract
      during pelvic surgery.

PMID- 11514775
TI  - Marginal plafond impaction in association with supination-adduction ankle
      fractures: a report of eight cases.
AB  - In five years, approximately 800 ankle fractures were seen at the authors'
      institution, forty-four (5 percent) of which were of the supination-adduction
      pattern. Nineteen of these injuries had displaced vertical medial malleolus
      fractures, of which eight (42 percent) showed marginal impaction of the tibial
      plafond. All eight patients underwent open reduction and internal fixation with
      elevation of the impacted articular component and had good to excellent
      functional outcome with no arthritis on radiograph at the time of the most recent
      follow-up. The index of suspicion of marginal impaction of the tibial plafond
      should be high when treating supination-adduction pattern ankle fractures with
      displaced medial malleolus.

PMID- 11514776
TI  - Ulnar bursa distention following volar subluxation of the distal radioulnar joint
      after distal radial fracture: a rare cause of carpal tunnel syndrome.
AB  - This report describes an eighty-four-year-old woman with persistent carpal tunnel
      syndrome attributable to an ulnar bursa distention associated with the
      subluxation of the distal radioulnar joint after distal radial fracture. During
      surgery, when the forearm was placed in supination, the ulna head with a sharp
      osteophyte was found to be displaced into the carpal tunnel through a defect of
      the ruptured capsule of the wrist joint. This volar subluxation of the ulnar head
      had caused distention of the ulnar bursa, causing compression of the median
      nerve, which resulted in carpal tunnel syndrome. In addition to reduce displaced
      fractured segment to obtain anatomic articular surface, original radial length
      and tilt, the anatomic restoration of the distal radioulnar joint is essential to
      maintain better long-term function after fracture of the distal radius.

PMID- 11514777
TI  - Intraarticular distal radius fracture.

PMID- 11514778
TI  - Statistical correctness.

PMID- 11514779
TI  - Statistical correctness.

PMID- 11514782
TI  - Are you pro-evidence?

PMID- 11514783
TI  - Prospective randomized study of reamed versus unreamed femoral intramedullary
      nailing: an assessment of procedures.

PMID- 11514784
TI  - Diagnosis and management of superficial bladder cancer.
AB  - Bladder cancer is the fourth leading cause of cancer in American men, accounting
      for more than 12,000 deaths annually. It was one of the first malignancies in
      which carcinogens were recognized as an important factor in its cause. Currently,
      cigarette smoking is by far the most common cause of bladder cancer, although
      occupational exposure to arylamines has been implicated in the past. Gross or
      microscopic hematuria is the most common sign at presentation. Initial radiologic
      evaluation usually includes the excretory urography (intravenous pyelography),
      although further evaluation of the renal parenchyma with ultrasound or computed
      tomography scanning has been advocated by some. These radiologic studies are
      unable to provide adequate bladder imaging, and thus cystoscopy is required for
      the diagnosis of bladder cancer. Most bladder cancers present as "superficial"
      disease, confined to the bladder mucosa or submucosal layer, without muscle
      invasion. Superficial tumors consist of papillary tumors that are mucosally
      confined (Ta), papillary or sessile tumors extending into the lamina propria
      (T1), and carcinoma in situ, which occurs as "flat" mucosal dysplasia, which can
      be focal, diffuse, or associated with a papillary or sessile tumor. The natural
      history of these pathologic subtypes differ significantly. Most superficial
      tumors (60% to 70%) have a propensity for recurrence after transurethral
      resection. Some (15% to 25%) are at high risk for progression to muscle invasion.
      Most superficial tumors can be stratified into high- or low-risk groups depending
      on tumor stage, grade, size, number, and recurrence pattern. It is important to
      identify those tumors at risk for recurrence or progression so that adjuvant
      intravesical therapies can be instituted. Many intravesical chemotherapeutic
      agents have been shown to reduce tumor recurrence when used in conjunction with
      transurethral tumor resection. Unfortunately, however, none of these agents have
      proved to be of benefit in preventing disease progression. Most are given
      intravesically on a weekly basis, although many studies suggest that a single
      instillation immediately after transurethral resection may be as good as a longer
      course of therapy. Although all of these drugs have toxicity, they usually are
      well tolerated. Intravesical bacille Calmette-Guerin (BCG) is an
      immunotherapeutic agent that when given intravesically is very effective in the
      treatment of superficial transitional cell carcinoma. Compared with controls, BCG
      has a 43% advantage in preventing tumor recurrence, a significantly better rate
      than the 16% to 21% advantage of intravesical chemotherapy. In addition, BCG is
      particularly effective in the treatment of carcinoma in situ, eradicating it in
      more than 80% of cases. In contrast to intravesical chemotherapy, BCG has also
      been shown to decrease the risk of tumor progression. The optimal course of BCG
      appears to be a 6-week course of weekly instillations, followed by a 3-week
      course at 3 months in those tumors that do not respond. In high-risk cancers,
      maintenance BCG administered for 3 weeks every 6 months may be optimal in
      limiting recurrence and preventing progression. Unfortunately, adverse effects
      associated with this prolonged therapy may limit its widespread applicability. In
      those patients at high risk in whom BCG therapy fails, intravesical interferon
      alpha with or without BCG may be beneficial in some. Photodynamic therapy has
      also been used but is limited by its toxicity. In patients who progress or do not
      respond to intravesical therapies, cystectomy should be considered. With the
      development of orthotopic lower urinary tract reconstruction to the native
      urethra, the quality of life impact of radical cystectomy has been lessened.

PMID- 11514785
TI  - Health promotion-fact or fiction?

PMID- 11514787
TI  - Service-learning, the scholarship of service.

PMID- 11514788
TI  - Barriers to tobacco cessation in clinical practice: report from a National Survey
      of Oncology Nurses.
AB  - This study describes the survey results of a national random sample of members of
      the Oncology Nursing Society who reported the greatest number of barriers to
      delivering a tobacco cessation intervention with their patients. Nurses who
      perceived the greatest number of barriers were more likely to be current smokers
      and to be young and were less likely to have an advanced degree, to be a nurse
      practitioner, or to have administrative responsibilities. Those with greater
      barriers were less likely to deliver tobacco cessation interventions.

PMID- 11514789
TI  - White paper on the health status of Asian Americans and Pacific Islanders and
      recommendations for research.
AB  - A literature review of various reports sponsored by federal governmental agencies
      and proceedings of conferences of Asian Americans' and Pacific Islanders' health
      organizations provides data of health disparities among and between these diverse
      ethnic groups. Specifically, demographic and socio-economic data, as well as
      health care issues, are reported. Asian Americans and Pacific Islanders exceed
      other groups in health disparities in the area of tuberculosis and hepatitis B,
      whereas cancer and cardiovascular diseases are leading causes of death within the
      Asian American and Pacific Islander populations. Recommendations for areas of
      research are provided.

PMID- 11514790
TI  - Increasing nursing postdoctoral opportunities: National Institute of Nursing
      Research Spring Science Work Group.
AB  - On May 1-2, 2000, the National Institute of Nursing Research (NINR) hosted a
      Spring Science Work Group on Increasing Nursing Postdoctoral Opportunities. The
      work group met at the National Institutes of Health (NIH) in Bethesda and was
      chaired by Dr Patricia A. Grady, director, and Dr Hilary D. Sigmon, program
      director, NINR. The purpose of the meeting was to identify ways to increase
      postdoctoral opportunities for nurse researchers. The work group considered the
      gaps and strengths currently present in postdoctoral education and suggested
      strategies and collaborative approaches for future initiatives. As biomedicine
      and behavioral science enter the 21st century, nurse scientists have critical
      roles to play in basic laboratory studies, translational research, clinical
      investigations, care delivery, and outcome evaluations. To fulfill these roles
      and to meet the growing need for well-trained nurse scientists in complex,
      multidisciplinary research, the "pipeline" of postdoctoral nurse researchers must
      be strengthened.

PMID- 11514791
TI  - Profound change: 21st century nursing.

PMID- 11514792
TI  - Building health services research capacity in nursing: views from members of
      nursing's leadership [interview by Candice Cook Bowman and Deborah Gardner].
AB  - BACKGROUND: Despite a short history that dates back to the 1960s, health services
      research (HSR) has become an important force in shaping the delivery system in
      the current health care environment. Nursing has been noticeably absent from this
      endeavor, and if it does not increase its presence, it risks missing an important
      opportunity to influence future directions of health care delivery. PURPOSE: Our
      purpose was to evaluate the state of nursing's HSR contributions and to consider
      ways to increase its capacity in this arena. METHOD: An interview with four
      members from nursing's leadership was conducted. DISCUSSION: Nurses can increase
      the capacity by becoming better collaborators with those who are currently
      contributing to HSR, both nurses and members of other healthcare disciplines.
      Also, by reshaping undergraduate and graduate curricula and creating mentorships,
      nursing can increase its involvement through an informed workforce. CONCLUSIONS:
      Solutions that were offered in this discussion are presented.

PMID- 11514793
TI  - Balancing freedom with risks: the experience of nursing task delegation in
      community-based residential care settings.
AB  - BACKGROUND: In 1995, Washington State implemented law reforming the state's long
      term care system, favoring provision of service in less restrictive, lower-cost
      settings. PURPOSE: The purpose was to systematically evaluate one facet of the
      new law regarding the implementation of a policy authorizing delegation of
      designated nursing tasks by registered nurses in community-based residential care
      settings. METHOD: This was a descriptive study driven by the inductive process of
      grounded theory. Qualitative data sources included interviews, public forums,
      document review, and open-ended survey questions to facility operators, nurses,
      nursing assistants, and inspectors. DISCUSSION: The study identified an
      overarching social process, balancing freedom with risks involving tension at the
      intersections, which is evident from 3 main perspectives: consumer, professional,
      and the health care system. CONCLUSIONS: The study has implications for
      regulatory consistency, nursing practice and education, collaboration between
      overlapping providers of skilled nursing services in residential settings, and
      subsequent health policy.

PMID- 11514794
TI  - President's message: global collegiality and collaboration.

PMID- 11514795
TI  - Some clinical factors related to rate of resorption of residual ridges. 1962.

PMID- 11514796
TI  - Implant repositioning for esthetic reasons: a clinical report.
AB  - This article describes the correction of an unesthetic implant position that
      resulted from unexpected postpubertal growth. Surgical implant repositioning, a
      technique similar to single-tooth osteotomies, was used. The implant and
      surrounding bone were mobilized, and a green stick fracture was made on the
      buccal plate. With pivoting on the buccal plate, the implant was moved to a more
      palatal position and restored. Although some degree of asymmetry could still be
      detected, a satisfactory esthetic result was achieved.

PMID- 11514797
TI  - An interim extraoral prosthesis used for the rehabilitation of a patient treated
      for osteoradionecrosis of the mandible: a clinical report.
AB  - In patients with tumors of the head and neck, ionizing radiation delivered in
      dosages that will kill cancer cells induces unavoidable changes in normal tissue.
      Bone cells and vascularity may be irreversibly injured, leaving devitalized bone
      susceptible to the development of osteoradionecrosis. This clinical report
      describes the fabrication of an acrylic/rubber prosthesis retained by an
      orthodontic headgear. The prosthesis was used to improve the mastication, speech,
      and saliva control of a patient treated for osteoradionecrosis of the mandible.

PMID- 11514798
TI  - Use of a silicone disclosing material in patients with embrasure undercuts.

PMID- 11514799
TI  - Magnets in prosthetic dentistry.
AB  - Magnetic retention is a popular method of attaching removable prostheses to
      either retained roots or osseointegrated implants. This review chronicles the
      development of magnets in dentistry and summarizes future research in their use.
      The literature was researched by using the Science Citation Index and Compendex
      Web from 1981 to 2000. Articles published before 1981 were hand researched from
      citations in other publications. Articles that discussed the use of magnets in
      relation to prosthetic dentistry were selected.

PMID- 11514800
TI  - Repair of denture base resins with visible light-polymerized reline material:
      effect on tensile and shear bond strengths.
AB  - STATEMENT OF PROBLEM: Triad visible light-polymerized (VLP) reline resin has the
      potential to repair denture bases from other resin systems with the elimination
      of flasking/deflasking procedures. PURPOSE: This study measured the tensile and
      shear bond strengths of Triad VLP, PMMA, and glass-fiber-reinforced PMMA (GF
      PMMA) acrylic resins before and after repair with Triad VLP reline material.
      MATERIAL AND METHODS: Fifty-six specimens were fabricated from Triad VLP, PMMA,
      and GF-PMMA denture base resins. Both Triad VLP reline material and
      autopolymerizing acrylic resins were used to repair identical laboratory
      fabricated resin joints. Twenty-eight rectangular specimens (in 4 different
      groups of 7 each) were prepared to study the shear bond strength of Triad reline
      material used to repair different denture base resin joints. RESULTS:
      Statistically significant differences (P< .0001) were found between the tensile
      strengths of specimens repaired with the Triad VLP reline resin used as a repair
      agent and those repaired with the autopolymerizing resin. The tensile strength of
      the Triad VLP denture base resin was found to be higher than that of both the
      PMMA and GF-PMMA acrylic resins. CONCLUSION: The low tensile and shear bond
      strengths found after the repair of PMMA and GF-PMMA acrylic resins with Triad
      VLP reline material were attributed to a lack of cohesion/adhesion between the
      Triad VLP reline material and the interfaces of the treated sites. The use of
      Triad VLP reline material to repair Triad VLP denture base resin produced the
      highest strengths.

PMID- 11514801
TI  - In vitro fatigue resistance of glass ionomer cements used in post-and-core
      applications.
AB  - STATEMENT OF PROBLEM: New glass ionomer cements exhibit better mechanical
      properties than their older counterparts. However, there is concern about their
      use as a core material in post-and-core applications. PURPOSE: This in vitro
      study evaluated the fatigue resistance of 2 new glass ionomer cements, Shofu Hi
      Dense and Fuji IX GP, and compared their mechanical behavior as a core material
      under masticatory load with a silver-reinforced glass ionomer (ESPE Ketac-Silver)
      and a silver amalgam (Cavex Avaloy LC). MATERIAL AND METHODS: A total of 100
      commercial plastic teeth were divided into 4 groups of 25 specimens each.
      Titanium posts were placed in the prepared root canals, and cores were built up
      in amalgam, silver-reinforced glass ionomer cement, and the 2 new glass ionomer
      cements. The post-and-core specimens were prepared for full cast metal crowns,
      which were fabricated and cemented with glass ionomer cement. Twenty specimens
      from each group were placed in a mastication simulator and cyclically loaded with
      a 400 N force for 1.5 million cycles. The 5 remaining specimens were used as
      controls. The specimens were sectioned and observed macroscopically and
      microscopically to determine the number of defects (alterations) in each
      material. Observed defects were verified with the Kruskal-Wallis test, and the 4
      core materials were ranked with the Tukey multiple comparisons test. RESULTS: The
      mean rank sum values of the defects were as follows: Cavex Avaloy LC Amalgam
      (16.75), Fuji IX GP (38.50), Shofu Hi-Dense (39.53), and ESPE Ketac-Silver
      (67.22). The amalgam alloy was significantly different (P< .05) from the others.
      CONCLUSION: Under the conditions of this study, the 2 new glass ionomer cements
      used as core materials showed a higher number of defects than amalgam. These
      results suggest that their fatigue resistance may be inadequate for post-and-core
      applications.

PMID- 11514802
TI  - Fluoride release from restorative materials and a luting cement.
AB  - STATEMENT OF PROBLEM: In addition to conventional glass ionomers, a considerable
      number of different types of materials have been formulated to release fluoride.
      Variation in composition results in quantitative differences in the amount of
      fluoride release by these materials. PURPOSE: This study evaluated and compared
      fluoride release in distilled water from different types of restorative materials
      and a luting cement. MATERIAL AND METHODS: Fluoride release from 4 glass ionomer
      formulation restorative materials (Miracle-Mix, Fuji ionomer type III, Fuji II LC
      improved, and Ketac-Silver), a luting cement (Ketac Cem), a compomer (Compoglass
      Flow), 2 sealants (Fissurit F, Helioseal F), and a composite resin (Tetric) was
      evaluated at time intervals of 4, 8, 12, and 24 hours and 2, 3, 7, 14, 28, 56,
      and 112 days. Seven disks of each material were made and stored for equilibration
      in double distilled water at 37 degrees C for the time of each measurement. The
      equilibrated solution was analyzed for fluoride with a TISAB and an ion-specific
      combination electrode (ORION 960900) connected to an expandable ion analyzer
      (Crison micropH 2002). Data were analyzed by means of univariate analysis of
      variance, the Dunnett C post hoc test, and repeated measures analysis. RESULTS:
      Fluoride was released from all the evaluated materials, with considerable
      variation in the rate of release but a similar pattern. Among the materials
      tested, fluoride release from glass ionomer formulations was greater than that
      from composite resin formulations; the rank of decreasing order was as follows:
      Miracle Mix > Fuji III, Ketac Cem > Fuji II LC > Ketac Silver, Compoglass F >
      Fissurit F, Helioseal F > Tetric (> indicates statistical significance; P< .05).
      CONCLUSION: Under the conditions of this study, glass ionomer formulations and
      the compomer released more fluoride than the sealants and the composite resin
      tested.

PMID- 11514803
TI  - The effect of disinfection and a wetting agent on the wettability of addition
      polymerized silicone impression materials.
AB  - STATEMENT OF PROBLEM: The wettability of silicone impression materials is poor,
      which may lead to voids within casts. All impression materials should be
      disinfected before use, but disinfection may affect their wettability. PURPOSE:
      This study evaluated the effect of disinfection procedures and the use of a
      surface wetting agent on the wettability of 4 addition-polymerized silicone
      impression materials. MATERIAL AND METHODS: Testing specimens were made from 4
      addition silicone materials (light-bodied President, light-bodied Extrude, medium
      bodied Extrude, and Aquasil). Two disinfection solutions (Actichlor and Perform)
      and 1 wetting agent (Vacufilm) were used. The test conditions were as follows:
      (A) dry, (B) Vacufilm, (C) Actichlor (10-minute soak), (D) Actichlor (10-minute
      soak) and Vacufilm, (E) Perform (10 minute-soak), and (F) Perform (10-minute
      soak) and Vacufilm. A dynamic contact angle analyzer was used to measure the
      wettability of specimens. Mean results were compared with 1-way ANOVA, and
      multiple comparisons were made with the Bonferroni method. RESULTS: Treatments C,
      D, and F had no significant effect on the wettability of the materials. Treatment
      B significantly reduced the contact angle for light-bodied President (P< .01) and
      Aquasil (P< .05). Treatment E significantly increased the contact angle for light
      and medium-bodied Extrude and Aquasil (P< .001). CONCLUSION: Disinfection with
      Actichlor is recommended in preference to Perform to maintain the wettability of
      impression materials. Treatment with Vacufilm after disinfection is recommended
      to improve the wettability of materials and thus reduce the likelihood of voids
      within casts.

PMID- 11514804
TI  - Type and incidence of cracks in posterior teeth.
AB  - STATEMENT OF PROBLEM: The use of magnified vision in the operatory has enhanced
      the early diagnosis of structural defects in the dentition and in existing
      restorations. There is little in the literature to guide the clinician on the
      significance of cracks and other interruptions in the integrity of teeth.
      PURPOSE: This study characterized the type and incidence of cracks in posterior
      teeth and identified possible etiologic factors. MATERIAL AND METHODS: An
      observational cross-sectional survey of 51 patients from a private practice
      examined during an 18-month period was used to identify 4 types of cracks in
      posterior teeth. The study identified both patient- and tooth-level variables
      present in each patient examined. The data were subjected to statistical analysis
      to determine whether correlations existed between the variables and cracks.
      RESULTS: Cracks in teeth were shown to have chronicity and can be classified
      according to appearance. Variables such as the presence of a Class I or II
      restoration and the presence of excursive interferences were shown to
      significantly increase (P< .0001) the chances of a crack being present.
      Combinations of variables, such as interferences and a restoration, also
      increased the chance of a crack being present. CONCLUSION: Within the limitations
      of this study, the presence of cracks in teeth was associated with the placement
      of a Class I or II restoration and with the presence of excursive interferences.
      Age played a role in the presence of stained or symptomatic cracks, which
      suggests that cracks have chronicity. Although many questions remain regarding
      prevention, it is evident that protecting teeth from excursive interferences and
      parafunction may thwart premature breakdown.

PMID- 11514805
TI  - Communicating facial plane information to the dental laboratory: introducing the
      Facial Plane Relator device.
AB  - The ability of the restorative dentist to communicate the location and
      orientation of the patient's pertinent facial landmarks to the dental laboratory
      technician has great bearing on the esthetic success of final anterior dental
      restorations. This article describes a new device designed to facilitate this
      process.

PMID- 11514806
TI  - Immediate provisional restorations to aid in gingival healing and optimal
      contours for implant patients.
AB  - A procedure for making an impression at stage I implant surgery is described, and
      the sequential laboratory procedures for fabricating a custom provisional
      restoration are presented. The provisional restoration is delivered at the
      uncovering of the implant, providing a template for the tissue healing with
      desired contours. This procedure facilitates the fabrication of implant
      restorations with optimal gingival contours and esthetics.

PMID- 11514807
TI  - Alternative method for retention and removal of cement-retained implant
      prostheses.
AB  - This article describes a simple, quick, and economical technique that makes use
      of a light-polymerized resin system to facilitate the retention and removal of
      cement-retained implant prostheses.

PMID- 11514808
TI  - A review of temporomandibular disorder diagnostic techniques.
AB  - The American Dental Association has approved several devices as aids in the
      diagnosis of temporomandibular disorders. Concerns remain, however, about their
      safety and effectiveness. This article reviews the validity and use of several
      instruments that claim to serve as aids in the detection of masticatory muscle
      pain, trismus, joint noises, and limitation of jaw motion. A review of data from
      62 published articles indicated that, although commercial devices that measure
      jaw muscle tenderness, muscle activity levels, joint noises, and jaw motion are
      safe and can document these phenomena, cost-benefit analyses of these devices
      have not yet been conducted. Moreover, these devices have not been shown to have
      stand-alone diagnostic value and, when tested, they have demonstrated
      unacceptable sensitivity and specificity levels. None of the instruments reviewed
      in this article can be said to provide more than ancillary documentation.

PMID- 11514809
TI  - A piezoelectric film-based intrasplint detection method for bruxism.
AB  - STATEMENT OF PROBLEM: An accurate, easy-to-use, long-term method other than EMG
      is needed to monitor bruxism. PURPOSE: This article presents pilot data on the
      reproducibility, validity, and utility of an intrasplint piezoelectric film
      method. MATERIAL AND METHODS: Simulated bruxism behaviors (steady-state and
      rhythmic clenching, grinding, and tapping) in 5 subjects were recorded with the
      use of both masseter EMG and an intrasplint piezoelectric film method. RESULTS:
      Correlation coefficients calculated for simulated bruxism event duration with the
      use of a masseter EMG or an intrasplint piezoelectric film method were 0.99 for
      tapping and steady-state clenching, 0.96 for rhythmic clenching, and 0.79 for
      grinding. CONCLUSION: Piezoelectric film has its limitations and does not
      faithfully capture sustained force magnitudes. However, for the target behaviors
      associated with bruxism (tooth grinding, clenching, and tapping), it appears to
      faithfully reproduce above-baseline events with durations statistically
      indistinguishable from those recorded with masseter EMG. Masseter EMG was poorest
      at detecting a simulated side-to-side grinding behavior.

PMID- 11514810
TI  - Principles of biocompatibility for dental practitioners.
AB  - This article is an evidence-based tutorial on the principles of biocompatibility.
      Although the technical issues of biocompatibility may seem beyond the scope of
      most practicing dentists, knowledge of these issues is fundamentally important to
      ensure the health of patients, dental staff members (including laboratory
      personnel), and practitioners themselves. Furthermore, the legal liability of
      dentists is often linked to biocompatibility issues. The biocompatibility of a
      material is not absolute; it must be measured with regard to the way the material
      is used. Measuring biocompatibility is a complex process that involves in vitro
      and in vivo tests. These tests contribute to understanding biologic responses to
      a material but cannot define the material's biocompatibility with 100% certainty.
      Practitioners should understand enough about biocompatibility testing methods to
      critically judge advertising claims and ask relevant questions of manufacturers.
      Because there is no infallible way to assess biologic response to a material,
      decisions about the clinical use of a material ultimately must weigh the biologic
      risks of a material against its potential benefits.

PMID- 11514811
TI  - Technique for fabricating a lightweight, urethane-lined silicone orbital
      prosthesis.
AB  - A technique is presented for packing an acrylic resin core and controlling the
      thickness of an orbital prosthesis with the use of an irreversible hydrocolloid
      matrix. This technique provides a durable core without damaging the orbital
      prosthesis mold and permits a controllable thickness and therefore a lighter
      prosthesis.

PMID- 11514812
TI  - Simple method for making a metal crown for a complete denture.

PMID- 11514813
TI  - Chronic pediatric asthma and chiropractic spinal manipulation: a prospective
      clinical series and randomized clinical pilot study.
AB  - OBJECTIVES: The first objective was to determine if chiropractic spinal
      manipulative therapy (SMT) in addition to optimal medical management resulted in
      clinically important changes in asthma-related outcomes in children. The second
      objective was to assess the feasibility of conducting a full-scale, randomized
      clinical trial in terms of recruitment, evaluation, treatment, and ability to
      deliver a sham SMT procedure. STUDY DESIGN: Prospective clinical case series
      combined with an observer-blinded, pilot randomized clinical trial with a 1-year
      follow-up period. SETTING: Primary contact, college outpatient clinic, and a
      pediatric hospital. PATIENTS: A total of 36 patients aged 6 to 17 years with mild
      and moderate persistent asthma were admitted to the study. OUTCOME MEASURES:
      Pulmonary function tests; patient- and parent- or guardian-rated asthma-specific
      quality of life, asthma severity, and improvement; am and pm peak expiratory flow
      rates; and diary-based day and nighttime symptoms. INTERVENTIONS: Twenty
      chiropractic treatment sessions were scheduled during the 3-month intervention
      phase. Patients were randomly assigned to receive either active SMT or sham SMT
      in addition to their standardized ongoing medical management. RESULTS: It is
      possible to blind the participants to the nature of the SMT intervention, and a
      full-scale trial with the described design is feasible to conduct. At the end of
      the 12-week intervention phase, objective lung function tests and patient-rated
      day and nighttime symptoms based on diary recordings showed little or no change.
      Of the patient-rated measures, a reduction of approximately 20% in beta(2)
      bronchodilator use was seen (P =.10). The quality of life scores improved by 10%
      to 28% (P <.01), with the activity scale showing the most change. Asthma severity
      ratings showed a reduction of 39% (P <.001), and there was an overall improvement
      rating corresponding to 50% to 75%. The pulmonologist-rated improvement was
      small. Similarly, the improvements in parent- or guardian-rated outcomes were
      mostly small and not statistically significant. The changes in patient-rated
      severity and the improvement rating remained unchanged at 12-month posttreatment
      follow-up as assessed by a brief postal questionnaire. CONCLUSION: After 3 months
      of combining chiropractic SMT with optimal medical management for pediatric
      asthma, the children rated their quality of life substantially higher and their
      asthma severity substantially lower. These improvements were maintained at the 1
      year follow-up assessment. There were no important changes in lung function or
      hyperresponsiveness at any time. The observed improvements are unlikely as a
      result of the specific effects of chiropractic SMT alone, but other aspects of
      the clinical encounter that should not be dismissed readily. Further research is
      needed to assess which components of the chiropractic encounter are responsible
      for important improvements in patient-oriented outcomes so that they may be
      incorporated into the care of all patients with asthma.

PMID- 11514814
TI  - Reducing the personal risk of perceived disease: the chiropractic patients' self
      care endeavor.
AB  - OBJECTIVE: It has been suggested that clinicians should be looking at new ways to
      enhance the self-care of their patients. Patient education is one strategy that
      primary providers may use. This study investigates the behavior of chiropractic
      patients to identify whether they are using widely published community health
      information messages to reduce their personally perceived risk of various
      diseases. METHODS: An exploratory study of chiropractic patients was undertaken
      to investigate the health-relevant behaviors of patients. Purposive sampling of 9
      Australian chiropractic clinics was undertaken. Convenience sampling of patients
      attending these clinics resulted in the participation of 102 patients. All
      participants completed a questionnaire, and data were collected and collated into
      a series of case studies that described some behaviors of participants that might
      have influenced their risk of acquiring disease. The study was limited to
      diseases for which participants believed they were at risk. RESULTS: A
      substantial number of participants had undergone a screening procedure as
      recommended by health authorities. The 67 participants who believed they were at
      risk for one or more of the conditions listed were more likely to have complied.
      In addition, all participants made certain healthy lifestyle choices. However,
      implementation of those lifestyle choices that would reduce the personal risk of
      perceived diseases was sporadic. CONCLUSION: The behavior of participants in this
      study suggests that many chiropractic patients would benefit from additional
      personalized health information messages. The use of information brochures in
      chiropractic clinics may not alone lead to a lifestyle change.

PMID- 11514815
TI  - Effect of chiropractic intervention on small scoliotic curves in younger
      subjects: a time-series cohort design.
AB  - BACKGROUND: Chiropractors have long claimed to affect scoliotic curves, and case
      studies abound reporting on successful outcomes. No clinical trials exist,
      however, that evaluate chiropractic's effectiveness in the management of
      scoliotic curves. OBJECTIVE: To assess the effectiveness of chiropractic
      intervention in the management of adolescent idiopathic scoliosis in curves less
      than 20 degrees. DESIGN: Cohort time-series trial with all subjects electing
      chiropractic care. Entry-level Cobb angle was compared with postmanagement curve.
      METHODS: Forty-two subjects completed the program of chiropractic intervention.
      Age range at entry was 6 to 12 years, and patients were included if their entry
      level x-ray films revealed curves of 6 degrees to 20 degrees. Participants had
      adjustments performed for 1 year before follow-up. Full-spine osseous adjustments
      were the major form of intervention, but heel lifts and postural and lifestyle
      counseling were used as well. RESULTS: There was no discernable effect on the
      severity of the curves as a function of age, initial curve severity, frequency of
      care, or attending physician. CONCLUSION: Full-spine chiropractic adjustments
      with heel lifts and postural and lifestyle counseling are not effective in
      reducing the severity of scoliotic curves.

PMID- 11514816
TI  - Effectiveness of spinal manipulative therapy in the treatment of mechanical
      thoracic spine pain: a pilot randomized clinical trial.
AB  - BACKGROUND: To date, no substantiated studies have been performed to investigate
      the efficacy of spinal manipulative therapy on thoracic spinal syndromes.
      OBJECTIVE: To investigate the effectiveness of spinal manipulative therapy in the
      treatment of mechanical thoracic spine pain. STUDY DESIGN: A single-blind,
      randomized, comparative, controlled pilot study. SETTING: Technikon Natal
      Chiropractic Clinic in Durban, South Africa. PARTICIPANTS: Thirty subjects
      selected from the general population (from 16 to 60 years old) were randomly
      divided into two different treatment groups of 15 each. METHODS: The objective
      measurements collected were the thoracic spine ranges of motion with the BROM II
      goniometer and pain threshold with an algometer. The subjective information
      required completion of the Oswestry Back Pain Disability Index, short-form McGill
      Pain Questionnaire, and Numerical Pain Rating Scale-101 Questionnaire by the
      patient. These 3 forms and objective measurements were collected before the first
      and final treatment and again at the 1-month follow-up consultation. The data
      gathered were then statistically analyzed with use of a 95% confidence level. The
      nonparametric Mann-Whitney U test and the Wilcoxon signed-rank test were used to
      compare intergroup and intragroup data, respectively. This was conducted at the
      alpha =.05 level of confidence. Further assessment of the data was conducted by
      use of power analysis. INTERVENTIONS: The treatment group received thoracic
      spinal manipulation. The placebo group received nonfunctional ultrasound
      application only. The research project was carried out so that both groups
      received 6 treatments over a period of 2 to 3 weeks. A 1-month follow-up
      appointment was scheduled after the final treatment to assess the relative long
      term benefits of the two different treatments. RESULTS: Statistically significant
      results (P < or = .025) were noted for the percentage of pain experienced
      (Numerical Pain Rating Scale) and for right and left lateral flexion during
      intergroup comparison after the final treatment. The final treatment results were
      maintained at the 1-month follow-up consultation; however, there were no further
      statistically significant results. It was noted that the power was weak, so the
      probability of committing type II error (falsely accepting the null hypothesis)
      for the other measurements was high. The intragroup analysis showed statistically
      significant improvements in the group that received spinal manipulative therapy
      in both subjective and objective measurements between the first to final
      treatment and the first treatment to the 1-month follow-up consultation. The
      placebo group analysis showed a statistically significant improvement in sensory
      pain only (subjective measurement) between the first treatment and the final
      treatment. CONCLUSIONS: This pilot study suggests that spinal manipulative
      therapy has greater benefits than placebo treatment. The sample size was small,
      therefore the findings of this trial study should not be considered conclusive
      but rather should be used as a foundation for planning future studies. In further
      studies a larger sample size will be necessary to identify subtle changes in
      measurement parameters and to add to the validity of the results.

PMID- 11514817
TI  - Effects of a mechanical pain stimulus on erector spinae activity before and after
      a spinal manipulation in patients with back pain: a preliminary investigation.
AB  - BACKGROUND: Several recent studies in animal models of spinal pain have shown
      changes in sensory processing and in reflex muscular responses. One group of
      researchers reported consistent electromyographic responses in the paraspinal
      muscles of healthy men after spinal manipulation, and they speculated that such
      responses may underlie some of the observed clinical effects of spinal
      manipulation (namely, reduction in pain and muscular hypertonicity). OBJECTIVES:
      To determine whether a painful mechanical stimulus applied above a spinous
      process influences paraspinal electromyographic amplitude and whether this
      response is modulated by a spinal manipulation. STUDY DESIGN: Analytic cohort
      with a convenience sample in a research clinic. METHODS: Seventeen subjects with
      back pain (9 men and 8 women) were recruited. Electromyographic signals were
      recorded from the paraspinal musculature during the following procedures before
      and after manipulation: quiet stance and prone during the application of a
      mechanical pain stimulus. A 2-way repeated-measures analysis of variance was used
      to compare the effect of the force application on electromyographic amplitude. A
      second 2-way repeated-measures analysis of variance investigated whether the
      muscular response to a painful stimulus at either segment was influenced by the
      manipulative procedure. RESULTS: A statistically significant increase in
      bilateral electromyographic activity was observed at the painful motion segment;
      however, no such statistical increase occurred at the segment that was not
      painful. It appears that manipulation results in a decrease in bilateral local
      electromyographic activity in the painful motion segment during the application
      of the mechanical stimulus; however, a statistically significant decrease was not
      found in the control segment. It was also found that while the subjects were
      quietly standing, the left erector spinae at a painful segment was the only
      muscle group to show significant differences before and after manipulation.
      CONCLUSION: This study suggests that motion segments identified as a problem in
      subjects with chronic low back pain have an exaggerated local muscular response
      to a painful stimulus compared with that observed in problem segments. In
      addition, spinal manipulation appears to attenuate the electromyographic response
      to a painful stimulus.

PMID- 11514818
TI  - Chiropractic technique procedures for specific low back conditions:
      characterizing the literature.
AB  - BACKGROUND: Many original clinical trials and several review papers have come to
      the conclusion that manipulation is safe and effective for the treatment of low
      back pain. However, it is necessary to determine which specific types of
      manipulation and nonmanipulative types of chiropractic adjustive care are most
      effective for particular types of low back pain across both tissue-specific and
      functional classifications. OBJECTIVE: To characterize the quantity and quality
      of literature gathered for an Expert Panel that was convened to rate various
      specific chiropractic adjustive procedures for the treatment of common types of
      low back pain, drawing on the clinical expertise of the panel members and the
      relevant literature. STUDY DESIGN: Systematic review of treatment-specific,
      condition-specific trials, studies, and case reports of chiropractic care for low
      back pain. METHODS: Computerized searching and hand searching were used to
      identify references in the medical and chiropractic literature pertaining to the
      chiropractic treatment of low back pain in which both the condition and specific
      treatment procedures were adequately described. This literature was then
      categorized according to a variety of characteristics and used by a panel to
      evaluate the specific procedures. RESULTS: The 3 most studied adjustive
      procedures are side-posture high-velocity, low-amplitude; distraction (mostly
      flexion distraction); and mobilization, respectively. The clinical condition most
      commonly addressed by the included studies is low back pain. The procedure with
      the widest base of evidence support is side posture manipulation for low back
      pain.

PMID- 11514820
TI  - The chiropractor's role in pain management for oncology patients.

PMID- 11514819
TI  - Chiropractic management of a professional hockey player with recurrent shoulder
      instability.
AB  - OBJECTIVE: To describe the clinical management of recurrent shoulder instability
      in a professional hockey player by using chiropractic management and
      rehabilitation exercises. CLINICAL FEATURES: A 23-year-old professional hockey
      player with recurrent left shoulder pain and instability. He had two previous
      unsuccessful shoulder operations to correct the instability. He reported that the
      shoulder "slips out" in positions of abduction and external rotation or when the
      left arm is moved suddenly above shoulder height. The patient was still playing
      hockey professionally at the time of the initial visit and did not want to have
      to take time off for another surgery, so he chose to attempt a conservative
      approach. INTERVENTION AND OUTCOME: The patient had undergone strength training
      for rehabilitation after each of the previous two shoulder operations and had
      very strong rotator cuff and scapular musculature. Proprioceptive testing
      revealed a poor response in the left shoulder compared with the right shoulder.
      Two subjective outcome measures were used to determine the effectiveness of the
      treatment protocol in reducing the symptoms of recurrent shoulder instability.
      Much of the treatment focused on proprioceptive training, soft tissue
      mobilization, and improving joint function. CONCLUSION: This case demonstrates
      the potential benefit of chiropractic management and proprioceptive exercises to
      decrease the symptoms of recurrent shoulder instability.

PMID- 11514821
TI  - Cellular transplantation for the treatment of heart failure. State of the art.

PMID- 11514822
TI  - Cytokines and troponin-I in cardiac dysfunction after coronary artery grafting
      with cardiopulmonary bypass.
AB  - OBJECTIVE: The association between cytokines and troponin-I with cardiac function
      after cardiac surgery with cardiopulmonary bypass remains a topic of continued
      investigation. METHODS: Serial measurements, within 24h following surgery, of
      tumor necrosis factor-alpha, its soluble receptors, and troponin-I were performed
      in patients with normal ejection fraction undergoing coronary artery bypass
      grafting. Ejection fraction was measured by radioisotopic ventriculography
      preoperatively, at 24h and at day 7 postoperatively. RESULTS: Of 19 patients
      studied (59+/-8.5 years), 10 (group 1) showed no changes in ejection fraction,
      53+/-8% to 55+/-7%, and 9 (group 2) had a decrease in ejection fraction, 60+/-11%
      to 47+/-11% (p=0.015) before and 24h after coronary artery bypass grafting,
      respectively. All immunological variables, except tumor necrosis factor-alpha
      soluble receptor I at 3h postoperation (5.5+/- 0.5 in group 1 versus 5.9+/-0.2
      pg/ml in group 2; p=0.048), were similar between groups. Postoperative troponin-I
      had an inverse correlation with ejection fraction at 24h (r= -0.44). CONCLUSIONS:
      Inflammatory activity, assessed based on tumor necrosis factor-alpha and its
      receptors, appears to play a minor role in cardiac dysfunction after cardiac
      surgery. Troponin I levels are inversely associated with early postoperative
      ejection fraction.

PMID- 11514823
TI  - Percutaneous mechanical mitral commissurotomy performed with a Cribier's metallic
      valvulotome. Initial results.
AB  - OBJECTIVE: To evaluate the immediate results of percutaneous mechanical mitral
      commissurotomy. METHODS: Thirty patients underwent percutaneous mechanical mitral
      commissurotomy performed with a Cribier's metallic valvulotome from 8/11/99 to
      2/4/00. Mean age was 30.7 years, and 73.3% were women. With regards to functional
      class, 63.3% were class III, and 36.7% were class IV. The echocardiographic score
      had a mean value of 7.5+/- 1.8. RESULTS: The mitral valve area increased from
      0.97+/-0.15cm2 to 2.16+/-0.50cm2 (p>0.0001). The mean diastolic gradient
      decreased from 17.9+/-5.0mmHg to 3.2+/-1.4mmHg. The mean left atrial pressure
      decreased from 23.6+/-5.4mmHg to 8.6+/-3.1mmHg, (p>0.0001). Systolic pressure in
      the pulmonary artery decreased from 52.7+/-18.3mmHg to 32.2+/-7.4mmHg. Twenty
      nine cases were successful. One patient developed severe mitral regurgitation.
      Interatrial septal defect was observed and one patient. One patient had cardiac
      tamponade due to left ventricular perforation. No deaths occurred. CONCLUSION:
      This method has proven to be safe and efficient in the treatment of rheumatic
      mitral stenosis. The potential advantage is that it can be used multiple times
      after sterilization, which decreases procedural costs significantly.

PMID- 11514825
TI  - Application of receptive music therapy in internal medicine and cardiology.
AB  - OBJECTIVE: To investigate the effects of receptive music therapy in clinical
      practice. METHODS: Receptive music therapy was individually applied via musical
      auditions, including five stages: musical stimulation, sensation, situation,
      reflection, and behavioral alteration. Following anamnesis and obtainment of
      consent, patients answered a first questionnaire on health risk evaluation (Q1),
      and after participating in 16 weekly music therapy sessions, answered a second
      one (Q2). RESULTS: Two men and 8 women, aged above 18 years, referred to us due
      to symptoms of stress, emotional suffering, and the need to change lifestyles
      (health risk behavior) were studied between August 1998 and December 1999.
      Comparison between answers to Q1 and Q2, showed a trend (P=0.059) for reduction
      of ingestion of cholesterol-rich foods and for increased prospects in life with a
      tendency towards improvement, and also of increased intake of fiber-rich food
      (55.6%), increased levels of personal satisfaction (44.5%), and decreased levels
      of stress (66.7%). CONCLUSION: The study demonstrated decreased stress levels and
      increased personal satisfaction, higher consumption of fiber-rich food, lower
      cholesterol intake, and a better perspective on life, suggesting that receptive
      music therapy may be applied in clinical practice as an auxiliary therapeutic
      intervention for the treatment of behavioral health risks.

PMID- 11514824
TI  - Reduction in diastolic blood pressure and cardiovascular mortality in nondiabetic
      hypertensive patients. A reanalysis of the HOT study.
AB  - OBJECTIVE: To use published Hypertension Optimal Treatment (HOT) Study data to
      evaluate changes in cardiovascular mortality in nondiabetic hypertensive patients
      according to the degree of reduction in their diastolic blood pressure. METHODS:
      In the HOT Study, 18,700 patients from various centers were allocated at random
      to groups having different objectives of for diastolic blood pressure: </=90
      (n=6264); </=85 (n=6264); </=80mmHg (n=6262). Felodipine was the basic drug used.
      Other antihypertensive drugs were administered in a sequential manner, aiming at
      the objectives of diastolic blood pressure reduction. RESULTS: The group of
      nondiabetic hypertensive subjects with diastolic pressure</=80mmHg had a
      cardiovascular mortality ratio of 4.1/1000 patients/year, 35.5% higher than the
      group with diastolic pressure </=90mmHg (cardiovascular mortality ratio, 3.1/1000
      patients/year). In contrast, diabetic patients allocated to the diastolic
      pressure objective group of </=80mmHg had a 66.7% reduction in cardiovascular
      mortality (3.7/1000 patients/year) when compared with the diastolic pressure
      group of </=90mmHg (cardiovascular mortality ratio, 11.1/1000 patients/year).
      CONCLUSION: The results indicate that in hypertensive diabetic patients reduction
      in diastolic blood pressure to levels </=80mmHg decreases the risk of fatal
      cardiovascular events. It remains necessary to define the level of diastolic
      blood pressure </=90mmHg at which maximal reduction in cardiovascular mortality
      is obtained for nondiabetics.

PMID- 11514826
TI  - Prognostic factors of the results of cardiopulmonary resuscitation in a
      cardiology hospital.
AB  - OBJECTIVE: To analyze the early and late results of cardiopulmonary resuscitation
      in a cardiology hospital and to try to detect prognostic determinants of both
      short- and long-term survival. METHODS: A series of 557 patients who suffered
      cardiorespiratory arrest (CRA) at the Dante Pazzanese Cardiology Institute over a
      period of 5 years was analyzed to examine factors predicting successful
      resuscitation and long-term survival. RESULTS: Ressuscitation maneuvers were
      tried in 536 patients; 281 patients (52.4%) died immediately, and 164 patients
      (30.6%) survived for than 24 hours. The 87 patients who survived for more than 1
      month after CRA were compared with nonsurvivors. Coronary disease,
      cardiomyopathy, and valvular disease had a better prognosis. Primary arrhythmia
      occurred in 73.5% of the >1-month survivor group and heart failure occurred in
      12.6% of this group. In those patients in whom the initial mechanism of CRA was
      ventricular fibrillation, 33.3% survived for more than 1 month, but of those with
      ventricular asystole only 4.3% survived. None of the 10 patients with
      electromechanical dissociation survived. There was worse prognosis in patients
      included in the extreme age groups (zero to 10 years and 70 years or more). The
      best results occurred when the cardiac arrest took place in the catheterization
      laboratories. The worst results occurred in the intensive care unit and the
      hemodialysis room. CONCLUSION: The results in our series may serve as a helpful
      guide to physicians with the difficult task of deciding when not to resuscitate
      or when to stop resuscitation efforts.

PMID- 11514827
TI  - [Multiple recurrences of cardiac myxomas with acute tumoral pulmonary embolism].
AB  - We report the case of a 42-year-old female with a second recurrence of cardiac
      myxoma. Her first diagnosis was at the age of 24 years, when cardiac tumors were
      withdrawn from her right ventricle and left atrium. Her first recurrence was at
      the age of 36 years, when tumors were removed from the left and right atria, and
      the right ventricle. Six years later, the patient was admitted to the Hospital
      das Clinicas de Porto Alegre complaining of sudden dyspnea, dry cough, and pain
      in the right hypochondrium, which bore no relation to breathing. The
      transesophageal echocardiography showed a small tumor in the interatrial septum,
      close to the superior vena cava, and 2 larger tumors in the right ventricle, 1
      close to the outflow tract and the other almost completely obstructing the right
      branch of the pulmonary artery. The patient was referred to surgery, in which
      myxomas were removed from the right atrium and ventricle with extension to the
      right pulmonary artery. The postoperative period was uneventful.

PMID- 11514828
TI  - A sixty-four-year-old woman with Chagas' disease, who underwent implantation of a
      permanent cardiac pacemaker and evolved with rapidly progressive heart failure.

PMID- 11514829
TI  - [Clinic radiological correlation - Case 8/2001 - Instituto do Coracao do Hospital
      das Clinicas da FMUSP].

PMID- 11514830
TI  - Pharmacological and clinical evidence for the use of low-molecular-weight
      heparins in acute coronary syndromes.

PMID- 11514831
TI  - [Cardiopulmonary resuscitation].

PMID- 11514833
TI  - Partial characterization of nif genes from the bacterium Azospirillum amazonense.
AB  - Azospirillum amazonense revealed genomic organization patterns of the nitrogen
      fixation genes similar to those of the distantly related species A. brasilense.
      Our work suggests that A. brasilense nifHDK, nifENX, fixABC operons and nifA and
      glnB genes may be structurally homologous to the counterpart genes of A.
      amazonense. This is the first analysis revealing homology between A. brasilense
      nif genes and the A. amazonense genome. Sequence analysis of PCR amplification
      products revealed similarities between the amino acid sequences of the highly
      conserved nifD and glnB genes of A. amazonense and related genes of A. brasilense
      and other bacteria. However, the A. amazonense non-coding regions (the upstream
      activator sequence region and the region between the nifH and nifD genes)
      differed from related regions of A. brasilense even in nitrogenase structural
      genes which are highly conserved among diazotrophic bacteria. The feasibility of
      the 16S ribosomal RNA gene-based PCR system for specific detection of A.
      amazonense was shown. Our results indicate that the PCR primers for 16S rDNA
      defined in this article are highly specific to A. amazonense and can distinguish
      this species from A. brasilense.

PMID- 11514832
TI  - Irinotecan and oxaliplatin: an overview of the novel chemotherapeutic options for
      the treatment of advanced colorectal cancer.
AB  - Colorectal cancer is one of the most frequent malignancies in humans and an
      important cause of cancer death. Metastatic colorectal cancer remains incurable
      with available systemic therapeutic options. The most active cytotoxic drug
      against this malignancy, the antimetabolite 5-fluorouracil, was developed more
      than forty years ago, and as a single agent produces responses in only 10 to 15%
      of patients which in general last less than one year. Efforts to ameliorate these
      poor results resulted in the 5-fluorouracil/leucovorin combination, which
      enhances response rates about two-fold, without, however, significantly improving
      survival rates. The recent emergence of a handful of new 5-fluorouracil analogues
      and folate antagonists, as well as the topoisomerase I inhibitor irinotecan, and
      the third-generation platinum compound oxaliplatin, is likely to alter this
      gloomy scenario. These agents are at least as effective as 5-fluorouracil in
      patients with advanced colorectal carcinoma, both untreated and previously
      treated with 5-fluorouracil-based regimens. This has led to the approval of
      irinotecan as second-line treatment for 5-fluorouracil-refractory disease, while
      the use of oxaliplatin has been suggested for patients having a defective 5
      fluorouracil catabolism. Recently, FDA approved the combination of irinotecan
      with 5-fluorouracil and leucovorin for first-line treatment of advanced colon
      cancer. Based on the synergistic preclinical antitumor effects of some of these
      agents, their meaningful single-agent activity, distinct mechanisms of
      cytotoxicity and resistance, and only partially overlapping toxicity profiles,
      effective combination regimens are now being developed, which are likely to lead
      to a new, more hopeful era for patients suffering from advanced colorectal
      carcinoma.

PMID- 11514834
TI  - A biolistic process for in vitro gene transfer into chicken embryos.
AB  - Chicken embryos kept in culture medium were bombarded using a high helium gas
      pressure biolistic device. To optimize the factors that affect transformation
      efficiency, the lacZ gene under control of the human cytomegalovirus immediate
      early enhancer/promoter was used as a reporter gene. There was an inverse
      relationship between survival rate and transformation efficiency. The best
      conditions obtained for high embryo survival and high transformation efficiency
      were achieved with 800 psi helium gas pressure, 500 mmHg vacuum, gold particles,
      an 8 cm DNA-coated microparticle flying distance to the embryo and embryo
      placement 0.5 cm from the center of the particle dispersion cone. Under these
      conditions, transformation efficiency was 100%, survival rate 25% and the number
      of expression units in the embryo body cells ranged from 100 to 1,000. Expression
      of green fluorescent protein was also detected in embryos bombarded under optimal
      conditions. Based on the results obtained, the biolistic process can be
      considered an efficient method for the transformation of chicken embryos and
      therefore can be used as a model system to study transient gene expression and
      tissue-specific promoters.

PMID- 11514835
TI  - von Willebrand factor antigen levels in plasma of patients with malignant breast
      disease.
AB  - von Willebrand factor (vWF) is a protein that mediates platelet adherence to the
      subendothelium during primary hemostasis. High plasma vWF concentrations have
      been reported in patients with various types of cancer, such as head and neck,
      laryngeal and prostatic cancer, probably representing an acute phase reactant. In
      the present study we determined the plasma levels of vWF antigen (vWF:Ag) by
      quantitative immunoelectrophoresis in 128 female patients with breast cancer as
      well as in 47 women with benign breast disease and in 27 healthy female controls.
      The levels of vWF:Ag were 170.7 +/- 78 U/dl in patients with cancer, 148.4 +/- 59
      U/dl in patients with benign disease and 130.6 +/- 45 U/dl in controls (P<0.005).
      We also detected a significant increase in the levels of vWF:Ag (P<0.0001) in
      patients with advanced stages of the disease (stage IV = 263.3 +/- 113 U/dl,
      stage IIIB = 194.0 +/- 44 U/dl) as compared to those with earlier stages of the
      disease (stage I = 155.3 +/- 65 U/dl, stage IIA = 146.9 +/- 75 U/dl). In
      conclusion, vWF levels were increased in plasma of patients with malignant breast
      disease, and these levels correlated with tumor progression.

PMID- 11514836
TI  - Detection of human parvovirus B19 in a patient with hepatitis.
AB  - Parvovirus B19 has been associated by some investigators with cases of severe
      hepatitis. The aim of the present study was to determine the presence of active
      parvovirus B19 infection among 129 Brazilian patients with non-A-E hepatitis. The
      patients were assayed for antibodies against parvovirus B19, IgM class, by ELISA.
      In IgM-positive cases, parvovirus B19 DNA was assayed by PCR in serum and liver
      tissue and parvovirus VP1 antigen in liver tissue was assayed by
      immunohistochemistry. Antibodies against parvovirus B19, IgM class, were detected
      in 3 (2.3%) of 129 patients with non-A-E hepatitis. Previous surgery and blood
      transfusions were reported by these 3 patients. One patient was a 56-year-old
      female with severe hepatitis, with antimitochondrial antibody seropositivity and
      submassive necrosis at liver biopsy, who responded to corticosteroid therapy.
      Strong evidence for active parvovirus B19 infection was found in this patient,
      with parvovirus B19 DNA being detected by PCR in liver tissue. Furthermore,
      parvovirus VP1 antigen was also detected in liver tissue by immunohistochemistry.
      The other two IgM-positive patients were chronic hepatitis cases, but active
      infection was not proven, since neither viral DNA nor antigen were detected in
      their liver tissues. This and other reports suggest a possible relation between
      parvovirus B19 infection and some cases of hepatitis.

PMID- 11514837
TI  - Effect of metabolic control on parathyroid hormone secretion in diabetic
      patients.
AB  - The metabolic derangement caused by diabetes mellitus may potentially affect bone
      mineral metabolism. In the present study we evaluated the effect of diabetes
      metabolic control on parathyroid hormone (PTH) secretion during stimulation with
      EDTA infusion. The study was conducted on 24 individuals, 8 of them normal
      subjects (group N: glycated hemoglobin - HbA1C = 4.2 +/- 0.2%; range = 3.5-5.0%),
      8 patients with good and regular metabolic control (group G-R: HbA1C = 7.3 +/-
      0.4%; range = 6.0-8.5%), and 8 patients with poor metabolic control (group P:
      HbA1C = 12.5 +/- 1.0%; range: 10.0-18.8%). Blood samples were collected at 10-min
      intervals throughout the study (a basal period of 30 min and a 2-h period of EDTA
      infusion, 30 mg/kg body weight) and used for the determination of ionized
      calcium, magnesium, glucose and intact PTH. Basal ionized calcium levels were
      slightly lower in group P (1.19 +/- 0.01 mmol/l) than in group N (1.21 +/- 0.01
      mmol/l) and group G-R (1.22 +/- 0.01 mmol/l). After EDTA infusion, the three
      groups presented a significant fall in calcium, but with no significant
      difference among them at any time. Basal magnesium levels and levels determined
      during EDTA infusion were significantly lower (P<0.01) in group P than in group
      N. The induction of hypocalcemia caused an elevation in PTH which was similar in
      groups N and G-R but significantly higher than in group P throughout the infusion
      period (+110 min, N = 11.9 +/- 2.1 vs G-R = 13.7 +/- 1.6 vs P = 7.5 +/- 0.7
      pmol/l; P<0.05 for P vs N and G-R). The present results show that PTH secretion
      is impaired in patients with poorly controlled diabetes.

PMID- 11514838
TI  - Dietary fiber intake, stool frequency and colonic transit time in chronic
      functional constipation in children.
AB  - The objective of the present study was to evaluate associations between fiber
      intake, colonic transit time and stool frequency. Thirty-eight patients aged 4 to
      14 years were submitted to alimentary evaluation and to measurement of colonic
      transit time. The median fiber intake of the total sample was age + 10.3 g/day.
      Only 18.4% of the subjects presented a daily dietary fiber intake below the
      levels recommended by the American Health Foundation. In this group, the median
      left colonic transit time was shorter than in the group with higher dietary fiber
      intake (11 vs 17 h, P = 0.067). The correlation between stool frequency and
      colonic transit time was negative and weak for left colon (r = -0.3, P = 0.04),
      and negative and moderate for rectosigmoid and total colon (r = -0.5, P<0.001 and
      r = -0.5, P<0.001, respectively). The stool frequency was lower in the group with
      slow transit time (0.8 vs 2.3 per week, P = 0.014). In conclusion, most patients
      with chronic functional constipation had adequate dietary fiber intake. The
      negative correlation between stool frequency and colonic transit time increased
      progressively from proximal segments to distal segments of the colon. Patients
      with normal and prolonged colonic transit time differ in terms of stool
      frequency.

PMID- 11514839
TI  - A high-fructose diet induces insulin resistance but not blood pressure changes in
      normotensive rats.
AB  - Rats fed a high-fructose diet represent an animal model for insulin resistance
      and hypertension. We recently showed that a high-fructose diet containing
      vegetable oil but a normal sodium/potassium ratio induced mild insulin resistance
      with decreased insulin receptor substrate-1 tyrosine phosphorylation in the liver
      and muscle of normal rats. In the present study, we examined the mean blood
      pressure, serum lipid levels and insulin sensitivity by estimating in vivo
      insulin activity using the 15-min intravenous insulin tolerance test (ITT, 0.5 ml
      of 6 microg insulin, iv) followed by calculation of the rate constant for plasma
      glucose disappearance (Kitt) in male Wistar-Hannover rats (110-130 g) randomly
      divided into four diet groups: control, 1:3 sodium/potassium ratio (R Na:K) diet
      (C 1:3 R Na:K); control, 1:1 sodium/potassium ratio diet (CNa 1:1 R Na:K); high
      fructose, 1:3 sodium/potassium ratio diet (F 1:3 R Na:K), and high-fructose, 1:1
      sodium/potassium ratio diet (FNa 1:1 R Na:K) for 28 days. The change in R Na:K
      for the control and high-fructose diets had no effect on insulin sensitivity
      measured by ITT. In contrast, the 1:1 R Na:K increased blood pressure in rats
      receiving the control and high-fructose diets from 117 +/- 3 and 118 +/- 3 mmHg
      to 141 +/- 4 and 132 +/- 4 mmHg (P < 0.05), respectively. Triacylglycerol levels
      were higher in both groups treated with a high-fructose diet when compared to
      controls (C 1:3 R Na:K: 1.2 +/- 0.1 mmol/l vs F 1:3 R Na:K: 2.3 +/- 0.4 mmol/l
      and CNa 1:1 R Na:K: 1.2 +/- 0.2 mmol/l vs FNa 1:1 R Na:K: 2.6 +/- 0.4 mmol/l, P <
      0.05). These data suggest that fructose alone does not induce hyperinsulinemia or
      hypertension in rats fed a normal R Na:K diet, whereas an elevation of sodium in
      the diet may contribute to the elevated blood pressure in this animal model.

PMID- 11514840
TI  - Heterogeneous response of adipose tissue to cancer cachexia.
AB  - Cancer cachexia causes disruption of lipid metabolism. Since it has been well
      established that the various adipose tissue depots demonstrate different
      responses to stimuli, we assessed the effect of cachexia on some biochemical and
      morphological parameters of adipocytes obtained from the mesenteric (MES),
      retroperitoneal (RPAT), and epididymal (EAT) adipose tissues of rats bearing
      Walker 256 carcinosarcoma, compared with controls. Relative weight and total fat
      content of tissues did not differ between tumor-bearing rats and controls, but
      fatty acid composition was modified by cachexia. Adipocyte dimensions were
      increased in MES and RPAT from tumor-bearing rats, but not in EAT, in relation to
      control. Ultrastructural alterations were observed in the adipocytes of tumor
      bearing rat RPAT (membrane projections) and EAT (nuclear bodies).

PMID- 11514841
TI  - Influence of acute renal failure on the mononuclear phagocytic system.
AB  - Several studies show the ability of macrophages to remove particles injected into
      the bloodstream. This function seems to be increased in the presence of acute
      renal failure. The objective of the present study was to assess the phagocytic
      function of the main organs (spleen, liver and lung) of the mononuclear
      phagocytic system in renal and postrenal failures. Fifteen rats (250-350 g) were
      divided into three groups (N = 5): group I - control; group II - ligature of both
      ureters, and group III - bilateral nephrectomy. On the third postoperative day,
      all animals received an iv injection of 1 ml/kg 99mTc sulfur colloid. Blood
      samples were collected for the assessment of plasma urea, creatinine, sodium, and
      potassium concentrations and arterial gasometry. Samples of liver, spleen, lung
      and blood clots were obtained and radioactivity was measured. Samples of liver,
      spleen, lung and kidney were prepared for routine histopathological analysis.
      Plasma urea, creatinine and potassium concentrations in groups II and III were
      higher than in group I (P<0.05). Plasma sodium concentrations in groups II and
      III were lower than in group I (P<0.05). Compensated metabolic acidosis was
      observed in the presence of postrenal failure. Group II animals showed a lower
      level of radioactivity in the spleen (0.98) and lung (2.63), and a higher level
      in the liver (105.51) than control. Group III animals showed a lower level of
      radioactivity in the spleen (11.94) and a higher level in the liver (61.80), lung
      (11.30) and blood clot (5.13) than control. In groups II and III liver steatosis
      and bronchopneumonia were observed. Renal and postrenal failures seem to
      interfere with blood clearance by the mononuclear phagocytic system.

PMID- 11514842
TI  - Ligand-induced endocytosis and nuclear localization of angiotensin II receptors
      expressed in CHO cells.
AB  - A construct (AT1R-NF) containing a "Flag" sequence added to the N-terminus of the
      rat AT1 receptor was stably expressed in Chinese hamster ovary cells and
      quantified in the cell membrane by confocal microscopy after reaction with a
      fluorescein-labeled anti-Flag monoclonal antibody. Angiotensin II bound to AT1R
      NF and induced endocytosis with a half-time of 2 min. After 60-90 min,
      fluorescence accumulated around the cell nucleus, suggesting migration of the
      ligand-receptor complex to the nuclear membrane. Angiotensin antagonists also
      induced endocytosis, suggesting that a common step in the transduction signal
      mechanism occurring after ligand binding may be responsible for the ligand
      receptor complex internalization.

PMID- 11514843
TI  - Effects of central imidazolinergic and alpha2-adrenergic activation on water
      intake.
AB  - Non-adrenergic ligands that bind to imidazoline receptors (I-R), a selective
      ligand that binds to alpha2-adrenoceptors (alpha2-AR) and mixed ligands that bind
      to both receptors were tested for their action on water intake behavior of 24-h
      water-deprived rats. All drugs were injected into the third cerebral ventricle.
      Except for agmatine (80 nmol), mixed ligands binding to I-R/alpha2-AR such as
      guanabenz (40 nmol) and UK 14304 (20 nmol) inhibited water intake by 65% and up
      to 95%, respectively. The selective non-imidazoline alpha2-AR agonist, alpha
      methylnoradrenaline, produced inhibition of water intake similar to that obtained
      with guanabenz, but at higher doses (80 nmol). The non-adrenergic I-R ligands
      histamine (160 nmol, mixed histaminergic and imidazoline ligand) and imidazole-4
      acetic acid (80 nmol, imidazoline ligand) did not alter water intake. The results
      show that selective, non-imidazoline alpha2-AR activation suppresses water
      intake, and suggest that the action on imidazoline sites by non-adrenergic
      ligands is not sufficient to inhibit water intake.

PMID- 11514844
TI  - Neonatal handling and the expression of immunoreactivity to tyrosine hydroxylase
      in the hypothalamus of adult male rats.
AB  - Neonatal handling has long-lasting effects on behavior and stress reactivity. The
      purpose of the present study was to investigate the effect of neonatal handling
      on the number of dopaminergic neurons in the hypothalamic nuclei of adult male
      rats as part of a series of studies that could explain the long-lasting effects
      of neonatal stimulation. Two groups of Wistar rats were studied: nonhandled (pups
      were left undisturbed, control) and handled (pups were handled for 1 min once a
      day during the first 10 days of life). At 75-80 days, the males were anesthetized
      and the brains were processed for immunohistochemistry. An anti-tyrosine
      hydroxylase antibody and the avidin-biotin-peroxidase method were used. Tyrosine
      hydroxylase-immunoreactive (TH-IR) neurons were counted bilaterally in the
      arcuate, paraventricular and periventricular nuclei of the hypothalamus in 30
      microm sections at 120-microm intervals. Neonatal handling did not change the
      number of TH-IR neurons in the arcuate (1021 +/- 206, N = 6; 1020 +/- 150, N = 6;
      nonhandled and handled, respectively), paraventricular (584 +/- 85, N = 8; 682 +/
      62, N = 9) or periventricular (743 +/- 118, N = 7; 990 +/- 158, N = 7) nuclei of
      the hypothalamus. The absence of an effect on the number of dopaminergic cells in
      the hypothalamus indicates that the reduction in the amount of neurons induced by
      neonatal handling, as shown by other studies, is not a general phenomenon in the
      brain.

PMID- 11514845
TI  - Metabolic markers following beta-adrenoceptor agonist infusion in footshock
      stressed rats.
AB  - Stress hormones can alter metabolic functions in adipose tissue and liver, as
      well as the sensitivity of rat white adipocytes and rat atrial responses to beta
      adrenergic agonists. In this study, we examined the effects of three daily
      footshock stress sessions on the plasma corticosterone, glucose, glycerol and
      triacylglycerol levels of fed, conscious male rats, and on the plasma glucose,
      glycerol and triacylglycerol levels of the same rats following iv infusions of
      beta-adrenergic agonists (isoproterenol: 0.4 nmol kg-1 min-1, noradrenaline: 5.0
      microg kg-1 day-1, and BRL 37344 ([+/-]-[4-(2-[(2-[3-chlorophenyl]-2
      hydroxyethyl)amino]propyl)phenoxy]acetic acid), a selective beta3-adrenoceptor
      agonist: 0.4 nmol kg-1 min-1). Plasma corticosterone levels increased
      significantly after each stress session, while triacylglycerol levels increased
      after the first session and glucose increased after the second and third
      sessions. Glycerol levels were unaltered after stress. These results suggest that
      repeated footshock stress may induce a metabolic shift from triacylglycerol
      biosynthesis to glucose release by hepatic tissue, with glycerol serving as one
      of the substrates in both pathways. Stressed rats were more sensitive to infusion
      of noradrenaline plus prazosin and to infusion of isoproterenol, with elevated
      plasma glucose, glycerol and triacylglycerol levels. The higher sensitivity of
      stressed rats to isoproterenol and noradrenaline was probably related to the
      permissive effect of plasma corticosterone. Only BRL 37344 increased plasma
      glycerol levels in stressed rats, probably because beta3-adrenoceptors are not
      involved in hepatic triacylglycerol synthesis, thus allowing glycerol to
      accumulate in plasma.

PMID- 11514846
TI  - Is the infertility in hypothyroidism mainly due to ovarian or pituitary
      functional changes?
AB  - The objective of the present study was to examine whether hypothyroidism affects
      the reproductive system of adult female rats by evaluating ovarian morphology,
      uterus weight and the changes in serum and pituitary concentrations of prolactin
      and gonadotropins. Three-month-old female rats were divided into three groups:
      control (N = 10), hypothyroid (N = 10), treated with 0.05% 6-propyl-2-thiouracil
      (PTU) in drinking water for 60 days, and T4-treated group (N = 10), receiving
      daily sc injections of L-thyroxine (0.8 microg/100 g body weight) during the last
      10 days of the experiment. At the end of 50 days of hypothyroidism no hypothyroid
      animal showed a regular cycle, while 71% of controls as well as the T4-treated
      rats showed regular cycles. Corpora lutea, growing follicles and mature Graafian
      follicles were found in all ovaries studied. The corpora lutea were smaller in
      both the hypothyroid and T4-replaced rats. Graafian follicles were found in 72%
      of controls and only in 34% of hypothyroid and 43% of T4-treated animals. Serum
      LH, FSH, progesterone and estradiol concentrations did not differ among the three
      groups. Serum prolactin concentration and the pituitary content of the three
      hormones studied were higher in the hypothyroid animals compared to control. T4
      treatment restored serum prolactin concentration to the level found in controls,
      but only partially normalized the pituitary content of gonadotropins and
      prolactin. In conclusion, the morphological changes caused by hypothyroidism can
      be a consequence of higher prolactin production that can block the secretion and
      action of gonadotropins, being the main cause of the changes observed.

PMID- 11514847
TI  - Respiratory mechanics and morphometric changes during anesthesia with ketamine in
      normal rats.
AB  - Ketamine is believed to reduce airway and pulmonary tissue resistance. The aim of
      the present study was to determine the effects of ketamine on the resistive,
      elastic and viscoelastic/inhomogeneous mechanical properties of the respiratory
      system, lungs and chest wall, and to relate the mechanical data to findings from
      histological lung analysis in normal animals. Fifteen adult male Wistar rats were
      assigned randomly to two groups: control (N = 7) and ketamine (N = 8). All
      animals were sedated (diazepam, 5 mg, ip) and anesthetized with pentobarbital
      sodium (20 mg/kg, ip) or ketamine (30 mg/kg, ip). The rats were paralyzed and
      ventilated mechanically. Ketamine increased lung viscoelastic/inhomogeneous
      pressure (26%) compared to the control group. Dynamic and static elastances were
      similar in both groups, but the difference was greater in the ketamine than in
      the control group. Lung morphometry demonstrated dilation of alveolar ducts and
      increased areas of alveolar collapse in the ketamine group. In conclusion,
      ketamine did not act at the airway level but acted at the lung periphery
      increasing mechanical inhomogeneities possibly resulting from dilation of distal
      airways and alveolar collapse.

PMID- 11514848
TI  - A new millennium, a new century, and new and greater challenges.

PMID- 11514849
TI  - For a general theory of health: preliminary epistemological and anthropological
      notes.
AB  - In order to conduct a preliminary evaluation of the conditions allowing for a
      General Theory of Health, the author explores two important structural dimensions
      of the scientific health field: the socio-anthropological dimension and the
      epistemological dimension. As a preliminary semantic framework, he adopts the
      following definitions in English and Portuguese for two series of meanings:
      disease = patologia, disorder = transtorno, illness = enfermidade, sickness =
      doenca, and malady = molestia. He begins by discussing some sociological theories
      and biomedical concepts of health-disease, which, despite their limitations, can
      be used as a point of departure for this undertaking, given the dialectical and
      multidimensional nature of the disease-illness-sickness complex (DIS). Second, he
      presents and evaluates some underlying socio-anthropological theories of disease,
      taking advantage of the opportunity to highlight the semeiologic treatment of
      health-disease through the theory of "signs, meanings, and health practices".
      Third, he analyzes several epistemological issues relating to the Health theme,
      seeking to justify its status as a scientific object. Finally, the author focuses
      the discussion on a proposal to systematize various health concepts as an initial
      stage for the theoretical construction of the Collective Health field.

PMID- 11514862
TI  - [Historical and methodological aspects of the measurement and prediction of basal
      metabolic rate: a review].
AB  - This paper reviews the most relevant aspects of measuring basal metabolic rate
      (BMR). The authors discuss individual and lifestyle factors (age, anthropometry,
      smoking, physical activity, diet, menses, and ethnicity) as well as possible
      environmental factors at time of measurement which may alter BMR values. Various
      available predictive equations, especially those recommended by the World Health
      Organization in 1985, and subsequent validation studies, particularly in
      populations living in the tropics, are presented. The review indicates the need
      for more information on BMR from populations living in different parts of the
      world so that better estimates can be provided for clinicians and
      epidemiologists.

PMID- 11514863
TI  - [Health services utilization: a systematic review of related factors].
AB  - Health services utilization is determined by various factors. In order to study
      which factors are most important in different countries, a systematic review was
      conducted from 1970 to 1999. The mean number of visits, proportion of persons who
      see a doctor, and proportion that concentrate the most visits were similar.
      Children, childbearing-age women, and the elderly use health care services the
      most. Lower-income and less educated groups are also significantly associated
      with more frequent utilization. Increased health needs mediate more frequent
      utilization by these groups. However, the poorest groups may not receive adequate
      care, depending on the respective type of health system. Health need is one of
      the most important determinants in utilization, and if a health system's equity
      is to be analyzed, one must consider patterns of utilization among social groups
      in relation to the level of greatest need. Regularly visiting the same physician,
      a characteristic of accessibility to health care services, can determine more
      adequate utilization. This factor can reduce differences in health care among
      groups. The authors conclude by proposing a hierarchy of related factors.

PMID- 11514864
TI  - Differences and similarities in sexual and contraceptive knowledge, attitudes,
      and behavior among Latino male adolescent students in California, United States
      and Lima, Peru.
AB  - To identify the differences and similarities in sexual and contraceptive
      knowledge, attitudes, and behavior among Latino male adolescent students living
      in California and Lima. Self-administered, anonymous surveys were completed by
      Latino male students aged 12-19 participating in California, and by male
      adolescent students in four high schools in Lima. Both surveys contained similar
      questions allowing for comparisons regarding sexual activity and contraceptive
      behavior. The mean age of male students were 16 and 15 years, respectively. More
      California males reported having engaged in sexual intercourse (69% vs 43%. The
      sexual debut was 13 years in both samples. More students in California were aware
      of their risk of pregnancy at first sexual intercourse than in Lima (82% vs 50%).
      One-third of the California males reported communicating with their partner about
      sex and contraception to be "easy" as compared to 53% of males in Lima. More
      students in California reported knowing a place to obtain contraceptives if they
      need them (85% vs 63%), having ever gotten someone pregnant (29% vs 7%), and
      having fathered a child (67% vs 16%).

PMID- 11514865
TI  - [Detection of triatomines (Hemiptera: Reduviidae) in domiciliary and extra
      domiciliary ecotopes. Corrientes, Argentina. ].
AB  - In order to identify intra- and extra-domiciliary triatomines, a study in
      different counties of Corrientes Province, Argentina, was conducted from 1985 to
      1995. Triatoma infestans (Klug, 1834), Triatoma sordida (Stal, 1859),
      Panstrongylus geniculatus (Latreille, 1811), and Panstrongylus megistus
      (Burmeister, 1835) were detected in domestic ecotopes. T. infestans and T.
      sordida were also found in the peridomicile. Triatoma platensis (Neiva, 1913),
      Psammolestes coreodes (Bergroth, 1911), T. sordida, and Triatoma rubrovaria
      (Blanchard, 1843) were collected in sylvatic biotopes. T. infestans was confirmed
      as the predominant species in the domestic environment and was the only species
      infected with Trypanosoma cruzi-like parasites. T. sordida was most frequent in
      extra-domiciliary ecotopes, but could be considered capable of colonizing human
      dwellings.

PMID- 11514866
TI  - [The making of AIDS news].
AB  - This study is part of the overall research effort on the role of the media in
      making sense of events in late modernity. The main objective is to investigate
      the context in which news about AIDS is produced at the interface between norms
      for producing news (as expressed by professional journalists) and an analysis of
      news stories published in four mainstream Brazilian newspapers. The results are
      organized in three broad topics: (a) the construction of news about AIDS; (b) the
      visibility of AIDS news during the study period; and (c) factors that facilitate
      or hinder the production of AIDS news. Important factors include exclusiveness of
      the story and/or novelty of the content, the notion of hot (or cold) news, and
      the specific contents. The authors also emphasize the inevitable chance elements
      associated with organizational characteristics and daily journalism. They
      conclude by pointing to recent changes in both the shape of the AIDS epidemic and
      the communications dynamics resulting from recent developments in the electronic
      media.

PMID- 11514867
TI  - [AIDS, activism, and the regulation of clinical trials in Brazil: Protocol 028].
AB  - This paper examines the politics and practices of drug evaluation in Brazil. It
      traces the history of AIDS activists' influence on the organization of modern
      clinical trials and their scientific rationale. Using the Merck indinavir trial
      as a case study, the authors discuss how organized civil society has developed
      strategies to intervene in the course of drug evaluation trials, shaping them
      according to its own interests. Adopting translation sociology as the theoretical
      framework, the paper describes and analyzes the strategies used by activists from
      "Grupo PelaVidda/SP" (an AIDS NGO) to build a consensus concerning indinavir
      monotherapy's lack of efficacy. The study considers the several regulatory forums
      involved in dealing with the controversy during the trial period.

PMID- 11514868
TI  - [Non-adherence to tuberculosis treatment: a study on perceptions and knowledge of
      the disease and evaluation of health services from the patient perspective].
AB  - This research was developed in 1995-1996 in the Oliveira Pombo Health Center
      (CSOP), Fortaleza, Ceara, Brazil. The aim was to explore factors influencing non
      adherence to tuberculosis treatment. Specific objectives were: dynamics of
      tuberculosis notification and treatment of non-adherence cases at the CSOP;
      demographic, social, economic, and cultural profiles of clientele (social
      actors); default reasons that interrupt treatment; and knowledge and perception
      of the disease. The methodological approach was based on descriptive epidemiology
      and on sociological interpretivism. A semi-structured interview was used for
      questions related to the social actors, such as: demographic, social, economic,
      cultural, and behavioral factors; knowledge and perceptions of tuberculosis and
      treatment; impact of the disease on patients' lives; and perspectives concerning
      health service attendance. Results show that treatment non-compliance involved
      multiple and complex interrelated factors.

PMID- 11514869
TI  - [Social network and social support measures from the Pro-Saude Study: pre-tests
      and pilot study].
AB  - We describe methodological steps in the selection of questions on social networks
      and support for a cohort study of 4,030 employees from a public university in Rio
      de Janeiro. First, group discussions with volunteers were conducted to explore
      the adequacy of related concepts. Next, questions in the Medical Outcomes Study
      questionnaire were submitted to standard "forward-" and "back-translation"
      procedures. The questions were subsequently evaluated through five stages of pre
      tests and a pilot study. No question had a proportion of non-response greater
      than 5%. Pearson correlation coefficients between questions were distant from
      both zero and unity; correlation between all items and their dimension score was
      higher than 0.80 in most cases. Finally, Cronbach Alpha coefficients were above
      0.70 within each dimension. Results suggest that social networks and support will
      be adequately measured and will allow for the investigation of their associations
      with health outcomes in a Brazilian population.

PMID- 11514870
TI  - [Control of malaria transmission in a gold-mining area in Amapa State, Brazil,
      with participation by private enterprise].
AB  - This paper reports on the epidemiological characterization of malaria following
      implementation of a program to control the endemic in a gold-mining area in
      northern Amapa State. The study focuses on total malaria cases in Amapa and the
      impact of the disease on the population, as represented by the Mineracao Novo
      Astro S/A company and its employees as well as the community of Vila de Lourenco
      in the municipality of Calcoene, and adjacent gold miners. The effect of control
      measures in the program area is indicated by a significant reduction in malaria
      incidence and malaria-related morbidity and mortality. The importance of
      participation by private enterprise is emphasized, particularly in large projects
      for the control of endemic diseases (notably malaria) in the Amazon Region.

PMID- 11514871
TI  - [Knowledge, attitudes, and practices related to the Pap smear among women with
      cervical cancer].
AB  - Despite screening programs, Brazil has a high cervical cancer mortality rate. The
      objective of this cross-sectional study was to analyze knowledge, attitudes, and
      practices related to the Pap smear and to understand why women fail to submit to
      this screening test. A structured questionnaire was used to interview 138 women:
      90 with high grade intraepithelial neoplasia and 48 with invasive cervical
      cancer. Inadequate practices were more frequent among women with invasive cancer.
      In terms of difficulties in obtaining medical care, more than 80% of women
      reported lack of motivation, 60% reported that physicians failed to conduct a
      complete physical examination, and some 50% reported that physicians' schedules
      were busy. Having a Pap smear usually depended on a physician's request and the
      woman being symptomatic. Women over than 56 years old showed more frequent
      inadequate knowledge, attitudes and practices. However, those with more schooling
      were more knowledgeable of the Pap smear procedure. Age and less schooling could
      be barriers against women participating in screening programs, but socioeconomic
      problems must also be considered for improving practices related to the Pap
      smear.

PMID- 11514872
TI  - [Occupational accidents in Botucatu, Sao Paulo, recorded by the Social Security
      System from 1995 to 1999].
AB  - This study describes workplace accidents recorded by the Social Security Office
      in Botucatu, Sao Paulo, from 1995 to 1999. Related work force information for the
      same period was obtained from the 8 largest industrial companies in the city.
      Data were coded and processed electronically. A total of 2,462 accidents were
      recorded. Of these, 87.3% were workplace accidents, 6.1% occurred while
      commuting, and 6.6% were occupational diseases. From 1996 to 1999 there was a
      reduction in workplace accidents reflecting a drop in accidents at the largest
      companies. Mean time-off-the-job due to accidents was greater in small companies
      (16.21 to 24.32 days) than in the large ones (9.83 to 12.78 days), with a
      statistical significance of alpha = 5% and p = 0.0001. THE RESULTS: (a) confirm
      that analyses based on number of officially recorded workplace accidents are
      limited; (b) show the importance of improving the quality of the system for
      recording workplace accidents in order to include all classes of workers, not
      only the registered work force; and (c) show that changes in company work
      management strategies are important to understand local changes in accident
      frequency.

PMID- 11514873
TI  - [Inequality of workers' survival in Botucatu, Sao Paulo State, Brazil].
AB  - The aim of this observational study was to estimate the survival function and
      risk of death in Botucatu, Southeast Brazil, by occupation. The occupational
      history of inhabitants of Botucatu who died after their 10th birthday from
      January 1, 1997, to March 31, 1998, was analyzed, as were the occupational
      histories of workers' spouses. A total of 992 subjects were studied. Data were
      analyzed by fitting a proportional hazards model where the time variable was age
      at death or at time of interview and the main co-variable was occupation. Results
      showed that risk of death increased consistently as the level of occupational
      specialization decreased, displaying a 12-year increase in life expectancy for
      professional as compared to unskilled workers.

PMID- 11514874
TI  - [Organized civil society and mental health issues in Rio de Janeiro: a
      democratization of social space].
AB  - This article discusses the importance of political action by three associations
      of mental health care users and family members: the Brazilian Association of
      Mental Care Patients, Friends, and Family (AFDM), the Society of General Services
      for Occupational Integration (SOSINTRA), and the Association of Relatives and
      Friends of Patients in the Juliano Moreira Psychiatric Facility (APACOJUM). Our
      aim is to increase the visibility of these associations and to foster innovation
      and collective forms of solidarity and mutual help in the health care field. The
      article analyzes the associations as special interest groups within a specific
      arena, the Rio de Janeiro Municipal Health Council.

PMID- 11514875
TI  - [Nutritional status of adolescents: "risk of overweight" and "overweight" in a
      public school in Sao Paulo].
AB  - This study aimed to assess the nutritional status of adolescents. A cross
      sectional study was taken in a public high school in Sao Paulo, Brazil, with 92
      students ages 11 to 17 years. The sample was performed using systematic
      statistical selection. Nutritional status of adolescents was assessed using body
      mass index (BMI), compared to WHO (1995) standards. Prevalence rates for "risk of
      overweight" and "overweight" were 27.9% and 4.6%, respectively, for boys, as
      compared to 10.2% and 16.3% for girls. Prevalence of "risk of overweight" and
      "overweight" was thus high for both sexes; the results were similar in comparison
      to other studies. In addition, the difference in nutritional status between
      genders was significant (p < 0.05).

PMID- 11514876
TI  - [Bioethical principles in public health: limitations and proposals].
AB  - We propose to analyze the specificity of ethical problems in public health issues
      and to elucidate the applicability of principlism as a problem-solving strategy
      in this realm. Although well-established in clinical ethics, principlism is not
      an adequate model to be used in public health, since it is basically intended to
      serve as a moral guide in the physician-patient encounter. We discuss the
      possible adequacy of principles like "solidarity", "ontic responsibility" (as
      proposed by Jonas), and "caring or diaconal responsibility" as presented by
      Levinas. Solidarity appears to be insufficiently specified, whereas the other two
      perspectives may be adapted to public health issues by bringing together Jonas'
      ontological and Levinas' transcendental concerns to form a principle of
      protection that might better serve the purposes of such an ethics. This principle
      would help to identify more clearly the goals and agents involved in the
      implementation of public policies that are expected to be both morally correct
      and pragmatically effective.

PMID- 11514877
TI  - [AIDS mortality in the State of Rio de Janeiro, 1991-1995].
AB  - This article focuses on the AIDS mortality profile as related to socioeconomic
      and geographic variables, as well as evaluating the impact of deaths from AIDS in
      the State of Rio de Janeiro. The analysis included all death certificates for
      residents of the State from 1991-1995, 10,024 of which had AIDS recorded as the
      primary cause of death. In the 20-49-year age bracket, among individuals who had
      died of AIDS, the proportion of those with university schooling (14%) and the
      proportion of single individuals (75%) were greater than the respective
      proportions for all other causes of death (5.4% and 56.3%). For the population as
      a whole, the AIDS mortality rate increased from 1991 to 1995, from 20.6/100,000
      to 30.2/100,000 for males and from 3.7/100,000 to 7.9/100,000 for females. For
      the year 1995 in the 20-49-year bracket, considering the 17 groups of causes from
      the ICD-9, AIDS was the third most common cause of death among men and the fifth
      most common among women. The proportion of Potential Loss of Life Years up to 65
      years as a function of AIDS increased from 1991 to 1995, from 3.4% to 4.7% for
      men and from 1.4% to 2.9% for women. During this same period there was also an
      increase in the number of counties in the State of Rio de Janeiro with reported
      deaths from AIDS.

PMID- 11514878
TI  - [Physical activity in a probabilistic sample in the city of Rio de Janeiro].
AB  - This study evaluated physical activity in a probabilistic sample of 4,331
      individuals 12 years of age and older residing in the city of Rio de Janeiro, who
      participated in a household survey in 1996. Occupation and leisure activity were
      grouped according to categories of energy expenditure. The study also evaluated
      number of hours watching TV, using the computer, or playing video-games. Only
      3.6% of males and 0.3% of females reported heavy occupational work. A full 59.8%
      of males and 77.8% of females reported never performing recreational physical
      activity, and there was an increase in this prevalence with age, especially for
      men. Women's leisure activities involved less energy expenditure and had a lower
      median duration than those of men. Mean daily TV/video/computer time was greater
      for women than for men. The greater the level of schooling, the higher the
      frequency of physical activity for both sexes. Analyzed jointly, these data show
      the low energy expenditure through physical activity by the population of the
      city of Rio de Janeiro. Women, the middle-aged, the elderly, and low-income
      individuals were at greatest risk of not performing recreational physical
      activity.

PMID- 11514879
TI  - [Social pediatrics and its reformist proposals].
AB  - This article reflects on the constitution of Social Pediatrics in Brazil, viewing
      it as a movement for reform in children's health care involving teaching,
      services, and pediatric practice. The article includes a historical and
      bibliographical review of the Social Pediatrics' field and the provision of
      children's health care, analyzing its relations with movements for the reform of
      medical education and health care and its conceptual framework, including several
      authors' definitions and formulations on the theme.

PMID- 11514880
TI  - [Nursing practice and public health policy in Campinas, Sao Paulo, Brazil].
AB  - Redemocratization in the 1970s brought about changes in the public health system
      in Brazil. The Unified National Health System (SUS) was implemented in 1988,
      based on local and regional administrative systems. This was an important step
      that resulted in greater local control and the introduction of new technologies.
      This study focuses on the local health system in Campinas, a relatively affluent
      and technologically advanced region some 100km from the city of Sao Paulo in
      Southeast Brazil. Qualitative and quantitative methods were used to evaluate the
      work of 233 nurses in the local health system. The first nurse was hired in 1977,
      and now there are 53 nurses working in specific areas: 10 in the central health
      administration, 36 in district administrations, and the rest in local services.
      Nursing services are organized in six main areas: administration, coordination of
      human resources, education, information technology, health surveillance, and
      health administration. Nursing intervention may be found in various areas, but it
      generally focuses on medical consultations, and there is little emphasis on
      collective activities and health promotion. Local health objectives can only be
      achieved by creating new practices that promote collective health.

PMID- 11514881
TI  - [UNIMED: history and characteristics of a Brazilian medical cooperative].
AB  - This article describes the organizational characteristics of the UNIMED medical
      cooperative in Brazil. After an overview of UNIMED's share in the current health
      plan market, the author analyzes its organizational structure, historical
      evolution, and contractual regimen with member physicians, including the formula
      used to calculate the payment schedule for physician services. The plan currently
      includes 367 local member cooperatives, operating in over 80% of Brazil's
      counties, with 41% of existing physicians to serve 7% of the population. The
      organization's history began with local cooperatives and subsequently
      federations, the confederation, and other companies in the group. The
      organizational design and dynamics favor a high degree of decentralization and
      autonomy, subordination of all components in the system to the physician
      cooperative command, and the occurrence of internal disputes and conflicts
      between individual interests and those of the organization.

PMID- 11514882
TI  - [The pyramid trap].
AB  - This paper discusses the impact of globalization on public health practice.
      Neoliberal supremacy has resulted in both greater interdependence between
      countries and increasing inequalities. Globalization of health risks and the
      dependence of local health conditions on external forces precludes the use of
      local/national solutions for global problems. In this context, the classical
      organization of public health services in a hierarchical pyramid based on
      geographically defined areas (from the local to the regional and national levels)
      no longer makes sense. We thus suggest some characteristics of a different type
      of organization based on new information technologies: a transnational network,
      horizontally shaped, more independent from political power, allowing for exchange
      of information and good practices, promoting dissemination of knowledge and
      producing "glocal" solutions. Through the creation of work opportunities between
      health professionals, the model will permit the creation of common strategies and
      increase the power of their political demands, perhaps allowing for the
      collective development of a more equitable world.

PMID- 11514883
TI  - [Historical issues in case-control studies].
AB  - This paper presents the main issues in the evolution of case-control studies
      (CCS) as of the late 1980s. The comparison of two groups regarding exposure to a
      risk factor has been known since the 18th century. The latter half of the 19th
      century witnessed a decline in the "Epidemiology of Populations", and the first
      CCS were only done in the 1920s. Improvement of the method occurred in the latter
      half of the 20th century, related to increased mortality from chronic diseases,
      especially in research on lung cancer and smoking. The main scientific
      contributions to the method were: use of the odds ratio as an estimate of
      relative risk; definition of statistical data analysis for retrospective studies;
      calculation of attributed risk and etiologic fraction; and discussion of the
      essence of CCS. Critics pointed to the method's possible weakness and
      susceptibility to bias. Application of CCS increased in the final decades of the
      20th century in various areas of Epidemiology and has been considered an
      important tool to improve Public Health.

PMID- 11514884
TI  - [Maternal educational level: correlation with obstetric indicators].
AB  - The aim of this study was to estimate associations between level of maternal
      education as the dependent variable and several variables present in birth
      certificates under the official Brazilian Ministry of Health model. A total of
      3,843 birth certificates were analyzed from Guaratingueta, Sao Paulo State, for
      singleton hospital deliveries in 1998. Statistically significant associations
      were found between low maternal educational level and low birth weight, 3 or more
      live births, history of stillbirth, and prenatal care including up to 6 visits.
      No association was found between abortions and preterm delivery as described in
      other studies, perhaps due to insufficient information. Maternal educational
      level can thus be considered an obstetric marker for some risk factors for the
      mother and infant.

PMID- 11514885
TI  - [Emergency contraception in Brazil: facilitators and barriers].
AB  - A multi-centered qualitative study was conducted in Brazil, Chile, and Mexico to
      assess the acceptability of emergency contraception both among potential users
      and possible providers, authorities, and opinion-makers, and to identify
      (according to participants' perceptions) factors facilitating or hindering the
      method's use and the most appropriate strategies to disseminate information and
      provide the method. Data were collected through semi-structured interviews, group
      interviews, and discussion groups, which were tape-recorded and transcribed. A
      thematic analysis of this material was conducted. Acceptability of emergency
      contraception was high among participants, who also felt that there were no
      barriers towards its acceptance by the population. Participants felt that the
      method's acceptability would be greater if it were included in reproductive
      health programs, emphasizing its prescription for emergency situations.
      Participants highlighted that strategic components in Brazil would be training of
      providers and inclusion of the method in family planning services.

PMID- 11514886
TI  - [Epidemiological surveillance of distribution of the caterpillar Lonomia obliqua
      Walker, 1855, in the State of Parana, Brazil].

PMID- 11514887
TI  - The value of the Ecological Station of Jatai's ecosystem services and natural
      capital.
AB  - The capacity of a given natural ecosystem to provide certain goods and services
      that satisfy human needs depends on its environmental characteristics (natural
      processes and components). It was described the availability of these goods and
      services (environmental functions) controlled and sustained by ecological
      processes operating in Ecological Station of Jatai (Luiz Antonio, SP). The
      environmental functions identified were grouped in four main categories. To make
      environmental values an integrated factor in planning and decision making it was
      assessed their socio-economic importance in qualitative terms and, if possible
      their monetary value. The combined potential annual return from identified
      functions of Ecological Station of Jatai is at least US$ 708.83/ha/year. In
      comparison to calculations made for other natural ecosystems this is a rather
      moderate estimate. The Ecological Station of Jatai is poorly protected and
      managed, it too is still threatened by human activity (agriculture) and many
      development plans. Although present day market economics do not recognize the
      monetary value of most environmental functions, such calculations do provide a
      revealing insight into the great socio-economic importance of Ecological Station
      of Jatai. More awareness of these values may provide an important incentive for
      their preservation and sustainable use.

PMID- 11514888
TI  - Responses to climatic factors by foragers of Plebeia pugnax Moure (in litt.)
      (Apidae, Meliponinae).
AB  - Flight activity of Plebeia pugnax Moure (in litt.) was studied in six colonies
      coming from Cunha, SP, from July to October 1994. Twice a week, from 8:00 a.m. to
      6:00 p.m., for 5 minutes every half-hour, all the bees entering and leaving the
      hives were counted. Six hundred counts were made and the materials that foragers
      carried were recorded. Data were analysed in relation to temperature, relative
      humidity, light intensity and day time. Foragers' flight activity was relatively
      constant in a wide range of temperature, from 22 degrees C to 34 degrees C. The
      minimum temperature for the beginning of flight activity was 14 degrees C.
      Effective flight activity (when foragers of all colonies were leaving the hives)
      occurred at 15 degrees C. These bees also flew within a wide range of relative
      humidity, from 30% to 100%, decreasing slowly after 50%. Flight activity
      increased as light intensity rose and it has also increased as the hours passed
      by, reaching a peak around midday and decreasing gradually afterwards. Pollen was
      collected all day long, while resin collection was relatively constant and debris
      transportation was slightly higher after 10:00 h. From all known Plebeia species,
      this one flew on the lowest temperature ever registered for this genus.

PMID- 11514889
TI  - Diel changes in food and feeding activity of sciaenid fishes from the South
      western Atlantic, Brazil.
AB  - Food habits and daily feeding activity of fish populations are important
      ecological variables for understanding their role in the ecosystem. Diel changes
      in feeding activity and dietary composition of juvenile whitemouth croaker
      Micropogonias furnieri, shortfin corvina Isopisthus parvipinnis, shorthead drum
      Larimus breviceps and of juvenile and adult banded croaker Paralonchurus
      brasiliensis were investigated from samples taken over a 24 hours period from 4
      to 5 September 1987 on the continental shelf off South-eastern Brazil. Whitemouth
      croaker and banded croaker had a benthic diet based on polychaetes and some
      caridean shrimps and showed no diel feeding pattern. Shortfin corvina and
      shorthead drum fed on crustaceans and teleostean fish, the former species
      primarily on pelagic sergestid shrimps and benthic caridean shrimps, and the
      latter mainly on pelagic sergestid shrimps, mysidacean and benthic caridean
      shrimps. Shortfin corvina is primarily a diurnal feeder, but preyed on some items
      only at night. Shorthead drum is a night feeder, with minimum stomach fullness
      values between dawn and daytime, and maximum values between dusk and night time.

PMID- 11514890
TI  - Food resource utilization of the skates Rioraja agassizii (Muller & Henle, 1841)
      and Psammobatis extenta (Garman, 1913) on the continental shelf off Ubatuba,
      South-eastern Brazil.
AB  - The feeding habits of Rioraja agassizii (syn. Raja agassizii) and Psammobatis
      extenta (syn. Psammobatis glansdissimilis) of the South-eastern Brazilian coast
      were studied by means of stomach content analysis. The samples were obtained on
      eight seasonal oceanographic cruises, carried out between October 1985 and July
      1987. The importance of each food item was evaluated on the basis of the Index of
      Relative Importance and the feeding similarity by Percentage of Similarity. The
      results indicated that both species are benthic feeders, preying mainly on
      Crustacea, especially Amphipoda, Caridea and Brachyura. Teleostei were also
      important for R. agassizii. Seasonal variation of the diet seems to be associated
      with the availability of the prey, whose distribution and abundance are related
      to the dynamics of the water masses of the region. Juveniles and adults of P.
      extenta exploited the same resources while juveniles and adults of R. agassizii
      presented low diet similarity during most of the year. Caridea were an important
      food for all length classes of R. agassizii, while Amphipoda were for smaller
      specimens, and Teleostei for larger ones. The feeding overlap between the two
      species was higher during autumn 1986, winter 1986 and winter 1987.

PMID- 11514891
TI  - Biodiversity assessment of benthic macroinvertebrates in altitudinal lotic
      ecosystems of Serra do Cipo (MG, Brazil).
AB  - Five lotic systems of Serra do Cipo, south-east Brazil, were investigated in
      order to assess the existing diversity of benthic macroinvertebrates, habitats
      microhabitats, and the available trophic resources. For each river it was
      analysed the communities of benthic macroinvertebrates and the composition of
      some taxonomic groups (Plecoptera, Ephemeroptera, Trichoptera and Diptera
      Chironomidae): the community with Bivalvia Sphaeriidae, Oligochaeta and
      Ephemeroptera Baetidae (being supposed a closed relation Bivalvia-Oligochaeta
      based on the process of bioturbation and enrichment of sediment in organic
      matter) in Tanque River; the macrofauna associated to aquatic macrophytes from
      rivers Peixe and Preto do Itambe reflecting the reaction of the ecosystems versus
      the quantities of nutrients which originate from the farmlands; the
      lithoreophilic communities of Cipo River; the community depending on deposits of
      leaves and filamentous algae in Congonhas Stream; the very rich community of the
      moss clumps in the Indaia Stream. A proposal for biological zonation of Cipo
      River and some comments about the importance of the analysed benthic
      macroinvertebrates in the biological production of the aquatic communities were
      done.

PMID- 11514892
TI  - Diversity and habitat preference of aquatic insects along the longitudinal
      gradient of the Macae River basin, Rio de Janeiro, Brazil.
AB  - Diversity and habitat preference of macroinvertebrates were studied in Macae
      River basin, Rio de Janeiro State, Brazil, along its longitudinal gradient. We
      selected stream reaches corresponding to 1st, 2nd, 4th, 5th and 6th orders. A
      Surber sampler was used to collect four macroinvertebrates samples of each
      substrate (sand, litter in pool areas, stones, and litter in riffle areas) during
      the three sampling periods, defined based on the rain regime: April (end of the
      rainy season), July (dry season), and October (beginning of the rainy season). We
      identified 46,431 specimens corresponding to 117 taxa. Analysis of diversity
      numbers (both for family or genus level) indicated that all insect taxonomic
      orders had higher numbers on 2nd order stream reach, except for Ephemeroptera, on
      4th order. However when considering morph-species taxonomic level, the higher
      diversity number occurred on 4th order stream. The highest richness and diversity
      numbers were found at the dry season. Considering habitat preference, both litter
      in pool areas and litter in riffle areas had the highest faunal richness.

PMID- 11514893
TI  - Habitat diversity and benthic functional trophic groups at Serra do Cipo,
      Southeast Brazil.
AB  - The assessment of the diversity of habitats and the characterisation of the
      functional trophic groups of benthic macroinvertebrate communities of some rivers
      of Serra do Cipo (MG) were the main objectives of this study. The available
      trophic resources and the types of substrata were characterised along with the
      structure and composition of their using functional trophic groups. Serra do Cipo
      is a watershed divisor of the Sao Francisco and Doce River basins, including a
      series of streams and rivers, of good water quality and well preserved ecological
      characteristics. Samples were collected in Cipo, Peixe and Preto do Itambe
      rivers, besides the Indaia and Capao da Mata streams at 26 sampling stations,
      during the rainy (February) and dry (October) seasons of 1998, using "Kicking
      nets" of 0.125 mm mesh size. The group of collectors (Baetidae, Leptophlebiidae
      and Leptohyphidae) was the most abundant, followed by collector-predators
      (Hydrophilidae, Ceratopogonidae, Chironomidae-Tanypodinae), and detritivorous
      herbivores (Oligochaeta). The riparian vegetation, together with the aquatic
      macrophytes, are the substrata containing the highest richness of functional
      trophic groups and the higher habitat diversity. The results suggest that the use
      of functional trophic groups, together with habitat evaluation, are efficient
      tools in the evaluation of the diversity of benthic macroinvertebrates,
      particularly in altitudinal lotic ecosystems.

PMID- 11514894
TI  - Feeding pattern of Salminus maxillosus (Pisces, Characidae) at Cachoeira das
      Emas, Mogi-Guacu River (Sao Paulo State, Southeast Brazil).
AB  - Diet of 364 specimens of the dourado (Salminus maxillosus) was studied monthly at
      Cachoeira das Emas from November/1996 to May/1998, considered the breeding ground
      of this and other migrant fishes of Mogi-Guacu River. Only adults were found at
      this site, and diet consisted exclusively of fish, with predominance of Leporinus
      sp. Seasonal variation in feeding activity was highest during some months of the
      rainy and hot season (September-December), when fish composition and number of
      prey species consumed also changed. These modifications were primarily attributed
      to an increase in food availability at the site of study during the rainy season,
      once most of the migrant species, including small Characidae concentrate there at
      this time of year. Apparently diet shifts, prey availability and rainfall are
      intimately related, representing a combination of factors that may account for
      the observed patterns of resource exploitation.

PMID- 11514895
TI  - Microbial respiration and chemical composition of different sediment fractions in
      waterbodies of the upper Parana River floodplain, Brazil.
AB  - Four size fractions of the sediment of six environments of the upper Parana River
      floodplain were analyzed for carbon, nitrogen, and phosphorus contents and
      microbial respiration (oxygen consumption). Particle size did not affect nitrogen
      and phosphorus content or microbial activity, but did affect carbon content (F =
      4.274, df = 3; 20, p = 0.020). The carbon concentration of ultra-fine particles
      was significantly lower than that of other sizes of sediment particles. Microbial
      respiration values were well predicted by sediment chemical composition, as shown
      by multiple regression (microbial respiration = -0.39 - 0.210C + 0.108N + 0.796P;
      F = 7.0495, p = 0.0022). However, phosphorus was the element which best explained
      the microbial respiration (partial coefficient = 0.796, p = 0.0039, n = 23).
      Considering that i) phosphorus was the best predictor of microbial respiration;
      ii) phosphorus is trapped in the series of reservoirs located upstream from the
      section of the floodplain studied; and iii) microbial respiration is a measure of
      decomposition rates and nutrient cycling, we hypothesize that the long-term
      accumulation of litter detritus and reduction of nutrient cycling in environments
      of the upper Parana River floodplain are probable impacts of this decrease in
      phosphorus caused by the upstream reservoirs.

PMID- 11514897
TI  - Spatial and temporal organization of aquatic insects assemblages in the
      longitudinal gradient of a tropical river.
AB  - The distribution and abundance of aquatic insects were studied in the
      longitudinal gradient of the watershed of Macae River, a coastal Atlantic Forest
      river in South-eastern Brazil. Sampling stations were selected in the first,
      second, fourth, fifth, and sixth orders and sampled in April, July, and October
      1995. This represented the end of the rainy season, the dry season, and the
      beginning of another rainy season, respectively. In each month four samples were
      collected using a Surber sampler from each of the following substrates: sand,
      litter deposited in pool areas, litter in riffle areas, and stones. A total of
      46,431 specimens of aquatic insects belonging to ten orders were obtained. The
      data were analyzed by the multivariate methodologies of Correspondence Analysis
      (CA) and Cluster Analysis (UPGMA) using the similarity index of Morisita, for all
      three months. Both showed a significant faunal disrupture in the river, which can
      be divided in two sections: the upper one, from first to fourth orders, and the
      lower section, including fifth and sixth orders. The same results were obtained
      with presence-absence matrices, using Jaccard similarity index, showing that the
      changes are not only due to quantitative differences. A Mantel test was used to
      compare the assemblage composition temporally and no difference was detected
      between the three months. Moreover, a Canonical Correspondence Analysis (CCA) was
      applied to the data to check which of the 14 physical and chemical variables
      significantly explained macroinvertebrate community variation. The most
      significant variables were conductivity, CPOM, and pH for the upper stations
      (1st, 2nd and 4th orders), and alkalinity, FPOM, and HCO(3) for the lower
      stations (5th and 6th orders).

PMID- 11514896
TI  - Thermal ecology and activity patterns of the lizard community of the Restinga of
      Jurubatiba, Macae, RJ.
AB  - We analyzed the thermal ecology and activity patterns of the lizard community
      from the Restinga of Jurubatiba, Rio de Janeiro, Brazil. The broadest activity
      was that of Tropidurus torquatus, a sit-and-wait forager, while the active
      foraging teiid Cnemidophorus littoralis had the shortest activity. The nocturnal
      gekkonid Hemidactylus mabouia was found active during the day only during early
      morning and late afternoon, when environmental temperatures are low. Body
      temperature was highest for Cnemidophorus littoralis and lowest for the two
      Mabuya species. The patterns found here are discussed and compared to those of
      congeneric species in other habitats in Brazil.

PMID- 11514898
TI  - Ichthyouris voltagrandensis n.sp. (Nematoda: Pharyngodonidae) from Myleus tiete
      Eigenmann & Norris, 1900 (Osteichthyes: Characidae) in the Volta Grande
      Reservoir, MG, Brazil.
AB  - The present work studied helminth parasites of "pacu-manteiga", Myleus tiete
      (Osteichthyes: Characidae) from Volta Grande Reservoir, MG, Brazil. Fishes with
      142.6 +/- 24.7 g weight and 17.3 +/- 1.0 cm total length were collected. Five out
      six analysed fish (prevalence 83.3%) were parasitized in the intestine with an
      average of 535.6 +/- 334.6 oxyurid nematodes per fish. The helminth was
      identified as Ichthyouris voltagrandensis n.sp. (Nematoda: Pharyngodonidae). It
      differs from I. brasiliensis (Moravec et al., 1992a) by the absence of lateral
      alae, higher measures of tail and caudal alae of males, esophageal isthmus
      length, distance of excretory pore from anterior end and spicule length. In
      addition, eggs were provided by two long filaments in just one pole and by the
      first time the authors observed flagellate spermatozoa from dissected males. The
      authors exposes comparative table of measures of the five described species of
      the genus Ichthyouris.

PMID- 11514899
TI  - Diurnal bird visiting of Caryocar brasiliense Camb. in Central Brazil.
AB  - Nectar of nocturnal flowers may be used by diurnal species that occasionally
      accomplish secondary pollination. Thirteen bird species visited Caryocar
      brasiliense flowers in central Brazil. There is a temporal separation between
      nectarivores and non-nectarivores species. Nectarivores birds visited flowers
      late in the morning, while other species appear earlier. C. brasiliense nectar
      may be an alternative resource to birds visitors during the dry season.

PMID- 11514900
TI  - Sentinels in Saltator atricollis (Passeriformes: Emberizidae).
AB  - I studied the existence of sentinels in Saltator atricollis in a 'campo-cerrado'
      (Brazilian savanna) during the breeding seasons of 1994-95 and 1995-96. Groups of
      this species consisted of two to seven birds (N = 25). Sentinels were present
      (mean +/- sd) 62% +/- 9% of the time, and most sentinel bouts lasted from less
      than one to six minutes (although in some occasions for more than 30 min.).
      Overlap of two or more sentinels occurred on average only 3.2% of the time with
      birds on guard. Sentinels commonly gave contact calls in the beginning and/or at
      the end of a sentinel bout. The group size had no effect on time with sentinels.
      However the encounter rate between raptors and groups significantly influenced
      the time guarded. The results of this study suggests that the ability of
      sentinels to detect predators may play a central role as an anti-predator device.

PMID- 11514901
TI  - Observations on the thermal selection of the pantanal caiman (Caiman crocodilus
      yacare) hatchlings (Crocodylia: Alligatoridae).
AB  - Three options of water temperatures in a thermal gradient that changed from 22 to
      35 degrees C were offered to Pantanal caiman (Caiman croocodilus yacare)
      hatchlings. Animals from two nests were submitted to temperatures during 19 days
      (Nest 1 -- 20 caimans caught in the nature hours after hatching), corresponding
      to 1 to 7 observations periods, and 13 days (Nest 2 -- 20 animals obtained by
      artificial incubation) relative to observation period 8. Caimans remain fasting
      during experimental period. Hatchlings were allocated in a enclosure containing
      three styrofoam boxes (120 L) disposed side by side enclosed by wire netting and
      filled with water to the top. Thus, the animals were free to access the boxes,
      which temperatures were changed at the end of each observation period to avoid
      position effects. Air temperature was keep close to 22 degrees C by air
      conditioning and water temperature was controlled by thermostats. The trial was
      divided in three phases determined by elimination of the less frequented
      temperature and its substitution by another temperature. In a first phase of the
      experiment that contained 1, 2 and 3 observation periods, the thermostats were
      regulated to 22 degrees C (BoxD), 26 degrees C (BxC) and 32 degrees C (BxA). In
      phase 2 to 26 degrees C, 29.5 degrees C (BxB) and 32 degrees C, including 4, 5
      and 6 periods. In the third phase that included 7 and 8 periods, the thermostats
      were adjusted to 29.5 degrees C, 32 degrees C and 35 degrees C (BxE). The number
      of caimans in each box was recorded two to three times a day (8:00, 14:00 and
      17:00h) before pointed water temperature. Mean water temperatures (+ standard
      deviation) and respective caiman frequency means by box/temperature were: Phase 1
      (BxD/22.3 +/- 1.2 degrees C - 10.3%; BxC/27.0 +/- 2.4 degrees C - 32.0% and
      BxA/31.2 +/- 1.1 degrees C - 57.6%); Phase 2 (BxC/26.6 +/- 2.8 degrees C - 13.3%;
      BxB/29.3 +/- 2.2 degrees C - 27.7% and BxA/31.3 +/- 1.2 degrees C - 59.0%) and
      Phase 3 (BxB/29.5 +/- 3.6 degrees C - 23.7%; BxA/31.0 +/- 2.2 degrees C - 31.9
      and BxE/34.0 +/- 2.2 degrees C - 44.4%). Observing that in the phases 1 and 2 the
      box with hottest water (CxA) was more frequented. In the phase 3, the difference
      between higher and smaller frequency straiten to 20.7%, in relation to almost
      46.5% in phases 1 and 2, indicating that water temperatures between 29.5 and 35
      degrees C resulted in body temperatures more next to the comfort zone, in the
      experimental conditions.

PMID- 11514902
TI  - Genotoxic evaluation of the effect of Thuya occidentalys tinctures.
AB  - Three tinctures samples from extracts of the popular medicinal plant Thuya
      occidentalis were tested in vitro through two short term tests for measuring the
      activity of genotoxic chemicals. Using the Salmonella/mammalian-microsome
      (Mutatest) assay and the SOS-chromotest (induction of beta-galactosidase in
      Escherichia coli), none of the extract was effective in inducing mutagenesis or
      beta-galactosidase synthesis (as an indicator of general and early sign of DNA
      damage), even with metabolization.

PMID- 11514903
TI  - Influence of the pineal gland on the physiology, morphometry and morphology of
      pancreatic islets in rats.
AB  - To investigate the influence of the pineal gland through melatonin secretion on
      the physiological and morphological parameters of pancreatic islets, we studied
      the plasma biochemistry and morphological and morphometric characteristics of the
      endocrine pancreas of male Wistar rats. The animals were distributed into five
      groups of ten rats each: NC - normal control group; NS -- sham-operated group; Px
      (25) -- pinealectomised group, studied 15--25 days after surgery; Px (70) --
      pinealectomised group, studied 60-70 days after surgery; ALX - alloxan
      monohydrate-treated group. Data are analyzed statistically by ANOVA and by the
      Kruskal-Wallis test. Although there was no significant difference in plasma
      glucose or insulin levels between the Px (25), Px (70) and NC groups, Px (25)
      animals showed a tendency to increased glucose and reduced insulin levels. The
      ALX group showed a clear elevation of plasma glucose and a reduction of plasma
      insulin compared to the other groups. Morphometric analysis showed a larger
      pancreatic islet area and a lower pancreatic islet density in the pancreas of Px
      (70) animals and an increase in degenerative pathological processes in the
      pancreatic islets of the Px (25) and ALX groups. The present results suggest that
      melatonin, in addition to acting on tissue sensitivity to insulin (as reported in
      other studies), affects the secretory action of beta cells, as demonstrated by
      the morphological and morphometric changes observed in pinealectomised animals.

PMID- 11514904
TI  - Histological processing techniques for the study of Dugesiidae development
      (Platyhelminthes, Tricladida, Paludicola).
AB  - The objective of the present study was to adapt techniques for the histological
      processing of Dugesiidae cocoons for the study of embryo development. The cocoons
      were fixed with formalin, SUSA, Bouin or paraformaldehyde/glutaraldehyde and
      subsequently embedded in Paraplast or glycol methacrylate (Historesin). Paraplast
      embedding yielded reasonable results only after the cocoon was perforated or
      fixed for a prolonged period of time using softening techniques with acid
      solutions. When the SUSA or Bouin fixative and Historesin embedding techniques
      were used the results were good for light microscopical analysis. Fixation with
      paraformaldehyde/glutaraldehyde and glycol methacrylate embedding resulted in
      better tissue preservation, and did not require prolonged fixation or softening
      techniques. Thus, we suggest this technique for light microscopical analysis of
      embryo development in Dugesiidae.

PMID- 11514905
TI  - Persistent asthma in adults: comparison of high resolution computed tomography of
      the lungs after one year of follow-up.
AB  - OBJECTIVE: The aims of this study were to evaluate the role of high resolution
      computed tomography of the thorax in detecting abnormalities in chronic asthmatic
      patients and to determine the behavior of these lesions after at least one year.
      METHOD: Fourteen persistent asthmatic patients with a mean forced expiratory
      volume in 1-second that was 63% of predicted and a mean forced expiratory volume
      in 1-second /forced vital capacity of 60% had two high resolution computed
      tomographies separated by an interval of at least one year. RESULTS: All 14
      patients had abnormalities on both scans. The most common abnormality was
      bronchial wall thickening, which was present in all patients on both computed
      tomographies. Bronchiectasis was suggested on the first computed tomography in 5
      of the 14 (36%) patients, but on follow-up, the bronchial dilatation had
      disappeared in 2 and diminished in a third. Only one patient had any
      emphysematous changes; a minimal persistent area of paraseptal emphysema was
      present on both scans. In 3 patients, a "mosaic" appearance was observed on the
      first scan, and this persisted on the follow-up computed tomography. Two patients
      had persistent areas of mucoid impaction. In a third patient, mucus plugging was
      detected only on the second computed tomography. CONCLUSIONS: We conclude that
      there are many abnormalities on the high resolution computed tomography of
      patients with persistent asthma. Changes suggestive of bronchiectasis, namely
      bronchial dilatation, frequently resolve spontaneously. Therefore, the diagnosis
      of bronchiectasis by high resolution computed tomography in asthmatic patients
      must be made with caution, since bronchial dilatation can be reversible or can
      represent false dilatation. Nonsmoking chronic asthmatic subjects in this study
      had no evidence of centrilobular or panacinar emphysema.

PMID- 11514906
TI  - Experience with the first Internet-based course at the Faculty of Medicine,
      University of Sao Paulo.
AB  - PURPOSE: The Internet expands the range and flexibility of teaching options and
      enhances the ability to process the ever-increasing volume of medical knowledge.
      The aim of this study is to describe and discuss our experience with transforming
      a traditional medical training course into an Internet-based course. METHOD:
      Sixty-nine students were enrolled for a one-month course. They answered pre- and
      post-course questionnaires and took a multiple-choice test to evaluate the
      acquired knowledge. RESULTS: Students reported that the primary value for them of
      this Internet-based course was that they could choose the time of their class
      attendance (67%). The vast majority (94%) had a private computer and were used to
      visiting the Internet (75%) before the course. During the course, visits were
      mainly during the weekends (35%) and on the last week before the test (29%).
      Thirty-one percent reported that they could learn by reading only from the
      computer screen, without the necessity of printed material. Students were
      satisfied with this teaching method as evidenced by the 89% who reported enjoying
      the experience and the 88% who said they would enroll for another course via the
      Internet. The most positive aspect was freedom of scheduling, and the most
      negative was the lack of personal contact with the teacher. From the 80 multiple
      choice questions, the mean of correct answers was 45.5, and of incorrect, 34.5.
      CONCLUSIONS: This study demonstrates that students can successfully learn with
      distance learning. It provides useful information for developing other Internet
      based courses. The importance of this new tool for education in a large country
      like Brazil seems clear.

PMID- 11514907
TI  - Activity of natural killer cells during HIV-1 infection in Brazilian patients.
AB  - Natural killer cells are increasingly being considered an important component of
      innate resistance to viruses, but their role in HIV infection is controversial.
      Some investigators have found that natural killer cells do not confer a
      protective effect during the progression of HIV disease, whereas others have
      shown that natural killer cells may be protective and retard the progression of
      the disease, either through their lytic activity or by a chemokine-related
      suppression of HIV replication. In this study, we analyzed functional alterations
      in the activity of natural killer cells during HIV-1 infection using a natural
      killer cells activity assay with K562 cells as targets. RESULTS: Our results show
      that the activity of natural killer cells decreases only in the advanced phase of
      HIV infection and when high (40:1) effector cell-target cell ratios were used.
      The depression at this stage of the disease may be related to increased levels of
      some viral factors, such as gp120 or gag, that interfere with the binding
      capacity of natural killer cells, or to the decreased production of natural
      killer cells -activity-stimulating cytokines, such as IFN-a and IL-12, by
      monocytes, a subset of cells that are also affected in the late stage of HIV
      infection. The data suggest that decreased natural killer cells cell activity may
      contribute to the severe impairment of the immune system of patients in the late
      stages of HIV infection.

PMID- 11514908
TI  - Prevention of respiratory syncytial virus infections.
AB  - Respiratory syncytial virus is the most important cause of viral lower
      respiratory illness in infants and children worldwide. By the age of 2 years,
      nearly every child has become infected with respiratory syncytial virus and re
      infections are common throughout life. Most infections are mild and can be
      managed at home, but this virus causes serious diseases in preterm children,
      especially those with bronchopulmonary dysplasia. Respiratory syncytial virus has
      also been recognized as an important pathogen in people with immunossupressive
      and other underlying medical problems and institutionalizated elderly, causing
      thousands of hospitalizations and deaths every year. The burden of these
      infections makes the development of vaccines for respiratory syncytial virus
      highly desirable, but the insuccess of a respiratory syncytial virus formalin
      inactivated vaccine hampered the progress in this field. To date, there is no
      vaccine available for preventing respiratory syncytial virus infections, however,
      in the last years, there has been much progress in the understanding of
      immunology and immunopathologic mechanisms of respiratory syncytial virus
      diseases, which has allowed the development of new strategies for passive and
      active prophylaxis. In this article, the author presents a review about novel
      approaches to the prevention of respiratory syncytial virus infections, such as:
      passive immunization with human polyclonal intravenous immune globulin and
      humanized monoclonal antibodies (both already licensed for use in premature
      infants and children with bronchopulmonary dysplasia), and many different
      vaccines that are potential candidates for active immunization against
      respiratory syncytial virus.

PMID- 11514909
TI  - Widespread hematogenous metastases and Trousseau's syndrome in gastric
      adenocarcinoma.
AB  - A case of widespread hematogenous metastases and Trousseau's syndrome is reported
      in a 40 year-old white housewife with gastric cancer, presenting subdural
      hematoma, ecchymoses, epistaxis, stomach and uterine bleeding. After undergoing
      hematoma drainage, she was unsuccessfully treated with platelets, red blood
      cells, plasma cryoprecipitate transfusions, and antibiotics. Necropsy disclosed
      gastric ring-signet adenocarcinoma invading the serous layer, with massive
      disseminated intravascular coagulation and systemic neoplastic embolism. Multiple
      old and recent hyaline (rich in fibrin and platelets) microthrombi, and tumor
      emboli were observed in the bone marrow, meninges, liver, lungs, kidneys, lymph
      nodes, adrenals, thyroid, heart, pancreas, and ovaries (Krukenberg tumor).

PMID- 11514910
TI  - Immunopathogenesis of scleroderma--evolving concepts.
AB  - Scleroderma, or systemic sclerosis, is a connective tissue disease which may
      affect various organ systems including skin, lungs, gastrointestinal tract,
      cardiovascular system and kidneys. While the etiology is not clear, it is
      currently believed that scleroderma may represent an autoimmune response to an
      unknown antigen. In this regard, there is evidence that both humoral and cellular
      immunity may play roles. The pathophysiology is complex and consists of three
      major features: (1) vascular damage; (2) mononuclear cellular infiltrates; and
      (3) massive deposition of newly synthesized connective tissue, mainly collagen.
      The major pathologic features of scleroderma and the roles of humoral and
      cellular immunity in its pathogenesis are reviewed and summarized.

PMID- 11514911
TI  - Skin cancer: a review and atlas for the medical provider.
AB  - Skin cancer is increasing in prevalence and is the most common form of cancer in
      young individuals. Descriptions of the clinical presentations of the most common
      skin cancers were derived from the author's clinical experience and a review of
      the literature. Photographs depicting the typical appearance of these lesions
      were collected, to facilitate recognition. Unique clinical characteristics of
      skin malignancy are described in the text and illustrated with photographs of the
      most typical presentation(s) of each of the common skin cancers. Early
      recognition leads to cure in most cases.

PMID- 11514912
TI  - Necrotizing fasciitis: a plea for early diagnosis and treatment.
AB  - INTRODUCTION: Necrotizing fasciitis is an uncommon infectious entity that poses
      difficult diagnostic and therapeutic management decisions. PURPOSE: This paper
      addresses the presentation, evaluation and management of the patient with a
      necrotizing soft tissue infection. CASE REPORT: A 54-year-old man presented to
      his physician with pain and swelling of the left anterior chest wall following a
      presumed insect bite several days prior. He was treated with oral antibiotics but
      returned to the office three days later with increased swelling, pain, and
      erythema in the axilla. Necrotizing fasciitis was diagnosed. He was hospitalized
      and taken to the operating room for debridement of the chest wall. Extensive
      necrosis of the skin, subcutaneous tissue and muscle was encountered. Muscle
      debridement extended from the pectoralis major and both obliques anteriorly to
      the latissimus dorsi and para-spinalis muscles posteriorly. Multiple operative
      debridements were performed over several days. The patient developed septic shock
      requiring blood pressure support, and multiple organ system failure requiring
      hemodialysis, prolonged ventilatory support and eventual tracheostomy. Split
      thickness skin grafts were placed during the third operative debridement and
      concluded on the 15th day of hospitalization. The patient eventually recovered
      and on the 53rd hospital day was transferred to the rehabilitation service, where
      he spent the next four weeks recovering movement in the left arm. CONCLUSION:
      Necrotizing fasciitis is an infectious entity that requires rapid diagnosis,
      surgical debridement, and tissue coverage if the patient is to survive.

PMID- 11514913
TI  - Update on panniculitis.
AB  - There is considerable confusion regarding the pathogenesis, nosology and
      treatment of panniculitis. This paper examines newer concepts in five types of
      panniculitis: i.e., histiocytic cytophagic panniculitis, erythema induratum,
      lipodermatosclerosis, pancreatic panniculitis and alpha-1-antitrypsin deficiency
      panniculitis. Recent developments in etiology, pathogenesis, molecular
      techniques, and therapy are discussed.

PMID- 11514914
TI  - Current therapy of pemphigus vulgaris.
AB  - Pemphigus vulgaris (PV) is a potentially fatal autoimmune blistering disease of
      the skin and mucous membranes, characterized by flaccid bullae that rupture and
      leave erosions. Its treatment is challenging. Although the use of systemic
      corticosteroids remains the cornerstone of effective therapeutic regimens for PV,
      their prolonged administration may lead to serious side effects. It is therefore
      necessary, for many patients, to add immunosuppressive agents or use
      immunomodulatory procedures to achieve remission. This paper will summarize the
      treatments available for PV, while focusing on the most recently available
      therapeutic options.

PMID- 11514915
TI  - The modern age of acne therapy: a review of current treatment options.
AB  - This review of current acne treatments begins with the crucial discovery in 1979
      of isotretinoin treatment for nodulocystic acne. This drug s approval in 1982
      revolutionized therapy, since it was the first oral acne-specific drug, and it
      provided prolonged remissions. In addition, it may prevent the emergence of
      resistant bacteria, a problem linked to the traditional use of antibiotics for
      acne. Patients who are not candidates for isotretinoin therapy may benefit from
      one of the other drugs or drug combinations reviewed, including the third
      generation topical retinoids adapalene and tazarotene, retinoic acid reformulated
      in new vehicles, azelaic acid, and topical antibiotics. Proper selection and
      education of patients are essential, since serious consequences may result from
      poorly monitored use of antibiotics and retinoid.

PMID- 11514916
TI  - Pyoderma gangrenosum.
AB  - Pyoderma gangrenosum (PG) is an idiopathic, painful and destructive condition
      that usually presents as an ulceration on the pretibial region of the legs. It
      primarily affects patients with inflammatory bowel disease, arthritis,
      myeloproliferative disorders and chronic hepatitis, and occasionally affects
      patients with other conditions, but it may also occur without any associated
      illness. Since there are no specific serologic or histologic markers for PG, it
      must be diagnosed clinically. Treatment usually involves immunosuppressant
      therapy as well as treatment of the underlying disease. The course of PG is
      unpredictable, and prognosis depends on the extent of the skin lesions at the
      time of diagnosis, underscoring the need for early and aggressive management.

PMID- 11514917
TI  - Evaluation and treatment of itching in HIV-infected patients.
AB  - Itching is a common complaint among patients infected with HIV and may cause
      significant morbidity and embarrassment. Although idiopathic HIV-pruritus has
      been described, it is probably less common than was previously thought. In most
      patients, a careful history and physical examination will show that a dermatosis
      accounts for their pruritus. Dry skin, seborrheic dermatitis, eczema, psoriasis,
      pruritic papular eruption, staphylococcal folliculitis and prurigo nodularis are
      frequently encountered in these patients. These common dermatoses, drug
      eruptions, several rarer conditions and systemic causes of itching should be
      excluded before diagnosing idiopathic HIV-pruritus. Treatment should be directed
      to the underlying skin problem and may be supplemented with sedating
      antihistamines. Phototherapy is a safe and effective therapeutic modality for
      many pruritic dermatoses as well as for idiopathic pruritus.

PMID- 11514918
TI  - Antique, archaic and arcane dermatologic instrumentation and armamentarium.
AB  - Numerous instruments and devices have been used by dermatologists, other
      physicians and lay practitioners through the ages to treat skin, hair, nails,
      venereal diseases, and fat. And there have often been overlaps among the antique,
      the arcane, the bogus, and the new.

PMID- 11514919
TI  - Unilateral, circumscribed, chronic dermatitis of the papillary-areolar complex:
      case report and review of the literature.
AB  - Lichen simplex chronicus is a well-described, common pruritic disorder resulting
      from repeated rubbing and scratching. Typically, only one site is involved. When
      this site involves the papillary-areolar complex of one breast, the condition is
      termed unilateral, circumscribed, chronic dermatitis of the papillary-areolar
      complex. A patient with this uncommon condition is herein reported, and the
      literature, including a discussion of the differential diagnosis, is reviewed. An
      aggressive approach to the work-up of such a patient is recommended, to ensure
      accurate diagnosis and initiation of appropriate therapy.

PMID- 11514920
TI  - Cutaneous granulomas masquerading as tuberculoid leprosy in a patient with
      congenital combined immunodeficiency.
AB  - Combined immunodeficiency disorders are characterized by abnormalities in
      cellular and humoral immunity. This classification includes common variable
      immunodeficiency (CVI), a primary immunodeficiency disorder characterized by
      hypogammaglobulinemia, recurrent bacterial infections, and significant T-cell
      abnormalities. Associated autoimmune diseases include rheumatoid arthritis,
      pernicious anemia, idiopathic thrombocytopenic purpura, and systemic lupus
      erythematous. Granulomatous lesions in lymphoid tissues, solid organs, and skin
      have been reported. We describe a patient with CVI who developed cutaneous
      granulomas with perineural invasion; to our knowledge, this is a previously
      undescribed feature.

PMID- 11514921
TI  - Childhood longitudinal melanonychia: case reports and review of the literature.
AB  - "Longitudinal melanonychia" refers to a brown or brown-black longitudinal band on
      a fingernail or toenail. A number of conditions can cause longitudinal
      melanonychia, but its main importance is that, in some patients, it may indicate
      the presence of a subungual malignant melanoma. Hyperpigmented nail bands are not
      uncommon in African-American, Latino and Asian patients, especially those over
      sixty years of age, and are often multiple in these groups. Longitudinal
      melanonychia is most worrisome when there is a solitary, dark, broad longitudinal
      band with pigment extending over the proximal nail fold (Hutchinson's sign). Such
      findings are considered to be a strong indication for biopsy of the nail matrix
      to rule out melanoma. Since nail matrix biopsy sometimes results in permanent
      nail deformity, and since the incidence of malignant melanoma is quite small in
      the pediatric age group, there is some controversy as to whether this procedure
      should routinely be performed in children. We report two cases of dramatic
      longitudinal melanonychia in toddlers and review the current literature on the
      management of this striking condition in the pediatric age group.

PMID- 11514922
TI  - Cutaneous polyarteritis nodosa after streptococcal necrotizing fasciitis.
AB  - Polyarteritis nodosa (PAN) is a necrotizing arteritis of small and medium-sized
      vessels. It may present with hypertension and/or renal insufficiency. Peripheral
      neuropathy, myopathy, joint pains, testicular pain, and ischemic myalgias may
      also be seen. Gastrointestinal involvement may lead to gangrene of the bowel,
      peritonitis, perforation, intra-abdominal hemorrhage, and pancreatitis. The
      cutaneous manifestations include tender subcutaneous nodules grouped along the
      course of superficial arteries of the lower extremities, with or without an
      overlying livedo reticularis. Although multisystem involvement is characteristic,
      sometimes only one organ or system may be involved. Associations with viral
      hepatitis (both B and C) and streptococcal infection have been established for
      PAN. Recurrent strep infections of the upper respiratory tract, streptococcal
      glomerulonephritis and rheumatic fever have previously been linked to PAN. This
      report extends the spectrum of associated streptococcal infections to include
      necrotizing fasciitis.

PMID- 11514923
TI  - Zosteriform Darier's disease versus acantholytic dyskeratotic epidermal nevus.
AB  - Patients with keratotic lesions distributed in a unilateral, linear, zosteriform
      or localized pattern and revealing histologic features of dyskeratotic
      acantholysis have been reported. There is still some controversy regarding the
      appropriate nosologic placement of this entity. Some believe it represents a
      localized form of Darier s disease, while others argue it is a variant of
      epidermal nevus. We report a case of a 42-year-old physician who presented with a
      15-year history of an asymptomatic eruption that had been diagnosed as "chronic
      zoster." Physical exam revealed hyperkeratotic papules and plaques in a
      dermatomal distribution. The controversy regarding the correct nosologic
      placement of such a patient is discussed.

PMID- 11514924
TI  - [Adjuvant drug treatment of alcoholism with acamprosate: between sectoral budgets
      and disease management].
AB  - OBJECTIVE: On the basis of several controlled clinical investigations the cost
      effectiveness of acamprosate as adjuvant therapy of alcohol-dependent patients
      has yet been evaluated. These optimal conditions cannot be found in the daily
      ambulant practice and results in asking which of the alternatives, "standard plus
      acamprosate" or "standard without acamprosate", is more cost-effective in
      maintaining abstinence in alcohol dependent patients under realistic conditions.
      PATIENTS AND METHODS: In an open multi-centre study, medical care, costs and
      therapeutic outcome was prospectively documented. Prior to enrolling, all
      patients were obliged to undergo a detoxification procedure. At a mean age of 45
      years the patients suffered an average of ten years from alcohol dependence. 521
      patients were documented in the acamprosate cohort and 265 patients in the cohort
      "other therapy" over one year. Two thirds of the participating patients were
      male. RESULTS: At 33.6 % the rate of abstinence was remarkably higher in the
      acamprosate cohort in comparison to the cohort "other" at 21.1 % abstinent
      patients. The mean total costs per patient and year amounted to DM 3191 in the
      acamprosate-cohort and were significantly lower than in the cohort "other" with
      DM 4046. Effectiveness-adjusted costs of DM 9500 per successfully treated patient
      in the acamprosate-cohort were superior to the cohort "other", amounting to DM 19
      148 per successfully treated patient. CONCLUSION: The described economic benefits
      may be utilised under conditions of an adequate disease management.

PMID- 11514925
TI  - [Retrospective analysis of fluconazole efficacy in Candida-colonized, non
      neutropenic, surgical patients in long-term intensive care].
AB  - BACKGROUND AND OBJECTIVE: The early clinical diagnosis of invasive candidiasis is
      difficult. Fluconazole, which has been available since the early 1990s, is a
      relatively atoxic intravenously applicable antimycotic agent. For this reason it
      has been widely used - possibly too much. The aim of this study was the
      retrospective critical evaluation of the efficacy of systemic antifungal
      chemotherapy in non-neutropenic, Candida-colonized, surgical patients in long
      term intensive care. PATIENTS AND METHODS: 69 patients (54 men and 15 women, aged
      55.8 [range 18-87] years) of 364 patients of the anaesthesiological intensive
      care unit (ICU) of the University Hospital of Heidelberg in 1991 and 1992 were
      selected for the study. None of the 69 patients was suffering from proven
      invasive candidiasis according to the gold-standard criteria of positive
      histology, blood culture, or isolation from a sterile compartment. However, 35 of
      the 69 patients were systemically treated with fluconazole (on average 295 mg per
      day for 10.2 days intravenously). 34 patients did not receive any antifungal
      therapy. Retrospectively we analysed the course of the disease in both groups of
      patients. Furthermore, 173 serum samples of these patients were available for
      investigations by Western blot for anti-Candida antibodies of the immune globulin
      classes M and G. RESULTS: Both groups, antimycotically treated and untreated
      patients, had similar characteristics at base-line: age, sex, underlying disease,
      severity of the disease (APACHE II Score), and also mortality (approximately 20 %
      in both groups). Only times in the ICU and on mechanical ventilation were
      significantly enhanced in fluconazole treated patients (p values 0.0004 each).
      Before therapy, the fluconazole patients had significantly more often yeasts in
      primarily non-sterile compartments (chi (2) test 0.05). The yeasts were partly
      eradicated by fluconazole (32/54, 59.3 %). Anti-Candida antibodies significantly
      correlated with higher age (anti 47 kDa antigen, p = 0.02), but not with other,
      clinically, diagnostically or prognostically relevant parameters. CONCLUSION:
      Fluconazole in non-neutropenic, Candida-colonized, surgical patients in long-term
      ICU care neither improved the clinical course nor the mortality rate among these
      patients. These observations indicate that there was a trend of overestimating
      the clinical significance of Candida in this group of patients. Fluconazole
      therapy may be significantly reduced in such patients.

PMID- 11514926
TI  - [Augmentation of left ventricular outflow tract gradient by digitalis glycosides
      in a case of cardiac (AL-) amyloidosis].
AB  - HISTORY AND CLINICAL FINDINGS: A 61-year-old man suffering from histologically
      confirmed amyloidosis associated with coagulation disturbances presented with
      exercise induced shortness of breath and symptoms of cardiac asthma after four
      cycles of chemotherapy with melphalan and prednisolone. As a result, treatment
      with digitoxin was initiated. In addition furosemide and an oral nitrate were
      administered. INVESTIGATIONS: Disparity between electrocardiogram and
      echocardiographic findings was observed in that, while the electrocardiogram
      showed loss of 'R wave in precordial leads V(2 - 4), excessive thickening of both
      left and right ventricular wall was shown in the echocardiogram. Doppler
      echocardiography revealed a left ventricular outflow tract obstruction at rest
      with a peak pressure gradient of 64 mm Hg which rose to 145 mm Hg during Valsalva
      manoeuvre. Colour Doppler presented a moderate mitral insufficiency and the
      transmitral Doppler flow studies detected a restrictive left ventricular filling
      pattern. DIAGNOSIS, TREATMENT AND COURSE: Digitalis therapy was stopped because
      of the outflow tract obstruction complicating cardiac amyloidosis. Cardiac
      symptoms abated over the following weeks. This improvement was reflected in a
      significant reduction of the outflow tract gradient, the gradients now being 16
      mm Hg under resting conditions and a maximum of 36 mm Hg during the Valsalva
      manoeuvre. The transmitral Doppler flow pattern showed a pseudonormalisation and
      the mitral regurgitation regressed nearly completely. The patient was free from
      cardiac complaints until his sudden death 21 months after the diagnosis of
      cardiac amyloidosis. CONCLUSION: Cardiac amyloidosis can present with left
      ventricular outflow tract obstruction mimicking hypertrophic obstructive
      cardiomyopathy. This fact must be borne in mind to avoid therapy with preload
      reducing or positive inotropic drugs and especially glycosides.

PMID- 11514927
TI  - [Mitochondrial diseases].

PMID- 11514928
TI  - [Provider profiling: needs, methodologic requirements and means to increase
      acceptance].

PMID- 11514929
TI  - [Patient's advance directives amidst legal decisions, medical objectivity and
      empathy].

PMID- 11514930
TI  - [Vestibular neuritis and benign paroxysmal postural dizziness].

PMID- 11514931
TI  - [Autopsy--as superfluous as goiter?].

PMID- 11514932
TI  - Demonstration of a cystine unit as a promising turn scaffold for the design of a
      parallel U-shaped two-helix bundle motif: crystal structure of the homodimer
      Cys(Aib(n))(2) (n = 3, 4).

PMID- 11514933
TI  - Universal similarity measure for comparing protein structures.
AB  - We introduce a new variant of the root mean square distance (RMSD) for comparing
      protein structures whose range of values is independent of protein size. This new
      dimensionless measure (relative RMSD, or RRMSD) is zero between identical
      structures and one between structures that are as globally dissimilar as an
      average pair of random polypeptides of respective sizes. The RRMSD probability
      distribution between random polypeptides converges to a universal curve as the
      chain length increases. The correlation coefficients between aligned random
      structures are computed as a function of polypeptide size showing two
      characteristic lengths of 4.7 and 37 residues. These lengths mark the separation
      between phases of different structural order between native protein fragments.
      The implications for threading are discussed.

PMID- 11514934
TI  - Refined molecular and crystal structure of silk I based on Ala-Gly and (Ala
      Gly)(2)-Ser-Gly peptide sequence.
AB  - The molecular and crystal structure of one of the crystalline modifications of
      Bombyx mori, silk I, was determined by x-ray diffraction method. Cell dimensions
      are essentially the same as those found in the synthetic model peptide poly(L-Ala
      Gly). The (straight phi, psi) values of L-Ala and Gly in the repeating unit are (
      112 degrees, -6 degrees ), and (71 degrees, -99 degrees ) respectively, which are
      in the Bridge and the forth quadrant regions of the Ramachandran map,
      respectively. The observed molecular conformation in the present study has a
      "crank-shaft" or a S-shaped zigzag arrangement, leading to a remarkable agreement
      of observed and calculated structure amplitudes for both dipeptide and
      hexapeptide sequences, and has a reasonable hydrogen bond networks. Obtained
      (straight phi, psi) values are quite different from those reported by Lotz and
      Keith, even though overall appearances are quite similar to each other. In spite
      of intra- and intermolecular hydrogen-bond networks, silk I structure changes
      easily to the silk II by a mechanical deformation. This fragility may be due to
      the above peculiar crank-shaft conformation deduced from the alternating
      structure of alanine and glycine.

PMID- 11514935
TI  - Derivation of the small-angle x-ray scattering functions for local conformations
      of polypeptide chains in solution.
AB  - The small-angle x-ray scattering (SAXS) functions are analytically derived for
      both the randomly coiled and helical local conformations of a polypeptide chain
      in solution. The resulting scattering functions for helices of various types are
      characterized by a maximum in the range of scattering-vector corresponding to
      Bragg spacings of 3-5 A, whereas the random-coil function has no maximum. This
      result is compatible with the extant SAXS data for partially neutralized poly(L
      glutamic acid) and poly(L-lysine) in aqueous solutions. Comparison of the SAXS
      data with the calculated scattering functions shows that helical structures in
      both polypeptide chains are of the 3.6(13)-helix (alpha-helix) rather than
      3.0(10)-type.

PMID- 11514936
TI  - Conformational effects of C(alpha,alpha)-dipropargylglycine as a constrained
      residue.
AB  - A useful synthon to approach artificial phenylalanyl peptides in a [2 + 2 + 2]
      cycloaddition reaction, C(alpha,alpha)-dipropargylglycine (Dprg) is examined for
      its conformational preferences as a constrained residue. Crystal structure
      analysis and preliminary NMR results establish possible preference of the residue
      for folded (alpha) rather than extended (beta) region of the straight phi,psi
      conformational space. Boc-Dprg-L-Leu-OMe (1) displays two molecular conformations
      within the same crystallographic asymmetric unit, with Dprg in the alpha(R) or
      alpha(L) conformation, participating in a type I beta-turn or an alpha(L)
      alpha(R)-type fold, in which Leu(2) assumes the alpha(R) conformation
      stereochemically favored for an L-chiral residue. Boc-Dprg-D-Val-L-Leu-OMe (2)
      displays a type I' beta-turn conformation in crystal, with both Dprg(1) and D
      Val(2) assuming the alpha(L) conformation stereochemically favored for a D-chiral
      residue, with 4 --> 1 type hydrogen bond linking L-Leu(3) NH with Boc CO. NMR
      analysis using temperature variation, solvent titration, and a spin probe study
      suggests a fully solvent-exposed nature of Dprg NH, ruling out a fully extended
      C(5)-type conformation for this residue, and solvent sequestered nature of L
      Leu(3) NH, suggesting possibility of a beta-turn due to Dprg assuming a folded
      conformation.

PMID- 11514937
TI  - A rheological study of the order-disorder conformational transition of xanthan
      gum.
AB  - The rheological properties of a moderately concentrated solution of xanthan gum
      in both the ordered and the disordered state have been studied. Oscillatory
      shear, steady shear flow, and extensional flow experiments have been performed at
      different temperatures, covering the order-disorder transition determined by
      differential scanning calorimetry (DSC). The principle of time/temperature
      superposition was applied to the xanthan solutions for the different types of
      flow. Although a master curve covering six decades of frequency could be obtained
      for the storage modulus over the entire investigated temperature range, less
      agreement was found for the other modulus. This indicates that the order-disorder
      transition reflects changes on the molecular scale and slight modification of the
      physical network structure. To the authors' knowledge, this is the first time
      that this transition has been observed using these different rheological
      techniques.

PMID- 11514938
TI  - Sequence patterns defining the 5' boundary of human genes.
AB  - In studies of both short and relatively long human genomic DNA, we found a
      clustering of the consensus site for the transcription factor GCF at the 5'
      boundary of a subset of human genes. In studies of promoter regions with known
      transcription initiation site, the cluster of consensus GCF site appeared near
      the transcription initiation site and in some sequences it extended into the
      transcribed region defining the leader mRNA. We also found a detectable
      correlation between the 5' boundary of human genes and recognition motifs for
      other transcription factors that bind to GC-rich sequences. But in these cases,
      the correlation was not as general as the correlation observed for the consensus
      GCF site.

PMID- 11514939
TI  - A helical arrangement of beta-substituents of dehydropeptides: synthesis and
      conformational study of sequential nona- and dodecapeptides possessing (Z)-beta
      (1-naphthyl)dehydroalanine residues.
AB  - Sequential nona- and dodecapeptides possessing three and four (Z)-beta -(1
      naphthyl)dehydroalanine (Delta(Z)Nap) residues, Boc-(L-Ala-Delta(Z)Nap-L-Leu)(n)
      OCH(3) (n = 3 and 4; Boc = t-butoxycarbonyl), were synthesized to design a rigid
      3(10)-helical backbone for a regular arrangement of functional groups using
      dehydropeptides. Their solution conformations were investigated by NMR and CD
      analyses, and theoretical energy calculations. Both peptides were found to adopt
      a 3(10)-helical conformation in CDCl(3) from their nuclear Overhauser effect
      spectroscopy (NOESY) spectra, which showed intense cross peaks for N(i)H-N(i+1)H
      proton pairs, but no cross peaks for C(alpha)(i)H-N(i+4)H pairs. The predominance
      of a 3(10)-helix was also supported by solvent accessibility of NH resonances. CD
      spectra of both peptides in tetrahydrofuran showed strong exciton couplets at
      around 228 nm assignable to naphthyl side chains, which are regularly arranged
      along a right-handed helical backbone. Chain-length effects on conformational
      preference in sequential peptide -(Ala-Delta(Z)Nap-Leu)(n)- were discussed based
      on spectroscopic analysis, energy minimization, and molecular dynamics
      simulations. Consequently, the repeating number n > or = 3 forms predominantly a
      right-handed 3(10)-helical conformation. The energy calculation also revealed
      that the midpoint naphthyl groups of peptide n = 4 are highly restricted to one
      stable orientation. In conclusion, beta-substituted alpha,beta-dehydroalanine is
      expected to be a unique tool for designing a rigid molecular frame of 3(10)-helix
      along which beta-functional groups are regularly arranged in a specific manner.

PMID- 11514940
TI  - Denaturation and aggregation of hen egg lysozyme in aqueous ethanol solution
      studied by dynamic light scattering.
AB  - We applied dynamic light scattering technique on the model system of hen egg
      lysozyme in salt-free aqueous ethanol solution to study the mechanism of
      denaturation and aggregation of protein. At low ethanol concentration [0-63%
      (v/v)], the fast relaxation mode was observed, which was caused by lysozyme
      molecules in the solution interacting with each other with strong repulsive
      electrostatic force. At 45 and 63% (v/v) ethanol, the slow relaxation mode was
      also observed, which showed translational diffusive nature, similar to that
      observed in salt-free polyelectrolyte solution. At 72 or 81% (v/v) ethanol, the
      slow mode disappeared, leaving only the fast mode. However, the mutual diffusion
      coefficients obtained from the fast mode at 72 and 81% (v/v) ethanol decreased by
      about one order of magnitude compared with those from the fast mode at 0-63%
      (v/v). The reported alcohol-induced conformational transformation of lysozyme
      molecules at >60% (v/v) ethanol from their native structure to an alpha-helix
      rich structure might cause such drastic decrease in the mutual diffusion
      coefficients. At the highest ethanol concentration of 90% (v/v), the slow mode
      reappeared, and its relaxation rate was decreasing with elapsed time, which is
      possibly due to the growth of aggregates of lysozyme molecules. X-ray diffraction
      results suggested that the intermolecular beta-sheet formation caused the
      aggregation. Thus, our results indicated that the change in molecular structure
      of lysozyme closely relates to the diffusion of molecules and their aggregation.

PMID- 11514941
TI  - Solution structure of the cytoplasmic linker between domain III-S6 and domain IV
      S1 (III-IV linker) of the rat brain sodium channel in SDS micelles.
AB  - The solution structure of the 36-mer peptide MP-5A in SDS micelles was
      investigated by CD and (1)H-NMR spectroscopies. The MP-5A was dissected from the
      cytoplasmic linker (K1482-A1517) connecting domain III-segment 6 (IIIS6) and
      domain IV-segment 1 (IVS1; III-IV linker) of the rat brain type IIA sodium
      channel. The molecular energy calculations including nuclear Overhauser effect
      and dihedral angle restraints gave a well-converged set of the structures of MP
      5A for the region between I1488 and S1506. It was found that a large hydrophobic
      cluster is formed by I1488-F1489-M1490 (IFM motif), Y1497-Y1498, and M1501, which
      may be related to the fast inactivation process of the sodium channel. The
      solvent-accessible surface area of the IFM motif (195 A(2)), which is known to
      work essentially as an inactivation gate particle to occlude the ion permeation
      pore, gave the free energy (DeltaG) of stabilization of -3.9 kcal mol(-1) as a
      result of the hydrophobic interactions with its receptor. This value agreed well
      with the free energy of binding (inactivation) of -4.1 kcal mol(-1) calculated
      for the equilibrium between the open and the inactivated states of the sodium
      channels. It is concluded that the fast inactivation of the sodium channel is
      achieved by the environmental polarity-dependent conformational switching at the
      IFM motif, in response to the voltage-dependent activation and the movement of
      the S4 segments of the sodium channel.

PMID- 11514942
TI  - Atlas of rat fetal skeleton double stained for bone and cartilage.
AB  - BACKGROUND: The double staining of fetal skeleton for bone and cartilage is a
      very useful method to evidence skeletal abnormalities in laboratory animals.
      However, this method has been rarely used in routine developmental toxicity
      tests. One reason could be the difficulty of comparing the single skeletal pieces
      and of having reference points. In this paper the fetal rat skeleton double
      stained with Alizarin red S and Alcyan Blue is described in detail to produce an
      atlas for developmental toxicity laboratories.

PMID- 11514943
TI  - Effects of maternal occupational exposure to organic solvents on offspring visual
      functioning: a prospective controlled study.
AB  - BACKGROUND: Previous studies in adults and animals with high level exposure to
      organic solvents suggested impairments in visual functioning. The objective of
      this pilot study was to examine the effects of maternal occupational exposure to
      organic solvents during pregnancy on offspring color vision and visual acuity,
      the development of which may be especially vulnerable to organic solvent
      exposure. METHODS: We conducted a prospective cohort study of 32 offspring of
      women who were exposed occupationally to organic solvents during pregnancy
      compared with 27 nonexposed children. Monocular and binocular color vision and
      visual acuity were assessed using the Minimalist Test and the Cardiff Cards,
      respectively. Children with known hereditary color vision loss were excluded.
      RESULTS: Solvent-exposed children had significantly higher error scores on red
      green and blue-yellow color discrimination, as well as poorer visual acuity
      compared with the control group. Exposure index (an estimated measure of exposure
      intensity) was not significantly related to color discrimination or visual acuity
      score. Despite excluding all children with a known family history of color vision
      loss, clinical red-green color vision loss was found among 3 of the 32 exposed
      children compared with none of the matched controls. CONCLUSIONS: These
      preliminary findings suggest that occupational exposure to organic solvents
      during pregnancy is associated with an increased risk of color vision and visual
      acuity impairment in offspring. The importance of routine visual function
      screening in risk assessment after prenatal exposure to chemicals warrants
      further attention.

PMID- 11514944
TI  - Continued occurrence of Accutane-exposed pregnancies.
AB  - BACKGROUND: Accutane a teratogenic prescription drug licensed to treat severe,
      recalcitrant nodular acne. First-trimester pregnancy exposure can cause major
      birth defects. The manufacturer began a Pregnancy Prevention Program (PPP) in
      1988; however, exposed pregnancies continue to occur. In 1996, the manufacturer
      began a direct-to-consumer advertising campaign, raising concerns of more exposed
      pregnancies. METHODS: We examined trends in Accutane use by reproductive-aged
      women. We also interviewed a series of 14 women in California who had recent
      Accutane-exposed pregnancies to identify opportunities for prevention. RESULTS:
      The estimated number of Accutane prescriptions for reproductive-aged women has
      more than doubled in the past 10 years; it is the most widely used teratogenic
      drug in the United States, with approximately 2.5 per 1,000 reproductive-aged
      women exposed to Accutane in 1999. One-half of the women interviewed reported
      seeing an advertisement for prescription acne treatment before taking Accutane.
      Eight of the 14 women used no contraception at the time of the exposed pregnancy;
      13 of the 14 women did not use two forms of contraception. Four of the 14 women
      did not have pregnancy tests before starting Accutane. None reported seeing all
      PPP components, and four saw only the information on the pill packet. These 14
      pregnancies resulted in four live infants who had no apparent birth defects, one
      live-born infant with multiple defects, four spontaneous abortions, and five
      induced abortions. CONCLUSIONS: The increase in Accutane use observed among
      females may be exacerbated by advertising. Physicians and patients must use more
      caution with teratogenic prescription drugs. Published 2001 Wiley-Liss, Inc.

PMID- 11514945
TI  - Interpretations of a teratogen warning symbol.
AB  - BACKGROUND: Warning symbols are used on teratogenic medications to communicate
      the message that women should (1) not take that medication if they may already be
      pregnant, and (2) not get pregnant while taking that medication. Communications
      research indicates that people interpret symbols or pictures in different ways.
      Other studies have shown that patients do not always receive education materials
      that are part of prescription protocol. Researchers at the Centers for Disease
      Control and Prevention (CDC) tested the interpretation of the teratogen warning
      symbol and its ability to convey the correct information without accompanying
      education. METHODS: A teratogen warning symbol currently printed on some
      medication packaging uses graphics and text warning the user not to get pregnant.
      Researchers interviewed women of childbearing age about their interpretation of
      the warning symbol and its meaning. Ninety-seven women were interviewed in a
      variety of locations, including public health clinics, literacy and job training
      offices, health clubs, and malls. RESULTS: Only 21% of women interpreted
      correctly without prompting that they should either not take the medication if
      they are pregnant or not get pregnant while taking the medication. Twenty-seven
      percent of women first thought the symbol meant the package contained birth
      control medication, and 24% said it simply indicated the package contained drugs
      or medicine. An additional 7% said they did not know what the symbol was supposed
      to mean; 39% of respondents offered circumstances in which prescription
      medications might be shared. CONCLUSIONS: Misinterpretation of warning symbols
      can result in serious consequences. This research should serve as an urgent call
      for mandating education for all patients receiving drugs with teratogenic
      properties, and careful pretesting and modification of warning symbols before
      they are used on medications with teratogenic effects. Published 2001 Wiley-Liss,
      Inc.

PMID- 11514946
TI  - Exposure-disease continuum for 2-chloro-2'-deoxyadenosine, a prototype ocular
      teratogen. 1. Dose-response analysis.
AB  - BACKGROUND: Treatment of pregnant mice with 2-chloro-2'-deoxyadenosine (2CdA) on
      day 8 of gestation induces microphthalmia through a mechanism coupled to the p53
      tumor suppressor gene. The present study defines 2CdA dosimetry with respect to
      exposure (pharmacokinetics), p53 protein induction, and disease (microphthalmia).
      METHODS: Pregnant CD-1 mice dosed with 0.5-10.0 mg/kg 2CdA on day 8 provided
      fetuses for teratological evaluation; 2CdA was measured by HPLC in the
      antimesometrium through 180 min postexposure, and p53 was assessed with
      immunostaining of the embryo through 270 min. 5'-/3'-RACE was used to sequence
      the candidate gene for 2CdA bioactivation from target cells. RESULTS:
      Microphthalmia appeared first in the dose-response curve. The highest 2CdA dose
      having no observable adverse effect (NOAEL) was 1.5 mg/kg; the benchmark dose
      that produced an extra 5% risk of microphthalmia (BMD(5)) was 2.5 mg/kg, and the
      lower confidence limit (BMDL) was 2.0 mg/kg. Pharmacokinetic parameters for doses
      encompassing the threshold (1.5-2.5 mg/kg) were modeled at 1.0-1.8 microM
      (C(max)) and 30-80 microM-min (AUC). The p53 response was not detected below the
      BMDL; however, a low-grade response appeared 4.5 hr after a teratogenic dose (5.0
      mg/kg), and high-grade induction followed an embryolethal dose (10.0 mg/kg). RACE
      identified a novel splice variant of mitochondrial deoxyguanosine kinase, dGK-3,
      as the likely candidate for 2CdA bioactivation in the embryo. CONCLUSIONS:
      Microphthalmia represented the critical effect malformation of 2CdA. The findings
      suggest a mitochondrial mechanism for 2CdA bioactivation, leading to an embryonic
      p53 response only after 2CdA elimination and implying pharmacodynamic coupling to
      the exposure-disease continuum. Published 2001 Wiley-Liss, Inc.

PMID- 11514947
TI  - Teratogen update: inorganic arsenic.
AB  - BACKGROUND: Inorganic arsenic has been used by many laboratories to study the
      pathogenesis of exencephaly in rodents. These studies, which used predominantly
      injection exposures, coupled with the paucity of epidemiology data, resulted in
      the erroneous inference that inorganic arsenic should be considered a human
      teratogen. METHODS: This study assembles and assesses literature analyses of
      older human and animal investigations together with the results of new
      experimental studies. These recent studies were performed according to modern
      regulatory guidelines, and relevant exposure routes (inhalation and ingestion)
      were used to evaluate the potential risk of developmental effects in humans.
      RESULTS: The existing epidemiological data are inadequate to support risk
      assessment because of the failure to confirm or measure arsenic exposure during
      early gestation and the deficiencies in accounting for potential confounding
      factors. The animal data revealed that inorganic arsenic caused malformations in
      offspring only when it was injected into the veins or peritoneal cavity of
      pregnant animals during early gestation. Exposure via inhalation or oral
      ingestion, even at concentrations that were nearly fatal to pregnant females,
      caused no arsenic-related malformations. CONCLUSIONS: Inorganic arsenic poses
      virtually no danger to developing offspring when maternal exposure occurs by
      relevant routes (oral and inhalation) at concentrations that are likely to be
      experienced in the environment or in the workplace.

PMID- 11514948
TI  - Pharmacokinetics of a new proton pump inhibitor, YJA-20379-8, after intravenous
      and oral administration to spontaneously hypertensive rats and DOCA-salt-induced
      hypertensive rats.
AB  - The purpose of this study was to investigate the causes for the differences
      observed in the pharmacokinetics of YJA-20379-8 in 16-week-old spontaneously
      hypertensive rats (SHRs). To see if the hereditary characteristics of SHRs was
      the cause, 20 mg/kg of the drug was intravenously infused over 15 min and 50
      mg/kg of the drug was orally administered to 6-week-old SHRs and 16-week-old SHRs
      and their age-matched control Kyoto-Wistar (KW) rats. Also to see if the
      hypertensive status itself was the cause, the same doses were administered to 16
      week-old deoxycorticosterone acetate (DOCA) salt-induced hypertensive rats (DOCA
      salt rats) and their age-matched control Sprague-Dawley rats. The areas under the
      plasma concentration-time curve from time zero to time infinity (for intravenous
      study) and to the last sampling time in plasma (for oral study) were
      significantly smaller after both intravenous and oral administration, and the
      total body clearances of the drug were significantly faster after intravenous
      administration to 6-week-old SHRs, 16-week-old SHRs, and 16-week-old DOCA-salt
      rats than those in their respective age-matched control rats. The above
      pharmacokinetic parameter changes in 16-week-old SHRs were due to both hereditary
      characteristic of SHRs and the hypertensive status itself.

PMID- 11514949
TI  - Comparative disposition of ricobendazole enantiomers after intravenous and
      subcutaneous administration of a racemic formulation to calves.
AB  - The enantioselective disposition kinetics of the benzimidazole anthelmintic,
      ricobendazole (RBZ), have been characterized after its intravenous (iv) and
      subcutaneous (sc) administration as a racemic formulation to cattle. The (+) and
      (-) RBZ enantiomeric forms were recovered in plasma after iv and sc
      administration of the racemic RBZ formulation, using a chiral phase based HPLC
      method. A biexponential plasma concentration versus time curve was observed for
      both RBZ enantiomers following the iv treatment. Total body clearance was higher
      for (-) RBZ (150.4 mL/h. kg) compared with that obtained for the (+) RBZ antipode
      (78.1 mL/h. kg). The elimination half-life of the (-) RBZ enantiomer was shorter
      (T1/2beta: 2.67 h) compared with the (+) enantiomer (T1/2beta: 5.41 h). The
      plasma availability (expressed as AUC) was significantly higher for (+) RBZ
      compared with that obtained for the (-) antipode following both treatments. The
      enantiomeric ratio in plasma at T(0) was close to unity (50% of each enantiomer);
      the analysis of the concentration ratios (+) RBZ/(-) RBZ, demonstrated an
      increase in the proportion of (+) RBZ during the time course of the kinetics
      after both iv and sc treatments. The results presented herein show the
      enantioselective disposition kinetics of RBZ in cattle and are a further
      contribution to the understanding of the kinetic behaviour of these sulphoxide
      containing benzimidazole anthelmintics in ruminants.

PMID- 11514950
TI  - Influence of dose on the distribution kinetics of ciprofloxacin and ofloxacin in
      the isolated hindlimb of the rat.
AB  - The aim of this study was to determine whether the dose influences the
      distribution kinetics of ciprofloxacin and ofloxacin in muscle- bone- and skin
      tissues included in the isolated hindlimb of the rat. Experiments were carried
      out in the isolated perfused hindlimb of the rat, administering a single dose of
      45, 450 or 900 microg of each quinolone as a bolus injection. Outflow perfusate
      samples were collected for 20 min and drug levels were determined by an HPLC
      technique. The mean transit time (MTT) and the distribution volume of
      ciprofloxacin significantly increased with the dose injected (MTT=1.47+/-0.69,
      8.74+/-0.27 and 9.52+/-2.95 min for 45, 450 and 900 microg, respectively). A
      similar situation was observed with ofloxacin, although the increase in these
      parameters was less pronounced (MTT=3.65+/-0.86, 7.92+/-2.03 and 8.32+/-1.70 min
      for 45, 450 and 900 microg, respectively). The distribution of ciprofloxacin and
      ofloxacin in the rat hindlimb appears to be a dose-dependent process, at least
      for the dose range considered in this study. This might explain the high
      variability in the distribution coefficients reported for these drugs in
      literature.

PMID- 11514951
TI  - Application of in vitro-in vivo correlations (IVIVC) in setting formulation
      release specifications.
AB  - An in vitro-in vivo correlation (IVIVC) was established for an osmotic controlled
      release dosage form by deconvolution using data from an immediate-release
      treatment as the characteristic response. The established IVIVC was evaluated
      internally (predicting data used to develop the IVIVC) and externally (predicting
      data not originally included in developing the IVIVC), and the application of the
      IVIVC in product development was demonstrated. The estimated in vivo dissolution
      profile compared favorably with the in vitro drug release profile. Good agreement
      was demonstrated between the estimated and observed cumulative drug release
      across the entire time course (level A correlation) with low (<10%) predictive
      error for both C(max) and AUC(infinity). External validation using lots not
      initially included in the model development compared very well with the observed
      in vivo profile, with mean prediction errors less than 10% for both C(max) and
      AUC(infinity). The proposed method demonstrates a schema for developing IVIVCs
      using data from biostudies routinely conducted during formulation development.
      The method should facilitate product optimization and can support setting in
      vitro dissolution specification.

PMID- 11514952
TI  - Urinary excretion of valproate metabolites in children and adolescents.
AB  - The objective of this communication is to describe the changes in the metabolic
      profile of valproic acid (VPA) from early to late childhood and adolescence. A
      cross-sectional study of 12 children and adolescents attending a neurological
      outpatients department, who were medicated with VPA, was carried out. The
      proportions of daily dose excreted as VPA-glucuronide, 3-oxo-VPA and 4-OH-VPA
      were calculated by relating 24-h recovery of these metabolites from urine to
      daily VPA dose. VPA, 3-oxo-VPA and 2-en-valproic acid (2-en-VPA) were measured in
      trough serum samples. VPA and its metabolites were measured using a capillary gas
      chromatograpy method. The proportion of daily dose recovered as VPA-glucuronide
      in children 10 years and younger was smaller than in older children (p<0.05).
      There were no differences between age groups in the recovery of the other
      measured metabolites. Lamotrigine (LTG) comedication was also associated with a
      higher proportion of VPA dose recovered as glucuronide (p<0.01). LTG comedication
      had a stronger association with a higher proportion of dose being recovered as
      VPA-glucuronide on multivariate analysis than did the age group (p=0.001 versus
      p<0.05). In conclusion, older children and adolescents, when compared with
      younger children, and those comedicated with LTG excrete a higher proportion of
      VPA dose as VPA-glucuronide.

PMID- 11514953
TI  - Effects of physostigmine on the pharmacokinetics of intravenous parathion in
      rats.
AB  - It was reported that the area under the plasma concentration-time curve from time
      zero to time infinity (AUC) of parathion was significantly smaller, and the time
      averaged total body clearance (Cl) of parathion was significantly faster after
      intravenous administration of parathion to rats pretreated with dexamethasone
      than those in control rats. This was supported by significantly faster intrinsic
      clearance of parathion to form paraoxon in hepatic microsomal fraction of rats
      pretreated with dexamethasone. The above data suggested that parathion was
      metabolized to paraoxon by dexamethasone-inducible hepatic cytochrome P450 (CYP)
      3A in rats. The purpose of this study is to explain the protective effects of
      physostigmine against paraoxon toxicity by suppressing CYP3A, and hence,
      decreasing formation of a toxic metabolite, paraoxon. The pharmacokinetic changes
      of parathion and paraoxon were investigated after intravenous administration of
      parathion, 3 mg/kg, to control Sprague-Dawley rats, and the rats pretreated with
      physostigmine (100 microg/kg, intraperitoneal injection 30 min before parathion
      administration). After a 1-min intravenous infusion of parathion to rats
      pretreated with physostigmine, the AUC of parathion (60.4 compared with 73.7
      microg min/mL) was significantly greater, Cl of parathion (49.7 compared with
      40.7 mL/min/kg) was significantly slower, and amount of paraoxon recovered from
      liver, mesentery and large intestine at 5 min was smaller than those in control
      rats. Based on in vitro rat hepatic microsomal studies, physostigmine inhibited
      significantly the erythromycin N-demethylase activity (1.03 compared with 0.924
      nmol/mg protein/min), mainly mediated by hepatic cytochrome P450 3A in rats. The
      above data suggested that the formation of paraoxon was inhibited in rats
      pretreated with physostigmine by inhibiting CYP3A.

PMID- 11514954
TI  - Use of automated microscopy for the detection of disseminated tumor cells in bone
      marrow samples.
AB  - The use of automated microscopy has reached the maturity necessary for its
      routine use in the clinical pathology laboratory. In the following study we
      compared the performance of an automated microscope system (MDS) with manual
      method for the detection and analysis of disseminated tumor cells present in bone
      marrow preparations from breast carcinoma patients. The MDS System detected rare
      disseminated tumor cells among bone marrow mononuclear cells with higher
      sensitivity than standard manual microscopy. Automated microscopy also proved to
      be a method of high reproducibility and precision, the advantage of which was
      clearly illustrated by problems of variability in manual screening. Accumulated
      results from two pathologists who had screened 120 clinical slides from breast
      cancer patients both by manual microscopy and by use of the MDS System revealed
      only two (3.8%) missed by the automatic procedure, whereas as many as 20 out of
      52 positive samples (38%) were missed by manual screening.

PMID- 11514955
TI  - Chromosomal imbalances in primary and metastatic melanomas revealed by
      comparative genomic hybridization.
AB  - Characteristic genetic changes underlying the metastatic progression of malignant
      melanoma is incompletely understood. The goal of our study was to explore
      specific chromosomal alterations associated with the aggressive behavior of this
      neoplasm. Comparative genomic hybridization was performed to screen and compare
      genomic imbalances present in primary and metastatic melanomas. Sixteen primary
      and 12 metastatic specimens were analyzed. We found that the pattern of
      chromosomal aberrations is similar in the two subgroups; however, alterations
      present only in primary and/or metastatic tumors were also discovered. The mean
      number of genetic changes was 6.3 (range 1-14) in primary and 7.8 (range 1-16) in
      metastatic lesions. Frequent losses involved 9p and 10q, whereas gains most often
      occurred at 1q, 6p, 7q, and 8q. Distinct, high-level amplifications were mapped
      to 1p12-p21 and 1p22-p31 in both tumor types. Amplification of 4q12-q13.1, 7q21.3
      qter and 8q23-qter were detected only in primary tumors. The 20q13-qter amplicon
      was present in a metastatic tumor. The number of genetic alterations were
      significantly higher in primary tumors which developed metastases within one year
      after the surgery compared to tumors without metastasis during this time period.
      Fluorescence in situ hybridization with centromeric and locus-specific probes was
      applied to validate CGH results on a subset of tumors. Comparison of FISH and CGH
      data gave good correlation. The aggressive behavior of melanoma is associated
      with accumulation of multiple genetic alterations. Chromosome regions, which
      differ in the primary and metastatic lesions, may represent potential targets to
      identify metastases-related chromosomal alterations.

PMID- 11514956
TI  - Different rates of CD4+ and CD8+ T-cell proliferation in interleukin-2-treated
      human immunodeficiency virus-positive subjects.
AB  - BACKGROUND: Interleukin-2 (IL-2) has been used successfully to increase CD4 cell
      counts in patients who are human immunodeficiency virus (HIV) positive. The
      mechanisms involved in this phenomenon are unknown. We hypothesized that a
      differential proliferation rate of CD4+ compared with CD8+ lymphocytes could be
      related to the increase of CD4 counts and of CD4/CD8 ratios that occur in HIV+
      patients during IL-2 treatment. METHODS: We enrolled in our study 14 HIV+
      patients treated with IL-2 or with highly active antiretroviral therapy (HAART)
      during a 96-week observation period. Using flow cytometry, we measured
      longitudinally the expression of the Ki67 antigen in peripheral blood CD4+ and
      CD8+ lymphocyte subsets. RESULTS: Compared with HAART alone, IL-2 produced a
      rapid increase of Ki67+ proliferating CD4 cells and a concomitant increase of the
      CD4/CD8 ratios, whereas the corresponding CD8 proliferation increased slightly.
      On the contrary, HAART alone was effective in suppressing equally both CD4 and
      CD8 proliferation. CONCLUSIONS: Our results suggest a selective activity of IL-2
      on CD4 T-cell proliferation; on the contrary, CD8-specific proliferation is
      affected minimally during treatment. This information may offer the potential to
      plan correctly immune activating regimens.

PMID- 11514957
TI  - Evaluation of an antibody-based genotype classification of the platelet
      fibrinogen receptor (GPIIb/IIIa).
AB  - Platelet membrane glycoprotein (GP) IIb/IIIa is the central molecule in platelet
      adhesion and aggregation by high-affinity binding of fibrinogen. Polymorphism of
      the beta chain of the receptor, especially the GPIIIa-proline33 allele [HPA-1b,
      Zwb, PI(A2)], has been suggested to be associated with a variety of vascular
      diseases, such as coronary stenosis, myocardial infarction, cerebral ischemia, or
      venous thrombosis. Using clinical chemistry standards, we evaluate a flow
      cytometric whole-blood, antibody-based method to determine the genotype
      [PI(A1A1), PI(A1A2), PI(A2A)] versus polymerase chain reaction (PCR)-based DNA
      restriction fragment length analysis in 220 individuals. Both homozygous and
      heterozygous genotypes differ in the expression of binding sites for the
      monoclonal antibody, SZ21. Agreement between the two methods was achieved in 187
      cases, which reflects a test validity of 85%, a sensitivity of 83.6%, and a
      specificity of 85.4%. We conclude that flow cytometry is reliable for classifying
      the PI(AX) genotype. The performance characteristics are easy, fast, and cheap
      (genomics by proteomics). These features make it suitable for screening patients
      and broad populations for the future risk of cardiovascular ischemic events.

PMID- 11514958
TI  - Relationship between oxidative burst activity and CD11b expression in neutrophils
      and monocytes from healthy individuals: effects of race and gender.
AB  - Oxidative burst activity and the expression of adhesion molecules have been used
      as indicators of leukocyte activation status. The aim of the study was to
      delineate the relationship of oxidative burst activity and the expression of
      adhesion molecules in neutrophils and monocytes from a pool of healthy volunteers
      (n = 96). We also tested the potential role of gender and a racial background in
      the individual response differences. Basal and phorbol myristate acetate (PMA)
      stimulated oxidative burst and CD11b expression were determined using
      dihydrorhodamine 123 and phycoerythrin (PE)-conjugated anti-CD11b monoclonal
      antibodies. PMA markedly increased CD11b expression and cellular oxidant content
      in neutrophils and monocytes in all samples. However, the responses showed
      considerable variability among individuals. A positive correlation was observed
      between the responsiveness of neutrophils and monocytes in their basal or PMA
      stimulated CD11b expressions and PMA-stimulated oxidative burst activities. In
      contrast, no correlation was found between the level of adhesion molecule
      expression and cellular oxidant content in monocytes or neutrophils either under
      basal or under PMA-stimulated conditions. The reactivity of oxidative burst
      (i.e., PMA-stimulated over basal) was significantly lower in neutrophils from
      African American males compared with cells from African American females, white
      females, or white males. In contrast, reactivity of monocytes was significantly
      elevated in white males compared with all other groups. These findings indicate
      that leukocytes with a relatively high degree of adhesion molecule expression may
      display an average or decreased oxidative burst activity, and vice versa. Our
      findings also indicate that ethnic background may influence the oxidative burst
      activity in neutrophils and monocytes. This needs consideration in clinical
      studies utilizing healthy volunteers with mixed gender and ethnic backgrounds.

PMID- 11514959
TI  - Preoperative prediction of postoperative edema and effusion in pediatric cardiac
      surgery by altered antigen expression patterns on granulocytes and monocytes.
AB  - Postoperative edema and effusion (POEE) following cardiopulmonary bypass (CPB)
      surgery in children retards recovery and may aggravate postpericardiotomy (PPS),
      capillary leak syndrome (CLS), or multiorgan failure (MOF). Compared with
      complication-free children, POEE affected children have different preoperative
      serum levels of circulating cytokines and adhesion molecules. These levels may be
      used preoperatively to assess POEE, but their determination is time consuming,
      costly, and a substantial blood volume is required. Altered serum levels of
      cytokines and adhesion molecules also may be reflected in altered antigen
      expression on circulating blood leukocytes. The predictive potential of flow
      cytometric (FCM) leukocyte immunophenotyping was explored as a sensitive and fast
      method that required small blood samples. Blood samples taken 24 h preoperatively
      from 49 patients (3-18 years old) were stained with monoclonal antibodies for
      adhesion molecules (ICAM-1, LFA-1, Mac-1) or constitutive/activation markers
      (CD4, CD14, CD16, CD25, CD54, CD69, HLA-DR) and measured on a microbead
      calibrated FCM. Neutrophils, monocytes, and eosinophils from POEE patients
      express higher preoperative levels of LFA-1, monocytes, HLA-DR, and other
      activation markers (all P < 0.03). Over 89% of the patients were classified
      correctly by using two discriminant analysis methods (sensitivity, >76%;
      specificity, >86%; positive prediction, >80%; negative prediction, >83%).
      Granulocytes and monocytes of postoperative POEE patients exhibit significant
      preoperative immune activation, suggesting an increased risk for patients with
      atopic/allergic predisposition. Surgical trauma and CPB cause additional immune
      activation, leading to POEE by a summative response. Most patients at risk for
      POEE can be identified preoperatively by using data pattern analysis on FCM
      derived parameters.

PMID- 11514960
TI  - Enumeration of CD34+ cells in cord blood: a variation on a single-platform flow
      cytometric method based on the ISHAGE gating strategy.
AB  - Single-platform flow cytometric absolute cell counting protocols provide
      increased robustness for CD34+ cell enumeration by limiting potential sources of
      imprecision. However, samples with any cellular fragmentation or debris, such as
      cord blood samples, provide challenges for these assays. We describe a simple,
      robust absolute CD34+ cell counting protocol, suitable for cord blood, using
      TRUCOUNT absolute count tubes (BD Biosciences, San Jose, CA) and a modified
      ISHAGE (International Society for Hematotherapy and Graft Engineering) gating
      strategy. An advantage of TRUCOUNT tubes is that each tube is supplied with a
      known number of lyophilized fluorescent beads. The method includes no-wash
      fixative-free ammonium chloride red blood cell lysis and the viability dye, 7
      amino actinomycin D, to exclude dead cells. The threshold was set on CD45
      expression in the FL1 channel and an exclusion gate in the forward scatter
      channel reduced debris. No manual adjustment of the gating regions was required,
      even for samples in less than optimal condition. Comparison of the TRUCOUNT
      ISHAGE protocol with the original dual-platform ISHAGE assay (n = 30) and the
      single-platform ISHAGE protocol using Flow-Count Fluorospheres (Beckman Coulter,
      Fullerton, CA; n = 22) showed high correlation (R(2) = 0.949 and 0.989,
      respectively) and no significant difference or bias for samples ranging from 22
      to 600 CD34+ cells per microliter. Results are presented that demonstrate the
      detrimental effect of a fixative-containing lysis reagent when used in a lyse-and
      wash procedure. The TRUCOUNT-ISHAGE protocol combines the attributes of TRUCOUNT
      tubes and the ISHAGE gating strategy to provide a single-platform protocol
      capable of achieving readily standardization of CD34+ cell enumeration.

PMID- 11514977
TI  - Peptides in frog brain areas processing visual information.
AB  - Vision is the most important sensory modality to anurans and a great deal of work
      in terms of hodological, physiological, and behavioral studies has been devoted
      to the visual system. The aim of this account is to survey data about the
      distribution of peptides in primary (lateral geniculate complex, pretectum,
      tectum) and secondary (striatum, anterodorsal and anteroventral tegmental nuclei,
      isthmic nucleus) visual relay centers. The emphasis is on general traits but
      interspecies variations are also noted. The smallest amount of peptide-containing
      neuronal elements was found in the lateral geniculate complex, where primarily
      nerve fibers showed immunostaining. All peptides found in the lateral geniculate
      complex, except two, occurred in the pretectum together with four other peptides.
      A large number of neurons showing intense neuropeptide thyrosine-like
      immunoreactivity was characteristic here. The mesencephalic tectum was the
      richest in peptide-like immunoreactive neuronal elements. Almost all peptides
      investigated were present mainly in fibers, but 9 peptides were found also in
      cells. The immunoreactive fibers show a complicated overlapping laminar
      arrangement. Cholecystokinin octapeptide, enkephalins, neuropeptide tyrosine, and
      substance P (not discussed here) gave the most prominent immunoreactivity.
      Several peptides also occur in the tectum of fishes, reptiles, birds, and
      mammals. Peptides in various combinations were found in the striatum, the
      anterodorsal- and anteroventral tegmental nucleus, and the isthmic nucleus that
      receive projections from the primary visual centers. The functional significance
      of peptides in visual information processing is not known. The only exception is
      neuropeptide tyrosine, which was found to be inhibitory on retinotectal synapses.

PMID- 11514978
TI  - Distribution and regulation of substance P-related peptide in the frog visual
      system.
AB  - Modulation of visual signal activity has consequences for both signal processing
      and for activity-dependent structuring mechanisms. Among the neuromodulatory
      agents found in visual areas are substance P (SP)-related peptides. This article
      reviews what is known about these substances in the amphibian retina and optic
      tectum with special emphasis on the leopard frog, Rana pipiens. It is found that
      the distribution of these SP-related peptides is remarkably similar to that seen
      in mammals. This suggests that study of model amphibian systems may significantly
      enhance our understanding of how neuropeptides contribute to visual system
      function and organization.

PMID- 11514979
TI  - Immunohistochemical distribution of enkephalin, substance P, and somatostatin in
      the brainstem of the leopard frog, Rana pipiens.
AB  - The brainstems of frogs contain many of the neurochemicals that are found in
      mammals. However, the clustering of nuclei near the ventricles makes it difficult
      to distinguish individual cell groups. We addressed this problem by combining
      immunohistochemistry with tract tracing and an analysis of cell morphology to
      localize neuropeptides within the brainstem of Rana pipiens. We injected a
      retrograde tracer, Fluoro-Gold, into the spinal cord, and, in the same frog,
      processed adjacent sections for immunohistochemical location of antibodies to the
      neuropeptides enkephalin (ENK), substance P (SP), and somatostatin (SOM). SOM+
      cells were more widespread than cells containing immunoreactivity (ir) to the
      other substances. Most reticular nuclei in frog brainstem contained ir to at
      least one of these chemicals. Cells with SOM ir were found in nucleus (n.)
      reticularis pontis oralis, n. reticularis magnocellularis, n. reticularis
      paragigantocellularis, n. reticularis dorsalis, the optic tectum, n.
      interpeduncularis, and n. solitarius. ENK-containing cell bodies were found in n.
      reticularis pontis oralis, n. reticularis dorsalis, the nucleus of the solitary
      tract, and the tectum. The midbrain contained most of the SP+ cells. Six
      nonreticular nuclei (griseum centrale rhombencephali, n. isthmi, n. profundus
      mesencephali, n. interpeduncularis, torus semicircularis laminaris, and the
      tectum) contained ir to one or more of the substances but did not project to the
      spinal cord. The descending tract of V, and the rubrospinal, reticulospinal, and
      solitary tracts contained all three peptides as did the n. profundus
      mesencephali, n. isthmi, and specific tectal layers. Because the distribution of
      neurochemicals within the frog brainstem is similar to that of amniotes, our
      results emphasize the large amount of conservation of structure, biochemistry,
      and possibly function that has occurred in the brainstem, and especially in the
      phylogenetically old reticular formation.

PMID- 11514980
TI  - Free-floating cryostat sections for immunoelectron microscopy: Bridging the gap
      from light to electron microscopy.
AB  - Frozen skin sections are routinely used for light microscopic immunohistochemical
      study of the skin basement membrane zone for two reasons: some skin basement
      membrane zone proteins are labile to routine chemical fixation, and skin is not
      amenable to vibratome sectioning. However, inherent limitations of conventional
      frozen sections, including compromised morphology and a requirement for glass
      slide-mounting, usually limit immunohistochemical study to the light microscopy
      level. In the present study, we introduce use of unfixed, free-floating cryostat
      sections for characterization of immunolocalizations of selected skin basement
      membrane proteins at both the light and electron microscopy level. The new
      procedure employs free-floating cryostat sections that can be processed as
      routine tissue specimens and can be subjected to a variety of special staining
      procedures including immunohistochemistry. Especially useful is the ease of
      progressive processing of the same tissue specimen from light microscopy to
      electron microscopy. In this regard, the method renders itself useful when
      results of immunolabeling experiments need to be elucidated quickly at
      histological and ultrastructural levels as required for diagnostic and
      accelerated investigative strategies.

PMID- 11514981
TI  - Cytochemical study of Streptococcus agalactiae and macrophage interaction.
AB  - Light and electron microscopy were used to analyse the process of interaction of
      Streptococcus agalactiae (serotypes Ia, III, and V) with resident and activated
      mouse peritoneal macrophages. Transmission electron microscopy showed that
      adherence of the S. agalactiae serotype Ia, but not III and V serotypes, to the
      surface of activated macrophages triggers the respiratory oxidative burst as
      revealed by the presence of reduced nicotinamide adenine dinucleotide (phosphate)
      [NAD(P)H]-oxidase in the phagocytic vacuoles. Fusion of macrophage lysosomes with
      bacteria-containing phagocytic vacuoles was observed in macrophages treated with
      Lucifer yellow as well as by localization of acid phosphatase for all serotypes.

PMID- 11514982
TI  - Integrated approach for segmentation of 3-D confocal images of a tissue specimen.
AB  - In this article we have proposed an integrated approach for segmentation of cells
      in volumetric image data obtained using the Confocal Microscope. The volumetric
      images are the stack of two-dimensional (2-D) images. Segmentation of cells in
      such an image stack is a difficult problem due to the complex structure of the
      objects and the spatial relationship of the object signatures in different image
      slices of the image stack. Here we have proposed a segmentation technique, which
      is a combination of several known and novel segmentation methods. Low-level
      techniques such as edge operators, middle-level techniques such as 3-D watershed,
      rule-based merging, and a high level technique, active surface model
      optimization, are integrated in one approach to get better segmentation with less
      human interaction. Some image enhancement and noise reduction techniques are also
      used to reduce the error in intermediate stages and speed up the segmentation
      process. Results are shown on 3-D images of prostate cancer tissue specimen.

PMID- 11514984
TI  - Nervous system-derived chondroitin sulfate proteoglycans regulate growth cone
      morphology and inhibit neurite outgrowth: a light, epifluorescence, and electron
      microscopy study.
AB  - Proteoglycans influence aging and plasticity in the nervous system. Particularly
      prominent are the chondroitin sulfate proteoglycans (CSPGs), which are generally
      inhibitory to neurite outgrowth. During development, CSPGs facilitate normal
      guidance, but following nervous system injury and in diseases of aging (e.g.,
      Alzheimer's disease), they block successful regeneration, and are associated with
      axon devoid regions and degenerating nerve cells. Whereas previous studies used
      non-nervous system sources of CSPGs, this study analyzed the morphology and
      behavior of sensory (dorsal root ganglia) neurons, and a human nerve cell model
      (SH-SY5Y neuroblastoma cells) as they contacted nervous system-derived CSPGs,
      using a variety of microscopy techniques. The results of these qualitative
      analyses show that growth cones of both nerve cell types contact CSPGs via actin
      based filopodia, sample the CSPGs repeatedly without collapse, and alter their
      trajectory to avoid nervous system-derived CSPGs. Turning and branching are
      correlated with increased filopodial sampling, and are common to both neurons and
      Schwann cells. We show that CSPG expression by rat CNS astrocytes in culture is
      correlated with sensory neuron avoidance. Further, we show for the first time the
      ultrastructure of sensory growth cones at a CSPG-laminin border and reveal
      details of growth cone and neurite organization at this choice point. This type
      of detailed analysis of the response of growth cones to nervous system-derived
      CSPGs may lead to an understanding of CSPG function following injury and in
      diseases of aging, where CSPGs are likely to contribute to aberrant neurite
      outgrowth, failed or reduced synaptic connectivity, and/or ineffective
      plasticity.

PMID- 11514985
TI  - Evidence for target-specific outgrowth from subpopulations of grafted human
      dopamine neurons.
AB  - Clinical and experimental grafting in Parkinson's disease has shown the need for
      enhanced survival of dopamine neurons to obtain improved functional recovery. In
      addition, it has been suggested that a limited number of surviving dopamine
      neurons project to the dopamine-denervated host striatum. The aim of this study
      was to investigate if subpopulations of ventral mesencephalic dopamine neurons
      project to their normal targets, i.e., dorsal vs. ventral striatum. Following
      implantation of human ventral mesencepahlic tissue into the lateral ventricle of
      dopamine-depleted rats, human-derived dopamine reinnervation was achieved both in
      dorsal and ventral striatum. Treatment with the neurotoxin 1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine (MPTP) resulted in a degeneration of tyrosine
      hydroxylase (TH)-immunoreactive nerve fibers in dorsal striatum but not in
      ventral areas in some animals, while MPTP was without effect in other animals. TH
      immunoreactive neurons were small and appeared shrunken in animals carrying
      grafts affected by the MPTP treatment. In conclusion, grafted dopamine neurons
      projected nerve fibers into areas that they normally innervate. Thus, when
      searching for factors that may enhance survival of grafted dopamine neurons it is
      important to study which subpopulation(s) of ventral mesencephalic dopamine
      neurons is affected, such that a proper reinnervation may be achieved.

PMID- 11514986
TI  - Effects of age and GDNF on noradrenergic innervation of the hippocampal
      formation: studies from intraocular grafts.
AB  - Recent studies have suggested that factors in the target tissue influence the
      degree of plasticity and regeneration following aging and/or specific insults. We
      have investigated whether young or aged targets differ in their noradrenergic
      innervation from fetal locus coeruleus (LC) neurons, and also if a specific
      growth factor, glial cell line-derived neurotrophic factor (GDNF) can affect this
      innervation pattern. Tissue pieces of fetal brainstem and young (3 months) or old
      (18 months) iris tissue were transplanted simultaneously into the anterior
      chamber of the eye of adult hosts. We found that aged iris transplants became
      innervated to a significantly lesser degree by the cografted LC neurons than
      young iris transplants. Fetal hippocampal tissue was then grafted to adult hosts,
      and a fetal brainstem graft containing LC neurons was placed adjacent to the
      first graft, either at 3 or 21 months post-grafting. Thus, old/young chimeras of
      the noradrenergic coeruleo-hippocampal pathway were created. Aged hippocampal
      grafts received a much less dense innervation from co-grafted LC neurons than
      young hippocampal grafts. Tyrosine hydroxylase-positive-immunoreactive
      innervation was only found in the outskirts of aged grafts, while the young
      hippocampal grafts contained an even innervation pattern. The innervation density
      of hippocampal grafts was significantly enhanced by GDNF treatment. These
      findings demonstrate that target-derived factors may regulate neuronal
      plasticity, and that the age of the target is more important for innervation
      properties than the age of the neuron innervating a particular target.

PMID- 11514987
TI  - GDNF improves cerebellar Purkinje neuron function in aged F344 rats.
AB  - Aging is associated with a decline in the function of beta-adrenergic receptor
      responses in the cerebellum. This decline in noradrenergic receptor sensitivity
      may underlie some of the accompanying age-related declines in motoric learning
      behaviors. Glial cell line-derived neurotrophic factor (GDNF) has been reported
      to prevent the degeneration of noradrenergic neurons following neurotoxic
      lesions. Thus, it was of interest to examine if GDNF would have a beneficial
      effect on age-related declines in noradrenergic function. Eighteen-month-old F344
      rats were injected with 500 microg GDNF in 20 microl into the cisterna magna.
      Three weeks following GDNF or vehicle treatment, rats were tested on a motor
      coordination task and then examined electrophysiologically under urethane
      anesthesia. GDNF did not produce an improvement in performance on an inclined
      balance beam or an accelerating rotorod. In young (3-month-old) F344 rats
      isoproterenol (ISO) will increase GABAergic inhibitions in the majority of cells
      examined; however, in aged rats only about 30% of neurons demonstrate this
      phenotype. In the aged rats treated with GDNF, ISO was able to increase GABAergic
      inhibitions in greater than 75% of the neurons tested, thus returning the neurons
      to a young phenotype. We examined the brains for expression of bcl-2, which has
      been shown to be increased in the aged cerebellum. GDNF was able to down-regulate
      this neuronal signal. Thus, intra-cisterna magna delivery of GDNF to aged rats
      improved beta-adrenergic receptor function and reduced stress related signaling
      of bcl-2 in the aged F344 rats to a level similar to that observed in young rats.

PMID- 11514988
TI  - Chronic intrathecal infusions after spinal cord injury cause scarring and
      compression.
AB  - Intrathecal infusions are used in a number of rodent studies to deliver
      substances to the injured spinal cord. Whereas this method has been successful in
      certain paradigms, two potential limitations of this model have not been
      extensively reported: (1) scar formation at the catheter tip, which can lead to
      infusion failure, and (2) damage to the spinal cord caused by the catheter
      itself. Thus, the purpose of the present study was threefold: (1) to determine
      intrathecal infusion efficiency over 14 days following spinal cord injury; (2) to
      examine possible secondary damage caused by intrathecal tubing; and (3) to
      explore whether alternative protocols that avoid such damage are effective. Adult
      Fischer 344 rats were subjected to spinal cord lesions at T7, followed by
      placement of an intrathecal catheter attached to an Alzet minipump. Seven or 14
      days following injury and catheter placement, tube patency was evaluated by
      diffusion of Evans Blue dye from the minipump. Results indicate that infusion was
      efficient 7 days following injury but was markedly reduced after 14 days.
      Further, histology and immunocytochemistry 14 days after injury demonstrated
      compression damage to the cord where the tubing rested. Alternative protocols,
      including intrathecal infusions through metal cannulae, or "drip" infusions
      directly over the lesion, did not improve delivery. These data suggest that
      results from rodent studies using infusion from catheters placed adjacent to
      lesion sites may be attributable to acute or subacute effects of the delivered
      substance. Future rodent studies using intrathecal infusions should include
      rigorous evaluation of infusion efficiency and possible secondary tissue damage.

PMID- 11514989
TI  - Early clinical experience with the 6 French Angio-Seal device: immediate closure
      of femoral puncture sites after diagnostic and interventional coronary
      procedures.
AB  - The objective of this study was to assess the early safety and efficacy of the
      novel 6 Fr Angio-Seal device for routine clinical use after diagnostic cardiac
      catheterization and coronary angioplasty. In a prospective study, we used the 6
      Fr Angio-Seal device in 180 consecutive patients (131 male, 49 female, mean age
      60.7 years) for closure of femoral arterial puncture sites immediately after
      diagnostic (n = 108) or interventional (n = 72) coronary procedures independent
      of the coagulation status. All patients were monitored for 24 hr after the
      procedure and followed for 30 days. The closure device was successfully deployed
      in 95.4% after diagnostic catheterization versus 98.6% after coronary angioplasty
      (P = 0.963). Immediate hemostasis was achieved in 91.5% versus 90.1% of the
      patients (P = 0.993). Major complications were observed 1.9% versus 2.8% of the
      patients (P = 0.885). During 30-day follow-up, no late events or complications
      were reported. The 6 Fr Angio-Seal device is a safe and effective device that
      allows for immediate closure of femoral puncture sites after both diagnostic and
      interventional procedures with a low rate of major complications.

PMID- 11514990
TI  - It's time to seal every artery but... comparing apples and oranges in the
      vascular sealing literature.

PMID- 11514991
TI  - Use of a percutaneous arterial suture device (Perclose) in patients undergoing
      percutaneous balloon aortic valvuloplasty.
AB  - Percutaneous balloon aortic valvuloplasty has been used as a therapeutic option
      for patients with severe aortic stenosis who are not candidates for aortic valve
      replacement. This procedure has been limited by both the high rate of aortic
      valve restenosis and high procedural morbidity related chiefly to the large
      femoral arteriotomies required. The purpose of this study was to assess the
      feasibility and vascular complication rate using the "Preclose" technique in
      patients undergoing balloon aortic valvuloplasty. We evaluated the immediate and
      30-day results in 18 consecutive patients undergoing this procedure.
      Angiographically significant peripheral vascular disease was present in 39% of
      cases. Aortic balloon dilation produced significant decreases in the mean aortic
      valve pressure gradient from 55 +/- 20 mmHg to 30 +/- 22 mmHg (P < 0.001).
      Closure of the arteriotomy with an 8F (10F in 1 case) Perclose device led to
      immediate hemostasis in all patients. Perclose of the contralateral femoral
      arterial site with a 6F device was attempted in 50%, all of which were
      successful. The mean length of bed rest was 4.5 +/- 0.9 hr. No procedural was
      observed. No patient had a local vascular complication, and no patient required
      blood product transfusion after the procedure. The use of the "Preclose"
      technique for closure of femoral arteriotomies after balloon aortic valvuloplasty
      is feasible and associated with a low rate of periprocedural and short-term
      vascular complications.

PMID- 11514992
TI  - Femoral arterial preclosure: finishing a procedure before it begins.

PMID- 11514993
TI  - Reproducibility of intravascular ultrasound and intracoronary Doppler
      measurements.
AB  - The aim of this study was to evaluate the reproducibility of intravascular
      ultrasound (IVUS) and intracoronary (IC) Doppler flow velocity measurements. The
      use of IVUS and IC Doppler has been suggested as a means for percutaneous
      coronary intervention (PCI) guidance in a series of studies. This would require
      an acceptable level of accuracy and reproducibility of these two methods for
      lesion evaluation. In this study, the main focus was on the issue of
      reproducibility. One hundred and eight patients referred for PCI entered into the
      study. Inter- and intraobserver variability was measured. Catheter difference was
      assessed. On-line and off-line measurements were compared. MUSIC criteria were
      assessed off-line, twice. Calculated and measured diameters were compared. After
      having obtained initial IC Doppler measurements, the Doppler wire was immediately
      withdrawn and repositioned for reacquisition of Doppler measurements. IVUS
      measurements are reproducible and reliable off-line and, to a slightly lesser
      degree, on-line. Area measurements should be performed more than once and the
      mean used for vessel description. Lumen diameters should be calculated from the
      mean of the area measurements. A measuring technique consensus should be reached
      and adhered to. CFR measurements can be used to determine reduced vs. normal flow
      reserve. In this study, it was found that proximal to distal velocity ratio and
      diastolic to systolic velocity ratio variability made these parameters unsuitable
      for PCI guidance.

PMID- 11514994
TI  - Assessing coronary blood flow dynamics with the TIMI frame count method:
      comparison with simultaneous intracoronary Doppler and ultrasound.
AB  - This study compared the TIMI frame count (TFC), which has been proposed as a
      method for quantifying coronary blood flow, with coronary flow and microvascular
      function measured with intracoronary Doppler and intracoronary ultrasound.
      Coronary blood flow volume was calculated from coronary blood velocity (by
      intracoronary Doppler) and lumen area (by intracoronary ultrasound) in the LAD in
      46 post-heart transplant patients at baseline and after intracoronary adenosine.
      TFC correlated significantly with average peak coronary blood velocity (r = 
      0.42; P = 0.004) and coronary lumen area (r = 0.39; P = 0.008), but not with
      coronary blood flow volume (r = -0.01; P = 0.96) or the coronary flow reserve
      response to adenosine (r = 0.09; P = 0.58). In conclusion, TFC is a simple method
      of assessing coronary blood velocity but not volumetric flow. While TFC does not
      predict coronary flow reserve, as a measure of velocity it does provide an
      assessment of basal microvascular tone, information that is complementary to that
      afforded by flow reserve measurements.

PMID- 11514995
TI  - Direct coronary stenting: effect on coronary blood flow, immediate and late
      clinical results.
AB  - Direct stenting (DS) was attempted in 99 coronary lesions in 94 patients while
      standard stenting (SS) was attempted in 113 lesions in 103 patients matched for
      clinical characteristics, stenosis type, and location and stent type. The
      angiographic result was also evaluated according to TIMI frame count method (TFC)
      before and after procedure. A clinical follow-up was performed 1 year after the
      procedure. Before the procedure, TIMI grade 3 flow was detected in 42 cases
      (42.4%), grade 2 in 40 cases (40.4%), grade 1 in 5 cases (5.1%), and grade 0 in
      12 cases (12.1%) in the DS group; these data were similar in SS group. After the
      procedure, TIMI grade flow was 3 in 90 cases (92.8%) in DS group and in 87
      (77.0%) in SS group (P < 0.005); grade 2 was observed in 7 case (7.2%) in DS
      group and in 25 (22.1%) in SS group (P < 0.005). Major adverse cardiac events
      during hospitalization and at follow-up were similar in two groups. Radiation
      exposure time and procedure costs per lesion were significantly reduced in DS
      group compared to SS group (10.1 +/- 8 min vs. 13.9 +/- 4.7 min, P < 0.001; and
      1901 +/- 687 Euro vs. 2352 +/- 743 Euro, P < 0.001, respectively). This study
      confirms that, in selected patients, direct stenting is a safe and successful
      procedure, allowing a significant reduction in radiation exposure time and
      procedural costs compared to standard stenting technique. The angiographic
      success is confirmed by the improvement in TFC in all cases.

PMID- 11514998
TI  - Initial results of the Quanam drug eluting stent (QuaDS-QP-2) Registry (BARDDS)
      in human subjects.
AB  - Thirty-two patients presenting with varied coronary syndromes and anatomy were
      treated with a new coronary multisleeve drug delivery coronary stent (QuaDS-QP-2)
      containing up to 4,000 microg of a taxol-derived lipophilic microtubule inhibitor
      (QP2). The device was successfully implanted in 32 patients who have been
      followed for up to 2 years. Twenty-five patients have undergone stress ECHO or
      SPECT Thallium and all are currently asymptomatic. Thirteen patients have already
      been restudied angiographically, by IVUS and/or by SPECT Thallium testing and are
      detailed in this report. Angiographic, IVUS, and SPECT Thallium have been
      controlled at a mean of 11.2 months (range, 6-15 months) in this 13-patient
      cohort. Although all 13 QuaDS-QP-2 (QDES) stents were angiographically and IVUS
      patent, two reinterventions have been required in the 32-patient study group thus
      far, both relate to either new disease or to distal, small-vessel disease beyond
      the stent. There was no evidence of significant proliferation in the QDES
      devices. On the basis of this preliminary data and a European pilot study, a
      controlled randomized trial (SCORE) is currently in progress in western Europe.

PMID- 11514996
TI  - Overestimation of stent delivery balloon diameters by manufacturers' compliance
      tables: a quantitative coronary analysis of Duet and NIR stent implantation.
AB  - Although manufacturers' compliance tables of stent delivery balloons indicate the
      diameter of the balloon at a given inflation pressure, it is unclear whether
      these data correlate with in vivo true intracoronary balloon diameters (TBDs).
      The TBDs of two new-generation balloon-expandable stent delivery systems (Duet
      and NIR) were measured by quantitative coronary analysis (QCA) in 100 consecutive
      patients. The manufacturers' stated balloon diameter (BD) of the stent delivery
      systems overestimated the TBD in 94% +/- 4% of patients receiving both Duet or
      NIR stent implantations. In only 6% of the patients, the TBD matched the
      manufacturers' stated balloon diameter. There was no underestimation of TBDs by
      both manufacturers' compliance tables. The Duet tables overestimated TBDs by 14%
      +/- 8% (range, 1%-36%), the NIR tables by 18% +/- 8% (range, 1%-41%), P < 0.05,
      Duet vs. NIR, respectively. When the manufacturers' data were corrected for the
      differences in reporting data from in vitro tests, i.e., balloon compliance data
      with or without the stent, the degree of overestimation of diameters was similar
      for Duet and NIR stent delivery balloons (14% +/- 8% vs. 13% +/- 7%, Duet vs.
      NIR; P = NS). Manufacturers' compliance tables of both the Duet and NIR stent
      delivery balloon systems significantly overestimate the true intracoronary
      balloon diameter. The manufacturers' of stent delivery balloons should clearly
      state on the box, if balloon compliance data were derived from in vitro bench
      testing, which phantoms were used for compliance analysis, and that the tables
      may overestimate the true intracoronary balloon diameter. The findings of the
      present study have important clinical implications with respect to performing
      coronary stent implantation with precision.

PMID- 11514999
TI  - Thrombolytic therapy for acute myocardial infarction.

PMID- 11515000
TI  - Use of the new IntraStent for treatment of transverse arch hypoplasia/coarctation
      of the aorta.
AB  - We report the use of a new biliary stent (IntraStent Double Strut LD) adapted for
      use in a 16-year-old young man with moderate-severe transverse arch
      hypoplasia/coarctation of the aorta following two surgical attempts at
      correction/relief of the coarctation. The stent implantation procedure resulted
      in complete relief of the coarctation.

PMID- 11515001
TI  - Recanalization and thrombectomy of internal anastomosis in a patient with
      tetralogy of Fallot using the AngioJet rheolytic catheter.
AB  - The modified Blalock-Taussig shunt is the palliative treatment of choice for
      tetralogy of Fallot. Shunt thrombosis is a potential complication, requiring high
      risk reoperation. The use of percutaneous rheolytic devices for thrombus removal
      in such occluded shunts has not been previously reported. We describe a case in
      which use of a rheolytic catheter resulted in significant thrombus removal and
      rapid reversal of cyanosis and dyspnea in a 5-year-old patient. The patient
      remains free of symptoms at 30-day follow-up.

PMID- 11515002
TI  - Transcatheter closure of a posttraumatic ventricular septal defect with an
      Amplatzer occluder device.
AB  - Cardiac traumatization may lead to severe complications. Transcatheter closure of
      a postraumatic ventricular septal defect (VSD) was successfully done using an
      Amplatzer septal occluder in a man who had previously undergone surgery for
      myocardial fissure and mitral valve dysfunction. In selected cases, the
      percutaneous approach may be a valuable option to close muscular VSDs.

PMID- 11515003
TI  - Excimer laser facilitated percutaneous coronary intervention of a nondilatable
      coronary stent.
AB  - A patient is described in which excimer laser percutaneous coronary intervention
      is performed inside a suboptimally expanded stent due to nondilatable calcified
      plaque. The use of excimer laser facilitated full expansion of the stent with a
      balloon.

PMID- 11515005
TI  - Safety of magnetic resonance imaging immediately following Palmaz stent implant:
      a report of three cases.
AB  - Magnetic resonance imaging (MRI) can provide important information on patients
      with congenital heart defects. There is some reluctance to perform MRI acutely
      following intravascular stent implant, due to concerns of distortion or movement
      of the stent in the magnetic field. We report on three patients who underwent MRI
      evaluation less than 14 days following Palmaz stent implant in the pulmonary
      arteries and superior vena cava, with no acute adverse outcome or long-term
      problems.

PMID- 11515006
TI  - Percutaneous transluminal alcohol septal myocardial ablation after aortic valve
      replacement.
AB  - When left ventricular outflow tract obstruction develops after aortic valve
      replacement, few treatment choices have been available until now. We present a
      patient with prior aortic valve replacement who developed left ventricle outflow
      tract obstruction that was successfully treated with a percutaneous transcoronary
      myocardial septal alcohol ablation. This technique is a useful tool for the
      treatment of obstructive hypertrophic cardiomyopathy, especially in those
      patients with prior heart surgery.

PMID- 11515007
TI  - Intravascular ultrasound diagnosis of cystic adventitial degeneration of the
      popliteal artery: a case report.
AB  - The diagnosis of cystic adventitial degeneration (CAD) is difficult. We present
      the first case in which intravascular ultrasound (IVUS) correctly identified CAD
      of the popliteal artery when duplex sonography and angiography were inconclusive.

PMID- 11515008
TI  - Brachytherapy for in-stent restenosis through the internal mammary artery.
AB  - We report five cases treated with brachytherapy through the internal mammary
      artery (IMA) for in-stent restenosis at the distal anastomosis (n = 3) and in the
      left anterior descending coronary artery beyond the distal anastomosis (n = 2).
      After angioplasty, catheter-based gamma radiation was performed. There was no
      delivery failure of the radiation system. All cases had angiographic success and
      no procedural or in-hospital complications.

PMID- 11515009
TI  - Percutaneous recanalization and balloon angioplasty of congenital isolated local
      atresia of the aortic isthmus in adults.
AB  - Congenital isolated local atresia of the aortic isthmus is anatomically similar
      and morphogenetically related to congenital coarctation of the aorta and was
      encountered in 4 out of 26 consecutive adult patients selected for coarctation
      angioplasty at our center. Anterograde recanalization of the atresia was safely
      and successfully accomplished in all four patients, using a brachial approach.
      Balloon dilation in the four patients, with ancillary stent implantation in one
      patient, resulted in reduction of translesion gradient from 84 +/- 11 mm Hg to 9
      +/- 7 mm Hg without complications. Angiography in the three non-stented patients
      after a mean follow-up of 13 months showed no evidence of restenosis, dissection
      or aneurysm formation, though one patient had mild dilatation of the posterior
      aspect of the aortic isthmus. The clinical presentation of patients with isolated
      local aortic atresia, and their short- to mid-term response to percutaneous
      treatment, is similar to that of patients with isolated severe coarctation of
      aorta.

PMID- 11515010
TI  - Acute symptomatic hyponatremia complicating invasive cardiac procedures: a report
      of three patients.
AB  - Hyponatremic encephalopathy is a well-known complication of surgical procedures.
      This syndrome has not been described in the cardiology literature. We report
      three patients who developed acute hyponatremia with life-threatening
      encephalopathy following an invasive cardiac procedure. Diagnosis and treatment
      were delayed because of a lack of awareness for the syndrome among the cardiology
      staff. The diagnosis of hyponatremia should be suspected in any patient who
      develops behavioral or neurological manifestations following an invasive cardiac
      procedure. Prompt diagnosis and treatment are essential to avoid permanent
      neurological damage or death.

PMID- 11515011
TI  - Intra-aortic counterpulsation during carotid stenting.
AB  - Postprocedural hypotension following endovascular stent placement of carotid
      artery disease (CAS) predicts increased in-hospital complications and long-term
      risk of death. Intra-aortic balloon counterpulsation (IABP) both increases mean
      arterial pressure and cerebral blood flow and therefore possibly reduces
      complications due to hemodynamic instability during and after CAS. In this study,
      we describe the use of IABP in a patient with severe depression of left
      ventricular function due to diffuse coronary artery disease undergoing CAS.
      Controlled studies are necessary to demonstrate a potentially protective role of
      IABP in high-risk CAS patients.

PMID- 11515012
TI  - Coil embolization for successful treatment of perforation of chronically occluded
      proximal coronary artery.
AB  - We describe a case of a coronary artery perforation involving the proximal right
      coronary artery that was successfully managed by percutaneous coil embolization.
      In the setting of a chronic coronary artery occlusion, this demonstrates the
      successful use of thrombogenic platinum alloy coils for a large proximal vessel
      perforation which has not been described previously.

PMID- 11515013
TI  - Hemodynamic rounds: Transvalvular pressure gradient measurement.

PMID- 11515014
TI  - Local delivery of paclitaxel using the double-balloon perfusion catheter before
      stenting in the porcine coronary artery.
AB  - Paclitaxel is a new cancer chemotherapeutic agent that has been approved for
      clinical use in patients with a variety of different cancers. Paclitaxel inhibits
      cell proliferation by an action on microtubules. The aim of this study was to
      evaluate the safety and efficacy of locally delivered paclitaxel after coronary
      stent implantation. A novel double-balloon perfusion catheter was used to deliver
      the drug locally in the pig coronary artery. Twenty-seven domestic pigs underwent
      stent implantation of the left anterior descending artery. In the treatment group
      (n = 11), paclitaxel (10 ml; 10 micromol/l) was delivered using the double
      balloon perfusion catheter prior to stent implantation. The control group
      received stent implantation only (n = 16). The animals were sacrificed 4 weeks
      later. Vessels were perfusion-fixed and morphometric analysis was performed using
      conventional techniques. In addition, the extent of injury was determined at each
      stent-strut area. Correlation of local injury and neointimal thickness was
      evaluated by linear regression. Neointimal thickness (paclitaxel 1.0 +/- 0.4 vs.
      control 0.7 +/- 0.3 mm), neointimal area (paclitaxel 4.1 +/- 2.2 vs. control 2.4
      +/- 1.1 mm(2)), and the lumen area (paclitaxel 2.1 +/- 1.9 vs. control 2.5 +/-
      0.9 mm(2)) did not show significant differences between both groups. Medial area
      (3.3 +/- 2.3 vs. 1.6 +/- 0.4 mm(2)) was larger in the vessels treated with
      paclitaxel (P < 0.05). Linear regression failed to show any difference in the
      response to injury between the two groups. Local delivery of paclitaxel with the
      double-balloon-perfusion catheter did not reduce neointima formation following
      stent implantation in native pig coronary arteries.

PMID- 11515015
TI  - The messenger and the message: Preventing restenosis.

PMID- 11515016
TI  - Experimental evaluation of a modified Amplatzer duct occluder.
AB  - The purpose of this study was to evaluate a new device specifically designed for
      patent ductus arteriosus (PDA) occlusion based on PDA anatomy. Percutaneous
      closure of aortopulmonary shunts was attempted in 10 dogs. Shunts were surgically
      created in the location and orientation of PDA. The occlusion prosthesis
      consisted of a cylindrical frame filled with polyester and a 32 degree angled
      retention disk. The delivery system of the device included a 6 Fr thin-walled
      Teflon introducing sheath, an antirotating delivery catheter, and cable. Complete
      occlusion of the shunt was obtained in nine animals. One animal died before
      device placement. Temporary hemolysis occurred in one dog after device placement.
      The disk of device was completely covered by smooth glistening neoendothelium at
      1-3 months postmortem examination. None of the devices protruded into the lumen
      of the aorta. The device is an improvement over the standard Amplatzer duct
      occluder. The angled retention disk lies flatly against the aortic wall, avoiding
      turbulence or an aortic pressure gradient.

PMID- 11515017
TI  - Spontaneous coronary artery dissection.

PMID- 11515019
TI  - Immunosuppression and carcinogenesis: contrasting effects with 7,12
      dimethylbenz[a]anthracene, benz[a]pyrene, and 3-methylcholanthrene.

PMID- 11515020
TI  - Effect of infection with Moloney sarcoma and leukemia viruses on nucleic acid
      synthesis in mouse cell cultures.

PMID- 11515021
TI  - Inhibition of transplanted rat tumors by immunization with identical tumor cells
      infected with Friend virus.

PMID- 11515022
TI  - Action of cytotoxic agents on the erythroid system of the mouse.

PMID- 11515023
TI  - Induction of fibrosarcomas in rabbits by polyoma virus.

PMID- 11515024
TI  - Studies on the relation of membrane immunofluorescence to Epstein-Barr virus
      infection.

PMID- 11515025
TI  - Evaluation of the effect of remission plasma on untreated patients with Burkitt's
      lymphoma.

PMID- 11515026
TI  - Fragmentation of the nucleus in Rous sarcoma virus-infected chick embryo cells.
      II. Structural and metabolic studies.

PMID- 11515027
TI  - Combined effects of 3-methylcholanthrene, mammary tumor virus, nodule-inducing
      virus, and prolonged hormonal stimulation on the tumor-producing capabilities of
      the nodule outgrowth line D1.

PMID- 11515028
TI  - Tumor-producing capabilities of hyperplastic alveolar nodules in virgin and
      hormone-stimulated BALB/c f. C3H and C3Hf mice.

PMID- 11515029
TI  - Study of human rectal epithelial cells in vitro. III. RNA, protein, and DNA
      synthesis in polyps and adjacent mucosa.

PMID- 11515030
TI  - Epidemiology of bone cancer in children.

PMID- 11515031
TI  - Kinetic evaluation of the effect of hydroxyurea on viability of replicating
      cultured leukemia L1210 cells.

PMID- 11515032
TI  - Induction of hematopoietic neoplasms in miniature swine by chronic feeding of
      strontium-90.

PMID- 11515033
TI  - Pulmonary tumors in germfree mice: induction with urethan.

PMID- 11515034
TI  - Nutritional variation influence on simian virus 40-transformed human amnion cell
      strains.

PMID- 11515035
TI  - Antibodies to Epstein-Barr virus in nasopharyngeal carcinoma, other head and neck
      neoplasms, and control groups.

PMID- 11515036
TI  - Cytologic manifestations of neoplastic transformation in vitro.

PMID- 11515037
TI  - Morphological transformation of rat embryo cells induced by diethylnitrosamine
      and murine leukemia viruses.

PMID- 11515038
TI  - Lack of adaptation in lipogenesis by hepatomas 9098, 7794A, and 9618A.

PMID- 11515039
TI  - Some aspects of the role of vitamin B12 in nucleic acid synthesis in a neoplastic
      C3H mouse cell strain. I. Growth studies.

PMID- 11515040
TI  - Some aspects of the role of vitamin B12 in nucleic acid synthesis in a neoplastic
      C3H mouse cell strain. II. Incorporation of precursors.

PMID- 11515041
TI  - Determination of sex of teratomas derived from early mouse embryos.

PMID- 11515042
TI  - Some aspects of the morphology of the Bittner virus.

PMID- 11515043
TI  - Evidence for the defectiveness of the Harris strain of Rous sarcoma virus.

PMID- 11515044
TI  - Sequential morphological changes in N-methyl-N'-nitro-N-nitrosoguanidine
      carcinogenesis in the glandular stomach of rats.

PMID- 11515045
TI  - Polymer tumorigenesis: clonal determination of histopathological characteristics
      during early preneoplasia; relationships to karyotype, mouse strain, and sex.

PMID- 11515046
TI  - Effect of various types of carcinogens on the hatching of Artemia salina eggs.

PMID- 11515047
TI  - Factors modifying stem cell proliferation of myelomonocytic leukemic cells in
      vitro and in vivo.

PMID- 11515048
TI  - Relationship between immunologic maturation and viral oncogenesis in hamsters.

PMID- 11515049
TI  - Induction of cancer in mammary isografts from male donors to CBA female host
      mice.

PMID- 11515050
TI  - Reutilization of 131I-5-iodo-2'-deoxyuridine as compared to 3H-thymidine in mouse
      duodenum and mammary tumor.

PMID- 11515051
TI  - Mechanism of induction of ovarian tumors in the mouse by 7,12-dimethylbenz[alpha]
      anthracene. VII. Relative activities of parent hydrocarbon and some of its
      metabolites.

PMID- 11515052
TI  - Cloning of human hematopoietic cell lines.

PMID- 11515053
TI  - Separation of tumor cells from fibroblasts with use of discontinuous density
      gradients.

PMID- 11515054
TI  - Antibodies in human sera to soluble and viral antigens found in Burkitt lymphoma
      and other lymphoblastoid cell lines.

PMID- 11515055
TI  - p-Hydroxypropiophenone effects on azo dye-induced alterations in mouse hepatic
      cells: light and electron microscopic study.

PMID- 11515056
TI  - Influence of immunosuppression and immunorestoration on the formation of urethan
      induced lung adenomas.

PMID- 11515057
TI  - Etiologic relationship of skin tumors (skin leukosis) of chickens to Marek's
      disease.

PMID- 11515058
TI  - A virus (RMTDV) derived from chemically induced rat mammary tumors. I. Isolation
      and general characteristics.

PMID- 11515059
TI  - Experimental production of testicular teratomas in mice of strains 129, A/He, and
      their F1 hybrids.

PMID- 11515060
TI  - Relationship of selenium to cancer. I. Inhibitory effect of selenium on
      carcinogenesis.

PMID- 11515061
TI  - Investigations of survival properties of airborne murine leukemia virus.

PMID- 11515062
TI  - Hepatomas in CBA/Cb/Se mice and liver lesions in golden hamsters induced by
      hydrazine sulfate.

PMID- 11515063
TI  - Systemic transfer of tumor immunity: delayed hypersensitivity and suppression of
      tumor growth.

PMID- 11515064
TI  - Bioactivity and virions in the blood of mice with mammary tumor virus.

PMID- 11515065
TI  - Antigenic loss in a transplantable, chemically induced leukemia of C57BL/6 mice.

PMID- 11515066
TI  - Parabiosis of CBA parental and (CBA-T6T6 x C57BL)F1 mice.

PMID- 11515067
TI  - Fatal melanoma of the lower limbs and other sites: an epidemiologic study.

PMID- 11515068
TI  - Incidence of multiple primary cancers. III. Cancers of the respiratory and upper
      digestive system as multiple primary cancers.

PMID- 11515069
TI  - Medium pollution rates in cell cultures.

PMID- 11515070
TI  - Factors associated with spontaneous transformation of hamster cells in culture.

PMID- 11515071
TI  - Carcinoma and intestinal metaplasia of the stomach in Colombian migrants.

PMID- 11515072
TI  - Continuous cell culture from a highly undifferentiated mouse lymphoid neoplasm.

PMID- 11515073
TI  - Alteration of skin in gross leukemia. I. Syngeneic skin-graft rejection and tumor
      development.

PMID- 11515074
TI  - Zinc content of pancreatic tumors of islet cell origin.

PMID- 11515075
TI  - C-type virus in bone marrow cells of cats with myeloproliferative disorders.

PMID- 11515076
TI  - Incorporation of 17 beta-estradiol-6,7-3H into the anterior pituitary gland of
      rats bearing a hormone-secreting pituitary tumor.

PMID- 11515077
TI  - Transplantation technique for acceleration of carcinogenesis by benz[a]anthracene
      or 3,4,9,10-dibenzpyrene [benzo(rst)pentaphene].

PMID- 11515078
TI  - Studies on the susceptibility of C57BL/6 mice to Rauscher virus. I. Properties of
      Rauscher virus-induced C57BL/6 lymphomas.

PMID- 11515079
TI  - Effects of different schedules of dose fractionation on the oxygenation status of
      a transplantable mouse sarcoma.

PMID- 11515080
TI  - Gross and microscopic changes in the lymphoreticular system during genesis of
      malignant lymphoma induced by a single injection of methylnitrosourea in adult
      mice.

PMID- 11515081
TI  - Cell susceptibility to the cytotoxic effect of the carcinogens
      dimethylnitrosamine and N-nitrosomethylurea.

PMID- 11515082
TI  - Tissue culture assay for Moloney leukemia virus.

PMID- 11515083
TI  - Carcinogenic response of the hamster respiratory tract to single subcutaneous
      administrations of diethylnitrosamine at birth.

PMID- 11515084
TI  - Cirrhosis and carcinoma of the liver in male rats given subcutaneous carbon
      tetrachloride.

PMID- 11515085
TI  - Productive infection and morphologic alteration of human cells by a modified
      sarcoma virus.

PMID- 11515086
TI  - Depressive effect of bone marrow on the yield of 7,12-dimethylbenz[a]anthracene
      induced thymic lymphomas.

PMID- 11515087
TI  - Morphology of a disease with features of malignant lymphoma in marmosets and owl
      monkeys inoculated with Herpesvirus saimiri.

PMID- 11515088
TI  - Successful transplantation of lymphosarcoma in calves treated with antilymphocyte
      serum.

PMID- 11515089
TI  - Tumor-graft rejection in syngeneic guinea pigs: evidence for a two-step
      mechanism.

PMID- 11515090
TI  - Ultrasonic vocalization responses in genetically high- and low-emotional rats.
AB  - Tsukuba High Emotional (THE) and Tsukuba Low Emotional (TLE) strains of rats have
      been congenitally bred for use in studies of emotionality. The current study
      investigated THE and TLE strain differences in the footshock-induced ultrasonic
      vocalization responses of adult male rats. Ultrasonic vocalization response
      inducibility (ratio of rats emitting ultrasounds) and vocalization activity in
      THE rats were statistically higher than in TLE rats. We next examined the causal
      relation between the ultrasonic vocalizations and the activation of the pituitary
      adrenocortical axis in response to footshocks in these two strains of rats. Rats
      were sorted into two groups, vocalizing and non-vocalizing, after being exposed
      to the shock regimen daily for 5 successive days. Basal plasma concentrations of
      ACTH and corticosterone were not different between THE and TLE rats. After
      receiving footshocks, significant increases in plasma concentrations of ACTH and
      corticosterone were induced in both strains of rats. These increases in plasma
      concentrations of ACTH and corticosterone were significantly higher in THE than
      in TLE rats. However, in vocalizing and non-vocalizing rats of both strains, no
      statistical differences in plasma concentrations of ACTH and corticosterone were
      observed after footshocks. These findings suggest that the high emotionality of
      the adult male rats was reflected in the emission of ultrasounds, and that the
      emission of ultrasonic vocalizations might not be related to the activation of
      the pituitary-adrenocortical axis.

PMID- 11515091
TI  - Establishment of specific pathogen-free (SPF) rat colonies using gnotobiotic
      techniques.
AB  - Gnotobiotic Wistar rats were produced using gnotobiotic techniques, which were
      established in the production of a SPF mouse colony, in order to establish a
      barrier-sustained colony. One strain of Escherichia coli, 28 strains of
      Bacteriodaceae (B-strains), three strains of Lactobacillus (L-strains) and a
      chloroform-treated fecal suspension (CHF, Clostridium mixture) were prepared from
      conventional Wistar rats as the microflora source. Two groups of limited-flora
      rats, E. coli plus B-strains and E. coli plus CHF, were produced. After
      confirmation that Clostridium difficile was not detected in the CHF-inoculated
      rats, two groups of limited-flora rats were transferred to an isolator and housed
      together in a cage. These rats were then orally inoculated with L-strains. The
      gnotobiotic rats showed colonization resistance to Pseudomonas aeruginosa, and
      the number of E. coli in the feces was 10(5) to 10(6)/g. The gnotobiotic rats
      were transferred to a barrier room as a source of intestinal flora for SPF
      colonies. In the SPF rats, basic cecal flora was mainly composed of
      Bacteroidaceae, clostridia, fusiform-shaped bacteria and lactobacilli, and did
      not change over a long period. Their flora became similar to that of conventional
      rats.

PMID- 11515092
TI  - Horizontal transmission of Toxoplasma gondii in squirrel monkeys (Saimiri
      sciureus).
AB  - The possibility of horizontal transmission of T. gondii was examined in squirrel
      monkeys. After three monkeys were inoculated perorally with 1.1-2.1 x 10(3) cysts
      of the T. gondii ME49, the animals were divided into two cages and maintained
      with one normal monkey for each cage as a cagemate. Two out of the three T.
      gondii-inoculated monkeys died, and the remaining one monkey was sacrificed in a
      moribund state one week after infection because of acute toxoplasmosis. Many T.
      gondii tachyzoites were recovered from broncho-alveolar lavages and were also
      found histopathologically in the lung, liver, spleen, kidney and lymph nodes and
      impression smears of tissues from the three T. gondii-inoculated monkeys by
      Giemsa staining. Anti-T. gondii antibody was examined by immunoblot assay in
      these animals, and the antibody to T. gondii major surface membrane protein (p30)
      could be detected after the start of experiment. Furthermore, a specific band of
      T. gondii NTPase gene was observed by PCR in the liver and lung of infected and
      cagemate monkeys, and the sequence of the second PCR products obtained from the
      cagemates, which were clinically normal but gave a positive result in
      immunoblotting assay, was exactly the same as the sequence of the NTPase gene of
      T. gondii ME49. These findings suggested that transmission of T. gondii from the
      infected monkeys to cagemates occurred easily, and since many T. gondii
      tachyzoites were recovered from the bronchoalveolar lavages of the three T.
      gondii-inoculated monkeys, we suggest that aerosol infection plays an important
      role for the enzootic toxoplasmosis in colonies of squirrel monkeys.

PMID- 11515093
TI  - Prolactin levels and maternal behavior induced by ultrasonic vocalizations of the
      rat pup.
AB  - The relationship among ultrasonic vocalization (USV), prolactin and maternal
      behavior was investigated in lactating rat mothers and their pups. The lactating
      mother had a cannula inserted into the external jugular vein, and was exposed to
      USVs emitted from a pup immediately. Changes of prolactin and maternal behavior
      were determined. Prolactin increased dramatically during exposure to USVs, when
      maternal search, retrieving and nest building behavior appeared significantly.
      These results suggested that the relationship among USV, prolactin and maternal
      behavior was included in communication between lactating mother and pup.

PMID- 11515094
TI  - Comparative study on isolation calls emitted from hamster pups.
AB  - Waveforms of isolation calls emitted from hamster pups, which were Syrian
      hamsters, Djungarian hamsters, and Chinese hamsters, were compared in a basic
      study on improving reproduction by decrease of cannibalism, because it was
      reported that maternal behavior was induced by isolation calls in rodents.
      Isolation calls of hamster pups, isolated from their mother and receiving cold
      stress, were collected by Real-Time Spectrogram (RTS), and calculated to
      spectrograms and power spectra by SIGNAL. Isolation calls consisted of ultrasonic
      vocalizations (USVs) and audible vocalizations (ADVs) in each species. Waveforms
      of isolation calls emitted by the hamster pups, were shown to have several
      characteristic features. In this study, the species specificity of isolation
      calls was shown in hamster pups. It would seem that the species specificity
      originates in the differences of sensitivity to cold stress via the autonomic
      nerve in hamsters.

PMID- 11515095
TI  - Quantitative trait loci for body weight in the intercross between SM/J and A/J
      mice.
AB  - We performed a genome-wide quantitative trait locus (QTL) analysis of body weight
      at 10 weeks of age in a population of 321 intercross offspring from SM/J and A/J
      mice, progenitor strains of SMXA recombinant inbred strains. Interval mapping
      revealed two significant QTLs, Bwq3 (body weight QTL3) and Bwq4, on Chromosomes
      (Chrs) 8 and 18 respectively, and five suggestive QTLs on Chrs 2, 6, 7, 15 and
      19. Bwq3 and Bwq4 explained 6% of the phenotypic variance. The SM/J alleles at
      both QTLs increased body weight, though the SM/J mouse was smaller than the A/J
      mouse. On the other hand, four of the five suggestive QTLs detected had male
      specific effects on body weight and the remainder was female-specific. These
      suggestive QTLs explained 5-6% of the phenotypic variance and all the SM/J
      alleles decreased body weight.

PMID- 11515096
TI  - Incidence of pyometra in colony-raised beagle dogs.
AB  - Incidence of pyometra observed in our colony-raised beagle dogs over a 12-year
      period is described. Pyometra was observed in 25 female dogs of more than 4 years
      old, frequently at 8-11 years, with the average age of onset 9.36 +/- 0.38 years.
      The incidence of the disease was 15.2% of the female dogs (n = 165) more than 4
      years old. Clinical findings useful in the diagnosis of this disease included an
      excretion of pus from the cervix, rapid increase in leukocyte count, and enlarged
      uterus as revealed by radiography. The relationships of delivery, estrus cycles
      to this disease are discussed. Ovariohysterectomy or uterectomy was the only
      effective method of treatment. In conclusion, the results indicated that pyometra
      might be an age-related disease because it occurred particularly in aged dogs.

PMID- 11515097
TI  - Behaviors of mice given forced-swimming.
AB  - Behaviors of mice in the forced swimming test are motionlessness, climbing and
      the other stereotypical behaviors. We observed these behaviors in different ages
      and sex and in repeated forced swimming trials. The findings were 1) quantities
      of the climbing and the other behaviors were different with the age and sex, 2)
      repeated per day forced swimming remarkably increased motionlessness and
      motionlessness is memorized for at least 14 days, and 3) climbing is the typical
      opposite behavior of motionlessness and was related to adrenergic but not
      serotonergic neuronal activity. When these behaviors are recognized as adaptation
      behaviors, we conclude that mice given repeated forced swimming, but not mice
      given one trial of forced swimming, can be considered as a model of human
      depression relating to adrenaline neuronal activity.

PMID- 11515098
TI  - Genetic association between low expression phenotype of CD62L (L-selectin) in
      peripheral CD4+ T cells and the thid (T-helper immunodeficiency) phenotype in the
      LEC rat.
AB  - Genetic linkage analysis was performed between the low expression phenotype of
      peripheral CD4+ T cells and the thid (T-helper immunodeficiency) phenotype using
      (BN x LEC)F1 x LEC backcross progenies. In contrast to a previous result using a
      thid congenic strain that the low expression phenotype of CD62L was not
      correlated with the thid phenotype, our result in this study indicated that the
      low expression phenotype of CD62L was genetically linked with the thid phenotype.
      The discrepancy between the previous and present results may be due to the source
      of animals, congenic strain versus backcross progenies. It is suggested by this
      study that the thid locus controls the expression level of CD62L in peripheral
      CD4+ T cells.

PMID- 11515099
TI  - A primary retroperitoneal seminoma invading the kidneys of a cryptorchid dog.
AB  - The relationship between cryptorchidism and testicular tumors has been well
      established in canines, and the tumor has been proposed as a model for studying
      its human counterparts. Herein we report canine malignant retroperitoneal
      seminoma in a 4-year-old castrated Basset hound, most likely without testicular
      involvement, similar to that of the classic seminoma of humans.

PMID- 11515100
TI  - Detection of B virus infection in cynomolgus monkeys by ELISA using simian agent
      8 as alternative antigen.
AB  - The use of simian agent 8 (SA8) as an antigen for B virus (BV) antibody detection
      was evaluated in cynomolgus monkeys. Seventy-two sera judged as positive using BV
      antigen were all positive when the SA8 antigen was used. Out of 28 BV-negative
      sera 2 were positive against the SA8 antigen and one serum was classified as
      indeterminate. The present data indicates that detection of BV antibody can be
      achieved accurately and safely by enzyme-linked immunosorbent assay (ELISA) using
      SA8 antigen.

PMID- 11515101
TI  - Arterial supply to the stomach of indigenous dog (Canis familiaris) in
      Bangladesh.
AB  - Arterial supply to the stomach of dogs indigenous to Bangladesh was investigated
      by using latex. The hepatic, left gastric and splenic arteries sent their major
      branches to the stomach. The cranial and caudal branches of the left gastric
      artery supplied the lesser curvature of the stomach. The right gastric, and right
      and left gastroepiploic arteries also sent their branches to both the lesser and
      greater curvatures. Six or seven short gastric arteries from the splenic artery
      supplied the greater curvature. Anastomoses between the left and right gastric,
      between the left and right gastroepiploic, and between short gastric arteries and
      left gastric arteries were observed.

PMID- 11515102
TI  - Linkage mapping of the rat 8-oxoguanine DNA glycosylase gene to chromosome 4.

PMID- 11515103
TI  - Linkage mapping of the rat interleukin 1 receptor antagonist gene on chromosome
      3.

PMID- 11515104
TI  - The insulin receptor-related receptor (Insrr) gene maps to mouse chromosome 3.

PMID- 11515105
TI  - [Medical health care services for the population under the condition of social
      differentiation].
AB  - Monitoring of availability of medical care and drugs for the population has been
      carried out by interviewing more than 4000 residents of Russian cities.
      Stratification of respondents by the level of life showed that more than 70%
      respondents evaluate their level of life as below the medium. A social gradient
      was detected: direct relationship between population morbidity and conditions of
      life. Analysis of availability of paid medical services and drugs for population
      with different level of life showed differentiation of the population by the
      level of life and by ability to pay for medical services and drugs.

PMID- 11515106
TI  - [Preterm mortality and possibility for its prevention].
AB  - The need in fundamental socio-hygienic studies aimed at solving the problem of
      preterm death prevention is validated. The attention is focussed on the health
      status of capable population of Russia and prevention of deaths caused by social
      economic crisis.

PMID- 11515107
TI  - [Age structure of mortality in Russia].
AB  - The ratios of age coefficients of mortality in Russia and European countries are
      analyzed in general and for individual causes. The role of various factors in the
      tendencies observed is demonstrated. Special attention is paid to methodological
      approaches to determination of the main cause of death. An integral approach is
      offered, which helps detect the contribution of various age groups to total
      mortality. Ranking of Russian Federation regions is offered.

PMID- 11515108
TI  - [Comprehensive evaluation of disability risk associated with diseases of
      circulation].
AB  - Diagnostic table for predicting the risk of disability for cardiovascular
      patients has been developed in order to improve expert evaluations, update the
      knowledge of physicians on new approaches to medicosocial expert evaluations of
      patients and disabled subjects, remove discoordination in clinical and expert
      activities of physicians, reduce the number of unjustified directions to bureaus
      of medicosocial expert evaluations, and timely diagnose limited vital activities
      of patients.

PMID- 11515109
TI  - [The course of physical development of children born premature].
AB  - Physical development of 474 preterm (born at 30-37 weeks) children was evaluated
      in infancy (n = 157), preschool (n = 154), and school (n = 163) age. Small-for
      date children and children corresponding to their gestation age were
      retrospectively distinguished. Control group consisted of 474 age and sex-matched
      children born after full-term gestation. Physical health status of preterm
      children of early, preschool, and school age is characterized by specific
      structural and dynamic features, qualitatively and quantitatively differing from
      the values in full-term controls. With aging, the effect of medical psychosocial
      risk factors on physical development decreases.

PMID- 11515110
TI  - [Health problems of the population of the Russian Federation and its forecasting
      up to 2005].

PMID- 11515111
TI  - [Approaches to the optimization of medical services for the population].
AB  - Describes modern approaches to optimization of medical care of the population
      under conditions of finance deficiency. Expenditure cutting is evaluated from
      viewpoint of "proof" medicine (allotting finances for concrete patients and
      services).

PMID- 11515112
TI  - [Marketing systems of public health].

PMID- 11515113
TI  - [Conceptual approaches to the organization of medico-social care of children].
AB  - Social economic crisis and decreased level of life tell on the health status of
      children. As primary health centers, pediatric outpatient clinics play the main
      role in the formation of healthy life style and rendering medicosocial care.
      However the existing system of organization of prophylactic care in pediatric
      outpatient clinics does not meet modern requirements, and problems of infant
      health care cannot be considered as purely medical. A draft program of
      restructuring local pediatric services is offered with consideration for modern
      social and economic problems.

PMID- 11515114
TI  - [Modern technologies in inpatient care].
AB  - Medical and economic efficiency of low invasive therapeutic technologies used in
      hepatobiliary and urogenital diseases is analyzed. These technologies are highly
      effective in comparison with traditional surgical methods. Their use is
      associated with a shorter hospital stay, earlier objective improvement of the
      clinical status of the majority of patients, and decreased incidence of
      complications. Use of these technologies brought about a notable economic effect.

PMID- 11515115
TI  - [Systems of measures targeted at reducing health risk factors for the
      population].
AB  - Center for State Sanitary Epidemiological Surveillance in the Samara region
      developed, tried, and introduced a system of administrative, legal, and economic
      decisions aimed at reduction of the effects of unfavorable environmental factors
      on population health. The main directions of the system is reorganization of the
      structure and administration of sociohygienic monitoring, norm-setting approach,
      organization of work in accordance with the state order, introduction of a system
      for evaluating the activities of the Center in cities and regions, optimization
      of staff, development and introduction of minimum social standards of activity,
      and realization of goal-oriented complex programs providing sanitary and
      epidemiological well-being.

PMID- 11515116
TI  - [The role of nurses in psychiatric services].
AB  - Specific features of the nursing process in practical activities of nurses of
      psychiatric service of the Russian Federation should receive special attention in
      the system of vocational training. Increase of the volume and improvement of
      quality of training, reorganization of nurses' work in an inpatient and
      outpatient setting are the main approaches to improving the quality of medical
      care and, among other things, mental health of the population.

PMID- 11515117
TI  - [Social aspects in the activities of radiodiagnostic services].
AB  - Results of sociological investigation of the staff members and patients of
      radiodiagnosis departments of treatment and prophylaxis institutions of St.
      Petersburg are analyzed. Anonymous questionnaires were distributed in 50
      institutions of different profiles among 200 staff members (physicians-
      roentgenologists and radiologists, and x-ray laboratory assistants) and 300
      patients (from x-ray rooms and radiodiagnosis departments). The study showed an
      objective picture of the state of radiological care rendered to the population
      viewed from two sides, by those rendering this care and those rendered it. The
      results helped develop recommendations for public health organization.

PMID- 11515118
TI  - [Certification of physicians at institutions of The State Sanitary
      Epidemiological Service of Moscow].

PMID- 11515119
TI  - [Organizational and methodological aspects of introducing staged clinical
      training in the educational process at the Department of Medicine at Moscow
      University].

PMID- 11515120
TI  - [The first Russian printed medical reference book].

PMID- 11515121
TI  - [The medical poster as a means of sanitary education in the 1920's].

PMID- 11515122
TI  - [Comprehensive approach to decrease of neonatal mortality].
AB  - Due to united efforts of public health at many levels neonatal mortality in
      Samara decreased from 17.3 to 7.1% during 5 years. Irish program "Positive
      Maternity" and outpatient perinatology programs helped decrease the incidence of
      severe gestosis to 15.9 per 10,000 deliveries. Services engaged in family
      planning, andrological care, and treatment of couples have been created.
      Resuscitation of newborns is realized in accordance with the Swiss Government
      Program on Maternity and Childhood Protection and the USA Protocol of Newborn
      Resuscitation. Introduction of the Placenta-Fetus-Newborn program is in progress.
      Six-year activities of a visiting neonatological team decreased neonatal
      mortality from respiratory distress syndrome almost 3-fold. Activities of Center
      for Surgical Correction of Congenital Defects are constantly updated. The rate of
      detection of congenital defects by ultrasonic examination is now as high as 75%.
      The realization of programs and activities of institutions are financed through
      obligatory medical insurance, public health budget, and purposeful programs.

PMID- 11515123
TI  - [Risk factors and measures of prevention of infant mortality].
AB  - The authors analyze endo- and exogenous factors responsible for infant death
      during the first year of life. Biological anamnesis, conditions and life style
      were studied in 102 families which had infants dead during the first year of
      life. The data were collected by interviewing mothers and analyzing primary case
      histories of infants. Statistical processing of the results of social hygienic
      study distinguished 33 significant risk factors promoting infant death. Children
      born from mothers at a high risk of perinatal disease and in socially defective
      families are at a highest risk of neonatal death. Experience gained at pediatric
      health center No. 39 in Nizhnii Novgorod is described as the optimal structure of
      a territorial pediatric health center maximally realizing the measures aimed at
      prevention of neonatal mortality. This health center has a special department for
      infants, primary prevention center, and social public health service.

PMID- 11515124
TI  - [Disability in chronic nonspecific diseases of the lungs].
AB  - The author presents the data of medical social study of disability caused by
      chronic nonspecific diseases of the lungs (CNDL) in Omsk and the Omsk region and
      analyzes the level, structure, and time course of primary disability in relation
      to sex, age, place of residence, and disability group. Working loss caused by
      CNDL in cities and in the country is evaluated. Factors promoting the formation
      of disability in CNDL are evaluated. One of important factors is the quality of
      check-ups of patients. The majority of risk factors can be controlled, which
      creates a certain reserve for decreasing disability in CNDL.

PMID- 11515125
TI  - [Prevalence of alcohol use among school children and vocational school students
      in Murmansk].
AB  - Anonymous questionnaires were distributed among 1564 schoolchildren in Murmansk
      for the study carried out in accordance with the method recommended by Center for
      Monitoring Harmful Habits among Children and Adolescents at Ministry of Health of
      Russia. The data indicate alcoholization of adolescents in the city. The results
      were used for planning and implementation of preventive measures within the
      framework of the SOS! complex regional program.

PMID- 11515126
TI  - [Socio-hygienic study of migration processes in the Belgorod region].
AB  - Relationship between migrations and marriage structure in the Belgorod region is
      studied and opinions of residents of the region on migration are investigated.
      Migration of men and women of marital age in intensely developing urbanized zones
      and in populations with different levels of urbanization is described. Residents
      of the region consider that high level of migration to the region, compensating
      for the negative natural increment and responsible for increase in the population
      exerts a negative effect on the social economic situation in the region.

PMID- 11515127
TI  - [Availability of hospital beds and indicators of the scope of medical care in day
      hospitals].
AB  - The activities of hospital-replacing forms (HRF) of medical care are analyzed for
      the Samara and Tver regions. In the Samara region the number of HRF beds was 13.2
      per 10,000 population, 9.3 of these at day-time hospitals of outpatient centers
      and 3.9 at hospitals. In the Tver region the number of day-time beds was 5.5 at
      hospitals and 0.97 at outpatient centers per 10,000 population. In the Samara
      region the estimated number of days of treatment at HRF was 475 per 1000
      population, which is sufficient.

PMID- 11515128
TI  - [Monitoring of medical activity within the framework of its complex evaluation].
AB  - The significance of high quality of initial information on medical activity as an
      object of management is emphasized. The author analyzes difficulties associated
      with obtaining necessary data and their processing for analysis. For improving
      the informative value of data on medical activity, methods of information
      obtaining based on the monitoring principle should be used. A scheme of medical
      activity monitoring, carried out for evaluating medical activity, is presented.
      The author emphasizes the necessity of high quality of initial information.

PMID- 11515129
TI  - [International cooperation in implementation of the program of reproductive
      health protection in the Samara region].
AB  - A concept of strategic development of territorial service of maternity and
      childhood protection has been developed in the Samara region making use of
      international experience. The results indicate improvement of qualitative
      parameters of the service activities after introduction of international
      programs.

PMID- 11515130
TI  - [Main trends of the population health in Russia under present-day conditions].
AB  - Decreased utilization of medical services by the population, primarily by
      economically active part of the population, under conditions of socioeconomic
      crisis is discussed as exemplified by outpatient and inpatient care and temporary
      invalidity. The direct result of decreased consultation rate is an essential part
      of diseases and abnormalities which are no longer registered in medical files and
      remain untreated, which eventually leads to development of chronic, combined,
      multiple diseases, primary disability, and untimely deaths.

PMID- 11515131
TI  - [Socioeconomic situation and population's health in the Republic of North Ossetia
      Alania in the nineties].
AB  - The economic situation for the population of North Ossetia-Alania has drastically
      deteriorated in the 90s, which primarily affected the population well-being.
      Birth rates decreased and mortality increased, because of increased number of
      suicides and murders and decrease of mean expected life-span. Results of analysis
      indicate common regularities and trends and differences between the medical
      demographic processes in North Ossetia-Alania and the entire Russian Federation;
      these common and individual features should be taken into consideration when
      organizing and planning the activity of public health system and institutions.

PMID- 11515132
TI  - [Organizational-economic aspects of the establishment of day hospitals].

PMID- 11515133
TI  - [Medical institutes at Russian universities: a special (3rd) type of higher
      medical schools in Russia in the first third of the 19th century].

PMID- 11515134
TI  - [Health status of various groups of population of workforce age].
AB  - Health status (incidence of chronic diseases, objective evaluation of the health
      status), life-style, and consultation rates were analyzed for various population
      groups.

PMID- 11515135
TI  - [Bases of socio-hygienic studies in Russia in the second half of the 19th
      century].

PMID- 11515136
TI  - [Financing of zemstvo therapeutic institutions].

PMID- 11515138
TI  - [Public health reform in the USSR in postwar years].

PMID- 11515137
TI  - [Pages from history of medical service of the Russian Navy (on the 56th
      anniversary of the victory in the Great Patriotic War)].

PMID- 11515139
TI  - [Role of P.A Stolypin in the development of public health at the beginning of the
      20th century].

PMID- 11515140
TI  - [Efrem Mukhin: surgeon, clinician].

PMID- 11515141
TI  - [Memorable dates and anniversaries in the history of public health and medicine
      in 2001].

PMID- 11515142
TI  - [Time course of demographic processes in the Astrakhan region in the nineties].
AB  - Time course of demographic processes in the Astrakhan region during economic
      reforms in Russia is analyzed. An unfavorable demographic situation consists in
      decreased number of children and increase in the number of subjects of retired
      age, a lesser number of women of reproductive age, decreased number of marriages
      and increased number of divorces. Decreased birth rate and increased mortality,
      formation of the negative natural increment in population number, and decreased
      mean duration of expected life-span. Increase in the population of the region
      from 1991 was due to newcomers, mainly from North Caucasus. The results of our
      analysis allow us to predict a decrease in the total number of population in the
      Astrakhan region for the nearest 10-15 years. Decreased number of children and
      increased number of elderly people will increase the demographic loading of
      capable population, which will inevitably lead to negative economic and
      demographic consequences.

PMID- 11515143
TI  - Dreaming and the brain: toward a cognitive neuroscience of conscious states.
AB  - Sleep researchers in different disciplines disagree about how fully dreaming can
      be explained in terms of brain physiology. Debate has focused on whether REM
      sleep dreaming is qualitatively different from nonREM (NREM) sleep and waking. A
      review of psychophysiological studies shows clear quantitative differences
      between REM and NREM mentation and between REM and waking mentation. Recent
      neuroimaging and neurophysiological studies also differentiate REM, NREM, and
      waking in features with phenomenological implications. Both evidence and theory
      suggest that there are isomorphisms between the phenomenology and the physiology
      of dreams. We present a three-dimensional model with specific examples from
      normally and abnormally changing conscious states.

PMID- 11515144
TI  - Dreaming and REM sleep are controlled by different brain mechanisms.
AB  - The paradigmatic assumption that REM sleep is the physiological equivalent of
      dreaming is in need of fundamental revision. A mounting body of evidence suggests
      that dreaming and REM sleep are dissociable states, and that dreaming is
      controlled by forebrain mechanisms. Recent neuropsychological, radiological, and
      pharmacological findings suggest that the cholinergic brain stem mechanisms that
      control the REM state can only generate the psychological phenomena of dreaming
      through the mediation of a second, probably dopaminergic, forebrain mechanism.
      The latter mechanism (and thus dreaming itself) can also be activated by a
      variety of nonREM triggers. Dreaming can be manipulated by dopamine agonists and
      antagonists with no concomitant change in REM frequency, duration, and density.
      Dreaming can also be induced by focal forebrain stimulation and by complex
      partial (forebrain) seizures during nonREM sleep, when the involvement of
      brainstem REM mechanisms is precluded. Likewise, dreaming is obliterated by focal
      lesions along a specific (probably dopaminergic) forebrain pathway, and these
      lesions do not have any appreciable effects on REM frequency, duration, and
      density. These findings suggest that the forebrain mechanism in question is the
      final common path to dreaming and that the brainstem oscillator that controls the
      REM state is just one of the many arousal triggers that can activate this
      forebrain mechanism. The "REM-on" mechanism (like its various NREM equivalents)
      therefore stands outside the dream process itself, which is mediated by an
      independent, forebrain "dream-on" mechanism.

PMID- 11515145
TI  - A review of mentation in REM and NREM sleep: "covert" REM sleep as a possible
      reconciliation of two opposing models.
AB  - Numerous studies have replicated the finding of mentation in both rapid eye
      movement (REM) and nonrapid eye movement (NREM) sleep. However, two different
      theoretical models have been proposed to account for this finding: (1) a one
      generator model, in which mentation is generated by a single set of processes
      regardless of physiological differences between REM and NREM sleep; and (2) a two
      generator model, in which qualitatively different generators produce cognitive
      activity in the two states. First, research is reviewed demonstrating
      conclusively that mentation can occur in NREM sleep; global estimates show an
      average mentation recall rate of about 50% from NREM sleep--a value that has
      increased substantially over the years. Second, nine different types of research
      on REM and NREM cognitive activity are examined for evidence supporting or
      refuting the two models. The evidence largely, but not completely, favors the two
      generator model. Finally, in a preliminary attempt to reconcile the two models,
      an alternative model is proposed that assumes the existence of covert REM sleep
      processes during NREM sleep. Such covert activity may be responsible for much of
      the dreamlike cognitive activity occurring in NREM sleep.

PMID- 11515146
TI  - The case against memory consolidation in REM sleep.
AB  - We present evidence disputing the hypothesis that memories are processed or
      consolidated in REM sleep. A review of REM deprivation (REMD) studies in animals
      shows these reports to be about equally divided in showing that REMD does, or
      does not, disrupt learning/memory. The studies supporting a relationship between
      REM sleep and memory have been strongly criticized for the confounding effects of
      very stressful REM deprivation techniques. The three major classes of
      antidepressant drugs, monoamine oxidase inhibitors (MAOIs), tricyclic
      antidepressants (TCAs), and selective serotonin reuptake inhibitors (SSRIs),
      profoundly suppress REM sleep. The MAOIs virtually abolish REM sleep, and the
      TCAs and SSRIs have been shown to produce immediate (40-85%) and sustained (30
      50%) reductions in REM sleep. Despite marked suppression of REM sleep, these
      classes of antidepressants on the whole do not disrupt learning/memory. There
      have been a few reports of patients who have survived bilateral lesions of the
      pons with few lingering complications. Although these lesions essentially
      abolished REM sleep, the patients reportedly led normal lives. Recent functional
      imaging studies in humans have revealed patterns of brain activity in REM sleep
      that are consistent with dream processes but not with memory consolidation. We
      propose that the primary function of REM sleep is to provide periodic endogenous
      stimulation to the brain which serves to maintain requisite levels of central
      nervous system (CNS) activity throughout sleep. REM is the mechanism used by the
      brain to promote recovery from sleep. We believe that the cumulative evidence
      indicates that REM sleep serves no role in the processing or consolidation of
      memory.

PMID- 11515148
TI  - [From scientific evidence to operative practice: towards a model of occupational
      medicine based on on efficacy evidence].
AB  - There is increasing interest in improving health care practice and in providing
      evidence-based health care, that is, care in which different stakeholders
      consistently consider research evidence when making decisions. Quality of health
      care is presently viewed as a goal towards which different health care settings
      are geared. In comparison with this approach and in spite of the large
      development potentialities, occupational health practice is only at the beginning
      of the process. ILO convention No. 161 already pointed out the need to provide
      customers with quality-oriented services and evidence-based services.
      Occupational health practice can be analysed by means of a general system model
      already established for health care systems including input (structure,
      management, personnel, equipment), process (activities, performance), output
      (advice, recommendation), outcome (good life quality, sickness absence, work
      ability). All these elements can be critically measured with appropriate
      indicators to evaluate their efficacy. Despite general agreement about the
      importance of such analysis, there is a lack of data on the efficacy of
      prevention programmes. According to the evidence-based medicine model, which is
      commonly used by many other medical specialties, occupational health physicians
      could adopt a similar approach in order to implement more efficacious
      interventions. The evidence-based paradigm consists in the conscientious,
      explicit and judicious use of available best evidence in making decisions about
      health care problems. The practice of evidence-based medicine means integrating
      individual expertise with the best current evidence from systematic research.
      Evidence-based occupational health should implement this innovative approach to
      evaluate and to improve the efficiency of prevention services by means of the
      ability to (i) formulate the questions on the problem; (ii) search for scientific
      evidence; (iii) critically evaluate scientific evidence; (iv) use evidence as a
      key element for the decision process.

PMID- 11515147
TI  - The reinterpretation of dreams: an evolutionary hypothesis of the function of
      dreaming.
AB  - Several theories claim that dreaming is a random by-product of REM sleep
      physiology and that it does not serve any natural function. Phenomenal dream
      content, however, is not as disorganized as such views imply. The form and
      content of dreams is not random but organized and selective: during dreaming, the
      brain constructs a complex model of the world in which certain types of elements,
      when compared to waking life, are underrepresented whereas others are over
      represented. Furthermore, dream content is consistently and powerfully modulated
      by certain types of waking experiences. On the basis of this evidence, I put
      forward the hypothesis that the biological function of dreaming is to simulate
      threatening events, and to rehearse threat perception and threat avoidance. To
      evaluate this hypothesis, we need to consider the original evolutionary context
      of dreaming and the possible traces it has left in the dream content of the
      present human population. In the ancestral environment human life was short and
      full of threats. Any behavioral advantage in dealing with highly dangerous events
      would have increased the probability of reproductive success. A dream-production
      mechanism that tends to select threatening waking events and simulate them over
      and over again in various combinations would have been valuable for the
      development and maintenance of threat-avoidance skills. Empirical evidence from
      normative dream content, children's dreams, recurrent dreams, nightmares, post
      traumatic dreams, and the dreams of hunter-gatherers indicates that our dream
      production mechanisms are in fact specialized in the simulation of threatening
      events, and thus provides support to the threat simulation hypothesis of the
      function of dreaming.

PMID- 11515149
TI  - [Significance of bronchoalveolar lavage in demonstrating previous exposure to
      asbestos].
AB  - A study was made via a clinical approach in the absence of environmental data
      with the aim of demonstrating a possible past exposure to asbestos in a working
      population that had never been examined before nor had ever undergone any
      specific health checks. It was deemed useful to compare this working population
      with a control population not exposed to asbestos. The population under study
      consisted of 126 employees of a single (thermonuclear) department of a metal
      engineering industry who reported having used asbestos as insulation material in
      all heat processes up to the beginning of the 1980's. Pleural plaques were
      observed in 13 workers that were also confirmed by high resolution TC (HRTC)
      except in one case. The control group consisted of subjects seen at the Clinica
      del Lavoro of Milan for non-asbestos related diseases in whom a fibrobronchoscopy
      with broncho-alveolar lavage (BAL) was performed for diagnostic purposes. In each
      group asbestos bodies were counted in the BAL liquid using a method with a
      detection limit of 0.1 bodies/ml. The asbestos bodies detected in the alveolar
      liquid of subjects in the control group were between a maximum of 0.25 and a
      minimum of 0 bodies/ml of liquid (mean = 0.03; SD = 0.64) whereas in the sample
      of subjects from the population under study who underwent BAL the results gave a
      concentration of asbestos bodies in the BAL liquid between a maximum of 9.0 and a
      minimum of 0.15 bodies/ml of liquid (mean = 2.38; SD = 2.72). In order to obtain
      a statistically significant difference between the control population, which was
      certainly not exposed, and the sample of subjects undergoing BAL from the
      population for which an occupational exposure was assumed, we applied the non
      parametric Wilcoxon-Mann-Whitney test for independent samples in view of the
      asymmetric distribution of the values of asbestos body concentration in the
      alveolar liquid: the result was a statistically significant difference (p <
      0.001) between the two populations. We also calculated the total asbestos bodies
      recovered in the BAL liquid of subjects from both populations. In the control
      group total asbestos bodies were between a maximum of 15 and a minimum of 0 (mean
      = 1.8; SD = 3.9) while in the group under study the concentration of total
      asbestos bodies recovered in BAL liquid was between a maximum of 990 and a
      minimum of 12.7 (mean = 206.5; SD = 270). The Wilcoxon-Mann-Whitney test was also
      applied to these data, the result of which was that the difference in exposure
      between the two populations was statistically significant (p < 0.001).
      Concluding, the study demonstrates the importance of asbestos body count in BAL
      liquid as an objective indicator of past occupational exposure to asbestos, thus
      providing documented proof that overcomes any doubts arising from case history
      and any lack of environmental data that could prove exposure.

PMID- 11515150
TI  - [Biological monitoring of occupational exposure to sevoflurane].
AB  - Sevoflurane has been used in the last few years in brief surgical operations,
      either alone or in combination with nitrous oxide. Occupationally exposed groups
      include anesthesiologists, surgeons and operating room nurses. In 1977 the
      National Institute for Occupational Safety and Health (NIOSH) recommended that
      occupational exposure to halogenated anesthetic agents (halothane, enflurane, and
      isoflurane), when used as the sole anesthetic, should be controlled so that no
      worker would be exposed to time-weighted average concentrations greater than 2
      ppm during anesthetic administration. When halogenated anesthetics are associated
      with nitrous oxide, NIOSH recommends that the limit value should not exceed 0.5
      ppm. We think these recommendations can be extended to sevoflurane. Metabolism of
      sevoflurane is catalyzed by cytochrome P-450; this involves oxidation of the
      fluoromethyl side chain of the molecule, followed by glucuronidation. Two urinary
      metabolites of sevoflurane have been identified: inorganic fluoride (which,
      however, is not specific) and a non-volatile compound that yields
      hexafluoroisopropanol (HFIP) when digested with the enzyme beta-glucuronidase. In
      order to investigate the role of urinary HFIP as an indicator of occupational
      exposure to sevoflurane (CI, ppm), CI was measured in 145 members of 18 operating
      room staffs. The measurements of the time-weighted average of CI in the breathing
      zone were made by means of diffusive personal samplers. Each sampler was exposed
      during the whole working period. Sevoflurane was desorbed with CS2 from charcoal
      and the concentrations were measured on a gas chromatograph (GC) equipped with a
      mass selective detector (MSD). The GC was equipped with a 25 meter cross-linked
      phenylmethylsilicon column (internal diameter 0.2 mm). GC conditions were as
      follows: injector column temperature = 200 degrees C; column temperature = 30
      degrees C; carrier gas = helium; injection technique of samples = splitless. The
      analytical conditions for the MSD were the following: ion mass monitored = 131
      m/e; dwell time = 50 msec; selected ion monitoring window time = 0.1 amu;
      electromultiplier = 400 V. Urine samples were collected near the end of the shift
      and were analyzed for HFIP by head-space gas chromatography after glucuronide
      hydrolysis. 0.5 ml of urine and 1.5 ml of 10 M sulfuric acid were added to 21.8
      ml headspace vials. The vials were immediately capped, vortexed, and loaded into
      the headspace autosampler. Samples were maintained at 100 degrees C for 30 min,
      after which glucuronide hydrolysis was 99% complete. Analyses were performed on a
      GC equipped with a MSD. The analytical conditions for urine analysis were as
      follows: cross-linked 5% phenylmethylsilicon column (internal diameter 0.2 mm,
      length 25 m); column temperature = 35 degrees C; carrier gas = helium. The
      analytical conditions for the MSD were: monitored ions = 51.05 and 99; dwell time
      = 100 ms; selected ion monitoring window time = 0.1 amu; electromultiplier
      voltage = 2000 Volt. With our analytical procedure, the detection limit of HFIP
      in urine was 20 micrograms/L. The variation coefficient (CV) for HFIP measurement
      in urine was 8.7% (on 10 determinations; mean value = 1000 micrograms/L). The
      median value of CI was 0.77 ppm (Geometric Standard Deviation = 4.08; range =
      0.05-27.9 ppm). The correlation between CI and HFIP (Cu, microgram/L) was: Log Cu
      (microgram/L) = 0.813 x Log CI (ppm) + 2.517 (r = 0.79, n = 145, p < 0.0001). On
      the basis of the equation it was possible to establish tentatively the biological
      limit values corresponding to the respective occupational exposure limit values
      proposed for sevoflurane. According to our experimental results, HFIP values of
      488 micrograms/L and 160 micrograms/L correspond to airborne sevoflurane
      concentrations of 2 and 0.5 ppm respectively.

PMID- 11515151
TI  - [Pleural mesothelioma in women in the Veneto Region who used to work as rag
      sorters for textile recycling and paper production].
AB  - The paper reports 9 cases of mesothelioma diagnosed by means of histology or
      cytology that were observed among women resident in the Veneto Region, Northern
      Italy, whose only activity that could involve exposure to asbestos was as rag
      sorter. These cases are part of a group of about 260 subjects with mesothelioma
      whose entire working and residential history has been collected. The women worked
      as rag sorters between the 1940's and 1960's in textile recycling (8 cases) or
      (one case) at a paper mill where cotton was used for paper production. The work
      as rag sorter helps to explain the high proportion of mesotheliomas among women
      with an occupational exposure to asbestos.

PMID- 11515153
TI  - [Occupational allergic asthma in greenhouses. Report of a clinical case].
AB  - The Authors report a particular case of occupational asthma observed in a
      greenhouse worker. They describe the diagnostic procedure followed after
      identification on the cultivated plants of colonies of aspergillus niger, a
      fungus identified as an etiologic agent of the allergic disease. The peculiarity
      of the causative agent is stressed and it is recommended that environmental and
      health prevention measures be improved for this poorly protected class of
      workers.

PMID- 11515152
TI  - [Assessment of exposure to laser radiation in research laboratories].
AB  - The problem of laser safety is now topical due to the wide use of laser systems
      in different working environments. The program of prevention and protection
      prescribed by law 626/94 gives general rules for the elimination (where possible)
      and/or reduction of risk factors. For this purpose, it is important to determine
      the parameters that characterize such risks. The Maximum Permissible Exposure
      (MPE) and the Nominal Ocular Hazard Distance (NOHD) are the most important
      parameters of laser safety. The evaluation of these parameters requires a
      detailed knowledge of the standards and of the various techniques which are
      necessary to measure them. In particular, the MPE parameters are obtained by CEI
      EN 60825-1 standard in relation to wavelength and emission duration of the
      investigated laser. Exposure to laser radiation is usually measured in terms of
      irradiance (W/m2) or radiant exposure (J/m2). The experimental values of
      irradiance must be compared with the MPE parameters obtained by safety standards.
      When the values of irradiance exceed the MPE parameters then the NOHD values must
      to be calculated. The aim of this paper is to offer a general view of the methods
      for measuring the above-mentioned parameters for the laser sources that are most
      widely used in research environments and to compare such parameters with those
      recommended by safety standards. Our results indicate that for almost all the
      laser sources analysed, the measured exposure values were greater than the MPE
      recommended by standards, both for eyes and skin. High values of NOHD indicate
      that it is necessary to use eye protection, beam stops or attenuators at the end
      of the useful beam path in normal working conditions and especially in research
      laboratories in which these conditions can often change.

PMID- 11515154
TI  - [Characterization of thoracic fraction of airborne particular matter (PM10) in a
      urban area and in adjacent building].
AB  - The aim of this study was to describe from a physico-chemical point of view the
      particles constituting the thoracic fraction of the airborne particulate matter
      (PM10) collected in two sampling stations: one in an urban area and another in an
      adjacent office building. The different sources contributing to the PM10 were
      identified and the relationship between the indoor PM10 and the outdoor PM10
      assessed. Also the seasonal trend of PM10's physico-chemical characteristics was
      evaluated. Four particulate samplings were conducted between April 1999 and
      February 2000. The samples were analyzed by scanning electron microscopy with EDS
      X-ray attachment. The data sets, consisting of the atomic concentrations of the
      constituent chemical elements of the particulate, were subjected to Hierarchical
      Cluster Analysis to determine the principal components of PM10. The statistical
      analysis method allowed us to identify seven groups (clusters) of similar
      particles in the particulate matter: C-rich particles, carbonates, silica,
      silicates, sulphates, Fe-rich particles, metals. The seasonal trend of PM10
      showed an increase in the alumino-silicates particles and a minor increment in
      sulphate particles in the summer. Moreover carbonaceous particles with a surface
      coating containing S were observed in the fine fraction of both outdoor and
      indoor particulate. This sulphurous coating turned out to be a strongly season
      dependent feature. On the whole, the results suggest that the characteristics of
      indoor PM10 largely depend on the characteristics of outdoor PM10; the outdoor
      particulate quality had a major influence on the indoor particulate particularly
      during the summer season.

PMID- 11515155
TI  - [What type of health surveillance should be applied to people previously exposed
      to asbestos?].

PMID- 11515156
TI  - [Suitable. For the time being].

PMID- 11515162
TI  - Ear identification based on surveillance camera images.

PMID- 11515163
TI  - Forensic archaeology, forensic anthropology and human rights in Europe.

PMID- 11515164
TI  - The Paddington rail crash: identification of the deceased following mass
      disaster.

PMID- 11515165
TI  - Quantitation of amphetamine-type compounds for which no reference compound is
      available: the validation of a theoretical model.

PMID- 11515166
TI  - Development of a harmonised pan-European method for the profiling of
      amphetamines.

PMID- 11515167
TI  - Drug administration and sexual assault: sex in a glass.

PMID- 11515168
TI  - New synthetic drugs in the European Union.

PMID- 11515169
TI  - Capillary electrophoresis: a new tool in forensic medicine and science.

PMID- 11515175
TI  - [Osteoporosis: end of therapeutic nihilism].

PMID- 11515176
TI  - [Epidemiology and costs of osteoporosis].

PMID- 11515177
TI  - [Cellular senescence: a mechanism of the development of osteoporosis?].
AB  - Osteoporosis is one of the most common diseases of the elderly. This leads to the
      hypothesis that the ageing of the organism is reflected as a cytogerontological
      effect in a specific loss of bone cell function. Three underlying pathogenetic
      mechanisms need to be considered: (1) cellular aging in general, (2) impairment
      of the systemic stimulation of bone formation by e.g. decreasing hormone levels,
      and (3) lower cellular effectiveness of cytokines and growth factors. Cellular
      aging consists of replicative and postmitotic senescence. While the replicative
      senescence limits only the number of cell cycles, the postmitotic aging is
      influenced by endo- and exogenous factors. These lead to genetic alterations
      known as delayed persistent genomic instability and to an increasing impairment
      of specific cellular functions. In the postmitotic phase, osteopenia caused by
      the decrease of systemically available sexual hormones is a major field of
      research. Osteopenia caused by a decreased activity of locally effective
      cytokines and growth factors is becoming increasingly understood. New therapeutic
      strategies, which modulate the local osteoblast activity, e.g. in bone defect
      healing, are under development. In conclusion, cellular senescence is considered
      to be one element in the development of bone loss. Potential therapeutic targets
      may open up an additional path in the treatment of local and systemic
      osteopenias.

PMID- 11515178
TI  - [Genetics of osteoporosis].
AB  - Osteoporosis is a disease affecting mainly women but also an increasing number of
      men. The destruction of the bone microarchitecture and the reduction of bone mass
      lead to increased fragility and pathologic bone fractures. Family studies and
      twin studies have shown that peak bone mass, mechanical strength, and
      physiological bone turnover are subject to genetic control. Vitamin D receptor
      polymorphisms were one of the first genetic factors suggested to influence bone
      phenotype, although their impact on bone metabolism was initially overestimated.
      Meanwhile, polymorphisms in numerous other genes such as collagen I alpha 1,
      estrogen receptor, transforming growth factor beta (TGF-beta), interleukin-1,
      interleukin-6, calcitonin, parathyroid hormone, and apolipoprotein E have been
      found to be associated with bone mineral density. In the interpretation of
      genetic findings, genetic differences between different ethnic groups,
      environmental factors such as calcium intake, vitamin D status, hormonal status,
      body size, and total body bone mineral density have to be considered.
      Understanding the molecular physiology of the genes described in this article and
      all genes influencing bone metabolism identified in the future will enable us to
      identify persons at risk for osteoporosis and to develop more specific therapies.

PMID- 11515179
TI  - [Leptin: factor in the central nervous system regulation of bone mass.
      Development of a new understanding of bone remodeling, skeletal reconstruction,
      skeletal preservation and skeletal repair].
AB  - Bone remodeling is the physiologic process used by vertebrates to maintain a
      constant bone mass between the end of puberty and gonadal failure. Besides the
      well-characterized and critical local regulation of bone remodeling, recent
      genetic studies have shown that there is a central control of bone formation, one
      aspect of bone remodeling. This central regulation involves leptin, an adipocyte
      secreted hormone that controls body weight, reproduction, and bone remodeling
      following binding to its receptor located on the hypothalamic nuclei. This
      genetic result in rodents is in line with clinical observations in humans and
      offers a whole new direction for research in bone physiology.

PMID- 11515180
TI  - [Laboratory diagnosis of osteoporosis].
AB  - Bone is biologically a highly active tissue whose cells are embedded in a complex
      network of systemically acting hormones and local mediators. The mechanisms of
      action involved are as yet only partially understood. With the increase in life
      expectancy and the resultant change of the population's age structure, diseases
      of the musculoskeletal system and bones have increased in importance. Thus,
      research is directed to a greater extent toward bone metabolism and the most
      frequent bone disease, osteoporosis. Until a few decades ago, the diagnosis of a
      bone disease was based principally on clinical and radiological methods.
      Laboratory methods only included the measurement of total alkaline phosphatase
      activity and calcium and phosphate balance. The development and introduction of
      new biochemical markers of bone metabolism in recent years led to a considerable
      increase in available laboratory methods. To evaluate the activity of
      osteoblastic synthesis, alkaline phosphatase and other bone-forming markers with
      higher tissue specificity such as bone alkaline phosphatase, osteocalcin, and
      several collagen propeptides are used. Bone degradation (calcium and
      hydroxyproline were the only markers until several years ago) can now be detected
      quickly and reliably with many new serological and urinary markers. Pyridinium
      derivatives and telopeptides as products of the metabolic activity of osteoclasts
      have been proved efficacious in diagnosis and therapy control.

PMID- 11515181
TI  - [Bone densitometry and ultrasound studies of the bone: methods, indications and
      efficacy].
AB  - The amount of calcium-containing crystals in bone tissue can be determined by
      osteodensitometry. The most common methods use X-ray energy. Two-dimensional
      approaches (dual-energy X-ray absorptiometry, DXA) have to be distinguished from
      volumetric measurements (quantitative computed tomography, QCT). Using
      ultrasound, broadband ultrasound attenuation (BUA) and ultrasound transmission
      velocity (SOS) can be measured. The results measured are correlated to fracture
      risk. Thus, considering the criteria of evidence-based medicine, these
      measurements are suitable for estimating the individual risk for osteoporotic
      fractures. Measurements can be recommended to persons with evidence for an
      increased osteoporosis risk based on the patient's clinical data and family
      history. According to a recommendation of a WHO working group in 1994, definition
      of osteoporosis can be based on osteodensitometry, which has now been widely
      accepted. Nowadays, we are able to evaluate the usefulness of osteodensitometry
      using X-ray energy for patient follow-up and treatment monitoring. However, not
      enough data are available with regard to ultrasound measurements. The correct use
      of these methods implies the observance of and attention to quality standards as
      defined by a working group of the Osteology Association ("Dachverband Osteologie"
      in the German-speaking countries).

PMID- 11515182
TI  - [Glucocorticoid-induced osteoporosis].
AB  - Osteoporosis due to steroid therapy is one of the most frequent and serious
      adverse events of antirheumatic therapy. The greatest loss of bone occurs during
      the 1st year of steroid intake, with the largest loss in the spine. Up to 50% of
      the patients, mostly postmenopausal women, suffer vertebral fractures. The
      prevalence of osteoporosis in 60-year-old patients with rheumatoid arthritis (RA)
      is more than double compared to the normal population. There are more risk
      factors other than age, gender, and menopause. Independent from the underlying
      disease, glucocorticoid therapy is associated with a high risk of osteoporosis
      development. Among the clinical manifestations of osteoporosis, fractures of the
      vertebrae, hips, and ribs are the most common. In clinical practice, bone density
      measurements are mostly performed with the dual-energy X-ray absorptiometry (DXA)
      technique. Since prevalent vertebral fractures are strongly predictive of new
      fractures, X-rays of the lumbar and thoracic spine are indicated in patients who
      are scheduled to receive steroid therapy for > 3 months. The value of serologic
      bone markers has not yet been clearly established. On the basis of these risks
      and the high prevalence of already manifest osteoporosis, there is a clear
      indication for osteoprotective therapy in RA. Bisphosphonates and active vitamin
      D metabolites play an important role for therapy and prophylaxis of steroid
      induced osteoporosis. In rheumatology it is often necessary to administer
      bisphosphonates intravenously due to the disability of the patients. The clear
      necessity for prophylaxis and therapy of steroid-induced osteoporosis must be
      stressed. Efforts should be intensified to ensure even more consistent
      application in daily practice. Doctors should treat their steroid patients on the
      basis of the clear-cut indications for intervention despite budget problems.

PMID- 11515183
TI  - [Secondary osteoporosis induced by anticoagulants?].
AB  - Generalized osteoporosis is a result of different causes and pathogenic
      mechanisms, which often combine forces to become clinically relevant. Among the
      different exogenic factors, drugs play an important role, frequently in
      connection with other factors such as immobilization or pregnancy. It has been
      suggested that anticoagulation therapy with heparins or coumarins may induce
      osteoporotic changes or enhance the development of osteoporosis for other
      reasons. According to in vitro experiments, preclinical trials, and clinical
      investigations, it seems reasonable to assume that heparins induce increased bone
      loss in a time- and dose-related manner. Low-molecular-weight heparins most
      likely have less effect on bone turnover when compared to unfractionated heparin.
      Oral anticoagulation therapy with vitamin K-antagonists is believed to have a
      weak effect on induction of osteoporosis, but clinical studies are contradictory.
      In spite of the fact that a relevant effect of these drugs on the induction of
      osteoporosis is questionable, it must be taken into consideration that
      anticoagulant drugs may enhance the negative effects on bone density of other
      risk factors capable of inducing osteoporosis such as immobilization, pregnancy,
      or endocrinological disorders.

PMID- 11515184
TI  - [Fluorides and bisphosphonates in the treatment of osteoporosis].
AB  - The therapeutic aim in osteoporosis to maintain or increase bone mass can be
      achieved by inhibition of osteoclastic resorption (antiresorptive treatment),
      stimulation of osteoblastic formation (anabolic treatment), or a combination of
      both strategies. Antiresorptive therapy of osteoporosis with the nitrogen
      containing bisphosphonates alendronate and risedronate is regarded today as
      evidence-based medicine. A significant reduction in the number of patients with
      new vertebral fractures has been documented already after 1 year. Anabolic
      therapy with fluoride was studied less extensively. The low price of fluoride
      salts and the lack of a patent protection may have contributed to this deficit in
      large studies. However, several recent medium-sized trials with a low-dose
      fluoride regimen consistently show a continuous increase in bone density and also
      a decrease in the rate of new fracture events. In our own pilot study with
      intermittent etidronate/fluoride therapy, we found significantly additive effects
      on bone mineral density. A larger trial with this therapeutic strategy using
      fractures as the primary endpoint would be of great interest.

PMID- 11515186
TI  - [Surgical possibilities in the treatment of diseases and injuries of the spine in
      patients with manifest osteoporosis ].
AB  - In the presence of a vertebral injury or disease, manifest osteoporosis affects
      preoperative planning. Thus, if surgery is indicated, bone density should be
      determined in cases of suspected or diagnosed osteoporosis. Instrumentation of
      the spine is frequently not required in surgical interventions. However, if
      indicated, instrumentation should be fixed multifocally and the deformity should
      be corrected with special care. It is absolutely necessary to avoid ending
      instrumentation within a kyphosis.

PMID- 11515185
TI  - [Hormone replacement and selective estrogen receptor modulators (SERMS) in the
      prevention and treatment of postmenopausal osteoporosis].
AB  - For many years, hormone replacement therapy (HRT) has been regarded as one of the
      most reliable means of prophylaxis and treatment for postmenopausal osteoporosis.
      As HRT ameliorates menopausal symptoms, it is widely prescribed among early
      postmenopausal women. A variety of different modes of replacement that suit each
      individual requirement are available in terms of schedule (cyclic or combined
      application of gestagens) and route of application (oral or transdermal). HRT
      effectively prevents spinal bone loss and delays bone loss at the hip up to a
      very old age. With continued use after menopause, HRT might theoretically halve
      the incidence of vertebral and hip fractures. However, long-term use or use of
      HRT in old age is rarely practiced, and the actual benefit of a transient use for
      future fracture prevention remains unclear. Raloxifene is the first member of the
      novel class of selective estrogen receptor modulators (SERMs) that has been
      approved for the prophylaxis and treatment of postmenopausal osteoporosis. It
      combines the positive effects of estrogen on the skeleton with estrogen
      antagonistic effects on sex tissues. Thus, raloxifene maintains bone mass and
      decreases the incidence of vertebral fractures in osteoporotic women, but avoids
      many of the side effects that are responsible for the poor long-term compliance
      to HRT such as resumption or continuation of regular menses, breast tenderness,
      or breast cancer. It even markedly reduces the risk of breast cancer. Both
      estrogen and raloxifene are characterized by a large number of extraskeletal
      effects that have to be taken into account when counseling postmenopausal women
      on the use of these agents for the prevention or treatment of osteoporosis.

PMID- 11515187
TI  - [Skin burns caused by electrosurgical devices. Legal liability aspects].

PMID- 11515188
TI  - [Meta-analysis of the Italian studies on short-term effects of air pollution].
AB  - BACKGROUND: In recent years, much attention has been given to review reports on
      the early effects of air pollution on health, measured through daily series of
      deaths and/or hospital admissions. A number of large planned meta-analyses (in
      which methods for data retrieval and processing are commonly planned a priori for
      all participating centers) are on going both in the US and in Europe. The
      National Mortality, Morbidity and Air Pollution Study included data from 90 US
      cities, whereas APHEA (Air Pollution and Health, a European Approach) considers
      data from about 30 european cities. The present paper summarizes methods and
      findings of MISA, a meta-analysis of data from 8 Italian cities. It belongs to an
      ad hoc supplement of Epidemiologia & Prevenzione (Epidemiol Prev 2001; 25 (2)
      Suppl: 1-72), the official Journal of the Italian Association of Epidemiology,
      which contains a full description of the study. MISA was launched on March 2000,
      within the project "Statistics, Environment and Health" (GRASPA), funded by the
      Italian Ministry of Education. Additional support was given by the Authorities of
      the 8 participating cities (from North to South: Turin, Milan, Verona, Ravenna,
      Bologna, Florence, Rome and Palermo). DAILY HEALTH DATA: Deaths certificate and
      hospital admission data have been collected respectively from the Local Health
      Authority and regional files. The same programme for retrieval of data on
      selected hospital admissions for acute conditions was used in the 8 cities. Main
      data are summarized in Table 1. DAILY CONCENTRATION OF POLLUTANTS: Most data were
      obtained from Regional Environmental Protection Agencies, which are responsible
      for environmental monitoring since 1993. Verona, Palermo and Milan (1990-94) data
      were obtained from local sources. Monitors with more than 25% of missing data
      were excluded. Meteorological data were collected by the same monitors and
      completed with data from monitors situated in the suburbs or (in Milan and
      Bologna) in the airport. The monitors were selected by a group of experts to
      ensure comparability. For SO2 and NO2 daily averages of hourly measurements were
      used, whereas concentrations of ozone and CO were estimated as the maximum 8
      hours moving average. Total suspended particulate or PM10 were measured as 24
      hours deposition. All analyses used the whole range of observed values (Table 2).
      Daily data were considered as missing when more than 25% of hourly data were not
      available. Missing data in one monitor were imputed as average of data from the
      remaining monitors weighted by the ratio between the specific monitor's year
      average and the general year average of all the selected city monitors. Missing
      data in one day were imputed as average of four days (preceding and following
      day, the same day of the previous and following weeks). In the city of Florence
      and Palermo PM10 concentrations were available. For the other cities we applied a
      conversion factor from PTS to PM10 (0.6 for Turin and 0.8 for all the others)
      estimated through validation studies. Ozone concentrations were used only where
      background monitors were available (Turin, Verona, Bologna and Florence) and
      limited to the warm season (May through September). METHODS: A common protocol
      for the city-specific analyses was defined on the basis of a structured
      exploratory analysis. The adopted basic model was a Generalized Additive Model
      for Poisson data. Effect estimates were age-adjusted (0-64, 65-74, 75+) and
      formal tests of interaction pollutant-age were conducted. In the first two age
      groups, indicator variables for seasonality were specified, and cubic splines
      with fixed number of degree of freedom were specified for the last age group and
      for all age groups for the morbidity data. Model adequacy was checked by residual
      analysis and inspection of the partial autocorrelation function. In a sensitivity
      analysis non linear pollutant effects were considered and overdispersed [table:
      see text] transitional models were fitted; the analysis was conducted for all
      lags 0-3 and some distributed lags (0-1, 1-2, 0-3); no multipollutant models were
      fitted. The same model was fitted to the city data. No model selection was done:
      Table 3 describes the steps in model building. In the meta-analysis, for each
      outcome, the estimates for each pollutant and for each city were combined using
      fixed and random effects models. Heterogeneity of effects was tested according to
      DerSimonian and Laird. Results were checked using a hierarchical bayesian model,
      which was used to investigate heterogeneity across cities in a meta-regression
      phase. Non informative priors were used. Posterior distributions of parameters of
      interest have been obtained with WinBUGS. 10,000 iterations (excluding [table:
      see text] the first 2000) were retained, while for the meta-regression 100,000
      iterations (excluding the first 4000) were stored. To approximate the marginal
      posteriors only one sample out of five were used. Achieved convergence was
      assessed using the Gelman and Rubin approach. In the meta-regression the models
      specified were the following: [formula: see text] i denotes city, j calendar
      period (1990-1994; 1995-1999). The first model includes only period as effect
      modifier, while the second model other potential variables. The ui terms (which
      do not vary with j) represent city specific random effects. RESULTS: For each
      pollutant, the meta-analysis detected a statistically significant association
      with mortality for natural causes. But for ozone, positive associations were
      commonly found for death and hospital admissions for both cardiovascular and
      respiratory diseases. Indeed, the only estimates whose lower 95% confidence limit
      bore a negative sign regarded the association between PM10 and mortality from
      respiratory diseases. Ozone in the warm season was positively and significantly
      associated with daily mortality and mortality for cardiovascular diseases whereas
      other estimates did not reach statistical significance and some were negative
      (only lag 0-1 for external comparability are reported in Table 4). Risks were
      highest (up to 4%) for respiratory conditions (Table 4). They were more
      pronounced at lag 1-2 for mortality, and at lag 0-3 for hospital admissions. Age
      was an effect modifier for mortality, the elderly being more susceptible. In the
      random effect meta-analysis, at lag 1-2, excess risks for unit increase of the
      pollutants at age 75+ and at age 0-64 were respectively: 4.9% and -0.4% for SO2,
      1.7% and 0.6% for NO2; 2.3% and 0.2% for CO. Corresponding figures for PM10 at
      lag 0-1 were 1.1% and 0.2%. The effect of PM10 on mortality [table: see text] was
      greater during the warm season (2.8% vs 0.8%). A complete analysis is reported in
      the Italian text. Here we provide some details on the effects of PM10, about
      which the residual heterogeneity across cities was highest (Table 4). In
      addition, the epidemiological evidence on the hazards from this fraction of
      particulate matter is more controversial. Table 5 reports the excess risk
      estimated through the meta-analysis in 1995-99 for a 10 micrograms/m3 increase of
      PM10 for some outcomes. Proper prior distributions (overdispersed normal and
      inverse gamma) were adopted in the final bayesian analyses. The sensitivity of
      results to the choice of the priors were investigated (we defined proper and
      improper uniform, student's t), obtaining comparable results. Total natural
      mortality was significantly heterogeneous across cities (Q = 18.96, 5 df, p <
      0.001). City-specific estimates are represented graphically in Fig. 1. As
      expected, the confidence (credibility) intervals are widest [table: see text] for
      bayesian estimates, intermediate for those obtained under a random effects model,
      and narrowest for those found under a fixed effects model. Nevertheless,
      differences in point estimates are negligible. A North-South gradient in risk is
      obvious. Table 6 shows, for the cities for which mortality data were available,
      the improvement in precision and the shrinkage of effect estimates toward the
      overall mean introduced by the bayesian modelling. In the meta-regression, total
      mortality and a deprivation score were associated with greater effects. The
      excess risks on hospital admission were modified by the deprivation score and by
      the NO2/PM10 ratio. Overall, the risk estimates were greater in the calendar
      period 1995-99 and there was a North-South gradient, with larger effects in
      cities located in Central and Southern Italy (Florence, Rome, Palermo).
      CONCLUSIONS: The meta-analysis of the Italian studies on short-term effects of
      air pollution in 8 cities, MISA, exhibits the following features: With the
      exception of Naples, all greatest Italian cities were included; overall a
      population of 7 million was enrolled. The study protocol was accurate with regard
      to the selection of hospital admissions for acute conditions. Monitored data of
      concentration of pollutant were carefully evaluated before their inclusion in the
      meta-analysis. City specific analyses were carried out according to a common
      protocol controlling for seasonality, influenza epidemics, age and meterological
      variables; [table: see text] the protocol derived from a structured exploratory
      analysis. The meta-analysis was done using fixed and random effects models; a
      hierarchical bayesian model was fitted in a sensitivity analysis. The
      heterogeneity of effects across cities was investigated using a hierarchical
      bayesian model for meta-regression. While mortality data are of good quality,
      hospital admission data are more problematic. Since the filing criteria for the
      latter changed around 1995, comparability of results before and after such date
      is limited. Moreover, hospital admissions rely on availability of beds, the offer
      of which may be restricted during the warm season. Comparability of pollutant
      concentration estimates among cities may have been influenced by differences in
      monitor characteristics. (ABSTRACT TRUNCATED)

PMID- 11515189
TI  - [Patient education before orthopedic elective interventions. "The Lagenthal model
      of 3-step patient education"].
AB  - There is still quite a controverseY when and how an informed consent should be
      obtained from a patient in the surgical field. As has been stated of the federal
      court the patient need to be given that information which is understandable to
      him and which will not cause him undue anxiety. This information has to be
      sufficient for the decision whether to proceeD or decline a surgical procedure.
      The federal courts are therefore asking for the optimal patient consent not
      necessarily the total and complete revelation during the patient information. For
      this reason the act of obtaining an informed consent was thought to be turned
      into a scientific question in identifying the base from optimal quality of giving
      informed consent respecting at the same time the principal of evidence based
      medicine. The support presents a sample of an oral and written consent-form given
      in three stages as it is currently being used in the orthopaedic service of the
      Langenthal hospital. 100 patients were given this type of a consent and were
      later on asked for their opinion of acceptance. Most of the patients felt to be
      sufficiently informed on their procedure after having undergone a three times
      repeated interview as well as having been given a consent form including hand
      drawings concerning their particular procedure. The advantages as well as the
      disadvantage of this type of consent form are being discussed.

PMID- 11515191
TI  - [Bone screw osteosynthesis of medial femoral neck fracture in elderly patients].
AB  - This study evaluated the complication rate and surgical outcome following
      cannulated screw fixation of femoral neck fractures in elderly patients. Between
      1.6.97 and 31.12.98 we operated on 110 patients with 112 fractures. The mean age
      was 78.4 years (range 25-96 years). Mean follow up was 6.8 months (range 3-16
      months). The mortality rate was 22.7% (25/110). 60 patients with 61 fractures
      could be evaluated for complications, reoperations, pain and walking ability.
      68.9% of the fractures healed. Avascular necrosis developed in 18%. Non-union
      rate was 8.2% and redislocation rate 4.9%. 18 patients needed a second operation,
      two thirds received an arthroplasty and one third had implant removal or
      replacement. In 81.6% of the patients (the patients with secondary arthroplasty
      excluded) pain relief was good. Insufficient reduction and malposition of the
      screws are the most common causes for failure of cannulated screw fixation of
      femoral neck fractures in the elderly.

PMID- 11515190
TI  - [Cecum volvulus--a frequently misdiagnosed disease picture. Results of a
      retrospective study of 26 patients and review of the literature].
AB  - BACKGROUND: Cecal volvulus represents a rare disease which causes acute or
      chronic intermittent mechanical obstruction. Diagnosis of the acute form of cecal
      volvulus is often established too late with resulting high morbidity and
      mortality. This study characterizes the typical clinical symptoms, radiological
      signs and the frequent concomitant diseases, based on a rather large number of
      patients. We specifically evaluated possible differences concerning clinical
      presentation, therapy and postoperative course of patients with vital bowel as
      opposed to necrotic cecum. PATIENTS AND METHODS: 26 consecutive patients
      hospitalised with cecal volvulus from January 1984 until February 2000 were
      retrospectively evaluated. Patients with vital intestine (n = 14) were compared
      to those with necrotic cecum (n = 12). RESULTS: 38% of patients underwent
      previous abdominal surgery, 34% suffered from other acute disease, in 38% cecal
      volvulus was associated with a neuropsychiatric disorder. 58% of the patients
      showed symptoms of intestinal obstruction. The clinical pattern of patients with
      necrotic cecum was not significantly different from those of patients with vital
      intestine. Diagnosis of cecal volvulus could be established in 77% by plain
      abdominal X-ray alone or by an additional contrast enema. CONCLUSIONS: Knowledge
      of the characteristic pattern of history, physical findings, plain abdominal X
      ray and the frequently with cecal volvulus associated diseases most often allows
      to establish diagnosis of cecal volvulus without delay and other diagnostic
      procedures. Astonishingly we found no major difference between vital and necrotic
      cecum with regard to clinical presentation and postoperative course.

PMID- 11515192
TI  - [Water jet dissection in fatty tissue].
AB  - BACKGROUND: The first report about the use of water-jet dissection in surgery
      dates 1982. The advantage compared to conventional cutting is the preservation of
      vessels and nerves, thus facilitating the precise coagulation thereafter. Devices
      of the new generation with coherent jet are used in liver surgery in order to
      reduce blood loss. The use of water-jet dissectors in other fields of surgery is
      currently under investigation. The preparation of vessels in fatty tissue is of
      special interest for plastic surgeons. The technical parameters of the hydro- or
      water-jet device have to be optimised. METHOD: Abdominal fat tissue of fresh
      cadavers was cut under standardised conditions with different parameters of the
      dissector. The depth of the cuts and the morphology of the blood vessels were
      analysed. RESULTS: Between 20 and 60 Bar cutting pressure of the water-jet and
      one single pass the cuts are 8 mm deep. Deeper cuts can be achieved by repeated
      application on the same cut. When using 40 Bar and 5 passes the cutting depth is
      1.7 cm. Higher pressure as 50 or 60 Bar do not lead to deeper cuts. The water-jet
      dissection leads to a water uptake of the cut tissue. Morphologically all the
      vessels, lying in the cut are undamaged if the pressure doesn't exceed 40 Bar
      pressure range. CONCLUSION: The optimal pressure for water-jet dissection of
      fatty tissue lies between 30 and 40 Bar. Higher pressure does not lead to deeper
      cuts, but increases the risk of vessel damage. The vessels in the remain
      morphologically intact if he cutting pressure lies below 50 Bar. The effect of
      the mechanical irritation of the vessels has to be investigated in vivo, before
      using the water-jet dissector for preparation of blood vessels in humans e.g. for
      flap dissection.

PMID- 11515193
TI  - [Scooter injuries or a chronicle of a new epidemic. Apropos of a prospective
      study of Geneva cases].
AB  - AIM: Confronted with an increasing number of an unpowered scooter-related injury
      and an absence of available data in the literature, we undertook a prospective
      and exploratory study, in order to assess the circumstances and trauma
      consequences of this kind of injury. METHOD: Between the 15th of August 2000 and
      the 15th of November 2000, each child consulting our emergency room for a scooter
      related injury was questioned about the circumstances of the accident and his
      general scooter experience. Data about all injuries and there treatment were
      collected. RESULTS: 32 children (16 B/16 G) with a the mean age of 10.1 +/- 2.3
      years have consulted. Eight children (25%) required hospitalization. In almost
      half of the cases, the injury was caused by direct or indirect material facts. No
      child was wearing protection at the time of the accident. Fracture was the most
      frequent injury (55%) and the upper limb was concerned by almost half of the
      lesions. Four fractures required osteosynthesis (12.5%) and six treatments a
      general anesthesia (19%). The severity of injury and the treatment were more
      substantial when the unpowered scooters were used for transport rather than for
      playing. CONCLUSION: Our short study gives a first estimation of the potential
      danger of the unpowered scooter and its confrontation with the traffic, without
      prevention given by the law or the producer. However this product can lead to
      important injuries.

PMID- 11515194
TI  - [Rupture of the Achilles tendon after local steroid injection. Case reports and
      consequences for treatment].
AB  - It is known that Steroids increase the risk for tendon ruptures. Despite this
      local steroids are still used in the treatment of achilles tendinitis. Three
      cases are demonstrated. All of them show an unusual rupture mechanism.
      Intraoperatively necrotic tendon changes are seen. All patients receive an open
      tendon reconstruction with healthy, autologous material. Although there is a
      delayed healing in one case, all patients show favourable results one year
      postoperatively with return to full range activity levels and are able to
      participate in sports.

PMID- 11515195
TI  - Late rupture of an abdominal aortic aneurysm after Parodi's endoprosthesis
      replacement.
AB  - Endovascular surgery as a whole, and specifically in the context of aortic
      aneurysms, is a very interesting methodology the potential of which is
      increasingly being recognized. Follow up information on patients who underwent
      these procedures will be critical to validate the different techniques which have
      been developed and to identify the most appropriate situations for this type of
      surgical procedures. The authors present a case of aortic aneurysm rupture who
      had undergone Parodi's endoprosthesis placement two years before. CT angiographic
      evaluation showed a wide endoleak due to distal stent detachment, a complete
      dislodging of the endoprosthesis itself and retroperitoneal haematoma. Prosthesis
      replacement through a laparotomic approach was carried out and the patient was
      discharged 10 days postoperatively, surgically cured.

PMID- 11515196
TI  - [The human factor].

PMID- 11515197
TI  - [Progressive and idiopathic hearing loss].

PMID- 11515198
TI  - [Diseases from Chlamydia trachomatis].

PMID- 11515199
TI  - [Diseases from Chlamydia psittaci and Chlamydia pneumoniae].

PMID- 11515200
TI  - [Iatrogenic torsades de pointes].

PMID- 11515202
TI  - [Black-out from angel trumpets? How long after the consumption of angel trumpets
      can the consciousness-altering effect last?].

PMID- 11515201
TI  - [Anticonvulsant weaning? How should anticonvulsant therapy be discontinued?].

PMID- 11515204
TI  - [Role of the pediatric hospital in the prevention and management of child abuse].

PMID- 11515205
TI  - [Role of pediatric psychiatry in a child protection team (CAN team du CHUV)].

PMID- 11515206
TI  - [Role of secondary prevention in a specialized consultation for sexual abuse and
      negligence].

PMID- 11515207
TI  - [Outcome of small girls, victims of incest].

PMID- 11515208
TI  - ["Violence and psychotherapy": what transfers? Some experiences in private
      practice].

PMID- 11515209
TI  - [Psychopathologic profiles of children consulting for problems of violence
      compared to a control group].

PMID- 11515210
TI  - [When family violence leads to social violence, is there only one way to
      overcome? How to liberate oneself?].

PMID- 11515211
TI  - [The psychic envelope and violence. Reflections on our psychologic practice in
      the therapeutic day center].

PMID- 11515212
TI  - [Violence in a child psychiatric institution: challenge to consider?].

PMID- 11515213
TI  - [Destiny of violence: from traumatization to its symbolic expression].

PMID- 11515214
TI  - [Adolescents from the south, sick from an unequal exchange].

PMID- 11515215
TI  - [Humanism and the history of medicine. The construction of medical practice
      values].

PMID- 11515216
TI  - ["Research in general practice"].

PMID- 11515217
TI  - [Pyogenic infections in general practice].
AB  - Between 1944 and 1996 in comparable Middle-European general practices the
      statistical figures of superficial pyogenic infections had dropped remarkably.
      That had not be known up to now. Tonsillitis, otitis media and appendicitis did
      not show that decrease. In the literature the author did not find relevant
      papers.

PMID- 11515218
TI  - [Case statistics and life expectancy].
AB  - The trial to find connections between the frequency of cases in general medicine
      and life expectancy of the population succeeded, concerning superficial pyogenic
      infections by meta-analysing cases-statistics 1944-1996. More could be found by
      special, prospective, well-planned, comparable statistics of long duration,
      although it is unlikely that such expensive and difficult investigations will
      ever be made.

PMID- 11515219
TI  - [Epidemiologic research in general medicine].
AB  - To succeed in creating comparable cases-statistics in general practice (= family
      medicine) requires a specific scientific basis. So far, only R. N. Braun was able
      to meet those requirements, whilst world-wide other epidemiologists failed to
      develop suitable frequency-statistics of results of consultations on the medical
      front-line.

PMID- 11515220
TI  - [Specialists in applied medicine and diagnosis].
AB  - Clinical specialists are not yet exploring the vast field of medicine applied by
      them. As a consequence, clinical medicine is in need of suitable names for many
      results of consultations. The concept "diagnosis" has become insignificant in
      specialists' medicine. Only specific basic research can alter this disturbed
      balance between clinical science and practice.

PMID- 11515221
TI  - [Problems in early diagnosis of malignancies in general medicine].
AB  - If specialists expect general practitioners to carry out extensive investigations
      serving early detection of diseases they don't consider how limited in that
      respect the possibilities of general practitioners are. In general, practice
      however the early detection of malignancies is satisfactory if the doctor makes
      use of the short time available the best possible.

PMID- 11515222
TI  - [Principle aspects of early detection of dangerous diseases].
AB  - One aim of applied medicine is to uncover, as early as possible, avoidably
      dangerous courses of diseases. All attempts to install obligatory investigations
      for the early detection of certain malignancies in general practice have failed
      for various reasons. The success rate for detecting life-threatening diseases in
      general practice could be rather high, if all the new tools, developed by basic
      specific research, were applied.

PMID- 11515223
TI  - [Uncharacteristic fever from a special professional theory viewpoint].
AB  - Non-characteristic fever is an excellent example to demonstrate how basic
      research in general practice has raised the level of dealing with one of the most
      frequently met problems in primary care. Especially diagnostic protocols and the
      casugraphy are very helpful tools of the family physician (general practitioner-)
      instead of coping with the problem of limited time and means and lack of an
      appropriate education by experience and intuition only.

PMID- 11515224
TI  - [Current concepts in therapy of reflux disease].
AB  - Proton pump inhibitors have replaced H2-blockers as first line agents for the
      therapy of gastroesophageal reflux disease due to their effective acid
      suppression and faster healing rate. The endoscopic severity of esophagitis and
      the clinical response are the most important determinants of dosing and duration
      of therapy. In patients with severe esophagitis continuous maintenance treatment
      with proton pump inhibitors is recommended. In recent years antireflux surgery
      has been established as an important alternative therapy.

PMID- 11515225
TI  - [Diagnosis and differential diagnosis of consciousness disorders from the
      psychiatric viewpoint].
AB  - Diagnosis and differential diagnosis of disturbance of consciousness are often
      difficult, especially when occurring in the course of psychiatric diseases. Apart
      from discord in defining the term of consciousness it is not always easy to
      distinguish between qualitative and quantitative alterations of the disorders.
      The performance of an exact interview and a thorough clinical examination allows
      an estimation of the degree of dimming of consciousness as well as the possible
      causes. Disorder of Consciousness is often found in patients carrying out
      substance abuse but also in the course of other psychiatric diseases such as
      depression, schizophrenia, personality disorders and dissociative disorders. This
      article is dealing with the clinical approach towards patients experiencing
      alterations or disturbances of consciousness and is also trying to communicate
      innovations in the field of psychiatric diagnostics.

PMID- 11515226
TI  - Development and sensory evaluation of soy milk based yoghurt.
AB  - Yoghurts were prepared by fermentation of soy milk using a mixed starter culture
      containing Lactobacillus bulgaricus and Streptococcus thermophilus. Soy milk at 9
      degrees Brix was homogenised under pressure (17 MPa) and fermented with and
      without addition of sucrose (2.0 and 2.5 g per 100 g) for 4, 5, 6 and 7 hours.
      The yoghurts were evaluated in terms of sensory quality, pH, titrable acidity,
      phytic acid and oligosaccharides: A yoghurt with the best sensory quality was
      obtained using the homogenised soy milk with 2% sucrose addition and fermented
      for 6 h. Lactobacillus bulgaricus and Streptococcus thermophilus did not produce
      phytases and alpha-galactosidases at the experimental conditions, consequently,
      phytic acid and galactosides were not affected by the process.

PMID- 11515227
TI  - [Chromium content in foods and dietary intake estimation in the Northwest of
      Mexico].
AB  - Chromium is an indispensable nutrient for the carbohydrates and lipids
      metabolism. In this study the chromium content in the twenty main foods of the
      diet from Northwestern Mexico was determined, as well as the daily mean intake
      which was estimated based on the food intake basket of this region. Chromium
      content was analyzed by atomic absorption spectrophotometry using the graphite
      furnace technique and previous digestion of foods in microwave oven. The chromium
      mean intake was estimated considering the chromium daily mean intake for person
      per day and the chromium content of the foods analyzed in this study. The range
      chromium content in the foods analyzed was between 0.0004 and 0.1641 microgram/g
      dry weight. White cheese showed the highest chromium content followed by pasta
      soup, wheat tortilla, bread and meat. The main foods chromium contributors in the
      diet were: wheat tortilla (20%), white cheese (11%), corn tortilla (11%), pasta
      soup (10%), milk (10%), meat (9%) and white bread (8%). The daily chromium intake
      was 30.43 +/- 1.6 micrograms/d. Chromium values obtained in the food analyzed are
      considered low. Moreover, chromium intake obtained from the diet is not enough to
      meet the safety and adequate daily chromium intake. Therefore, the population
      from the Northwestern Mexico has a suboptimal dietary chromium intake.

PMID- 11515228
TI  - [Prevalence of nutritional anemia in women of reproductive age. Costa Rica.
      National nutrition survey, 1996].
AB  - In 1996, The Ministry of Health and Inciensa conducted the latest National
      Nutrition Survey, to provide support and guidance to the national policies, plans
      and programs in the field of food and nutrition. The present paper reports the
      results for the prevalence of anemia estimated in a total of 884 women of
      reproductive age, in three areas: metropolitan area, other urban areas and rural
      areas. Anemia was determined through measurements of hemoglobin, plasma ferritin
      and plasma folates. In addition, hemoglobin patterns were determined by
      electrophoresis. The cutt-off points used were those recommended by the WHO.
      Anemia was present in 18.6% of the women. Severe to moderate deficiency of iron
      (< 12 ng/dl) and of folates (< 6 ng/dl) were found in 43.2 and 24.7% of women
      respectively, with statistically significant differences by area of residence.
      The magnitude of the problem for anemia can be classified as mild, for iron
      deficiency as severe, and for folate deficiency as moderate. In conclusion,
      Anemia represents a public health problem for Costa Rica that has remained
      constant throughout the last decade. In women of reproductive age, iron
      deficiency is the main cause of Anemia, followed by folates deficiency, and in a
      small percentage hemoglobinopathies. Intestinal parasites are not longer a mayor
      cause of Anemia. Prevalence of Anemia is influenced by place of residence, but
      not by age. In summary, despite the favorable health conditions present in Costa
      Rica, the prevalence of Anemia and of iron deficiency are similar to those of the
      Latin-American region. To improve this situation, public health interventions are
      necessary.

PMID- 11515229
TI  - [Prevalence of sub-clinical vitamin A deficiency and malnutrition in slum
      children in Maraicabo - Venezuela].
AB  - The present cross sectional study was carried out to estimate the prevalence of
      vitamin A deficiency among children by means of clinics and conjunctival
      impression cytology (CIC), and nutritional status by anthropometric indicators
      H//A, W//A, W//H. The study population included 157 children 2-6 y old, from
      urban and rural slums of Maracaibo, Venezuela, Conjunctival impression cytology
      was performed by ICEPO standard procedure. Z-score was applied to anthropometric
      data with reference values of NCHS-WHO. No evidence of clinical or ophthalmologic
      signs of vitamin A deficiency were detected. The prevalence of subclinical
      vitamin A deficiency, as detected by abnormal CIC, was 35.4%, being higher in
      rural children (48.3%). These prevalence values are higher than the criteria laid
      down by WHO/UNICEF to indicate a public health problem (> 20%). Mild or moderate
      protein-energy global malnutrition and stunting were detected in 36.1% and 44.6%
      of children, respectively. Abnormal CIC was indistinctly observed (approximately
      equal to 35%) as much in children with adequate nutrition as in malnourished
      ones. There was no significant difference in the distribution of the CIC results
      in relation to nutritional status. The findings indicate that CIC and Z-score of
      nutritional anthropometric data are useful to characterize the risk of vitamin A
      deficiency and of malnutrition in communities. Beside the implementation of an
      integral nutritional program which includes supplementation, food fortification
      and dietary diversification, improvement of socio-economic and sanitation
      conditions and also the educational level, with emphasis on nutritional and
      health education, are highly recommended.

PMID- 11515230
TI  - [Zinc levels in term and preterm milk].
AB  - Zinc is an essential element, important for early growth and development, and
      immune competence, which deficiency might be especially critical in preterm
      infants. Since published data have shown that some preterm milks have abnormally
      low zinc values, we decided to measure zinc levels in term and preterm milk, in
      order to assess if they were within normal values and if there were differences
      between both groups. Samples from 24 preterm and 20 term mothers (mean
      gestational age, 30.9 + 0.5 and 39.5 + 0.2 weeks, respectively) were collected
      and kept at -20 degrees C until analyzed by atomic absorption spectrophotometry,
      prior wet ashing with nitric acid. Both term and preterm milk showed zinc values
      within normal levels. No significant differences were registered between them. A
      decreasing trend was observed along time, which was significant between colostrum
      and mature milk samples (ANOVA, p < 0.05). In the term group, zinc concentrations
      in colostrum and mature milk (microgram/mL) (mean +/- SEM) varied between 6.96 +/
      0.69 y 2.44 +/- 0.11, while in the preterm group the values were 6.20 +/- 0.89 y
      2.28 +/- 0.54. According to our results, zinc values in human milk were
      comparable between preterm and term mothers.

PMID- 11515231
TI  - [Prevalence of anemia, iron and folate deficiency in children 7 years smaller.
      Costa Rica, 1996].
AB  - In 1996, were studied in Costa Rica 961 children with ages between one and six
      years, with representation for metropolitan, urban and rural zones of the
      country. The classification approaches applied were emitted by the Pan-American
      Health Organization and the World Health Organization. The preschooler population
      presented in the national environment a prevalence of anemia of 26.3% (children
      from 1 to 4 years with hemoglobin < 11.0 g/dL and those from 5 to 6 years old
      with hemoglobin < 12.0 g/dL). The prevalence of Iron depletion (Ferritin < 12
      ng/mL) and iron deficiency (Ferritin < 24 ng/mL) were 24.4% and 53.8%,
      respectively. The folate deficiency (< 6.0 ng/mL) was 11.4%. The iron deficiency
      was higher in children smaller than 4 years, being the maximum deficiency in the
      1 year-old (75%). More than 40% of the preschool children presented sub-clinical
      deficiency of iron; of them, 10% showed severe deficiency of iron without
      presence of anemia. The children from the rural area presented the highest
      prevalence of anemia and iron depletion, while the metropolitan area met more
      frequency with iron deficiency. The nutritional anemias still constitute a
      moderate problem of public health in Costa Rica. The main cause is iron
      deficiency, associated in small proportion with folate deficiency and other
      factors associated with the erythropoiesis.

PMID- 11515232
TI  - Association between prematurity and maternal anemia in Venezuelan pregnant women
      during third trimester at labor.
AB  - To determine the association and its magnitude between prematurity and anemia in
      women in their third trimester of pregnancy and at labor. An incident case
      control study was conducted using 2 controls per case. Data was obtained in a
      tertiary hospital in Valencia, Venezuela. A total of 543 women who delivered
      between May and December 1996 entered into the study. Women having a preterm
      delivery, less than 37 weeks of gestation at delivery, were defined as cases (n =
      181). Anemia was defined according to WHO as Hb less than 11 g/dL. Logistic
      regression was used to analyze the data and likelihood ratio test was done for
      model comparison. Maternal anemia was found to be significantly associated with
      prematurity (Odds Ratio: 1.70; 95% CI = 1.18 to 2.57 P = .001), after adjusting
      for Placental Abruption, PROM, Previous Premature Labor, Prenatal Care Visits,
      and Uterine Bleeding during more than one trimester. Maternal anemia at the end
      of the third trimester of pregnancy, at labor, was associated with an increased
      risk of prematurity.

PMID- 11515233
TI  - [Influence of breakfast on cognitive functions of children from an urban area in
      Valencia, Venezuela].
AB  - It's well known that physical growth and intellectual activity is influenced by
      nutritional status. With the purpose of evaluate the fasting effects on the
      cognitive functions, anthropometric state and cognitive functions (logic and
      school work performance), under fasting and post-breakfast condition were
      assessed in a group of 68 school children age 9 and 10 years, who studied in a
      private school (1998-1999). Logic reasoning was measured with Raven test and
      attention, precision, velocity and fatigue with the Lepez test. The main of the
      children (80%) were well-nourished and 20% had showed overweight. At breakfast
      condition all subjects were over 50 percentil for Raven test. Consumption of
      breakfast influence on logic reasoning (p < 0.001) and school work performance (p
      < 0.01). It is concluded that in these well nourished children, breakfast
      consumption improved cognitive performance.

PMID- 11515234
TI  - [The impact of malnutrition on brain development, intelligence and school work
      performance].
AB  - The findings from several authors confirm that undernutrition at an early age
      affects brain growth and intellectual quotient. Most part of students with the
      lowest scholastic achievement scores present suboptimal head circumference
      (anthropometric indicator of past nutrition and brain development) and brain
      size. On the other hand, intellectual quotient measured through intelligence
      tests (Weschler-R, or the Raven Progressives Matrices Test) has been described
      positively and significantly correlated with brain size measured by magnetic
      resonance imaging (MRI); in this respect, intellectual ability has been
      recognized as one of the best predictors of scholastic achievement. Considering
      that education is the change lever for the improvement of the quality of life and
      that the absolute numbers of undernourished children have been increasing in the
      world, is of major relevance to analyse the long-term effects of undernutrition
      at an early age. The investigations related to the interrelationships between
      nutritional status, brain development, intelligence and scholastic achievement
      are of greatest importance, since nutritional problems affect the lowest
      socioeconomic stratum with negative consequences manifested in school-age, in
      higher levels of school dropout, learning problems and a low percentage of
      students enrolling into higher education. This limits the development of people
      by which a clear economic benefit to increase adult productivity for government
      policies might be successful preventing childhood malnutrition.

PMID- 11515235
TI  - [Food based approaches to improve vitamin and mineral nutrition adequacy].
AB  - This paper, using the nutrient density concept and the development of Food-Based
      Dietary Guidelines (FBDG), explores the nutritional adequacy of food patterns
      based on the main staples around the world--maize, wheat, rice and potato. The
      nutritional adequacy of the vitamins A, C, folates and the minerals iron, zinc
      and calcium in diets composed by these staples is analyzed. Projected diets
      modified by the addition of foods high in vitamins and minerals, based on food
      table composition information, are analyzed for changes in nutritional adequacy,
      in order to cover the nutritional requirements of all family members. This
      theoretical exercise shows that diets diversified by the addition of relatively
      small quantities (27-70 g) of foods like fruits, vegetables, legumes and meat
      improve substantially the nutritional adequacy of the vitamins A, C, folates,
      iron and zinc. In the case of calcium, the addition of a dairy source becomes
      essential. From the practical point of view, the implementation of the food based
      approach requires a national effort in order to support the production of
      nutrient rich foods and to promote consciousness of nutrient bioavailability, so
      that people may obtain all nutrient potential from foods. Simultaneously, the
      need of fortification programs at the national level is recognized. This is the
      case for critical nutrients, where requirements might be above the potential in
      available foods. A similar situation occurs in the case of vulnerable groups like
      pregnant women and infants, who need supplementation to ensure nutritional
      adequacy of their diets. In conclusion, the use of FBDG is a good alternative for
      improving the nutritional adequacy of diets based predominantly on staple foods.
      However, food fortification and supplementation programs directed to vulnerable
      groups are necessary and complementary practices to the FBDG implementation.

PMID- 11515236
TI  - [Use of diet containing yeast protein (Saccharomyces cerevisiae): effects upon
      pregnancy, lactation and development in rats].
AB  - The nutritive value of manioc flour (Manihot esculenta) enriched with yeast
      protein (Saccharomyces cerevisiae) added to a food mixture most frequently
      consumed by low-income populations was assessed in female Wistar rats (n = 30;
      100-120 days old). Animals were divided into three groups, mated and had free
      access to diets and water. Diets were as follows: beans, rice, yeast-enriched
      manioc flour (BRYMF17); beans, rice, manioc flour (BRMF13); casein (17% protein)
      (CAS17). Body weight gains and food consumption were recorded during pregnancy
      and lactation. At the parturition, the number of pups per litter was recorded and
      offspring were uniformly distributed (7 pups per litter). Weight gains were
      determined until weaning (21 days). At weaning two youngs were selected from each
      litter and individually housed. Weight gains, food consumption and the length of
      the tail were measured until rats were 70 days old. Rats had their liver and
      brain removed for protein determination and wet and relative weights. Liver
      samples were histologically examined. Blood hemoglobin, hematocrit and proteins,
      as well as the Food Efficiency Ratio (FER), were determined. ANOVA and Tukey's
      test were used. The experimental diet had not significant effect on pregnant and
      lactating dams. Values for the investigated parameters were higher in
      experimental youngs than in their controls and lower than in the standard group.
      This yeast protein-enriched manioc flour proved to be valid in terms of dietary
      supplementation.

PMID- 11515237
TI  - Fruits and vegetables consumption among Costa Rican adolescents.
AB  - Scientific evidence indicates that lower levels of fruit and vegetables
      consumption are associated with an increased risk of developing cancer and
      cardiovascular disease. Therefore, an increase of these foods' consumption may
      substantially improve public health. The purpose of this study was to examine the
      consumption of fruits and vegetables in 214 urban and rural adolescents in
      relation to the 5-A-DAY recommendation. Mean daily servings of fruits (1.7
      servings) were not far from the minimum recommendation of 2 daily fruit servings.
      This mean decreased to 1.21 servings when banana was not counted. Mean vegetable
      intake (1.1 servings, including legumes) was well below the minimum
      recommendation of 3 vegetable servings per day. Urban adolescents and females
      consumed significantly (p = 0.000) fewer fruits and vegetables servings than did
      rural youngsters and males. However when pulses were not counted the mean daily
      servings of vegetables were higher in urban adolescents (p = 0.029). Only 16 from
      214 adolescents (6%) consumed five or more servings of fruits and vegetables per
      day. This proportion decreased dramatically to 2% (p = 0.000) when pulses and
      banana were not counted. Examination of the factors associated with low intake of
      fruit and vegetables could be beneficial to develop effective interventions
      targeted to increase their consumption among adolescents.

PMID- 11515238
TI  - [Nixtamalization cooking characteristics of 11 maize varieties].
AB  - In the present study, 11 maize varieties were analyzed for their nixtamalization
      cooking quality. The 11 varieties were grown in the same locality and in the same
      year. The samples were evaluated for their physical characteristics, such as
      moisture content averaging 13.3%, average 1000 kernel weight (312.5 g), grain
      hardness through density (1.28 g/ml) and percent floaters (9.5%). These data
      indicated that all maize varieties had a hard endosperm which is recommended for
      the nixtamalization cooking process. The 11 varieties were formed on the average
      by 5.7% seed coat, 11.5% germ and 82.8% endosperm. The low seed coat content
      suggest a low solids loss during processing. Cooking quality evaluation was done
      by applying a standard lime cooking procedure to all varieties. An average solid
      loss of 3.2% was measured, with 0.8% of seed coat still attached to the
      endosperm. Water absorption at the end of cooking was 40.8% without soaking and
      46.9% at the end of soaking. Nixtamal moisture was 47.9% after soaking and only
      41.5% at the end of cooking. Cooking time with soaking for 50% moisture in the
      grain varied from 69 to 122 minutes at 1500 meters over sea level. The cooked
      grain was dried with hot air and ground however, the particle size obtained was
      not as that in commercial nixtamalized maize flour. However, the cooking quality
      parameters to make dough and tortillas were acceptable, with a penetration index
      of hydrated flour of 178.6 mm, pH 7.97, water absorption index (WAI) of 3.23 g
      gel/g flour and 4.11% water solubility index (WSI). All flours from the 11
      varieties of maize gave acceptable tortillas as evaluated by physical
      characteristics and sensory quality. However of the 11 varieties 7 including the
      control were superior for nixtamalization cooking quality.

PMID- 11515239
TI  - Discrimination of Brazilian arabica green coffee samples by chlorogenic acid
      composition.
AB  - Coffee is basically consumed for the pleasure given by its taste and aroma, that
      is, the quality and acceptance of the coffee beverage are directly related to its
      sensorial characteristics. Thus, nowadays coffee quality is basically evaluated
      by sensorial analysis. However, together with this kind of analysis, it should be
      important to have available more objective chemical methods to assess coffee
      quality. One possible approach could be based on the analysis of chlorogenic
      acids (CGA), since they are considered precursors of coffee flavour and pigments
      during roasting. In the present work, high performance liquid chromatography
      (HPLC) analysis of chlorogenic acids was applied to six different Brazilian
      arabica green coffee samples which were previously characterised by sensorial
      analysis. The results showed the potential to correlate the chemical data,
      evaluated by the Principal Components Analysis (PCA) statistical method, with
      sensorial analysis in order to discriminate the quality of the samples. It was
      observed that the 3,4-dicaffeoylquinic (3,4-diCQA) and 3,5-dicaffeoylquinic (3,5
      diCQA) isomers are very important for grouping the coffees into good and bad
      samples.

PMID- 11515240
TI  - Nomenclature for describing the genetic characteristics of wild-type measles
      viruses (update). Part I.

PMID- 11515241
TI  - A nonimpact article about nonimpact injury.
AB  - If reports of this caliber are required to insinuate that significant "brain
      damage" may ensue from rather mild nonimpact injury, there is some a priori
      reason to believe that this is not the case. The introduction of security belts,
      head rests, side-impact protection, and air bags has made driving safer; yet, the
      incidence of "brain injury" is allegedly rising. To definitely settle this issue,
      we will have to wait for other, preferably prospective, randomized, double-blind
      studies yielding a higher class of evidence. So, what do we learn from this
      study? First, in the United States, it is possible to select a sample of
      litigants that after a car accident or similar injury behaves and complains the
      way they did, even if there was no proof of morphological brain damage. Second,
      reports like this headed by a misleading title should better go unpublished until
      certain minimal standards of scientific scrutiny are met.

PMID- 11515242
TI  - Nonimpact brain injury: neuropsychological and behavioral correlates with
      consideration of physiological findings: reply to Lang.

PMID- 11515243
TI  - Neuropsychological assessment, depression, and past exposure to organic solvents.
AB  - This study assessed neuropsychological performance in persons with a history of
      exposure to organic solvents and nonexposed healthy controls. Structured clinical
      interviews were also done to determine current Axis I diagnosis of mood disorder
      to assess the contribution of mood disorder to neuropsychological performance.
      Solvent-exposed participants were found to have significantly reduced scores on 3
      of 5 neuropsychological clusters (learning and memory, visuospatial, psychomotor
      speed) compared to controls. No differences were found between the groups on
      measures of general intelligence. Within the exposed group, 50% met current Axis
      I criteria for mood disorder. Hierarchical multiple regression, controlling for
      age and education, revealed that mood disorder was significantly related to
      performance on only the visuospatial domain. There was no association between
      mood disorder and measures of learning and memory, attention, motor speed, and
      general intelligence. Higher ratings of past exposure were associated with poorer
      scores on learning and memory tests and slower times on speeded tests. These
      findings are consistent with other research documenting deficits in
      neuropsychological and psychiatric functioning in exposed workers.

PMID- 11515244
TI  - Neuropsychological dysfunction, mood disturbance, and emotional status of
      munitions workers.
AB  - The objective of this study was to compare the neuropsychological function,
      emotional status, visual function, and illness prevalence of 265 former munitions
      plant workers (M age = 56.7 years, M years of education = 12.07; 201 African
      American, 64 White) exposed to organic solvents for an average of 17.03 years
      with that of a group of 77 unexposed controls (M age = 51.3 years, M years of
      education = 13.07; 30 African American, 47 White). Neuropsychological tests were
      selected from the World Health Organization Neurobehavioral Core Test Battery,
      Wechsler Adult Intelligence Scale-III (WAIS-III), and Wechsler Memory Scale-III
      (WMS-III) and also included the Brief Symptom Inventory, Profile of Mood States,
      Beck Anxiety Inventory, and Beck Depression Inventory. Vision tests included the
      Lanthony d-15 color vision, the Vistech Contrast Sensitivity, and the Snellen.
      The exposed group showed greater deficits than the controls in verbal learning
      (WMS-III Logical Memory I Learning Slope and Word Lists I Recall), visuomotor
      tracking speed (Cancellation H, WAIS-III Digit Symbol-Coding) and psychomotor
      function (Dynamometer and Grooved Pegboard), and dysfunction in emotional status,
      illness prevalence, and visual function. African American workers reported higher
      levels of exposure than Whites. Exposure relations demonstrated increased
      neuropsychological dysfunction with increased exposure.

PMID- 11515245
TI  - Executive and cognitive functions in patients with extreme obsessive-compulsive
      disorder treated by capsulotomy.
AB  - All patients treated with thermocapsulotomy for obsessive-compulsive disorder
      (OCD) at Karolinska Hospital between 1978 and 1990 were examined at follow-up
      with a comprehensive neuropsychological test battery. For comparative reasons the
      same test battery was applied to current patients with OCD, approved for
      capsulotomy. Both groups performed within the normal to subnormal range on most
      tests. In a subgroup of operated patients who did not complete all categories on
      the Wisconsin Card Sorting Test (WCST), there was a significant positive
      correlation between time elapsed after capsulotomy and number of categories
      completed on the WCST. The results would indicate that neuropsychological
      performance, in general, remains intact after capsulotomy. In some patients
      executive function is affected, but restoration may take place over time.

PMID- 11515246
TI  - The symbol trail making test: test development and utility as a measure of
      cognitive impairment.
AB  - Although the Trail Making Test (TMT) has proven to be an exceptional clinical
      tool, its applications have been limited by the instrument's use of the Arabic
      numeral system and Latin alphabet. Clearly an instrument not limited by a
      specific alphabet or numerical system could fill this void. This study presents
      the development and validation of an alternative to the TMT that offers modestly
      similar psychometric properties and can be used with populations that have no
      familiarity with the Arabic numerical system or a specific alphabet. The Symbol
      Trail Making Test (STMT), which employs symbols that are not language or
      numerically based was administered to a normative sample of 210 participants,
      including 54 individuals whose first language was not English, for the purpose of
      collecting normative data. Reliability, assessed through an alternate form
      administration, and convergent validity, assessed through correlation with the
      TMT in a nonpatient sample, was deemed acceptable. Significant discriminant
      validity was obtained comparing non-brain-injured patients to brain-injured
      patients, particularly on time measures. An analysis of variance found no
      significant difference between native English speakers and individuals speaking
      English as a second language on performance on the STMT. This preliminary study
      provides evidence that the STMT is a clinically useful instrument for
      discriminating brain-injured from non-brain-injured participants without
      employing a specific culture-bound symbol system.

PMID- 11515247
TI  - The "GRAS" status of women's work.

PMID- 11515248
TI  - Economic impact of on-site physical therapy.

PMID- 11515249
TI  - Paying doctors more: use of musculoskeletal specialists and increased physician
      pay to decrease workers' compensation costs.
AB  - Previous studies evaluating workers' compensation care systems used retrospective
      controls. We performed a concurrent effectiveness study comparing a WC system
      that used visiting musculoskeletal specialists to assist primary care physicians
      with a typical discounted-fee, WC, managed-care system. In the new specialist
      direct system, physicians could not profit from self-referral, but were paid 35%
      to 69% more per patient visit than doctors in the discounted-fee clinics. All
      claims filed by all employees of two hotels for 2 years were examined. Patients
      had self-selected either a specialist-direct or a discounted-fee clinic, and the
      entire cost of the claim was assigned to either system of care. Claim costs were
      63% lower in the specialist-direct system (P < 0.001). Medical costs were 45%
      less (P < 0.014), and indemnity 85% less (P < 0.001), in this system. Claims were
      closed nearly 6 months faster in the specialist-direct system (P < 0.0001).
      Indemnity claims were more common in the discounted-fee system (P < 0.0001).
      Claimant and injury characteristics were not significantly different between the
      systems. This new care model is a cost-effective alternative to discounted WC
      managed care. Discounting the services of the primary treating physician may
      result only in cost-shifting, not cost-saving.

PMID- 11515250
TI  - State-specific trends in smoke-free workplace policy coverage: the current
      population survey tobacco use supplement, 1993 to 1999.
AB  - We examined trends in smoke-free workplace policies among all indoor workers in
      the United States using the National Cancer Institute's Tobacco Use Supplement to
      the Census Bureau's Current Population Survey (total n = 270,063). Smoke-free was
      defined as smoking not permitted in public or common areas or in work areas of a
      worksite. Nationally, we found that nearly 70% of the US workforce worked under a
      smoke-free policy in 1999. At the state level, a greater than 30-percentage-point
      differential existed in the proportion of workers with such policies. Although
      significant progress has been made to reduce worker exposure to environmental
      tobacco smoke on the job, we predict further progress may be difficult unless
      comprehensive regulations to protect all workers are implemented at the national,
      state, or local level.

PMID- 11515251
TI  - Mortality from occupational exposure to environmental tobacco smoke in Finland.
AB  - This article aimed to estimate the mortality from exposure to passive smoking at
      work in Finland. The estimation used statistics on causes of death, exposure
      prevalences, and risk ratios from epidemiologic studies. The attributable
      fractions of cause-specific mortality from passive smoking at work were 2.8% for
      lung cancer, 1.1% for chronic obstructive pulmonary disease, 4.5% for asthma,
      3.4% for ischemic heart disease, and 9.4% for cerebrovascular stroke. Altogether,
      about 250 fatalities were estimated to have occurred in 1996. This is
      approximately 0.9% of the total mortality in the Finnish population in the
      relevant disease and age categories. The magnitude of mortality related to past
      occupational exposure to passive smoking is considerable. Preventive measures to
      reduce environmental tobacco smoke in the workplace will be a powerful means of
      reducing the high burden of respiratory and cardiovascular diseases.

PMID- 11515252
TI  - Identification of 1-adenine DNA adducts in workers occupationally exposed to
      styrene.
AB  - Styrene is an extensively used industrial chemical that has been classified as a
      possible human carcinogen. The possible carcinogenicity may be related to the
      covalent DNA binding properties of styrene 7,8-oxide, a major metabolite of
      styrene. We have developed a sensitive and a highly specific phosphorus-32
      postlabeling method for the determination of 1-styrene 7,8-oxide-adenine DNA
      adducts. These adducts were analyzed in white blood cells from workers exposed to
      styrene at mean level of 76.2 mg/m3. Three of nine exposed workers showed adducts
      above the detection limit; the mean was 0.79 +/- 0.14 1-styrene 7,8-oxide-adenine
      DNA adducts/10(9) nucleotides. None of the 11 control cells showed adducts above
      the detection limit, which was 0.4 adducts/10(9) nucleotides. The results show a
      potential of 1-adenine DNA adducts for predicting risks in the workers exposed to
      styrene.

PMID- 11515253
TI  - Association between smoking, acetaldehyde dehydrogenase-2 1-1 status, and alcohol
      drinking among Taiwanese polyvinyl chloride workers.
AB  - To study the factors affecting alcohol consumption among Taiwanese workers, we
      conducted an investigation of the association between alcohol drinking and
      smoking, aldehyde dehydrogenase-2 (ALDH2) status, alcohol dehydrogenase-2 (ADH2)
      status, any history of abnormal liver function, and hepatitis B and C viral
      infection. The subjects included 207 male workers who had been followed-up with
      respect to liver function periodically since 1992. Information relating to
      current alcohol consumption and smoking habits was obtained by an interviewer
      administered questionnaire in 1996, and any history of liver function and
      hepatitis B and C virus infection was obtained from previous medical
      surveillance. Genotypes of ALDH2 and ADH2 were determined by polymerase chain
      reaction/restriction fragment polymorphism assay. Results have revealed that
      smoking and ALDH2 1-1 status were associated with current alcohol consumption
      (respectively: odds ratio, 23.3; P < 0.01 and odds ratio, 14.5; P < 0.05).
      Neither a history of abnormal liver function nor a history of hepatitis B and/or
      C infection was associated with current alcohol consumption. It seems that only
      those with ALDH2 1-1 who are smokers consume alcohol. We conclude that smoking
      and inherited ALDH2 1-1 are the most important determinants of alcohol
      consumption. In addition to the medical advice of physicians in their yearly
      health check-ups, worksite health-promotion programs based on both alcohol
      consumption habits and smoking cessation should be instituted forthwith,
      particularly for those who demonstrate the potential for developing liver damage.

PMID- 11515254
TI  - Relationship of disability prevention to patient health status and satisfaction
      with primary care provider.
AB  - A sample of 625 patients aged 18 to 65 with primary care visits was used to
      explore the relationship of disability prevention to patient health status and
      satisfaction with health care provider. Disability prevention and the patient
      provider relationship, the latter a potential mediating factor, were measured
      using reliable and valid scales. The joint effects of disability prevention and a
      strong patient-provider relationship were associated with decreased risks for
      poor physical health, as measured by the Medical Outcomes Study 12-item short
      form health survey, decreased restricted activity days, and overall satisfaction
      with their primary care provider. Patient-provider relationship was independently
      associated with increased patient satisfaction with the provider overall and
      endorsement of the provider to family or friends. The evidence questions the
      conventional wisdom among some primary care providers that incorporating
      disability prevention principles into their daily practice jeopardizes patient
      satisfaction. These results suggest that primary care providers with strong
      patient-provider relationships can successfully add disability prevention to
      their practice.

PMID- 11515255
TI  - Evaluation of blink reflex results obtained from workers previously diagnosed
      with solvent-induced toxic encephalopathy.
AB  - We reviewed blink reflexes recorded from 51 railroad workers with long-term
      occupational exposure to solvents who were diagnosed by others with solvent
      induced toxic encephalopathy. No worker fulfilled conventional clinical criteria
      for dementia or trigeminal mononeuropathy. All workers had normal R1 and R2 blink
      reflex latencies. R1 latencies correlated significantly with several nerve
      conduction measures, including F wave latencies, suggesting that some
      intersubject variability reflected intrinsic conduction properties, not isolated
      brain-stem function. Although normal, the workers' R1 latencies were
      significantly prolonged compared with historical control groups, including gender
      matched control subjects of similar mean age (11.2 ms vs 9.9 ms; P < 0.0001).
      Stepwise multiple regression models demonstrated significant associations of R1
      latency with age and use of CNS-active prescription medications (P = 0.003), but
      duration of occupational solvent exposure did not enter into the models.
      Paradoxically, workers using CNS-active medications had significantly shorter R1
      latencies compared with workers not using such medications (10.9 vs 11.7 ms; P =
      0.01). Job title, another potential surrogate measure of exposure, was not
      significantly related to reflex latencies. The geographical site of predominant
      solvent exposure did influence R1 latency, and workers from one site had longer
      exposure duration and longer R1 latencies than remaining workers. However, an
      interaction between age and exposure duration (r = 0.39; P = 0.003) confounded
      interpretation of this observation. Disability or work status, mental status
      findings, or classification of encephalopathy did not influence blink reflex
      latencies. The overall results do not support, but do not entirely exclude, a
      possible relationship between subclinical blink reflex abnormalities and
      occupational exposure to solvents. Nevertheless, it is clear from these results
      that the small group differences in R1 latency between exposed workers and
      control subjects are of no diagnostic importance and of uncertain physiologic
      importance, and they may reflect unrecognized confounders and technical factors.

PMID- 11515256
TI  - Age-related physical fitness and the predictive values of fitness tests for work
      ability in home care work.
AB  - Despite the widespread assessment of physical fitness in occupational medicine
      and health services, only a few validity studies have been made of the fitness
      tests used in relation to job demands. The purpose of this study was to assess
      the physical fitness of female home care workers (n = 132) in relation to age and
      to evaluate whether the fitness tests used predict work ability over a 5-year
      period of follow-up. Muscle endurance declined by 18% to 37%, and isometric
      muscle strength by 10% to 18%, from the youngest (21 to 35 years) to the oldest
      (45 to 59 years) age group. The proportion of those subjects who could be
      classified below the average age-related fitness categories according to the
      maximal oxygen consumption was highest (50%) for the 21-to-35 age group. The
      logistic regression model showed that obesity (odds ratio [OR] = 7.51) and poor
      results on the sit-up (OR, 8.9), balance (OR, 6.5), and weight-lifting (OR, 4.6)
      tests predicted the highest risk for reduced work ability, according to the work
      ability index used in the 5-year follow-up. Moreover, average results for the
      trunk side-bending test (OR, 4.6), poor results for the squatting test (OR, 3.8),
      poor knee extension strength (OR, 4.2), and the average maximal oxygen
      consumption (l.min-1) (OR, 3.1) indicated a high risk for reduction in work
      ability. The physical fitness tests were strongly associated with the physical
      demands of home care work and were relevant for the evaluation of work-related
      fitness among home care workers.

PMID- 11515257
TI  - [Testing domestic and imported medical engineering products by the interference
      stability requirements].
AB  - The paper presents some conclusions on about the interference stability of
      medical engineering products, which have been made on the tests for requirements
      for electromagnetic compatibility of different kinds of products--from the
      simplest to the most elaborate life-support systems. It gives a list of basic
      standards for interference stability, as well as criteria for the quality of
      operation of the products tested for the stability.

PMID- 11515258
TI  - [Experience in designing equipment for testing technical means by the
      interference stability requirements].
AB  - The paper provides data on new standard documents on the electromagnetic
      compatibility and on appropriate equipment to test interference stability.

PMID- 11515259
TI  - [Test of medical electrical equipment by safety parameters: a new view].
AB  - The paper deals with tests of medical electrical equipment in the light of GOST
      standards P 50267.0-92 and P 51350-99 with regard to the experience gained in
      applying these standards.

PMID- 11515260
TI  - [A device for measuring the output power of UHF therapy apparatuses with
      condenser and inductive applicators].
AB  - The paper considers a new device for measuring the output power of UHF therapy
      apparatuses with condenser and inductive applicators. The special feature of the
      device is that independent element calibration in the wanted frequency range may
      be used; other measuring instruments do not possess this property.

PMID- 11515261
TI  - [Use of absorbing tongs to measure the output of radio interferences].
AB  - Information on the absorbing tongs consisting of two sets of ferrite rings and a
      wide-band current collector, which are designed to measure the emissive power of
      radio interferences in the supply circuit and interblock conducting wires at
      frequencies greater than 30 MHz.

PMID- 11515262
TI  - [Metrological problems in testing medical ultrasound equipment].
AB  - The paper deals with the testing of medical ultrasound equipment. The parameters
      of transducers of this equipment with regard to their use and the type of
      acoustic exposure are presented. Information on work under way in Russia on the
      metrological support of ultrasound measurements is given.

PMID- 11515263
TI  - [Standardization and certification of medical devices].
AB  - The paper deals with the problems associated with the absence of a well-defined
      standard basis of the standardization, licensing, etc. of medical engineering
      articles, which the public corporation "Izhevsk Motor Plant Axion-Holding", one
      of the largest manufacturers of medical equipment comes up against.

PMID- 11515264
TI  - [Principles in the designing of an impedance electrosurgical apparatus for
      reliable resection of oncologic tumors and involved biological tissues].
AB  - The paper proposes that for more reliable resection of cancer tumors and involved
      biological tissues during a surgical intervention, the structure of biological
      tissues should be evaluated by measuring its impedance at two frequencies: 2 and
      440 KHz and by calculating the polarization coefficient (Cpolar). Examining
      Cpolar changes in intact and pathologically altered biological tissues allowed
      them to be distinguished during a surgical intervention by employing an impedance
      electrosurgical apparatus.

PMID- 11515265
TI  - [Use of three-valued logic to enhance the stability of interpretation algorithms
      in medical diagnostic devices].
AB  - The procedure proposed for converting the binary production principles to the
      three-valued form, the relationship found between the well-known three-valued
      logic networks, and the particular properties of three-valued logic expressions
      permit introduction of the mechanisms that are responsible for three-valued
      production principles and the construction of logic conclusions by the results of
      this variation. The apparatus designed ensures a higher stability of ECG
      interpretation without lowering its efficiency and makes it possible to estimate
      the quality of interpretation by the capacities of the apparatus itself.

PMID- 11515266
TI  - [Optic method of searching for acupuncture points and channels].
AB  - A procedure is proposed to search for acupuncture points and channels (APC) by
      space-sensitive recording of optical radiation diffusely reflected by surface
      (dermal and hypodermal) tissues of the body. For this purpose, the body surface
      is probed by low-intensity infrared radiation from a laser or noncoherent (light
      emitting diodes) source by using a fiber-optic multichannel sensor. It is shown
      that it is most advisable to apply sources at wavelengths of 840-850 and 1260
      1300 nm.

PMID- 11515267
TI  - [Standardization and certification of medical devices: results and prospects].
AB  - The paper presents the concept of standardization and certification of medical
      articles, which has been worked out by the State Committee of Russia for
      Standardization, and the results of the first stage of harmonization of the ISE
      and ISO standards with the national ones.

PMID- 11515268
TI  - [Analysis of the effectiveness of algorithms in enhancing the informative value
      of X-ray images in digital fluorography].
AB  - The paper deals with the synthesis of algorithms for non-linear control of the
      degree of contrast of digital chest images by bringing the baseline histogram of
      brightness to the prearranged form and with practical analysis of the efficiency
      of the algorithms derived.

PMID- 11515269
TI  - [Development of standardization and certification of the quality of medical
      devices].
AB  - Some issues of harmonization of the Russian standards for medical articles with
      the international standards, including the European Engineering Legislation are
      considered. Under the present conditions, the rules and procedures of
      certification of medical articles are associated with the consumer quality
      controlling system. A list of new Russian standards in the above area is given.

PMID- 11515270
TI  - [Psychophysiological traits of personality and the specific features of heart
      rhythm regulation under the influence of occupational activities].
AB  - The paper presents the results of experimental instrumental studies of the
      psychophysiological features of regulatory properties of the nervous system under
      the influence of emergency factors. The investigations were made in the students
      of a navigation college before and after at least 6-month navigation on board the
      transport ship. Whether there is an association of adaptive behavioral responses
      with cardiac rhythm regulation under the influence of occupational activities was
      studied.

PMID- 11515271
TI  - [Algorithmic support of the estimation of expenditures of medical services during
      dental treatment].

PMID- 11515272
TI  - [Informational computer simulation of limiting infectious process via sterilizing
      medical instruments and equipment by means of electrochemically activated aqueous
      solutions].

PMID- 11515273
TI  - [Use of international standards in designing artificial respiration apparatuses].
AB  - The paper considers the specific features of the use of the international
      standards introduced in Russia, which pertain to artificial ventilation
      apparatuses, in designing these apparatuses.

PMID- 11515274
TI  - [Reflections on pulmonary stenosis after an arterial switch operation].

PMID- 11515275
TI  - [Genetics of dilated cardiomyopathy].
AB  - Dilated cardiomyopathy is one of the leading causes of heart failure and a
      primary cause for heart transplantation in patients below the age of 40 years.
      Despite major advances in diagnostic procedures such as examination of myocardial
      biopsies, the etiology remains unknown in many patients. Chronic inflammation or
      myocarditis and chronic alcohol abuse are considered two main etiologic factors
      in dilated cardiomyopathy. A third causal factor, namely genetic transmission of
      the disease, is at least as common as myocardial inflammation or toxic damage.
      Several prospective studies of relatives of patients with dilated cardiomyopathy
      proved that about 25-30% of all cases are of familial etiology. The most common
      mode of inheritance is autosomal dominant. Less frequently is the disease
      inherited as an X-chromosomal trait. Autosomal recessive and mitochondrial
      transmission is rare. The penetrance is highly variable and age dependent. Many
      relatives of patients with DCM show only minor cardiac abnormalities and it is
      unknown whether they progress to full cardiomyopathy in later life. Examination
      of families has identified so far eight disease genes, namely the dystrophin,
      tafazzin, cardiac actin, desmin, lamin A/C, delta- sarcoglycan, cardiac beta
      myosin heavy chain, and cardiac troponin T gene. Certain mutations in lamin A/C
      cause conduction system disease and dilated cardiomyopathy, whereas other
      mutations cause in addition skeletal muscle myopathy. Dystrophin mutations are
      the cause of the rare X-linked dilated cardiomyopathy without skeletal muscle
      involvement and a progressive course in young men. Other mutations in the
      dystrophin gene, mainly deletions, are the cause of the muscular dystrophy Becker
      and Duchenne which also present with dilated cardiomyopathy. Mutations of the
      desmin,   delta-sarcoglycan, the cardiac actin and beta-myosin heavy chain as
      well as the troponin T gene are known to cause autosomal dominant-dilated
      cardiomyopathy without other abnormalities. The infantile X-linked DCM is caused
      by mutations of the tafazzin gene. The onset of the disease is typically within
      the first year of life and death occurs usually in childhood. Most patients may
      in addition be characterized by skeletal myopathy, short stature, neutropenia and
      abnormal mitochondria, also referred to as Barth syndrome. Knowledge of the DCM
      disease genes led to the new hypothesis that dilated cardiomyopathy is a disease
      of the myocardial force generation or force transmission. Many more disease loci
      are known but the responsible disease genes are not yet identified. Better
      understanding of the expression and function of disease genes may eventually
      result in new diagnostic and therapeutic tools in order to improve the prognosis
      of this severe disorder.

PMID- 11515276
TI  - [Peroxisome proliferator-activated receptors (PPARs) in the vessel wall: new
      regulators of gene expression in vascular cells].
AB  - Peroxisome proliferator-activated receptor alpha and gamma (PPAR alpha, PPAR
      gamma) are nuclear transcription factors regulating gene expression in response
      to their ligands. Initially, PPARs were identified as regulators of gene
      expression in lipid metabolism and adipogenesis, but recent work has demonstrated
      PPAR expression in vascular cells and suggests antiinflammatory properties in the
      vasculature. Since PPAR alpha activators include lipid-lowering fibric acid
      derivatives and since PPAR gamma can be activated by antidiabetic
      thiazolidinediones, activation of these receptors might be an intriguing tool to
      influence atherogenesis in patients with vascular disease. However, there is also
      evidence that PPAR activators might furnish lesion development under certain
      circumstances. The following review will focus on these aspects of potential anti
      or proatherogenic effects in the vessel wall and discuss potential clinical
      implications of these findings.

PMID- 11515277
TI  - [Onset, stability and electrogram width criteria: efficacy and safety in the
      detection of supraventricular tachycardia in implantable cardioverter
      defibrillators].
AB  - Inadequate therapies for supraventricular tachycardia (SVT) by implanted
      cardioverter defibrillators (ICD) are potentially arrhythmogenic and impair the
      patient's quality of life. Inadequate detection (ID) of SVT can be reduced by
      using detection enhancements like the onset- and stability criteria (O + S) or
      the electrogram width criterion (EGW). 103 patients (85 male, 18 female, mean age
      65 +/- 9 years, mean ejection fraction 40 +/- 16%) were initially randomized to O
      + S active (Onset 12/89%, Stability 30 ms) or O + S inactive in the lowest
      detection zone. Cross-over between O + S active and O + S inactive occurred every
      3 months. In 40 patients (39%) with ICD capable of EGW, this feature was
      programmed to passive. The number of ID was referred to 1 year of follow-up.
      During the follow-up period (485 +/- 226 d), 31 patients (32%) developed SVT in
      the lowest detection zone, 11 patients (11%) ventricular tachycardia (VT) and 14
      patients (14%) both. In total, 387 SVT and 127 VT were observed. The mean number
      of ID was 10.7 +/- 4.8 ID/year with inactive O + S, and was significantly reduced
      to 1.1 +/- 0.3 ID/year when O + S were active (p < 0.0001). During the whole
      study period no delayed or inhibited adequate therapy for VT due to O + S was
      observed. During follow-up using EGW (n = 40), when O + S were inactivated,
      resulted in a significant reduction from 19.8 +/- 11.6 to 0.5 +/- 0.2 ID/year (p
      = 0.007). Even while O + S were active EGW would further reduce ID from 1.2 +/-
      0.5 to 0.2 +/- 0.1 ID/year (p = 0.028). However, 2 adequate therapies of VT in 2
      patients would have been suppressed if EGW had been activated. This results in a
      sensitivity of 98% and a specificity of 93% when O + S were inactive and
      respectively 95 and 79% when O + S were active. The empirical programming of O +
      S is therefore a safe method for the reduction of ID in patients with ICD. Using
      EGW leads to further reduction of ID but may lead to underdetection in individual
      cases.

PMID- 11515278
TI  - Linear and non-linear dynamics of heart rate variability in brain dead organ
      donors.
AB  - Recent studies outlined linear and non-linear dynamics in heart rate variability;
      however, their physiological origin is still unknown. The present study
      investigated the impact of cerebral function on linear and non-linear dynamics in
      heart rate variability. Electrocardiograms from seven brain dead organ donors and
      seven healthy volunteers were analyzed. Atropine was used in healthy volunteers
      to adjust their heart rate to that of the donors. As compared to healthy
      volunteers without atropine, the linear dynamics of heart rate variability,
      determined by time and frequency domain analyses, were significantly reduced in
      healthy volunteers with atropine and, to an even greater extent, in donors.
      Atropine tended to increase the complexity and non-linearity of heart rate
      variability in healthy volunteers, as determined by the correlation dimension D
      and the largest Lyapunov exponent L, respectively (D = 9.43 +/- 2.93 vs. 7.65 +/-
      0.97 and L = 0.525 +/- 0.099 vs. 0.504 +/- 0.047 bits.beat-1; both NS), while
      these indices were significantly reduced in donors by 19.5 +/- 12.8% and 15.0 +/-
      11.7%, respectively (D = 6.16 +/- 0.98 and L = 0.428 +/- 0.059 bits.beat-1; both
      p < 0.05 vs. volunteers). Thus, loss of cerebral function reduces both linear and
      non-linear components of heart rate variability.

PMID- 11515279
TI  - [Bradycardia despite hyperthyroidism].
AB  - Hyperthyroidism is usually associated with tachycardia, hypothyroidism with
      bradycardia. After observing clinically inapparent hyperthyroidism in patients
      requiring pacemaker implantation, we studied the occurrence of hyperthyroidism in
      patients receiving a first permanent pacemaker. Of 237 patients (age 71.4 +/- 8.9
      years; 54.9% females), 16 (6.75%) had subclinical (TSH < 0.1 mE/l and fT3 < or =
      9.0 pmol/l) and 4 (1.69%) overt hyperthyroidism (TSH < 0.1 mE/l and fT3 > 9.0
      pmol/l). Prevalence of hyperthyroidism was similar to that in the general
      population. Compared to euthyroid patients, in the patients with subclinical or
      overt hyperthyroidism there were significantly more females (n = 16) than males
      (n = 4; p = 0.018). Hyperthyroid patients were older (75.0 +/- 9.6 vs. 70.7 +/-
      8.9 years; p = 0.015). At follow-up, all patients had a relevant proportion of
      pacemacer-induced beats. Clinical signs of hyperthyroidism or cardiac symptoms
      were not different between groups. In conclusion, bradycardia does not exclude
      the presence of hyperthyroidism. Temporary pacing is recommended in
      thyreotoxicosis with bradycardia. In contrast, primary implantation of a
      permanent pacemaker appears to be adequate in patients with bradycardia,
      cardiovascular disease and an additional diagnosis of hyperthyroidism.

PMID- 11515280
TI  - [Treatment of supravalvular pulmonary stenosis after arterial switch operations
      (ASO)].
AB  - The aim of this study was to evaluate the incidence of postoperative pulmonary
      supravalvular stenosis in patients with d-TGA and to assess the rate of success
      or failure of balloon angioplasty. Out of 70 patients with d-TGA 67 patients
      underwent successful arterial switch operation. Twelve children developed severe
      supravalvular pulmonary stenosis with a peak gradient above 50 mmHg (range: 50
      120 mmHg). In these patients 19 high pressure dilatations were performed up to a
      diameter of 130% of the native valve dimension. The mean age at angioplasty was
      17 months (range: 3-36 months). Successful intervention was defined as a > 50%
      decrease of predilatation peak pressure gradient or right ventricular pressure <
      50 mmHg. Dilatations were performed without complications. Complete resolution
      was primarily achieved in 1 patient. In 7 patients the pressure gradients could
      be reduced to 10-45 mmHg (mean: 25 mmHg). In another two patients a palliative
      stent-implantation into the pulmonary trunk was necessary to reduce the pressure
      gradient. Because unsuccessful intervention, two patients needed subsequent
      operation. During follow-up of 6-9 months after intervention severe restenosis
      occurred in 3 patients (2 after stent-implantation; 1 after re-re-dilatation) who
      then also needed operation. Balloon dilatation should be the first treatment in
      patients with pulmonary stenosis after ASO in TGA owing to the low complication
      rate and the potential benefit of this procedure. Recurrent and combined stenoses
      with narrow pulmonary valve annulus should be treated surgically.

PMID- 11515281
TI  - [Balloon dilatation of the pulmonary valve. Short-, middle- and long-term
      results].
AB  - BACKGROUND: Immediate and long-term results after balloon dilatation of pulmonary
      valve stenosis in our unit. METHODS AND PATIENTS: All 111 patients (1 day-18
      years) who have had balloon dilatation of a pulmonary valvar stenosis between
      12/1987 and 8/1997 were divided into 4 groups: Typical valvar pulmonary stenosis
      (group A; n = 78), stenosis with dysplastic pulmonary valve (group B; n = 10),
      critical pulmonary stenosis (group C; n = 16) and pulmonary atresia after
      transcatheter or operative opening of the valve (group D; n = 7). Patients with
      pulmonary stenosis and complex congenital heart disease were excluded. RESULTS:
      The average systolic transvalvular gradient was reduced from 68.5 to 27.2 mmHg
      (60%) immediately after balloon dilatation. After a follow up of 48.8 +/- 37
      months 101 patients could be reevaluated. In group A (n = 69 at FU) and C (n = 16
      at FU) 81% showed a systolic transvalvular gradient < 30 mmHg after one and 83%
      (A) respective 94% (C) after two balloon dilatations. In group B (n = 9 at FU)
      44% exhibited a systolic gradient < 30 mmHg after one and 56% after two balloon
      dilatations. In group D (n = 7 at FU) 57% showed a systolic gradient < 30 mmHg
      with no further improvement by a second dilatation. Over all, 80% of our patients
      could be treated sufficiently by transcatheter means. The rate of major
      complications was 7.3% with no lasting residuals at follow up and no deaths.
      CONCLUSION: Balloon dilatation of the pulmonary valve is secure and effective.
      Best results are obtained in patients with typical pulmonary valve stenosis and
      in newborns and infants with critical pulmonary valve stenosis.

PMID- 11515282
TI  - [Intravascular ultrasound guided directional atherectomy and stent implantation
      of an unprotected main stem in a heart transplant patient with comorbidity].
AB  - Following orthotopic heart transplantation (HTx), development of transplant
      vasculopathy (TVP) is the limiting medical entity leading to significant
      morbidity and mortality beyond the first year after HTx. Selection of a suitable
      strategy for repeat revascularisation--transcatheter angioplasty, coronary artery
      bypass grafting or repeat HTx--depends on various parameters including coronary
      morphology, left ventricular performance, comorbidity, availability of graft
      material and donor organs. Catheter-based interventions on the main stem of the
      left coronary artery are feasible, but a relatively lower primary success rate
      and a higher complication rate and significantly increased mortality have to be
      expected. We report on a patient who underwent HTx 9 years ago and developed
      severe transplant vasculopathy revealing significant main stem stenosis, making
      reintervention necessary. Due to age, coronary artery morphology and comorbidity
      the patient was not considered for coronary artery bypass grafting or repeat HTx.
      We performed successful IVUS-guided directional coronary atherectomy and stent
      implantation on a distal stenosis of the unprotected main stem. Our case
      demonstrates a predictable procedural risk and favourable primary result of left
      main stem angioplasty procedures, thus providing a therapeutic option for
      patients who are poor candidates for operative revascularisation strategies.

PMID- 11515283
TI  - [Late complications after transcatheter closure of atrial septal defect].
AB  - The transcatheter closure of atrial septal defects is generally accepted as an
      alternative to surgical therapy in selected patients. Potential complications of
      these devices are a matter of concern, as well as the very complicated
      implantation technique required for some systems. We report on a 17 year old
      patient in whom embolization of a fractured umbrella arm into a peripheral branch
      of the left pulmonary artery occurred. A 35 mm-ASDOS-Device (protected trademark
      of the Dr. Osypka GmbH/Grenzach-Wyhlen, Germany) had been implanted 4 years ago.
      The perfusion scintigraphy of the left lung showed normal pulmonary blood flow.
      Echocardiography failed to demonstrate instability of the double-umbrella device.
      The patient was always free of any symptoms. Due to the permanent stresses
      between device and heart, late fractures of the device and embolizations of
      fragments are possible. It can be concluded that patients who underwent
      transcatheter closure of an ASD require lifelong follow-up.

PMID- 11515284
TI  - Curriculum "practice of cardiac pacing".

PMID- 11515285
TI  - The dynamics of embodiment: a field theory of infant perseverative reaching.
AB  - The overall goal of this target article is to demonstrate a mechanism for an
      embodied cognition. The particular vehicle is a much-studied, but still widely
      debated phenomenon seen in 7-12 month-old-infants. In Piaget's classic "A-not-B
      error," infants who have successfully uncovered a toy at location "A" continue to
      reach to that location even after they watch the toy hidden in a nearby location
      "B." Here, we question the traditional explanations of the error as an indicator
      of infants' concepts of objects or other static mental structures. Instead, we
      demonstrate that the A-not-B error and its previously puzzling contextual
      variations can be understood by the coupled dynamics of the ordinary processes of
      goal-directed actions: looking, planning, reaching, and remembering. We offer a
      formal dynamic theory and model based on cognitive embodiment that both simulates
      the known A-not-B effects and offers novel predictions that match new
      experimental results. The demonstration supports an embodied view by casting the
      mental events involved in perception, planning, deciding, and remembering in the
      same analogic dynamic language as that used to describe bodily movement, so that
      they may be continuously meshed. We maintain that this mesh is a pre-eminently
      cognitive act of "knowing" not only in infancy but also in everyday activities
      throughout the life span.

PMID- 11515286
TI  - The magical number 4 in short-term memory: a reconsideration of mental storage
      capacity.
AB  - Miller (1956) summarized evidence that people can remember about seven chunks in
      short-term memory (STM) tasks. However, that number was meant more as a rough
      estimate and a rhetorical device than as a real capacity limit. Others have since
      suggested that there is a more precise capacity limit, but that it is only three
      to five chunks. The present target article brings together a wide variety of data
      on capacity limits suggesting that the smaller capacity limit is real. Capacity
      limits will be useful in analyses of information processing only if the boundary
      conditions for observing them can be carefully described. Four basic conditions
      in which chunks can be identified and capacity limits can accordingly be observed
      are: (1) when information overload limits chunks to individual stimulus items,
      (2) when other steps are taken specifically to block the recording of stimulus
      items into larger chunks, (3) in performance discontinuities caused by the
      capacity limit, and (4) in various indirect effects of the capacity limit. Under
      these conditions, rehearsal and long-term memory cannot be used to combine
      stimulus items into chunks of an unknown size; nor can storage mechanisms that
      are not capacity-limited, such as sensory memory, allow the capacity-limited
      storage mechanism to be refilled during recall. A single, central capacity limit
      averaging about four chunks is implicated along with other, noncapacity-limited
      sources. The pure STM capacity limit expressed in chunks is distinguished from
      compound STM limits obtained when the number of separately held chunks is
      unclear. Reasons why pure capacity estimates fall within a narrow range are
      discussed and a capacity limit for the focus of attention is proposed.

PMID- 11515287
TI  - [Physical exercise in the rehabilitation of the coronary patient].
AB  - Coronary patients comprise an heterogeneous population. Many patients, after
      adequate screening, can benefit from physical training, which determines
      hemodynamic changes that are globally useful to the coronary patient. Under
      adequate supervision, physical exercise may help to condition the
      cardiocirculatory system in a favorable way. After successful training, efforts
      require a lower double product. By dumping sharp variations in heart rate and
      blood pressure, an increased margin of safety is obtained, and the coronary
      patient will be able to perform physical activity at a level closer to normal.
      Even without definitive evidence that life expectancy is increased and without
      direct effects on the heart and the coronary arteries, physical exercise promotes
      a better quality of life and decreases the negative impact of the coronary heart
      disease.

PMID- 11515288
TI  - [Prognosis of mitral commissurotomy. Study of 1134 mitral patients 20 years
      later].
AB  - With a test sample (n = 323), consisting of the answers to an inquiry about the
      patients with operated mitral stenosis (n = 1134), between 1952 and 1978, in
      "Hospital Pulido Valente", Lisbon, we compared the group of survivors with the
      decreased in the relation to sex, age, valvular lesion, type of surgery, valvular
      area before and after surgery and existence of incompetence. We concluded that
      mitral stenosis was more frequent in females (4/1), but it had a worse prognosis
      in males. The lower the age at the time of surgery the better long time
      prognosis. Digital and instrumental valvulotomy had similar mortality. Valvular
      incompetence had a worse prognosis and is associated with larger valvular area.

PMID- 11515289
TI  - [Arterial blood pressure behavior during the administration of intravenous
      streptokinase, in patients with acute myocardial infarction].
AB  - OBJECTIVE: To evaluate the effect on blood pressure (BP) of intravenous (i.v.)
      streptokinase (SK) in patients (PTS) with acute myocardial infarction (AMI).
      DESIGN: Retrospective study with analysis of BP registers ten minutes before and
      during SK infusion. SETTING: PTS admitted to the Coronary Care Unit (CCU) of
      Santo Antonio Hospital, Oporto. PATIENTS: Thirty-eight male PTS, average ages of
      54, ranging from 38 to 67, AMI confirmed, and criteria to thrombolytic therapy.
      One patient was excluded on account of persistent hypotension since admission.
      MATERIAL AND METHODS: I.v. infusion of 1.500.000 U of SK over 60 minutes,
      preceded by 200 mg i.v. of prednisolone. BP and heart rate (HR) were evaluated
      with Datascope Accutorr 1A set. The lowest value of the systolic BP (SBP)
      recorded ten minutes before SK infusion was considered the baseline value. We
      valued the reduction of SBP above 15%, defining its fall as the difference
      between the baseline value and the minimum value of SBP recorded during the
      infusion. Hypertension was defined to SBP values below 90 mmHg. MAIN RESULTS: The
      fall was 40.4 +/- 22.1 mmHg (range 9 to 102, having been recorded the minimum
      value at 22.9 +/- 10.9 minutes. It was accompanied by diastolic BP (DBP) fall of
      30.6 +/- 18.9 mmHg (range -2 to 76) and by a HR increasing from 76.2 +/- 13.7
      beats/min. to 80.8 +/- 14.1 beats/min. (p < 0.01). In 86% of the PTS this fall
      was transient, lasting 8.9 +/- 6.3 minutes, and was corrected by slowing or
      stopping the infusion for a few minutes and placing the patient in Trendelenburg
      position. Two PTS needed sympaticomimetic amines because of persistent BP
      reduction despite the previous measures. 92% of the PTS had a SBP fall higher
      than 15% in relation to the baseline value. The SBP was kept over 90 mmHg in 20
      PTS (54%); hypotension was recorded in the remaining 14 PTS (38%), and in 10
      (27%) of these the SBP fell below 80 mmHg. We couldn't prove that the infarction
      and the extension of the ischemic lesion had influenced this BP fall.
      CONCLUSIONS: The BP reduction during treatment with high doses of SK deserves
      some attention because, although transient and easily reversible, it is frequent
      and sometimes significative. It demands then careful monitoring in order to avoid
      the hypoperfusion to the ischemic myocardium, that could jeopardize the potential
      benefits of reperfusion in the reduction of infarction area, the main objective
      of the thrombolytic treatment.

PMID- 11515290
TI  - [Contribution of His bundle electrocardiography for the study of Wolff-Parkinson
      White syndrome].
AB  - In this work particular emphasis is paid to the contribution of His bundle
      recordings associated with atrial pacing to the understanding of the Wolff
      Parkinson-White syndrome. The methodology used for the electrophysiological
      studies is described in detail. The value of this particular type of recordings
      in WPW is demonstrated by the analysis of some illustrative cases which led us to
      a better knowledge of the electrocardiographic changes, and to the separation of
      several patterns of ventricular preexcitation and their relationship to the
      different anatomical pathways postulated for this syndrome. In some instances it
      was possible to caractherize the reentry circuit of reciprocating paroxysmal
      tachycardias and to estimate the refractory periods of the normal and the
      accessory pathways. These later data may be of value for a more rational
      therapeutic approach of the paroxysmal arrhythmias in the WPW syndrome.

PMID- 11515291
TI  - [Thrombolysis in acute myocardial infarction. Remembering Professor Alvaro
      Pimenta. A comment].

PMID- 11515292
TI  - [Atherosclerotic disease --Prevention].

PMID- 11515293
TI  - [Impact of arterial hypertension on organs and systems and its classification].

PMID- 11515294
TI  - [Coronary surgery after 70 years of age].
AB  - Previous reports on coronary artery bypass grafting in elderly patients have not
      usually addressed the current era of aggressive percutaneous angioplasty. To
      investigate this important subgroup of patients, we analyzed our recent coronary
      artery bypass grafting experience with patients 70 years of age or older from May
      1988 to August 1993, 158 consecutive patients in this age range (mean age 70.3
      years) underwent surgical revascularization at our institution. Overall operative
      mortality was 4.4% (7/158), with 71.4% (5/7) of deaths due to cardiac causes.
      Postoperative morbidity occurred in 50.6% (80/158) of patients but was of a
      serious nature in only 12.0% (19/158). Surgical priority was significantly
      correlated with operative mortality: 1.6% (2/122) for elective cases and 17.2%
      (5/29) for urgent or emergency cases (p < 0.01). Univariate analysis isolated the
      need for postoperative inotropic support or mechanical assistance, perioperative
      myocardial infarction and reoperation for bleeding as significant risk factors
      for operative mortality (p < 0.01). Of the patients discharged from the hospital,
      144 (95.4%) were followed up for a mean of 23 months (3-62). During the follow-up
      period there were 3 deaths, all from non cardiac causes, and 92.3% of the
      patients were in Canadian Cardiovascular Society class I (CCS). These results
      indicate that, although with somewhat higher morbidity and mortality rates,
      elderly patients have a very acceptable operative risk in the current era of high
      risk coronary artery bypass grafting, particularly if elective revascularization
      is possible.

PMID- 11515295
TI  - [Effect of vitamin B6, B12 and folic acid levels on basal blood homocysteine
      values and after methionine load].

PMID- 11515296
TI  - [Homocysteine].

PMID- 11515297
TI  - [Surgery of atrial fibrillation with intraoperative radiofrequency].
AB  - Radiofrequency ablation is successful in most supraventricular tachyarrhythmias
      and the first results in percutaneous applications in atrial fibrillation have
      been published. At present, all the surgical techniques for the treatment of
      atrial fibrillation use extensive atrial incisions. A case report is presented of
      a 67 year old woman with chronic atrial fibrillation and rheumatic mitral and
      tricuspid valve disease. At surgery, pulmonary vein isolation was performed using
      a continuous linear ablation around the pulmonary veins, instead of using
      extensive atrial incisions. Concomitantly, a mitral valve replacement and
      tricuspid valve annuloplasty were performed. Five months after surgery the
      patient remains with a stable sinus rhythm surgery and in functional class I
      (NYHA).

PMID- 11515298
TI  - [Autonomic nervous system and cardiovascular system: a paradigm of self
      organization, complexity, and chaos].

PMID- 11515299
TI  - [A case of Ebstein disease and its surgical repair with dura-mater prosthesis].
AB  - The A.A. present a case of Ebstein's Disease, on a woman 48 years old. After
      stressing the clinical and laboratorial aspects, as well as hemodynamics and
      angiocardiography data, they summarize the operation, on which was used a human
      "dura-mater" valve in tricuspid position. There is no knowledge on literature of
      previous applications of this kind of valve on Ebstein's Disease. The patient,
      one year after the operation, is improving quiet well.

PMID- 11515300
TI  - [Computerized electrocardiography system of Porto. I -- General description and
      experience with its use].
AB  - After a brief review of computer assisted ECG interpretation techniques, a
      microcomputer-based system for off-line ECG (Frank) analysis and interpretation
      developed at the University of Porto is presented. The program is menu-structured
      and includes report correction and editing facilities. Clinical data can be
      stored along with the ECG in the individual patient file. More than 500
      characteristics are extracted from the ECG signal by the measurement section of
      the program. The diagnostic section uses Boolean-tree logic. The diagnostic
      threshold values and interpretation statements are kept in an independent file
      and can be changed at any moment by the user. Taking the cardiologist using the
      same logic and criteria as reference standard, an evaluation of the diagnostic
      efficiency of the system was performed in 509 reports from pediatric and adult
      patients: 7% of the reports needed corrections and 113 (3.7%) out of 3070
      diagnostic statements produced had to be changed. Output options include the
      clinical data, more or less extensive listings of the wave measurements, X, Y and
      Z and polar plots and the 12-lead (derived) ECG, besides the interpretation
      report itself.

PMID- 11515301
TI  - [The adventure of Bits].

PMID- 11515302
TI  - Hypertrophic cardiomyopathy. Outflow obstruction is an important feature.

PMID- 11515304
TI  - [Special issue of Revista Portuguesa de Cardiologia].

PMID- 11515303
TI  - [Coronary angioplasty. Initial experience of the Santa Cruz Hospital].
AB  - The initial experience with percutaneous transluminal coronary angioplasty (PTCA)
      at Santa Cruz Hospital is presented. Between May and November 1984, ten patients
      with single significant (> 75%) coronary artery obstructions, 8 of the left
      anterior descending (LAD), 1 of the circumflex (Cx) and one of the right coronary
      artery (RCA), underwent coronary angioplasty using Gruentzig's technique and
      steerable catheters. Five patients were cases of chronic stable angina and 5
      patients were cases of unstable angina, one of them of acute coronary
      insufficiency previously treated with intracoronary streptokinase. In every case
      was possible to cross the lesions which were proximal in 9 cases (7 of the LAD, 1
      of the Cx and 1 of the RCA) and distal (LAD) in one case. Primary failure to
      dilate was seen in 2 cases of unstable angina due to pain and reversible ECG
      changes. In only 1 case there was occlusion at 9 hours after angioplasty which
      required emergency bypass operation. Although with a short follow-up, six
      patients are well and free of symptoms and in only 1 case there was recurrence of
      angina at four and a half months after PTCA. These results which represent the
      beginning of the learning curve are considered satisfactory and rewarding.

PMID- 11515305
TI  - [Study of post-myocardial infarction ventricular aneurysms with equilibrium
      radionuclide angiography. Significance of Fourier analysis].
AB  - The concept of left ventricular aneurysm has been a subject of controversy and
      it's not yet completely settled. This has some implications on the patients
      selection for surgery and explains the various non-invasive methods so far
      developed for the clinical assessment of patients with ventricular aneurysms.
      Seventy-one patients with ischemic heart disease, 65 with recent myocardial
      infarction, were studied by equilibrium radionuclide angiography (ERNA) in order
      to define left ventricular wall motion abnormalities. One hundred ERNA were
      undertaken, through the usual erytrocites in vivo labelling technic, employing a
      GE 400 T Gama-Camera GP. Image acquisition was through 400 cardiac cycles, on LAO
      (30 and 60 degrees) and left lateral. PAGE protocol was employed. Fourier
      transform was used in the present work to obtain phase and amplitude images,
      which actually became the main criteria to define aneurysmatic areas. Global
      ejection fraction, regional wall motion and regional ejection fraction were other
      parameters investigated. Wall motion abnormalities have been identified in all
      the 65 patients having suffered a myocardial infarction. Extensive areas of
      akinesia or localized dyskinesia were present in 40 patients (16.5%), while
      remainder 25 had just localized hypoakinesia. Phase image enabled the selection
      of LV areas of contraction delay in 19 of the 40 patients with extensive wall
      motion abnormalities (Group I). In such Group I we could identify an LV area with
      contrasting colour, defining the aneurysmatic LV portion. In the order 21
      patients with extensive akinesia, no significant changes of colour were present
      on ventricular phase image (Group II) meaning absence of aneurysm. No phase
      disturbances were seen in the remainder 25 patients with MI (Group III) and the 6
      patients with CAD without MI had normal phase images (Group IV). The percentage
      of akinetic segments was 39.1 and 35.4 in Group I and II, respectively (p = .53)
      while it was significantly lower in Group III 17.9%; p < .0001). LV ejection
      fraction was statistically different in the four groups considered (I = 30.0% +/-
      3.7; II = 39.9% +/- 2.9; III = 49.0% +/- 2.5; IV = 62.0% +/- 3.2). The degree of
      phase delay in aneurysmatic zones was quantified by the phase histogram. Average
      value of phase for the left ventricle was 129.7 +/- 8.4 degrees, and for the
      aneurysm it was 238.0 +/- 5.0 with an average phase delay of 104.8 +/- 4.1
      degrees. The association of phase and amplitude images and the measurements of
      phase and amplitude values on the histograms allowed the distinction of akinetic
      aneurysm (phase delay and low amplitude) from the dyskinetic aneurysms (phase
      delay and high amplitude). Half of the isotopic diagnosis of aneurysms have been
      confirmed by classic contrast angiography, and a third of then have undergone
      surgery. The two dyskinetic aneurysms that have been submitted to aneurysmectomy
      had pos-operative improvement of LV function. On summary, phase and amplitude
      analysis by the Fourier method, which is independent of LV geometry, showed that
      LV regions with high phase values are associated with severe regional wall motion
      abnormalities and low ejections fractions. The definition of the sequence and
      amplitude of ventricular contraction allows the distinction of akinetic and
      dyskinetic aneurysms, anticipating the method as a valid contribution for the
      screening of patients likely to benefit from aneurysmectomy.

PMID- 11515306
TI  - [Neuro-hormonal mechanisms in heart failure -- from physiopathology to
      treatment].
AB  - This review updates some recent advances of a new and exciting developments in
      basic and clinical cardiology: a) the role, in the congestive heart failure
      (CHF), of the neurohumoral systems (NHS) which act to maintain circulatory
      homeostatic equilibrium, and b) the therapeutic implications of such a role. Six
      NHS, acting in CHF, have presently been identified: three of them induce
      vasoconstriction and sodium retention (sympathetic nervous systems, renin
      angiotensin-aldosterone system and arginine-vasopressine system); the remaining
      three offset or balance the former ones, acting, therefore as "counterregulators"
      (prostaglandins--PGE2 and PGI2--, dopaminergic system and atrial natriuretic
      factor). Each one of these NHS influences the "compensatory" mechanisms of heart
      failure, acting on the target-organs both by direct effects and by interaction
      with other NHS; consequently, in heart failure, all the NHS are stimulated with
      the respective increase in the plasma levels of their active agents. In
      asymptomatic stages of ventricular dysfunction the stimulation of the vasodilator
      and-natriuretic systems appears to be predominant and able to maintain
      circulatory equilibrium. However, as the heart dysfunction increases and becomes
      symptomatic, the vasoconstrictor and sodium-retaining forces appear to
      predominate; this phenomenon becomes increasingly apparent as the functional
      class becomes more advanced. The hyperstimulation of these last systems has an
      extremely important role in the pathophysiology and clinical manifestations of
      congestive heart failure, as well as in its prognosis. Therefore, the attempts to
      correct these neurohormonal imbalance in patients with heart failure has a sound
      rational basis, not only to improve the symptoms and the exercise capacity but
      also to increase the survival of these patients. At the present time, amongst the
      potential pharmacological interventions acting on NHS in CHF, the blockade of the
      RAA system with ACE-inhibitors is generally accepted as the most feasible, the
      safest and the most effective therapeutic tool. In fact, its application has
      broadened from an earlier use in severe CHF to other symptomatic stages of
      cardiac failure, including the milder forms. In addition, preliminary data
      strongly suggest its unique usefulness in asymptomatic phase of ventricular
      dysfunction. Looking back at the medical therapy of heart failure, in can be
      concluded that we are starting a new era. Throughout 200 years (since the
      introduction of digitalis) the therapeutic goal in CHF has been the improvement
      of symptoms. With the developments of the present decade, a new and exciting goal
      is being offered to these patients, called by Packer "the second frontier", that
      is, the prolongation of their lives.

PMID- 11515307
TI  - Ultrastructural and molecular changes in the left and right ventricular
      myocardium associated with ascites syndrome in broiler chickens raised at low
      altitude.
AB  - The present study examines ultrastructural and molecular changes in ventricular
      myocardium associated with ascites cases in fast-growing broilers raised at low
      altitude. Extensive ultrastructural lesions were seen in the left and right
      ventricular myocardium of broilers with fulminant heart failure and ascites.
      Significant changes included lesions in the myofibril contractile apparatus,
      altered mitochondria, marked reduction in the myofibril component, and changes in
      the extracellular matrix (ECM) architecture. No lesions were observed in hearts
      of slow growing broilers, but mild to moderate changes (predominantly in the left
      ventriculum) were apparent in the hearts from some clinically normal, fast
      growing broilers. SDS-PAGE profiles of washed myofibrils showed several
      distinctly different bands in preparations from left ventricular myocardium of
      ascitic birds. Western blot analysis of these samples revealed several fragments
      of myosin heavy chain, M-protein, and titin. Based on gelatinolytic activity,
      matrix metalloproteinases (MMP) in the cytosolic fraction of ventricular
      myocardium homogenates were identified as MMP-2. The relative activity of this
      enzyme appears to be considerably higher in preparations from broilers,
      particularly in the preparations from the left ventriculum of fast-growing
      broilers, in comparison to leghorns or slow growing broilers. The nature and
      distribution of the changes in the heart indicate that chronic cardiomyopathic
      process in the left ventricular myocardium occurs during the development of
      ascites. It is postulated that progressive deterioration of the left heart pump
      function caused by initial lesions in the left ventricular myocardium is a
      significant factor in the development of pulmonary hypertension and the
      pathogenesis of ascites in broilers raised at low altitude.

PMID- 11515308
TI  - Comparison of three different techniques for subcutaneous relocation of the
      carotid artery in small ruminants.
AB  - Three surgical techniques for subcutaneous relocation of the carotid artery in
      small ruminants are compared. A total of 25 sheep and seven goats were used and
      randomly assigned to three groups. In group A (technique A), the carotid artery
      was moved subcutaneously and kept there by suturing the tissues on both sides of
      the jugular vein beneath the relocated artery and the skin above it. In the other
      two groups the relocated artery was secured into a skin strip (technique B) or a
      skin fold (technique C). The animals were used for repeated blood sampling over a
      period of several months. Technique A did not provide good immobilization whilst
      among the three, technique B provided the least protection of the relocated
      artery and was the most difficult to perform. It was concluded that technique C
      was superior to the other two methods in providing better conditions for long
      term blood sampling.

PMID- 11515309
TI  - Clinical signs and diagnosis of scrapie in Italy: a comparative study in sheep
      and goats.
AB  - This article reports the clinical signs of scrapie occurring in sheep-goat flocks
      in Italy. The research, carried out on over 500 goats and 550 sheep, yielded an
      interesting clinical picture, especially of goat scrapie. The affected animals,
      aged between 2 and 8 years, showed neurological signs that could be classified
      into three categories: changes in mental status, abnormalities of movement and
      changes in sensation. Some general clinical signs were also observed. The
      clinical suspicion was confirmed by histopathological and biochemical
      investigations.

PMID- 11515310
TI  - Evaluation of the oxidative stress in growing pigs by microplate assays.
AB  - The ability of pigs to neutralize the reactive oxygen species (ROS) plays a key
      role in their welfare. Two micromethods were developed to evaluate the oxidative
      stress and the anti-oxidative response in sera. We tested these methods for
      linearity, repeatability and reproducibility. A hydroxyl radicals (HR) test,
      based on the Fenton reaction, showed a linearity between 0.26 and 4.5 mM H2O2 (r
      = 0.997), with a coefficient of repeatability (CVr) of 1.9 and a coefficient of
      reproducibility (CVR) of 2.9. An anti-oxidant power (AOP) test, based on the
      capability of sera to neutralize a titred hypochlorous acid solution (HClO),
      showed a linearity between 55 and 880 microM HClO neutralized (r = 0.984), with
      CVr = 3.1 and CVR = 4.9. We assessed the applicability of such tests in field
      conditions on three different farms. Farm A recorded a positive anamnesis of
      Mulberry heart disease. Dietary Vitamin E supplementation was given at 50 p.p.m.
      in farms A and B and at 150 p.p.m. in farm C, respectively. The group from farm A
      showed HR sera levels higher than those of farm B and farm C (farm A, mean =
      31.61 +/- 2.87 mM H2O2, n = 10; farm B, 28.53 +/- 2.30, n = 10; and farm C, 25.63
      +/- 1.03, n = 10; P < 0.01). The AOP test was not able to discriminate between
      farms. The AOP levels found (mean = 472.50 microM HClO neutralized: n = 30)
      probably represent the maximum response of the organism to compensate the
      oxidative stress. HR and AOP are stable in sera stored at +4 degrees C. We
      discuss the application of such methods for the assessment of farmed animals'
      welfare.

PMID- 11515311
TI  - Effects of fat feeding and energy level on plasma metabolites and hormones in
      Shetland ponies.
AB  - The aim of this study was to investigate the influence of a fat-supplemented diet
      compared with a carbohydrate diet on the lipid metabolism and the enteroinsular
      axis of Shetland ponies. The 'crossover' experiment was divided into two parts:
      in the first 10 weeks the diets comprised the correct number of calories
      according to requirements and in the following 10 weeks they were hypercaloric,
      in order to check the effect of a different energy content of the diets. Feeding
      the fat-enriched diet, independently of its energy content, led to a significant
      decrease in plasma triglycerides, associated with a mean 50% increase of plasma
      lipoprotein lipase activity. After oral glucose load the ponies on fat-enriched
      diets showed higher plasma glucose concentrations. Oral glucose administration
      after feeding the hypercaloric fat-enriched diet led to a 25-fold increase of
      plasma insulin levels. Glucose-dependent insulinotropic polypeptide plasma levels
      were increased in the animals on the fat-enriched diets. The results of this
      study suggest that fat feeding improves triglyceride clearance. However, the fat
      supplementation of the diet also led to impaired glucose tolerance. These results
      are important for a better understanding of the function of the enteroinsular
      axis. To investigate the influences of fat on lipid metabolism in relation to the
      aetiopathogenesis of equine hyperlipaemia further studies involving diseased
      animals are needed.

PMID- 11515312
TI  - Immunohistological demonstration of erythroid cells in canine bone marrow.
AB  - In an immunohistological/cytological study of canine bone marrow, the aim was to
      demonstrate canine erythroid cells with the help of various commercially
      available antibodies against human antigens (monoclonal antibody against
      glycophorin A, polyclonal antibodies against haemoglobin and spectrin). In order
      to preserve possible cross-reacting epitopes various fixation methods (cross
      linking, precipitating and dehydrating fixing agents, partly in combination with
      unmasking measures), decalcification techniques [acid or
      ethylenediaminetetraacetic acid (EDTA) decalcification] and tissue-embedding
      methods (paraffin embedding, cryostat sectioning technique) were used.
      Alternative methods, such as the preparation of cell smears and immunoblotting,
      were also employed. The only result that was of use for routine diagnostic
      procedures (paraffin sections) was that obtained by using polyclonal antibodies
      against haemoglobin. Best results were achieved when tissue was fixed in a
      formaldehyde-glutaraldehyde mixture, decalcified in EDTA and treated with
      microwave irradiation. The primary antibody was used in a dilution of 1:500 and
      incubated for 16 h. With the exception of mature red blood cells and
      proerythroblasts, different stages of erythrocytopoietic cells in canine bone
      marrow were shown to be arranged in erythrons. The polyclonal antibody against
      spectrin also showed clear cross-reactivity, but was only employable in other
      systems (immunoblotting). The monoclonal antibody against glycophorin A reacted
      only when used on human tissue or cells.

PMID- 11515313
TI  - Investigation of biochemical and haematological side-effects of enrofloxacin in
      dogs.
AB  - In the present study, effects of enrofloxacin on biochemical, haematological and
      blood gas parameters were investigated. Changes in laboratory parameters were
      monitored during the treatment period. Enrofloxacin was administered (5 mg/kg
      intramuscularly, once daily) to 10 healthy dogs for 14 days. Acidosis and
      temporary increases in aspartate aminotransferase, indirect bilirubin, sodium,
      partial pressure of CO2 and mean corpuscular volume levels as well as decreased
      levels of inorganic phosphorus, ionized calcium, potassium, partial pressure of
      O2 and standard bicarbonate were observed. The results of this study suggest that
      these observed effects of enrofloxacin on blood gas parameters should be taken
      into consideration in long-term use of the drug.

PMID- 11515314
TI  - Aggressive behavior in combat veterans with post-traumatic stress disorder.
AB  - The incidence of aggression and violent behavior in combat veterans varies and
      can be observed with regard to the presence or absence of post-traumatic stress
      disorder (PTSD). Significantly greater occurrence of aggression was observed in
      combat veterans with PTSD compared with those without PTSD. There are various
      types of aggressive behavior that frequently are combined. Autoaggressive
      (suicidal) and heteroaggressive (interpersonal violence) behaviors predominate,
      with dominating verbal aggression and impulsive somatic reactions. Impulsive
      reactions are more frequently directed toward unknown persons, whereas verbal
      aggression is mostly aimed at known people. In the occurrence of aggressive
      behavior in combat veterans with PTSD, important roles are played by education
      level, low socioeconomic status, maltreatment in childhood, and previous types of
      violent behavior (before participation in war events).

PMID- 11515315
TI  - Assessment of post-traumatic stress disorder and comorbidity.
AB  - The symptoms of lifetime post-traumatic stress disorder (PTSD) and comorbid
      diagnoses were compared among 502 combat-experienced soldiers under examination
      for compensation-related purposes to confirm or deny the diagnosis of PTSD and
      196 soldiers with combat experience without any psychiatric disorder. The two
      groups were matched with regard to duration of combat experience, time between
      combat experience and the study, age, marital status, and education. PTSD was
      diagnosed by psychiatrists with a structured clinical interview according to the
      research version of the International Classification of Diseases and the
      Diagnostic and Statistical Manual of Mental Disorders. The psychologists applied
      the Mississippi Scale for Combat-Related PTSD, Watson's criteria for PTSD, the
      Minnesota Multiphasic Personality Inventory version 201, and the Trauma
      Questionnaire. Also, a very detailed heteroanemnestic questionnaire was completed
      by social workers. Medical documentation and data from the combat services were
      provided during the examination for compensation-related purposes. After
      psychiatric and psychological assessment, 20% of the combat-experienced soldiers
      under examination for compensation-related purposes were diagnosed with lifetime
      PTSD, 47% were diagnosed with PTSD and comorbid disorders, 6% were diagnosed with
      PTSD and enduring personality change, and 5% were diagnosed with adjustment
      disorder. Twelve percent did not fulfill any diagnostic psychiatric criteria, and
      10% fulfilled diagnostic criteria for other psychiatric disorders, although they
      had previous medical documentation confirming PTSD diagnoses. Correlation
      coefficients between psychiatric and psychological assessment were significant,
      indicating their complementarity in reaching the final diagnosis. It is necessary
      to include many different assessment methods in the examination for forensic or
      compensation-related purposes to obtain a more objective assessment.

PMID- 11515316
TI  - Relationship between morbidity and body mass index of mariners in the Japan
      Maritime Self-Defense Force Fleet Escort Force.
AB  - To establish a practical weight management program for mariners in the Japan
      Maritime Self-Defense Force (JMSDF) Fleet Escort Force, the relationship between
      morbidity and body mass index (BMI) was studied. To estimate morbidity, 10
      medical problems were used as indices (hyperlipidemia, hyperuricemia, diabetes
      mellitus, lung disease, heart disease, upper gastrointestinal tract disease,
      hypertension, renal disease, liver disease, and anemia). A curvilinear
      relationship was found between morbidity and BMI, in which a BMI of 17.5 was
      associated with the lowest morbidity. This curvilinear pattern was more complex
      than a curve reported previously for Japanese civilians. Using the present curve
      and aiming for a BMI of 17.5 will help in the design and implementation of a
      practical management program for health promotion in the JMSDF.

PMID- 11515317
TI  - Medic for the millennium: the U.S. Army 91W health care specialist.
AB  - The new millennium challenges the Army Medical Department to provide good care in
      a variety of circumstances from peacetime to operations other than war to combat.
      To provide care in this broad variety of missions, the Army Medical Department
      needs flexible providers. The new 91W health care specialist enlisted medic is
      designed to meet this need. By coupling skills in emergency care, evacuation,
      medical force protection, and primary care with certification in emergency
      medical technology, the 91W initiative will fill the needs of the Army now and
      into the new millennium.

PMID- 11515318
TI  - Substitute ellipse of the permanent cavity in gelatin blocks and debridement of
      gunshot wounds.
AB  - A new method in terminal ballistics is presented that allows precise numerical
      analysis of characteristics of the permanent cavity by computed tomography (CT).
      Shots were made with a Russian AK-74 assault rifle (5.45 mm) into gelatin used as
      a tissue simulant. CT scans were made of the gelatin blocks, transferred into
      digital format, and analyzed using computer software. CT scans of the permanent
      cavity are characterized by markedly irregular shapes, and an attempt was made to
      simplify these forms and to link them with surgical debridement of gunshot
      wounds. An assumption was made that the zone of debridement has the form of an
      ellipse. Using the information from the CT images, a substitute ellipse was
      constructed as an approximation of the a vital tissue surrounding the wound
      channel with the aim of approaching a more exact definition of the zone of
      necessary debridement of gunshot wounds.

PMID- 11515319
TI  - Early resuscitation with hypertonic saline/dextran in uncontrolled intra
      abdominal bleeding in swine combined with a soft tissue gunshot wound.
AB  - The effects of hypertonic saline/dextran (HSD) on hemodynamics and on rebleeding
      were studied during an uncontrolled intra-abdominal hemorrhage combined with a
      high-energy gunshot wound (GSW) in the hind limb of anesthetized swine. The GSW
      had instant effects on the central hemodynamics, which were aggravated when the
      internal hemorrhage was induced. Compared with baseline, cardiac output decreased
      to about 42%, mean arterial pressure decreased to 52 +/- 4%, and mean flow rates
      in the splanchnic region, in the upper aorta, and in the kidney decreased to 51
      to 15%. The injection of HSD at 10 minutes was followed by a prompt increase in
      blood flow rates, but rebleeding occurred in five of eight animals, although only
      two died. In conclusion, GSW induced instant changes in hemodynamics at distance
      from the injury. When HSD treatment was given in a bolus injection, rebleeding
      occurred in five of eight animals, although the second hemorrhage became fatal in
      only one animal.

PMID- 11515320
TI  - Pharmaceutical stability as it relates to climatic exposure.
AB  - Manufacturers' recommended temperatures for pharmaceuticals were compared with
      actual field temperatures that the medications were exposed to during the winter
      months of December and February in the Republic of Korea. Two daily temperatures
      of field pharmaceuticals were taken in a M577 armored aid station. These
      temperatures were then averaged and compared with the ambient high and low for
      that day. The total data collected during the month of December yielded a mean
      pharmaceutical temperature of 57.50 degrees F with a standard deviation of 5.37.
      This result showed that the heating unit in the M577 was able to keep the
      medications 15.07 degrees F warmer than the mean high and 30.77 degrees F warmer
      than the mean low for the temperatures collected. For February, the mean
      temperature of pharmaceuticals was 49.25 degrees F with a standard deviation of
      5.89. This temperature was 11.37 degrees F higher than the mean high and 33.00
      degrees F higher than the mean low. For both the months of December and February,
      the heating unit in the vehicle tested was not able to meet manufacturer's
      specifications for more than 90% of the medications reviewed.

PMID- 11515321
TI  - War injuries of the talus.
AB  - Twenty-eight patients with war fractures of the talus were reviewed to determine
      the incidence of infection and late functional results. The average age of our
      patients was 37.5 years. Twenty-one injuries were explosive fractures that
      resulted from shell fragments or mines; seven fractures resulted from gunshot
      missiles. Seven patients had isolated talus injuries, whereas 21 patients had
      associated fractures of other bones of the foot or lower leg. All patients were
      initially treated with debridement, tetanus immunization, intravenous
      antibiotics, and stabilization, either with cast immobilization or an external
      fixator. Five days after injury, wound cultures were positive in 25 of 28 feet.
      Infection was eventually eradicated in all patients, allowing for soft tissue
      coverage. One patient eventually required a below-knee amputation. The patients
      were reviewed for functional outcome at 36 to 60 months after injury. Most
      patients reported a certain degree of residual complaints. The overall result can
      be considered excellent in only one patient.

PMID- 11515322
TI  - Volatile anesthetics give a false-positive reading in chemical agent monitors in
      the "H" mode.
AB  - Chemical agent monitors (CAMs) are routinely used by the armed forces and
      emergency response teams of many countries for the detection of the vesicant
      sulfur mustard (HD) and the G series of organophosphate nerve agents. Ambient
      operating room isoflurane levels were found to produce strong positive signals in
      the "H" mode when the CAM was used to monitor the efficacy of decontamination
      procedures during routine surgical procedures on HD-poisoned animals requiring up
      to 8 hours of general anesthesia. Subsequent testing showed that isoflurane, as
      well as desflurane, sevoflurane, halothane and methoxyflurane, produce two
      ionization peaks in the CAM response. One of these peaks is interpreted by the
      CAM processing software as HD, resulting in a CAM "H" mode bar response. No
      interference was encountered with isoflurane, desflurane, and sevoflurane when
      the CAM was set to the "G" mode, although extremely high (nonclinical)
      concentrations of halothane and methoxyflurane yielded a weakly positive bar
      response. These findings have potentially serious ramifications for the medical
      management of patients resulting from terrorist, military, or chemical agent
      decommissioning activity when concomitant chemical injuries are also possible.

PMID- 11515323
TI  - A model for self-directed learning in a military facility.
AB  - Continuing education for health care providers presents an ongoing challenge in
      an environment of personnel limitations and budget constraints. Learning is a
      constant requirement for safe and effective health care practice; in addition, it
      is often a requirement for licensure. The purpose of this article is to review a
      model of distance learning as a method of education to meet the needs of a
      multidisciplinary staff, applicable to all services and types of personnel. The
      model was implemented in the Department of Nursing at Madigan Army Medical
      Center. The results were deemed highly successful after 1 year, considering the
      large number of contact hours completed and the relatively low cost invested. The
      conclusion indicates that distance learning provides a high level of knowledge
      attainment available 24 hours a day, even at remote military settings and
      outlying facilities.

PMID- 11515324
TI  - Basic recruit training: health risks and opportunities.
AB  - The present review examines the impact of basic recruit training on health and
      lifestyle. Many of those recruited begin training with a less than optimal
      lifestyle with respect to fitness, smoking habits, alcohol consumption, drug
      abuse, and exposure to sexually transmitted diseases. Thus, there is scope to
      enhance training programs that address fitness and lifestyle, minimizing
      potential losses in health and efficiency from upper respiratory infections,
      musculoskeletal injuries, cardiac catastrophes, mental disturbances, and adverse
      responses to extreme environments.

PMID- 11515325
TI  - Preassignment examination for personnel on Iwo Jima.
AB  - The Japan Maritime Self-Defense Force (JMSDF) requires all personnel assigned to
      Iwo Jima to undergo a preassignment medical examination. The efficacy and benefit
      of this mandatory examination has not been evaluated objectively in depth. Our
      purpose was to review the health status of JMSDF personnel assigned to Iwo Jima
      and to evaluate the correlation of the preassignment medical examination to their
      current health status for the study period. We divided the participants into two
      groups. Group Y was composed of JMSDF personnel receiving a preassignment medical
      examination, and group N was composed of those personnel who did not receive the
      examination. After the annual health examination, health status was evaluated
      using objective criteria. We found little statistically significant difference
      among group Y and group N participants. However, proportionally more patients
      currently receiving care for or diagnosed with hypertension, hyperuricemia, or
      severe obesity were identified as being members of group N than group Y. We have
      demonstrated that the preassignment medical examination may contribute to
      predicting the health status of potential Iwo Jima personnel and may contribute
      to controlling the cost of care associated with these specific diagnoses by
      limiting the assignment of at-risk personnel.

PMID- 11515326
TI  - The rotary pursuit test is not an index of normal psychomotor function in humans.
AB  - OBJECTIVE: This study sought to assess whether the rotary pursuit test is a good
      indication of the psychomotor performance of human subjects during normal working
      hours. Circadian hormonal profiles of salivary melatonin and cortisol were also
      established for correlation with performance. METHODS: Ten healthy individuals
      working in the Department of Obstetrics and Gynecology laboratory participated in
      this study. The experiment was conducted during a normal 8.5-hour working day in
      which routine laboratory tasks such as running radioimmunoassays were performed.
      Saliva samples were collected every 2 hours starting at 8:00 a.m. Simultaneously,
      self-rated questionnaires on mood states, sleepiness, stress, and types of food
      and drinks consumed were also recorded. At 10:00 a.m., 12:00 noon, 2:00 p.m., and
      4:00 p.m., the subjects' were tested on the rotary pursuit machine, on which
      their ability to track a rotating target with a stylus was tested by means of
      measuring the time the stylus stays on target. RESULTS: The circadian profiles of
      salivary melatonin and cortisol were similar to what previous studies have shown.
      Increases in cortisol levels were associated with food intake, work stress, or
      spontaneous awakening. Tracking performance (time on target) improved
      significantly from 10:00 a.m. to 2:00 p.m. and then decreased nonsignificantly at
      4:00 p.m. only at the speed setting of 60 rpm. There was no correlation between
      the three parameters measured. SUMMARY: Variation of psychomotor performance
      during a normal working day and in noncircadian disrupted individuals cannot be
      measured by the rotary pursuit test. Furthermore, a learning effect could mask
      any variation in performance.

PMID- 11515327
TI  - Blue rubber bleb nevus syndrome: a case report with long-term follow-up.
AB  - Blue rubber bleb nevus syndrome is an uncommon condition manifested by
      gastrointestinal and skin hemangiomas that lead to gastrointestinal bleeding and
      anemia. The purpose of this report is to present a case with long-term follow-up.
      The patient is a 37-year-old female with a life-long history of blue rubber bleb
      nevus syndrome. She underwent multiple resectional operations that combined to
      give her a partial gastrectomy, partial small bowel resection, total abdominal
      colectomy, and end ileostomy. She continues to need endoscopy with sclerotherapy.
      In addition, she has iron-deficiency anemia, nephrolithiasis, major depression,
      and malnutrition despite vitamin and caloric supplements. There are no other
      reports showing these complications of blue rubber bleb nevus syndrome or with
      this length of follow-up. Therapy for blue rubber bleb nevus syndrome should be
      conservative if possible, because operative therapy may lead to significant long
      term complications.

PMID- 11515328
TI  - The latency between traumatic axonal injury and the onset of amyotrophic lateral
      sclerosis in young adult men.
AB  - Traumatic axonal injury-induced apoptotic motor neuron cell death in neonatal
      rats is an established animal model used to study potential therapeutic agents in
      amyotrophic lateral sclerosis (ALS). In an analogous manner, trauma causing motor
      neuron axonal injury (which included focal neuropathy, plexopathy, and
      radiculopathy) preceded the onset of ALS in nine young adult men (age range, 28
      43 years). The latency between the traumatic axonal injury and the onset of ALS
      symptoms in these patients ranged from 5 to 42 months (mean, 14.6 months).

PMID- 11515329
TI  - Recurrent infectious mononucleosis caused by Epstein-Barr virus with persistent
      splenomegaly.
AB  - We present the clinical case of a 20-year-old male soldier who appeared in
      general good physical condition. He suffered from infectious mononucleosis caused
      by Epstein-Barr virus that had recurred 2 years after the first serologically
      documented episode. The detected splenomegaly persisted in the healthy young man,
      who otherwise showed no apparent immune deficiency. To our knowledge, this is an
      extremely rare condition.

PMID- 11515330
TI  - Using computer graphics to preserve function in resection of malignant melanoma
      of the foot.
AB  - The increasing incidence of malignant melanoma challenges physicians to find
      innovative ways to preserve function and appearance in affected areas that
      require partial resection. We carefully planned the resection of a malignant
      lesion between the third and fourth toes of a 77-year-old man with the aid of
      computer technology. The subsequent excision of the third, fourth, and fifth
      digits was executed such that the new metatarsal arc formed would approximate the
      dimensions of the optimal hyperbola, thereby minimizing gait disturbance.

PMID- 11515332
TI  - [Humanitarian medicine: a question of principle].

PMID- 11515331
TI  - [More services or better services? Quality and efficiency of hospital services
      for elderly people].

PMID- 11515333
TI  - [The bioethics challenge of equity: its significance in public health].
AB  - This paper presents the bioethical discourse as a stimulus to dialogue between
      beliefs, ideologies, rationalities, and persons. Among its dominant themes, it
      may be distinguished between those related to communities and those related to
      individuals. Although equity belongs into the former, it finds expression in
      individual life as solidarity and empathy. It is possible to formulate guidelines
      for research in social science and epidemiology distinguishing between values,
      principles and behavior rules, which find expression in the notion that
      bioethical reflection must anticipate challenges and dangers and not simply
      respond to technoscientific developments.

PMID- 11515334
TI  - [Process re-engineering in public hospitals: re-inventing of the wheel?].
AB  - The purpose of this paper is that of analyzing the hypothesis that, as originally
      stated by its creators, the reengineering methodology for the improvement of
      efficiency and productivity, cannot be successfully implemented in Spanish public
      hospitals, and in fact, the so called experiences do not keep with the basics of
      such an approach. The technique employed for this study consisted, on one hand,
      of reviewing and comparing the literature published on this subject and, on the
      other, on experimentation by means of a case study conducted at a public hospital
      for the purpose of testing out the outlined hypothesis. The review and comparison
      of works previously published on this subject revealed that the technique for
      improving on-the-job efficiency according to the theory-based concepts of the
      process reengineering approach is not adaptable to public hospitals in Spain. The
      case study supported this finding, additionally highlighting the fact that in
      order for any relatively major changes in the working processes at public
      hospitals to be recommended, a number of organizational and human factors must be
      taken into consideration as aspects involved regardless of the methodological
      approach taken. The indiscriminate implementation in public hospital
      administration of trends currently fashionable in the business administration
      field may defeat its own purpose if these trends are not previously evaluated
      prior to being implemented. An assessment must first be made as to their being
      suited to the intended purpose.

PMID- 11515335
TI  - [Review of scientific evidence on alternatives to methadone in the
      psychopharmacologic treatment of opiate dependence].
AB  - The implementation of the methadone maintenance treatment programs marked a true
      milestone in the treatment of those opioid-dependent patients who had met with
      failure in the different treatment alternatives which had existed up until that
      time. The purpose of this paper is that of reviewing the scientific evidence
      regarding the advantages and drawbacks involved in the different drug-related
      alternatives for use in lieu of methadone for opioid-dependent individuals. To
      pinpoint the clinical tests conducted, searches were run on Medline (1966-1999),
      the IDIS (Iowa Drug Information System (1985-1999) and the Cochrane Library 1999
      clinical testing database (3rd quarter). Screening and summarization of the
      literature. Based on the review made, the conclusion was reached that methadone
      is the chosen drug in substitution treatment for opiate-dependent patients. LAAM
      came forth as an alternative to methadone for stable patients not requiring close
      monitoring, although marketing approval was suspended at the recommendation of
      the Scientific Committee of the European Agency for the Evaluation of Medical
      Products as of March 2001. Buprenorphene may be one alternative to methadone,
      however the optimum dosage pattern is as yet unknown. Heroine is the alternative
      studied to the least degree, although the highly limited number of existing
      studies indicate that this could be a useful alternative for heroine addicts for
      whom other maintenance treatments have failed.

PMID- 11515336
TI  - [Measurement of body fat with bioelectric impedance, skinfold thickness, and
      equations based on anthropometric measurements. Comparative analysis].
AB  - BACKGROUND: There is growing clinical interest in estimating body fat percentages
      (%FM). The aim of this study was a comparison of body fat measurement by
      anthropometric equations, skinfold thickness (SFT) and bioelectrical impedance
      (BIA) methods. METHODS: Cross-sectional study. 149 healthy individuals (83 males
      and 66 females) were recruited. Height, weight, waist circumference, skinfold of
      biceps, triceps, subscapular and suprailiac regions, sum and log10 sum of four
      folds were obtained. %FM were calculated using the Siri equation (for sex or age
      sex), Brozeck (sex or age-sex), Deurenberg, Lean and segmental BIA (Omron BF
      300). Methodological differences among the various methods were analyzed with
      Spearman (SCC) and intraclass (ICC) correlation coefficients and Bland-Altman
      method. The reference method is the Siri-age-sex equation. RESULTS: The means of
      %FM were 26.8 +/- 8.3% (Siri-age-sex), 25.7 +/- 8.1% (Siri-sex), 25.97 +/- 7.6%
      (Brozeck-age-sex), 24.9 +/- 7.5% (Brozeck-sex), 25.6 +/- 8.8% (BIA), 28.6 +/-
      8.2% (Deurenberg), 29.7 +/- 8.2% (Lean-waist circumference) and 29.4 +/- 9.3%
      (Lean-triceps-waist). The %FM values for all methods were highly intercorrelated
      (all SCC > 0.83 and CCI > 0.85). Brozeck-age-sex (average difference 0.8%; limits
      of agreement -0.48 to 2.08%) and BIA (1.17%; -6.21 to 8.55%) show the best
      agreement according to Bland and Altman analysis with Siri-age-sex equation.
      CONCLUSIONS: Deurenberg and Lean equations provide different body fat mass
      estimates than those derived from SFT measurement and BIA and thus should not be
      used interchangeably. The use of Siri-Brozeck equations is recommended for %FM
      assessment. The results suggest that segmental BIA-Omron BF 300 may be a valid
      alternative method.

PMID- 11515337
TI  - [Factors associated with the use and adaptation of hospitalization in people over
      than 64 years of age].
AB  - BACKGROUND: Some social, medical or functional aspects are associated with a
      greater use of health care resources, although this does not necessarily imply an
      inappropriate usage of the same. The aim of this research is that of ascertaining
      the influence of health condition on hospital stays and inappropriate stays among
      the population over 64 years of age. METHODS: A cohort representative of the
      population over age 64 in the Judicial District of Toledo (n = 3214) whose health
      condition had been previously evaluated was studied over an eighteen-month period
      identifying the income and length of stays at the public hospitals, the
      appropriateness of which was evaluated by the Appropriateness Evaluation
      Protocol. Associations analyzed were those of the cohort socio-demographic
      characteristics, health condition-related variables and morbidity with frequency
      and hospitalization rates and with inappropriate stays and admissions. RESULTS:
      During the 18 months of study 410 individuals were hospitalized, who generated
      546 admissions (frequency rate = 17.0 admissions/100 rooms) and 7015 stay days
      (hospitalization rate = 218.3 stays/100 rooms), 18.9% of the admissions and 49.9%
      of the stays were evaluated as inappropriate. Hospitalization was associated with
      a worse health condition, institutionalization, male sex, certain pathologies and
      previous health services usage. Patients characteristics were not associated with
      the percentage of inappropriate stays. 97.5% of inappropriate stays were
      attributed to hospital scheduling problems and physicians' practices.
      CONCLUSIONS: Socio-demographic factors, morbidity, health condition and previous
      health service usage are shown as good hospitalization predictors for senior
      citizens, but these factors are not related to inappropriate hospitalization
      usage.

PMID- 11515338
TI  - [Groups of resource utilization in acute care units and average length of stay at
      geriatrics services].
AB  - BACKGROUND: In recent years, Patient Classifications Systems (PCS's) have been
      implement in Spain for the purpose of gauging the "hospital product". However,
      the most conventional systems are not very well-suited to the senior citizen
      population, among whom illness-related disability is a determining factor with
      regard to explaining the usage of resources and the results of the health care
      provided. Therefore, the idea was brought forth of implementing a system in units
      providing senior citizen care which would entail this parameter, that is, the
      Resource Usage Groups (RUG's), analyzing the characteristics and differences in
      the RUG-related spread in four Geriatrics Units. METHODS: A cross-sectional study
      based on consecutive cutoff points in periods longer than the average stay in
      each unit, the patients admitted in the acute care units and average stay in the
      Geriatrics Unit of the Hospital Monte Narango (HMN) (n = 318), Hospital Central
      de la Cruz Roja (HCCR) (n = 384), Hospital General de Guadalajara (HG) (n = 272)
      and Hospital Virgen del Valle (HVV) (n = 390), with regard to the spread thereof
      according to the RUG-T18 classification. The possible differences among the
      hospitals in question were analyzed by means of the chi-square statistical test
      (SPSS for Windows). RESULTS: For the overall sample, the patients were divided
      into groups R, S and C of the classification, groups P and B being represented to
      a very small degree, differences having been found to exist among the different
      hospitals. Hence, the HCCR is that which handles the largest percentage of
      patients in the R group (47.64% vs. 23.66% at HMN; 20.57% at HG and 20.53% at
      HVV) and a smaller percentage of patients in the S Group (3.12% vs. 6.40% at HMN;
      9.92% at HG and 9.76% at HVV) and the C Group (48.94% vs. 76.29% at HMN; 66.89%
      at HG and 68.36% at HVV). Differences were likewise found to exist in the
      individual analysis for the acute care units and average length of stay.
      CONCLUSIONS: The resource usage groups can be useful with regard to ascertaining
      differences in the health care loads in hospital care for senior citizens.

PMID- 11515339
TI  - Confusion over levothyroxine settled.

PMID- 11515340
TI  - New Florida law restricts drugs for Medicaid.

PMID- 11515341
TI  - HHS clarifies privacy rule.

PMID- 11515342
TI  - CDC updates, combines occupational exposure guidelines for HBV, HCV, HIV.

PMID- 11515343
TI  - Utah uses controversial data for reporting errors.

PMID- 11515344
TI  - Americans make choices about self-care.

PMID- 11515345
TI  - R & D costs constitute small part of drug company expenses.

PMID- 11515346
TI  - Vision for pharmacy practice in hospitals and health systems.

PMID- 11515347
TI  - Harvey A. K. Whitney Lecture. Pharmacy and the complexity of health care.

PMID- 11515348
TI  - Comparative pharmacokinetics and pharmacodynamics of lansoprazole oral capsules
      and suspension in healthy subjects.
AB  - The pharmacokinetics and pharmacodynamics of lansoprazole suspension and
      lansoprazole capsules were studied. Thirty-six healthy males and females were
      randomized in a single-dose, open-label, two-period crossover study. Lansoprazole
      30 mg was administered via a nasogastric tube as simplified lansoprazole
      suspension (in 8.4% sodium bicarbonate) or orally as the intact capsule after a
      minimum 12-hour fast and 5 hours before lunch. Ambulatory 24-hour intragastric pH
      was monitored at baseline and on day 1 of each treatment period to assess
      lansoprazole's pharmacodynamics. Blood samples were collected before drug
      administration and at predetermined intervals up to 24 hours after each dose to
      assess lansoprazole's pharmacokinetics. Both formulations effectively raised the
      mean 24-hour intragastric pH (mean 24-hour pH of 3.75 with suspension and 3.52
      with intact capsule) and maintained it above threshold values of 3 and 4 for more
      than 40% of the 24-hour postdose period. The suspension was associated with a
      significantly shorter mean time to the maximum observed concentration (tmax)
      compared with the intact capsule. The mean maximum observed plasma concentration
      (Cmax) of the suspension was significantly higher and the mean area under the
      concentration-time curve from time zero to infinity (AUC infinity) was
      significantly lower than those of the intact capsule (879 versus 810 ng/mL and
      1825 versus 2229 ng.hr/mL). The 90% confidence intervals obtained by two one
      sided tests for both Cmax and AUC infinity were contained within the 0.80 to 1.25
      range, confirming the bioequivalence of the two regimens. Simplified lansoprazole
      suspension effectively controls intragastric pH, is bioequivalent to the intact
      capsule, and represents an effective therapeutic option for patients who have
      difficulty swallowing or are unable to swallow lansoprazole capsules.

PMID- 11515349
TI  - Implementing a personal digital assistant to document clinical interventions by
      pharmacy residents.

PMID- 11515350
TI  - Turning the tide: bringing about positive change in pharmacy.

PMID- 11515351
TI  - Out in front: ASHP advances practice through leadership.

PMID- 11515352
TI  - 2001 report of the treasurer. Looking back, moving ahead.

PMID- 11515353
TI  - Mastering change: strengthening ASHP to meet the needs of a new century.

PMID- 11515354
TI  - Rapid DNA fiber technique for size measurements of linear and circular DNA
      probes.

PMID- 11515355
TI  - Method to introduce stable, expanded, polyglutamine-encoding CAG/CAA
      trinucleotide repeats into CAG repeat-containing genes.

PMID- 11515356
TI  - Vectors for high-level expression of cDNAs controlled by tissue-specific
      promoters in transgenic mice.

PMID- 11515357
TI  - AdEasy system made easier by selecting the viral backbone plasmid preceding
      homologous recombination.

PMID- 11515358
TI  - PCR-based method for the construction of gene disruption cassettes in yeast.

PMID- 11515360
TI  - Isolation and subcloning of large fragments from BACs and PACs.

PMID- 11515359
TI  - High-probability amplification of genomic DNA starting from cDNA.

PMID- 11515361
TI  - Enhanced detection of multiplex PCR products using SYBR Green I and an automated
      DNA sequencer.

PMID- 11515362
TI  - Identification of trisomy 16 murine embryos by fluorescence in situ
      hybridization.

PMID- 11515363
TI  - De-chorionation of fixed zebrafish embryos.

PMID- 11515364
TI  - Extraction of microbial DNA from rumen contents containing plant tannins.

PMID- 11515365
TI  - Cryo field emission scanning electron microscopy.

PMID- 11515366
TI  - Vector for pop-in/pop-out gene replacement in Pichia pastoris.
AB  - Gene replacement in yeast is often accomplished by using a counterselectable
      marker such as URA3. Although ura3 strains of Pichia pastoris have been
      generated, these strains are inconvenient to work with because they grow slowly,
      even in the presence of uracil. To overcome this limitation, we have developed an
      alternative counterselectable marker that can be used in any P. pastoris strain.
      This marker is the T-urf13 gene from the mitochondrial genome of male-sterile
      maize. Previous work showed that expression of a mitochondrially targeted form of
      T-urf13 in Saccharomyces cerevisiae rendered the cells sensitive to the
      insecticide methomyl, and similar results have now been obtained with P.
      pastoris. We have incorporated T-urf13 into a vector that also contains an ARG4
      marker for positive selection. The resulting plasmid allows for pop-in/pop-out
      gene replacement in P. pastoris.

PMID- 11515368
TI  - Novel vectors for co-expression of two proteins in E. coli.
AB  - Two new vectors, pAC28 and pEGST, for the co-expression of recombinant genes in
      E. coli were developed. This two-plasmid system allows for an efficient
      expression and purification of large amounts of protein-protein complexes formed
      in bacterial cells. We have utilized this new system to express and isolate a
      stable complex of two human proteins, hematopoietic cell tyrosine phosphatase
      (HePTP) and mitogen-activated proteins kinase Erk2. This approach is useful for
      biochemical and structural studies of protein-protein interactions.

PMID- 11515367
TI  - Fluorescence produced by transfection reagents can be confused with green
      fluorescent proteins in mammalian cells.
AB  - The Aequorea victoria green fluorescent protein (GFP) reporter system is a
      convenient way to monitor gene expression and other cellular functions in
      mammalian cells. To study gene expression, a GFP-fusion plasmid construct is
      often transfected into mammalian cells using a variety of methods including
      calcium phosphate- and liposome-based DNA transfer. Subsequently, the expression
      of GFP-fusion protein is monitored by fluorescence microscopy or flow cytometry.
      Here, we report that certain transfection reagents can produce fluorescence that
      can be detected in a wide range of wavelengths, which can be confused with GFP
      fusion protein. The fluorescence false positives can be a problem, particularly
      when the GFP expression levels are low. To improve the GFP-based detection or
      screening methods, it is imperative to include an appropriate negative control
      and to detect GFP using a narrow-wavelength emission filter corresponding to the
      emission spectrum around the GFP peak.

PMID- 11515369
TI  - Elimination of transcriptional interference between tandem genes in plant cells.
AB  - Plant cells are commonly transformed with two or more tandemly arranged genes,
      but how orientation affects their expression is not well understood. We
      investigated the amount of transcriptional interference occurring between two
      adjacent genes by cloning luciferase and green fluorescent protein (GFP) genes
      (promoter--coding sequence--terminator) in all possible orientations and
      expressing the genes in tobacco protoplasts. When two genes are oriented head-to
      tail (-->-->), the expression of the downstream gene was reduced 80% by the
      upstream gene. When two genes are oriented tail-to-tail (--><--), the expression
      of the upstream gene was reduced 53% by the expression of the downstream gene.
      There was no interference when the orientation was head-to-head (<---->). Using a
      chemically inducible gene expression system, we showed that the downstream gene
      expression was reduced 71% by the induction of an upstream gene. Inserting a
      mammalian transcription blocker sequence eliminated the interference between the
      genes in tail-to-tail orientation. The interference in the head-to-tail
      orientation was eliminated by inserting a 2322-bp lambda phage DNA fragment. The
      terminators in gene constructs did not prevent the transcriptional interference,
      and the interference was eliminated by designing the orientation of genes and by
      placing a transcription blocker or a lambda phage sequence between genes.

PMID- 11515370
TI  - Bifunctional protein conferring enhanced green fluorescence and puromycin
      resistance.
AB  - A new genetic marker was created in which sequences from enhanced green
      fluorescent protein were fused to those of puromycin N-acetyl transferase. The
      resulting fusion protein (EGFP-puro) conferred both green fluorescence and
      resistance to puromycin when expressed in mammalian cells. The utility of EGFP
      puro as a selectable/screenable marker was demonstrated by the ease with which a
      recombinant guinea pig cytomegalovirus containing EGFP-puro was isolated by a
      combination of puromycin selection and screening for green fluorescence. We
      conclude that EGFP-puro is a compact and versatile marker that should prove
      useful for recombinant virus and transgenic cell line construction, particularly
      in applications in which coding capacity is limited.

PMID- 11515371
TI  - Generating tandem repeats by cloning with double initiator fragments.
AB  - The ability to generate tandem repeats of a DNA sequence has proven important for
      a large variety of studies of DNA structure and function. The most commonly used
      method to produce tandem repeats involves cloning of an oligomerized monomer
      sequence that contains asymmetric overlapping ends, but, in practice, this
      approach is inefficient because of the circularization of oligomers before they
      ligate into vector. Described here is a method that circumvents this problem by
      the use of two separate oligomerization reactions, each containing an initiator
      fragment onto which monomer polymerizes without circularization. Subsequent
      mixing of the two reactions permits circularization, generating a viable plasmid
      containing the sum of the added repeats from each reaction. A variation of this
      method is also demonstrated that permits the synthesis of constructs with a
      defined number of repeats.

PMID- 11515372
TI  - Generation of high-quantity and quality tag/ditag cDNAs for SAGE analysis.
AB  - The serial analysis of gene expression (SAGE) technique is an important tool for
      genome-wide gene expression analysis. However, the requirement of a large amount
      of mRNA for the analysis and the difficulties in generating high-quality tag and
      ditag fragments for the construction of a SAGE library often interfere with the
      successful performance of the SAGE technique. We developed two procedures to
      solve these issues: (i) introducing low-cycle PCR amplification of the 3' cDNA
      before the BsmFI digestion of the 3' cDNAs and (ii) gel purifying the BsmFI
      released tag fragments before ditag formation. These modifications provide a
      large quantity of initial 3' cDNAs and high-quality tags and ditags for the
      construction of SAGE libraries.

PMID- 11515373
TI  - Development of simple sequence repeat markers from bacterial artificial
      chromosomes without subcloning.
AB  - Simple sequence repeats (SSRs) were isolated from pearl millet bacterial
      artificial clones (BACs) without any subcloning steps. SSR sequences were
      targeted using 3' end-anchored SSR primers. Flanking sequences were isolated by
      suppression PCR. In this pilot study, 25 SSR markers have been developed from 40
      BAC pools, comprising a total of 384 clones. This novel way to develop new
      markers has the added advantage that mapping the SSR markers will anchor
      individual BACs to the genetic maps and, thus, facilitate the construction of BAC
      contigs.

PMID- 11515374
TI  - DNA polymerases as engines for biotechnology.
AB  - This review examines the DNA polymerases, a class of enzymes that has been an
      essential tool for molecular biology research. Several families of DNA
      polymerases have been defined based on amino acid sequence comparisons, and new
      enzymes are continually being discovered, driving the expansion of the current
      classifications. Structural similarities among the enzymes are examined, as well
      as the functions of the various subunits and enzyme domains. The natural variety
      of polymerase activities has been harnessed for applications such as
      amplification, labeling, and detection of DNA sequences. In addition,
      enhancements to DNA polymerases by genetic engineering will be described, such as
      enzymes specifically designed for DNA sequencing by improving the incorporation
      of dideoxynucleotide terminators. Reverse transcription, the ability to use RNA
      as a template for DNA synthesis, is described for the application of making cDNA.
      We believe that new and unanticipated applications will emerge as new polymerases
      and mutated polymerases are created and characterized.

PMID- 11515375
TI  - New directions in carbohydrate engineering: a metabolic substrate-based approach
      to modify the cell surface display of sialic acids.
AB  - This review discusses new directions in the emerging field of carbohydrate
      engineering. Specifically, it describes substrate-based methodologies that are
      complementary to the recombinant DNA techniques that now dominate metabolic and
      cellular engineering endeavors. A substrate-based approach consists of
      intercepting a biosynthetic pathway with an unnatural analog of a metabolic
      intermediate. The unnatural compound competes with the endogenous substrate for
      biosynthetic incorporation into a cellular component by action of the natural
      enzymes of the cell. The incorporation of the unnatural compound into the
      cellular architecture can directly modulate cellular properties and biological
      processes. Alternatively, a molecular handle can be included in the design of the
      unnatural substrate that allows further elaboration upon reaction with an
      externally delivered reagent. The sialic acid biosynthetic pathway is presented
      as a model system to illustrate both the practical aspects and theoretical
      considerations of a substrate-based cellular engineering approach. Specific
      applications of carbohydrate-based cell surface engineering include chemical
      construction of new glycosylation patterns on cells, new approaches to targeting
      tumor cell with either diagnostic or therapeutic agents, and installation of
      novel receptors on cells for facilitating viral-mediated gene delivery.

PMID- 11515376
TI  - Integrating retroviral cassette extends gene delivery of HSV-1 expression vectors
      to dividing cells.
AB  - Retroviral vectors have long been used in a wide variety of gene transfer
      applications but have certain drawbacks, such as small cargo size, limited
      tropism, and low titers. HSV expression vectors overcome these disadvantages,
      but, because they persist in target cells as nonreplicative episomes, they are
      not retained in all the progeny of dividing cells. Chimeric HSV/AAV products that
      can mediate transgene integration in human mitotic cells have been constructed,
      but, to date, genetic modification of dividing cells in animal models using HSV
      products has not been possible. Here, we report the construction of hybrid
      HSV/retroviral vectors that exhibit up to 50-fold higher transgene integration
      efficiency compared to vectors containing only HSV-1 components. Efficient
      integration of a retroviral transgene cassette encoding pac in human cells
      required expression of the Moloney murine leukemia virus gag-pol genes, but in
      murine cells, could also be mediated by endogenous activities, albeit at a lower
      level. Gene delivery was equally efficient in BHK21, a cell line resistant to
      retroviral infection, and transgene retention and expression were observed to be
      stable for least one month in Hs683 human glioma cells. These vectors have wide
      applications for the genetic modification of many cell types.

PMID- 11515377
TI  - Application of fluorescently labeled poly(dU) for gene expression profiling on
      cDNA microarrays.
AB  - The membrane filter hybridization technique has been widely used for gene
      expression profiling. The preparation of sensitive and reliable probes is
      critical for quantitative analysis in this technique. We report a method in which
      fluorescently labeled poly(dU) is used to detect poly(A)-containing mRNA that
      hybridizes to specific gene targets. The probe can be used commonly for every
      sample, alleviating problems encountered in preparing cDNA probes by reverse
      transcription, particularly when many samples are to be analyzed. Moreover, the
      sensitivity is at least comparable to cDNA probes prepared by conventional
      protocols, and intensities of signals after hybridization are independent of mRNA
      sizes and solely dependent on copy numbers. This method was also shown to be
      applicable to DNA chip technology.

PMID- 11515378
TI  - Method for screening ecdysone-inducible stable cell lines.
AB  - Ecdysone-inducible systems are useful tools to study the function of various
      genes in different types of mammalian cells. However, it is technically difficult
      to establish stable cell lines. This is partly because the conditional expression
      system requires the expression of two or more components driven by different
      kinds of promoters. In this paper, we describe the use of a luciferase reporter
      gene system for rapid screening of cell lines that express the ecdysone and
      retinoid X receptors. Using this system, two human stable colon cancer cell
      lines, SW480/VgRXR and HCT116/VgRXR, were successfully generated. The expression
      of these receptors remained high after six months of continuous culturing. A
      tight regulation of gene induction in SW480/VgRXR was observed using 2 microM
      Ponasterone A. The gene induction was rapid and persistent. Our results
      demonstrated the advantage of establishing cell lines that continuously express
      high levels of ecdysone receptor proteins.

PMID- 11515379
TI  - Bioluminometric method for real-time detection of ATPase activity.
AB  - We have developed a real-time, simple, and sensitive method for the detection of
      ATP hydrolysis activity (ATPase) of apyrase (EC 3.6.1.5). The assay is based on
      the continuous monitoring of the ATP hydrolysis reaction using the firefly
      luciferase system. The method is sensitive and yields linear responses between
      0.7 and 70 mU for the Solanum tuberosum apyrase. The detection limit was found to
      be 0.7 mU apyrase. We used the method to study the inhibitory effects of various
      compounds on the ATPase activity of potato apyrase, measured with 500 nM ATP. The
      concentrations of azide, AMP, Pi, fluoride, and ADP, which inhibit the ATPase
      activity by 50% (IC50), were found to be approximately 100, 0.25, 0.125, 0.04,
      and 0.035 mM, respectively. Under our assay conditions, vanadate inhibited about
      98% of the ATPase activity of the potato apyrase at a concentration of 250
      microM. The possibility of using the new method for other applications is
      discussed.

PMID- 11515380
TI  - PCR-based detection of genetically modified soybean and maize in raw and highly
      processed foodstuffs.
AB  - The PCR method has proved to be an invaluable tool for the specific and sensitive
      detection of genetically modified material (e.g., Roundup Ready Soybean and Bt
      176 "Maximizer" Maize) in foodstuffs. The first step in the procedure, namely the
      purification of nucleic acids from the sample, is often the deciding factor in
      the production of meaningful results. In this study, we present two procedures
      that enable an efficient isolation of trace amounts of genetic material from both
      raw and highly processed foodstuffs. We show that for optimal, PCR-ready DNA
      purification from highly processed foodstuffs and PCR inhibitor-rich substances-
      such as cocoa-containing products--adapted protocols for the QIAGEN QIAamp DNA
      Stool Mini Kit can be utilized. For complete DNA isolation from raw foodstuffs, a
      protocol using the DNeasy Plant Mini Kit is presented.

PMID- 11515381
TI  - An Oklahoma perspective: end-of-life decision-making and termination of
      treatment.

PMID- 11515382
TI  - Effectiveness of a Mobile Outreach and Crisis Services unit in reducing
      psychiatric symptoms in a population of homeless persons with severe mental
      illness.
AB  - The purpose of this study was to use a time-lag design to evaluate the
      effectiveness of a Mobile Outreach and Crisis Services unit in remitting
      psychiatric symptomatology, improving global functioning, and decreasing
      homelessness in a population of homeless, severely mentally ill residing in a mid
      sized urban center. Using a time-lag study design, two groups of subjects--25
      individuals before receiving services (control group) and 25 individuals after
      receiving services (experimental group)--were contrasted across outcome measures.
      The results indicate that a MOCS unit utilizing a Program for Assertive Community
      Treatment mode was effective in significantly decreasing psychiatric
      symptomatology, reducing homelessness, and increasing global functioning. If
      carefully implemented and interpreted, a time-lag design may be a means of
      providing valuable feedback and information in a timely manner.

PMID- 11515383
TI  - Medications for the treatment of Alzheimer's disease.
AB  - At the time this article was written, there were only three medications approved
      by the Federal Drug Administration for the treatment of Alzheimer's Disease.
      Currently there are four approved medications. The newest drug, galantamine, is
      not reviewed in this article.

PMID- 11515384
TI  - Update on nursing home care in Oklahoma.
AB  - In Oklahoma approximately 36,000 people live in a nursing home. This article
      reviews those initiatives by Medicare, the Health Care Finance Administration
      (HCFA), and the American Medical Directors' Association to improve the quality of
      care that physicians and nurses provide to residents in long-term care
      facilities, specifically nursing homes.

PMID- 11515385
TI  - Prevention and early detection of type 2 diabetes in children and adolescents.
AB  - Type 2 ("adult-onset") diabetes in young adults and children has become
      increasingly common over the last 10 years, and has been described as an
      "emerging epidemic." The financial and societal ramifications of such a
      development are substantial and demand a prompt and aggressive public health
      response. Emphasis must be placed upon preventive behaviors and early detection,
      and creation of new public policy to address the related societal issues.
      Recommendations for prevention and screening of high-risk children and
      adolescents are provided.

PMID- 11515386
TI  - The Iowa Medical Society's 2002 physician advocacy agenda--a preview.

PMID- 11515387
TI  - Legislature expands AIDS testing laws to address law enforcement concerns.

PMID- 11515388
TI  - Why go to medical school when you can go to the Iowa Legislature?

PMID- 11515389
TI  - Every subpoena requires a response.

PMID- 11515390
TI  - HIPPA will change your business relationships.

PMID- 11515391
TI  - 'Caveat emptor' is a tempting approach, but wrong for patients.

PMID- 11515392
TI  - [Significance of sibling relations in parental separation].
AB  - Sibling relationships ar a new field in empirical science, and existing data are
      rather sparse. An overview will be given about the diversity of sibling
      relationships. General research results will be reported briefly, and special
      emphasis will be put on the situation of siblings in families undergoing divorce.
      Starting with the situation of current research an their diverse results two
      major studies will be described more closely (Conger and Conger 1996; Schmidt
      Denter and Beelmann 1995). Furthermore problems of research in the area of
      sibling relationships will be discussed. Implications of these research results
      for expert opinions in custody cases will be presented (Karle et al. 2000). A
      following case study will again demonstrate the complexity of this topic.

PMID- 11515393
TI  - [Sibling relations between individuation and attachment: attempt at a
      conceptualization].
AB  - Although sibling relationships can be considered as one of the most durable and
      intensive relationships, not much research in developmental psychology and family
      research has been done on this issue. The strong focus on parents, more
      specifically on mothers, stood in the way of adequate conceptualization and
      understanding of the function and contribution of siblings to individual
      development and family interaction. In this contribution a conceptualization of
      sibling relationships is presented. Siblings as objects of aggressive and sexual
      feelings as well as the function of siblings in the family system, for example,
      as parentification and negative identity is emphasized. In addition, the
      different qualities of sibling relationships, for example, envy, rivalry,
      similarity, and difference, are emphasized. The function of siblings as love
      objects is stressed, and the role of siblings as support as well as teaching
      object is illustrated. Finally, it is emphasized that, similar to relationships
      between parents and child, the quality of sibling relationships changed over time
      and leads, for example, to a detachment between sibling relationships during
      adolescence.

PMID- 11515394
TI  - [Sibling relations from the family therapy perspective--support, attachment,
      rivalry and envy].
AB  - In family therapy, during the last years more and more importance is attached to
      the dynamics of the sibling subsystem. In the present paper differences between
      them as well as similarities are discussed from the point of view of family
      theory. Relevant dimensions like support, attachment, rivalry and envy between
      brothers and sisters contribute essentially to the family dynamics. In this
      clinically orientated paper, we describe by means of a case example how the
      couple's conflicts after their separation is unconsciously repeated in the
      sibling subsystem. It is shown how the intergenerational dynamics can be
      interrupted by the initiative of the children and the initiated family therapy.

PMID- 11515395
TI  - [Sibling relations in processing sexual trauma: the film "The Celebration"]].
AB  - Movies appeal as a subject of psychoanalytical art interpretation due to their
      structural closeness to "scenical understanding" and enrich our Insight into
      human relationships. The movie Das Pest is worth seeing because of its particular
      aesthetic form and because of its message about sibling relationships. According
      to the assessment of film journalists the movie shows the dismantling of middle
      class society and the reinscenation of destructive violence. In this author's
      interpretation, however, the movie leads out of passing violence on through the
      generations and herein differs from numerous current movies about siblings. The
      movie is about the process of a constructive development in the reciprocal
      relationships between four siblings and shows this in the formal structure of a
      film. With countertransference and our "viewing habits" the author discusses why
      this development could be overlooked. The movie shows neither a sibling fixation
      nor an idealization of sibling love as a regressive, timeless topos, but rather a
      horizontal relationship process. This is open towards partners and allows for a
      conciliatory attitude towards the parents. The movie is able to show this process
      conclusively under the burden of intergenerational violence and in its creativity
      enriches our image of sibling relationships.

PMID- 11515396
TI  - Variation in hominid brain size: how much is due to method?
AB  - Brain size represented by cranial capacity (CC) is one of the most frequently
      analysed characters of hominids. Accuracy of individual CC estimates depends on
      completeness of specimens and methods used for reconstruction and measurement. A
      file of published estimates of CC of hominids dated from 3.2 Ma (million years)
      to 10 Ka (thousand years) including 606 estimates for 243 specimens was compiled.
      In the file, 75 specimens are available with multiple values (3 to 15) obtained
      by various methods and/or by various authors. Using individuals as classes in
      ANOVA, intraclass variation, which represents "error" of estimates, was
      calculated. For the total sample of multiple estimates (N = 382) the error
      variance is 5315 ml2. The error standard deviation is 73 ml (coefficient of
      variation (CV = 7.3%), quite large in comparison to the actual variation in CC in
      modern humans, SD = 157 ml (CV = 11.6%). This large error makes us wonder whether
      any fossil can be reliably placed with respect to a particular "cerebral Rubicon"
      between palaeospecies. Recent discussions concerning cranial capacity of Stw505
      are a case in point regarding errors in CC estimation. In actual repeated 30 time
      measurements on a research quality cast we obtained with various methods (water,
      seeds, plasticine) CC estimates ranging from 484 to 586 ml. The range of
      estimates in the literature is from 515 to 625 ml. When hominid CC by taxon with
      date as a covariate is subjected to ANOVA, taxon is responsible for 5% of the
      variance while date is responsible for the main portion, (89%). The relationship
      between CC and date is best characterised as a gradual time trend. It is proven
      by the ANOVA test for linearity, by gamma test for trend and by ASReml fitting of
      a linear function. The line of best fit to this time trend is a double
      exponential curve which explains 90% of the total variance in CC: CC = 306.63
      (4.83(0.9995)DATE) Essentially the same curve fits subsamples of CC dated at less
      than 1 Ma and at 3.2-1.0 Ma. This has several implications for the nature of the
      Darwinian process to be reconstructed.

PMID- 11515397
TI  - Incremental lines of dental cementum in biological age estimation.
AB  - The aim of this study is to evaluate the use of counting incremental lines of
      dental root cementum for biological age determination, and to compare it with
      alternative methods. Two samples were taken: 51 teeth from 49 individuals of
      known age obtained at the Stomatological Clinic, Vilnius University, as well as
      the canine teeth from the remains of 48 individuals from the mass graves of
      Tuskulenai in Vilnius (inhumed 1944-47). In the latter sample, the chronological
      age of 43 individuals was known through personal identification. Undecalcified
      teeth were sectioned with the Leica SP 1600 microtome diamond saw, and
      incremental line count as a blind test was made on sections of 35 to 100 microns
      thickness. Incremental line count was possible in 82-86 percent of cases. The
      results of three independent counts showed that intra-observer bias has no
      significant impact. Biological age was estimated by adding incremental line
      number to the average age of tooth eruption. It was found that mean absolute
      error was 6.46 years for the 1st sample, 6.27 years for the 2nd sample, and in
      some cases exceeded 10 years. For the 2nd sample, the results were compared to
      those of other methods such as endocranial suture ossification, pubic symphysis
      morphology and the "combined" method of Nemeskeri. All four methods yield a
      similar correlation in regard to an individual's chronological age. The highest
      correlation was found for the combined method, and the lowest one for public
      symphysis morphology. All correlations had a similar standard error. Thus our
      assessment is less enthusiastic than in some past studies; it is suggested that
      the incremental lines rather have a similar use as other methods.

PMID- 11515398
TI  - Nicotine use in early mediaeval Kirchheim/Teck, Germany.
AB  - Human bone samples of 123 Alemans of the 5th to 7th c AD were investigated for
      nicotine. In 23 individuals nicotine was found at levels between 31 and 150 ng/g,
      and in 49 others nicotine was found in traces. The results indicate that in
      Germany plants of the genus Nicotiana should have been present, known and used,
      well before Columbus. The purposes behind this use might have been
      domestic/medical or ritual, or possibly even as a luxury as occurs today.

PMID- 11515400
TI  - Ectoparasite control in small ruminants.
AB  - Ectoparasites are a common problem in small ruminants of North America.
      Management of ectoparasites in small ruminants can be challenging for producers
      and veterinarians. It is important for the veterinarian to make an accurate
      diagnosis of the type of ectoparasite that is infesting the animal, then to
      develop a plan that most effectively and economically controls the ectoparasite.
      Effective and economic control of an ectoparasite infestation begins with an
      understanding of the ectoparasite's life cycle and how that life cycle affects
      the animal. It should be noted that climate and geographical area can affect the
      life cycle of specific ectoparasites, so it is important for veterinarians to
      educate themselves about their specific environment. Once the life cycle has been
      addressed, then the veterinarian should decide which intervention will provide
      the best control. Intervention possibilities may range from insecticides to
      environmental management or a combination of several methods. The veterinarian
      should provide the producer with realistic goals that define specific limitations
      of ectoparasite control.

PMID- 11515399
TI  - Internal parasite control strategies.
AB  - To maintain the general health of small ruminants, owners, managers, and
      clinicians should be familiar with the body condition-scoring [table: see text]
      methods, general health, and overall appearance of the animals in their care. Any
      changes in the overall health of individual animals or the flock should be noted
      immediately, the cause determined, and immediate measures should be taken to
      correct any problems. Parasite management in small ruminants is a difficult and
      arduous task. When a program that reduces parasite infestation is discovered, it
      should be carefully implemented, maintained with vigilance, and constantly
      "tweaked" to maximize its effectiveness.

PMID- 11515401
TI  - Interpreting physical evidence of predation on hoofstock and management
      alternatives for coping with predators.
AB  - Predation on domestic and wild hoofstock is a serious management constraint,
      especially for small ruminants and neonates. Diagnosis of the species of predator
      responsible for livestock losses relies on the ability to interpret direct and
      indirect evidence of predation. This article summarizes the physical evidence
      associated with depredation events and includes the most common species of
      predators encountered in North America. Management alternatives for coping with
      predators are discussed.

PMID- 11515402
TI  - Ovine scrapie. New tools for control of an old disease.
AB  - Ovine scrapie was described nearly 300 years ago and is endemic in many parts of
      the world. The recent emergence of a related bovine disease in the United Kingdom
      and Europe, with probable transmission to humans, has lent urgency to scrapie
      surveillance and control programs. The biology, genetics, diagnosis, and proposed
      routes of transmission can be understood in the context of the presumed causative
      agent, the prion protein. An integrated program of management and husbandry to
      reduce introduction and spread of the disease within a flock, diagnosis of
      preclinically infected sheep in both live animal and postmortem settings, and
      identification of breeding stock of low risk of scrapie are reviewed as the basis
      for scrapie eradication programs.

PMID- 11515403
TI  - Chlamydial infections in small ruminants.
AB  - Chlamydophila abortus (formerly Chlamydia psittaci) is one of the most important
      causes of reproductive failure in sheep and goats, especially in intensively
      managed flocks. The disease is usually manifested as abortion in the last 2 to 3
      weeks of gestation, regardless of when the animal was infected. Ewes that abort
      are resistant to future reproductive failure due to C. abortus, but they become
      inapparent carriers and persistently shed the organism from their reproductive
      tracts during estrus. Chlamydophila pecorum is the other member of the genus that
      affects small ruminants, and it is recognized as a primary cause of
      keratoconjunctivitis in sheep and goats and of polyarthritis in sheep.

PMID- 11515404
TI  - Mycoplasma infections in small ruminants.
AB  - Mycoplasmas have complex mechanisms of antigenic variation that allow them to
      evade the immune system. These organisms cause a variety of clinical syndromes
      that can have a significant economic effect on small ruminant production. The
      syndromes range from acute septicemia and death to chronic infection resulting in
      decreased production. Recent research findings have shed light on the means by
      which these organisms evade the host immune response and cause or contribute to
      the development of disease in the host. This article provides a review of the
      pathogenesis, clinical signs, and treatment options for common disease syndromes
      involving Mycoplasma spp. in small ruminants.

PMID- 11515405
TI  - Mastitis of sheep and goats.
AB  - This article presents an overview of the recent research into ovine and caprine
      mastitis. The common clinical presentations of mastitis in these species are
      reviewed, as are the important etiologic agents and their significance. The
      interpretation of somatic cell counts and surrogate tests, factors that affect
      somatic cell count levels, and association of somatic cell count levels with
      productivity are reviewed. Investigations into the treatment and prevention of
      mastitis and milking equipment function are discussed, and comments are made on
      the public health implications of extra label drug use and the consumption of
      unpasteurized milk.

PMID- 11515406
TI  - Caseous lymphadenitis in small ruminants.
AB  - Caseous lymphadenitis is a contagious bacterial disease that affects sheep and
      goats. It is characterized by abscess formation in the skin, internal and
      external lymph nodes, and internal organs. The causative agent is Corynebacterium
      pseudotuberculosis. The disease can become endemic in a herd or flock and is
      difficult to eradicate by virtue of its poor response to therapeutics, its
      ability to persist in the environment, and the limitations in detecting
      subclinically affected animals. The disease causes significant economic impact on
      the small ruminant industry through decreased meat yield, damaged wool and
      leather, decreased reproductive efficiency, culling of affected animals, and
      mortality from the internal environment.

PMID- 11515407
TI  - Selenium and vitamin E.
AB  - Deficiency of selenium and vitamin E has recently been identified as a major
      health concern of sheep producers in certain regions of the United States, and
      familiarity with published data on these nutrients seems to be of value to small
      ruminant practitioners. This article begins with a description of the biochemical
      roles and metabolism of selenium and vitamin E. A literature review follows in
      which the influence of these nutrients on the musculoskeletal, reproductive, and
      immune systems, as well as on flock productivity, is discussed. Methods for
      detection of deficiency and supplementation strategies are also described.

PMID- 11515408
TI  - Label and extra label drug use in small ruminants.
AB  - The small ruminant practitioner has a small arsenal of approved drugs in the
      United States, so the practitioner must be familiar with the laws and regulations
      related to extra label use. Drugs can be used extra label in food animals only
      under specific circumstances and can be used only for therapeutic purposes. Drugs
      that are illegal in small ruminants include chloramphenicol; clenbuterol;
      diethylstilbestrol; dimetridazole, ipranidazole, and other nitroimidazoles such
      as metronidazole; dipyrone; fluoroquinolones; glycopeptides; nitrofurans;
      furazolidone; and extra label use of medication in feed. It is also illegal to
      use any drug that results in residues above established tolerances or safe
      levels.

PMID- 11515409
TI  - Advanced reproductive techniques in goats.
AB  - The use of ultrasonography for pregnancy diagnosis and reproductive tract
      evaluation in the goat has become more common in the past decade. Pregnancy
      specific hormone assays are commercially available for pregnancy determination in
      goats. Hormonal methods of synchronization of estrus for artificial insemination
      have been refined, but a number of factors still make pregnancy results variable.
      Caprine embryo transfer is widely used commercially. More advanced reproductive
      techniques such as in-vitro production of embryos and cloning have been
      accomplished in goats; success rates with these techniques will likely rapidly
      improve.

PMID- 11515410
TI  - Reproductive techniques in sheep.
AB  - This article reviews current methods of evaluating reproductive performance in
      the sheep industry. The reproductive technologies of breeding soundness
      examination, reproductive ultrasonography, estrus manipulation, artificial
      insemination, and embryo transfer are also extensively discussed. The
      veterinarian's current and future role in the application of these technologies
      is discussed.

PMID- 11515412
TI  - Wavelets and imaging informatics: a review of the literature.
AB  - Modern medicine is a field that has been revolutionized by the emergence of
      computer and imaging technology. It is increasingly difficult, however, to manage
      the ever-growing enormous amount of medical imaging information available in
      digital formats. Numerous techniques have been developed to make the imaging
      information more easily accessible and to perform analysis automatically. Among
      these techniques, wavelet transforms have proven prominently useful not only for
      biomedical imaging but also for signal and image processing in general. Wavelet
      transforms decompose a signal into frequency bands, the width of which are
      determined by a dyadic scheme. This particular way of dividing frequency bands
      matches the statistical properties of most images very well. During the past
      decade, there has been active research in applying wavelets to various aspects of
      imaging informatics, including compression, enhancements, analysis,
      classification, and retrieval. This review represents a survey of the most
      significant practical and theoretical advances in the field of wavelet-based
      imaging informatics.

PMID- 11515411
TI  - A knowledge-based, concept-oriented view generation system for clinical data.
AB  - Information overload is a well-known problem for clinicians who must review large
      amounts of data in patient records. Concept-oriented views, which organize
      patient data around clinical concepts such as diagnostic strategies and
      therapeutic goals, may offer a solution to the problem of information overload.
      However, although concept-oriented views are desirable, they are difficult to
      create and maintain. We have developed a general-purpose, knowledge-based
      approach to the generation of concept-oriented views and have developed a system
      to test our approach. The system creates concept-oriented views through automated
      identification of relevant patient data. The knowledge in the system is
      represented by both a semantic network and rules. The key relevant data
      identification function is accomplished by a rule-based traversal of the semantic
      network. This paper focuses on the design and implementation of the system; an
      evaluation of the system is reported separately.

PMID- 11515413
TI  - Cell image segmentation with kernel-based dynamic clustering and an ellipsoidal
      cell shape model.
AB  - In this paper, we propose a novel approach to cell image segmentation under
      severe noise conditions by combining kernel-based dynamic clustering and a
      genetic algorithm. Our method incorporates a priori knowledge about cell shape.
      That is, an elliptical cell contour model is introduced to describe the boundary
      of the cell. Our method consists of the following components: (1) obtain the
      gradient image; (2) use the gradient image to obtain points which possibly belong
      to cell boundaries; (3) adjust the parameters of the elliptical cell boundary
      model to match the cell contour using a genetic algorithm. The method is tested
      on images of noisy human thyroid and small intestine cells.

PMID- 11515414
TI  - Automatic lumbar vertebral identification using surface-based registration.
AB  - This work proposes the use of surface-based registration to automatically select
      a particular vertebra of interest during surgery. Manual selection of the correct
      vertebra can be a challenging task, especially for closed-back, minimally
      invasive procedures. Our method uses shape variations that exist among lumbar
      vertebrae to automatically determine the portion of the spinal column surface
      that correctly matches a set of physical vertebral points. In our experiments, we
      register vertebral points representing posterior elements of a single vertebra in
      physical space to spinal column surfaces extracted from computed tomography
      images of multiple vertebrae. After registering the set of physical points to
      each vertebral surface that is a potential match, we then compute the standard
      deviation of the surface error for each registration trial. The registration that
      corresponds to the lowest standard deviation designates the correct match. We
      have performed our current experiments on two plastic spine phantoms and two
      patients.

PMID- 11515415
TI  - Accessing heterogeneous sources of evidence to answer clinical questions.
AB  - The large and rapidly growing number of information sources relevant to health
      care, and the increasing amounts of new evidence produced by researchers, are
      improving the access of professionals and students to valuable information.
      However, seeking and filtering useful, valid information can be still very
      difficult. An online information system that conducts searches based on
      individual patient data can have a beneficial influence on the particular
      patient's outcome and educate the healthcare worker. In this paper, we describe
      the underlying model for a system that aims to facilitate the search for evidence
      based on clinicians' needs. This paper reviews studies of information needs of
      clinicians, describes principles of information retrieval, and examines the role
      that standardized terminologies can play in the integration between a clinical
      system and literature resources, as well as in the information retrieval process.
      The paper also describes a model for a digital library system that supports the
      integration of clinical systems with online information sources, making use of
      information available in the electronic medical record to enhance searches and
      information retrieval. The model builds on several different, previously
      developed techniques to identify information themes that are relevant to specific
      clinical data. Using a framework of evidence-based practice, the system generates
      well-structured questions with the intent of enhancing information retrieval. We
      believe that by helping clinicians to pose well-structured clinical queries and
      including in them relevant information from individual patients' medical records,
      we can enhance information retrieval and thus can improve patient-care.

PMID- 11515416
TI  - Maintaining and incrementally revalidating a computer-based clinical guideline: a
      case study.
AB  - The paper explores the issues involved in maintaining the logic within a complex
      computer-based clinical guideline, using as a case study IMM/Serve, an
      operational guideline whose domain is childhood immunization. For a period of
      more than a year and a half, we have maintained a log of (1) the national changes
      to the immunization recommendations, (2) the local customizations of IMM/Serve's
      logic, and (3) certain logic problems that arose in the process of accommodating
      these changes and customizations. We describe the nature of these changes,
      customizations, and problems. We also discuss how different types of domain
      knowledge might assist in the automated process of validating successive versions
      of the logic. The paper's goal is to use the immunization domain to provide
      specific examples of the issues and problems that arise in maintaining a computer
      based clinical guideline.

PMID- 11515417
TI  - Epidemiologic studies of childhood leukemia in Green Bay, Wisconsin.

PMID- 11515418
TI  - Small particulate debris adhering to cell surfaces in human leukocyte cultures:
      relationship with presence of herpes-type virus particles.

PMID- 11515419
TI  - Virus particles in tissue cultures of a human liposarcoma.

PMID- 11515420
TI  - Virus-induced regression of tumor growth.

PMID- 11515421
TI  - Induction of tumors in hamsters by rat Rous sarcoma RBI, producing chick sarcoma
      virus. I. Continuous production of virus oncogenic for chicks by hamster sarcoma
      cells.

PMID- 11515422
TI  - Infectious mononucleosis--always a primary infection with herpes-type virus?

PMID- 11515423
TI  - Effect of ICRF159 on the mammalian cell cycle: significance for its use in cancer
      chemotherapy.

PMID- 11515424
TI  - Characteristics of long-term marmoset cell cultures spontaneously altered or
      transformed by Rous sarcoma virus.

PMID- 11515425
TI  - Rauscher viral leukemogenesis in BALB/c mice treated with rabbit antimouse
      thymocyte serum.

PMID- 11515426
TI  - Mitotic circadian rhythm in a fast-growing and a slow-growing hepatoma: mitotic
      rhythm in hepatomas.

PMID- 11515427
TI  - Host-induced changes in infectivity of Friend spleen focus-forming virus.

PMID- 11515428
TI  - Antibody patterns in different human sera against intracellular and membrane
      antigen complexes associated with Epstein-Barr virus.

PMID- 11515429
TI  - Glucolysis during culture of neoplastic and non-neoplastic murine cell lines
      under aerobic and anaerobic conditions.

PMID- 11515430
TI  - Antigenic properties of a nonreleaser neoplasm induced in the mouse by murine
      sarcoma virus.

PMID- 11515431
TI  - Nutrition of mouse ascites tumor cells in primary culture. I. Large molecular
      substances and conditioned media.

PMID- 11515432
TI  - Kinetics of dimethylamine nitrosation in relation to nitrosamine carcinogenesis.

PMID- 11515433
TI  - Structure-activity relationships among some polynuclear hydrocarbons and their
      hydrogenated derivatives.

PMID- 11515434
TI  - Sarcoma-specific antigens: detection by complement fixation with serum from
      sarcoma patients.

PMID- 11515435
TI  - Attempts to detect nodule-inducing virus in strain RIII mice.

PMID- 11515436
TI  - Cancer mortality among diabetics.

PMID- 11515437
TI  - Appearance of glandlike structures in the tracheobronchial tree of aging mice.

PMID- 11515438
TI  - Preferential localization of gallium-67 citrate in tissues of leukemic mice.

PMID- 11515439
TI  - Two-step mechanism of tumor graft rejection in syngeneic guinea pigs. II.
      Initiation of reaction by a cell fraction containing lymphocytes and neutrophils.

PMID- 11515440
TI  - Amyloidosis in wild house mice during inbreeding and in hybrids derived from
      inbred strains and wild mice.

PMID- 11515441
TI  - Detection of humoral antibody response to polyoma tumor-specific cell-surface
      antigen.

PMID- 11515442
TI  - Role of nonimmunized macrophages in the rejection of an allotransplanted
      lymphoma.

PMID- 11515443
TI  - Statistical analysis of cytogenetic data in cervical neoplasia.

PMID- 11515444
TI  - Multiplication of viruses in Burkitt lymphoma cells.

PMID- 11515445
TI  - Australia antigen (a hepatitis-associated antigen) in leukemia.

PMID- 11515446
TI  - Separation of cells from a mast cell tumor on density gradients of colloidal
      silica.

PMID- 11515447
TI  - Attenuation of Marek's disease virus and study of its properties in two different
      cell cultures.

PMID- 11515448
TI  - Anaerobic glycolysis and patterns of glycolytic intermediates during liver
      carcinogenesis and in hepatoma.

PMID- 11515449
TI  - Immunogenic properties of reticulum cell sarcomas of SJL/J mice.

PMID- 11515450
TI  - Pathologic and virologic studies of tumors induced in mice by two strains of
      murine sarcoma virus.

PMID- 11515451
TI  - Composition studies on tobacco. XLI. Carcinogenesis assay of subfractions of the
      neutral fraction of cigarette smoke condensate.

PMID- 11515453
TI  - Normal and pathologic anatomy of the adrenal gland of the mouse, including
      neoplasms.

PMID- 11515452
TI  - Inhibition of phytohemagglutinin- and alloantigen-induced lymphocyte stimulation
      by Rauscher leukemia virus.

PMID- 11515454
TI  - [Reasons for choosing surgery in abdominal hernia].

PMID- 11515455
TI  - [Structure of the venous wall of the pampiniform plexus in idiopathic
      varicocele].
AB  - The Authors discuss about some histologic patterns observed in 100 pampiniform
      plexus specimens of patients who underwent direct scrotal surgery for idiopathic
      varicocele. Tunica media was involved in all of 81 specimens in which Authors
      observed a vascular wall thickening. Out of these, localized hypertrophic
      phenomena, leading to segmental vascular obliteration, prevailed (74%) on
      widespread forms (26%). In advanced focal localizations subintimal fibrous pads
      were demonstrated. In 96% of cases hypertrophy affected the muscular layer too,
      respectively in focal (41%) and diffuse (59%) way. In 85% of cases fragmentation
      of lamina elastica interna was associated to media hypertrophy. In 69%, venous
      lumen was dilated, frequently in association with wall thickening, while only in
      12 specimens all vascular layers were reduced. Occlusive endoluminal thrombi were
      evident in 12%. At last the Authors underline how the wall pathologic
      modifications do not involve all the veins within the same plexus, and stress on
      the possible physiopathologic relationships between this fact and different
      haemodynamic and clinic conditions.

PMID- 11515456
TI  - Uncommitted gastrointestinal stromal tumour. Case report.
AB  - Gastrointestinal Stromal Tumours (GIST) are mesenchymal tumours with uncertain
      prognosis. Malignant variety represents about 2.0% of malignant gastroenteric
      tumours. The Authors report a clinical case of malignant gastric and
      duodenojejunal GIST, in which the only surgical treatment seems to be definitive.
      R. S., a 69-year-old female, was admitted for asthenia and fever in January 1997.
      Endoscopic exploration, ultrasonography and CT-scan of the abdomen demonstrated
      an exophytic tumour in the greater gastric curvature and one tumour of 5.5 cm of
      diameter in the Treitz's angle. We performed a resection of the gastric tumour
      and the duodenojejunal angle. Postoperative course was uneventful and the patient
      was discharged after 14 postoperative hospital days. Histological analysis showed
      two spindle cells stromal tumours with mitotic rate > 20/10 HPF. The
      immunohistochemistry demonstrated the uncommitted origin of tumour cells. The
      patient refused the chemotherapy treatment. There was no local recurrence or
      metastasis at a follow up of 47 months, in spite the high malignancy degree. For
      this reason and because of the uncertain behaviour of benign GIST, the authors
      propose a lifelong follow up of the patients managed with potentially curative
      surgical resection.

PMID- 11515457
TI  - [Pulmonary hernia].
AB  - Chest-wall hernia is a very unusual pathological event. The Authors report a
      singular diagnostic case of chest-wall hernia, miming rib tumor. Instrumental
      diagnostic tools and surgical treatment is reported. Finally patient's follow-up
      is discussed.

PMID- 11515458
TI  - [Single asymptomatic splenic metastasis of breast carcinoma: report of a clinical
      case].
AB  - The spleen is rarely involved from metastatic disease. Metastases from breast
      cancer are extremely rare although described in the Literature. The Authors
      report a case of a woman who had undergone to radical mastectomy for breast
      cancer nine years previously and admitted to the hospital because of a single
      splenic lesion shown by U.S. scan during the follow up.

PMID- 11515459
TI  - [Intestinal angiodysplasia].
AB  - Intestinal angiodysplastic lesions represent one frequent source of gastro
      enteric tract serious bleedings, endowed with present-day therapeutic
      implications. The Authors report a singular case of a bleeding of this kind. A
      selective arteriography analysis of the superior mesenteric artery immediately
      pointed out the necessity for a surgical intervention, which however has not
      proved being resolutive for recovery, because massive intestinal hemmorrhage
      recurrence occurred. The left gastric artery anomalous origin, being discovered
      in the first branch of the mesenteric artery, which was not recognized fully in
      advance, stressed, in fact, the need for a partial gastrectomy, firstly, and a
      full gastrectomy, subsequently. The post-surgery course got more serious for a
      small leak of the oesophageus-digiunal anastomosis and for a serious renal
      failure. NPT and haemodialysis helped to quickly solve those complications. Other
      hemorrhagic events have not occurred anymore, 5 years having passed since the
      surgical intervention.

PMID- 11515460
TI  - [Diaphragmatic trauma: retrospective analysis of 25 patients].
AB  - Traumatic diaphragmatic injuries are increasing and they must be considered in
      every thoraco-abdominal trauma. The Authors carried out a retrospective analysis
      of 25 cases, whose diagnosis was often difficult due to the predominant clinical
      effects of associated injuries. All patients underwent surgical operation with
      laparotomy to achieve reduction of herniated viscera and repair of the
      diaphragmatic lesion.

PMID- 11515461
TI  - [Fournier syndrome: report of a clinical case].
AB  - The case of a Fournier's syndrome in a 58 years old patient is reported from the
      Authors that describe the ethiopathogenetic and therapeutic aspects. They analyse
      the importance of an early surgical treatment associated with antibiotic therapy
      and later a riparation of the lesions with a myocutaneous skin flap of TLF.

PMID- 11515462
TI  - [Acute colonic pseudoobstruction: physiopathology and treatment].
AB  - The acute colonic pseudo-obstruction is a rare condition. Pathophysiological
      knowledges, nowadays, are still discussed. Several associated pathological
      conditions (cardiological, neurological, metabolic) would mainly cause, with
      different mechanisms, a sympathetic-parasympathetic imbalance. In Authors'
      experience with 19 patients the sudden onset and the rapid evolution to a serious
      condition set the difference with a mechanical obstruction. The radiological
      control was essential to the therapeutic options. The endoscopic decompression
      was successful in 2 cases; the tube cecostomy was effective in 13; the right
      emycolectomy was necessary in 1 case with multiple diastasic cecal perforations.
      Mortality rate: 3 patients (15.70%).

PMID- 11515463
TI  - [Surgical treatment of isolated adrenal metastasis from lung carcinoma].
AB  - A surgical treatment of patients with lung cancer non-microcitoma and isolated
      adrenal metastasis has been reported in literature although limited in number and
      follow up. The Authors report 12 cases of patients operated for lung cancers non
      microcitoma and isolated adrenal metastasis. One patients was lost in the follow
      up, two patients died 3 and 6 months after the adrenalectomy. The other patients
      are alive after 88, 39, 36, 17, 13 months after the adrenalectomy. Four of these
      patients are also disease free. Other 4 patients, more recently operated, are
      alive and disease free after 3, 3, 9 and 9 months after the adrenalectomy. The
      Authors believe that a surgical treatment is justified in these patients,
      considering the results of the series reported in literature and also their own
      results.

PMID- 11515464
TI  - [Combined diagnosis in breast carcinoma: preoperative role of mammoscintigraphy
      with Tc99m-sestamibi. Our Experience].
AB  - The Authors, taking recent literature on tumoral pathology breast studies in to
      consideration, studied a group of patients with a node or a suspect adenous zone
      by clinical and instrumental examination with mammoscintigraphy. 22 patients were
      selected by clinical examination, mammography and ultrasonography. A
      mammoscintigraphy (Tc 99m Sestamibi) was performed before the surgical operation.
      The histologic examination revealed 14 cases of breast cancer; 12 of these (86%)
      resulted positive after scintigraphy, while 2 were false negative. In this study,
      the scintigraphic exam and its diagnostic accuracy were analyzed, both in
      relation to anatomical structure of the mammary gland (thick breast, fibrocystic
      mastopathy, postsurgical scars, etc.) and also in relation to characteristics of
      the suspected node, the nature of which was not possible to determine from other
      exams carried out. In conclusion, after comparison between our experience and
      those reported in literature, we conclude that because of its high specificity
      and sensibility the mammoscintigraphy exam assumes an important comparative index
      in obtaining elements for an additional evaluation when other instrumental
      examinations are dubious.

PMID- 11515465
TI  - [Our experience with the appropriate use of esophagogastroduodenoscopy].
AB  - Many studies emphasize the right indications about the execution of an EGDS
      showing that a lot of requests are inappropriate. We have wanted to report our
      experience too, that showed more comfortable results than that checked, by other
      Authors moreover we have emphasized that the inappropriate requestsare justly
      divided between generical and specialized physicians.

PMID- 11515466
TI  - [Hemorrhoid ligation: a new technique].
AB  - The Author describes an old technique of hemorrhoids' treatment with a new
      disposable instrument: the canadian Patrick O'Regan's Ligator. On a series of 342
      patients, from December 1998 to March 2000, the Author, treating this pathology
      with good results in percentage, stresses on the manageability and practicality
      of this instrument both in the hospital regimen and in the Day Hospital.

PMID- 11515467
TI  - [Reforming health systems, why?].

PMID- 11515468
TI  - [Hospital reform project, objectives, implementation, results and training].
AB  - Face to structural adjustments of the economy, the Tunisian public system of
      health, confronted with internal inefficiencies and to an inadequate financing,
      makes the object of a reform targeting teaching hospitals. Its objectives are to
      institute an autonomy of management and to exploit an integrated system of
      information that, associated to economic studies, will allow the Government to
      revise modes of financing of the health sector. This reform has modified the
      legal structure of university hospitals ending to a management of performances,
      based on the participation of the intervening, in an environment demarcated by
      the Government, by contracting multi-annual programs. By its impact, by reactions
      and surrounding opportunities, its viability and its sustainability are warranted
      especially if one minimizes potential risks linked to the exercise of the
      tutelage and to the adaptation to reforms of the other systems, notably the
      health insurance in order that a project of reform has been adopted and will be
      put in application soon. The strategy of implementation steady has allowed to
      reach convincing results to consolidate and to diagnose insufficiencies to
      fulfill, especially that an adapted extension of this reform is anticipated, to
      the level of regional hospitals, secondary care level.

PMID- 11515469
TI  - [Health insurance in Tunisia, current context and future perspectives].
AB  - The Tunisian health system, notably in its health insurance component, has
      allowed to record a satisfactory evolution of health indicators. Nevertheless,
      socio-economic, demographic and epidemiological transitions impose a global
      reform of the system, notably of its financing. The present article, leaving from
      the presentation of the current system of coverage of the social security
      insured, analyses observed insufficiencies that have brought public authorities
      to commit the health insurance reform. The main observed insufficiencies refer to
      the multiplicity of regimes and their heterogeneity, generating iniquities
      between insured and a strong growth of care expenses financed directly by
      households. In addition, relationships of social security bodies with public and
      private providers of health care are little transparent, marked by a preferential
      processing of public structures, despite an important development of the private
      sector. In a second part, the author analyzes successively objectives of the
      health insurance reform of the social security regimes, its founder principles,
      characteristics of the proposed regime (a mandatory basic regime and an optional
      complementary regime) and sketches of providers payment methods.

PMID- 11515470
TI  - [Implementation of health insurance reform].
AB  - Authors expose in the first part of this article practical modes to implement the
      health insurance reform under the angle of the mastery of care expenses, at the
      micro and the macroeconomic levels. Thus they pass in review the different
      possibilities to master expenses, at the supply and the demand sides, by
      identifying advantages and risks of each of they and by specifying orientations
      of the health insurance reform in this area: the moderating ticket, contractual
      payment methods of hospitals and health professionals, the path of care, the
      refund of care expenses, the rationalization of consumption of medicines and
      complementary examinations and the harmonious development of care supply by a
      better public and private mix. A particular accent is put on preliminaries and
      implementation conditions of the prospective payment of providers and
      organizational conditions of care provision, from general practitioner that would
      become the main entry of the care system. In a second part, authors pass in
      review organization and management conditions of social security bodies, needed
      for the health insurance reform implementation. On the basis of decentralization
      and a three levels organization (local, regional and central), social security
      bodies will put in place the most appropriate organization to insure a steady
      efficient implementation of the health insurance reform, in dialogue with
      stakeholders. Consultative committees at regional and central levels, regrouping
      all the intervening in the health insurance, will be instituted. The sought-after
      objective through this organization is to administer the health insurance, at the
      strategic, decisional and operational levels, with suppleness, as a changing and
      dynamic project, in function of flexibility imperatives necessary for the reform
      implementation.

PMID- 11515471
TI  - [Sickness risk coverage of the poor and low income population].
AB  - Among regimes of sickness risk coverage, those who are managed by the government
      to the profit of the poor and low income population offer advantages in nature,
      in the form of total exempt from payment or a strong subsidy of care in public
      sanitary structures of the ministry of public health. These two regimes, known as
      "Gratuitous Medical Assistance", existed under other names since the 1950's and
      has undergone various modifications that had all for objective to adapt the
      benefit of the gratuitous of care to the economic conditions and financial of the
      targeted population.

PMID- 11515472
TI  - [Health care supply regulation].
AB  - In the current context of health systems' reforms, the regulation would have to
      occupy a major place in the new role of the State concerning health in order that
      the system could reach the essential objective to control the quantity and the
      distribution of health services and to insure an optimal, efficient and equitable
      coverage of the population's needs. Authors pass in review, in a first part,
      current regulation means of health care supply, public and private, put in place
      in Tunisia and suggest their development in areas not covered yet; notably these
      in relation with the quality and the cost-containment of health care. The current
      regulation is interested especially in areas of the infrastructure, equipment,
      medicines and pharmaceutical products and financial and human resources of the
      sector. In a second part, means of regulation of health care supply are exposed
      and could serve as basis to the reform of the current health system. It is thus
      the mastery of the medical demography, incentives for health care providers,
      payment systems, fees and rates of professionals and the free choice and the
      managed competition between providers. Authors conclude by the necessity to
      promote patients' rights in the health system and to valorise its human
      resources, through the development of information on performances of providers
      and the continuous training of professionals.

PMID- 11515473
TI  - [Medical studies in Tunisia].
AB  - In this report, the author analyses the Tunisian medical studies following their
      main stages of evolution, since the creation of the first medical university
      (1963), and focus on the major reforms. A great interest was designed to evaluate
      the comity findings reforms, held during the 1990, which has lead to undertake
      many measures for the medical studies. The author expose the measures applied,
      since 1990 in his report.

PMID- 11515474
TI  - [Perspectives of the Tunisian health system reform].
AB  - Perspectives of development of the Tunisian health system are presented, in
      reference to the conceptual framework recommended by the World Health
      Organization, while a project of health insurance reform of the social security
      regimes is submitted to a dialogue with the different concerned parts.
      Recommended orientations articulate around five axes: 1. The promotion of care
      provision by improving the accessibility to services, notably in zones under
      served, by introducing new modes of dispensation, organization and management of
      care provision in the framework of a continuous quality assurance strategy. 2.
      The financing of health care, with the implementation of the health insurance
      reform, has to allow an improvement of the financial accessibility of the
      population to health care, while supervising the evolution of total health
      expenditures and by developing the system's management capacities. 3. Proposals
      relative to the mobilization of resources are advanced in areas of medicine,
      training of health professionals and research on the health system. 4. Adaptation
      of the health system governance to the new context is necessary and would have to
      be developed around evolving standards for the health system, on evaluation of
      its performances and on information and communication with its users. 5. The
      health system responsiveness, new motion whose contours are again blurred, would
      have to be analysed and adapted to the specific context of the country.

PMID- 11515475
TI  - [Perioperative period: some guidelines: critical analysis of the adopted
      methodology].

PMID- 11515476
TI  - [Apoptosis].

PMID- 11515477
TI  - [Scorpion envenomation].

PMID- 11515478
TI  - [Incidentally discovered adrenal masses].
AB  - The result of the more wide spread use of abdominal imaging procedures has lead
      to reveal more incidentally discovered adrenal masses. In this review we
      evaluated the different biological an radiologic procedures to explore such
      tumors. We finally, presented a proposal of diagnostic and therapeutic algorithm
      for patients with incidental adrenal mass.

PMID- 11515479
TI  - [Carotid stenosis: indications and therapeutic approach].
AB  - There has not been a peripheral vascular surgical procedure subject to as
      exquisite scruting as carotid endarterectomy. The last decade gave a new attitude
      after the analysis and conclusions of the North American Symptomatic Carotid
      Endarterectomy Symptomatic extracranial lesions were best managed with operative
      intervention rather than antiplatelet treatment alone. Now, in the first decade
      of the new millenium, we are embarking on yet another test of carotid
      endarterectmy--a comparison with percutaneous angioplasty and stenting, which is
      a most rigorous contest because endarterectomy must now withstand comparison with
      another "active treatment" rather than the more passive observational modality of
      antiplatelet therapy. The topic of the authors was to provide a panorama of the
      contemporay treatment of carotid disease at this pivotal point in the life cycle
      carotid endarterectomy.

PMID- 11515480
TI  - [Varicocele: endoscopy versus surgery].
AB  - Varicocele is a frequent and benign pathology, well known since the antiquity,
      his treatment has progressed by a better acquaintance of physiology and the
      effects on fertility. In the surgery department of FSI hospital, we compared the
      results of 2 surgical methods: the Ivanisevich's technique (open surgery) and the
      laparoscopic approach. The objective was to compare morbidity, recurrence rate,
      hospital stay, and effects on pains and fertility. From May 1993 to December 1998
      we treated 72 patients with symptomatic varicocele: 40 patients by laparoscopy
      and 32 by open surgery. The recurrence rate was of 32% for surgery and 21% for
      laparoscopy. But duration of surgical operation was longer for laparoscopy: 50 mn
      against 30 mn for unilateral cure and 70 mn against 55 mn for bilateral cure. We
      did not observe a difference between the 2 groups in hospital stay, morbidity,
      pains and fertility. At the end of the study we propose laparoscopy for bilateral
      cure and open surgery for unilateral. Decrease of recurrences needs the
      realisation of a phlebography before surgery, but this investigation weight
      routinely "take charge" of patients; we reserve it to recurrences. Echography
      coupled to Doppler is essentially used for preoperative diagnosis of varicocele
      and for surveillance of postoperative recurrences.

PMID- 11515481
TI  - [Mucopolysaccharidoses in children. Experience of a general pediatric service. 11
      cases].
AB  - The mucopolysaccharidosis are hereditary diseases. The neurological attack
      constitutes the principal factor of gravity of these affections. We conducted a
      retrospective study over a period of 12 years (1988-1999) in the pediatric
      department of Sfax University Hospital. This study allowed us to observe 11 cases
      of mucopolysaccharidosis confirmed by an enzymatic proportioning, with 3 cases of
      Hurler disease (IH), 3 cases of the disease of sanfilippo, (two II A and one III
      B), 3 cases of the disease of Morquio A (type IVA) and 2 cases of the disease of
      Maroteaux Lamy (type VI). A sex ratio of 1.75. The parents were cousins in 90% of
      the cases. The age of revelation ranged between 6 months to 4 years. The clinical
      examination has found a staturo-pondral delay in 81.8% of the cases, a
      craniofacial dysmorphy in 100%, deformations of the rachis in 63.6% of the cases,
      a psychomotor regression in 54.5% of the cases, a medullary compression in 18% of
      the cases, hepatosplenomegaly in 36.4%, and corneal opacities in 45.4% of the
      cases. The therapeutic treatment was limited to the symptomatic measures with
      genetic consulting and antenatal diagnosis.

PMID- 11515482
TI  - [Visceral leishmaniasis in immunocompetent children: diagnostic and epidemiologic
      value of peripheral leishmania blood culture].
AB  - Utilisation of new diagnosis means and particularly non invasive oues in visceral
      leishmaniasis can be very valuable for the biologist, the clinician as well as
      the patient. In this, detection of leishmania in peripheral blood, well know for
      VIH patients, has been applied to 37 immunocompetent tunisan children suffering
      from kala azar that has been shown through direct examination of bone marrow.
      Observed results show that culture on NNN peripheral blood medium was positive in
      25 cases (67.57%). On the other side, detection of leishmania through concomitant
      culture of blood and marrow bone for 24 children with visceral leishmaniasis
      match the results in 75% of the cases. Detection of leishmania by mean of blood
      culture for immunocompetent children is a diagnosis mean of visceral
      leishmaniasis and has also an epidemiologic utility by isoenzymatic
      characterization of isolated leishmania strains.

PMID- 11515483
TI  - [Endometrial ossification. 6 cases].
AB  - Endometrial ossification is a rare and benign pathology. The etiopathogenesis of
      this pathology is controversial. Findings suggestive of diagnosis are fairly well
      know, menstrual irregularities is the main clinical symptoms, expulsion of bony
      fragments is a rare but pathognomonic event. Pelvic ultrasonography suggested an
      intrauterine foreign body and hysteroscopy was necessary to make the correct
      diagnosis. Six cases of endometrial ossification diagnosis and treated at
      obstetrics and gynaecology department A of centre of La Rabta teaching hospital
      (Tunis) are reported.

PMID- 11515484
TI  - [Comparison of ultrasonographic and hysteroscopic results in perimenopausal
      metrorrhagias].
AB  - 84 perimenopausal women with uterine bleeding underwent transvaginal
      ultrasonography and hysteroscopy. Sonographic and hysteroscopic findings have
      been evaluated on the basis of specimens obtained from either endometrial biopsy,
      hysterectomy or operative hysteroscopy. Sensitivity, specificity, positive and
      negative predictive value of hysteroscopy and transvaginal ultrasonography were
      calculated. Hysteroscopy had 91.6% sensitivity, 83.3% specificity, 93.2% positive
      predictive value and 80% negative predictive value in the diagnosis of
      intrauterine abnormality, whereas transvaginal ultrasonography had only 67.3%
      sensitivity, 87.5% specificity, 89.7% positive predictive value and 62.2%
      negative predictive value. In consequence hysteroscopy is better than
      transvaginal sonography concerning only the sensitivity (p < 0.01). Transvaginal
      ultrasonography seems to be an excellent initial diagnostic method, but
      hysteroscopy is a highly accurate means of diagnosing the cause of excessive
      uterine bleeding.

PMID- 11515485
TI  - [Epidemiology of urinary infections in the Menzel-Bourguiba region: 933 cases].
AB  - The author presents a study about epidemiology of urinary tract infection (UTI)
      diagnosed in Menzel-Bourguiba hospital laboratory. These UTI are frequent (933 in
      18 months) and often concern ambulatory practice (63.4%). UTI in hospital (36.6%)
      are most frequent in internal medicine unit (15.9%) and in pediatric unit (7.2%).
      The UTI are most frequent in female gender (sex ratio F/H = 3.0). The most
      frequent isolates are Enterobacteriacae family (91.7%), and E. coli the major
      species (73.7%). Resistances to beta-lactams are frequent either concerning
      hospital strains or ambulatory patients strains. Beta-lactams family are the most
      used antibiotics (80% of prescriptions). In hospital, some isolates were shown to
      possess extended spectrum betalactamase, but these strains became confined in the
      unit where appear because of the architectural conception of the hospital
      (pavilion system). Aminoglycosids and fluoroquinolones are very active
      antibiotics, but cotrimoxazole resistance is frequent. Consequently, before any
      prescription, it would be necessary an antimicrobial susceptibility study, either
      for hospital UTI, or for UTI in ambulatory practice.

PMID- 11515486
TI  - [Congenital Valsalva sinus aneurysm opening into the right ventricle. Two
      operated cases].
AB  - Congenital sinus of valsalva aneurysm is a rare cardiac lesion. Once the aneurysm
      has ruptured, a large left-to-right shunt is created. Prognosis is grave unless
      operative intervention is undertaken. The authors present 2 cases (2 male) of
      congenital aneurysm of the right sinus of valsalva ruptured into the right
      ventricle. The first patient (52 years) have a history of strenuous exertion
      followed by acute precordial pain and dyspnea. The second patient (25 years) was
      asymptomatic. The diagnostic was made by 2D and color doppler echocardiography.
      The defect was closed with a patch with good postoperative course. The authors
      emphasise the possible rupture of the congenital aneurysm of the sinus of
      valsalva after 50 years of age. Echocardiography is certainly the best method for
      diagnosing the condition and for following up these patients. The prognosis after
      surgical repair has usually been satisfactory.

PMID- 11515487
TI  - [Anterior luxation of the elbow. A case report].
AB  - We report in this work a case of anterior pur dislocation of elbow in a patient
      of 45 years, with antecedent of elbow trauma in childhood, occurred after a
      direct trauma on bent elbow. The diagnosis is obvious and represented by a
      pseudarthrosis of the epitrochlea. The treatment consisted of a reduction
      practiced immediately of the dislocation and contention by a posterior plaster
      for two weeks. The consequences are good without recidivism with a latenesis over
      one and half year.

PMID- 11515489
TI  - [Carcinomatous meningitis revealing a cancer: study of two cases].
AB  - Meningeal Carcinomatosis (MC) is rare (4 to 5% of patients with solid tumors). We
      report two cases. The first case is a 53 year-old man presenting flaccid
      paraplegia and the second is a 76 year-old man presenting a clinical picture
      suggestive of normal pressure hydrocephalus. In the two cases, the diagnosis of
      MC was achieved by the demonstration of malignant cells in the CSF. Prognosis was
      poor in the two cases. The clinical presentation of MC is non specific and the
      diagnosis is only confirmed by demonstrating carcinomatous cells in CSF.

PMID- 11515488
TI  - [Gastric adenocarcinoma secondary to Hodgkin's disease treatment].
AB  - Second malignant neoplasms are a major cause of late morbidity and mortality
      following treatment for Hodgkin's disease. Gastric carcinoma belong to the rare
      secondary malignancies induced by radiation-therapy and it is associated with a
      poor prognosis. We report a patient treated for Hodgkin's disease by 6 ABVD and
      total lymphoid radiation therapy, who developed a gastric carcinoma 9 years after
      completing treatment. Our case fits the criteria for radiation induced
      malignancies reported from the literature: IN CONCLUSION: recommendations are
      presented for both prevention and early detection of the tumours we recommend a
      strict follow-up for patients treated for HD to detect second cancers.

PMID- 11515490
TI  - [Male pseudo-hermaphroditism due to partial 5 alpha-reductase deficiency, a case
      report].
AB  - Male pseudo hermaphroditism caused by steroid 5 alpha reductase deficiency is a
      rare autosomal recessive disorder. This enzyme catalyses the conversion of
      testosterone to dihydrotestosterone (DHT) in genital tissue. The potent androgen
      DHT is required for full masculinization of the external genitalia hence,
      masculinization defects of varying degree result from diminished DHT formation.
      We report a Tunisian patient who was raised as a girl, presented to us at the age
      of 15, because male phenotype had become predominant at puberty. Endocrinological
      investigations revealed an in crease in the ratio serum testosterone/DHT = 17.
      Treatment with dihydrotestosterone and surgical correction, after psychological
      evaluation permitted the change of gender identity to male.

PMID- 11515491
TI  - Have the National Health Care System recommendations influenced the move of
      Italian General Practitioners towards the management of Helicobacter pylori
      infection?

PMID- 11515492
TI  - Zinc, ammonia, and Helicobacter pylori infection in liver cirrhosis.

PMID- 11515493
TI  - Diet and cardiovascular diseases.

PMID- 11515494
TI  - Applications of manipulative techniques.

PMID- 11515495
TI  - High-frequency jet ventilation.

PMID- 11515496
TI  - A statement of homocyst(e)ine and cardiovascular disease.

PMID- 11515497
TI  - Intensive surveillance and treatment of dyslipidemia in the postinfarct patient:
      evaluation of a nurse-oriented management approach.

PMID- 11515498
TI  - The Y-family of DNA polymerases.

PMID- 11515499
TI  - Anxiolytic-like action of diazepam: which GABA(A) receptor subtype is involved?

PMID- 11515500
TI  - Bibliography. Current world literature. Hyperlipidaemia and cardiovascular
      disease.

PMID- 11515501
TI  - Folic acid and human malformations: misunderstandings.

PMID- 11515503
TI  - Do plants have more genes than humans? Yes, when it comes to ABC proteins.

PMID- 11515502
TI  - Vitamin A teratogenicity and risk assessment in the macaque retinoid model.

PMID- 11515504
TI  - Application of the double needle technique to CT-guided thoracic sympathetic and
      splanchnic plexus blocks.

PMID- 11515505
TI  - MRI features of primary central nervous system lymphomas at presentation.
AB  - Pretreatment MRI examinations of 40 immunologically competent patients with
      primary CNS lymphoma (PCNSL) were evaluated (24 men, 16 women, median age 63
      years). Seventy lesions were found (mean size: 19.9 mm). The number of lesions
      ranged from one (n = 25) to six (n = 1). The most frequent locations were the
      cerebral hemispheres (n = 22), the corpus callosum (n = 11), and the basal
      ganglia (n = 11). Cerebellar manifestations were found in 10 patients. Ocular (n
      = 2) and medullary cord (n = 1) manifestations were rare. Contrast enhancement
      was encountered in all lesions. Although 39 patients had lesions adjacent to the
      CSF space, leptomeningeal spread was only present in five patients. Necrosis was
      seen in two lesions only. Edema was extensive in 24 patients, moderate in 11
      patients, and absent in five patients. Contrast-enhancing lesions in contact with
      the subarachnoid space and without necrosis are characteristic of PCNSL.

PMID- 11515506
TI  - Broad-spectrum antibiotics in ORACLE.

PMID- 11515507
TI  - Broad-spectrum antibiotics in ORACLE.

PMID- 11515508
TI  - Broad-spectrum antibiotics in ORACLE.

PMID- 11515509
TI  - Broad-spectrum antibiotics in ORACLE.

PMID- 11515510
TI  - Poliovirus immunisation in the Democratic Republic of the Congo.

PMID- 11515511
TI  - Multiple vaccination.

PMID- 11515512
TI  - Maternal mortality in East Timor.

PMID- 11515513
TI  - Adverse effects of nevirapine.

PMID- 11515514
TI  - Adverse effects of nevirapine.

PMID- 11515515
TI  - Nappies and transmission of Giardia lamblia between children.

PMID- 11515516
TI  - Early detection of malignant change in breast cells.

PMID- 11515517
TI  - Serum cholesterol and haemorrhagic stroke.

PMID- 11515519
TI  - Thyrotropin as first-line thyroid test.

PMID- 11515520
TI  - Preictal signs on electroencephalography.

PMID- 11515521
TI  - Selective cyclo-oxygenase inhibitors.

PMID- 11515522
TI  - Choosing our own reviewers.

PMID- 11515523
TI  - National Health Service fails prisoners.

PMID- 11515524
TI  - Help with tobacco control.

PMID- 11515525
TI  - New aspects of physiological and pathophysiological functions of adenosine A2A
      receptor in basal ganglia.
AB  - There is now growing interest in the functional role of adenosine A2A receptors.
      Their distribution within the brain is restricted in the basal ganglia,
      particularly abundant in the striatum, which are thought to play a crucial role
      in the control of motor behavior. Indeed, newly developed A2A receptor selective
      antagonists have a profound influence on motor functions, with anti-Parkinsonian
      activities in several animal models. Striatal spiny neurons serve as a major
      anatomical locus for the relay of cortical information flow through the basal
      ganglia. The GABA releasing projection neurons represent the A2A receptor
      mediated main target of adenosine. The GABAergic synaptic neurotransmission is
      regulated by adenosine via A2A receptors on the presynaptic terminals. Blockade
      of this modulatory function by A2A antagonists could repair striatopallidal
      abnormal neuronal activities provoked by striatal dopamine depletion in the
      Parkinsonian state. A2A receptor antagonists provide a novel therapeutic
      potential for the treatment of Parkinson's disease.

PMID- 11515526
TI  - Effects of alpha-D-glucosylglycerol on the in vitro digestion of disaccharides by
      rat intestinal enzymes.
AB  - Alpha-D-glucosylglycerol (GG) is a mixture of 2-O-alpha-D-glucosylglycerol (GG
      II), (2R)-1-O-alpha-D-glucosylglycerol (R-GG-I) and (2S)-1-O-alpha-D
      glucosylglycerol (S-GG-I). GG has been found to be slightly hydrolyzed in vitro
      only by rat intestinal enzymes, but hardly at all by other digestive juices. GG
      suppressed the hydrolysis of maltose, sucrose and isomaltose by rat intestinal
      enzymes because the amount of glucose in the digestion of a mixture of GG and
      disaccharide was less than the sum of that in each individual digestion. The
      consumption of GG was suppressed by isomaltose, but promoted by maltose, with the
      hydrolysis of GG being suppressed. Sucrose appeared to suppress only the
      consumption of S-GG-I, suggesting that S-GG-I was hydrolyzed by the active site
      of sucrase in a sucrase-isomaltase complex. Transglucosylation seems to have
      occurred more frequently in the individual digestion of maltose and isomaltose
      than in that of GG and sucrose. GG seemed to promote transglucosylation in the
      presence of maltose, to suppress it with sucrose, and to delay it with
      isomaltose.

PMID- 11515527
TI  - Establishment of a new cross of the rice blast fungus derived from Japanese
      differential strain Ina168 and hermaphroditic rice pathogen Guy11.
AB  - Mating experiments between Magnaporthe grisea Japanese rice pathogens and Guy11,
      a hermaphroditic fertile rice pathogen, were done aimed at identification of
      avirulence genes. A cross named cross 2107 with thirty-six random progenies was
      obtained. Segregation analyses of genetic markers found that the cross was less
      suitable for genetic analysis. Backcrosses with cross 2107 progenies and Guy11
      were done and another cross named cross 5307 with sixty-five progenies was
      obtained. A locus controlling kasugamycin resistance named Ksg1R was identified
      and used for a model case of genetic mapping. Bulked segregant analysis was done
      to find adjacent RAPD markers for mapping of the gene. Three adjacent markers to
      Ksg1R were obtained and a genetic map around the Ksg1R was made, but these
      markers were not located on a single chromosome. These results suggest that
      genetic analysis to identify a gene locus is available in cross 5307. Infection
      assay of parental strains of cross 5307 to Japanese differential rice cultivars
      suggested the possibility of genetic analysis of cultivar specificity toward four
      rice cultivars: Aichi-asahi, Kusabue, Tsuyuake, and K59.

PMID- 11515528
TI  - Isolation and characterization of Desulfitobacterium sp. strain Y51 capable of
      efficient dehalogenation of tetrachloroethene and polychloroethanes.
AB  - A strict anaerobic bacterium, strain Y51, was isolated from soil contaminated
      with tetrachloroethene (PCE). Strain Y51 is capable of very efficiently
      dehalogenating PCE via trichloroethene (TCE) to cis-1,2-dichloroethene (cis-1,2
      DCE) at concentrations as high as 960 microM and as low as 0.6 microM. Strain Y51
      was gram-negative, motile with some lateral flagella, and curved rod-shaped. On
      the basis of the 16S rDNA sequence, the organism was identified to be a species
      within the genus Desulfitobacterium. Strain Y51 also had dehalogenation
      activities toward polychloroethanes such as hexa-, penta-, and
      tetrachloroethanes, from which dichloroethenes were produced as the final
      products. The cell extracts mediated the dehalogenation of PCE with reduced
      methyl viologen as an electron carrier at the specific rate of 5.0 nmol min(-1)
      mg cell protein(-1) (pH 7.2, 37 degrees C). Dehalogenation was highly susceptible
      to air oxidation, and to potential alternative electron acceptors such as nitrite
      or sulfite.

PMID- 11515529
TI  - Synthesis of optically active N-(2-pyridyloxiran-2-ylmethyl) benzenesulfonamide
      derivatives and their herbicidal activity.
AB  - Novel herbicidally active sulfonamide compounds having a 2-arylsubstituted
      oxiranylmethyl structure are racemates due to a chiral carbon in the oxirane
      moiety. To clarify the stereochemical structure-activity relationship, we
      synthesized each enantiomer of 4-chloro-N-[2-(6-chloropyridin-2-yl)-2-oxiran-2
      ylmethyl]-3,N-dimethylbenzenesulfonamide and N-[2-(6-chloropyridin-2-yl)-2-oxiran
      2-ylmethyl]-N-methyl-5,6,7,8-tetrahydronaphthalene-2-sulfonamide by chemical
      methods including Sharpless asymmetric chlorohydroxylation. The results of
      herbicidal tests indicated that the (S)-isomers were the active forms.

PMID- 11515530
TI  - Accelerative effect of olive oil on liver glycogen synthesis in rats subjected to
      water-immersion restraint stress.
AB  - The effects of dietary oils on stress-induced changes in the liver glycogen
      metabolism of male Wistar rats at 6 weeks of age were investigated. The rats were
      subjected to repetitive water-immersion restraint and fed with a 20% saturated
      fatty acid mixture (PSC), olive oil (OLI), safflower oil (SAF), or linseed oil
      (LIS) diet. Stress loading decresed the body weight gain, although the food
      intake was hardly changed, and the weights of the liver and spleen generally
      declined regardless of the elapsed time after stress loading and the type of
      dietary oil. The adrenal weight was generally enhanced by stress in all deitary
      groups, and particularly tended to be greater in the OLI and PSC groups than in
      the other two. The plasma corticosterone concentration increased immediately
      after stressing (Stress-1), but approached the level of the rats with no stress
      (No stress) 2 h after releasing the stress load (Stress-2) in all groups. The
      enhancement of corticosterone level in the Stress-1 animals was large in the PSC
      and OLI groups, and the decline of this level in the Stress-2 animals was small
      in the OLI group when compared with the other groups. Although the concentrations
      of total cholesterol (T-CHOL) and triacylglycerol (TG) in the plasma were
      decreased by stress loading in all groups, these concentrations in the PSC and
      OLI groups were nearly always higher than in the other groups. The liver serine
      dehydratase (SDH) activity enhanced by stress was high in the OLI group and
      tended to be high in the PSC group when compared with the other groups. The
      contents of liver glycogen were reduced in the Stress-1 animals and extremely
      elevated in the Stress-2 animals of all groups, and particularly in the OLI
      group, the reduction in the Stress-1 animals was smaller and the enhancement in
      the Stress-2 animals was greater than in the other groups. These results suggest
      that feeding oleic acid to rats exposed to water-immersion restraint further
      accelerated liver glycogen synthesis through the rise in liver SDH activity due
      to increased corticosterone secretion when compared with the effect from linoleic
      and alpha-linolenic acids.

PMID- 11515531
TI  - Characterization of the replication region of the Lactobacillus reuteri plasmid
      pTC82 potentially used in the construction of cloning vector.
AB  - A 3.2 kb DNA fragment containing the replication region (RR) from pTC82 was
      cloned, sequenced, and found to contain elements typical of plasmids that
      replicate via a rolling-circle mechanism of replication (RCR), including double
      strand origin (DSO), replication protein gene (rep), and single-strand origin
      (SSO). The DSO of pTC82 contains two domains showing 55.5% and 84.6% similarities
      in nucleotide (nt) sequence to the conserved functional elements bind and nic,
      respectively, which are required for the initiation of the leading strand typical
      of the pC194-RCR family. Although the predicted rep gene product of pTC82 (Rep82)
      shares little identity (less than 24%) with other known Reps, a region containing
      three motifs, characteristic of the pC194-family Reps, was identified, indicating
      the Rep82 as a novel Rep protein of this family. Downstream of the rep82 gene,
      strong similarity to the typical palT type-SSO could be detected. This is the
      first palT type-SSO to be identified from Lactobacillus. Through a series of
      deletion studies, the minimal replicon of the cloned RR was found to be 2.66 kb
      in size including the DSO region and rep gene. This RR was further identified as
      being highly stable in L. reuteri and also bearing a very narrow host-range
      property, suggesting it to be a good replicon potentially useful in vector
      construction for developing L. reuteri as a vaccine carrier.

PMID- 11515532
TI  - Visualization of nuclei in Aspergillus oryzae with EGFP and analysis of the
      number of nuclei in each conidium by FACS.
AB  - Aspergillus oryzae has been reported to form conidia with multinuclei. In order
      to analyze nuclei in living cells, we developed an expression system of the A.
      nidutans histone H2B protein tagged by EGFP (H2B::EGFP). In both A. oryzae
      niaD300 and A. nidulans FGSC89 transformants expressing H2B::EGFP, fluorescence
      was detected in nuclear regions of hyphae and conidia. While a conidium contained
      only one fluorescent spot in the A. nidulans transformant, approximately 66% of
      conidia had two, 24% had one, and 10% had three or more in the A. oryzae
      transformant. The conidia expressing H2B::EGFP were put through FACS
      (fluorescence-activated cell sorting) analysis and two sharp peaks, corresponding
      to one and two nuclei in each conidium, were noted in the A. oryzae transformant.
      In addition, the A. oryzae uninucleate conidia that were successfully isolated by
      FACS reproduced conidia with almost the same number distribution of nuclei as
      that of the original. Conidia of five A. oryzae strains used in sake brewing were
      scored for the number of nuclei, showing that a varied number of nuclei existed
      in each conidium and some strains had a small number of uninucleate conidia.

PMID- 11515533
TI  - 1-Aminocyclopropane-1-carboxylate synthase of Penicillium citrinum: primary
      structure and expression in Escherichia coli and Saccharomyces cerevisiae.
AB  - A plant hormone, ethylene, is formed through 1-aminocyclopropane-1-carboxylic
      acid (ACC). A fungus, Penicillium citrinum, was found to synthesize ACC and to
      degrade ACC into 2-oxobutyrate and ammonia. ACC synthase, responsible for ACC
      synthesis in P. citrinum, was characterized on the molecular level by sequencing
      of N terminal and proteolytic peptides of the enzyme, and cloning and sequencing
      of its cDNA. The ACC synthase from P. citrinum had 430 amino acid residues and a
      shorter C terminal than the plant enzyme. The enzyme purified from Escherichia
      coli transformed with ACC-synthase-encoding DNA showed similar properties to
      those of the purified enzyme from P. citrinum. Saccharomyces cerevisiae with ACC
      synthase accumulated ACC in the medium with increasing time of incubation. The
      sequence of ACC synthase from P. citrinum was compared with that of the plant
      enzyme with discussion about important residues for catalysis.

PMID- 11515534
TI  - In vitro biosynthesis of homogalacturonan by a membrane-bound
      galacturonosyltransferase from epicotyls of azuki bean.
AB  - A membrane preparation of 7-d-old seedlings from azuki bean (Vigna angularis)
      contained galacturonosyltransferase (GalAT) capable of transferring galacturonic
      acid (GalA) from UDP-GalA into polygalacturonic acid (PGA) as an exogenous
      acceptor. The enzyme was maximally active at pH 6.8-7.8 and 25-35 degrees C in
      the presence of 5 mM Mn2+ and 0.5% (w/v) Triton X-100. Acid-soluble low-Mr
      (average Mr 10,000) PGA was a more efficient acceptor substrate than acid
      insoluble polymer (Mr 70,000). The apparent Michaelis constants for UDP-GalA and
      low-Mr PGA were 0.14 mM and 0.02 mg/ml, respectively. Various pectins with
      different degrees of methyl-esterification (DE) were poor acceptors, and the
      enzyme activity tended to decrease with decreasing DE of the pectins. The
      transfer products from incubation of the enzyme with UDP-14C-GalA and the low-Mr
      PGA yielded 14C-GalA2 as the major product upon digestion with an
      endopolygalacturonase (EPGase), confirming the incorporation of GalA into PGA
      through contiguous alpha-1,4-linkages.

PMID- 11515535
TI  - In vitro model using mouse hepatocytes for study of alcohol stress.
AB  - In this study, the effects of ethanol and allyl alcohol on primary mouse
      hepatocytes were investigated. No cytotoxicity was observed by ethanol
      treatments, but more toxicity to cells was found in the response to allyl alcohol
      treatment. The expression of cytochrome P450 2E1 (CYP2E1), phase I enzyme was
      examined in response to ethanol and allyl alcohol. Both xenobiotics induced
      CYP2E1 up to 1.5 to approximately 5 fold at the protein level. The effects of
      insulin on CYP2E1 expression were also measured. Insulin, which has been regarded
      as an essential hormone for primary hepatocytes, was shown to decrease the level
      of CYP2E1 protein, and did not affect cell viability. These results on CYP2E1
      induction demonstrate that primary mouse hepatocytes, when using ethanol and
      allyl alcohol as substrates and in insulin-free medium, provide a suitable system
      for the studies of the role of CYP2E1 in xenobiotic metabolism and toxicity.

PMID- 11515536
TI  - Insecticidal and neural activities of candidate photoaffinity probes for
      neonicotinoid binding sites.
AB  - Photoreactive derivatives of imidacloprid and its nitromethylene analogue were
      synthesized as candidate photoaffinity probes for identifying the amino acid
      residues of nicotinic acetylcholine receptors (nAChRs) that interact with the
      neonicotinoid insecticides. When the candidate probes were injected into American
      cockroaches, the nerve cord neural activity initially increased, then ceased and
      death of the insect followed. Both the nerve cord and toxicity were enhanced by
      changing the photoreactive substituent from the para position to the meta
      position on the spacer benzyl moiety. When tested on a Drosophila SAD/chicken
      beta2 hybrid, recombinant nAChR expressed in Xenopus oocytes, the nitromethylene
      candidate probes showed agonist activity similar to that previously observed for
      imidacloprid.

PMID- 11515537
TI  - Identification of amino acid residues essential for the substrate specificity of
      Flavobacterium sp. endo-beta-N-acetylglucosaminidase.
AB  - The gene encoding the endo-beta-N-acetylglucosaminidase from Flavobacterium sp.
      (Endo-Fsp) was sequenced. The Endo-Fsp gene was overexpressed in Escherichia coli
      cells, and was purified from inclusion bodies after denaturation by 8 M urea. The
      renatured Endo-Fsp had the same optimum pH and substrate specificity as the
      native enzyme. Endo-Fsp had 60% sequence identity with the endo-beta-N
      acetylglucosaminidase from Streptomyces plicatus (Endo-H), and the putative
      catalytic residues were conserved. Site-directed mutagenesis was done at
      conserved residues based on the three-dimensional structure and mutagenesis of
      Endo-H. The mutant of Glu-128, corresponding to Glu-132 in Endo-H and identified
      as an active site residue, was inactivated. Mutagenesis around the predicted
      active site of Endo-Fsp reduced the enzymatic activity. Moreover, the hydrolytic
      activity toward hybrid-type oligosaccharides was decreased compared to that
      toward high-mannose type oligosaccharides by mutagenesis of Asp-126 and Asp-127.
      Therefore, site-directed mutagenesis of some of these conserved residues
      indicates that the predicted active sites are essential to the enzymatic activity
      of Endo-Fsp, and may have similar roles in catalysis as their counterparts in
      Endo-H.

PMID- 11515538
TI  - Purification and characterization of aminopeptidase B from Escherichia coli K-12.
AB  - Aminopeptidase B, which is one of the four cysteinylglycinases of Escherichia
      coli K-12, was purified to electrophoretic homogeneity and its enzymatic
      characteristics were observed. Aminopeptidase B was activated by various divalent
      cations such as Ni2+, Mn2+, Co2+, and Cd2+, and lost its activity completely on
      dialysis against EDTA. This indicates that aminopeptidsase B is a
      metallopeptidase. It was stabilized against heat in the presence of Mn2+ or Co2+.
      The activity of aminopeptidase B, which was saturated with one of above divalent
      cations, was enhanced on the addition of a very small amount of a second divalent
      cation. Alpha-glutamyl p-nitroanilide, leucine p-nitroanilide, and methionine p
      nitroanilide were good substrates for aminopeptidase B, while native peptides,
      cysteinylglycine and leucylglycine, were far better substrates. The kcat/Km for
      cysteinylglycine was much bigger than those for leucylglycine or leucine p
      nitroanilide.

PMID- 11515539
TI  - First stereoselective synthesis of (+)-magnostellin C, a tetrahydrofuran type of
      lignan bearing a chiral secondary benzyl alcohol.
AB  - (+)-Magnostellin C, which is a tetrahydrofuran type of lignan bearing a chiral
      secondary benzylic hydroxy group, was stereoselectively synthesized from L
      arabinose by using threo selective aldol condensation.

PMID- 11515540
TI  - In vivo and in vitro analyses of the AmyR binding site of the Aspergillus
      nidulans agdA promoter; requirement of the CGG direct repeat for induction and
      high affinity binding of AmyR.
AB  - The alpha-glucosidase gene (agdA) of Aspergillus nidulans has a single CGGN8CGG
      type AmyR binding site in its promoter region. The binding site is functional in
      vivo as a cis-element responsible for induction by starch, and mutational studies
      indicated that both the CGG triplets are required for high-level induction. A
      part of AmyR (residues 1-411; AmyR(1-411)), which was produced as a MalE fusion
      protein in E. coli, bound to the CGGN8CGG site of the agdA promoter. DNA binding
      profiles to the mutant binding sites that lacked both or either one of the CGG
      triplets suggested that AmyR(1-411) can bind to a single CGG triplet site with
      low affinity and that two AmyR molecules cooperatively bind to the CGG direct
      repeat.

PMID- 11515541
TI  - Molecular cloning, sequencing, and expression of cDNA encoding serine protease
      with fibrinolytic activity from earthworm.
AB  - An earthworm, Lumbricus rubellus, produces alkaline trypsin-like proteases that
      are greater than trypsins in their stability and strong tolerance to organic
      solvents. cDNAs encoding strong fibrinolytic proteases (F-III-2 and F-III-1) in
      the six isozymes were cloned and sequenced to study their stability-structure
      relationship. The cDNAs of F-III-2 and F-III-1 comprised 1011 and 973 bp and
      included open reading frames that encode polypeptides of 245 and 246 amino acid
      residues, respectively. The deduced amino acid sequences of F-III-2 and F-III-1
      have 7 and 8 activation peptides in the N-termini respectively, indicating that
      they are translated as proenzymes and modified to active forms by
      posttranslational processing. They showed similarity to mammalian serine
      proteases and conserved the catalytic amino acid residues, however, neither
      arginine nor lysine residues were present in the autolysis region. The gene
      encoding the native form of F-III-2 was expressed in Pichia pastoris to produce
      and secrete the earthworm protease in the culture medium, which dissolves an
      artificial fibrin plate.

PMID- 11515542
TI  - Structural change and catalytic activity of horseradish peroxidase in oxidative
      polymerization of phenol.
AB  - The effects of solvent and reaction conditions on the catalytic activity of
      horseradish peroxidase (HRP) were investigated for oxidative polymerization of
      phenol in water/organic mixtures using hydrogen peroxide as an oxidant. Also, the
      structural changes of HRP were investigated by CD and absorption spectroscopy in
      these solvents. The results suggest that the yield of phenol polymer (the
      conversion of phenol to polymer) is strongly affected by the reaction conditions
      due to the structural changes of HRP, that is, the changes in higher structure of
      the apo-protein and dissociation or decomposition of the prosthetic heme. Optimum
      solvent compositions for phenol polymerization depend on the nature of the
      organic solvents owing to different effects of the solvents on HRP structure. In
      addition to initial rapid changes, slower changes of HRP structure occur in
      water/organic solvents especially at high concentrations of organic solvents. In
      parallel with these structural changes, catalytic activity of HRP decreases with
      time in these solvents. At higher reaction temperatures, the yield of the polymer
      decreases, which is also ascribed to modification of HRP structure. It is known
      that hydrogen peroxide is an inhibitor of HRP, and the yield of phenol polymer is
      strongly dependent on the manner of addition of hydrogen peroxide to the reaction
      solutions. The polymer yield decreases significantly when hydrogen peroxide was
      added to the reaction solution in a large amount at once. This is probably due to
      inactivation of HRP by excess hydrogen peroxide. From the CD and absorption
      spectra, it is suggested that excess hydrogen peroxide causes not only
      decomposition of the prosthetic heme but also modification of the higher
      structure of HRP.

PMID- 11515543
TI  - A novel screening for inhibitors of a pleiotropic drug resistant pump, Pdr5, in
      Saccharomyces cerevisiae.
AB  - Yeast is an excellent model system of eukaryotes for the study of molecular
      mechanisms of ATP-binding cassette transporters. Pdr5 protein is a yeast
      Saccharomyces cerevisiae ATP-binding cassette transporter conferring resistance
      to several unrelated drugs. Here, we described a novel drug screening system
      designated to detect compounds that inhibit the function of Pdr5. An indicator
      strain with increased drug sensitivity was constructed with an ergosterol
      deficient background (delta syr1/erg3 null mutation). The sensitivity of the
      indicator strain (delta syr1/erg3 delta pdr5 delta snq2) to the Pdr5 substrates,
      cycloheximide and cerulenin, was increased 16-fold and 4-fold against wild type,
      respectively. The screening system is mainly based on the growth inhibition of
      the PDR5-overexpressed indicator strain with the combination of a sample and
      cycloheximide or cerulenin. The effect of an mdr inhibitor, FK506 on the
      screening system was clearly detected even at a low concentration (approximately
      0.5 microg/ml). In addition, accumulation of rhodamine 6G in the cells was
      detected as a result of Pdr5 inhibition by FK506. These results indicated that
      the screening system is useful for a sensitive screening of Pdr5-specific
      inhibitors with low toxicity.

PMID- 11515544
TI  - Characteristics of wine produced by mushroom fermentation.
AB  - Saccharomyces cerevisiae is the main microorganism used in wine brewing, because
      this microbe has potent ability to produce alcohol dehydrogenase. We have
      recently discovered that some genera of mushroom produced alcohol dehydrogenase,
      and made wine by using a mushroom in place of S. cerevisiae. The highest alcohol
      concentration in this wine was achieved with Pleurotus ostreatus (2.6 M, 12.2%).
      In the case of Agaricus blazei, the same alcohol concentration (1.7 M, 8%) was
      produced under both aerobic and anaerobic conditions. This wine produced by A.
      blazei contained about 0.68% beta-D-glucan, which is known to have a preventive
      effects against cancer. The wine made by using Flammulina velutipes showed
      thrombosis-preventing activity, giving a prolonged thrombin clotting time 2.2
      fold that of the control. Thus, the wine made by using mushroom seems to be a
      functional food which can be expected to have preventive effects against cancer
      and thrombosis.

PMID- 11515545
TI  - Effects of double mutation at two distant IgE-binding sites in the three
      dimensional structure of the major house dust mite allergen Der f 2 on IgE
      binding and histamine-releasing activity.
AB  - Recently, we reported that introduction of mutations that induced conformational
      changes of the major mite allergen Der f 2 was an efficient strategy to reduce
      the allergenicity for safer allergen-specific immunotherapy. In this study, we
      evaluated another strategy, disruption of two independent IgE epitopes without
      inducing conformational change. We analyzed allergenicities of the wild-type Der
      f 2, two single mutants with a mutation at either of the two IgE-binding sites
      (K15A and K77A), and a double mutant with mutations at both of the sites
      (K15/77A). Purified recombinant forms of Der f 2 expressed in Escherichia coli
      had correct disulfide bonds, equivalent apparent molecular masses of
      approximately 15 kDa, and similar secondary structures. The mutants of Der f 2
      had less IgE reactivities than the wild-type Der f 2 and reduced inhibitory
      activities for IgE-binding to the wild-type Der f 2. However, the mutations did
      not significantly reduce histamine-releasing activity.

PMID- 11515546
TI  - Purification and substrate specificity of honeybee, Apis mellifera L., alpha
      glucosidase III.
AB  - Alpha-glucosidase III, which was different in substrate specificity from honeybee
      alpha-glucosidases I and II, was purified as an electrophoretically homogeneous
      protein from honeybees, by salting-out chromatography, DEAE-cellulose, DEAE
      Sepharose CL-6B, Bio-Gel P-150, and CM-Toyopearl 650M column chromatographies.
      The enzyme preparation was confirmed to be a monomeric protein and a glycoprotein
      containing about 7.4% of carbohydrate. The molecular weight was estimated to
      approximately 68,000, and the optimum pH was 5.5. The substrate specificity of
      alpha-glucosidase III was kinetically investigated. The enzyme did not show
      unusual kinetics, such as the allosteric behaviors observed in alpha-glucosidases
      I and II, which are monomeric proteins. The enzyme was characterized by the
      ability to rapidly hydrolyze sucrose, phenyl alpha-glucoside, maltose, and
      maltotriose, and by extremely high Km for substrates, compared with those of
      alpha-glucosidases I and II. Especially, maltotriose was hydrolyzed over 3 times
      as rapidly as maltose. However, maltooligosaccharides of four or more in the
      degree of polymerization were slowly degraded. The relative rates of the k0
      values for maltose, sucrose, p-nitrophenyl alpha-glucoside and maltotriose were
      estimated to be 100, 527, 281 and 364, and the Km values for these substrates,
      11, 30, 13, and 10 mM, respectively. The subsite affinities (Ai's) in the active
      site were tentatively evaluated from the rate parameters for
      maltooligosaccharides. In this enzyme, it was peculiar that the Ai value at
      subsite 3 was larger than that of subsite 1.

PMID- 11515547
TI  - Azurin involved in alcohol oxidation system in Pseudomonas putida HK5: expression
      analysis and gene cloning.
AB  - Expression of azurin in Pseudomonas putida HK5 was examined by immunoblot
      analysis. Similar amounts of azurin were found in the cells grown into the
      stationary phase on any carbon sources, including LB medium without alcohol,
      where no quinoprotein alcohol dehydrogenases appeared. In the early exponential
      phase, the highest amount of azurin was found in the cells grown on 1-butanol,
      but here was none in the case of LB medium, suggesting that expression of azurin
      is cooperative with that of the alcohol oxidase system, especially the system
      including quinohemoprotein alcohol dehydrogenase IIB. The azurin gene (azu) was
      cloned and sequenced. azu is monocistronic, and in its promoter region, FNR
      binding consensus sequence was found. However, its relative position suggests
      different transcriptional regulation from that in azu of P. aeruginosa. The
      molecular weight of the mature protein without copper ion calculated from the
      amino acid sequence was consistent with the value of the purified azurin measured
      by mass spectrometry.

PMID- 11515548
TI  - Cloning of a gene cluster encoding enzymes responsible for the mevalonate pathway
      from a terpenoid-antibiotic-producing Streptomyces strain.
AB  - A gene cluster encoding enzymes responsible for the mevalonate pathway was
      isolated from Streptomyces griseolosporeus strain MF730-N6, a terpenoid
      antibiotic terpentecin producer, by searching a flanking region of the 3-hydroxy
      3-methylglutaryl coenzyme A (HMG-CoA) reductase gene, which had been previously
      isolated by complementation. By DNA sequencing of an 8.9-kb BamHI fragment, 7
      genes encoding geranylgeranyl diphosphate synthase (GGDPS), mevalonate kinase
      (MK), mevalonate diphosphate decarboxylase (MDPD), phosphomevalonate kinase
      (PMK), isopentenyl diphosphate (IPP) isomerase, HMG-CoA reductase, and HMG-CoA
      synthase were suggested to exist in that order. Heterologous expression of these
      genes in E. coli and Streptomyces lividans, both of which have only the
      nonmevalonate pathways, suggested that the genes for the mevalonate pathway were
      included in the cloned DNA fragment. The GGDPS, MK, MDPD, PMK, IPP isomerase, and
      HMG-CoA synthase were expressed in E. coli. Among them, the recombinant GGDPS,
      MK, and IPP isomerase were confirmed to have the expected activities. This is the
      first report, to the best of our knowledge, about eubacterial MK with direct
      evidence.

PMID- 11515549
TI  - Is your ribozyme design really correct?: A proposal of simple single turnover
      competition assay to evaluate ribozymes.
AB  - Today, many nucleic acid enzymes are used in gene therapy and gene regulations.
      However, no simple assay methods to evaluate enzymatic activities, with which we
      judge the enzyme design, have been reported. Here, we propose a new simple
      competition assay for nucleic acid enzymes of different types to evaluate the
      cleaving efficiency of a target RNA molecule, of which the recognition sites are
      different but overlapped. Two nucleic acid enzymes were added to one tube to make
      a competition of these two enzymes for one substrate. The assay was used on two
      ribozymes, hammerhead ribozyme and hairpin ribozyme, and a DNA-enzyme. We found
      that this assay method is capable of application to those enzymes, as a powerful
      tool for the selection and designing of RNA-cleaving enzymes.

PMID- 11515550
TI  - Inhibition by Agaricus blazei Murill fractions of cytopathic effect induced by
      western equine encephalitis (WEE) virus on VERO cells in vitro.
AB  - Anti-viral activities of Agaricus blazei Murill were investigated. The water
      extracts of the cultured mycelia and fruiting bodies were fractionated with
      different concentrations of ethanol. To several viruses which have cytopathic
      effects (CPE) on VERO cells, inhibition of these effects by the ethanol fractions
      was tested. Strong inhibition of CPE induced by western equine encephalitis (WEE)
      virus was observed in the mycelial fractions but not those of fruiting bodies.

PMID- 11515551
TI  - Purification of saponin compounds in Bupleurum falcatum by solvent partitioning
      and preparative LC.
AB  - Saponin compounds (saikosaponin c, a, and d) in Bupleurum falcatum were partially
      purified by solvent partitioning of the herbal extract using diethyl ether,
      distilled water, n-butanol, and acetone. After separation of the saponins by
      preparative LC, the purity of each saikosaponin was more than 94%. The identities
      of purified individual saikosaponins were confirmed by TLC, analytical LC, and
      fast-atom bombardment mass spectrometry.

PMID- 11515553
TI  - Acetyl-CoA carboxylase inhibitors from avocado (Persea americana Mill) fruits.
AB  - A methanol extract of avocado fruits showed potent inhibitory activity against
      acetyl-CoA carboxylase, a key enzyme in fatty acid biosynthesis. The active
      principles were isolated and identified as (5E,12Z,15Z)-2-hydroxy-4-oxoheneicosa
      5,12,15-trienyl (1), (2R,12Z,15Z)-2-hydroxy-4-oxoheneicosa-12,15-dienyl (2),
      (2R*,4R*)-2,4-dihydroxyheptadec-16-enyl (3) and (2R*,4R*)-2,4-dihydroxyheptadec
      16-ynyl (4) acetates by instrumental analyses. The IC50 of the compounds were 4.0
      x 10(-6), 4.9 x 10(-6), 9.4 x 10(-6), and 5.1 x 10(-6) M, respectively.

PMID- 11515552
TI  - Antimutagenicity of deacylated anthocyanins in purple-fleshed sweetpotato.
AB  - The antimutagenicity of the 3-sophoroside-5-glucoside of cyanidin and 3
      sophoroside-5-glucoside of peonidin, the anthocyanin derivatives deacylated from
      the 3-(6,6'-caffeylferulylsophoroside)-5-glucoside of cyanidin (YGM-3) and 3
      (6,6'-caffeylferulylsophoroside)-5-glucoside of peonidin (YGM-6) which had been
      purified from the sweetpotato with purple-colored flesh, was investigated by
      using Salmonella typhimurium TA 98. A comparison of the antimutagenicity between
      YGM-3 and YGM-6 and the deacylated derivatives showed that the activity of
      cyanidin was stronger than that of peonidin. Deacylation of the peonidin-type
      pigment markedly decreased this antimutagenicity. Caffeic acid showed the
      strongest antimutagenicity of the constituent organic acids of the anthocyanin
      pigments, caffeic acid, ferulic acid, and p-hydroxybenzoic acid. These results
      suggest that the cathecol structure plays an important role in the strong
      antimutagenicity of anthocyanin pigments.

PMID- 11515554
TI  - Purification and properties of two malate dehydrogenases from Candida sp. N-16
      grown on methanol.
AB  - Two malate dehydrogenases (MDH-M1 and MDH-M2) were found in a methanol-using
      yeast, Candida sp. N-16. MDH-M2 was induced with methanol. These enzymes were
      purified as electrophoretically and isoelectrophoretically homogeneous proteins.
      The molecular weights of MDH-M1 and MDH-M2 were estimated to be about 78,000
      (homodimer) and 160,000 (homotetramer). Several kinetic properties were
      significantly different between the two enzymes. The value (2.07) of
      Vmax(oxaloacetate)/Vmax(malate) and Kcats (555 s(-1) for oxaloacetate, 481 s(-1)
      for NADH) of MDH-M2 were higher than the ratio (1.37) of Vmax and Kcats (241 s(
      1) for oxaloacetate, 271 s(-1) for NADH) of MDH-M1, respectively. The activity of
      MDH-M2 was inhibited by a high concentration of NAD+ and the activity of MDH-M1
      by oxaloacetate.

PMID- 11515555
TI  - A basic class I chitinase expression in winged bean is up-regulated by osmotic
      stress.
AB  - We isolated a cDNA for basic class I chitinase (ChitiWb1). ChitiWb1 cDNA encodes
      a protein that consists of 315 amino acid residues and has a signal peptide.
      Northern blot analysis indicated that the class I chitinase mRNA in leaves and
      cultured cells of winged bean was increased by treatments with NaCl, KCl, CaCl2,
      mannitol or saccharose, but not with abscisic acid. Thus, class I chitinase
      expression was shown to be up-regulated by osmotic stress.

PMID- 11515556
TI  - Synthesis of cis-lactone lignan, cis-(2S,3R)-parabenzlactone, from L-arabinose.
AB  - As a model synthesis on cis-2,3-dibenzyl-4-butanolide lignan, cis-(2S,3R)
      parabenzlactone bearing a chiral benzyl alcohol moiety was stereoselectively
      synthesized from L-arabinose.

PMID- 11515557
TI  - Anti-inflammatory and anti-allergic actions by oral administration of a perilla
      leaf extract in mice.
AB  - The anti-inflammatory and anti-allergic activity of perilla leaf extract was
      investigated. The oral administration of perilla leaf extract to mice inhibited
      two types of acute inflammatory models, arachidonic acid-induced ear edema and 12
      o-tetradecanoylphorbol-13-acetate-induced ear edema. Oral administration of
      perilla leaf extract also inhibited the contact dermatitis model, oxazolone
      induced ear edema, by affecting sensitization.

PMID- 11515558
TI  - Stereoselective reduction of ethyl 4-chloro-3-oxobutanoate by fungi.
AB  - The enantioselectivity of ECAA to ECHB by eight fungi of four genus was
      evaluated. All strains showed (S)-selectivity, and Cylindrocarpon sclerotigenum
      IFO 31855 gave the highest yield and good optical purity (e.e.; >99%). Cell-free
      extract and acetone-dried cells of C. sclerotigenum IFO 31855 reduced ECAA to (S)
      ECHB in the presence of NADPH (e.e.; >99%) and the e.e. was not decreased by heat
      treatment of the cell-free extract or the acetone-dried cells. The active
      fractions shown by two peaks on a DEAE-Toyopearl 650 M column gave preferentially
      (S)-ECHB (e.e.; >99%).

PMID- 11515559
TI  - Purification and characterization of an esterase from Micrococcus sp. YGJ1
      hydrolyzing phthalate esters.
AB  - An esterase hydrolyzing phthalate esters has been purified from Micrococcus sp.
      YGJ1. The enzyme, a monomeric protein (Mr = 56 kDa) with a pI of 4.0, hydrolyzes
      various aliphatic and aromatic carboxylesters. The medium chain (C3-C4) esters
      are the most preferred substrates. The enzyme is inhibited by HgCl2 and p
      chloromercuribenzoate but not by phenylmethylsulfonyl fluoride.

PMID- 11515560
TI  - Cloning and nucleotide sequence of the mycodextranase gene from Streptomyces sp.
      J-13-3.
AB  - Mycodextranase (EC 3.2.1.61) is an alpha-glucanase that cleaves alpha-1,4-bonds
      of alternating alpha-1,3- and alpha-1,4-linked D-glucan (nigeran). The gene
      encoding mycodextranase from Streptomyces sp. J-13-3 was cloned by hybridization
      with a degenerate oligonucleotide probe from the amino-terminal amino acid
      sequence of the enzyme and its nucleotide structure was analyzed. The open
      reading frame consisted of 1,803 base pairs encoding a signal peptide of 60 amino
      acids and a mature protein of 540 amino acids with a calculated molecular weight
      of 56,078. The deduced amino acid sequence showed weak similality to a chitinase
      homolog from Streptomyces lividans and a chitinase from Xanthomonas sp.

PMID- 11515561
TI  - Introduction of bacterial metabolism into higher plants by polycistronic
      transgene expression.
AB  - Multiple-gene transformation is required to improve or change plant metabolisms
      effectively; but this many-step procedure is time-consuming and costing. We
      succeeded in the metabolic engineering of tobacco plants by introducing multiple
      genes as a bacteria-type operon into a plastid genome. The tobacco plastid was
      transformed with a polycistron consisting of three bacterial genes for the
      biosynthesis of a biodegradable polyester, polyhydroxybutyrate (PHB).
      Accumulation of PHB in the leaves of the transgenic tobacco indicated that the
      introduced genes were polycistronically expressed. This "phyto-fermentation"
      system can be used in plant production of various chemical commodities and
      pharmaceuticals.

PMID- 11515562
TI  - The expression of a barley HvNAS1 nicotianamine synthase gene promoter-gus fusion
      gene in transgenic tobacco is induced by Fe-deficiency in roots.
AB  - Nicotianamine (NA) is a precursor for mugineic acid-family phytosiderophores,
      which are a critical component of the Fe aquisition process in graminaceous
      plants. In addition, nicotianamine synthase (NAS) is strongly induced in these
      plants by Fe deficiency. NA is essential for Fe metabolism also in dicots, but
      NAS is not induced by Fe deficiency. We introduced a barley HvNAS1 promoter-gus
      fusion gene into tobacco. GUS activity was induced in the roots of these plants
      by Fe deficiency, and was constitutively expressed at a low level in their
      leaves.

PMID- 11515563
TI  - Origins and consequences of age at first drink. II. Familial risk and
      heritability.
AB  - BACKGROUND: The association of age at first drink (AFD) and alcoholism may
      reflect a common inherited vulnerability to disinhibitory behavior and
      psychopathology rather than a direct influence of the former on the latter. We
      tested the common-inherited-vulnerability hypothesis by determining whether AFD
      is familial and heritable. METHODS: A sample of 1,232 14-year-old twins was
      classified according to their biological parents' AFD. RESULTS: Lifetime symptoms
      of externalizing disorders (i.e., conduct disorder and oppositional defiant
      disorder) were significantly higher in the sons but not the daughters of parents
      whose AFD came before age 15 years. Offspring symptoms of internalizing disorders
      (i.e., major depressive disorder, separation anxiety disorder, and overanxious
      disorder) were not significantly associated with parental early use of alcohol in
      either sons or daughters. Early use of alcohol in mothers but not fathers was
      associated with a significant increase in both sons' and daughters' risk of
      alcohol use by age 14. The contribution of genetic and environmental factors to
      risk of early alcohol use was investigated in a sample of 416 monozygotic (MZ)
      and 225 like-sex dizygotic (DZ) 14-year-old twin pairs. Twin similarity for early
      alcohol use was substantially greater in MZ than DZ twins in boys but about
      equally similar in MZ and DZ twins in girls. Estimated heritability of early
      alcohol use was significantly greater in boys (55%) than girls (11%), in part
      because the genetic factors underlying symptoms of disinhibitory psychopathology
      contributed more to risk of early alcohol use in boys than girls. CONCLUSIONS:
      Early use of alcohol is familial and, at least in males, heritable. The familial
      transmission of early alcohol use is caused in part by genetic risk for
      disinhibitory psychopathology in males and to shared environmental factors in
      girls. These results provide some support for a common-inherited-vulnerability
      hypothesis, and suggest that the processes underlying early alcohol use may
      differ in boys and girls.

PMID- 11515564
TI  - There's no need to risk retinal light toxicity in the medical management of
      progressive school myopia with atropine (and photochromic bifocals). It is
      medically indicated.

PMID- 11515565
TI  - Report of the meeting of the American Academy of Pediatrics Section on
      Ophthalmology. "Why Can't EYE Learn?'.

PMID- 11515566
TI  - Tennessee Dental Association membership directory, 2001-2002.

PMID- 11515567
TI  - XVth National Meeting of the Argentine Society for Neurochemistry. Complejo
      Vaquerias, Cordoba, Argentina. November 23-26, 2000. Abstracts.

PMID- 11515568
TI  - Medicinal foodstuffs. XXV. Hepatoprotective principle and structures of ionone
      glucoside, phenethyl glycoside, and flavonol oligoglycosides from young seedpods
      of garden peas, Pisum sativum L.
AB  - A new ionone glucoside, pisumionoside, a phenethyl glycoside, sayaendoside, and
      two acylated flavonol oligoglycosides, pisumflavonosides I and II, were isolated
      from the young seedpods of garden peas, Pisum sativum L., together with quercetin
      and kaempferol 3-O-(6-O-trans-p-coumaroyl)-beta-D-glucopyranosyl (1-->2)-beta-D
      glucopyranosyl (1-->2)-beta-D-glucopyranosides and quercetin and kaempferol 3
      sophorotriosides. The structures of pisumionoside, sayaendoside, and
      pisumflavonosides I and II were determined on the basis of chemical and
      physicochemical evidence, respectively. Quercetin 3-sophorotrioside, a principle
      component, was found to show protective effects on liver injury induced by D
      galactosamine and lipopolysaccharide and by carbon tetrachloride in mice.

PMID- 11515569
TI  - Synthesis and structure-activity relationship of N-arylrolipram derivatives as
      inhibitors of PDE4 isozymes.
AB  - Structure activity studies of N-phenylrolipram derivatives have led to the
      identification of highly potent PDE4 inhibitors. The potential of these
      inhibitors for cellular activity was routinely assessed in an assay of fMLP
      induced oxidative burst in human eosinophils. Since first generation PDE4
      inhibitors have been plagued with a number of unwanted side effects, parallel
      structure activity studies for competition with the [3H]-rolipram binding site in
      rat brain were performed. In this fashion 5-[4-(3-cyclopentyloxy-4-methoxyphenyl)
      2-oxo-pyrrolidin-1-yl]-3-(3-methoxybenzyloxy)benzoic acid N',N'-dimethylhydrazide
      (22) was identified as a potent inhibitor of PDE4 which exhibits >1000 fold
      selectivity versus PDE3, and is a nanomolar inhibitor in all the cellular assays
      tested. Studies on the stereoselectivity of PDE4 inhibition of this class of
      rolipram based compounds revealed, that for example (S)-11 is a more potent
      inhibitor than (R)-11. This effect can also be observed in primary human cells
      where the (S)-enantiomer is about 10 fold more potent than the corresponding (R)
      enantiomer.

PMID- 11515570
TI  - The practical synthesis of a uterine relaxant, bis(2-[[(2S)-2-([(2R)-2-hydroxy-2
      [4-hydroxy-3-(2-hydroxyethyl)-phenyl]ethyl]amino)-1,2,3,4-tetrahydronaphthalen-7
      yl]oxy]-N,N-dimethylacetamide) sulfate (KUR-1246).
AB  - The synthetic route for a uterine relaxant, bis(2-[[(2S)-2-([(2R)-2-hydroxy-2-[4
      hydroxy-3-(2-hydroxyethyl)-phenyl]ethyl]amino)-1,2,3,4-tetrahydronaphthalen-7
      yl]oxy]-N,N-dimethylacetamide) sulfate (KUR-1246), was established by the
      coupling of optically active components, the bromohydrin 14 and the amine 24. We
      now describe the practical synthesis of these two optically active components.
      Bromohydrin 14 was obtained by the asymmetric borane reduction of the prochiral
      phenacyl bromide 13 using a catalyst prepared from aluminum triethoxide and a
      chiral amino alcohol. The other optically active component 24 was prepared from
      (S)-AMT.

PMID- 11515571
TI  - Semialactone, isofouquierone peroxide and fouquierone, three new dammarane
      triterpenes from Rhus javanica.
AB  - Three new dammarane triterpenes and semialactic acid were isolated from the stem
      bark of Rhus javanica. The structures of these triterpenes, named semialactone,
      isofouquierone peroxide and fouquierone, were elucidated by 2D-NMR analysis
      (HMQC, 1H-1H COSY and HMBC), and the 13C-NMR data of semialatic acid is revised.

PMID- 11515572
TI  - Fmoc-POAC: [(9-fluorenylmethyloxycarbonyl)-2,2,5,5-tetramethylpyrrolidine-N-oxyl
      3-amino-4-carboxylic acid]: a novel protected spin labeled beta-amino acid for
      peptide and protein chemistry.
AB  - The stable free radical 2,2,6,6-tetramethylpiperidine-N-oxyl-4-amino-4-carboxylic
      acid (TOAC) is the only spin labeled amino acid that has been used to date to
      successfully label peptide sequences for structural studies. However, severe
      difficulty in coupling the subsequent amino acid has been the most serious
      shortcoming of this paramagnetic marker. This problem stems from the low
      nucleophilicity of TOAC's amine group towards the acylation reaction during
      peptide chain elongation. The present report introduces the alternative beta
      amino acid 2,2,5,5-tetramethylpyrrolidine-N-oxyl-3-amino-4-carboxylic acid
      (POAC), potentially useful in peptide and protein chemistry. Investigations aimed
      at addressing the stereochemistry of this cyclic molecule through X-ray
      diffraction measurements of crystalline and bulk samples revealed that it
      consists only of the trans conformer. The 9-fluorenylmethyloxycarbonyl group
      (Fmoc) was chosen for temporary protection of the POAC amine function, allowing
      insertion of the probe at any position in a peptide sequence. The vasoactive
      octapeptide angiotensin II (All, DRVYIHPF) was synthesized by replacing Pro7 with
      POAC. The reaction of Fmoc-POAC with the peptidyl-resin occurred smoothly, and
      the coupling of the subsequent amino acid showed a much faster reaction when
      compared with TOAC. POAC7-AII was obtained in good yield, demonstrating that, in
      addition to TOAC, POAC is a convenient amino acid for the synthesis of spin
      labeled peptide analogues. The present findings open the possibility of a wide
      range of chemical and biological applications for this novel beta-amino acid
      derivative, including structural investigations involving its differentiated bend
      inducing characteristics.

PMID- 11515573
TI  - Two new steroidal derivatives from the fruit body of Chlorophyllum molybdites.
AB  - Two new steroid derivatives, (22E,24R)-3alpha-ureido-ergosta-4,6,8(14),22
      tetraene (1) and (22E,24R)-5alpha,8alpha-epidioxyergosta-6,9,22-triene-3beta-ol 3
      O-beta-D-glucopyranoside (2) were isolated from the fruit bodies of Chlorophyllum
      molybdites (Agaricaceae). The structures were established by spectroscopic and
      chemical methods. These compounds exhibited cytotoxicity against Kato III cells.

PMID- 11515574
TI  - Quinone-type podocarpanes from the bark of Taiwania cryptomerioides.
AB  - Three quinone-type podocarpanes, 3beta-hydroxy-13-methoxy-8,12-podocarpadiene
      11,14-dione (1), 18-hydroxy-13-methoxy-8,12-podocarpadiene-11,14-dione (2), and
      13-methoxy-8,12-podocarpadiene-2,11,14-trione (3) were isolated from the bark of
      Taiwania cryptomerioides. Their structures were elucidated using spectral
      methods.

PMID- 11515575
TI  - Studies on a medicinal parasitic plant: lignans from the stems of Cynomorium
      songaricum.
AB  - Eight phenolic compounds including two new lignan glucopyranosides together with
      a known alkaloid were isolated from the stems of Cynomorium songaricum RUPR.
      (Cynomoriaceae). Their chemical structures were elucidated on the basis of
      spectral and chemical evidence. The chemotaxonomic significance of these
      metabolites is discussed.

PMID- 11515576
TI  - Phlomisflavosides A and B, new flavonol bisglycosides from Phlomis spinidens.
AB  - From the aerial parts of Phlomis spinidens, two new flavonol bisglycosides,
      phlomisflavosides A (1) and B (2), were isolated together with the known
      compounds, astragalin, isoquercitrin, lamiridoside, phlomoside A, shanzhiside
      methyl ester, 8-O-acetylshanzhiside methyl ester, phlorigidoside C, rodioloside
      (=salidroside), forsythoside B, citroside A and lariciresinol-4'-O-beta-D
      glucoside. The structures of the new compounds were elucidated based on spectral
      and chemical evidence.

PMID- 11515577
TI  - Cholestane glycosides from the bulbs of Galtonia candicans and their
      cytotoxicity.
AB  - Further search for cytotoxic compounds contained in the bulbs of Galtonia
      candicans (Liliaceae) led to the isolation of four potent cytotoxic cholestane
      glycosides (1-4) based upon 3beta,16beta,17alpha-trihydroxycholest-5-en-22-one,
      three of which (2-4) have not been reported previously. A new cholestane
      bisdesmoside (5) and a new rearranged cholestane glycoside (6) were also
      isolated. The structural assignment of the new constituents was carried out by
      spectroscopic analysis and a few chemical transformations.

PMID- 11515578
TI  - Protease-catalyzed monoacylation of 2-O-alpha-D-Glucopyranosyl-L-ascorbic acid in
      pyridine.
AB  - 2-O-alpha-D-Glucopyranosyl-6-O-octanoyl-L-ascorbic acid was enzymatically
      synthesized from 2-O-alpha-D-glucopyranosyl-L-ascorbic acid (AA-2G) and vinyl
      octanoate with a protease from Bacillus subtilis in pyridine. Furthermore, with
      various linear saturated fatty acid vinylesters as acyl donors, AA-2G was also
      converted to their corresponding 6-O-acyl AA-2G in the same manner. The
      reactivities of transacylation decreased with increasing length of the acyl
      groups. Thus, short chain acyl groups were transferred to AA-2G by this protease
      more efficiently than were long chain acyl groups. This enzymatic method is
      recommended for the synthesis of 6-Acyl-AA-2G with short or medium length chain
      acyl groups.

PMID- 11515579
TI  - Possible remediation of dioxin-polluted soil by steam distillation.
AB  - 2,7-Dichlorodibenzo-p-dioxin (DCDD) was found to evaporate easily with water
      vapor from a heated solution. Steam distillation was also effective for the
      removal of DCDD from DCDD-applied soil; its concentration (250 microg/50g soil)
      in the original soil decreased to less than 5% after steam distillation for only
      20 min. Actual dioxin-polluted soil in Tokorozawa City was partially
      decontaminated using the same method. These results suggest that steam
      distillation could be a new remedial method for soils contaminated with
      persistent environmental pollutants, such as dioxins and polychlorinated
      biphenyls.

PMID- 11515580
TI  - "One-pot" synthesis and antimalarial activity of formamidine derivatives of 4
      anilinoquinoline.
AB  - Amodiaquine (AQ) is an antimalarial which is effective against chloroquino
      resistant strains of Plasmodium falciparum but whose clinical use is severely
      restricted because of associated hepatotoxicity and agranulocytosis. "One-pot"
      synthesis of formamidines likely to be transformed into AQ derivatives is
      reported. Compared with AQ, the new compounds were devoid of in vitro
      cytotoxicity upon human embryonic lung cells and mouse peritoneal macrophages.
      One showed a potent in vivo activity in mice infected with P berghei.
      Transformation of this compound by reductive amination led to a new type of AQ
      derivatives that displayed an in vitro activity similar to that of AQ but did not
      lead to toxic quinone-imines.

PMID- 11515582
TI  - Antioxidative properties of probucol estimated by the reactivity with superoxide
      and by electrochemical oxidation.
AB  - The reaction of probucol with superoxide (O2(*-)) was investigated in
      acetonitrile using both electron spin resonance (ESR) and electrochemical
      techniques. The formation of phenoxyl radical was observed during the reaction of
      probucol with O2(*-) by ESR spectroscopy. The reaction of probucol with O2(*-) in
      acetonitrile was followed by cyclic voltammetry. With the addition of probucol,
      the oxidation peak current of O2(*-) decreased concentration dependently. This
      suggests that probucol reacts with O2(*-), that is, probucol scavenges O2(*-) in
      acetonitrile. 2,6-Di-tert-butyl-p-benzoquinone was identified as the major
      product of the reaction of probucol with O2(*-) in acetonitrile. Electrochemical
      oxidation of probucol was also performed. Probucol gives an irreversible
      oxidation peak at ca. +1.4 V vs. the saturated calomel electrode in the cyclic
      voltammogram. Controlled-potential electrolysis was carried out at +1.2 V in a
      divided cell. 2,6-Di-tert-butyl-p-benzoquinone, 4,4'-dithiobis(2,6-di-tert
      butylphenol), and 4,4'-trithiobis(2,6-di-tert-butylphenol) were identified as the
      products of anodic oxidation. These redox properties of probucol may correlate
      with the physiological activities.

PMID- 11515581
TI  - Antiallergic agents from natural sources. 3. Structures and inhibitory effects on
      nitric oxide production and histamine release of five novel polyacetylene
      glucosides from Bidens parviflora WILLD.
AB  - Five new polyacetylene glucosides, bidensyneosides A1, A2, B, C (1-4), and 3
      deoxybidensyneoside B (5), have been isolated from the air-dried whole plant of
      Bidens parviflora WILLD. The structures were identified based on spectroscopic
      analysis, physicochemical properties, and application of the modified Mosher
      method to be 3(R),8(E)-8-decene-4,6-diyne-1,3-diol 1-O-beta-D-glucopyranoside
      (1), deca-3(R),8(Z) 8-decene-4,6-diyne-1,3-diol 1-O-beta-D-glucopyranoside (2),
      3(R)-deca-4,6,8-triyne-1,3-diol 1-O-beta-D-glucopyranoside (3), 3(R),8(E)-8
      decene-4,6-diyne-1,3,10-triol 1-O-beta-D-glucopyranoside (4), and 8(E)-8-decene
      4,6-diyne-1,10-diol 1-O-beta-D-glucopyranoside (5), respectively. These compounds
      inhibited nitric oxide (NO) production in lipopolysaccharide and interferon-gamma
      activated murine macrophages (RAW264.7) and also inhibited histamine release from
      rat mast cells stimulated by the antigen-antibody reaction.

PMID- 11515583
TI  - Synthesis and physiological activity of novel tocopheryl glycosides.
AB  - Vitamin E glycosides were synthesized and enzymatic hydrolysis was examined for
      use as potential pro-drugs, however, the glycoside bond was found to be stable.
      On the other hand, among the glycosides synthesized, dl-alpha-tocopherylglucoside
      (6b) and dl-alpha-tocopherylmannoside (6c) showed strong inhibitory action on
      histamine release from mast cells. In addition, 6c also showed a suppressive
      action on IgE antibody formation. Thus, tocopheryl glycoside showed new
      properties compared to tocopherol (vitamin E). In particular, 6c was shown to be
      a novel lead compound with excellent manifold anti-allergic activity and anti
      inflammatory activity.

PMID- 11515584
TI  - Anti-androgenic triterpenoids from the Brazilian medicinal plant, Cordia
      multispicata.
AB  - Compounds 1-6 were isolated from the AcOEt soluble fraction of leaves of the
      Brazilian medicinal plant, Cordia multispicata, and their structures were
      elucidated to be 3beta,25-epoxy-21beta-acetoxy-3alpha,22beta-dihydroxyurs-12-en
      28-al (1), 3beta,25-epoxy-28-acetoxy-3alpha,21beta,22beta-trihydroxyurs-12-ene
      (2), 21beta-acetoxy-22beta-hydroxy-3-oxours-12-en-28-al (3), 28-acetoxy-6beta,
      21beta,22beta-trihydroxy-3-oxours-12-ene (4), 21beta,22beta-dihydroxy-3-oxours-1
      2-en-28-al (5) and 3beta,21beta,22beta-trihydroxyurs-I2-en-28-al (6),
      respectively, by means of spectral data, especially two dimensional NMR
      techniques. Triterpenes having the hemiketal structure at the A-ring, an acyloxy
      group at C-22 and/or ketone at C-3 showed potent anti-androgenic activity.

PMID- 11515585
TI  - Facile solid-phase synthesis of sulfated tyrosine-containing peptides: Part II.
      Total synthesis of human big gastrin-II and its C-terminal glycine-extended
      peptide (G34-Gly sulfate) by the solid-phase segment condensation approach.
AB  - Application of the fluoren-9-ylmethoxycarbonyl (Fmoc)-based solid-phase segment
      condensation approach to the preparation of sulfated peptides was investigated
      through the synthesis of human big gastrin-II, a 34-residue sulfated tyrosine
      [Tyr(SO3H)]-containing peptide. Highly acid-sensitive 2-chlorotrityl resin (Clt
      resin) was exclusively employed as an anchor-resin for the preparation of the
      three peptide segments having the C-terminal Pro residue as well as of the
      Tyr(SO3H)-containing resin-bound segment. By using the PyBOP-mediated coupling
      protocol [PyBOP=benzotriazolyloxytris(pyrrolidino)phosphonium
      hexafluorophosphatel, we successively condensed each segment and constructed the
      34-residue peptide-resin without any difficulty. The final acid treatment of the
      fully protected peptide-resin at low temperature (90% aqueous TFA, 0 degree C for
      8 h), which can detach a Tyr(SO3H)-containing peptide from the resin and remove
      the protecting groups concurrently with minimum deterioration of the sulfate,
      afforded a crude sulfated peptide. After one-step HPLC purification, a highly
      homogeneous human big gastrin-II was easily obtained in 14% yield from the
      protected peptide-resin. The sulfate form of the C-terminal glycine-extended
      gastrin (G34-Gly sulfate), a posttranslational processing intermediate of gastrin
      II, was also successfully prepared with the segment condensation approach (11%
      yield). These results demonstrated the usefulness of the segment condensation
      protocol for preparing large Tyr(SO3H)-containing peptides.

PMID- 11515586
TI  - Intercalation compounds of layered materials for drug delivery use. II.
      Diclofenac sodium.
AB  - Intercalation compounds of ternary layered inorganic materials, synthetic mica
      (Na-TSM), with diclofenac sodium (DFS) and its drug release characteristics were
      investigated. Hygroscopic DFS was selected as a model drug to verify the anti
      humidity and anti-oxidation of the intercalation compounds. Na-TSM powder was
      first mixed with the reduced-type phosphatidylcholine (H-PC) solution of
      chloroform or ethanol. DFS was then mixed with these solutions and heated at 37
      degrees C to prepare the ternary Na-TSM/H-PC/DFS compound. A remarkable
      phenomenon was observed in the drug release study. The net amount of DFS from the
      DFS powder decreased apparently after 20 min arising from the decomposition of
      DFS in acidic medium. On the other hand, the net amount of the released DFS from
      the intercalation compound was invariant. Thermal analyses study indicated that
      DFS powder was hygroscopic and a significant endothermic peak was observed
      accompanied by a large weight loss due to the dehydration of adsorbed water from
      40 to 90 degrees C. On the other hand, no significant dehydration reaction was
      observed in the intercalation compounds even in the sample stored under humid
      conditions. The present results indicated that the ternary intercalation compound
      was resistant to acid in addition to anti-humidity.

PMID- 11515587
TI  - Studies on anthracenes. 1. Human telomerase inhibition and lipid peroxidation of
      9-acyloxy 1,5-dichloroanthracene derivatives.
AB  - The synthetically useful approaches to 9-acyloxy 1,5-dichloroanthracene
      derivatives are reported. The system selectively reduces the carbonyl group
      flanked by the peri substituents of the anthracenediones to give the
      corresponding 1,5-dichloro-9(10H)-anthracenone. Simple regioselective acylation
      of anthracenone is applied with appropriate acyl chlorides in CH2Cl2 with
      catalytic amount of pyridine to give the novel 9-acyloxy 1,5-dichloroanthracene
      derivatives. Considerable interest has developed in the mechanism of how
      anthracenone achieves this desirable selectivity. In an attempt to understand the
      mechanism of this reaction, solid-state structures of anthracene derivatives have
      been obtained. In addition, the inhibition of lipid peroxidation in model
      membranes was determined as was their ability to inhibit the telomere-addition
      function of the human telomerase enzyme together with their inhibition of the Taq
      polymerase enzyme. In contrast to (+)-alpha-tocopherol, 3b, 3c, 3d, 3g, and 3i do
      not enhance lipid peroxidation in model membranes. Implications for 9-acyloxy 1,5
      dichloroanthracene analogues as potential anticancer agents are discussed.

PMID- 11515588
TI  - Medicinal flowers. IV. Marigold. (2): Structures of new ionone and sesquiterpene
      glycosides from Egyptian Calendula officinalis.
AB  - Following the characterization of hypoglycemic, gastric emptying inhibitory, and
      gastroprotective principles and the structure elucidation of calendasaponins A,
      B, C, and D, two new ionone glucosides (officinosides A and B), and two
      sesquiterpene oligoglycosides (officinosides C and D), were isolated from the
      flowers of Egyptian Calendula officinalis. The structures of the officinosides
      were elucidated on the basis of chemical and physicochemical evidence.

PMID- 11515589
TI  - A synthesis of 3-phenyl-1,2,3,4-tetrahydroisoquinoline and 2-phenyl-1,2,4,5
      tetrahydro-3H-3-benzazepine via Pummerer-type cyclization: enhancing effect of
      boron trifluoride diethyl etherate on the cyclization.
AB  - A synthesis of 6,7-dimethoxy-3-phenyl-1,2,3,4-tetrahydroisoquinoline (14a) and
      7,8-dimethoxy-2-phenyl-1,2,4,5-tetrahydro-3H-3-benzazepine (14b) was achieved via
      the cyclization of N-(3,4-dimethoxyphenyl)methyl-1-phenyl-2
      (phenylsulfinyl)ethylformamide (6a) and N-2-(3,4-dimethoxyphenyl)ethyl-1-phenyl-2
      (phenylsulfinyl)-ethylformamide (6b) using the Pummerer reaction as a key step,
      respectively. The Pummerer reaction of 6a,b under usual conditions using
      trifluoroacetic anhydride yielded the vinyl sulfides (8a, b), non-cyclized
      products, as a major product. The cyclization proceeded when boron trifluoride
      diethyl etherate was used as an additive reagent, thus giving rise to the
      corresponding cyclized products (7a) and (7b) in moderate yields. We propose that
      the enhancing effect of the Lewis acid on the cyclization may be attributable to
      the involvement of a dicationic intermediate, sulfonium-carbenium dication (23).

PMID- 11515590
TI  - Structure of three new carotenoids with a 3-methoxy-5-keto-5,6-seco-4,6-cyclo
      beta end group from the seeds of Pittosporum tobira.
AB  - Three new carotenoids with a 3-methoxy-5-keto-5,6-seco-4,6-cyclo-beta end group
      (1-3) have been isolated from the seeds of Pittosporum tobira. Their structures
      were elucidated by detailed analyses of nuclear magnetic resonance and UV data.

PMID- 11515591
TI  - Design, synthesis and biological evaluation of a novel series of potent, orally
      active adenosine A1 receptor antagonists with high blood-brain barrier
      permeability.
AB  - A novel series of 3-(2-substituted-3-oxo-2,3-dihydropyridazin-6-yl)-2
      phenylpyrazolo[1,5-a]pyridines (5-38) were synthesized and evaluated for their in
      vitro adenosine A1 and A(2A) receptor binding activities, and in vitro metabolism
      by rat liver in order to search for orally active compounds. Most of the test
      compounds were potent adenosine A1 receptor antagonists with high A1 selectivity
      and the A1 affinity and A1 selectivity of carbonyl derivatives (5-11) was
      particularly high. In particular, compound 7 was an extremely potent and
      selective adenosine A1 antagonist with high A1 selectivity (Ki=0.026 nM,
      A(2A)/A1=5400). In terms of metabolic stability, 2-oxopropyl (5), 2-hydroxypropyl
      (12), N-methylacetamide (16), 2-(piperidin-1-yl)ethyl (28) and 1-methylpiperidin
      4-yl (32, FR194921) were the most stable compounds in this series of analogues.
      Further in vivo evaluation indicated that compounds 5, 13, 17, 28 and 32 were
      detected in both plasma and brain after oral administration in rats. In
      particular, 32 displayed good plasma and brain concentrations (dose: 32 mg/kg
      (n=3); after 30 min, plasma conc.=3390+/-651nM, brain conc.=3670+/-496nM; after
      60min, plasma conc.=1580+/-348nM, brain conc.=2143+/-434nM), and a good
      brain/plasma ratio (1.11+/-0.060 (30min), 1.39+/-0.172 (60min)). As a result, we
      could show that 32 is a good candidate for an orally active adenosine A1 receptor
      antagonist with high blood-brain barrier permeability and good bioavailability
      (Ki=6.6nM, A(2A)/A1=820, BA=60.6+/-4.9% (32 mg/kg)).

PMID- 11515592
TI  - Fargosides A-E, triterpenoid saponins from Holboellia fargesii.
AB  - Five new triterpenoid saponins, fargosides A, B, C, D, and E, were isolated from
      the roots of Holboellia fargesii. The structures of fargosides A-E were
      elucidated on the basis of chemical and physicochemical evidence and found to be
      3beta,20alpha-dihydroxy-29-norolean-12-en-28-oic acid 3-O-beta-D-xylopyranosyl-(1
      ->2)-beta-D-glucopyranoside (1), 3beta,20alpha,24-trihydroxy-29-norolean-12-en-28
      oic acid 23-O-beta-D-fucopyranosyl-(1-->2)-[alpha-L-arabinopyranosyl-(1-->3)]
      beta-D-glucopyranoside (2), 3beta,23-dihydroxy-30-norolean-2,20(29)-dien-28-oic
      acid 3-O-alpha-L-arabinopyranosyl-(1-->2)-[beta-D-glucopyranosyluronic acid-(1-
      >3)]-alpha-L-arabinopyranoside (3), 3beta,23-dihydroxy-30-norolean-12,20(29)-dien
      28-oic acid 3-O-methyl beta-D-glucopyranosyluronate-(1-->3)-alpha-L
      arabinopyranoside (4), and 3beta,23-dihydroxy-olean-12-en-28-oic acid 3-O-methyl
      beta-D-glucopyranosyluronate-(1-->3)-alpha-L-arabinopyranoside (5), respectively.

PMID- 11515593
TI  - Reinforcement of maxillary dentures with silane-treated ultra high modulus
      polyethylene fibers.
AB  - Midline fractures appear to be the most common problem in maxillary complete
      dentures, and they can be prevented by reinforcement of the base material. In
      this clinical trial, complete upper dentures made, for patients having a history
      of midline fractures, that were reinforced with ultra-high modulus polyethylene
      fiber in woven form. This fiber was treated with a silane-coupling agent and
      sandwiched between acrylic dough. Laboratory procedures were conducted easily and
      conventionally, without any special equipment. At the end of 18 months, all of
      the dentures were well accepted and did not show any signs of fracture.

PMID- 11515594
TI  - Possible participation of isolated epicardial cell clusters in the formation of
      chick embryonic epicardium.
AB  - The embryonic epicardium is formed by the spreading of cells derived from the
      extracardiac proepicardial organ over the myocardial surface after transfer to
      the dorsal side of the myocardium via a bridge of villous projections. Using
      whole-heart immunostaining for keratin, we found that the chronology and pattern
      of epicardial formation in the chick was basically identical to that reported
      previously in the quail. However, discrete epicardial islands were observed on
      the ventrolateral surface of the atrioventricular canal as well as in two
      previously reported areas. Closer examination by scanning electron microscopy
      demonstrated the presence of isolated, sparsely distributed epicardial cell
      clusters on both the dorsal and ventral surfaces of the myocardium. These cells
      showed a surface morphology similar to that of the epicardial cells at the
      advancing edge of the spreading epicardial sheet and possessed numerous well
      developed filopodia, suggesting active motility. These clusters are probably
      seeded onto the myocardium by vesicular transport from proepicardial villi, and
      our findings suggest that the resulting small, localised patches of epicardial
      cells might accelerate, supplement and tune the epicardial formation mediated by
      radial spreading of the epicardial sheet in the chick embryonic heart.

PMID- 11515596
TI  - Cytotoxicity of provisional crown and bridge restoration materials: an in vitro
      study.
AB  - There are numerous materials used to provide temporary coverage for teeth while
      permanent restorations are being fabricated. The biocompatibility of these
      materials is important for the protection of teeth and gingiva, but there is
      little information on this subject. This study aimed to examine possible time
      dependent toxic effects of provisional crown and bridge restoration materials,
      manipulated intraorally or extraorally, on epithelia cells. A total of 20 discs,
      4 sample discs from each product having dimensions of 4 mm diameter and 2 mm
      thickness, were prepared. After sterilization, toxicity of these discs was
      evaluated in the Madin Darby Bovine Kidney (MDBK) cell line. Morphological cell
      changes were observed microscopically at the 3rd, 6th, 12th, and 24th hours by
      the filter diffusion test method. After the 3rd hour, Artglass and Structur
      produced cytotoxic symptoms. Temdent had the least toxic effects at the end of
      the 12th hour. However, after the 24th hour, the toxic values were similar for
      all materials. The results of this study show that although the toxicity response
      of chemically and light curing materials had changed in different time periods,
      all of them had the same toxic effects at the end of the 24th hour.

PMID- 11515595
TI  - The value of routine antibiotic prophylaxis in mandibular third molar surgery:
      acute-phase protein levels as indicators of infection.
AB  - Postoperative infections in the oral region are usually caused by anaerobic
      bacteria. While some authors claim that routine antibiotic prophylaxis is
      necessary after third molar surgery, others do not recommend this practice. The
      major subject of controversy is what constitutes postoperative infection.
      Previous studies that have examined the benefit of routine antibiotic prophylaxis
      have used several clinical symptoms (pain, swelling, and trismus) as indicators
      of infection; however, these clinical symptoms may be vague and unreliable, and
      cannot be evaluated scientifically. As a result, their use has only sparked more
      debate in this area of research. The present study assessed the value of routine
      antibiotic prophylaxis in impacted mandibular third molar surgery using acute
      phase protein levels as potential indicators of early and late postoperative
      infection. Specifically, serum levels of C-reactive protein and alpha-1
      antitrypsin were measured preoperatively and postoperatively in patients who
      received either prophylactic antibiotics or placebos. The results revealed no
      statistically significant difference between treated and control patients in
      terms of incidence of postoperative infection.

PMID- 11515597
TI  - Monitoring of extracellular dopamine levels in the dorsal striatum and the
      nucleus accumbens with  5-minute on-line microdialysis in freely moving rats.
AB  - We report a reliable 5-min on-line monitoring of dopamine released from the
      dorsal striatum and the nucleus accumbens of rats using in vivo brain
      microdialysis. The detection limit for dopamine was approximately 20 fg in a 10
      microl injection sample using high-performance liquid chromatography with
      electrochemical detection set-up. Basal levels of dopamine in the dorsal striatum
      and the nucleus accumbens 4 h after probe insertion were 2.65 +/- 0.30 pg/5 min
      and 1.57 +/- 0.31 pg/5 min, respectively, whereas those of 20 h after probe
      insertion were lower: 0.97 +/- 0.21 pg/5 min and 0.51 +/- 0.09 pg/5 min,
      respectively. Infusion of the sodium channel blocker, tetrodotoxin (TTX; 2
      microM), essentially suppressed levels of dopamine in both brain areas. At 4 h
      after probe insertion, TTX perfused for 4 h via dialysis probe reduced levels of
      dopamine to 0.47 +/- 0.08 pg/5 min (80% reduction) in the dorsal striatum and to
      0.56 +/- 0.19 pg/5 min (65% reduction) in the nucleus accumbens. At 20 h after
      probe insertion, a similar TTX perfusion more rapidly reduced levels of dopamine
      to 0.05 +/- 0.01 pg/5 min (95% reduction) in the dorsal striatum and to 0.08 +/-
      0.01 pg/5 min (85 % reduction) in the nucleus accumbens. These results suggest
      that relatively fast changes in extracellular dopamine levels in these two brain
      areas can reliably be followed by this in vivo microdialysis technique.

PMID- 11515598
TI  - Adenomatoid hyperplasia of the palate mimicking clinically as a salivary gland
      tumor.
AB  - This report describes an illustrative case of adenomatoid hyperplasia (AH) of the
      minor salivary glands on the palate of a 31-year-old man. The clinical features
      of the present lesion corresponded with those of pleomorphic adenoma, but
      histologically large lobules of normal-appearing mucous acini were found. The
      cell proliferative activity demonstrated in histological sections, by an
      immunohistochemical staining of proliferating cell nuclear antigen and Ki-67,
      showed no statistically significant differences among AH and a matched control
      group of normal palatal salivary glands. This case suggests that AH apparently
      exhibits an idiopathic, focal hypertrophic lesion of intraoral mucous glands with
      limited growth potential.

PMID- 11515599
TI  - Neurosensory function and implant survival rate following implant placement with
      nerve transpositioning: a case study.
AB  - In patients with extensive bone resorption, implant placement posterior to the
      mental foramen is a problematic surgical procedure. This paper reports the
      results in 6 patients (aged 20-61) with edentulous areas in the posterior part of
      the mandible, in whom 26 Nobelpharma implants were placed, including 17 with
      transposition of the inferior alveolar nerve allowing the use of implant fixtures
      of at least 10 mm in length. Subsequent neurosensory function, based on British
      Medical Research Council definitions, and implant survival rate were examined. In
      all cases, postoperative numbness occurred in the lower lip and mental area.
      Three years after surgery, while one patient had completely recovered
      neurosensory function, five patients still experienced partial numbness, although
      this was not perceived as a problem by those patients. The implant survival rate
      was 100% approximately three years after surgery. The results suggest that a
      higher implant survival rate is likely when longer fixtures are used, but this is
      also more likely to lead to slight long-term neurosensory dysfunction.

PMID- 11515600
TI  - Concentration of 137Cs in dried Lentinula edodes (Shiitake) as an indicator of
      environmental contamination.
AB  - We analysed the concentration of radioactive cesium in dried Lentinula edodes
      (Shiitake) produced in Japan, and evaluated its use as an indicator of
      radioactive contamination. We collected Lentinula edodes (Shiitake) mushrooms
      grown on wood in 38 prefectures from north to south, and measured 137Cs, 134Cs
      and 40K concentrations with high purity Ge-detectors. The concentration ranges
      were as follows: 137Cs <0.003-61.1 Bq/kg, 40K 378.7-667.3 Bq/kg; 134Cs was
      undetectable. There was a positive correlation between 137Cs concentrations in
      Shiitake and those in rain and dry fallout (P < 0.05). They were also correlated
      inversely with atmospheric temperature (P < 0.01). The multiple correlation
      coefficient comparing 137Cs concentration with atmospheric temperatures, 40K
      concentrations and fallout levels was 0.56 which was statistically significant (P
      < 0.01). A variance analysis based on the 137Cs concentration classified by
      geographical area (Hokkaido-Tohoku, Kanto, Chubu, Kinki, Chugoku, Shikoku and
      Kyushu) showed that the variance between the groups was significantly greater
      than that within each group which, together with the above-mentioned information,
      suggests that the 137Cs levels are affected primarily by these environmental
      factors.

PMID- 11515601
TI  - A bibliographical survey of bruxism with special emphasis on non-traditional
      treatment modalities.
AB  - After proposing a common-sense definition of bruxism, this partial review
      distills its various symptoms and consequences from the literature. That
      literature suggests that the splint-the most popular treatment modality-falls
      short in some respects. The research literature is even less sanguine about the
      efficacy of such other traditional therapies as sound alarms and stress
      reduction. Given the limited success of traditional approaches, and given,
      moreover, the high incidence of bruxism and its harmful consequences, clinicians
      may occasionally be interested in experimenting with non-intrusive, safe, less
      widely known, treatment modalities. To meet this need, this review-unlike all
      other reviews of the subject-focuses on such comparatively unpopular or recent
      approaches.

PMID- 11515602
TI  - Histological and analytical studies of a tooth in a patient with cleidocranial
      dysostosis.
AB  - A histopathological and analytical study of a permanent tooth from a patient with
      cleidocranial dysostosis (CCD) was performed. The patient was a 47-year-old
      woman, who had 10 erupted permanent teeth and 2 partially erupted and 19
      completely impacted teeth, including supernumerary teeth. The erupted right upper
      premolar was extracted and observed using a light microscope and an electron
      probe X-ray microanalyzer (EPMA). Findings showed enamel hypoplasia,
      predominantly irregular globular dentin and Tomes' granular layer, and a complete
      lack of cellular cementum in the ground section. The incremental von Ebner and
      counter Owen lines were obscure. Comparative quantitative analysis using the EPMA
      showed that the quantities of calcium and phosphate were lower in the enamel and
      dentin than those of the control sample.

PMID- 11515603
TI  - Histopathological and immunohistological analyses in IgA deficient lymphoplasia
      (aly/aly) mouse.
AB  - The aly/aly mouse has a severe immunodeficiency, because it lacks peripheral
      lymph nodes as well as IgA and IgG immunoglobulin synthesis. In the present
      study, we performed histopathological and immunohistological examinations to
      clarify histological disorders of various immune organs in these mice. Carbon
      CH40 injections into the apex of the tongue confirmed the absence of
      submandibular lymph nodes in aly/aly mice. The thymus had a poorly constructed
      cortex and medulla, and the number of lymphoid follicles was clearly decreased in
      the spleen. No IgG- or IgA- producing cells were found in any immune organs,
      including the mucosal immune sites, though several IgM -producing cells were
      identified. Other characteristic findings included perivascular lymphocytes
      accumulation in the salivary glands, lungs, liver and pancreas, which caused
      tissues damage. These results demonstrated that the various lymphoid tissues
      disorders and organ-specific lymphocyte infiltration cause immuno-deficiency in
      the aly/aly mouse.

PMID- 11515605
TI  - Platelet storage lesion and apoptosis: are they related?
AB  - The relationship between the platelet storage lesion (PSL) and programmed cell
      death (apoptosis) is poorly understood. Nevertheless, there is some experimental
      evidence that platelets contain most of the components of the apoptosis machinery
      and both the apoptotic process and the PSL lead to platelet activation and
      microvesiculation with expression of phosphatidyl serine (PS) on the outer layer
      of cell membrane, a hallmark of all nucleated cells. The PS exposure is believed
      to contribute to the development of inflammatory or immunomodulation process, to
      the regulation of haemostatic balance and the ultimate clearance of dead or
      fragmented cells from the circulation. While there is no doubt that apoptosis, as
      a form of genetically encoded programmed cell death in nucleated cells, is
      triggered by several signalling stimuli at the nuclear level, there is some doubt
      as to whether platelets, as enucleated cells have retained the memory of the
      "parental" megakaryocytes for apoptosis or whether platelet mitochondrial DNA has
      a major role in both the apoptotic process and the PSL. The storage lesion occurs
      during processing and storage subsequent to mechanical trauma, hypoxic conditions
      or exposure to cold. In this brief report some observational evidence is provided
      in support of the notion that the PSL and apoptosis may be related to each other,
      despite the fact that, in contrast to the 'parental' megakarocyte, the platelets
      appear to survive upon stimulation with a high concentration of protein kinase
      inhibitors such as staurosporine (STS), in the presence of cycloheximide (CHX)
      which inhibit protein synthesis. This is a model which is often used to regulate
      the level of survival signals. The possible relevance of platelet
      microvesiculation to transfusion practice is briefly discussed.

PMID- 11515604
TI  - Ankylosis of the temporomandibular joint caused by rheumatoid arthritis: a
      pathological study and review.
AB  - Rheumatoid arthritis (RA) of the temporomandibular joint (TMJ) in a 59-year-old
      Japanese woman is reported, including details of clinical, histopathological and
      radiological findings. The patient had been diagnosed as having RA of the right
      knee joint 41 years previously, and suffered from arthralgia of the right TMJ.
      Radiological examination showed a radiopaque lesion of the mandibular head and
      mandibular fossa in the right TMJ and ankylosis of the right TMJ was diagnosed on
      the basis of the clinical and radiological findings. Condylectomy was performed.
      Pathological examination of material from the joint region revealed a marked
      increase of collagen fibers associated with slight capillary dilatation and
      hemorrhage. The final diagnosis was ankylosis of the right TMJ due to RA. The
      literature on TMJ ankylosis secondary to RA is reviewed and discussed.

PMID- 11515606
TI  - Recent developments in hemoglobin-based oxygen carriers--an update on clinical
      trials.
AB  - Considerable progress has been made in the development of the hemoglobin based
      oxygen carriers (HBOCs), with a number of products in the final stages of
      clinical development prior to licensing application. This follows many years of
      concentrated study. Although there are limitations to the clinical use of the
      currently studied HBOCs, there are a number of advantages that suggest that these
      products will have an important role in future clinical practice. It is
      anticipated that these products will be commercially available within two years.

PMID- 11515607
TI  - The effect of G-CSF on lymphocyte subsets and CD34+ cells in allogeneic stem cell
      transplantation.
AB  - The effect of granulocyte colony-stimulating factor (G-CSF) on peripheral blood
      lymphocytes (PBL) and CD34+ cell frequency in the apheresis product has been
      determined in 25 healthy stem cell donors. Peripheral blood mononuclear cells
      (PBMNC) were collected after five days of G-CSF 10 microg/kg/day s.c., which was
      well tolerated. The median number of leukocytes increased eight-fold over that of
      pretreatment levels. Collection of PBMNC lasted a median of two (range, 1-3)
      days. The mean mononuclear cell (MNC) count and total lymphocyte percentage were
      6.69 x 10(8)/kg and 59.08%, respectively, and the frequency of CD34+ cell
      expression was 2.1% in the apheresis product. The frequency of CD3+, CD4+, CD25+,
      NK and CD122+ cell expressions in mobilized PBMNC and PBL showed no significant
      difference. However, the frequency of CD8+, CD8+28+, CD3+DR+, CD19+, CD20+ and
      CD22+ B cells expression in the apheresis product increased significantly
      compared to steady-state PBL. In contrast, the frequency of the CD11 a+ and
      CD8+38+ cell expressions in the apheresis product was decreased compared to the
      steady-state PBL. The mean yield of CD34+ and CD3+ cells were 13.6 x 10(6) and
      2.69 x 10(8)/kg of recipient body weight (RBW), respectively. Following allograft
      all patients engrafted with >0.5 x 10(9)/l neutrophil and < or = 20 x 10(9)/l
      platelets on a median of day 13 and 12, respectively. Nine patients had grade II
      IV acute GVHD and chronic GVHD occurred in eight patients. Four patients died due
      to transplant-related complications. There was one late engraftment failure which
      occurred on the fifth month. Thirteen patients are still alive. In conclusion,
      these results indicate that administration of G-CSF at 10 microg/kg/day in normal
      donors alters the lymphocyte subsets and there are significant differences in the
      lymphocyte contents of the recipients before apheresis and in apheresis product.

PMID- 11515608
TI  - Seroprevalence of hepatitis C virus (HCV) infection among blood donors: a
      hospital-based study.
AB  - Insofar as chronic hepatitis C virus (HCV) infection in many individuals is
      asymptomatic, and as the prevalence of antibodies to hepatitis C virus (anti-HCV)
      among blood donors in Lebanon is scarce, this study addressed the prevalence of
      anti-HCV in 5,115 blood donors. Data obtained were compared to other world
      regions. Of the blood donors screened, 57 were initially tested positive or
      doubtful for anti-HCV Ab. Subsequent testing by two-third generation enzyme
      immunoassays confirmed that, of the 57 initially tested positive/doubtful, only
      18 were positive for anti-HCV giving a prevalence rate of 0.4%. While there was
      no difference in HCV prevalence with respect to age or gender, a higher rate was
      seen in non-Lebanese compared to Lebanese subjects (3.4% vs 0.3%, P < 0.001).
      These results demonstrate a low prevalence of HCV infection among Lebanese blood
      donors, which was comparable to those established for western countries.

PMID- 11515609
TI  - Current precision of immunological extracorporeal plasma treatment.

PMID- 11515610
TI  - Apheresis registry in Sweden: scope, techniques and indications for treatment. A
      report from the Swedish apheresis study group.
AB  - Registries of therapeutic apheresis can be used to evaluate changes in
      technology, clinical indications and applications over the years. This study
      reports data collected prospectively and voluntarily in Sweden during 1993-1999.
      A total number of 40 apheresis units have been performing therapeutic apheresis
      procedures: 16 blood centers, 20 dialysis units, two intensive care units, one
      hematology ward and one hemotherapy unit. The registry includes a median of 92%)
      of the centers for therapeutic apheresis in Sweden during the years and in 1999
      there were 31 active units in 26 hospitals. The total numbers of procedures per
      year have remained fairly stable corresponding to a median of 46 treatments/
      100,000 inhabitants, and in 1999 4084 procedures were performed. The number of
      plasma exchanges has decreased, but LDL-apheresis and immunoadsorption procedures
      have increased over the years. 70% of the patients have been referred for 12
      indications. A significant decline was found for patients with SLE and Guillain
      Barres syndrome. The use of extracorporeal photo-chemotherapy has increased over
      the years, and 3 indications include >75$ of the patients. There has been an
      adaptation to the experience learned by different studies. The number of
      collections of hematopoietic progenitor cells is about 9/100,000 inhabitants, and
      in 1999 821 collections were performed. The use of allogeneic donors is
      increasing. The extent of therapeutic apheresis in Sweden was compared to other
      countries on the basis of published data. In Sweden, the extent of therapy is two
      to three-fold to that for Canada and France.

PMID- 11515611
TI  - The current state of extracorporeal haemorheotherapy: from haemodilution via
      cascadefiltration to rheohaemapheresis.
AB  - Rheological therapy aims at an improvement of organ perfusion however, it has to
      be stressed that the tonus of the blood vessels also plays an important role for
      both the blood distribution and the rheology in the micro- and the
      macrocirculation. Conventional rheotherapy consists of attempts to influence
      nutrition and life style, to apply drugs such as purin derivatives,
      vasodilatating or defibrinising substances and hypervolaemic (using infusion
      therapy), hypovolaemic, e.g., blood letting, erythrocytapheresis and--the most
      widely distributed- -isovolaemic haemodilution. With the introduction of
      centrifugal devices, and approximately 10 years later with the introduction of
      hollow fibre and flat sheet membrane techniques, a considerable increase of
      therapeutical efficacy was achieved. These technologies were successfully applied
      for the treatment of cellular and plasmatic hyperviscosity syndromes. The
      treatment of less severe diseases of the micro- and macrocirculation, vessel
      stenosis, vessel wall sclerosis, malformation of the blood vessel architecture,
      pathological clinical-chemical blood parameters and maldistribution have hardly
      been taken into consideration. Our group at Koln investigated different plasma
      differential separation techniques and demonstrated, that adsorption as well as
      filtration could be applied. These different techniques being 6-10 times more
      effective as conventional haemodilution techniques have in common high molecular
      weight proteins determining the viscosity of plasma and thus whole blood
      viscosity is removed, however differences among the different elimination
      techniques do exist. The rheological and clinical importance of such differences
      has to be determined. Applying filtration techniques for both primary and
      secondary separations, the concept of Rheohaemapheresis was developed. A
      corresponding quality program was also introduced into our clinical routine.
      Rheohaemapheresis is supported from the currently introduced concept of the
      synergetic consideration of the microcirculation. Age related macular
      degeneration, so far without generally accepted therapy, is a most advanced
      indication based on several pilot studies and a prospective, randomised
      controlled trial. Other diseases of the microcirculation have also successfully
      been treated.

PMID- 11515612
TI  - Evaluation of dosed red blood cell units collected with Gambro BCT--TRIMA.
AB  - The increasing need of collecting high quality blood components and of improving
      the overall productivity of a blood centre requires the utilisation of a new
      innovative process that combines high speed collection with an automated process
      and blood component tailoring to fit individual patient requirements. We
      collected dosed Red Blood Cell (dRBC) units on 64 donors, eligible as regular
      donors on the Gambro BCT TRIMA using the dRBC collection protocol. The collection
      target was set to 180 ml packed Red Blood Cells (pRBCs) in 225 ml total
      collection volume (n = 7), or 300 ml pRBCs in 375 ml total collection volume (n =
      33) or 360 ml in 450 ml (n = 24), depending on donor's hematological profile and
      blood volemia. Saline was infused as the replacement fluid at a 120%)
      collection:infusion ratio. Donor per cent hematocrit was (mean +/- S.D.) 43.7 +/-
      4.0% and TBV = 4.99 +/- 0.69 1. The procedures yielded 100 +/- 6% of predicted
      yield, with a hematocrit of 78.2 +/- 6.6% in 29 +/- 3 min. Hb content was 99.9 +/
      21.8 in all procedures, or 61.5-94.4-118.6 g in the three groups, respectively.
      After the addition of the SAG-M storage solution, the hematocrit was 56.3 +/-
      6.2%. No adverse reactions have been reported by the donors and all pPRBC units
      were transfused to patients without any transfusion reaction being reported by
      clinicians. The dRBC protocol is well tolerated by donors without any side
      effects, other than normal effects of regular blood donation. Higher pRBC
      productivity can be reached with a safe and automated process in conjunction with
      a high and consistent product quality easily matching the donor collection
      criteria and pRBC unit standards. Tailoring of pRBC units can result in an
      improved patient transfusion support.

PMID- 11515613
TI  - Double plateletpheresis (DPA) and tailored RBC collection with the Excel-Pro:
      preliminary results.
AB  - The Dideco Excel-Pro is frequently used for double plateletpheresis (DPA) when
      the platelet precount exceeds 280 x 10(3)/l. Platelets are collected as "dry
      platelets" and the resuspension solution is added when the procedure is over.
      Even when DPA is carried out the product volume prior to resuspension may be as
      low as 60 ml. As a result, a third product may be collected along with platelets.
      Our priority is to collect RBCs and, depending on the donor's BW, tailored RBC
      collections are carried out. This means that from 400 to 480 ml of PRBC (70% hct)
      are collected from donors whose BW exceeds 75 kg. The results of the last 27
      DPA/tailored PRBC collections are: Donors gender and BW (kg), 19M/8F: 88.4 +/-
      7.3 Hemoglobin (g/dl): 15.4 +/- 1.3 Platelet precount (x 10(3)/microl): 308 +/-
      45 Volume of blood processed (1): 5.5 Procedure time (min): 81 +/- 3 Platelet
      yield (x 10(11)): 6.8 +/- 0.6 Avg Hemoglobin content of PBRC (g): 102.6 +/- 12.3
      WBC contamination of the platelets: 6.8 +/ -10(5).

PMID- 11515614
TI  - Red cell apheresis in autologous preoperative blood donation.
AB  - Preoperative autologous blood donation (PAD) is a commonly used technique for
      elective surgical procedures with a predictable blood loss. The conventional
      method is to collect one unit whole blood weekly several times within the shelf
      life of red cell concentrates. Erythrapheresis with the Haemonetics cell
      separator MCS-3p or plus makes it possible to collect two units of red cells in
      one single session and with this option the time interval and operation can be
      prolonged to three weeks to improve erythropoiesis. 295 patients, who were
      scheduled for hip replacement or knee endoprothesis were evaluated
      retrospectively calculating the net profit of red cells after donating two units
      of red cells by erythrapheresis. The median net profit of red cells was 140 ml
      red cells but with a wide range. The patients who profit most of PAD were those
      with a predonation hct below 42% who had net profits up to 300 ml red cells due
      to an increased erythropoiesis, which compensate for the withdrawal of the red
      cells. Thus erythrapheresis with the Haemonetics MCS-3p or Haemonetics MCS plus
      is recommended for patients with a predonation hct lower than 42% and who can be
      scheduled for PAD at least 3 weeks before operation when two units of red cells
      are the target for PAD.

PMID- 11515615
TI  - Large volume leukapheresis with AMICUS cell separator in peripheral blood stem
      cell autologous transplant.

PMID- 11515616
TI  - A prospective randomised concurrent comparison of the COBE Spectra Version 4.7,
      COBE Spectra Version 6 (auto PBSC) and Haemonetics MCS+ cell separators for
      leucapheresis in patients with haematological and non-haematological
      malignancies.
AB  - A prospective study of the CD34+ cell collection efficiency of three cell
      separators was undertaken comparing the mononuclear cell, CD34+ cell and CFU-GM
      yield. Twenty patients were entered in the study, all had received mobilising
      chemotherapy and daily G-CSF (5 microg/kg subcutaneously). The first
      leucapheresis was performed when the peripheral blood absolute CD34+ cell count
      was > or = 20 cells/microl. All patients underwent two leucaphereses on
      consecutive days. The patients were randomised to undergo either the first or
      second leucapheresis using the COBE Spectra Version 4.7 and then randomised to
      either the COBE Spectra Version 6 or Haemonetics MCS+ for the other
      leucapheresis. The target durations of the procedure on the COBE Spectra Version
      4.7 and Version 6 were 180 min or two total blood volumes (TBV), and for the
      Haemonetics MCS+ was 20 cycles with four recirculations. All machines were
      operated on the 1997 software supplied by the respective manufacturers. The time
      taken for the procedure was significantly longer with both the Haemonetics MCS+
      and the COBE Spectra Version 6 than the COBE Spectra Version 4.7. Both COBE
      Spectra versions processed significantly larger volumes of blood than the
      Haemonetics MCS+. The absolute yield of mononuclear cells, CFU-GM and CD34+ cells
      were all significantly lower with the Haemonetics MCS+ compared with both COBE
      Spectra Versions, as were the yields per unit volume of blood processed. There
      was no significant difference in the reduction in the platelet count following
      leucapheresis with any of the machines.

PMID- 11515617
TI  - The molecular epidemiology and clinical significance of TT virus (TTV) infection
      in healthy blood donors from southern Taiwan.
AB  - To evaluate the molecular epidemiology and clinical significance of th

PMID- 11515618
TI  - Cellular contamination of plasma collected with various apheresis systems.
AB  - Efforts to improve the purity of blood products have mainly focused on reducing
      white blood cell (WBC) levels in cellular blood products. Relatively little
      attention has been given to the cellular purity of plasma. We evaluated plasma
      units collected on six apheresis systems: Dideco Excel, Haemonetics-MCS+,
      Fresenius-AS-Tech 204, Baxter-Amicus, Gambro BCT COBE Spectra and Gambro BCT
      Trima. Collected plasma volumes averaged 300-350 ml for the various systems.
      Plasma samples were analyzed for platelet (PLT) content (Technicon H3, Bayer) and
      residual WBC (Imagn 2000). Results are given below. Platelet levels were
      consistently low for MCS+, COBE Spectra and Trima (all <50 x 10(3) microl(-1)),
      and were highest with AS204. Residual WBC levels were relatively low in all
      systems except MCS+. Extremely low levels were observed in Trima plasma. All of
      the Trima and Spectra units contained <1 x 10(6) WBC per product. With Excel, AS
      Tech 204 and Amicus, 1 to 2 units were found to have >1 x 10(6) WBC, while almost
      all units from MCS+ exceeded this limit. Different levels of plasma purity were
      obtained with different apheresis systems. The Gambro BCT COBE Spectra and Trima
      systems were found to achieve consistently low levels of both platelets and WBC.

PMID- 11515619
TI  - The outcome in myasthenia gravis patients--an eight-year follow-up after
      finishing immunoabsorption therapy.
AB  - Eight years ago four patients suffering from myasthenia gravis (MG) type C and E
      according to Compston with failed drug therapy were treated three times (one
      patient 11 times) by protein A immunoabsorption (Immunosorba, Excorim, Fresenius
      Hemocare GmbH, StWendel, Germany). No further immunoabsorption treatments have
      been carried out. In addition, three patients were given a thymectomy. The
      present status of the patients was checked six and eight years thereafter. We
      could see a beneficial effect in all MG patients. The patients are fit for work;
      all have an improved Besinger index. The patients were used as their own
      controls. A higher anti-AChR-ab level six years after protein A immunoabsorption
      than at the beginning was seen in all patients combined with a less serious MG.
      In addition, their immunomodulation could be induced as seen in lymphocyte and
      inflammatory protein changes during the first 36 days after beginning
      immunoabsorption treatment. A larger population has to be investigated to verify
      these results.

PMID- 11515620
TI  - Apoptotic UV-irradiated lymphocytes undergo protease mediated shedding of L
      selectin in vitro.
AB  - Adhesion between circulating lymphocytes and endothelial cells of the vessel wall
      depends on the expression of selectins and is the first step of tissue invasion
      which characterises inflammation. UV-B is well known to induce apoptosis in
      lymphocytes. We show that induction of apoptosis by any procedure leads to a
      metalloprotease mediated shedding of L-selectin from the surface of T
      lymphocytes. Together with the previously published immunosuppressive action of
      apoptotic cells, this may contribute to the clinical effect of UV-B application,
      especially in photopheresis.

PMID- 11515621
TI  - Supra-oesophageal complications of reflux disease.

PMID- 11515622
TI  - Prolonging proton pump inhibitor-based anti-Helicobacter pylori treatment from
      one to two weeks in duodenal ulcer: is it worthwhile?
AB  - AIMS: To compare the efficacy of one-week versus two-week treatment with
      lansoprazole, amoxycillin and clarithromycin in inducing healing of Helicobacter
      pylori-positive duodenal ulcers as well as to investigate the role of several
      factors, determinant in the ulcer healing process. PATIENTS AND METHODS: Seventy
      one active duodenal ulcer patients were randomised to receive one- or two-week
      treatment with lansoprazole (30 mg bid), clarithromycin (500 mg bid) and
      amoxycillin (1 g bid), not followed by any additional acid suppressive therapy.
      Ulcer healing and Helicobacter pylori infection were assessed by endoscopy and
      urea breath test 4 weeks after the end of treatment. Before entering the trial
      and four weeks after the end of treatment, dyspeptic symptoms were recorded and
      scored by a validated questionnaire. The potential effects of a number of
      clinical variables on the ulcer healing process were evaluated by means of
      univariate and multivariate analyses. RESULTS: Duodenal ulcer was healed in 80.5%
      patients treated for one week and in 91.4% patients treated for 2 weeks according
      to intention-to-treat analysis (p=NS). Ulcer healing was more frequent in the
      Helicobacter pylori cured patients compared to those with persisting infection
      (90.9% vs 68.5%; p=0.04). Multivariate analysis did not reveal any significant
      predictor of duodenal ulcer healing. CONCLUSIONS: Two-week treatment with
      lansoprazole, amoxycillin and clarithromycin, without continuation of
      antisecretive therapy, is better, although the difference is not statistically
      significant, than one-week treatment in healing Helicobacter pylori-positive
      duodenal ulcer disease. The eradication of Helicobacter pylori is the most
      important factor related to ulcer healing.

PMID- 11515623
TI  - Could the duration of anti-Helicobacter pylori treatment be shorter?

PMID- 11515624
TI  - Discrepancy between Helicobacter pylori stool antigen assay and urea breath test
      in the detection of Helicobacter pylori infection.
AB  - BACKGROUND: The reference diagnostic methods available for detection of
      Helicobacter pylori infection are either invasive (histology) or expensive and
      highly sophisticated (Urea Breath Test). A new enzyme immunoassay, which can be
      easily performed in any laboratory, has been developed to detect Helicobacter
      pylori in stool specimens (HpSA-Meridian Diagnostics, Cincinnati, USA). Aim of
      the study was to compare HpSA to Urea Breath Test. PATIENTS AND METHODS: A total
      of 125 patients (52 never treated for Helicobacter pylori infection and 73 after
      Helicobacter pylori eradication therapy) referring to our Department, underwent
      both tests within two weeks. RESULTS: Contrasting results between the two tests
      were found in 30% of cases: in 19% of the untreated patients and in 37% of the
      treated patients (p<0.001). The main discrepancy consisted in positive HpSA
      associated with negative Urea Breath Test. Mean HpSA value in such conditions was
      0.273 optical density, while in patients with both positive tests, it was 1.192
      optical density. In untreated, but not in treated patients, raising the HpSA cut
      off value significantly decreased the percentage of conflicting results.
      CONCLUSIONS: Some disagreement was detected between HpSA and Urea Breath Test
      results, especially in treated patients. Possible explanations for our findings
      are a low HpSA cut off value together with the identification of Helicobacter
      pylori coccoid forms by the immunoassay but not by the urease based Urea Breath
      Test. The higher percentage of discrepancy detected in treated patients might
      support this hypothesis.

PMID- 11515625
TI  - Is the stool test out of breath?

PMID- 11515626
TI  - Bacterial supplementation in the irritable bowel syndrome. A randomised double
      blind placebo-controlled crossover study.
AB  - BACKGROUND: Symptoms of at least a subgroup of patients with irritable bowel
      syndrome may be associated with an alteration in gut flora. Studies on bacterial
      based therapy have yielded mixed results. AIMS: To determine if oral
      administration of the probiotic Lactobacillus casei strain GG under randomized
      placebo controlled conditions improves symptoms in irritable bowel syndrome
      patients with bloating related symptoms. PATIENTS: A total of 25 patients with
      clinically confirmed irritable bowel syndrome (Rome criteria) were enrolled in
      the study. METHODS: This was a randomised double-blind placebo-controlled
      crossover trial. Lactobacillus GG was administered as enterocoated tablets
      constituting a daily dosage of 10(10) colony forming units. Symptoms were
      assessed by daily symptom diaries and periodic questionnaires. RESULTS: Twenty
      four patients were randomised; 19 (80%) female, mean age 40 years (range 24-60),
      mean duration of symptoms 4.9 years (range 0.5-18). Nineteen (80%) patients
      completed the study. No significant differences were found between Lactobacillus
      casei strain GG and placebo mean symptom scores for pain, urgency or bloating. A
      trend was noted, however, for a reduction in the number of unformed bowel motions
      on Lactobacillus casei strain GG treatment for patients with diarrhoea.
      CONCLUSIONS: Lactobacillus casei strain GG alone did not significantly improve
      symptoms in this irritable bowel syndrome subgroup. A "diarrhoea predominant"
      subgroup may warrant further investigation.

PMID- 11515627
TI  - Probiotics: could they turn out to be ineffective in irritable bowel syndrome?

PMID- 11515628
TI  - Troxipide, a novel antiulcer compound, has inhibitory effects on human neutrophil
      migration and activation induced by various stimulants.
AB  - BACKGROUND: Neutrophils are considered to be involved in the pathogenesis of
      Helicobacter pylori-associated gastroduodenal diseases on account of their potent
      biological functions as effector cells. Troxipide, a new antiulcer compound used
      for patients with gastric ulcer or gastritis, has been shown to inhibit migration
      and activation of guinea pig neutrophils, but little is known about the
      pharmacological effects on human neutrophils. AIMS: To study the effects of
      troxipide on chemotactic migration and superoxide generation by human
      neutrophils. METHODS: The chemotactic response of neutrophils was determined in a
      multi-well chamber with a polycarbonate filter and the generation of O2- by
      neutrophils was measured using a chemiluminescence method. Concentrations of
      troxipide in gastric mucosa were measured by high-performance liquid
      chromatography. RESULTS: Incubation of neutrophils with 10(-6) to 10(4) M
      troxipide caused inhibition of recombinant interleukin-8-induced migration. These
      concentrations of troxipide also inhibited superoxide generation by neutrophils
      stimulated by formyl-methionyl-leucyl-phenylalanine or platelet activating
      factor. These phenomena were not simply due to the direct cytotoxic effects since
      the above concentrations of troxipide did not induce neutrophil apoptosis. The
      concentrations of troxipide detected in the gastric mucosa after oral
      administration were in the range able to inhibit chemotactic migration and
      superoxide generation by neutrophils in vitro. CONCLUSION: These results suggest
      that troxipide may exert its therapeutic effect in patients with gastric ulcer or
      gastritis by inhibiting inflammatory responses and mucosal injury mediated by
      neutrophils in gastric mucosa.

PMID- 11515629
TI  - Staging and survival of colorectal cancer: are we making progress? The 14-year
      experience of a Specialized cancer Registry.
AB  - BACKGROUND AND AIMS: It is still unclear whether recent advancements in
      colorectal cancer research have led to an improvement in management and prognosis
      of the disease. Through the data of a specialized colorectal cancer Registry we
      aimed at analysing pathological staging and 5-year survival of all patients with
      malignancies of large bowel diagnosed between 1984 and 1997. Main objective was
      to ascertain whether or not we are making progress in the control of this common
      neoplasm. PATIENTS AND METHODS: During the 14-year period 1984-97, a total of
      2,240 colorectal cancer patients were registered, for a crude incidence rate of
      64.5 and 55.2/100,000/year in males and females, respectively Tumours were staged
      with "Tumour, Node, Metastasis" system, corresponding to Dukes' classification,
      into four main groups. Survival was assessed with Life Table analysis, and
      statistical significance--between various subgroups--evaluated with Log-Rank
      Test. RESULTS: Crude incidence rates of colorectal neoplasms showed minor
      fluctuations during initial period of registration, increasing sharply after 1990
      mainly due to localized (stage I and II) lesions and, to a lesser degree, to
      stage III tumours. Number of advanced (stage IV and unstaged) malignancies
      remained virtually stable. When results were expressed as percent of total cases,
      the fraction of localized lesions increased from 39% in the biennium 1984-5 to
      51.6% in 1986-97, and the proportion of advanced tumours fell from 39% to 21.6%
      (p for trend <0.001). As expected, 5-year survival was significantly (p<0.002)
      more favourable for individuals diagnosed in 1990-91 than for patients registered
      in 1984-89. CONCLUSIONS: In Northern Italy, incidence rates of colorectal
      carcinoma are rising. This trend is associated with a sharp increase of newly
      detected localized lesions and with a significant improvement of overall 5-year
      survival. The result may be attributed to several concomitant factors, such as:
      A] wider use of colonoscopy, B) increased education of patients, C) more
      attention given to symptoms.

PMID- 11515630
TI  - Competition in liver transport between chenodeoxycholic acid and ursodeoxycholic
      acid as a mechanism for ursodeoxycholic acid and its amidates' protection of
      liver damage induced by chenodeoxycholic acid.
AB  - BACKGROUND: Ursodeoxycholic acid has been widely used as a therapeutic agent in
      cholesterol gallstones and liver disease patients, but its mechanism of action is
      still under investigation. AIMS: The protective effect of ursodeoxycholic acid,
      both free, taurine and glycine conjugated, against hepatotoxic bile acids such as
      chenodeoxycholic acid and its taurine amidate was studied in bile fistula rats
      and compared with the cholic and taurocholic acid effect. METHODS:
      Tauroursodeoxycholic acid, glycine ursodeoxycholic acid, ursodeoxycholic acid,
      taurocholic acid and cholic acid were infused iv over 1 hour (8 micromol/min/kg)
      together with an equimolar dose of either taurochenodeoxycholic acid or
      chenodeoxycholc acid. Bile flow, total and individual bile acid and biliary
      lactate dehydrogenase and alkaline phosphatase enzymes were measured. RESULTS:
      Taurochenodeoxycholic acid and chenodeoxycholc acid caused cholestasis and liver
      damage associated with a decreased bile flow, total and individual bile acids
      secretion accompanied by a biliary leakage of lactate dehydrogenase and alkaline
      phosphatase enzymes. Tauroursodeoxycholic acid, glycine ursodeoxycholic acid,
      ursodeoxycholic acid and taurocholic acid, on the contrary, were choleretic,
      inducing an opposite effect on biliary parameters. Simultaneous infusion of
      taurochenodeoxycholic acid and the protective bile acid resulted in a functional
      and morphological improvement of the above parameters in the following order:
      glycine ursodeoxycholic acid > tauroursodeoxycholic acid > ursodeoxycholic acid
      followed by taurocholic acid; cholic acid was ineffective. CONCLUSIONS: The
      results show the protective effect of glycine ursodeoxycholic acid,
      ursodeoxycholic acid and tauroursodeoxycholic acid. This may be due to a
      facilitated transport of the toxic bile acid into bile; conjugation with taurine
      is less effective than glycine. Finally, the better protective effect of
      ursodeoxycholic acid and its amidates with respect to cholic acid and its taurine
      conjugated form seems to be related to their different lipophilicity and micellar
      forming capacity.

PMID- 11515631
TI  - High serum levels of secretory immunoglobullin A in chronic pancreatitis.
AB  - BACKGROUND AND AIM: Elevated levels of secretory immunoglobulin A have been
      reported in patients with cholestatic hepatitis. Secretory immunoglobulin A is
      present in the biliary and pancreatic tract. Chronic pancreatitis is a disease
      characterized by dilatation of Wirsung's duct. The aim of the study was to
      evaluate secretory immunoglobulin A levels in patients suffering from chronic
      pancreatitis. PATIENTS AND METHODS: The study population consisted of 66
      consecutive chronic pancreatitis patients (55 male, 11 female; mean age 49.6+/-10
      years), 26 patients suffering from acute recurrent pancreatitis (9 males, 17
      females; mean age 39.6+/-10.6 years) and 90 healthy controls, pair-matched for
      sex and age with the chronic pancreatitis patients. Secretory immunoglobulin A
      was determined by enzyme-linked immunosorbent assay, as were serum alanine
      transaminase and GGT. RESULTS: Secretory immunoglobulin A levels were
      significantly higher in chronic pancreatitis patients (35+/-23.7 mg/l) than in
      those acute recurrent pancreatitis group (16.1+/- 7.9) and in healthy controls
      (11.8+/-4.9 mg/l) (p<0.0001). Secretory immunoglobulin A was significantly higher
      in chronic pancreatitis patients with steatorrhoea, diabetes and calcifications
      and in those undergoing pancreatic surgery. Of 61 chronic pancreatitis patients,
      14 (23%) had pathological GGT. When only chronic pancreatitis patients with
      normal GGT levels were analysed, the differences in secretory immunoglobulin A
      levels between groups of patients and between chronic pancreatitis subgroups
      remained statistically significant. CONCLUSIONS: This study demonstrates that
      secretory immunoglobulin A is elevated in chronic pancreatitis. Its value in the
      staging of patients needs to be further evaluated.

PMID- 11515632
TI  - Flumazenil in the treatment of acute hepatic encephalopathy in cirrhotic
      patients: a double blind randomized placebo controlled study.
AB  - AIMS: The aim of this study was to evaluate the effects of flumazenil on hepatic
      encephalopathy in patients with liver cirrhosis. PATIENTS AND METHODS: . In the
      double blind randomized, placebo controlled study, 54 patients with hepatic
      encephalopathy grade III-IV were randomly assigned to receive either flumazenil 2
      mg iv (group A) or placebo (group B); conventional treatment with branched-chain
      amino acid, saline, glucose, and lactulose was administered in both groups. A 24
      hour observation period was established. Clinical improvement was defined as a 3
      point decrease in the Glasgow coma score at any time within 24 hours. RESULTS:
      Clinical improvement was obtained in 22/28 patients in group A and in 14/26 in
      group B (p<0.05); improvement was observed within the first six hours in 21/22
      patients in group A and only in 3/14 in group B. Mortality rate was not different
      between group A and B; however, all 6 non-responders in group A and only 5 out of
      12 in group B died within 24 hours. Among patients with post-bleeding
      encephalopathy, 11 out of 17 in group A and only 2 out of 14 in group B improved
      (p<0.001). CONCLUSIONS: Flumazenil may exert a beneficial effect in a subset of
      patients with acute hepatic encephalopathy; encephalopathy associated with
      bleeding is more likely to respond to flumazenil; responders to the treatment
      usually improve within the first 6 hours while lack of response usually
      represents a bad prognostic sign.

PMID- 11515633
TI  - Endoscopic therapy of adenomas of the papilla of Vater. A retrospective analysis
      with long-term follow-up.
AB  - AIMS: To compare the efficacy and the complication rate between endoscopic snare
      resection of adenomas of Vater's papilla and endoscopic palliation. METHODS: In a
      retrospective, non randomized manner, we compared long-term results of our
      endoscopic strategies in 36 patients with histologically confirmed adenoma of
      Vater's papilla submitted either to local endoscopic snare resection (n=18) or to
      simple endoscopic palliation (n= 18), respectively. RESULTS: Between 1985 and
      1998 results were reviewed. Median age was 76.5 (range 42-89) years in the
      palliation, and 64.0 (23-89) years in the endoscopic snare resection group.
      Median duration of follow-up was 33 (6-135) and 75.0 (27-123) months,
      respectively. The incidence of adenocarcinoma of Vater's papilla was 1 per 52.8
      patient-years after endoscopic snare resection and 1 per 15.5 patient-years in
      the group treated with endoscopic palliation. Compared to the results of
      endoscopic palliation (prosthesis, sphincterotomy), we found a significant
      reduction of carcinoma-related death (p=0.0045, McNemar) and adenoma carcinoma
      sequence (p=0.007, McNemar) after snare resection. CONCLUSIONS: This
      retrospective study suggests that complete endoscopic snare resection of adenomas
      of Vater's papilla will lead to a lower rate of adenoma-carcinoma sequence, to a
      lower carcinoma-related death rate and probably improves patient survival. These
      results should be proven prospectively.

PMID- 11515634
TI  - Surgical treatment of hepatocellular carcinoma in cirrhosis.
AB  - Hepatocellular carcinoma is one of the most frequent forms of cancer worldwide
      and its diagnosis and treatment have changed substantially during the last few
      years. Recent advances in ultrasonography, spiral computed tomography scan and
      nuclear magnetic resonance have further simplified the diagnostic approach to
      hepatocellular carcinoma. Ultrasonography is the reference examination, giving a
      wide variety of information on tumour size, location, relationship with portal
      and hepatic veins and splanchnic haemodynamics. Surgical resection and liver
      transplantation can both be defined as curative treatment while other techniques
      such as percutaneous ethanol injection and chemoembolization must be considered
      as palliative. Therapeutic strategies for hepatocellular carcinoma are based upon
      data concerning the characteristics of the tumour the functional status of non
      tumoural liver parenchyma and patients' general conditions. Surgery of
      hepatocellular carcinoma in cirrhotic liver is mainly restricted by lack of
      functional hepatic reserve and by the limited capacity of hepatic regeneration.
      The best surgical results are obtained in early tumoural stages which generally
      need limited resection. Nevertheless, major liver resections have a specific role
      in selected cases. Recurrence rate after surgical resection is high and is
      related to a large number of factors. For this reason, liver transplantation,
      removing at the same time, the tumour and the underlying disease, is considered,
      theoretically, the best treatment for hepatocellular carcinoma, but its role is
      still debated and limited by difficult organ sharing. Integration of present
      therapeutic schemes are under evaluation with promising preliminary results.

PMID- 11515635
TI  - Ambulatory oesophageal pH-metry. Position paper of the Working Team on
      Oesophageal pH-metry by the GISMAD (Gruppo Italiano di Studio sulla Motilita
      dell'Apparato Digerente).
AB  - In the last three decades, oesophageal pH monitoring has progressed from a
      physiological research tool to a routine outpatient clinical investigation in
      patients with suspected gastro-oesophageal reflux disease, one of the most common
      gastrointestinal disorders. Technological progress has considerably simplified
      both the procedure and the interpretation of data obtained, and there is
      currently reasonable consensus as to the parameters that best discriminate
      between physiological and pathological reflux. There remains a need for
      internationally agreed definitions and standards with regard to indexes to
      quantitate the extent and the significance of the relationship between occurrence
      of symptoms and reflux episodes during the examination. It is felt that national
      or local normal values are to be used to circumvent different eating habits and
      other socio-cultural differences which may influence gastro-oesophageal reflux.
      The reproducibility of the test appears, at present, to be at least good enough
      to allow classification of the patient as a pathological or physiological
      refluxer, albeit wide day-to-day variations seem to exist as far as concerns the
      extent of gastro-oesophageal reflux. Clinical applications of the technique have
      increased with better knowledge of the protean clinical manifestations of gastro
      oesophageal reflux disease, and include the evaluation of "typical" gastro
      oesophageal reflux disease patients with negative endoscopy or refractory
      oesophagitis, the "atypical" manifestations of gastro-oesophageal reflux disease
      and the pre- and post-operative evaluation of patients undergoing antireflux
      surgery.

PMID- 11515636
TI  - Dietary habits and dental health over the first 18 months of life.
AB  - OBJECTIVES: The main objective of this study was to describe the dental health of
      infants and toddlers with special reference to their dietary habits and oral
      hygiene behaviour over the first 18 months of life. METHODS: The longitudinal
      dietary data were obtained at 6, 12 and 18 months of age by using a 3-day weighed
      diet diary. Dental examinations were carried out at 12, and again at 18 months of
      age. The information on demographic factors and oral hygiene behaviours over the
      first 18 months of life was gathered by using a structured questionnaire at 12
      and 18 months. RESULTS: 163 children were studied. Visible dental plaque was
      present in 18% and 25% of children at 12 and 18 months of age, respectively. No
      child had dental caries at either 12 or 18 months of age. There was a
      statistically significant correlation between visible plaque measured as plaque
      index at 12 months and the mean daily eating/drinking episodes at 6 months
      (r=0.25, P=0.001) and 12 months (r=0.15, P=0.05). The correlations between plaque
      index at 18 months and the mean eating/drinking episodes at both 12 months
      (r=0.2, P=0.04) and 18 months (r=0.2, P=0.02) were low but statistically
      significant. Nevertheless, there was no significant correlation between
      accumulation of plaque at either 12 or 18 months and the mean daily frequency
      consumption of food and drink containing non-milk extrinsic sugars (NMES) at any
      age. Children who brushed their teeth themselves were more likely to have visible
      plaque compared with children whose teeth were cleaned by their parents. The
      partial correlation showed that positive relation between mean daily
      eating/drinking episodes and plaque was not influenced by tooth brushing.

PMID- 11515637
TI  - Salt fluoridation and dental caries in Jamaica.
AB  - PURPOSE: In 1987, Jamaica initiated a comprehensive island-wide salt fluoridation
      program. A survey was conducted in 1995 to monitor the impact of salt
      fluoridation among children in Jamaica. METHODS: Dental examinations of 1,120
      children aged 6-8, 12, and 15 years were conducted according to World Health
      Organization criteria to assess dental caries, fluorosis, the presence of and
      need for dental sealants, and Community Periodontal Treatment Needs (CPI).
      RESULTS: Age specific DMFT means observed in 1995 were 0.2 at age 7, 0.4 at age
      8, 1.1 at age 12 and 3.0 at age 15. The mean DMFT scores in children 6, 12 and 15
      years of age were dramatically lower than the corresponding scores of 1.7, 6.7
      and 9.6 obtained at the baseline examination in 1984 for children of the same age
      groups, respectively (baseline data for 7- and 8-year-olds were not collected).
      The mean percentage of sound permanent teeth for all age groups was 90% in 1995.
      The percentage of children caries-free at baseline was 27.6% for 6 years, 2.8%
      for 12 years and 0.3% for 15 years of age. In 1995, the percentage of caries-free
      children (permanent teeth) was 61%. In 1984, 23 children were scored as having
      very mild or mild fluorosis. In 1995, five children were scored in the same
      categories of fluorosis, using Dean's criteria; thus, fluorosis remained at
      negligible levels in 1995. CONCLUSIONS: The oral health survey conducted in
      Jamaica in 1995 indicated a significant decline in dental caries compared with
      findings in 1984. The major change in Jamaica during the interval was the
      introduction of salt fluoridation in 1987. Dental fluorosis was low in the 1995
      survey.

PMID- 11515638
TI  - Effectiveness of an oral health education programme in primary schools in
      Zimbabwe after 3.5 years.
AB  - Many medical and dental professionals in African nations believe that school
      teachers, through attendance of a short workshop, can be trained to provide oral
      health education. This increases the number of professionals available and is
      regarded as an important way forward in improving oral health. OBJECTIVES: The
      current study assesses the effectiveness of an oral health education programme
      administered by schoolteachers in a district in Zimbabwe over a period of 3.5
      years. METHODS: The experimental group consisted of schools that had sent
      representatives to a regional workshop on oral health held in 1992. The control
      group was selected at random from schools not having attended the workshop. A
      total number of 439 boys and 526 girls were examined in 1992. Follow-up
      evaluations were carried out in 1993, 1994 and 1996. The dependent variables were
      plaque accumulation and caries increment in grade 2 and grade 4 children of
      experimental and control schools. RESULTS: ANOVA test with year of evaluation
      (1992-94), experiment/control school, age and gender as independent variables
      showed no statistically significant difference in mean plaque scores in
      longitudinally examined original grade 2 (P>0.20) and grade 4 children (P=0.06)
      from experimental and control schools. The mean caries increment score in the
      experimental and control schools was 0.04 and 0.19, respectively. ANOVA test with
      fluoride levels and gender as independent variables on caries increment in
      experimental and control schools did not show a statistically significant
      difference (P=0.06). CONCLUSION: The one-time training of teachers in aspects of
      oral health was ineffective in lowering plaque levels over a period of 3.5 years.
      Considering the low caries increment observed over the study period, the effect
      of the oral health programme on caries levels in the study group was
      inconclusive.

PMID- 11515639
TI  - Recurrent oral ulcerations associated with recurrent herpes labialis--two
      distinct entities?
AB  - We investigated the prevalence of recurrent aphthous ulcerations (RAU) and
      recurrent herpes labialis (RHL) in a young adult population. The study group
      consisted of 20,689 soldiers (aged 18-21 years, mean 19.8 +/- 1 years). There
      were 14,991 men and 5,698 women. Every patient was asked to complete a self
      report health questionnaire which requested information about the occurrence of
      either RAU or RHL. Data were analyzed using the chi-square test, and the odds
      ratio was also determined. The prevalence of RAU and RHL was 6.2% and 5.4%,
      respectively. The prevalence among women was significantly higher (P<0.001), than
      among men for both RAU (7.1% and 5.8%, respectively) and RHL (6.8% and 4.9%,
      respectively). Among women, the chance of having RAU for those who were RHL
      positive was 6.88 greater than for those RHL negative. Among men, the chance of
      having RAU for those who were RHL positive was 12.37 greater than for those RHL
      negative. In women, the chance of having RHL for those who were RAU positive was
      6.88 greater than for those who were RAU negative. In men, the chance of having
      RHL for those who were RAU positive was 12.37 greater than for those who were RAU
      negative. It is concluded that a similar underlying pathological process or
      unknown cofactor may be involved in both RAU and RHL.

PMID- 11515640
TI  - Dental erosion in children and adolescents--a cross-sectional and longitudinal
      investigation using study models.
AB  - OBJECTIVE: To investigate the prevalence and incidence of dental erosion in
      children and adolescents. METHODS: Lesions were registered for all tooth surfaces
      of primary and permanent teeth using pre-orthodontic study models. A total of
      1,000 individuals (mean age 11.4+/-3.3 years) were included; 265 of them were
      followed over a 5-year period using their final orthodontic casts. RESULTS: In
      the primary teeth, 26.4% of the individuals had no erosive lesions, 70.6% had at
      least one tooth with grade 1 erosion and 26.4% had grade 2 erosion. Grade 1
      erosion was found in 44% of the occlusal surfaces of molars (36% of the incisal
      surfaces of the canines) and grade 2 erosion in 11% (9%). Lesions affecting oral
      or vestibular surfaces were negligible. In the permanent teeth, 11.6% of
      individuals had at least one tooth with grade 1 erosion but only 0.2% had at
      least one tooth with grade 2 erosion. The most affected teeth were the mandibular
      first molars (7% with grade 1 lesions). Lesions affecting oral or vestibular
      surfaces were negligible. Mandibular first molars were identified as possible
      marker teeth for the onset of erosive lesions. Within the last two decades, the
      percentage of subjects with at least one tooth with a grade 1 or 2 erosive lesion
      significantly increased for primary and with grade 1 for permanent teeth (P< or
      =0.001). The longitudinal observation revealed that subjects with erosive lesions
      in their primary dentition had a significantly increased risk for erosion in
      their permanent teeth (P< or =0.001). CONCLUSION: In Germany, dental erosion
      seems to be a significant, but not a serious, problem for dental health in
      adolescents.

PMID- 11515641
TI  - Oral melanin pigmentation related to smoking in a Turkish population.
AB  - OBJECTIVE: Besides genetic factors, tobacco smoking has been found to be the
      major cause of oral melanin pigmentation. The purpose of the present study was to
      evaluate the frequency of oral melanin pigmentation in a Turkish population and
      to present its correlation with clinical parameters relevant to periodontal
      status in current smokers, non-smokers, former smokers. METHOD: A sample of 496
      patients was randomly selected. The subjects were interviewed regarding their
      smoking habits. They were clinically examined by a single examiner for the
      presence of oral melanin pigmentation in different oral mucosal regions. The same
      examiner recorded the clinical parameters including GI (gingival index), PI
      (plaque index), BOP (bleeding on probing), PD (probing depth) and GR (gingival
      recession). Examiner 2 completed a questionnaire concerning skin color and
      smoking habits. RESULTS: In the study group, 41% were current smokers, 46%
      nonsmokers and 13% former smokers. The frequencies of pigmented areas were
      significantly higher in current smokers than in those without any smoking habits.
      The clinical parameters revealed similar findings for all groups. Low GI and BOP
      values were observed for current smokers when compared with non-smokers and
      former smokers, respectively. GI values were significantly associated with the
      pigmentations in gingiva. CONCLUSIONS: The results of our study show that smokers
      in a Turkish population had significantly more pigmented oral surfaces than
      nonsmokers.

PMID- 11515642
TI  - Caries preventive effect of sugar-substituted chewing gum.
AB  - OBJECTIVES: The aim of this 3-year community intervention trial was to determine
      the caries preventive effect of sugar-substituted chewing gum among Lithuanian
      school children, and to assess compliance with the instructions for gum use.
      METHODS: A total of 602 children, aged 9-14 years, from 28 school classes in five
      secondary schools in Kaunas, Lithuania, were given a baseline clinical and
      radiographic caries examination. The schools were randomly allocated to receive
      one of the following interventions: sorbitol/carbamide gum; sorbitol gum; xylitol
      gum; control gum; and no gum. Children in the four active intervention groups
      were asked to chew at least five pieces of gum per day, preferably after meals.
      The children were reexamined clinically after 1, 2 and 3 years, and
      radiographically after 3 years. Self-reported compliance was monitored
      anonymously four times during the study. RESULTS: A total of 432 children were
      available at the 3-year clinical follow-up examination. The crude mean 3-year
      caries increments (DMFS--all stages of lesion formation) were 11.8 for the
      sorbitol/carbamide gum group; 9.0 for the sorbitol gum group; 8.1 for the xylitol
      gum group; 8.3 for the control gum group; and 12.4 for the no gum group. The
      adjusted 3-year caries increments were statistically significantly lower in the
      sorbitol gum group, the xylitol gum group and the control gum group than in the
      no gum group, whereas no statistically significant difference was seen between
      the no gum group and the sorbitol/carbamide gum group. Adjusted 3-year caries
      increments in the xylitol gum group and the sorbitol gum group did not differ
      statistically significantly from the caries increments in the control gum group.
      Compliance with the study protocol was better in School C (xylitol gum) than in
      the other schools. In all schools, compliance decreased over time. CONCLUSION:
      The results indicate that the caries preventive effect of chewing sugar-free gum
      is related to the chewing process itself rather than being an effect of gum
      sweeteners or additives, such as polyols and carbamide.

PMID- 11515643
TI  - Improving oral health in institutionalised elderly people by educating
      caregivers: a randomised controlled trial.
AB  - OBJECTIVES: This cluster-randomised controlled trial assessed whether oral health
      care education (OHCE) for nursing home caregivers would achieve improvements in
      clients' oral health. METHODS: Twenty-two nursing homes were randomly allocated
      to intervention or control group. Clients were examined at baseline and at follow
      up visits 1- and 6-months after caregivers received OHCE. Main outcome measures
      were denture plaque, denture-induced stomatitis, dental plaque and gingivitis.
      Differences in group means/medians were compared with adjustment for cluster
      randomisation. RESULTS: Clients' baseline oral health was poor. After OHCE, the
      intervention group's oral health scores improved significantly. Reductions in
      denture plaque scores (0-4 scale) exceeded those of the control group by 1.15
      (95%CI=0.83, 1.47) at 1 month and by 1.47 (95%CI=1.13, 1.80) at 6 months. Denture
      induced stomatitis prevalence reduced significantly over 6 months compared to the
      control group (P<0.0001). Group differences in favour of the intervention group
      were 0.41 (95%CI=0.18, 0.65) at 1 month and 0.34 (95%CI=0.14, 0.53) at 6 months
      for dental plaque (0-3 scale), and 0.17 (95%CI= -0.01, 0.35) at 1 month and 0.28
      (95%CI 0.15, 0.42) at 6 months for gingivitis (0-2 scale). Key differences
      remained significant after adjustment for clustering effects. The provider's
      costs would currently be approximately pounds 6700 per year to deliver the
      intervention to a Health Authority with 100 homes. CONCLUSIONS: Although final
      levels of residents' oral health were still short of ideal, this study clearly
      shows that, for a modest cost, OHCE can improve caregivers' knowledge, attitudes
      and oral health care performance for elderly, functionally dependent clients.

PMID- 11515644
TI  - A comparison of retention and the effect on caries of fissure sealing with a
      glass-ionomer and a resin-based sealant.
AB  - OBJECTIVE: To compare the retention and the caries preventive effect of a glass
      ionomer developed for fissure sealing (Fuji III) and a chemically polymerized
      resin-based fissure sealant (Delton). DESIGN: A split mouth randomized design
      using contralateral teeth. SETTING: WHO Regional Demonstration, Training and
      Research Center for Oral Health, Damascus, Syrian Arab Republic. SAMPLE AND
      METHODS: 179 children, 7 years old at the start of the study, were recruited from
      schools close to the Center. Only children with at least one pair of permanent
      first molars that were caries free or only had incipient lesions were included in
      the study. Follow-up examinations for sealant retention were done after 6 months,
      1 year, 2 years and 3 years. The number of children available for reexamination
      was 129 (after 6 months); 121 (after 1 year); 115 (after 2 years) and 116 (after
      3 years). Four dental hygienists were trained in the sealant procedures and did
      approximately one fourth of the sealants each. RESULTS: After 3 years the glass
      ionomer sealant was completely lost in almost 90% of the teeth compared to less
      than 10% of the resin sealed teeth. After 3 years the relative risk of a tooth
      sealed with glass-ionomer over that of a tooth sealed with resin was 3.38 (95%
      CL: 1.98; 5.79). This finding was consistent over type of tooth. CONCLUSIONS: The
      glass-ionomer sealant tested in the present study had poorer retention and less
      caries protective effect than the resin-based sealant used.

PMID- 11515645
TI  - On the retention and effectiveness of fissure sealant in permanent molars after
      15-20 years: a cohort study.
AB  - The aim of the present study was to clinically evaluate fissure sealants on the
      occlusal fissures and buccal pits of permanent first and second molars after 20
      and 15 years, respectively. The population consisted of 72 children, each of whom
      had had their four first molars sealed between 1977 and 1980. At the annual
      examinations, all caries-free, newly erupted second molars were sealed. When
      sealant was applied to the second molars, the first molars were checked and
      sealant was reapplied to those that had deficient sealants. At the follow-up,
      when the subjects were 26-27 years of age, 27 in the original group had moved
      from the community. Thus, the present result is based on 45 subjects. One hundred
      and fifty-three sealed first molars and 161 sealed second molars were available
      for inspection. At the follow-up examination of the first molars 20 years after
      sealant had been applied, 65% showed complete retention, 22% partial retention
      without caries, and 13% caries or restoration in the occlusal fissures or buccal
      pits. At the 15-year follow-up of the second molars, the corresponding figures
      were 65%, 30%, and 5%, respectively. Of the restored or carious molars,
      significantly more were found in the mandible than in the maxilla (P<0.001). This
      longitudinal study showed that pit and fissure sealants--applied during childhood
      -have a longlasting, caries-preventive effect.

PMID- 11515646
TI  - Dentists' decisions on prophylactic removal of mandibular third molars: a 10-year
      follow-up study.
AB  - OBJECTIVES: In recent years, several critical outcome studies concerning the
      prophylactic removal of mandibular third molars have been published. These would
      appear to motivate a more restrictive approach today as compared with 10 years
      ago. The aim of the present study was to examine dentists' decisions on the
      prophylactic removal of impacted mandibular third molars over a 10-year period.
      METHODS: Thirty-six cases were selected so as to represent an equal distribution
      of males and females, ages, angular position and degree of impaction of the
      molar. Twenty-six general dental practitioners (GDPs) and 10 oral surgeons judged
      the same cases on two occasions 10 years apart. RESULTS: Calculated for each
      category of dentists, there was no significant difference in the mean number of
      molars designated for removal between the two occasions. Two GDPs and three oral
      surgeons presented a higher removal rate, whereas five GDPs presented a lower
      removal rate on the second occasion as compared to the first one. The dentists
      presented a considerable interindividual variation in removal rate, between 0 and
      22 molars on the first occasion and between 0 and 25 molars on the second
      occasion. CONCLUSION: In the decisions on prophylactic removal of mandibular
      third molars, there has been no change over the last 10 years towards a more
      noninterventionist attitude. Thus, the dentists seem not to have been influenced
      by the evidence that this intervention is not cost-effective.

PMID- 11515647
TI  - Re: Tickle M, Kay EJ, Bearn D. Socio-economic status and orthodontic treatment
      need. Community Dent Oral Epidemiol 1999; 27:413-8.

PMID- 11515648
TI  - Electrolyte diffusion of cesium bromide in water at 25 degrees C.
AB  - Electrolyte diffusion coefficients of CsBr in water have been measured using
      137Cs isotope with an open ended capillary technique without stirring. The
      measurements were done at 25 degrees C over the concentration range of 10(-6) 
      0.25 M and the measured values are compared with the theoretical values of
      diffusion coefficients estimated on the basis of Onsager-Fuoss theory. At low
      concentrations, there is a good agreement between the experimental and
      theoretical values of diffusion coefficients. The deviations at higher
      concentrations are explained on the basis of the occurrence of ion-ion
      interactions.

PMID- 11515649
TI  - Production, concentration and deep purification of 111In radiochemicals.
AB  - A new method of 111In separation from a silver target irradiated with 30 MeV
      alpha-particles is described. The 111In isolation from Ag and Cd is based on its
      co-precipitation with La(OH)3. The 111In separation from La(III) has been
      performed by the method of ion-exchange chromatography. A multi-stage
      purification technique was developed that allows the production of 111In
      radiochemicals in which the part of impurities of di-, tri-valent metal atoms is
      negligible.

PMID- 11515650
TI  - A study of Rhizophora spp wood phantom for dosimetric purposes using high-energy
      photon and electron beams.
AB  - Previous scattering and depth-dose investigations involving use of the Malaysian
      hardwood Rhizophora spp have shown this medium to produce good agreement with
      measurements made in water. Present study extends the comparison, now including
      measurements of percentage depth-dose made for photons at 6MV and 5 and 12MeV
      electron beams. For the 6 MV photon and 5 MeV electron beams, discrepancies
      between percentage depth-dose for Rhizophora spp and water, at all depths, are
      found to be within 2.6 and 2.4% respectively. At 12 MeV electron energies,
      measured percentage depth-doses in Rhizophora spp beyond 3.5cm depth are found to
      be in significant discord with those for water. The absorbed dose in water
      measured in Rhizophora spp at d(max) for all three beams produces discrepancies
      of no more than 1.1% when compared with measurements made in water.

PMID- 11515651
TI  - Excitation functions of 124Te(d,xn)124,125I reactions from threshold up to 14
      MeV: comparative evaluation of nuclear routes for the production of 124I.
AB  - Excitation functions of the nuclear reactions 124Te(d,xn)124-125I were measured
      from their respective thresholds up to 14.0 MeV via the stacked-foil technique.
      Thin samples were prepared by electrolytic deposition of 99.8% enriched 124Te on
      Ti-backing. The excitation function of the 124Te(d,n)125I reaction was measured
      for the first time. The present data for the 124Te(d,2n)124I reaction are by an
      order of magnitude higher than the literature experimental data but are in good
      agreement with the results of a hybrid model calculation. From the measured cross
      sections, integral yields of 124,125I were calculated. The energy range Ed = 14 -
      > 10 MeV appears to be the best compromise between 124I-yield and 1251-impurity.
      The calculated 124I-yield amounts to 17.5 MBq/microA h and the 125I-impurity to
      1.7%. A critical evaluation of the three nuclear routes for the production of
      124I, viz. 124Te(d,2n)-, 124Te(p,n)- and 125Te(p,2n)-processes, is given. The
      reaction studied in this work proved to be least suitable. The 124Te(p,n)
      reaction gives 124I of the highest radionuclidic purity, and a small-sized
      cyclotron is adequate for production purposes. The 125Te(p,2n)-reaction is more
      suitable at a medium-sized cyclotron: the yield of 124I is four times higher than
      in the other two reactions but the level of 0.9% 125I-impurity is relatively
      high.

PMID- 11515652
TI  - Labelling of the solvent DMSO as side reaction of methylations with n.c.a.
      [11C]CH3I.
AB  - Competing labelling of solvent dimethyl sulfoxide (DMSO) can occur during the 11C
      methylation of amine precursors. A kinetic analysis of the methylation reaction
      of DMSO with n.c.a. [11C]CH3I was performed at 120 degrees C resulting in rate
      constants. The rate constant for the formation of the intermediate, methylated
      DMSO ([11C]DMSO-M), is compared to the reaction of [11C]CH3I with two tertiary
      amines, namely Dexetimide and Desmethyloxotremorine-M. The specific activity of
      the labelled product is reduced due to partial 12C-methylation of the precursor
      amines by [11C]DMSO-M in cases of significant DMSO labelling as side reaction.

PMID- 11515653
TI  - The measurement of photoneutrons in the vicinity of a Siemens Primus linear
      accelerator.
AB  - This study involves the measurement of photoneutron contamination emitted from a
      Siemens Primus medical linear accelerator by using BD-PND bubble detectors.
      Various bubble detectors were arranged around the linac head with the interval of
      I m and at the same height as the isocenter to measure the dose equivalent
      distribution in the treatment room. The measurements were performed for 15 MV X
      rays with 40 x 40cm2 and 0 x 0cm2 fields and for 15,18, and 21 MeV electrons with
      25 x 25 cm2 electron cone. Neutron dose equivalent rate at the points of
      measurement in the treatment room decreased with increasing distance to the
      isocenter. The maximum neutron dose equivalents were at the isocenter, and the
      values for 15MV 40 x 40 and 0 x 0 cm2 were 1843+/-90 and 169.9+/-59.9 microSv per
      Gy X-ray, respectively. The values for 15, 18 and 21 MeV electrons with 25 x 25
      cm2 cones were 100.0+/-20.4, 262.7+/-61.2 and 349.0+/-29.6 microSv per Gy
      electron, respectively. The neutron contamination of electrons less than 12 MeV
      was below the detection limit.

PMID- 11515654
TI  - Photon radiation dose enhancement at material interfaces.
AB  - Experimental radiation dose-effect studies at a material's interface require high
      resolution dose measurements resulting from the exposure of mounted samples on a
      supporting substrate. Reflections of photons and electrons from the substrate
      increase the effective dose to the sample relative to dose from the direct beam
      incident on the unbacked sample. This difficult-to-measure enhancement of
      effective dose can be calculated easily with Monte Carlo transport codes. We have
      used the Monte Carlo code, CYLTRAN, to carry out radiation transport and dose
      calculations in very thin water layers backed by different substrate materials.
      We present cases with an incident photon beam (15-100 keV) on a water medium with
      five different substrates--mylar, aluminum, copper, silver, and gold.

PMID- 11515655
TI  - 137Cs contained in books printed during the 1960s in Japan.
AB  - Radioactivity values of 137Cs in printed pages and covers of hardbound books
      issued during the 1960s in Japan were measured by gamma-ray spectrometry. The
      result showed that the main source of 137Cs present in the books was rice straw
      used to make the backing board of covers. The 1965 peak of 137Cs content of the
      book was explained by the variation of 137Cs content of rice straw with the
      harvest year and a change of the kind of board.

PMID- 11515656
TI  - The response of high-purity germanium detectors to X-rays with energy in the
      region of the Ge K-absorption edge.
AB  - The response of a high-purity germanium detector to X-rays in the 8-15-keV energy
      region has been investigated. The w-value and energy resolution dependencies on
      the X-ray energy have been studied. No abrupt variation of w is observed at the
      germanium K absorption-edge (11.104-keV). The detector energy resolution follows
      a characteristic linear dependence on Ex(-1/2) over the whole energy range. Both
      features are consistent with the absence of intrinsic nonlinearity effects in
      germanium at the K-edge.

PMID- 11515657
TI  - Persistence of dicentrics in Chernobyl clean-up workers who suffered from low
      doses of radiation.
AB  - Blood samples from 243 clean-up workers who undertook duties at Chernobyl in 1986
      were examined in order to study temporal changes of chromosomal aberrations over
      long periods (6-12 yr) following irradiation. From an analysis of the elapsed
      time between irradiation and cytogenetic examination, it was found that the
      frequency of dicentrics and rings did not decrease during the 6 yr period of
      observation.

PMID- 11515658
TI  - Dosimetry with radiochromic films: a document scanner technique, neutron
      response, applications.
AB  - The possibility of reading radiochromic films by the employment of a document
      scanner and associated software was explored. Dosimetric characteristics, such as
      the sensitivity of the technique, reproducibility in dose assessment, minimum
      detectable dose, film uniformity, OD variation with time, variation of OD due to
      multiple scans, polarity of the analyzing light, fast neutron response and
      thermal neutron yield were investigated. The technique was used to measure dose
      distributions in stereotactic radiotherapy, orthovoltage treatment and neutron
      capture therapy.

PMID- 11515659
TI  - Installation and calibration of Kayzero-assisted NAA in three Central European
      countries via a Copernicus project.
AB  - An account is given of the installation and calibration of k0-based NAA--assisted
      by the DSM Kayzero/Solcoi software package--at the KFKI-AEKI, Budapest, the NPI,
      Rez and the IJS, Ljubljana. Not only the calibration of the Ge-detectors and the
      irradiation facilities are discussed, but also other important topics such as
      gamma-spectrometric hard- and software, QC/QA of the IRMM-530 Al-Au flux monitor
      and the upgrade of the Kayzero/Solcoi code. The work was performed in the
      framework of a European Copernicus JRP, coordinated by the Laboratory of
      Analytical Chemistry, Gent, with DSM Research, Geleen, as the industrial partner.

PMID- 11515660
TI  - Radon activity concentrations and effective doses in ancient Egyptian tombs of
      the Valley of the Kings.
AB  - Radon concentrations and equilibrium factors were measured in three pharaonic
      tombs during the year 1998. The tombs, which are open to the public are located
      in a limestone wadi on the West Bank of the River Nile at Luxor, 650 km south of
      Cairo. The radon activity concentration and equilibrium factor were measured
      monthly by two-integral nuclear track detectors (bare and diffusion detectors).
      Seasonal variation of radon concentrations, with summer maximum and winter
      minimum were observed in all tombs investigated. The yearly mean radon activity
      concentrations insidc the tombs ranged from 540 to 3115 Bq m(-3). The mean
      equilibrium factor over a year was found to be 0.25 and 0.32 inside and at the
      entrance, respectively. Estimated annual effective doses to tour guides ranged
      from 0.33 to 1.90 mSv, visitors receive doses from 0.65 to 3.80 microSv per
      visit. The effective dose to tomb workers did not exceed the 20 mSv yr(-1) limit.

PMID- 11515661
TI  - A mathematical model for calculation of 90Sr absorbed dose in dental tissues:
      elaboration and comparison to EPR measurements.
AB  - A mathematical model for calculation of the 90Sr absorbed doses in dental tissues
      is presented. The results of the Monte-Carlo calculations are compared to the
      data obtained by EPR measurements of dental tissues. Radiometric measurements of
      the 90Sr concentrations. TLD and EPR dosimetry investigations were performed in
      animal (dog) study. The importance of the irregular 90Sr distribution in the
      dentine for absorbed dose formation has been shown. The dominant dose formation
      factors (main source-tissues) were identified for the crown dentine and enamel.
      The model has shown agreement with experimental data which allows to determine
      further directions of the human tooth model development.

PMID- 11515662
TI  - Mechanically induced EPR signals in tooth enamel.
AB  - Sample preparation of tooth enamel for electron paramagnetic resonance (EPR)
      dosimetry usually involves mechanical operations. The present study shows that
      mechanical operations performed without water cooling generate a paramagnetic
      center inducing a stable isotropic EPR signal with g-value of 2.00320 and
      linewidth of about 0.1 mT. Using EPR spectrum simulation, the similarity between
      the mechanically induced signal and the signal generated when the enamel is
      heated in air at a temperature above 600 degrees C was investigated. Results
      indicate that the mechanically induced signal is related to sample temperature
      increase during mechanical friction.

PMID- 11515664
TI  - Vertical distributions of uranium, thorium and potassium and of volumetric heat
      production rates in the sediments of the Sao Francisco Basin, Central Brazil.
AB  - Uranium, thorium and potassium measurements and volumetric heat production rate
      calculations were made in Bambui Group Neoproterozoic sedimentary rocks from the
      Sao Francisco Basin, central Brazil. The measurements were made from drilling
      cuttings from two deep wells drilled near the cities of Alvorada do Norte,
      northeast Goias State, and Montalvania, north of Minas Gerais State. The obtained
      results allowed the construction of the vertical profiles depicting the
      abundances of heat generating elements, of the heat production rate and of U/Th,
      U/K and Th/K ratios in these sediments. These profiles, which reflect both the
      lithology and the sediment history. are used to interpret some aspects of the
      Bambui Group sedimentation sequence.

PMID- 11515663
TI  - Skin dose measurement by using ultra-thin TLDs.
AB  - The treatment schedule for radiation therapy is often interrupted because of
      complicated skin reactions. Quantitative information relating beam parameters and
      skin reactions will be helpful. Measurements were performed for 6-15 MV photons
      and 6-21 MeV electrons with ultra thin TLD films (GR-200F, surface area 0.5 x
      0.5cm2, nominal thickness 5 mg cm(-2)). The skin doses for various field sizes,
      ranging from 10 x 10 to 40 x 40 cm2, and various incident angles of beam from 0
      degrees to 80 degrees were measured. The ratios of skin dose to maximum dose in
      phantom for 10 x 10 cm2 are 16.10+/-0.68%, 14.03+/-1.04% and 10.59+/-0.64% for 6,
      10 and 15 MV, respectively. Such ratios increase with a larger field size. For
      electrons the ratios are 72.59+/-1.72%, 78.52+/-2.99%, 78.89+/-2.86%, 86.08+/
      2.62%. 87.75+/-1.94% and 86.33+/-3.09% for 6, 9, 12, 15, 18 and 21 MeV,
      respectively. They also increase with a larger size. The oblique factors also
      increase with larger incident angle.

PMID- 11515665
TI  - Coal face and stockpile ash analyser for the coal mining industry.
AB  - A portable nucleonic instrument was developed for the determination of coal ash
      on the coal face or the surface of coal stockpiles. The instrument employs the
      backscattered gamma-gamma technique. There are two gamma-ray sources used in this
      instrument: a 1.1 MBq 133Ba source as the primary source of radiation and a 37
      kBq 137Cs for gain stabilization. The instrument is commercially available.

PMID- 11515666
TI  - Variations in 7Be concentrations in the atmosphere of Kuwait during the period
      1994 to 1998.
AB  - The Beryllium-7 (7Be) concentrations in the atmosphere of Kuwait, as found by
      gamma-ray measurements for 243 air filters collected over a five-year period,
      produced variable values ranging from 0.2 to 14.9 mBq/m3 with a behavior pattern
      which has oscillatory characteristics, with increased activities occurring in the
      summer months of each year. The annual levels of occurrence of 7Be were found to
      be correlate with the cyclic pattern resulting from the eleven-year temporal
      variations associated with the solar activity.

PMID- 11515667
TI  - Natural radioactivity in groundwaters around a fertilizer factory complex in
      South of Spain.
AB  - A study of the concentration of the U isotopes, 226Ra and 230Th in a groundwater
      system has been carried out. This aquifer, located in the provinces of Sevilla
      and Huelva, is the most important in the south of Spain having a surface area of
      2500 km2. The proximity of a fertilizer factory complex to this aquifer system is
      of particular concern given that it releases a significant part of its waste
      directly into the estuary of the Odiel and Tinto rivers, also storing a further
      part on the right bank of the Tinto river. Investigation has been made of the
      environmental impact of the fertilizer factory, either as a result of leaching of
      radionuclides from the phosphogypsum piles or otherwise as a result of intrusion
      of the Odiel and Tinto waters, both of which are in close contact with the
      aquifer. Results show U concentration in waters of this system around the
      phosphogypsum piles to be significantly higher than those in other areas of the
      same aquifer. The low 226Ra concentrations found in the same locations add
      support to the origin of part of the U in these samples.

PMID- 11515668
TI  - Characterization of a maternal-fetal HIV transmission model using pregnant
      macaques infected with HIV-2(287).
AB  - To study mechanisms involved in mother-to-fetus transmission of human
      immunodeficiency virus (HIV) in utero, we have developed a chronically
      catheterized pregnant macaque model that permits simultaneous and sequential
      determination of virus in maternal and fetal blood and amniotic fluid during
      pregnancy. In this report, we have characterized this model using three groups of
      pregnant macaques designed to sample: (1) maternal blood, fetal blood, and
      amniotic fluid (n = 6); (2) maternal blood and amniotic fluid (n = 6); or (3)
      maternal blood only (n = 2). After inoculation with the highly pathogenic HIV
      2(287), all pregnant macaques developed brief but intense viremias followed by
      precipitous CD4+ T-cell declines within 2-3 weeks. While all the infants born to
      dams of the three groups were HIV positive, the degree of infection and outcome
      of HIV infection varied. All infants were shown to be HIV-RNA-positive by reverse
      transcriptase-polymerase chain reaction (RT-PCR). However, HIV-infected cells
      were detected only in the blood of those born to dams enrolled in groups 1 and 2:
      most of these infants progressed to CD4+ T-cell depletion. The infants in group 3
      exhibited HIV-RNA in plasma, although neither HIV-infected cells nor CD4+ T-cell
      depletion was detectable. However, all infants developed HIV-2-specific antibody
      at various levels by 2 months of age. Together, the data suggest that, while the
      degree of instrumentation may modulate intensity of virus transmission to fetus,
      the highly pathogenic HIV-2(287) exhibited a high frequency of virus transmission
      from the mother to fetus.

PMID- 11515669
TI  - CD3 polymorphism in cynomolgus monkeys (Macaca fascicularis).
AB  - Cynomolgus monkeys were divided into two groups in terms of the reactivity of
      their lymphocytes with the FN18 monoclonal antibody, which is directed to the CD3
      of rhesus monkeys. It was shown that 24 (12.2%) out of 196 monkeys did not have
      lymphocytes that reacted with the FN18, although T cells from those animals
      responded well to mitogenic stimulation. We have determined the nucleotide
      sequences of the CD3delta, CD3gamma, and CD3epsilon chains and found that two
      amino acids of the CD3epsilon chain of the FN18 non-reactive monkeys were
      different when compared with the FN18 reactive monkeys. Our results indicated
      that the CD3epsilon molecule of cynomolgus monkeys is polymorphic at the epitope
      level, which is recognized by the FN18 monoclonal antibody.

PMID- 11515670
TI  - Pregnancy and live birth from nonsurgical transfer of in vivo- and in vitro
      produced blastocysts in the rhesus monkey.
AB  - Embryo transfer in the rhesus monkey has been historically limited to transfer of
      cleavage stage embryos. In order to allow genetic manipulation of rhesus embryos
      in vitro, without using invasive surgical techniques, it is important to explore
      the transfer of morula and blastocyst stage embryos. Embryos were produced by in
      vitro fertilization from gonadotropin-stimulated monkeys, or were obtained by
      nonsurgical uterine flushing of naturally mated or artificially inseminated
      females. Nonsurgical transfer was accomplished by inserting a metal guide through
      the cervix into the uterus, after which a hollow cell sampler was inserted over
      the guide. The guide was removed and a catheter was inserted containing one to
      five embryos. Several pregnancies resulted from in vitro- and in vivo-derived
      blastocysts, and two pregnancies were carried to term resulting in one live
      birth. Blood samples were collected regularly to monitor plasma levels of
      chorionic gonadotropin, luteinizing hormone, and progesterone. The recipients
      received progesterone as a subcutaneous implant or daily injections from the day
      of transfer. The approach described in this study provides the opportunity to
      explore transgenic and chimeric models in the monkey by the development of
      noninvasive methods to transfer late-stage embryos that have been manipulated in
      vitro.

PMID- 11515671
TI  - Exposure to the dioxin 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces
      squamous metaplasia in the endocervix of cynomolgus macaques.
AB  - Female cynomolgus macaques (n = 11) were treated orally with graded doses of
      2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Cervical tissue was recovered at
      necropsy 1.2-2.7 years later and examined using routine histopathology. Results
      were compared histologically with cervical tissue from untreated, age- and parity
      matched controls. Significant squamous epithelial metaplasia was observed in the
      endocervix of 9 of 11 TCDD-treated animals, and the degree of severity was dose
      dependent. In contrast, minimal or no pathological changes were observed in eight
      of nine control animals and one animal had only mild squamous metaplasia. These
      results suggest that TCDD exposure induces epithelial transdifferentiation in the
      primate cervix. Consequently, the TCDD-treated macaque may serve as a predictable
      animal model for the study of cervical epithelial transdifferentiation and for
      examining the relationship between squamous metaplasia and cervical oncogenesis
      both at the cellular and at the molecular level.

PMID- 11515672
TI  - Changes in blood chemistry and hematology variables during aging in captive
      rhesus macaques (Macaca mulatta).
AB  - Identifying changes with age in physiological variables of captive nonhuman
      primates will aid in the proper treatment and clinical diagnosis of these
      animals, as well as enhance our understanding of nonhuman primate models for
      human aging. Information for 33 physiological variables was obtained from the
      Primate Aging Database, a multi-centered database being developed for clinical
      and research use. Using multiple regression analyses, we investigated the
      relationship of age to hematological variables, blood chemistry and body weight
      in 345 captive rhesus monkeys (age range 7-30 years) from three different primate
      research facilities. The analyses revealed that 15 of these variables show a
      significant relationship with chronological age and are altered in older as
      compared with adult animals. Here we present the first phase of a project that
      will: a) identify changes with age in physiological variables among adult captive
      rhesus macaques; and b) characterize normative values for the aging rhesus
      population.

PMID- 11515673
TI  - Age changes in plasma IGF-1 concentration in free-ranging Japanese macaques
      (Macaca fuscata).
AB  - To obtain fundamental data on the endocrine background for the wild Japanese
      macaque (Macaca fuscata) growth profiles, we have measured plasma insulin-like
      growth factor 1 (IGF-1) concentrations of free-ranging and open-enclosed Japanese
      macaques from five different regions in their habitat. General features of the
      IGF-1 levels in those troops were: 1) an age-dependent increase in the young
      macaques and 2) distinctively higher values among several adult females. The age
      changes in IGF-1 levels during the adolescent period in the free-ranging Japanese
      macaques were similar to those in the caged Japanese macaques.

PMID- 11515674
TI  - Callitrichid nutrition and food sensitivity.
AB  - Captive callitrichids are prone to developing intestinal problems. Their captive
      and natural diets differ enormously, and diet has been suggested to play a major
      role in wasting marmoset syndrome. Proteins in wheat, soy and milk are included
      in callitrichid diets of most colonies and have been linked to an immune reaction
      in Saguinus oedipus and Callithrix jacchus. In the present study of 23 males and
      females of the two species, wheat protein was tested but soy and milk products
      were excluded. One group had wheat and the other had rice in their diet. Blood
      samples and biopsies from the colon were taken. Results showed changes in the
      colon and an immune reaction to gliadin, a wheat protein related to coeliac
      disease in humans. A further immune reaction was also observed. Suggestions for
      further study and exclusion of cereal in the diet of these small, New World
      primates are discussed.

PMID- 11515675
TI  - Spontaneous Waterhouse-Friderichsen syndrome in a gang-housed baboon.
AB  - Waterhouse-Friderichsen syndrome can cause acute death in the baboon without
      specific signs. Furthermore, this syndrome could result from stress-related
      intestinal permeability changes that allow macromolecules and/or microbiological
      entities to enter the systemic circulation. The resulting sepsis could cause
      adrenocortical insufficiency, hypotension and shock leading to death.

PMID- 11515676
TI  - Dilated cardiomyopathy in monkeys--beware of Trypanosoma cruzi infection.

PMID- 11515677
TI  - Cytokine-activated degradation of inhibitory kappaB protein alpha is inhibited by
      the short-chain fatty acid butyrate.
AB  - Butyrate, a short-chain fatty acid, is generated by anaerobic fermentation within
      the colon. Clinical trials suggest that short-chain fatty acids ameliorate
      inflammation in ulcerative colitis. Nuclear factor (NF) kappaB, an inducible
      transcription factor that is activated in inflamed colonic tissue, is sequestered
      to the cytoplasm by its inhibitory IkappaB proteins. The anti-inflammatory
      effects of butyrate are associated with an inhibition of NF-kappaB nuclear
      translocation. To investigate the mechanism of NF-kappaB inhibition we examined
      the effects of butyrate on IkappaBalpha. Human adenocarcinoma cells (SW480,
      SW620, and HeLa229) were treated with butyrate for up to 48 h followed by tumor
      necrosis factor (TNF) alpha stimulation. NF-kappaB was detected by
      immunofluorescence staining with an antibody against its p65 subunit. Levels of
      IkappBalpha and phosphorylated IkappaBalpha were determined by western blot.
      Stimulation with TNFalpha resulted in rapid phosphorylation and degradation of
      IkappaBalpha followed by NF-kappaB nuclear translocation. Butyrate pretreatment
      successfully inhibited NF-kappaB activation. Pretreatment of adenocarcinoma cells
      with butyrate is associated with inhibition of TNFalpha-mediated phosphorylation
      and degradation of IkappaBalpha and effective blocking of NF-kappaB nuclear
      translocation. The anti-inflammatory effects of butyrate may at least in part be
      mediated by an inhibition of IkappaBalpha mediated activation of NF-kappaB.

PMID- 11515678
TI  - Helicobacter pylori infection, gastrin, cyclooxygenase-2, and apoptosis in
      colorectal cancer.
AB  - Helicobacter pylori (HP) infection is usually accompanied by an increased plasma
      level of gastrin, a potent mitogen able to induce cyclooxygenase (COX)-2. This
      study examined (a) the seroprevalence of HP, its cytotoxic protein, CagA, and
      cytokines (tumor necrosis factor alpha, interleukins 1beta and 8) in 80 patients
      with colorectal cancers, before and after the removal of tumor, compared with 160
      age- and gender-matched controls; (b) the gene expression of gastrin and its
      receptors (CCKB-R) in the cancer tissue, (c) the plasma levels and tumor tissue
      contents of gastrin, and (d) the mRNA expression of COX-1, COX-2, and apoptotic
      proteins (Bax and Bcl2) in cancer tissue and intact colonic mucosa. Anti-HP IgG,
      anti-CagA IgG seroprevalence, and cytokine levels were analyzed by enzyme-linked
      immunosorbent assay tests; gene expressions of gastrin, CCKB-R, COX-1, COX-2,
      Bax, and Bcl2 by reverse transcriptase polymerase chain reaction; and gastrin by
      radioimmunoassay. The seroprevalence of HP, especially that expressing CagA, was
      significantly higher in cancer patients than in controls and did not change 1
      week after tumor resection while plasma cytokines were significantly reduced
      after this operation. Both gastrin and CCKB-R mRNA were detected in the cancer
      tissue and the resection margin; similarly, COX-2 mRNA was expressed in most of
      cancers and their resection margin but not in intact colonic mucosa, where only
      COX-1 was detected. The colorectal cancer tissue contained several folds more
      immunoreactive gastrin than cancer resection margin and many folds more than the
      intact colonic mucosa. We conclude that colon adenocarcinoma and its resection
      margin overexpress gastrin, its receptors, CCKB-R, and COX-2, and that HP
      infection may contribute to colonic cancerogenesis via overexpression of gastrin
      and COX-2, which may account for the stimulation of the tumor growth and the
      reduction in apoptosis as documented by enhanced mRNA expression of anti
      apoptotic Bcl2 over proapoptotic Bax proteins.

PMID- 11515679
TI  - Fibromyalgia in patients with irritable bowel syndrome. An association with the
      severity of the intestinal disorder.
AB  - Fibromyalgia (FM) syndrome and irritable bowel syndrome (IBS) are functional
      disorders in which altered somatic and or visceral perception thresholds have
      been found. The aim of this study was to evaluate the prevalence of FM in a group
      of patients with IBS and the possible association of FM with patterns and
      severity of the intestinal disorder. One hundred thirty consecutive IBS patients
      were studied. The IBS was divided into four different patterns according to the
      predominant bowel symptom and into three levels of severity using a functional
      severity index. All patients underwent rheumatological evaluation for number of
      positive tender points, number of tender and swollen joints, markers of
      inflammation, and presence of headache and weakness. Moreover, patients'
      assessments of diffuse pain, mood and sleep disturbance, anxiety, and fatigue
      were also measured on a visual analogue scale. The diagnosis of FM was made based
      on American College of Rheumatology classification criteria. Nonparametric tests
      were used for statistical analysis. Fibromyalgia was found in 20% of IBS
      patients. No statistical association was found between the presence of FM and the
      type of IBS but a significant association was found between the presence of FM
      and severity of the intestinal disorder. The presence of FM in IBS patients seems
      to be associated only with the severity of IBS. This result confirms previous
      studies on the association between the two syndromes.

PMID- 11515680
TI  - Influence of laparoscopy and laparotomy on systemic and peritoneal T lymphocytes
      in a rat model.
AB  - Little is known about the local influence of pneumoperitoneum on components of
      the peritoneal immune defense mechanisms. We investigated CD25, CD4, CD8
      expression and CD4/CD8 ratio of systemic and peritoneal T lymphocytes in a rat
      model. Fifty male Sprague Dawley rats underwent laparotomy, CO2 pneumoperitoneum,
      helium pneumoperitoneum, gasless laparoscopy, or anesthesia only. After 24 h
      venous blood was drawn, and peritoneal lavage was performed to harvest CD25+,
      CD4+, and CD8+ cells. CD4+, CD8+, and CD25+ T lymphocytes were determined. A
      significantly lower peritoneal CD4/CD8 ratio was found after CO2 and helium
      laparoscopy than in controls (P<0.05). However, no significant differences in
      systemic CD4/CD8 ratio or peritoneal or systemic CD25 expression were found
      between the different operative groups. Pneumoperitomeum independently of the
      insufflation gas (CO2 or helium) leads to comparable postoperative
      immunmodulations of peritoneal CD4+ and CD8+ T-lymphocytes. The mechanical
      pressure of the pneumoperitoneum seems to aggravate peritoneal T lymphocytes.

PMID- 11515681
TI  - Stapled ileoanal pouches without loop ileostomy: a prospective study in 86
      patients.
AB  - In restorative proctocolectomy the use of a stapling technique to construct an
      ileal pouch with anal anastomosis offers an alternative to the hand-sewn
      technique following mucosectomy; a temporary defunctioning loop ileostomy may
      reduce the consequences of an anastomotic leakage, however it may entail
      discomfort for the patient, an additional operation, possible complications, and
      longer total hospital stay. This prospective study evaluated the peri- and
      postoperative courses in 86 consecutive, referred patients receiving ileal pouch
      anal anastomosis using the stapling technique to construct the ileal pouch and
      ileoanal anastomosis, omitting the defunctioning loop ileostomy except in cases
      of increased risk of ileoanal anastomotic insufficiency according to defined
      criteria. Follow-up time was 36-96 months. Patients undergoing primary loop
      ileostomy stayed a median of 19 days in hospital, as opposed to a median of 9
      days in those who did not. Eight patients developed pelvic sepsis that demanded a
      secondary defunctioning loop ileostomy, and five showed symptoms arising from
      relapsing inflammation in residual rectal mucosa; in three of these, a secondary
      transanal mucosectomy covered by a loop ileostomy was necessary. During the
      follow-up period ten patients had bowel obstructions that demanded surgery; two
      developed late pouch-vaginal fistulas, and one a fistula from the J-limb to the
      abdominal scar. There was one case of pouch procidentia. At 12-month follow-up
      the median evacuation frequency was 6 per 24 h, the incidence of minor
      incontinence was about 10%, and urgency to evacuate occurred in about 10%. None
      of the patients experienced any major incontinence. The stapling technique and
      omission of the defunctioning loop ileostomy in restorative proctocolectomy were
      thus a comparatively reliable and time-saving method with short total hospital
      stay. In patients at increased risk of anastomotic complications, however, a
      defunctioning loop ileostomy is recommended. We believe it is important to
      perform an exact dissection into the anal canal to avoid a residual rectal mucosa
      that may be inflamed or even become dysplastic.

PMID- 11515682
TI  - Solitary rectal ulcer syndrome: a series of 13 patients operated with a mean
      follow-up of 4.5 years.
AB  - Solitary rectal ulcer syndrome (SRUS) is an infrequent pathology often associated
      with pelvic floor disorders. The aim of this retrospective study was to review
      the long-term results of a surgical series of SRUS. Between 1988 and 1998, 13
      patients were operated on for SRUS. Seven patients had associated internal rectal
      prolapse (58%), two had associated total rectal prolapse (15%), and two had
      associated mucosal prolapse (15%). We performed simple resection of the SRUS in
      one case (8%), a stoma as primary operation in one (8%), three rectopexies
      according to Orr-Loygue (23%), and eight Delorme's operations as modified by
      Berman (62%). Mean follow-up was 57 months (range 15-112). Simple resection of
      the solitary rectal ulcer syndrome did not improve symptoms. Colostomy permitted
      relief of symptoms and healing of the SRUS. Two of the three rectopexies achieved
      good results, and the third patient relapsed at the 6th postoperative month. A
      secondary modified Delorme's operation permitted relief of symptoms and healing
      of the SRUS. Five of the eight patients (62.5%) who received modified Delorme's
      operations had improved at a follow-up of 46 months. We conclude that,
      considering the high failure rate after surgery, operations should be performed
      only in patients with total rectal prolapse or intractable symptoms not amenable
      to behavioral therapy. Delorme's operation and abdominal rectopexy help in about
      60% of cases.

PMID- 11515683
TI  - Ultralow anterior resection and coloanal anastomosis for distal rectal cancer:
      functional and oncological results.
AB  - We evaluated the functional and oncological outcome of ultralow anterior
      resection and coloanal anastomosis (CAA), which is a popular technique for
      preserving anal sphincter in patients with distal rectal cancer. Forty-eight
      patients were followed up for 6-100 months regarding fecal or gas incontinence,
      frequency of bowel movement, and local or systemic recurrence. The main operative
      techniques were total mesorectal excision with autonomic nerve preservation; the
      type of anastomosis was straight CAA, performed by the perianal hand sewn method
      in 38 cases and by the double-stapled method in 10. Postoperative complications
      included transient urinary retention (n=7), anastomotic stenosis (n=3),
      anastomotic leakage (n=3), rectovaginal fistula (n=2), and cancer positive margin
      (n=1; patient refused reoperation). Overall there were recurrences in seven
      patients (14.5%): one local and one systemic recurrence in stage B2; and one
      local, two systemic, and two combined local and systemic in C2. The mean
      frequency of bowel movements was 6.1 per day after 3 months, 4.4 after 1 year,
      and 3.1 after 2 years. The Kirwan grade for fecal incontinence was 2.7 after 3
      months, 1.8 after 1 year, and 1.5 after 2 years. With careful selection of
      patients and good operative technique, CAA can be performed safely in distal
      rectal cancer. Normal continence and acceptable frequency of bowel movements can
      be obtained within 1 year after operation without compromising the rate of local
      recurrence.

PMID- 11515684
TI  - Clinical and histopathological features of dextran sulfate sodium induced acute
      and chronic colitis associated with dysplasia in rats.
AB  - We examined the clinical and histopathological features of the dextran sulfate
      sodium (DSS) induced acute and chronic colitis in rats as a model for studying
      basic biology of the inflamed colonic mucosa. Acute colitis was induced in male
      Wistar rats by 4 days (AI) or 7 days (AII) of oral 5% (wt/vol) DSS (mol. wt.
      54,000) in their drinking water. Chronic colitis was induced in 8 experimental
      groups: CI=7 days DSS followed by 10 days water (=one cycle); CII=two cycles;
      CIII to CVIII (three to eight cycles) received only 4 days 5% DSS followed by 10
      days drinking water. The entire colons were examined histologically; dysplasia
      was graded as: indefinite/probably negative for dysplasia, indefinite/probably
      positive for dysplasia, low-grade dysplasia, or high-grade dysplasia. The
      earliest clinical findings in the acute colitis group over 4 days occurred on day
      2 (hemoccult positive stools, loose stools or diarrhea and weight loss). The
      maximal disease activity was noted on day 7 accompanied by a 53% mortality rate.
      The histological inflammation scores were significantly higher on day 7 than on
      day 4. All rats had extensive ulcerations predominantly in the rectum and cecum.
      The number of rats having ulcerations was markedly lower in the chronic colitis
      groups. The majority (75%) of the crypt lesions suspicious for dysplasia were
      classified as mucosa indefinite/probably negative for dysplasia. We classified 18
      crypt lesions as low-grade dysplasia and one lesion as high-grade dysplasia
      (after eight cycles). No invasive carcinoma was observed. Most low-grade
      dysplasias (83%) occurred after five cycles of DSS/water, located mostly in the
      rectum (44%) and colon transversum (33%). Our findings suggest that the DSS
      colitis model in rats may be an interesting model for studying the sequence
      chronic inflammation-dysplasia in human ulcerative colitis. Further long-term
      studies with the present DSS colitis model in rats might also prove it as a
      reliable model to study the sequence high-grade dysplasia and colitis associated
      cancer.

PMID- 11515685
TI  - Dynamic contrast-enhanced power Doppler sonography improves the differential
      diagnosis of liver lesions.
AB  - The aim of this paper was to investigate the diagnostic value of dynamic contrast
      enhanced power Doppler sonography in the differential diagnosis of liver lesions.
      We prospectively examined 85 focal liver lesions in 71 patients by real-time gray
      scale sonography, power Doppler sonography, and contrast-enhanced power Doppler
      using two ultrasound contrast agents (Levovist, Optison). Amount and architecture
      of lesion vascularity and the kinetics of contrast enhancement within the lesions
      were analyzed. Vascularity was detected in 61% of liver lesions (52/85) by
      conventional power Doppler, compared to 86% (73/85) by contrast-enhanced power
      Doppler sonography. Dynamic contrast-enhanced power Doppler identified arterial
      radial hypervascularity <16 s after contrast injection in 19/22 focal nodular
      hyperplasias (86%). Irregular hypervascularity was seen with contrast enhancement
      in the arterial phase in 14/15 hepatocellular carcinomas (93%). In 14/25
      hemangiomas (56%), a circular vascularization pattern was noted. Specific lesion
      diagnosis based on B-scan and conventional and dynamic contrast-enhanced power
      Doppler sonography led to correct diagnosis in 86% (73/85, 95% confidence
      interval 78%-94%) compared to 57% (48/85, 95% confidence interval 47%-94%) by B
      scan criteria and conventional power Doppler sonography. Contrast-enhanced power
      Doppler sonography improves diagnostic accuracy in the differential diagnosis of
      focal liver lesions.

PMID- 11515686
TI  - Prevalence of polyps and diverticulosis of the large bowel in the Cretan
      population. An autopsy study.
AB  - While a number of studies have been performed in the United States, northern
      Europe, and some other countries on the epidemiology of large bowel polyps and
      diverticulosis, information from southern Europe and especially Greece is very
      limited. Our autopsy study sought to determine the prevalence of large bowel
      polyps and diverticulosis in the population on Crete. Specimens of colon and
      rectum were obtained during forensic postmortem autopsies and examined for the
      presence of polypoid lesions and diverticulosis. Data were collected from a total
      of 502 autopsies (320 men, 182 women; median age 65 years (range 16-93). Polyps
      were found in 106 cases (21.1%). These were adenomas in 73 cases (14.5%),
      hyperplastic polyps in 25 (4.9%), and mucosal tags in 8 (1.5%). Diverticulosis of
      the large bowel was found in 115 (22.9%). The prevalence of adenomas and
      diverticulosis increased with advanced age. The prevalence of colonic
      diverticulosis in Crete is slightly lower than that which has been reported in
      most other studies in economically developed countries. The prevalence of
      colorectal adenomas in Crete is one of the lowest rates reported in Europe and is
      compatible to the known low incidence of colorectal cancer in Crete.

PMID- 11515687
TI  - Early colonic carcinoma with extensive lymph node metastases: case report and
      review of literature.
AB  - An 81-year-old woman had an early carcinoma invading focally into the upper
      submucosa of the middle-transverse colon, which was accompanied by extensive
      lymph node metastases and resulted in a poor prognosis. Although her tumor was
      small and flat, a rim of pale yellow-speckled mucosa adjacent to the tumor
      enabled its earlier detection. To further study the exceptional lymph node
      metastases we studied the expression of intestinal trefoil factor and sialyl Tn
      antigen immunohistochemically on the resected specimen. Their simultaneous
      expression in lymph node metastasis further supports the aggressive nature of
      this tumor.

PMID- 11515688
TI  - Mental stress and its importance for cardiovascular disorders; physiological
      aspects, "from-mice-to-man".

PMID- 11515689
TI  - Heart and soul: stress and the metabolic syndrome.

PMID- 11515690
TI  - Perinatal origin of adult disease.

PMID- 11515691
TI  - Recovery of autonomic nervous activity after myocardial infarction demonstrated
      by short-term measurements of SDNN.
AB  - OBJECTIVE: Heart rate variability (HRV) has been demonstrated to be a risk factor
      after acute myocardial infarction (AMI). In the present study serial measurement
      of SDNN (standard deviation of the mean of qualified NN-interval) in short
      intervals was used to assess HRV changes after AMI, and determine the role of
      these as independent risk factors compared to clinical, arrhythmic, ischemic and
      anamnestic variables. Measurements from a normal healthy middle-aged male
      population were used as reference (n = 63). METHODS: SDNN from a five-minute
      period during day and night-time, respectively, was examined in 103 patients 1
      week (n = 54), 1 month (n = 72) and 12-16 months (n = 54) after infarction.
      RESULTS: Day SDNN did not change during one-and-a-half years after AMI, and was
      significantly reduced compared with healthy males. Night SDNN, low after 1 week,
      with recovery 1 month after AMI, was significantly reduced compared with healthy
      males early, but not late after AMI. Thus, the study indicated during day-time a
      continuous abnormal sympathetic preponderance in the course of 16 months after
      AMI, and during night-time a gradual recovery of parasympathetic preponderance
      beginning early after AMI. CONCLUSION: One week after AMI day-time SDNN of <30
      ms, and night-time SDNN of < 18 ms, age > or =60 years, and myocardial ischemia
      (Holter monitoring) were independent predictors of 9 years' mortality. One and 12
      16 months after AMI reduced day and night-time SDNN had no prognostic
      implication.

PMID- 11515692
TI  - The outcome of children born with pulmonary atresia and intact ventricular septum
      in Sweden from 1980 to 1999.
AB  - OBJECTIVE: To study the outcome of all children born with pulmonary atresia and
      intact ventricular septum in Sweden between 1980 and 1999. DESIGN: Retrospective
      study of medical records with review of the initial, preoperative
      angiocardiographic and echocardiographic examinations. RESULTS: A total of 84
      children were born with pulmonary atresia and intact ventricular septum, giving
      an incidence of 4.2 per 100,000 live births. In all, 77 were operated on with a 1
      year survival rate of 75%. Thirty-six children had ventriculocoronary
      communications, with a 1-year survival rate of 50%. At the end of the study
      period, 52 children were alive, 32 with biventricular repair, and 19 with
      univentricular repair. Follow-up time was 14 days-20 years (median, 6 years).
      Statistical analysis of incremental risk factors for death showed statistical
      significance for low birth weight, male sex, muscular pulmonary atresia, and
      having a systemic-to-pulmonary shunt as the sole initial intervention.
      CONCLUSION: Complete national data of all patients born with pulmonary atresia
      and intact ventricular septum during 1980-1999 in Sweden revealed a total
      mortality in accordance with previous reports for results for surgery. Further
      improvements demand a thorough preoperative investigation of the cardiac anatomy,
      particularly of the ventriculocoronary communications, to enable right
      ventricular decompression whenever possible.

PMID- 11515693
TI  - Transseptal catheterization without needle puncture.
AB  - OBJECTIVE: The aim was to see if probing the fossa ovalis for transseptal
      puncture during balloon mitral valvuloplasty will reduce time consumed for the
      procedure. DESIGN: Twenty-five patients had probing of fossa ovalis for left
      atrial entry (group I). In 30 patients (group II), standard needle puncture was
      done for left atrial entry. Puncture time and fluoroscopy time were noted and
      oxymetry was done. Later, a further 60 patients underwent probing of fossa ovalis
      for validation of the technique. RESULTS: Puncture times in groups I and II were
      84.7 +/- 27.5 and 116.1 +/- 37.9 s, respectively (p < 0.02). Fluoroscopy time was
      51.2 +/- 19.6 and 73.6 +/- 22.3 s in groups I and II, respectively (p < 0.03).
      During validation of the technique, 54 of 60 patients (90%) had successful left
      atrial entry through probing. Atrial level shunt was not seen. CONCLUSION:
      Probing the fossa achieves left atrial entry in 90% of patients. It avoids needle
      puncture and reduces puncture time as well as fluoroscopy time. It is a safe
      technique.

PMID- 11515694
TI  - Clinical variables and pro-inflammatory activation in paediatric heart surgery.
AB  - OBJECTIVES: The first aim was to analyse the role of preoperative characteristics
      and perioperative variables in predicting the inflammatory response during and
      early after operations for congenital heart malformations of moderate to severe
      complexity. The second aim was to correlate complement and cytokine activation
      during the same period with clinical variables reflecting the postoperative
      course. METHODS: Prospective descriptive clinical study that involved 22
      consecutive children (1-28 months). Five children had Down's syndrome.
      Concentrations of C3a, C5b-9 and IL-6 were measured. RESULTS: C3a, C5b-9 and IL-6
      increased significantly during the study period (ANOVA: C3a, p = 0.001; C5b-9, p
      = 0; IL-6, p = 0). C3a correlated with preoperative haemoglobin (r = 0.71, p =
      0.0002) and CPB time (r = 0.72, p=0.0005). C5b-9 correlated with CPB time (r=
      0.58, p=0.004). IL-6 related to presence of Down's syndrome (p=0.0001) and
      correlated with preoperative haemoglobin (r=0.55, p=0.02), preoperative weight
      deviation (r = -0.52, p = 0.03) and time in the ventilator (r = 0.68, p = 0.002).
      CONCLUSIONS: Preoperative and perioperative characteristics predict the
      inflammatory response during open heart surgery in infants and small children. IL
      6 response is related to the postoperative course.

PMID- 11515695
TI  - Myocardial uptake and release of substrates in type II diabetics undergoing
      coronary surgery.
AB  - OBJECTIVE: Knowledge about myocardial metabolism in diabetic patients is limited,
      and even more so in association with myocardial ischaemia and cardiac surgery.
      This study investigates myocardial substrate utilization in type II diabetic
      patients after elective coronary artery bypass graft surgery (CABG). DESIGN:
      Myocardial substrate utilization in 10 type II diabetic patients was assessed
      during the first hours after elective CABG with the coronary sinus catheter
      technique. RESULTS: No significant myocardial uptake of carbohydrates was
      observed. Free fatty acids were extracted throughout the study period but uptake
      was not related to arterial levels. As arterial levels of beta-hydroxybutyric
      acid tended to increase a significant myocardial uptake emerged. The average
      extraction rate of beta-hydroxybutyric acid was 31% with a peak of 42%. A
      comparable extraction rate of glutamate was also found whereas alanine was
      released from the heart. CONCLUSION: Free fatty acids were the main source of
      energy for the heart whereas uptake of carbohydrates was restricted. The high
      extraction rates of beta-hydroxybutyric acid and glutamate suggest an adaptive
      role for these substrates during this unfavourable metabolic state for the post
      ischaemic diabetic heart.

PMID- 11515696
TI  - Bronchial arterial devascularization. An experimental study in pigs.
AB  - OBJECTIVE: The lungs have dual blood supply: The bronchial and the pulmonary
      circulation. The importance of bronchial circulation is disputed. The purpose of
      this study was to establish an experimental model to examine the importance of
      the bronchial artery. DESIGN: Comparative porcine experimental study. The
      surgical technique was evaluated in group A (n = 9). Group B (n = 8) underwent
      left bronchial arterial devascularization. In group C (n = 9) the left principal
      bronchus was devascularized, transsected, and reanastomosed. In groups B and C
      bronchial mucosal blood flow was studied with laser-Doppler velocimetry.
      Devascularization was controlled by angiography at section, and specimens were
      examined with conventional histology and scanning electron microscopy. The right
      bronchus served as control. RESULTS: In group B devascularization caused
      considerable, yet insignificant reduction in bronchial mucosal blood flow index
      (p = 0.1282) postoperatively, and after 1 week (p = 0.0678), insignificant
      histologic (p > 0.2) changes, and no scanning electron microscopy differences. In
      group C devascularization with bronchial transsection caused significant
      reduction in mucosal blood flow index (p = 0.0277) postoperatively and after 1
      week (p = 0.0277), significant histologic changes (p = 0.0277), and insignificant
      (p = 0.069) changes in scanning electron microscopy. CONCLUSION: Bronchial
      arterial devascularization with transsection caused significant physiologic and
      morphologic changes, and a model with bronchial devascularization should include
      transsection.

PMID- 11515697
TI  - Mitral valve incompetence following blunt chest trauma after mitral valve repair.
      Recognition by three-dimensional echocardiography.
AB  - We present a unique case of mitral incompetence following blunt chest trauma in a
      46-year-old woman who had undergone successful mitral valve repair 2 years before
      the accident. Three-dimensional echocardiography revealed the precise pathology,
      with partial avulsion of the annuloplasty ring and rupture of chordae tendineae.

PMID- 11515698
TI  - Successfully treated composite graft infection after Bentall's procedure.
AB  - A 47-year-old male patient underwent Bentall's modification with total arch
      replacement owing to type A acute dissection. Mediastinitis and composite graft
      infection occurred 3 weeks after the operation. Extensive debridement and
      irrigation followed by omental wrapping without graft removal were performed and
      the patient was successfully cured.

PMID- 11515699
TI  - The relationship between cannabis use, depression and anxiety among Australian
      adults: findings from the National Survey of Mental Health and Well-Being.
AB  - BACKGROUND: This study aimed to examine the patterns of association between
      cannabis use, and anxiety and affective disorders, in the general population.
      METHOD: Data from the Australian National Survey of Mental Health and Well-Being,
      a representative survey of Australians aged 18 years and over, were analysed to
      address the following questions: (1) is there an association between cannabis
      use, DSM-IV abuse and dependence, and DSM-IV affective and anxiety disorders; (2)
      if so, is it explained by: demographic characteristics, levels of neuroticism, or
      other drug use; and (3) does the presence of a comorbid affective or anxiety
      disorder affect the likelihood of treatment seeking among cannabis users?
      RESULTS: There was a moderate univariate association between involvement with
      cannabis use in the past 12 months and the prevalence of affective and anxiety
      disorders. Among those with DSM-IV cannabis dependence, 14% met criteria for an
      affective disorder, compared to 6% of non-users; while 17% met criteria for an
      anxiety disorder, compared to 5% of non-users. These associations did not remain
      significant after including demographics, neuroticism and other drug use in
      multiple regressions. CONCLUSIONS: Cannabis use did not appear to be directly
      related to depression or anxiety when account was taken of other drug use.
      However, the association between heavier involvement with cannabis use and
      affective and anxiety disorders has implications for the treatment of persons
      with problematic cannabis use.

PMID- 11515701
TI  - Anxiety and the schizophrenic process: clinical and epidemiological evidence.
AB  - BACKGROUND: The authors hypothesise that anxiety is an integral part of the
      development of schizophrenia in a significant sub-group of cases. This paper
      reviews the evidence for an epidemiological link between anxiety and
      schizophrenia, emphasising those studies that imply a temporal sequence. METHOD:
      An augmented systematic search of electronic databases was conducted, and the
      methods and results of the studies identified were reviewed. RESULTS: Panic
      disorder was identified in around 20% of cases of schizophrenia in clinical
      studies (range 5-33 %). Other anxiety disorders were less often studied, but were
      also frequent. Epidemiological studies from the Epidemiological Catchment Area
      Program confirm the strong association between anxiety disorders and
      schizophrenia. Finally, cohort studies identify anxiety as an early antecedent of
      schizophrenia. CONCLUSION: There is a significant link between anxiety and
      schizophrenia. This may represent a psychological process integral to an
      appreciable number of cases of schizophrenia. Focused psychological studies are
      needed to determine whether this is so.

PMID- 11515700
TI  - Substances used in deliberate self-poisoning 1985-1997: trends and associations
      with age, gender, repetition and suicide intent.
AB  - BACKGROUND: Rates of deliberate self-poisoning have increased in recent years.
      While over-the-counter availability and prescribing patterns may influence trends
      in substances used in overdose, these may also be related to clinical
      characteristics of patients. We investigate trends in substances used for self
      poisoning and the influence of age, gender, suicidal intent and repetition status
      on the substances used. METHOD: Data collected by the Oxford Monitoring System
      for Attempted Suicide were used to review trends and patterns of self-poisoning
      between 1985 and 1997. RESULTS: There were substantial increases in self
      poisoning with paracetamol and antidepressants. While the increase in
      antidepressant self-poisoning closely paralleled local prescribing figures during
      1995-97, SSRI antidepressant overdoses occurred somewhat more often than expected
      compared with tricyclic overdoses. Paracetamol overdoses were more common in
      first-timers and young people, whereas overdoses of antidepressants and
      tranquillizers were more common in repeaters and older people. Self-poisoning
      with gas and non-ingestible poisons was associated with high suicidal intent.
      CONCLUSIONS: There have been marked changes in the substances used for self
      poisoning, which seem primarily to reflect availability, as do the influences of
      age and repeater status on choice of substances used. Degree of suicidal intent
      may also influence choice of method of self-poisoning.

PMID- 11515702
TI  - Outcome assessment in psychiatric service evaluation.
AB  - BACKGROUND: The present paper gives an overview of outcome assessment issues in
      psychiatric service evaluation, based on seven proposals concerning the content
      and methodology of outcome assessment. It is stressed that outcome assessments
      should be performed on both the system and the patient level and that multiple
      outcome domains should be used, reflecting multiple perspectives of the services.
      It is also argued that outcome studies benefit from incorporating service use
      measures in order to enable analyses of costs and cost-effectiveness of services.
      Outcome studies of community-based psychiatric services have so far mainly
      investigated service models or programs. CONCLUSIONS: It is concluded that there
      is a need to investigate the relationship between particular parts and content of
      services and outcome, in order to increase knowledge of what is effective in
      community-based psychiatric services.

PMID- 11515703
TI  - Quality of life outcome in a randomized controlled trial of case management.
AB  - BACKGROUND: This paper presents the quality of life (QOL) outcome results from
      the UK700 randomised controlled trial of case management. METHOD: A total of 708
      patients with severe mental illness were randomly assigned to intensive and
      standard forms of case management in four sites in the UK. QOL was assessed using
      the Lancashire Quality of Life Profile, which provides a self-reported objective
      and subjective appraisal of eight life domains (finances, work, leisure, family,
      social relations, living situation, safety and health). The outcome after 2 years
      was examined using univariate and multivariate analyses. RESULTS: Significant
      improvements in QOL over the 2 years were observed. The QOL outcome did not
      differ significantly by case management treatment conditions or by diagnosis. A
      better outcome was associated with improvements in depression and with the
      location (site) of treatment. In one site there were significant improvements in
      all eight domains and overall QOL, with moderate or better effect sizes (> 0.4)
      in three domains and overall QOL. CONCLUSIONS: Depression should be assessed when
      subjective QOL measures are used. Better means for describing service
      organisations and the context/place in which they operate should be developed in
      order to explain more of the variance in QOL outcomes.

PMID- 11515704
TI  - Restructuring mental health: a South American survey.
AB  - BACKGROUND: There is little information available on the changes in mental health
      services in South American countries following the social and political upheavals
      of recent decades. METHODS: A postal survey was conducted of all South American
      countries (health ministries, national psychiatric associations and key
      informants) to assess the development of mental health programs and the
      organization of alternative psychiatric care centers such as the psychiatric
      units in general hospitals (PUGH). RESULTS: Most of the mental health programs
      were implemented during the 1980s and 1990s, and aimed at incorporating
      psychiatric care into primary health care, as well as relocating provision from
      large hospitals to decentralized services. Most of the countries surveyed have
      less than 0.5 psychiatric beds per 1000 inhabitants. This change reflects a
      tendency to reduce the total number of psychiatric beds and increase the number
      of PUGH. Over the last 10 years this increase was significant in some countries
      (50-75%), but was not reflected in the availability of adequate human and
      material resources. CONCLUSIONS: A transition from a system based on large mental
      hospitals to alternative service provision is on the way in South American
      countries. Intensive efforts have to be made to collect and disseminate
      information, as well as to monitor the development and outcome of the mental
      health programs in these countries.

PMID- 11515705
TI  - Persuading the persuadable: evaluating compulsory treatment in England using
      Supervised Discharge Orders.
AB  - BACKGROUND: Supervised Discharge Orders (SDOs) were introduced in 1995, as an
      amendment to the Mental Health Act in England and Wales. They require patients to
      abide by specific conditions on discharge from hospital, but can not enforce
      medication compliance. On introduction, SDOs were received with scepticism by the
      psychiatric profession. The purpose of this study was to describe the use of SDOs
      in England and the characteristics of patients made subject to these orders, and
      to evaluate the effectiveness of the order in securing treatment compliance on
      discharge from hospital. METHOD: A survey was conducted of 170 mental health
      provider Trusts in England. Interviews with senior managers in 12 Trusts and
      associated Local Authorities were subjected to qualitative analysis, and a cohort
      of patients subject to SDOs in 56 randomly sampled Trusts was described. RESULTS:
      SDOs were being used for 596 patients (1.2 per 100,000 total population) at the
      survey date in 1999, and use had been increasing steadily since its introduction.
      The order is not systematically considered for all potential cases. The majority
      of the 182 patients in the cohort had complied, if sometimes intermittently, with
      conditions of the order. CONCLUSIONS: For patients compliant with SDOs, the
      pressures necessary to treat effectively need not involve powers to enforce
      medication compliance.

PMID- 11515706
TI  - Semipersonalized psychological evaluation of quality of life in hypertensive
      patients during a trial with two calcium antagonists: a multicenter Latin
      American Study (LASTLHY).
AB  - OBJECTIVE: The main objective of this study was to evaluate well-being and
      physical activity of 248 hypertensive patients, including 177 females, who had
      previously been included in the Latin-American Study on Lacidipine in
      Hypertension (LASTLHY). SUBJECTS, MATERIALS AND METHODS: This open study was
      carried out in 12 clinical centers in Argentina, Brazil, Colombia, Mexico and
      Venezuela, to compare, over a period of 16 weeks, the antihypertensive action of
      a fixed-dose, once daily of 4 mg lacidipine administered orally to 120 patients
      and 30 mg nifedipine GITS (Gastro-Intestinal Therapeutic System) administered to
      128 patients, aged between 40 and 65 years. All patients had mild to moderate
      hypertension and treatment was begun at the end of a one-week placebo run-in
      period (end of week -1). Well-being and physical activity were assessed by means
      of single questionnaire, which reflected the physical and cultural diversities
      amongst the clinical centers and patients. The questionnaire included 13 multiple
      choice and 8 contingent open questions. The score of each question was multiplied
      by a coefficient related to the importance of each question to the patient
      (semipersonalization); the coefficient was obtained from cultural and
      socioeconomic data collected at the time of enrollment. The semipersonalization
      was carried out by a blind psychological study with respect to the medication and
      had a high repeatability in the assignment of personalized coefficients to the
      score of each question. The scores of each question were added to obtain an
      overall well-being and activity scoring. The possible theoretical range for the
      overall scoring in this study was 10 - 124. RESULTS: See Table 1. CONCLUSION: The
      study revealed that the administration of calcium channel blockers such as
      lacidipine and nifedipine GITS, and lacidipine in particular, produced low
      incidence of side effects, and lacidipine in particular induced significant
      improvement in the quality of life.

PMID- 11515707
TI  - Blood pressure reduction and tolerability of amlodipine versus nifedipine retard
      in Chinese patients with type 2 diabetes mellitus and hypertension: a randomized
      1-year clinical trial.
AB  - OBJECTIVE: In this 1-year clinical study, we compared the efficacy and
      tolerability of amlodipine and nifedipine retard in 64 Chinese Type 2 diabetic
      patients with hypertension. SUBJECTS AND METHODS: There were 25 (39.1%) men and
      39 (60.9%) women with mean age 60.7+/-9.9 years. Thirty-four patients were
      randomized to receive amlodipine 5 mg daily and 30 to receive nifedipine retard
      20 mg twice daily. The daily dose of amlodipine and nifedipine retard was
      increased from 5 mg to 10 mg daily and 20 mg to 40 mg twice daily, respectively,
      if sitting BP > 140/90 mmHg. RESULTS: Of the 64 patients, 9 dropped out early
      because they experienced adverse effects related to the drugs. If all treatment
      related adverse effects were taken into account, 6 (19.4%) patients were from the
      amlodipine group and 14 (53.8%) from the nifedipine group (p = 0.011). After 1
      year, 48 patients finished the study, 28 were on amlodipine and 20 were on
      nifedipine retard. Of the 28 patients from the amlodipine group, 11 (39.3%)
      required additional antihypertensive agents. Of the 20 patients from the
      nifedipine group, 5 (25%, p value: NS, comparing the 2 groups) required
      additional antihypertensive agents. Both groups showed similar and significant
      reduction in blood pressure from Week 6 to Week 52. CONCLUSION: Both amlodipine
      and nifedipine retard are relatively safe and useful in the treatment of
      hypertension in Chinese Type 2 diabetic patients. Nifedipine retard, when
      compared to amlodipine, showed significantly more adverse effects and these may
      hamper long-term compliance.

PMID- 11515709
TI  - Chemical instability and methods for measurement of cisplatin adducts formed by
      interactions with cysteine and glutathione.
AB  - Reactions between cisplatin or its aquated species and L-cysteine (L-cys) or
      glutathione (GSH) were studied in vitro using liquid chromatography on-line with
      inductively coupled plasma mass spectrometry (LC-ICPMS) and/or electrospray
      ionization mass spectrometry (LC-MS) in order to obtain information on the
      mechanisms occurring in treated patients. Reaction between cisplatin and L-cys
      yielded initially 4 adducts of which only 2 were stable and detectable after 24
      hours incubation; their structures corresponded to bis-platinum cysteinyl
      adducts. Reaction of cisplatin with GSH proceeded via the formation of at least
      11 glutathione-platinum adducts (G1 - G11) which underwent parallel reactions
      within 24 hours of incubation, probably to form higher molecular weight species.
      Of the 11 adducts, only 2, G3 and G7, whose structures correspond to
      [Pt(NH3)2Cl]2(SG) and [Pt(NH3)2OH]2(SG) were still present in the reaction
      mixture after 24 hours incubation. This study shows that GSH, and to a lesser
      extent L-cys, incubated with cisplatin in vitro forms unstable and reactive
      platinum compounds and that LC-ICPMS and LC-MS are 2 complementary techniques
      suitable for the study of organometallic compounds.

PMID- 11515708
TI  - Adverse drug reaction monitoring--digitoxin overdosage in the elderly.
AB  - Drug-related illness is an everlasting universal problem and also an important
      cause of admissions to hospitals. Adverse reactions are still grossly
      underreported by medical professions. Little information is available regarding
      the frequency or type of ADRs managed in hospitals. Since January 1997, we have
      taken part in a study, supported by the German Federal Institute for Drugs and
      Medical Device to improve the spontaneous drug information reporting system in
      Germany. Three German regionalized Departments of Clinical Pharmacology--Jena,
      Dresden, Rostock--serve as Pharmacovigilance Centers in collaboration with the
      Pharmacoepidemiology Research Group of the University of Munich. Since January
      1997, the regional group in Jena has been monitoring the University Clinic of
      Internal Medicine for admissions caused by adverse drug reactions. All emergency
      cases and patients on intensive care units were checked for adverse drug
      reactions. We present our results, including clinical and demographic data,
      concerning intoxications and especially those involving digitoxin in 210 patients
      with ADR. Forty patients with digitoxin toxicity had an average age of 81 years
      (81.1+/-6.3), a low body weight (59.7+/-12.7 kg) and 3 out of 4 were women. 75%
      of all patients with digitoxin side effects had elevated serum digitoxin levels
      with concentrations higher than 25 microg/ml. The relatively high frequency of
      digitoxin intoxications in our hospital may reflect the advanced age and low body
      weight of patients. Patients received digitoxin regardless of age, weight and,
      sometimes, clinical indication. Physicians should be aware of drugs having a high
      risk when used in elderly patients. The use of digitoxin assays and keeping serum
      levels within or near the therapeutic range will diminish the incidence of
      overdoses.

PMID- 11515710
TI  - Limits of 80%-125% for AUC and 70%-143% for Cmax. What is the impact on
      bioequivalence studies?
AB  - OBJECTIVE: The US Food and Drug Administration (FDA) currently uses
      bioequivalence (BE) limits for fasting BE studies that are based on the 90%
      confidence interval for the ratio of difference of the test and reference
      products Cmax and AUC falling within 80% to 125%. The FDA has also proposed that
      BE limits be used similarly for AUC and Cmax measurements from fed BE studies. In
      some cases, regulatory agencies have considered a wider BE limit for Cmax,
      because of the typically higher variability of Cmax compared to AUC. We
      investigated the consequences of changing from an 80%/ 125% limit for both
      pharmacokinetic measures to one that uses a limit of 80%/125% for AUC and
      70%/143% for Cmax. METHODS: We computed the sample sizes required for BE studies
      using 80%/125% for AUC and 70%/143% for Cmax as BE limits. We also determined the
      range of the ratios of Cmax and AUC values in a study that could meet the
      70%/143% and 80%/125% BE limits. RESULTS: The sample size for the study, in order
      to have adequate power with 80%/125% for AUC and 70%/143% for Cmax, will be
      determined primarily by the intrasubject variability of AUC, though with a
      substantial proportion of studies (about one third) still determined by the
      variability of Cmax. The ratio of mean Cmax values that can pass a wider 70%/143%
      BE limit could easily be as high as 128%. CONCLUSION: Without further scientific
      or clinical rationale, we find it difficult to justify widening the
      bioequivalence limit for Cmax to 70%/143% for either fasting or fed BE studies.

PMID- 11515711
TI  - Bioequivalence of clarithromycin tablet formulations assessed in Korean males.
AB  - AIM: Determination of the bioequivalence of 2 clarithromycin tablet formulations
      manufactured in Korea. PATIENTS AND METHODS: Twenty-four healthy male Korean
      volunteers received each of the 2 clarithromycin formulations at a dose of 250 mg
      in a 2 x 2 crossover study. There was a one-week washout period between doses.
      Plasma concentrations of clarithromycin were monitored by high-performance liquid
      chromatography over a period of 12 hours after administration. AUCinf (the area
      under the plasma concentration-time curve from time zero to time infinity) was
      calculated using the linear-log trapezoidal method. Cmax (maximum plasma drug
      concentration) and Tmax (time to reach Cmax) were compiled from the plasma
      concentration-time data. Analysis of variance was carried out using
      logarithmically transformed AUCinf and Cmax and untransformed Tmax. RESULTS: The
      point estimates and 90% confidence intervals for AUCinf (parametric) and Cmax
      (parametric) were 0.971 (0.886 approximately 1.063) and 0.982 (0.868
      approximately 1.107), respectively, satisfying the bioequivalence criteria of the
      European Committee for Proprietary Medicinal Products and the US Food and Drug
      Administration guidelines. The corresponding value of Tmax was 0.000 (-0.250
      approximately 0.250). CONCLUSION: These results indicate that the 2 medications
      of clarithromycin are bioequivalent and, thus, may be prescribed interchangeably.

PMID- 11515712
TI  - Party-drugs: sociocultural and individual background and risks.

PMID- 11515713
TI  - Potential economic impact of using a proprietary willow bark extract in
      outpatient treatment of low back pain: an open non-randomized study.
AB  - An open, non-randomised, study (postmarketing surveillance) was carried out on
      three groups of patients aged 18 to 80 presenting over an 18 month period with
      acute exacerbations of low back pain. The objective was to assess the possible
      economic impact of including a regular dose of proprietary willow bark extract
      (Assalix) in the treatment provided. A first group of 115 patients, presenting to
      3 general practitioners in the first 3 months, was prescribed a daily dose of
      extract containing 120 mg of salicin (group W120). They also had access, if
      necessary, to the range of conventional treatments allowed for in the general
      practitioners' budgets. A second group of 112 patients presenting to the same
      general practitioners over the next 15 months, was prescribed extract equivalent
      to 240 mg salicin per day (group W240). A third "control" or "comparator" group
      of 224 patients, presenting to 3 orthopedists (specialists in physical medicine)
      over the whole 18 month period, received only the conventional therapeutic
      options allowed in the orthopedists' budgets (Group C). In the group C patients,
      the exacerbations had been shorter but the pain had been more intense as judged
      by Arhus Index and Total Pain Index. After 4 weeks of treatment, about 40% of
      group W240 patients were free of pain whether or not they had to resort to
      supplementary treatments. In group W120 as a whole, about 19% of patients were
      pain-free at 4 weeks, but only 8% of those who did not resort to supplementary
      treatment. In group C, 18% of patients were painfree. These findings were
      reflected reasonably well in the changes in the Arhus Index and Total Pain Index,
      and the findings in group W240 were consistent with those in a previous
      randomised controlled trial. Multivariable modelling to examine for possible
      confounding effects tended to identify membership of group W240 as an independent
      explanator of better pain relief than membership of group C. Though the measures
      of effect tended to be similar in group W120 as a whole and group C, the
      avoidance of more expensive conventional treatments in group W120 meant that the
      average cost per patient of treatment was reduced by about 35-50% (health service
      and private costings respectively). The better pain relief in group W240 was
      accompanied by an even smaller reliance on supplementary conventional treatments
      than in group W120 but the extra savings on these were outweighed by the extra
      cost of the additional Assalix so that the average cost per patient was reduced
      by 14-40% of the costs in group C. The possibility is discussed that, if
      orthopedists had relied more on regular full dosing with NSAIDs, they might have
      increased the effectiveness and reduced the cost of their treatment, though with
      the possibility of more side effects. Substituting established NSAIDs with COX-2
      inhibitors might reduce the side effects, but at greater cost than with the
      Assalix.

PMID- 11515714
TI  - Double-blind, placebo-controlled, randomised cross-over clinical trial of
      NIPRISAN in patients with Sickle Cell Disorder.
AB  - The study was undertaken to determine the safety and efficacy of NIPRISAN, a
      phytomedicine, developed for the management of patients with Sickle Cell Disorder
      (SCD). The study design is a placebo-controlled double blind cross-over trial.
      Eighty-two (82) patients with SCD were recruited and randomised into two groups.
      An initial 4 month pre-trial study was undertaken to determine the similarity of
      the groups. The main study was conducted over a twelve-month period with
      crossover at six months. Safety of the drug was assessed clinically and
      biochemically. NIPRISAN significantly (P < 0.01) reduced the frequency of SCD
      crisis associated with severe pains. Acute toxicity to the liver assessed by the
      activities of liver enzymes, indicate that NIPRISAN is safe. Renal function
      assessed by the serum levels of creatinine and blood urea nitrogen remained
      normal. Both the clinical and laboratory results of the present phase IIB (pivot)
      clinical study suggest that NIPRISAN is a safe and efficacious phytomedicine for
      the management of patients with Sickle Cell Disorder.

PMID- 11515715
TI  - Clinical efficacy of crataegus extract WS 1442 in congestive heart failure NYHA
      class II.
AB  - In a randomised, placebo-controlled, double-blind clinical study the clinical
      efficacy and safety of Crataegus extract WS 1442, standardised to 18.75%
      oligomeric procyanidines, were investigated in 40 female and male outpatients
      suffering from congestive heart failure NYHA class II. Following a wash-out
      period of up to seven days, the patients were randomised to be treated for 12
      weeks with either WS 1442 (3 x 1 capsule) or placebo. The primary outcome
      variable was exercise tolerance determined with bicycle exercise testing; as a
      secondary outcome variable the difference of the double product was calculated.
      On average, the exercise tolerance increased by 66.3 W x min (10.8%) in the WS
      1442 group while in the placebo group a reduction of 105.3 W x min (16.9%) was
      measured. This difference between the groups was borderline statistically
      significant (p = 0.06). During the three month therapy the difference of the
      double product (heart rate x systolic blood pressure x 10(-2)) decreased by 14.4
      mmHg s(-1) (26.8%) in the WS 1442 group and by 1.3 mmHg s(-1) (2.7%) in the
      placebo group, respectively. Recording of laboratory parameters and adverse
      events showed that WS 1442 was safe and well tolerated. The data show that
      Crataegus extract WS 1442 is clinically effective in patients with congestive
      heart failure corresponding to NYHA class II.

PMID- 11515716
TI  - Persistent response to pneumococcal vaccine in individuals supplemented with a
      novel water soluble extract of Uncaria tomentosa, C-Med-100.
AB  - A human intervention study was carried out using male volunteers attending a
      General Practice Clinic in New York City involving comparison of individuals
      supplemented with 350 mg x 2 C-Med-100 daily dose for two months with untreated
      controls for their abilities to respond to a 23 valent pneumococcal vaccine. C
      Med-100 is a novel nutraceutical extract from the South American plant Uncaria
      tomentosa or Cat's Claw which is known to possess immune enhancing and
      antiinflammatory properties in animals. There were no toxic side effects observed
      as judged by medical examination, clinical chemistry and blood cell analysis.
      However, statistically significant immune enhancement for the individuals on C
      Med-100 supplement was observed by (i) an elevation in the lymphocyte/neutrophil
      ratios of peripheral blood and (ii) a reduced decay in the 12 serotype antibody
      titer responses to pneumococcal vaccination at 5 months.

PMID- 11515717
TI  - DNA repair enhancement of aqueous extracts of Uncaria tomentosa in a human
      volunteer study.
AB  - The Uncaria tomentosa water extracts (C-Med-100) have been shown to enhance DNA
      repair, mitogenic response and leukocyte recovery after chemotherapy-induced DNA
      damage in vivo. In this study, the effect of C-Med-100 supplement was evaluated
      in a human volunteer study. Twelve apparently healthy adults working in the same
      environment were randomly assigned into 3 groups with age and gender matched. One
      group was daily supplemented with a 250 mg tablet containing an aqueous extract
      of Uncaria tomentosa of C-Med-100, and another group with a 350 mg tablet, for 8
      consecutive weeks. DNA repair after induction of DNA damage by a standard dose of
      hydrogen peroxide was measured 3 times before supplement and 3 times after the
      supplement for the last 3 weeks of the 8 week-supplement period. There were no
      drug-related toxic responses to C-Med-100 supplement when judged in terms of
      clinical symptoms, serum clinical chemistry, whole blood analysis and leukocyte
      differential counts. There was a statistically significant decrease of DNA damage
      and a concomitant increase of DNA repair in the supplement groups (250 and 350
      mg/day) when compared with non-supplemented controls (p < 0.05). There was also
      an increased tendency of PHA induced lymphocyte proliferation in the treatment
      groups. Taken together, this trial has confirmed the earlier results obtained in
      the rat model when estimating DNA repair enhancement by C-Med-100.

PMID- 11515719
TI  - Differential long-term effects of tannic acid on adenyl cyclase activity and
      lipolysis in rat adipocytes.
AB  - Plants elaborate a variety of secondary metabolites such as hydrolysable tannins
      which are relatively abundant in fruits, vegetables and beverages in the human
      diet. We have studied the in vivo long-term effect consumption of tannic acid
      supplemented drinking water (0.05%, w/v) on the rat adipocyte adenyl cyclase
      system and on lipolysis. We found that 14-day tannic acid supplementation did not
      significantly affect either body growth or food consumption, while fat pads
      weight was higher than that of the control, although the difference was not
      significant. On the other hand, tannic acid supplementation decreased both basal
      and isoproterenol-stimulated lipolysis significantly whereas cyclic AMP
      production as well as adenyl cyclase activity increased significantly. These
      results are at a first glance contradictory as cyclic AMP accumulation and
      lipolysis are positively correlated in rat adipocytes. They suggest at least that
      the tannic acid diet led to an inhibition of cyclic AMP-dependent protein kinase
      activity followed by a decrease in lipolysis in rat adipocytes, and to an
      increased activity of the type VI adenyl cyclase subunit of rat fat cells. This
      subunit is known to be negatively regulated under phosphorylation by cyclic AMP
      dependent protein kinase. More in-depth studies are required to examine whether
      tannic acid could at least modify the expression of the catalytic subunit of
      adenyl cyclase, G-proteins and cyclic AMP-dependent protein kinase and/or alter
      their activities.

PMID- 11515718
TI  - Adaptogenic activity of a glyco-peptido-lipid fraction from the alcoholic extract
      of Trichopus zeylanicus Gaertn.
AB  - A glyco-peptido lipid fraction ("AF") from the alcoholic extract of Trichopus
      zeylanicus Gaertn. was evaluated for putative antistress activity in a battery of
      tests. "AF" exhibited significant antistress activity in dose dependent manner in
      all the parameters studied, against the different stresses use to induce non
      specific stress. Ashwagandha, the commercial extract of Withania somnifera roots
      was used as control: A preliminary acute toxicity study in mice showed a good
      margin of safety, as the ALD50 value was more than 3000 mg/kg body wt. p.o. with
      no signs of abnormalities.

PMID- 11515720
TI  - Evaluation of anti-tussive activity of Bergenia ciliata Sternb. rhizome extract
      in mice.
AB  - The methanol extract of the rhizome of Bergenia ciliata Sternb. (Saxifragaceae)
      has been evaluated for its potential in a cough model induced by sulphur dioxide
      gas in mice. The extract exhibited significant anti-tussive activity in a dose
      dependent manner, as compared with control. The antitussive activity of the
      extract was comparable to that of codeine phosphate (10 mg/kg body wt.), a
      standard anti-tussive agent. The extract at doses of 100, 200 and 300 mg/kg body
      wt. (p.o.) showed significant inhibition of cough reflex by 28.7, 33.9 and 44.2%,
      respectively, within 90 min of the experiment.

PMID- 11515721
TI  - Antimicrobial evaluation of coumarins and flavonoids from the stems of Daphne
      gnidium L.
AB  - The antimicrobial activity of stems methanol extract from Daphne gnidium L.
      collected from Sardinia (Italy) was evaluated against 6 strains of standard and
      clinical isolated gram (+/-) bacteria. The antimicrobial effect on two strains of
      fungi was also tested. The extract in toto exhibited antibacterial activity
      against Bacillus lentus and Escherichia coli, but was inactive against fungi.
      Four coumarins (daphnetin, daphnin, acetylumbelliferone, daphnoretin) and seven
      flavonoids (luteolin, orientin, isoorientin, apigenin-7-O-glucoside, genkwanin, 5
      O-beta-D-primeverosyl genkwanine, 2,5,7,4'-tetrahydroxyisoflavanol) present in
      the plant extract were also investigated against the same strains of bacteria and
      fungi assayed for the crude extract. The most active compounds were daphnetin,
      genkwanin, and 2,5,7,4'-tetrahydroxyisoflavanol.

PMID- 11515722
TI  - Role of flavonoids in controlling the phototoxicity of Hypericum perforatum
      extracts.
AB  - Hypericum perforatum extracts are used mainly as oral antidepressants. Depending
      on source the extracts contain various amounts of phenylpropanes, flavonol
      derivates, biflavones, proathocyanidines, xanthones, phloroglucinoles, some amino
      acids, naphtodianthrones (hypericines) and essential oil constituents. The
      therapeutic use of Hypericum perforatum extracts however is limited by their
      phototoxic potential. It was the aim of the present study to investigate the
      phototoxic potential of 3 Hypericum perforatum extracts from different sources as
      well as some of its main constituents. In order to systematically study the
      phototoxic potential we established a modified neutral red assay utilizing an
      immortalized human keratinocyte cell line (HaCaT cells) as substrate and UVA
      irradiation. This modified neutral red assay was found to be a simple and
      reliable method for detecting phototoxic effects of reference agents and plant
      extracts. The validity of this method was demonstrated with known phototoxic
      compounds like chloropromazine and psoralenes like 5-MOP. Hypericum perforatum
      extracts demonstrated cytotoxicity and photocytotoxicity in a dose and UVA-dose
      dependent manner. Hypericine itself also evoked severe phototoxic effects and was
      thus identified as the main phototoxic constituent. Among the tested flavonoids
      quercitrin was found to be cytotoxic, while rutin unexpectedly demonstrated
      phototoxicity whereas quercitrin was effective to control the phototoxic activity
      of Hypericum perforatum extracts.

PMID- 11515723
TI  - Plants with central analgesic activity.
AB  - The present communication constitutes a global review on plant analgesic activity
      with special emphasis on those found in different parts of the world, including
      Brazil, which act on the central nervous system. One hundred and sixty six plants
      belonging to 79 families are reported.

PMID- 11515725
TI  - Osteoporosis in children and adolescents: diagnosis, risk factors, and
      prevention.
AB  - Bone mass acquired during childhood and adolescence is a key determinant of adult
      bone health. Peak bone mass, which is achieved in late adolescence, is a main
      determinant of osteoporosis in adulthood. Therefore, any factor adversely
      impacting on bone acquisition during childhood or adolescence can potentially
      have long-standing detrimental effects on bone health predisposing to
      osteoporosis and fracture risk. Thus, osteoporosis can well have its origin in
      childhood and adolescence. Pediatricians should be playing an active role in
      osteoporosis diagnosis and prevention. It is increasingly recognized that
      osteoporosis may occur in some disorders of children and adolescents. In this
      paper we review the diagnostic criteria of osteopenia/osteoporosis by
      densitometric assessment of bone mineral density, the contributing factors, and
      the mechanisms whereby several disorders may affect the acquisition of bone mass
      in children and adolescents. Finally, some recommendations to optimize peak bone
      mass in order to prevent osteopenia/osteoporosis are suggested.

PMID- 11515724
TI  - Osteoporosis in childhood: bone density of children in health and disease.
AB  - Bone mineral density in later life largely depends on the peak bone mass achieved
      in adolescence or young adulthood. A reduced bone density is associated with
      increased fracture risk in adults as well as in children. Pediatricians should
      therefore play an important role in the early recognition and treatment of
      childhood osteoporosis. Juvenile idiopathic osteoporosis and osteogenesis
      imperfecta are examples of primary osteoporosis in childhood. However,
      osteoporosis is more frequently a complication of a chronic disease or its
      treatment. This paper provides an overview of bone and bone metabolism in healthy
      children and the use of diagnostic tools, such as biochemical markers of bone
      turnover and several bone densitometry techniques. Furthermore, a number of
      diseases associated with osteoporosis in childhood and possible treatment
      strategies are discussed.

PMID- 11515726
TI  - Morbidity and mortality associated with vasopressin replacement therapy in
      children.
AB  - OBJECTIVE: To assess the incidence and associated risk factors of adverse
      reactions of DDAVP treatment of children with diabetes insipidus, comparing
      different routes of administration. DESIGN: We retrospectively studied 103
      children (44 females, 59 males) with cranial diabetes insipidus (mean age 6.9
      years at diagnosis) treated with intramuscular (59), intranasal (84) and/or oral
      (64) DDAVP, over a mean follow-up period of 5.2 years. RESULTS: Eight patients
      died. For at least two children death was related to water intoxication. Major
      complications (symptomatic water overload with or without seizures) or
      asymptomatic hyponatraemia were observed in 33 patients. The incidence of total
      complications was significantly higher in cortisol deficient patients than in
      those with normal cortisol reserve (36% vs 6%). In patients on concomitant
      carbamazapine treatment major complications were more frequent in comparison to
      the remaining patients (33% vs 10%). Although not achieving significance, there
      were fewer complications using the oral route. CONCLUSIONS: Caution is needed in
      managing patients with DI, especially if risk factors such as cortisol deficiency
      or concomitant carbamazepine treatment are present. The oral route of
      administration seems to be preferred for both convenience and safety. Major
      changes in dose and formulation should be undertaken in hospital.

PMID- 11515727
TI  - Endocrine sequelae of childhood craniopharyngioma.
AB  - The endocrine sequelae of 62 children with craniopharyngioma were studied
      retrospectively. These patients were followed for a median duration of 3 years
      (range 1 to 10 years). Eighteen patients had a long-term follow-up for more than
      5 years (range 5 to 10 years). Complete surgical resection was achieved in 30
      patients and 32 patients had residual tumor. Twenty-five patients had recurrence
      or progression of the residual tumor and were treated with radiotherapy.
      Presenting complaints suggestive of endocrinopathy were infrequent. The most
      common presenting symptoms were headache, nausea and vomiting, followed by growth
      failure. Pre-operatively, growth hormone deficiency was the most commonly
      encountered pituitary hormonal deficiency; however postoperatively, most children
      had diabetes insipidus. Multiple pituitary hormonal deficiencies were more
      frequently observed in children treated with extensive radical surgery than in
      those treated with conservative surgery and radiotherapy. The endocrine morbidity
      associated with craniopharyngioma and its different management modalities remains
      high; however, it is manageable with appropriate hormonal replacement therapy.

PMID- 11515728
TI  - Relationship between renal volume and increased albumin excretion rates in
      children and adolescents with type 1 diabetes mellitus.
AB  - OBJECTIVE: To compare renal volume in a group of prepubertal and pubertal
      children with type 1 diabetes mellitus (DM) and either borderline
      microalbuminuria (BM) or intermittent microalbuminuria (IM) with a matched group
      of normoalbuminuric (NA) controls with DM. RESEARCH DESIGN AND METHODS: Twenty
      one patients with BM or IM were matched for age, gender and duration of DM with
      an NA control group. Total renal volume (RV), measured by ultrasound, was
      corrected for body surface area. Long-term diabetes control was assessed by
      glycosylated haemoglobin levels. RESULTS: There were no significant differences
      in age, duration of DM or glycosylated haemoglobin levels between the groups.
      Those with BM or IM had significantly increased total renal volume (303 +/- 8.4
      ml/1.73 m2) compared to those with NA (276.3 +/- 10 ml/1.73 m2) (T40=2.04,
      P=0.05). Multivariate modelling suggested that this association was independent
      of potential confounding covariates. While not formally significant
      (chi2(1)=2.53, P=0.12), the frequency of nephromegaly (RV >300 ml/1.73 m2) was
      doubled in children with BM or IM (47.6%) compared to controls (23.8%).
      Nephromegaly was not found in prepubertal patients. CONCLUSIONS: This study
      suggests that nephromegaly is more common in patients with borderline increases
      in urinary albumin excretion rates (AER) than those with normoalbuminuria.
      Prospective follow-up of those with increased renal volume is needed to determine
      whether nephromegaly is an early marker of incipient nephropathy.

PMID- 11515729
TI  - Height velocity in Argentinean girls with Turner's syndrome.
AB  - Height velocities from birth to maturity derived from 1,049 height increments
      measured over intervals 0.85-1.15 years were studied from a sample of 187
      patients with Turner's syndrome (TS) diagnosed on the basis of karyotype. Length
      of follow up in each girl varied from 1.0 to 11.0 years. Cross-sectional analysis
      showed a relatively stable growth velocity during pubertal ages. However,
      longitudinal analysis of individual growth curves showed the existence of a small
      growth spurt in 37 out of 47 girls with available data during pubertal years.
      Mean peak height velocity (PHV) of this spurt was 5.7 cm/year, SD 1.34; mean age
      at PHV was 12.66 years, SD 1.70. Selected percentiles were calculated using the
      least mean squares (LMS) method. Results show that a small growth spurt in girls
      with TS may be more frequent than previously thought.

PMID- 11515730
TI  - Transient neonatal diabetes mellitus in a child with paternal uniparental disomy
      of chromosome 6.
AB  - We report a male infant with transient neonatal diabetes mellitus (TNDM; MIM
      601410), macroglossia, hypertelorism, umbilical hernia, inguinoscrotal hernia and
      onychomycosis. Diabetes mellitus was diagnosed 10 days after birth and resolved
      after 6.5 months of treatment. Genetic investigation indicated the presence of
      paternal uniparental disomy of chromosome 6 (UPD 6). The finding of paternal UPD
      6 allows prediction of a transient, rather than permanent NDM, and no increased
      recurrence risk of TNDM in subsequent pregnancies. Therefore, finding of NDM
      should be a strong indicator for genetic testing.

PMID- 11515731
TI  - Central precocious puberty in a girl with triple X syndrome and neonatal diabetes
      mellitus associated with paternal isodisomy of chromosome 6.
AB  - We describe a girl with triple X syndrome and paternal isodisomy of chromosome 6
      (UPD6), who developed neonatal diabetes mellitus (NDM) and precocious puberty. At
      birth she presented growth retardation and congenital anomalies (ventricular
      septal defect, macroglossia, umbilical hernia). Diabetes mellitus (DM) was
      diagnosed at 31 days of life and treated with insulin for 13 months. DM recurred
      at 4 years of age and since that time it required insulin, in spite of preserved
      beta-cell function. Tall stature was present from early childhood. At 7 years of
      age the girl presented central precocious puberty, height velocity further
      increased, but her near-final height was normal. This patient is unique in that
      precocious puberty has never been described in triple X females. Moreover it is a
      further example of paternal UPD6 causing NDM with a predisposition to type 2 DM
      in later life.

PMID- 11515732
TI  - Severe hypothyroidism due to autoimmune atrophic thyroiditis--predicted target
      height and a plausible mechanism for sexual precocity.
AB  - Autoimmune thyroiditis, the most frequent cause of acquired hypothyroidism in
      childhood and adolescents, is characterized by raised levels of the specific
      antibodies to thyroperoxidase (TPOAb) and thyroglobulin (TgAb). We report a girl
      aged 10 years and 9 months who presented with arrested growth and breast
      development (thelarche). She also exhibited myxedema of the face and legs,
      prominent striae on the thighs, dry, cold skin, and hypertrichosis on her back.
      There was no goiter, no history of thyroid pain and no family history of thyroid
      disease. She complained occasionally of a transient headache. The patient's
      height was below the 3rd percentile, while her body weight was at the 50th
      percentile and bone age was normal. Laboratory tests proved severe hypothyroidism
      (fT4 0 ng/dl, fT3 0.99 pg/ml, TSH >100 microIU/ml plus an increased titer of
      TPOAb). Thyroid ultrasound supported the diagnosis of thyroiditis. Pituitary PRL
      and FSH levels and peripheral estradiol were all elevated. L-Thyroxine therapy,
      instituted following diagnosis, improved the growth velocity to 11 cm/year and
      the FSH and E2 levels were normalized to prepubertal values. Complete regression
      of the breast development was observed within 4 months. However, 4 months later a
      true (central), isosexual LHRH-dependent puberty started. The pubertal features
      at the time of the original diagnosis might be explained by: 1. the direct action
      of elevated TRH on gonadotropes to stimulate gonadotropin secretion and on
      lactotrophes to stimulate PRL secretion, and 2. TSH action on LH and mostly FSH
      receptors (homologous to TSH receptors) in the ovary, stimulating the secretion
      of estradiol.

PMID- 11515733
TI  - Autoimmune polyglandular endocrinopathy and anterior hypophysitis in a 14 year
      old girl presenting with delayed puberty.
AB  - We report a 14 year-old peripubertal girl who presented at our clinic with the
      primary complaint of delayed puberty. She was asymptomatic except for vague
      complaints of fatigue. Physical examination was significant for mucosal
      hyperpigmentation and lack of secondary sexual characteristics. Laboratory
      evaluation revealed a morning cortisol concentration of <0.1 microg/dl (normal
      range [n.r.]: 4.3-22.4 microg/dl) and a simultaneous ACTH concentration of 2
      pg/ml (n.r. 25-62 pg/ml); FSH 66.8 IU/l (n.r. for age: 1-12.8 IU/l); LH 41.1 IU/l
      (n.r. for age: 1-12 IU/l); E2 38 pg/ml (n.r. for age: 7-60 pg/ml). She had a flat
      cortisol response to an ACTH stimulation test. MRI of the pituitary gland failed
      to reveal a lesion. Plasma renin activity, thyroid function tests, parathyroid
      hormone, prolactin, IGF-I, IGFBP-3 concentrations and serum electrolytes were
      normal. However, her urinary sodium concentration was high. She was diagnosed
      with autoimmune polyglandular endocrinopathy including ovarian failure, adrenal
      failure and autoimmune anterior hypophysitis presenting as isolated ACTH
      deficiency. We emphasize that autoimmune etiology should be considered in the
      differential diagnosis of delayed puberty and ovarian failure and that the
      presence of other endocrinopathies should be searched for even in asymptomatic
      patients.

PMID- 11515734
TI  - Severe hypercalcemia of an infant due to vitamin D toxicity associated with
      hypercholesterolemia.
AB  - We report an 11 month-old infant with severe hypercalcemia associated with
      hyperlipidemia following bolus vitamin D administration. At the time of
      admission, serum concentration of calcium was 5.5 mmol/l (22 mg/dl); total
      cholesterol, high density lipoprotein cholesterol (HDL-C), very low density
      lipoprotein (VLDL), low density lipoprotein cholesterol (LDL-C), and triglyceride
      levels were respectively: 6.37 mmol/l (246 mg/dl), 0.77 mmol/l (30 mg/dl), 1.37
      mmol/l (54 mg/dl), 4.1 mmol/l (162 mg/dl), 3 mmol/l (271 mg/dl). Physical
      examination revealed dehydration and irritability that was inappropriately mild
      according to the serum calcium level. On the 16th day of therapy that consisted
      of intravenous fluids with furosemide (sodium diuresis), steroid, calcitonin,
      magnesium sulfate, and phosphorus, serum calcium level declined below 3 mmol/l
      (12 mg/dl). The hyperlipidemia resolved gradually with a concomitant decline in
      serum calcium. This report is interesting in that hypercalcemia was associated
      with transient hyperlipidemia that disappeared with normocalcemia, which might
      suggest protection against hypercalcemic symptoms.

PMID- 11515735
TI  - First World Congress on the Fetal Origins of Adult Disease.

PMID- 11515736
TI  - Social relationships, social support, and patterns of cognitive aging in healthy,
      high-functioning older adults: MacArthur studies of successful aging.
AB  - This study examines the relationship of social ties and support to patterns of
      cognitive aging in the MacArthur Studies of Successful Aging (see L. F. Berkman
      et al., 1993), a cohort study of 1,189 initially high-functioning older adults.
      Baseline and longitudinal data provide information on initial levels as well as
      changes in cognitive performance over a 7.5-year period. Linear regression
      analyses revealed that participants receiving more emotional support had better
      baseline performance, as did those who were unmarried and those reporting greater
      conflict with network members. Greater baseline emotional support was also a
      significant predictor of better cognitive function at the 7.5-year follow-up,
      controlling for baseline cognitive function and known sociodemographic,
      behavioral, psychological, and health status predictors of cognitive aging. The
      findings suggest the potential value of further research on the role of the
      social environment in protecting against cognitive declines at older ages.

PMID- 11515738
TI  - Exercise duration and mood state: how much is enough to feel better?
AB  - The effects of exercise duration on mood state were examined. In a repeated
      measures design, the Profile of Mood States inventory (D. M. McNair, M. Lorr, &
      L. F. Droppleman, 1971) was administered before and after 1 quiet resting trial
      and 3 exercise trials of 10, 20, and 30 min on a bicycle ergometer. Heart rate
      levels were controlled at 60% of the participant's estimated VO2max level. An
      overall analysis of variance found improved levels of vigor with reduced levels
      of confusion, fatigue, and total negative mood. Planned analyses revealed that
      the improvements in vigor, fatigue, and total mood occurred after 10 min of
      exercise, with progressive improvements in confusion over 20 min and with no
      additional improvement over longer periods. These results complement current
      recommendations, which suggest that to experience positive fitness and health
      benefits, healthy adults should participate in a total of 30 min of moderate
      physical exercise daily, accumulated in short bouts throughout the day.

PMID- 11515737
TI  - The effects of message framing and ethnic targeting on mammography use among low
      income women.
AB  - The authors examined the effects that differently framed and targeted health
      messages have on persuading low-income women to obtain screening mammograms. The
      authors recruited 752 women over 40 years of age from community health clinics
      and public housing developments and assigned the women randomly to view videos
      that were either gain or loss framed and either targeted specifically to their
      ethnic groups or multicultural. Loss-framed, multicultural messages were most
      persuasive. The advantage of loss-framed, multicultural messages was especially
      apparent for Anglo women and Latinas but not for African American women. These
      effects were stronger after 6 months than after 12 months.

PMID- 11515739
TI  - Women's beliefs about the prevalence of premenstrual syndrome and biases in
      recall of premenstrual changes.
AB  - The present study investigated the relationship between women's beliefs about the
      prevalence of premenstrual syndrome (PMS) and biases in recall of premenstrual
      changes. Forty-nine women completed the Moos Menstrual Distress Questionnaire (R.
      H. Moos, 1968) both retrospectively and prospectively. Afterward, they were asked
      about their beliefs concerning the prevalence of PMS. The women reported higher
      premenstrual changes when they completed the retrospective questionnaire. Seventy
      five percent of the women believed that the majority of women have premenstrual
      changes. From this percentage, those who answered that the majority also
      experience PMS were more biased in their premenstrual changes in the
      retrospective assessment. Many women have a misperception about the meaning of
      PMS; consequently, they amplify their premenstrual changes in recall, reflecting
      women's cultural stereotypes rather than their actual experiences.

PMID- 11515740
TI  - Conceptualizing the multidimensional nature of self-efficacy: assessment of
      situational context and level of behavioral challenge to maintain safer sex.
      National Institute of Mental Health Multisite HIV Prevention Trial Group.
AB  - A. Bandura (1991) argued that self-efficacy measurement should be specific both
      to the situation in which the behavior occurs and level of challenge in that
      situation. Measures consistent with the 2 dimensions were developed with graded
      challenge levels and differing gender-appropriate situations. Participants were
      1,496 controls in the National Institute of Mental Health Multisite HIV
      Prevention Trial recruited from STD clinics and health service centers (925 women
      and 571 men). The authors tested 4 separate-sex confirmatory factor analysis
      models as follows: (a) Condom negotiation efficacy as a unitary construct across
      situations and gradation of difficulty; (b) situation as preeminent, which
      transfers across skills whatever the gradation of difficulty; (c) skill as
      predominant, irrespective of situation; and (d) a multidimensional design that
      simultaneously accounts for both situation and graded difficulty. Consistent with
      Bandura's theory, the multidimensional model provided the best fit for both
      samples.

PMID- 11515741
TI  - Are negative affective states associated with HIV sexual risk behaviors? A meta
      analytic review.
AB  - This meta-analytic review examined whether negative affective states (depressive
      symptomatology, anxiety, anger) are associated with sexual behaviors that place
      people at risk for contracting or transmitting HIV. The results from 34 study
      samples were included in the analysis. Contrary to popular belief, the findings
      as a whole provide little evidence that negative affect is associated with
      increased sexual risk behavior. The average weighted correlation for the overall
      association was .05. The effect size was nonsignificantly higher for anger (r =
      .10) than for depressive symptoms (r = .04) or anxiety (r = .03). The variability
      of effect sizes was not accounted for by type of sexual risk measure, subject
      population, or methodological aspects of the studies. Conceptual and
      methodological limitations of the literature are identified and directions for
      future research are discussed.

PMID- 11515742
TI  - Negative affect and sexual risk behavior: comment on Crepaz and Marks (2001).
AB  - In this commentary, the authors highlight the findings of the meta-analysis by N.
      Crepaz and G. Marks (2001). The role of affect in sexual risk behavior, although
      intuitively obvious, is not well understood and has been largely ignored by HIV
      prevention researchers in favor of social-cognitive models of behavior. Crepaz
      and Marks synthesized the results from studies that have examined the relation of
      negative affect (e.g., depression, anxiety, anger) to sexual risk behavior and
      concluded that in the literature to date, these variables appear unrelated. The
      authors suggest that the Crepaz and Marks findings are not surprising given the
      methods used in the reviewed studies and suggest methodological approaches that
      will allow more sensitive analyses of the association between affect and sexual
      risk behavior.

PMID- 11515743
TI  - Physician-assisted dying: review of issues and roles for health psychologists.
AB  - The authors review the recent empirical and theoretical literature on physician
      assisted dying (PAD) since implementation of the Oregon Death With Dignity Act
      (ODDA) in 1997. The authors provide a brief overview of end-of-life practices;
      consider ethical and practical issues regarding PAD; outline governments' acts
      and health care organizations' current codified principles regarding PAD,
      including the American Psychological Association's goal to increase the
      visibility of psychology in end-of-life issues; examine recent data pertinent to
      ODDA implementation and psychologists' attitudes regarding PAD; and outline
      potential roles for health psychologists responding to requests for PAD and
      implementing PAD (where it is legal). Health psychologists can assume at least 4
      roles regarding PAD: (a) policy advocates, (b) educators, (c) practitioners, and
      (d) researchers.

PMID- 11515744
TI  - Cultured human foetal cerebral cortex, transfected with tyrosine hydroxylase
      cDNA, as a source of neural transplant material.
AB  - Obtaining an adequate supply of foetal dopaminergic tissue to treat Parkinson's
      disease by neural transplantation can be difficult. In this study primary
      cultures of human foetal cerebral cortex cells were transfected, using cationic
      lipids, with a eukaryotic expression vector (pCIneo-THI) containing the cDNA for
      human tyrosine hydroxylase isoform I (TH). Cortical cells from human (10-14 week)
      foetuses were cultured for 11 days in vitro and transfected twice with pCIneo-THI
      during this time. The double transfection process resulted in 3-4% of the cells
      becoming TH positive. When grafted into the striatum of 6-OHDA lesioned rats the
      transfected foetal cerebral cortex cells reduced amphetamine-induced circling
      behaviour by 75%, while grafts of untransfected cells had no significant effect
      on turning. TH transfected foetal cerebral cortex cells may therefore be a useful
      alternative supply of tissue for use in neural transplants to treat Parkinson's
      disease.

PMID- 11515745
TI  - Responsiveness of plasma catecholamines to intracerebroventricular injection of
      glucagon in Muscovy ducklings.
AB  - Recent investigations have demonstrated a modulatory action of glucagon on
      shivering via the central nervous system in ducklings. The aim of this study was
      to investigate the effects of intracerebroventricular injection (i.c.v.) of
      glucagon on metabolic rates (MR) and plasma catecholamines in control ducklings
      (TN) and in ducklings exhibiting nonshivering thermogenesis after chronic
      glucagon treatment: (GT). At thermoneutrality (25 degrees C, Ta), i.c.v.
      injection of glucagon had no thermogenic effects in TN and GT ducklings. At cold
      (+4 degrees C, Ta), i.c.v. glucagon injection elicited a concomitant decrease of
      plasma norepinephrine (NE) and MR in TN ducklings, whereas in GT ducklings, the
      plasma catecholamines and the MR remained unchanged. These results indicate that
      glucagon treatment rendered the catecholaminergic system of GT ducklings
      insensitive to cold or i.c.v. glucagon injection.

PMID- 11515746
TI  - Dopamine transporter immunoreactivity in peripheral blood lymphocytes in
      Parkinson's disease.
AB  - There is increasing interest in the identification of biological markers for the
      early diagnosis of Parkinson's disease (PD). Previous studies indicate changes of
      dopamine content, tyrosine hydroxylase immunoreactivity and dopamine receptors in
      peripheral blood lymphocytes (PBL) in PD. Here we demonstrate a reduction of
      dopamine transporter immunoreactivity in PBL in the early clinical stages of the
      disease. These findings contribute to our understanding of the peripheral
      dopamine system in PD.

PMID- 11515747
TI  - Chronic elevation of amyloid precursor protein in the neocortex or hippocampus of
      marmosets with selective cholinergic lesions.
AB  - In vitro studies have consistently demonstrated a link between cholinergic
      neurotransmission and amyloid precursor protein metabolism, although few studies
      have examined such a relationship in vivo and none have been conducted in primate
      species. The purpose of this study was to test the hypothesis that a reduction in
      cholinergic activity in neocortical and hippocampal areas consequent upon
      destruction of ascending cholinergic projections may lead to long-term changes in
      levels of amyloid precursor protein in these target areas in a primate species.
      The status of three synaptic proteins associated with neurotransmitter release,
      synaptophysin, syntaxin and SNAP-25, was also been examined. Selective
      immunolesions of the basal forebrain cholinergic projections led to increases in
      amyloid precursor protein-like immunoreactivity in hippocampus and cortex,
      measured 8 months postlesion. Furthermore, reductions in cortical and hippocampal
      SNAP-25, but not syntaxin or synaptophysin, immunoreactivity were observed. These
      results imply that the reduced cholinergic activity characteristic of Alzheimer's
      disease may contribute to the continuing emergence of neuropathology in addition
      to the well-known association with cognitive dysfunction.

PMID- 11515748
TI  - Different pattern of reduction of striatal dopamine reuptake sites in Alzheimer's
      disease and ageing.
AB  - Striatal dopamine reuptake sites were studied in brain samples from 14
      Alzheimer's disease (AD) patients. A cocaine analogue, [3H]CFT (WIN 35,428, 2beta
      carbomethoxy-3beta-(4-fluorophenyl)-tropane) was used as a radioligand to
      determine the number of [3H]CFT binding sites (Bmax) and their dissociation
      constant (Kd). In patients with AD the reduction in [3H]CFT binding in the
      putamen was about 50% compared to age-matched controls. In the caudate nucleus
      the reduction was about 33%. Thus, the putamen was more severely affected. No
      change was observed in Kd values between AD patients and controls. Brain samples
      from 37 healthy controls (aged from 8 to 91 years) were used to study the changes
      in striatal [3H]CFT binding with increasing age. The Bmax of [3H]CFT uptake was
      reduced both in the putamen and in the caudate nucleus. The average decline per
      decade was greater in the caudate nucleus (7.3%) than in the putamen (5.5%). In
      conclusion, the pattern of changes in AD is different from that seen during
      normal ageing, which seems to affect more severely the caudate nucleus than the
      putamen.

PMID- 11515749
TI  - Association studies of the cholecystokinin B receptor and A2a adenosine receptor
      genes in panic disorder.
AB  - Several lines of evidence implicate the cholecystokinin B receptor (CCKBR) and
      the A2a adenosine receptor (A2aAR) in the etiology of panic disorder. To
      determine the roles each of these receptors may play in panic disorder, we have
      performed a mutation screen on the CCKBR gene using single strand conformation
      polymorphism (SSCP) analysis and sequencing. We identified two novel but rare
      substitutions in the same allele, [3263G>C; 3264A>G], located in the 3'
      untranslated region of the CCKBR gene. We then analyzed 91 unrelated patients and
      100 matched controls for the four confirmed polymorphic sites in the CCKBR gene
      and the 1083C>T polymorphism in the A2aAR gene. No evidence of association
      between the described variants and panic disorder was found. Our data therefore
      suggests that the CCKBR and A2aAR genes do not play major roles in the
      development of this disease.

PMID- 11515750
TI  - Association analysis of the pituitary adenyl cyclase activating peptide gene
      (PACAP) on chromosome 18p11 with schizophrenia and bipolar disorders.
AB  - In neurons, pituitary adenyl cyclase activating peptide (PACAP) stimulates
      signaling cascades, involving cAMP and calcium. PACAP appears to play a role in
      up-regulation of tyrosine hydroxylase and dopamine beta-hydroxylase via protein
      kinase C and/or protein kinase A. Furthermore, the PACAP gene (ADCYAP1) is
      located in chromosome 18p11, where linkage of bipolar disorders and schizophrenia
      has been reported. In this study, we scanned the coding region of the PACAP gene
      for mutations in 24 Japanese patients with schizophrenia and 24 Japanese patients
      with bipolar disorders. No variant in the coding region was found. One
      polymorphism, INV3-37A/T, in the third intron was detected. Case-control
      comparisons revealed no significant association between this polymorphism and
      schizophrenia or bipolar disorders. This study did not provide evidence for the
      contribution of the PACAP gene to the etiology of schizophrenia or bipolar
      disorders in the Japanese population.

PMID- 11515751
TI  - A hypothalamic digoxin mediated model for conscious and subliminal perception.
AB  - The isoprenoid pathway and its metabolites--digoxin, dolichol and ubiquinone were
      assessed in schizophrenia. There was an upregulation of the isoprenoid pathway as
      evidenced by elevated HMG CoA reductase activity. Digoxin, an endogenous Na+-K+
      ATPase inhibitor secreted by the hypothalamus was found to be elevated and RBC
      membrane Na+-K+ ATPase activity was found to be reduced in schizophrenia.
      Membrane Na+-K+ ATPase inhibition can result in increased intracellular Ca2+ and
      reduced magnesium levels. Hypothalamic digoxin can modulate conscious and
      subliminal perception and its dysfunction may lead on to schizophrenia. Digoxin
      can also preferentially upregulate tryptophan transport over tyrosine resulting
      in increased levels of depolarising tryptophan catabolites--serotonin and
      quinolinic acid (NMDA agonist), and decreased levels of hyperpolarising tyrosine
      catabolites--dopamine and noradrenaline contributing to membrane Na+-K+ ATPase
      inhibition. NMDA excitotoxicity could result from hypomagnesemia induced by
      membrane Na+-K+ ATPase inhibition and quinolinic acid, an NMDA agonist acting on
      the NMDA receptor. Hypomagnesemia and increased dolichol level can affect
      glycoconjugate metabolism and membranogenesis leading on to disordered synaptic
      connectivity in the limbic allocortex and defective presentation of viral
      antigens and neuronal antigens contributing to autoimmunity and viral persistance
      important in the pathogenesis. Membrane Na+-K+ ATPase inhibition can produce
      immune activation, a component of autoimmunity. Mitochondrial dysfunction
      consequent to altered calcium/magnesium ratios and reduced ubiquinone levels can
      result in increased free radical generation and reduced free radical scavenging &
      defective apoptosis leading on to abnormal synaptogenesis. Schizophrenia can thus
      be considered as a syndrome of hypothalamic digoxin hypersecretion consequent to
      an upregulated isoprenoid pathway.

PMID- 11515752
TI  - CSF studies in violent offenders. I. 5-HIAA as a negative and HVA as a positive
      predictor of psychopathy.
AB  - Low serotonin activity in man has been related to impulsive, self-destructive
      violence but not to instrumental aggression aimed at dominance. A relationship
      has also been suggested between aggression and high catecholaminergic activity.
      Several studies have reported signs of aberrant dopaminergic function in
      attention deficit hyperactivity disorder, autism, and schizophrenia. In 22
      violent offenders undergoing pretrial forensic psychiatric investigation,
      interpersonal and behavioral features of psychopathy, measured by the Psychopathy
      Checklist Revised (PCL-R), were significantly predicted by low cerebrospinal
      fluid (CSF) concentrations of 5-HIAA and high CSF concentrations of HVA in
      multivariate regression models. CSF concentrations of MHPG did not contribute to
      the model. This seems to link the outward-directed aggression of psychopathy to
      serotonergic hypofunctioning and high dopamine turnover, which might account for
      disinhibition of destructive impulses.

PMID- 11515753
TI  - CSF studies in violent offenders. II. Blood-brain barrier dysfunction without
      concurrent inflammation or structure degeneration.
AB  - Cerebral dysfunction without corresponding structural pathology has been reported
      in brain imaging studies of violent offenders. Biochemical markers in the CSF
      reflect various types of CNS pathology, such as blood-brain barrier dysfunction
      (CSF/S albumin ratio), infectious or inflammatory processes (IgG and IgM
      indices), neuronal or axonal degeneration (CSF-tau protein) and synaptic de- or
      regeneration (CSF-growth associated protein-43 (GAP-43)). We compared these CSF
      markers in 19 non-psychotic perpetrators of severe violent crimes undergoing
      pretrial forensic psychiatric investigation and 19 age- and sex-matched controls.
      Index subjects had significantly higher albumin ratios (p = 0.002), indicating
      abnormal vascular permeability as part of the complex CNS dysfunction previously
      reported in violent offenders. Axis I disorders, including substance abuse or
      current medication, did not explain this finding. Since Ig-indices, CSF-tau
      protein or CSF-GAP-43 were not increased, there was no support for inflammation
      or neuronal/synaptic degeneration as etiological factors to CNS dysfunction in
      this category of subjects.

PMID- 11515754
TI  - Alcohol-associated stimuli activate the ventral striatum in abstinent alcoholics.
AB  - Alcohol-associated cues may act as conditioned stimuli that activate the brain
      reward system and motivate alcohol intake in alcoholics. Alcohol-associated
      visual stimuli were presented during functional magnetic resonance imaging. An
      activation of the ventral putamen was observed in alcoholics but not in control
      subjects. Patients with a strong activation of the ventral putamen relapsed
      during the next three months. This observation supports the hypothesis that
      alcohol use affects areas involved in brain reward circuits and that their
      stimulus-induced activation may be associated with an increased risk for relapse.

PMID- 11515755
TI  - Cytolytic T cells in the immune response to mycobacterium tuberculosis.
AB  - Cytolytic T cells (CTL) are of paramount importance in immune defense against
      tumors and viruses. Work over the past decade has revealed that lysis of infected
      cells is also involved in protective immunity to bacteria and parasites,
      including Mycobacterium tuberculosis. Experiments involving gene-deleted mice and
      the characterization of CTL lines derived from tuberculosis patients suggest an
      important role of CTL in immunity to tuberculosis. More recently, the
      identification of an effector pathway of human CTL provided evidence for direct
      antimicrobial activity of CTL. This pathway involves the combined action of the
      pore-forming perforin and the antibacterial granulysin, both expressed in the
      granules of CTL. Granulysin binds to the bacterial cell surface, thereby
      disrupting the membrane and causing osmotic lysis. The relevance of this pathway
      for protection against intracellular pathogens is suggested by the expression of
      high amounts of granulysin in tissue from patients with tuberculoid leprosy,
      which are able to contain the spread of the bacilli. These findings support the
      current concept of designing novel vaccination strategies which elicit not only
      CD4 + T helper cells, but also CD8 + CTL with direct antibacterial activity.

PMID- 11515756
TI  - Clinical features of tuberculosis among adults in sub-Saharan Africa in the 21st
      century.
AB  - Although tuberculosis was unknown in sub-Saharan Africa before the 19th century,
      rapid spread of infections due to Mycobacterium tuberculosis occurred during the
      20th century and could be found in up to 50% of the adult population by the
      1950s. Owing to changes in age structure, rapid urbanization associated with
      overcrowding living conditions, increasing poverty and the HIV epidemic a 300
      400% increase in tuberculosis cases and deaths has been reported from sub-Saharan
      Africa. Persons dually infected with HIV and tuberculosis may have active
      tuberculosis with typical or atypical clinical features and/or involving multiple
      organ systems. In addition, mycobacteraemia associated with non-specific clinical
      features is common among HIV-infected persons, especially if they are severely
      immunocompromised. Because of the atypical clinical features these patients are
      easily misdiagnosed and are therefore likely to die from what is otherwise a
      curable illness. Consequently there is a need to better characterize the clinical
      features of all forms of tuberculosis, especially in the presence of HIV
      infection.

PMID- 11515757
TI  - Rapid PCR detection of the methicillin resistance gene, mecA, on the hands of
      medical and non-medical personnel and healthy children and on surfaces in a
      neonatal intensive care unit.
AB  - The hands of medical personnel are the chief vectors for transmission of
      antibiotic-resistant bacteria and probably serve as an important reservoir for
      antibiotic resistance genes in hospitals. In this survey we examined different
      reservoirs of the methicillin resistance gene, mecA, using a simplified PCR
      method. Samples (n = 151) were taken from the hands of medical and non-medical
      personnel and healthy children and from surfaces in a neonatal intensive care
      unit (NICU). We also performed sampling from 4 different body sites in 5 of the
      medical personnel. Fifteen out of 16 nurses (94%) from the ICU carried the mecA
      gene on their hands, whereas only 35% of the paediatric nurses were mecA
      positive. Of all medical personnel, 44% carried the mecA gene on their hands.
      There was a significant difference (p < 0.015) between medical and non-medical
      personnel in terms of the carriage rate of mecA. Four samples from surfaces in a
      NICU--2 ventilators, 1 bench and 1 telephone--were positive for mecA. Our results
      are comparable with those from previous studies on reservoirs of methicillin
      resistant coagulase-negative staphylococci using conventional culture techniques.

PMID- 11515758
TI  - Two-stage evaluation and intervention program for control of methicillin
      resistant Staphylococcus aureus in the hospital setting.
AB  - The aim of this study was to develop a 2-stage evaluation and intervention
      program for control of methicillin-resistant Staphylococcus aureus (MRSA) in the
      hospital setting. The first stage included evaluation of MRSA prevalence
      throughout the entire hospital; the presence of MRSA was determined in patients
      or medical staff who had a high risk of carrying it (i.e. as a result of contact
      with surgical wounds). In the second stage, "contact isolation" (which included
      the use of gloves, hand washing before and after treatment of a patient and
      isolation of patients' personal belongings) was carried out in every patient from
      whom MRSA was isolated in 4 intervention departments-Surgery, Orthopaedics,
      General ICU and Neonatal ICU-while the same policy of attempting to isolate MRSA
      was maintained. Both stages lasted 7 months. A comparison between MRSA prevalence
      in the evaluation and intervention stages disclosed a decrease in MRSA isolates
      from 91 to 56 in the entire hospital (p = 0.2) and from 45 to 24 in the
      intervention departments (p = 0.05), respectively; while the number of patients
      with MRSA decreased from 87 to 55 in the entire hospital (p = 0.2) and from 45 to
      18 in the intervention departments (p = 0.007). The number of patients treated
      with vancomycin decreased from 48 before intervention to 23 after "contact
      isolation" was started in the entire hospital (p = 0.02) and from 31 to 5 in the
      intervention departments (p = 0.001). These results provide additional evidence
      in favor of establishing a program to control MRSA spread.

PMID- 11515759
TI  - Rapid detection of the methicillin-resistance gene, mecA, in coagulase-negative
      Staphylococci.
AB  - Phenotypical methods are routinely used to detect methicillin resistance in
      Staphylococci. These methods are time-consuming and there are difficulties in
      detecting all resistant strains carrying the mecA gene. We detected methicillin
      resistant Staphylococci in biological samples by PCR amplification of mecA,
      without the time-consuming step of identifying a bacterial isolate. Methicillin
      resistant Staphylococci isolates were also detected by screening on agar
      supplemented with oxacillin. The biological samples were collected from the hands
      of 17 healthcare workers at the Department of Paediatrics at the University
      Hospital of Tromso. mecA was amplified in 12 of the 17 samples. The gene was
      verified by DNA sequencing of the PCR amplicon. Using the phenotypical method,
      methicillin-resistant Staphylococci were isolated from 6 of the samples. In all 6
      of these samples, mecA was amplified by PCR. We conclude that PCR is a sensitive
      and specific method for detecting methicillin resistance in Staphylococci. The
      PCR detection of mecA is rapid, fairly simple and can easily be assimilated into
      the routines of a clinical microbiological laboratory.

PMID- 11515760
TI  - Bactericidal kinetics of 3 lactoferricins against Staphylococcus aureus and
      Escherichia coli.
AB  - Bovine lactoferricin is an antimicrobial, cationic peptide generated upon gastric
      pepsin cleavage of bovine lactoferrin. We investigated the bactericidal effects
      of native lactoferricin [Lfcin B(17-41)], a shortened derivative [Lfcin B(17-31)]
      and the all-D-amino acid counterpart of Lfcin B(17-31) against Escherichia coli
      and Staphylococcus aureus. The results revealed different activities for the
      peptides against Gram-positive and -negative bacteria. D-Lfcin B(17-31) was the
      most efficient peptide against E. coli. The same peptide showed improved activity
      against S. aureus, D-Lfcin B(17-31) showed a significant better efficacy when
      compared to the L-form, but not when compared to Lfcin B(17-41). There was no
      correlation between the bactericidal concentrations and the time needed to
      achieve maximum effect. This indicates the importance of structural differences
      between the peptides and/or bacteria and implies that the simple thesis of I
      antibacterial target is not valid for lactoferricin.

PMID- 11515761
TI  - Conjugative resistance to tazobactam plus piperacillin among extended-spectrum
      beta-lactamase-producing nosocomial Klebsiella pneumoniae.
AB  - We studied the genetic origins of piperacillin-tazobactam resistance among
      nosocomial Klebsiella pneumoniae strains. A total of 30 nosocomial isolates
      resistant to piperacillin-tazobactam were obtained from various regions of
      Turkey. Isoelectric focusing demonstrated at least 2 enzymes common to all
      strains: I at a pI of 8.0 and the other at 5.4. Piperacillin-tazobactam
      resistance was successfully transferred from all of the strains to Escherichia
      coli. Of the piperacillin-tazobactam-resistant transconjugates, 23 were also
      resistant to ceftazidime. However, 7 transconjugates were susceptible to
      ceftazidime but resistant to piperacillin-tazobactam, producing a single enzyme
      focusing at pI 5.4. Piperacillin resistance caused by this enzyme was reversed by
      clavulanate and by increased amounts of tazobactam, which indicates that this
      enzyme confers resistance due to its high amount. Sequence analysis revealed this
      enzyme to be TEM-1. This study demonstrates that transferable hyper-produced TEM
      1 causes piperacillin-tazobactam resistance in Klebsiella strains in Turkish
      hospitals.

PMID- 11515762
TI  - Unusual antineisserial activity expressed by a systemic isolate of Neisseria
      meningitidis. antimeningococcal effect and properties.
AB  - Antineisserial activity expressed by the systemic Neisseria meningitidis strain
      77/79A was studied using the cross-streaking technique. Of 271 meningococcal
      isolates tested, > 84% were sensitive to this strain. The degree of
      susceptibility was largely dependent upon the agent characteristics of the
      individual isolates. Serogroup A sulfonamide-resistant systemic strains and non
      groupable sulfonamide-sensitive isolates from healthy carriers were highly
      sensitive to the antagonistic activity. Among insensitive or weakly sensitive
      strains, serogroup B sulfonamide-resistant isolates dominated. The activity is of
      general interest as it also antagonized growth of bacteriocin producers.
      Colonization by the producer strain might determine the agent characteristics of
      a surviving population. Group B was predominant among disease-causing strains in
      Norway at the time when strain 77/79A was isolated. A component was purified by
      ammonium sulfate precipitation, gel filtration and hydrophobic interaction
      chromatography. It was bacteriostatic and partly resistant to proteolysis by
      trypsin. Preparations remained active after 30 min at 90 degrees C, but activity
      was lost after 20 min at 120 degrees C. Nevertheless, sodium dodecyl sulfate
      polyacrylamide gel electrophoresis produced a band by Coomassie Brilliant Blue
      staining, corresponding to a molecular mass of approximately 52 kDa. Further
      characterization was limited due to the low levels of active substance produced.

PMID- 11515763
TI  - Clinical and microbiological follow-up of an outbreak of Yersinia
      pseudotuberculosis serotype Ib.
AB  - Yersinia pseudotuberculosis, a food-borne pathogen, causes infection that
      commonly presents as gastroenteritis and mesenteric lymphadenitis. Post
      infectious complications include erythema nodosum, reactive arthritis and, less
      commonly, uveitis and nephritis. Six serotypes of Y. pseudotuberculosis have been
      identified, and post-infectious complications have been identified following
      infection with some, but not all, serotypes. The first recognized outbreak of Y.
      pseudotuberculosis serotype lb occurred in British Columbia in November 1998. We
      documented the incidence of post-infectious complications and the effect of
      antibiotic use on the clinical course. Four months after the outbreak, a
      standardized questionnaire asking about symptoms and antibiotic use was
      administered by telephone to laboratory-confirmed cases. Stool samples were
      collected to examine for chronic carriage of Y. pseudotuberculosis and 59 of 74
      eligible cases participated. The most common post-infectious symptoms were rash
      (8/59) and joint pain (7/59). Microbiological analysis, at follow-up, revealed
      0/36 stools positive for Y. pseudotuberculosis. Seventy-eight percent of cases
      had taken antibiotics during their acute illness. There was no significant
      difference in the frequency of post-infectious symptoms between cases who had or
      had not taken antibiotics. The post-infectious pathogenicity of Y.
      pseudotuberculosis serotype lb is lower than that documented for other serotypes.
      Antibiotic use did not significantly alter the reported clinical course of
      illness.

PMID- 11515764
TI  - Vertebral osteomyelitis in Goteborg, Sweden: a retrospective study of patients
      during 1990-95.
AB  - Vertebral osteomyelitis (VO) is a rare condition and the diagnosis is often
      overlooked initially. Delay in diagnosis may result in vertebral destruction or
      perforation of the spinal canal. We suggest diagnostic criteria in order to
      simplify the diagnosis and classification of VO. Medical records of 58 patients
      with VO from Goteborg during the years 1990-95 were studied retrospectively. The
      incidence, clinical presentation, microbiology and treatment of VO were
      evaluated. The median age at the time of admission was 59 y (range 13-83 y) and
      the male:female ratio was 1.6:1. The incidence was 2.2/100,000 inhabitants/y.
      Sixty-four percent of the patients were natives of Sweden. The patients were
      classified as definite (67%), probable (26%) and possible (7%) VO. Staphylococcus
      aureus was the most common infective agent (34%), followed by Mycobacterium
      tuberculosis (27%). The most common risk factors included recent or current
      infections, immunosuppressive diseases and previous surgery. CRP and ESR were
      elevated in 82% and 88% respectively and plain X-ray changes indicating VO were
      found in 56% of the patients. Radiological changes were found in 34/44 (77%)
      computerized tomography scans and 10/13 (77%) magnetic resonance imaging
      examinations. The median duration of intravenous and oral antibiotic treatment
      were 10 and 179 d respectively. A delay of > I month from the onset of symptoms
      until diagnosis was found in 38% of the patients. This indicates the need for a
      standardized protocol for diagnosing VO. In this paper we suggest diagnostic
      criteria, which have not previously been available.

PMID- 11515765
TI  - Risk factors and prognostic indicators of bacterial meningitis in a cohort of
      3580 postneurosurgical patients.
AB  - In order to identify the incidence, risk factors and prognostic indicators of
      postneurosurgical bacterial meningitis, a 9-y retrospective cohort study was
      performed. The cohort comprised 3580 individuals who underwent neurosurgical
      operations at the Department of Neurosurgery of Catholic University, Rome, a
      1,700-bed university hospital. We observed 52 episodes of postneurosurgical
      meningitis, with infection rates of 1.4/100 patients, 0.8/100 operations for
      craniotomies and 2.6/100 operations for internal cerebrospinal fluid (CSF) shunt
      or ventriculostomy with external drainage. The overall infection rate decreased
      from 2.5/100 operations in 1989 to 0.9/100 in 1997 (p = 0.03). Logistic
      regression analysis indicated that duration of ventriculostomy with external
      drainage [p < 0.01; odds ratio (OR) = 9.67; 95% confidence interval (CI) = 2.44
      38.321 and increasing value of the APACHE III score (p <0.01; OR = 8.51; 95% CI =
      2.15-33.68) were independent risk factors for development of meningitis. The
      overall case fatality rate was 8%. Predictors of mortality were low ( < 1.66
      mmol/l) CSF glucose concentration (p = 0.001), increasing value of the APACHE IIl
      score (p = 0.002) and Gram-negative aetiology (p = 0.003).

PMID- 11515766
TI  - Polymerase chain reaction for diagnosis of cerebral toxoplasmosis in
      cerebrospinal fluid in HIV-positive patients.
AB  - It is important but sometimes difficult to establish a diagnosis of toxoplasma
      encephalitis (TE) in an HIV-positive immunodeficient patient. The most promising
      non-invasive method is polymerase chain reaction (PCR) for Toxoplasma gondii in
      cerebrospinal fluid (CSF). In a retrospective study PCR was used to analyse CSF
      for the presence of T. gondii DNA in 5 HIV-infected patients with a clinical
      suspicion of TE (group 1), 8 patients with other HIV-associated symptoms (group
      2) and 7 other patients with neurological disorders (group 3). PCR was positive
      in 2/4 patients with a final diagnosis of TE and negative in all remaining
      patients in all 3 groups. The 2 patients with positive PCR had a fulminant course
      and experienced treatment failure. The albumin index was elevated in 4/5 patients
      in group 1, of whom 3/4 had a final diagnosis of TE, with suspected TE in 1. This
      small study confirms earlier data indicating that the PCR test has a low
      sensitivity but a high specificity.

PMID- 11515767
TI  - Low baseline antibody level to diphtheria is associated with poor response to
      conjugated pneumococcal vaccine in adults.
AB  - Joining polysaccharide antigens to protein increases immunogenicity in infants.
      In older adults, using conjugation to protein carriers to improve the immune
      response to pneumococcal polysaccharide vaccine has thus far proved
      disappointing. Low immunity to the carrier protein in the elderly may explain the
      failure of conjugated vaccines to elicit a T-cell-dependent response. We
      immunized 49 older adults (ages 60-78) and 50 younger adults (ages 18-45) with
      either 23-valent pneumococcal polysaccharide (PS) vaccine or 5-valent CRM197
      conjugated pneumococcal oligosaccharide. Sera obtained before and after
      vaccination were analyzed for antibody to pneumococcal serotypes 14 and 6B and
      diphtheria toxin by ELISA. Baseline diphtheria toxin antibody level was lower in
      older adults than in younger adults (0.31 and 0.88 IU/ml, respectively; p <
      0.0001). Adults with higher diphtheria antibody level had a higher antibody level
      to PS type 6B after vaccination than those with lower diphtheria antibody level
      (9.9 vs. 3.5 microg/ml, respectively; p = 0.01). Antibody level to PS type 14 was
      higher, but differed by baseline anti-diphtheria antibody level only when the
      older group was evaluated alone. Low levels of antibody to diphtheria protein may
      explain some of the lower responses to conjugate pneumococcal vaccine in older
      adults.

PMID- 11515768
TI  - Immunogenicity and reactogenicity of a new measles, mumps and rubella vaccine
      when administered as a second dose at 12 y of age.
AB  - An open randomized trial involving 301 subjects was conducted in order to compare
      the reactogenicity and immunogenicity of a new measles, mumps and rubella (MMR)
      vaccine, SB MMR, with those of a commercial MMR vaccine, Merck MMR, when given as
      a second dose to children at 11-12 y of age. All subjects had previously received
      Merck MMR in the first year of life. In initially seronegative subjects, all
      subjects receiving the Merck MMR vaccine had seroconverted with respect to
      measles (10/10 subjects), mumps (38/38) and rubella (4/4). Of the subjects
      receiving SB MMR, 6/7 seroconverted with respect to measles, 29/31 with respect
      to mumps and 3/3 with respect to rubella. No difference was seen in
      seroconversion rates or geometric mean values (GMVs) between groups. In initially
      seropositive subjects, a higher anti-mumps immune response rate was observed in
      the SB MMR group (59.3%) compared with the Merck MMR group (24.1%). Higher post
      vaccination anti-mumps and anti-rubella GMVs were observed in the group receiving
      SB MMR (p < 0.007), whereas higher anti-measles GMVs were observed in the Merck
      MMR group (p = 0.0013). There was a lower (p = 0.013) incidence of pain at the
      injection site in subjects receiving SB MMR (20.1%) compared with Merck MMR
      (33.3%). Incidences of systemic reactions were similar between groups.

PMID- 11515769
TI  - Splenic infarct during infectious mononucleosis.
AB  - We present a case of splenic infarct during infectious mononucleosis in a 17-y
      old boy. The patient's condition improved without the need for surgery.

PMID- 11515770
TI  - Intra-abdominal actinomycosis with hepatic pseudotumor and xanthogranulomatous
      pyelonephritis in a 6-y-old boy.
AB  - We report the case of a 6-y-old boy with actinomycosis, presenting as
      xanthogranulomatous pyelonephritis (XGP), hepatic pseudotumor and abdominal
      abscess. Symptoms included intermittent fever, abdominal pain and significant
      weight loss. Hepatic and renal tumor masses were suspected on sonography and
      computerized tomography. XGP and actinomycosis were proven by pathology. The
      patient recovered well with antibiotic alone.

PMID- 11515771
TI  - Fatal septicemia and meningitis due to Morganella morganii in a patient with
      Hodgkin's disease.
AB  - A unique case of spontaneous Morganella morganii meningitis in a patient with
      stage IV Hodgkin's disease, following hematogenous spread from the urinary tract,
      is described. Late initiation of appropriate antibiotic treatment was probably
      responsible for the fatal outcome. This case illustrates the pathogenic potential
      of M. morganii in immunocompromised hosts.

PMID- 11515772
TI  - Advanced peritonitis and subclinical disseminated intravascular coagulopathy
      associated with Chlamydia trachomatis infection.
AB  - A 29-y-old woman was admitted to our hospital complaining of slight fullness of
      the lower abdomen. Ultrasound echographic study and magnetic resonance imaging
      showed pleural effusion and pelvic ascites. Laboratory investigation revealed
      anemia and thrombocytopenia (hemoglobin 6 mmol/l; platelets 7 x 10(10)/l),
      remarkable polyclonal hypergammopathy (gamma immunoglobulin 7.7 g/dl) and
      subclinical disseminated intravascular coagulopathy (DIC). By laparoscopy,
      extensive adhesion of the peritoneum and bilateral ovarian tubes was observed.
      From the appearance of adhesion, we suspected Chlamydia trachomatis infection and
      performed serologic and molecular studies. Administration of clarithromycin
      resolved hypergammopathy, DIC and ascites.

PMID- 11515773
TI  - Clinical and laboratory signs of mitochondrial dysfunction secondary to
      nucleoside analogue antiretroviral therapy are reversible.
AB  - During 27 months treatment with 400 mg didanosine and 80 mg stavudine daily but
      no protease inhibitor therapy, a 50-y-old HIV-positive woman gradually lost 13 kg
      in weight, her arms, legs and buttocks decreased in volume and she experienced
      fatigue and polyneuropathy. Laboratory tests showed slight increases in plasma
      lactate and liver enzyme levels. Eighteen months after withdrawal of
      antiretroviral drug, the patient was free of fatigue and polyneuropathy and had
      regained 7 kg in weight as well as most of the volume of her arms, legs and
      buttocks.

PMID- 11515774
TI  - Incidence of gynecomastia in men infected with HIV and treated with highly active
      antiretroviral therapy.
AB  - A longitudinal study found that the incidence of gynecomastia in HIV-infected
      male patients treated with highly active antiretroviral therapy was 0.8/100
      patient-years, with a prevalence of 2.8% in those treated for > or = 2 y. Even
      though the physiopathology remains unclear, this study suggests that gynecomastia
      should be monitored in these patients.

PMID- 11515775
TI  - An unusual ECG after spinal surgery.

PMID- 11515776
TI  - Treatment strategies for bronchial asthma: an update.
AB  - Advances in understanding the biomolecular basis of the disease's inflammatory
      and remodeling responses are offering new therapeutic choices--and sometimes new
      drug-delivery systems--in categories such as beta-agonists, glucocorticoids, and
      leukotriene blockers. Meanwhile, researchers are exploring novel targets,
      including intercellular signals and cell-adhesion and gene-activating molecules.

PMID- 11515777
TI  - Erectile dysfunction and cardiovascular risk factors.
AB  - Erectile dysfunction (ED) affects as many as 30 million men in the United States.
      Its risk factors are similar to those for atherosclerotic heart disease.
      Physicians should ask male patients--particularly those with cardiovascular
      disease--about ED and men with confirmed ED about cardiovascular risk factors.
      Oral sildenafil is an effective therapy for both organic and psychogenic ED; it
      is contraindicated in patients taking organic nitrates.

PMID- 11515778
TI  - Medicinal herbs: answers and advice, Part 2.
AB  - Herbal medicines typically contain a number of active components. As a result,
      some provide multiple benefits and some a mixture of benefits and adverse
      effects. Hawthorn, kava, and saw palmetto fall into the first category and
      licorice into the second. The problems with licorice can be largely avoided by
      using a deglycyrrhizinated preparation.

PMID- 11515779
TI  - A loss of literacy? A century of changing substance and style in medical book
      reviewing.

PMID- 11515780
TI  - Evolution from pretangle neurons to neurofibrillary tangles monitored by thiazin
      red combined with Gallyas method and double immunofluorescence.
AB  - Double immunofluorescence for paired helical filament (PHF)-tau (AT8) and
      ubiquitin, enhanced by catalyzed reporter deposition amplification, was combined
      with thiazin red (TR), a fluorochrome, which has an affinity to fibrillary
      structures such as neurofibrillary tangles (NFTs). After recording these triple
      fluorescent images, sections were subjected to the Gallyas silver impregnation
      method, so that four different staining properties could be compared on the same
      structure. Among pyramidal neurons quantified in the hippocampus from six cases
      of Alzheimer's disease, 60.3% were positive for ubiquitin, and were consistently
      positive for TR. TR-positive neurons (77.1%) harbored fibrillary structures in
      the cytoplasm and were always positive for the Gallyas stain, which stained the
      largest number of legions (94.5%). AT8-positive neurons without fibrillary
      structure were negative for TR (11.6%, pretangle neurons). Some of the pretangle
      neurons were positive for the Gallyas stain even without fibrillary structures.
      Appearance of TR stain and ubiquitin in NFTs, but not in pretangle neurons,
      suggests that ubiquitin is integrated into tau-positive neurons after their
      transformation into NFTs. Because TR-positive NFTs sometimes lacked ubiquitin
      like immunoreactivity, involvement of ubiquitin may not be an early event during
      NFT formation. This combined method is now found useful in determining how
      molecules other than tau are involved during the evolution from tau-positive
      neurons to NFTs in various neurological disorders characterized by the deposition
      of tau.

PMID- 11515781
TI  - Molecular properties and gene expression of albumin in the skeletal muscle
      following hindlimb immobilization in a shortened position.
AB  - We investigated the effect of immobilization of hindlimb in a shortened position
      on proteins in the mouse soleus muscle and determined the molecular properties of
      a protein that had changed specifically in the atrophied muscle. A protein of
      67.5 kDa was increased significantly (P<0.001) by 1.9-fold in the atrophied
      muscle compared to the control muscle as shown by sodium dodecyl sulfate
      polyacrylamide (SDS-PAGE). The isoelectric point of the protein was pH 6.3 in two
      dimensional PAGE. We carried out N-terminal and peptide mapping analyses to
      identify the primary structure of the protein. A 17-amino acid sequence showed
      100% homology with the mouse serum albumin precursor. A peptide map of the 67.5
      kDa protein was similar to that of mouse serum albumin. Mass spectrometry also
      showed the protein to be most similar to mouse serum albumin. Thus, based on
      these criteria, the 67.5-kDa protein was indistinguishable from mouse serum
      albumin. An immunohistochemical study showed that the 67.5-kDa protein was
      located mainly in the endomysium of the control muscle and had accumulated in the
      widened interstitial spaces of the atrophied muscle. A reverse transcription-PCR
      assay revealed that the albumin gene was expressed in skeletal muscle tissue, but
      that its expression was significantly lower in the atrophied muscle than in the
      control muscle (P<0.001). We conclude that albumin is increased in atrophied
      muscle and suggest that this may be of clinical importance for analyzing the
      process of muscular atrophy.

PMID- 11515782
TI  - Tangle-bearing neurons contain more free cholesterol than adjacent tangle-free
      neurons.
AB  - Neurofibrillary tangles are seen both in senile dementia of Alzheimer's disease
      and in juvenile dementia of Niemann-Pick type C disease. Apolipoprotein E is a
      main cholesterol transport molecule in brain. In Alzheimer's disease, possession
      of the apolipoprotein E epsilon4 allele is associated with an earlier onset in
      tangle formation and an increased tangle load. Niemann-Pick type C disease is a
      disorder with elevated intracellular levels of free cholesterol due to a genetic
      deficit in its transport. The link between tangle formation and cholesterol
      metabolism in both diseases suggests that alterations of intracellular free
      cholesterol levels could influence tangle formation. Using semiquantitative
      fluorescence microscopy with the free cholesterol probe filipin and analysing 939
      neurons, we observed that mean levels of free cholesterol in tangle-bearing
      neurons were higher than those of adjacent tangle-free neurons.

PMID- 11515783
TI  - The autonomic higher order processing nuclei of the lower brain stem are among
      the early targets of the Alzheimer's disease-related cytoskeletal pathology.
AB  - The nuclei of the pontine parabrachial region (medial parabrachial nucleus, MPB;
      lateral parabrachial nucleus, LPB; subpeduncular nucleus, SPP) together with the
      intermediate zone of the medullary reticular formation (IRZ) are pivotal relay
      stations within central autonomic regulatory feedback systems. This study was
      undertaken to investigate the evolution of the Alzheimer's disease-related
      cytoskeletal pathology in these four sites of the lower brain stem. We examined
      the MPB, LPB, SPP and IRZ in 27 autopsy cases and classified the cortical
      Alzheimer-related cytoskeletal anomalies according to an established staging
      system (neurofibrillary tangle/neuropil threads [NFT/NT] stages I-VI). The
      lesions were visualized either with the antibody AT8, which is immunospecific for
      the abnormally phosphorylated form of the cytoskeletal protein tau, or with a
      modified Gallyas silver iodide stain. The MPB, SPB, and IRZ display cytoskeletal
      pathology in stage I and the LPB in stage II, whereby bothstages correspond to
      the preclinical phase of Alzheimer's disease (AD). In stages III-IV (incipient
      AD), the MPB and SPP are severely affected. In all of the stage III-IV cases, the
      lesions in the LPB and IRZ are well developed. In stages V and VI (clinical phase
      of AD), the MPB and SPP are filled with the abnormal intraneuronal material. At
      stages V-VI, the LPB is moderately involved and the IRZ shows severe damage. The
      pathogenesis of the AD-related cytoskeletal lesions in the nuclei of the pontine
      parabrachial region and in the IRZ conforms with the cortical NFT/NT staging
      sequence I-VI. In the event that the cytoskeletal pathology observed in this
      study impairs the function of the nerve cells involved, it is conceivable that
      autonomic mechanisms progressively deteriorate with advancing cortical NFT/NT
      stages. This relationship remains to be established, but it could provide
      insights into the illusive correlation between the AD-related cytoskeletal
      pathology and the function of affected neurons.

PMID- 11515784
TI  - Differential activation of microglial cells in local and remote areas of IRBP1169
      1191-induced rat uveitis.
AB  - Using a Lewis rat model of interphotoreceptor retinoid binding protein (IRBP)
      induced experimental autoimmune uveitis (EAU) we examined cellular reactions in
      the optic pathway (retina, choroid, optic nerve, optic tract, colliculus
      superior, and visual cortex). Two to six animals were studied at days 0, 7, 9,
      11, 12, 13, 14, 18 and 22 after immunization by immunohistochemistry with
      monoclonal antibodies against ED , ED2, OX6, OX22, EMAP II, AIF-1 and W3/13. In
      the retina, choroid and distal optic nerve increased immunoreactivity to ED1,
      OX6, OX22, EMAP II, AIF-1 and W3/13 was initially observed at day 9, peaked at
      days 13-14 and diminished rapidly from day 18 onwards. No changes were seen in
      the density of ED2-positive resident macrophages. In the optic tract, ED1 and OX6
      expression was induced in microglial cells beginning with day 11 and persisted
      until day 22. AIF-1, EMAP II and ED2 expression was not visibly up-regulated and
      no lymphocytic infiltrates (OX22-, W3/13-positive cells) were observed. In the
      central projection fields, no cellular reaction could be found. Thus, cellular
      response in IRBP-induced rat uveoretinitis is not restricted to the eye.
      Microglial activation is also seen in the distal optic nerve and optic tract.
      This remote microglial activation, however, differs in intensity, time course and
      expression of activation markers, thus indicating different activation cascades.
      The mild remote microglial activation is probably due to neuronal-microglial
      interactions resulting from neuronal damage in the retinal ganglion cell layer
      and nerve fiber layer with consecutive axonal degeneration and not from an
      inflammatory reaction as seen in the eye.

PMID- 11515785
TI  - Immunolocalization of FAS and FAS ligand in inflammatory myopathies.
AB  - Fas/Fas ligand (FasL) interaction can induce apoptosis, have a costimulatory role
      or act as a mechanism by which cytotoxic T cells produce target cell lysis. We
      used several commercially available antibodies to study Fas and FasL expression
      in polymyositis (PM), inclusion body myositis (IBM), dermatomyositis (DM) and
      normal controls. A strong Fas signal occurred on the sarcolemma, and to a lesser
      extent in the sarcoplasm of neural cell adhesion molecule (NCAM)-positive or
      developmental myosin heavy chain-positive regenerating muscle fibers and of
      injured fibers with presumed abortive regenerative activity, including some
      nonnecrotic invaded fibers in PM and IBM and some of the atrophic perifascicular
      fibers in DM. Most fibers within groups of atrophic fibers in IBM were strongly
      Fas-positive, and statistically more muscle fibers were Fas-positive in IBM
      compared to PM. A subset of the actively invading CD8+ T cells in nonnecrotic
      muscle fibers in PM and IBM, and scattered CD4+ cells in each inflammatory
      myopathy, had up-regulated Fas expression, probably reflecting costimulation. No
      FasL antibody consistently labeled the positive control tissue (testis) or
      intramuscular elements in control or inflammatory myopathy specimens. Our study
      identifies regenerating muscle fibers as the main site of Fas immunoreactivity in
      inflammatory myopathies, and Fas expression may be part of an activated or
      reactivated developmental program of new gene expression in regenerating or
      denervated muscle fibers. Our data plead against a specific role of Fas/FasL
      interaction in the immunopathogenesis of the inflammatory myopathies.

PMID- 11515786
TI  - Expression of the lysosome-associated membrane proteins in myopathies with rimmed
      vacuoles.
AB  - Lysosome-associated membrane proteins (LAMPs) are structural glycoproteins
      located on the lysosomal membrane and are thought to have an important role in
      protein degradation. Increased lysosomal activity is associated with the
      formation of rimmed vacuoles, which are observed in various muscle disorders such
      as inclusion body myositis (IBM) and distal myopathy with rimmed vacuole (DMRV).
      In the present study, we examined LAMP-1 and LAMP-2 in biopsied muscle specimens
      from four cases of sporadic IBM and two of DMRV, as well as six of myopathies
      without rimmed vacuoles. In all cases of IBM and DMRV, immunohistochemistry
      showed accumulation of LAMPs in the rimmed vacuoles and the subsarcolemmal
      portion of the vacuolated fibers. Immunoreactivities of LAMPs in the vacuolated
      fibers were often associated with those of cathepsin D; however, cathepsin D was
      not expressed on some LAMP-positive fibers. Further, atrophic muscle fibers were
      sometimes positive for LAMPs expression. These findings were more prominent in
      LAMP-2 than in LAMP-1. Thus, LAMP-2 may play an important role in the increased
      protein degradation in diseased muscle fibers. The increased expression of LAMPs
      in the vacuolated muscle fibers may be associated with the formation of rimmed
      vacuoles in IBM and DMRV.

PMID- 11515787
TI  - Fibrillar amyloid-beta affects neurofibrillary changes but only in neurons
      already involved in neurofibrillary degeneration.
AB  - The aim of this study of the cerebral cortex of 8 non-demented elderly subjects
      and of 17 subjects in the severe stage of Alzheimer's disease (AD) (Global
      Deterioration Scale stage 7/Functional Assessment Staging procedure stage 7a-f)
      was to examine the relationships between amyloid-beta (Abeta) deposits and
      neurofibrillary degeneration. The study shows that neuronal processes with
      neurofibrillary changes are detectable in only a minority of fibrillar plaques:
      from 31% to 49% of fibrillar plaques within frontal, temporal, parietal, limbic,
      occipital, and insular cortices. The correlations observed between the numerical
      densities of neurons with neurofibrillary tangles (NFTs) and the densities of
      Thioflavin-S-positive fibrillar plaques with neurofibrillary changes (r=0.61;
      P<0.01) indicate that neurofibrillary pathology in neocortical plaques reflects
      the topography and rate of neurofibrillary changes in neocortical neurons. The
      accumulation of abnormally phosphorylated tau in only some plaques indicates that
      fibrillar Abeta enhances paired helical filament accumulation locally only in
      dystrophic neurites already involved in neurofibrillary degeneration. The lack of
      correlation between the number of neurons with neurofibrillary changes and the
      number of all Thioflavin-S-positive fibrillar plaques (with and without
      neurofibrillary changes) suggests that beta-amyloidosis does not contribute to
      initiation of neurofibrillary degeneration in neurons.

PMID- 11515788
TI  - Changes of skeletal muscle in young dystrophin-deficient cats: a morphological
      and morphometric study.
AB  - Dystrophin deficiency causes Duchenne muscular dystrophy (DMD). Hypertrophic
      feline muscular dystrophy (HFMD) is a homologous animal model of DMD. Our
      objective was to investigate the early changes caused by dystrophin deficiency in
      skeletal muscle of cats of 3-4 and 6-9 months. Obvious histological lesions were
      already present in the younger cats, and they increased in magnitude over time.
      They consisted of multifocal areas of degeneration and regeneration with
      mononuclear infiltration, and a wide variation in myofiber diameter, as evidenced
      by significantly increased variability coefficients in muscle fiber size,
      myofiber splitting, central nuclei, and hypercontracted myofibers. Widespread
      multifocal mineralizations were frequently observed. Endomysial and perimysial
      fibrosis was not a feature observed in axial or appendicular muscles, but was
      present in the diaphragm of two cats at necropsy. There was a significant
      decrease in the number of type 2A myofibers in dystrophin-deficient cats at both
      ages. Sarcolemmal dystrophin was mostly absent in all dystrophin-deficient cats;
      however, a small percentage of fibers stained positive, accounting for a faint
      residual band in the immunoblot. Carrier females had a mosaic staining pattern
      with irregular staining in most fibers, or even absent staining in rare fibers.
      However, no histological lesions were seen. Taken together, these data provide
      significant baseline information for further studies on the early changes
      associated with dystrophin deficiency in cats, or use of young dystrophin
      deficient cats in therapeutic trials.

PMID- 11515789
TI  - Coronaviruses in brain tissue from patients with multiple sclerosis.
AB  - Brain tissue from 25 patients with clinically definite multiple sclerosis (MS)
      and as controls brain tissue from 36 patients without neurological disease was
      tested for the presence of human coronaviral RNA. Four PCR assays with primers
      specific for N-protein of human coronavirus strain 229E and three PCR assays with
      primers specific for the nucleocapsid protein of human coronavirus strain OC43
      were performed. Sporadic positive PCR assays were observed in both patients and
      controls in some of the PCR assays. However, these results were not reproducible
      and there was no difference in the proportion of positive signals from the MS
      patients compared to controls. Evidence for a chronic infection with the human
      coronaviruses strain 229E or OC43 in brain tissue from patients with MS or
      controls has not been found in this study.

PMID- 11515790
TI  - Glioblastoma-related gene mutations and over-expression of functional epidermal
      growth factor receptors in SKMG-3 glioma cells.
AB  - Amplification of the epidermal growth factor receptor (EGFR) gene is found in
      about 40% of glioblastomas (GBMs) but is rarely detected in GBM cell lines. We
      confirmed that the exceptional SKMG-3 GBM cell line retained amplified EGFR genes
      in vitro, and found that these sequences were concentrated on extra-chromosomal
      DNA particles similar to double-minute chromosomes. The cells contained two other
      gene mutations that are associated with high-grade astrocytic tumors: extra
      chromosomal amplification of the cyclin-dependent kinase-4 (CDK4) gene and a
      homozygous mutation within the PTEN tumor suppressor gene. Immunoblots revealed
      very high levels of EGFR, moderately increased expression of CDK4, and no
      detectable PTEN protein. The overexpressed SKMG-3 EGFRs responded to exogenous
      ligand and resembled normal rather than mutant receptors. A heterozygous mutation
      of the p53 gene (p53R282W) correlated with failure of radiation to induce the
      expression of cyclin-dependent kinase inhibitor p21waf1 or an early G1 cell cycle
      arrest. Although each of these gene mutations occurs in GBMs, SKMG-3 cells had an
      unusual genotype in that a p53 gene mutation co-existed with amplified EGFR
      genes. Nonetheless, the SKMG-3 cell line can be exploited as a model to study how
      oncogenic EGFR signals in GBM cells interact with over-expressed CDK4 and loss of
      PTEN to confer the malignant phenotype.

PMID- 11515791
TI  - Relationship between DNA fragmentation, morphological changes and neuronal loss
      in Alzheimer's disease and dementia with Lewy bodies.
AB  - This aim of the present study was to identify whether apoptotic features relate
      to the degree of cortical neuronal loss in cases with variable cortical
      degeneration. Neuronal apoptosis was assessed using histochemical and
      morphological criteria in cases with Alzheimer's disease (AD, n=7) or Lewy bodies
      (n= 11) compared with controls (n=11). AD cases had both significant plaque and
      tangle formation but no Lewy bodies, while cases with Lewy bodies had significant
      plaque formation but no tangles. Cortical sections were stained using (TdT)
      mediated UTP nick end labelling (TUNEL), propidium iodide, and cell and pathology
      specific labels. Cells identified as non-neuronal were excluded. Large cortical
      nuclei were classified as abnormal if they were TUNEL-positive with DNA
      condensation across the nucleus and no visible nucleolus, and further subdivided
      according to the presence or absence of visible neuronal cytoplasm. Nuclei were
      considered morphologically normal regardless of TUNEL staining if they possessed
      a clear nucleolus. Cortical fields containing the greatest density of TUNEL
      positive nuclei were regionally sampled and the proportion of all classified
      nuclei calculated. Analysis of variance was used to identify any significant
      relationships. Only AD cases had significant numbers of abnormal nuclei (23+/-6%,
      P=0.002) and a corresponding decrease in normal neurons (28+/-7% loss, P= 0.004).
      Absolute neuronal density was also decreased in AD (AD density 64+/-11% of other
      cases, P=0.02). Abnormal nuclei were not associated with plaque or tangle
      pathology. Our results suggest that nuclear abnormalities appear restricted to AD
      cases with substantial tau deposition and are related to the degree of neuronal
      degeneration.

PMID- 11515792
TI  - Atypical amyotrophic lateral sclerosis with dementia mimicking frontal Pick's
      disease: a report of an autopsy case with a clinical course of 15 years.
AB  - This report concerns an autopsy case of atypical amyotrophic lateral sclerosis
      (ALS) with dementia mimicking frontal Pick's disease. The patient was a Japanese
      woman without hereditary burden who was 45 years old at the time of death. She
      developed abnormal behavior and amnesia at age 30, followed by disinhibition,
      aspontaneity, urinary incontinence, abulia, and rectal incontinence. Neurological
      signs compatible with ALS developed about 14 years after the disease onset. No
      respirator was used throughout the clinical course. Macroscopically,
      neuropathological examination showed atrophy of the frontotemporal lobes with
      accentuation in the convexities of the frontal lobes. Histologically, there was
      neuronal loss in the cerebral cortex, parahippocampal gyrus, amygdala, caudate
      nucleus, substantia nigra, brain stem motor nuclei, and anterior horns of the
      spinal cord, in addition to marked degeneration of the pyramidal tracts.
      Ubiquitin-immunoreactive neuronal inclusions were present in the frontotemporal
      cortical layer II neurons and motor neurons in the brain stem and spinal cord. In
      the hippocampal dentate granular cells, many ubiquitin-immunoreactive neurites
      were present without ubiquitin-immunoreactive intraneuronal inclusions. Based on
      these clinicopathological findings and a review of the literature, we concluded
      that our case was atypical ALS with dementia of long disease duration. We also
      note the possibility that motor neuron disease-inclusion dementia with a long
      clinical course may develop into ALS in the final stage of the illness.

PMID- 11515793
TI  - Severe lymphocytic adenohypophysitis with selective disappearance of prolactin
      cells: a histologic, ultrastructural and immunoelectron microscopic study.
AB  - We report the first documented example (case 1) of lymphocytic adenohypophysitis
      (LAH) associated with selective destruction of prolactin cells. The morphologic
      data are compared to those obtained in another, more typical case (case 2). Case
      1 was a 35-year-old woman with remote history of pregnancy who presented with
      headache, oligomenorrhea and visual disturbances. The blood prolactin level was
      nearly undetectable, but no deficiency of other pituitary hormones was evident. A
      sellar and parasellar mass compressing the optic chiasm was removed
      transsphenoidally. Histology demonstrated massive infiltration with lymphocytes,
      plasma cells and macrophages causing marked destruction of pituitary acini. Part
      of the gland was fibrotic. Immunocytochemistry documented all pituitary hormones,
      but only few cells, probably mammosomatotrophs, were immunoreactive for
      prolactin. Electron microscopy and immunoelectron microscopy using double gold
      labeling for growth hormone and prolactin detected no prolactin cells. A striking
      ultrastructural finding was the prominence of folliculostellate cells in areas of
      active cell destruction supporting the presumed immune role of these cells. LAH
      in case 2 (24-year-old woman) became manifest during late pregnancy, causing
      pituitary enlargement and visual field defects. Pituitary tests showed no major
      hormonal deficits. Moderate hyperprolactinemia was appropriate for her pregnancy
      status. A sellar mass, thought to be adenoma, was removed. Histology demonstrated
      multifocal LAH without major destruction of acinar structures.
      Immunocytochemistry and electron microscopy documented all pituitary cell types
      including the marked abundance of prolactin-producing cells, resultant of
      gestational prolactin cell hyperplasia. In addition to prolactin cells and growth
      hormone cells, immunoelectron microscopy showed several bihormonal
      mammosomatotrophs, also appropriate for pregnancy.

PMID- 11515794
TI  - Characterization of vagal input to the rat esophageal muscle.
AB  - There is recent morphological evidence for an interaction of autonomic nerve
      fibers and extrinsic motor nerves of the rat esophagus. The aim of the present
      study was to investigate a possible functional role of this autonomic innervation
      of vagal motor fibers on rat esophageal smooth and striated muscle function in
      vitro. The entire esophagus with both Nn vagi, including the Nn recurrentes, was
      dissected and placed in an organ bath with oxygenated Krebs-Ringer buffer.
      Contractile activity was measured in longitudinal direction with a force
      transducer. Both Nn vagi were placed on a bipolar platinum electrode 2 cm apart
      from the esophagus. Vagal stimulation, applied for 1 s (40 V, 0.5 ms, 20 Hz)
      resulted in a biphasic contractile response, which was completely blocked by
      tetrodotoxin (10(-6) M). The first part consisted of a tetanic striated muscle
      contraction, which was abolished by tubocurarin (10(-5) M) but unaffected by
      atropine (10(-6) M) or hexamethonium (10(-4) M). In contrast, the second part was
      completely abolished by hexamethonium (10(-4) M) and atropine (10(-6) M), whereas
      tubocurarine (10(-5) M) showed no influence, suggesting a stimulation of
      preganglionic nerve fibers supplying esophageal smooth muscle (muscularis
      mucosae). In order to characterize possible autonomic transmitters of the ENS of
      the esophagus, the following experiments were carried out. The magnitude of the
      striated muscle response was unaffected by VIP (10(-7) M), 5-HT (10(-6) M) and
      galanin (10(-8) - 10(-7) M), whereas they caused an inhibition of the smooth
      muscle response (VIP: -53.8 +/- 4.2%; galanin 10(-8) M: - 18.5 +/- 2.2%; 10(-7)
      M: -40.4 +/- 2.9%; 5-HT: -78.2 +/- 2.1%). The inhibitory effects of VIP and
      galanin on smooth muscle were reversible by the antagonists VIP 10-28 and galanin
      1-15. In the presence of the nitric oxide synthase (NOS) inhibitor L-NNA (10(-4)
      M), the smooth and striated muscle contraction were not significantly influenced.
      Exogenous application of the NO-donor DEA-NO (10(-4) M) reduced the smooth muscle
      contraction by -81.6 +/- 7.4%, but had no significant effect on the striated
      muscle contraction. Though immunohistochemical findings are highly suggestive of
      an nitrergic autonomic modulation of striated muscle contraction by enteric
      neurons, we could not demonstrate a NO-mediated action on striated muscle
      activity. Therefore, the physiological relevance of the immunohistochemical
      findings remain unclear.

PMID- 11515795
TI  - Effect of parasympathetic decentralization on interferon-gamma release from rat
      submandibular lymph nodes in vitro.
AB  - The aim of this study was to examine the regulation of interferon (IFN)-gamma
      release by cells from submandibular lymph nodes of rats subjected to a unilateral
      parasympathetic decentralization by severing the ipsilateral chorda tympani 7
      days earlier. Cells obtained from contralateral sham-operated submandibular lymph
      nodes were employed as control. Parasympathetic decentralization of lymph nodes
      resulted in significantly less IFN-gamma release as compared to that found in
      innervated lymph nodes. Mitogens (lipopolysaccharide, concanavalin A) stimulated
      IFN-gamma release in cells derived from the innervated lymph nodes only. The
      muscarinic agonist metacholine decreased IFN-gamma release in cells derived from
      innervated lymph nodes. At the highest concentration employed (10(-4) M),
      metacholine suppressed the stimulatory effect of mitogens on IFN-gamma release in
      cells of innervated lymph nodes while the muscarinic antagonist atropine (10(-8) 
      10(-4) M) lacked to affect IFN-gamma release. Addition of nicotine (10(-5) - 10(
      3) M) failed to modify IFN-gamma release. The results support the occurrence of
      significant effects of local parasympathetics in modulating IFN-gamma release by
      submandibular lymph nodes.

PMID- 11515797
TI  - Developmental changes in heme-oxygenase-2 and bNOS expression in enteric neurons
      in the pig duodenum.
AB  - There exists much parallelism between carbon monoxide- and nitric oxide
      generating systems. Therefore, we wondered whether developmental and functional
      differences along the duodenum similarly affect, part of them, namely, heme
      oxygenase-2-(HO-2) and neural isoform of nitric oxide synthase- (nNOS) expressing
      neurons. By applying NADPH diaphorase histochemistry and HO-2
      immunohistochemistry on whole-mount preparations and by using stereologic
      methods, a qualitative and quantitative description of HO-2 and nNOS expression
      was obtained. Examinations were carried out on the duodenum of fetal, neonatal
      and weaned pigs. At all ages, three enteric plexuses were readily distinguished.
      The presence of both enzymes fits in with other morphological and physiological
      reports. However, the expression of both enzymes significantly changed during
      development. The number of HO-2-IR neurons increased approximately 20-fold in the
      inner submucous and almost doubled in the myenteric plexus. In addition, the
      number of nNOS-expressing neurons displayed a significant decrease in the outer
      submucous plexus after weaning. High levels of glucocorticoids may cause the
      perinatally increased HO-2 expression, whereas an influence on nNOS expression is
      doubtful. Therefore, it seems that notwithstanding the high similarity between
      both systems, their expression is regulated differently in the pig duodenum.

PMID- 11515796
TI  - Hemorrhage activates catecholaminergic neurons sensitive to GABA in the nucleus
      of the solitary tract with ascending projections to the subfornical organ in
      rats.
AB  - The activity of neurons in the region of the nucleus of the solitary tract (NTS)
      that were antidromically identified by electrical stimulation of the rat
      subfornical organ (SFO) was tested for a response to microiontophoretic
      application of gamma-aminobutyric acid (GABA), hemorrhage (10 ml/kg b.w.t.), or
      local administration of the chemical neurotoxin, 6-hydroxydopamine (6-OHDA), into
      the SFO stimulation site. Microiontophoretically (MIPh) applied GABA caused a
      decrease excitability in 22 out of 24 neurons tested, and the inhibition was
      blocked by MIPh-applied bicuculline, a GABAA antagonist, but not by phaclofen, a
      GABAB antagonist. Of these neurons that responded to GABA, 17 displayed an
      increase in neural firing in response to hemorrhage, while 5 were unresponsive.
      The occurrence of both antidromic spikes and post-stimulus inhibition of 9 out of
      13 neurons tested was completely abolished by the injection of 6-OHDA into the
      SFO. These results suggest that neurons in the region of the NTS, which carry
      peripheral baroreceptor information to the SFO, receive GABAergic inhibitory
      inputs via a GABAA receptor mechanism, and imply that part of these neurons are
      catecholaminergic.

PMID- 11515798
TI  - Pressor response to unilateral carotid chemoreceptor activation is not affected
      by ipsilateral antagonism of excitatory amino acid receptors in the rostral
      ventrolateral medulla of awake rats.
AB  - The importance of the integrity of the ipsilateral rostral ventrolateral medulla
      (RVLM) in the pressor response to activation of unilateral arterial
      chemoreceptors was evaluated. To achieve this goal, the left carotid body artery
      was ligated prior to the experiment and a guide cannula was implanted in the
      direction of the right RLVM, i.e. the side where the carotid body artery was kept
      intact. On the day of the experiment, the chemoreflex was activated with
      potassium cyanide (KCN, i.v.) before and after unilateral microinjection of
      kynurenic acid into the rostral or caudal aspect of the RVLM. The data indicated
      that microinjection of kynurenic into the rostral or caudal aspect of the RVLM
      produced no effect on the pressor response of chemoreflex activation. These data
      suggest that chemoreflex activation excites a neuronal network in which the
      processing of the sympatho-excitatory component of the chemoreflex is not
      restricted to an excitatory projection from the nucleus tractus solitarii to the
      ipsilateral RVLM.

PMID- 11515799
TI  - Moxonidine reduces pilocarpine-induced salivation in rats.
AB  - Cholinergic agonists activate salivation and the alpha2-adrenergic and
      imidazoline receptor agonists induce opposite effects. In the present study, we
      investigated the effects of intracerebroventricular (i.c.v.) or intraperitoneal
      (i.p.) injection of moxonidine (an alpha2-adrenergic and imidazoline receptor
      agonist) on the salivation induced by the cholinergic agonist pilocarpine. Male
      Holtzman rats with stainless steel cannula implanted into the lateral ventricle
      (LV) were used. In rats anesthetized with tribromoethanol (200 mg kg(-1), saliva
      was collected using pre-weighed small cotton balls inserted in the animal's
      mouth. The treatment with moxonidine (5, 10 and 20 nmol in 1 microl) injected
      i.c.v. reduced the salivation induced by pilocarpine (1 mg kg(-1)) injected i.p.
      (48 +/- 5, 17 +/- 2 and 15 +/- 2 mg min(-1) vs. control, 73 +/- 7 mg min(-1)).
      The same doses of moxonidine injected i.c.v. also reduced the salivary secretion
      induced by pilocarpine (500 nmol in 1 microl) injected i.c.v. (44 +/- 1, 14 +/- 2
      and 20 +/- 3 mg min(-1) vs. control, 51 +/- 2 mg min(-1)). Injection of
      moxonidine (20 nmol in 0.1 ml) i.p. produced no change on i.p. pilocarpine
      induced salivation (58 +/- 4 mg min(-1) vs. control, 50 +/- 4 mg min(-1)). The
      results show that central, but not peripheral, injection of moxonidine inhibits
      pilocarpine-induced salivation, suggesting that central mechanisms activated by
      alpha2-adrenergic/imidazoline agonists inhibit cholinergic-induced salivation in
      rats.

PMID- 11515800
TI  - Urodynamic effects induced by intravesical capsaicin in rats and hamsters.
AB  - This study compared the effect of acute intravesical capsaicin administration on
      transvesical cystometries in urethane-anesthetized rats and hamsters, and aimed
      to assess whether sensory neuropeptides (tachykinins; calcitonin gene-related
      peptide, CGRP) play a role in the urodynamic effects of capsaicin in these
      species. The following urodynamic parameters were evaluated: the mean micturition
      interval (MI), the pressure threshold for micturition (PT), and the mean
      amplitude of micturition contractions (MAC). Two concentrations of capsaicin (10
      and 100 microM) were evaluated in both species. Here, we demonstrate that 10
      microM capsaicin decreased the PT in both rats and hamsters, and 100-microM
      capsaicin decreased the PT in hamsters and decreased the MI in both species. In
      addition, 100-microM capsaicin increased the MAC in rats but decreased the MAC in
      hamsters. Administration of CGRP (10 nmol kg(-1) , i.v.) significantly decreased
      both MAC and PT in hamsters only, while capsaicin-induced desensitization of
      neuropeptide-containing afferents antagonized the urodynamic effects of
      intravesical capsaicin. In addition, administration of the tachykinin NK2
      receptor antagonist, Nepadutant (100 nmol kg(-1), i.v.), reduced the effects of
      capsaicin (100 microM) only in rats. These results indicate that capsaicin
      induces bladder hyperactivity in both rats and hamsters, but the urodynamic
      characteristics of this hyperactivity markedly differ in these two species. The
      differences observed may be due to differential expression of sensory
      neuropeptides in capsaicin-sensitive bladder afferents or neuropeptide receptors
      in smooth muscle cells and in nerve fibers.

PMID- 11515802
TI  - Interrelations of vasoconstrictor sympathetic outflow to skin core temperature
      during unilateral sole heating in humans.
AB  - The purpose of the present study was to clarify how skin sympathetic nerve
      activity (SSNA) influences the core temperature during local heating of the
      unilateral sole of the foot for 60 min. We recorded SSNA microneurographically
      from the tibial or peroneal nerve simultaneously with skin blood flow, sweat rate
      at heated and non-heated sites, with tympanic temperature (Tty) as the core
      temperature. Sole heating began to suppress vasoconstrictive SSNA
      (vasoconstrictor) after 3.4 +/- 1.1 min, decrease Tty after 7.4 +/- 2.0 min,
      activate vasoconstrictor after 33.4 +/- 2.2 min, and increase Tty after 45.5 +/-
      2.7 min. Regarding the interaction between vasoconstrictor and Tty during sole
      heating, we found the following: (1) the capability to suppress vasoconstrictors
      (decrease rate) showed positive correlations with the time delay from
      vasoconstrictor suppression to the Tty decrease (r = 0.752, p < 0.05), and with
      the Tty decrease rate (r = 0.795, p < 0.05), (2) the Tty decrease rate was
      inversely related to the capability to activate vasoconstrictors (increase rate)
      (r= -0.836, p < 0.05), and (3) the capability to activate vasoconstrictors was
      inversely related to the time delay from vasoconstrictor activation to the Tty
      increase (r = -0.856, p < 0.05) and showed a positive correlation with the Tty
      increase rate (r = 0.819, p < 0.05). These significant correlations indicate that
      the capability to control vasoconstrictors to the skin is one of the determinant
      factors maintaining core temperature in human thermoregulatory function. In
      conclusion, human thermoregulatory function is largely dependent on the
      suppression and activation capability of vasoconstrictors.

PMID- 11515801
TI  - Neuromodulation therapy does not influence blood flow distribution or left
      ventricular dynamics during acute myocardial ischemia.
AB  - OBJECTIVES: Electrical stimulation of the dorsal aspect of the upper thoracic
      spinal cord is used increasingly to treat patients with angina pectoris
      refractory to conventional therapeutic strategies. The purpose of this study was
      to determine whether spinal cord stimulation (SCS) in dogs affects regional
      myocardial blood flow and left-ventricular (LV) function before and during
      transient obstruction of the left anterior descending coronary artery (LAD).
      METHODS: In anesthetized dogs, regional myocardial blood flow distribution was
      determined using radiolabeled microspheres and left-ventricular function was
      measured by impedance-derived pressure-volume loops. SCS was accomplished by
      stimulating the dorsal T1-T2 segments of the spinal cord using epidural bipolar
      electrodes at 90% of motor threshold (MT) (50 Hz, 0.2-ms duration). Effects of 5
      min SCS were assessed under basal conditions and during 4-min occlusion of the
      LAD. RESULTS: SCS alone evoked no change in regional myocardial blood flow or
      cardiovascular indices. Transient LAD occlusion significantly diminished blood
      flow within ischemic, but not in non-ischemic myocardial tissue. Left ventricular
      pressure-volume loops were shifted rightward during LAD occlusion. Cardiac
      indices were altered similarly during LAD occlusion and concurrent SCS.
      CONCLUSIONS: SCS does not influence the distribution of blood flow within the non
      ischemic or ischemic myocardium. Nor does it modify LV pressure-volume dynamics
      in the anesthetized experimental preparation.

PMID- 11515803
TI  - A model for the genesis of arterial pressure Mayer waves from heart rate and
      sympathetic activity.
AB  - Both theoretic models and cross-spectral analyses suggest that an oscillating
      sympathetic nervous outflow generates the low-frequency arterial pressure
      fluctuations termed Mayer waves. Fluctuations in heart rate also have been
      suggested to relate closely to Mayer waves, but empiric models have not assessed
      the joint causative influences of heart rate and sympathetic activity. Therefore,
      we constructed a model based simply upon the hemodynamic equation derived from
      Ohm's Law. With this model, we determined time relations and relative
      contributions of heart rate and sympathetic activity to the genesis of arterial
      pressure Mayer waves. We assessed data from eight healthy young volunteers in the
      basal state and in a high sympathetic state known to produce concurrent increases
      in sympathetic nervous outflow and Mayer wave amplitude. We fit the Mayer waves
      (0.05-0.20 Hz) in mean arterial pressure by the weighted sum of leading
      oscillations in heart rate and sympathetic nerve activity. This model of our data
      showed heart rate oscillations leading by 2-3.75 s were responsible for almost
      half of the variance in arterial pressure (basal R2 = 0.435 +/- 0.140, high
      sympathetic R2= 0.438 +/- 0.180). Surprisingly, sympathetic activity (lead 0-5 s)
      contributed only modestly to the explained variance in Mayer waves during either
      sympathetic state (basal: delta R2 = 0.046 +/- 0.026; heightened: delta R2 =
      0.085 +/- 0.036). Thus, it appears that heart rate oscillations contribute to
      Mayer waves in a simple linear fashion, whereas sympathetic fluctuations
      contribute little to Mayer waves in this way. Although these results do not
      exclude an important vascular sympathetic role, they do suggest that additional
      factors, such as sympathetic transduction into vascular resistance, modulate its
      influence.

PMID- 11515804
TI  - Training reduces autonomic cardiovascular responses to both exercise-dependent
      and -independent stimuli in humans.
AB  - Training attenuates the sympathetic pressor response to dynamic exercise.
      However, it is uncertain how training alters other patterns of cardiovascular
      autonomic activation. Therefore, we have quantified circulatory responses to a
      series of standard autonomic tests in highly fit and unfit subjects and examined
      the effects of a short-term training programme on these responses. Subjects were
      defined as either unfit (n = 8) or fit (n = 8) on the basis of training history
      and a maximal fitness test (VO2peak 54 +/- 2.3 cf. 68 +/- 2.8 (ml min(-1)) kg(
      1), means + S.E.M., P < 0.05). On a separate day, the blood pressure, heart rate
      and forearm vascular conductance responses to a sustained handgrip to fatigue, 2
      min mental arithmetic and 2 min of cold exposure were measured. All stimuli were
      associated with elevated blood pressures and heart rates, but these responses
      were significantly attenuated in the trained group. In the untrained subjects,
      forearm vascular conductance increased during exercise (from 0.032 +/- 0.004 to
      0.05 +/- 0.007 (ml min(-1)) 100 ml(-1) mm Hg(-1), P < 0.05) and during mental
      arithmetic (from 0.028 +/- 0.003 to 0.04 +/- 0.006 (ml min(-1)) 100 ml(-1) mm Hg(
      1) , p < 0.05), but trained subjects showed no rise in conductance during either
      test. All untrained subjects undertook a moderate intensity 5-week training
      programme, which significantly increased VO2peak (54 +/- 2.3 to 57 +/- 2 (ml min(
      1)) kg(-1), p < 0.05). Qualitatively similar blunting of pressor, tachycardic and
      vasodilator responses were seen in this group post-training. These results
      demonstrate that the blunting of sympathetic vasomotor activation that follows
      training is not restricted to reflexes associated with exercise, and does not
      depend on training being prolonged or intense.

PMID- 11515805
TI  - Selective impairment of excitatory pressor responses after prolonged simulated
      microgravity in humans.
AB  - The haemodynamic and autonomic effects of prolonged exposure to simulated
      microgravity were assessed non-invasively in seven healthy volunteers completing
      a 42-day -6 degrees head down tilt. Before, during and after head down tilt,
      subjects were exposed to moderate excitatory stimuli (mental arithmetic and
      static handgrip) to gauge possible progressive impairment of pressor responses.
      Before and after head down tilt, subjects were also exposed to orthostatic
      stress, to assess influences of simulated microgravity on orthostatic defence.
      Simple haemodynamics (heart rate and systolic arterial blood pressure), linear
      (i.e., oscillatory) components of beat-by-beat variability, non-linear properties
      (i.e., corrected conditional entropy (CCE)) of RR interval variability, and
      baroreflex slope furnished a non-invasive evaluation of autonomic regulatory
      mechanisms. Pressor responses to mental arithmetic and to handgrip were markedly
      impaired after 42 days head down tilt, whereas responses in markers of autonomic
      regulation were not modified. Standing, performed 8 days after head down tilt to
      limit the risk of syncope, still induced a variable degree of hypotension, with
      signs of progressively greater sympathetic activation than before head down tilt.
      Simulated microgravity-induced reduction of pressor responses, in spite of
      largely maintained autonomic activation, favours the hypothesis of a peripheral
      impairment of cardiovascular homeostasis. rights reserved.

PMID- 11515806
TI  - Innocuous mechanical stimulation of the neck and alterations in heart-rate
      variability in healthy young adults.
AB  - The present study examined the effects of cervical spinal manipulation, a widely
      applied form of physical therapy, which involves innocuous mechanical
      stimulation, on heart rate and heart-rate variability, in a cohort of healthy
      young adults. Using a cross-over treatment design, with a one-week washout period
      and, in contrast to a sham procedure, the authentic manipulation produced
      significant alterations in both heart rate and measures of heart-rate variability
      calculated from power spectrum analysis. In particular, there was an increase in
      the ratio of low-frequency (LF)-to-high-frequency (HF) components of the power
      spectrum of heart-rate variability, which may reflect a shift in balance between
      sympathetic and parasympathetic output to the heart.

PMID- 11515807
TI  - Nitric oxide in immunity and inflammation.
AB  - Nitric oxide (NO) is synthesised by many cell types involved in immunity and
      inflammation. The principal enzyme involved is the inducible type-2 isoform of
      nitric oxide synthase (NOS-2), which produces high-level sustained NO synthesis.
      NO is important as a toxic defense molecule against infectious organisms. It also
      regulates the functional activity, growth and death of many immune and
      inflammatory cell types including macrophages, T lymphocytes, antigen-presenting
      cells, mast cells, neutrophils and natural killer cells. However, the role of NO
      in nonspecific and specific immunity in vivo and in immunologically mediated
      diseases and inflammation is poorly understood. NO does not act through a
      receptor-its target cell specificity depends on its concentration, its chemical
      reactivity, the vicinity of target cells and the way that target cells are
      programmed to respond. At high concentrations as generated by NOS-2, NO is
      rapidly oxidised to reactive nitrogen oxide species (RNOS) that mediate most of
      the immunological effects of NOS-2-derived NO. RNOS can S-nitrosate thiols to
      modify key signalling molecules such as kinases and transcription factors.
      Several key enzymes in mitochondrial respiration are also inhibited by RNOS and
      this leads to a depletion of ATP and cellular energy. A combination of these
      interactions may explain the multiple actions of NO in the regulation of immune
      and inflammatory cells.

PMID- 11515808
TI  - Inducible nitric oxide synthase-derived nitric oxide in gene regulation, cell
      death and cell survival.
AB  - Studies from many laboratories have demonstrated the complex role of NO in
      inflammatory processes. Prolonged exposure to NO shifts the cellular redox
      potential to a more oxidized state and this is critically regulated by
      intracellular levels of reduced glutathione. NO-mediated stress will alter gene
      expression patterns, and the number of genes known to be involved is steadily
      increasing. Indeed, due to its S-nitrosating activity in the presence of oxygen,
      NO can modify the activity of transcription factors containing zinc finger motifs
      or cysteines within the DNA-binding domain. In addition, we are faced with not
      only NO acting as a powerful inducer of apoptosis or of necrosis in some cells,
      but also representing an equally powerful protection from cell death in many
      instances. Some of these apparent discrepancies may be explained by different
      capacities of cells to cope with the stress of NO exposure. Here, we review our
      findings on the complex impact of NO on transcriptional regulation of genes, cell
      death and cell survival. These NO-mediated actions will contribute to a better
      understanding of the impact of inducible nitric oxide synthase (iNOS) enzyme
      activity during inflammatory reactions.

PMID- 11515809
TI  - The regulatory role of nitric oxide in apoptosis.
AB  - Nitric oxide (NO) is a multi-faceted molecule with dichotomous regulatory roles
      in many areas of biology. The complexity of its biological effects is a
      consequence of its numerous potential interactions with other molecules such as
      reactive oxygen species (ROS), metal ions, and proteins. The effects of NO are
      modulated by both direct and indirect interactions that can be dose-dependent and
      cell-type specific. For example, in some cell types NO can promote apoptosis,
      whereas in other cells NO inhibits apoptosis. In hepatocytes, NO can inhibit the
      main mediators of cell death-caspase proteases. Moreover, low physiological
      concentrations of NO can inhibit apoptosis, but higher concentrations of NO may
      be toxic. High NO concentrations lead to the formation of toxic reaction products
      like dinitrogen trioxide or peroxynitrite that induce cell death, if not by
      apoptosis, then by necrosis. Long-term exposure to nitric oxide in certain
      conditions like chronic inflammatory states may predispose cells to tumorigenesis
      through DNA damage, inhibition of DNA repair, alteration in programmed cell
      death, or activation of proliferative signaling pathways. Understanding the
      regulatory mechanisms of NO in apoptosis and carcinogenesis will provide
      important clues to the diagnosis and treatment of tissue damage and cancer. In
      this article we have reviewed recent discoveries in the regulatory role of NO in
      specific cell types, mechanisms of pro-apoptotic and anti-apoptotic induction by
      NO, and insights into the effects of NO on tumor biology.

PMID- 11515810
TI  - NO as a signaling molecule: effects on kinases.

PMID- 11515811
TI  - Nitric oxide in parasitic infections.
AB  - Nitric oxide (NO) is implicated as an integral component of the host armament
      against invading parasites. Strongest evidence has come from laboratory models of
      protozoan infections. During malaria, toxoplasmosis and leishmaniasis, to name
      just a few, the preferential production of pro-inflammatory cytokines predisposes
      to the increased synthesis of NO, which mediates host protection through either
      direct parasite killing or by limiting parasite growth. More recently, evidence
      has been put forward for a beneficial role of NO during helminthic infections. In
      the case of Schistosomiasis mansoni, for example, NO plays a role in regulation
      of egg-induced inflammation, preventing hepatocyte death and widespread tissue
      damage. In spite of these findings, rather than being the ultimate panacea, NO
      production requires tight control to limit cytotoxic damage to the host's own
      cells. Unregulated production may lead to a variety of damaging effects including
      alterations to normal neurological functions during cerebral malaria and
      intestinal pathology during trichinosis. In this review, I will summarize the
      role of NO during a number of parasitic infections, drawing on specific examples
      of disease caused by protozoan and metazoan parasites.

PMID- 11515812
TI  - The role of NO in contact hypersensitivity.
AB  - Contact dermatitis or contact hypersensitivity (CHS) is a common T lymphocyte
      mediated allergic disease characterized by local inflammatory skin reactions
      following contact with small reactive compounds called haptens. In common with
      other allergic processes, the development of contact dermatitis proceeds in two
      phases: a sensitization phase which occurs on first exposure to allergen, and an
      elicitation phase which occurs on subsequent exposure when the clinical
      manifestations of the disease are observed. This process is hapten-specific.
      While the pathophysiology of the sensitization phase is well characterized, our
      understanding of the elicitation phase is still incomplete, including the
      relative contribution of the different effector cells and mediators involved.
      Here we summarize current knowledge of the contribution of nitric oxide (NO) to
      skin inflammation with special focus on CHS. A number of inflammatory stimuli
      trigger expression of NO in human and animal skin, and topical application of an
      NO-releasing cream results in inflammation. Moreover, expression of the inducible
      isoform of nitric oxide synthase (iNOS) is induced in CHS and iNOS inhibitors
      injected intradermally suppress CHS responses. However, iNOS-deficient mice
      develop an aggravated CHS response late in the elicitation phase, suggesting that
      NO is involved in downregulation of CHS. Based on these data, we propose a
      comprehensive model of the role of NO in CHS.

PMID- 11515813
TI  - Human alveolar macrophages and monocytes as a source and target for nitric oxide.
AB  - Nitric oxide (NO) is synthesized in the lung and this free radical participates
      in a wide array of regulatory, protective, and adverse interactions with cells.
      Both excess NO and its insufficiency have been implicated in the pathogenesis of
      numerous lung diseases with inflammatory components. Much of the available data
      concerning the source and regulation of NO production is derived from rodent
      systems. However, the requirements for NO production are more stringent in human
      monocytes/macrophages than in rodent systems. In contrast to rodent macrophages,
      human moncytes/macrophages generally do not respond to cytokine triggers with NO
      production [J. Leukocyte Biol. 58 (1995) 643, J. Exp. Med. 181 (1995) 735] and if
      NO is detected the levels are generally low [J. Leukocyte Biol. 58 (1995) 643].
      The regulation of macrophage NO in the human appears to be a more selective and
      variable process than that seen in the rodent macrophages. In the human lung, the
      function of NO as toxic pro-inflammatory or protective anti-inflammatory agent is
      unresolved. While not a major source of NO in the human lung, the alveolar
      macrophage is an important producer of cytokines and this production may be
      modified by NO. Clear evidence of abnormalities in NO levels in the lungs of
      patients with asthma, bronchiectasis, viral infections, lung cancer and primary
      pulmonary hypertension (PPH) has been documented. Elevated inflammatory cytokines
      and oxidant production have been associated with all of these disease states. In
      terms of cytokine production, NO has been shown to decrease nuclear factor kappa
      B (NF-kappaB) activation. However, oxidants may interact with NO to form toxic
      compounds (e.g., NO combines with superoxide anion to form peroxynitrite).
      Furthermore, such reactions may decrease the availability of NO for blocking
      inflammatory cytokine production. Thus, available data suggests that a
      multiplicity of factors affect NO regulatory properties in inflammatory
      situations.

PMID- 11515814
TI  - Nitric oxide and T helper cell immunity.
AB  - In this article, the controversial role of nitric oxide (NO) in T helper (Th)
      cell activation and T-cell-dependent immunity will be discussed with an emphasis
      on immunosuppression by NO. NO is generated by antigen-presenting cells (APC)
      during the process of antigen presentation to T cells. In mouse models,
      activation of the inducible NO synthase (iNOS) in APC is triggered by Th1-cell
      derived IFN-gamma, in combination with other soluble or membrane-associated T
      cell factors. The NO so-produced inhibits T-cell proliferation, while it does not
      inhibit T cell cytokine production. NO blocks T-cell proliferation during G1/S
      transition. In mouse models of T-cell-mediated autoimmunity such as myelin
      antigen-induced EAE, the disease is exacerbated by genetic deletion of iNOS,
      indicating that NO suppresses T-cell-mediated immunity in vivo. Recent studies
      reveal that interaction with superoxide diminishes the T-cell regulatory activity
      of NO. The role for NADPH oxidase as a source for NO-inhibiting superoxide is
      discussed. In conclusion, NO plays an important regulatory role in the induction
      phase of T-cell-mediated immunity. Superoxide may enhance T-cell-mediated
      immunity by preventing the immunosuppressive activity of NO.

PMID- 11515816
TI  - Natural killer cells and nitric oxide.
AB  - Natural killer (NK) cells and nitric oxide (NO) are both important components of
      the natural or innate immune response. NK cells are large granular lymphocytes
      capable of destroying cells infected by virus or bacteria and susceptible tumor
      cells without prior sensitization and restriction by MHC antigens. They are
      abundant in blood, spleen, liver and lungs and are distinct from both T and B
      lymphocytes in their circulation patterns, profile of surface antigens, receptor
      repertoire and the way in which they discriminate between self and non-self.
      Uniquely, NK cells express receptors that can recognize and discriminate between
      normal and altered MHC class I determinants. NK cell cytotoxic activity is
      strongly induced by cytokines such as IL-2 and IL-12, and this activation is
      associated with synthesis of NO. Inhibitors of NO synthesis impair NK cell
      mediated target cell killing, demonstrating a role for NO in NK cell function.
      Furthermore, NO itself can regulate NK cell activation. In this article, evidence
      that NO is a mediator of NK cell-mediated target cell killing, and that NO is a
      regulator of NK cell activation will be reviewed. Results of NO synthase gene
      deletion studies will be discussed, and rodent and human NK cells will be
      compared.

PMID- 11515815
TI  - The physiological role and pharmacological potential of nitric oxide in
      neutrophil activation.
AB  - There is contention over whether human neutrophils produce physiologically
      significant levels of nitric oxide (NO) during inflammatory reactions.
      Nevertheless, regardless of its cell source, NO does exert regulatory effects on
      neutrophil function. Depending on experimental conditions, NO can either inhibit
      or enhance neutrophil activation, in both cases probably acting through cyclic
      GMP. The explanation for these apparently contradictory findings may be that the
      effect depends upon the concentration of NO: low concentrations of NO being
      stimulatory and high concentrations inhibitory. Nitrite, produced at high
      concentrations from NO during inflammation, can react with neutrophil
      myeloperoxidase-derived hypochlorous acid (HOCl) to form the active oxidant
      nitryl chloride, a species capable of nitrating tyrosine and tyrosyl residues on
      proteins. Whether nitryl chloride acts to limit or amplify the oxidant effects of
      myeloperoxidase is not yet clear, although formation of nitrotyrosine has been
      linked with nitration of phagocytosed bacteria. Clearly, a better understanding
      of the inflammatory effects of NO on neutrophils is needed before the therapeutic
      potential of NO donors or inhibitors in inflammation can be realised.

PMID- 11515817
TI  - Mast cells and nitric oxide: control of production, mechanisms of response.
AB  - Mast cells are involved in numerous activities ranging from control of the
      vasculature, to tissue injury and repair, allergic inflammation and host
      defences. They synthesize and secrete a variety of mediators, activating and
      modulating the functions of nearby cells and initiating complex physiological
      changes. Interestingly, NO produced by mast cells and/or other cells in the
      microenvironment appears to regulate these diverse roles. This review outlines
      some of the pathways central to the production of NO by mast cells and identifies
      many of the tightly controlled regulatory mechanisms involved. Several cofactors
      and regulatory elements are involved in NO production, and these act at
      transcriptional and post-translational sites. Their involvement in NO production
      will be outlined and the possibility that these pathways are critically important
      in mast cell functions will be discussed. The effects of NO on mast cell
      functions such as adhesion, activation and mediator secretion will be examined
      with a focus on molecular mechanisms by which NO modifies intracellular
      signalling pathways dependent or independent of cGMP and soluble guanylate
      cyclase. The possibility that NO regulates mast cell function through effects on
      selected ion channels will be discussed. Metabolic products of NO including
      peroxynitrite and other reactive species may be the critical elements that affect
      the actions of NO on mast cell functions. Further understanding of the actions of
      NO on mast cell activities may uncover novel strategies to modulate inflammatory
      conditions.

PMID- 11515818
TI  - Mast cells as a source and target for nitric oxide.
AB  - Mast cells (MC), which are tissue-resident cells found widely distributed in the
      body, are derived from primitive hematopoietic cells. MC produce a variety of
      biologically active substances such as histamine, proteases, lipid derivatives
      and numerous cytokines and chemokines in response to immunologic or non
      immunologic stimuli. Of interest, it has been reported that rodent MC can also be
      a source of nitric oxide (NO) derivatives, that they synthesize spontaneously, or
      only after activation, depending on their subtype. This synthesis appears to be
      under the control of the expression of the inducible isoform of the nitric oxide
      synthase (iNOS) and of the constitutive neuronal NOS (nNOS). MC might thus be
      able to influence the survival and functions of other types of NO-sensitive cells
      in close vicinity. Apart from being a source of NO, MC can also be the target for
      NO and its derivatives. Indeed, survival and reactivity of rodent MC is
      influenced by NO derivatives produced by MC themselves or by other cellular
      elements in close contact with the MC in tissues. By contrast, the existence of
      such mechanisms of cross-talk between MC and NO remains poorly documented in
      humans. If evidence are supplied in favor of such relationship, pharmacological
      modulation by agents acting at the level of the NO pathway might be of interest
      in order to regulate the functions of MC in immunologic, neoplastic, inflammatory
      and other conditions.

PMID- 11515820
TI  - Acute morphine treatment alters cellular immune function in the lungs of healthy
      rats.
AB  - Previous work has shown that morphine suppresses the pulmonary immune response to
      infection and reduces pulmonary inflammation. No published studies have addressed
      the impact of morphine on lymphocyte function in the lungs without infection.
      This study addressed this question by assessing the impact of acute morphine
      treatment on proliferation, cytokine production, and natural killer (NK) cell
      activity in resident pulmonary lymphocytes from healthy rats. Male Lewis rats
      received either a single 15 mg/kg morphine sulfate or vehicle injection 1 h prior
      to sacrifice. Lungs were minced and passed through wire mesh following
      collagenase digestion. The resulting cell preparations were pooled (2 rats/pool)
      to yield sufficient cell numbers for the functional assays, and a portion of
      these suspensions were separated using a density gradient. Crude and purified
      cell suspensions were used in assays of NK cell activity and mitogen-induced
      proliferation and cytokine production. Morphine significantly suppressed
      lymphocyte proliferation and cytokine production in whole cell suspensions, but
      not in purified cultures. NK activity was enhanced by morphine treatment in
      purified treated cultures. Studies of nitrate/nitrite levels in crude and
      purified cultures suggest that macrophage-derived nitric oxide may be a mechanism
      of the suppression observed in whole cell suspensions following morphine
      treatment. These data are consistent with previous work showing that morphine
      suppresses mitogenic responsiveness and NK activity in the spleen and peripheral
      blood, and may do so through a macrophage-derived nitric oxide mechanism.

PMID- 11515819
TI  - Interferon gamma-producing ability in blood lymphocytes of patients with lung
      cancer through activation of the innate immune system by BCG cell wall skeleton.
AB  - An in vitro assay system was developed to assess the potency of the human innate
      immune system by measurement of IL-12, IL-18, IL-10 and IFNgamma in the
      supernatants of bacillus Calmette-Guerin cell wall skeleton (BCG-CWS)-stimulated
      blood samples. BCG-CWS is a ligand for Toll-like receptor (TLR) 2 and 4, and
      activates monocytes to macrophages (Mphi), and immature dendritic cells to mature
      antigen-presenting cells (APC). This system was found to allow the discrimination
      of immune suppressive states in patients with lung cancer from normal immune
      states in light of the cytokine profile. The following results were deduced from
      analyses of BCG-CWS-stimulated blood samples of lung cancer patients with
      reference to normal subjects. (1) The levels of production of IFNgamma and IL-10
      by lymphocytes were decreased. (2) IL-12 p40 production by monocytes/Mphi was
      upregulated, while that of IL-10 was downregulated. (3) IL-18 was detected in all
      patients in a range similar to normal subjects. (4) Responses of lymphocytes to
      IL-2 and IL- 18 in terms of IFNgamma production were diminished. (5) The
      upregulated IL-12 levels were recovered to within the normal range in most
      patients after tumor resection. (6) Male patients showed more severe suppression
      of IL-12/IL-18-mediated IFNgamma production than female patients. Thus, the
      lesser IFNgamma production observed in patients' blood with high IL-12 p40 levels
      in response to BCG-CWS may reflect the production of p40 dimers or IL-23 instead
      of p70, or the presence of some unknown pathways to prohibit the interface
      between the innate and acquired immune systems. BCG-CWS-mediated Toll signaling
      may participate in IFNgamma induction for lymphocytes through Mphi/APC IL-12/I-18
      modulation.

PMID- 11515821
TI  - The potentiation of human C1-inhibitor by dextran sulphate is transient in vivo:
      studies in a rat model.
AB  - C1-inhibitor (C1-Inh) is an important regulator of inflammatory reactions because
      it is a potent inhibitor of the contact and complement system. C1-Inh application
      in inflammatory disease is, however, restricted because of the high doses
      required. The glycosaminoglycan-like molecule dextran sulphate (DXS) enhances C1
      Inh function in vitro. Hence, we investigated whether co-administration with
      dextran sulphate reduces the amount of C1-Inh required, through enhancement in
      vivo. C1-Inh potentiation was measured in a newly developed C1s-inactivation
      assay that is based on activation of C4 by purified C1s. Activated C4 in rat
      plasma was quantified with a newly developed ELISA. Human C1-Inh (2.5 microM)
      inhibited C1s in rat plasma 55-fold faster in the presence of dextran sulphate
      (15 kDa, 5 microM). To study the stability of the complex in vivo, rats were
      given a mixture of C1-Inh (10 mg/kg) and dextran sulphate (3 mg/kg). C1-Inh
      activity during 5 h was analyzed ex vivo with the C1s inactivation assay. The
      noncovalent C1-Inh-dextran sulphate complex resulted in a transient enhancement
      of the inhibitory capacity of C1-Inh, lasting for 60-90 min. Dextran sulphate did
      not affect plasma clearance of C1-Inh. We conclude that the enhanced inhibitory
      capacity of C1-Inh complexed to dextran sulphate is transient in vivo. Hence, co
      administration of these compounds seems a feasible approach to achieve short-term
      inhibition of complement in vivo.

PMID- 11515822
TI  - Changes in serum levels of cytokines in mice injected with an immunostimulator
      C3bgp isolated from Cuscuta europea.
AB  - The effect of C3 binding glycoprotein (C3bgp), isolated from Cuscuta europea
      seeds on induction of in vivo cytokine synthesis was investigated. Different
      groups of mice were stimulated with 30 microg C3bgp per mouse, injected
      intraperitoneally. The quantitative determination of IL-1alpha, IL-2, IL-4, IL-6,
      IL-10, TNF-alpha and IFN-gamma was performed in mouse sera by ELISA. The
      quantities of these cytokines were measured at different hours: 1, 2, 3, 4, 5, 6,
      7, and 24 h after injection. No significant changes in serum level of IL-2, IL-4
      and TNF-alpha in experimental animal groups were found. A little increase of IL
      1alpha, moderate elevation of IL-10 and IFN-gamma (5- to 6-fold more) and strong
      release, more than 10-fold of IL-6 in sera of C3bgp-treated mice were detected.
      The results obtained from C3bgp stimulated cultures of mouse peritoneal
      macrophages and mouse splenocytes suggest that C3bgp binds to mouse peritoneal
      macrophages and induces production mainly of IL-6, followed by IFN-gamma and in a
      very low degree of IL-1alpha and IL-10. Based on the results presented, we
      conclude that the increased level of IL-6 was the basic after injection of C3bgp
      and that the mouse macrophages were the major cell targets for the C3bgp effect.

PMID- 11515823
TI  - Bacterial DNA does not increase serum corticosterone concentration or prevent
      increases induced by other stimuli.
AB  - Bacterial DNA containing unmethylated CpG motifs (CpG DNA) and other microbial
      molecules such as lipopolysaccharide (LPS) have a broad range of immune
      stimulatory effects, which may include many shared cell signaling pathways
      leading to enhanced cytokine production. Some cytokines activate the hypothalamic
      pituitary-adrenal (HPA) axis, and their production is downregulated by products
      of the HPA axis (glucocorticoids). Because such interactions have practical
      implications in the clinical use of CpG DNA, the present study was done to
      examine the effects of CpG DNA and LPS on serum corticosterone concentrations. In
      contrast to LPS, administration of CpG DNA (DNA from Escherichia coli) (30-300
      microg) alone did not significantly increase serum corticosterone concentrations
      1 or 4 h after administration. Administration of CpG DNA to mice prior to LPS
      caused a synergistic increase in serum tumor necrosis factor-alpha (TNF-alpha),
      indicative of an immune stimulatory effect. LPS and TNF-alpha, however, induced
      similar levels of corticosterone with or without concomitant CpG DNA. Increasing
      doses of LPS caused peak corticosterone levels similar to those induced by LPS in
      combination with CpG DNA. Exogenous TNF-alpha administered in vivo induced
      comparable concentrations of corticosterone with or without CpG DNA. An
      alternative stressor (restraint) yielded similar levels of corticosterone with or
      without CpG DNA. These results indicate that CpG DNA does not induce
      corticosterone release or alter its release by other stimuli, indicating
      biologically important differences in its immune effect compared to those of LPS,
      and possibly reduced toxicity.

PMID- 11515824
TI  - Melatonin antagonises the cyclosporine A immunosuppressive effects in rat
      thymuses.
AB  - Cyclosporine A (CsA) is a powerful immunosuppressant inducing marked involution
      of the thymus with disappearance of interdigitating cells (IDCs) and reducing the
      number of macrophages (Mphi). Melatonin (Mel) is a potent antioxidant agent that
      could be useful in attempting to reduce CsA toxicity. Moreover, Mel has been
      found to exert positive influence on lymphocytes, spleen and thymus. In this
      study, we evaluated the effects of Mel on the thymic involution induced by CsA.
      CsA caused profound changes in thymic cytoarchitecture, i.e. the complete
      disappearance of thymic medulla and reduced the number of acid phosphatase
      positive macrophages. There was no difference between thymic morphology of Mel
      treated rats and the control animals injected only with olive oil. The
      simultaneous Mel-CsA administration prevented the involution of the thymic
      medulla and the reduction of the number of macrophages. These findings suggested
      that Mel probably antagonized the immunosuppressive CsA effects.

PMID- 11515825
TI  - Americans view AIDS as one of the top health concerns facing the nation.

PMID- 11515826
TI  - Challenges in eating disorders: past and present.

PMID- 11515827
TI  - Comments on spiritual assessment and medicine.

PMID- 11515828
TI  - Comments on spiritual assessment and medicine.

PMID- 11515829
TI  - Comments on spiritual assessment and medicine.

PMID- 11515830
TI  - Comments on spiritual assessment and medicine.

PMID- 11515831
TI  - Evaluating the child with purpura.
AB  - Purpura is the result of hemorrhage into the skin or mucosal membrane. It may
      represent a relatively benign condition or herald the presence of a serious
      underlying disorder. Purpura may be secondary to thrombocytopenia, platelet
      dysfunction, coagulation factor deficiency or vascular defect. Investigation to
      confirm a diagnosis or to seek reassurance is important. Frequently, the
      diagnosis can be established on the basis of a careful history and physical
      examination, and a few key laboratory tests. Indicated tests include a complete
      blood cell count with platelet count, a peripheral blood smear, and prothrombin
      and activated partial thromboplastin times.

PMID- 11515832
TI  - The abdominal wall: an overlooked source of pain.
AB  - When abdominal pain is chronic and unremitting, with minimal or no relationship
      to eating or bowel function but often a relationship to posture (i.e., lying,
      sitting, standing), the abdominal wall should be suspected as the source of pain.
      Frequently, a localized, tender trigger point can be identified, although the
      pain may radiate over a diffuse area of the abdomen. If tenderness is unchanged
      or increased when abdominal muscles are tensed (positive Carnett's sign), the
      abdominal wall is the likely origin of pain. Most commonly, abdominal wall pain
      is related to cutaneous nerve root irritation or myofascial irritation. The pain
      can also result from structural conditions, such as localized endometriosis or
      rectus sheath hematoma, or from incisional or other abdominal wall hernias. If
      hernia or structural disease is excluded, injection of a local anesthetic with or
      without a corticosteroid into the pain trigger point can be diagnostic and
      therapeutic.

PMID- 11515833
TI  - Impact of anorexia, bulimia and obesity on the gynecologic health of adolescents.
AB  - Dieting behaviors and nutrition can have an enormous impact on the gynecologic
      health of adolescents. Teenaged patients with anorexia nervosa can have
      hypothalamic suppression and amenorrhea. In addition, these adolescents are at
      high risk of osteoporosis and fractures. Unfortunately, data suggest that
      estrogen replacement, even in combination with nutritional supplementation, does
      not appear to correct the loss of bone density in these patients. Approximately
      one half of adolescents with bulimia nervosa also have hypothalamic dysfunction
      and oligomenorrhea or irregular menses. Generally, these abnormalities do not
      impact bone density and can be regulated with interval dosing of progesterone or
      regular use of oral contraceptives. In contrast, the obese adolescent with
      menstrual irregularity frequently has anovulation and hyperandrogenism, commonly
      referred to as polycystic ovary syndrome. Insulin resistance is thought to play a
      role in the pathophysiology of this condition. While current management usually
      involves oral contraceptives, future treatment may include insulin-lowering
      medications, such as metformin, to improve symptoms. Because all of these
      patients are potentially sexually active, discussion about contraception is
      important.

PMID- 11515834
TI  - The V-Y plasty in the treatment of fingertip amputations.
AB  - Fingertip amputations are injuries commonly seen by family physicians. The
      classification of fingertip injuries corresponds with the normal anatomy of the
      tip of the digit. There are three zones of injury; the V-Y plasty technique is
      used to repair zone II injuries. The plane of the injury can be described as
      dorsal, transverse or volar. The dorsal and transverse planes lend themselves to
      the use of the V-Y plasty technique. In carefully selected injuries, the family
      physician can use this technique to repair the injured digit. The use of a single
      V-Y plasty has replaced the original technique that repaired the digit and
      restored the contour of the fingertip. Good cosmetic and functional results can
      be obtained. Complications may include flap sloughing, infection and sensory
      changes.

PMID- 11515835
TI  - Tick-borne diseases.
AB  - Tick-borne diseases are the most common vector-borne illnesses in the United
      States. Lyme disease is the most common, but several others also occur. The
      ehrlichioses have only been identified as agents of human disease in the United
      States in the past few decades, and knowledge about them is still evolving. Rocky
      Mountain spotted fever is relatively common and can be severe, especially in
      children, if the diagnosis is not made quickly. Tularemia has long been known to
      cause disease in humans, but there is renewed interest because of its potential
      as a biologic warfare agent. These diseases can be severe or even fatal. Most of
      them are easily treatable when identified early. These diseases result from a
      variety of infectious agents including bacteria, rickettsia, viruses and
      protozoa, or they may be caused by substances produced by the tick. Most of these
      diseases present initially with nonspecific symptoms and are often difficult to
      recognize. Few definitive diagnostic tests are available. Therefore, knowledge of
      the epidemiology and common presentations, as well as the diagnostic options and
      treatments available, are important issues for family physicians.

PMID- 11515836
TI  - Information from your family doctor. What you should know about tick-borne
      diseases.

PMID- 11515837
TI  - Should we prescribe antibiotics for acute otitis media?

PMID- 11515838
TI  - Photo quiz. Pitted palms and fingers.

PMID- 11515839
TI  - Principles of appropriate antibiotic use: Part II. Nonspecific upper respiratory
      tract infections.

PMID- 11515840
TI  - American Heart Association scientific statement on the primary prevention of
      ischemic stroke.

PMID- 11515841
TI  - A case of physician burnout.

PMID- 11515842
TI  - An open-label pilot study using thioguanine as a therapeutic alternative in
      Crohn's disease patients resistant to 6-mercaptopurine therapy.
AB  - BACKGROUND AND AIMS: A substantial number of patients with inflammatory bowel
      disease (IBD) fail to achieve a complete clinical response with 6-mercaptopurine
      (6-MP) and azathioprine (AZA). Inability to achieve therapeutic 6-thioguanine
      nucleotide (6-TGN) levels due to the preferential overproduction of 6
      methylmercaptopurine ribonucleotides (6-MMPR) upon dose escalation characterizes
      a newly described subgroup of IBD patients resistant to 6-MP/AZA therapy.
      Treatment with 6-thioguanine (6-TG), a related thiopurine, which forms 6-TGNs
      more directly may be beneficial in such patients. This pilot study evaluated the
      safety, tolerance, and efficacy of 6-TG in the subgroup of Crohn's disease (CD)
      patients failing to attain adequate disease control with traditional 6-MP/AZA
      therapy. METHODS: Ten CD patients with preferential 6-MMPR production upon 6
      MP/AZA dose escalation were enrolled in an open-label pilot study. Seven of 10
      patients had experienced dose-related 6-MP toxicities. RESULTS: Seventy percent
      of the patients (7 of 10) responded or were in remission at week 16. Clinical
      response was evident by week 4 in most. 6-TGN levels were nine-fold higher with 6
      TG treatment than with 6-MP, whereas 6-MMPR levels were undetectable. No patient
      developed a recurrence of hepatic or hematological toxicity. CONCLUSIONS: 6-TG
      was a safer and more efficacious thiopurine in this subgroup of IBD patients
      resistant to 6-MP therapy. Larger controlled trials are warranted to further
      evaluate both the short- and long-term safety and efficacy in this subgroup of
      patients as well as a broader spectrum of IBD patients.

PMID- 11515843
TI  - 6-Thioguanine: a naked bullet? (Or how pharmacogenomics can make old drugs brand
      new).

PMID- 11515845
TI  - Glucocorticoid receptor mRNA in patients with ulcerative colitis: a study of
      responders and nonresponders to glucocorticosteroid therapy.
AB  - BACKGROUND AND AIMS: Up to 30% of patients with severe-to-moderate attacks of
      ulcerative colitis (UC) respond poorly to glucocorticosteroid (GCS) treatment.
      The reason for this unresponsiveness is unknown. AIM: Our aim was to evaluate
      possible differences in glucocorticoid receptor (GR) density in peripheral
      leukocytes and effects of low-dose GCS treatment on GR density and on the
      hypothalamic-pituitary-adrenal axis in UC patients who had received high-dose GCS
      treatment due to a moderate or severe attack. Eleven UC patients in remission who
      were responders (Rs) to previous GCS treatment were compared with 10 patients who
      failed GCS therapy and had a colectomy (nonresponders. NRs). Ten healthy
      individuals served as controls. METHODS: Quantitation of GR mRNA by a solution
      hybridization assay in peripheral leukocytes and a low-dose adrenocorticotropin
      hormone stimulation test was performed before and after low-dose dexamethasone
      (DEX) treatment for 14 days. The glucocorticoid-responsive gene for
      metallothionein IIa (MTIIa) was also analyzed by a solution hybridization assay
      in peripheral leukocytes. RESULTS: Overall, basal GR mRNA levels were higher in
      patients than in controls (p < 0.0001). There were no significant differences
      between NRs and Rs. None of the groups down-regulated their GR mRNA levels in
      response to DEX treatment. Basal and stimulated cortisol levels decreased
      significantly only among NRs after DEX (p = 0.012 and 0.0093). MTIIa levels were
      lower in NRs as compared with Rs, both in mononuclear (p = 0.0059) and in
      polynuclear leukocytes (p = 0.030). CONCLUSION: Patients with UC in remission
      exhibit higher levels of GR mRNA in peripheral leukocytes. We speculate that this
      may be secondary to an underlying up-regulation of proinflammatory factors also
      present in patients in clinical remission. Differences in GR mRNA levels per se
      thus may not be important for the ability of patients with UC to respond to GCS
      treatment. The hypothalamic pituitary adrenal axis was suppressed by low-dose DEX
      treatment only in NRs, possibly indicating that steroid-resistance is not a
      generalized phenomenon. Lower levels of MTIIa in NRs may indicate a diminished
      efficiency of GR regulation in steroid-refractory patients.

PMID- 11515844
TI  - Evaluation of serologic disease markers in a population-based cohort of patients
      with ulcerative colitis and Crohn's disease.
AB  - BACKGROUND: The sensitivity of assays for antineutrophil cytoplasmic antibody
      (ANCA), anti-Saccharomyces cerevisiae antibody (ASCA), and antipancreatic
      antibody (PAB) in different laboratories is unknown. Likewise, the sensitivity
      and diagnostic usefulness of these assays in patients with inflammatory bowel
      disease (IBD) in the community is unknown. METHODS: An incidence cohort of 290
      patients with IBD were offered participation in the study. Blood was obtained
      from 162 patients (56%) (83 with ulcerative colitis, 79 with Crohn's disease) who
      agreed to participate. ANCA was determined in five laboratories. ASCA in two
      laboratories, and PAB in one laboratory. RESULTS: In ulcerative colitis, the
      sensitivity of ANCA determined in five laboratories varied widely, ranging from 0
      63%. In Crohn's disease, the sensitivity of ASCA determined in two laboratories
      did not vary significantly, ranging from 39-44%; and the sensitivity of PAB
      determined in one laboratory was 15%. The optimal diagnostic usefulness was
      obtained from one laboratory where the positive predictive values of a positive
      ANCA assay combined with a negative ASCA assay for ulcerative colitis, and a
      negative ANCA combined with a positive ASCA for Crohn's disease, were 75% and
      86%, respectively. CONCLUSIONS: In patients with IBD, the sensitivity of ANCA
      varied widely in different laboratories, whereas the prevalence of ASCA was
      similar. The positive predictive values of the ANCA assay combined with the ASCA
      assay for ulcerative colitis and Crohn's disease are high enough to be clinically
      useful.

PMID- 11515846
TI  - Epithelial expression of caveolin-2, but not caveolin-1, is enhanced in the
      inflamed mucosa of patients with ulcerative colitis.
AB  - Caveolae are vesicular invaginations of the plasma membrane that act as a
      scaffold of the assembly of many classes of signaling molecules. Caveolins are
      the principal structural component of caveolae membranes, and three distinct
      forms of caveolins have been identified: caveolin-1, caveolin-2, and caveolin-3.
      In this study, we evaluated the changes in the caveolin-1 and caveolin-2
      expression in the inflamed mucosa of patients with IBD. Tissue samples were
      obtained endoscopically from patients with ulcerative colitis (UC) (n = 18),
      Crohn's disease (n = 10) and ischemic colitis (n = 8). Normal colorectal tissues
      were also obtained (n = 15). The caveolin expression was evaluated by standard
      immunohistochemical procedure. In normal colonic mucosa, caveolin-1 expression
      was detected in the smooth-muscle cells of the muscularis mucosae and the
      endothelial cells, but caveolin-2 expression was not detected. In the inflamed
      mucosa of patients with active UC, caveolin-2 expression was clearly detectable
      as small scattered foci on the luminal surfaces of epithelial cells, but caveolin
      1 expression was similar to that in normal mucosa. Caveolin-2 expression
      increased in accordance with the disease activity of UC. This enhanced caveolin-2
      expression was not detected in active Crohn's disease or ischemic colitis. In
      conclusion, we demonstrated that the epithelial expression of caveolin-2 is
      markedly enhanced in the inflamed mucosa of patients with UC. It is likely that
      the enhanced caveolin-2 expression in patients with UC was associated with the
      altered signal transductions in the intestinal epithelial cells. Furthermore, our
      results suggest that there are differences in the phenotypic features of
      epithelial cells between UC and Crohn's disease.

PMID- 11515847
TI  - The expression of IL-12 p40 and its homologue, Epstein-Barr virus-induced gene 3,
      in inflammatory bowel disease.
AB  - BACKGROUND: It has recently been suggested that Crohn's Disease (CD) is
      associated with an exaggerated T helper 1 cytokine response as manifest by
      increased production of interleukin-12 (IL-12) and interferon-gamma (IFN-gamma).
      Epstein-Barr virus-induced gene 3 (EBI3) encodes a 34-kDa glycoprotein that is
      27% identical to the p40 unit of IL-12 and has recently been reported to be up
      regulated in ulcerative colitis (UC). AIM: To determine whether mucosal
      expression of IL-12 p40 or EBI3 correlates with inflammatory bowel disease (IBD).
      PATIENTS/METHODS: mRNA expression in colonic mucosa from patients with UC,
      Crohn's disease (CD) and non-IBD controls was measured by reverse-transcribed
      real-time polymerase chain reaction (PCR). RESULTS: EBI3 was significantly
      increased in both involved and uninvolved colonic mucosa in patients with UC.
      Although IL-12 p40 was increased in some patients with CD relative to non-IBD
      controls, the increase was not statistically significant. However, 5
      aminosalicylic acid (5-ASA) use was significantly correlated with reduced IL-12
      p40 levels in the patients with CD, but not in UC cases. A similar reduction was
      not seen in 5-ASA-treated UC patients. CONCLUSION: IL-12 p40 expression in CD is
      heterogeneous. In contrast, expression of the IL-12 p40 homologue, EBI3, is up
      regulated in nearly all UC cases and in a subset of CD.

PMID- 11515848
TI  - Measurement of colonic mucosal concentrations of 5-aminosalicylic acid is useful
      for estimating its therapeutic efficacy in distal ulcerative colitis: comparison
      of orally administered mesalamine and sulfasalazine.
AB  - OBJECTIVES: Oral 5-aminosalicylic acid (5-ASA) preparations have been used
      frequently in the treatment of ulcerative colitis. However, there have been few
      reports investigating the relationship between colonic mucosal concentrations of
      5-ASA and its clinical efficacy when oral sulfasalazine or 5-ASA compounds were
      administered. The aim of this study is to compare the mucosal concentrations of 5
      ASA ensured by sulfasalazine or mesalamine, and to define the clinical
      significance of the measurement of 5-ASA concentrations in the treatment of
      distal ulcerative colitis. MATERIALS AND METHODS: Biopsies were taken from the
      rectum and sigmoid colon of the oral sulfasalazine group (n = 13) and the slow
      release 5-ASA (mesalamine) group with (n = 5) or without (n = 11) rectal
      administration of 5-ASA. High-pressure liquid chromatography was used to measure
      the tissue concentrations of 5-ASA and its metabolites. We compared the 5-ASA
      concentrations of the sulfasalazine group with the mesalamine group. Furthermore,
      we analyzed the relationship between tissue 5-ASA concentrations and the Disease
      Activity Index (DAI). RESULTS: The concentrations of 5-ASA and acetyl-5-ASA in
      the sulfasalazine group were higher than those in the group taking oral
      mesalamine alone (p < 0.01). The concentration of 5-ASA was much higher in the
      patients who received oral and rectal mesalamine in an enema than in the patients
      who had oral mesalamine alone. There was a significant inverse correlation
      between the DAI and concentrations of 5-ASA in the rectum (r = 0.712, p < 0.001).
      CONCLUSIONS: We demonstrated that the colonic mucosal concentration of 5-ASA was
      significantly higher in the sulfasalazine group than in the mesalamine group.
      Furthermore, the concentrations of mucosal 5-ASA may be a good marker for the
      estimation of its efficacy in the treatment of ulcerative colitis.

PMID- 11515849
TI  - Altered response of intestinal mucosal fibroblasts to profibrogenic cytokines in
      inflammatory bowel disease.
AB  - BACKGROUND AND AIMS: Fibrosis is a major complication of inflammatory bowel
      disease (IBD), which may be mediated by the intestinal fibroblast. Our aim was to
      isolate and characterize mucosal fibroblasts from histologically normal intestine
      (control), ulcerative colitis (UC), inflamed Crohn's disease (CD), and fibrosed
      CD intestine. METHODS: Fibroblasts were characterized by light and electron
      microscopy and immunohistochemistry. Fibroblast collagen secretion and
      proliferation were determined by 3H-proline and 3H-thymidine incorporation, and
      the effects of exposure to interleukin (IL)-1beta, basic fibroblast growth factor
      (bFGF), platelet-derived growth factor (PDGF), transforming growth factor (TGF)
      beta1, insulin-like growth factor (IGF)-1, and macrophage colony stimulating
      factor (M-CSF) were determined. RESULTS: No difference in doubling time was
      observed between the fibroblast populations from UC and CD intestine. All
      proliferated faster than fibroblasts from control intestine. Collagen secretion
      from IBD fibroblasts, independent of type, was increased compared with control
      fibroblasts and PDGF, bFGF, and TGF-beta1-induced collagen secretion from IBD
      fibroblasts. CONCLUSIONS: These results suggest the presence of an activated
      subpopulation of fibroblasts in both UC and CD tissue irrespective of the
      presence of tissue fibrosis or disease type.

PMID- 11515850
TI  - Mesalazine 4 g daily given as prolonged-release granules twice daily and four
      times daily is at least as effective as prolonged-release tablets four times
      daily in patients with ulcerative colitis.
AB  - BACKGROUND: High doses of mesalazine usually result in an inconvenient dosage
      schedule and reduced compliance. The goal of this trial was to compare the
      effects of mesalazine 4 g daily given as prolonged-release granules in packets of
      1 g with that of prolonged-release tablets of 0.5 g. METHODS: Two hundred twenty
      seven patients with mild-to-moderate ulcerative colitis were randomized to
      treatment with two packets twice daily (Gr-b.i.d.), 1 packet four times daily (Gr
      q.i.d.) or 2 tablets four times daily (Ta-q.i.d.) for 8 weeks. A disease activity
      index (ulcerative colitis disease activity index: UC-DAI) was calculated, and the
      granules were defined as noninferior to the tablets if the lower limit of the 95%
      CI for the differences was more than -1 UC-DAI score unit. RESULTS:
      Noninferiority of the granules compared with the tablets was demonstrated. The
      mean improvement in the UC-DAI in the treatment groups Gr-b.i.d., Gr-q.i.d., and
      Ta-q.i.d. were 3.2, 2.9, and 2.4, respectively; the proportion of complete
      responders in the three groups 39%, 37%, and 31%, respectively. There were no
      differences in side effects. CONCLUSION: Mesalazine 4 g daily given as prolonged
      release granules twice and four times daily is at least as effective as prolonged
      release tablets four times daily in patients with mild to moderate ulcerative
      colitis. The patients preferred the twice daily dosing.

PMID- 11515851
TI  - Colonoscopic findings in intestinal Behcet's disease.
AB  - The aims of this study were to investigate the clinical and colonoscopic
      characteristics of patients with intestinal Behcet's disease and to compare the
      findings of typical and atypical intestinal Behcet's disease. Ninety-four
      patients diagnosed as having intestinal Behcet's disease were included. Of these,
      we considered 42 patients as having complete or incomplete type; these fulfilled
      the international criteria as "typical," and the other 52 patients were
      classified as having "atypical" intestinal Behcet's disease. Abdominal pain was
      the most common symptom (92%), followed by diarrhea and gastrointestinal
      bleeding. All of the 22 patients with a history of surgery had ulcers at the
      anastomotic site. Most of the patients, who had never been operated on, had
      lesions in the ileocecal area (96%). Sixty-three patients (67%) had a single
      ulcer. Many (76%) of the ulcers were larger than 1 cm, and the mean size of the
      ulcers was 2.9 cm. Most (99%) of the ulcers were round/oval or geographic in
      shape. Usually ulcers were deep (62%), and their margins discrete (80%). There
      was no difference in the endoscopic findings of typical and atypical intestinal
      Behcet's disease. Typical colonoscopic findings in intestinal Behcet's disease
      were single or a few deep ulcers with discrete margins in the ileocecal area or
      anastomotic site. Endoscopic characteristics of patients with intestinal
      involvement in the case of "suspect" or "possible" type of Behcet's disease that
      lack the systemic manifestations of Behcet's disease were in accord with those in
      "complete" or "incomplete" types of Behcet's disease, who fulfill the
      International Study Group for Behcet's Disease criteria.

PMID- 11515852
TI  - Cause of death in patients with inflammatory bowel disease.
AB  - BACKGROUND: Ulcerative colitis (UC) and Crohn's disease (CD) can both result in
      disease-related mortality. The aim of the present study was to analyze the
      comorbid medical conditions that contribute to death of patients with
      inflammatory disease. METHODS: The United States' vital statistics offer the
      opportunity to study causes of death broken down by primary and contributing
      secondary conditions. Deaths from UC and CD were retrieved from the 1991-1996
      data files of the National Center for Health Statistics. The strengths of
      individual associations between each comorbid condition and UC or CD were
      expressed as proportional mortality ratios, adjusted to the age-, gender-, and
      race-distribution of the general population. RESULTS: Deaths from UC and CD were
      found to be associated with a similar set of comorbid conditions and
      complications. Shock, volume depletion, protein/calorie malnutrition, and anemia
      were the most frequent comorbid conditions in the group of nutritional, fluid,
      and electrolyte disturbances. Both diseases were frequently associated with
      peritonitis and septicemia. Lastly, a large number of deaths were associated with
      complications following medical and surgical interventions. CONCLUSIONS: Deaths
      due to inflammatory bowel disease appear to be related to complications from
      multiple medical interventions and surgical procedures. In managing inflammatory
      bowel disease, the physician must keep in mind the potential for complications
      that may be associated with aggressive treatment.

PMID- 11515853
TI  - Granulomatous lung masses in an elderly patient with inactive Crohn's disease.
AB  - This is a case report of a 77-year-old female with Crohn's disease manifested by
      recurrent bowel obstructions, who required surgical resections on two occasions
      but no further medical treatment. She presented 2 years later with pulmonary
      infiltrates, hilar adenopathy, and multiple lung masses. Biopsies of the masses
      demonstrated noncaseating granulomatous inflammation and fibrosis similar to the
      pathology from her bowel resection. Six months later, these pulmonary lesions
      partially resolved without therapy. This case illustrates significant pulmonary
      manifestations of Crohn's disease in the absence of active gastrointestinal
      disease.

PMID- 11515854
TI  - Epidemiology of inflammatory bowel disease in Asia.
AB  - Studies of Asians in Asia show relatively low incidence rates for ulcerative
      colitis and Crohn's disease compared with North America and Europe. The
      prevalence of ulcerative colitis in migrant South Asians in Europe is similar to
      Europeans, whereas the prevalence of Crohn's disease for migrant South Asians in
      Europe is decreased compared with Europeans. The prevalence for both ulcerative
      colitis and Crohn's disease in Japan and Korea is relatively low. There are no
      obvious differences in age or sex distribution or rates of familial aggregation,
      and there are no significant differences in the clinical characteristics and
      natural history of ulcerative colitis and Crohn's disease in Asians compared with
      other racial groups with inflammatory bowel disease.

PMID- 11515855
TI  - The Nod2 gene in Crohn's disease: implications for future research into the
      genetics and immunology of Crohn's disease.
AB  - The association of the Nod2 gene on chromosome 16 with increased susceptibility
      to Crohn's disease holds the promise of catalyzing fundamental genetic and
      therapeutic advances. Coding region variants in the leucine-rich repeat region of
      Nod2 may affect host interactions with bacterial lipopolysaccharide. Genetic
      differences in pattern-recognition proteins (such as Nod2) of the innate immune
      system represent an increasingly important paradigm for understanding host
      environment interactions. The central problem for complex disease gene
      identification through genome-wide searches has been that of locus heterogeneity;
      it is hoped that this heterogeneity will recede with the identification of Nod2,
      as the first pieces of a puzzle accelerate placement of subsequent pieces. The
      potential for genetic approaches to positively impact the treatment of Crohn's
      disease and ulcerative colitis is unparalleled among complex, multigenic
      disorders.

PMID- 11515856
TI  - Chronic diarrhea: to scope or not to scope?

PMID- 11515857
TI  - Heparin in the treatment of inflammatory bowel disease: dare we take the risk?

PMID- 11515858
TI  - Prevention of colon cancer with ursodiol in ulcerative colitis.

PMID- 11515859
TI  - Receiver operating characteristic curve analysis of clinical risk models.
AB  - Receiver operating characteristic (ROC) curve analysis is a useful method to
      measure the ability of a clinical risk model to discriminate between hospital
      deaths and survivors. Its use in medicine originated as a method for synthesizing
      the specificity and sensitivity of diagnostic tests across a spectrum of possible
      cut points. The area under the ROC curve can be interpreted as a probability of
      correct classification or prediction. We illustrate its use in three steps:
      first, with a dichotomous variable to introduce specificity and sensitivity;
      next, with a categorical risk factor (surgical urgency) to produce a primitive
      ROC curve; and finally, with a continuous risk factor (age) to approximate the
      usual ROC curve used for clinical risk models.

PMID- 11515860
TI  - The National Emphysema Treatment Trial: a paradigm for future surgical trials.

PMID- 11515861
TI  - Paying the piper: the NETT strikes a sour note. National Emphysema Treatment
      Trial.

PMID- 11515862
TI  - Hospital volume is related to clinical and economic outcomes of esophageal
      resection in Maryland.
AB  - BACKGROUND: Previous studies have documented a relationship between hospital
      volume and perioperative and economic outcomes. Our objective was to determine
      the effect of hospital volume on outcomes of esophageal resection. METHODS:
      Statewide database was analyzed for patients who underwent esophageal resection
      in Maryland (n = 1,136 patients) from 1984 to 1999. Multivariate regression was
      used to determine the association of hospital volume with in-hospital mortality,
      length of stay, and charges after adjusting for case mix and time period.
      RESULTS: Unadjusted in-hospital mortality rates were lower in high volume
      hospitals (2.7%) than medium (12.7%) and low (16%) volume hospitals (p < 0.001).
      High hospital volume was associated with (1) fivefold reduction in the risk of
      death (odds ratio, 0.21; 95% confidence interval, 0.10 to 0.42; p < 0.001); (2) a
      6-day (95% confidence interval, 5 to 7 days; p < 0.001) reduction in length of
      stay; and (3) $11,673 (95% confidence interval, $9,504 to $12,841; p < 0.001)
      decrease in hospital charges. Conclusions. Hospitals that perform high volumes of
      esophageal resection have superior clinical and economic outcomes. By referring
      these patients to high volume centers, we may improve quality and reduce costs.

PMID- 11515863
TI  - Indications for using video-assisted thoracoscopic surgery to diagnose
      diaphragmatic injuries after penetrating chest trauma.
AB  - BACKGROUND: Video-assisted thoracoscopic surgery (VATS) has been shown to be an
      accurate method for identifying diaphragmatic injuries (DIs). The purpose of this
      investigation was to establish specific indications for the use of VATS after
      penetrating chest trauma. METHODS: A retrospective review of all patients
      undergoing VATS after penetrating chest trauma at a level 1 trauma center over an
      8-year period was performed. Logistic regression was used in an attempt to
      identify independent predictors of DI. RESULTS: One hundred seventy-one patients
      underwent VATS assessment of a hemidiaphragm, and 60 patients (35%) were found to
      have a DI. Five independent risk factors for DI were identified from analyzing
      the patient records: abnormal chest radiograph, associated intraabdominal
      injuries, high-velocity mechanism of injury, entrance wound inferior to the
      nipple line or scapula, and right-sided entrance wound. CONCLUSIONS: In the
      largest published series of patients undergoing VATS to exclude a DI, this review
      identifies five independent predictors of DI after penetrating chest trauma. A
      diagnostic algorithm incorporating these five factors was designed with the goal
      of reducing the number of unrecognized DIs after penetrating chest trauma by
      using VATS for patients at greatest risk for such injuries.

PMID- 11515864
TI  - Do patients with nonmetastatic non-small cell lung cancer demonstrate altered
      resting energy expenditure?
AB  - BACKGROUND: The cancer cachexia syndrome occurs in patients with non-small cell
      lung cancer (NSCLC) and includes elevated resting energy expenditure (REE). This
      increase in REE leads to weight loss, which in turn confers a poor prognosis.
      This study was undertaken to determine whether the cancer cachexia syndrome
      occurs in patients with nonmetastatic NSCLC. METHODS: In this case-control study,
      18 patients with nonmetastatic NSCLC (stages IA to IIIB) were matched to healthy
      controls on age (+/- 5 years), gender, and body mass index (+/- 3 kg/m2). Only 4
      cancer patients had experienced > 5% weight loss. Cancer patients and controls
      were compared on the basis of: (1) unadjusted REE, as measured by indirect
      calorimetry; (2) REE adjusted for lean body mass, as measured by dual x-ray
      absorptiometry; (3) REE adjusted for body cell mass, as measured by potassium-40
      measurement; and (4) REE adjusted for total body water, as measured by tritiated
      water dilution. RESULTS: We observed no significant difference in unadjusted REE
      or in REE adjusted for total body water. However, with separate adjustments for
      lean body mass and body cell mass, cancer patients manifested an increase in REE:
      mean difference +/- standard error of the mean: 140+/-35 kcal/day (p = 0.001) and
      173+/-65 kcal/day (p = 0.032), respectively. Further adjustment for weight loss
      yielded similarly significant results. CONCLUSIONS: These results suggest that
      the cancer cachexia syndrome occurs in patients with nonmetastatic NSCLC and
      raise the question of whether clinical trials that target cancer cachexia should
      be initiated before weight loss.

PMID- 11515865
TI  - Predictors of lymph node and intrapulmonary metastasis in clinical stage IA non
      small cell lung carcinoma.
AB  - BACKGROUND: The feasibility of limited surgical resection for clinical stage IA
      non-small cell lung cancer still remains controversial. METHODS: From July 1987
      through April 1998, 389 patients with clinical stage IA disease underwent major
      lung resection and complete mediastinal lymph node dissection. Univariate and
      multivariable analyses were performed to determine predictors of local or
      regional tumor spread: pathologic lymph node involvement, intrapulmonary
      metastases, and lymphatic invasion. RESULTS: Of the 389 patients, 88 (23%) had
      lymph node involvement or intrapulmonary metastases pathologically. According to
      multivariable analyses, grade of differentiation and pleural involvement were
      significant predictors of local or regional tumor spread (p < 0.01). Based on
      these results, more than 40% of clinical stage IA non-small cell lung cancer
      patients showed pathologic lymph node involvement or intrapulmonary metastases,
      or both, if the patients had both of the predictors of pathologic local or
      regional involvement: moderate or poor differentiation of the primary tumor and
      pleural involvement by tumor cells. CONCLUSIONS: Limited surgical resection is
      not feasible for clinical stage IA non-small cell lung cancer, especially when
      the tumor shows moderate or poor differentiation, or pleural involvement.

PMID- 11515866
TI  - Telescope anastomosis in bronchial sleeve resections with high-caliber mismatch.
AB  - BACKGROUND: The efficacy of bronchial telescope anastomosis was evaluated
      retrospectively in patients undergoing sleeve resections with high-caliber
      mismatch. METHODS: The hospital charts of patients undergoing upper and lower
      sleeve bilobectomy and lower lobe lobectomy with replantation of the middle lobe
      or upper lobe into the mainstem bronchus were retrospectively reviewed. Age, sex,
      side, TNM stage, preoperative forced expiratory volume in 1 second (FEV1 [%]),
      preoperative risk factors, postoperative course, survival (months), and causes of
      death were recorded. RESULTS: Fifteen patients suffering from bronchial carcinoma
      were operated on. In 6 cases FEV1 was less than 2 L (FEV1 49% to 80%, mean 64.3,
      median 61). Three patients were 70 years and older. There were 7 high-risk cases
      presenting with coronary heart disease (n = 3), chronic alcoholism (n = 3),
      cerebrovascular disease (n = 1), and active tuberculosis (n = 1). Local
      radicality was achieved in all patients but 1, in whom pneumonectomy was
      contraindicated. There was no postoperative mortality. Early complications
      consisted of 1 anastomotic dehiscence successfully closed with an intercostal
      flap and 1 patient with bilateral pneumonia requiring mechanical ventilation for
      5 days. One parenchymal fistula led to prolonged drainage; in 1 patient
      pneumothorax after removal of the chest tube required redrainage. There were no
      late complications, and no anastomotic stenosis developed. Survival ranged from
      12 to 56 months (median 29.8, mean 30, SD 15.7). Seven patients died between 3.9
      and 14 months postoperatively (mean 8.5, median 6.9) of intrabronchial local
      recurrence (n = 1), distant recurrence (n = 3), intrathoracic recurrence (n = 1),
      and nontumor-related causes (n = 2). CONCLUSIONS: Telescope anastomosis is a safe
      and efficient technique of bronchial sleeve resection.

PMID- 11515867
TI  - Pulmonary function, postoperative pain, and serum cytokine level after lobectomy:
      a comparison of VATS and conventional procedure.
AB  - BACKGROUND: Although lobectomy by the video-assisted thoracic surgical (VATS)
      approach is assumed to be less invasive than lobectomy by the standard
      posterolateral thoracotomy (PLT) approach, it has not been scientifically proven.
      METHODS: Twenty-two consecutive, nonrandomized patients, underwent either a VATS
      approach (n = 13) or a posterolateral thoracotomy approach (n = 9) to perform
      pulmonary lobectomy for peripheral lung cancers in clinical stage I. Pain and
      serum cytokines were measured until postoperative day (POD) 14. Pulmonary
      function tests were performed on POD 7 and POD 14. RESULTS: Postoperative pain
      was significantly less in the VATS group on PODs 0, 1, 7, and 14. Recovery of
      pulmonary function was statistically better in the VATS group. Negative
      correlations between the recovery rates of pulmonary function and postoperative
      pain were observed on POD 7. The serum interleukin-6 level in the PLT group was
      significantly elevated on POD 0 compared with the VATS group (posterolateral
      thoracotomy: 21.6+/-24.3 pg/mL; VATS: 4.1+/-7.9 pg/mL, p = 0.03). CONCLUSIONS:
      Lobectomy by the VATS approach generates less pain and cytokine production, and
      preserves better pulmonary function in the early postoperative phase.

PMID- 11515868
TI  - Resection and perfusion thermochemotherapy: a new approach for the treatment of
      thymic malignancies with pleural spread.
AB  - BACKGROUND: Thymoma and thymic carcinoma with pleural spread have a high rate of
      locoregional recurrence and poor prognosis. Maximal debulking coupled with
      aggressive local treatment could offer a chance for cure. This study evaluates
      the early and midterm results of operation and hyperthermic pleural perfusion
      with cisplatinum for thymic malignancies. METHODS: Fifteen patients (11 men), 20
      to 67 years old (10 thymoma, 4 thymic carcinoma, 1 carcinoma in thymic cyst)
      underwent resection and hyperthermic pleural perfusion between 1995 to 2000. All
      had pleural spread proven before or intraoperatively. Six of the thymoma cases
      were recurrent. Current operation included resection without pleurectomy (9
      patients), resection with pleurectomy (5), and extrapleural pneumonectomy (1
      patient) with intraoperative hyperthermic pleural perfusion in all. Intrapleural
      temperature reached 40.3 degrees C to 43 degrees C. The total dose of cisplatinum
      was 150 mg or more in 14 patients. RESULTS: Complete resection (R0) was achieved
      in 10 patients, subtotal (R1) in 3, and partial (R2) in 2. There was no operative
      mortality, no hemodynamic or respiratory disturbances during perfusion, and no
      hematologic, neurologic, or renal complications. Complications consisted of
      significant bleeding (2 patients), fever (2), and air leak (1 patient). Two
      patients with thymic carcinoma died after 27 and 34 months, and 1 is alive with
      no evidence of disease at 54 months. Two patients with thymoma died after 7 and
      36 months. Eight are alive after 9 to 70 months. Four patients (all R0) are alive
      without local recurrence more than 60 months after operation and hyperthermic
      pleural perfusion. CONCLUSIONS: Operation and thermochemotherpy is feasible and
      safe in patients with thymic tumors. This method seems to offer excellent local
      control for patients with stage IV-a thymic malignancies. Midterm results suggest
      that operation plus hyperthermic pleural perfusion may lengthen survival in stage
      IV-a thymoma.

PMID- 11515869
TI  - Enhancement of paclitaxel-mediated cytotoxicity in lung cancer cells by 17
      allylamino geldanamycin: in vitro and in vivo analysis.
AB  - BACKGROUND: It has previously been demonstrated that 17-allylamino geldanamycin
      (17-AAG) enhances paclitaxel-mediated cytotoxicity and downregulates vascular
      endothelial factor expression in non-small cell lung cancer. This project was
      designed to evaluate the tumoricidal and antiangiogeneic effects of 17-AAG and
      paclitaxel in H358 non-small cell lung cancer cells grown as xenografts in nude
      mice. METHODS: In vitro cytotoxic drug combination effects were evaluated by (4,
      5-dimethylthiazo-2-yl)-2, 5-diphenyl tetrazolium bromide-based proliferation
      assays. The combinations of 17-AAG and paclitaxel were administered
      intraperitoneally in nude mice bearing H358 tumor xenografts. Tumor volumes were
      measured weekly. Tumor expression of erbB2, vascular endothelial cell growth
      factor, von Willebrand factor (tumor microvasculature), and activated caspase 3
      (apoptosis) were determined by immunohistochemistry. RESULTS: Five- to 22-fold
      enhancement of paclitaxel cytotoxicity was achieved by paclitaxel + 17-AAG
      combination that was paralleled with marked induction of apoptosis. This
      combination treatment profoundly suppressed tumor growth and significantly
      prolonged survival of mice bearing H358 xenografts. Immunohistochemical staining
      of tumor tissues indicated profound reduction of vascular endothelial cell growth
      factor expression associated with reduction of microvasculature in tumors treated
      with 17-AAG. Apoptotic cells were more abundant in tumors treated with 17-AAG +
      paclitaxel than in those treated with 17-AAG or paclitaxel alone. CONCLUSIONS:
      Concurrent exposure of H358 cells to 17-AAG and paclitaxel resulted in
      supraadditive growth inhibition effects in vitro and in vivo. Analysis of
      molecular markers of tumor tissues indicated that therapeutic drug levels could
      be achieved with this chemotherapy regimen leading to significant biological
      responses. Moreover, 17-AAG-mediated suppression of vascular endothelial cell
      growth factor production by tumor cells may contribute to the antitumor effects
      of this drug combination in vivo.

PMID- 11515870
TI  - Epidermal growth factor receptor up-regulation is associated with lung growth
      after lobectomy.
AB  - BACKGROUND: We hypothesized that compensatory lung growth after lobectomy is
      characterized by a combination of cellular hyperplasia and hypertrophy and that
      up-regulation of epidermal growth factor receptor (EGFR) is involved in these
      processes. METHODS: Age-matched mature pigs were divided into four groups. The
      control group (group C) did not have operation. Two groups underwent left upper
      lobectomy and were studied 2 weeks (group L2) or 3 months (group L3) later. The
      last group underwent a sham left thoracotomy, and the left lower lobe was
      harvested 2 weeks later for EGFR analysis. Left lower lobes were studied using
      wet weight, cell proliferation index through immunostaining for 5-bromo-2'
      deoxyuridine, morphometry, and Western blot analysis for EGFR. Content of protein
      and DNA (deoxyribonucleic acid) in the lung tissue was also determined. RESULTS:
      Left lower lobe weights were elevated in both groups L2 and L3 compared with
      group C. We noted a significant rise in the proliferation index, with a
      concomitant increase in EGFR expression, in group L2 compared with group C. In
      group L3, there was an increase in the protein to DNA ratio compared with group
      C. CONCLUSIONS: We conclude that compensatory lung growth after lobectomy
      comprises an early increase in the cell proliferation index (ie, cellular
      hyperplasia) and a late increase in the protein to DNA ratio (ie, cellular
      hypertrophy). The early proliferative phase is associated with EGFR up
      regulation.

PMID- 11515872
TI  - Neonatal repair of truncus arteriosus: continuing improvement in outcomes.
AB  - BACKGROUND: Repair of truncus arteriosus in the neonatal and early infant periods
      has become standard practice at many centers. We reviewed our recent experience
      with repair of truncus arteriosus in neonates, with a focus on early and
      intermediate outcomes. METHODS: From July 1992 to December 1999, 65 patients 1
      month of age or less underwent primary complete repair of truncus arteriosus.
      Median age was 10 days, and median weight was 3.2 kg. Major associated anomalies
      included moderate or severe truncal valve regurgitation in 15 patients (23%),
      interrupted aortic arch in 8 (12%), coronary artery abnormalities in 12 (18%),
      and nonconfluence of the pulmonary arteries in 3 (5%). Median durations of
      cardiopulmonary bypass and cardioplegic arrest were 172 minutes and 90 minutes,
      respectively. Circulatory arrest was employed only in 7 patients undergoing
      concomitant repair of interrupted arch. Reconstruction of the right ventricular
      outflow tract was achieved with an aortic (n = 39) or pulmonary (n = 26)
      allograft valved conduit (median diameter, 12 mm). Replacement (n = 6) or repair
      (n = 5) of a regurgitant truncal valve was performed in 11 patients, and
      interrupted arch was repaired in 8. RESULTS: There were three early deaths (5%).
      Early reoperations included reexploration for bleeding in 3 patients, emergent
      replacement of a pulmonary outflow conduit that failed acutely in 1 patient, and
      placement of a permanent pacemaker in 1. Mechanical circulatory support was
      required in 1 patient. During the median follow-up of 32 months, there were two
      deaths. The Kaplan-Meier estimate of survival was 92% at 1 year and beyond. The
      only demographic, diagnostic, or operative factors significantly associated with
      poorer survival over time were operative weight of 2.5 kg or less (p = 0.01) and
      truncal valve replacement (p = 0.009). Actuarial freedom from conduit replacement
      among early survivors was 57% at 3 years. CONCLUSIONS: Repair of truncus
      arteriosus in the neonatal period can be performed routinely with excellent
      survival, even in patients with major associated abnormalities.

PMID- 11515871
TI  - Effect of endothelin receptor antagonist on lung allograft apoptosis and NOSII
      expression.
AB  - BACKGROUND: It is postulated that apoptosis contributes to ischemia-reperfusion
      graft dysfunction after lung transplantation. The purpose of this study was to
      determine whether the improvement in lung function that we previously observed
      with the use of an endothelin-1 (ET-1) receptor antagonist after ischemia
      reperfusion injury is associated with a reduction in inducible nitric oxide
      synthase (NOSII) expression and programmed cell death. METHODS: Left lung canine
      allotransplantation was performed. Harvested lung blocks were preserved with
      modified Eurocollins solution and stored at 4 degrees C for 18 to 20 hours. Lung
      allografts were tested for the expression of NOSII by immunohistochemistry, and
      extent of apoptosis by terminal dUTP nick end-labeling (TUNEL). Animals blindly
      received either an intravenous infusion of saline (control) or the ET-1 receptor
      antagonist (SB209670) (15 microg/kg/min). Infusion began 30 minutes
      pretransplantation and continued to 6 hours posttransplantation. RESULTS:
      Immunohistochemical analysis demonstrated significantly stronger NOSII
      immunostaining in the allografts of the saline control group (36.5%+/-3.6%)
      compared with native right lungs (6.9%+/-1.3%, p < 0.001) or the ET-receptor
      antagonist treatment group (9.6%+/-1.4%, p < 0.001). The TUNEL staining revealed
      a significantly stronger labeling in the allografts of the saline treatment
      control group (40.7%+/-6.2%) compared with native right lungs (5.0%+/-0.6%, p <
      0.005) or the ET receptor antagonist treatment group (14.1%+/-2.8%, p < 0.01).
      CONCLUSIONS: We conclude that treatment of lung allografts with the ET-1 receptor
      antagonist SB209670 reduces the area of NOSII expression and the extent of
      apoptosis, factors known to contribute to the process of prolonged ischemia
      reperfusion injury.

PMID- 11515873
TI  - Surgical management of severe truncal insufficiency: experience with truncal
      valve remodeling techniques.
AB  - BACKGROUND: Truncal valve insufficiency has been a significant short- and long
      term risk factor for repair of truncus arteriosus. Recent reports have documented
      the virtues of truncal valve repair. The purpose of this report is to review our
      experience with truncal valve repair and illustrate our techniques. METHODS:
      Between 1995 and 2000, 8 patients had interventions for severe truncal valve
      insufficiency at primary repair (3 patients) or in conjunction with conduit
      replacement (5 patients). One neonate had truncal valve replacement at initial
      repair early in the experience. The other 7 patients had truncal valve repair, 3
      by valvar suture techniques. The remaining 4 patients had leaflet excision and
      annular remodeling in 3 (coronary reimplantation was required in 2) and
      commissure resuspension in 1 patient. RESULTS: Trivial to mild truncal valve
      insufficiency is present in the patients who had leaflet excision and annular
      remodeling (n = 3) and commissure resuspension (n = 1). Of the 3 patients who had
      valvar suture truncal valve repair, there was one death and 2 patients required
      acute valve replacement. The 7 survivors are doing well 1 month to 6 years
      postoperatively. CONCLUSIONS: Truncal valve repair by valvar suture techniques
      has not been successful in our practice. Truncal valve remodeling by leaflet
      excision and reduction annuloplasty is an effective method for truncal valve
      repair. When leaflet excision of a coronary sinus of Valsalva is required,
      coronary artery translocation can be accomplished.

PMID- 11515874
TI  - Regional low-flow perfusion provides somatic circulatory support during neonatal
      aortic arch surgery.
AB  - BACKGROUND: Regional low-flow perfusion has been shown to provide cerebral
      circulatory support during neonatal aortic arch operations. However, its ability
      to provide somatic circulatory support remains unknown. METHODS: Fifteen neonates
      undergoing arch reconstruction with regional perfusion were studied. Three
      techniques were used to assess somatic perfusion: abdominal aortic blood
      pressure, quadriceps blood flow (near-infrared spectroscopy), and gastric
      tonometry. RESULTS: Twelve patients required operation for hypoplastic left heart
      syndrome, and 3 required arch reconstruction with a biventricular repair. There
      was one death (7%). Abdominal aortic blood pressure was higher (12+/-3 mm Hg
      versus 0+/-0 mm Hg), and quadriceps blood volumes (5+/-24 versus -17+/-26) and
      oxygen saturations (57+/-25 versus 33+/-12) were greater during regional
      perfusion than during deep hypothermic circulatory arrest (p < 0.05). During
      rewarming, the arterial-gastric mucosal carbon dioxide tension difference was
      lower after circulatory arrest than after regional perfusion (-3.3+/-0.3 mm Hg
      versus 7.8+/-7.6 mm Hg, p < 0.05). CONCLUSIONS: Regional low-flow perfusion
      provides somatic circulatory support during neonatal arch surgical procedures.
      Support of the subdiaphragmatic viscera should improve the ability of neonates to
      survive the postoperative period.

PMID- 11515875
TI  - Aortopulmonary collateral flow in the Fontan patient: does it matter?
AB  - BACKGROUND: The effects of aortopulmonary collaterals (APCs) on the outcome of a
      Fontan procedure are unclear. We undertook this study to define the incidence and
      extent of APC flow, identify risk factors for APC flow, and determine if APC flow
      has a measurable effect on the outcome of a Fontan procedure. METHODS: The APC
      flow was directly measured in 32 patients undergoing Fontan procedures from July
      1997 to September 2000. The APC flow was measured in the operating room during
      total cardiopulmonary bypass, and was expressed as a percentage of total bypass
      pump flow. RESULTS: The APC flow ranged from 9% to 49% of total pump flow
      (median, 18%). Higher preoperative systemic oxygen saturation, pulmonary artery
      oxygen saturation, pulmonary to systemic flow ratio, and angiographic APC grade
      correlated with higher APC flow. There were no operative deaths; there was one
      Fontan takedown (APC flow = 14%). The APC flow had no significant effects on
      postoperative Fontan pressure, common atrial pressure, transpulmonary gradient,
      duration of effusions, or resource utilization after the Fontan procedures.
      CONCLUSIONS: In patients undergoing a Fontan procedure, APC flow is omnipresent,
      although its extent varies widely. Increased APC flow has no significant effect
      on the outcome of a Fontan procedure. This conclusion applies to patients who are
      well prepared for a Fontan procedure, but may not extend to patients at higher
      risk.

PMID- 11515876
TI  - Outcomes of intraoperative device closure of muscular ventricular septal defects.
AB  - BACKGROUND: The surgical management of muscular ventricular septal defects (mVSD)
      in the small infant is a challenge particularly when multiple and associated with
      complex cardiac lesions. Devices for percutaneous implantation have the advantage
      of ease of placement and for the double umbrella designs a wide area of coverage.
      We reviewed our experience and clinical outcomes of intraoperative mVSD device
      closure for such defects in small infants. METHODS: Since October 1989,
      intraoperative VSD device closure was a component of the surgical strategy in 14
      consecutive patient implants (median age, 5.5 months; range, 3 to 11 kg), whose
      defects were thought difficult to approach using conventional techniques. Nine
      patients had associated complex cardiac lesions, 10 multiple mVSDs, and 4
      patients had a previous pulmonary artery banding. RESULTS: There were 2 early
      deaths, 1 in a severely ill child who preoperatively had pulmonary hypertension
      and left ventricular failure and another in a patient with a hypoplastic left
      heart. Mean pulmonary to systemic flow ratio before device insertion was 3.5:1.
      Complete closure was achieved in 5 patients and clinically insignificant residual
      shunts persisted in 7. In 2 infants with significant residual lesions concomitant
      pulmonary artery banding was required. Postoperative mean pulmonary to systemic
      flow ratio was 1.7:1. In follow-up of the 12 surviving infants (mean, 41 months),
      8 had complete closure and 3 persistent residual shunts. One patient with no
      residual shunting required heart transplantation for progressive ventricular
      failure 9 years after operation. All devices were well positioned on
      postoperative echocardiograms. There was 1 late death due to aspiration in a
      patient with a tiny residual shunt. CONCLUSIONS: Infants requiring operative
      intervention with mVSDs are difficult to manage and have an increased mortality
      and morbidity. Intraoperative VSD device placement for closure of mVSDs is
      feasible, can avoid ventriculotomy, division of intracardiac muscle bands, and is
      ideally suited for the neonate or infant.

PMID- 11515877
TI  - Anatomically corrective repair of complete atrioventricular septal defects and
      major cardiac anomalies.
AB  - BACKGROUND: Although satisfactory results of corrective surgery for
      atrioventricular septal defects (AVSDs) with complex lesions such as double
      outlet right ventricle (DORV) or atrial isomerism have been reported in recent
      years, the optimal surgical options for isomerism hearts is still a controversial
      issue. METHODS: We performed anatomically corrective repair on 13 children with
      balanced forms of complete AVSDs and associated major cardiac anomalies. Eight of
      the 13 patients had atrial isomerism (right in 1, left in 7), 5 of whom had DORV.
      Four others had DORV with trisomy 21, and 1 had tetralogy of Fallot. Atrial
      septation for isomerism with the placement of an additional prosthesis was
      performed on 4 patients. RESULTS: Two hospital deaths and one late death occurred
      only in the isomerism group. Three reoperations were required solely in the left
      isomerism group: one replacement of the valved external conduit concomitantly
      with reconstruction of the left ventricular outflow obstruction, one mitral valve
      replacement for severe regurgitation of left atrioventricular valve, and one
      relief of progressing left ventricular outflow obstruction. CONCLUSIONS: The
      results of anatomically corrective surgery for AVSDs with major associated
      cardiac anomalies in the nonisomerism group were excellent. The optimal surgical
      options for isomerism heart, however, remain a controversial issue.

PMID- 11515878
TI  - Direct closure of ostium primum defect in the repair of atrioventricular septal
      defect.
AB  - BACKGROUND: Patch closure is generally performed for atrial septation of an
      atrioventricular septal defect. We recently developed a new surgical technique
      for repairing atrioventricular septal defects that avoids the use of any patch
      material for closing the atrial septal defect. We report our experience with this
      procedure. METHODS: Seven patients (complete type: 5, partial type: 2) underwent
      this new operation. The diameters of the atrial septal defects were measured by
      transesophageal echocardiography. The preoperative electrocardiograms were
      compared with those taken after the operations. RESULTS: Diameters of the atrial
      defects ranged from 3 to 10 mm. Electrocardiograms before and after the
      operations did not change. No significant atrioventricular valve regurgitation
      and no residual shunts were detected by postoperative echocardiography.
      CONCLUSIONS: This method simplifies the repair of atrioventricular septal
      defects. In the short-term results, no arrhythmia and no valve regurgitation was
      seen.

PMID- 11515879
TI  - Vascular anomalies and tracheoesophageal compression: a single institution's 25
      year experience.
AB  - BACKGROUND: Vascular rings are uncommon anomalies in which preferred strategies
      for diagnosis and treatment may vary among institutions. In this report, we offer
      a description of our approach and a review of our 25-year experience. METHODS: A
      retrospective review was conducted of all pediatric patients with symptomatic
      tracheoesophageal compression secondary to anomalies of the aortic arch and great
      vessels diagnosed from 1974 to 2000. RESULTS: Thirty-one patients (38%) of eighty
      two patients (mean age, 1.7 years), were identified with double aortic arch, 22
      patients (27%) with right arch left ligamentum, and 20 patients (24%) with
      innominate artery compression. Our diagnostic approach emphasized barium
      esophagram, along with echocardiography. This regimen was found to be reliable
      for all cases except those with innominate artery compression for which
      bronchoscopy was preferred, and except those with pulmonary artery sling for
      which computed tomography or magnetic resonance imaging, in addition to
      bronchoscopy, were preferred. Left thoracotomy was the most common operative
      approach (70 of 82; 85%). Ten patients (12%) had associated heart anomalies, and
      6 (7%) patients underwent repair. Complications occurred in 9 (11%) patients and
      led to death in 3 (4%) patients. CONCLUSIONS: In our practice, barium swallow and
      echocardiography are sufficient in diagnosing and planning the operative strategy
      in the majority of cases, with notable exceptions. Definitive intraoperative
      delineation of arch anatomy minimizes the risk of misdiagnosis or inadequate
      treatment.

PMID- 11515881
TI  - Purely internal thoracic artery grafts: outcomes.
AB  - BACKGROUND: Most of our patients with coronary artery disease have undergone
      bypass exclusively with purely internal thoracic artery grafts (PITA). Our goal
      has been to lengthen the time a patient benefits from coronary bypass operations.
      The present report describes an 8.5-year study of outcomes including mortality
      and the need for reintervention in patients who have undergone bypass with PITA.
      METHODS: We studied 897 patients who underwent PITA with a total of 3,784
      internal thoracic artery (ITA) grafts (4.2 grafts per patient). Connecting ITA to
      ITA along with sequential anastomosis made the procedure possible. RESULTS: Early
      mortality for the group was 2.3%. Freedom from death was 86% and freedom from
      reintervention was 94% at 5 years after the operation. CONCLUSIONS: The
      acceptable early and late mortality and the 94% freedom from reintervention as
      long as 8.5 years after operation in this group of patients inspire us to
      continue choosing PITA for patients with three-vessel coronary artery disease.

PMID- 11515880
TI  - Long-term outcomes after cardiac transplantation: an experience based on
      different eras of immunosuppressive therapy.
AB  - BACKGROUND: Constantly changing practices in heart transplantation have improved
      posttransplant survival in patients with end-stage heart disease. The objective
      of this study was to evaluate long-term outcomes in different eras of
      immunosuppressive therapy after cardiac transplantation at a single center during
      a two-decade period. METHODS: A retrospective review of 1,086 consecutive cardiac
      allograft recipients who underwent transplantation between 1977 to 1999 was
      performed. Patients were divided into four eras based on type of
      immunosuppressive therapy: era 1 = steroids, azathioprine (n = 26, February 1977
      to March 1983), era II = steroids, cyclosporine (n = 43, April 1983 to April
      1985), era III = cyclosporine, steroids, azathioprine (n = 752, April 1985 to
      December 1995), era IV = cyclosporine, steroids, mycophenolate mofetil (n = 315,
      January 1996 to October 1999). RESULTS: The actuarial survival of the entire
      cohort of 1,086 patients undergoing cardiac transplantation was 79%, 66%, and 49%
      at 1, 5, and 10 years, respectively. There were significant trends in recipient
      age and gender distribution among the four eras with increasing proportion of
      older age (> 60 years) and female recipients in eras III and IV (p = 0.001 and
      0.02). Early mortality and long-term survival improved significantly over all
      eras (p < 0.001). Rejection as a cause of death decreased over time (era I, 24%;
      era II, 21%; era III, 15%; era IV, 9%; p = 0.02), whereas the contribution of
      transplant coronary artery disease as a cause of death remained unchanged.
      CONCLUSIONS: Cardiac transplantation provides satisfactory long-term survival for
      patients with end-stage heart failure. The improving outcomes in survival
      correlate with improved immunosuppressive therapy in each era. Although the
      reasons for improvement in survival over time are multifactorial, we believe that
      changes in immunosuppressive therapy have had a major impact on survival as
      evidenced by the decreasing number of deaths due to rejection.

PMID- 11515882
TI  - Myocardial revascularization with and without cardiopulmonary bypass in
      multivessel disease: impact of the strategy on early outcome.
AB  - BACKGROUND: The impact of myocardial revascularization without cardiopulmonary
      bypass (CPB) was evaluated in a series of consecutive patients with multivessel
      disease. METHODS: From May 21, 1997 to November 30, 2000, 1,843 consecutive
      patients underwent isolated myocardial revascularization. From this total, 919
      patients were done without CPB (group A, 49.9%) and 924 patients were done with
      CPB (group B, 50.1%). Patients that converted from without CPB to with CPB were
      included in group A. Thirty-three variables were evaluated with univariate and
      multivariate analysis to identify the independent variables predictive of higher
      incidence of early mortality, acute myocardial infarction, cerebrovascular
      accident, and early major events. RESULTS: Early mortality was 2.2% (group A,
      1.4%; group B, 3.0%; p = 0.016), acute myocardial infarction incidence was 1.8%
      (group A, 1.1%; group B, 2.6%; p = 0.027), cerebrovascular accident incidence was
      0.9% (group A, 0.8%; group B, 1.0%; p = not significant), and early major events
      incidence was 6.7% (group A, 5.3%; group B, 8.2%; p < 0.001). Stepwise logistic
      regression analysis showed that CPB was an independent risk factor for higher
      mortality (odds ratio, 2.2; p = 0.0217), higher incidence of acute myocardial
      infarction (odds ratio, 2.5; p = 0.0185), and higher incidence of early major
      events (odds ratio, 1.8, p = 0.0034). CONCLUSIONS: When CPB was not used,
      patients experienced lower early mortality and incidences of acute myocardial
      infarction were less complicated, both at univariate analysis and stepwise
      logistic regression analysis.

PMID- 11515883
TI  - Radial artery for myocardial revascularization: long-term clinical and
      angiographic results.
AB  - BACKGROUND: To evaluate the long-term clinical and angiographic results of the
      radial artery (RA) as a graft in coronary artery bypass surgery. METHODS: One
      hundred sixty-four patients had a RA graft from July 1992 to July 1994. In 128
      (group A) the RA was connected end to side (115) or end to end (13) to the left
      internal mammary artery. In 36 (group B) the proximal anastomosis was on the
      ascending aorta. RESULTS: Early mortality was 1.8% (group A 1.6% and group B
      2.8%). Eight-year survival was 83.2%+/-3.2% (group A 82.1%+/-3.8% and group B
      86.7%+/-6.2%, p = not significant [NS]), and event free survival was 80.1%+/-3.5%
      (group A 79.9%+/-4.4% and group B 80.2%+/-7.3%, p = NS). Sixty-one patients
      (37.2%) had an early angiography within 90 days from the operation. Patency rate
      of RA distal anastomoses were 98.9% (88 of 89), 98.7% in group A (77 of 78), 100%
      in group B (11 of 11; p = NS). After a mean of 48+/-27 months (6 to 96), 72
      patients (51.1% of the survivors) had a new angiography. Patency rate of RA
      distal anastomoses was 95.6% (87 of 91), 93.8% in group A (61 of 65) and 100% in
      group B (26 of 26; p = NS). All the intermediate RA-LIMA anastomoses were patent
      at the early and late control. Patency rate for RA and IMAs was similar both
      early (88 of 89 versus 82 of 82; p = NS) and after 48+/-27 months (87 of 91
      versus 93 of 93; p = NS). CONCLUSIONS: Long-term clinical results after RA
      grafting are satisfying. Angiographic patency rate, both early and after 48
      months, is higher than 90% and is similar to that obtained with internal mammary
      arteries. The site of the proximal anastomosis does not influence early and late
      patency.

PMID- 11515884
TI  - Tranexamic acid in off-pump coronary surgery: a preliminary, randomized, double
      blind, placebo-controlled study.
AB  - BACKGROUND: We evaluated the hemostatic effects of tranexamic acid, a synthetic
      antifibrinolytic drug, in patients undergoing beating-heart coronary surgery.
      METHODS: Forty consecutive patients were in a double-blind manner, prospectively
      randomized into two groups: 20 patients received tranexamic acid (bolus of 1 g
      before skin incision, followed by continuous infusion of 400 mg/hr during
      surgery), and 20 patients received saline. As primary outcomes, bleeding and
      allogeneic transfusions were considered. D-dimer and fibrinogen plasma levels
      were also evaluated to monitor the activation of fibrinolysis. Major
      postoperative thrombotic events, as a potential consequence of antifibrinolytic
      treatment, were recorded. RESULTS: The treatment group had significantly lower
      postoperative bleeding (median [25th to 75th percentiles]: 400 mL [337 to 490 mL]
      vs 650 ml [550 to 862 mL], p < 0.0001), lower need for allogeneic blood products
      (1,200 vs 5,300 mL, p < 0.001), and lower postoperative D-dimer plasma levels. No
      postoperative thrombotic complications were observed in either group.
      CONCLUSIONS: In this initial series of patients undergoing off-pump coronary
      surgery, tranexamic acid appears to be effective in reducing postoperative
      bleeding and the need for allogeneic blood products.

PMID- 11515885
TI  - Reversal of preexisting vasospasm in coronary artery conduits.
AB  - BACKGROUND: To reverse preexisting coronary graft spasm, we investigated the
      vasodilative effect of the average therapeutic plasma concentration of
      nitroglycerin (NTG) alone and various calcium antagonists in combination with NTG
      in human arterial and venous conduits. METHODS: Vasodilative effects of 2 x 10(
      8) mol/L NTG alone and 10(-8) mol/L NTG in combination with 2.2 x 10(-7) mol/L
      diltiazem, 2.8 x 10(-7) mol/L nifedipine, 10(-7) mol/L verapamil, or 5.6 x 10(-8)
      mol/L nicardipine were assessed in human radial artery, internal thoracic artery,
      and saphenous vein segments precontracted with a mixture of ten times the maximum
      plasma concentrations of endothelin-1 (8.6 x 10(-13) mol/L), angiotensin II (36 x
      10(-11) mol/L), 5-hydroxytryptamine (3.4 x 10(-7) mol/L), and norepinephrine (1.7
      x 10(-8) mol/L). The studies were done in organ baths. RESULTS: The therapeutic
      concentration of NTG alone or nifedipine, verapamil, diltiazem, or nicardipine in
      combination with NTG caused equal relaxation in a particular group of vascular
      segments (average vasodilation: radial artery, 83% to 95% [p = 0.7608 by analysis
      of variancel; saphenous vein, 47% to 70% [p = 0.3142]; internal thoracic artery,
      54% to 79% [p = 0.27831). These combinations were not equally effective when
      compared between different groups of vascular segments (vasodilation; radial
      artery > internal thoracic artery > saphenous vein [p < 0.0001 by analysis of
      variance]). Although not significant, in comparison with NTG alone, NTG in
      combination with a calcium antagonist caused less vasodilation in any group of
      vascular segments. CONCLUSIONS: Nitroglycerin alone or in combination with
      nifedipine, verapamil, diltiazem, or nicardipine effectively reverses preexisting
      vasospasm in coronary artery conduits.

PMID- 11515886
TI  - Descending thoracic aortic aneurysm: surgical approach and treatment using the
      adjuncts cerebrospinal fluid drainage and distal aortic perfusion.
AB  - BACKGROUND: Neurologic deficit (paraplegia or paraparesis) remains a significant
      morbidity in the repair of descending thoracic aortic aneurysm. METHODS: Between
      February 1991 and February 2000, we operated on 182 patients for descending
      thoracic aortic aneurysm. For the purpose of this study-to identify the impact of
      the combined adjuncts distal aortic perfusion and cerebrospinal fluid (CSF)
      drainage on neurologic outcome-we selected the 148 of 182 nonemergent patients
      who had received conventional treatment (simple cross-clamping with or without
      adjuncts). The mean patient age was 61 years, and 49 of the 148 (33%) patients
      were women. Nine of the 148 patients (6%) had acute type B dissections. We
      compared the results of 105 of the 148 patients (71%) who received the combined
      adjuncts of CSF drainage and distal aortic perfusion with the remaining 43 (29%)
      patients who underwent repair using the simple cross-clamp with or without the
      addition of a single adjunct. RESULTS: Overall 30-day mortality was 13 of 148
      patients (8.8%). Overall early neurologic deficit was 4 of 148 (2.7%): 1 of 105
      (0.9%) patients who had received distal aortic perfusion and CSF drainage, versus
      3 of 43 (7%) in all other patients (p < 0.04). CONCLUSIONS: In our practice the
      use of the combined adjuncts of CSF drainage and distal aortic perfusion has all
      but eliminated the incidence of immediate postoperative neurologic deficit in
      nonemergent patients with aneurysms of the descending thoracic aorta.

PMID- 11515887
TI  - Opening and closing characteristics of the aortic valve after valve-sparing
      procedures using a new aortic root conduit.
AB  - BACKGROUND: The durability of aortic valve-sparing procedures is negatively
      affected by increased leaflet stress in the absence of normally shaped sinuses of
      Valsalva. We compared valve motion after remodeling procedures using a standard
      conduit and a specifically designed aortic root conduit. METHODS:
      Echocardiographic studies of the aortic valve dynamics were performed in 14
      patients after remodeling of the aortic root (7 standard conduits, group A; 7 new
      conduits, group B) and in 7 controls (group C). Opening and closing leaflet
      velocities and percent of slow closing leaflet displacement were measured. Root
      distensibility and the pressure strain of the elastic modulus were measured at
      all root levels. RESULTS: Root distensibility and the pressure strain of the
      elastic modulus were different in group A and B only at the sinuses (p < 0.001).
      Opening and closing leaflet velocities were not different among groups. Slow
      closing leaflet displacement was markedly more evident in group B patients
      (24.2%+/-1.9% versus 2.5%+/-1.9% in group A, p < 0.001) and similar to controls
      (22.1%+/-7.9%). CONCLUSIONS: The new conduit guarantees dynamic features of the
      aortic valve leaflets superior to those obtained with standard conduits and more
      similar to normal subjects.

PMID- 11515888
TI  - Experience with spiral computed tomography as the sole diagnostic method for
      traumatic aortic rupture.
AB  - BACKGROUND: Spiral computed tomographic (CT) scan is an excellent screen for
      aortic trauma. Traditionally, aortography is performed when injury is suspected
      to confirm the diagnosis. We hypothesized that it is safe and expeditious to
      forgo aortography when the spiral CT demonstrates aortic injury. METHODS:
      Retrospective review of 54 patients undergoing aortic repair from July 1994 to
      December 1999. Spiral CT was the initial diagnostic study in 52 patients.
      Pseudoaneurysm or aortic wall defect in the presence of mediastinal hematoma was
      considered diagnostic. Angiography, initially routine, was later performed only
      when requested by the surgeon, and for all "nonnegative" studies (periaortic
      hematoma without detectable aortic injury). RESULTS: Twenty-six patients
      underwent angiography before operation (group 1). Nineteen group 1 spiral CTs
      were unequivocally diagnostic; 7 were nonnegative and angiography was required.
      Twenty-eight other patients underwent repair based on spiral CT alone (group 2).
      There was one false-positive result in both groups. There were no unexpected
      operative findings. Mean time from admission to diagnosis was 5.7+/-3.4 hours for
      group 1 and 1.7+/-1.7 hours for group 2 (p < 0.01). CONCLUSIONS: Operating on the
      basis of a diagnostic spiral CT is safe and expeditious. Aortography may be
      reserved for those with equivocal studies.

PMID- 11515889
TI  - Cerebral oxygenation monitoring for total arch replacement using selective
      cerebral perfusion.
AB  - BACKGROUND: This study was undertaken to verify the safety of our total arch
      replacement assisted by selective cerebral perfusion with respect to cerebral
      oxygenation. METHODS: Subjects to be evaluated were selected between February
      1999 and March 2000 and comprised 13 patients who underwent total arch
      replacement (TAR) (TAR group) and 18 patients who had undergone coronary artery
      bypass grafting or valve replacement (control group). They were monitored
      throughout the operation by two-channel near-infrared spectroscopy. Changes in
      intracranial oxyhemoglobin and the tissue oxygenation index were compared between
      the two groups. Additionally, jugular venous oxygen saturation was simultaneously
      measured in 10 patients from each group. Maximum changes in these variables from
      baseline in the TAR group were compared with those in the control group.
      Bilateral oxygenation differences between two hemispheres were also evaluated.
      RESULTS: There was no incidence of postoperative cerebral infarction, and no
      significant difference was observed in the maximum decrease in these variables
      between the two groups. Bilateral oxygenation differences between the two
      hemispheres in the TAR group were similar to those in the control group, except
      for the tissue oxygenation index in the rewarming phase. CONCLUSIONS: From the
      standpoint of cerebral oxygenation, our technique of total arch replacement was
      nearly as safe as an ordinary cardiac operation.

PMID- 11515890
TI  - Role of biologic glue repair of proximal aortic dissection in the development of
      early and midterm redissection of the aortic root.
AB  - BACKGROUND: Redissection of the aortic root after supracommissural aortic graft
      replacement with reapproximation of the layers of the dissected aortic root is
      relatively rare. Causes and surgical treatment of this lesion remain
      controversial. METHODS: From January 1983 to September 2000, 130 patients had
      emergency operation for acute type A aortic dissection. Of them, 57 patients
      underwent root reconstruction using biologic glues and 4 patients (7.0%)
      developed redissection of the aortic root associated with moderate to severe
      aortic regurgitation 5 to 27 months after the initial operation. In all patients,
      the proximal false lumen was obliterated with infusion of gelatin-resorcinol
      formaldehyde (GRF) glue or BioGlue and the aorta was reinforced with Teflon felt
      strip or Surgicel placed on its outside wall. RESULTS: During reoperation, the
      noncoronary aortic sinus was found to be redissected in all patients with the
      dissection extending retrogradely to the aortic annulus. This resulted in aortic
      regurgitation with prolapse of the noncoronary cusp because the proximal suture
      line dehisced. Histopathology showed disappearance of the nuclei of the medial
      smooth muscle cells, suggesting tissue necrosis at the site of GRF glue
      application. The lesions were treated successfully with full root replacement
      using a freestyle heterograft bioprosthesis or a composite graft prosthesis.
      CONCLUSIONS: The use of biologic glues for reapproximating the layers of the
      dissected aortic root is associated with a certain amount of risk of aortic wall
      necrosis. Therefore, care should be taken to ensure proper use of these glues.
      Full root replacement could be a preferable technique for treating redissection
      of the aortic root.

PMID- 11515891
TI  - Impact of active monitoring of infection control practices on deep sternal
      infection after open-heart surgery.
AB  - BACKGROUND: Deep-sternal infection is a devastating complication after open-heart
      surgery. However, the association between infection control practices and deep
      sternal infection rates is unclear. METHODS: To identify contributors to
      increased deep-sternal infection rates in our institution, consecutive open-heart
      surgery patients were prospectively studied during two periods (75 and 40 days),
      including 66 and 40 patients, respectively. Active monitoring including 149
      infection control practices was performed in the operating room and intensive
      care unit. End-points were deep-sternal infection rates and their relation to
      infection control practices. RESULTS: Mean age was 62+/-11 years and 68% were
      males. Coronary bypass was performed in 82%. Clinical and surgical features were
      comparable, except that patients in period 2 were more likely to have heart
      failure (15% vs 1.5%, p = 0.01) and had a longer mean duration of surgery (277 vs
      217 minutes, p < 0.005). Only 57 practices (38%) were adequately performed. The
      main categories showing inadequate practices were disinfection, traffic, hand
      washing, and surgical attire of nonscrubbed personnel, anesthesiologists, and
      pump technicians. Many categories showed a statistically significant improvement
      between periods. Deep-sternal infection rates in prestudy and poststudy periods
      were 10% and 2.8%, respectively (p = 0.007). CONCLUSIONS: Active monitoring among
      personnel involved in open-heart surgery resulted in a significant and sustained
      decrease in deep-sternal infection rates, through modification of human behavior
      and improvement of performance standards, probably mediated by the Hawthorne
      effect. Periodic active monitoring may be a valuable tool to achieve and even
      sustain such a decrease with tremendous implications on morbidity, costs, and
      quality of care.

PMID- 11515892
TI  - Postoperatively administered aprotinin or epsilon aminocaproic acid after
      cardiopulmonary bypass has limited benefit.
AB  - BACKGROUND: Intraoperative antifibrinolytic treatment with aprotinin and epsilon
      aminocaproic acid (EACA) has been shown to be effective prophylaxis in the
      reduction of excessive bleeding after cardiopulmonary bypass operations. This
      study investigated the effectiveness of both drugs when used as a postoperative
      treatment of patients showing early signs of increased bleeding. METHODS: In a
      double-blind, randomized study, 69 patients with chest drainage of 100 mL or more
      1 hour after bypass were treated with aprotinin, EACA, or placebo. RESULTS: In
      the first 24 hours postoperatively, neither drug significantly reduced chest
      drainage or blood transfusion requirements compared with placebo. Median
      (interquartile) cumulative chest drainage volumes for the first 24 hours
      postoperatively for the aprotinin, EACA, and placebo groups were 525 (340, 750),
      575 (450, 762), and 650 (550, 800) mL, respectively. Among the study patients, 4
      undergoing valve operation and treated with aprotinin showed a trend toward less
      bleeding during the first 12 hours postoperatively compared with 5 valve
      operation patients who received placebo (p = 0.06). Among all patients, the
      treatment with aprotinin or EACA failed to reduce levels of D-dimer compared with
      placebo after treatment, indicating that fibrinolysis was not significantly
      inhibited. CONCLUSIONS: Aprotinin or EACA administered in the early postoperative
      period was ineffective in reducing postoperative bleeding with the exception of a
      small group of patients having valve operations in whom aprotinin treatment may
      have shown some benefit.

PMID- 11515893
TI  - Albumin versus hydroxyethyl starch in cardiopulmonary bypass surgery: a meta
      analysis of postoperative bleeding.
AB  - BACKGROUND: This meta-analysis tested the hypothesis that cumulative blood loss
      during the first 24 hours after cardiopulmonary bypass is lower in patients
      exposed to albumin than hydroxyethyl starch (HES). METHODS: Randomized controlled
      trials comparing albumin and HES in cardiopulmonary bypass patients were
      identified by bibliographic database searches and other methods. RESULTS: Sixteen
      trials involving 653 randomized patients were included. In 88% of randomized
      comparisons, postoperative bleeding was lower in the albumin group, and the
      standardized mean difference in bleeding favoring albumin across all trials (
      0.24; 95% confidence interval, -0.40 to -0.08) was statistically significant.
      Bleeding differences between albumin and either high or medium molecular weight
      HES were similar. In trials of adults, the pooled mean blood loss in the albumin
      group was 693+/-350 mL compared with 789+/-487 mL in the HES group. The estimated
      proportion of adult albumin group patients with blood loss of more than 1,000 mL
      was 19% compared with 33% of adult HES group patients. Conclusions. Postoperative
      blood loss is significantly lower in cardiopulmonary bypass patients exposed to
      albumin than HES.

PMID- 11515894
TI  - Influence of anterior mitral leaflet second-order chordae on leaflet dynamics and
      valve competence.
AB  - BACKGROUND: Chordal transposition is used in mitral valve repair, yet the effects
      of second-order chord transection on valve function have not been extensively
      studied. We evaluated leaflet coaptation, three-dimensional anterior mitral valve
      leaflet shape, and valve competence after cutting anterior second-order chordae.
      METHODS: In 8 sheep radiopaque markers were affixed to the left ventricle, mitral
      annulus, and leaflets. Animals were studied immediately with biplane
      videofluoroscopy and echocardiography before (Control) and after (Cut2) severing
      two anterior second-order "strut" chordae. Leaflet coaptation was assessed as
      separation between leaflet edge markers in the midleaflet and near each
      commissure (anterior commissure, posterior commissure). Anterior leaflet geometry
      was determined 100 milliseconds after end-diastole from three-dimensional
      coordinates of 13 markers. RESULTS: Anterior leaflet geometry changed only
      slightly after chordal transection without inducing mitral regurgitation. Leaflet
      coaptation times were 79+/-17 and 87+/-22 milliseconds at the anterior
      commissure; 72+/-21, 72+/-19 milliseconds at midleaflet, and 71+/-12 and 75+/-8
      milliseconds at the posterior commissure (p = NS) for Control and Cut2,
      respectively. CONCLUSIONS: Cutting anterior second-order chordae did not cause
      delayed leaflet coaptation, alter leaflet shape, or create mitral regurgitation.
      These data indicate that transposition of second-order anterior chordae ("strut"
      chordae) is not deleterious to anterior leaflet motion per se.

PMID- 11515895
TI  - Distribution and hierarchy of regional blood flow during hypothermic
      cardiopulmonary bypass.
AB  - BACKGROUND: Cardiopulmonary bypass (CPB) may decrease oxygen delivery relative to
      the nonbypass state. We predicted that a hierarchy of regional blood flow could
      be characterized under hypothermic (27 degrees C) CPB. METHODS: Ten pigs
      underwent bypass at 27 degrees C. Fluorescent microspheres were administered
      before and during CPB at four randomized flows: 1.9, 1.6, 1.3, and 1.0 L x min(
      1) x m(-2). At completion, tissue samples were obtained from brain, renal cortex
      and medulla, pancreas, small bowel, and limb muscle for regional blood flow
      determination. RESULTS: Cerebral blood flow remained unchanged between CPB flows
      of 1.9 and 1.3 L x min(-1) x m(-2). Renal perfusion was stable between flows of
      1.9 and 1.6 L x min(-1) x m(-2), whereas perfusion of small bowel decreased
      linearly with pump flow. Pancreatic perfusion was unchanged over the range of
      flows studied; muscle blood flow was profoundly reduced at the highest CPB flow
      and further decreased if pump flow was reduced below 1.6 L x min(-1) x m(-2).
      CONCLUSIONS: This study characterizes the organ-specific hierarchy of blood flow
      and oxygen distribution during hypothermic CPB. These dynamics are relevant to
      clinical decisions for perfusion management.

PMID- 11515896
TI  - High tissue affinity angiotensin-converting enzyme inhibitors improve endothelial
      function and reduce infarct size.
AB  - BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors differ in their
      ability to inhibit tissue ACE. This study was, therefore, undertaken to determine
      whether high tissue affinity ACE inhibitors would improve endothelial function
      and thereby decrease tissue necrosis during ischemia. METHODS: In a porcine
      model, the second and third diagonal vessels were occluded for 90 minutes,
      followed by 45 minutes of cardioplegic arrest and 180 minutes of reperfusion.
      During the period of coronary occlusion, 10 pigs received enalaprilat (low
      affinity tissue ACE inhibitor), 0.05 mg/kg intravenously, 10 received quinaprilat
      (high affinity tissue ACE inhibitor), 10 mg intravenously, and 10 others received
      no ACE inhibitor. RESULTS: Wall motion scores (4, normal, to -1, dyskinesia) were
      higher in animals treated with ACE inhibitors (3.20+/-0.15 SE enalaprilat versus
      3.08+/-0.23 quinaprilat versus 1.52+/-0.07 no ACE; both p < 0.0001 from no ACE).
      Endothelial-dependent relaxation to bradykinin was best preserved in the
      quinaprilat-treated hearts (32.1%+/-7.6% enalaprilat versus 65.8%+/-12.6%
      quinaprilat versus 30.6%+/-10.7% no ACE; p < 0.0001 from no ACE; p < 0.005 from
      enalaprilat). This was associated with a greater reduction in infarct size: area
      necrosis/area risk 24.3%+/-0.8% enalaprilat (p < 0.0001 from no ACE) versus
      14.3%+/-3.2% quinaprilat (p < 0.0001 from no ACE; p < 0.005 from enalaprilat)
      versus 40.0%+/-1.7% no ACE. CONCLUSIONS: ACE inhibitors with higher affinity to
      tissue ACE result in better preservation of endothelial function and less tissue
      necrosis during coronary revascularization.

PMID- 11515897
TI  - Adenosine-enhanced ischemic preconditioning modulates necrosis and apoptosis:
      effects of stunning and ischemia-reperfusion.
AB  - BACKGROUND: Adenosine-enhanced ischemic preconditioning extends the protection of
      ischemic preconditioning by both significantly decreasing infarct size and
      significantly enhancing postischemic functional recovery. METHODS: The effects of
      adenosine-enhanced ischemic preconditioning on necrosis and apoptosis were
      investigated in the sheep heart using models of stunning (15 minutes regional
      ischemia, 120 minutes reperfusion) and ischemia-reperfusion (30 and 60 minutes
      regional ischemia, 120 minutes reperfusion). Ischemic preconditioned hearts
      received 5 minutes regional ischemia, 5 minutes reperfusion before ischemia.
      Adenosine-enhanced ischemic preconditioned hearts received a 10 mmol/L adenosine
      bolus (10 mL) through the left atrium coincident with ischemic preconditioning.
      Adenosine hearts received a 10 mmol/L bolus (10 mL) of adenosine. Regional
      ischemic hearts received no pretreatment. RESULTS: Minimal apoptosis (< 45 per
      3,000 myocytes) was observed in the stunning models but was significantly
      increased with ischemia-reperfusion in regional ischemic hearts after 30 minutes
      (p < 0.05 versus ischemic preconditioning, adenosine, or adenosine-enhanced
      ischemic preconditioning) and in adenosine and ischemic preconditioned hearts
      after 60 minutes ischemia (p < 0.05 versus adenosine-enhanced ischemic
      preconditioning). DNA laddering was apparent after 60 minutes ischemia in
      regional ischemia, adenosine, and ischemic preconditioning but not in adenosine
      enhanced ischemic preconditioned hearts. CONCLUSIONS: Adenosine-enhanced ischemic
      preconditioning significantly ameliorates necrosis and apoptosis in the regional
      ischemic blood-perfused heart.

PMID- 11515898
TI  - Endothelin receptor blockade reduces ventricular dysfunction and injury after
      reoxygenation.
AB  - BACKGROUND: Reoxygenation of hypoxic myocardium during repair of congenital heart
      defects results in poor ventricular function and cellular injury. Endothelin-1
      (ET-1), a potent vasoconstrictor that increases during hypoxia, may suppress
      myocardial function and activate leukocytes. The objective was to determine
      whether administration of an endothelin receptor antagonist could improve
      ventricular function and decrease cardiac injury after hypoxia and reoxygenation.
      METHODS: Fourteen piglets underwent 90 minutes of ventilator hypoxia, 1 hour of
      reoxygenation on cardiopulmonary bypass, and 2 hours of recovery (controls). Nine
      additional animals received an infusion of Bosentan, an ET(A/B) receptor
      antagonist, (5 mg/kg per hour) during hypoxia and reoxygenation. RESULTS: Right
      and left ventricular dP/dt in controls decreased to 78% and 52% of baseline,
      respectively, after recovery (p < 0.05). In contrast, Bosentan-treated animals
      had complete preservation of RV dP/dt and less depression of LV dP/dt. Bosentan
      reduced the hypoxia and reoxygenation-induced elevation of ET-1 and iNOS mRNA at
      the end of recovery (p < 0.05). Bosentan-treated animals had diminished
      myocardial myeloperoxidase activity and lipid peroxidation compared with controls
      (p < 0.05). Myocardial apoptotic index, elevated by hypoxia and reoxygenation,
      was lower in the Bosentan-treated animals (p < 0.05). CONCLUSIONS: Endothelin-1
      receptor antagonism improved functional recovery and decreased leukocyte-mediated
      injury after reoxygenation. The reduction in cardiac cell death might also
      improve long-term outcome after reoxygenation injury.

PMID- 11515899
TI  - Peroxynitrite formation from human myocardium after ischemia-reperfusion during
      open heart operation.
AB  - BACKGROUND: Current experimental studies have demonstrated that peroxynitrite
      (ONOO-) has both cytotoxic and cytoprotective effects on myocardial ischemia
      reperfusion injury. However, even myocardial ONOO- formation has not yet been
      investigated in humans undergoing open heart operation. We measured plasma
      nitrotyrosine as an indicator of ONOO- formation during open heart operation and
      examined its association with myocardial ischemia-reperfusion injury. METHODS:
      Twenty adult patients undergoing mitral valve replacement under cardiopulmonary
      bypass between 1997 and 1998 were enrolled in this study (6 men and 14 women).
      Arterial blood (Ao) and coronary sinus effluent (CS) were obtained: (1) before
      the initiation of cardiopulmonary bypass, (2) just after aortic unclamping, (3)
      at 5 minutes, (4) at 10 minutes, (5) at 15 minutes, and (6) at 20 minutes after
      aortic unclamping. RESULTS: At every sampling point after reperfusion, plasma
      nitrate and nitrite was significantly lower in CS than in Ao, and the percentage
      ratio of nitrotyrosine to tyrosine (%NO2-Tyr; an index of ONOO- formation) was
      significantly higher in CS than in Ao. The CS-Ao difference in %NO2-Tyr,
      myocardium-derived ONOO-, reached its peak at 5 minutes after reperfusion (2.17+/
      0.74%), which was significantly correlated with the peak CS-Ao difference in
      plasma malondialdehyde, and with postoperative maximum creatine kinase-MB.
      CONCLUSIONS: These results first demonstrate that ONOO- is produced from human
      myocardium after ischemia-reperfusion during open heart operation, and myocardium
      derived ONOO- can be determined by the CS-Ao difference in %NO2-Tyr.

PMID- 11515900
TI  - Tissue engineering: a 21st century solution to surgical reconstruction.
AB  - Tissue engineering has emerged as a rapidly expanding approach to address the
      organ shortage problem. It is an "interdisciplinary field that applies the
      principles and methods of engineering and the life sciences toward the
      development of biological substitutes that can restore, maintain, or improve
      tissue function." Much progress has been made in the tissue engineering of
      structures relevant to cardiothoracic surgery, including heart valves, blood
      vessels, myocardium, esophagus, and trachea.

PMID- 11515901
TI  - Esophageal perforation: a rare complication of Zollinger-Ellison syndrome.
AB  - Spontaneous perforation of the esophagus is a rare manifestation of Zollinger
      Ellison syndrome (ZES). Failure to recognize its existence can lead to an
      unsuccessful treatment of the esophageal perforation. We present a rare case of
      reflux esophagitis-induced esophageal perforation in a patient with ZES. Presence
      of a gastrinoma should be considered when recurrent or complicated reflux
      esophagitis is encountered.

PMID- 11515902
TI  - Minimally invasive Ivor Lewis esophagectomy.
AB  - Ivor Lewis esophagectomy consists of a laparotomy and right thoracotomy for
      resection of the intrathoracic esophagus. Recent advances in minimally invasive
      surgical technology have allowed surgeons to apply laparoscopy and thoracoscopy
      to perform esophagectomy. However, there have been few reports that describe a
      totally minimally invasive Ivor Lewis esophagectomy. We present a case of
      combined laparoscopic and thoracoscopic resection of the distal third esophagus
      with an intrathoracic esophagogastric reconstruction for esophageal carcinoma.

PMID- 11515903
TI  - Long-term survival after resection for small cell carcinoma of the esophagus.
AB  - We describe the rare case of a patient with esophageal small cell carcinoma who
      was completely cured. A 77-year-old man had small cell carcinoma of the esophagus
      with extensive lymph node metastases. Treatment comprised a subtotal
      esophagectomy and extended lymph node dissection. He has survived for more than 7
      years with no evidence of recurrent disease. We suggest that radical operations
      should be considered for future patients if curative resection can be expected.

PMID- 11515904
TI  - Glomus tumor of the trachea.
AB  - Extracutaneous glomus tumors are uncommon and rarely occur in the trachea. We
      describe a 73-year-old man with a glomus tumor of the trachea who presented with
      cough, dyspnea, chest pain, and hemoptysis. A curative segmental tracheal
      resection with primary reconstruction was performed with no recurrence at 6-year
      follow-up. The clinicopathologic features of this unusual neoplasm are discussed
      with a review of the literature.

PMID- 11515905
TI  - Operative stabilization of a flail chest six years after injury.
AB  - We report a case of operative stabilization of an incompetent upper chest wall 6
      years following flail chest. The indications for stabilization were chronic pain
      and dyspnea associated with rib malunion and loss of hemithorax volume. At
      operation, multiple pseudoarthroses were encountered and partial resection of
      ribs three and four was required. Malleable plates were used to bridge the gaps
      created by the resection and were secured in place with sternal wire. The patient
      reported a dramatic relief of symptoms and, at 18 months postoperatively,
      continues to work full-time on his cattle ranch essentially pain-free.

PMID- 11515906
TI  - Preoperative embolization in the management of a mediastinal paraganglioma.
AB  - Parangliomas are rare and highly vascular tumors of neuroendocrine cell origin
      which are treated by complete surgical resection. Preoperative embolization to
      reduce perioperative bleeding complications, although described in paragangliomas
      of the neck and carotid body, has never before been described in the case of a
      mediastinal paraganglioma. The following is a presentation of such a case of
      mediastinal paraganglioma, in which embolization was used successfully before
      surgical resection.

PMID- 11515907
TI  - Pleuropulmonary blastoma: is prophylactic resection of congenital lung cysts
      effective?
AB  - Pleuropulmonary blastomas (PPB) are rare intrathoracic tumors that can develop in
      children with preexisting pulmonary cystic lesions, inferring that the
      prophylactic resection of such cysts might prevent the onset of these malignant
      tumors. We report a patient who went on to develop PPB in the right lung despite
      having had resections for bilateral congenital pulmonary cysts 23 months earlier.
      We therefore question the effectiveness of prophylactic resection of congenital
      lung cysts on this basis.

PMID- 11515908
TI  - Herniation of the lung after video-assisted thoracic surgery.
AB  - We report a case of lung herniation occurring following video-assisted thoracic
      surgery. Although lung hernias are rare, the widespread application of video
      assisted thoracic surgery to patients at risk for lung hernia will likely result
      in more reports in the future. Consequently, pulmonologists and thoracic surgeons
      must be aware of this condition, risk factors for development, and potential
      methods of prevention in order to minimize the occurrence of this complication.

PMID- 11515909
TI  - Resuscitation in near drowning with extracorporeal membrane oxygenation.
AB  - We report a case of near drowning of a 3-year-old girl, who was admitted to our
      emergency room with a core temperature of 18.4 degrees C. After rewarming on
      cardiopulmonary bypass and restitution of her circulation, respiratory failure
      resistant to conventional respiratory therapy prohibited weaning from
      cardiopulmonary bypass. Therefore, we instituted extracorporeal membrane
      oxygenation (ECMO). Fifteen hours later, she could be weaned from ECMO but
      required assisted ventilation for another 12 days. Twenty months later there are
      no neurologic deficits.

PMID- 11515910
TI  - A spontaneous ductal aneurysm presenting with left recurrent laryngeal nerve
      palsy.
AB  - A 76-year-old man was found to have a left recurrent laryngeal nerve palsy, due
      to a spontaneous patent ductus arteriosus aneurysm. Ortner's syndrome (left
      recurrent laryngeal nerve palsy caused by cardiovascular pathology) secondary to
      patent ductus arteriosus aneurysm has not previously been described in the
      literature. We present a case, illustrated with surface rendering computer
      tomogram reconstructions.

PMID- 11515911
TI  - Computer-enhanced totally endoscopic sequential arterial coronary artery bypass.
AB  - Minimally invasive coronary artery bypass grafting of the anterior wall using a
      left anterior small thoracotomy became a routine procedure within the last 3
      years. The introduction of robotics into the cardiosurgical practice in 1998 has
      finally enabled totally endoscopic closed chest procedures. We report two
      patients with totally endoscopic left internal thoracic artery bypass grafting to
      the left anterior descending artery and the first diagonal branch in sequential
      arterial revascularization technique using the daVinci surgical system.

PMID- 11515912
TI  - Repair of coarctation in a right-sided circumflex retroesophageal aortic arch.
AB  - We describe an unusual case of a 3-month-old infant with normal cardiac situs and
      coarctation of the aorta occurring proximal to the right subclavian artery in the
      presence of a right-sided retroesophageal circumflex aortic arch and aberrant
      left subclavian artery. Preoperative evaluation with magnetic resonance imaging
      and conventional aortography led us to surgically approach this lesion through a
      right thoracotomy with a successful outcome.

PMID- 11515913
TI  - Dissection of the ascending aorta due to metastatic carcinoma.
AB  - The association of aortic dissection with a malignancy is a rare finding and
      previous reports are usually those of primary aortic sarcomas. In this report we
      present a case with typical ascending aorta dissection associated with metastatic
      carcinoma originating from the lungs. The metastatic infiltration of the
      vasovasorum of the aorta by carcinoma cells may have caused aortic dissection by
      decreasing medial strength and integrity. This is a mechanism of aortic
      dissection that we have not encountered in previous reports.

PMID- 11515914
TI  - Tricuspid dura mater bioprostheses: more than 20-year follow-up of 3 patients.
AB  - Replacement of the tricuspid valve is sometimes necessary. We report 3
      consecutive patients with tricuspid insufficiency who underwent valve replacement
      with glycerol-preserved, homologous dura mater cardiac bioprostheses between 1971
      and 1973. The first 2 patients are well 28 and 27 years later; the last patient
      was lost to follow-up after 20 years. We conclude that preservation of homologous
      dura mater bioprostheses in glycerol may reduce rates of thromboembolism,
      thrombosis, and structural dysfunction during the late postoperative period.

PMID- 11515915
TI  - Contained rupture of a myocardial abscess in the free wall of the left ventricle.
AB  - Contained rupture of the left ventricle is uncommon; rupture secondary to a
      myocardial abscess is exceedingly rare. A case is presented of a contained
      rupture of a myocardial abscess in a patient with Staphylococcus aureus
      septicemia. The rupture was repaired surgically, and the patient survived.

PMID- 11515916
TI  - Delayed presentation of right ventricular bullet embolus.
AB  - Venous bullet embolism to the heart is a rare complication of penetrating gunshot
      trauma. There are little data regarding long-term follow-up of missiles retained
      in the right ventricle. We report a rare case of right ventricular bullet embolus
      following a left-sided thoracic gunshot wound. The patient presented with delayed
      onset of cardiac irritability symptoms 4 years after injury.

PMID- 11515917
TI  - Double coronary endarterectomy on the beating heart in two patients with
      porcelain aorta.
AB  - Patients with porcelain aorta carry a high risk of systemic embolism during
      coronary artery bypass grafting. Avoiding manipulation of the aorta during
      operation using the beating heart approach can prevent atheroemboli. In patients
      with diffuse atherosclerotic coronary artery disease who require endarterectomy,
      coronary bypass operations can be done safely on the beating heart.

PMID- 11515918
TI  - Concomitant thymectomy and cardiac operation in a patient with pure red cell
      aplasia.
AB  - Pure red cell aplasia is a rare condition resulting in severe anemia. Medical
      therapy is indicated, unless a thymoma is present. In patients with concurrent
      cardiac pathology requiring operation, simultaneous operation should be
      contemplated to avoid risky resternotomy. We describe an exceptionally rare case
      of a patient with pure red cell aplasia secondary to a thymoma who underwent
      concomitant thymectomy and coronary artery grafting with a successful surgical
      outcome.

PMID- 11515919
TI  - Metastatic cardiac myxoma.
AB  - A 22-year-old woman who had a history of three cardiac operations and a bilateral
      femoral embolectomy for recurrent cardiac myxoma and myxoma embolism,
      respectively, was accepted to our clinic with multiple immobile peripheral
      masses. One of them was compressing the left common femoral artery. This mass was
      extirpated. Pathology examination revealed myxoma. Chemotherapy was given to the
      patient and regression of the masses was observed.

PMID- 11515920
TI  - Incidental malignancy in internal thoracic artery lymph nodes.
AB  - The incidental finding of malignant internal thoracic lymph nodes while
      mobilizing the internal thoracic artery (ITA) for coronary bypass grafting has
      not to our knowledge been previously reported. The cases of 3 male patients who
      underwent surgery between January 1990 and January 1993 and in whom malignant
      lymph nodes were found in the ITA pedicle are reviewed. One individual was found
      to have metastatic carcinoma of the breast, whereas the other 2 were discovered
      to have previously undiagnosed lymphomas. After undergoing further relevant
      investigation and treatment, all 3 patients remain free of recurrent disease 6.8
      to 9.8 years after their original cardiac surgery. Primary or metastatic
      malignancy may be encountered in the course of ITA mobilization for grafting.
      Abnormally enlarged internal thoracic lymph nodes should be sent for pathologic
      examination.

PMID- 11515921
TI  - Congenital quadricuspid aortic valve.

PMID- 11515922
TI  - Double transmanubrial approach and sternotomy for resection of a giant thymic
      carcinoid tumor.
AB  - The transmanubrial approach allows excellent unilateral exposure of the thoracic
      outlet. However, selected patients may require a bilateral cervicomediastinal
      exposure to completely resect the neoplasm. We report the use of a "double"
      transmanubrial approach for the resection of a giant mediastinal mass requiring
      bilateral vascular dissection and superior vena cava system resection and
      replacement.

PMID- 11515923
TI  - New technique for the cystic mediastinal tumor by video-assisted thoracoscopy.
AB  - Thoracoscopic operations for benign mediastinal tumors have been useful. However,
      it is difficult to remove cystic mediastinal tumors completely because of their
      cystic structure. We herein describe a useful technique of tumor cannulation that
      allows for the simple and safe removal of these tumors.

PMID- 11515924
TI  - Norwood-type operation with adjustable systemic-pulmonary shunt using hemostatic
      clip.
AB  - The postoperative course of a patient with hypoplastic left heart syndrome after
      a first-stage Norwood operation is governed to a large extent by the balance
      between the systemic and pulmonary circulations. Here we describe a simple and
      convenient technique for establishing an optimally sized systemic-pulmonary shunt
      by the application of a hemostatic clip. The method has been used in 6 patients.

PMID- 11515925
TI  - Extended use of radial artery with Y-graft technique for complete arterial
      revascularization.
AB  - One of the biggest problems encountered during complete arterial
      revascularization is difficulty obtaining sufficient graft length to perform
      multiple distal anastomoses. We describe a technique of dividing the radial
      artery during harvest and forming one or more composite Y-grafts to allow end-to
      side rather than sequential anastomoses without substantially decreasing usable
      conduit length. This approach has merit and may be helpful in some patients who
      require complex arterial grafting.

PMID- 11515926
TI  - Use of "BioGlue" in aortic surgical repair.
AB  - A new bioadhesive (BioGlue, Cryolife Inc, Kennesaw, GA) was recently introduced
      for surgical use in thoracic aortic surgical repair. We describe our early
      experience and our suggested method of repair.

PMID- 11515927
TI  - Lung volume reduction surgery in emphysema: a systematic review.
AB  - The aim of this study was to systematically review the literature regarding the
      safety and efficacy of lung volume reduction surgery (LVRS) in patients with
      emphysema. Studies on LVRS to August 2000 were identified using MEDLINE, Embase,
      Current Contents, and the Cochrane Library. Human studies of patients with upper,
      lower or diffuse distributions of emphysema were included. All types of bullous
      emphysema were excluded. A surgeon and researcher independently assessed the
      retrieved articles for their inclusion in the review. When LVRS was compared with
      medical management, at 2 years LVRS was associated with a higher FEV1 and at
      least equivalent survival. The use of staple excision of selected areas of lung
      appeared to be more efficacious than laser ablation. There is insufficient
      evidence to show preference for median sternotomy or videoscopically assisted
      thoracotomy, as the more safe and efficacious procedure. In highly selected
      patients with emphysema LVRS is deemed an acceptable treatment. To fully evaluate
      the safety and efficacy of LVRS, outcomes beyond 2 years must be included. The
      results of prospective randomized trials between medical management and LVRS, now
      in progress, are essential before a final assessment can be made.

PMID- 11515928
TI  - Limitations of randomized clinical trials for evaluating emerging operations: the
      case of lung volume reduction surgery.
AB  - Although unanswered questions remain, scores of observational studies and several
      small randomized clinical trials (RCTs) indicate that lung volume reduction
      surgery (LVRS) offers safe and effective palliation for a relatively well defined
      subset of patients with advanced emphysema. Nonetheless, Medicare and other
      insurers stopped reimbursement for the procedure. Subsequently, two multicenter
      RCTs on LVRS, the National Emphysema Treatment Trial (NETT) and the Overholt
      BlueCross Emphysema Surgery Trial (OBEST), were launched with the stipulation
      that the procedure would not be paid for outside these trials. Thus access to
      LVRS has been denied to patients who could benefit but do not wish to participate
      in an RCT. Emerging operations, unlike new drugs or devices, pass through
      evolutionary changes and frequently fail to produce data that meet the scientific
      rigor required by randomized studies. In such a setting, the observational
      approach is more appropriate. Indeed, almost all operations in the present
      surgical armamentarium have been evaluated and have evolved through observational
      studies without the use of RCTs. By the time new operations are standardized and
      qualify for RCTs, benefits for certain patients may be demonstrated and
      randomization could involve unacceptable health hazards. Patients from this
      population should be offered the choice between participating in RCTs and having
      the operation outside the study. Imposition of financial restrictions that bars
      access to a therapy with known benefit is a questionable practice.

PMID- 11515929
TI  - Heart transplantation.

PMID- 11515930
TI  - As originally published in 1993. Localized supravalvar aortic stenosis: a new
      technique for repair. Updated in 2001.

PMID- 11515931
TI  - Exclusion of mitral valvuloplasty from predictors of mortality for patients
      undergoing cardiac valve replacements in New York State.

PMID- 11515932
TI  - Combined transseptal superior approach to mitral valve: management of left
      superior vena cava.

PMID- 11515933
TI  - Lower sternal splitting for lateral revascularization during off-pump coronary
      artery bypass grafting using a modified "Lima" pericardial traction stitch.

PMID- 11515934
TI  - The reluctant use of femoral cannulation as a minimal access approach for
      pediatric cardiac surgery.

PMID- 11515935
TI  - S100 protein: its use as a marker of cerebral damage in cardiac operations.

PMID- 11515936
TI  - Technical notes on thoracic sympathectomy for essential hyperhidrosis.

PMID- 11515937
TI  - Intrathoracic migration of Kirschner pins: is video-assisted thoracic surgery
      justified?

PMID- 11515938
TI  - Radiation-induced secondary malignancy of the esophagus.

PMID- 11515939
TI  - Optimal filtering and Bayesian detection for friction-based diagnostics in
      machines.
AB  - Non-model-based diagnostic methods typically rely on measured signals that must
      be empirically related to process behavior or incipient faults. The difficulty in
      interpreting a signal that is indirectly related to the fundamental process
      behavior is significant. This paper presents an integrated non-model and model
      based approach to detecting when process behavior varies from a proposed model.
      The method, which is based on nonlinear filtering combined with maximum
      likelihood hypothesis testing, is applicable to dynamic systems whose
      constitutive model is well known, and whose process inputs are poorly known.
      Here, the method is applied to friction estimation and diagnosis during motion
      control in a rotating machine. A nonlinear observer estimates friction torque in
      a machine from shaft angular position measurements and the known input voltage to
      the motor. The resulting friction torque estimate can be analyzed directly for
      statistical abnormalities, or it can be directly compared to friction torque
      outputs of an applicable friction process model in order to diagnose faults or
      model variations. Nonlinear estimation of friction torque provides a variable on
      which to apply diagnostic methods that is directly related to model variations or
      faults. The method is evaluated experimentally by its ability to detect normal
      load variations in a closed-loop controlled motor driven inertia with bearing
      friction and an artificially-induced external line contact. Results show an
      ability to detect statistically significant changes in friction characteristics
      induced by normal load variations over a wide range of underlying friction
      behaviors.

PMID- 11515940
TI  - Improving performance using cascade control and a Smith predictor.
AB  - Many investigations have been done on tuning proportional-integral-derivative
      (PID) controllers in single-input single-output (SISO) systems. However, only a
      few investigations have been carried out on tuning PID controllers in cascade
      control systems. In this paper, a new approach, namely the use of a Smith
      predictor in the outer loop of a cascade control system, is investigated. The
      method can be used in temperature control problems where the secondary part of
      the process (the inner loop) may have a negligible delay while the primary loop
      (the outer loop) has a time-delay. Two different approaches, including an
      autotuning method, to find the controller parameters are proposed. It is shown by
      some examples that the proposed structure as expected can provide better
      performance than conventional cascade control, a Smith predictor scheme or single
      feedback control system.

PMID- 11515941
TI  - Robust control for a class of time varying systems via switching hypersurface
      design with output signals.
AB  - Sliding mode control methods have been used widely since they provide robustness
      against parameter variations and disturbances. This paper focuses on the problem
      of a robust output-sliding control design for linear uncertain multi-input multi
      output time-varying systems with norm-bounded uncertainty. Output signals are
      used for the definition of switching hypersurfaces. The formulation of a control
      law is emphasized. Output tracking can be achieved against a class of time
      varying parameter variations and external disturbances. The effectiveness of the
      proposed output-sliding control is confirmed by an application example.

PMID- 11515942
TI  - Comparative study of a learning fuzzy PID controller and a self-tuning
      controller.
AB  - The self-organising fuzzy controller is an extension of the rule-based fuzzy
      controller with an additional learning capability. The self-organising fuzzy
      (SOF) is used as a master controller to readjust conventional PID gains at the
      actuator level during the system operation, copying the experience of a human
      operator. The application of the self-organising fuzzy PID (SOF-PID) controller
      to a 2-link non-linear revolute-joint robot-arm is studied using path tracking
      trajectories at the setpoint. For the purpose of comparison, the same experiments
      are repeated by using the self-tuning controller subject to the same data
      supplied at the setpoint. For the path tracking experiments, the output
      trajectories of the SOF-PID controller followed the specified path closer and
      smoother than the self-tuning controller.

PMID- 11515943
TI  - A new autotuning algorithm for PID controllers using dead-beat format.
AB  - A novel algorithm for PID controllers based on dead-beat control and fuzzy
      inference mechanism is presented in this paper. The proposition is an extension
      of the work by the authors where the PI form of the algorithm was presented. The
      inclusion of the derivative term makes the method suitable for application in all
      types of processes including the ones having high rate disturbances. The proposed
      algorithm seems to be a complete and generalized PID autotuner as can be seen by
      the simulated and experimental results. In all the cases the method shows
      substantial improvement over the controller tuned with Ziegler Nichol's formula
      and the PI controller proposed in R. Bandyopadhyay, D. Patranabis, A fuzzy logic
      based PI autotuner, ISA Transactions 37 (1998) 227-235.

PMID- 11515944
TI  - Application of the SCADA system in wastewater treatment plants.
AB  - The implementation of the SCADA system has a positive impact on the operations,
      maintenance, process improvement and savings for the City of Houston's Wastewater
      Operations branch. This paper will discuss the system's evolvement, the
      external/internal architecture, and the human-machine-interface graphical design.
      Finally, it will demonstrate the system's successes in monitoring the City's
      sewage and sludge collection/distribution systems, wet-weather facilities and
      wastewater treatment plants, complying with the USEPA requirements on the
      discharge, and effectively reducing the operations and maintenance costs.

PMID- 11515945
TI  - Intelligent system for start-up of a petroleum offshore platform.
AB  - It is difficult to control and to manage the start-up of a petroleum offshore
      platform. In order to solve this problem an intelligent system can play an
      important role, since available qualitative operator and design knowledge can be
      easily implemented to assist the operator during start-up. This paper describes
      the integration of an expert system with a fuzzy controller applied to such a
      process. The intelligent system has many heuristic rules to implement the
      automation of the start-up procedures, like the opening of many on-off valves
      while simultaneously monitoring process variables. It also has a fuzzy controller
      to optimize the opening of the oil wells, in order to minimize the start-up time.
      This intelligent system is being implemented in the platform P-19 of Petrobras,
      the Brazilian oil company, in Campos Basin, Brazil. The prototype has been
      operating since October 1998.

PMID- 11515946
TI  - A framework for modelling in S88 constructs for scheduling purposes.
AB  - ISA S88.01 [1] [ISA (ANSI/S88.01.1995), Standard batch control; part 1: models
      and terminology, Instrument Society of America, 1995] is a standard that provides
      a methodology for the dissemination of a batch into standard models and provides
      the terminology for defining the control requirements of batch plants. The nature
      of S88 is such that it is not only applicable to the development of computer
      control systems for a batch plant, but also could be utilised within batch
      management software, i.e. scheduling. This paper presents a method of
      interpreting multi-purpose/product batch plant into S88 constructs to provide an
      object oriented framework for the research and development of a batch scheduling
      Matlab tool-box. Such a framework provides a thorough and efficient method of
      articulating the model to effectively apply automatic scheduling/optimisation
      methods.

PMID- 11515947
TI  - Is it malpractice for state dental boards to require competency testing on
      humans?

PMID- 11515948
TI  - Anesthetic efficacy of infiltrations in mandibular anterior teeth.
AB  - The purpose of this prospective, randomized, double-blind study was to measure
      the degree of anesthesia obtained with a labial infiltration of either 2%
      lidocaine with 1:50,000 or 2% lidocaine with 1:100,000 epinephrine in mandibular
      anterior teeth. Another objective was to measure the degree of anesthesia
      obtained with a lingual infiltration of 2% lidocaine with 1:100,000 epinephrine
      in mandibular anterior teeth. Through use of a repeated-measures design, 40
      subjects randomly received a labial infiltration at the lateral incisor apex of
      either 1.8 mL of 2% lidocaine with 1:100,000 epinephrine or 1.8 mL of 2%
      lidocaine with 1:50,000 epinephrine at 2 separate appointments. An additional 40
      subjects received a lingual infiltration at the lateral incisor apex of 1.8 mL of
      2% lidocaine with 1:100,000 epinephrine. The mandibular anterior teeth were
      blindly pulp tested at 4-minute cycles for 60 minutes postinjection. No response
      from the subject to the maximum output (80 reading) of the pulp tester was used
      as the criterion for pulpal anesthesia. Anesthesia was considered successful when
      2 consecutive 80 readings were obtained. For the 3 infiltrations, success rates
      for the lateral incisor ranged from 43 to 50%. Adjacent teeth had success rates
      of 27 to 63%. There was no significant difference (P > 0.05) in success between
      the labial infiltration of 2% lidocaine with 1:100,000 epinephrine and 2%
      lidocaine with 1:50,000 epinephrine or the lingual infiltration of 2% lidocaine
      with 1:100,000 epinephrine when compared with the labial infiltration of 2%
      lidocaine with 1:100,000 epinephrine. Duration of pulpal anesthesia declined
      steadily for all solutions over the 60 minutes. In conclusion, the success rate
      of 43-50% and declining duration of pulpal anesthesia over an hour indicates that
      a labial infiltration of 1.8 mL of either 2% lidocaine with 1:100,000 epinephrine
      or 1: 50,000 epinephrine or a lingual infiltration of 2% lidocaine with 1:100,000
      epinephrine over the lateral incisor apex cannot be recommended clinically to
      provide profound pulpal anesthesia.

PMID- 11515949
TI  - The chemical and physical stability of a 1:1 mixture of propofol and
      methohexital.
AB  - Anesthetic drugs are frequently mixed or coadministered to optimize anesthetic
      effects while minimizing adverse effects. Methohexital advantages include its low
      cost and rapid onset, while propofol provides improved airway anesthesia and
      extremely rapid clearance from the plasma. Therefore, a mixture of these agents
      might well be superior to either drug given alone. We wished to determine whether
      a mixture of methohexital and propofol is chemically and physically stable. A 1:1
      mixture of propofol 10 mg/ml and methohexital was prepared. At times varying from
      0 to 48 hours, mixtures with an internal standard of thymol kept at room
      temperature were thrice extracted with a 2:1 v/v mixture of diethyl
      ether:pentane, dried under nitrogen, and treated overnight with bis
      trimethylsilyl-trifluoroacetamide. The resultant derivatives were transferred to
      microsample vials and analyzed by GC-MS. Drug stability was quantified by
      electronic integration of peak areas representing characteristic ions for each
      drug. For each sample, the peak area of the methohexital ion (m/z 239) or
      propofol ion (m/z 235) relative to the corresponding thymol ion (m/z 207) served
      as an index of the concentration of the drug in the sample. At times varying from
      0 to 48 hours, mixtures without thymol were used to determine mean droplet size
      of the particles. This was accomplished using both an Accusizer and a Nicomp 370
      Particle Sizer. One way ANOVA tested for significant changes in drug
      concentrations and mean particle size as a function of time. There was no
      significant breakdown of propofol or methohexital when combined in a 1:1 mixture
      and allowed to stand for 48 hours, nor was there an increase in particle size
      suggestive of emulsion instability. We concluded that a 1:1 mixture of propofol
      and methohexital was stable up to 48 hours after mixing.

PMID- 11515951
TI  - The Bains of psychology.

PMID- 11515950
TI  - Propofol: a sedative-hypnotic anesthetic agent for use in ambulatory procedures.

PMID- 11515952
TI  - Footsteps and inchworms: illusions show that contrast affects apparent speed.
AB  - A horizontal grey bar that drifts horizontally across a surround of black and
      white vertical stripes appears to stop and start as it crosses each stripe. A
      dark bar appears to slow down on a black stripe, where its edges have low
      contrast, and to accelerate on a white stripe, where its edges have high
      contrast. A light-grey bar appears to slow down on a white stripe and to
      accelerate on a black stripe. If the background luminances at the leading and
      trailing edges of the moving bar are the same, the bar appears to change speed,
      and if they are different the bar appears to change in length. A plaid surround
      can induce 2-D illusions that modulate the apparent direction, not just the
      speed, of moving squares. Thus, the motion salience of a moving edge depends
      critically on its instantaneous contrast against the background.

PMID- 11515953
TI  - Identification of visual stimuli is improved by accompanying auditory stimuli:
      the role of eye movements and sound location.
AB  - Can auditory signals influence the processing of visual information? The present
      study examined the effects of simple auditory signals (clicks and noise bursts)
      whose onset was simultaneous with that of the visual target, but which provided
      no information about the target. It was found that such a signal enhances
      performance in the visual task: the accessory sound reduced response times for
      target identification with no cost to accuracy. The spatial location of the sound
      (whether central to the display or at the target location) did not modify this
      facilitation. Furthermore, the same pattern of facilitation was evident whether
      the observer fixated centrally or moved their eyes to the target. The results
      were not altered by changes in the contrast (and therefore visibility) of the
      visual stimulus or by the perceived utility of the spatial location of the sound.
      We speculate that the auditory signal may promote attentional 'disengagement' and
      that, as a result, observers are able to process the visual target sooner when
      sound accompanies the display relative to when visual information is presented
      alone.

PMID- 11515954
TI  - Is optic flow used to guide walking while wearing a displacing prism?
AB  - Rushton et al (1998 Current Biology 8 1191 - 1194) recently showed that walkers
      wearing displacing prisms follow curved trajectories determined by the perceived
      direction of their target. This suggests that optic flow is not important in
      guidance, since flow cues are unaffected by the prism and should allow a
      straight, direct trajectory. We replicated Rushton et al's result but also tried
      to rule out an important artifact associated with the prism. Prisms restrict the
      field of view and, particularly, access to the foreground optic flow that is
      likely to be important in providing guidance cues. We found that performance did
      not improve when walkers directed their gaze to include the foreground flow,
      suggesting that Rushton et al's results were not due to this artifact. On the
      other hand, performance did reliably improve when subjects reduced their viewing
      height by crawling towards the target. This improvement may be due to coarsening
      of the visual texture or to increased salience of alignment and motion-parallax
      cues. Whatever its cause, the improvement demonstrates that guidance is not
      determined only by perceived target direction and that, under some conditions,
      flow may be important.

PMID- 11515955
TI  - The perception of texture on folded surfaces.
AB  - Do judgments of texture similarity reflect surface texture or image texture? To
      find out, we had observers view a rectangular surface that was folded into three
      panels, much like a brochure. Each panel was textured with an oriented noise
      pattern and the observers' task was to determine which side panel matched the
      center panel in surface texture. Information about surface geometry was conveyed
      by binocular disparity and by the boundaries of the rectangular surface. We found
      that observers were often consistently wrong, selecting the texture that differed
      in the image and not on the surface. In sharp contrast, when observers judged the
      texture orientation on each panel individually, their judgments were accurate
      reflections of the surface texture. So even when observers can recover surface
      texture, their judgments of texture similarity may still be based on image
      texture.

PMID- 11515956
TI  - Processing time of contour integration: the role of colour, contrast, and
      curvature.
AB  - We investigated the temporal properties of the red - green, blue-yellow, and
      luminance mechanisms in a contour-integration task which required the linking of
      orientation across space to detect a 'path'. Reaction times were obtained for
      simple detection of the stimulus regardless of the presence of a path, and for
      path detection measured by a yes/no procedure with path and no-path stimuli
      randomly presented. Additional processing times for contour integration were
      calculated as the difference between reaction times for simple stimulus detection
      and path detection, and were measured as a function of stimulus contrast for
      straight and curved paths. We found that processing time shows effects not
      apparent in choice reaction-time measurements. (i) Processing time for curved
      paths is longer than for straight paths. (ii) For straight paths, the achromatic
      mechanism is faster than the two chromatic ones, with no difference between the
      red-green and blue-yellow mechanisms. For curved paths there is no difference in
      processing time between mechanisms. (iii) The extra processing time required to
      detect curved compared to straight paths is longest for the achromatic mechanism,
      and similar for the red - green and blue-yellow mechanisms. (iv) Detection of the
      absence of a path requires at least 50 ms of additional time independently of
      chromaticity, contrast, and path curvature. The significance of these differences
      and similarities between postreceptoral mechanisms is discussed.

PMID- 11515957
TI  - Visual inter-attribute contour completion.
AB  - A new visual phenomenon, inter-attribute illusory (completed) contours, is
      demonstrated. Contour completions are perceived between any combination of
      spatially separate pairs of inducing elements (Kanizsa-like 'pacman' figures)
      defined either by pictorial cues (luminance contrast or offset gratings),
      temporal contrast (motion, second-order-motion or 'phantom' contours), or
      binocular-disparity contrast. In a first experiment, observers reported the
      perceived occurrence of contour completion for all pair combinations of inducing
      elements. In a second experiment they rated the perceived clarity of the
      completed contours. Both methods generated similar results contour completions
      were perceived even though the inducing elements were defined by different
      attributes. Ratings of inter-attribute clarity were no lower than in either of
      the two corresponding intra-attribute conditions and seem to be the average of
      these two ratings. The results provide evidence for the existence of attribute
      invariant Gestalt processes, and on a mechanistic level indicate that the
      completion process operates on attribute-invariant contour detectors.

PMID- 11515958
TI  - Connectivity perception of partly occluded gratings in 4-month-old infants.
AB  - Four groups of eight 4-month-old infants were each habituated to one of four
      displays consisting of a grating of either low (0.4 cycle deg(-1) or high (1.2
      cycles deg(-1) spatial frequency, whose central portion was covered up with a
      horizontal occluder which was either narrow (1.33 deg) or broad (4.17 deg).
      Posthabituation displays consisted of a complete grating of the same frequency as
      the habituated grating, along with a separate grating whose central portion was
      replaced with a black gap of the same height as the occluder in the habituation
      displays. All the infants, except those who were habituated to the high frequency
      with the broad occluder, looked longer at the separate grating than the complete
      grating display during posthabituation trials. Previously, we found that infants
      under 1 month of age perceive the grating continuation only when the occluder
      height is less than about 0.5 cycle of the grating; our present results show that
      this figure increases to about 1.6 cycles of the grating frequency in the case of
      4-month-old infants. These findings indicate that those developmental changes
      depend on both the sufficiency of visual information available and the efficiency
      of the perceptual ability of infants for grasping spatial relationships.

PMID- 11515959
TI  - Dynamic properties influence the perception of facial expressions.
AB  - Two experiments were conducted to investigate the role played by dynamic
      information in identifying facial expressions of emotion. Dynamic expression
      sequences were created by generating and displaying morph sequences which changed
      the face from neutral to a peak expression in different numbers of intervening
      intermediate stages, to create fast (6 frames), medium (26 frames), and slow (101
      frames) sequences. In experiment 1, participants were asked to describe what the
      person shown in each sequence was feeling. Sadness was more accurately identified
      when slow sequences were shown. Happiness, and to some extent surprise, was
      better from faster sequences, while anger was most accurately detected from the
      sequences of medium pace. In experiment 2 we used an intensity-rating task and
      static images as well as dynamic ones to examine whether effects were due to
      total time of the displays or to the speed of sequence. Accuracies of expression
      judgments were derived from the rated intensities and the results were similar to
      those of experiment 1 for angry and sad expressions (surprised and happy were
      close to ceiling). Moreover, the effect of display time was found only for
      dynamic expressions and not for static ones, suggesting that it was speed, not
      time, which was responsible for these effects. These results suggest that
      representations of basic expressions of emotion encode information about dynamic
      as well as static properties.

PMID- 11515960
TI  - Simultaneous lightness contrast with double increments.
AB  - In this paper we demonstrate the existence of simultaneous lightness contrast in
      displays in which the target patches are both more luminant than their surrounds.
      These effects are not predicted by theories of lightness that assume that the
      highest luminance in a scene is perceived as white, and anchors all the other
      luminances. We show that the strength of double-increment illusions depends
      crucially on the luminance of both the surrounds and the target patches. Such
      luminance prerequisites were not met in previous studies, which explains why
      simultaneous contrast with incremental targets has so far been regarded as
      extremely weak or nonexistent.

PMID- 11515961
TI  - Novel techniques to establish new insect cell lines.
AB  - The success of insect cell culture is demonstrated by reports of over 500
      established cell lines. While established procedures that can be used for
      developing new cell lines exist, these usually require some fine-tuning for
      various tissue sources. This paper attempts to depict some of the variations that
      can be applied.

PMID- 11515962
TI  - Hemolymph analysis and evaluation of newly formulated media for culture of shrimp
      cells (Penaeus stylirostris).
AB  - Creation of a shrimp cell line has been an elusive goal. This failure may be due
      to the composition of the cell culture medium, which may be inadequate to support
      primary cultured cells. Shrimp hemolymph should contain the nutritional
      components needed to support cell growth and division. We report here the
      comprehensive biochemical analysis of hemolymph from the blue shrimp, Penaeus
      stylirostris (Litopenaeus stylirostris) (see Holthuis, L. B. Shrimps and prawns
      of the world, in: FAO species catalog. Vol. 1. Rome: Food and Agriculture
      Organization of the United Nations; 1980), for free amino acids (FAAs),
      carbohydrates, electrolytes, metals, pH, and osmolality. Levels of hemolymph
      components were compared to 2xL-15 with 20% fetal bovine serum, a commonly used
      culture medium for crustacean cells. The FAAs, taurine and proline, and the
      metals, strontium and zinc, were significantly higher in hemolymph than in the 2
      x L-15 medium. In contrast, other FAAs were up to 50 times higher in the 2 x L-15
      medium than in the hemolymph. To mimic more closely the hemolymph composition, we
      created two new media based on either the 0.2 x L-15 or the M199 medium. We
      compared the microscopic appearance of cells cultured in these media and
      evaluated deoxyribonucleic acid (DNA) and protein synthesis by 3H-thymidine
      uptake and 35S-methionine uptake assays. The ovary cells of P. stylirostris
      cultured in either of the new media formed monolayers, while the cells cultured
      in 2 x L-15 medium did not. Despite these differences, there was no evidence of
      sustained DNA or protein synthesis with any of the media. Future studies to
      establish a shrimp cell line should focus on analysis of the cell cycle and on
      overcoming the molecular blocks to cell division.

PMID- 11515963
TI  - Development of highly nutritive culture media.
AB  - A highly nutritive culture medium (MGM-464) was developed for insect cell primary
      culture. The new medium consists of 6 inorganic salts, 4 organic acids, 21 amino
      acids, 3 sugars, 10 vitamins, and 8 other chemicals, including natural
      substances. The complete medium was generated by adding 20 ml fetal bovine serum
      to 100 ml MGM-464. The detail of the composition of the medium is given in a
      table, and the protocol to prepare the medium is described in the text. Among the
      15 kinds of cultures made with MGM-464, embryonic cells from a walking stick and
      ovarian cells from the common white were subcultured more than 70 times, and
      embryonic cells of a chrysomelid beetle were subcultured more than 15 times.
      Other cultures could not be subcultured. However, embryonic cells from the
      commercial silkworm and a cockroach, ovarial cells from the commercial silkworm
      and a sphingid moth, nervous cells from the commercial silkworm and two sphingid
      moths, and cells from the dorsal vessel plus surrounding tissue of the commercial
      silkworm survived for several mo. The cells from the honeybee embryos, aphid
      embryos, and planthopper embryos were rather short-lived, and deteriorated after
      about 1 mo.

PMID- 11515964
TI  - The role of stem cells in midgut growth and regeneration.
AB  - The Manduca sexta (L.) [Lepidoptera: Sphingidae] and Heliothis virescens (F.)
      [Lepidoptera: Noctuidae] midguts consist of a pseudostratified epithelium
      surrounded by striated muscle and tracheae. This epithelium contains goblet,
      columnar, and basal stem cells. The stem cells are critically important in that
      they are capable of massive proliferation and differentiation. This growth
      results in a fourfold enlargement of the midgut at each larval molt. The stem
      cells are also responsible for limited cell replacement during repair. While the
      characteristics of the stem cell population vary over the course of an instar,
      stem cells collected early in an instar and those collected late can start in
      vitro cultures. Cultures of larval stem, goblet, and columnar cells survive in
      vitro for several mo through proliferation and differentiation of the stem cells.
      One of the two polypeptide differentiation factors which have been identified and
      characterized from the culture medium has now been shown to be present in midgut
      in vivo. Thus the ability to examine lepidopteran midgut stem cell growth in
      vitro and in vivo is proving to be effective in determining the basic features of
      stem cell action and regulation.

PMID- 11515965
TI  - Cockroach midgut peptides that regulate cell proliferation, differentiation, and
      death in vitro.
AB  - The number of insect midgut cells is maintained homeostatically in vivo and in
      vitro. However, during starvation, the midgut shrinks and the rate of cell
      replacement appears to be suppressed. When they undergo metamorphosis, the
      internal organs of insects are drastically remodeled by cell proliferation,
      differentiation, and apoptotic processes, and the net number of cells usually
      increases. An extract of 1650 midguts of Periplaneta americana was fractionated
      by high-performance liquid chromatography (HPLC) to obtain the peptides that
      regulate these processes. The HPLC fractions were tested for myotropic activity
      in the foregut and for effects on cell proliferation or loss in primary cultures
      of larval Heliothis virescens midgut cells and in a cell line derived from the
      last-instar larval fat body of Mamestra brassicae. Some fractions stimulated
      midgut stem cell proliferation and differentiation, while others caused loss of
      differentiated columnar and goblet cells. Other fractions stimulated cell
      proliferation in the larval fat body cells.

PMID- 11515966
TI  - Control of life, death, and differentiation in cultured midgut cells of the
      lepidopteran, Heliothis virescens.
AB  - Differentiated cells in the insect midgut depend on stem cells for renewal. We
      have immunologically identified Integrin beta1, a promotor of cell-cell adhesion
      that also induces signals mediating proliferation, differentiation, and apoptosis
      on the surfaces of cultured Heliothis virescens midgut cells; clusters of
      immunostained integrin beta1-like material, indicative of activated integrin,
      were detected on aggregating midgut columnar cells. Growth factor-like peptides
      (midgut differentiation factors 1 and 2 [MDF1 and MDF2]), isolated from
      conditioned medium containing Manduca sexta midgut cells, may be representative
      of endogenous midgut signaling molecules. Exposing the cultured midgut cells to
      Bacillus thuringiensis (Bt) toxin caused large numbers of mature differentiated
      cells to die, but the massive cell death simultaneously induced a 150-200%
      increase in the numbers of midgut stem and differentiating cells. However, after
      the toxin was washed out, the proportions of cell types returned to near-control
      levels within 2 d, indicating endogenous control of cell-population dynamics.
      MDF1 was detected immunologically in larger numbers of Bt-treated columnar cells
      than controls, confirming its role in inducing the differentiation of rapidly
      produced stem cells. However, other insect midgut factors regulating increased
      proliferation, differentiation, as well as inhibition of proliferation and
      adjustment of the ratio of cell types, remain to be discovered.

PMID- 11515967
TI  - Primary and continuous midgut cell cultures from Pseudaletia unipuncta
      (Lepidoptera: Noctuidae).
AB  - Midgut epithelial cells were isolated from fifth-instar Pseudaletia unipuncta
      larvae by collagenase treatment of midgut tissue, and cultured in TNM-FH medium.
      Long-term continuous culture and maintenance of midgut cells were achieved with
      P. unipuncta armyworm intestinal cells. Several cells lines were obtained from
      these P. unipuncta primary cultures, and they have been subcultured and
      maintained for over 24 mo. The three major midgut cell types were present in the
      cultures, including stem (regenerative), columnar, and goblet cells. In vitro
      morphogenesis and differentiation of columnar and goblet cells from stem cells
      were observed. There appeared to be a cycle of cell death of goblet and columnar
      cells followed by their replacement from stem cells every 7-8 wk. After
      approximately six passages, the cell density in T-flasks appeared to be somewhat
      constant, reaching 10(3)-10(4) cells per milliliter of medium. The columnar cells
      are round to rectangular in shape and possess a brush border, while the goblet
      cells have a classic flask-like shape with a central cavity. Peritrophic membrane
      like secretions were observed in all the culture flasks. Infection of these cells
      with multiply embedded nucleopolyhedrovirus was confirmed, and we conclude that
      these midgut cells can be used as an in vitro model system to study early events
      in baculovirus infection.

PMID- 11515968
TI  - A novel method for implantation of LNCaP prostate tumor cells under the renal
      capsule.

PMID- 11515969
TI  - A simple organ culture system for human fetal skin reveals that there are two
      phases in the melanocyte maturation in the dermis.

PMID- 11515970
TI  - Establishment and characterization of insect cell lines from 10 lepidopteran
      species.
AB  - Cell lines from selected lepidopteran species were established for the overall
      purpose of use in baculovirus production. A total of 36 new cell lines from 10
      lepidopteran species were generated, including cell lines from a pyralid, the
      European corn borer, Ostrinia nubilalis, a plutellid, the diamondback moth,
      Plutella xylostella, as well as eight noctuids: the black cutworm, Agrotis
      ipsilon, the celery looper, Anagrapha falcifera, the velvetbean caterpillar,
      Anticarsia gemmatalis, the corn earworm, Helicoverpa zea, the tobacco budworm,
      Heliothis virescens, the beet armyworm, Spodoptera exigua, the fall armyworm,
      Spodoptera frugiperda, and the cabbage looper, Trichoplusia ni. Tissues used for
      cell line establishment included fat bodies, ovaries, testes, or whole
      embryos/larvae/pupae. All the cell lines were subcultured numerous times,
      characterized by isoenzyme analysis and/or deoxyribonucleic acid amplification
      fingerprinting using polymerase chain reaction, and stored in liquid nitrogen.
      Many of the cell lines were adapted to grow in serum-free medium, with cell lines
      from A. ipsilon and H. virescens being adapted to suspension culture using shaker
      flasks. The potential use for these cell lines in baculovirus production is
      discussed.

PMID- 11515971
TI  - Production of selected baculoviruses in newly established lepidopteran cell
      lines.
AB  - One key to the in vitro mass production of baculoviruses is the development of
      insect cell lines capable of producing high levels of extracellular virus (ECV)
      and/or occlusion bodies (OBs). For this study, 34 newly established cell lines
      from 10 lepidopteran species were screened for their ability to produce ECV and
      OBs from a variety of baculoviruses. The selected baculoviruses included: the
      alfalfa looper virus (AcMNPV); the celery looper virus (AfMNPV); the velvetbean
      caterpillar virus (AgMNPV), the bollworm virus (HzSNPV), the diamondback moth
      virus (PxMNPV), and the beet armyworm virus (SeMNPV). ECV titers were determined
      using TCID50 assays (50% tissue culture infectivity dose), with the presence or
      absence of OBs being noted. For AcMNPV, 28 new cell lines were tested, with eight
      producing AcMNPV ECV titers of 1.1-47.3 x 10(6) TCID50/ml and 11 producing OBs.
      For AgMNPV, six new cell lines were tested, with all producing AgMNPV ECV titers
      of 3.5-62.3 x 10(6) TCID50/ml and generating OBs. For HzSNPV, four new cell lines
      were tested with three lines producing HzSNPV ECV titers of 1.4-5.0 x 10(6)
      TCID50/ml, but none generating OBs. For PxMNPV, 10 new cell lines were tested
      with seven generating PxMNPV ECV titers of 4.7-232.6 x 10(6) TCID50/ml and eight
      producing OBs. Lastly, using qualitative or semiquantitative methods, homologous
      cell lines were tested for AfMNPV and SeMNPV production, all of which produced
      OBs. Overall, many of the cell lines tested were found to produce OBs and
      generate moderate to high levels of ECVs of one or more baculoviruses.

PMID- 11515972
TI  - Optimization of culture conditions for determining hepatobiliary disposition of
      taurocholate in sandwich-cultured rat hepatocytes.
AB  - This study was undertaken to examine the influence of time and volume of collagen
      overlay, type of media, and media additives on taurocholate (TC) accumulation and
      biliary excretion in hepatocytes cultured in a collagen-sandwich configuration.
      Hepatocytes were isolated from male Wistar rats by in situ perfusion with
      collagenase, seeded onto collagen-coated 60-mm dishes, overlaid with gelled
      collagen, and cultured for 4 d. Experiments to examine the influence of time and
      volume of collagen overlay were conducted in Dulbecco's modified Eagle's medium
      (DMEM) + 1.0 microM dexamethasone (DEX) + 5% fetal bovine serum (FBS).
      Hepatocytes were overlaid at 0 h with 0.1 or 0.2 ml collagen, or at 24 h with 0.1
      or 0.2 ml collagen. The influence of media type and additives was examined in
      hepatocytes overlaid at 0 h with 0.2 ml collagen and incubated in DMEM + 0.1
      microM DEX, DMEM +/- 0.1 microM DEX + 5% FBS, Williams' medium E + 0.1 microM DEX
      + 1% ITS+, DMEM + 1.0 microM DEX, DMEM + 1.0 microM DEX + 5% FBS, or modified
      Chee's medium (MCM) + 0.1 microM DEX + 1% ITS+. [3H] TC accumulation by
      hepatocytes in Hank's balanced salt solution (HBSS) and Ca2+-free HBSS was
      measured, and the biliary-exeretion index (BEI: percentage of accumulated TC
      localized in the canalicular compartment) was calculated. Light microscopy and
      carboxydichlorofluorescein fluorescence were employed to examine the cellular and
      canalicular morphologies. The volume of collagen used for both the substratum and
      the overlay did not affect TC accumulation or biliary excretion. The BEI tended
      to be higher in cells overlaid at 24 h (BEI = 0.649 [0.1 ml collagen]; BEI =
      0.659 [0.2 ml collagen]) compared with those overlaid at 0 h after seeding (BEI =
      0.538 [0.1 ml collagen]; BEI = 0.517 [0.2 ml collagen]), although the differences
      were not statistically significant. Hepatocytes cultured in MCM produced
      consistently the lowest BEI of TC (BEI = 0.396). Differing DEX concentrations
      (0.1 microM versus 1.0 microM) with or without 5% FBS did not appear to have a
      significant effect on the BEI of TC.

PMID- 11515973
TI  - Characterization of kidney epithelial cells from the Florida manatee, Trichechus
      manatus latirostris.
AB  - The West-Indian manatee, Trichechus manatus latirostris, is a herbivorous marine
      mammal found in the coastal waters of Florida. Because of their endangered
      status, animal experimentation is not allowed. Therefore, a cell line was
      developed and characterized from tissue collected during necropsies of the
      manatees. A primary cell culture was established by isolating single cells from
      kidney tissue using both enzymatic and mechanical techniques. Primary manatee
      kidney (MK) cells were subcultured for characterization. These cells were
      morphologically similar to the cell lines of epithelial origin. An
      immunocytochemistry assay was used to localize the cytokeratin filaments common
      to cells of epithelial origin. At second passage, epithelial-like cells had an
      average population-doubling time of 48 h, had an optimum seeding density of 5 x
      10(3) cells/cm2, and readily attached to plastic culture plates with a high level
      of seeding efficiency. Although the epithelial-like cells had a rapid growth rate
      during the first three passages, the cloning potential was low. These cells did
      not form colonies in agar medium, were serum dependent, had a limited life span
      of approximately nine passages, and possessed cell-contact inhibition. These data
      suggest that the cells were finite (noncontinuous growth), did not possess
      transformed properties, and were of epithelial origin. These cells are now
      referred to as MK epithelial cells.

PMID- 11515974
TI  - Features of asthma in the elderly.
AB  - Asthma has been considered a rare disease in the elderly, but recent studies have
      shown that it is as common in the elderly as in the middle-aged population.
      Diagnosis of asthma is often overlooked in older patients, leading to
      undertreatment. Spirometry, determination of expiratory flow lability, and
      histamine challenge tests are tools that are as usefulfor the evaluation of
      elderly asthmatics as they areforyoungerpatients. Asthma is more severe in the
      elderly, especially in long-standing asthmatics. Treatment of asthma in the
      elderly should follow the same stepwise guidelines that are recommended for all
      age groups, though it will require more intense monitoring. An aggressive
      treatment approach to mild and moderate asthma in young people is the best hope
      of changing the future trends of asthma in the elderly.

PMID- 11515975
TI  - Serum specific IgE reactivity to recombinant Der f 11 in asthmatic children.
AB  - This study was designed to examine the prevalence of positive serum IgE
      reactivity to the recombinant group 11 Dermatophagoides farinae allergen (rDer f
      11) in asthmatic children in Taiwan. Using immunoblot analysis in a preliminary
      study of 18 asthmatic children, 13 (72.2%) reacted positively to rDer f 11 and 16
      (88.9%) showed positive reactivity to D. farinae extracts. The allergenicity of
      rDer f 11 was further evaluated with in vivo skin tests and in vitro IgE
      immunodot assays in 24 mite skin-test-positive asthmatic children. Whereas 17
      (70.8%) had positive skin tests to rDer f 11, 18 (75.0%) had positive serum IgE
      reactivity to rDer f 11. A good coincidence (87.5%) between the immunodot assay
      and the skin test was confirmed in these asthmatic children. Moreover, the
      prevalence of serum IgE reactivity to rDer f 11 was further investigated in a
      large panel of 49 mite skin-test-positive asthmatic children. Again, 38 (77.6%)
      had positive serum IgE reactivity to rDer f 11 in immunodot assays. Taken
      together the positive IgE reactivity to rDer f 11 in immunodot analysis ranged
      from 75 to 77.6% in two groups of 73 mite skin-test-positive asthmatic children.
      High incidence of serum IgE antibodies specific for rDer f 11 in the present
      study suggests that Der f 11 is a novel major allergen of house dust mites.

PMID- 11515976
TI  - When air is rare: behind the scenes of an asthma web site.
AB  - OBJECTIVE: The number of medical Web sites has increased tremendously during the
      past 5 years. While the quality of the content has also been on the rise, some
      questions are still open: Where are users referredfrom, how large is the target
      audience, and how do they behave during their visit? METHODS: The Asthma
      Information Center is an independent Web site for physicians, patients, and other
      health care professionals providing information about asthma. Besides mirroring
      electronic documents of the Global InitiativeforAsthma, numerous interactive
      pages have been constructed. MAIN OUTCOME MEASURES: Logfiles of the Web server
      were analyzed for a 5-year interval for numbers of page views, visitors, visits,
      and external referring sites. RESULTS: The number of visitors has increased since
      1995, up to 100,000 page views at the end of the observation interval. In
      February 2000 approximately 9000 visitors were recorded per month. 3.4 pages were
      retrieved per visit, which lasted on average 1:57 min. Users are referred
      primarily by portal sites and only to a lesser extent by search engines.
      CONCLUSIONS: The audience is large for a specialized medical Web site. Users are
      usually referred from nonmedical sites. They are seeking fast information, most
      probably as a second opinion after having consulted their physician.

PMID- 11515977
TI  - Improvement in health care utilization and pulmonary function with fluticasone
      propionate in patients with steroid-dependent asthma at a National Asthma
      Referral Center.
AB  - The impact of switching from other inhaled corticosteroids to fluticasone
      propionate was studied in patients with severe oral-steroid-dependent asthma over
      a 1-year period. In this open-label prospective study, patients on maintenance
      doses of oral and inhaled steroids were referred to a national asthma treatment
      center and were switchedfrom their previous inhaled corticosteroid to fluticasone
      propionate 880 microg BID. Compared with data collected from the year prior to
      enrollment, treatment with fluticasone propionate resulted in significant
      improvements in pulmonary function, oral steroid requirements, and health
      resource utilization. In addition, five patients were completely weaned off oral
      steroids.

PMID- 11515978
TI  - Low-attenuation areas of the lungs on high-resolution computed tomography in
      asthma.
AB  - To investigate the low-attenuation areas of the lungs (LAA) in asthma, we
      compared the mean lung density (MLD) and the LAA in 22 asthmatics (12 ex-smokers
      and 10 nonsmokers) and 13 patients with chronic obstructive pulmonary disease
      (COPD) by high-resolution computed tomography. The MLD and the relative area of
      the lung with attenuation values lower than -950 Hounsfield Units at full
      inspiration (inspiratory RA950) were significantly different in nonsmoking
      asthmatics compared to patients with COPD and asthmatics with a smoking history.
      The MLD and the RA950 correlated significantly with the FEV1 in all groups and
      with the DL(CO) in patients with COPD and asthmatics with a smoking history but
      not in nonsmoking asthmatics. We concluded that the LAA in asthmatics with a
      smoking history indicates the presence of emphysema, but in nonsmoking asthmatics
      it reflects hyperinflation and nonemphysematous expiratory airflow limitation
      rather than emphysematous lesions.

PMID- 11515979
TI  - The effect of wearing the veil by Saudi ladies on the occurrence of respiratory
      diseases.
AB  - It is customary in clinical practice and elsewhere to put on a mask for
      protection against infection, dust, and so forth. The veil, which is
      traditionally worn by women in many Muslim countries, especially in Saudi Arabia,
      may have a similar effect. The study was carried out during 1998-1999 in the
      eastern province of Saudi Arabia. Adult women were asked to answer a structured
      questionnaire related to the occurrence of respiratory tract problems and about
      veil wearing. Veil wearing was practiced by 58% of the sample. Respiratory
      infections and asthma were significantly more common in veils users (p < 0.00001
      and p < 0.0003, respectively). This unexpected finding was probably secondary to
      infection. More and bigger studies are recommended.

PMID- 11515980
TI  - Beliefs that support the behavior of people with asthma: a qualitative
      investigation.
AB  - Differences between patients' knowledge and behavior in relation to asthma may
      account for continuing morbidity in theface of professional and public asthma
      education campaigns. We conducted a qualitative study of beliefs that support
      asthma-related behavior, obtaining data from interviews with 70 adult patients.
      Analysis identified four clear subgroups, or "streams," of adults with asthma: an
      "anonymous" stream, who doubt that they have asthma and manage symptoms outside
      the organized health system; an "isolated" stream, who feel dependent on
      bronchodilators and do not understand the potential of preventive therapy; a
      "suboptimal" stream, who are confident that they are managing their asthma
      effectively but who are excessively reliant on bronchodilators; and an "optimal
      stream," who have high expectations of outcomes and participate actively in a
      partnership with a doctor. Characteristics of the doctor and the doctor-patient
      relationship are important elements in altering asthma-related behavior in ways
      that may facilitate the best health outcomes.

PMID- 11515981
TI  - Mechanical fluid flow enhances high-affinity-IgE-receptor-mediated secretion by
      mast cells adherent to fibronectin.
AB  - We demonstrated the effect of interaction between mechanical fluid flow and the
      extracellular matrix on high-affinity-IgE-receptor (FcepsilonRI)-mediated
      secretion by mast cells (cell line MC/9). Mechanical fluid flow did not affect
      secretion by the cells in the absence of exogenou agonists. Mechanical fluid flow
      did not affect secretion by cells adherent tofibronectin in the absence of
      exogenous agonists, but it did enhance FcepsilonRI-mediated secretion by cells
      adherent tofibronectin. These finding indicate that fluid-flow-induced
      enhancement of secretion by mast cells requires both exogenous agonists and
      interaction between integrins and the extracellular matrix. The present study is
      thefirst to demonstrate that mechanical fluid flow enhances FcepsilonRI-mediated
      secretion by a mast cell line adherent tofibronectin.

PMID- 11515982
TI  - Lower extremity blood flow in healthy men: effect of smoking, cholesterol, and
      physical activity--a Doppler study.
AB  - Tobacco smoking is one of the principal risk factors of peripheral arterial
      disease (PAD); cholesterol level has a lesser impact. The effect of leisure-time
      physical activity (LTPA) has not been studied in depth. The aim of this study was
      to determine the relative effects of smoking, total cholesterol, and leisure-time
      physical activity on blood flow parameters in the lower extremities of healthy
      middle-aged men with no prior symptoms or diagnosis of PAD. The authors examined
      130 men, aged 40-65 years, free of known arterial disease and hypertension. The
      men had either a total cholesterol concentration of < 5.7 or > 7.0 mmol/L, and
      were either smokers or nonsmokers. LTPA was addressed by a questionnaire. Ankle
      brachial index (ABI) was calculated and Doppler examination of the femoral artery
      was performed before and after an exercise test. Tobacco smoking related
      significantly to abnormal ABI and Doppler results (odds ratio [OR] 2.42) while
      the total cholesterol level did not. LTPA had a favorable effect (OR 0.51).
      Abnormal ABI response was greatest in smokers with high total cholesterol (p <
      0.01). Tobacco smoking is a significant risk factor for abnormal ABI response and
      blood flow abnormalities in healthy men. Regular physical activity has a
      measurable protective effect. An abnormal ABI suggests early atherosclerosis and
      indicates risk factor assessment and physician intervention.

PMID- 11515983
TI  - Association of left ventricular hypertrophy and aortic dilation in patients with
      acute thoracic aortic dissection.
AB  - This study was designed to evaluate the impact of left ventricular mass on aortic
      diameters in patients who presented with acute thoracic aortic dissection where
      aortic dilation is common. Retrospective review of transthoracic and
      transesophageal echocardiograms was conducted for 63 patients treated for acute
      thoracic aortic dissection and for 16 normal subjects who were comparable for
      gender prevalence, age, heart rate, and blood pressure. The diameter of the
      aortic root was measured by transthoracic echocardiography. Diameters of the
      ascending aorta, and of the aorta at locations of 25, 30, and 35 cm from the
      dental arch were measured by transesophageal echocardiography. The findings
      indicated that all aortic diameters were significantly larger in patients with
      aortic dissection. Patients with aortic dissection also presented with greater
      left ventricular mass indices (p<0.00001) than normal subjects. Fractional
      shortening and left atrial diameter measurements obtained in patients with aortic
      dissection were similar to those obtained in the control group. Overall, the left
      ventricular mass index exhibited univariate relationships with aortic root
      diameter (r=0.27, p<0.02) and aortic diameters at 25 cm (r=0.51, p<0.00001), 30
      cm (r=0.58, p<0.00001), and 35 cm (r=0.55, p<0.00001) distal to the arch but not
      with the diameter of the ascending aorta. After adjusting for gender, body mass
      index, history of hypertension and aortic dissection extent (Stanford types) by
      separate multivariate models, the authors found that the left ventricular mass
      index was independently associated with aortic diameters at 25 cm (beta=0.32,
      p<0.001), 30 cm (beta=0.38, p<0.0001), and 35 cm (beta=0.34, p < 0.0005) distal
      to the arch. They conclude that left ventricular mass is independently associated
      with aortic arch and descending aorta diameters in patients with acute thoracic
      aortic dissection. Left ventricular hypertrophy may be considered a risk factor
      for aortic enlargement and subsequent dissection.

PMID- 11515984
TI  - Clinical characteristics influence aortic root dimension and blood flow velocity
      in healthy subjects.
AB  - The aim of this study was to determine if aortic root dimension and blood flow
      velocity correlate with clinical and echocardiographic characteristics of healthy
      individuals. To assess the aortic root dimension and blood flow velocity in a
      healthy population, 503 subjects (253 women and 250 men) aged 18 to 66 years
      (mean, 36.9+/-11.9 years) who were normotensive, free of clinically apparent
      heart disease and any drug at the baseline examination were included in the
      study. M-mode echocardiographic measurements were performed according to the
      criteria recommended by the American Society of Echocardiography. Aortic blood
      velocity was obtained by pulsed wave Doppler echocardiography. Correlations
      between aortic root dimension and blood flow velocity and age, gender, body
      surface area, waist/hip ratio, and echocardiographic parameters such as left
      ventricular mass, ejection fraction, and left ventricular systolic and diastolic
      dimensions were evaluated by using regression analysis and Student's t test. Men
      had greater aortic root dimension (p<0.001). There were correlations between
      aortic root dimensions and age, body surface area, waist/hip ratio, and left
      ventricular mass in both genders (p<0.05). No correlation was found with left
      ventricular dimensions and ejection fraction. Aortic blood flow velocity
      correlated only with age (r=0.32, p<0.001). There was no gender difference in
      aortic blood flow velocity. This study shows that age, gender, body surface area,
      and waist/hip ratio should be considered in the evaluation of aortic root
      dimension. However, only age has an important impact on aortic blood flow
      velocity in both genders.

PMID- 11515985
TI  - What is the optimal evaluation time of the QT dispersion after acute myocardial
      infarction for the risk stratification?
AB  - The sequential changes of the corrected QT dispersion (QTcD) were studied in 136
      patients 1 day to 30 days after a transmural acute myocardial infarction (AMI) to
      investigate the optimal measurement time of QT dispersion for risk
      stratification. The study group included 136 patients (89 men; mean age, 57+/-10
      years) with transmural AMI who were treated with thrombolytics (Tr+ group, n =
      73) or not (Tr- group, n = 63) and 65 healthy controls (43 men; mean age, 56+/-7
      years). Fourteen patients in whom ventricular tachycardia (VT), ventricular
      fibrillation (VF), or sudden cardiac death developed during the 30-day period
      were also evaluated as major cardiac arrhythmia (MCA) group. ECGs were obtained
      for each patient on days 1, 3, 5, 10, 15, and 30 after AMI. QTc dispersion in
      patients with AMI (for every period of QTcD after MI) was significantly more
      prolonged than in normal controls (49.3+/-16.3 ms) (p<0.001). QTcD was
      significantly greater in patients without thrombolytics than in patients with
      thrombolytics for every period (days 1, 3, 5, 10, 15, and 30) of QTcD after MI
      (p<0.001). The mean of QTcD was significantly greater in patients with MCA than
      in patients without MCA group for every period (days 1, 3, 5, 10, 15, and 30) of
      QTcD after MI (p < 0.05). Maximal QTcD was seen on day 10 (p < 0.05 1st vs day 10
      for each group) after myocardial infarction, and then reached a plateau for an
      each group. The ideal time to measure the QTD for risk stratification is at least
      10 days after AMI.

PMID- 11515986
TI  - Diabetics with hypertension not controlled with ACE inhibitors: alternate
      therapies.
AB  - If hypertension in patients with diabetes mellitus type II is not adequately
      controlled by angiotensin-converting enzyme inhibitors (ACE-i), a beta-blocker is
      frequently added as second-line therapy. Recently, large randomized trials
      demonstrated the beneficial effect of second-generation dihydropyridine calcium
      channel blockers in these patients. These compounds are increasingly being used
      to replace beta-blockers. Withdrawal of beta-blockers may influence diabetic
      control and may cause rebound hypertension. Any rebound hypertension from beta
      blocker withdrawal may not occur if the beta-blocker is replaced with a calcium
      channel blocker. A calcium-channel blocker will influence vascular resistance
      (VR) and blood pressure differently than a beta-blocker. Thirty-four patients
      with diabetes mellitus type II and a resting diastolic blood pressure above 90 mm
      Hg despite enalapril 10 mg daily (or equipotent dosages of other ACE-i) for at
      least 3 months were treated in an open label sequential comparison with the same
      ACE-i in combination with the beta-blocker metoprolol 100 mg for 3 months, and,
      subsequently for 3 more months with the same ACE-i in combination with the
      dihydropyridine calcium-channel blocker lercanidipine 10 mg once daily. After 6
      weeks, patients with a diastolic blood pressure above 90 mm Hg were titrated up
      to 200 mg metoprolol or 20 mg lercanidipine once daily. Patients were examined
      every 6 weeks during the trial, and after 2 weeks while receiving lercanidipine.
      In addition to blood pressure measurements, VR was measured by iridium strain
      gauge plethysmography and expressed in units (1 unit = 1 mm Hg/mL blood/100 mL
      tissue per minute). Two of 34 patients did not complete the protocol because of
      non-compliance with the lercanidipine treatment in the first 2 weeks of
      treatment. Their data are included in the analysis. No rebound hypertension 14
      days after the change-over of therapies was observed. (Mean arterial pressures
      [MAPs] were not significantly different from the point of withdrawal of the beta
      blockers.) However, heart rate rose from 69+/-7 to 94+/-10 beats/min (p < 0.001).
      After 3 months on lercanidipine, MAP fell by 6+/-10 mm Hg (p = 0.002) compared to
      the point of withdrawal of the beta-blocker. Vascular resistance fell by 6.28+/
      11.91 units (p<0.01), while glucosylated hemoglobin (HbA1c) rose by 0.4+/-0.5%
      (p<0.001) and body weight rose by 0.6+/-0.6 kg (p < 0.01). Multiple regression
      analysis revealed significant associations between decrease in VR, increase in
      HbAlc, and decrease in MAP, and partial dependence of these variables on one
      another. In hypertensive patients with diabetes type II, replacement of ACE-i and
      metoprolol with ACE-i and lercanidipine does not appreciably influence metabolic
      control and does not cause rebound hypertension. Lercanidipine was more effective
      than metoprolol as a second-line antihypertensive drug in these patients. At
      least two mechanisms may be involved: withdrawal of a pressor effect from the
      beta-blocker, and calcium-channel-mediated vasodilation.

PMID- 11515987
TI  - Changes of gut barrier function during anesthesia and cardiac surgery.
AB  - The aim of this clinical study was to investigate the time sequence between
      intraoperative and postoperative endotoxemia, changes in intramucosal pH(I),
      mediator release, and acute phase proteins and their relationship to
      postoperative infections. In 60 patients (median age 61 [33-72] years,
      male/female: 50/10) plasma levels of endotoxin, endotoxin neutralizing capacity
      (ENC), leukotriene-C4 (LTC4), 6-ketoprostaglandin-F-1alpha (PGF), thromboxane-B2
      (TxB2), interleukin-6 (IL-6), and C-reactive protein (CRP) were measured before,
      during, and after cardiac surgery. The intraluminal pH(I) of the stomach was
      assessed as a marker of splanchnic blood circulation. Patients were divided in
      one group with postoperative infections (group A, n = 8) and another groups
      without infections (group B, n = 52). Among all measured parameters, endotoxin
      plasma levels showed the most rapid changes. A significant increase of endotoxin
      plasma levels and a decrease in ENC appeared after the induction of anesthesia,
      culminating in a peak after reperfusion. Endotoxin showed a significantly higher
      increase in group A (14fold) compared to group B (sixfold, p<0.001), whereas ENC
      decreased by eightfold in both groups. The parameters of the arachidonic cascade
      increased and pH(I) decreased, however, there were no significant differences
      between both groups. The latest increase was observed for the acute phase
      proteins IL-6 and CRP. IL-6 levels peaked 6 hours postoperatively with a 20fold
      (group B) and 30fold (group A) increase (p < 0.001 vs baseline; no differences
      between groups), whereas CRP rose at the first postoperative day with a 21 fold
      (group B) and 25fold (group A) increase at day 2 (p<0.001 vs baseline, no
      difference between groups). Differences between both groups appeared at the
      second postoperative day for IL-6 (median values group A/B: 421/219 pg/mL; p
      <0.05) and at the fifth postoperative day for CRP (median values group A/B:
      321/81 mg/L; p < 0.05). In conclusion, endotoxin seems to be the earliest trigger
      of the mediator cascade in acute phase response and may indicate infections in
      the postoperative course.

PMID- 11515989
TI  - Hypotension and functional left ventricular obstruction during dobutamine stress
      echocardiography--two case reports.
AB  - Although hypotension during dobutamine stress echocardiography has been reported,
      the mechanism of this response is still controversial. In two patients, a 72-year
      old woman and 64-year-old man, with exercise-induced ST-T change, continuous-wave
      Doppler examination of the left ventricular cavity was performed at baseline and
      peak dobutamine infusion. No echocardiographic abnormalities at rest or
      angiographic coronary lesions were observed in either patient. The intracavitary
      pressure gradient at peak dosage of dobutamine for both patients was 121 mm Hg
      and 100 mm Hg, and was reproducibly confirmed by cardiac catheterization. During
      dobutamine infusion, echocardiography or left ventriculography revealed that
      papillary muscle motion was dramatically augmented by dobutamine and mid-left
      ventricular obstruction was produced at the systolic phase. Although blood
      pressure response improved following beta-blocker treatment, intracavitary
      pressure gradient during dobutamine infusion remained the same. A hypotensive
      response during dobutamine stress echocardiography may be produced by the
      development of dynamic intraventricular obstruction and a vasodepression reflex.
      The exercise-induced electrocardiographic changes may have been related to the
      systolic pressure augmentation in the mid-to-apical left ventricular cavity.

PMID- 11515988
TI  - Preferential acetazolamide-induced vasodilation based on vessel size and organ:
      confirmation of peripheral vasodilation with use of colored microspheres.
AB  - When carbonic anhydrase activity decreases, the regional blood flow (rBF) in
      organs increases as hypercapnia develops. However, the effects of acetazolamide
      (AZ)-induced vasodilation have not been estimated with respect to vessel size and
      organs. The aim of this study was to determine the diameter of the capillaries in
      various organs that respond to inhibition of carbonic anhydrase activity by AZ.
      White rabbits were anesthetized with urethane and ketamine and infused with AZ.
      While the systolic blood pressure (SBP), pH, hemoglobin concentration, and base
      excess did not change, the partial pressure of arterial oxygen (PaO2) increased
      significantly and the partial pressure of arterial carbon dioxide (PaCO2)
      decreased significantly with AZ. The rBF was calculated by using 3 different
      sizes (15, 25, and 50 microm) of colored microspheres (CM). The rBF measured with
      15 microm CM in the brain, kidneys, and liver increased in response to AZ, and
      the rBF in these organs was different with the different sizes of CM. However,
      the rBF calculated by using the different sizes of CM in the stomach and
      abdominal muscle did not change after the administration of AZ. The AZ-induced
      vasodilation occurred in all sizes of vessels in the liver, in the small and
      medium-sized vessels in kidneys, and in the larger capillaries in the brain.

PMID- 11515990
TI  - A unique complication during coronary angiography: peripheral embolism by
      selective right coronary engagement--a case report.
AB  - "Micro" and "macro" peripheral embolisms during coronary angiography have been
      described. In all these cases, the aorta or the left heart chambers have been the
      source of embolus. A patient who during coronary angiography for acute inferior
      myocardial infarction experienced acute embolism of the left common femoral
      artery. The source of the embolus was a thrombus-filled right coronary artery,
      and the precipitating cause was its selective engagement with a diagnostic
      Judkins right catheter. A brief review of literature is also presented.

PMID- 11515991
TI  - Large atherosclerotic left main coronary aneurysm--a case report and review of
      the literature.
AB  - Coronary artery aneurysm (CAA) is a rare disorder, characterized by an abnormal
      dilatation of a localized portion of the coronary artery. It is usually diagnosed
      incidentally by coronary angiography. Over 50% of coronary artery aneurysms are
      of atherosclerotic origin. The natural history of coronary aneurysms is not well
      understood. Their presence is not always considered to be an operative
      indication; rather, the severity of the associated coronary artery disease (CAD)
      is what dictates a surgical approach. In the absence of obstructive CAD, the
      definitive treatment for this condition is unclear. The authors present the case
      of an isolated saccular left main coronary aneurysm with no associated flow
      limiting CAD. The patient was treated medically with antiplatelet and
      anticoagulant medication with no adverse events at 3, 6, 9, and 12 months of
      follow-up.

PMID- 11515992
TI  - Regarding "cannabis arteritis revisited--ten new case reports".

PMID- 11515993
TI  - The dental school/faculty dilemma.

PMID- 11515994
TI  - Crestal bone changes around titanium implants: a methodologic study comparing
      linear radiographic with histometric measurements.
AB  - Generally, endosseous implants can be placed according to a nonsubmerged or a
      submerged technique and in 1-piece or 2-piece configurations. Recently, it has
      been shown that peri-implant crestal bone reactions differ significantly
      radiographically as well as histometrically under such conditions and are
      dependent on a rough/smooth implant border in 1-piece implants and on the
      location of a microgap (interface) between the implant and the
      abutment/restoration in 2-piece configurations. The purpose of this study was to
      evaluate whether standardized radiography as a noninvasive clinical diagnostic
      method correlates with peri-implant crestal bone levels as determined by
      histometric analysis. Fifty-nine implants were placed in edentulous mandibular
      areas of 5 foxhounds in a side-by-side comparison in both submerged and
      nonsubmerged techniques. Three months after implant placement, abutment
      connection was performed in the submerged implant sites. At 6 months, all animals
      were sacrificed, and evaluations of the first bone-to-implant contact (fBIC),
      determined on standardized periapical radiographs, were compared to similar
      analyses made from nondecalcified histology. It was shown that both techniques
      provide the same information (Pearson correlation coefficient = 0.993; P < .001).
      The precision of the radiographs was within 0.1 mm of the histometry in 73.4% of
      the evaluations, while the level of agreement fell to between 0.1 and 0.2 mm in
      15.9% of the cases. These data demonstrate in an experimental study that
      standardized periapical radiography can evaluate crestal bone levels around
      implants clinically accurately (within 0.2 mm) in a high percentage (89%) of
      cases. These findings are significant because crestal bone levels can be
      determined using a noninvasive technique, and block sectioning or sacrifice of
      the animal subject is not required. In addition, longitudinal evaluations can be
      made accurately such that bone changes over various time periods can be assessed.
      Such analyses may prove beneficial when trying to distinguish physiologic changes
      from pathologic changes or when trying to determine causes and effects of bone
      changes around dental implants.

PMID- 11515995
TI  - The use and abuse of the Periotest for 2-piece implant/abutment systems.
AB  - While the Periotest continues to be used in assessing the integrity of implants,
      there are numerous reports of its inconsistencies. To understand more precisely
      what the Periotest is actually measuring, a mathematical model was developed that
      illustrates the effect that various geometric and clinical parameters have on the
      Periotest value (PTV). In addition, the model was validated with an in vitro
      experiment. Results of the mathematical model are shown to correlate with those
      obtained from the experimental test The PTV is very sensitive to the position at
      which the Periotest impacts the abutment and to angulation of the handpiece. It
      was shown that a change in position of 1 mm in striking height can produce a
      difference in PTV of between 1 and 2. Since the angulation of the handpiece can
      produce a difference in striking position of 2 mm, it must be controlled as well.
      The model also showed that the Periotest can detect changes in bone height of 0.5
      mm.

PMID- 11515996
TI  - Analysis of Ti-6Al-4V implants placed with fibroblast growth factor 1 in  rat
      tibiae.
AB  - Titanium-aluminum-vanadium (Ti-6Al-4V) implants were placed in the tibiae of 32
      rats (male Sprague-Dawley, 350 g) to examine healing and bone response. Half of
      the implants were treated with fibroblast growth factor 1 (FGF-1) delivered in an
      activated fibrinogen matrix. Animals were injected with a radiopharmaceutical
      imaging agent, technetium-99m-methylene diphosphonate (Tc-99m-MDP), which
      concentrates in bone, especially in areas of higher osteoblastic activity.
      Binding of Tc-99m-MDP to the implant was detected in vivo by Anger gamma camera
      imaging. Fourteen days after implant surgery, specimens were recovered and
      prepared for histomorphometric analysis. Histologic examination revealed that
      samples treated with FGF-1 demonstrated significantly greater amounts of bone-to
      implant contact (P < .05) compared to controls. Also, FGF-1-treated samples
      showed significantly greater amounts of bone (percent volume) adjacent to
      implants (P < .005). These findings were supported by analyses of the non
      invasive Tc-99m-MDP images, which demonstrated significantly greater uptake of Tc
      99m-MDP adjacent to FGF-1-treated implants (P < .05). Results of the experiments
      supported the hypothesis that FGF-1 could increase bone production around
      implants in a rat model.

PMID- 11515997
TI  - Immediate postextraction implant placement with root-analog stepped implants:
      surgical procedure and statistical outcome after 6 years.
AB  - The present study investigated 124 stepped-screw implants (gritblasted and acid
      etched surface) placed in 104 patients immediately after tooth extraction or
      implant explantation and followed between August 1990 and December 1996. Implants
      of varying diameters and lengths were used to cover a wide range of indications
      in both the maxilla and mandible; 68% of the implants supported single-tooth
      replacements. The study parameters included Plaque Index, Gingival Index, probing
      depth, Periotest values, and peri-implant bone loss. Statistical analysis
      according to Kaplan-Meier revealed a 97% survival rate.

PMID- 11515998
TI  - Spontaneous early exposure of submerged endosseous implants resulting in crestal
      bone loss: a clinical evaluation between stage I and stage II surgery.
AB  - Spontaneous early exposure of submerged implants during the osseointegration
      healing phase may be a harmful factor that results in early crestal bone loss
      around the implants. The objective of this study was to assess the effect of
      spontaneous early exposure on crestal bone loss around submerged implants, with
      special attention given to the relationship between the degree of exposure and
      the amount of peri-implant bone loss. Crestal bone level relative to the shoulder
      of the implant was measured at the time of placement and at the time of exposure
      4 to 5 months later. During the period between stage I and stage II surgery,
      implant sites were observed, and each implant site in which spontaneous early
      exposure was detected was recorded. Perforations were classified according to the
      degree of implant exposure from Class 0 (no perforation) to Class IV (complete
      exposure). Measurements from 206 implants in 64 patients produced 85 groups valid
      for statistical comparison; each of these contained at least 2 lesions of
      different types. There was a statistically significant difference between bone
      loss associated with intact mucosa (Class 0) and Class I, Class II, and Class III
      lesions, and between Class I and II lesions. There were no significant
      differences between Class I and III and between Class II and III. In Class II and
      III lesions, there was more bone loss associated with the buccal aspect of the
      implants. Of the 115 perforated sites, 10 were associated with bone loss
      exceeding 2 mm, 2 presented 3 to 4 mm bone loss, 1 showed more than 4 mm, and 1
      displayed more than 5 mm. In view of the clinical implications that spontaneous
      early exposure may have on the success of osseointegration, prematurely partially
      exposed implants should be exposed as soon as possible after the perforation is
      observed.

PMID- 11515999
TI  - Influence of patient age on the success rate of dental implants supporting an
      overdenture in an edentulous mandible: a 3-year prospective study.
AB  - The aim of this study was to determine the influence of age on peri-implant
      tissues in patients treated with implant-supported overdentures in the mandible.
      A prospective study was carried out with 2 groups of healthy edentulous patients.
      The mean age of the younger group (n = 32) was 46 years (range 35 to 50 years);
      the mean age of the older group (n = 26) was 68 years (range 60 to 80 years). Two
      dental implants were placed in the interforaminal region of the mandible, and
      after a 3-month healing period, overdentures were fabricated. Clinical and
      radiographic parameters were evaluated immediately after completion of the
      prosthetic treatment, after 1 year, and after 3 years. The evaluated clinical
      parameters were implant loss, Plaque Index, Gingival Index, Bleeding Index, and
      probing depth. Radiographic evaluation was performed using a standardized long
      cone technique with a direction device. Statistical analysis was carried out with
      SPSS software. One implant in the older group was lost during the healing period.
      After 3 years, the mean scores for Plaque Index, Gingival Index, and Bleeding
      Index were between 0 and 1 for both groups (out of possible scores of 0 to 3),
      and the mean probing depth was 3 mm in both groups. The mean bone loss after 3
      years was 1.2 mm in the younger group and 0.8 mm in the older group, but this
      difference was not significant. It was concluded from this study population that
      the clinical performance of implant-supported overdentures in the mandible is
      equally successful in younger and older patients.

PMID- 11516000
TI  - A prospective human clinical trial of Endopore dental implants in restoring the
      partially edentulous maxilla using fixed prostheses.
AB  - This is the first report of a group of 50 partially edentulous patients who
      received a total of 151 Endopore dental implants in the maxilla. A mean implant
      length of 8.7 mm was used, and 76.8% of implants were placed in the posterior
      maxilla. At re-entry, all implants appeared to be osseointegrated and were used
      to support fixed prostheses. Approximately half of the crowns (57%) in these
      prostheses were splinted to one another, while the remainder (43%) were not. At
      the time of this report, the mean functional time was 34.6 months and the
      cumulative survival rate was 97.3% (4 implants had failed). Analysis of carefully
      standardized sequential radiographs indicated no significant changes in mean
      crestal bone levels between baseline and any of the examination times (after 6
      months, 1 year, and 2 years in function). There were no detectable correlations
      between crestal bone loss and the factors implant length (7, 9, or 12 mm);
      implant diameter (3.5, 4.1, or 5.0 mm); implant position anteriorly or
      posteriorly in the maxilla; or whether or not the implant-supported crowns were
      splinted.

PMID- 11516001
TI  - Implant-retained mandibular overdentures with Branemark System MKII implants: a
      prospective comparative study between delayed and immediate loading.
AB  - This study was designed to compare the results of immediate and delayed loading
      of implants with implant-retained mandibular overdentures. Ten patients (test
      group) received 40 Branemark System MKII implants (4 per patient) placed in the
      interforaminal area of the mandible. Standard abutments were immediately screwed
      to the implants, rigidly connected with a bar, and immediately loaded with an
      overdenture. Ten patients (control group) received the same type and number of
      implants in the same area, but the implants were left to heal submerged. Four to
      8 months later, standard abutments were screwed to the implants and the same
      prosthetic procedure was applied. Each implant was evaluated at the time of
      prosthetic loading and at 6, 12, and 24 months after the initial prosthetic load
      with the following parameters: modified Plaque Index (MPI), modified Bleeding
      Index (MBI), probing depth (PD), and Periotest. Peri-implant bone resorption was
      evaluated on panoramic radiographs taken 12 and 24 months after initial
      prosthetic loading. No significant differences were found between the 2 groups
      regarding MPI, MBI, Periotest, peri-implant bone resorption, and PD at 6 and 24
      months (P > .05). The only difference was found regarding PD values on the mesial
      and lingual sites at 12 months (P < .05). The cumulative success rate of implants
      was 97.5% in both groups. Results from this study showed that immediate loading
      of endosseous implants rigidly connected with a U-shaped bar does not seem to
      have any detrimental effect on osseointegration. Conversely, this method
      significantly shortens the duration of treatment with relevant satisfaction for
      the patients.

PMID- 11516002
TI  - Dimensional accuracy and retentive strength of a retrievable cement-retained
      implant-supported prosthesis.
AB  - The purpose of this research project was to compare the fit of a retrievable
      cement-retained implant-supported framework to that of a traditional wax and
      cast, screw-retained framework and to test the strength of the cemented
      restoration. Ten telescopic frameworks were luted to gold cylinders with a bis
      GMA resin cement. The control group consisted of 10 frameworks fabricated with
      traditional wax and casting techniques directly to the gold cylinders. Frameworks
      were analyzed for distortion in the z-axis using scanning electron microscopy and
      a single screw test. Results demonstrated that the retrievable cement-retained
      group had a decreased gap distance and improved angular distortion (statistical
      significance P < .01) compared to the control group. Retentive strength
      measurements for the cement-retained group with a direct pull-out test revealed a
      mean pull-out force of 65.7 kg. Three of the 5 samples surpassed the tensile
      strength of the gold retaining screws (76 kg). Cement-retained restorations
      demonstrated superior fit in the z-axis and angular distortion compared to
      traditional wax and cast screw-retained frameworks. Retentive tests support a
      simplified technique of clinically luting telescopic implant-supported frameworks
      with adequate retentive strength.

PMID- 11516003
TI  - Five-year prospective follow-up report of the Astra tech standard dental implant
      in clinical treatment.
AB  - Between 1994 and 1999, 515 Astra standard implants were placed and documented
      prospectively in 107 patients. Of these implants, 364 were placed in original
      jawbone, 38 in areas augmented with local osteoplasty, and 113 in bone grafts
      from the iliac crest. The main indications for implantation were an atrophic
      edentulous alveolar crest (n = 361) and a shortened dental arch (n = 113). Single
      tooth implants were excluded. In a special clinical examination, 56 patients with
      258 implants were investigated. The average in situ time of the implants was 34.2
      months. Failing osseointegration (n = 10), peri-implantitis (n = 10), and implant
      fracture (n = 1) in 15 patients resulted in the failure of 21 implants (4.1%).
      Three patients with 8 implants died from malignant tumor. Currently, 27 implants
      have been lost to follow-up, and 488 implants remain in situ (95.9%). Under
      analyses with different implant success criteria, the success rate decreased to
      85%. Based on the results in this patient population, this implant was found to
      be a useful alternative to established implant systems for the indications
      analyzed.

PMID- 11516004
TI  - Histologic evaluation of the osteoinductive property of autogenous demineralized
      dentin matrix on surgical bone defects in rabbit skulls using human amniotic
      membrane for guided bone regeneration.
AB  - The aim of this investigation was to evaluate the osteoinductive property of
      autogenous demineralized dentin matrix (ADDM) on experimental surgical bone
      defects in the parietal bone of rabbits using the guided bone regeneration (GBR)
      technique incorporating human amniotic membrane (HAM). Thirty-six rabbits were
      divided into 2 groups, HAM and ADDM+HAM. It was possible to conclude that HAM did
      not interfere with bone repair and was resorbed. Slices of ADDM induced direct
      bone formation and were incorporated by the newly formed bone tissue and
      remodeled. The bone defects healed faster in the ADDM+HAM group than in the group
      with HAM only.

PMID- 11516005
TI  - Treatment of peri-implant defects with the vertical ridge augmentation procedure:
      a patient report.
AB  - Most clinical patient reports apply the biologic principles of guided bone
      regeneration, in addition to defect filling with autogenous bone grafts or bone
      graft substitutes, in peri-implantitis therapy. Not infrequently, sites with
      membrane coverage have revealed early exposure, with subsequent infections,
      premature membrane removal, and insufficient bone regeneration. The present
      patient report demonstrates another surgical approach that uses the clinical
      principles and soft tissue management of vertical ridge augmentation, strictly
      following the same surgical protocol, on previously cleaned implant surfaces. The
      successful outcome of this surgical approach in one patient supports the
      feasibility of the selected treatment method in maintaining both the implants and
      the prosthetic reconstruction involved with peri-implantitis.

PMID- 11516006
TI  - Use of electrosurgery and lasers in the presence of dental implants.
AB  - Use of electrosurgery or laser surgery in the presence of metallic implants has
      been implicated in generating heat-induced injury to peri-implant bone, with the
      subsequent loss of osseointegration. Studies involving lasers offer conflicting
      results, while in the case of the electrosurg, little research has been published
      supporting or refuting these claims. This study measured local heat effects
      created by use of a unipolar electrosurgical unit, a bipolar electrosurgical
      unit, and a neodymium:yttrium-aluminum-garnet (Nd:YAG) laser. Absolute
      temperature increase was measured during an in vitro uncovering surgical
      procedure performed with each unit. Analysis of variance for repeated measures
      was performed. Second, absolute temperature increase for each unit was compared
      with a theoretical clinical limit of a 10 degrees C increase. The findings
      suggest that use of the unipolar electrosurgical unit should be avoided, while
      judicious use of both the bipolar unit or the laser unit should produce
      temperature profiles well within clinical limits.

PMID- 11516007
TI  - Development of gingival esthetics in the terminal dentition patient prior to
      dental implant placement using a full-arch transitional fixed prosthesis: a case
      report.
AB  - Despite significant advances in dental therapeutics, there are patients for whom
      no reasonable treatment is available that will reliably restore or maintain their
      existing dentition. The causes of future edentulism include advanced caries,
      failing root canal therapy, inadequate numbers of teeth to support a fixed
      prosthesis, untreatable periodontal disease, or a history of failed previous
      rehabilitations. For these patients, dental implants may provide a more
      predictable future than retention of their remaining teeth. It is proposed that
      transitional fixed prostheses designed specifically for a patient with terminal
      dentition offer the advantage of maintenance and development of proper gingival
      esthetics with improved function. Prior to implant placement, the gingival frame
      is established, enhancing the overall appearance of the final, full-arch implant
      rehabilitation. The specific prosthodontic and surgical techniques required for
      successful treatment of these patients are presented.

PMID- 11516008
TI  - Physicochemical factors affecting the sensitivity of Ceriodaphnia dubia to
      copper.
AB  - The effects of physicochemical conditions, such as pH, water hardness, flow rates
      and natural organic substances on the sensitivity of Ceriodaphnia dubia to the
      toxic effects of copper were investigated using static bioassay cups and
      specially designed flow-through bioassay chambers. We found that C. dubia was
      very sensitive to pH changes and the total copper LC50 values of C. dubia
      neonates increased by 15-fold as the pH increased from pH 7 to 10. It was also
      observed that the LC50 values increased sharply upon increasing the water
      hardness value to 2.4 meq. In addition, increasing flow rates from zero to 50 mL
      hr(-1) also increased its sensitivity to copper, which was possibly due to
      hydrodynamic stress. The presence of natural organic substances (humic acid and
      dissolved organic matter) and suspended particles decreased the toxic effect of
      copper. This significant decrease in the toxicity of copper in the presence of
      natural organic materials can be explained by a reduction in the free ion
      concentration due to complexation. Furthermore, we observed that the kinetics of
      copper interactions with natural organic materials are a significant factor in
      the toxic effect of copper and that the acute LC50 values increased with
      increasing reaction time between solubilized copper and water-borne organics.

PMID- 11516009
TI  - Monitoring requirements for groundwaters under the influence of reclaimed water.
AB  - Monitoring groundwaters under the influence of reclaimed water must consider the
      major constituents of concern in reclaimed water. This research focused on the
      fate of dissolved organic carbon and nitrogen species at field sites located
      throughout the Southwestern United States. A watershed approach was developed to
      predict the fate of dissolved organic carbon as a function of the drinking water
      dissolved organic carbon concentration and the total dissolved solids
      concentration in the reclaimed water. Extensive characterization of the dissolved
      organic carbon recovered from groundwaters under the influence of reclaimed water
      was done. With the exception of fluorescence spectroscopy, the dissolved organic
      carbon present in effluent organic matter was similar in structure, character and
      reactivity as compared to natural organic matter. Evidence for sustainable
      nitrogen removal mechanisms during groundwater recharge with reclaimed water was
      obtained. The autotrophic reaction between ammonia and nitrate appears to a
      mechanism for the removal nitrogen in a carbon-depleted environment. The
      monitoring tools and methodologies developed in this research can be used to
      assure protection of public health and determine the sustainability of indirect
      potable reuse projects.

PMID- 11516010
TI  - Effects of land use and municipal wastewater treatment changes on stream water
      quality.
AB  - This study was undertaken to analyze the quantitative impact of a municipal
      wastewater treatment operation on the long-term water quality changes in a
      tributary of the Han-river, Korea from 1994 to 1999. Changes of land use pattern
      in the study watershed are quantitatively analyzed on the basis of land use maps
      that were created by classifying Landsat TM images acquired in April 1994 and
      March 1999. During this period, the average increase of land use area in terms of
      residence, cultivation, and barren was 5.89, 0.13, and 0.12%, respectively, and
      the corresponding decrease in water and forest area was 0.21 and 0.16%. The
      annual average reductions of BOD, T-N, and T-P by the municipal wastewater
      treatment operation were about 89, 11 and 27%, respectively. Spatial analysis of
      the pollution discharge from watershed was undertaken using a geographic
      information system (GIS) based model. A clear reciprocal relationship was found
      between the basin-wide self-purification coefficient and the watershed form ratio
      excepting a catchment area with water drain facilities. Due to land use changes
      over the five year study period, water quality change in terms of BOD, T-N, and T
      P were (+)1.04 mg l(-1) (corresponding to a 13.7% increase of pollution), (+)0.58
      mgl(-1) (10.0% increase), and (-)0.01 mg l(-1) (1.6% decrease). On the other
      hand, the effect of water quality restoration assessed by outward appearance
      during the same period was about 67.6, 39, and 36.5%, respectively. Consequently,
      it is understood that total stream water quality recovery in terms of BOD, T-N,
      and T-P were 81.3, 49.0, and 38.1% respectively, and that this included a
      negative contribution resulting from increased land use and a positive
      contribution due to the wastewater treatment operation at Inchon.

PMID- 11516011
TI  - A conductive polypyrrole based ammonium ion selective electrode.
AB  - In view of the development of miniaturized sensor arrays, a solid-contact
      ammonium ion selective electrode has been investigated. A conductive polypyrrole
      film was electrochemically deposited on a glassy carbon surface and used as an
      internal solid contact layer between the sensing membrane and solid electrode
      surface. A systematic evaluation of the important parameters affecting the
      electromotive force (emf) response is presented. The performances of this solid
      contact sensor were verified using a batch-mode measurement setup and a wall-jet
      flow cell system. The designed sensor exhibited excellent selectivity for the
      primary ion and a linear response over the pNH4+ range 1-5 with a slope of 56.3
      mV decade(-1) . The sensor has a fast response and is relatively robustness, and
      was also used to determine ammonium concentrations in natural waters, with
      promising results.

PMID- 11516012
TI  - A study on hexachromic ion selective electrode based on supported liquid
      membranes.
AB  - An ion selective electrode (ISE) for determining Cr(VI) using supported liquid
      membranes (SLMs) containing trioctylphosphine oxide (TOPO) was investigated in
      this study. TOPO, as a carrier, had a high selectivity for Cr(VI) against
      interfering ions such as sulfate, nitrate, nitrite, and chloride. The composition
      of the SLM was optimized as 0.193 g TOPO/1 mL NPOE (o-nitrophenyl octyl
      ether)/0.5 g poly (vinyl chloride) for detection of Cr(VI). The Cr(VI)
      concentration was measured in the range of 1 x 10(-3) to 1 x 10(-6) M with the
      SLM prepared in the study. It seemed that Cr(VI) was transported in the SLM as a
      triply charged ion indicated by the slope of the emf response. Selectivity
      coefficients and detection limits of Cr(VI) in the presence of interfering ions
      were determined experimentally using the fixed interference method.

PMID- 11516014
TI  - Cost-effective monitoring for a soil vapor extraction (SVE) system: a simplified
      modeling and gas sensor test.
AB  - In order to establish cost-effective monitoring strategies for soil vapor
      extraction (SVE), a simplified model for multi-component mass transfer of a
      complex liquid mixture in porous media and gas sensor are proposed and
      experimentally evaluated. The basic task for the cost-effective monitoring of SVE
      is to decide how to predict the performances of venting systems in terms of the
      contaminant vapor removal rate and the time required to accomplish the clean-up
      specification. The method includes classifying of individual components of a
      complex mixture on the basis of gas chromatographic (GC) profile and treating
      each resulting group as a pseudo-single compound. BTEX components of gasoline
      were selected for model input and the remainders were divided into 4 groups based
      on their GC retention times. The model proposed in this study is capable of
      predicting with accuracy volatilization behaviors of gasoline components in soil
      and the gas sensor (FIGARO TGS 823) was tested by GC-FID to toluene and TPH
      GRO(Total Petroleum Hydrocarbon-Gasoline Range Organics) gas samples. A VOC gas
      sensor was developed which recognizes TPH-GRO concentrations between 250 and 50
      ppm. The developed gas sensor test and proposed model can be used as a valuable
      tool for the cost-effective monitoring for SVE systems.

PMID- 11516013
TI  - Environmental monitoring of heavy metals and arsenic from Ag-Pb-Zn mining: a case
      study over two millennia.
AB  - 2000 years of mining activity at Wiesloch, Germany left behind a legacy of mining
      wastes, some of which have extremely high contents of toxic elements like As, Cd,
      Tl, Sb, Pb and Zn. To evaluate their long-term impact on different environmental
      compartments, the detailed environmental monitoring presented here focused on the
      mineralogical and chemical characterization of the different waste materials,
      consisting of dumpings with ore fragments, flotation tailings and medieval
      metallurgical slags. Leaching experiments with these materials, using eluents of
      different compositions and pHs were carried out to assess the conditions
      governing the mobilization and re-fixation of these species. It was shown, that
      the carbonate host rock of the mineralization, the loess blanket covering the
      area and the organically rich municipal sewage sludges deposited on top of the
      tailings, represent potential barriers to the dispersion of toxic elements over a
      much larger area. Moreover, particulate emissions from the steep, unvegetated
      escarpments of the tailing heaps represent a continuous thread to the
      environment.

PMID- 11516015
TI  - Surface measurements of global warming causing atmospheric constituents in Korea.
AB  - The expansion of the industrial economy and the increase of population in
      Northeast Asian countries have caused much interest in climate monitoring related
      to global warming. However, new techniques and better platforms for the
      measurement of global warming and regional databases are still old-fashioned and
      are not being developed sufficiently. With respect to this agenda, since 1993, at
      the request of the World Meteorological Organization (WMO), to monitor functions
      of global warming, the Korea Meteorological Administration (KMA) has set up a
      Global Atmospheric Watch (GAW) Station on the western coast of Korea (Anmyun-do)
      and has been actively monitoring global warming over Northeast Asia. In addition,
      atmospheric carbon dioxide (CO2) has been measured for a similar KMA global
      warming program at Kosan, Cheju Island since 1990. Aerosol and radiation have
      also been measured at both sites as well as in Seoul. The observations have been
      analyzed using diagnostics of climate change in Northeast Asia and also have been
      internationally compared. Results indicate that greenhouse gases are in good
      statistic agreement with the NOAA/Climate Monitoring and Diagnostics Laboratory
      (CMDL) long-term trends of monthly mean concentrations and seasonal cycles.
      Atmospheric particulate matter has also been analyzed for particular Asian types
      in terms of optical depth, number concentration and size distribution.

PMID- 11516016
TI  - Monitoring and modeling of disinfection by-products (DBPs).
AB  - In the United States, the newly promulgated disinfectant/disinfection by-product
      (D/DBP) regulations force water treatment utilities to be more concerned with
      finished and distributed water qualities. In this study, monitoring of DBP
      formation was conducted from three French water treatment plants trying to assess
      DBP variations through time and space. Compared to the in-plant total
      trihalomethanes (TTHM) levels, TTHM levels in the distribution system increased
      from less than 150% to more than 300%. Significant variations for TTHM and
      bromate (BrO3-) levels throughout the seasons were also observed; generally
      higher levels in the summer and lower levels in the winter. Combining chemical
      DBP models (empirical power functional models) and hydraulic simulations, DBPs
      including TTHM and BrO3- were successfully simulated from the full-scale
      monitoring data, indicating that empirical DBP model can be a potential tool to
      access DBP formation in actual plants. This study also provides the protocols to
      assess DBP simulations in the water treatment systems.

PMID- 11516017
TI  - Activity monitoring for nitrifying bacteria by fluorescence in situ hybridization
      and respirometry.
AB  - The activities of two families of nitrifying bacteria were measured by applied
      respirometer and fluorescence in situ hybridization (FISH) for the purpose of
      monitoring nitrogen removal. Oxygen uptake rates (OUR) for Nitrosomonas and
      Nitrobacter were separately measured with the dosing of selective inhibitors
      during respirometric monitoring. The FISH method was applied to analyze
      microorganism communities. In 5 mg NH4+-N/L solution, the total nitrogen oxygen
      demand (NOD) was found to be 6,672 mg DO/L-day with ammonia and nitrite oxidation
      rate of 4,512 and 2,160 mg DO/L-day, respectively. The oxygen consumption by
      endogenous oxidation was 288 mg DO/L-day and the biological oxygen demand 936 mg
      DO/L-day. Respirometric measurements were well matched by the FISH result, which
      described the presence and quantity of each nitrifying bacteria as nitrification
      proceeded. It was found that when coupled with OUR data, FISH could provide
      valuable information about the nitrogen removal process in many practical
      wastewater treatment systems.

PMID- 11516018
TI  - Development of monitoring technology for airborne particulate matter.
AB  - Particulate matter suspended in the air has adverse effects on human health. Its
      level of concentration is an important parameter in evaluating the degree of
      hazard it poses to the atmosphere. Conventional methods used in measuring
      particulate matter are often filter-based, which indicates some disadvantages
      because such a base requires labor and time. In this study, to achieve real-time
      measurements, a new electrical method was developed for measuring PM10 and PM2.5
      concentrations. The basic principle is to electrically charge particles passing
      through the PM inlet using a corona charger and measure the currents created by
      charged particles to obtain the number concentration of particulate matter. A new
      type inlet based on the particle cup impactor configuration was designed and its
      performance was evaluated. A unipolar diffusion charger was developed and the
      charger's efficiency was determined experimentally in terms of Pn, which
      represents the penetration through the charger, P, times the average charge
      number acquired by a particle, n, for different particle sizes. The correlation
      was constructed between the PM 10 (or the PM2.5) mass concentrations and the
      electrical currents due to particles, which were charged by the diffusion
      charger.

PMID- 11516019
TI  - Seasonal characteristics of haze observed by continuous visibility monitoring in
      the urban atmosphere of Kwangju, Korea.
AB  - Continuous visibility monitoring has been carried out in Kwangju, Korea since May
      1999. The total light extinction coefficient bext measured by a transmissometer
      and reveals seasonal trends in urban visual air quality, especially under hazy
      conditions with a visual range of less than 15 km. Seasonal atmospheric
      visibility under low relative humidity during the winter was observed to be
      better than during any other seasons. Summertime visibility was severely degraded
      due to highly increased light scattering by hygroscopic particles under high
      humidity atmospheric conditions. Visibility during spring and fall was also
      moderate. However, yellow sand in spring caused the lowest visibility conditions
      over the measurement area for a few days. With continuous monitoring using the
      transmissometer, the daily average seasonal visual range was measured to be 13.1,
      9.2, 11.0, and 13.9 km in spring, summer, fall and winter, respectively. Under
      the atmospheric humidity condition less than 60%, visual range was observed to be
      16.1, 13.9, 15.1, and 16.6 km in spring, summer, fall, and winter, respectively.
      The mean light extinction budget by sulfate and nitrate aerosols was determined
      to be the highest value of 63.71% during the summer and the lowest value of
      27.08% during spring. During the 'yellow sand dust' period, a mean light
      extinction budget by soil particles was estimated to be at an unusually high
      value of 44.22%.

PMID- 11516020
TI  - Background monitoring and long-range transport of atmospheric CFC-11 and CFC-12
      at Kosan, Korea.
AB  - The background concentrations of atmospheric CFC-11 and CFC-12 were monitored to
      assess their impact on stratospheric ozone depletion and global warming from
      September 1995 to March 1999 at Kosan, Korea, located at eastern margin of the
      Asian Continent. The concentrations of atmospheric CFC-11 at Kosan have decreased
      slightly, at a rate of -2.5 pptv yr(-1), over the period in response to the
      Montreal Protocol. The CFC-12 mixing ratio at Kosan continues to increase in the
      atmosphere at a rate of 5.7 pptv yr(-1) despite international regulations,
      because of its extreme atmosphere persistence. Recent trends of these two
      chlorofluorocarbons at Kosan, Korea were concordant with those of the northern
      hemispheric background monitored unit at Mauna Loa, Hawaii. The maximum seasonal
      mean mixing ratios of CFC-11 and CFC-12 at Kosan, Korea, were 270 +/- 4 pptv in
      the spring and 538 +/- 9 pptv in the winter, and the corresponding seasonal
      minima were 267 +/- 7 and 529 +/- 12 pptv. This occurred in the summer and was
      due to southeasterly winds from the northwestern Pacific Ocean. By performing a
      three-day isentropic backward trajectory analysis, it was shown that air masses
      at Kosan, and with the exception of summer, mainly originated from central and
      northern China. In particular, the mixing ratios of these two contaminant species
      are closely related with their air mass trajectories.

PMID- 11516021
TI  - Cultured human-cell-based bioassay for environmental risk management.
AB  - Among bioassays for evaluating various impacts of chemicals on humans and
      ecosystems, those based on cultured mammalian-cells can best predict acute lethal
      toxicity to humans. We expect them to be employed in the future in environmental
      risk management alongside mutagenicity tests and endocrine-disrupting activity
      tests. We recently developed a disposable bioassay device that immobilizes human
      hepatocarcinoma cells in a small micropipette tip. This enables very quick
      (within 2 h) evaluation of acute lethal toxicity to humans. For bioassay-based
      environmental management, 2 promising approaches have been demonstrated by the US
      EPA: toxicity identification evaluation (TIE) and toxicity reduction evaluation
      (TRE). The Japanese Ministry of Environment has been supporting a multi-center
      validation project, aimed at assembling a bioassay database. To make full use of
      these resources, we present a numerical model that describes contribution of
      individual chemical to observed toxicity. This will allow the selection of the
      most effective countermeasure to reduce the toxicity. Bioassay-based
      environmental risk management works retrospectively, whereas impact assessment
      using substance flow models and toxicity databases works prospective. We expect
      that these 2 approaches will exchange information, act complementarily, and work
      effectively in keeping our environment healthy in the 21 st century.

PMID- 11516023
TI  - Detection of hormone mimics in water using a miniturised SPR sensor.
AB  - The ubiquitous presence of chemicals, both natural and synthetic, in the
      environment with the potential to mimic hormones that may in turn interfere with
      the endocrine system in both wildlife and humans has in the last decade become a
      major international concern. Hormone mimics or endocrine disrupting compounds
      (EDCs) are especially prevalent in surface and waste-waters and therefore, there
      is a need for an at-source or at-line analytical device for the monitoring of EDC
      levels. We have incorporated a miniature integrated surface plasmon resonance
      (SPR) liquid sensor from Texas Instruments into a field analyser and developed a
      competition/inhibition assay for a model estrogenic compound in aqueous samples.
      The analyser has the potential for in situ and semi-continuous analysis of EDCs.
      A novel regeneration scheme employing the use of a domestic laundry detergent has
      been used to remove immobilised assay components between each assay cycle. The
      resultant re-usable sensor has been demonstrated using estrone-3-glucuronide
      (E3G) as a model EDC and an anti-E3G antibody producing a current detection range
      of 10 to 150 ng mL(-1).

PMID- 11516022
TI  - The continuous monitoring of field water samples with a novel multi-channel two
      stage mini-bioreactor system.
AB  - Toxicity monitoring of field water samples was performed using a novel multi
      channel two-stage mini-bioreactor system and genetically engineered
      bioluminescent bacteria for the continuous monitoring and classification of the
      toxicity present in the samples. The toxicity of various samples spiked with
      known endocrine disrupting chemicals and phenol was also investigated for system
      characterization. The field samples used in this study were obtained from two
      different sites on a monthly basis--from a drinking water treatment plant,
      referred to as site N, and from a stream near a dam which is currently being
      constructed, referred to as site T. These samples were either pumped or injected
      into the second mini-bioreactors to initiate the toxicity test. Most of the
      samples did not show any specific toxicity. However, one sample showed to have,
      based upon the detection results, and was deemed toxic. The samples spiked with
      phenol showed possible responses in the DPD2540 and TV1061 channels, indicating
      the occurrence of both membrane and protein damage due to phenol. In the tests
      using an endocrine disrupting chemical, bisphenol A, DNA damage was detected in
      the DPD2794 channel with a concentration of 2 ppm. Finally, a simple but novel
      early warning protocol that can be used in a drinking water reservoir and a
      suspected place where effluents of toxic materials enter the water sourse was
      suggested with a schematic diagram. In conclusion, this system showed good
      feasibility for use as a toxicity monitoring system in the field and as an early
      warning system, indicating if effluents are toxic.

PMID- 11516024
TI  - Ecotoxicity monitoring of hydrocarbon-contaminated soil using earthworm (Eisenia
      foetida).
AB  - In order to assess the applicability of an earthworm bioassay as a technique for
      monitoring the soil flushing process, short-term and long-term toxicity tests
      were conducted on remediated soil using various pore volumes of surfactant
      solution. Results obtained on short-term toxicity testing indicated that biomass
      increased as the soil flushing proceeded, and on diesel-contaminated soils this
      testing showed that the effect of diesel is lethal and that 25 pore volumes of
      soil surfactant were not sufficient to abrogate the toxic effect of diesel. These
      short-term tests also showed strong sublethal relationships between the
      development of biomass, and the concentrations of toxic chemicals in the soil.
      Although relationships between contaminants and the various bioassay parameters
      examined were not significant in long-term testing, an increase in the number of
      juveniles was observed over time, which may have been a consequence of a
      reduction in toxicity associated with the flushing process.

PMID- 11516025
TI  - Elective stenting in small coronary arteries: lessons learnt from recent trials.

PMID- 11516026
TI  - Coronary artery disease in women.

PMID- 11516027
TI  - Mechanisms of sudden cardiac death: a review of investigative approaches for a
      global dilemma.

PMID- 11516029
TI  - Coronary stent implantation without lesion predilatation (direct stenting): our
      experience with this evolving technique.
AB  - BACKGROUND: Until recently, conventional intracoronary stent deployment required
      predilatation of the lesion with a balloon. However, "direct stenting" of the
      lesion without predilatation offers certain theoretical and practical advantages.
      We assessed the safety and feasibility of direct stenting in a select group of
      patients who were likely to benefit most from these advantages, namely, those
      with acute coronary syndromes. saphenous vein graft lesions, associated renal or
      left ventricular dysfunction and those requiring multivessel intervention.
      METHODS AND RESULTS: After direct stenting, intravascular ultrasound was used to
      assess the adequacy of stent expansion in 51 patients. One hundred and twenty
      patients with a total of 125 lesions (83.3% males, average age 54.6+/-12.4 years)
      were enrolled for direct stenting. Of these, 90% of patients had presented with
      acute coronary syndromes, 21.6% of patients had associated moderate-to-severe
      left ventricular systolic dysfunction, 6.7% of patients had associated renal
      dysfunction and 30.8% of patients required multivessel intervention.
      Angiographically visible thrombus was present in 35.2% of patients. The mean
      reference diameter of the lesion was 3.18+/-0.32 mm and mean percentage diameter
      stenosis was 76.4+/-11.2%. Almost all varieties of stents were used (8.8% bare
      and 91.2% mounted). Procedural success was achieved in 98.3% of patients (98.4%
      of lesions). In two cases, the lesion had to be predilated prior to stenting. On
      angiography, the need for postdilatation of the stent was apparent in 29 (23.6%)
      lesions. In contrast, on intravascular ultrasound evaluation done in 51 lesions
      after stent deployment, the need for postdilatation to optimize stent expansion
      was seen in 43 (84.3%) lesions. There was one instance of acute stent thrombosis
      and two instances of slow-flow phenomenon. There were no deaths, myocardial
      infarction or need for urgent bypass surgery. CONCLUSIONS: We conclude that
      direct stenting is feasible and safe in selected groups of patients. Optimization
      of stent expansion after direct stenting may often require aggressive
      postdilatation.

PMID- 11516028
TI  - Neurohumoral activation in percutaneous coronary interventions: apropos of ten
      vasoactive substances during and immediately following coronary rotastenting.
AB  - BACKGROUND: Ischemia, left ventricular dysfunction, endothelial damage and
      hemodynamic changes during percutaneous coronary intervention can lead to
      neurohumoral activation. This may partly explain the frequent episodes of
      coronary spasm, hypotension and bradycardia which occur during the procedure.
      Rotastenting, by employing the two basic mechanisms for coronary interventions
      debulking and dilatation-epitomizes percutaneous coronary interventions in
      general. We sought to investigate the neurohumoral changes during and immediately
      following coronary rotastenting. METHODS AND RESULTS: Eighteen patients
      undergoing elective rotablator atherectomy followed by balloon predilatation and
      stenting for chronic stable angina were studied. Four femoral vein blood samples
      were drawn from each patient at the start of the intervention (baseline), and 2
      (postdebulking-2), 10 (postdebulking-10) and 60 (postdebulking-60) minutes.
      respectively, after the first complete passage of the rotablation burr across the
      whole length of lesion. Levels of 10 neurohormones, namely, endothelin-1,
      bradykinin, arginine vasopressin, norepinephrine, dopamine, epinephrine,
      angiotensin II, serum angiotensin-converting enzyme activity. atrial natriuretic
      peptide and kininogen were estimated in each sample. Endothelin-1 and bradykinin
      attained their peak levels in the postdebulking-2 samples. and the rise from
      0.34+/-0.07 pmol/ml and 235.8+/-17.7 pg/ml to 0.42+/-0.06 pmol/ml and 337.2+/
      41.0 pg/ml, respectively, was statistically significant (p<0.05). The level of
      arginine vasopressin showed a significant (p<0.05) rise from baseline (108.5+/
      31.8 pg/ml) to postdebulking-60 samples (136.5+/-39.4 pg/ml). The other
      neurohormones did not show significant changes. CONCLUSIONS: The results suggest
      a definite but differential neurohumoral activation during and immediately
      following rotastenting. These neurohumoral changes may have a role in untoward
      intra- and postprocedural vasomotor and hemodynamic effects. This study
      establishes the concept of neurohumoral activation during percutaneous coronary
      interventions.

PMID- 11516030
TI  - Is off-pump coronary artery bypass surgery safe for left main coronary artery
      stenosis?
AB  - BACKGROUND: The feasibility of off-pump coronary artery bypass surgery has been
      well demonstrated. The purpose of the present study was to assess the safety and
      efficacy of off-pump coronary artery surgery in patients with left main coronary
      artery disease. METHODS AND RESULTS: Between January 1997 and December 2000, 174
      patients with significant left main coronary artery stenosis underwent coronary
      artery bypass grafting without a pump. During the same period, 991 patients who
      also had significant left main coronary artery stenosis underwent coronary artery
      surgery on a pump. The patients in the two groups were matched in preoperative
      variables except that those in the off-pump group were slightly older, and more
      required urgent surgery. Hospital mortality was 2/174 and 21/991 in the off-pump
      and on-pump groups, respectively (p=0.560). The incidence of perioperative
      myocardial infarction (1.74 v. 14/991, p=0.712), atrial fibrillation (17/174 v
      157/991, p=0.050) and blood transfusion requirement (63/174 v. 476/991, p=0.05)
      were significantly less in the off-pump group. The intubation time (15+/-3 hours
      v 22+/-4 hours, p=0.001), blood loss (365+/-61 ml v 582+/-76 ml, p<0.001),
      intensive care unit stay (23+/-10 hours v. 36+/-11 hours, p<0.001) and hospital
      stay (6+/-4 days v. 9+/-5 days, p <0.001) were also less in the off-pump group.
      CONCLUSIONS: Off-pump coronary artery bypass surgery is safe and effective for
      patients with left main coronary artery disease.

PMID- 11516031
TI  - Surgical experience with dissecting and nondissecting aneurysms of the ascending
      aorta.
AB  - BACKGROUND: Patients who underwent replacement of the ascending aorta with a
      prosthetic graft for treatment of ascending aortic aneurysm and dissection
      between January 1992 and December 2000 were studied. METHODS AND RESULTS:
      Bentall's operation, using a composite aortic valve and prosthetic graft. was
      performed in 82 patients (70 males). Indications for the procedure included
      ascending aortic aneurysm (n=54 including 16 patients with Marfan's syndrome):
      DeBakey Type I or II aortic dissection (n=26 including 10 patients with Marfan's
      syndrome) and ascending aortic aneurysm with severe aortic stenosis (bicuspid
      aortic valve disease) (n=2). Bentall's procedure with the inclusion technique was
      performed in 72 patients and a Cabrol fistula created in 63 patients. In 10 other
      patients, coronary button transfer was done without a Cabrol fistula. There were
      6 early deaths (7.3%) and 8 patients required re-exploration for excessive
      bleeding. Eighteen patients showed low cardiac output while the wound of 8 became
      infected. Postoperative arrhythmia and renal failure was seen in 26 and 6
      patients, respectively. Four patients had pericardial effusion. Follow-up ranged
      from 1 month to 8 years. There were 8 late deaths, the causes of which include
      congestive heart failure (n=3). cerebral hemorrhage (n=3) and sudden cardiac
      death (n=2). Two patients reported back with dissection of the descending
      thoracic aorta and await surgery. CONCLUSIONS: Bentall's operation is a safe
      procedure with an acceptable mortality and morbidity.

PMID- 11516032
TI  - Prescribing patterns and cost of antihypertensive drugs in an internal medicine
      clinic.
AB  - BACKGROUND: Antihypertensive agents are selected primarily for their ability to
      prevent morbidity and mortality related to hypertension. METHODS AND RESULTS:
      Prescribing trends and the cost of antihypertensive drugs were studied in 300
      patients attending an internal medicine clinic. Beta-blockers were the most
      frequently used group of drugs (46.7%), followed by calcium-channel antagonists
      (34.3%) and angiotensin-converting enzyme inhibitors (30%). Diuretics were used
      in only 13.2% of the prescriptions. Atenolol (36%), amlodipine (29.3%) and
      enalapril (19%) were the most frequently used individual drugs. Propranolol,
      furosemide, amlodipine and atenolol were the least expensive drugs used, with
      annual drug acquisition costs of Rs 80, 102, 182 and 318, respectively.
      Benazepril (Rs 1778), diltiazem SR (Rs 1777), lisinopril (Rs 1660), prazosin (Rs
      1416) and losartan (Rs 1365) were the most expensive drugs in terms of annual
      drug acquisition costs. CONCLUSIONS: The results of our study emphasize the need
      to encourage frequent use of diuretics. Since the costs of different
      antihypertensives vary considerably, newer and relatively expensive
      antihypertensives should be prescribed only when clearly indicated.

PMID- 11516033
TI  - Serous fluid leakage following modified Blalock-Taussig operation using PTFE
      grafts.
AB  - BACKGROUND: Serous fluid leakage is an unusual but often devastating complication
      following the placement of a modified Blalock-Taussig shunt using a
      polytetrafluoroethylene graft. METHOD AND RESULTS: Between September 1994 and
      September 1999, out of 268 patients undergoing a modified Blalock-Taussig shunt
      using polytetrafluoroethylene grafts, 10 developed massive pleural effusion or
      seroma due to a leak from the surface of the shunt. The age of the patients
      ranged from 9 days to 7 years. There were 7 males and 3 females. Nine patients
      presented with respiratory distress between 2 and 12 weeks of shunt surgery and
      one presented with sudden cardiac arrest. The shunt was patent in all the
      patients. Initial management was conservative. i.e. by pharmacological means and
      tube thoracostomy. Reoperation was undertaken in 9 patients when conservative
      treatment failed. All patients survived except one who had a cardiac arrest
      before any intervention could be carried out. CONCLUSIONS: Patients with serous
      effusion have significant morbidity and mortality and often require reoperation.
      The initial management remains conservative but, if unsuccessful, re-exploration
      can be undertaken as it proved to be uniformly successful in our experience.

PMID- 11516035
TI  - Transcatheter fenestration of a total cavopulmonary connection baffle.
AB  - Transcatheter creation of a de novo fenestration of a total cavopulmonary
      connection baffle has not been previously reported from India. We present our
      experience with such a procedure in a 4-year-old child with recurrent pleural
      effusions in the early postoperative period.

PMID- 11516034
TI  - Lipid abnormalities in coronary heart disease: a population-based case-control
      study.
AB  - BACKGROUND: We performed a case-control study to estimate lipid-cholesterol
      fractions in patients with coronary heart disease and compared them with
      population-based controls. METHODS AND RESULTS: A total of 635 newly diagnosed
      patients with coronary heart disease (518 males and 117 females) and 632 subjects
      (346 males and 286 females) obtained from an ongoing urban coronary heart disease
      risk factor epidemiological study were evaluated. Age-specific lipid values
      (total cholesterol, low-density lipoprotein, high-density lipoprotein,
      triglycerides, and total:high-density lipoprotein cholesterol ratio) were
      compared using the t-test. Age-adjusted prevalence of dyslipidemia as defined by
      the US National Cholesterol Education Program was compared using the Chi-square
      test. In all the age groups, and in both males and females, levels of total and
      low-density lipoprotein cholesterol were not significantly different. In males,
      the high-density lipoprotein cholesterol (mg/dl) was significantly lower in
      patients with coronary heart disease as compared to controls in the age groups 30
      39 years (35.1+/-11 v. 43.7+/-9), 40-49 years (39.0+/-10 v. 47.1+/-8), 50-59
      years (38.9+/-11 v. 43.8+/-9) and 60-69 years (38.6+/-11, v. 42.8+/-7) (p<0.05).
      In females, high-density lipoprotein cholesterol was less in the age groups 30-39
      years (30.2+/-9 v. 40.7+/-9), 50-59 years (39.7+/-12 v. 44.7+/-8) and 60-69 years
      (35.6+/-11 v. 42.2+/-9). The level of triglycerides was significantly higher in
      male patients in the age groups 40-49 years (195.3+/-96 v. 152.8+/-78), 50-59
      years (176.7+/-76 v. 162.9+/-97), 60-69 years (175.5+/-93 v. 148.1+/-65) and >70
      years (159.8+/-62 v. 100.0+/-22); and in female patients in the age group 30-39
      years (170.8+/-20 v. 149.9+/-9) (p<0.05). The total:high-density lipoprotein
      cholesterol ratio was significantly higher in all age groups in male as well as
      female patients with coronary heart disease (p<0.05). CONCLUSIONS: An age
      adjusted case-control comparison showed that the prevalence of hypertension,
      diabetes, high total cholesterol (> or =200 mg/dl) (males 48.8% v. 20.2%; females
      59.8% v. 33.4%) and high low-density lipoprotein cholesterol (> or =130 mg/dl)
      (males 42.1% v. 15.0%; females 52.1% v. 31.0%) was significantly more in cases
      than in controls. The prevalence of low high-density lipoprotein cholesterol (<35
      mg/dl) (males 39.6% v. 6.2%; females 39.3% iv 9.5%), high total:high-density
      lipoprotein ratio (> or = 5.0) and high triglycerides (> or =200 mg/ dl: males
      39.6%, v. 10.2%; females 17.1% v. 11.9%) was also significantly higher in cases
      (p<0.05).

PMID- 11516036
TI  - Spontaneous resolution of intramyocardial hematoma of the left ventricle.
AB  - A 40-year-old male with hematoma of the left ventricular myocardium is described.
      On echocardiography, the hematoma was initially diagnosed as a cyst-like
      structure located at the apex and adjoining anterolateral wall of the left
      ventricle. A contrast-enhanced computerized tomography scan and magnetic
      resonance imaging further confirmed this lesion to be a hematoma. On follow-up,
      the hematoma gradually subsided and could not be seen on a repeat
      echocardiography and computerized tomography scan at four weeks.

PMID- 11516037
TI  - Intravascular ultrasound-guided angioplasty and stenting in a case of transplant
      coronary artery disease.
AB  - Allograft vasculopathy in cardiac transplant recipients occurs commonly at 5
      years post transplantation. We report a case of post-transplant right coronary
      discrete stenosis which was treated with balloon angioplasty and stent
      implantation under intravascular ultrasound guidance.

PMID- 11516038
TI  - Ross procedure in an infant.
AB  - The Ross procedure is gaining acceptance as the procedure of choice for aortic
      valve replacement in children. We present the case of a 4-month-old child (weight
      3.2 kg) suffering from congenital valvar aortic stenosis who underwent a Ross
      procedure. We believe that this is the youngest patient to have undergone this
      procedure successfully in the Indian subcontinent.

PMID- 11516039
TI  - Aortoarteritis presenting with hypoparathyroidism.
AB  - Clinical manifestations of aortoarteritis (Takayasu's arteritis) are varied,
      depending on the involved segment of the aorta and its branches. A case of a
      young Indian woman with aortoarteritis presenting primarily with
      hypoparathyroidism is reported. Aortogram showed total occlusion of the arch
      arteries. To the best of our knowledge, the occurrence of hypoparathyroidism in
      aortoarteritis has not been reported. Possible mechanisms of such an involvement
      are discussed.

PMID- 11516040
TI  - Infective endocarditis due to an unusual serotype of Salmonella.
AB  - Salmonellae are a rare cause of infective endocarditis. We report a case in which
      Salmonella enterica serotype Worthington was isolated from a case of
      endocarditis. The isolate was resistant to ampicillin, gentamicin, amikacin and
      chloramphenicol and sensitive to ciprofloxacin and cefotaxime.

PMID- 11516041
TI  - Absent coronary venous sinus: a rare anomaly.
AB  - A 42-year-old man, presenting with dyspnea on exertion and ST segment depression
      on treadmill test, was found to have absent coronary venous sinus on coronary
      angiography. We report this case of isolated congenital absence of coronary
      venous sinus because of its rarity.

PMID- 11516042
TI  - Newer antiarrhythmic drugs.

PMID- 11516043
TI  - Treatment of hypertension in patients with diabetes mellitus.

PMID- 11516044
TI  - Extrathoracic subclavian venepuncture for pacemaker implantation.

PMID- 11516045
TI  - Extensive arterial calcification in aortoarteritis.

PMID- 11516046
TI  - Randomized, single-blind, placebo-controlled pilot study of catheter-based
      myocardial gene transfer for therapeutic angiogenesis using left ventricular
      electromechanical mapping in patients with chronic myocardial ischemia.

PMID- 11516047
TI  - Stenting versus thrombolysis in acute myocardial infarction trial (STAT).

PMID- 11516048
TI  - Novel dosing regimen of eptifibatide in planned coronary stent implantation
      (ESPRIT): a randomized placebo-controlled study.

PMID- 11516049
TI  - The CGHA asthma management program and its effect upon pediatric asthma admission
      rates.
AB  - Asthma is the most common reason for admission to the hospital for children
      nationally. This hospitalization rate is stable despite availability of
      appropriate outpatient treatments. Our Cincinnati Group Health Associates (CGHA)
      asthma management program has evolved since 1989. We have measured our pediatric
      population along with asthma admissions since 1993. Our admission pattern is
      compared to the community in general and to our managed care population in
      particular. Our urban center's admission pattern is also studied. Our CGHA
      pediatric asthma admissions have been declining steadily over the 1993-2000
      period by 60%. This decrease is in contrast to national trends in this time
      period. Comparison to total admissions from 1993 through 2000 still shows a 50%
      decline whether 0-18 years or 0-5 years is studied. Our urban pediatric center
      also had a fall in pediatric asthma admission rates of 80% in this time frame;
      all of these results are statistically significant. Our major managed care
      network also showed a decline of 55% in pediatric asthma admissions from 1996 to
      1999. Our CGHA asthma management program has had a positive influence on our
      pediatric asthma admission rates. This effect is favorable in comparison to
      national trends in pediatric asthma admissions. This trend is independent of
      disease acuity, region of the city where patients live, insurance selection, or
      age.

PMID- 11516050
TI  - Parental opinions regarding poliomyelitis immunizations.
AB  - The successful eradication of poliomyelitis in the United States has primarily
      been due to the use of oral poliovirus vaccine (OPV). However, because of the
      risk of vaccine-associated paralytic poliomyelitis with OPV, the use of
      inactivated poliovirus vaccine (IPV) has become the accepted option. We performed
      a cross-sectional survey of parents of children less than 18 months of age to
      determine parental preference regarding poliomyelitis vaccine options. Parents
      were asked questions about their knowledge regarding poliomyelitis and available
      vaccines. Parents were also given information about the risks and benefits of the
      3 immunization options (all OPV, all IPV, and sequential IPV/OPV) and then asked
      to choose among the 3 schedules. We distributed 146 questionnaires, with an 88%
      response rate. Parents were, on average, 22 years old and had 12 years of
      education. Fifty-eight percent of parents thought that decisions regarding
      vaccine choices should be made by the physician and caregiver together. However,
      when given the choice, 41 % could not decide among the different vaccine options.
      One quarter (25%) chose the all OPV, 13% the all IPV, and 21% the sequential
      IPV/OPV schedule. Older parents were more likely to choose the all IPV schedule
      (p=0.042). There was no correlation with the parental level of education. More
      studies are required to determine if further education will empower urban parents
      to be more active participants in the medical decision process.

PMID- 11516051
TI  - Growth hormone replacement therapy in children with leukemia in remission.
AB  - We describe a patient with leukemia in remission for 7 years who developed growth
      hormone (GH) deficiency and was treated with recombinant human growth hormone
      (rhGH). We compare her growth with that of patients from the National Cooperative
      Growth Study (NCGS) database, 145 with leukemia in remission and 725 with
      idiopathic growth hormone deficiency (IGHD) on treatment with rhGH. We also
      review the literature on the risk of relapse of leukemia in similar patients. The
      patients with leukemia in remission from the NCGS database had a significantly
      lower change of mean height standard deviation score than that of IGHD patients
      in the first, second, and third year of rhGH treatment. The relapse rate of
      leukemia in patients treated with rhGH is between 0.8% and 2%. Starting rhGH
      therapy in patients with leukemia in remission and with GH deficiency at an
      adequate dosage and without undue delay would improve their growth response. Such
      therapy does not appear to increase the risk of leukemia.

PMID- 11516052
TI  - Self-hypnosis for the treatment of functional abdominal pain in childhood.
AB  - Functional abdominal pain, defined as recurrent abdominal pain in the absence of
      an identifiable physiologic cause, can respond to psychological intervention in
      appropriate patients. In this patient series, functional abdominal pain of 4 of 5
      pediatric patients resolved within 3 weeks after a single session of instruction
      in self-hypnosis. The potential impact of widespread application of such
      hypnotherapy may be large, because abdominal pain is thought to be the most
      common recurrent physical symptom attributable to psychological factors among
      children and adolescents.

PMID- 11516053
TI  - Passive otic indigenous noise transmission: a new technology for the diagnosis of
      middle ear effusion.

PMID- 11516054
TI  - Syncope in adolescent girls.

PMID- 11516055
TI  - Child abuse by percutaneous insertion of sewing needles.

PMID- 11516056
TI  - Communication with postpartum mothers: are we competing with the television?

PMID- 11516057
TI  - Vomiting and gastric motility in infants with cow's milk allergy.

PMID- 11516058
TI  - Treatment of recurrent abdominal pain: components analysis of four treatment
      protocols.

PMID- 11516059
TI  - Empirically supported treatments in pediatric psychology: constipation and
      encopresis.

PMID- 11516060
TI  - Differences in innate immunologic response to group B streptococcus between
      colonized and noncolonized women.
AB  - OBJECTIVE: To evaluate the functional capacity of granulocytes and monocytes from
      pregnant and nonpregnant women in relation to group B streptococcus (GBS)
      colonization status. METHODS: Engulfment of fluorescent GBS by peripheral blood
      phagocytes from GBS-colonized and noncolonized women was measured by flow
      cytometry. Intracellular superoxiode generated in response to GBS challenge to
      monocytes and granulocytes enriched from peripheral blood of these women was also
      measured by flow cytometry, and extracellular superoxide was determined by
      colorimetric assay. RESULTS: Monocytes and granulocytes from pregnant, GBS
      colonized women engulfed significantly greater numbers of GBS than phagocytes
      from pregnant, noncolonized women. No difference in intracellular superoxide
      production was detected between any of the groups of women; however, monocytes
      from pregnant, colonized women released significantly more superoxide into the
      extracellular milieu than did granulocytes from the same women. No differences in
      extracellular release of superoxide were observed among noncolonized women
      whether they were pregnant or not. CONCLUSIONS: Monocytes from pregnant,
      colonized women engulf more GBS and release more of the superoxide into the
      extracellular environment, where it is unlikely to be an effective defense
      mechanism against intracellular bacteria. This suggests that components of the
      innate immune system that should serve in a protective role may function
      suboptimally, thereby contributing to the colonization process by GBS.

PMID- 11516061
TI  - A multicenter study of bacterial vaginosis in women with or at risk for human
      immunodeficiency virus infection.
AB  - BACKGROUND: Bacterial vaginosis is a common gynecologic infection that has been
      associated with a variety of gynecologic and obstetric complications, including
      pelvic inflammatory disease, postabortal infection and premature delivery. Recent
      studies suggest that bacterial vaginosis may increase a woman's risk for human
      immunodeficiency virus (HIV). We undertook this study to assess whether the
      prevalence and characteristics of bacterial vaginosis differed according to HIV
      status in high-risk US women. METHODS: Prevalence of bacterial vaginosis was
      assessed by Gram's stain and clinical criteria for 854 HIV-infected and 434 HIV
      uninfected women enrolled in the HIV Epidemiology Research (HER) Study. Multiple
      logistic regression techniques were used to determine whether HIV infection
      independently predicted bacterial vaginosis. RESULTS: Almost half (46%) the women
      had bacterial vaginosis by Gram's stain. The prevalence of bacterial vaginosis
      was 47% in the HIV-positive women compared with 44% in the HIV-negative women;
      this difference was not statistically significant (p = 0.36). After adjustment
      for other covariates, HIV-positive women were more likely than HIV-negative women
      to have bacterial vaginosis (odds ratio (OR) 1.31; 95% confidence interval (CI)
      1.01-1.70) by Gram's stain but not by clinical criteria (OR 1.16; CI 0.87-1.55).
      Among HIV-positive women, use of antiretroviral drugs was associated with a lower
      prevalence of bacterial vaginosis (adjusted OR 0.54; Cl 0.38-0.77). CONCLUSIONS:
      In this cross-sectional analysis of high-risk US women, HIV infection was
      positively correlated with bacterial vaginosis diagnosed by Gram's stain.

PMID- 11516062
TI  - Prevalence of sexually transmitted infections (Neisseria gonorrhoeae, Chlamydia
      trachomatis, Trichomonas vaginalis and human papillomavirus) in female attendees
      of a sexually transmitted diseases clinic in Ulaanbaatar, Mongolia.
AB  - BACKGROUND: Epidemiological data suggest that the prevalence of syphilis,
      gonorrhea and trichomoniasis has increased in both urban and rural areas of
      Mongolia. These data are primarily substantiated by notifications of cases of
      clinically apparent disease in both rural and urban areas, plus laboratory
      diagnoses from the AIDS/STD Reference Center, Ulaanbaatar. In the past 5 years,
      however, there has been a marked decline in the total number of patients being
      screened for sexually transmitted infections (STIs). An assessment of true
      prevalence of STIs in a female population attending an urban sexually transmitted
      diseases (STD) clinic was therefore commenced. METHODS: Consecutive women
      attending an STD clinic in Ulaanbaatar had genital samples collected by the
      insertion and immediate removal of a tampon, which was then tested for the
      presence of Neisseria gonorrhoeae, Chlamydia trachomatis, human papillomavirus
      (HPV) and Trichomonas vaginalis, using polymerase chain reaction (PCR)
      amplification. RESULTS: A total of 110 women were studied (mean age 26.7 years).
      Overall, 58 (53%) patients had one or more pathogens identified; 43 (39%) had a
      single pathogen, while 15 (14%) had mixed pathogens. C. trachomatis was found in
      15 (14%), N. gonorrhoeae in 12 (11%), T. vaginalis in nine (8%) and HPV in 39
      (36%). Among the 39 HPV-positive patients, oncogenicgenotypes (16, 18, 31, 33,
      35, 39, 45, 51, 52) were found in 17(44%) patients. CONCLUSIONS: Sexually
      transmitted infections as defined by PCR were common, and found in 53% of female
      attendees of an urban STD clinic in Mongolia. As infections with conventional
      STIs increase the risk of human immunodeficiency virus (HIV) transmission, it is
      imperative that strategies be introduced to reduce the prevalence of STIs.
      Furthermore, detection of oncogenic HPV was common, indicating that it is vital
      that a strategy to reduce cervical cancer such as a pre-cancer cervical cytology
      screening program also be introduced.

PMID- 11516063
TI  - Candida sepsis following transcervical chorionic villi sampling.
AB  - BACKGROUND: The use of invasive devices and broad spectrum antibiotics has
      increased the rate of candidal superinfections. Candida sepsis associated with
      pregnancy is rare. Candida sepsis following chorionic villi sampling (CVS) has
      never been reported. CASE: A 31 -year-old pregnant woman presented with signs of
      sepsis one day after undergoing transcervical CVS. Blood culture and curettage
      material yielded C. albicans. She was treated with 400 mg of fluconazole daily
      for 4 weeks and completely recovered. CONCLUSION: Candida sepsis should be
      considered in the differential diagnosis of sepsis following CVS.

PMID- 11516065
TI  - A critical evaluation of the scientific basis of the MAK Commission's new general
      threshold limit values for dust.
AB  - In 1997, the German Commission for the Investigation of Health Hazards of
      Chemical Compounds in the Work Area set a new MAK value ("Maximale Arbeitsplatz
      Konzentration") governing worker exposures to general airborne dust. The new
      values limit worker dust exposures to concentrations not exceeding 1.5 mg/m3 for
      respirable dust and 4 mg/m3 for inhalable dust, and are substantially lower than
      corresponding standards in other western industrialized nations. The purpose of
      this document is to critically review the science behind the MAK Commission's new
      threshold limit value standards. The Commission relied heavily upon a re-analysis
      of data from the Deutsche Forschungsgemeinschaft (DFG) Chronic Bronchitis study
      (1965-1977). We have reservations about the scientific merit of the DFG study and
      the validity of data used as the basis for establishing a new MAK value for dust.
      In particular: (1) Assessing the potential role of inert dust in the development
      of chronic bronchitis in worker cohorts with extremely high cigarette smoking
      prevalences is scientifically implausible. (2) It is unlikely that the dust in
      the industries studied, including steel works, foundries and cement works, was in
      fact "inert", and any effects of the dust on chronic bronchitis rates may have
      been increased by the presence of free crystalline silica and other toxic agents.
      (3) The study made use of area- rather than personal-exposure monitoring, thereby
      correlating the prevalence of chronic bronchitis with lower dust exposure levels
      than actually existed and significantly overstating the health effects of the
      dust exposures. (4) Inappropriate statistical methods were used to estimate
      threshold limit values. Results of three additional epidemiological studies are
      cited as providing evidence of chronic lung effects due to insoluble dust
      exposure. All three studies suffer from extremely poor documentation of the study
      methodology, particularly regarding lung function testing, and they provide
      little evidence that exposure to insoluble non-fibrogenic dusts leads to chronic
      lung obstruction. In summary, it is our opinion that the studies evaluated by the
      MAK Commission and the methods used do not provide the scientific basis to
      support the lower threshold limit values for dust. We recommend that an
      appropriate prospective morbidity study be conducted to address the concerns
      detailed in this critical examination.

PMID- 11516064
TI  - Female genital warts: global trends and treatments.
AB  - The increasing incidence of human papillomavirus (HPV) infection and HPV
      associated conditions such as genital warts in women is a global concern. Genital
      warts are a clinical manifestation of HPV types 6 and 11, and are estimated to
      affect 1% of sexually active adults aged between 15 and 49. HPV infection is also
      strongly associated with cervical cancer, and is prevalent in as many as 99% of
      cases. The psychological stress of having genital warts is often greater than the
      morbidity of the disease, and therefore successful treatment is crucial. Current
      treatments are patient-applied and provider-administered therapies. Imiquimod 5%
      cream, a patient-applied therapy, is an efficacious treatment with tolerable side
      effects and a low recurrence rate, and has the potential to be an effective
      strategy for the management of genital warts.

PMID- 11516067
TI  - Interpretation of the finger skin temperature response to cold provocation.
AB  - OBJECTIVES: To compare alternative methods of interpreting the response of finger
      skin temperature (FST) to cold provocation for the detection of the abnormal cold
      response observed in vibration-induced white finger (VWF). METHOD: The FST
      response to cold provocation was measured in 36 male subjects: 12 office workers,
      12 manual workers and 12 manual workers with symptoms of VWF. The FSTs were
      monitored continuously on the distal phalanges of all five fingers of a test hand
      for 2 min before, for 5 min during, and for 10 min following, immersion of the
      test hand in water at 15 degrees C. Of the fingers investigated, 147 were
      reported not to exhibit blanching and 33 were reported to exhibit blanching.
      Twenty-one alternative methods of interpreting the response of FSTs to cold
      provocation were assessed. These were grouped as: (1) areas above the response
      profile (i.e. the area above the curve showing the FSTs as a function of time
      during cooling and recovery), (2) areas below the response profile, (3) absolute
      temperatures during and following cold provocation, (4) percentage differences in
      FSTs, (5) the times taken for FSTs to rise by specified amounts and (6) rates of
      change of FSTs. Differences in the response to cooling between those fingers
      reported to blanch and the fingers not reported to blanch were tested, and
      receiver operating characteristics (ROCs) were used to compare the sensitivity
      and specificity of the various measures to symptoms of VWF. RESULTS: The areas
      above the response profile, areas below the response profile, percentage FSTs,
      absolute FSTs and rates of change of FSTs tended to discriminate between healthy
      and unhealthy subjects on a group basis. However, some of these methods of
      interpreting the FST response to cold provocation did not show a high sensitivity
      or specificity to vascular dysfunction on individual fingers. The area above the
      response profile, the percentage of initial temperature at the fifth minute of
      recovery and the maximum temperature during the 10-min recovery period, were
      found to show the highest sensitivity and specificity to symptoms of vascular
      dysfunction. CONCLUSIONS: The method chosen to interpret the FST response to cold
      provocation affects the ability of the test to detect an abnormal cold response.
      The area above the response profile, the percentage of initial temperature at the
      fifth minute of recovery and the maximum temperature achieved during a 10-min
      recovery period appear to be the most suitable measures for monitoring vascular
      function in workers exposed to hand-transmitted vibration. It is suggested that
      the FST response to cold provocation should be interpreted with respect to the
      state of initial blood flow.

PMID- 11516066
TI  - Changes in low molecular weight DNA fragmentation in white blood cells of workers
      highly exposed to asbestos.
AB  - OBJECTIVE: The aim of this study was to determine low molecular weight (LMW)-DNA
      fragmentation changes after white blood cell (WBC) incubation in lysis buffer
      followed by constant-field gel electrophoresis (CFGE). WBCs were isolated from
      blood samples of workers highly exposed to asbestos fibres at the workplace in
      Germany, and were compared with those from healthy adults. This study was
      conducted parallel to the study presented in our preceding paper (Marczynski et
      al. 2000b) in which we described significant increases in the levels of 8-hydroxy
      2'-deoxyguanosine (8-OHdG) adducts in the DNA of white blood cells from the same
      highly exposed workers relative to the levels found in the control group in all
      three study years (1994 to 1997). METHOD: We found that 15-h incubation in lysis
      buffer of WBCs embedded in agarose-plugs from healthy control donors with 2% SDS,
      proteinase K and Na2-EDTA at 42 degrees C followed by 0.5 h at 4 degrees C
      produced a characteristic DNA fragmentation pattern below 23 kbp using CFGE.
      RESULTS: In the 1st year of the study (1994-1995) changes were found in LMW-DNA
      fragmentation in 54.8% of the asbestos workers studied, compared with the DNA
      fragmentation pattern of controls. Interestingly, in the 2nd year of the study
      (1995 1996) changes in DNA fragmentation were found in only 39.9% of exposed
      subjects. In the 3rd year of the study (1996-1997) the highest number of workers
      exposed to asbestos (67.3%) with changes in the LMW-DNA fragmentation pattern was
      found. The Chi-square test for each year of the study revealed significant
      changes (P < 0.001). These changes may be due to the presence of hydrogen
      peroxide (H2O2), as has been shown in vitro. It is likely that a Fenton reaction
      involving the heterolytic reduction of H2O2 by traces of reduced transition
      metals such as Fe2+ and Cu+ is involved in the fragmentation of DNA. No
      difference was found in the changes in DNA fragmentation between asbestos-exposed
      subjects with and without benign asbestos-associated diseases (asbestosis,
      asbestos-associated pleural plaques). Significant correlations were not found
      after analysis of the changes in DNA fragmentation in relation to different
      possible occupational and non-occupational confounding factors, such as the
      duration of asbestos exposure, the latency period, estimated cumulative fibrous
      dust dose ("fibre-years"), and non-occupational confounding factors, such as age,
      smoking status, acute febrile infections, the intake of medicines, aspirin, Ca2+,
      Mg2+ and/or hormones, the intake of vitamins, and cases of cancer. CONCLUSIONS:
      Our data confirm that oxidative stress occurs in the WBCs of workers highly
      exposed to asbestos fibres, thus supporting the hypothesis that asbestos fibres
      damage cells through an oxidative mechanism. Oxidative stress and oxidative DNA
      damage may be induced by long-term exposure to asbestos. The new insights into
      the oxidative effects of asbestos fibres are of great importance because they
      provide a way forward for new preventive strategies. Preventive and therapeutic
      approaches using antioxidants should be taken into consideration.

PMID- 11516068
TI  - Inter- and intra-individual sources of variation in levels of urinary styrene
      metabolites.
AB  - OBJECTIVE: Given the paucity of studies that have examined variability in
      biological measures of exposure to workplace contaminants, we quantified the
      intra- and inter-individual sources of variation in urinary levels of mandelic
      acid (MA) and phenylglyoxylic acid (PGA) among workers exposed to styrene. A
      secondary objective was to examine effects of job task and the timing of sampling
      during the workweek on the variation in workers' urinary styrene metabolite
      levels. METHODS: As part of routine biological monitoring, a total of 1,714
      measurements of MA and PGA collected from 331 workers between 1985 and 1999 from
      eight reinforced-plastics plants were abstracted from laboratory reports. To
      evaluate sources of variation in levels of urinary styrene metabolites, we
      applied random-effects models. The influence of job task and day of sampling on
      metabolite levels was examined using mixed-effects models. RESULTS: PGA levels
      were characterized by less variation than levels of MA, as were metabolite levels
      expressed in terms of urinary creatinine concentration. The relative magnitude of
      the inter-individual to the intra-individual source of variation was generally
      higher for post-shift urine samples than for pre-shift urine samples. As
      expected, urinary metabolite levels were highest for laminators and for samples
      collected at the latter end of the workweek. Owing to the effects of variation
      from day-to-day, estimates of workers' exposures that rely on single measurements
      would generally perform poorly in a regression analysis designed to examine
      effects resulting from chronic exposure. However, the bias in an observed slope
      coefficient would be diminished if a second or third urine sample were collected.
      CONCLUSIONS: Quantification of the intra- and inter-individual sources of
      variation provides useful information that can be used to design optimal sampling
      strategies, which would allow for the collection of sufficient data to estimate
      workers' exposures reliably when evaluating health risks associated with
      occupational contaminants.

PMID- 11516069
TI  - The development of a new method to estimate total daily dose of pesticides in
      professional turf applicators following multiple and varied exposures in
      occupational settings.
AB  - The evaluation of absorbed dose of pesticides in humans requires a knowledge of
      the kinetics and dynamics of the compound. In some circumstances, data that allow
      for the estimation of dose may be available from human volunteer studies,
      although often, it will be based on results from animal studies. If human
      metabolism data are available, estimates of dose may be more accurate, but it
      should be recognized that pesticide exposure in an occupational setting may
      differ from that in a controlled laboratory study. In this study, data from
      previously published studies are used to evaluate the urinary excretion of 2,4
      dichlorophenoxyacetic acid (2,4-D), following single dermal applications to human
      volunteers. These studies are evaluated with the objective of determining the
      best method of predicting total absorbed dose following multiple and varied
      exposures in occupational settings. Further, an alternative to laboratory
      controlled human volunteer studies is presented. Data from a third previously
      published biological monitoring study on six professional pesticide applicators
      over a 2-week period were used to generate estimates of the urinary excretion of
      the pesticide 2,4-D that would result from a single dose. The method used to
      estimate the urinary excretion parameters is a variation of an overlay technique
      used in pharmacology, and may provide information on the kinetics of other
      pesticides when it is not possible to conduct human studies. The generated
      estimates of 24-h urinary excretion of 2,4-D over a 6-day period were remarkably
      similar to those obtained in controlled studies. Finally, a method was developed
      to use the generated estimates to determine total absorbed dose of pesticides for
      an independent group of 95 professional pesticide applicators. This method
      requires information on the amount of pesticide used for 6 days prior to the
      collection of two, 24-h urine samples.

PMID- 11516070
TI  - Stereochemical metabolism of styrene in volunteers.
AB  - OBJECTIVES: To study the stereochemistry of styrene metabolism in volunteers, and
      its interindividual variability. METHODS: Twenty healthy male volunteers (aged 18
      37 years) were exposed to 360 mg/m3 styrene for 1 h while they performed 50 W
      physical exercise. Venous blood was drawn during and for up to 2 h after
      exposure. Urine was collected at time-intervals up to 24 h after exposure. The
      following parameters were determined: styrene, free and conjugated styrene glycol
      (SG) in blood, and conjugated SG, mandelic acid (MA) and phenylglyoxylic acid
      (PGA) in urine. RESULTS: Average pulmonary retention of styrene was 62%.
      Excretion of the acidic metabolites MA and PGA accounted for 58% of the pulmonary
      uptake. The average maximum concentration (Cmax) and area under the curve (AUC)
      of free (R)-SG in blood were 1.3 and 1.7 times higher than those of (S)-SG
      respectively; the half-life of (R)-SG was longer (82 vs 62 min, P < 0.005). Cmax
      and AUC of the conjugated SG enantiomers in blood did not differ, but again half
      life for (R)-SG was longer (72 vs 64 min, P < 0.05). Cumulative excretion and
      renal clearance of conjugated (S)-SG in urine were three and four times higher,
      respectively, than that of (R)-SG. Cumulative excretion of (S)-MA was 1.6 times
      higher than (R)-MA. Interindividual differences in the kinetic parameters of the
      metabolites were two- to threefold. CONCLUSIONS: The enantiomeric excess found
      was different for each metabolite under study, implying different
      enantioselectivity and/or enantiospecificity of the enzymes and carrier-proteins
      involved in the biotransformation and excretion. The use of these metabolites as
      biological indicators for prediction of the enantiomeric excess of the toxic
      metabolite styrene-7,8-oxide (SO) is therefore not justified. Interindividual
      differences in the stereochemical metabolism of styrene are moderate.

PMID- 11516071
TI  - Effects of sedentary work on physical fitness and serum cholesterol profile in
      middle-aged male workers.
AB  - OBJECTIVES: To evaluate independent and interactive health effects of physical
      activity at work (PAW) and physical activity at habitual exercise (PAHE).
      METHODS: A cross-sectional study on 1,117 male workers aged 29 to 46 years with a
      mean of 37.0 years. Using a self-administered questionnaire, the subjects were
      classified into 'High'/'Low' (n = 338/779) on PAW, and into 'Yes'/'No' (n =
      353/764) on PAHE. As outcome indices, physical fitness expressed as maximal
      oxygen uptake (VO2max) was estimated, and serum total cholesterol (TC), HDL
      cholesterol (HDLC) and TC/HDLC ratio were determined. Age, body mass index
      (kg/m2), alcohol-drinking and smoking were used as confounding factors. RESULTS:
      The 'High' PAW group had a significantly higher level of VO2max than the 'Low'
      PAW group (+ 1.0 ml/kg min; 34.4 vs. 33.4 ml/ kg min in adjusted means). The
      'High' PAW group also had a better profile of serum cholesterol than the 'Low'
      PAW group, but it was not significant. The 'Yes' PAHE group had significantly
      higher levels of VO2max (+ 2.0 ml/kg min; 34.9 vs. 32.9 ml/kg min) and serum HDLC
      (+0.09 mmol/l; 1.48 vs. 1.39 mmol/l), and a significantly lower TC/HDLC ratio (
      0.29; 3.90 vs. 4.19) than the 'No' PAHE group. Among PAW PAHE subgroups, the
      'High-Yes' group (n = 110), most physically active, had the best profile of
      VO2max and serum cholesterol, and the 'Low-No' group (n = 536), least physically
      active, had the worst one. Interactive effects of PAW and PAHE were not found
      either on VO2max or on serum cholesterol profile. All the results were not
      influenced by statistical adjustments for the four confounding factors used here.
      CONCLUSIONS: Both sedentary work and lack of habitual exercise are very common in
      Japanese workers. Sedentary work, independently from lack of habitual exercise,
      may increase the risk of diseases related to physical inactivity by affecting
      physical fitness and serum cholesterol profile.

PMID- 11516072
TI  - Symptoms and serum precipitins in workers exposed to dry sausage mould:
      consequences of exposure to sausage mould.
AB  - OBJECTIVE: Hypersensitivity pneumonitis due to dry sausage mould has been
      reported in workers who brush off the excess mould which coats dry sausage.
      Prevalence of symptoms and sensitization to mould among these pork-butchery
      workers is unknown. The aim of the study was to assess the clinical,
      radiographic, functional, and immunological features in exposed and non-exposed
      workers in semi-industrial pork butcheries. PATIENTS AND METHODS: Symptoms, and
      serum precipitins against mould extracts, were studied in workers in semi
      industrial pork butcheries. Of 600 workers asked to participate, 123 (20.5%) were
      included. Fifty-nine workers, exposed to dry (raw) sausage mould and Penicillium
      nalgiovense were compared with 64 non-exposed subjects, for symptoms, chest X
      rays, spirometry and CO-transfer measurements. Precipitating antibodies were
      detected by immunoelectrophoresis and electrosyneresis. RESULTS: Sneezing, cough,
      dyspnoea, nasal obstruction, headache, and discomfort were significantly more
      frequent in the exposed group at work and after work than in the control group (P
      < 0.05). The prevalence of precipitating antibodies for sausage mould was higher
      in the exposed group (37%) than in the non-exposed group (9%) (P < 0.01). The
      mean number of precipitating lines measured by electrosyneresis was higher in
      exposed workers than in non-exposed workers for mould extract (1.09 vs 0.28, P <
      0.05) and for Penicillium nalgiovense (1.77 vs 0.33, P < 0.05). No specific X-ray
      opacity or lung function impairment was found in either group. CONCLUSIONS:
      Clinical symptoms and sensitization to Penicillium nalgiovense are frequent among
      workers exposed to mould during brushing in dry sausage plants.

PMID- 11516073
TI  - Association between blood levels of lead, blood pressure and risk of diabetes and
      heart disease in workers.
AB  - BACKGROUND: Previous studies have supported the association between high levels
      of blood lead levels (BLL) and elevated blood pressure. In addition, significant
      correlations between BLL and a variety of risk factors for blood pressure and
      diabetes mellitus have been well-established. OBJECTIVE: To examine the
      relationship between BLL, blood pressure and diabetes as well as other selected
      social and biochemical factors, among workers in the United Arab Emirates (UAE).
      METHODS: This comparative study included 110 industrial workers (exposed to lead
      in the workplace) and 110 non-industrial workers (not exposed); all were
      recruited in the city of Al-Ain, Abu-Dhabi Emirate, UAE and the groups were
      evenly matched for age, gender and nationality. RESULTS: The industrial workers
      had a significantly higher mean of BLL (median 81 and geometric mean (GM) 62
      microg/dl) than did non-industrial workers (median 11 and GM 13 microg/dl). In
      the present study, the lead-exposed group also had significantly higher blood
      lead levels, body-mass index (BMI), systolic and diastolic blood pressures,
      fasting blood glucose and plasma levels of total cholesterol, lactate
      dehydrogenase and uric acid than did the non-exposed group. Furthermore a
      significant correlation between BLL and systolic blood pressure was observed.
      CONCLUSION: The study supports the hypothesis of a positive association between
      lead exposure, high blood pressure and risk of diabetes and heart disease.

PMID- 11516074
TI  - Laser cutting: influence on morphological and physicochemical properties of
      polyhydroxybutyrate.
AB  - Polyhydroxybutyrate (PHB) is a biocompatible and resorbable implant material. For
      these reasons, it has been used for the fabrication of temporary stents, bone
      plates, nails and screws (Peng et al. Biomaterials 1996;17:685). In some cases,
      the brittle mechanical properties of PHB homopolymer limit its application. A
      typical plasticizer, triethylcitrate (TEC), was used to overcome such limitations
      by making the material more pliable. In the past few years, CO2-laser cutting of
      PHB was used in the manufacturing of small medical devices such as stents.
      Embrittlement of plasticized PHB tubes has been observed, after laser machining.
      Consequently, the physicochemical and morphological properties of laser-processed
      surfaces and cut edges of plasticized polymer samples were examined to determine
      the extent of changes in polymer properties as a result of laser machining. These
      studies included determination of the depth of the laser-induced heat affected
      zone by polariscopy of thin polymer sections. Molecular weight changes and
      changes in the TEC content as a function of distance from the laser-cut edge were
      determined. In a preliminary test, the cellular response to the processed
      material was investigated by cell culture study of L929 mouse fibroblasts on
      laser-machined surfaces. The heat-affected zone was readily classified into four
      different regions with a total depth of about 60 to 100 microm (Klamp, Master
      Thesis, University of Rostock, 1998). These results correspond well with the
      chemical analysis and molecular weight measurements. Furthermore, it was found
      that cells grew preferentially on the laser-machined area. These findings have
      significant implications for the manufacture of medical implants from PHB by
      laser machining.

PMID- 11516075
TI  - Gradient micropattern immobilization of EGF to investigate the effect of
      artificial juxtacrine stimulation.
AB  - To investigate the concentration effects of immobilized biosignal molecules by
      microscopic observation, a gradient micropattern immobilization technique using a
      photomask was devised. Epidermal growth factor (EGF) was chosen as the biosignal
      molecule and was conjugated with photoreactive polyallylamine. The EGF derivative
      was immobilized onto a polystyrene plate by UV irradiation in the presence of a
      gradient-micropattern photomask. Gradient micropattern immobilization of the EGF
      derivative on the polystyrene plate was confirmed by immunostaining with anti-EGF
      antibody. Chinese hamster ovary cells overexpressing EGF receptors were cultured
      on the micropatterned plate. Growth enhancement was observed only in dense EGF
      derivative immobilized regions. The present technique is useful for the
      investigation of concentration-dependent effects of immobilized biosignal
      molecules.

PMID- 11516076
TI  - Affinity binding phenomena of DNA onto apatite crystals.
AB  - The effect of DNA on the crystal growth of hydroxyapatite (HAp) and its
      morphology was examined. X-ray diffraction patterns of DNA-containing apatites
      showed typical apatitic features. However, crystal growth was greatly inhibited
      in the presence of DNA during synthesis; particularly, the crystallinity in the a
      axis direction decreased dramatically at low concentrations of DNA. The a- and c
      axis dimensions of each precipitate were almost the same, which implies that DNA
      molecules affect only the crystal surface. CHN analysis clearly showed the
      presence of these elements, which increased with an increase in DNA concentration
      in the solution. Scanning electron micrographs of the precipitates formed in the
      presence of DNA showed typical needle-like crystals, with a decreased crystal
      size, especially width. Infrared absorption spectroscopy of the DNA-containing
      apatites showed that the 1630-1700 cm(-1) absorption band due to C=C and C=N
      stretching increased with an increase in DNA concentration during precipitation.
      The ESCA spectrum of HAp(DNA 1.0) shows N 1s and C 1s peaks that are absent and
      weak, respectively in HAp. 31P NMR spectroscopy revealed a weak peak at the base
      of the 31P peak from the PO4(3-) ions in the HAp crystals. This weak 31P peak had
      a small positive shift from the position found in native DNA which may be due to
      the phosphate backbone of adsorbed DNA. The apparent solubility of the HAps
      increased with an increase in DNA concentration. These results suggest that there
      is an affinity binding between apatite crystal and DNA molecules.

PMID- 11516077
TI  - Grooves affect primary bone marrow but not osteoblastic MC3T3-E1 cell cultures.
AB  - To elucidate the influence of microtextures on bone cell performance, primary
      adult rat bone marrow cells (RBMC) and osteoblastic MC3T3-E1 cells were cultured
      on tissue culture pretreated plates to which grooves at different density were
      applied. RBMC cells were found to be significantly affected by grooves in the
      substratum in contrast to osteoblastic MC3T3-E1 cells, taking culture morphology,
      total cell number, cell mass, and cell activity (MTT-dehydrogenase), parameter
      for differentiation of osteoblast progenitor cells into (pre-)osteoblasts
      (alkalinephosphatase activity, ALP) and tartrate-resistant acid phosphatase
      (TRAP) activity as indices. TRAP is located in lysosomes and secretory granules
      mainly although not solely in osteoclasts. By applying grooves to and/or by
      chemical treatment of unpretreated pure polysterene plates it could be concluded
      that the effects on RBMC cells were evoked not only by the presence of grooves
      but also by the surface chemistry of the grooved and ungrooved surface areas.

PMID- 11516078
TI  - Effect of nickel-titanium shape memory metal alloy on bone formation.
AB  - The aim of this study was to determine the biocompatibility of NiTi alloy on bone
      formation in vivo. For this purpose we used ectopic bone formation assay which
      goes through all the events of bone formation and calcification. Comparisons were
      made between Nitinol (NiTi), stainless steel (Stst) and titanium-aluminium (6%)
      vanadium (4%) alloy (Ti-6Al-4V), which were implanted for 8 weeks under the
      fascia of the latissimus dorsi muscle in 3-month-old rats. A light-microscopic
      examination showed no chronic inflammatory or other pathological findings in the
      induced ossicle or its capsule. New bone replaced part of the decalcified matrix
      with mineralized new cartilage and bone. The mineral density was measured with
      peripheral quantitative computed tomography (pQCT). The total bone mineral
      density (BMD) values were nearly equal between the control and the NiTi samples,
      the Stst samples and the Ti-6Al-4V samples had lower BMDs. Digital image analysis
      was used to measure the combined area of new fibrotic tissue and original
      implanted bone matrix powder around the implants. There were no significant
      differences between the implanted materials, although Ti-6Al-4V showed the
      largest matrix powder areas. The same method was used for measurements of
      proportional cartilage and new bone areas in the ossicles. NiTi showed the
      largest cartilage area (p < or = 0.05). Between implant groups the new bone area
      was largest in NiTi. We conclude that NiTi has good biocompatibility, as its
      effects on ectopic bone formation are similar to those of Stst, and that the
      ectopic bone formation assay developed here can be used for biocompatibility
      studies.

PMID- 11516079
TI  - Association of vancomycin and calcium phosphate by dynamic compaction: in vitro
      characterization and microbiological activity.
AB  - Dynamic compaction has rarely been used to produce drug-delivery devices in
      granule form. This report considered four processes associating vancomycin and
      compared dynamic compaction with wet granulation, a classical method. In the wet
      granulation study, vancomycin was associated with biphasic calcium-phosphate
      (BCP) granules either by adsorption or incorporation with a new granulation. In
      the dynamic compaction study, BCP powder was compacted at 1.1, 1.5 and 1.9 MPa.
      The compacts obtained were crushed and sieved (200-500 microm), and the
      vancomycin solution was adsorbed on the resulting granules. After crushing and
      sieving, the compaction of BCP and vancomycin powders produced vancomycin-loaded
      granules. In each study, 4.76% of vancomycin was associated with BCP. Granules
      were characterized in terms of porosity, vancomycin release and vancomycin
      biological activity. Physicochemical studies of BCP and vancomycin showed their
      structural integrity after dynamic compaction, which prolonged vancomycin release
      time from 1 to 6 days. However, a microbiological assay indicated that vancomycin
      had been altered since only 27.7% was found to be active.

PMID- 11516080
TI  - Biomimetic apatite formation on polyethylene photografted with
      vinyltrimethoxysilane and hydrolyzed.
AB  - A photografting technique to produce functional groups of silanol able to induce
      apatite nucleation was attempted on polyethylene substrate for biomimetic
      formation of bone-mineral-like apatite layer on its surface. The polyethylene
      surface was subjected to vapor-phase photografting of vinyltrimethoxysilane and
      subsequently to hydrolysis. The photografting formed methoxysilyl groups on the
      polyethylene substrate, which was changed into silanol groups successively by the
      hydrolysis in a hydrochloric solution. The polyethylene modified in this way
      formed a dense and homogeneous bone-mineral-like apatite layer in a solution with
      ion concentrations 1.5 times that of human blood plasma. This result indicates
      that the biomimetic process in combination with a polymeric grafting technique
      might provide a homogeneous bone-mineral-like apatite coating even on polymer
      fibers to be woven into an apatite-polymer composite with three-dimensional
      structure analogous to that of natural bone.

PMID- 11516081
TI  - Polymeric microspheres composed of pH/temperature-sensitive polymer complex.
AB  - A new pH/temperature-sensitive polymer system with transitions resulting both
      from polymer-water and polymer-polymer interactions has been demonstrated using
      the mixture of poly(N,N-dimethylamino)ethyl methacrylate (DMAEMA) and polyethyl
      acrylamide (EAAm). Based on the pH/temperature sensitivity of polymer mixture,
      the microsphere for pH/temperature-sensitive drug release have been designed and
      characterized. Hydrocortisone was used as a model drug. This gave the control of
      hydrocortisone release in an on-off manner without considerable lag time.

PMID- 11516082
TI  - High reactivity of alkyl sulfides towards epoxides under conditions of collagen
      fixation--a convenient approach to 2-amino-4-butyrolactones.
AB  - Epoxy crosslinking agents have been investigated for use in the fabrication of
      bioprosthetic devices, such as heterograft heart valve prostheses. It has been
      generally assumed that epoxy crosslinking takes place via amino-epoxy reactions.
      The present study investigated the hypothesis that the reactions of methionine
      residues with epoxides also can occur in biomaterial crosslinking. A series of
      model reactions were studied in which a mono-epoxide was combined with individual
      alkyl sulfides. In the present studies epoxides rapidly alkylate aliphatic
      sulfides, including methionine derivatives, in buffered aqueous solutions at room
      temperature and pH close to neutral, forming sulfonium compounds, which are
      stable at pH 5-7 at temperatures up to 50 degrees C, except for cases in which
      methionine derivatives with non-protected carboxy groups are used. The rate of
      reaction remains practically unchanged within the range of pH from 5 to 12,
      whereas in strongly alkaline media the reverse reaction occurs. This discovery
      can provide a better understanding of processes occurring in the fixation of
      bioprosthetic tissues with polyepoxides. It can also develop into a site-specific
      method to label methionine residues in proteins. The carboxy group-containing
      sulfonium betaines derived from N-protected methionines undergo cyclization in
      unexpectedly mild conditions, which can be used as an efficient method for
      preparation of N-protected 2-amino-4-butyrolactones with sensitive protective
      groups.

PMID- 11516083
TI  - Kinetics of fluoride release from zinc oxide-based cements.
AB  - Considerable attention has been given to the release of the cariostatic fluoride
      ion from glass-based dental cements (dental silicate and glass ionomer). In
      these, the total available fluoride content is not precisely known since fluorine
      is distributed between the cross-linked aqueous salt matrix, partially dissolved
      glass, and undissolved glass. In analogous cements based on zinc oxide the
      fluoride is added as highly soluble SnF2. The object of this study is to compare
      the F- ion release profiles of commercial zinc polycarboxylate and zinc phosphate
      containing 4.4 and 3.6% SnF2, respectively. Mixed cements were clamped in split
      ring moulds to produce discs of 10 mm x 1 mm after storage at 37 degrees C for 1
      h. Each was weighed and immersed in 10 ml of deionised water. When this changed,
      at 13 time intervals up to 98 days, the fluoride content was measured using an
      ion selective electrode. The mean (N = 3) values obtained were expressed
      cumulatively [F] in micromol F ion/g cement. The total [F] released was 111 for
      the zinc polycarboxylate and 286 for zinc phosphate compared with total F in the
      cements of 561 and 464, respectively. When the cumulative [F] was plotted versus
      t(1/2) close associations were found for both cements. For the polycarboxylate
      the regression line [F] = 10.6t(1/2) + 9.9 fitted well over the whole 98 days (R
      = 0.997). For the phosphate a better fit regression line was obtained using
      results up to 32 days only; [F] = 36.8t(1/2) - 8.4 (R = 0.999). For t > 32 days
      results increasingly deviated from this line. These results fitted a regression
      line of the form [F] = 81.7log(e) t - 87.3 (R = 0.9997). Comparisons are made
      with data from previous authors both for zinc phosphate cement and glass-based
      cements and with diffusion theory of F ion release. It is concluded that zinc
      based cements provide some indications of how glass-based cements may behave over
      long periods of release and that zinc phosphate is the material of clinical
      choice for orthodontic cementation if maximal fluoride release is the prime
      criterion.

PMID- 11516084
TI  - Application of double-impedance system and cyclic voltammetry to study the
      adsorption of fullerols (C60(OH)n) on biological peptide-adsorbed gold electrode.
AB  - The adsorption of fullerols (C60(OH)n) on glutathione-adsorbed gold electrode was
      characterized by using double-impedance system, i.e., electrochemical quartz
      crystal impedance and electrochemical impedance spectroscopy, and cyclic
      voltammetry. The time courses of piezoelectric parameters were used to reflect
      the changes of interfacial physical properties, such as mass, density-viscosity,
      and dielectric constant, during the adsorptions of peptide and fullerols onto
      electrode. The electrochemical impedance based on the simple equivalent electric
      network were also simultaneously measured and provided electrochemical interface
      information, e.g., double-layer capacitance and charge-transfer resistance. It
      was found that the double-impedance responses were varied with the forms of
      glutathione. It was also shown that the frequency curves due to the adsorption of
      oxidized (GSSG) and reduced (GSH) glutathione could be exhibited as different
      kinetic equations. The heterogeneous charge-transfer rate constants of
      ferricyanide/ferrocyanide before and after the peptide and fullerols adsorption
      were determined by CV and EIS methods. The results showed that the proposed
      method has potential applications in interfacial studies of biomaterials, since
      these combined techniques have advantages in real time providing multidimensional
      piezoelectric and electrochemical impedance information.

PMID- 11516085
TI  - Titanium metals form direct bonding to bone after alkali and heat treatments.
AB  - In this article we evaluated the bone-bonding strengths of titanium and titanium
      alloy implants with and without alkali and heat treatments using the conventional
      canine femur push-out model. Four kinds of smooth cylindrical implants, made of
      pure titanium or three titanium alloys, were prepared with and without alkali and
      heat treatments. The implants were inserted hemitranscortically into canine
      femora. The bone-bonding shear strengths of the implants were measured using push
      out test. At 4 weeks all types of the alkali- and heat-treated implants showed
      significantly higher bonding strength (2.4-4.5 MPa) than their untreated
      counterparts (0.3-0.6 MPa). At 12 weeks the bonding strengths of the treated
      implants showed no further increase, while those of the untreated implants had
      increased to 0.6-1.2MPa. Histologically, alkali- and heat-treated implants showed
      direct bonding to bony tissue without intervening fibrous tissue. On the other
      hand, untreated implants usually had intervening fibrous tissue at the interface
      between bone and the implant. The early and strong bonding to bone of alkali- and
      heat-treated titanium and its alloys without intervening fibrous tissue may be
      useful in establishing cementless stable fixation of orthopedic implants.

PMID- 11516086
TI  - Biological glass coating on ceramic materials: in vitro evaluation using primary
      osteoblast cultures from healthy and osteopenic rat bone.
AB  - ZrO2 and Al2O3 substrates were successfully coated by a double layer of a silica
      based glass named RKKP, using a low-cost firing technique. RKKP is a glass well
      known for its bioactivity; therefore, a RKKP coating on Al2O3 or ZrO2, allows to
      combine the excellent mechanical properties of these strong ceramic substrates
      with its bioactivity. ZrO2 samples were easily coated using a double layer of
      RKKP by a simple enamelling technique. To accommodate the thermal expansion
      coefficient mismatch between Al2O3 and RK K P, this substrate was coated using a
      multilayered composite approach. All of the coatings were characterised from a
      morphological and compositional point of view, and an extensive biological
      evaluation was performed using fresh rat osteoblasts. Osteoblast primary cultures
      were derived from the trabecular bone of femoral condyles harvested from intact
      (NB) and osteopenic (OB) rats. After characterisation of their phenotype,
      osteoblasts were seeded on material samples of ZrO2 or Al2O3 coated with RKKP,
      and cultured for 7 days. Cell proliferation (MTT test) and cell differentiation
      (alkaline phosphatase activity) were evaluated at the end of the experiment, to
      assess osteoblast behaviour in the presence of biomaterials and determine if the
      results were related to the host bone quality. Results of both materials showed a
      good level of biocompatibility. In particular, MTT significant higher values were
      detected in NB cultures on ZrO2-RKKP samples; ALP activity significantly
      increased in NB cultures on Al2O3-RKKP and in OB cultures on both coated samples.

PMID- 11516087
TI  - Protein characterisation of salivary and plasma biofilms formed in vitro on non
      corroded and corroded dental ceramic materials.
AB  - Dental ceramics are generally regarded as low-adhesive materials. Different
      ceramics may, however, differ in composition and physico-chemical surface
      properties, which may be changed after corrosion. The aim of this study was to
      examine the adsorption of proteins onto specimens of different ceramic materials
      after the incubation in saliva and plasma before and after in vitro corrosion. In
      addition, the topography of the biofilm was examined by AFM. Surface-bound
      proteins were desorbed and analysed by polyacrylamide gel electrophoresis (PAGE)
      and immunoblotting using antibodies to saliva and plasma proteins. Silver-stained
      gels indicated differences in the adsorption of proteins. Differences in surface
      roughness at the nanometer level did not, however, seem to be correlated to the
      protein adsorption. After corrosion, unchanged or increased protein staining was
      generally seen in the gels and Western blots. The reactions for salivary amylase
      and proline-rich proteins varied between the different materials. Albumin and
      fibrinogen were identified in samples from all materials tested. Fibronectin and
      in specific IgA were more sparsely seen. No saliva but all plasma proteins were
      identified in the alumina and yttria-stabilised zirconia samples and reduced
      protein reactions were obtained after corrosion.

PMID- 11516088
TI  - Shear-load carrying capacity of cancellous bone after implantation of self
      reinforced polyglycolic acid and poly-L-lactic acid pins: experimental study on
      rats.
AB  - Both distal femora of 40 rats were implanted with a self-reinforced polyglycolic
      acid (SR-PGA) pin in the right femur and with a self-reinforced poly-L-lactic
      acid (SR-PLLA) pin in the left femur. The intact femora of 20 rats served as
      controls. The follow-up times were 1, 3, 6, 12, 24, 36, 48, and 52 weeks. After
      killing all operated and control femora were examined macroscopically and
      radiographically. The shear-load carrying capacities of all the femurs were
      investigated, and the SR-PGA and SR-PLLA fixed specimens were compared with each
      other and with the control specimens. The shear-load carrying capacities reached
      their highest values at 36 weeks in the SR-PGA and SR-PLLA fixed and control
      specimens. Thereafter they gradually decreased. At 52 weeks both the SR-PGA fixed
      specimens and the control specimens had statistically significantly (p < 0.001)
      higher values than the SR-PLLA fixed specimens, when the influence of the pins
      had ceased. Otherwise, the shear-load capacities showed higher values in the SR
      PLLA fixed specimens, as the pins carried the load. During the whole follow-up
      period the mean shear-load carrying capacity of the SR-PGA fixed specimens was
      171.2 N and that of the SR-PLLA fixed specimens 180.9 N, the corresponding value
      of the control specimens was 148.2 N.

PMID- 11516089
TI  - Preparation of poly(L-lactic acid) and poly(DL-lactic-co-glycolic acid) foams by
      use of ice microparticulates.
AB  - Biodegradable foams of poly(L-lactic acid) (PLLA) and poly(DL-lactic-co-glycolic
      acid) (PLGA) for tissue engineering were fabricated by a porogen-leaching
      technique using ice microparticulates as the porogen material. PLLA or PLGA
      solution in chloroform was mixed with ice microparticulates. The mixtures were
      frozen by being placed in molds in liquid nitrogen and freeze-dried to form the
      foams. Scanning electron microscopic observation of the PLLA and PLGA foams
      showed that evenly distributed and interconnected pore structures were formed in
      these foams. The porosity and surface area of the foams increased with an
      increase in the weight fraction of the ice microparticulates, while the median
      pore size remained unchanged. The pore structures of the foams could be
      manipulated by controlling processing variables such as the size and weight
      fraction of the ice microparticulates and polymer concentration.

PMID- 11516090
TI  - Culture of cells gained from temporomandibular joint cartilage on non-absorbable
      scaffolds.
AB  - The objective of this study was to investigate the adhesion, spreading and
      extracellular matrix synthesis of temporomandibular joint (TMJ) derived cells on
      non-absorbable scaffold materials to ultimately provide a durable stress
      absorbent framework within tissue-engineered disc transplants. Scaffolds were
      prepared by polyamide monofilaments, expanded polytetrafluoroethylene (ePTFE)
      monofilaments, polyglycolic acid monofilaments (control) or natural bone mineral
      blocks (control). These scaffolds were incubated for 2, 4 and 8 weeks under
      common culture conditions with cells (human and porcine) harvested from the TMJ
      disc or the articular eminence. The specimens were examined by scanning electron
      microscopy and transmission electron microscopy. The type of collagen synthesized
      was analyzed by SDS-PAGE. The cells were strongly adherent to all of the
      materials. Independent of their origin the cells became confluent on all
      scaffolds within four weeks. They filled recesses loosely and covered the
      constructs by an envelope of dense stratified cell layers. Moreover, the cells
      expressed collagen type II, which is specific for chondrocytes. Thus, it could be
      demonstrated, that ePTFE, polyamide, polyglycolic acid and natural bone mineral
      have an excellent compatibility in a three-dimensional cell culture system. ePTFE
      and polyamide scaffolds may be well suited for the development of tissue
      engineered stress-resistant articular disc transplants.

PMID- 11516091
TI  - Allogeneic and autologous transplantation for chronic lymphocytic leukemia.
AB  - Autologous and allogeneic transplantation are increasingly used in the management
      of patients with chronic lymphocytic leukemia. Many questions regarding patient
      selection, efficacy and outcome are unresolved, hence a review of the literature
      through Medline search. Autologous transplantation for CLL has been used mainly
      in selected patients under the age of 60. Conditioning typically involves total
      body irradiation (TBI). Bone marrow and more recently peripheral blood stem cells
      are used. Treatment-related mortality in most series is less than 10%. Molecular
      remissions after autologous transplantation are common, and clinical remissions
      can be prolonged in some patients. Randomized studies are needed to establish
      whether autologous transplantation confers a survival benefit over standard
      chemotherapy approaches. Allogeneic transplantation has a considerable treatment
      related mortality, but durable remissions sometimes occur in patients with
      advanced disease. The use of non-myeloablative 'mini-transplants' has been
      investigated as a method to reduce treatment-related mortality, but prolonged
      follow-up will be required to establish the cure rate obtained with this
      procedure. Autologous and allogeneic transplantation are promising treatment
      modalities. Further refinements of transplant techniques and properly designed
      prospective studies are necessary to establish the role of stem cell
      transplantation in the overall management of CLL.

PMID- 11516092
TI  - Impact of treatment on the outcome of acute myeloid leukemia with inversion 16: a
      single institution's experience.
AB  - To identify treatment factors that may affect the survival of children with
      inv(16)(p13.1q22), we compared the outcomes of 19 patients with this genetic
      feature treated at our institution during two treatment eras. Nine patients were
      treated during era 1 (1980 to 1987), and 10 were treated during era 2 (1988 to
      1996). All entered complete remission (CR) with induction therapy. Eight of the
      nine children treated in era 1 died, seven of relapsed leukemia. In contrast,
      three of 10 patients treated during era 2 have died, all of non-disease-related
      causes. Event-free survival (EFS) estimates were significantly higher for
      patients treated during era 2 than for those treated during era 1 (P = 0.03); the
      6-year estimates were 70 +/- 15% (s.e.) and 11 +/- 7%, respectively. Era 2
      treatment protocols differed from those of era 1 in their use of higher doses of
      cytarabine and etoposide during induction and consolidation chemotherapy and in
      their use of 2-chlorodeoxyadenosine (2-CDA). These results suggest that dose
      intensification of cytarabine benefits children with AML and inv(16), as is the
      case in adults. They also suggest that dose intensification of etoposide and
      addition of 2-CDA may also offer an advantage. This study underscores the
      dependence of the prognostic impact of cytogenetic features on the efficacy of
      treatment.

PMID- 11516094
TI  - Induction of graft-versus-leukemia to prevent relapse after partially lymphocyte
      depleted allogeneic bone marrow transplantation by pre-emptive donor leukocyte
      infusions.
AB  - In this prospective study we analyzed pre-emptive donor leukocyte infusions (DLI)
      in 82 consecutive patients transplanted with partially T cell-depleted grafts for
      acute myeloid leukemia, acute lymphoid leukemia, chronic myeloid leukemia,
      refractory anemia with excess of blasts, refractory anemia with excess of blasts
      in transformation and multiple myeloma. Donors were HLA-identical siblings.
      Patients without significant acute (>grade 1) and/or chronic GVHD were scheduled
      to be treated with DLI (35 patients) and 31 actually received DLI. Patients who
      developed acute GVHD >grade 1 and/or chronic GVHD were not scheduled to receive
      DLI and served as a comparison group (47 patients). The median interval between
      BMT and DLI was 22 weeks. The first six patients received 0.7 x 10(8) CD3+
      cells/kg body weight (b.w.). Five out of these six patients developed acute GVHD
      (grade 1: n = 2, grade 3: n = 2 and grade 4: n= 1) which was more frequent and
      more severe than we had anticipated. In the next 25 patients the number of T
      lymphocytes was diminished to 0.1 x 10(8) CD3+ cells/kg b.w. which resulted in
      less frequent and less severe GVHD. Eight patients in this group developed acute
      GVHD (grade 1: n = 4, grade 2: n = 4) and three patients had limited chronic
      GVHD. Patients in the DLI group needed more time to establish complete donor
      chimerism confirmed by a higher number of mixed chimeras at 6 months after BMT.
      The projected 3-year probability of disease-free survival was 77% for the 35
      patients intended to treat with DLI and 45% for the patients of the comparison
      group (P = 0.024). Relapse rate at 36 months after transplantation was 18% in the
      patients who were intended to treat with DLI and 44% in the comparison group (P =
      0.026). We conclude that pre-emptive DLI is feasible and generates favorable
      relapse rates in patients who are at high risk for relapse. Furthermore, the
      incidence and severity of GVHD disease after DLI is dependent on the number of
      CD3+ cells infused.

PMID- 11516093
TI  - Effects of glycosylated recombinant human granulocyte colony-stimulating factor
      after high-dose cytarabine-based induction chemotherapy for adult acute myeloid
      leukaemia.
AB  - The Australian Leukaemia Study Group (ALSG) investigated whether G-CSF would
      accelerate haemopoietic recovery after induction treatment for acute myeloid
      leukaemia (AML) intensified with high-dose cytarabine, and therefore improve
      response rates and survival. Patients were randomised to receive lenograstim
      (glycosylated recombinant human G-CSF) 5 microg per kg body weight subcutaneously
      daily from day 8 after starting chemotherapy, or no cytokine, following
      chemotherapy with cytarabine 3 g/m2 every 12 h on days 1, 3, 5, and 7, together
      with idarubicin 9 or 12 mg/m2 on days 1, 2, and 3, plus etoposide 75 mg/m2 on
      days 1 to 7 inclusive. Patients had untreated AML, and were aged 16 to 60 years.
      Overall, 54 evaluable patients were randomised to receive lenograstim and 58 to
      no cytokine. Patients in the lenograstim arm had a significantly shorter duration
      of neutropenia <0.5 x 10(9)/l compared to patients in the no cytokine arm (median
      18 vs 22 days; P = 0.0005), and also shorter duration of total leucopenia <1.0 x
      10(9)/l (17 vs 19 days; P = 0.0002), as well as a reduction in duration of
      treatment with therapeutic intravenous antibiotics (20 vs 24 days; P= 0.015) and
      a trend to reduced number of days with fever >38.0 degrees C (9 vs 12 days; P =
      0.18). There were no differences between the two groups in platelet recovery, red
      cell or platelet transfusions, or non-haematological toxicities. For patients
      achieving CR after their first induction course, a reduction in the time to the
      start of the next course of therapy was observed in the lenograstim arm, from a
      median of 40.5 days to a median of 36 days (P = 0.082). The overall complete
      response rates to chemotherapy were similar, 81% in the lenograstim arm vs 75%
      for the no cytokine arm (P = 0.5), and there was no significant difference in the
      survival durations. We conclude that the granulopoietic stimulating effect of G
      CSF is observed after induction therapy for AML intensified by high-dose
      cytarabine, resulting in an improvement in a number of clinically important
      parameters with no major adverse effects.

PMID- 11516095
TI  - Stromal support augments extended long-term ex vivo expansion of hemopoietic
      progenitor cells.
AB  - Current technology to numerically expand hemopoietic stem/progenitor cells (HSPC)
      ex vivo within 1 to 2 weeks is insufficient to warrant significant gain in
      reconstitution time following their transplantation. In order to more stringently
      test the parameters affecting HSPC expansion, we followed ex vivo cultures of
      CD34+-selected umbilical cord blood (UCB) HSPC for up to 10 weeks and
      investigated the effects of stromal support and cytokine addition. The cytokine
      combinations included FL + TPO, FL + TPO plus SCF and/or IL6, or SCF + IL6. To
      identify the HSPC in uncultured and cultured material, we determined the number
      of colony-forming cells (CFC), cobblestone area forming cells (CAFC), the
      NOD/SCID repopulating ability (SRA), and CD34+ subsets by phenotyping. The
      highest fold-increase obtained for CD34+ and CD34+ CD38- cell numbers was,
      respectively, 1197 and 30,937 for stroma-free and 4066 and 117,235 for stroma
      supported cultures. In general, CFC generation increased weekly in FL + TPO
      containing groups up to week 5 with a 28- to 195-fold expansion whereafter the
      weekly CFC output stabilized. Stroma support enhanced the expansion of CAFC week
      6 maximally 11-fold to 89-fold with FL + TPO + IL6. Cultures stimulated with at
      least FL + TPO gave an estimated 10- to 14-fold expansion of the ability of CD34+
      UCB cells to multilineage engraft the BM of sublethally irradiated NOD/SCID mice
      at 2 weeks of stroma-free and stroma-supported cultures, while at week 5 and
      later the estimated SRA decreased to low or undetectable levels in all groups.
      Our results show that stroma and FL + TPO but also inclusion of bovine serum
      albumin, greatly increase the long-term generation of HSPC as measured by in
      vitro assays and is indispensable for long-term expansion of CD34+ CD38- CXCR4+
      cells. However, the different surrogate methods to quantify the HSPC (CD34+ CD38
      , CFC, CAFC week 6 and SRA) show increasing incongruency with increasing culture
      time, while especially the phenotypic analysis and the CFC generation greatly
      overestimate the CAFC and SRA expansion in 10-week cultures.

PMID- 11516097
TI  - Prognostic evaluation of the microvascular network in myelodysplastic syndromes.
AB  - Considering the recently stated suggestion of neovascularization being implicated
      in myelodysplastic syndromes (MDS) pathogenesis, we evaluated multiple
      morphometric microvascular characteristics in MDS, in relation to
      clinicopathologic factors and prognosis. Trephines from 50 newly diagnosed MDS
      patients were immunostained for factor VIII and compared to those from 20
      controls, 10 chronic myelomonocytic leukemia (CMML) and 12 acute myeloid leukemia
      (AML) patients. Quantitation of microvessel density (MVD), area, total vascular
      area (TVA), major and minor axis length, perimeter, compactness, shape factor,
      Feret diameter, and the number of branching vessels was performed by image
      analysis. Overall, the MDS group had significantly higher MVD, TVA, minor axis
      and shape factor values and significantly lower compactness than the control
      group. AML was characterized by increased vascularity compared to MDS and CMML,
      as well as by the presence of flattened microvessels (lower values of shape
      factor). Hypercellular MDS showed higher MVD. RA/RARS displayed larger caliber
      vessels than RAEB, which explains the favorable prognostic effect of increased
      size-related parameters on progression and/or survival. Moreover, decreased
      compactness and MVD were independent predictors of longer progression-free
      survival. It is concluded that angiogenesis is involved in the conversion of
      normal marrow to MDS and ultimately to AML and that disease progression within
      MDS is accompanied by qualitative alterations of the microvascular network.
      Furthermore, size-related parameters affect survival, while shape-related
      parameters and MVD are more influential with regard to progression-free survival.

PMID- 11516096
TI  - Molecular cytogenetic characterization and clinical relevance of additional,
      complex and/or variant chromosome abnormalities in acute promyelocytic leukemia.
AB  - Acute promyelocytic leukemia (APL) is characterized by typical morphological
      manifestation, t(15;17) translocation and active response to all-trans retinoic
      acid (ATRA) in the great majority of patients. However, a subset of APL cases may
      present atypical phenotypic, cytogenetic or molecular features at different
      stages of the disease. The biological and clinical significance of these features
      sometimes remains obscure. In this study, 284 APL patients were cytogenetically
      analyzed and precise diagnosis was performed according to the molecular
      cytogenetic results. Twenty-six APL patients were identified as having
      additional, complex and/or variant chromosomal abnormalities at diagnosis or at
      relapse, 16 of them being further analyzed using fluorescence in situ
      hybridization (FISH) or chromosome painting (CP). Interestingly, some of these
      chromosomal aberrations were found to be associated with atypical morphology
      and/or drug response, indicating a genotype-phenotype correlation. Analysis of
      the complex karyotype may also allow a better understanding of the levels of
      cellular origin of the leukemogenesis. Examination of the remission induction and
      survival data showed that the presence of the additional/complex chromosome
      abnormalities was related to the prognosis in both primarily diagnosed and
      relapsed patients in this series.

PMID- 11516098
TI  - Induction of chemoresistance in HL-60 cells concomitantly causes a resistance to
      apoptosis and the synthesis of P-glycoprotein.
AB  - The appearance of multidrug-resistant (MDR) proteins or the acquisition of a
      defective apoptotic programme are major drawbacks in the treatment of cancers
      since both induce a resistance to classical chemotherapy. However, a link between
      the two mechanisms has not, as yet, been clearly established. In this study, HL
      60 cells cultured in the continual presence of a sub-lethal dose of doxorubicin
      (dox; HL-60/Dox) were used as a model to study acquired chemoresistance. During
      the induction of chemoresistance, the appearance of a functional P-glycoprotein
      (P-gp), in addition to the expression of anti-apoptotic Bcl-2, Bcl-XL and pro
      apoptotic Bax proteins was assessed. Parental cells which are sensitive to dox,
      have no P-gp activity and express Bcl-2 and Bax. After 4 weeks of treatment, a
      functional P-gp was detected in HL-60/Dox cells. In addition, the synthesis of
      Bcl-2 appeared to be replaced by Bcl-XL while that of Bax remained unchanged.
      These cells were also resistant to apoptosis induced by both P-gp and non-P-gp
      substrates. This inability to induce apoptosis could have resulted from the
      induction of the expression of the inhibitor of apoptosis protein (XIAP). Our
      data show that acquired chemoresistance could involve a parallel induction of P
      gp and an impairment of the apoptotic pathway.

PMID- 11516099
TI  - Proteasome inhibitor-induced apoptosis of B-chronic lymphocytic leukaemia cells
      involves cytochrome c release and caspase activation, accompanied by formation of
      an approximately 700 kDa Apaf-1 containing apoptosome complex.
AB  - Proteasome inhibitors, including lactacystin and MG132 (carbobenzoxyl-leucinyl
      leucinyl-leucinal), potently induce apoptosis in leukaemic B cells from patients
      with B cell chronic lymphocytic leukaemia (B-CLL). This pro-apoptotic effect
      occurs in cells from patients at all stages of the disease, including those
      resistant to conventional chemotherapy, suggesting that proteasome inhibitors may
      be useful for treatment of B-CLL. Following initial inhibition of proteasomal
      activity, these agents induce mitochondrial cytochrome c release and caspase
      dependent apoptosis, involving cleavage/activation of caspases -2, -3, -7, -8 and
      -9. Pre-treatment with the cell permeable caspase inhibitor, benzyloxycarbonyl
      Val-Ala-Asp (OMe)fluoromethyl ketone (Z-VAD.fmk), did not prevent the release of
      cytochrome c or partial processing of caspase-9 but prevented activation of
      effector caspases and the induction of apoptosis. These results suggest that the
      release of cytochrome c is caspase independent and that caspase-9 is the
      initiator caspase in proteasome inhibitor-induced apoptosis of B-CLL cells.
      Activation of B-CLL lysates with dATP results in the formation of an
      approximately 700 kDa caspase-activating apoptosome complex containing Apaf-1. We
      describe for the first time the formation of a similar approximately 700 kDa
      caspase-activating apoptosome complex in B-CLL cells induced to undergo apoptosis
      by proteasome inhibitors.

PMID- 11516100
TI  - Blocking protein geranylgeranylation is essential for lovastatin-induced
      apoptosis of human acute myeloid leukemia cells.
AB  - Lovastatin is an inhibitor of the enzyme 3-hydroxy-3-methylglutaryl coenzyme A
      (HMG-CoA) reductase, the major regulatory enzyme of the mevalonate pathway. We
      have previously reported that lovastatin induces a significant apoptotic response
      in human acute myeloid leukemia (AML) cells. To identify the critical biochemical
      mechanism(s) essential for lovastatin-induced apoptosis, add-back experiments
      were conducted to determine which downstream product(s) of the mevalonate pathway
      could suppress this apoptotic response. Apoptosis induced by lovastatin was
      abrogated by mevalonate (MVA) and geranylgeranyl pyrophosphate (GGPP), and was
      partially inhibited by farnesyl pyrophosphate (FPP). Other products of the
      mevalonate pathway including cholesterol, squalene, lanosterol, desmosterol,
      dolichol, dolichol phosphate, ubiquinone, and isopentenyladenine did not affect
      lovastatin-induced apoptosis in AML cells. Our results suggest that inhibiting
      geranylgeranylation of target proteins is the predominant mechanism of lovastatin
      induced apoptosis in AML cells. In support of this hypothesis, the geranylgeranyl
      transferase inhibitor (GGTI-298) mimicked the effect of lovastatin, whereas the
      farnesyl transferase inhibitor (FTI-277) was much less effective at triggering
      apoptosis in AML cells. Inhibition of geranylgeranylation was monitored and
      associated with the apoptotic response induced by lovastatin and GGTI-298 in the
      AML cells. We conclude that blockage of the mevalonate pathway, particularly
      inhibition of protein geranylgeranylation holds a critical role in the mechanism
      of lovastatin-induced apoptosis in AML cells.

PMID- 11516101
TI  - Minimal residual disease (MRD) in remission t(8;21) AML and in vivo
      differentiation detected by FISH and CD34+ cell sorting.
AB  - Many patients with t(8;21) AML have residual positive cells during remission. We
      previously developed D-FISH probes that detect both derivative chromosomes and
      the normal alleles. In negative controls, only 2/44,000 (0.0045%) positive
      signals were observed. To investigate MRD, we examined specimens from 29 patients
      who had initially obtained CR. In remission patients, 61% had 1-4/2000 positive
      cells (0.05-0.19%). Higher frequencies were found in two patients in early
      relapse and in one patient in early remission. However, a negative test did not
      exclude relapse. Since false positives were negligible and because most t(8;21)
      AMLs express CD34, we asked whether cell sorting combined with FISH would
      increase the sensitivity. In one patient, we observed that 80% of CD34+ cells
      were t(8;21)+ at 2 months from initial clinical and cytogenetic remission.
      However, by 5 months the pre- and post-sorted populations contained 0.15% and
      0.06% t(8;21) cells, respectively. Whereas essentially all t(8;21) cells in the
      initial specimen expressed CD34, only 0.6% were subsequently CD34+. These results
      are consistent with in vitro assays showing that residual t(8;21) cells undergo
      differentiation. Thus, FISH can identify MRD in a majority of t(8;21) patients
      and, combined with CD34+ selection, may provide an indirect assessment of the
      differentiation state of residual t(8;21) cells.

PMID- 11516102
TI  - Precursor-B-ALL with D(H)-J(H) gene rearrangements have an immature
      immunogenotype with a high frequency of oligoclonality and hyperdiploidy of
      chromosome 14.
AB  - The IGH gene configuration was investigated in 97 childhood precursor-B-ALL
      patients at initial diagnosis. Rearrangements were found by Southern blotting in
      all but three patients (97%) and in 30 cases (31%) we observed oligoclonal IGH
      gene rearrangements. Heteroduplex PCR analysis revealed at least one clonal PCR
      product in all Southern blot-positive cases. In 89 patients (92%) complete V(D)J
      rearrangements were found, while incomplete D(H)-J(H) rearrangements occurred in
      only 21 patients (22%). In 5% of cases the D(H)-J(H) rearrangements were the sole
      IGH gene rearrangements. Sequence analysis of the 31 identified incomplete
      rearrangements revealed preferential usage of segments from the D(H)2, D(H)3 and
      D(H)7 families (78%). While D(H)2 and D(H)3 gene rearrangements occur frequently
      in normal B cells and B cell precursors, the relatively frequent usage of D(H)7
      27 (19%) in precursor-B-ALL patients is suggestive of leukemic transformation
      during prenatal lymphopoiesis. Among J(H) gene segments in the incomplete D(H)
      J(H) rearrangements, the J(H)6 segment was significantly overrepresented (61%).
      This observation together with the predominant usage of the most upstream D(H)
      genes indicates that many of the identified clonal D(H)-J(H) gene rearrangements
      in precursor-B-ALL probably represent secondary recombinations, having deleted
      pre-existing D(H)-J(H) joinings. The patients with incomplete D(H)-J(H) gene
      rearrangements were frequently characterized by hyperdiploid karyotype with
      additional copies of chromosome 14 and/or by IGH oligoclonality. The presence of
      incomplete D(H)-J(H) joinings was also significantly associated with a less
      mature immunogenotype: overrepresentation of V(H)6-1 gene segment usage, absence
      of biallelic TCRD deletions, and low frequency of TCRG gene rearrangements. This
      immature immunogenotype of precursor-B-ALL with incomplete IGH gene
      rearrangements was not associated with more aggressive disease.

PMID- 11516103
TI  - Role of the tyrosine phosphatase SHP-1 in K562 cell differentiation.
AB  - The erythro-megakaryoblastic leukemia cell line K562 undergoes erythroid or
      myeloid differentiation in response to treatment with various inducing agents. We
      observed that expression of the SH2-containing protein tyrosine phosphatase SHP-1
      was induced upon exposure of K562 cells to differentiating agents. Under the same
      conditions, expression of SHP-2, a close relative of SHP-1, and the more
      distantly related PTP-1 B remained unchanged. Induction of SHP-1 expression
      correlates with dephosphorylation of a specific and limited set of tyrosyl
      phosphoproteins, suggesting that dephosphorylation of these proteins may be
      important for the differentiation process. Importantly, expression of exogenous
      SHP-1 inhibits K562 proliferation and alters the adhesion properties of these
      cells, indicating a more differentiated phenotype. Moreover, SHP-1 is found in a
      complex with both p210 Bcr-Abl and p190 Bcr-Abl, suggesting that it may regulate
      Bcr-Abl or Bcr-Abl-associated phosphotyrosyl proteins. Our results indicate that
      induction of SHP-1 expression is important for K562 differentiation in response
      to various inducers and raise the possibility that functional inactivation of SHP
      1 may play a role in progression to blast crisis in chronic myelogenous leukemia.

PMID- 11516104
TI  - Regulation of the acute myeloid leukemia cell line OCI/AML-2 by endothelial
      nitric oxide synthase under the control of a vascular endothelial growth factor
      signaling system.
AB  - It is generally accepted that the vascular endothelial growth factor (VEGF)
      signal system has no role in the maintenance of normal blood cell formation,
      although it obviously regulates the development of primitive hematopoiesis during
      an early stage of embryogenesis. The VEGF signaling pathway, however, might have
      some role in malignant hematopoiesis, since malignant hematopoietic cells,
      including acute myeloid leukemia (AML) cells, have been shown to express VEGF and
      its receptors. In endothelial cells, the VEGF/Flk-1/KDR signal system is a very
      important generator of nitric oxide (NO) through the activation of its downstream
      effectors phosphatidylinositol-3-OH-kinase (PI3-K), Akt kinase and endothelial NO
      synthase (eNOS). It is known that NO regulates hematopoiesis and modulates AML
      cell growth. The role of the VEGF signaling pathway in the control of AML cell
      growth through eNOS, however, has not been studied. By using the OCI/AML-2 cell
      line, which expresses VEGF receptor-2, ie Flk-1/KDR, eNOS and VEGF, as analyzed
      by flow cytometry, and produces VEGF into growth medium, as analyzed by ELISA, we
      showed that the Akt kinase and NOS activities in these cells were decreased by
      the inhibitors of VEGF, Flk-1/KDR and PI3-K, and NOS activity also by the direct
      inhibitor of NOS. The decreased NOS activity led to inhibition of clonogenic cell
      growth and, to some extent, induction of apoptosis. We also found that blast
      cells of bone marrow samples randomly taken from 14 AML patients uniformly
      expressed Flk-1/KDR and to varying degrees eNOS and VEGF, as analyzed by
      immunohistochemistry. We conclude that autocrine VEGF through Flk-1/KDR, by
      activating eNOS to produce NO through PI3-K/Akt kinase, maintains clonogenic cell
      growth in the OCI/AML-2 cell line. Since the patient samples did not express VEGF
      in all cases, it is possible that in vivo the regulatory connection between these
      two signal systems is also mediated via endocrine VEGF in addition to autocrine
      or paracrine VEGF.

PMID- 11516105
TI  - Characterization of additional genetic events in childhood acute lymphoblastic
      leukemia with TEL/AML1 gene fusion: a molecular cytogenetics study.
AB  - TEL/AML1 gene fusion that results from a cryptic t(12;21) is the most common
      genetic aberration in childhood B-lineage acute lymphoblastic leukemia (ALL).
      While the translocation may initiate the leukemic process, critical secondary
      genetic events are currently believed to be pivotal for leukemogenesis. We
      investigated 12 cases of childhood ALL with TEL/AML1 gene fusion by fluorescence
      in situ hybridization (FISH) and comparative genomic hybridization (CGH) and
      documented additional or secondary genetic changes in seven patients (58%). Three
      patients showed extra copies of chromosome 21 including a case in which the
      trisomy 21 (+21) clone was distinct from the one harboring TEL/AML1 gene fusion.
      Interestingly, one patient without +21 showed amplification of the AML1 gene on
      chromosome 21q, supporting the contention that AML1 amplification may be an
      important additional genetic event. Gene expression study by semi-quantitative
      reverse-transcription polymerase chain reaction (RT-PCR) in two of these four
      patients showed an increase in AML1 transcripts that paralleled the increase in
      gene copy number. Deletion of the normal TEL allele was detected in two patients,
      with one of them showing loss of chromosome 12 together with duplication of the
      der(12)t(12;21). Finally, one patient showed duplication of the fusion signal.
      Our findings confirm that additional or secondary genetic changes including AML1
      amplification are commonly encountered in childhood ALL with TEL/AML1 gene
      fusion, which are envisaged to play significant roles in disease progression.

PMID- 11516106
TI  - Investigation on the role of the ATM gene in chronic myeloid leukaemia.
AB  - Chronic myeloid leukaemia (CML) is characterised by an indolent, chronic phase
      (CP) preceding an acute transformation to blast crisis (BC). While the BCR-ABL
      fusion oncogene is strongly implicated in the CP, the molecular changes
      underlying BC are largely unknown. The ataxia telangiectasia gene, ATM, is a
      candidate gene for this transformation because the complex karyotypes associated
      with BC of CML suggest that DNA double-strand break repair is defective and
      because the ABL pathway involves the interaction between the Abl and the Atm
      proteins. We performed a mutational analysis for ATM in CML using genomic DNA
      from 14 CML cell lines and 59 CML patients in BC. No clearly deleterious
      nucleotide changes were observed. A new polymorphism C4138T was discovered which
      results in a non-conservative amino acid substitution (H1380Y). This variant lies
      in the Atm recognition motif for the Abl protein. While ATM is unlikely to
      contribute substantially to CML, further investigation of the H1380Y substitution
      should clarify whether it has any functional effect.

PMID- 11516107
TI  - T cell activation following infection of primary follicle center lymphoma B cells
      with adenovirus encoding CD154.
AB  - Purified, high-titer adenovirus encoding murine CD154 (Ad-CD154) or human CD154
      (Ad-hCD154) was used to infect lymph node cells isolated from patients with
      follicle center lymphoma. Infection of lymphoma B cells with Ad-CD154 at a
      multiplicity of infection (MOI) ratio of 100 or higher resulted in high-level
      transgene expression. Additionally, upon infection of lymphoma B cells, only Ad
      CD154 resulted in surface expression of CD154, despite similar, high-level
      expression of either human or mouse CD154 by HeLa cells infected with Ad-hCD154
      or Ad-CD154, respectively. Moreover, infection of lymphoma B cells with Ad-CD154,
      but not Ad-hCD154 or adenovirus encoding Eschericheria coli beta-galactosidase
      (Ad-LacZ), induced the neoplastic B cells to express higher levels of immune co
      stimulatory molecules that are required for proficient presentation of antigen to
      T cells. Consistent with this, we found that Ad-CD154 infected lymphoma B cells
      could stimulate T cells to proliferate or produce interferon-gamma in allogeneic
      or autologous mixed lymphocyte interactions. We conclude that lymphoma B cells
      can be infected with Ad-CD154 and that this significantly enhances their
      recognition by allogeneic or autologous T cells. As such, Ad-CD154-transduced
      lymphoma B cells may have potential for the active immune therapy of patients
      with follicle center lymphoma.

PMID- 11516108
TI  - Atypical lymphocytic leukemia and mantle cell lymphoma immunologically very
      close: flow cytometric distinction by the use of CD20 and CD54 expression.
AB  - Integration of morphological and immunophenotypic data is critical in achieving
      diagnosis accuracy and minimising interobserver interpretative discrepancies. The
      aim of this work was to compare the immunophenotype and the morphology of chronic
      lymphocytic leukaemia and mantle cell lymphoma, to help in the differential
      diagnosis of CD5 positive monoclonal B cells. Frozen/thawed samples from 91
      patients were analysed retrospectively. Fresh samples from 17 mixed/atypical CLL
      and 13 MCL were tested to corroborate the results. Markers were analysed as
      percentage (%) of positive B lymphocyte subpopulation, and in terms of median
      fluorescence intensity (MFI). Matutes's CLL score clearly allowed distinguishing
      between classical CLL on the one hand, and atypical CLL and MCL on the other
      hand. The percentage of CD54-positive cells and the median fluorescence intensity
      of CD20 and CD54 were the only parameters which were significantly higher in MCL
      than in atypical CLL (P < 0.05), allowing an immunological distinction between
      these two entities. Nevertheless, due to a quenching problem when using CD20 and
      CD54 together, and because CD18 showed a statistically different expression
      between classical and atypical CLL, the combination of CD18/CD54 has been
      preferred and showed a different pattern in the three entities. Immunophenotyping
      could be helpful in the differential diagnosis of CD5-positive B cell chronic
      lymphoproliferative disorders with atypical features that do not fit exactly into
      any of the morphologic proposed groups.

PMID- 11516109
TI  - Evaluating treatment strategies in advanced Waldenstrom macroglobulinemia: use of
      quality-adjusted survival analysis.
AB  - A randomized phase II multicenter clinical trial comparing the efficacy of
      fludarabine (FAMP) to that of the association of cyclophosphamide, doxorubicin
      and prednisone (CAP) in 92 patients with Waldenstrom's macroglobulinemia in first
      relapse or with primarily resistant disease, was conducted on the behalf of the
      'Groupe Cooperatif Macroglobulinemie'. The main analysis of this study failed to
      demonstrate a clear cut benefit of FAMP in terms of overall survival (OS),
      although a significant benefit in terms of time to disease progression and event
      free survival (EFS) was noted. In this rare disorder, where few randomized trials
      have been conducted, we took advantage of this trial to assess treatment
      differences while integrating quality of life considerations. We thus performed a
      quality-adjusted survival analysis, using the quality-adjusted time without
      symptoms or toxicity (Q-TWiST) approach. Four health states differing in terms of
      quality of life (QoL) were defined, namely treatment-related toxicity, treatment
      free of toxicity, no treatment or symptoms, and relapse. The average time spent
      in these health states (TOX, CT, TWiST and REL, respectively) were then weighted
      by utility coefficients reflecting relative QoL value according to that of TWiST
      and summed up giving the so-called Q-TWiST. No difference was found between
      randomized groups in terms of mean CT. Mean TOX in the two groups were similarly
      close except when considering alopecia as a relevant toxic event. By contrast,
      mean TWiST was 5.9 months longer in the FAMP group than in the CAP group (P =
      0.006). Unsurprisingly, given the absence of difference in OS but the difference
      in EFS in favor of the FAMP group, mean REL was increased by 6.8 months in the
      CAP group (P = 0.047). As a result, benefit of FAMP in terms of average Q-TWiST
      only relied on the value of the utility coefficient attributed to REL (U(REL)),
      with a significant benefit when UREL ranged from 0 to 0.28, ie in patients
      undergoing poor QoL after relapse, which is likely.

PMID- 11516110
TI  - Establishment of the B cell precursor acute lymphoblastic leukemia cell line MUTZ
      5 carrying a (12:13) translocation.
AB  - Continuous leukemia-lymphoma cell lines are important research tools, in
      particular as starting material for the cloning of recurrent translocations. In
      1998, we established the continuous leukemia cell line MUTZ-5 and its two
      simultaneous sister cell lines MUTZ-6 and MUTZ-7. The primary specimen was
      obtained from the peripheral blood of a 26-year-old man with B cell precursor
      acute lymphoblastic leukemia at relapse carrying a t(12;13). The immunoprofile of
      MUTZ-5 corresponds to that of a precursor B cell. The immunoglobulin heavy chain
      gene was found to be rearranged. Despite receptor expression, none of the
      cytokines examined enhanced proliferation; several cytokines had significant
      inhibitory effects. Giemsa-banding cytogenetics showed the following karyotype
      which was identical in all three sister cell lines: 45<2n>X, -Y, t(12;13)(p12;q13
      14). The karyotype and DNA fingerprinting confirmed the malignant nature and the
      authenticity of the cell line, excluding cross-contamination with other cells.
      MUTZ-5 represents a new unique leukemia B cell line; its scientific significance
      lies in the t(12;13).

PMID- 11516111
TI  - Detection of translocations affecting the BCL6 locus in B cell non-Hodgkin's
      lymphoma by interphase fluorescence in situ hybridization.
AB  - Structural alterations in 3q27 affecting the BCL6 locus are among the most
      frequent changes in B-NHL. The aim of the present study was to establish an
      interphase-FISH assay for the detection of all diverse BCL6 translocations in B
      NHL. Two different approaches were tested, one using a PAC-clone spanning the
      major breakpoint region (MBR) of BCL6 (span-assay), and another using two BAC
      clones flanking the MBR (flank-assay). Interphase FISH with the span-assay
      detected the various BCL6 translocations in seven B-NHL cell lines. The dual
      color flank-assay was evaluated in two laboratories independently: in normal
      controls, the cutoff level for false-positive signals was 2.6%, whereas the
      cutoff level for false-negatives in the seven cell lines was 7.5%. To test the
      feasibility of the FISH strategies, 30 samples from patients with B-NHL with
      cytogenetic abnormalities of 3q27 were evaluated with both assays. In 21 cases,
      the span-assay indicated a BCL6 rearrangement. In 18 of the 21 cases, the dual
      color flank-assay confirmed the translocation including 12 different partner
      chromosomal loci. The three false-positive cases detected with the span-assay
      showed trisomy of chromosome 3 by cytogenetic analyses, and they were correctly
      classified as non-rearranged with the flank-assay. In summary, our FISH strategy
      using two differently labeled flanking BCL6 BAC probes provides a robust,
      sensitive, and reproducible method for the detection of common and uncommon
      abnormalities of BCL6 gene in interphase nuclei. The routine application of this
      assay to patients with B-NHL will allow the assessment of the diagnostic and
      prognostic significance of BCL6 rearrangements.

PMID- 11516112
TI  - Real-time quantitative PCR for detection of minimal residual disease before
      allogeneic stem cell transplantation predicts outcome in children with acute
      lymphoblastic leukemia.

PMID- 11516113
TI  - Risk-sensitive choice in humans as a function of an earnings budget.
AB  - Risky choice in 3 adult humans was investigated across procedural manipulations
      designed to model energy-budget manipulations conducted with nonhumans. Subjects
      were presented with repeated choices between a fixed and a variable number of
      points. An energy budget was simulated by use of an earnings budget, defined as
      the number of points needed within a block of trials for points to be exchanged
      for money. During positive earnings-budget conditions, exclusive preference for
      the fixed option met the earnings requirement. During negative earnings-budget
      conditions, exclusive preference for the certain option did not meet the earnings
      requirement, but choice for the variable option met the requirement
      probabilistically. Choice was generally risk averse (the fixed option was
      preferred) when the earnings budget was positive and risk prone (the variable
      option was preferred) when the earnings budget was negative. Furthermore, choice
      was most risk prone during negative earnings-budget conditions in which the
      earnings requirement was most stringent. Local choice patterns were also
      frequently consistent with the predictions of a dynamic optimization model,
      indicating that choice was simultaneously sensitive to short-term choice
      contingencies, current point earnings, and the earnings requirement. Overall,
      these results show that the patterns of risky choice generated by energy-budget
      variables can also be produced by choice contingencies that do not involve
      immediate survival, and that risky choice in humans may be similar to that shown
      in nonhumans when choice is studied under analogous experimental conditions.

PMID- 11516114
TI  - Group choice: the ideal free distribution of human social behavior.
AB  - Group choice refers to the distribution of group members between two choice
      alternatives over time. The ideal free distribution (IFD), an optimal foraging
      model from behavioral ecology, predicts that the ratio of foragers at two
      resource sites should equal the ratio of obtained resources, a prediction that is
      formally analogous to the matching law of individual choice, except that group
      choice is a social phenomenon. Two experiments investigated the usefulness of IFD
      analyses of human group choice and individual-based explanations that might
      account for the group-level events. Instead of nonhuman animals foraging at two
      sites for resources, a group of humans chose blue and red cards to receive points
      that could earn cash prizes. The groups chose blue and red cards in ratios in
      positive relation to the ratios of points associated with the cards. When group
      choice ratios and point ratios were plotted on logarithmic coordinates and fitted
      with regression lines, the slopes (i.e., sensitivity measures) approached 1.0 but
      tended to fall short of it (i.e., undermatching), with little bias and little
      unaccounted for variance. These experiments demonstrate that an IFD analysis of
      group choice is possible and useful, and suggest that group choice may be
      explained by the individual members' tendency to optimize reinforcement.

PMID- 11516115
TI  - Variable-ratio versus variable-interval schedules: response rate, resistance to
      change, and preference.
AB  - Two experiments asked whether resistance to change depended on variable-ratio as
      opposed to variable-interval contingencies of reinforcement and the different
      response rates they establish. In Experiment 1, pigeons were trained on multiple
      random-ratio random-interval schedules with equated reinforcer rates. Baseline
      response rates were disrupted by intercomponent food, extinction, and prefeeding.
      Resistance to change relative to baseline was greater in the interval component,
      and the difference was correlated with the extent to which baseline response
      rates were higher in the ratio component. In Experiment 2, pigeons were trained
      on multiple variable-ratio variable-interval schedules in one half of each
      session and on concurrent chains in the other half in which the terminal links
      corresponded to the multiple-schedule components. The schedules were varied over
      six conditions, including two with equated reinforcer rates. In concurrent
      chains, preference strongly overmatched the ratio of obtained reinforcer rates.
      In multiple schedules, relative resistance to response-independent food during
      intercomponent intervals, extinction, and intercomponent food plus extinction
      depended on the ratio of obtained reinforcer rates but was less sensitive than
      was preference. When reinforcer rates were similar, both preference and relative
      resistance were greater for the variable-interval schedule, and the differences
      were correlated with the extent to which baseline response rates were higher on
      the variable-ratio schedule, confirming the results of Experiment 1. These
      results demonstrate that resistance to change and preference depend in part on
      response rate as well as obtained reinforcer rate, and challenge the independence
      of resistance to change and preference with respect to response rate proposed by
      behavioral momentum theory.

PMID- 11516116
TI  - Effects of primary reinforcement on pigeons' initial-link responding under a
      concurrent chains schedule with nondifferntial terminal links.
AB  - The effect of primary reinforcement on initial-link responding under concurrent
      chains schedules with nondifferential terminal links was assessed in 12 pigeons.
      The iniitial and terminal links were variable-interval schedules (always the same
      for both alternatives). The positions (left or right key) of the initial-link
      stimuli (red or green) were randomized while the correlation between color and
      food amount remained constant within each condition. The terminal-link stimuli
      were always presented on the center key. Except in two control groups and
      conditions, the terminal-link stimuli were the same color (nondifferential, blue
      or yellow). Over six conditions, the differences in food amont and the durations
      of the initial- and terminal-link schedules were manipulated. In 57 of 60 cases,
      birds generated choice proportions above .50 in favor of the initial-link stimlus
      that was correlated with the larger reinforcer. There was some indication that
      preference increased with shortened terminal-link durations. Because the terminal
      link stimuli were nondifferential, differential responding in the initial links
      cannot be explained easily by conditioned reinforcement represented by the
      terminal-link stimuli. Thus, primiary reinforcement has a direct effect on
      initial-link responding in concurrent-chains schedules.

PMID- 11516117
TI  - Perceptual classes established with forced-choice primary generalization tests
      and transfer of function.
AB  - In Experiment 1, 20 college students learned two identity conditional
      discriminations using squares that differed in interior-fill percentage (called
      Fill23 and Fill77). A two-choice generalization test was then presented with
      number of test trials varied across groups of subjects. The test samples were 19
      squares that ranged in fill value from 23% to 77%; the comparisons were squares
      with Fill23 and Fill77. The resulting gradients did not vary as a function of
      number of test trials. When the generalization test was repeated with a third
      comparison, "neither," the ranges of fill values that occasioned the exclusive
      selection of Fill23 or Fill77 were direct functions of the number of prior two
      choice generalization trials. Finally, a disriminability test revealed that
      Fill23 and Fill77 were disciminable from the intermediate fill values. In
      Experiment 2, perceptual classes were established with 5 new students using 760
      forced-choice generalization test trials. The student were then trained to select
      a different glyph in the presence of Fill23 and Fill77, followed by a three
      choice generalization test in which the 19 fill stimuli served as samples and the
      two glyphs served as comparisons. The gradients ovelapped with those previously
      obtained during the three-choice generalization test that used Fill23 and Fill77
      as comparisons. Finally, a discriminability test showed that many adjacent
      stimuli along thc fill dimension were discriminable from each other. Together,
      the results of both experiments suggest that ranges of fill-based stimuli
      functioned as members of perceptual classes, and each class also functioned as a
      transfer network for a new selection-based response.

PMID- 11516118
TI  - Effect of an implant containing the GnRH agonist deslorelin on secretion of LH,
      ovarian activity and milk yield of postpartum dairy cows.
AB  - Prevention of high plasma progesterone concentrations in the early postpartum
      period may improve fertility. Our objective was to determine whether a Deslorelin
      implant (DESL; 2100 microg, s.c.) would reduce secretion of LH and alter follicle
      dynamics, plasma concentrations of progesterone, estradiol and PGF2alpha
      metabolite (PGFM) in postpartum dairy cows. Cows received DESL on Day 7
      postpartum (Day 7, n=8) or were untreated (Control, n=9). All cows were injected
      with GnRH (100 microg, i.m.) on Day 14 to assess LH response. A protocol for
      synchronization of ovulation with timed AI was initiated on Day 60 (GnRH [Day
      60], CIDR [Day 60 to Day 67], PGF2alpha [Day 67, 25 mg and Day 68, 15 mg], GnRH
      [Day 69] , AI [Day 70]). The LH response to injection of GnRH on Day 14 was
      blocked in animals treated with DESL. Numbers of Class 1 (<6 mm) follicles were
      unaffected (P > 0.05) whereas numbers of Class 2 (6 to 9 mm) (P < 0.01) and Class
      3 (>9 mm) follicles were less (P < 0.01) in DESL cows between Day 7 and Day 21.
      From Day 22 to Day 60, DESL-treated cows had more of Class 1 follicles and less
      Class 2 (P < 0.01) and Class 3 (P < 0.01) follicles, and lower plasma
      concentrations of progesterone and estradiol (P < 0.01). Concentrations of PGFM
      between Day 7 and Day 42 were not affected by treatment (P > 0.05). All cows
      ovulated in response to GnRH on Day 69. Subsequent luteal phase increases in
      plasma progesterone concentrations (Day 70 to Day 84) did not differ. The use of
      the DESL implant associated with PGF2alpha given 14 days later suppressed ovarian
      activity and caused plasma progesterone concentrations to remain < 1 ng/mL
      between Day 22 and Day 51. The DESL implant did not affect milk production.

PMID- 11516119
TI  - A short hypoosmotic swelling test for the prediction of boar sperm fertility.
AB  - This study was designed to explore the relationship between the ejaculate
      response to a hypoosmotic swelling test (HOST) and in vivo fertility in a group
      of 38 boars The hypoosmotic test used was a modification of the HOST that
      involves a shorter incubation time (5 vs 120 min) and lower osmotic pressure (75
      vs 150 mOsm/kg). Ejaculates containing less than 20% abnormal spermatozoa were
      selected and checked for percentage of motility, percentage of normal acrosomes,
      percentage of short ORT and percentage of cells showing positive short HOST
      (sHOST) results Two hundred eightyeight sows were inseminated to obtain in vivo
      fertility and prolificacy data. No differences were shown between technicians in
      the sHOST results obtained. Significant differences were recorded between boars
      in sHOST results (p < 0.002). Only the sHOST result presented a significant
      correlation with in vivo fertility (r = 0.43, p < 0.01). Short HOST data
      significantly improved fertility prediction of routine semen analysis tests.
      Unlike motility and acrosomal status, sHOST values showed a significant decrease
      when fresh ejaculates (37 degrees C) were stored for 24 h at 15 degrees C,
      indicating possible damage due to cold shock.

PMID- 11516120
TI  - Sperm capacitation in vitro in the eld's deer.
AB  - Sperm capacitation was examined in the endangered Eld's deer (Cervus eldi
      thamin). Sperm motility and viability (percentage of sperm cells with intact
      membranes) were assessed in vitro over time after attempting to induce
      capacitation in TALP alone and TALP supplemented with calcium (10 mM CaCl2),
      dibutyryl cAMP (1 mM dbcAMP), or fetal calf serum (20% FCS). Sperm aliquots were
      evaluated at 0, 3, 6, 9, and 12 h for motility, viability, and ability to
      acrosome react after exposure to calcium ionophore (A23187, CI; 10 microM) or
      lysophosphatidylcholine (LC; 100 microg/mL). Fresh sperm aliquots in TALP + 10 mM
      CaCl2 exposed to CI had fewer (P < 0.05) intact acrosomes than the TALP control
      (TALP alone) or dbcAMP and FCS treatments after 9 h. Mean (+/- SEM) percentage of
      intact acrosomes of spermatozoa incubated in medium with increased CaCl2 declined
      (P < 0.05) from 80.2 +/- 2.6% (0 h) to 49.7 +/- 7.3% after prolonged incubation
      (9 h). The proportion of capacitated fresh spermatozoa was not influenced by LC
      treatment. Capacitation was not induced (P > 0.05) by any of the presumptive
      sperm capacitators after freeze-thawing. Likewise, neither CI nor LC induced the
      acrosome reaction (AR) in these spermatozoa, suggesting that the freeze-thawing
      process may have caused membrane damage. Results revealed that the
      supplementation of medium with CaCl2 evokes capacitation in some spermatozoa.
      However, Eld's deer spermatozoa appear remarkably resistant to conventional
      stimulators of capacitation and the AR.

PMID- 11516121
TI  - Retrospective study on an unusual form of ovario-bursal pathology in the camel
      (Camelus dromedarius).
AB  - A peculiar form of ovarian bursa pathology, called hydrobursitis, is described in
      the dromedary camel. This malformation is characterized by a collection of fluid
      within the ovarian bursa with encapsulation of the ovary. Retrospective study of
      all diagnosed cases in our laboratory shows that this malformation is responsible
      for reduced reproductive performance due to abortion, infertility and embryonic
      death. Hydrobursitis was diagnosed in 33 of 355 animals examined. The incidence
      of this lesion was higher in animals that aborted (9/24) or were barren for more
      than 2 years (13/37). Diagnosis by palpation per rectum and ultrasonography, is
      described. Gross pathological and biochemical studies on specimens collected at
      surgery or in the slaughterhouse showed that the fluid is hemorrhagic and that it
      could be a mixture of blood and follicular fluid. Bacteriological and cytological
      studies were inconclusive. The origin of this lesion is discussed in light of
      genetic, pathological and management factors. Loss of embryos in affected animals
      could be due to the effect of increased tension on the uterus caused by the
      accumulation of fluid which ranged in volume from 250 mL to 4240 mL. The
      condition was treated in several females by surgical ablation. Embryo transfer
      was used in females that were bilaterally affected and underwent a bilateral
      ovariectomy. Pregnancy and calving rates were 52.5% and 38.1% for unilaterally
      ovariectomized females bred after surgery and 33.3% and 22.2% for bilaterally
      ovariectomized females used as embryo recipients after surgery. These results
      show that involvement of the uterus in this malformation is very limited and that
      surgery can be considered for valuable animals if they are unilaterally affected.

PMID- 11516122
TI  - Semen plasma proteins prevent cold-shock membrane damage to ram spermatozoa.
AB  - Although the effect of semen plasma on the function of spermatozoa has been
      widely studied, results are contradictory. We showed that semen plasma proteins
      are adsorbed onto the cold-shocked ram sperm surface, and that this adsorption is
      able to reverse the membrane alterations induced by cold-shock. In the present
      study we evaluate whether the addition of semen plasma proteins before the cold
      shock would prevent membrane damage and maintain ram sperm viability. Ram
      spermatozoa freed from semen plasma by a dextran/swim-up procedure were strongly
      affected by the cold-shock treatment, lowering cell viability (membrane integrity
      by fluorescence markers) from 72.2+/-3.4% to 24.6+/-2.1%. Adding semen plasma
      proteins (> 3 kDa) to the medium before the cold treatment had an immediate
      beneficial effect on sperm survival in all samples. This effect was concentration
      dependent, since the percentage of membrane-intact spermatozoa increased
      significantly with increased protein concentration in the incubation medium. The
      highest concentration of proteins (2.1 mg) continued to protect the membranes
      after 1 h of incubation at 20 degrees C while lower concentrations (0.7 and 1.4
      mg) showed a slight decline. Inclusion of linoleic-oleic acids had a beneficial
      effect on preserving sperm viability when 25, 37 or 75 microM linoleic-oleic
      acids were added. There was a positive interaction between fatty acids and semen
      plasma proteins. Thus, the addition of 25 microM oleic-linoleic acid in the
      presence of 2.1 mg semen plasma proteins accounted for an increase in viability
      up to 50.7% significance (P < 0.001) relative to the control sample (25%).
      Likewise, semen plasma proteins significantly promoted the ability of Vitamin E
      (alpha-tocopherol phosphate) to improve sperm survival. A 26% viability value
      obtained after cold-shock in the control sample significantly increased (P <
      0.001) up to 57% in the sample with 1.6 mM Vitamin E phosphate and 2.1 mg semen
      plasma proteins (0 h). This study demonstrates that impaired function of cold
      shocked ram spermatozoa freed from semen plasma could be prevented by addition of
      semen plasma proteins, resulting in higher maintained viability values. Inclusion
      of either linoleic-oleic acids or vitamin E together with semen plasma proteins
      would increase the improvement in ram spermatozoa survival.

PMID- 11516123
TI  - Effect of gonadotrophin dose on oocyte retrieval in superovulated BALB/c mice.
AB  - Mice are commonly used animal models in reproductive and developmental research.
      In order to get satisfying results from such experiments, large numbers of ova
      must be available and this can be achieved by using various ovulation induction
      protocols. To obtain an optimal response from these stimulation protocols,
      parameters such as breeding-housing conditions of the animal strains, the best
      age for superovulation, and type and dose of gonadotrophins must be optimized.
      The aim of this study was to investigate the impact of exogenous stimulation with
      increasing amounts of gonadotrophins on the number and quality of oocytes/pre
      embryos recovered from outbred BALB/c mice. A dose-response analysis was
      performed by stimulating prepubescent (21- to 25-day-old) and sexually mature (6
      to 8 weeks old) female mice with hMG, which contains equal amounts of follicle
      stimulating hormone (FSH) and luteinizing hormone (LH). The stimulation dose
      contained 5, 10, 15, 20, 25 or 30 IU of FSH/LH. The effect of increasing
      stimulation was assessed by monitoring the number and maturity of ova recovered
      from the tubes. The data were analyzed by using a one-way Anova test and student
      t-test. Increasing stimulation doses in the prepubescent females resulted in an
      increased number of ova. A maximum of 55 ova per mouse was reached when
      stimulating with 20 IU of FSH/LH; higher stimulation doses showed no further
      increase in oocyte recovery. In the prepubescent group, a maximal number of
      recovered mature ova was reached with 15 IU of FSH/LH. In the sexually mature
      female group, 20 IU of FSH/LH gave the best quantitative and qualitative results.
      Positive effects of copulation on the number and maturity of oocytes in all
      induction doses were more evident in the prepubescent females and these
      parameters were significantly more improved (P < 0.05) in this group when
      compared to the pubertal females. Our findings led to the conclusion that
      ovulation induction of prepubescent outbred BALB/c mice with 15 IU FSH/LH and
      sexually mature ones with 20 IU FSH/LH give the best results in terms of oocyte
      number and maturity.

PMID- 11516124
TI  - Survival of boar spermatozoa frozen in diluents of varying osmolality.
AB  - We investigated the effects of freezing diluents of differing levels of
      osmolality on boar sperm cryosurvival. The spermatozoa were frozen using a pellet
      technique. Cryosurvival was evaluated in terms of motility, intact acrosomes and
      membrane integrity. The motility parameters were assessed using a computer
      assisted sperm motility analysis (CASA) system. Acrosomal status was monitored by
      means of FITC-labeled peanut agglutinin, and membrane integrity was evaluated
      after double staining with SYBR-14 and propidium iodide. At 3 h of incubation
      after thawing, the highest motility was found in the 420 mOsm/kg group, and
      progressive motiLity in the 420 to 580 mOsm/kg groups was higher than that in the
      hypo- (225 mOsm/kg) and iso-osmotic (290 mOsm/kg) groups (P < 0.05). The intact
      acrosomes of the spermatozoa frozen in the 510 and 580 mOsm/kg BF5 diluents were
      more numerous than in other groups (P < 0.05). The 420 and 510 mOsm/kg groups
      yielded maximal values of post-thaw membrane integrity. These observations
      obtained in the present study indicate that moderately hypertonic BF5 diluents
      are favorable for the cryopreservation of boar spermatozoa.

PMID- 11516125
TI  - Development and viability of in vitro derived porcine blastocysts cultured in
      NCSU23 and G1.2/G2.2 sequential medium.
AB  - Porcine embryo development in vitro is relatively inefficient compared to other
      domestic species. Currently, a single culture medium (NCSU23) is the standard for
      porcine in vitro systems. However, the G1.2/G2.2 sequential culture system has
      been beneficial for embryo development in other species. The objective of this
      study was to compare porcine preimplantation embryo development in vitro and
      subsequent blastocyst viability and metabolic activity using NCSU23 and G1.2/G2.2
      culture media. Oocytes were matured in defined TCM199 base medium for 45 to 47 h
      and fertilized in mTBM for 4 h. Embryos were cultured in either NCSU23 for 146 h
      or G1.2 medium for 72 h followed by culture in G2.2 medium for an additional 74
      h. Blastocyst substrate use was measured using a modification of the hanging drop
      technique. Culture in NCSU23 resulted in a higher percentage (P < 0.05) of embryo
      cleavage (74.0%) and blastocyst development (14.6%) than culture in G1.2/G2.2
      (67.8% and 7.8%, respectively). Both NCSU23 and G1.2/G2.2 produced blastocysts
      with similar mean cell numbers (51.5 +/- 4.3 and 47.1 +/- 4.3, respectively),
      similar glucose use (10.81 +/- 1.39 and 10.12 +/- 1.72 pmol/embryo/3 h,
      respectively) and pyruvate use (1.08 +/- 0.056 and 0.88 +/- 0.048 pmol/embryo/3
      h, respectively). These data indicate that a sequential culture system can
      support porcine embryo development in vitro without compromising embryo
      viability. However, the G1.2/G2.2 system was not as effective as NCSU23 in
      supporting blastocyst development. Sequential media should be formulated
      specifically for porcine embryos to improve embryonic cleavage and blastocyst
      development.

PMID- 11516126
TI  - Systemic relaxin in pregnant pony mares grazed on endophyte-infected fescue:
      effects of fluphenazine treatment.
AB  - Tall fescue is one of the most widely grown forage grasses for horses in the
      United States. However, it is frequently infected with the endophyte Neotyphodium
      coenophialum which produces ergot alkaloids that cause severe adverse effects in
      the pregnant mare. The objectives of this study were to determine the effects of
      fescue toxicosis and fluphenazine on circulating relaxin in pregnant pony mares
      and evaluate the usefulness of relaxin as a monitor of treatment efficacy. Twelve
      mares were maintained on endophyte-infected tall fescue pasture. Group TRT (n =
      6), received 25 mg of fluphenazine decanoate (i.m.) on Day 320 of gestation while
      Group UTRT served as untreated controls. Daily blood samples were collected from
      Day 300 of gestation until Day 3 post partum and analyzed for plasma relaxin
      concentrations using a homologous equine radioimmunoassay. Mean gestation lengths
      were 330 +/- 0.7 and 336.5 +/- 3.2 days for TRT and UTRT mares, respectively (P =
      0.07). Mean plasma relaxin concentrations in both groups of mares during the week
      before treatment (Day 313 to 319) were not different (UTRT, 53.4 +/- 11.3 ng/mL;
      TRT, 61.4 +/- 9.3 ng/mL). In the week after treatment (Day 320 to 326), mean
      plasma relaxin tended to be higher (P = 0.1) in TRT mares (66.7 +/- 6.2 ng/mL)
      when compared with UTRT mares (49.6 +/- 6.6 ng/mL), representing a 17.1 ng/mL
      difference in circulating relaxin between the two groups. Systemic relaxin during
      the last week before delivery (days relative to parturition) for UTRT and TRT
      mares was 45.7 +/- 6.7 and 64.7 +/- 6.4 ng/mL (P = 0.06), respectively. At Day -8
      and Day -5 relative to parturition, systemic relaxin in TRT mares was
      significantly higher (P < 0.05) than in UTRT mares. Three of the six UTRT mares
      and one TRT mare showed clinical symptoms of fescue toxicosis. In the week before
      delivery, circulating relaxin in mares with problematic pregnancies (39.9 +/- 7.8
      ng/mL) was significantly lower than concentrations measured in mares with normal
      pregnancies (63.4 +/- 5.4 ng/mL; P = 0.03). Clinical observations suggest that a
      one-time injection with fluphenazine improved pregnancy outcome by reducing the
      adverse effects of fescue toxicosis concomitant with a stabilization of plasma
      relaxin concentrations. These data support the hypothesis that systemic relaxin
      may be a useful biochemical means of monitoring placental function and treatment
      efficacy in the mare.

PMID- 11516127
TI  - Semen characteristics after vasectomy in the ram.
AB  - The objective of this study was to monitor the changes in semen characteristics
      in vasectomized rams and to determine if infertility was present 14 days after
      vasectomy. Experiments were performed using five cross-breed rams, aged between
      18 and 30 months. Semen was collected weekly by artificial vagina from 2 months
      before to 5 months after vasectomy. After sexual rest for 10 days, vasectomy was
      performed by the cranial midscrotal approach. In all ejaculates the volume,
      concentration, total sperm number, motility and morphology (normal spermatozoa,
      loose heads) were determined and sperm viability (SYBR-14/PI) was evaluated in
      all semen samples collected after vasectomy. In the first ejaculate obtained 14
      days post vasectomy all rams showed a significant (P < 0.05) drop in mean volume
      (from 1.2 to 0.5 mL), total sperm count (from 5176.8 to 51.1 x 10(6)) and
      morphologically normal sperm (from 84.1 to 15.7%), when compared to the last
      prevasectomy collection. We could also demonstrate a positive correlation (r =
      0.89) between the individual cumulative total number of spermatozoa after
      vasectomy and the scrotal circumference measured before vasectomy. Sperm motility
      and viability could never be demonstrated after vasectomy and normal spermatozoa
      continuously decreased concomitant with an increase in loose heads. On post
      mortem examination 5 months after surgery, spermatocele formation and multiple
      sperm granulomas were present in all five rams. Our results show that in the
      first ejaculate collected by artificial vagina 14 days after vasectomy, no motile
      and viable spermatozoa could be detected. Despite weekly collections during a 5
      month period after sterilization, azoospermia could never be achieved.

PMID- 11516128
TI  - Attenuation of premature estrous behavior in postpartum beef cows synchronized to
      estrus using GnRH and PGF2alpha.
AB  - The efficacy of GnRH and PGF2alpha (7-day injection interval) for estrus
      synchronization is diminished by estrous expression before PGF2alpha (premature
      estrus; PE). Effects of modifications to GnRH-PGF2alpha protocols on the
      incidence of PE and other indicators of reproductive performance were evaluated.
      In Experiment 1, Angus-based crossbred cows (n=51) received 25 mg of PGF2alpha
      i.m. on Day 0. Animals were randomly assigned by parity and interval postpartum
      to receive GnRH 100 microg i.m. on either Day -7 or Day -6. Estrous detection and
      AI were conducted from Day -3 to Day 5. Treatment had no effect on the incidence
      of PE, estrous response, conception rate per AI or synchronized pregnancy rate (6
      vs. 7-day interval; 8 vs. 15%; 92 vs. 93%; 77 vs. 76%; 71 vs. 70%,
      respectively). In Experiment 2, Angus cows (n=150) received GnRH 100 microg i.m.
      on Day -7 and 25 mg PGF2alpha i.m. on Day 0. Animals were randomly assigned by
      parity, interval postpartum, and body condition score to receive either no
      further treatment (Control) or 0.5 mg melengestrol acetate/hd/d from Day -7 to
      Day -1 (MGA). Estrous detection and AI were conducted from Day -2 to Day 7. Fewer
      (P < 0.05) MGA-treated cows were detected in PE (0%) compared to controls (7%).
      Treatment had no effect on estrous response or synchronized pregnancy rates
      (Control vs. MGA; 78 vs. 84%; 52 vs. 60%, respectively). Conception rate per AI
      of cows > or = 60 days postpartum were not affected by treatment (Control vs.
      MGA; 79 vs. 73%) however, control cows < 60 days postpartum tended (P < 0.10) to
      have lower conception rates per AI (39%) than did their MGA-treated counterparts
      (69%). In summary, 6- and 7-day GnRH-PGF2alpha injection intervals resulted in
      similar synchronized reproductive performance. Inclusion of MGA feeding between
      GnRH and PGF2alpha injections eliminated the occurrence of premature estrus and
      improved conception rate per AI of late-calving cows.

PMID- 11516129
TI  - Comparisons of oocyte maturation times and of three methods of sperm preparation
      for their effects on the production of goat embryos in vitro.
AB  - Various times of in vitro maturation of oocytes, and three methods of separating
      spermatozoa from frozen-thawed semen (Percoll density-gradient centrifugation,
      swim-up, and glass-wool filtration), were compared for their effects on goat
      embryo production in vitro. Cumulus-oocyte-complexes (COCs) from abattoir ovaries
      were matured in M199 supplemented with 10% fetal calf serum and hormones. In
      Experiment 1, COCs were fixed at 4 h intervals from 0 to 27 h of culture to
      assess oocyte nuclear maturation. A higher proportion cultured for 27 h than for
      24 h were in Metaphase II (27/37, 73% vs. 18/33, 55%, P < 0.05). In Experiment 2,
      the effects of separation methods on total numbers and numbers of membrane-intact
      spermatozoa, and the acrosome reaction were compared. Total numbers after Percoll
      density-gradient centrifugation were approximately 4 times higher than after swim
      up and approximately 2 times higher than after glass-wool filtration (P < 0.001).
      Progression of the acrosome reaction was not affected differentially. In
      Experiments 3 and 4, after 27 h of culture the COCs were inseminated with sperm
      isolated by the three methods. In Experiment 3, presumptive zygotes were examined
      for pronucleus (PN) formation at 6, 12, 18 and 24 h post-insemination. At 12 h,
      male PN formation rate from Percoll-treated spermatozoa was higher than from
      sperm subjected to swim-up and glass-wool treatments (20/37, 54% vs. 6/37, 16%
      and 6/38, 16%, respectively; P < 0.001). In Experiment 4, embryos were compared
      for cleavage at 48 h and development into blastocysts, hatching rates and cell
      number at 192 h. The rates of cleavage and blastocyst formation in the Percoll
      treated group were higher (P < 0.05) than in the swim-up and glass-wool groups
      (62% and 18% vs. 50% and 11%, and 45% and 8%, respectively). Similarly, the mean
      cell number in the Percoll group was higher (P < 0.05) than in the swim-up and
      glass-wool groups (167 +/- 5 vs. 149 +/- 4 and 126 +/- 4, respectively). We
      conclude that Percoll density-gradient centrifugation is superior to the other
      two methods for separating goat spermatozoa from frozen-thawed semen in
      preparation for IVF.

PMID- 11516131
TI  - Selected air quality trends and recent air pollution investigations in the US
      Mexico border region.

PMID- 11516130
TI  - Mixing science with false statements.

PMID- 11516132
TI  - Meteorological simulations of boundary-layer structure during the 1996 Paso del
      Norte Ozone Study.
AB  - Meteorological simulations centered around the border cities of El Paso and
      Ciudad Juarez have been performed during an ozone episode that occurred on August
      13, 1996 during the 1996 Paso del Norte Ozone Study field campaign. Simulations
      were performed using the HOTMAC boundary-layer meteorological model using a 1, 2,
      4 and 8-km horizontal grid size nested mesh system. Investigation of the vertical
      structure and evolution of the atmospheric boundary layer for the August 12-14
      time period is emphasized in this paper due to its suspected importance in
      precipitating the ozone episode [Sci Total Environ (2001)]. This period was
      characterized by a slowly-evolving high pressure system over the region, a
      persistent upper-level jet at 2500-3500 m above ground level (agl), deep daytime
      mixed layer heights of 3500 m depth and unusually deep nighttime stable layers
      extending up to 2500 m above the ground. The fact that the boundary-layer growth
      stalled on the morning of August 13 relative to that on August 12 has been
      suggested as a possible reason for the ozone episode on the 13th. In addition,
      relatively weak surface-level winds were measured on August 13. Using both model
      results and experimental data we hypothesize explanations for the slower mixed
      layer growth on the morning of the 13th and the stronger surface-level winds
      found on the 12th and 14th.

PMID- 11516133
TI  - Compilation and evaluation of a Paso del Norte emission inventory.
AB  - Emission inventories of ozone precursors are routinely used as input to
      comprehensive photochemical air quality models. Photochemical model performance
      and the development of effective control strategies rely on the accuracy and
      representativeness of an underlying emission inventory. This paper describes the
      tasks undertaken to compile and evaluate an ozone precursor emission inventory
      for the El Paso/Ciudad Juarez/Southern Dona Ana region. Point, area and mobile
      source emission data were obtained from local government agencies and were
      spatially and temporally allocated to a gridded domain using region-specific
      demographic and land-cover information. The inventory was then processed using
      the US Environmental Protection Agency (EPA) recommended Emissions Preprocessor
      System 2.0 (UAM-EPS 2.0) which generates emissions files compatible with the
      Urban Airshed Model (UAM). A top down evaluation of the emission inventory was
      performed to examine how well the inventory represented ambient pollutant
      compositions. The top-down evaluation methodology employed in this study compares
      emission inventory ratios of non-methane hydrocarbon (NMHC)/nitrogen oxide (NOx)
      and carbon monoxide (CO)/NOx ratios to corresponding ambient ratios. Detailed
      NMHC species comparisons were made in order to investigate the relative
      composition of individual hydrocarbon species in the emission inventory and in
      the ambient data. The emission inventory compiled during this effort has since
      been used to model ozone in the Paso del Norte airshed (Emery et al., CAMx
      modeling of ozone and carbon monoxide in the Paso del Norte airshed. In: Proc of
      Ninety-Third Annual Meeting of Air & Waste Management Association, 18-22 June
      2000, Air & Waste Management Association, Pittsburgh, PA, 2000).

PMID- 11516134
TI  - Hydrocarbon source apportionment for the 1996 Paso del Norte Ozone Study.
AB  - The 1996 Paso del Norte (PdN) ozone study was conducted to improve current
      understanding of the significant meteorological and air quality processes that
      lead to high concentrations of ozone in El Paso, Texas (USA) and Ciudad Juarez,
      Chihuahua (Mexico). Two-hour canister samples were collected five times daily at
      05.00-07.00 h, 07.00-09.00 h, 09.00-11.00 h, 11.00-13.00 h, and 15.00-17.00 h MST
      during intensive study periods at one urban and one rural site on each side of
      the border. An automated gas chromatograph was operated at one site in central El
      Paso. Source profiles (the fractional chemical composition of emissions) from
      motor vehicles, gasoline, liquefied petroleum gas, and commercial natural gas
      were combined with source profiles from other studies for input to the Chemical
      Mass Balance (CMB) receptor model to apportion the measured non-methane
      hydrocarbons (NMHC) to sources. On-road vehicle emissions accounted for one-half
      to two-thirds of the NMHC in Ciudad Juarez and El Paso with the highest
      contributions occurring during the morning and afternoon commute periods.
      Emissions from diesel exhaust contributed approximately 2-3% of NMHC in Ciudad
      Juarez and less than 2% in El Paso. The average sum of liquid gasoline and
      gasoline vapor increased during the day in Ciudad Juarez from 2% at 06.00 h to
      approximately 12% at 16.00 h. Diurnal and day-of-the-week patterns in the liquid
      gasoline contributions are essentially identical to the corresponding patterns
      for motor vehicle exhaust, which suggest that a large fraction of the liquid
      gasoline contribution may be associated with tailpipe emissions rather than
      evaporative emissions from motor vehicles or industrial sources. Including the
      sum of the two sources put the upper limit for tailpipe contributions at 60-70%
      of NMHC.

PMID- 11516135
TI  - Back-trajectory analyses of fine particulate matter measured at Big Bend National
      Park in the historical database and the 1996 scoping study.
AB  - Analyses of the sources of fine particles associated with visibility reduction at
      Big Bend National Park during a 10-year period from 1989-1998 and from a regional
      visibility scoping study conducted during September and October 1996 at 19 sites
      in Texas and Mexico are summarized and compared. Fine sulfate particles are the
      largest fraction of the fine mass, and scattering by sulfates is estimated to be
      nearly half of the non-Rayleigh light extinction at Big Bend. Fine particulate
      sulfur concentrations are seasonal, with the highest values occurring during the
      summer and fall when back trajectory analyses show that air masses are most
      likely to arrive at Big Bend from the southeast after passing over Mexico or from
      areas to the northeast including east Texas. Episodically, high concentrations of
      fine mass and high light extinction values can be due to other species such as
      fine organic carbon or blowing soil dust. Organic carbon concentrations are often
      extremely high during the spring, especially during May. A combination of back
      trajectory analyses and the coincidence of high organic carbon and high non-soil
      potassium concentrations leads to the hypothesis that these concentrations are
      due to fires, primarily seasonal agricultural burning in Mexico and Central
      America. Fine soil concentrations often reach values that are twice the annual
      mean during July. These concentrations also frequently have high Al/Ca ratios,
      indicative of Saharan dust. Back trajectories associated with these events show
      air masses arriving from the southeast and are consistent with the hypothesis of
      transport of air masses from Africa during July. There is a high frequency of
      transport of air masses from Mexico to Big Bend, especially during the summer
      when fine mass concentrations and light extinction are highest. Therefore,
      sources and potential sources of sulfates and other fine particles in Mexico,
      particularly in areas southeast of the park have a high likelihood of
      contributing to visibility degradation at the park. Source areas to the northeast
      of the park, in east Texas and farther upwind also contribute to high fine
      sulfate concentrations.

PMID- 11516136
TI  - Volatile organic compound measurements in the California/Mexico border region
      during SCOS97.
AB  - Measurements of volatile organic compounds (VOC) were carried out in the
      California/Mexico border region during the Southern California Ozone Study in the
      summer of 1997 (SCOS97). Integrated 3-h samples were collected in Rosarito (south
      of Tijuana, Mexico) and in Mexicali during intensive operational periods (IOP),
      twice per IOP day. VOC were collected using stainless-steel 6-1 canisters;
      carbonyl compounds were collected using 2,4-dinitrophenyl-hydrazine (DNPH)
      impregnated C18 SepPak cartridges. The canister samples were analyzed for
      speciated volatile hydrocarbons (C2-C12), CO, CO2, CH4, methyl t-butyl ether
      (MTBE), and halogenated hydrocarbons. DNPH-impregnated cartridges were analyzed
      for 14 C1-C7 carbonyl compounds. The concentrations of all species were higher at
      Mexicali than in Rosarito. A good correlation between total non-methane
      hydrocarbons (TNMHC), CO, and other pollutants associated with motor vehicle
      emissions observed for Mexicali indicates that the main source of TNMHC at this
      site is vehicular traffic.

PMID- 11516137
TI  - Techniques to assess cross-border air pollution and application to a US-Mexico
      border region.
AB  - A year-long assessment of cross-border air pollution was conducted in the
      eastmost section of the US-Mexico border region, known as the Lower Rio Grande
      Valley, in South Texas. Measurements were conducted on the US side and included
      fine particle mass (PM2.5) and elemental composition, volatile organic compounds
      (VOCs) and meteorology. Wind sector analyses of chemical tracers and diagnostic
      ratios, in addition to principal component analysis (PCA), were initially applied
      to assess cross-border and overall air shed influences. Linear-angular
      correlation statistics [Biometrika, 63, (1976), 403-405] and nonparametric
      multiple comparisons between wind sectors were computed with the particle element
      data using principal component scores from PCA to determine the direction of
      source classes. Findings suggest crustal particles and salts carried or stirred
      by sea breeze winds from a southerly and southeasterly direction from the Gulf of
      Mexico heavily influenced the elemental composition of the particulate samples.
      Pair-wise comparisons of wind directions for the principal component scores
      suggest possible oil combustion influences from utilities or boilers coming from
      the south and possible coal combustion influences from the north and northwest.
      The techniques discussed can provide a methodology to assess future ambient
      levels and cross-border influences in the Valley as conditions change.

PMID- 11516138
TI  - Source characterization of major emission sources in the imperial and Mexicali
      Valleys along the US/Mexico border.
AB  - Chemical profiles for particle emissions are needed for source apportionment
      studies using the chemical mass balance (CMB) receptor model. Source measurements
      of geological sources, motor vehicle exhaust, vegetative burning (e.g. asparagus,
      field burning, charbroil cooking), and industrial sources (e.g. oil-fueled glass
      plant, manure-fueled power plants) were acquired as part of the Imperial/Mexicali
      Valley Cross Border PM10 Transport Study in 1992. Six different source sampling
      techniques (i.e. hot- and diluted-exhaust sampling, ground-based source sampling,
      particle sweeping/grab sampling, vacuum sampling, and laboratory resuspension
      sampling) were applied to acquire filter samples of PM 2.5 and PM10 (particulate
      matter with aerodynamic diameters < 2.5 and 10 microm, respectively). Filter
      samples were analyzed for mass by gravimetry, elements (Na to U) by X-ray
      fluorescence, anions (Cl(-), NO3(-), SO4(=)) by ion chromatography, ammonium
      (NH4(+)) by automated colorimetry, soluble sodium (Na+) and potassium (K+) by
      atomic absorption spectrophotometry, and organic and elemental carbon (OC, EC) by
      thermal/optical reflectance. Concentration data were acquired for a total of
      approximately 50 chemical species. Elevated abundances of crustal components (Al,
      Si, K, Ca, Fe) from geological material, carbon (OC, EC) and trace elements (Br,
      Pb) from vehicle exhausts, carbon (OC, EC) and ions (K(+), Cl(-)) from vegetative
      burning, ions (SO4(=), NH4(+), Na(+), K(+), Cl(-)) and elements (Cl, Se) from a
      manure-fueled power plants, and sulfur and trace elements (Na(+), Pb, Se, Ni, V)
      from an oil-fueled glass plant were found in the resulting source profiles.
      Abundances of crustal species (e.g. Al, Si, Ca) in the Imperial/Mexicali Valley
      geological profiles are more than twice those found in central and southern
      California. Abundances of lead in motor vehicle exhausts indicate different
      vehicle fleets in border cities. Emission profiles from field burning and
      charbroil cooking specific to the border area show that a majority (>60%) of
      emissions are comprised of carbon, with high organic to total carbon ratios (0.93
      to 0.97). Abundances of sulfate and ammonium account for nearly 60% of the manure
      fueled power plant's emissions. Elevated levels of metals (Na(+), Pb, Cd, Se) and
      byproducts of petroleum combustion (S, Ni, V) were found in the oil-fueled glass
      plant's emissions.

PMID- 11516139
TI  - Zones of representation for PM10 measurements along the US/Mexico border.
AB  - The 'Imperial/Mexicali Valley Cross-Border PM10 Transport Study' acquired a
      database of meteorological and air quality measurements to determine source
      contributions to elevated PM10 concentrations and to estimate transport of PM10
      between the US and Mexico. The study was conducted from 13 March 1992 to 29
      August 1993, in a 80-km long by 20-km wide area spanning the US/Mexico border
      approximately 200 km inland from the coast of the Pacific Ocean, with monitoring
      sites located in the Imperial Valley on the US side and in the Mexicali Valley on
      the Mexico side. Measurements of PM 10 (particles with aerodynamic diameters less
      than 10 microm) mass, elements, water-soluble cations (i.e. sodium, potassium,
      ammonium) and anions (i.e. chloride, nitrate, sulfate), organic and elemental
      carbon and particle light absorption were acquired at two base sites on an every
      sixth-day schedule supplemented by daily monitoring during winter and 4 times per
      day monitoring during intensive periods. Measurements were also taken at as many
      as 30 neighborhood (satellite) sites during week-long intensive monitoring
      periods in spring, summer and winter. This paper examines the zones of
      representation of long-term PM10 monitors by comparing their measurements with
      those from a spatially dense network of satellite sites. PM10 concentrations at
      the Mexicali site were consistently 30 to 50% higher than those observed at the
      Calexico site, even though the two sites were only 12 km apart. Distinct diurnal
      variations were found, with 6-h average PM10 concentrations often varying by a
      factor of 2 throughout the day - lowest during afternoon (12.00-18.00 h PST) and
      highest during night time (18.00-24.00 h PST). On average, crustal material
      accounted for 32-35% of annual-average PM10, carbonaceous aerosol for 20-30%, and
      ionic species for 8-10%. Levels of trace elements and sea salt were in the range
      of 1-4% of PM10. Significant concentration variations were found within the study
      area. PM10 concentrations in Mexico were double those in the US, decreasing with
      increasing northerly distance.

PMID- 11516140
TI  - Potential particulate impacts at the Grand Canyon from northwestern Mexico.
AB  - Project MOHAVE was a major air quality and visibility research program conducted
      from 1990 to 1999 to investigate the causes of visibility impairment in the Grand
      Canyon National Park region. At Meadview, a remote monitoring site just west of
      the Grand Canyon National Park, on September 1 and 2, 1992, the concentrations of
      sulfate (3.1 and 4.3 microg sulfate/m3) were the highest seen in 6 years of
      monitoring at this site. During this period, the concentrations of SO2 at
      Meadview were also abnormally high and approximately three times the sulfate
      concentrations, on a nmol/m3 basis. High concentrations of sulfate and SO2
      extended south into southern Arizona and northwestern Mexico. Based on ambient
      atmospheric conditions, emissions from the Mohave Power Project (MPP) 110 km
      upwind of Meadview could not have been responsible for the majority of the
      regionally observed sulfur oxides. The geographical distribution of SO2 and
      sulfate, and available source information suggest that northwestern Mexico was a
      significant source of the unusually high observed sulfur oxides. A CMB model
      developed during Project MOHAVE was used to apportion sulfur oxides at Meadview
      and other sampling sites throughout the study region for August 31-September 2,
      1992. The results indicate that the contribution of MPP to sulfate at Meadview
      was typical. However, the transport of SOx from northwestern Mexico was elevated
      throughout much of the region during this time period. This led to the large
      increase in sulfate concentrations at Meadview on September 1 and 2. These
      results indicate that emissions from Mexico can be a significant source of
      particulate material in the Grand Canyon.

PMID- 11516141
TI  - Preliminary assessments of spatial influences in the Ambos Nogales region of the
      US-Mexican border.
AB  - Ambient air measurements collected from 1994 to 1995 were used in a preliminary
      assessment of potential source and spatial influences in the Ambos Nogales border
      region (Nogales, Arizona, USA and Nogales, Sonora, Mexico). In this assessment,
      volatile organic compounds (VOC) and particulate matter (PM) species were used
      from four sites, two on either side of the border. An examination of median
      levels and principal component analysis indicated the dominance of soil dusts and
      mobile sources. Pairwise comparisons of sites for VOCs associated with mobile
      sources revealed statistically significant differences between sites in the
      central Nogales area vs. the two sites furthest from the border. Particulate lead
      at Mexican sites was higher and significantly different vs. US sites. Although
      further analyses are necessary, findings suggest that local and immediate
      mobile/other anthropogenic and soil dust influences are present throughout
      Nogales, with particulate lead from leaded motor vehicle exhaust or soldering
      operations being a possible influence on the Mexican side.

PMID- 11516142
TI  - The 1996 Paso del Norte Ozone Study: analysis of meteorological and air quality
      data that influence local ozone concentrations.
AB  - The 1996 Paso del Norte Ozone Study and subsequent data analyses were implemented
      to develop an understanding of the chemical and physical processes which lead to
      high concentrations of ozone in the Paso del Norte study area which includes El
      Paso County, Texas, Sunland Park, New Mexico, and Ciudad Juarez, Mexico. Both the
      data and data analysis results are being used to support photochemical grid
      modeling. El Paso County and Sunland Park fail to meet the National Ambient Air
      Quality Standard (NAAQS) for ozone, and neighboring Ciudad Juarez fails to meet
      the Mexican ambient standard for ozone. This paper summarizes the measurement
      campaigns of the 1996 Paso del Norte Ozone Study and the findings and conclusions
      that arose from subsequent data analyses. Data analyses showed that high ozone
      concentrations resulted from a combination of conditions, including high surface
      temperatures, strong sunlight with few clouds, light surface winds and high
      concentrations of ozone precursors at ground level in the morning, and slow
      convective boundary layer (CBL) growth. Synoptic-scale meteorological conditions
      observed during high ozone episodes included an aloft high-pressure system and
      aloft warming. Aloft carryover of ozone and ozone precursors did not
      significantly contribute to high concentrations of ozone at the surface.

PMID- 11516143
TI  - Signaling through the CLAVATA1 receptor complex.

PMID- 11516144
TI  - Plant development going MADS.
AB  - It has been known for a decade that the plant MADS genes are important regulators
      of meristem and floral organ identity. The MADS family in Arabidopsis consists of
      more than 80 members and, until recently, the function of the majority of these
      genes was unknown. With the enhanced ability to generate loss-of-function mutants
      and overexpression lines, the function of the MADS gene family members is
      beginning to be elucidated. Recent progress demonstrates that MADS genes in
      Arabidopsis are important regulators not only of meristem and floral organ
      identity but also of flowering timing and cell-type specification in floral
      organs.

PMID- 11516145
TI  - Differential induction of two potato genes, Stprx2 and StNAC, in response to
      infection by Phytophthora infestans and to wounding.
AB  - To find out more about the interaction between potato and Phytophthora infestans
      at the molecular level, we screened for genes induced early after infection using
      mRNA differential display. Among the twenty cDNA clones recovered in the screen,
      two were found to represent plant genes whose transcript levels increased during
      infection of intact plants. These two genes differed strikingly in their response
      to wounding. Stprx2, a putative peroxidase, responded slowly and transiently to
      wounding, and its expression pattern was similar to that of gst1, a well
      described pathogen-induced gene of potato. The second gene, StNAC, was induced
      rapidly and strongly after wounding but not systemically. Transcript levels
      reached a maximum after around 1 h and returned to basal levels after ca. 24 h.
      StNAC has strong similarity to the ATAF subfamily of NAC domain proteins, a large
      family of putative transcriptional activators. Arabidopsis ATAF1 and ATAF2 were
      also shown to be induced by wounding. This implies that the ATAF genes are not
      merely structurally similar but also share a conserved role in stress responses.

PMID- 11516146
TI  - Identification of pronp1, a tobacco profilin gene activated in tip-growing cells.
AB  - In plant cells, several cellular processes depend on rapid reorganization of a
      dynamic network of actin cytoskeletal elements in response to internal and
      environmental stimuli. Profilins, ubiqitous eukaryotic actin monomer-binding
      proteins with highly conserved three-dimensional structures, regulate the actin
      cytoskeleton and are considered to link the microfilament system with signal
      transduction pathways. Plant profilins have been grouped into two distinct
      classes, gametophytic (pollen-specific) and sporophytic. Here we report the
      isolation of a profilin gene that seems to be activated during tip growth of
      specialized cells of gametophytic as well as sporophytic origin. Identification
      of a genomic DNA clone containing a tobacco profilin gene, pronp1, and analysis
      of the pronp1 promoter-uidA fusion gene in transgenic Nicotiana tabacum plants
      revealed a prominent expression of pronp1 in mature pollen and elongating pollen
      tubes and significant activity in root hairs of developing seedlings. This
      expression pattern was distinct from that of any other profilin gene isolated so
      far. Pronp1 thus represents a unique profilin gene that is activated at the
      transcriptional level in two kinds of tip-growing cells, pollen tubes and root
      hairs, both of which require rapid organization of the actin cytoskeleton. The
      isolation of such a gene has fundamental importance for our understanding of
      modulation of the actin cytoskeleton at the molecular level.

PMID- 11516147
TI  - Photoaffinity labelling with the cytokinin agonist azido-CPPU of a 34 kDa peptide
      of the intracellular pathogenesis-related protein family in the moss
      Physcomitrella patens.
AB  - As in higher plants, the development of the moss Physcomitrella patens is
      regulated by environmental signals and phytohormones. At the protonema level
      transition from chloronema to caulonema cells is under auxin control. The
      formation on second sub-apical caulonema cells of buds that will give rise to the
      leafy gametophore requires cytokinins. Using [3H]azidoCPPU (1-(2-azido-6
      chloropyrid-4-yl)-3-(4-[3H])phenylurea), a photoactivatable cytokinin agonist, we
      have specifically photolabelled a soluble 34 kDa protein of P. patens. Urea
      derivatives were very efficient competitors of photolabelling while purine-type
      cytokinins were poor competitors. The protein UBP34 was purified by affinity
      chromatography and the sequences of six internal peptides obtained. A cDNA
      encoding UBP34 was cloned by screening a P. patens protonema cDNA library with a
      probe amplified by PCR using degenerate primers designed from the peptide
      sequences. The UBP34 amino acid sequence shows an average sequence identity of
      42% with both intracellular PR proteins and the BetV1-related family of plant
      allergens. Recombinant UBP34 expressed in Escherichia coli was confirmed to bind
      azidoCPPU.

PMID- 11516148
TI  - Methylation of the Opaque2 box in zein genes is parent-dependent and affects O2
      DNA binding activity in vitro.
AB  - In the maize endosperm, the expression of the subfamily 4 (SF4) of the zein genes
      is under the transcriptional control of the Opaque2 (O2) basic leucine zipper
      transcriptional activator, which binds to the O2-box 5'-TCCACGTAGA-3'. Southern
      experiments showed that the O2-box core sequence ACGT is heavily methylated in
      sporophytic tissues but becomes hypomethylated in the endosperm. DNA analyses of
      two inbred lines and their reciprocal crosses indicate that the hypomethylation
      state is established on the maternal complements of the endosperm.
      Electrophoretic mobility shift assay (EMSA) and southwestern experiments with
      endosperm protein extracts and recombinant O2 using oligonucleotides with
      methylated and unmethylated cytosines in the O2-box indicate an inhibitory effect
      of modified sequences on O2-binding activity. These results suggest that DNA
      methylation modulates O2 activity in vivo and shed light on molecular mechanisms
      involved in the parent-dependent zein gene expression in maize endosperm.

PMID- 11516149
TI  - Single-copy primary transformants of maize obtained through the co-introduction
      of a recombinase-expressing construct.
AB  - We describe a variation of the method to generate single-copy transgenic plants
      by recombinase-mediated resolution of multiple insertions. In this study, a
      transgene construct flanked by oppositely oriented lox sites was co-bombarded
      into maize cells along with a cre-expressing construct. From analysis of the
      regenerated plants, a high percentage of the primary transformants harbored a
      single copy of the introduced transgene, and among these, a majority also lacked
      the cre construct. We deduce that the expression of cre must have contributed to
      resolving concatemeric molecules either prior to or after DNA integration into
      the maize genome.

PMID- 11516150
TI  - The expression of Brostm, a KNOTTED1-like gene, marks the cell type and timing of
      in vitro shoot induction in Brassica oleracea.
AB  - We studied the early events of de novo formation of adventitious shoot meristems
      in stem segments of Brassica oleracea. A regeneration system was used that is
      efficient, rapid, highly responsive to cytokinins and does not involve callus
      formation, thus allowing studies on a direct developmental switch of cells in the
      stem segment to form adventitious shoot meristem cells. Shoot meristem cells and
      dividing cells were marked from very early stages using in situ hybridization
      studies with Brostm, a Brassica homologue of the Arabidopsis SHOOTMERISTEMLESS
      (STM) gene, and a cyclin box-derived probe, Brocyc, respectively. We show that
      the process of developmental switching starts before any cell division occurs in
      the stem explants. This switching occurs synchronously both longitudinally and
      transversely in the explant, in groups of 5-7 phloem parenchyma cells subtending
      vascular bundles in the explant. Brostm is induced specifically in response to a
      cytokinin, benzyladenine, within 4 h of treatment and the transcripts persist
      during cell proliferation leading to shoot differentiation. We also show that
      during adventitious shoot formation, cells expressing Brostm are distinct from
      those expressing Brocyc. Lastly, our data suggest that, although developmental
      switching is initiated synchronously within 4 h of treatment, it requires 8 h of
      treatment for the establishment of organogenic determinance. The latter process
      is aynchronous, implying that additional factors formed later than Brostm are
      required to achieve maximal levels of determined cell populations to form
      adventitious shoots in vitro.

PMID- 11516151
TI  - Impaired growth in transgenic plants over-expressing an expansin isoform.
AB  - Expansins are cell wall proteins characterised by their ability to stimulate wall
      loosening during cell expansion. The expression of some expansin isoforms is
      clearly correlated with growth and the external application of expansins can
      stimulate cell expansion in vivo in several systems. We report here the
      expression of a heterologous expansin coding sequence in transgenic tomato plants
      (Lycopersicon esculentum Mill.) under the control of a constitutive promoter. In
      some transgenic lines with high levels of expansin activity extractable from cell
      walls, we observed alterations of growth: mature plants were stunted, with
      shorter leaves and internodes, and dark-grown seedlings had shorter and wider
      hypocotyls than their wild-type counterparts. Examination of hypocotyl sections
      revealed similar differences at the cellular level: cortical and epidermal cells
      were shorter and wider than those from wild-type seedlings. The observed
      stimulation of radial expansion did not compensate for the decreased elongation,
      and overall growth was reduced in the transgenics. As this observation can seem
      paradoxical given the known effect of expansins on isolated cell walls, we
      examined the mechanical behaviour of transgenic tissue. We measured a decrease in
      hypocotyl elongation in response to acidic pH in the transformants. This result
      may account for the alterations in cell expansion, and could itself be explained
      by a reduced susceptibility of transgenic cell walls to expansin action.

PMID- 11516152
TI  - Molecular characterization of StCDPK1, a calcium-dependent protein kinase from
      Solanum tuberosum that is induced at the onset of tuber development.
AB  - We isolated a full-length cDNA clone (StCDPK1) encoding a calcium-dependent
      protein kinase (CDPK) by screening a stolon tip cDNA library from potato plants
      (Solanum tuberosum L.). The predicted amino acid sequence of the cDNA reveals a
      high degree of similarity with other members of the CDPK family except in the N
      terminal region. As described for other CDPKs, StCDPK1 has a putative N-terminal
      myristoylation sequence. A coupled transcription/translation system was used to
      demonstrate that this post-translational modification occurs in vitro. The
      behaviour of the myristoylated form of StCDPK1 during its purification on a
      phenyl-Sepharose column mimics that of the endogenous potato enzyme suggesting
      that this modification occurs in vivo. In addition, a possible palmitoylation
      site is present in StCDPK1. Southern blot analysis suggests that more than one
      CDPK isoform is present in potato plants. Northern blot analysis of steady-state
      mRNA levels for StCDPK1 in different tissues of potato plants shows that the
      transcript is differentially expressed in tuberizing stolons. The transcript
      appears in the early steps of tuber formation before the induction of other
      genes, such as Pin2 and patatin. This result parallels previous data on CDPK
      activity in potato plants which was highest at the beginning of tuberization. Our
      results suggest that StCDPK1 is developmentally regulated. The early and
      transient expression of this CDPK isoform in the tuberization process suggests
      that this kinase could trigger a cascade of phosphorylation events involved in
      tuber induction.

PMID- 11516153
TI  - A combination of the F-box motif and kelch repeats defines a large Arabidopsis
      family of F-box proteins.
AB  - In the sequences released by the Arabidopsis Genome Initiative (AGI), we have
      discovered a new large gene family (48 genes as of July 2000). A detailed
      computational and biochemical analysis of the predicted gene products reveals a
      novel family of plant F-box proteins, where the amino (N)-terminal F-box motif is
      followed by four kelch repeats and a characteristic carboxy-terminal domain. F
      box proteins are an expanding family of eukaryotic proteins, which have been
      shown in some cases to be critical for the controlled degradation of cellular
      regulatory proteins via the ubiquitin pathway. The F-box motif of the At5g48990
      gene product, a member of the family, was shown to be functionally active by its
      ability to mediate the in vitro interaction between At5g48990 and ASK1 proteins.
      F-box proteins specifically recruit the targets to be ubiquitinated, mainly
      through protein-protein interaction modules such as WD-40 domains or leucine-rich
      repeats (LRRs). The kelch repeats of the family described here form a potential
      protein-protein interaction domain, as molecular modelling of the kelch repeats
      according to the galactose oxidase crystal structure (the only solved structure
      containing kelch repeats) predicts a beta-propeller. The identification of this
      family of F-box proteins greatly expands the field of plant F-box proteins and
      suggests that controlled degradation of cellular proteins via the ubiquitin
      pathway could play a critical role in multiple plant cellular processes.

PMID- 11516155
TI  - Sugar-responsible elements in the promoter of a gene for beta-amylase of sweet
      potato.
AB  - Expression of genes coding for sporamin and beta-amylase, the two most abundant
      proteins in storage roots of sweet potato, is coordinately inducible in atypical
      vegetative tissues by sugars. A sweet potato gene for beta-amylase (beta-Amy)
      with introns as well as a beta-Amy::GUS fusion gene composed of the beta-Amy
      promoter and the GUS coding sequence, both showed sugar-inducible expression in
      leaves of transgenic tobacco which occurred via a hexokinase-independent pathway.
      Analyses using various 5'-terminal and internal deletions of the beta-Amy
      promoter indicated that truncated promoters of beta-Amy containing a sequence
      between -901 and -820, relative to the transcription start site, and the basic
      promoter region can confer sugar-inducible expression. This 82 bp region
      contained the TGGACGG sequence that plays an essential role in the sugar
      inducible expression of the truncated promoter of the sporamin gene. Deletion or
      base substitutions of this element in the truncated beta-Amy promoter abolished
      the sugar-inducible expression, the results suggesting that the TGGACGG element
      plays an important role in the coordinate induction of expression of genes for
      beta-amylase and sporamin by sugars.

PMID- 11516154
TI  - A novel plastid-targeted J-domain protein in Arabidopsis thaliana.
AB  - Arabidopsis cDNAs encoding ATJ11, the smallest known J-domain protein, have been
      isolated and characterized. The precursor protein of 161 amino acid residues was
      synthesized in vitro and imported by isolated pea chloroplasts where it was
      localized to the stroma and cleaved to a mature protein of 125 amino acid
      residues. The mature protein consists of an 80 amino acid J-domain, and N- and C
      terminal extensions of 24 and 21 amino acid residues, respectively, which show no
      similarity to regions in other DnaJ-related proteins. ATJ11 produced in
      Escherichia coli stimulated the weak ATPase activity of E. coli DnaK, but was
      unable to stimulate refolding of firefly luciferase by DnaK, and inhibited
      refolding by DnaK, DnaJ and GrpE. ATJ11 is encoded by a single-copy gene on
      chromosome 4, and is expressed in all plant organs examined. A paralogue of
      ATJ11, showing 72% identity, is encoded in a 4.5 Mb duplication of chromosome 4
      on chromosome 2. These proteins represent a novel class of J-domain proteins.

PMID- 11516156
TI  - Impact of the third-strand orientation on the thermodynamic stability of the four
      way DNA junction.
AB  - The physical properties of a triple-helical DNA four-way junction J(T2T4) have
      been characterized by means of UV spectroscopy, CD spectroscopy, and differential
      scanning calorimetry (DSC). J(T2T4) is another four-way junction that was
      designed in addition to J(T1T3) (N. Makube and H. H. Klump (2000) Arch. Biochem.
      Biophys. 377, 31-42) to study the effects of third strands on the stability of
      the four-way junction with triple-helical arms. The pH titration curves
      illustrate the sequential folding of single strands to double-helical four-way
      junctions and finally the binding of third strands to their respective W-C
      duplexes. CD measurements confirm triplex formation under appropriate pH and
      ionic strength conditions. The CD spectra also suggest different melting patterns
      for the triple-helical arms of J(T2T4). The melting temperature as a function of
      pH or ionic strength characterizes the effect of the third strands on the
      structural stability. Increased sodium concentration and low pH conditions
      enhances and stabilizes the overall structure of the junction. The results also
      indicate that all triplexes in J(T2T4) are formed in the absence of salt and at
      low pH; however, the junction may, under these conditions, assume a conformation
      different from the one assumed in the presence of salt. Through the deconvolution
      of DSC data, the calorimetric enthalpies associated with melting of arms of the
      junctions were determined. The loops are designed to have the same enthalpic
      effect on the different arms. The stabilizing effect of the loops is more
      pronounced when those loops are shifted from arms 1 and 3 in J(T1T3) to arms 2
      and 4 in J(T2T4) without changing any of the sequences. Overall, J(T2T4) is
      slightly more stable than J(T1T3). The differences can be attributed to sequence
      effects rather than structural effects. All the results illustrate that binding
      of the third strand in either of the two orientations 5'5'3' (J(T2T4)) or 5'3'3'
      (J(T1T3)) stabilizes the underlying double-helical four-way junction and its
      triple-helical arms.

PMID- 11516157
TI  - Complex effects of molecular chaperones on the aggregation and refolding of
      fibroblast growth factor-1.
AB  - Fibroblast growth factor one (FGF-1) exists in a molten globule (MG)-like state
      under physiological conditions (neutral pH, 37 degrees C). It has been proposed
      that this form of the protein may be involved in its atypical membrane transport
      properties. Macromolecular chaperones have been shown to bind to MG states of
      proteins as well as to be involved in protein membrane transport. We have
      therefore examined the effect of such proteins on the aggregation and refolding
      of FGF-1 to evaluate whether they might play a role in FGF-1 transport. The
      proposed chaperone alpha-crystallin was found to strongly inhibit the aggregation
      of the MG state of FGF-1. Curiously, two other proteins of similar size and
      charge (thyroglobulin and a monoclonal IgM immunoglobulin) with no previously
      reported chaperone properties were also found to have a related effect. In
      contrast, the chaperone GroEL/ES induced further aggregation of MG-like FGF-1 but
      had no effect on the native conformation. Both chaperones stimulated refolding to
      the native state (25 degrees C) but had no detectable effect when FGF-1 was
      refolded to the MG state (37 degrees C). This suggests that disordered
      intermediates are present in the folding pathways of the native and MG-like FGF
      conformations which differ from the MG-like state induced under physiological
      conditions. FGF-1 does, therefore, interact with molecular chaperones, although
      this may involve both the MG and the native states of the protein.

PMID- 11516158
TI  - Homology model of dihydropyridine receptor: implications for L-type Ca(2+)
      channel modulation by agonists and antagonists.
AB  - L-type calcium channels (LCCs) are transmembrane (TM) proteins that respond to
      membrane depolarization by selectively permeating Ca(2+) ions. Dihydropyridine
      (DHP) agonists and antagonist modulate Ca(2+) permeation by stabilizing,
      respectively, the open and closed states of the channel. The mechanism of action
      of these drugs remains unclear. Using, as a template, the crystal structure of
      the KcsA K(+) channel (Doyle et al. (1998) Science 280, 69-77), we have built
      several homology models of LCC with alternative alignments of TM segments between
      the proteins. In each model, nifedipine was docked in the pore region and in the
      interface between repeats III and IV. Several starting structures were generated
      by constraining the ligand to residues whose mutations reportedly affect DHP
      binding (DHP-sensing residues). These structures were Monte Carlo-minimized with
      and without constraints. In the complex with the maximum number of contacts
      between the ligand and DHP-sensing residues and the lowest ligand-receptor
      energy, the drug fits snugly in the "water-lake" cavity between segments S6s,
      which were aligned with M2 segment of KcsA as proposed for Na(+) channel (Lipkind
      and Fozzard (2000) Biochemistry 39, 8161-8170). In the flattened-boat
      conformation of DHP ring, the NH group at the stern approaches the DHP-sensing
      tyrosines in segments IIIS6 and IVS6. Stacking interactions of IVS6 Tyr with the
      bowsprit aromatic ring stabilize the ligand's orientation in which the starboard
      COOMe group coordinates Ca(2+) ion chelated by two conserved glutamates in the
      selectivity filter. In the inverted teepee structure of LCC, the portside COOMe
      group approaches a bracelet of conserved hydrophobic residues at the helical
      bundle crossing, which may function as the activation gate. The dimensions of the
      gate may readily change upon small rotation of the pore-forming TM segments. The
      end of the portside group is hydrophobic in nifedipine, (R)-Bay K 8644, and other
      antagonists. Favorable interactions of this group with the hydrophobic bracelet
      would stabilize its closed conformation. In contrast, (S)-Bay K 8644 and several
      other agonists have hydrophilic groups at the portside. Unfavorable interactions
      of the hydrophilic group with the hydrophobic bracelet would destabilize its
      closed conformation thereby stabilizing the open conformation. In the agonist
      bound channel, Ca(2+) ions would permeate between the hydrophilic face of the
      ligand and conserved hydrophilic residues in segments IS6 and IIS6. Our model
      suggests mutational experiments that could further our understanding of the
      pharmacological modulation of voltage-gated ion channels.

PMID- 11516159
TI  - The role of serine hydroxymethyltransferase isozymes in one-carbon metabolism in
      MCF-7 cells as determined by (13)C NMR.
AB  - The role of cytosolic and mitochondrial serine hydroxymethyltransferase in
      supplying one-carbon groups for purine and thymidylate biosynthesis in MCF-7
      cells was investigated by observing folate-mediated one-carbon metabolism of l-[3
      (13)C]serine, [2-(13)C]glycine, and [(13)C]formate. (13)C NMR was used to follow
      the incorporation of label into carbons 2 and 8 of purines and the methyl group
      attached to carbon 5 of thymidylate. The percentage enrichment of the (13)C label
      in purines was determined from the splitting patterns of the (1)H NMR spectra of
      C2 and C8 of adenine and C8 of guanine. The results show that formate is the
      major precursor in the cytosol of the one-carbon group in 10
      formyltetrahydrofolate, which is used in purine biosynthesis, and the one-carbon
      group in 5,10-methylenetetrahydrofolate, which is used in thymidylate
      biosynthesis. Formate is formed in the mitochondria from carbon 3 of serine. The
      cleavage of serine to glycine and 5,10-methylenetetrahydrofolate by cytosolic
      serine hydroxymethyltransferase does not appear to be a major source of one
      carbon groups for either purine or thymidylate biosynthesis. Carbon 3 of serine
      accounts for about 95% of the one-carbon pool, suggesting that other sources of
      one-carbon groups represent only minor pathways. [2-(13)C]Glycine is not a donor
      of one-carbons groups, confirming that MCF-7 cells lack a functional glycine
      cleavage system.

PMID- 11516160
TI  - Temperature effects on the allosteric transition of ATP sulfurylase from
      Penicillium chrysogenum.
AB  - The effects of temperature on the initial velocity kinetics of allosteric ATP
      sulfurylase from Penicillium chrysogenum were measured. The experiments were
      prompted by the structural similarity between the C-terminal regulatory domain of
      fungal ATP sulfurylase and fungal APS kinase, a homodimer that undergoes a
      temperature-dependent, reversible dissociation of subunits over a narrow
      temperature range. Wild-type ATP sulfurylase yielded hyperbolic velocity curves
      between 18 and 30 degrees C. Increasing the assay temperature above 30 degrees C
      at a constant pH of 8.0 increased the cooperativity of the velocity curves. Hill
      coefficients (n(H)) up to 1.8 were observed at 42 degrees C. The bireactant
      kinetics at 42 degrees C were the same as those observed at 30 degrees C in the
      presence of PAPS, the allosteric inhibitor. In contrast, yeast ATP sulfurylase
      yielded hyperbolic plots at 42 degrees C. The P. chrysogenum mutant enzyme,
      C509S, which is intrinsically cooperative (n(H) = 1.8) at 30 degrees C, became
      more cooperative as the temperature was increased yielding n(H) values up to 2.9
      at 42 degrees C. As the temperature was decreased, the cooperativity of C509S
      decreased; n(H) was 1.0 at 18 degrees C. The cumulative results indicate that
      increasing the temperature increases the allosteric constant, L, i.e., promotes a
      shift in the base-level distribution of enzyme molecules from the high MgATP
      affinity R state toward the low MgATP affinity T state. As a result, the enzyme
      displays a true "temperature optimum" at subsaturating MgATP. The reversible
      temperature-dependent transitions of fungal ATP sulfurylase and APS kinase may
      play a role in energy conservation at high temperatures where the organism can
      survive but not grow optimally.

PMID- 11516161
TI  - Identification of a novel phosphorylation motif for CDPKs: phosphorylation of
      synthetic peptides lacking basic residues at P-3/P-4.
AB  - The Ca(2+)-dependent protein kinases (CDPKs) are members of a large subfamily of
      protein kinases in plants that have been implicated in the control of numerous
      aspects of plant growth and development. One known substrate of the CDPKs is the
      ER-located ACA2 calcium pump, which is regulated by phosphorylation of Ser(45).
      In the present study, a synthetic peptide based on the known regulatory
      phosphorylation site (RRFRFTANLS(45)KRYEA) was efficiently phosphorylated in
      vitro by CDPKs but not a plant SNF1-related protein kinase. Phosphorylation of
      the Ser(45)-ACA2 peptide was surprising because the sequence lacks basic residues
      at P-3/P-4 (relative to the phosphorylated Ser at position P) that are considered
      to be essential recognition elements for CDPKs. We demonstrate that
      phosphorylation of the Ser(45)-ACA2 peptide is dependent on the cluster of basic
      residues found N-terminal (P-6 to P-9) as well as C-terminal (P + 1/P + 2) to the
      phosphorylated Ser. The results establish a new general phosphorylation motif for
      CDPKs: [Basic-Basic-X-Basic]-phi-X(4)-S/T-X-Basic (where phi is a hydrophobic
      residue). The motif predicts a number of new phosphorylation sites in plant
      proteins. Evidence is presented that the novel motif may explain the
      phosphorylation by CDPKs of Ser271 in the aquaporin PM28A.

PMID- 11516162
TI  - Bulk production and functional analyses of mouse CD55's native and deglycosylated
      active domains.
AB  - We report the use of methylotrophic yeast Pichia pastoris as a host to
      efficiently express complement control protein repeats (CCPs) 1-4 of mouse decay
      accelerating factor (DAF, CD55) as a soluble protein. With this system, the mouse
      DAF CCP1-4-active-domain-containing module linked to a 6x His tag at its C
      terminus was secreted into the culture supernatant at 15 mg/L after 24 h of
      induction with methanol. A mouse DAF CCP1-4 mutant protein in which its two
      potential N-glycosylation sites were deleted by changing Asn(187) and Asn(262) to
      Gln was also produced. Using Ni(2+)-immobilized agarose affinity chromatography,
      the recombinant mouse DAF modules with their 6x His tags could be one-step
      isolated to SDS-PAGE purity. Polyclonal antibody against native mouse DAF CCP1-4
      was raised by immunizing NZW rabbits with the purified product. Measurements of
      the bioactivities of the wild-type and mutant mouse DAF proteins in C3b uptake
      assays showed no differences in regulatory activities in either the classical or
      the alternative pathways. With the use of the mutant DAF protein, small rod
      shaped crystals were produced and preliminary data obtained. The production of
      large quantities of functional recombinant mouse DAF CCP1-4 modules and their
      antibody offers the opportunity to study DAF structure and DAF function in vivo.

PMID- 11516163
TI  - Effect of three flavonoids, 5,7,3',4'-tetrahydroxy-3-methoxy flavone, luteolin,
      and quercetin, on the stimulus-induced superoxide generation and tyrosyl
      phosphorylation of proteins in human neutrophil.
AB  - The effect of three flavonoids, 5,7,3',4'-tetrahydoxy-3-methoxy flavone (THMF),
      luteolin, and quercetin, on the stimulus-induced superoxide generation and
      tyrosyl phosphorylation of proteins in human neutrophils were investigated. When
      the cells were preincubated with these flavonoids, the superoxide generation
      induced by N-formyl-methionyl-leucyl-phenylalanine (fMLP) was significantly
      suppressed, showing a dependence on amounts of the flavonoid. The suppressing
      effect of the flavonoid was THMF > luteolin > quercetin. These flavonoids also
      suppressed the superoxide generation induced by phorbol 12-myristate 13-acetate.
      In this case also, THMF was more effective than luteolin and quercetin. On the
      other hand, the superoxide generation induced by arachidonic acid was markedly
      suppressed by quercetin. The suppressing effect was quercetin >> THMF > luteolin.
      THMF, luteolin, and quercetin significantly suppressed tyrosyl phosphorylation of
      80.1-, 58.0-, and 45.0-kDa proteins in fMLP-treated human neutrophils. The
      suppression depended on the concentration of the flavonoids, and the inhibition
      of tyrosyl phosphorylation was in parallel to that of the fMLP-induced superoxide
      generation, respectively. While luteolin and quercetin showed a weak hemolytic
      activity at 2.5 mM, THMF showed almost no hemolytic activity even at 5 mM,
      suggesting an advantage of THMF for its clinical use.

PMID- 11516164
TI  - Induction of rabbit lung CYP4A4 prostaglandin omega-hydroxylase by various
      steroid hormones.
AB  - Cytochrome P4504A4 (CYP4A4) is expressed at low basal levels in adult rabbit
      lungs, but is significantly induced during pregnancy by an unknown mechanism. As
      the gradual rise in CYP4A4 levels appears to coincide with the progressive
      increase in several steroid hormones throughout pregnancy, we examined the
      induction of CYP4A4 after treatment with various steroid hormones by monitoring
      both the CYP4A4 mRNA level and the CYP4A4-specific prostaglandin E(1) (PGE(1))
      omega-hydroxylation reaction in rabbit lung microsomes. Treatment with
      progesterone and/or a synthetic glucocorticoid (dexamethasone) resulted in a
      significant increase in PGE(1) omega-hydroxylase activity, whereas estradiol,
      aldosterone, dehydroepiandrosterone, and dehydroepiandrosterone sulfate did not.
      These studies indicated that dexamethasone was a more potent inducer of CYP4A4
      than progesterone. Simultaneous injection of dexamethasone and
      glucocorticoid/progesterone antagonists (RU38486, RU40555, or RU43044) inhibited
      the increase in PGE(1) omega-hydroxylase activity as well as mRNA levels by
      approximately 50%. In addition, simultaneous treatment with both dexamethasone
      and progesterone did not result in an additive or synergistic effect on PGE(1)
      omega-hydroxylase activity. These data indicate that, while distinctive receptors
      for glucocorticoid and/or progesterone are involved, induction may also require
      common or interacting regulatory elements (yet to be determined) in the CYP4A4
      gene. These findings implicate both of these steroid receptors (PR/GR) in the
      induction of CYP4A4 in rabbit lung.

PMID- 11516165
TI  - Mitochondrial electron transport inhibitors cause lipid peroxidation-dependent
      and -independent cell death: protective role of antioxidants.
AB  - Mitochondrial electron transport inhibitors induced two distinct pathways for
      acute cell death: lipid peroxidation-dependent and -independent in isolated rat
      hepatocytes. The toxic effects of mitochondrial complex I and II inhibitors,
      rotenone (ROT) and thenoyltrifluoroacetone (TTFA), respectively, were dependent
      on oxidative stress and lipid peroxidation, while cell death induced by
      inhibitors of complexes III and IV, antimycin A (AA) and cyanide (CN),
      respectively, was caused by MMP collapse and loss of cellular ATP. Accordingly,
      cellular and mitochondrial antioxidant depletion or supplementation, in general,
      resulted in a dramatic potentiation or prevention, respectively, of toxic injury
      induced by complex I and II inhibitors, with little or no effect on complex III
      and IV inhibitor-induced toxicity. ROT-induced oxidative stress was prevented by
      the addition of d-alpha-tocopheryl succinate (TS) but surprisingly TS did not
      afford hepatocytes protection against TTFA-induced oxidative damage. TS treatment
      prevented ROT-induced mitochondrial lipid hydroperoxide formation but had no
      effect on the loss of mitochondrial GSH or cellular ATP, suggesting a
      mitochondrial lipid peroxidation-mediated mechanism for ROT-induced acute cell
      death. In contrast, only fructose treatment provided excellent cytoprotection
      against AA- and CN-induced toxicity. Our findings indicate that complex III and
      IV inhibitors cause a rapid and severe depletion of cellular ATP content
      resulting in acute cell death that is dependent on cellular energy impairment but
      not lipid peroxidation. In contrast, inhibitors of mitochondrial complex I or II
      moderately deplete cellular ATP levels and thus cause acute cell death via a
      lipid peroxidation pathway.

PMID- 11516166
TI  - Serine 331 is the major site of receptor phosphorylation induced by agents that
      activate protein kinase G in HEK 293 cells overexpressing thromboxane receptor
      alpha.
AB  - Human embryonic kidney (HEK)293 cells stably transfected with the His-tagged
      thromboxane receptor alpha (TPalpha) was used to study the phosphorylation and
      desensitization of the receptor induced by 8-bromo-cyclic GMP (8-Br-cGMP), sodium
      nitroprusside (SNP), or S-nitroso-glutathione (SNG). These agents are known to
      activate cGMP-dependent protein kinase (PKG). Pretreatment of cells with these
      agents attenuated significantly agonist I-BOP induced Ca(2+) release. These
      agents also induced dose-dependent phosphorylation of the TPalpha as demonstrated
      by increased (32)P-labeling of the receptor from cells prelabeled with (32)Pi. To
      facilitate the identification of the intracellular domains involved in
      phosphorylation, glutathione S-transferase (GST)-intracellular domain fusion
      proteins were used as substrates for the purified PKG. It was found that only the
      GST-C-terminal tail fusion protein could serve as a substrate for the PKG. To
      identify the specific serine/threonine residues in the C-terminal tail being
      phosphorylated, various alanine mutants of these serine/threonine residues were
      checked for their ability to serve as substrates. It was found that the Ser-331
      of the C-terminal tail was primarily involved in the PKG-mediated
      phosphorylation. That Ser-331 is a predominant site of phosphorylation was
      supported by in vivo studies in which HEK293 cells expressing the S331A mutant
      receptor showed little phosphorylation induced by any of the above three agents.
      Furthermore, HEK293 cells expressing the S331A mutant receptor pretreated with
      any of the above three agents became responsive to the agonist I-BOP-induced
      Ca(2+) release. These results indicate that Ser-331 of the TPalpha is the primary
      site responsible for the phosphorylation and the desensitization of the receptor
      induced by agents that activate the PKG.

PMID- 11516167
TI  - Ubiquitin-dependent 26S proteasomal pathway: a role in the degradation of native
      human liver CYP3A4 expressed in Saccharomyces cerevisiae?
AB  - Cytochrome P450, CYP3A4, is the dominant human liver endoplasmic reticulum (ER)
      hemoprotein enzyme, responsible for the metabolism of over 60% of clinically
      relevant drugs. We have previously shown that mechanism-based suicide
      inactivation of CYP3A4 and its rat liver ER orthologs, CYPs 3A, via heme
      modification of their protein moieties, results in their ubiquitin (Ub)-dependent
      26S proteasomal degradation (Korsmeyer et al. (1999) Arch. Biochem. Biophys. 365,
      31; Wang et al. (1999) Arch. Biochem. Biophys. 365, 45). This is not surprising
      given that the heme-modified CYP3A proteins are structurally damaged. To
      determine whether the turnover of the native enzyme similarly recruited this
      pathway, we heterologously expressed this protein in wild-type Saccharomyces
      cerevisiae and mutant strains (hrd1Delta, hrd2-1, and hrd3Delta) previously shown
      to be deficient in the Ub-dependent 26S proteasomal degradation of the polytopic
      ER protein 3-hydroxy-3-methylglutaryl-CoA reductase (isoform Hmg2p), the rate
      limiting enzyme in sterol biosynthesis, as well as in strains deficient in ER
      associated Ub-conjugating enzymes, Ubc6p and/or Ubc7p (Hampton et al. (1996) Mol.
      Biol. Cell 7, 2029; Hampton and Bhakta (1997) Proc. Natl. Acad. Sci. USA 94,
      12,944). Our findings reveal that in common with the degradation of Hmg2p, that
      of native CYP3A4 also requires Hrd2p (a subunit of the 19S cap complex of the 26S
      proteasome) and Ubc7p, and to a much lesser extent Hrd3p, a component of the ER
      associated Ub-ligase complex. In contrast to Hmg2p-degradation, that of native
      CYP3A4 does not appear to absolutely require Hrd1p, another component of the ER
      associated Ub-ligase complex. Furthermore, studies in a S. cerevisiae pep4Delta
      strain proven to be deficient in the vacuolar degradation of carboxypeptidase Y
      indicated that CYP3A4 degradation is also largely independent of vacuolar
      (lysosomal) proteolytic function. The degradation of two other native ER
      proteins, Sec61p and Sec63p, normal components of the ER translocon, were also
      examined in parallel and found to be stabilized to some extent in HRD2- and UBC7
      deficient strains. Together these findings attest to the remarkable mechanistic
      diversity in the normal degradation of ER proteins.

PMID- 11516168
TI  - Discriminant responses of the catalytic unit and glucose 6-phosphate transporter
      components of the hepatic glucose-6-phosphatase system in Ehrlich ascites-tumor
      bearing mice.
AB  - The effect of Ehrlich ascites tumor cells, in vivo, on the hepatic glucose-6
      phosphatase (G6Pase) system was examined. The V(max) for glucose 6-phosphate
      hydrolysis by G6Pase was reduced by 40% and a greater than 15-fold decrease in
      mRNA encoding the catalytic unit of the G6Pase system was observed 8 days after
      injection with tumor cells. Blood glucose concentration was decreased from 169 +/
      17 to 105 +/- 9 mg/dl in tumor-bearing mice. There was no change in the G6P
      transporter (G6PT) mRNA level. However, there was a significant decrease in G6P
      accumulation into hepatic microsomal vesicles derived from tumor-bearing mice.
      Decreased G6P accumulation was also associated with a decrease in G6Pase
      hydrolytic activity in the presence of vanadate, a potent catalytic-unit
      inhibitor. In addition, G6P accumulation was nearly abolished in microsomes
      treated with N-bromoacetylethanolamine phosphate, an irreversible inhibitor of
      the G6PT. These results demonstrate that the catalytic unit and G6PT components
      of the G6Pase system can be discriminantly regulated, and that microsomal glucose
      6-phosphate uptake is dependent on catalytic unit activity as well as G6PT
      action.

PMID- 11516169
TI  - Inhibition of adenylylcyclase activity in mouse cerebellum membranes upon
      hydrolysis of triacylglycerols by triacylglycerol lipase, but not phospholipids
      by phospholipase A(2).
AB  - We previously showed that arachidonic acid and related unsaturated free fatty
      acids (U-FFAs) inhibit the activity of adenylylcyclase in brain membranes of
      mice. The level of U-FFAs elevates when the hydrolysis of triacylglycerols (TAGs)
      and phospholipids is promoted. In this study, we examined whether activation of
      triacylglycerol lipase (TAG lipase) and phospholipase A(2) (PLA(2)) results in
      the inhibition of adenylylcyclase activity in cerebellum membranes of mice.
      Incubation of Intralipos with TAG lipase in the presence of membranes mainly
      released oleic acid and linoleic acid and caused > or =95% inhibition of
      adenylylcyclase activity. In contrast, PLA(2), though releasing substantial
      amounts of U-FFAs, increased the enzymatic activity. To account for this
      difference, we examined how by-products formed in U-FFA release by TAG lipase and
      PLA(2) operated on the arachidonic acid-induced inhibition.
      Lysophosphatidylcholne and some other lysophospholipids, produced by PLA(2),
      enhanced the adenylylcyclase activity and attenuated the inhibitory effect of
      arachidonic acid. On the other hand, no such effects were found with by-products
      of TAG lipase-mediated lipolysis. Rather, monoacylglycerols having U-FFAs,
      possibly formed by TAG lipase, potentiated the arachidonic acid-induced
      inhibition of adenylylcyclase. Bovine serum albumin, added into the mixture for
      the pretreatment of membranes with TAG lipase, prevented the inhibition of
      adenylylcyclase. These results indicate that by-products formed in U-FFA release
      have a crucial role for the U-FFA's action on adenylylcyclase and that U-FFAs
      released from TAG are an inhibitor of adenylylcyclase. It may be that albumin in
      plasma, and thus FFA-binding proteins within cells, are of importance in
      protecting adenylylcyclase upon U-FFA release.

PMID- 11516170
TI  - Characterization of parazoanthoxanthin A binding to a series of natural and
      synthetic host DNA duplexes.
AB  - Parazoanthoxanthin A is a fluorescent yellow nitrogenous pigment of the group of
      zoanthoxanthins, which show a broad range of biological activity. These include,
      among others, the ability to bind to DNA. In this study we have used a variety of
      spectroscopic (intrinsic fluorescence emission and UV-spectroscopy) and
      hydrodynamic techniques (viscometry) to characterize in more detail the binding
      of parazoanthoxanthin A to a variety of natural and synthetic DNA duplexes in
      different buffer conditions. Our results reveal the following five significant
      features: (i) Parazoanthoxanthin A exhibits two modes of DNA binding: One binding
      mode exhibits properties of intercalation, while the second binding mode is
      predominantly electrostatic in origin. (ii) The apparent binding "site size" for
      parazoanthoxanthin A near physiological salt concentration (100 mM NaCl) is in
      the range of 7 +/- 1 base pairs for natural genomic DNA duplexes (calf thymus and
      salmon testes DNA) and alternating synthetic polynucleotides (poly[d(AT)].
      poly[d(AT)] and poly[d(GC)]. poly[d(GC)]). A slightly larger apparent binding
      site size of 9 +/- 1 bp was obtained for parazoanthoxanthin A binding to the
      synthetic homopolymer poly[d(A)]. poly[d(T)]. (iii) Near physiological salt
      concentration (100 mM NaCl) parazoanthoxanthin A binds with the same approximate
      binding affinity of 2-5 x 10(5) M(-1) to all DNA polymers studied. (iv) At low
      salt concentration, parazoanthoxanthin A preferentially binds alternating
      poly[d(AT)]. poly[d(AT)] and poly[d(GC)]. poly[d(GC)] host duplexes. (v)
      Parazoanthoxanthin A inhibits DNA polymerase in vitro.

PMID- 11516171
TI  - N-terminal deletions and His-tag fusions dramatically affect expression of
      cytochrome p450 2C2 in bacteria.
AB  - The expression of mutants with deletions in the N-terminal signal-anchor sequence
      of cytochrome P450 2C2 and His-tag fusions was examined in Escherichia coli to
      determine the influence of N-terminal sequences on expression of the protein. Two
      mutants predicted to be translocated across the membrane inhibited bacterial
      growth. In other mutants, deletion of the N-terminal transmembrane domain
      (residues 2-20) reduced expression of functional P450 by about 75% and further
      deletion of the following linker sequence (residues 21-27) resulted in a modest
      further decrease. Expression of the mutant with residues 2-27 deleted contrasts
      with the lack of expression of functional protein if only the linker was deleted,
      which suggests that the linker sequence is critical for expression only if the
      protein is inserted into the membrane by the transmembrane domain. Fusion
      proteins of green fluorescent protein with full-length P450 2C2 and 2C2(Delta2
      20) were predominantly membrane-associated in vivo as determined by fluorescence
      microscopy. Subcellular fractionation of bacteria expressing these proteins and
      extraction of the proteins from the membrane by high salt or alkaline buffer
      demonstrated that P450 2C2 was an integral membrane protein while 2C2(Delta2-20)
      was a peripheral membrane protein that associated with the membrane mainly by
      hydrophobic interactions. Residues 1-27 of P450 2C2 fused to green fluorescent
      protein resulted in a redistribution of fluorescence from cytosol to membrane,
      which, with the deletion studies, indicates that the P450 signal-anchor is both
      necessary and sufficient for normal membrane targeting and is the sole
      transmembrane domain of cytochrome P450 2C2 in bacteria. Addition of a His-tag at
      the N-terminus completely restored wild-type expression levels to the 2C2(Delta2
      20) mutants in bacteria. In insect cells, functional 2C2(Delta2-20) was not
      expressed but an N-terminal His-tag also restored full expression. The increase
      in expression may be related to decreased association with the membrane mediated
      by the His-tag.

PMID- 11516172
TI  - Transient expression of CYP1A1 in rat epithelial cells cultured in suspension.
AB  - Suspension of human epidermal cells in methylcellulose-containing medium induces
      CYP1A1 by a mechanism requiring functional Ah receptor (AhR). In present work
      CYP1A1 mRNA was induced in a variety of cultured rat epithelial cells by
      suspension, but the induction was transient, with CYP1A1 mRNA reaching maximal
      levels by 5 h and disappearing by 12 h. Though the methylcellulose itself
      contained no detectable ligand, (a) suspension activated the AhR, as judged by
      mobility shift assays, (b) the AhR competitive inhibitor alpha-naphthoflavone
      inhibited suspension-mediated induction, and (c) induction was dependent upon
      dioxin responsive transcriptional elements in the CYP1A1 promoter. The rapid
      disappearance of CYP1A1 mRNA after 5 h of suspension was unaffected by the
      addition of TCDD but was prevented by the inclusion of the protein synthesis
      inhibitor cycloheximide. Thus the downregulation appears to be mediated by a
      novel short-lived protein induced or activated by suspension.

PMID- 11516173
TI  - Characterization of a secretase activity for placental leucine aminopeptidase.
AB  - Placental leucine aminopeptidase (P-LAP) is believed to play an important role in
      the inactivation of small regulatory peptides. P-LAP exists in both membrane
      bound and soluble forms and cDNA cloning has demonstrated that P-LAP is a type II
      membrane protein, which means that its soluble form is released by a specific
      proteolytic cleavage. In this report, we studied this process in COS7 cells.
      Inhibitors of serine or aspartic proteases did not affect the secretion of P-LAP,
      while EDTA and 1,10-phenanthroline inhibited it. In addition, we transfected P
      LAP expression vectors that have point mutations of the cleavage site or deletion
      of the juxtamembrane stalk. Point mutations of the cleavage site resulted in
      significantly lower secretion of P-LAP. On the contrary, the distance to cleavage
      site showed no relation to P-LAP secretion. These results suggest that P-LAP
      secretase has a metalloprotease activity which depends on the amino acid sequence
      of the cleavage site.

PMID- 11516174
TI  - Lower copper, zinc-superoxide dismutase protein but not mRNA in organs of copper
      deficient rats.
AB  - Copper deficiency was induced in Sprague Dawley rats by dietary restriction to
      confirm and extend studies on copper, zinc-superoxide dismutase (Cu,Zn-SOD). Male
      rats restricted from copper in two models, a traditional postweanling model
      examining 50-day-old rats fed a low copper diet for 32 days (postnatal) and a
      gestational-lactational model examining 23-day-old male offspring of dams started
      on copper deficiency at day 7 of gestation (perinatal), showed signs of severe
      copper deficiency including anemia, and cardiac hypertrophy. Compared to control
      rats, copper-deficient rats exhibited lower copper concentrations in the liver,
      heart, brain, and kidney and lower Cu,Zn-SOD activity in the same organs with the
      exception of the brain in the postnatal model. In addition, there was a
      significant reduction in Cu,Zn-SOD protein detected by Western immunoblot
      proportional (r = 0.96) to the reduction in Cu,Zn-SOD activity. In the liver the
      reduction in Cu,Zn-SOD protein was approximately 50%. The reduction in Cu,Zn-SOD
      protein is likely due to a post-transcriptional mechanism as steady-state Cu,Zn
      SOD mRNA levels measured by Northern hybridization were not altered by copper
      deficiency in any organ studied (liver, heart, and brain). Perhaps apo-Cu,Zn-SOD
      is degraded faster than fully metal-loaded enzyme. The loss of Cu,Zn-SOD activity
      and protein reduces the antioxidant defense capacity of copper-deficient organs.

PMID- 11516175
TI  - Purification and antigenicity of flavone synthase I from irradiated parsley
      cells.
AB  - Flavone synthase I, a soluble 2-oxoglutarate-dependent dioxygenase catalyzing the
      oxidation of flavanones to flavones in several Apiaceae species, was induced in
      parsley cell cultures by continuous irradiation with ultraviolet/blue light for
      20 h. The enzyme was extracted from these cells and purified by a revised
      purification protocol including the fractionation on hydroxyapatite, Fractogel
      EMD DEAE, and Mono Q anion exchangers, which resulted in an apparently
      homogeneous flavone synthase at approximately 10-fold higher yield as compared to
      the previous report. The homogeneous enzyme was employed to raise an antiserum in
      rabbit for partial immunological characterization. The specificity of the
      polyclonal antibodies was demonstrated by immunotitration and Western blotting of
      the crude ammonium sulfate-fractionated enzyme as well as of the enzyme at
      various stages of the purification. High titer cross-reactivity was observed
      toward flavone synthase I, showing two bands in the crude extract corresponding
      to molecular weights of 44 and 41 kDa, respectively, while only the 41 kDa was
      detected on further purification. The polyclonal antiserum did not cross-react
      with recombinantly expressed flavanone 3beta-hydroxylase from Petunia hybrida or
      flavonol synthase from Citrus unshiu, two related 2-oxoglutarate-dependent
      dioxygenases involved in the flavonoid pathway.

PMID- 11516176
TI  - Immunohistochemical detection of betaine-homocysteine S-methyltransferase in
      human, pig, and rat liver and kidney.
AB  - Betaine-homocysteine S-methyltransferase (BHMT) has been shown to be expressed at
      high levels in the livers of all vertebrate species tested. It has also been
      shown to be abundant in primate and pig kidney but notably very low in rat kidney
      and essentially absent from the other major organs of monogastric animals. We
      recently showed by enzyme activity and Western analysis that pig kidney BHMT was
      only expressed in the cortex and was absent from the medulla. Using
      immunohistochemical detection, we report here that in human, pig, and rat kidney,
      BHMT is expressed in the proximal tubules of the cortex. Immunohistochemical
      staining for BHMT in human, pig, and rat liver indicate high expression in
      hepatocytes. The staining patterns are consistent with cytosolic expression in
      both organs.

PMID- 11516177
TI  - Intravascular device-related infections: antimicrobial catheters as a strategy
      for prevention.

PMID- 11516178
TI  - Infection prevention in necrotizing pancreatitis: an old challenge with new
      perspectives.
AB  - Necrotizing pancreatitis still remains a life-threatening disease despite several
      improvements in diagnosis, prevention and treatment. In recent years, some
      important questions have been answered such as the need for early intensive
      medical treatment rather than early surgery, but others are still strongly
      debated. The aim of this paper is to present an up-to-date assessment of current
      challenges in the management of necrotizing pancreatitis in order to prevent
      infection.

PMID- 11516179
TI  - The organization of infection control in Germany.
AB  - The authors outline the organization of infection control in Germany, focusing on
      official regulations, the training of infection control staff, and functions of
      the infection control committee and the availability of guidelines.

PMID- 11516180
TI  - Post-operative endophthalmitis: the application of hazard analysis critical
      control points (HACCP) to an infection control problem.
AB  - Hazard analysis critical control points (HACCP) is a quality assurance system
      widely used in the food industry to ensure safety. We adopted the HACCP approach
      when conventional infection control measures had failed to solve an ongoing
      problem with an increased incidence of postoperative endophthalmitis, and our
      ophthalmology unit was threatened with permanent cessation of intraocular
      surgery. Although time-consuming, the result was an entirely new set of protocols
      for the care of patients undergoing intraocular surgery, the development of an
      integrated care pathway, and a comprehensive and robust audit programme, which
      enabled intraocular surgery to continue in a new spirit of confidence. HACCP
      methodology has so far been little used in healthcare, but it might be usefully
      applied to a variety of apparently intractable infection control problems.

PMID- 11516181
TI  - A statistical approach to an outbreak of endophthalmitis following cataract
      surgery at a hospital in the West of Scotland.
AB  - The number of cases of endophthalmitis following cataract surgery caused
      considerable concern in a West of Scotland hospital throughout 1998 and early
      1999. A multi-disciplinary team including infection control nurses, doctors,
      public health officials,epidemiologists and statisticians was set up to
      investigate the situation. This paper examines the statistical issues surrounding
      the investigation. A method based on the Poisson distribution showed that the
      number of cases was significantly higher than expected. Fisher's Exact Test and
      Logistic Regression were then applied to the data from two related case control
      studies. These analyses showed that a higher risk of endophthalmitis was
      associated with being female, having a vitrectomy or having a previous history of
      respiratory disease. Finally, a method was devised to enable staff to recognize
      more quickly when the number of cases of endophthalmitis was becoming higher than
      expected. The method should find application in other clinical situations where
      the probability of rare events is known.

PMID- 11516182
TI  - Molecular epidemiological study on transmission of tuberculosis in a hospital for
      mentally handicapped patients in Havana, Cuba.
AB  - The IS 6110 restriction fragment length polymorphism (RFLP) analysis of
      Mycobacterium tuberculosis isolates has revolutionized the description of the
      epidemiology of tuberculosis. This technique has been used to confirm suspected
      cases of transmission in several institutional settings. In this study, we
      analysed by conventional and molecular epidemiological methods the unexpectedly
      high number of tuberculosis cases which occurred among 14 mentally handicapped
      patients and a healthcare worker in Havana's Psychiatric Hospital in the period
      from 1995 to 1998. Twelve M. tuberculosis isolates of the respective patients
      showed the same DNA fingerprint, consisting of nine bands. Three other different
      IS 6110 RFLP patterns with 10, eight, and 10 bands were observed. The results of
      RFLP analysis and of an additional epidemiological investigation allowed the
      identification of the probable source of this chain of transmission in the
      healthcare facility. This would not have been possible without the aid of DNA
      fingerprinting. Delays in diagnosis of the source patient and of the secondary
      cases, a tardy and deficient tuberculin skin test and the difficulties of
      management of mentally handicapped patients probably contributed to spread the M.
      tuberculosis strain in Havana's Psychiatric Hospital.

PMID- 11516183
TI  - Pre-sterilization bioburden in Scotland.

PMID- 11516184
TI  - Rate of transmission and endogenous origin of Candida albicans and Candida
      glabrata on adult intensive care units studied by pulsed field gel
      electrophoresis.
AB  - We determined the relative roles of endogenous origin and patient-to-patient
      transmission in Candida colonization of patients on adult intensive care units
      (ICU). A total of 48 Candida albicans and 18 Candida glabrata strains from
      various clinical samples of 28 long-term patients, hospitalized in two
      neurological ICUs between April and June 1999, were typed using pulsed field gel
      electrophoresis (PFGE). Three patients were co-colonized by both C. albicans and
      C. glabrata strains. Twenty-four C. albicans and 17 C. glabrata karyotypes were
      defined. The colonization was found to be polyclonal in six C. albicans and five
      C. glabrata patients. Twenty-six patients (93%) carried strains, which were not
      detected in other patients hospitalized at the same time, i.e. they were
      colonized by unique C. albicans and C. glabrata strains. Only two patients, who
      were hospitalized during the same period of time, although in different rooms of
      the same ICU, shared strains with an identical PFGE type, indicating possible
      patient-to-patient transmission. Patient-to-patient transmission of yeasts played
      a minor role on these ICUs.

PMID- 11516185
TI  - Production of antimicrobial substances, by hospital bacteria, active against
      other micro-organisms.
AB  - Fifty-nine clinical strains of bacteria, isolated from patients in the Regional
      Hospital of Talca, were studied. Seventy-four percent of these strains produced
      antibacterial substances, in comparison with 18% of the same bacterial species
      obtained from patients from a non-hospital habitat. Almost all the bacteria
      isolated from hospitalized patients demonstrated in vitro resistance to different
      antimicrobial agents. Pseudomonas aeruginosa was the most frequent species
      producing antibacterial substances and its products were of high potency, with a
      wide spectrum of antimicrobial activity. Cure of plasmid DNA, in most of the
      antibacterial-producer strains, resulted in the loss of their lethal activity and
      they also became susceptible in vitro to anti-microbials. These results indicated
      that such properties are encoded in extrachromosomal DNA. We believe that the
      knowledge of the antimicrobial activity and resistance to antimicrobials of
      bacteria from a hospital habitat can help explain the selection and persistence
      of such strains in this particular ecological niche.

PMID- 11516186
TI  - A district general hospital's method of post-operative infection surveillance
      including post-discharge follow-up, developed over a five-year period.
AB  - We report on a post-operative infection surveillance system which includes post
      discharge follow-up, developed over five years in a district general hospital in
      the West Midlands, UK. The methods used for following up 667 patients undergoing
      one of five representative surgical procedures are described. Emergency, elective
      and day-case procedures are included. A combination of healthcare worker
      questionnaire, telephone calls and patient questionnaire gave a follow-up rate of
      92.7%. The system took infection control staff an average of 40 min per patient
      (30 min inpatient assessment, 10 min post-discharge). Almost half (48%) of
      surgical site infections were diagnosed after discharge from hospital. The system
      worked equally well when conducted as part of the UK Nosocomial Infection
      National Surveillance Scheme (NINSS), or as in-house projects. It is likely that
      the system could be used in other areas with similar population characteristics
      and support from local general practitioners working in the community.

PMID- 11516187
TI  - High-level handwashing compliance in a community teaching hospital: a challenge
      that can be met!
AB  - Handwashing is the most important and least expensive measure for preventing the
      transmission of hospital-acquired infection. Compliance, however, rarely exceeds
      40%, even in intensive care units. The present study evaluated the effectiveness
      of the authors' infection control programme in relation to handwashing compliance
      of healthcare workers. Ten nursing students observed 300 uninformed staff members
      and recorded their handwashing practices throughout the working day. The
      observations were categorized by profession, gender, age, hospital unit and type
      of delivered care. In 1035 opportunities that required handwashing, the overall
      compliance was 76%. Healthcare workers washed hands before (68%) and after
      patient care (80%). Females complied more than males (69 vs. 80%, P<0.0001) and
      nurses more than physicians (81 vs. 69%, P<0.001). In intensive care units,
      overall compliance exceeded 97%, while in other wards and in the emergency
      departments, it approximated 61%. More handwashing was observed during the
      evening shift compared with the morning shift (P=0.02). Despite the high
      compliance, only 30% washed their hands for the required 10-20s. In conclusion,
      compliance with handwashing in the authors' institution is the highest reported
      to date, and reflects the intensive and incessant educational infection control
      programme.

PMID- 11516188
TI  - Poor hospital infection control practice in venepuncture and use of tourniquets.
AB  - Previous studies have indicated that tourniquets may act as reservoirs of
      pathogenic organisms and could therefore pose a risk to patients through cross
      infection. In this study, 200 tourniquets were sampled from health professionals
      working in a large teaching hospital. A parallel survey of control of infection
      was also undertaken. Staphylococcus aureus was isolated from 10 (5%) of the
      tourniquets sampled. Methicillin-resistant S. aureus was not isolated. Seventy
      five (37.5%) of the tourniquets sampled had visible blood stains; house officers
      (72.7%) and laboratory phlebotomists (69.2%) had the highest proportion of blood
      stained tourniquets. Tourniquets were owned on average for 1.86 years, with most
      respondents only obtaining a new tourniquet when the old tourniquet was lost.
      Three percent of respondents used a separate tourniquet for patients with known
      infective risk factors, e.g. HIV, MRSA. Twenty-seven percent of respondents did
      not wear gloves for venepuncture or did so only occasionally. Only 42% washed
      their hands both before and after venepuncture. Our survey reveals poor infection
      control practice, but a relatively low frequency of S. aureus contamination of
      tourniquets.

PMID- 11516189
TI  - Pulsed field gel electrophoresis typing of coagulase-negative staphylococci with
      decreased susceptibility to teicoplanin isolated from an intensive care unit.
AB  - Increased isolation of coagulase-negative staphylococci (CoNS) with decreased
      susceptibility to teicoplanin prompted this epidemiological survey in the authors
      intensive care unit. Of 224 medical and surgical patients with hepatobiliary
      disease, in hospital between December 1998 and July 1999, 14 (6.3%) had at least
      one isolate of CoNS with decreased susceptibility to teicoplanin. A total of 27
      isolates with decreased susceptibility to teicoplanin were recovered from these
      14 patients. Pulsed field electrophoresis (PFGE) with Sma I endonuclease
      demonstrated that CoNS isolates obtained from different patients were unrelated.
      In addition, different isolates obtain from the same patient were also unrelated,
      with the exception of two patients. Eighteen out of 27 isolates (66.7%) with
      decreased susceptibility to teicoplanin were recovered after an earlier treatment
      with teicoplanin or vancomycin (median 13.1 g, range 2.4-32.7 g per patient).
      Only four CoNS strains with decreased susceptibility to teicoplanin induced
      serious infection, all of which responded well to vancomycin therapy. Emergence
      of CoNS strains with decreased susceptibility to teicoplanin remained limited in
      hospitalized patients, and was not related to a clonal spread of a particular
      resistant strain.

PMID- 11516190
TI  - Surveillance of hospital-acquired infection in the Republic of Ireland: past,
      present and future.
AB  - There is increasing interest in the surveillance of hospital-acquired infection
      (HAI) in the Republic of Ireland due to a greater awareness of the consequences
      of antibiotic resistance, and consumer pressure in the form of public
      expectations of the quality of health care. To date there have been no nationwide
      prospective surveillance projects but surveillance has taken place in the form of
      participation in international and national studies, and the description of local
      outbreaks. Infection control teams and others have participated in projects such
      as a European study of HAI in intensive care units conducted in 1992, the second
      national prevalence study conducted in the UK in 1993 and two surveys of
      methicillin-resistant Staphylococcus aureus (MRSA) carried out in 1995 and 1999,
      the latter involving colleagues in Northern Ireland. There have been a number of
      local surveys of antibiotic-resistant bacteria including the molecular
      characterization of MRSA in Dublin hospitals, vancomycin-resistant enterococci,
      and Gram-negative bacteria such as Enterobacter spp. and Serratia spp. affecting
      compromised patients such as bone marrow transplant recipients. In the future, it
      is hoped to standardize case definitions, automate data entry, increase
      collaboration with surveillance initiatives in Northern Ireland and link in with
      European networks such as EARSS and HELICS. Apart from the need to improve the
      quality of health care in Irish hospitals, approximate costings suggest that
      there are potential savings of 7.5 pounds sterling -15 pounds sterling m to be
      made following a reduction of HAI rates of 15%.

PMID- 11516191
TI  - A one-day prevalence survey of hospital-acquired infections in Lebanon.
AB  - A one-day survey was carried out in 14 acute care hospitals in Lebanon in May
      1997, to determine the prevalence of nosocomial infection (NI) by site of
      infection, hospital department, micro-organism and pathology. Hospitals (N=14)
      with more than 50 beds were selected at random from the official Lebanese Health
      Ministry Registration Directory. All patients who presented that day on the ward
      and were not admitted or discharged, were included. Demographic, clinical and
      bacteriological data were recorded by two investigators, from medical chart
      review and by physical examinations performed by a trained physician. The overall
      prevalence of NI was 6.8% (95% CI: 5.1-8.4). Of 834 patients, the most frequent
      site of NI was the respiratory tract (30% of NI), followed by surgical site wound
      infection (28%) and urinary tract infection (18%). Pseudomonas sp. was the
      predominant pathogen, being isolated from 15 out of 71 episodes of NI. By
      logistic regression analysis, each additional day of hospital stay multiplied the
      risk of NI by 5%. Significant risk factors for NI included central i.v. catheter,
      adjusted odds ratio (OR 5.95, 95% CI: 2.27-15.49) and urinary catheter (OR 2.86,
      95% CI: 1.50-5.65). The presence of immunocompromising conditions also increased
      the risk of NI.

PMID- 11516192
TI  - Is the incidence of MRSA bacteraemia representative of the rate of MRSA infection
      in general?

PMID- 11516193
TI  - Rational protocols for testing faeces in the investigation of sporadic hospital
      acquired diarrhoea.

PMID- 11516194
TI  - Are contaminated flush solutions an overlooked source for catheter-related
      sepsis?

PMID- 11516195
TI  - Endoscope washers--a protocol for their use.

PMID- 11516196
TI  - Infections in long-term care institutions in Norway.

PMID- 11516198
TI  - Political strategy, business strategy, and the academic medical center: linking
      theory and practice.
AB  - The purpose of this paper is to link external political strategy theory to a
      specific health care setting-that of the academic medical center (AMC). Political
      strategy encompasses those activities undertaken by AMCs to acquire, develop, and
      use power (clout, influence, and credibility) to gain an advantage in situations
      of conflict. It should be differentiated from internal politics, a topic that
      will not be dealt with in this review. Political strategy should also be
      distinguished from but not divorced from competitive strategy. As political and
      social action can change the competitive landscape and the rules of competition,
      AMCs must become adept in issues management and stakeholder management. The focus
      on political strategy is a reflection of the enormous changes in the external
      environment that have impacted AMCs in recent years. These changes have often
      emerged out of political and social action and they impact significantly on the
      organization's more traditional business strategies. We suggest that a tighter
      alignment between political and business strategies in the future will help
      ensure organizational survival and success. This article reviews the literature
      and theory in corporate political strategy and illustrates the application of
      political strategy with examples of issues and problems faced by AMCs. Models of
      political strategy are well crafted, and this article concludes with succinct
      observations on the use of political strategies to enhance the business-based
      strategies of AMCs. Although the focus is on AMCs, the use of political
      strategies is applicable to any health care institution.

PMID- 11516199
TI  - Chemosensitization of pancreatic cancer by inhibition of the 26S proteasome.
AB  - BACKGROUND: Pancreatic cancer is extremely resistant to the induction of
      apoptosis by chemotherapies; agents that regulate sensitivity to apoptosis may
      lead to chemosensitization of pancreatic cancer. MATERIALS AND METHODS: MIA-PaCa
      2 human pancreatic cancer cells were treated in vitro with the 26S-proteasome
      inhibitor PS-341. Levels of the apoptosis-regulating proteins (BCL-2, BAK, and
      BAX) were determined by Western blotting. The effect of PS-341 on BCL-2 gene
      transcription was examined using a BCL-2 promoter/luciferase reporter construct.
      The chemosensitizing effect of PS-341 was determined by measurement of the
      cytotoxic effect of gemcitabine in the presence of PS-341 (10-1000 nM) using the
      MTT assay. A corresponding in vivo experiment using tumor xenografts in athymic
      mice was also performed. RESULTS: PS-341 decreased BCL-2, without effect on BAX
      or BAK. The downregulation of BCL-2 by PS-341 appears to be transcriptionally
      mediated. PS-341 induced apoptosis at high does (1000 nM) and increased the
      cytotoxicity of gemcitabine at low doses (10-100 nM). Xenograft growth was
      inhibited 59% by gemcitabine; the addition of PS-341 increased growth inhibition
      to 75%. CONCLUSIONS: Inhibition of the 26S proteasome disrupts the cellular
      content of key regulators of cell cycle progression and apoptotic control leading
      to increased sensitivity to standard chemotherapeutic agents, such as
      gemcitabine, in pancreatic cancer. Combination therapy may lead to better
      response rates.

PMID- 11516200
TI  - Breast cancer increases osteoclastogenesis by secreting M-CSF and upregulating
      RANKL in stromal cells.
AB  - BACKGROUND: Breast cancer metastasis to bone causes resorption of the mineralized
      matrix by osteoclasts. Macrophage colony stimulating factor (M-CSF)and receptor
      activator of the NF-kappaB ligand (RANKL) are produced by stromal cells and are
      essential for osteoclast formation. The human breast cancer cell line, MDA-MB
      231, reliably forms bone metastases in a murine model and stimulates osteoclast
      formation in culture. We hypothesized that MDA-MB-231 stimulates osteoclast
      formation through secretion of M-CSF and/or RANKL. MATERIALS AND METHODS: We
      cocultured MDA-MB-231 and a bone marrow derived cell line, UAMS-33, and evaluated
      the expression of M-CSF and RANKL mRNA. Osteoclast formation was assessed using
      these cells added to hematopoietic cell cultures. RESULTS: MDA-MB-231 exhibited
      constitutive expression of M-CSF mRNA. As expected, addition of recombinant M-CSF
      (30 ng/ml) and RANKL (30 ng/ml) to hematopoietic osteoclast precursors supported
      osteoclast formation, while the addition of soluble RANKL alone or MDA-231
      without added RANKL did not. Notably, coculture of MDA-231 with hematopoietic
      cells and added soluble RANKL stimulated significant osteoclast formation,
      indicating that MDA-231 served as an effective source for M-CSF. MDA-231 did not
      express RANKL. However, when cocultured with the murine bone marrow stromal cell
      line UAMS-33, RANKL expression was significantly increased in the latter cells.
      MDA-231 also stimulated osteoclast formation in coculture with UAMS-33 and
      hematopoietic cells. CONCLUSIONS: We conclude that MDA-MB-231 increases
      osteoclast formation by secreting adequate amounts of M-CSF protein and enhancing
      the expression of RANKL by stromal support cells. The ability to stimulate
      osteoclasts may explain the ability to metastasize to bone.

PMID- 11516201
TI  - The effect of a selective cyclooxygenase-2 inhibitor in extended liver resection
      with ischemia in dogs.
AB  - BACKGROUND: Pringle's procedure is commonly used during liver surgery, and it
      sometimes causes liver failure. Metabolites of arachidonic acid, which are
      converted by cyclooxygenase (Cox), are involved in ischemia-reperfusion injury.
      This study evaluated the effects of FK 3311, which selectively inhibits Cox-2, on
      ischemia-reperfusion injury during liver resection in dogs. MATERIALS AND
      METHODS: The animals were divided into four groups and subjected to 60 min of
      warm ischemia by partial inflow occlusion. The FK-treated groups (FK0.2: 0.2
      mg/kg, FK1: 1 mg/kg, FK3: 3mg/kg) received FK3311, and the control group received
      vehicle. Following reperfusion, the nonischemic lobes were resected and remnant
      liver function was evaluated. RESULTS: Tissue blood flow and serum glutamic
      oxaloacetic transaminase, glutamic pyruvic transaminase, and lactate
      dehydrogenase were significantly better in the FK1 and FK3 groups, especially
      FK1, than in the control group. Thromboxane B(2) was significantly lower in the
      FK1 and FK3 groups than in the control group. The level of 6-keto-prostaglandin
      F(1alpha) was significantly lower in the FK3 group and relatively unchanged in
      the FK1 group. Histological damage was milder in the FK1 group. There were
      significantly fewer polymorphonuclear neutrophils in the FK1 group than in the
      control group. CONCLUSIONS: FK3311 ameliorates the ischemia-reperfusion injury
      caused by Pringle's procedure during extensive liver resection. This agent may be
      clinically useful in extended liver surgery involving vascular isolation.

PMID- 11516202
TI  - Ex vivo host response to gastrointestinal cancer cells presented by autologous
      dendritic cells.
AB  - BACKGROUND: Dendritic cells (DCs) capture apoptotic tumors and cross-present
      their antigens in the MHC class I and class II pathways for recognition by CD4+
      and CD8+ T lymphocytes. Here we have tested the ability of fresh surgically
      resected colon and gastric cancer tumors to specifically activate host T
      lymphocytes when presented by autologous DCs. METHODS: DCs derived from adherent
      blood mononuclear cells of five patients, after a 7-day culture with GM-CSF and
      IL-4, were exposed to apoptotic autologous tumor (AAT) or apoptotic autologous
      peritumor normal (AAN) cells and cultured 24 h with monocyte-conditioned medium
      to achieve full DC maturation. Tumor-specific response was evaluated as single
      cell cytokine release in an enzyme-linked immunospot (ELISPOT) and as
      cytotoxicity in a cold target inhibition (51)Cr-release assay. RESULTS: AAT-DCs
      induced specific IFN-gamma by T lymphocytes of two patients (rectal and gastric
      cancer), whereas in another two patients (rectal and gastric cancer) this
      response was depressed with a similar tumor-specific pattern and in one patient
      (rectal cancer) there was no response. Activation of IFN-gamma release was
      accompanied by tumor cytotoxicity and both responses were enhanced by IL-12,
      indicating the functional integrity of patients' lymphocytes. CONCLUSION: These
      data show that T-cell memory against rectal/gastric carcinoma antigens can be
      triggered by tumor-loaded autologous DCs. However, escape mechanisms may exist
      among tumors of the same histological origin that can inhibit this host response.
      A DC-based antitumor immunological monitoring assay with autologous tumor
      biopsies may allow patients to be screened to determine those who are suitable
      candidates for immune-based immunotherapy.

PMID- 11516203
TI  - Large-scale isolation of sinusoidal endothelial cells from pig and human liver.
AB  - OBJECTIVE: Hepatic in vitro studies, like those on hypoxia/reperfusion injury in
      liver transplants, demand large numbers of cultivated sinusoidal endothelial
      cells (SECs). In this article, we present and evaluate a new method for the
      isolation of SECs from porcine and human livers. METHODS: SECs were isolated
      employing a four-step collagenase perfusion. The sinusoidal character of the
      cells was validated by transmission and scanning electron microscopy, exclusion
      of Weibel-Palade bodies and factor VIII-related antigen, expression of scavenger
      receptor, and incorporation of latex beads. RESULTS: In 23 pigs, an average of 9
      x 10(4) SECs were harvested from each liver. Cells were cultivated under standard
      conditions, as well as in multilayer cocultures of isolated SECs and hepatocytes
      in a "sandwich" configuration. Standard cultures showed an average of 90% SECs in
      primary cultures and 100% SECs after the first passage. The possibility of
      isolation of SECs from human livers was demonstrated in eight cases. CONCLUSION:
      With the four-step collagenase perfusion it is possible to easily isolate large
      numbers of viable and pure SECs from one organ. A further advantage is the
      possibility of isolating hepatocytes from the same organ.

PMID- 11516204
TI  - Hox D3 expression in normal and impaired wound healing.
AB  - BACKGROUND: We have previously shown that Hox D3 and Hox B3 can promote
      angiogenesis. As angiogenesis is essential for wound healing, we examined
      expression of these genes in the vasculature following wounding in normal and
      genetically diabetic adult mice with impaired healing. METHODS: In situ
      hybridization was performed on tissues taken 0, 1, 4, 7, and 14 days following
      administration of linear wounds in wild-type and genetically diabetic mice.
      Expression of Hox D3 and Hox B3, angiogenesis, and synthesis of type I collagen
      were assessed in the wound. RESULTS: Hox B3 was expressed in endothelial cells
      (ECs) of both medium and small vessels in unwounded tissue, whereas little Hox D3
      was detected in resting ECs. Hox D3 expression was significantly upregulated by 1
      day after wounding in ECs of vessels immediately adjacent to the wound site, and
      expression was maintained for at least 7 days. In the diabetic mice, expression
      of Hox B3 was similar to that of wild-type mice. In contrast, expression of Hox
      D3 in ECs was significantly lower and delayed during wound repair in diabetic
      mice. In cultured microvascular ECs, Hox D3 selectively induced high levels of
      collagen I mRNA expression. Hox D3-deficient wounds of diabetic animals also
      displayed a reduction in expression and deposition of type I collagen.
      CONCLUSIONS: These results suggest that reduced angiogenesis and type I collagen
      in diabetic mice with impaired wound healing may be related to deficient Hox D3
      expression, and restoring Hox D3 expression may enhance angiogenesis and wound
      repair.

PMID- 11516205
TI  - The difference in E-cadherin expression between nonvascularized and vascularized
      nerve grafts: study in the rat sciatic nerve model.
AB  - BACKGROUND: We investigated the expression of E-cadherin during nerve
      regeneration after nonvascularized and vascularized nerve grafts. MATERIALS AND
      METHODS: We used the rat sciatic nerve model. E-cadherin expression was detected
      by Western blot analysis and immunofluorescent staining with anti E-cadherin
      monoclonal antibody. The level of E-cadherin expression was calculated as the
      amount relative to that of E-cadherin expression of normal control nerve.
      Furthermore, repair of the neural tissue structure was examined by toluidine blue
      staining. RESULTS: In both cases, the level of E-cadherin expression decreased at
      first, and then gradually increased. The maximum level was 1.61 +/- 0.066-fold in
      the nonvascularized nerve graft and 2.254 +/- 0.071-fold in the vascularized
      nerve graft. From the 1st to the 16th postoperative weeks, the level of E
      cadherin expression in the vascularized nerve graft was significantly higher than
      that in the nonvascularized nerve graft. In the immunofluorescent staining, E
      cadherin expression was almost negative or decreased immediately after the
      operation, but the degree of expression was gradually increased in Schwann cells.
      The degree of E-cadherin expression in the vascularized nerve graft was greater
      than that in the nonvascularized nerve graft. In toluidine blue staining, the
      velocity of tissue repair was more rapid in the vascularized nerve graft than in
      the nonvascularized graft. CONCLUSION: These results demonstrate that the E
      cadherin expression of grafted nerve was increased during the nerve regeneration,
      and the expression was mainly observed in Schwann cells. Because the level of E
      cadherin expression was significantly higher in the vascularized nerve graft than
      in the nonvascularized nerve graft, the level of E-cadherin expression may affect
      the rapidity of nerve regeneration.

PMID- 11516206
TI  - Hyperbaric oxygenation after portal vein emobilization for regeneration of the
      predicted remnant liver.
AB  - BACKGROUND: Liver failure often develops after extensive liver resection.
      Preoperative portal vein embolization to induce compensatory hypertrophy in the
      predicted remnant liver decreases clinical complications after hepatectomy. The
      aim of this study was to examine whether hyperbaric oxygenation (HBO) after
      portal vein embolization increases compensatory hypertrophy of the predicted
      liver remnant. We performed portal vein ligation and HBO in rats to investigate
      whether HBO after portal vein embolization increases compensatory hypertrophy of
      the predicted remnant liver. METHODS: Rats were divided into four groups that
      underwent (1) laparotomy only (control group); (2) right portal vein ligation
      (RPL group); (3) RPL followed by HBO at 2 atm (HBO-2 atm group; 1 h/day, 5
      days/week for 2 weeks); or (4) RPL followed by HBO at 3 atm (HBO-3 atm group).
      Laparotomy was repeated after 2 weeks in each group; serum levels of albumin and
      hepatocyte growth factor (HGF) were measured, and the ratio of the weights of
      nonligated to ligated hepatic segments and the percentage of hepatocytes
      expressing proliferating cell nuclear antigen (PCNA) in ligated hepatic segments
      were determined. RESULTS: In rats that had received HBO after RPL, serum levels
      of HGF, weight ratios of nonligated to ligated hepatic segments, and the
      percentage of PCNA-positive hepatocytes in nonligated liver were significantly
      higher than those in the control group. Furthermore, rats that had undergone 3
      atm HBO after RPL had significantly higher serum levels of HGF and percentages of
      PCNA-positive hepatocytes in nonligated hepatic segments. CONCLUSIONS:
      Preoperative HBO after portal vein embolization may be useful for inducing
      compensatory hypertrophy of the predicted remnant liver.

PMID- 11516207
TI  - Expression of intercellular adhesion molecule-1 in the cortex of preserved rat
      kidneys.
AB  - BACKGROUND: Prolonged cold ischemia has been shown to be an important factor in
      the development of posttransplant renal dysfunction. The exact mechanisms have
      not been completely defined. The expression of intercellular adhesion molecule-1
      (ICAM-1) (CD 54) in rat kidneys stored in University of Wisconsin (UW) solution
      was studied in an attempt to correlate ischemia time with immunogenicity of the
      graft. METHODS: Kidneys from male Lewis rats were perfused with UW solution,
      removed, and bathed in UW solution at 4 degrees C for 4, 12, 24, and 48 h. For
      the evaluation of expression of ICAM-1, immunohistochemical staining, Western
      blotting, and semiquantitative reverse transcriptase-polymerase chain reaction
      (RT-PCR) were performed. RESULTS: Immunohistochemical staining in normal,
      nonischemic kidneys revealed that glomerular capillaries expressed ICAM-1 but
      that tubular cells did not. The preserved kidneys were analyzed by
      immunohistochemistry, Western blotting, and semiquantitative RT-PCR and showed
      increased transcription and expression of ICAM-1 in the cortex of the kidney.
      Expression reached a maximum at 24 h and declined at 48 h. The ICAM-1 protein
      expression in the preserved kidney cortex relative to control kidneys was
      increased at 4 h (1.68 +/- 0.60-fold of control kidneys, P = 0.06), 12 h (2.38 +/
      0.90-fold, P = 0.02), 24 h (3.70 +/- 1.29-fold, P = 0.01), and 48 h (2.00 +/-
      0.54-fold, P = 0.01). The messenger RNA expression (the ratio of ICAM-1 to
      glyceraldehyde-3-phosphate dehydrogenase) in preserved kidneys cortex relative to
      control kidneys was increased at 4 h (1.19 +/- 0.14-fold of control kidneys), 12
      h (1.38 +/- 0.16-fold), 24 h (1.77 +/- 0.29-fold), and 48 h (1.19 +/- 0.12-fold)
      (P < 0.05 for all time points). CONCLUSIONS: We conclude that cold preservation
      of rat kidneys in UW solution induces increasing levels of ICAM-1 cell surface
      expression and gene transcription. Further study is necessary to determine if
      this increase in adhesion molecule expression increases the immunogenicity of the
      allograft and contributes to the development of posttransplant renal dysfunction.

PMID- 11516208
TI  - Expression of aminopeptidase N in bile canaliculi: a predictor of clinical
      outcome in biliary atresia and a potential tool to implicate the mechanism of
      biliary atresia.
AB  - BACKGROUND: Only a few studies on extrahepatic biliary atresia (BA) have reported
      that the morphological changes of bile canaliculi could predict the clinical
      outcome after portoenterostomy and provide differential diagnosis of neonatal
      jaundice. Aminopeptidase N (APN) is an ectoenzyme of bile canaliculi that is
      involved in bile secretion. In this study, we tried to see whether APN of bile
      canaliculi had a significant role in BA. PATIENTS AND METHODS: We used monoclonal
      antibody 9B2 to compare the expression of APN in livers with BA, neonatal
      hepatitis, and choledochal cysts, as well as in nontumorous portions of pediatric
      hepatic livers with tumors. The expression of APN in fetuses, preterm babies, and
      term neonates was also studied. RESULTS: A high degree of 9B2 expression in BA
      was closely related to poor outcome. Cholestasis in choledochal cysts, rather
      than neonatal hepatitis, made 9B2 expression stronger. Increasing expression of
      9B2 from fetuses to neonates was noted and the degree of 9B2 expression was
      similar between term neonates and nontumorous portions of pediatric livers with
      tumors. Interestingly, some cases of BA had 9B2 expression like that of preterm
      babies. CONCLUSIONS: APN of bile canaliculi progressively develops from fetuses
      to neonates and is well developed in neonates. APN can be induced to stronger
      expression by obstructive jaundice. The amount of expression of APN of bile
      canaliculi in BA is a predictor of clinical outcome and may be a tool for
      implicating the mechanism of BA.

PMID- 11516209
TI  - Development of an animal model for assessment of the hemostatic efficacy of
      fibrin sealant in vascular surgery.
AB  - PURPOSE: Sustained hemostatic function of fibrin sealant (FS) is crucial when it
      is used in cardiovascular surgery. The purpose of this study was to develop a
      model that can determine the long-term hemostatic efficacy of tissue sealants in
      a vascular surgery. METHODS: To determine the ability of the model to detect
      differences in FS performance, various concentrations of FS were prepared and
      tested. Tensile strength of FS clots was determined in vitro using a tensiometer.
      Laparotomy was performed on 49 anesthetized rabbits, and a segment of the aorta
      was occluded, transected, and then sutured in an end-to-end fashion with four or
      eight interrupted 9-O sutures. The four-suture repair was covered with FS or
      placebo, and blood flow restored. Spilled blood was absorbed with gauze and
      weighed to estimate blood loss. Four weeks after surgery the animals were
      euthanized and the vessels recovered for histology. RESULTS: Average tensile
      strength of FS clots at 120, 90, and 60 mg/ml topical fibrinogen complex (TFC)
      concentration was 0.42 +/- 0.07 N, with no significant difference among them. The
      lowest TFC concentration, 30 mg/ml, produced weaker clots than either 120 or 90
      mg/ml (P < 0.05). All rabbits with four-suture anastomoses that were treated with
      placebo bled to death after the vessel was unclamped (n = 6). Treatment of suture
      line with standard FS concentration (120 mg/ml TFC, n = 8) sealed the anastomosis
      and prevented blood loss. Hemostasis was sustained for 4 weeks, allowing vascular
      healing. All rabbits with the eight-suture anastomosis survived the operation but
      lost 42 +/- 9.2 ml blood (n = 5). Hemostatic efficacy of FS was unchanged when
      TFC was diluted to 90 mg/ml (n = 6) but further dilution to 60 mg/ml with water
      (n = 8) produced significantly less effective clots, with an average blood loss
      of 5.5 +/- 7.6 ml (P < 0.05) and two fatal clot failures postoperatively. When FS
      was diluted to 60 mg/ml TFC with a buffer, it maintained its hemostatic strength
      (n = 6). Further TFC dilution to 30 mg/ml led to consistent bleeding with an
      average blood loss of 35.3 +/- 10.3 ml (P < 0.001, n = 6). CONCLUSIONS: The four
      suture anastomosis of rabbit aorta offers a consistent and reliable method for
      evaluating the short- and long-term hemostatic efficacy of FS products. This
      model is not only able to determine the functional differences in various
      concentrations of FS, but it is also sensitive to detect the subtle changes in FS
      preparation (e.g., medium composition) that is not detected by in vitro testing.

PMID- 11516211
TI  - Accuracy of intravascular ultrasound for diameter measurement of phantom
      arteries.
AB  - BACKGROUND: Uniplanar quantitative angiography (QA) is the standard method for
      measuring vessel diameter during surgical and endovascular procedures.
      Intravascular ultrasound (IVUS), a relatively new technology, is another means of
      obtaining this measurement. This study was designed to validate the accuracy of
      these two modalities by comparing each to direct caliper measurement, the gold
      standard, using phantom femoral artery segments (PAS). MATERIALS AND METHODS: PAS
      diameter was measured with a 12.5-MHz mechanically rotating IVUS catheter (Boston
      Scientific Corp.) and QA (OEC Corp.) was compared to the direct caliper
      measurement (Mitutoyo Corp.) at 60 different locations within PAS. At each
      location minimal lumen diameter and perpendicular lumen diameter were measured
      and their mean was calculated. The intraclass correlation coefficients (ICCC)
      between direct caliper measurement and IVUS and uniplanar and biplanar
      angiography were calculated. Fisher's Z transformation was used to compare the
      correlation coefficients. RESULTS: The ICCC for IVUS was 0.89. The ICCCs for
      uniplanar and biplanar angiography were 0.73 and 0.82, respectively. IVUS
      correlated more closely with direct caliper measurement than uniplanar and
      biplanar angiography (P = 0.00008, 0.02) Biplanar angiography correlated more
      closely with direct caliper measurement than uniplanar angiography (P = 0.04).
      CONCLUSIONS: IVUS more accurately measures lumen diameter than uniplanar or
      biplanar angiography. Diameter measurement with biplanar angiography is more
      accurate than uniplanar angiography.

PMID- 11516210
TI  - Contraction coupled endothelial nitric oxide release: a new paradigm for local
      vascular control?
AB  - INTRODUCTION: Nitric oxide (NO), a potent vasodilator, is presumed to be
      constitutively released in most mammalian blood vessels. In isolated rat thoracic
      aorta, however, hemoglobin (Hb), a nitric oxide scavenger, elicited contraction
      only when the vessels were precontracted with an alpha adrenergic agonist. Does
      vascular contraction induce endothelial NO release? METHODS: Thoracic aortic
      rings from male Sprague-Dawley rats were prepared with or without the
      endothelium. Vessel rings were contracted with several distinct types of
      contractile agonists and NO release was probed using a Hb contraction assay in
      the presence and absence of nitro-l-arginine methyl ester (NAME), a NO synthase
      inhibitor. RESULTS: In vessel rings precontracted with norepinephrine, potassium
      chloride, arginine vasopressin, prostaglandin F(2alpha), or serotonin, Hb
      elicited significant additional contractions. In contrast, Hb failed to elicit
      significant contractions in vessel rings without the functional endothelium or
      vessels pretreated with NAME. The Hb mediated additional contraction was not
      inhibited by calmidazolium, a calmodulin antagonist, and protein kinase
      inhibitors staurosporine and 2,5-dihydromethylcinnamate. Intercellular gap
      junction inhibitor 2,3-butanedione monoxime at a low dose (<2 mM) significantly
      attenuated the NE/Hb mediated contractions but at a high dose (>15 mM) completely
      prevented both contractions. The contraction coupled NO release may be mediated
      through a mechanism distinct from the Ca(2+)-calmodulin-dependent endothelial NOS
      pathway. CONCLUSIONS: In the isolated rat thoracic aorta, endothelial NO release
      may be coupled to contractile stimulus. This vascular property appears to render
      a unique local control mechanism independent of baroreflex and other central
      mechanisms.

PMID- 11516212
TI  - Institutional validation of breast cancer treatment guidelines.
AB  - Several groups have developed clinical guidelines for the management of breast
      cancer, yet little data exist regarding their validation. Therefore, we examined
      the effect of published National Comprehensive Cancer Network (NCCN) guidelines
      for invasive breast cancer on survival, quality of life (QOL), and hospital cost.
      From 260 consecutive breast cancer patients, 129 patients were identified for
      analysis: 93 patients (72%) were treated according to the guidelines (NCCN+),
      while the treatment of 36 patients (28%), with a similar stage distribution,
      deviated from the guidelines (NCCN-). Patients were excluded from analysis with a
      diagnosis of carcinoma in situ, inflammatory cancer, stage IV disease, and
      comorbid conditions that affected treatment. The 5-year survival was 87.6% for
      the NCCN+ patients versus 83.3% for NCCN- patients (P = 0.319 by Kaplan-Meier).
      Twelve QOL parameters were evaluated using a Likert-type scale (1 = severe and 5
      = none). NCCN+ patients had a cumulative QOL score of 4.18 +/- 0.08 versus 4.24
      +/- 0.14 for NCCN- patients (P = 0.745). Treatment-related costs were $20,300 +/-
      1800 for NCCN+ patients versus $59,700 +/- 25,200 for NCCN- patients (P = 0.016
      by t test). Although deviation from NCCN breast cancer guidelines had no effect
      on perceived quality of life or survival, there was a significant decrease in
      cost in the NCCN+ group. These findings suggest that adherence to NCCN guidelines
      can significantly reduce the cost of breast cancer care without adversely
      affecting either survival or quality of life.

PMID- 11516213
TI  - Interleukin-10 prevents loss of tone of rat skeletal muscle arterioles exposed to
      endotoxin.
AB  - BACKGROUND: The anti-inflammatory cytokine interleukin-10 (IL-10) is known to
      inhibit the development of septic shock in animal models. This study was
      conducted to investigate the effect of IL-10 on the loss of vascular tone during
      exposure to endotoxin. Unlike numerous proinflammatory cytokines, the effects of
      IL-10 at the level of the microvasculature have not been previously studied.
      MATERIALS AND METHODS: First-order rat cremasteric arterioles (n = 27) were
      placed in an isolated vessel preparation and allowed to achieve spontaneous tone.
      An opened segment of thoracic aorta was then placed upstream from the arteriole
      in the superfusion line. The resistance arteriole of this in-series model, in
      contrast to the isolated arteriole alone, demonstrates a significant loss of tone
      when exposed to endotoxin. Following 1 h of equilibration in the presence or
      absence of IL-10 (20 ng/ml), the aorta and arteriole were then superfused with
      2.5 microg/ml endotoxin or physiologic buffer for 60 min and serial arteriolar
      diameter measurements were recorded. Group 1 was exposed to endotoxin only, Group
      2 was a time control, and Group 3 was pretreated with IL-10 prior to endotoxin
      exposure, while Group 4 was a control pretreated with IL-10 only. RESULTS: After
      the 60-min equilibration period there were no differences among the four groups
      in arteriolar tone. At t = 120 min, the percentage of tone in the control group
      was 43.6 +/- 3% (mean +/- SEM) and this was not changed by treatment with IL-10
      (47.0 +/- 7% tone). Endotoxin alone caused arteriolar tone to fall to 31.4 +/- 3%
      (P < 0.05). However, endotoxin applied to arterioles pretreated with IL-10 was
      without effect (47.5 +/- 2%). CONCLUSIONS: Resistance arterioles pretreated with
      IL-10 maintain vascular tone during endotoxin exposure. We conclude that IL-10
      pretreatment prevents loss of vascular tone of isolated arterioles exposed to
      endotoxin.

PMID- 11516214
TI  - Relationship of hydraulic impedance and elasticity in the pulmonary artery of
      maturing newborn pigs.
AB  - The current study determined the dynamic stress-strain elastic moduli (E(Y)) and
      characteristic impedances (Z(0(2-7Hz))) of the main pulmonary artery in open
      chest, anesthetized newborn pigs at 2 days, 2 weeks, and 3 months of age. E(Y)
      and Z(0(2-7Hz)) were compared to those values derived from the Womersley and
      Moens-Korteweg equations (denoted E(W-MK) and Z(0W-MK), respectively) to test the
      validity of these equations in describing the elasticity of the intact newborn
      pulmonary artery. E(Y) was defined as the ratio of stress to strain. The current
      study hypothesized that: (1) E(Y) and E(W-MK) are numerically similar, and
      therefore the Womersley and Moens-Korteweg equations accurately describe the
      viscoelastic properties of the main pulmonary artery of the newborn pig, and (2)
      that both E(Y) and Z(0) are elevated at birth and undergo a steady decline with
      maturation. E(Y) was not significantly different from E(W-MK), while Z(0(2-7Hz))
      was nearly identical to Z(0W-MK) in all groups. The elastic modulus peaked (P <
      0.001) in 2-week-old pigs compared with both younger and older animals, while
      Z(0(2-7Hz)) decreased with increasing age (48 h = 1237 +/- 251 [SEM] dyn s cm(
      5), 2-week = 433 +/- 95 dyn s cm(-5), 3 month = 162 +/- 17 dyn s cm(-5), P <
      0.001). These experiments validate the Womersley and Moens-Korteweg equations as
      accurately describing the elastic properties of the intact newborn pig pulmonary
      artery. These data also demonstrate that a diminution in Z(0) may occur even with
      increased wall stiffness, as observed in our 2-week-old pigs.

PMID- 11516215
TI  - Lipopolysaccharide: neutralization by polymyxin B shuts down the signaling
      pathway of nuclear factor kappaB in peripheral blood mononuclear cells, even
      during activation.
AB  - BACKGROUND: There have been many studies on anti-lipopolysaccharide (LPS) agents
      and LPS-neutralizing agents; however, there have been no reports on the changes
      in clinical status and mediators that occur when these agents are used. Polymyxin
      (PMX) (treatment using a column containing polymyxin B-immobilized fiber) removed
      circulating endotoxin, and reduced various cytokines within 120 min, even in
      patients with high levels of plasma cytokines. Our purpose was examine the
      mechanisms of PMX treatment by which plasma cytokines are reduced by endotoxin
      neutralization with polymyxin B, even during therapy for sepsis and/or endotoxin
      shock. METHODS: We studied the interaction between nuclear factor kappaB (NF
      kappaB) binding activity and tumor necrosis factor alpha (TNF-alpha) secretion in
      an experimental system using LPS-stimulated human peripheral blood mononuclear
      cells (PBMCs), after neutralization of LPS with polymyxin B. PBMCs were incubated
      with LPS in vitro, and TNF-alpha secretion and NF-kappaB activation were
      assessed. We then studied the changes in NF-kappaB activation and TNF-alpha
      secretion when both polymyxin B and LPS were added simultaneously and when
      polymyxin B was added after 30 or 120 min of incubation with LPS. RESULTS:
      Immediate inhibition of NF-kappaB binding activity and suppression of TNF-alpha
      secretion were observed after LPS neutralization with polymyxin B regardless of
      whether PBMCs were already producing TNF-alpha. CONCLUSIONS: These findings may
      indicate one of the mechanisms operating in the clinical changes that occur after
      circulating endotoxin removal, and are likely to have therapeutic value, even for
      patients with high proinflammatory cytokine levels.

PMID- 11516216
TI  - Effect of 7,12-dimethylbenz[a]anthracene (DMBA) on gut glutathione metabolism.
AB  - BACKGROUND: One mechanism of the mammary carcinogenesis of 7,12
      dimethylbenz[a]anthracene (DMBA) is thought to be the generation of reactive
      oxygen species known to play an important role in initiation and progression. We
      hypothesized that DMBA would disrupt gut glutathione (GSH) metabolism and this
      disruption would correlate with mammary cell carcinogenesis. METHODS: Sixty-four
      Sprague-Dawley rats were randomized to the DMBA versus control groups. At age 50
      days, rats were gavaged with a one-time dose of 20 mg DMBA or sesame oil. Rats
      from each group were sacrificed at 1 week (n = 16), 2 weeks (n = 16), 4 weeks (n
      = 16), and 11 weeks (n = 16). Tumor appearance, arterial and gut GSH
      concentration, and gut GSH extraction were measured over time. RESULTS: Gut GSH
      extraction (normally negative; production) was significantly depressed over the
      time points, even showing uptake (positive extraction) at Weeks 1 and 2. Tumors
      developed in all animals in the DMBA group by Week 11. CONCLUSIONS: A one-time
      oral administration of DMBA has a significant and prolonged depressive effect on
      gut GSH production that has not previously been described. These data support the
      hypothesis that the carcinogenic effect of DMBA is mediated, at least in part, by
      oxidative damage and that the disruption of gut GSH metabolism may play a greater
      role in carcinogenesis than previously realized.

PMID- 11516217
TI  - Radiation hormesis: an ecological and energetic perspective.
AB  - Organisms in natural habitats are exposed to an array of environmental stresses,
      which all have energetic costs. Under this ecological scenario, hormesis for
      ionizing radiation becomes an evolutionary expectation at exposures substantially
      exceeding background. This conclusion implies that some relaxation of radiation
      protection criteria is worthy of serious consideration.

PMID- 11516218
TI  - Is multiple sclerosis caused by a silent infection with malarial parasites? A
      historico-epidemiological approach: part I.
AB  - Though many details are known about the epidemiology of multiple sclerosis (MS),
      its aetiology has remained an enigma. To find a solution to this problem, the
      concept of so called 'anophelism without malaria' was put on trial. 'Anophelism
      without malaria' is a basic assumption of the epidemiology of malaria. It means
      that there is no transmission of malaria in the temperate zone, although the
      insect vector (the different species of anopheles) can be found nearly
      everywhere. Starting with the results from blood tests of five patients suffering
      from MS which indicate an infection with plasmodia, the old hypothesis of the
      malarial aetiology of MS (Mannaberg 1899) is reappraised and compared with
      today's pathological findings. A comparison of the old map of malaria with the
      later distribution of MS in the USA has been made, supporting the assumption that
      an infection with plasmodia in early childhood prevents a later disease, while a
      silent infection at the time of adolescence or later is its cause.

PMID- 11516219
TI  - Is multiple sclerosis caused by a silent infection with malarial parasites? A
      historico-epidemiological approach: part II.
AB  - The comparison between the old map of malaria and the later distribution of
      multiple sclerosis (MS) first carried out in the USA (Part I) is continued in
      Europe. The Italian 'dilemma' (Kurtzke), meaning the disappearance of the north
      south gradient in Italy by recent surveys, can be solved when considering the
      dependence of malaria transmission in relation to the altitude. Further, the high
      prevalence of MS in earlier times in Mississippi, Louisiana and in the former
      province of Lucania in Italy can be explained by preceding epidemics of malaria.
      Brickner's therapeutic trial with quinine in cases of MS patients is reevaluated,
      and by this the Jarisch-Herxheimer reaction is shown to exist in MS too. The
      possible significance of the old and rather forgotten provocative methods for the
      diagnosis of latent malaria is discussed.

PMID- 11516220
TI  - Nitric oxide and free stable nitroxyl radicals in the mechanism of biological
      action of the spin-labeled compounds.
AB  - A comparison of more important physical, chemical and biological properties of
      the nitric oxide (NO) and free stable nitroxyl radicals (nitroxides) on the base
      of their structural similarity is made in the article. The active moiety in the
      nitroxide molecule represents a sterically hindered nitric oxide. The mechanisms
      of biological action of the nitroxides and especially of their derivatives with
      antitumor agents from the groups of nitrogen mustards, nitrosoureas, aziridines
      and triazenes (spin-labeled compounds) is explained through the biological
      activities of sterically hindered NO. Similarly to NO, nitroxides also can react
      with superoxide anion radical (O(2)(-)), they possess superoxide dismutase (SOD)
      mimetic action. While the interaction of NO with O(2)(-)yields very toxic
      peroxynitrite (ONOO(-)), its formation is strongly limited in the presence of a
      nitroxide. It is known that the nitrosourea antitumor drugs, like lomustine
      (CCNU) and carmustine (BCNU), showed high general toxicity, one of the reasons
      for that probability is the formation of NO, and subsequently of ONOO(-), during
      their metabolism. The biological investigations of the nitroxides showed their
      considerably lower general toxicity that could be explained with the SOD-mimetic
      action of the nitroxide present in their molecule.

PMID- 11516221
TI  - Neutrophil degranulation: coactivation of chemokine receptor(s) is required for
      extracellular nucleotide-induced neutrophil degranulation.
AB  - Extracellular nucleotide-induced stimulation of leukocytes and subsequent
      adhesion to endothelium plays a critical role in inflammatory diseases. The
      extracellular nucleotides stimulate a P2Y receptor on human PMN with the
      pharmacological profile of the P2Y2 receptor. Followed by generation of
      arachidonic acid, subsequently metabolized by 5 lipoxygenase forming the
      leukotrienes (LT). Of the several LTs generated, LTB(4)is a potent chemokine and
      upon its release binds to the PMN in an autocrine manner leading to the PMN
      degranulation. It is known that LTB(4)causes neutrophil degranulation through its
      receptor specific binding while the molecular mechanism remains not known at
      present. However, it is not known whether any LTB(4)receptor exists in cytoplasm
      in any given cell type and also, the existence of any other signaling cascade for
      the extracellular nucleotide-induced neutrophil degranulation. Based on the few
      direct experimental and numerous circumstantial evidence, it is conceivable that
      the extracellular nucleotides require LT generation, as an essential intermediate
      for mediating neutrophil degranulation.

PMID- 11516222
TI  - Does supplemental creatine prevent herpes recurrences?
AB  - While functioning as a general practitioner at the Camp Pendleton Marine Base,
      the first author treated numerous patients with recurrent genital herpes.
      Beginning in 1998, a number of these patients failed to return for periodic
      acyclovir therapy. Inquiries revealed that these patients had all commenced
      supplemental creatine after their last outbreak, and had experienced no further
      outbreaks. A literature search uncovered a report that cyclocreatine, a synthetic
      compound structurally and functionally homologous to creatine, inhibits the
      replication of cytomegalovirus, varicella-zoster, and herpes simplex types 1 and
      2, in low millimolar concentrations; furthermore, dietary cyclocreatine reduces
      morbidity and mortality in mice infected with HSV-2. The fact that both creatine
      and cyclocreatine exert neuroprotective and cancer-retardant effects in rodents,
      encourages the speculation that creatine shares the anti-viral activity of
      cyclocreatine. Pilot studies to assess the impact of creatine loading on
      recurrence of oral and genital herpes appear warranted; the impact of creatine on
      shingles occurrence in high-risk patients could also be explored. Although
      initially conceived as an aid to athletic performance, creatine loading may prove
      to have broad preventive and therapeutic applications.

PMID- 11516223
TI  - Versatile cytoprotective activity of lipoic acid may reflect its ability to
      activate signalling intermediates that trigger the heat-shock and phase II
      responses.
AB  - Although lipoic acid (LA) and its reduced derivative (DHLA) have broad
      antioxidant activity, it seems unlikely that this can adequately explain the
      remarkable neuroprotective effects of LA observed in rodents and in diabetic
      patients. It is proposed that this protection is mediated, in large measure, by
      induction of various protective proteins. More specifically, there is some reason
      to suspect that LA can trigger both heat-shock and phase II responses, and that
      LA may achieve this by catalyzing the formation of intramolecular disulfides in
      certain signalling proteins that function as detectors of oxidants and/or
      electrophiles. This hypothesis is readily testable, and, if true, would suggest
      that LA may have general utility for preventing or treating neurodegenerative
      disorders, and possibly also may retard the adverse impact of aging on brain
      function. This model also predicts that LA should have anticarcinogenic activity.

PMID- 11516224
TI  - Does a vegan diet reduce risk for Parkinson's disease?
AB  - Three recent case-control studies conclude that diets high in animal fat or
      cholesterol are associated with a substantial increase in risk for Parkinson's
      disease (PD); in contrast, fat of plant origin does not appear to increase risk.
      Whereas reported age-adjusted prevalence rates of PD tend to be relatively
      uniform throughout Europe and the Americas, sub-Saharan black Africans, rural
      Chinese, and Japanese, groups whose diets tend to be vegan or quasi-vegan, appear
      to enjoy substantially lower rates. Since current PD prevalence in African
      Americans is little different from that in whites, environmental factors are
      likely to be responsible for the low PD risk in black Africans. In aggregate,
      these findings suggest that vegan diets may be notably protective with respect to
      PD. However, they offer no insight into whether saturated fat, compounds
      associated with animal fat, animal protein, or the integrated impact of the
      components of animal products mediates the risk associated with animal fat
      consumption. Caloric restriction has recently been shown to protect the central
      dopaminergic neurons of mice from neurotoxins, at least in part by induction of
      heat-shock proteins; conceivably, the protection afforded by vegan diets reflects
      a similar mechanism. The possibility that vegan diets could be therapeutically
      beneficial in PD, by slowing the loss of surviving dopaminergic neurons, thus
      retarding progression of the syndrome, may merit examination. Vegan diets could
      also be helpful to PD patients by promoting vascular health and aiding blood
      brain barrier transport of L-dopa.

PMID- 11516225
TI  - Hepatothermic therapy of obesity: rationale and an inventory of resources.
AB  - Hepatothermic therapy (HT) of obesity is rooted in the observation that the liver
      has substantial capacities for both fatty acid oxidation and for thermogenesis.
      When hepatic fatty acid oxidation is optimized, the newly available free energy
      may be able to drive hepatic thermogenesis, such that respiratory quotient
      declines while basal metabolic rate increases, a circumstance evidently favorable
      for fat loss. Effective implementation of HT may require activation of carnitine
      palmitoyl transferase-1 (rate-limiting for fatty acid beta-oxidation), an
      increase in mitochondrial oxaloacetate production (required for optimal Krebs
      cycle activity), and up-regulation of hepatic thermogenic pathways. The possible
      utility of various natural agents and drugs for achieving these objectives is
      discussed. Potential components of HT regimens include EPA-rich fish oil,
      sesamin, hydroxycitrate, pantethine, L-carnitine, pyruvate, aspartate, chromium,
      coenzyme Q10, green tea polyphenols, conjugated linoleic acids, DHEA derivatives,
      cilostazol, diazoxide, and fibrate drugs. Aerobic exercise training and very-low
      fat, low-glycemic-index, high-protein or vegan food choices may help to establish
      the hormonal environment conducive to effective HT. High-dose biotin and/or
      metformin may help to prevent an excessive increase in hepatic glucose output.
      Since many of the agents contemplated as components of HT regimens are
      nutritional or food-derived compounds likely to be health protective, HT is
      envisioned as an on-going lifestyle rather than as a temporary 'quick fix'.
      Initial clinical efforts to evaluate the potential of HT are now in progress.

PMID- 11516227
TI  - Cellular configuration of DNA and cell division.
AB  - A hypothesis is presented concerning the configuration of DNA molecules in a cell
      nucleus. It is shown that this configuration leads to cell division and that the
      replication of DNA follows the Fibonacci numerical series. The fertilisation of
      an ovum cell by a sperm cell is discussed on the basis of the hypothesis along
      with considerations of the cloning of mammals. Also discussed is the initiation
      of rapid division of cells associated with the formation of cancerous conditions
      in cells.

PMID- 11516226
TI  - A model for potential tumor immunotherapy based on knowledge of immune mechanisms
      responsible for spontaneous abortion.
AB  - Attempts to treat various cancers by immunotherapy have been tried for about 50
      years. Most studies have focused on improving cytotoxic T lymphocyte (CTL)
      responses against various tumors. Immunotherapy has been both active and passive,
      and results have been modest at best. Spontaneous abortion (SAB) of pregnancies
      could in some ways resemble remission of a tumor. Both tumors and conceptusses
      are faced with a similar problem -- how to grow in a host in a vascular rich
      area, and yet escape immune surveillance despite both entities being an allogenic
      stimulus. In general, the fetus is far more immunogenic than a spontaneous tumor,
      and yet abortuses seem to avoid CTL responses but are sometimes invaded by
      natural killer (NK) cells. There are data suggesting that SAB will occur if there
      is inhibition of production of an immunosuppressive protein called progesterone
      induced blocking factor (PIBF). This protein inhibits NK cell cytolysis and
      influences TH2 cytokine dominance over TH1. If some tumors avoid NK cell
      destruction through a PIBF mechanism, perhaps an active rejection of these tumors
      could be achieved by inhibiting PIBF production by treating with a progesterone
      receptor antagonist. Passive immunization could also be considered by conjugative
      radionuclide or toxic chemical to a PIBF antibody which may be tumor specific
      since PIBF is not produced in normal tissue. The first step should be to see if
      PIBF can be detected in the peripheral circulation in patients with certain
      tumors.

PMID- 11516228
TI  - 'Cor placentale': placental intervillus/intravillus blood flow mismatch is the
      pathophysiological mechanism in severe intrauterine growth restriction due to
      uteroplacental disease.
AB  - The underlying pathophysiology in most cases of severe intrauterine growth
      restriction and pre-eclampsia is thought to be abnormal and inadequate conversion
      of the branches of the uterine arteries into low resistance uteroplacental
      vessels, due to poor extravillous trophoblastic invasion, leading to reduced
      intervillous blood flow. Since, in most vascular beds the main site of flow
      resistance is at the level of the small arteries/arterioles rather than the
      capillary bed itself it is likely that in cases of intrauterine growth
      restriction due to uteroplacental dysfunction with abnormal fetal umbilical
      artery flow velocity waveforms, the underlying pathological mechanism is
      primarily an initial reduction in intervillus flow leading to relative local
      hypoxia of some villus territories. This results initially in autocrine/paracrine
      mediated localized stem artery vasoconstriction to minimize
      intervillus/intravillus flow mismatch which, when widespread, will result in
      abnormal umbilical artery Doppler waveforms due to the globally increased
      resistance to fetoplacental flow. Since, a small reduction in vessel radius will
      result in an exponential increase in flow resistance and reduction in flow, the
      magnitude of stem vessel constriction need only be small to result in large
      changes in fetoplacental vascular haemodynamics. Thus, the underlying progressive
      pathology in this condition may be cardiac failure, secondary to chronic stem
      vessel vasoconstriction caused by abnormalities in oxygenation of the fetal
      respiratory system hence the term 'cor placentale' is proposed.

PMID- 11516229
TI  - Quantum cellular biology: a curious example of a cat.
AB  - In this paper, as a curious example of Schrodinger's cat, quantum cellular
      biology describes the similarity between a 'Schrodinger's cat' and a
      'Schrodinger's cat-like state' of a single cell made by the microcell fusion
      method. Mutations result from quantum processes involving molecules that cross
      over an energy barrier from one stable configuration to a different stable
      configuration. As we allow in principle for the aspects of this phenomena, this
      insight may suggest a new quantum cellular biology.

PMID- 11516230
TI  - Pheromones cause disease: pheromone/odourant transduction.
AB  - This paper compares two models of the sense of smell and demonstrates that the
      new model has advantages over the accepted model with implications for medical
      research. The accepted transduction model had an odourant or pheromone contacting
      an aqueous sensory lymph then movement through it to a receptor membrane beneath.
      If the odourant or pheromone were non-soluble, the odourant/pheromone supposedly
      would be bound to a soluble protein in the lymph to be carried across. Thus, an
      odourant/carrier protein complex physically moved through the receptor
      lymph/mucus to interact with a membrane bound receptor. After the membranous
      receptor interaction, the molecule would be deactivated and any
      odourant/pheromone-binding protein recycled. This new electrical chemosensory
      model being proposed here has the pheromone or other odourant generating an
      electrical event in the extra-cellular mucus. Before the pheromone arrives,
      proteins of the 'carrier class' dissolved in the receptor mucus slowly and
      continuously sequester ions. A sensed pheromonal chemical species sorbs to the
      mucus and immediately binds to the now ion-holding dissolved protein. The binding
      of the pheromone to the protein causes a measurable conformational change in the
      pheromone/odourant-binding protein, desequestering ions. Releasing the bound ions
      changes the potential differences across a nearby super-sensitive dendritic
      membrane resulting in dendrite excitation. Pheromones will be implicated in the
      aetiology of the infectious, psychiatric and autoimmune diseases. This is the
      third article in a series of twelve to systematically explore this contention
      (see references 1-9).

PMID- 11516231
TI  - Why the increases in upper respiratory problems?
AB  - The incidence of ear infections has roughly tripled in the last 25 years. Sinus
      infections and allergies also have increased. Asthma, triggered by chronic sinus
      infections and allergies, has paralleled the increases of otitis. These increases
      began in the early 1970s when antihistamines, decongestants, and combinations
      thereof, became available without prescription and were heavily advertised in the
      growing media of television. These drugs are designed to block the immune
      system's attempts to wash pollutants and irritants from the nasopharynx. The
      alternative is helping the immune system with this washing. I have used such a
      technique in my office for the past three years. Its rationale is discussed as
      well as my own experience.

PMID- 11516232
TI  - Sudden infant death syndrome requires genetic predisposition, some form of stress
      and marginal malnutrition.
AB  - Over the past 30 years or more, the problem of sudden, unexplained death in
      infants (SIDS) has made little headway. Many hypotheses have been offered but the
      basic cause remains elusive. The only successful prevention has been made by the
      supine sleeping posture. There is still, however, a hard core of unexplained
      incidents. There is evidence that certain stress factors are involved, and there
      is good evidence that the tragedy has a familial or genetic tendency. The third
      factor necessary for the event is inefficient oxidation in brain cells induced
      most commonly by marginal malnutrition in pregnancy or after birth. The absence
      of any one or more of these three factors decreases risk to the point of
      extinction. Anything that impedes healthy oxidation, or accelerates energy
      utilization through responding to stress, increases the risk greatly. Improving
      the biochemical mechanisms through appropriate nutrition is by far the best
      defense.

PMID- 11516233
TI  - Does body fat protect against negative moods in women?
AB  - An examination of the relationship between body mass index (BMI) and negative
      mood revealed an inverse relationship between BMI and negative mood symptoms
      (i.e., depression and negative affect scale scores) in women who were not taking
      oral contraceptives. The strength of the negative correlations between BMI and
      negative affect was uniformly higher on days of the menstrual cycle when estrogen
      levels are expected to be highest. Two interpretations are suggested. Given the
      positive relationship between estrogen levels and body fat, estrogen may have an
      effect on both body fat storage and negative affect. The cyclical release of
      estrogen may also have activational effects on negative affect. These findings
      have implications for common beliefs about the relationship between body size and
      emotional well-being, and provide converging evidence for the role of hormones in
      the regulation of mood.

PMID- 11516234
TI  - Mental retardation in Down syndrome: a hydrogen sulfide hpothesis.
AB  - Mental retardation is progressive in Down syndrome: individuals are born with
      normal intelligence which starts to decline linearly within the first year. This
      phenomenon can be observed with phenylalanine in patients with phenylketonuria,
      therefore it is compatible with metabolic intoxication. The toxic compound could
      be hydrogen sulfide. The amount of the compound is probably increased in Down
      syndrome by increasing active cystathionine beta synthase. This heuristic
      hypothesis requires further investigation.

PMID- 11516235
TI  - Is infection a major risk factor for preeclampsia?
AB  - Recently in an open population-based program composed of 15 354 pregnant women in
      Colombia we applied a biopsychosocial risk model, which permitted us to identify
      pregnant women at high risk of preeclampsia. 1443 (9.4%) of patients at high risk
      for developing preeclampsia received 450 mg of linoleic acid, and 1.5 g/day of
      calcium. Bacteriuria was identified in 1766 (11.5%) and vaginal infections in
      2150 (14.0%) of the pregnant women. These women received oral antibiotics for 10
      days. The incidence of low birthweight, preterm delivery and preeclampsia were
      reduced by 53% (6.2% vs 13.2%), 64.7% (1.8% vs 5.1%), and 52.5% (3.8% vs 8.0%)
      respectively, when compared with the incidence of the preceding five years. We
      believe that these dramatic reductions were due to early identification of risk
      factors, administration of nutritional supplements and principally by treatment
      of asymptomatic infections. Unfortunately, because of the study design it is not
      possible to confirm that infection was the major risk factor for preeclampsia in
      our population. However, we hypothesize that chronic subclinical infections may
      cause increased maternal cytokine levels sufficient to affect vascular
      endothelial function, and so prime individuals for the subsequent development of
      preeclampsia. This hypothesis can be tested in a more appropriately designed
      clinical trial to assess whether there is a relationship between infection,
      inflammation and preeclampsia.

PMID- 11516236
TI  - Radio-prevention of micrometastases.
AB  - In developed countries, the cancer incidence is about 150,000 cases per year and
      half of people with cancer may die from the extension of the primary tumour in
      secondary deposits. This disaster costs more than 2 billion euro per year. People
      with cancer are often treated with surgery and/or radiotherapy of localized
      primary tumour and chemo-prevention of occult disseminated micrometastases. Since
      chemotherapy essentially targets cycling tumour cells, quiescent micrometastases
      which may contain only one cell may escape. We previously reported that human
      melanoma clones with high metastatic potential and low gangliosides content
      appeared very radiosensitive to low-dose ionizing radiation both in culture and
      in immunosuppressed animals. This exquisite radiosensitivity was observed with
      the highly metastatic single cells which were resting at the time of irradiation.
      These data are consistent with the dose-response relationship for the
      radiotherapy of secondary deposits which appears linear with no threshold. Highly
      metastatic cells at an early stage of growth also appear very sensitive to
      chemicals and activated immune cells. We propose the medical hypothesis according
      to which the spread of resting micrometastases should be prevented by a single
      fraction of total-body irradiation delivered at a dose sufficiently low (below
      0.2 Gy) to avoid normal tissue radiotoxicity. Radio-prevention may complement
      standard treatments for patients with metastases and may be delivered even for
      patients in whom no distant metastases were detected on tumour diagnosis (M0
      stage).

PMID- 11516237
TI  - Does regular ethanol consumption promote insulin sensitivity and leanness by
      stimulating AMP-activated protein kinase?
AB  - There is good reason to believe that regular moderate alcohol consumption
      promotes insulin sensitivity of skeletal muscle; conceivably, this benefits the
      protective effects of moderate drinking on vascular health and risk for obesity
      and diabetes. The mechanism responsible for alcohol's insulin-sensitizing
      activity remains obscure. As a working hypothesis, it is proposed that metabolism
      of acetate in peripheral tissues generates sufficient levels of AMP to
      temporarily stimulate the AMP-activated protein kinase, which in turn induces the
      synthesis of certain long-lived proteins that act to boost insulin sensitivity
      and possibly aid the efficiency of fat oxidation as well.

PMID- 11516238
TI  - Endothelial cell apoptotic genes associated with the pathogenesis of thrombotic
      microangiopathies: an application of oligonucleotide genechip technology.
AB  - Idiopathic thrombotic thrombocytopenic purpura (TTP) is a disease characterized
      by the apoptotic injury of all microvascular endothelial cells (MVEC) except
      those of pulmonary origin. It notably also spares EC of large vessel origin. It
      is fatal unless treated with plasma exchange. The EC lineage restriction of the
      apoptotic lesions in vivo is reproduced in vitro following exposure of primary
      human MVEC derived from various tissues to TTP plasma. Oligonucleotide genechip
      technology was used to identify genes that may contribute to the resistance of
      lung MVEC to apoptosis induced by TTP plasma and to explore the intrinsic
      genotypic heterogeneity between MVEC of TTP-sensitive (skin) versus resistant
      (lung) lineage. Exposure of cells to TTP or normal plasma yielded 157 genes that
      were differentially expressed in primary human lung MVEC. A global change in
      expression of pro- and anti-apoptotic genes was seen, including increases in
      caspase 1, Fas, and Bcl-xl, already shown by experimental means to be involved in
      TTP pathogenesis. Additional differences suggest the importance of pathways
      related to the death receptor ligand TRAIL, as well as a role for disruption of
      EC-extracellular matrix interactions in the initiation of apoptosis. Maintenance
      of specific prosurvival signals at baseline may be a feature of lung MVEC
      resistance in TTP as suggested by higher expression than skin EC of the TRAIL
      antagonist, osteoprotegerin, and the vascular endothelial growth factors,
      VEGF/VPF and VEGF-C, and their receptors, VEGFR-2 (KDR) and VEGFR-3 (Flt4).

PMID- 11516239
TI  - Cyclic AMP and acidic fibroblast growth factor have opposing effects on tight and
      adherens junctions in microvascular endothelial cells in vitro.
AB  - Endothelial adherens junctions (AJ) and tight junctions (TJ) are important
      determinants of vascular permeability and cell morphology. Here, we investigate
      their regulation, in primary human placental microvascular endothelial cell
      (HPMEC) cultures, by either aFGF plus heparin (ECGS) or elevated cAMP. The
      proliferation of HPMEC was weakly stimulated by ECGS, while cAMP was inhibitory.
      ECGS had little effect on transendothelial resistance (TER), but increased
      macromolecular permeability, whereas cAMP induced a twofold increase in TER and
      reduced macromolecular permeability. Ultrastructurally, ECGS-treated HPMEC
      exhibited an "activated" phenotype typified by proliferating cells, with poorly
      organized cell-cell junctions, whereas cAMP-treated cells appeared quiescent and
      markedly flattened with extended paracellular junctions, resembling endothelium
      in situ. The expression and localization of junctional molecules, F-actin, and
      junctional phosphotyrosine were examined by confocal microscopy and
      immunoblotting. Junctional molecules in ECGS-treated cells were less organized at
      lateral membranes than in control cells, whereas in cAMP-treated cells, they were
      highly localized at continuous contacts. These differences correlated with the
      intensity of junctional phosphotyrosine, being lowest with cAMP treatment. In the
      AJ of ECGS-treated and control cells, beta-catenin predominated but in cAMP
      treated cells, gamma-catenin/plakoglobin was enriched. In addition, cAMP
      upregulated junctional expression of VE-cadherin and PECAM-1 and increased the
      levels of the TJ molecules occludin and ZO-1. The expression levels of junctional
      components, and their tyrosine phosphorylation, play an important role in dynamic
      regulation of endothelial cell-cell junctions.

PMID- 11516240
TI  - *NO and oxyradical metabolism in new cell lines of rat brain capillary
      endothelial cells forming the blood-brain barrier.
AB  - To investigate the relevance of *NO and oxyradicals in the blood-brain barrier
      (BBB), differentiated and well-proliferating brain capillary endothelial cells
      (BCEC) are required. Therefore, rat BCEC (rBCEC) were transfected with
      immortalizing genes. The resulting lines exhibited endothelial characteristics
      (factor VIII, angiotensin-converting enzyme, high prostacyclin/thromboxane
      release rates) and BBB markers (gamma-glutamyl transpeptidase, alkaline
      phosphatase). The control line rBCEC2 (mock transfected) revealed fibroblastoid
      morphology, less factor VIII, reduced gamma-glutamyl transpeptidase, weak radical
      defence, low prostanoid metabolism, and limited proliferation. Lines transfected
      with immortalizing genes (especially rBCEC4, polyoma virus large T antigen)
      conserved primary properties: epitheloid morphology, subcultivation with high
      proliferation rate under pure culture conditions, and powerful defence against
      reactive oxygen species (Mn-, Cu/Zn-superoxide dismutase, catalase, glutathione
      peroxidase, glutathione) effectively controlling radical metabolism. Only 100
      microM H2O2 overcame this defence and stimulated the formation of eicosanoids
      similarly as in primary cells. Some BBB markers were expressed to a lower degree;
      however, cocultivation with astrocytes intensified these markers (e.g., alkaline
      phosphatase) and paraendothelial tightness, indicating induction of BBB
      properties. Inducible NO synthase was induced by a cytokine plus
      lipopolysaccharide mixture in all lines and primary cells, resulting in *NO
      release. Comparing the cell lines obtained, rBCEC4 are stable immortalized and
      reveal the best conservation of properties from primary cells, including enzymes
      producing or decomposing reactive species. These cells can be subcultivated in
      large amounts and, hence, they are suitable to study the role of radical
      metabolism in the BBB and in the cerebral microvasculature.

PMID- 11516241
TI  - Effects of L-NA and sodium nitroprusside on ischemia/reperfusion-induced
      leukocyte adhesion and macromolecular leakage in hamster cheek pouch venules.
AB  - Our objective was to study how the topical application of a nitric oxide synthase
      inhibitor (l-NA, Nomega-nitro-L-arginine) and a nitric oxide donor, sodium
      nitroprusside (SNP), could modulate leukocyte adhesion (sticking) and
      microvascular permeability as altered by ischemia/reperfusion (I/R) and topically
      applied histamine after I/R. Golden hamsters were prepared for intravital
      microscopy. Ischemia was induced by an inflatable silicon rubber cuff mounted
      around the neck of the cheek pouch prepared for intravital microscopy. Saline, L
      NA, sodium nitroprusside, and histamine were applied in the superfusion solution.
      FITC-dextran was injected iv 30 min before initiation of ischemia as a marker of
      microvascular permeability. L-NA 10(-5) M inhibited both the increase in number
      of sticking leukocytes and the increase in vascular permeability after I/R
      compared with the untreated control group of hamsters. SNP neutralized this
      effect of L-NA on leukocytes and vascular permeability and caused arteriolar
      dilation at the concentration used, 10(-6) M. Both SNP and L-NA + SNP enhanced
      the I/R-induced macromolecular leakage. The topical application of SNP and SNP +
      L-NA did not modify the response to histamine after I/R compared with the
      untreated control group. In hamsters not subjected to I/R, histamine-induced
      macromolecular leakage was inhibited by L-NA and L-NA + SNP but was unchanged by
      SNP. It is concluded that inhibition of nitric oxide formation by L-NA reduced
      both leukocyte adhesion in postcapillary venules and the increase in
      macromolecular leakage and that a NO donor such as SNP could enhance the
      macromolecular leakage response to I/R.

PMID- 11516242
TI  - Activation of carrier-mediated transport of L-cystine at the blood-brain and
      blood-retinal barriers in vivo.

PMID- 11516243
TI  - Measurement of blood flow through the retinal circulation of the cat during
      normoxia and hypoxemia using fluorescent microspheres.
AB  - The most successful method for measuring absolute blood flow rate through the
      retinal circulation has been the use of radioactive microspheres. The purpose of
      this study was to develop a microsphere method that did not have the drawbacks
      associated with radioactivity and to use this method to make measurements of
      retinal blood flow in the cat. Blood flow measurements were made by injecting 15
      microm-diameter polystyrene microspheres into the left ventricle of anesthetized,
      artificially ventilated cats. These microspheres were labeled with one of three
      fluorescent dyes. Retinal blood flow measurements were made by determining the
      number of spheres that were embedded in the retina and comparing them to the
      number found in a reference sample. Spheres in the retina were counted by making
      retinal whole mounts and taking retinal images with a CCD camera mounted on an
      epifluorescence microscope equipped with filter sets appropriate for imaging the
      dyes used to label the spheres. Blood flow measurements made under normal
      conditions showed a mean retinal blood flow of 19.8 +/- 12.4 ml/min 100 g tissue
      (mean +/- SD; n = 15 cats). Since the retinal circulation perfuses only the inner
      half of the retina, the effective flow rate in that region is about twice this
      value. RBF increased during hypoxemia (P(a)O2 < 42 mm Hg) to 336% of the normoxic
      value on average. Analysis of sphere deposition patterns showed that the central
      retina had a higher blood flow than the peripheral retina, although this
      difference was significant only during hypoxemia. We conclude that even with a
      relatively small number of spheres deposited in the retina, the technique can
      reveal important properties of the retinal circulation.

PMID- 11516244
TI  - Primary cutaneous microangiopathy in heart recipients.
AB  - In this study we investigated whether a disturbance in microcirculation is
      detectable in heart recipients with cardiac allograft vasculopathy (CAV) and
      severe hypercholesterolemia (n = 11) and in 7 heart recipients without CAV in
      comparison to patients with severe coronary artery disease (n = 49) and age
      matched apparently healthy subjects (n = 100). For this purpose, the flow
      velocity of erythrocytes through cutaneous capillaries at the nail fold of the
      finger was measured under resting conditions. In addition, reactive hyperemia in
      the same capillaries after a 3-min ischemia was determined. Patients with CAV and
      severe lipid disorder showed a pathological reduction in mean capillary
      erythrocyte velocity under resting conditions with v(RBC) = 0.10 +/- 0.07 mm/s.
      The latter was significantly and relevantly lower than in patients with coronary
      three-vessel disease (v(RBC) = 0.46 +/- 0.35 mm/s). It was notable that under
      resting conditions temporary cessation of flow occurred in 8 of the 11 patients
      which did not occur in healthy subjects and rarely in patients with three-vessel
      disease (1 of 49 patients). In comparison to age-matched healthy subjects (v(max)
      = 1.46 +/- 0.52 mm/s), the patients with three-vessel disease showed a
      significant reduction in postischemic maximum erythrocyte velocity (v(max) = 0.85
      +/- 0.55 mm/s), with a considerable shortening of the duration of reactive
      hyperemia. Patients with CAV demonstrated a total loss of postischemic reactive
      hyperemia (only 1 of the 11 patients presented a weak reactive hyperemia). Since
      no macroangiopathy was detectable in the upstream arm arteries, primary cutaneous
      microangiopathy can be assumed in patients with cardiac allograft vasculopathy
      and severe hypercholesterolemia.

PMID- 11516245
TI  - Activation of rho is involved in the mechanism of hydrogen-peroxide-induced lung
      edema in isolated perfused rabbit lung.
AB  - Acute lung injury is attributed primarily to increased vascular permeability
      caused by reactive oxygen species derived from neutrophils, such as hydrogen
      peroxide (H2O2). Increased permeability is accompanied by the contraction and
      cytoskeleton reorganization of endothelial cells, resulting in intercellular gap
      formation. The Rho family of Ras-like GTPases is implicated in the regulation of
      the cytoskeleton and cell contraction. We examined the role of Rho in H2O2
      induced pulmonary edema with the use of isolated perfused rabbit lungs. To our
      knowledge, this is the first study to examine the role of Rho in increased
      vascular permeability induced by H2O2 in perfused lungs. Vascular permeability
      was evaluated on the basis of the capillary filtration coefficient (Kfc,
      ml/min/cm H2O/100 g). We found that H2O2 (300 microM) increased lung weight, Kfc,
      and pulmonary capillary pressure. These effects of H2O2 were abolished by
      treatment with Y-27632 (50 microM), an inhibitor of the Rho effector p160 ROCK.
      In contrast, the muscular relaxant papaverine inhibited the H2O2-induced rise in
      pulmonary capillary pressure, but did not suppress the increases in lung weight
      and Kfc. These findings indicate that H2O2 causes pulmonary edema by elevating
      hydrostatic pressure and increasing vascular permeability. Y-27632 inhibited the
      formation of pulmonary edema by blocking both of these H2O2-induced effects. Our
      results suggest that Rho-related pathways have a part in the mechanism of H2O2
      induced pulmonary edema.

PMID- 11516246
TI  - Differences in cortical microcirculation in the kidneys of unilaterally
      congenital hydronephrotic rats.
AB  - The surgically induced split hydronephrotic kidney has been generally accepted as
      a valid model for the assessment of renal microcirculation by means of intravital
      microscopy. Whereas nearly all previous work on this issue has been done with a
      transillumination technique, we used an epiillumination model that is suitable
      for investigation of microvascular perfusion in both normal and hydronephrotic
      kidneys without surgical manipulation of the ureter. By means of the congenital
      unilaterally hydronephrotic Tauchi rat, microcirculation of the hydronephrotic
      and that of the nonhydronephrotic kidney were compared. For that purpose both the
      hydronephrotic and the nonhydronephrotic kidneys of Tauchi rats were exteriorized
      on a specially designed microscopy stage. After injection of FITC-dextran and
      rhodamine 6G, microvascular perfusion was assessed in both kidneys. The new model
      allowed visualization of arterioles, capillaries, and postcapillary venules in
      both the hydronephrotic and the nonhydronephrotic kidneys. Glomeruli could only
      be regularly seen in the hydronephrotic kidney, but also in some normal kidneys.
      Capillary blood cell velocity was significantly higher in the hydronephrotic
      kidneys (0.67 +/- 0.03 mm/s) compared to the normal kidney (0.32 +/- 0.05 mm/s; P
      < 0.05), whereas capillary diameters were smaller (4.2 +/- 0.02 microm vs. 5.7 +/
      0.2 microm; P < 0.05). In addition, the hydronephrotic kidney showed a
      significantly lower density of perfused microvessels compared to the normal
      controls. Epiillumination intravital microscopy allows assessment of the cortical
      microcirculation in both the hydronephrotic and the nonhydronephrotic kidneys
      without surgical induction of hydronephrosis. The hydronephrotic kidney shows
      significant microcirculatory differences compared to normal kidneys that should
      be taken into account when using a hydronephrotic model for pharmacological
      testing.

PMID- 11516247
TI  - Direct measurement of VEGF-induced nitric oxide production by choroidal
      endothelial cells.
AB  - Vascular endothelial growth factor (VEGF) and nitric oxide (NO) seem to be
      involved in the process of angiogenesis, but their interactions are not clearly
      understood. The aim of this study was to investigate the influence of VEGF on NO
      production of choroidal endothelial cells (CEC) and its importance in
      angiogenesis. Experiments were performed using cultured bovine CEC. Basal NO
      release of unstimulated CEC was measured and compared to NO release of VEGF
      stimulated CEC (1, 10, and 100 ng/ml). Further, cells were pretreated with
      N(omega)-nitro-L-arginine methyl ester (L-NAME, 1 and 2 mM) and incubated with
      and without VEGF (10 ng/ml) to investigate the effect of blocking NO synthase. NO
      release into the medium was assessed by an amperometric NO sensor. To show the
      importance of NO in angiogenesis, proliferation and migration of CEC were
      measured after VEGF stimulation and in the presence or absence of L-NAME (1 and 2
      mM). Unstimulated CEC continuously produced low levels of NO. Stimulation of the
      cells with VEGF resulted in a dose-dependent increase in NO release. The time
      course after stimulation with 10 ng/ml VEGF was characterized by a prompt initial
      rise up to 140% of unstimulated levels and a subsequent sustained increase over
      120 min. Pretreatment with L-NAME attenuated the VEGF-induced response. L-NAME
      incubation alone led to a reduction in basal NO release. L-NAME also
      significantly diminished the VEGF-enhanced CEC proliferation and migration. The
      results demonstrate that VEGF enhances the formation of NO in cultured CEC. The
      blockade of NO production reduces CEC proliferation and migration, an effect
      which may be important for controlling angiogenesis, especially in reducing
      neovascularization in age-related macular degeneration in the eye.

PMID- 11516248
TI  - Arteriolar resistance and hemorheological disorders related to Raynaud's
      phenomenon.
AB  - The functional condition of resistance arteries in human hands was monitored with
      a noninvasive test. Blood flow velocity changes (Doppler flow meter) were
      monitored in the radial artery before and after a 1-min stop flow in the hand
      under conditions of stable systemic arterial pressure. In addition, the most
      significant parameter of hemorheological disorders in microcirculation, RBC
      aggregability, was investigated in the same patients' blood samples. The muscular
      tone of the resistance arteries was found to be a mean of 35% higher during
      Raynaud's phenomenon than in the healthy controls tested. The raised vascular
      tone was not related to the patients' age and had a pronounced tendency to rise
      with disease duration. RBC aggregability was a mean of 4% higher in the patients
      than in the healthy controls, and the difference was not reliable. We concluded
      that, among principal pathogenic factors which might cause deficiency of the
      blood supply to fingers, it is the enhanced tone of resistance arteries that is
      primarily responsible for the development of Raynaud's phenomenon, while
      hemorheological disorders are not, or are considerably less, involved in the
      development of the principal symptom of the disease, deficient blood supply to
      the fingers.

PMID- 11516249
TI  - Nitric oxide/cGMP-induced inhibition of calcium and chloride currents in retinal
      pericytes.
AB  - In the CNS, contractile pericytes positioned on endothelium-lined lumens appear
      to play a role in regulating capillary blood flow. This function may be
      particularly important in the retina where pericytes are more numerous than in
      other tissues. Despite the importance of pericytes, knowledge of the effects of
      vasoactive molecules, such as nitric oxide (NO), on the physiology of these cells
      is limited. Since it is likely that ion channels play a role in the response of
      pericytes to signaling molecules from other cells, we used the perforated-patch
      configuration of the patch-clamp technique to record the whole-cell currents of
      pericytes located on microvessels freshly isolated from the rat retina. We found
      that voltage-gated calcium currents and calcium-activated chloride currents were
      inhibited during exposure to the NO donor, sodium nitroprusside (SNP). 8-Bromo
      cyclic guanosine monophosphate (cGMP) mimicked these effects. In contrast,
      neither SNP nor the cGMP analog significantly affected the potassium or
      nonspecific cation conductances, which establish the resting membrane potential
      of retinal pericytes. Consistent with endogenous NO suppressing pericyte channel
      activity, exposure of isolated microvessels to an inhibitor of NO synthase
      increased the calcium and chloride currents. Since our experiments indicate that
      chloride channel activity is dependent, in part, upon the function of voltage
      gated calcium channels, we postulate that a NO/cGMP-mediated inhibition of
      calcium channels reduces calcium influx and, thereby, lessens the opening of the
      calcium-activated chloride channels. This may be one mechanism by which NO
      decreases the contractile tone of pericytes.

PMID- 11516250
TI  - Upregulation of MHC class I molecules on human dermal microvascular endothelial
      cells by interferon alpha.

PMID- 11516251
TI  - Inspiratory-induced vasoconstrictive episodes in healthy skin described by
      simultaneous measurement of blood flow and oxygen saturation.

PMID- 11516253
TI  - Apoptosis in atherosclerosis: pathological and pharmacological implications.
AB  - Normal embryonic development, tissue differentiation and repair in the eukaryote
      requires a tightly regulated apoptosis, or programmed cell death. Apoptosis also
      plays an essential role in different pathological processes including
      atherosclerosis, in which it affects all cell types in the atherosclerotic
      lesion, including endothelial cells, vascular smooth muscle cells, and
      macrophages. During atherosclerosis progression, pro- and anti-apoptotic signals
      abound in the evolving lesion. Apoptosis limits the number of a particular cell
      type that accumulates in the lesion and slows down the overall progression of the
      lesion. On the other hand, it contributes to the production of unstable plaques.
      Many pharmacological agents used to treat cardiovascular and lipid disorders have
      pro- or/and anti-apoptotic effects. Pharmaceuticals that modulate apoptosis in
      specific types of cell can potentially serve as anti-atherogenic agents. However,
      to develop agents for clinical use requires a thorough knowledge of the
      pathophysiology of apoptosis in atheromatous lesions, a highly cell-specific
      process. Here we review our current understanding of the process to provide a
      background for future pharmacological research in the area.

PMID- 11516252
TI  - Microvascularization and ventricular function after local alginate-encapsulated
      angiogenic growth factor treatment in a rat cryothermia-induced myocardial
      infarction model.

PMID- 11516254
TI  - Evaluation of chronic exposure of the male rat reproductive system to the
      insecticide methomyl.
AB  - Carbamate insecticides are widely used in industry, agriculture and for public
      health purposes. Numerous incidents of acute carbamate poisoning have resulted
      from inhalation of sprays or contamination of crops or food. This work was
      conducted to study the effect of chronic exposure to methomyl on hormonal,
      histopathological and histochemical changes in rat testes. The treated group
      received methomyl orally (17 mg kg(-1)in saline) daily for 2 months, while the
      control group received saline. A significant decrease in the level of
      testosterone was observed in the intoxicated animals, while the levels of FSH, LH
      and prolactin were significantly increased. Histopathological studies of the
      intoxicated rat testes revealed variable degrees of degenerative changes in the
      seminiferous tubules up to total cellular destruction. As regards the
      histochemical results, it was found that both acid phosphatase and alpha esterase
      enzyme activity was significantly increased compared to the control group. On the
      other hand succinic dehydrogenase enzyme activity was significantly reduced. No
      significant change was observed in alkaline phosphatase enzyme activity. The
      hormonal changes and testicular damage continued for 30 days after withdrawal of
      the insecticide indicating a persistent effect. From the above-mentioned
      findings, it has been concluded that chronic exposure to methomyl insecticide has
      deleterious effects on rat testes. Therefore application of such insecticide
      should be limited to a designed program with special care in handling to limit or
      minimize its hazards.

PMID- 11516255
TI  - Toxicity of theophylline depends on plasma concentration by single and also
      repeated dosing in rats.
AB  - The purpose of this study was to evaluate the relationship between the in vivo
      toxicity and plasma concentration of theophylline. Theophylline was administered
      intravenously in single doses ( 50, 100, 150 and 200 mg kg(-1)once a day) or
      repeated doses (12.5, 25 and 90 mg kg(-1)/day for 28 days) in rats. Plasma
      concentrations of theophylline increased dose-dependently in both single and
      repeated doses, and there were no differences due to effects of 28-times repeated
      administration. Neither single dose at 50 mg kg(-1)nor repeated dose at 12.5 mg
      kg(-1)/day injections of theophylline showed toxic signs, in which plasma
      concentrations of theophylline were less than 110 and 22.5 microg ml(-1),
      respectively. Theophylline induced myocardial fibrosis in 25 mg kg(-1)/day and
      more treated groups: in which plasma concentrations of theophylline were more
      than 50 microg ml(-1). At doses of 100 mg kg(-1)(single) and 90 mg kg(-1)/day
      (repeated), theophylline caused tachypnea and excitement of movement. Each
      theophylline concentration in plasma was more than 194 microg ml(-1)in single 100
      mg kg(-1)and 162 microg ml(-1)in repeated 90 mg kg(-1)/day injections,
      respectively. Death was observed at a dose of 200 mg kg(-1), in which the plasma
      concentration of theophylline was more than 264 microg ml(-1). Moreover, the
      recovery period from signs of toxic poisoning to normality in the 200 mg kg(
      1)treated group was greater than that in the 150 mg kg(-1)and less treated
      groups. The results indicated that the in vivo toxicity of theophylline is highly
      dependent on plasma concentrations in rats which received single and also
      repeated doses of theophylline.

PMID- 11516256
TI  - The effects of acute melatonin and ethanol treatment on antioxidant enzyme
      activities in rat testes.
AB  - The pineal hormone melatonin (N -acetyl, 5-methoxytryptamine) was recently
      accepted to act as an antioxidant under both in vivo and in vitro conditions. In
      this study, we examined the possible preventive effect of melatonin on ethanol
      induced lipid peroxidation in rat testes. Thirty-seven male Wistar albino rats,
      5.5--6 months old, were randomly divided into four groups (9--10 animals in
      each). The first group (control animals) received 4% ethanol at similar intervals
      to the experimental groups to equalize the stress effect. The second group
      received only melatonin i.p. 7 mg kg(-1)bw three times over 1.5 h intervals. The
      third group received only 30% alcohol 3 g kg(-1)bw twice daily. The fourth group
      were treated with melatonin and ethanol according to the above protocol,
      melatonin injections preceding ethanol treatments. The product of lipid
      peroxidation, malondialdehyde (MDA) and antioxidant enzymes, superoxide dismutase
      (Cu--Zn SOD), glutathione peroxidase (GPx) and catalase (CAT) were measured in
      the post-mitochondrial fraction of the testes. MDA levels were significantly
      increased due to acute ethanol intoxication. GPx activity was higher in the three
      experimental groups than the control levels. The activity of CAT was increased
      significantly in the melatonin plus ethanol-treated group but the other groups
      appeared not to be influenced by acute ethanol treatment. Cu--Zn SOD activity
      remained unaltered. These results suggest that antioxidants may be a protective
      agent for the testicular injury caused by ethanol consumption.

PMID- 11516257
TI  - The effect of aminoguanidine on diabetes-induced inactivation of kidney
      Na(+),K(+)- ATPase in rats.
AB  - We studied the effect of aminoguanidine (AG), an inhibitor of advanced glycation
      product formation, on diabetes-induced oxidative damage. Renal cortex Na(+),K(+)-
      ATPase was chosen for study as a potential cellular target of oxygen radicals. In
      this study, the enzyme activity was reduced while malondialdehyde (MDA) and
      carbonyl levels were enhanced but sulphydryl (SH) level remained unchanged in the
      renal cortex in diabetic animals. Treatment of diabetic rats with AG had no
      significant effect on diabetes-induced impairments of enzyme activity and MDA but
      the carbonyl level readjusted to control level in the kidney. These results show
      that AG treatment at that dose did not exhibit profound antioxidant properties
      even if carbonyl stress was ameliorated by this treatment.

PMID- 11516258
TI  - Inhibition of mitochondrial carnitine palmitoyltransferase-1 by a trimetazidine
      derivative, S-15176.
AB  - The purpose of this study was to investigate the possible effect of the
      trimetazidine derivative S-15176 on carnitine palmitoyltransferase1 (CPT-1)
      activity in rat heart and liver mitochondria. S-15176 was compared with the other
      antianginal agents amiodarone, perhexiline and trimetazidine, which do not show
      any hemodynamic effects and which are believed to exert their effects by
      switching the cellular metabolism towards glucose utilization at the expense of
      lipid metabolism, increasing the yield of oxygen utilization. S-15176 inhibited
      CPT-1 in vitro and was more effective in heart (IC(50)= 16.8 micro M) than in
      liver ( 50.8 +/- 3.0 micro M). In the heart, its was less effective than the
      physiological inhibitor malonyl-CoA (IC(50)= 2.1 micro M), but it was more potent
      than amiodarone (IC(50)= 140 micro M). Kinetic experiments demonstrated a non
      competitive inhibition of CPT-1 by S-15176 indicating that the two compounds did
      not share the same site of action. CPT-1 inhibition was also obvious ex vivo, in
      heart and liver tissues, after a 2 week treatment with S-15176. This inhibitory
      effect may shift heart and liver metabolism from fatty acid to glucose oxidation
      and contribute to the anti-ischemic effects of the drug.

PMID- 11516259
TI  - Influence of capsaicin cream in rats with peripheral neuropathy.
AB  - We investigated the effect of topical application of capsaicin cream on
      withdrawal latency in the hind foot of rat in response to radiant heat in an
      experimental model of neuropathic pain. A neuropathic state was induced by loose
      ligation of the sciatic nerve with chromic gut suture. A marked thermal
      hyperalgesia was observed in response to heat stimulus applied to the operated
      side from 3 days through 2 weeks, followed by a gradual return to the control
      level by 35 days after surgery. Capsaicin cream applied to both the bilateral
      hind instep and sole once a day for a continuous period of 2 weeks or 4 weeks
      alleviated thermal hyperalgesia in a dose-dependent manner. A remarkable effect
      was observed 2 weeks after the start of the application and this effect proved to
      be reversible. On the other hand, in sham-operated animals when capsaicin cream
      was applied once daily from day 7 after the sham operation, from 1 day through 3
      weeks following capsaicin application, withdrawal latency of the sham-operated
      paws of the capsaicin-treated group was significantly increased as compared to
      that of the vehicle cream-treated group. The effects of antagonists of glutamate
      receptor and tachykinin receptors were investigated 7 days post surgery.
      Pretreatment with MK-801 (0.5 mg kg(-1), i.p.), but not with CNQX (0.5 mg kg(-1),
      i.p.), reversed the thermal hyperalgesia following nerve injury. Neither of
      RP67580 (1--10 mg kg(-1), i.p.) nor SR48968 (1--10 mg kg(-1), i.p.) had any
      effect on the withdrawal latency in the injured and non-injured hind paw. These
      results suggest that although the manifestation of effectiveness may be delayed
      by changes in networks of neurotransmitters related to the nociceptive pathways
      following nerve injury, longer-term repetitive application of capsaicin cream has
      a significant therapeutic effect on subjects with painful peripheral neuropathy.

PMID- 11516260
TI  - Selectivity of blocking of low- versus high-voltage activated calcium currents by
      the dihydropyridine derivatives Bay E5759 and Bay A4339 in neuroblastoma--glioma
      NG 108-15 cells.
AB  - Beneficial therapeutic effects of dihydropyridine derivatives in cardiovascular
      and neurological disorders are often associated with selective L-type
      Ca(2+)channel blockade. Here the new dihydropyridine derivatives Bay E5759 (1,4
      dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic acid ethyl-1
      methylethyl ester) and Bay A4339 (1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5
      pyridinedicarboxylic acid dimethyl-ester) were tested for their potency and
      selectivity of blocking of Ba(2+)currents mediated by low-(LVACC)vs high-voltage
      activated Ca(2+)channels (HVACC) in neuroblastoma-glioma hybrid cells.
      Nisoldipine and mibefradil served as reference compounds. Bay E5759 and Bay A4339
      blocked HVACC at low nanomolar concentrations, whereas LVACC was hardly reduced
      at up to 10 microM. The order of potency for blockade of HVACC was Bay E5759
      (IC(50): 0.4 nM) > Bay A4339 (2.5 nM) approximately = nisoldipine (4 nM) >>
      mibefradil (3.8 microM). Thus Bay E5759 and Bay A4339 are highly potent and
      selective blockers of HVACC, presumably L-type Ca(2+)channels.

PMID- 11516261
TI  - Differences in the behaviour of Sprague--Dawley and Lewis rats during repeated
      passive avoidance procedure: effect of amphetamine.
AB  - The present paper investigated the differences in passive avoidance learning
      between Sprague--Dawley and Lewis rats. After initial habituation (experimental
      Part 1), measured as latencies to enter the dark, preferable compartment, the
      effect of treatment with amphetamine (8 mg kg(-1)b.w.), the retention performance
      compared with controls (saline) was tested in both rat strains in Parts 2--4. The
      intervals between Parts 2--4 were 24 or 49 days. Each experimental part consisted
      of testing lasting 6 days. On the 7th day the rats received drug treatment 1 h
      before the application of foot shock. The differences between rat strains were
      already detectable at the beginning of the study. During the repeated exposures
      of rats in Part 1, only Lewis rats, in contrast to Sprague--Dawley rats,
      exhibited the habituation. The repeated testing of rats in Parts 2--4, due to
      previous experience with an aversive stimulus, was considered as the retention
      test. In Parts 2--3 we observed only minor differences in the responses of both
      rat strains tested. Also no significant differences were observed between rat
      strains after amphetamine treatment that induced an amnesia-like effect in all
      retention trials. However, data shown in Part 4 revealed the largest differences
      between both strains. Control Lewis rats exhibited significantly higher retention
      responses than Sprague--Dawley rats. In the latter strain we observed no
      differences in avoidance latencies between controls and amphetamine treated rats.
      In Lewis rats the difference in avoidance performance between controls and
      amphetamine treated animals was highly significant due to their enhanced
      retention performance. In conclusion, the results presented in this study extend
      the known behavioural differences in tested rat strains to the passive avoidance
      procedure that, in addition, was performed for a total period of 4 months. Due to
      a known deficiency of hypothalamo-pituitary-adrenal axis activity in Lewis rats
      it can be hypothesized that the behavioural dissociation of this strain from
      Sprague--Dawley rats could be related to the different activity of this
      regulatory axis in the rat strains tested.

PMID- 11516262
TI  - Captopril and its time of administration in myocardial ischaemic-reperfusion
      injury.
AB  - The present study was designed to investigate the role of captopril in an in vivo
      model of myocardial ischaemic-reperfusion injury with respect to its time of
      administration. In open-chest pentobarbitone anaesthetized cats, the left
      anterior descending coronary artery was occluded for 15 min followed by 60 min of
      reperfusion. Vehicle (saline) or captopril (4 mg kg(-1)) was administered 10 min
      before instituting ischaemia (pre-treatment) or 5 min before reperfusion (post
      treatment). In the vehicle-treated group, ischaemic-reperfusion injury (IRI) was
      evidenced by enhanced plasma renin activity, depression of global haemodynamic
      function (mean arterial pressure, left ventricular-end-diastolic-pressure, peak
      positive and negative dP/dt) along with depletion of myocardial high energy
      phosphate (HEP) compounds. Oxidant stress in IRI was evidenced by raised levels
      of myocardial thiobarbituric acid reactive substances (TBARS) and depletion of
      endogenous myocardial antioxidants (glutathione, superoxide dismutase and
      catalase). Pre-treatment with captopril prevented (i) loss of myocardial
      haemodynamic function, (ii) rise in TBARS and (iii) depletion of myocardial HEP
      compounds. However, in the post-treatment group, only partial recovery of
      myocardial haemodynamic function, with no significant reduction in TBARS, was
      observed. Glutathione, superoxide dismutase and catalase were unaffected by
      either treatment schedules. The results of the present study suggest that
      captopril is more effective in attenuating ischaemic-reperfusion injury when
      administered before ischaemia rather than before reperfusion.

PMID- 11516263
TI  - Norepinephrine prevents the adverse effects of lidocaine upon the heart. An
      experimental study in isolated guinea-pig hearts.
AB  - The adverse effects of local anesthetics associated with catecholamines upon the
      cardiovascular system, such as arterial pressure alterations and cardiac
      arrhythmias, have been highly discussed in pharmacological literature. When
      present in the blood circulation, the anesthetic salt promotes depressing effects
      at the cardiovascular system level, whilst the catecholaminic vasoconstrictors
      promote opposite effects upon the cardiovascular system. This paper aimed to
      verify which component is responsible for the initial effect upon the isolated
      heart of the guinea-pig by comparing the same anesthetic with and without
      vasoconstrictor. Guinea-pig hearts perfused using the Langendorff method received
      separate injections of lidocaine hydrochloride, without vasoconstrictor (LC), and
      with the vasoconstrictor norepinephrine at 1 : 50,000 (LCN) in doses of 3, 4 and
      5 mg. LC was seen to significantly reduce the contraction force (CF) and the
      cardiac rate (CR) at all injected doses and at all times registered. LCN, though,
      significantly reduced CF in all doses only at 15 s after administration. At 30
      and 60 s, LCN elevated CF to values close to those of the control. LCN in its 3
      mg dose significantly increased CR at 30 and 60 s; with the 4 mg dose,
      significant alterations did not occur in CR and with the 5 mg dose CR was reduced
      significantly at 15 and 30 s, returning to values close to those of the control
      at 60 s. The electrocardiographic traces with LCN were similar to those with LC
      with a reduction occurring in the automatism of the sinus node, prolongation of
      the PR interval and widening of QRS, with all doses utilized at 15 s. Soon after
      the administration of LC and LCN ventricular asystole occurred, having a larger
      duration with LC. This duration was also increased when higher doses of
      anesthetics were used. The authors concluded that the initial cardio-depression
      effect of local anesthetics, with the vasoconstrictor norepinephrine, in the
      isolated guinea-pig heart is due to the anesthetic salt and that the
      vasoconstrictor exerts a protecting action against this effect.

PMID- 11516264
TI  - Astilbin selectively facilitates the apoptosis of interleukin-2-dependent
      phytohemagglutinin-activated Jurkat cells.
AB  - The present study examined the relationship between the activation of T cells and
      the apoptosis-facilitating effect of astilbin on them. By the stimulation of PHA,
      a remarkable IL-2 production was detected in the supernatant of Jurkat cells
      after 120 h among 72--144 h incubation. This kinetics was quite in accordance
      with that of astilbin-induced apoptosis of Jurkat cells, where 1 h-exposure of
      the PHA-activated cells to astilbin caused a significantly increased apoptosis in
      a dose-dependent manner. To the Jurkat cells that had been cultivated for 72--144
      h without PHA, however, astilbin did not show any facilitation of the cell
      apoptosis. Pre-treatment by cyclosporine A simultaneously with PHA dose
      dependently lowered the IL-2 production and susceptibility of the cells to
      astilbin, while the treatment after 120 h of PHA-activation did not. The
      exogenous IL-2 treatment after 72 h of PHA-activation significantly and dose
      dependently raised the susceptibility of the Jurkat cells to astilbin. These
      results indicated the dependency of the apoptosis-facilitating effect of astilbin
      on appropriate status of activated T lymphocytes with a relation to IL-2
      production. This characteristic of astilbin may be of great significance for the
      treatment of a variety of immunologically related diseases.

PMID- 11516265
TI  - Effects of mepartricin on estradiol and testosterone serum levels and on
      prostatic estrogen, androgen and adrenergic receptor concentrations in adult
      rats.
AB  - The effects induced by oral administration of 0, 5 and 20 mg of meparticin kg(
      1)of body weight for 28 days (group 1, 2 and 3, respectively) upon prostatic
      estrogen, androgen, alpha(1)- and beta-adrenergic receptor concentrations and on
      estradiol and testosterone serum levels in adult male rats were studied. The
      effects produced by mepartricin treatments on the weight and dimension of the
      gland were investigated. Both mepartricin dosages induced significant decreases
      (P< 0.05) of the absolute and relative weights and of the dimensions of the
      prostate. A significant dose-dependent decrease (P< 0.05) in estradiol serum
      levels was observed in treated rats, whereas no significant modifications were
      found in testosterone serum levels. As far as prostatic steroid receptor
      concentrations were concerned, a significant (P< 0.05) decrease in estrogen
      receptor number was observed in both treated groups, whilst a significant
      increase (P< 0.05) of androgen receptor concentrations was recorded only in rats
      treated with 20 mg mepartricin kg(-1). Conversely, a dose-dependent up-regulation
      of both prostatic alpha(1)- and beta-AR was found. Data obtained suggest that the
      prostatic alpha(1)-AR expression may be strongly influenced by estrogen
      deprivation (mepartricin treatment), therefore the combination of estrogen
      suppression (mepartricin) and adrenergic suppression (alpha(1)-AR blockers) may
      be suggested as a possible pharmacotherapeutic strategy for the treatment of
      benign prostatic hyperplasia.

PMID- 11516267
TI  - Tetrahedral onsager crosses for solubility improvement and crystallization
      bypass.
AB  - Pure organic molecules exhibiting a suitable concave rigid shape are expected to
      give porous glasses in the solid state. Such a feature opens new opportunities to
      avoid crystallization and to improve molecular solubility in relation to the high
      internal energy of these solid phases. To quantitatively explore the latter
      strategy, a series of rigid tetrahedral conjugated molecules nC and the
      corresponding models nR have been synthesized. Related to the present purpose,
      several properties have been investigated using UV absorption, steady-state
      fluorescence emission, differential scanning calorimetry, (1)H NMR translational
      self-diffusion, magic angle spinning (13)C NMR, and multiple-beam interferometry
      experiments. The present tetrahedral crosses are up to 8 orders of magnitude more
      soluble than the corresponding model compounds after normalization to the same
      molecular length. In addition, they give concentrated monomeric solutions that
      can be used to cover surfaces with homogeneous films whose thickness goes down to
      the nanometer range. Such attractive features make cross-like molecular
      architectures promising for many applications.

PMID- 11516266
TI  - Acid/azole complexes as highly effective promoters in the synthesis of DNA and
      RNA oligomers via the phosphoramidite method.
AB  - The utility of various kinds of acid salts of azole derivatives as promoters for
      the condensation of a nucleoside phosphoramidite and a nucleoside is
      investigated. Among the salts, N-(phenyl)imidazolium triflate, N-(p
      acetylphenyl)imidazolium triflate, N-(methyl)benzimidazolium triflate,
      benzimidazolium triflate, and N-(phenyl)imidazolium perchlorate have shown
      extremely high reactivity in a liquid phase. These reagents serve as powerful
      activators of deoxyribonucleoside 3'-(allyl N,N-diisopropylphosphoramidite)s or
      3'-(2-cyanoethyl N,N-diisopropylphosphoramidite)s employed in the preparation of
      deoxyribonucleotides, and 3'-O-(tert-butyldimethylsilyl)ribonucleoside 2'-(N,N
      diisopropylphosphoramidite)s or 2'-O-(tert-butyldimethylsilyl)ribonucleoside 3'
      (N,N-diisopropylphosphoramidite)s used for the formation of 2'-5' and 3'-5'
      internucleotide linkages between ribonucleosides, respectively. The azolium salt
      has allowed smooth and high-yield condensation of the nucleoside phosphoramidite
      and a 5'-O-free nucleoside, in which equimolar amounts of the reactants and the
      promoter are employed in the presence of powdery molecular sieves 3A in
      acetonitrile. It has been shown that some azolium salts serve as excellent
      promoters in the solid-phase synthesis of oligodeoxyribonucleotides and
      oligoribonucleotides. For example, benzimidazolium triflate and N
      (phenyl)imidazolium triflate can be used as effective promoters in the synthesis
      of an oligodeoxyribonucleotide, (5')CGACACCCAATTCTGAAAAT(3') (20mer), via a
      method using O-allyl/N-allyloxycarbonyl-protected deoxyribonucleoside 3'
      phosphoramidites or O-(2-cyanoethyl)/N-phenoxyacetyl-protected
      deoxyribonucleotide 3'-phosphoramidite as building blocks, respectively, on high
      cross-linked polystyrene resins. Further, N-(phenyl)imidazolium triflate is
      useful for the solid-phase synthesis of oligoribonucleotides, such as
      (5')AGCUACGUGACUACUACUUU(3') (20mer), according to an allyl/allyloxycarbonyl
      protected strategy. The utility of the azolium promoter has been also
      demonstrated in the liquid-phase synthesis of some biologically important
      substances, such as cytidine-5'-monophosphono-N-acetylneuraminic acid (CMP
      Neu5Ac) and adenylyl(2'-5')adenylyl(2'-5')adenosine (2-5A core).

PMID- 11516268
TI  - Cyclic homooligomers from sugar amino acids: synthesis, conformational analysis,
      and significance.
AB  - Sugar amino acids (SAAs) were designed as new building blocks carrying an amino
      group and a carboxyl group on a carbohydrate scaffold. By exploiting standard
      solid- and solution-phase coupling procedures, linear and cyclic homooligomers
      containing glucosyluronic acid methylamine (Gum) were synthesized. We achieved a
      high yield and a very short coupling time for the oligomerization and cyclization
      of sequences encompassing two, three, four, and six Gum units. The synthesis of
      cyclic oligomers containing only SAAs as repetitive units has not been reported
      before. The conformational preferences in aqueous solution of the cyclic
      derivatives and their applications as potential host molecules are described
      herein. Benzoic acid and p-nitrophenol were chosen as model guest molecules to
      study the formation of cyclodextrin-like inclusion complexes. The complexation
      behavior of the cyclic hexamer was proved from three different points of view:
      chemical shifts, longitudinal relaxations (T(1)), and diffusion coefficients. All
      of them showed different values for host and guest molecules measured
      independently and in the presence of each other.

PMID- 11516269
TI  - Interfacial phase transition of an environmentally responsive elastin biopolymer
      adsorbed on functionalized gold nanoparticles studied by colloidal surface
      plasmon resonance.
AB  - The change in optical properties of colloidal gold upon aggregation has been used
      to develop an experimentally convenient colorimetric method to study the
      interfacial phase transition of an elastin-like polypeptide (ELP), a thermally
      responsive biopolymer. Gold nanoparticles, functionalized with a self-assembled
      monolayer (SAM) of mercaptoundecanoic acid onto which an ELP was adsorbed,
      exhibit a characteristic red color due to the surface plasmon resonance (SPR) of
      individual colloids. Raising the solution temperature from 10 degrees C to 40
      degrees C thermally triggered the hydrophilic-to-hydrophobic phase transition of
      the adsorbed ELP resulting in formation of large aggregates due to interparticle
      hydrophobic interaction. Formation of large aggregates caused a change in color
      of the colloidal suspension from red to violet due to coupling of surface
      plasmons in aggregated colloids. The surface phase transition of the ELP was
      reversible, as seen from the reversible change in color upon cooling the
      suspension to 10 degrees C. The formation of colloidal aggregates due to the
      interfacial phase transition of adsorbed ELP was independently verified by
      dynamic light scattering of ELP-modified gold colloids as a function of
      temperature. Colloidal SPR provides a simple and convenient colorimetric method
      to study the influence of the solution environment, interfacial properties, and
      grafting method on the transition properties of ELPs and other environmentally
      responsive polymers at the solid-water interface.

PMID- 11516270
TI  - Interfacial nonradiative energy transfer in responsive core-shell hydrogel
      nanoparticles.
AB  - Fluorescently labeled core-shell latex particles composed mainly of the
      thermoresponsive polymer poly-N-isopropylacrylamide (p-NIPAm) have been
      synthesized such that an energy transfer donor (phenanthrene) and an energy
      transfer acceptor (anthracene) are covalently localized in the core and shell,
      respectively. When the thermally induced particle deswelling is interrogated by
      photon correlation spectroscopy (PCS), a continuous (non-first order) phase
      transition is observed. Conversely, when the nonradiative energy transfer (NRET)
      efficiency is used to probe the collapse of these same particles, the phase
      transition event is observed to occur over a much smaller temperature range and
      approaches first-order (discontinuous) behavior. Furthermore, core-shell
      particles with differing shell thicknesses display identical phase transition
      temperatures when PCS is used to monitor the transition, while NRET measurements
      show a clear increase in collapse temperature as the shell thickness is
      increased. These apparently contradictory results are discussed in terms of a
      radial phase coexistence that exists in the microgel particles, which arises from
      a similarly radial inhomogeneity in the cross-linker concentration. The prospects
      for the NRET technique as a molecular-scale probe of nanostructured microgels are
      also discussed.

PMID- 11516271
TI  - Theoretical and experimental determination of the effects governing the
      transannular Diels-Alder reaction of trans-trans-cis systems with or without
      activation of the dienophile.
AB  - A thorough study of the transannular Diels-Alder (TADA) reaction of trans-trans
      cis macrocyclic trienes was carried out. It led to a better understanding of
      various parameters that govern the TADA reaction in particular and the Diels
      Alder reaction in general. Thus, carbonyl activation of the dienophile and
      substitution of the diene are discussed, as well as the presence of substituents
      on the macrocycle and their respective effects at the transition-state level.

PMID- 11516272
TI  - Highly regioselective, sequential, and multiple palladium-catalyzed arylations of
      vinyl ethers carrying a coordinating auxiliary: an example of a Heck triarylation
      process.
AB  - This article describes the development of new auxiliary-accelerated Heck
      multiarylations by intramolecular presentation of the oxidative addition complex.
      The introduction of a specific, palladium-coordinating dimethylamino group allows
      for the desired chelation-accelerated and chelation-controlled tri- and
      diarylation reactions. We report (a) the first example of a Heck triarylation
      process, (b) highly selective palladium-catalyzed diarylations of alkyl vinyl
      ethers, and (c) a very rapid two-phase protocol for the microwave-assisted
      hydrolysis of amino-substituted, arylated vinyl ethers constituting an entry to
      diarylated ethanals and substituted desoxybenzoins. X-ray structures and product
      patterns support the suggested substrate-controlled Heck reaction pathway. The
      catalyst-directing alkyl dimethylamino functionality was rapidly (1-2 min) and
      efficiently released by microwave hydrolysis after Heck multiarylation reactions.
      The liberated aromatic carbonyl compounds were thereafter isolated and fully
      characterized.

PMID- 11516273
TI  - Quantitative and reversible lectin-induced association of gold nanoparticles
      modified with alpha-lactosyl-omega-mercapto-poly(ethylene glycol).
AB  - Gold nanoparticles (1-10 nm size range) were prepared with an appreciably narrow
      size distribution by in situ reduction of HAuCl(4) in the presence of
      heterobifunctional poly(ethylene glycol) (PEG) derivatives containing both
      mercapto and acetal groups (alpha-acetal-omega-mercapto-PEG). The alpha-acetal
      PEG layers formed on gold nanoparticles impart appreciable stability to the
      nanoparticles in aqueous solutions with elevated ionic strength and also in serum
      containing medium. The PEG acetal terminal group was converted to aldehyde by
      gentle acid treatment, followed by the reaction with p-aminophenyl-beta-D-
      lactopyranoside (Lac) in the presence of (CH(3))(2)NHBH(3). Lac-conjugated gold
      nanoparticles exhibited selective aggregation when exposed to Recinus communis
      agglutinin (RCA(120)), a bivalent lectin specifically recognizing the beta-D
      galactose residue, inducing significant changes in the absorption spectrum with
      concomitant visible color change from pinkish-red to purple. Aggregation of the
      Lac-functionalized gold nanoparticles by the RCA(120) lectin was reversible,
      recovering the original dispersed phase and color by addition of excess
      galactose. Further, the degree of aggregation was proportional to lectin
      concentration, allowing the system to be utilized to quantitate lectin
      concentration with nearly the same sensitivity as ELISA. This simple, yet highly
      effective, derivatization of gold nanoparticles with heterobifunctional PEG
      provides a convenient method to construct various colloidal sensor systems
      currently applied in bioassays and biorecognition.

PMID- 11516274
TI  - Chiral diamines 4: a computational study of the enantioselective deprotonation of
      Boc-pyrrolidine with an alkyllithium in the presence of a chiral diamine.
AB  - The enantioselective deprotonation of N-Boc-pyrrolidine (1) with i-PrLi-(-)
      sparteine has been studied at theoretical levels up through B3P86/6-31G. Four low
      energy intermediate complexes involving i-PrLi-(-)-sparteine and 1 were located
      via geometry optimizations; two of these complexes would lead to abstraction of
      the pro-S hydrogen from 1, and the other two complexes would lead to loss of the
      pro-R hydrogen. The lowest-energy intermediate complex was found to lead to loss
      of the pro-S hydrogen as observed experimentally. Transition states for the
      deprotonations were located using the synchronous transit-guided quasi-Newton
      method. The calculated activation enthalpy for transfer of the pro-S hydrogen
      within the lowest-energy intermediate complex, 10.8 kcal/mol, is reasonable for a
      reaction that occurs at a relatively low temperature, and the calculated kinetic
      hydrogen isotope effect is in agreement with experimental data. The lower
      enantioselectivity observed experimentally for deprotonation of 1 using t-BuLi-(
      )-sparteine is attributed to a transition-state effect due to increased steric
      interaction engendered by the bulky t-BuLi. Replacement of the tert
      butoxycarbonyl group in 1 by a methoxycarbonyl is predicted to result in a slower
      deprotonation with somewhat decreased enantioselectivity. Asymmetric
      deprotonation of 1 using i-PrLi in combination with the C(2)-symmetric diamine,
      (S,S)-1,2-bis(N,N-dimethylamino)cyclohexane, was calculated to be much less
      selective than is the deprotonation mediated by (-)-sparteine as observed
      experimentally. The relative energies of the intermediate complexes were fairly
      well-reproduced by ONIUM calculations in which the sparteine ligand less its
      nitrogen atoms was treated by molecular mechanics and the remainder of the
      complex was treated by quantum mechanics.

PMID- 11516275
TI  - Assembly of metal-organic frameworks from large organic and inorganic secondary
      building units: new examples and simplifying principles for complex structures.
AB  - The secondary building unit (SBU) has been identified as a useful tool in the
      analysis of complex metal-organic frameworks (MOFs). We illustrate its
      applicability to rationalizing MOF crystal structures by analysis of nine new
      MOFs which have been characterized by single-crystal X-ray diffraction.
      Tetrahedral SBUs in Zn(ADC)(2).(HTEA)(2) (MOF-31), Cd(ATC).[Cd(H(2)O)(6)](H2O)(5)
      (MOF-32), and Zn(2)(ATB)(H2O).(H2O)(3)(DMF)(3) (MOF-33) are linked into diamond
      networks, while those of Ni(2)(ATC)(H(2)O)(4).(H2O)(4) (MOF-34) have the
      structure of the Al network in SrAl(2). Frameworks constructed from less
      symmetric tetrahedral SBUs have the Ga network of CaGa(2)O(4) as illustrated by
      Zn(2)(ATC).(C(2)H(5)OH)(2)(H2O)(2) (MOF-35) structure. Squares and tetrahedral
      SBUs in Zn(2)(MTB)(H2O)(2).(DMF)(6)(H2O)(5) (MOF-36) are linked into the PtS
      network, which is the simplest structure type known for the assembly of these
      shapes. The octahedral SBUs found in Zn(2)(NDC)(3).[(HTEA)(DEF)(ClBz)](2) (MOF
      37) form the most common structure for linking octahedral shapes, namely, the
      boron network in CaB(6). New structure types for linking triangular and trigonal
      prismatic SBUs are found in Zn(3)O(BTC)(2).(HTEA)(2) (MOF-38) and
      Zn(3)O(HBTB)(2)(H2O).(DMF)(0.5)(H2O)(3) (MOF-39). The synthesis, crystal
      structure, and structure analysis using the SBU approach are presented for each
      MOF.

PMID- 11516276
TI  - Synthesis and catalytic antibody functionalization of dendrimers.
AB  - Antibody 38C2 catalyzed a retro-aldol process upon dendritic modified aliphatic
      polyesters. This catalytic system was studied in detail and displayed rate
      enhancements, k(cat)/k(uncat), of greater than 10(6). These antibody-catalyzed
      reactions took place in a stepwise manner yielding partially modified aldol
      dendrimers until a fully substituted aldehyde dendrimer was formed. The catalytic
      antibody 38C2 only reacted with surface-exposed aldol moieties and did not
      significantly interact with the core groups for dendrons 4 and 8. For a higher
      generation dendron 8 the rate of unmasking slightly decreased presumably due to
      steric crowding of the aldol functionalities. In addition, catalytic antibody
      38C2 was able to selectively differentiate block-hybrid dendrons and was
      regiospecific in the retro-aldol reaction of dendron 21. This is an inaugural
      report of a catalytic antibody utilizing dendrimers as substrates and suggests
      that antibodies could be used as selective catalysts for the controlled release
      and activation of specific molecules attached to biodegradable polymeric
      materials. Furthermore, this is the first example of catalytic antibody 38C2
      displaying regioselectivity on a multifunctional aldol substrate. Important for
      synthetic applications is the antibody's ability to selectively differentiate
      regions on dendritic substrates and produce partly aldol functionalized dendrons
      under conditions mild enough to avoid beta-elimination.

PMID- 11516277
TI  - First direct structural comparison of complexes of the same metal fragment to
      ketenes in both C,C- and C,O-bonding modes.
AB  - Using a series of Ir(I) and Rh(I) ketene complexes, conclusions about the
      structure and bonding of complexes of the fundamentally important ketene ligand
      class are reached. In a unique comparison of X-ray structures of the same metal
      fragment to ketenes in both the eta(2)-(C,C) and the eta(2)-(C,O) binding mode,
      the Ir-Cl bond distances in complexes of trans-Cl(Ir)[P(i-Pr)(3)](2) to
      phenylketene [4, eta(2)-(C,C)] and diphenylketene [2a, eta(2)-(C,O)] are 2.371(3)
      and 2.285(2) A, respectively. This would be consistent with greater trans
      influence of a ketene ligand bound to a metal through its C=C bond than one
      connected by its C=O bond. Back-bonding of Ir(I) and Rh(I) to diphenylketene was
      assessed using trans-Cl(M)[P(i-Pr)(3)](2)[eta(2)-(C,O)-diphenylketene] (2a and
      2d). Most bond lengths and angles are identical, but slightly greater back
      bonding by Ir(I) is suggested by the somewhat greater deformation of the ketene
      C=C=O system [C-C-O angles are 136.6(4) and 138.9(4) in the Ir and Rh cases 2a
      and 2d, respectively]. Syntheses of new labeled ketenes Ph(2)C=(13)C=O and
      Ph(2)C=C=(18)O and their Ir(I) and Rh(I) complexes are reported, along with the
      generation of an Ir(I) complex of PhCH=(13)C=O. The effects of isotopic
      substitution on infrared absorption data for ketene complexes are presented for
      the first time. Preliminary normal coordinate mode analysis allowed definitive
      assignment of absorptions ascribed to the C-O stretching frequencies of
      coordinated ketenes, which are near the absorptions for aromatic ring systems
      commonly found as substituents on ketenes. For free diphenylketene and four of
      its complexes and a phenylketene complex characterized by X-ray diffraction, the
      magnitude of the (13)C-(13)C coupling between the two ketene carbons is
      correlated to carbon-carbon bond distance.

PMID- 11516278
TI  - Spectroscopic properties and electronic structure of low-spin Fe(III)-alkylperoxo
      complexes: homolytic cleavage of the O-O bond.
AB  - The spectroscopic properties, electronic structure, and reactivity of the low
      spin Fe(III)-alkylperoxo model complex [Fe(TPA)(OH(x))(OO(t)Bu)](x+) (1; TPA =
      tris(2-pyridylmethyl)amine, (t)Bu = tert-butyl, x = 1 or 2) are explored. The
      vibrational spectra of 1 show three peaks that are assigned to the O-O stretch
      (796 cm(-1)), the Fe-O stretch (696 cm(-)(1)), and a combined O-C-C/C-C-C bending
      mode (490 cm(-1)) that is mixed with upsilon(FeO). The corresponding force
      constants have been determined to be 2.92 mdyn/A for the O-O bond which is small
      and 3.53 mdyn/A for the Fe-O bond which is large. Complex 1 is characterized by a
      broad absorption band around 600 nm that is assigned to a charge-transfer (CT)
      transition from the alkylperoxo pi*(upsilon) to a t(2g) d orbital of Fe(III).
      This metal-ligand pi bond is probed by MCD and resonance Raman spectroscopies
      which show that the CT state is mixed with a ligand field state (t(2g) --> e(g))
      by configuration interaction. This gives rise to two intense transitions under
      the broad 600 nm envelope with CT character which are manifested by a pseudo-A
      term in the MCD spectrum and by the shapes of the resonance Raman profiles of the
      796, 696, and 490 cm(-1) vibrations. Additional contributions to the Fe-O bond
      arise from sigma interactions between mainly O-O bonding donor orbitals of the
      alkylperoxo ligand and an e(g) d orbital of Fe(III), which explains the observed
      O-O and Fe-O force constants. The observed homolytic cleavage of the O-O bond of
      1 is explored with experimentally calibrated density functional (DFT)
      calculations. The O-O bond homolysis is found to be endothermic by only 15 to 20
      kcal/mol due to the fact that the Fe(IV)=O species formed is highly stabilized
      (for spin states S = 1 and 2) by two strong pi and a strong sigma bond between
      Fe(IV) and the oxo ligand. This low endothermicity is compensated by the entropy
      gain upon splitting the O-O bond. In comparison, Cu(II)-alkylperoxo complexes
      studied before [Chen, P.; Fujisawa, K.; Solomon, E. I. J. Am. Chem. Soc. 2000,
      122, 10177] are much less suited for O-O bond homolysis, because the resulting
      Cu(III)=O species is less stable. This difference in metal-oxo intermediate
      stability enables the O-O homolysis in the case of iron but directs the copper
      complex toward alternative reaction channels.

PMID- 11516279
TI  - Cationic aluminum alkyl complexes incorporating aminotroponiminate ligands.
AB  - The synthesis, structures, and reactivity of cationic aluminum complexes
      containing the N,N'-diisopropylaminotroponiminate ligand ((i)Pr(2)-ATI(-)) are
      described. The reaction of ((i)Pr(2)-ATI)AlR(2) (1a-e,g,h; R = H (a), Me (b), Et
      (c), Pr (d), (i)Bu (e), Cy (g), CH(2)Ph (h)) with [Ph(3)C][B(C(6)F(5))(4)] yields
      ((i)()Pr(2)-ATI)AlR(+) species whose fate depends on the properties of the R
      ligand. 1a and 1b react with 0.5 equiv of [Ph(3)C][B(C(6)F(5))(4)] to produce
      dinuclear monocationic complexes [([(i)Pr(2)-ATI] AlR)(2)(mu-R)][(C(6)F(5))(4)]
      (2a,b). The cation of 2b contains two ((i)()Pr(2)-ATI)AlMe(+) units linked by an
      almost linear Al-Me-Al bridge; 2a is presumed to have an analogous structure. 2b
      does not react further with [Ph(3)C][B(C(6)F(5))(4)]. However, 1a reacts with 1
      equiv of [Ph(3)C][B(C(6)F(5))(4)] to afford ((i Pr(2)-ATI)Al(C(6)F(5))(mu
      H)(2)B(C(6)F(5))(2) (3) and other products, presumably via C(6)F(5)(-) transfer
      and ligand redistribution of a [((i)()Pr(2)-ATI)AlH][(C(6)F(5))(4)] intermediate.
      1c-e react with 1 equiv of [Ph(3)C][B(C(6)F(5))(4)] to yield stable base-free
      [((i)Pr(2)-ATI)AlR][B(C(6)F(5))(4)] complexes (4c-e). 4c crystallizes from
      chlorobenzene as 4c(ClPh).0.5PhCl, which has been characterized by X-ray
      crystallography. In the solid state the PhCl ligand of 4c(ClPh) is coordinated by
      a dative PhCl-Al bond and an ATI/Ph pi-stacking interaction. 1g,h react with
      [Ph(3)C][B(C(6)F(5))(4)] to yield ((i)Pr(2)-ATI)Al(R)(C(6)F(5)) (5g,h) via
      C(6)F(5)(-) transfer of [((i)Pr(2)-ATI)AlR][(BC(6)F(5))(4)] intermediates. 1c,h
      react with B(C(6)F(5))(3) to yield ((i)Pr(2)-ATI)Al(R)(C(6)F(5)) (5c,h) via
      C(6)F(5)(-) transfer of [((i)Pr(2)-ATI)AlR][RB(C(6)F(5))(3)] intermediates. The
      reaction of 4c-e with MeCN or acetone yields [((i)Pr(2)
      ATI)Al(R)(L)][B(C(6)F(5))(4)] adducts (L = MeCN (8c-e), acetone (9c-e)), which
      undergo associative intermolecular L exchange. 9c-e undergo slow beta-H transfer
      to afford the dinuclear dicationic alkoxide complex [(((i)Pr(2)-ATI)Al(mu
      O(i)()Pr))(2)][B(C(6)F(5))(4)](2) (10) and the corresponding olefin. 4c-e
      catalyze the head-to-tail dimerization of tert-butyl acetylene by an
      insertion/sigma-bond metathesis mechanism involving [((i)Pr(2)
      ATI)Al(C=C(t)Bu)][B(C(6)F(5))(4)] (13) and [((i)Pr(2)
      ATI)Al(CH=C((t)()Bu)C=C(t)Bu)][B(C(6)F(5))(4)] (14) intermediates. 13
      crystallizes as the dinuclear dicationic complex [([(i Pr(2)-ATI]Al(mu
      C=C(t)Bu))(2)][B(C(6)F(5))(4)](2).5PhCl from chlorobenzene. 4e catalyzes the
      polymerization of propylene oxide and 2a catalyzes the polymerization of methyl
      methacrylate. 4c,e react with ethylene-d(4) by beta-H transfer to yield
      [((i)Pr(2)-ATI)AlCD(2)CD(2)H][B(C(6)F(5))(4)] initially. Polyethylene is also
      produced in these reactions by an unidentified active species.

PMID- 11516280
TI  - Sonochemical preparation of supported hydrodesulfurization catalysts.
AB  - Sonochemical preparation of Co and Ni promoted MoS(2) supported on alumina was
      achieved by high-intensity ultrasonic irradiation of isodurene solutions
      containing molybdenum carbonyl, dicobalt octacarbonyl, elemental sulfur, and
      Al(2)O(3) or Ni-Al(2)O(3) under Ar flow. The sonochemically prepared catalysts
      were characterized by elemental analysis, XPS, SEM, TEM, and XEDS, and
      hydrodesulfurization (HDS) activity evaluated for thiophene and dibenzothiophene
      substrates. The TEM studies on the sonochemically prepared catalysts indicate the
      formation of layered hexagonal MoS(2) (lattice fringes approximately 6.2 A) on
      the alumina support. The sonochemically prepared Co-Mo-S/Al(2)O(3), Ni-Mo
      S/Al(2)O(3), and Co-Ni-Mo-S/Al(2)O(3) are extremely active catalysts for the HDS
      of thiophene and dibenzothiophene, with activities severalfold those of
      comparable commercial catalysts under identical conditions. The layered structure
      of MoS(2) remained intact after 120 h of HDS, and the catalyst is reusable.

PMID- 11516281
TI  - Oxidative addition of the imidazolium cation to zerovalent Ni, Pd, and Pt: a
      combined density functional and experimental study.
AB  - Oxidative addition of different imidazolium cations to zerovalent group 10
      metals, to afford heterocyclic carbene complexes, has been investigated by both
      density functional theory (DFT) and experimental studies. The theoretical
      analysis shows that addition of imidazoliums to Pt(0) and Ni(0) is more
      exothermic than to Pd(0), and Ni(0) is predicted to react with a much lower
      barrier than either Pt(0) or Pd(0). Strongly basic supporting ligands on the
      metal, as well as cis-chelating ligands, increase the exothermicity of the
      reaction and also lower the activation barrier. The addition of 2-H imidazoliums
      is easier and more exothermic than addition of 2-alkylimidazoliums, and a halo
      imidazolium is expected to further lower the barrier to oxidative addition and
      increase the exothermicity. The DFT results show that all three of the metals
      should be able to oxidatively add imidazolium cations under appropriate
      conditions. Experimental studies confirmed that oxidative addition is possible,
      and a number of Pt- and Pd-carbene complexes were prepared via oxidative addition
      of imidazolium salts to M(0) precursors. Most significantly, oxidative addition
      of 2-H azolium salts was found to readily occur, and the reaction of 1,3
      dimethylimidazolium tetrafluoroborate with Pt(PPh(3))(2) and Pt(PCy(3))(2)
      affords [PtH(dmiy)(PPh(3))(2)]BF(4) (10) and [PtH(dmiy)(PCy(3))(2)]BF(4) (11),
      while reaction between 3,4-dimethylthiazolium tetrafluoroborate and Pt(PCy(3))(2)
      yields [PtH(dmty)(PCy(3))(2)]BF(4) (12) (dmiy = 1,3-dimethylimidazolin-2-ylidene,
      dmty = 3,4-dimethylthiazolin-2-ylidene). Addition of 2-iodo-1,3,4,5
      tetramethylimidazolium tetrafluoroborate to Pt(PPh(3))(4) or Pd(dcype)(dba)
      yields [PtI(tmiy)(PPh(3))(2)]BF(4) (9) and [PdI(tmiy)(dcype)]BF(4) (14),
      respectively (tmiy = 1,3,4,5-tetramethylimidazolin-2-ylidene, dcype = 1,3
      bis(dicyclohexylphosphino)ethane)). X-ray crystal structures are reported for
      complexes 9 and 11 (cis and trans). These studies clearly show for the first time
      that oxidative addition of imidazolium and thiazolium cations is possible, and
      the results are discussed in terms of the ramifications for catalysis in
      imidazolium-based ionic liquids with both carbene-based and non-carbene-based
      complexes.

PMID- 11516282
TI  - Photophysics of pi-conjugated metal-organic oligomers: aryleneethynylenes that
      contain the (bpy)Re(CO)(3)Cl chromophore.
AB  - A comprehensive study of a series of four monodisperse, metal-organic pi
      conjugated oligomers of varying length is reported. The oligomers are based on
      the aryleneethynylene architecture, and they contain a 2,2'-bipyridine-5,5'-diyl
      (bpy) metal binding unit. The photophysical properties of the free oligomers and
      their complexes with the (L)Re(I)(CO)(3)X chromophore (where L = the bpy-oligomer
      and X = Cl or NCCH(3)) were explored by a variety of methods including
      electrochemistry, UV-visible absorption, variable temperature photoluminescence
      (PL), transient absorption (TA), and time-resolved electron paramagnetic
      spectroscopy (TREPR). The absorption of the free oligomers and the metal
      complexes is dominated by the pi,pi* transitions of the pi-conjugated oligomers.
      The free oligomers feature a strong blue fluorescence that is quenched entirely
      in the (L)Re(I)(CO)(3)X complexes. The metal-oligomers feature a weak, relatively
      long-lived red photoluminescence that is assigned to emission from both the
      (3)pi,pi* manifold of the pi-conjugated system and the dpi Re --> pi* bpy
      oligomer metal-to-ligand charge transfer ((3)MLCT) state. On the basis of a
      detailed analysis of the PL, TA, and TREPR results an excited-state model is
      developed which indicates that the oligomer-based (3)pi,pi* state and the (3)MLCT
      states are in close energetic proximity. Consequently the photophysical
      properties reflect a composite of the properties of the two excited-state
      manifolds.

PMID- 11516283
TI  - Monodithiolene molybdenum(V, VI) complexes: a structural analogue of the oxidized
      active site of the sulfite oxidase enzyme family.
AB  - The active sites of the xanthine oxidase and sulfite oxidase enzyme families
      contain one pterin-dithiolene cofactor ligand bound to a molybdenum atom.
      Consequently, monodithiolene molybdenum complexes have been sought by exploratory
      synthesis for structural and reactivity studies. Reaction of
      [MoO(S(2)C(2)Me(2))(2)](1-) or [MoO(bdt)(2)](1-) with PhSeCl results in removal
      of one dithiolate ligand and formation of [MoOCl(2)(S(2)C(2)Me(2))](1-) (1) or
      [MoOCl(2)(bdt)](1-) (2), which undergoes ligand substitution reactions to form
      other monodithiolene complexes [MoO(2-AdS)(2)(S(2)C(2)Me(2))](1-) (3),
      [MoO(SR)(2)(bdt)](1-) (R = 2-Ad (4), 2,4,6-Pr(i)(3)C(6)H(2) (5)), and
      [MoOCl(SC(6)H(2)-2,4,6-Pr(i)(3))(bdt)](1-) (6) (Ad = 2-adamantyl, bdt = benzene
      1,2-dithiolate). These complexes have square pyramidal structures with apical oxo
      ligands, exhibit rhombic EPR spectra, and 3-5 are electrochemically reducible to
      Mo(IV)O species. Complexes 1-6 constitute the first examples of five-coordinate
      monodithiolene Mo(V)O complexes; 6 approaches the proposed structure of the high
      pH form of sulfite oxidase. Treatment of [MoO(2)(OSiPh(3))(2)] with Li(2)(bdt) in
      THF affords [MoO(2)(OSiPh(3))(bdt)](1-) (8). Reaction of 8 with 2,4,6
      Pr(i)(3)C(6)H(2)SH in acetonitrile gives [MoO(2)(SC(6)H(2)-2,4,6
      Pr(i)(3))(bdt)](1-) (9, 55%). Complexes 8 and 9 are square pyramidal with apical
      and basal oxo ligands. With one dithiolene and one thiolate ligand of a square
      pyramidal Mo(VI)O(2)S(3) coordination unit, 9 closely resembles the oxidized
      sites in sulfite oxidase and assimilatory nitrate reductase as deduced from
      crystallography (sulfite oxidase) and Mo EXAFS. The complex is the first
      structural analogue of the active sites in fully oxidized members of the sulfite
      oxidase family. This work provides a starting point for the development of both
      structural and reactivity analogues of members of this family.

PMID- 11516285
TI  - Cation-pi interactions and the gas-phase thermochemistry of the
      Na(+)/phenylalanine complex.
AB  - The complex of Na(+) with phenylalanine (Phe) is a prototype for the
      participation of cation-pi interactions in metal-ion binding to biological
      molecules. A recent comparison of this complex with the Na(+)/alanine (Na(+)/Ala)
      counterpart suggested only a small contribution of the phenyl ring interaction to
      binding, casting doubt on the extent of the cation-pi effect. The present work
      reexamines this thermochemistry using ligand-exchange equilibrium measurements in
      the Fourier transform ion cyclotron resonance (FT-ICR) ion trapping mass
      spectrometer. An increment of 7 +/- 2 kcal mol(-1) was found in the Ala/Phe
      comparison of binding enthalpies, confirming the importance of cation-pi binding
      enhancement in the Phe case. Absolute Na(+) binding enthalpies of 38 +/- 2 and 45
      +/- 2 kcal mol(-1) were assigned for Ala and Phe, respectively, using pyridine as
      the thermochemical reference ligand. All of these results were supported by
      quantum calculations using both density functional and Hartree-Fock/MP2 methods,
      improved in several respects over previous calculations. Alanine methyl ester
      (AlaMe) was also observed, and found to have an Na(+) ion affinity larger by 2.3
      kcal mol(-1) than Ala. New, lower energy conformations of neutral Phe were
      discovered in the computations.

PMID- 11516284
TI  - Use of WO(4)(2-) on layered double hydroxides for mild oxidative bromination and
      bromide-assisted epoxidation with H(2)O(2).
AB  - Tungstate, exchanged on a (Ni,Al) layered double hydroxide, is applied as a
      heterogeneous catalyst in the oxidation of bromide with H(2)O(2) and the ensuing
      electrophilic bromination of olefins. The high halogenation activity of the
      catalyst in essentially neutral conditions mimicks the activity of V
      bromoperoxidase enzymes. In water, aromatic and aliphatic olefins are selectively
      converted to bromohydrins; in methanol, methoxybromides are produced. In
      appropriate solvent conditions, the bromohydroxylation of geminally di-, tri-,
      and tetrasubstituted olefins proceeds via dehydrobromination to the epoxide.
      Evidence for this mechanism is provided by kinetic and labeling experiments. This
      one-pot alternative for the two-step halohydrin epoxidation process is enabled by
      the mild pH conditions; bromide is effective in substoichiometric, catalytic
      amounts. All new catalytic procedures are characterized by a high oxidative
      stability of the catalyst, high productivity of the catalyst on weight basis,
      high W turnover frequencies in ambient conditions (up to 50 mol of product per W
      per h), and high chemo-, regio-, and stereoselectivities.

PMID- 11516286
TI  - o-Quinone methide as alkylating agent of nitrogen, oxygen, and sulfur
      nucleophiles. The role of H-bonding and solvent effects on the reactivity through
      a DFT computational study.
AB  - The reactivity of the alkylating agent o-quinone methide (o-QM) toward NH(3),
      H(2)O, and H(2)S, prototypes of nitrogen-, oxygen-, and sulfur-centered
      nucleophiles, has been studied by quantum chemical methods in the frame of DF
      theory (B3LYP) in reactions modeling its reactivity in water with biological
      nucleophiles. The computational analysis explores the reaction of NH(3), H(2)O,
      and H(2)S with o-QM, both free and H-bonded to a discrete water molecule, with
      the aim to rationalize the specific and general effect of the solvent on o-QM
      reactivity. Optimizations of stationary points were done at the B3LYP level using
      several basis sets [6-31G(d), 6-311+G(d,p), adding d and f functions to the S
      atom, 6-311+G(d,p),S(2df), and AUG-cc-pVTZ]. The activation energies calculated
      for the addition reactions were found to be reduced by the assistance of a water
      molecule, which makes easier the proton-transfer process in these alkylation
      reactions by at least 12.9, 10.5, and 6.0 kcal mol(-1) [at the B3LYP/AUG-cc
      pVTZ//B3LYP/6-311+G(d,p) level], for ammonia, water, and hydrogen sulfide,
      respectively. A proper comparison of an uncatalyzed with a water-catalyzed
      reaction mechanism has been made on the basis of activation Gibbs free energies.
      In gas-phase alkylation of ammonia and water by o-QM, reactions assisted by an
      additional water molecule H-bonded to o-QM (water-catalyzed mechanism) are
      favored over their uncatalyzed counterparts by 5.6 and 4.0 kcal mol(-1) [at the
      B3LYP/6-311+G(d,p) level], respectively. In contrast, the hydrogen sulfide
      alkylation reaction in the gas phase shows a slight preference for a direct
      alkylation without water assistance, even though the free energy difference
      (DeltaDeltaG(#)) between the two reaction mechanisms is very small (by 1.0 kcal
      mol(-1) at the B3LYP/6-311+G(d,p),S(2df) level of theory). The bulk solvent
      effect, evaluated by the C-PCM model, significantly modifies the relative
      importance of the uncatalyzed and water-assisted alkylation mechanism by o-QM in
      comparison to the case in the gas phase. Unexpectedly, the uncatalyzed mechanism
      becomes highly favored over the catalyzed one in the alkylation reaction of
      ammonia (by 7.0 kcal mol(-1)) and hydrogen sulfide (by 4.0 kcal mol(-1)). In
      contrast, activation induced by water complexation still plays an important role
      in the o-QM hydration reaction in water as solvent.

PMID- 11516287
TI  - Proton positions in the Mn(2+) binding site of concanavalin A as determined by
      single-crystal high-field ENDOR spectroscopy.
AB  - High-field (95 GHz) pulsed EPR and electron-nuclear double resonance (ENDOR)
      techniques have been used for the first time to determine coordinates of ligand
      protons of a high-spin metal center in a protein single crystal. The protein
      concanavalin A contains a Mn(2+) ion which is coordinated to two water molecules,
      a histidine residue, and three carboxylates. Single crystals of concanavalin A
      were grown in H(2)O and in D(2)O to distinguish the exchangeable water protons
      from the nonexchangeable protons of the imidazole group. Distinct EPR transitions
      were selected by performing the ENDOR measurements at different magnetic fields
      within the EPR spectrum. This selection, combined with the large thermal
      polarization achieved at 4.5 K and a magnetic field of approximately 3.4 T
      allowed us to assign the ENDOR signals to their respective M(S) manifolds, thus
      providing the signs of the hyperfine couplings. Rotation patterns were acquired
      in the ac and ab crystallographic planes. Two distinct crystallographic sites
      were identified in each plane, and the hyperfine tensors of two of the imidazole
      protons and the four water protons were determined by simulations of the rotation
      patterns. All protons have axially symmetric hyperfine tensors and, by applying
      the point-dipole approximation, the positions of the various protons relative to
      the Mn(2+) ion were determined. Likewise, the water protons involved in H-bonding
      to neighboring residues were identified using the published, ultrahigh-resolution
      X-ray crystallographic coordinates of the protein (Deacon et al. J. Chem. Soc.,
      Faraday Trans. 1997, 93(24), 4305-4312).

PMID- 11516289
TI  - New thermal reactions of deuterium-labeled bicyclo[3.2.O]hept-2-enes: bicyclic
      skeletal inversion and epimerization at C7.

PMID- 11516288
TI  - Rate constant dependence on the size of aldehydes in the NO(3) + aldehydes
      reaction. An explanation via quantum chemical calculations and CTST.
AB  - The reactions of NO(3) with formaldehyde, acetaldehyde, propanal, n-butanal, and
      isobutanal have been modeled using accurate ab initio and hybrid DFT methods with
      large basis sets. The results clearly indicate that the reaction is a simple
      aldehydic H atom abstraction; no adduct was found to support the idea of a
      complex mechanism. Alternative hydrogen abstractions were modeled for the alpha
      carbon hydrogen atoms and for the Cbeta of n-butanal; the differences in
      activation energies ruled out the possibility that competitive abstraction could
      be responsible for the anomalous increase of the rate constants with the size of
      aldehydes. The anomalous behavior was found to be a consequence of the
      preexponential factor increase, due to the enlargement of the internal rotation
      partition functions with the size of the aldehydes. The reaction rate constants,
      calculated using the conventional transition-state theory as applied to a
      proposed simple mechanism, reproduce remarkably well the reported experimental
      results. Consideration of the internal rotation partition functions is shown to
      be essential for the determination of the preexponential parameters and thus for
      the correct calculation of the rate constants. The tunneling correction was found
      negligible due to the features of the transition vector.

PMID- 11516290
TI  - A new multicomponent coupling of aldehydes, amides, and dienophiles: atom
      efficient one-pot synthesis of highly substituted cyclohexenes and
      cyclohexadienes.

PMID- 11516291
TI  - Oxa-cope rearrangement of silenes thermally generated from 1,2
      bis[tris(trimethylsilyl)silylcarbonyl]alkanes.

PMID- 11516292
TI  - A luminescent metalloreceptor exhibiting remarkably high selectivity for Mg(2+)
      over Ca(2+).

PMID- 11516294
TI  - Diffusive transport of micelles and monomeric solutes in supercritical CO(2).

PMID- 11516293
TI  - Catalyst design by interpolation in the periodic table: bimetallic ammonia
      synthesis catalysts.

PMID- 11516295
TI  - Reaction of lithium aluminum hydride with elemental selenium: its application as
      a selenating reagent into organic molecules.

PMID- 11516296
TI  - Palladium-catalyzed alpha-arylation of esters and protected amino acids.

PMID- 11516297
TI  - Monitoring chemical transformations at buried organic interfaces by electric
      force microscopy.

PMID- 11516298
TI  - An electronic nose transducer array of vapoluminescent platinum(II) double salts.

PMID- 11516299
TI  - Regio- and stereochemical control in bis-functionalization-cyclization: use of
      alleneyne precursors for carbocyclic and heterocyclic synthesis.

PMID- 11516300
TI  - Phase transition of zeolite RHO at high-pressure.

PMID- 11516302
TI  - Isolated Ir(V) boryl complexes and their reactions with hydrocarbons.

PMID- 11516301
TI  - Mukaiyama aldol-Prins cyclization cascade reaction: a formal total synthesis of
      leucascandrolide A.

PMID- 11516303
TI  - Reactivity of a tantalum-lithium alkylidene supported by an anionic
      triazacyclononane ligand.

PMID- 11516304
TI  - On the formation of the thermotropic cubic phase: insights from monoacetylide
      complexes of Pt(II).

PMID- 11516305
TI  - The reversible formation of the enolate of benzocyclobutenone under aqueous
      conditions.

PMID- 11516306
TI  - Biomimetic stabilization of helical structure in a synthetic polymer by means of
      intramolecular hydrogen bonds.

PMID- 11516307
TI  - Methylaminomethylidyne: a stable intermediate formed on the Pt(III) surface from
      the N-protonation of methyl isocyanide.

PMID- 11516309
TI  - Hydrogen bonding and O(2) affinity of hemoglobins.

PMID- 11516308
TI  - C-methyltransferase and cyclization domain activity at the intraprotein PK/NRP
      switch point of yersiniabactin synthetase.

PMID- 11516310
TI  - Accelerated arene ligand exchange in areneCr(CO(3)) complexes.

PMID- 11516311
TI  - Permanent electric dipole and conformation of unsolvated tryptophan.

PMID- 11516312
TI  - Supramolecular stabilization of a tris(imidazolyl) Zn-aqua complex evidenced by X
      ray analysis: a structural model for mono-zinc active sites of enzymes.

PMID- 11516313
TI  - A new approach to enantiocontrol and enantioselectivity amplification: chiral
      relay in Diels-Alder reactions.

PMID- 11516315
TI  - Refractive-index-mismatch induced aberrations in single-photon and two-photon
      microscopy and the use of aberration correction.
AB  - We examine the effects of aberrations induced by a refractive index mismatch on
      the signal level and resolution of single-photon (1-p) and two-photon (2-p),
      conventional and confocal scanning microscopes. In particular, we consider the
      aberrations introduced by an interface between oil/glass and water. Resolution is
      defined in terms of enclosed fluorescence, rather than full-width half-maximum,
      revealing more useful information for heavily aberrated point spread functions
      (PSFs). It is shown that, at large focusing depths, the resolution of 2-p
      conventional and 1-p confocal microscopes are almost identical. The benefits of
      aberration correction are examined by removing Zernike aberration modes. With
      aberration correction, the best resolution is found for 1-p confocal and 2-p
      confocal modes. An approximation based upon geometrical optics is also introduced
      which shows that the axial resolution of heavily aberrated PSFs is roughly
      proportional to focusing depth.

PMID- 11516316
TI  - Z-polarized confocal microscopy.
AB  - In light microscopy the transverse nature of the electromagnetic field precludes
      a strongly focused longitudinal field component, thus confining polarization
      spectroscopy and imaging to two dimensions (x,y). Here we describe a simple
      confocal microscopy arrangement that optimizes for signal from molecules with
      transition dipoles oriented parallel to the optic axis. In the proposed
      arrangement, we not only generate a predominant longitudinally (z) polarized
      focal field, but also engineer the detection scheme in such a way that in a bulk
      of randomly oriented molecules, the microscope's effective point-spread function
      is dominated by the contribution of those molecules that are oriented along the
      optic axis. Our arrangement not only implicitly allows for the determination of
      the orientation of transition dipoles of single molecules in three dimensions,
      but also highlights the contribution of z-oriented molecules in three-dimensional
      imaging.

PMID- 11516317
TI  - Second-harmonic imaging microscopy of living cells.
AB  - Second harmonic generation (SHG) has been developed in our laboratories as a high
      resolution nonlinear optical imaging microscopy for cellular membranes and intact
      tissues. SHG shares many of the advantageous features for microscopy of another
      more established nonlinear optical technique: two-photon excited fluorescence
      (TPEF). Both are capable of optical sectioning to produce three-dimensional
      images of thick specimens and both result in less photodamage to living tissue
      than confocal microscopy. SHG is complementary to TPEF in that it uses a
      different contrast mechanism and is most easily detected in the transmitted light
      optical path. It can be used to image membrane probes with high membrane
      specificity and displays extraordinary sensitivity in reporting membrane
      potential; it also has the ability to image highly ordered structural proteins
      without any exogenous labels.

PMID- 11516318
TI  - Fluorescence resonance energy transfer microscopy: a mini review.
AB  - Fluorescence resonance energy transfer (FRET) microscopy is a better method than
      the x-ray diffraction, nuclear magnetic resonance, or electron microscopy for
      studying the structure and localization of proteins under physiological
      conditions. In this paper, we describe four different light microscopy techniques
      to visualize the interactions of the transcription factor CAATT/enhancer binding
      protein alpha (C/EBPalpha) in living pituitary cells. In wide-field, confocal,
      and two-photon microscopy the FRET image provides two-dimensional spatial
      distribution of steady-state protein-protein interactions. The two-photon imaging
      technique provides a better FRET signal (less bleedthrough and photobleaching)
      compared to the other two techniques. This information, although valuable, falls
      short of revealing transient interactions of proteins in real time. The
      fluorescence lifetime methods allow us to monitor FRET signals at the moment of
      the protein interactions at a resolution on the order of subnanoseconds,
      providing high temporal, as well as spatial resolution. This paper will provide a
      brief review of the above-mentioned FRET techniques.

PMID- 11516319
TI  - Spatially modulated illumination microscopy: online visualization of intensity
      distribution and prediction of nanometer precision of axial distance measurements
      by computer simulations.
AB  - During the last years, measurements considerably beyond the conventional "Abbe
      Limit" of optical resolution in far field light microscopy were realized by
      several light microscopical approaches. Point spread function (PSF) engineering,
      spectral precision distance microscopy (SPDM), and related methods were used to
      demonstrate the feasibility of such measurements. SPDM allows the measurement of
      position and multiple distances between point-like fluorescent objects of
      different spectral signatures far below the optical resolution criterion as
      defined by the full width at half maximum of the PSF. Here, we report a software
      method to obtain online visualization of light distribution in the lateral and
      axial direction of any object detected in a spatially modulated illumination
      (SMI) microscope. This strongly facilitates routine application of SMI
      microscopy. The software was developed using Microsoft Visual C++ running on
      Windows NT. Furthermore, some aspects of the theoretical limits of the SPDM
      method were studied by virtual microscopy. For the case of SMI microscopy the
      precision of axial distance measurements was studied, taking into account photon
      statistics and image analysis procedures. The results indicate that even under
      low fluorescence intensity conditions typical for biological structure research,
      precise distance measurements in the nanometer range can be determined, and that
      axial distances in the order of 40 nm are detectable with such precision.

PMID- 11516321
TI  - Resolution of multiple green fluorescent protein color variants and dyes using
      two-photon microscopy and imaging spectroscopy.
AB  - The imaging of living cells and tissues using laser-scanning microscopy is
      offering dramatic insights into the spatial and temporal controls of biological
      processes. The availability of genetically encoded labels such as green
      fluorescent protein (GFP) offers unique opportunities by which to trace cell
      movements, cell signaling or gene expression dynamically in developing embryos.
      Two-photon laser scanning microscopy (TPLSM) is ideally suited to imaging cells
      in vivo due to its deeper tissue penetration and reduced phototoxicity; however,
      in TPLSM the excitation and emission spectra of GFP and its color variants [e.g.,
      CyanFP (CFP); yellowFP (YFP)] are insufficiently distinct to be uniquely imaged
      by conventional means. To surmount such difficulties, we have combined the
      technologies of TPLSM and imaging spectroscopy to unambiguously identify CFP,
      GFP, YFP, and redFP (RFP) as well as conventional dyes, and have tested the
      approach in cell lines. In our approach, a liquid crystal tunable filter was used
      to collect the emission spectrum of each pixel within the TPLSM image. Based on
      the fluorescent emission spectra, supervised classification and linear unmixing
      analysis algorithms were used to identify the nature and relative amounts of the
      fluorescent proteins expressed in the cells. In a most extreme case, we have used
      the approach to separate GFP and fluorescein, separated by only 7 nm, and appear
      somewhat indistinguishable by conventional techniques. This approach offers the
      needed ability to concurrently image multiple colored, spectrally overlapping
      marker proteins within living cells.

PMID- 11516320
TI  - Two-photon microscopy and spectroscopy based on a compact confocal scanning head.
AB  - We have combined a confocal laser scanning head modified for TPE (two-photon
      excitation) microscopy with some spectroscopic modules to study single molecules
      and molecular aggregates. The behavior of the TPE microscope unit has been
      characterized by means of point spread function measurements and of the
      demonstration of its micropatterning abilities. One-photon and two-photon mode
      can be simply accomplished by switching from a mono-mode optical fiber (one
      photon) coupled to conventional laser sources to an optical module that allows IR
      laser beam (two-photon/TPE) delivery to the confocal laser scanning head. We have
      then described the characterization of the two-photon microscope for
      spectroscopic applications: fluorescence correlation, lifetime and fluorescence
      polarization anisotropy measurements. We describe the measurement of the response
      of the two-photon microscope to the light polarization and discuss fluorescence
      polarization anisotropy measurements on Rhodamine 6G as a function of the
      viscosity and on a globular protein, the Beta-lactoglobulin B labeled with Alexa
      532 at very high dilutions. The average rotational and translational diffusion
      coefficients measured with fluorescence polarization anisotropy and fluorescence
      correlation methods are in good agreement with the protein size, therefore
      validating the use of the microscope for two-photon spectroscopy on biomolecules.

PMID- 11516322
TI  - Studies on the mechanism of action of a targeted chemotherapeutic drug in living
      cancer cells by two photon laser scanning microspectrofluorometry.
AB  - In this study, we present a spectroscopic study of the entry pattern of a
      chemotherapeutic drug (AN-152) and its carrier hormone ([D-Lys(6)]LH-RH) into
      living cancer cells, with the help of our two-photon probes and a home-built
      localized microspectrofluorometer coupled with two photon laser scanning
      microscope (TPLSM). Due to the inherent localization ability of TPLSM, we were
      able to identify the drug and carrier location in different compartments of the
      cancer cells in vitro. The apparent doxorubicin-assisted nucleic accumulation of
      AN-152 suggests a possible nuclear action of the drug on cell proliferation.

PMID- 11516323
TI  - Imaging of whole tumor cut sections using a novel scanning beam confocal
      fluorescence MACROscope.
AB  - Hypoxia caused by inadequate structure and function of the tumor vasculature has
      been found to negatively determine the prognosis of cancer patients. Hence,
      understanding the biological basis of tumor hypoxia is of significant clinical
      interest. To study solid tumor microenvironments in sufficient detail, large
      areas (several mm in diameter) need to be imaged at microm resolutions. We have
      used a novel confocal scanning laser MACROscope (CSLM) capable of acquiring
      images over fields of view up to 2cm x 2cm. To demonstrate its performance,
      frozen sections from a cervical carcinoma xenograft were triple labeled for
      tissue hypoxia, blood vessels and hypoxia-inducible transcription factor 1 alpha
      (HIF-1alpha), imaged using the CSLM and compared to images obtained using a
      standard epifluorescence microscope imaging system. The results indicate that the
      CSLM is a useful instrument for imaging tissue-based fluorescence at resolutions
      comparable to standard low-power microscope objectives.

PMID- 11516324
TI  - Influence of pulse duration on ultrashort laser pulse ablation of biological
      tissues.
AB  - Ablation characteristics of ultrashort laser pulses were investigated for pulse
      durations in the range of 130 fs-10 ps. Tissue samples used in the study were
      dental hard tissue (dentin) and water. We observed differences in ablation crater
      morphology for craters generated with pulse durations in the 130 fs-1 ps and the
      5 ps-10 ps range. For the water experiment, the surface ablation and subsequent
      propagation of stress waves were monitored using Mach-Zehnder interferometry. For
      130 fs-1 ps, energy is deposited on the surface while for longer pulses the beam
      penetrates into the sample. Both studies indicate that a transition occurs
      between 1 and 5 ps.

PMID- 11516325
TI  - Ablation spectra of the human cornea.
AB  - Ablation of human corneal tissue with 193 nm excimer laser energy generates
      fluorescence in the near ultraviolet and visible regions of the spectrum. The
      fluorescence spectra from five human corneas were collected during ablation in
      vitro. We find that the fluorescence spectrum changes continuously as the cornea
      is ablated from the epithelial surface towards the endothelium. We reduced the
      dimensionality of the large data set resulting from each cornea by a principal
      components analysis. The three most significant principal component eigenvectors
      suffice to describe the observed spectral evolution, and independent analysis of
      each tissue sample produces a similar set of eigenvectors. The evolution of the
      calculated eigenvector weighting factors during ablation then corresponds to the
      observed spectral evolution. In fact, this evolution is qualitatively consistent
      between corneas. We suggest that this spectral evolution offers promise as a real
      time surgical feedback tool.

PMID- 11516326
TI  - Erbium: yttrium-aluminum-garnet laser induced vapor bubbles as a function of the
      quartz fiber tip geometry.
AB  - BACKGROUND: The use of modern erbium: yttrium-aluminum-garnet (YAG) laser systems
      in opthalmic microsurgery requires a precise knowledge of the size and dynamics
      of the laser induced vapor bubbles. The aim of this work was to clarify the
      possibilities of controlling the vapor bubble shape and size by using an
      optimized fiber tip geometry for various ophthalmic applications with the erbium:
      YAG laser. METHODS: The mid-infrared radiation of free-running erbium: YAG laser
      was coupled optically into means of different low OH(-) quartz fiber tips to
      investigate the vapor bubble formation in water by high-speed photography. The
      core diameter of four fiber tips ranged from 200 up to 940 microm. Fourteen fiber
      tips were polished at an angle graduated from 10 degrees to 70 degrees over the
      full core diameter (seven fiber tips) and over the half core diameter (seven
      fiber tips). Three fiber tips were produced to have a curvature at the distal end
      with curvature radii of 160, 230, and 420 microm. RESULTS: The shape as well as
      the size of erbium: YAG laser induced vapor bubbles can be controlled
      systematically by using adequate fiber tip geometries. In detail, the used
      different angles and curvatures demonstrate that the propagation direction of the
      vapor bubbles can be estimated by optical modeling considering Snell's law and
      the Fresnel laws at a quartz-air boundary. Beside this, the size of a vapor
      bubble can be predetermined by choosing ideal fiber tip geometries to reduce or
      increase the radiant exposure at the distal end of the quartz fiber tip.
      CONCLUSIONS: The good possibility of controlling the shape and size of vapor
      bubbles offers a wider range of new applications, especially in ophthalmic
      microsurgery such as erbium YAG laser vitrectomy.

PMID- 11516327
TI  - Photodisruptive laser nucleation of ultrasonic cavitation for biomedical
      applications.
AB  - Pulses of high intensity laser light, when focused into transparent materials,
      may produce localized electron-ion plasmas through optical breakdown. By
      simultaneously incorporating the resulting volume of vaporized material within
      the focal volume of a high intensity ultrasound source, the photodisruption (1.05
      microm wavelength) void served as a nucleation site for ultrasonic cavitation.
      Dilute suspensions of canine erythrocytes in phosphate buffered saline were
      exposed in a flow-through exposure chamber and the percentage of lysed cells was
      used as a measure of the biologically effective cavitation activity produced in
      the chamber. Brief (about 30 micros) acoustic emissions were detected from the
      photodisruption alone (indicating laser nucleation of bubbles), but the cell
      lysis produced was undetectable against the background. However, combined
      exposure greatly increased both the duration of the acoustic emissions (up to 1.5
      ms) and the amount of cell lysis above an ultrasonic pressure amplitude threshold
      of about 4.3 MPa at 2.5 MHz. The amount of cell lysis (sometimes approaching
      100%) increased with increasing ultrasonic intensity, laser pulse energy and
      laser PRF. Addition of 5% serum albumin enhanced the effect, apparently by
      stabilizing bubbles and nuclei. Photodisruptive laser nucleation of ultrasonic
      cavitation can provide controlled and synergistic enhancement of bioeffects.

PMID- 11516328
TI  - Fluorescence properties of albumin blue 633 and 670 in plasma and whole blood.
AB  - We have determined the fluorescence characteristics of two long wavelength dyes,
      albumin blue 633 (AB633) and 670 (AB670), in plasma and blood to evaluate the
      possibility of making direct fluorescence sensing measurements in blood. Using
      binding and lifetime measurements we were also able to show that these dyes bind
      selectively to human serum albumin (HSA) in plasma and blood. By measuring
      changes in the mean lifetime of AB670 with changes in the HSA concentration, we
      showed that lifetime-based sensing can be used to monitor HSA concentrations
      using these albumin blue dyes. Anisotropy measurements for AB633 and AB670 in
      plasma and blood revealed high anisotropy values for these dyes in these media.
      Exploiting these high anisotropies, we were also able to determine HSA
      concentrations in plasma and blood mimics using changes in AB670 anisotropy with
      HSA concentration. These results show that, apart from being able to make
      fluorescence measurements directly in plasma and blood, it is possible to sense
      directly for specific plasma/blood components using fluorescent probes that bind
      preferentially to them.

PMID- 11516329
TI  - Excitation wavelength-dependent changes in Raman spectra of whole blood and
      hemoglobin: comparison of the spectra with 514.5-, 720-, and 1064-nm excitation.
AB  - Raman spectra of whole blood and oxy-hemoglobin (Hb) were measured under the same
      conditions with visible (514.5 nm) and near-infrared (NIR; 720 and 1064 nm)
      excitation, and the obtained spectra were compared in detail. The Raman spectrum
      of blood excited with visible light is dominated by very intense bands due to
      carotenoids, so that it was difficult to obtain information about Hb from the
      spectrum. The Raman spectra of whole blood and oxy-Hb excited with 720 nm light
      are very close to each other; both spectra are essentially Raman spectra of the
      heme chromophore that is preresonant with Q bands. Qualitative spectral analysis
      including band assignment and investigation of nature of resonance effect were
      carried out for the Raman spectra with 720 nm excitation. The spectra of whole
      blood and oxy-Hb excited with 1064 nm light contain contributions from
      nonresonance Raman spectra of the heme chromophore and Raman spectra of proteins.
      The 1064 nm excited spectra of blood and oxy-Hb are similar to each other but
      different in some features. For example, bands due to protein appear stronger in
      the spectrum of whole blood than in that of oxy-Hb which does not contain protein
      except globin part. The comparison between the 514.5, 720, and 1064 nm excited
      Raman spectra reveal that the excitation wavelength of 720 nm is more practical
      than that of visible light and 1064 nm in the Raman analysis of Hb, such as
      oxygenation, specially in situ measurement.

PMID- 11516330
TI  - Design of synchrotron light source and its beamline dedicated to dual-energy x
      ray computed tomography.
AB  - A synchrotron light source dedicated to medical applications has been designed at
      National Institute of Radiological Sciences. The storage ring, with circumference
      of 80 m, is designed for acceleration of 2.3 GeV and a stored current of 420 mA.
      It is equipped with two multipole wigglers to produce sufficient photon flux in a
      hard x-ray region required for medical applications. The purposes of the
      synchrotron light source are clinical performance of medical diagnoses clinically
      and research and development relating with medical applications. One of the most
      interesting applications for us is dual-energy x-ray computed tomography (CT). It
      gives the information about electron density of human tissue. The information
      plays an important role in advancing heavy-ion radiotherapy of cancers. Electron
      density can be derived from attenuation coefficients measured by different energy
      x rays. In this paper, a practical method of the dual-energy x-ray CT with
      synchrotron radiation is proposed with the theoretical consideration. The
      primitive experiment using monochromatic x rays emitted from radioisotopes proved
      the procedure of analysis mentioned here effective to derive electron densities
      from linear attenuation coefficients for two x rays of a different energy. The
      beamline dedicated to dual-energy x-ray CT is also proposed. It has a multipole
      wiggler as a light source and it mainly consists of a dual crystal monochromator
      and a rotating filter for attenuating photon flux of x rays and two-dimensional
      detector.

PMID- 11516331
TI  - Model behavior.

PMID- 11516332
TI  - The meso-genomic era.

PMID- 11516333
TI  - Fish are rising.

PMID- 11516334
TI  - Eleven years of sexual discovery.

PMID- 11516335
TI  - Distinct gene expression profiles of human type 1 and type 2 T helper cells.
AB  - BACKGROUND: The development and activation of CD4+ helper T cell (Th) subsets
      with distinct patterns of unbalanced production of cytokines play an important
      part in infectious, allergic and autoimmune diseases. Human neonatal cord blood
      CD4+ Th cells can be polarized into type 1 or type 2-like effector cells in vitro
      by culturing them in the presence of interleukin (IL)-12 or IL-4, respectively.
      We have exploited this experimental system to identify marker genes that are
      differentially expressed by polarized Th1 and Th2 cells. An oligonucleotide
      microarray specifically designed to screen for inflammation-related candidate
      genes was used and the differential expression was further validated with a
      quantitative real-time RT-PCR method. RESULTS: In addition to the previously
      described marker genes of Th cells, we report subtle changes in the expression of
      several other genes that represent growth factors, receptors and other signaling
      molecules in polarized Th1 and Th2 cell subsets. Additionally, we describe a
      novel set of genes as Th1/Th2 differentiation markers for cells activated by anti
      CD3 and anti-CD28 antibodies. CONCLUSIONS: This study demonstrates the power of
      the targeted use of microarrays in combination with quantitative real-time RT-PCR
      in identifying and validating new marker genes for gene expression studies.

PMID- 11516336
TI  - Gene trapping identifies transiently induced survival genes during programmed
      cell death.
AB  - BACKGROUND: The existence of a constitutively expressed machinery for death in
      individual cells has led to the notion that survival factors repress this
      machinery and, if such factors are unavailable, cells die by default. In many
      cells, however, mRNA and protein synthesis inhibitors induce apoptosis,
      suggesting that in some cases transcriptional activity might actually impede cell
      death. To identify transcriptional mechanisms that interfere with cell death and
      survival, we combined gene trap mutagenesis with site-specific recombination
      (Cre/loxP system) to isolate genes from cells undergoing apoptosis by growth
      factor deprivation. RESULTS: From an integration library consisting of
      approximately 2 x 106 unique proviral integrations obtained by infecting the
      interleukin-3 (IL-3)-dependent hematopoietic cell line - FLOXIL3 - with U3Cre
      gene trap virus, we have isolated 125 individual clones that converted to factor
      independence upon IL-3 withdrawal. Of 102 cellular sequences adjacent to U3Cre
      integration sites, 17% belonged to known genes, 11% matched single expressed
      sequence tags (ESTs) or full cDNAs with unknown function and 72% had no match
      within the public databases. Most of the known genes recovered in this analysis
      encoded proteins with survival functions. CONCLUSIONS: We have shown that
      hematopoietic cells undergoing apoptosis after withdrawal of IL-3 activate
      survival genes that impede cell death. This results in reduced apoptosis and
      improved survival of cells treated with a transient apoptotic stimulus. Thus,
      apoptosis in hematopoietic cells is the end result of a conflict between death
      and survival signals, rather than a simple death by default.

PMID- 11516337
TI  - Analysis of the myosins encoded in the recently completed Arabidopsis thaliana
      genome sequence.
AB  - BACKGROUND: Three types of molecular motors play an important role in the
      organization, dynamics and transport processes associated with the cytoskeleton.
      The myosin family of molecular motors move cargo on actin filaments, whereas
      kinesin and dynein motors move cargo along microtubules. These motors have been
      highly characterized in non-plant systems and information is becoming available
      about plant motors. The actin cytoskeleton in plants has been shown to be
      involved in processes such as transportation, signaling, cell division,
      cytoplasmic streaming and morphogenesis. The role of myosin in these processes
      has been established in a few cases but many questions remain to be answered
      about the number, types and roles of myosins in plants. RESULTS: Using the motor
      domain of an Arabidopsis myosin we identified 17 myosin sequences in the
      Arabidopsis genome. Phylogenetic analysis of the Arabidopsis myosins with non
      plant and plant myosins revealed that all the Arabidopsis myosins and other plant
      myosins fall into two groups - class VIII and class XI. These groups contain
      exclusively plant or algal myosins with no animal or fungal myosins. Exon/intron
      data suggest that the myosins are highly conserved and that some may be a result
      of gene duplication. CONCLUSIONS: Plant myosins are unlike myosins from any other
      organisms except algae. As a percentage of the total gene number, the number of
      myosins is small overall in Arabidopsis compared with the other sequenced
      eukaryotic genomes. There are, however, a large number of class XI myosins. The
      function of each myosin has yet to be determined.

PMID- 11516338
TI  - A draft annotation and overview of the human genome.
AB  - BACKGROUND: The recent draft assembly of the human genome provides a unified
      basis for describing genomic structure and function. The draft is sufficiently
      accurate to provide useful annotation, enabling direct observations of previously
      inferred biological phenomena. RESULTS: We report here a functionally annotated
      human gene index placed directly on the genome. The index is based on the
      integration of public transcript, protein, and mapping information, supplemented
      with computational prediction. We describe numerous global features of the genome
      and examine the relationship of various genetic maps with the assembly. In
      addition, initial sequence analysis reveals highly ordered chromosomal landscapes
      associated with paralogous gene clusters and distinct functional compartments.
      Finally, these annotation data were synthesized to produce observations of gene
      density and number that accord well with historical estimates. Such a global
      approach had previously been described only for chromosomes 21 and 22, which
      together account for 2.2% of the genome. CONCLUSIONS: We estimate that the genome
      contains 65,000-75,000 transcriptional units, with exon sequences comprising 4%.
      The creation of a comprehensive gene index requires the synthesis of all
      available computational and experimental evidence.

PMID- 11516339
TI  - Isolation, in silico characterization and chromosomal localization of a group of
      cDNAs from ciliated epithelial cells after in vitro ciliogenesis.
AB  - BACKGROUND: Immotile cilia syndrome (ICS) or primary ciliary dyskinesia (PCD) is
      an autosomal recessive disorder in humans in which the beating of cilia and sperm
      flagella is impaired. Ciliated epithelial cell linings are present in many
      tissues. To understand ciliary assembly and motility, it is important to isolate
      those genes involved in the process. RESULTS: Total RNA was isolated from
      cultured ciliated nasal epithelial cells after in vitro ciliogenesis and
      expressed sequenced tags (ESTs) were generated. The functions and locations of 63
      of these ESTs were derived by BLAST from two public databases. These ESTs are
      grouped into various classes. One group has high homology not only with the
      mitochondrial genome but also with one or more chromosomal DNAs, suggesting that
      very similar genes, or genes with very similar domains, are expressed from both
      mitochondrial and nuclear DNA. A second class comprises genes with complete
      homology with part of a known gene, suggesting that they are the same genes. A
      third group has partial homology with domains of known genes. A fourth group,
      constituting 33% of the ESTs characterized, has no significant homology with any
      gene or EST in the database. CONCLUSIONS: We have shown that sufficient
      information about the location of ESTs could be derived electronically from the
      recently completed human genome sequences. This strategy of EST localization
      should be significantly useful for mapping and identification of new genes in the
      forthcoming human genome sequences with the vast number of ESTs in the dbEST
      database.

PMID- 11516340
TI  - Histone variants: are they functionally heterogeneous?
AB  - In most eukaryotes, histones, which are the major structural components of
      chromatin, are expressed as a family of sequence variants encoded by multiple
      genes. Because different histone variants can contribute to a distinct or unique
      nucleosomal architecture, this heterogeneity can be exploited to regulate a wide
      range of nuclear functions, and evidence is accumulating that histone variants do
      indeed have distinct functions.

PMID- 11516341
TI  - Mining mouse microarray data.
AB  - Microarrays of mouse genes are now available from several sources, and they have
      so far given new insights into gene expression in embryonic development, regions
      of the brain and during apoptosis. Microarray data posted on the internet can be
      reanalyzed to study a range of questions.

PMID- 11516342
TI  - Anatomy of a bacterial cell cycle.
AB  - Two recent reports describe mRNA and protein expression patterns in the bacterium
      Caulobacter crescentus. The combined use of DNA microarray and proteomic analyses
      provides a powerful new perspective for unraveling the global regulatory networks
      of this complex bacterium.

PMID- 11516344
TI  - Patterns of community integration 2-5 years post-discharge from brain injury
      rehabilitation.
AB  - Outcome after traumatic brain injury (TBI) is characterized by a high degree of
      variability which has often been difficult to capture in traditional outcome
      studies. The purpose of this study was to describe patterns of community
      integration 2-5 years after TBI. Participants were 208 patients admitted to a
      Brain Injury Rehabilitation Unit between 1991-1995 in Brisbane, Australia. The
      design comprised retrospective data collection and questionnaire follow-up by
      mail. Mean follow-up was 3.5 years. Demographic, injury severity and functional
      status variables were retrieved from hospital records. Community integration was
      assessed using the Community Integration Questionnaire (CIQ), and vocational
      status measured by a self administered questionnaire. Data was analysed using
      cluster analysis which divided the data into meaningful subsets. Based on the CIQ
      subscale scores of home, social and productive integration, a three cluster
      solution was selected, with groups labelled as working (n = 78), balanced (n =
      46) and poorly integrated (n = 84). Although 38% of the sample returned to a high
      level of productive activity and 22% achieved a balanced lifestyle, overall
      community integration was poor for the remainder. This poorly integrated group
      had more severe injury characterized by longer periods of acute care and post
      traumatic amnesia (PTA) and greater functional disability on discharge. These
      findings have implications for service delivery prior to and during the process
      of reintegration after brain injury.

PMID- 11516343
TI  - Inhibitor of apoptosis proteins and their relatives: IAPs and other BIRPs.
AB  - SUMMARY: Apoptosis is a physiological cell death process important for
      development, homeostasis and the immune defence of multicellular animals. The key
      effectors of apoptosis are caspases, cysteine proteases that cleave after
      aspartate residues. The inhibitor of apoptosis (IAP) family of proteins prevent
      cell death by binding to and inhibiting active caspases and are negatively
      regulated by IAP-binding proteins, such as the mammalian protein DIABLO/Smac.
      IAPs are characterized by the presence of one to three domains known as
      baculoviral IAP repeat (BIR) domains and many also have a RING-finger domain at
      their carboxyl terminus. More recently, a second group of BIR-domain-containing
      proteins (BIRPs) have been identified that includes the mammalian proteins Bruce
      and Survivin as well as BIR-containing proteins in yeasts and Caenorhabditis
      elegans. These Survivin-like BIRPs regulate cytokinesis and mitotic spindle
      formation. In this review, we describe the IAPs and other BIRPs, their
      evolutionary relationships and their subcellular and tissue localizations.

PMID- 11516345
TI  - Charges and lengths of stay for acute and inpatient rehabilitation treatment of
      traumatic brain injury 1990-1996.
AB  - This investigation evaluated yearly trends in charges and lengths of stay for
      patients with brain injury in acute care and rehabilitation settings over a 7
      year period. Data was collected from 800 consecutive patients enrolled in four
      NIDRR Model Systems Traumatic Brain Injury programmes. Acute care daily charges
      showed almost routine increases, averaging nearly $550 per year. Conversely,
      lengths of stay generally showed a downward trend, with annual reductions
      averaging 2.25 days. Admission lengths of stay averaged 22-29 days between 1990
      1994. Admissions averaged less than 20 days beginning in 1995, with the 1996
      average of 16 days, nearly half that of the 1993 average. Between 1990-1996,
      average daily rehabilitation charges increased each year, with the rise averaging
      $83 or 7%. The rise in daily rehabilitation charges was offset by corresponding
      decreases in lengths of stay averaging 3.65 days or 8% annually. Increases in
      daily charges for brain injury rehabilitation care were roughly comparable to
      those for general medical care prices. However, the rate of change in acute care
      charges was substantially greater, with annual increases averaging 10% more than
      national medical care prices. The steady downward trend in lengths of stay raises
      serious concerns about the future availability of health care services to persons
      with brain injury.

PMID- 11516346
TI  - Post-traumatic stress disorder symptoms following a head injury: does amnesia for
      the event influence the development of symptoms?
AB  - BACKGROUND: There is controversy as to whether PTSD can develop following a brain
      injury with a loss of consciousness. However, no studies have specifically
      examined the influence of the memories that the individuals may or may not have
      on the development of symptoms. AIMS: To consider how amnesia for the traumatic
      event effects the development and profile of traumatic stress symptoms. METHOD:
      Fifteen hundred case records from an Accident and Emergency Unit were screened to
      identify 371 individuals with traumatic brain injury who were sent questionnaires
      by post. The 53 subsequent valid responses yielded three groups: those with no
      memory (n = 14), untraumatic memories (n = 13) and traumatic memories (n = 26) of
      the index event. The IES-R was used as a screening measure followed by a
      structured interview (CAPS-DX) to determine caseness and provide details of
      symptom profile. RESULTS: Groups with no memories or traumatic memories of the
      index event reported higher levels of psychological distress than the group with
      untraumatic memories. Ratings of PTSD symptoms were less severe in the no memory
      groups compared to those with traumatic memories. CONCLUSIONS: Psychological
      distress was associated with having traumatic or no memories of an index event.
      Amnesia for the event did not protect against PTSD; however, it does appear to
      protect against the severity and presence of specific intrusive symptoms.

PMID- 11516347
TI  - Comparison of pocket-computer memory aids for people with brain injury.
AB  - Two styles of pocket computer memory aid were compared as support for people who
      had sustained non-progressive, closed-head brain injury. A purpose-designed
      interface provided a diary with auditory alarms, a notebook and links between
      diary entries and specific notepages. One computer had a physical keyboard, the
      other did not. Twelve adult volunteers were loaned each computer for 2 months,
      with a 1 month gap between, in counterbalanced order. It was found that all
      participants could use the memory aids, and most (83%) found them useful. Little
      customizing was needed, but amount of use varied widely. Predictors of usage
      included use of other reminding systems before joining the project, and speed in
      calculator addition which may reflect working memory. High users preferred the
      computer with a physical keyboard; low users made more entries with the palm-size
      computer. These data highlight the need to distinguish ability to use from
      willingness to use.

PMID- 11516348
TI  - Early predictors of mortality in penetrating compared with closed brain injury.
AB  - INTRODUCTION: Although brain injury incidence rates have been decreasing, the
      proportion of these injuries which are penetrating has been increasing. This
      study compares mortality amongst persons with penetrating and closed brain
      injuries and explores the relationship of early predictors of mortality. METHODS:
      The study included 795 moderately or severely brain injured individuals
      identified through the UCLA Brain Injury Research Centre. Logistic regression was
      used to predict mortality by GCS level and brain injury type, controlling for
      age, gender, and presence of multiple trauma. RESULTS: Of the 795 individuals,
      110 had penetrating and 685 had closed brain injury. Case fatality rates were
      higher for penetrating than closed injuries for all GCS, gender, age, and cause
      of injury categories. When controlling for GCS level at admission, age, gender,
      and multiple trauma, those with penetrating injuries were 6.6 (95% CI = 3.9-11.1)
      times more likely to die. CONCLUSIONS: As the pool of information about survival
      and recovery from penetrating injuries grows, decisions regarding clinical care
      and prevention activities can be more appropriately focused.

PMID- 11516349
TI  - Depression amongst outpatients with traumatic brain injury.
AB  - The incidence of depression and its association with subject characteristics in
      outpatients with traumatic brain injury (TBI) were investigated. Logistic
      regression was estimated with depressed/not-depressed as the dependent variable
      in 41 outpatients with TBI who filled out the Beck Depression Inventory-II (BDI
      II). Twenty-four of 41 subjects (59%) scored in the depressed categories based on
      BDI-II scores >13. Fourteen (34%) scored in the moderate or severe depression
      categories (BDI>19). Logistic regression demonstrated a positive relationship
      amongst depression and age, female gender, mild TBI, and use of antidepressant
      and stimulant drugs; and a negative relationship between depression and violent
      aetiology of injury. ANOVA demonstrated that individuals with mild TBI were
      significantly older than those with moderate or severe TBI, which might account
      for the association between depression and age. The implications of these results
      are discussed.

PMID- 11516350
TI  - A further study on the sustained attention response to task (SART): the effect of
      age, gender and education.
AB  - The present study aimed to investigate the potential effect of age, gender and
      education upon the theoretically sound measure of sustained attention--Sustained
      Attention Response to Task (SART)--amongst a control sample and patients with
      traumatic brain injury (TBI). The SART is a simple and brief computer-assisted
      programme for assessing sustained attention over a short period of time. Two
      further studies on the use of the SART among the Hong Kong Chinese were
      conducted. In particular, experiment 1 recruited a control group to study the
      potential impact of age, education, and gender upon the performance of the SART.
      Experiment 2 was aimed to establish the discriminative validity of the SART upon
      the attentional slip in a larger sample of patients with TBI and the normal
      controls. The potential impact of age, gender, and education upon the SART
      performance was found to be minimal. In keeping with previous studies, the
      present findings demonstrate that SART is able to discriminate the patients with
      TBI from normal controls.

PMID- 11516351
TI  - Validity of motor tasks for predicting running ability in acquired brain injury.
AB  - INTRODUCTION: Rehabilitation of running following traumatic brain injury (TBI)
      has the potential to enhance quality of life. Retraining of running following TBI
      has not been previously reported in the literature. In response to a lack of
      information about which motor tasks should be included in a retraining programme,
      this study aimed to investigate performance predictors of running ability.
      METHOD: Forty TBI subjects (20 runners and 20 non-runners) performed four
      specific motor tasks which were selected on the basis of theory and clinical
      experience with TBI subjects. The four tasks included bounding onto a leg,
      walking on toes, stepping backwards up a step, and balancing on one leg. Subjects
      were generally extremely severely brain damaged (median post-traumatic amnesia
      >28 days), had suffered multiple leg fractures and had received greater than 8
      months rehabilitation. RESULTS: The four motor tasks differentiated significantly
      between the two groups (p < 0.001) and were all strong predictors of running
      ability. The presence of a non-support phase (NSP) during the bounding task was
      the strongest predictor of running ability. Logistic regression indicated that
      TBI subjects who could execute a NSP into a single bound were 24.6 times more
      likely to be able to run than subjects who could not. When the four tasks were
      used in combination, two tasks were identified by logistic regression: (1)
      ability to execute a free-float phase during a bound, and (2) balancing on one
      leg. All four motor tasks had high retest reliability, with proportional indices
      of reliability ranging from 0.92-0.97. No statistically significant difference
      was found between runners and non-runners for group characteristics such as age,
      severity of injury (length of PTA), orthopaedic leg injuries and time post-injury
      (p > 0.05). These characteristics were not shown to influence the ability to run
      following TBI. CLINICAL IMPLICATIONS: The four motor tasks were strong predictors
      of running ability. Severity and type of injury were not factors influencing
      ability to run. This study provides preliminary evidence about the motor tasks
      which have the potential to be used in a running programme. No casual
      relationship has been identified. The next step is to investigate whether
      training in these tasks is effective in the rehabilitation of running following
      TBI.

PMID- 11516352
TI  - Modeling neuronal assemblies: theory and implementation.
AB  - Models that describe qualitatively and quantitatively the activity of entire
      groups of spiking neurons are becoming increasingly important for biologically
      realistic large-scale network simulations. At the systems and areas modeling
      level, it is necessary to switch the basic descriptional level from single
      spiking neurons to neuronal assemblies. In this article, we present and review
      work that allows a macroscopic description of the assembly activity. We show that
      such macroscopic models can be used to reproduce in a quantitatively exact manner
      the joint activity of groups of spike-response or integrate-and-fire neurons. We
      also show that integral as well as differential equation models of neuronal
      assemblies can be understood within a single framework, which allows a comparison
      with the commonly used assembly-averaged graded-response type of models. The
      presented framework thus enables the large-scale neural network modeler to
      implement networks using computational units beyond the single spiking neuron
      without losing much biological accuracy. This article explains the theoretical
      background as well as the capabilities and the implementation details of the
      assembly approach.

PMID- 11516353
TI  - On a class of support vector kernels based on frames in function Hilbert spaces.
AB  - There has been an increasing interest in kernel-based techniques, such as support
      vector techniques, regularization networks, and gaussian processes. There are
      inner relationships among those techniques, with the kernel function playing a
      central role. This article discusses a new class of kernel functions derived from
      the so-called frames in a function Hilbert space.

PMID- 11516354
TI  - Extraction of specific signals with temporal structure.
AB  - In this work we develop a very simple batch learning algorithm for semiblind
      extraction of a desired source signal with temporal structure from linear
      mixtures. Although we use the concept of sequential blind extraction of sources
      and independent component analysis, we do not carry out the extraction in a
      completely blind manner; neither do we assume that sources are statistically
      independent. In fact, we show that the a priori information about the
      autocorrelation function of primary sources can be used to extract the desired
      signals (sources of interest) from their linear mixtures. Extensive computer
      simulations and real data application experiments confirm the validity and high
      performance of the proposed algorithm.

PMID- 11516355
TI  - Correlation between uncoupled conductance-based integrate-and-fire neurons due to
      common and synchronous presynaptic firing.
AB  - We investigate the firing characteristics of conductance-based integrate-and-fire
      neurons and the correlation of firing for uncoupled pairs of neurons as a result
      of common input and synchronous firing of multiple synaptic inputs. Analytical
      approximations are derived for the moments of the steady state potential and the
      effective time constant. We show that postsynaptic firing barely depends on the
      correlation between inhibitory inputs; only the inhibitory firing rate matters.
      In contrast, both the degree of synchrony and the firing rate of excitatory
      inputs are relevant. A coefficient of variation CV > 1 can be attained with low
      inhibitory firing rates and (Poisson-modulated) synchronized excitatory synaptic
      input, where both the number of presynaptic neurons in synchronous firing
      assemblies and the synchronous firing rate should be sufficiently large. The
      correlation in firing of a pair of uncoupled neurons due to common excitatory
      input is initially increased for increasing firing rates of independent
      inhibitory inputs but decreases for large inhibitory firing rates. Common
      inhibitory input to a pair of uncoupled neurons barely induces correlated firing,
      but amplifies the effect of common excitation. Synchronous firing assemblies in
      the common input further enhance the correlation and are essential to attain
      experimentally observed correlation values. Since uncorrelated common input
      (i.e., common input by neurons, which do not fire in synchrony) cannot induce
      sufficient postsynaptic correlation, we conclude that lateral couplings are
      essential to establish clusters of synchronously firing neurons.

PMID- 11516356
TI  - Attention modulation of neural tuning through peak and base rate.
AB  - This study investigates the influence of attention modulation on neural tuning
      functions. It has been shown in experiments that attention modulation alters
      neural tuning curves. Attention has been considered at least to serve to resolve
      limiting capacities and to increase the sensitivity to attended stimulus, while
      the exact functions of attention are still under debate. Inspired by recent
      experimental results on attention modulation, we investigate the influence of
      changes in the height and base rate of the tuning curve on the encoding accuracy,
      using the Fisher information. Under an assumption of stimulus-conditional
      independence of neural responses, we derive explicit conditions that determine
      when the height and base rate should be increased or decreased to improve
      encoding accuracy. Notably, a decrease in the tuning height and base rate can
      improve the encoding accuracy in some cases. Our theoretical results can predict
      the effective size of attention modulation on the neural population with respect
      to encoding accuracy. We discuss how our method can be used quantitatively to
      evaluate different aspects of attention function.

PMID- 11516357
TI  - Democratic integration: self-organized integration of adaptive cues.
AB  - Sensory integration or sensor fusion -- the integration of information from
      different modalities, cues, or sensors -- is among the most fundamental problems
      of perception in biological and artificial systems. We propose a new architecture
      for adaptively integrating different cues in a self-organized manner. In
      Democratic Integration different cues agree on a result, and each cue adapts
      toward the result agreed on. In particular, discordant cues are quickly
      suppressed and recalibrated, while cues having been consistent with the result in
      the recent past are given a higher weight in the future. The architecture is
      tested in a face tracking scenario. Experiments show its robustness with respect
      to sudden changes in the environment as long as the changes disrupt only a
      minority of cues at the same time, although all cues may be disrupted at one time
      or another.

PMID- 11516358
TI  - An autoassociative neural network model of paired-associate learning.
AB  - Hebbian heteroassociative learning is inherently asymmetric. Storing a forward
      association, from item A to item B, enables recall of B (given A), but does not
      permit recall of A (given B). Recurrent networks can solve this problem by
      associating A to B and B back to A. In these recurrent networks, the forward and
      backward associations can be differentially weighted to account for asymmetries
      in recall performance. In the special case of equal strength forward and backward
      weights, these recurrent networks can be modeled as a single autoassociative
      network where A and B are two parts of a single, stored pattern. We analyze a
      general, recurrent neural network model of associative memory and examine its
      ability to fit a rich set of experimental data on human associative learning. The
      model fits the data significantly better when the forward and backward storage
      strengths are highly correlated than when they are less correlated. This network
      based analysis of associative learning supports the view that associations
      between symbolic elements are better conceptualized as a blending of two ideas
      into a single unit than as separately modifiable forward and backward
      associations linking representations in memory.

PMID- 11516359
TI  - Simple recurrent networks learn context-free and context-sensitive languages by
      counting.
AB  - It has been shown that if a recurrent neural network (RNN) learns to process a
      regular language, one can extract a finite-state machine (FSM) by treating
      regions of phase-space as FSM states. However, it has also been shown that one
      can construct an RNN to implement Turing machines by using RNN dynamics as
      counters. But how does a network learn languages that require counting?
      Rodriguez, Wiles, and Elman (1999) showed that a simple recurrent network (SRN)
      can learn to process a simple context-free language (CFL) by counting up and
      down. This article extends that to show a range of language tasks in which an SRN
      develops solutions that not only count but also copy and store counting
      information. In one case, the network stores information like an explicit storage
      mechanism. In other cases, the network stores information more indirectly in
      trajectories that are sensitive to slight displacements that depend on context.
      In this sense, an SRN can learn analog computation as a set of interdependent
      counters. This demonstrates how SRNs may be an alternative psychological model of
      language or sequence processing.

PMID- 11516360
TI  - Training nu-support vector classifiers: theory and algorithms.
AB  - The nu-support vector machine (nu-SVM) for classification proposed by Scholkopf,
      Smola, Williamson, and Bartlett (2000) has the advantage of using a parameter nu
      on controlling the number of support vectors. In this article, we investigate the
      relation between nu-SVM and C-SVM in detail. We show that in general they are two
      different problems with the same optimal solution set. Hence, we may expect that
      many numerical aspects of solving them are similar. However, compared to regular
      C-SVM, the formulation of nu-SVM is more complicated, so up to now there have
      been no effective methods for solving large-scale nu-SVM. We propose a
      decomposition method for nu-SVM that is competitive with existing methods for C
      SVM. We also discuss the behavior of nu-SVM by some numerical experiments.

PMID- 11516361
TI  - A tighter bound for graphical models.
AB  - We present a method to bound the partition function of a Boltzmann machine neural
      network with any odd-order polynomial. This is a direct extension of the mean
      field bound, which is first order. We show that the third-order bound is strictly
      better than mean field. Additionally, we derive a third-order bound for the
      likelihood of sigmoid belief networks. Numerical experiments indicate that an
      error reduction of a factor of two is easily reached in the region where
      expansion-based approximations are useful.

PMID- 11516362
TI  - Paediatric HIV infection--diagnostic and epidemiological aspects.
AB  - There are currently more than 1.3 million children living with HIV in the world
      today and many more who have been orphaned by the epidemic. This review explores
      the nature of the widening gap in the experience of HIV infection between high-
      and low-income countries. The global epidemiology is described, highlighting the
      burden carried by sub-Saharan Africa and the alarming increase being witnessed in
      the Asia/Pacific region. Most of these infections are acquired vertically and are
      now largely preventable in well-resourced settings, and finding and implementing
      appropriate measures in poorer countries is urgently needed. Finally the ability
      to diagnose paediatric HIV infection is explored, highlighting the difference in
      the implications of doing so in settings with limited resources.

PMID- 11516363
TI  - The metabolic toxicities of antiretroviral therapy.
AB  - Since the adoption of highly active antiretroviral therapy (HAART) in the mid
      1990s, certain metabolic toxicities have been increasingly recognized. These
      include a fat redistribution syndrome (lipohypertrophy, lipoatrophy),
      hyperlipidaemia, altered glucose metabolism and insulin resistance, mitochondrial
      toxicity (presenting as anaemia, myopathy, pancreatitis, neuropathy, hepatic
      steatosis and lactic acidosis), and bone density abnormalities (osteoporosis and
      osteonecrosis). Metabolic complications are principally reported with protease
      inhibitors and nucleoside reverse transcriptase inhibitors, but may be seen with
      all classes of antiretroviral therapy. In this review, we summarize the
      epidemiology, pathogenesis and management of these various toxicities.

PMID- 11516364
TI  - New patient-applied therapy for anogenital warts is rated favourably by patients.
AB  - Our objective was to determine patient attitudes to having genital warts, and
      their perceptions of their treatment with imiquimod and other therapies. As an
      adjunct to a clinical trial in which patients with external genital warts were
      treated with imiquimod 5% cream until their warts cleared or for up to 16 weeks,
      quantitative questionnaires consisting of multiple choice questions and 5-point
      rating scales were completed prior to, and at the end, of the study period. Pre
      study and post-study questionnaires were completed by 902 and 629 patients,
      respectively. Patients expressed a definite concern about genital warts. The
      majority of patients (70%) had been previously treated for genital warts, and
      expressed dissatisfaction with their previous therapies. Of patients treated with
      imiquimod in this study, 82% reported that their warts decreased in size; this
      occurred within the first 4 weeks for 78% of patients. Sixty-one per cent of
      patients perceived that their warts completely cleared within the 16-week
      treatment period. Patients rated imiquimod 5% cream as better than other genital
      wart therapies in terms of overall satisfaction, time to clearance, convenience
      and lack of associated pain. In conclusion, patients rated imiquimod 5% cream as
      an effective treatment which clears warts in an acceptable length of time causing
      minimal pain and is convenient to use.

PMID- 11516365
TI  - Genitourinary medicine services in the United Kingdom are failing to meet current
      demand.
AB  - Recent increases in the incidence of sexually transmitted disease (STD) in the UK
      have given rise to concerns over the ability of genitourinary medicine (GUM)
      services to cope with increased demands. We conducted a postal survey to assess
      the capacity of GUM clinics to meet patient demand for both routine and emergency
      consultations. A questionnaire was sent to all lead GUM physicians in the UK. The
      response rate was 80%. In some clinics, patients had to wait for up to 28 days
      for routine appointments. Urgent appointment patients were seen within 24 h by
      only 54% of clinics and some had to wait for at least one week (5% of clinics).
      Prolonged waiting times were reported nationwide in addition to widely expressed
      concerns about the increasing workload. Additional resources should be made
      available to GUM services if the population's sexual health is to be improved.

PMID- 11516367
TI  - "They never tell you about the consequences": young people's awareness of
      sexually transmitted infections.
AB  - Young people are at risk from sexually transmitted infections (STIs)--the
      incidence of chlamydia in the UK is highest among young women aged 16-19. Despite
      this, young people lack knowledge about STIs and are more aware of the risks of
      unwanted pregnancy than their risk of acquiring an STI. This study used
      qualitative and quantitative methods to examine what teenagers know about STIs,
      their prevention, symptoms, treatment and services. Only one-third of respondents
      recognized chlamydia as an STI. The little knowledge of STIs that was revealed
      was superficial. Few were aware that special services existed for STIs. Condoms
      were seen as contraception, not as a method of preventing infection transmission.
      High teenage pregnancy rates have received much publicity but less attention has
      been paid to rising STI incidence. Programmes aimed at decreasing pregnancy rates
      through adoption of effective hormonal contraception not only fail to address
      STIs but may be detrimental to prevention efforts.

PMID- 11516366
TI  - Long-term clinical benefit after highly active antiretroviral therapy in advanced
      HIV-1 infection, even in patients without immune reconstitution.
AB  - Our objective was to assess, in the clinical setting, the predictors of immune
      reconstitution (IR) and its relation with long-term clinical benefit, in HIV
      patients with advanced disease after highly active antiretroviral therapy (HAART)
      through an observational study. A retrospective cohort study in a clinical
      setting of 383 consecutive adult patients with advanced HIV infection (CD4+ cells
      <200/mm(3) at baseline), starting their first protease inhibitor (PI)-containing
      regimen was observed. Immune reconstitution was defined as CD4 count >200
      cells/mm(3) and an increase > or =100 cells from baseline, anytime since starting
      HAART. Clinical benefit was defined as decreased mortality and reduction in AIDS
      defining events, AIDS-related complex (ARC) events, major infections and
      hospitalization (days spent in hospital). During a mean follow-up of 808 days,
      261 patients (68.1%) achieved IR. About 50% of these patients reached this result
      within one year after starting HAART. In multivariate analysis, predictors of
      immune recovery were sex (female) and baseline CD4 count higher than 50
      cells/mm(3). The group of patients with IR had greater clinical benefit with
      lower mortality, fewer AIDS-defining events, shorter lengths of stay in hospital,
      fewer ARC events and fewer major infections during all the follow-up (P < 0.0001,
      tests for trends). However, although they did less remarkably than the first
      group of patients, even those patients who did not achieve IR experienced a
      significant decrease in the incidence of all the above events, as compared with
      the first and sometimes the second trimester after starting their HIV therapy.
      About 70% of HIV patients with advanced disease achieved IR after starting HAART.
      Such a benefit is a time-dependent effect and may even take more than 2 years to
      occur. Predictors of IR were sex (female) and higher baseline CD4 count (>50
      cells/mm(3)). The patients who achieved immune recovery performed clinically
      better than patients who did not. Also the patients who failed to gain such a
      strong immunological recovery experienced a long-term clinical benefit. This
      suggests that PI-containing regimens, in advanced HIV disease, may produce a
      significant clinical benefit, at least temporary, even for patients who do not
      achieve a substantial immune response.

PMID- 11516368
TI  - Qualitative and quantitative aspects of the ligase chain reaction assay for
      Chlamydia trachomatis in genital tract samples and urines.
AB  - The performance of the ligase chain reaction (LCR) assay for Chlamydia
      trachomatis was evaluated in a genitourinary medicine (GUM) clinic population.
      Its sensitivity was 100%, 91% and 95%, respectively, for cervical, vaginal and
      urine samples from 417 women, when compared with direct fluorescent antibody
      (DFA) staining of cervical samples, and 100% and 91%, respectively, for urethral
      and urine samples from 317 men, when compared with DFA staining of urethral
      smears. An enzyme immunoassay (EIA) was only 65% sensitive for cervical samples.
      Urethral swabs from a number of treated men remained LCR-positive when antigen
      was no longer detectable by DFA staining. An association between quantitative
      data from the LCR assay (i.e. the optical density of samples, measured in
      relation to internal controls and calibrators) and the antigen load of the
      samples, measured by DFA staining, indicated a lack of significant inhibition in
      the LCR assay in this study. This was probably due to freezing of the samples
      before testing. Diluting 20 LCR-positive urines with a range of antigen loads
      resulted in loss of positivity in 3, and a reduction in the signal in 13. The
      implications of the antigen load on the performance of detection assays for
      chlamydia-positive patients are discussed.

PMID- 11516369
TI  - HIV antibody testing among the Hong Kong mainland Chinese cross-border sex
      networking population in Hong Kong.
AB  - The present study reports the results of 2 surveys examining the likelihood of
      performing HIV antibody test among the Hong Kong mainland China traveller
      population. The 2 studies interviewed 1325 and 2074 male adult Hong Kong
      residents. Among those who had had sexual intercourse with a female sex worker
      (FSW) in the past 6 months, 31.1% in the first sample indicated that they
      intended to take an HIV antibody test in the future, whereas 16.4% in the second
      sample reported they had actually taken a blood test for HIV antibody. In both
      samples, no association was found between demographic variables,
      attitudinal/knowledge-related variables and intention to do a blood test for HIV
      antibody and actual testing behaviour. Moreover, in both samples, those who had
      more female sexual partners in the past 6 months were more likely to report an
      intention for HIV test or to have taken an HIV test.

PMID- 11516370
TI  - Intention of residents in internal medicine to care for patients infected with
      HIV at a university hospital in Taiwan.
AB  - The purpose of this study was to investigate internal medicine residents' HIV
      related knowledge and their attitudes towards caring for HIV-infected patients,
      and determine the extent to which these variables influence their care-providing
      intention. A cross-sectional survey was conducted in 56 internal medicine
      residents at a university hospital in Taiwan. Results showed residents' lack of
      sufficient knowledge was reflected by their inaccurate assessment of HIV
      associated risk and their tendency to overuse protective gear in unnecessary
      situations. In general, residents expressed slightly positive attitudes with a
      neutral intention to care for HIV-infected patients. Knowledge and attitudes were
      significantly correlated with intention. The use of stepwise regression analysis
      revealed attitudes accounted for 59% of the variance in intention. Future efforts
      should focus on designing, implementing, and evaluating educational programmes
      that address residents' needs to ensure a solid HIV-related knowledge base,
      support their positive attitudes, address their ambivalent feelings toward
      providing HIV care, and enhance their intention to care for HIV-infected
      patients.

PMID- 11516371
TI  - Genital schistosomiasis.
AB  - Schistosomiasis is the most serious helminthic infection in the United Kingdom.
      Female genital schistosomiasis affects 9-13 million women worldwide, mainly in
      areas where Schistosoma haematobium is endemic. With increasing tourism to these
      areas, this diagnosis is being encountered more frequently in the West. We
      present 2 cases of vulval schistosomiasis that were presented to our department
      in 1999 and 2000.

PMID- 11516372
TI  - The risk of myocardial infarction in HIV-infected patients receiving HAART: a
      case report.
AB  - With the advent of highly active antiretroviral therapy (HAART), HIV-related
      morbidity and mortality has declined. Patients are surviving longer but with
      serious side effects, especially those receiving protease inhibitors (PIs). We
      report a case of a healthy young man receiving triple therapy with typical angina
      symptoms that were not recognized by physicians.

PMID- 11516373
TI  - Molluscum contagiosum--a novel presentation.
AB  - A case history is described of an HIV-seropositive man who presented with a
      swelling on the right cheek and a history of disseminated molluscum contagiosum.
      Electron microscopy of the abscess aspirate showed pox virions indicative of
      molluscum contagiosum. This is an unusual presentation of molluscum contagiosum
      and the authors review the literature of other presentations.

PMID- 11516375
TI  - An audit of the "two glass" test for urethritis.

PMID- 11516376
TI  - Risk factors for human disease emergence.
AB  - A comprehensive literature review identifies 1415 species of infectious organism
      known to be pathogenic to humans, including 217 viruses and prions, 538 bacteria
      and rickettsia, 307 fungi, 66 protozoa and 287 helminths. Out of these, 868 (61%)
      are zoonotic, that is, they can be transmitted between humans and animals, and
      175 pathogenic species are associated with diseases considered to be 'emerging'.
      We test the hypothesis that zoonotic pathogens are more likely to be associated
      with emerging diseases than non-emerging ones. Out of the emerging pathogens, 132
      (75%) are zoonotic, and overall, zoonotic pathogens are twice as likely to be
      associated with emerging diseases than non-zoonotic pathogens. However, the
      result varies among taxa, with protozoa and viruses particularly likely to
      emerge, and helminths particularly unlikely to do so, irrespective of their
      zoonotic status. No association between transmission route and emergence was
      found. This study represents the first quantitative analysis identifying risk
      factors for human disease emergence.

PMID- 11516377
TI  - Diseases of humans and their domestic mammals: pathogen characteristics, host
      range and the risk of emergence.
AB  - Pathogens that can be transmitted between different host species are of
      fundamental interest and importance from public health, conservation and economic
      perspectives, yet systematic quantification of these pathogens is lacking. Here,
      pathogen characteristics, host range and risk factors determining disease
      emergence were analysed by constructing a database of disease-causing pathogens
      of humans and domestic mammals. The database consisted of 1415 pathogens causing
      disease in humans, 616 in livestock and 374 in domestic carnivores. Multihost
      pathogens were very prevalent among human pathogens (61.6%) and even more so
      among domestic mammal pathogens (livestock 77.3%, carnivores 90.0%). Pathogens
      able to infect human, domestic and wildlife hosts contained a similar proportion
      of disease-causing pathogens for all three host groups. One hundred and ninety
      six pathogens were associated with emerging diseases, 175 in humans, 29 in
      livestock and 12 in domestic carnivores. Across all these groups, helminths and
      fungi were relatively unlikely to emerge whereas viruses, particularly RNA
      viruses, were highly likely to emerge. The ability of a pathogen to infect
      multiple hosts, particularly hosts in other taxonomic orders or wildlife, were
      also risk factors for emergence in human and livestock pathogens. There is
      clearly a need to understand the dynamics of infectious diseases in complex
      multihost communities in order to mitigate disease threats to public health,
      livestock economies and wildlife.

PMID- 11516378
TI  - Emerging infectious pathogens of wildlife.
AB  - The first part of this paper surveys emerging pathogens of wildlife recorded on
      the ProMED Web site for a 2-year period between 1998 and 2000. The majority of
      pathogens recorded as causing disease outbreaks in wildlife were viral in origin.
      Anthropogenic activities caused the outbreaks in a significant majority of cases.
      The second part of the paper develops some matrix models for quantifying the
      basic reproductive number, R(0), for a variety of potential types of emergent
      pathogen that cause outbreaks in wildlife. These analyses emphasize the
      sensitivity of R(0) to heterogeneities created by either the spatial structure of
      the host population, or the ability of the pathogens to utilize multiple host
      species. At each stage we illustrate how the approach provides insight into the
      initial dynamics of emergent pathogens such as canine parvovirus, Lyme disease,
      and West Nile virus in the United States.

PMID- 11516379
TI  - Reconstructing the origins of human hepatitis viruses.
AB  - Infections with hepatitis B and C viruses (HBV, HCV) are widespread in human
      populations throughout the world, and are major causes of chronic liver disease
      and liver cancer. HBV, HCV and the related hepatitis G virus or GB virus C
      (referred to here as HGV/GBV-C) are capable of establishing persistent,
      frequently lifelong infections characterized by high levels of continuous
      replication. All three viruses show substantial genetic heterogeneity, which has
      allowed each to be classified into a number of distinct genotypes that have
      different geographical distributions and associations with different risk groups
      for infection. Information on their past transmission and epidemiology might be
      obtained by estimation of the time of divergence of the different genotypes of
      HCV, HBV and HGV/GBV-C using knowledge of their rates of sequence change. While
      information on the latter is limited to short observation periods and is
      therefore subject to considerable error and uncertainty, the relatively recent
      times of origin for genotype of each virus predicted by this method (HCV, 500
      2000 years; HBV, 3000 years; HGV/GBV-C, 200 years) are quite incompatible with
      their epidemiological distributions in human populations. They also cannot easily
      be reconciled with the recent evidence for species-associated variants of HBV and
      HGV/GBV-C in a range of non-human primates. The apparent conservatism of viruses
      over long periods implied by their epidemiological distributions instead suggests
      that nucleotide sequence change may be subject to constraints peculiar to viruses
      with single-stranded genomes, or with overlapping reading frames that defy
      attempts to reconstruct evolution according to the principles of the 'molecular
      clock'. Large population sizes and intense selection pressures that optimize
      fitness may be additional factors that set virus evolution apart from that of
      their hosts.

PMID- 11516380
TI  - Acquisition of virulence-associated factors by the enteric pathogens Escherichia
      coli and Salmonella enterica.
AB  - In this review we summarize recent genomic studies that shed light on the
      mechanism through which pathogenic Escherichia coli and Salmonella enterica have
      evolved. We show how acquisition of DNA at specific sites on the chromosome has
      contributed to increased genetic variation and virulence of these two genera of
      the Enterobacteriaceae.

PMID- 11516381
TI  - The population genetics of Trypanosoma brucei and the origin of human
      infectivity.
AB  - The African trypanosome, Trypanosoma brucei, is a zoonotic parasite transmitted
      by tsetse flies. Two of the three subspecies, T. brucei gambiense and T.b.
      rhodesiense, cause sleeping sickness in humans whereas the third subspecies, T.b.
      brucei, is not infective to humans. We propose that the key to understanding
      genetic relationships within this species is the analysis of gene flow to
      determine the importance of genetic exchange within populations and the
      relatedness of populations. T.brucei parasites undergo genetic exchange when
      present in infections of mixed genotypes in tsetse flies in the laboratory,
      although this is not an obligatory process. Infections of mixed genotype are
      surprisingly common in field isolates from tsetse flies such that there is
      opportunity for genetic exchange to occur. Population genetic analyses, taking
      into account geographical and host species of origin, show that genetic exchange
      occurs sufficiently frequently in the field to be an important determinant of
      genetic diversity, except where particular clones have acquired the ability to
      infect humans. Thus, T. brucei populations have an 'epidemic' genetic structure,
      but the better-characterized human-infective populations have a 'clonal'
      structure. Remarkably, the ability to infect humans appears to have arisen on
      multiple occasions in different geographical locations in sub-Saharan Africa. Our
      data indicate that the classical subspecies terminology for T. brucei is
      genetically inappropriate. It is an implicit assumption in most infectious
      disease biology that when a zoonotic pathogen acquires the capability to infect
      humans, it does so once and then spreads through the human population from that
      single-source event. For at least one major pathogen in tropical medicine, T.
      brucei, this assumption is invalid.

PMID- 11516382
TI  - The shifting landscape of tick-borne zoonoses: tick-borne encephalitis and Lyme
      borreliosis in Europe.
AB  - The two major vector-borne diseases of northern temperate regions, tick-borne
      encephalitis (TBE) and Lyme borreliosis (LB), show very different epidemiological
      patterns, but both have increased significantly in incidence since the 1980s.
      Insight into the temporal dynamics of TBE, gained from statistical analysis of
      spatial patterns integrated with biological explanation, suggests that the recent
      increases in TBE cases in Central Europe and the Baltic States may have arisen
      largely from changes in human behaviour that have brought more people into
      contact with infected ticks. Under forecast climate change scenarios, it is
      predicted that enzootic cycles of TBE virus may not survive along the southern
      edge of their present range, e.g. in Slovenia, Croatia and Hungary, where case
      numbers are indeed decreasing. New foci, however, are predicted and have been
      observed in Scandinavia. At the same time, human impact on the landscape,
      increasing both the habitat and wildlife hosts of ticks, has allowed tick
      populations to multiply significantly. This probably accounts for a genuine
      emergence of LB, with its high potential transmission rate, in both the USA and
      Europe, although the rate of emergence has been exaggerated by improved
      surveillance and diagnosis.

PMID- 11516383
TI  - Early effects of climate change: do they include changes in vector-borne disease?
AB  - The world's climate appears now to be changing at an unprecedented rate. Shifts
      in the distribution and behaviour of insect and bird species indicate that
      biological systems are already responding to this change. It is well established
      that climate is an important determinant of the spatial and temporal distribution
      of vectors and pathogens. In theory, a change in climate would be expected to
      cause changes in the geographical range, seasonality (intra-annual variability),
      and in the incidence rate (with or without changes in geographical or seasonal
      patterns). The detection and then attribution of such changes to climate change
      is an emerging task for scientists. We discuss the evidence required to attribute
      changes in disease and vectors to the early effects of anthropogenic climate
      change. The literature to date indicates that there is a lack of strong evidence
      of the impact of climate change on vector-borne diseases (i.e. malaria, dengue,
      leishmaniasis, tick-borne diseases). New approaches to monitoring, such as
      frequent and long-term sampling along transects to monitor the full latitudinal
      and altitudinal range of specific vector species, are necessary in order to
      provide convincing direct evidence of climate change effects. There is a need to
      reassess the appropriate levels of evidence, including dealing with the
      uncertainties attached to detecting the health impacts of global change.

PMID- 11516384
TI  - The resurgence of tuberculosis in Russia.
AB  - This paper documents and attempts to explain the epidemic spread of tuberculosis
      (TB) in Russia during the 1990s. After several decades of decline, the
      notification rate of all new TB cases among permanent residents increased by 7.5%
      per year from 1991-1999 and the death rate by 11% per year. Growth was quickest
      from 1993-1995 but increased again after the economic crisis of August 1998.
      Approximately 120 000 new cases and 30 000 deaths were reported in 1999. Case
      detection and cure rates have fallen in Russia since the mid-1980s; the fall has
      been accompanied by a higher frequency of severe disease among cases, and higher
      death and case fatality rates. With a mathematical model describing the
      deterioration in case finding and cure rates we could replicate the average rate
      of increase in incidence 1991-1999 but not the precise timing of the observed
      changes. Other factors that probably helped to shape the observed rise in
      caseload include enhanced transmission due to the mixing of prison and civilian
      populations, an increase in susceptibility to disease, and changes in the
      proportion of cases detected by surveillance. Although our explanation for the
      resurgence of TB is incomplete, we have identified a set of measures that can be
      implemented now to cut transmission, incidence and deaths.

PMID- 11516385
TI  - The epidemiology of human immunodeficiency virus in South Africa.
AB  - We review the epidemiology of human immunodeficiency virus (HIV) in South Africa
      where the prevalence of HIV infection is among the highest in the world. The
      epidemic reached South Africa relatively recently but the prevalence of infection
      has increased rapidly and there are significant differences among provinces.
      Although few 15-year-old people are infected the prevalence increases rapidly
      with age thereafter, especially among women. The prevalence of herpes simplex
      virus type 2 exceeds that of HIV and curable sexually transmitted infections are
      common. 'Circular migration' may help to explain the high rates and rapid spread
      of HIV in the region. The incidence of tuberculosis has increased dramatically as
      a result of the HIV epidemic. Antiretroviral therapy for the prevention of
      vertical transmission has been shown to be effective in local conditions but
      transmission through breast-feeding remains problematical. While some
      epidemiological models have been developed, much more needs to be done in this
      regard in order to plan, coordinate and evaluate an effective response to the
      epidemic. We conclude by discussing some of the research that is needed and steps
      that could be taken to reduce the continued spread of the infection.

PMID- 11516386
TI  - The emergence of rabbit haemorrhagic disease virus: will a non-pathogenic strain
      protect the UK?
AB  - Rabbit haemorrhagic disease virus emerged in China in 1984, and has killed
      hundreds of millions of wild rabbits in Australia and Europe. In the UK there
      appears to be an endemic non-pathogenic strain, with high levels of
      seroprevalence being recorded, in the absence of associated mortality. Using a
      seasonal, age-structured model we examine the hypothesis that differences in
      rabbit population demography differentially affect the basic reproductive rates
      (R(0)) of the pathogenic and non-pathogenic strains, leading to each dominating
      in some populations and not others. The strain with the higher R(0) excluded the
      other, with the dynamics depending upon the ratio of the two R(0) values. When
      the non-pathogenic strain dominated, the pathogenic strain caused only transient
      mortality, although this could be significant when the two R(0) values were
      similar. When the pathogenic strain dominated, repeated epidemics led to host
      eradication. Seroprevalence data suggest that the non-pathogenic strain may be
      protecting some, but not all UK populations, with half being 'at risk' from
      invasion by the pathogenic strain and a fifth prone to significant transient
      mortality. We identify key questions for empirical research to test this
      prediction.

PMID- 11516387
TI  - Monitoring and surveillance for rare health-related events: a review from the
      veterinary perspective.
AB  - Disease monitoring and surveillance systems (MOSSs) have become one of the major
      components of veterinary activity. Such systems are used to assess the existing
      levels of prevalence, the effectiveness of control programmes and, after disease
      eradication, to document the continued absence of disease from a given region or
      zone. With decreasing disease or infection prevalence, traditional approaches
      become less reliable and increasingly costly. The objective of this work was to
      summarize and discuss methodological issues related to veterinary (animal health)
      MOSSs. There are considerable inconsistencies in the use of the terms
      'monitoring' and 'surveillance'. Passive as well as active MOSS have their
      disadvantages when used for rare health-related events such as emerging and re
      emerging diseases. There is a need for evaluation and improvement of these
      approaches. Integrated systems that call for the use of several parallel
      surveillance activities seem to be the favoured approach, and analytical methods
      to combine MOSS data from various sources into a population prevalence, or
      probability of disease freedom, are under development. The health and safety of
      the animal and human generations depends on our continuous ability to detect,
      monitor and control newly emerging or re-emerging livestock diseases and zoonoses
      rapidly. Uniform surveillance definitions, sound scientifically based approaches
      that use the resources and data available, and a pool of researchers and
      veterinary public health officials with sufficient training in epidemiology, are
      critically important to handle this challenging task.

PMID- 11516389
TI  - REST acts through multiple deacetylase complexes.
AB  - The RE1 binding silencer protein REST represses neuronal-specific gene expression
      in nonneuronal cell types. In this issue of Neuron, Ballas et al. show that REST
      inhibits gene expression via the recruitment of multiple histone deacetylase
      complexes.

PMID- 11516390
TI  - Seeing is believing: GFP transgenics illuminate synapse elimination.
AB  - Synapses are lost during developmental synapse elimination. Until now, it has
      been impossible to follow elimination in the entirety of any neuron's branches
      and synapses. Using transgenic mice in which one or two of a muscle's motoneurons
      express variants of GFP, Keller-Peck et al. show in this issue of Neuron that
      elimination occurs asynchronously by local competitive interactions at each
      synaptic site, apparently independent of events elsewhere in the neuron's
      terminal field.

PMID- 11516391
TI  - Electrical wiring of the oscillating brain.
AB  - In this issue of Neuron, two laboratories (Deans et al. and Hormuzdi et al.) find
      that cortical gamma oscillation in vitro is impaired in the Cx36 knockout mouse.
      What are the implications?

PMID- 11516392
TI  - A route for prion neuroinvasion.
AB  - The astonishing recognition that self-propagating changes in protein structure
      may be at the basis of spongiform encephalopathies is changing our views of
      transmissible diseases. Infectious agents consisting of abnormally folded
      proteins (i.e., the prion) can propagate in host organisms using previously
      unrecognized routes and invade the brain after a dangerous liaison with the
      immune system. The identification of the nodal points of neuroinvasion and new
      techniques to amplify minute amounts of misfolded proteins may open the
      possibility for post exposure prophylaxis.

PMID- 11516393
TI  - Synaptic plasticity and nicotine addiction.
AB  - Nicotine, the main addictive component of tobacco, activates and desensitizes
      nicotinic acetylcholine receptors (nAChRs). In that way, nicotine alters normal
      nicotinic cholinergic functions. Among the myriad of psychopharmacological
      effects that underlie the addiction process, nicotine influences nAChR
      participation in synaptic plasticity. This influence has particular importance in
      the mesocorticolimbic dopamine system, which serves during the reinforcement of
      rewarding behaviors.

PMID- 11516394
TI  - Regulation of neuronal traits by a novel transcriptional complex.
AB  - The transcriptional repressor, REST, helps restrict neuronal traits to neurons by
      blocking their expression in nonneuronal cells. To examine the repercussions of
      REST expression in neurons, we generated a neuronal cell line that expresses REST
      conditionally. REST expression inhibited differentiation by nerve growth factor,
      suppressing both sodium current and neurite growth. A novel corepressor complex,
      CoREST/HDAC2, was shown to be required for REST repression. In the presence of
      REST, the CoREST/HDAC2 complex occupied the native Nav1.2 sodium channel gene in
      chromatin. In neuronal cells that lack REST and express sodium channels, the
      corepressor complex was not present on the gene. Collectively, these studies
      define a novel HDAC complex that is recruited by the C-terminal repressor domain
      of REST to actively repress genes essential to the neuronal phenotype.

PMID- 11516395
TI  - Beta1-class integrins regulate the development of laminae and folia in the
      cerebral and cerebellar cortex.
AB  - Mice that lack all beta1-class integrins in neurons and glia die prematurely
      after birth with severe brain malformations. Cortical hemispheres and cerebellar
      folia fuse, and cortical laminae are perturbed. These defects result from
      disorganization of the cortical marginal zone, where beta1-class integrins
      regulate glial endfeet anchorage, meningeal basement membrane remodeling, and
      formation of the Cajal-Retzius cell layer. Surprisingly, beta1-class integrins
      are not essential for neuron-glia interactions and neuronal migration during
      corticogenesis. The phenotype of the beta1-deficient mice resembles pathological
      changes observed in human cortical dysplasias, suggesting that defective integrin
      mediated signal transduction contributes to the development of some of these
      diseases.

PMID- 11516396
TI  - Asynchronous synapse elimination in neonatal motor units: studies using GFP
      transgenic mice.
AB  - In developing muscle, synapse elimination reduces the number of motor axons that
      innervate each postsynaptic cell. This loss of connections is thought to be a
      consequence of axon branch trimming. However, branch retraction has not been
      observed directly, and many questions remain, such as: do all motor axons retract
      branches, are eliminated branches withdrawn synchronously, and are withdrawing
      branches localized to particular regions? To address these questions, we used
      transgenic mice that express fluorescent proteins in small subsets of motor
      axons, providing a unique opportunity to reconstruct complete axonal arbors and
      identify all the postsynaptic targets. We found that, during early postnatal
      development, each motor axon loses terminal branches, but retracting branches
      withdraw asynchronously and without obvious spatial bias, suggesting that local
      interactions at each neuromuscular junction regulate synapse elimination.

PMID- 11516397
TI  - Loss of correlated motor neuron activity during synaptic competition at
      developing neuromuscular synapses.
AB  - During late stages of neural development, synaptic circuitry is edited by neural
      activity. At neuromuscular synapses, the transition from multiple to single
      innervation is modulated by the relative pattern of activity among inputs
      competing for innervation of the same muscle fiber. While experimental
      perturbations of activity result in marked changes in the timing of neuromuscular
      synaptic competition, little is known about the patterns of activity present
      during normal development. Here, we report the temporal patterning of motor unit
      activity in the soleus muscle of awake, behaving neonatal mice, and that
      patterning is modulated by gap-junctional coupling. Our work suggests that
      neuromuscular synaptic competition is modulated by surprisingly low levels of
      activity and may be triggered by the disappearance of temporally correlated
      activity among inputs competing for innervation of the same muscle fiber.

PMID- 11516398
TI  - The CRE/CREB pathway is transiently expressed in thalamic circuit development and
      contributes to refinement of retinogeniculate axons.
AB  - The development of precise connections in the mammalian brain proceeds through
      refinement of initially diffuse patterns, a process that occurs largely within
      critical developmental windows. To elucidate the molecular pathways that
      orchestrate these early periods of circuit remodeling, we have examined the role
      of a calcium- and cAMP-regulated transcriptional pathway. We show that there is a
      window of CRE/CREB-mediated gene expression in the developing thalamus, which
      precedes neocortical expression. In the LGN, this wave of gene expression occurs
      prior to visual experience, but requires retinal function. Mutant mice with
      reduced CREB expression show loss of refinement of retinogeniculate projections.
      These results suggest an important role of the CRE/CREB transcriptional pathway
      in the coordination of experience-independent circuit remodeling during forebrain
      development.

PMID- 11516399
TI  - Drosophila CAPS is an essential gene that regulates dense-core vesicle release
      and synaptic vesicle fusion.
AB  - Calcium-activated protein for secretion (CAPS) is proposed to play an essential
      role in Ca2+-regulated dense-core vesicle exocytosis in vertebrate neuroendocrine
      cells. Here we report the cloning, mutation, and characterization of the
      Drosophila ortholog (dCAPS). Null dCAPS mutants display locomotory deficits and
      complete embryonic lethality. The mutant NMJ reveals a 50% loss in evoked
      glutamatergic transmission, and an accumulation of synaptic vesicles at active
      zones. Importantly, dCAPS mutants display a highly specific 3-fold accumulation
      of dense-core vesicles in synaptic terminals, which was not observed in mutants
      that completely arrest synaptic vesicle exocytosis. Targeted transgenic CAPS
      expression in identified motoneurons fails to rescue dCAPS neurotransmission
      defects, demonstrating a cell nonautonomous role in synaptic vesicle fusion. We
      conclude that dCAPS is required for dense-core vesicle release and that a dCAPS
      dependent mechanism modulates synaptic vesicle release at glutamatergic synapses.

PMID- 11516400
TI  - GRAB: a physiologic guanine nucleotide exchange factor for Rab3A, which interacts
      with inositol hexakisphosphate kinase.
AB  - Diphosphoinositol-pentakisphosphate (InsP7) and bis-diphosphoinositol
      tetrakisphosphate (InsP8) possess pyrophosphate bonds. InsP7 is formed from
      inositol hexakisphosphate (InsP6) by recently identified InsP6 kinases designated
      InsP6K1 and InsP6K2. We now report the identification, cloning, and
      characterization of a novel protein, GRAB (guanine nucleotide exchange factor for
      Rab3A), which interacts with both InsP6K1 and Rab3A, a Ras-like GTPase that
      regulates synaptic vesicle exocytosis. GRAB is a physiologic GEF (guanine
      nucleotide exchange factor) for Rab3A. Consistent with a role of Rab3A in
      synaptic vesicle exocytosis, GRAB regulates depolarization-induced release of
      dopamine from PC12 cells and nicotinic agonist-induced hGH release from bovine
      adrenal chromaffin cells. The association of InsP6K1 with GRAB fits with a role
      for InsP7 in vesicle exocytosis.

PMID- 11516401
TI  - Presynaptic specificity of endocannabinoid signaling in the hippocampus.
AB  - Endocannabinoids are retrograde messengers released by neurons to modulate the
      strength of their synaptic inputs. Endocannabinoids are thought to mediate the
      suppression of GABA release that follows depolarization of a hippocampal CA1
      pyramidal neuron-termed "depolarization-induced suppression of inhibition" (DSI).
      Here, we report that DSI is absent in mice which lack cannabinoid receptor-1
      (CB1). Pharmacological and kinetic evidence suggests that CB1 activation inhibits
      presynaptic Ca2+ channels through direct G protein inhibition. Paired recordings
      show that endocannabinoids selectively inhibit a subclass of synapses
      distinguished by their fast kinetics and large unitary conductance. Furthermore,
      cannabinoid-sensitive inputs are unusual among central nervous system synapses in
      that they use N- but not P/Q-type Ca2+ channels for neurotransmitter release.
      These results indicate that endocannabinoids are highly selective, rapid
      modulators of hippocampal inhibition.

PMID- 11516402
TI  - Presynaptic inhibition caused by retrograde signal from metabotropic glutamate to
      cannabinoid receptors.
AB  - We report a type of synaptic modulation that involves retrograde signaling from
      postsynaptic metabotropic glutamate receptors (mGluRs) to presynaptic cannabinoid
      receptors. Activation of mGluR subtype 1 (mGluR1) expressed in cerebellar
      Purkinje cells (PCs) reduced neurotransmitter release from excitatory climbing
      fibers. This required activation of G proteins but not Ca2+ elevation in
      postsynaptic PCs. This effect was occluded by a cannabinoid agonist and totally
      abolished by cannabinoid antagonists. Depolarization-induced Ca2+ transients in
      PCs also caused cannabinoid receptor-mediated presynaptic inhibition. Thus,
      endocannabinoid production in PCs can be initiated by two distinct stimuli.
      Activation of mGluR1 by repetitive stimulation of parallel fibers, the other
      excitatory input to PCs, caused transient cannabinoid receptor-mediated
      depression of climbing fiber input. Our data highlight a signaling mechanism
      whereby activation of postsynaptic mGluR retrogradely influences presynaptic
      functions via endocannabinoid system.

PMID- 11516403
TI  - Synchronous activity of inhibitory networks in neocortex requires electrical
      synapses containing connexin36.
AB  - Inhibitory interneurons often generate synchronous activity as an emergent
      property of their interconnections. To determine the role of electrical synapses
      in such activity, we constructed mice expressing histochemical reporters in place
      of the gap junction protein Cx36. Localization of the reporter with somatostatin
      and parvalbumin suggested that Cx36 was expressed largely by interneurons.
      Electrical synapses were common among cortical interneurons in controls but were
      nearly absent in knockouts. A metabotropic glutamate receptor agonist excited LTS
      interneurons, generating rhythmic inhibitory potentials in surrounding neurons of
      both wild-type and knockout animals. However, the synchrony of these rhythms was
      weaker and more spatially restricted in the knockout. We conclude that electrical
      synapses containing Cx36 are critical for the generation of widespread,
      synchronous inhibitory activity.

PMID- 11516404
TI  - Impaired electrical signaling disrupts gamma frequency oscillations in connexin
      36-deficient mice.
AB  - Neural processing occurs in parallel in distant cortical areas even for simple
      perceptual tasks. Associated cognitive binding is believed to occur through the
      interareal synchronization of rhythmic activity in the gamma (30-80 Hz) range.
      Such oscillations arise as an emergent property of the neuronal network and
      require conventional chemical neurotransmission. To test the potential role of
      gap junction-mediated electrical signaling in this network property, we generated
      mice lacking connexin 36, the major neuronal connexin. Here we show that the loss
      of this protein disrupts gamma frequency network oscillations in vitro but leaves
      high frequency (150 Hz) rhythms, which may involve gap junctions between
      principal cells (Schmitz et al., 2001), unaffected. Thus, specific connexins
      differentially deployed throughout cortical networks are likely to regulate
      different functional aspects of neuronal information processing in the mature
      brain.

PMID- 11516405
TI  - Context effects on the neural correlates of recognition memory: an
      electrophysiological study.
AB  - Event-related potentials (ERPs) were recorded during a recognition memory test
      for previously studied visual objects. Some studied objects were paired with the
      same context (landscape scenes) as at study, some were superimposed on a
      different studied context, and some were paired with new contexts. Unstudied
      objects were paired with either a studied or a new context. Three ERP memory
      effects were observed: an early effect elicited by all stimuli containing at
      least one studied component; a second effect elicited only by stimuli in which
      both object and context had been studied; and a third effect elicited by stimuli
      containing a studied object. Thus, test stimuli engaged three distinct kinds of
      memory-related neural activity which differed in their specificity for task
      relevant features.

PMID- 11516406
TI  - Projections from the arcuate/ventromedial region of the hypothalamus to the
      preoptic area and bed nucleus of stria terminalis in the brain of the ewe; lack
      of direct input to gonadotropin-releasing hormone neurons.
AB  - This study aimed to determine whether cells in the region of the arcuate and
      ventromedial hypothalamic nuclei (ARC/VMH) project to the gonadotropin-releasing
      hormone (GnRH) cells in the preoptic area (POA) and diagonal band of Broca (dbB)
      of the female sheep brain. An anterograde tracer, biotinylated dextran amine
      (BDA), was injected (70 nl) into the ARC/VMH (n=7) and the brains were perfused 3
      weeks later. BDA terminals were mainly found in the dbB, POA and bed nucleus of
      stria terminalis (BNST). In order to determine the extent of input to GnRH
      neurons, we performed immunocytochemistry on the same sections with a GnRH
      antibody and examined close association of GnRH-immunoreactive (GnRH-IR) neurons
      (cell bodies and proximal dendrites) with BDA terminals. Of 223 GnRH-IR neurons
      that were examined, only three (1.3%) had BDA terminals in close proximity.
      Neither was close proximity observed between BDA terminals and GnRH-IR fibres.
      Injection of BDA into the BNST (n=6) showed terminals in POA, but only one of 273
      GnRH-IR cells examined had BDA terminals in close proximity and no GnRH-IR fibres
      had BDA terminals in close proximity. Our results suggest that (1) although there
      are projections from the VMH/ARC to the dbB, POA and BNST, an interneuron or
      chain of interneurons is required for input to the GnRH neurones; (2) any input
      to GnRH neurons from the BNST involves at least one interneuron. The identity of
      these interneurons remains to be determined. Thus, input to the GnRH neurons from
      the estrogen receptor-rich area of ARC/VMH and from the BNST is not direct.

PMID- 11516407
TI  - Spatial learning induces neurotrophin receptor and synapsin I in the hippocampus.
AB  - We report that rats learning a spatial memory task in the Morris water maze show
      elevated expression of the signal transduction receptor for BDNF and the synaptic
      associated protein synapsin I in the hippocampus. Nuclease protection assays
      showed maximal levels of TrkB and synapsin I mRNAs in the hippocampus by the time
      that asymptotic learning performance had been reached (Day 6). Increases in
      synapsin I mRNA were matched by changes in synapsin I protein as revealed by
      western blot analysis. Synapsin I is a downstream effector for the BDNF tyrosine
      kinase cascade pathway which has important roles in synaptic remodeling and
      function. Therefore, parallel changes in TrkB and synapsin I mRNAs suggest a role
      of the BDNF system in synaptic function or adaptation. Levels of TrkB mRNA in the
      hippocampus were attenuated after learning acquisition (Day 20), but synapsin I
      mRNA was still elevated, suggesting that the BDNF system may participate in
      events secondary to learning, such as strengthening of neural circuits. TrkB and
      synapsin I mRNAs showed an increasing trend in the cerebellum of learning rats
      and no changes were observed in the caudal cerebral cortex. The selectivity of
      the changes in trkB and synapsin I, affecting the hippocampus, is in agreement
      with the role of this structure in processing of spatial information. Behavioral
      regulation of neurotrophins may provide a molecular basis for the enhanced
      cognitive function associated with active lifestyles, and guide development of
      strategies to promote neural healing after CNS injury or disease.

PMID- 11516408
TI  - Mechanisms of glucose transport at the blood-brain barrier: an in vitro study.
AB  - How the brain meets its continuous high metabolic demand in light of varying
      plasma glucose levels and a functional blood-brain barrier (BBB) is poorly
      understood. GLUT-1, found in high density at the BBB appears to maintain the
      continuous shuttling of glucose across the blood-brain barrier irrespective of
      the plasma concentration. We examined the process of glucose transport across a
      quasi-physiological in vitro blood-brain barrier model. Radiolabeled tracer
      permeability studies revealed a concentration ratio of abluminal to luminal
      glucose in this blood-brain barrier model of approximately 0.85. Under conditions
      where [glucose](lumen) was higher than [glucose](ablumen), influx of radiolabeled
      2-deoxyglucose from lumen to the abluminal compartment was approximately 35%
      higher than efflux from the abluminal side to the lumen. However, when
      compartmental [glucose] were maintained equal, a reversal of this trend was seen
      (approximately 19% higher efflux towards the lumen), favoring establishment of a
      luminal to abluminal concentration gradient. Immunocytochemical experiments
      revealed that in addition to segregation of GLUT-1 (luminal>abluminal), the
      intracellular enzyme hexokinase was also asymmetrically distributed
      (abluminal>luminal). We conclude that glucose transport at the CNS/blood
      interface appears to be dependent on and regulated by a serial chain of membrane
      bound and intracellular transporters and enzymes.

PMID- 11516409
TI  - Stimulus time-locked responses of motoneurons during forelimb fictive locomotion
      evoked by repetitive stimulation of the lateral funiculus.
AB  - In cat forelimb fictive locomotion evoked by repetitive stimulation of the upper
      cervical lateral funiculus, locomotor discharges consisted of activities time
      locked to each stimulus, which were rhythmically modulated. The stimulus time
      locked activities were investigated by intracellular recording from motoneurons.
      In both elbow flexor and extensor motoneurons, there observed stimulus time
      locked disynaptic EPSPs, trisynaptic IPSPs and polysynaptic EPSPs, all of which
      were rhythmically modulated with specific patterns. The disynaptic EPSPs of
      flexor motoneurons were facilitated in the flexor phase of locomotion, whereas
      those of extensor motoneurons were facilitated from the flexor phase to the
      flexor-to-extensor transition phase. Modulation depth was larger in flexor
      motoneurons. Trisynaptic IPSPs changed in amplitude in parallel with the
      disynaptic EPSPs of the antagonistic motoneurons. Late, polysynaptic EPSPs of
      both flexor and extensor motoneurons increased in amplitude along with
      corresponding nerve discharges. After lesions of the lateral funiculus at C6/C7,
      both the disynaptic EPSPs and trisynaptic IPSPs were abolished in the motoneurons
      located caudally to the lesions. However, only trisynaptic IPSPs were lost in the
      rostrally located motoneurons. Furthermore, the lesions disclosed that extensor
      motoneurons received another kind of stimulus time-locked EPSPs, trisynaptic
      EPSPs, which were transmitted through the ventral part of the spinal cord, and
      rhythmically facilitated in the extensor phase. Stimulus time-locked PSPs
      observed in this study may at least in part be evoked by last-order interneurons
      of the central pattern generator, which may be reciprocally organized.

PMID- 11516410
TI  - Effects of low intensity radiofrequency electromagnetic fields on electrical
      activity in rat hippocampal slices.
AB  - Slices of rat hippocampus were exposed to 700 MHz continuous wave radiofrequency
      (RF) fields (25.2-71.0 V m(-1), 5-15 min exposure) in a stripline waveguide. At
      low field intensities, the predominant effect on the electrically evoked field
      potential in CA1 was a potentiation of the amplitude of the population spike by
      up to 20%, but higher intensity fields could produce either increases or
      decreases of up to 120 and 80%, respectively, in the amplitude of the population
      spike. To eliminate the possibility of RF-induced artefacts due to the metal
      stimulating electrode, the effect of RF exposure on spontaneous epileptiform
      activity induced in CA3 by 4-aminopyridine (50-100 microM) was investigated.
      Exposure to RF fields (50.0 V m(-1)) reduced or abolished epileptiform bursting
      in 36% of slices tested. The maximum field intensity used in these experiments,
      71.0 V m(-1), was calculated to produce a specific absorption rate (SAR) of
      between 0.0016 and 0.0044 W kg(-1) in the slices. Measurements with a Luxtron
      fibreoptic probe confirmed that there was no detectable temperature change (+/-
      0.1 degrees C) during a 15 min exposure to this field intensity. Furthermore,
      imposed temperature changes of up to 1 degrees C failed to mimic the effects of
      RF exposure. These results suggest that low-intensity RF fields can modulate the
      excitability of hippocampal tissue in vitro in the absence of gross thermal
      effects. The changes in excitability may be consistent with reported behavioural
      effects of RF fields.

PMID- 11516411
TI  - Chorda tympani nerve stimulation evokes Fos expression in regionally limited
      neuron populations within the gustatory nucleus of the solitary tract.
AB  - The distribution of neurons in the rostral nucleus of the solitary tract (rNST)
      that respond to gustatory input from the anterior tongue was visualized by Fos
      protein immunohistochemistry following electrical stimulation of the chorda
      tympani (CT) nerve in rats. Maps of Fos-immunoreactive (Fos-ir) neurons were
      compared with the distribution of CT afferent terminal fields labeled by
      transganglionic transport of rhodamine-dextran in a separate group of animals.
      The primary concentration of Fos-ir neurons localized in register with the major
      terminal fields of CT afferent fibers, in the central third of the rostral 1.0 mm
      of the NST ipsilateral to the stimulated nerve. A similar correspondence in
      location and degree of labeling of Fos-ir neurons and afferent terminals was
      observed in the ipsilateral dorsal spinal trigeminal complex (Sp5) pars caudalis,
      near the obex, and the Sp5 pars oralis near the rostral pole of the rNST. Thus,
      the magnitude of Fos upregulation in brainstem targets of the CT nerve having
      chemosensory or nociceptive function, was proportional to the relative density of
      the CT afferent input. This correspondence, and the absence of labeling in
      neurons known to be one additional synapse away from the afferent input within
      gustatory or oral reflex pathways, suggests that the cell map obtained represents
      mainly neurons that are directly activated via primary afferent synapses from CT
      fibers. The availability of a method to histochemically identify a population of
      putative second-order taste neurons will facilitate analysis of the
      cellular/molecular properties of these neurons and of synaptic circuitry in the
      rNST.

PMID- 11516412
TI  - Vitamin D(3) attenuates 6-hydroxydopamine-induced neurotoxicity in rats.
AB  - Previous reports have demonstrated that exogeneous administration of glial cell
      line-derived neurotrophic factor (GDNF) reduces ventral mesencephalic (VM)
      dopaminergic (DA) neuron damage induced by 6-hydroxydopamine (6-OHDA) lesioning
      in rats. Recent studies have shown that 1,25-dihydroxyvitamin D(3) (D3) enhances
      endogenous GDNF expression in vitro and in vivo. The purpose of present study was
      to investigate if administration of D3 in vivo and in vitro would protect against
      6-OHDA-induced DA neuron injury. Adult male Sprague-Dawley rats were injected
      daily with D3 or with saline for 8 days and then lesioned unilaterally with 6
      OHDA into the medial forebrain bundle. Locomotor activity was measured using
      automated activity chambers. We found that unilateral 6-OHDA lesioning reduced
      locomotor activity in saline-pretreated animals. Pretreatment with D3 for 8 days
      significantly restored locomotor activity in the lesioned animals. All animals
      were sacrificed for neurochemical analysis 6 weeks after lesioning. We found that
      6-OHDA administration significantly reduced dopamine (DA), 3,4-dihydroxy
      phenylacetic acid (DOPAC) and homovanilic acid (HVA) levels in the substantia
      nigra (SN) on the lesioned side in the saline-treated rats. D3 pretreatment
      protected against 6-OHDA-mediated depletion of DA and its metabolites in SN.
      Using primary cultures obtained from the VM of rat embryos, we found that 6-OHDA
      or H(2)O(2) alone caused significant cell death. Pretreatment with D3 (10(-10) M)
      protected VM neurons against 6-OHDA- or H(2)O(2)-induced cell death in vitro.
      Taken together, our data indicate that D3 pretreatment attenuates the hypokinesia
      and DA neuronal toxicity induced by 6-OHDA. Since both H(2)O(2) and 6-OHDA may
      injure cells via free radical and reactive oxygen species, the neuroprotection
      seen here may operate via a reversal of such a toxic mechanism.

PMID- 11516413
TI  - Accumbens dopamine mechanisms in sucrose intake.
AB  - Extracellular levels of dopamine (DA) and monoamine metabolites were measured in
      the nucleus accumbens (NAcc) during sucrose licking using microdialysis in freely
      moving rats. The converse relationship also was tested. Using bilateral reverse
      microdialysis, D1 and D2 receptor antagonists (SCH23390, sulpiride) and the DA
      uptake blocker nomifensine were introduced into NAcc while measuring both
      ingestive behavior and neurochemistry. Licking of 0.3 M sucrose caused a 305% (+/
      69%) increase in NAcc DA compared with water intake. Reverse microdialysis of
      nomifensine at a dose that increased accumbens DA levels (1484+/-346%) led to an
      increase of sucrose intake (152.5+/-5.4%). Concurrent infusions of the D1 and D2
      blockers with nomifensine brought sucrose ingestion back near to control levels
      (114.8+/-3.7%). The higher dose of the D2 antagonist sulpiride also increased DA
      levels and sucrose intake. In contrast, the lower dose of the D2, and both doses
      of the D1 antagonist had no chemical or behavioral effects. These results showed
      release of NAcc DA in response to sucrose licking and the converse, an
      augmentation of the behavior by uptake blockade. The same data, however, failed
      to prove that tonic, local accumbens D1 and D2 receptor activity influenced this
      ingestive behavior.

PMID- 11516414
TI  - A stable prostacyclin analog enhances ectopic activity in rat sensory neurons
      following neuropathic injury.
AB  - Prostanoids sensitize sensory afferents during inflammation. However, their role
      in neuropathic pain is still unclear. We analyzed the actions of prostanoids, non
      selective (indomethacin) or selective (celecoxib and NS-398) cyclooxygenase-2
      (COX or COX-2) inhibitors, on the ectopic activity of dorsal root ganglia (DRG)
      and dorsal horn (DH) neurons in a model of neuropathic injury. Extracellular
      recordings of DRG and DH neurons and cardiovascular measurements were performed
      on anesthetized, paralyzed and artificially ventilated adult male Sprague-Dawley
      rats whose sciatic nerve had been transected. PGD(2), PGE(2), PGF(2alpha),
      carbaprostacyclin (cPGI(2); a stable prostacyclin analog), and carbocyclic
      thromboxane (cTXA(2)) were administered at cumulative doses (0.0001-5 mg/kg,
      i.p.) at 5 or 10 min intervals. Only cPGI(2) significantly increased the DRG and
      DH activity in a dose-dependent manner, with ED(50) values of 0.05 (0.01-0.96)
      and 0.69 (0.11-1.04) mg/kg, respectively. The other prostanoids did not
      significantly increase activity, although they reduced heart rate for up to 5 min
      following administration. Time course experiments with single doses of cPGI(2) (1
      mg/kg, i.v.) increased DH discharge rate 3-17 min after injection. Indomethacin
      (3 mg/kg, s.c.), but not celecoxib or NS-398 (both at 6 mg/kg, s.c.), reduced
      both DRG and DH activity. Our results indicate that cPGI(2) excites DRG and DH
      neurons of neuropathic rats, and may suggest a role for IP prostanoid receptors
      in pain episodes associated with nerve injury. The inhibitory effect of
      indomethacin, but not celecoxib or NS-398, on ectopic activity may suggest that a
      tonic generation of PGI(2) by COX-1 could contribute to neuropathic pain.

PMID- 11516415
TI  - Subthalamic nucleus lesions reduce low frequency oscillatory firing of substantia
      nigra pars reticulata neurons in a rat model of Parkinson's disease.
AB  - Single unit recordings performed in animal models of Parkinson's disease revealed
      that output nuclei neurons display modifications in firing pattern and firing
      rate, which are supposed to give rise to the clinical manifestations of the
      illness. We examined the activity pattern of single units from the substantia
      nigra pars reticulata, the main output nuclei of the rodent basal ganglia, in
      urethane-anesthetized control and 6-hydroxydopamine-lesioned rats (a widespread
      model of Parkinson's disease). We further studied the effect of a subthalamic
      nucleus lesion in both experimental groups. Subthalamic nucleus lesion produces
      behavioral improvement in animal models of Parkinson's disease, and was expected
      to reverse the changes induced by 6-hydroxydopamine lesions. A meticulous
      statistical investigation, which included a non-biased classification of the
      recorded units by means of cluster analysis, allowed us to identify a low
      frequency oscillation of firing rate ( approximately 0.9 Hz) occurring in
      approximately 35% of the units recorded from 6-hydroxydopamine-lesioned rats, as
      the main feature differentiating 6-hydroxydopamine-lesioned and control rats.
      Subthalamic nucleus lesions significantly reduced the proportion of oscillatory
      units in 6-hydroxydopamine-lesioned rats. However, the population of nigral units
      recorded from rats bearing both lesions still differed significantly from control
      units. These results suggest that oscillatory activity in the basal ganglia
      output nuclei may be related to some clinical features of parkinsonism, and
      suggest a putative mechanism through which therapeutic interventions aimed at
      modifying subthalamic nucleus function produce clinical benefit in Parkinson's
      disease.

PMID- 11516416
TI  - Differential alteration of NMDA receptor subunits in the gerbil dentate gyrus and
      subiculum following seizure.
AB  - In the present study, a chronological and comparative analysis of the
      immunoreactivities of N-methyl-D-aspartate (NMDA) receptor subunits in
      hippocampus of both seizure resistant (SR) and seizure sensitive (SS) gerbils was
      made in order to clarify the temporal and spatial alterations of NMDA receptor
      subunit expressions in the hippocampus complex. The changes in NMDA receptor
      immunoreactivity in the hippocampi of SS gerbils were restricted to both the
      dentate gyrus and the subiculum. At 30 min postictal, a decline in NMDA receptor
      subunit 1 (NR1) immunoreactivity in the suprablade of dentate gyrus was observed.
      This is in contrast to the enhancement of its immunodensity in the infrablade. At
      3 h postictal the NR1 immunoreactivity in the infrablade also declined
      significantly. At 12 h postictal, its immunoreactivity in the hilar neurons was
      reduced. The NMDA receptor subunit 2A/B (NR2A/B) immunoreactivity did not alter
      until 12 h following seizure-onset, when it was slightly decreased in the granule
      cells and hilar neurons. In the subiculum, NR1 immunoreactivity was significantly
      decreased, and was almost undetectable in this region until 12 h postictal; in
      contrast the NR2A/B immunoreactivity in this region increased significantly in
      this time point. These results suggest that the altering NMDA receptor expression
      in both the dentate gyrus and subiculum may affect tissue excitability and have
      an important role in regulating seizure activity in SS gerbils.

PMID- 11516417
TI  - Intraspinal amino acid neurotransmitter activities are involved in the generation
      of rhythmic sympathetic nerve discharge in newborn rat spinal cord.
AB  - Endogenous neurotransmitter activities underlying the sympathetic nerve discharge
      (SND) generated by newborn rat spinal cord in vitro were investigated using
      glutamatergic, glycinergic, and GABAergic antagonists. Under control conditions,
      the SND power spectrum had two major frequency components: synchronous bursting
      SND (bSND) with power dominant at < 0.1 Hz and quasiperiodic SND (qSND)
      oscillating at 1-2 Hz. Using high Mg2+ solution (12-24 mM) to block Ca2+
      dependent synaptic transmission reversibly abolished SND. An interruption of
      glutamatergic neurotransmission by CNQX (non-NMDA receptor blocker) or L-AP4
      (reducing the synaptic release of glutamate) failed to affect qSND, but
      consistently reduced bSND. Application of kynurenate, a broad-spectrum ionotropic
      glutamate receptor blocker, only caused an unstable SND but did not reduce SND.
      In contrast, strychnine (Stry, glycine receptor antagonist) consistently reduced
      qSND in a dose-dependent manner. Bicuculline (Bic, GABA(A) receptor antagonist)
      induced a synchronous bSND of irregular rhythm, which could be further
      regularized by adding Stry. Bic-induced bSND was reversibly abolished by CNQX or
      L-AP4. In conclusion, intraspinal glycinergic, GABAergic, and glutamatergic
      activities are involved in the generation of the spinal cord-derived SND in
      newborn rats. Intraspinal GABAergic interneurons may tonically inhibit the
      glutamatergic bursting neurons that generate a synchronous bSND. Activities of
      these glutamatergic bursting neurons may also be modulated by intraspinal
      glycinergic interneurons.

PMID- 11516419
TI  - A-fibres sprouting from lamina I into lamina II of spinal dorsal horn after
      peripheral nerve injury in rats.
AB  - We have examined the labeling pattern in the spinal dorsal horn by an intra
      sciatic nerve injection of cholera toxin B subunit conjugated horseradish
      peroxidase (HRP) after transection of the posterior cutaneous nerve and inferior
      gluteal nerve, and found that the cholera toxin B subunit conjugated HRP labeling
      in lamina I was expanding into lamina II and there was a shrinking gap between
      lamina I and lamina III. This result suggests that A-fibre sprouting arise after
      peripheral nerve injury, but mainly from small calibre Adelta-fibres which
      terminate in lamina I.

PMID- 11516418
TI  - Topically applied clonidine protects the rat retina from ischaemia/reperfusion by
      stimulating alpha(2)-adrenoceptors and not by an action on imidazoline receptors.
AB  - Ischaemia was induced to the rat retina by raising the intraocular pressure above
      the systolic blood pressure for 45 min. After a reperfusion period of 5 days,
      alterations in the localisation of choline acetyltransferase (ChAT) and
      calretinin immunoreactivities, a reduction in the thickness of the inner retinal
      layers and a decline in the b-wave amplitude of the electroretinogram were
      recorded. These changes were blunted when clonidine was injected
      intraperitoneally before or after ischaemia or when applied topically by a
      specific regime. Other alpha(2)-adrenoceptor agonists, brimonidine and
      apraclonidine, acted in a similar way to clonidine when applied topically but
      because of the number of experiments carried out a comparison between the
      effectiveness of the different alpha(2)-adrenoceptor agonists was not possible.
      The protective effect of clonidine was attenuated when the alpha(2)-adrenoceptor
      antagonists yohimbine or rauwolscine were co-administered, suggesting that the
      mechanism of action of the drug is to stimulate alpha(2)-adrenoceptors. In
      addition, the imidazoline receptor ligands, BU-226 and AGN-192403 did not blunt
      the effect of ischaemia/reperfusion, supporting the notion that the protective
      action of the alpha(2)-adrenoceptor agonists does not involve imidazoline sites
      but rather the activation of alpha(2)-adrenoceptors. The protective effect of
      0.5% clonidine appeared to be greater when topically applied to the eye that
      received ischaemia than when applied by the same regime to the contralateral eye.
      These studies suggest that while most of topically applied clonidine reaches the
      retina by a systemic route one cannot rule out additional pathways.

PMID- 11516420
TI  - Behavioral, electrophysiological, and histopathological consequences of mild
      fluid-percussion injury in the rat.
AB  - Metabolic dysfunction in the relay nuclei of the rat vibrissa circuit follows
      traumatic brain injury (TBI). This study examined the effects of mild (1.4-1.5
      atm) parasagittal fluid-percussion injury on the electrophysiology of this
      circuit. TBI caused significant reductions in slope and increases in latency of
      vibrissa-evoked field potentials 3 days after injury. Assessment of open-field
      swimming revealed an increase in thigmotaxis 2 days after injury. TBI caused mild
      selective cortical damage and limited axonal swelling at the injury site. Thus
      mild injury disrupts somatosensory electrophysiology and exploratory behavior.

PMID- 11516421
TI  - Postnatal stress selectively upregulates striatal N-methyl-D-aspartate receptors
      in male rats.
AB  - Early life events have been thought to contribute towards vulnerability to drug
      addiction later in life. In the present investigation, the effect of daily
      neonatal maternal isolation stress on NMDA channel activity was studied. [3H]MK
      801 binding was measured in several brain regions from neonatally isolated (ISO)
      and nonhandled (NH) adult male and female rats. Maximal [3H]MK-801 binding in the
      caudate-putamen of male ISO rats was 58% higher compared to same sex NH rats.
      Unlike male rats, maximal [3H]MK-801 binding in the caudate-putamen of female ISO
      rats was lower than female NH rats. No other brain region showed any significant
      difference in maximal [3H]MK-801 binding between ISO and NH male and female rats,
      respectively. There was no effect of pup isolation on the binding affinity (K(d)
      value) in either sex. Repeated maternal isolation is associated with alterations
      in the NMDA channel activity in the caudate-putamen of adult rats, and may be
      responsible for the augmentation in the addictive behavior reported.

PMID- 11516423
TI  - Effects of nociceptin on cardiac norepinephrine and acetylcholine release evoked
      by ouabain.
AB  - We investigated whether the novel peptide, nociceptin, modulates neuronal
      transmission at autonomic nerve endings. Using a cardiac dialysis technique, the
      effects of locally applied nociceptin on cardiac acetylcholine (ACh) and
      norepinephrine (NE) release were examined in anesthetized cats. Dialysis probes
      were implanted in the left ventricular wall, with the concentration of dialysate
      NE or ACh serving as an indicator of NE or ACh output at cardiac sympathetic or
      parasympathetic nerve endings. Locally applied ouabain evoked increases in NE and
      ACh output. Nociceptin suppressed the ouabain induced ACh increment. The ouabain
      induced NE release was not altered by nociceptin. However, in the presence of
      desipramine (a NE uptake inhibitor), nociceptin suppressed the ouabain-induced NE
      release. Inhibition by nociceptin of ouabain-induced release of NE or ACh was
      blocked by pretreatment with nocistatin (a nociceptin action blocking peptide).
      Nociceptin-induced inhibition of ACh or NE release is attributable to pre
      synaptic modulation rather than a reversal of the ouabain effect. These findings
      demonstrate that nociceptin inhibits cardiac autonomic neurotransmission via a
      presynaptic opioid receptor-like1(ORL1) receptor.

PMID- 11516422
TI  - Reversal of reserpine-induced vacuous chewing movements in rats by melatonin:
      involvement of peripheral benzodiazepine receptors.
AB  - Several reports have indicated that melatonin modulates striatal dopaminergic
      functions via its interaction with central and peripheral benzodiazepine (BZ)
      receptors. Clinical reports and animal studies speculated on the possible
      involvement of melatonin in the pathophysiology of tardive dyskinesia (TD). In
      view of this, the present experiment was performed to study the possible effect
      of melatonin in modulation of reserpine-induced dyskinesia. Melatonin (1-10
      mg/kg) dose dependently suppressed the severity of vacuous chewing movements
      (VCMs) in rats. Prior administration of the putative melatonin receptor
      antagonists luzindole (2.5 and 5 mg/kg) or prazosin (2.5 and 5 mg/kg) failed to
      antagonize melatonin (2.5 mg/kg) reversal of reserpine-induced VCMs. However, the
      peripheral BZ receptor antagonist PK11195 (0.5 and 1 mg/kg) but not flumazenil (1
      and 2 mg/kg), dose dependently antagonized melatonin's reversal of reserpine
      induced VCMs. Taken together the present results demonstrate that melatonin
      reverses reserpine-induced VCMs and that this could be due to enhancement of
      GABAergic activity via peripheral BZ receptors.

PMID- 11516424
TI  - Increases in mRNA levels for Talpha1-tubulin in the rat kindling model of
      epilepsy.
AB  - The expression of mRNA for Talpha1-tubulin, a cytoskeletal protein, was studied
      in the rat kindling model of epilepsy. The Talpha1-tubulin mRNA level increased
      significantly in the dentate gyrus (DG) and CA3 of hippocampus ipsilateral to
      stimulation from 8 h to 4 weeks after amygdaloid kindled seizures. The peak
      increase was observed at 1 week after the last seizures both in the DG and CA3.
      These results suggest that the microtubule formation contributes to synaptic
      remodeling and reorganization of neural networks, which may be based on the
      kindling-inducing epileptogenesity.

PMID- 11516425
TI  - Cholinergic neurons expressing substance P receptor (NK(1)) in the basal
      forebrain of the rat: a double immunocytochemical study.
AB  - Cholinergic neurons expressing substance P receptor (SPR, NK(1)) were examined in
      the rat brain using double immunofluorescence. The distribution of SPR-like
      immunoreactive (SPR-LI) neurons completely overlapped with that of choline
      acetyltransferase (ChAT)-LI neurons in the medial septal nucleus, the nucleus of
      diagonal band of Broca, the magnocellular preoptic nucleus, the substantia
      innominata of basal forebrain, the caudate-putamen, and the ventral pallidum of
      the basal ganglia. In the mesopontine tegmentum and the cranial motor nuclei of
      the brainstem, the distribution of SPR-LI and ChAT-LI neurons was partially
      overlapping. Neurons showing both SPR-like and ChAT-like immunoreactivities,
      however, were predominantly found above basal forebrain regions and 82-90% of
      these ChAT-LI neurons displayed SPR-like immunoreactivity, in addition to the
      confirmatory observation that 100% of the ChAT-LI neurons exhibit SPR-like
      immunoreactivity in the basal ganglia. In contrast, neurons double-labeled for
      SPR-like and ChAT-like immunoreactivities were hardly detected in aforementioned
      regions of the brainstem. The present study has provided morphological evidence
      for direct physiological modulation of cholinergic neurons by tachykinins through
      substance P receptor in the basal forebrain of the rat.

PMID- 11516426
TI  - Neuroprotective effects of lipoxygenase inhibitors against ischemic injury in rat
      hippocampal slice cultures.
AB  - Using organotypic cultures of rat hippocampal slices, we investigated the
      possible involvement of arachidonate cascades in neuronal death following
      ischemic insult. Oxygen/glucose deprivation-induced neuronal damage was
      efficiently attenuated by various inhibitors of lipoxygenase, whereas
      cyclooxygenase inhibitors were less effective. Interestingly, 5- and 12
      lipoxygenases are likely to separately mediate ischemic injury in the
      hippocampus. The present study will provide novel therapeutic targets for the
      development of neuroprotective agents.

PMID- 11516427
TI  - Lubeluzole attenuates K(+)-evoked extracellular accumulation of taurine in the
      striatum of healthy rats and rats with hepatic failure.
AB  - Lubeluzole is a newly designed neuroprotectant which has proved effective in the
      treatment of experimental stroke in rats, mainly by inhibition of the glutamate
      activated NO pathway, but also by counteracting osmotic stress by a mechanism
      associated with the release of the osmotically active amino acid taurine (Tau).
      Here we show that lubeluzole administered i.p. decreases by 25% the high (50 mM)
      K+-evoked accumulation of Tau in striatal microdialysates of healthy rats and by
      34% in rats with thioacetamide-induced hepatic failure, where the increased
      extracellular accumulation of Tau signifies ongoing hepatic encephalopathy.
      Lubeluzole does not affect the nonstimulated accumulation of Tau in either group
      of rats. The results indicate that lubeluzole may be effective in ameliorating
      ionic or osmotic stress in a range of pathological conditions involving the rise
      of extracellular K+, and also in decreasing the vulnerability to stress in rats
      with hepatic failure.

PMID- 11516428
TI  - Inhibition of caspase-3-like activity reduces glutamate induced cell death in
      adult rat retina.
AB  - Retinal cell death induced by over-stimulation of glutamate receptors is related
      to the programmed cell death or apoptosis. However, little is known about the
      intracellular events that lead to this cell death process in the retina. In this
      study, we asked if caspase-3 family cysteine proteases regulate cell death in an
      explant culture of adult rat retina after exposure to excessive glutamate. Cells
      with DNA fragmentation were first detected in the ganglion cell layer 3 h after a
      brief exposure to 20 mM glutamate; whilst those in the inner nuclear layer were
      first observed 6 h after the glutamate lesion. Caspase-3-like activity, as
      indicated by immunostaining of the fractin antibody that recognizes actin
      fragments generated by caspase-3 family proteases, was seen 40 min after
      glutamate treatment. Staining was first detected in the ganglion cell layer and
      then in the inner nuclear layer, preceding the appearance of cells with DNA
      fragmentation in these layers. Colocalization study showed that all cells with
      DNA breaks were fractin positive, indicating that caspase-3 family activity was
      involved in the glutamate-induced cell death in the adult rat retina.
      Furthermore, DEVD-CHO, a tetrapeptide inhibitor for caspase-3 family members,
      reduced dramatically the fractin staining and significantly alleviated glutamate
      induced cell death and DNA fragmentation in the ganglion cell layer and inner
      nuclear layer. Inhibitor for caspase-1-like activity, YVAD-CHO, neither reduced
      the fractin staining nor showed comparable neuroprotective effects to the retina.
      We conclude that glutamate-induced apoptotic cell death in adult rat retina is
      mediated by a specific activation of cysteine proteases related to the caspase-3
      family, and an intervention to the caspase-3 proteases provides effective
      protection to retinal neurons against glutamate excitotoxicity.

PMID- 11516429
TI  - The Ile164 beta(2)-adrenoceptor polymorphism alters salmeterol exosite binding
      and conventional agonist coupling to G(s).
AB  - beta(2)-adrenoceptors (beta(2)AR) are polymorphic at amino acid 164 (Thr or Ile)
      of the fourth transmembrane domain. In transfected fibroblasts, six agonists
      commonly used in the treatment of bronchospasm were studied. Isoproterenol,
      albuterol, metaproterenol, terbutaline, formoterol, and salmeterol displayed
      decreased binding affinities (K(i)s were 1.2-3.0-fold higher) and a significant
      degree of impaired maximal stimulation of adenylyl cyclase ( approximately 40%),
      was observed with all agonists for the Ile164 receptor. The ratios of signal
      transduction efficiencies (Tau function, Ile164/Thr164) varied from a low of 0.17
      for terbutaline to 0.49 for salmeterol. In addition, Ile164 bound salmeterol at
      the exosite, as delineated in perfusion washout studies, at a decreased level
      (31+/-4.8% vs. 49+/-4.4% retained salmeterol, respectively, P=0.02). In cAMP
      production studies under perfusion conditions, this decreased exosite binding
      caused a approximately 50% decrease in the duration of action of salmeterol at
      Ile164 (t(1/2)=21.0+/-3.6 vs. 46.8+/-4.1 min for Thr164, P=0.001). The durations
      of action for isoproterenol and formoterol under similar perfusion conditions
      were not different between the two receptors. These in vitro results indicate the
      Ile164 polymorphic receptor represents a pharmacogenetic locus for the most
      commonly utilized agonists in the treatment of asthma with a unique phenotype for
      salmeterol.

PMID- 11516430
TI  - Huperzine A attenuates cognitive dysfunction and neuronal degeneration caused by
      beta-amyloid protein-(1-40) in rat.
AB  - Huperzine A, a promising therapeutic agent for Alzheimer's disease, was examined
      for its potential to antagonize the deleterious neurochemical, structural, and
      cognitive effects of infusing beta-amyloid protein-(1-40) into the cerebral
      ventricles of rats. Daily intraperitoneal administration of huperzine A for 12
      consecutive days produced significant reversals of the beta-amyloid-induced
      deficit in learning a water maze task. This treatment also reduced the loss of
      choline acetyltransferase activity in cerebral cortex, and the neuronal
      degeneration induced by beta-amyloid protein-(1-40). In addition, huperzine A
      partly reversed the down-regulation of anti-apoptotic Bcl-2 and the up-regulation
      of pro-apoptotic Bax and P53 proteins and reduced the apoptosis that normally
      followed beta-amyloid injection. The present findings confirm that huperzine A
      can alleviate the cognitive dysfunction induced by intracerebroventricular
      infusion of beta-amyloid protein-(1-40) in rats. The beneficial effects are not
      confined to the cholinergic system, but also include favorable changes in the
      expression of apoptosis-related proteins and in the extent of apoptosis in
      widespread regions of the brain.

PMID- 11516431
TI  - B vitamins induce an antinociceptive effect in the acetic acid and formaldehyde
      models of nociception in mice.
AB  - The effect of some B vitamins in chemical and thermal models of nociception in
      mice was investigated. The association thiamine/pyridoxine/cyanocobalamin (TPC,
      20-200 mg/kg, i.p. or per os), thiamine, pyridoxine (50-200 mg/kg, i.p.) or
      riboflavin (3-100 mg/kg, i.p) induced an antinociceptive effect, not changed by
      naloxone (10 mg/kg, i.p.), in the acetic acid writhing model. Treatment for 7
      days with thiamine/pyridoxine/cyanocobalamin (100 or 200 mg/kg, i.p.), thiamine
      (50 or 100 mg/kg) or pyridoxine (50 or 100 mg/kg) or acute treatment with
      riboflavin (6 or 12 mg/kg, i.p) inhibited the nociceptive response induced by
      formaldehyde. The B vitamins did not inhibit the nociceptive response in the hot
      plate model. Both 7-day thiamine/pyridoxine/cyanocobalamin (100 mg/kg, i.p.) or
      acute riboflavin (25 or 50 mg/kg, i.p.) treatment partially reduced formaldehyde
      induced hindpaw oedema. The B vitamins antinociceptive effect may involve
      inhibition of the synthesis and/or action of inflammatory mediators since it was
      not observed in the hot-plate model, was not reversed by naloxone, only the
      second phase of the formaldehyde-induced nociceptive response was inhibited, and
      formaldehyde-induced hindpaw oedema was reduced.

PMID- 11516432
TI  - The AMPA receptor/Na(+) channel blocker BIIR 561 CL is protective in a model of
      global cerebral ischaemia.
AB  - In this study, we investigated whether the novel neuroprotective compound
      dimethyl-[2-[2-(3-phenyl-[1,2,4]oxadiazol-5-yl)-phenoxy]-ethyl]-amine
      hydrochloride, BIIR 561 CL, a combined non-competitive antagonist of AMPA
      receptors and blocker of voltage-gated Na+ channels, is protective in a rat model
      of severe global ischaemia. BIIR 561 CL administered immediately after 10 min of
      ischaemia (occlusion of both carotid arteries plus reduction of arterial blood
      pressure to 38-40 mm Hg) significantly reduced hippocampal damage at 4 x 26.8
      mg/kg (subcutaneous injections). The competitive AMPA receptor antagonist 2,3
      dihydro-6-nitro-7-sulfamoyl-benz(F)quinoxaline, NBQX, was used as a reference
      compound and was protective at 3x30 mg/kg (intraperitoneal and/or subcutaneous
      administration). BIIR 561 CL significantly reduced the ischaemia-induced
      premature mortality from 33.6% in the controls to 14.3%, whereas NBQX treatment
      had no statistically significant effect.Thus, BIIR 561 CL could be shown to
      reduce hippocampal damage and premature mortality in a model of severe global
      ischaemia. A compound with these properties might be an interesting candidate for
      the treatment of disorders related to global cerebral ischaemia in man.

PMID- 11516433
TI  - Interaction between 5-HT(1A) and 5-HT(1B) receptors: effects of 8-OH-DPAT-induced
      hypothermia in 5-HT(1B) receptor knockout mice.
AB  - To test for adaptive compensatory changes that may have occurred in the
      functional activity of somatodendritic 5-HT(1A) receptors during the development
      of constitutive "knockout" mice lacking the 5-HT(1B) receptor subtype (5-HT(1B) 
      /- KO), we assayed for decrease in body temperature induced by an acute
      subcutaneous injection of the 5-HT(1A) receptor agonist, 8-hydroxy 2(di-n
      propyl(amino)tetralin (8-OH-DPAT), either alone or in the presence of a selective
      5-HT(1A) receptor antagonist, N-[4-(2-methoxyphenyl)-1-piperazinyl]-N-(2
      pyridinyl) cyclo-hexanecarboxamide (WAY 100635). We compared dose-response
      curves, time course study, calculated ED(50) values (potency), maximal response
      to 8-OH-DPAT (efficacy) as well as measurements of the dose-dependent blockade of
      this response by WAY 100635 between wild-type controls and mutant mice. We found
      a higher efficacy of 8-OH-DPAT-induced hypothermia in 5-HT(1B) -/- KO compared to
      wild-type mice suggesting that an adaptive thermoregulatory process involving the
      functional activity of somatodendritic 5-HT(1A) receptors is altered in mutant
      mice lacking 5-HT(1B) receptors.

PMID- 11516434
TI  - SCH 58261 (an adenosine A(2A) receptor antagonist) reduces, only at low doses,
      K(+)-evoked glutamate release in the striatum.
AB  - The aim of the present work was to determine whether systemic administration of
      the adenosine A(2A) receptor antagonist, SCH 58261 (7-(2-phenylethyl)-5-amino-2
      (2-furyl)-pyrazolo-[4,3-e]-1,2,4,triazolo[1,5-c]pyrimidine), could modulate
      striatal glutamate outflow in the rat. Microdialysis experiments were performed
      in male Wistar rats implanted with microdialysis probes in the striatum.
      Pretreatment (15 min before) with SCH 58261 (0.01 and 0.1, but not 1 mg/kg
      intraperitoneally) significantly prevented K(+)-stimulated glutamate release.
      These results suggest that SCH 58261 could possess neuroprotective effects in the
      low dose range, while, at higher doses, the occurrence of additional mechanisms
      may limit the neuroprotective potential of this drug.

PMID- 11516435
TI  - (-)-1-(Benzofuran-2-yl)-2-propylaminopentane enhances locomotor activity in rats
      due to its ability to induce dopamine release.
AB  - "Catecholaminergic and serotoninergic activity enhancer" effects are newly found
      mechanisms of action of a class of compound that enhance impulse propagation
      mediated release of catecholamines and serotonin in the brain. In the present
      study, (-)-1-(benzofuran-2-yl)-2-propylaminopentane hydrochloride [(-)-BPAP HCl],
      a compound with selective and potent "catecholaminergic and serotoninergic
      activity enhancer" effects, was tested for its efficacy to potentiate locomotor
      activity in normal rats and to attenuate hypolocomotion in reserpine-treated
      rats. (-)-BPAP HCl potentiated locomotor activity in non-habituated rats during a
      2-h observation period dose-dependently (0.3-10 mg/kg). (-)-BPAP HCl (1-3 mg/kg)
      was also effective to reverse reserpine-induced hypolocomotion. The effects of (
      )-BPAP HCl in normal and reserpine-treated rats were attenuated by the dopamine
      D1 receptor antagonist, R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5
      tetrahydro-1H-3-benzazepine (SCH 23390), suggesting that the effects of (-)-BPAP
      HCl were mediated by activation of the dopaminergic system. In addition, the
      administration of (-)-BPAP HCl increased ipsilateral turning in unilaterally 6
      hydroxydopamine-lesioned rats, implying presynaptic activation of nigrostriatal
      dopaminergic terminals by (-)-BPAP HCl. Furthermore, although antiparkinsonian
      agents, such as apomorphine and amantadine, failed to improve reserpine-induced
      ptosis, (-)-BPAP HCl significantly improved ptosis. These findings suggested that
      a "catecholaminergic and serotoninergic activity enhancer" compound, (-)-BPAP,
      stimulates motor function in rats and improves motor deficits in animal models of
      Parkinson's disease due to its ability to induce dopamine release.

PMID- 11516436
TI  - p38 stress-activated protein kinase inhibitor reverses bradykinin B(1) receptor
      mediated component of inflammatory hyperalgesia.
AB  - The effects of a p38 stress-activated protein kinase inhibitor, 4-(4
      fluorophenyl)-2-(-4-methylsulfonylphenyl)-5-(4-pyridynyl) imidazole (SB203580),
      were evaluated in a rat model of inflammatory hyperalgesia. Oral, but not
      intrathecal, administration of SB203580 significantly reversed inflammatory
      mechanical hyperalgesia induced by injection of complete Freund's adjuvant into
      the hindpaw. SB203580 did not, however, affect the increased levels of
      interleukin-1beta and cyclo-oxygenase 2 protein observed in the hindpaw following
      complete Freund's adjuvant injection. Intraplantar injection of interleukin-1beta
      into the hindpaw elicited mechanical hyperalgesia in the ipsilateral paw, as well
      as in the contralateral paw, following intraplantar injection of the bradykinin
      B(1) receptor agonist des-Arg(9)-bradykinin. Oral administration of SB203580 1 h
      prior to interleukin-1beta administration prevented the development of
      hyperalgesia in the ipslateral paw and the contralateral bradykinin B(1) receptor
      mediated hyperalgesia. In addition, following interleukin-1beta injection into
      the ipsilateral paw, co-administration of SB203580 with des-Arg(9)-bradykinin
      into the contralateral paw inhibited the bradykinin B(1) receptor-mediated
      hyperalgesia. In human embryonic kidney 293 cells expressing the human bradykinin
      B(1) receptor, its agonist des-Arg(10)-kallidin produced a rapid phosphorylation
      of endogenous p38 stress-activated protein kinase. Our data suggest that p38
      stress-activated protein kinase is involved in the development of inflammatory
      hyperalgesia in the rat, and that its pro-inflammatory effects involve the
      induction of the bradykinin B(1) receptor as well as functioning as its
      downstream effector.

PMID- 11516437
TI  - Inhibition of inflammatory cell recruitment by the tachykinin NK(3)-receptor
      antagonist, SR 142801, in a murine model of asthma.
AB  - Several observations suggest that tachykinins (substance P, neurokinin A and
      neurokinin B) are involved in the pathogenesis of pulmonary diseases and elicit
      several airway responses such as bronchoconstriction and neurogenic inflammation
      via interactions with specific receptors denoted NK(1), NK(2) and NK(3). We have
      investigated the effect of a selective antagonist for tachykinin NK(3) receptor,
      SR 142801 ((R)-(N)-(1-(3-(1-benzoyl-3-(3,4-dichlorophenyl)piperidin-3-yl)propyl)
      4-phenylpiperidin-4-yl-N-methylacetamide), on the inflammatory cell recruitment
      in ovalbumin-sensitized and -challenged mice used as a model of allergic asthma.
      Twenty hours after the two-ovalbumin challenges, differential cell counts were
      calculated and indicated that SR 142801 caused a significant decrease in the
      number of neutrophils and eosinophils. Forty hours after the last ovalbumin
      exposure, SR 142801 induced a significant decrease in the recruitment of
      eosinophils. These results suggest that tachykinins and tachykinin NK(3)
      receptors can interfere with cell recruitment in inflammatory response.

PMID- 11516438
TI  - Influence of hypothyroid state on 45Ca(2+) influx and sensitivity of rat uterus
      to nifedipine and diltiazem.
AB  - The influence of methimazole-induced hypothyroidism on spontaneous rhythmic
      contractions and Ca2+ channel function of rat uterus was examined. Hypothyroidism
      significantly reduced the amplitude and frequency of spontaneous rhythmic
      contractions. Nifedipine (10(-12)-10(-6) M) and diltiazem (10(-9)-10(-4) M)
      caused concentration-related inhibition of the myogenic responses of the
      oestrogenised rat uterus obtained from both eu- and hypothyroid rats. However,
      nifedipine was less potent (IC(50); 5.4 x 10(-9) M; n=6) in hypothyroid rat
      uterus as compared to euthyroid controls (IC(50): 8.13 x 10(-12) M; n=9) to
      inhibit the rhythmic contractions. Similarly, diltiazem was less potent (IC(50):
      4.57 x 10(-6) M; n=9) to inhibit the uterine spontaneous contractions in
      hypothyroid than in euthyroid rat uterus (IC(50): 6.4 x 10(-8) M; n=6). A similar
      decrease in the sensitivity to nifedipine and diltiazem for reversal of K+ (100
      mM)-induced tonic contraction was observed in uterus obtained from hypothyroid
      rats compared to the controls. Both nifedipine and diltiazem were less potent for
      causing concentration-related inhibition of K+-stimulated 45Ca2+ influx in
      uterine strips taken from the hypothyroid rats. Thus, the IC(50) values of
      nifedipine (1.83 x 10(-8) M; n=12) and diltiazem (1.8 x 10(-6) M; n=9) were
      significantly greater in tissues obtained from hypothyroid rats compared to the
      controls (IC(50) of nifedipine, 1.15 x 10(-11) M; n=12, diltiazem, 8.1 x 10(-8)
      M; n=8). Nifedipine-sensitive influx of 45Ca2+ - stimulated either by K+ (100 mM)
      or Bay k8644 (1,4-dihydro-2,6-dimethyl-5-nitro-4-[2'-(trifluromethyl)phenyl]-3
      pyridine carboxylic acid methyl ester) (10(-8) M) was significantly less in
      uterine strips from hypothyroid rats compared to the controls. The results of the
      present study suggest that the inhibition of uterine rhythmic contractions may be
      attributable to a reduction in rat myometrial Ca2+ channel function in the
      hypothyroid state.

PMID- 11516439
TI  - Behavioral sensitization to heroin by cannabinoid pretreatment in the rat.
AB  - The behavioral consequences of acute heroin challenge (0.5 mg/kg, s.c.) were
      measured in rats previously submitted to repeated administration of increasing
      doses of the synthetic cannabinoid receptor agonist, R(+)-[2,3-dihydro-5-methyl-3
      [(morpholinyl)methyl]pyrrolo-[1,2,3-de]-1,4-benzoxazinyl]-(1-naphthalenyl)
      methanone mesylate (WIN55212.2) (first day 2 mg/kg, second day 4 mg/kg, third day
      8 mg/kg) or vehicle. Heroin administration to rats pretreated with vehicle
      produced catalepsy. The same dose of heroin in WIN55212.2-pretreated rats was
      followed by a marked increase of locomotor activity with stereotyped and non
      stereotyped behaviors. These effects were blocked by the opioid receptor
      antagonist, naloxone. These findings indicate that pretreatment with WIN55212.2
      produces cross-sensitization to heroin in the rat. These changes might reflect
      long-lasting changes of receptor population or transcriptional mechanisms in the
      mesolimbic system.

PMID- 11516440
TI  - Cognitive abilities in left-handers: writing posture revisited.
AB  - Among 1848 young men appearing before the Danish draft board, 232 (13%) were left
      handed. Of these, 118 (51%) used an inverted, or hook-like, writing posture, 49
      (21%) used a non-inverted posture and the remaining 65 (28%) could not be
      categorized. There were no differences between left- and right-handers on a
      battery of four cognitive tests. However, inverted left-handers performed
      significantly or near-significantly better than the non-inverted left-handers on
      two of the four tests and significantly better on the total score for the test
      battery. These results support the contention that the inverted posture is
      adaptive for left-handers and suggest that it may be more likely to be adopted by
      those with better cognitive abilities. Our findings conflict with earlier reports
      from two decades ago, however, and the association may therefore be socially and
      culturally dependent.

PMID- 11516441
TI  - Hemispatial differences in visually guided aiming are neither hemispatial nor
      visual.
AB  - Many studies have found differences in movements made to either side of the body
      midline. A popular interpretation of these differences has been that movements
      made by the arm, which is on same side of space in which the visual target
      appeared, are faster and better organised because they are processed within
      hemisphere. Carey et al. (Experimental Brain Research 112 (1996) 496) showed that
      hemispatial movement differences cannot be accounted for by such a model. Their
      data suggested that biomechanical factors such as those proposed by Gordon et al.
      (Experimental Brain Research 99 (1994) 112) could better account for differences
      in movement duration and several characteristics of velocity and acceleration.
      The present study examines these arguments by requiring subjects to make rapid
      pointing movements in two experiments. In the first, results demonstrated that
      hemispatial effects occurred in pointing movements made without any visual target
      or vision of the limb. These findings suggest that intra- and inter-hemispheric
      models are untenable. Gordon et al. argued that hand path direction relative to
      the long axis of the upper arm accounts for hemispatial effects on kinematics. In
      the second experiment hand path direction and hemispace were dissociated.
      Contralateral movements were performed more efficiently than ipsilateral
      movements, when target and starting positions required an adductive movement to
      acquire the contralateral target and an abductive movement to acquire the
      ipsilateral target. These results provide strong support for the Gordon et al.
      model, although the possible contributions of other dynamic factors and/or
      differential control of proximal and distal muscles by the central nervous system
      cannot be ruled out.

PMID- 11516442
TI  - Structural similarity causes different category-effects depending on task
      characteristics.
AB  - It has been suggested that category-specific impairments for natural objects may
      reflect that natural objects are more globally visually similar than artefacts
      and therefore more difficult to recognize following brain damage [Aphasiology 13
      (1992) 169]. This account has been challenged by the finding that the 'normal'
      disadvantage claimed for natural objects may be reversed when items from the
      categories of natural objects and artefacts are matched for visual complexity,
      familiarity and name frequency [Neuropsychologia 37 (1999) 1263]. In the
      experiments reported here it was investigated whether category effects could be
      found on object decision tasks (deciding whether pictures represented real
      objects or not), when the stimulus material was matched across categories. In
      experiment 1, a disadvantage for natural objects was found on difficult object
      decision tasks whereas no category difference was found on easy object decision
      tasks. In experiment 2 an advantage for natural objects was found during object
      decisions performed under degraded viewing conditions (lateralized stimulus
      presentation). It is argued that these findings can be accounted for by assuming
      that natural objects are more globally visually similar than artefacts, but that
      this difference between categories affects performance in different ways
      depending on task characteristics. Thus, the greater overlap between natural
      objects may be a disadvantage when the demand on perceptual differentiation is
      high (as it is in difficult object decision tasks). However, when viewing
      conditions are degraded and performance tends to depend on global shape
      information (carried by low spatial frequency components), natural objects may
      fare better than artefacts because the global shape of natural objects reveals
      more of their identity than the global shapes of artefacts.

PMID- 11516443
TI  - Functional neuroanatomy of three-term relational reasoning.
AB  - In a recent study we demonstrated that reasoning with categorical syllogisms
      engages two dissociable mechanisms. Reasoning involving concrete sentences
      engaged a left hemisphere linguistic system while formally identical arguments,
      involving abstract sentences, recruited a parietal spatial network. The
      involvement of a parietal visuo-spatial system in abstract syllogism reasoning
      raised the question whether argument forms involving explicit spatial relations
      (or relations that can be easily mapped onto spatial relations) are sufficient to
      engage the parietal system? We addressed this question in an event-related fMRI
      study of three-term relational reasoning, using sentences with concrete and
      abstract content. Our findings indicate that both concrete and abstract three
      term relational arguments activate a similar bilateral occipital-parietal-frontal
      network. However, the abstract reasoning condition engendered greater parietal
      activation than the concrete reasoning condition. We conclude that arguments
      involving relations that can be easily mapped onto explicit spatial relations
      engage a visuo-spatial system, irrespective of concrete or abstract content.

PMID- 11516444
TI  - Neural activity associated with episodic memory for emotional context.
AB  - To address the question of which brain regions subserve retrieval of emotionally
      valenced memories, we used event-related fMRI to index neural activity during the
      incidental retrieval of emotional and non-emotional contextual information. At
      study, emotionally neutral words were presented in the context of sentences that
      were either negatively, neutrally or positively valenced. At test, fMRI data were
      obtained while participants discriminated between studied and unstudied words.
      Recognition of words presented in emotionally negative relative to emotionally
      neutral contexts was associated with enhanced activity in right dorsolateral
      prefrontal cortex, left amygdala and hippocampus, right lingual gyrus and
      posterior cingulate cortex. Recognition of words from positive relative to
      neutral contexts was associated with increased activity in bilateral prefrontal
      and orbitofrontal cortices, and left anterior temporal lobe. These findings
      suggest that neural activity mediating episodic retrieval of contextual
      information and its subsequent processing is modulated by emotion in at least two
      ways. First, there is enhancement of activity in networks supporting episodic
      retrieval of neutral information. Second, regions known to be activated when
      emotional information is encountered in the environment are also active when
      emotional information is retrieved from memory.

PMID- 11516445
TI  - Human brain potential correlates of voice priming and voice recognition.
AB  - This study investigated repetition priming in the recognition of famous voices,
      recording reaction times (RTs) and event-related brain potentials (ERPs). In
      Experiment 1, a facilitation was found in RTs to famous but not to unfamiliar
      voices when these had been primed by a different voice sample of the same speaker
      earlier in the experiment. However, ERPs to both famous and unfamiliar voices
      showed repetition priming in terms of an increased P2 component, which is thought
      to be generated in the auditory cortex. When the likelihood of conscious
      retrieval of primes was reduced in Experiment 2, facilitatory priming in RTs was
      again observed for famous voices, but inhibitory priming was now observed for
      unfamiliar voices. This is consistent with predictions of a bias model of
      priming. Moreover, substantial priming was observed even when voice primes were
      backward speech samples, which were recognised at chance levels. The results
      suggests that (a) voice priming is mediated to a large extent by frequency
      characteristics of a particular voice, rather than by articulatory and other
      'sequential' features that are eliminated in backward speech; (b) priming affects
      the processing of voices in auditory cortical areas within 200 ms after voice
      onset; and (c) explicit recognition of a voice in the priming phase is not a
      necessary condition for priming to occur.

PMID- 11516446
TI  - Processing of irrelevant visual motion during performance of an auditory
      attention task.
AB  - The extent to which irrelevant perception of visual motion distractors can be
      modulated by manipulating auditory load in a relevant task was assessed with
      Positron Emission Tomography (PET) and behavioural experiments. Subjects
      performed an auditory task and ignored an irrelevant visual motion stimulus,
      under two conditions. In a low load condition, subjects were asked to detect
      words spoken in a loud voice among words spoken in a quiet voice, while in a high
      load condition they attempted to detect bisyllabic words among monosyllabic and
      trisyllabic words. We found that motion-related visual areas were strongly
      activated by the irrelevant motion stimulus, compared to a static stimulus, under
      both conditions of load in the auditory task. In a second behavioural experiment,
      the duration of the motion after-effect was similarly unaffected by adaptation
      under low or high auditory load. These results are in clear contrast with the
      strong modulation of irrelevant motion processing by visual load, as reflected in
      the duration of the motion after effect (Section 6) and neural responses in
      motion-related visual areas (Rees et al., Science, (1997) 278, 338). These
      findings support the claim that attentional capacity is restricted within but not
      between sensory modalities, and indicate that processing of visual distractors
      may occur whenever there is sufficient visual capacity to process them, despite
      being task- and modality-irrelevant.

PMID- 11516447
TI  - Memory-driven movements in limb apraxia: is there evidence for impaired
      communication between the dorsal and the ventral streams?
AB  - Memory-driven reaching and grasping movements were analysed in patients with left
      cerebral hemispheric damage and impaired gesture imitation. The dorsal and
      ventral streams of the visual pathway model of Milner and Goodale (Milner and
      Goodale, The Visual Brain in Action, 1995) are thought to operate relatively
      independently. However, cross-connections between the areas of each pathway are
      likely to enable interactions essential for higher-level praxis. Apraxic errors
      such as seen in gesture imitation can possibly be understood as arising from a
      disconnection of the two visual pathways. If the integrated action of the
      perceptual and visuomotor systems in patients with apraxia is compromised, then
      we would expect to find indications of impaired motor programming and misreaching
      in these patients when making movements driven by stored representations. Such a
      pattern, however, was not found in our sample of apraxic patients. Patients with
      limb apraxia produced normal movement kinematics and normal end-point accuracy
      when making memory-driven reaching movements with or without visual guidance of
      movement. Furthermore, perceptual information about object size and object
      distance were incorporated as normal in memory-driven grasping movements of these
      patients.

PMID- 11516448
TI  - Basal ganglia dysfunction, working memory, and sentence comprehension in patients
      with Parkinson's disease.
AB  - To investigate the role of the basal ganglia in working memory and sentence
      comprehension, 14 patients with Parkinson's disease (PD) were administered
      experimental measures of semantic and phonological working memory, and a measure
      of sentence comprehension, while receiving dopaminergic medications and after a
      period of withdrawal from these medications. An age- and education- matched
      control group (N=14) received the same measures. Comparison with control subjects
      revealed deficits in patients with PD in sentence processing regardless of
      medication status, but no deficits in working memory. In contrast to previous
      studies, withdrawal of dopaminergic medications had no significant impact on task
      related working memory functions or on sentence comprehension. Results suggest
      that basal ganglia dysfunction does not solely account for sentence comprehension
      deficits seen in PD.

PMID- 11516449
TI  - Continuous processing in macaque frontal cortex during visual search.
AB  - A central issue in mental chronometry is whether information is transferred
      between processing stages such as stimulus evaluation and response preparation in
      a continuous or discrete manner. We tested whether partial information about a
      stimulus influences the response stage by recording the activity of movement
      related neurons in the frontal eye field of macaque monkeys performing a
      conjunction visual search and a feature visual search with a singleton
      distractor. While movement-related neurons were activated maximally when the
      target of the search array was in their movement field, they were also activated
      for distractors even though a saccade was successfully made to the target outside
      the movement field. Most importantly, the level of activation depended on the
      properties of the distractor, with greater activation for distractors that shared
      a target feature or were the target during the previous session during
      conjunction search, and for the singleton distractor during feature search. These
      results support the model of continuous information processing and argue against
      a strictly discrete model.

PMID- 11516450
TI  - The eye movements of pure alexic patients during reading and nonreading tasks.
AB  - We compared the eye-movements of two patients who read letter-by-letter (LBL)
      following a left occipital lobe lesion with those of normal control subjects and
      of hemianopic patients in two tasks: a nonreading visual search task and a text
      reading task. Whereas the LBL readers exhibited similar eye-movement patterns to
      those of the other two groups on the nonreading task, their eye movements
      differed significantly during reading, as reflected in the disproportionate
      increase in the number and duration of fixations per word and in the regressive
      saccades per word. Importantly, relative to the two control groups, letter-by
      letter readers also made more fixations per word as word length increased,
      especially as word frequency and word imageability decreased. Two critical
      results emerged from these experiments: First, the alteration in the oculomotor
      behavior of the LBL readers during reading is similar to that seen in normal
      readers under difficult reading conditions, as well as in beginning readers and
      in those with developmental dyslexia, and appears to reflect difficulties in
      processing the visual stimulus. Second, the interaction of length with frequency
      and with imageability in determining the eye movement pattern is consistent with
      an interactive activation model of normal word recognition in which weakened
      activation of orthographic input can nevertheless engage high-level lexical
      factors.

PMID- 11516451
TI  - Remembering and knowing in a patient with preserved recognition and impaired
      recall.
AB  - ROB is a patient who has a severe deficit in recalling recently presented verbal
      material following rupture and repair of an anterior communicating artery
      aneurysm [Hanley JR, Davies ADM, Downes J, Mayes A. Cognitive Neuropsychology
      1994;11:543-78; Hanley JR, Davies ADM. In: Parkin A, editor. Case Studies in the
      Neuropsychology of Memory. Hillsdale, NJ: Lawrence Erlbaum, 1997. p. 111-26].
      Despite this, her performance on tests of recognition memory is comfortably
      within the normal range. In the present series of experiments, we investigated
      whether or not ROB's performance on tests of recognition memory might be
      associated with a disproportionately large number of correct decisions made on
      the basis of familiarity rather than contextual retrieval [e.g. Mandler G.
      Psychological Review 1980;87:252-71]. Contrary to this hypothesis, the results
      showed that ROB made a high proportion of remember decisions relative to know
      decisions in recognition [cf. Gardiner JM. Memory & Cognition 1988;16:309-13] and
      produced a high recollection score when conscious recollection and familiarity
      were placed in opposition to one another [cf. Jacoby LL, Woloshyn V, Kelley C.
      Journal of Experimental Psychology: General 1989;118:115-25.]. ROB's recognition
      memory performance therefore appears to be qualitatively as well as
      quantitatively similar to that found in the normal population. As ROB has
      suffered damage to both the fornix and the anterior thalamus, the results of the
      present study are consistent with the claim that damage to the extended
      hippocampal system has a much more severe effect on recall than on recognition
      [Aggleton JP, Shaw C. Neuropsychologia 1996;34:51-62; Aggleton JP, Saunders RC.
      Memory 1997;5:49-71]. The present results provide no support, however, for the
      additional suggestion [Aggleton JP, Brown MW. Behavioral and Brain Sciences
      1999;22:425-56.] that the extended hippocampal system is necessary for
      recognition memory decisions that are based on contextual retrieval.

PMID- 11516452
TI  - Venous thromboembolism and occult malignancy.
AB  - Trousseau is considered to be the first to have recognised a relation between
      venous thromboembolism (VTE) and malignancy. Illtyd James and Matheson in 1935
      were the first in the Anglo-Saxon literature, at least to our knowledge, to
      report the observation of a patient with occult cancer at time of his venous
      thrombosis. Meanwhile, cancer has become an established risk factor for VTE. The
      prevalence of concomitant cancer in patients presenting with VTE varies
      considerably between the studies due to differences in, for instance, threshold
      of suspicion, screening methods, and characteristics of the patients like age. A
      consistent observation is the low prevalence of concomitant cancer in patients
      with secondary thrombosis, comparable to the prevalence in the general
      population. A 3-19-fold increase in prevalence of concomitant cancer has been
      reported in patients presenting with an idiopathic VTE. The same applies for
      occult cancer in patients with secondary and idiopathic VTE. The prevalence of
      occult cancer in patients with secondary VTE is comparable with the prevalence of
      cancer in the general population, while the prevalence of occult cancer in
      patients with idiopathic VTE is 4-10%. It seems possible to detect a substantial
      number of additional cancer patients, at time of diagnosis of idiopathic VTE, by
      means of extensive screening. However, results of randomised trials, evaluating
      the effect on survival rate, are lacking.

PMID- 11516453
TI  - Treatment of venous thromboembolism in cancer patients.
AB  - The management of deep vein thrombosis (DVT) and pulmonary embolism (PE) in
      patients with cancer can be a clinical dilemma. Comorbid conditions, warfarin
      failure, difficult venous access, and a high bleeding risk are some of the
      factors that often complicate anticoagulant therapy in these patients. In
      addition, the use of central venous access devices is increasing but the optimal
      treatment of catheter-related thrombosis remains controversial. Unfractionated
      heparin (UFH) is the traditional standard for the initial treatment of venous
      thromboembolism (VTE) but low molecular weight heparins (LMWHs) have been shown
      to be equally safe and effective in hemodynamically stable patients. For long
      term treatment or secondary prophylaxis, vitamin K antagonists remain the
      mainstay treatment. However, the inconvenience and narrow therapeutic window of
      oral anticoagulants make extended therapy unattractive and problematic. As a
      result, LMWHs are being evaluated as an alternative for long-term therapy. New
      antithrombotic agents are being tested in clinical trials and may have the
      potential to replace conventional treatment. The role of inferior vena cava
      filters in cancer patients remains ill defined but these devices remain the
      treatment of choice in patients with contraindications for anticoagulant therapy.

PMID- 11516454
TI  - Venous thromboembolism and cancer: prevention of VTE.

PMID- 11516455
TI  - Molecular basis for the relationship between thrombosis and cancer.
AB  - Cancer patients are highly susceptible to thromboembolic complications, which
      some have estimated accounts for a significant percentage of the morbidity and
      mortality of the disease. Not all of the mechanisms for the production of the
      hypercoagulable state characteristic of cancer are entirely understood. Those
      that are known seem to interdigitate the biology of cancer with the major
      regulatory pathways that mediate blood coagulation, platelet-vessel wall
      interaction, fibrinolysis and inflammatory cytokine production. In other words,
      the events responsible for thrombosis in cancer appears to be a result of an over
      exuberant host response in an attempt to delimit tumor growth. In this brief
      review, therefore, we attempt to put into the context of tumor growth,
      angiogenesis and metastasis the current information about the pathogenesis of
      venous thromboembolism (VTE).

PMID- 11516457
TI  - Functional recovery in chronic paraplegic rats after co-grafts of fetal brain and
      adult peripheral nerve tissue.
AB  - BACKGROUND: In recent years, experimental studies have sought some type of
      functional improvement in traumatic paraplegia by transplanting neural tissue
      into the injured spinal cord. The aim of this work is to study the possibility of
      functional recovery in chronic paraplegic rats after co-transplantation of fetal
      cerebral tissue and adult peripheral nerve tissue. METHODS: Seventy adult female
      Wistar rats were subjected to spinal cord injury at the T6-T8 level, causing
      complete paraplegia. Three months later, in 50 rats (grafted group) the injured
      spinal cord tissue received a graft of fetal brain cortex associated with crushed
      adult peripheral nerve. All the animals (grafted and control groups) were
      subjected to daily rehabilitation procedures from the first week after the
      injury, and evaluated weekly for motor and sensory recovery. Statistical analysis
      of different behavioral data between control and grafted animals was performed
      using the Kruskal-Wallis ANOVA and the nonparametric Wilcoxon test. RESULTS:
      Between 8 and 12 months after transplantation, progressive signs of functional
      recovery were observed in the grafted animals, associated with an increase in
      muscle mass in the lower extremities, findings that were significantly different
      from those in nongrafted animals (p < 0.05). At this time, donor cerebral tissue
      is integrated into previously injured spinal cord and results in formation of
      bundles of nerve fibers that emerge from the area of the transplant and surround
      the spinal cord beneath the lesion. CONCLUSIONS: Delayed co-transplantation of
      fetal cerebral tissue and peripheral nerve tissue can be used to achieve
      anatomical remodeling and long-term functional recovery in rats rendered
      paraplegic as result of severe spinal cord injury. These findings support the
      possibility of functional recovery after chronic traumatic paraplegia.

PMID- 11516459
TI  - Lumbar canal stenosis: a cause of late neurological deterioration in patients
      with spina bifida.
AB  - BACKGROUND: Patients diagnosed with spina bifida may show late deterioration.
      This worsening in their clinical symptoms has been attributed to a multiplicity
      of causes such as secondary tethering of the spinal cord, Chiari II anomaly,
      hydromyelia, diastematomyelia, arachnoid cysts, and dermoid tumors. METHODS: We
      searched the clinical records of patients diagnosed with spina bifida who were
      treated at our hospital for a period of 25 years for the purpose of ascertaining
      the number and etiology of cases of late neurological deterioration. RESULTS: Six
      of 144 patients with open spina bifida presented with late neurological
      deterioration. In one of these cases and in another patient with occult spina
      bifida the most relevant factor noted during surgery was the presence of marked
      lumbar canal stenosis. CONCLUSION: We suggest that certain cases of late clinical
      worsening in spina bifida patients are because of lumbar canal stenosis and that
      this condition should be added to the list of causes that may produce delayed
      neurological deterioration in patients with spinal dysraphism.

PMID- 11516461
TI  - A case of primary spinal intramedullary lymphoma.
AB  - A 41-year-old male presented to our clinic with a 1-month history of left
      hemiparesis. He had marked left arm weakness. The diagnostic work-up revealed an
      intramedullary mass at spinal level C2-4. Laminectomies were performed at C2-3-4
      and the tumor was subtotally resected. Histological examination identified the
      mass as a non-Hodgkin's diffuse B-cell lymphoma. The patient was treated with
      corticosteroids, chemotherapy, and adjuvant radiotherapy. The residual tumor
      tissue had completely disappeared by 6 months of follow-up; however, the patient
      presented with intraventricular metastasis at 11 months postsurgery.

PMID- 11516463
TI  - Surgical management of meningioma en plaque of the sphenoid ridge.
AB  - BACKGROUND: Meningioma en plaque represents a morphological subgroup within the
      meningiomas defined by a carpet or sheet-like lesion that infiltrates the dura
      and sometimes invades the bone. Differential diagnosis includes fibrous
      dysplasia, osteoma, and osteoblastic metastasis. This study was conducted to
      obtain pathological information on patients with meningioma en plaque and to
      correlate with the surgical management. METHODS: A retrospective review of all
      the adult operative cases at the University Hospital in a seven and a half-year
      period from July 1, 1990 to December 31, 1997 identified 150 patients who were
      operated on for intracranial meningiomas. The medical records were reviewed to
      identify cases of meningioma en plaque. Forty-seven patients had involvement of
      the sphenoid ridge and 6 of them fulfill the criteria for meningioma en plaque.
      RESULTS: All 6 patients with meningiomas en plaque were female and had
      hyperostosis of the sphenoid bone. In 5 of them, the bone was sent for
      histopathological examination. Four of those had infiltration of the bone by
      meningioma cells. Proptosis was the most common presentation. Half of the
      patients presented with visual disturbances that improved after surgery. All
      patients were operated using a fronto-temporal approach with orbital
      decompression. CONCLUSION: All the involved bone should be removed to prevent
      recurrence. In those cases with involvement of the cavernous sinus and/or the
      orbital apex, a subtotal but extensive removal combined with bony decompression
      of the cranial nerves at the superior orbital fissure and optic canal frequently
      produces good functional and cosmetic results.

PMID- 11516465
TI  - Extended frontal approach with bilateral orbitofrontoethmoidal osteotomies for
      removal of a giant extracranial schwannoma in the nasopharynx, sphenoid sinus,
      and parapharyngeal space.
AB  - BACKGROUND: Although parapharyngeal schwannomas are not uncommon, schwannomas of
      the nasopharynx and paranasal sinuses are rare lesions. In the absence of
      intracranial extension, they are usually removed with transantral, lateral
      rhinotomy or more complex transfacial approaches. CASE DESCRIPTION: We report a
      24-year-old patient with a giant benign schwannoma involving the superior
      parapharyngeal space, pterygopalatine fossa, nasopharynx, and sphenoid sinus with
      erosion into the clivus that was removed with an extended frontal approach
      including bilateral orbitofrontoethmoidal osteotomies. CONCLUSION: The advantages
      of the extended subfrontal over more standard transfacial approaches for lesions
      in this location include the early dissection of critical neural structures,
      preserving cosmetics and facilitating management of an inadvertent cerebrospinal
      fluid leak.

PMID- 11516467
TI  - Calcium channel antagonists inhibit growth of subcutaneous xenograft meningiomas
      in nude mice.
AB  - BACKGROUND: We have previously shown that calcium channel antagonists inhibit in
      vitro meningioma growth. This study examines the effect of calcium channel
      antagonists on in vivo xenograft meningioma growth. METHODS: Meningioma cells
      taken from human patients were mixed with Matrigel and injected into the
      subcutaneous space in the flank of nude mice. These animals were treated with
      calcium channel antagonists in their drinking water. Tumor volumes were measured
      over time; comparison was made between control and treatment groups. Daily
      weights, average daily water consumption, and serum calcium channel antagonist
      levels were determined. Comparison of histology and proliferation index was made
      between control and treatment groups. RESULTS: Diltiazem treatment decreased
      tumor growth over time compared to control groups. Increased tumor growth
      inhibition was seen with increasing doses (p > 0.05). Treatment with verapamil
      had similar effects; however, there are no statistically significant dose
      dependent decreases in growth with increasing verapamil doses. There were no
      tumor "cures" or spontaneous regression of tumor in any group including the
      control groups. Animal daily weight and average daily water consumption was
      unaffected by increasing calcium channel antagonist doses compared to control
      groups. Mouse serum drug levels increased with increasing doses of drug in the
      drinking water of treatment groups (p > 0.05). Histology and proliferative index
      of treatment groups were similar to control groups. CONCLUSION: Calcium channel
      antagonists decrease but do not completely inhibit the growth of meningiomas in
      nude mice. Clinical correlations and potential applications are discussed.

PMID- 11516470
TI  - Visceral cancer metastasis to pituitary adenoma: report of two cases.
AB  - BACKGROUND: We report two cases of metastases from visceral cancers to pituitary
      adenomas, and review the literature. CASE DESCRIPTION: Two female patients, aged
      75 and 87 years, underwent transesophageal surgery for presumably benign
      pituitary adenomas. Using extensive immunostaining studies, histopathological
      examination showed that the surgical specimens from both patients were composed
      of metastatic deposits within gonadotropin adenomas. Fourteen cases of metastases
      to pituitary adenomas have been mentioned in 11 reports in the literature. In all
      cases, the correct diagnosis was made after autopsy or histopathological studies,
      even in patients known to suffer from visceral malignancies. In our cases,
      immunohistochemical studies were conclusive in characterizing the two distinct
      tumor components. The pathogenetic mechanisms favoring the development of
      metastases in pituitary adenomas are discussed, especially those altering the
      normal hypophyseal circulation. CONCLUSION: Neurosurgeons performing pituitary
      surgery should be aware of the possibility of metastases in pituitary adenomas.

PMID- 11516471
TI  - Transluminal stent-assisted coil embolization of a vertebral confluence aneurysm:
      technique report.
AB  - BACKGROUND: Recent advances in stent technology have allowed for negotiation of
      often tortuous posterior circulation intracranial vasculature. Stent-assisted
      coil embolization is a novel treatment for complex wide-necked aneurysms, as
      stents provide a buttress that allows for coil deposition while preventing coil
      herniation into the parent vessel lumen. We describe a case of stent-assisted
      coil embolization of a complex wide-necked vertebral confluence aneurysm. CASE
      DESCRIPTION: A 61-year-old woman presented with a Hunt-Hess III, Fisher Grade III
      subarachnoid hemorrhage secondary to a ruptured vertebral confluence aneurysm
      demonstrated on angiography. The patient underwent emergent angiography and
      attempted coiling of a vertebral confluence aneurysm. Because of the aneurysm's
      complex wide neck and the presence of subclavian steal syndrome, the coils
      repeatedly herniated into the left vertebral and basilar artery lumina. A
      flexible coronary stent was deployed across the aneurysm neck, preventing coil
      herniation and allowing for greater coil deposition. The patient tolerated the
      procedure and underwent repeat coiling 2 months postoperatively because of mild
      coil compaction. This resulted in 100% occlusion and the patient is
      neurologically normal except for a sixth nerve palsy which had been present after
      the hemorrhage. CONCLUSION: Recent advances in stent technology allow negotiation
      of the tortuous posterior circulation vasculature. Stent-assisted coil
      embolization of complex, wide-necked vertebral confluence aneurysms may be an
      alternative intervention for these surgically challenging lesions.

PMID- 11516473
TI  - Prevention of cerebral vasospasm by a capsaicin derivative, glyceryl nonivamide,
      in an experimental model of subarachnoid hemorrhage.
AB  - BACKGROUND: Cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH)
      remains a major complication in patients suffering from SAH. In our previous
      study, we reported that stimulating vascular K(+) channel activity prevented the
      development of cerebral vasospasm. Recent evidence indicates that glyceryl
      nonivamide (GLNVA), a capsaicin derivative, has a vasorelaxant effect on the
      aortic vascular smooth muscle due to the release of coronary calcitonin gene
      related peptide, which in turn stimulates K(+) channel opening. The purpose of
      the present study was to examine the preventive effects of GLNVA on vasospasm.
      METHODS: New Zealand white rabbits were subjected to experimental SAH by
      injecting autologous blood into the cisterna magna. GLNVA or vehicle was injected
      intrathecally immediately after the induction of SAH. All animals were killed by
      perfusion-fixation at 48 hours after SAH. The basilar arteries were removed and
      sectioned, and their cross-sectional areas were measured. RESULTS: The average
      cross-sectional areas of basilar arteries were reduced by 69% and 71% in the SAH
      only and SAH plus vehicle groups, respectively, when compared with the healthy
      controls. After treatment with 0.35, 1.75, and 3.5 mg/kg GLNVA in rabbits
      subjected to SAH the average cross-sectional area was decreased by 46%, 12% and
      2%, respectively, when compared with the healthy controls. The protective effect
      of GLNVA achieved statistical significance at all dosages. Morphologically,
      corrugation of the internal elastic lamina of vessels was often observed in the
      vehicle-treated group, but was not prominent in the GLNVA-treated groups or
      healthy controls. CONCLUSION: The findings showed that GLNVA dose-dependently
      attenuated cerebral vasospasm after SAH in the rabbit. These results suggest that
      intrathecal administration of GLNVA could be an effective strategy for preventing
      cerebral vasospasm after SAH.

PMID- 11516475
TI  - Vertex epidural hematoma associated with traumatic arteriovenous fistula of the
      middle meningeal artery: a case report.
AB  - BACKGROUND: Vertex epidural hematomas are rare. We describe the features of a
      vertex epidural hematoma associated with an arteriovenous fistula (AVF) of the
      meningeal artery created by a laceration of the dura mater underlying a linear
      skull fracture. Although AVF associated with convexity epidural hematomas has
      been reported, we know of no such previous report of vertex epidural hematomas.
      CASE DESCRIPTION: A 65-year-old woman presented with generalized headache
      following head injury. On hospital day 3, she developed a left hemiparesis.
      Magnetic resonance imaging (MRI) disclosed a thick epidural hematoma at the
      vertex. Cerebral angiography showed an AVF between the middle meningeal artery
      and a venous lake. On hospital day 4, the epidural hematoma was evacuated.
      CONCLUSION: Although coronal MRI was important for diagnosis of this vertex
      epidural hematomas, the case particularly illustrates the importance of cerebral
      angiography. The delayed onset of hemiparesis most likely reflected a continuing
      increase in hematoma volume because of bleeding from the lacerated meningeal
      artery.

PMID- 11516476
TI  - Progress and paradox.

PMID- 11516477
TI  - The hyperdynamic circulation in cirrhosis: an overview.
AB  - The hyperdynamic circulation begins in the portal venous bed as a consequence of
      portal hypertension due to the increased resistance to flow from altered hepatic
      vascular morphology of chronic liver disease. Dilatation of the portal vein is
      associated with increased blood flow, as well as the opening up or formation of
      veno-venous shunts and splenomegaly. At the same time, portal hypertension leads
      to subclinical sodium retention resulting in expansion of all body fluid
      compartments, including the systemic and central blood volumes. This blood volume
      expansion is associated with vasorelaxation, as manifested by suppression of the
      renin--angiotensin--aldosterone system, initially only when the patient is in the
      supine position. Acute volume depletion in such patients results in normalisation
      of the hyperdynamic circulation, whilst acute volume expansion results in
      exaggerated natriuresis. As liver disease progresses and liver function
      deteriorates, the systemic hyperdynamic circulation becomes more manifest with
      activation of the renin--angiotensin--aldosterone system. The presence of
      vasodilatation in the presence of highly elevated levels of circulating
      vasoconstrictors may be explained by vascular hyporesponsiveness due to increased
      levels of vasodilators such as nitric oxide, as well as the development of an
      autonomic neuropathy. However, vasodilatation is not generalised, but confined to
      certain vascular beds, such as the splanchnic and pulmonary beds. Even here, the
      status may change with the natural history of the disease, since even portal
      blood flow may decrease and become reversed with advanced disease. The failure of
      these changes to reverse following liver transplantation may be due to
      remodelling and angiogenesis.

PMID- 11516478
TI  - Cirrhosis of the liver and receptor-mediated function in vascular smooth muscle.
AB  - Altered regulation of receptors on the vascular smooth muscle has been proposed
      as one of the mechanisms that may account for the vascular abnormalities in
      patients with cirrhosis of the liver. Impaired contractility and down-regulation
      of contractile receptors have been demonstrated in cirrhotic patients and animal
      models, although interpretation of the literature is hampered by methodological
      variation and conflicting results. There is little evidence, however, that
      receptor down-regulation is the cause of contractile dysfunction in either
      patients or animal models. Receptor desensitisation may contribute to impaired
      contraction in human arteries, but further investigation is required to confirm
      this possibility.

PMID- 11516479
TI  - Vascular smooth muscle cell signaling in cirrhosis and portal hypertension.
AB  - Abnormal vascular responsiveness to ligands has been frequently observed in
      cirrhosis and portal hypertension, but its existence is not proven. The signaling
      pathways in vascular smooth muscle cells (VSMCs) have been studied only in animal
      models of cirrhosis and portal hypertension. Emerging evidence suggests that
      active relaxation, expressed as augmented content or activity of effectors within
      the cyclic AMP signaling pathway and suppressed content or activity of effectors
      in the inositol 1,4,5-trisphosphate/1,2-diacylglycerol signaling pathway, may be
      occurring in VSMCs of the splanchnic circulation in portal hypertension. The
      evidence supporting the existence of this phenomenon in the VSMCs of
      extrasplanchnic circulations in portal hypertension, as well as in the splanchnic
      circulation when chronic cellular damage is present, is very limited. The status
      of the other signaling pathways associated with contractile functions of the
      VSMCs, viz., cyclic GMP and tyrosine kinase-linked pathways, is unknown. The
      status of all the signaling pathways in non-contractile functions of VSMCs, such
      as growth and remodeling, has not been studied. As our overall understanding on
      the signaling pathways in VSMCs is only emerging, it is premature to implicate
      altered activity of the signaling pathways as the underlying basis of vascular
      hyporesponsiveness in cirrhosis and portal hypertension, and to extrapolate these
      limited observations to the human condition.

PMID- 11516480
TI  - Endothelial dysfunction in cirrhosis and portal hypertension.
AB  - Portal hypertension (PHT) is a common clinical syndrome associated with chronic
      liver diseases; it is characterized by a pathological increase in portal
      pressure. Pharmacotherapy for PHT is aimed at reducing both intrahepatic vascular
      tone and elevated splanchnic blood flow. Due to the altered hemodynamic profile
      in PHT, dramatic changes in mechanical forces, both pressure and flow, may play a
      pivotal role in controlling endothelial and vascular smooth muscle cell
      signaling, structure, and function in cirrhotics. Nitric oxide, prostacyclin,
      endothelial-derived contracting factors, and endothelial-derived hyperpolarizing
      factor are powerful vasoactive substances released from the endothelium in
      response to both humoral and mechanical stimuli that can profoundly affect both
      the function and structure of the underlying vascular smooth muscle. This review
      will examine the contributory role of hormonal- and mechanical force-induced
      changes in endothelial function and signaling and the consequence of these
      changes on the structural and functional response of the underlying vascular
      smooth muscle. It will focus on the pivotal role of hormonal and mechanical force
      induced endothelial release of vasoactive substances in dictating the reactivity
      of the underlying vascular smooth muscle, i.e., whether hyporeactive or
      hyperreactive, and will examine the extent to which these substances may exert a
      protective and/or detrimental influence on the structure of the underlying
      vascular smooth muscle in both a normal hemodynamic environment and following
      hemodynamic perturbations typical of PHT and cirrhosis. Finally, it will discuss
      the intracellular processes that regulate the release/expression of these
      vasoactive substances and that control the transformation of this normally
      protective cell to one that may promote the development of vasculopathy in PHT.

PMID- 11516481
TI  - Oxidative stress and vascular smooth muscle cell function in liver disease.
AB  - Reactive oxygen species and reactive nitroxy species are now being recognized as
      regulatory molecules in signaling pathways influencing contractile and
      noncontractile functions of healthy vascular smooth muscle cells. In liver
      disease, oxidative stress is a systemic phenomenon, whose extent correlates with
      the severity of disease. A role for oxidative stress in the development of the
      hyperdynamic circulation in portal hypertension has been proposed. Evaluation of
      the limited available data indicates that it is premature to conclude that
      oxidative stress per se impacts on vascular smooth muscle cell function in liver
      disease.

PMID- 11516483
TI  - Substitution of a commercially available, RNA extraction procedure in an HIV-1
      genotyping system improves sensitivity and allows reduced sample volume.
AB  - The use is described of a commercially available, silica-based extraction
      procedure for HIV-1 RNA that can be substituted for the extraction procedure
      supplied with a commercially available, PCR-based genotyping kit for HIV-1. The
      advantages of using this alternative, commercially available extraction procedure
      include the following: (1) reduced safety concerns, due to inactivation of virus
      in the initial step of the extraction procedure; (2) enhanced sensitivity,
      allowing the use of plasma with HIV-1 RNA levels of less than 2000 copies/ml; (3)
      improved yield, allowing a 60% reduction in plasma volume; and (4) convenience
      and improved reproducibility, with a single extraction providing RNA suitable for
      PCR-based sequencing and for quantitation of HIV-1 RNA levels.

PMID- 11516484
TI  - Investigating hepatitis C virus heterogeneity in a high prevalence setting using
      heteroduplex tracking analysis.
AB  - Hepatitis C virus (HCV) infection is very common among chronic hemodialysis
      patients. In the past, blood transfusion appeared to be the primary risk factor;
      however evidence of nosocomial HCV transmission in the hemodialysis setting has
      recently been reported. This report describes a molecular investigation of HCV
      isolates obtained from a population of 670 patients attending six different
      Seattle-King County based hemodialysis centers in order to identify potential
      common source infections. 733 serum specimens were collected from hemodialysis
      patients in 1992 and 1996, and were tested for HCV antibodies and RNA. Overall,
      115 of 670 (17%) patients were positive for HCV RNA, and thus were considered
      actively infected by HCV. HCV genotype was determined in all cases by restriction
      fragment length polymorphism, and 93 patients were found to be infected by HCV
      genotype 1. HCV envelope genes were amplified from the 93 patients with genotype
      1 infection, and were studied in further detail by heteroduplex tracking analysis
      (HTA) using genotype 1a and 1b specific probes derived from the envelope 1 (E1)
      and envelope 2 (E2) genes. Genetic relatedness between pairs of HCV envelope
      genes was estimated by calculating the degree of gel shift relative to homoduplex
      controls. Nucleotide sequencing and phylogenetic analysis was used to confirm
      genetic relatedness detected by HTA. When HTA was performed using the E1 gene
      probe, 12 apparently related infections were detected; 10 of 12 (83%) of these
      infections were confirmed as truly related using the gold standard method of
      nucleotide sequencing plus phylogenetic analysis. Using an E2 gene probe, 24
      infections were apparently related, but only six (25%) were confirmed by
      sequencing. As a control, 41 envelope genes, which were unrelated by HTA, were
      sequenced; 0 of 41 (0%) were truly related. In summary, HTA provides a rapid and
      effective molecular technique for screening HCV genetic relatedness in population
      based studies, and should prove valuable in future studies of HCV molecular
      epidemiology.

PMID- 11516485
TI  - A chemiluminescence detection method of hantaviral antigens in neutralisation
      assays and inhibitor studies.
AB  - A protocol for chemiluminescence detection of hantaviral antigens in infected
      cell foci is described. This focus detection is based on the conversion of a
      substrate into a luminescent product by peroxidase-antibody conjugates; the
      emitted light of infected cell foci can easily be recorded by autoradiography or
      video imaging providing a hard copy for documentation. The main advantage of this
      method as compared to conventional immunochemical staining is a higher detection
      sensitivity due to the inherent magnification effect of luminescence causing an
      obvious boost in focal image and intensity. This enables reduction of (i)
      incubation time of virus-infected cells and (ii) amount of needed antibody for
      antigen detection in foci. This method is applied to a chemiluminescence focus
      reduction assay for the serotyping of hantavirus-specific neutralising antibodies
      in infected persons and for the determination of activity of antiviral agents
      against hantavirus.

PMID- 11516486
TI  - Detection of herpes viruses in clinical samples using real-time PCR.
AB  - Herpes viruses including cytomegalovirus, varicella zoster and herpes simplex are
      an important cause of morbidity and mortality, especially in immunocompromised
      patients. Real-time PCR assays were developed with the aim of introducing a rapid
      and sensitive test to replace culture, and as a surveillance system for high-risk
      patients. The assays were optimised using cell culture derived material, and the
      sensitivity ascertained using cloned product before applying to extracted and non
      extracted clinical samples. The sensitivity was between 1--100 virus copies with
      increased sensitivity to detect less than 10 copies possible when an initial
      round of amplification was carried out using external primers. Results were
      available within four hours of receipt compared with a median of 4.4 days for
      culture and immunofluorescence. Real-time PCR was found to be a sensitive and
      rapid method of detecting these viruses and will be a valuable tool for the
      surveillance of immunosuppressed patients.

PMID- 11516487
TI  - Single-step multiplex RT-PCR for simultaneous and colourimetric detection of six
      RNA viruses in olive trees.
AB  - A single-step multiplex RT-PCR was developed for the simultaneous and
      colourimetric detection of six RNA viruses (Cucumber mosaic virus, Cherry leaf
      roll virus, strawberry latent ringspot virus, Arabis mosaic virus, Olive latent-1
      virus and Olive latent-2 virus) which infect olive trees. Six compatible primer
      set for one-step RT-PCR amplification in a single closed-tube and 3' digoxigenin
      labelled probes were designed in optimal, specific and conserved regions. The
      method has been assessed with 195 Spanish field olive trees, suggesting that
      approximately 1.5% of the tested material was infected by Cucumber mosaic virus
      and 0.5% by Cherry leaf roll virus. This method saves time and reagent costs
      compared with monospecific RT-PCR which needs several reactions for the same
      number of tests. Using colourimetric detection, it is possible to analyse many
      samples, it increases sensitivity 10-fold, and whilst facilitating the
      interpretation of results, it avoids the use of gels and the toxic ethidium
      bromide. The method could be used routinely for sanitary and certification
      programmes.

PMID- 11516488
TI  - Isolation and genetic characterization of two G3P5A[3] canine rotavirus strains
      in Italy.
AB  - Two strains of canine rotavirus were isolated from pups with clinical signs of
      gastroenteritis. Both strains were identified by polymerase chain reaction (PCR)
      as G3P5A[3], although restriction endonuclease analysis of the PCR amplicons
      revealed a genetic difference between the two isolates in the VP7 gene. The
      isolation in Italy of canine rotaviruses displaying the same VP7 and VP4
      specificities as in the USA and in Japan, suggests that the G3 and P5A[3] types
      are highly conserved among canine rotavirus strains.

PMID- 11516489
TI  - A rapid method for the identification and differentiation of Helicoverpa
      nucleopolyhedroviruses (NPV Baculoviridae) isolated from the environment.
AB  - A diagnostic method is described for the identification and differentiation of
      nucleopolyhedrovirus (NPV) pathogens of Helicoverpa species (Lepidoptera:
      Noctuidae) isolated from the environment. The method is based on the polymerase
      chain reaction (PCR) used in conjunction with restriction fragment length
      polymorphism (RFLP) analysis and comprises three parts. The first part describes
      procedures for obtaining PCR quality viral DNA from individual diseased H.
      armigera cadavers recovered during bioassay analyses of soil and other types of
      environmental sample. These procedures were modified from standard techniques
      used for the routine purification and dissolution of NPV polyhedra and provided
      an overall PCR success rate of 95% (n=60). The second part describes the design
      of several sets of PCR primers for generating DNA amplification products from
      closely and distantly related NPVs. These PCR primers were designed from
      published DNA sequence data and from randomly cloned genomic DNA fragments
      isolated from a reference H. armigera SNPV (HaSNPV) isolate. The final part of
      the method describes how specific PCR products when digested with specific
      restriction endonuclease enzymes, can be used to generate diagnostic DNA profiles
      (haplotypes) that can be used both to identify heterologous NPVs e.g. Autographa
      californica MNPV and related viruses, and to differentiate genotypic variants of
      Helicoverpa SNPV. In the latter case, only two PCR products and four restriction
      digests were required to differentiate a reference set of 10 Helicoverpa SNPV
      isolates known to differ 0.1--3.5% at the nucleotide level. The diagnostic method
      described below marks the second part of a two-phase quantitative-diagnostic
      protocol that is now being applied to a variety of ecological investigations. In
      particular, its application should lead to a significant improvement in our
      understanding of the distribution and population genetics of Helicoverpa SNPVs in
      the Australian environment, as well as providing a sound basis for the design of
      pre- and post-release monitoring systems for genetically enhanced
      bioinsecticides. It is also likely that this method can be adapted readily to the
      study of other insect pathogen associations important economically.

PMID- 11516490
TI  - An improved method for detection and quantification of differential interactions
      between poliovirus internal ribosome entry site RNA and pyrimidine tract binding
      protein from primary cells.
AB  - Attenuated and pathogenic viral variants are often extremely similar viruses with
      drastically different replication potentials. Despite precise knowledge of viral
      residues responsible for poliovirus attenuation/neurovirulence, molecular
      mechanisms mediating these effects remain poorly understood. Data from numerous
      sources suggest that a functional difference in translation initiation is one
      responsible factor. However, direct evidence, as well as a comprehensive model
      are lacking. Several difficulties, including lack of an assay system to quantify
      differential internal ribosome entry site/pyrimidine tract binding protein
      interaction in relevant systems, have precluded progress. A novel assay system
      that overcomes some difficulties is presented below. The assay uses streptavidin
      paramagnetic particles, biotinylated RNA and glutathione-S-transferase/pyrimidine
      tract binding protein fusion to detect nanogram levels of uncloned cellular
      pyrimidine tract binding protein species that interact with internal ribosome
      entry site RNA. Using this assay, it was shown that pyrimidine tract binding
      protein from primary human monocytes binds to internal ribosome entry site RNA
      from virulent poliovirus better than to that from attenuated virus, while
      pyrimidine tract binding protein from HeLa cells does not distinguish between the
      two internal ribosome entry sites. Since primary human monocytes reflect
      neurovirulence-related differential poliovirus replication, these results suggest
      that pyrimidine tract binding protein may contribute to differential poliovirus
      replication in vivo. This assay also has the potential to be applicable broadly
      to other nucleic acid/protein interactions.

PMID- 11516491
TI  - An indicator cell assay for detection of human cytomegalovirus based on enhanced
      green fluorescent protein.
AB  - An indicator cell line (ML-UL54-EGFP) for the detection of human cytomegalovirus
      (HCMV) by a simple and direct method was developed. The stable line was
      constructed by introducing into mink lung cells an expression cassette that
      contains the enhanced green fluorescent protein (EGFP) reporter gene under the
      control of an HCMV-inducible promoter. The promoter was from the upstream region
      of the HCMV UL54 (pol) gene, an early gene promoter that is activated in the
      early phase of HCMV infection. Following infection with HCMV for 48 h, the stable
      line expressed well detectable level of the EGFP as observed under a fluorescence
      microscope. The sensitivity of the indicator cell assay is at least comparable
      with that of a plaque assay as assessed with a panel of HCMV strains. There were
      no detectable fluorescent cells after inoculations with several viruses other
      than HCMV, indicating high specificity. Analysis with flow cytometry revealed
      that the induced fluorescence from the infected cells was proportional to the
      titer of HCMV inoculated, making it possible to quantify HCMV infectious
      particles. In summary, the EGFP-based indicator cell line is of potential use for
      rapid detection and quantification of HCMV in clinical specimens.

PMID- 11516492
TI  - Efficient isolation of mumps virus from a community outbreak using the marmoset
      lymphoblastoid cell line B95a.
AB  - The incidence of mumps infection in the UK was reduced greatly by vaccination as
      a component of MMR vaccine, but cases and outbreaks continue to occur. Although
      in specialised laboratories RT-PCR is available for detection of mumps virus RNA
      in clinical samples, in routine laboratories virus isolation remains a standard
      method for diagnosing mumps virus infection. Furthermore, isolation of mumps
      virus strains circulating currently is important for monitoring the ability of
      vaccine-induced antibody to neutralise any genotypes recognised recently and to
      detect any changes in phenotype. In this study we compared rhesus monkey kidney
      (RMK) cells with the cell line B95a for mumps virus isolation from twenty throat
      swabs collected during a mumps outbreak in a religious community with low MMR
      coverage. Mumps virus was isolated from eight cases (40%), six were positive in
      both cell cultures and two in only one, all positive samples being collected
      within 2 days of onset. Virus growth in B95a cells was detected by the production
      of a syncytial cytopathic effect, and confirmed by an indirect fluorescent
      antibody test using a mumps monoclonal antibody. The B95a cell line was found to
      be equally as sensitive for mumps isolation as RMK cells, which are regarded as
      the 'gold standard', thus providing an alternative to the use of primary animal
      cell culture.

PMID- 11516493
TI  - On the importance and mechanisms of burst release in matrix-controlled drug
      delivery systems.
AB  - Although the significance of burst release in controlled delivery systems has not
      been entirely ignored, no successful theories have been put forth to fully
      describe the phenomenon. Despite the fact that the fast release of drug in a
      burst stage is utilized in certain drug administration strategies, the negative
      effects brought about by burst can be pharmacologically dangerous and
      economically inefficient. Therefore a thorough understanding of the burst effect
      in controlled release systems is undoubtedly necessary. In this article, we
      review experimental observations of burst release in monolithic polymer
      controlled drug delivery systems, theories of the physical mechanisms causing
      burst, some of the unique ideas used to prevent burst, and the treatment of burst
      release in controlled release models.

PMID- 11516494
TI  - Structure and design of polymeric surfactant-based drug delivery systems.
AB  - The review concentrates on the use of polymeric micelles as pharmaceutical
      carriers. Micellization of biologically active substances is a general phenomenon
      that increases the bioavailability of lipophilic drugs and nutrients. Currently
      used low-molecular-weight pharmaceutical surfactants have low toxicity and high
      solubilization power towards poorly soluble pharmaceuticals. However, micelles
      made of such surfactants usually have relatively high critical micelle
      concentration (CMC) and are unstable upon strong dilution (for example, with the
      blood volume upon intravenous administration). On the other hand, amphiphilic
      block co-polymers are also known to form spherical micelles in solution. These
      micelles have very high solubilization capacity and rather low CMC value that
      makes them very stable in vivo. Amphiphilic block co-polymers suitable for
      micelle preparation are described and various types of polymeric micelles are
      considered as well as mechanisms of their formation, factors influencing their
      stability and disintegration, their loading capacity towards various poorly
      soluble pharmaceuticals, and their therapeutic potential. The basic mechanisms
      underlying micelle longevity and steric protection in vivo are considered with a
      special emphasis on long circulating drug delivery systems. Advantages and
      disadvantages of micelles when compared with other drug delivery systems are
      considered. New polymer-lipid amphiphilic compounds such as diacyillipid
      polyethylene glycol, are described and discussed. These compounds are very
      attractive from a practical point of view, since they easily micellize yielding
      extremely stable micelles with very high loading capacity. Micelle passive
      accumulation in the areas with leaky vasculature (tumors, infarct zones) is
      discussed as an important physiology-based mechanism of drug delivery into
      certain target zones. Targeted polymeric micelles prepared by using thermo- or pH
      sensitive components or by attaching specific targeted moieties (such as
      antibodies) to their outer surface are described as well as their preparation and
      some in vivo properties. The fast growing field of diagnostic micelles is
      analyzed. Polymeric micelles are considered loaded with various agents for gamma,
      magnetic resonance, and computed tomography imaging. Their in vitro and in vivo
      properties are discussed and the results of the initial animal experiments are
      presented.

PMID- 11516495
TI  - Recyclable characteristics of hyaluronate-polyhydroxyethyl acrylate blend
      hydrogel for controlled releases.
AB  - Hyaluronate-hydroxyethyl acrylate blend hydrogels which have a wide range of
      composition and characteristics were investigated. Glycidyl methacrylate
      derivatized hyaluronate (GMA-HA) were synthesized by coupling GMA to hyaluronate
      (HA) in the presence of a photoinduced initiator for polymerization. By
      copolymerizing radically GMA-HA and hydroxyethyl acrylate (HEA) under various
      compositions (weight ratios of HEA and GMA-HA: 1-20), GMA-HA hydrogels could be
      prepared in wide ranges of characteristics. These HA-PHEA gels possessed the
      feature that the dried ones recovered completely to the original swelling states
      on repeated runs, i.e. recyclable gels. The water contents of these hydrogels in
      equilibrium swellings in water (W(w)) were 0.99-0.86, and their viscoelastic
      properties were measured by a creep. The spontaneous elastic moduli were
      1.05x10(5)-1.94x10(5) N m(-2), and they were mechanically tough. Their effective
      charge densities were estimated from the partition coefficients of sodium
      benzoate (NaBA) and decreased from -0.033 to -0.044 mol dm(-3) with increasing
      contents of HEA. Release of NaBA was studied, and the diffusion coefficients were
      found to be from 6.95x10(-10) to 0.12x10(-10) m(2) s(-1) with increasing the
      ratio of HEA. Their diffusion coefficients were found to be much less than the
      values estimated from the lattice model.

PMID- 11516496
TI  - Evaluation of derivatives of 3-(2-oxo-1-pyrrolidine)hexahydro-1H-azepine-2-one as
      dermal penetration enhancers: side chain length variation and molecular modeling.
AB  - The present study examined the enhancement effect of two series of compounds
      derived from 3-(2-oxo-1-pyrrolidine)hexahydro-1H-azepine-2-one. One series
      possessed alkyl side chains (series I) and the other alkyl ester side chains
      (series II). An in vitro diffusion study was performed to investigate the effect
      of variation in alkyl/alkyl ester side chain length of two series of compounds on
      the permeation of hydrocortisone (HC) across hairless mouse skin. The
      permeability coefficient (P), 24 h receptor concentration (Q(24)) and skin
      content (SC), as well as the enhancement ratios (ER) for each parameter were
      recorded. A parabolic relationship was observed between the ER(P), and the alkyl
      side chain length of the enhancers. The relationship between the length of ester
      side chains and ER(P) appeared to be relatively linear with R(2) of 0.9676. The
      relationship between the calculated lipophilicity (CL) and enhancement activity
      of the enhancers showed that for CL 5-9, series I showed higher P values compared
      with Azone, but this was not observed with series II. For CL values 4.57-7.75, a
      significant correlation existed between P of HC and CL of series II compounds
      (R(2)=0.9967). 1-Tetradecyl-3-(2-oxo-1-pyrrolidine)-epsilon-caprolactam showed
      the highest P and Q(24), with 40.5- and 18.6-fold increases over the control. In
      conclusion, the alkyl side chain series of compounds showed more enhancing
      activity than the alkyl ester side chain series.

PMID- 11516497
TI  - Electrically-assisted transdermal delivery of buprenorphine.
AB  - The objective of this study was to explore the electrically assisted transdermal
      delivery of buprenorphine. Oral delivery of buprenorphine, a synthetic opiate
      analgesic, is less efficient due to low absorption and large first-pass
      metabolism. While transdermal delivery of buprenorphine is expected to avoid the
      first-pass effect and thereby be more bioavailable, use of electrical enhancement
      techniques (iontophoresis and/or electroporation) could provide better
      programmability. Another use of buprenorphine is for opiate addiction therapy.
      However, a patch type device is subject to potential abuse as it could be removed
      by the addict. This abuse can be prevented if drug particles are embedded in the
      skin. The feasibility of doing so was investigated by electro-incorporation.
      Buprenorphine HCl (1 mg/ml) in citrate buffer (pH 4.0) was delivered in vitro
      across human epidermis via iontophoresis using a current density of 0.5 mA/cm(2)
      and silver-silver chloride electrodes. Electroporation pulses were also applied
      in some experiments. For electro-incorporation, drug microspheres or particles
      were driven into full thickness human skin by electroporation. It was observed
      that the passive transdermal flux of buprenorphine HCl was significantly enhanced
      by iontophoresis under anodic polarity. The effectiveness of electro
      incorporation seemed inconclusive, with pressure also playing a potential role.
      Delivery was observed with electro-incorporation, but the results were
      statistically not different from the corresponding controls.

PMID- 11516498
TI  - Sustained ophthalmic delivery of ofloxacin from a pH triggered in situ gelling
      system.
AB  - The poor bioavailability and therapeutic response exhibited by conventional
      ophthalmic solutions due to rapid precorneal elimination of the drug may be
      overcome by the use of in situ gel-forming systems that are instilled as drops
      into the eye and undergo a sol-gel transition in the cul-de-sac. The present work
      describes the formulation and evaluation of an ophthalmic delivery system of an
      antibacterial agent, ofloxacin, based on the concept of pH-triggered in situ
      gelation. Polyacrylic acid (Carbopol 940) was used as the gelling agent in
      combination with hydroxypropylmethylcellulose (Methocel E50LV) which acted as a
      viscosity enhancing agent. The developed formulation was therapeutically
      efficacious, stable, non-irritant and provided sustained release of the drug over
      an 8-h period. The developed system is thus a viable alternative to conventional
      eye drops.

PMID- 11516499
TI  - Evaluation of in vivo release characteristics of protein-loaded biodegradable
      microspheres in rats and severe combined immunodeficiency disease mice.
AB  - The in vivo release characteristics of protein-loaded biodegradable microspheres
      were examined in normal rats and severe combined immunodeficiency disease (SCID)
      mice. Bovine-derived superoxide dismutase (bSOD), encapsulated into microspheres
      comprised of poly(D,L-lactic-co-glycolic acid) and poly(D,L-lactic acid), was
      used as a model protein. Three types of bSOD-loaded microspheres with different
      release profiles were subcutaneously administered to normal rats. Anti-bSOD
      antibodies were first detected at day 9 after the administration of these
      microspheres, which was independent of their release profiles in vitro. A typical
      formulation with a sigmoidal release profile was subcutaneously administered to
      SCID mice. No immunoreaction was observed. The plasma bSOD concentration-time
      profile, determined by an enzyme-linked immunosorbent assay, well reflected the
      in vitro release profile of the formulation. The disappearance profile of active
      bSOD from the administration site also partly corresponded to both profiles.
      However, the relative bioavailability calculated with a profile on the
      subcutaneous injection of bSOD solution was 40.7%. These results indicated
      possible instability of bSOD released gradually at the administration site. The
      results of the present study using SCID mice would be suitable for discussing the
      in vitro-in vivo correlation of protein release from microspheres, and useful for
      designing long-term release formulations of protein drugs.

PMID- 11516500
TI  - Evaluation of gastric mucoadhesive properties of aminated gelatin microspheres.
AB  - The gastric mucoadhesive properties of aminated gelatin microspheres were
      evaluated both in vitro and in vivo. The interactions of gelatin, aminated
      gelatin and microspheres with two kinds of commercial mucin were estimated in
      aqueous media. At a higher mucin concentration, aminated gelatin demonstrated a
      stronger interaction with mucin than either kind of the gelatin (isoelectric
      point (IEP): 5.0 and 9.0) under the same condition, although these interactions
      varied with varying media. At the same time, a larger amount of mucin was
      adsorbed to aminated gelatin microspheres than to either of the gelatin
      microspheres in the same condition. In the in vitro model of isolated and
      perfused rat stomach, the amount of aminated gelatin microspheres that remained
      in the stomach after perfusion was significantly larger than that of gelatin
      microspheres. However, no significant difference was observed whether the test
      was performed in simulated gastric fluid (SGF) or in phosphate-buffered saline
      (PBS, pH7.4). In the in vivo experiment, about 47% of the aminated gelatin
      microspheres remained in the stomach 2 h after oral administration in a capsule,
      whereas it was 29 and 34% for gelatin (IEP=5.0) and gelatin (IEP=9.0)
      microspheres, respectively. These results indicated that aminated gelatin
      microspheres demonstrated a higher gastric mucoadhesive ability than gelatin
      microspheres. The higher amino group content, improved chain flexibility and
      favorable polymer conformation were suggested to be the main factors that
      contributed to the stronger mucoadhesive properties of aminated gelatin
      microspheres than that of gelatin microspheres.

PMID- 11516501
TI  - Pegylation enhances protein stability during encapsulation in PLGA microspheres.
AB  - During encapsulation of proteins in biodegradable microspheres, a significant
      amount of the protein reportedly undergoes denaturation to form irreversible
      insoluble aggregates. Incomplete in vitro release of proteins from the
      microspheres is a common observation. An attempt was made to overcome this
      problem by pegylation of the protein to be encapsulated. Lysozyme, a model
      protein, was conjugated with methoxy polyethylene glycol (mPEG, MW 5000). The
      conjugate was characterized by SDS-PAGE, SE-HPLC, and MALDI-TOF mass
      spectroscopy. The pegylated lysozyme (Lys-mPEG) consisted of different isomers of
      mono-, di- and tri-pegylated with about 15% as native lysozyme. The specific
      activity of the protein was retained after pegylation (101.3+/-10.4%). The
      microsphere encapsulation process was simulated for pegylated and native
      lysozyme. Pegylated lysozyme exhibited much better stability than native lysozyme
      against exposure to organic solvent (dichloromethane), homogenization, and showed
      reduced adsorption onto the surface of blank PLGA microspheres. Release profiles
      of the two proteins from microspheres were very different. For native lysozyme,
      it was high initial release (about 50%) followed by a nearly no release (about
      10% in 50 days). In contrast, Lys-mPEG conjugate showed a triphasic and near
      complete release over 83 days. This study shows that the pegylation of protein
      can provide substantial protection against the destabilization of protein during
      encapsulation.

PMID- 11516502
TI  - Enhanced skin permeation of a lipophilic drug using supersaturated formulations.
AB  - Supersaturation was used to enhance the permeation of a lipophilic model compound
      (a lavendustin derivative, LAP) through excised pig skin in vitro. The drug was
      dissolved in a series of liquid and semisolid vehicles (in which it had different
      solubilities) and which were prepared using either (i) the method of mixed
      cosolvents, (ii) the method of solvent evaporation, or (iii) the method of
      dissolving the drug with heating. Saturated formulations showed comparable
      permeation rates through the skin, independent of the absolute concentration of
      the drug in the vehicle. Supersaturated solutions at a degree of saturation of
      two resulted in a doubling of the drug permeation rate. These experiments show,
      therefore, that the percutaneous absorption of LAP may be consistently increased
      using supersaturated formulations, independent of the type and composition of the
      vehicles and independent of their method of preparation.

PMID- 11516503
TI  - Chitosan nanoparticles as delivery systems for doxorubicin.
AB  - The aim of this paper was to evaluate the potential of chitosan nanoparticles as
      carriers for the anthracycline drug, doxorubicin (DOX). The challenge was to
      entrap a cationic, hydrophilic molecule into nanoparticles formed by ionic
      gelation of the positively charged polysaccharide chitosan. To achieve this
      objective, we attempted to mask the positive charge of DOX by complexing it with
      the polyanion, dextran sulfate. This modification doubled DOX encapsulation
      efficiency relative to controls and enabled real loadings up to 4.0 wt.% DOX.
      Separately, we investigated the possibility of forming a complex between chitosan
      and DOX prior to the formation of the particles. Despite the low complexation
      efficiency, no dissociation of the complex was observed upon formation of the
      nanoparticles. Fluorimetric analysis of the drug released in vitro showed an
      initial release phase, the intensity of which was dependent on the association
      mode, followed by a very slow release. The evaluation of the activity of DOX
      loaded nanoparticles in cell cultures indicated that those containing dextran
      sulfate were able to maintain cytostatic activity relative to free DOX, while DOX
      complexed to chitosan before nanoparticle formation showed slightly decreased
      activity. Additionally, confocal studies showed that DOX was not released in the
      cell culture medium but entered the cells while remaining associated to the
      nanoparticles. In conclusion, these preliminary studies showed the feasibility of
      chitosan nanoparticles to entrap the basic drug DOX and to deliver it into the
      cells in its active form.

PMID- 11516504
TI  - Potential usefulness of solubility index for prediction of the skin permeation
      rate of 5-ISMN from pressure-sensitive adhesive tape.
AB  - Skin permeation of 5-ISMN from pressure sensitive adhesive (PSA) tape was
      evaluated using thermodynamic activity of the drug in PSA. Three acrylic
      adhesives (Gelva 737, Gelva 1430 and Gelva 1753) were used as PSA. Since the drug
      activity in PSA is difficult to determine, however, a solubility index was
      defined. Several PSA tapes containing different amounts of 5-ISMN were prepared,
      and heat of fusion at the dissolution of 5-ISMN in each PSA was determined by
      DSC. No exothermic peak was found when the drug concentration was less than the
      solubility in PSA, whereas the heat of fusion increased proportionally with
      amount of solid drug in the PSA when the drug concentration was above the
      solubility. The bending point in the profile of heat of fusion versus 5-ISMN
      content in PSA was defined as the solubility index. In vitro skin permeation was
      determined using excised hairless rat skin from 5-ISMN-saturated PSA tapes. The
      obtained skin permeation of the drug decreased with increases in the solubility
      index. These profiles were confirmed by a theoretical approach using the
      differential equation corresponding to Fick's second law of diffusion. These
      results suggested that the solubility index can be utilized for prediction of the
      skin permeability of drugs from PSA tape.

PMID- 11516505
TI  - Development of a new drug delivery system for protein drugs using silicone (II).
AB  - In order to achieve a zero-order release of protein drugs, we have developed a
      new drug delivery system using silicone, which is named the covered-rod-type
      formulation. Preparation of the covered-rod-type formulation was conducted under
      mild conditions without heat treatment or the use of organic solvents. The
      covered-rod-type formulation released human serum albumin (HSA) or interferon
      (IFN) at a constant rate for 30-100 days in vitro without significant initial
      burst. When the IFN covered-rod-type formulation was implanted in nude mice, the
      serum IFN concentration was maintained at a constant level during the period of
      observation, i.e., 28 days. The covered-rod-type formulation enabled precise
      control of the release of the protein drugs and would be expected to increase the
      duration of the drug effect and to reduce the frequency of administration and
      side effects.

PMID- 11516506
TI  - Precision and reproducibility of temperature response of a thermo-responsive
      membrane embedded by binary liquid crystals for drug delivery.
AB  - A thermo-responsive membrane embedding with the binary mixture of 36% cholesteryl
      oleyl carbonate (COC) and 64% cholesteryl nonanoate (CN) was successfully
      developed to achieve a rate-controlled and time-controlled drug release in
      response to the skin temperature (i.e., 32 degrees C) of the human body. The
      thermophysical properties of this binary mixture were determined by differential
      scanning calorimetry (DSC) and a microscopic Fourier transform infrared (FT-IR)
      spectrometer equipped with a thermal analyzer (FT-IR/DSC microscopic system). The
      phase transition temperatures of this binary mixture at 35.1 and 64.0 degrees C
      were clearly evidenced by both analytical methods. The temperature response of
      this binary mixture of COC and CN with 36%:64% ratio were also investigated for
      eight cycles by the isothermal FT-IR/DSC microscopic system to continuously and
      repeatedly alter the temperature cycle between 25 and 37 degrees C. The results
      show that this binary mixture revealed a good temperature response in precision,
      sensitivity, obedience and reproducibility. The temperature-sensitive on-off
      pulsatile function of drug penetration through this thermo-responsive membrane
      was investigated. The switching mechanism of this thermo-responsive membrane was
      also proposed. The present result strongly indicates that the binary COC-CN
      mixture-embedded membrane can be used to deliver the drug in a pulsatile fashion
      with respect to skin temperature.

PMID- 11516507
TI  - Poly(lactic acid) microspheres for the sustained release of a selective A1
      receptor agonist.
AB  - A study concerning the feasibility of microsphere use as sustained delivery
      systems for N(6)-cyclopentyladenosine (CPA) administration has been performed.
      The release of this drug and the related stability effects in human whole blood
      have been tested. Moreover, the impact of the delivery system on CPA interaction
      toward human adenosine A1 receptor and the related cellular responses has been
      analyzed. The microspheres were prepared by an emulsion-solvent evaporation
      method using poly(lactic acid). Free and encapsulated CPA was incubated in fresh
      blood and the drug stability was analyzed with HPLC. The affinity of CPA to human
      A1 receptor expressed by CHO cells was obtained by binding experiments. Activity
      was evaluated by measurements of the inhibition of forskolin-stimulated 3',5'
      cyclic adenosine monophosphate (c-AMP) performing competitive binding assays.
      Encapsulated CPA was released within 72 h and its degradation in blood was
      negligible. Affinity and activity values of CPA obtained in the absence and in
      the presence of unloaded microspheres were the same. CPA encapsulation in
      microspheres allows its sustained release and its stabilization in human whole
      blood to be obtained. The presence of this release system does not interfere with
      the CPA activity at its action site.

PMID- 11516508
TI  - Thermoreversible gelation of biodegradable poly(epsilon-caprolactone) and
      poly(ethylene glycol) multiblock copolymers in aqueous solutions.
AB  - The multiblock copolymers composed of poly(ethylene glycol)s (PEGs) and
      biodegradable poly(epsilon-caprolactone)s (PCLs) were synthesized through one
      step condensation copolymerization with hexamethylene diisocyanate (HDI) as a
      coupling agent. The typical phase diagram of these multiblock copolymers in
      aqueous solution displayed a critical gel concentration (CGC) and an upper phase
      transition temperature, which were mainly determined by the PEG/PCL block ratio,
      the PEG or PCL block lengths and the molecular weight. With decreasing PEG/PCL
      block ratio, the CGC decreased with an elevated sol-gel transition temperature on
      account of the enhanced hydrophobicity. The HDI/Diols ratio was used to control
      the molecular weight. At high molecular weights, the CGC decreased, related to
      the enhanced aggregation of PCL blocks and physical crosslinkage between PCL
      block domains due to the increased number of PCL blocks in each molecule. For the
      sample containing the long PCL(2000) block (M(n), 2000), the CGC dropped
      dramatically due to the high hydrophobicity and the poor compatibility between
      PCL and PEG. The dynamic phase transition process was observed by combining
      optical microscopy (OM) and differential scanning calorimetry (DSC) in a certain
      heating/cooling rate. Finally, a possible phase separation-induced gelation
      mechanism is suggested.

PMID- 11516509
TI  - Application of multiple response optimization technique to extended release
      formulations design.
AB  - The purpose of the present study was to apply response surface methodology and
      multiple response optimization utilizing superimposed contour diagrams to design
      extended release formulations with a preplanned release profile. Bumetanide
      solution was layered on sugar pellets followed by coating with various coating
      formulations according to a central composite statistical design using a Glatt
      GPCG 1 Wurster Fluid Bed. The coated pellets were tested for their release
      profiles and the percent of drug released after 1, 4 and 8 h were used to
      describe and optimize the release process. Statistical models describing the
      percent bumetanide released after 1, 4 and 8 h were developed and the
      corresponding contour diagrams were superimposed to predict the coating
      formulation parameters expected to produce target release profile. The pellets
      coated with the designed coating formulation were tested for their release
      profiles in comparison to the target profile. According to the model-independent
      approach using similarity factor (F2), the dissolution profile of the designed
      formulation and the expected target profile were found to be similar. It was
      concluded that response surface methodology and multiple response optimization
      could be successfully used to design and optimize extended release formulations
      with desired preplanned release profile.

PMID- 11516510
TI  - Lipid microparticles as a parenteral controlled release device for peptides.
AB  - To investigate the potential of physiological lipids as an alternative to
      synthetic polymeric materials such as poly(lactide-co-glycolide), peptide
      containing glyceryl tripalmitate microparticles were prepared. A modified solvent
      evaporation method and a melt dispersion technique without the use of organic
      solvent were employed. Thymocartin (TP-4), an immunomodulating tetrapeptide and
      insulin were chosen as model peptides and incorporated as a solid or dissolved in
      100 microl aqueous solution. The resulting microparticles were characterized with
      respect to particle size and morphology, biocompatibility, drug content
      (encapsulation efficiency) and in vitro release behavior. Electron spectroscopy
      for chemical analysis was used to investigate the adsorption of the model
      peptides to the lipid matrix material. The modified solvent evaporation as well
      as the melt dispersion method were suitable for the preparation of microparticles
      in the size range of 20-150 microm with an acceptable yield. The biocompatibility
      of the glyceryl tripalmitate microparticles after implantation into NMRI-mice was
      comparable to poly(lactide-co-glycolide) microparticles. The encapsulation
      efficiency for both model peptides was high (>80%) even at high theoretical
      loadings when the peptide was incorporated as a solution with the melt dispersion
      technique. The in vitro release behavior was substantially influenced by the
      physicochemical properties of the model peptides used in this study.

PMID- 11516511
TI  - Characterization of the influence of polyol fatty acid esters on the permeation
      of diclofenac through rat skin.
AB  - In this study, we investigated the effect of sefsols on the skin to clarify the
      mechanism of the sefsol enhancement effect. In vitro percutaneous absorption
      experiments were performed using Franz diffusion cells. Removal of the stratum
      corneum and delipidization of the skin increased the permeation of diclofenac
      from aqueous suspension, with the enhancement effects being similar for both
      treatments. Further enhancement effects of diclofenac permeation by sefsol
      through the stripped and delipidized skin were not observed. Attenuated total
      reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) was employed to
      investigate the biophysical changes in the stratum corneum lipids by sefsols. One
      of the sefsols, propylene glycol mono caprylate (S-218), induced higher and
      broader absorbance shifts in both asymmetric and symmetric C-H bond stretching
      regions. However, no significant differences were observed among the sefsols with
      respect to peak heights and areas for both absorbances when compared with H2O
      treatment. These results suggest that sefsol may change the lipid-chain fluidity
      of the stratum corneum without lipid extraction. The accumulated amounts of
      diclofenac in the skin significantly increased in the presence of sefsol. Also,
      the amounts of diclofenac in the skin increased with the amount of sefsol in the
      skin. This sefsol enhancement effect was reversed at 12 h after treatment. Thus,
      enhancement of the diclofenac flux by sefsols is reversible and may be due to a
      change in the lipid-chain fluidity of the stratum corneum and improvement in drug
      partitioning to the stratum corneum.

PMID- 11516512
TI  - Copolymers of amine methacrylate with poly(ethylene glycol) as vectors for gene
      therapy.
AB  - A series of structurally related copolymers of tertiary amine methacrylate with
      poly(ethylene glycol) (PEG) were investigated for their potential to serve as
      vectors for gene therapy. The effects of copolymer structure on the complexation
      and transfection ability were assessed. The ability of the PEG-based copolymers
      and DMAEMA homopolymer to bind and condense DNA was confirmed by gel
      electrophoresis, ethidium bromide displacement and transmission electron
      microscopy. The presence of PEG in the copolymers had a beneficial effect on
      their ability to bind to DNA. Colloidally stable complexes were obtained for all
      the PEG-copolymer systems as shown by uniformly discrete spherical images from
      transmission electron microscopy and approximate diameters of 80-100 nm by
      dynamic light scattering studies. DMAEMA homopolymer, however, produced
      agglomerated particles, confirming the important role played by the PEG chains in
      producing compact stable DNA complexes. Assessment of the effect of ionic
      strength of the buffer on the complexation and dissociation of the complexes
      indicated the importance of both electrostatic and non-electrostatic interactions
      in the polymer-DNA complexation. In vitro transfection experiments showed that
      DMAEMA homopolymer gave the highest level of transfection comparable to a control
      poly-L-lysine (PLL) system. The PEG-based copolymers gave reduced levels of
      transfection, most likely due to the steric stabilization effect of a PEG corona.

PMID- 11516513
TI  - Characterization of complexes of an antisense oligonucleotide with protamine and
      poly-L-lysine salts.
AB  - The objectives of this work were to study the interaction of an antisense
      oligonucleotide (ISIS 2302) with poly-L-lysine (PLL) and protamine salts, to
      determine the physico-chemical characteristics of the resulting complex systems
      and to analyze the influence of permeation enhancers (Na-chenodeoxycholate and Na
      caprate) on the dissociation of the complexes. Specific conductivity, zeta
      potential, particle size distribution and dialysis studies of the resulting
      complex systems were performed. Conductometric titration defined the molar ratios
      between the ionic species in the complex. Zeta potential data confirmed the
      conductometric equivalence points and explained the good physical stability of
      charged complexes when compared to neutral complexes (+/-40 mV for PLL-based
      complexes and +/-25 mV for protamine sulfate complexes). The particle size was
      less than 175 nm for most systems. The incorporation of Na-chenodeoxycholate
      promoted complex dissociation, while Na-caprate gave opposite results. An
      increase in the ionic strength of the environment had a destabilizing effect and
      promoted dissociation of the complexes.

PMID- 11516514
TI  - DNA transfection using linear poly(ethylenimine) prepared by controlled acid
      hydrolysis of poly(2-ethyl-2-oxazoline).
AB  - A series of linear poly(ethylenimine) (L-PEI) containing varying amounts of
      cationic charge density in its backbone was produced by controlled hydrolysis of
      poly(2-ethyl-2-oxazoline) (PEtOz) for using as a nonviral DNA transfection agent.
      The effects of cationic charge density and molecular weight of the L-PEI on the
      cytotoxicity and transfection efficiency were studied. The efficiency of
      transfection was monitored by using a luciferase reporter gene system. Gel
      retardation assay and dynamic light scattering (DLS) showed that the condensation
      capacity of L-PEI was suitable for transfection. Highly compacted L-PEI/DNA
      complex ( approximately 150 nm) was obtained with a surface charge value of
      around +28.4 mV. Cell cytotoxicity was affected to a great extent by the
      hydrolysis percent of L-PEI as well as by the molecular weight. Transfection
      efficiency of luciferase plasmid DNA against NIH 3T3 fibroblast was largely
      dependent upon the hydrolysis percent (charge density) in the polymer backbone
      and the molecular weight of the L-PEI, but independent of the total amount of
      cationic charges used for DNA condensation. L-PEI with a hydrolysis percent of
      88.0% exhibited comparable transfection efficiency to that of commonly used
      branched PEI.

PMID- 11516515
TI  - Evaluation of polyplexes as gene transfer agents.
AB  - Non-viral transfection systems based on the complexes of DNA and polycations
      ('polyplexes') were evaluated with respect to their effectiveness, toxicity and
      cell type dependence in a variety of in vitro models. The panel of polycations
      examined included branched and linear polyethyleneimines, poly[N-ethyl-4-vinyl
      pyridinium bromide], polyamidoamine dendrimer (Superfect), poly(propyleneimine)
      dendrimer (Astramol) and a conjugate of Pluronic P123 and polyethyleneimine (P123
      g-PEI(2K)), having a graft-block copolymer architecture. Using a panel of cell
      lines the linear polyethyleneimine ExGen 500, Superfect, branched
      polyethyleneimine 25 kDa, and P123-g-PEI(2K) were determined as systems
      displaying highest transfection activity while exhibiting relatively low
      cytotoxicity. These systems had activity higher than or comparable to lipid
      transfection reagents (Lipofectin, LipofectAMINE, CeLLFECTIN and DMRIE-C) but did
      not reveal serum dependence and were less toxic than the lipids. Overall, this
      study demonstrates good potential of structurally diverse polyplex systems as
      transfection reagents with relatively low cytotoxicity.

PMID- 11516516
TI  - In vitro nephrotoxicity induced by N-(3,5-dichlorophenyl)succinimide (NDPS)
      metabolites in isolated renal cortical cells from male and female Fischer 344
      rats: evidence for a nephrotoxic sulfate conjugate metabolite.
AB  - The agricultural fungicide N-(3,5-dichlorophenyl)succinimide (NDPS) induces
      nephrotoxicity in vivo that is characterized as acute polyuric renal failure and
      proximal tubular necrosis. However, earlier in vitro studies have failed to
      reproduce the in vivo nephrotoxicity seen with NDPS or its nephrotoxic
      metabolites N-(3,5-dichlorophenyl)-2-hydroxysuccinimide (NDHS) and N-(3,5
      dichlorophenyl)-2-hydroxysuccinamic acid (2-NDHSA). The purpose of this study was
      to examine the nephrotoxic potential of NDPS, its known non-conjugated
      metabolites, the O-sulfate conjugate of NDHS (NSC), and the putative metabolite N
      (3,5-dichlorophenyl)maleimide (NDPM) and its hydrolysis product N-(3,5
      dichlorophenyl)maleamic acid (NDPMA) using freshly isolated renal cortical cells
      (IRCC). IRCC were obtained from untreated male or female Fischer 344 rats
      following collagenase perfusion of the kidneys. Cells (approximately 4 million
      per ml) (N=4) were incubated with up to 1.0 mM NDPS or an NDPS metabolite or
      vehicle for up to 120 min. Cytotoxicity was determined by measuring lactate
      dehydrogenase (LDH) release into the medium. Only NSC (>0.5 mM) and NDPM (> or
      =0.5 mM) exposure increased LDH release from IRCC. NSC 1.0 mM or NDPM 0.5 mM
      increased LDH release from IRCC within 15--30 min of exposure. NDPS or the
      remaining NDPS metabolites did not increase LDH release at bath concentrations of
      1.0 mM for exposures of 120 min. IRCC from male and female rats responded
      similarly to the toxic effects of NDPS and its metabolites. These results
      demonstrate that sulfate conjugates of NDPS metabolites can be fast acting
      nephrotoxicants and could contribute to NDPS nephrotoxicity in vivo. These
      results also suggest that the kidney probably accumulates toxic sulfate
      conjugates of NDPS metabolites rather than forming the conjugates. In addition,
      mechanisms responsible for gender differences in nephrotoxicity seen with NDPS
      and NDPS metabolites in vivo either occur prior to renal accumulation of sulfate
      conjugates and/or represent biochemical/physiological differences between the
      genders.

PMID- 11516517
TI  - Prophylactic efficacy of amifostine and its analogues against sulphur mustard
      toxicity.
AB  - The successful implication of the chemical weapons convention stimulated research
      with a new vigour on the destruction of the stockpiled sulphur mustard (SM). A
      prophylactic agent for SM will be very useful for personnel engaged in the
      destruction of SM and during inspections by the Organisation for the Prohibition
      of Chemical Weapons. Due to simple method of preparation, SM can be used
      clandestinely during war or by terrorist groups. Inspite of research over several
      decades no satisfactory prophylactic or treatment regimen has evolved for SM.
      Amifostine an organophosphorothioate, originally developed as a radioprotector,
      and its analogues were evaluated as a prophylactic agent for SM. Three analogues
      by varying the chain length and substitution at the sulphur atom were synthesised
      and coded as DRDE-06, DRDE-07 and DRDE-08. LD(50) of amifostine and its analogues
      were estimated through intraperitoneal (i.p.) route. For the protection studies,
      amifostine and its analogues were administered i.p. in mice, 30 min before dermal
      (percutaneous) application of SM. The dose of the prophylactic agent was 0.2
      LD(50) (i.p.) and that of SM was 152 mg/kg (undiluted) equal to 19-fold LD(50) of
      SM. Amifostine and one of its analogues, DRDE-07 gave significant protection.
      Further studies were carried out using amifostine and DRDE-07, and both of them
      significantly protected mice against SM (155 mg/kg, in PEG 300, equal to 19
      LD(50)) when they were administered i.p. either 30 min before or simultaneously.
      LD(50) of amifostine and DRDE-07 were also estimated through the oral route (1049
      or 1248 mg/kg, respectively). Prophylactically administered amifostine and DRDE
      07 (0.2 LD(50), p.o.) significantly protected the mice against dermally applied
      SM (155 mg/kg, in PEG 300, equal to 19 LD(50)). The protection offered by DRDE-07
      was better than that of amifostine by the oral route. DRDE-07 (0.2 LD(50), p.o.)
      also protected significantly with respect to the decrease in body weight and the
      depletion of GSH induced by SM. DNA damage induced by SM was also significantly
      reduced by amifostine and DRDE-07 (0.2 LD(50), p.o.). Further studies are in
      progress on the various pharmacological and toxicological properties of DRDE-07.

PMID- 11516519
TI  - Comparative uptake behavior of trace elements in adult and suckling rat lens.
AB  - The multitracer technique was applied to the determination of the uptake of trace
      elements in the lenses of adult and suckling rats to investigate the transport
      mechanisms of trace elements during developmental maturation. Be, Sc, V, Mn, Fe,
      Co, Zn, As, Se, Rb, Sr, Y, Zr, Ru and Rh accumulate in adult and suckling rat
      lenses. The rates of uptake of trace elements differ among each species and also
      differ between adult and suckling rat lenses. The uptakes of Fe and Sr are
      greater in adult rat lenses, while the uptakes of Se and Rb are greater in
      suckling rat lenses. High concentrations of Zn are transported into the lenses of
      both adult and suckling rats in comparison with other elements, and the content
      of Zn in suckling rat lens is higher than in adult lens. The present study
      suggests that different mechanisms depending on the stage of development act to
      transport trace elements into lenses.

PMID- 11516518
TI  - Protective effect of metallothionein against the toxicity of cadmium and other
      metals(1).
AB  - Metallothionein (MT) is a small-molecular weight, cysteine-rich protein that
      binds metals. The protective role of MT in Cd toxicity is well established but
      its ability to protect against toxicity of other metals remains unclear. In this
      study, wild-type and MT-I and -II null mice (MT-null mice) were used to determine
      whether MT is protective against the lethality of not only Cd but also Zn, Cu,
      Fe, Pb, Hg and As. Following daily subcutaneous administration of an increasing
      dose of each metal, starting with a low, non-toxic dose, we compared the
      cumulative median lethal dose (LD(50)) of each metal between wild-type and MT
      null mice. The LD(50) of Cd for wild-type mice was 6.9-fold higher than for MT
      null mice. The LD(50) of Zn was 2.4-fold higher for wild-type mice than for MT
      null mice, and 1.4-fold higher for Cu and As. The LD(50) of Hg was 1.3-fold
      higher for wild-type mice than for MT-null mice, but this was not statistically
      significant. No difference in LD(50) values was observed between wild-type and MT
      null mice following Pb and Fe administration. These results suggest that MT is an
      important protein in the cellular defense against Cd toxicity and lethality, but
      it provides much less protection against the lethality of the other metals.

PMID- 11516520
TI  - Lead causes human fibroblasts to mis-sort arylsulfatase A.
AB  - Lead exposure causes cognitive and behavioral deficits in some children. We have
      proposed that the effects of single nucleotide polymorphisms (SNP) of the human
      pseudodeficient arylsulfatase A (ARSA) gene that result in reduced levels of the
      enzyme, and lead concentrations that decrease ARSA activity, culminate in
      cellular enzymic activity that is below a critical threshold required for the
      normal nervous system function. Human fibroblasts grown in the presence of lead
      acetate exhibit a 65% decrease in ARSA protein, resulting in a significant
      decrease in the ability to catabolize sulfatide in cells from individuals with
      the SNP(s) of pseudodeficient ARSA, but not those from subjects with the normal
      gene (Poretz et al., Neurotoxicology 21 (2000) 379). The present study examines
      the potential of lead to affect the biosynthesis, trafficking and turnover of
      ARSA in human fibroblasts. Fibroblasts, grown in 20 microM lead, displayed a 44-
      58% increase in the rate of proliferation. Lead caused a decrease of
      approximately 33% in the accumulation of newly synthesized intracellular ARSA.
      This difference was not due to increased rates of intracellular degradation of
      ARSA or decreased levels of ARSA mRNA. Lead, however, caused the newly
      synthesized enzyme to be trafficked through the secretion pathway, resulting in
      decreased amounts of the enzyme in intracellular compartments. Though lead
      exposure results in increased cellular proliferation, it appears to cause
      decreased intracellular steady-state levels of ARSA by affecting the sorting cues
      and/or mechanisms directing the enzyme to lysosomes.

PMID- 11516521
TI  - Release of mercury from dental amalgam fillings in pregnant rats and distribution
      of mercury in maternal and fetal tissues.
AB  - Mercury vapor released from a single amalgam restoration in pregnant rats and
      mercury concentrations in maternal and fetal rat tissues were studied. Dental
      treatment was given on day 2 of pregnancy. Mercury concentration in air sample
      drawn from the metabolism chamber with the rat was measured serially for 24 h on
      days 2, 8 and 15 of pregnancy. An average mercury concentration in the air
      samples from the rats given amalgam restorations was 678.6+/-167.5 ng/day on day
      2. The average mercury concentration in the air samples tended to decline as time
      elapsed but a marked amount (423.2+/-121.5 ng/day) was observed even on day 15.
      The amount of mercury in the air samples increased 7--20-fold after chewing. The
      placement of the single amalgam restoration (3.8--5.5 mg in weight) increased the
      levels of mercury approximately three to 6 times in the maternal brain, liver,
      lung, placenta and 20 times in the kidneys. The highest mercury concentration
      among fetal organs was found in the liver, followed by the kidneys and brain.
      Mercury concentrations in maternal organs and fetal liver were significantly
      higher than those of the controls, and concentrations in maternal whole blood,
      erythrocytes and plasma, and in fetal whole blood were also significantly higher.
      Mercury concentrations in the fetal brain, liver, kidneys and whole blood were
      lower than those of the maternal tissues.

PMID- 11516522
TI  - Sulfur-to-nitrogen transnitrosation: transfer of nitric oxide from S-nitroso
      compounds to diethanolamine and the role of intermediate sulfur-to-sulfur
      transnitrosation.
AB  - S-Nitrosothiols are formed in vivo and are involved in NO signaling. We
      investigated the sulfur-to-nitrogen transnitrosation activity of S
      nitrosocysteine, S-nitrosoglutathione, S-nitrosohomocysteine, S
      nitrosocysteinylglycine and S-nitroso-N-acetylcysteine in their reaction with the
      secondary amine diethanolamine in vitro. The resulting N-nitrosodiethanolamine, a
      strong carcinogen, was formed in yields of up to 11% from S-nitrosocysteine and S
      nitrosocysteinylglycine, whereas the transnitrosation activity of the other S
      nitroso compounds was weak. However, the addition of L-cysteine to a solution of
      S-nitrosohomocysteine and diethanolamine accelerated the decomposition of S
      nitrosohomocysteine and resulted in a significant formation of N
      nitrosodiethanolamine accompanied by the intermediate generation of S
      nitrosocysteine. Thus, reactive nitrosothiols can be formed from less reactive
      analogs via sulfur-to-sulfur transnitrosation. We suggest that this affects
      regulation of NO trafficking in vivo. The reaction provides an alternative
      mechanism for the generation of carcinogenic N-nitroso derivatives.

PMID- 11516523
TI  - Effects of Lewisite on cell membrane integrity and energy metabolism in human
      keratinocytes and SCL II cells.
AB  - Lewisite is a highly toxic arsenic compound which can cause skin damage. In the
      present study effects of Lewisite on cell membrane integrity and energy
      metabolism as well as antidotal effects of DL-2,3-dimercaptopropanesulfonate
      (DMPS), and meso-2,3-dimercaptosuccinic acid (m-DMSA) were investigated in a
      keratinocyte derived cell line (SCL II) and primary human keratinocytes (HK).
      Cells were incubated in Lewisite (60 microM) containing medium for 5 min. During
      the following 6 h lactate dehydrogenase (LDH) activity in the supernatant,
      intracellular ATP content, tetrazolium reduction, glucose consumption and lactate
      formation were measured. Glucose consumption and lactate production were
      decreased in both cell lines after Lewisite exposure. In SCL II cells an increase
      of LDH activity in the supernatant, a decrease of ATP content, and an impaired
      ability to reduce tetrazolium was found 3 h after Lewisite exposure. In HK
      cultures tetrazolium reduction was significantly decreased already after 2 h,
      whereas LDH increase in the supernatant and ATP content decrease occurred only at
      6 h after Lewisite exposure. When DMPS or m-DMSA was added directly after
      Lewisite exposure to SCL II cells, glucose consumption and lactate formation were
      restored and LDH leakage was prevented. SCL II cells might be more prone to
      membrane damage whereas in keratinocytes mitochondrial impairment seems to be the
      predominant effect of Lewisite.

PMID- 11516524
TI  - Diesel exhaust-induced airway hyperresponsiveness in c-Ha-ras transgenic mice.
AB  - Recently the quantity of diesel exhaust (DE) emissions, which contain a variety
      of chemicals and can induce pulmonary carcinoma in animals, has been increasing
      in Japan. To assess the toxicity of DE, we evaluated airway hyperresponsiveness
      after exposure to DE in the rasH2 (CB6F1-TgHras2) mouse, which carries c-Ha-ras
      genes and shows marked sensitivity to treatment with various genotoxic
      carcinogens such as methylnitrosourea and dimethylbenzanthracene. We exposed
      rasH2 mice (n=18) and their nontransgenic littermates (n=19) to room air or 3
      mg/m(3) DE for 4 weeks, measured their respiratory resistance (Rrs) during
      inhalation of acetylcholine (ACh; 0.005, 0.01, 0.02, 0.04, 0.08, 0.16, 0.31,
      0.63, 1.28, 2.5, 5, or 10 mg/ml) for 2 min, and calculated the provocative ACh
      concentration needed to cause a 50% increase (PC(150)) in Rrs. At all doses of
      ACh, Rrs was significantly higher (P<0.05) in rasH2 mice exposed to DE than in
      those exposed to room air. In addition, Rrs in the DE-exposed rasH2 animals was
      significantly higher (P<0.05) at 0.16, 0.31, and 0.63 mg/ml ACh than in DE
      exposed nontransgenic littermates. The PC(150) (mean+/-standard error) of DE
      exposed rasH2 mice was 3.4+/-1.9 mg/ml, that in rasH2 mice exposed to room air
      was 10.6+/-2.5 mg/ml, and that in DE-exposed nontransgenic animals was 10.9+/-3.7
      mg/ml. In conclusion, DE causes airway hyperresponsiveness in rasH2 mice and may
      induce the expression of c-Ha-ras genes.

PMID- 11516525
TI  - Thiram-induced cytotoxicity is accompanied by a rapid and drastic oxidation of
      reduced glutathione with consecutive lipid peroxidation and cell death.
AB  - The toxic effect of thiram, a widely used dithiocarbamate fungicide, was
      investigated in cultured human skin fibroblasts. Cell survival assays
      demonstrated that thiram induced a dose-dependent decrease in the viable cell
      recovery. Thiram exposure resulted in a rapid depletion of intracellular reduced
      glutathione (GSH) content with a concomitant increase in oxidized glutathione
      (GSSG) concentration. Alteration of glutathione levels was accompanied by a dose
      dependent decrease in the activity of glutathione reductase (GR), a key enzyme
      for the regeneration of GSH from GSSG. Thiram-exposed cells exhibited increased
      lipid peroxidation reflected by enhanced thiobarbituric acid reactive substances
      (TBARS) production, suggesting that GSH depletion and the lower GR activity gave
      rise to increased oxidative processes. To investigate the role of decreased GSH
      content in the toxicity of thiram, GSH levels were modulated prior to exposure.
      Pretreatment of fibroblasts with N-acetyl-L-cysteine (NAC), a GSH biosynthesis
      precursor, prevented both lipid peroxidation and cell death induced by thiram
      exposure. In contrast, thiram cytotoxicity was exacerbated by the previous
      depletion of cellular GSH by L-buthionine-(S,R)-sulfoximine (BSO). Taken
      together, these results strongly suggest that thiram induces GSH depletion,
      leading to oxidative stress and finally cell death.

PMID- 11516526
TI  - Evaluation of teniposide (VM-26)-induced toxicity on mouse spermatogenesis by
      flow cytometry.
AB  - Alteration in the testicular weight and various germ cell populations was studied
      in male mice treated with different doses (0.05, 0.25, 0.5, 1.0 and 2.0 mg/kg b.
      wt.) of teniposide (VM-26) at various post-treatment time periods. Treatment of
      mice with different doses of teniposide did not significantly alter the
      testicular weights, irrespective of the drug dose used. Flow-cytometric analysis
      of germ cells of the untreated control mice testes revealed four distinct DNA
      peaks corresponding to elongated spermatids (HC), round spermatids (1C),
      spermatogonia and non-germ cells (2C) and primary spermatocytes (4C). The region
      between 2C and 4C peaks represents cells that are actively synthesizing DNA (S
      phase cells). Treatment of mice with different doses of teniposide resulted in a
      significant depletion in the relative percentage of spermatogonia from day 2 to
      35 post-treatment depending on the drug dose. DNA-synthesizing, i.e. S-phase,
      cells declined significantly at day 1 post-treatment and continued to decline up
      to day 70 post-treatment for all the drug doses studied, except 2 mg/kg drug dose
      at day 28 post-treatment. A significant decline in the relative percentage of
      primary spermatocytes (4C) was observed at day 7 that continued up to day 70 post
      treatment depending on the drug dose. Round spermatids (1C) declined
      significantly at day 21 post-treatment after administration of 0.25--2.0 mg/kg VM
      26. The relative percentage of elongated spermatids showed a significant decline
      at day 28 after 1 and 2 mg/kg drug treatment. These alterations in different germ
      cell populations are reflected in the various germ-cell ratios. The 4C:2C ratio
      showed a significant decline at day 7 and 14 post-treatment after 1 and 2 mg/kg
      VM-26 treatment, while the 1C:2C ratio declined significantly at day 21 post
      treatment in the mice treated with 0.5 and 2.0 mg/kg of VM-26. 4C:S-phase and
      1C:4C ratios increased significantly from day 1 to 70 post-treatment, depending
      on the drug dose. Our study demonstrates that the treatment of mice with low
      doses of VM-26 exerts cytotoxic effects on various germ-cell populations.

PMID- 11516527
TI  - Cell cycle was disturbed in the MNNG-induced initiation stage during in vitro two
      stage transformation of Balb/3T3 cells.
AB  - In vitro two-stage transformation, an important method for the screening of
      carcinogens, is a valuable approach for the mechanistic study of multi-stage
      carcinogenesis. However, very little is known about the molecular and cellular
      mechanisms, particularly in terms of cell cycle control during in vitro two-stage
      transformation. We improved the in vitro two-stage transformation method using N
      methyl-N'-nitro-N-nitrosoguanidine (MNNG) as an initiator and cadmium as a
      promoter, and reconfirmed the promotional effect of cadmium (Fang et al., 2001a).
      To determine the alterations of cell cycle control in the MNNG-induced initiation
      stage during transformation, we examined the effects of MNNG on Balb/3T3 A31 cell
      growth, and determined the alterations of the protein and/or mRNA levels of
      cyclins B1, D1, E, and G, PCNA, GADD45, p27, and wild-type p53. After 4 hour
      treatment of MNNG, populations of G2/M phase distribution and apoptotic fraction
      and the cyclin G mRNA level increased, while the cyclin B1 mRNA level decreased
      in a concentration-dependent manner. Wild-type p53, p27, and GADD45 protein
      levels also increased as a function of MNNG concentrations. However, cyclin D1,
      cyclin E, and PCNA expressions remained unchanged. During the initiation stage,
      PCNA protein expression decreased on the first day after MNNG-treatment, then
      increased gradually during the following 6 days, and further increased on the
      first day after cadmium treatment. Although wild-type p53 and p27 protein
      expressions also showed temporary retardation on the first day after MNNG
      treatment, the expressions increased gradually during the following 6 days, but
      decreased rapidly by the cadmium treatment. These results indicated that during
      the initiation stage, MNNG induced G2/M arrest and apoptosis with increased
      expressions of wild-type p53, p27, and GADD45 proteins; and down-regulated mRNA
      level of cyclin B1 and up-regulated mRNA level of cyclin G. In addition, although
      a few of the G2/M-arrested cells proliferated gradually, most cells continued to
      be suppressed and inactivated by the over-expressions of wild-type p53 and p27
      until the cadmium treatment.

PMID- 11516528
TI  - Detection of the effects of repeated dose combined propoxur and heavy metal
      exposure by measurement of certain toxicological, haematological and immune
      function parameters in rats.
AB  - In the present study, an immunotoxicity test system, containing general
      toxicological (body weight gain, organ weights), haematological (WBC,RBC, Ht,
      mean cell volume of the RBCs, cell content of the femoral bone marrow), and
      immune function (PFC assay, DTH reaction) investigations, was used for detection
      the effects of a 4 weeks repeated low dose combined oral exposure of male Wistar
      rats with propoxur and the heavy metals arsenic or mercury. Two doses of the
      compounds were used: a higher one (the lowest dose which resulted in significant
      change of at least one parameter examined in previous dose-effect experiments),
      and a lower one (the highest dose which proved to be non-effective). The applied
      doses were: 8.51 and 0.851 mg kg(-1) of propoxur, 13.3 and 3.33 mg kg(-1) of
      NaAsO(2), and 3.20 and 0.40 mg kg(-1) of HgCl(2). In the combination treatment,
      the high dose of propoxur was combined with the low dose of arsenic or mercury,
      and the high doses of each heavy metals were combined with the low dose of
      propoxur. The main finding of this study was that some of the combinations
      significantly altered the relative weight of liver, adrenals and kidneys, related
      to both the untreated and the high dose internal control. Among the immune
      functions examined, only the PFC content of the spleen showed a trend of changes
      in certain combinations versus the corresponding high dose control. According to
      the present results, combined exposure with propoxur and the heavy metals
      examined can modify the detection limit of the single compounds and/or may alter
      their toxic effects.

PMID- 11516529
TI  - Factors that modify penicillamine-induced autoimmunity in Brown Norway rats:
      failure of the Th1/Th2 paradigm.
AB  - Idiosyncratic drug reactions appear to be immune-mediated. Immune responses are
      driven by helper T cells (Th); Th1 responses promote cell-mediated immunity,
      whereas Th2 responses drive antibody-mediated reactions. Th1 cytokines inhibit
      Th2 responses and Th2 cytokines inhibit Th1 responses; therefore, it may be
      possible to prevent idiosyncratic drug reactions by changing the Th1/Th2 cytokine
      balance. We tested this hypothesis in an animal model in which penicillamine
      causes an autoimmune syndrome in Brown Norway rats. This syndrome has the
      hallmarks of a Th2-mediated response and we tried to inhibit it with a polymer of
      inosine and cytosine (poly I:C), a Th1 cytokine-inducer. However, we found that a
      single dose of poly I:C, given at the onset of penicillamine treatment,
      significantly increased both the incidence (100 vs. 60%) and accelerated the
      onset (30+/-4 vs. 39+/-5 days) of penicillamine-induced autoimmunity when
      compared with controls. To rule out other effects of poly I:C that might
      overshadow the induction of Th1 cytokines, we directly tested the effects of the
      prototypic Th1 cytokine, interferon-gamma. Although not as dramatic, interferon
      gamma-pretreatment also appeared to make the syndrome worse. Conversely, when we
      used misoprostol, a prostaglandin-E analog that inhibits Th1 cytokines, it
      completely protected the animals. Just one dose of misoprostol prior to
      initiation of penicillamine treatment was sufficient to provide this protection.
      The syndrome was also completely inhibited by aminoguanidine, an inhibitor of
      iNOS. These results, although dramatic, suggest that the effects of these agents
      were not mediated by their effects on Th1/Th2 balance, but rather by some other
      mechanism.

PMID- 11516530
TI  - Different levels of Schistosoma mansoni infection increased the mutagenicity of
      benzo(a)pyrene, the activity of aryl hydrocarbon hydroxylase and the formation of
      hepatic microsomal hydrogen peroxide.
AB  - The present study investigates the influence of different levels of Schistosoma
      mansoni infection (60, 120, 180, 300, 600 cercariae per mice) after 33 days on
      the activity of aryl hydrocarbon hydroxylase (AHH) and the formation of hepatic
      hydrogen peroxide (H(2)O(2)) during the metabolic activation of benzo(a)pyrene
      [B(a)p]. Also, it shows the mutagenic effect of B(a)p at different levels of S.
      mansoni infection using Salmonella typhimurium TA 98 and TA 102 as a tester
      strains. High levels of H(2)O(2) production (222 nmol/mg protein) and AHH
      activity (240 pmol 3-OH B(a)p per mg protein) were seen at 300 cercariae per
      mice. Increasing histidine revertant colonies at TA98 and TA102 were detected at
      different levels of S. mansoni infection. These data clearly demonstrate that S.
      mansoni infection changes the mutagenicity of B(a)p, AHH activity, as well as
      enhancing the formation of hepatic H(2)O(2) generated during the metabolic
      activation of B(a)p in infected mice.

PMID- 11516532
TI  - The role of high-resolution ultrasonography in management of calcific tendonitis
      of the rotator cuff.
AB  - This article predicts the possibility of resorption of the calcific plaques in
      the shoulder using high-resolution ultrasonography (HRUS) and color Doppler
      ultrasound (CDUS), and evaluates the therapeutic effect of US-guided fine-needle
      multiple punctures of the calcific plaque. A total of 100 patients with calcific
      tendenosis were divided into 3 groups: In group 1, patients having chronic
      shoulder pain received conservative treatment; in group 2, patients having acute
      exacerbation of shoulder pain also received conservative treatment; and group 3
      patients received US-guided fine-needle multiple punctures or aspiration. In
      CDUS, all images were classified as grade 0 (no color flow signals), grade 1
      (weak spotty color flow signal), grade 2 (few rod-like color flow signals), grade
      3 (many rod-like or linear color flow signals). In the follow-up study, marked
      improvement of patients' clinical condition with more than 50% size reduction of
      calcific plaque was defined as an effective treatment. There was no significant
      difference between group 1 and group 3 (p = 0.558) in CDUS, but there was a
      significant difference between group 1 and group 2 (p = 0.000), and group 2 and
      group 3 (p = 0.000) on the basis of classification of grade < 1 and grade > or =
      1. There was also significant difference in the follow-up result of effective
      management between group 1 and group 3 (p = 0.000), and group 1 and group 2 (p =
      0.000). In conclusion, HRUS with CDUS proved to be a good modality in evaluating
      the possibility of resorption of shoulder calcification and, if CDUS > or = grade
      1 in calcific tendonitis, we highly recommend conservative treatment with regular
      follow-up. On the other hand, if CDUS < grade 1, fine-needle repeated puncture
      could be considered as an effective alternative treatment.

PMID- 11516533
TI  - Three-dimensional ultrasonography in the diagnosis of rotator cuff lesions.
AB  - Two-dimensional (2-D) ultrasound (US) of rotator cuff lesions is a well
      established tool. The aim of this study was to elucidate if the use of 3-D
      sonography can increase the diagnostic yield of US. A total of 40 patients were
      preoperatively evaluated using 2-D and 3-D sonography, and these results were
      compared to intraoperative findings. Ultrasound was performed on a 530D US
      machine (Kretztechnik, Zipf, Austria) with a 10-MHz transducer. We found an
      increased validity of 3-D imaging, mainly based on the higher reliability in the
      diagnosis of partial-thickness cuff lesions. Sensitivity and specificity were
      found to be 91% and 82% for 3-D sonography and 74% and 82% for 2-D sonography,
      respectively. With 3-D US partial-tear rotator cuff lesions can be predicted more
      accurately.

PMID- 11516534
TI  - Validation of in vivo noninvasive high-frequency ultrasonography of the arterial
      wall layers.
AB  - To validate estimates of the arterial wall thickness and its separate layers, 19
      superficial (7 femoral and 12 cutaneous) arteries were transcutaneously
      sonographed in 13 anaesthetized pigs with a high-resolution equipment fitted with
      a 25 MHz frequency probe. Means of ultrasonographic estimates of each wall layer
      were compared with those obtained from microscopy of the respective arterial
      specimens taken after the pigs were sacrificed. For all vessels combined,
      Spearman-rank correlation tests between ultrasonography and histology estimates
      were significant for total arterial wall thickness (r(s) = 0.78; p =.0001) but
      not for the separate layers. For the cutaneous arteries, a significant
      correlation was found for total arterial wall thickness (r(s) = 0.69; p =.01) and
      media layer (r(s) = 0.76; p =.004). The method seems to give valid estimates of
      both total arterial wall and media thickness in superficial arteries, but to be
      less accurate for estimate the adventitia and intima layers.

PMID- 11516535
TI  - Unilateral vs. bilateral ultrasound in the monitoring of cerebral microemboli.
AB  - We used bilateral transcranial Doppler to monitor the number of microembolic
      events (ME) in the left and right middle cerebral arteries of 29 patients during
      cardiac surgery that required extracorporeal circulation. Based on a previously
      published study, we hypothesized that the commonly used method of doubling
      unilateral ME counts to obtain an estimated bihemispheric load would result in
      significant errors of estimation. In our sample, estimated bihemispheric counts
      were inaccurate by an average of 18% (range 0--80%). Despite this large range of
      error, calculation of Cronbach's alpha revealed that actual error due to
      unreliability (4%) was small relative to the large variation in ME counts across
      subjects in this patient series. These findings suggest that unilateral
      monitoring is sufficient when the goal is to characterize a given subject's ME
      load within the context of the other subjects in the sample. However, when
      precise ME counts are required, bilateral monitoring is essential.

PMID- 11516536
TI  - Tumor vascularization in experimental melanomas: correlation between unenhanced
      and contrast enhanced power Doppler imaging and histological grading.
AB  - The purpose of this study was to evaluate the reliability of unenhanced and
      enhanced power Doppler sonography in visualization of intratumoral
      angioneogenesis. Thirty-seven malignant melanomas, which had been implanted intra
      or subcutaneously in 22 mice, were examined. Various B-mode criteria, power
      Doppler criteria and spectral Doppler parameters were evaluated before and after
      IV-application of the d-galactose-based contrast agent Levovist. After
      sonographic examination, all tumors were analyzed histologically with
      semiquantitative grading of tumoral vascularization. Unenhanced, in 70% of the
      tumors, no intratumoral vessels were visible using power Doppler, but only in 11%
      of the intracutaneous and in 0% of the subcutaneous after injection of the
      contrast agent. The enhanced mode was definitely superior to unenhanced Doppler
      in showing the intratumoral vascularity. The intratumoral vascular structure
      could be sufficiently analyzed in 30% of all tumors by unenhanced Doppler, but in
      92% enhanced. The mean percentage vessel area increased about 433% after
      application of Levovist (intracutaneous: 485%, subcutaneous: 280%). Despite the
      missing direct correlation between the sonographically and histologically
      determined grade of tumor vascularization (Pearson's correlation unenhanced
      0,356, p <.05/enhanced 0.395, p <.05), the correlation between the percentage
      vessel area and the histologic grade of vascularization was improved after
      application of the contrast agent (Pearson's correlation unenhanced 0.347, p
      <.05/enhanced 0.686, p <.01). We did not find a significant direct correlation
      between histologically and sonographically determined degree of vascularization.
      However, the correlation was improved using a d-galactose-based signal-enhancing
      agent in power Doppler sonography.

PMID- 11516537
TI  - Quantitative regional analysis of myocardial wall motion.
AB  - This paper presents a new technique for semiautomatic quantification of regional
      heart function from 2-D echocardiography. It uses a novel left ventricular border
      tracking algorithm based on shape-space ideas that we have recently described. In
      this paper, we show how to decompose the tracked output into clinically
      meaningful segmental parameters (wall excursion and thickening), using what we
      call a computational interpretational space (CIS). This leads to a quantitative
      and automatic scoring scheme for endocardial excursion and myocardial thickening.
      The method is illustrated on data from a patient with a myocardial infarct in the
      apical anterior/inferior region of the heart and is also assessed in a small
      retrospective dobutamine stress echocardiography clinical case study.

PMID- 11516538
TI  - Assessment of the spatial homogeneity of artery dimension parameters with high
      frame rate 2-D B-mode.
AB  - To elicit vessel wall inhomogeneities in diameter and distension along an
      arterial segment, a 2-D vessel wall-tracking system based on fast B-mode has been
      developed. The frame rate of a 7.5-MHz linear-array transducer (length 36 mm) is
      enhanced by increasing the pulse-repetition frequency to 10 kHz, decreasing the
      number of echo lines per frame from 128 to 64, or increasing the interspacing
      between echo lines with a factor of two or four. Dedicated software has been
      developed to extract for each echo-line the end-diastolic diameter from the B
      mode image and the 2-D distension waveform from the underlying radiofrequency
      (RF) information. The method is validated in tubes with various focal lesion
      sizes. Straight segments of presumably homogeneous common carotid arteries have
      also been tested. The temporal and spatial SD of diameter or distension reveals
      inhomogeneities in time or space (i.e., inhomogeneities in artery
      characteristics). The method can be implemented in echo systems supporting high
      frame rates and real-time processing of radiofrequency data.

PMID- 11516539
TI  - Evaluation of a 1 MHz transducer for transcranial Doppler ultrasound including
      embolic signal detection.
AB  - A 1 MHz transducer for use with transcranial Doppler ultrasound may improve the
      intensity and therefore the detection of embolic signals (ES) and may also reduce
      the number of absent acoustic windows. A series of studies was performed to
      investigate its potential benefits. Firstly, ES were detected using a 1 MHz and a
      2 MHz transducer both in vitro and in vivo. Secondly, the time taken to identify
      100 middle cerebral arteries (MCA) was recorded for both transducers and the best
      Doppler signal obtained was reviewed off-line and graded for quality. ES were
      more intense when detected with the 1 MHz compared with the 2 MHz transducer,
      both in vitro (p <.0001) and in vivo (p <.0001). Of the 100 MCAs studied, 81 had
      acoustic windows identified with both transducers. The number of acoustic windows
      detected with one transducer but not the other was the same for both transducers
      (n = 3). The time taken to identify the MCA was longer with the 1 MHz transducer
      (p <.0001) and the quality of the signal achieved was poorer (p <.0001). In
      conclusion, the 1 MHz transducer improved embolic signal intensity but the
      overall quality of the flow spectrum obtained was poorer with the 1 MHz than with
      the 2 MHz transducer. A lower frequency transducer of 1 MHz or possibly 1.5 MHz
      with transcranial Doppler ultrasound may improve the application of embolic
      signal detection but may not improve the signal for routine measurement of flow
      velocities.

PMID- 11516540
TI  - New technique for emboli detection and discrimination based on nonlinear
      characteristics of gas bubbles.
AB  - Detection and characterization of emboli in the blood stream is of high clinical
      importance for making decisions after surgery. In this study, a new technique
      based on the nonlinear oscillations of gas bubbles was applied to gaseous emboli
      detection, characterization and sizing. To simulate gaseous emboli, an
      experimental system was developed to produce air bubbles of uniform diameters
      ranging from 19 microm up to 200 microm. The ultrasonic setup consisted of low
      frequency transducers operating at 130 kHz and 250 kHz and using low acoustic
      pressures (30 kPa and 55 kPa). The experimental and theoretical results show
      that, depending on the transmitted frequency and the bubble sizes, higher
      harmonic components were produced in the frequency spectrum of the backscattered
      echo. Nonresonating bubbles scatter either linearly when their sizes are far away
      from the resonance size or nonlinearly at the second or third harmonic frequency
      when their sizes are getting close to the resonance size. Only resonant bubbles
      or bubbles very close to the resonance size are able to scatter at higher
      harmonic frequencies (fourth and fifth). This property is used to discriminate
      resonating bubbles from other bubble sizes. The appearance of harmonic component
      in the frequency spectrum seems to be an unambiguous tool to differentiate
      gaseous emboli from solid emboli that scatter linearly.

PMID- 11516541
TI  - B-scan ultrasound imaging of thermal coagulation in bovine liver: frequency shift
      attenuation mapping.
AB  - Thermal therapy is an experimental procedure to treat localised tumours in, for
      example, the prostate, liver, kidney or breast. Following work that demonstrated
      a marked increase in the ultrasound (US) attenuation of tissues heated above 65
      degrees C, US attenuation estimation is proposed as a method to monitor the
      progression and extent of thermal therapy. In this study, B-scan attenuation
      mapping techniques, based on the shift in centre frequency of the US signal, are
      examined. A simple technique based on the change of phase of the quadrature
      demodulated signal is presented and analysed. Autoregressive analysis is also
      examined. It is shown with simulated data that these methods are effective at
      differentiating and localizing the attenuation change associated with tissue
      coagulation, but that, in the analysis of phantom or ex vivo bovine liver data,
      electronic noise severely limits the effectiveness of these techniques.

PMID- 11516542
TI  - Phase aberration effects in elastography.
AB  - In sonography, phase aberration plays a role in the corruption of sonograms.
      Phase aberration does not have a significant impact on elastography, if
      statistically similar phase errors are present in both the pre- and
      postcompression signals. However, if the phase errors are present in only one of
      the pre- or postcompression signal pairs, the precision of the strain estimation
      process will be reduced. In some cases, increased phase errors may occur only in
      the postcompression signal due to changes in the tissue structure with the
      applied compression. Phase-aberration effects increase with applied strain and
      may be viewed as an image quality derating factor, much like frequency-dependent
      attenuation or undesired lateral tissue motion. In this paper, we present a
      theoretical and simulation study of the effects of phase aberration on the
      elastographic strain-estimation process, using the strain filter approach.

PMID- 11516543
TI  - Temporal and spatial evaluation of lesion reparative responses following
      superthreshold exposure of rat lung to pulsed ultrasound.
AB  - This study characterized the reparative responses in rat lung. Forty-five adult
      female rats were exposed at two sites over the left lung to 3.1-MHz
      superthreshold pulsed ultrasound. The repair of lung lesions was evaluated from 0
      through 44 days postexposure. Macroscopic lesions at 0 days postexposure were
      large bright red ellipses of hemorrhage. By 1 and 3 days postexposure, lesions
      were the same size and dark red to red-black, but, by 3 days postexposure,
      lesions had a raised surface appearance. From 5 to 10 days postexposure, lesions
      grew smaller in size, progressed from red-gray to yellow-brown, and retained a
      raised surface appearance. From 13 through 44 days postexposure, lesions
      gradually decreased in size, had a faint yellow-brown discoloration, and
      gradually lost the raised surface appearance. By 37 and 44 days postexposure,
      lung returned to near normal morphology, but had small areas of light yellow
      brown discoloration in the areas where lung was exposed. Microscopic lesions at 0
      and 1 days postexposure were areas of acute alveolar hemorrhage. By 3 days
      postexposure, lesions had loss of alveolar erythrocytes and the formation of
      hemoglobin crystals. From 5 through 44 days postexposure, iron in degraded
      erythrocytes was processed to hemosiderin and was negligible in quantity at 44
      days postexposure. The proliferation of resident cells (likely alveolar
      epithelial cells, fibroblasts and endothelial cells) and the infiltration of
      inflammatory cells in lesions declined in intensity as the lesions aged and was
      minimal by 44 days postexposure. Under the superthreshold exposure conditions
      described, lesions induced by ultrasound do not seem to have long-term residual
      effects in lung.

PMID- 11516544
TI  - Sonoluminescence as an indicator of cell membrane disruption by acoustic
      cavitation.
AB  - Ultrasound (US) has been shown to transiently disrupt cell membranes and,
      thereby, facilitate the loading of drugs and genes into viable cells. Because
      these effects are believed to be mediated by cavitation, we hypothesized that
      measured levels of cavitation-induced sonoluminescence should correlate with
      levels of US bioeffects. We, therefore, quantified the number of calcein
      molecules delivered and the loss of viability in prostate cancer cells exposed to
      24-kHz US over a range of different pulse lengths (1 to 100 ms), total exposure
      times (0.1 to 10 s) and pressures (1.0 to 9.8 atm). Consistent with previous
      observations, uptake increased and viability decreased with increasing pulse
      length, total exposure time and pressure. As a new observation, we established
      correlations between the amount of light produced by sonoluminescence and both
      molecular uptake and cell viability. These results support a cavitation-based
      mechanism for these bioeffects and suggest a means to control US effects on cells
      using sonoluminescence-based feedback.

PMID- 11516545
TI  - EPR analysis of radicals generated in ultrasound-assisted lipoplasty simulated
      environment.
AB  - The generation of various radicals by application of continuous wave (CW) high
      intensity ultrasound energy (HIUE) to an aqueous biologic medium containing spin
      traps, under conditions simulating ultrasound-assisted lipoplasty (UAL), was
      demonstrated by EPR spectroscopy. The addition of water- soluble antioxidants,
      ascorbic acid and glutathione to the wetting solution substantially reduces the
      levels of hydroxyl radicals in the sonicated medium. These findings provide
      direct evidence for the generation of cavitation in the simulated intercellular
      environment, corroborating previous data, and pointing out that generation of
      transient cavitation in clinical UAL and other therapeutic and surgical
      applications of ultrasound is possible. The findings indicate that the effect of
      transient cavitation in aqueous biologic media may be similar to the effects of
      ionizing radiation, and raise the question of the long-term biosafety of the use
      of CW HIUE in UAL. The introduction of biocompatible water-soluble antioxidants
      to the sonicated medium may be utilized to suppress accumulation of radicals and
      reduce their possible adverse effects.

PMID- 11516546
TI  - Bone material ultrasound velocity is predictive of whole bone strength.
AB  - In humans, bone strength is assessed indirectly by the noninvasive measurement of
      structure or mass. Recent clinical application of an ultrasonic critical-angle
      reflectometry technique (UCR) has demonstrated the measurement of the regional
      and directional distribution of mechanical stiffness. This study investigates the
      specific question: are these measurements of a local material level property
      predictive of the strength of whole bone? Maximum values of pressure wave
      velocity and breaking strength were recorded at two locations (midshaft and base
      of neck) on rat femurs from growing rats. The results demonstrate a strong
      empirical relationship between material-level ultrasound (US) velocity and whole
      bone mechanical strength. However, the US velocity at a specific bone site can be
      used to assess bone strength at that site only, explaining discrepancies in other
      published studies that negate a relationship between strength and US velocity.
      The results indicate an important role for US velocity measurement in clinical
      evaluation of bone health.

PMID- 11516547
TI  - Follow-up of 13 patients with surgical treatment of cerebral cavernous
      malformations: effect on epilepsy and patient disability.
AB  - OBJECTIVE: We report a series of 13 patients with surgical treatment of cerebral
      cavernous malformation (CM). The aim of this study was to investigate
      postoperative patient disability and seizure control in patients with CM in order
      to clarify indications for neurosurgical removal. In our series we emphasize the
      beneficial effect of excision of CMs. We also give an overview of the current
      literature covering options for treatment in surgically inaccessible CMs.
      METHODS: In this retrospective study we describe the clinical outcomes of
      neurosurgical intervention in 13 patients with a CM. Seven patients had epilepsy
      at presentation and six had focal neurological deficits due to intracerebral
      haemorrhage (five patients) or mass effect due to the CM (one patient). The
      modified Rankin scale was used to define patient disability pre- and
      postoperatively. An overview of the indications for surgery and postoperative
      outcome with follow up periods of 1-6 years (mean: 3.3 years) are provided.
      RESULTS: In all patients presenting with epilepsy a reduction in seizure
      frequency was seen. Four of them became seizure-free postoperatively. The six
      patients with neurological deficits due to intracerebral haemorrhage or mass
      effect due to the CM showed clinical improvement postoperatively, two of them
      made full recoveries. Improvement of the postoperative Rankin score was seen in
      six of 13 patients. CONCLUSION: Improvement in seizure control and reduction in
      patient disability warrants surgical intervention in symptomatic CMs.

PMID- 11516548
TI  - Intra-operative electromyographic monitoring of the lower cranial motor nerves
      (LCN IX-XII) in skull base surgery.
AB  - The functional preservation of lower (motor) cranial nerves (LCN) is endangered
      during skull base surgery. Intra-operative EMG monitoring of the LCN IX-XII was
      investigated in 78 patients undergoing 80 operations on various skull base tumors
      with regard to technical feasibility and clinical efficacy. Ongoing 'spontaneous
      muscle activity' (SMA) and 'compound muscle action potentials' (CMAP) following
      supramaximal bipolar stimulation were intra-operatively recorded applying needle
      electrodes into the soft palate (CN IX: n=76), the vocal cord (CN X: n=72), the
      trapezius muscle (CN XI: n=18), and the tongue (CN XII: n=71). From 24/22/8 cases
      with LCN IX/X/XII deficits (despite monitoring) only 5/6/4 remained unchanged (3
      6 months postoperative). An irreversible plegia of the LCN IX/X/XII occurred in
      three (1/1/1) patients. In 7/6/1 patients postoperative (3-6 months) LCN IX/X/XII
      function was better than preoperatively. In all patients accessory nerve function
      remained unchanged. 'Pathological' SMA of the LCN IX/X/XII occurred in 12/16/8
      cases, but in only 6/5/3 cases corresponded to postoperative LCN deficits.
      Corresponding 'pathological' SMA patterns were found in 18/17/5 out of 24/22/8
      cases with postoperative LCN IX/X/XII dysfunction. Reproducible CMAP of LCN
      IX/X/XI/XII could be recorded in 59/56/11/32 patients. Approximate 'normal'
      values were calculated and compared to (very few) data so far given in the
      literature. Electromyographic monitoring proved to be a safe tool for the intra
      operative identification and localization of the LCN contributing to their
      anatomical and functional preservation. The predictive value of standard
      neurophysiological parameters for functional outcome, however, is limited.

PMID- 11516549
TI  - Non-traumatic cerebrospinal fluid rhinorrhea indirectly caused by remote brain
      tumor: a case report and review of the literature.
AB  - Non-traumatic cerebrospinal fluid rhinorrhea indirectly caused by a remote brain
      tumor has rarely been reported. Here we describe a case of non-traumatic
      cerebrospinal fluid rhinorrhea that occurred as the initial symptom of a
      posterior falx meningioma. In addition, based on the period of occurrence of
      cerebrospinal fluid rhinorrhea before or after the tumor operation, we introduced
      a novel classification for these cases into pre-treatment and post-treatment
      types. The findings of the present case and the results of our literature
      research suggest that different treatments should be used for patients with these
      two types of non-traumatic cerebrospinal fluid rhinorrhea resulting from remote
      brain tumor. After tumor excision, patients of the pre-treatment type may receive
      conservative management or cerebrospinal fluid shunting, while patients of the
      post-treatment type need direct repair of the fistula.

PMID- 11516550
TI  - Respiratory monitoring in neuromuscular disease - capnography as an additional
      tool?
AB  - Daytime complaints like fatigue, sleepiness and cognitive dysfunction in
      neuromuscular disease can be due to nocturnal hypercapnia and hypoxemia. Daytime
      respiratory diagnostics does not reflect sleep disordered breathing. Nocturnal
      pulse oxymetry and capnography were performed in 11 patients (15-75 years old)
      with different slowly progressive neuromuscular diseases. Only four patients
      complained of dyspnea. Pulmonary function was abnormal in three patients. Blood
      gas samples showed a hypoxemia in three patients. Pulse oxymetry results were
      pathological in six patients. Nine patients presented abnormal capnographies.
      According to these results either nocturnal oxygen application was initiated or
      ventilatory parameters were modified. Daytime symptoms and muscular strength
      improved markedly. Capnography and pulse oxymetry should be performed during the
      course of neuromuscular disease to detect respiratory insufficiency. Capnography
      seems to be a more sensitive indicator for respiratory impairment especially when
      artificial ventilation has been initiated.

PMID- 11516551
TI  - Twenty-nine years after carbon monoxide intoxication.
AB  - Carbon monoxide (CO) is a worldwide environmental toxin and a leading cause of
      deliberate or accidental poisoning. There is an extensive literature devoted to
      the clinical features and treatment of those victims who have survived acute CO
      poisoning for a short length of time. The long-term sequelae of non-fatal
      poisoning have received scanty references, and the prospects for the long-lasting
      survivors of acute CO intoxication are less clear. Literature review uncovered
      reports of only three patients who were followed for a considerable period of
      time. We present a case of CO poisoning with progressive neurological and
      psychological deterioration that began 17 years after recovery from a severe,
      accidental CO asphyxia. The patient was examined in the neurology out patient
      clinic 29 years after the initial CO intoxication. We believe the unique status
      of this patient, her similarity to one other case in the literature and the
      circumstances allowing correlation of the clinical picture to the CO poisoning
      warrants emphasis.

PMID- 11516552
TI  - Clinical features of symptomatic Rathke's cleft cyst.
AB  - To investigate the clinical features of Rathke's cleft cysts (RCCs), we
      retrospectively analyzed 15 cases with histologically confirmed RCCs. All
      patients underwent formal testing of visual field, endocrinological evaluation
      and magnetic resonance imagings. As overall presenting symptoms, endocrine
      disturbance was the most common symptoms, followed by visual disturbance and
      headache. Among the endocrine disturbances based on adenohypophysial dysfunction,
      hyperprolactinemia was most common. Considering the size of RCCs, RCCs could
      induce hyperprolactinemia only when the cysts became large enough to compress the
      infundibular system. Our series showed relative high incidence of pituitary
      dwarfism and diabetes insipidus (DI). These facts indicated that RCCs could evoke
      hyposecretion of growth hormone in young patients and DI in aged patients by
      direct compression of the pituitary gland in the early stage of progression. All
      cases who had headache had no other symptoms. We could not prove the evidence
      that RCCs could induce headaches in these cases. This might be suggested that
      headache could not be a sole symptom in cases of RCCs.

PMID- 11516553
TI  - MR imaging of cavernous sinus invasion by mucormycosis: a case study.
AB  - Cavernous sinus thrombosis is a serious condition, which, if not recognized
      early, can lead to a fulminant course. Knowledge of risk factors along with early
      recognition of signs and symptoms may alter the course of this condition. We
      present a case of a patient with cavernous sinus thrombosis with characteristic
      findings on MRI. Biopsy of the sinuses revealed mucromycosis as the offending
      agent.

PMID- 11516554
TI  - Lhermitte-Duclos disease (Dysplastic gangliocytoma of the cerebellum).
AB  - OBJECTIVE: Dysplastic gangliocytoma of the cerebellum (Lhermitte-Duclos disease)
      is a rare hamartomatous lesion of the cerebellar cortex. The pathogenesis of the
      disease is still poorly understood. Lhermitte-Duclos disease was recently
      considered to be part of a multiple hamartoma-neoplasia syndrome (Cowden
      disease). We add two further cases to this rare entity. PATIENTS: A 24-year old
      woman presented with occipital headaches, blurred vision, diplopia and ataxia of
      gait. Physical examination revealed turricephaly. The second patient was a 37
      year old woman, who presented with progressive occipital headache with nausea and
      vomiting. Physical examination revealed congenital facial asymmetry. Computed
      tomography and NMR-imaging, respectively demonstrated a space occupying mass of a
      cerebellar hemisphere in both cases. RESULTS: Suboccipital craniotomy and
      complete removal of the infratentorial tumour were performed in both patients.
      Histopathological findings clinched the diagnosis of Lhermitte-Duclos disease.
      Postoperative course was uneventful in the first and complicated by progressive
      occlusive hydrocephalus in the second patient, necessitating permanent surgical
      shunt drainage. Both patients were discharged free of complaints. CONCLUSIONS:
      Dysplastic cerebellar gangliocytoma is commonly associated with progressive mass
      effects in the posterior fossa and typically presents with headaches, cerebellar
      dysfunction, occlusive hydrocephalus and cranial nerve palsies. The disease
      usually manifests in young adults, but the age at presentation ranges from birth
      to the sixth decade. There is no sex predilection. NMR-imaging became a useful
      clue to the diagnosis within the last decade. Therapy consists of decompression
      of the posterior fossa by total surgical removal of the tumour mass.

PMID- 11516555
TI  - Mutism after posterior fossa surgery. Review of the literature.
AB  - Mutism is an infrequent and transitory complication observed following posterior
      fossa surgery. Patients become mute in the immediate postoperative period, with
      restoration of speech within a few weeks. A review of the literature disclosed
      157 patients with this condition. The anatomical structures thought to be
      involved are the connections between the cerebella dentate nucleous, the
      ventrolateral nucleous of the contalateral thalamus and the supplementary motor
      area. We reviewed 157 of cerebellar mutism; however several reports did not give
      sufficient information about the patients and 134 cases were selected for this
      study. The ages of the patients ranged from 2 to 61 years and the vermisat was
      the site of the tumour in 89% of the cases. All tumours were considered to be
      large or very large. The mutism lasted from 4 days to 52 months and was transient
      in all cases.

PMID- 11516556
TI  - Posterior cortical atrophy. Two case reports and a review of the literature.
AB  - We present two cases of progressive early-onset dementia with apraxia and
      visuospatial disability as initial manifestations. In the later stages of the
      illness Gerstmann's and Balint's syndromes developed. Structural neuroimaging
      demonstrated parieto-occipital atrophy and functional imaging revealed bilateral
      hypometabolism and hypoperfusion in these areas. These cases fulfil the
      diagnostic criteria of posterior cortical atrophy (PCA). Frontal lobe involvement
      became evident as the disease progressed. Alzheimer's disease also typically
      features this anterior spread and possibly this is the underlying pathological
      substrate for this clinical syndrome, although definite pathology is lacking. In
      this report, we describe longitudinal evolution in these two cases of PCA.

PMID- 11516557
TI  - Multiple spinal intramedullary cavernous angioma: case report.
AB  - Spinal cavernous angiomas frequently accompany to cranial cavernous angiomas.
      Multiple spinal cord cavernous angiomas are very rare and to authors knowledge,
      only one case has been described having multiple intramedullary cavernous
      angiomas without cranial involvement until now. In this report, we present a case
      with acute paraplegia who had thoracic and cervical intramedullary cavernous
      angiomas and normal cranial magnetic resonance imaging.

PMID- 11516558
TI  - Aphemia: an isolated disorder of articulation.
AB  - Aphemia is a disorder with prominent speech abnormality. Since its description by
      Broca, there has been debate regarding the neuropsychological disorganization
      underlying aphemia: is aphemia an articulatory disorder or a language disorder?
      We describe a patient with markedly impaired articulation, but preserved
      receptive and written language function and buccal-facial coordination. The
      location of his stroke was in the left precentral gyrus, undercutting a small
      area of motor and premotor cortex. This case suggests that aphemia can occur as
      an isolated articulation deficit without language involvement or more widespread
      bulbar apraxia, and may be a severe form of apraxia of speech.

PMID- 11516560
TI  - Developmental changes in 5-hydroxytryptamine-induced rhythmic activity in the
      spinal cord of rat fetuses in vitro.
AB  - The roles played by glycine- and glutamate-mediated synaptic transmission in the
      generation of 5-hydroxytryptamine (5-HT)-induced rhythmic activity were examined
      in isolated spinal cord preparations from fetal rats. Bath application of 5-HT
      (0.1-30 microM) evoked rhythmic activity in lumbar ventral roots at and after
      E14.5. Bath application of strychnine (5 microM), a glycine-receptor antagonist,
      reduced the frequency of the rhythmic activity to 37% of control at E14.5.
      Although, kynurenate (4 mM), a glutamate-receptor antagonist, had little effect
      at this stage, it completely abolished the 5-HT-induced rhythmic activity at and
      after E18.5, when strychnine had little effect on the frequency. These results
      indicate that, at and shortly after its onset, the rhythmic activity is driven
      mainly by glycinergic rather than glutamatergic excitatory synaptic inputs, but
      that the latter become dominant later on.

PMID- 11516561
TI  - Modulation by age and gender of risk for Alzheimer's disease and vascular
      dementia associated with the apolipoprotein E-epsilon4 allele in Latin Americans:
      findings from the Maracaibo Aging Study.
AB  - An ongoing longitudinal study in Maracaibo, Venezuela, examined the interaction
      between apolipoprotein E (APOE) genotypes and Alzheimer's disease (AD) and
      vascular dementia (VD), evaluating age and gender as potential modifiers of risk.
      Overall, carriers of at least one epsilon4 allele were at higher risk for AD, not
      for VD; however, the risk was significant only for subjects older than 65, and it
      increased 10-fold in subjects older than 85. The risk of AD conferred by APOE
      epsilon4, adjusted for age and stratified by gender, was significant only for
      women. No association was found between the epsilon-2 allele and AD or VD. The
      results support the notions that APOE-epsilon4 is relevant for late-onset, not
      early onset AD, and that age and gender act as modulators of this association.

PMID- 11516562
TI  - Three novel alternatively spliced isoforms of the human beta-site amyloid
      precursor protein cleaving enzyme (BACE) and their effect on amyloid beta-peptide
      production.
AB  - Three novel alternatively spliced transcripts of the beta-site amyloid precursor
      protein cleaving enzyme (BACE) were cloned from human brain. Alternative splicing
      of the RNA occurs at an internal donor in exon 3 and/or an internal acceptor in
      exon 4. The splicing events lead to a deletion of 25 (BACE-I-476), 44 (BACE-I
      457) and 69 (BACE-I-432) amino acids and the latter two caused the loss of two of
      four N-linked glycosylation sites. Although the mature form of BACE-501 was
      resistant to endoglycosidase H treatment, glycosylated forms of BACE-I-457 and
      BACE-I-476 were sensitive. This result suggests that BACE-I-457 and BACE-I-476
      underwent different post-translational modifications. Moreover, the beta
      secretase activity of BACE-I-457 and BACE-I-476 was significantly weaker than
      that of BACE-501. Thus, these isoforms may contribute to a physiological function
      of BACE.

PMID- 11516563
TI  - Priming stimulation of group II metabotropic glutamate receptors inhibits the
      subsequent induction of rat hippocampal long-term depression in vitro.
AB  - The ability of priming activation of metabotropic glutamate receptors (mGluRs) to
      regulate long-term depression (LTD) was studied in area CA1 of hippocampal slices
      taken from young adult male rats. Pharmacological activation of Group I mGluRs 30
      40 min prior to low-frequency stimulation at 3 Hz failed to affect LTD.
      Activation of Group II mGluRs, however, significantly inhibited the LTD by >50%,
      while activation of Group III mGluRs had no statistically significant effect on
      LTD. The inhibition of LTD by activation of Group II mGluRs was even stronger
      when the Group II agonist was applied during the low-frequency stimulation.
      Because activation of Group II mGluRs is also known to inhibit LTP, the net
      effect of such stimulation is the induction of a metaplasticity that greatly
      restricts the effective range of stimuli that can evoke synaptic plasticity in
      the hippocampus.

PMID- 11516564
TI  - Continual replacement of newly-generated olfactory neurons in adult rats.
AB  - It has been known that stem cells do exist in the central nervous system, and
      adult neurogenesis is continually taking place in the olfactory bulb during life.
      We report here, with the combined method of autoradiography using (3)H-thymidine
      and immunohistochemistry for a neuronal marker, that 65.3-76.9% of calretinin
      immunoreactive bulbar neurons are replaced during the short period of 6 weeks in
      the adult rodent. The results indicate that neuronal replacement is a common
      phenomenon in the olfactory bulb during life.

PMID- 11516565
TI  - Pre- and postnatal expression of brain-derived neurotrophic factor mRNA/protein
      and tyrosine protein kinase receptor B mRNA in the mouse hippocampus.
AB  - Brain-derived neurotrophic factor (BDNF) is implicated in the control of
      hippocampal development. In this study, we have analyzed the developmental
      expression of BDNF mRNA/protein and its receptor tyrosine protein kinase receptor
      (trk) B mRNA in the mouse hippocampus by competitive reverse
      transcription/polymerase chain reaction and enzyme-linked immunoassay. Cell-type
      specificity of BDNF/trkB expression was studied in primary hippocampal cultures.
      BDNF levels increased stepwise from embryonic day 15 until the second postnatal
      week, whereas trkB expression was stable throughout development. Neurons and
      astrocytes expressed both BDNF and trkB. Our data suggest that developmental BDNF
      action mainly occurs postnatally and indicates that hippocampal neurons and
      astroglia not only produce BDNF but also appear to be targets for BDNF.

PMID- 11516566
TI  - Bradykinin antagonist decreases early disruption of the blood-spinal cord barrier
      after spinal cord injury in mice.
AB  - Bradykinin is one of the key molecules involved in the disruption of the blood
      brain barrier and blood-spinal cord barrier occurring after spinal cord injury
      (SCI). Previously we have shown a biphasic opening of the blood-spinal cord
      barrier as well as increased transport of tumor necrosis factor-alpha (TNFalpha)
      after SCI by compression of the lumbar spinal cord in mice. To evaluate the role
      of bradykinin in the two phases of blood-spinal cord barrier disruption, we
      pretreated mice with a potent bradykinin antagonist, the decapeptide B9430,
      before SCI. Our results show that B9430 decreased the general blood-spinal cord
      barrier disruption occurring immediately after SCI but failed to affect the
      delayed opening of the blood-spinal cord barrier observed 72 h after SCI. By
      contrast, the entry of TNFalpha after SCI was not affected by B9430 treatment. We
      conclude that bradykinin is involved in the early phase of blood-spinal cord
      barrier disruption, with B9430 non-selectively blocking this early disruption
      without affecting the selective transport system for TNFalpha. This indicates the
      therapeutic potential of bradykinin antagonists in ameliorating tissue damage
      induced by SCI.

PMID- 11516567
TI  - Protection of outer hair cells from reperfusion injury by an iron chelator and a
      nitric oxide synthase inhibitor in the guinea pig cochlea.
AB  - To examine whether an active process of the cochlea was injured by ischemia
      reperfusion, time courses of distortion-product otoacoustic emissions (DPOAEs)
      were examined before, during and after 30 min cochlear ischemia using albino
      guinea pigs. DPOAEs decreased to the minimum level when the animals were
      subjected to ischemia. When the cochlea was recirculated, DPOAEs initially
      recovered with time until 20 min after the onset of reperfusion. However,
      thereafter the amplitude of DPOAEs gradually decreased toward the noise level.
      Administration of deferoxamine (an iron chelator) or N-nitro-L-arginine (a nitric
      oxide synthase inhibitor) ameliorated this decrease of DPOAEs during reperfusion
      and significantly increased the DPOAE amplitudes 60 min after the onset of
      reperfusion as compared with those in non-treated animals. These results suggest
      that cochlear reperfusion as well as ischemia injured the active process of the
      cochlea and that free radicals and nitric oxide play important roles in this
      injury.

PMID- 11516568
TI  - Endurance training effects on 5-HT(1B) receptors mRNA expression in cerebellum,
      striatum, frontal cortex and hippocampus of rats.
AB  - The 5-HT(1B) receptors are the predominant auto- and heteroreceptors located on
      serotonergic and non-serotonergic terminals where they regulate the neuronal
      release of neurotransmitters. The present study investigated the effects of a 7
      week period of physical training on the expression of cerebral 5-HT(1B) receptors
      by measuring corresponding mRNA levels in rat. Using RNase protection assay
      technique, we have observed no change in 5-HT(1B) receptor mRNA levels in the
      striatum and in the hippocampus after moderate as well as after intensive
      training. In contrast, a significant decrease in 5-HT(1B) receptor mRNA levels
      was observed in cerebellum of intensively trained rats. Moreover, in frontal
      cortex, a significant decrease in 5-HT(1B) receptors mRNA level occurred in both
      groups of trained rats. These data suggest the existence of regional differences
      in the effect of physical exercise on the expression of 5-HT(1B) receptors.

PMID- 11516569
TI  - Potentiation of 5-HT(3) receptor functions in the hippocampal CA1 region of rats
      following repeated electroconvulsive shock treatments.
AB  - Modulation of serotonin (5-HT)(3)-receptor function by repeated electroconvulsive
      shock (ECS) treatment was investigated to elucidate the mechanism underlying the
      effectiveness of electroconvulsive therapy (ECT) which is clinically used for
      drug-resistant depression. ECS (100 V, 1 s) was applied once a day for 14 days
      via an electrode placed on the ears of rats (ECS group). For controls, rats were
      handled similar to the ECS-treated group except for the stimulation. Hippocampal
      slices (thickness, 450 microm) were prepared 24 h after the final ECS treatment
      when rats were 5-6 weeks old. Intracellular recordings were made from the neurons
      in the CA1 pyramidal cell layer. Activation of 5-HT(3) receptors increased
      spontaneous postsynaptic potentials (sPSP). Increased sPSP was mainly mediated by
      GABA. The 5-HT(3) receptor mediated increase in sPSP was potentiated in the ECS
      group compared with the control group. These findings suggest that the 5-HT(3)
      receptor function is potentiated by repeated ECS.

PMID- 11516570
TI  - Noradrenergic modulation of human cortex excitability by the presynaptic alpha(2)
      antagonist yohimbine.
AB  - The objective of this study was to determine if yohimbine, a central
      norepinephrine enhancing drug, increases cortico-motoneuronal excitability in
      intact humans. Transcranial magnetic stimulation was used to assess excitability
      of the motor system reflected in the parameters motor threshold, recruitment
      curve, intracortical inhibition and intracortical facilitation before and after
      oral administration of 20 and 40 mg yohimbine. Oral intake of 40 but not 20 mg
      yohimbine increased slope and plateau of the recruitment curve and intracortical
      facilitation. Motor threshold and intracortical inhibition remained unchanged.
      The data show that pharmacological enhancement of central norepinephrine in
      humans is effective to increase the cortico-motoneuronal excitability. Since
      cortical excitability is closely linked to neuroplasticity, this observation
      might be of possible relevance for strategies to enhance rehabilitative processes
      after cortical lesions by pairing noradrenergic drugs with motor training.

PMID- 11516571
TI  - Chronic treatment with certain antipsychotic drugs preserves upregulation of
      regulator of G-protein signalling 2 mRNA in rat striatum as opposed to c-fos
      mRNA.
AB  - Quantitative in situ hybridization on rat coronal brain sections with
      radiolabelled oligonucleotide probes was performed to investigate the effects of
      antipsychotic drugs on mRNA levels of regulator of G-protein signalling (RGS) 2
      and c-fos. This study demonstrated a similar increase of RGS2 mRNA level in the
      striatum upon both a single and a 21-day treatment with either haloperidol (2
      mg/kg) or risperidone (7.5 mg/kg) in contrast to clozapine (20 mg/kg). Otherwise,
      the acute c-fos mRNA induction in the striatum was abolished by 74 to 89% upon
      chronic treatment with either haloperidol or risperidone. In conclusion, the
      induction of RGS2 mRNA in the striatum, in contrast to the immediate early gene c
      fos mRNA, is preserved upon chronic treatment with haloperidol and risperidone.

PMID- 11516572
TI  - Distinction of different fingers by the frequency of stimulus induced beta
      oscillations in the human EEG.
AB  - Induced beta oscillations were studied in three normal subjects after mechanical
      stimulation of each fingertip of the right hand. For stimulation short tactile
      stimuli of 10 ms duration were presented at intervals of 4 s. The
      electroencephalogram was recorded with 60 closely spaced electrodes and sampled
      at 256 Hz. For each subject the reactive beta band was determined by comparing 1
      s power spectra. The largest beta power increase was found in the range of 12-28
      Hz on electrodes overlying the left-hand area. The Matching Pursuit algorithm was
      applied to single trials data and the frequency of single "atoms" determined. In
      one subject the little finger showed a significant higher frequency as compared
      to the thumb. The difference in frequency was in the order of 1 Hz.

PMID- 11516573
TI  - High-voltage-activated Ca2+ currents and the excitability of pyramidal neurons in
      the hippocampal CA3 subfield in rats depend on corticosterone and time of day.
AB  - This study tested the time-of-day dependence of the intrinsic postsynaptic
      properties of hippocampal CA3 pyramidal neurons. High-voltage-activated Ca2+
      currents and the Ca(2+)- and voltage-dependent afterhyperpolarizations were
      examined in slices of rat brains obtained at four distinct time periods. Just
      after onset of the dark phase, the steady-state amplitude of the Ca2+ current (
      1.24+/-0.11 nA) was significantly greater (P<0.03) than that of the light phase (
      0.84+/-0.06 nA). Over the entire time range, the amplitude of the Ca2+ current
      correlated with plasma corticosterone levels in a U-shaped function. Furthermore,
      depolarization-induced excitability during the dark phase exhibited an increased
      spike after depolarization (3.1+/-0.1 mV) and a slower adaptation of the firing
      frequency (146+/-18%). These findings point to a dynamic time-of-day dependence
      of the CA3 neuronal properties and postsynaptic Ca2+ currents.

PMID- 11516576
TI  - The history of Italian parasitology.
AB  - The history of Italian parasitology can be subdivided into two periods: pre-Redi
      and post-Redi. The first period includes the contributions to parasitology by
      savants who operated during the Roman, medieval and Renaissance eras; the second
      period started in 1668 when Francesco Redi published his experiments to debunk
      the theory of spontaneous generation; the work of Redi was subsequently continued
      by Vallisnieri, Spallanzani and others. The latter period includes classic
      contributions in the field of parasitology provided by veterinarians such as
      Ercolani, Perroncito, Piana and Rivolta, and by physicians such as Bassi, Grassi,
      Golgi, and Celli. Also, two outstanding pages of medical parasitology were
      written during this period--the unraveling and defeat of St. Gotthard's disease
      and the conquering of malaria on Italian soil--both accomplished through the
      generous efforts of dedicated individuals.

PMID- 11516574
TI  - Melatonin reduces anxiety induced by lipopolysaccharide in the rat.
AB  - In male Sprague-Dawley rats intraperitoneal (i.p.) injection of Escherichia coli
      lipopolysaccharide (0.25, 0.50 and 1 mg/kg) increased anxiety levels. This effect
      was reversed by a prior, concomitant, and subsequent i.p. treatment with
      melatonin (4 and 6 mg/kg). As the effects of melatonin upon the actions induced
      by lipopolysaccharide were reversed by the melatonin receptor antagonist
      luzindole (30 and 60 mg/kg, i.p.), we argued that they are, but not only,
      melatonin receptor mediated. These findings, in accordance with our previous
      works, suggest that melatonin could be useful in the treatment of sickness
      behaviour associated with systemic infection diseases or as adjuvant in the anti
      anxiety therapy.

PMID- 11516577
TI  - The future of veterinary parasitology.
AB  - Current evidence suggests research in veterinary parasitology is in decline
      despite its importance. This is particularly true in the UK where research funds
      have been diverted into BSE. Decline in interest in veterinary parasitology is at
      least in part due to the success of major pharmaceutical companies in producing a
      range of effective and safe anti-parasitic drugs. Research is needed because of
      the effects of parasites on animal welfare and the economic costs of parasites.
      However, there is little information on the actual costs of animal parasites.
      Another major reason for research is the development of drug resistance in
      protozoa, helminths and arthropods of veterinary importance. This is a serious
      problem particularly for sheep and goats in the southern hemisphere. A
      prioritised list of research requirements is suggested: (i) new drugs; (ii)
      resistance management; (iii) vaccines; (iv) breeding for resistance; (v) improved
      diagnostics; (vi) zoonoses; (vii) global warming and parasites. There is a major
      political challenge to raise the profile of veterinary parasitology and thus the
      funding essential for its advancement and the continued welfare and productivity
      of animals.

PMID- 11516578
TI  - The future of veterinary parasitology: a time for change?
AB  - The future of veterinary parasitology is discussed at a time when R&D funding
      from the pharmaceutical industry is declining, yet the opportunities for
      veterinary parasitologists to diversify their activities has never been greater.
      Emerging and re-emerging areas requiring input from veterinary parasitologists
      include: veterinary public health; conservation and wildlife diseases; emerging
      and exotic infectious diseases; surveillance strategies; economic effects of
      parasitic diseases; aquaculture; molecular epidemiology; dietary and biological
      control of parasitic diseases; animal welfare; organic agricultural systems;
      novel vaccination strategies; drug target characterisation and rational drug
      design. Without change, the survival of veterinary parasitology as a viable,
      distinct discipline is under threat. In this environment, veterinary
      parasitologists must be adaptable, imaginative and pro-active in terms of setting
      the agendas for establishing strategic alliances, promoting research needs and
      developing research programs.

PMID- 11516579
TI  - Role of the bovine immune system and genome in resistance to gastrointestinal
      nematodes.
AB  - Gastrointestinal nematode infections of cattle remain a constraint on the
      efficient raising of cattle on pasture throughout the world. Most of the common
      genera of parasites found in cattle stimulate an effective level of protective
      immunity in most animals within the herd after the animals have been on pasture
      for several months. In contrast, cattle remain susceptible to infection by
      Ostertagia for many months, and immunity that actually reduces the development of
      newly acquired larvae is usually not evident until the animals are more than 2
      years old. This prolonged susceptibility to reinfection is a major reason that
      this parasite remains the most economically important GI nematode in temperate
      regions of the world. Although, animals remain susceptible to reinfection for a
      prolonged period of time, there are a number of manifestations of the immune
      response that result in an enhanced level of herd immunity. These include a delay
      in the development time of the parasites, an increase in the number of larvae
      that undergo an inhibition in development, morphological changes in the worms,
      stunting of newly acquired worms, and most importantly a reduction in the number
      of eggs produced by the female worms. The overall result of these manifestations
      of immunity is a reduction in parasite transmission within the cattle herd. The
      immune mechanisms responsible for these different types of functional immunity
      remain to be defined. In general, GI nematode infections in mammals elicit very
      strong Th2-like responses characterized by high levels of Interleukin 4 (IL4),
      high levels of IgG1 and IgE antibodies, and large numbers of mast cells. In
      cattle, the most extensively studied GI nematode, in regards to host immune
      responses, is Ostertagia ostertagi. In Ostertagia infections, antigens are
      presented to the host in the draining lymph nodes very soon after infection, and
      within the first 3-4 days of infection these cells have left the nodes, entered
      the peripheral circulation, and have homed to tissues immediately surrounding the
      parasite where they become established. The immune response seen in the abomasum
      is in many ways are similar to that seen other mammalian hosts, with high levels
      of expression of IL4 in the draining lymph nodes and in lymphocytes isolated from
      the mucosa. But unlike a number of other systems, lymphocyte populations taken
      from Ostertagia infected cattle seem to be up-regulated for a number of other
      cytokines, most notably Interferon (IFN, implying that in Ostertagia infections,
      the immune response elicit is not simply a stereotypic Th2 response. In addition,
      effector cell populations in the tissues surrounding the parasites, are not
      typical, inferring the Ostertagia has evolved means to suppress or evade
      protective immune mechanisms. Studies have also demonstrated that the number of
      nematode eggs/gram (EPG) in feces of pastured cattle is strongly influenced by
      host genetics and that the heritability of this trait is approximately 0.30. In
      addition, EPG values are not "normally" distributed and a small percentage of a
      herd is responsible for the majority of parasite transmission. This suggests that
      genetic management of a small percentage of the herd can considerably reduce
      overall parasite transmission. A selective breeding program has been initiated to
      identify the host genes controlling resistance/susceptibility to the parasites.
      The best indicator of the number of Cooperia infecting a host is the EPG value,
      while Ostertagia is best measured by serum pepsinogen levels, weight gain, and
      measures of anemia. Other phenotypic measures are either not significantly
      associated with parasite numbers or are very weakly correlated. In addition,
      calves can be separated into three types: (1) Type I which never demonstrates
      high EPG values, (2) Type II which shows rises in EPG values through the first 2
      months on pasture which then fall and remain at levels associated with Type I
      calves, and (3) Type III calves which maintain high EPG levels. The approximate
      percentage of these calves is 25:50:25 respectively. Because these cattle are
      segregating for traits involved in resistance and susceptibility to GI nematodes,
      this resource population is being used to effectively detect the genomic
      locations of these Economic Trait Loci (ETL). For relational analysis between
      phenotype and genome location, over 80,000 genotypes have been generated by PCR
      amplification, and marker genotypes have been scored to produce inheritance data.
      The marker allele inheritance data is currently being statistically analyzed to
      detect patterns of co-segregation between allele haplotype and EPG phenotypes.
      Statistical power of this genome-wide scan has been strengthened by including
      genotypic data from the historic pedigree. In our herd, paternal half-sib
      families range from 5-13 progeny/sire, and extensive marker genotypes are
      available from ancestors of the population most of which are paternally descended
      from a single founding sire. Once ETL have been identified the next will be to
      refine ETL map resolution in attempt to discover the genes underlying disease
      phenotypes. Accurate identification of genes controlling resistance will offer
      the producer several alternatives for disease control. For a non-organic
      producer, the small percentage of susceptible animals can be targeted for drug
      administration. This approach would reduce both the cost of anthelmintics used
      and the odds for selection of drug resistant mutants, because the selective agent
      (drug) would not be applied over the entire parasite population. A second
      treatment option would be based on correcting a heritable immunologic condition.
      In this case, susceptible animals could be the targets for immunotherapy
      involving vaccines of immunomodulation. A final option would be genetic selection
      to remove susceptible animals from the herd. Producers with a high degree of risk
      for parasite-induced production losses, such as organic producers of producers in
      geographic areas with environmental conditions favorable to high rates of
      transmission would benefit the most from this strategy. In contrast, producers at
      low risk could take a more conservative approach and select against
      susceptibility when other factors were equal.

PMID- 11516580
TI  - Veterinary aspects of alveolar echinococcosis--a zoonosis of public health
      significance.
AB  - Human alveolar echinococcosis (AE), caused by the metacestode stage of
      Echinococcus multilocularis, is a serious zoonosis which caused up to 100%
      lethality in untreated patients before the 1970s, when modern methods of
      treatment were not yet established. AE occurs in large areas of the northern
      hemisphere mostly with low country-wide prevalences, but high prevalences of up
      to 4% have been reported from small population groups in highly endemic foci,
      e.g. from China. AE includes many veterinary aspects which are the topic of this
      review. Recent studies have shown that E. multilocularis has a wider geographic
      range than previously anticipated. There is evidence for growing populations of
      red foxes (Vulpes vulpes) in some areas, for increasing invasion of cities by
      foxes and also for establishment of the parasite cycle in urban areas. These and
      other factors may lead to an increased infection risk for humans. Significant
      progress has been made in the development of sensitive and specific new
      techniques for the intra vitam and post mortem diagnosis of intestinal E.
      multilocularis infection in definitive hosts, notably the detection of
      coproantigen by enzyme-linked immunosorbent assay and of copro-DNA by PCR. Both
      tests can also be used for the identification of E. multilocularis in faecal
      samples collected in the environment. Recommendations are given for chemotherapy
      and chemoprophylaxis of the intestinal infection in definitive hosts. In recent
      years, infections with the metacestode stage of E. multilocularis have not only
      been diagnosed in humans in several regions, including at least eight countries
      in central Europe, but also in animal species which do not play a role in the
      transmission cycle (wild and domestic pigs, dogs etc.). From 1987 to 2000 our
      group in Zurich has diagnosed 10 cases of AE in dogs and 15 in captive monkeys.
      In 2 dogs, concurrent infections of the intestine and of the liver with adult and
      larval stages of E. multilocularis, respectively, were observed for the first
      time. Clinical data are presented, and methods of diagnosis and treatment
      (surgery, chemotherapy) are described. Furthermore, small liver lesions caused by
      E. multilocularis were diagnosed in 10% of 90 slaughter pigs, and 2.9% of 522
      breeding sows had specific serum antibodies against parasite antigens. In view of
      the unpredictable epidemiological situation, all possible measures for preventing
      E. multilocularis infections in humans and in domestic animals should be
      initiated by the veterinary and health authorities.

PMID- 11516581
TI  - Managing parasiticide resistance.
AB  - Resistance to antiparasitic drugs is all too common in parasites of veterinary
      interest. The fact that resistance has arisen in so many different species of
      parasite and hosts against so many different drugs and in so many geographic
      areas suggests that the resistances may have common features. Such features may
      be useful in generating ideas for resistance management. Although describing the
      nature and presence of resistance remains an important objective, there is now a
      pressing need to develop improved methods of detection of resistance and to
      devise schemes for integrated parasite management (IPM). Multidisciplinary teams
      of researchers and extension workers are exploring new ways to deal with the
      problem of resistance.

PMID- 11516582
TI  - Forecasting habitat suitability for ticks and prevention of tick-borne diseases.
AB  - Climate and vegetation are the major factors affecting the distribution of ticks.
      Consequently, spatial distributions can be analysed by statistical methods that
      look for correlations between abiotic factors and known data about tick
      presence/absence. Remote sensing features can be obtained from a wide database of
      sensors with different characteristics, then applied to the problem of mapping
      prediction of tick distribution. Some studies had demonstrated that the use of
      these abiotic variables from satellite imagery has biological significance,
      therefore statistical accuracy of these distribution models can be interpreted
      under an ecological framework. Furthermore, models can be linked to these
      predictive maps, enabling the forecast of spatial and temporal dynamics of ticks,
      looking for seasonal patterns of activity and accurate use of acaricide
      treatments.

PMID- 11516583
TI  - New patterns of Trichinella infection.
AB  - Human and animal trichinellosis should be considered as both an emerging and
      reemerging disease. The reemergence of the domestic cycle has been due to an
      increased prevalence of Trichinella spiralis, which has been primarily related to
      a breakdown of government veterinary services and state farms (e.g., in countries
      of the former USSR, Bulgaria, Romania), economic problems and war (e.g., in
      countries of the former Yugoslavia), resulting in a sharp increase in the
      occurrence of this infection in swine herds in the 1990s, with a prevalence of up
      to 50% in villages in Byelorussia, Croatia, Latvia, Lithuania, Romania, Russia,
      Serbia, and the Ukraine, among other countries. The prevalence has also increased
      following an increase in the number of small farms (Argentina, China, Mexico,
      etc.) and due to the general belief that trichinellosis was a problem only until
      the 1960s. The sylvatic cycle has been studied in depth at both the
      epidemiological and biological level, showing the existence of different
      etiological agents (Trichinella nativa, Trichinella britovi, Trichinella
      murrelli, Trichinella nelsoni) in different regions and the existence of "new"
      transmission patterns. Furthermore, the role of game animals as a source of
      infection for humans has greatly increased both in developed and developing
      countries (Bulgaria, Canada, Lithuania, some EU countries, Russia, USA, etc.).
      The new emerging patterns are related to non-encapsulated species of Trichinella
      (Trichinella pseudospiralis, Trichinella papuae, Trichinella sp.), infecting a
      wide spectrum of hosts (humans, mammals including marsupials, birds and
      crocodiles) and to encapsulated species (T. spiralis, T. britovi, and T.
      murrelli) infecting herbivores (mainly horses). The existence of non-encapsulated
      species infecting mammals, birds and crocodiles had probably remained unknown
      because of the difficulties in detecting larvae in muscle tissues and for the
      lack of knowledge on the role of birds and crocodiles as a reservoir of
      Trichinella. On the other hand, it is not known whether horse and crocodile
      infections existed in the past, and their occurrence has been related to improper
      human behavior in breeding. The problem of horse-meat trichinellosis is
      restricted to France and Italy, the only two countries where horse-meat is eaten
      raw, whereas mutton and beef have been found to be infected with Trichinella sp.
      only in China.

PMID- 11516584
TI  - Parasite vaccines--a reality?
AB  - Over the last decade, the anti-parasitics market has been the fastest growing
      sector of the overall $18 billion animal health market. While drugs for the
      treatment of parasites of livestock still dominate this sector and will continue
      to be developed or re-formulated, because of consumer demands for chemical-free
      food and of concerns regarding the environment and animal welfare there is a
      growing interest in the development of safe and effective vaccines. There is also
      a call for vaccines in the lucrative $3 billion-plus companion animal market.
      These demands for vaccines will add a greater impetus to an area that has seen
      tremendous success in the last 15 years. A number of anti-parasite vaccines have
      been developed, e.g. the recombinant 45w and EG95 oncosphere proteins against
      Taenia ovis and Echinococcus granulosis, respectively, and the Bm86 vaccine
      against Boophilus microplus. In addition, the cathepsin L vaccines against the
      liver fluke, Fasciola hepatica, and the H11 vaccine against Haemonchus contortus
      are progressing well. There are also many additional vaccine candidates for H.
      contortus and for other nematodes such as Ostertagia and Trichostrongylus spp.
      that may ultimately lead to broad-spectrum gastrointestinal worm vaccines. Live
      or attenuated-live vaccines are available for the control of avian coccidiosis,
      toxplasmosis in sheep and anaplasmosis in cattle, although molecular vaccines
      against protozoans are still proving elusive. The wealth of information in
      genomics, proteomics and immunology that has been forthcoming together will new
      methods of vaccine production and delivery should see many new vaccines reach the
      marketplace in the near future.

PMID- 11516585
TI  - The role of molecular biology in veterinary parasitology.
AB  - The tools of molecular biology are increasingly relevant to veterinary
      parasitology. The sequencing of the complete genomes of Caenorhabditis elegans
      and other helminths and protozoa is allowing great advances in studying the
      biology, and improving diagnosis and control of parasites. Unique DNA sequences
      provide very high levels of specificity for the diagnosis and identification of
      parasite species and strains, and PCR allows extremely high levels of
      sensitivity. New techniques, such as the use of uniquely designed molecular
      beacons and DNA microarrays will eventually allow rapid screening for specific
      parasite genotypes and assist in diagnostic and epidemiological studies of
      veterinary parasites. The ability to use genome data to clone and sequence genes
      which when expressed will provide antigens for vaccine screening and receptors
      and enzymes for mechanism-based chemotherapy screening will increase our options
      for parasite control. In addition, DNA vaccines can have desirable
      characteristics, such as sustained stimulation of the host immune system compared
      with protein based vaccines. One of the greatest threats to parasite control has
      been the development of drug resistance in parasites. Our knowledge of the basis
      of drug resistance and our ability to monitor its development with highly
      sensitive and specific DNA-based assays for 'resistance'-alleles will help
      maintain the effectiveness of existing antiparasitic drugs and provide hope that
      we can maintain control of parasitic disease outbreaks.

PMID- 11516586
TI  - Treatment vs non-treatment of helminth infections in cattle: defining the
      threshold.
AB  - Helminth infections are an important cause of lost productivity in livestock
      world-wide, often necessitating anthelmintic treatment. However, a large part of
      the anthelmintics are used indiscriminately because the parasite levels are too
      low to justify treatment or because the treatments are not correctly programmed,
      resulting in undertreatment or overtreatment. The objective of this paper is to
      discuss possible thresholds for anthelmintic treatment of some of the more
      important helminth infections in livestock, i.e. gastrointestinal nematodes,
      lungworms and liver fluke, to promote a more appropriate use of anthelmintics.
      When possible, a distinction is made between therapeutic thresholds, production
      based thresholds and preventive thresholds. A "therapeutic threshold" is intended
      to identify (an) animal(s) with parasite levels that necessitate immediate
      treatment. The therapeutic threshold is basically the diagnosis of clinical
      disease, and can be determined relatively easily for the parasites discussed in
      this paper. A "production-based threshold" is intended to measure the effects of
      sub-clinical parasitism on productivity parameters, such as weight gain and milk
      yield, before clinical disease occurs. Finally, a "preventive threshold" is meant
      to predict future infection levels, to enable the application of appropriate
      control measures.

PMID- 11516587
TI  - Wolbachia in filarial nematodes: evolutionary aspects and implications for the
      pathogenesis and treatment of filarial diseases.
AB  - The presence of intracellular bacteria in the body of various species of filarial
      nematodes, including important parasites such as Brugia malayi, Dirofilaria
      immitis, and Onchocerca volvulus, was observed as early as the mid-1970s. These
      bacteria were shown to be transovarially transmitted (from the female worm to the
      offspring) and to be present in significant amounts in the body of the nematode.
      As highlighted by their discoverers, the potential importance of these bacteria
      is fairly obvious: (1) bacteria-derived molecules should be considered as having
      an immunological and pathological role in filarial diseases; (2) the interaction
      between the bacteria and the filarial host deserves investigation, in view of the
      possibility that the bacteria are needed by the host nematode and could thus
      represent a target for therapy. Other authors, independently from the discovery
      of these intracellular bacteria, showed that the antibiotic tetracycline (which
      is well known for its efficacy on intracellular bacteria) had detrimental effects
      on two species of filarial nematodes (Brugia pahangi and Litomosoides
      sigmodontis). It is therefore surprising that for more than 20 years, no further
      investigations focused on the bacteria of filarial nematodes, nor on the anti
      filarial properties of tetracycline. Recently, the bacteria of filarial nematodes
      have been independently "rediscovered" by research groups from the schools of
      Hamburg, Liverpool and Milan. These bacteria are now classified as Wolbachia, and
      the basic aspects of their phylogenetic history and relationship with the
      Wolbachia of arthropods have been reconstructed. In addition, their implications
      for the pathogenesis and treatment of filarial diseases have started to be
      uncovered. This paper, which is authored by representatives of the three European
      schools who reopened this research area, reviews our present knowledge of these
      fascinating microorganisms, highlighting the complexity of a symbiotic system
      which involves, in addition to the nematode and its bacterium, the vertebrate
      host.

PMID- 11516588
TI  - A psychometric evaluation of the BDI-II in treatment-seeking substance abusers.
AB  - The Beck Depression Inventory-II (BDI-II) was administered to 416 consecutive
      male admissions to a 28-day residential chemical dependence treatment program as
      part of a routine intake procedure. Psychometric analyses revealed that the BDI
      II scores were internally consistent in this treatment-seeking population based
      on coefficient alpha. The mean BDI-II score for patients in this study was higher
      than that noted for other clinical samples in previous studies. The use of the
      BDI-II for clinical decision making with chemically dependent individuals is
      discussed in light of this elevated distribution of scores. Confirmatory factor
      analytic examinations of the instrument revealed that a three-factor model, with
      cognitive, affective, and somatic symptoms loading as separate factors, provided
      the most adequate account of the data. In total, the study supported the use of
      the BDI-II for the assessment of depression in chemically dependent male patients
      entering a residential treatment program at a VAMC facility, provided population
      specific normative data is utilized for making clinical decisions.

PMID- 11516589
TI  - Outcomes of a comprehensive treatment program for adolescents with a substance
      use disorder.
AB  - Outcomes of a multimodal residential treatment program for adolescents were
      compared with usual care. The quasiexperimental design included pretest, 3-month
      posttest, and 6-month follow-up of program referrals (mean age 16; 53% male). The
      intervention group (IG) comprised referrals who entered the program (n=61) and
      the comparison group (CG) comprised referrals who did not enter the program
      (n=60). The six outcomes (substance use, criminal behavior, social functioning,
      psychological distress, physical health, and HIV risk-taking behavior) were
      assessed using the Opiate Treatment Index and the Symptom Checklist-90-Revised.
      The study groups demonstrated equivalent improvement on all six outcomes.
      Multiple factors are likely to have influenced these results, including
      inadequate program implementation and differential drop-out. There was, however,
      a higher prevalence of multiple improvements among the IG than the CG. It is
      concluded that adolescents with a PSUD can improve, however, a superior means of
      achieving this improvement has yet to be demonstrated.

PMID- 11516590
TI  - Gender differences in income after substance abuse treatment.
AB  - This study asked whether men and women who enrolled in substance use treatment
      reported similar changes in income from work, public assistance, and crime over
      time. Income data were analyzed for 261 substance users (77 women, 184 men) who
      entered day or residential treatment, and completed Addiction Severity Index
      measures at treatment entry and up to 18 months later. Over time, respondents
      reported increases in employment income. People whose main source of income at
      baseline had been crime or public assistance showed significant decreases
      respectively in income from crime or public assistance. Men made greater gains in
      work income than women did. Across time, men were more likely to be employed than
      women were. Findings show the economic value of substance use treatment, but less
      improvement in employment outcomes for women than men.

PMID- 11516591
TI  - Implementation of a clinic policy of client-regulated methadone dosing.
AB  - A six-month interval (baseline) during which methadone doses above 99 mg required
      individual approval by the clinic's physician was compared with the subsequent 16
      month period in which a policy of patient-regulated methadone dosing with no
      preset upper limit was implemented. During the later phase, all patients were
      required to remain at each selected dose for a minimum of four days, and standard
      compliance-based take-home dosing procedures were followed. For patients in the
      study sample (n=57), the daily maximum methadone dose increased from 165 mg
      during baseline to 300 mg during the self-regulation period, while their average
      daily methadone dose increased from 76.84 mg to 80.04 mg (W=473, n=57, p=0.01).
      Monthly percent of opiate-positive urine specimens decreased significantly from
      5.26% during baseline to 1.64% during the self-regulated dose period (W=169,
      n=57, p<0.01), and use of other drugs remained unchanged. No patient failed to
      show possession of recalled take-home doses, and no instances of liquid methadone
      diversion were reported by law enforcement agencies in the area.

PMID- 11516593
TI  - Concurrent versus delayed smoking cessation treatment for persons in early
      alcohol recovery. A pilot study.
AB  - This pilot study investigated the efficacy of initiating a smoking cessation
      intervention early in inpatient treatment for alcohol dependence versus shortly
      after an inpatient stay. Thirty-six male smokers recruited from an inpatient
      substance abuse treatment program were randomly assigned to begin smoking
      cessation either two weeks (concurrent treatment) or six weeks (delayed
      treatment) after admission to the substance abuse program. Smoking cessation
      treatment involved three sessions of individual smoking cessation treatment plus
      eight weeks of transdermal nicotine replacement. Significantly fewer participants
      began the delayed treatment than the concurrent treatment. Few participants were
      smoking-abstinent at follow-up, and the timing of treatment onset did not have an
      impact on smoking outcome. Clinical trials with larger samples may be needed to
      better evaluate the efficacy of concurrent versus delayed treatment and to test
      the efficacy of more aggressive interventions with smokers in early alcohol
      recovery.

PMID- 11516594
TI  - Suggested specifications for a standardized Addiction Severity Index database.
AB  - The Addiction Severity Index (ASI) has become one of the most widely used
      instruments in the addictions field. As a result of its wide popularity, there
      are multiple versions of the instrument in use, and a wide range of computer
      systems used to collect and/or store ASI data. Thus, it has been difficult for
      different users and systems to share ASI data. This difficulty significantly
      reduces the value of the information for treatment providers, policy makers, and
      researchers. This article provides operational definitions and specifications for
      a "Standard ASI Database." Descriptions for standard variable names, data types,
      field lengths, value labels, range checks, and programming notes for all items in
      the fifth edition of the ASI are available electronically from the senior.
      Examples from the full protocol and the rationale for producing the Standard ASI
      Database elements are illustrated here. It is hoped that the format suggested
      will become the "industry standard" for ASI data storage among all users of the
      ASI and that, regardless of the software used or the method of data collection,
      there will be a single, standard format for all ASI databases. The potential
      applications from such a database would benefit treatment providers/clinicians
      and researchers as well as payers and policy makers.

PMID- 11516595
TI  - Exploring the self-reported sexual problems and concerns of drug-dependent males
      and females in modified, therapeutic community treatment.
AB  - The importance of sexual trauma and sexual problems in the treatment of
      chemically dependent persons has long been recognized by clinicians working with
      this population. This study was undertaken to describe the degree of self
      reported sexual problems and concerns for 163 males admitted into a Philadelphia-
      or New York City-based modified therapeutic community (TC) program and 100
      females admitted to the same New York City program. Results indicated that the
      majority of men and women identified some sexual problems and concerns shortly
      after being admitted, with females in the New York City sample endorsing sexual
      problems more often than males in the Philadelphia or New York City samples.
      These findings are considered in view of the fact that these clients' sexual
      problems were usually not addressed on their Master Treatment Plans. The
      implications of addressing or not addressing these sexual problems are
      considered.

PMID- 11516596
TI  - Characteristics of terminal cancer patients who committed suicide during a home
      palliative care program.
AB  - Cancer patients may commit suicide at any stage of the disease and many risk
      factors of suicide have been described in the literature. To identify the
      possible vulnerability factors of suicide in five terminal cancer patients who
      committed suicide while they were cared for at home by well-trained palliative
      care teams, a psychological autopsy study was carried out by reviewing their
      medical records; their report of symptoms at the time of care; and with the
      caregivers', doctors', and nurses' recollection of events by means of a
      structured interview prepared ad hoc. We collected data regarding the physical,
      emotional, and social suffering of the patients, their personality profile, and
      their feelings with respect to the illness and disability. The interviews lasted
      for a mean of two hours and were performed from 2-8 years after the suicide
      events by the social worker at the Rehabilitation and Palliative Care Division.
      The interviews took place between June 1996 and January 1998. All the patients
      showed great concern about the lack of autonomy and independence, refused
      dependence on others and had fear/worry of losing their autonomy. Four patients
      presented functional and physical impairments, uncontrolled pain, awareness of
      being in the terminal stage, and mild to moderate depression. They had a feeling
      of hopelessness consequent to their clinical conditions, fear of suffering, and
      feeling of being a burden on others. They had a strong character and managerial
      professions. They had isolated themselves from others and they had previously
      talked about suicide. Before committing suicide, three patients had adverse
      physical/emotional consequences to the oncological treatments-they showed
      aggressiveness towards their family and one towards the home care physician.
      Multiple vulnerability factors were present simultaneously in all patients.
      However, the loss of, and the fear of losing, autonomy and their independence and
      of being a burden on others were the most relevant. The identification of a
      cancer patient at risk of committing suicide forms the first step for the
      prevention of and the setting up of adequate psychosocial rehabilitation of these
      patients whenever possible.

PMID- 11516597
TI  - Fatigue in ambulatory patients with advanced lung cancer: prevalence, correlated
      factors, and screening.
AB  - Although it has been indicated that patients with lung cancer experience higher
      level of fatigue than patients with other cancers, few published studies have
      focused on the characteristics of this fatigue and how it interferes with daily
      activities. The purpose of this study was to clarify fatigue prevalence and the
      factors correlated with fatigue, and to develop a screening method for fatigue in
      patients with advanced lung cancer. One hundred fifty-seven patients completed
      two fatigue scales (Cancer Fatigue Scale [CFS], and Fatigue Numerical Scale
      [FNS]) plus other measures, along with a self-administered questionnaire asking
      whether fatigue had interfered with any of 7 areas of daily activities. Fifty
      nine percent of patients had experienced clinical fatigue, which was defined as
      fatigue that interfered with any daily activities. Logistic regression analysis
      demonstrated that symptoms of dyspnea on walking, appetite loss, and depression
      were significant correlated factors. Both CFS and FNS were found to have
      sufficient sensitivity and specificity for use as a screening tool. The results
      indicated that fatigue is a frequent and important symptom, which is associated
      with both physical and psychological distress in this population. The CFS and FNS
      were confirmed to have sufficient screening ability.

PMID- 11516598
TI  - Family reports of dying patients' distress: the adaptation of a research tool to
      assess global symptom distress in the last week of life.
AB  - Understanding dying patients' symptom distress is an important component of
      efforts to improve care at the end of life. It can, however, be problematic to
      conduct research with dying patients. Family members can serve as sources of
      information about decedents' last days of life. In order to assess family reports
      of decedents' global symptom distress in the last week of life, we adapted the
      Memorial Symptom Assessment Scale Global Distress Index (MSAS-GDI), a brief
      measure of patient global symptom distress, for use in a retrospective study of
      family reports about end-of-life care. It was administered to a sample of 103
      family members to assess the psychometric properties of the instrument in
      bereaved family members. The Family MSAS-GDI consists of questions about 11
      psychological and physical symptoms commonly experienced by dying patients. The
      majority of family members were able to respond to the scale items. The mean
      Family MSAS-GDI score was 1.14 (SD = 0.87) with a range of 0 to 3.73. The scale
      demonstrated good internal consistency (alpha = 0.82). The average item-total
      correlation was r = 0.49 and the average inter-item correlation was r= 0.30,
      suggesting items were moderately correlated with the overall total scale and with
      each other. The Family MSAS-GDI could prove to be a useful tool in assessing and
      tracking global symptom distress in dying patients.

PMID- 11516599
TI  - Long-term safety of oral transmucosal fentanyl citrate for breakthrough cancer
      pain.
AB  - This open-label study evaluated the long-term safety and tolerability of oral
      transmucosal fentanyl citrate (OTFC) in ambulatory cancer patients with
      breakthrough pain undergoing cancer care at 32 university- or community-based
      practices. Patients had participated in a previous short-term titration trial of
      OTFC, were experiencing at least one episode per day of breakthrough pain, and
      had achieved relief of their breakthrough pain with an opioid. Patients received
      OTFC units at a starting dosage strength determined in the short-term trial (200
      1600 microg). Outcome measures included number of successfully treated
      breakthrough pains, global satisfaction rating (0 = poor through 4 = excellent),
      and side effects. In total, 41,766 units of OTFC were used to treat 38,595
      episodes of breakthrough pain in 155 patients. Number of treatment days ranged
      from 1 to 423 (mean, 91 days). Patients averaged 2.9 breakthrough pain episodes
      per day. About 92% of episodes were successfully treated with OTFC and there was
      no trend toward decreased effectiveness over time. Most patients (61%) did not
      require dose escalation during treatment. Global satisfaction ratings were
      consistently above 3, indicating very good to excellent relief. Common adverse
      events associated with OTFC were somnolence (9%), constipation (8%), nausea (8%),
      dizziness (8%), and vomiting (5%). Six patients (4%) discontinued therapy due to
      an OTFC-related adverse event. There were no reports of abuse and no concerns
      about the safety of the drug raised by patients or families. OTFC was used safely
      and effectively during long-term treatment of breakthrough pain in cancer
      patients at home.

PMID- 11516600
TI  - Panel-based pain management in primary care. a pilot study.
AB  - Although pain is an extremely common symptom presenting to primary care
      physicians, it frequently is not optimally managed. The purpose of this
      feasibility study was to develop and pilot-test an efficient, rapid assessment
      and management approach for pain in busy community practices. The intervention
      utilized the Dartmouth COOP Clinical Improvement System (DCCIS) and a telephone
      based, nurse-educator intervention. Patients from four primary care practices in
      rural New Hampshire and Vermont were screened by mail for the presence of
      persistent pain. Patients with mild to severe pain were randomized to either the
      usual care control group (n = 383) or the intervention group (n = 320). Patients
      who reported pain but no psychosocial problems received a summary of identified
      problems and targeted educational material via mail (DCCIS). Patients who
      reported pain and psychosocial problems received the DCCIS intervention and calls
      from a nurse-educator who provided pain self-management strategies and a problem
      solving approach for psychosocial problems. Post-treatment evaluation revealed
      that patients in the intervention group scored significantly better on the Pain,
      Physical, Emotional, and Social subscales of the SF-36 and on the total score of
      the Functional Interference Scale, as compared to a usual care control group.
      Feasibility and acceptability of the approach were demonstrated; however, the
      conclusions based on analyses of the post-treatment outcomes were tempered by
      baseline imbalances across groups.

PMID- 11516601
TI  - The Child-Adult Medical Procedure Interaction Scale-Short Form (CAMPIS-SF):
      validation of a rating scale for children's and adults' behaviors during painful
      medical procedures.
AB  - This study evaluated the concurrent and construct validity of the Child-Adult
      Medical Procedure Interaction Scale-Short Form (CAMPIS-SF), a behavior rating
      scale of children's acute procedural distress and coping, and the coping
      promoting behaviors and distress promoting behaviors of their parents and the
      medical personnel who were present in the medical treatment room. Sixty preschool
      children undergoing immunizations at a county health department served as
      subjects. Videotapes of the procedures were scored using three observational
      measures in addition to the CAMPIS-SF. Also, parent, nurse, and child report
      measures of child distress, fear, pain, and cooperation were obtained. Results
      indicated that the validity of the CAMPIS-SF codes of Child Coping, Child
      Distress, Parent Coping Promoting, Parent Distress Promoting, Nurse Coping
      Promoting, and Nurse Distress Promoting behaviors was supported by multiple
      significant correlations with the other measures. The interrater reliability of
      the 5-point CAMPIS-SF scales was good to excellent. The results emphasize that
      the CAMPIS-SF scales can be used to monitor not only children's acute procedural
      distress, but also their coping and the various adults' behaviors that
      significantly influence children's distress. Further, because of the CAMPIS-SF's
      ease of use, it is likely that the study of the effects of the social environment
      on children's distress and coping will be facilitated.

PMID- 11516602
TI  - The association between physiological and behavioral pain measures in 0- to 3
      year-old infants after major surgery.
AB  - To estimate the association between behavioral and physiological pain measures
      and to identify determinants predicting the level of association, the COMFORT
      'behavior' scale, heart rate (HR), mean arterial pressure (MAP), and the
      variability of HR and MAP (HRV and MAPV) were assessed every 3 hours after major
      abdominal or thoracic surgery. Subjects were 204 infants aged 0-3 years. The
      within-subject correlations, using the repeated measures, were 0.37, 0.44, 0.48,
      and 0.49 for COMFORT 'behavior' with HRV, HR, MAP, and MAPV, respectively.
      Neonates had lower behavior-physiology correlations than the older infants, due
      to low pain scores. Pain characteristics significantly predicted the COMFORT
      'behavior'-HR/MAP correlations, suggesting that the behavior-physiology
      correlations increase with increasing pain. The behavior-physiology correlations
      were not greatly affected by physical condition. These data demonstrate large
      interindividual differences in behavior-physiology correlations after major
      surgery in 0- to 3-year-old infants. These differences should be further explored
      in future research.

PMID- 11516603
TI  - Video-assisted thoracoscopic sympathectomy-splanchnicectomy for pancreatic cancer
      pain.
AB  - Patients with unresectable pancreatic cancer often suffer severe pain. Various
      techniques are available for pain control. We present a patient with pancreatic
      cancer who underwent unilateral video-assisted thoracoscopic sympathectomy
      splanchnicectomy and had complete pain relief. This minimally invasive procedure
      offers promise in carefully selected patients with severe pain from pancreatic
      cancer and other conditions which are not amenable to conventional interventions.

PMID- 11516604
TI  - A case of difficult pain in a patient with chronic renal failure and
      calciphylaxis.
AB  - A difficult pain occurred in a man with chronic renal failure as a result of the
      underlying condition of calciphylaxis. In this condition, calcification of small
      and medium-sized arteries occurs, which may result in ischemia and gangrene. In
      general, the prognosis is poor, with mortality rates ranging from 23-63%. Pain
      associated with this condition has been previously reported. In this report, the
      pain occurred in the lower limbs and penis, and was associated with local
      necrosis. The pain was observed to be significantly worse on dialysis. A
      multiprofessional approach to care ultimately resulted in good symptom control.

PMID- 11516605
TI  - Gabapentin for pain control in cancer patients' wound dressing care.
AB  - A patient with mycosis fungoides illustrates the problem of pain management
      during wound care and suggests the utility of a novel treatment, gabapentin. Skin
      lesions, be they induced through necrosis of tumor, therapy (e.g., radiotherapy),
      or by pressure ulceration, are often the cause of continuous pain or acute wound
      dressing pain. Optimizing the analgesic treatment in those patients is thus of
      major importance. Anti-inflammatory drugs and opioids are the cornerstones in the
      treatment of cancer pain but are rarely sufficient to control wound pain.
      Different adjuvant techniques can be used, including topical analgesics,
      psychological distraction techniques, anxiolytics, and co-analgesics. There is
      growing evidence that anticonvulsants, and sodium channel blockers in particular,
      are effective not only in neuropathic but also in inflammatory pain. Gabapentin,
      a voltage sensitive sodium and calcium channel blocker, was used as a co
      analgesic to supplement morphine in this case of cancer wound dressing pain.

PMID- 11516606
TI  - Developmental dyscalculia.
AB  - Developmental dyscalculia is a specific learning disability affecting the
      acquisition of arithmetic skills in an otherwise-normal child. Although poor
      teaching, environmental deprivation, and low intelligence have been implicated in
      the etiology of developmental dyscalculia, current data indicate that this
      learning disability is a brain-based disorder with a familial-genetic
      predisposition. The neurologic substrate of developmental dyscalculia is thought
      to involve both hemispheres, particularly the left parietotemporal areas.
      Developmental dyscalculia is a common cognitive handicap; its prevalence in the
      school population is about 5-6%, a frequency similar to those of developmental
      dyslexia and attention-deficit-hyperactivity disorder. Unlike these, however, it
      is as common in females as in males. Developmental dyscalculia frequently is
      encountered in neurologic disorders, examples of which include attention-deficit
      hyperactivity disorder, developmental language disorder, epilepsy, and fragile X
      syndrome. The long-term prognosis of developmental dyscalculia is unknown; it
      appears, however, to persist, at least for the short-term, in about half of
      affected preteen children. The consequences of developmental dyscalculia and its
      impact on education, employment, and psychologic well-being of affected
      individuals are unknown.

PMID- 11516607
TI  - Extraoperative cortical stimulation of motor function in children.
AB  - The purpose of the study was to investigate factors altering the amperage
      threshold needed to provoke functional responses in children with epilepsy.
      Twenty patients (4-18 years of age) who underwent epilepsy surgery at our
      institution from 1996-2000 after insertion of subdural grid electrodes were
      reviewed retrospectively. Extraoperative electrical cortical stimulation was
      performed with 50-Hz biphasic pulses of 0.2 ms in duration using a "distance
      reference" technique. Amperage thresholds of primary motor responses and
      afterdischarges were evaluated. The patients were grouped according to underlying
      pathology: eight with neuronal migration disorders (group A) and 12 with other
      disorders (group B). The motor cortex was defined successfully in all children
      because the afterdischarges threshold was higher than the motor cortical
      threshold. Amperage thresholds ranged from 2-20 mA (mean = 7.7) for primary motor
      function. An inverse relationship was found between amperage threshold and age:
      the younger the patient, the higher the threshold (P = 0.0005). Patients in group
      A required a higher amperage (2-20 mA, mean = 8.6) for motor cortical mapping
      than those in group B (2-14 mA, mean = 6.4). Younger children with neuronal
      migration disorders require a higher amperage threshold to achieve adequate motor
      functional mapping with careful observation of afterdischarges.

PMID- 11516608
TI  - Safety, tolerability, and pharmacokinetics of remacemide in children.
AB  - Eleven patients (nine males, two females), 9-14 years of age, received adjunctive
      therapy with remacemide in an open ascending-dose study at two residential
      centers in the United Kingdom. Children taking enzyme-inducing drugs were given
      remacemide twice daily, starting at approximately 4 mg/kg per day and doubling
      the dose at two weekly intervals to a target dose of approximately 16 mg/kg per
      day. Children not taking enzyme-inducing drugs (n = 5) received half of these
      doses. After the dose-escalation phase, remacemide was slowly withdrawn over 2
      weeks except in two children who, because of apparent benefit, entered a
      continuation phase. Remacemide generally was well tolerated in doses up to 13.5
      mg/kg per day. Adverse events were similar to those reported in adults, with
      central nervous system and gastrointestinal events being the most common. One
      patient died after a suspected seizure, which was unlikely to have been related
      to remacemide treatment. No adverse effects on neuropsychologic functioning were
      observed; effects on vital signs and laboratory variables were not clinically
      significant. The pharmacokinetic profile for remacemide and its desglycinyl
      metabolite in children is similar to that seen in adult patients. Plasma
      concentrations of remacemide and the desglycinyl metabolite are reduced in the
      presence of concomitant antiepileptic drugs with hepatic enzyme-inducing
      activity.

PMID- 11516609
TI  - Expression of calbindin and calretinin in the human ganglionic eminence.
AB  - The conspicuous ganglionic eminence representing a part of the telencephalic
      proliferative zone contains neuroblasts of the striatum. Recently it has been
      found to contribute significantly to the class of interneurons in the cerebral
      cortex. Subpopulations of cortical interneurons contain calretinin and calbindin.
      The expression of calretinin and calbindin in the ganglionic eminence and
      adjacent areas has been investigated immunocytochemically during fetal
      development using the brains of 10 infants ranging in age from 16 and 26 weeks
      gestation. Between 16 and 20 weeks gestation, numerous calretinin-immunreactive
      nerve cells are found in the ganglionic eminence, particularly in the mantle and
      the intermediate zones. The number of calretinin-immunoreactive cells decreases
      gradually from 21 weeks gestation onwards. Larger calbindin-immunoreactive cells
      are seen in the ganglionic eminence, and their number increases from 20 weeks
      gestation in the mantle zone. These results may indicate that calretinin
      immunoreactive precursor cells, found in the ganglionic eminence, tangentially
      migrate toward the cortex. Moreover, the mantle zone displaying a specific
      calretinin and calbindin immunolabeling may represent an intermediate target for
      outgrowing axons. The findings are discussed with regard to central nervous
      system complications in preterm infants involving the ganglionic eminence.

PMID- 11516610
TI  - Clinical spectrum of reversible posterior leukoencephalopathy syndrome.
AB  - Reversible posterior leukoencephalopathy syndrome is a recently recognized
      disorder with characteristic radiologic findings that mainly involve the
      white/gray matter of the parieto-occipital lobes. This complex syndrome is
      associated with cyclosporine A therapy or a variety of other conditions in which
      blood pressure rises acutely. Twelve patients from a variety of conditions who
      met the diagnostic criteria for this syndrome were studied. Interestingly, three
      of these patients had intra-abdominal neurogenic tumors, which have rarely been
      reported. Initial cranial magnetic resonance imaging scans revealed fairly
      symmetric areas of increased T(2) signal involving both white and gray matter of
      parieto-occipital lobes in the majority of the patients. However, the lesions
      were often located outside the parieto-occipital regions. Four patients had
      occipital region magnetic resonance spectroscopy during the acute phase, which
      revealed high lactate peak and normal N-acetyl aspartate/creatine and choline
      peaks. With appropriate treatment, most patients recovered from this syndrome and
      experienced almost complete resolution of brain lesions on follow-up magnetic
      resonance imaging. One patient, however, continued to have small residual
      hemosiderin deposits on a follow-up magnetic resonance imaging with neurologic
      sequellae. In conclusion, a better understanding of this complex syndrome may
      obviate unnecessary investigations and allow management of the associated
      problems in prompt and appropriate ways.

PMID- 11516611
TI  - Oral motor dysfunction and feeding difficulties in nephropathic cystinosis.
AB  - Nephropathic cystinosis is a genetic disorder in which the amino acid cystine
      accumulates in lysosomes, resulting in multiorgan dysfunction. Progressive
      neuromuscular dysfunction, with bulbar and upper extremity weakness, has been
      described in adults with this disorder. The purpose of the present study was to
      determine whether there was evidence of early bulbar involvement, suggested by
      feeding difficulties or oral motor dysfunction in these patients, and whether the
      feeding and oral motor problems were associated with other evidence of neurologic
      dysfunction. Twenty-two children and adolescents with nephropathic cystinosis
      were studied. Parents completed questionnaires on feeding history and oral motor
      problems. Eighteen patients were given an oral motor examination, and 14 received
      a complete neurologic examination. The majority of children had a history of
      feeding difficulties. Seven children required a gastrostomy tube. Abnormalities
      on oral motor examination included hypotonia, abnormal gag reflex, and throaty or
      congested voice. Abnormalities on neurologic examination included hypotonia,
      muscle weakness, gross and fine motor dysfunction, and ataxia. The results
      indicate that feeding difficulties and oral motor dysfunction are common in
      children with cystinosis and appear to correlate with the general degree of
      neurologic dysfunction. Long-term follow-up is necessary to determine whether the
      early oral motor problems predict the later development of the progressive
      myopathy observed in adults with cystinosis.

PMID- 11516612
TI  - Acute onset of infantile spinal muscular atrophy.
AB  - Two patients with acute generalized weakness and areflexia are presented. The
      electrophysiologic studies in both revealed evidence of decreased conduction
      velocity and mixed axonal and demyelinating neuropathy, suggestive of the
      diagnosis of Guillain-Barre syndrome. The young ages of the patients and their
      failure to respond to immunoglobulin therapy were the major clues to the final
      diagnosis of spinal muscular atrophy type I. Blood for DNA study revealed
      homozygous deletion mutation in exons 7 and 8 of the survival motor neuron gene.
      This diagnosis should be considered in every child under 1 year of age who
      presents with acute weakness because Guillain-Barre syndrome in this age group is
      rare.

PMID- 11516613
TI  - Fukuyama muscular dystrophy associated with lack of C-terminal domain of
      dystrophin.
AB  - The first reported female patient with the Fukuyama type of congenital muscular
      dystrophy associated with a lack of C-terminal domain of dystrophin is presented.
      Clinically, the patient had characteristic features and magnetic resonance
      imaging findings of Fukuyama muscular dystrophy. Dystrophin analysis revealed a
      lack of the C-terminal domain but preserved N-terminal and rod domains of
      dystrophin in biopsied muscle. Moreover, she had reduced expression of merosin,
      syntrophin, and beta-dystroglycan in the skeletal muscle. Reverse transcriptase
      polymerase chain reaction analysis of mRNA in the patient's muscle illustrated a
      complete lack of exons 71-74 of the dystrophin gene. These deletions, which
      remove the beta-dystroglycan and syntrophin binding site, may cause changes in
      the function of both beta-dystroglycan and syntrophin in human muscle.

PMID- 11516615
TI  - Transverse myelopathy: an initial presentation of acute leukemia.
AB  - An 8-year-old female with a history of back pain and loss of the ability to walk
      is presented. Transverse myelopathy was considered clinically after assessing
      magnetic resonance imaging results of the thoracic spine. Acute lymphoblastic
      leukemia was diagnosed approximately 5 months after the beginning of symptoms.
      Reviewing the related literature suggests that transverse myelopathy is not
      uncommon in neoplastic diseases. Children with a disorder of the spinal cord,
      especially if accompanied with fatigue and anemia, might have transverse
      myelopathy-associated malignant disease. Transverse myelopathy can be the initial
      presentation of acute lymphoblastic leukemia.

PMID- 11516614
TI  - The protective effect of brachial plexus palsy in purpura fulminans.
AB  - Acute infectious purpura fulminans is reported in a 16-month-old male with a
      history of posttraumatic asplenia and complete left brachial plexus palsy. This
      patient developed peripheral necrosis of both lower extremities and the right
      upper extremity, whereas the left upper extremity was completely spared from
      ischemia and tissue damage. Amputation of four digits on the right hand and
      debridement of both lower extremities were required. This patient demonstrated
      the protective effect of a traumatic sympathectomy, which suggests the
      requirement of an intact sympathetic reflex in the development of purpura
      fulminans.

PMID- 11516616
TI  - Recurrent hypoglycemic hemiparesis and aphasia in an adolescent patient.
AB  - A 12-year-old diabetic female with right-side hemiparesis and aphasia occurring
      after a hypoglycemic episode is reported. Her clinical course improved over a 24
      hour period, and further investigation revealed only electroencephalographic
      slowing, which was more prominent on the left. Ten months later, she had a
      recurrence of the same symptoms, which also resolved rapidly. This potential
      complication of hypoglycemia is often mistaken for a cerebrovascular accident.

PMID- 11516617
TI  - Postvaricella angiopathy: report of a case with pathologic correlation.
AB  - Varicella is a common childhood illness, and central nervous system complications
      occur frequently. Delayed angiopathy has been described, although there are few
      reports of clinicopathologic correlation. A previously well 4-year-old male is
      presented. He suffered varicella 2 months before presentation with extensive
      right middle cerebral artery (MCA) territory infarction. Cerebral angiography
      demonstrated an isolated 89% stenosis of the right proximal MCA. He developed
      cerebral edema refractory to medical treatment and progressed to transtentorial
      herniation. Right frontal temporoparietal craniotomies were performed with
      evacuation of infarcted brain tissue. Pathologic studies revealed small vessel
      vasculitis with lymphocytic infiltration of the vessel wall. Areas of
      demyelination were present within the white matter. Polymerase chain reaction for
      varicella was negative on brain tissue. Postvaricella angiopathy, although an
      uncommon complication, may affect both small and large blood vessels, with
      catastrophic results.

PMID- 11516618
TI  - Primary leptomeningeal melanoma in a child.
AB  - Primary malignant melanoma of the leptomeninges is a rare and aggressive tumor in
      children and accounts for less than 1% of all pediatric malignancies. Usually its
      symptoms include raised intracraneal pressure resulting from hydrocephalus
      secondary to tumoral obliteration of basal cisterns, but the passage of time from
      the initial symptomatology to diagnosis is frequently delayed. A 7-year-old male
      with primary leptomeningeal melanoma is reported. At the beginning, he presented
      ataxia and dysarthria followed by symptoms of raised intracranial pressure,
      complex partial seizures, progressive loss of consciousness, and coma.
      Cerebrospinal fluid analysis demonstrated raised opening pressure, normal
      glucose, and increased protein concentration, but malignant melanoma cells were
      not found. Magnetic resonance imaging scans depicted bright signals in the
      subarachnoid spaces on T(1) images and gadolinium-enhanced focal lesions.
      Cerebral biopsy was proposed, but it was not authorized. Definitive diagnosis was
      thus made by pathologic postmortem examination.

PMID- 11516619
TI  - MRI follow-up of basal ganglia involvement in subacute sclerosing
      panencephalitis.
AB  - A 12-year-old male with subacute sclerosing panencephalitis is presented.
      Magnetic resonance imaging revealed basal ganglia involvement without white
      matter changes for several months. Basal ganglia changes are not infrequent in
      subacute sclerosing panencephalitis, but they tend to appear in advanced clinical
      stages. Prominent basal ganglia involvement may occur very rarely in subacute
      sclerosing panencephalitis. In our patient, serial magnetic resonance imaging
      demonstrated the involvement of white matter after 2 years of magnetic resonance
      imaging follow-up. In contrast with the neuroradiologic progression, our
      patient's clinical status remained stable.

PMID- 11516620
TI  - Crosstalk and specificity in signalling. Are we crosstalking ourselves into
      general confusion?
AB  - The numerous examples of "crosstalk" between signal transduction pathways
      reported in the biochemical literature seem to imply a general common response of
      cells to different stimuli, even when these stimuli act initially on different
      cascades. This contradicts our knowledge of the specificity of action of
      extracellular signals in different cell types. This discrepancy is explained by
      the restricted occurrence of crosstalks in any cell type and by several
      categories of cell specificity mechanisms, for instance, the specific qualitative
      and quantitative expression of the various subtypes of signal transduction
      proteins, the combinatorial control of the cascades with specific sets of
      regulatory factors and the compartmentation of signal transduction cascades or
      their elements.

PMID- 11516621
TI  - Modulation by propranolol of the uptake of ethidium bromide by rat submandibular
      acinar cells exposed to a P2X(7) agonist or to maitotoxin.
AB  - We have compared the formation of pores in rat submandibular acinar cells in
      response to 2',3'-O-(4-benzoylbenzoyl) adenosine 5'-triphosphate (Bz-ATP) and
      maitotoxin. Bz-ATP (100 microM) permeabilized the cells to ethidium bromide. The
      uptake of ethidium increased to 29+/-1% of maximal uptake in 10 min. DL
      Propranolol (300 microM) inhibited the Bz-ATP-induced uptake of ethidium bromide
      by 40% without affecting the P2X(7)-gated cation channel. The inhibitory effect
      of DL-propranolol on the formation of pores by Bz-ATP was reproduced by D
      propranolol, an optical isomer with very poor beta-blocking activity. Tenidap, an
      antiinflammatory drug, enhanced the permeabilization in response to Bz-ATP.
      Propanolol inhibited the response to tenidap plus Bz-ATP. The effect of
      propranolol was reproduced by labetolol, a beta-adrenergic antagonist with
      membrane-stabilizing properties, but not by atenolol, which blocks beta
      adrenergic receptors but has no effect on the stability of the membrane. In the
      presence of extracellular calcium, maitotoxin also increased the uptake of
      ethidium bromide. Tenidap had no effect on this response, which was delayed by
      propranolol. In conclusion, we have shown that propranolol, in a range of 10-300
      microM, inhibits the pore-forming activity of the P2X(7) receptor without
      affecting the opening of the cation channel coupled to this receptor. This
      inhibition is not related to its beta-adrenergic blocking activity but rather to
      its membrane-stabilizing properties. Propranolol also delays the uptake of
      ethidium bromide in response to maitotoxin. This is in agreement with the current
      view that P2X(7) agonists and maitotoxin share a common pore.

PMID- 11516622
TI  - Membrane-targeting is critical for the phosphorylation of Vav2 by activated EGF
      receptor.
AB  - Vav2 is a member of the Vav family that serves as guanine nucleotide exchange
      factors (GEFs) for the Rho family of Ras-related GTPases. Unlike Vav1, whose
      expression is restricted to cells of hematopoietic origin, Vav2 is broadly
      expressed. Recently, Vav2 has been identified as a substrate for the EGF
      receptor. Here, we show that in EGF-treated COS7 cells Vav2 is phosphorylated on
      tyrosine residues and associates with the EGF receptor. In addition, introducing
      point mutations into the SH2 domain of green fluorescens protein (GFP)-Vav2
      fusion protein leads to the loss of Vav2 tyrosine phosphorylation in response to
      EGF. To investigate further the mechanism of Vav2 phosphorylation, N-terminal
      (NT) domain of Vav2 was transiently expressed in COS7 cells as GFP fusion
      protein. Whereas the NT domain of Vav2 is a preferred substrate for the activated
      EGF receptor in vitro, we could not detect tyrosine phosphorylation of the GFP-NT
      construct in EGF-treated cells. However, when the SH2 domain of Vav2 was fused to
      its NT domain, NT domain proved to be a substrate for the EGF receptor in vivo.
      These data suggest that membrane-targeting of Vav2 through its SH2 domain is an
      important event in the phosphorylation and activation of Vav2 in response to EGF.

PMID- 11516623
TI  - Transforming growth factor-beta-mediated mast cell migration depends on mitogen
      activated protein kinase activity.
AB  - Transforming growth factor-beta (TGF-beta) isoforms regulate numerous cellular
      functions through binding to receptors with intrinsic serine/threonine kinase
      activity that transduce the intracellular signals via activation of Smad
      proteins. In this study, we examined the signalling pathways involved in TGF
      beta1-mediated growth inhibition and migration in a human mast cell line, HMC-1.
      TGF-beta1 evoked optimal migration at 40 fM, whereas maximal growth inhibition
      was obtained at 400 pM. Protein tyrosine kinase inhibitors completely inhibited
      TGF-beta1-mediated migration, without affecting the antimitogenic response. Smad2
      was phosphorylated upon TGF-beta1 treatment, both in the absence and presence of
      genistein. The mitogen-induced extracellular kinase (MEK) inhibitor, PD98059,
      blocked the migratory response without affecting growth inhibition. In contrast,
      the p38 MAP kinase inhibitor, SB203580, had no significant effect on either
      migration or growth inhibition. These results indicate that different signalling
      pathways mediate TGF-beta1-induced migration and growth inhibition in HMC-1
      cells, where the migration involves MEK activity.

PMID- 11516624
TI  - Endothelin-1 increases glucose transporter glut1 mRNA accumulation in 3T3-L1
      adipocytes by a mitogen-activated protein kinase-dependent pathway.
AB  - The mechanism of enhancing glucose transport by prolonged endothelin-1 (ET-1)
      treatment of 3T3-L1 adipocytes was examined. Western and Northern blot analyses
      indicated that ET-1 increased the amount of both GLUT1 protein and mRNA. The
      degradation rate of GLUT1 mRNA as measured in the presence of actinomycin D,
      nevertheless, was not significantly altered by ET-1. Whereas various inhibitors
      for distinct signalling pathways were tested, only the mitogen-activated protein
      kinase (MAPK) kinase inhibitor, PD98059, was found to decrease significantly the
      enhancing effect of ET-1. Similar extent of inhibition was observed in cells
      pretreated with pertussis toxin (PT). Immunoblot analysis revealed that ET-1 may
      stimulate a transient phosphorylation of p42/p44 MAPK and both PT and PD98059
      inhibited this stimulation. In addition, the effect of ET-1 on GLUT1 mRNA
      accumulation was inhibited by PD98059 and cycloheximide, implying that a trans
      activation was involved. Taken together, these results suggest that ET-1 may
      induce GLUT1 gene expression by a MAPK-dependent mechanism.

PMID- 11516625
TI  - Down-regulation of growth factor-stimulated MAP kinase signaling in cytotoxic
      drug-resistant human neuroblastoma cells.
AB  - The mitogen-activated protein kinase (MAPk) signaling pathway, which plays a
      critical role in the proliferation of mammalian cells, is frequently up-regulated
      in human tumors and may contribute to the transformed phenotype. Since a major
      limitation of current cancer chemotherapy is prevalent resistance to cytotoxic
      drugs, this study determined whether alterations in growth factor signaling
      through MAPk may contribute to this phenomenon in human neuroblastoma cell lines.
      Drug-resistant SKNSH cell lines were established by long-term incubation with
      increasing concentrations to 10(-6) M doxorubicin (SKNSH rDOX6) or MDL 28842
      (SKNSH rMDL6). The expression of epidermal growth factor receptor (EGFR) and
      epidermal growth factor (EGF)-induced EGFR tyrosine phosphorylation were lower in
      drug-resistant SKNSH cells than their wild-type counterparts. In SKNSH rDOX6
      cells, decreased activation and reduced nuclear translocation of MAPk in response
      to EGF, or lysophosphatidic acid (LPA), or phorbol 12-myristate 13-acetate (PMA),
      were observed. In SKNSH rMDL6 cells, although MAPk could be activated to wild
      type levels by ligand stimulation, the translocation of active MAPk to the
      nucleus was also reduced. These results suggest that resistance to cytotoxic
      drugs in human neuroblastoma cell lines is associated with a decrease in growth
      factor signaling through the MAPk pathway.

PMID- 11516626
TI  - Identification of a surface on the beta-propeller protein RACK1 that interacts
      with the cAMP-specific phosphodiesterase PDE4D5.
AB  - A strategy of mutagenesis followed by yeast two-hybrid assay was used to
      determine the sites on the WD-repeat protein Receptor for Activated C Kinase 1
      (RACK1) necessary for it to interact with the cAMP-specific phosphodiesterase
      isoform PDE4D5. Analysis of deletion mutations demonstrated that WD-repeats 5-7,
      inclusively, of RACK1 contained the major site for interaction with PDE4D5. A
      reverse two-hybrid screen focusing on WD-repeats 5-7 of RACK1 isolated 11 single
      amino acid mutations from within this region that blocked the interaction. The
      ability of these mutations to block the interaction was confirmed by "pull-down"
      assays using bacterially expressed glutathione-S-transferase (GST)-RACK1 and
      mammalian cell-expressed PDE4D5. A model of RACK1 structure, based on the
      structural similarity of RACK1 to other beta-propeller WD-repeat proteins,
      indicated that the majority of the amino acids identified by mutagenesis are
      clustered in a discrete surface of RACK1. We propose that this surface of RACK1
      is the major site for its interaction with the unique amino-terminal region of
      PDE4D5.

PMID- 11516627
TI  - Ouabain-induced enhancement of rat mast cells response. Modulation by protein
      phosphorylation and intracellular pH.
AB  - The digitalic glicoside ouabain induces potentiation of rat mast cell histamine
      release in response to several stimuli, which is mediated by Na+/Ca2+ exchanger.
      In this work, we studied the effect of ouabain on cytosolic calcium,
      intracellular pH and histamine release with Ca2+ ionophore A23187 in conditions
      designed to maximize ouabain-induced potentiation of rat mast cells response. The
      effect of protein kinase C (PKC), cAMP and phosphatase inhibition was also
      tested. Ouabain induced an enhancement in histamine release, cytosolic calcium
      and intracellular pH. The adenylate cyclase activator forskolin reduced the
      effect of ouabain on histamine release and intracellular pH, but enhanced the
      effect on cytosolic calcium. PKC activator PMA enhanced the effect of ouabain on
      histamine release and cytosolic calcium, without affecting intracellular pH. A
      PKC inhibitor, GF-109203X, reduced ouabain-induced enhancement of histamine
      release and intracellular pH, but increased the enhancement on cytosolic calcium.
      Finally, inhibition of protein phosphatases 1 and 2A with okadaic acid, increased
      the effect of ouabain on histamine release and intracellular pH, but reduced
      cytosolic calcium in presence of ouabain. This result suggest that ouabain
      induced potentiation of rat mast cell histamine release with A23187 is modulated
      by kinases, and this modulation may be carried out by changes in intracellular
      alkalinization. However, the mechanism underlying cellular alkalinization remains
      to be elucidated.

PMID- 11516628
TI  - Ultrasound and Power Doppler findings in jumper's knee - preliminary
      observations.
AB  - OBJECTIVE: to examine a group of high risk athletes, for signs of inflammation in
      jumper's knee (JK) by gray-scale ultrasonography (US) and color/Power Doppler
      findings in JK. SUBJECTS AND METHODS: eighteen high-elite basketball players
      participated in the investigation after a match. Seven players were examined by
      ultrasound before the match as well. The players were clinically examined for
      signs of JK and filled in a questionnaire concerning previous and present knee
      symptoms. RESULTS: clinical signs of JK were found in 13 knees. Of these knees,
      ten had hypoechoic areas and six had Power Doppler flow. Four players reported
      symptoms of JK and clinical examination suspected the same. Three of them had
      both hypoechoic areas and Power Doppler flow. Fourteen players were asymptomatic
      at the time of examination but both hypoechoic areas and Power Doppler flow was
      found in the patellar tendons of four players. No correlation was found between
      clinical findings, symptoms of JK and US findings - including Power Doppler. The
      risk of type II error in this material is considerable. CONCLUSION: an
      association between gray-scale US and color/Power Doppler was found in JK which
      may suggest an inflammatory component to be a part of the pathogenesis of JK.

PMID- 11516629
TI  - Surface landmarks of brachial plexus: ultrasound and magnetic resonance imaging
      for supraclavicular approach with anatomical correlation.
AB  - The present study is able to describe a certain line, under which brachial plexus
      (BP) lies underneath in the supraclavicular region. A line drawn between midpoint
      of the sternocleidomastoid muscle to the midpoint of the clavicle was considered
      for BP. Surface landmarks were evaluated by applying ultrasound (US) on 30
      volunteers (15 female, 15 male). Axial and sagittal views of BP were taken and
      distances between skin and BP were measured. Coronal magnetic resonance (MR)
      sections were taken from 7 volunteers according to the second line after applying
      two fat capsules on each line. The sonographic views were seen at the same line.
      Mean distances from skin were found as 16.5+/-0.7 mm for male and 14.5+/-0.5 mm
      for female volunteers. MR images were obtained bilaterally, which were parallel
      and posterior from sonographic lines. Surface landmarks, as presented in this
      study, are simple to accomplish and are not dependent on structural variations as
      external jugular vein.

PMID- 11516630
TI  - A case of phlegmonous gastritis diagnosed by echography.
AB  - Relying on their experience of revealing phlegmonous gastritis in a female
      patient aged 44, the authors suggest to use abdominal echography to diagnose this
      urgent condition in the screening of acute inflammatory abdominal diseases,
      leaning upon echographic evidence of hollow organ damages, which are noted in
      inflammatory and blastomatous gastric wall infiltration and leaving the last word
      to complete evaluation of clinical, echographic and laboratory data.

PMID- 11516631
TI  - Hyperechoic focal bacterial nephritis: findings on contrast-enhanced Colour
      Doppler ultrasound.
AB  - We report a case of atypical focal bacterial nephritis (lobar nephronia)
      simulating a renal mass on gray-scale ultrasound, describing the findings on
      Colour Doppler ultrasound before and after administration of a galactose-based
      ultrasound contrast agent.

PMID- 11516632
TI  - Quantification of gastric emptying and duodenogastric reflux stroke volumes using
      three-dimensional guided digital color Doppler imaging.
AB  - OBJECTIVE: To develop a non-invasive method for evaluating gastric emptying and
      duodenogastric reflux stroke volumes using three-dimensional (3D) guided digital
      color Doppler imaging. METHODS: The technique involved color Doppler digital
      images of transpyloric flow in which the 3D position and orientation of the
      images were known by using a magnetic location system. RESULTS: In vitro, the
      system was found to slightly underestimate the reference flow (by average 8.8%).
      In vivo (five volunteers), stroke volume of gastric emptying episodes lasted on
      average only 0.69 s with a volume on average of 4.3 ml (range 1.1-7.4 ml), and
      duodenogastric reflux episodes on average 1.4 s with a volume of 8.3 ml (range
      1.3-14.1 ml). CONCLUSION: With the appropriate instrument settings, orientation
      determined color Doppler can be used for stroke volume quantification of gastric
      emptying and duodenogastric reflux episodes.

PMID- 11516633
TI  - Use of thigh pressure cuffs to modulate simulated microgravity-induced changes in
      the skin measured with high-resolution B-scan ultrasound.
AB  - OBJECTIVE: The aim of the present study was to evaluate the fluid shift in a
      simulated microgravity experiment and to test the use of thigh cuffs to help
      alleviate the problem. METHODS: The change in skin thickness was assessed by a 20
      MHz B-scan ultrasound device. This was performed on eight volunteers who
      underwent two successive 7-day periods of -6 degrees anti-orthostatic bed-rest,
      with or without the daytime use of thigh cuffs. The thigh cuffs were used to
      counteract the development of facial oedema. RESULTS: In the control group
      (without thigh cuffs), the results showed a steady increase in skin thickness of
      the combined dermis and hypodermis of the forehead and a reduction of the
      thickness of this tissue on the tibia. For the countermeasure group, although
      thigh cuffs were only employed during the daytime - being removed at night -
      their use reduced the amplitude and kinetics of the fluid shift, resulting in
      greater beneficial effects at the end of the day than early in the morning.
      CONCLUSION: These results of objective measurements of skin made using a non
      invasive high frequency ultrasonography method confirm reports by cosmonauts of a
      reduction in facial oedema and a more 'comfortable' adaptation to microgravity by
      the use of thigh cuffs during space flight. This system is potentially promising
      for investigating fluid shifts in the skin and may prove useful in the evaluation
      of some oedematous skin diseases, as well as their therapy.

PMID- 11516634
TI  - EFSUMB reviews of safety literature: Recent epidemiology papers: European
      Committee for Medical Ultrasound Safety (ECMUS).

PMID- 11516635
TI  - Synergistic effect of tocotrienol-rich fraction (TRF(25)) of rice bran and
      lovastatin on lipid parameters in hypercholesterolemic humans.
AB  - Tocotrienols exert hypocholesterolemic action in humans and animals. Lovastatin
      is widely used for that purpose. Both agents work by suppressing the activity of
      beta-hydroxy-beta-methylglutaryl coenzyme A reductase through different
      mechanisms, post-transcriptional vs competitive inhibition. A human study with 28
      hypercholesterolemic subjects was carried out in 5 phases of 35 days each, to
      check the efficacy of tocotrienol-rich fraction (TRF(25)) of rice bran alone and
      in combination with lovastatin. After placing subjects on the American Heart
      Association (AHA) Step-1 diet (phase II), the subjects were divided into two
      groups, A and B. The AHA Step-1 diet was continued in combination with other
      treatments during phases III to V. Group A subjects were given 10 mg lovastatin,
      10 mg lovastatin plus 50 mg TRF(25), 10 mg lovastatin plus 50 mg alpha-tocopherol
      per day, in the third, fourth, and fifth phases, respectively. Group B subjects
      were treated exactly to the same protocol except that in the third phase, they
      were given 50 mg TRF(25) instead of lovastatin.The TRF(25) or lovastatin plus AHA
      Step-1 diet effectively lower serum total cholesterol (14%, 13%) and LDL
      cholesterol (18%, 15% P < 0.001), respectively, in hypercholesterolemic subjects.
      The combination of TRF(25) and lovastatin plus AHA Step-1 diet significantly
      reduces of these lipid parameters of 20% and 25% (P < 0.001) in these subjects.
      Substitution of TRF(25) with alpha-tocopherol produces insignificant changes when
      given with lovastatin. Especially significant is the increase in the HDL/LDL
      ratio to 46% in group (A) and 53% (P < 0.002) in group (B). These results are
      consistent with the synergistic effect of these two agents. None of the subjects
      reported any side-effects throughout the study of 25-weeks. In the present study,
      the increased effectiveness of low doses of tocotrienols (TRF(25)) as
      hypocholesterolemic agents might be due to a minimum conversion to alpha
      tocopherol. The report also describes in vivo the conversion of gamma-[4-3H]-,
      and [14C]-desmethyl (d-P(21)-T3) tocotrienols to alpha-tocopherol.

PMID- 11516636
TI  - Enteral infusion of phosphatidylcholine increases the lymphatic absorption of
      fat, but lowers alpha-tocopherol absorption in rats fed a low zinc diet*
AB  - Our previous study has shown that the lymphatic absorption of both fat and alpha
      tocopherol (alphaTP) is lowered markedly in rats fed a low zinc diet, with a
      parallel decrease in lymphatic phospholipid (PL) output. This study was conducted
      to determine if enteral infusion of phosphatidylcholine (PC) could restore
      lymphatic absorption of fat and alphaTP in zinc-deficient rats. One group of rats
      was fed an AIN-93G diet containing 3 mg Zn/kg (low zinc; LZ) and the other was
      fed the same diet but containing 30 mg Zn/kg (adequate zinc; AZ). Rats were
      trained to consume two meals daily of equal amounts of food. At 6 wk, each rat
      with lymph fistula was infused at 3 mL/h with a lipid emulsion containing 3.6
      &mgr;mol alphaTP and 565 &mgr;mol [carboxyl-14C]-triolein (14C-OA), with or
      without 40 &mgr;mol 1,2-dilinoleoyl-PC in 24 mL PBS at pH 6.4. The lymphatic
      absorptions of fat and alphaTP were determined by measuring 14C-radioactivity and
      alphaTP appearing in the mesenteric lymph collected hourly for 8 h. When the
      emulsion devoid of PC was infused, the absorptions of both 14C-OA (41 +/- 4%
      dose) and alphaTP (431 +/- 55 nmol) in LZ rats were significantly lower than in
      AZ rats (48 +/- 2% 14C-OA dose and 581 +/- 70 nmol alphaTP). When the emulsion
      containing PC was infused, the absorption of 14C-OA was restored rapidly to
      normal in LZ rats, along with a parallel increase in lymphatic PL output.
      However, PC infusion further lowered the absorption of alphaTP to 311 +/- 20
      nmol/8 h in LZ rats and also lowered the absorption of alphaTP in AZ rats (347 +/
      48 nmol/8 h). The results demonstrate that low zinc intake results in impaired
      intestinal absorption of both alphaTP and fat. The findings also indicate that PC
      significantly improves the intestinal absorption of fat, but inhibits alphaTP
      absorption, suggesting that PC affects the intestinal absorption of alphaTP and
      fat via distinctly different mechanisms.

PMID- 11516637
TI  - Protective effect of long term high fiber diet consumption on rat exocrine
      pancreatic function after chronic ethanol intake.
AB  - The effects of ethanol administration on exocrine pancreas have been widely
      studied, but little is known about the effect of dietary fiber in combination
      with chronic ethanol on exocrine pancreatic function. The aim of this work was to
      examine the chronic effects of a high fiber diet, ethanol ingestion, and a
      combination of both on the function of the rat exocrine pancreas. Four groups of
      rats were fed for six months the following diets: 1.- NW: standard laboratory
      diet; 2.- FW: high fiber diet (15% cellulose); 3.- NE: standard laboratory diet
      and 20% ethanol in the drinking water; and 4.- FE: high fiber diet and 20%
      ethanol. Cholecystokinin (CCK) and acetylcholine (Ach) effects on amylase release
      and intracellular calcium mobilization in pancreatic acini were studied. In rats
      fed a 20% ethanol (NE), both the basal amylase release and the basal [Ca(2+)](i)
      were significantly increased; nonetheless, CCK and Ach-induced amylase release
      were significantly reduced compared with control rats. Ach- but not CCK
      stimulated [Ca(2+)](i) increase in NE rats was significantly decreased compared
      with NW. In rats fed a combination of ethanol and a high fiber diet (FE) all the
      parameters under study were not significantly affected compared to control rats
      (NW). In conclusion, high fiber consumption does not alter the function of the
      exocrine pancreas. However, it ameliorates the deleterious effect of chronic
      ethanol consumption on pancreatic amylase secretion and, at least partially,
      reverses the ethanol-induced alterations on [Ca(2+)](i) in the rat exocrine
      pancreas.

PMID- 11516638
TI  - Quantitation of urinary 3-methylhistidine excretion in growing dogs as an index
      of in vivo skeletal muscle catabolism.
AB  - Purpose: To quantitate urinary 3-methylhistidine (3-mh) excretion as an index of
      in vivo muscle catabolism in dogs fed diets containing either normal or high
      protein levels.Methods: Twelve male, 5-month-old Beagle dogs were housed
      individually in metabolism cages and fed a non-meat, purified diet. They were
      divided into two diet groups of six dogs each, receiving 22.6% (NP) or 41.1% (HP)
      DM crude protein, respectively. Three dogs from each group received an
      intravenous injection of 385 +/- 29 kBq [14C] 3-mh. HCl. Urine and feces were
      collected daily until radioactivity returned to background levels (17 days).
      Urinary 3-mh was measured using an amino acid analyzer and percentage of bound 3
      mh was estimated via acid hydrolysis.Results: Results are reported as means +/-
      SEM. 3-mh recovery in urine and feces of dogs were 263 +/- 28 kBq and 50.7 +/-
      2.2 kBq and 327 +/- 45 kBq and 25.9 +/- 25.9 kBq for the NP and HP groups,
      respectively. The total cumulative 3-mh recoveries for the NP and HP groups were
      81.8% +/- 2.8 and 91.4% +/- 2.7, respectively. Bound 3-mh accounted for 2.1 to
      4.8% of urinary 14C-3-mh.Conclusions: Growing Beagle dogs excrete a higher
      percentage of 3-mh in feces (13.5% vs. 6.7%) when consuming the NP versus the HP
      diet. It appears that some of the 14C was lost in CO(2) and/or re-circulated in
      the body, as reported for sheep and pigs. We conclude that urinary 3-mh does not
      appear to be a quantitative index of in vivo muscle catabolism in growing dogs.

PMID- 11516639
TI  - Efficacy and safety of Touchi extract, an alpha-glucosidase inhibitor derived
      from fermented soybeans, in non-insulin-dependent diabetic mellitus.
AB  - The water-extracted Touchi, a traditional Chinese food, exerted a strong
      inhibitory activity against rat intestinal alpha-glucosidase in foodstuffs. In
      borderline and developed diabetic subjects, 0.3 g of Touchi-extract (TE)
      significantly inhibited postprandial blood glucose levels. For confirmation of
      safety, 9 healthy subjects were given 1 g of TE before every meal (3 g/day) for
      12 weeks. None indicated changes in hematological and relevant biochemical
      parameters, body weight or BMI. In a non-comparative study, 18 type-2 diabetic
      patients ingested 0.3 g of TE before every meal (0.9 g/day) for 6 months (mo).
      Blood glucose (mean; 9.31 +/- 0.71 mmol/L) and HbA(1c) (mean: 10.24 +/- 0.58%)
      levels gradually decreased, and significant effects were elicited on the blood
      glucose levels (8.61 +/- 0.66 mmol/L; p < 0.01) after 6 mo and HbA(1c) after 3
      (9.13 +/- 0.43%; p < 0.05) and 6 mo (8.96 +/- 0.30%; p < 0.05) post-ingestion of
      TE. Indexes for serum lipids and total cholesterol level revealed moderate
      decreases with a slight increase in the high-density lipoprotein (HDL) level
      after TE ingestion. However, triglyceride (TG) levels significantly decreased at
      3 (p < 0.05) and 6 mo (p < 0.01) post-ingestion of TE. In this study, other
      biochemical parameters were not affected in any of the patients, and no one
      complained of any side-effects or abdominal distension. TE, exhibiting alpha
      glucosidase inhibitory activity, demonstrated an anti-hyperglycemic effect and
      may prove useful for improving glycemic control in patients suffering from non
      insulin-dependent diabetic mellitus.

PMID- 11516640
TI  - Dietary oils high in oleic acid, but with different non-glyceride contents, have
      different effects on lipid profiles and peroxidation in rabbit hepatic
      mitochondria.
AB  - The influence on the lipid profile and lipid peroxidation in rabbit-liver
      mitochondria exerted by different edible oils high in oleic acid but different
      non-glyceride phenolic fractions was studied. High-phenolic virgin olive oil from
      the variety "Picual", the same oil submitted to an exhaustive process of washing
      to eliminate the phenolic fraction without altering the lipid profile and high
      oleic sunflower oil (poor in phenolic compounds) were added to rabbit diets. The
      results reveal the importance of the different oleic: linoleic ratio of the lipid
      sources on the lipid profile of mitochondrial membranes. This is highlighted by
      the greater proportion of saturated fatty acids and the lower content in oleic
      acid (p < 0.05) shown by the rabbits fed on high-oleic sunflower oil. The group
      fed on the fat rich in phenolics exhibited the highest level of antioxidants
      (alpha-tocopherol, ubiquinone 10) and the highest activity of glutathione
      peroxidase as well as the lowest content in hydroperoxides and TBARS. The study
      provides evidences in vivo about the considerable antioxidant capacity of the
      phenolic fraction of virgin olive oil in rabbit-liver mitochondria and the
      important role that this non-glyceride fraction can play in the overall
      antioxidant benefits attributed to this oil.

PMID- 11516641
TI  - Dietary fish oil prevents asynchronous contractility and alters Ca(2+) handling
      in adult rat cardiomyocytes.
AB  - This study examined the effects of dietary incorporation of n-3 polyunsaturated
      fatty acids (PUFAs) into cardiac membrane phospholipids on Ca(2+) handling (using
      Fura-2) and arrhythmic contractility in electrically-stimulated, adult rat
      ventricular cardiomyocytes. Dietary lipid supplementation with fish oil (FO) for
      3 weeks significantly increased the proportion of total n-3 polyunsaturated fatty
      acids (in particular, docosahexaenoic acid) in ventricular membrane phospholipids
      compared with a saturated fat (SF) supplemented diet (26.2 +/- 0.9% vs 6.9 +/-
      0.9%, respectively, P < 0.001). Cardiomyocytes isolated from the FO group were
      significantly (P < 0.001) less susceptible to isoproterenol-induced arrhythmic
      contractile activity compared with the SF group over a range of isoproterenol
      concentrations. Isoproterenol (0.5 &mgr;M) stimulation increased end-diastolic
      and systolic [Ca(2+)](i) to a similar extent in both groups. The time constant of
      Ca(2+) transient decay was significantly increased in the FO group compared with
      the SF group (98.4 +/- 2.8 ms, n = 8 and 86.9 +/- 2.1 ms, n = 8, P < 0.01,
      respectively). The effect of dietary n-3 PUFA incorporation into membrane
      phospholipids was not associated with changes in sarcoplasmic reticulum Ca(2+)
      content (measured by rapid application of caffeine) or membrane fluidity. The
      increase in the time constant of decay of Ca(2+) transients following dietary
      supplementation with FO may indicate altered functioning of the sarcolemmal Na(+)
      Ca(2+) exchanger by n-3 PUFA incorporation into membrane phospholipids.

PMID- 11516642
TI  - A reverse genetic analysis of components of the Toll signaling pathway in
      Caenorhabditis elegans.
AB  - BACKGROUND: Both animals and plants respond rapidly to pathogens by inducing the
      expression of defense-related genes. Whether such an inducible system of innate
      immunity is present in the model nematode Caenorhabditis elegans is currently an
      open question. Among conserved signaling pathways important for innate immunity,
      the Toll pathway is the best characterized. In Drosophila, this pathway also has
      an essential developmental role. C. elegans possesses structural homologs of
      components of this pathway, and this observation raises the possibility that a
      Toll pathway might also function in nematodes to trigger defense mechanisms or to
      control development. RESULTS: We have generated and characterized deletion
      mutants for four genes supposed to function in a nematode Toll signaling pathway.
      These genes are tol-1, trf-1, pik-1, and ikb-1 and are homologous to the
      Drosophila melanogaster Toll, dTraf, pelle, and cactus genes, respectively. Of
      these four genes, only tol-1 is required for nematode development. None of them
      are important for the resistance of C. elegans to a number of pathogens. On the
      other hand, C. elegans is capable of distinguishing different bacterial species
      and has a tendency to avoid certain pathogens, including Serratia marcescens. The
      tol-1 mutants are defective in their avoidance of pathogenic S. marcescens,
      although other chemosensory behaviors are wild type. CONCLUSIONS: In C. elegans,
      tol-1 is important for development and pathogen recognition, as is Toll in
      Drosophila, but remarkably for the latter role, it functions in the context of a
      behavioral mechanism that keeps worms away from potential danger.

PMID- 11516643
TI  - Spatially restricted expression of candidate taste receptors in the Drosophila
      gustatory system.
AB  - BACKGROUND: Taste is an important sensory modality in most animals. In
      Drosophila, taste is perceived by gustatory neurons located in sensilla
      distributed on several different appendages throughout the body of the animal.
      Here we show that the gustatory receptors are encoded by a family of at least 54
      genes (Gr genes), most of which are expressed exclusively in a small subset of
      taste sensilla located in narrowly defined regions of the fly's body. RESULTS:
      BLAST searches with the predicted amino acid sequences of 6 7-transmembrane
      receptor genes of unknown function and 20 previously identified, putative
      gustatory receptor genes led to the identification of a large gene family
      comprising at least 54 genes. We investigated the expression of eight genes by
      using a Gal4 reporter gene assay and found that five of them were expressed in
      the gustatory system of the fly. Four genes were expressed in 1%-4% of taste
      sensilla, located in well-defined regions of the proboscis, the legs, or both.
      The fifth gene was expressed in about 20% of taste sensilla in all major
      gustatory organs, including the taste bristles on the anterior wing margin. Axon
      tracing experiments demonstrated that neurons expressing a given Gr gene project
      their axons to a spatially restricted domain of the subesophageal ganglion in the
      fly brain. CONCLUSIONS: Our findings suggest that each taste sensillum represents
      a discrete, functional unit expressing at least one Gr receptor and that most Gr
      genes are expressed in spatially restricted domains of the gustatory system.
      These observations imply the potential for high taste discrimination of the
      Drosophila brain.

PMID- 11516644
TI  - Role of bud6p and tea1p in the interaction between actin and microtubules for the
      establishment of cell polarity in fission yeast.
AB  - BACKGROUND: In many cell types, microtubules are thought to direct the spatial
      distribution of F-actin in cell polarity. Schizosaccharomyces pombe cells exhibit
      a regulated program of polarized cell growth: after cell division, they grow
      first in a monopolar manner at the old end, and in G2 phase, initiate growth at
      the previous cell division site (the new end). The role of microtubule ends in
      cell polarity is highlighted by the finding that the cell polarity factor, tea1p,
      is present on microtubule plus ends and cell tips [1]. RESULTS: Here, we
      characterize S. pombe bud6p/fat1p, a homolog of S. cerevisiae Bud6/Aip3.
      bud6Delta mutant cells have a specific defect in the efficient initiation of
      growth at the new end and like tea1Delta cells, form T-shaped cells in a cdc11
      background. Bud6-GFP localizes to both cell tips and the cytokinesis ring.
      Maintenance of cell tip localization is dependent upon actin but not
      microtubules. Bud6-GFP localization is tea1p dependent, and tea1p localization is
      not bud6p dependent. tea1Delta and bud6Delta cells generally grow in a monopolar
      manner but exhibit different growth patterns. tea1(Delta)bud6Delta mutants
      resemble tea1Delta mutants. Tea1p and bud6p coimmunoprecipitate and comigrate in
      large complexes. CONCLUSIONS: Our studies show that tea1p (a microtubule end
      associated factor) and bud6p (an actin-associated factor) function in a common
      pathway, with bud6p downstream of tea1p. To our knowledge, bud6p is the first
      protein shown to interact physically with tea1p. These studies delineate a
      pathway for how microtubule plus ends function to polarize the actin cytoskeleton
      through actin-associated polarity factors.

PMID- 11516645
TI  - Nonmonotonic noise tuning of BOLD fMRI signal to natural images in the visual
      cortex of the anesthetized monkey.
AB  - BACKGROUND: The perceptual ability of humans and monkeys to identify objects in
      the presence of noise varies systematically and monotonically as a function of
      how much noise is introduced to the visual display. That is, it becomes more and
      more difficult to identify an object with increasing noise. Here we examine
      whether the blood oxygen level-dependent functional magnetic resonance imaging
      (BOLD fMRI) signal in anesthetized monkeys also shows such monotonic tuning. We
      employed parametric stimulus sets containing natural images and noise patterns
      matched for spatial frequency and intensity as well as intermediate images
      generated by interpolation between natural images and noise patterns.
      Anesthetized monkeys provide us with the unique opportunity to examine visual
      processing largely in the absence of top-down cognitive modulations and can thus
      provide an important baseline against which work with awake monkeys and humans
      can be compared. RESULTS: We measured BOLD activity in occipital visual cortical
      areas as natural images and noise patterns, as well as intermediate interpolated
      patterns at three interpolation levels (25%, 50%, and 75%) were presented to
      anesthetized monkeys in a block paradigm. We observed reliable visual activity in
      occipital visual areas including V1, V2, V3, V3A, and V4 as well as the fundus
      and anterior bank of the superior temporal sulcus (STS). Natural images
      consistently elicited higher BOLD levels than noise patterns. For intermediate
      images, however, we did not observe monotonic tuning. Instead, we observed a
      characteristic V-shaped noise-tuning function in primary and extrastriate visual
      areas. BOLD signals initially decreased as noise was added to the stimulus but
      then increased again as the pure noise pattern was approached. We present a
      simple model based on the number of activated neurons and the strength of
      activation per neuron that can account for these results. CONCLUSIONS: We show
      that, for our parametric stimulus set, BOLD activity varied nonmonotonically as a
      function of how much noise was added to the visual stimuli, unlike the perceptual
      ability of humans and monkeys to identify such stimuli. This raises important
      caveats for interpreting fMRI data and demonstrates the importance of assessing
      not only which neural populations are activated by contrasting conditions during
      an fMRI study, but also the strength of this activation. This becomes
      particularly important when using the BOLD signal to make inferences about the
      relationship between neural activity and behavior.

PMID- 11516646
TI  - Mammalian postmitotic nuclei reenter the cell cycle after serum stimulation in
      newt/mouse hybrid myotubes.
AB  - Cell cycle reentry and dedifferentiation of postmitotic cells are important
      aspects of the ability of an adult newt and other urodele amphibians to
      regenerate various tissues and appendages [1]. In contrast to their mammalian
      counterparts, newt A1 myotubes are able to reenter S phase after serum
      stimulation of a pathway leading to phosphorylation of the retinoblastoma
      protein, pRb [2]. The activity in serum is not due to mitogenic growth factors
      but is generated indirectly by the activation of thrombin and subsequent
      proteolysis [3]. In this paper we describe the formation of interspecies hybrid
      (heterokaryon) myotubes by the fusion of mouse C2C12 [4] and newt A1 [5, 6]
      myogenic cells. The C2C12 nuclei reenter the cell cycle upon serum stimulation of
      the hybrids, while C2C12 homokaryon myotubes remain arrested under these
      conditions. These findings indicate that the postmitotic arrest of the mouse
      nuclei is undermined by the pathway activated in the newt cytoplasm. The hybrid
      myotubes provide a new model for the manipulation of the postmitotic arrest in
      both mammalian and newt differentiated cells.

PMID- 11516647
TI  - Asymmetric colocalization of Flamingo, a seven-pass transmembrane cadherin, and
      Dishevelled in planar cell polarization.
AB  - The Drosophila wing provides an appropriate model system for studying genetic
      programming of planar cell polarity (PCP) [1-4]. Each wing cell respects the
      proximodistal (PD) axis; i.e., it localizes an assembly of actin bundles to its
      distalmost vertex and produces a single prehair. This PD polarization requires
      the redistribution of Flamingo (Fmi), a seven-pass transmembrane cadherin, to
      proximal/distal cell boundaries; otherwise, the cell mislocalizes the prehair
      [5]. Achievement of the biased Fmi pattern depends on two upstream components in
      the PCP signaling pathway: Frizzled (Fz), a receptor for a hypothetical polarity
      signal, and an intracellular protein, Dishevelled (Dsh) [6-8]. Here, we
      visualized endogenous Dsh in the developing wing. A portion of Dsh colocalized
      with Fmi, and the distributions of both proteins were interdependent.
      Furthermore, Fz controlled the association of Dsh with cell boundaries, which
      association was correlated with the presence of hyperphosphorylated forms of Dsh.
      Our results, together with a recent study on Fz distribution [9], support the
      possibility that Fz, Dsh, and Fmi constitute a signaling complex and that its
      restricted localization directs cytoskeletal reorganization only at the distal
      cell edge.

PMID- 11516648
TI  - A C. elegans orphan nuclear receptor contributes to xenobiotic resistance.
AB  - Lipophilic endocrine signals in metazoans, including the steroid, thyroid, and
      retinoid hormones, alter gene expression in target cells by binding to and
      modulating the activity of nuclear receptor (NR) transcription factors [1]. In
      vertebrates, xenobiotic and pharmacologic compounds can regulate the expression
      of protective metabolic enzymes via specific "xenobiotic sensing" NRs [2-4].
      Here, we report evidence suggesting that this activity is an ancient conserved
      function for the NR class containing these receptors. Specifically, we show that
      a Caenorhabditis elegans member of this NR class, nhr-8, is required for wild
      type levels of resistance to the toxins colchicine and chloroquine. The nhr-8
      promoter is active in the nematode gut, a tissue that also expresses the ABC
      transporter, PGP-3, which contributes to defense against these toxins [5]. In
      contrast to pgp-3 mutants, nhr-8 mutants are not more sensitive than wild-type to
      pyocyanin-dependent killing by the pathogenic bacterium Pseudomonas aeruginosa.
      We conclude that NHR-8 functions in the nematode xenobiotic defense system and
      that NHR-8 and PGP-3 have overlapping, but distinct, spectra of toxin
      specificity.

PMID- 11516649
TI  - Crosstalk between ARF6 and protein kinase Calpha in Fc(gamma)RI-mediated
      activation of phospholipase D1.
AB  - Fc receptors play a pivotal role linking the cellular and humoral arms of the
      immune system [1-3]. Our previous studies have shown that the human high-affinity
      immunoglobulin G receptor Fc(gamma)RI couples to a novel intracellular signaling
      pathway requiring phospholipase D activation [4]. The mechanisms that regulate
      receptor coupling to phospholipase D in intact cells are poorly understood but
      involve small molecular weight GTPases and protein kinase C [5-7]. Here, we show
      that immune complex aggregation of Fc(gamma)RI stimulates the association of
      phospholipase D1 with ARF6 and protein kinase Calpha. Surprisingly, PKCalpha
      activity per se is not required. Rather, all of the Fc(gamma)RI-mediated increase
      in PKC activity requires phospholipase D1, as treatment of cells with butan-1-ol
      (0.3%) or specific downregulation of phospholipase D1 using antisense
      oligonucleotides inhibits Fc(gamma)RI-coupled PKC activation. Moreover, treatment
      of cells with butan-1-ol or phospholipase D1 antisense oligonucleotides inhibits
      translocation of PKCdelta, -epsilon, and -zeta but had no effect on the
      association of PKCalpha or ARF6 with phospholipase D1. These data indicate that
      association with ARF6 and PKCalpha plays a role in coupling Fc(gamma)RI to
      phospholipase D1 activation and that PLD1 lies upstream of all Fc(gamma)RI
      mediated PKC activity.

PMID- 11516650
TI  - Nef increases infectivity of HIV via lipid rafts.
AB  - Lipid rafts, also known as detergent-resistant membranes (DRM), are microdomains
      in the plasma membrane enriched in sphingolipids and cholesterol (reviewed in [1,
      2]). Human immunodeficiency virus 1 (HIV) buds via lipid rafts [3, 4]. However,
      the targeting of viral structural components to DRM and its consequences for
      viral replication are not understood. Moreover, the negative factor Nef from HIV
      increases viral infectivity (reviewed in [5, 6]). With no apparent differences in
      structural components and morphology between wild-type and DeltaNef virons, the
      latter viruses display less efficient reverse transcription in target cells. As
      Nef is expressed abundantly early in the viral replicative cycle [7], we
      hypothesized that Nef could affect viral morphogenesis and budding to render
      viruses more infectious. In this report, we demonstrated first that Nef increases
      viral budding from lipid rafts. Second, in the presence of Nef, viral envelopes
      contain more ganglioside (GM1), which is a major component of lipid rafts. This
      finding correlated directly with the increased infectivity of HIV. Finally, the
      depletion of exogenous and endogenous cholesterol biochemically and genetically,
      which disrupted lipid rafts, decreased viral infectivity only in the presence of
      Nef. Importantly, HIV lacking the nef gene remained unaffected by these
      manipulations. We conclude that lipids in virions are essential for viral
      infectivity. Thus, HIV becomes more infectious when it buds from lipid rafts, and
      Nef plays a major role in this process.

PMID- 11516651
TI  - Categorizing sex and identity from the biological motion of faces.
AB  - Head and facial movements can provide valuable cues to identity in addition to
      their primary roles in communicating speech and expression [1-8]. Here we report
      experiments in which we have used recent motion capture and animation techniques
      to animate an average head [9]. These techniques have allowed the isolation of
      motion from other cues and have enabled us to separate rigid translations and
      rotations of the head from nonrigid facial motion. In particular, we tested
      whether human observers can judge sex and identity on the basis of this
      information. Results show that people can discriminate both between individuals
      and between males and females from motion-based information alone. Rigid head
      movements appear particularly useful for categorization on the basis of identity,
      while nonrigid motion is more useful for categorization on the basis of sex.
      Accuracy for both sex and identity judgements is reduced when faces are presented
      upside down, and this finding shows that performance is not based on low-level
      motion cues alone and suggests that the information is represented in an object
      based motion-encoding system specialized for upright faces. Playing animations
      backward also reduced performance for sex judgements and emphasized the
      importance of direction specificity in admitting access to stored representations
      of characteristic male and female movements.

PMID- 11516652
TI  - INCENP is required for proper targeting of Survivin to the centromeres and the
      anaphase spindle during mitosis.
AB  - Three lines of investigation have suggested that interactions between Survivin
      and the chromosomal passenger proteins INCENP and Aurora-B kinase may be
      important for mitotic progression. First, interference with the function of
      Survivin/BIR1, INCENP, or Aurora-B kinase leads to similar defects in mitosis and
      cytokinesis [1-7] (see [8] for review). Second, INCENP and Aurora-B exist in a
      complex in Xenopus eggs [9] and in mammalian cultured cells [7]. Third,
      interference with Survivin or INCENP function causes Aurora-B kinase to be
      mislocalized in mitosis in both C. elegans and vertebrates [5, 7, 9]. Here, we
      provide evidence that Survivin, Aurora-B, and INCENP interact physically and
      functionally. Direct visualization of Survivin-GFP in mitotic cells reveals that
      it localizes identically to INCENP and Aurora-B. Survivin binds directly to both
      Aurora-B and INCENP in yeast two-hybrid and in vitro pull-down assays. The in
      vitro interaction between Survivin and Aurora-B is extraordinarily stable in that
      it resists 3 M NaCl. Finally, Survivin and INCENP interact functionally in vivo;
      in cells in which INCENP localization is disrupted, Survivin adheres to the
      chromosomes and no longer concentrates at the centromeres or transfers to the
      anaphase spindle midzone. Our data provide the first biochemical evidence that
      Survivin can interact directly with members of the chromosomal passenger complex.

PMID- 11516653
TI  - The Abl interactor proteins localize to sites of actin polymerization at the tips
      of lamellipodia and filopodia.
AB  - Cell movement is mediated by the protrusion of cytoplasm in the form of sheet-
      and rod-like extensions, termed lamellipodia and filopodia. Protrusion is driven
      by actin polymerization, a process that is regulated by signaling complexes that
      are, as yet, poorly defined. Since actin assembly is controlled at the tips of
      lamellipodia and filopodia [1], these juxtamembrane sites are likely to harbor
      the protein complexes that control actin polymerization dynamics underlying cell
      motility. An understanding of the regulation of protrusion therefore requires the
      characterization of the molecular components recruited to these sites. The Abl
      interactor (Abi) proteins, targets of Abl tyrosine kinases [2-4], have been
      implicated in Rac-dependent cytoskeletal reorganization in response to growth
      factor stimulation [5]. Here, we describe the unique localization of Abi proteins
      in living, motile cells. We show that Abi-1 and Abi-2b fused to enhanced yellow
      fluorescent protein (EYFP) are recruited to the tips of lamellipodia and
      filopodia. We identify the targeting domain as the homologous N terminus of these
      two proteins. Our findings are the first to suggest a direct involvement of
      members of the Abi protein family in the control of actin polymerization in
      protrusion events, and establish the Abi proteins as potential regulators of
      motility.

PMID- 11516654
TI  - Phosphorylation of threonine 156 of the mu2 subunit of the AP2 complex is
      essential for endocytosis in vitro and in vivo.
AB  - The clathrin-coated pit is the major port of entry for many receptors and
      pathogens and is the paradigm for membrane-based sorting events in higher cells
      [1]. Recently, it has been possible to reconstitute in vitro the events leading
      to assembly, invagination, and budding off of clathrin-coated vesicles, allowing
      dissection of the machinery required for sequestration of receptors into these
      structures [2-6]. The AP2 adaptor complex is a key element of this machinery
      linking receptors to the coat lattice, and it has previously been reported that
      AP2 can be phosphorylated both in vitro and in vivo [7-10]. However, the
      physiological significance of this has never been established. Here, we show that
      phosphorylation of a single threonine residue (Thr156) of the mu2 subunit of the
      AP2 complex is essential for efficient endocytosis of transferrin both in an in
      vitro coated-pit budding assay and in living cells.

PMID- 11516655
TI  - Bazooka and PAR-6 are required with PAR-1 for the maintenance of oocyte fate in
      Drosophila.
AB  - The anterior-posterior axis of C. elegans is defined by the asymmetric division
      of the one-cell zygote, and this is controlled by the PAR proteins, including PAR
      3 and PAR-6, which form a complex at the anterior of the cell, and PAR-1, which
      localizes at the posterior [1-4]. PAR-1 plays a similar role in axis formation in
      Drosophila: the protein localizes to the posterior of the oocyte and is necessary
      for the localization of the posterior and germline determinants [5, 6]. PAR-1 has
      recently been shown to have an earlier function in oogenesis, where it is
      required for the maintenance of oocyte fate and the posterior localization of
      oocyte-specific markers [7, 8]. Here, we show that the homologs of PAR-3
      (Bazooka) and PAR-6 are also required to maintain oocyte fate. Germline clones of
      mutants in either gene give rise to egg chambers that develop 16 nurse cells and
      no oocyte. Furthermore, oocyte-specific factors, such as Orb protein and the
      centrosomes, still localize to one cell but fail to move from the anterior to the
      posterior cortex. Thus, PAR-1, Bazooka, and PAR-6 are required for the earliest
      polarity in the oocyte, providing the first example in Drosophila where the three
      homologs function in the same process. Although these PAR proteins therefore seem
      to play a conserved role in early anterior-posterior polarity in C. elegans and
      Drosophila, the relationships between them are different, as the localization of
      PAR-1 does not require Bazooka or PAR-6 in Drosophila, as it does in the worm.

PMID- 11516657
TI  - Stem cell hopes fuel policy woes.

PMID- 11516658
TI  - Pluripotent politics.

PMID- 11516659
TI  - Tapping into genome secrets.

PMID- 11516661
TI  - Telomeres.

PMID- 11516662
TI  - Motile organelles: the importance of specific tubulin isoforms.
AB  - The requirements for building flagellar axonemes and centrioles are beginning to
      be uncovered. The carboxyl terminus of a specific beta tubulin isoform plays an
      important role in forming the '9 + 2' structure of the axoneme; delta tubulin
      plays an essential role in forming the triplet microtubules of centrioles and
      basal bodies.

PMID- 11516663
TI  - Plant cytokinesis: KNOLLE joins the club.
AB  - Dividing plant cells assemble a new intracellular compartment, the cell plate,
      which grows centrifugally by vesicle fusion to partition the cytoplasm. Genetic
      studies in Arabidopsis are revealing the molecular signals that specify this
      special membrane transport pathway.

PMID- 11516664
TI  - Time perception: brain time or event time?
AB  - Recent experiments show that synchronous events can appear to an observer to
      occur at different times. Neural processing time delays are offered as an
      explanation of these temporal illusions, but equating perceived time with
      processing time leads to some thorny philosophical problems.

PMID- 11516665
TI  - Protein destruction: adapting roles for Cks proteins.
AB  - Cks1, a subunit of cyclin-dependent kinases, has now been identified as an
      essential cofactor in the ubiquitination of the Cdk inhibitor p27 by the
      SCF(Skp2) ubiquitin ligase. This activity, which can be independent of Cdk
      binding, links Cks to positive growth control pathways regulating the G1/S
      transition and to cancer.

PMID- 11516666
TI  - Cell growth: the power of symplastic isolation.
AB  - Cotton (Gossypium hirsutum) fibers are single-celled seed coat hairs that
      elongate up to 2mm per day during a phase of rapid growth. Recent evidence
      suggests this growth is orchestrated by a series of events which includes
      temporary closure of plasmodesmata.

PMID- 11516667
TI  - Evolution: towards a genetical theory of adaptation.
AB  - The population genetic basis for adaptation has remained obscure despite a
      longstanding body of theory. Microbial selection experiments are beginning to
      provide some answers.

PMID- 11516668
TI  - Cell cycle: connecting DNA replication to sporulation in Bacillus.
AB  - Checkpoints have been a staple of eukaryotic cell cycle research for the past
      decade, but little is known about checkpoints in prokaryotes. New work on
      sporulation in Bacillus fills that gap by showing that such control systems
      function to coordinate aspects of the bacterial cell cycle.

PMID- 11516669
TI  - Lipid droplets: proteins floating on a pool of fat.
AB  - Proteins on the surface of lipid storage droplets are crucial to droplet
      structure and function, but are poorly understood. Recent reports reveal a
      function for perilipins, major lipid droplet proteins in adipocytes, and show
      that caveolin proteins can accumulate on lipid droplets.

PMID- 11516690
TI  - Receptor 1980 and Receptor 2000: twenty years of progress in receptor-binding
      radiotracers.

PMID- 11516691
TI  - The physical chemistry of ligand-receptor binding identifies some limitations to
      the analysis of receptor images.
AB  - The biophysical chemistry of ligand-receptor interactions imposes some
      restrictions on the characteristics of a radioligand if it is to be a useful
      tracer for accurately measuring the in vivo concentration of a specific cellular
      membrane receptor. This review discusses thermodynamic and kinetic rate constant
      considerations in selecting a ligand for radiolabeling and imaging. When
      radioligands of only modest specific activity are injected, one is able to use
      kinetic analysis to calculate the rate constant for the bimolecular binding
      reaction as well as the receptor concentration. Images of regional receptor
      density can be constructed from analysis of emission imaging data when the
      binding occurs at a rate that is slower than the collision frequency. A tracer
      that reacts with each collision cannot distinguish receptor density from blood
      flow. The theory of diffusion-limited reactions is reviewed and individual ligand
      receptor examples are presented to demonstrate conditions where, even for very
      fast forward reactions, the binding of radioligand to receptor is controlled by
      local biochemistry rather than by the purely physical process of diffusion.

PMID- 11516692
TI  - Radiolabeled muscarinic radioligands for in vivo studies.

PMID- 11516693
TI  - [(99m)Tc]MAG(3)-mannosyl-dextran: a receptor-binding radiopharmaceutical for
      sentinel node detection.
AB  - Technetium-99m-labeled benzoyl-mercaptoacetylglycylglycyl-glycine-mannosyl
      dextran ([(99m)Tc]MAG(3)-mannosyl-dextran) is a receptor-binding radiotracer that
      binds to mannose-binding protein, a receptor expressed by recticuloendothelial
      tissue. This agent is composed of a 10.5-kilodalton molecule of dextran and
      multiple units of mannose, and benzoyl-mercaptoacetylglycylglycyl-glycine
      (BzMAG(3)). The tetraflorophenol-activated ester of BzMAG(3) and the imidate of
      thiomannose were used to covalently attach BzMAG(3) and mannose to an amino
      terminated conjugate of dextran. This yielded a 19-kilodalton macromolecule
      consisting of 3 BzMAG(3) and 21 mannose units per dextran. Dynamic light
      scattering was used to measure a mean diameter of 5.5 nanometers for BzMAG(3)
      mannosyl-dextran and 0.28 microns for filtered Tc-99m sulfur colloid. A
      preliminary sentinel node detection study employing right fore and hind footpad
      injections of [(99m)Tc]MAG(3)-mannosyl-dextran and left fore and hind footpad
      injections of filtered Tc-99m sulfur colloid demonstrated greater sentinel lymph
      node uptake by the receptor-binding agent.

PMID- 11516694
TI  - The evolution of (99m)Tc-NGA as a clinically useful receptor-binding
      radiopharmaceutical.

PMID- 11516695
TI  - Development of Tc-99m labeled tropanes: TRODAT-1, as a dopamine transporter
      imaging agent.
AB  - Advances in the technetium chemistry have significantly enhanced the development
      of Tc-99m radiopharmaceuticals for clinical use. Efforts in designing novel Tc
      99m labeled receptor or site-specific imaging agents using [Tc(v)O](+3)N(2)S(2)
      core have produced useful imaging agents for single photo emission computed
      tomography (SPECT). The success in developing Tc-99m TRODAT-1 for CNS dopamine
      transporters (DAT) serves as the first example of Tc-99m site-specific imaging of
      human brain. New innovative Tc-99m labeled site-specific agents are particularly
      suitable to develop simple and useful routine diagnostic procedures.

PMID- 11516696
TI  - PET imaging of the opioid receptor: the early years.

PMID- 11516697
TI  - Radiolabeled peptide ligands for imaging thrombi and emboli.

PMID- 11516698
TI  - Radiometallated receptor-avid peptide conjugates for specific in vivo targeting
      of cancer cells.
AB  - New receptor-avid radiotracers are being developed for site-specific in vivo
      targeting of a myriad of receptors expressed on cancer cells. This review
      exemplifies strategies being used to design radiometallated peptide conjugates
      that maximize uptake in tumors and optimize their in vivo pharmacokinetic
      properties. Efforts to produce synthetic peptide analogues that target the
      following three receptor systems are highlighted: Gastrin releasing peptide
      (GRP), alpha-melanocyte stimulating hormone (alpha-MSH), and guanylate cyclase-C
      (GC-C) receptors.

PMID- 11516699
TI  - Assessment of cardiac sympathetic nerve integrity with positron emission
      tomography.
AB  - The autonomic nervous system plays a critical role in the regulation of cardiac
      function. Abnormalities of cardiac innervation have been implicated in the
      pathophysiology of many heart diseases, including sudden cardiac death and
      congestive heart failure. In an effort to provide clinicians with the ability to
      regionally map cardiac innervation, several radiotracers for imaging cardiac
      sympathetic neurons have been developed. This paper reviews the development of
      neuronal imaging agents and discusses their emerging role in the noninvasive
      assessment of cardiac sympathetic innervation.

PMID- 11516700
TI  - [(11)]Cocaine: PET studies of cocaine pharmacokinetics, dopamine transporter
      availability and dopamine transporter occupancy.
AB  - Cocaine was initially labeled with carbon-11 in order to track the distribution
      and pharmacokinetics of this powerful stimulant and drug of abuse in the human
      brain and body. It was soon discovered that [(11)C]cocaine was not only useful
      for measuring cocaine pharmacokinetics and its relationship to behavior but that
      it is also a sensitive radiotracer for dopamine transporter (DAT) availability.
      Measures of DAT availability were facilitated by the development of a graphical
      analysis method (Logan Plot) for reversible systems which streamlined kinetic
      analysis. This expanded the applications of [(11)C]cocaine to studies of DAT
      availability in the human brain and allowed the first comparative measures of the
      degree of DAT occupancy by cocaine and another stimulant drug methylphenidate.
      This article will summarize preclinical and clinical research with
      [(11)C]cocaine.

PMID- 11516701
TI  - Receptor binding radiotracers: personal history of the past 20 years.

PMID- 11516702
TI  - The biological application of small animal PET imaging.
AB  - The short history of small animal PET is reviewed in the context of its
      application in the laboratory. Early work has demonstrated a role for the
      technique in both drug development and in the in vivo monitoring of neuroreceptor
      function with time. As spatial resolution approaches 1 mm, challenges in
      quantification remain. However, the ability to carry out animal PET studies that
      are analogous to human PET will form an important bridge between laboratory and
      clinical sciences.

PMID- 11516703
TI  - Models and methods for derivation of in vivo neuroreceptor parameters with PET
      and SPECT reversible radiotracers.
AB  - The science of quantitative analysis of PET and SPECT neuroreceptor imaging
      studies has grown considerably over the past decade. A number of methods have
      been proposed in which receptor parameter estimation results from fitting data to
      a model of the underlying kinetics of ligand uptake in the brain. These
      approaches have come to be collectively known as model-based methods and several
      have received widespread use. Here, we briefly review the most frequently used
      methods and examine their strengths and weaknesses. Kinetic modeling is the most
      direct implementation of the compartment models, but with some tracers accurate
      input function measurement and good compartment configuration identification can
      be difficult to obtain. Other methods were designed to overcome some particular
      vulnerability to error of classical kinetic modeling, but introduced new
      vulnerabilities in the process. Reference region methods obviate the need for
      arterial plasma measurement, but are not as robust to violations of the
      underlying modeling assumptions as methods using the arterial input function.
      Graphical methods give estimates of V(T) without the requirement of compartment
      model specification, but provide a biased estimator in the presence of
      statistical noise. True equilibrium methods are quite robust, but their use is
      limited to experiments with tracers that are suitable for constant infusion. In
      conclusion, there is no universally "best" method that is applicable to all
      neuroreceptor imaging studies, and carefully evaluation of model-based methods is
      required for each radiotracer.

PMID- 11516704
TI  - Non-rigid registration by geometry-constrained diffusion.
AB  - Assume that only partial knowledge about a non-rigid registration is given:
      certain points, curves or surfaces in one 3D image are known to map to certain
      points, curves or surfaces in another 3D image. In trying to identify the non
      rigid displacement field, we face a generalized aperture problem since along the
      curves and surfaces, point correspondences are not given. We will advocate the
      viewpoint that the aperture and the 3D interpolation problem may be solved
      simultaneously by finding the simplest displacement field. This is obtained by a
      geometry-constrained diffusion, which in a precise sense yields the simplest
      displacement field. The point registration obtained may be used for segmentation,
      growth modeling, shape analysis or kinematic interpolation. The algorithm applies
      to geometrical objects of any dimensionality. We may thus keep any number of
      fiducial points, curves and/or surfaces fixed while finding the simplest
      registration. Examples of inferred point correspondences in a synthetic example
      and a longitudinal growth study of the human mandible are given.

PMID- 11516705
TI  - Evaluation of using absolute versus relative base level when analyzing brain
      activation images using the scale-space primal sketch.
AB  - A dominant approach to brain mapping is to define functional regions in the brain
      by analyzing images of brain activation obtained from positron emission
      tomography (PET) and functional magnetic resonance imaging (fMRI). This paper
      presents an evaluation of using one such tool, called the scale-space primal
      sketch, for brain activation analysis. A comparison is made concerning two
      possible definitions of a significance measure of blob structures in scale-space,
      where local contrast is measured either relative to a local or global reference
      level. Experiments on real brain data show that (i) the global approach with
      absolute base level has a higher degree of correspondence to a traditional
      statistical method than a local approach with relative base level, and that (ii)
      the global approach with absolute base level gives a higher significance to small
      blobs that are superimposed on larger scale structures, whereas the significance
      of isolated blobs largely remains unaffected. Relative to previously reported
      works, the following two technical improvements are also presented. (i) A post
      processing tool is introduced for merging blobs that are multiple responses to
      image structures. This simplifies automated analysis from the scale-space primal
      sketch. (ii) A new approach is introduced for scale-space normalization of the
      significance measure, by collecting reference statistics of residual noise images
      obtained from the general linear model.

PMID- 11516706
TI  - Quantitative evaluation of convolution-based methods for medical image
      interpolation.
AB  - Interpolation is required in a variety of medical image processing applications.
      Although many interpolation techniques are known from the literature, evaluations
      of these techniques for the specific task of applying geometrical transformations
      to medical images are still lacking. In this paper we present such an evaluation.
      We consider convolution-based interpolation methods and rigid transformations
      (rotations and translations). A large number of sinc-approximating kernels are
      evaluated, including piecewise polynomial kernels and a large number of windowed
      sinc kernels, with spatial supports ranging from two to ten grid intervals. In
      the evaluation we use images from a wide variety of medical image modalities. The
      results show that spline interpolation is to be preferred over all other methods,
      both for its accuracy and its relatively low computational cost.

PMID- 11516707
TI  - Interaction in the segmentation of medical images: a survey.
AB  - Segmentation of the object of interest is a difficult step in the analysis of
      digital images. Fully automatic methods sometimes fail, producing incorrect
      results and requiring the intervention of a human operator. This is often true in
      medical applications, where image segmentation is particularly difficult due to
      restrictions imposed by image acquisition, pathology and biological variation. In
      this paper we present an early review of the largely unknown territory of human
      computer interaction in image segmentation. The purpose is to identify patterns
      in the use of interaction and to develop qualitative criteria to evaluate
      interactive segmentation methods. We discuss existing interactive methods with
      respect to the following aspects: the type of information provided by the user,
      how this information affects the computational part, and the purpose of
      interaction in the segmentation process. The discussion is based on the potential
      impact of each strategy on the accuracy, repeatability and interaction
      efficiency. Among others, these are important aspects to characterise and
      understand the implications of interaction to the results generated by an
      interactive segmentation method. This survey is focused on medical imaging,
      however similar patterns are expected to hold for other applications as well.

PMID- 11516708
TI  - A global optimisation method for robust affine registration of brain images.
AB  - Registration is an important component of medical image analysis and for
      analysing large amounts of data it is desirable to have fully automatic
      registration methods. Many different automatic registration methods have been
      proposed to date, and almost all share a common mathematical framework - one of
      optimising a cost function. To date little attention has been focused on the
      optimisation method itself, even though the success of most registration methods
      hinges on the quality of this optimisation. This paper examines the assumptions
      underlying the problem of registration for brain images using inter-modal voxel
      similarity measures. It is demonstrated that the use of local optimisation
      methods together with the standard multi-resolution approach is not sufficient to
      reliably find the global minimum. To address this problem, a global optimisation
      method is proposed that is specifically tailored to this form of registration. A
      full discussion of all the necessary implementation details is included as this
      is an important part of any practical method. Furthermore, results are presented
      for inter-modal, inter-subject registration experiments that show that the
      proposed method is more reliable at finding the global minimum than several of
      the currently available registration packages in common usage.

PMID- 11516709
TI  - Symbolic description of intracerebral vessels segmented from magnetic resonance
      angiograms and evaluation by comparison with X-ray angiograms.
AB  - We describe and evaluate methods that create detailed vessel trees by linking
      vessels that have been segmented from magnetic resonance angiograms (MRA). The
      tree-definition process can automatically exclude erroneous vessel segmentations.
      The parent-child connectivity information provided by our vessel trees is
      important to both surgical planning and to guidance of endovascular procedures.
      We evaluated the branch connection accuracy of our 3D vessel trees by asking two
      neuroradiologists to evaluate 140 parent-child connections comprising seven
      vascular trees against 17 digital subtraction angiography (DSA) views. Each
      reviewer rated each connection as (1) Correct, (2) Incorrect, (3) Partially
      correct (a minor error without clinical significance), or (4) Indeterminate.
      Analysis was summarized for each evaluator by calculating 95% confidence
      intervals for both the proportion completely correct and the proportion
      clinically acceptable (completely or partially correct). In order to protect the
      overall Type I error rate, alpha-splitting was done using a top down strategy. We
      additionally evaluated segmentation completeness by examining each slice in 11
      MRA datasets in order to determine unlabeled vessels identifiable in cross
      section following segmentation. Results indicate that only one vascular parent
      child connection was judged incorrect by both reviewers. MRA segmentations
      appeared complete within MRA resolution limits. We conclude that our methods
      permit creation of detailed vascular trees from segmented 3D image data. We
      review the literature and compare other approaches to our own. We provide
      examples of clinically useful visualizations enabled by our methodology and taken
      from a visualization program now in clinical use.

PMID- 11516710
TI  - Genotoxicity studies of three triazine herbicides: in vivo studies using the
      alkaline single cell gel (SCG) assay.
AB  - Triazine herbicides are prevalent contaminants of groundwater in the agricultural
      regions of the United States. The literature on the genotoxicity of triazines is
      rife with conflicting data, though the general tendency is for most studies to
      report negative results. In order to investigate further the genotoxicity of
      triazines, we exposed mice to triazines by intraperitoneal injection up to the
      maximum tolerated doses. About 24h later, blood was removed, and the leukocytes
      subjected to DNA damage analysis using the alkaline single cell gel
      electrophoresis assay (SCG), one of the most sensitive DNA damage assays
      available. Our results indicate that atrazine induced a small dose-related
      increase in DNA damage. Simazine did not induce any dose-related increase in DNA
      damage. Cyanazine induced a marginal increase in DNA damage with dose, but no
      individual dose was significantly increased compared to the control. These
      results indicate that these triazines, even at extremely high concentrations,
      have only marginal DNA-damaging activity in vivo in mouse leukocytes.

PMID- 11516712
TI  - Evidence for DNA damage in patients with coronary artery disease.
AB  - According to the "monoclonal hypothesis" of atherosclerosis, several studies
      suggest that cancer and atherosclerosis may have several fundamental biological
      mechanisms in common. Therefore, an increase in the mutation rate may be involved
      in the pathogenesis of atherosclerotic plaques. The aim of the study was to
      verify the presence of chromosomal damage in peripheral blood lymphocytes in
      patients with coronary artery disease by using micronucleus (MN) test, a reliable
      biomarker in genetic and cancer risk assessment. Subjects included 53 patients
      with documented coronary ischemic heart disease (group I); 10 patients with
      valvular heart disease in absence of atherosclerotic lesions of the coronary
      arteries (group II) and 16 healthy subjects, age- and sex-matched (group III)
      were studied as controls. For each subject, two separate cultures were performed
      and 1000 binucleated cells were scored for the evaluation of MN frequency. The
      mean (+/-S.E.M.) of MN frequency were 11.9+/-1.7, 5.9+/-1.2 and 3.6+/-0.7 in
      groups I, II and III, respectively. The MN frequency of group I was significantly
      higher than that of group III (P=0.02). In group I, MN frequency increased with
      the number of affected vessels (6.3+/-0.7, 13.9+/-1.6, 14.9+/-5.3 for one-, two-,
      and three-vessel disease, respectively). Scheffe's test showed that MN frequency
      was significantly higher in two-vessel compared with one-vessel disease
      (P=0.0077). Moreover, a positive relationship was found between MN levels and the
      severity of the disease, calculated by the Duke scoring system (R=0.28, P=0.032),
      as well as the systolic blood pressure (R=0.34, P=0.009). These results suggest
      that coronary artery disease in humans is a condition characterized by an
      increase of DNA damage, positively correlated with the severity of the
      atherosclerotic disease.

PMID- 11516711
TI  - Characterization of O(6)-methylguanine-DNA-methyltransferase (O(6)-MGMT) activity
      in Xiphophorus fishes.
AB  - We utilized a custom-synthesized double-strand oligonucleotide containing a
      single O(6)-methylguanine (O(6)-MG) residue within a restriction endonuclease
      recognition site to determine O(6)-methylguanine-DNA-methyltransferase (O(6)
      MGMT) activity in various tissue extracts prepared from Xiphophorus fish. The
      results suggest Xiphophorus fish O(6)-MGMT activity has many of the same
      characteristics as Escherichia coli and mammalian O(6)-MGMT's including rapid
      reaction kinetics consistent with stoichiometric removal of methyl groups, but
      exhibits a temperature optimum of 23 degrees C. Results from protein extract
      activity assays indicate O(6)-MGMT activity patterns among four Xiphophorus
      tissues followed the order: brain> or =testes>gill> or =liver. In mammals, O(6)
      MGMT activity is high in liver, while activity in brain is minimal (i.e.
      approximately 9% of liver); however, we report that in the Xiphophorus fishes
      examined, brain tissue extracts exhibited much higher (approximately six-fold)
      O(6)-MGMT activity levels than liver. Comparison of O(6)-MGMT activity between
      Xiphophorus species employed in tumor induction experiments did not indicate
      significant differences in ability to clear the pre-mutagenic O(6)-MG from the
      oligonucleotide substrate.

PMID- 11516713
TI  - Cytotoxic effect of three arsenic compounds in HeLa human tumor and bacterial
      cells.
AB  - Numerous epidemiological studies suggest that arsenic (As) compounds are
      carcinogens, however, recent data have renewed the interest in their
      anticarcinogenic properties. The cytotoxic effects of three arsenic compounds
      were assessed: sodium arsenite, sodium arsenate and sodium cacodylate,
      representing the trivalent and pentavalent species of arsenic, along with a
      dimethylated pentavalent arsenic species. HeLa cells and Salmonella typhimurium
      (strains TA98 and TA100) were exposed to As compounds and the cytotoxic effects
      were evaluated. Alterations on RNA and DNA synthesis in HeLa cells were also
      examined. All arsenic compounds produced a dose-dependent inhibition on colony
      formation and DNA synthesis in HeLa cells, yet any of them significantly
      influenced RNA synthesis in these cells. No evidence of arsenic-induced
      mutagenicity or antimutagenicity was observed using the Ames assay. In bacterial
      cells, only sodium arsenite caused a dose-dependent inhibition of colony
      formation.Collectively, these results indicate that in both, HeLa and S.
      typhimurium cell systems, only trivalent sodium arsenite can act as an effective
      inhibitor of cell growth. The possible mechanism(s) of the cytotoxic effect of
      arsenite in these two different cell systems might be due to its reactivity with
      intracellular sulfhydryl groups.

PMID- 11516714
TI  - A comparison of intraperitoneal and oral gavage administration in comet assay in
      mouse eight organs.
AB  - One of the important advantages of the comet assay is its ability to detect
      genotoxicity in many different organs. Since the exposure route of the test
      compounds is likely to influence the genotoxicity detected in a given organ, it
      is an important factor to consider when conducting the assay. In this study, we
      compared the effects of numerous model compounds on eight organs when
      administered to mice by intraperitoneal (i.p.) injection and oral (p.o.) gavage.
      Groups of four mice were treated once i.p. or p.o. at the identical proportion of
      LD50 for each route, and the stomach, colon, liver, kidney, bladder, lung, brain,
      and bone marrow were sampled 3, 8, and 24h after treatment. For 19 of the 20
      tested mutagens with various modes of action, genotoxicity in some organs varied
      with treatment route; only the genotoxicity of methyl methane sulfonate was not
      affected. Treatment route, however, did not produce a qualitative difference in
      the genotoxicity of promutagens at the sites of conversion to ultimate mutagens,
      with aromatic hydrocarbons as the exception. When chemicals with positive
      responses in at least one organ were considered to be comet assay-positive, the
      administration route made no difference. Since azo reduction is mediated by azo
      reductase synthesized in the gastrointestinal wall and by gut microflora and i.p.
      administered azo dyes bypass their activation site (colon), the administration
      route is expected to make a difference in their in vivo genotoxicity. Direct
      acting mutagens are expected to affect the mucosa of the gastrointestinal tract
      when given p.o. For those mutagens, however, the administration route did not
      make a qualitative difference in gastrointestinal tract genotoxicity. Moreover,
      although the gastrointestinal mucosa is the first site to be exposed to p.o.
      administered agents, the peak times in the stomach tended to be the same as in
      most other organs. Based on those results, we concluded that the genotoxicity at
      high exposures was due to a systemic effect, and that both routes are acceptable
      for the comet assay when the liver and gastrointestinal organs are sampled, so
      long as appropriate dose levels for systemic exposure are selected for each
      route.

PMID- 11516715
TI  - ELF magnetic field affects proliferation of SPD8/V79 Chinese hamster cells but
      does not interact with intrachromosomal recombination.
AB  - Extremely low-frequency (ELF) magnetic fields have previously been shown to
      affect conformation of chromatin, cell proliferation, and calcium metabolism.
      Possible mutagenic and carcinogenic effects of ELF have also been discussed and
      tested. In this study, intrachromosomal recombination in the hprt gene after
      exposure to ELF magnetic field was investigated using the SPD8 recombination
      assay. SPD8 cells, derived from V79 Chinese hamster cells were exposed to ELF at
      a specific combination of static and ELF magnetic fields, that has been proven to
      have effects on chromatin conformation in several cell types. The genotoxic agent
      camptothecin (CPT) was used either as a positive control or simultaneously with
      ELF. We also analysed the effect of ELF and CPT on chromatin conformation with
      the anomalous viscosity time dependence (AVTD) technique, cell growth kinetics,
      and cell survival with clonogenic assay. DNA fragmentation was analysed by pulsed
      field gel electrophoresis (PFGE). ELF did not induce recombination alone, neither
      did ELF modify the recombinogenic effect of CPT. Although, there was no effect on
      cell survival in response to ELF exposure, inhibition of cell growth was
      observed. On the other hand, ELF exposure partly counteracted the growth
      inhibition seen with CPT. The data suggest that ELF exposure may stimulate or
      inhibit cell growth depending on the state of the cells. Although, ELF did not
      induce recombination, a weak but statistically significant DNA fragmentation
      comparable with CPT-induced fragmentation was observed with PFGE 48h after
      exposure to ELF.

PMID- 11516716
TI  - Accumulation of mitochondrial DNA deletions in human oral tissues -- effects of
      betel quid chewing and oral cancer.
AB  - Accumulation of mitochondrial DNA (mtDNA) mutations in human tissues has been
      associated with intrinsic aging and environmental insult. Recently, mtDNA
      mutations have been detected in various tumors, including head and neck tumors.
      However, the factors affecting the occurrence and accumulation of mtDNA deletions
      in tumor tissues are poorly understood. In Taiwan, betel quid chewing is a major
      risk factor for oral cancer. Using polymerase chain reaction (PCR) techniques, we
      examined large-scale deletions of mtDNA in 53 pairs of tumor and non-tumor oral
      tissues from the patients with or without betel quid chewing history. The results
      revealed that irrespective of the history of betel quid chewing, the incidences
      of the 4977bp deletion and other deletions of mtDNA were lower in the tumor
      portion as compared with the non-tumor portion. The average proportions of the
      4977bp deleted mtDNA in the tumor tissues of the betel quid chewers and non-betel
      quid chewers were 13- and 5-fold, respectively, lower than those in the
      corresponding non-tumor tissues. Moreover, the average proportion of 4977bp
      deleted mtDNA was significantly higher (P<0.05) in the non-tumor oral tissues of
      the patients with betel quid chewing history than that of the patients without
      the history of betel quid chewing. These results suggest that betel quid chewing
      may increase mtDNA mutation in human oral tissues and that accumulation of mtDNA
      deletions and subsequent cytoplasmic segregation of these mutations during cell
      division could be an important contributor to the early phase of oral
      carcinogenesis.

PMID- 11516717
TI  - Chromosomal effects of newly identified water pollutants PBTA-1 and PBTA-2 and
      their possible mother compounds (azo dyes) and intermediates (non-ClPBTAs) in two
      Chinese hamster cell lines.
AB  - We performed the in vitro micronucleus (MN) test on 2-[2-(acetylamino)-4-[bis(2
      methoxyethyl)amino]-5-methoxyphenyl]-5-amino-7-bromo-4-chloro-2H-benzotriazole
      (PBTA-1) and 2-[2-(acetylamino)-4-[N-(2-cyanoethyl)-ethylamino]-5-methoxyphenyl]
      5-amino-7-bromo-4-chloro-2H-benzotriazole (PBTA-2), which are newly identified
      water pollutants from the Nishitakase river in Kyoto, Japan, and on their
      possible mother compounds (AZO DYE) and intermediates (non-ClPBTAs). We tested
      these compounds in the absence and presence of S9 mix in two Chinese hamster cell
      lines CHL and V79-MZ and scored MN, polynuclear and karyorrhectic (PN), and
      mitotic (M) cells. PBTA-2 in the absence of S9 mix induced the strongest
      responses in both cell lines. It was also a strong inducer of binucleate cells in
      PN cells in both cell lines, which suggested that it induced polyploidy. PBTA-1
      showed clear positive results only in the absence of S9 mix and only in V79-MZ
      cells, inducing aneuploidy. In CHL cells AZO DYE-1 significantly induced MN cells
      in the presence of S9 mix, and AZO DYE-2 induced MN and PN cells, including
      binucleate cells and cells with a multilobed nucleus, in the absence of S9 mix.
      In V79-MZ cells, AZO DYE-1 and -2 induced primarily M cells in the presence of S9
      mix. 9% of the M cells treated with 50 microg/ml AZO DYE-1 showed
      endoreduplication. AZO DYE-2 at 200 microg/ml condensed the chromatin in 100% of
      the cells. The non-ClPBTAs were a bit more cytotoxic than the other compounds and
      induced a slight increase in MN cells in both cell lines. Some of the chemicals
      tested induced a characteristic karyomorphology that might reflect abnormal cell
      division. Abnormalities of cell division could be detected in PN and M cells as
      well as in MN cells. Structure-activity relationships have also been discussed.

PMID- 11516718
TI  - DNA damage and repair in Arabidopsis thaliana as measured by the comet assay
      after treatment with different classes of genotoxins.
AB  - The three protocols of the comet assay A/N, A/A and N/N were for the first time
      applied to the plant species Arabidopsis thaliana. The purpose of the experiments
      was to establish conditions for genotoxic exposure causing DNA damage in
      Arabidopsis nuclei. This is required for comprehensive gene expression profiling
      with the intention to screen for genes involved in response of Arabidopsis cells
      to genotoxic stress. Five chemicals belonging to different classes of mutagens
      (the monofunctional alkylating agents N-methyl-N-nitrosourea and methyl
      methanesulfonate, the polyfunctional alkylating agent mitomycin C, the
      radiomimetic bleomycin and the herbicide maleic hydrazide) were tested. Except
      for maleic hydrazide, dose-dependent increases in DNA damage were found using the
      A/N comet assay protocol. While a rapid repair of bleomycin-mediated SSBs and
      DSBs was found, no significant reduction of DNA migration was observed up to 48h
      after treatment with the monofunctional alkylating agents.

PMID- 11516719
TI  - The comet assay detects adaptation to MNU-induced DNA damage in barley.
AB  - We have established the comet assay for detection of DNA damage in barley.
      Immediately after treatment with the monofunctional alkylating agent MNU, a dose
      dependent increase of DNA damage (mainly DNA breaks) was detected by the alkaline
      denaturation/neutral gel electrophoresis (A/N) variant of the comet assay in
      nuclei isolated from root tip meristems and from young leaves. A reduction of
      damage was observed within meristematic nuclei but not in differentiated leaf
      nuclei 48h after treatment. Adaptive pretreatment with a nontoxic dose of cadmium
      chloride prior to challenge treatment with MNU reduced the frequency of chromatid
      type aberrations, micronuclei and aneuploid cells as well as the amount of DNA in
      comet tails of meristematic nuclei.

PMID- 11516720
TI  - Spindle poisons induce allelic loss in mouse lymphoma cells through mitotic non
      disjunction.
AB  - Aneuploidy is an important contributor to reproductive failure and tumor
      development. It arises spontaneously or as a result of exposure to aneugenic
      agents through non-disjunction. Two spindle poisons, colchicine (COL) and
      vinblastine (VBL) are mutagenic in the mouse lymphoma assay (MLA), a gene
      mutation assay that targets the heterozygous thymidine kinase (tk) gene on
      chromosome 11 in mouse lymphoma L5178Y tk+/- 3.7.2c cells. To investigate the
      mechanisms of spindle poison mutagenesis, we analyzed the COL- and VBL-induced TK
      mutants at the molecular and cytogenetic level. Loss of heterozygosity (LOH)
      analysis employing a microsatellite region within the tk locus revealed that
      almost all mutants had lost the functional tk allele. To determine the extent of
      the LOH, we further examined LOH mutants for heterozygosity at nine
      microsatellite loci spanning the entire chromosome 11. Interestingly, every
      microsatellite marker showed LOH in all COL- and VBL-induced LOH mutants,
      suggesting that these mutants were generated by loss of the whole chromosome 11
      through mitotic non-disjunction. Chromosome painting analysis supported this
      hypothesis; there were no mutants showing structural changes such as deletions or
      translocations involving chromosome 11. In contrast, spontaneous TK mutants
      followed from point mutations, deletions and recombinational events as well as
      whole chromosome loss. Our present study indicates that spindle poisons induce
      mutations through mitotic non-disjunction without structural DNA changes and
      supports a possible mechanism in which a recessive mutation mediated by
      aneuploidy may develop tumors.

PMID- 11516722
TI  - Induction of -2 frameshift mutations by 2-nitrofluorene, N
      hydroxyacetylaminofluorene, and N-2-acetylaminofluorene in reversion assays in
      Escherichia coli strains differing in permeability and acetyltransferase
      activity.
AB  - The mutagenicity of 2-nitrofluorene (NF), N-hydroxyacetylaminofluorene (N-OH
      AAF), and N-2-acetylaminofluorene (AAF) was measured in strains of Escherichia
      coli that contain a lacZ allele that reverts by -2 frameshift mutations from
      CG(5) to CG(4). Mutagenesis was compared in a strain having wild-type
      permeability and metabolism, a strain with increased permeability caused by a
      lipopolysaccharide-defective (LPS(d)) mutation, a strain with N- and O
      acetyltransferase (NAT/OAT) activity conferred by the Salmonella nat gene on
      plasmid pYG219, and a strain carrying both an LPS(d) mutation and pYG219. The
      LPS(d) mutation facilitated the measurement of mutagenicity but was not
      absolutely required, in that lower levels of mutagenicity were detected in LPS(+)
      strains. The NAT/OAT activity conferred by pYG219 strongly potentiated the
      mutagenicity of NF and N-OH-AAF. Surprisingly, AAF was mutagenic in the NAT/OAT
      LPS(d) strain without an exogenous P450 metabolic activation system. Its activity
      may be ascribable to the detection of a directly mutagenic impurity by the highly
      sensitive strain or to a low level of metabolic activation by the bacteria under
      the assay conditions. The findings add to the evidence that the lacZ allele
      derived from E. coli strain CC109 is an effective indicator of -2 frameshift
      mutagenesis and that strains expressing high levels of NAT/OAT activity are
      highly sensitive in monitoring the mutagenicity of nitroarenes and aromatic
      amides.

PMID- 11516721
TI  - Structures of mutagens produced by the co-mutagen norharman with o- and m
      toluidine isomers.
AB  - Norharman, abundantly present in cigarette smoke and cooked foods, is not
      mutagenic to Salmonella typhimurium strains. However, norharman shows
      mutagenicity to S. typhimurium TA98 and YG1024 in the presence of S9 mix when
      coexisting with aromatic amines, including aniline, o- and m-toluidines. We
      previously reported that the mutagenicity from norharman and aniline in the
      presence of S9 mix was due to the formation of a mutagenic compound, 9-(4'
      aminophenyl)-9H-pyrido[3,4-b]indole (aminophenylnorharman). In the present study,
      we analyzed the mutagens produced by norharman with o- or m-toluidine in the
      presence of S9 mix. When norharman and o-toluidine were reacted at 37 degrees C
      for 20 min, two mutagenic compounds, which were mutagenic with and without S9
      mix, respectively, were produced, and these were isolated by HPLC. The former
      mutagen was deduced to be 9-(4'-amino-3'-methylphenyl)-9H-pyrido[3,4-b]indole
      (amino-3'-methylphenylnorharman) on the basis of various spectral data, and this
      new heterocyclic amine was confirmed by its chemical synthesis. The latter
      mutagen was identified to be the hydroxyamino derivative. Amino-3'
      methylphenylnorharman induced 41,000 revertants of TA98, and 698,000 revertants
      of YG1024 per microg with S9 mix. Formation of the same DNA adducts was observed
      in YG1024 when amino-3'-methylphenylnorharman or a mixture of norharman plus o
      toluidine was incubated with S9 mix. These observations suggest that norharman
      reacts with o-toluidine in the presence of S9 mix to produce amino-3'
      methylphenylnorharman, and this compound is metabolically activated to yield its
      hydroxyamino derivative. After activation by O-acetyltransferase, it might bind
      to DNA and exert mutagenicity in S. typhimurium TA98 and YG1024. When norharman
      and m-toluidine were reacted in the presence of S9 mix, 9-(4'-amino-2'
      methylphenyl)-9H-pyrido[3,4-b]indole (amino-2'-methylphenylnorharman) was
      identified as a mutagen. Thus, the mutagenicity of norharman with m-toluidine may
      follow a mechanism similar to that with o-toluidine.

PMID- 11516723
TI  - Assays to predict the genotoxicity of the chromosomal mutagen etoposide --
      focussing on the best assay.
AB  - The topoisomerase II inhibitor etoposide is used routinely to treat a variety of
      cancers in patients of all ages. As a result of its extensive use in the clinic
      and its association with secondary malignancies it has become a compound of great
      interest with regard to its genotoxic activity in vivo. This paper describes a
      series of assays that were employed to determine the in vivo genotoxicity of
      etoposide in a murine model system. The alkaline comet assay detected DNA damage
      in the bone marrow mononuclear compartment over the dose range of 10--100mg/kg
      and was associated with a large and dose dependent rise in the proportion of
      cells with severely damaged DNA. In contrast, the bone marrow micronucleus assay
      was found to be sensitive to genotoxic damage between the doses of 0.1--1mg/kg
      without any corresponding increases in cytotoxicity. An increase in the mutant
      frequency was undetectable at the Hprt locus at administered doses of 1 and
      10mg/kg of etoposide, however, an increase in the mutant frequency was seen at
      the Aprt locus at these doses. We conclude that the BMMN assay is a good short
      term predictor of the clastogenicity of etoposide at doses that do not result in
      cytotoxic activity, giving an indication of potential mutagenic effects.
      Moreover, the detection of mutants at the Aprt locus gives an indication of the
      potential of etoposide to cause chromosomal mutations that may lead to secondary
      malignancy.

PMID- 11516724
TI  - Evidence for reductive activation of carcinogenic aristolochic acids by
      prostaglandin H synthase -- (32)P-postlabeling analysis of DNA adduct formation.
AB  - Aristolochic acid (AA), a naturally occurring nephrotoxin and carcinogen, is
      implicated in an unique type of renal fibrosis, designated Chinese herbs
      nephropathy (CHN), which can develop to urothelial cancer. Understanding which
      enzymes are involved in AA activation and/or detoxication is important in the
      assessment of an individual susceptibility to this natural carcinogen. We
      examined the ability of prostaglandin H synthase (PHS) to activate AA to
      metabolites forming DNA adducts with the nuclease P1 and 1-butanol extraction
      enrichment procedure of the (32)P-postlabeling assay. PHS is a prominent enzyme
      in the kidney and urothelial tissues. Ram seminal vesicle (RSV) microsomes, which
      contain high levels of PHS, generated AA-DNA adduct patterns reproducing those
      found in renal tissues in CHN patients. 7-(Deoxyadenosin-N(6)-yl)aristolactam I,
      7-(deoxyguanosin-N(2)-yl)aristolactam I and 7-(deoxyadenosin-N(6)-yl)aristolactam
      II were identified as AA-DNA adducts formed by AAI. Two adducts, 7-(deoxyguanosin
      N(2)-yl)aristolactam II and 7-(deoxyadenosin-N(6)-yl)aristolactam II, were
      generated from AAII. According to the structures of the DNA adducts identified,
      nitroreduction is the crucial pathway in the metabolic activation of AA. The
      identity of PHS as the activating enzyme in RSV microsomes was proven with
      different cofactors and inhibitors. Only indomethacin, a selective inhibitor of
      PHS, significantly decreased the amount of adducts formed by RSV microsomes. The
      inhibitor of NADPH:CYP reductase (alpha-lipoic acid) and some selective
      inhibitors of cytochromes P450 (CYP) were not effective. Likewise, only cofactors
      of PHS, arachidonic acid and hydrogen peroxide, supported the DNA adduct
      formation of AAI and AAII, while NADPH and NADH were ineffective. These results
      demonstrate a key role of PHS in the activation pathway of AAI and AAII in the
      RSV microsomal system and were corroborated with the purified enzyme, namely
      ovine PHS-1. The results presented here are the first report demonstrating a
      reductive activation of nitroaromatic compounds by PHS-1.

PMID- 11516725
TI  - p-Nonylphenol acts as a promoter in the BALB/3T3 cell transformation.
AB  - p-Nonylphenol (NP) has attracted attention as an estrogenic contaminant, and the
      environmental pollution by NP has been found to be extensive. NP is classified as
      a phenolic antioxidant based on the chemical activity and structure. Some
      phenolic antioxidants are known to induce and/or enhance carcinogenesis. We
      examined the effects of NP on the two-stage transformation of BALB/3T3 cells, a
      model of two-stage carcinogenesis. The treatment by NP in the promotion phase
      markedly enhanced the transformation of the cells pre-treated with a subthreshold
      dose of a carcinogen, 3-methylcholanthrene (MCA), but not that of non-pretreated
      cells. The promoting activity of NP was approximately one hundredth of that of 12
      O-tetradecanoylphorbol-13-acetate (TPA), a potent tumor promoter, in the cell
      transformation. The treatment by NP in the initiation phase did not induce cell
      transformation with and without post-treatment by TPA. These results indicate
      that NP acts as a pure promoter of cell transformation implying that it may cause
      the enhancement of carcinogenesis in vivo. The enhancement by NP of MCA-initiated
      transformation was suggested not to be mediated by estrogen receptors in BALB/3T3
      cells because 17 beta-estradiol did not promote cell transformation in our
      experiments, and it has been reported that BALB/3T3 cells do not express estrogen
      receptors at a detectable level.

PMID- 11516726
TI  - Relationship between correlation dimension and indices of linear analysis in both
      respiratory movement and electroencephalogram.
AB  - OBJECTIVE: We investigate the relationships between signals from the
      electroencephalogram (EEG) and those from respiratory movement using the
      correlation dimension (D(2)). METHODS: Respiratory movement and EEG were recorded
      for 7.5h from 7 clinically healthy men. D(2) was calculated by applying an
      algorithm slightly modified from that proposed by Grassberger and Procaccia (Phys
      Rev Lett 50 (1983) 346). Non-linearity in respiratory movement and EEG was tested
      by comparing D(2) for the original data with that for surrogate data. RESULTS: A
      statistically significant positive correlation between D(2) of the EEG and D(2)
      of the respiratory movement was observed for the original data, but not for the
      surrogate data. CONCLUSIONS: A reduced D(2) of the EEG may be associated with an
      increased regularity of breathing in deep sleep (stage IV). Likewise, the
      increased D(2) of respiratory movement during rapid eye movement may be
      associated with increased complexity of the signals. Whether there is a direct
      coordination between brain and lungs or whether brainstem systems, including that
      of the cholinergic system, affect both respiration and cortex requires further
      investigation.

PMID- 11516727
TI  - The effect of state on sensory gating: comparison of waking, REM and non-REM
      sleep.
AB  - OBJECTIVES: Auditory sensory gating is an electrophysiological assay that has
      been employed in clinical and basic research to clarify the neurobiological basis
      of perceptual and attentional impairments associated with schizophrenia and other
      diseases. In addition to genetically-linked characteristics, this measure also
      exhibits potentially confounding sensitivity to behavioral state, most notably
      acute stress. The goal of the present study is to determine if auditory sensory
      gating of evoked potential component P50 ('P1') could be measured during rapid
      eye movement (REM) sleep, as an alternative to the waking state. METHODS: The
      suppression of vertex-recorded auditory evoked potential components, P30, P50 and
      N100, was measured as a function of stimulus redundancy using the paired-click
      paradigm during all-night sleep in 10 control subjects. Average evoked responses
      were computed separately for 30 min periods of waking, REM sleep, and non-REM
      (stage 2) sleep. RESULTS: Evoked response component P50 exhibited suppression to
      the paired-click stimulus during REM sleep, not significantly different than
      waking. Suppression of wave N100 was significantly poorer during both sleep
      stages than waking. Component P30 was not suppressed in response to repetitive
      stimuli under any state of vigilance. CONCLUSIONS: In addition to waking,
      response suppression of evoked potential component P50 can be measured during REM
      sleep, thus allowing the separation of trait- and state-dependent effects in
      future investigations of auditory sensory gating.

PMID- 11516728
TI  - Changes of the brain electrical fields during the continuous performance test in
      attention-deficit hyperactivity disorder-boys depending on methylphenidate
      medication.
AB  - OBJECTIVE: The continuous performance test (CPT) is successfully applied to
      evaluate attentional performance in attention-deficit hyperactivity disorder
      (ADHD)-children. The aim of the present study was to investigate the changes of
      the topographic P300-features in relation to methylphenidate-medication and to
      different attentional processes in primer- and distractor-conditions. METHODS:
      Twenty-one-channel-ERPs of 17 ADHD-boys were analyzed with reference-independent
      methods. Four quasi stable microstates within the time frames of conventional
      P100, P200, P3a and P3b components were identified by means of a data-driven
      segmentation procedure. RESULTS: In segment 3 topographical assessment yielded a
      significant occipital and right-shift of the positive centroid, longer centroid
      distance and higher amplitudes in primer- than in distractor conditions. MPH
      increased the amplitude and distance in primer and distractor-condition, without
      changing the topography. In segment 4 the electric field strength of distractor
      conditions collapsed, whereas the primer condition showed a strong fronto
      parietally oriented potential-field. There was a tendency to higher amplitudes
      due to MPH-medication. CONCLUSIONS: These results indicate a robust
      neurophysiologic differentiation of cognitive processes. MPH activates an early
      (P3a) covert attention process indicated by increased amplitudes and centroid. No
      effects were seen in later processes. Based on these effects, we propose to use
      the amplitude- and distance-increase in microstate 3 as an indicator of MPH
      efficacy in ADHD-boys.

PMID- 11516729
TI  - Theta band power changes in normal and dyslexic children.
AB  - OBJECTIVE: Tonic and phasic (event-related) theta band power changes were
      analyzed in a sample of 8 dyslexic and 8 control children. Previous research with
      healthy subjects suggests that electroencephalograph (EEG) theta activity
      reflects the encoding of new information into working memory. The aim of the
      present study was to investigate whether the processing deficits of dyslexics are
      related to a reduced phasic theta response during reading. METHOD: The EEG was
      recorded while subjects were reading numbers, words and pseudowords and analyzed
      in a lower and upper theta band (4--8 Hz). A phasic response is measured in terms
      of an increase in event related band power during reading with respect to a
      reference interval. Tonic power is measured in terms of (log) band power during a
      reference interval. RESULTS: Large group differences in tonic and phasic lower
      theta were found for occipital sites where dyslexics show a complete lack of
      pseudoword processing. For words, only controls show a highly selective left
      hemispheric processing advantage. CONCLUSIONS: Dyslexics have a lack to encode
      pseudowords in visual working memory with a concomitant lack of frontal
      processing selectivity. The upper theta band shows a different pattern of results
      which can be best interpreted to reflect the effort during the encoding process.

PMID- 11516730
TI  - Alpha and beta band power changes in normal and dyslexic children.
AB  - OBJECTIVE: Previous research with healthy subjects suggests that the lower alpha
      band reflects attentional whereas the upper alpha band semantic processes. The
      aim of the present study was to investigate whether dyslexics show deficits in
      attentional control and/or semantic encoding. METHOD: The EEG was recorded while
      subjects were reading numbers, words and pseudowords and analyzed in a lower and
      upper alpha and two beta bands (spanning a range of about 8--16 Hz). A phasic
      response is measured in terms of a decrease in event related band power during
      reading with respect to a reference interval. Tonic power is measured in terms of
      (log) band power during a reference interval. RESULTS: In the lower alpha band
      dyslexics show an increased phasic response to words and pseudowords at right
      hemispheric sites but a lack to respond to words at O1. The upper alpha band
      exhibits a highly selective phasic response to words at left frontal sites but
      for controls only, whereas dyslexics show a general increase in tonic upper alpha
      power. Whereas the low frequency beta band (beta-1a) exhibits a rather diffuse
      pattern, a highly selective finding was obtained for the beta-1b band.
      CONCLUSIONS: Dyslexics have a lack of attentional control during the encoding of
      words at left occipital sites and a lack of a selective topographic activation
      pattern during the semantic encoding of words. Because only in controls reading
      of words is associated with a strong beta-1b desynchronization at those recording
      sites which correspond to Broca's area (FC5) and the angular gyrus (CP5, P3), we
      may conclude that this frequency band reflects the graphemicphonetic encoding of
      words.

PMID- 11516731
TI  - Simultaneous EEG and functional MRI of epileptic activity: a case report.
AB  - OBJECTIVES: Attempts to localize the source of epileptic activity by linking
      electroencephalographic (EEG) abnormalities to blood oxygenation level-dependent
      (BOLD) magnetic resonance imaging (MRI) signal alterations are hampered mainly by
      EEG distortions during MRI, subject motion, and unknown hemodynamic response
      characteristics. METHODS: Using T2*-weighted echo-planar imaging at 2.0 T (2 s
      temporal resolution, 2 x 2 x 4 mm(3) spatial resolution), this work demonstrates
      strategies to alleviate some of these problems while studying a patient who had
      ideopathic generalized epilepsy with poly-spike and slow-wave complexes. RESULTS:
      Continuous EEG recordings during dynamic MRI (500 ms scanning, 1500 ms delay) and
      post-examination derivation of an EEG reference function for MRI analysis
      revealed positive BOLD MRI responses with temporal characteristics similar to
      those obtained for functional challenges. CONCLUSIONS: The ability to map focal
      epileptic activity and/or associated cognitive processing provides new potential
      for both epilepsy research and clinical patient management.

PMID- 11516732
TI  - Interpretation of interdependencies in epileptic signals using a macroscopic
      physiological model of the EEG.
AB  - This paper presents a neurophysiologically relevant model in which vectorial
      epileptiform electroencephalographic (EEG) signals are produced from multiple
      coupled neural populations. This model is used to evaluate the performances of
      non-linear regression analysis as a method to characterize couplings between
      neural populations from EEG signals they produce. Two quantities, estimated on
      generated signals, namely the non-linear correlation coefficient and the
      direction index, are related to the degree and direction of coupling parameters
      of the model. Their statistical behavior is first studied on a set of signals
      simulated for relevant configurations of the model. They are then measured on
      real stereoelectroencephalographic (SEEG) signals. Results obtained in three
      patients suffering from temporal lobe epilepsy (TLE) show that abnormal
      functional couplings between cerebral structures, that establish during seizures,
      can be interpreted in terms of causality. Perspectives are oriented to the
      identification of epileptogenic networks in TLE.

PMID- 11516733
TI  - Gamma band activity in an auditory oddball paradigm studied with the wavelet
      transform.
AB  - OBJECTIVES: To examine the characteristics of evoked and induced gamma band
      oscillatory responses occurring during P300 development in an auditory oddball
      paradigm. METHODS: A time-frequency analysis method was applied to an auditory
      oddball paradigm in 7 healthy subjects. This method combines a multiresolution
      wavelet algorithm for signal extraction and the Gabor transform to represent the
      temporal evolution of the selected frequency components. Phase-locked or evoked
      activity and also non-phase-locked activity were computed for both standard and
      target stimuli. RESULTS: The gamma band frequency components differed between
      target and non-target stimuli processing. The study showed an early and mainly
      phase-locked oscillatory response appearing around 26--28 ms after both standard
      and target stimuli onset. This response showed a spectral peak around 44 Hz for
      both stimuli. A late oscillatory activity peaking at 37 Hz with a latency around
      360 ms was observed appearing only for target stimuli. The latency of this late
      oscillatory activity had a high correlation (P=0.002) to the latency of the P300
      wave. CONCLUSIONS: EEG signal analysis with wavelet transform allows the
      identification of an early oscillatory cortical response in the gamma frequency
      range, as well as a late P300-related response.

PMID- 11516734
TI  - Waveform of sympathetic skin response in diabetic patients.
AB  - OBJECTIVE: The aim of this study was to investigate whether there were
      differences in amplitude and latency among the different waveform patterns of
      sympathetic skin response (SSR) in diabetic patients. The authors also
      investigated whether the proportion of the SSR waveform patterns was influenced
      by diabetic polyneuropathy (DP), symptoms of dysautonomia, and impaired R-R
      interval variation of the heart rate. DESIGN/METHODS: Twenty SSRs from palm skin
      were analyzed in 53 diabetic patients and 45 normal subjects. Waveforms were
      classified as either the P type, in which the positive component was larger than
      the negative one, or the N type, in which the negative component was larger than
      the positive one. The patterns of occurrence in these two waveform types were
      classified into 3 kinds, i.e. P, N, and M patterns. In the P and N patterns, all
      the SSRs were of the P and N types, respectively. The M pattern had both P and N
      types during consecutive recordings. RESULTS: The patients' age and glycosylated
      hemoglobin values did not differ among the 3 SSR patterns. The P pattern,
      however, had a larger amplitude and shorter latency than the N pattern, just as
      previously reported in a normal population. The distribution of the SSR patterns
      in diabetic patients was not statistically different from that in the normal
      controls, and it was not influenced by the DP, symptoms of dysautonomia, or
      impaired R-R interval variation of the heart rate. CONCLUSIONS: The distribution
      of the SSR waveform patterns was not influenced by the pathological conditions
      related to diabetes. It might be advised to confirm the balanced distribution of
      the SSR waveform patterns in patient and control groups before comparing the
      values of amplitude and latency between the two groups.

PMID- 11516735
TI  - Clinical and neurophysiological outcome of surgery in extreme carpal tunnel
      syndrome.
AB  - INTRODUCTION: Surgical release is the most effective therapy for the symptoms of
      carpal tunnel syndrome (CTS). It is widely considered that surgery may be
      ineffective in 'extreme' cases (those with atrophy of the thenar eminence muscles
      and no sensory and motor response of the median nerve). OBJECTIVE: To report
      clinical and electrophysiological outcome of 10 subjects with 'extreme' CTS
      surgically treated. METHODS: Ten hands belonging to 10 patients (9 women and one
      man, mean age 65 years) underwent surgical release by the mini-incision of the
      palm technique. All showed atrophy of thenar eminence and absence of motor and
      sensory responses of the median nerve. The protocol consisted of clinical and
      electrophysiological evaluation, with the patient completing the self
      administered Boston questionnaire (BQ) before the operation and one and 6 months
      after it. RESULTS: After surgical release, all patients reported an absence of
      pain and disappearance or reduction of paraesthesia. Six months after the
      operation, motor and sensory responses of the median nerve returned in 8 and 5
      hands, respectively. The BQ showed a significant improvement in symptom and
      functional scores, although muscle atrophy remained unchanged. No correlation was
      found between the degree of clinical and electrical improvement and the age of
      the patients. CONCLUSION: It is possible to obtain good clinical and
      electrophysiological results even in extreme cases of CTS.

PMID- 11516736
TI  - Synchronization of single motor units during voluntary contractions in the upper
      and lower extremities.
AB  - OBJECTIVE: To investigate motor unit synchronization in the time and frequency
      domains and compare the amount and nature of this synchronization between upper
      and lower extremity muscles in human subjects. METHODS: A total of 120 motor unit
      pairs from biceps brachii (BB), first dorsal interosseous (1DI), vastus medialis
      (VM), and tibialis anterior (TA) on the dominant side were analyzed and compared.
      Pairs of motor unit spike trains were recorded from two concentric needle
      electrodes inserted within these muscles in healthy volunteers. Subjects were
      instructed to maintain a weak isometric contraction of these muscles so that an
      individual motor unit recorded from each concentric needle discharged at a steady
      rate of approximately 10 impulses/s. Pairs of motor unit spike trains were cross
      correlated in the time domain, and coherence analysis in the frequency domain was
      performed on the same spike train data. RESULTS: Synchronization was seen in all
      the muscles studied. Strength of motor unit synchronization, expressed as
      synchronization index (SI), was greater in 1DI muscles compared to other muscles
      (P<0.01). Coherence analysis revealed significant association between motor unit
      firings in the 1--5 and 25--30 Hz frequency ranges in all the muscles studied.
      The incidence of 25--30 Hz coherence peaks were found to be greater for 1DI
      muscles compared to other muscles. CONCLUSION: The above results suggest a
      possible role for corticospinal projections in producing pre-synaptic inputs
      responsible for synchronization of motor unit firings and 25--30 Hz coherence
      peaks.

PMID- 11516737
TI  - Anticipatory postural adjustments during load catching by standing subjects.
AB  - OBJECTIVES: (1) To study differences in the generation of anticipatory postural
      adjustments (APAs) in arm and trunk/leg muscles prior to catching a load released
      either by the subject him-/herself or by the experimenter. (2) To study the
      importance of different mechanical characteristics of the load at impact for the
      generation of APAs prior to load catching. METHODS: Standing subjects were asked
      to catch loads dropped onto the left hand from different heights either by the
      experimenter or by the subject's right hand. The load mass and release height
      were manipulated to keep either the mass or the momentum of the load at impact
      constant. APAs were quantified with integral electromyographic indices. RESULTS:
      APAs were observed in leg, trunk and arm muscles prior to load impact for both
      self- and experimenter-release trials. Kinetic energy showed higher correlations
      with the magnitude of APA than momentum, but only in experimenter-release trials.
      CONCLUSIONS: Subjects can generate APAs in both arm and trunk/leg muscles in the
      absence of an explicit voluntary action. The relative importance of kinetic
      energy and momentum for defining the magnitude of APAs can reflect the difference
      in the sources of information used to prepare for the forthcoming perturbation
      during self- and experimenter-released load catch.

PMID- 11516738
TI  - Different responses to auditory and somaesthetic stimulation in patients with an
      excessive startle: a report of pediatric experience.
AB  - OBJECTIVES: Children with cerebral injury often exhibit brief muscle contraction
      to a variety of stimuli. However, it remains to be determined whether or not the
      pattern of the reaction is stereotypical irrespective of the site stimulated. To
      answer this question, we studied electromyographic (EMG) responses to three types
      of stimuli in children. METHODS: The EMG responses of cranial and limb muscles
      were recorded after acoustic or somaesthetic stimulation in 6 patients and 23
      control subjects. RESULTS: Acoustic stimuli evoked patterned motor activity with
      a rostrocaudal progression. Nose-tapping stimuli elicited reflex EMG activity in
      the VIIth cranial muscles that was similar to the R1 component of the electrical
      blink reflex. Sternum-tap stimuli evoked motor activity in the
      sternocleidomastoid and arm muscles, and this reflex was probably mediated
      through the cervical cord (H-reflex). Moreover, late reflexes were evoked
      following these early reflexes in the patients. In particular, atypical forms of
      myoclonic jerks were evoked on sternum-tap stimuli. CONCLUSIONS: Many types of
      primitive reflexes were evoked following three types of stimuli. These reflexes
      included startle reflex, trigeminomotor reflex, H-reflex and atypical forms of
      myoclonus, and they were enhanced in the patient group. There are many startle
      mimicking reflexes.

PMID- 11516739
TI  - Regulation of motor output between young and elderly subjects.
AB  - OBJECTIVES: Considerable information exists concerning the differences in
      motoneuron pool (MP) excitability between young and elderly subjects. A recent
      study demonstrated decreased heteronymous Ia facilitation with aging, suggesting
      increased presynaptic inhibition (PI) with increasing age as a mechanism for this
      change (Morita et al., Exp Brain Res 104 (1995) 167). It has been suggested that
      during voluntary movement, supraspinal, and possibly, segmental mechanisms
      (Hultborn et al., J Physiol 389 (1987) 757) modulate this inhibition. It is
      theorized that PI can modulate the recruitment gain of the MP during movement
      without altering the excitability of the motoneurons. Therefore, the purpose of
      this study was to examine the roles of PI and volitional volleys in modulating MP
      output in young and elderly subjects. METHODS: Twenty apparently healthy females
      participated in this study, 10 college aged (mean age, 22.4+/-2.8 years) and 10
      independent, community dwelling elderly (mean age, 77.6+/-5.4 years). All
      subjects were tested in a semi-recumbent position. H-reflexes were elicited at
      rest, and at 10 and 20% of maximal voluntary contraction. To assess MP output,
      background electromyography (EMG) was monitored prior to stimulation. The
      stimulus intensity was adjusted during volitional contractions to ensure similar
      control reflexes (25% of the maximal motor response (M-max)) at each level of
      contraction. RESULTS: Control reflexes at each level of volitional contraction
      (rest, 10 and 20%) were similar for both groups. To assess PI and to estimate the
      extent to which a change in the H-reflex amplitude reflects a change in MP
      gating, the common peroneal nerve was stimulated at 1.5 times the motor threshold
      100 ms prior to stimulation of the tibial nerve. Significantly greater PI was
      observed for the young subjects at rest (5 vs. 13% M-max). At both 10 and 20%
      levels of voluntary contraction, the conditioned reflex was significantly
      different from rest for the young subjects. The elderly subjects, in contrast,
      failed to modulate the conditioned reflex until the 20% of maximal voluntary
      contraction (MVC) condition. When examining the recruitment gain in the MP during
      the PI condition (H-reflex amplitude as a function of EMG levels), a significant
      group effect was observed, with the young subjects demonstrating significantly
      higher PI gain. CONCLUSIONS: These results indicate differential control of MP
      output (e.g. PI vs. volitional volleys) in young and elderly subjects.

PMID- 11516740
TI  - Time-on-task analysis using wavelet networks in an event-related potential study
      on attention-deficit hyperactivity disorder.
AB  - OBJECTIVE: The aim of this event-related potential (ERP) study was to test time
      on-task analysis at the level of single sweeps in a clinical trial. Since
      inattentiveness is one of the main symptoms of attention-deficit hyperactivity
      disorder (ADHD), this child psychiatric disorder was chosen as an exemplary
      application. METHODS: Twenty-four healthy and 24 ADHD boys, aged 9--15 years,
      performed an auditory selective attention task for about 5 min. ERP single trials
      were analyzed using wavelet networks. Time-on-task analysis was applied to
      omission errors, reaction time and slow ERP components (frontal negativity,
      parietal positivity), represented by a low-frequency wavelet component. RESULTS:
      Both performance and ERP measures showed distinct temporal dynamics. Time-on-task
      effects were not only linear, but also of higher order and started after less
      than 1 min. For ADHD children, earlier time-on-task effects, i.e. an earlier
      increase of omission errors and frontal negativity, resulted. Healthy children
      could allocate more attentional resources during the course of the experiment.
      CONCLUSION: Time-on-task analysis at the level of single trials revealed
      phenomena probably reflecting ADHD children's attentional deficits. Thus, a more
      differentiated ERP analysis may provide a better understanding of the
      pathophysiological background in neuropsychiatric disorders.

PMID- 11516741
TI  - Detection of non-linearity in the EEG of schizophrenic patients.
AB  - OBJECTIVE: The aim of this study is to detect non-linearity in the EEG of
      schizophrenia with a modified method of surrogate data. We also want to identify
      if dimension complexity (correlation dimension using spatial embedding) could be
      used as a discriminating statistic to demonstrate non-linearity in the EEG. The
      difference between the attractor dimension of healthy subjects and schizophrenic
      subjects is expected to be interpreted as reflecting some mechanisms underlying
      brain wave by views of non-linear dynamics analysis may reflect mechanistic
      differences. METHODS: EEGs were recorded with 14 electrodes in 18 healthy male
      subjects (average age: 26.3; range: 20--35) and 18 male schizophrenic patients
      (average age: 30.6; range: 24--40) during a resting eye-closed state. Neither of
      two groups was taking medicines. All artificial epochs in the EEG records were
      rejected by an experienced doctor's visual inspection. RESULTS: Testing non
      linearity with modified surrogate data, we showed that correlation dimension of
      EEG data of schizophrenia does refuse the null hypothesis that the data were
      resulted from a linear dynamic system. A decrease of dimension complexity was
      found in the EEG of schizophrenia compared with controls. We interpreted it as
      the result of the psychopath's dysfunction overall brain. The surrogating
      procedure results in a significant increase in D(s). CONCLUSIONS: Non-linearity
      of the EEG in schizophrenia was proven in our study. We think the correlation
      dimension with spatial embedding as a good discriminating statistic for testing
      such non-linearity. Moreover, schizophrenic patients' EEGs were compared with
      controls and a lower dimension complexity was found. The results of our study
      indicate the possibility of using the methods of non-linear time series analysis
      to identify the EEGs of schizophrenic patients.

PMID- 11516742
TI  - Regulating action: alternating activation of midline frontal and motor cortical
      networks.
AB  - OBJECTIVES: Focal electrical fields recorded over the midline prefrontal cortex
      have been found to index rapid evaluative decisions, including the recognition of
      having made an error in a speeded response task. The nature of these electrical
      fields and how they are related to cortical areas involved in response execution
      remains to be clarified. METHODS: As subjects performed a speeded response task
      the EEG was recorded with a 128-channel sensor array. By filtering out the large
      slow waves of the event-related potential, we found that the error-related
      negativity (Ne/ERN) arises from a midline frontal oscillation that alternates
      with oscillations over lateral sensorimotor cortex. Electrical source analyses
      were used to determine the brain sources involved in the generation of these
      oscillations. RESULTS: The results show that the midline and lateral oscillations
      have a period of about 200 ms (theta), and they are present for both correct and
      error responses. When an error is made, the midline error oscillation is
      recruited strongly, and it becomes correlated with the motor oscillation. Source
      analyses localized the midline error oscillation to centromedial frontal cortex
      and the lateral oscillation to sensorimotor cortices. CONCLUSIONS: Because of the
      similarity between the midline oscillation observed in the present study and
      frontal midline theta, the nature of the Ne/ERN may be clarified by the frontal
      midline theta literature. The correlation between the midline and sensorimotor
      oscillations suggests a possible mechanism for how midline frontal evaluative and
      monitoring networks contribute to action regulation.

PMID- 11516743
TI  - Uncoupling of contingent negative variation and alpha band event-related
      desynchronization in a go/no-go task.
AB  - OBJECTIVES: To examine how the differences in the sequences of brain activation
      during the go/no-go delayed response choice reaction time (RT) task are reflected
      into two concurrent methods of measuring brain electrical activity, the alpha
      band event-related desynchronization (alpha ERD) and the contingent negative
      variation (CNV). METHODS: alpha ERD and CNV were calculated using appropriate
      techniques from the same samples of electroencephalographic activity recorded
      during performance of a cued choice go/no-go delayed response RT task (i.e. S1
      (go/no-go)--S2 paradigm) in 8 healthy subjects. RESULTS: All segments of the CNV
      traces were different in the go and the no-go conditions. The go CNV traces
      displayed a typical pattern of slow rising negativity reflecting the build-up of
      attentional resources necessary for adequate performance of the task. On the
      other hand, the no-go traces remained close to zero reflecting the 'withdrawal'
      of further preparation after evaluation of S1. During the same period, both go
      and no-go ERD traces showed a gradual decrease in alpha band power
      (desynchronization) that was evident until shortly before the presentation of S2.
      It was only in the 500 ms before S2 presentation that there was any indication
      that the go and no-go ERD traces were different, but this did not reach
      statistical significance. CONCLUSIONS: Our data show that the pattern of the
      go/no-go difference in alpha ERD traces does not correspond to the pattern that
      can be seen in the CNV traces. This suggests that there is no direct coupling of
      CNV and alpha ERD, most probably because they measure different aspects of
      cortical electrical activity. In addition, the extent of the no-go alpha ERD
      reveals that refraining from performance of a pre-programmed movement is by no
      means a passive/inactive process.

PMID- 11516744
TI  - Multiplicity in the high-frequency signals during the short-latency somatosensory
      evoked cortical activity in humans.
AB  - OBJECTIVE: Recent studies using electroencephalography or magnetoencephalography
      have shown that peripheral nerve stimulations produce short-latency high
      frequency signals in the human somatosensory cortex. The present study tested
      whether they consist of more than one distinct type of signal. METHODS: Somatic
      evoked magnetic fields (SEFs) elicited by electrical stimulation of the median
      nerve were measured in 12 healthy volunteers. They were analyzed using a time
      frequency analysis method based on Gabor filters and another based on
      autoregressive moving average, and also with bispectrum and bicoherence
      techniques and a new dispersion curve method. RESULTS: Signals in two separate
      high-frequency bands (200 and 600 Hz) were distinguished from the main signal in
      the low frequency (LF) range during the time period of N20m and P25m. The novel
      200 Hz-band signal was seen reliably in those channels where the LF band signal
      was weak, so that the former was not masked by the latter. The 600 Hz signal
      consisted of two distinct components or parts (p1 and p2) in 10 out of 12
      subjects, one peaking during ascending slope and the second during the descending
      slope of the N20m. The latency of the p1 was shorter than the latencies of the
      200 Hz and LF signals according to the dispersion curve analysis. The inter-peak
      interval of p1 became shorter for later peaks in all 12 subjects. Bicoherence
      analysis revealed a significant phase coupling between the 200 and 600 Hz bands.
      CONCLUSIONS: There are three distinct types of signal during the time period of
      the short-latency cortical components of the SEF -- LF which gives rise to the
      commonly seen waveform of the SEF, the newly found 200 Hz signal and the 600 Hz
      signal which consists of two components. The possible origins of the high
      frequency signals are discussed in light of the new set of evidence found in the
      present study.

PMID- 11516745
TI  - The temporal profile of interactions between sensory information from both hands
      in the secondary somatosensory cortex.
AB  - OBJECTIVE: To elucidate the temporal profile of interactions between sensory
      information from both hands in the somatosensory cortex. METHODS: Somatosensory
      evoked fields (SEFs), generated by stimulation applied to the right index finger
      after a preceding stimulation to the left index finger, were recorded using a
      whole head-type magnetoencephalography (MEG). The paired electrical stimuli were
      applied with a stimulation onset asynchrony (SOA) of 50, 100, 200, 300, or 400
      ms. RESULTS: The mean SEF intensities in the primary somatosensory area (SI) of
      five subjects, which were evoked approximately 40 ms after the latter of the
      paired stimuli, were not significantly smaller than that evoked in the control
      condition when only the right finger was stimulated. In contrast, SEFs in the
      secondary somatosensory area (SII), generated approximately 100 ms after the
      stimuli, were suppressed when the paired stimuli were applied at an SOA of 100 ms
      (P<0.05, t test). In addition, SEFs at approximately 150 ms after the stimuli
      were significantly suppressed at SOAs of 50, 100 (P<0.05), 200, and 300 ms
      (P<0.1). CONCLUSION: Within a time window of approximately 300 ms, sensory
      information from the left finger significantly affected the SEFs generated by
      sensory inputs from the right finger. This time window may be required for the
      integration of sensory input.

PMID- 11516746
TI  - Two evoked responses with different recovery functions in the primary
      somatosensory cortex in humans.
AB  - OBJECTIVES: We investigated the recovery function of somatosensory evoked
      magnetic cortical fields (SEFs) to confirm the temporal aspects of the
      somatosensory process in humans. METHODS: SEFs were recorded following median
      nerve electrical stimulation in 6 healthy subjects. Double stimulation, with
      interstimulus intervals (ISIs) from 3 to 100 ms, was applied, and the SEF
      components for the second stimulation were analyzed. In a supplementary
      experiment, responses to single stimulations of various intensities from the
      sensory threshold to the motor threshold were studied. RESULTS: The first SEF
      component (1M) diminished when the ISI was less than 10 ms, while the second
      component (2M) remained even when the ISI was 3 ms. The two components showed a
      very similar attenuation with decrease of stimulus intensity. There was no
      significant difference in dipole location between 1M and 2M in the primary
      somatosensory cortex (SI). CONCLUSIONS: The results suggested that at least two
      independent pathways with different recovery functions exist in a similar area in
      the SI.

PMID- 11516747
TI  - Changes in the retinocortical evoked potentials in subjects 75 years of age and
      older.
AB  - OBJECTIVE: Current trends are showing a rapid increase in the elderly population,
      particularly the subgroup that is 75 years of age or more. Considering the fact
      that several ocular diseases are more prevalent among the elderly, it is
      increasingly important to investigate normal visual function in this subgroup of
      our population. The objective of this study was to determine the effects of
      advanced aging on visual retinocortical function by evaluating the
      electrophysiological responses of the most rapidly increasing segment of the
      geriatric population. METHODS: Fifty-eight healthy subjects between the ages of
      20--32 years (n=30) and 75--88 years (n=28) participated in this study. We
      recorded their pattern electroretinograms (ERGs) and cortical visual evoked
      potentials (VEPs) under stimulus conditions biased toward the preferential
      response of the magnocellular and parvocellular subdivisions of the visual
      system. RESULTS: Elderly subjects showed reduced ERG amplitudes relative to young
      participants. The amplitude of the VEPs also decreased with age, while their
      latency increased. The effect of senescence was most apparent under stimulus
      conditions combining the magnocellular and parvocellular pathway contributions
      and less pronounced when the stimulus conditions were biased to favor the
      response of either system. CONCLUSIONS: Our results demonstrate that visual
      retinal and cortical function deteriorates with old age. Our data further
      indicate that senescence has widespread effects on the visual system, altering
      the functioning of both the magnocellular and parvocellular visual pathways.

PMID- 11516748
TI  - Electrophysiological estimate of human cortical magnification.
AB  - OBJECTIVE: The cortical magnification factor characterizes the area of human
      primary visual cortex activated by a stimulus as a function of angular distance
      from an observer's line of sight. This study estimates human cortical
      magnification using an electrophysiological method with excellent temporal
      resolution: visual evoked potential (VEP) dipole source localization. METHODS:
      For each of 60 independently modulated checkerboard patches within the central 18
      deg of the visual field, location, orientation, magnitude, and time-course of the
      dipole current source that best described the VEP distribution across a multi
      electrode array was obtained. At numerous eccentricities, cortical magnification
      was determined using two different techniques: (1) the distance between each pair
      of adjacent stimulus patches was matched to the corresponding distance between
      adjacent cortical sources; and (2) the area of each stimulus patch was matched to
      the magnitude of the corresponding cortical source (which was assumed to be
      proportional to cortical area). RESULTS: The estimates of human cortical
      magnification using our electrophysiological method were similar to previous
      estimates from psychophysics, cortical stimulation, and functional magnetic
      resonance imaging. CONCLUSIONS: The concordance of results provided by these
      disparate technologies, with differing spatial and temporal limitations, supports
      their combination in studying the spatio-temporal dynamics of human brain
      function.

PMID- 11516749
TI  - Changes in electrovestibular brainstem responses after aminoglycoside
      intoxication in guinea pigs.
AB  - OBJECTIVE: To verify the usefulness of short-latency vestibular responses evoked
      by a combination of round window electrical stimulation and sinusoidal rotation
      (electrovestibular brainstem responses; EVBRs) as a new monitoring tool of the
      vestibular function in animal experiments. METHODS: EVBRs were obtained before,
      during, and after treatment with aminoglycosides, along with compound action
      potential (CAP) audiograms. The changes in EVBRs were compared with morphological
      changes observed by scanning electron microscopy. RESULTS: EVBR amplitudes did
      not change in the group of guinea pigs treated with amikacin, but markedly
      decreased in the streptomycin and gentamicin- treated groups. CAP audiograms
      indicated a significant threshold elevation in the amikacin group, a moderate
      elevation in the gentamicin group, and no change in the streptomycin group. Under
      scanning electron microscopy, the loss of the sensory hair cells observed in the
      cristae ampullares was slight to moderate in the amikacin group, moderate to
      severe in the streptomycin group, and severe in the gentamicin group. CONCLUSION:
      EVBRs reflect overall pathological changes undergone by vestibular hair cells,
      and support the vestibular specificity of EVBRs.

PMID- 11516750
TI  - Measuring plasma exudation in nasal lavage fluid and in induced sputum as a tool
      for studying respiratory tract inflammation.
AB  - We performed nasal lavage (NAL) combined with induced sputum to determine
      exudative inflammation in the upper and lower airways in patients with chronic
      sinusitis and in controls. To monitor plasma exudation into the respiratory lumen
      and loss of size-selectivity of the mucosa, we determined the sample-to-serum
      ratio of albumin and alpha-2-macroglobulin, Qa1b and Qa2m, and the dilution
      independent Relative Coefficient of Excretion, RCE=Qa2m/Qa1b. To detect low
      protein levels in NAL and induced sputum we adapted an ELISA system for alpha-2
      macroglobulin described by Out et al. [Clin. Chim. Acta, 165 (1987) 277-288], and
      modified this into a sensitive ELISA for albumin. Dithiothreitol, added to
      increase sputum solubility, did not interfere with the analysis, nor did N
      ethylmaleimide, added to block dithiothreitol. In this study plasma exudation in
      induced sputum is significantly increased in patients with chronic sinusitis,
      compared to controls. Plasma exudation in NAL is also increased in patients,
      although not significant. The RCE in NAL and sputum is well-correlated in one of
      the three study visits. There is much variation in sample protein-levels partly
      due to differences in dilution and the heterogeneity of the studied population.
      Determination of plasma exudation together with RCE in NAL and induced sputum is
      a good, non-invasive way to quantify inflammation of airway mucosa.

PMID- 11516751
TI  - Immunomagnetic separation methods for the isolation of Campylobacter jejuni from
      ground poultry meats.
AB  - Campylobacter jejuni is now recognized as a leading foodborne pathogen, for which
      poultry products constitute the main transmission route. Two alternative
      immunomagnetic beads (IMB) were tested for direct detection of C. jejuni ATCC
      35918 in artificially inoculated ground poultry meats and culture suspension.
      Polyclonal anti-Campylobacter antibodies were used to coat tosylactivated
      Dynabeads. The same antibodies conjugated with biotin were used to label
      streptavidin-coated beads. After these beads were incubated with inoculated
      poultry slurry or culture suspension, Campylobacter-bead complexes were separated
      from other components with a magnet. The capture efficiency was tested by plating
      bead-captured cells and unbound cells in the supernatant onto Karmali agar. The
      effects of different coating procedures, incubation time (60, 90, 120 min),
      numbers of immunomagnetic beads (10(6) to 10(7)/ml) and innoculum levels (10(3)
      to 10(7) CFU/g or ml) were determined. Without pre-enrichment, this approach
      could detect 10(4) CFU/g of ground poultry meats. These methods represent a new
      approach to extracting, concentrating and isolating Campylobacter spp. directly
      from foods.

PMID- 11516752
TI  - Multiple intestinal 'loops' provide an in vivo model to analyse multiple mucosal
      immune responses.
AB  - Mucosal immunity plays an important role in preventing disease but the induction
      of protective mucosal immune responses remains a significant challenge. We
      describe a novel in vivo model to analyze the induction of multiple mucosal
      immune responses in the small intestine. A sterile segment of intestine
      ('intestinal-segment'; 2-3 m long) was surgically prepared in the jejunum of 4-6
      month-old lambs. This 'intestinal-segment' was then subdivided into consecutive
      segments, designated as 'loops' (15-20 cm long), that included a Peyer's patch
      (PP), or 'interspaces' (15-70 cm long), that lacked a visible PP. All 'loops'
      were sterile when collected 1-4 weeks post-surgery and there was no macroscopic
      or histological evidence of altered lymph or blood flow. Flow cytometric analysis
      of cells isolated from PP, mucosal epithelium (IEL) and the lamina propria (LPL)
      revealed no significant alterations in the cell populations present in 'loop'
      tissues. The functional integrity of M-cell antigen uptake in sterile intestinal
      'loops' was evaluated by comparing the immune response induced by varying doses
      of soluble versus particulate porcine serum albumin (PSA formulated in alginate
      microspheres). A dose-dependent, PSA-specific antibody-secreting cell response
      was restricted to PP present in 'loops' injected with particulate PSA. These
      observations suggested that PP present in sterile 'loops' were functional and
      this conclusion was confirmed by detecting cholera toxin-specific antibody
      secreting cells and secreted antibody in PP and intestinal contents,
      respectively, of immunized 'loops.' Thus, each 'loop' provided an independent
      site to analyze antigen-uptake and the induction of mucosal immune responses by a
      variety of antigen or vaccine formulations.

PMID- 11516753
TI  - Simultaneous analysis of surface marker expression and cell cycle progression in
      human peripheral blood mononuclear cells.
AB  - One method for examining cell cycle kinetics by flow cytometry uses continuous
      DNA labeling with bromodeoxyuridine (BrdU), a thymidine analogue. Upon
      incorporation into DNA, BrdU causes stoichiometric quenching of the DNA
      fluorochrome Hoechst 33258. After counterstaining with a secondary DNA
      fluorochrome (e.g., ethidium bromide), the analyst can distinguish cells in
      different phases of the cell cycle over a number of mitotic cycles with flow
      cytometry. In this report, we describe a modification of the flow cytometric BrdU
      Hoechst assay that allows combined analysis of cell proliferation and
      immunophenotyping at the single cell level. To demonstrate an application of this
      method, human peripheral blood mononuclear cells were stimulated with tetanus
      toxoid or interleukin-2 for up to 6 days in the presence of BrdU, harvested, and
      immunostained for the cell surface markers CD3, CD4, CD8, CD14, CD19, and the
      cytokine receptor, CCR5. We used four-color flow cytometry analyses to
      simultaneously measure cell proliferation and surface marker expression, for the
      purpose of immunophenotyping and identifying specific cell subsets responding to
      antigen stimulation. Our successful application of this method suggests that it
      may be used to study immune responses at the molecular and cellular level and to
      identify mechanisms of immune system modulation.

PMID- 11516754
TI  - A routine assay for the direct analysis of HLA-DR-related shared epitope and B27
      alleles in chronic inflammatory arthritis.
AB  - Knowledge of the genetic background of patients with inflammatory arthritis may
      be useful for disease management. The main markers are the HLA-DR-associated
      Shared Epitope (SE) for Rheumatoid Arthritis (RA) and HLA-B27 for ankylosing
      spondylitis. We have developed a simple molecular biology-based test to provide
      this essential information. HLA targets are amplified by polymerase chain
      reaction (PCR), then simultaneously analyzed using 16 individual hybridization
      reactions in two 8-well ELISA strips with colorimetric detection. Concordance was
      evaluated using a cohort of RA patients with known genotype. Using this new
      assay, 100% concordance was observed with conventional genotyping in RA patients
      both for HLA-DR SE and B27 genotypes. Seventy-three percent of the patients with
      destructive RA had at least one susceptible allele within SE, compared to 38% of
      those patients with non-destructive disease. This new assay, which requires
      minute amount of blood, could be used to determine the genetic background of
      inflammatory arthritis, particularly in non-specialized settings and for large
      scale clinical trials.

PMID- 11516755
TI  - Confocal fluorescent intravital microscopy of the murine spleen.
AB  - Intravital microscopy has provided many insights into cellular interactions in
      various secondary lymphoid tissues. Because this technique allows for the
      visualization of cellular movement in real-time, it has been very powerful.
      However, until now, it has been difficult to apply this technique to the spleen.
      We report a technique that utilizes the Nikon RCM-8000 scanning laser, confocal
      microscope that allows for visualization of cellular movement in real-time in the
      rodent spleen. Using fluorescently labeled high molecular weight dextran or
      monoclonal antibodies, we are able to visualize fluorescently labeled cells
      rolling, tethering, and adhering in the spleen. In addition, we show that the
      majority of blood flow to the spleen remains within the white pulp nodules, as do
      most transferred erythrocytes at early time points. This is the first report of
      intravital microscopy of the spleen using a method that allows for easy
      identification of transferred cells.

PMID- 11516756
TI  - Detection of beta-defensins secreted by human oral epithelial cells.
AB  - Human beta-defensins are antimicrobial peptides that may be critical in the
      innate immune response to infection. hBD1 and hBD2 are expressed in oral
      epithelial cells and are detected near the surface of oral tissue, consistent
      with a role in the epithelial protective barrier function. In this report, we
      examine secretion of beta-defensins in vitro and in biological fluid using
      ProteinChip(R) Array, surface enhanced laser desorption/ionization (SELDI)
      technology combined with time-of-flight mass spectrometry. We show that the 47
      amino acid form of hBD1 and the 41-amino acid form of hBD2 are the major secreted
      forms. These forms are both expressed and secreted under conditions anticipated
      from previous analysis of beta-defensin mRNAs; specifically, hBD1 is detected in
      culture supernatant from both unstimulated and stimulated cells, and hBD2 is
      detected only in stimulated cells. Identity of hBD1 and hBD2 was confirmed by
      immunocapture on the ProteinChip surface. Both peptides are also present in
      gingival crevicular fluid that accumulates between the tissue and tooth surface,
      although hBD1 is also found in several smaller forms suggesting extracellular
      proteolysis. This methodology offers several technical advantages for detection
      of defensins in biological fluids, including ease and speed of screening, no need
      for HPLC preliminary processing, and small sample size.

PMID- 11516757
TI  - Functional quantification of cyclosporine A and FK506 in human whole blood by
      flow cytometry, using the green fluorescent protein as an interleukin-2 reporter
      gene.
AB  - The concentration of the immunosuppressive drugs cyclosporine A (CSA) and FK506
      in biological fluids is routinely determined by antibody-based assays, which for
      several reasons do not give accurate information on the actual level of
      immunosuppression in the patient. To alleviate this problem, we developed a
      functional reporter gene assay which uses the enhancer fragment of the
      interleukin-2 promoter region driving the expression of the green fluorescent
      protein (GFP). This construct was stably transfected in the Jurkat human T
      lymphoblastoid cell line. Upon stimulation of the cell recipient, the GFP was
      produced and evaluated by flow cytometry. Immunosuppressants acting via
      inhibition of interleukin-2 synthesis, such as CSA or FK506, inhibited the
      production of GFP in a dose-dependent manner. This assay can be performed within
      a working day with a good reproducibility and was more sensitive than the
      antibody-based assays, since its detection limit was as low as 10 ng/ml for CSA
      and 0.5 ng/ml for FK506. We used it for the follow up of drug level present in
      the blood of transplanted patients, and compared the results with those obtained
      with the antibody-based assay routinely carried out in our hospital. The
      conclusions suggest that this assay is a valuable alternative to the presently
      available assays for the measurement of the immunosuppressive activity found in
      body fluids.

PMID- 11516758
TI  - Normal T-cell response and in vivo magnetic resonance imaging of T cells loaded
      with HIV transactivator-peptide-derived superparamagnetic nanoparticles.
AB  - The present study analyzed the feasibility of using magnetic resonance imaging
      (MRI) to monitor T-cell homing in vivo after loading T cells with
      superparamagnetic iron oxide (CLIO) nanoparticles derivatized with a peptide
      sequence from the transactivator protein (Tat) of HIV-1. T cells were isolated
      from C57BL/6 (B6) mice and loaded with 0, 400, 800, 1600, or 8000 ng/ml of FITC
      conjugated CLIO-Tat (FITC-CLIO-Tat). There was a dose-dependent uptake of FITC
      CLIO-Tat by T cells. Stimulation of FITC-CLIO-Tat loaded T cells with anti-CD3
      (0.1 microg/ml) plus IL-2 (5 ng/ml) elicited normal activation and activation
      induced cell death (AICD) responses, and normal upregulation of CD69, ICAM-1
      (CD54), L-selectin (CD62L), and Fas. The FITC-CLIO-Tat loaded T cells (3 x 10(7))
      were transferred intravenously (i.v.) into B6 mice and the in vivo MRI of mice
      was acquired using a spin-echo pulse sequence at 4.7 T with a Bruker Biospec
      system. Homing of T cells into the spleen was observed by a decrease in MRI
      signal intensity within 1 h after the transfer, which remained decreased for 2-24
      h after transfer. These homing data were confirmed by FACS analysis and
      biodistribution analysis using 125I-CLIO-Tat. Thus, T cells can be efficiently
      loaded with FITC-CLIO-Tat without interfering with their normal activation and
      AICD, or homing to the spleen, and the biodistribution of FITC-CLIO-Tat loaded T
      cells can be monitored in vivo over time by MRI.

PMID- 11516759
TI  - T-cell antigen discovery (T-CAD) assay: a novel technique for identifying T cell
      epitopes.
AB  - The identification of T cell epitopes is a critical step in evaluating and
      monitoring T cell mediated immune responses. Here, we describe a novel technique
      for simultaneously identifying class I and class II MHC restricted epitopes using
      a one-step protein purification system. This method uses Ni/chelate coated
      magnetic beads and magnetic separation to isolate poly-histidine tagged
      recombinant antigen from bacterial lysates. These beads, once coated with
      antigen, are also used to deliver antigen to APC where it is processed and
      presented to T cells. A colorimetric assay and ovalbumin specific, lacZ
      inducible, T cell hybridomas were used to validate the system. Further, using PSA
      specific hybrids, generated from T cells isolated from PSA secreting tumors, both
      class I and class II MHC restricted epitopes of PSA were identified. Additional
      characterization has shown that these peptides contribute significantly to the
      overall PSA specific response in vivo, and may represent the dominant epitopes of
      PSA.

PMID- 11516760
TI  - Recombinant fusion proteins for haemagglutination-based rapid detection of
      antibodies to HIV in whole blood.
AB  - Recombinant fusion proteins, consisting of a monovalent anti-human RBC monoclonal
      antibody B6, and conserved immunodominant peptide of HIV-1 envelope glycoprotein
      gp41 or HIV-2 envelope glycoprotein gp36, have been designed and purified after
      over-expression in E. coli. These fusion proteins are Fab-based and were obtained
      by assembling the light chain with Fd (variable domain and the first constant
      domain of the heavy chain) or Fd fusions containing HIV-derived peptide, and
      following a protocol of in vitro denaturation of inclusion bodies and subsequent
      renaturation to assemble functional Fab. Using a multistep column chromatographic
      procedure, monomeric Fab and Fab fusion proteins containing HIV-derived peptide
      were purified to high degree, free of aggregates. The yield of various proteins
      on the laboratory scale (1-2 l of shake flask culture) was in the range of tens
      of milligram. Purified anti-human RBC Fab fusion proteins containing sequences
      derived from HIV-1 gp41 and HIV-2 gp36 were highly specific for detection of
      antibodies to HIV-1 and HIV-2, respectively. The described design, expression and
      purification protocols will make it possible to produce specific recombinant
      reagents in large quantities for agglutination-based rapid detection of
      antibodies to HIV in whole blood.

PMID- 11516761
TI  - Evaluation of bioavailability of three types of IFNbeta in multiple sclerosis
      patients by a new quantitative-competitive-PCR method for MxA quantification.
AB  - Intracellular expression of human myxovirus protein A (MxA) is exclusively
      induced by type I IFNs (IFNalpha,beta,omega) or by some viruses and it is
      strongly increased under IFN treatment. We set up an internally controlled
      quantitative-competitive polymerase chain reaction (qc-PCR) that quantifies MxA
      mRNA expressed in human peripheral blood mononuclear cells (PBMC). Our qc-PCR is
      accurate because the mean ratio of copy number estimated by qc-PCR to that
      quantified spectrophotometrically is 1.08+/-0.03, moreover it is repeatable with
      high sensitivity (1 fg MxA/pg GAPDH). MxA mRNA was tested in 47 Relapsing
      Remitting Multiple Sclerosis (RR-MS) untreated patients and in 48 patients
      treated with one of the 3 IFNbeta licensed for MS (24 with Rebif, 14 with Avonex
      and 10 with Betaferon). All the 48 treated patients were negative to IFNbeta
      neutralising antibodies (NABs) as tested in our laboratory using a cytopathic
      assay (CPE). MxA mRNA levels were detectable in all untreated patients (mean 24+/
      18 fg MxA/pg GAPDH) and significantly higher levels were found in all the treated
      patients 12 h after IFNbeta administration (mean 499+/-325 fg MxA/pg GAPDH);
      furthermore, the three types of IFNbeta showed comparable bioavailability. Our
      data indicate that the bioavailability of the three available types of IFNbeta
      can be evaluated by MxA qc-PCR.

PMID- 11516762
TI  - Sleep and wakefulness in somnambulism: a spectral analysis study.
AB  - OBJECTIVE: The sleep structure and the dynamics of EEG slow-wave activity (SWA)
      were investigated in 12 young adults and age- and gender-matched controls.
      METHODS: Polysomnography was performed in subjects with well-documented chronic
      sleepwalking and in matched controls. Blinded visual scoring was performed using
      the international criteria from the Rechtschaffen and Kales atlas [A manual of
      standardized technology, techniques and scoring systems for sleep stages of human
      subjects. Los Angeles: UCLA Brain Information Service, Brain Research Institute,
      1968.] and by determining the presence of microarousals as defined in the
      American Sleep Disorders Association (ASDA) atlas [Sleep 15 (1992) 173.]. An
      evaluation of SWA overnight was performed on total nocturnal sleep to determine
      if a difference existed between groups of subjects, since sleepwalking usually
      originates with slow-wave sleep. Investigation of the delta power in successive
      nonoverlapping 4-second windows in the 32 seconds just prior to EMG activity
      associated with a confusional arousal was also conducted. One central EEG lead
      was used for all analyses. RESULTS: Somnambulistic individuals experienced more
      disturbed sleep than controls during the first NREM-REM sleep cycle. They had a
      higher number of ASDA arousals and presented lower peak of SWA during the first
      cycle that led to a lower SWA decline overnight. When the investigation focused
      on the short segment immediately preceding a confusional arousal, they presented
      an important increase in the relative power of low delta (0.75-2 Hz) just prior
      to the confusional arousal. CONCLUSION: Sleepwalkers undergo disturbed nocturnal
      sleep at the beginning of the night. The increased power of low delta just prior
      to the confusional arousal experienced may not be related to Stages 3-4 NREM
      sleep. We hypothesize that it may be translated as a cortical reaction to brain
      activation.

PMID- 11516763
TI  - The Family Response Questionnaire: a new scale to assess the responses of family
      members to people with chronic fatigue syndrome.
AB  - OBJECTIVE: Family responses to patients with chronic fatigue syndrome (CFS) may
      influence the course of the disorder and family members themselves are likely to
      be adversely affected. However, the beliefs and responses of relatives of CFS
      patients have been under-researched. The aim of this study was to produce an easy
      to-administer questionnaire to assess the responses of family members to people
      with CFS. METHODS: Seventy-eight people, all close relatives of (physician
      diagnosed) CFS sufferers, completed the first version of the Family Response
      Questionnaire (FRQ). RESULTS: Examination of the correlation matrix and a cluster
      analysis of the items support four scales rather than the original five. The four
      response scales were labelled: sympathetic-empathic, active engagement, rejecting
      hostile, and concern with self. Measures of test-retest and internal reliability
      were high. Participants found the items both comprehensible and relevant to their
      experiences of living with people with CFS. CONCLUSION: The new version of the
      FRQ will be useful in further examination of the responses of CFS on individuals
      and their families.

PMID- 11516764
TI  - The use of a symptom "self-report" inventory to evaluate the acceptability and
      efficacy of a walking program for patients suffering with chronic fatigue
      syndrome.
AB  - OBJECTIVES: The purpose of this research was to evaluate the effectiveness of the
      modality of walking as a management strategy for patients suffering with chronic
      fatigue syndrome (CFS). METHODS: Six males and fourteen females with medically
      diagnosed CFS (CDC, 1994), completed a 12-week walking program. Prior to starting
      the program subjects underwent an incremental walking exercise test to
      predetermine their walking intensity. The SCL-90-R symptom "self-report"
      questionnaire was administered prior to, and at the completion of, the walking
      program. RESULTS: At the completion of the 12 weeks of walking, changes in four
      of the nine SCL-90-R dimensions were significant (somatisation, paranoid
      ideation, phobic anxiety, and psychoticism). Also significant were the changes in
      the combination indices, the Global Indices of Distress (GID) and the Positive
      Symptom Total (PST). CONCLUSION: This group of CFS subjects, by way of "self
      report", indicated the possibility of an exercise-induced decrease in
      psychological stress. The walking intervention may have evoked positive changes
      in their well-being and, furthermore, provided no evidence of any exacerbation in
      their symptoms.

PMID- 11516765
TI  - Health-related quality of life in patients with chronic fatigue syndrome: an
      international study.
AB  - OBJECTIVE: Chronic fatigue syndrome (CFS) has been reported worldwide. Our
      objectives were to determine if patients from different countries have similar
      profiles of impairments. METHODS: Health-related quality of life (HRQoL) was
      assessed in 740 CFS patients in the US, 82 in the UK, and 65 in Germany using the
      eight subscales of the Short-Form General Health Survey (SF-36). To examine the
      internal structure, factor analyses were performed. RESULTS: Overall, there was a
      remarkable similarity in HRQoL among all CFS patients, regardless of location.
      Patients scored two to three standard deviations below normal on six subscales
      and one standard deviation below normal on the other two subscales. Factor
      analysis suggested a two-factor model where the same six subscales constitute the
      first factor and the two others the second factor. CONCLUSION: HRQoL is poor in
      CFS patients from three countries. This study is a first step towards conducting
      further comparative cross-cultural and international studies.

PMID- 11516766
TI  - Self-reported hyperarousal traits among insomnia patients.
AB  - Hyperarousal Scale scores for certain self-reported behaviors reportedly
      correlate with EEG arousal measures. We tested whether an insomnia subject group
      had different Hyperarousal Scale scores compared with hypersomnia, delayed sleep
      phase syndrome, procrastinator or normal subject groups. Compared with 139 normal
      subjects, mean scores for a group of 256 insomnia subjects was significantly 1.2
      S.D. higher on Hyperarousal total scale score, 0.82 S.D. higher on React subscale
      score and 0.85 S.D. higher on Introspectiveness subscale score. The insomnia
      group median Extreme score was 2.25 times that of the normal group. These self
      report findings suggest that insomnia subjects may be more responsive generally.
      All sleep disorder groups had increased total Hyperarousal scores, although these
      increases were accounted for by different scale items. The procrastinator group
      had Hyperarousal score patterns that generally differed from those of the other
      groups.

PMID- 11516767
TI  - Increased vital exhaustion among type-D patients with ischemic heart disease.
AB  - OBJECTIVE: To investigate the prevalence of the "distressed personality" (type-D)
      in cardiac patients and to explore the relationships between type-D, gender,
      vital exhaustion and angina pectoris. METHODS: A questionnaire was completed by
      171 patients scheduled for coronary angiography (CAG) at baseline and again at 6
      weeks following implementation of treatment with invasive procedures or
      medication. RESULTS: Women were more vitally exhausted at baseline and more
      likely to be classified as type-D. Type-D patients scored higher on vital
      exhaustion independent of all other variables. Angina was related to vital
      exhaustion, but improvement in angina following intervention was not associated
      with improvement in vital exhaustion scores. CONCLUSION: Although medical
      interventions reduced angina, a concomitant decrease in vital exhaustion scores
      was not found. It is suggested that type-D may explain gender differences on
      distress. Clinical implications are discussed, including the importance of
      including personality factors in future research, as they have been shown to have
      independent prognostic value.

PMID- 11516768
TI  - Dreams in obsessive-compulsive disorder: an analysis of semantic and emotional
      content compared to controls.
AB  - OBJECTIVE: We sought to investigate the content of the dreams of obsessive
      compulsive outpatients in the light of the following postulate: if dreams play a
      role in the processing of information and mental storage of events of the day,
      the dream recollections of obsessive-compulsive disorder (OCD) patients should
      present evidence of diurnal obsessive or ritual themes. METHOD: On seven
      successive mornings, immediately after awakening in their home environment, 10
      nondepressed OCD patients and 11 controls recorded their recollections of the
      night's dreams on an audiotape. After randomization of dreams, two judges were
      asked to carry out a blind evaluation of the emotional characteristics
      perceptible in these dreams and the presence of obsessive or ritual themes.
      RESULTS: 47 dreams were collected in the OCD group and 55 in the control group.
      No differences were found between the two groups regarding anxiety, sadness, the
      theme of failure, or the presence of obsessive or ritual themes. About 60% of OCD
      patients and 73% of the control group recounted dreams expressing anxiety,
      sadness, or failure. Most surprisingly, in the control group as well as in the
      OCD group, about one-third of subjects presented obsessive or ritual themes in
      their dreams. CONCLUSION: These data suggest that there is no evident link
      between diurnal mental activity and the morning recollection of nocturnal dreams
      regarding anxiety, failure, sadness, and obsessive-compulsive themes.

PMID- 11516769
TI  - Methamphetamine neurotoxicity: necrotic and apoptotic mechanisms and relevance to
      human abuse and treatment.
AB  - Research into methamphetamine-induced neurotoxicity has experienced a resurgence
      in recent years. This is due to (1) greater understanding of the mechanisms
      underlying methamphetamine neurotoxicity, (2) its usefulness as a model for
      Parkinson's disease and (3) an increased abuse of the substance, especially in
      the American Mid-West and Japan. It is suggested that the commonly used
      experimental one-day methamphetamine dosing regimen better models the acute
      overdose pathologies seen in humans, whereas chronic models are needed to
      accurately model human long-term abuse. Further, we suggest that these two dosing
      regimens will result in quite different neurochemical, neuropathological and
      behavioral outcomes. The relative importance of the dopamine transporter and
      vesicular monoamine transporter knockout is discussed and insights into oxidative
      mechanisms are described from observations of nNOS knockout and SOD
      overexpression. This review not only describes the neuropathologies associated
      with methamphetamine in rodents, non-human primates and human abusers, but also
      focuses on the more recent literature associated with reactive oxygen and
      nitrogen species and their contribution to neuronal death via necrosis and/or
      apoptosis. The effect of methamphetamine on the mitochondrial membrane potential
      and electron transport chain and subsequent apoptotic cascades are also
      emphasized. Finally, we describe potential treatments for methamphetamine abusers
      with reference to the time after withdrawal. We suggest that potential treatments
      can be divided into three categories; (1) the prevention of neurotoxicity if
      recidivism occurs, (2) amelioration of apoptotic cascades that may occur even in
      the withdrawal period and (3) treatment of the atypical depression associated
      with withdrawal.

PMID- 11516770
TI  - Elements of cerebral microvascular ischaemia.
AB  - Although neuronal cells have long been thought to be the prime target of
      ischaemic insults, events which occur at the blood-vascular-parenchymal interface
      are necessary for the initiation of ischaemic tissue injury. This cascade of
      microvascular events includes fibrin accumulation, endothelium expression of
      leukocyte adhesion receptors, breakdown of the basal laminae with loss of
      astrocyte and endothelial cell contacts leading to blood-brain barrier disruption
      and consequently oedema formation and haemorrhagic transformation. Potential
      stroke treatments have been studied in the clinic and many have not been
      particularly successful, probably due to the delicate balance between improved
      outcome and adverse reactions as well as the window of opportunity for drug
      treatment after symptom onset. The only acute intervention trial demonstrating
      any benefit in patients was that of intravenous tissue plasminogen activator
      (tPA), administered within 3 h of the onset of symptoms of ischaemic stroke. Such
      treatment improved clinical outcome at 3 months, although there was an increased
      incidence of symptomatic haemorrhage [New Engl. J. Med. 333 (1995) 1581]. The
      recent progress made in defining the mechanisms involved in the initiation of
      ischaemic events, as described in this review, may lead to the identification of
      new strategies for intervention in the ischaemic cascade.

PMID- 11516771
TI  - The angiotensin system elements in invertebrates.
AB  - In this review, the different components of the renin-angiotensin system (RAS) in
      invertebrates are discussed. This system is implicated in osmoregulation,
      reproduction, memory processes and immune system regulation. As the elements of
      this hormone-enzymatic system also exist in invertebrates, it appears that the
      RAS originated very early in evolution.

PMID- 11516772
TI  - Neurobiology of fish olfaction: a review.
AB  - The last decade saw important advances in our understanding of the olfactory
      system function. In some animals, we now have the basic knowledge necessary to
      investigate coding mechanisms employed in olfaction. So far, studies of the fish
      olfactory system have focused on odor detection and the early processing of
      olfactory information in the olfactory bulb. How this information is integrated
      in the forebrain is unknown. Here, we first describe the anatomy of the fish
      olfactory system. The problems faced when describing the anatomy of the terminal
      nerve complex and nucleus olfactoretinalis are highlighted. Olfactory sensory
      neurons are randomly distributed over the entire olfactory epithelium, a unique
      feature of the olfactory sense. These primary olfactory neurons converge upon
      their second-order targets in segregated areas of the olfactory bulb. Exchange of
      information occurs in the glomeruli and glomerular plexus, where primary neurons
      synapse on mitral cell dendrites. The spatial distribution of glomerular activity
      induced by odorants of different classes shows that distinct neuron populations
      of the olfactory bulb encode information related to different odorant groups. In
      most cases, these neuron populations synchronize their alternating sequences of
      firing and silence when stimulated by primary input. Synchronized oscillations of
      these second-order neurons could contain important coding information, or
      represent a mechanism by which learning is facilitated. Alternatively,
      oscillations could be solely used to shape the olfactory bulb response. The
      nature of the olfactory information that reaches the forebrain and decoding of
      this information by the central nervous system are discussed.

PMID- 11516773
TI  - Applications of the Morris water maze in the study of learning and memory.
AB  - The Morris water maze (MWM) was described 20 years ago as a device to investigate
      spatial learning and memory in laboratory rats. In the meanwhile, it has become
      one of the most frequently used laboratory tools in behavioral neuroscience. Many
      methodological variations of the MWM task have been and are being used by
      research groups in many different applications. However, researchers have become
      increasingly aware that MWM performance is influenced by factors such as
      apparatus or training procedure as well as by the characteristics of the
      experimental animals (sex, species/strain, age, nutritional state, exposure to
      stress or infection). Lesions in distinct brain regions like hippocampus,
      striatum, basal forebrain, cerebellum and cerebral cortex were shown to impair
      MWM performance, but disconnecting rather than destroying brain regions relevant
      for spatial learning may impair MWM performance as well. Spatial learning in
      general and MWM performance in particular appear to depend upon the coordinated
      action of different brain regions and neurotransmitter systems constituting a
      functionally integrated neural network. Finally, the MWM task has often been used
      in the validation of rodent models for neurocognitive disorders and the
      evaluation of possible neurocognitive treatments. Through its many applications,
      MWM testing gained a position at the very core of contemporary neuroscience
      research.

PMID- 11516775
TI  - Nasal vaccination: a non-invasive vaccine delivery method that holds great
      promise for the future.

PMID- 11516776
TI  - The nose and paranasal sinuses physiology and anatomy.
AB  - The paranasal sinuses and nose are much more than two cavities behind a
      projection on the centre of the face. They humidify, filter, warm, and sense what
      we breathe. The anatomy and physiology interact forming a dynamic system. The
      anatomy, airflow, nasal resistance, its turbulence, the nasal cycle - a process
      by which the turbinates or cushions lining the nose alternatively swell and
      congest from side to side, can all potentially influence the nasal delivery of
      drugs. Along with these factors mucus rheology and mucociliary clearance
      influence the removal of substances delivered to the nose. The health of the nose
      and its immunological response to what is inhaled, be it pollutants, allergens,
      drugs or vaccines, all need to be considered. It is a fascinating sensor for the
      body, not only detecting the potentially harmful substances such as smoke, but
      its psychosexual aspects have far reaching implications and the olfactory pathway
      has potential as a pathway for the delivery of drugs.

PMID- 11516777
TI  - Nasal vaccines.
AB  - The nasal route for vaccination offers some important opportunities, especially
      for the prophylaxis of respiratory diseases. Vaccination via the respiratory
      tract is reviewed and the deposition and clearance of antigens in the deep lung
      and nose are described and contrasted. Lymphoid structures in the respiratory
      tract differ according to species; the rat and mouse have a well developed nose
      associated lymphoid tissue, while in man, the structure known as Waldeyer's ring
      (that includes the tonsils), is important as an induction site. The immune
      response following intranasal administration can provide protection at the
      administration site and at various effector sites as part of the common mucosal
      immune system. A number of formulation considerations are important when
      designing novel systems for nasal administration as are physiological factors
      such as mucociliary clearance.

PMID- 11516778
TI  - Manipulating the immune system: humoral versus cell-mediated immunity.
AB  - Many of the vaccines in use today were designed on an empirical basis with little
      understanding of the mechanism of protective immunity or knowledge of the
      protective antigens. Certain of these vaccines, based on killed or attenuated
      bacteria or viruses, are associated with unacceptable side-effects. New
      generation vaccines based on recombinant proteins or naked DNA have considerably
      improved safety profiles, but are often poorly immunogenic, especially when
      administered by mucosal routes. This is a particular problem with oral delivery;
      where high doses of antigen are required to generate even modest immune
      responses. In contrast, nasal delivery of antigens with a range of adjuvants or
      delivery systems has been shown to generate relatively potent immune responses
      and to protect against infection in animal models. Advances in immunology have
      demonstrated that a variety of cellular and humoral immune effector mechanisms,
      that are regulated by distinct Th1 and Th2 subtypes of T cells, mediate
      protection against different infectious diseases. The identification of adjuvants
      and immunomodulators, that can promote the selective induction of these distinct
      populations of T cells, has now made it possible to rationally design safe and
      effective mucosal vaccines against a range of infectious diseases of man.

PMID- 11516779
TI  - Nasal vaccination using live bacterial vectors.
AB  - Live recombinant bacteria represent an attractive means to induce both mucosal
      and systemic immune responses against heterologous antigens. Several models have
      now been developed and shown to be highly efficient following intranasal
      immunization. In this review, we describe the two main classes of live
      recombinant bacteria: generally recognized as safe bacteria and attenuated
      strains derived from pathogenic bacteria. Among the latter, we have
      differentiated the bacteria, which do not usually colonize the respiratory tract
      from those that are especially adapted to respiratory tissues. The strategies of
      expression of the heterologous antigens, the invasiveness and the immunogenicity
      of the recombinant bacteria are discussed.

PMID- 11516780
TI  - Cytokines as adjuvants for the induction of mucosal immunity.
AB  - Safe nasal vaccines capable of promoting both mucosal and systemic immunity are
      needed for effective protection against bacterial and viral pathogens. While
      parenteral cytokine treatment could lead to unwanted toxicity, the nasal delivery
      route results in low but biologically active serum cytokine levels. Interleukin
      (IL)-6, IL-1 and IL-12, which promote either Th2- or Th1-type responses,
      respectively, also enhance systemic immunity to co-administered antigens. The
      chemoattractants lymphotactin (Lptn), RANTES and defensins also exerted adjuvant
      activity for systemic immunity when nasally administered with antigens. However,
      each cytokine or innate factor promoted a distinct pattern of T helper cell
      responses and corresponding IgG subclass response. Interleukin-12, IL-1, and the
      chemokines Lptn and RANTES promote mucosal immunity. In contrast, nasal IL-6 and
      defensins failed to induce mucosal S-IgA Ab responses, suggesting that mechanisms
      more complex than T cell activation and chemotaxis are required for the
      development of mucosal immunity after nasal delivery of cytokines.

PMID- 11516781
TI  - Chitosan as a novel nasal delivery system for vaccines.
AB  - A variety of different types of nasal vaccine systems has been described to
      include cholera toxin, microspheres, nanoparticles, liposomes, attenuated virus
      and cells and outer membrane proteins (proteosomes). The present review describes
      our work on the use of the cationic polysaccharide, chitosan as a delivery system
      for nasally administered vaccines. Several animal studies have been carried out
      on influenza, pertussis and diphtheria vaccines with good results. After nasal
      administration of the chitosan-antigen nasal vaccines it was generally found that
      the nasal formulation induced significant serum IgG responses similar to and
      secretory IgA levels superior to what was induced by a parenteral administration
      of the vaccine. Animals vaccinated via the nasal route with the various chitosan
      antigen vaccines were also found to be protected against the appropriate
      challenge. So far the nasal chitosan vaccine delivery system has been tested for
      vaccination against influenza in human subjects. The results of the study showed
      that the nasal chitosan influenza vaccine was both effective and protective
      according to the CPMP requirements. The mechanism of action of the chitosan nasal
      vaccine delivery system is also discussed.

PMID- 11516782
TI  - Polymeric lamellar substrate particles for intranasal vaccination.
AB  - In recent years, several strategies have been under investigation to achieve safe
      and effective immunisation, in terms of new antigens, adjuvants and routes of
      vaccination. The latter include mucosal sites such as oral, rectal, vaginal and
      nasal. Biodegradable microparticles produced from polymers such as poly(D,L
      lactide) (PLA) and poly(D,L-lactide-co-glycolide) (PLGA) containing encapsulated
      vaccine antigens have been extensively studied for immunisation. These
      microparticles allow controlled release of vaccines with the aim to develop as
      single dose vaccines. However there are concerns regarding the integrity and
      immunogenicity of the antigen during the encapsulation process when the antigen
      is exposed to organic solvents, high shear stresses and the exposure of antigen
      to low pH which is caused by polymer degradation. Polymeric lamellar substrate
      particles (PLSP) produced by simple precipitation of PLA, form a novel polymeric
      system for the adsorption of antigens. This procedure avoids pH changes, exposure
      to organic solvents and hence allows the integrity of the antigen to be retained.
      The aim of this article is to discuss the factors affecting the characteristics
      of PLSP and adsorption of antigens onto PLSP and consider their potential as
      adjuvants for the nasal delivery of protein, peptide or viral vaccines.

PMID- 11516783
TI  - Synthetic biomimetic supra molecular Biovector (SMBV) particles for nasal vaccine
      delivery.
AB  - For the optimal delivery of antigens to mucosal tissues, especially as nasal
      sprays, protein antigen alone is often not sufficient. A clear need for nasal
      delivery systems has therefore evolved, especially for Influenza A vaccines. Such
      technologies will be even more essential for new modern vaccines based on
      recombinant antigens. Here we describe synthetic biomimetic supra molecular
      Biovector (SMBV) which have proven in preclinical and clinical evaluation to be
      suitable candidates for the delivery of nasal vaccines. They also demonstrate the
      potential to work with multiple antigens and furthermore allow combination with
      adjuvants. These Biovectors can associate with internal or lipid layer membrane
      proteins and peptides due to their charged polysaccharide core. The mimicry with
      viruses is also provided through their size of 60-80 nm, which allows
      sterilization by filtration. This makes them an ideal tool for the development of
      modern nasal vaccines, as they have shown to be able to induce the desired types
      of humoral immunity (serosal and mucosal immunity, IgA and IgG antibodies) as
      well as cellular immunity (CD4 and CD8 responses).

PMID- 11516784
TI  - Microparticles for intranasal immunization.
AB  - Of the several routes available for mucosal immunization, the nasal route is
      particularly attractive because of ease of administration and the induction of
      potent immune responses, particularly in the respiratory and genitourinary
      tracts. However, adjuvants and delivery systems are required to enhance immune
      responses following nasal immunization. This review focuses on the use of
      microparticles as adjuvants and delivery systems for protein and DNA vaccines for
      nasal immunization. In particular we discuss our own work on poly(lactide co
      glycolide) (PLG) microparticles with entrapped protein or adsorbed DNA as a
      vaccine delivery system. The possible mechanisms involved in the enhancement of
      immune responses through the use of DNA adsorbed onto PLG microparticles are also
      discussed.

PMID- 11516785
TI  - Bacteria-derived particles as adjuvants for non-replicating nasal vaccines.
AB  - In attempts to mimic natural infections, vaccines consisting of microbial
      particles may be delivered directly to mucosal surfaces. In this way, the mucosal
      as well as the systemic immune systems can be activated. Even non-living
      particles of bacterial origin have been shown to elicit strong immune responses
      when administered intranasally. However, some particles such as formalin
      inactivated influenza virus may need a mucosal adjuvant to be effective. The
      bacteria-derived particles seem to possess such an adjuvant activity when mixed
      with and given intranasally with the less immunogenic killed virus. Possibly, the
      bacterial particles facilitate uptake of the virus through the mucosal membranes,
      although an additional influence on the immune response to the virus might be
      mediated in the lymphoid tissue below the mucosal surface. Bacteria-derived
      particles in nasal vaccines may thus serve as an alternative adjuvant to
      derivatives of cholera toxin or the heat-labile toxin from E. coli.

PMID- 11516786
TI  - Immunostimulating complexes (ISCOMs) for nasal vaccination.
AB  - The immunostimulating complex (ISCOM) is documented as a strong adjuvant and
      delivery system for parenteral immunization. Its effectiveness for mucosal
      immunization has also been proven with various incorporated antigens. Lovgren et
      al. were the first to demonstrate the capacity of influenza virus ISCOMs to
      induce mucosal immune response and protection after one comparatively low nasal
      dose. Further studies show that similar to Cholera toxin (CT) and Escherichia
      coli heat-labile toxin (LT), ISCOMs break immunological tolerance and exert
      strong mucosal adjuvant activity, resulting in secretory IgA and systemic immune
      responses. Striking is the capacity of ISCOMs to induce CTL response also after
      nasal administration. In contrast to CT, ISCOMs initiate mucosal as well as
      systemic immune responses in an IL-12 dependent manner but independently of IL-4.
      The recombinant B subunit of cholera toxin (rCTB) was incorporated in the same
      ISCOM particle to explore symbiotic effects. The IgA response to rCTB in lungs
      was increased 100-fold when rCTB was administered nasally in ISCOMs and more than
      10-fold in the remote mucosa of the genital tract. An enhanced IgA response to a
      passenger antigen OVA was recorded in the remote genital tract. After i.n.
      administration of the envelope proteins of respiratory syncytial virus in ISCOMs,
      high serum antibodies were induced, almost at the same levels as those following
      parenteral immunization and potent IgA responses were also evoked both at the
      local respiratory mucosa, and in the cases tested at the distant mucosae of the
      genital and intestinal tracts. Similar results have also been recorded with
      ISCOMs containing envelope proteins from Herpes simplex virus, Influenza virus
      and Mycoplasma mycoides. The mucosal targeting property of envelope proteins of
      RSV was utilized in an HIV-gp120 RSV ISCOM formulation. After nasal
      administration an enhanced mucosal IgA response to gp120 was observed in the
      female reproductive tract. In general, antigens derived from envelope viruses or
      cell membranes incorporated into ISCOMs retain their biological activity and
      conformation, encompassing the mucosal targeting and virus neutralizing
      properties.

PMID- 11516787
TI  - Nasal delivery of epitope based vaccines.
AB  - Essentially all of the currently available vaccines are based on the use of
      inactivated or live-attenuated pathogens. However, these vaccines have several
      shortcomings, such as difficulties of in vitro culturing, biohazard risks, as
      well as loss of efficacy due to the genetic variations seen in many viruses.
      These problems may potentially be solved by immunising with epitope-based
      vaccines consisting of rationally designed protective epitopes, appropriately
      presented and easy to deliver, which are capable of stimulating effective B-cell,
      T-cell and cytotoxic immune responses whilst avoiding potentially hazardous and
      undesirable effects. Furthermore, the use of a mixture of defined epitopes could
      lead to an effective broad range immune response which has the potential to
      overcome both strain specificity of the pathogen and the MHC restriction of the
      host. Epitope-based vaccines can be designed to involve the use of synthetic
      materials that can be available in unlimited quantities and posing no biohazard.
      Other approaches include the use of naked DNA or recombinant viruses or bacteria
      expressing the epitopes. An important objective in the development of such
      vaccines is that they should be effective when delivered via the mucosal route
      and effective in the presence of maternal antibodies. In this review, we present
      examples of the use of various epitope-based vaccine constructs, focussing
      particularly upon their intranasal delivery to the immune system.

PMID- 11516788
TI  - Intranasal vaccination against plague, tetanus and diphtheria.
AB  - Plague is an extremely virulent and potentially lethal infection caused by the
      bacterium Y. pestis. The current vaccine used to immunise against plague often
      fails to engender solid (100%) protection against inhalational infection with Y.
      pestis. Similarly, logistical factors favour the development of non-parenteral
      immunisation protocols to counter plague. Recently an improved parenteral
      vaccination strategy for plague, based on the recombinant subunit approach, has
      entered clinical trails. The Yersinia pestis subunit antigens (F1 and V) have
      been successfully incorporated into novel vaccine delivery systems such as
      biodegradable microspheres composed of poly-L-(lactide) (PLLA). Intranasal and
      intratracheal administration of PLLA microencapsulated F1 and V serves to protect
      experimental animals from inhalational and subcutaneous challenge with virulent
      Y. pestis bacilli. Liposomes have also been used to improve the immunogenicity of
      intranasally administered Y. pestis antigens, and the effectiveness of this
      approach to plague immunisation has been evaluated. Tetanus and diphtheria still
      cause many deaths worldwide. The maintenance of protective immunity to diphtheria
      and tetanus requires booster injections of the currently licensed toxoid
      vaccines. Consequently, many people remain unprotected. Improved coverage may
      well result from the development of effective non-invasive vaccines that could be
      readily distributed and potentially self-administered. To this end, the
      intranasal and inhalational routes of administration have been extensively
      investigated. Tetanus and diphtheria toxoids have been delivered intranasally to
      experimental animals using a wide variety of adjuvants (enterotoxin derivatives),
      penetration enhancers (cyclodextrins, bile salts, surfactants, cationic polymers)
      and delivery systems (microspheres and liposomes). As compared with parenteral
      vaccination, nasal immunisation has been shown favourably effective in small
      animal models, and a limited number of early phase clinical trails. As a caveat
      to this, adjuvantisation of toxoid/subunit molecules appears to be a requisite
      for elicitation of appreciable immunological responses, following nasal
      administration of acellular immunogens. Testing in larger animal models and
      humans is needed to ascertain if the promising results obtained in rodents can be
      reciprocated without compromising safety.

PMID- 11516789
TI  - Review of intranasal influenza vaccine.
AB  - Influenza viruses cause costly recurrent annual epidemics. Current efforts to
      control the morbidity and mortality associated with influenza outbreaks are based
      on the use of annual intramuscularly administered inactivated vaccines which are
      not only painful to administer, but are suboptimal in efficacy. This paper
      reviews the composition, safety analysis, rates of adverse events, immune
      response and protective efficacy of a new inactivated intranasal influenza
      vaccine.

PMID- 11516791
TI  - Domestic abuse in a central Mediterranean pregnant population.
AB  - The Mediterranean region is generally characterized by a patriarchal society that
      generally predisposes towards a higher prevalence of spouse abuse. The prevalence
      of domestic spouse abuse in a central Mediterranean closed island community was
      assessed to approximate 11.7% of the pregnant population. The abuse varied from
      psychological to physical abuse. There was a strong history of experience of
      domestic violence/abuse during childhood in both the victim and perpetrator
      suggesting that a "circle of abuse" may play a role in some cases. The socio
      biological characteristics of the victim did not appear to statistically
      predispose towards a higher risk for domestic abuse, though single mothers were
      statistically more likely to report a history of domestic abuse. Abused women
      were more likely to smoke cigarettes during pregnancy than their counterparts.
      The perpetrator was statistically more likely to be unemployed, and smoke
      cigarettes and drink alcohol. There were no statistical correlation between a
      history of spouse abuse and educational level attained by both the victim and
      perpetrator. A history of domestic abuse appears to have an adverse effect on the
      pregnancy with a higher risk of premature birth and its attendant complications;
      although it is difficult to ascertain how much the reported poor obstetric
      outcome is a direct effect of violence itself or to other associated adverse
      social or biological co-factors. About a third of the women interviewed were
      unaware of the domestic violence services being offered in their community
      emphasizing the need of an information drive. The antenatal period, with the
      distribution of leaflets and antenatal classes, is an opportune time to promote
      the support services available in the community.

PMID- 11516792
TI  - Neonatal respiratory morbidity following elective caesarean section in term
      infants. A 5-year retrospective study and a review of the literature.
AB  - Respiratory morbidity is an important complication of elective caesarean section.
      The presence of labour preceding caesarean section reduces the risk of neonatal
      respiratory morbidity. Recently, it has been shown that the incidence of
      respiratory morbidity is lower in infants with a gestational age of at least
      39(+0) weeks at elective caesarean section compared to infants with a gestational
      age less than 39(+0) weeks.This article describes the results of a 5-year
      retrospective study on the incidence of respiratory distress in term neonates
      delivered by elective caesarean section in relation to gestational age and
      provides a literature review on neonatal respiratory morbidity following elective
      caesarean section.

PMID- 11516793
TI  - Umbilical cortisol levels as an indicator of the fetal stress response to
      assisted vaginal delivery.
AB  - OBJECTIVES: While it is well established that delivery by elective caesarean
      section is less stressful for the fetus than normal vaginal delivery, little
      attention has been paid to the effect on the baby of an assisted delivery. STUDY
      DESIGN: We examined cortisol levels in venous cord blood from seven babies born
      by forceps, 10 by ventouse extraction, 28 by unassisted normal vaginal delivery,
      and 12 born by elective caesarean. Paired maternal bloods were taken immediately
      after delivery. RESULTS: Cord blood cortisol values were significantly different
      in the different groups (one-way ANOVA, P < 0.0001). The forceps group had the
      highest values and the caesarean group the lowest; both were different from the
      normal vaginal delivery group (P=0.019 and P=0.046, respectively). There was no
      effect of length of labour, or method of pain relief on cortisol levels. Maternal
      values were similar in the different groups, confirming that the differences
      observed derived from the fetus. CONCLUSIONS: There is increasing evidence that
      the stress experienced by the fetus or neonate can have long-term effects on the
      function of the hypothalamic-pituitary-adrenal axis in later life. We speculate
      that the stress caused by some assisted deliveries may contribute to this.

PMID- 11516794
TI  - Fast track hysterectomy.
AB  - OBJECTIVE: To identify factors limiting early discharge after laparoscopically
      assisted vaginal hysterectomy (LAVH) and abdominal hysterectomy, in a fast track
      setting with emphasis on information, treatment of pain, early mobilization, and
      early food intake. STUDY DESIGN: A prospective, descriptive study of 32
      unselected women allocated to either abdominal hysterectomy (n=16) or LAVH
      (n=16). The patients received the same information, care, and advice for the
      perioperative period except for an assumed 1-day hospital stay in the LAVH-group
      and 2 days in the abdominal group. RESULTS: Patients were discharged median 1 day
      (1-3) after LAVH and 2 days (2-4) after abdominal hysterectomy. Work was resumed
      median 23 days after abdominal hysterectomy and 28 days after LAVH (P > 0.05).
      CONCLUSIONS: The study questions the previously proposed advantages of shortened
      hospitalization and convalescence after LAVH compared with abdominal
      hysterectomy. Further studies with active rehabilitation are needed to
      demonstrate real differences between laparoscopic and open hysterectomy.

PMID- 11516795
TI  - The concentrations of osteocalcin and degradation products of type I collagen in
      pregnant women with pre-eclampsia.
AB  - OBJECTIVES: To investigate the concentrations of osteocalcin and collagen type I
      C-terminal telopeptides in pregnant women with pre-eclampsia. STUDY DESIGN: 26
      patients with severe pre-eclampsia and 24 healthy pregnant women were included in
      the study. Serum concentrations of osteocalcin and C-telopeptides--degradation
      products of type I collagen were determined using the ELISA method. Statistical
      analysis was performed using Mann-Whitney U-test. RESULTS: In pre-eclamptic
      patients, the concentrations of osteocalcin and degradation products of collagen
      type I were significantly higher (P<0.005) when compared to healthy pregnant
      women. CONCLUSION: These results could suggest that there are alterations in bone
      metabolism in pregnant women with pre-eclampsia.

PMID- 11516796
TI  - The Marfan syndrome and pregnancy: a retrospective study in a Dutch population.
AB  - OBJECTIVE: To assess the course and outcome of pregnancies in women with the
      Marfan syndrome with the aim of developing guidelines for counseling. STUDY
      DESIGN: A retrospective study based on data collected from members of the Dutch
      Association of Marfan patients. Pregnancies and neonatal outcomes of affected
      mothers were compared with those of non-affected mothers who delivered a Marfan
      infant. RESULTS: In a group of 44 affected women 78 pregnancies beyond 24 weeks
      of gestation were evaluated, compared with 51 in non-affected women. Obstetric
      course and neonatal outcome of pregnancy were similar in both groups. Aortic
      dissection was observed in five affected women, three of which were known to have
      an aorta diameter of 40 mm or more; two neurovascular events were recorded; all
      mothers survived. CONCLUSIONS: A preconceptional aortic diameter of 40 mm or
      more, progression of dilatation and decreased cardiac function are risk factors
      in pregnancy for women with the Marfan syndrome. A multidisciplinary approach is
      recommended for the care of these patients and their infants.

PMID- 11516797
TI  - Risk factors associated with true knots of the umbilical cord.
AB  - OBJECTIVE: To determine obstetrical risk factors and pregnancy outcome of fetuses
      with true knot of the umbilical cord. METHODS: Study population included 69,139
      singleton deliveries occurring between the years 1990-1997. Data were retrieved
      from the database of the Soroka University Medical Center. Fetuses with
      malformations were excluded. RESULTS: The incidence of true knots was 1.2%
      (841/69,139). In a multivariate analysis the following factors were found to be
      significantly associated with true knot of cord: grandmultiparity, chronic
      hypertension, hydramnios, patients who undergone genetic amniocentesis, male
      gender and cord problems (prolapse of cord and cord around the neck). The
      incidence of fetal distress and meconium stained amniotic fluid was significantly
      higher among patients with true knots of cord (7% versus 3.6%, P<0.001 and 22%
      versus 16%, respectively, P<0.0001). Moreover, there was a four-fold higher rate
      of antepartum fetal death among those fetuses (1.9% versus 0.5%, P<0.0001). In
      addition, fetuses with true knots of the umbilical cord were more often delivered
      by a cesarean section (130/841 versus 711/68,298, P<0.0001). The following
      obstetrical factors were found to be significantly correlated to true knots of
      the umbilical cord in a multiple logistic regression model: gestational diabetes,
      hydramnios, patients undergoing genetic amniocentesis, male fetuses. CONCLUSIONS:
      Patients with hydramnios, who underwent genetic amniocentesis and those carrying
      male fetuses are at an increased risk for having true knots of the umbilical
      cord. Thus, careful sonographic and Doppler examinations should be seriously
      performed in these patients for detection of the complication of the umbilical
      cord.

PMID- 11516798
TI  - The effect of dexamethasone on expression of mitogen-induced cyclooxygenase-2
      mRNA by amnion-derived (WISH) cells.
AB  - OBJECTIVES: It has been reported that prostaglandin E(2) (PGE(2)) is synthesized
      in the amnion and that this synthesis increases during labor. The purpose of this
      study was to clarify the mechanism for the expression of cyclooxygenase-2 (COX-2)
      mRNA and the PGE(2) synthesis of amnion-derived (WISH) cells. STUDY DESIGN: Cells
      were cultured and treated by 12-O-tetradecanoylphorbol-13-acetate (TPA) and
      dexamethasone (DEX). PGE(2) in the culture medium was measured by ELISA. Total
      RNA was extracted from the cells, and COX-2 mRNA expression was analyzed by
      Northern blot analysis. RESULTS: During the time course of PGE(2) production in
      response to TPA stimulation, the PGE(2) production could not be detected until
      incubation had continued for 2h, but this production appeared to continue after
      4h of incubation. PGE(2) production was significantly increased by TPA and
      suppressed by treatment with TPA and DEX. During the time course of COX-2 mRNA
      expression in response to treatment with TPA, the COX-2 mRNA band was detected
      after 1.5h. The strongest expression of COX-2 mRNA was observed at 2h incubation.
      After pre-treatment with TPA for 1h, the TPA-induced COX-2 mRNA was suppressed by
      treatment with DEX for 1 or 2h incubation in a dose-dependent manner.
      CONCLUSIONS: These results suggest that COX-2 mRNA is induced by TPA which
      activate protein kinase C, and suppressed by DEX in WISH cells.

PMID- 11516799
TI  - Changes in intrafollicular pressure in the rat ovary by nitric oxide and by
      alteration of systemic blood pressure.
AB  - BACKGROUND: ovulation is associated with degradation of the follicular apex
      vasodilatation and increased permeability of ovarian vessels. These changes may
      maintain or increase intrafollicular pressure (IFP) at ovulation to cause rupture
      of the follicular wall. OBJECTIVE: to investigate the possible regulation of IFP
      during the ovulatory process. STUDY DESIGN: immature Sprague-Dawley rats were
      primed with pregnant mare serum gonadotrophin (PMSG; 10IU) and given hCG (10IU)
      48h later. The ovary was exposed 48-60h after PMSG, micropipette inserted into
      the Graafian follicle and the IFP measured at three time periods: preovulatory
      (PO) 48h after PMSG; midovulatory (MO) 4-7h after hCG; late ovulatory (LO) 9-12h
      after hCG. The offset of the nitric oxide synthase (NOS) inhibitor L-arginine
      methyl ester (L-NAME), the alpha(1)-adrenoceptor agonist phenylephrine and the
      beta-adrenoceptor agonist isoprenaline were tested. RESULTS: phenylephrine given
      i.v. increased the systemic blood pressure, and significantly decreased the IFP
      in the LO phase (78% of pre-treatment value). Local administration of
      phenylephrine or isoprenaline (1ml of 1.5-15 microM) by superfusion over the
      ovary did not change the IFP. Local administration of L-NAME (1ml of 2 microM)
      significantly lowered (P<0.05) the IFP in the MO and LO phases, but was without
      effect in the PO phase. CONCLUSION: this study reveals that IFP regulation may be
      related to changes of the systemic blood pressure and that NO may be one local
      ovarian mediator in IFP regulation.

PMID- 11516800
TI  - Ovulation induction and risk of endometrial cancer: a pilot study.
AB  - OBJECTIVE: To determine whether women with endometrial carcinoma are more likely
      to have been exposed to fertility drugs, in particular clomiphene, than healthy
      population controls. STUDY DESIGN: A nationwide case-control, pilot study. About
      128 living women 35-64 years old, with a histologically confirmed diagnosis of
      endometrial carcinoma that was first diagnosed and reported to The Israel Cancer
      Registry between 1 January 1989 and 31 December 1992 were enrolled. The controls
      were 255 women from the same dialing areas selected by random digit dialing. A
      variety of demographic and clinical parameters were compared between cases and
      controls. A multivariate logistic model, controlling for age, was used to assess
      the independent effects of factors found to be significantly associated with
      endometrial cancer on univariate analysis. RESULTS: About 7 women with
      endometrial carcinoma (5.5%) and 10 healthy controls (3.9%) reported that they
      had used any fertility drug (crude odds ratio (OR) 1.4; 95% confidence interval
      (CI) 0.47-4.2). Use of fertility drugs did not meet the criteria for entry into
      the logistic model. The following parameters were found to be independently
      associated with endometrial cancer controlling for age, European-American
      background OR=2.2, (95% CI 1.3-3.7, P=0.004); nulliparity OR=2.7 (95% CI 1.1-6.5,
      P=0.03); history of infertility OR=1.8 (95% CI 1.0-3.3, P=0.05); BMI> or =27
      OR=2.3 (95% CI 1.4-3.9, P=0.001). The use of oral contraceptives and IUD were
      found to be protective, OR=0.29 and 0.37, respectively, (95% CI 0.14-0.61,
      P=0.001 and 0.19-0.70, P=0.003, respectively). CONCLUSIONS: We found no evidence
      that the use of ovulation induction agents, including clomiphene citrate, are
      associated with a higher risk of endometrial carcinoma. The association between
      infertility drugs and endometrial carcinoma should be examined in other, larger
      studies.

PMID- 11516801
TI  - Androgen, estrogen and progesterone receptor expression in the human uterus
      during the menstrual cycle.
AB  - Cyclic changes in steroid receptor expression in endometrial cells are considered
      a reflection of its differential functions. Besides estrogen and progestogens,
      androgens have also been suggested to affect the biological function of the
      female reproductive tract. We investigated the distribution and intensity of
      immuno-cytochemical estrogen receptor (ER), progesterone receptor (PR) and
      androgen receptor (AR) staining in the various cell types of human endometrium
      and myometrium during the different menstrual cycle phases in 30 paraffin
      embedded sections.AR expression in endometrial stromal cells decreased gradually
      from early proliferative till mid secretory phase. In the late secretory phase,
      AR expression in all cell types distinguished. Staining of epithelial cells was
      moderate. The disappearance of AR expression before cyclic separation of
      endometrial tissue may be causally related or just an epiphenomenon. Due to local
      competition for 5alpha-reduction of testosterone and the excess of progesterone
      in the secretory phase, the level of dihydrotestosterone (DHT) will be
      diminished. Hypothetically, if AR synthesis in endometrium would be DHT
      dependent, it would explain the lack of AR expression in the late secretory
      phase.

PMID- 11516802
TI  - Detection of interleukin-6, interleukin-8, and interleukin-11 in plasma from
      women with spontaneous abortion.
AB  - OBJECTIVE: To investigate the role of IL-6, IL-8, and IL-11 in the immune
      regulatory mechanisms involved in the spontaneous abortion of the first trimester
      of pregnancy. STUDY DESIGN: Plasma levels of IL-6, IL-8, and IL-11 were
      determined in 68 women who had a spontaneous abortion of unknown aetiology during
      the first trimester of pregnancy. They were compared with the corresponding
      levels of 73 age-matched pregnant women who had an uneventful pregnancy, and 52
      age-matched non-pregnant women. All enrolled women presented without any severe
      disease, syndrome or recent infection. Cytokine levels were measured by a
      sensitive sandwich enzyme-linked immunoassay. RESULTS: The women with spontaneous
      abortion had significantly decreased plasma levels of IL-6, IL-8 and IL-11
      compared to those with normal pregnancies (P<0.05). The non-pregnant women had no
      detectable cytokine levels. CONCLUSIONS: The reduced plasma levels of IL-6, IL-8
      and IL-11 in women with spontaneous abortion may be related to the underlying
      aetiopathogenetic mechanisms, however, there is no sufficient evidence for their
      use as predictive markers of pregnancy outcome.

PMID- 11516803
TI  - Assessment of the effectiveness of postmenopausal tibolone therapy on neural
      functions by measuring visual evoked potentials: a placebo-controlled study.
AB  - OBJECTIVE: To assess the effect of hormone replacement therapy on neural
      transmission in postmenopausal women using tibolone by a non-invasive, objective
      way. STUDY DESIGN: In a randomised, 3 cycle, placebo-controlled study,
      neurovisual transmission in optic pathways were evaluated by measuring visual
      evoked potentials (VEP). After neuroophtalmologic examination, eligible subjects
      were randomised into two groups. Treatment group (n=38) were given tibolone 2.5mg
      daily continuously for 3 months and control group (n=20) were treated with
      placebo. A baseline VEP measurement before the treatment and then at the end of
      first, second and third month were obtained by the EMG-evoked system in the
      Department of Neurology, University of Celal Bayar, Manisa, Turkey. RESULTS: Data
      from 31 women from treatment group and 16 from control group were available for
      evaluation. The mean P(100) latency values, which indicate the transition time
      period between the optic stimuli and electrical change recorded on the occipital
      area by the skin electrodes, have showed a significant decrease for the study
      group (from 100.39+/-0.58 to 97.90+/-0.65 ms, P<0.01) at the end of the first
      month of treatment according to the baseline values. This difference between two
      groups has remained constant during the study period. CONCLUSION: The change in
      latency measurements of VEP, reflecting the functional status in optic pathways
      from retina to occipital cortex were significantly different in the treatment
      group than in that of control. We concluded that a facilitating effect of
      tibolone was observed on neurovisual transmission.

PMID- 11516804
TI  - Laparoscopic hysterectomy in obese women: a clinical prospective study.
AB  - OBJECTIVE: To compare perioperative and postoperative outcomes of laparoscopic
      hysterectomy (LH) in surgical management of gynecological conditions in two
      groups of different weight. METHODS: A prospective comparative clinical study of
      271 LH performed for disease of female pelvic organs in a group of 54 obese
      patients (over 30 body mass index (BMI)) and in a group of 217 non-obese patients
      (less than 30 BMI). The following criteria were assessed: patient
      characteristics, indications for surgery, previous surgery, presence of
      adhesions, duration of procedure, blood loss, weight of specimen, hospital stay
      and complications. Statistical analysis was performed using the unpaired t-test
      and non-parametric Chi-square test when appropriate, with a significance level of
      P=0.05. RESULTS: Three non-obese patients were converted to laparotomy due to
      operative complications. Laparoscopy in the remaining 268 patients (98.89%) was
      completed successfully. There was no significant difference in estimated blood
      loss, presence and degree of adhesions, weight of specimen, length of hospital
      stay and postoperative complications between women with high BMI and those with
      low BMI. The rate of major operative complications (5.55% versus 3.22%) was
      higher in the obese group. The duration of the operation was longer in obese
      women. However, the significance of the difference was borderline (P=0.06).

PMID- 11516805
TI  - Patient satisfaction with management of ectopic pregnancy.
AB  - OBJECTIVES: This study was designed (1) to identify characteristics of patients
      and their treatment and aspects of care that may be associated with satisfaction,
      and (2) to investigate the way these factors contribute to the degree of
      satisfaction expressed after treatment of ectopic pregnancy. Our ultimate goal in
      so doing was to determine how to improve ectopic pregnancy management. STUDY
      DESIGN: We used data from a register of ectopic pregnancy established in an urban
      area (Communaute Urbaine de Lille) in northern France. Two months after ectopic
      pregnancy, a self-administered satisfaction questionnaire was completed by 192
      women treated between January 1995 and July 1996. We searched which factors were
      associated with satisfaction by a logistic regression model. RESULTS: Greater
      satisfaction was significantly associated with average education. Women were more
      satisfied when pregnancy was an expected event, and when fallopian tube was
      unruptured. Patients satisfied with the way they were received, the comfort, the
      willingness to listen and provide explanations, were more satisfied overall.
      Physical pain, anxiety for later fertility, and need of psychological support
      were associated with lesser degrees of satisfaction. When adjusted for these
      factors, the following factors remained significant: level of education;
      conditions of conception; pain; reception and willingness to listen. CONCLUSION:
      This study should increase awareness amongst health care professionals of the
      importance of a compassionate approach when dealing with patients following an
      ectopic pregnancy, since patients value this aspect of care.

PMID- 11516806
TI  - Adnexal torsion: a report on forty-five cases.
AB  - OBJECTIVES: To evaluate the clinical findings, evolution of treatment and ovarian
      function following conservative therapy. STUDY DESIGN: A case series of 45
      patients presenting with adnexal torsion between January 1989 and June 1999. All
      patients were surgically treated, either conservatively or radically. Patients
      who had received conservative treatment, interviewed by phone and underwent
      ovarian sonographic examination. RESULTS: Adnexal torsion is more frequent in
      young women with adnexal pathology. Conservative therapy by laparoscopy has
      gained increasing preference as a surgical procedure. It is safe and preserves
      ovarian function. CONCLUSIONS: Conservative therapy by laparoscopy is recommended
      to preserve ovarian function in young women.

PMID- 11516808
TI  - P53 overexpression predicts endometrial carcinoma recurrence better than HER
      2/neu overexpression.
AB  - OBJECTIVE: to investigate the prognostic value of p53 and HER-2/neu
      overexpression in endometrial cancer. STUDY DESIGN: p53 and HER-2/neu
      immunostaining was performed in 114 paraffin-embedded specimens of endometrial
      cancer diagnosed and treated between 1990 and 1997. Nuclear p53 and membrane HER
      2/neu immunostaining were used. RESULTS: p53 and HER-2/neu overexpression was
      observed in 17 cases (14.9%) and in 19 cases (16.7%), respectively. In univariate
      analysis p53 (P<0.001) and HER-2/neu (P=0.018) overexpression had a positive
      correlation with a high risk of recurrence. In multivariate analysis, age
      (P<0.001), FIGO stage (P<0.001), differentiation (P=0.013), non-endometrioid
      subtypes (P<0.001) and p53 overexpression (P<0.001), but not HER-2/neu
      overexpression, were independent prognostic indicators of recurrence.
      Simultaneous p53 and HER-2/neu overexpression made worse the prognostic
      (P<0.001). CONCLUSIONS: p53 overexpression was an independent predictor of
      recurrent disease in endometrial cancer. HER-2/neu overexpression had a more
      limited effect but enhance the effect of p53.

PMID- 11516807
TI  - Tolterodine reduces the number of urge incontinence episodes in patients with an
      overactive bladder.
AB  - OBJECTIVE: To evaluate the efficacy, safety and tolerability of tolterodine
      compared to placebo in patients with an overactive bladder. STUDY DESIGN: A
      double-blind, multi-centre phase III study in France and Belgium 251 patients
      with overactive bladder symptoms, and urodynamically verified detrusor
      overactivity, were randomised to receive 4-week treatment with either placebo or
      tolterodine 1 or 2mg twice daily (bd). Efficacy was evaluated from patient
      micturition diaries. Safety and tolerability endpoints were also evaluated.
      RESULTS: After 4-week treatment, the number of incontinence episodes/24h
      decreased significantly relative to placebo in the tolterodine 1 and 2 mgbd
      groups (P=0.045 and P=0.0089, respectively). Both dosages of tolterodine
      increased volume voided per micturition compared with placebo (P=0.055 and
      P=0.056, respectively), although significant decreases in micturition frequency
      were not apparent. Tolterodine was safe and well tolerated, few patients were
      withdrawn due to adverse events. Dry mouth, mainly of mild-to-moderate intensity,
      was the most common adverse event. No clinically relevant changes in blood
      pressure or laboratory safety variables were reported. CONCLUSION: Tolterodine is
      effective, safe and well tolerated for the treatment of symptoms of an overactive
      bladder, particularly urge incontinence.

PMID- 11516809
TI  - Mast cell distribution and density in the normal uterus--metachromatic staining
      using lectins.
AB  - This study investigates the number and the distribution of mast cells in the
      normal human uterus. Reliability of results was ensured by prompt tissue fixation
      and the use of biotin-labelled lectins in conjunction with the avidin-biotin
      peroxidase complex (ABC) method. This design revealed that mast cells are,
      indeed, normal constituents of the human uterus. They occur in large numbers in
      the myometrium, but are only scanty in the endometrium where they tend to be
      confined to the stratum basalis. The mean mast cell counts per high power field
      (MC/HPF), after staining with Canavalia ensiformis agglutinin (Con A), were
      17.9MC/HPF in the inner half of the myometrium, and 8.3MC/HPF in the outer half
      of the myometrium; 2.7MC/HPF in the basalis, and 0.3MC/HPF in the functionalis
      (P<0.05). There are no apparent differences in the number of mast cells between
      the normal proliferative and secretory phase endometrium, however, endometrial
      mast cells are considerably reduced and, apparently, depleted of metachromatic
      granules during the immediate pre-menstrual phase of the menstrual cycle. It is
      presumed that this, almost exclusive, presence of mast cells in the basal layer
      of the endometrial matrix, combined with the discharge of their cytoplasmic
      granules towards the end of the cycle, may be related with the contracting
      process preceding menstruation. On the other hand, the relative paucity of mast
      cells in the functional layer may contribute to the immune tolerance of the
      gestational endometrium to the implantation of the blastocyst.

PMID- 11516810
TI  - Immunohistochemical localization of aromatase and apoptosis-associated proteins
      in ovarian serous cystadenocarcinoma arising from ovarian endometriosis.
AB  - An immunohistochemical study was made of a case of serous cystadenocarcinoma that
      had been shown to have arisen from ovarian endometriosis. Aromatase cytochrome
      P450 (P450arom), an enzyme responsible for estrogen biosynthesis, was localized
      in the epithelial linings of the endometriosis and faintly in the transitional
      part, whereas it was not expressed in the carcinoma tissue. In contrast, estrogen
      receptors, progesterone receptors, and apoptosis-associated proteins, Fas, Fas
      ligand, and Bax were expressed in both endometriosis and carcinoma tissues of the
      tumor, whereas Bcl-2 was not expressed in either tissue of the tumor. It was
      suggested that the undifferentiated shift of the histologic grade might result in
      the loss of P450arom and that the malignant transformation was not caused by an
      altered balance of apoptosis-associated proteins. Accumulation of these studies
      may lead to a better understanding of the nature of malignant transformation of
      ovarian endometriosis.

PMID- 11516811
TI  - Ultrasonographic and morphological studies of the postmenopausal endometrium
      using unopposed estrogen replacement therapy with regular pause: a prospective
      preliminary study.
AB  - Hormone replacement therapy with progestogen is known to have severe side effects
      or complications in certain patients. OBJECTIVE: The goal of this study is to
      evaluate the safety and efficacy of an alternative treatment regimen with a
      mensal pause using both transvaginal sonography (TVS) and endometrial biopsy to
      follow patients. METHODS: A total of 30 postmenopausal women were treated with
      unopposed estrogen for 21 days each month followed by a regular pause of 9-10
      days, and were studied prospectively for 18 months. The TVS measurements of
      endometrial thickness and biopsy of the endometrium were done on the 21st day of
      treatment and the 7th day of the pause at 6-month intervals throughout the study.
      RESULTS: There was a significant decrease of proliferative activity at all three
      time points during the study (6, 12 and 18 months) when tested on the 7th pause
      day (PD7). The percentage of patients with hyperplasia without nuclear atypia and
      endometrial thickness > or =8mm was 32% at 6 months, but decreased to 22 and 19%
      at 12 and 18 months, respectively. All cases of hyperplasia regressed after the
      hormonal pause throughout the treatment period. CONCLUSIONS: This study presents
      an alternative treatment regimen for select patients having side effects or
      complications from progestogen administration; however, studies evaluating the
      safety and efficacy of this regimen over longer time periods are necessary.

PMID- 11516812
TI  - Ovarian strumal carcinoid tumor responsible for carcinoid heart disease.
AB  - We report a case of right ovarian strumal carcinoid tumor responsible for
      tricuspid regurgitation. Valve replacement and salpingo-oophorectomy were
      performed. Serotonin level and tomodensitometry were normal at 3-year follow-up.
      Rarity of strumal carcinoid tumor explains why this tumor has never been reported
      with carcinoid heart disease before.

PMID- 11516813
TI  - Labial delivery.
AB  - Paravaginal delivery is extremely rare. Perineal delivery was reported in just
      fewer than 100 cases, most of which occurred in the 19th and early 20th century.
      To our knowledge this is the first case of labial delivery to be reported. The
      baby delivered through a lateral vaginal tear and through the labia majora with
      little trauma to the underlying tissues. Explanations of how this could have
      happened and how to prevent it are discussed.

PMID- 11516814
TI  - Vascular endothelial growth factor levels in pleural and peritoneal fluid in
      Meigs' syndrome.
AB  - We report that we found differences in changes in vascular endothelial growth
      factor (VEGF) levels in pleural effusion and ascites after removal of ovarian
      tumor complicated by Meigs' syndrome. Postoperative VEGF levels decreased in the
      patient's pleural fluid but not in the peritoneal fluid. The mechanism of the
      development of the pleural effusion and ascites in Meigs' syndrome may differ.

PMID- 11516815
TI  - Broad ligament hematoma causing fetal death in a case of fracture pelvis.
AB  - Although motor ventricular accidents complicates 6-7% of all pregnancies, the
      experience of pelvic fractures in near term gravid patients is limited. We
      present a unique case of fetal death caused by bilateral broad ligament hematomas
      following maternal pelvic fracture which improved our understanding of management
      of such cases.

PMID- 11516816
TI  - Ureteric calculi masquerading metastatic lymph nodes in a case of endometrial
      cancer.
AB  - Extensive pelvic lymph node metastasis in the absence of risk factors was noticed
      at surgical staging for endometrial cancer in a 55-year-old postmenopausal women.
      On exploration there was a dilemma as to the disappearing lymph nodes which
      subsequently proved to be asymptomatic ureteric calculi. The need to palpate the
      pelvic side walls at the time of surgery for endometrial cancer even in cases
      when no nodal enlargement is detected preoperatively is highlighted.

PMID- 11516817
TI  - Monozygotic twins following blastocyst transfer: a report of two cases.
AB  - Several studies have shown an increased risk for monozygotic twinning after
      fertilization treatments. We present the clinical and sonographic characteristics
      of two monozygotic twin cases following blastocyst transfer. It is suggested that
      delayed transfer of the embryo in the blastocyst stage is a contributing factor
      to monozygotic twinning.

PMID- 11516819
TI  - Experience-dependent changes in cerebral functional connectivity during human
      rapid eye movement sleep.
AB  - One function of sleep is hypothesized to be the reprocessing and consolidation of
      memory traces (Smith, 1995; Gais et al., 2000; McGaugh, 2000; Stickgold et al.,
      2000). At the cellular level, neuronal reactivations during post-training sleep
      in animals have been observed in hippocampal (Wilson and McNaughton, 1994) and
      cortical (Amzica et al., 1997) neuronal populations. At the systems level, using
      positron emission tomography, we have recently shown that some brain areas
      reactivated during rapid-eye-movement sleep in human subjects previously trained
      on an implicit learning task (a serial reaction time task) (Maquet et al., 2000).
      These cortical reactivations, located in the left premotor area and bilateral
      cuneus, were thought to reflect the reprocessing--possibly the consolidation--of
      memory traces during post-training rapid-eye-movement sleep. Here, the experience
      dependent functional connectivity of these brain regions is examined. It is shown
      that the left premotor cortex is functionally more correlated with the left
      posterior parietal cortex and bilateral pre-supplementary motor area during rapid
      eye-movement sleep of subjects previously trained to the reaction time task
      compared to rapid-eye-movement sleep of untrained subjects. The increase in
      functional connectivity during post-training rapid-eye-movement sleep suggests
      that the brain areas reactivated during post-training rapid-eye-movement sleep
      participate in the optimization of the network that subtends subject's visuo
      motor response. The optimization of this visuo-motor network during sleep could
      explain the gain in performance observed during the following day.

PMID- 11516820
TI  - Nicotine-induced alterations in the expression of nicotinic receptors in primary
      cultures from human prenatal brain.
AB  - The nicotinic receptor proteins and gene transcripts for the different nicotinic
      receptor subunits exist in human prenatal brain already at 4-5 weeks of
      gestation. The early presence of nicotinic receptors suggests an important role
      for these receptors in modulating dendritic outgrowth, establishment of neuronal
      connections and synaptogenesis during development. When measurements of nicotinic
      receptors using [(3)H]epibatidine (labelling both the alpha3 and alpha4 subtype)
      and [(3)H]cytisine (labelling the alpha4 subtype) were performed in intact cells
      from the cortex, subcortical forebrain and mesencephalon (7.5-11 weeks of
      gestation), the highest specific binding for both ligands was detected in cells
      from mesencephalon, followed by subcortical forebrain and cortex. The effects of
      nicotine exposure were studied in primary cultures of prenatal brain (7.5-11
      weeks of gestation). Treatment with nicotine (1-100 microM) for 3 days
      significantly increased the specific binding of [(3)H]epibatidine and
      [(3)H]cytisine in cortical cells but not in cells from subcortical forebrain and
      mesencephalon brain regions, indicating region-specific differences in the
      sensitivity to nicotine exposure. Relative quantification of mRNA showed that the
      expression of the nicotinic receptor subunits alpha3 and alpha7, but not alpha4,
      was increased in cortical cells after nicotine treatment. These findings support
      the assumption of a potential risk of disturbance in the functional role of
      nicotinic receptors during brain development as a consequence of maternal smoking
      during pregnancy.

PMID- 11516821
TI  - A common profile of prefrontal cortical activation following exposure to nicotine
      or chocolate-associated contextual cues.
AB  - Conditioning and learning factors are likely to play key roles in the process of
      addiction and in relapse to drug use. In nicotine addiction, for example,
      contextual cues associated with smoking can be powerful determinants of craving
      and relapse, even after considerable periods of abstinence. Using the detection
      of the immediate-early gene product, Fos, we examined which regions of the brain
      are activated by environmental cues associated with nicotine administration, and
      compared this profile to the pattern induced by cues associated with a natural
      reward, chocolate. In the first experiment, rats were treated with either
      nicotine (0.4 mg/ml/kg) or saline once per day for 10 days in a test environment
      distinct from their home cages. In the second experiment, rats were given access
      to either a bowl of chocolate chips or an empty bowl in the distinct environment
      for 10 days. After a 4-day interval, rats were re-introduced to the environment
      where they previously received either nicotine treatment or chocolate access.
      Nicotine-associated sensory cues elicited marked and specific activation of Fos
      expression in prefrontal cortical and limbic regions. Moreover, exposure to cues
      associated with the natural reward, chocolate, induced a pattern of gene
      expression that showed many similarities with that elicited by drug cues,
      particularly in prefrontal regions. These observations support the hypothesis
      that addictive drugs induce long-term neuroadaptations in brain regions
      subserving normal learning and memory for motivationally salient stimuli.

PMID- 11516822
TI  - Age-related differences in neurosteroid potentiation of muscimol-stimulated 36Cl(
      ) flux following chronic ethanol treatment.
AB  - Alcoholism and alcohol abuse create costly social and economic problems in many
      nations. Recent studies indicate that alcohol exposure during adolescence may
      convey unique risks for subsequent neurocognitive deficits and problem drinking.
      Although GABA(A) receptor function is one of the principle neurochemical targets
      of ethanol action in the adult brain, little is known about the effects of
      alcohol on this system during adolescence. Adolescent (30-day-old) and adult (90
      day-old) male rats were intermittently exposed to ethanol for 1 month. At various
      times after the end of the exposure period, synaptoneurosomes were prepared from
      their cerebral cortices. GABA(A) receptor-mediated 36Cl(-) influx was measured in
      the absence and presence of the neurosteroid 3alpha,21-dihydroxy-5alpha-pregnan
      20-one (THDOC). In tissue from ethanol-exposed animals, sensitization to the
      potentiating effects of the neurosteroid was apparent 5 and 12 days after ethanol
      withdrawal. This sensitization was more apparent at the low concentrations of
      THDOC in animals pretreated with ethanol as adolescents. Sensitization to the
      potentiating effects of a neurosteroid is an enduring phenomenon, persistent long
      after the acute phase of ethanol withdrawal, and may be indicative of long-term
      changes in GABA(A) receptor function. Enhanced neurosteroid sensitization in
      animals pretreated as adolescents is consistent with the notion that adolescence
      is a period of unique sensitivity to the effects of ethanol. This uniqueness may
      now be extended to the chronic effects of ethanol.

PMID- 11516823
TI  - Parvalbumin and calbindin are differentially distributed within primary and
      secondary subregions of the mouse auditory forebrain.
AB  - The calcium binding proteins parvalbumin and calbindin are thought to
      differentially regulate physiological functions and often show complementary
      distributions in the CNS. Our goal was to determine parvalbumin and calbindin
      distributions in the different subdivisions of mouse auditory thalamus and
      auditory cortex. Following fixation, FVB mouse brains (postnatal days 38-80) were
      sectioned along coronal and horizontal planes, then processed for parvalbumin and
      calbindin immunohistochemistry (antibodies: parvalbumin pa-235, calbindin-d-28k
      cl-300). Strong complementary differences in calcium binding protein
      distributions were found in mouse auditory thalamus. The ventral division of the
      medial geniculate, which is the principal relay to primary auditory cortex,
      exhibited dense parvalbumin but weak calbindin immunoreactivity. In contrast,
      most of the 'secondary' auditory thalamic regions surrounding the ventral
      division showed strong calbindin and lighter parvalbumin levels. Thus, the mouse
      auditory thalamus is composed of a parvalbumin positive 'core' surrounded by a
      calbindin positive 'shell'. Parvalbumin immunoreactivity was also more prominent
      in the primary auditory cortex than in the secondary belt auditory cortex.
      Calbindin immunoreactivity in auditory cortex was less clearly divided along
      primary/secondary lines, especially in supragranular layers. However, within
      infragranular layers, there was heavier staining in belt areas than in primary
      auditory cortex. In auditory thalamus, parvalbumin labeling was largely confined
      to the neuropil, whereas calbindin labeling involved somata and neuropil. In
      auditory cortex, somata and neuropil were positive for both proteins.In summary,
      the calcium binding proteins parvalbumin and calbindin were found to be
      differentially distributed within the primary and non-primary regions of mouse
      auditory forebrain. These differences in protein distribution may contribute to
      the distinct types of physiological responses that occur in the primary vs. non
      primary areas.

PMID- 11516824
TI  - Involvement of the brain-derived neurotrophic factor/TrkB pathway in
      neuroprotecive effect of cyclosporin A in forebrain ischemia.
AB  - Recent studies have shown that cyclosporin A, a specific antagonist of
      calcineurin, a phosphatase, ameliorates neuronal cell death in the CA1 sector of
      the hippocampus after forebrain ischemia in animal models. The mechanism of this
      neuroprotective effect, however, has not yet been established. Brain-derived
      neurotrophic factor (BDNF), a member of the neurotrophins, is one of the potent
      survival and developmental factors whose expression is regulated by cyclic AMP
      response element-binding protein (CREB). Activation of CREB is dependent on its
      phosphorylation at Ser(133), and calcineurin has been reported to dephosphorylate
      CREB via protein phosphatase 1. Based on these observations, we attempted to
      investigate how cyclosporin A treatment would affect the changes of
      phosphorylated CREB (pCREB), BDNF and its receptor tyrosine kinase B (TrkB) after
      forebrain ischemia in rats. Phosphorylation of CREB was kept augmented throughout
      the time course examined in cyclosporin A-treated animals, while it ceased
      without cyclosporin A. Reverse transcription-polymerase chain reaction revealed
      prolonged maintenance of BDNF mRNA expression in the CA1 sector of cyclosporin A
      treated animals. The protein expression of BDNF and TrkB appeared to be up
      regulated in cyclosporin A-treated animals, whereas it was transiently up
      regulated but decreased to the marginal level of expression without cyclosporin
      A.From these results we suggest that cyclosporin A induces pCREB by an inhibition
      of calcineurin, resulting in the induction of BDNF. The mechanisms by which
      cyclosporin A protects the CA1 region from neuronal cell death in forebrain
      ischemia may involve the interaction of pCREB, BDNF and TrkB.

PMID- 11516825
TI  - Prolonged epileptiform bursting induced by 0-Mg(2+) in rat hippocampal slices
      depends on gap junctional coupling.
AB  - The transition from brief interictal to prolonged seizure, or 'ictal', activity
      is a crucial event in epilepsy. In vitro slice models can mimic many phenomena
      observed in the electroencephalogram of patients, including transition from
      interictal to ictaform or seizure-like activity. In field potential recordings,
      three discharge types can be distinguished: (1) primary discharges making up the
      typical interictal burst, (2) secondary bursts, lasting several hundred
      milliseconds, and (3) tertiary discharges lasting for seconds, constituting the
      ictal series of bursts. The roles of chemical synapses in these classes of burst
      have been explored in detail. Here we test the hypothesis that gap junctions are
      necessary for the generation of secondary bursts. In rat hippocampal slices,
      epileptiform activity was induced by exposure to 0-Mg(2+). Epileptiform
      discharges started in the CA3 subfield, and generally consisted of primary
      discharges followed by 4-13 secondary bursts. Three drugs that block gap
      junctions, halothane (5-10 mM), carbenoxolone (100 microM) and octanol (0.2-1.0
      mM), abolished the secondary discharges, but left the primary bursts intact. The
      gap junction opener trimethylamine (10 mM) reversibly induced secondary and
      tertiary discharges. None of these agents altered intrinsic or synaptic
      properties of CA3 pyramidal cells at the doses used. Surgically isolating the CA3
      subfield made secondary discharges disappear, and trimethylamine under these
      conditions was able to restore them.We conclude that gap junctions can contribute
      to the prolongation of epileptiform discharges.

PMID- 11516826
TI  - Upregulation of gap junction connexin 32 with epileptiform activity in the
      isolated mouse hippocampus.
AB  - Gap junctions, which serve as intercellular channels providing direct cytoplasmic
      continuity and ionic current flow between adjacent cells, are constituted by
      connexin proteins. Using an in vitro model of bicuculline-induced epileptiform
      activity, we asked whether increased connexin levels occur during epileptiform
      activity in the intact whole hippocampus, freshly isolated from young (15-day
      old) mouse brain. Exposure to bicuculline (10 microM), for 2-10 h, induced
      persistent changes in electrical activities that included enhanced spontaneous
      field activity (4 h), an epileptiform response to single electrical stimulation
      (6 h), and spontaneous epileptiform activity (6 h). These electrophysiological
      changes were not reversed by up to 60 min perfusion with normal artificial
      cerebrospinal fluid, but were greatly depressed by the gap junction uncoupler,
      carbenoxolone (120 microM, 10 min). Data from RNase protection assay and
      immunoblotting showed that among several detected gap junctions, only connexin 32
      was affected. After 2-6 h exposure to bicuculline, the connexin 32 mRNA
      expression was upregulated to 2-3-fold control (P < 0.01), and its protein level
      was significantly elevated the following 6 h (P < 0.01), at which time
      electrophysiologically measured evidence of clearly epileptiform activity was
      apparent. In addition, the transcription factor, c-fos protein, but not the cAMP
      response element-binding protein, was also found to be increased at the early
      stage of bicuculline exposure (2 h) compared to control (P < 0.05).Thus, we have
      found that exposing the acutely isolated hippocampus to bicuculline, induced
      increased c-fos protein, followed by increased connexin 32 transcript and
      protein, and concurrently, persistent epileptiform activity that was depressed by
      carbenoxolone.

PMID- 11516827
TI  - Biochemical and anatomical evidence for specialized voltage-dependent calcium
      channel gamma isoform expression in the epileptic and ataxic mouse, stargazer.
AB  - Inherited forms of ataxia and absence seizures in mice have been linked to
      defects in voltage-dependent calcium channel subunits. However, a correlation
      between the sites of neuronal dysfunction and the impact of the primary lesion
      upon calcium channel subunit expression or function has not been clearly
      established. For example, the mutation in stargazer mice has pleiotropic
      consequences including synaptic alterations in cerebellar granule cells,
      hippocampal CA3/mossy fibers, and cortical neurons in layer V that, presumably,
      lead to ataxia and seizures. Genetic analysis of stargazer mice determined that
      the defective gene encodes a protein expressed in brain (gamma2) with limited
      homology to the skeletal muscle L-type calcium channel gamma1 subunit. Although
      additional gamma isoforms have been subsequently identified primarily in neural
      tissue, little was known about the proteins they encode. Therefore, this study
      explored the distribution and biochemical properties of gamma2 and other gamma
      isoforms in wild-type and stargazer brain. We cloned human gamma2, gamma3, and
      gamma4 isoforms, produced specific anti-peptide antibodies to gamma isoforms and
      characterized both heterologously expressed and endogenous gamma. We identified
      regional specificity in the expression of gamma isoforms by western analysis and
      immunohistochemistry. We report for the first time that the mutation in the
      stargazer gene resulted in the loss of gamma2 protein. Furthermore, no
      compensatory changes in the expression of gamma3 or gamma4 protein were evident
      in stargazer brain. In contrast to other voltage-dependent calcium channel
      subunits, gamma immunostaining was striking in that it was primarily detected in
      regions highly enriched in excitatory glutamatergic synapses and faintly detected
      in cell bodies, suggesting a role for gamma in synaptic functions. Sites of known
      synaptic dysfunction in stargazer (the hippocampal CA3 region, dentate gyrus, and
      cerebellar molecular layer) were revealed as relying primarily upon gamma2, as
      total gamma isoform expression was dramatically decreased in these regions.
      Electron microscopy localized anti-gamma antibody immunostaining to dendritic
      structures of hippocampal mossy fiber synapses, with enrichment at postsynaptic
      densities. To assess the association of native gamma with voltage-dependent
      calcium channel or alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid
      (AMPA) receptor subunits, gamma isoforms (gamma2, gamma3 and gamma4) were
      detergent solubilized from mouse forebrain. Antibodies against a highly conserved
      C-terminal epitope present in gamma2, gamma3 and gamma4 immunoprecipitated
      voltage-dependent calcium channel subunits (alpha1B), providing the first in vivo
      evidence that gamma and voltage-dependent calcium channels form stable complexes.
      Furthermore, both anti-gamma2 antibodies and anti-alpha1B antibodies
      independently immunoprecipitated the AMPA receptor subunit, GluR1, from mouse
      forebrain homogenates. In summary, loss of gamma2 immunoreactivity in stargazer
      is precisely localized so as to contribute to previously characterized synaptic
      defects. The data in this paper provide compelling evidence that gamma isoforms
      form complexes in vivo with voltage-dependent calcium channels as well as AMPA
      receptors, are selectively and differentially expressed in neuronal processes,
      and localize primarily to dendritic structures in the hippocampal mossy fiber
      region.

PMID- 11516828
TI  - Dentate hilar mossy cells and somatostatin-containing neurons are immunoreactive
      for the alpha8 integrin subunit: characterization in normal and kainic acid
      treated rats.
AB  - Integrins are heterodimeric cell surface receptors composed of different alpha
      and beta subunits that mediate cell-cell and cell-extracellular matrix
      interactions. They have been implicated in the regulation of neuronal migration,
      differentiation, process outgrowth, and plasticity. The alpha8 integrin subunit
      associates exclusively with the beta1 subunit to form a receptor (alpha8beta1)
      for fibronectin, vitronectin, tenascin, and osteopontin. In a previous study, we
      demonstrated that hippocampal dentate hilar neurons are immunoreactive for
      alpha8. The present study identifies the major types of alpha8-immunoreactive
      hilar neurons and characterizes the effects of kainic acid-induced seizures on
      alpha8-immunoreactivity in these cells. Examination of the hilus in normal rats
      revealed alpha8-immunoreactivity in the somatodendritic compartments of large
      hilar neurons identified as mossy cells, including a subset of dendritic thorny
      excrescences that were contacted by large mossy fiber terminals. alpha8
      immunoreactivity also was found in approximately 71% of somatostatin-containing
      hilar cells. Kainic acid-induced seizures dramatically and rapidly altered the
      levels and distribution of alpha8-immunoreactivity in hilar neurons. After 1.5 h
      of seizures, alpha8-immunoreactivity in their dendrites was reduced greatly. One
      day after kainic acid treatment, labeling was diminished throughout the
      somatodendritic compartments of most hilar cells. This decrease appeared to be
      transient, since alpha8 labeling returned to normal levels in surviving hilar
      neurons within 2 weeks of treatment. In addition, many alpha8-immunoreactive
      hilar neurons, particularly in caudal dentate regions, were lost 3-5 weeks after
      kainic acid treatment. Our findings suggest that alpha8beta1 may mediate adhesive
      interactions of the dendritic processes of mossy cells and somatostatin
      containing hilar neurons with other cellular elements or with extracellular
      matrix components. They also suggest that alpha8 may be susceptible to activity
      dependent proteolysis that could modulate its function in the somatodendritic
      compartment of these cells.

PMID- 11516829
TI  - Constitutive Cdc25B tyrosine phosphatase activity in adult brain neurons with M
      phase-type alterations in Alzheimer's disease.
AB  - The Cdc2/cyclin B kinase is a critical regulator of mitosis that is normally
      absent from terminally differentiated neurons of adult brain. However,
      unscheduled expression and activation of Cdc2/cyclin B has been seen in neurons
      undergoing degeneration in Alzheimer's disease. The presence of this mitotic
      kinase correlates with accumulation of mitotic phosphoepitopes in protein
      components of the hallmark neurofibrillary tangles. Of importance to the
      pathogenic mechanism of Alzheimer's disease is the striking appearance of
      Cdc2/cyclin B and mitotic phosphoepitopes prior to neurofibrillary tangle
      formation, which has suggested that a misappropriate mitotic cascade initiates
      and mediates the neurodegenerative process. To explain the atypical activation of
      Cdc2/cyclin B in degenerating neurons we have investigated the enzyme responsible
      for Cdc2/cyclin B activation in mitotic cells, i.e. the Cdc25B tyrosine
      phosphatase, in Alzheimer's disease brain. Although the enzyme appeared abundant
      in affected neurons, it was also evident in unaffected neurons of Alzheimer's
      disease and control brain. Thus, we have found, surprisingly, that Cdc25B is a
      normal constituent of adult brain neurons, with detectable basal levels of
      activity. In Alzheimer's disease the levels and activity of the enzyme are
      elevated, and the active enzyme predominates in the cytoplasmic compartment of
      neurons. Consistent with these M phase-type changes, Cdc25B displays increased
      immunoreactivity towards the MPM-2 mitotic phosphoepitope antibody. We propose
      that aberrant expression of Cdc2/cyclin B in Alzheimer's disease leads to
      potentiation of mitotic activation mediated by constitutive neuronal Cdc25B
      activity. As a result, various downstream indices of mitotic events are
      generated, eventually culminating in neurodegeneration. Our data also suggest
      that Cdc25B is functional in normal post-mitotic neurons lacking the mitotic
      Cdc2/cyclin B, but it does not appear to influence the activity of Cdk5, a Cdc2
      like kinase that is particularly enriched in brain.

PMID- 11516830
TI  - Regulation of apolipoprotein E secretion in rat primary hippocampal astrocyte
      cultures.
AB  - Apolipoprotein E isoforms may have differential effects on a number of
      pathological processes underlying Alzheimer's disease. Recent studies suggest
      that the amount, rather than the type, of apolipoprotein E may also be an
      important determinant for Alzheimer's disease. Therefore, understanding the
      regulated synthesis of apolipoprotein E is important for determining its role in
      Alzheimer's disease. We show here that in rat primary hippocampal astrocyte
      cultures, dibutyryl-cAMP increased apolipoprotein E secretion with time in a dose
      dependent manner (to 177% at 48 h) and that retinoic acid potentiated this effect
      (to 298% at 48 h). Dibutyryl-cAMP also gave a rapid, albeit transient, increase
      of apolipoprotein E mRNA expression (to 200% at 1 h). In contrast, the protein
      kinase C activator phorbol 12-myristate 13-acetate decreased both apolipoprotein
      E secretion (to 59% at 48 h) and mRNA expression (to 22% at 1 h). Phorbol 12
      myristate 13-acetate also reversed the effects of dibutyryl-cAMP. Apolipoprotein
      E secretion was also modulated by receptor agonists for the adenylyl cyclase/cAMP
      pathway. Isoproterenol (50 nM, a beta-adrenoceptor agonist) enhanced, while
      clonidine (250 nM, an alpha2-adrenoceptor agonist) decreased, secreted
      apolipoprotein E. We also analysed the effects of agonists for the phospholipase
      C/protein kinase C pathway. Arterenol (1 microM, an alpha1-adrenoceptor agonist)
      and serotonin (2.5 microM) enhanced, whereas carbachol (10 microM, an
      acetylcholine muscarinic receptor agonist) decreased secreted apolipoprotein E.
      The effects of these non-selective receptor agonists were modest, probably due to
      effects on different signalling pathways. Arterenol also potentiated the
      isoproterenol-mediated increase. We also show that phorbol 12-myristate 13
      acetate and dibutyryl-cAMP have opposite effects on nerve growth factor, as
      compared to apolipoprotein E, secretion, suggesting that the results obtained
      were unlikely to be due to a general effect on protein synthesis. We conclude
      that astrocyte apolipoprotein E production can be regulated by factors that
      affect cAMP intracellular concentration or activate protein kinase C. Alterations
      in these signalling pathways in Alzheimer's disease brain may have consequences
      for apolipoprotein E secretion in this disorder.

PMID- 11516831
TI  - Huperzine A, a nootropic alkaloid, inhibits N-methyl-D-aspartate-induced current
      in rat dissociated hippocampal neurons.
AB  - Huperzine A, a nootropic alkaloid isolated from a Chinese herb, has been proposed
      as one of the most promising agents to treat Alzheimer's disease. Recently, the
      agent was found to inhibit the N-methyl-D-aspartate (NMDA) receptors in rat
      cerebral cortex in addition to causing an inhibitory effect on
      acetylcholinesterase. In the present study, the mechanisms underlying NMDA
      receptor inhibition were investigated using whole-cell voltage-clamp recording in
      CA1 pyramidal neurons acutely dissociated from rat hippocampus. Huperzine A
      reversibly inhibited the NMDA-induced current (IC(50)=126 microM, Hill
      coefficient=0.92), whereas it had no effect on the current induced by alpha-amino
      3-hydroxy-5-methyl-4-isoxazole propionate or kainate. The effect was non
      competitive, and showed neither 'voltage-dependency', nor 'use-dependency'. The
      IC(50) values of huperzine A were neither altered by changing the concentrations
      of glycine (2-0.2 microM) and pH (7.4-6.7) in the external solution, nor by
      addition of Zn(2+) (5 microM) and dithiothreitol (5 mM) to the external solution.
      However, addition of spermine (200 microM) to the external solution caused a
      parallel shift to the right of the huperzine A concentration-response curve. From
      these we suggest that huperzine A acts as a non-competitive antagonist of the
      NMDA receptors, via a competitive interaction with one of the polyamine binding
      sites. The potential relevance of NMDA receptor antagonist activity of huperzine
      A to the treatment of Alzheimer's disease is discussed.

PMID- 11516832
TI  - Neonatal dopamine depletion reveals a synergistic mechanism of mRNA regulation
      that is mediated by dopamine(D1) and serotonin(2) receptors and is targeted to
      tachykinin neurons of the dorsomedial striatum.
AB  - It has been hypothesized that dopamine(D1) and serotonin(2) receptors become
      sensitized to agonist-mediated regulation of gene expression following loss of
      dopaminergic innervation to the striatum. We have previously demonstrated that
      the combined administration of dopamine(D1) and serotonin(2) receptor agonists to
      dopamine-depleted adult rats induced preprotachykinin mRNA expression within the
      periventricular rostral striatum to levels which were significantly different
      than what could be elicited by either agonist alone. In the present study, we
      have determined that this phenomenon is revealed only after dopamine depletion.
      In addition, it is targeted primarily to tachykinin producing neurons of the
      dorsomedial striatum and is dependent on both dopamine(D1) and serotonin(2)
      receptor activation. Preprotachykinin mRNA levels in the intact striatum were
      unaltered 4 h following an i.p. injection of either SKF-38393 (1 mg/kg,
      dopamine(D1) partial agonist) or (+/-)-1-(4-Iodo-2,5-dimethoxyphenyl)-2
      aminopropane (DOI 1 mg/kg, serotonin(2) agonist). However, the combined
      application of both agonists increased (+44%) preprotachykinin message levels,
      but these changes were restricted to the dorsomedial striatum. In adult animals
      depleted of dopamine as neonates, striatal preprotachykinin mRNA expression was
      reduced by approximately 50%. From this lowered level of basal expression, DOI or
      SKF-38393 raised preprotachykinin mRNA levels within the dorsomedial, but not the
      dorsolateral striatum. Furthermore, co-stimulation of dopamine(D1) and
      serotonin(2) receptors produced a nearly four-fold induction of preprotachykinin
      message levels in the dorsomedial striatum that was significantly greater than
      either agonist alone. Application of both agonists also elevated preprotachykinin
      mRNA expression within the dorsolateral striatum, but to a lesser extent. All
      increases in preprotachykinin mRNA resulting from co-application of SKF-38393 and
      DOI were prevented by pretreatment with either SCH-23390 (1 mg/kg, dopamine(D1)
      antagonist) or ritanserin (1 mg/kg, serotonin(2) antagonist). Alternately,
      preproenkephalin mRNA expression was unaffected by dopamine(D1) receptor
      stimulation, but was slightly elevated by DOI or both agonists together (42-58%)
      in intact animals. However, neither agonist treatment in this experiment
      significantly altered preproenkephalin mRNA expression in the dopamine-depleted
      striatum which was elevated in response to dopamine lesion alone. Dopamine
      depletion appears to promote a synergistic interaction between dopamine(D1) and
      serotonin(2) receptors that leads to enhanced expression of striatal
      preprotachykinin mRNA levels. The localization of this phenomenon to tachykinin
      neurons of the direct striatonigral pathway specifically within the dorsomedial
      regions of the rostral striatum may be relevant to the problem of dyskinetic
      behaviors which arise during the pharmacological treatment of movement disorders.

PMID- 11516833
TI  - Colocalization of calcium-binding proteins and GABA in neurons of the rat
      basolateral amygdala.
AB  - The basolateral amygdala contains subpopulations of non-pyramidal neurons that
      express the calcium-binding proteins parvalbumin, calbindin-D28k (calbindin) or
      calretinin. Although little is known about the exact functions of these proteins,
      they have provided useful markers of specific neuronal subpopulations in studies
      of the neuronal circuitry of the cerebral cortex and other brain regions. The
      purpose of the present study was to investigate whether basolateral amygdalar non
      pyramidal neurons containing parvalbumin, calbindin, or calretinin exhibit
      immunoreactivity for GABA, and to determine if calretinin is colocalized with
      parvalbumin or calbindin in the rat basolateral amygdala. Pyramidal neurons were
      distinguished from non-pyramidal neurons on the basis of staining intensity.
      Using immunofluorescence confocal laser scanning microscopy, as well as the
      'mirror technique' on immunoperoxidase-stained sections, it was found that there
      was virtually no colocalization of calretinin with parvalbumin or calbindin, but
      that the great majority of basolateral amygdalar non-pyramidal neurons containing
      parvalbumin, calbindin, or calretinin exhibited GABA immunoreactivity. Calbindin
      positive neurons constituted almost 60% of the GABA-containing population in both
      subdivisions of the basolateral nucleus and more than 40% of the GABA-containing
      population in the lateral nucleus. Parvalbumin-positive neurons constituted 19
      43% of GABA-immunoreactive neurons in the basolateral amygdala, depending on the
      nucleus. Calretinin-positive non-pyramidal neurons constituted about 20% of the
      GABA-positive neuronal population in each nucleus of the basolateral amygdala.
      These findings indicate that non-pyramidal neurons containing parvalbumin,
      calbindin, or calretinin comprise the majority of GABA-containing neurons in the
      basolateral amygdala, and that the calretinin subpopulation is distinct from non
      pyramidal subpopulations containing parvalbumin and calbindin. These separate
      neuronal populations may play unique roles in the inhibitory circuitry of the
      amygdala.

PMID- 11516834
TI  - The main olfactory system mediates pheromone-induced fos expression in the
      extended amygdala and preoptic area of the male Syrian hamster.
AB  - Copulation in male hamsters is stimulated by exposure to vaginal secretions of
      conspecifics. These pheromones also stimulate fos expression in neural areas that
      regulate copulation including: the medial nucleus of the amygdala, the bed
      nucleus of the stria terminalis, and the preoptic area. The pheromones in vaginal
      secretions are detected by both the main and accessory olfactory systems.
      However, the accessory system plays the greater role in the regulation of mating
      behavior and has direct connections with the medial nucleus of the amygdala and
      bed nucleus of the stria terminalis. The goal of the present study was to
      determine which system mediates the effect of pheromones on the stimulation of
      more central areas by deafferenting these systems in experienced male hamsters
      before exposure to vaginal secretions. Destruction of the receptors in the main
      olfactory system with zinc sulfate eliminated the increase in fos
      immunoreactivity in the amygdala, bed nucleus of the stria terminalis and
      preoptic area following exposure to sexually stimulating pheromones.
      Deafferentation of the accessory olfactory system by removing the vomeronasal
      organ had no effect on pheromone-induced fos expression in these areas. We
      conclude that neurons expressing fos following exposure to vaginal secretions are
      stimulated via the main olfactory system and are not associated with the
      expression of copulatory behavior.

PMID- 11516835
TI  - Medullary neurones regulate hypothalamic corticotropin-releasing factor cell
      responses to an emotional stressor.
AB  - Hypothalamic-pituitary-adrenal axis activation is a hallmark of the stress
      response. In the case of physical stressors, there is considerable evidence that
      medullary catecholamine neurones are critical to the activation of the
      paraventricular nucleus corticotropin-releasing factor cells that constitute the
      apex of the hypothalamic-pituitary-adrenal axis. In contrast, it has been thought
      that hypothalamic-pituitary-adrenal axis responses to emotional stressors do not
      involve brainstem neurones. To investigate this issue we have mapped patterns of
      restraint-induced neuronal c-fos expression in intact animals and in animals
      prepared with either paraventricular nucleus-directed injections of a retrograde
      tracer, lesions of paraventricular nucleus catecholamine terminals, or lesions of
      the medulla corresponding to the A1 or A2 noradrenergic cell groups. Restraint
      induced patterns of neuronal activation within the medulla of intact animals were
      very similar to those previously reported in response to physical stressors,
      including the fact that most stressor-responsive, paraventricular nucleus
      projecting cells were certainly catecholaminergic and probably noradrenergic.
      Despite this, the destruction of paraventricular nucleus catecholamine terminals
      with 6-hydroxydopamine did not alter corticotropin-releasing factor cell
      responses to restraint. However, animals with ibotenic acid lesions encompassing
      either the A1 or A2 noradrenergic cell groups displayed significantly suppressed
      corticotropin-releasing factor cell responses to restraint. Notably, these
      medullary lesions also suppressed neuronal responses in the medial amygdala, an
      area that is now considered critical to hypothalamic-pituitary-adrenal axis
      responses to emotional stressors and that is also known to display a significant
      increase in noradrenaline turnover during restraint. We conclude that medullary
      neurones influence corticotropin-releasing factor cell responses to emotional
      stressors via a multisynaptic pathway that may involve a noradrenergic input to
      the medial amygdala. These results overturn the idea that hypothalamic-pituitary
      adrenal axis response to emotional stressors can occur independently of the
      brainstem.

PMID- 11516836
TI  - In vivo observation of a non-noradrenergic regulation of arylalkylamine N
      acetyltransferase gene expression in the rat pineal complex.
AB  - The rodent pineal gland is the end point of several peripheral and central fibers
      innervating the superficial and deep parts of the gland. Up to now, only the
      sympathetic transmitter norepinephrine is thought to regulate melatonin
      synthesis, although numerous biochemical experiments have reported in vitro
      effects of various transmitters on melatonin synthesis. To find out whether there
      is non-noradrenergic regulation of in vivo pineal metabolism, the mRNA encoding
      the enzyme arylalkylamine N-acetyltransferase was studied using the highly
      sensitive technique of in situ hybridization. The existence of a marked nocturnal
      increase of arylalkylamine N-acetyltransferase mRNA in the superficial pineal
      gland was confirmed. Interestingly and for the first time, a similar daily
      variation was observed in the deep pineal. After removal of superior cervical
      ganglia, the daily rhythm in arylalkylamine N-acetyltransferase mRNA was
      abolished in both the superficial and deep pineal indicating that the rhythm is
      driven by sympathetic input in the entire pineal complex. Interestingly, the
      remaining arylalkylamine N-acetyltransferase mRNA level in the pineal of day- and
      night-time ganglionectomized rats was significantly higher than in the pineal of
      day-time intact animals. These data reveal a sympathetic-dependent day-time
      inhibition of arylalkylamine N-acetyltransferase gene expression. In addition,
      the day-time pineal arylalkylamine N-acetyltransferase mRNA expression in
      ganglionectomized rats persisted after adrenal gland removal but was reduced by
      50% after propranolol injection. These results indicate that arylalkylamine N
      acetyltransferase mRNA in ganglionectomized rats is not induced by circulating
      catecholamines and may be caused by both a centrally originated norepinephrine,
      as already suggested, and other non-adrenergic transmitter(s). In conclusion,
      this work shows that norepinephrine drives the nocturnal increase of
      arylalkylamine N-acetyltransferase gene expression both in the superficial and
      deep pineal and strongly suggests that other neurotransmitters are involved in
      day-time inhibition and night-time stimulation of pineal metabolism.

PMID- 11516837
TI  - Modulation of Purkinje cell response to glutamate during the sleep-waking cycle.
AB  - The hypothesis that corticocerebellar responsiveness is modified by the
      behavioral state was tested in freely moving rats by evaluating the responses of
      extracellularly recorded Purkinje cells located in the cerebellar posterior
      vermis to microiontophoretically applied glutamate (8-80 nA for 3-5 s every 30-32
      s) during the spontaneous sleep-waking cycle. Rats were chronically implanted for
      polygraphic recordings so that responses of Purkinje cells to glutamate could be
      related to the states of quiet waking, slow-wave sleep and paradoxical sleep.
      Analysis on a population of 33 neurons subjected to alternate periods of sleep
      and waking showed that the mean response to glutamate was significantly reduced
      to 75+/-18% during slow-wave sleep with respect to waking. This effect occurred
      independently on changes of basal firing rate which in sleep was slightly,
      although significantly, reduced to 94+/-12%. Independence of glutamate response
      modulation from changes of baseline firing was also observed in a different data
      set obtained from 19 Purkinje cells which were recorded during a continuous slow
      wave sleep period that allowed several consecutive drug applications. In this
      condition responses to glutamate progressively decreased as sleep proceeded while
      spontaneous activity remained stable after a slight decrease at the transition
      from waking to sleep. Spectral analysis performed on the electroencephalogram
      signal, in particular on epochs centered around each glutamate pulse, revealed
      that for both data sets the reduction of neuronal responsiveness was related to
      the intensity of slow-wave sleep and more precisely to the delta and slow
      oscillation (0.6-4.2 Hz) content of the power spectrum of the
      electroencephalogram. Spontaneous and glutamate-evoked activity were also
      evaluated in 23 Purkinje cells during transition from slow-wave sleep to
      paradoxical sleep. In particular, during paradoxical sleep spontaneous activity
      became irregular so that for 44 out of 90 glutamate responses quantification was
      unreliable. The remaining 46 responses were characterized by high variability in
      amplitude even within the same episode of paradoxical sleep. With respect to the
      preceding slow-wave sleep values, 17/46 responses increased, 14/46 decreased and
      15/46 remained within the 15% limit, giving a mean value of 132%. These data
      indicate that Purkinje cell response to glutamate is modulated during the
      spontaneous sleep-waking cycle. We speculate that this modulation depends upon
      the action of the neuromodulatory systems which diffusely project to the
      cerebellum, whose function would be to adapt the performance of the cerebellar
      circuits to changes of the animal state. On the other hand, the phasic changes in
      amplitude of Purkinje cell response during paradoxical sleep could be due to the
      interaction between the effects of glutamate application and those exerted by
      endogenous signals possibly related to the phasic events of this sleep stage.

PMID- 11516838
TI  - trkA modulation of developing somatosensory neurons in oro-facial tissues: tooth
      pulp fibers are absent in trkA knockout mice.
AB  - To investigate the nerve growth factor requirement of developing oro-facial
      somatosensory afferents, we have studied the survival of sensory fibers
      subserving nociception, mechanoreception or proprioception in receptor tyrosine
      kinase (trkA) knockout mice using immunohistochemistry. trkA receptor null mutant
      mice lack nerve fibers in tooth pulp, including sympathetic fibers, and showed
      only sparse innervation of the periodontal ligament. Ruffini endings were formed
      definitively in the periodontal ligament of the trkA knockout mice, although
      calcitonin gene-related peptide- and substance P-immunoreactive fibers were
      reduced in number or had disappeared completely. trkA gene deletion had also no
      obvious effect on the formation of Meissner corpuscles in the palate. In the
      vibrissal follicle, however, some mechanoreceptive afferents were sensitive for
      trkA gene deletion, confirming a previous report [Fundin et al. (1997) Dev. Biol.
      190, 94-116]. Moreover, calretinin-positive fibers innervating longitudinal
      lanceolate endings were completely lost in trkA knockout mice, as were the
      calretinin-containing parent cells in the trigeminal ganglion.These results
      indicate that trkA is indispensable for developing nociceptive neurons
      innervating oral tissues, but not for developing mechanoreceptive neurons
      innervating oral tissues (Ruffini endings and Meissner corpuscles), and that
      calretinin-containing, trkA dependent neurons in the trigeminal ganglion normally
      participate in mechanoreception through longitudinal lanceolate endings of the
      vibrissal follicle.

PMID- 11516839
TI  - Anterograde and retrograde transport of active extracellular signal-related
      kinase 1 (ERK1) in the ligated rat sciatic nerve.
AB  - Neurons are one of the most polarized cells and often the nerve terminals may be
      located long distances from the cell body, thus signal transduction in neurons
      unlike other cells may need to be conducted over large distances. The mitogen
      activated protein/extracellular signal-regulated kinases (MAP kinases or ERKs)
      regulate a diverse array of functions and in neurons, the ERK signalling pathways
      appear to have an important role in activity-dependent regulation of neuronal
      function. Using the ligated rat sciatic nerve as an experimental model we
      previously showed that the ERK1/2, MAP/ERK kinase (MEK1/2) and the p110 catalytic
      subunit of PI3-kinase are transported in the rat sciatic nerve. We have extended
      these findings to determine if these proteins are transported in the active state
      using antibodies that specifically detect the active form of ERK1/2, MEK1/2 and
      AKT which is activated downstream of PI3-kinase. We show significant accumulation
      of active ERK1 on the proximal and distal sides of a nerve ligation after 16 h.
      Active ERK2 also appeared to be accumulating at the ligature, however this did
      not reach statistical significance. In contrast there was not any significant
      accumulation of active MEK1/2 or active AKT. A component of both active ERK1 and
      active ERK2 is present in between the two ligations suggesting they are also
      present in the surrounding Schwann cells and are activated in response to nerve
      injury. Taken together our results suggest that a component of the accumulation
      of active ERK1 on the distal and proximal side of the nerve ligations results
      from transport in the anterograde and retrograde direction in the rat sciatic
      nerve.

PMID- 11516840
TI  - Decreases in endomorphin-2-like immunoreactivity concomitant with chronic pain
      after nerve injury.
AB  - Nerve injury often leads to chronic, sometimes excruciating, pain. The mechanisms
      contributing to this syndrome include neurochemical plasticity in neurons
      involved in the earliest stages of pain transmission. Endomorphin-2 (Tyr-Pro-Phe
      Phe-NH(2)) is an endogenous morphine-like substance that binds to the mu-opioid
      receptor with high affinity and selectivity. Endomorphin-2-like immunoreactivity
      (LI) is present in the superficial layers of the dorsal horn in the spinal cord
      and in primary afferents, suggesting a role for this peptide in pain
      transmission. To determine whether spinal endomorphin-2-LI is altered in an
      animal model of chronic pain, the left sciatic nerve of Swiss Webster and ICR
      mice was ligated in a modified Seltzer model of nerve injury. Changes in
      endomorphin-2-LI were assessed by immunocytochemistry at 2, 4 and 14 days after
      nerve injury. The side of the spinal cord ipsilateral to the nerve injury
      exhibited a dramatic decrease in endomorphin-2-LI relative to the contralateral
      side and to control animals. The change was restricted to the medial dorsal horn
      in the lumbar segments innervated by the sciatic nerve. Substance P-LI showed a
      small decrease, while calcitonin gene-related peptide-LI was unchanged. Both
      thermal hyperalgesia, as evidenced by significantly decreased paw withdrawal
      latencies, and decreased endomorphin-2-LI were observed within 2 days of injury
      and were most pronounced at 2 weeks after injury. The decrease in endomorphin-2
      LI during the development of chronic pain is consistent with the loss of an
      inhibitory influence on pain transmission. These results provide the first
      evidence that reduction of an endogenous opioid in primary afferents is
      associated with injury-induced chronic pain.

PMID- 11516841
TI  - Expression of Schwann cell-specific proteins and low-molecular-weight
      neurofilament protein during regeneration of sciatic nerve treated with
      neurotrophin-4.
AB  - Neurotrophin-4 acts as a potent survival factor for subpopulations of
      motoneurons. To investigate its effect on Schwann cell sheath and axonal proteins
      during peripheral nerve regeneration, sciatic nerves in adult rats were
      transected and repaired, and fibrin glue containing neurotrophin-4 injected
      around the repair site. At 5, 15, 30 and 60 days after repair, 5-mm nerve
      segments distal to the repair were collected, and western blotting was used to
      measure myelin-associated glycoprotein, myelin basic protein and low-molecular
      weight neurofilament protein. In control groups these dramatically declined at 5
      and 15 days then increased from 30 and 60 days. However, in the neurotrophin-4
      group there was a significant increase (to several times basal values) in myelin
      associated glycoprotein and myelin basic protein at 5-15 days. The relatively
      small increases (<7%) in Schwann cell numbers suggest that this is mainly due to
      increased synthesis per cell. The neurotrophin-4 group also showed a small but
      significant increase at 15 days in low-molecular-weight neurofilament protein,
      which however remained much lower than basal. We conclude that neurotrophin-4
      regulates the expression of myelin-associated glycoprotein, myelin basic protein,
      and to a lesser extent low-molecular-weight neurofilament protein, during
      peripheral nerve regeneration.

PMID- 11516842
TI  - Bradykinin activates airway parasympathetic ganglion neurons by inhibiting M
      currents.
AB  - The action of bradykinin on neurons acutely isolated from airway parasympathetic
      ganglia of rats and its mechanism were investigated using the nystatin-perforated
      patch-clamp recording technique. Under current clamp conditions, an application
      of 0.1 microM bradykinin onto rat airway ganglion neurons induced a
      depolarization which was accompanied by the action potential firing. Bradykinin
      elicited inward currents with decreasing the membrane conductance when a ganglion
      neuron was held at a holding potential of -40 mV. The half-maximum effective
      concentration was 8.9 nM. The bradykinin response was mimicked by a B(2) receptor
      agonist, [Hyp(3)]-bradykinin, and was inhibited by HOE-140, a B(2) antagonist,
      suggesting the contribution of B(2) receptors. The bradykinin-induced inward
      current reversed at the K(+) equilibrium potential, which shifted 56.5 mV with a
      10-fold change in extracellular K(+) concentration. The application of 10(-3) M
      Ba(2+) induced the inward current, and bradykinin failed to evoke a further
      inward current in the presence of Ba(2+). Bradykinin also reduced the amplitude
      of M-current deactivation induced by a hyperpolarizing step from a holding
      potential of -25 mV to -50 mV with a half-maximum effective concentration of 16
      nM. Pretreatment with pertussis toxin had no effect on the bradykinin-induced
      inhibition of the M-current. From these results we suggest that bradykinin may be
      able to depolarize the airway parasympathetic ganglion neurons of rats associated
      with an inhibition of M-type K(+) channels through the B(2) type of bradykinin
      receptors.

PMID- 11516843
TI  - Is the alpha/beta ratio for prostate cancer low?

PMID- 11516844
TI  - Can positron emission tomography improve the quality of care for head-and-neck
      cancer patients?
AB  - PURPOSE: Fluoro-2-deoxy-d-glucose-positron emission tomography (FDG-PET) is a
      functional imaging modality that measures the relative uptake of 18FDG with PET.
      The purpose of this review is to assess the potential contribution of FDG-PET
      scans to the treatment of head-and-neck cancer patients. METHODS AND MATERIALS:
      Data were assessed from the literature with attention to what additional
      information may be gained from the use of FDG-PET in four clinical settings: (1)
      detection of occult metastatic disease in the neck, (2) detection of occult
      primaries in patients with neck metastases, (3) detection of synchronous
      primaries or metastatic disease in the chest, and (4) detection of
      residual/recurrent locoregional disease. RESULTS: Although the data are somewhat
      conflicting, FDG-PET appears to add little additional value to the physical
      examination and conventional imaging studies (supplemented by biopsy when
      appropriate) for the detection of subclinical nodal metastases, unknown
      primaries, or disease in the chest. However, FDG-PET scans are quite useful in
      differentiating residual/recurrent disease from treatment-induced normal tissue
      changes. A positive FDG-PET scan at 1 month after radiotherapy is highly
      indicative of the presence of residual disease, and a negative scan at 4 months
      after treatment is highly predictive of tumor eradication. CONCLUSIONS: Large
      scale studies using newer generation equipment and more defined methods are
      needed to more rigorously assess the potential of FDG-PET in the detection of
      subclinical primary or simultaneous secondary tumors and of nodal or systemic
      spread. Currently, however, FDG-PET can contribute to the detection of
      residual/early recurrent tumors, leading to the timely institution of salvage
      therapy or the prevention of unnecessary biopsies of irradiated tissues, which
      may aggravate injury.

PMID- 11516845
TI  - Lymphocyte radiosensitivity is a significant prognostic factor for morbidity in
      carcinoma of the cervix.
AB  - PURPOSE: To study the relationship between pretreatment peripheral blood
      lymphocyte radiosensitivity and morbidity following radiation therapy. METHODS
      AND MATERIALS: A prospective study was carried out in which patients with
      carcinoma of the cervix underwent radiation therapy. Intrinsic radiosensitivity
      was measured on pretreatment peripheral blood lymphocytes, using a limiting
      dilution clonogenic assay. Late morbidity was assessed using the Franco-Italian
      glossary. Results were correlated in an actuarial analysis. RESULTS: There were
      no correlations between the measured lymphocyte radiosensitivity (SF2) and colony
      forming efficiency, patient age, tumor grade, or disease stage. For 83 patients,
      lymphocyte SF2 was a significant prognostic factor for the probability of
      developing both any (p = 0.002) and Grade 3 (p = 0.026) morbidity. In 174
      patients, stage showed borderline significance as a prognostic factor for
      morbidity (p = 0.056). However, the type of treatment (intracavitary alone,
      intracavitary plus parametrial irradiation, single insertion plus whole-pelvis
      irradiation) was significantly associated with the probability of developing late
      complications (p = 0.013). There was a weak significant inverse correlation
      between lymphocyte SF2 and grade of morbidity (r = -0.34, p = 0.002). CONCLUSION:
      These data highlight the importance of normal cell radiosensitivity as a factor
      determining radiation therapy response. They also show that peripheral blood
      lymphocyte SF2 is a highly significant prognostic factor for the probability of
      developing late radiation morbidity, and that carcinoma of the cervix is a good
      model for testing radiobiologic principles in the clinic.

PMID- 11516846
TI  - Correlation of immunohistochemical molecular staging of bladder biopsies and
      radical cystectomy specimens.
AB  - PURPOSE: To determine the relationship of p53, retinoblastoma (RB), and p16
      expression between precystectomy transurethral resection bladder (TURB) biopsy
      and matched cystectomy specimens; and to determine the value of p53
      immunoreactivity for predicting progression and survival in patients undergoing
      radical cystectomy. METHODS AND MATERIALS: We performed p53 immunohistochemical
      staining on matched archival TURB and cystectomy specimens taken from 40
      patients. Twenty-seven and 26 of these patients were also evaluated for RB and
      p16 expression, respectively. RESULTS: Twenty-eight (70%) of the TURB and 22
      (55%) of the cystectomy specimens stained positive for p53. RB and p16 protein
      expression were altered in 19 (70%) and 19 (73%) of the TURB specimens,
      respectively, and 19 (70%) and 19 (73%) of the cystectomy specimens,
      respectively. There was a strong correlation between p53, RB, and p16 expression
      and TURB and cystectomy specimens (all p < 0.001). In preoperative and
      postoperative multivariate analyses, biopsy p53 and cystectomy p53 were
      independently associated with disease progression (p = 0.049 and p = 0.034,
      respectively) and bladder cancer-related death (p = 0.044 and p = 0.037,
      respectively). CONCLUSION: p53, RB, and p16 expression patterns on TURB specimens
      correlate with cystectomy specimens. p53 immunoreactivity is an independent
      predictor of disease progression and bladder cancer survival. These data support
      the potential of prognostic staging using immunohistochemical analysis on bladder
      biopsy specimens prior to neoadjuvant or definitive therapy.

PMID- 11516847
TI  - Muscle-invasive transitional cell carcinoma of the urinary bladder: a population
      based study of patterns of care and prognostic factors.
AB  - PURPOSE: Population-based cancer registries can permit the study of the
      survivorship of all patients with a particular diagnosis regardless of patterns
      of referral and practice within a specific geographic distribution. The purpose
      of this study is to describe the patterns of care, outcome, and prognostic
      factors for bladder cancer in the northern region of the province of Alberta,
      Canada, between 1984 and 1993. METHODS AND MATERIALS: Between 1984 and 1993, 184
      patients from northern Alberta were identified from the Alberta Cancer Registry
      as having undergone curative treatment for biopsy-proven muscle-invasive
      transitional cell carcinoma of the bladder. Data were obtained, by retrospective
      chart review, regarding the staging, pathology, treatment, and outcome of
      patients treated in the northern Alberta cities of Edmonton, Grande Prairie, and
      Red Deer, regardless of the responsible treating institution. The prognostic
      significance of patient-, tumor-, and treatment-related variables were tested
      using univariate and multivariate analysis using the Cox proportional-hazard
      model. RESULTS: As the primary treatment modality, 74 patients (40%) received
      radical radiotherapy (RT) without surgery; surgery was used alone in 81 patients
      (44%), and was combined with preoperative or postoperative radiotherapy in 29
      patients (16%). Seventy-three (40%) patients also received concurrent,
      neoadjuvant, or adjuvant chemotherapy. The Kaplan-Meier estimate of median
      survival was 2.2 years, and the 5-year overall survival was 30%. Univariate
      analysis demonstrated the prognostic significance of T classification (p <
      0.001), lymph node involvement (p < 0.001), complete response to RT (p = 0.001),
      hydronephrosis (p = 0.017), and vascular/lymphatic involvement (p = 0.035).
      Multivariate analysis revealed the following to have a significant association
      with survival: T classification (p = 0.001), lymph node involvement (p = 0.004),
      complete response to RT (p = 0.054), hydronephrosis (p = 0.019), and use of
      chemotherapy in the treatment regimen (p = 0.025). CONCLUSION: The strongest
      prognostic factors in this study were tumor related, and no significant
      differences in survival were detected between patients treated with primary
      surgery vs. organ-preservation approaches. A survival advantage associated with
      the incorporation of chemotherapy into the management schema was detected on
      multivariate, but not univariate, analysis. Stratification of patients based on
      tumor characteristics is imperative in clinical trials for invasive bladder
      cancer. Novel treatment approaches are required to improve survival further in
      patients with apparently localized disease.

PMID- 11516848
TI  - 10-year biochemical (prostate-specific antigen) control of prostate cancer with
      (125)I brachytherapy.
AB  - PURPOSE: To report 10-year biochemical (prostate-specific antigen [PSA]) outcomes
      for patients treated with 125I brachytherapy as monotherapy for early-stage
      prostate cancer. METHODS AND MATERIALS: One hundred and twenty-five consecutively
      treated patients, with clinical Stage T1-T2b prostate cancer were treated with
      125I brachytherapy as monotherapy, and followed with PSA determinations. Kaplan
      Meier estimates of PSA progression-free survival (PFS), on the basis of a two
      consecutive elevations of PSA, were calculated. Aggregate PSA response by time
      interval was assessed. Comparisons were made to an earlier-treated cohort.
      RESULTS: The overall PSA PFS rate achieved at 10 years was 87% for low-risk
      patients (PSA < 10, Gleason Sum 2-6, T1-T2b). Of 59 patients (47%) followed
      beyond 7 years, 51 (86%) had serum PSAs less than 0.5 ng/mL; 48 (81%) had serum
      PSAs less than 0.2 ng/mL. Failures were local, 3.0%; distant, 3.0%. No patients
      have died of prostate carcinoma. The proportion of patients with a PSA < or =0.2
      ng/mL continued to increase until at least 7-8 years posttherapy. A plot of PSA
      PFS against the proportion of patients achieving serum PSA of less than 0.2 ng/mL
      suggests a convergence of these two endpoints at 10 years. Patients treated in
      the era of this study (1988-1990) experienced a statistically improved PFS
      compared with an earlier era (1986-1987). This difference appears independent of
      patient selection, suggesting that the maturation of the technique resulted in
      improved biochemical control. CONCLUSION: With modern technique, monotherapy with
      125I achieves a high rate (87%) of biochemical and clinical control in patients
      with low-risk disease at 10 years. The decline of PSA following brachytherapy
      with low-dose-rate isotopes can be protracted. Absolute PSA and PFS curves merge,
      and are comparable at 10 years.

PMID- 11516849
TI  - Five-year biochemical outcome following permanent interstitial brachytherapy for
      clinical T1-T3 prostate cancer.
AB  - PURPOSE: To evaluate 5-year biochemical disease-free outcome for men with
      clinical T1b-T3a NxM0 1977 American Joint Committee on Cancer (1997 AJCC)
      adenocarcinoma of the prostate gland who underwent transperineal ultrasound
      guided permanent prostate brachytherapy. METHODS AND MATERIALS: Four hundred
      twenty-five patients underwent transperineal ultrasound-guided prostate
      brachytherapy using either 103Pd or 125I, for clinical T1b-T3a NxM0 (1997 AJCC)
      adenocarcinoma of the prostate gland, from April 1995 to October 1999. No patient
      underwent pathologic lymph-node staging. One hundred ninety patients were
      implanted with either 103Pd or 125I monotherapy; 235 patients received moderate
      dose external beam radiation therapy (EBRT), followed by a prostate brachytherapy
      boost; 163 patients received neoadjuvant hormonal manipulation, in conjunction
      with either 103Pd or 125I monotherapy (77 patients) or in conjunction with
      moderate-dose EBRT and a prostate brachytherapy boost (86 patients). The median
      patient age was 68.0 years (range, 48.2-81.3 years). The median follow-up was 31
      months (range, 11-69 months). Follow-up was calculated from the day of
      implantation. No patient was lost to follow-up. Biochemical disease-free survival
      was defined by the American Society of Therapeutic Radiation and Oncology (ASTRO)
      consensus definition. RESULTS: For the entire cohort, the 5-year actuarial
      biochemical no evidence of disease (bNED) survival rate was 94%. For patients
      with low-, intermediate-, and high-risk disease, the 5-year biochemical disease
      free rates were 97.1%, 97.5%, and 84.4%, respectively. For hormone-naive
      patients, 95.7%, 96.4%, and 79.9% of patients with low-, intermediate-, and high
      risk disease were free of biochemical failure. Clinical and treatment parameters
      predictive of biochemical outcome included: clinical stage, pretreatment prostate
      specific antigen (PSA), Gleason score, risk group, age > 65 years, and
      neoadjuvant hormonal therapy. Isotope choice was not a statistically significant
      predictor of disease-free survival for any risk group. The median postimplant PSA
      was < or = 0.2 for all risk groups, regardless of hormonal status. The mean
      posttreatment PSA, however, was significantly lower for men implanted with 103Pd
      (0.14 ng/mL) than for those implanted with 125I (0.25 ng/mL), p < or = 0.001.
      CONCLUSION: With a median follow-up of 31 months, permanent prostate
      brachytherapy results in a high probability of actuarial 5-year biochemical
      disease-free survival (DFS) for patients with clinical T1b-T3a (1997 AJCC)
      adenocarcinoma of the prostate gland, with an apparent plateau on the PSA
      survival curve.

PMID- 11516850
TI  - Treatment planning aids in prostate cancer: friend or foe?
AB  - BACKGROUND: Rectal barium is commonly used as a treatment planning aid for
      prostate cancer to delineate the anterior rectal wall. Previous research at the
      Ottawa Regional Cancer Centre demonstrated that retrograde urethrography results
      in a systematic shift of the prostate. We postulated that rectal barium could
      also cause prostate motion. PURPOSE: The study was designed to evaluate the
      effects of rectal barium on prostate position. METHODS AND MATERIALS: Thirty
      patients with cT1-T3 prostate cancer were evaluated. Three fiducial markers were
      placed in the prostate. During simulation, baseline posterior-anterior and
      lateral films were taken. Repeat films were taken after rectal barium
      opacification. The prostate position (identified by the fiducials) relative to
      bony landmarks was compared before and after rectal barium. Films were analyzed
      using PIPsPro software. RESULTS: The rectal barium procedure resulted in a
      significant displacement of the prostate in the anterior and superior direction.
      The mean displacement of the prostate measured on the lateral films was 3.8 mm
      (SD: 4.4 mm) in the superior direction and 3.0 mm (SD: 3.1) in the anterior
      direction. CONCLUSIONS: Rectal barium opacification results in a systematic shift
      of the prostate. This error could result in a geographic miss of the target;
      therefore, alternate methods of normal tissue definition should be used.

PMID- 11516851
TI  - Assessment of lung cancer response after nonoperative therapy: tumor diameter,
      bidimensional product, and volume. A serial CT scan-based study.
AB  - PURPOSE: Tumor response after nonoperative lung cancer therapy is traditionally
      evaluated by bidimensional measurement of maximum tumor diameters. The purpose of
      this analysis is to investigate whether tumor largest dimension (based on RECIST
      [Response Evaluation Criteria In Solid Tumors]), bidimensional tumor product, and
      volume correlate with each other in evaluating tumors of patients with locally
      advanced non-small-cell lung cancer (NSCLC). In addition, the pace of locally
      advanced NSCLC volumetric response over time, as well as the prognostic value of
      tumor size, was assessed in this report with software-assisted evaluation of
      sequential tumor measurement. METHODS AND MATERIALS: Patients with locally
      advanced NSCLC treated with thoracic radiotherapy (RT) with or without
      chemotherapy were included, if the following were available: a pretreatment
      computed tomography (CT) simulation and at least two follow-up diagnostic
      thoracic CT scans taken at our institution after 1996 that were available in
      Dicom format for electronic transfer of images from diagnostic radiology to a
      computer terminal with commercial statistics software (AcQsim/CMS Focus). Primary
      lung tumor and grossly involved lymph nodes were contoured manually on pre-RT
      axial images and on all follow-up CT scans. Tumor/lymph node largest dimensions,
      bidimensional products (BP), and volumes were measured using the same software.
      Data were presented as percent change in volume or unidimensional and
      bidimensional measurements, with the CT simulation measurements serving as
      baseline. RESULTS: A total of 22 patients were evaluated. The median thoracic RT
      dose was 62.4 Gy (range: 50.0-69.6), and all patients had a Karnofsky performance
      status > or =80. Chemotherapy (mostly carboplatin/paclitaxel) was given to 17
      patients. Nineteen patients had Stage III NSCLC; 1 patient was in Stage I, 1 was
      in Stage IV, and 1 was recurrent. A total of 107 thoracic CT scans (22
      pretreatment and 85 follow-up), averaging 4.9 scans per patient, were analyzed.
      Tumors reached the smallest volume at a median of 11.0 months from RT completion
      in all patients, 8.5 months in patients who subsequently failed locally (n = 8),
      and 11.9 months in those who did not fail locally. Failure rates were as follows:
      in-field, 36% (8/22); intrathoracic (lung nodules, effusion, pleura), 55%
      (12/22); and distant, 50% (11/22). Eleven patients are still alive, 4 free of
      disease. Overall median survival time (MST) is 27.3 months. The median initial
      tumor volume was 88.0 cc (range: 3.8-218) for all patients; median BP was 33.0
      cm(2) (range: 3.1-112.1), and median tumor largest dimension was 7.6 cm (range:
      2.2-13.5). The MST of patients with initial tumor volume < or =63.0 cc (n = 9)
      was >53.0 months and of those with tumor volume > 63.0 cc was 17.3 months. The
      MST of patients (n = 6) with initial bidimensional tumor product < or =16 cm(2)
      was >53.0 months and of those with tumor product >16 cm(2) was 17.3 months. The
      MST of patients with largest initial dimension < or =4 cm was >53.1 months and of
      those with largest dimension > 4 cm was 25.0 months. At 24 months, 79% of
      patients with a tumor volume < or =124.0 cc (n = 18) had locally controlled
      tumors, vs. 0% of patients with tumor volumes >124.0 cc. At the same time point,
      93% of patients with BP < or =40 cm(2) were locally controlled, vs. 0% of those
      with BP > 40 cm(2); 100% of patients with tumor dimensions < or =7.5 cm were
      locally controlled, vs. 40% of those with dimensions >7.5 cm. The partial
      responses in our series (assessed as the best response obtained during
      observation period) were as follows: 4 patients assessed based on either
      dimension only, product only, or volume only; 15 partial responses based on
      dimension or product; 16 partial responses based on volume alone; 3 cases of no
      tumor response, based on dimension or product; and 2 cases based on tumor volume
      alone. That represents good to excellent agreement among all three methods of
      measurement. CONCLUSIONS: (1) The response of locally advanced NSCLC to
      nonoperative therapy is a slow process, with tumor volumes reaching their nadir
      several months after treatment. (2) Smaller initial tumor size, as measured by
      largest tumor dimension, bidimensional product, or tumor volume, is associated
      with better local control and survival than larger initial measurements. (3) Any
      of the three tumor measurements (largest dimension, bidimensional product, or
      volume) can be used as a reliable tool in assessing lung cancer response to
      nonoperative therapy. This confirms further the validity of RECIST and does not
      suggest that tumor volume is significantly superior for response evaluation.

PMID- 11516852
TI  - Respiratory-driven lung tumor motion is independent of tumor size, tumor
      location, and pulmonary function.
AB  - PURPOSE: To determine whether superior-inferior lung tumor motion is predictable
      by tumor size or location, or pulmonary function test results. METHODS AND
      MATERIALS: Superior-inferior tumor motion was measured on orthogonal radiographs
      taken during simulation of 22 patients with inoperable lung cancer diagnosed by
      orthogonal radiographs. RESULTS: The tumor size averaged 5.5 +/- 3.1 cm (range
      1.5-12 cm). Seven of 11 central tumors demonstrated some motion compared with 5
      of 11 peripheral tumors. Four of 5 upper lobe tumors moved compared with 8 of 17
      tumors that were either middle or lower lobe lesions. The mean fourth rib motion
      was 7.3 +/- 3.2 mm (range 2-15). The mean FeV(1) was 1.8 +/- 1.2 (range 0.55
      5.33. The mean diffusing capacity of the lung for carbon monoxide was 14.0 +/-
      6.5 (range 7.8-21.9). The mean total lung capacity was 6.5 +/- 1.2 (range 3.3
      8.4). None of these parameters correlated with tumor motion. Although lateral
      tumor motion could not be consistently determined, 1 tumor moved 10 mm anterior
      posteriorly. CONCLUSIONS: Lung tumors often move significantly during
      respiration. Tumor motion is not predictable by tumor size or location, or
      pulmonary function test results. Therefore, tumor motion must be measured in all
      patients. Measurement in three dimensions will likely be necessary to maximize
      the irradiated lung volumes or choose beam arrangements parallel to the major
      axis of motion.

PMID- 11516853
TI  - Evaluation of level I and II axillary nodes included in the standard breast
      tangential fields and calculation of the administered dose: results of a
      prospective study.
AB  - PURPOSE: To evaluate if Level I and II axillary nodes are included in the
      standard breast tangential fields, and to calculate the dose administered.
      METHODS AND MATERIALS: In 35 patients treated with conservative surgery and
      axillary dissection, three clips were surgically positioned: one at the beginning
      of Level I, one between Level I and II, and another at the end of Level II. The
      breast was irradiated with two tangential fields. On simulation films, the volume
      between the clips was scored as "entirely included" or "not entirely included" in
      the treatment fields. Computed tomography (CT) scans were performed; CT data were
      imported into a treatment planning system, and three-dimensional plans were
      devised. Axillary Levels I and II were delineated on CT slices on the basis of
      anatomic landmarks. Fields and isodose curves previously obtained were
      superimposed to calculate the dose administered to the first two axillary node
      levels and to 90% of both volumes. RESULTS: On X-rays, the volume between clips
      corresponding to Level I was completely included in the medial field in 66.7% of
      cases and in the lateral field in 63.7% of cases, whereas the volume of Level II
      was entirely included in the medial field in 54.5% of cases and in the lateral
      field in 45.4% of cases. The median dose administered to Level I and II was 38.58
      Gy +/- 11.01 (range 3.46-47.14) and 20.65 Gy +/- 14.07 (range 0.95-38.94),
      respectively. The median dose to 90% of both volumes of Level I and II was 6.75
      Gy +/- 14.01 (range 1.9-39) and 1.75 Gy +/- 9.72 (range 0.8-29), respectively.
      CONCLUSION: The standard tangential fields do not entirely include Levels I and
      II axillary nodes.

PMID- 11516854
TI  - Long-term results of local recurrence after breast conservation treatment for
      invasive breast cancer.
AB  - PURPOSE: The outcome for women with a local failure after breast conservation
      treatment is not well described in the literature. Because local recurrence is a
      potentially salvageable event, this study was performed to evaluate the outcome
      of patients with local recurrence after breast conservation surgery and
      definitive radiation treatment. METHODS AND MATERIALS: The study population
      consisted of 112 patients with ipsilateral breast tumor recurrence. There were
      100 isolated local recurrences and 12 local-plus-regional recurrences. There were
      93 invasive local recurrences and 19 DCIS (ductal carcinoma in situ) local
      recurrences. Local recurrences were detected by physical examination alone in 42
      patients, mammography alone in 47 patients, and both modalities in 23 patients.
      All patients were initially treated with breast conservation treatment with or
      without systemic therapy and subsequently treated at the time of local recurrence
      with salvage mastectomy with or without systemic therapy. The mean and median
      follow-up times after local recurrence were 49 and 44 months, respectively.
      RESULTS: For the entire group of 112 patients, the overall survival at 10 years
      after local recurrence was 69%, the cause-specific survival was 71%, and the
      freedom from distant metastases was 47%. For the 93 patients with an invasive
      local recurrence, the overall survival at 10 years was 64%, cause-specific
      survival was 67%, and freedom from distant metastases was 44%. For the 93
      patients with an invasive local recurrence, interval from diagnosis to local
      recurrence (< or =2 years vs. 2.1-5 years vs. >5 years) predicted for overall
      survival at 5 years (65% vs. 84% vs. 89%; p = 0.03). Method of detection of local
      recurrence (physical examination vs. mammography vs. both methods) also predicted
      for 5-year overall survival (73% vs. 91% vs. 93%, respectively; p = 0.04). On
      multivariable analysis, interval from diagnosis to local recurrence was an
      independent predictor of overall survival (p = 0.03). Method of detection of
      local recurrence (physical examination vs. mammography vs. both methods) was
      borderline in predicting for 5-year cause-specific survival (73% vs. 91% vs. 93%,
      respectively; p = 0.06). Similarly, interval from diagnosis to local recurrence
      (< or =2 years vs. 2.1-5 years vs. >5 years) was a borderline predictor of 5-year
      cause-specific survival (65% vs. 84% vs. 89%; p = 0.08). No factors that
      predicted for freedom from distant metastases were identified. There were three
      second locoregional failures on the chest wall. Two of the 19 patients with a
      DCIS local recurrence have died of metastatic breast cancer. Death was probably
      not related to their local recurrence, but rather a result of persistent risk
      from an invasive primary cancer. CONCLUSIONS: This analysis provides long-term
      data after salvage treatment for patients who experience local recurrence after
      breast conservation treatment. The variables of method of detection and interval
      from diagnosis to local recurrence are identified as having prognostic
      significance for overall and cause-specific survival. In view of the potential
      for long-term survival, aggressive attempt at salvage treatment is warranted for
      the patient with local recurrence after breast conservation treatment. Second
      local recurrence after salvage mastectomy is an uncommon event. Although DCIS
      local recurrences may not in themselves cause an increase in the risk of
      mortality, the risk from the primary invasive cancer persists.

PMID- 11516855
TI  - Phase II study assessing the effectiveness of Biafine cream as a prophylactic
      agent for radiation-induced acute skin toxicity to the breast in women undergoing
      radiotherapy with concomitant CMF chemotherapy.
AB  - PURPOSE: To assess the efficacy of Biafine cream in preventing Grade 2 acute
      radiation dermatitis, according to the National Cancer Institute of Canada skin
      radiation toxicity criteria in patients undergoing concomitant adjuvant
      chemotherapy and radiotherapy to the breast. METHODS AND MATERIALS: Sixty
      patients participated in this study. Patients were treated with a lumpectomy
      followed by concomitant chemotherapy and radiotherapy to the breast. Biafine
      cream was applied daily, starting on the first day and ending 2 weeks post
      radiotherapy. Patients underwent weekly skin assessments throughout radiotherapy
      and at 2 and 4 weeks after treatment. Outcome measures were assessed using a Skin
      Assessment Questionnaire that was scored according to the National Cancer
      Institute of Canada skin radiation toxicity criteria and a self-administered
      questionnaire that evaluated skin symptoms. RESULTS: The maximum skin toxicity
      observed during the course of treatment was as follows: less than Grade 2
      toxicity, 15% (9 patients); Grade 2, 83% (50 patients); Grade 3, 2% (1 patient);
      Grade 4, 0% (0 patients). The majority of the radiation dermatitis was observed
      after 3 weeks of radiotherapy. CONCLUSION: The majority of patients who underwent
      concomitant chemo- and radiotherapy for breast cancer developed Grade 2 radiation
      dermatitis with the use of Biafine cream. However, no treatment delays or
      interruptions were observed because of skin toxicity.

PMID- 11516856
TI  - Definitive intraoperative very high-dose radiotherapy for localized osteosarcoma
      in the extremities.
AB  - PURPOSE: To evaluate the outcome and adverse effects in patients with
      osteosarcoma treated with very high-dose definitive intraoperative radiotherapy
      (IORT), with the intention of saving the affected limb. METHODS AND MATERIALS:
      Thirty-nine patients with osteosarcoma in their extremities were treated with
      definitive IORT. The irradiation field included the tumor plus an adequate wide
      margin and excluded the major vessels and nerves. Forty-five to 80 Gy of
      electrons or X-rays were delivered. The median follow-up of the surviving
      patients was 124 months. RESULTS: The cause-specific and relapse-free 5-year
      survival rate was 50% and 43%, respectively. Distant metastasis developed in 23
      patients; 19 died and 4 were alive for >10 years. Nine local recurrences were
      found 4-29 months after IORT in the affected limb. No radiation-induced skin
      reaction or nerve palsy was observed in the patients treated with X-rays.
      Experiments using phantoms also confirmed that the scatter dose was below the
      toxic level in the IORT setting with X-rays. CONCLUSIONS: Very high-dose
      definitive IORT combined with preventive nailing and chemotherapy appeared to be
      a promising quality-of-life-oriented alternative to treating patients with
      osteosarcomas in the extremities, although the problem of recurrences from the
      surrounding unirradiated soft tissue remains to be solved.

PMID- 11516857
TI  - Correlation of intraoperatively irradiated volume and fibrosis in patients with
      soft-tissue sarcoma of the extremities.
AB  - PURPOSE: To investigate the influence of intraoperatively irradiated volume on
      soft-tissue fibrosis. METHODS AND MATERIALS: Fifty-three patients with soft
      tissue sarcoma of the extremities were treated with intraoperative radiotherapy
      (IORT) (median dose 15 Gy) and postoperative fractionated therapy (median dose 46
      Gy). The median follow-up was 41.5 months (range 18-94). Late toxicity was
      classified according to the LENT-SOMA criteria. A Cox regression model was
      calculated to identify the parameters that could influence soft-tissue fibrosis
      Grade 3 or 4. Five parameters were observed: extent of surgical procedure, IORT
      in case of recurrence, extent of IORT volume, extent of IORT dose, and extent of
      postoperative volume. In addition, a logistic regression model was calculated to
      demonstrate the relationship between the IORT volume and fibrosis development.
      RESULTS: The overall survival rate after 5 years was 84%. The actuarial tumor
      control rate was 90% after 5 years. Eleven patients developed soft-tissue
      fibrosis. Five patients developed Grade 3 fibrosis and 1 patient developed Grade
      4 fibrosis. Only the IORT volume had a significant influence on Grade 3 or 4
      fibrosis development. An IORT volume of 210 cm(3) conveyed a 5% risk (confidence
      interval 1-20%) of the development of severe fibrosis. The risk of severe Grade 3
      or 4 fibrosis increased to 50% (confidence interval 15-80%) if a volume of 420
      cm(3) was irradiated. CONCLUSION: The effect of volume in patients treated with
      IORT was remarkable. The ratio of side effects was relatively low. The risk of
      soft-tissue Grade 3 or 4 fibrosis increased with the extent of the IORT volume.
      Compared with the literature, IORT provides excellent local control in these
      patients.

PMID- 11516858
TI  - A population-based study of glioblastoma multiforme.
AB  - PURPOSE: To describe (1) the use of surgery and radiotherapy (RT) in the
      treatment of patients with glioblastoma (GBM) in Ontario, (2) survival, and (3)
      proportion of survival time spent in the hospital after diagnosis. METHODS AND
      MATERIALS: We performed a population-based cohort study of all Ontario Cancer
      Registry (OCR) cases of GBM diagnosed between 1982 and 1994. We linked OCR
      records, hospital files containing surgical procedure codes from the Canadian
      Institute for Health Information, and province-wide RT records. We studied the
      odds of treatment using multivariate logistic regression. We expressed the time
      spent in the hospital as the mean number of days per case, and as a proportion of
      the interval between diagnosis and death, or 24 months following diagnosis,
      whichever came first. We used the life-table method and Cox proportional hazards
      regression to describe survival. RESULTS: The proportion of patients with GBM
      undergoing any surgery directed at the tumor varied with age (p < 0.0001) and
      region of residence (p < 0.0001). The proportion undergoing RT varied with age (p
      < 0.0001), region of residence (p < 0.0001), and year of diagnosis (p = 0.01). RT
      dose > or = 53.5 Gy varied with age (p < 0.0001), region of residence (p <
      0.0001), and year of diagnosis (p = 0.0002). Median survival was 11 months among
      patients receiving RT and 3 months among those not receiving RT. The percentage
      of survival time spent in the hospital was similar among those who received from
      49.5 to < 53.5 Gy, compared to > or = 53.5 Gy. Overall survival and the adjusted
      relative risk of death varied with age and region of residence. CONCLUSION: We
      observed practice variation in the treatment of patients with GBM according to
      age, region of residence, and year of diagnosis. Survival did not increase during
      the study period. The variation in RT dose between those receiving from 49.5 to <
      53.5 Gy compared to > or =53.5 Gy was not paralleled by variation in survival
      between regions where one or the other of the dose ranges predominated, nor was
      variation in dose ranges among the regions paralleled by variation in the
      proportion of survival time spent in the hospital.

PMID- 11516859
TI  - Stereotactic radiotherapy for pediatric intracranial germ cell tumors.
AB  - PURPOSE: Intracranial germ cell tumors are rare, radiosensitive tumors seen most
      commonly in the second and third decades of life. Radiotherapy alone has been the
      primary treatment modality for germinomas, and is used with chemotherapy for
      nongerminomatous tumors. Stereotactic radiotherapy techniques minimize the volume
      of surrounding normal tissue irradiated and, hence, the late radiation morbidity.
      This study reports our experience with stereotactic radiotherapy in this group of
      tumors. METHODS AND MATERIALS: Between December 1992 and December 1998, 18
      patients with intracranial germ cell tumors were treated with stereotactic
      radiotherapy. A total of 23 histologically proven tumors were treated. Thirteen
      patients had a histologic diagnosis of germinoma, and 5 patients had germinoma
      with nongerminomatous elements. Of those patients with a histologic diagnosis of
      germinoma, 5 had multiple midline tumors. The median age of the patients was 12.9
      years (range, 5.6-17.5 years). RESULTS: A boost using stereotactic radiotherapy
      was delivered to 19 tumors following whole-brain radiation in 8 cases and
      craniospinal radiation in 11 cases. Three tumors were treated with stereotactic
      radiotherapy to the tumor volume alone following chemotherapy, and 1 tumor
      received a boost using stereotactic radiosurgery following craniospinal
      radiation. A median dose of 2520 cGy (range, 1500-3600) cGy was given to the
      whole brain, and a median dose of 2160 (range, 2100-2600) cGy was given to the
      spinal field. The median boost dose to the tumor was 2600 (range, 2160-3600) cGy,
      given by stereotactic radiotherapy delivered to the 95% isodose line. At a median
      follow-up time of 40 (range, 12-73) months, no local or marginal recurrences were
      reported in patients with germinoma. Two patients with nongerminomatous tumors
      have relapsed. One had elevation of tumor markers only at 37 months following
      treatment, and the other had persistent disease following chemotherapy and
      radiation therapy. Eight patients documented pituitary-hypothalamic dysfunction;
      in 7 (87.5%) of these patients, the dysfunction was present before commencing
      radiotherapy. Four patients (22%) developed newly diagnosed diabetes insipidus
      following surgery. Three patients (17%) received antidepressant medication at
      follow-up. CONCLUSION: Our series shows that stereotactic radiotherapy is
      achievable and well tolerated in this group of patients. Longer follow-up is
      required to fully assess the impact on long-term toxicity. Psychologic assessment
      of mood and affect should be performed as part of routine follow-up in this group
      of adolescent children.

PMID- 11516860
TI  - Phase II radiation therapy oncology group trial of weekly paclitaxel and
      conventional external beam radiation therapy for supratentorial glioblastoma
      multiforme.
AB  - PURPOSE: Fractionated external beam radiotherapy (EBRT) +/- carmustine (BCNU) is
      the standard of care for patients with glioblastoma multiforme (GBM), but
      survival results remain poor. Preclinical studies indicate synergy between RT and
      paclitaxel (TAX) in astrocytoma cell lines. Phase I studies in GBM have
      demonstrated a maximum tolerated dose for TAX of 225 mg/m(2)/3 h/week x 6, during
      EBRT, with no exacerbation of typical RT-induced toxicities. The Radiation
      Therapy Oncology Group (RTOG) therefore mounted a Phase II study to determine the
      feasibility and efficacy of conventional EBRT and concurrent weekly TAX at its
      MTD. PATIENTS AND METHODS: Sixty-two patients with histologic diagnosis of GBM
      were enrolled from 8/16/96 through 3/21/97 in a multi-institutional Phase II
      trial of EBRT and TAX 225 mg/m(2)/3 h (1-3 h before EBRT), administered the first
      treatment day of each RT week. Total EBRT dose was 60 Gy (200 cGy/fraction), 5
      days per week. A smaller treatment field, to include gross disease plus a margin
      only, was used after 46 Gy. RESULTS: Sixty-one patients (98%) were evaluable.
      Median age was 55 years (range, 28-78). Seventy-four percent were > or = 50
      years. Recursive partitioning analysis (RPA) Classes III, IV, V, VI included 10
      (17%), 21 (34%), 25 (41%), and 5 (8%) patients, respectively. Gross total
      resection was performed in only 16%. There was no Grade 3 or 4 neutropenia or
      thrombocytopenia. Hypersensitivity reactions precluding further use of TAX
      occurred in 4 patients. There were 2 instances of late neurotoxicity (4% Grade 3
      or 4). Ninety-one percent of patients received treatment per protocol. Seventy
      seven percent completed prescribed treatment (6 weeks). Of 35 patients with
      measurable disease, CR/PR was observed in 23%, MR in 17%, and SD in 43%.
      Seventeen percent demonstrated progression at first follow-up. Median potential
      follow-up time is 20 months. Median survival is 9.7 months, with median survivals
      for RPA classes III, IV, V, and VI of 16.3, 10.2, 9.5, 2.5 months, respectively.
      Ten patients remain alive. CONCLUSION: Concurrent full-dose EBRT and weekly high
      dose TAX is feasible in the majority of GBM patients. Acute toxicity is
      acceptable; myelosuppression and peripheral sensory neuropathy are surprisingly
      modest, despite considerably higher overall dose intensity, compared to that
      achievable in other disease sites. Median survival by RPA class without prolonged
      adjuvant therapy is comparable to RTOG controls treated with standard EBRT and
      BCNU (1 year of BCNU).

PMID- 11516861
TI  - Optimal timing of neutron irradiation for boron neutron capture therapy after
      intravenous infusion of sodium borocaptate in patients with glioblastoma.
AB  - PURPOSE: A cooperative study in Europe and Japan was conducted to determine the
      pharmacokinetics and boron uptake of sodium borocaptate (BSH: Na(2)B(12)H(11)SH),
      which has been introduced clinically as a boron carrier for boron neutron capture
      therapy in patients with glioblastoma. METHODS AND MATERIALS: Data from 56
      patients with glioblastoma who received BSH intravenous infusion were
      retrospectively reviewed. The pharmacokinetics were evaluated in 50 patients, and
      boron uptake was investigated in 47 patients. Patients received BSH doses between
      12 and 100 mg/kg of body weight. For the evaluation, the infused boron dose was
      scaled linearly to 100 mg/kg BSH. RESULTS: In BSH pharmacokinetics, the average
      value for total body clearance, distribution volume of steady state, and mean
      residence time was 3.6 +/- 1.5 L/h, 223.3 +/- 160.7 L, and 68.0 +/- 52.5 h,
      respectively. The average values of the boron concentration in tumor adjusted to
      100 mg/kg BSH, the boron concentration in blood adjusted to 100 mg/kg BSH, and
      the tumor/blood boron concentration ratio were 37.1 +/- 35.8 ppm, 35.2 +/- 41.8
      ppm, and 1.53 +/- 1.43, respectively. A good correlation was found between the
      logarithmic value of T(adj) and the interval from BSH infusion to tumor tissue
      sampling. About 12-19 h after infusion, the actual values for T(adj) and
      tumor/blood boron concentration ratio were 46.2 +/- 36.0 ppm and 1.70 +/- 1.06,
      respectively. The dose ratio between tumor and healthy tissue peaked in the same
      interval. CONCLUSION: For boron neutron capture therapy using BSH administered by
      intravenous infusion, this work confirms that neutron irradiation is optimal
      around 12-19 h after the infusion is started.

PMID- 11516862
TI  - Dose-escalation with proton/photon irradiation for Daumas-Duport lower-grade
      glioma: results of an institutional phase I/II trial.
AB  - PURPOSE: The role of dose escalation with proton/photon radiotherapy in lower
      grade gliomas was assessed in a prospective Phase I/II trial. We report the
      results in terms of local control, toxicity, and survival. MATERIALS AND METHODS:
      Twenty patients with Grade 2/4 (n = 7) and Grade 3/4 (n = 13) gliomas according
      to the Daumas-Duport classification were treated on a prospective institutional
      protocol at Massachusetts General Hospital/Harvard Cyclotron Laboratory between
      1993 and 1996. Doses prescribed to the target volumes were 68.2 cobalt Gray
      equivalent (CGE, 1 proton Gray = 1.1 CGE) to gross tumor in Grade 2 lesions and
      79.7 CGE in Grade 3 lesions. Fractionation was conventional, with 1.8 to 1.92 CGE
      once per day. Eligibility criteria included age between 18 and 70 years, biopsy
      proven Daumas-Duport Grade 2/4 or 3/4 malignant glioma, Karnofsky performance
      score of 70 or greater, and supratentorial tumor. Median age of the patient
      population at diagnosis was 35.9 years (range 19-49). Ten tumors were mixed
      gliomas, one an oligodendroglioma. RESULTS: Five patients underwent biopsy, 12 a
      subtotal resection, and 3 a gross total resection. Median interval from surgery
      to first radiation treatment was 2.9 months. Actuarial 5-year survival rate for
      Grade 2 lesions was 71% as calculated from diagnosis (median survival not yet
      reached); actuarial 5-year survival for Grade 3 lesions was 23% (median 29
      months). Median follow-up is 61 months and 55 months for 4 patients alive with
      Grade 2 and 3 patients alive with Grade 3 lesions, respectively. Three patients
      with Grade 2 lesions died from tumor recurrence, whereas 2 of the 4 survivors
      have evidence of radiation necrosis. Eight of 10 patients who have died with
      Grade 3 lesions died from tumor recurrence, 1 from pulmonary embolus, and 1 most
      likely from radiation necrosis. One of 3 survivors in this group has evidence of
      radiation necrosis. CONCLUSION: Tumor recurrence was neither prevented nor
      noticeably delayed in our patients relative to published series on photon
      irradiation. Dose escalation using this fractionation scheme and total dose
      delivered failed to improve outcome for patients with Grade 2 and 3 gliomas.

PMID- 11516863
TI  - Maximizing local tumor control and survival after proton beam radiotherapy of
      uveal melanoma.
AB  - PURPOSE: This study reports local tumor control and survival after proton beam
      radiotherapy (PBRT) of uveal melanoma. It identifies the risk factors for local
      tumor-control failure and for ocular tumor-related death. It presents the
      improvements implemented to increase the rate of local tumor control, and
      compares the survival rate of patients with locally controlled tumors to those of
      patients who had to receive a second treatment. PATIENTS AND METHODS: We have
      treated 2,435 uveal melanomas with PBRT between March 1984 and December 1998.
      Data were analyzed as of September 1999. Patients' age ranged from 9 to 89 years;
      there were 1,188 men and 1,247 women. The largest tumor diameter ranged from 4 to
      26 mm, and tumor thickness from 0.9 to 15.6 mm. Median follow-up time was 40
      months. RESULTS: Local tumor control probability at 5 years was improved from
      90.6 +/- 1.7% for patients treated before 1988, to 96.3 +/- 0.6% for patients
      treated between 1989 and 1993, and became 98.9 +/- 0.6% for patients treated
      after 1993. Among 2,435 treated patients, 73 (3%) had to receive a second
      treatment because of tumor regrowth. Cause-specific survival at 10 years was
      calculated to 72.6 +/- 1.9% for patients with controlled tumors compared to 47.5
      +/- 6.5% for those with recurrent tumors. CONCLUSION: Reduced safety margins,
      large ciliary body tumors, eyelids within the treatment field, inadequate
      positioning of tantalum clips, and male gender were identified to be the main
      factors impairing local tumor control. The improvement of local tumor control
      rate after 1993 is attributed to changes implemented in the treatment procedure.
      Our data strongly support that the rate of death by metastases is influenced by
      local tumor control failure: improvement of the local tumor control rate results
      in a better survival rate.

PMID- 11516864
TI  - A high and sustained response rate in refractory or relapsing low-grade lymphoma
      masses after low-dose radiation: analysis of predictive parameters of response to
      treatment.
AB  - PURPOSE: To determine the efficacy of small doses of radiation in patients with
      recurrent or refractory low-grade lymphoma masses. METHODS AND MATERIALS:
      Patients with refractory or relapsing low-grade lymphoma masses. The two largest
      diameters of the tumor mass were measured, whenever possible, before and after
      treatment. A dose of 4 Gy of radiotherapy was delivered to tumor sites in 2
      fractions. Patients were evaluated for response 1-4 months later and at regular
      follow-up visits. RESULTS: Forty-eight patients with low-grade lymphomas
      according to the working formulation received low-dose radiotherapy between March
      1987 and November 1998. Most patients had advanced disease at the time of
      radiation treatment, and 80% had received at least two chemotherapy regimens
      before treatment. The median interval between the initial diagnosis and
      radiotherapy was 2.7 years (range 0-22 years). Low-dose radiation was delivered
      to 135 tumor sites. Nodal and extranodal tumor sites represented 80% and 20% of
      masses, respectively. An objective response was obtained in 81% of the sites,
      with 57% attaining a complete remission. The 2-year actuarial freedom from local
      progression (FFLP) rate was 56% (95% CI, 46-66%). Tumor masses </=5 cm in
      diameter had a significantly higher 2-year FFLP rate than larger masses (51% vs.
      27%). It is noteworthy that the 2-year FFLP rate for patients treated with less
      than 2 chemotherapy regimens before radiotherapy was significantly higher than
      the 2-year FFLP rate for more heavily treated patients (96% vs. 48%). The 2-year
      FFLP rates for extranodal tumor sites and nodal sites were not significantly
      different. The tumor size (< or =5 cm vs. > 5 cm), the number of chemotherapy
      regimens (0-1 vs. more), and age at time of radiation treatment (< or =65 years
      or > 65 years) were significant predictive parameters of response to treatment.
      CONCLUSIONS: In this retrospective study, low-dose radiation proved efficient,
      with long-lasting effects in the majority of patients with recurrent or
      refractory low-grade lymphomas. This simple and nontoxic treatment should be
      investigated prospectively in patients with advanced disease and a low tumor
      burden not immediately warranting chemotherapy.

PMID- 11516865
TI  - Analysis of toxicity of Merkel cell carcinoma of the skin treated with
      synchronous carboplatin/etoposide and radiation: a Trans-Tasman Radiation
      Oncology Group study.
AB  - PURPOSE: The acute and late toxicities of synchronous carboplatin, etoposide, and
      radiation therapy were prospectively assessed in a group of patients with high
      risk Merkel cell carcinoma of the skin. PATIENTS AND METHODS: Forty patients from
      six different centers throughout Australia were entered into a Phase II study
      under the auspices of the Trans-Tasman Radiation Oncology Group. The trial was
      activated in 1996 and continues to accrue. Patients are eligible if they have
      disease localized to the primary site and nodes and are required to have at least
      one of the following high-risk features: recurrence after initial therapy,
      involved nodes, primary size greater than 1 cm, gross residual disease after
      surgery, or occult primary with nodes. Radiation was delivered to the primary
      site and nodes to a dose of 50 Gy in 25 fractions over 5 weeks, and synchronous
      carboplatin (area under curve [AUC] 4.5) and etoposide (80 mg/M(2) i.v.) were
      given on days 1-3 during weeks 1, 4, 7, and 10. The median age of the group was
      67 years (43-78). RESULTS: The median duration of follow-up was 22 months (2-45).
      There were no treatment-related deaths. Grade 3 or 4 skin toxicity occurred in
      63% of patients (95% CI 48, 78). The most serious acute effect was on neutrophils
      with Grade 3 or 4 (neutrophils < 1 x 10(9)/L), occurring in 60% (95% CI 45, 75)
      of cases. Complications from neutropenia (fever and sepsis) occurred in 16
      patients (40% of cases). The median time for neutropenic complications was 27
      days (9-35), and 10/16 (62%) cases of neutropenic fever occurred after the second
      cycle of chemotherapy. The probability of Grade 3 or 4 late effects on platelets
      (<50 x 10(9)/L) and hemoglobin (<8 g/dl) was 10% (95% CI 1, 20) and 6% (95% CI 2,
      15), respectively. Of the 40 patients, 35 were able to complete 4 cycles of
      chemotherapy. There were no factors predictive for neutropenic toxicity at a p
      value < 0.05. CONCLUSIONS: The protocol has acceptable toxicity, and the
      treatment has been deliverable in a multi-institutional trial setting.
      Neutropenia is likely to occur with synchronous carboplatin/etoposide and
      radiation in this population of patients. The risk of a febrile neutropenia was
      greatest at the time of the second cycle of chemotherapy, when there was moist
      desquamation of skin or mucosal membranes that provided a portal for infection.
      This should be considered in the design of subsequent protocols with
      chemoradiotherapy.

PMID- 11516866
TI  - Fractionated stereotactic radiosurgery for 50 patients with recurrent or residual
      nasopharyngeal carcinoma.
AB  - PURPOSE: This study was conducted to evaluate the clinical value of fractionated
      stereotactic radiosurgery (FSRS) as a boost treatment in 44 patients with
      residual or recurrent nasopharyngeal carcinoma after conventional radiotherapy
      (70-80 Gy) or a second course of radiotherapy (50 Gy) or as salvage treatment in
      6 patients with recurrent nasopharyngeal carcinoma after a first or second course
      of radiotherapy at the primary site. METHODS AND MATERIALS: From September 20,
      1995 to December 30, 1998, 50 patients were treated with FSRS with 6 MV of
      photons. The total FSRS dose was 14-35 Gy (median dose 24) prescribed at 1-4
      centers on the 60-90% isodose curves normalized to the isocenter by multiple
      fractions of 6-8, 12, or 15 Gy, with interfraction intervals of 4-6 days.
      RESULTS: Thirty-eight patients (76%) had a complete tumor response, 9 (18%) had a
      partial response, and 3 (6%) were not assessable. The overall rate of survival
      was 83.6% at 1 year, 65.0% at 2 years, and 59.6% at 3 years. The overall disease
      free survival rate among patients with residual tumor was 89.94% at 1 year,
      73.97% at 2 years, and 73.97% at 3 years. Patients who were treated for recurrent
      lesions or who received FSRS as salvage therapy had a 46.53% rate of disease-free
      survival at both 1 and 2 years after therapy. CONCLUSION: FSRS is strongly
      indicated for recurrent or residual nasopharyngeal carcinoma at the primary site.

PMID- 11516867
TI  - Phase III trial of high- vs. low-dose-rate interstitial radiotherapy for early
      mobile tongue cancer.
AB  - PURPOSE: Early mobile tongue cancer can be controlled with interstitial
      radiotherapy (ISRT). We carried out a Phase III trial to compare the treatment
      results of low-dose-rate (LDR) ISRT and high-dose-rate (HDR) ISRT for early
      mobile tongue cancer. METHODS AND MATERIALS: From April 1992 through October
      1996, 59 patients with cancer of the early mobile tongue were registered in this
      Phase III study. Eight patients were excluded from the evaluation because of
      violations of the requirements for this study. Of 51 eligible patients, 26
      patients were treated with LDR-ISRT (70 Gy/4-9 days) and 25 patients with HDR
      ISRT (60 Gy/10 fractions/1 week). For the hyperfractionated HDR-ISRT, the time
      interval between 2 fractions was more than 6 h. RESULTS: Five-year local control
      rates of the LDR and HDR groups were 84% and 87% respectively. Nodal metastasis
      occurred in 6 patients in each group. Five-year nodal control rates of the LDR
      and HDR groups were 77% and 76%, respectively. CONCLUSION: Hyperfractionated HDR
      ISRT for early mobile tongue cancer has the same local control compared with
      continuous LDR-ISRT. Hyperfractionated HDR-ISRT is an alternative treatment for
      continuous LDR-ISRT.

PMID- 11516868
TI  - T4 rectal cancer treated with preoperative chemoradiation to the posterior pelvis
      followed by multivisceral resection: patterns of failure and limitations of
      treatment.
AB  - PURPOSE: To analyze the overall pattern of treatment failure and sites of pelvic
      disease recurrence relative to the radiation fields used in treating patients
      with clinically staged T4 rectal cancer with preoperative chemoradiation followed
      by multivisceral resection. METHODS AND MATERIALS: Between 1990 and 1998, 45
      patients with T4 rectal cancer were treated with preoperative chemoradiation.
      Clinical staging was according to the system of the American Joint Cancer
      Committee and was based on endoscopic ultrasonography, chemotherapy (CT), and
      physical examination. A diagnosis of T4 disease required evidence of invasion of
      a contiguous structure on CT (n = 31) or endorectal ultrasonography (n = 6),
      vaginal mucosal involvement on pelvic examination (n = 6), or a combination of
      these findings (n = 2). Chemoradiation was delivered with 18 MV photons using a 3
      field belly-board technique. The median total dose was 45 Gy in all patients
      (range 45-63). Nine patients received a boost with external beam radiotherapy
      (EBRT) (n = 5, 1.8-18 Gy), intraoperative RT (n = 3, 10-20 Gy), or interstitial
      brachytherapy (n = 1, 20 Gy). All patients received concurrent chemotherapy
      consisting of protracted venous infusion 5-fluorouracil (300 mg/m(2), 5 d/wk).
      Resection was not performed in 13 (29%) of the 45 patients because of metastases
      detected before resection or patient refusal. Multivisceral resection and pelvic
      exenteration was required in 21 (66%) and 11 (34%) of 32 patients, respectively.
      We compared the location of pelvic disease recurrence with the RT simulation
      films. The Kaplan-Meier method was used to calculate the 4-year actuarial pelvic
      and distant recurrent rates and the overall survival rate. RESULTS: The median
      length of follow-up was 31.0 months for all patients and 40.0 months for patients
      alive at last follow-up. When only the resected cases were considered, the local
      recurrence rate was 20%. Distant metastases occurred in 44% of cases; the overall
      survival rate was 69%. When all patients were considered, the local recurrence
      rate was similar (24%), but the rate of distant recurrence (51%) was higher and
      the overall survival rate lower (50%). Pelvic disease was controlled in all 8
      patients whose disease responded well to chemoradiation (either a histologically
      complete response or microscopic residual disease). Three of 4 patients with
      close or positive margins had pelvic recurrences despite intraoperative RT and
      brachytherapy. Nine of the 10 pelvic recurrences occurred in the radiation field.
      Elective external iliac nodal irradiation was not used, and nodal metastases were
      not seen in that region. In 1 case, marginal recurrence occurred in a common
      iliac node at the superior edge of the treatment field. CONCLUSIONS: Despite
      aggressive multimodality therapy including multivisceral resection, a high rate
      of pelvic and distant disease recurrence occurred in patients with clinically
      staged T4 disease. Regional disease recurred almost exclusively in the radiation
      field. The intraoperative RT and interstitial brachytherapy doses used did not
      prevent pelvic disease recurrence in patients with close or positive margins.
      Novel strategies such as higher preoperative doses of RT with or without altered
      fractionation or more effective radiosensitizers are needed to improve
      locoregional control in patients with T4 disease. Future strategies must also
      include more effective systemic therapy.

PMID- 11516869
TI  - The effect of ionizing radiation on intraocular lenses.
AB  - BACKGROUND: The native crystalline lens is the principal shield against
      ultraviolet radiation (UV), damage to the human retina. Every year in the United
      States, more than one million patients undergo removal of the natural lens in the
      course of cataract surgery (phakectomy), at which time an intraocular lens (IOL)
      is placed in the lens capsule. The IOL thenceforth serves as the principal
      barrier to ultraviolet radiation over the life of the implant, potentially for
      decades. The synthetic organic molecules of which IOLs are composed offer little
      UV protection unless ultraviolet-absorbing chromophores are incorporated into the
      lens material during manufacture. However, chromophores are alkenes potentially
      subject to radiolytic degradation. It is unknown whether ionizing radiation at
      clinical doses (e.g., to the brain or in the head-and-neck region) affects the UV
      absorbing capacity of chromophore-bearing IOLs and consequently exposes the
      retina to potentially chronic UV damage. In addition, the polymers of which IOLs
      are composed are themselves subject to radiation damage, which theoretically
      might result in optical distortion in the visible light range. OBJECTIVE: To
      determine whether megavoltage photon ionizing radiation alters the absorption
      spectra of ultraviolet-shielding polymethylmethacrylate (PMMA) and
      organopolysiloxane (silicone) intraocular lenses (IOLs) in the UV (280 nm < or =
      lambda < 400 nm), visible (400 nm < or = lambda < or = 700 nm), and low-end near
      infrared (700 nm < lambda < or = 830 nm) ranges. DESIGN: Prospective,
      nonrandomized trial of dose-paired IOL cohorts. METHODS: Fourteen IOLs, seven of
      PMMA (Chiron 6842B) and seven of silicone (IOLAB L141U), were paired and examined
      for absorption spectra in 1-nm intervals over the range lambda = 280-830 nm on a
      Cary 400 deuterium and quartz halogen source-lamp UV/visible spectrophotometer
      before and after undergoing megavoltage ionizing irradiation to doses of 2, 5,
      10, 20, 40, 60, and 100 Gray, respectively. Because of artifactual aberrations
      inherent in analyzing convex lenses on a conventional flat-plate
      spectrophotometer, post-irradiation absorption spectra were subsequently
      reanalyzed on a Cary 300 spectrophotometer outfitted with a Labsphere Diffused
      Reflectance Accessory (DRA-CA-30-I) incorporating a Spectralon-coated integrating
      sphere. MAIN OUTCOME MEASURES: Primary: Changes in UV absorbance after
      irradiation. Secondary: Changes in visible and low-end near-infrared absorbance
      after irradiation. RESULTS: Photon ionizing radiation in the 2-Gy to 100-Gy range
      produced no detectable alterations in the UV (280 nm < or = lambda < 400 nm),
      visible (400 nm < or = lambda < or = 700 nm), or low-end near-infrared (700 nm <
      lambda < or = 830 nm) absorption spectra of any of the lenses irradiated.
      However, silicone IOLs as a group revealed peak post-irradiation UV absorption at
      a shorter wavelength than did PMMA IOLs, with marginally greater UV transmission
      at the uppermost extreme of the UV spectrum (lambda = 384.5-400 nm). CONCLUSIONS:
      At clinically relevant doses used in radiation therapy, megavoltage photon
      ionizing radiation produces no significant alterations in the absorption spectra
      of PMMA and silicone IOLs over the range lambda = 280- 830 nm. These findings
      indicate that, even at supraclinical doses, the UV-absorbing capacity of
      chromophore-bearing PMMA and silicone IOLs remains unimpaired. It is not clear
      whether the lower UV peak of silicone lenses represents a radiation effect or a
      peculiarity of the chromophore used in the lenses tested.

PMID- 11516870
TI  - Financial compensation for radiotherapy-related adverse events in a judicial
      system where proof of medical negligence is not required.
AB  - PURPOSE: To examine the frequency of adverse events related to radiation therapy
      that lead to financial compensation in a judicial system that is not based on
      litigation in court but on statutory insurance where proof of medical negligence
      is not required for obtaining compensation. METHODS AND MATERIALS: In Finland, an
      injured patient does not sue through the courts, but submits an insurance claim
      to the Patient Insurance Association. Proof of medical negligence is not required
      for obtaining compensation. We reviewed all filed claims associated with
      radiotherapy presented to the Patient Insurance Association from May 1987 to
      January 1999. During this time period, 1,732,000 patient visits to radiation
      therapy units were made, and the estimated number of radiotherapy treatments was
      86,600. The data collected included descriptions of the adverse events,
      examination of the radiation therapy procedures followed, assessment of the
      causal relation of the event to radiotherapy by the therapists involved and by
      independent reviewers, and the sums used for compensation. RESULTS: Only 102
      patients (about 0.1%) had filed a claim for financial compensation, and in 18
      (0.02%) cases the claim led to compensation. The mean national annual expenditure
      used for compensation was $35,200, and the sums paid in single cases ranged from
      $310 to $287,430 (median, $1,970). The expenditure used for compensating adverse
      radiation events was about $4 per treated patient, which is about 0.3% of all
      radiation therapy costs. CONCLUSIONS: The frequency of radiation therapy injuries
      that are financially compensated can remain low in an insurance-based judicial
      system where no litigation or attorneys are involved.

PMID- 11516871
TI  - A simple analytic derivation suggests that prostate cancer alpha/beta ratio is
      low.

PMID- 11516872
TI  - Clinical implications of incomplete repair parameters for rat spinal cord: the
      feasibility of large doses per fraction in PDR and HDR brachytherapy.
AB  - PURPOSE: To evaluate the clinical implications of the repair parameters
      determined experimentally in rat spinal cord and to test the feasibility of large
      doses per fraction or pulses in daytime high-dose-rate (HDR) or pulsed-dose-rate
      (PDR) brachytherapy treatment schedules as an alternative to continuous low-dose
      rate (CLDR) brachytherapy. METHODS AND MATERIALS: BED calculations with the
      incomplete repair LQ-model were performed for a primary CLDR-brachytherapy
      treatment of 70 Gy in 140 h or a typical boost protocol of 25 Gy in 50 h after 46
      Gy conventional external beam irradiation (ERT) at 2 Gy per fraction each day.
      Assuming biphasic repair kinetics and a variable dose rate for the iridium-192-
      (192Ir) stepping source, the LQ-model parameters for rat spinal cord as derived
      in three different experimental studies were used: (a) two repair processes with
      an alpha/beta ratio = 2.47 Gy and repair half-times of 0.2 h (12 min) and 2.2 h
      (Pop et. al.); (b) two repair processes with an alpha/beta ratio = 2.0 Gy and
      repair half-times of 0.7 h (42 min) and 3.8 h (Ang et al.); and (c) two repair
      processes with an alpha/beta ratio = 2.0 Gy and repair half-times of 0.25 h (15
      min) and 6.4 h (Landuyt et al.). For tumor tissue, an alpha/beta ratio of 10 Gy
      and a monoexponential repair half time of 0.5 h was assumed. The calculated BED
      values were compared with the biologic effect of a clinical reference dose of
      conventional ERT with 2 Gy/day and complete repair between the fractions.
      Subsequently, assuming a two-catheter implant similar to that used in our
      experimental study and with the repair parameters derived in our rat model, BED
      calculations were performed for alternative PDR- and HDR-brachytherapy treatment
      schedules, in which the irradiation was delivered only during daytime. RESULTS:
      If the repair parameters of the study of Pop et al., Ang et al., or Landuyt et
      al. are used, for a CLDR-treatment of 70 Gy in 140 h, the calculated BED values
      were 117, 193, or 216 Gy(sc) (Gy(sc) was used to express the BED value for the
      spinal cord), respectively. These BED values correspond with total doses of
      conventional ERT of 65, 96, or 104 Gy. The latter two are unrealistic high values
      and illustrate the danger of a straightforward comparison of BED values if repair
      parameters are used in situations quite different from those in which they were
      derived. For a brachytherapy boost protocol, the impact of the different repair
      parameters is less, due to the fact that the percentage increase in total BED
      value by the brachytherapy boost is less than 50%. If a primary treatment with
      CLDR brachytherapy delivering 70 Gy in 140 h has to be replaced, high doses per
      fraction or pulses (> 1 Gy) during daytime can only be used if the overall
      treatment time is prolonged with 3-4 days. The dose rate during the fraction or
      pulse should not exceed 6 Gy/h. For a typical brachytherapy boost protocol after
      46 Gy ERT, it seems to be safe to replace CLDR delivering a total dose of 25 Gy
      in 50 h by a total dose of 24 Gy in 4 days with HDR or PDR brachytherapy during
      daytime only. Total dose per day should be limited to 6 Gy, and the largest time
      interval as possible between each fraction or pulse should be used. CONCLUSION:
      Extrapolations based on longer repair half-times in a CLDR reference scheme may
      lead to the calculation of unrealistically high BED values and dangerously high
      doses for alternative HDR and PDR treatment schedules. Based on theoretical
      calculations with the IR model and using the repair parameters derived in our rat
      spinal cord model, it is estimated that with certain restrictions, large doses
      per fraction or pulses can be used during daytime schedules of HDR or PDR
      brachytherapy as an alternative to CLDR brachytherapy, especially for those
      treatment conditions in which brachytherapy is used after ERT for only less than
      50% of the total dose.

PMID- 11516873
TI  - Image-based dose planning of intracavitary brachytherapy: registration of serial
      imaging studies using deformable anatomic templates.
AB  - PURPOSE: To demonstrate that high-dimensional voxel-to-voxel transformations,
      derived from continuum mechanics models of the underlying pelvic tissues, can be
      used to register computed tomography (CT) serial examinations into a single
      anatomic frame of reference for cumulative dose calculations. METHODS AND
      MATERIALS: Three patients with locally advanced cervix cancer were treated with
      CT-compatible intracavitary (ICT) applicators. Each patient underwent five
      volumetric CT examinations: before initiating treatment, and immediately before
      and after the first and second ICT insertions, respectively. Each serial
      examination was rigidly registered to the patient's first ICT examination by
      aligning the bony anatomy. Detailed nonrigid alignment for organs (or targets) of
      interest was subsequently achieved by deforming the CT exams as a viscous-fluid,
      described by the Navier-Stokes equation, until the coincidence with the
      corresponding targets on CT image was maximized. In cases where ICT insertion
      induced very large and topologically complex rearrangements of pelvic organs,
      e.g., extreme uterine canal reorientation following tandem insertion, a viscous
      fluid-landmark transformation was used to produce an initial registration.
      RESULTS: For all three patients, reasonable registrations for organs (or targets)
      of interest were achieved. Fluid-landmark initialization was required in 4 of the
      11 registrations. Relative to the best rigid bony landmark alignment, the viscous
      fluid registration resulted in average soft-tissue displacements from 2.8 to 28.1
      mm, and improved organ coincidence from the range of 5.2% to 72.2% to the range
      of 90.6% to 100%. Compared to the viscous-fluid transformation, global
      registration of bony anatomy mismatched 5% or more of the contoured organ volumes
      by 15-25 mm. CONCLUSION: Pelvic soft-tissue structures undergo large deformations
      and displacements during the external-beam and multiple-ICT course of radiation
      therapy for locally advanced cervix cancer. These changes cannot be modeled by
      the conventional rigid landmark transformation method. In the current study, we
      found that the deformable anatomic template registration method, based on
      continuum-mechanics models of deformation, successfully described these large
      anatomic shape changes before and after ICT. These promising modeling results
      indicate that realistic registration of the cumulative dose distribution to the
      organs (or targets) of interest for radiation therapy of cervical cancers is
      achievable.

PMID- 11516874
TI  - Forward or inversely planned segmental multileaf collimator IMRT and sequential
      tomotherapy to treat multiple dominant intraprostatic lesions of prostate cancer
      to 90 Gy.
AB  - PURPOSE: To investigate the technical feasibility of using forward or inversely
      planned segmental multileaf collimator (SMLC) intensity-modulated radiotherapy
      and sequential tomotherapy (ST) to escalate to a dose of 90 Gy to multiple
      dominant intraprostatic lesions within the prostate gland while delivering a dose
      of 75.6 Gy to the remaining prostate. METHODS AND MATERIALS: A selected case with
      one dominant intraprostatic lesion located at the left base and a second dominant
      intraprostatic lesion at the right apex of the prostate was planned using three
      different intensity modulation techniques. Two plans were generated with inverse
      treatment planning, using either SMLC or ST with a special multivane collimator.
      The third plan also employed SMLC but was generated using forward planning. All
      three plans were compared based on dose-volume histograms, isodose distributions,
      and doses to sensitive normal structures. RESULTS: All three plans meet and
      exceed the desired dose constraints, limiting doses to the rectum and bladder to
      an estimated RTOG Grade 2 complication rate of <10%. The ST plan achieved the
      best dose conformality, whereas the inverse SMLC plan gave the lowest dose to the
      rectal wall, and the forward SMLC plan obtained the best dose homogeneity inside
      the targets. CONCLUSIONS: Using any of the three intensity-modulated techniques,
      it is technically feasible to concurrently treat multiple selected high-risk
      regions within the prostate to 90 Gy and the remaining prostate to 75.6 Gy, while
      keeping the doses to the rectum and the bladder significantly lower than those
      associated with a Grade 2 complication rate of 10%.

PMID- 11516875
TI  - Multimodality image registration quality assurance for conformal three
      dimensional treatment planning.
AB  - PURPOSE: We present a quality assurance methodology to determine the accuracy of
      multimodality image registration and fusion for the purpose of conformal three
      dimensional and intensity-modulated radiation therapy treatment planning.
      Registration and fusion accuracy between any combination of computed tomography
      (CT), magnetic resonance (MR), and positron emission computed tomography (PET)
      imaging studies can be evaluated. METHODS AND MATERIALS: A commercial
      anthropomorphic head phantom filled with water and containing CT, MR, and PET
      visible targets was modified to evaluate the accuracy of multimodality image
      registration and fusion software. For MR and PET imaging, the water inside the
      phantom was doped with CuNO(3) and 18F-fluorodeoxyglucose (18F-FDG),
      respectively. Targets consisting of plastic spheres and pins were distributed
      throughout the cranium section of the phantom. Each target sphere had a conical
      shaped bore with its apex at the center of the sphere. The pins had a conical
      extension or indentation at the free end. The contours of the spheres, sphere
      centers, and pin tips were used as anatomic landmark models for image
      registration, which was performed using affine coordinate-transformation tools
      provided in a commercial multimodality image registration/fusion software
      package. Four sets of phantom image studies were obtained: primary CT, secondary
      CT with different phantom immobilization, MR, and PET study. A novel CT, MR, and
      PET external fiducial marking system was also tested. RESULTS: The registration
      of CT/CT, CT/MR, and CT/PET images allowed correlation of anatomic landmarks to
      within 2 mm, verifying the accuracy of the registration software and spatial
      fidelity of the four multimodality image sets. CONCLUSIONS: This straightforward
      phantom-based quality assurance of the image registration and fusion process can
      be used in a routine clinical setting or for providing a working image set for
      development of the image registration and fusion process and new software.

PMID- 11516876
TI  - Intensity-modulated radiation therapy (IMRT) reduces small bowel, rectum, and
      bladder doses in patients with cervical cancer receiving pelvic and para-aortic
      irradiation.
AB  - PURPOSE: The emergent use of combined modality approach (chemotherapy and
      radiation therapy) for the treatment of patients with cervical cancer is
      associated with significant gastrointestinal and genitourinary toxicity.
      Intensity-modulated radiation therapy (IMRT) has the potential to deliver
      adequate dose to the target structures while sparing the normal organs and could
      also allow for dose escalation to grossly enlarged metastatic lymph node in
      pelvic or para-aortic area without increasing gastrointestinal/genitourinary
      complications. We conducted a dosimetric analysis to determine if IMRT can meet
      these objectives in the treatment of cervical cancer. METHODS AND MATERIALS:
      Computed tomography scan studies of 10 patients with cervical cancer were
      retrieved and used as anatomic references for planning. Upon the completion of
      target and critical structure delineation, the imaging and contour data were
      transferred to both an IMRT planning system (Corvus, Nomos) and a three
      dimensional planning system (Focus, CMS) on which IMRT as well as conventional
      planning with two- and four-field techniques were derived. Treatment planning was
      done on these two systems with uniform prescription, 45 Gy in 25 fractions to the
      uterus, the cervix, and the pelvic and para-aortic lymph nodes. Normalization was
      done to all IMRT plans to obtain a full coverage of the cervix with the 95%
      isodose curve. Dose-volume histograms were obtained for all the plans. A
      Student's t test was performed to compute the statistical significance. RESULTS:
      The volume of small bowel receiving the prescribed dose (45 Gy) with IMRT
      technique was as follows: four fields, 11.01 +/- 5.67%; seven fields, 15.05 +/-
      6.76%; and nine fields, 13.56 +/- 5.30%. These were all significantly better than
      with two-field (35.58 +/- 13.84%) and four-field (34.24 +/- 17.82%) conventional
      techniques (p < 0.05). The fraction of rectal volume receiving a dose greater
      than the prescribed dose was as follows: four fields, 8.55 +/- 4.64%; seven
      fields, 6.37 +/- 5.19%; nine fields, 3.34 +/- 3.0%; in contrast to 84.01 +/-
      18.37% with two-field and 46.37 +/- 24.97% with four-field conventional technique
      (p < 0.001). The fractional volume of bladder receiving the prescribed dose and
      higher was as follows: four fields, 30.29 +/- 4.64%; seven fields, 31.66 +/-
      8.26%; and nine fields, 26.91 +/- 5.57%. It was significantly worse with the two
      field (92.89 +/- 35.26%) and with the four-field (60.48 +/- 31.80%) techniques (p
      < 0.05). CONCLUSION: In this dosimetric study, we demonstrated that with similar
      target coverage, normal tissue sparing is superior with IMRT in the treatment of
      cervical cancer.

PMID- 11516877
TI  - Determination of ventilatory liver movement via radiographic evaluation of
      diaphragm position.
AB  - PURPOSE: To determine the accuracy of estimation of liver movement inferred by
      observing diaphragm excursion on radiographic images. METHODS AND MATERIALS:
      Eight patients with focal liver cancer had platinum embolization microcoils
      implanted in their livers during catheterization of the hepatic artery for
      delivery of regional chemotherapy. These patients underwent fluoroscopy, during
      which normal breathing movement was recorded on videotape. Movies of breathing
      movement were digitized, and the relative projected positions of the diaphragm
      and coils were recorded. For 6 patients, daily radiographs were also acquired
      during treatment. Retrospective measurements of coil position were taken after
      the diaphragm was aligned with the superior portion of the liver on digitally
      reconstructed radiographs. RESULTS: Coil movement of 4.9 to 30.4 mm was observed
      during normal breathing. Diaphragm position tracked inferior-superior coil
      displacement accurately (population sigma 1.04 mm) throughout the breathing
      cycle. The range of coil movement was predicted by the range of diaphragm
      movement with an accuracy of 2.09 mm (sigma). The maximum error observed
      measuring coil movement using diaphragm position was 3.8 mm for a coil 9.8 cm
      inferior to the diaphragm. However, the distance of the coil from the top of the
      diaphragm did not correlate significantly with the error in predicting liver
      excursion. Analysis of daily radiographs showed that the error in predicting coil
      position using the diaphragm as an alignment landmark was 1.8 mm (sigma) in the
      inferior-superior direction and 2.2 mm in the left-right direction, similar in
      magnitude to the inherent uncertainty in alignment. CONCLUSIONS: This study
      demonstrated that the range of ventilatory movement of different locations within
      the liver is predicted by diaphragm position to an accuracy that matches or
      exceeds existing systems for ventilatory tracking. This suggests that the
      diaphragm is an acceptable anatomic landmark for radiographic estimation of liver
      movement in anterior-posterior projections for most patients.

PMID- 11516879
TI  - Excerpts from TIAFT 2000. Selected papers from the 38th Meeting of the
      International Association of Forensic Toxicologists (TIAFT), Helsinki, Finland,
      13-17 August 2000.

PMID- 11516878
TI  - Advancements in cancer therapy with alpha-emitters: a review.
AB  - PURPOSE: This synopsis attempts to shed light on the progresses made in the field
      of cancer therapy using alpha-particles. HURDLES AND PROGRESSES: The rationale of
      selection of radionuclides focusing on comparison of alpha- and beta-emitters,
      the hurdles and their solutions, and recent developments are addressed. The
      efforts made in the field of alpha-radioimmunotherapy of hematologic malignancies
      are emphasized. A good deal of progress has been achieved in the past decade, and
      preclinical studies with a variety of radioimmunoconjugates with astatine and
      bismuth radioisotopes (At-211, Bi-212, and Bi-213) have generated encouraging
      results, providing an impetus for future clinical trials. CONCLUSION: The onset
      of early clinical trials with alpha-emitters will hopefully enable the cancer
      researchers to come up with extremely effective and highly specific "smart bombs"
      to target cancer cells.

PMID- 11516880
TI  - Workplace drug testing in Europe.
AB  - Not much information is available on workplace drug testing (WDT) in Europe.
      There is no specific legislation and there are no generally accepted guidelines.
      Many companies establish a drug policy with little or no provisions for drug
      testing. Often, testing is performed on-site by occupational physicians, with
      little or no quality control, no systematic confirmation of positives, no chain
      of custody and no adulteration testing. In some parts of Europe, e.g. in the
      United Kingdom and some Scandinavian countries, WDT is increasing in importance,
      but it is not as widespread as in USA. The most frequently performed tests are
      amphetamines, cannabinoids, cocaine, opiates and alcohol. The percentage of
      positives is variable, but seems to decrease with the years following the
      introduction of WDT. Cannabis is the drug that is most frequently found.Recently,
      the European Workplace Drug Testing Society (EWDTS) was founded, with the aims to
      ensure that WDT in Europe is performed to a defined quality standard and in a
      legally secured way and to provide an independent forum for all aspects of WDT.A
      working group in the United Kingdom has recently finalised the United Kingdom
      laboratory guidelines for legally defensible WDT and discussions are under way
      with the EWDTS to establish common guidelines. Many efforts will be needed to
      establish WDT as an accepted part of a company policy on drugs: establishing and
      maintaining the confidence in the results of the laboratory, establishing the
      legal status of WDT, preserving the privacy and rights of the employees, proving
      the cost-effectiveness of WDT in a European context, finding a balance between
      strict guidelines and enough flexibility to tailor testing to the changing needs.
      It is hoped that the exchange of experience between different countries will
      contribute to reaching these goals.

PMID- 11516881
TI  - Legal, workplace, and treatment drug testing with alternate biological matrices
      on a global scale.
AB  - Global trends in drug trafficking and drug usage patterns indicate a continuing
      pattern of escalation throughout the world. Over the last two decades, urinalysis
      has evolved into a highly accurate means for determining whether individuals have
      been exposed to illicit drugs of abuse. Advances have also been made in the use
      of alternate biological matrices such as hair, oral fluids and sweat for drug
      testing. Often, these new matrices demonstrate some distinct advantages over
      urinalysis, e.g. less invasive procedures, different time course of drug
      detection. They may even indicate impairment. National and local laws of each
      country provide the underpinnings of drug-testing programs, but most countries
      have not addressed use of these alternate matrices. Currently, only a few
      countries have statutes that specifically mention use of alternate biological
      matrices, e.g. United States (Florida state law), Germany, Ireland, Poland and
      the Czech Republic. Conversely, few countries have prohibited collection of
      alternate biological specimens or drug test devices that utilize such specimens.
      In addition, guidelines for implementing drug testing programs have been slow to
      emerge and most deal primarily with workplace drug testing programs, e.g. United
      States. Currently, scientific technology utilized in drug testing is advancing
      rapidly, but there is a clear need for parallel development of guidelines
      governing the use of alternate matrices for drug testing. This article provides
      an overview of global drug trafficking patterns and drug use, and results from a
      survey of legal statutes in 20 countries covering use of alternate matrices for
      drug testing. In addition, elements needed for the development of guidelines for
      alternate matrices testing for drugs of abuse are discussed, and specific
      examples of use of alternate matrices in treatment monitoring are provided.

PMID- 11516882
TI  - Experience with urine drug testing by the Correctional Service of Canada.
AB  - The Correctional Service of Canada implemented a urine drug-screening program
      over 10 years ago. The objective of this report is to describe the program and
      drug test results in this program for 1999. Offenders in Canadian federal
      correctional institutions and those living in the community on conditional
      release were subject to urine drug testing. Urine specimens were collected at
      correctional facilities and shipped by courier to MAXXAM Analytics Inc.
      laboratory. All urine specimens were analyzed for amphetamines, cannabinoids,
      cocaine metabolite (benzoylecgonine), opiates, phencyclidine, benzodiazepines,
      methyl phenidate, meperidine, pentazocine and fluoxetine by immunoassay screening
      (homogeneous EIA and ELISA assays) followed by GC-MS confirmation. Ethyl alcohol
      was analyzed when specifically requested. Alternative screening and confirmation
      methods with lower cut-off values were used, whenever urine specimens were dilute
      (creatinine <20mg/dl and specific gravity <or=1.003). The number of urine
      specimens analyzed was 44,722 in 1999 and 6.2% of these specimens were dilute
      based on creatinine and specific gravity analysis. The positive rate for one or
      more drugs was 25.5% in 1999. The highest drug positive rates were for
      cannabinoids (10.7%), morphine (3.2%), cocaine metabolite (3.2%), codeine (2.6%),
      oxazepam (2.1%), temazepam (1.1%) and ethyl alcohol (1.0%). In correctional
      institutions (8606 non-dilute specimens analyzed in 1999), 16.4% were positive
      for cannabinoids, 4.9% positive for codeine and/or morphine and 2.7% positive for
      oxazepam and/or temazepam. In the 537 dilute specimens collected in institutions,
      21% were positive for cannabinoids, 1.3% positive for codeine and/or morphine and
      1.3% positive for oxazepam and/or temazepam. In the community setting, 33,928 non
      dilute specimens were collected in 1999 (9.0% were positive for cannabinoids and
      3.5% positive for cocaine metabolite). In the 1651 dilute specimens collected
      from offenders in the community in 1999, 12.6% were positive for cannabinoids and
      9.5% positive for cocaine metabolite. We conclude that forensic urine drug
      testing provides an objective measure of drug use by offenders in Canadian
      federal institutions and those offenders living in the community on conditional
      release.

PMID- 11516883
TI  - Medical prescription of heroin to chronic heroin addicts in Switzerland - a
      review.
AB  - In 1994, a new project dealing with the treatment of heroin dependency was
      introduced in Switzerland. A group of heavy opiate addicts, who had failed in
      previous medical therapies, received heroin by prescription, supported by health
      and social services. The admission criteria to this treatment are summarized as
      the main results of this project: physical and mental health of the addicts
      improved on average during treatment, an improvement also took place in their
      social reintegration, a significant decrease in consumption of illegal drugs took
      place and illegal activities declined massively. The proportion of patients who
      continued the treatment in a time period of 12 months was held at 76%. Comparison
      of the treatment costs with the economic benefits shows that there is a total
      benefit per patient and per day of 26 US dollars. Further drug related political
      decisions in Switzerland as well as the assessments of the International
      Narcotics Control Board (INCB) of the United Nations to this project will be
      reported and discussed.

PMID- 11516884
TI  - External quality assessment of laboratory performance in analysis of
      toxicological cases.
AB  - A mean of 44 members of the United Kingdom national external quality assessment
      scheme (UKNEQAS) for toxicology reported analytical findings on 10 toxicological
      cases circulated between December 1995 and February 2000. Material distributed
      usually consisted of a 5ml blood and a 20ml urine sample simulated by
      quantitative addition of drugs and their metabolites to material donated by
      volunteers and patients. The samples were accompanied by a brief outline of the
      circumstances surrounding the case. Laboratories were requested to report their
      analytical findings, list methods of analysis, and provide interpretation of
      their findings. The mean overall success rate for identification of drugs or
      their pharmacological group was 76%, failure being largely by laboratories
      providing an immunoassay-based screening service for a fixed range of drug
      groups. The latter laboratories indicated that cases would be referred to
      regional toxicology centres for further investigation or confirmation. The
      coefficient of variation of measurements was <7% for routine analytes, such as
      ethanol and paracetamol, but 26-44% for tricyclics and opiates. There were 3%
      false positive reports. The quantity and content of interpretative comment
      provided by the laboratories was very variable. A number provide nothing in
      addition to the analytical result.

PMID- 11516885
TI  - Practical aspects of roadside tests for administrative traffic offences in
      Germany.
AB  - In the context of the European project ROSITA, the Institut of Legal Medicine
      Homburg/Saar has co-operated with the Saarland traffic police in order to assess
      different roadside drug tests for their functionality and reliability in traffic
      controls, and for their analytical force of evidence. In 254 cases within the
      time period from June 1999 to December 1999, police officers performed a
      (voluntary) roadside drug testing in saliva/sweat, or urine, to confirm or refute
      their initial suspicion that a driver had used drugs. Whereas in 45 cases the
      tests gave negative results (which were confirmed by lab urinalysis), in 209
      cases the police officers ordered blood samples after a positive outcome of the
      tests. In 203 of the 209 positive cases, the results could be confirmed by GC/MS
      analysis. Regarding the prevalence of used drugs, a single consumption was found
      in 156 cases (113 cannabis, 38 amphetamines/methamphetamines, three opiates, two
      cocaine), and a consumption of two drugs was found in 44 cases (34
      cannabis+amphetamines/methamphetamines, five cannabis+opiates, three cannabis +
      cocaine, two cocaine+amphetamines/methamphetamines). In three cases, multi
      consumption was found. In six cases, the performed tests gave an incorrect
      prediction to the police officer at the roadside.The roadside tests gave 97.6%
      correct assistance to the police officers in the right direction (79.9% correct
      positive predictions and 17.7% correct negative predictions). As a consequence,
      the performed tests can be seen as a positive and needful tool for the police to
      get an immediate response to their initial suspicion and to take the right steps
      concerning a following legal action.

PMID- 11516886
TI  - A comparison between on-site immunoassay drug-testing devices and laboratory
      results.
AB  - The aim with this study was to evaluate the accuracy of several on-site testing
      devices on the market. A part of this study is included in the European Union's
      (EU's) roadside testing assessment project (ROSITA). An other request for this
      kind of study came from the Finnish prison department in the Ministry of Justice.
      The evaluation was performed on both urine assays and oral fluid assays. The on
      site test results were compared with laboratory results (gas chromatography-mass
      spectrometry (GC/MS)). The samples were tested on amphetamines (AMP),
      cannabinoids (THC), opiates (OPI) and cocaine metabolites (COC). Some of the
      tests also included a metamphetamine (MET) and a benzodiazepine (BZO) test. Both
      positive and negative samples were tested. A total of 800 persons and eight on
      site devices for urine and two for oral fluid testing were included in this
      study. Good results were obtained for the urine on-site devices, with accuracies
      of 93-99% for amphetamines, 97-99% for cannabinoids, 94-98% for opiates and 90
      98% for benzodiazepines. However, differences in the ease of performance and
      interpretation of test result were observed. It was possible to detect
      amphetamines and opiates in oral fluid by the used on-site devices, but the
      benzodiazepines and cannabinoids did not fulfil the needs of sensitivity.

PMID- 11516887
TI  - Piperazine-like compounds: a new group of designer drugs-of-abuse on the European
      market.
AB  - 1-Aryl-piperazine compounds are, depending on their substituents, selective for
      certain serotonin receptors and together with their easy availability and their
      so-called legal status, this group of psychoactive compounds are potential
      designer drugs-of-abuse. Internet in that respect is an important source of
      information and distribution facilities. Because this development may have
      consequences for the interpretation of future clinical and forensic toxicological
      case studies, some analytical aspects of 1-benzyl-piperazine (BZP), 1-[4
      methoxyphenyl]-piperazine (pMeOPP) and 1-[3-trifluoromethylphenyl]-piperazine
      (TFMPP) were studied. BZP was not detected by the AxSYM FPIA technology designed
      to determine amphetamine-like compounds, but had showed some cross reactivity
      with EMIT d.a.u.. The cross reactivities at 300 and 12,000ng/ml (RS)-amphetamine
      equivalents were 0.4 and 1.3%, respectively. Although BZP was not identified
      directly by the REMEDi HS Drug Profiling System, it can be detected by this
      HPLC/UV scanning system. Using GC/NPD without derivatisation, BZP, pMeOPP and
      TFMPP can be analysed for and applying GC/MS without or with acetylation or
      trifluoroacetylation, these compounds can be identified unambiguously. The
      usefulness of GC/NPD and GC/MS in this respect was demonstrated by the
      quantitative and qualitative analysis of the content of a capsule with the
      synthetic stimulant A2, which proved to contain 86.4mg of BZP.

PMID- 11516888
TI  - Detection and assay of cis- and trans-isomers of 4-methylaminorex in urine,
      plasma and tissue samples.
AB  - The 4-methylaminorex (4-MAX) is an amphetamine-related psychostimulant drug that
      has appeared on the clandestine market with a street name of "U4Euh". This
      compound exists as four stereoisomers, trans-4R,5R, trans-4S,5S, cis-4R,5S and
      cis-4S,5R, of which the cis forms have been classified as Schedule I substances
      in the US. The increasing variety of designer drugs has highlighted the
      importance of detection, identification, and quantitative measurement of these
      drugs, including 4-MAX, in biological samples. In the present study, the isomers
      of 4-MAX were detected in urine of rats treated with the drugs by some but not
      all of the on-site immunoassays tested, mainly as amphetamine or methamphetamine.
      To facilitate identification of 4-MAX by laboratories specialized in drug
      analysis, the electron-ionization mass spectrum and TLC data for underivatized 4
      MAX using a routine laboratory drug-screening procedure is provided. In addition,
      a GC/MS method is described for the quantitative determination of cis- and trans
      4-MAX as tert-butyldimethylsilyl-derivatives in plasma, urine and tissue.

PMID- 11516889
TI  - Deaths involving buprenorphine: a compendium of French cases.
AB  - Buprenorphine at high dosage became available in France in 1996, as a
      substitution treatment for heroin addicts. Since this date, numerous deaths were
      attributed to this drug. This paper reports two original series of 39 and 78
      fatalities involving buprenorphine observed at the Institute of Legal Medicine of
      Strasbourg and at 13 other French forensic centers, respectively. The files were
      recorded from January 1996-May 2000. The first 20 fatalities that were previously
      published were excluded from this epidemiological study. From these 117 subjects,
      96 were male (82%). Buprenorphine and its primary metabolite norbuprenophine were
      assayed in post-mortem blood by HPLC/MS (n=11 labs) or by GC/MS (n=3 labs). Blood
      levels for buprenorphine ranged from 0.5 to 51.0ng/ml (mean 10.2ng/ml) and 0.1 to
      76ng/ml (mean 12.6ng/ml) in Strasbourg and the other centers, respectively. Blood
      levels for norbuprenorphine ranged from 0.2 to 47.1ng/ml (mean 8.2ng/ml) and <0.1
      to 65ng/ml (mean 10.6ng/ml) in Strasbourg and the other centers, respectively.
      The mean values appear to be within the therapeutic range. Buprenorphine was
      identified in 24 of the 26 hair samples assayed in Strasbourg, at concentrations
      ranging from 10 to 1080pg/mg. Intravenous injection of crushed tablets, a
      concomitant intake of psychotropics (especially benzodiazepines and neuroleptics)
      and the high dosage of the buprenorphine formulation available in France appear
      as the major risk factors for such fatalities. In addition, two suicide-related
      deaths were also observed, with blood buprenorphine concentrations at 144 and
      3276ng/ml.

PMID- 11516890
TI  - Postmortem tissue concentrations of venlafaxine.
AB  - Venlafaxine is a phenethylamine antidepressant which inhibits both serotonin and
      norepinephrine reuptake and is structurally unrelated to the serotonin reuptake
      inhibitors (SSRIs). Its major metabolite, O-desmethylvenlafaxine (ODV), also
      inhibits serotonin reuptake. Although metabolized by the cytochrome P-450 (CYP)
      system, venlafaxine inhibits CYP 2D6 and 3A4 to a far lesser extent than do the
      SSRIs. Mechanisms of drug action are reviewed and evaluated in the investigation
      of 12 fatalities occurring over a 6-month-period where venlafaxine was
      detected.Venlafaxine and ODV were identified by liquid chromatography-mass
      spectrometry (LC-MS) using atmospheric pressure ionization (API) electrospray in
      positive mode following an n-butyl chloride extraction. Postmortem tissue
      concentrations studied in each of 12 postmortem cases for venlafaxine and ODV,
      were 0.1-36 and <0.05-3.5mg/l (peripheral blood), <0.05-22 and <0.05-9.9mg/kg
      (liver), <0.05-10 and <0.05-1.5mg/l (vitreous), <0.05-53 and <0.05-6.8mg/l
      (bile), <0.05-55 and <0.05-21mg/l (urine), respectively, and 0.1-200mg of
      venlafaxine in the gastric contents. Venlafaxine was typically present with other
      drugs, including other antidepressants, alcohol, and benzodiazepines. The
      potential for interaction with each drug is discussed. Over the 6-month-period of
      this study, there were no deaths ascribed solely to venlafaxine intoxication.

PMID- 11516891
TI  - Analysis of fatty acid ethyl esters in hair as possible markers of chronically
      elevated alcohol consumption by headspace solid-phase microextraction (HS-SPME)
      and gas chromatography-mass spectrometry (GC-MS).
AB  - Fatty acid ethyl esters (FAEE) are products of the nonoxidative ethanol
      metabolism, which are known to be detectable in blood only about 24h after the
      last alcohol intake. After deposition in hair they should be suitable long-term
      markers of chronically elevated alcohol consumption. Therefore, a method for the
      analysis of ethyl myristate, ethyl palmitate, ethyl oleate and ethyl stearate
      from hair was developed based on the extraction of the hair sample by a
      dimethylsulphoxide (DMSO)/n-hexane mixture, separation and evaporation of the n
      hexane phase and application of headspace solid-phase microextraction (HS-SPME)
      in combination with gas chromatography-mass spectrometry (GC-MS) to the extract.
      For use as internal standards, the corresponding D(5)-ethyl esters were prepared.
      The HS-SPME/GC-MS measurements were automatically performed using a multi-purpose
      sampler. The detection limits of the FAEE were between 0.01 and 0.04ng/mg and the
      reproducibility was between 3.5 and 16%. By application of the method to hair
      samples of 21 fatalities with known heavy alcohol abuse 0.045-2.4ng/mg ethyl
      myristate, 0.35-13.5ng/mg ethyl palmitate, 0.25-7.7ng/mg ethyl oleate and 0.05
      3.85ng/mg ethyl stearate were measured. For social drinkers (30-60g ethanol per
      week), the concentrations were about one order of magnitude smaller. For 10
      teetotalers negative results or traces of ethyl palmitate were found. It was
      shown by supplementary investigations in single cases that FAEE are also present
      in sebum, that there is no strong difference in their concentrations between
      pubic, chest and scalp hair, and that they are detectable in hair segments after
      a 2 months period of abstinence. From the results follows that the measurement of
      FAEE concentrations in hair is a useful way for a retrospective detection of
      alcohol abuse.

PMID- 11516892
TI  - Screening for the presence of drugs in serum and urine using different separation
      modes of capillary electrophoresis.
AB  - Capillary electrophoresis (CE) is a modern separation technique that has some
      distinct advantages for toxicological analysis, such as a high efficiency, fast
      analysis, flexibility, and complementary separation mechanisms to chromatographic
      methods. CE can be applied in various modes, which each have a different
      separation mechanism or selectivity. The most common mode is capillary zone
      electrophoresis (CZE), in which charged analytes migrate in a buffer under the
      influence of an electric field. In micellar electrokinetic chromatography (MEKC),
      micelles are added to the buffer which interact with the analytes. MEKC can also
      be used for the separation of neutral compounds. In non-aqueous CE (NACE), the
      aqueous buffer is replaced by a background of electrolytes in organic solvents. A
      sample that needs to be screened can easily be analyzed subsequently by these CE
      modes using the same instrumentation. The aim of the study was to develop
      procedures for the analysis of basic and acidic drugs in serum and urine using
      CZE, MEKC, and NACE. A test mixture that consisted of six basic and six acidic
      compounds was used to study the separation behavior of five CE methods. The
      results showed that three methods (based on CZE, MEKC, and NACE) were suitable
      for the analysis of basic compounds and three methods (based on CZE and MEKC) for
      the analysis of acidic compounds. For the extraction of analytes from serum and
      urine, a solid-phase extraction (SPE) and a liquid-liquid extraction (LLE) method
      were compared. Both SPE and LLE methods provided clean extracts after extraction
      of the basic compounds from serum and urine. The extracts of acidic compounds
      contained more matrix interferences, especially for urine. The SPE method had
      some advantages compared to LLE, as it lead to cleaner extracts and higher peaks,
      and as it elutes basic and acidic compounds in one fraction. The potentials and
      pitfalls of the various methods for screening purposes in analytical toxicology
      are discussed.

PMID- 11516893
TI  - HPLC of basic drugs on microparticulate strong cation-exchange materials - a
      review.
AB  - Propylsulphonic acid (SCX)-modified silica HPLC columns used with methanol or
      aqueous methanol eluents of appropriate pH and ionic strength can give good
      retention and peak shape for basic drugs. In the system studied, eluent pH
      influenced retention via protonation of basic analytes, the pK(a) of the analyte
      indicating the pH where retention begins to decrease at constant ionic strength.
      At constant pH, retention is inversely proportional to ionic strength for
      protonated bases and quaternary ammonium compounds. The underlying retention
      mechanism appears to be ion-exchange with the SCX moieties, although ionized
      surface silanols may also contribute to retention at higher eluent pH values. In
      capillary electrochromatography (CEC) unprecedented efficiencies, but similar
      selectivity, to that observed in conventional HPLC have been obtained for a
      standard range of basic drugs using Waters Spherisorb S3SCX.SCX-modified silica
      columns can be used in the HPLC of many basic drugs, including some compounds
      that are poorly retained on unmodified silica using methanol-rich eluents. N
      Desalkyl and sulphoxide metabolites are often resolved at an appropriate eluent
      pH. Even analogues differing by a methylene unit in a side-chain remote from a
      basic centre are often resolved. Applications of Waters Spherisorb S5SCX columns
      include HPLC of antimalarials such as chloroquine and quinine, cardioactive
      drugs, for example amiodarone and flecainide, antipsychotics (clozapine,
      olanzapine), and antidepressants (amitriptyline, clomipramine, dothiepin,
      fluoxetine) and their N-desalkyl metabolites. Major practical features of these
      systems are that (i) acidic and neutral compounds are not retained, (ii) solvent
      extracts can be injected directly, and (iii) eluent recycling can be performed
      routinely.

PMID- 11516894
TI  - Fast confirmation of 11-nor-9-carboxy-Delta(9)-tetrahydrocannabinol (THC-COOH) in
      urine by LC/MS/MS using negative atmospheric-pressure chemical ionisation (APCI).
AB  - A fast method using automated solid-phase extraction (SPE) and short-column
      liquid-chromatography coupled to tandem mass-spectrometry (LC/MS/MS) with
      negative atmospheric-pressure chemical ionisation (APCI) has been developed for
      the confirmation of 11-nor-9-carboxy-Delta(9)-tetrahydrocannabinol (THC-COOH) in
      urine samples. This highly specific method which combines chromatographic
      separation and MS/MS-analysis can be used for the confirmation of positive
      immunoassay results with a NIDA cut-off of 15ng/ml. The conjugates of THC-COOH
      were hydrolysed prior to SPE, and a standard SPE was performed using C18-SPE
      columns. No derivatisation of the extracts was needed as in GC/MS analysis, and
      the LC run-time was 6.5min by gradient elution with a retention time of 2.4min.
      Linearity of calibration was obtained in the range between 0 and 500ng/ml
      (correlation coefficient R(2)=0.998). Using linear regression (0-50ng/ml) the
      limit of detection (LOD) was 2.0ng/ml and the limit of quantitation (LOQ) was
      5.1ng/ml; day-to-day reproducibility and precision were tested at 15 and 250ng/ml
      and were 13.4ng/ml+/-3.3% and 255.8ng/ml+/-4.5%, respectively.

PMID- 11516895
TI  - Simultaneous screening and quantitation of 18 antihistamine drugs in blood by
      liquid chromatography ionspray tandem mass spectrometry.
AB  - A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method is presented
      for the simultaneous screening and quantitation of 18 antihistamine drugs in
      blood samples. Sample pretreatment involved liquid-liquid extraction of the basic
      antihistamines followed by a second extraction of the acidic antihistamines. The
      recoveries were 43-113% for basic drugs and 23-66% for acidic drugs. The combined
      extracts were run by LC on C(18) reversed phase column using acetonitrile
      ammonium acetate mobile phase at pH 3.2. The mass spectrometric analysis was
      performed with a triple stage quadrupole mass analyzer. Screening was performed
      using multiple reaction monitoring (MRM) and any compounds tentatively identified
      as antihistamine drugs were then automatedly verified by their Product Ion
      Spectra in a subsequent MS/MS run. Quantitation was based on the MRM data from
      the screening step. In validation tests, the method showed good linearity at the
      relevant concentrations. The attained limits of quantitation varied between
      0.0005 and 0.01mg/l in blood and were lower than the therapeutic concentrations
      (C(max)). The limits for identification by Product Ion Spectra were also lower
      than C(max), except for clemastine, which has exceptionally low concentrations in
      blood. The intra-assay relative standard deviations were better than 10% and the
      inaccuracy varied between 39% for levocabastine and 5% for cyclizine, the
      majority of the values being <20%.

PMID- 11516896
TI  - Sensitive and specific multiresidue methods for the determination of pesticides
      of various classes in clinical and forensic toxicology.
AB  - Original and sensitive multiresidue methods are presented for the detection and
      quantitation, in human biological matrices, of 61 pesticides of toxicological
      significance in human. These methods involved rapid solid-phase extraction using
      new polymeric support (HLB and MCX) OASIS cartridges. Gas chromatography-mass
      spectrometry (GC-MS) was used for volatile (organophosphate, organochlorine,
      phtalimide, uracil) pesticides and liquid chromatography-ionspray-mass
      spectrometry (LC-MS) for thermolabile and polar pesticides (carbamates,
      benzimidazoles). Acquisition was performed in the selected ion monitoring (SIM)
      mode. Extraction recovery varied owing to the nature of pesticides, but was
      satisfactory for all. Limits of detection (LODs) and limits of quantitation
      (LOQs) ranged, respectively, from 2.5 to 20 and from 5 to 50ng/ml. An excellent
      linearity was observed from LOQs up to 1000ng/ml for all the pesticides studied.
      The proposed procedures yielded reproducible results with good inter-assay
      accuracy and precision. A few cases of intoxication are presented to demonstrate
      the diagnostic interest of these methods: in two cases were determined lethal
      concentrations of endosulfan and carbofuran; in four other cases, the procedures
      helped diagnose intoxication with, respectively, parathion-ethyl, the association
      of bromacil and strychnine, bifenthrin and aldicarb.

PMID- 11516897
TI  - An analytical method for the rapid screening of organophosphate pesticides in
      human biological samples and foodstuffs.
AB  - Gas chromatography with nitrogen/phosphorus sensitive detection (GC/PND) and
      electron impact mass spectrometry (GC/MS) with selected ion monitoring provides a
      simple, rapid and sensitive method for the determination of organophosphate
      pesticides (OPs). A selective single-step extraction of 23 different OPs in
      urine, blood, serum and food samples (baby food, soft drinks and instant soups
      suspected of contamination from a blackmailing scare) is described. The OPs were
      extracted with 1ml toluene (with and without addition of mevinphos as internal
      standard), using a 0.7ml aliquot of urine, blood or serum sample. Food samples
      (0.2g) were homogenised with water (0.5ml) before extraction. An amount of
      1microl of the toluene phase (extraction supernatant) was analysed directly by
      GC/PND and GC/MS.The method was validated using spiked human serum. The OPs were
      mixed with serum containing 10mg/ml disodium ethane diamine tetraacetic acid
      disodium salt (EDTA disodium salt) and stored up to 10 days at 4 and -20 degrees
      C, respectively. The recovery rates of OPs in freshly spiked human plasma ranged
      between 50% (dimethoate) and 133% (dialifos). OPs in plasma proved to be stable
      at -20 degrees C. Their levels decreased only slightly after storage at 4 degrees
      C.

PMID- 11516898
TI  - Spectra interference between diquat and paraquat by second derivative
      spectrophotometry.
AB  - A rapid and accurate method, combining solid-phase extraction and second-order
      derivative spectrophotomety approaches, is developed for the simultaneous
      determination of diquat (DQ) and paraquat (PQ) in blood, tissue and urine
      samples. Supernatant resulting from the precipitation of protein (with
      trichloroacetic acid) in plasma and tissue or Amberlite IRA-401 resin treated
      urine are passed through a mini-column packed with Wakogel gel (Silica gel).
      Analytes are then eluted with a non-organic solvent, 0.2mol/l HCl solution
      containing 2mol/l NH(4)Cl. UV spectrum of the eluent in 220-350nm range provides
      effective screen to detect the presence of DQ and/or PQ. In the presence of DQ or
      PQ alone, the analyte present is quantitated by conventional zero- or second
      order derivative spectrophotometry. The calibration curve in the 0.1-5.0mg/l
      range for either analyte obeys Beer's law. When both DQ and PQ are present, their
      concentrations are determined by the peak amplitudes of their respective second
      derivative spectra after the addition of alkaline dithionite reagent.
      Interference is negligible when the DQ/PQ concentration ratio is within the 5.0
      0.2 range. Using a 2-ml of sample size, the detection limits for DQ and PQ in
      plasma are 0.02 and 0.005mg/l. The corresponding detection limits for urine
      samples (10ml sample size) are 0.004 and 0.001mg/l. Recoveries of DQ and PQ in
      triplicate plasma and urine samples spiked with 0.5mg/l of analytes are 93 and
      85%. The precision of the proposed method resulting from triplicate study of
      spiked urine samples varies from 3.2 to 4.6% at 0.5mg/l of DQ and PQ,
      respectively.

PMID- 11516899
TI  - Hydrogen cyanide and carbon monoxide in blood of convicted dead in a polyurethane
      combustion: a proposition for the data analysis.
AB  - Carbon monoxide is a well-known toxic component in fire atmospheres. However, the
      importance of hydrogen cyanide as a toxic agent in fire causalities is under
      discussion. A tragic polyurethane mattress fire provoked death of 35 convicts in
      a prison (Unit I, Olmos, Penitenciary Service of Buenos Aires Province,
      Argentina), in 1990. There is no report of any investigation carried out with
      such a large amount of victims in Argentina. Carboxihemoglobin (COHb) and
      hydrogen cyanide (HCN) were quantified in victims blood to elucidate the cause of
      the death. Saturation of COHb ranged between 4 and 18%, and HCN 2.0-7.2mg/l.
      These latter values were higher than the lethal levels reported in literature.
      Other toxic components routinely measured (ethanol, methanol, aldehydes and other
      volatile compounds) gave negative results on the 35 cases. Neither drugs of abuse
      nor psychotropics were detected. Statistical chi(2) analysis was applied to find
      differences between HCN and COHb concentrations. Saturation of COHb and HCN in
      blood were not independent variables (chi(2)=8.25). Moreover, the ratio COHb/HCN
      was constant (0.47+/-0.04). In order to evaluate the contribution of each toxic
      to the diagnosis, a lethal index was defined for each toxic (LI(CO) and LI(HCN)).
      The most probable cause of death could be inferred by a suitable plot of both
      indexes. The results indicated that death in the 35 fire victims was probably
      caused by HCN, generated during the extensive polyurethane decomposition provoked
      by a rapid increase of temperature.

PMID- 11516900
TI  - Stability of blood carbon monoxide and hemoglobins during heating.
AB  - The effects of heating on hemoglobin (Hb) and carbon monoxide (CO) levels in
      human blood were investigated by in vitro experiments. Head-space gas
      chromatography (HS-GC) using a molecular sieve 5A stationary phase and thermal
      conductivity detection was adopted for the measurement of CO gas, and
      spectrophotometric methods were used for the measurement of various Hb forms,
      protein and heme contents. Deteriorated absorbance spectra were observed for heat
      treated blood samples, and double wavelength spectrophotometry was proven to give
      wrong percent saturation of carboxyhemoglobin content (% CO-Hb). The blood sample
      taken from one fatal fire casualty gave significantly higher % CO-Hb measured
      spectrophotometrically, compared to that by HS-GC. Control blood or purified Hb
      solution, which was saturated with CO in designated extent, was heated in a
      sealed vial. Under the incubation below 54 degrees C, all Hb forms were stable,
      except for oxyhemoglobin (Hb-O(2)), which was partially oxidized to met
      hemoglobin (Met-Hb). In contrast, under the incubation at 65 degrees C, Met-Hb
      was denatured completely to be insoluble, and Hb-O(2) was partially denatured via
      Met-Hb formation. CO-Hb was resistant against heating. The difference of heat
      susceptibility and precipitability among Hb forms resulted in artificial increase
      of % CO-Hb. During heating, spontaneous CO was produced from blood.

PMID- 11516901
TI  - Nitrosylhemoglobin, an unequivocal index of nitric oxide release from
      nitroaspirin: in vitro and in vivo studies in the rat by ESR spectroscopy.
AB  - Electron spin resonance (ESR) spectroscopy was applied for the unequivocal
      detection/quantitation of nitric oxide (NO) as nitrosylhemoglobin (HbFe(II)NO)
      released from nitroaspirin, benzoic acid,2-(acetyloxy)-3-[(nitrooxy)methyl]phenyl
      ester (NCX-4016; NO-ASA), the lead of a new class of nonsteroidal anti
      inflammatory drugs. In both in vitro and in vivo experiments, the paramagnetic
      complex was detected at 100 K in the venous blood of the rat (microwave power, 20
      mW) and characterized by a three-line hyperfine structure with coupling constants
      (A(x) and A(z)) of 17 G at g(x)=2.066 and g(z)=2.009. The kinetics of NO release
      from the drug were first determined in vitro by incubating rat blood with 1 mM NO
      ASA and confirmed by the two-line hyperfine structure obtained with the labeled
      compound ((15)N-NO-ASA). In in vivo studies, the hematic levels of HbFe(II)NO
      were determined after oral (p.o.) and intraperitoneal (i.p.) administration of
      the drug (100 and 200 mg kg(-1)). In p.o. treated animals, the complex was
      detectable at 1 h post-dosing and its formation was maximal at 4-6 h, where the
      antithrombotic activity peaks. In i.p. treated animals, HbFe(II)NO complex peaks
      at the second hour to decline thereafter: in these animals, the ESR technique was
      applied to also detect nitrosylmyoglobin as an index of NO
      diffusion/compartmentalization in myocardial tissue. The results of this study
      emphasize the great potentiality of ESR spectroscopy for the study of the
      release, the metabolic fate and distribution of NO from nitrovasodilators.

PMID- 11516902
TI  - LC fluorescence method for multiple synthetic compounds to rapidly create in vivo
      pharmacokinetic database utilizing 'N-in-One' dosing.
AB  - This manuscript reports development and validation of an assay method in rat
      serum for the simultaneous estimation of C1, C2, and C3, in-house CDRI molecules,
      of the class of aryloxy-substituted aryl-piperazinyl derivatives. The assay was
      applied to determine pharmacokinetic data after simultaneous intravenous
      administration of these three compounds. A high-performance liquid chromatography
      assay method using isocratic elution and fluorescence (excitation, 250 nm;
      emission 350 nm) was developed for simultaneous estimation of all the three
      compounds in rat serum. Linearity was observed between 12.5 and 400 ng/ml for all
      the three compounds in serum. Recoveries were highly consistent over the
      concentration ranges for all the analytes. Variations in the intra- and inter
      batch accuracy and precision were within the acceptable limits of +/-20% at the
      limit of quantitation, whereas at higher concentrations it was +/-15%. A mixture
      of the three compounds was administered intravenously to rats. Blood samples were
      collected over a period of 6 h and analyzed to determine serum levels and
      pharmacokinetics of each compound. The pharmacokinetics of the aforementioned
      three compounds was also determined after individual administration. The results
      obtained in the N-in-One dosing correlated well with discrete dosing of
      compounds. Based on the results obtained, C2 emerges to be the compound with
      appropriate pharmacokinetic parameters. Thus, the N-in-One method is a useful
      method for increasing the throughput to obtain the pharmacokinetic information.

PMID- 11516903
TI  - Sensitive LC determination of piroxicam after in vitro transdermal permeation
      studies.
AB  - A direct, very sensitive, simple and rapid high-performance liquid
      chromatographic (HPLC) method for the determination of piroxicam, with tenoxicam
      as internal standard, has been developed and validated. Samples were
      chromatographed on a 5 microm Scharlau C(18) column. The mobile phase was a
      mixture of acetonitrile-acetic acid 4% (pH 2.8) (45:55, v/v). Detection was at
      354 nm and the run time was 7 min. The limit of detection was 0.025 microg/ml.
      The detector response was found to be linear in the concentration range 0.05-9
      microg/ml. This HPLC assay has been applied to measure the 'in vitro'
      percutaneous permeation of piroxicam through abdominal hairless rat skin, using
      Franz-type diffusion cells, in order to obtain the concentration-time profiles of
      piroxicam.

PMID- 11516904
TI  - Improved LC methods for the determination of diosmin and/or hesperidin in plant
      extracts and pharmaceutical formulations.
AB  - Two improved, simple, selective and sensitive reversed-phase HPLC methods were
      developed for the determination of diosmin and hesperidin simultaneously or
      separately, using external or internal standard techniques, respectively. The
      methods were applied for determination of the diosmin and/or hesperidin in Buchu
      leaves and pharmaceutical dosage forms (three tablets). The methods involved very
      simple efficient extraction procedures, the use of a LiChrosorb RP-18 column, a
      mixture of methanol-water (60:40, v/v) as a mobile phase in an isocratic mode at
      a flow rate of 1.5 ml/min and UV detection at 345 nm. In all HPLC analysis the
      relative standard deviation did not exceed 1.9%. As low as 50 and 25 ng (per
      injection) could be detected in less than 6 min with a high degree of accuracy.
      This is the first report for the determination of the two flavonoids
      simultaneously in Buchu leaf and tablets containing them.

PMID- 11516905
TI  - Influence of viscosity and ionic strength on the reaction kinetics of aldosterone
      and androstendione and their specific antibodies.
AB  - This paper analyses the influence of viscosity and ionic strength on the kinetics
      and equilibrium of the reactions of (125)I labelled androstendione and
      aldosterone with their specific antibodies used in the radioactive immunoassay
      determination of such hormones. Bi-exponential and irreversible kinetics is found
      for androstendione, and single-exponential and reversible ones for aldosterone.
      The results of the viscosity analysis reflect clear negative influence on direct
      reaction rate. Ionic strength excerpts some influence but not in a significant
      way, which suggests that the variation resulting from the effect of the glycerol
      addition is not due to the influence of the dielectric constant of the solutions
      used. The apparent product of the electrical charges is 0.228 for aldosterone,
      and 0.230 and -0.230 for androstendione. Results show diffusive control for both
      cases.

PMID- 11516906
TI  - First-derivative spectrophotometric and LC determination of nifedipine in Brij 96
      based oil/water/oil multiple microemulsions on stability studies.
AB  - A first-derivative spectrophotometric (1D(387)) method was developed for the
      determination of nifedipine in oil/water/oil (O/W/O) multiple microemulsions
      during stability studies. The UV first-derivative spectra were recorded over the
      wavelength range 200-600 nm (Delta lambda=16). The derivative procedure was based
      on the linear relationship between nifedipine concentration and the first
      derivative amplitude at 387 nm. This method was validated and compared with a
      liquid chromatography (LC) procedure used for the quantitative analysis of the
      drug. Both methods showed excellent precision and accuracy with values of 2.09
      and 1.82%, respectively, for the LC method and of 1.53 and 1.64%, respectively,
      for the 1D(387) method. The established linearity range was 5-30 microg ml(-1)
      with r(2) values of 0.9980 and 0.9988 for LC and first-derivative procedures,
      respectively. Nifedipine recoveries from spiked placebos were >95% for both
      methods over the linear range analysed. These methods have been successfully used
      for determining of nifedipine content of multiple microemulsions during stability
      studies, since there was no interference with its decomposition products.

PMID- 11516907
TI  - LC determination of carbamazepine in murine brain.
AB  - A reversed phase HPLC method for the determination of carbamazepine (CBZ) in the
      brain of adult mice is described. CBZ was recovered from murine brain by solvent
      extraction with ethyl acetate and resolved from imipramine (internal standard)
      and brain endogenous material using a Lichrospher RP select B column with a
      linear gradient of acetonitrile (40-80 v/v, 25 min) in ammonium acetate buffer
      (25 mM, pH 4.0) with UV detection at 285 nm. The method is selective,
      reproducible and precise with a limit detection of 45 ng/ml and is suitable for
      the determination of CBZ in murine brain after intra-peritoneal administration.

PMID- 11516908
TI  - LC determination of the anti-ischemic and anti-hypertensive agent CDRI-93/478 in
      rat serum.
AB  - CDRI-93/478 is a potent anti-ischemic and anti-hypertensive agent. This compound
      is in advanced stage of pre-clinical trials. A high-performance liquid
      chromatographic (HPLC) method was developed for the analysis of CDRI-93/478 in
      rat serum, a species used for safety evaluation. The HPLC analysis, applicable to
      1 ml volumes of serum, involved double extraction of serum samples with diethyl
      ether at alkaline pH followed by separation on a spheri-5 cyano column and the
      use of fluorescence detector at excitation wavelength 250 nm and emission
      wavelength 372 nm. The method was sensitive with a limit of quantitation of 10 ng
      ml(-1) in rat serum and the recovery was more than 84%. The linearity was
      satisfactory as indicated by correlation of >0.99, in addition to the visual
      examination of the calibration curves. The precision and accuracy were acceptable
      as indicated by relative standard deviation (R.S.D.) ranging from 1.73 to 9.51%,
      bias values ranging from -7.31 to 8.68%. Moreover, CDRI-93/478 was stable in rat
      serum after being subjected to three freeze-thaw cycles. In-process stability
      evaluation showed the stability of the compound in processed samples lasted up to
      168 h. The assay was found to be sensitive, specific, accurate, precise, and
      reliable for use in pharmacokinetic or toxicokinetic studies.

PMID- 11516909
TI  - Voltammetric determination of nilvadipine in dosage forms and spiked human urine.
AB  - The voltammetric behaviour of nilvadipine was studied adopting direct-current,
      differential-pulse and alternating current polarography. Nilvadipine-being
      nitroderivative-exhibited well-defined cathodic waves over the whole pH range in
      Britton-Robinson buffers. At pH 5, the diffusion-current constant, (Id) was 4.78.
      The current-concentration plots are rectilinear over the range 1.5-20 and 0.2-10
      microg/ml using the direct current and differential pulse-polarographic
      techniques with minimum detectability of 0.05 microg/ml (1.3 x 10(-7) M) using
      the latter technique. The proposed method was applied to commercial capsules
      containing the drug. The percentage recoveries were in agreement with those
      obtained by a reference method. Furthermore, the method was applied to spiked
      human urine, the percentage recovery was 95.54+/-2.137.

PMID- 11516910
TI  - Assay of terfenadine in pharmaceutical formulation and human plasma by adsorptive
      stripping voltammetry.
AB  - The controlled adsorptive accumulation of Zn(II)-terfenadine complex (1:1) onto a
      hanging mercury drop electrode (HMDE) provides the basis for determination of the
      antihistamine drug terfenadine by differential pulse cathodic adsorptive
      stripping voltammetry. The adsorbed Zn(II)-terfenadine complex (1:1) at the HMDE
      developed a stripping voltammetry peak at more negative potential than that of
      the free Zn(II) ions. The peak current was used for the determination of
      terfenadine in pharmaceutical formulation and human plasma in 0.1 mol l(-1)
      sodium perchlorate solution under the optimized conditions (E(acc), -0.5 V;
      t(acc) 360 s; scan rate, 5 mV s(-1) and pulse height 100 mV). The developed peak
      current (i(p)) showed a linear dependence with terfenadine concentration within
      the range of 6 x 10(-8) - 9 x 10(-7) mol l(-1). The recoveries were found 98.97
      99.35%, 99.72-99.02% and 100.58-101.08% with the R.S.D. 0.16-0.27%, 0.25-0.82%
      and 0.44-1.14% in authentic form, pharmaceutical formulations and human plasma,
      respectively. The detection limits were 0.4505 and 0.6115 ng ml(-1) terfenadine
      in pharmaceutical formulations and human plasma, respectively.

PMID- 11516911
TI  - Fast sample preparation for analysis of tablets and capsules: the ball-mill
      extraction method.
AB  - A new ball-mill extraction method for solid dosage forms was developed. It was
      used for tablets, and compared with a conventional (powdering and sonication)
      method applied in pharmaceutical analysis of solid dosage forms. The ball-mill
      sample preparation procedure is both quantitative and fast. No powdering,
      weighing and sonication steps are needed in the sample preparation. The complete
      procedure takes 2 min (milling and extraction) and 5 min (centrifugation),
      respectively, much less than the conventional method in which sample preparation
      takes approximately 45-90 min. The samples are centrifuged in the mill vial,
      which saves time and avoids evaporation of solvent. Stainless steel extraction
      vials with different diameters were fabricated to enable the use of various
      extraction volumes. The extraction recovery was tested using various types of
      tablets (small, large and extended release tablets) with active compounds at low
      and higher concentrations, recoveries were comparable with the conventional
      method. The relative small investment and simplicity of the method makes it
      excellently suited for use in various pharmaceutical (development and quality
      assurance) laboratories.

PMID- 11516912
TI  - Effects of acute exposure to the radiofrequency fields of cellular phones on
      plasma lipid peroxide and antioxidase activities in human erythrocytes.
AB  - Radiofrequency fields of cellular phones may affect biological systems by
      increasing free radicals, which appear mainly to enhance lipid peroxidation, and
      by changing the antioxidase activities of human blood thus leading to oxidative
      stress. To test this, we have investigated the effect of acute exposure to
      radiofrequency fields of commercially available cellular phones on some
      parameters indicative of oxidative stress in 12 healthy adult male volunteers.
      Each volunteer put the phone in his pocket in standby position with the keypad
      facing the body. The parameters measured were lipid peroxide and the activities
      of superoxide dismutase (SOD), total glutathione peroxidase (GSH-Px) and
      catalase. The results obtained showed that the plasma level of lipid peroxide was
      significantly increased after 1, 2 and 4 h of exposure to radiofrequency fields
      of the cellular phone in standby position. Moreover, the activities of SOD and
      GSH-Px in human erythrocytes showed significant reduction while the activity of
      catalase in human erythrocytes did not decrease significantly. These results
      indicate that acute exposure to radiofrequency fields of commercially available
      cellular phones may modulate the oxidative stress of free radicals by enhancing
      lipid peroxidation and reducing the activation of SOD and GSH-Px, which are free
      radical scavengers. Therefore, these results support the interaction of
      radiofrequency fields of cellular phones with biological systems.

PMID- 11516913
TI  - Flow-injection extraction-spectrophotometric method for the determination of
      ranitidine in pharmaceutical preparations.
AB  - The spectrophotometric determination of trace amounts of ranitidine was carried
      out by liquid-liquid extraction using bromothymol blue with a flow system. The
      determination of ranitidine in the range of 1 x 10(-5) - 1 x 10(-4) mol l(-1) was
      possible with a sampling frequency of 40 samples h(-1). The method was
      satisfactorily applied to the determination of ranitidine in pharmaceutical
      preparations and the recovery was quantitative and no interferences from
      excipients were observed.

PMID- 11516914
TI  - LC determination of rofecoxib in bulk and pharmaceutical formulations.
AB  - An isocratic reversed phase-liquid chromatographic (RP-LC) method has been
      developed for the determination and purity evaluation of rofecoxib in bulk and
      pharmaceutical dosage forms using photodiode array detection set at 225 nm. The
      method is simple, rapid and selective. The method is capable of detecting all
      process intermediates and other related compounds, which may be present at trace
      levels in finished products. Hence the method is very useful for process
      monitoring during the production of rofecoxib. Chlorophenyl methyl sulphone has
      been used as internal standard for the quantitative determination of rofecoxib.
      The method is linear in the range of 125-500 microg. The precision for inter- and
      intra-day assay variation of rofecoxib is below 1.6% relative standard deviation
      (R.S.D.). The accuracy determined as relative mean error (R.M.E.) for the intra
      day assay is within +/-2.0%. The drug was extracted from tablets (Vioxx) using
      acetonitrile. The percentage recoveries from dosage forms were ranged from 98.2
      to 102.6.

PMID- 11516915
TI  - LC determination and purity evaluation of nefazodone HCl in bulk drug and
      pharmaceutical formulations.
AB  - A simple, selective and reproducible reversed-phase liquid chromatography (LC)
      method has been developed for the quantitative determination of nefazodone
      hydrochloride (I) in the presence of its related impurities, namely 5-ethyl-4-(2
      phenoxyethyl)-2H-1,2,4-triazol-3-(4H)one (II), 1-(3-chlorophenyl)-4-(3
      chloropropyl) piperazine hydrochloride (III) and 1,1(1)-trimethylene-bis[4-(3
      chlorophenyl) piperazine] hydrochloride (IV). The separation was achieved using
      an Inertsil ODS-3V (250 x 4.6 mm(2)) column and a mobile phase comprising 0.05 M
      KH(2)PO(4) (pH 3.0), acetonitrile and methanol in the ratio 50:40:10 (v/v/v). The
      method has been completely validated and proven to be rugged. The limit of
      detection and limit of quantification for impurities II, III and IV were found to
      be 50, 79 and 91 ng/ml, and 152, 240 and 280 ng/ml, respectively. The intra- and
      inter-day assay precision of the method was within 1.2% relative standard
      deviations. The developed method was applied to the pharmaceutical dosage form
      (Tablet, Serzone-R) and the percentage recoveries ranged from 99.1 to 100.7. The
      percentage recovery of impurities ranged from 96.2 to 108.9. The stability
      studies were performed for nefazodone solution placed on laboratory bench and in
      the refrigerator for 60 days. The method was proved to be stability indicating in
      solution.

PMID- 11516916
TI  - Method for the quantitative analysis of cilostazol and its metabolites in human
      plasma using LC/MS/MS.
AB  - An LC/MS/MS method for the simultaneous determination of cilostazol, a
      quinolinone derivative, and three active metabolites, OPC-13015, OPC-13213, and
      OPC-13217, in human plasma was developed and validated. Cilostazol, its
      metabolites, and the internal standard, OPC-3930 were extracted from human plasma
      by liquid-liquid partitioning followed by solid-phase extraction (SPE) on a Sep
      Pak silica column. The eluent from the SPE column was then evaporated and the
      residue reconstituted in a mixture of methanol/ammonium acetate buffer (pH 6.5)
      (2:8 v/v). The analytes in the reconstituted solution were resolved using
      reversed-phase chromatography on a Supelcosil LC-18-DB HPLC column by an 17.5-min
      gradient elution. Cilostazol, its metabolites, and the internal standard were
      detected by tandem mass spectrometry with a Turbo Ionspray interface in the
      positive ion mode. The method was validated over a linear range of 5.0-1200.0
      ng/ml for all the analytes. This method was demonstrated to be specific for the
      analytes of interest with no interference from endogenous substances in human
      plasma or from several potential concomitant medications. For cilostazol and its
      metabolites, the accuracy (relative recovery) of this method was between 92.1 and
      106.4%, and the precision (%CV) was between 4.6 and 6.5%. During the validation,
      standard curve correlation coefficients equalled or exceeded 0.999 for cilostazol
      and its metabolites. These data demonstrate the reliability and precision of the
      method. The method was successfully cross-validated with an established HPLC
      method.

PMID- 11516917
TI  - Isolation of a 2:1 hydrochlorothiazide-formaldehyde adduct impurity in
      hydrochlorothiazide drug substance by preparative chromatography and
      characterization by electrospray ionization LC-MS.
AB  - Hydrochlorothiazide drug substance (19 lots) from five different manufacturers
      and four different countries of origin (USA, Italy, Hungary, and Croatia) were
      analyzed for the presence of impurities using a gradient elution chromatographic
      system, with acetonitrile-water as the mobile phase. Two known impurities of
      hydrochlorothiazide, 4-amino-6-chloro-1,3-benzenedisulfonamide and
      chlorothiazide, were separated, as well as a late-eluting, unknown, recurring
      impurity. The unknown impurity was isolated by preparative liquid chromatography
      followed by preparative thin-layer chromatography. It was characterized by
      electrospray ionization LC-MS as a 2:1 hydrochlorothiazide-formaldehyde adduct of
      the parent drug substance. The adduct is believed to form through the double
      condensation reaction of hydrochlorothiazide with excess formaldehyde during the
      parent compound's synthesis. The concentration of this impurity ranged from 0.02
      to 1.1% (area%), and was above the 0.1% USP Other Impurities threshold in 16 of
      the 19 lots examined.

PMID- 11516918
TI  - Gas chromatographic assay of diethylcarbamazine in human plasma for application
      to clinical pharmacokinetic studies.
AB  - A sensitive and selective gas chromatography method using flame ionization
      detection was developed for the determination of diethylcarbamazine (DEC) in
      human plasma. DEC and the internal standard, 1-diethylcarbamyl-4-ethyl piperazine
      HCl (E-DEC), were extracted from human plasma after loading onto a conditioned
      C(18) solid phase extraction cartridge, rinsed with water and eluted with
      methanol. After evaporation under a stream of nitrogen and reconstitution in
      methanol, 3 microl were injected onto the GC system. Separation was achieved on a
      A Heliflex(R) AT-35 capillary column (length 30 m, internal diameter 0.32 mm).
      Gas flow rates were: hydrogen, 35 ml/min; carrier gas (helium), 1.5 ml/min, make
      up gas (helium), 25 ml/min; and air 420 ml/min. The retention times of DEC and
      internal standard were approximately 5.5 and 7.28 min, respectively. The GC run
      time was 22 min. The assay was linear in concentration range 100-2000 ng/ml for
      DEC in human plasma. The analysis of quality control samples for DEC (120, 1000,
      2000 ng/ml) demonstrated excellent precision with coefficients of variation of
      4.5,1.3, and 1.6%, respectively (n=6). The method was accurate with all intra-day
      (n=6) and inter-day (n=12) mean concentrations within 4.3% from nominal at all
      quality control sample concentrations. DEC was found to be stable after 3 freeze
      thaw cycles, and with storage at -20 degrees C for 12 weeks. The method is
      currently being used for pharmacokinetic studies of DEC in healthy volunteers.

PMID- 11516919
TI  - Determination of oxamniquine in capsules by HPLC.
AB  - A sensitive, accurate, reliable and easy method was developed for the
      quantification of oxamniquine in capsules using high-performance liquid
      chromatography (HPLC) with UV detection. This technique provided conditions for
      the separation of the active ingredient from the dosage form by extraction in
      methanol. Isocratic reversed phase chromatography was performed using methanol,
      water, and triethanolamine (60:40:0.099, v/v/w) (System C) or methanol,
      acetonitrile, water and formic acid (40:30:30:0.083, v/v/w) (System D) as mobile
      phase, a stainless steel column (125 x 4 mm i.d., 5 microm) filled with
      LiChrospher 100 RP-18 (Merck), column temperature of 28+/-2 degrees C and
      detection at 260 nm. The calibration curves were linear over a wide concentration
      range (1.0-20.0 microg ml(-1) of oxamniquine) to the Systems C and D with good
      correlation factor (0.9990 and 0.9982, respectively). The average content
      obtained were 100.1+/-1.5% (System C) and 102.4+/-0.8% (System D). The presence
      of lactose, starch, magnesium stearate and sodium laurylsulphate did not
      interfere in the results of the analysis. The above findings showed the proposed
      method to be both simple and added advantage of allowing for fast analysis.

PMID- 11516920
TI  - TLC of some free amino acids from sanguine plasma.
AB  - This research presents the results obtained from analysis by thin layer
      chromatography (TLC) of some free amino acids from sanguine plasma samples in the
      different degree progress in maladies: diabetes, renal syndrome and hepatic
      cirrhosis. The chromatograms were evaluated with a Shimadzu CS-9000 dual
      wavelength flying-spot scanner. Better results were obtained in the case of
      hepatic cirrhosis.

PMID- 11516921
TI  - Staff beliefs about addiction treatment.
AB  - In 1999, the National Institute on Drug Abuse established a researcher/provider
      partnership designed to test the effectiveness of research-based innovations in
      community-based treatment settings and facilitate the transfer of those
      innovations throughout the national treatment system. As a preliminary step in
      developing their local Clinical Trials Network, researchers and treatment
      providers within the Delaware Valley Node surveyed 317 staff members concerning
      their beliefs about addiction treatment. More than 80% of respondents supported
      increased use of research-based innovations, 12-step/traditional approaches, and
      spirituality in addiction treatment, while only 39% and 34%, respectively,
      endorsed the increased use of naltrexone and methadone maintenance. Also, 35% of
      respondents indicated that confrontation should be used more, and 46% agreed with
      discharging noncompliant patients. Individuals with more formal training tended
      to be less supportive of confrontation and more supportive of the increased use
      of medications. Implications for the clinical trials and technology transfer are
      discussed.

PMID- 11516922
TI  - Lofexidine versus clonidine in rapid opiate detoxification.
AB  - The aim of the present study is to evaluate lofexidine and clonidine, in an
      accelerated opiate detoxification procedure (3 days), without anaesthesia. Forty
      heroin-dependent individuals were detoxified, evaluating withdrawal symptoms,
      craving levels, mood changes, urine toxicologic screens, and dropout during
      therapy with either (1) clonidine, oxazepam, baclofen, and ketoprofene, with
      naloxone and naltrexone for 3 days (20 subjects) or (2) lofexidine, oxazepam,
      baclofen, and ketoprofene with naloxone and naltrexone for 3 days (20 subjects).
      Both clonidine and lofexidine rapid detoxifications were found effective. The
      subjects treated with lofexidine showed significantly lower levels of withdrawal
      symptoms, fewer mood problems, less sedation and hypotension. No significant
      differences in craving levels, morphine metabolites in urine, or dropout rate
      were evidenced between the two groups. The early use of naltrexone during
      detoxification in combination with either alpha-2-agonist facilitated the
      acceptance for long-term naltrexone treatment. Lofexidine appeared to be more
      useful than clonidine in a 3-day accelerated opiate detoxification, not only to
      counteract withdrawal symptoms, but also in the treatment of dysphoria and mood
      changes. Because lofexidine does not produce hypotension, safe outpatient
      treatment, without hospital support, could be possible.

PMID- 11516923
TI  - A community-based trial of vocational problem-solving to increase employment
      among methadone patients.
AB  - Unemployment remains a common problem among methadone patients. This study
      examined the effectiveness of the Vocational Problem-Solving Skills (VPSS)
      intervention to help unemployed methadone patients obtain employment. METHODS:
      109 patients were randomly assigned to receive 10 sessions of either VPSS (n=62)
      or Interpersonal Problem-Solving (IPS) (n=47). Fourteen counselors from two
      methadone programs were trained to deliver both the VPSS and IPS counseling
      sessions. RESULTS: Overall, 93% (101/109) of the patients completed a 6-month
      follow-up assessment which revealed that 58.6% (34/58) of patients in the VPSS
      condition were employed, whereas 37.2% (16/43) in the comparison condition worked
      (chi-square=4.53, 1 df, p<0.05). However, a multinomial regression equation found
      that the VPSS intervention did not significantly contribute to the prediction of
      employment. Other factors such as longer length of previous work experience, 40
      years of age or older, treatment site, and baseline patient motivation to work
      emerged as significant predictors. CONCLUSION: Although VPSS alone was not a
      strong independent predictor of improved employment functioning, improvements in
      employment functioning were detected at one of the two sites as a function of
      VPSS.

PMID- 11516924
TI  - Characterizing pregnant drug-dependent women in treatment and their children.
AB  - Alcohol and other drug use during pregnancy represents a major public health
      concern. This article characterizes a sample of 240 pregnant opioid- or cocaine
      dependent women enrolled in the initial residential component of a comprehensive
      substance abuse treatment program for pregnant women. Data were collected using
      the Addiction Severity Index, Psychosocial History Form, and Structured Clinical
      Interview for DSM-III-R. Patients' substance use history, psychiatric
      comorbidity, social support network, employability, current and previous
      pregnancies, child custody arrangements, and the father of the current pregnancy,
      are described to assist providers in tailoring treatment to the specific needs of
      this population.

PMID- 11516925
TI  - Exposure therapy in the treatment of PTSD among cocaine-dependent individuals:
      description of procedures.
AB  - An estimated 30% to 50% of cocaine-dependent individuals meet criteria for
      lifetime PTSD. This comorbidity has detrimental effects on clinical presentation,
      and treatment course and outcome. Cocaine dependence is associated with increased
      rates of exposure to trauma, more severe symptoms, higher rates of treatment
      attrition and retraumatization, and greater vulnerability to PTSD when compared
      to other substance use disorders. These associations underscore the need for
      effective treatments that address issues particular to PTSD in a manner tolerable
      to cocaine-dependent individuals. This article describes a manualized
      psychotherapy developed specifically for individuals with PTSD and cocaine
      dependence. Concurrent Treatment of PTSD and Cocaine Dependence (CTPCD) provides
      coping skills training, cognitive restructuring techniques, and relapse
      prevention strategies to reduce cocaine use. In-vivo and imaginal exposure
      therapy techniques are incorporated to reduce PTSD symptom severity. Primary
      treatment goals include psychoeducation specific to the interrelationship between
      PTSD and cocaine dependence, and clinically meaningful reductions in cocaine use
      and PTSD symptomatology. Secondary goals include a reduction in HIV high-risk
      behaviors and improved functioning in associated areas, such as anger and
      negative affect management.

PMID- 11516926
TI  - Exposure therapy in the treatment of PTSD among cocaine-dependent individuals:
      preliminary findings.
AB  - Individuals (n = 39) participated in an outpatient, 16-session individual, manual
      guided psychotherapy designed to treat concurrent PTSD and cocaine dependence.
      Therapy consisted of a combination of imaginal and in-vivo exposure therapy
      techniques to treat PTSD symptoms and cognitive-behavioral techniques to treat
      cocaine dependence. Although the dropout rate was high, treatment completers
      (i.e., patients who attended at least 10 sessions; n = 15) demonstrated
      significant reductions in all PTSD symptom clusters and cocaine use from baseline
      to end of treatment. Significant reductions in depressive symptomatology, as
      measured by the Beck Depression Inventory, and psychiatric and cocaine use
      severity, as measured by the Addiction Severity Index, were also observed. These
      improvements in PTSD symptoms and cocaine use were maintained over a 6-month
      follow-up period among completers. The average pre- to posttreatment effect size
      was 1.80 for PTSD symptoms and 1.26 for drug and alcohol use severity. Baseline
      comparisons between treatment completers and noncompleters revealed significantly
      higher avoidance symptoms, as measured by the Impact of Events Scale, and fewer
      years of education among treatment noncompleters as compared to completers. This
      study provides preliminary evidence to suggest that exposure therapy can be used
      safely and may be effective in the treatment of PTSD in some individuals with
      cocaine dependence. However, the study is limited by the uncontrolled nature of
      the study design, small number of subjects, and high dropout rate.

PMID- 11516927
TI  - Repair of DNA interstrand cross-links.
AB  - DNA interstrand cross-links (ICLs) are very toxic to dividing cells, because they
      induce mutations, chromosomal rearrangements and cell death. Inducers of ICLs are
      important drugs in cancer treatment. We discuss the main properties of several
      classes of ICL agents and the types of damage they induce. The current insights
      in ICL repair in bacteria, yeast and mammalian cells are reviewed. An intriguing
      aspect of ICLs is that a number of multi-step DNA repair pathways including
      nucleotide excision repair, homologous recombination and post
      replication/translesion repair all impinge on their repair. Furthermore, the
      breast cancer-associated proteins Brca1 and Brca2, the Fanconi anemia-associated
      FANC proteins, and cell cycle checkpoint proteins are involved in regulating the
      cellular response to ICLs. We depict several models that describe possible
      pathways for the repair or replicational bypass of ICLs.

PMID- 11516928
TI  - Cisplatin-induced apoptosis in 43-3B and 27-1 cells defective in nucleotide
      excision repair.
AB  - Cisplatin is a highly potent cytotoxic and genotoxic agent used in the
      chemotherapy of various types of tumors. Its cytotoxic effect is supposed to be
      due to the induction of intra- and interstrand DNA cross-links which are repaired
      via the nucleotide excision repair (NER) pathway. Here, we elucidated the
      mechanism of cisplatin-induced cytotoxicity in mutants derived from CHO-9 cells
      defective in NER. We compared 43-3B and 27-1 cells deficient for ERCC1 and ERCC3,
      respectively, with the corresponding wild-type and ERCC1 complemented 43-3B
      cells. It is shown that cells defective in ERCC1 are more sensitive than cells
      defective in ERCC3 with regard to cisplatin-induced reproductive cell death.
      ERCC1 and ERCC3 mutants showed a higher frequency of apoptosis and, to a lesser
      degree, necrosis compared to repair proficient cells. Induction of apoptosis in
      both ERCC1 and ERCC3 defective cells was accompanied by decline in Bcl-2 protein
      level, activation of caspases 8, 9 and 3 and poly(ADP-ribose)polymerase (PARP)
      cleavage. Since the mutant cells are defective in the repair of cisplatin-induced
      DNA lesions, the data demonstrate that non-repaired cisplatin-induced DNA adducts
      act as a trigger of the mitochondrial apoptotic pathway by down-regulation of Bcl
      2 followed by caspase activation.

PMID- 11516929
TI  - Ultraviolet radiation alters the phosphorylation of RNA polymerase II large
      subunit and accelerates its proteasome-dependent degradation.
AB  - It has been shown that ultraviolet (UV) radiation induces the ubiquitination of
      the large subunit of RNA polymerase II (RNAP II-LS) as well as its proteasomal
      degradation. Studies in mammalian cells have indicated that highly phosphorylated
      forms of RNAP II-LS are preferentially ubiquitinated, but studies in
      Saccharomyces cerevisiae have provided evidence that unphosphorylated RNAP II-LS
      is an equally suitable substrate. In the present study, an antibody (ARNA-3) that
      recognizes all forms of RNAP II-LS, regardless of the phosphorylation status of
      its C-terminal domain (CTD), was utilized to evaluate the degradation of total
      cellular RNAP II-LS in human fibroblasts under basal conditions or after UV-C
      (10J/m(2)) irradiation. It was found that UV radiation rapidly shifted the
      phosphorylation profile of RNAP II-LS from a mixture of dephosphorylated and
      phosphorylated forms to entirely more phosphorylated forms. This shift in
      phosphorylation status was not blocked by pharmacologic inhibition of either the
      ERK or p38 pathways, both of which have been implicated in the cellular UV
      response. In addition to shifting the phosphorylation profile, UV radiation led
      to net degradation of total RNAP II-LS. UV-induced degradation of RNAP II-LS was
      also greatly reduced in the presence of the transcriptional and CTD kinase
      inhibitor DRB. Using a panel of protease inhibitors, it was shown that the bulk
      of UV-induced degradation is proteasome-dependent. However, the UV-induced loss
      of hypophosphorylated RNAP II-LS was proteasome-independent. Lastly, UV radiation
      induced a similar shift to all hyperphosphorylated RNAP II-LS in Cockayne
      syndrome (CS) cells of complementation groups A or B (CSA or CSB) when compared
      to appropriate controls. The UV-induced degradation rates of RNAP II-LS were not
      significantly altered when comparing CSA or CSB to repair competent control
      cells. The implications for the cellular UV response are discussed.

PMID- 11516930
TI  - Reduced sensitivity to and ras mutation spectrum of N-ethyl-N-nitrosourea-induced
      thymic lymphomas in adult C.B-17 scid mice.
AB  - Scid mice are defective in the ability to repair DNA double strand breaks and, as
      a consequence, their cells are radiosensitive. Further, they have been shown to
      be prone to develop thymic lymphomas (TLs) after small doses of ionizing
      radiation. Little is known, however, on the role of scid mutation in chemical
      carcinogenesis. To determine if scid mutation increased predisposition to
      chemical carcinogenesis, we examined both the susceptibility of scid mice to N
      ethyl-N-nitrosourea (ENU)-induced lymphomagenesis and the involvement of ras gene
      activation. Adult female mice at 8 weeks of age were given ENU in their drinking
      water at 400 ppm for 2-10 weeks. Contrary to expectations, we observed a two to
      three-fold reduction in TL development in the scid mice. The highest incidence
      was achieved by ENU treatment for 8 weeks for scid and wild-type C.B-17 mice, of
      42 and 85%, respectively (P<0.05). We investigated whether this was attributable
      to the usage of the ras mutation pathway. There was, however, no significant
      difference in the frequency and spectrum of K-ras mutation between the scid and
      wild-type C.B-17 mice. Most of the K-ras mutations were either GGT to GAT
      transition in codon 12 (11/23: 48%) or CAA to CCA transversion in codon 61 (8/23:
      35%) that was independent of scid background. The incidence of N-ras mutation was
      very low. These results indicate that scid mice are less susceptible to ENU
      induced lymphomagenesis and ras gene mutation frequently occurs in both scid and
      wild-type C.B-17 mice.

PMID- 11516931
TI  - Antibiotic sensitivity still prevails in Norwegian blood culture isolates.
AB  - We describe the antimicrobial susceptibility of bacteraemia isolates from Norway.
      From March 1998 to February 1999, four university hospitals covering all parts of
      Norway collected their first 10 isolates each month. Minimal inhibitory
      concentrations were determined for: Enterobacteriaceae (n=192), staphylococci
      (n=89) and Streptococcus pneumoniae (n=69) using the Etest. NCCLS breakpoints
      were used. About 20% of all blood culture isolates in Norway in this period were
      investigated. Compared with countries outside Scandinavia antibiotic sensitivity
      still prevails. Only minor differences in resistance were found between
      participating hospitals, between hospital departments and between hospital- and
      community-acquired pathogens. The prudent use of antibiotics in Norway may
      contribute to the fact that antibiotic resistance still remains low in the most
      common bacterial pathogens causing bloodstream infections.

PMID- 11516932
TI  - Characterization of sparfloxacin-resistant mutants of Staphylococcus aureus
      obtained in vitro.
AB  - A sparfloxacin-susceptible clinical isolate of Staphylococcus aureus was grown in
      increased concentrations of sparfoxacin. The presence of mutations in gyrA, gyrB,
      grlA and grlB genes was analyzed. The primary point mutation was located in the
      gyrA gene (Glu-88 to Lys). Two further mutation steps appeared in the amino acid
      change Ser-80 to Tyr in GrlA. No mutations occurred in the gyrB or grlB genes.
      Efflux pumps involved in the increase of resistance were also found to affect
      norfloxacin and ciprofloxacin. This effect may be related to NorA. An
      overexpression of NorA, may be associated with the increase of the MIC of
      norfloxacin from 32 mg/l to >200 mg/l in the final mutant. The MICs levels of
      sparfloxacin were affected by unknown mechanism.

PMID- 11516933
TI  - Mechanisms other than penicillin-binding protein-2 alterations may contribute to
      moderate penicillin resistance in Neisseria meningitidis.
AB  - Penicillin resistance in Neisseria spp is thought to be generated by the
      interspecies transfer of genetic material from naturally penicillin-resistant,
      commensal species. We examined a series of successive transformants with
      increasing levels of penicillin resistance, obtained by co-cultivation of
      Neisseria meningitidis derivatives with Neisseria polysaccharea. Our results
      suggest that, in addition to the well-known decrease in penicillin affinity of
      penicillin-binding protein-2 (PBP-2), decreased expression of the class 3 porin
      as well as decreased affinity of PBP-1 may contribute to higher level resistance
      of N. meningitidis to penicillin G and other beta-lactam compounds.

PMID- 11516934
TI  - Prevalence of antimicrobial resistance among urinary tract pathogens isolated
      from female outpatients across the US in 1999.
AB  - In the United States, trimethoprim-sulphamethoxazole (TMP-SMX) is the recommended
      first-line treatment for uncomplicated urinary tract infections (UTIs) in
      females, in regions with resistance rates of <10-20%. Unfortunately, current data
      on regional resistance is often not readily available to physicians and regional
      variability in resistance remains largely unknown. This report presents
      antimicrobial susceptibility data for TMP-SMX and three other commonly tested
      antimicrobials organized by state and region to demonstrate current regional
      variability in resistance in the US. In the last quarter of 1999, 5739 fresh
      clinical isolates of Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis
      and Staphylococcus saprophyticus were collected from 202 laboratories throughout
      the US. Susceptibility testing was performed against TMP-SMX, cephalothin,
      nitrofurantoin and ciprofloxacin using broth microdilution. Data were analyzed by
      patient age and specimen source, and by state and region. In the US as a whole,
      resistance to TMP-SMX was 16.8% for E. coli, 7.8% for K. pneumoniae, 12.1% for P.
      mirabilis and 3.0% for S. saprophyticus, but these rates showed considerable
      regional variation. By state, E. coli resistance ranged from 7.4% in Pennsylvania
      to 33.3% in Iowa (among states with > or =50 isolates tested). Regionally,
      resistance for all uropathogens taken together ranged from 8.5% in East South
      Central to 22.8% in West South-Central. Ciprofloxacin demonstrated the broadest
      activity of the antimicrobials tested and was more active than TMP-SMX against
      all pathogens. Resistance to TMP-SMX among E. coli now approaches or exceeds 20%
      in some areas. As resistance among uropathogens reaches clinically significant
      levels in many areas, continued regional surveillance is essential to ensure the
      provision of effective empiric therapy for urinary tract infections.

PMID- 11516935
TI  - Antimicrobial resistance of strains of the Bacteroides fragilis group isolated
      from the intestinal tract of children and adults in Brazil.
AB  - The results of this study show that there is a high frequency of resistant
      species in the Bacteroides fragilis group in the intestinal tract of children and
      adults in Brazil. B. fragilis was not studied. Of the 73 strains examined, B.
      distasonis was the most resistant species to penicillin, cefoxitin, cefotaxime
      and clindamycin. High rates of multiresistance were found, most commonly to
      penicillin and clindamycin (18 of 36 strains). High levels of beta-lactamase
      production were detected in isolates showing high resistance to penicillin and
      multiresistance to the cephamycins, suggesting a widespread dissemination of such
      resistance.

PMID- 11516936
TI  - Antimicrobial susceptibility of potentially pathogenic halophilic vibrios
      isolated from seafood.
AB  - Susceptibility patterns to 27 antimicrobial agents and beta-lactamase production
      were investigated in potentially pathogenic halophilic vibrios from seafood. The
      effect of salinity on the response to the drugs in vitro was also studied. All
      isolates were uniformly sensitive to choramphenicol, imipenem, meropenem but
      resistant to lincomycin. All were highly sensitive to oxolinic acid, trimethoprim
      sulphamethoxazole, doxycycline, flumequine, cefotaxime, nalidixic acid and
      ciprofloxacin. Some strains of V. harveyi, V. alginolyticus and V.
      parahaemolyticus apparently had mechanisms of resistance to several beta-lactam
      antibiotics other than by the production of beta-lactamases. Sixty-nine strains
      produced penicillinase but a low correlation between beta-lactamase activity and
      resistance to beta-lactam antibiotics was noted. The salt concentration affected
      the in vitro susceptibility of halophilic vibrios and the effect of salinity
      depended on both the individual strains and the antimicrobial tested.

PMID- 11516937
TI  - Comparative antimicrobial spectrum and activity of BMS284756 (T-3811, a
      desfluoroquinolone) tested against 656 Enterobacteriaceae, including preliminary
      in vitro susceptibility test comparisons and development.
AB  - BMS284756 (T-3811), a novel des-F(6)-quinolone, was evaluated using isolates of
      Enterobacteriaceae from the SENTRY Antimicrobial Surveillance Program tested by
      Etest (AB BIODISK, Solna, Sweden), reference broth microdilution and disk
      diffusion (5-microg) methods. Ciprofloxacin, levofloxacin, gemifloxacin and
      gatifloxacin were also tested by broth microdilution as comparator antimicrobial
      agents within the same drug class. The 656 isolate collection included species
      from the genera Citrobacter, Enterobacter, Escherichia, Hafnia, Klebsiella,
      Morganella, Pantoea, Proteus, Providencia, Salmonella, and Serratia. BMS284756
      was slightly less active than comparison fluoroquinolones against these isolates
      (MIC(90), 4 mg/l versus 0.06-2 mg/l). However, at a proposed susceptible
      breakpoint of < or =4 mg/l, 90.7% of the isolates processed were susceptible to
      BMS284756, demonstrating an equivalent spectrum of activity to all other agents
      except gemifloxacin (86.6%). In general, isolates requiring >4 mg/l of BMS284756
      for inhibition of growth were also less susceptible to the comparators suggesting
      cross-resistance is common between des-F(6)- and fluoro-quinolones. Excellent
      correlation was observed between broth microdilution MIC results and 5-microg
      disk zone diameters (r=0.94), and between broth microdilution dilution and Etest
      MIC values (r=0.96). In conclusion, BMS284756 has an activity and spectrum
      similar to contemporary fluoroquinolones and in vitro test methods (NCCLS, Etest)
      appear accurate and reproducible

PMID- 11516938
TI  - Multi-resistance to antimicrobial agents for the ten most frequently isolated
      bacterial pathogens.
AB  - Cross-resistance and multi-resistance to selected antibiotics was determined for
      Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Pseudomonas
      aeruginosa, Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus
      faecalis, Streptococcus pneumoniae, Haemophilus influenzae and Moraxella
      catarrhalis. Amikacin-resistant Enterobacteriaceae often showed cross-resistance
      to ss-lactam antibiotics. Only 1% of the Escherichia coli isolates showed
      resistance to more than four antibiotics from a set of seven. This rate was
      higher for other Enterobacteriaceae and there were high levels of cross
      resistance for P. aeruginosa. The cross-resistance of oxacillin with other
      antibiotics is well known in staphylococci. Penicillin-resistant pneumococcal
      isolates were cross-resistant to macrolides. Cross-resistance was only a minor
      problem in H. influenzae and M. catarrhalis. Cross- and multi-resistance are
      important problems for Gram-negative and Gram-positive bacteria but not for
      fastidious bacteria with the exception of penicillin-resistant S. pneumoniae.

PMID- 11516939
TI  - Antimicrobial activity of trifluoromethyl ketones and their synergism with
      promethazine.
AB  - The antimicrobial effects of 30 trifluoromethyl ketones [1-30] were studied on
      various representative bacteria. Of the ketones, 4,4,4-trifluoro-1-phenyl-1,3
      butanedione [10], 1,1,1-trifluoro-3-(4,5-dimethyloxazol-2-yl)-2-propanone [11]
      and 1-(2-benzoxazolyl)-3,3,3-trifluoro-2-propanone [18] were found to exhibit
      potent antibacterial activity against the Gram-positive Bacillus megaterium and
      Corynebacterium michiganese, but not against Gram-negative bacteria such as
      Pseudomonas aeruginosa and Serratia marcescens. Compounds 11 and 18 inhibited the
      Escherichia coli. Compound 18 was also effective against yeasts. The combination
      of promethazine with 18 was significantly synergistic against E. coli strains,
      especially the proton pump deficient mutant. The results suggest that membrane
      transporters are the target of trifluoromethyl ketones. The inhibition was more
      marked in the proton pump deficient E. coli mutant than in the wild type, which
      suggested that the antibacterial effect of trifluoromethyl ketones is partly
      prevented by the proton pump system.

PMID- 11516940
TI  - In vitro antifungal activity of posaconazole against various pathogenic fungi.
AB  - The antifungal activity of posaconazole (SCH56592), a new triazole antifungal,
      against stock cultures and fresh clinical isolates of a wide range of pathogenic
      fungi was compared with that of itraconazole, fluconazole and amphotericin B.
      Posaconazole inhibited growth of all the fungal species tested except Fusarium
      spp. at 1 mg/l or lower concentrations, showing a broad-spectrum antifungal
      activity. The activities of posaconazole for all the fungal species far surpassed
      those of fluconazole and were even superior to those of itraconazole for
      Aspergillus spp. as well as for many other fungal species.

PMID- 11516941
TI  - Comparison of in vitro antifungal activities of topical antimycotics launched in
      1990s in Japan.
AB  - In vitro anti-dermatophyte, anti-Candida albicans and anti-Malassezia furfur
      activities of amorolfine hydrochloride (AMF), terbinafine hydrochloride (TBF),
      butenafine hydrochloride (BTF), neticonazole hydrochloride (NCZ) and ketoconazole
      (KCZ), all of which were introduced for the treatment of dermatomycoses in the
      1990s in Japan, were compared. Although all of the test drugs are classified as
      an ergosterol biosynthesis inhibitor, the antifungal properties were found to be
      different. TBF and BTF exerted extremely potent antifungal activity against
      Trichophyton spp. but not against C. albicans and M. furfur, whilst KCZ and NCZ
      showed potent antifungal activity against C. albicans and M. furfur rather than
      Trichophyton spp. AMF exhibited potent antifungal activity against all of the
      fungal species tested. Fungicidal activities of these antifungal agents against
      T. rubrum were determined by using neutral red staining. The fungicidal
      potentialities correlated with those obtained in the in vitro susceptibility test
      as determined by MICs against dermatophytes. TBF, BTF and AMF exerted more potent
      fungicidal action than NCZ and KCZ.

PMID- 11516942
TI  - Subtyping and antifungal susceptibilities of Candida spp. in the intensive care
      unit of a Greek general hospital.
AB  - This study identified the Candida spp., susceptibility to antifungal agents and
      the prevailing Candida albicans subtypes responsible for infections or
      colonization of 42 patients in the ICU over a 6-month period. Most isolates were
      C. albicans (66.1%) and Candida tropicalis (28.3%) all of which were susceptible
      in vitro to antifungal agents. Subtypes of the C. albicans isolates were
      identified by pulsed field gel electrophoresis Sfi I chromosomal digests. Two
      major C. albicans subtypes were identified, whereas subtype heterogeneity was
      found among strains of Candida glabrata and C. tropicalis. Sfi I PFGE restriction
      patterns were able to discriminate between sub-populations of C. albicans
      isolates, clustering them into distinct, epidemiologically congruous groups.

PMID- 11516943
TI  - Characterization of extended spectrum beta-lactamase-producing Klebsiella
      pneumoniae from Beijing, China.
AB  - Fourteen clinical isolates of Klebsiella pneumoniae with extended-spectrum beta
      lactamases (ESBLs) were detected by the double disk synergy test and the Etest
      ESBL strip. Co-resistances included high MICs for aminoglycosides,
      fluoroquinolones, tetracyclines, and trimethoprim/sulphamethoxazole. Co
      resistance was not observed in five of the 14 strains. These isolates were all
      genetically distinct as determined by the automated ribotyping method.
      Isoelectric focusing documented the presence of multiple beta-lactamases (one to
      four per isolate) with pIs ranging from 5.4 to 8.4. The majority of isolates
      contained beta-lactamases with pI values of 7.6 and 8.4 consistent with SHV-type
      ESBLs and an Amp C enzyme, respectively. Emerging ESBL strains in K. pneumoniae
      compromise the use of agents such as cefotaxime, ceftriaxone, ceftazidime in
      China; leading to the expansion of quality infection control practices and
      formulary management programmes to minimize clonal expansion.

PMID- 11516944
TI  - Antimicrobial susceptibility of community-acquired uropathogens in northern
      Israel.
AB  - In order to study the trends in resistance to first line antimicrobial agents,
      the susceptibility patterns of 8338 community urinary isolates collected during
      1995 were compared with 6692 isolates from 1999. Our data shows that community
      acquired Gram-negative uropathogens remained highly susceptible to ciprofloxacin,
      cefuroxime and amoxycillin/clavulanate with sensitivities of 94, 89 and 83%
      respectively. Nitrofurantoin was shown to be suitable (99% susceptibility rate)
      only for Escherichia coli urinary tract infections. Ampicillin, first generation
      cephalosporins and sulphamethoxazole/trimethoprim could no longer be considered
      first line drugs for empirical treatment of clinically evident urinary tract
      infection because of very high resistant rates. Ampicillin remained a good choice
      for urinary infections caused by enterococci, 98% of the strains being
      susceptible. It was found that 1.25% of the Gram-negative uropathogens isolated
      during 1999 were extended spectrum beta-lactamase producers which suggests that
      this plasmid-encoded trait is finding its way into the community.

PMID- 11516945
TI  - Rate of Staphylococcus aureus nasal carriage in immunocompromised patients
      receiving haemodialysis treatment.
AB  - Specimens from the nose and throat were collected from 28 long-term haemodialysed
      patients. Staphylococcus aureus strains were isolated from sixteen patients who
      been on haemodialysis for over 113 months. Cytokine levels, as well as full blood
      cell differential counts and cell surface antigens were determined in these
      patients. The serum concentration of TGF-beta was significantly higher in
      patients carrying Staphylococcus aureus. CD14 and HLA-DR molecule expression on
      monocytes, as well as NK cell percentage was significantly different in S. aureus
      carriers. Our preliminary results suggest that immune status imbalance in
      haemodialysed patients could be related to the high incidence of S. aureus nasal
      carriage and infections.

PMID- 11516946
TI  - Identification of the NIMA family kinases NEK6/7 as regulators of the p70
      ribosomal S6 kinase.
AB  - BACKGROUND: The p70 S6 kinase, like several other AGC family kinases, requires
      for activation the concurrent phosphorylation of a site on its activation loop
      and a site carboxyterminal to the catalytic domain, situated in a hydrophobic
      motif site FXXFS/TF/Y, e.g.,Thr412 in p70 S6 kinase (alpha 1). Phosphorylation of
      the former site is catalyzed by PDK1, whereas the kinase responsible for the
      phosphorylation of the latter site is not known. RESULTS: The major protein
      kinase that is active on the p70 S6 kinase hydrophobic regulatory site, Thr412,
      was purified from rat liver and identified as the NIMA-related kinases NEK6 and
      NEK7. Recombinant NEK6 phosphorylates p70 S6 kinase at Thr412 and other sites and
      activates the p70 S6 kinase in vitro and in vivo, in a manner synergistic with
      PDK1. Kinase-inactive NEK6 interferes with insulin activation of p70 S6 kinase.
      The activity of recombinant NEK6 is dependent on its phosphorylation, but NEK6
      activity is not regulated by PDK1 and is only modestly responsive to insulin and
      PI-3 kinase inhibitors. CONCLUSION: NEK6 and probably NEK7 are novel candidate
      physiologic regulators of the p70 S6 kinase.

PMID- 11516947
TI  - FhuA-mediated phage genome transfer into liposomes: a cryo-electron tomography
      study.
AB  - BACKGROUND: The transfer of phage genomes into host cells is a well established
      but only dimly understood process. Following the irreversible phage binding to a
      receptor in the bacterial outer membrane, the DNA is ejected from the viral
      capsid and transferred across the bacterial cell envelope. In Escherichia coli,
      the mere interaction of the phage T5 with its outer membrane receptor, the
      ferrichrome transporter FhuA, is sufficient to trigger the release of the DNA
      from the phage capsid. Although the structure of FhuA has been determined at
      atomic resolution, the understanding of the respective roles of phage and
      bacterial proteins in DNA channeling and the mechanisms by which the transfer of
      the DNA is mediated remains fragmentary. RESULTS: We report on the use of cryo
      electron tomography to analyze, at a molecular level, the interactions of T5
      phages bound to FhuA-containing proteoliposomes. The resolution of the three
      dimensional reconstructions allowed us to visualize the phage-proteoliposome
      interaction before and after release of the genome into the vesicles. After
      binding to its receptor, the straight fiber of the phage T5 (the "tip" of the
      viral tail made of pb2 proteins) traverses the lipid bilayer, allowing the
      transfer of its double-stranded DNA (121,000 bp) into the proteoliposome.
      Concomitantly, the tip of the tail undergoes a major conformational change; it
      shrinks in length (from 50 to 23 nm), while its diameter increases (from 2 to 4
      nm). CONCLUSIONS: Taking into account the crystal structure of FhuA, we conclude
      that FhuA is only used as a docking site for the phage. The tip of the phage tail
      acts like an "injection needle," creating a passageway at the periphery of FhuA,
      through which the DNA crosses the membrane. A possible mechanistic scenario for
      the transfer of the viral genome into bacteria is discussed.

PMID- 11516948
TI  - Bistability in the JNK cascade.
AB  - BACKGROUND: Important signaling properties, like adaptation, oscillations, and
      bistability, can emerge at the level of relatively simple systems of signaling
      proteins. Here, we have examined the quantitative properties of one well-studied
      signaling system, the JNK cascade. We experimentally assessed the response of JNK
      to a physiological stimulus (progesterone) and a pathological stress
      (hyperosmolar sorbitol) in Xenopus laevis oocytes, a cell type that is well
      suited to the quantitative analysis of cell signaling. Our aim was to determine
      whether JNK responses are graded (Michaelian) in character; ultrasensitive in
      character, resembling the responses of cooperative enzymes; or bistable and all
      or-none in character. RESULTS: The responses of JNK to both progesterone and
      sorbitol were found to be essentially all-or-none. Individual oocytes had either
      very high or very low JNK activities, with few oocytes possessing intermediate
      levels of JNK activity. Moreover, JNK activation was autocatalytic, indicating
      that the JNK cascade is either embedded in or downstream of a positive feedback
      loop. JNK also exhibited hysteresis, a form of biochemical memory, in its
      response to sorbitol. These findings indicate that the JNK cascade is part of a
      bistable signaling system in oocytes. CONCLUSIONS: In Xenopus oocytes, JNK
      responds to physiological and pathological stimuli in an all-or-none manner. The
      JNK response shows all the hallmarks of a bistable response, including strong
      positive feedback and hysteresis. Bistability is a recurring theme in the
      biochemistry of oocyte maturation and early embryogenesis; the Mos/MEK/p42 MAPK
      cascade also exhibits bistable responses, and the Cdc2/cyclin B system is
      hypothesized to be bistable as well. However, the mechanisms underpinning the
      positive feedback and bistability in the three cases are different, suggesting
      that evolution has repeatedly converged upon bistability as a way of producing
      digital responses.

PMID- 11516949
TI  - Histone variant H2A.Z is required for early mammalian development.
AB  - Fundamental to the process of mammalian development is the timed and coordinated
      regulation of gene expression. This requires transcription of a precise subset of
      the total complement of genes. It is clear that chromatin architecture plays a
      fundamental role in this process by either facilitating or restricting
      transcription factor binding [1]. How such specialized chromatin structures are
      established to regulate gene expression is poorly understood. All eukaryotic
      organisms contain specialized histone variants with distinctly different amino
      acid sequences that are even more conserved than the major core histones [2]. On
      the basis of their highly conserved sequence, histone variants have been assumed
      critical for the function of mammalian chromatin; however, a requirement for a
      histone variant has not been shown in mammalian cells. Mice with a deletion of H1
      degrees have been generated by gene targeting in ES cells, but these mice show no
      phenotypic consequences, perhaps due to redundancy of function [3]. Here we show
      for the first time that a mammalian histone variant, H2A.Z, plays a critical role
      in early development, and we conclude that this histone variant plays a pivotal
      role in establishing the chromatin structures required for the complex patterns
      of gene expression essential for normal mammalian development.

PMID- 11516950
TI  - Noninformative vision improves the spatial resolution of touch in humans.
AB  - Research on sensory perception now often considers more than one sense at a time.
      This approach reflects real-world situations, such as when a visible object
      touches us. Indeed, vision and touch show great interdependence: the sight of a
      body part can reduce tactile target detection times [1], visual and tactile
      attentional systems are spatially linked [2], and the texture of surfaces that
      are actively touched with the fingertips is perceived using both vision and touch
      [3]. However, these previous findings might be mediated by spatial attention [1,
      2] or by improved guidance of movement [3] via visually enhanced body position
      sense [4--6]. Here, we investigate the direct effects of viewing the body on
      passive touch. We measured tactile two-point discrimination thresholds [7] on the
      forearm while manipulating the visibility of the arm but holding gaze direction
      constant. The spatial resolution of touch was better when the arm was visible
      than when it was not. Tactile performance was further improved when the view of
      the arm was magnified. In contrast, performance was not improved by viewing a
      neutral object at the arm's location, ruling out improved spatial orienting as a
      possible account. Controls confirmed that no information about the tactile
      stimulation was provided by visibility of the arm. This visual enhancement of
      touch may point to online reorganization of tactile receptive fields.

PMID- 11516951
TI  - Effects of DNA nonhomologous end-joining factors on telomere length and
      chromosomal stability in mammalian cells.
AB  - DNA repair by nonhomologous end-joining (NHEJ) relies on the Ku70:Ku80
      heterodimer in species ranging from yeast to man. In Saccharomyces cerevisiae and
      Schizosaccharomyces pombe, Ku also controls telomere functions. Here, we show
      that Ku70, Ku80, and DNA-PKcs, with which Ku interacts, associate in vivo with
      telomeric DNA in several human cell types, and we show that these associations
      are not significantly affected by DNA-damaging agents. We also demonstrate that
      inactivation of Ku80 or Ku70 in the mouse yields telomeric shortening in various
      primary cell types at different developmental stages. By contrast, telomere
      length is not altered in cells impaired in XRCC4 or DNA ligase IV, two other NHEJ
      components. We also observe higher genomic instability in Ku-deficient cells than
      in XRCC4-null cells. This suggests that chromosomal instability of Ku-deficient
      cells results from a combination of compromised telomere stability and defective
      NHEJ.

PMID- 11516952
TI  - Securin is not required for cellular viability, but is required for normal growth
      of mouse embryonic fibroblasts.
AB  - Sister chromatid separation depends on the release of cohesion by the activity of
      Esp1, a member of the caspase family [1, 2]. In budding yeast, Esp1p is kept
      inactive by its association with Pds1p, until the onset of anaphase, when Pds1p
      is ubiquitinated by the APC/Cdc20 complex [3--5] and subsequently degraded by the
      26S proteasome. Pds1 is not an essential gene in budding yeast, but is required
      for cell cycle arrest prior to anaphase in response to the disruption of spindle
      structures [6, 7]. Thus, Pds1 mutant yeast cells display precocious sister
      chromatid separation in the presence of nocodazole [6]. Mammalian orthologs of
      yeast Esp1 and Pds1, separin and securin, have been identified [8], and, as
      anticipated, a nondegradable mutant form of securin inhibits sister separation
      when added to mitotic Xenopus egg extracts [8]. Securin was also independently
      identified as PTTG (pituitary tumor transforming gene), a gene overexpressed in
      pituitary tumors [9]. The relationship between its overexpression in tumors and
      its control of sister chromatid cohesion remains ill defined. To explore securin
      function in mammals, we took a targeted gene disruption approach in mice. Here,
      we report that securin is neither essential for cell viability nor required for
      spindle checkpoint function, and mice lacking securin are viable and apparently
      normal, but mouse embryonic fibroblasts lacking securin grow abnormally in
      culture.

PMID- 11516953
TI  - The medaka rs-3 locus required for scale development encodes ectodysplasin-A
      receptor.
AB  - The bodies of most teleost fish species are covered with specialized
      subepithelial structures known as scales. The scale is an epithelial appendage
      that differentiates from the dermal mesenchyme. Mammals, on the other hand, have
      no scales, but instead their bodies are covered with hair. Although their
      appearances are quite different, scales and hair can be considered structurally
      similar in that both of them are epithelial appendages distributed over the body
      surface in an orderly pattern. This analogy suggests that they may have the same
      evolutionary origin. But, to date, no molecular evidence has been presented that
      links scales and hair. A mutation at the rs-3 locus of medaka (Oryzias latipes)
      leads to almost complete loss of scales. We demonstrated that the rs-3 locus
      encodes ectodysplasin-A receptor (EDAR), which is required for the initiation of
      hair development in mammals. We identified a novel transposon inserted in the
      first intron of EDAR, which causes aberrant splicing. This work shows that EDAR
      is required for scale development in fish and suggests that it is an
      evolutionarily conserved molecule that is required for the development of
      epithelial appendages in vertebrates.

PMID- 11516954
TI  - Analysis of an essential requirement for the poly(A) binding protein function
      using cross-species complementation.
AB  - Poly(A) binding protein (PABP) is an essential, well-conserved, multifunctional
      protein involved in translational initiation, mRNA biogenesis, and degradation [1
      -5]. We have used a cross-species complementation approach to address the nature
      of the essential requirement for PABP in yeast. The expression of Pab3p, a member
      of the Arabidopsis thaliana PABP multigene family, rescues the lethal phenotype
      associated with the loss of the yeast Pab1p. However, Pab3p neither protects the
      mRNA 5' cap from premature removal, nor does it support poly(A)-dependent
      translational initiation or the synergistic enhancement of translation by the
      poly(A) tail and 5' cap in yeast. However, Pab3p corrects the temporal lag prior
      to the entry of the mRNA into the degradation pathway characteristic of pab1
      Delta yeast strains. Furthermore, this lag correction by Pab3p requires Pan3p, a
      subunit of poly(A) nuclease, an enzyme involved in the mRNA 3'-end processing.
      Importantly, the substitution of Pab3p for the yeast Pab1p is synthetically
      lethal with the PAN3 gene deletion. These results show that the function of PABP
      in mRNA biogenesis alone could be sufficient to support cell viability in yeast.

PMID- 11516955
TI  - Steering with the head. the visual strategy of a racing driver.
AB  - We studied the eye movements of a racing driver during high-speed practice to see
      whether he took in visual information in a different way from a normal driver on
      a winding road [1, 2]. We found that, when cornering, he spent most of the time
      looking close to, but not exactly at, the tangent points on the inside edges of
      the bends. Each bend was treated slightly differently, and there was a highly
      repeatable pattern to the way the track edge was viewed throughout each bend. We
      also found a very close relationship between the driver's head direction and the
      rate of rotation of the car 1 s later. We interpret these observations as
      indicating that the driver's gaze is not driven directly by tangent point
      location, as it is in ordinary driving. Instead, we propose that his head
      direction is driven by the same information that he uses to control steering and
      speed, namely his knowledge of the track and his racing line round it. If he
      directs his head at an angle proportional to his estimate of car rotation speed,
      this will automatically bring his head roughly into line with the tangent points
      of the bends. From this standardized position, he can use the expected movements
      of the tangent points in his field of view to verify, and if necessary modify,
      his racing line during the following second.

PMID- 11516956
TI  - Role for cyclin-dependent kinase 2 in mitosis exit.
AB  - Mitosis requires cyclin-dependent kinase (cdk) 1-cyclin B activity [1]. Exit from
      mitosis depends on the inactivation of the complex by the degradation of cyclin B
      [2]. Cdk2 is also active during mitosis [3, 4]. In Xenopus egg extracts, cdk2 is
      primarily in complex with cyclin E, which is stable [5]. At the end of mitosis,
      downregulation of cdk2-cyclin E activity is accompanied by inhibitory
      phosphorylation of cdk2 [6]. Here, we show that cdk2-cyclin E activity maintains
      cdk1-cyclin B during mitosis. At mitosis exit, cdk2 is inactivated prior to cdk1.
      The loss of cdk2 activity follows and depends upon an increase in protein kinase
      A (PKA) activity. Prematurely inactivating cdk2 advances the time of cyclin B
      degradation and cdk1 inactivation. Blocking PKA, instead, stabilizes cdk2
      activity and inhibits cyclin B degradation and cdk1 inactivation. The
      stabilization of cdk1-cyclin B is also induced by a mutant cdk2-cyclin E complex
      that is resistant to inhibitory phosphorylation. P21-Cip1, which inhibits both
      wild-type and mutant cdk2-cyclin E, reverses mitotic arrest under either
      condition. Our findings indicate that the proteolysis-independent downregulation
      of cdk2 activity at the end of mitosis depends on PKA and is required to activate
      the proteolysis cascade that leads to mitosis exit.

PMID- 11516957
TI  - Stem cells fuel bitter ethical divisions.

PMID- 11516958
TI  - Alarm as males face reproductive shun.

PMID- 11516959
TI  - Cautious welcome for GM crops.

PMID- 11516960
TI  - A novel family of predicted retroviral-like aspartyl proteases with a possible
      key role in eukaryotic cell cycle control.

PMID- 11516961
TI  - Guard cells.

PMID- 11516962
TI  - Endochondral ossification: a delicate balance between growth and mineralisation.

PMID- 11516963
TI  - Wnt signalling: antagonistic Dickkopfs.
AB  - Dickkopf proteins are secreted antagonists of the Wnt cell signalling molecules,
      which have a novel mode of action. Dickkopf1 binds to the LRP5/6 Wnt co-receptor
      and prevents the formation of active Wnt--Frizzled--LRP5/6 receptor complexes,
      thus blocking the canonical Wnt--beta-catenin pathway.

PMID- 11516964
TI  - Protein kinases: getting NEKed for S6K activation.
AB  - The 70/85 kDa ribosomal protein S6 kinase is regulated through the concerted
      actions of multiple phosphatases and kinases. A newly identified S6 kinase
      kinase, NEK6, appears to provide the penultimate activation step.

PMID- 11516965
TI  - Cell polarity: a tale of two Ts.
AB  - The microtubule cytoskeleton plays an important role in cell polarity. Central to
      this process in fission yeast is tea1p, a marker of polarized cell growth that is
      delivered to the cell surface in a microtubule-dependent fashion. Recent studies
      suggest that the actin-binding protein bud6p may be a tea1p effector.

PMID- 11516966
TI  - Decision making: the two stages of neuronal judgement.
AB  - A recent study of how a monkey's frontal cortex responds when decisions are made
      more difficult has characterised the two distinct stages which turn sensory
      evidence into a command for action.

PMID- 11516967
TI  - Translational repression: not just a Puf of smoke.
AB  - Proteins containing Puf domains interact with cofactors to form complexes that
      bind RNAs and control diverse developmental events. Recent studies have shed
      light on how the Puf family of proteins regulates mRNA activity.

PMID- 11516968
TI  - Cell polarity: connecting to the cortex.
AB  - A GTPase module controls growth-site selection in budding yeast cells. The GDP-
      GTP exchange factor of this module, Bud5, has now been localized to sites of cell
      division and shown to interact with a transmembrane protein that marks these
      sites.

PMID- 11516969
TI  - Cognitive neuroscience: early learning centres.
AB  - Learning leads to neural changes often considered to be driven by 'smart' areas
      of the brain. A recent study of the cellular changes that underlie perceptual
      learning has found that plasticity in the primary visual cortex V1 is necessary
      for learning and the changes that correlate with learning are more complex than
      one might expect.

PMID- 11516970
TI  - Vertebrate development: Et in Arkadia.
AB  - The similarities in organiser formation in Xenopus and mouse embryos have
      remained elusive. Recent evidence suggests a common mechanism, in which an
      intracellular protein, Arkadia, is required for formation of the mouse organiser
      and potentiates the effects of the signalling protein Nodal.

PMID- 11516971
TI  - From stones to bones: the biology of ClC chloride channels.
AB  - Chloride (Cl(-)) is the most abundant extracellular anion in multicellular
      organisms. Passive movement of Cl(-) through membrane ion channels enables
      several cellular and physiological processes including transepithelial salt
      transport, electrical excitability, cell volume regulation and acidification of
      internal and external compartments. One family of proteins mediating Cl(-)
      permeability, the ClC channels, has emerged as important for all of these
      biological processes. The importance of ClC channels has in part been realized
      through studies of inherited human diseases and genetically engineered mice that
      display a wide range of phenotypes from kidney stones to petrified bones. These
      recent findings have demonstrated many eclectic functions of ClC channels and
      have placed Cl(-) channels in the physiological limelight.

PMID- 11516972
TI  - PPARgamma and inflammatory bowel disease: a new therapeutic target for ulcerative
      colitis and Crohn's disease.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) is a nuclear
      receptor that is known to play a central role in adipocyte differentiation and
      insulin sensitivity. Through work in several animal models of intestinal
      inflammation, it is now recognized that PPARgamma also inhibits tissue injury
      associated with immune activation. These studies point to PPARgamma as a novel
      anti-inflammatory mediator with broad therapeutic potential.

PMID- 11516973
TI  - The PPARs 2001: it's not over 'til the fat lady sings. 4-10 February 2001.

PMID- 11516974
TI  - Angiogenesis and chronic disease. 24-29 April 2001.

PMID- 11516975
TI  - Bowel disease gets the Nod.

PMID- 11516976
TI  - Shedding light on endometrial cancer.

PMID- 11516977
TI  - Beneficial autoimmunity in traumatic brain injury.

PMID- 11516993
TI  - How do neurons die in neurodegenerative diseases?
AB  - Given that neurons are post-mitotic cells, their life span is generally long
      enough to reach that of humans. However, sometimes neurons die without
      recognizable causes, as a result of a process called neurodegeneration. Apart
      from when gene mutations can be correlated with disease, it is difficult to
      pinpoint molecules that are responsible for neuronal death. Therefore, neurons
      living in a 'sick state' for many years might reveal important information about
      neuronal death. Systematic and extensive single-neuron analysis of 'sick' neurons
      is expected to provide clues to the mechanisms of neurodegeneration. Moreover,
      the elimination of putative triggering and promoting factors involved in
      neurodegenerative disease might prevent disease progression.

PMID- 11516994
TI  - Hypoxia-inducible factor 1: oxygen homeostasis and disease pathophysiology.
AB  - Hypoxia-inducible factor 1 (HIF-1) activates transcription of genes encoding
      proteins that mediate adaptive responses to reduced oxygen availability. The HIF
      1beta subunit is constitutively expressed, whereas the HIF-1alpha subunit is
      subject to ubiquitination and proteasomal degradation, a process that is
      inhibited under hypoxic conditions. Recent data indicate that HIF-1 plays major
      roles in the prevention of myocardial and cerebral ischemia and in the
      pathogenesis of pulmonary hypertension and cancer. Modulation of HIF-1 activity
      by genetic or pharmacological means could provide a novel therapeutic approach to
      these common causes of mortality.

PMID- 11516995
TI  - Yellow fever vector live-virus vaccines: West Nile virus vaccine development.
AB  - By combining molecular-biological techniques with our increased understanding of
      the effect of gene sequence modification on viral function, yellow fever 17D, a
      positive-strand RNA virus vaccine, has been manipulated to induce a protective
      immune response against viruses of the same family (e.g. Japanese encephalitis
      and dengue viruses). Triggered by the emergence of West Nile virus infections in
      the New World afflicting humans, horses and birds, the success of this
      recombinant technology has prompted the rapid development of a live-virus
      attenuated candidate vaccine against West Nile virus.

PMID- 11516996
TI  - The calpain family and human disease.
AB  - The number of mammalian calpain protease family members has grown to 14 on last
      count. Overactivation of calpain 1 and calpain 2 (and their small subunit) has
      long been tied to acute neurological disorders (e.g. stroke and traumatic brain
      injury) and recently to Alzheimer's disease. Loss-of-function mutations of the
      calpain 3 gene have now been identified as the cause of limb-girdle muscular
      dystrophy 2A. Calpain 10 was recently identified as a susceptibility gene for
      type 2 diabetes, whereas calpain 9 appears to be a gastric cancer suppressor.
      This review describes our current understanding of the calpain family members and
      their mechanistic linkages to the aforementioned diseases as well as other
      emerging pathological conditions.

PMID- 11516997
TI  - Clinical and genetic heterogeneity in nemaline myopathy--a disease of skeletal
      muscle thin filaments.
AB  - The term nemaline myopathy (NM) encompasses a heterogeneous group of disorders of
      primary skeletal muscle weakness characterized by the presence of nemaline rods
      in muscles of affected individuals. Disease severity is variable and
      unpredictable, with prognosis ranging from neonatal death to almost normal motor
      function. Recent advances in the identification of NM disease genes demonstrate
      that NM is a disease of the skeletal muscle sarcomere and, in particular, of the
      thin filaments. These findings are starting to alter the approach that
      neurologists and geneticists take to diagnosing and counseling patients with NM,
      and could lead to insights into specific directed therapies in the future.

PMID- 11516998
TI  - Disease model: familial adenomatous polyposis.
AB  - Mutations in the APC gene are responsible for familial adenomatous polyposis
      (FAP) and for the majority of sporadic colorectal cancers. The establishment of
      genotype-phenotype correlations in FAP is often complicated by the great clinical
      variability observed among carriers of the same APC mutation even within the same
      kindred. This variability is likely to arise from the interaction of genetic and
      environmental modifying factors, the dissection of which ideally requires the
      employment of mouse models where the effects of specific Apc mutations are
      analyzed in an inbred, homogeneous genetic background and a controlled
      environment. The availability of different Apc mouse models allows not only the
      establishment of more precise genotype-phenotype correlations but has also
      provided very important clues for the understanding of the function of APC in
      homeostasis and tumorigenesis. Also, the close phenotypic resemblance to the
      human disease makes these mice unique preclinical models to test chemopreventive
      and therapeutic interventions.

PMID- 11516999
TI  - Disease model: hyperinsulinemia and insulin resistance. Part B--polygenic and
      other animal models.
AB  - Deficiency of leptin or its receptor produces hyperinsulinemia with marked
      obesity. Paradoxically, severe insulin resistance also accompanies lipodystrophy.
      Animal models of these contrasting conditions have enabled us to observe the
      profound and complicated aspects of the underlying pathologies. In addition,
      conventional polygenic rodents with known genetic backgrounds, such as the
      spontaneously hypertensive rat and the Goto-Kakisaki rat, have also been used to
      investigate these abnormalities.

PMID- 11517000
TI  - Pictures in molecular medicine: three-dimensional visualization of intravascular
      tumor cells in mice.

PMID- 11517001
TI  - Expression and secretion of activin A: possible physiological and clinical
      implications.

PMID- 11517002
TI  - Incidentaloma, glucocorticoid excess and low bone mineral density: a coincidence?

PMID- 11517003
TI  - Bone loss determined by quantitative ultrasonometry correlates inversely with
      disease activity in patients with endogenous glucocorticoid excess due to adrenal
      mass.
AB  - OBJECTIVE: Glucocorticoid excess is widely recognized as one of the most
      important causes of bone loss. The mechanism of glucocorticoid-induced
      osteoporosis is presumably multifactorial, and consists of the loss of organic
      and non-organic compounds. Efforts have been made to develop simple physical
      methods for the assessment of bone tissue for the screening of subjects at high
      risk of osteoporosis, without the use of radioactive sources or ionizing
      radiation. Quantitative ultrasonometry (QUS) has been suggested as a useful
      method for monitoring patients undergoing glucocorticoid therapy, which is the
      most common cause of glucocorticoid excess. QUS appears to detect more structural
      bone changes than the traditional methods and allows assessment of bone density
      and elasticity, both characteristics influenced by organic and non-organic bone
      compounds. However, the use of QUS has not yet been extensively investigated in
      subjects with endogenous cortisol excess. The aim of this study was to evaluate
      the usefulness and predictive power of QUS in assessing bone loss in subjects
      with differing degrees of endogenous cortisol excess due to adrenal mass. DESIGN:
      Thirty-four patients (20 women and 14 men) aged between 21 and 59 years were
      evaluated; fifteen (9 women and 6 men; median age, 42 years) were affected by
      overt Cushing's syndrome (CS) and nineteen (11 women and 8 men; median age, 44
      years) by subclinical CS, defined as lacking clinical signs of hormone excess
      despite the presence of at least two abnormalities in hypothalamic-pituitary
      adrenal axis function, as assessed by routine endocrine tests. All women included
      were eumenorrhoic. METHODS: QUS measurement of amplitude-dependent speed of sound
      was performed on the 2nd to 5th proximal phalanges of the non-dominant hand using
      a DBM Sonic 1200R bone profiler (Igea S.r.l, Italy). The results were compared
      with bone density assessed on lumbar vertebrae (L1-L4) and femoral neck sites by
      dual-energy X-ray absorptiometry (DEXA). RESULTS: A strongly significant bone
      loss was detected by finger QUS measurement when the patients were considered
      either all together or as two subgroups (P<0.001, all). The bone density decrease
      in the fingers was similar to that found at the lumbar spine and femoral neck by
      the DEXA technique. Lumbar and finger Z-scores correlated inversely with 24 h
      urinary free cortisol (UFF) excretion (P<0.01, both). Finger Z-scores also
      correlated inversely with the estimated duration of subclinical CS (P<0.05).
      Concerning disease activity, only UFF was confirmed by multivariate analysis to
      be an independent factor influencing bone loss (P<0.05). A positive correlation
      between the results of the two techniques was found in controls (P<0.05) but not
      in patients. The lack of correlation between the two techniques in patients can
      probably be attributed to the different parameters of bone alteration measured by
      the techniques. CONCLUSIONS: The detection of bone loss in subclinical CS similar
      to that in overt CS suggests that all subjects with endogenous cortisol excess
      should be evaluated for bone mass. QUS measurement appears to be a reliable,
      radiation-free, simple and fast tool for the identification of bone alteration in
      subjects with endogenous cortisol excess.

PMID- 11517004
TI  - A novel germline mutation in the TSH receptor gene causes non-autoimmune
      autosomal dominant hyperthyroidism.
AB  - OBJECTIVE: Clinical and genetic investigations were undertaken in a case of
      familial hyperthyroidism, with onset of thyrotoxic symptoms varying between
      childhood/adolescence. METHODS: Automatic sequence analysis was carried out of
      the TSH receptor (TSHR) gene. Functional studies were undertaken of mutant TSHR
      in transient expression experiments in COS-7 cells including the evaluation of
      cAMP accumulation and of protein expression by flow cytometry, as well as the
      calculation of specific constitutive activity (SCA). RESULTS: In four affected
      cases, the age of onset of thyrotoxic manifestations of non-autoimmune origin
      varied between 5 and 18 years. The disease transmission was typically autosomal
      dominant. TSHR gene sequence revealed the presence of a germline heterozygous
      substitution at codon 597 leading to the novel mutation V597F. This residue is
      located in the 5th transmembrane domain of the receptor protein in a critical
      region for membrane targeting and signal transduction. Functional studies of the
      V597F mutant indicate an 11-fold increase in SCA, associated with a reduction in
      receptor protein expression on the cytoplasmic membrane. CONCLUSIONS: Description
      was made of a family with non-autoimmune autosomal dominant hyperthyroidism
      carrying a novel mutation of TSHR leading to the increment in specific
      constitutive activity. Factors that may influence the clinical expression of TSHR
      germline mutations are discussed.

PMID- 11517005
TI  - Development and psychometric properties of a disease-specific quality of life
      questionnaire for adult patients with growth hormone deficiency.
AB  - BACKGROUND: Adults with growth hormone (GH) deficiency (GHD) may experience
      physical and psychological disturbances, which can affect their quality of life
      (QOL). OBJECTIVES: To develop and validate a disease-specific module from the
      previously published QOL measure Questions on Life Satisfaction Modules (QLS(M)):
      the QLS(M)-H that specifically addressed the needs of patients with
      hypopituitarism. A second aim was for the questionnaire to be applicable across
      different cultural backgrounds in order to evaluate the efficacy of therapy in
      large, international clinical trials, thus providing additional clinical
      endpoints for these studies. DESIGN: A preliminary German language version of the
      QLS(M)-H was developed from 26 semi-structured interviews of adults with GHD. The
      questionnaire was then independently translated into five other languages and
      applied in open, non-controlled, multicentre, longitudinal studies to patient
      (n=717) and normative populations (n=2700). METHODS: A revised, nine-item version
      of the questionnaire was developed, based on previously defined criteria, and was
      evaluated for reliability and validity. Sensitivity to detect changes after GH
      replacement was also assessed. RESULTS: The 16 items of the preliminary
      questionnaire were reduced to nine items on the basis of the correlation of
      items/factors from initial patient interviews. Psychometric analysis revealed the
      reliability of the nine-item scale. The Cronbach's alpha scores ranged from 0.81
      to 0.89 and the test-retest correlations ranged from 0.76 to 0.88, all of which
      indicate reliability over time. Mean scores increased significantly during GH
      replacement therapy, with observed changes greater than those seen with the non
      specific modules of the QLS(M), indicating the sensitivity of the scale.
      CONCLUSIONS: The QLS(M)-H questionnaire is concise, easy to complete, and can be
      effectively applied across different cultural backgrounds. Psychometric
      evaluation of the questionnaire reveals that it is a valid, reliable and
      sensitive tool useful for assessing impaired life satisfaction in adult patients
      with GHD and also for monitoring the efficacy of GH therapy.

PMID- 11517006
TI  - Enhancement of the peripheral sensitivity to growth hormone in adults with GH
      deficiency.
AB  - OBJECTIVE: Adults with severe GH deficiency (GHD) need recombinant human growth
      hormone (rhGH) replacement to restore body composition, structure functions and
      metabolic abnormalities. The optimal rhGH dose for replacement has been
      progressively reduced to avoid side effects. The aim of the present study was to
      define the minimal rhGH dose able to increase both IGF-I and IGF binding protein
      (BP)-3 levels in GHD and to verify the possible change in GH sensitivity. DESIGN
      AND PATIENTS: To this goal, we studied the effect of 4-day treatment with 3 rhGH
      doses (1.25, 2.5 and 5.0 microg/kg/day) on IGF-I and IGFBP-3 levels in 25
      panhypopituitary adults with severe GHD (12 males and 13 females, age: 44.5+/-3.0
      years, body mass index (BMI): 27.0+/-0.9 kg/m(2)) and 21 normal young adult
      volunteers (NV, 12 males and 9 females, age: 30.5+/-2.0 years, BMI: 20.8+/-0.5
      kg/m(2)). RESULTS: Basal IGF-I and IGFBP-3 levels in GHD were lower (P<0.001)
      than in NV. In NV the 1.25 microg/kg dose of rhGH did not modify IGF-I levels.
      The dose of 2.5 microg/kg rhGH significantly increased IGF-I levels in men
      (P<0.001) but not in women, while the 5.0 microg/kg dose increased IGF-I levels
      in both sexes (P<0.001). IGFBP-3 levels were not modified by any of the
      administered rhGH doses. In GHD patients, all rhGH doses increased IGF-I levels
      12 h after both the first (P<0.01) and the fourth rhGH dose (P<0.001). At the end
      of treatment percentage increases in IGF-I were higher (P<0.001) in GHD patients
      than in NV. In contrast with NV, in GHD patients the IGF-I response to short-term
      stimulation with rhGH was independent of gender. Moreover, GHD patients showed
      increases in IGFBP-3 after the fourth administration of both 2.5 and 5.0
      microg/kg rhGH. CONCLUSION: The results of the present study demonstrate that the
      minimal rhGH dose able to increase IGF-I and IGFBP-3 levels in GHD patients is
      lower than in normal subjects, at least after a very short treatment. This
      evidence suggests an enhanced peripheral GH sensitivity in GH deprivation.

PMID- 11517007
TI  - Changes in tumor necrosis factor-alpha system and insulin sensitivity during an
      exercise training program in obese women with normal and impaired glucose
      tolerance.
AB  - OBJECTIVE: Tumor necrosis factor-alpha (TNFalpha) plays an important role in the
      pathogenesis of insulin resistance and type 2 diabetes. Plasma levels of the
      soluble (s) fractions of TNFalpha receptors, especially sTNFR2, are good
      indicators of TNFalpha system activation in obesity. The aim of the present study
      was to assess the effect of exercise training on the TNFalpha system and to
      evaluate the relationship with changes in insulin sensitivity. DESIGN AND
      METHODS: Sixteen obese women (body mass index (BMI)>27.8 kg/m(2)), 8 with normal
      (NGT) and 8 with impaired glucose tolerance (IGT), participated in an exercise
      training program which lasted for 12 weeks and included exercise performed on a
      bicycle ergometer at an individual intensity of 70% maximal heart rate, for 30
      min, 5 days a week. Anthropometrical measurements and blood biochemical analyses
      were performed, and plasma TNFalpha, sTNFR1 and sTNFR2 levels were assessed.
      Insulin sensitivity was evaluated using the hyperinsulinemic euglycemic clamp
      technique (insulin infusion: 50 mU x kg(-1)xh(-1)). RESULTS: At baseline, despite
      similar anthropometrical parameters, IGT subjects were markedly more insulin
      resistant and had higher TNFalpha and sTNFR2 concentrations. Exercise training
      increased insulin sensitivity and decreased TNFalpha and sTNFR2 levels, while
      sTNFR1 remained unchanged. The decrease in sTNFR2 was significantly related to
      the increase in insulin sensitivity; that relationship remained significant after
      adjustment for the concurrent changes in BMI, waist circumference, percentage of
      body fat, plasma glucose, insulin and free fatty acids. CONCLUSIONS: Regular
      physical exercise decreases TNFalpha system activity and that decrease may be
      responsible for the concurrent increase in insulin sensitivity.

PMID- 11517008
TI  - Insulin sensitivity in women: a comparison among values derived from intravenous
      glucose tolerance tests with different sampling frequency, oral glucose tolerance
      test or fasting.
AB  - OBJECTIVE: To determine the correlation between insulin sensitivity (S(I))
      obtained by the minimal model method applied to a frequently sampled (n=33)
      intravenous glucose tolerance test (FSIGT(33)), and values obtained by reduced
      FSIGTs, oral glucose tolerance test (OGTT), or fasting. DESIGN: Retrospective
      analysis on tests performed in prospective studies. METHODS: A total of 78
      FSIGT(33), and 59 OGTT were performed in non-diabetic women of which 10 were
      young cyclic females in the early follicular menstrual phase, 10 were young non
      obese subjects with polycystic ovary syndrome (PCOS) and 30 were in post
      menopause. Some of these individuals were investigated both prior to and during
      specified treatments. FSIGT(33) was transformed into FSIGT(22) and FSIGT(12) by
      removing samples from the analysis. Values of SI derived from reduced FSIGTs or
      calculations performed on glucose and insulin values observed in fasting
      conditions and/or during OGTT were related to those of FSIGT(33). RESULTS: S(I)
      values derived from FSIGT(33) were highly correlated with those derived from
      FSIGT(22) (r=0.965) or FSIGT(12) (r=0.955), but were only weakly correlated with
      those derived from fasting or OGTT calculations (r below 0.5). Between-group
      (PCOS vs normal) or within-group (prior to and during treatment) comparisons
      showed that reduced FSIGTs were only slightly less powerful than FSIGT(33) in
      detecting differences in S(I). CONCLUSIONS: In non-diabetic women, reduced FSIGTs
      but not calculations based on fasting or OGTT values may be used in place of
      FSIGT(33) to document S(I) and its variation.

PMID- 11517009
TI  - Circulating leptin concentrations and ovarian function in polycystic ovary
      syndrome.
AB  - OBJECTIVE: Polycystic ovary syndrome (PCOS) is characterized by ovarian
      dysfunction. Although the role of leptin in the control of reproduction is
      unclear, it may be involved in the control of ovulation. The aim of this cross
      sectional study was to determine the relationship between circulating leptin
      concentrations, and anthropometric, metabolic and endocrine variables as well as
      to examine a possible role of leptin in ovarian dysfunction associated with PCOS.
      DESIGN: Prospective observational study. METHODS: Seventy-one subjects with PCOS
      and 23 body mass index (BMI)-matched control subjects were recruited from
      infertility clinics. The association between serum leptin concentrations and the
      above variables was measured outwith the luteal phase. A subgroup of 24 PCOS
      subjects underwent more frequent blood sampling to monitor follicular growth and
      ovulation. The association between variables was measured by univariate,
      multivariate and partial correlation analyses. RESULTS: Serum leptin
      concentrations were not different in subjects with PCOS and controls, and were
      strongly associated with BMI in both groups. Twelve patients ovulated during the
      study period. There was no significant difference in serum leptin concentrations
      between ovulatory and anovulatory subjects. The relationship between BMI and
      leptin was similar in both groups. CONCLUSION: The results indicated that
      circulating leptin concentrations relate principally to total body fat in
      subjects with PCOS and controls, and that this is not associated with the
      facility for follicular development and ovulation in these patients.

PMID- 11517010
TI  - Leptin response to endogenous acute stress is independent of pituitary function.
AB  - There are close interactions between the adipocyte-derived hormone, leptin, and
      the anterior pituitary, especially the hypothalamic-pituitary-adrenal (HPA) axis.
      We investigated the relationship between the sympathetic adrenergic system and
      serum leptin levels, dependent on the function of anterior pituitary hormone
      axes, in 27 patients without a history of a hormone-secreting pituitary adenoma
      or other underlying endocrine disease. Based on responses in a routine insulin
      hypoglycemia test (ITT), the patients were classified as hypopituitary (HP;
      n=15), growth hormone deficient (GHD; n=6) or controls (CTR; 6 patients with
      normal responses). Nadir plasma glucose was 1.5+/-0.1 mmol/l at the time of
      maximum hypoglycemia. Each group had a significant increase in plasma
      epinephrine; however the magnitude of change was significantly higher in GHD
      (6.066+/-1.633 nmol/l) compared with HP patients (1.781+/-0.492 nmol/l) (P<0.01).
      The rise in norepinephrine was delayed (60 min) in the HP and CTR groups.
      However, in GHD patients there was a considerable increase at the time of
      hypoglycemia which was significantly different from HP (P<0.001) and CTR (P<0.05)
      patients. The increase in catecholamines was followed by a quick and significant
      decrease in serum leptin levels 45 min after an i.v. bolus injection of insulin
      in HP patients (-4.7+/-2.5%, P<0.05), which was significantly sustained after 60
      min (-5.6+/-2.5%, P<0.05). In CTR patients there was a significant decrease in
      serum leptin levels 60 min after i.v. insulin (-14.4+/-6.9%, P<0.05), while no
      significant response was observed in the GHD group, although 5 of 6 patients had
      decreased levels at 45 and 60 min. No differences between the groups were found
      by ANOVA. In conclusion, an acute increase in endogenous circulating
      catecholamines is associated with a quick decrease in serum leptin levels. Intact
      anterior pituitary function seems not to be essential for this hitherto poorly
      understood mechanism.

PMID- 11517011
TI  - Fibroblast growth factor receptor 1 (FGFR1) is over-expressed in benign prostatic
      hyperplasia whereas FGFR2-IIIc and FGFR3 are not.
AB  - OBJECTIVE: Benign prostatic hyperplasia (BPH) is one of the major public health
      problems among men: 50% of men over 55 are concerned with this disease. Prostate
      growth is under the control of androgens which act by means of several growth
      factors such as fibroblast growth factors (FGFs), epidermal growth factor and
      transforming growth factor beta. Basic FGF (bFGF) has been shown to stimulate
      prostatic stromal growth. In BPH, bFGF concentration is two- to threefold higher
      than in normal prostate. In this work, the bFGF receptors (FGFR1, FGFR2-IIIc and
      FGFR3) genes expression was evaluated to study the correlation between the
      expression of bFGF receptors and induction of BPH. METHODS: The expression of
      FGFRs was analyzed by RT-PCR, FGFR1 was localized by immunohistochemistry and
      protein expression was evaluated by Western blot. RESULTS: A two- to eightfold
      over-expression of FGFR1 was observed in BPH compared with normal prostates.
      FGFR1 was localized in the stroma both in BPH and in normal prostates and 1.5- to
      2.5-fold over-expression of the protein was observed. The expression of FGFR2
      IIIc and FGFR3, more secondary receptors, was not significantly different between
      BPH and normal prostates. CONCLUSIONS: bFGF receptors and particularly FGFR1 seem
      to be involved in the induction and evolution of BPH and probably potentiate bFGF
      over-expression effects in BPH.

PMID- 11517012
TI  - Hypoglycaemia due to insulin autoimmune syndrome: report of two cases with
      characterisation of HLA alleles and insulin autoantibodies.
AB  - OBJECTIVE: Insulin autoimmune syndrome (IAS) has been reported mainly in Japan
      and so far only 27 IAS cases have been described from outside Asia. We describe
      two unrelated Portuguese patients with IAS and characterise their insulin
      autoantibodies and HLA alleles. PATIENTS: Patient 1, a 24-year-old white female
      suffered an episode of unconsciousness in the late postprandial state and blood
      glucose was found to be 33 mg/dl with serum insulin levels of >3980 microIU/ml
      (normal range 0-30 microIU/ml). She was receiving monthly injections of
      penicillin G for the prophylaxis of recurrent tonsillitis. Patient 2, was a 19
      year-old white female, with episodes of sweating, hand tremor, weakness and
      hunger occurring in the postprandial state and blood glucose levels during the
      attacks of 28-56 mg/dl. Very high insulin levels (602-708 microIU/ml) were
      present. METHODS AND RESULTS: Anti-insulin antibodies, determined by a semi
      quantitative method, were strongly positive in both patients (91.7% in patient 1
      and 88.6% in patient 2; normal range < or =7%). Sephadex G-100 chromatography of
      the sera showed most of insulin immunoreactivity present in the void volume which
      was retained by an affinity column with anti-human-immunoglobulin G antibodies
      (87% and 95% from patients 1 and 2 respectively). Scatchard plot analysis and
      molecular typing of the DRB1 gene revealed a polyclonal antibody and DRB1*0406 in
      patient 1, and a monoclonal antibody and DRB1*0403 in patient 2. CONCLUSIONS:
      These two Portuguese patients with IAS had different HLA-DR4 subtypes and insulin
      autoantibodies: DRB1*0406 and a polyclonal antibody in a patient treated with
      penicillin, and DRB1*0403 and a monoclonal antibody in a patient with
      "idiopathic" IAS.

PMID- 11517013
TI  - Uncoupling protein 2 mRNA expression and respiratory parameters in Kupffer cells
      isolated from euthyroid and hyperthyroid rat livers.
AB  - OBJECTIVE: The levels of uncoupling protein 2 (UCP2) mRNA and determinants of
      respiration (ATP synthesis, proton leak and non-mitochondrial respiration) were
      evaluated in Kupffer cells isolated from the livers of normal euthyroid, acute
      hyperthyroid and chronic hyperthyroid rats. METHODS: After liver perfusion,
      Kupffer cells were purified by density-gradient centrifugation followed by
      counterflow centrifugal elutriation. UCP2 mRNA levels were measured by Northern
      blot and respiratory parameters by polarographic method. RESULTS: In cells
      isolated from hyperthyroid (tri-iodothyronine (T(3))-treated) rats, the effect of
      T(3) treatment on the UCP2 mRNA level varied: it was more than doubled (P<0.05)
      in acutely T(3)-treated rats but, after chronic (3-week) T(3) treatment, it was
      only 30% (not statistically significant) above the control (euthyroid) level. In
      Kupffer cells from the livers of chronic hyperthyroid rats, we observed an
      increase in total respiration rate, with an increase in the percentage
      attributable to the proton leak and a corresponding decrease in the percentage
      attributable to ATP synthesis (no alteration was observed in the percentage
      attributable to non-mitochondrial respiration). In the acute hyperthyroid rats,
      no significant differences were observed in any of the respiratory parameters,
      although they all tended to increase. CONCLUSION: These data are indicative of a
      possible uncoupling effect of UCP2 in Kupffer cells. T(3), by enhancing the
      expression of UCP2, could play a role in the energy homeostasis of these cells.

PMID- 11517014
TI  - Localization of glucocorticoid receptor interacting protein 1 in murine tissues
      using two novel polyclonal antibodies.
AB  - OBJECTIVE: Glucocorticoid receptor interacting protein 1 (GRIP1) is a coactivator
      that binds to the nuclear hormone receptors in a ligand-dependent manner and
      mediates transcriptional activation of the target genes. The aim of this study
      was to investigate GRIP1 expression in various murine tissues and whether the
      protein is nuclear, cytoplasmic, or both. DESIGN: Two novel polyclonal antibodies
      against amino acids 34-47 and 468-481 of GRIP1 were raised and characterized in
      order to study the GRIP1 expression with immunohistochemistry. RESULTS: Transient
      transfection studies with COS cells showed a clearly nuclear staining pattern and
      also immunohistochemical localization of GRIP1 was mainly nuclear, but
      cytoplasmic expression was seen as well. GRIP1 was expressed in epithelial cells
      of the submandibular gland, gastrointestinal tract, pancreas, kidney, uterus,
      mammary gland, testis, prostate, trachea, lungs and adrenal gland. GRIP1 was also
      detected in stromal cells of colon, rectum, urinary bladder, vagina, uterus,
      mammary gland and trachea, and to a lesser extent in esophagus, ureter, urethra,
      thymus and spleen. Smooth muscle cells of the gastrointestinal and urinary tract,
      uterus, epididymis, prostrate and bronchioles expressed GRIP1. Blood vessels of
      many organs, capsule of the kidney and prostate, mesovarium, adipocytes of the
      mammary gland, pericardium and cartilage of the trachea were also GRIP1-positive.
      Liver, thyroid gland and striated muscle did not express GRIP1. CONCLUSIONS:
      GRIP1 was expressed in a wide variety of murine organs, and expression varied
      between cell types and organs. In addition to mainly nuclear localization of
      endogenous GRIP1, cytoplasmic expression was seen as well.

PMID- 11517015
TI  - Discerning malignancy in adrenocortical tumors: are molecular markers useful?
AB  - OBJECTIVE: Adrenocortical carcinoma (ACC) is a rare neoplasm with poor prognosis.
      Discerning ACCs from benign adenomas histologically may be difficult if invasion
      into surrounding tissues or metastases are missing. DESIGN: In order to establish
      molecular markers for malignancy, we analyzed seven normal adrenals, three
      massive macronodular ACTH-independent adrenocortical hyperplasias (MMAHs), 30
      adrenocortical adenomas (ACAs) and ten ACCs. METHODS: All tissues were studied
      for the presence of alterations in the p53 tumor suppressor gene using the PAb
      1801 antibody, which detects mutant p53 protein and the pYNZ22 microsatellite
      marker to show loss of heterozygosity (LOH) at 17p, for expression of the
      proliferation-associated antigen Ki67 using the MIB1 antibody, for the rate of
      apoptotic tumor cells with the TdT-mediated dUTP biotin nick end labeling (TUNEL)
      method, and for LOH of 11q13 (menin gene locus) with the D11S956 microsatellite
      marker. RESULTS: 0/3 MMAH, 1/28 ACA and 3/10 ACC revealed immunopositive staining
      for p53. LOH for pYNZ22 was observed in 1/3 MMAH, 1/23 informative ACA and 6/6
      informative ACC. The rate of apoptotic cells was significantly higher in ACC
      (P<0.0001 by ANOVA) than in ACA but there was some overlap between groups. The
      Ki67 index (% immunopositive cells) was 1.9+/-1.30% (mean+/-s.d.) in normal
      adrenals, 3.47+/-1.37% in MMAH, and 2.11+/-1.01% in ACA. ACC had the highest Ki67
      index of 11.94+/-7.58% distinguishing all ACC from the ACA and MMAH studied with
      a cut-off level of 5%. LOH for 11q13 was detected in 2/3 MMAH, 5/26 ACA and 6/8
      ACC. CONCLUSIONS: We conclude that a Ki67 index above 5% is a sensitive and
      specific indicator of ACC and may be useful in the differentiation of adenomas
      from carcinomas.

PMID- 11517016
TI  - Effect of insulin on nitric oxide synthase-like immunostaining of arteries in
      various organs in Zucker diabetic fatty rats.
AB  - OBJECTIVE: Recently we reported that insulin treatment improved hypertension by
      inducing nitric oxide synthase (NOS) in Zucker diabetic fatty (ZDF) rats. In the
      present study, we investigated subtypes of NOS induced by insulin in arteries in
      various organs of ZDF rats using immunohistochemistry. DESIGN: Following
      treatment with insulin, localization of two subtypes of NOS in the arterial
      tissues of various organs was identified. METHODS: Following 4 weeks of s.c.
      injection of insulin, the aorta, cerebral cortex, pancreas and kidney were
      stained with polyclonal anti-endothelial NOS (eNOS) or anti-inducible NOS (iNOS)
      antibodies. RESULTS: In the aortic tissue, eNOS-like immunostaining was observed
      equally in the insulin-treated group and the control group, whereas iNOS-like
      immunostaining was present more densely in the insulin-treated group. In the
      cerebral artery, eNOS-like immunostaining was observed in the endothelium and was
      enhanced in the insulin-treated group. In the control group, iNOS-like
      immunostaining was absent in the cerebral artery, whereas immunostaining was
      densely observed in the insulin-treated group. In the interlobular artery of the
      pancreas, both eNOS-like and iNOS-like immunostaining was present in the control
      group and was enhanced in the insulin-treated group. In kidney, both eNOS-like
      and iNOS-like immunostaining was more densely present in the arterial tissue of
      the insulin-treated group. CONCLUSIONS: These results taken together suggest that
      insulin treatment induced NOS in arteries in various organs and that iNOS was
      more strongly induced than eNOS by insulin treatment in the ZDF rat.

PMID- 11517018
TI  - Effects of corticotropin-releasing hormone on locus coeruleus neurons in vivo: a
      microdialysis study using a novel bilateral approach.
AB  - OBJECTIVE: Stress-induced release of noradrenaline (NA) from locus coeruleus (LC)
      neurons is mainly regulated by corticotropin-releasing hormone (CRH). Tyrosine is
      a precursor of NA and plays an intriguing role in the regulation of NA release.
      DESIGN: We studied the effects of injecting CRH into the LC using a novel
      bilateral approach which relies on the mainly ipsilateral projections of LC
      neurons allowing stimulation of one hemisphere while using the other as control.
      To analyze the modification of the CRH effect, tyrosine was given
      intraperitoneally. A combination of CRH and its antagonist d-Phe was administered
      for validation of the specificity of CRH effects. METHODS: Wistar rats were used
      in all experiments. Injections were made through fused silica capillaries
      implanted into both LCs and microdialysis samples were collected bilaterally from
      the prefrontal cortex (PFM) every 20 min for 1 h before and 3 h after injections.
      The effects of LC stimulation were investigated by determining 3-methoxy-4
      hydroxyphenylglycol (MHPG) in the dialysates. RESULTS: Following CRH injection
      into one LC and contralateral infusion of artificial cerebrospinal fluid (aCSF),
      MHPG levels, which are indicative of NA release, increased only in the
      ipsilateral PFM. These effects were blocked by d-Phe. Simultaneous administration
      of tyrosine i.p. led to a significant prolongation of MHPG release. CONCLUSIONS:
      These data provide the first physiological evidence of unilateral LC projections
      with the bilateral stimulation design proving to be a very valuable tool for the
      study of LC firing rate, to decrease number of animals and time expenditure.
      Prolongation of MHPG release after tyrosine supplementation is most likely due to
      increased NA synthesis.

PMID- 11517017
TI  - 1-alpha,25-Dihydroxyvitamin D3 (1,25(OH)(2)D(3)) hampers the maturation of fully
      active immature dendritic cells from monocytes.
AB  - OBJECTIVE: To study the effects of the active metabolite of vitamin D(3),
      1,25(OH)(2)D(3), an immunomodulatory hormone, on the generation of so-called
      immature dendritic cells (iDCs) generated from monocytes (Mo-iDCs). DESIGN AND
      METHODS: Human peripheral blood monocytes were cultured to iDCs in the presence
      of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)
      4 for 1 week, with or without the extra addition of 10(-8) M 1,25(OH)(2)D(3) to
      the culture. Their phenotypes (CD14, CD1a, CD83, HLA-DR, CD80, CD86 and CD40
      expression) were examined by fluorescence-activated cell sorting, and their T
      cell stimulatory potential was investigated in allogeneic mixed lymphocyte
      reaction (allo-MLR). Additionally, their in vitro production of IL-10, IL-12 and
      transforming growth factor beta (TGF-beta) were examined by using the enzyme
      linked immunosorbent assay. RESULTS: When 1,25(OH)(2)D(3) was added to monocytes
      in culture with GM-CSF and IL-4, it hampered the maturation of Mo-iDCs. First,
      the phenotype of the 1,25(OH)(2)D(3)-differentiated DCs was affected, there being
      impaired downregulation of the monocytic marker CD14 and impaired upregulation of
      the markers CD1a, CD83, HLA-DR, CD80 and CD40. CD86 was expressed on more
      1,25(OH)(2)D(3)-differentiated DCs. Secondly, the T-cell stimulatory capability
      of 1,25(OH)(2)D(3)-differentiated DCs was upregulated relative to the original
      monocytes to a lesser degree than DCs differentiated without 1,25(OH)(2)D(3) when
      tested in an allo-MLR. With regard to the production of cytokines, Staphylococcus
      aureus cowan 1 strain (SAC)-induced IL-10 production, although not enhanced,
      remained high in 1,25(OH)(2)D(3)-differentiated DCs, but was strongly
      downregulated in DCs generated in the absence of 1,25(OH)(2)D(3). SAC/interferon
      gamma-induced IL-12 production was clearly upregulated in both types of DC
      relative to those of the original monocytes, and TGF-beta production was
      downregulated. CONCLUSION: Our data confirm earlier reports showing that
      1,25(OH)(2)D(3) hampers the maturation of fully active immunostimulatory major
      histocompatibility complex (MHC) class II+, CD1a+, CD80+ DCs from monocytes. Our
      data supplement the data from other reports by showing that the expression of
      CD86 was upregulated in 1,25(OH)(2)D(3)-differentiated DCs, whilst the capacity
      for IL-10 production remained high. Collectively, these data are in line with
      earlier descriptions of suppressive activities of this steroid-like hormone with
      respect to the stimulation of cell-mediated immunity.

PMID- 11517019
TI  - Aerosols and devices.
AB  - The success of aerosol therapy depends upon the delivery of ample amounts of the
      drug to appropriate sites in the lung with minimal side effects. Successful
      aerosol therapy delivery systems must provide sufficient respirable particles or
      droplets, with minimal loss of the drug. Ultimately, the patient must be able to
      use the device easily, maintain it, and derive clinical benefit from the drug
      delivered from the system.

PMID- 11517020
TI  - Aerosol therapy for children.
AB  - Pediatric aerosol therapy encompasses a range of patients from premature neonates
      with birth weights as low as 500 grams to adult size teenagers. This article
      focuses on the care of smaller infants and children in whom anatomic differences
      present substantial challenges for aerosol delivery.

PMID- 11517021
TI  - Aerosol and inhaled therapy in treatment of acute adult airway obstruction in the
      emergency department.
AB  - This article reviews the aerosol therapy and inhalotherapy in the nonintubated
      adult patient with acute severe asthma in the emergency department. Factors
      influencing lower respiratory deposition of aerosols are summarized. The use of
      inhaled beta2-adrenergic agonists, anticholinergic drugs, corticosteroids, and
      heliox are discussed.

PMID- 11517022
TI  - Inhalation therapy during mechanical ventilation.
AB  - An increasing number of pharmacologic agents, including bronchodilators,
      prostaglandin, proteins, surfactant, mucolytics, and antibiotics are administered
      to mechanically ventilated patients by the inhalation route. To achieve a
      therapeutic effect, adequate amounts of an inhaled agent must be delivered to the
      desired site of action. The delivery of inhaled drugs to the lower respiratory
      tract of mechanically ventilated patients is complicated by deposition of the
      aerosol particles in the ventilator circuit and endotracheal tube, and the
      factors governing pulmonary deposition in mechanically ventilated patients are
      different from those in ambulatory patients. Meticulous adherence to several
      steps in the technique of aerosol administration is necessary for successful
      aerosol therapy in mechanically ventilated patients. With a proper technique of
      administration, an increasing number of inhaled drugs may be administered safely,
      conveniently, and effectively to mechanically ventilated patients.

PMID- 11517023
TI  - Aerosols for systemic delivery of macromolecules.
AB  - During the past 50 years, aerosol therapy with small molecules has become the
      mainstay for managing lung diseases such as asthma, chronic obstructive pulmonary
      disease, and cystic fibrosis. During the past decade, a new therapeutic paradigm
      has evolved-the delivery of macromolecules into the systemic circulation through
      the lung. Systemic pulmonary therapy with proteins and peptides resulted from
      major developments in dry powder drug formulations and aerosol delivery
      technology. These new technologies will enable the treatment of systemic disease,
      such as diabetes mellitus, noninvasively by means of the deep lung. Within a
      decade, it is likely that many medications will be administered in this way.

PMID- 11517024
TI  - Promoting adherence to inhaled therapy: building partnerships through patient
      education.
AB  - Optimal treatment outcomes are dependent upon patient adherence to therapy.
      Problems in adherence can be overcome by developing a professional-patient
      partnership that has the goal of developing communication between the partners,
      mutual accountability, respect for personal values and viewpoints, and shared
      decision making. The process of patient education is shaped by the needs of this
      developing partnership rather than a-priori goals established by the
      professional.

PMID- 11517025
TI  - Laboratory evaluation of metered-dose inhalers with models that simulate
      interaction with the patient.
AB  - Laboratory evaluation of aerosol generating-devices is usually performed under
      conditions of constant airflow. The performance of aerosol-generating devices
      with different tidal volumes and inspiratory airflows encountered in clinical
      practice cannot be determined by these methods. To overcome this problem, models
      have been developed that simulate patients' breathing pattern, provide
      measurements of inhaled or respirable mass, and the proportion of aerosol
      exhaled. This article explores the development of such a model.

PMID- 11517026
TI  - Future directions in aerosol therapy.
AB  - An unprecedented growth in new technology and clinical applications of aerosol
      therapy is forecast for the new millennium. The most promising areas of
      investigation in the aerosol field relate to improvements in the pulmonary
      deposition of aerosol, improved synchronization between the patient's breathing
      and aerosol generation, targeting of aerosol to specific sites in the lung,
      improvements in the formulations of inhaled drugs, modulated release of inhaled
      drugs, and use of inhaled drugs for systemic therapy. Moreover, gene therapy by
      the inhaled route offers the prospects of a cure for a variety of pulmonary
      disorders. Future developments in the aerosol field are expected to radically
      change the management of patients across several medical specialties.

PMID- 11517027
TI  - Principles and history of closed-loop controlled ventilation.
AB  - Respiratory management of intubated patients is a complex problem, even if airway
      management, sedation, and infection control are excluded and only the limited
      problem of "how to set a ventilator" is considered. Four dimensions shape the
      overall strategy for setting a ventilator: time, physiologic task, primary lung
      disease, and general therapeutic approach. Initiation (start-up), maintenance,
      and weaning are the principal dimensions in time. This article discusses the
      closed-loop control method.

PMID- 11517028
TI  - Fuzzy logic and mechanical ventilation.
AB  - Closed-loop control can achieve appropriate ventilation of the lungs in a healthy
      person by involving the continuous interaction of three components: sensors,
      controllers, and effectors. The sensors are the chemo-mechanoreceptors, which
      continuously monitor key bodily functions affected by ventilation. This
      information is relayed to the controllers, the respiratory centers in the brain,
      allowing them to determine how actual ventilation compares with that needed by
      the body. Finally, the controllers direct the effectors, the muscles of
      respiration, to adjust the ventilation accordingly. When a patient is in
      respiratory failure, the effector's role is taken over by a mechanical
      ventilator. The issue that is considered in this article is how the physician
      might be taken out of the feedback loop.

PMID- 11517029
TI  - Knowledge-based systems for automatic ventilatory management.
AB  - In intensive care and anesthesia, the demand for computerized medical assistants
      is potentially considerable, to filter and synthesize the growing mass of
      clinical parameters and information available. The authors detail how knowledge
      based computerized assistants can be constructed for automatic ventilation
      management and report clinical results obtained with such a system for closed
      loop control of pressure support ventilation and decision for extubation.

PMID- 11517030
TI  - Dual control modes: combining volume and pressure breaths.
AB  - New modes of ventilator operation are often introduced without rhyme or reason.
      The dual control modes are, however, a response of the manufacturers to clinician
      desire to provide constant minute volume/tidal volume while operating in the
      pressure support or pressure control mode. Dual control modes allow the
      ventilator to control pressure or volume. The ventilator cannot control pressure
      and volume at the same time, so it is an either/or phenomenon. Dual control modes
      can operate "within a breath" or on a "breath to breath" basis. Dual control
      within a breath refers to a technique whereby the ventilator switches from
      pressure to volume control in the middle of a breath. In the technique of dual
      control breath to breath, all breaths are pressure control breaths, but the level
      of pressure varies from breath to breath in an effort to maintain a constant
      tidal volume.

PMID- 11517031
TI  - Adaptive lung ventilation.
AB  - Adaptive lung ventilation (ALV) is a method of closed-loop mechanical ventilation
      analogous to modern closed-loop technology in aviation such as the autopilot and
      automatic landing system. The algorithm of the controller of ALV is designed to
      automatically provide pressure-controlled synchronized intermittent mandatory
      ventilation (P-SIMV) and weaning as individually required in any clinical
      situation. The synchronized pressure limited breaths constantly adapt to the
      patient requirements to encourage optimal alveolar ventilation with minimal
      adverse physiological disturbance and timely weaning. The ease of application,
      efficiency, and safety of the first ALV controllers have been demonstrated in
      lung models, in patients with normal lungs undergoing general anesthesia, in
      patients requiring unusual positioning, in transition to and from one-lung
      anesthesia, and in long-term ventilation of patients with various lung
      pathologies and in weaning patients who have restrictive or obstructive pulmonary
      disease. Prospective comparative studies of ALV versus other currently used
      manually selected modes of mechanical ventilation, such as the one reported in
      this article, should confirm the safety and identify the benefits of this form of
      advanced closed-loop mechanical ventilation technology.

PMID- 11517032
TI  - Adaptive support ventilation.
AB  - Adaptive support ventilation (ASV) is a newer form of closed-loop ventilation
      control available on the Galileo ventilator (Hamilton Medical). ASV provides
      automated selection of initial ventilator parameters based on measurements of
      patient lung mechanics and breathing effort. After initiation, ASV will "titrate"
      ventilator output (mandatory breath rate, tidal volume, inspiratory pressure,
      inspiratory time, and I to E ratio) to maintain a calculated optimal breathing
      pattern that ensures delivery of a clinician selected minute ventilation target.
      ASV may be thought of as an "electronic" ventilator management protocol that may
      improve the safety and efficacy of mechanical ventilation. Additional clinical
      investigations regarding the effect of ASV on outcome, ventilator days, and so
      forth are forthcoming.

PMID- 11517033
TI  - Closed-loop support of ventilatory workload: the P0.1 controller.
AB  - Conventional mechanical ventilation modes fail to provide a setting for direct
      control of a patient's ventilatory effort; however, with all modes clinicians may
      manipulate conventional controls to modulate the spontaneous respiratory activity
      of the patient. For instance, during pressure support ventilation the spontaneous
      respiratory activity can be decreased by increasing the pressure support level to
      achieve an adequate residual load for the respiratory muscles of the patient,
      neither too high nor too low. This choice is based on the clinical observation. A
      closed-loop controller can be envisaged to accomplish automatically, precisely,
      and on a breath-by-breath basis, this difficult task. The closed-loop controller
      should be based on the continuous and possibly noninvasive monitoring of a
      parameter that quantitatively reflects the patient's effort for ventilation.
      Occlusion pressure at 0.1 second (P0.1) can be the ideal parameter for that
      purpose. The authors have designed a noninvasive method for breath-by-breath
      monitoring of P0.1, and then a closed-loop control mode that automatically adapts
      the pressure support level to reach and maintain a user-set P0.1 and alveolar
      volume. This article discusses features and performance of this P0.1 control
      mode, fields of application, known limits, and possible future improvements.

PMID- 11517034
TI  - Proportional assist ventilation.
AB  - Partial ventilatory support techniques are intended for patients who are unable
      to maintain a normal alveolar ventilation, despite normal central control for
      respiration. Proportional assist ventilation (PAV) is a novel mode of partial
      ventilatory support in which the ventilator generates an instantaneous
      inspiratory pressure in proportion to the instantaneous effort of the patient. In
      theory, PAV should normalize the neuro-ventilatory coupling by making the
      ventilator an extension of patient's respiratory muscles, while leaving to the
      patient the entire control of all aspects of breathing. PAV, however, shares a
      common problem with the conventional partial ventilatory support modes. In
      mechanically ventilated patients, the respiratory system impedance may change
      over time. These changes may impair the good matching between ventilator output
      and patient's ventilatory demand and lead to patient-ventilator asynchrony. To
      take full advantage of PAV, the authors believe that PAV should continuously and
      automatically adapt to the respiratory system passive mechanics, assessed by
      continuous noninvasive measurement of total elastance and resistance.

PMID- 11517035
TI  - Automatic tube compensation.
AB  - In this article automatic tube compensation (ATC) is described with respect to
      working principle, to technical realization, and to clinical experience. ATC,
      based on an indirect closed-loop working principle, compensates for the flow
      dependent pressure drop across the tracheal tube during both inspiration and
      expiration. ATC reduces patient work of breathing, increases respiratory comfort,
      and allows prediction of successful extubation. ATC is not a stand-alone
      ventilatory mode, but rather a component of flow-proportional pressure support
      that can be combined with all conventional ventilatory modes.

PMID- 11517036
TI  - Automation of expiratory trigger sensitivity in pressure support ventilation.
AB  - Patients under pressure support ventilation sometimes encounter patient
      ventilator asynchrony in the transition from inspiration to expiration, that is,
      expiratory asynchrony. This problem is caused by the incompatibility of the fixed
      level of expiratory trigger sensitivity termination criteria (i.e., flow
      termination criteria) in the ICU ventilators to various patient conditions. The
      user-adjustable expiratory trigger sensitivity implemented in some newly released
      ventilators has been experienced to be difficult to use and unable to adapt ever
      changing patient conditions without user intervention, although it provides more
      flexibility. This article elucidates the rationale for automatic control of the
      expiratory trigger sensitivity and evaluates the automation system with a bench
      setup. The evaluation data suggest that good expiratory synchronies can be
      achieved through automatic adjustments of expiratory trigger sensitivity.

PMID- 11517037
TI  - PACS: radiology in the digital world.

PMID- 11517038
TI  - High-resolution CT of the lungs.

PMID- 11517040
TI  - Is diagnostic review of radiotherapy-planning CT scans important in the conformal
      therapy era?
AB  - OBJECTIVE: Detailed CT scans are often acquired during the radiotherapy planning
      process. This study was performed to determine the incidence of important benign
      and cancer-related CT findings on these scans. SUBJECTS AND METHODS: From
      December 1998 to December 2000, 162 radiotherapy patients who were to be treated
      curatively underwent treatment planning CT scans on a helical scanner in the
      radiology department at Washington Hospital, Fremont, CA. All CT scans were
      prospectively interpreted relative to diagnoses, and reports were dictated for
      the medical records. The diagnostic reports and records on all patients were
      reviewed to determine the incidence of previously unknown benign or cancer
      related findings, the impacts of such findings on treatment, and the need for
      additional radiologic studies or procedures on the basis of the CT
      interpretations. RESULTS: Incidental benign findings were noted for 32 patients
      (20%). Potentially important benign findings were noted for three patients: two
      with aneurysms and one with a possible deep vein thrombosis. Potentially cancer
      related findings were reported in 20 patients: a single liver lesion (four
      patients), multiple liver lesions (two patients), possible or probable
      lymphadenopathy (11 patients), abnormal soft tissue (one patient), a small-bowel
      obstruction (one patient), and a breast mass (one patient). After reviewing prior
      diagnostic studies and obtaining additional recommended studies, the physicians
      found that only three of the previously unknown findings required further
      investigation: two aneurysms, which did not require near-term treatment, and one
      metastatic neck node. CONCLUSION: Routine diagnostic interpretation of
      radiotherapy planning scans resulted in few important medical findings and
      changed patient care for less than 1% of the patients.

PMID- 11517041
TI  - Reliability of soft-copy versus hard-copy interpretation of emergency department
      radiographs: a prototype study.
AB  - OBJECTIVE: The purpose of this study was to compare the diagnostic reliability of
      hard-copy and soft-copy interpretation of radiographs obtained in the emergency
      department using a methodology for evaluating imaging systems when independent
      proof of the diagnosis is not available. MATERIALS AND METHODS: We collected
      radiographs from a stratified sample of 100 patients seen in the emergency
      department. The images were obtained using computed radiography, and the digital
      images were printed on film and stored for display on a workstation. A group of
      seven experienced radiologists reported the cases using both film and the
      workstation display. The results were analyzed using mixture distribution
      analysis (MDA). RESULTS: The reliability expressed as the percentage of agreement
      of a typical observer relative to the majority was computed from the MDA. The
      result was 90% for both hard copy and soft copy with bootstrap confidence
      intervals of 86-94%. CONCLUSION: We conclude that, in the emergency department,
      soft-copy interpretation is as reliable as hard-copy interpretation. The strength
      of this conclusion depends on the validity of the MDA approach as well as the
      extent to which the observer sample and case sample are representative of the
      emergency department.

PMID- 11517042
TI  - The good samaritan.

PMID- 11517043
TI  - Reassessment of breast cancers missed during routine screening mammography: a
      community-based study.
AB  - OBJECTIVE: The purpose of this study was to have a series of screening mammograms
      from routine practice, including false-negative results, reviewed by peer
      community-based experienced radiologists to determine the percentage of these
      false-negative findings that might be considered detectable. MATERIALS AND
      METHODS: All screening cases for 1997 and 1998 were identified from the Carolina
      Mammography Registry. Mammographic assessments from community mammography
      practices were linked with population-based cancer outcomes. The findings of four
      community-based radiologists who reviewed the mammograms of 339 asymptomatic
      women were 93 false-negatives, 180 true-negatives, and 66 false-positives. The
      percentage of false-negative, true-negative and false-positive findings on breast
      films that reviewers evaluated was determined. The findings of the reviewers were
      compared with the original interpreting radiologists' assessments. RESULTS: The
      overall breast-specific workup rate by the reviewing radiologists was 21%. The
      average workup rate for the false-negative findings was 42% (range, 35-51%).
      Adjusting for the 13% workup rate in the cancer-free breasts, the percentage of
      false-negative findings that were detectable was estimated to be 29%. CONCLUSION:
      This peer review of screening mammograms from a population-based screening
      registry estimated a missed detectable cancer rate of 29%. Thus, 71% of cancers
      missed at screening would not have been worked up by peers in the same community.

PMID- 11517044
TI  - Association of recall rates with sensitivity and positive predictive values of
      screening mammography.
AB  - OBJECTIVE: The performance of screening mammography is measured mainly by its
      sensitivity, positive predictive value, and cancer detection rate. Recall rates
      are also suggested as a surrogate measure. The main objective of this study was
      to measure the effect on sensitivity and positive predictive value as recall
      rates increase in the community practice of mammography. MATERIALS AND METHODS:
      Mammography and pathology data are linked in the Carolina Mammography Registry, a
      population-based registry of screening mammography. Our mammography database is
      created from prospectively collected data from mammography facilities; the data
      include information on the woman and the imaging studies. Our pathology database
      is created from prospectively collected breast pathology data received from
      pathology sites and the Central Cancer Registry. Women in the registry who were
      40 years old and older and who underwent screening mammography between January
      1994 and June 1998 were included. "Recall rate" was defined as the percentage of
      screening studies for which further workup was recommended by the radiologist.
      RESULTS: The study included 215,665 screening mammograms. The mean age of the
      women was 56 years. The recall rates of the average practice ranged from 1.9% to
      13.4%. Sensitivity rose from a mean of 65% in the lowest recall rates to 80.2% at
      the highest level of recall rates. The positive predictive value of screening
      decreased from 7.2% in the lowest level of recall to 3.3% in the highest. As
      recall rates increased, sensitivity increased very little beyond a recall rate of
      4.8%, and positive predictive value began decreasing significantly at a recall
      rate of 5.9%. CONCLUSION: Practices with recall rates between 4.9% and 5.5%
      achieve the best trade-off of sensitivity and positive predictive value.

PMID- 11517046
TI  - Observer variability and applicability of BI-RADS terminology for breast MR
      imaging: invasive carcinomas as focal masses.
AB  - OBJECTIVE: The purpose of this study was to assess whether the descriptive
      terminology and final assessment categories of the Breast Imaging Reporting and
      Data System (BI-RADS) lexicon can be used for breast carcinomas detected on MR
      imaging and to assess the inter- and intraobserver variabilities in the use of
      the descriptors and final assessment categories. MATERIALS AND METHODS: In 82
      patients, 101 masses, including 68 infiltrating carcinomas and 33 benign lesions,
      were interpreted independently by four radiologists and described by BI-RADS
      terminology with respect to mass shape and margin and BI-RADS final assessment
      categories. The enhancement pattern of the mass was also reported. In addition,
      two radiologists interpreted each case twice to evaluate intraobserver
      variability. The final case set for analysis was the 68 infiltrating carcinomas.
      RESULTS: Most of the infiltrating carcinomas were described as irregular,
      spiculated, and heterogeneously enhancing masses. The final impression of the 68
      carcinomas was BI-RADS category 5 (highly suggestive of malignancy) in 41 (61%),
      category 4 (suspicious abnormality) in 24 (35%), and category 3 (probably benign)
      in three (4%). Enhancement pattern was heterogeneous in 40 (59%), homogeneous in
      14 (21%), and rim in 14 (21%). Interobserver agreement was moderate for mass
      margin, shape, enhancement, and final assessment category. CONCLUSION: This study
      suggests that the mammographic BI-RADS lexicon with some modifications may be
      applied to describe the features of infiltrating carcinoma seen on breast MR
      imaging.

PMID- 11517047
TI  - Percutaneous imaging-guided core breast biopsy: 5 years' experience in a
      community hospital.
AB  - OBJECTIVE: This study reports the results of a percutaneous imaging-guided core
      breast biopsy program in a community hospital. MATERIALS AND METHODS: We reviewed
      the prospectively collected results of our imaging-guided core biopsy program
      during its first 5 years (1994-1998). A total of 1333 lesions (94% of which were
      Breast Imaging Reporting and Data System (BI-RADS) assessment category 4) were
      sampled in 1183 patients. Patients with BI-RADS assessment category 5 lesions
      were referred to surgeons. Stereotactic guidance was used for the core biopsy of
      506 lesions, and sonography was used to guide the predominantly 16-gauge needle
      core biopsy of 827 solid masses. RESULTS: One hundred forty-seven cancers were
      diagnosed in 1333 biopsies, resulting in a positive yield of 11%. Of 1020
      patients with benign, concordant core biopsy results, 981 (96%) had at least one
      follow-up imaging examination within 36 months of the biopsy. Nineteen (2%) of
      these 1020 patients had a suspicious change at follow-up; 18 of these patients
      underwent surgical excision with benign findings. No cancers were found at
      imaging follow-up or by tumor registry linkage. All malignant core biopsy results
      were confirmed as malignant at surgical excision (positive predictive value
      100%). Twenty-two patients with atypical ductal hyperplasia at core biopsy had
      subsequent surgery, and 12 (55%) of them were found to have cancer at surgery.
      CONCLUSION: An imaging-guided core biopsy program, developed and implemented by a
      small group of radiologists in a community hospital, can achieve successful
      results and provide an important service to patients and a cost-effective
      alternative to surgical biopsy. Our program emphasized sonographic guidance and
      achieved high follow-up compliance.

PMID- 11517048
TI  - Bracketing wires for preoperative breast needle localization.
AB  - OBJECTIVE: The purpose of this study was to evaluate the outcomes of bracketing
      wire placement during preoperative breast needle localization. SUBJECTS AND
      METHODS: We prospectively examined mammograms of 1057 consecutive lesions that
      had preoperative needle localization and surgical excision and classified the
      lesions according to Breast Imaging Reporting and Data System (BI-RADS) final
      assessment categories. Bracketing wires, defined as multiple wires placed to
      delineate the boundaries of a single lesion, were used in 103 (9.7%) of 1057
      lesions. Medical records, imaging studies, and histologic findings in these 103
      lesions were reviewed. RESULTS: Of 103 bracketed lesions, median lesion size was
      3.5 cm (range, 1.5-9.5 cm). Ninety-three lesions (90.3%) contained
      calcifications; 65 lesions (63.1%) were BI-RADS category 5 (highly suggestive of
      malignancy); and 33 lesions (32.0%) were percutaneously proven cancers. The
      median number of wires placed was two (range, 2-5). Surgical histologic findings
      were carcinoma in 75 lesions (72.8%), atypical hyperplasia in eight lesions
      (7.8%), and benign in 20 lesions (19.4%). Of 42 calcific lesions that were
      bracketed and had postoperative mammograms available for review, complete removal
      of suspicious calcifications was accomplished in 34 (81.0%). Of 75 cancers that
      were bracketed, clear histologic margins of resection were obtained in 33
      (44.0%). CONCLUSION: Bracketing wires were used during preoperative needle
      localization primarily for larger calcific lesions that were proven cancers or
      were highly suggestive of malignancy (BI-RADS category 5). Bracketing wires may
      assist the surgeon in achieving complete excision of calcifications, but
      bracketing wires do not ensure clear histologic margins of resection.

PMID- 11517049
TI  - Stromal fibrosis of the breast.
AB  - OBJECTIVE: The purpose of this retrospective study was to describe the imaging
      features of stromal fibrosis of the breast and to determine the false-negative
      rate (number of cancers missed) at percutaneous biopsy. MATERIALS AND METHODS:
      Between January 1997 and October 1999, 1095 imaging-guided core biopsies were
      performed. Patients were included in our study if stromal fibrosis was the
      predominant histologic finding. Cores adjacent to previous excisional biopsies or
      from calcified lesions were excluded. RESULTS: Stromal fibrosis was diagnosed in
      74 (6.8%) of 1095 imaging-guided core needle biopsies in 73 patients. The 10
      mammographic lesions were variable in appearance. Most of the sonographic lesions
      were indeterminate, with 16 (25%) of 64 showing suspicious features. Discordant
      imaging resulted in three patients having a second core biopsy and nine patients
      having an excisional biopsy. The two false-negative findings were the result of
      an infiltrating lobular carcinoma and an infiltrating ductal carcinoma, the
      latter diagnosis delayed for 6 months. CONCLUSION: The low incidence (2.7%) of
      missed cancers in our series suggests that patients diagnosed at core biopsy as
      having stromal fibrosis can be treated conservatively with a short-term follow-up
      protocol. However, it would be prudent to continue to recommend either a second
      core biopsy or an excisional biopsy for imaging features that cannot be reliably
      differentiated from malignancy.

PMID- 11517050
TI  - Patient expectations and costs of immediate reporting of screening mammography:
      talk isn't cheap.
AB  - OBJECTIVE: Our purpose was to determine whether patients prefer immediate or
      delayed results of screening mammography and to determine the cost of immediate
      reporting at our institution. MATERIALS AND METHODS: A survey was anonymously and
      randomly distributed to 129 women who were 35-70 years old during a visit to
      their primary care physician, asking the women's preference for receiving
      mammography results by one of two systems: by letter with a return visit for any
      additional tests; or by speaking at once with the radiologist, with the option of
      additional tests being performed during the same visit. Patients' willingness to
      pay for the latter service was also determined. A cost identification model was
      constructed using commercially available software. We considered the impact on
      radiologists' and technologists' time and the need for additional equipment and
      space, and we analyzed the effect on the cost of immediate reporting. RESULTS:
      One hundred twenty (93%) surveys were completed. Eighty women (67%) preferred
      immediate reporting, and 62 (78%) of these 80 patients would wait 30-60 min. The
      additional cost of immediate reporting is $28.22 per patient. Only 11% of
      patients were willing to pay this additional cost. When new equipment and space
      were not required, the cost would increase by $4.38. This cost was most
      influenced by the time required to give patients normal results. CONCLUSION: Most
      surveyed patients preferred speaking with a radiologist immediately but were
      unwilling to pay additional fees. Radiologists, hospital administrators, and
      health care planners must be aware of the costs of immediate reporting and must
      factor these costs into any change in hospital or national policy.

PMID- 11517051
TI  - Stenting as first option for endovascular treatment of malignant superior vena
      cava syndrome.
AB  - OBJECTIVE: Endoprostheses were inserted in cancer patients with superior vena
      cava syndrome to assess their effectiveness as first-choice, initial treatment
      for relief of symptoms. SUBJECTS AND METHODS: Wallstent prostheses (n = 73) of
      various lengths (5-14 cm; median, 7 cm) and diameters (10-16 mm; median, 16 mm)
      were inserted in 52 cancer patients (51 men, 1 woman; age range, 44-78 years;
      mean, 63 years) who were diagnosed and confirmed by cavography or phlebography as
      having superior vena cava syndrome. A single stent was sufficient in 37 patients,
      two stents were required in 11, three stents in two, and four stents in another
      two patients. Contraindications for the procedure were severe cardiopathy or
      coagulopathy. RESULTS: Resolution of symptoms was achieved in all patients within
      72 hr. At follow-up, six obstructions, one partial migration to the right atrium,
      two incorrect placements, and four stent "shortenings" were noted. All were
      successfully resolved by repeated stenting. Symptom-free survival ranged from 2
      days to 17 months (mean, 6.4 months). At the time of this writing, eight patients
      are alive and have patent stents. The rest have died from their cancer.
      CONCLUSION: The Wallstent vascular endoprosthesis is an effective initial
      treatment in superior vena cava syndrome of neoplastic origin. Morbidity and
      complications are minimal. Clinical relief of symptoms is rapid; therefore, the
      Wallstent endoprosthesis is highly recommended as the first choice for palliative
      treatment of superior vena cava syndrome, especially because the clinical
      decision for subsequent chemotherapy or radiotherapy or surgery is not in any way
      prejudiced.

PMID- 11517052
TI  - Low-dose thrombin injection to treat iatrogenic femoral artery pseudoaneurysms.
AB  - OBJECTIVE: Treatment of iatrogenic femoral artery pseudoaneurysms with thrombin
      injection has been reported as an efficacious and safe procedure. The major risk
      of this procedure is distal limb ischemia from thrombosis, resulting from
      thrombin escape. The cumulative average dose of thrombin reported in the
      literature is approximately 1100 U per patient. Minimizing the thrombin dose may
      reduce the risks of the procedure. This study reports our experience with low
      dose thrombin injection for the treatment of pseudoaneurysms. MATERIALS AND
      METHODS: Twenty-three patients with 26 postcatheterization femoral
      pseudoaneurysms were administered thrombin injection with color-flow Doppler
      sonographic guidance. Pseudoaneurysm volume ranged from 1 to 41 cm(3) with an
      average of 6.7 cm(3) and a median of 4 cm(3). Two patients received therapeutic
      doses of IV heparin for anticoagulation. When possible, the neck of the
      pseudoaneurysm was occluded during the injection to promote stagnation and
      prevent thrombin leakage. Sonographic follow-up was routinely performed after 24
      hr. RESULTS: An average dose of 192 U of thrombin was used (range, 50-450 U), and
      time to coagulation ranged from 10 to 60 sec. All 26 pseudoaneurysms were
      successfully thrombosed, although one required repeated treatment because of
      recanalization noted at 1-day follow-up. There were no complications. CONCLUSION:
      Doses of thrombin at an average of fivefold lower than previously reported were
      effective in the treatment of 26 iatrogenic femoral pseudoaneurysms, even in the
      presence of anticoagulation. This experience shows that a much smaller dose of a
      potentially dangerous medication can achieve the same efficacy as previously used
      higher doses.

PMID- 11517053
TI  - Internal iliac artery embolization before endovascular repair of abdominal aortic
      aneurysms: frequency, efficacy, and clinical results.
AB  - OBJECTIVE: The aim of our study was to assess the frequency, efficacy, and
      incidence of adverse effects of internal iliac artery embolization. MATERIALS AND
      METHODS: Of 343 patients examined for stent-graft repair, 147 were suitable for
      endovascular treatment. Fifty-five patients underwent preprocedural embolization
      of the internal iliac artery either unilaterally (46 patients) or bilaterally
      (nine patients). Successful embolization was assessed angiographically and with
      helical CT follow-up examinations. Colonic ischemia was ruled out clinically or
      colonoscopically. Buttock claudication, and sexual dysfunction in men, were
      evaluated through a questionnaire. RESULTS: Embolization of the internal iliac
      artery increased by 16% the percentage of patients for whom endovascular repair
      was suitable. After successful embolization in all patients, routine CT follow-up
      examinations after a mean time of 16.7 months showed no evidence of endoleaks
      related to retrograde perfusion via embolized internal iliac arteries.
      Nevertheless, in all patients who had undergone embolization, a primary endoleak
      was detected in 43.4% at the first postoperative CT examination. None of our
      patients had evidence of colonic ischemia. Clinical follow-up data of 46 patients
      were available. Of these patients, mild to severe new onset buttock claudication
      was found in 13 (36.1%) of 36 patients with unilateral, and in eight (80%) of 10
      patients with bilateral, internal iliac artery embolization (p = 0.03). Five
      (25%) of 20 men had an erectile dysfunction after the procedure. CONCLUSION:
      Embolization of the internal iliac artery is a safe and efficient procedure that
      increases the applicability for endovascular repair of aortoiliac aneurysms.
      However, buttock claudication and erectile dysfunction are a drawback in a
      substantial number of patients.

PMID- 11517054
TI  - Traumatic common iliac vein disruption treated with an endovascular stent.

PMID- 11517055
TI  - Endovascular repair of abdominal aortic aneurysms: assessment with multislice CT.

PMID- 11517056
TI  - Tunneled peritoneal catheter placement under sonographic and fluoroscopic
      guidance in the palliative treatment of malignant ascites.
AB  - OBJECTIVE: We present a treatment for recurrent, symptomatic ascites in patients
      with malignant disease. This report summarizes our experience with percutaneous
      tunneled peritoneal catheters in 24 patients. SUBJECTS AND METHODS: Of the 40
      consecutive patients who presented with at least four therapeutic paracenteses in
      a 4-week period, 24 patients underwent the percutaneous tunneled procedure. All
      had malignant ascites. RESULTS: All 24 patients had successful insertion of a
      permanent tunneled peritoneal drainage catheter. Eighteen were outpatients and
      six were inpatients. All patients were relieved of their clinical symptoms,
      including abdominal distention and dyspnea, and were relieved of lower extremity
      discomfort. The mean life span after catheter placement was 7.2 weeks. Twenty
      (83%) of the 24 patients were treated at home with their catheters in place.
      Three patients experienced minor complications from bacterial peritonitis, which
      responded to antibiotics. One patient had to have his catheter removed.
      CONCLUSION: Percutaneous placement of specialized tunneled catheters appears to
      be a viable and safe technique in patients who have symptomatic ascites that
      require frequent therapeutic paracentesis for relief of symptoms.

PMID- 11517057
TI  - Imaging features of enterohemorrhagic Escherichia coli colitis.
AB  - OBJECTIVE: The purpose of this article is to define and illustrate the radiologic
      findings in patients with enterohemorrhagic Escherichia coli colitis. CONCLUSION:
      Although not definitive, imaging studies in conjunction with an appropriate
      clinical history can aid in the early diagnosis of E. coli colitis and exclude
      surgical conditions. CT is more sensitive than conventional radiography for
      detection. Contiguous involvement, including the transverse colon, was seen in
      all patients. Because CT is becoming routine in the initial workup of patients
      with acute abdominal pain, it is important for the radiologist to suggest E. coli
      colitis in the proper setting.

PMID- 11517058
TI  - Intussusception into the enteroanastomosis after Billroth II gastrectomy and Roux
      en-Y jejunostomy: sonographic and CT findings.

PMID- 11517059
TI  - Transperineal and transvaginal sonography of perianal inflammatory disease.
AB  - OBJECTIVE: Perianal infection arises in small intersphincteric anal glands
      predominantly located at the dentate line. Documentation of fluid collections and
      the relationship of inflammatory tracts to the sphincter mechanism is important
      for surgical treatment. Transanal sonography for assessment of perianal
      inflammatory disease is limited because placement of the rigid probe into the
      anal canal does not allow assessment of disease in the perineal region. The
      purpose of this study was to validate the use of transperineal sonography in men
      and both transvaginal and transperineal sonography in women for evaluation of
      perianal inflammatory disease. SUBJECTS AND METHODS: Fifty-four patients, 28 men
      and 26 women, were imaged with transperineal and a combination of transperineal
      and transvaginal sonography, respectively. All patients were examined in the
      supine lithotomy and left lateral position with a transvaginal 8-to 4-MHz probe
      or a linear 12- to 7-MHz transducer. All fluid collections, sinus tracts, and
      fistulas were described by their location in relation to the sphincter mechanism
      and perineum. RESULTS: Forty-six of 54 patients had perianal fistulas or sinus
      tracts: 33 transphincteric, seven intersphincteric, and six extrasphincteric.
      Fifteen patients had an associated abscess. In the eight remaining patients,
      there were two anovaginal fistulas, one rectovaginal fistula, one prolapsed
      internal hemorrhoid, two perianal complex masses, and two vascular perianal or
      perirectal inflammatory masses. Twenty-six patients underwent surgical procedures
      involving the anorectal canal or perirectal region, and of these, preoperative
      sonographic findings were confirmed in 22 (85%) of 26 patients. Three patients
      refused surgery, and six are awaiting surgery at this writing. Fifteen patients
      were treated conservatively. CONCLUSION: Transperineal and transvaginal
      sonography are accurate, painless, and cost-effective methods for documenting
      perianal fluid collections and fistulas or sinus tracts or both.

PMID- 11517060
TI  - Predictive value of impaired evacuation at proctography in diagnosing anismus.
AB  - OBJECTIVE: We aimed to determine the positive predictive value of impaired
      evacuation during evacuation proctography for the subsequent diagnosis of
      anismus. SUBJECTS AND METHODS: Thirty-one adults with signs of impaired
      evacuation (defined as the inability to evacuate two thirds of a 120 mL contrast
      enema within 30 sec) during evacuation proctography underwent subsequent
      anorectal physiologic testing for anismus. A physiologic diagnosis of anismus was
      based on a typical clinical history of the condition combined with impaired
      rectal balloon expulsion or abnormal surface electromyogram. RESULTS: Twenty
      eight (90%) of the 31 patients with impaired proctographic evacuation were found
      to have anismus at subsequent physiologic testing. Among the 28 were all 10
      patients who evacuated no contrast medium and all 11 patients with inadequate
      pelvic floor descent, giving evacuation proctography a positive predictive value
      of 90% for the diagnosis of anismus. A prominent puborectal impression was seen
      in only three subjects during proctography, one of whom subsequently showed no
      physiologic sign of anismus. CONCLUSION: Impaired evacuation during evacuation
      proctography is highly predictive for diagnosis of anismus.

PMID- 11517061
TI  - Detection of malignant hepatic tumors: comparison of gadolinium-and ferumoxide
      enhanced MR imaging.
AB  - OBJECTIVE: The purpose of our study was to compare how well gadolinium-enhanced
      and ferumoxide-enhanced MR imaging reveal malignant hepatic tumors. SUBJECTS AND
      METHODS: Both gadolinium-enhanced and ferumoxide-enhanced MR imaging were
      separately performed in 53 patients with a total of 87 malignant hepatic tumors
      (57 hepatocellular carcinomas, 28 metastases, two cholangiocarcinomas). Thirty
      one of the 53 patients had hepatic cirrhosis. Images were reviewed by three
      independent off-site observers. Observer performance was evaluated by means of
      sensitivity, specificity, and receiver operating characteristic curve analyses.
      RESULTS: Gadolinium-enhanced MR imaging outperformed ferumoxide-enhanced MR
      imaging in sensitivity (81% versus 62%, p < 0.01) for malignant-tumor detection.
      Specificity was comparable (94%) between the two types of MR imaging. Area under
      receiver operating characteristic curve (A(z)) value was significantly higher
      with gadolinium-enhanced MR imaging than with ferumoxide-enhanced MR imaging in
      patients overall (A(z) = 0.896 versus 0.805, p < 0.001), in patients with
      cirrhosis (A(z) = 0.907 versus 0.807, p < 0.001), and in patients without
      cirrhosis (A(z) = 0.899 versus 0.834, p < 0.01). The superiority was enhanced in
      the subset of patients with cirrhosis. CONCLUSION: Gadolinium-enhanced MR imaging
      outperforms ferumoxide-enhanced MR imaging in revealing malignant hepatic tumors.
      Gadolinium-enhanced MR imaging is recommended, particularly for patients with
      cirrhosis.

PMID- 11517063
TI  - Multidetector CT of potential right-lobe liver donors.

PMID- 11517064
TI  - Benign schwannoma in the porta hepatis.

PMID- 11517065
TI  - Patterns of recurrence in renal cell carcinoma: manifestations on helical CT.

PMID- 11517066
TI  - Using MR angiography for surgical planning in pelvic kidney renal cell carcinoma.

PMID- 11517067
TI  - CT evaluation of multisystem involvement by oxalosis.

PMID- 11517068
TI  - MR imaging and T2 mapping of femoral cartilage: in vivo determination of the
      magic angle effect.
AB  - OBJECTIVE: The purpose of this study was to perform a quantitative evaluation of
      the effect of static magnetic field orientation on cartilage transverse (T2)
      relaxation time in the intact living joint and to determine the magnitude of the
      magic angle effect on in vivo femoral cartilage. MATERIALS AND METHODS:
      Quantitative T2 maps of the femoral-tibial joint were obtained in eight
      asymptomatic male volunteers using a 3-T magnet. Cartilage T2 profiles (T2 vs
      normalized distance from subchondral bone) were evaluated as a function of
      orientation of the radial zone of cartilage with the applied static magnetic
      field (B(0)). RESULTS: At a normalized distance of 0.3 from bone, cartilage T2 is
      8.6% longer in cartilage oriented 55 degrees to B(0) compared with cartilage
      oriented parallel with B(0). Greater orientation variation is observed in more
      superficial cartilage. At a normalized distance of 0.6, cartilage T2 is 18.3%
      longer. The greatest orientation effect is observed near the articular surface
      where T2 is 29.1% longer at 55 degrees. CONCLUSION: The effect of orientation on
      cartilage T2 is substantially less than that predicted from prior ex vivo
      studies. The greatest variation in cartilage T2 is observed in the superficial
      20% of cartilage. Given the small orientation effect, it is unlikely that the
      "magic angle effect" accounts for regional differences in cartilage signal
      intensity observed in clinical imaging. We hypothesize that regional differences
      in the degree of cartilage compression are primarily responsible for the observed
      regional differences in cartilage T2.

PMID- 11517069
TI  - Articular cartilage and the magic angle effect.

PMID- 11517070
TI  - Adductor insertion avulsion syndrome (thigh splints): spectrum of MR imaging
      features.
AB  - OBJECTIVE: "Thigh splints," also known as the adductor insertion avulsion
      syndrome, is a painful condition affecting the proximal to mid femur at the
      insertion of the adductor muscles of the thigh. Scintigraphic findings in this
      syndrome have been described; we report a spectrum of MR imaging abnormalities
      involving this portion of the femur in a group of patients presenting with hip,
      groin, or thigh pain. CONCLUSION: Symptoms of vague hip, groin, or thigh pain may
      be associated with stress-related changes in the proximal to mid femoral shaft
      (thigh splints). When interpreting MR imaging studies of the pelvis in patients
      presenting with these symptoms, careful attention should be directed to this
      portion of the femur. This is especially important because the findings may be
      subtle, and this region is often at the distal edge of most MR imaging studies of
      the pelvis and hip.

PMID- 11517072
TI  - Helical CT of the cervical spine for trauma patients: a time study.
AB  - OBJECTIVE: The purpose of the study was to determine the time needed to perform a
      helical CT examination of the entire cervical spine. Our study population
      included 156 trauma victims: 100 of these patients underwent CT examination in
      conjunction with a cranial examination; the remaining 56 patients underwent a
      primary cervical examination only. CONCLUSION: Performing a cervical CT
      examination in conjunction with a cranial CT examination added an average of 12
      min to the overall study time. The time for performing a primary cervical
      examination was 11 min on average. These times are approximately half of those
      required for a six-view radiographic evaluation. Helical CT has been suggested as
      a replacement for the more traditional radiographic evaluation of the cervical
      spine in trauma victims. Evidence now exists to support that recommendation.

PMID- 11517073
TI  - Congenital unilateral pulmonary vein atresia: radiologic findings in three adult
      patients.
AB  - OBJECTIVE: The purpose of our study is to describe the radiologic findings of
      adult patients presenting with congenital unilateral pulmonary vein atresia.
      CONCLUSION: Chest radiography in affected patients typically reveals a small
      hemithorax and ipsilateral pulmonary artery as well as ipsilateral septal
      thickening. CT shows, in addition, ground-glass attenuation, the absence of a
      pulmonary vein connection to the left atrium, and abundant mediastinal venous
      collateral vessels. MR imaging is helpful in further characterizing the vascular
      abnormalities. Angiography may help to confirm the diagnosis.

PMID- 11517074
TI  - Cross-sectional CT of strangulating intrapericardial diaphragmatic hernia.

PMID- 11517075
TI  - Giant right coronary aneurysm: CT angiographic and echocardiographic findings.

PMID- 11517077
TI  - Subcutaneous emphysema in a pediatric patient after radiologic placement of a
      percutaneous gastrostomy tube.

PMID- 11517078
TI  - Volumetric brain differences in children with periventricular T2-signal
      hyperintensities: a grouping by gestational age at birth.
AB  - OBJECTIVE: The purpose of this study was to compare both the volumes of the
      lateral ventricles and the cerebral white matter with gestational age at birth of
      children with periventricular white matter (PVWM) T2-signal hyperintensities on
      MR images. The spectrum of neuromotor abnormalities associated with these
      hyperintensities was also determined. MATERIALS AND METHODS: We retrospectively
      reviewed the MR images of 70 patients who were between the ages of 1 and 5 years
      and whose images showed PVWM T2-signal hyperintensities. The patients were
      divided into premature (n = 35 children) and term (n = 35) groups depending on
      their gestational age at birth. Volumetric analysis was performed on four
      standardized axial sections using T2-weighted images. Volumes of interest were
      digitized on the basis of gray-scale densities of signal intensities to define
      the hemispheric cerebral white matter and lateral ventricles. Age-adjusted
      comparisons of volumetric measurements between the premature and term groups were
      performed using analysis of covariance. RESULTS: The volume of the cerebral white
      matter was smaller in the premature group (54 +/- 2 cm(3)) than in the term group
      (79 +/- 3 cm(3), p < 0.0001). The volume of the lateral ventricles was greater
      among the patients in the premature group (30 +/- 2 cm(3)) than among those in
      the term group (13 +/- 1 cm(3), p < 0.0001). Fifty percent of all the premature
      children had spastic diplegia or quadriplegia. Thirty-two percent of all the term
      children had hypotonia. There were patients in both groups whose PVWM T2-signal
      hyperintensities did not correlate with any neuromotor abnormalities but were
      associated with seizures or developmental delays. CONCLUSION: The differences in
      volumetric measurements of cerebral white matter and lateral ventricles in
      children with PVWM T2-signal hyperintensities are related to their gestational
      age at birth. Several neurologic motor abnormalities are found in children with
      such hyperintensities.

PMID- 11517079
TI  - Real-time interactive duplex MR measurements: application in neurovascular
      imaging.
AB  - OBJECTIVE: Real-time interactive duplex MR imaging is a new phase-contrast MR
      imaging technique that enables the quantification and display of flow velocities
      in real time without the need for cardiac gating. We investigated the feasibility
      and reliability of the technique to assess hemodynamic information both in vitro
      and in vivo in the carotid arteries and in the venous sinuses. SUBJECTS AND
      METHODS: Real-time interactive duplex MR measurements (TR/TE, 53/27; flip angle,
      90 degrees; encoding velocity, 100 or 150 cm/sec) were performed in vitro with a
      steady-flow phantom and in 10 healthy volunteers in whom common and internal
      carotid artery velocities were measured. In eight volunteers, velocity
      measurements were also performed in the superior sagittal sinus during both
      normal breathing and hyperventilation. Time-velocity plots were analyzed
      qualitatively and quantitatively and compared with findings from conventional
      segmented k-space phase-contrast MR imaging and Doppler sonography. RESULTS:
      Velocity determinations for real-time duplex MR and conventional phase-contrast
      MR imaging showed an in vitro correlation of 0.99 and an in vivo correlation of
      0.83 (carotid arteries) and 0.76 (venous sinus). Velocity measurements in the
      carotid arteries with real-time MR imaging were significantly lower than those
      obtained with conventional phase-contrast MR (averaged, 7.8%; p = 0.003) or
      sonography (23.7%, p < 0.001), likely because of volume averaging. Small but
      significant velocity changes occurring in the venous sinus during
      hyperventilation were reliably identified with both MR techniques. CONCLUSION:
      Real-time interactive duplex MR imaging can be effectively applied in
      neurovascular imaging to obtain hemodynamic information.

PMID- 11517080
TI  - Diffusion-weighted MR imaging of rim-enhancing brain masses: is markedly
      decreased water diffusion specific for brain abscess?
AB  - OBJECTIVE: This retrospective study investigated the specificity of restricted
      water diffusion for the diagnosis of brain abscess. Two of five rim-enhancing
      brain masses with restricted water diffusion (apparent diffusion coefficient of
      0.79 [10(-3) mm(2)/sec] or less) were brain abscesses, but diagnoses in the other
      cases were metastatic squamous cell carcinoma (two cases) and radiation necrosis.
      CONCLUSION: Although an important diagnostic sign, restricted water diffusion is
      not specific for brain abscess.

PMID- 11517082
TI  - Myelographic complications associated with drug interactions.

PMID- 11517083
TI  - Helical CT angiography of thoracic outlet syndrome.

PMID- 11517084
TI  - Taking care of children.

PMID- 11517085
TI  - Effect of knowledge of actual age on bone age determination.

PMID- 11517086
TI  - Call a spade a spade.

PMID- 11517087
TI  - CT as a cause of cancer: what's old is new again.

PMID- 11517089
TI  - Paradoxical attenuation values in acute aortic dissection.

PMID- 11517090
TI  - Schwannoma of the vagus nerve.

PMID- 11517091
TI  - An unusual central nervous system manifestation of Behcet's disease.

PMID- 11517092
TI  - A fungus by another name: Candida glabrata.

PMID- 11517093
TI  - Medicines for children--the last century and the next.

PMID- 11517094
TI  - Advocating for children's health: a US and UK perspective.

PMID- 11517096
TI  - Breast feeding and cognitive development at age 1 and 5 years.
AB  - AIM: To examine whether duration of breast feeding has any effect on a child's
      cognitive or motor development in a population with favourable environmental
      conditions and a high prevalence of breast feeding. METHODS: In 345 Scandinavian
      children, data on breast feeding were prospectively recorded during the first
      year of life, and neuromotor development was assessed at 1 and 5 years of age.
      Main outcome measures were Bayley's Scales of Infant Development at age 13 months
      (Mental Index, MDI; Psychomotor Index, PDI), Wechsler Preschool and Primary
      Scales of Intelligence (WPPSI-R), and Peabody Developmental Scales at age 5.
      RESULTS: Children breast fed for less than 3 months had an increased risk,
      compared to children breast fed for at least 6 months, of a test score below the
      median value of MDI at 13 months and of WPPSI-R at 5 years. Maternal age,
      maternal intelligence (Raven score), maternal education, and smoking in pregnancy
      were significant confounders, but the increased risk of lower MDI and total IQ
      scores persisted after adjustment for each of these factors. We found no clear
      association between duration of breast feeding and motor development at 13 months
      or 5 years of age. CONCLUSION: Our data suggest that a longer duration of breast
      feeding benefits cognitive development.

PMID- 11517097
TI  - Birth weight and cognitive function at age 11 years: the Scottish Mental Survey
      1932.
AB  - AIMS: To examine the relation between birth weight and cognitive function at age
      11 years, and to examine whether this relation is independent of social class.
      METHODS: Retrospective cohort study based on birth records from 1921 and
      cognitive function measured while at school at age 11 in 1932. Subjects were 985
      live singletons born in the Edinburgh Royal Maternity and Simpson Memorial
      Hospital in 1921. Moray House Test scores from the Scottish Mental Survey 1932
      were traced on 449 of these children. RESULTS: Mean score on Moray House Test
      increased from 30.6 at a birth weight of <2500 g to 44.7 at 4001-4500 g, after
      correcting for gestational age, maternal age, parity, social class, and
      legitimacy of birth. Multiple regression showed that 15.6% of the variance in
      Moray House Test score is contributed by a combination of social class (6.6%),
      birth weight (3.8%), child's exact age (2.4%), maternal parity (2.0%), and
      illegitimacy (1.5%). Structural equation modelling confirmed the independent
      contribution from each of these variables in predicting cognitive ability. A
      model in which birth weight acted as a mediator of social class had poor fit
      statistics. CONCLUSION: In this 1921 birth cohort, social class and birth weight
      have independent effects on cognitive function at age 11. Future research will
      relate these childhood data to health and cognition in old age.

PMID- 11517100
TI  - Changing the US healthcare system.

PMID- 11517098
TI  - Bullying involvement in primary school and common health problems.
AB  - AIMS: To examine the association of direct (e.g. hitting) and relational (e.g.
      hurtful manipulation of peer relationships) bullying experience with common
      health problems. METHODS: A total of 1639 children (aged 6-9 years) in 31 primary
      schools were studied in a cross sectional study that assessed bullying with a
      structured child interview and common health problems using parent reports. Main
      outcome measures were common physical (e.g. colds/coughs) and psychosomatic (e.g.
      night waking) health problems and school absenteeism. RESULTS: Of the children
      studied, 4.3% were found to be direct bullies, 10.2% bully/victims (i.e. both
      bully and become victims), and 39.8% victims. Direct bully/victims, victims, and
      girls were most likely to have physical health symptoms (e.g. repeated sore
      throats, colds, and coughs). Direct bully/victims, direct victims, and year 2
      children were most likely to have high psychosomatic health problems (e.g. poor
      appetite, worries about going to school). Pure bullies (who never got victimised)
      had the least physical or psychosomatic health problems. No association between
      relational bullying and health problems was found. CONCLUSIONS: Direct bullying
      (e.g. hitting) has only low to moderate associations with common health problems
      in primary school children. Nevertheless, health professionals seeing children
      with repeated sore throat, colds, breathing problems, nausea, poor appetite, or
      school worries should consider bullying as contributory factor.

PMID- 11517101
TI  - Recent trends in hospital use by children in England.
AB  - BACKGROUND: Routine hospital statistics for England appear to overestimate use of
      children's wards and include numbers of well newborn babies staying with their
      mothers after delivery ("well babies"). AIM: To review trends in use of
      children's wards excluding data on newborn babies. METHODS: We reviewed routine,
      published, and age stratified data requested from the Department of Health to
      identify separately "well babies" and babies receiving neonatal specialist care
      from admissions (surgical and paediatric) to children's wards. RESULTS: Routine
      reports for paediatric activity contain large numbers of "well babies", (almost
      half the total) as well as babies receiving specialist neonatal care. After
      excluding these, paediatric admissions represent 9.9% of the child population
      aged under 5 years each year (an additional 2.5% are admitted for surgical care).
      Between 1989 and 1997 paediatric admissions rose by 19% and surgical admissions
      fell by 25% with a plateau reached in overall child admissions. There are now
      fewer beds in which children stay for a shorter time and there is more day case
      surgery. Neonatal specialist care work has risen despite a fall in births.
      CONCLUSION: Categories should be established for reporting paediatric episodes on
      children's wards separately from those on neonatal units, with better
      identification of "well babies". When monitoring use of children's inpatient
      facilities or planning new units, care must be taken to separate paediatric data
      on neonatal units from work on children's wards. Children's surgical episodes
      should also be taken into account.

PMID- 11517102
TI  - Triage in the developing world--can it be done?
AB  - AIM: To assess guidelines for the emergency triage, assessment, and treatment
      (ETAT) of sick children presenting to hospitals in the developing world. This
      study pretested the guidelines in Malawi, assessing their performance when used
      by nurses compared to doctors trained in advanced paediatric life support (APLS).
      METHODS: Triage was performed simultaneously by a nurse and assessing doctor on
      2281 children presenting to the under 5s clinic. Each patient was allocated one
      of three priorities, according to the ETAT guidelines. Any variation between
      nurse and assessor was recorded on the assessment forms. RESULTS: Nurses
      identified 92 children requiring emergency treatment and 661 with signs
      indicating a need for urgent medical assessment. One hundred and forty two (6.2%)
      had different priorities allocated by the APLS trained doctor, but these children
      did not tend to need subsequent admission. Eighty five per cent of admissions
      were prioritised to an emergency or urgent category. CONCLUSION: Although there
      are no gold standards for comparison the ETAT guidelines appear to reliably
      select out the majority of patients requiring admission.

PMID- 11517103
TI  - Description of cause of serious illness and outcome in patients identified using
      ETAT guidelines in urban Malawi.
AB  - AIMS: To evaluate the performance of guidelines for emergency triage and
      treatment (ETAT) of children presenting to hospitals in the developing world.
      Part of the study was concerned with the delivery of emergency treatment to the
      sickest group of patients, characterisation of their illness, and outcome.
      METHODS AND RESULTS: A total of 236 children were admitted during the study
      period, 27 of whom died. The three main causes of death were malaria or malaria
      related illness (n = 7), pneumonia (n = 6), and malnutrition (n = 11). Forty
      seven children were categorised as needing emergency treatment. Thirty one had no
      treatment, and eight died; 16 received one or more recommended treatments, of
      whom five died. The main limitations to delivery of immediate care were the lack
      of staff in the department and lack of rapidly available blood.

PMID- 11517104
TI  - The child with a non-blanching rash: how likely is meningococcal disease?
AB  - AIMS: To examine a number of simple clinical features and investigations in
      children with a non-blanching rash to see which predict meningococcal infection.
      METHODS: A total of 233 infants and children up to 15 years of age presenting
      with a non-blanching rash were studied over a period of 12 months. Clinical
      features and laboratory investigations were recorded at presentation. The ability
      of each to predict meningococcal infection was examined. RESULTS: Eleven per cent
      had proven meningococcal infection. Children with meningococcal infection were
      more likely to be ill, pyrexial (>38.5 degrees C), have purpura, and a capillary
      refill time of more than two seconds than non-meningococcal children. Five
      children with meningococcal disease had an axillary temperature below 37.5
      degrees C. No child with a rash confined to the distribution of the superior vena
      cava had meningococcal infection. Investigations were less helpful, although
      children with meningococcal infection were more likely to have an abnormal
      neutrophil count and a prolonged international normalised ratio. No child with a
      C reactive protein of less than 6 mg/l had meningococcal infection. CONCLUSIONS:
      Most children with meningococcal infection are ill, have a purpuric rash, a
      fever, and delayed capillary refill. They should be admitted to hospital and
      treated without delay. Children with a non-blanching rash confined to the
      distribution of the superior vena cava are very unlikely to have meningococcal
      infection. Measurement of C reactive protein may be helpful-no child with a
      normal value had meningococcal infection. Lack of fever at the time of assessment
      does not exclude meningococcal disease.

PMID- 11517105
TI  - Rheumatic fever in a high incidence population: the importance of monoarthritis
      and low grade fever.
AB  - AIMS: To describe the clinical features of rheumatic fever and to assess the
      Jones criteria in a population and setting similar to that in many developing
      countries. METHODS: The charts of 555 cases of confirmed acute rheumatic fever in
      367 patients (97% Aboriginal) and more than 200 possible rheumatic fever cases
      from the tropical "Top End" of Australia's Northern Territory were reviewed
      retrospectively. RESULTS: Most clinical features were similar to classic
      descriptions. However, monoarthritis occurred in 17% of confirmed non-chorea
      cases and 35% of unconfirmed cases, including up to 27 in whom the diagnosis was
      missed because monoarthritis is not a major manifestation. Only 71% and 25% of
      confirmed non-chorea cases would have had fever using cut off values of 38
      degrees C and 39 degrees C, respectively. In 17% of confirmed non-chorea cases,
      anti-DNase B titres were raised but antistreptolysin O titres were normal.
      Although features of recurrences tended to correlate with initial episodes, there
      were numerous exceptions. CONCLUSIONS: Monoarthritis and low grade fever are
      important manifestations of rheumatic fever in this population. Streptococcal
      serology results may support a possible role for pyoderma in rheumatic fever
      pathogenesis. When recurrences of rheumatic fever are common, the absence of
      carditis at the first episode does not reliably predict the absence of carditis
      with recurrences.

PMID- 11517106
TI  - Long term complications of inferior vena cava thrombosis.
AB  - AIM: To evaluate the long term outcome after paediatric inferior vena cava (IVC)
      thrombosis. METHODS: A combined retrospective and prospective study on infants
      and children with IVC thrombosis treated at Aachen and Maastricht University
      Hospitals between 1980 and 1999. RESULTS: Forty patients were enrolled, including
      four with preceding cardiac catheterisation, 18 with central venous saphenous
      lines, and an additional eight with umbilical venous catheters. Six patients died
      within three months of diagnosis; one patient was lost to follow up. Twelve of
      the remaining 33 patients had suffered from limited IVC thrombosis; during follow
      up (for up to nine years) none showed persisting caval obstruction (successful
      thrombolysis, n = 2; spontaneous recanalisation, n = 10). The remaining 21
      patients presented with extensive IVC thrombosis. During follow up (for up to 18
      years) complete restitution was found in only four cases (one thrombolysis, two
      surgery, one spontaneous recanalisation). Persisting iliac and/or caval venous
      obstruction occurred in 17 patients, including six with thrombolysis. Varicose
      veins were found in 12, and post-thrombotic syndrome in seven of these cases.
      According to Kaplan-Meier analysis, 30% of patients with persisting venous
      disease will develop post-thrombotic syndrome within 10 years of the thrombotic
      event. CONCLUSIONS: Infants and children with extensive IVC thrombosis are at
      high risk for persisting venous disease and serious long term complications.
      Prospective trials are urgently needed to establish effective treatment
      strategies and to improve long term prognosis. Central venous catheters,
      contributing to IVC thrombosis in the majority of cases reported here, should be
      inserted only if essential.

PMID- 11517107
TI  - Octreotide therapy: a new horizon in treatment of iatrogenic chyloperitoneum.
AB  - Chyloperitoneum is a rare and challenging complication of abdominal surgery. We
      report a case of iatrogenic chyloperitoneum. Infusion of octreotide, a
      somatostatin analogue, together with total parenteral nutrition followed by
      medium chain triglyceride diet resulted in rapid resolution of chyloperitoneum.
      We believe this to be the first report of successful use of octreotide in
      iatrogenic chyloperitoneum in a child.

PMID- 11517108
TI  - Congenital disorder of glycosylation type Ia (CDG-Ia): phenotypic spectrum of the
      R141H/F119L genotype.
AB  - AIMS: To delineate common and variable features and outcome of children with
      congenital disorder of glycosylation type Ia (CDG-Ia) caused by the frequent
      R141H/F119L PMM2 genotype. METHODS: Clinical data on 25 patients (mean age 7.6
      years, range 0-19) were analysed. RESULTS: All patients had an early presentation
      with severe feeding problems and failure to thrive, hypotonia, hepatic
      dysfunction, inverted nipples, and abnormal subcutaneous fat pads. Eighteen
      patients were hospitalised in the neonatal period. Developmental delay was
      obvious before age 6 months. During the first seven months mean standard
      deviation score (SDS) for weight and length decreased 2.7 (SD = 2) and 2.4 (SD =
      2), respectively. Mental retardation, ataxia, muscular atrophy, and febrile
      seizures were consistent features after infancy. Variable features included
      pericardial effusions, afebrile seizures, and stroke like episodes. Computed
      tomography/magnetic resonance imaging of the brain was normal in two patients
      examined before 4 months of age, but 18 children examined after 3 months of age
      had cerebellar atrophy, and 10 children also had supratentorial atrophy.
      Subsequent imaging showed progression of the cerebellar and supratentorial
      atrophy in eight and four of 10 children, respectively. Mean head circumference
      SDS declined from zero to -1.9 SD from age 3 months to 5 years. Motor ability
      ranged from none to walking with a rolator, and vocabulary ranged from none to
      comprehensible speech. The overall mortality ascribed to CDG-Ia was 18%.
      CONCLUSION: Patients with the R141H/F119L genotype have an early uniform
      presentation including severe failure to thrive, but their functional outcome is
      variable. This genotype may well cause clinical manifestations in the severe end
      of the spectrum of CDG-Ia.

PMID- 11517109
TI  - Hypertension and facial palsy in middle aortic syndrome.
AB  - A female infant presented with facial palsy and was found to be severely
      hypertensive. Plasma renin activity was raised and an angiogram showed middle
      aortic syndrome. This condition is of unknown aetiology, but positive
      antineutrophil cytoplasmic antibodies may indicate a vasculitis which heals by
      intimal fibrosis, causing the observed findings.

PMID- 11517110
TI  - Cholelithiasis in Down's syndrome.
AB  - Cholelithiasis is considered uncommon in infancy, childhood, and adolescence. We
      performed a prospective, controlled study showing that children with Down's
      syndrome have a significantly higher prevalence of cholelithiasis (4.7%) compared
      with controls (0.2%). Clinicians should be aware of the risk of gallstones in
      children with Down's syndrome.

PMID- 11517112
TI  - Infantile chest hamartoma--case outcome aged 11.
AB  - Chest wall hamartoma of infancy is a rare lesion, usually presenting in the first
      year of life. Recent literature has recommended conservative management of
      asymptomatic children, yet most continue to undergo surgical resection
      irrespective of their symptom status. We report a case of spontaneous regression
      of a chest wall hamartoma of infancy, supporting recommendations for conservative
      management in asymptomatic children.

PMID- 11517115
TI  - Towards evidence based medicine for paediatricians.

PMID- 11517113
TI  - Management of hyponatraemia in patients with acute cerebral insults.
AB  - Hyponatraemia is a common finding in patients with acute cerebral insults. The
      main differential diagnosis is between syndrome of inappropriate ADH secretion
      and cerebral salt wasting. Our aim is to review the topic of hyponatraemia in
      patients with acute cerebral insults and suggest a clinical approach to diagnosis
      and management.

PMID- 11517116
TI  - The significance of interleukin 8 in urine.
AB  - AIMS: To assess the implications of detection of interleukin 8 (IL-8) in urine.
      METHODS: IL-8 was measured by immunoassay in all 305 urine samples from children
      aged 0-18.4 years received by our microbiology laboratory during four weeks, with
      a retrospective structured case note audit for all those in whom IL-8, white
      cells, or bacteria were detected. Patients were divided into three groups:
      urinary tract infection (UTI), at least one sample with >/=5 leucocytes x 10(9)/l
      and >/=10(5) cultured bacteria/ml; possible UTI, at least one sample with >/=5
      leucocytes x 10(9)/l or >/=10(5) cultured bacteria/ml but not both; UTI unlikely,
      sample(s) with <5 leucocytes x 10(9)/l and <10(5) cultured bacteria/ml. Medical
      records were sought for all in groups 1 (14/14 found) and 2 (18/21 found) and
      those in group 3 (41/59 found) in whose urine any leucocytes, cultured bacteria,
      or IL-8 were detected. RESULTS: IL-8 was detected in 58/305 samples from 48/264
      patients. IL-8 was detected in at least one urine sample from 13/14 patients with
      confirmed UTI (group 1); in 11/21 patients with possible UTI (group 2), of whom
      two were treated as UTI; and in 23/228 patients without UTI. Using a cut off of
      200 pg/ml, urine IL-8 had a sensitivity of 93% and a specificity of 90% for
      diagnosing UTI. CONCLUSIONS: Urine IL-8 is a sensitive test for UTI, but is
      poorly specific as it is also present in a variety of other infectious and
      inflammatory disorders.

PMID- 11517119
TI  - Evidence based practice in intensive care--light on the horizon?

PMID- 11517118
TI  - Measurement of body fat using leg to leg bioimpedance.
AB  - AIMS: (1) To validate a leg to leg bioimpedance analysis (BIA) device in the
      measurement of body composition in children by assessment of its agreement with
      dual energy x ray absorptiometry (DXA) and its repeatability. (2) To establish a
      reference range of percentage body fat in Hong Kong Chinese children. METHODS:
      Sequential BIA and DXA methods were used to determine body composition in 49
      children aged 7-18 years; agreement between the two methods was calculated.
      Repeatability for the BIA method was established from duplicate measurements.
      Body composition was then determined by BIA in 1139 girls and 1243 boys aged 7-16
      years, who were randomly sampled in eight local primary and secondary schools to
      establish reference ranges. RESULTS: The 95% limits of agreement between BIA and
      DXA methods were considered acceptable (-3.3 kg to -0.5 kg fat mass and -3.9 to
      0.6% body fat). The percentage body fat increased with increasing age. Compared
      to the 1993 Hong Kong growth survey, these children had higher body mass index.
      Mean (SD) percentage body fat at 7 years of age was 17.2% (4.4%) and 14.0% (3.4%)
      respectively for boys and girls, which increased to 19.3% (4.8%) and 27.8% (6.3%)
      at age 16. CONCLUSION: Leg to leg BIA is a valid alternative method to DXA for
      the measurement of body fat. Provisional reference ranges for percentage body fat
      for Hong Kong Chinese children aged 7-16 years are provided.

PMID- 11517120
TI  - Fatty acid amides are putative endogenous ligands for anaesthetic recognition
      sites in mammalian CNS.

PMID- 11517121
TI  - Predictive factors of early morphine requirements in the post-anaesthesia care
      unit (PACU).
AB  - Use of morphine by titration in the post-anaesthesia care unit (PACU) is often
      the first step in postoperative pain management. This approach provides rapid
      analgesia but shows a wide inter-individual variability in morphine requirements
      and may prolong patient stay in the PACU. The aim of this study was to identify
      the patient characteristics, surgical, anaesthetic, and postoperative factors
      predictive of early morphine requirements. The study included 149 patients
      undergoing various non-cardiac surgical procedures under general anaesthesia. In
      the multiple regression analysis of nine variables, only ethnicity (Caucasian),
      emergency surgery, major surgery, surgery exceeding 100 min, and pain score on
      arrival in PACU were predictive factors of morphine requirements. This
      observational study identifies for the first time independent predictive factors
      of morphine requirements in the early postoperative period. Future studies are
      warranted to evaluate the impact of intervention on these factors and any
      resulting improvement in postoperative pain treatment.

PMID- 11517122
TI  - Hormonal and metabolic stress responses after major surgery in children aged 0-3
      years: a double-blind, randomized trial comparing the effects of continuous
      versus intermittent morphine.
AB  - Children aged 0-3 yr were stratified for age and randomized to receive either
      continuous morphine (CM, 10 microg x kg(-1) x h(-1)) with three-hourly placebo
      boluses or intermittent morphine (IM, 30 microg x kg(-1) every 3 h) with a
      placebo infusion for postoperative analgesia. Plasma concentrations of
      epinephrine, norepinephrine, insulin, glucose and lactate were measured before
      and at the end of surgery and 6, 12 and 24 h after surgery. Pain was assessed
      with validated pain scales [the COMFORT scale and a visual analogue scale (VAS)]
      with the availability of additional morphine doses. Minor differences occurred
      between the randomized treatment groups, the oldest IM group (aged 1-3 yr) having
      a higher blood glucose concentration (P=0.003), mean arterial pressure (P=0.02)
      and COMFORT score (P=0.02) than the CM group. In the neonates, preoperative
      plasma concentrations of norepinephrine (P=0.01) and lactate (P<0.001) were
      significantly higher, while the postoperative plasma concentrations of
      epinephrine were significantly lower (P<0.001) and plasma concentrations of
      insulin significantly higher (P<0.005) than in the older age groups.
      Postoperative pain scores (P<0.003) and morphine consumption (P<0.001) were
      significantly lower in the neonates than in the older age groups. Our results
      show that continuous infusion of morphine does not provide any major advantages
      over intermittent morphine boluses for postoperative analgesia in neonates and
      infants.

PMID- 11517123
TI  - Cross-validation of a composite pain scale for preschool children within 24 hours
      of surgery.
AB  - This study was designed to cross-validate a composite measure of the pain scales
      CHEOPS (Children's Hospital of Eastern Ontario Pain Scale), OPS (Objective Pain
      Scale, simplified for parent use by replacing blood pressure measurement with
      observation of body language or posture), TPPPS (Toddler Preschool Postoperative
      Pain Scale) and FLACC (Face, Legs, Activity, Cry, Consolability) in 167 Thai
      children aged 1-5.5 yr. The pain scales were translated and tested for content,
      construct and concurrent validity, including inter-rater and intra-rater
      reliabilities. Discriminative validity in immediate and persistent pain for the
      age groups < or =3 and >3 yr were also studied. The children's behaviour was
      videotaped before and after surgery, before analgesia had been given in the post
      anaesthesia care unit (PACU), and on the ward. Four observers then rated pain
      behaviour from rearranged videotapes. The decision to treat pain was based on
      routine practice and was made by a researcher unaware of the rating procedure.
      All tools had acceptable content validity and excellent inter-rater and intra
      rater reliabilities (intraclass correlation >0.9 and >0.8 respectively).
      Construct validity was determined by the ability to differentiate the group with
      no pain before surgery and a high pain level after surgery, before analgesia
      (P<0.001). The positive correlations among all scales in the PACU and on the ward
      (r=0.621-0.827, P<0.0001) supported concurrent validity. Use of the kappa
      statistic indicated that CHEOPS yielded the best agreement with the routine
      decision to treat pain. The younger and older age groups both yielded very good
      agreement in the PACU but only moderate agreement on the ward. On the basis of
      data from this study, we recommend CHEOPS as a valid, reliable and practical
      tool.

PMID- 11517124
TI  - Volume kinetics of Ringer's solution during induction of spinal and general
      anaesthesia.
AB  - The kinetics of an i.v. infusion of 20 ml x kg(-1) of Ringer's solution over 60
      min was studied in patients undergoing spinal (n=10) and general (n=10)
      anaesthesia. The induction resulted in similar changes in volume kinetic
      parameters in both groups. When a one-volume model was employed (n=8), however,
      the infusion expanded a smaller body fluid space in the four patients who had
      received preoperative enteric lavage (3.3 vs 8.3 litres), which is consistent
      with hypovolaemia. When a two-volume model was statistically justified (n=12),
      the induction reduced the rate of fluid equilibration between a fairly small
      central (V1, mean 1.4 litres) and a peripheral body fluid space by about 50%
      (P<0.01). The kinetic analysis suggested that a rapid fluid load of 350 ml given
      over 2 min just after the induction could possibly prevent arterial hypotension
      because of central hypovolaemia. This was confirmed in five additional patients.

PMID- 11517125
TI  - Patient-controlled analgesia for labour using remifentanil: a feasibility study.
AB  - We have investigated the efficacy and safety of remifentanil in a patient
      controlled analgesia device for labour in 21 women. Remifentanil was available in
      increasing doses (bolus doses 0.25-1.0 microg x kg(-1)) with and without a
      background infusion (0.025-0.05 microg x kg(-1) x min(-1)). A lockout time of 2
      min was used. Thirteen out of 21 (62%) women chose to continue using remifentanil
      up to and during delivery. Nineteen out of 21 (90%) achieved a reduction in pain
      score from baseline. Using a VAS of 0-10 cm the median maximum reduction in pain
      score was 3 cm (range 0-8 cm). There was a significant reduction (P<0.05) from
      baseline pain scores (median= 8 cm) to scores at bolus doses in the range 0.25
      0.5 microg x kg(-1) (median=5 cm). There were no significant reductions in the
      fetal heart rate. Apgar scores and cord blood gas analyses remained within normal
      limits. We conclude that a remifentanil patient-controlled analgesia system
      (bolus doses 0.25-0.5 microg x kg(-1), without a background infusion) may safely
      provide worthwhile, although incomplete, analgesia for labour.

PMID- 11517126
TI  - Quantitative EEG changes associated with loss and return of consciousness in
      healthy adult volunteers anaesthetized with propofol or sevoflurane.
AB  - Significant changes in topographic quantitative EEG (QEEG) features were
      documented during induction and emergence from anaesthesia induced by the
      systematic administration of sevoflurane and propofol in combination with
      remifentanil. The goal was to identify those changes that were sensitive to
      alterations in the state of consciousness but independent of anaesthetic
      protocol. Healthy paid volunteers were anaesthetized and reawakened using
      propofol/remifentanil and sevoflurane/remifentanil, administered in graded steps
      while the level of arousal was measured. Alterations in the level of arousal were
      accompanied by significant QEEG changes, many of which were consistent across
      anaesthetic protocols. Light sedation was accompanied by decreased posterior
      alpha and increased frontal/central beta power. Frontal power predominance
      increased with deeper sedation, involving alpha and, to a lesser extent, delta
      and theta power. With loss of consciousness, delta and theta power increased
      further in anterior regions and also spread to posterior regions. These changes
      reversed with return to consciousness.

PMID- 11517127
TI  - Erythropoietin therapy and preoperative autologous blood donation in children
      undergoing open heart surgery.
AB  - We assessed the feasibility and efficacy of subcutaneous erythropoietin alpha
      (EPO) therapy and preoperative autologous blood donation (ABD) in children
      undergoing open heart surgery. Thirty-nine children were treated consecutively
      with EPO (100 U x kg(-1) s.c. three times a week in the 3 weeks preceding the
      operation and i.v. on the day of surgery) and two ABDs were made (Group 1). As
      controls to compare transfusion requirements, 39 consecutive age-matched patients
      who had undergone open heart surgery during the two preceding years were selected
      (Group 2). In a mean time of 20 (SD 5) days, 96% of scheduled ABDs were performed
      and only three mild vasovagal reactions were observed. The mean volume of
      autologous red blood cells (RBC) collected was 6 (1) ml x kg(-1) and the mean
      volume of autologous RBC produced as a result of EPO therapy before surgery was 7
      (3) ml x kg(-1), corresponding to a 28 (11)% increase in circulating RBC volume.
      The mean volume of autologous RBC collected was not different from that produced
      [6 (1) vs 7 (3) ml x kg(-1), P=0.4]. Allogenic blood was administered to three
      out of 39 children in Group 1 (7.7%) and to 24 out of 39 (61.5%) in Group 2.
      Treatment with subcutaneous EPO increases the amount of autologous blood that can
      be collected and minimizes allogenic blood exposure in children undergoing open
      heart surgery.

PMID- 11517128
TI  - Changes of haemostasis in patients undergoing major abdominal surgery--is there a
      difference between elderly and younger patients?
AB  - Many physiological functions are altered in the elderly. It is not clear whether
      this applies to haemostatic mechanisms in patients undergoing major surgery.
      Twenty-five consecutive patients <60 yr and 25 consecutive patients >70 yr
      scheduled for abdominal surgery for malignancies were included in our study.
      Various standard coagulation variables and specific markers of coagulation were
      serially measured before surgery (baseline), at arrival on the intensive care
      unit (ICU), 4 h after arrival on ICU, and on the morning of the first
      postoperative day. Platelet function was assessed using the Platelet Function
      Analyser PFA-100 with adenosine diphosphate (ADP) as an inductor. Anaesthesia and
      surgery were similar between the elderly (76(3) years) and younger (53(5) years)
      groups. Baseline plasma levels of prothrombin fragments F1+2, thrombin
      antithrombin III (TAT) complex, and D-dimers were significantly different between
      the two groups, indicating thrombin activation and fibrin formation in the
      elderly. Postoperatively, only F1+2 plasma levels were significantly higher in
      the elderly (4.0(0.8) nmol/l) than in the younger patients (2.2(0.9) nmol/l),
      whereas the course of D-dimer and TAT did not differ significantly between the
      two groups. Endothelial-derived markers of coagulation (von Willebrand factor,
      collagen-binding activity of von Willebrand factor) were not different between
      the groups throughout the study period. Platelet function was impaired in the
      elderly compared with the younger patients. It is concluded that elderly patients
      showed more prothrombin activation/thrombin generation and increased fibrinolytic
      activity prior to surgery than younger patients. However, perioperative changes
      of coagulation in the elderly were similar to those seen in younger patients.

PMID- 11517129
TI  - Combination of external chest wall oscillation with continuous positive airway
      pressure.
AB  - We studied the effects of continuous positive airway pressure (CPAP) on pulmonary
      gas exchange during external chest wall oscillation (ECWO), and the relationship
      with obesity, in nine patients with normal body weight (group 'N') and 10 obese
      patients (group 'O'). During ECWO with CPAP 5, PaCO2 decreased in group 'O' (6.0
      (SD 0.8) to 5.6 (0.5) kPa, P<0.05), whereas it increased in group 'N' at all
      levels (P<0.01). Arterial PO(2) (P<0.001) was greater and PaCO2 (P<0.01) less in
      group 'N' during CPPV and ECWO plus CPAP. We also compared the haemodynamic
      effects of ECWO plus CPAP with those of continuous positive pressure ventilation
      (CPPV). ECWO plus CPAP and CPPV were applied for 30 min to 6 ASA III patients.
      Cardiac output (CI 2.7 (0.5) vs 2.1 (0.2) litre x min(-1) x m(-2), P<0.05) and
      stroke volume (SVI 49 (9) vs 32 (6) ml x m(-2), P<0.05) were greater during ECWO
      plus CPAP than with CPPV. ECWO is less effective in obese individuals than in
      those with normal body weight, and the effect of CPAP in overweight individuals
      is small.

PMID- 11517130
TI  - Perianaesthetic risks and outcomes of abdominal surgery for metastatic carcinoid
      tumours.
AB  - Patients with metastatic carcinoid tumours often undergo surgical procedures to
      reduce the tumour burden and associated debilitating symptoms. These procedures
      and anaesthesia can precipitate a life-threatening carcinoid crisis. To assess
      perioperative outcomes, we studied retrospectively the medical records of adult
      patients from 1983 to 1996 who underwent abdominal surgery for metastatic
      carcinoid tumours. Preoperative risk factors, intraoperative complications and
      complications occurring in the 30 days after surgery were recorded. Perioperative
      complications or death occurred in 15 of 119 patients (12.6%, exact confidence
      interval 7.2-19.9). None of the 45 patients who received octreotide
      intraoperatively experienced intraoperative complications compared with eight of
      the 73 patients (11.0%) who did not receive octreotide (P=0.023). The presence of
      carcinoid heart disease and high urinary output of 5-hydroxyindoleacetic acid
      preoperatively were statistically significant risk factors for perioperative
      complications.

PMID- 11517131
TI  - Use of angulated video-intubation laryngoscope in children undergoing manual in
      line neck stabilization.
AB  - Laryngeal views obtained during direct laryngoscopy with and without manual in
      line neck stabilization (MILNS) and during video-assisted intubation with MILNS
      using the angulated video-intubation laryngoscope were assessed in 100 paediatric
      patients (aged 0.25-17.3 yr). Visualization of the larynx (Cormack and Lehane
      score) as well as time taken for video-assisted tracheal intubation by six nurses
      and four resident anaesthetists not experienced in the technique were recorded.
      Cormack and Lehane scores were significantly worse during direct laryngoscopy
      when MILNS was applied. Video-assisted visualization of the larynx during MILNS
      produced scores, which were as good or better than those observed during direct
      laryngoscopy alone. Intubation times ranged from 19-75 s (mean 35 (SD 13.4);
      median 32).

PMID- 11517132
TI  - Temporal dynamics of lung aeration determined by dynamic CT in a porcine model of
      ARDS.
AB  - We used dynamic CT to identify two different time constants of lung aeration and
      their individual contribution to the total increase in cross-sectional lung area
      in healthy and experimentally damaged lungs. In five healthy pigs, inflation and
      deflation between 0 and 50 cm H2O was imposed during dynamic (250 ms/image) CT
      acquisition, and repeated after experimental lung injury by saline lavage. The
      fractional areas of density ranges, which represent aerated lung parenchyma, were
      determined planimetrically, and their time for expansion during the manoeuvre was
      fitted using a bi-exponential model. Thus, two compartments, their sizes, i.e.
      their relative contributions to lung area aerated by the manoeuvre, and their
      specific time constants (tau) were sought. Healthy lungs were characterized best
      by a one-compartmental behaviour with one tau only, both during inflation (median
      tau=0.5 s; range 0.4-0.6 s) and deflation (1.2 s; 1.1-1.3 s). In damaged lungs
      two compartments were found both during inspiration and expiration, with 86% (78
      87%) of the recruitable lung area following a short tau of 0.5 s (0.5-0.6), and
      14% (13-22%) following a longer tau of 9.1 s (8-16.8 s) during inflation. During
      expiration, damaged lungs had a short tau of 0.8 s (0.5-1.0 s) for 94% (84-100%)
      of deflated lung area, and a longer tau of 26.5 s (7.1-34.3 s) for 6% (0-16%). We
      conclude that dynamic CT indicates the relative size and temporal behaviour of
      functional compartments in normal and abnormal lungs. Our findings suggest that
      after lung damage, cyclic ventilation with inspiratory periods of <10 s duration
      will not achieve maximum recruitment for a chosen inspiratory pressure. In ARDS,
      the short expiratory tau predisposes to atelectasis formation if expiratory times
      are >1 s.

PMID- 11517133
TI  - Evolution of cerebral ischaemia induced by thromboembolism in rats detected by
      early sequential MR imaging.
AB  - Thromboembolic stroke appears to evolve in patients in a very complicated manner.
      The present study investigated the evolution of thromboembolic stroke in rats
      (n=9) using a 4.7-T MR imager. Under isoflurane anaesthesia, the rats received
      homologous blood clots into the right internal carotid artery. After
      thromboembolic stroke, lesion volume, which was defined and calculated, based on
      apparent diffusion coefficient maps, tended to increase gradually over the 6 h
      magnetic resonance imaging study. The largest percentage change in lesion volume
      was found at the early stage (40-100 min) of thromboembolism, and showed
      significant correlation with total percentage change in lesion volume (41.6 (SD
      32.8%)) (r=0.77, P<0.05). In conclusion, marked enlargement or diminution of
      lesion volume may be observed at the early stage of thromboembolism.
      Thromboembolic stroke, which can be partly salvaged at the early stage, may
      likely evolve to a lesser extent thereafter.

PMID- 11517134
TI  - Tetanus: a review of the literature.

PMID- 11517135
TI  - Identification of polysubstance abuse in the parturient.
AB  - Illicit drugs are widely used by inner city patients and their use by pregnant
      women has increased in recent years. The aim of this study was to determine the
      prevalence of polysubstance abuse among parturients at our institution who
      received no prenatal care ('unbooked') and to determine the accuracy of the
      Ontrak TesTcup an in vitro immunodiagnostic assay. We prospectively analysed
      urine from 50 'unbooked' parturients and found that 26 (52%) tested positive for
      cocaine. Of these, six patients (23%) were also positive for morphine. All
      TesTcup results were confirmed by the hospital laboratory using alternate
      chemical methods. When comparing TesTcup to the hospital laboratory, there were
      no false positive or negative results. Given the high frequency of concomitant
      opioid abuse in cocaine-abusing parturients, anyone suspected of cocaine abuse
      should be tested for other illicit substances. TesTcup is a clinically accurate
      test that allows the rapid assessment of several drugs of abuse, which may impact
      on anaesthetic care.

PMID- 11517136
TI  - Stress response during weaning after cardiac surgery.
AB  - We compared the effects of weaning using synchronized intermittent mandatory
      ventilation (SIMV) with the use of biphasic positive airway pressure (BIPAP) on
      the stress response, oxygen uptake (VO2) and work of breathing (WOB) in 10
      patients after aortocoronary bypass surgery. All three ventilatory settings were
      investigated in each patient, for example, volume-controlled mechanical
      ventilation immediately before weaning was followed, in randomized order, by both
      SIMV and BIPAP. In addition to routine monitoring of continuous and respiratory
      state, we measured VO2, WOB, and pressure-time product (PTP) as well as the
      plasma concentrations of epinephrine, norepinephrine, ACTH, cortisol,
      vasopressin, and prolactin. Although respiratory rate (f), WOB and PTP were
      greater with both SIMV and BIPAP when compared with control, other variables did
      not change with the ventilatory mode. In conclusion, weaning from mechanical
      ventilation using partial support modes does not affect the postoperative stress
      response in patients who have had uncomplicated cardiac surgery.

PMID- 11517137
TI  - Effects of portal triad clamping on haemodynamic conditions during laparoscopic
      liver resection.
AB  - To evaluate the haemodynamic effects of portal triad clamping (PTC) during
      laparoscopic liver resection, 10 patients without cardiac disease were studied by
      invasive monitoring including a pulmonary artery catheter and were compared with
      a control group of 10 patients undergoing liver resection by laparotomy. During
      laparoscopic surgery, intra-abdominal pressure was kept below 14 mm Hg and minute
      ventilation was adjusted to prevent hypercapnia. Measurements were made before
      PTC (T1), 5 min after PTC (T2) and 5 min after clamp release (T3). During
      clamping with pneumoperitoneum, mean arterial pressure (MAP) remained stable
      (+2%; not significant), systemic vascular resistance (SVR) increased by 37%
      (P<0.01, T2 vs T1) and cardiac index (CI) decreased by 19% (P<0.01, T2 vs T1).
      During laparotomy and clamping, MAP increased by 18% (P<0.01, T2 vs T1), SVR
      increased by 36% (P<0.01, T2 vs T1) and CI decreased by 9% (not significant). We
      were unable to demonstrate a difference in haemodynamic changes during clamping
      with pneumoperitoneum vs the open surgical technique, but in a small number of
      patients this lack of difference could have been a result of inadequate
      statistical power. The haemodynamic changes that we found were well tolerated in
      these patients, who had normal cardiac function.

PMID- 11517138
TI  - Arterial and mixed venous xenon blood concentrations in pigs during wash-in of
      inhalational anaesthesia.
AB  - There are no data available on the kinetics of blood concentrations of xenon
      during the wash-in phase of an inhalation anaesthesia aiming at 1 MAC end
      expiratory concentration. Therefore, we anaesthetized eight pigs with continuous
      propofol and fentanyl and measured arterial, mixed venous and end-expiratory
      xenon concentrations by gas chromatography-mass spectrometry 1, 2, 3, 4, 5, 7,
      10, 15, 20, 30, 60 and 120 min after starting the anaesthetic gas mixture [67%
      xenon/33% oxygen; 3 litre x min(-1) during the first 10 min, thereafter minimal
      flow with 0.48 (SD 0.03) litre x min(-1)]. End-expiratory xenon concentrations
      plateaued (defined as <5% change from the preceding value) at 64 (6) vol% after 7
      min, and arterial and mixed venous xenon concentrations after 5 and 15 min
      respectively. The highest arterio-venous concentration difference occurred after
      3 min. Using the Fick principle, we calculated a mean xenon uptake of 3708 (829)
      and 9977 (3607) ml after 30 and 120 min respectively.

PMID- 11517139
TI  - Haemodynamic effects of three doses of dihydroergotamine during spinal
      anaesthesia.
AB  - We performed a randomized study comparing the haemodynamic effects of three doses
      of the vasopressor dihydroergotamine (DHE) (5, 10 and 15 microg x kg(-1)) in 30
      ASA 1 and 2 patients, aged 53-87 yr, undergoing spinal anaesthesia. Non-invasive
      systolic arterial pressure (SAP), heart rate and central venous pressure (CVP)
      were recorded continuously for 25 min. Intravenous fluids were withheld during
      this period. All three doses of DHE reversed the lowering effects of spinal
      anaesthesia on SAP and CVP (P<0.0001), and these effects were smooth in onset and
      sustained. Whereas the lowest (5 microg x kg(-1)) dose restored SAP and CVP to
      near prespinal values, the higher (10 and 15 microg x kg(-1)) doses resulted in
      above-baseline increases in SAP of 7% and in CVP of 2.7 cm H2O (P<0.05). The
      haemodynamic profile of DHE makes it a useful agent for managing hypotension
      during spinal anaesthesia. A dose of 5-10 microg x kg(-1) is recommended.

PMID- 11517140
TI  - Prophylactic ondansetron does not improve patient satisfaction in women using PCA
      after Caesarean section.
AB  - Eighty-one consenting women undergoing elective Caesarean section under spinal
      anaesthesia were randomly divided into two groups. In Group O patients,
      ondansetron 4 mg was given intravenously at the end of the surgery and 8 mg added
      to the morphine solution in the PCA syringe. Patients in Group P received only
      morphine via PCA syringe. Analgesia and nausea were measured until PCA was
      discontinued 24 h after the operation. Women in the two groups were similar with
      respect to age, duration of use of the PCA, amount of morphine used, previous
      history of PONV, and incidence of motion sickness and morning sickness during the
      current pregnancy. The number of women who complained of nausea and those needing
      rescue antiemetic medication was significantly less in Group O. However, there
      was no statistically significant difference between the two groups in the
      patient's perception of the control of nausea and their overall satisfaction. It
      was noted that PONV was more frequent among women who had significant morning
      sickness during early pregnancy and ondansetron was beneficial in reducing PONV
      in these women. Although the ondansetron reduced the incidence of PONV and the
      need for further antiemetic medication, this did not affect patient's
      satisfaction regarding their postoperative care.

PMID- 11517141
TI  - Onset of propofol-induced burst suppression may be correctly detected as
      deepening of anaesthesia by approximate entropy but not by bispectral index.
AB  - The bispectral index (BIS) is a complex EEG variable that combines several
      disparate descriptors of the EEG into a single value. Approximate entropy is a
      novel EEG measure that quantifies the regularity of a data time series such as
      EEG. We report two patients in which the EEG effect of propofol was quantified
      very similarly by BIS and approximate entropy. However, at the beginning of burst
      suppression of the EEG, BIS did not indicate an increased anaesthetic drug
      effect, while approximate entropy did.

PMID- 11517142
TI  - Hydrothorax: an unexpected complication after laparoscopic myomectomy.
AB  - We report a case of hydrothorax as a complication of laparoscopic myomectomy in
      an otherwise healthy woman. The most likely cause of the patient's hydrothorax
      was irrigation fluid moving from the peritoneal cavity into the pleural space via
      defects in the diaphragm. Anaesthesists and surgeons should consider hydrothorax
      as a potential complication in any patient undergoing laparoscopy.

PMID- 11517143
TI  - Transient right phrenic nerve palsy associated with central venous
      catheterization.
AB  - An 85-yr-old woman with advanced sigmoid colon cancer developed right phrenic
      nerve palsy following central venous catheterization for preoperative nutritional
      and fluid balance improvement. The central venous catheter was successfully
      placed via the left subclavian vein at the first attempt. Blood returned freely
      through the catheter. The chest x-ray film taken immediately after the
      catheterization showed the proper placement of the catheter, but it revealed a
      significant right hemidiaphragmatic elevation indicating phrenic nerve palsy. A
      chest computed tomography scan and bronchoscopy were normal. As the patient did
      not complain of dyspnoea and vital signs were normal, tumour resection was
      performed. The operative and postoperative course was uneventful. The chest x-ray
      film after the surgery still showed the elevation of the right hemidiaphragm. It
      resolved completely within 3 days of withdrawing the central venous catheter by 3
      cm on the fourth postoperative day. We concluded the likely cause of the phrenic
      nerve palsy was that the catheter tip impinged upon the thin venous wall and
      compressed the phrenic nerve running alongside the superior vena cava.

PMID- 11517144
TI  - Spinal cord injury caused by direct damage by local anaesthetic infiltration
      needle.
AB  - We describe a case of spinal cord injury caused by direct trauma from a local
      anaesthetic infiltration needle. During local anaesthetic infiltration before
      placement of an epidural catheter, the patient suddenly rolled over onto her
      back, causing the infiltrating needle to advance all the way to its hub. She
      immediately showed signs of spinal cord injury, confirmed by MRI scan. However,
      her neurological status gradually improved, and on discharge she was able to
      walk, with a sensory deficit localized to her left foot.

PMID- 11517145
TI  - Tracheobronchopathia osteoplastica: incidental finding at tracheal intubation.
AB  - Subglottic papillomatous growths were observed on routine tracheal intubation for
      a scheduled colorectal procedure. Fibreoptic bronchoscopy revealed that the
      lesions extended down to the carina and into the main bronchi. The diagnosis of
      tracheobronchopathia osteoplastica was made after subsequent bronchoscopy and
      biopsy in the post-operative period. A brief review of this rare benign condition
      is given.

PMID- 11517146
TI  - Cognitive decline following cardiac surgery.

PMID- 11517147
TI  - Starvation amidst plenty--rickets and hypercalcemia in calcium receptor knockout
      mice.

PMID- 11517148
TI  - The expression of the sodium/iodide symporter is up-regulated in the thyroid of
      fetuses of iodine-deficient rats.
AB  - Is the fetal thyroid already capable to increase its iodide uptake in response to
      iodine deficiency? To answer this question, we analyzed the expression of the
      Na(+)/I(-) symporter and several other genes in the thyroid of rat fetuses at 21
      d of gestation from control mothers presenting a mild or more severe iodine
      deficiency. Female rats were placed on a low iodine diet, not supplemented, or
      supplemented with iodide or perchlorate for 3 months. The maternal and fetal
      thyroidal iodide uptake was measured 24 h after injection of 10 microCi Na (125)I
      into the dams. The absolute iodide uptake of the maternal thyroid was unchanged
      in a low iodine diet, not supplemented, compared with one supplemented with
      iodide. In contrast, the fetal thyroid absolute iodide uptake of a low iodine
      diet, not supplemented, and one supplemented with perchlorate was decreased by
      70% and 95% compared with that supplemented with iodide. Na(+)/I(-) symporter
      mRNA was detected in the fetal thyroid of supplemented with iodide and increased
      about 2- and 4- fold in the thyroid of fetuses from a low iodine diet, not
      supplemented, and one supplemented with perchlorate, respectively. Na(+)/I(-)
      symporter expression was induced in the fetal side of the placenta in both a low
      iodine diet, not supplemented, and one supplemented with perchlorate; in
      contrast, Na(+)/I(-) symporter mRNA was never detected in the maternal side of
      the placenta. Fetal thyroid thyroglobulin and type I deiodinase mRNA contents
      were only significantly increased with a diet supplemented with perchlorate.
      Glucose transporter 4 mRNA was decreased in the fetal thyroid of both a low
      iodine diet, not supplemented, and one supplemented with perchlorate compared
      with one supplemented with iodide. In conclusion, although the up-regulation of
      Na(+)/I(-) symporter expression in fetal thyroid and placenta in the low iodine
      diet, not supplemented group did not lead to restoration of a normal absolute
      iodide uptake, our data show that all adaptive and/or defending mechanisms
      against iodine deficiency are already present in the fetus.

PMID- 11517149
TI  - Dexamethasone during late gestation exacerbates peripheral insulin resistance and
      selectively targets glucose-sensitive functions in beta cell and liver.
AB  - We examined whether low-dose dexamethasone administration during late pregnancy
      modifies hepatic and/or peripheral insulin action or glucose-stimulated insulin
      secretion. Dexamethasone (100 microg/kg maternal body weight/d) was administered
      via an osmotic minipump from d 14--19 of gestation. Maternal glucose-insulin
      homeostasis was assessed on d 19 of pregnancy in the postabsorptive state.
      Insulin secretion and glucose tolerance was assessed after iv glucose, and
      insulin action examined during insulin infusion at euglycemia. Dexamethasone
      treatment during late pregnancy elicited fasting hyperinsulinaemia (by 88%; P <
      0.001) and hyperglycaemia (by 20%; P < 0.05), and enhanced endogenous glucose
      production (by 29%; P < 0.001). Insulin secretion and rates of glucose
      disappearance after iv glucose were greatly impaired (by 44% and 39%
      respectively; P < 0.05). Suppression of endogenous glucose production by insulin
      was enhanced by dexamethasone treatment, but insulin's ability to promote glucose
      clearance was diminished. We demonstrate that excess maternal glucocorticoids
      during late pregnancy impairs glucose-stimulated insulin secretion and insulin
      simulated glucose clearance but enhances insulin's ability to suppress endogenous
      glucose production. The data also indicate that elevated maternal glucocorticoids
      impair adaptations of the endocrine pancreas to pregnancy in vivo in that insulin
      hypersecretion in response to deteriorating peripheral insulin action is no
      longer apparent, leading to impaired glucose tolerance.

PMID- 11517150
TI  - Distribution of chimeric IGF binding protein (IGFBP)-3 and IGFBP-4 in the rat
      heart: importance of C-terminal basic region.
AB  - IGF binding proteins-3 and -4, whether given in the perfused rat heart or given
      iv in the intact animal, cross the microvascular endothelium of the heart and
      distribute in subendothelial tissues. IGF binding protein-3, like IGF-I/II,
      localizes in cardiac muscle, with lesser concentrations in CT elements. In
      contrast, IGFBP-4 preferentially localizes in CT. In this study, chimeric IGF
      binding proteins were prepared in which a basic 20-amino-acid C-terminal region
      of IGF binding protein-3 was switched with the homologous region of IGF binding
      protein-4, and vice-versa, to create IGF binding protein-3(4) and IGF binding
      protein-4(3). Perfused IGF binding protein-3(4) behaved like IGF binding protein
      4, localizing in connective tissue elements, whereas IGF binding protein-4(3) now
      localized in cardiac muscle at concentrations identical to perfused IGF binding
      protein-3. To determine whether these small mutations altered the affinity of the
      chimera for cells, the ability of (125)I-IGF binding protein-3(4) and (125)I-IGF
      binding protein-4(3) to bind to microvascular endothelial cells was determined
      and compared with IGF binding protein-3. IGF binding protein-3(4) retained 15% of
      the binding capacity of IGF binding protein-3, whereas IGF binding protein-4(3)
      bound to microvessel endothelial cells with higher affinity and greater total
      binding than that of IGF binding protein-3. We conclude that small changes in the
      C-terminal basic domain of IGF binding protein-3 and the corresponding region of
      IGF binding protein-4 can alter their affinity for cultured cells and influence
      their tissue distribution in the rat heart.

PMID- 11517151
TI  - Dominant negative ER induces apoptosis in GH(4) pituitary lactotrope cells and
      inhibits tumor growth in nude mice.
AB  - The ER plays an important role in the proliferation and differentiation of
      lactotrope tumor cells. GH(4) cells were infected with adenoviral vectors
      (AdL540Q and Ad1-536) to investigate the ability of dominant negative ER mutants
      to affect the regulation of gene expression and cell growth by endogenous ER. The
      dominant negative mutants suppressed estradiol stimulation of an estrogen
      responsive reporter gene and the PRL promoter in these cells. AdL540Q or Ad1--536
      infection also inhibited GH(4) cell growth and induced apoptosis, increasing the
      expression of the proapoptotic Bax protein and decreasing the expression of
      antiapoptotic Bcl-2. AdwtER-infected cells also showed decreased Bcl-2 protein.
      E2-induced activation of p38 MAPK, an enzyme that may participate in apoptosis,
      was observed in cells infected with AdwtER, AdL540Q, and Ad1--536. Consistent
      with the apoptotic effects in vitro, infection of GH(4) cells with AdL540Q or Ad1
      -536 inhibited the ability of the cells to form tumors in nude mice. These
      results indicate that dominant negative ER mutants induce apoptosis of GH(4)
      cells and suppress tumor formation and development. The delivery of dominant
      negative ERs by adenoviral vectors may provide an alternative modality for the
      targeted therapy of pituitary lactotrope adenomas and other estrogen-responsive
      tumors.

PMID- 11517152
TI  - The effect of GHRH on somatotrope hyperplasia and tumor formation in the presence
      and absence of GH signaling.
AB  - Excessive GHRH stimulation leads to somatotrope hyperplasia and, ultimately,
      pituitary adenoma formation in the metallothionein promoter-driven human GHRH
      (hGHRH) transgenic mouse. This pituitary phenotype is similar to that observed in
      humans with ectopic production of GHRH. In both mice and man, GHRH
      hyperstimulation also results in dramatic increases in circulating GH and IGF-I.
      To determine whether GH/IGF-I modulates the development and growth rate of GHRH
      induced pituitary tumors, pituitary growth and histology were evaluated in mice
      generated from cross-breeding metallothionein promoter-driven hGHRH transgenic
      mice with GH receptor binding protein (GHR) gene disrupted mice (GHR(-/-)).
      Expression of the hGHRH transgene in 2-month-old GHR intact (GHR(+)) mice
      resulted in the doubling of pituitary weight that was largely attributed to an
      increase in the number of GH-immunopositive cells. Pituitary weight of GHR(+)
      hGHRH mice did not significantly change between 2 and 6 months of age, whereas at
      12 months, weights increased up to 100-fold those of GHR(+) pituitaries, and 70%
      of the glands contained grossly visible adenomas. All adenomas stained positively
      for GH, whereas some showed scattered PRL staining. Pituitaries of GHR(-/-) mice
      were half the size of those of GHR(+) mice. Although reduced in size, the
      histological features of GHR(-/-) mouse pituitaries were suggestive of
      somatotrope hyperplasia. Despite evidence of somatotrope hyperplasia, pituitaries
      from GHR(-/-) mice as old as 28 months of age were similar in size to those of 2
      month-old mice and did not show signs of adenoma formation. Expression of the
      hGHRH transgene in GHR(-/-) mice did not significantly increase pituitary size
      between 2 and 6 months of age. However, at 12 months the majority of GHR(-/-),
      hGHRH pituitaries developed adenomas with mean pituitary weight and histological
      features similar to those of GHR(+), hGHRH mice. These observations demonstrate
      that intact GH signaling is not required for GHRH tumor formation. Although the
      majority of GHR(+), hGHRH and GHR(-/-), hGHRH pituitaries developed tumors by 12
      months of age, a small subset remained morphologically indistinct from those at 2
      months of age. These observations taken together with the fact that overt tumor
      formation is preceded by a static pituitary growth phase between 2 and 6 months,
      indicates that protective mechanisms are in place to maintain pituitary mass
      despite hGHRH hyperstimulation.

PMID- 11517153
TI  - Fasting, leptin treatment, and glucose administration differentially regulate
      Y(1) receptor gene expression in the hypothalamus of transgenic mice.
AB  - NPY is a potent orexigenic signal and represents a key component of targets
      through which leptin exerts a regulatory restraint on body adiposity. Part of the
      orexigenic effects of NPY are mediated by hypothalamic NPY-Y(1) receptors. Here
      we studied the effect of fasting, leptin, and glucose administration on Y(1)
      receptor gene expression using a transgenic mouse model carrying a mouse Y(1)
      receptor/LacZ fusion gene. Transgene expression was determined by quantitative
      analysis of beta-galactosidase histochemical staining in the paraventricular,
      arcuate, ventromedial, and dorsomedial hypothalamic nuclei and in the medial
      amygdala, as a control region. Food deprivation for 72 h decreased transgene
      expression in the paraventricular nucleus but not in the arcuate nucleus. Leptin
      treatment, that was per se ineffective, counteracted the decrease of transgene
      expression induced in the paraventricular nucleus by 72 h fasting. Supplementing
      the drinking water with 10% glucose increased beta-galactosidase expression both
      in the paraventricular nucleus and arcuate nucleus of control mice. Finally, none
      of the treatments altered transgene expression in the dorsomedial hyphothalamic,
      ventromedial, and amygdaloid nuclei. Results suggest that changes in energetic
      balance affect Y(1) receptor expression in the paraventricular and arcuate nuclei
      and that leptin regulates the NPY-Y(1) system in the paraventricular nucleus.
      Different regulatory signals might modulate the NPY-Y(1) transmission in the
      dorsomedial hyphothalamic and ventromedial hyphothalamic nuclei.

PMID- 11517154
TI  - Inhibition of isoproterenol-induced lipolysis in rat inguinal adipocytes in vitro
      by physiological melatonin via a receptor-mediated mechanism.
AB  - Because the pineal hormone melatonin has been implicated in affecting adiposity
      in rats and fatty acid transport in certain rat tumor models, we tested whether
      melatonin regulates lipolysis in a normal cell system in vitro. Adipocytes were
      isolated from the inguinal fat pads (i.e. sc fat) of Sprague Dawley male rats
      during mid-light phase. Lipolysis was stimulated with isoproterenol (3 microM),
      and cells were incubated for 4 h in the presence or absence of a physiological
      circulating concentration of melatonin (1 nM). Lipolysis was measured by
      determining the amount of glycerol present in the incubation buffer, expressed as
      nmol glycerol/mg cellular fatty acid. We observed a 20- to 30-fold stimulation of
      basal lipolysis by isoproterenol, and this stimulation was inhibited 50--70% by
      melatonin. Melatonin exhibited this effect over a wide range of concentrations
      tested (100 pM-1 microM) with an IC(50) of approximately 500 pM. The effect by
      melatonin (1 nM) was completely blocked by pertussis toxin (50 ng/ml), by 8-bromo
      cAMP (10 nM), and by the melatonin receptor antagonist S-20928 (1 nM). These
      results suggest that the antilipolytic effect occurs through one of the G(i)
      protein-coupled melatonin receptors because we have shown that both the mt(1)
      (Mel 1a) and MT(2) (Mel 1b) melatonin receptors are expressed in inguinal
      adipocytes. Melatonin inhibition of lipolysis was not observed in adipocytes
      isolated from rat epididymal fat pads (i.e. visceral fat), even though these
      cells also express both the mt(1) and MT(2) receptors. The results indicate that
      physiological circulating concentrations of melatonin inhibit isoproterenol
      induced lipolysis in rat adipocytes via a G protein-coupled melatonin receptor
      mediated signal transduction pathway in a site-specific manner.

PMID- 11517155
TI  - A-ring reduced metabolites of 19-nor synthetic progestins as subtype selective
      agonists for ER alpha.
AB  - It has previously been demonstrated that 19-nor contraceptive progestins undergo
      in vivo and in vitro enzyme-mediated A-ring double bond hydrogenation.
      Bioconversion of 19-nor progestins to their corresponding tetrahydro derivatives
      results in the loss of progestational activity and acquisition of estrogenic
      activities and binding to the ER. Herein, we report subtype-selective differences
      in ligand binding and transcriptional potency of nonphenolic synthetic 19-nor
      derivatives between ER alpha and ER beta. In this study, we have examined both ER
      and PR-mediated transcriptional activity of a number of A-ring chemically
      reduced derivatives of norethisterone and Gestodene. Double bond hydrogenation
      decreased the transcriptional potency of norethisterone and Gestodene through
      both PR isoforms with a 100- to 1,000-fold difference, respectively. In terms of
      the effects of norethisterone and Gestodene and their corresponding 5 alpha
      dihydro (5 alpha-norethisterone and 5 alpha-Gestodene), or 3 alpha,5 alpha
      tetrahydro or 3 beta,5 alpha-tetrahydro derivatives (3 alpha,5 alpha
      norethisterone/3 alpha,5 alpha-Gestodene and 3 beta,5 alpha
      norethisterone/3beta,5 alpha-Gestodene, respectively) on estrogen-mediated
      transcriptional regulation, the 3 beta,5 alpha-tetrahydro derivatives of both
      norethisterone and Gestodene showed the highest induction when HeLa cells were
      transiently transfected with an expression vector for ER alpha. This activity
      could be inhibited with tamoxifen. These compounds did not activate gene
      transcription via ER beta, and none of them showed antagonistic activities
      through either ER subtype. The 3 beta,5 alpha-tetrahydro derivatives of both
      norethisterone and Gestodene were active in other cells in addition to HeLa cells
      and activated reporter expression through the oxytocin promoter. In summary, two
      ER alpha selective agonists have been identified. These compounds, with ER alpha
      vs. ER beta selective agonist activity, may be useful in evaluating the distinct
      role of these receptors as well as in providing useful insights into ER action.

PMID- 11517156
TI  - Androgens suppress osteoclast formation induced by RANKL and macrophage-colony
      stimulating factor.
AB  - Androgen deficiency in males leads to an increase in osteoclastic bone resorption
      and a progressive decrease in bone mineral density. In the current studies, we
      examined the ability of 5 alpha-dihydrotestosterone to suppress osteoclast
      formation induced by receptor activator of NF-kB ligand (RANKL) and macrophage
      colony stimulating factor in vitro. 5 alpha-Dihydrotestosterone suppressed the
      differentiation of bone marrow monocytes into osteoclasts from both sham-operated
      and orchidectomized mice. Androgen deficiency also led to an increase in the
      number of hematopoietic precursors capable of forming osteoclasts and increased
      the relative responsiveness of these cells to androgens in vitro. Interestingly,
      E2 was as effective as 5 alpha-dihydrotestosterone in suppressing osteoclast
      formation in bone marrow monocytes from both sham and orchidectomized mice. As
      with bone marrow monocytes, 5 alpha-dihydrotestosterone also suppressed RANKL
      induced osteoclast formation in the monocyte-macrophagic cell line RAW264.7. In
      RAW264.7 cells, androgens appear to block RANKL-induced osteoclast formation
      through selective regulation of c-JUN: Accordingly, 5 alpha-dihydrotestosterone
      suppressed RANKL-induced c-Jun N-terminal kinase activation and reduced c-Jun
      expression levels. These effects resulted in a reduction in RANKL-induced
      activator protein-1 DNA binding activity and a corresponding suppression in
      activator protein-1-mediated transcriptional activation. These studies indicate
      that both E and androgens can suppress osteoclast formation via a direct, stromal
      cell-independent action on osteoclast precursors to block key transcription
      factors such as c-Jun essential for osteoclast differentiation.

PMID- 11517157
TI  - Caspase-3 and caspase-activated deoxyribonuclease are associated with testicular
      germ cell apoptosis resulting from reduced intratesticular testosterone.
AB  - The purpose of the present study was to examine the possible involvement of
      caspase-3 and caspase-activated deoxyribonuclease in rat testicular germ cell
      apoptosis resulting from reduced intratesticular testosterone concentration.
      Adult Sprague Dawley rats received LH-suppressive testosterone- and estradiol
      filled SILASTIC capsules of 2.5 and 0.1 cm, respectively, a regimen known to
      rapidly reduce testosterone production by the testes and to produce azoospermia
      within 8 wk. Germ cell internucleosomal DNA cleavage increased compared with
      control levels by 1 wk postimplantation and increased further through 4 wk. In
      situ terminal deoxynucleotidyltransferase-mediated deoxy-UTP nick end labeling
      revealed that spermatocytes represented the predominant apoptotic cell type.
      Modest immunoreactivity for active caspase-3 was localized to the cytoplasm or
      perinuclear region of the germ cells of control testes. After testosterone and
      estradiol administration, however, intense staining for caspase-3 was localized
      to the nuclei of spermatocytes. Western blotting revealed significantly increased
      caspase-3 cleavage (activation) in nuclei isolated from germ cells after rats
      were administered testosterone and estradiol. Cleavage of the caspase-3 substrate
      protein, poly(ADP-ribose) polymerase, was seen after testosterone and estradiol
      treatment. Additionally, the caspase-activated deoxyribonuclease protein content
      was significantly increased in germ cells after rats were administered
      testosterone and estradiol, and caspase-activated deoxyribonuclease
      immunoreactivity was localized to the nuclei of apoptotic spermatocytes. Taken
      together, these results indicate that germ cell apoptosis resulting from a
      reduced intratesticular testosterone concentration is caspase-3 activation
      dependent and suggest that the translocation of active caspase-3 and caspase
      activated deoxyribonuclease to the nucleus may be involved in the induction of
      germ cell apoptosis.

PMID- 11517158
TI  - Butyrate, a histone deacetylase inhibitor, activates the human IGF binding
      protein-3 promoter in breast cancer cells: molecular mechanism involves an
      Sp1/Sp3 multiprotein complex.
AB  - Specific cell growth stimulators and inhibitors regulate IGF binding protein-3
      (IGFBP-3), where in turn IGFBP-3 mediates their biological effects. The molecular
      mechanism(s) by which these factors regulate IGFBP-3 are unknown. Sodium
      butyrate, a histone deacetylase inhibitor causing growth arrest and
      differentiation, increases IGFBP-3 expression. We investigated the molecular
      mechanism of this induction using an IGFBP-3 promoter reporter system in MCF-7
      and Hs578T breast cancer cells. IGFBP-3 promoter activity was induced up to 40
      fold following a 24-h treatment with sodium butyrate and 46-fold in cells treated
      with trichostatin A, a pure histone deacetylase inhibitor. Deletion analysis of
      the IGFBP-3 promoter identified key sodium butyrate-responsive element(s) to a 45
      bp region containing consensus binding sites for Sp1 and activating protein-2.
      Sp1 binding to the Sp1 site and Sp3 to the activating protein-2/GA-box played a
      functional role in sodium butyrate's activation of the IGFBP-3 promoter, however,
      with no change in binding direct sodium butyrate regulation was attributed to
      cofactors. The histone acetyltransferase p300 and histone deacetylase-1 were
      identified in multiprotein complexes containing DNA bound Sp1 and Sp3, with p300
      accumulating following sodium butyrate treatment. Taken together, these data
      suggest that sodium butyrate increases IGFBP-3 expression by activating the IGFBP
      3 promoter via an Sp1/Sp3 multiprotein complex, a mechanism that may be important
      for other key regulators of IGFBP-3.

PMID- 11517159
TI  - Stage-dependent regulation of ovarian pituitary adenylate cyclase-activating
      polypeptide mRNA levels by GnRH in cultured rat granulosa cells.
AB  - The present study was designed to test whether GnRH regulates pituitary adenylate
      cyclase-activating polypeptide mRNA levels in a stage-dependent manner during
      follicle development in the rat ovary. The granulosa cells of preovulatory and
      immature follicles obtained from PMSG- and estrogen-treated rats, respectively,
      were cultured in serum-free conditions in the presence of various hormones. GnRH
      receptor mRNA expression was detected in both preovulatory and immature granulosa
      cells and was down-regulated by gonadotropins. Treatment of preovulatory
      granulosa cells with GnRH agonist stimulated pituitary adenylate cyclase
      activating polypeptide mRNA levels in a dose-dependent manner. In situ
      hybridization analysis of cultured preovulatory follicles revealed that GnRH
      induced pituitary adenylate cyclase- activating polypeptide signals were detected
      in granulosa cells, but not thecal cells. In immature granulosa cells,
      cotreatment with GnRH agonist suppressed FSH-stimulated pituitary adenylate
      cyclase-activating polypeptide mRNA levels in a dose-dependent manner, whereas
      treatment with GnRH alone had no effect. Furthermore, treatment with GnRH
      antagonist inhibited LH-induced pituitary adenylate cyclase-activating
      polypeptide gene expression in preovulatory granulosa cells, whereas it
      stimulated FSH-induced pituitary adenylate cyclase-activating polypeptide gene
      expression in immature granulosa cells. Interestingly, GnRH-stimulated pituitary
      adenylate cyclase-activating polypeptide mRNA levels in preovulatory granulosa
      cells was inhibited by arachidonyltri fluoromethyl ketone, an inhibitor of
      phospholipase A(2), but not by an inhibitor of protein kinase A or C. Lastly,
      treatment of preovulatory follicles with pituitary adenylate cyclase-activating
      polypeptide antagonist suppressed GnRH-stimulated progesterone production during
      6--9 h of culture. Taken together, these results demonstrate the stage-dependent
      regulation of pituitary adenylate cyclase-activating polypeptide mRNA levels by
      GnRH, the stimulatory and inhibitory effect in granulosa cells of preovulatory
      and immature follicles, respectively.

PMID- 11517160
TI  - STAT5b is required for GH-induced liver IGF-I gene expression.
AB  - Although the increased expression of Igf-I in liver in response to GH is well
      characterized, the intracellular signaling pathways that mediate this effect have
      not been identified. Intracellular signaling molecules belonging to the Janus
      kinase-signal transducer and activator of transcription 5b (JAK2-STAT5b) pathway
      are activated by GH and have previously been shown to be required for sexually
      dimorphic body growth and the expression of liver cytochrome P450 proteins known
      to be regulated by the gender-specific temporal patterns of pituitary GH
      secretion. Here, we evaluate the role of STAT5b in GH activation of Igf-I by
      monitoring the induction of Igf-I mRNA in livers of wild-type and Stat5b(-/-)mice
      stimulated with exogenous pulses of GH. GH induced the expression of liver Igf-I
      mRNA in hypophysectomized male wild-type, but not in hypophysectomized male
      Stat5b(-/-) mice, although the Stat5b(-/-) mice exhibit both normal liver GH
      receptor expression and strong GH induction of Cytokine-inducible SH2 protein
      (Cis), which is believed to contribute to the down-regulation of GH-induced liver
      STAT5b signaling. Thus, STAT5b plays an important and specific role in liver Igf
      I gene expression.

PMID- 11517161
TI  - E2-induced degradation of uterine insulin receptor substrate-2: requirement for
      an IGF-I-stimulated, proteasome-dependent pathway.
AB  - The insulin receptor substrates are docking proteins that bind various receptor
      tyrosine kinases and signaling proteins. Previous studies have shown that E2 or
      progesterone can regulate the relative abundance of insulin receptor substrate-1
      and -2 in cells and tissues. For instance, uterine insulin receptor substrate-2
      was decreased markedly at 24 h after E2 treatment of mice. In the present study
      we used various in vivo experimental approaches to examine the mechanism by which
      E2 influences uterine insulin receptor substrate-2 expression. Uterine insulin
      receptor substrate-2 mRNA levels were diminished after E2 treatment, but this
      diminution did not account for the total reduction in insulin receptor substrate
      2 protein, suggesting that the E2-induced decrease in insulin receptor substrate
      2 is not regulated solely at the mRNA level. Cotreatment with progesterone
      prevented the E2-stimulated reduction in insulin receptor substrate-2 protein at
      24 h after hormone exposure. In addition, MG-132 and epoxomicin, inhibitors of
      proteasomal protease activity, inhibited the E2-induced decrease in uterine
      insulin receptor substrate-2 protein levels, and this correlated to an increase
      in uterine protein ubiquitination. Insulin receptor substrate-2 protein was
      diminished in uteri of E2-treated insulin receptor substrate-1-null mutant mice,
      but not in E2-treated IGF-I-null mutant mice. Furthermore, E2-induced diminution
      of uterine insulin receptor substrate-2 protein was only partially inhibited in
      the presence of wortmannin, a PI3K inhibitor. Collectively, these data suggest
      that the E2-induced decrease in uterine insulin receptor substrate-2 requires IGF
      I signaling, is not dependent solely on insulin receptor substrate-1 and PI3K,
      and is blocked by progesterone as well as by pharmacological inhibition of
      proteasomal protease activity. We speculate that the IGF-I-activated IGF-I
      receptor, in response to E2, directly or indirectly modifies insulin receptor
      substrate-2, probably through phosphorylation, leading to ubiquitination and
      subsequent degradation of this docking protein by the proteasome. This
      degradation could be a regulatory step to inhibit insulin receptor substrate-2
      dependent signaling in the uterus.

PMID- 11517162
TI  - IL-6 negatively regulates IL-11 production in vitro and in vivo.
AB  - IL-6 and IL-11 are two cytokines that increase osteoclast formation and augment
      bone resorption. PTH stimulates the production of both cytokines by human
      osteoblast-like cells. Circulating levels of IL-6 are elevated in patients with
      states of PTH excess and correlate strongly to markers of bone resorption. In
      contrast, serum levels of IL-11 were significantly reduced in patients with
      primary hyperparathyroidism compared with values in euparathyroid controls.
      Further, after successful parathyroid adenomectomy, circulating levels of IL-6
      fell, whereas IL-11 levels increased. Five-day infusions of human PTH-(1--84) in
      rodents resulted in a significant decline in mean circulating levels of IL-11,
      whereas IL-6 levels significantly increased. Pretreatment of cells and mice with
      neutralizing serum to IL-6 enhanced PTH-induced IL-11 production compared with
      the effect of pretreatment with nonimmune sera. These data indicate that IL-6
      negatively regulates IL-11 production in vivo and in vitro. Analysis of steady
      state mRNA levels in SaOS-2 cells indicated that this effect is
      posttranscriptional. As both IL-6 and IL-11 stimulate osteoclast formation, down
      regulation of IL-11 by IL-6 may help modulate the resorptive response to PTH.

PMID- 11517163
TI  - In vivo evidence for stimulation of placental, myometrial, and endometrial
      prostaglandin G/H synthase 2 by fetal cortisol replacement after fetal
      adrenalectomy.
AB  - Fetal glucocorticoid-induced premature labor in sheep is an established model of
      premature labor. However, the pathways by which fetal cortisol triggers
      subsequent maternal endocrine changes, including enhanced PG synthesis, leading
      to labor are unclear. The current study was undertaken to determine whether
      cortisol administration to adrenalectomized fetuses to clamp fetal cortisol at
      levels present early in the late gestation rise, which are inadequate to produce
      labor, can stimulate placental, myometrial, and endometrial prostaglandin G/H
      synthase 2 mRNA and protein expression. At 109--13 d gestation, fetal sheep
      adrenals were removed (n = 8), or sham surgery was performed (n = 4). From d 6
      postadrenalectomy, maternal and fetal plasma cortisol were determined daily by
      RIA. From d 7 postadrenalectomy, cortisol (4 micro/min) was continuously infused
      iv to four adrenalectomized fetuses. Endometrium, myometrium, and placentome were
      collected from all three groups of ewes (n = 4 for each group), and total RNA and
      proteins were extracted from each intrauterine tissue and analyzed by Northern
      and Western for prostaglandin G/H synthase 2 mRNA and protein. P45017 alpha
      hydroxylase mRNA was analyzed in the placentome by Northern blot. Data were
      analyzed by ANOVA. Plasma cortisol levels remained low in sham-operated and
      adrenalectomized fetus, whereas during cortisol infusion to adrenalectomized and
      cortisol-treated fetuses, plasma cortisol increased to the late gestation level.
      After adrenalectomy, prostaglandin G/H synthase 2 did not change in any tissue
      studied. Fetal plasma cortisol replacement to late gestation levels increased
      prostaglandin G/H synthase 2 to levels similar to term levels in all three
      tissues. PGHS1 mRNA and protein did not change in any group studied. There was a
      minimal increase in P45017 alpha hydroxylase mRNA in the placentome in the
      adrenalectomized and cortisol-treated group. Cortisol- induced labor further
      increased P45017 alpha hydroxylase mRNA in the placentome compared with that in
      adrenalectomized and cortisol-treated animals. These data provide evidence for in
      vivo cortisol up-regulation of prostaglandin G/H synthase 2, but not PGHS1, in
      late gestation in the ovine placentome, myometrium, and endometrium. As
      stimulation of the estrogen biosynthetic pathway was minimal in the
      adrenalectomized and cortisol-treated group, these data provide support for the
      concept that cortisol has a direct effect on prostaglandin G/H synthase 2
      expression in addition to its classical indirect pathway on prostaglandin G/H
      synthase 2 as a result of estrogen synthesis.

PMID- 11517164
TI  - Store-operated calcium influx and stimulation of steroidogenesis in rat Leydig
      cells: role of Ca(2+)-activated K(+) channels.
AB  - This study evaluates the role of internal calcium store depletion in the
      activation of ionic fluxes and steroidogenesis in adult rat Leydig cells.
      Thapsigargin and cyclopiazonic acid, two inhibitors of Ca(2+)-adenosine
      triphosphatase of internal Ca(2+) stores induced a dose-dependent rise in
      intracellular Ca(2+) concentrations following kinetics that would not be expected
      if the calcium rise was dependent only on internal calcium store depletion, but
      it was in keeping with the presence of calcium influx from the external medium.
      In fact, chelation of external calcium with EGTA during the plateau phase reduced
      the intracellular calcium concentration to basal levels. When added in calcium
      free medium, thapsigargin and cyclopiazonic acid still induced a rise in the
      intracellular calcium concentration that was transient, and when calcium was
      added back to the medium, a rapid and sustained intracellular calcium increase
      was observed. Thapsigargin and cyclopiazonic acid induced a dose-dependent rise
      in testosterone secretion in the presence and absence of calcium in the external
      medium, although in calcium-free medium this stimulatory effect was lower. Leydig
      cell plasma membrane potential monitoring demonstrated that thapsigargin and
      cyclopiazonic acid induced first a rapid hyperpolarization, followed by a
      sustained depolarization phase that was reversed by the addition of the calcium
      chelating agent EGTA. In the absence of calcium in the external medium the first
      phase of hyperpolarization was still present, but it was not followed by plasma
      membrane depolarization but by the slow return of plasma membrane potential to
      resting levels. The readdition of calcium to the external medium induced the
      rapid plasma membrane depolarization. Plasma membrane hyperpolarization was
      completely abolished by Leydig cell preincubation with the K(+) channel blockers
      tetraethylammonium and charybdotoxin. Leydig cell preincubation with K(+) channel
      inhibitors reduced the thapsigargin-stimulated Ca(2+) influx from the external
      medium and testosterone secretion. These results suggest that internal Ca(2+)
      stores depletion in rat Leydig cells induces a rise in intracellular Ca(2+),
      determining important plasma membrane potential variations that influence
      testosterone secretion.

PMID- 11517165
TI  - Control and counter-control of TGF-beta activity through FAST and Runx (CBFa)
      transcriptional elements in osteoblasts.
AB  - FAST and Runx (CBFa) transcription factors, which are expressed during specific
      phases of embryogenesis and tissue patterning, bind directly to Smad proteins and
      integrate effects induced by various TGF-beta gene family members. The DNA
      binding sequences for FAST and Runx differ only minimally. The isoform Runx2
      (previously termed CBFa1) is highly expressed by osteoblasts and regulates
      expression of the TGF-beta receptor I in these cells. Here we show that FAST
      dependent transcription is endogenously restricted in osteoblasts but can be
      significantly enhanced by disruption of Runx2 expression. Native and synthetic
      Runx2 bind to both Runx and FAST binding sequences, whereas FAST-1 efficiently
      binds only to the FAST binding sequence. However, overexpression of FAST-1
      potently suppresses TGF-beta receptor I gene expression in osteoblasts and
      thereby reduces TGF-beta activity independently of competing for Runx2 at the
      level of DNA binding. These results provide a new example of how nuclear factors
      associated with specific developmental states or tissue lineages may influence
      TGF-beta-dependent events in restricted ways.

PMID- 11517166
TI  - Peripheral administration of an angiotensin II AT(1) receptor antagonist
      decreases the hypothalamic-pituitary-adrenal response to isolation Stress.
AB  - Angiotensin II, which stimulates AT(1) receptors, is a brain and peripheral
      stress hormone. We pretreated rats with the AT(1) receptor antagonist candesartan
      for 13 d via sc-implanted osmotic minipumps, followed by 24-h isolation in
      individual metabolic cages. We measured angiotensin II receptor-type binding and
      mRNAs and tyrosine hydroxylase mRNA by quantitative autoradiography and in situ
      hybridization, catecholamines by HPLC, and hormones by RIA. Isolation increased
      AT(1) receptor binding in hypothalamic paraventricular nucleus as well as
      anterior pituitary ACTH, and decreased posterior pituitary AVP. Isolation stress
      also increased AT(1) receptor binding and AT(1B) mRNA in zona glomerulosa and
      AT(2) binding in adrenal medulla, adrenal catecholamines, tyrosine hydroxylase
      mRNA, aldosterone, and corticosterone. Candesartan blocked AT(1) binding in
      paraventricular nucleus and adrenal gland; prevented the isolation-induced
      alterations in pituitary ACTH and AVP and in adrenal corticosterone, aldosterone,
      and catecholamines; abolished the increase in AT(2) binding in adrenal medulla;
      and substantially decreased urinary AVP, corticosterone, aldosterone, and
      catecholamines during isolation. Peripheral pretreatment with an AT(1) receptor
      antagonist blocks brain and peripheral AT(1) receptors and inhibits the
      hypothalamic-pituitary-adrenal response to stress, suggesting a physiological
      role for peripheral and brain AT(1) receptors during stress and a possible
      beneficial effect of AT(1) antagonism in stress-related disorders.

PMID- 11517168
TI  - Progesterone oxidation by cytochrome P450 2D isoforms in the brain.
AB  - The existence of cytochrome P450 2D isoforms in the brain has been demonstrated,
      although their physiological functions remain to be elucidated. In this study we
      demonstrated that recombinant rat cytochrome P450 2D1 and 2D4 and human
      cytochrome P450 2D6 possess progesterone 6 beta- and 16 alpha- hydroxylation
      activities; 2 beta- and 21-hydroxylation activities; and 2 beta-, 6 beta-, 16
      alpha- and 21-hydroxylation activities, respectively. Cytochrome P450 2D4 had the
      lowest K(m) value and the highest maximum velocity value toward these activities.
      Progesterone 2 beta- and 21-hydroxylation activities were also detected in rat
      brain microsomes, and these activities were completely inhibited by
      anticytochrome P450 2D antibodies. The presence of endogenous 2 beta- and 21
      hydroxyprogesterones in rat brain tissues was also demonstrated. The mRNAs of
      cytochrome P450 2D4, CYP11A, and 3 beta-hydroxysteroid dehydrogenase were
      detected in the rat brain, suggesting that progesterone was generated from
      cholesterol by CYP11A and 3 beta-hydroxysteroid dehydrogenase and then underwent
      hydroxylation to hydroxyprogesterones by cytochrome P450 2D4 in rat brain.
      Collectively, our findings support the idea that cytochrome P450 2D may be
      involved in the regulation (metabolism and/or synthesis) of endogenous
      neuroactive steroids, such as progesterone and its derivatives, in brain tissues.

PMID- 11517167
TI  - GH regulation of IGF-I and suppressor of cytokine signaling gene expression in
      C2C12 skeletal muscle cells.
AB  - GH is required for normal postnatal growth and metabolism. GH stimulates
      postnatal growth through induction of IGF-I gene expression. Although the liver
      is the major site of GH-regulated IGF-I, recent evidence indicates that GH
      regulated IGF-I expression in nonhepatic tissues is sufficient for normal
      postnatal growth. One potentially important nonhepatic site of GH-stimulated IGF
      I expression is skeletal muscle, as injection of GH into animals leads to
      increased IGF-I mRNA in this tissue. Nevertheless, direct effects of GH in
      skeletal muscle cells in culture have not been reported. We therefore tested the
      C2C12 myogenic cell line for its response to GH and demonstrate that C2C12
      skeletal muscle cells rapidly respond to physiological levels of GH with
      increased tyrosine phosphorylation of the GH receptor, Janus kinase 2, signal
      transducer and activator of transcription-5a and -5b, insulin receptor substrate
      1, and activation of MAPKs/ERKs and protein kinase B/Akt. In these cells, GH
      stimulates the expression of IGF-I and two members of the suppressors of cytokine
      signaling family, cytokine-inducible SH2-containing protein and suppressor of
      cytokine signaling-2. Treatment of C2C12 myoblasts with either the MAPK kinase
      inhibitor PD98059 or the PI3K inhibitor wortmannin results in higher levels of GH
      induced IGF-I and suppressor of cytokine signaling-2 mRNA expression, suggesting
      that activation of MAPK and PI3K pathways has an inhibitory role in IGF-I and
      suppressor of cytokine signaling-2 gene regulation. Therefore, C2C12 cells
      provide the first in vitro model system to study various aspects of GH action in
      skeletal muscle.

PMID- 11517169
TI  - GH inhibits interferon-gamma-induced signal transducer and activator of
      transcription-1 activation and expression of the inducible isoform of nitric
      oxide synthase in INS-1 cells.
AB  - Interferon-gamma and TNFalpha synergistically induce the inducible isoform of
      nitric oxide synthase and elicit severe cytotoxicity in pancreatic beta-cells. We
      demonstrate here that GH, the well known beta-cell mitogen, inhibits nitric oxide
      production by reducing inducible nitric oxide synthase gene induction by the two
      cytokines and counteracts their cytotoxic effect in insulin-secreting INS-1
      cells. To elucidate the underlying mechanism, we examined activation of the
      transcription factors implicated in the induction of inducible nitric oxide
      synthase, signal transducer and activator of transcription-1, and nuclear factor
      kappa B. GH inhibited tyrosine phosphorylation and DNA binding of signal
      transducer and activator of transcription-1 promoted by interferon-gamma, whereas
      nuclear factor-kappa B activation by TNFalpha was not affected by GH. GH was
      found to induce suppressor of cytokine signaling-1 and -3, both of which are able
      to inhibit interferon-gamma activation of signal transducer and activator of
      transcription-1, suggesting that they are likely to mediate the inhibitory action
      of GH. Finally, exposure of INS-1 cells to interferon-gamma resulted in the
      impairment of insulin secretion in response to glucose, which was restored by the
      addition of GH. These results indicate that GH counteracts the effect of
      interferon-gamma through the inhibition of signal transducer and activator of
      transcription-1. This action of GH may be sufficient to suppress the synergistic
      induction of inducible nitric oxide synthase by interferon-gamma and TNFalpha,
      thereby preventing the cytotoxicity to beta-cells.

PMID- 11517170
TI  - Differential regulation of IGF-binding protein gene expression by cAMP in rat C6
      glioma cells.
AB  - We previously reported that cAMP inhibits autocrine IGF-I gene expression in rat
      C6 glioma cells. In this study we examined the influence of cAMP on IGF-binding
      protein gene expression in C6 cells. cAMP potently inhibited IGF-binding protein
      3 mRNA and, to a lesser extent, IGF-binding protein-4 mRNA and transiently
      stimulated IGF-binding protein-5 mRNA. The changes in secreted IGF-binding
      proteins whose molecular weights were consistent with IGF-binding protein-3 and 
      5 correlated with those of mRNA levels. cAMP decreased the IGF-binding protein-3
      mRNA half-life, but did not alter IGF-binding protein-4 and -5 mRNA half-lives.
      An IGF-binding protein-5 promoter/luciferase fusion construct containing 888 bp
      of 5'-flanking sequence and the first 114 bp of exon 1 sequence was stimulated by
      cAMP after 24 h by approximately 2-fold in transient transfection assays. 5'- or
      3'-deletion to -33 or +10 (the transcription start site was designated as +1),
      respectively, did not alter the increase caused by cAMP. Site-directed
      mutagenesis of the region from -14 to -5 led to a loss of the ability of the IGF
      binding protein-5 promoter to respond to cAMP. H89, a cell-permeable protein
      kinase A inhibitor, did not alter the regulation of IGF-binding protein mRNAs in
      response to cAMP.

PMID- 11517171
TI  - Functional segregation of the highly conserved basic motifs within the third
      endoloop of the human secretin receptor.
AB  - In this study, a mutagenesis-based strategy was employed to assess the roles of
      two highly conserved motifs (KLR and RLAR) within the third endoloop of the human
      secretin receptor. Block deletion of KLRT and mutation of Lys323 (K(323)I)
      significantly reduced cAMP accumulation, and these mutations did not affect
      ligand interaction and receptor number expressed on the cell surface. Thus, the
      KLRT region at the N terminus of the third endoloop, particularly Lys323, is
      important for G protein coupling. For the RLAR motif, receptors with
      substitutions at positions 339 and 342 from Arg to Ala (R(339, 342)A), Glu
      (R(339, 342)E), or Ile (R(339, 342)I) as well as block deletion of the RLAR motif
      were all found to be defective in both secretin-binding and cAMP production.
      Interestingly, a single mutation at the corresponding positions of Arg339 or
      Arg342 responded as the wild-type human secretin receptor in all functional
      assays, indicating that the presence of one Arg at either position within the
      RLAR motif is sufficient for a normal receptor function. Immunofluorescent
      staining of these mutant receptors showed that these Arg residues are responsible
      for surface presentation and/or receptor stability.

PMID- 11517172
TI  - Feedback regulation of PRL secretion is mediated by the transcription factor,
      signal transducer, and activator of transcription 5b.
AB  - PRL secretion from the anterior pituitary gland is inhibited by dopamine produced
      in the tuberoinfundibular dopamine neurons of the hypothalamus. The activity of
      tuberoinfundibular dopamine neurons is stimulated by PRL; thus, PRL regulates its
      own secretion by a negative feedback mechanism. PRL receptors are expressed on
      tuberoinfundibular dopamine neurons, but the intracellular signaling pathway is
      not known. We have observed that mice with a disrupted signal transducer and
      activator of transcription 5b gene have grossly elevated serum PRL
      concentrations. Despite this hyperprolactinemia, mRNA levels and immunoreactivity
      of tyrosine hydroxylase, the key enzyme in dopamine synthesis, were significantly
      lower in the tuberoinfundibular dopamine neurons of these signal transducer and
      activator of transcription 5b-deficient mice. Concentrations of the dopamine
      metabolite dihydroxyphenylacetic acid in the median eminence were also
      significantly lower in signal transducer and activator of transcription 5b
      deficient mice than in wild-type mice. No changes were observed in
      nonhypothalamic dopaminergic neuronal populations, indicating that the effects
      were selective to tuberoinfundibular dopamine neurons. These data indicate that
      in the absence of signal transducer and activator of transcription 5b, PRL signal
      transduction in tuberoinfundibular dopamine neurons is impaired, and they
      demonstrate that this transcription factor plays an obligatory and nonredundant
      role in mediating the negative feedback action of PRL on tuberoinfundibular
      dopamine neurons.

PMID- 11517173
TI  - Relaxin increases secretion of matrix metalloproteinase-2 and matrix
      metalloproteinase-9 during uterine and cervical growth and remodeling in the pig.
AB  - Matrix metalloproteinases are proteolytic enzymes that degrade the extracellular
      matrix and are essential for tissue remodeling. Uterine and cervical growth
      require remodeling of structural barriers to cell invasion and matrix
      metalloproteinase-2 and -9 degrade type IV collagen, the major component of
      basement membranes. Relaxin stimulates uterine and cervical growth and
      remodeling, which includes remodeling of support elements such as basement
      membranes. The objective of this study was to determine whether relaxin alters
      the production and/or activity of matrix metalloproteinase-2 and -9 in the uterus
      or cervix of the pig. The growth-promoting effects of relaxin were elicited by
      administering relaxin to prepubertal gilts every 6 h for 54 h. The expression of
      matrix metalloproteinase-2 and matrix metalloproteinase-9 was characterized by
      gel zymography, and proteins were quantified by immunoblotting. Total enzyme
      activity was measured using matrix metalloproteinase-specific fluorescent
      substrate assays. In both uterine and cervical tissues, immunoreactive matrix
      metalloproteinase-2 and matrix metalloproteinase-9 protein expression was similar
      in relaxin-treated and control animals. However, tissue-associated gelatinase
      activity was attenuated by relaxin (P < 0.05). In contrast, relaxin significantly
      increased the secretion of active matrix metalloproteinase-2 and -9 protein into
      uterine fluid (P < 0.05). Given the importance of matrix metalloproteinases in
      extracellular matrix degradation, the observation that relaxin promotes uterine
      secretion of matrix metalloproteinase-2 and -9 supports the concept that relaxin
      facilitates the growth and remodeling of reproductive tissues by increasing
      extracellular proteolysis in the pig reproductive tract.

PMID- 11517174
TI  - S179D-human PRL, a pseudophosphorylated human PRL analog, is an agonist and not
      an antagonist.
AB  - For many years, our group has been involved in the development of human PRL
      antagonists. In two recent publications, S179D-human PRL, a human PRL analog
      designed to mimic a putative S179-phosphorylated human PRL, was reported to be a
      highly potent antagonist of human PRL-induced proliferation and signaling in rat
      Nb2 cells. We prepared this analog with the aim of testing it in various
      bioassays involving the homologous, human PRL receptor. In our hands, S179D-
      human PRL was able to stimulate 1) the proliferation of rat Nb2 cells and of
      human mammary tumor epithelial cells (T-47D), 2) transcriptional activation of
      the lactogenic hormone response element-luciferase reporter gene, and 3)
      activation of the Janus kinase/signal transducer and activator of transcription
      and MAPK pathways. Using the previously characterized antagonist G129R-human PRL
      as a control, we failed to observe any evidence for antagonism of S179D-human PRL
      toward any of the human PRL-induced effects analyzed, including cell
      proliferation, transcriptional activation, and signaling. In conclusion, our data
      argue that S179D-human PRL is an agonist displaying slightly reduced affinity and
      activity due to local alteration of receptor binding site 1, and that the
      antagonistic properties previously attributed to S179D-human PRL cannot be
      confirmed in any of the assays analyzed in this study.

PMID- 11517175
TI  - IGF-I treatment reduces hyperphagia, obesity, and hypertension in metabolic
      disorders induced by fetal programming.
AB  - The discovery of a link between in utero experience and later metabolic and
      cardiovascular disease is one of the most important advances in epidemiology
      research of recent years. There is increasing evidence that alterations in the
      fetal environment may have long-term consequences on cardiovascular, metabolic,
      and endocrine pathophysiology in adult life. This process has been termed
      programming, and we have shown that undernutrition of the mother during gestation
      leads to programming of hyperphagia, obesity, hypertension, hyperinsulinemia, and
      hyperleptinemia in the offspring. Using this model of maternal undernutrition
      throughout pregnancy combined with postnatal hypercaloric nutrition of the
      offspring, we examined the effects of IGF-I therapy. Virgin Wistar rats (age 75
      +/- 5 d, n = 20 per group) were time mated and randomly assigned to receive food
      either ad libitum or 30% of ad libitum intake (UN) throughout pregnancy. At
      weaning, female offspring were assigned to one of two diets (control or
      hypercaloric [30% fat]). Systolic blood pressure was measured at day 175 and
      following infusion with 3 microg/g per day recombinant human IGF-1 (rh-IGF-I) by
      minipump for 14 d. Before treatment, UN offspring were hyperinsulinemic,
      hyperleptinemic, hyperphagic, obese, and hypertensive on both diets, compared
      with ad libitum offspring and this was exacerbated by hypercaloric nutrition. IGF
      I treatment increased body weight in all treated animals. However, systolic blood
      pressure, food intake, retroperitoneal and gonadal fat pad weights, and plasma
      leptin and insulin concentrations were markedly reduced with IGF-I treatment. IGF
      I treatment resulted in a 3- to 5-fold increase in 38--44 kDa and 28--30 kDa IGF
      binding proteins, although in UN animals, there was an impaired and differential
      up-regulation of these insulin-like growth factor binding proteins following IGF
      I treatment. The 24-kDa IGF binding protein representing IGF binding protein-4
      was down-regulated in all IGF-I-treated animals, but the decrease was more marked
      in UN animals. Our data suggest that IGF-I treatment alleviates hyperphagia,
      obesity, hyperinsulinemia, hyperleptinemia, and hypertension in rats programmed
      to develop the metabolic syndrome X.

PMID- 11517176
TI  - Dissociation between insulin-mediated signaling pathways and biological effects
      in placental cells: role of protein kinase B and MAPK phosphorylation.
AB  - Beyond the presence of insulin receptors, little is known of the mechanisms
      underlying the biological effects of insulin in the placenta. We show that
      phosphorylation of MAPK and protein kinase B were enhanced 286 +/- 23% and 393 +/
      17% upon insulin stimulation of JAr placental cells. MAPK activation was
      prevented by pretreatment with PD98059 but was unaffected by wortmannin. Insulin
      stimulation of protein kinase B phosphorylation was abolished by pretreatment
      with wortmannin, suggesting that it is dependent on phosphatidylinositol 3-
      kinase activation. Despite protein kinase B phosphorylation, GLUT4 translocation,
      glucose uptake, and glycogen synthesis were not stimulated by insulin. By
      contrast, glycogen synthesis was stimulated 20-fold in cells incubated with 11 mM
      glucose. Mitogenesis assessed by incorporation of [(3)H]thymidine into DNA was
      enhanced 1.9-fold in response to insulin. Stimulation of DNA synthesis was
      inhibited by pretreatment with PD98059 but was insensitive to wortmannin. These
      results indicate that stimulation of mitogenesis is one major biological effect
      of insulin in placenta cells that implicates the MAPK signaling pathway.
      Phosphatidylinositol 3-kinase- dependent protein kinase B activation is not
      sufficient to stimulate glucose transport and glycogen synthesis, highlighting
      the placenta as a nonclassic target of insulin for the regulation of glucose
      metabolism.

PMID- 11517177
TI  - LY 294002, an inhibitor of phosphatidylinositol 3-kinase, inhibits GH-mediated
      expression of the IGF-I gene in rat hepatocytes.
AB  - The signal transduction pathways that mediate GH-dependent regulation of IGF-I
      gene expression remain poorly defined. To establish a GH-responsive in vitro
      model system to study the effect of GH on the expression of the endogenous IGF-I
      gene, primary hepatocytes from adult male rats were prepared. These cells
      expressed both the GH receptor and the IGF-I gene, as demonstrated using a
      ribonuclease protection assay. Western blot analyses using antibodies directed
      against the phosphorylated forms of the ERKs, signal transducer and activator of
      transcription-5, and Akt/protein kinase B, a protein kinase that is downstream of
      PI3K, demonstrated GH-dependent phosphorylation of these signaling molecules.
      These signaling molecules are components of the major signal transduction
      pathways that are activated by GH. To determine whether GH-responsive IGF-I gene
      expression could be demonstrated in these cells, hepatocytes were treated without
      or with 50 ng/ml GH for 3--48 h. IGF-I mRNA levels increased within 3 h, and a
      maximal 2.2-fold increase was observed after 24 h of GH treatment. To determine
      whether ERK activation contributes to GH-induced IGF-I gene expression,
      hepatocytes were treated for 12 h without or with 50 ng/ml GH and 50 microM
      PD98059, an inhibitor of MAPK kinase-1 and -2. Treatment with PD98059 did not
      have a significant effect on GH-induced IGF-I gene expression. Similar studies
      were performed using 50 microM LY 294002, an inhibitor of PI3K. These studies
      demonstrated that treatment with LY 294002 completely abrogated GH-induced IGF-I
      gene expression. In contrast, PI3K-specific doses of another inhibitor of PI3K,
      wortmannin, failed to inhibit the GH-induced increase in IGF-I mRNA levels. In
      summary, rat hepatocytes in primary culture provide a good model system to study
      GH-induced IGF-I gene expression, and the results of these studies suggest that a
      signaling pathway inhibited by LY 294002, possibly a PI3K-dependent pathway, is
      important for GH-stimulated IGF-I gene expression in hepatocytes.

PMID- 11517178
TI  - Cloning and characterization of the proximal murine Phex promoter.
AB  - Phex is an endopetidase that regulates systemic phosphate homeostasis. We
      investigated Phex gene transcription by cloning and performing functional
      analysis of the 2736 bp of the 5' flanking region of the mouse Phex gene
      containing its promoter. We identified a transcription start site, a consensus
      TATA-box, and multiple potential cis-acting regulator elements. To determine
      whether the promoter directs cell-type restricted Phex expression, we transfected
      full-length and 5'-deleted Phex luciferase reporter constructs into various cell
      lines. Phex-expressing C5.18 chondrocytes displayed the highest activity of the
      transfected Phex promoter constructs compared with non-Phex-expressing COS-7
      cells, whereas promoter activity was intermediate in ROS 17/2.8 osteoblasts and
      maturation stage-dependent in MC3T3-E1 osteoblasts. Analysis of sequential 5'
      deletion mutants of the Phex promoter in ROS 17/2.8 cells revealed bimodal
      activity, suggesting that both positive and negative cis-acting regions may be
      present. The chondrogenic factor SOX9 markedly stimulated Phex promoter activity,
      whereas Cbfa1, PTH, and 1,25(OH)(2)D(3) had no effect. Our findings are
      consistent with the predominant expression of Phex in bone and cartilage.
      Additional studies will be needed to confirm the regulatory regions in the Phex
      promoter that function in a cell-restricted manner.

PMID- 11517179
TI  - Rickets in cation-sensing receptor-deficient mice: an unexpected skeletal
      phenotype.
AB  - The hypothesis that local changes in extracellular calcium may serve a
      physiological role in regulating osteoblast, osteoclast, and cartilage function
      through the extracellular cation-sensing receptor, CasR, is gaining widespread
      support, but lacks definite proof. To examine the effects of CasR deficiency on
      the skeleton, we performed a detailed analysis of the skeleton in CasR knockout
      mice (CasR(-/-)) and wild-type littermates (CasR(+/+)). CasR ablation in the
      parathyroid glands of CasR(-/-) mice resulted in hyperparathyroidism,
      hypercalcemia, and hypophosphatemia. Except for dwarfism, the expected skeletal
      manifestations of PTH excess, namely chondrodysplasia and increased mineralized
      bone formation and resorption, were not the main skeletal features in CasR(-/-)
      mice. Rather, rickets was the predominant skeletal abnormality in these animals,
      as evidenced by a widened zone of hypertrophic chondrocytes, impaired growth
      plate calcification and disorderly deposition of mineral, excessive osteoid
      accumulation, and prolonged mineralization lag time in metaphyseal bone. CasR
      transcripts were identified in cartilage and bone marrow of CasR(+/+) mice, but
      not in mineralized bone containing mature osteoblasts and osteocytes. These
      findings indicate that a calcium-sensing receptor is present in the skeleton, and
      its absence results in defective mineralization of cartilage and bone by
      mechanisms that remain to be elucidated.

PMID- 11517180
TI  - ER and PR in renomedullary interstitial cells during Syrian hamster estrogen
      induced tumorigenesis: evidence for receptor-mediated oncogenesis.
AB  - The estrogen-induced and -dependent Syrian hamster renal tumor is the most
      intensively studied model in estrogen carcinogenesis. Yet, it remains confounding
      that the kidney of this species behaves as an estrogen target tissue. As both
      reproductive and urinary systems arise from the same germinal ridge, we propose
      that some of the germinal cells, normally destined for the uterus, migrate and
      establish themselves in the renal corticomedullary region in this hamster strain.
      These ectopically located germinal cells remain dormant unless exposed to
      estrogen. Supporting this contention, a subset of renal interstitial cells,
      primarily located in the corticomedullary region, express PR after only 2 wk and
      ER alpha after 1.5--3.0 months of estrogen treatment. As treatment continues,
      groups of cells of the renal interstitium and small and large renal tumors show
      ER alpha(+) and PR(+) staining. Although ER alpha and PR isoform profiles in
      estrogen-treated hamster kidneys are distinctly different from corresponding
      uterine patterns, both receptor isoform profiles in primary renal tumors closely
      resemble those seen in hamster uteri. Renal ER alpha protein and mRNA expression
      increased after 2.0 and 4.0 months of estrogen treatment and in all renal tumors
      examined. Using nuclear image cytometry, both early small and large renal tumors
      were highly aneuploid, indicating that genomic instability is probably a critical
      early event in estrogen carcinogenesis.

PMID- 11517181
TI  - Inhibitory activity of alternative splice variants of the bullfrog GnRH receptor
      3 on wild-type receptor signaling.
AB  - Recently we characterized three distinct GnRH receptors in the bullfrog (bfGnRHR
      1, bfGnRHR-2, and bfGnRHR-3). In the present study, we further investigated the
      expression and function of splice variants, generated from the primary bfGnRHR-3
      transcript by exon skipping (splice variant 1), intron retention (splice variants
      2 and 3), and/or transcriptional slippage (splice variant 4), apart from the
      constitutively spliced form (wild-type). Cellular expression and function of the
      splice variants were examined using a transient expression system. Immunoblot
      analysis revealed that the wild-type receptor and all splice variant proteins
      were expressed in transfected HeLa cells with no significant differences in
      expression levels. These splice variants showed a very low binding affinity to
      ligand and did not induce signal transduction in response to GnRH treatment.
      Interestingly, cotransfection of the wild-type with splice variants 2--4, but not
      with splice variant 1, significantly inhibited wild-type receptor-mediated
      signaling. Subcellular localization analysis of green fluorescent protein-tagged
      wild-type and splice variant proteins revealed that the wild-type receptor
      protein was mainly localized in the cell membrane, whereas the splice variant 1
      protein was exclusively detected in the cytoplasm. The splice variant 2--4
      proteins, however, were found in both the cell membrane and cytoplasm. The
      inhibition of wild-type receptor signaling by splice variants 2--4 and the
      subcellular localization of splice variants 2-4 suggest a possible physical
      interaction of splice variants 2--4 with the wild-type receptor protein. In
      addition, the ratio of mRNA levels of the wild-type to splice variants 2--4
      significantly varied from hibernation (wild-type < splice variants 2--4) to the
      prebreeding season (wild-type > splice variants 2--4). Collectively, these
      results suggest that alternative splicing of the bfGnRHR-3 primary transcript
      plays a role in fine-tuning GnRH receptor function in amphibians.

PMID- 11517182
TI  - Differential regulation of the two principal Runx2/Cbfa1 n-terminal isoforms in
      response to bone morphogenetic protein-2 during development of the osteoblast
      phenotype.
AB  - Cbfa1/Runx2 is a transcription factor essential for bone formation and osteoblast
      differentiation. Two major N-terminal isoforms of Cbfa1, designated type I/p56
      (PEBP2aA1, starting with the sequence MRIPV) and type II/p57 (til-1, starting
      with the sequence MASNS), each regulated by distinct promoters, are known. Here,
      we show that the type I transcript is constitutively expressed in nonosseous
      mesenchymal tissues and in osteoblast progenitor cells. Cbfa1 type I isoform
      expression does not change with the differentiation status of the cells. In
      contrast, the type II transcript is increased during differentiation of primary
      osteoblasts and is induced in osteoprogenitors and in premyoblast C2C12 cells in
      response to bone morphogenetic protein-2. The functional equivalence of the two
      isoforms in activation and repression of bone-specific genes indicates
      overlapping functional roles. The presence of the ubiquitous type I isoform in
      nonosseous cells and before bone morphogenetic protein-2 induced expression of
      the type II isoform suggests a regulatory role for Cbfa1 type I in early stages
      of mesenchymal cell development, whereas type II is necessary for osteogenesis
      and maintenance of the osteoblast phenotype. Our data indicate that Cbfa1
      function is regulated by transcription, cellular protein levels, and DNA binding
      activity during osteoblast differentiation. Taken together, our studies suggest
      that developmental timing and cell type- specific expression of type I and type
      II Cbfa isoforms, and not necessarily molecular properties or sequences that
      reside in the N-terminus of Cbfa1, are the principal determinants of the
      osteogenic activity of Cbfa1.

PMID- 11517183
TI  - Ovarian granulosa cell tumors express a functional membrane receptor for anti
      Mullerian hormone in transgenic mice.
AB  - Anti-Mullerian hormone inhibits granulosa cell growth and function. Both anti
      Mullerian hormone and its type II receptor are expressed in normal granulosa
      cells. We show by histologic and molecular analyses that ovarian tumors
      developing in transgenic mice, obtained by targeted oncogenesis using an anti
      Mullerian hormone promoter-SV40 oncogene construct, are of granulosa-cell origin.
      Because tissue-specific, cell-surface molecules are of particular interest for
      the analysis and treatment of tumors, we examined the expression of anti
      Mullerian hormone type II receptor in the ovaries of these transgenic mice. We
      demonstrate that the anti-Mullerian hormone type II receptor is expressed not
      only in normal ovarian follicles, but also in granulosa cell tumors. Using a cell
      line derived from one of these tumors, we show that the anti-Mullerian hormone
      type II receptor protein is present on the surface of tumor cells and binds anti
      Mullerian hormone. Furthermore, we show that the anti-Mullerian hormone receptor
      is functional in the granulosa tumor cell line, with anti-Mullerian hormone
      treatment inducing selective activation of Smad1. In conclusion, in this study we
      present a new murine transgenic model of granulosa cell tumors of the ovary and,
      using this model, we demonstrate for the first time cell-surface expression of a
      highly tissue-specific molecule, anti-Mullerian hormone type II receptor, as well
      as the selective activation of Smad proteins by anti-Mullerian hormone, in
      granulosa tumor cells.

PMID- 11517184
TI  - Catabolic effects of continuous human PTH (1--38) in vivo is associated with
      sustained stimulation of RANKL and inhibition of osteoprotegerin and gene
      associated bone formation.
AB  - Continuous infusion of PTH in vivo results in active bone resorption. To
      investigate the molecular basis of the catabolic effect of PTH in vivo, we
      evaluated the role of OPG and RANKL, which are known to influence osteoclast
      formation and function. Weanling rats fed a calcium-free diet were
      parathyroidectomized and infused with PTH via an Alzet pump to examine: 1) the
      changes of serum-ionized calcium and osteoclast number, 2) the expression of
      OPG/RANKL mRNA and protein, and 3) the expression of osteoblast phenotype bone
      formation-associated genes such as osteoblast specific transcription factor,
      osteocalcin, bone sialoprotein, and type I collagen. PTH (1--38) (0.01--20
      microg/100 g) continuous infusion for 1--24 h resulted in a dose-dependent
      increase in serum-ionized calcium in parathyroidectomized rats and a
      corresponding dose-dependent increase in osteoclast number, indicating an
      increased bone resorption. At 20 microg/100 g PTH dose level, serum-ionized
      calcium was 2.1-fold of the vehicle control and not different from the Sham
      parathyroidectomized rats, and osteoclast number was 3-fold of the vehicle
      control and 1.7-fold of the Sham-parathyroidectomized rats. In the distal femur,
      RANKL mRNA expression was increased (27-fold) and OPG mRNA expression was
      decreased (4.6-fold). The changes in RANKL and OPG mRNA levels were rapid (as
      early as 1 h), dose dependent, and sustained over a 24-h period that was
      examined. Immunohistochemical evaluation of bone sections confirmed that OPG
      level was reduced in proximal tibial metaphysis upon PTH infusion. Circulating
      OPG protein level was also decreased by 32% when compared with the
      parathyroidectomized control. The expression of genes that mark the osteoblast
      phenotype was significantly decreased [osteoblast specific transcription factor
      (2.3-fold), osteocalcin (3-fold), bone sialoprotein (2.8-fold), and type I
      collagen (5-fold)]. These results suggest that the catabolic effect of PTH
      infusion in vivo in this well-established resorption model is associated with a
      reciprocal expression of OPG/RANKL and a co-ordinate decrease in the expression
      of bone formation-related genes. We propose that the rapid and sustained increase
      in RANKL and decrease in OPG initiate maintain and favor the cascade of events in
      the differentiation/recruitment and activation of osteoclasts.

PMID- 11517185
TI  - Evidence that TGF beta may directly modulate POMC mRNA expression in the female
      rat arcuate nucleus.
AB  - The purpose of the present study was to determine whether TGF beta, a cytokine
      secreted by hypothalamic astrocytes, was able to regulate POMC neurons in the
      arcuate nucleus. In a first set of experiments, mediobasal hypothalamic fragments
      were exposed to TGF beta(1), and the relative POMC mRNA expression was assessed
      by in situ hybridization using a radiolabeled POMC riboprobe. The results showed
      that 4 x 10(-10) M TGF beta(1) was efficient in decreasing significantly the
      amounts of POMC mRNA (P < 0.01). Interestingly, the decrease of relative POMC
      mRNA levels was higher in the rostral than in the caudal parts of the arcuate
      nucleus. In a second set of experiments, we examined the occurrence of TGF beta
      receptors expression in arcuate POMC neurons. Dual labeling in situ hybridization
      and in situ hybridization, coupled to immunohistochemical labeling, were
      performed to examine mRNA expression of the type I serine-threonine kinase
      receptor for TGF beta and the presence of type II receptor for TGF beta,
      respectively, in POMC neurons. The results indicated that TGF beta receptor I
      mRNA and TGF beta receptor II protein were expressed in numerous POMC neurons.
      Regional analysis revealed that the highest proportion of POMC neurons expressing
      TGF beta receptors was located in the rostral part of the arcuate nucleus. Using
      dual labeling immunohistochemistry, we also found that Smad2/3 immunoreactivity,
      a TGF beta(1) downstream signaling molecule, was present in the cytoplasm and
      nucleus of some POMC (beta-endorphin) neurons. We next examined whether the
      number of POMC neurons expressing TGF beta-RI mRNA was affected by sex steroids.
      Quantification of the number of POMC neurons expressing TGF beta receptor I mRNA
      in ovariectomized, ovariectomized E2-treated, and ovariectomized E2 plus
      progesterone-treated animals revealed that estrogen treatment decreased the
      expression of TGF beta receptor I mRNA in POMC neurons located in the rostral
      half of the arcuate nucleus, an effect reversed by progesterone in a subset of
      the most rostral cells. Taken together, these data reveal that TGF beta(1) may
      directly modulate the activity of POMC neurons through the activation of TGF beta
      receptors. Therefore, the present study provides additional evidence for the
      involvement of TGF beta(1) in the regulation of neuroendocrine functions and
      supports the existence of a glial-to-neurons communication within the arcuate
      nucleus.

PMID- 11517186
TI  - Increased androgen receptor expression correlates with development of age
      dependent, lobe-specific spontaneous hyperplasia of the brown Norway rat
      prostate.
AB  - Androgens are essential for development and differentiated function, as well as
      proliferation and survival of cells within the prostate gland. Age-related
      changes in the hormonal milieu, marked by a decrease in the serum androgen to
      estrogen ratio may contribute to the evolution of pathological changes, such as
      benign prostatic hyperplasia and carcinoma of the prostate gland, in older men. A
      similar phenomenon occurs in Brown Norway rats, in which the serum testosterone
      to estradiol ratio declines with age, and despite the lower serum testosterone
      level, age-dependent prostatic hyperplasia develops in the dorsal and lateral
      lobes, but not in the ventral lobe. To evaluate a role for changes in androgen
      action in the evolution of prostatic hyperplasia, we compared the immunostaining
      intensity of androgen receptor in the different prostate lobes from young (4
      months of age) and old (24 months of age) Brown Norway rats. Androgen receptor
      immunostaining was present in the nuclei of all epithelial cells and some stromal
      cells throughout the prostatic ducts of each lobe from both young and old rats.
      Whereas androgen receptor immunostaining intensity decreased in luminal
      epithelial cells of the ventral prostate from old rats, it increased in luminal
      epithelial cells of the dorsal and lateral lobes from old rats, when compared
      with young rats. To validate immunocytochemical studies, Western blot analyses
      were performed. The total tissue level of androgen receptor decreased by 30% in
      the ventral lobe of old rats, whereas tissue levels of androgen receptor
      increased 2.7-fold and 1.3-fold in the dorsal and lateral lobes, respectively, of
      old rats. Similarly, the percentage of epithelial cells staining positive for the
      proliferation marker, proliferating cell nuclear antigen, was increased
      approximately 2-fold in the dorsal and lateral lobes as a function of older age.
      The presence of higher levels of androgen receptor and increased number of
      proliferating cell nuclear antigen-positive cells in the dorsal and lateral lobes
      of old rats suggest that changes in androgen receptor levels may be related to
      the lobe-specific proliferation of cells that occurs with increasing age.
      Additional evidence for lobe-specific regulation of androgen receptor expression
      was obtained from Western blots and by immunocytochemistry following castration.
      Androgen receptor levels in the ventral and dorsal lobes, but not the lateral
      lobe, of young and old rats were down-regulated in the absence of testicular
      androgen. However, nuclear immunostaining of androgen receptor returned by 7-10 d
      after castration in the ventral and dorsal lobes in the continued absence of
      androgen. Moreover, up-regulation of the androgen receptor level occurred more
      rapidly in the ventral and dorsal lobes of old, compared with young, castrated
      rats. Taken together, these results suggest that lobe-specific and age-dependent
      differences in the regulation of androgen receptor expression might lead to
      changes in tissue androgen responsiveness and the consequent development of lobe
      specific hyperplasia in the Brown Norway rat prostate gland.

PMID- 11517187
TI  - Characterization of prohibitin in a newly established rat ovarian granulosa cell
      line.
AB  - Prohibitin is an evolutionary conserved protein that is associated with cellular
      differentiation, atresia, and luteolysis in the rat ovary. However, the specific
      cellular location and function of prohibitin in ovarian cells has not been
      clearly elucidated. To characterize the expression of prohibitin during cell
      proliferation, differentiation, and cell death, we have successfully established
      a temperature-sensitive granulosa cell line, designated RGA-1. At a permissive
      temperature of 33 C, RGA-1 cells proliferate, but revert to a differentiated
      phenotype at a nonpermissive temperature of 39 C. Significant inductions of
      prohibitin mRNA and protein expression were observed in the differentiated
      phenotype when compared with proliferating cells. Differentiated RGA-1 cells were
      found to express inhibin alpha- and beta-transcripts, as well as steroidogenic
      acute regulatory protein and peripheral-type benzodiazepine receptor proteins in
      a manner reminiscent of steroidogenic functional responses observed in primary
      differentiated granulosa cells. Prohibitin expression correlated well with the
      expression of these steroidogenic proteins. At 39 C, RGA-1 cells also displayed
      increases in p53 protein levels, indicative of growth arrest in the
      nonproliferating cells. Confocal and electron microscopic examinations revealed
      increased prohibitin localization to the mitochondria at 39 C, along with changes
      in mitochondrial size and shape. These changes were accompanied by marked
      reductions in cytochrome c oxidase subunit II levels and in unit mitochondrial
      transmembrane potential. In addition, cell fractionation studies demonstrated
      that the prohibitin protein was mainly localized to the mitochondrial membrane.
      Collectively, these findings suggest a role for prohibitin in mitochondrial
      structure and function during growth and differentiation in ovarian granulosa
      cells. Prohibitin expression may also be indicative of mitochondrial
      destabilization during apoptosis-related events.

PMID- 11517188
TI  - PRL antiapoptotic effect in the rat decidua involves the PI3K/protein kinase B
      mediated inhibition of caspase-3 activity.
AB  - During gestation, the uterus undergoes severe changes to accommodate and protect
      the developing conceptus. In particular, stromal endometrial cells proliferate
      and differentiate to form the decidual tissue, which produces PRL. Once the
      conceptus begins to grow, extensive regression by apoptosis take place in the
      decidua coincident with the loss of the PRL receptor in this tissue. In this
      report we have established for the first time that PRL, acting through the long
      form of the PRL receptor and the PI3K pathway, exerts an antiapoptotic effect in
      rat decidua. We have also shown that protein kinase B phosphorylation on serine
      473 as well as its nuclear translocation are stimulated by PRL in decidual cells.
      Moreover, we have found that caspase-3, a well known effector of apoptosis,
      becomes expressed and active in the rat decidua just at a time when this tissue
      undergoes extensive apoptosis. PRL was able to down-regulate both caspase-3 mRNA
      levels as well as activity. Furthermore, using a protein kinase B dominant
      negative expression vector, we provide evidence that PRL inhibition of caspase-3
      requires an intact protein kinase B pathway. Finally, we have also found that rat
      placental lactogen I and II dose-dependently inhibit caspase-3 mRNA, suggesting
      multiple sources of PRL in the hormonal control of rat decidual regression. In
      summary, the results of this study have defined an important role for decidual
      PRL in the normal progress of pregnancy, specifically in the regression and
      reorganization of the decidua.

PMID- 11517189
TI  - The C-terminal region of PTHrP, in addition to the nuclear localization signal,
      is essential for the intracrine stimulation of proliferation in vascular smooth
      muscle cells.
AB  - PTHrP is secreted by most cell types. In addition to a paracrine/autocrine role,
      PTHrP has "intracrine" actions, entering the nuclear compartment under the
      direction of a classic bipartite nuclear localization signal. In vascular smooth
      muscle cells, nuclear entry stimulates mitogenesis. In the current study, we
      sought to more precisely define the regions of PTHrP required for the activation
      of mitogenesis in vascular smooth muscle cells. PTHrP deletion mutants missing
      large regions [i.e. the signal peptide, N terminus (1--36), mid region (38--86),
      nuclear localization signal, C terminus (108--139), or combinations of the above]
      were expressed in A-10 vascular smooth muscle cells. The consequences on nuclear
      localization and proliferation were examined. Deletion of the nuclear
      localization signal prevented nuclear entry and slowed proliferation. Deletion of
      the highly conserved N terminus or mid region had no impact on nuclear
      localization or on proliferation. Deletion of the C terminus had no deleterious
      effect on nuclear localization but dramatically reduced proliferation. Thus, the
      nuclear localization signal is both necessary and sufficient for nuclear
      localization of PTHrP. In contrast, activation of proliferation in vascular
      smooth muscle cells requires both an intact nuclear localization signal and an
      intact C terminus. Whereas the nuclear localization signal is required for
      nuclear entry, the C terminus may serve a trans-activating function to stimulate
      mitogenesis once inside the nucleus of vascular smooth muscle cells.

PMID- 11517190
TI  - Novel intronic promoter in the rat ER alpha gene responsible for the transient
      transcription of a variant receptor.
AB  - To analyze the molecular origin of an ER variant, the truncated ER product-1,
      transiently expressed at the proestrus in lactotrope cells, we generated a 2.5-kb
      sequence of a genomic region upstream and downstream the specific sequence
      truncated ER product-1. Genomic Southern blot analysis showed that truncated ER
      product-1 is spliced from a noncoding leader exon localized within the intron 4
      of the ER alpha gene. Analysis of the promoter sequence revealed the presence of
      a major transcriptional start site, a canonical TATA box and putative cis
      regulatory elements for pituitary specific expression as well as an E-responsive
      element. In transient transfection, the truncated ER product-1 promoter was
      transcriptionally the most active in the lactotrope cell lines (MMQ). Analysis of
      truncated ER product-1 functionality showed that: 1) the protein inhibited ER
      alpha binding to the E-responsive element in electromobility shift assays, 2)
      inhibited the E2 binding to ER alpha in binding assays, 3) the truncated ER
      product-1/ER alpha complex antagonized the transcriptional activity elicited by
      E2, 4) nuclear localization of green fluorescent protein-ER alpha was altered in
      Chinese hamster ovary cell lines stably expressing truncated ER product-1.
      Collectively, these data demonstrated that the protein exerts full dominant
      negative activity against ER alpha. Moreover, truncated ER product-1/ER alpha
      complex also repressed the activity of all promoters tested to date, suggesting a
      general inhibitory effect toward transcription. In conclusion, the data suggest
      that truncated ER product-1 could regulate estrogen signaling via a specific
      promoter in lactotrope cells.

PMID- 11517192
TI  - Regulation of chondrocyte terminal differentiation in the postembryonic growth
      plate: the role of the PTHrP-Indian hedgehog axis.
AB  - Chondrocyte differentiation during embryonic bone growth is controlled by
      interactions between PTHrP and Indian hedgehog. We have now determined that the
      major components of this signaling pathway are present in the postembryonic
      growth plate. PTHrP was immunolocalized throughout the growth plate, and
      semiquantitative RT-PCR analysis of maturationally distinct chondrocyte fractions
      indicated that PTHrP, Indian hedgehog, and the PTH/PTHrP receptor were expressed
      at similar levels throughout the growth plate. However, patched, the hedgehog
      receptor, was more highly expressed in proliferating chondrocytes. Although all
      fractionated cells responded to PTHrP in culture by increasing thymidine
      incorporation and cAMP production and decreasing alkaline phosphatase activity,
      the magnitude of response was greatest in the proliferative chondrocytes. Bone
      morphogenetic proteins are considered likely intermediates in PTHrP signaling.
      Expression of bone morphogenetic protein-2 and 4--7 was detected within the
      growth plate, and PTHrP inhibited the expression of bone morphogenetic protein-4
      and 6. Although organ culture studies indicated a possible paracrine role for
      epiphyseal chondrocyte-derived PTHrP in regulating growth plate chondrocyte
      differentiation, the presence within the postembryonic growth plate of functional
      components of the PTHrP-Indian hedgehog pathway suggests that local mechanisms
      intrinsic to the growth plate exist to control the rate of endochondral
      ossification.

PMID- 11517191
TI  - ER beta inhibits proliferation and invasion of breast cancer cells.
AB  - Recent studies indicate that the expression of ER beta in breast cancer is lower
      than in the normal breast, suggesting that ER beta could play an important role
      in carcinogenesis. To investigate this hypothesis, we engineered ER-negative MDA
      MB-231 (human breast cancer cells) to reintroduce either ER alpha or ER beta
      protein with an adenoviral vector. In these cells, ER beta (as ER alpha)
      expression was monitored using RT-PCR and Western blot. ER beta protein was
      localized in the nucleus (immunocytochemistry) and able to transactivate estrogen
      responsive reporter constructs in the presence of E2. ER beta and ER alpha
      induced the expression of several endogenous genes such as pS2, TGF alpha, or the
      cyclin kinase inhibitor p21 but, in contrast to ER alpha, ER beta was unable to
      regulate c-myc proto-oncogene expression. The pure antiestrogen ICI 164, 384
      completely blocked ER alpha and ER beta estrogen-induced activities. ER beta
      inhibited MDA-MB-231 cell proliferation in a ligand-independent manner, whereas
      ER alpha inhibition of proliferation is hormone dependent. Moreover, ER beta and
      ER alpha decreased cell motility and invasion. Our data bring the first evidence
      that ER beta is an important modulator of proliferation and invasion of breast
      cancer cells and support the hypothesis that the loss of ER beta expression could
      be one of the events leading to the development of breast cancer.

PMID- 11517193
TI  - Coexpression of proprotein convertase SPC3 and the neuroendocrine precursor
      proSAAS.
AB  - The subtilisin-like proprotein convertases are a family of serine proteinases
      involved in the processing of secreted proteins via cleavage at paired basic
      residues. Until recently, only one natural inhibitor had been demonstrated, the
      neuropeptide 7B2, which contains a C-terminal domain with inhibitory activity
      against SPC2. A novel granin-like peptide precursor, named proSAAS, has recently
      been identified that contains potent and specific inhibitory activity on SPC3 in
      vitro. To exert such an inhibitory action of SPC3 activity, it would be important
      to demonstrate that proSAAS and SPC3 are colocalized. We have studied the
      expression of proSAAS and SPC3 mRNAs in the rat central nervous system and
      various peripheral tissues by in situ hybridization histochemistry. Our results
      show that, like 7B2, proSAAS is expressed with a panneuronal distribution. In the
      periphery, proSAAS is an excellent marker of endocrine cells. Double labeling
      studies show that SPC3 expression is nearly always accompanied by proSAAS
      expression. However, proSAAS was also found to be expressed in endocrine cells
      and neurons that did not express SPC3, suggesting that proSAAS could have
      additional functions other than the modulation of SPC3 activity. These data
      support the hypothesis that one of the roles of proSAAS may be to modulate the
      activity of SPC3.

PMID- 11517194
TI  - Expression of CRHR1 and CRHR2 in mouse pituitary and adrenal gland: implications
      for HPA system regulation.
AB  - Deficiency of corticotropin-releasing hormone receptor I (CRHR1) reduces anxiety
      related behavior in mice and severely impairs the stress response of the
      hypothalamic-pituitary-adrenocortical (HPA) system. Most recently, we could show
      that severe emotional stressors induce a significant rise in plasma ACTH even in
      mice deficient for the CRHR1 (Crhr1-1-) which is, however, not accompanied by an
      increase in plasma corticosterone concentration, suggesting that CRHR1 might be
      directly involved in the regulation of adrenal corticosterone release. We
      therefore used the Crhr1-1- mouse model to clarify the potential role of adrenal
      CRHR1 in the regulation of the HPA system and, in particular, of corticosterone
      secretion. In Crhr1-/- mice, intravenous ACTH administration failed to stimulate
      corticosterone secretion despite a significant upregulation of ACTH receptor mRNA
      levels in the adrenal cortex of these mutants. Further, by means of RT-PCR and in
      situ hybridization analyses, we could provide first evidence that both CRHR1 and
      CRHR2 are expressed in the mouse pituitary and adrenal cortex. Stimulation of
      pituitary CRHR2 does not induce ACTH secretion either in vitro or in vivo. Our
      data strongly suggest that CRHR1 plays a crucial role in the release of
      corticosterone from the adrenal cortex, independently of pituitary function. The
      existence of an intra-adrenal CRH/CRHR1 regulatory system which contributes to
      the corticosteroid secretory activity adds to the complexity of HPA system
      regulation and stress hormone homeostasis.

PMID- 11517195
TI  - Regulation of the ghrelin gene: growth hormone-releasing hormone upregulates
      ghrelin mRNA in the pituitary.
AB  - Ghrelin, an endogenous ligand for the growth hormone secretagogue receptor (GHS
      R), was originally purified from the rat stomach. Ghrelin specifically releases
      GH following intravenous administration, and its GH-releasing activity in vivo is
      dependent on growth hormone-releasing hormone (GHRH). We previously reported that
      the expression of the GHS-R gene in the pituitary is developmentally regulated
      and GHRH infusion increases pituitary levels of GHS-R mRNA. Ghrelin mRNA and
      peptide have recently been detected in rat and human pituitaries. However, the
      regulation of the ghrelin gene in the pituitary is unknown. In this study,
      pituitary levels of ghrelin mRNA were measured with the reverse transcriptase
      polymerase chain reaction in male rats at embryonic day (e)18 and postnatal days
      1, 10, 30, and 75. The highest concentrations of ghrelin mRNA in the pituitary
      were observed at e18 and then they declined with age. The infusion of GHRH (10
      microg/h, 4h) in freely-moving adult male rats resulted in a 1.9-fold increase in
      ghrelin mRNA levels relative to control rats (P < 0.05). These data indicated
      that the expression of the ghrelin gene in the pituitary is developmentally
      regulated and the pituitary ghrelin/GHS-R signaling system could modulate the
      regulation of GH secretion by GHRH.

PMID- 11517196
TI  - Opposite effect of prolactin and prostaglandin F(2 alpha) on the expression of
      luteal genes as revealed by rat cDNA expression array.
AB  - It is well established that prolactin (PRL) sustains, while prostaglandin F(2
      alpha) (PGF(2 alpha)) curtails, progesterone production by the rat corpus luteum
      (CL). We have previously shown that the actions of both molecules converge on the
      20 alpha-HSD gene and control its expression in a dramatically opposed manner. In
      this investigation, we have found twelve more genes that are inversely regulated
      by PRL and PGF(2 alpha). In addition to 20 alpha-HSD, PGF(2 alpha) stimulated and
      PRL inhibited PGF(2 alpha)-receptor, phospholipase C delta(1) and TGF beta(1)
      expression. In contrast PRL stimulated and PGF(2 alpha) inhibited the LH
      receptor, 11 beta-HSD2, sterol carrier protein 2, mitochondrial glutathione S
      transferase (GST), GST mu(2), inhibitory DNA-binding proteins 1, 2, and 3, and
      calcium binding protein 2. We have also identified new target genes for PRL and
      PGF(2 alpha). PGF(2 alpha) stimulated the expression of genes involved in cell
      signaling such as cell adhesion kinase-beta, ERK3, FRA2, IL-2 receptor, and 14-3
      3 proteins. PGF(2 alpha) also up-regulated the expression of the sodium channel
      beta(1), Na/K ATPase, annexin IV, GST7pi, and P450 reductase. In contrast PGF(2
      alpha) inhibited the expression of two genes involved in cell cycle: cyclin D2
      and retinoblastoma related protein (Rb2/p130). It also inhibited genes involved
      in estradiol (P-450(AROM)) and cholesterol biosynthesis (HMG-CoA synthase), as
      well as genes involved in tissue remodeling: VEGF and TIMP3. PRL had a profound
      inhibitory effect on the expression of genes encoding the ADP-ribosylation factor
      3, annexin V and c-jun, yet increased the expression of P450scc, 3beta-HSD, and
      SR-B1 (HDL-receptor), all genes involved in steroidogenesis. PRL also stimulated
      the expression of beta(2)-microglobulin, TIMP2, cytochrome c oxidase IV,
      cathepsin H and L, and copper-zinc superoxide dismutase as well as elongation
      factor SIII, heat shock protein-60 and mitochondrial ATP synthase-D. In
      conclusion, this investigation has revealed a "yin-yang" relationship between PRL
      and PGF(2 alpha) in regulating certain critical genes in the rodent CL, and has
      demonstrated novel regulation by these factors of other important genes involved
      in luteal function.

PMID- 11517197
TI  - Can we use methadone for analgesia in neonates?

PMID- 11517198
TI  - A randomised controlled trial of two methods of delivering nasal continuous
      positive airway pressure after extubation to infants weighing less than 1000 g:
      binasal (Hudson) versus single nasal prongs.
AB  - OBJECTIVES: Primary: to determine whether nasal continuous positive airway
      pressure (CPAP) delivered through binasal prongs results in a greater proportion
      of extremely low birthweight infants being successfully extubated, after a period
      of intermittent positive pressure ventilation, than nasal CPAP delivered by a
      single nasal prong. Secondary: to evaluate the effect of mode of delivery of
      nasal CPAP after extubation on the need for endotracheal reintubation, weight
      gain, rates of feeding intolerance, sepsis, suspected sepsis, cranial ultrasound
      abnormalities, retinopathy of prematurity, chronic lung disease, and the duration
      of assisted ventilation and care in the tertiary neonatal unit. DESIGN AND
      SETTING: Randomised, controlled, clinical trial conducted at the neonatal
      intensive care unit of the Royal Women's Hospital, Melbourne, Australia.
      PATIENTS: Infants of birth weight less than 1000 g, ventilated, requiring < 50%
      oxygen and ventilator rate less than or equal to 20/minute, and considered by the
      clinical management team to be ready for extubation. INTERVENTION: Infants were
      randomly allocated to receive nasal CPAP delivered through binasal (Hudson)
      prongs or a single nasal prong. PRIMARY OUTCOME MEASURE: Failure of extubation as
      defined by the following criteria: (a) apnoea (more than one episode/hour over a
      six hour period or one episode requiring bag and mask ventilation); (b) absolute
      increase in oxygen requirement greater than 15% above that required before
      extubation; (c) respiratory acidosis (pH < 7.25 with PCO(2) > 6.67 kPa). RESULTS:
      Ten of the 41 (24%) infants randomised to binasal prongs reached predetermined
      failure criteria compared with 26 of the 46 (57%) infants randomised to a single
      nasal prong (p = 0.005). Four of 17 (24%) infants of birth weight less than 800 g
      extubated to binasal prongs reached failure criteria compared with 14 of 16 (88%)
      extubated to a single nasal prong (p < 0.001). There were no significant
      differences in any of the secondary outcomes. CONCLUSIONS: For extremely low
      birthweight infants ventilated using an endotracheal tube, nasal CPAP delivered
      through binasal (Hudson) prongs is more effective in preventing failure of
      extubation than that delivered through a single nasal prong.

PMID- 11517199
TI  - A randomised control study comparing the Infant Flow Driver with nasal continuous
      positive airway pressure in preterm infants.
AB  - OBJECTIVE: To compare the effectiveness of the Infant Flow Driver (IFD) with
      single prong nasal continuous positive airway pressure (nCPAP) in preterm
      neonates affected by respiratory distress syndrome. DESIGN: Randomised controlled
      study. PATIENTS: Between September 1997 and March 1999, 36 preterm infants who
      were eligible for CPAP treatment were randomly selected for either nCPAP or IFD
      and studied prospectively for changes in oxygen requirement and/or respiratory
      rate. The requirement for mechanical ventilation, complications of treatment, and
      effects on mid-term outcome were also evaluated. RESULTS: Use of the IFD had a
      significantly beneficial effect on both oxygen requirement and respiratory rate
      (p < 0.0001) when compared with nCPAP. Moreover, O(2) requirement and respiratory
      rate were significantly decreased by four hours (p < 0.001 and p < 0.03
      respectively). The probability of remaining supplementary oxygen free over the
      first 48 hours of treatment was significantly higher in patients treated with the
      IFD than with nCPAP (p < 0.02). IFD treated patients had a higher success
      (weaning) rate (94% v 72 %) and shorter duration of treatment (49.3 (31) v 56
      (29.7) hours respectively; mean (SD)), although the difference was not
      significant. CONCLUSIONS: IFD appears to be a feasible device for managing
      respiratory distress syndrome in preterm infants, and benefits may be had with
      regard to oxygen requirement and respiratory rate when compared with nCPAP. The
      trend towards reduced requirement for mechanical ventilation, shorter clinical
      recovery time, and shorter duration of treatment requires further evaluation in a
      multicentre randomised clinical trial.

PMID- 11517200
TI  - A randomised controlled trial to compare methods of milk expression after preterm
      delivery.
AB  - OBJECTIVES: Primary: to compare sequential and simultaneous breast pumping on
      volume of milk expressed and its fat content. Secondary: to measure the effect of
      breast massage on milk volume and fat content. DESIGN: Sequential randomised
      controlled trial. SETTING: Neonatal intensive care unit, North Staffordshire
      Hospital NHS Trust. SUBJECTS: Data on 36 women were analysed; 19 women used
      simultaneous pumping and 17 used sequential pumping. INTERVENTIONS: Women were
      randomly allocated to use either simultaneous (both breasts simultaneously) or
      sequential (one breast then the other) milk expression. Stratification was used
      to ensure that the groups were balanced for parity and gestation. A crossover
      design was used for massage, with patients acting as their own controls. Women
      were randomly allocated to receive either massage or non-massage first. MAIN
      OUTCOME MEASURES: Volume of milk expressed per expression and its fat content
      (estimated by the creamatocrit method). RESULTS: Milk yield per expression was:
      sequential pumping with no massage, 51.32 g (95% confidence interval (CI) 56.57
      to 46.07); sequential pumping with massage, 78.71 g (95% CI 85.19 to 72.24);
      simultaneous pumping with no massage, 87.69 g (95% CI 96.80 to 78.57);
      simultaneous pumping with massage, 125.08 g (95% CI 140.43 to 109.74). The fat
      concentration in the milk was not affected by the increase in volume achieved by
      the interventions. CONCLUSIONS: The results are unequivocal and show that
      simultaneous pumping is more effective at producing milk than sequential pumping
      and that breast massage has an additive effect, improving milk production in both
      groups. As frequent and efficient milk removal is essential for continued
      production of milk, mothers of preterm infants wishing to express milk for their
      sick babies should be taught these techniques.

PMID- 11517201
TI  - Evaluation of the role of the neonatal nurse practitioner in resuscitation of
      preterm infants at birth.
AB  - BACKGROUND: Changes in the work patterns and numbers of medical staff in training
      grades pose a significant challenge to those responsible for the provision of an
      effective clinical neonatal service. Advanced neonatal nurse practitioners
      (ANNPs) may have a role in this changing neonatal service. The effectiveness of
      the ANNP has been established in North America but has not been properly
      evaluated in the United Kingdom. AIM: To evaluate the effectiveness of ANNPs in
      resuscitation of preterm babies at birth against the standard set by junior
      medical staff. SETTING: Regional neonatal intensive care unit. METHOD:
      Retrospective analysis of resuscitation details, other basic data, and clinical
      outcomes of 245 preterm (< 33 weeks gestation) babies born in Liverpool Women's
      Hospital between January 1998 and April 1999. RESULTS: Resuscitation teams led by
      ANNPs provided the same resuscitation interventions as those provided by
      medically led teams. Although babies resuscitated by ANNP led teams were no more
      likely to be intubated, they were intubated more quickly and received surfactant
      sooner (p = 0.0001) than babies resuscitated by medically led teams. Babies
      attended by ANNP led teams were less likely to be hypothermic on admission to the
      neonatal unit (p = 0.013). CONCLUSION: ANNPs are effective in the resuscitation
      of preterm babies at birth.

PMID- 11517202
TI  - Routine neonatal examination: effectiveness of trainee paediatrician compared
      with advanced neonatal nurse practitioner.
AB  - OBJECTIVE: To compare the effectiveness of routine neonatal examination performed
      by senior house officers (SHOs) and advanced neonatal nurse practitioners
      (ANNPs). DESIGN: A prospective study of all infants referred to specialist
      orthopaedic, ophthalmology, and cardiology clinics. A standardised proforma was
      used to record details of the professional performing the neonatal check, any
      abnormalities discovered, source of ultimate referral to the specialist clinic,
      and specialist findings. RESULTS: 527 eligible infants were recruited. For hip
      abnormalities, ANNPs displayed greater sensitivity than SHOs (96% v 74%; p <
      0.05). Similarly for eye abnormalities, ANNPs were more sensitive (100% v 33%; p
      < 0.05). There were no significant differences between ANNPs and SHOs in terms of
      positive predictive values or effectiveness of detecting cardiac abnormalities.
      There was no difference in underlying incidence of abnormalities between the two
      hospitals. CONCLUSION: ANNPs are significantly more effective in detecting
      abnormalities during the neonatal check. This has implications both for future
      workforce planning and current methods of medical training.

PMID- 11517203
TI  - Evaluation of newborn screening for medium chain acyl-CoA dehydrogenase
      deficiency in 275 000 babies.
AB  - OBJECTIVE: To evaluate newborn screening by tandem mass spectrometry for
      detection of medium chain acyl-CoA dehydrogenase (MCAD) deficiency, a fatty acid
      oxidation disorder with significant mortality in undiagnosed patients. DESIGN:
      The following were studied: (a) 13 clinically detected MCAD deficient subjects,
      most homozygous for the common A985G mutation, whose newborn screening sample was
      available; (b) 275 653 consecutive neonates undergoing routine newborn screening.
      Screened infants with blood octanoylcarnitine levels > or = 1 micromol/l were
      analysed for the A985G mutation, had analysis of plasma and repeat blood spot
      acylcarnitines and urinary organic acids, and had fibroblast fatty acid oxidation
      or acylcarnitine studies. RESULT: Twelve of the 13 patients later diagnosed
      clinically had newborn octanoylcarnitine levels > 2.3 micromol/l. Twenty three
      screened babies had initial octanoylcarnitine levels > or = 1 micromol/l. Eleven
      of 12 babies with persistent abnormalities had metabolite and/or enzyme studies
      indicating MCAD deficiency. Only four were homozygous for the A985G mutation, the
      remainder carrying one copy. CONCLUSIONS: Most patients with symptomatic MCAD
      deficiency could be detected by newborn screening. Infants actually detected had
      a lower frequency of A985G alleles than clinically diagnosed cases and may have a
      lower risk of becoming symptomatic.

PMID- 11517204
TI  - Neonatal bone marrow transplantation for severe combined immunodeficiency.
AB  - AIMS: To evaluate outcome following neonatal bone marrow transplantation (BMT)
      for severe combined immunodeficiency (SCID) when there is a family history of a
      previously affected sibling, and to compare results with those published for in
      utero BMT. METHODS: A retrospective review of cases referred and transplanted
      between 1987 and 1999, focusing on infectious and graft versus host disease
      (GvHD) complications after BMT, and T and B lymphocyte function. Thirteen
      patients received 18 stem cell transplants: four whole marrow, one cord blood, 10
      parental T cell depleted (TCD) haplo-identical, and three TCD unrelated donor
      BMT. Nine were conditioned with busulphan and cyclophosphamide. RESULTS: All are
      alive and well (six months to 11.5 years after BMT). Six had grade I-II acute
      GvHD and two chronic GvHD (now resolved). Three had a top up BMT for poor T cell
      function, one had a third BMT for graft failure and chronic GvHD, and one had a
      third BMT for graft failure. Twelve have good in vitro proliferation to T cell
      mitogens, and all have normal serum IgA levels. Three receive intravenous
      immunoglobulin; for one of these, it is less than one year since BMT. Nine are
      above the 2nd centile, and 10 of 12 old enough to be assessed have normal
      neurodevelopment. CONCLUSION: These results are better than those published for
      in utero BMT for SCID. Early postnatal BMT should be the preferred option in
      neonatal SCID.

PMID- 11517205
TI  - Outcome of very premature infants with necrotising enterocolitis cared for in
      centres with or without on site surgical facilities.
AB  - OBJECTIVE: To determine if the presence of a neonatal surgical facility on site
      has any effect on mortality and morbidity of very premature infants with
      necrotising enterocolitis (NEC). DESIGN AND SETTING: Retrospective review of
      infants of less than 29 weeks gestation cared for in the seven perinatal centres
      in New South Wales. PATIENTS: Between 1992 and 1997, 605 infants were cared for
      in two centres with in house surgical facilities (group 1) and 1195 in five
      centres where transfers were required for surgical management (group 2). RESULTS:
      Although use of antenatal steroids was significantly lower in group 1 centres
      than group 2 centres (74% v. 85% respectively), and the incidence of hyaline
      membrane disease, pneumothorax, and NEC was higher, mortality was identical
      (27%). Fifty two (9%) infants in group 1 and 72 (6%) in group 2 of comparable
      perinatal characteristics and CRIB (Clinical Risk Index for Babies) scores
      developed radiologically or pathologically proven NEC. The overall mortality of
      infants with NEC in group 1 was lower but this was not statistically significant
      (27% v. 35%). Significantly more infants with NEC in group 1 had surgery (69% v.
      39%). There were fewer postoperative deaths in group 1 and more deaths without
      surgery in group 2. The duration of respiratory and nutritional support and
      hospital stay for the survivors were similar in the two groups. In a multivariate
      analysis, shorter gestation was the only factor associated with mortality in
      infants with NEC; the presence of in house surgical facilities was not.
      CONCLUSIONS: There were no significant differences in outcome of premature
      infants with NEC managed in perinatal centres with or without on site surgical
      facilities. Early transfers should be encouraged. This finding may have
      implications for future planning of facilities for neonatal care.

PMID- 11517206
TI  - Percutaneous femoral arterial and venous catheterisation during neonatal
      intensive care.
AB  - BACKGROUND: Femoral vessel catheterisation is generally avoided in the neonatal
      period because of technical difficulties and the fear of complications. AIM: To
      review the use of femoral arterial and venous catheters inserted percutaneously
      on the neonatal intensive care unit. METHODS: Infants admitted to one of two
      regional neonatal intensive care units who underwent femoral vessel
      catheterisation were identified. Information collected included basic details,
      indication for insertion of catheter, type of catheter and insertion technique,
      duration of use, and any catheter related complications. RESULTS: Sixty five
      femoral catheters were inserted into 53 infants. The median gestational age was
      29 weeks (range 23-40). Twenty three femoral arterial catheters (FACs) were
      inserted into 21 infants and remained in situ for a median of three days (range
      one to eight). Twelve (52%) FACs remained in place until no longer required, and
      four (17%) infants developed transient ischaemia of the distal limb. Forty two
      femoral venous catheters (FVCs) were inserted into 40 infants and remained in
      situ for a median of seven days (range 1-29). Twenty seven (64%) FVCs remained in
      place until no longer required, and eight (19%) catheters were removed because of
      catheter related bloodstream infection. CONCLUSIONS: FACs and FVCs are useful
      routes of vascular access in neonates when other sites are unavailable.
      Complications from femoral vessel catheterisation include transient lower limb
      ischaemia with FACs and catheter related bloodstream infection.

PMID- 11517207
TI  - Postnatal changes in concentrations of free and bound leptin.
AB  - AIM: To evaluate the effect of maternal diabetes on the concentrations of free
      and bound leptin at birth and during postnatal adaptation. METHODS: Total, bound,
      and free leptin concentrations and the percentage of free leptin were measured in
      cord plasma and plasma at 3 days of age of 13 term infants of mothers with
      gestational diabetes mellitus (GDM) and 13 term infants of healthy mothers.
      Gestational age was 40.2 (1.4) weeks, and birth weight was 3693 (549) g (means
      (SD)). RESULTS: At birth, infants of mothers with GDM had significantly higher
      concentrations of total, bound, and free leptin and a higher percentage of free
      leptin (all p < 0.05). In all infants, these concentrations were significantly
      lower at 3 days of age than at birth (all p < 0.003), and the differences in
      concentrations of total, bound, and free leptin between the two groups were no
      longer significant. In infants of mothers with GDM, the percentage of free leptin
      remained unchanged, and was higher (p<0.05) than in infants of healthy mothers;
      in the latter group the percentage of free leptin significantly declined (p =
      0.02). CONCLUSIONS: GDM appears to influence fetoplacental leptin metabolism.
      This effect may be mediated through altered maternal glucose metabolism, or
      insulinaemia, or both.

PMID- 11517208
TI  - Non-invasive assessment of shunt and ventilation/perfusion ratio in neonates with
      pulmonary failure.
AB  - AIMS: To make non-invasive measurements of right to left (R-L) shunt and reduced
      ventilation/perfusion ratio (V(A)/Q) in neonates with pulmonary failure and to
      examine sequential changes in these variables after treatment. METHODS: Twelve
      neonates with pulmonary failure were studied. They ranged in gestational age from
      24 to 37 (median 27) weeks and were 1-39 (median 4) days old. Shunt and reduced
      V(A)/Q were derived from their effects on the relation between inspired oxygen
      pressure (PIO(2)) and arterial oxygen saturation measured with a pulse oximeter
      (SpO(2)). Pairs of PIO(2) v. SpO(2) data points were obtained by varying PIO(2)
      in a stepwise fashion. A computer algorithm based on a model of pulmonary gas
      exchange fitted a curve to these data. With PIO(2) on the abscissa, an increase
      in shunt produced a downward movement of the curve, whereas reducing V(A)/Q to <
      0.8 shifted the curve to the right. The right shift gives a variable that is
      inversely related to V(A)/Q, the PIO(2) - PO(2) difference, where PO(2) is mixed
      capillary oxygen pressure. RESULTS: Ten of the 12 infants on the first study day
      had large shunts (range 5.9-31.0%, median 19.9%, normal < 8%) and large PIO(2) -
      PO(2) differences (range 9.7-64.4 kPa, median 19.8 kPa, normal < 7 kPa)
      equivalent to a median V(A)/Q of 0.2 (normal median V(A)/Q = 0.8). Sequential
      improvement in shunt and V(A)/Q were shown in most infants after treatment.
      Sudden large changes in these variables were shown in two infants. CONCLUSION:
      This simple non-invasive method distinguishes between shunt and reduced V(A)/Q in
      neonates with pulmonary failure.

PMID- 11517209
TI  - Relations between the development of patterns of sleeping heart rate and body
      temperature in infants.
AB  - Overnight patterns of rectal temperature and heart rate were recorded from 119
      normal infants at weekly intervals from 7 to about 16 weeks of age. All data were
      collected in the infants' own homes. As previously reported, different infants
      developed an adult-like night time rectal temperature pattern abruptly at
      different ages. When heart rate data were collated by age, there was an
      apparently gradual fall in sleeping heart rate from 7 to about 14 weeks of age.
      This was, however, an artefact of data collation. Individual infants showed
      abrupt falls in heart rate at the time that the adult-like body temperature
      pattern appeared, but this occurred at different ages in different babies, so
      when data were collated cross sectionally, an apparently gradual fall resulted.
      The relation between the developmental changes in sleeping heart rate and rectal
      temperature was different in boys and girls, with girls showing a more abrupt and
      greater change in heart rate at the time of development of the adult-like body
      temperature pattern. Infants whose parents smoked had significantly lower heart
      rates once the adult-like body temperature pattern had appeared.

PMID- 11517210
TI  - Paradoxical embolism causing fatal myocardial infarction in a newborn infant.
AB  - A neonate who presented with circulatory collapse was found to have myocardial
      infarction caused by thrombotic occlusion of the left main coronary artery. At
      autopsy, a thrombus was found in the ductus venosus making paradoxical embolism
      through the foramen ovale the most likely mechanism of coronary occlusion.

PMID- 11517211
TI  - Ophthalmic Pseudomonas infection in infancy.
AB  - Four infants developed invasive Pseudomonas aeruginosa ophthalmic infections
      between 5 and 90 days of age. Three died from septicaemia, and the fourth
      required enucleation of one eye. Absent red reflexes or other eye signs in a
      septicaemic infant merit urgent ophthalmological assessment for endophthalmitis,
      in particular, Pseudomonas.

PMID- 11517212
TI  - Perinatal lessons from the past. Julius Hess, MD, (1876-1955) and the premature
      infant.

PMID- 11517213
TI  - HIP1 functions in clathrin-mediated endocytosis through binding to clathrin and
      adaptor protein 2.
AB  - Polyglutamine expansion in huntingtin is the underlying mutation leading to
      neurodegeneration in Huntington disease. This mutation influences the interaction
      of huntingtin with different proteins, including huntingtin-interacting protein 1
      (HIP1), in which affinity to bind to mutant huntingtin is profoundly reduced.
      Here we demonstrate that HIP1 colocalizes with markers of clathrin-mediated
      endocytosis in neuronal cells and is highly enriched on clathrin-coated vesicles
      (CCVs) purified from brain homogenates. HIP1 binds to the clathrin adaptor
      protein 2 (AP2) and the terminal domain of the clathrin heavy chain,
      predominantly through a small fragment encompassing amino acids 276-335. This
      region, which contains consensus clathrin- and AP2-binding sites, functions in
      conjunction with the coiled-coil domain to target HIP1 to CCVs. Expression of
      various HIP1 fragments leads to a potent block of clathrin-mediated endocytosis.
      Our findings demonstrate that HIP1 is a novel component of the endocytic
      machinery.

PMID- 11517214
TI  - Platelet-derived growth factor inhibits smooth muscle cell adhesion to
      fibronectin by ERK-dependent and ERK-independent pathways.
AB  - The adhesion of cells to the extracellular matrix plays a major role in cell
      migration. Pretreatment with platelet-derived growth factor (PDGF) inhibited the
      adhesion of smooth muscle cells to fibronectin by 80%. This inhibition decreased
      as concentrations of fibronectin increased. In the presence of 200 microm GRGDS
      peptide, only 45% of PDGF-treated cells adhered to fibronectin compared with 80%
      of control cells. This indicates that a decrease in integrin avidity was induced
      by PDGF. Cell adhesion was partially restored when the activation of the
      extracellular signal-regulated kinase (ERK) was inhibited with PD98059. The
      remaining inhibition of adhesion (50%) was independent of the fibronectin
      concentration, suggesting that the ERK pathway is involved in the decrease in
      integrin avidity. This was confirmed by depleting ERK protein levels by treatment
      with ERK antisense oligonucleotide. The adhesion of ERK control oligonucleotide
      treated cells decreased by 41% when the concentration of GRGDS peptide was
      increased from 50 to 200 microm but only decreased by 11% in ERK antisense
      oligonucleotide-treated cells. Treatment with PDGF also delayed focal complex
      assembly and inhibited stress fiber formation. Consistent with a delay in
      tyrosine phosphorylation of paxillin, PDGF treatment caused a lag in focal
      complex formation, although this was not associated with any change in Src family
      tyrosine kinase activity. Our results indicate that PDGF inhibits smooth muscle
      cells adhesion by two pathways. The first involves an ERK-dependent decrease in
      integrin avidity; the second involves the ERK-independent inhibition of focal
      complex assembly.

PMID- 11517215
TI  - Catecholamines and serotonin are differently regulated by tetrahydrobiopterin. A
      study from 6-pyruvoyltetrahydropterin synthase knockout mice.
AB  - (6R)-L-erythro-5,6,7,8-Tetrahydrobiopterin (BH4) is an essential cofactor for
      tyrosine hydroxylase (TH), tryptophan hydroxylase, phenylalanine hydroxylase, and
      nitric-oxide synthase. These enzymes synthesize neurotransmitters, e.g.
      catecholamines, serotonin, and nitric oxide (NO). We established mice unable to
      synthesize BH4 by disruption of the 6-pyruvoyltetrahydropterin synthase gene, the
      encoded protein of which catalyzes the second step of BH4 biosynthesis.
      Homozygous mice were born at the almost expected Mendelian ratio, but died within
      48 h after birth. In the brain of homozygous mutant neonates, levels of
      biopterin, catecholamines, and serotonin were extremely low. The number of TH
      molecules was highly dependent on the intracellular concentration of BH4 at nerve
      terminals. Alteration of the TH protein level by modulation of the BH4 content is
      a novel regulatory mechanism. Our data showing that catecholaminergic,
      serotonergic, and NO systems were differently affected by BH4 starvation suggest
      the possible involvement of BH4 synthesis in the etiology of monoamine-based
      neurological and neuropsychiatric disorders.

PMID- 11517216
TI  - High affinity binding of brain myosin-Va to F-actin induced by calcium in the
      presence of ATP.
AB  - Brain myosin-Va consists of two heavy chains, each containing a neck domain with
      six tandem IQ motifs that bind four to five calmodulins and one to two essential
      light chains. Previous studies demonstrated that myosin-Va exhibits an unusually
      high affinity for F-actin in the presence of ATP and that its MgATPase activity
      is stimulated by micromolar Ca(2+) in a highly cooperative manner. We demonstrate
      here that Ca(2+) also induces myosin-Va binding to and cosedimentation with F
      actin in the presence of ATP in a similar cooperative manner and calcium
      concentration range as that observed for the ATPase activity. Neither hydrolysis
      of ATP nor buildup of ADP was required for Ca(2+)-induced cosedimentation. The
      Ca(2+)-induced binding was inhibited by low temperature or by 0.6 m NaCl, but not
      by 1% Triton X-100. Tight binding between myosin-Va and pyrene-labeled F-actin in
      the presence of ATP and Ca(2+) was also detected by quenching of the pyrene
      fluorescence. Negatively stained preparations of actomyosin-Va under Ca(2+)
      induced binding conditions showed tightly packed F-actin bundles cross-linked by
      myosin-Va. Our data demonstrate that high affinity binding of myosin-Va and F
      actin in the presence of ATP or 5'-O-(thiotriphosphate) is induced by micromolar
      concentrations of Ca(2+). Since Ca(2+) regulates both the actin binding
      properties and actin-activated ATPase of myosin-Va over the same concentration
      range, we suggest that the calcium signal may regulate the mechanism of
      processivity of myosin Va.

PMID- 11517217
TI  - Chemical chaperones regulate molecular chaperones in vitro and in cells under
      combined salt and heat stresses.
AB  - Salt and heat stresses, which are often combined in nature, induce complementing
      defense mechanisms. Organisms adapt to high external salinity by accumulating
      small organic compounds known as osmolytes, which equilibrate cellular osmotic
      pressure. Osmolytes can also act as "chemical chaperones" by increasing the
      stability of native proteins and assisting refolding of unfolded polypeptides.
      Adaptation to heat stress depends on the expression of heat-shock proteins, many
      of which are molecular chaperones, that prevent protein aggregation, disassemble
      protein aggregates, and assist protein refolding. We show here that Escherichia
      coli cells preadapted to high salinity contain increased levels of glycine
      betaine that prevent protein aggregation under thermal stress. After heat shock,
      the aggregated proteins, which escaped protection, were disaggregated in salt
      adapted cells as efficiently as in low salt. Here we address the effects of four
      common osmolytes on chaperone activity in vitro. Systematic dose responses of
      glycine betaine, glycerol, proline, and trehalose revealed a regulatory effect on
      the folding activities of individual and combinations of chaperones GroEL, DnaK,
      and ClpB. With the exception of trehalose, low physiological concentrations of
      proline, glycerol, and especially glycine betaine activated the molecular
      chaperones, likely by assisting local folding in chaperone-bound polypeptides and
      stabilizing the native end product of the reaction. High osmolyte concentrations,
      especially trehalose, strongly inhibited DnaK-dependent chaperone networks, such
      as DnaK+GroEL and DnaK+ClpB, likely because high viscosity affects dynamic
      interactions between chaperones and folding substrates and stabilizes protein
      aggregates. Thus, during combined salt and heat stresses, cells can specifically
      control protein stability and chaperone-mediated disaggregation and refolding by
      modulating the intracellular levels of different osmolytes.

PMID- 11517218
TI  - Phosphorylation-dependent regulation of the interaction of amyloid precursor
      protein with Fe65 affects the production of beta-amyloid.
AB  - Neuronal Fe65 is an adapter protein that interacts with the cytoplasmic domain of
      the beta-amyloid precursor protein (APP). Although the interaction has been
      reported to occur between the second phosphotyrosine interaction domain of Fe65
      and the YENPTY motif in the cytoplasmic domain of APP, the regulatory mechanism
      and biological function of this interaction remain unknown. We report here that
      (i) a single amino acid mutation at the Thr-668 residue of APP695, located 14
      amino acids toward the amino-terminal end from the (682)YENPTY(687) motif,
      reduced the interaction between members of the Fe65 family of proteins and APP,
      whereas interaction of APP with the phosphotyrosine interaction domain of other
      APP binders such as X11-like and mammalian disabled-1 was not influenced by this
      mutation; (ii) the phosphorylation of APP at Thr-668 diminished the interaction
      of APP with Fe65 by causing a conformational change in the cytoplasmic domain
      that contains the Fe65-binding motif, YENPTY; and (iii) the expression of Fe65
      slightly suppressed maturation of APP and decreased production of beta-amyloid
      (Abeta). Mutation at Thr-668 of APP abolished the effect of Fe65 on APP
      maturation. This mutation blocked the Fe65-dependent suppression of Abeta
      production and resulted in the release of increased levels of Abeta in the
      presence of Fe65. We previously reported that during maturation of APP in
      neurons, the protein is specifically phosphorylated at Thr-668 and undergoes O
      glycosylation. The present results suggest that the phosphorylation of O
      glycosylated mature APP at Thr-668 causes a conformational change in its
      cytoplasmic domain that prevents binding of Fe65 in neurons and may lead to an
      alteration in the production of Abeta.

PMID- 11517219
TI  - Folding and stability of sweet protein single-chain monellin. An insight to
      protein engineering.
AB  - Engineered single-chain monellin (SCM) proteins were constructed by recombinant
      technology without disrupting the topology and sweet activity of native protein.
      Data from 8-anilinonaphthalene-1-sulfonic acid fluorescence, size-exclusion
      chromatography, and heteronuclear NMR strongly suggest the presence of a folding
      intermediate at 1.5 m GdnHCl for SCM protein. The structural feature of the
      folding intermediate from NMR data reveals that the secondary structures became
      mostly unstable, and protein experiences a dynamic equilibrium between native and
      unfolded state. All backbone amide protons exchange within 10 min, which imply
      that no stable hydrogen bonds exist in the secondary structural regions in the
      folding intermediate. From equilibrium unfolding and mutagenesis studies, the
      unfolding transition midpoints of mutant proteins gradually shifted toward lower
      denaturant concentration, indicating stability reductions of mutant proteins. Our
      results suggest that stability and folding pathways of SCM proteins could be
      regulated by a combined study of spectroscopy and mutagenesis, and these studies
      will provide useful information for understanding the folding kinetics of novel
      engineered proteins.

PMID- 11517220
TI  - Activities of monomeric insulin analogs at position A8 are uncorrelated with
      their thermodynamic stabilities.
AB  - Previous studies have demonstrated that the potency and thermodynamic stability
      of human insulin are enhanced in concert by substitution of Thr(A8) by arginine
      or histidine. These surface substitutions stabilize the N-terminal alpha-helix of
      the A chain, a key element of hormone-receptor recognition. Does enhanced
      stability necessarily imply enhanced activity? Here, we test by structure-based
      mutagenesis the relationship between the stability and activity of the hormone.
      To circumvent confounding effects of insulin self-association, A chain analogs
      were combined with a variant B chain (Asp(B10), Lys(B28), and Pro(B29) (DKP)) to
      create a monomeric template. Five analogs were obtained by chain combination;
      disulfide pairing proceeded in each case with native yield. CD and (1)H NMR
      spectra of the DKP analogs are essentially identical to those of DKP-insulin,
      indicating a correspondence of structures. Receptor binding affinities were
      determined by competitive displacement of (125)I-insulin from human placental
      membranes. Thermodynamic stabilities were measured by CD titration; unfolding was
      monitored as a function of guanidine concentration. In this broader collection of
      analogs receptor binding affinities are uncorrelated with stability. We suggest
      that receptor binding affinities of A8 analogs reflect local features of the
      hormone-receptor interface rather than the stability of the free hormone or the
      intrinsic C-capping propensity of the A8 side chain.

PMID- 11517221
TI  - Elevated function of blood clotting factor VIIa mutants that have enhanced
      affinity for membranes. Behavior in a diffusion-limited reaction.
AB  - Blood clotting factor VIIa is involved in the first step of the blood coagulation
      cascade, as a membrane-associated enzyme in complex with tissue factor (TF).
      Factor VIIa is also an important therapeutic agent for hemophilia where its
      function may include TF-independent as well as TF-dependent mechanisms. This
      study compared the activity of wild type factor VIIa (WT-VIIa) with that of a
      mutant with elevated affinity for membrane (P10Q/Q32E, QE-VIIa). Phospholipid and
      cell-based assays showed the mutant to have up to 40-fold higher function than WT
      VIIa in both TF-dependent and TF-independent reactions. Tissue factor-dependent
      reactions displayed the maximum enhancement when binding had reached equilibrium
      in competition with another TF-binding protein. In liposome-based assays, the
      association rate of WT-VIIa with TF occurred at a physical maximum and could not
      be improved by site-directed mutagenesis. A practical consequence was identical
      function of WT-VIIa and QE-VIIa in assays that depended entirely on assembly
      kinetics. Thus, factor VIIa mutants provided unique reagents for probing the
      mechanism of factor VIIa action. They may also offer superior agents for therapy.

PMID- 11517222
TI  - Dual regulation of mammalian myosin VI motor function.
AB  - Myosin VI is expressed in a variety of cell types and is thought to play a role
      in membrane trafficking and endocytosis, yet its motor function and regulation
      are not understood. The present study clarified mammalian myosin VI motor
      function and regulation at a molecular level. Myosin VI ATPase activity was
      highly activated by actin with K(actin) of 9 microm. A predominant amount of
      myosin VI bound to actin in the presence of ATP unlike conventional myosins.
      K(ATP) was much higher than those of other known myosins, suggesting that myosin
      VI has a weak affinity or slow binding for ATP. On the other hand, ADP markedly
      inhibited the actin-activated ATPase activity, suggesting a high affinity for
      ADP. These results suggested that myosin VI is predominantly in a strong actin
      binding state during the ATPase cycle. p21-activated kinase 3 phosphorylated
      myosin VI, and the site was identified as Thr(406). The phosphorylation of myosin
      VI significantly facilitated the actin-translocating activity of myosin VI. On
      the other hand, Ca(2+) diminished the actin-translocating activity of myosin VI
      although the actin-activated ATPase activity was not affected by Ca(2+).
      Calmodulin was not dissociated from the heavy chain at high Ca(2+), suggesting
      that a conformational change of calmodulin upon Ca(2+) binding, but not its
      physical dissociation, determines the inhibition of the motility activity. The
      present results revealed the dual regulation of myosin VI by phosphorylation and
      Ca(2+) binding to calmodulin light chain.

PMID- 11517223
TI  - The von Hippel-Lindau protein interacts with heteronuclear ribonucleoprotein a2
      and regulates its expression.
AB  - The product of the von Hippel-Lindau (VHL) tumor suppressor gene, pVHL, functions
      as a ubiquitin-protein isopeptide ligase in regulating HIF-1 protein turnover,
      thus accounting for the increased transcription of hypoxia-inducible genes that
      accompanies VHL mutations. The increased vascular endothelial growth factor mRNA
      stability in cells lacking pVHL has been hypothesized to be due to a similar
      regulation of an RNA-binding protein. We report the expression of the GLUT-1 3'
      untranslated region RNA-binding protein, heteronuclear ribonucleoprotein (hnRNP)
      A2, is specifically increased in pVHL-deficient cell lines. Enhanced hnRNP A2
      expression was apparent in all cell fractions, including polysomes, where a
      similar modest effect on hnRNP L (a GLUT-1 and VEGF 3'-untranslated region
      binding protein), was seen. Steady state levels of hnRNP A2 mRNA were unaffected.
      Regulation of hnRNP A2 levels correlated with the ability of pVHL to bind elongin
      C. Proteasome inhibition of cells expressing wild type pVHL selectively increased
      cytoplasmic hnRNP A2 levels to that seen in pVHL-deficient cells. Finally, an in
      vivo interaction between pVHL and hnRNP A2 was demonstrated in both the nucleus
      and the cytoplasm. Collectively, these data indicate that hnRNP A2 expression is
      regulated by pVHL in a manner that is dependent on elongin C interactions as well
      as functioning proteasomes.

PMID- 11517224
TI  - Functional molecular mass of a vertebrate hyaluronan synthase as determined by
      radiation inactivation analysis.
AB  - Hyaluronan (HA), a linear polysaccharide composed of N-acetylglucosamine
      glucuronic acid repeats, is found in the extracellular matrix of vertebrate
      tissues as well as the capsule of several pathogenic bacteria. The HA synthases
      (HASs) are dual-action glycosyltransferases that catalyze the addition of two
      different sugars from UDP-linked precursors to the growing HA chain. The
      prototypical vertebrate hyaluronan synthase, xlHAS1 (or DG42) from Xenopus
      laevis, is a 588-residue membrane protein. Recently, the streptococcal enzyme was
      found to function as a monomer of protein with approximately 16 lipid molecules.
      The vertebrate enzymes are larger than the streptococcal enzymes; based on the
      vertebrate HAS deduced amino acid sequence, two additional membrane-associated
      regions at the carboxyl terminus are predicted. We have utilized radiation
      inactivation to measure the target size of yeast-derived recombinant xlHAS1. The
      target size of HAS activity was confirmed using two internal standards. First,
      samples were spiked with glucose-6-phosphate dehydrogenase, an enzyme of known
      molecular weight. Second, parallel samples of native xlHAS1 and a xlHAS1-green
      fluorescent protein fusion (833 residues) were compared; substantial confidence
      was gained by using this novel internal standard. Our test also corroborated the
      basic tenets of radiation inactivation theory. We found that the vertebrate HAS
      protein functions catalytically as a monomer.

PMID- 11517225
TI  - A novel receptor-mediated regulation mechanism of type I inositol polyphosphate 5
      phosphatase by calcium/calmodulin-dependent protein kinase II phosphorylation.
AB  - D-myo-inositol 1,4,5-trisphosphate (Ins(1,4,5)P(3)) and D-myo-inositol 1,3,4,5
      tetrakisphosphate (Ins(1,3,4,5)P(4)) are both substrates of the 43-kDa type I
      inositol polyphosphate 5-phosphatase. Transient and okadaic acid-sensitive
      inhibition by 70-85% of Ins(1,4,5)P(3) and Ins(1,3,4,5)P(4) 5-phosphatase
      activities was observed in homogenates from rat cortical astrocytes, human
      astrocytoma 1321N1 cells, and rat basophilic leukemia RBL-2H3 cells after
      incubation with carbachol. The effect was reproduced in response to UTP in rat
      astrocytic cells and Chinese hamster ovary cells overexpressing human type I 5
      phosphatase. Immunodetection as well as mass spectrometric peptide mass
      fingerprinting and post-source decay (PSD) sequence data analysis after
      immunoprecipitation permitted unambiguous identification of the major native 5
      phosphatase isoform hydrolyzing Ins(1,4,5)P(3) and Ins(1,3,4,5)P(4) as type I
      inositol polyphosphate 5-phosphatase. In ortho-(32)P-preincubated cells, the
      phosphorylated 43 kDa-enzyme could be identified after receptor activation by
      immunoprecipitation followed by electrophoretic separation. Phosphorylation of
      type I 5-phosphatase was blocked after cell preincubation in the presence of
      Ca(2+)/calmodulin kinase II inhibitors (i.e. KN-93 and KN-62). In vitro
      phosphorylation of recombinant type I enzyme by Ca(2+)/calmodulin kinase II
      resulted in an inhibition (i.e. 60-80%) of 5-phosphatase activity. In this study,
      we demonstrated for the first time a novel regulation mechanism of type I 5
      phosphatase by phosphorylation in intact cells.

PMID- 11517226
TI  - Mammalian p53R2 protein forms an active ribonucleotide reductase in vitro with
      the R1 protein, which is expressed both in resting cells in response to DNA
      damage and in proliferating cells.
AB  - Recently, a homologue of the small subunit of mammalian ribonucleotide reductase
      (RNR) was discovered, called p53R2. Unlike the well characterized S phase
      specific RNR R2 protein, the new form was induced in response to DNA damage by
      the p53 protein. Because the R2 protein is specifically degraded in late mitosis
      and absent in G0/G1 cells, the induction of the p53R2 protein may explain how
      resting cells can obtain deoxyribonucleotides for DNA repair. However, no direct
      demonstration of RNR activity of the p53R2 protein was presented and furthermore,
      no corresponding RNR large subunit was identified. In this study we show that
      recombinant, highly purified human and mouse p53R2 proteins contain an iron
      tyrosyl free radical center, and both proteins form an active RNR complex with
      the human and mouse R1 proteins. UV irradiation of serum-starved, G0/G1-enriched
      mouse fibroblasts, stably transformed with an R1 promoter-luciferase reporter
      gene construct, caused a 3-fold increase in luciferase activity 24 h after
      irradiation, paralleled by an increase in the levels of R1 protein. Taken
      together, our data indicate that the R1 protein can function as the normal
      partner of the p53R2 protein and that an R1-p53R2 complex can supply resting
      cells with deoxyribonucleotides for DNA repair.

PMID- 11517227
TI  - Molecular cloning and expression of a functional snake venom vascular endothelium
      growth factor (VEGF) from the Bothrops insularis pit viper. A new member of the
      VEGF family of proteins.
AB  - During the generation of abundant expressed sequence tags from the Viperidae
      snake Bothrops insularis venom glands, we identified for the first time a cDNA
      coding for a putative vascular endothelial growth factor-like (VEGF-like)
      protein. The deduced primary sequence, after complete sequencing of the longest
      snake venom VEGF (svVEGF) cDNA, displayed similarity with vertebrate VEGFs and
      with the hypotensive factor from Vipera aspis venom. Its cDNA was subcloned,
      expressed in Escherichia coli with a His(6) tag as an insoluble monomer, and
      purified by Ni(2+)-affinity chromatography after 8 m urea extraction. Antiserum
      against svVEGF was generated and tested in Western blot against proteins from
      snake venoms and cellular extracts. The mature svVEGF appears to be ubiquitously
      distributed throughout snake venoms and was also confirmed by Northern blot
      studies of other related Viperidae species and by cDNA cloning of svVEGF from
      Bothrops jararaca pit viper. The produced recombinant protein dimerizes after
      refolding processes and was biologically characterized, showing ability to
      increase vascular permeability. These results established that svVEGF is a novel
      and important active toxin during the early stages of bothropic snake bite
      envenoming and represents a new member of the VEGF family of proteins.

PMID- 11517228
TI  - Binding of regulatory 14-3-3 proteins to the C terminus of the plant plasma
      membrane H+ -ATPpase involves part of its autoinhibitory region.
AB  - The plant plasma membrane H+ -ATPase is activated by the binding of 14-3-3
      proteins to its extreme C-terminal amino acids (YTV) and phosphorylation of the
      penultimate threonine (YpTV) is necessary for this interaction in vivo. However,
      in the presence of the fungal toxin fusicoccin (FC), binding of 14-3-3 proteins
      occurs independently of phosphorylation but still involves the YTV motif. Since
      FC exclusively binds to the complex consisting of both 14-3-3 homologs and the C
      terminal domain of the H+ -ATPase, the toxin was used as a tool to reveal
      potential protein-protein interaction sites in the enzyme's C terminus. We
      performed in vitro interaction studies by applying various C-terminal parts of
      the H+ -ATPase PMA2 from Nicotiana plumbaginifolia expressed as glutathione S
      transferase fusion peptides in E. coli. Interestingly, the PMA2 region
      encompassing residues 905-922 is implicated in FC-dependent binding of 14-3-3
      homologs. Recently, part of this region has been shown to contribute to the
      autoinhibitory action of the PMA2 C terminus. Site-directed mutagenesis of
      individual amino acids localized within this region resulted in a drastic
      decrease in FC-dependent binding of 14-3-3 proteins. Furthermore, by expressing
      the corresponding mutants of PMA2 in yeast, we observed a reduced capability of
      the mutant enzymes to functionally replace the endogenous H+ -ATPase. Notably,
      the decreased activity of the mutant enzymes was accompanied by a weakened
      binding of yeast 14-3-3 homologs to the plasma membrane of transformed cells.
      Taken together, our results suggest that a section of the autoinhibitory C
      terminal PMA2 region contributes to binding of activatory 14-3-3 proteins in the
      absence of FC.

PMID- 11517229
TI  - Reversibly bound and covalently attached ligands induce conformational changes in
      the omega loop, Cys69-Cys96, of mouse acetylcholinesterase.
AB  - We have used a combination of cysteine substitution mutagenesis and site-specific
      labeling to characterize the structural dynamics of mouse acetylcholinesterase
      (mAChE). Six cysteine-substituted sites of mAChE (Leu(76), Glu(81), Glu(84),
      Tyr(124), Ala(262), and His(287)) were labeled with the environmentally sensitive
      fluorophore, acrylodan, and the kinetics of substrate hydrolysis and inhibitor
      association were examined along with spectroscopic characteristics of the
      acrylodan-conjugated, cysteine-substituted enzymes. Residue 262, being well
      removed from the active center, appears unaffected by inhibitor binding.
      Following the binding of ligand, hypsochromic shifts in emission of acrylodan at
      residues 124 and 287, located near the perimeter of the gorge, reflect the
      exclusion of solvent and a hydrophobic environment created by the associated
      ligand. By contrast, the bathochromic shifts upon inhibitor binding seen for
      acrylodan conjugated to three omega loop (Omega loop) residues 76, 81, and 84
      reveal that the acrylodan side chains at these positions are displaced from a
      hydrophobic environment and become exposed to solvent. The magnitude of
      fluorescence emission shift is largest at position 84 and smallest at position
      76, indicating that a concerted movement of residues on the Omega loop
      accompanies gorge closure upon ligand binding. Acrylodan modification of
      substituted cysteine at position 84 reduces ligand binding and steady-state
      kinetic parameters between 1 and 2 orders of magnitude, but a similar
      substitution at position 81 only minimally alters the kinetics. Thus, combined
      kinetic and spectroscopic analyses provide strong evidence that conformational
      changes of the Omega loop accompany ligand binding.

PMID- 11517230
TI  - Determination of bradykinin B2 receptor in vivo phosphorylation sites and their
      role in receptor function.
AB  - Reversible phosphorylation plays important roles in G protein-coupled receptor
      signaling, desensitization, and endocytosis, yet the precise location and role of
      in vivo phosphorylation sites is unknown for most receptors. Using metabolic 32P
      labeling and phosphopeptide sequencing we provide a complete phosphorylation map
      of the human bradykinin B2 receptor in its native cellular environment. We
      identified three serine residues, Ser(339), Ser(346), and Ser(348), at the C
      terminal tail as principal phosphorylation sites. Constitutive phosphorylation
      occurs at Ser(348), while ligand-induced phosphorylation is found at Ser(339) and
      Ser(346)/Ser(348) that could be executed by several G protein-coupled receptor
      kinases. In addition, we found a protein kinase C-dependent phosphorylation of
      Ser(346) that was mutually exclusive with the basal phosphorylation at Ser(348)
      and therefore may be implicated in differential regulation of B2 receptor
      activation. Functional analysis of receptor mutants revealed that a low
      phosphorylation stoichiometry is sufficient to initiate receptor sequestration
      while a clustered phosphorylation around Ser(346) is necessary for
      desensitization of the B2 receptor-induced phospholipase C activation. This was
      further supported by the specifically reduced Ser(346)/Ser(348) phosphorylation
      observed upon stimulation with a nondesensitizing B2 receptor agonist. The
      differential usage of clustered phosphoacceptor sites points to distinct roles of
      multiple kinases in controlling G protein-coupled receptor function.

PMID- 11517231
TI  - Phosphorylation-dependent regulation is absent in a nonmuscle heavy meromyosin
      construct with one complete head and one head lacking the motor domain.
AB  - To understand the domain requirements of phosphorylation-dependent regulation, we
      prepared three recombinant constructs of nonmuscle heavy meromyosin IIB
      containing 1) two complete heads, 2) one complete head and one head lacking the
      motor domain, and 3) one complete head and one head lacking both motor and
      regulatory domains. Steady-state ATPase measurements showed that phosphorylation
      did not alter the affinity for actin by more than a factor of 2 for any
      construct. Phosphorylation increased V(max) by a factor of 10 for construct 1 and
      1.5-3 for construct 2 but had no effect for construct 3. Single turnover
      measurements, a better measure of slow rates inherent to unphosphorylated
      regulated myosins, showed that the single-headed construct 2, like construct 3
      retains less than 1% of the regulatory properties of the double-headed construct
      1 (300-fold activation). Therefore, a complete head cannot be down-regulated by a
      regulatory domain (without the motor domain) on the partner head. Two motor
      domains are required for regulation. This result is predicted by a structural
      model (Wendt, T., Taylor, D., Messier, T., Trybus, K. M., and Taylor, K. A.
      (1999) J. Cell Biol. 147, 1385-1390) showing interaction between the motor
      domains for unphosphorylated smooth muscle myosin, if motor-motor interaction is
      the basis for down-regulation.

PMID- 11517232
TI  - NMR structure of the "ball-and-chain" domain of KCNMB2, the beta 2-subunit of
      large conductance Ca2+- and voltage-activated potassium channels.
AB  - The auxiliary beta-subunit KCNMB2 (beta(2)) endows the non-inactivating large
      conductance Ca(2+)- and voltage-dependent potassium (BK) channel with fast
      inactivation. This process is mediated by the N terminus of KCNMB2 and closely
      resembles the "ball-and-chain"-type inactivation observed in voltage-gated
      potassium channels. Here we investigated the solution structure and function of
      the KCNMB2 N terminus (amino acids 1-45, BKbeta(2)N) using NMR spectroscopy and
      patch clamp recordings. BKbeta(2)N completely inactivated BK channels when
      applied to the cytoplasmic side; its interaction with the BK alpha-subunit is
      characterized by a particularly slow dissociation rate and an affinity in the
      upper nanomolar range. The BKbeta(2)N structure comprises two domains connected
      by a flexible linker: the pore-blocking "ball domain" (formed by residues 1-17)
      and the "chain domain" (between residues 20-45) linking it to the membrane
      segment of KCNMB2. The ball domain is made up of a flexible N terminus anchored
      at a well ordered loop-helix motif. The chain domain consists of a 4-turn helix
      with an unfolded linker at its C terminus. These structural properties explain
      the functional characteristics of BKbeta(2)N-mediated inactivation.

PMID- 11517233
TI  - Defining the structural determinants and a potential mechanism for inhibition of
      myosin phosphatase by the protein kinase C-potentiated inhibitor protein of 17
      kDa.
AB  - Contractility of smooth muscle and non-muscle microfilaments involves
      phosphorylation of myosin II light chain. Myosin light chain phosphatase (MLCP)
      is specifically inhibited by the protein kinase C-potentiated inhibitor protein
      of 17 kDa, called CPI-17, as part of Ca(2+) sensitization of vascular smooth
      muscle contraction. Phosphorylation of Thr(38) in CPI-17 enhances inhibitory
      potency toward MLCP over 1000-fold. In this study we mapped regions of CPI-17
      required for inhibition and investigated the mechanism using deletion and point
      mutants. Deletion of either the N-terminal 34 residues or C-terminal 27 residues
      gave no change in the IC(50) of either phospho- or unphospho-CPI-17. However,
      further deletion to give CPI-17 proteins of 1-102, 1-89, 1-76, and 1-67, resulted
      in much higher IC(50) values. The results indicate there is a minimal inhibitory
      domain between residues 35 and 120. A single Ala substitution at Tyr(41)
      eliminated phosphorylation-dependent inhibition, and phospho-Thr(38) in the Y41A
      protein was efficiently dephosphorylated by MLCP itself. The wild type CPI-17
      expressed in fibroblast-induced bundling and contraction of actomyosin filaments,
      whereas expression of the Y41A protein had no obvious effects. Thus, a central
      domain of CPI-17(35-120) including phospho-Thr(38) is necessary for recognition
      by myosin phosphatase and Tyr(41) arrests dephosphorylation, thereby producing
      inhibition.

PMID- 11517234
TI  - Requirement of Ras for the activation of mitogen-activated protein kinase by
      calcium influx, cAMP, and neurotrophin in hippocampal neurons.
AB  - Mitogen-activated protein (MAP) kinase plays important roles in the establishment
      of long-term potentiation both in vitro and in living animals. MAP kinase is
      activated in response to a broad range of stimuli, including calcium influx
      through NMDA receptor and L-type calcium channel, cAMP, and neurotrophins. To
      investigate the role of Ras in the activation of MAP kinase and cAMP response
      element-binding protein (CREB) in hippocampal neurons, we inhibited Ras function
      by overexpressing a Ras GTPase-activating protein, Gap1(m), or dominant negative
      Ras by means of adenovirus vectors. Gap1(m) expression almost completely
      suppressed MAP kinase activation in response to NMDA, calcium ionophore, membrane
      depolarization, forskolin, and brain-derived neurotrophic factor (BDNF). Dominant
      negative Ras also showed similar effects. On the other hand, Rap1GAP did not
      significantly inhibit the forskolin-induced activation of MAP kinase. In contrast
      to MAP kinase activation, the inactivation of Ras activity did not inhibit
      significantly NMDA-induced CREB phosphorylation, whereas BDNF-induced CREB
      phosphorylation was inhibited almost completely. These results demonstrate that
      Ras transduces signals elicited by a broad range of stimuli to MAP kinase in
      hippocampal neurons and further suggest that CREB phosphorylation depends on
      multiple pathways.

PMID- 11517235
TI  - ATP is required at an early step in compensatory endocytosis in synaptic
      terminals.
AB  - Whole-terminal capacitance measurements were used to examine membrane retrieval
      that follows Ca(2+)-triggered exocytosis in single synaptic terminals. Exocytosis
      was followed by endocytosis only when the internal solution contained a
      hydrolyzable analog of ATP. ATP-gamma-S, a poorly hydrolyzable ATP analog, did
      not support endocytosis but instead produced a rapid and profound inhibition of
      membrane retrieval. Under similar conditions, the GTP analogs GTP-gamma-S and GDP
      beta-S failed to block endocytosis, suggesting that ATP is the preferred
      substrate. Furthermore, the requirement for ATP was independent of the role of
      ATP in regulating intraterminal Ca(2+), and the role of Ca(2+) in endocytosis was
      different from that of ATP. The results suggest a direct, acute requirement for
      ATP hydrolysis in compensatory fast endocytosis in synaptic terminals. Given that
      the capacitance technique detects changes in membrane surface area, ATP must be
      required for the membrane fission step or at a step that is a prerequisite for
      membrane fission.

PMID- 11517236
TI  - Neuroprotection by Delta9-tetrahydrocannabinol, the main active compound in
      marijuana, against ouabain-induced in vivo excitotoxicity.
AB  - Excitotoxicity is a paradigm used to explain the biochemical events in both acute
      neuronal damage and in slowly progressive, neurodegenerative diseases. Here, we
      show in a longitudinal magnetic resonance imaging study that Delta(9)
      tetrahydrocannabinol (Delta(9)-THC), the main active compound in marijuana,
      reduces neuronal injury in neonatal rats injected intracerebrally with the
      Na(+)/K(+)-ATPase inhibitor ouabain to elicit excitotoxicity. In the acute phase
      Delta(9)-THC reduced the volume of cytotoxic edema by 22%. After 7 d, 36% less
      neuronal damage was observed in treated rats compared with control animals.
      Coadministration of the CB(1) cannabinoid receptor antagonist SR141716 prevented
      the neuroprotective actions of Delta(9)-THC, indicating that Delta(9)-THC
      afforded protection to neurons via the CB(1) receptor. In Delta(9)-THC-treated
      rats the volume of astrogliotic tissue was 36% smaller. The CB(1) receptor
      antagonist did not block this effect. These results provide evidence that the
      cannabinoid system can serve to protect the brain against neurodegeneration.

PMID- 11517237
TI  - Inflammatory neurodegeneration mediated by nitric oxide from activated glia
      inhibiting neuronal respiration, causing glutamate release and excitotoxicity.
AB  - Glia undergo inflammatory activation in most CNS pathologies and are capable of
      killing cocultured neurons. We investigated the mechanisms of this inflammatory
      neurodegeneration using a mixed culture of neurons, microglia, and astrocytes,
      either when the astrocytes were activated directly with lipopolysaccharide (LPS)
      and interferon-gamma (IFN-gamma) or LPS/IFN-gamma-activated microglia were added
      to mixed neuronal cultures. In either case, activated glia caused 75-100%
      necrotic cell death within 48 hr, which was completely prevented by inhibitors of
      inducible nitric oxide synthase (iNOS) (aminoguanidine or 1400W). Activated
      astrocytes or microglia produced nitric oxide (NO) (steady-state level
      approximately 0.5 microm), which immediately inhibited the cellular respiration
      of cocultured neurons, as did authentic NO. NO donors also decreased ATP levels
      and stimulated lactate production by neurons, consistent with NO-induced
      respiratory inhibition. NO donors or a specific respiratory inhibitor caused
      rapid (<1 min) release of glutamate from neuronal and neuronal-astrocytic
      cultures and subsequent neuronal death that was blocked by an antagonist of NMDA
      receptor (MK-801). MK-801 also blocked neuronal death induced by activated glia.
      High oxygen also prevented NO-induced neuronal death, consistent with death being
      induced by NO inhibition of cytochrome c oxidation in competition with oxygen.
      Thus activated glia kill neurons via NO from iNOS, which inhibits neuronal
      respiration resulting in glutamate release and subsequent excitotoxicity. This
      may contribute to neuronal cell death in inflammatory, infectious, ischemic, and
      neurodegenerative diseases.

PMID- 11517238
TI  - Dopamine-dependent synaptic plasticity in the striatal cholinergic interneurons.
AB  - The striatum, the input stage of the basal ganglia, is a critical brain structure
      for the learning of stimulus-response habits as well as motor, perceptual, and
      cognitive skills. Roles of dopamine (DA) and acetylcholine (ACh) in this form of
      implicit memory have long been considered essential, but the underlying cellular
      mechanism is still unclear. By means of patch-clamp recordings from
      corticostriatal slices of the mouse, we studied whether the identified striatal
      cholinergic interneurons undergo long-term synaptic changes after tetanic
      stimulation of cortico- and thalamostriatal fibers. Electrical stimulation of the
      fibers revealed a depolarizing and hyperpolarizing postsynaptic potential in the
      striatal cholinergic interneurons. The early depolarizing phase was considered to
      be a cortico/thalamostriatal glutamatergic EPSP, and the hyperpolarizing
      component was considered to be an intrastriatally evoked GABAergic IPSP. Tetanic
      stimulation of cortico/thalamostriatal fibers was found to induce simultaneously
      occurring long-term potentiation (LTP) of the EPSPs as well as the disynaptically
      mediated IPSPs. The induction of LTP of EPSP required a rise in intracellular
      Ca(2+) concentration and dopamine D(5), but not D(2) receptor activation. Ca(2+)
      permeable AMPA receptors might also play a part in the LTP induction. Blockade of
      NMDA receptors, metabotropic glutamate receptors, or serotonin receptors had no
      significant effects. The long-term enhancement of the disynaptic IPSPs was caused
      by a long-term increase in the occurrence rate but not the amplitude of
      disynaptically mediated IPSP in the striatal cholinergic interneurons. This dual
      mechanism of synaptic plasticity may be responsible for the long-term modulation
      of the cortico/thalamostriatal synaptic transmission.

PMID- 11517239
TI  - Serotonin receptors modulate GABA(A) receptor channels through activation of
      anchored protein kinase C in prefrontal cortical neurons.
AB  - Serotonergic neurotransmission in prefrontal cortex (PFC) has long been known to
      play a key role in regulating emotion and cognition under normal and pathological
      conditions. However, the cellular mechanisms by which this regulation occurs are
      unclear. In this study, we examined the impact of serotonin on GABA(A) receptor
      channels in PFC pyramidal neurons using combined patch-clamp recording,
      biochemical, and molecular approaches. Application of serotonin produced a
      reduction of postsynaptic GABA(A) receptor currents. Although multiple 5-HT
      receptors were coexpressed in PFC pyramidal neurons, the serotonergic modulation
      of GABA-evoked currents was mimicked by the 5-HT(2)-class agonist (-)-2,5
      dimethoxy-4-iodoamphetamine and blocked by 5-HT(2) antagonists risperidone and
      ketanserin, indicating the mediation by 5-HT(2) receptors. Inhibiting
      phospholipase C blocked the 5-HT(2) inhibition of GABA(A) currents, as did
      dialysis with protein kinase C (PKC) inhibitory peptide. Moreover, activation of
      5-HT(2) receptors in PFC slices increased the in vitro kinase activity of PKC
      toward GABA(A) receptor gamma2 subunits. Disrupting the interaction of PKC with
      its anchoring protein RACK1 (receptor for activated C kinase) eliminated the 5
      HT(2) modulation of GABA(A) currents, suggesting that RACK1-mediated targeting of
      PKC to the vicinity of GABA(A) receptors is required for the serotonergic
      signaling. Together, our results show that activation of 5-HT(2) receptors in PFC
      pyramidal neurons inhibits GABA(A) currents through phosphorylation of GABA(A)
      receptors by the activation of anchored PKC. The suppression of GABAergic
      signaling provides a novel mechanism for serotonergic modulation of PFC neuronal
      activity, which may underlie the actions of many antidepressant drugs.

PMID- 11517240
TI  - Cell swelling and a nonselective cation channel regulated by internal Ca2+ and
      ATP in native reactive astrocytes from adult rat brain.
AB  - Hypoxia-ischemia and ATP depletion are associated with glial swelling and
      blebbing, but mechanisms involved in these effects remain incompletely
      characterized. We examined morphological and electrophysiological responses of
      freshly isolated native reactive astrocytes (NRAs) after exposure to NaN(3),
      which depletes cellular ATP. Here we report that NaN(3) caused profound and
      sustained depolarization attributable to activation of a novel 35 pS Ca(2+)
      activated, [ATP](i)-sensitive nonselective cation (NC(Ca-ATP)) channel, found in
      >90% of excised membrane patches. The channel was impermeable to Cl(-), was
      nearly equally permeable to monovalent cations, with permeabilities relative to
      K(+) being P(Cs)+/P(K)+(1.06) approximately P(Na)+/P(K)+(1.04) approximately
      P(Rb)+/P(K)+(1.02) approximately P(Li)+/P(K)+(0.96), and was essentially
      impermeable to Ca(2+) and Mg(2+) (P(Ca)2+/P(K)+ approximately P(Mg)2+/P(K)+ <
      0.001), with intracellular Mg(2+) (100 microm to 1 mm) causing inward
      rectification. Pore radius, estimated by fitting relative permeabilities of
      organic cations to the Renkin equation, was 0.41 nm. This channel exhibited
      significantly different properties compared with previously reported NC(Ca-ATP)
      channels, including different sensitivity to block by various adenine nucleotides
      (EC(50) of 0.79 microm for [ATP](i), with no block by AMP or ADP), and activation
      by submicromolar [Ca](i). The apparent dissociation constant for Ca(2+) was
      voltage dependent (0.12, 0.31, and 1.5 microm at -40, -80, and -120 mV,
      respectively), with a Hill coefficient of 1.5. Channel opening by [ATP](i)
      depletion was accompanied by and appeared to precede blebbing of the cell
      membrane, suggesting participation of this channel in cation flux involved in
      cell swelling. We conclude that NRAs from adult rat brain express a 35 pS NC(Ca
      ATP) channel that may play an important role in the pathogenesis of brain
      swelling.

PMID- 11517241
TI  - ATP P2X receptor-mediated enhancement of glutamate release and evoked EPSCs in
      dorsal horn neurons of the rat spinal cord.
AB  - Presynaptic ATP P2X receptors have been proposed to play a role in modulating
      glutamate release from the first sensory synapse in the spinal cord. Using spinal
      cord slice preparations and patch-clamp recordings from dorsal horn neurons in
      lamina V of the rat spinal cord, we showed that the activation of P2X receptors
      by alpha,beta-methylene-ATP (alphabetam-ATP) resulted in a large increase in the
      frequency of spontaneous EPSCs (sEPSCs) and miniature EPSCs (mEPSCs). The
      increases in mEPSC frequency by alphabetam-ATP were not blocked by the Ca(2+)
      channel blocker, 30 microm La(3+), but were abolished in a bath solution when
      Ca(2+) was omitted. The increases in mEPSC frequency by alphabetam-ATP were
      blocked completely by the P2 receptor antagonist pyridoxalphosphate-6-azophenyl
      2',4'-disulfonic acid (PPADS) at 10 microm. Furthermore, the EPSCs evoked by
      dorsal root stimulation were potentiated by alphabetam-ATP as well as by the ecto
      ATPase inhibitor ARL67156 and were depressed in the presence of P2 receptor
      antagonists PPADS (10 microm) and suramin (5 microm). The effects of these
      compounds on the evoked EPSCs were associated with the changes in glutamate
      release probability of primary afferent central terminals. Our results indicate
      that alphabetam-ATP-sensitive P2X receptors play a significant role in modulating
      excitatory sensory synaptic transmission in the spinal cord, and the potential
      role of endogenous ATP is suggested.

PMID- 11517242
TI  - Estrogen regulates functional inhibition of hippocampal CA1 pyramidal cells in
      the adult female rat.
AB  - Previous studies have focused considerable attention on the effects of estrogen
      on excitatory synaptic input to hippocampal CA1 pyramidal cells. Estrogen
      increases the density of dendritic spines and synapses on CA1 pyramidal cells and
      increases the sensitivity of these cells to excitatory synaptic input. Little is
      known, however, about the effects of estrogen on inhibitory synaptic input to CA1
      pyramidal cells. We have used immunohistochemistry for glutamic acid
      decarboxylase and whole-cell voltage-clamp recording of IPSCs and EPSCs at
      multiple time points after estrogen treatment to (1) investigate estrogen
      regulation of synaptic inhibition in CA1 and (2) evaluate how estrogen affects
      the interaction between inhibitory and excitatory input to CA1 pyramidal cells.
      We find that estrogen transiently suppresses GABA(A)-mediated inhibition of CA1
      pyramidal cells at a time point before changes in excitatory input to these cells
      occur. This finding is consistent with the suggestion that transient
      disinhibition of CA1 pyramidal cells is involved in estrogen-induced dendritic
      spine formation. We have also found that at a later time after estrogen,
      inhibition of CA1 pyramidal cells recovers in parallel with enhancement of NMDA
      mediated excitatory input. The concurrent enhancement of GABA(A) and NMDA
      mediated input to CA1 pyramidal cells restores a balance of excitatory and
      inhibitory input to these cells and increases the potential dynamic range of CA1
      pyramidal cell responses to synaptic input.

PMID- 11517243
TI  - Myocyte enhancer factor 2A and 2D undergo phosphorylation and caspase-mediated
      degradation during apoptosis of rat cerebellar granule neurons.
AB  - Myocyte enhancer factor 2 (MEF2) proteins are important regulators of gene
      expression during the development of skeletal, cardiac, and smooth muscle. MEF2
      proteins are also present in brain and recently have been implicated in neuronal
      survival and differentiation. In this study we examined the cellular mechanisms
      regulating the activity of MEF2s during apoptosis of cultured cerebellar granule
      neurons, an established in vitro model for studying depolarization-dependent
      neuronal survival. All four MEF2 isoforms (A, B, C, and D) were detected by
      immunoblot analysis in cerebellar granule neurons. Endogenous MEF2A and MEF2D,
      but not MEF2B or MEF2C, were phosphorylated with the induction of apoptosis. The
      putative sites that were phosphorylated during apoptosis are functionally
      distinct from those previously reported to enhance MEF2 transcription. The
      increased phosphorylation of MEF2A and MEF2D was followed by decreased DNA
      binding, reduced transcriptional activity, and caspase-dependent cleavage to
      fragments containing N-terminal DNA binding domains and C-terminal
      transactivation domains. Expression of the highly homologous N terminus of MEF2A
      (1-131 amino acids) antagonized the transcriptional activity and prosurvival
      effects of a constitutively active mutant of MEF2D (MEF2D-VP16). We conclude that
      MEF2A and MEF2D are prosurvival factors with high transcriptional activity in
      postmitotic cerebellar granule neurons. When these neurons are induced to undergo
      apoptosis by lowering extracellular potassium, MEF2A and MEF2D are
      phosphorylated, followed by decreased DNA binding and cleavage by a caspase
      sensitive pathway to N-terminal fragments lacking the transactivation domains.
      The degradation of MEF2D and MEF2A and the generation of MEF2 fragments that have
      the potential to act as dominant-inactive transcription factors lead to apoptotic
      cell death.

PMID- 11517244
TI  - Modulation of excitability by alpha-dendrotoxin-sensitive potassium channels in
      neocortical pyramidal neurons.
AB  - Many neurons transduce synaptic inputs into action potentials (APs) according to
      rules that reflect their intrinsic membrane properties. Voltage-gated potassium
      channels, being numerous and diverse constituents of neuronal membrane, are
      important participants in neuronal excitability and thus in synaptic integration.
      Here we address the role of dendrotoxin-sensitive "D-type" potassium channels in
      the excitability of large pyramidal neurons in layer 5 of the rat neocortex. Low
      concentrations of 4-aminopyridine or alpha-dendrotoxin (alpha-DTX) dramatically
      increased excitability: the firing threshold for action potentials was
      hyperpolarized by 4-8 mV, and the firing frequency during a 1-sec-long 500 pA
      somatic current step was doubled. In nucleated outside-out patches pulled from
      the soma, alpha-DTX reversibly blocked a slowly inactivating potassium current
      that comprised approximately 6% of the total. This current first turned on at
      voltages just hyperpolarized to the threshold for spiking and activated steeply
      with depolarization. By assaying alpha-DTX-sensitive current in outside-out
      patches pulled from the axon and primary apical dendrite, it was found that this
      current was concentrated near the soma. We conclude that alpha-DTX-sensitive
      channels are present on large layer 5 pyramidal neurons at relatively low
      density, but their strategic location close to the site of action potential
      initiation in the axon may ensure that they have a disproportionate effect on
      neuronal excitability. Modulation of this class of channel would generate a
      powerful upregulation or downregulation of neuronal output after the integration
      of synaptic inputs.

PMID- 11517245
TI  - The C terminus of the human nicotinic alpha4beta2 receptor forms a binding site
      required for potentiation by an estrogenic steroid.
AB  - In addition to actions mediated by changes in gene expression, steroids can
      directly modulate several transmitter-gated and voltage-gated ion channels.
      Despite numerous studies showing that steroids enhance or reduce ion channel
      activity, the site(s) that mediates steroid recognition is not known. To identify
      the regions in which steroids bind and affect ion channel activity, we have taken
      advantage of the observation that human alpha4beta2 neuronal nicotinic receptors
      are potentiated by an estrogen steroid, 17beta-estradiol, whereas a rat
      alpha4beta2 receptor is not. Mutations indicate that a sequence (AGMI) at the end
      of the C terminus of the human alpha4 subunit forms a binding site required for
      17beta-estradiol potentiation. In contrast, ethynyl beta-estradiol (an oral
      contraceptive) potentiates both human and rat alpha4beta2 receptors. A single
      tryptophan in the C terminus of both the rat and the human alpha4 subunit is
      sufficient for potentiation by ethynyl beta-estradiol, probably through a pi-pi
      interaction. Mutation of this tryptophan eliminates the ability of ethynyl beta
      estradiol to potentiate rat receptors. However, in human receptors it was
      necessary to mutate both the AGMI sequence and the tryptophan to eliminate
      potentiation by ethynyl beta-estradiol. The findings that beta-estradiol requires
      the AGMI sequence but that a single C-terminal tryptophan is sufficient for
      potentiation by ethynyl beta-estradiol indicate that the C terminus forms a
      binding site for these steroids. The binding site(s) for block appears to differ
      from those involved in potentiation because the C-terminal sequence does not
      affect block by steroids such as progesterone, and progesterone does not
      competitively inhibit potentiation.

PMID- 11517246
TI  - Recruitment of the mitochondrial-dependent apoptotic pathway in amyotrophic
      lateral sclerosis.
AB  - Molecular mechanisms of apoptosis may participate in motor neuron degeneration
      produced by mutant superoxide dismutase-1 (mSOD1), the only proven cause of
      amyotrophic lateral sclerosis (ALS). Consistent with this, here we show that the
      proapoptotic protein Bax translocates from the cytosol to the mitochondria,
      whereas cytochrome c translocates from the mitochondria to the cytosol in spinal
      cords of transgenic mSOD1 mice during the progression of the disease.
      Concomitantly, caspase-9 is activated in the spinal cord of transgenic mSOD1
      mice. Only in end-stage transgenic mSOD1 mice is the downstream caspase-7
      activated and the inhibitor of apoptosis, XIAP, cleaved. These results indicate a
      sequential recruitment of molecular elements of the mitochondrial-dependent
      apoptotic pathway in transgenic mSOD1 mice. We also provide immunohistochemical
      evidence that cytochrome c translocation occurs in the spinal cord of sporadic
      ALS patients. Collectively, these data suggest that the mitochondrial-dependent
      apoptotic pathway may contribute to the demise of motor neurons in ALS and that
      targeting key molecules of this cascade may prove to be neuroprotective.

PMID- 11517247
TI  - Axonal tau mRNA localization coincides with tau protein in living neuronal cells
      and depends on axonal targeting signal.
AB  - Subcellular mRNA localization, a fundamental mechanism for regulating gene
      expression, leads to local protein translation that results in the generation of
      neuronal cell polarity. In this study, we have used P19 embryonic carcinoma
      cells, which are amenable to transfection, and selection of clonal stable cell
      lines that are not overexpressing the constructs. We identified the 3'
      untranslated region (3'UTR) tau axonal localization signal and examined its
      effect on tau protein localization in nondifferentiated and neuronally
      differentiated P19 cells. Using GFP-tagged tau constructs combined with in situ
      hybridization analysis, we demonstrated colocalization of the targeted tau mRNA
      and its translated protein in the axon and growth cone. Absence of or mutation in
      the 3'UTR axonal targeting region of tau mRNA resulted in suppression of tau mRNA
      localization, and both tau mRNA and tau protein remained in the cell body.
      Swapping between the 3'UTR tau mRNA axonal localization signal and the 3'UTR MAP2
      mRNA dendritic targeting signal proved that the localization of the proteins into
      the axon or dendrites depends on the specific 3'UTR targeting signals. Moreover,
      the identification of ribosomal proteins in the axon lends further support to the
      presence of protein synthetic machinery in the axons, a prerequisite for local
      translation. It is suggested therefore that the P19 cell system can be used to
      analyze mutations that affect mRNA transport and local translation and that it
      has the potential of being used to examine the onset of the neuronal
      differentiation process.

PMID- 11517248
TI  - Chronic blockade of glutamate receptors enhances presynaptic release and
      downregulates the interaction between synaptophysin-synaptobrevin-vesicle
      associated membrane protein 2.
AB  - During development of neuronal circuits, presynaptic and postsynaptic functions
      are adjusted in concert, to optimize interneuronal signaling. We have
      investigated whether activation of glutamate receptors affects presynaptic
      function during synapse formation, when constitutive synaptic vesicle recycling
      is downregulated. Using primary cultures of hippocampal neurons as a model
      system, we have found that chronic exposure to both NMDA and non-NMDA glutamate
      receptor blockers during synaptogenesis produces an increase in miniature EPSC
      (mEPSC) frequency, with no significant changes in mEPSC amplitude or in the
      number of synapses. Enhanced synaptic vesicle recycling, selectively in
      glutamatergic nerve terminals, was confirmed by the increased uptake of
      antibodies directed against the lumenal domain of synaptotagmin. No increased
      uptake was detected in neuronal cultures grown in the chronic presence of TTX,
      speaking against an indirect effect caused by decreased electrical activity.
      Enhanced mEPSC frequency correlated with a reduction of synaptophysin
      synaptobrevin-vesicle-associated membrane protein 2 (VAMP2) complexes detectable
      by immunoprecipitation. Intracellular perfusion with a peptide that inhibits the
      binding of synaptophysin to synaptobrevin-VAMP2 induced a remarkable increase of
      mEPSC frequency in control but not in glutamate receptor blocker-treated neurons.
      These findings suggest that activation of glutamate receptors plays a role in the
      downregulation of the basal rate of synaptic vesicle recycling that accompanies
      synapse formation. They also suggest that one of the mechanisms through which
      this downregulation is achieved is an increased interaction of synaptophysin with
      synaptobrevin-VAMP2.

PMID- 11517249
TI  - c-Jun N-terminal kinase (JNK)-interacting protein-1b/islet-brain-1 scaffolds
      Alzheimer's amyloid precursor protein with JNK.
AB  - Using a yeast two-hybrid method, we searched for amyloid precursor protein (APP)
      interacting molecules by screening mouse and human brain libraries. In addition
      to known interacting proteins containing a phosphotyrosine-interaction-domain
      (PID)-Fe65, Fe65L, Fe65L2, X11, and mDab1, we identified, as a novel APP
      interacting molecule, a PID-containing isoform of mouse JNK-interacting protein-1
      (JIP-1b) and its human homolog IB1, the established scaffold proteins for JNK.
      The APP amino acids Tyr(682), Asn(684), and Tyr(687) in the G(681)YENPTY(687)
      region were all essential for APP/JIP-1b interaction, but neither Tyr(653) nor
      Thr(668) was necessary. APP-interacting ability was specific for this additional
      isoform containing PID and was shared by both human and mouse homologs. JIP-1b
      expressed by mammalian cells was efficiently precipitated by the cytoplasmic
      domain of APP in the extreme Gly(681)-Asn(695) domain-dependent manner.
      Reciprocally, both full-length wild-type and familial Alzheimer's disease mutant
      APPs were precipitated by PID-containing JIP constructs. Antibodies raised
      against the N and C termini of JIP-1b coprecipitated JIP-1b and wild-type or
      mutant APP in non-neuronal and neuronal cells. Moreover, human JNK1beta1 formed a
      complex with APP in a JIP-1b-dependent manner. Confocal microscopic examination
      demonstrated that APP and JIP-1b share similar subcellular localization in
      transfected cells. These data indicate that JIP-1b/IB1 scaffolds APP with JNK,
      providing a novel insight into the role of the JNK scaffold protein as an
      interface of APP with intracellular functional molecules.

PMID- 11517250
TI  - The mitochondrial permeability transition pore and nitric oxide synthase mediate
      early mitochondrial depolarization in astrocytes during oxygen-glucose
      deprivation.
AB  - Recent studies suggest that the degree of mitochondrial dysfunction in cerebral
      ischemia may be an important determinant of the final extent of tissue injury.
      Although loss of mitochondrial membrane potential (psi(m)), one index of
      mitochondrial dysfunction, has been documented in neurons exposed to ischemic
      conditions, it is not yet known whether astrocytes, which are relatively
      resistant to ischemic injury, experience changes in psi(m) under similar
      conditions. To address this, we exposed cortical astrocytes cultured alone or
      with neurons to oxygen-glucose deprivation (OGD) and monitored psi(m) using
      tetramethylrhodamine ethyl ester. Both neurons and astrocytes exhibited profound
      loss of psi(m) after 45-60 min of OGD. However, although this exposure is lethal
      to nearly all neurons, it is hours less than that needed to kill astrocytes.
      Astrocyte psi(m) was rescued during OGD by cyclosporin A, a permeability
      transition pore blocker, and (G)N-nitro-arginine, a nitric oxide synthase
      inhibitor. Loss of mitochondrial membrane potential in astrocytes was not
      accompanied by depolarization of the plasma membrane. Recovery of astrocyte
      psi(m) after reintroduction of O(2) and glucose occurred over a surprisingly long
      period (>1 hr), suggesting that OGD caused specific, reversible changes in
      astrocyte mitochondrial physiology beyond the simple lack of O(2) and glucose.
      Decreased psi(m) was associated with a cyclosporin A-sensitive loss of cytochrome
      c but not with activation of caspase-3 or caspase-9. Our data suggest that
      astrocyte mitochondrial depolarization could be a previously unrecognized event
      early in ischemia and that strategies that target the mitochondrial component of
      ischemic injury may benefit astrocytes as well as neurons.

PMID- 11517251
TI  - Tumor necrosis factor receptor deletion reduces nuclear factor-kappaB activation,
      cellular inhibitor of apoptosis protein 2 expression, and functional recovery
      after traumatic spinal cord injury.
AB  - Tumor necrosis factor-alpha (TNF-alpha) expression has been documented
      extensively in animal models of traumatic spinal cord injury (SCI). However, the
      pathophysiological significance of TNF-alpha expression in the injured cord
      remains to be delineated. The TNF receptor (TNFR)-nuclear factor-kappaB (NF
      kappaB) signal transduction pathway is important for maintaining cell viability.
      NF-kappaB exerts anti-apoptotic effects via an endogenous caspase inhibitory
      system mediated by cellular inhibitor of apoptosis protein 2 (c-IAP2). NF-kappaB
      transactivates c-IAP2 to inhibit caspase-3 activation. Progressive cell death,
      including morphological and biochemical features suggestive of apoptosis, has
      been noted after SCI. We explored the effects of TNFR1 or TNFR2 deletion on the
      apoptotic events downstream of NF-kappaB in relation to SCI pathology and
      functional recovery. Nuclear proteins from the injured cords of the TNFR1(-/-)
      mice had a reduced NF-kappaB binding activity compared with the wild-type
      controls. This decrease in NF-kappaB activation was accompanied by a reduction in
      c-IAP2 expression and an increase in the active form of caspase-3 protein. After
      SCI the TNFR1(-/-) mice had greater numbers of apoptotic cells, a larger lesion
      size, and worse functional recovery than wild-type mice. TNFR2-deficient mice had
      a similar, although not as pronounced, consequence as the TNFR1(-/-) mice. These
      findings support the argument that the TNFR-NF-kappaB pathway is beneficial for
      limiting apoptotic cell death after SCI and that a defective TNFR-NF-kappaB
      pathway results in a poorer neurological outcome. A worse functional outcome in
      TNFR(-/-) mice suggests that an endogenous apoptosis inhibitory mechanism
      mediated by TNFR activation, NF-kappaB, and c-IAP2 may be of pathophysiological
      importance.

PMID- 11517252
TI  - Hippocampal heterotopia lack functional Kv4.2 potassium channels in the
      methylazoxymethanol model of cortical malformations and epilepsy.
AB  - Human cortical malformations often result in severe forms of epilepsy. Although
      the morphological properties of cells within these malformations are well
      characterized, very little is known about the function of these cells. In rats,
      prenatal methylazoxymethanol (MAM) exposure produces distinct nodules of
      disorganized pyramidal-like neurons (e.g., nodular heterotopia) and loss of
      lamination in cortical and hippocampal structures. Hippocampal nodular
      heterotopias are prone to hyperexcitability and may contribute to the increased
      seizure susceptibility observed in these animals. Here we demonstrate that
      heterotopic pyramidal neurons in the hippocampus fail to express a potassium
      channel subunit corresponding to the fast, transient A-type current. In situ
      hybridization and immunohistochemical analysis revealed markedly reduced
      expression of Kv4.2 (A-type) channel subunits in heterotopic cell regions of the
      hippocampus of MAM-exposed rats. Patch-clamp recordings from visualized
      heterotopic neurons indicated a lack of fast, transient (I(A))-type potassium
      current and hyperexcitable firing. A-type currents were observed on normotopic
      pyramidal neurons in MAM-exposed rats and on interneurons, CA1 pyramidal neurons,
      and cortical layer V-VI pyramidal neurons in saline-treated control rats. Changes
      in A-current were not associated with an alteration in the function or expression
      of delayed, rectifier (Kv2.1) potassium channels on heterotopic cells. We
      conclude that heterotopic neurons lack functional A-type Kv4.2 potassium channels
      and that this abnormality could contribute to the increased excitability and
      decreased seizure thresholds associated with brain malformations in MAM-exposed
      rats.

PMID- 11517253
TI  - Calmodulin kinase pathway mediates the K+-induced increase in Gap junctional
      communication between mouse spinal cord astrocytes.
AB  - Astrocytes are coupled to one another by gap junction channels that allow the
      diffusion of ions and small molecules throughout the interconnected syncytium. In
      astrocytes, gap junctions are believed to participate in spatial buffering
      removing the focal excess of potassium resultant from intense neuronal activity
      by current loops through the syncytium and are also implicated in the propagation
      of astrocytic calcium waves, a form of extraneuronal signaling. Gap junctions can
      be modulated by several factors, including elevation of extracellular potassium
      concentration. Because K(+) elevation is a component of spinal cord injury, we
      evaluated the extent to which cultured spinal cord astrocytes is affected by K(+)
      levels and obtained evidence suggesting that a Ca(2+)-calmodulin (CaM) protein
      kinase is involved in the K(+)-induced increased coupling. Exposure of astrocytes
      to high K(+) solutions induced a dose-dependent increase in dye coupling; such
      increased coupling was greatly attenuated by reducing extracellular Ca(2+)
      concentration, prevented by nifedipine, and potentiated by Bay-K-8644. These
      results indicate that K(+)-induced increased coupling is mediated by a signaling
      pathway that is dependent on the influx of Ca(2+) through L-type Ca(2+) channels.
      Evidence supporting the participation of the CaM kinase pathway on K(+)-induced
      increased coupling was obtained in experiments showing that calmidazolium and KN
      93 totally prevented the increase in dye and electrical coupling induced by high
      K(+) solutions. Because no changes in connexin43 expression levels or
      distribution were observed in astrocytes exposed to high K(+) solutions, we
      propose that the increased junctional communication is related to an increased
      number of active channels within gap junction plaques.

PMID- 11517254
TI  - Modeling circadian oscillations with interlocking positive and negative feedback
      loops.
AB  - Both positive and negative feedback loops of transcriptional regulation have been
      proposed to be important for the generation of circadian rhythms. To test the
      sufficiency of the proposed mechanisms, two differential equation-based models
      were constructed to describe the Neurospora crassa and Drosophila melanogaster
      circadian oscillators. In the model of the Neurospora oscillator, FRQ suppresses
      frq transcription by binding to a complex of the transcriptional activators WC-1
      and WC-2, thus yielding negative feedback. FRQ also activates synthesis of WC-1,
      which in turn activates frq transcription, yielding positive feedback. In the
      model of the Drosophila oscillator, PER and TIM are represented by a "lumped"
      variable, "PER." PER suppresses its own transcription by binding to the
      transcriptional regulator dCLOCK, thus yielding negative feedback. PER also binds
      to dCLOCK to de-repress dclock, and dCLOCK in turn activates per transcription,
      yielding positive feedback. Both models displayed circadian oscillations that
      were robust to parameter variations and to noise and that entrained to simulated
      light/dark cycles. Circadian oscillations were only obtained if time delays were
      included to represent processes not modeled in detail (e.g., transcription and
      translation). In both models, oscillations were preserved when positive feedback
      was removed.

PMID- 11517255
TI  - Alcohol hypersensitivity, increased locomotion, and spontaneous myoclonus in mice
      lacking the potassium channels Kv3.1 and Kv3.3.
AB  - The Shaw-like potassium (K(+)) channels Kv3.1 and Kv3.3 are widely coexpressed in
      distinct neuronal populations in the CNS, possibly explaining the relatively
      "mild" phenotypes of the Kv3.1 and the Kv3.3 single mutant. Kv3.1-deficient mice
      show increased cortical gamma- and decreased delta-oscillations (Joho et al.,
      1997, 1999); otherwise, the Kv3.1-mutant phenotype is relatively subtle (Ho et
      al., 1997; Sanchez et al., 2000). Kv3.3-deficient mice display no overt phenotype
      (Chan, 1997). To investigate whether Kv3.1 and Kv3.3 K(+) channels are
      functionally redundant, we generated the Kv3.1/Kv3.3 double mutant. Kv3.1/Kv3.3
      deficient mice were born at the expected Mendelian frequencies indicating that
      neither Kv3.1 nor Kv3.3 K(+) channels are essential for embryonic development.
      Although there are no obvious changes in gross brain anatomy, adult Kv3.1/Kv3.3
      deficient mice display severe ataxia, tremulous movements, myoclonus, and
      hypersensitivity to ethanol. Mice appear unbalanced when moving, whereas at rest
      they exhibit whole-body jerks every few seconds. In spite of the severe motor
      impairment, Kv3.1/Kv3.3-deficient mice are hyperactive, show increased
      exploratory activity, and display no obvious learning or memory deficit.
      Myoclonus, tremor, and ethanol hypersensitivity are only seen in the double
      homozygous Kv3.1/Kv3.3-deficient mice, whereas increased locomotor and
      exploratory activity are also present in double-heterozygous mice. The graded
      penetrance of mutant traits appears to depend on the number of null alleles,
      suggesting that some of the distinct phenotypic traits visible in the absence of
      Kv3.1 and Kv3.3 K(+) channels are unrelated and may be caused by localized
      dysfunction in different brain regions.

PMID- 11517256
TI  - Three-dimensional comparison of ultrastructural characteristics at depressing and
      facilitating synapses onto cerebellar Purkinje cells.
AB  - Cerebellar Purkinje cells receive two distinctive types of excitatory inputs.
      Climbing fiber (CF) synapses have a high probability of release and show paired
      pulse depression (PPD), whereas parallel fiber (PF) synapses facilitate and have
      a low probability of release. We examined both types of synapses using serial
      electron microscopic reconstructions in 15-d-old rats to look for anatomical
      correlates of these differences. PF and CF synapses were distinguishable by their
      overall ultrastructural organization. There were differences between PF and CF
      synapses in how many release sites were within 1 microm of a mitochondrion (67 vs
      84%) and in the degree of astrocytic ensheathment (67 vs 94%). However, the
      postsynaptic density sizes for both types of synapses were similar (0.13-0.14
      microm(2)). For both types of synapses, we counted the number of docked vesicles
      per release site to test whether this number determines the probability of
      release and synaptic plasticity. PF and CF synapses had the same number of
      anatomically docked vesicles (7-8). The number of docked vesicles at the CF does
      not support a simple model of PPD in which release of a single vesicle during the
      first pulse depletes the anatomically docked vesicle pool at a synapse.
      Alternatively, only a fraction of anatomically docked vesicles may be release
      ready, or PPD could result from multivesicular release at each site. Similarities
      in the number of docked vesicles for PF and CF synapses indicate that differences
      in probability of release are unrelated to the number of anatomically docked
      vesicles at these synapses.

PMID- 11517257
TI  - Multiple amidated neuropeptides are required for normal circadian locomotor
      rhythms in Drosophila.
AB  - In Drosophila, the amidated neuropeptide pigment dispersing factor (PDF) is
      expressed by the ventral subset of lateral pacemaker neurons and is required for
      circadian locomotor rhythms. Residual rhythmicity in pdf mutants likely reflects
      the activity of other neurotransmitters. We asked whether other neuropeptides
      contribute to such auxiliary mechanisms. We used the gal4/UAS system to create
      mosaics for the neuropeptide amidating enzyme PHM; amidation is a highly specific
      and widespread modification of secretory peptides in Drosophila. Three different
      gal4 drivers restricted PHM expression to different numbers of peptidergic
      neurons. These mosaics displayed aberrant locomotor rhythms to degrees that
      paralleled the apparent complexity of the spatial patterns. Certain PHM mosaics
      were less rhythmic than pdf mutants and as severe as per mutants. Additional gal4
      elements were added to the weakly rhythmic PHM mosaics. Although adding pdf-gal4
      provided only partial improvement, adding the widely expressed tim-gal4 largely
      restored rhythmicity. These results indicate that, in Drosophila, peptide
      amidation is required for neuropeptide regulation of behavior. They also support
      the hypothesis that multiple amidated neuropeptides, acting upstream, downstream,
      or in parallel to PDF, help organize daily locomotor rhythms.

PMID- 11517258
TI  - Ataxia telangiectasia mutated-dependent apoptosis after genotoxic stress in the
      developing nervous system is determined by cellular differentiation status.
AB  - Ataxia-telangiectasia (A-T) is a neurodegenerative syndrome resulting from
      dysfunction of ATM (ataxia telangiectasia mutated). The molecular details of ATM
      function in the nervous system are unclear, although the neurological lesions in
      A-T are probably developmental because they appear during childhood. The nervous
      systems of Atm-null mice show a pronounced defect in apoptosis that is induced by
      DNA damage, suggesting that ATM may function to eliminate DNA-damaged neurons.
      Here we show that Atm-dependent apoptosis occurs at discrete stages of
      neurogenesis. Analysis of gamma-irradiated mouse embryos showed that Atm
      dependent apoptosis occurred only in the postmitotic populations that were
      present in the neuroepithelial subventricular zone of the developing nervous
      system. Notably, Atm deficiency did not prevent radiation-induced apoptosis in
      multipotent precursor cells residing in the proliferating ventricular zone. Atm
      dependent apoptosis required p53 and coincided with the specific phosphorylation
      of p53 and caspase-3 activation. Thus, these data show that Atm functions early
      in neurogenesis and underscore the selective requirement for Atm in eliminating
      damaged postmitotic neural cells. Furthermore, these data demonstrate that the
      differentiation status of neural cells is a critical determinant in the
      activation of certain apoptotic pathways.

PMID- 11517259
TI  - Spike frequency decoding and autonomous activation of Ca2+-calmodulin-dependent
      protein kinase II in dorsal root ganglion neurons.
AB  - Autonomous activation of calcium-calmodulin kinase (CaMKII) has been proposed as
      a molecular mechanism for decoding Ca(2+) spike frequencies resulting from action
      potential firing, but this has not been investigated in intact neurons. This was
      studied in mouse DRG neurons in culture using confocal measurements of
      [Ca(2+)](i) and biochemical measurements of CaMKII autophosphorylation and
      autonomous activity. Using electrical stimulation at different frequencies, we
      find that CaMKII autonomous activity reached near maximal levels after
      approximately 45 impulses, regardless of firing frequency (1-10 Hz), and
      autonomous activity declined with prolonged stimulation. Frequency-dependent
      activation of CaMKII was limited to spike frequencies in the range of 0.1-1 Hz,
      despite marked increases in [Ca(2+)](i) at higher frequencies (1-30 Hz). The high
      levels of autonomous activity measured before stimulation and the relatively long
      duration of Ca(2+) spikes induced by action potentials ( approximately 300 msec)
      are consistent with the lower frequency range of action potential decoding by
      CaMKII. The high autonomous activity under basal conditions was associated with
      extracellular [Ca(2+)], independently from changes in [Ca(2+)](i), and unrelated
      to synaptic or spontaneous impulse activity. CaMKII autonomous activity in
      response to brief bursts of action potentials correlated better with the
      frequency of Ca(2+) transients than with the concentration of [Ca(2+)](i). In
      conclusion, CaMKII may decode frequency-modulated responses between 0.1 and 1 Hz
      in these neurons, but other mechanisms may be required to decode higher
      frequencies. Alternatively, CaMKII may mediate high-frequency responses in
      subcellular microdomains in which the enzyme is maintained at a low level of
      autonomous activity or the Ca(2+) transients have faster kinetics.

PMID- 11517260
TI  - Infusion of brain-derived neurotrophic factor into the lateral ventricle of the
      adult rat leads to new neurons in the parenchyma of the striatum, septum,
      thalamus, and hypothalamus.
AB  - The findings that brain-derived neurotrophic factor (BDNF) promotes in vitro the
      survival and/or differentiation of postnatal subventricular zone (SVZ) progenitor
      cells and increases in vivo the number of the newly generated neurons in the
      adult rostral migratory stream and olfactory bulb prompted us to investigate
      whether the infusion of BDNF influences the proliferation and/or differentiation
      of cells in other regions of the adult forebrain. We examined the distribution
      and phenotype of newly generated cells in the adult rat forebrain 16 d after
      intraventricular administration of BDNF in conjunction with the cell
      proliferation marker bromodeoxyuridine (BrdU) for 12 d. BDNF infusion resulted in
      numerous BrdU(+) cells, not only in the SVZ lining the infused lateral ventricle,
      but moreover, in specific parenchymal structures lining the lateral and third
      ventricles, including the striatum and septum, as well as the thalamus and
      hypothalamus, in which neurogenesis had never been demonstrated previously during
      adulthood. In each region, newly generated cells expressed the neuronal marker
      microtubule-associated protein-2, or neuron-specific tubulin, identified by the
      antibody TuJ1. The percentage of the newly generated cells expressing TuJ1 ranged
      from 27 to 42%, suggesting that the adult forebrain has a more profound capacity
      to produce neurons than recognized previously. The extent of cell proliferation
      after BDNF infusion was correlated with the level of expression of full-length
      TrkB, the high-affinity receptor for BDNF, despite the fact that the BrdU(+)
      cells were not themselves TrkB(+). Collectively, our results demonstrate that the
      adult brain parenchyma may recruit and/or generate new neurons, which could
      replace those lost as a result of injury or disease.

PMID- 11517261
TI  - Adenoviral brain-derived neurotrophic factor induces both neostriatal and
      olfactory neuronal recruitment from endogenous progenitor cells in the adult
      forebrain.
AB  - Neural progenitor cells persist throughout the adult forebrain subependyma, and
      neurons generated from them respond to brain-derived neurotrophic factor (BDNF)
      with enhanced maturation and survival. To induce neurogenesis from endogenous
      progenitors, we overexpressed BDNF in the adult ventricular zone by transducing
      the forebrain ependyma to constitutively express BDNF. We constructed a
      bicistronic adenovirus bearing BDNF under cytomegalovirus (CMV) control, and
      humanized green fluorescent protein (hGFP) under internal ribosomal entry site
      (IRES) control. This AdCMV:BDNF:IRES:hGFP (AdBDNF) was injected into the lateral
      ventricles of adult rats, who were treated for 18 d thereafter with the mitotic
      marker bromodeoxyuridine (BrdU). Three weeks after injection, BDNF averaged 1
      microg/gm in the CSF of AdBDNF-injected animals but was undetectable in control
      CSF. In situ hybridization demonstrated BDNF and GFP mRNA expression restricted
      to the ventricular wall. In AdBDNF-injected rats, the olfactory bulb exhibited a
      >2.4-fold increase in the number of BrdU(+)-betaIII-tubulin(+) neurons, confirmed
      by confocal imaging, relative to AdNull (AdCMV:hGFP) controls. Importantly,
      AdBDNF-associated neuronal recruitment to the neostriatum was also noted, with
      the treatment-induced addition of BrdU(+)-NeuN(+)-betaIII-tubulin(+) neurons to
      the caudate putamen. Many of these cells also expressed glutamic acid
      decarboxylase, cabindin-D28, and DARPP-32 (dopamine and cAMP-regulated
      phosphoprotein of 32 kDa), markers of medium spiny neurons of the neostriatum.
      These newly generated neurons survived at least 5-8 weeks after viral induction.
      Thus, a single injection of adenoviral BDNF substantially augmented the
      recruitment of new neurons into both neurogenic and non-neurogenic sites in the
      adult rat brain. The intraventricular delivery of, and ependymal infection by,
      viral vectors encoding neurotrophic agents may be a feasible strategy for
      inducing neurogenesis from resident progenitor cells in the adult brain.

PMID- 11517262
TI  - Alpha4 integrin is expressed during peripheral nerve regeneration and enhances
      neurite outgrowth.
AB  - We have shown previously that repair in the peripheral nervous system is
      associated with a reversion to an embryonic pattern of alternative splicing of
      the extracellular matrix molecule fibronectin. One of the consequent changes is a
      relative increase in the number of fibronectins expressing the binding site for
      alpha4 integrins. Here we show that alpha4 integrins are expressed on dorsal root
      ganglion neuron cell bodies and growth cones in the sciatic nerve during
      regeneration and that the interaction of alpha4 integrin with alternatively
      spliced isoforms of recombinant fibronectins containing the alpha4 binding site
      enhances neurite outgrowth in dorsal root ganglion neurons. The pheochromocytoma
      (PC12) neuronal cell line, which normally extends neurites poorly on fibronectin,
      does so efficiently when alpha4 is expressed in the cells. Experiments using
      chimeric integrins expressed in PC12 cells show that the alpha4 cytoplasmic
      domain is necessary and sufficient for this enhanced neurite outgrowth. In both
      dorsal root ganglion neurons and PC12 cells the alpha4 cytoplasmic domain is
      tightly linked to the intracellular adapter protein paxillin. These experiments
      suggest an important role for alpha4 integrin and paxillin in peripheral nerve
      regeneration and show how alternative splicing of fibronectin may provide a
      mechanism to enhance repair after injury.

PMID- 11517263
TI  - A mutation of early photoreceptor development, mikre oko, reveals cell-cell
      interactions involved in the survival and differentiation of zebrafish
      photoreceptors.
AB  - To gain insight into mechanisms involved in photoreceptor development, we
      characterized a zebrafish mutation in the mikre oko locus that produces early
      loss of photoreceptor cells. mikre oko photoreceptors lose their elongated
      morphology at the time of wild-type outer segment formation and undergo cell
      death within a few days. To investigate whether this phenotype involves cell-cell
      interaction defects, we performed analysis of genetically mosaic animals.
      Interactions of mikre oko photoreceptors with wild-type cells rescue several
      aspects of the mutant phenotype. When placed in a wild-type environment, mikre
      oko photoreceptor cells retain elongated morphology and survive longer. Moreover,
      although mutant mikre oko photoreceptor outer segments develop only infrequently
      and are usually disorganized, mikre oko cone and rod cells in mosaic retinas
      develop robust outer segments that closely resemble the wild type. In contrast to
      the outer segments, the proximal regions of mikre oko photoreceptor cells,
      including their inner segments, the nuclear regions, and the synaptic termini,
      retain the mutant appearance. mikre oko outer segment rescue is not mediated by
      interactions with the retinal pigment epithelium. These studies demonstrate that
      the differentiation of outer segments is surprisingly independent from the more
      proximal photoreceptor cell features and that outer segment development includes
      retinal pigment epithelium-independent cell-cell interactions.

PMID- 11517264
TI  - p35 and p39 are essential for cyclin-dependent kinase 5 function during
      neurodevelopment.
AB  - Cyclin-dependent kinase 5 (Cdk5) plays a pivotal role in brain development and
      neuronal migration. Cdk5 is abundant in postmitotic, terminally differentiated
      neurons. The ability of Cdk5 to phosphorylate substrates is dependent on
      activation by its neuronal-specific activators p35 and p39. There exist striking
      differences in the phenotypic severity of Cdk5-deficient mice and p35-deficient
      mice. Cdk5-null mutants show a more severe disruption of lamination in the
      cerebral cortex, hippocampus, and cerebellum. In addition, Cdk5-null mice display
      perinatal lethality, whereas p35-null mice are viable. These discrepancies have
      been attributed to the function of other Cdk5 activators, such as p39. To
      understand the roles of p39 and p35, we created p39-null mice and p35/p39
      compound-mutant mice. Interestingly, p39-null mice show no obvious detectable
      abnormalities, whereas p35(-/-)p39(-/-) double-null mutants are perinatal lethal.
      We show here that the p35(-/-)p39(-/-) mutants exhibit phenotypes identical to
      those of the Cdk5-null mutant mice. Other compound-mutant mice with intermediate
      phenotypes allow us to determine the distinct and redundant functions between p35
      and p39. Our data strongly suggest that p35 and p39 are essential for Cdk5
      activity during the development of the nervous system. Thus, p35 and p39 are
      likely to be the principal, if not the only, activators of Cdk5.

PMID- 11517265
TI  - Telencephalic neural progenitors appear to be restricted to regional and glial
      fates before the onset of neurogenesis.
AB  - The contribution of early cell lineage to regional fate in the mammalian
      forebrain remains poorly understood. Previous lineage-tracing studies using
      retroviral methods were only begun at mid-neurogenesis and have suffered from
      region-specific retroviral silencing. We have been able to study cell lineage in
      the telencephalon from the onset of neurogenesis by using ultrasound backscatter
      microscopy to label the forebrain neuroepithelium and a modified retroviral
      lineage library to overcome regional silencing. Our studies suggest that by
      embryonic day 9.5, forebrain clones are primarily restricted to territories
      within anatomically demarcated regional boundaries, such as the cortex, striatum
      and hypothalamus. In addition, we observed a subset of clones that appeared to be
      composed entirely of glia. These observations suggest that both regional and cell
      type restrictions exist within progenitor populations before the first forebrain
      cells become postmitotic.

PMID- 11517266
TI  - Rab3A is required for brain-derived neurotrophic factor-induced synaptic
      plasticity: transcriptional analysis at the population and single-cell levels.
AB  - Brain-derived neurotrophic factor (BDNF) modulates synaptic strength in
      hippocampal neurons, in addition to promoting survival and differentiation. To
      identify genes involved in trophic regulation of synaptic plasticity, we have
      used a multidisciplinary approach of differential display and family-specific
      slot blots in combination with whole-cell patch-clamp recordings of dissociated
      hippocampal neurons. Three hour exposure to BDNF elicited a 2.6-fold increase in
      synaptic charge and a concomitant induction of 11 genes as revealed by
      differential display, including the small GTP-binding vesicular trafficking
      protein Rab3A and the enzyme guanylate cyclase (GC). Slot blot analysis on a
      population of neurons confirmed an average of 3.1-fold induction of these clones.
      In contrast, individual pyramidal-like neurons that were first characterized
      electrophysiologically in the presence of BDNF and subjected to transcriptional
      analysis displayed more robust increases (4.8-fold), emphasizing the neuronal
      heterogeneity. Transcriptional changes of Rab3A and GC were accompanied by
      translational regulation, shown by Western blot analysis. Furthermore, a number
      of GC-associated and Rab3A effector molecules were induced by BDNF at either the
      gene or protein levels. The functional role of Rab3A in BDNF-induced synaptic
      plasticity was assessed using cells derived from Rab3A knock-out mice. These
      neurons failed to show an increase in synaptic charge in response to BDNF at 10
      min; however a late response to BDNF was detected at 20 min. This late response
      was similar in time course to that induced by postsynaptic activation of
      glutamate receptors. Our results demonstrate a requirement for Rab3A and may
      reveal a temporal distinction between presynaptic and postsynaptic mechanisms of
      BDNF-induced synaptic plasticity associated with learning and memory.

PMID- 11517267
TI  - Developmental inhibitory gate controls the relay of activity to the superficial
      layers of the visual cortex.
AB  - A developmental reduction in the radial transmission of synaptic activity has
      been proposed to underlie the end of the critical period for experience-dependent
      modification in layers II/III of the visual cortex. Using paired-pulse
      stimulation, we investigated in visual cortical slices how the propagation of
      synaptic activity to the superficial layers changes during development and how
      this process is affected by sensory experience. The results can be summarized as
      follows. (1) Layers II/III responses to repetitive stimulation of the white
      matter become increasingly depressed between the third and sixth week of
      postnatal development, a time course that parallels the end of the critical
      period. (2) Paired-pulse depression is reduced after dark rearing and also by
      blocking inhibitory synaptic transmission. (3) Paired-pulse depression and its
      regulation by age and sensory experience is more pronounced when stimulation is
      applied to the white matter than when applied to layer IV. Together, these
      results are consistent with the idea that the maturation of intracortical
      inhibition reduces the capability of the cortex to relay incoming high-frequency
      patterns of activity to the supragranular layers.

PMID- 11517268
TI  - Agrin differentially regulates the rates of axonal and dendritic elongation in
      cultured hippocampal neurons.
AB  - In the present study, we examined the role of agrin in axonal and dendritic
      elongation in central neurons. Dissociated hippocampal neurons were grown in the
      presence of either recombinant agrin or antisense oligonucleotides designed to
      block agrin expression. Our results indicate that agrin differentially regulates
      axonal and dendritic growth. Recombinant agrin decreased the rate of elongation
      of main axons but induced the formation of axonal branches. On the other hand,
      agrin induced both dendritic elongation and dendritic branching. Conversely,
      cultured hippocampal neurons depleted of agrin extended longer, nonbranched axons
      and shorter dendrites when compared with controls. These changes in the rates of
      neurite elongation and branching were paralleled by changes in the composition of
      the cytoskeleton. In the presence of agrin, there was an upregulation of the
      expression of microtubule-associated proteins MAP1B, MAP2, and tau. In contrast,
      a downregulation of the expression of these MAPs was detected in agrin-depleted
      cells. Taken collectively, these results suggest an important role for agrin as a
      trigger of the transcription of neuro-specific genes involved in neurite
      elongation and branching in central neurons.

PMID- 11517269
TI  - Conserved function of Caenorhabditis elegans UNC-30 and mouse Pitx2 in
      controlling GABAergic neuron differentiation.
AB  - We are taking a cross-species approach to identify genes that are required for
      mammalian GABAergic neuron differentiation. On the basis of homeodomain
      similarity, the vertebrate Pitx genes appear to be orthologs of unc-30, a
      Caenorhabditis elegans gene necessary for differentiation of the GABAergic
      phenotype of type D neurons. One of the Pitx genes, Pitx2, is expressed in
      regions of GABAergic neurogenesis in the mammalian brain. These observations led
      us to test the functional conservation of the mouse Pitx2 and worm unc-30 genes
      using a rescue assay. Pitx2 rescues the GABAergic differentiation defect and
      partially rescues the axon guidance and behavioral phenotypes of unc-30 mutants,
      indicating a high degree of functional conservation between these evolutionarily
      related genes. Previous studies show that UNC-30 directly regulates the unc
      25/glutamate decarboxylase gene that encodes the enzyme for GABA synthesis. We
      find that the promoter regions of the mouse and human genes coding for the 67 kDa
      glutamate decarboxylase (Gad1) also contain binding sites matching the UNC
      30/Pitx2 consensus binding site sequence. We show that these sites specifically
      bind to Pitx2 protein in vitro and that in transfected neuroblastoma cells, the
      Pitx2 binding sites contribute to the basal activity of the Gad1 promoter.
      Furthermore, in cotransfection experiments, we find that Pitx2 strongly activates
      the Gad1 promoter. These results indicate that Pitx2 may regulate Gad1 expression
      in mammals, suggesting a new role for this key developmental transcription factor
      as a regulator of GABAergic differentiation during mammalian neural development.
      Our results suggest that some of the mechanisms regulating GABAergic
      differentiation are evolutionarily conserved.

PMID- 11517270
TI  - The cortical representation of the hand in macaque and human area S-I: high
      resolution optical imaging.
AB  - High-resolution images of the somatotopic hand representation in macaque monkey
      primary somatosensory cortex (area S-I) were obtained by optical imaging based on
      intrinsic signals. To visualize somatotopic maps, we imaged optical responses to
      mild tactile stimulation of each individual fingertip. The activation evoked by
      stimulation of a single finger was strongest in a narrow transverse band (
      approximately 1 x 4 mm) across the postcentral gyrus. As expected, a sequential
      organization of these bands was found. However, a significant overlap, especially
      for the activated areas of fingers 3-5, was found. Surprisingly, in addition to
      the finger-specific domains, we found that for each of the fingers, weak
      stimulation activated also a second "common patch" of cortex, located just
      medially to the representation of the finger. These results were confirmed by
      targeted multiunit and single-unit recordings guided by the optical maps. The
      maps remained very stable over many hours of recording. By optimizing the imaging
      procedures, we were able to obtain the functional maps extremely rapidly (e.g.,
      the map of five fingers in the macaque monkey could be obtained in as little as 5
      min). Furthermore, we describe the intraoperative optical imaging of the hand
      representation in the human brain during neurosurgery and then discuss the
      implications of the present results for the spatial resolution accomplishable by
      other neuroimaging techniques, relying on responses of the microcirculation to
      sensory-evoked electrical activity. This study demonstrates the feasibility of
      using high-resolution optical imaging to explore reliably short- and long-term
      plasticity of cortical representations, as well as for applications in the
      clinical setting.

PMID- 11517271
TI  - An avian basal ganglia pathway essential for vocal learning forms a closed
      topographic loop.
AB  - The mammalian basal ganglia-thalamocortical pathway is important for motor
      control, motor learning, and cognitive functions. It contains parallel, closed
      loops, at least some of which are organized topographically and in a modular
      manner. Songbirds have a circuit specialized for vocal learning, the anterior
      forebrain pathway (AFP), forming a basal ganglia loop with only three stations:
      the pallial ("cortex-like") lateral magnocellular nucleus of the anterior
      neostriatum (lMAN), the basal ganglia structure area X, and the medial portion of
      the dorsolateral thalamic nucleus (DLM). Several properties of this pathway
      resemble those of its mammalian counterpart, but it is unknown whether all
      projections in the loop are topographically organized, and if so, whether
      topography is maintained through the entire loop. After small single- or dual
      tracer injections into area X and/or the lMAN of adult zebra finches, we found
      that the area X to DLM projection is topographically organized, and we confirmed
      the topography for all other AFP projections. Quantitative analysis suggests
      maintained topography throughout the loop. To test this directly, we injected
      different tracers into corresponding areas in lMAN and area X. We found somata
      retrogradely labeled from lMAN and terminals anterogradely labeled from area X
      occupying the same region of DLM. Many labeled somata were tightly surrounded by
      tracer-labeled terminals, indicating the microscopically closed nature of the AFP
      loop. Thus, like mammals, birds have at least one closed, topographic loop
      traversing the basal ganglia, thalamus, and pallium. Each such loop could serve
      as a computational unit for motor or cognitive functions.

PMID- 11517272
TI  - Pharmacological modulation of behavioral and neuronal correlates of repetition
      priming.
AB  - In this experiment we address the pharmacological modulation of repetition
      priming, a basic form of learning, using event-related functional magnetic
      resonance imaging. We measured brain activity in a word-stem completion paradigm
      in which, before study, volunteers were given either placebo, lorazepam (2 mg
      orally), or scopolamine (0.4 mg, i.v.). Relative to placebo, both drugs
      attenuated the behavioral expression of priming. Repetition was associated with a
      decreased neuronal response in left extrastriate, left middle frontal, and left
      inferior frontal cortices in the placebo group. Both drugs abolished these
      "repetition suppression" effects. By showing a concurrence of behavioral and
      neuronal modulations, the results suggest that GABAergic and cholinergic systems
      influence the neuronal plasticity necessary for repetition priming.

PMID- 11517273
TI  - Relationship between the appearance of symptoms and the level of nigrostriatal
      degeneration in a progressive 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
      lesioned macaque model of Parkinson's disease.
AB  - The concept of a threshold of dopamine (DA) depletion for onset of Parkinson's
      disease symptoms, although widely accepted, has, to date, not been determined
      experimentally in nonhuman primates in which a more rigorous definition of the
      mechanisms responsible for the threshold effect might be obtained. The present
      study was thus designed to determine (1) the relationship between Parkinsonian
      symptom appearance and level of degeneration of the nigrostriatal pathway and (2)
      the concomitant presynaptic and postsynaptic striatal response to the
      denervation, in monkeys treated chronically with 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine according to a regimen that produces a progressive
      Parkinsonian state. The kinetics of the nigrostriatal degeneration described
      allow the determination of the critical thresholds associated to symptom
      appearance, these were a loss of 43.2% of tyrosine hydroxylase-immunopositive
      neurons at the nigral level and losses of 80.3 and 81.6% DA transporter binding
      and DA content, respectively, at the striatal level. Our data argue against the
      concept that an increase in DA metabolism could act as an efficient adaptive
      mechanism early in the disease progress. Surprisingly, the D(2)-like DA receptor
      binding showed a biphasic regulation in relation to the level of striatal
      dopaminergic denervation, i.e., an initial decrease in the presymptomatic period
      was followed by an upregulation of postsynaptic receptors commencing when
      striatal dopaminergic homeostasis is broken. Further in vivo follow-up of the
      kinetics of striatal denervation in this, and similar, experimental models is now
      needed with a view to developing early diagnosis tools and symptomatic therapies
      that might enhance endogenous compensatory mechanisms.

PMID- 11517274
TI  - Barrel pattern formation requires serotonin uptake by thalamocortical afferents,
      and not vesicular monoamine release.
AB  - Thalamocortical neurons innervating the barrel cortex in neonatal rodents
      transiently store serotonin (5-HT) in synaptic vesicles by expressing the plasma
      membrane serotonin transporter (5-HTT) and the vesicular monoamine transporter
      (VMAT2). 5-HTT knock-out (ko) mice reveal a nearly complete absence of 5-HT in
      the cerebral cortex by immunohistochemistry, and of barrels, both at P7 and
      adulthood. Quantitative electron microscopy reveals that 5-HTT ko affects neither
      the density of synapses nor the length of synaptic contacts in layer IV. VMAT2 ko
      mice, completely lacking activity-dependent vesicular release of monoamines
      including 5-HT, also show a complete lack of 5-HT in the cortex but display
      largely normal barrel fields, despite sometimes markedly reduced postnatal
      growth. Transient 5-HTT expression is thus required for barrel pattern formation,
      whereas activity-dependent vesicular 5-HT release is not.

PMID- 11517275
TI  - Dendritic arborizations of the rat substantia nigra pars reticulata neurons:
      spatial organization and relation to the lamellar compartmentation of striato
      nigral projections.
AB  - The cerebral cortex provides a major source of inputs to the basal ganglia. As
      has been well documented, the topography of corticostriatal projections
      subdivides the striatum into a mosaic of functionally distinct sectors. How
      information flow from these striatal sectors remains segregated or not within
      basal ganglia output nuclei has to be established. Electrophysiologically
      identified neurons of the rat substantia nigra pars reticulata were labeled by
      juxtacellular injection of Neurobiotin, and the spatial organization of their
      dendritic arborizations was analyzed in relation to the projection fields of
      individual striatal sectors. Thirty-nine nigral neurons located in the projection
      territory of the distinct striatal sensorimotor sectors were reconstructed. The
      data show that the dendritic arborizations of nigral neurons conform to the
      geometry of striato-nigral projections. Like striatal projections, the
      arborizations formed a series of curved laminas enveloping a dorsolaterally
      located core. Although dendritic fields of the neurons lying in the laminae were
      flat, those located in the core were spherical or cylindrical, thereby conforming
      to the shape of the striatal projection fields. This remarkable alignment between
      the dendritic arborizations of nigral neurons and the projection fields from
      individual striatal districts supports the concept of a parallel architecture of
      the striato-nigral circuits. However, pars reticulata neurons usually extend part
      of their dendrites within adjacent striatal projection fields, thereby ensuring a
      continuum between channels. The extension of the dendritic arborizations within
      the striatal projection fields suggests that nigral neurons integrate the
      information that is relevant for the completion of the specific motor behavior
      they control.

PMID- 11517276
TI  - Intra-amygdala blockade of the NR2B subunit of the NMDA receptor disrupts the
      acquisition but not the expression of fear conditioning.
AB  - The lateral nucleus of the amygdala (LA) is an essential component of the neural
      circuitry underlying Pavlovian fear conditioning. Although blockade of NMDA
      receptors in LA and adjacent areas before training disrupts the acquisition of
      fear conditioning, blockade before testing also often disrupts the expression of
      fear responses. With this pattern of results, it is not possible to distinguish a
      contribution of NMDA receptors to plasticity from a role in synaptic
      transmission. In past studies, NMDA blockade has been achieved using the
      antagonist d,l-2-amino-5-phosphovalerate, which blocks the entire heteromeric
      receptor complex. The present experiments examined the effects of selective
      blockade of the NR2B subunit of the NMDA receptor in LA using the selective
      antagonist ifenprodil. Systemic injections of ifenprodil before training led to a
      dose-dependent impairment in the acquisition of auditory and contextual fear
      conditioning, whereas injections before testing had no effect. Intra-amygdala
      infusions of ifenprodil mirrored these results and, in addition, showed that the
      effects are attributable to a disruption of fear learning rather than a
      disruption of memory consolidation. NMDA receptors in LA are thus involved in
      fear conditioning, and the NR2B subunit appears to make unique contributions to
      the underlying plasticity.

PMID- 11517277
TI  - A role for dopamine D1 receptors of the nucleus accumbens shell in conditioned
      taste aversion learning.
AB  - The involvement of dopamine (DA) in conditioned taste aversion (CTA) learning was
      studied with saccharin or sucrose as the conditioned stimulus (CS) and
      intraperitoneal lithium as the unconditioned stimulus (US). The dopamine D(1)
      antagonist R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3
      benzazepine hydrochloride (SCH 23390) (12.5-50 microg/kg, s.c.), given 5 min
      after the CS, impaired the acquisition of CTA in a paradigm consisting of three
      or a single CS-lithium association. SCH 23390 failed to impair CTA acquisition
      given 45 min after, 30 min before, or right before the CS. (-)-trans
      6,7,7a,8,9,13b-hexahydro-3-chloro-2-hydroxy-N-methyl-5a-benzo-(d)-naphtho-(2,1b)
      azepine (SCH 39166) (12.5-50.0 microg/kg, s.c), a SCH 23390 analog that does not
      bind to 5HT(2) receptors, also impaired CTA. No significant impairment of CTA was
      obtained after administration of the specific D(2)/D(3) antagonist raclopride
      (100 and 300 microg/kg, s.c.). The ability of SCH 23390 to impair CTA learning
      was confirmed by its ability to reduce the conditional aversive reactions to a
      gustatory CS (sweet chocolate) as estimated in a taste reactivity paradigm. SCH
      39166 impaired CTA also when infused in the nucleus accumbens (NAc) shell 5 min
      after the CS. No impairment was obtained from the NAc core or from the bed
      nucleus stria terminalis. The results indicate that D(1) receptor blockade
      impairs CTA learning by disrupting the formation of a short-term memory trace of
      the gustatory CS and that endogenous dopamine acting on D(1) receptors in the NAc
      shell plays a role in short-term memory processes related to associative
      gustatory learning.

PMID- 11517278
TI  - Neural coding mechanisms underlying perceived roughness of finely textured
      surfaces.
AB  - Combined psychophysical and neurophysiological studies have shown that the
      perceived roughness of surfaces with element spacings of >1 mm is based on
      spatial variation in the firing rates of slowly adapting type 1 (SA1) afferents
      (mean absolute difference in firing rates between SA1 afferents with receptive
      fields separated by approximately 2 mm). The question addressed here is whether
      this mechanism accounts for the perceived roughness of surfaces with element
      spacings of <1 mm. Twenty triangular and trapezoidal gratings plus a smooth
      surface were used as stimulus patterns [spatial periods, 0.1-2.0 mm; groove
      widths (GWs), 0.1-2.0 mm; and ridge widths (RWs), 0-1.0 mm]. In the human
      psychophysical studies, we found that the following equation described the mean
      roughness magnitude estimates of the subjects accurately (0.99 correlation): 0.2
      + 1.6GW - 0.5RW - 0.25GW(2). In the neurophysiological studies, these surfaces
      were scanned across the receptive fields of SA1, rapidly adapting, and Pacinian
      (PC) afferents, innervating the glabrous skin of anesthetized macaque monkeys.
      SA1 spatial variation was highly correlated (0.97) with human roughness
      judgments. There was no consistent relationship between PC responses and
      roughness judgments; PC afferents responded strongly and almost equally to all of
      the patterns. Spatial variation in SA1 firing rates is the only neural code that
      accounts for the perceived roughness of surfaces with finely and coarsely spaced
      elements. When surface elements are widely spaced, the spatial variation in
      firing rates is determined primarily by the surface pattern; when the elements
      are finely spaced, the variation in firing rates between SA1 afferents is
      determined by stochastic variation in spike rates.

PMID- 11517279
TI  - Eye-hand coordination in object manipulation.
AB  - We analyzed the coordination between gaze behavior, fingertip movements, and
      movements of the manipulated object when subjects reached for and grasped a bar
      and moved it to press a target-switch. Subjects almost exclusively fixated
      certain landmarks critical for the control of the task. Landmarks at which
      contact events took place were obligatory gaze targets. These included the grasp
      site on the bar, the target, and the support surface where the bar was returned
      after target contact. Any obstacle in the direct movement path and the tip of the
      bar were optional landmarks. Subjects never fixated the hand or the moving bar.
      Gaze and hand/bar movements were linked concerning landmarks, with gaze leading.
      The instant that gaze exited a given landmark coincided with a kinematic event at
      that landmark in a manner suggesting that subjects monitored critical kinematic
      events for phasic verification of task progress and subgoal completion. For both
      the obstacle and target, subjects directed saccades and fixations to sites that
      were offset from the physical extension of the objects. Fixations related to an
      obstacle appeared to specify a location around which the extending tip of the bar
      should travel. We conclude that gaze supports hand movement planning by marking
      key positions to which the fingertips or grasped object are subsequently
      directed. The salience of gaze targets arises from the functional sensorimotor
      requirements of the task. We further suggest that gaze control contributes to the
      development and maintenance of sensorimotor correlation matrices that support
      predictive motor control in manipulation.

PMID- 11517280
TI  - Nociceptor sensitization by extracellular signal-regulated kinases.
AB  - Inflammatory pain, characterized by a decrease in mechanical nociceptive
      threshold (hyperalgesia), arises through actions of inflammatory mediators, many
      of which sensitize primary afferent nociceptors via G-protein-coupled receptors.
      Two signaling pathways, one involving protein kinase A (PKA) and one involving
      the epsilon isozyme of protein kinase C (PKCepsilon), have been implicated in
      primary afferent nociceptor sensitization. Here we describe a third, independent
      pathway that involves activation of extracellular signal-regulated kinases (ERKs)
      1 and 2. Epinephrine, which induces hyperalgesia by direct action at beta(2)
      adrenergic receptors on primary afferent nociceptors, stimulated phosphorylation
      of ERK1/2 in cultured rat dorsal root ganglion cells. This was inhibited by a
      beta(2)-adrenergic receptor blocker and by an inhibitor of mitogen and
      extracellular signal-regulated kinase kinase (MEK), which phosphorylates and
      activates ERK1/2. Inhibitors of G(i/o)-proteins, Ras farnesyltransferases, and
      MEK decreased epinephrine-induced hyper-algesia. In a similar manner,
      phosphorylation of ERK1/2 was also decreased by these inhibitors. Local injection
      of dominant active MEK produced hyperalgesia that was unaffected by PKA or
      PKCepsilon inhibitors. Conversely, hyperalgesia produced by agents that activate
      PKA or PKCepsilon was unaffected by MEK inhibitors. We conclude that a Ras-MEK
      ERK1/2 cascade acts independent of PKA or PKCepsilon as a novel signaling pathway
      for the production of inflammatory pain. This pathway may present a target for a
      new class of analgesic agents.

PMID- 11517281
TI  - Nociceptin reduces epileptiform events in CA3 hippocampus via presynaptic and
      postsynaptic mechanisms.
AB  - The opiate-like peptide nociceptin/orphanin FQ (Noc) and its receptor [opiate
      receptor-like receptor (ORL-1)] are highly expressed in the hippocampus. Noc has
      inhibitory postsynaptic actions in CA1, CA3, and the dentate and seems to lack
      the disinhibitory, excitatory actions demonstrated for some opiate peptides in
      the hippocampus. The CA3 hippocampal region is important in the generation of
      hippocampal seizures. Therefore, we tested the action of Noc on spontaneous
      epileptiform activity recorded extracellularly or intracellularly in CA3 and
      generated by removal of Mg(2+) from the bathing solution or by raising
      extracellular K(+) from 3.5 to 7.5 mm. Superfusion of Noc robustly depressed
      spontaneous bursting without desensitization. The ORL-1 antagonist
      [Phe(1)Psi(CH(2)-NH)Gly(2)]NC(1-13)NH(2) (1-2 microm) greatly attenuated the
      reduction of spontaneous bursting by Noc. To characterize the cellular mechanism
      of action of Noc, we recorded intracellularly from CA3 pyramidal neurons. Noc
      reduced EPSCs evoked by stimulating either mossy or associational/commissural
      fibers. Analysis of miniature EPSCs using whole-cell voltage-clamp recording
      suggests that Noc acts presynaptically to inhibit glutamate release. This is the
      first demonstration of a presynaptic effect for Noc in the hippocampus. Noc also
      increased K(+) currents in CA3 pyramidal neurons, including the voltage-sensitive
      M-current. Blocking the M-current with linopirdine increased the duration of
      individual CA3 bursts but did not attenuate Noc-mediated inhibition of bursting.
      Thus, Noc acts via multiple mechanisms to reduce excitation in CA3. However, Noc
      inhibition of epileptiform events is not dependent on augmentation of the M
      current.

PMID- 11517282
TI  - Acetylcholine mediates the estrogen-induced increase in NMDA receptor binding in
      CA1 of the hippocampus and the associated improvement in working memory.
AB  - Elevated levels of circulating estrogen in female rats result in increased spine
      and synapse density and parallel increases in NMDA receptor binding in area CA1
      of the hippocampus. Estrogen also influences cholinergic neurochemistry in the
      basal forebrain and hippocampus. The objectives of the present study were to
      determine the role of acetylcholine in the estrogen-induced increase in NMDA
      receptor binding in CA1 of the hippocampus and to investigate the relationship
      between increased NMDA receptor binding in CA1 and performance on a task of
      working memory. In the current experiments, elevating endogenous levels of
      acetylcholine in ovariectomized rats by 3 d of continuous administration of
      physostigmine, an acetylcholinesterase inhibitor, increased NMDA receptor binding
      in CA1 as measured by quantitative autoradiography. This increase was comparable
      with the increase in NMDA receptor binding induced by injections of estradiol
      benzoate 72 and 48 hr before death. Additionally, the administration of 5,11
      dihydro-8-chloro-11-[[4-[3-[(2,2-dimethyl-1-oxopentyl)ethylamino]propyl]-1
      piperidinyl]acetyl]-6H-pyrido[2,3-b][1,4]benzodiazepin-6-one (BIBN 99), an M2
      receptor antagonist, blocked the ability of both estrogen and physostigmine to
      increase NMDA receptor binding. The regimen of estradiol replacement that was
      demonstrated to increase NMDA receptor binding in CA1 of ovariectomized rats also
      improved arm-choice accuracy in a working memory task in an eight-arm radial
      maze. The estrogen-induced improvement in working memory performance was blocked
      by BIBN 99, which also blocked the increase in NMDA receptor binding. These
      results indicate that acetylcholine acts at M2 muscarinic receptors to mediate
      the estrogen-induced increase in NMDA receptor binding in CA1 of the hippocampus
      as well as the associated improvement in working memory.

PMID- 11517283
TI  - Transfer of visual motion information via graded synapses operates linearly in
      the natural activity range.
AB  - Synaptic transmission between a graded potential neuron and a spiking neuron was
      investigated in vivo using sensory stimulation instead of artificial excitation
      of the presynaptic neuron. During visual motion stimulation, individual
      presynaptic and postsynaptic neurons in the brain of the fly were
      electrophysiologically recorded together with concentration changes of
      presynaptic calcium (Delta[Ca(2+)](pre)). Preferred-direction motion leads to
      depolarization of the presynaptic neuron. It also produces pronounced increases
      in [Ca(2+)](pre) and the postsynaptic spike rate. Motion in the opposite
      direction was associated with hyperpolarization of the presynaptic cell but only
      a weak reduction in [Ca(2+)](pre) and the postsynaptic spike rate. Apart from
      this rectification, the relationships between presynaptic depolarizations,
      Delta[Ca(2+)](pre), and postsynaptic spike rates are, on average, linear over the
      entire range of activity levels that can be elicited by sensory stimulation.
      Thus, the inevitably limited range in which the gain of overall synaptic signal
      transfer is constant appears to be adjusted to sensory input strengths.

PMID- 11517284
TI  - Responses of magnocellular neurons to osmotic stimulation involves coactivation
      of excitatory and inhibitory input: an experimental and theoretical analysis.
AB  - How does a neuron, challenged by an increase in synaptic input, display a
      response that is independent of the initial level of activity? Here we show that
      both oxytocin and vasopressin cells in the supraoptic nucleus of normal rats
      respond to intravenous infusions of hypertonic saline with gradual, linear
      increases in discharge rate. In hyponatremic rats, oxytocin and vasopressin cells
      also responded linearly to intravenous infusions of hypertonic saline but with
      much lower slopes. The linearity of response was surprising, given both the
      expected nonlinearity of neuronal behavior and the nonlinearity of the oxytocin
      secretory response to such infusions. We show that a simple computational model
      can reproduce these responses well, but only if it is assumed that hypertonic
      infusions coactivate excitatory and inhibitory synaptic inputs. This hypothesis
      was tested first by applying the GABA(A) antagonist bicuculline to the dendritic
      zone of the supraoptic nucleus by microdialysis. During local blockade of GABA
      inputs, the response of oxytocin cells to hypertonic infusion was greatly
      enhanced. We then went on to directly measure GABA release in the supraoptic
      nucleus during hypertonic infusion, confirming the predicted rise. Together, the
      results suggest that hypertonic infusions lead to coactivation of excitatory and
      inhibitory inputs and that this coactivation may confer appropriate
      characteristics on the output behavior of oxytocin cells. The nonlinearity of
      oxytocin secretion that accompanies the linear increase in oxytocin cell firing
      rate reflects frequency-facilitation of stimulus-secretion coupling at the
      neurohypophysis.

PMID- 11517285
TI  - Information conveyed by onset transients in responses of striate cortical
      neurons.
AB  - Normal eye movements ensure that the visual world is seen episodically, as a
      series of often stationary images. In this paper we characterize the responses of
      neurons in striate cortex to stationary grating patterns presented with abrupt
      onset. These responses are distinctive. In most neurons the onset of a grating
      gives rise to a transient discharge that decays with a time constant of 100 msec
      or less. The early stages of response have higher contrast gain and higher
      response gain than later stages. Moreover, the variability of discharge during
      the onset transient is disproportionately low. These factors together make the
      onset transient an information-rich component of response, such that the
      detectability and discriminability of stationary gratings grows rapidly to an
      early peak, within 150 msec of the onset of the response in most neurons. The
      orientation selectivity of neurons estimated from the first 150 msec of discharge
      to a stationary grating is indistinguishable from the orientation selectivity
      estimated from longer segments of discharge to moving gratings. Moving gratings
      are ultimately more detectable than stationary ones, because responses to the
      former are continuously renewed. The principal characteristics of the response of
      a neuron to a stationary grating-the initial high discharge rate, which decays
      rapidly, and the change of contrast gain with time-are well captured by a model
      in which each excitatory synaptic event leads to an immediate reduction in
      synaptic gain, from which recovery is slow.

PMID- 11517286
TI  - Relaxin signalling links tyrosine phosphorylation to phosphodiesterase and
      adenylyl cyclase activity.
AB  - The relaxin receptor has so far avoided molecular cloning and characterization.
      We have therefore characterized the signalling events activated by relaxin (RLX),
      using two different cell culture-based bioassay systems: primary human
      endometrial stromal cells from the cycle (ESC) and the human monocyte cell line
      THP-1. Upon RLX stimulation, both cell types showed a rapid increase in cAMP
      accumulation, which could be inhibited by an inhibitor of G-protein activation,
      GDP-beta-S. However, evolutionarily one would expect the RLX receptor, like those
      for the structurally related hormones insulin and insulin-like growth factor-I,
      to involve tyrosine kinase activity. The specific tyrphostins AG 1478, AG 527 and
      AG 879 inhibited the RLX-stimulated cAMP response in human ESC and THP-1 cells in
      a dose-dependent manner, though the potent broad range tyrphostin AG 213 had no
      effect. Also, treatment of THP-1 cells with the potent phosphotyrosine
      phosphatase inhibitors bpV(phen) and mpV(pic) increased RLX-stimulated cAMP
      accumulation in a dose-dependent manner. The effect of the general tyrosine
      kinase inhibitor genistein (which can also inhibit some phosphodiesterases) on
      RLX-mediated cAMP accumulation strongly depended on the activity status of
      phosphodiesterase. In the absence of a phosphodiesterase inhibitor, genistein
      enhanced RLX-stimulated cAMP accumulation in both bioassays. When
      phosphodiesterase was inhibited by isobutylmethylxanthine, this effect was not
      observed. The results imply that activation of the RLX receptor uses tyrosine
      kinase signalling to control phosphodiesterase activity, and hence to up-regulate
      intracellular cAMP.

PMID- 11517287
TI  - Expression and function of the HSD-3.8 gene encoding a testis-specific protein.
AB  - The nucleotide sequence of the full length HSD-3.8 cDNA (accession number
      AF311312), encoding a human sperm component, was determined to consist of 3818 bp
      with a reading frame of 2778 bp encoding a deduced polypeptide composed of 926
      amino acids. A 0.7 kb fragment containing three immunological epitopes of HSD-3.8
      cDNA was prepared and used to construct recombinant expression vectors. The
      constructs were transformed into E.coli BL-21, and the fusion proteins were
      expressed, isolated and purified. Using the polyclonal antibodies raised against
      the purified expressed fusion proteins, positive immunostaining occurred over the
      surface of the postacrosomal zone of human spermatozoa and of germ cells within
      the seminiferous epithelium of human testis. Intense staining of large pachytene
      primary spermatocytes occurred. The capacity of the recombinant protein to reduce
      fertility as an immunogen in adult female rats was assessed. Immunized animals
      were infertile or exhibited marked reduction in their fertility. Analysis of the
      deduced HSD-3.8 polypeptide revealed the presence of a tetratricopeptide repeat
      (TPR) motif, a P-loop sequence that acts as a binding site for ATP/GTP and
      phosphorylation sites for PKC, CK2 and cAMP/cGMP-dependent protein kinases. A
      blot overlay assay with [alpha-(32)P]GTP showed that the polypeptide encoded by
      the 0.7 kb fragment of HSD-3.8 is a GTP binding protein. It was also shown to
      possess GTPase activity and to be phosphorylated by PKC in vitro. In conclusion,
      HSD-3.8 is a GTP binding protein and its activity may be regulated by
      phosphorylation.

PMID- 11517288
TI  - Effects of the ion-channel blocker quinine on human sperm volume, kinematics and
      mucus penetration, and the involvement of potassium channels.
AB  - Sperm defects in the infertile c-ros knockout mouse model have recently
      highlighted the importance of volume regulation in sperm function. In this study,
      washed human spermatozoa were shown to change size and shape, as detected by flow
      cytometry and light microscopy, in response to the ion-channel blocker quinine
      (minimum effective doses at 20 and 125 micromol/l respectively). The increase in
      sperm volume was accompanied by reduced straight-line velocity (VSL) and
      linearity (LIN) of the swim-path but increased lateral head displacement and
      curvilinear velocity, while percentage motility was unaffected. Spermatozoa in
      semen and in artificial cervical mucus were similarly affected at 0.2 and 0.5
      mmol/l quinine, resulting in marked reduction of mucus penetration and migration.
      The effects of quinine on sperm volume and kinematics were reduced or abolished
      by the K(+)-ionophores valinomycin (1 and 5 micromol/l) and gramicidin (0.5 and 1
      micromol/l). In Ca(2+)-free medium; however, the quinine effects largely
      persisted. The K(+)-channel blocker, 4-aminopyridine (1 and 4 mmol/l), mimicked
      the quinine effects in the reduction of VSL and LIN, while the K(+)-channel
      blocker, tetraethylammonium chloride (TEA, 2.5-10 mmol/l), did not affect
      kinematics. The K(+)-channel (Kv1.3)-specific inhibitor, margatoxin, and the
      Ca(2+)-dependent K(+)-channel blocker, charybdotoxin, also had no effects. This
      study suggests that volume regulation in human spermatozoa and the linear
      trajectory of their motion may rely on quinine-sensitive and TEA-insensitive,
      largely calcium-independent, potassium channels, and possibly volume-sensitive
      organic anion channels. These channels could be targets for contraception.

PMID- 11517289
TI  - The effects of antibodies to heat shock protein 70 in fertilization and embryo
      development.
AB  - The role of heat shock proteins in shielding organisms from environmental stress
      is illustrated by the large-scale synthesis of these proteins by the organisms
      studied to date. However, recent evidence also suggests an important role for
      heat shock proteins in fertilization and early development of mammalian embryos.
      We found that the presence of anti-HSP70 antibody significantly reduced tight
      binding of spermatozoa to the zona pellucida of bovine oocytes and interrupted
      completion of meiosis II and pronuclear formation. Furthermore, the presence of
      anti-HSP70 in culture medium from day 3 to day 9 of development increased
      apoptosis and significantly reduced the number of embryos reaching the blastocyst
      stage. We further observed that the proportion of apoptotic cells in bovine
      blastocysts was significantly lower after in-vitro culture with a prior exposure
      to increased temperature. However, nuclear localization of the p53 protein, which
      is thought to be essential for the up-regulation of genes involved in apoptosis
      and cell cycle arrest, was detected in the majority of nuclei in blastocysts
      exposed to increased temperature, whereas in their untreated (control)
      counterparts, p53 protein was only detected in the cytoplasm. The decrease in
      apoptosis after exposure of blastocysts to increased temperature may be
      attributed to cell cycle arrest resulting from nuclear localization of the p53
      protein and/or to an increase in heat shock protein synthesis. We propose that
      HSP70 plays a critical role in fertilization and early embryonic development.

PMID- 11517290
TI  - The use of amplified cDNA to investigate the expression of seven imprinted genes
      in human oocytes and preimplantation embryos.
AB  - Imprinted genes are characterized by expression of only one of the two alleles
      according to its inheritance from the mother or the father. This mono-allelic
      expression must arise from primary differential epigenetic modification of the
      parental alleles of the imprinted gene in the spermatozoon and the oocyte. Most
      of the information on the onset of imprinted gene expression, and on the
      molecular mechanisms regulating mono-allelic expression, have been derived from
      studies in the mouse. In this paper, we investigate the expression of seven
      imprinted genes in human preimplantation development. Due to limitations imposed
      by the rarity of human embryos available for research, our approach has been to
      screen amplified cDNA preparations prepared from human unfertilized oocytes and
      individual embryos at each of the 4-cell, 8-cell and blastocyst stages. Gene
      specific primers were used to investigate expression of the imprinted genes by
      polymerase chain reaction (PCR) analysis of these amplified cDNA. We found that
      expression is inherently variable in the amplified cDNA from embryo to embryo but
      the use of several samples at each stage showed that the SNRPN, UBE3A and PEG1
      genes are expressed throughout human preimplantation development. This was
      confirmed by direct analysis by gene-specific reverse transcription-PCR on a
      limited number of lysed embryos (one gene analysed per embryo). Thus, the
      amplified cDNA may be used to rapidly identify those imprinted genes expressed in
      preimplantation development and, hence, those genes amenable to investigation of
      the epigenetic mechanisms regulating mono-allelic expression. Confirmation of
      preimplantation expression also identifies those imprinted diseases amenable to
      preimplantation diagnosis, and the imprinted genes which may be used in
      assessment of possible perturbations of imprinting following new procedures in
      assisted reproduction. Our series of single embryo amplified cDNA are established
      as a valuable resource for comparative studies of gene expression within one
      embryo and between embryos throughout early human development. The amplified cDNA
      thus circumvent the need for a continuous supply of human embryos for studies on
      embryonic gene expression.

PMID- 11517291
TI  - Germ cell specific expression of c-kit in the human fetal gonad.
AB  - The proto-oncogene receptor, c-kit, and its ligand have been demonstrated to be
      essential to the processes of germ cell migration, proliferation and survival in
      the rodent. The aim of the present study was to investigate the expression of c
      kit mRNA and protein in human fetal ovary and testis across the gestational
      period 13-21 weeks. In the ovary, this crucial period of development spans the
      transition from oogonial replication by mitosis to primordial follicle formation.
      In the testis, germ cells (gonocytes) are mitotically active. Expression of c-kit
      mRNA was demonstrated by reverse transcription-polymerase chain reaction (RT-PCR)
      in both ovary and testis at all gestational ages examined. Testicular germ cell
      specific expression of c-kit mRNA was confirmed by RT-PCR using specific cell
      types recovered by laser capture microscopy. The expression of c-kit protein by
      both male and female germ cells was demonstrated by immunohistochemistry at all
      gestational ages examined, and was confirmed by immunoblotting. In both, c-kit
      was localized to the cell membrane except in oocytes within primordial follicles
      where it was localized to the cytoplasm. These data demonstrate that the
      expression of c-kit mRNA and protein is germ cell specific in human fetal gonads
      and are consistent with an important role for the c-kit/kit ligand signalling
      system in germ cell proliferation and survival in the developing human gonad.

PMID- 11517292
TI  - Alternatively spliced variant deleting exons 7 and 8 of the human telomerase
      reverse transcriptase gene is dominantly expressed in the uterus.
AB  - The expression level of the human telomerase reverse transcriptase (hTERT) is a
      rate-limiting determinant of telomerase activity. Several alternatively spliced
      variants of hTERT transcript are currently known. We have studied the expression
      of the splicing variants arising in the transcript encoding the reverse
      transcriptase domain, and have compared this to the telomerase activity in 27
      endometria, 14 myometria and 18 endometrial carcinomas. Telomerase activity and
      the full-length hTERT transcript were observed in endometrial samples from the
      proliferative and early secretory phases, but not in those from the late
      secretory phase. Steady-state expression of the hTERT splicing variant entirely
      lacking exon 7 and exon 8 was observed in the endometria throughout the menstrual
      cycle. In the analysed myometria, this type of splicing variant was the most
      commonly detected, and telomerase activity occurred in only three samples. In
      both endometria and myometria, the expression of the full-length transcript
      correlated well with the telomerase activity. In each of the endometrial
      carcinomas, telomerase activity was detected and the full-length transcript was
      found together with varying combinations of deletion splicing variants. These
      results suggest that regulation of splicing in the transcript encoding the hTERT
      reverse transcriptase domain is associated with telomerase activation in uterine
      tissues.

PMID- 11517293
TI  - Ectopic endometrial cells express high concentrations of interleukin (IL)-8 in
      vivo regardless of the menstrual cycle phase and respond to oestradiol by up
      regulating IL-1-induced IL-8 expression in vitro.
AB  - Endometriosis, an oestrogen-dependent disorder affecting women of reproductive
      age, is associated with active angiogenesis and an increased recruitment of
      leukocyte into the peritoneal cavity where the implants often develop. The role
      of oestrogens in the development of endometriosis has been clearly established,
      but the biochemical mechanisms of their action are still not clearly elucidated.
      The present study shows that interleukin-1 (IL-1) induces interleukin-8 (IL-8)
      secretion by endometriotic cells and that oestradiol enhances endometriotic cell
      responsiveness to IL-1. In contrast, no significant cell responsiveness to
      progesterone either alone in the culture medium or in combination with oestradiol
      was noted. Positive immunostaining for IL-8 was observed throughout endometriotic
      tissue, and no perceptible difference in the intensity of staining regarding the
      menstrual cycle phase was observed. Together with the in-vitro data, this
      suggests that IL-8 expression in endometriotic tissue is not subject to cyclic
      variation. Furthermore, this study provides evidence that oestradiol indirectly
      up-regulates the expression by ectopic endometrial cells of IL-8, a cytokine
      endowed with neutrophil chemotactic and angiogenic properties. This may
      contribute to peritoneal leukocyte recruitment and to the growth of endometriotic
      implants, and may be a new mechanism for oestradiol action in endometriosis.

PMID- 11517295
TI  - Interactions between progesterone receptor isoforms in myometrial cells in human
      labour.
AB  - Progesterone acts to maintain uterine quiescence during pregnancy. In contrast to
      many other species, no decrease in maternal serum levels of progesterone can be
      observed in humans before the onset of labour. Therefore, a 'functional'
      progesterone withdrawal in association with labour has been proposed. In humans
      the progesterone receptor (PR) exists in two isoforms, PR-A and PR-B. While PR-B
      generally mediates the effects of progesterone upon gene transcription, the role
      of PR-A during pregnancy, and in parturition, is unknown. In this study, term
      myometrium cells cultured before the onset of labour were transiently transfected
      with expression vectors for either PR-A or PR-B. Only those cells expressing PR-B
      significantly increased expression of a progesterone-sensitive reporter when
      stimulated with progesterone. Co-transfection of both isoforms of PR demonstrated
      that PR-A is a dominant repressor of transactivation in these cells. Western blot
      analysis showed that PR-A is present in human myometrium samples taken only
      after, but not before, the onset of labour. These data suggest that increased
      expression of PR-A in human myometrium may contribute to 'functional'
      progesterone withdrawal and the initiation of human labour.

PMID- 11517294
TI  - The Fas/FasL apoptotic pathway is involved in kappa-opioid-induced apoptosis of
      human endometrial stromal cells.
AB  - Human endometrium expresses specific kappa-opioid binding sites and their
      endogenous ligands, the dynorphins. In neural crest-derived tissues, kappa
      opioids affect apoptosis, a phenomenon of major significance in endometrial
      stroma physiology. Our hypothesis was that endometrial kappa-opioids may play a
      role in endometrial stromal cell apoptosis. Thus, we examined the effect of the
      synthetic kappa-opioid agonist, U69593, on the apoptotic rate of human
      endometrial stromal cells in primary culture. Apoptosis of endometrial stromal
      cells was elevated after 3 h exposure to 100 nmol/l U69593, and remained elevated
      for up to 3 days. This effect was dose-dependent and was reversed by the general
      opioid antagonist, naloxone, suggesting that it is mediated via opioid receptors.
      In parallel, semi-quantitative Western blot and flow cytometry analysis showed
      that U69593 caused a rapid but transient up-regulation of Fas protein, suggesting
      that its effect on apoptosis is mediated by activation of the Fas/FasL apoptotic
      pathway. Additionally, U69593 increased the content of the anti-apoptotic members
      of the Bcl-2 family of proteins, the Bcl-2 and Bcl-x(L), whereas it had no
      significant effect on the apoptosis-promoting homologues Bax, Bcl-x(S) and Bak.
      This implies that a transient survival mechanism is activated in stromal cells as
      a parallel rescue response to the apoptosis-inducing factor. In conclusion, our
      data suggest that endometrial opioid dynorphins may participate in the apoptotic
      processes related to endometrial tissue remodelling during early pregnancy or
      menstruation.

PMID- 11517296
TI  - Co-localization of oestrogen receptor beta and leukocyte markers in the human
      cervix.
AB  - Cervical ripening during parturition is associated with rapid production of
      catabolic enzymes by invading leukocytes and increased collagen metabolism. The
      recruitment of leukocytes is regulated by various factors including inflammatory
      mediators, prostaglandins and matrix metalloproteinases. Sex steroids may be
      indirectly or directly involved in this process. This study aimed to evaluate the
      expression of oestrogen receptor beta (ER beta) in blood cells infiltrating the
      cervix during pregnancy and parturition. Cervical biopsies were obtained from
      term pregnant, post-partal and non-pregnant women. The ER beta protein and
      leukocyte markers CD45 and CD68 were evaluated by single and double labelling
      immunohistochemistry. Quantitative values were assessed using a microscope and a
      high-resolution camera connected to a computer with image analysis program. The
      number of CD45(+) and CD68(+) cells in the cervix increased in term pregnancy and
      post-partum compared with the non-pregnant state. The ER beta antigen was co
      localized with CD45 leukocyte common antigen and CD68 macrophage specific antigen
      in blood leukocytes infiltrating the cervical tissue. The presence of ER beta in
      the cervical leukocytes suggests that oestrogen may directly regulate leukocyte
      functions in the cervix.

PMID- 11517297
TI  - Transcriptional regulation of human placental leucine aminopeptidase/oxytocinase
      gene.
AB  - Human placental leucine aminopeptidase (P-LAP) plays a major role in the
      clearance of oxytocin, which is a key hormone in regulating labour pain. To
      explore the transcriptional regulation of P-LAP gene expression in placenta, we
      performed systematic studies using human choriocarcinoma cells, BeWo and JEG-3,
      as a model of placental trophoblastic cells. Transient transfection and
      luciferase assays using various 5'-deleted P-LAP-luciferase constructs showed
      that the region from -297 to +49 of the transcription start site was responsible
      for promoter activity in these cells. Footprinting analysis with nuclear extracts
      from both cell lines demonstrated at least four sites for nucleoprotein
      interactions in this region (FP1 to FP4). Site-directed deletion of FP1-4 in
      luciferase assays indicated the significance of the FP3 region (-214 to -183) for
      high promoter activity in the cells. Electrophoretic mobility shift assays to
      identify the proteins interacting with DNA at FP3 revealed three retarded bands,
      one of which was generated by activator protein-2 (AP-2) binding. Our findings
      suggest that AP-2 may be one of the important factors regulating P-LAP gene
      expression in human placenta.

PMID- 11517298
TI  - The development of preimplantation genetic diagnosis for myotonic dystrophy using
      multiplex fluorescent polymerase chain reaction and its clinical application.
AB  - Preimplantation genetic diagnoses (PGD) for single gene defects require
      considerable time and resources for the standardization of polymerase chain
      reactions that are rapid, sensitive and reliable. Developing tests for the
      trinucleotide repeat diseases, where the expansion of unstable repeats produces
      the phenotypes, are particularly complex. One of these disorders is myotonic
      dystrophy where, at present, diagnosis at the single cell level relies on the
      detection of the normal alleles from both the affected and unaffected parent. The
      incorporation of short tandem repeat polymorphisms in the assay can give
      additional information to improve the accuracy of diagnosis. We have developed a
      multiplex fluorescent reaction for myotonic dystrophy and one of two closely
      mapped, highly heterozygous, short tandem repeats (D19S219 and D19S559) on
      chromosome 19 to reduce the possibility of misdiagnosis due to contamination, act
      as a control for allelic drop-out and maximize the number of embryos genotyped.
      This protocol was designed as a general diagnosis for myotonic dystrophy, using
      the most informative of the two polymorphisms for each couple. Subsequently this
      approach was used in a PGD treatment cycle.

PMID- 11517299
TI  - Tetracycline-inducible systems for Drosophila.
AB  - Since their inception, tetracycline (Tet)-inducible systems have become the
      method of choice for transgenic research. The Tet-Off systems have a number of
      advantages, including robust target induction using a relatively benign effector
      molecule. However, use of the Tet-On system has been fraught with difficulties,
      including high background expression in the absence of effector molecules and
      inconsistent gene induction. Recently, second generation Tet-On transactivators
      (TAs) have been described. In HeLa cells, they are far more efficient than the
      original reverse TA protein, and they exhibit lower background activity in the
      absence of effectors. Here we examine the most promising TA in transgenic
      Drosophila and characterize its in vivo properties. We report that low levels of
      doxycycline, when added to normal fly food, efficiently and rapidly induce target
      transgenes in adults, larvae, and embryos. This TA is superior to all other Tet
      On proteins, and its performance is comparable to that of the widely used Tet-Off
      TA. In addition, combining the improved Tet-On TA with the Gal4-UAS (upstream
      activating sequence) system produces robust, spatially restricted, temporally
      controlled transgene induction. Because this Tet-On TA is significantly more
      efficient than previous ones used in Drosophila, it is also possible to modulate
      gene induction by controlling the dosage of the antibiotic in the food.

PMID- 11517300
TI  - Glucagon receptor activates extracellular signal-regulated protein kinase 1/2 via
      cAMP-dependent protein kinase.
AB  - We prepared a stable cell line expressing the glucagon receptor to characterize
      the effect of G(s)-coupled receptor stimulation on extracellular signal-regulated
      protein kinase 1/2 (ERK1/2) activity. Glucagon treatment of the cell line caused
      a dose-dependent increase in cAMP concentration, activation of cAMP-dependent
      protein kinase (PKA), and transient release of intracellular calcium. Glucagon
      treatment also caused rapid dose-dependent phosphorylation and activation of
      mitogen-activated protein kinase kinase/ERK kinase (MEK1/2) and ERK1/2.
      Inhibition of either PKA or MEK1/2 blocked ERK1/2 activation by glucagon.
      However, no significant activation of several upstream activators of MEK,
      including Ras, Rap1, and Raf, was observed in response to glucagon treatment. In
      addition, chelation of intracellular calcium reduced glucagon-mediated ERK1/2
      activation. In transient transfection experiments, glucagon receptor mutants that
      bound glucagon but failed to increase intracellular cAMP and calcium
      concentrations showed no glucagon-stimulated ERK1/2 phosphorylation. We conclude
      that glucagon-induced MEK1/2 and ERK1/2 activation is mediated by PKA and that an
      increase in intracellular calcium concentration is required for maximal ERK
      activation.

PMID- 11517301
TI  - The nuclear factor kappa B (NF-kappa B): a potential therapeutic target for
      estrogen receptor negative breast cancers.
AB  - The effect of a kinase inhibitor Go6796 on growth of epidermal growth factor
      (EGF)-stimulated estrogen receptor negative (ER-) breast cancer cells in vivo and
      role of nuclear factor kappa B (NF-kappaB) on tumorogenesis have been
      investigated. This was studied in an animal model by implanting ER- mouse mammary
      epithelial tumor cells (CSMLO) in syngeneic A-J mice. (i) Local administration of
      Go6976 an inhibitor of protein kinases C alpha and beta inhibited growth of
      tumors and caused extensive necrotic degeneration and regression of the tumors
      without causing any microscopically detectable damage to the vital organs liver
      and lung. (ii) Stable expression of dominant-negative mutants of the beta subunit
      (dnIkkbeta) of the inhibitory kappa B (IkappaB) kinase (dnIkk) that selectively
      blocked activation of NF-kappaB caused loss of tumorigenic potential of CSMLO
      cells. Stable expression of dnIkkbeta also blocked phorbol 12-myristate 13
      acetate (PMA)-induced activation of NF-kappaB and overexpression of cyclin D1,
      concomitantly with the loss or reduced tumorigenic potential of these cells.
      Thus, results from in vivo and in vitro experiments strongly suggest the
      involvement of NF-kappaB in ER- mammary epithelial cell-mediated tumorigenesis.
      We propose that blocking NF-kappaB activation not only inhibits cell
      proliferation, but also antagonizes the antiapoptotic role of this transcription
      factor in ER- breast cancer cells. Thus, NF-kappaB is a potential target for
      therapy of EGFR family receptor-overexpressing ER- breast cancers.

PMID- 11517302
TI  - A monoclonal cytolytic T-lymphocyte response observed in a melanoma patient
      vaccinated with a tumor-specific antigenic peptide encoded by gene MAGE-3.
AB  - Vaccination of melanoma patients with tumor-specific antigens recognized by
      cytolytic T lymphocytes (CTL) produces significant tumor regressions in a
      minority of patients. These regressions appear to occur in the absence of massive
      CTL responses. To detect low-level responses, we resorted to antigenic
      stimulation of blood lymphocyte cultures in limiting dilution conditions,
      followed by tetramer analysis, cloning of the tetramer-positive cells, and T-cell
      receptor (TCR) sequence analysis of the CTL clones that showed strict specificity
      for the tumor antigen. A monoclonal CTL response against a MAGE-3 antigen was
      observed in a melanoma patient, who showed partial rejection of a large
      metastasis after treatment with a vaccine containing only the tumor-specific
      antigenic peptide. Tetramer analysis after in vitro restimulation indicated that
      about 1/40,000 postimmunization CD8(+) blood lymphocytes were directed against
      the antigen. The same TCR was present in all of the positive microcultures. TCR
      evaluation carried out directly on blood lymphocytes by PCR amplification led to
      a similar frequency estimate after immunization, whereas the TCR was not found
      among 2.5 x 10(6) CD8(+) lymphocytes collected before immunization. Our results
      prove unambiguously that vaccines containing only a tumor-specific antigenic
      peptide can elicit a CTL response. Even though they provide no information about
      the effector mechanisms responsible for the observed reduction in tumor mass in
      this patient, they would suggest that low-level CTL responses can initiate tumor
      rejection.

PMID- 11517303
TI  - cAMP acts as a second messenger in pollen tube growth and reorientation.
AB  - Pollen tube growth and reorientation is a prerequisite for fertilization and seed
      formation. Here we report imaging of cAMP distribution in living pollen tubes
      microinjected with the protein kinase A-derived fluorosensor. Growing tubes
      revealed a uniform distribution of cAMP with a resting concentration of
      approximately 100-150 nM. Modulators of adenylyl cyclase (AC), forskolin, and
      dideoxyadenosine could alter these values. Transient elevations in the apical
      region could be correlated with changes in the tube-growth axis, suggesting a
      role for cAMP in polarized growth. Changes in cAMP arise through the activity of
      a putative AC identified in pollen. This signaling protein shows homology to
      functional motifs in fungal AC. Expression of the cDNA in Escherichia coli
      resulted in cAMP increase and complemented a catabolic defect in the fermentation
      of carbohydrates caused by the absence of cAMP in a cyaA mutant. Antisense assays
      performed with oligodeoxynucleotide probes directed against conserved motifs
      perturbed tip growth, suggesting that modulation of cAMP concentration is vital
      for tip growth.

PMID- 11517304
TI  - Does oxidative damage to DNA increase with age?
AB  - The levels of 8-oxo-2-deoxyguanosine (oxo8dG) in DNA isolated from tissues of
      rodents (male F344 rats, male B6D2F1 mice, male C57BL/6 mice, and female C57BL/6
      mice) of various ages were measured using sodium iodide to prevent oxidative
      damage to DNA during DNA isolation. Oxo8dG was measured in nuclear DNA (nDNA)
      isolated from liver, heart, brain, kidney, skeletal muscle, and spleen and in
      mitochondrial DNA (mtDNA) isolated from liver. We observed a significant increase
      in oxo8dG levels in nDNA with age in all tissues and strains of rodents studied.
      The age-related increase in oxo8dG in nDNA from old mice was shown not to the
      result of the tissue's reduced ability to remove the oxo8dG lesion. Rather, the
      increase in oxo8dG levels appears to arise from an age-related increase in the
      sensitivity of these tissues to oxidative stress. We also observed an age-related
      increase in oxo8dG in mtDNA isolated from the livers of the rats and mice.
      Dietary restriction, which is known to retard aging and increase the lifespan of
      rodents, was shown to significantly reduce the age-related accumulation of oxo8dG
      levels in nDNA in all tissues of male B6D23F1 mice and in most tissues of male
      F344 rats. Our study also showed that dietary restriction prevented the age
      related increase in oxo8dG levels in mtDNA isolated from the livers of both rats
      and mice.

PMID- 11517305
TI  - A conformational change in the ribosomal peptidyl transferase center upon
      active/inactive transition.
AB  - The ribosome is a dynamic particle that undergoes many structural changes during
      translation. We show through chemical probing with dimethyl sulfate (DMS) that
      conformational changes occur at several nucleotides in the peptidyl transferase
      center upon alterations in pH, temperature, and monovalent ion concentration,
      consistent with observations made by Elson and coworkers over 30 years ago.
      Moreover, we have found that the pH-dependent DMS reactivity of A2451 in the
      center of the 23S rRNA peptidyl transferase region, ascribed to a perturbed pKa
      of this base, occurs only in inactive 50S and 70S ribosomes. The degree of DMS
      reactivity of this base in the inactive ribosomes depends on both the identity
      and amount of monovalent ion present. Furthermore, G2447, a residue proposed to
      be critical for the hypothesized pKa perturbation, is not essential for the
      conditional DMS reactivity at A2451. Given that the pH-dependent change in DMS
      reactivity at A2451 occurs only in inactive ribosomes, and that this DMS
      reactivity can increase with increasing salt (independently of pH), we conclude
      that this observation cannot be used as supporting evidence for a recently
      proposed model of acid/base catalyzed ribosomal transpeptidation.

PMID- 11517306
TI  - Expression and phylogeny of claudins in vertebrate primordia.
AB  - Claudins, the major transmembrane proteins of tight junctions, are members of the
      tetraspanin superfamily of proteins that mediate cellular adhesion and migration.
      Their functional importance is demonstrated by mutations in claudin genes that
      eliminate tight junctions in myelin and the testis, abolish Mg(2+) resorption in
      the kidney, and cause autosomal recessive deafness. Here we report that two
      paralogs among 15 claudin genes in the zebrafish, Danio rerio, are expressed in
      the otic and lateral-line placodes at their earliest stages of development.
      Related claudins in amphibians and mammals are expressed in a similar manner in
      vertebrate primordia such as sensory placodes, branchial arches, and limb buds.
      We also show that the claudin gene family may have expanded along the chordate
      stem lineage from urochordates to gnathostomes, in parallel with the elaboration
      of vertebrate characters. We propose that tight junctions not only form barriers
      in mature epithelia, but also participate in vertebrate morphogenesis.

PMID- 11517307
TI  - The tRNA function of SsrA contributes to controlling repression of bacteriophage
      Mu prophage.
AB  - The small regulatory RNA SsrA has both tRNA and mRNA activities. It charges
      alanine and interacts with stalled ribosomes, allowing for translation to resume
      on the SsrA mRNA moiety. Hence, unfinished peptides carry a short amino acid tag,
      which serves as a signal for degradation by energy-dependent proteases. In SsrA
      defective Escherichia coli strains, thermoinducible mutants of the transposable
      bacteriophage Mu (Mucts) are no longer induced at high temperature. Here we show
      that truncated forms of the key regulator of Mu lysogeny, the repressor Repc,
      accumulate in the absence of SsrA. These forms resemble C-terminally truncated
      dominant Mu repressor mutants previously isolated from Mucts, which are no longer
      thermoinducible and bind operator DNA with a high affinity even at high
      temperature. Using various ssrA alleles, we demonstrate the importance of SsrA
      charging on the ribosome for controlling Mu prophage repression. Our results thus
      substantiate the previous observation that trans-translation is not the only
      function of the SsrA. The alternative function of SsrA appears to influence the
      stability of Mu lysogens by controlling the translation of the C-terminal domain
      of the repressor protein, which modulates the affinity of the protein for DNA and
      its susceptibility to proteolytic degradation.

PMID- 11517308
TI  - DNA repair of a single UV photoproduct in a designed nucleosome.
AB  - Eukaryotic DNA repair enzymes must interact with the architectural hierarchy of
      chromatin. The challenge of finding damaged DNA complexed with histone proteins
      in nucleosomes is complicated by the need to maintain local chromatin structures
      involved in regulating other DNA processing events. The heterogeneity of lesions
      induced by DNA-damaging agents has led us to design homogeneously damaged
      substrates to directly compare repair of naked DNA with that of nucleosomes. Here
      we report that nucleotide excision repair in Xenopus nuclear extracts can
      effectively repair a single UV radiation photoproduct located 5 bases from the
      dyad center of a positioned nucleosome, although the nucleosome is repaired at
      about half the rate at which the naked DNA fragment is. Extract repair within the
      nucleosome is >50-fold more rapid than either enzymatic photoreversal or
      endonuclease cleavage of the lesion in vitro. Furthermore, nucleosome formation
      occurs (after repair) only on damaged naked DNA (165-bp fragments) during a 1-h
      incubation in these extracts, even in the presence of a large excess of undamaged
      DNA. This is an example of selective nucleosome assembly by Xenopus nuclear
      extracts on a short linear DNA fragment containing a DNA lesion.

PMID- 11517309
TI  - Protein docking along smooth association pathways.
AB  - We propose a docking method that mimics the way proteins bind. The method
      accounts for the dominant driving forces at the different length scales of the
      protein binding process, allowing for an efficient selection of a downhill path
      on the evolving receptor-ligand-free energy landscape. Starting from encounter
      complexes with as much as 10 A rms deviation from the native conformation, the
      method locally samples the six dimensional space of rigid-body receptor-ligand
      structures subject to a van der Waals constraint. The sampling is initially
      biased only by the desolvation and electrostatic components of the free energy,
      which capture the partial affinity of unbound structures that are more than 4 A
      away from the native state. Below this threshold, improved discrimination is
      attained by adding an increasing fraction of the van der Waals energy to the
      force field. The method, with no free parameters, was tested in eight different
      sets of independently crystallized receptor-ligand structures consistently
      predicting bound conformations with the lowest free energies and appropriate
      stability gap around 2 A from the native complex. This multistage approach is
      consistent with the underlying kinetics and internal structure of the free energy
      funnel to the bound state. Implications for the nature of the protein binding
      pathways are also discussed.

PMID- 11517311
TI  - Molecular phylogenetic analyses of the mitochondrial ADP-ATP carriers: the
      Plantae/Fungi/Metazoa trichotomy revisited.
AB  - We investigated the basal phylogeny of eukaryotes through analyses of sequences
      from the ADP-ATP mitochondrial carrier, a transmembrane protein that is stable in
      function across eukaryote kingdoms. The ADP-ATP data strongly suggest the
      grouping of Plantae and Fungi to the exclusion of Metazoa. We implemented several
      procedures to avoid pervasive analytical artifacts such as erroneous alignment,
      random rooting, long branch attraction, and misidentification of noisy
      characters. The quest of an eukaryote tree that would be largely consistent
      across multiple loci might be essentially illusory because of differential
      lineage sorting, horizontal gene transfer, and the chimeric nature of early
      eukaryotes. Better understanding of these evolutionary parameters, requiring
      separate phylogenetic analyses of multiple independent loci, is fundamental for
      resolution of the modes of emergence and evolution of the major eukaryote
      lineages.

PMID- 11517310
TI  - Caspase cleavage of MST1 promotes nuclear translocation and chromatin
      condensation.
AB  - MST1, mammalian STE20-like kinase 1, is a serine/threonine kinase that is cleaved
      and activated by caspases during apoptosis. MST1 is capable of inducing apoptotic
      morphological changes such as chromatin condensation upon overexpression. In this
      study, we show that MST1 contains two functional nuclear export signals (NESs) in
      the C-terminal domain, which is released from the N-terminal kinase domain upon
      caspase-mediated cleavage. Full-length MST1 is excluded from the nucleus and
      localized to the cytoplasm. However, either truncation of the C-terminal domain,
      point mutation of the two putative NESs, or treatment with leptomycin B, an
      inhibitor of the NES receptor, results in nuclear localization of MST1.
      Staurosporine treatment induces chromatin condensation, MST1 cleavage, and
      nuclear translocation. Staurosporine-induced chromatin condensation is partially
      inhibited by expressing a kinase-negative mutant of MST1, suggesting an important
      role of MST1 in this process. Significantly, MST1 is more efficient at inducing
      chromatin condensation when it is constitutively localized to the nucleus by
      mutation of its NESs. Moreover, inhibition of MST1 nuclear translocation by
      mutation of its cleavage sites reduces its ability to induce chromatin
      condensation. Taken together, these results suggest that truncation of the C
      terminal domain of MST1 by caspases may result in translocation of MST1 into the
      nucleus, where it promotes chromatin condensation.

PMID- 11517312
TI  - Nitroxyl anion exerts redox-sensitive positive cardiac inotropy in vivo by
      calcitonin gene-related peptide signaling.
AB  - Nitroxyl anion (NO(-)) is the one-electron reduction product of nitric oxide (NO(
      small middle dot)) and is enzymatically generated by NO synthase in vitro. The
      physiologic activity and mechanism of action of NO(-) in vivo remains unknown.
      The NO(-) generator Angeli's salt (AS, Na(2)N(2)O(3)) was administered to
      conscious chronically instrumented dogs, and pressure-dimension analysis was used
      to discriminate contractile from peripheral vascular responses. AS rapidly
      enhanced left ventricular contractility and concomitantly lowered cardiac preload
      volume and diastolic pressure (venodilation) without a change in arterial
      resistance. There were no associated changes in arterial or venous plasma cGMP.
      The inotropic response was similar despite reflex blockade with hexamethonium or
      volume reexpansion, indicating its independence from baroreflex stimulation.
      However, reflex activation did play a major role in the selective venodilation
      observed under basal conditions. These data contrasted with the pure NO donor
      diethylamine/NO, which induced a negligible inotropic response and a more
      balanced veno/arterial dilation. AS-induced positive inotropy, but not systemic
      vasodilatation, was highly redox-sensitive, being virtually inhibited by
      coinfusion of N-acetyl-l-cysteine. Cardiac inotropic signaling by NO(-) was
      mediated by calcitonin gene-related peptide (CGRP), as treatment with the
      selective CGRP-receptor antagonist CGRP(8-37) prevented this effect but not
      systemic vasodilation. Thus, NO(-) is a redox-sensitive positive inotrope with
      selective venodilator action, whose cardiac effects are mediated by CGRP-receptor
      stimulation. This fact is evidence linking NO(-) to redox-sensitive cardiac
      contractile modulation by nonadrenergic/noncholinergic peptide signaling. Given
      its cardiac and vascular properties, NO(-) may prove useful for the treatment of
      cardiovascular diseases characterized by cardiac depression and elevated venous
      filling pressures.

PMID- 11517313
TI  - Flavohemoglobin denitrosylase catalyzes the reaction of a nitroxyl equivalent
      with molecular oxygen.
AB  - We have previously reported that bacterial flavohemoglobin (HMP) catalyzes both a
      rapid reaction of heme-bound O(2) with nitric oxide (NO) to form nitrate [HMP
      Fe(II)O(2) + NO --> HMP-Fe(III) + NO(3)(-)] and, under anaerobic conditions, a
      slower reduction of heme-bound NO to an NO(-) equivalent (followed by the
      formation of N(2)O), thereby protecting against nitrosative stress under both
      aerobic and anaerobic conditions, and rationalizing our finding that NO is
      rapidly consumed across a wide range of O(2) concentrations. It has been
      alternatively suggested that HMP activity is inhibited at low pO(2) because the
      enzyme is then in the relatively inactive nitrosyl form [k(off)/k(on) for NO
      (0.000008 microM) k(off)/k(on) for O(2) (0.012 microM) and K(M) for O(2) = 30-100
      microM]. To resolve this discrepancy, we have directly measured heme-ligand
      turnover and NADH consumption under various O(2)/NO concentrations. We find that,
      at biologically relevant O(2) concentrations, HMP preferentially binds NO (not
      O(2)), which it then reacts with oxygen to form nitrate (in essence NO(-) + O(2) 
      -> NO(3)(-)). During steady-state turnover, the enzyme can be found in the ferric
      (FeIII) state. The formation of a heme-bound nitroxyl equivalent and its
      subsequent oxidation is a novel enzymatic function, and one that dominates the
      oxygenase activity under biologically relevant conditions. These data unify the
      mechanism of HMP/NO interaction with those recently described for the nematode
      Ascaris and mammalian hemoglobins, and more generally suggest that the peroxidase
      (FeIII)-like properties of globins have evolved for handling of NO.

PMID- 11517314
TI  - Cell adhesion regulates gene expression at translational checkpoints in human
      myeloid leukocytes.
AB  - Engagement of adhesion molecules on monocytes and other myeloid leukocytes, which
      are effector cells of the innate immune system, not only tethers the leukocytes
      in place but also transmits outside-in signals that induce functional changes and
      alter gene expression. We found that a subset of mRNAs that are induced or
      amplified by adhesion of human monocytes to P-selectin via its surface ligand, P
      selectin glycoprotein 1, have characteristics that suggest specialized
      translational control. One of these codes for urokinase plasminogen activator
      receptor (UPAR), a critical surface protease receptor and regulator of cell
      adhesion and migration. Although UPAR transcripts are induced by adhesion, rapid
      synthesis of the protein uses constitutive mRNA without a requirement for new
      transcription and is regulated by mammalian target of rapamycin, demonstrating
      new biologic roles for the signal-dependent translation pathway controlled by
      this intracellular kinase. The synthesis of UPAR in monocytic cells is also
      regulated by eukaryotic translation initiation factor 4E, a second key
      translational checkpoint, and phosphorylation of eukaryotic translation
      initiation factor 4E is induced by adhesion of monocytes to P-selectin.
      Translationally controlled display of UPAR by monocytes confers recognition of
      the matrix protein, vitronectin. Adhesion-dependent signaling from the plasma
      membrane to translational checkpoints represents a previously unrecognized
      mechanism for regulating surface phenotype that may be particularly important for
      myeloid leukocytes and other cells that are specialized for rapid inflammatory
      and vascular responses.

PMID- 11517316
TI  - Intragenic recombination generated two distinct Cf genes that mediate AVR9
      recognition in the natural population of Lycopersicon pimpinellifolium.
AB  - Resistance gene Cf-9 of cultivated tomato (Lycopersicon esculentum) confers
      recognition of the AVR9 elicitor protein of the fungal pathogen Cladosporium
      fulvum. The Cf-9 locus, containing Cf-9 and four homologs (Hcr9s), originates
      from Lycopersicon pimpinellifolium (Lp). We examined naturally occurring
      polymorphism in Hcr9s that confer AVR9 recognition in the Lp population. AVR9
      recognition occurs frequently throughout this population. In addition to Cf-9, we
      discovered a second gene in Lp, designated 9DC, which also confers AVR9
      recognition. Compared with Cf-9, 9DC is more polymorphic, occurs more frequently,
      and is more widely spread throughout the Lp population, suggesting that 9DC is
      older than Cf-9. The sequences of Cf-9 and 9DC suggest that Cf-9 evolved from 9DC
      by intragenic recombination between 9DC and another Hcr9. The fact that the 9DC
      and Cf-9 proteins differ in 61 aa residues, and both mediate recognition of AVR9,
      shows that in nature Hcr9 proteins with the same recognitional specificity can
      vary significantly.

PMID- 11517315
TI  - A cell-based system that recapitulates the dynamic light-dependent regulation of
      the vertebrate clock.
AB  - The primary hallmark of circadian clocks is their ability to entrain to
      environmental stimuli. The dominant, and therefore most physiologically
      important, entraining stimulus comes from environmental light cycles. Here we
      describe the establishment and characterization of a new cell line, designated
      Z3, which derives from zebrafish embryos and contains an independent, light
      entrainable circadian oscillator. Using this system, we show distinct and
      differential light-dependent gene activation for several central clock
      components. In particular, activation of Per2 expression is shown to be strictly
      regulated and dependent on light. Furthermore, we demonstrate that Per1, Per2,
      and Per3 all have distinct responses to light-dark (LD) cycles and light-pulse
      treatments. We also show that Clock, Bmal1, and Bmal2 all oscillate under LD and
      dark-dark conditions with similar kinetics, but only Clock is significantly
      induced while initiating a light-induced circadian oscillation in Z3 cells that
      have never been exposed to a LD cycle. Finally, our results suggest that Per2 is
      responsible for establishing the phase of a circadian rhythm entraining to an
      alternate LD cycle. These findings not only underscore the complexity by which
      central clock genes are regulated, but also establishes the Z3 cells as an
      invaluable system for investigating the links between light-dependent gene
      activation and the signaling pathways responsible for vertebrate circadian
      rhythms.

PMID- 11517317
TI  - Characterization of key residues in the subdomain encoded by exons 8 and 9 of
      human inducible nitric oxide synthase: a critical role for Asp-280 in substrate
      binding and subunit interactions.
AB  - Human inducible nitric oxide synthase (iNOS) is active as a dimer of two
      identical subunits. Each subunit has an amino-terminal oxygenase domain that
      binds the substrate l-Arg and the cofactors heme and tetrahydrobiopterin and a
      carboxyl-terminal reductase domain that binds FMN, FAD, and NADPH. We previously
      demonstrated that a subdomain in the oxygenase domain encoded by exons 8 and 9 is
      important for dimer formation and NO synthesis. Further, we identified Trp-260,
      Asn-261, Tyr-267, and Asp-280 as key residues in that subdomain. In this study,
      using an Escherichia coli expression system, we produced, purified, and
      characterized wild-type iNOS and iNOS-Ala mutants. Using H(2)O(2)-supported
      oxidation of N(omega)-hydroxy-l-Arg, we demonstrate that the iNOS mutants'
      inabilities to synthesize NO are due to selective defects in the oxygenase domain
      activity. Detailed characterization of the Asp-280-Ala mutant revealed that it
      retains a functional reductase domain, as measured by its ability to reduce
      cytochrome c. Gel permeation chromatography confirmed that the Asp-280-Ala mutant
      exists as a dimer, but, in contrast to wild-type iNOS, urea-generated monomers of
      the mutant fail to reassociate into dimers when incubated with l-Arg and
      tetrahydrobiopterin, suggesting inadequate subunit interaction. Spectral analysis
      reveals that the Asp-280-Ala mutant does not bind l-Arg. This indicates that, in
      addition to dimerization, proper subunit interaction is required for substrate
      binding. These data, by defining a critical role for Asp-280 in substrate binding
      and subunit interactions, give insights into the mechanisms of regulation of iNOS
      activity.

PMID- 11517319
TI  - The coreceptor mutation CCR5Delta32 influences the dynamics of HIV epidemics and
      is selected for by HIV.
AB  - We explore the impact of a host genetic factor on heterosexual HIV epidemics by
      using a deterministic mathematical model. A protective allele unequally
      distributed across populations is exemplified in our models by the 32-bp deletion
      in the host-cell chemokine receptor CCR5, CCR5Delta32. Individuals homozygous for
      CCR5Delta32 are protected against HIV infection whereas those heterozygous for
      CCR5Delta32 have lower pre-AIDS viral loads and delayed progression to AIDS.
      CCR5Delta32 may limit HIV spread by decreasing the probability of both risk of
      infection and infectiousness. In this work, we characterize epidemic HIV within
      three dynamic subpopulations: CCR5/CCR5 (homozygous, wild type), CCR5/CCR5Delta32
      (heterozygous), and CCR5Delta32/CCR5Delta32 (homozygous, mutant). Our results
      indicate that prevalence of HIV/AIDS is greater in populations lacking the
      CCR5Delta32 alleles (homozygous wild types only) as compared with populations
      that include people heterozygous or homozygous for CCR5Delta32. Also, we show
      that HIV can provide selective pressure for CCR5Delta32, increasing the frequency
      of this allele.

PMID- 11517318
TI  - Accelerated regulatory gene evolution in an adaptive radiation.
AB  - The disparity between rates of morphological and molecular evolution remains a
      key paradox in evolutionary genetics. A proposed resolution to this paradox has
      been the conjecture that morphological evolution proceeds via diversification in
      regulatory loci, and that phenotypic evolution may correlate better with
      regulatory gene divergence. This conjecture can be tested by examining rates of
      regulatory gene evolution in species that display rapid morphological
      diversification within adaptive radiations. We have isolated homologues to the
      Arabidopsis APETALA3 (ASAP3/TM6) and APETALA1 (ASAP1) floral regulatory genes and
      the CHLOROPHYLL A/B BINDING PROTEIN9 (ASCAB9) photosynthetic structural gene from
      species in the Hawaiian silversword alliance, a premier example of plant adaptive
      radiation. We have compared rates of regulatory and structural gene evolution in
      the Hawaiian species to those in related species of North American tarweeds.
      Molecular evolutionary analyses indicate significant increases in nonsynonymous
      relative to synonymous nucleotide substitution rates in the ASAP3/TM6 and ASAP1
      regulatory genes in the rapidly evolving Hawaiian species. By contrast, no
      general increase is evident in neutral mutation rates for these loci in the
      Hawaiian species. An increase in nonsynonymous relative to synonymous nucleotide
      substitution rate is also evident in the ASCAB9 structural gene in the Hawaiian
      species, but not to the extent displayed in the regulatory loci. The
      significantly accelerated rates of regulatory gene evolution in the Hawaiian
      species may reflect the influence of allopolyploidy or of selection and adaptive
      divergence. The analyses suggest that accelerated rates of regulatory gene
      evolution may accompany rapid morphological diversification in adaptive
      radiations.

PMID- 11517320
TI  - Pronounced climatic variations in Alaska during the last two millennia.
AB  - Paired oxygen-isotopic analyses of abiotic carbonate and benthic-ostracode shells
      from lake sediments provide a continuous quantitative record of growing-season
      temperature for the past 2000 years in the northwestern foothills of the Alaska
      Range. This record reveals three time intervals of comparable warmth: anno Domini
      (A.D.) 0-300, 850-1200, and post-1800, the latter two of which correspond to the
      Medieval Climatic Anomaly and climatic amelioration after the end of the Little
      Ice Age. The Little Ice Age culminated at A.D. 1700, when the climate was
      approximately 1.7 degrees C colder than at present. A marked climatic cooling
      also occurred around A.D. 600, coinciding with extensive glacial advances in
      Alaska. Comparisons of this temperature record with ostracode trace-element
      ratios (Mg/Ca, Sr/Ca) further suggest that colder periods were wetter and vice
      versa during the past 2000 years.

PMID- 11517321
TI  - The principle of delivery of T cell epitopes to antigen-presenting cells applied
      to peptides from influenza virus, ovalbumin, and hen egg lysozyme: implications
      for peptide vaccination.
AB  - Targeting of antigens to antigen-presenting cells (APCs) increases CD4(+) T cell
      activation, and this observation can be exploited in the development of new
      vaccines. We have chosen an antigen-targeting approach in which we make
      recombinant antibodies (Abs) with T cell epitopes in their constant region and
      APC-specific variable regions. Three commonly used model epitopes, amino acids
      110-120 of hemagglutinin, 323-339 of ovalbumin, and 46-61 of hen egg lysozyme,
      were introduced as loops in the C(H)1 domain of human IgG3. For all three
      epitopes, we show that the recombinant molecules are secreted from transfected
      cells. The epitopes are presented to specific T cells, and targeting to IgD on B
      cells in vitro enhances the presentation efficiency by 10(4) to 10(5) compared
      with the free peptide. After i.v. injection, the epitopes targeted to IgD are
      presented by splenic APCs to activate specific T cells, whereas little or no
      activation could be detected without targeting, even after the amount of antigen
      injected was increased 100-fold or more. Because a wide variety of T cell
      epitopes, in terms of both length and secondary structure, can be tolerated in
      loops in constant domains of Abs, the Ab constant region seems to have the
      intrinsic stability that is needed for this fusion molecule strategy. It might
      thus be possible to load the Ab with several different epitopes in loops in
      different domains and thereby make a targeted multisubunit vaccine.

PMID- 11517322
TI  - Glutamate-induced transient modification of the postsynaptic density.
AB  - Depolarization of rat hippocampal neurons with a high concentration of external
      potassium induces a thickening of postsynaptic densities (PSDs) within 1.5-3 min.
      After high-potassium treatment, PSDs thicken 2.1-fold in cultured neurons and 1.4
      fold in hippocampal slices compared with their respective controls. Thin-section
      immunoelectron microscopy of hippocampal cultures indicates that at least part of
      the observed thickening of PSDs can be accounted for by an accumulation of
      Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) on their cytoplasmic
      faces. Indeed, PSD-associated gold label for CaMKII increases 5-fold after
      depolarization with potassium. The effects of high-potassium treatment on the
      composition and structure of the PSDs are mimicked by direct application of
      glutamate. In cultures, glutamate-induced thickening of PSDs and the accumulation
      of CaMKII on PSDs are reversed within 5 min of removal of glutamate and Ca(2+)
      from the extracellular medium. These results suggest that PSDs are dynamic
      structures whose thickness and composition are subject to rapid and transient
      changes during synaptic activity.

PMID- 11517323
TI  - Heterosynaptic metaplasticity in the hippocampus in vivo: a BCM-like modifiable
      threshold for LTP.
AB  - The homeostatic maintenance of the "modification threshold" for inducing long
      term potentiation (LTP) is a fundamental feature of the Bienenstock, Cooper, and
      Munro (BCM) model of synaptic plasticity. In the present study, two key features
      of the modification threshold, its heterosynaptic expression and its regulation
      by postsynaptic neural activity, were tested experimentally in the dentate gyrus
      of awake, freely moving rats. Conditioning stimulation ranging from 10 to 1,440
      brief 400-Hz trains, when applied to medial perforant path afferents, raised the
      threshold for LTP induction heterosynaptically in the neighboring lateral
      perforant path synapses. This effect recovered slowly over a 7- to 35-day period.
      The same conditioning paradigms, however, did not affect the reversal of long
      term depression. The inhibition of LTP by medial-path conditioning stimulation
      was N-methyl-D-aspartate (NMDA) receptor-dependent, but antidromic stimulation of
      the granule cells could also inhibit lateral path LTP induction, independently of
      NMDA receptor activation. Increased calcium buffering is a potential mechanism
      underlying the altered LTP threshold, but the levels of two important calcium
      binding proteins did not increase after conditioning stimulation, nor was de novo
      protein synthesis required for generating the threshold shift. These data
      confirm, in an in vivo model, two key postulates of the BCM model regarding the
      LTP threshold. They also provide further evidence for the broad sensitivity of
      synaptic plasticity mechanisms to the history of prior activity, i.e.,
      metaplasticity.

PMID- 11517324
TI  - Electrostatics of nanosystems: application to microtubules and the ribosome.
AB  - Evaluation of the electrostatic properties of biomolecules has become a standard
      practice in molecular biophysics. Foremost among the models used to elucidate the
      electrostatic potential is the Poisson-Boltzmann equation; however, existing
      methods for solving this equation have limited the scope of accurate
      electrostatic calculations to relatively small biomolecular systems. Here we
      present the application of numerical methods to enable the trivially parallel
      solution of the Poisson-Boltzmann equation for supramolecular structures that are
      orders of magnitude larger in size. As a demonstration of this methodology,
      electrostatic potentials have been calculated for large microtubule and ribosome
      structures. The results point to the likely role of electrostatics in a variety
      of activities of these structures.

PMID- 11517325
TI  - Activation of beta-major globin gene transcription is associated with recruitment
      of NF-E2 to the beta-globin LCR and gene promoter.
AB  - The mouse beta-globin gene locus control region (LCR), located upstream of the
      beta-globin gene cluster, is essential for the activated transcription of genes
      in the cluster. The LCR contains multiple binding sites for transactivators,
      including Maf-recognition elements (MAREs). However, little is known about the
      specific proteins that bind to these sites or the time at which they bind during
      erythroid differentiation. We have performed chromatin immunoprecipitation
      experiments to determine the recruitment of the erythroid-specific transactivator
      p45 NF-E2/MafK (p18 NF-E2) heterodimer and small Maf proteins to various regions
      in the globin gene locus before and after the induction of murine erythroleukemia
      (MEL) cell differentiation. We report that, before induction, the LCR is occupied
      by small Maf proteins, and, on erythroid maturation, the NF-E2 complex is
      recruited to the LCR and the active globin promoters, even though the promoters
      do not contain MAREs. This differentiation-coupled recruitment of NF-E2 complex
      correlates with a greater than 100-fold increase in beta-major globin
      transcription, but is not associated with a significant change in locus-wide
      histone H3 acetylation. These findings suggest that the beta-globin gene locus
      exists in a constitutively open chromatin conformation before terminal
      differentiation, and we speculate that recruitment of NF-E2 complex to the LCR
      and active promoters may be a rate-limiting step in the activation of beta-globin
      gene expression.

PMID- 11517326
TI  - The US3 protein kinase of herpes simplex virus 1 mediates the posttranslational
      modification of BAD and prevents BAD-induced programmed cell death in the absence
      of other viral proteins.
AB  - Earlier studies have shown that the d120 mutant of herpes simplex virus 1, which
      lacks both copies of the alpha4 gene, induces apoptosis in all cell lines tested.
      In some cell lines d120-induced apoptosis, manifested by the release of
      cytochrome c, activation of caspase 3, and fragmentation of cellular DNA, is
      blocked by the overexpression of Bcl-2. In these cells viral protein kinase U(S)3
      delivered in trans blocks apoptosis induced by the mutant virus at a
      premitochondrial stage. We report that the U(S)3 protein kinase targets the pro
      apoptotic BAD member of the Bcl-2 family. Specifically, the U(S)3 protein kinase
      mediates a posttranslational modification of BAD and blocks its cleavage, which
      is reported to activate apoptosis. Thus, U(S)3 protein kinase is the sole viral
      protein required to block activation of caspase 3, prevent cleavage of poly(ADP
      ribose) polymerase, and block fragmentation of cellular DNA induced by BAD.

PMID- 11517327
TI  - Cloning and characterization of PIMT, a protein with a methyltransferase domain,
      which interacts with and enhances nuclear receptor coactivator PRIP function.
AB  - The nuclear receptor coactivators participate in the transcriptional activation
      of specific genes by nuclear receptors. In this study, we report the isolation of
      a nuclear receptor coactivator-interacting protein from a human liver cDNA
      library by using the coactivator peroxisome proliferator-activated receptor
      interacting protein (PRIP) (ASC2/AIB3/RAP250/NRC/TRBP) as bait in a yeast two
      hybrid screen. Human PRIP-interacting protein cDNA has an ORF of 2,556
      nucleotides, encodes a protein with 852 amino acids, and contains a 9-aa
      VVDAFCGVG methyltransferase motif I and an invariant GXXGXXI segment found in K
      homology motifs of many RNA-binding proteins. The gene encoding this protein,
      designated PRIP-interacting protein with methyltransferase domain (PIMT), is
      localized on chromosome 8q11 and spans more than 40 kb. PIMT mRNA is ubiquitously
      expressed, with a high level of expression in heart, skeletal muscle, kidney,
      liver, and placenta. Using the immunofluorescence localization method, we found
      that PIMT and PRIP proteins appear colocalized in the nucleus. PIMT strongly
      interacts with PRIP under in vitro and in vivo conditions, and the PIMT-binding
      site on PRIP is in the region encompassing amino acids 773-927. PIMT binds S
      adenosyl-l-methionine, the methyl donor for methyltransfer reaction, and it also
      binds RNA, suggesting that it is a putative RNA methyltransferase. PIMT enhances
      the transcriptional activity of peroxisome proliferator-activated receptor gamma
      and retinoid-X-receptor alpha, which is further stimulated by coexpression of
      PRIP, implying that PIMT is a component of nuclear receptor signal transduction
      apparatus acting through PRIP. Definitive identification of the specific
      substrate of PIMT and the role of this RNA-binding protein in transcriptional
      regulation remain to be determined.

PMID- 11517328
TI  - Human DNA replication initiation factors, ORC and MCM, associate with oriP of
      Epstein-Barr virus.
AB  - The 165-kb chromosome of Epstein-Barr virus (EBV) is replicated by cellular
      enzymes only once per cell cycle in human cells that are latently infected. Here,
      we report that the human origin recognition complex, ORC, can be detected in
      association with an EBV replication origin, oriP, in cells by using antibodies
      against three different subunits of human ORC to precipitate crosslinked
      chromatin. Mcm2, a subunit of the MCM replication licensing complex, was found to
      associate with oriP during G(1) and to dissociate from it during S phase. The
      detection of ORC and Mcm2 at oriP was shown to require the presence of the 120-bp
      replicator of oriP. Licensing and initiation of replication at oriP of EBV thus
      seem to be mediated by ORC. This is an example of a virus apparently using ORC
      and associated factors for the propagation of its genome.

PMID- 11517329
TI  - Discrepancy between ELISPOT IFN-gamma secretion and binding of A2/peptide
      multimers to TCR reveals interclonal dissociation of CTL effector function from
      TCR-peptide/MHC complexes half-life.
AB  - Activation of CD8(+) cytolytic T lymphocytes (CTLs) by antigen is triggered by
      the interaction of clonotypic alphabeta T cell receptors (TCRs) with antigenic
      peptides bound to MHC class I molecules (pMHC complexes). Fluorescent multimeric
      pMHC complexes have been shown to specifically stain antigen-specific CTLs by
      directly binding the TCR. In tumor-infiltrating lymphocytes from a melanoma
      patient we found a high frequency of tyrosinase(368-376) peptide-specific cells
      as detected by IFN-gamma ELISPOT, without detectable staining with the
      corresponding A2/peptide multimers. Surprisingly, these T cells were able to lyse
      tyrosinase(368-376) peptide-pulsed target cells as efficiently as other specific
      T cells that were stained by multimers. Analysis of the staining patterns under
      different conditions of incubation time and temperature revealed that these
      results were explained by major differences in TCR-multimeric ligand interaction
      kinetics among the clones. Whereas no direct quantitative correlation between
      antigenic peptide concentration required for CTL effector functions and
      equilibrium multimer binding was observed interclonally, the latter was
      profoundly affected by the kinetics of TCR-ligand interaction. More importantly,
      our data indicate that similar levels of T cell activation can be achieved by
      independent CD8(+) T cell clonotypes displaying different TCR/pMHC complex
      dissociation rates.

PMID- 11517330
TI  - Antibody targeting studies in a transgenic murine model of spontaneous colorectal
      tumors.
AB  - Monoclonal antibodies (mAbs) have been used to treat malignancies in humans with
      varying degrees of success. Progress has been hindered by the lack of suitable
      animal models, which would ideally consist of immunocompetent animals that are
      tolerant to tumor-associated antigens. Suitable models would allow the study and
      optimization of anti-tumor immunotherapy. We describe a murine model for the
      study of immunotherapy in colorectal cancers. Carcinoembryonic antigen (CEA) is a
      cell-surface glycoprotein that is expressed on normal human intestinal epithelium
      and that is overexpressed in intestinal tumors. Mice that are transgenic for the
      human CEA gene (CEA.Tg) were crossed with multiple intestinal neoplasia (MIN)
      mice. MIN mice carry a germline APC mutation and are prone to the development of
      intestinal adenomas. The offspring from the MIN x CEA.Tg cross developed
      intestinal adenomas that were shown by immunohistochemistry to overexpress CEA.
      Pharmacokinetic studies by using (125)I-labeled anti-CEA mAb PR1A3 showed rapid
      localization of antibody to tissues expressing CEA, especially the
      gastrointestinal tract. Macroscopic and microscopic radioautographic analysis of
      the gastrointestinal tracts from MIN/CEA.Tg mice indicated that PR1A3 targeted
      and was retained in tumors at levels higher than in areas of normal gut. These
      results demonstrate the utility of the MIN/CEA.Tg mouse as a model for the study
      of anti-CEA immunotherapy and, furthermore, demonstrate the efficiency of tumor
      localization by PR1A3.

PMID- 11517331
TI  - Transportin-SR2 mediates nuclear import of phosphorylated SR proteins.
AB  - Serine/arginine-rich proteins (SR proteins) are a family of nuclear factors that
      play important roles in both constitutive and regulated precursor mRNA splicing.
      The domain rich in arginine/serine (RS) repeats (RS domain) serves as both a
      nuclear and subnuclear localization signal. We previously identified an importin
      beta family protein, transportin-SR2 (TRN-SR2), that specifically interacts with
      phosphorylated RS domains. A TRN-SR2 mutant deficient in Ran binding colocalizes
      with SR proteins in nuclear speckles, suggesting a role of TRN-SR2 in nuclear
      targeting of SR proteins. Using in vitro import assays, we here show that nuclear
      import of SR protein fusions requires cytosolic factors, and that the RS domain
      becomes phosphorylated in the import reaction. Reconstitution of SR protein
      import by using recombinant transport factors clearly demonstrates that TRN-SR2
      is capable of targeting phosphorylated, but not unphosphorylated, SR proteins to
      the nucleus. Therefore, RS domain phosphorylation is critical for TRN-SR2
      mediated nuclear import. Interestingly, we found that the RNA-binding activity of
      SR proteins confers temperature sensitivity to their nuclear import. Finally, we
      show that TRN-SR2 interacts with a nucleoporin and is targeted not only to the
      nuclear envelope but also to nuclear speckles in vitro. Thus, TRN-SR2 may perhaps
      escort SR protein cargoes to nuclear subdomains.

PMID- 11517332
TI  - Induction of stereotypy in dopamine-deficient mice requires striatal D1 receptor
      activation.
AB  - Motor stereotypies are abnormally repetitive behaviors that can develop with
      excessive dopaminergic stimulation and are features of some neurologic disorders.
      To investigate the mechanisms required for the induction of stereotypy, we
      examined the responses of dopamine-deficient (DD) mice to increasing doses of the
      dopamine precursor L-DOPA. DD mice lack the ability to synthesize dopamine (DA)
      specifically in dopaminergic neurons yet exhibit robust hyperlocomotion relative
      to wild-type (WT) mice when treated with L-DOPA, which restores striatal DA
      tissue content to approximately 10% of WT levels. To further elevate brain DA
      content in DD mice, we administered the peripheral L-amino acid decarboxylase
      inhibitor carbidopa along with L-DOPA (C/l-DOPA). When striatal DA levels reached
      >50% of WT levels, a transition from hyperlocomotion to intense, focused
      stereotypy was observed that was correlated with an induction of c-fos mRNA in
      the ventrolateral and central striatum as well as the somatosensory cortex. WT
      mice were unaffected by C/L-DOPA treatments. A D1, but not a D2, receptor
      antagonist attenuated both the C/L-DOPA-induced stereotypy and the c-fos
      induction. Consistent with these results, stereotypy could be induced in DD mice
      by a D1, but not by a D2, receptor agonist, with neither agonist inducing
      stereotypy in WT mice. Intrastriatal injection of a D1 receptor antagonist
      ameliorated the stereotypy and c-fos induction by C/L-DOPA. These results
      indicate that activation of D1 receptors on a specific population of striatal
      neurons is required for the induction of stereotypy in DD mice.

PMID- 11517333
TI  - Plastic neural changes and reading improvement caused by audiovisual training in
      reading-impaired children.
AB  - This study aimed at determining whether audiovisual training without linguistic
      material has a remediating effect on reading skills and central auditory
      processing in dyslexic children. It was found that this training resulted in
      plastic changes in the auditory cortex, indexed by enhanced electrophysiological
      mismatch negativity and faster reaction times to sound changes. Importantly,
      these changes were accompanied by improvement in reading skills. The results
      indicate that reading difficulties can be ameliorated by special training
      programs and, further, that the training effects can be observed in brain
      activity. Moreover, the fact that the present training effects were obtained by
      using a program including no linguistic material indicates that dyslexia is at
      least partly based on a general auditory perceptual deficit.

PMID- 11517335
TI  - Immune hyporesponsiveness to amyloid beta-peptide in amyloid precursor protein
      transgenic mice: implications for the pathogenesis and treatment of Alzheimer's
      disease.
AB  - Alzheimer's disease is a dementia that involves progressive deposition of amyloid
      beta-protein (Abeta) in brain regions important for memory and cognition,
      followed by secondary inflammation that contributes to the neuropathologic
      process. Immunization with Abeta can reduce cerebral Abeta burden and consequent
      neuropathologic changes in the brains of mice transgenic for the beta-amyloid
      precursor protein (APP). We found that transgenic expression of human APP in
      B6SJL mice, under the prion promoter, results in immune hyporesponsiveness to
      human Abeta, in terms of both antibody and cellular immune responses. The
      decreased antibody responses were related not to B cell tolerance but rather to
      the inability of Abeta-specific T cells to provide help for antibody production.
      The immune hyporesponsiveness could be overcome if T cell help was provided by
      coupling an Abeta B cell epitope to BSA. Our results suggest that expression of
      APP in transgenic mice is associated with an Abeta-specific impaired adaptive
      immune response that may contribute to the neuropathology. Moreover, humans with
      life-long elevation of brain and peripheral Abeta (e.g., patients with presenilin
      mutations or Down syndrome) could have reduced immune responses to Abeta
      vaccination.

PMID- 11517334
TI  - Control of Drosophila perineurial glial growth by interacting neurotransmitter
      mediated signaling pathways.
AB  - Drosophila peripheral nerves, similar structurally to the peripheral nerves of
      mammals, comprise a layer of axons and inner glia, surrounded by an outer
      perineurial glial layer. Although it is well established that intercellular
      communication occurs among cells within peripheral nerves, the signaling pathways
      used and the effects of this signaling on nerve structure and function remain
      incompletely understood. Here we demonstrate with genetic methods that the
      Drosophila peripheral nerve is a favorable system for the study of intercellular
      signaling. We show that growth of the perineurial glia is controlled by
      interactions among five genes: ine, which encodes a putative neurotransmitter
      transporter; eag, which encodes a potassium channel; push, which encodes a large,
      Zn(2+)-finger-containing protein; amn, which encodes a putative neuropeptide
      related to the pituitary adenylate cyclase activator peptide; and NF1, the
      Drosophila ortholog of the human gene responsible for type 1 neurofibromatosis.
      In other Drosophila systems, push and NF1 are required for signaling pathways
      mediated by Amn or the pituitary adenylate cyclase activator peptide. Our results
      support a model in which the Amn neuropeptide, acting through Push and NF1,
      inhibits perineurial glial growth, whereas the substrate neurotransmitter of Ine
      promotes perineurial glial growth. Defective intercellular signaling within
      peripheral nerves might underlie the formation of neurofibromas, the hallmark of
      neurofibromatosis.

PMID- 11517336
TI  - Interaction between growth arrest-DNA damage protein 34 and Src kinase Lyn
      negatively regulates genotoxic apoptosis.
AB  - Genotoxic stresses activate intracellular signaling molecules, which lead to
      growth arrest, DNA repair, and/or apoptosis. Among these molecules are the growth
      arrest and DNA damage protein 34 (GADD34) and the Src-related protein tyrosine
      kinase Lyn. Here, we report that these two proteins physically and functionally
      interact to regulate DNA damage-induced apoptosis. Multiple isolates of GADD34
      and the related murine protein MyD116 were identified as binding partners of Lyn
      in a yeast two-hybrid screen. The specific interaction was confirmed by in vitro
      association of GADD34 with glutathione S-transferase fusion proteins containing
      the Src Homology 3 (SH3) domain of Lyn, as well as coimmunoprecipitation of
      GADD34 and Lyn from mammalian cells. GADD34 was tyrosine-phosphorylated in vivo
      in a Lyn-dependent manner. Lyn efficiently phosphorylated affinity-purified
      GADD34 in vitro. Lyn negatively regulated the proapoptotic function of GADD34 in
      a kinase-dependent manner. Expression of wild-type, but not kinase-inactive, Lyn
      weakened promotion of apoptosis by GADD34 following treatment with methyl
      methanesulfonate or ionizing radiation in HEK293 and HeLa cells. In contrast,
      pretreatment of cells with the Src-specific tyrosine kinase inhibitor PP1
      strengthened promotion of apoptosis by GADD34. We propose that Lyn regulates the
      proapoptotic function of GADD34 by binding and phosphorylating it.

PMID- 11517337
TI  - Telomerase reverse transcriptase promotes cardiac muscle cell proliferation,
      hypertrophy, and survival.
AB  - Cardiac muscle regeneration after injury is limited by "irreversible" cell cycle
      exit. Telomere shortening is one postulated basis for replicative senescence, via
      down-regulation of telomerase reverse transcriptase (TERT); telomere dysfunction
      also is associated with greater sensitivity to apoptosis. Forced expression of
      TERT in cardiac muscle in mice was sufficient to rescue telomerase activity and
      telomere length. Initially, the ventricle was hypercellular, with increased
      myocyte density and DNA synthesis. By 12 wk, cell cycling subsided; instead, cell
      enlargement (hypertrophy) was seen, without fibrosis or impaired function.
      Likewise, viral delivery of TERT was sufficient for hypertrophy in cultured
      cardiac myocytes. The TERT virus and transgene also conferred protection from
      apoptosis, in vitro and in vivo. Hyperplasia, hypertrophy, and survival all
      required active TERT and were not seen with a catalytically inactive mutation.
      Thus, TERT can delay cell cycle exit in cardiac muscle, induce hypertrophy in
      postmitotic cells, and promote cardiac myocyte survival.

PMID- 11517338
TI  - Furin inhibition results in absent or decreased invasiveness and tumorigenicity
      of human cancer cells.
AB  - Pro-protein convertases such as furin are expressed in many human tumor lines and
      primary tumors. Furin processes stromelysin-3, membrane type 1 matrix
      metalloproteinase (MMPs) involved in tumor cell invasiveness, as well as growth
      factors such as transforming growth factor beta1. Evaluation of furin expression
      in head and neck squamous cell carcinoma (HNSCC) cells exhibiting different
      invasive ability showed that furin overexpression correlated with their
      respective invasiveness. The use of a selective furin inhibitor, alpha 1-PDX
      (PDX) was studied in three furin-expressing invasive HNSCC cell lines. The
      effects of PDX transfection were evaluated in vivo and in vitro to determine
      changes in the malignant phenotype. Transfection of HNSCC cell lines with PDX
      resulted in significant decrease or absence of tumorigenicity after s.c.
      inoculation into severe combined immunodeficient mice. Likewise, in vitro
      invasiveness was reduced approximately 50%. The in vivo invasion assay using
      tracheal xenotransplants showed even more drastic reductions of the invasive
      ability of PDX-transfected cells (up to an 80% decrease). PDX-transfected cells
      did not invade or penetrated less into the tracheal wall tissues than their
      vector alone-transfected counterparts. In addition, the former cells showed a
      remarkable decrease in MMP-2 processing and activity. After PDX transfection the
      cells were less efficient in processing the tumor progression-associated furin
      substrates transforming growth factor beta1 and pro-membrane type 1-MMP. These
      findings indicate that furin inhibition is a feasible approach to attenuate and
      even abolish certain critical attributes of the advanced malignant phenotype.
      Thus, furin should be considered as a promising target for cancer therapy.

PMID- 11517339
TI  - Investigating stem cells in human colon by using methylation patterns.
AB  - The stem cells that maintain human colon crypts are poorly characterized. To
      better determine stem cell numbers and how they divide, epigenetic patterns were
      used as cell fate markers. Methylation exhibits somatic inheritance and random
      changes that potentially record lifelong stem cell division histories as binary
      strings or tags in adjacent CpG sites. Methylation tag contents of individual
      crypts were sampled with bisulfite sequencing at three presumably neutral loci.
      Methylation increased with aging but varied between crypts and was mosaic within
      single crypts. Some crypts appeared to be quasi-clonal as they contained more
      unique tags than expected if crypts were maintained by single immortal stem
      cells. The complex epigenetic patterns were more consistent with a crypt niche
      model wherein multiple stem cells were present and replaced through periodic
      symmetric divisions. Methylation tags provide evidence that normal human crypts
      are long-lived, accumulate random methylation errors, and contain multiple stem
      cells that go through "bottlenecks" during life.

PMID- 11517340
TI  - An acquired and a native penicillin-binding protein cooperate in building the
      cell wall of drug-resistant staphylococci.
AB  - The blanket resistance of methicillin-resistant Staphylococcus aureus to all beta
      lactam antibiotics--which had such a devastating impact on chemotherapy of
      staphylococcal infections--is related to the properties of the key component of
      this resistance mechanism: the "acquired" penicillin-binding protein (PBP)-2A,
      which has unusual low affinity for all beta-lactam antibiotics. Until now, the
      accepted model of resistance implied that in the presence of beta-lactam
      antibiotics in the surrounding medium, PBP2A must take over the biosynthesis of
      staphylococcal cell wall from the four native staphylococcal PBPs because the
      latter become rapidly acylated and inactivated at even low concentrations of the
      antibiotic. However, recent observations indicate that this model requires
      revision. Inactivation of the transglycosylase domain, but not the transpeptidase
      domain, of PBP2 of S. aureus prevents expression of beta-lactam resistance,
      despite the presence of the low-affinity PBP2A. The observations suggest that
      cell-wall synthesis in the presence of beta-lactam antibiotics requires the
      cooperative functioning of the transglycosylase domain of the native
      staphylococcal PBP2 and the transpeptidase domain of the PBP2A, a protein
      imported by S. aureus from an extra species source.

PMID- 11517341
TI  - Global differential gene expression in response to growth temperature alteration
      in group A Streptococcus.
AB  - Pathogens are exposed to different temperatures during an infection cycle and
      must regulate gene expression accordingly. However, the extent to which virulent
      bacteria alter gene expression in response to temperatures encountered in the
      host is unknown. Group A Streptococcus (GAS) is a human-specific pathogen that is
      responsible for illnesses ranging from superficial skin infections and
      pharyngitis to severe invasive infections such as necrotizing fasciitis and
      streptococcal toxic shock syndrome. GAS survives and multiplies at different
      temperatures during human infection. DNA microarray analysis was used to
      investigate the influence of temperature on global gene expression in a serotype
      M1 strain grown to exponential phase at 29 degrees C and 37 degrees C.
      Approximately 9% of genes were differentially expressed by at least 1.5-fold at
      29 degrees C relative to 37 degrees C, including genes encoding transporter
      proteins, proteins involved in iron homeostasis, transcriptional regulators,
      phage-associated proteins, and proteins with no known homologue. Relatively few
      known virulence genes were differentially expressed at this threshold. However,
      transcription of 28 genes encoding proteins with predicted secretion signal
      sequences was altered, indicating that growth temperature substantially
      influences the extracellular proteome. TaqMan real-time reverse transcription-PCR
      assays confirmed the microarray data. We also discovered that transcription of
      genes encoding hemolysins, and proteins with inferred roles in iron regulation,
      transport, and homeostasis, was influenced by growth at 40 degrees C. Thus, GAS
      profoundly alters gene expression in response to temperature. The data delineate
      the spectrum of temperature-regulated gene expression in an important human
      pathogen and provide many unforeseen lines of pathogenesis investigation.

PMID- 11517342
TI  - Loss of presenilin 1 is associated with enhanced beta-catenin signaling and skin
      tumorigenesis.
AB  - Presenilin 1 (PS1) is required for the proteolytic processing of Notch and the
      beta-amyloid precursor protein (APP), molecules that play pivotal roles in cell
      fate determination during development and Alzheimer's disease pathogenesis,
      respectively. In addition, PS1 interacts with beta-catenin and promotes its
      turnover through independent mechanisms. Consistent with this activity, we report
      here that PS1 is important in controlling epidermal cell proliferation in vivo.
      PS1 knockout mice that are rescued through neuronal expression of human PS1
      transgene develop spontaneous skin cancers. PS1-null keratinocytes exhibit higher
      cytosolic beta-catenin and beta-catenin/lymphoid enhancer factor-1/T cell factor
      (beta-catenin/LEF)-mediated signaling. This effect can be reversed by
      reintroducing wild-type PS1, but not a PS1 mutant active in Notch processing but
      defective in beta-catenin binding. Nuclear beta-catenin protein can be detected
      in tumors. Elevated beta-catenin/LEF signaling is correlated with activation of
      its downstream target cyclin D1 and accelerated entry from G(1) into S phase of
      the cell cycle. This report demonstrates a function of PS1 in adult tissues, and
      our analysis suggests that deregulation of beta-catenin pathway contributes to
      the skin tumor phenotype.

PMID- 11517343
TI  - The tumor spectrum in FHIT-deficient mice.
AB  - Mice carrying one inactivated Fhit allele (Fhit +/- mice) are highly susceptible
      to tumor induction by N-nitrosomethylbenzylamine, with 100% of Fhit +/- mice
      exhibiting tumors of the forestomach/squamocolumnar junction vs. 25% of Fhit +/+
      controls. In the current study a single N-nitrosomethylbenzylamine dose was
      administered to Fhit +/+, +/-, and -/- mice to compare carcinogen susceptibility
      in +/- and -/- Fhit-deficient mice. At 29 weeks after treatment, 7.7% of wild
      type mice had tumors. Of the Fhit -/- mice 89.5% exhibited tumors (average 3.3
      tumors/mouse) of the forestomach and squamocolumnar junction; half of the -/-
      mice had medium (2 mm diameter) to large (>2 mm) tumors. Of the Fhit +/- mice 78%
      exhibited tumors (average 2.4 tumors/mouse) and 22% showed medium to large
      tumors. Untreated Fhit-deficient mice have been observed for up to 2 years for
      spontaneous tumors. Fhit +/- mice (average age 21 mo) exhibit an average of 0.94
      tumors of different types; Fhit -/- mice (average age 16 mo) also showed an array
      of tumors (average 0.76 tumor/mouse). The similar spontaneous and induced tumor
      spectra observed in mice with one or both Fhit alleles inactivated suggests that
      Fhit may be a one-hit tumor suppressor gene in some tissues.

PMID- 11517344
TI  - Modifications of cellulose synthase confer resistance to isoxaben and
      thiazolidinone herbicides in Arabidopsis Ixr1 mutants.
AB  - In many higher plants, cellulose synthesis is inhibited by isoxaben and
      thiazolidinone herbicides such as 5-tert-butyl-carbamoyloxy-3-(3-trifluromethyl)
      phenyl-4-thiazolidinone. Semidominant mutations at the IXR1 and IXR2 loci of
      Arabidopsis confer isoxaben and thiazolidinone resistance. Isolation of the IXR1
      gene by map-based cloning revealed that it encodes the AtCESA3 isoform of
      cellulose synthase. The two known mutant alleles contain point mutations that
      replace glycine 998 with aspartic acid, and threonine 942 with isoleucine,
      respectively. The mutations occur in a highly conserved region of the enzyme near
      the carboxyl terminus that is well separated from the proposed active site.
      Although the IXR1 gene is expressed in the same cells as the structurally related
      RSW1 (AtCESA1) cellulose synthase gene, these two CESA genes are not functionally
      redundant.

PMID- 11517345
TI  - Diverse developmental programs of Xenopus laevis metamorphosis are inhibited by a
      dominant negative thyroid hormone receptor.
AB  - Metamorphosis of anuran tadpoles is controlled by thyroid hormone (TH). Here we
      demonstrate that transgenic Xenopus laevis tadpoles expressing a dominant
      negative form of TH receptor-alpha are resistant to a wide variety of the
      metamorphic changes induced by TH. This result confirms that TH receptors mediate
      both early and late developmental programs of metamorphosis as diverse as growth
      in the brain, limb buds, nose and Meckel's cartilage, remodeling of the
      intestine, and death and resorption of the gills and tail.

PMID- 11517346
TI  - The interplay of biology and technology.
AB  - Technologies for biological research arise in multiple ways-through serendipity,
      through inspired insights, and through incremental advances-and they are tightly
      coupled to progress in engineering. Underlying the complex dynamics of technology
      and biology are the different motivations of those who work in the two realms.
      Consideration of how methodologies emerge has implications for the planning of
      interdisciplinary centers and the training of the next generation of scientists.

PMID- 11517348
TI  - A deadly combination of anorexia and hypermetabolism.

PMID- 11517349
TI  - An update: cancer-associated anorexia as a treatment target.
AB  - Loss of appetite is pervasive among patients with advanced cancer. Cancer
      patients cite it as one of their most troubling symptoms. To date, however,
      palliative options remain limited. Megestrol acetate and dexamethasone provide
      only modest relief. Novel agents such as thalidomide, adenosine triphosphate, and
      other cytokine inhibitors merit further investigation.

PMID- 11517350
TI  - What do we really know about the ubiquitin-proteasome pathway in muscle atrophy?
AB  - Studies of many different rodent models of muscle wasting have indicated that
      accelerated proteolysis via the ubiquitin-proteasome pathway is the principal
      cause of muscle atrophy induced by fasting, cancer cachexia, metabolic acidosis,
      denervation, disuse, diabetes, sepsis, burns, hyperthyroidism and excess
      glucocorticoids. However, our understanding about how muscle proteins are
      degraded, and how the ubiquitin-proteasome pathway is activated in muscle under
      these conditions, is still very limited. The identities of the important
      ubiquitin-protein ligases in skeletal muscle, and the ways in which they
      recognize substrates are still largely unknown. Recent in-vitro studies have
      suggested that one set of ubquitination enzymes, E2(14K) and E3(alpha), which are
      responsible for the 'N-end rule' system of ubiquitination, plays an important
      role in muscle, especially in catabolic states. However, their functional
      significance in degrading different muscle proteins is still unclear. This review
      focuses on the many gaps in our understanding of the functioning of the ubiquitin
      proteasome pathway in muscle atrophy, and highlights the strengths and
      limitations of the different experimental approaches used in such studies.

PMID- 11517351
TI  - Catabolic and anabolic signals in bone: therapeutic implications.
AB  - Bone remodelling accounts for the continuous renewal of the adult skeleton, and
      its disturbances constitute the pathophysiological basis of most skeletal
      disorders. Recently identified bone signalling pathways explain the action of
      known therapeutic agents and provide targets for new developments in the
      management of bone diseases.

PMID- 11517352
TI  - Clinical and pharmaceutical management of deficiencies, excesses and infection
      with nutrition support.

PMID- 11517353
TI  - Surgical treatment of morbid obesity.
AB  - The prevalence of obesity is increasing rapidly, and it is a major health
      problem, especially in Western countries. Bariatric surgery causes significant
      and permanent weight loss and improves the quality of life. It ameliorates or
      eliminates most of the obesity-related comorbidities. Isolated gastric
      restriction procedures are technically easy to perform, the morbidity and
      mortality are low, but the weight loss is unsatisfactory in patients who ingest
      high-energy food. Combined gastric restriction with gastric bypass or intestinal
      malabsorption procedures cause greater weight loss, but more nutritional
      complications.

PMID- 11517354
TI  - Complications of central venous catheters.
AB  - Central vein catheterization is frequently employed for monitoring,
      administration of drugs and parenteral nutrition in a variety of medical and
      surgical illnesses. Despite the widespread use of central vein access, both
      catheter-related infections and mechanical complications remain unacceptably
      common. In the last few years, data have become available to show that technical
      innovations and catheter maintenance protocols can reduce both catheter related
      bloodstream infections as well as mechanical complications. Future developments
      should be aimed at both educational intervention and biomaterials research. The
      former incorporates case-based instruction, problem-solving examination, and
      database analysis; while the latter will probably lead to a new set of catheters
      that are more resistant to infection and thrombosis.

PMID- 11517355
TI  - Evidence-based prevention of catheter infection during parenteral nutrition.
AB  - Parenteral nutrition is a risk factor for catheter-related bloodstream infection.
      Here we reviewed strategies for the prevention of catheter-related infections,
      which always must begin with the cornerstone of prevention: the strict adherence
      to aseptic techniques. Most research has been interested in coated catheters.
      From these results, it may be concluded that antibiotics or antiseptic
      impregnated catheters, like those with minocycline-rifampicin or
      chlorhexidine/silver sulfadiazine, significantly reduce catheter-related blood
      stream infections. Antibiotics or antiseptic-impregnated central venous catheters
      may even result in cost saving in intensive care units. Antiseptic or antibiotic
      lock techniques would also be of interest to prevent catheter-related sepsis in
      high-risk patients who are receiving parenteral nutrition.

PMID- 11517356
TI  - Practical implications of nutritional support during continuous renal replacement
      therapy.
AB  - Continuous blood membrane interactions during continuous renal replacement
      therapy cause bioincompatibility and low grade inflammatory reactions with
      potentially adverse consequences on protein metabolism and immunocompetence. In
      designing a nutritional program for patients receiving this treatment, these
      adverse metabolic effects, especially the loss of nutritional substrates, must be
      considered. This review provides a practical overview of nutritional support in
      acute renal failure, including assessment techniques, determination of nutrient
      needs, and appropriate intervention for patient support.

PMID- 11517357
TI  - Phosphate supplementation for hypophosphataemia and parenteral nutrition.
AB  - Routine detection and treatment of acute hypophosphataemia is important in
      intensive care unit and many other hospitalized patients, but metabolic bone
      disease and hypophosphataemia are still experienced as a result of parenteral
      nutrition. A significantly common problem that faces the compounding pharmacist
      when formulating parenteral nutrition regimens is the difficulty associated with
      the successful avoidance of calcium phosphate precipitation. Although
      incorporation of the normal calcium and phosphate requirements into regimens for
      metabolically stable adults is usually achievable, it can prove impossible in
      paediatric and neonatal mixtures when using the standard inorganic sources that
      are currently licensed for use in the UK and USA. In other countries, where
      organic compounds are routinely available, this problem does not exist.

PMID- 11517358
TI  - Shoulder arthroplasty for the treatment of the sequelae of fractures of the
      proximal humerus.
AB  - The purpose of this multicenter study was to analyze the results of shoulder
      arthroplasty for the treatment of the sequelae of proximal humerus fractures and
      establish an updated classification system and treatment guidelines for these
      complex situations. Seventy-one sequelae of proximal humerus fractures were
      treated with shoulder replacement with the use of the same nonconstrained,
      modular, and adaptable prosthesis: the Aequalis prosthesis (Tornier Inc, St
      Ismier, France). The average time between initial fracture and shoulder
      arthroplasty was 5 years and 5 months. On the basis of anatomic classification
      schemes, sequelae were divided into 4 types: type 1, humeral head collapse or
      necrosis with minimal tuberosity malunion (40 cases); type 2, locked dislocations
      or fracture-dislocations (9 cases); type 3, nonunions of the surgical neck (6
      cases); and type 4, severe malunions of the tuberosities (16 cases). The mean
      postoperative follow-up was 19 months (range, 12 to 48 months). Overall, the
      postoperative Constant score was excellent in 11 cases (16%), good in 19 cases
      (26%), fair in 18 cases (25%), and poor in 23 cases (33%). There were 18
      complications (27%). Fifty-nine of 70 patients (81%) stated that they were
      satisfied with the result. The most significant factor affecting functional
      outcome was greater tuberosity osteotomy (P <.005). Regarding both surgical
      treatment and postoperative prognosis, we identify 2 categories of proximal
      humerus fracture sequelae: category 1, intracapsular/impacted fractures sequelae
      (associated with both cephalic collapse or necrosis [type 1] and chronic
      dislocation or fracture-dislocation [type 2]), in which an articulating joint can
      be reconstructed without a greater tuberosity osteotomy; and category 2,
      extracapsular/disimpacted fractures sequelae (associated with both surgical neck
      nonunions [type 3] and severe tuberosity malunions [type 4]) where the proximal
      humerus cannot be reconstructed without a greater tuberosity osteotomy. All of
      the excellent and good postoperative Constant scores were obtained in type 1 and
      2, in which osteotomy of the greater tuberosity was not required. All patients in
      type 3 and 4, who underwent a greater tuberosity osteotomy, had either fair or
      poor results and did not regain active elevation above 90 degrees. We conclude
      that a greater tuberosity osteotomy is the most likely reason for poor and
      unpredictable results after shoulder replacement arthroplasty for the treatment
      of the complex sequelae of proximal humerus fractures. Shoulder arthroplasty for
      the treatment of the sequelae of fractures of the proximal humerus should be
      performed without an osteotomy of the greater tuberosity when possible. If
      prosthetic replacement is possible without an osteotomy, surgeons should accept
      the distorted anatomy of the proximal humerus and adapt the prosthesis and their
      technique to the modified anatomy. A modular and adaptable prosthesis with both
      adjustable offsets and inclination may allow surgeons to adapt to a large number
      of malunions and may help to avoid the troublesome greater tuberosity osteotomy
      in a higher proportion of cases.

PMID- 11517359
TI  - Shape of the acromion: congenital or acquired--a macroscopic, radiographic, and
      microscopic study of acromion.
AB  - Debate continues as to whether the differing shapes of the acromion are
      congenital or acquired. This has been investigated by neonatal cadaver study,
      adult cadaver study, radiographic study, magnetic resonance imaging study, or
      various other means. No one, to our knowledge, has investigated this by
      histologic study. A macroscopic and histologic study of 22 cadaveric shoulder
      joints was carried out to establish what, if any, developmental changes occur in
      the differing patterns of acromion. The cadaveric shoulders were dissected and
      examined macroscopically. All of the acromion processes were transected and
      photographed, and the histology of the anterior and inferior surfaces was
      studied. In all of the curved and hooked types of acromion, a common pattern of
      degeneration of collagen, fibrocartilage, and bone was observed, consistent with
      a traction phenomenon. None of the flat acromions exhibited these changes.
      Extensive histologic changes were noted on the anterior surface of acromion as
      compared to the inferior surface in curved or hooked acromion. We conclude that
      the different shapes of acromion are, therefore, acquired as a response to
      traction forces applied via the coracoacromial ligament and are not congenital in
      origin.

PMID- 11517360
TI  - Regeneration of the coracoacromial ligament after acromioplasty and arthroscopic
      subacromial decompression.
AB  - The clinical observation of apparent and complete regeneration of the
      coracoacromial ligament after known partial excision of the ligament and
      acromioplasty has been investigated. Ten patients who had open revision surgery
      following failure of symptomatic relief after arthroscopic subacromial
      decompression were studied. All of them had acromioplasty with documented partial
      resection of the coracoacromial ligament at the first operation. There were 5 men
      and 5 women with an average age of 54.5 years (range, 44-65 years). In all
      patients surgery revealed a ligamentous structure resembling the coracoacromial
      ligament that was attached to the anterior acromion. Histology in all patients
      revealed appearances indistinguishable from normal ligament, which was in
      continuity with the reformed periosteum of the acromion.

PMID- 11517361
TI  - Biomechanical effects of malposition of tuberosity fragments on the humeral
      prosthetic reconstruction for four-part proximal humerus fractures.
AB  - Variable outcomes in the prosthetic reconstruction of 4-part humerus fractures
      often can be attributed to inconsistent and nonanatomic tuberosity placement. To
      compare the effects of anatomic (anterior fin) versus nonanatomic (lateral fin)
      tuberosity placement, we developed a dynamic cadaver model for shoulder motion.
      With the use of a robotically driven, computer-controlled articulator, we tested
      external rotation torque in 5 fresh human shoulders. After evaluation of the
      intact shoulders, we experimentally induced 4-part humerus fractures in the
      specimens. These were then repaired by hemiarthroplasty, with the use of standard
      techniques to secure the greater and lesser tuberosities in either anatomic or
      nonanatomic positions; order was randomized. Nonanatomic tuberosity
      reconstruction led to significant impairment in external rotation kinematics and
      an 8-fold increase in torque requirements (P =.001). In contrast, anatomic
      reconstruction produced results indistinguishable from normal shoulder controls.
      This study underscores the importance of rotational alignment of tuberosities
      during reconstruction. Failure to properly position tuberosity fragments in the
      horizontal plane may result in insurmountable postoperative motion restriction.

PMID- 11517362
TI  - Glenoid size, inclination, and version: an anatomic study.
AB  - Three hundred forty-four human scapular bones (172 matched pairs) were measured
      for their glenoid height, width, inclination, and version. The sample consisted
      of 50 black men, 50 white men, 50 black women, and 22 white women, all of whom
      were aged 20 to 30 years at the time of death. The mean age of the study group
      was 25.6 years. No difference in glenoid size was noted between black and white
      patients. The overall glenoid version for the entire study group was 1.23 degrees
      of retroversion. The difference in glenoid version between black and white
      patients was statistically significant. The average glenoid version for black and
      white patients measured 0.20 degrees and 2.65 degrees of retroversion,
      respectively (P =.000014). Specifically, the glenoid version for black and white
      men measured 0.11 degrees and 2.87 degrees of retroversion, respectively (P
      =.00034). The glenoid version for black and white women measured 0.30 degrees and
      2.16 degrees of retroversion, respectively (P =.034). No statistical difference
      in glenoid version was found between men and women of the same race. No
      difference was found between measuring the glenoid version based on the
      transverse axis of the scapula and measuring the glenoid version perpendicular to
      the glenohumeral joint. No statistical difference was found in the glenoid
      inclination based on race or sex. The relationships between glenoid size,
      inclination, and version are important to understand when a surgeon prepares to
      resurface the glenoid during total shoulder arthroplasty. The knowledge of these
      values, their variation, and racial differences should help reproduce a more
      anatomical result.

PMID- 11517363
TI  - Shrinkage in the inferior pouch of the scapulohumeral joint is related to
      postoperative pain after rotator cuff repair: radiographic and arthrographic
      comparison between patients with postoperative pain and those without it.
AB  - Fluoroscopic and arthrographic studies were performed in 50 patients to determine
      whether pain in the shoulder after rotator cuff repair was related to the
      restricted movement of the glenohumeral joint. The 50 patients were divided into
      2 groups: group A consisted of 22 patients with mild shoulder pain for more than
      1 year postoperatively, and group B consisted of the remaining 28 patients
      without pain after surgery. The motion in the scapulothoracic articulation and
      that in the glenohumeral joint were analyzed separately by measurement of the
      scapular motion on radiographs taken under fluoroscopic control. The glenohumeral
      joint capacity was measured by arthrography. Changes in the glenoid tilting angle
      with shoulder elevation were significantly greater in group A than those in group
      B. Patients in group A demonstrated a significantly smaller inferior pouch on
      arthrograms than those in group B. The patients with shoulder pain after rotator
      cuff repair thus had reduced capacity and motion of the glenohumeral joint.

PMID- 11517364
TI  - Anterior-inferior capsular shift of the shoulder: a biomechanical comparison of
      glenoid-based versus humeral-based shift strategies.
AB  - This study compared the biomechanical effects of an anterior-inferior capsular
      shift based at the humeral side with one on the glenoid side of the joint on
      resultant multidirectional glenohumeral translation and rotation. Nine matched
      pairs of fresh cadaveric shoulders were placed in a testing apparatus that
      constrained 3 rotations but allowed simultaneous free translation of the humeral
      head with respect to the glenoid. The right and left shoulders of each of the
      matched pairs were randomized to undergo either a glenoid-based or humeral-based
      anterior capsular shift. The shoulders were tested vented and following the
      capsular shift procedure. Translational testing was performed at 0 degrees, 45
      degrees, and 90 degrees of glenohumeral elevation with the humerus in neutral
      rotation, 30 degrees internal rotation, and 30 degrees external rotation.
      Sequential loads of 30 N in anterior, posterior, and inferior directions were
      applied while maintaining a 22-N joint compressive load. The maximum arc of
      internal and external rotation after application of a 1-newton-meter moment was
      determined for the vented specimens and then after the capsular shift procedure.
      Both shift strategies resulted in significant limitation of anterior, posterior,
      and inferior translation in all of the tested positions. No significant
      differences were noted between the 2 shift strategies with respect to restriction
      of translation in the anterior or inferior directions. The glenoid-based shift
      caused a significantly greater decrease in posterior translation at 45 degrees
      and 90 degrees of abduction. With respect to rotation, the glenoid-based shift
      exerted significantly greater restriction on external rotation than the humeral
      based shift. This study supports the use of either a humeral-based or glenoid
      based shift to control multidirectional glenohumeral instability. Greater
      reduction in external rotation was demonstrated after the glenoid-based shift.
      Specific differences demonstrated in translation control for humeral-based versus
      glenoid-based capsular shift procedures may be useful in tailoring a procedure
      for specific instability patterns.

PMID- 11517365
TI  - Open surgical release for frozen shoulder: surgical findings and results of the
      release.
AB  - Over a 5-year period, 75 shoulders that met Codman's criteria for primary frozen
      shoulder were treated. Nine patients improved with nonoperative treatment, and
      the remaining 66 patients underwent manipulation under anesthesia. The shoulders
      in 41 patients successfully released with manipulation. Those in 25 failed to
      release with manipulation, and therefore, these patients underwent open surgical
      release of the contracted shoulder. We reviewed the cases of all of the
      surgically treated patients at 19.52 months' average follow-up, using the history
      and clinical examination technique recommended by the American Shoulder and Elbow
      Surgeons. The surgical findings in this group of 25 patients showed a consistent
      alteration in the rotator interval and coracohumeral ligament. The rotator
      interval was obliterated, and the coracohumeral ligament was transformed into a
      tough contracted band. The histology of this contracture was examined in 12
      patients and consisted of a dense matrix of type III collagen populated with
      fibroblasts and myofibroblasts. The contracted coracohumeral ligament was excised
      with immediate release of the external rotation deficit. Pain scores on visual
      analogue scale improved from 8.28 to 2.0. The average score for function, with a
      maximum score of 30, improved from 6.08 to 18.9. Twenty patients had excellent or
      good results, and 3 had fair results. The shoulders of 2 patients failed to
      improve: 1 was an insulin-dependent patient with diabetes, and 1 had severe
      bilateral Dupuytren's contractures. The results in the patients without diabetes
      were very satisfactory, with visual analogue scale scores of pain decreasing from
      8.4 to 1.1, function increasing from 6.4 to 20.1, flexion increasing from an
      average of 96 degrees to an average of 131 degrees, and external rotation
      increasing from an average of 10.0 degrees to an average of 46.7 degrees.
      Surgical release of frozen shoulder is a useful option in those few patients with
      severe disease whose shoulders fail to release with manipulation under
      anesthesia. Caution should be used in insulin-dependent patients with diabetes.

PMID- 11517366
TI  - Intraoperative measurement of shoulder translation.
AB  - Assessing laxity of the shoulder joint in patients who are under anesthesia is a
      standard procedure before arthroscopy. The aim of this study was to evaluate a
      novel instrument for quick and reliable intraoperative measurement of
      glenohumeral translation. Previous testing of various designs has resulted in a
      device secured by 1 pin in the acromion and 1 pin in the proximal humerus. These
      pins are interconnected by a sliding ruler that gives translation values in
      millimeter increments as the laxity tests are performed. Comparison between
      manual arbitrary approximation of laxity and instrumented translation
      measurements showed that manual testing is reasonably good for assessment of
      anterior and posterior translation, without, however, providing values of
      translation in millimeter increments. The low correlation between manual
      assessment and instrumented inferior translation measurements indicates that
      inferior translation is more difficult to approximate manually. The shoulder
      translation tester was used in 102 patients. The mean values for clinically
      stable shoulders (n = 58) were 5 mm for anterior translation, 5 mm for posterior
      translation, and 4 mm for inferior translation. The corresponding values in
      unstable shoulders were significantly higher than in the stable shoulders,
      especially in patients with multidirectional instability. We conclude that the
      shoulder translation tester is easy and quick to use. It provides quantitative
      values of translation and will thus contribute information for correct diagnosis,
      therapy, and documentation.

PMID- 11517367
TI  - Resection interposition arthroplasty of the shoulder affected by inflammatory
      arthritis.
AB  - To determine the therapeutic value of resection-interposition arthroplasty (RIAP)
      of shoulders in rheumatoid or other inflammatory arthritis, 53 patients were
      reviewed clinically and radiographically after a mean follow-up period of 8.2 +/-
      4.3 years (3.5 to 17.5 years). The Constant Score averaged 42.33 +/- 16.2 (12 to
      76). Patients with a follow-up period of more than 10 years performed
      significantly worse than those with shorter follow-up periods. In most cases,
      radiographs showed a progressive medial displacement and loss of size of the
      humeral head as well as a decrease of the joint space with time. Abduction proved
      to be highly dependent on the degree of medial displacement of the humeral head,
      whereas the Constant Scores correlated with the width of the joint space. Despite
      initially acceptable postoperative results, outcome at longer follow-up periods
      worsened as the result of wear of the glenoidal cartilage and osseous resorption
      of the humeral head, resulting in a progressive medialization of the center of
      rotation.

PMID- 11517368
TI  - Injury of the suprascapular nerve in shoulder surgery: an anatomic study.
AB  - Fifty-two shoulders in 26 cadavers were dissected to evaluate the safe zone for
      avoiding injury of the suprascapular nerve during open surgical procedures and
      arthroscopic Bankart repairs requiring blind drilling. The course of the
      suprascapular nerve was given as the shortest distance between the suprascapular
      nerve and the glenoid rim. A Kirschner wire was inserted from the anterior
      glenoid rim toward the suprascapular nerve. The insertion angle toward the
      suprascapular nerve at the base of the scapular spine in the transverse plane
      averaged 37.0 degrees and in the sagittal plane averaged 17.5 degrees. The
      insertion angle toward the bifurcation of the infraspinatus motor branch in the
      transverse plane averaged 44.3 degrees and in the sagittal plane averaged 27.7
      degrees. On the basis of the results of the anatomic evaluation, the safe zone
      was described. An appreciation of this safe zone may help shoulder surgeons avoid
      iatrogenic injury to the suprascapular nerve.

PMID- 11517369
TI  - Partial rupture of the distal biceps tendon.
AB  - We report on 7 cases of partial rupture of the distal biceps tendon. The mean
      patient age was 52 years (range, 38-58 years). There were 5 men and 2 women. The
      dominant arm was affected in all 7 patients. Pain was the chief complaint in all
      patients. Immobilization and physiotherapy were attempted in all patients, and 4
      had at least 1 local steroid injection. No patient improved from the conservative
      treatment. All patients eventually underwent surgical debridement and
      reattachment of the biceps tendon with use of a 1-incision technique with suture
      anchors. After a mean follow-up of 31 months (range, 25-44 months), all patients
      reported a significant decrease in their pain. No complications were noted.

PMID- 11517370
TI  - Posterior surgical approaches to the elbow: a comparative anatomic study.
AB  - Triceps splitting, triceps reflecting, and olecranon osteotomy are the most
      common posterior surgical approaches to the adult elbow, but no comparative data
      exist as to the exposure provided by each approach. The aim of this study was to
      determine which of these approaches provides the greatest exposure of the distal
      humeral articular surface. Each approach was performed on 4 adult cadaveric
      elbows. After the completion of each approach, the visible articular surface was
      painted with methylene blue. The elbow was then disarticulated, and the
      percentage of articular surface visible was measured. The median exposed
      articular surface for the triceps splitting, triceps reflecting, and olecranon
      osteotomy approaches was 35%, 46%, and 57%, respectively. Olecranon osteotomy
      exposed more articular surface than the triceps splitting approach (Mann-Whitney
      test, P =.03) but was not significantly greater than the triceps reflecting
      approach. However, even the olecranon osteotomy approach failed to provide
      visualization of more than 40% of the distal humeral articular surface.

PMID- 11517371
TI  - Recurrent shoulder dislocation secondary to chronic synovitis in sickle cell
      disease: a case report.

PMID- 11517372
TI  - Nonunion of a fracture of the body of the scapula: case report and literature
      review.

PMID- 11517373
TI  - Recurrent inferior dislocation of the acromioclavicular joint: a report of two
      cases.

PMID- 11517382
TI  - Peripheral nerve protein, P0, as a potential receptor for Theiler's murine
      encephalomyelitis virus.
AB  - Theiler's murine encephalomyelitis virus (TMEV) belongs the family
      Picornaviridae. TMEV not only replicates in the gastrointestinal tract but also
      spreads to the central nervous system (CNS) either by a hematogenous or a neural
      pathway during natural infection. The DA strain of TMEV infects neurons during
      the acute phase, and glial cells and macrophages during the chronic phase,
      leading to a demyelinating disease similar to multiple sclerosis. Different virus
      host receptor interactions in the peripheral and the neuronal cells could explain
      the pathways of viral spread from the peripheral to the CNS and neurons to glial
      cells. However, the receptor for TMEV remains unknown. P0 protein, a 28-31 kD
      glycoprotein, belongs to the immunoglobulin superfamily and constitutes 50% of
      the total myelin protein in the peripheral nerve. Other picornaviruses use
      members of the immunoglobulin superfamily as receptors. Thus we hypothesized P0
      protein could act as a receptor for TMEV. In a virus overlay assay, radiolabeled
      TMEV bound to a 28-30 kD protein from the peripheral nerve of wild-type C57BL/6,
      but no binding was found in the peripheral nerve from P0-knockout mice. TMEV
      replicated fourfold higher in P0-transfected BW5147.G.1.4 cells than in mock
      transfected cells. The increase in virus replication in the P0-transfected cell
      line was blocked by preincubation of the cells with anti-P0 antibody. A virus
      binding study showed that TMEV bound to P0-transfected cells but not to mock
      transfected cells. The use of the P0 protein in Schwann cells as a receptor may
      be one mechanism by which TMEV spreads from the gastrointestinal tract to the
      CNS.

PMID- 11517383
TI  - Differences in pathogenicity of herpes simplex virus serotypes 1 and 2 may be
      observed by histopathology and high-resolution magnetic resonance imaging in a
      murine encephalitis model.
AB  - The mouse model for herpes simplex-induced encephalitis (HSE) is an established
      preclinical tool for evaluating the efficacy of new therapeutic interventions. We
      evaluated the utility of high-resolution in vivo MRI in observing the progression
      of experimental HSE during the first week postinfection. Female BALB/c mice were
      inoculated intracerebrally with HSV-1 or HSV-2 by microinjection. Each animal was
      evaluated daily by high-resolution (4.7 Tesla) T(2) weighted MRI and clinical
      disease scoring (neurological and behavioral). Lesions induced by a high dose of
      HSV-1 (1000 PFU) were detectable by MRI without administration of contrast agent
      whereas for low dose HSV-1 (100 PFU), administration of contrast agent was
      necessary to visualize the lesions in the brain. The correlation between the MRI
      and histologic results was excellent. No HSV-2 induced lesions were observed by
      MRI. Although both HSV serotypes caused similar clinical disease, significant
      type differences were found by histologic and MRI examinations. HSV-1 caused
      necrotizing meningoencephalitis, whereas HSV-2 induced mostly meningitis. The
      data indicate that in vivo high-resolution MRI may be useful to longitudinally
      evaluate HSV-1-related pathology in a mouse model of HSE and potentially could be
      used for monitoring the efficacy of anti-infective therapeutic approaches.

PMID- 11517381
TI  - HIV in the CNS: pathogenic relationships to systemic HIV disease and other CNS
      diseases.
AB  - Research on the pathogenesis of the human immunodeficiency virus (HIV) infection
      of the central nervous system (CNS) has reached a pivotal stage. While the
      incidence of HIV dementia appears to be declining, the prevalence of milder, yet
      debilitating, neuropsychological impairments may rise as individuals infected
      with HIV live longer. There are also concerns about CNS reservoirs of latently
      infected cells. Building upon progress in understanding HIV neuropathogenesis,
      the time is ideal to expand research on the interrelationships between the CNS
      and systemic HIV disease, and extend the boundaries of this research to the
      neuropathogenic similarities between HIV and other CNS inflammatory diseases.
      Neuropathogenic insights gained from these pursuits can spawn new treatment
      strategies for HIV/CNS disease as well as potentially other diseases of the
      nervous system.

PMID- 11517384
TI  - Persistence of the influenza A/WSN/33 virus RNA at midbrain levels of
      immunodefective mice.
AB  - Strains of influenza A virus are known to infect specific subpopulations of
      neurons in the mouse brain. Here we report that all segments of the genome of the
      neurotropic influenza A virus, strain WSN/33, can persist in the brains of
      immunodefective transporter associated with Antigen Processing 1 (TAP1) mutant
      mice. Ten to 17 months after injection of virus into the olfactory bulbs, viral
      RNA encoding the nonstructural NS1 protein was detected in sections from the
      brain at midbrain levels by RT-PCR in almost all animals. Both negative-strand
      genomic RNA (vRNA) and positive-strand RNA, including mRNA, were found. RNA
      encoding nucleoprotein and polymerases, which form the replicative complex of the
      virus, were detected in fewer brains. RNA encoding envelope proteins were found
      only in occasional brains. No viral cDNA could be identified. This observation
      shows that certain regions of the brain in immunodefective mice may harbor the
      genome of influenza A virus including the NS1 gene, the products of which may
      play a regulatory role in host-cell metabolism.

PMID- 11517386
TI  - Cytomegalovirus induces cytokine and chemokine production differentially in
      microglia and astrocytes: antiviral implications.
AB  - Glial cells function as sensors for infection within the brain and produce
      cytokines to limit viral replication and spread. We examined both cytokine (TNF
      alpha, IL-1beta, and IL-6) and chemokine (MCP-1, MIP-1alpha, RANTES, and IL-8)
      production by primary human glial cells in response to cytomegalovirus (CMV).
      Although CMV-infected astrocytes did not produce antiviral cytokines, they
      generated significant quantities of the chemokines MCP-1 and IL-8 in response to
      viral infection. On the other hand, supernatants from CMV-stimulated purified
      microglial cell cultures showed a marked increase in the production of TNF-alpha
      and IL-6, as well as chemokines. Supernatants from CMV-infected astrocyte
      cultures induced the migration of microglia towards chemotactic signals generated
      from infected astrocytes. Antibodies to MCP-1, but not to MIP-1alpha, RANTES, or
      IL-8, inhibited this migratory activity. These findings suggest that infected
      astrocytes may use MCP-1 to recruit antiviral cytokine-producing microglial cells
      to foci of infection. To test this hypothesis, cocultures of astrocytes and
      microglial cells were infected with CMV. Viral gene expression in these
      cocultures was 60% lower than in CMV infected purified astrocyte cultures lacking
      microglia. These results support the hypothesis that microglia play an important
      antiviral role in defense of the brain against CMV. The host defense function of
      microglial cells may be directed in part by chemokines, such as MCP-1, produced
      by infected astrocytes.

PMID- 11517385
TI  - Gp120 activates children's brain endothelial cells via CD4.
AB  - Encephalopathy represents a common and serious manifestation of HIV-1 infection
      in children, but its pathogenesis is unclear. We demonstrated that gp120
      activated human brain microvascular endothelial cells (HBMEC) derived from
      children in up-regulating ICAM-1 and VCAM-1 expression, IL-6 secretion and
      increased monocyte transmigration across monolayers. Another novel observation
      was our demonstration of CD4 in isolated HBMEC and on microvessels of children's
      brain cryosections. Gp120-induced monocyte migration was inhibited by anti-gp120
      and anti-CD4 antibodies. This is the first demonstration that gp120 activates
      HBMEC via CD4, which may contribute to the development of HIV-1 encephalopathy in
      children.

PMID- 11517387
TI  - Infection and establishment of latency in the dog brain after direct inoculation
      of a nonpathogenic strain of herpes simplex virus-1.
AB  - A number of diseases affecting the CNS occur in the dog and can be used as models
      for gene therapy in a large brain. HSV-1 has several potential advantages as a
      vector to transfer genes into the CNS. However, the ability of HSV-1 to infect
      CNS cells varies among species and no information was available for the dog. When
      the nonpathogenic 1716 strain of HSV-1 was injected into the brains of normal
      dogs it established a latent infection without signs of pathology. Thus, it
      appears to be suitable as a vector for therapeutic, or marker genes, in this
      species.

PMID- 11517388
TI  - CD4/CXCR4-independent infection of human astrocytes by a T-tropic strain of HIV
      1.
AB  - HIV-1 establishes a low-level persistent infection in astrocytes. In this study,
      we studied the susceptibility of a human astrocyte cell line (SVG-A) to infection
      with luciferase expressing reporter viruses pseudotyped with envelopes derived
      from five isolates of HIV-1. SVG-A cells were susceptible to infection by a T
      cell tropic isolate and the infection was both CD4 and CXCR4 independent. These
      data confirm the susceptibility of astrocytes to infection with T-tropic strains
      of HIV-1 and suggest a novel mechanism by which T-tropic strains of HIV can
      infect cells.

PMID- 11517389
TI  - Herpesvirus quiescence in neuronal cells IV: virus activation induced by
      pituitary adenylate cyclase-activating polypeptide (PACAP) involves the protein
      kinase A pathway.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) is a naturally
      occurring peptide found in the central nervous system that plays a role in
      somatosensory processing and activation of protein kinase A (PKA) and protein
      kinase C (PKC). Because activation of PKA or PKC results in reactivation of HSV-1
      from latently infected embryonic neuronal cells, PACAP was used to evaluate HSV-1
      activation from quiescently infected (QIF)-PC12 cells. Our studies demonstrate
      that physiologically relevant concentrations of PACAP38 and PACAP27 induce HSV-1
      activation from QIF-PC12 cell cultures in a dose-dependent fashion. PACAP-induced
      activation of virus was significantly impaired by the PKA-inhibitor, H-89 (20
      microM), whereas treatment with the PKC-inhibitor, GF109203X (1 microM), was
      without affect. Additionally, direct activation of PKA with cAMP analogs, 8-(4
      chlorophenylthio)- and dibutyryl-cAMP, only partially mimicked the effect of
      PACAP on virus activation. Taken together, PACAP induced HSV-1 activation from
      QIF-PC12 cells involves the PKA and possibly cAMP-independent pathways. This
      report is the first to demonstrate that PACAP induces HSV-1 activation from a
      quiescent state and that this in vitro cell model is useful for studying early
      inductive events that lead to virus production from quiescence.

PMID- 11517390
TI  - Insertional mutagenesis of preneoplastic astrocytes by Moloney murine leukemia
      virus.
AB  - Retroviral infection can induce transcriptional activation of genes flanking the
      sites of proviral integration in target cells. Because integration is essentially
      random, this phenomenon can be exploited for random mutagenesis of the genome,
      and analysis of integration sites in tumors may identify potential oncogenes.
      Here we have investigated this strategy in the context of astrocytoma
      progression. Neuroectodermal explants from astrocytoma-prone GFAP-v-src
      transgenic mice were infected with the ecotropic Moloney murine leukemia virus
      (Mo-MuLV). In situ hybridization and FACS analysis indicated that astrocytes from
      E12.5-13.5 embryos were highly susceptible to retroviral infection and expressed
      viral RNA and proteins both in vitro and in vivo. In average 80% of
      neuroectodermal cells were infected in vitro with 9-14 proviral integrations per
      cell. Virus mobility assays confirmed that Mo-MuLV remained transcriptionally
      active and replicating in neuroectodermal primary cultures even after 45 days of
      cultivation. Proviral insertion sites were investigated by inverse long-range
      PCR. Analysis of a limited number of provirus flanking sequences in clones
      originated from in vitro infected GFAP-v-src neuroectodermal cells identified
      loci of possible relevance to tumorigenesis. Therefore, the approach described
      here might be suitable for acceleration of tumorigenesis in preneoplastic
      astrocytes. We expect this method to be useful for identifying genes involved in
      astrocytoma development/progression in animal models.

PMID- 11517391
TI  - Effect of extracellular HIV-1 Vpr protein in vitro.

PMID- 11517393
TI  - Virus receptors in the human central nervous system.
AB  - The initial event in the life cycle of a virus is its interaction with receptors
      present on the surface of a cell. Understanding these interactions is important
      to our understanding of viral tropism, spread, and pathogenesis. This is
      particularly true of viruses that target the central nervous system as these
      viruses must maintain a tropism for both the nervous system and for peripheral
      organs that allow for viral replication and spread to new susceptible hosts.
      These viruses therefore interact with a diverse set of cells and tissues,
      interactions that are likely mediated by both common and unique receptors present
      on each target tissue. In addition, physiological changes in the host can lead to
      increased or decreased expression of virus receptors, which influence virus
      trafficking, spread, and tissue specific pathology. This review will focus on the
      relatively few virus receptor systems that have been described in some level of
      detail for viruses that target the human central nervous system.

PMID- 11517394
TI  - Interactions between HIV-1 gp120, chemokines, and cultured adult microglial
      cells.
AB  - HIV dementia (HIVD), a disease that is apparently mediated by neurotoxins and
      viral proteins secreted by HIV infected microglia, is characterized
      neuropathologically by an increased number of activated microglia in the brains
      of affected individuals. Consequently, the rational design of potential
      therapeutic strategies should take into account the mechanisms that lead to
      microglial activation and to their increased prominence in the adult brain. In
      this regard, one leading hypothesis proposes that microglia are recruited to
      specific sites in the central nervous system (CNS) as a result of interactions
      between microglial chemokine receptors and chemokines, or even the viral
      glycoprotein gp120, which binds chemokine receptors in the process of cellular
      entry. Adult microglia express the functional chemokine receptors CCR5 and CXCR4
      molecules that mediate chemotaxis in these and other cell types. We determined
      that purified adult microglial cultures contain a heterogeneous population with
      respect to their ability to respond to the alpha- and beta-chemokines, SDF1alpha,
      and MIP-1beta. A mean of 14.6% of the microglia assayed responded to both alpha-
      and beta-chemokines (CCR5(+)CXCR4(+) phenotype); 45.4% of microglia were
      phenotyped as CCR5(+)CXCR4(-); 12.9% of the microglia were CXCR4(+)CCR5(-); and
      27.0% of microglia did not respond to either chemokine. No increase in
      intracellular calcium levels was seen in the vast majority of microglia exposed
      to the soluble HIV envelope protein, gp120, or to HIV envelope (gp120/gp41)
      expressed on MLV virus pseudotypes. However, exposure of microglia to soluble
      fractalkine or to other chemokines resulted in an intracellular calcium flux. Our
      results raise the possibility of microglial heterogeneity with respect to their
      response to chemokines, and indicate that any effects due to gp120 are likely to
      be considerably less robust than the response of microglia to the natural ligands
      of their chemokine receptors, for example SDF1alpha and MIP-1beta.

PMID- 11517395
TI  - Robust expression of TNF-alpha, IL-1beta, RANTES, and IP-10 by human microglial
      cells during nonproductive infection with herpes simplex virus.
AB  - Cytokine (TNF-alpha/beta, IL-1beta, IL-6, IL-18, IL-10, and IFN-alpha/beta/gamma)
      and chemokine (IL-8, IP-10, MCP-1, MIP-1alpha/beta, and RANTES) production during
      herpes simplex virus (HSV) 1 infection of human brain cells was examined. Primary
      astrocytes as well as neurons were found to support HSV replication, but neither
      of these fully permissive cell types produced cytokines or chemokines in response
      to HSV. In contrast, microglia did not support extensive viral replication;
      however, ICP4 was detected by immunochemical staining, demonstrating these cells
      were infected. Late viral protein (nucleocapsid antigen) was detected in <10% of
      infected microglial cells. Microglia responded to nonpermissive viral infection
      by producing considerable amounts of TNF-alpha, IL-1beta, IP-10, and RANTES,
      together with smaller amounts of IL-6, IL-8, and MIP-1alpha as detected by RPA
      and ELISA. Surprisingly, no interferons (alpha, beta, or gamma) were detected in
      response to viral infection. Pretreatment of fully permissive astrocytes with TNF
      alpha prior to infection with HSV was found to dramatically inhibit replication,
      resulting in a 14-fold reduction of viral titer. In contrast, pretreatment of
      astrocytes with IL-1beta had little effect on viral replication. When added to
      neuronal cultures, exogenous TNF-alpha or IL-1beta did not suppress subsequent
      HSV replication. Exogenously added IP-10 inhibited HSV replication in neurons
      (with a 32-fold reduction in viral titer), however, similar IP-10 treatment did
      not affect viral replication in astrocytes. These results suggest that IP-10
      possesses direct antiviral activity in neurons and support a role for microglia
      in both antiviral defense of the brain as well as amplification of immune
      responses during neuroinflammation.

PMID- 11517396
TI  - Viruses can silently prime for and trigger central nervous system autoimmune
      disease.
AB  - Although many viruses have been isolated from patients with multiple sclerosis
      (MS), as yet, no one agent has been demonstrated to cause MS. In contrast,
      epidemiological data indicate that viral infections are associated with
      exacerbations of MS. Here, we present data showing that virus infections can
      subclinically prime animals for central nervous system (CNS) autoimmune disease;
      long after the original infection has been eradicated, a nonspecific
      challenge/infection can trigger an exacerbation. The priming infectious agent
      must show molecular mimicry with self-CNS antigens such as glial fibrillary
      acidic protein (GFAP), myelin associated glycoprotein (MAG) or myelin proteolipid
      protein (PLP). The subsequent challenge, however, may be nonspecific; complete
      Freund's adjuvant (CFA), or infection with a recombinant vaccinia virus encoding
      an irrelevant protein, could trigger CNS disease. In the CNS, we could detect a
      mononuclear cell infiltration, but no demyelination was found. However, if the
      pathogenesis of MS is similar to that of this novel animal model for CNS
      autoimmune disease, our findings could help explain why exacerbations of MS are
      often associated with a variety of different viral infections.

PMID- 11517397
TI  - HTLV-I proviral load correlates with progression of motor disability in HAM/TSP:
      analysis of 239 HAM/TSP patients including 64 patients followed up for 10 years.
AB  - To clarify clinical and laboratory findings that may be related to the
      pathomechanism of HTLV-I-associated myelopathy/tropical spastic paraparesis
      (HAM/TSP), we analyzed these findings in 239 patients with HAM/TSP, including 64
      patients followed up for 10 years after their first examinations, with special
      interest in the HTLV-I proviral load in peripheral blood mononuclear cells
      (PBMCs). The proviral load in PBMCs did not differ in terms of modes of HTLV-I
      transmission. However, the proviral load in patients with age of disease onset
      greater than 65 years tended to be higher than those with a younger age of onset.
      In the 64 patients followed up for 10 years, the clinical symptoms deteriorated
      in 36 patients (56%), unchanged in 26 patients (41%), and improved in 2 patients
      (3%). HTLV-I proviral load also appeared to be related to the deterioration of
      motor disability in these patients. To our knowledge, the present study is the
      first longitudinal study concerning the relationship between the clinical course
      of HAM/TSP and HTLV-I proviral load. It is suggested that HTLV-I proviral load is
      related to the progression of motor disability and is an important factor to
      predict prognosis of patients with HAM/TSP.

PMID- 11517399
TI  - JC virus T' proteins encoded by alternatively spliced early mRNAs enhance T
      antigen-mediated viral DNA replication in human cells.
AB  - Alternative splicing of the JC Virus (JCV) precursor early mRNA yields five
      transcripts that encode proteins that regulate the life cycle of this human
      polyomavirus. Large T protein (TAg) mediates viral DNA replication and oncogenic
      activities, and small t protein influences these functions under certain
      conditions. Recently, three new early proteins, T'(135), T'(136), and T'(165),
      were discovered that contain sequences overlapping amino-terminal TAg functional
      domains. Initial studies with the T' proteins suggested they contribute to viral
      DNA replication and transformation. Mutation of a donor splice site utilized by
      all three T' mRNAs creates a mutant that exhibits a 10-fold decrease in viral DNA
      replication compared to wild type JCV. To assess the influence that individual T'
      proteins have on the replication process, a set of T' acceptor site mutants was
      created in which the unique second acceptor splice site of each T' mRNA was
      altered to eliminate production of one, two or all three T' mRNAs. The patterns
      of early mRNA and protein expression in these seven mutants were examined, and it
      was found that mutation of the T'(135) acceptor site resulted in the utilization
      of cryptic splice sites and the generation of new T' species. Additional
      mutations were made to prevent these aberrant splicing reactions prior to
      measuring DNA replication potential of the mutants. DpnI assays revealed that
      each T' protein contributes to TAg-mediated DNA replication activity. The three
      single mutants that express two T' proteins and the double mutant that only
      produces T'(136), exhibited levels of replication equivalent to that of wild type
      virus, whereas the two double mutants that fail to express T'(136) replicated
      about twofold less efficiently than wild-type JCV. Replication activity of the
      triple acceptor site mutant, like that of the T' donor site mutant from an
      earlier study, was impaired significantly.

PMID- 11517398
TI  - HIV-1 LTR C/EBP binding site sequence configurations preferentially encountered
      in brain lead to enhanced C/EBP factor binding and increased LTR-specific
      activity.
AB  - Recent studies have shown that two CAAT/enhancer binding protein (C/EBP) sites
      are critically important for efficient human immunodeficiency virus (HIV) type 1
      (HIV-1) replication within cells of the monocyte/macrophage lineage, a primary
      cell type infected by HIV-1 and a potentially important vehicle for transport of
      virus to the central nervous system (CNS). Given the relevance of HIV-1 LTR
      sequence variation with respect to HIV-1 replication within monocyte populations
      and the important role that monocyte tropism likely plays in HIV-1 infection of
      the brain, C/EBP site sequence variation was examined within peripheral blood-
      and brain-derived LTR populations. Brain-derived LTRs commonly possessed a C/EBP
      site I configuration (6G, comprised of a thymidine to guanosine substitution with
      respect to the clade B consensus sequence at position 6 of C/EBP site I) that
      leads to enhanced binding of C/EBP proteins over that observed with the HIV-1
      clade B consensus sequence at this site. In contrast, the 6GC/EBP site I
      configuration appeared infrequently within sequenced peripheral blood-derived
      LTRs. In addition, C/EBP site II was even more highly conserved in brain-derived
      HIV-1 LTR populations than site I. This was not the case with peripheral blood
      derived LTR C/EBP site II sequences. The high degree of C/EBP site II
      conservation in brain-derived LTRs was likely important in LTR regulation since
      the clade B consensus sequence conserved at C/EBP site II recruited high amounts
      of C/EBP family members. Transient transfection analyses indicated that
      conservation of the strong C/EBP site II in brain-derived LTRs was likely due to
      important interactions with Tat. Overall, brain-derived HIV-1 LTRs preferentially
      contained two highly reactive C/EBP binding sites, which may suggest that these
      sites play important roles in LTR-directed transcription during invasion and
      maintenance of HIV-1 in the central nervous system.

PMID- 11517400
TI  - Age-dependent poliomyelitis in mice is associated with respiratory failure and
      viral replication in the central nervous system and lung.
AB  - Age-dependent poliomyelitis (ADPM) is a virally induced neuroparalytic disease of
      mice and a model for amyotrophic lateral sclerosis (ALS). ADPM is triggered in
      genetically susceptible mice by immunosuppression and infection with lactate
      dehydrogenase-elevating virus (LDV). Both ADPM and ALS are characterized by
      progressive degeneration of anterior horn motor neurons, and death in ALS is
      usually associated with respiratory failure. To assess respiratory function in
      ADPM, we investigated ventilation in conscious control and LDV-infected C58/J
      mice breathing air and then 6.5% CO(2) in O(2). Three days after LDV infection,
      ventilation in response to CO(2) was half of that compared to the uninfected
      state, but become normalized by 10 days. Administration of cyclophosphamide alone
      (200 mg/kg, ip), an immunosuppressant, had no effect on ventilation. Induction of
      ADPM by concomitant administration of LDV to cyclophosphamide-treated mice
      resulted in altered gait, hindlimb paralysis, wasting, decreased metabolism, and
      decreased body temperature by 4 degrees C relative to controls. Compared to
      baseline values, mice with ADPM had decreased tidal volume and ventilation while
      breathing air, and while exposed to the CO(2) challenge they were unable to
      increase tidal volume, frequency of breathing, or ventilation. Using in situ
      hybridization, LDV replication was noted within the spinal cord, brain, and lung,
      but not in the diaphragm. Thus, respiratory failure is a contributory mechanism
      leading to death in ADPM and is associated with LDV replication in the CNS and
      lung. This animal model may be useful to investigate physiological and molecular
      mechanisms associated with the development of respiratory failure in
      neurodegenerative diseases.

PMID- 11517402
TI  - The biology of JC virus and progressive multifocal leukoencephalopathy.
      Proceedings of a workshop.

PMID- 11517401
TI  - Experimental infection of mice with Borna disease virus (BDV): replication and
      distribution of the virus after intracerebral infection.
AB  - To develop an animal model resembling natural asymptomatic Borna disease virus
      (BDV) infections, BDV He/80 rat brain homogenate was passaged four times in adult
      SJL/J mice. Within 12 months of observation, mice did not develop overt signs of
      disease. Nucleotide sequencing of the rat isolate and the mouse isolates at the
      fourth passage revealed no difference in the deduced amino acids. Viral RNA was
      found in brain, heart, kidney, lung, liver, and urinary bladder. Infectious virus
      was isolated from brain, but also from heart and lung tissue.
      Immunohistochemically, BDV was demonstrated in nerves in the abdominal cavity,
      ganglion coeliacum, and adrenal glands, but not in organ parenchyma.
      Occasionally, viral RNA was detected in mononuclear blood cells.

PMID- 11517403
TI  - A classification scheme for human polyomavirus JCV variants based on the
      nucleotide sequence of the noncoding regulatory region.
AB  - The human polyomavirus JCV is responsible for the central nervous system (CNS)
      demyelination observed in cases of progressive multifocal leukoencephalopathy
      (PML). Lytic infection of oligodendrocytes, the cells that constitute the basis
      of myelin in the CNS, is established by JCV in conjunction with immunosuppressive
      conditions. Beyond this, however, many questions related to JCV pathogenesis
      remain unanswered. The JCV regulatory region is a hypervariable noncoding
      sequence positioned between the early and late protein-coding regions. The
      particular nucleotide sequence of a JCV regulatory region affects levels of viral
      transcription and replication. Modifications to this promoter/enhancer structure
      can alter the cellular host range and may be responsible for switching JCV
      between states of lytic and latent infection. The regulatory region structure
      has, therefore, been used to distinguish JCV variants. Nucleotide sequencing
      studies have uncovered numerous variations of regulatory region structure. Until
      now, however, no inclusive nomenclature existed that linked variants by
      regulatory region structure and/or activity. We have arranged all known variant
      JCV regulatory regions into quadrants according to the integration of particular
      sequence sections and repetition of sequence section groups. This arrangement of
      regulatory regions results in an updated nomenclature that is well-suited for
      describing the relationships between JCV variants. Four distinct structural forms
      (I-S, I-R, II-S, and II-R) are defined along with tissue tropisms. This design
      provides logical connections between the variant regulatory regions and may be
      useful for elucidating crucial steps in JCV pathogenesis.

PMID- 11517404
TI  - Physical and functional interaction between viral and cellular proteins modulate
      JCV gene transcription.
AB  - The lytic phase of JC virus (JCV) appears to be highly complex and remains
      elusive. A growing body of experimental evidence suggests that the regulation of
      JCV gene expression and replication requires, in addition to the presence of
      specific transcription factors, cooperativity between viral and cellular
      regulatory proteins. This cooperativity may be accomplished by physical
      interaction of the participant proteins on and/or off the viral DNA sequence.
      Here, we present evidence of specific physical and functional interaction between
      a cellular factor, YB-1, and the JCV early protein, T-antigen, and showed that
      both proteins play important roles in JCV gene transcription. Additionally, our
      data indicate that YB-1 also functionally interact with another viral protein,
      designated agnoprotein, which is expressed late during the course of infection,
      adding further complexity to the currently known picture on JCV gene regulation.

PMID- 11517405
TI  - Structure and function of JC virus T' proteins.

PMID- 11517406
TI  - Analysis of minimal sequences on JC virus VP1 required for capsid assembly.
AB  - Human JC virus (JCV) belongs to the family of Polyomaviridae. The viral capsid is
      composed of 72 capsomeres. Five VP1 molecules make up a capsomere structure. To
      investigate the minimal sequences on JCV VP1 polypeptide required for capsid
      assembly, the first 12 (Delta N12) and 19 (Delta N19) amino acids at the N
      terminus and the last 16 (Delta C16), 17 (Delta C17), and 31 (Delta C31) amino
      acids at the C-terminus of VP1 were truncated and expressed in E. coli. The VP1
      proteins of Delta N12 and Delta C16 were able to self-assemble into a virus-like
      particle similar to that of wild-type (WT) VP1. However, the mutant proteins of
      Delta N19, Delta C17, and Delta C31 formed a pentameric capsomere structure as
      demonstrated by a 10-50% sucrose gradient centrifugation and electron microscopy.
      These results suggest that the 12 amino-terminal and 16 carboxy-terminal amino
      acids of VP1 are dispensable for the formation of virus-like particles, and
      further truncation at either end of VP1 leads to the loss of this property.

PMID- 11517407
TI  - Distribution and function of JCV agnoprotein.
AB  - JC virus (JCV), the causative agent of progressive multifocal leukoencephalopathy
      (PML), encodes six major proteins including agnoprotein, the function of which is
      unknown. To explore its function, we initially studied the expression and
      localization of agnoprotein in both cultured cells and PML brain using
      immunohistochemical methods. Employing a specific polyclonal antibody,
      agnoprotein was found mostly in the cytoplasm of persistently infected JCI cells
      and in the finely elaborated cytoplasmic processes of oligodendroglial cells in
      PML brain. The immunohistochemistry indicated that the cytoplasm of
      oligodendroglial cells was relatively well-preserved in the demyelinated foci.
      Agnoprotein coprecipitated with tubulin in immunoprecipitation assays and the
      colocalization of agnoprotein with cytoplasmic tubulin was verified by double
      immunostaining with confocal microscopy. Transfection of an agnogene deleted JCV
      Mad1 strain [Mad1(Delta agno)] into the susceptible cell line failed to produce
      not only agnoprotein but also VP1 and large T mRNAs, whereas the wild-type JCV
      Mad1 resulted in the expression of both large T and VP1 mRNAs. The cytoplasmic
      agnoprotein was phosphorylated and when coexpressed with GST-EGFP, was also
      localized in the cytoplasm. Inhibition of protein kinase A by its inhibitor H-89,
      however, reversed the cytoplasmic localization of agnoprotein to the nuclear
      compartment. Our results suggest that JCV agnoprotein may "shuttle" between the
      nucleus and cytoplasm in a phosphorylation-dependent manner during viral
      replication.

PMID- 11517408
TI  - A combination of low-dose chlorpromazine and neutralizing antibodies inhibits the
      spread of JC virus (JCV) in a tissue culture model: implications for prophylactic
      and therapeutic treatment of progressive multifocal leukencephalopathy.
AB  - The human polyomavirus, JCV, is the etiologic agent of a fatal central nervous
      system (CNS) demyelinating disease known as progressive multifocal
      leukoencephalopathy (PML). PML occurs predominantly in immunosuppressed patients
      and remains an intractable complication in AIDS. To date, there are no effective
      therapies to treat PML. We previously demonstrated that the neuroleptic drug,
      chlorpromazine, inhibits the endocytic pathway used by JCV to infect glial cells.
      In this paper, we demonstrate that nontoxic doses of chlorpromazine are effective
      at inhibiting JCV multiplication and spread in a tissue culture model. The
      clinical efficacy of this drug or related compounds in treating PML has not been
      evaluated.

PMID- 11517409
TI  - Immune response in progressive multifocal leukoencephalopathy: an overview.
AB  - Progressive multifocal leukoencephalopathy (PML) is a disease usually occurring
      in immunosuppressed patients. By far the most common underlying immunosuppressive
      illness is the acquired immune deficiency syndrome, accounting for about 85% of
      PML cases currently seen in clinical practice. PML may occur in patients with
      deficits in the humoral and/or cellular immune response such as
      lymphoproliferative diseases, myeloproliferative diseases, carcinomatous diseases
      and acquired immunodeficiency due to autoimmune diseases and immunosuppressive
      therapy. The humoral immune response in PML is indicative of a persistent,
      reactivated infection with a prominent immunoglobulin (lgG) G synthesis to virus
      protein 1 (VP1). An lgM synthesis in serum is rarely found. In about 76% of PML
      cases, an intrathecal humoral immune response to recombinant VP1 can be found as
      compared to only 3.2% in healthy controls. The detection of intrathecally
      synthesized lgG antibodies to VP1 can be used as an additional diagnostic test
      for the diagnosis of PML. The magnitude of the intrathecal humoral immune
      response appears to rise over time and may be associated with a decrease of viral
      load in cerebrospinal fluid (CSF) and possibly the central nervous system (CNS).
      Compared to healthy controls, proliferation of peripheral blood mononuclear cells
      (PBMC) is reduced in PML patients. Immunological studies suggest a general
      impairment of the Th1-type T-helper cell function of cell-mediated immunity.
      Furthermore, the appearance of JCV-specific cytotoxic T-lymphocytes appears to be
      associated with a favorable clinical outcome.

PMID- 11517410
TI  - JCV-specific cellular immune response correlates with a favorable clinical
      outcome in HIV-infected individuals with progressive multifocal
      leukoencephalopathy.
AB  - Most immunosuppressed individuals who develop progressive multifocal
      leukoencephalopathy (PML) have a rapid fatal outcome, whereas some become long
      term survivors. We explored the impact of the cellular immune response against JC
      virus (JCV) on the clinical outcome of 7 HIV+ and 3 HIV- individuals with PML. Of
      the 4 HIV+/PML survivors, all had detectable cytotoxic T lymphocytes (CTL)
      specific for JCV T or VP 1 proteins compared to none of the 3 HIV+/PML
      progressors tested. Of the 3 HIV-/PML patients, 1 was recently diagnosed with PML
      and showed evidence of neurologic improvement without any treatment. This patient
      had CTL specific for the VP1 protein of JCV. The other 2 HIV-/PML survivors were
      stable 3-8 years after the diagnosis of PML. They did not have any detectable CTL
      against JCV. These findings suggest that JCV-specific immune response is
      associated with favorable outcome in HIV+ individuals with PML. The lack of
      detectable JCV-specific CTL in 2 HIV-/PML survivors might indicate a burnt-out
      disease without sufficient antigenic stimulation to maintain the cellular immune
      response. The detection of JCV-specific CTL in an HIV- patient recently diagnosed
      with PML, who was showing evidence of neurological improvement without any
      treatment, indicates that this finding may be used as a favorable prognostic
      marker of disease evolution in the clinical management of patients with PML. As
      the quest for an effective treatment of PML continues, JCV-specific cellular
      immune response deserves further attention because it appears to play a crucial
      role in the prevention of disease progression.

PMID- 11517411
TI  - Epidemiology and prognosis of AIDS-associated progressive multifocal
      leukoencephalopathy in the HAART era.
AB  - Whereas most AIDS-related neurologic disorders have reduced incidence since HAART
      therapy was introduced, we find that the incidence of progressive multifocal
      leukoencephalopathy (PML) did not significantly differ between the pre-HAART and
      the HAART period (OR 0.78; 95% CI 0.41-1.50). These findings were confirmed by
      the preliminary results of the Italian Register Investigative Neuro AIDS (IRINA)
      Study, a prospective multicenter study started in January 2000, which showed that
      PML was the second most frequently diagnosed neurologic disorder after TE. A
      similar proportion of cases were found in HAART-naive and HAART-experienced
      patients in our experience. PML was more common in the presence of HIV RNA > 500
      copies/ml. Most of the cases occurring in HAART-exposed patients developed within
      the first 6 months of therapy. As others have reported, we find a prolonged
      survival in PML subjects prescribed HAART (245 days in the group treated with
      HAART versus 66 days in the group not treated with HAART; P at log rank = 0.001).
      However despite the survival benefit, AIDS-associated PML still has a serious
      prognosis. In fact, PML had the lowest 1-year survival probability of any
      cerebral disorder in our study (P = 0.0005). Our findings also confirm that CSF
      JCV DNA burden at baseline is a useful prognostic indicator with a threshold of
      4.7 log(10) JCV copies/ml (P at log rank = 0.01) in our experience. CSF JCV DNA
      load at 4 weeks of follow-up and clearance of JCV-DNA from CSF are associated
      with a better neurologic outcome and a longer survival.

PMID- 11517413
TI  - Predicted amino acid sequences for 100 JCV strains.
AB  - DNA sequence variation between JCV genotypes is confined largely to noncoding
      intergenic regions and introns. Nevertheless, evidence suggests that the amino
      acid sequence variations among the 8 genotypes of JCV can influence the potential
      for neurovirulence of the virus. In the current study, the amino acid sequences
      for 100 JCV genomes were translated and grouped into genotype families. Subtype
      consensus sequences were determined and the type-specific amino acid sequence
      variants were identified.

PMID- 11517412
TI  - Epidemiological evidence and molecular basis of interactions between HIV and JC
      virus.

PMID- 11517414
TI  - Excretion and transmission of JCV in human populations.
AB  - The potential transmission of JCV through the environment has been analyzed by
      studying the JC viruses present in raw sewage of urban populations from widely
      divergent geographical areas. High numbers of JCV were found. JCV was detected in
      98% (51/52) of sewage samples from different geographical areas in Europe,
      Africa, and USA by applying a Nested-PCR procedure. The mean estimated
      concentration of JCV in sewage was of 10(2)-10(3) viral particles/ml. Sequence
      analysis shows that JCV found in environmental samples present an archetypal
      structure in the regulatory region as it has been described in urine samples.
      Cerebrospinal fluid samples (CSF) of PML (progressive multifocal
      leucoencephalopathy) patients were also analyzed as control samples in this study
      presenting tandem repeats and rearrangements at the regulatory region (RR).
      Sequence analysis of the intergenic region (IGR) allowed the typification and
      phylogenetic analysis of the JCV sequences detected in sewage. JC viral particles
      were also found to be stable in sewage samples at 20 degrees C for more than 70
      days. This data suggest the idea that the intake of water or food contaminated
      with JCV could constitute a portal of entry for the virus or the viral DNA to the
      human organism.

PMID- 11517415
TI  - Challenges for clinical trials on progressive multifocal leukoencephalopathy.

PMID- 11517416
TI  - The relative contributions of HAART and alpha-interferon for therapy of
      progressive multifocal leukoencephalopathy in AIDS.
AB  - To explore the respective roles of highly active antiretroviral therapy (HAART)
      and alpha-interferon in improving survival of patients with AIDS-related PML, we
      retrospectively analyzed all patients with AIDS and PML who were referred to
      Johns Hopkins University HIV Neurology Program from 1985 to 2000. For 97
      evaluable patients, we compared survival of those who were on HAART (three or
      more antiretroviral drugs) to those who were not on HAART. The effect of alpha
      interferon was also studied. Multivariate analysis showed no difference in
      survival among patients on none, one, or two forms of antiretrovirals; however,
      survival was significantly greater for those on HAART. Whereas alpha-interferon
      use was shown to be associated with longer survival (P < 0.057), this effect was
      not independent of the effects of HAART. HAART significantly increases survival
      for patients with PML and AIDS; however, alpha-interferon does not appear to
      provide additional benefit.

PMID- 11517417
TI  - The good and evil of HAART in HIV-related progressive multifocal
      leukoencephalopathy.
AB  - The use of highly active anti-retroviral therapy in patients with HIV-related
      progressive multifocal leukoencephalopathy is associated with increased survival
      and disease stabilization. However, approximately half of the patients receive no
      benefit from these treatments. In a group of HIV-infected patients with
      histologically or virologically confirmed PML, we recognized two distinct
      patterns of response, i.e., long survivors versus nonresponders, but could not
      identify any factors at baseline predictive of PML outcome. In addition, the use
      of cidofovir did not substantially affect survival. However, the survival rate
      was higher during the first years of HAART, i.e., 1996-1997, with better outcomes
      observed in patients receiving a protease inhibitor-containing regimen either
      irregularly or after a switch from a 2-nucleoside reverse transcriptase inhibitor
      combination. In contrast, PML outcome was frequently poor in both HAART-naive and
      -experienced patients who responded promptly to anti-HIV therapy in terms of CD4
      increase and viral load decrease. In addition, in a number of patients, PML onset
      was temporally associated with immune reconstitution. It may be that, in some
      patients, rapid immune reconstitution due to HAART paradoxically worsens the
      course of PML. Gradual reversal of immune deficiency might be associated with
      better outcome.

PMID- 11517418
TI  - Potent anti-retroviral therapy with or without cidofovir for AIDS-associated
      progressive multifocal leukoencephalopathy: extended follow-up of an
      observational study.
AB  - To analyze the clinical efficacy of cidofovir combined with highly active anti
      retroviral therapy (HAART) in AIDS-related progressive multifocal
      leukoencepalopathy (PML), a multicenter observational study was performed.
      Consecutive HIV-positive patients with histologically or virologically proven PML
      and at least 4 weeks of treatment after diagnosis were examined: 27 patients were
      treated with HAART, whereas 16 patients were treated with HAART plus cidofovir 5
      mg/kg intravenously per week for the first 2 weeks and every other week
      thereafter. JC virus DNA was quantified in cerebrospinal fluid (CSF) by PCR.
      Baseline virologic, immunologic, and clinical characteristics as well as HIV RNA
      and CD4 responses to HAART were homogeneous between the groups. The median follow
      up was 132 weeks. In one case (6%), cidofovir was permanently discontinued
      because of severe proteinuria. One-year cumulative probability of survival was
      0.61 with cidofovir and 0.29 without (log rank test P = 0.02). After adjusting
      for baseline CD4 counts, JC viral load in CSF, Karnofsky, and use of HAART prior
      to the onset of PML, the use of cidofovir was independently associated with a
      reduced risk of death (hazard ratio, 0.21, 95% confidence interval, 0.07-0.65; P
      = 0.005). A randomized study will definitively establish whether cidofovir
      confers significant advantage over HAART alone in AIDS-related PML.

PMID- 11517419
TI  - Designs for clinical trials to test the efficacy of therapeutics in progressive
      multifocal leukoencephalopathy.
AB  - The design of a comparative treatment trial to evaluate the efficacy of
      therapeutics for progressive multifocal leukoencephalopathy (PML) is outlined. We
      propose a large simple randomized trial with patient survival as its primary
      endpoint, completed in a short period of time and involving a cohort with as few
      enrollment restrictions as possible. We use stratification as the counterweight
      to the lack of exclusion criteria and suggest that proper stratification will
      attenuate differences inherent in a heterogeneous subject cohort. Estimation of
      power, sample size, and study duration, implementation of interim analyses,
      toxicity management, and validation of secondary clinical measures are also
      addressed.

PMID- 11517420
TI  - Cidofovir in AIDS-associated progressive multifocal leukoencephalopathy: a
      monocenter observational study with clinical and JC virus load monitoring.
AB  - A monocenter observational study was conducted to determine the clinical and
      virological effects of cidofovir added to highly active anti-retroviral therapy
      (HAART) in AIDS-associated progressive multifocal leukoencephalopathy (PML).
      Exposure to other anti-viral drugs or late initiation of cidofovir were exclusion
      criteria. Of the 53 consecutive patients with virologically proven PML admitted
      at the NeuroAIDS Unit of Bicetre Hospital between May 1996 and July 2000 and
      having received HAART with or without cidofovir, 46 met the inclusion criteria.
      Cidofovir was initiated in most cases on compassionate grounds. The 22 patients
      treated with HAART only (HAART group) were compared to the 24 patients treated
      with HAART and cidofovir (CDV group). Survival, neurological outcome assessed by
      the expanded disability status scale (EDSS), and monitoring of the JC virus (JCV)
      load in CSF were investigated prospectively. At baseline (date of initiation or
      intensification of HAART), both groups were similar regarding CD4 cell count,
      plasma HIV load, CSF JCV load, EDSS, and demographic features. Both groups had
      similar response to HAART in terms of plasma HIV load and CD4 cell count. At
      month 6, CSF-JCV load was below the detection level in 8 out of 24 (33%) patients
      from the CDV group and 7 out of 18 (39%) patients from the HAART group (P =
      0.71). One-year cumulative probability of being alive was 62% in the CDV group
      and 53% in the HAART group (P = 0.72). However, an additional benefit with
      respect to survival was observed in patients who were given cidofovir after
      adjustment to the following baseline variables (CSF-JCV load, CD4 cell count, and
      EDSS). Despite the addition of cidofovir to HAART, no significant benefit had
      been observed in neurological outcome, particularly in patients with an early
      worsening.

PMID- 11517421
TI  - Convection-enhanced intraparenchymal delivery (CEID) of cytosine arabinoside
      (AraC) for the treatment of HIV-related progressive multifocal
      leukoencephalopathy (PML).
AB  - AIDS-related PML continues to be a relatively common and rapidly fatal infection
      in patients with AIDS, and no effective therapy has been established to alleviate
      the effects of this disease. Through the years, isolated reports and small case
      studies have shown somewhat encouraging results using cytosine arabinoside (AraC)
      in the treatment of PML. The optimism behind the use AraC for this disease began
      to fade with ACTG trial 243, which suggested that AraC had no benefit in patients
      with HIV-related PML. In this article, we provide evidence that suggests that the
      failure of AraC in the ACTG trial may have been due to insufficient delivery of
      the drug through traditional intravenous and intrathecal routes. Furthermore, we
      provide evidence that convection-enhanced intraparenchymal delivery of AraC may
      prove to be a safe and effective means of treating this infection, and we outline
      a clinical trial that we have recently undertaken to test this hypothesis.

PMID- 11517422
TI  - Treatment of non-AIDS progressive multifocal leukoencephalopathy with cytosine
      arabinoside.
AB  - This open label study determined the outcome of non-AIDS progressive multifocal
      leukoencephalopathy patients treated with a standard dose of intravenous cytosine
      arabinoside. Nineteen patients with PML proven by brain biopsy or spinal fluid
      polymerase chain reaction were treated with intravenous cytosine arabinoside 2
      mg/kg per day for 5 days and followed for neurologic outcome by neurologic
      examination and MRI scanning. Seven of 19 PML patients treated with cytosine
      arabinoside intravenously improved neurologically. The range of follow-up for
      these patients was 2.0 to 4.5 years. All were left with neurologic deficits but
      were functionally improved, and 6 of 7 were able to independently carry out the
      activities of daily living. Twelve PML patients showed no evidence of response
      and died rapidly of their disease after treatment (range, 8 days to 6 months).
      All who survived their neurologic disease recovered from treatment-induced
      pancytopenia. Cytosine arabinoside given intravenously to non-AIDS PML patients
      in this small study was associated with a 36% chance of developing stabilization
      at 1 year. Treatment was associated with significant bone marrow toxicity. The
      improvement in MRI scan changes in those patients who responded took 6 weeks or
      longer.

PMID- 11517423
TI  - A signal, from human mtDNA, of postglacial recolonization in Europe.
AB  - Mitochondrial HVS-I sequences from 10,365 subjects belonging to 56
      populations/geographical regions of western Eurasia and northern Africa were
      first surveyed for the presence of the T-->C transition at nucleotide position
      16298, a mutation which has previously been shown to characterize haplogroup V
      mtDNAs. All mtDNAs with this mutation were then screened for a number of
      diagnostic RFLP sites, revealing two major subsets of mtDNAs. One is haplogroup V
      proper, and the other has been termed "pre*V," since it predates V
      phylogenetically. The rather uncommon pre*V tends to be scattered throughout
      Europe (and northwestern Africa), whereas V attains two peaks of frequency: one
      situated in southwestern Europe and one in the Saami of northern Scandinavia.
      Geographical distributions and ages support the scenario that pre*V originated in
      Europe before the Last Glacial Maximum (LGM), whereas the more recently derived
      haplogroup V arose in a southwestern European refugium soon after the LGM. The
      arrival of V in eastern/central Europe, however, occurred much later, possibly
      with (post-)Neolithic contacts. The distribution of haplogroup V mtDNAs in modern
      European populations would thus, at least in part, reflect the pattern of
      postglacial human recolonization from that refugium, affecting even the Saami.
      Overall, the present study shows that the dissection of mtDNA variation into
      small and well-defined evolutionary units is an essential step in the
      identification of spatial frequency patterns. Mass screening of a few markers
      identified using complete mtDNA sequences promises to be an efficient strategy
      for inferring features of human prehistory.

PMID- 11517424
TI  - An immune defect causing dominant chronic mucocutaneous candidiasis and thyroid
      disease maps to chromosome 2p in a single family.
AB  - We describe a large family in which a combination of chronic mucocutaneous
      candidiasis (fungal infections of the skin, nails, and mucous membranes) and
      thyroid disease segregate as an autosomal dominant trait with reduced penetrance.
      The family includes (a) four members with both candidiasis and thyroid disease,
      (b) five members, including one pair of phenotype-concordant MZ twins, with
      candidiasis only, and (c) three members with thyroid disease only. A whole-genome
      scan using DNA samples from 20 members of the family identified a candidate
      linkage region on chromosome 2p. By sampling additional individuals and
      genotyping supplementary markers, we established linkage to a region of
      approximately 15 cM bounded by D2S367 and D2S2240 and including seven adjacent
      markers consistent with linkage. With a penetrance estimate of.8, which was based
      on pedigree and affected status, the peak two-point LOD score was 3.70 with
      marker D2S2328, and the peak three-point LOD score was 3.82. This is the first
      linkage assignment of a dominant locus for mucocutaneous candidiasis.

PMID- 11517425
TI  - The Ising model in physics and statistical genetics.
AB  - Interdisciplinary communication is becoming a crucial component of the present
      scientific environment. Theoretical models developed in diverse disciplines often
      may be successfully employed in solving seemingly unrelated problems that can be
      reduced to similar mathematical formulation. The Ising model has been proposed in
      statistical physics as a simplified model for analysis of magnetic interactions
      and structures of ferromagnetic substances. Here, we present an application of
      the one-dimensional, linear Ising model to affected-sib-pair (ASP) analysis in
      genetics. By analyzing simulated genetics data, we show that the simplified Ising
      model with only nearest-neighbor interactions between genetic markers has
      statistical properties comparable to much more complex algorithms from genetics
      analysis, such as those implemented in the Allegro and Mapmaker-Sibs programs. We
      also adapt the model to include epistatic interactions and to demonstrate its
      usefulness in detecting modifier loci with weak individual genetic contributions.
      A reanalysis of data on type 1 diabetes detects several susceptibility loci not
      previously found by other methods of analysis.

PMID- 11517426
TI  - Influenza vaccine effectiveness in preventing hospitalizations and deaths in
      persons 65 years or older in Minnesota, New York, and Oregon: data from 3 health
      plans.
AB  - This study developed methods and determined the impact of influenza vaccination
      on elderly persons in 3 large health plans: Kaiser Permanente Northwest,
      HealthPartners, and Oxford Health Plans. Data for the 1996-1997 and 1997-1998
      seasons were extracted from administrative databases. Subjects were health plan
      members > or = 65 years old. Comorbid conditions collected from the preceding
      year were used for risk adjustment with logistic regression. The virus-vaccine
      match was excellent for year 1 and fair for year 2. Both years, during peak and
      total periods, vaccination reduced all causes of death and hospitalization for
      pneumonia and influenza: hospitalizations were reduced by 19%-20% and 18%-24% for
      years 1 and 2, respectively, and deaths were reduced by 60%-61% and 35%-39% for
      the same periods. These results show that all elderly persons should be immunized
      annually for influenza. The methods used in this study are an efficient cost
      effective way to study vaccine impact and similar questions.

PMID- 11517427
TI  - Tissue dynamics of CD8 lymphocytes that suppress viral replication in cats
      infected neonatally with feline immunodeficiency virus.
AB  - The purpose of this study was to determine the tissue distribution and antiviral
      activity of the CD8 lymphocytes that suppress the replication of feline
      immunodeficiency virus (FIV). Cell-associated FIV load, CD8alpha(+)beta(low)
      cells, and CD8 cell-mediated suppression of FIV were measured serially in the
      blood, thymus, and peripheral lymph nodes after neonatal inoculation. Between 6
      and 10 weeks, relative numbers of CD8alpha(+)beta(low) cells increased, whereas
      CD8alpha(+)beta(high) cells declined in the thymus and blood of infected cats. By
      12-16 weeks, the lymph nodes were enlarged because of an absolute expansion of
      all CD8beta subpopulations. The strength of CD8 cell-mediated FIV suppression in
      vitro, but not CD8alpha(+)beta(low) cell content, was correlated inversely with
      virus load in the thymus and blood. Thus, after neonatal FIV inoculation,
      CD8alpha(+)beta(low) cells first occupy the thymus and blood, where strong CD8
      cell-mediated antiviral activity is linked to reduced virus load in multiple
      lymphoid tissues.

PMID- 11517428
TI  - Prevalence, incidence, and type-specific persistence of human papillomavirus in
      human immunodeficiency virus (HIV)-positive and HIV-negative women.
AB  - Human immunodeficiency virus (HIV) infection and related immunosuppression are
      associated with excess risk for cervical neoplasia and human papillomavirus (HPV)
      persistence. Type-specific HPV infection was assessed at 6-month intervals for
      HIV-positive and HIV-negative women (median follow-up, 2.5 and 2.9 years,
      respectively). The type-specific incidence of HPV infection was determined, and
      risk factors for HPV persistence were investigated by statistical methods that
      accounted for repeated measurements. HIV-positive women were 1.8, 2.1, and 2.7
      times more likely to have high-, intermediate-, and low-risk HPV infections,
      respectively, compared with HIV-negative women. In multivariate analysis, high
      viral signal, but not viral risk category, was independently associated with
      persistence among HIV-positive subjects (odds ratio [OR], 2.5; 95% confidence
      interval [CI], 2.1-2.9). Furthermore, persistence was 1.9 (95% CI, 1.5-2.3) times
      greater if the subject had a CD4 cell count <200 cells/microL (vs. >500
      cells/microL). Thus, HIV infection and immunosuppression play an important role
      in modulating the natural history of HPV infection.

PMID- 11517429
TI  - Human immunodeficiency virus type 1 envelope-stimulated interleukin-2 production
      and survival of infected children with severe and mild clinical disease.
AB  - Interleukin (IL)-2 production after stimulation with human immunodeficiency virus
      type 1 (HIV-1) envelope (Env) peptides, tetanus toxoid, and phytohemagglutinin
      was measured in peripheral blood mononuclear cells (PBMC) from 25 HIV-1-infected
      children with mild and 24 with severe clinical disease and from 15 uninfected
      children. Env-specific IL-2 production was detected in PBMC of 26.5% of HIV-1
      infected children but in none of the uninfected. The absence of Env-specific
      responses at enrollment among infected children was associated with a 6-fold
      increased risk of mortality within a year, adjusting for clinical severity
      (P=.04). Among those with severe clinical disease, Env-stimulated IL-2 reactivity
      in PBMC was negatively correlated with HIV-1 RNA copy numbers in plasma at
      enrollment and was positively correlated with CD4 T cell percentages 1 year
      later. HIV-specific cellular immune responses may play a role in containing
      progression of HIV-1 infection in children, despite early deficits in cell
      mediated immunity.

PMID- 11517430
TI  - Plasma levels of soluble CD14 and tumor necrosis factor-alpha type II receptor
      correlate with cognitive dysfunction during human immunodeficiency virus type 1
      infection.
AB  - The relationship between monocyte immune responses and cognitive impairment
      during progressive human immunodeficiency virus type 1 (HIV-1) infection was
      investigated in 28 subjects receiving highly active antiretroviral therapy. The
      mean+/-SEM CD4(+) T lymphocyte count and virus load for all patients were 237+/
      41 cells/mm(3) and 77,091+/-195,372 HIV-1 RNA copies/mL, respectively. Levels of
      soluble tumor necrosis factor-alpha type II receptor (sTNF-RII) and soluble CD14
      (sCD14) were measured in plasma by ELISA and were correlated with results from
      neuropsychological, magnetic resonance imaging, and magnetic resonance
      spectroscopy tests. Plasma sCD14 and sTNF-RII levels were elevated in subjects
      with cognitive impairment and in those with brain atrophy. Furthermore, both
      factors were correlated with spectroscopic choline:creatine ratios. These
      findings support the idea that peripheral immune responses are linked to
      cognitive dysfunction during advanced HIV-1 disease.

PMID- 11517431
TI  - Inconsistent reconstitution of cytomegalovirus-specific cell-mediated immunity in
      human immunodeficiency virus-infected patients receiving highly active
      antiretroviral therapy.
AB  - Cytomegalovirus (CMV)-immune recovery was characterized in human immunodeficiency
      virus (HIV)-infected patients receiving highly active antiretroviral therapy. CMV
      lymphocyte proliferation (LP), responder-cell frequency (RCF), and interferon
      (IFN)-gamma and interleukin (IL)-2 secretion were studied in CMV-seropositive HIV
      infected patients and in CMV-seropositive HIV-uninfected control subjects. HIV
      infected patients and control subjects had similar proportions of IL-2 and IFN
      gamma, but levels were lower in HIV-infected patients. LP and RCF were
      significantly less frequent and of lower magnitude in HIV-infected patients. The
      measures of CMV cell-mediated immunity were correlated in HIV-uninfected but not
      in HIV-infected subjects. To investigate this, IL-2, IL-12, anti-CD28 plus anti
      CD49d, or anti-IL-10 was added in vitro, with no effect on LP. However, CD8 cell
      depletion of mononuclear cells from HIV-infected patients increased LP responses
      to levels similar to those of uninfected control subjects; before depletion, only
      RCF correlated with CD4 cell counts, but after depletion, LP also correlated with
      CD4 cell counts.

PMID- 11517432
TI  - Immune-mediated phagocytosis and killing of Streptococcus pneumoniae are
      associated with direct and bystander macrophage apoptosis.
AB  - Apoptosis of macrophages may be a pathogen-directed mechanism of immune escape or
      may represent appropriate host response to infection. Human monocyte-derived
      macrophages (MDMs) from healthy donors (C-MDMs) exhibited low-level constitutive
      apoptosis, but culture of MDMs with opsonized serotype I Streptococcus pneumoniae
      (I-MDMs) for 20 h resulted in significantly increased apoptosis. I-MDM apoptosis
      was associated with phagocytosis of bacteria and intracellular killing that was
      blocked by the caspase inhibitor z-VAD-fmk but not by Fas-blocking antibody.
      Paraformaldehyde-fixed I-MDMs induced apoptosis in uninfected syngeneic monocytes
      at levels greater than those in monocytes incubated alone or incubated with fixed
      C-MDMs. Apoptosis of syngeneic monocytes was blocked by anti-Fas antibody. The
      immune response of macrophages to S. pneumoniae includes a novel form of
      apoptosis that is associated with successful phagocytosis and bacterial killing.
      This response in vivo may regulate the inflammatory response to infection during
      a successful host response against S. pneumoniae.

PMID- 11517433
TI  - Streptococcal pyrogenic exotoxin B enhances tissue damage initiated by other
      Streptococcus pyogenes products.
AB  - This study compared the pathology and infection pattern of streptococcal
      pyrogenic exotoxin B-positive (SpeB(+)) and SpeB-negative (SpeB(-)) isogenic
      variants of an M1 isolate of Streptococcus pyogenes in a mouse skin air sac
      model. SpeB(+) strains resulted in severe local tissue damage that extended from
      the epidermis through the subcutaneous layers, whereas isogenic SpeB(-) variants
      had reduced gross pathology. At the histologic level, differences in necrosis and
      host responses to each variant were apparent. Injection of purified SpeB alone
      into a skin air sac failed to induce any significant tissue damage; however,
      coinjection of the enzyme with either the wild-type or the speB mutant resulted
      in increased and accelerated tissue necrosis. Surprisingly, coinjection of the
      enzyme with the spleen-recovered SpeB(-) variant failed to induce a lesion.

PMID- 11517434
TI  - Differential role of cytosolic phospholipase A2 in the invasion of brain
      microvascular endothelial cells by Escherichia coli and Listeria monocytogenes.
AB  - Invasion of brain microvascular endothelial cells (BMECs) is a key step in the
      pathogenesis of meningitis due to Escherichia coli and Listeria monocytogenes.
      Although host cell actin cytoskeletal rearrangements are essential in BMEC
      invasion by E. coli K1 and L. monocytogenes, the underlying signaling mechanisms
      remain unclear. This study demonstrates that host cell cytosolic phospholipase A2
      (cPLA2) contributes to E. coli K1 invasion of BMECs but not to L. monocytogenes
      invasion of BMECs. This difference was observed with 4-bromophenacyl bromide, a
      nonselective PLA2 inhibitor, and arachidonyl trifluoromethyl ketone, a selective
      cPLA2 inhibitor, and was confirmed with BMEC derived from cPLA2 knockout mice.
      Activation of cPLA2 leads to generation of intracellular arachidonic acid, which
      is metabolized via cyclooxygenase (COX) and lipo-oxygenase (LOX) pathways into
      eicosanoids. COX and LOX inhibitors also significantly inhibit E. coli K1
      invasion of BMECs.

PMID- 11517435
TI  - Efficacy of postinfection treatment with anti-Shiga toxin (Stx) 2 humanized
      monoclonal antibody TMA-15 in mice lethally challenged with Stx-producing
      Escherichia coli.
AB  - Infection with Shiga toxin (Stx)-producing Escherichia coli (STEC) causes
      hemorrhagic colitis and hemolytic uremic syndrome. TMA-15 is a humanized
      monoclonal antibody against Stx2, a major pathogenic factor. In a mouse infection
      model that used B2F1, a virulent STEC strain, the efficacy of TMA-15 was assessed
      when it was administered after bacterial and toxin exposure. In this model, a
      time-course analysis of the serum Stx2 level showed that the toxin was detectable
      from 24 h after infection. In an evaluation of the time-dependent efficacy,
      treatment with TMA-15 up to 24 h after infection ameliorated the lethal
      challenge, although treatment at 48 h showed no efficacy. To determine the
      effective dose, escalating doses were administered at 24 h after infection. The
      number of mice that survived after doses of 0, 0.25, 0.5, 1.0, and 2.0 mg/kg were
      0/20, 11/20, 17/20, 20/20, and 20/20, respectively. These findings suggest that
      TMA-15 shows potential for prevention of severe complications associated with
      STEC infection.

PMID- 11517436
TI  - Cadaverine prevents the escape of Shigella flexneri from the phagolysosome: a
      connection between bacterial dissemination and neutrophil transepithelial
      signaling.
AB  - Shigella flexneri causes bacillary dysentery in humans by invading epithelial
      cells of the colon, which is characterized by an acute polymorphonuclear
      leukocyte (PMNL)-rich inflammation. Our recent studies demonstrated that
      cadaverine, a polyamine, specifically acts to abrogate transepithelial signaling
      to PMNL induced by S. flexneri. Here, insight is provided into the cellular
      mechanisms by which cadaverine attenuates the ability of Shigella species to
      induce PMNL signaling. It was found that cadaverine retards the lysis of the
      Shigella species-containing vacuole, suggesting that a blockade is established,
      in which the pathogen is prevented from adequately interacting with the
      cytoskeleton. Furthermore, an IcsA mutant of S. flexneri that cannot interact
      with the cytoskeleton and spreads intercellularly fails to induce transmigration
      of PMNL. Results indicate that cadaverine-induced compartmentalization of
      Shigella species to the phagolysosome might be a protective response of the host
      that directly contributes to the diminished ability of PMNL to transmigrate
      across model intestinal epithelia.

PMID- 11517437
TI  - Nosocomial outbreak of Microbacterium species bacteremia among cancer patients.
AB  - To date, only 6 sporadic Microbacterium species (formerly coryneform Centers for
      Disease Control and Prevention [CDC] groups A-4 and A-5) infections have been
      reported. The source, mode of transmission, morbidity, mortality, and potential
      for nosocomial transmission of Microbacterium species remain unknown. From 26
      July through 14 August 1997, 8 episodes of coryneform CDC group A-5 symptomatic
      bacteremia occurred in 6 patients on the oncology ward at the Maine Medical
      Center. One patient died. All isolates were identified at CDC as Microbacterium
      species and had identical DNA banding patterns by pulsed-field gel
      electrophoresis. To assess risk factors for Microbacterium species infection, a
      retrospective cohort study was conducted. The presence of a central venous
      catheter was the strongest risk factor (6/6 vs. 22/48; relative risk, 3.2;
      P<.0001). This outbreak demonstrates significant Microbacterium species
      associated morbidity and mortality in immunocompromised populations and confirms
      the potential for epidemic nosocomial transmission.

PMID- 11517438
TI  - Effects of ethanol on NF-kappaB activation, production of myeloid growth factors,
      and adhesive events in human endothelial cells.
AB  - Because neutropenia may aggravate infections in alcoholics, effects of ethanol on
      the generation of myeloid growth factors by human umbilical vein endothelial
      cells (HUVECs) and on interactions with neutrophils were examined in vitro.
      Exposure of HUVECs to ethanol (0.01%-1%) dose-dependently inhibited (by 12%-27%)
      the release of stem cell factor, granulocyte-macrophage and granulocyte colony
      stimulating factors (CSFs), or interleukin (IL)-8, but not of macrophage CSF
      triggered by lipopolysaccharide (LPS) or IL-1. Ethanol also inhibited the LPS
      induced increase in HUVECs to bind neutrophils by 28% (without affecting the
      expression of intracellular adhesion molecule-1 and E-selectin) and inhibited the
      translocation of the p65 subunit of NF-kappaB from the cytoplasm to the nucleus
      by 46%. Thus, exposure of HUVECs to ethanol inhibited the generation of cytokines
      important for myeloid cell development and reduced the adhesiveness of HUVECs for
      neutrophils: effects that are possibly linked to the reduced activation of NF
      kappaB.

PMID- 11517439
TI  - Chloroquine-resistant malaria.
AB  - The development of chloroquine as an antimalarial drug and the subsequent
      evolution of drug-resistant Plasmodium strains had major impacts on global public
      health in the 20th century. In P. falciparum, the cause of the most lethal human
      malaria, chloroquine resistance is linked to multiple mutations in PfCRT, a
      protein that likely functions as a transporter in the parasite's digestive
      vacuole membrane. Rapid diagnostic assays for PfCRT mutations are already
      employed as surveillance tools for drug resistance. Here, we review recent field
      studies that support the central role of PfCRT mutations in chloroquine
      resistance. These studies suggest chloroquine resistance arose in > or = 4
      distinct geographic foci and substantiate an important role of immunity in the
      outcomes of resistant infections after chloroquine treatment. P. vivax, which
      also causes human malaria, appears to differ from P. falciparum in its mechanism
      of chloroquine resistance. Investigation of the resistance mechanisms and of the
      role of immunity in therapeutic outcomes will support new approaches to drugs
      that can take the place of chloroquine or augment its efficiency.

PMID- 11517440
TI  - Susceptibility to primary Epstein-Barr virus infection is associated with
      interleukin-10 gene promoter polymorphism.
AB  - In total, 116 children were investigated to determine whether the interleukin
      (IL)-10 polymorphism influences the age at primary Epstein-Barr virus (EBV)
      infection. The promoter of IL-10 is polymorphic, with 3 known single base
      substitutions (G/A at -1082, C/T at -819, and C/A at -592), which form 3
      haplotypes: GCC, ACC, and ATA. This study found that carriage of the ATA
      haplotype protects against early EBV infection. The presence of the ATA haplotype
      was associated with EBV seronegativity (odds ratio, 2.6; 95% confidence interval,
      1.04-6.7; P=.04), when controlled by age. To examine the effect of haplotypes on
      IL-10 production, IL-10 plasma levels were measured in 50 newborns and 400 adults
      and were correlated with the IL-10 haplotype. The IL-10 levels were significantly
      higher in the ATA carriers than in the noncarriers. These data suggest that the
      IL-10 ATA haplotype confers protection against primary EBV infection and that the
      effect is mediated by high IL-10 levels.

PMID- 11517441
TI  - Comparison of genotypic and phenotypic resistance patterns of human
      immunodeficiency virus type 1 isolates from patients treated with stavudine and
      didanosine or zidovudine and lamivudine.
AB  - Sequencing of reverse-transcriptase genes and recombinant virus assays were
      performed on paired isolates from antiretroviral drug-naive patients randomized
      to stavudine and didanosine (group 1; n = 21) or zidovudine and lamivudine (group
      2; n = 21) at baseline and after > or = 12 months of follow-up. The T215Y
      mutation emerged in 13 (61.9%) and 2 (9.5%) isolates in groups 1 and 2,
      respectively (P < .0001). Furthermore, in group 1, mutations associated with
      multidideoxynucleoside resistance were selected in 3 isolates. In group 2, all
      isolates carried the M184V mutation. The median fold changes in susceptibilities
      to zidovudine, stavudine, and lamivudine were 16.4 and 1, 2.2 and 0.6, and 4.5
      and > 38 in groups 1 and 2, respectively (P < .0001, all comparisons). These
      results suggest that the combination of stavudine and didanosine is associated
      more frequently with the emergence of zidovudine resistance and a decrease in
      susceptibility to stavudine than the combination of zidovudine and lamivudine.

PMID- 11517442
TI  - Prevalence of Rho-inactivating epidermal cell differentiation inhibitor toxins in
      clinical Staphylococcus aureus isolates.
AB  - Staphylococcus aureus produces exotoxins of the epidermal cell differentiation
      inhibitor (EDIN) family that ADP-ribosylate and inactivate Rho GTPases. The
      prevalence of genes encoding EDIN in clinical and nasal isolates of S. aureus was
      investigated. Of the 196 clinical S. aureus isolates tested, 15 (7.8%) were
      positive for 1 edin gene, whereas of 81 nasal isolates tested, only 3 (3.7%) were
      edin positive. Of the total 18 edin-positive isolates, 16 (90%) carried edin-B
      and 2 (10%) carried edin-C, but none was positive for edin-A. All edin-positive
      strains could produce the respective EDIN protein. Pulsed-field gel
      electrophoresis analysis suggested that the edin-B-positive S. aureus isolates
      are derived from one clone, and the edin-C-positive isolates are derived from
      another clone. Given that toxins acting on Rho GTPases are considered to be
      important for bacterial virulence, the EDIN toxins of S. aureus should receive
      more attention in future studies.

PMID- 11517443
TI  - Cross-reactivity of antibodies to type 6B and 6A polysaccharides of Streptococcus
      pneumoniae, evoked by pneumococcal conjugate vaccines, in infants.
AB  - Streptococcus pneumoniae serotypes 6B and 6A are important causes of infections,
      yet only 6B is included in current vaccines. It is, therefore, crucial to
      evaluate whether functional antibodies are produced against both types after
      vaccination. Concentration and opsonophagocytic activity (OPA) of antibodies to
      6B and 6A polysaccharides were determined in serum samples from infants immunized
      with 3 different pneumococcal conjugate vaccines containing serotype 6B. In all
      vaccine groups, a significant correlation was found between the anti-6B and -6A
      antibody concentration and OPA. However, OPA to the vaccine serotype was
      detectable more commonly than OPA to the cross-reactive type. Furthermore, 5%-15%
      of the serum samples showed high OPA against the 6B but not the 6A strain. On
      average, 2-6 times more anti-6B antibodies were needed for 50% opsonophagocytic
      killing of the type 6A than the type 6B strain. Although pneumococcal type 6B
      conjugate vaccines elicit antibodies that cross-react with type 6A, not all anti
      6B antibodies are functionally cross-reactive.

PMID- 11517444
TI  - Fluoroquinolone-resistant Streptococcus pneumoniae associated with levofloxacin
      therapy.
AB  - Fluoroquinolone-resistant cultures of Streptococcus pneumoniae were isolated from
      2 patients who were treated for pneumonia with levofloxacin. Nucleotide sequence
      analysis of bacterial DNA showed that the isolates contained mutations in both
      parC (DNA topoisomerase IV) and gyrA (DNA gyrase), which were shown previously to
      confer fluoroquinolone resistance. With the resistant isolates, the MICs for
      ciprofloxacin, gatifloxacin, grepafloxacin, levofloxacin, and trovafloxacin were
      above the maximal serum drug concentrations reported for standard dosage
      regimens. In contrast, the MICs for gemifloxacin and moxifloxacin were below the
      maximal serum concentrations. Increased effectiveness at blocking the growth of
      resistant mutants should make gemifloxacin and moxifloxacin less likely to allow
      the enrichment of mutants within susceptible populations. Additional resistance
      mutations in the isolates were readily obtained by plating on gemifloxacin- or
      moxifloxacin-containing agar. Thus, neither compound is expected to halt further
      accumulation of resistance mutations once mutant enrichment has been initiated by
      less potent derivatives.

PMID- 11517445
TI  - Cholera in the United States, 1995-2000: trends at the end of the twentieth
      century.
AB  - To evaluate recent trends in cholera in the United States, surveillance data from
      all cases of laboratory-confirmed toxigenic Vibrio cholerae O1 and O139 infection
      reported to the Centers for Disease Control and Prevention between 1995 and 2000
      were reviewed. Sixty-one cases of cholera, all caused by V. cholerae O1, were
      reported. There was 1 death, and 35 (57%) of the patients were hospitalized.
      Thirty-seven (61%) infections were acquired outside the United States; 14 (23%)
      were acquired through undercooked seafood consumed in the United States, 2 (3%)
      were acquired through sliced cantaloupe contaminated by an asymptomatically
      infected food handler, and no source was identified for 8 (13%) infections. The
      proportion of travel-associated infections resistant to trimethoprim
      sulfamethoxazole, sulfisoxazole, streptomycin, and furazolidone increased from 7
      (8%) of 88 in 1990-1994 to 11 (31%) of 35 in 1995-2000. Foreign travel and
      undercooked seafood continue to account for most US cholera cases. Antimicrobial
      resistance has increased among V. cholerae O1 strains isolated from ill
      travelers.

PMID- 11517446
TI  - Enteropathogenic Escherichia coli and ulcerative colitis in cotton-top tamarins
      (Saguinus oedipus).
AB  - The cotton-top tamarin (CTT; Saguinus oedipus) is an endangered New World primate
      that develops a highly prevalent idiopathic colitis resembling human ulcerative
      colitis. This study found that enteropathogenic Escherichia coli (EPEC) caused
      acute colitis in CTTs, which was associated with ulcerative colitis. EPEC
      clinical isolates revealed localized adherence patterns by HEp-2 assay and were
      devoid of Shiga-toxin production. Sequencing of the eae gene (GenBank accession
      no. AF319597) revealed 99.2% identity to sequences of human isolates (GenBank
      AF116899) and corresponded to the epsilon intimin gene subtype. Detection of
      intimin sequences by polymerase chain reaction on primary fecal cultures
      indicated widespread EPEC infection in the CTT colony. Prospective analysis
      revealed that animals with fecal cultures positive for intimin sequences had a
      higher frequency of active colitis (75.0% vs. 27.2%; P<.005, chi(2) test) and
      higher histological scores of colonic inflammation (0.875 vs. 0.455,
      respectively; P<.05, Mann-Whitney rank sum test).

PMID- 11517447
TI  - Hindlimb asymmetry reduces escape performance in the lizard Psammodromus algirus.
AB  - Locomotor performance of lizards and its relationship to the ecology and
      morphology of the forms concerned has been well studied recently. Asymmetry of
      limbs might make the body unstable and make performance less effective. However,
      their effects on terrestrial locomotion remain almost unexplored. In this
      article, the escape performance of the lizard Psammodromus algirus running at
      high speed was related to hindlimb morphology and fluctuating asymmetry levels.
      Femur length was significantly shorter than crus length. However, absolute
      fluctuating asymmetry in femur length was significantly larger than in crus
      length. Asymmetry was not related to body or limb size, thus larger individuals
      or those with longer limbs did not have significantly greater fluctuating
      asymmetry. Neither body size nor the length of the limbs (femur or crus) were
      significantly related to any of the variables describing escape performance.
      However, escape performance was affected by femur-length fluctuating asymmetry,
      which resulted in significantly reduced overall escape speeds. In contrast,
      asymmetry in crus length did not affect escape performance. We discuss the
      possible basis of these alterations of locomotion, the relevance of reduced
      performance for the ecology of this species, and how individuals may compensate
      for the costs of asymmetry.

PMID- 11517448
TI  - Lizards, lipids, and dietary links to animal function.
AB  - Our experiments were designed to test the hypotheses that dietary lipids can
      affect whole-animal physiological processes in a manner concordant with changes
      in the fluidity of cell membranes. We measured (1) the lipid composition of five
      tissues, (2) body temperatures selected in a thermal gradient (T(sel)), (3) the
      body temperature at which the righting reflex was lost (critical thermal minimal
      [CTMin]), and (4) resting metabolic rate (RMR) at three body temperatures in
      desert iguanas (Dipsosaurus dorsalis) fed diets enriched with either saturated or
      unsaturated fatty acids. The composition of lipids in tissues of the lizards
      generally reflected the lipids in their diets, but the particular classes and
      ratios of fatty acids varied among sampled organs, indicating the conservative
      nature of some tissues (e.g., brain) relative to others (e.g., depot fat).
      Lizards fed the diet enriched with saturated fatty acids selected warmer
      nighttime body temperatures than did lizards fed a diet enriched with unsaturated
      fatty acids. This difference is concordant with the hypothesis that the
      composition of dietary fats influences membrane fluidity and that ectotherms may
      compensate for such changes in fluidity by selecting different body temperatures.
      The CTMin of the two treatment groups was indistinguishable. This may reflect the
      conservatism of some tissues (e.g., brain) irrespective of diet treatment. The
      RMR of the saturated treatment group nearly doubled between 30 degrees and 40
      degrees C. Here, some discrete membrane domains in the lizards fed the saturated
      diet may have been in a more-ordered phase at 30 degrees C and then transformed
      to a less-ordered phase at 40 degrees C. In contrast, the RMR of the unsaturated
      treatment group exhibited temperature independence in metabolic rate from 30
      degrees to 40 degrees C. Perhaps the unsaturated diet resulted in membranes that
      developed a higher degree of disorder (i.e., a certain phase) at a lower
      temperature than were membranes of lizards fed the saturated diet. Our study
      demonstrates links between dietary fats and whole-animal physiology; however, the
      mechanistic basis of these links, and the general knowledge of lipid metabolism
      in squamate reptiles, remain poorly understood and warrant further study.

PMID- 11517449
TI  - Interactive effects of rearing temperature and oxygen on the development of
      Drosophila melanogaster.
AB  - Although higher temperatures strongly stimulate ectothermic metabolic rates, they
      only slightly increase oxygen diffusion rates and decrease oxygen solubility.
      Consequently, we predicted that insect gas exchange systems would have more
      difficulty meeting tissue oxygen demands at higher temperatures. In this study,
      Drosophila melanogaster were reared from egg to adult in hyperoxic (40%), hypoxic
      (10%), and normoxic (21%) conditions and in temperatures ranging from 15 degrees 
      31.5 degrees C to examine the interactive effect of temperature and oxygen on
      development. Hyperoxia generally increased mass and growth rate at higher rearing
      temperatures. At lower rearing temperatures, however, hyperoxia had a very small
      effect on mass, did not affect growth rate, and lengthened time to eclosion.
      Relative to normoxia, flies reared in hypoxic conditions were generally smaller
      (mass and thorax length), had longer eclosion times, slower growth rates, and
      reduced survival. At cooler temperatures, hypoxia had relatively modest or
      nonsignificant effects on development, while at higher temperatures, the effects
      of hypoxia were large. These results suggest that higher temperatures reduce
      oxygen delivery capacity relative to tissue oxygen needs, which may partially
      explain why ectotherms are smaller when development occurs at higher
      temperatures.

PMID- 11517450
TI  - Possible roles for corticosterone and critical size in the fledging of nestling
      pied flycatchers.
AB  - Our study was designed to see whether corticosterone (B) rises abruptly in the
      blood of nestling pied flycatchers (Ficedula hypoleuca) at the time they fledge,
      as reported recently for kestrels, and if so, why. We measured the growth and
      blood levels of B and selected nutrients of nestlings in broods of five, seven,
      and nine chicks during 1998 and 1999. In half of the broods, we clipped selected
      wing and tail feathers of both parents with the intention of making it more
      difficult for them to provide their chicks with food. We collected blood samples
      when the chicks were six to 10 d old (period of rapid growth) and 15 d of age or
      older (0-5 d before fledging). B increased substantially several days before the
      chicks left the nest and then declined somewhat. We found no differences in rates
      of growth or blood levels of B, nutrients, and hematocrit as a function of either
      brood size or parental handicapping. Nestlings within a day of fledging appear to
      have been food deprived in 1998; their glucose was significantly reduced, and B,
      free fatty acids, and glycerol were significantly elevated compared to levels in
      chicks 1-4 d younger. Such changes did not occur in 1999. Blood levels of B were
      significantly correlated with brood size near the day of fledging, but not
      earlier, in both years of the study. It was possible to predict the day on which
      chicks would leave the nest, using their wing length when 12 d old. These results
      suggest that high blood levels of B associated with food restriction and sibling
      competition induce chicks to fledge, provided they have reached a critical size,
      and that the importance of fasting, sibling competition, and B may vary from year
      to year.

PMID- 11517451
TI  - The effect of the seasonal cycle on the splenic leukocyte functions in the turtle
      Mauremys caspica.
AB  - The reptile immune system is strikingly affected by seasonal variations, which
      induce changes in the structure of the lymphoid organs and in the function of the
      leukocytes. The aim of this work is to study several functions of splenic
      leukocytes from the turtle Mauremys caspica along its seasonal cycle. The
      functions assayed were adherence to substrate, mobility directed to a
      chemoattractant gradient (chemotaxis), lymphoproliferative response to mitogens,
      antibody-dependent cellular cytotoxicity, and natural killer-like cell-mediated
      cytotoxicity. Splenic leukocytes showed a positive response in all the assays,
      and this response was similar to that of mammals. In regard to the effect of the
      seasonal cycle, we have observed in winter a low adherence to substratum and high
      chemotaxis and cytotoxic activity, whereas in spring, only lymphoproliferation
      induced by mitogens showed high values except with lipopolysaccharide, which did
      not induce any seasonal variation in proliferation percentages. In summer, a high
      chemotaxis and cytotoxicity were observed, while in autumn, adherence to
      substratum was increased, but chemotaxis, cytotoxicity, and proliferation were
      clearly diminished. Our results demonstrate that splenic leukocyte functions are
      affected by the seasonal cycle, which induces a different pattern of response
      depending on the function studied.

PMID- 11517452
TI  - Effects of arginine on pancreatic hormones and hepatic metabolism in rainbow
      trout.
AB  - Arginine (Arg), injected intraperitoneally into rainbow trout (Oncorhynchus
      mykiss), increases plasma concentrations of glucagon, glucagon-like peptide-1
      (GLP-1), and insulin by three- to 10-fold. Resulting ratios of glucagon and GLP-1
      over insulin are unchanged in 20-d food-deprived fish (saline, 1.28 vs. Arg,
      0.93; not significant) while slightly increased in feeding trout (saline, 0.70
      vs. Arg, 0.92; P<0.05). In food-deprived juveniles, Arg injection leads to
      significant decreases in plasma fatty acids (saline, 1.65 mM L(-1) vs. Arg, 1.09
      mM L(-1); P<0.05) and increases in glycogen phosphorylase total activity (saline,
      3.7 units g(-1) vs. Arg, 4.6 units g(-1); P<0.05) and degree of phosphorylation
      (saline, 1.7 units g(-1) vs. Arg, 2.33 units g(-1); P<0.05). Plasma and liver
      glucose and liver enzymes (glucose-6-phosphate dehydrogenase, 6-phosphogluconate
      dehydrogenase, pyruvate kinase, phosphoenolpyruvate carboxykinase, lactate
      dehydrogenase, and malic enzyme) are unaffected. Otherwise, fish show the changes
      in plasma metabolites expected with food deprivation. Arg injection into feeding
      fish results in decreases in plasma fatty acids, liver glycogen, and glucose,
      while liver glucose 6-phosphate concentrations increase. Hepatocytes isolated
      from feeding fish injected with Arg 2 h previously show significantly lower rates
      of lactate oxidation than controls (85% of control), while rates of
      gluconeogenesis and hormonal responses to mammalian glucagon and GLP-1 remain
      unchanged. Rates of lactate oxidation and gluconeogenesis are significantly
      decreased by 5%-10% on treatment with porcine insulin. Complete
      immunoneutralization of insulin with rabbit antisalmon insulin serum decreases
      hepatic glucose 6-phosphate concentrations and abolishes the Arg-dependent
      effects on glycogen phosphorylase. It appears that short-term increases in
      pancreatic hormones cause only minor metabolic readjustments in the relatively
      short time frame covered in these experiments. Surprisingly, complete removal of
      insulin does not have immediate altering or detrimental effects on key
      metabolites and metabolic pathways, even if glucagon and GLP-1 concentrations are
      concurrently several-fold higher than usual. Our data clearly show the dual role
      of Arg in fish metabolism.

PMID- 11517453
TI  - Physiological control of warming and cooling during simulated shuttling and
      basking in lizards.
AB  - Differences in warming and cooling rates in basking lizards have long been
      thought to be brought about by adjustments in heart rate and blood flow. We
      examined the physiological control of warming and cooling in Iguana iguana,
      Sceloporus undulatus, and three species of Cordylus by measuring time constants,
      heart rate, and superficial capillary blood flow. Previously, techniques have not
      been available to measure time constants in shuttling animals. Using a
      combination of rapid measurements of temperature and blood flow and numerically
      intensive parameter-fitting methods, we measured dominant and subdominant time
      constants in lizards subjected to periods of both simulated basking and simulated
      shuttling. Cutaneous blood flow and heart rate were measured using laser Doppler
      flowmeters. Of the three, only the larger I. iguana measurably altered rates of
      warming and cooling during basking. During shuttling, none of the species
      effectively controlled warming and cooling. During both basking and shuttling,
      blood flow and heart rate tended to change in predicted directions. Superficial
      blood flow correlated with surface temperature while heart rate correlated more
      closely with core temperature. Changes in superficial blood flow and heart rate
      varied relatively independently in I. iguana. The techniques used here provide a
      better understanding of the ability of these species to control thermoregulation.

PMID- 11517454
TI  - Response of rainbow trout gill Na+-ATPpase to T(3) and NaCl administration.
AB  - The effect of the administration of commercial diets supplemented with 9 mg kg(
      1) 3,5,3'-triiodo-l-thyronine (T(3)) or 10% (w/w) NaCl was evaluated on the
      ouabain-insensitive Na+-ATPase activity in rainbow trout gill microsomes. The
      trial, carried out following the seasonal trend from March to mid-May, included a
      treatment phase in freshwater and a subsequent transfer to brackish water (22 per
      thousand salinity) where trout were not treated. pH dependence, apparent Km
      values for Mg(2+) and Na+, and Hill coefficients evaluated throughout the trial
      for Na+-ATPase were generally not affected by the treatments and habitat change.
      In comparison with the control group, in both treated groups, Na+-ATPase activity
      was lower during the freshwater phase and higher after brackish-water transfer.
      As compared with untreated trout, gill (Na++K+)-ATPase activity during the
      freshwater phase was stimulated by NaCl treatment and also by T(3) treatment
      after transfer to brackish water. The results indicate that NaCl and T(3)
      administration act differently on the two ATPase activities involved in Na+
      regulation and suggest a prevalent role of Na+-ATPase activity in hypoosmotic
      conditions.

PMID- 11517455
TI  - A biochemical study of fasting, subfeeding, and recovery processes in yellow
      legged gulls.
AB  - An investigation of the effects of fasting, subfeeding, and refeeding on plasma
      biochemistry was carried out on 22 captive yellow-legged gulls Larus cachinnans
      Pallas. These birds showed the same fasting endurance model described in other
      species, but with an important decrease in glucose plasma concentration and very
      great differences between individuals when reaching the deterioration limit,
      suggesting a moderate physiological adaptation to long periods of fasting. A
      different model was proposed in subfed gulls in relation to fasted gulls, based
      on lipid and protein use, which could be reflected by changes in nitrogen wastes
      and triglyceride levels in this experiment. Thus, the subfed gulls might use
      protein directly from the diet as an energy source, thereby reducing the use of
      fat stores. The gulls quickly recovered body mass during the refeeding period,
      but while some plasma substances quickly reached their initial values, others
      showed many changes before the end of the experiment, which could reflect a
      process of metabolic restabilization. These results contribute to a better
      knowledge of fasting, subfeeding, and refeeding processes in birds and can be
      added to a recent study about fasting in gulls.

PMID- 11517456
TI  - Effects of changing ambient temperature on metabolic, heart, and ventilation
      rates during steady state hibernation in golden-mantled ground squirrels
      (Spermophilus lateralis).
AB  - To determine whether metabolic rate is suppressed in a temperature-independent
      fashion in the golden-mantled ground squirrel during steady state hibernation, we
      measured body temperature and metabolic rate in ground squirrels during
      hibernation at different T(a)'s. In addition, we attempted to determine whether
      heart rate, ventilation rate, and breathing patterns changed as a function of
      body temperature or metabolic rate. We found that metabolic rate changed with
      T(a) as it was raised from 5 degrees to 14 degrees C, which supports the theory
      that different species sustain falls in metabolic rate during hibernation in
      different ways. Heart rate and breathing pattern also changed with changing T(a),
      while breathing frequency did not. That the total breathing frequency did not
      correlate closely with oxygen consumption or body temperature, while the
      breathing pattern did, raises important questions regarding the mechanisms
      controlling ventilation during hibernation.

PMID- 11517457
TI  - Rubidium uptake is increased in shore crabs, Carcinus maenas, acclimated to
      dilute seawater.
AB  - In dilute seawater, Carcinus maenas hyperosmoregulates by actively absorbing Na,
      K, and Cl. Here we characterize K uptake using a novel technique. Rb was used as
      a tracer for K transport, and hemolymph Rb levels were measured using cation
      chromatography. Hemolymph Rb was detectable at 0.1 mmol L(-1), which enabled
      determination of initial rate of Rb uptake. Crabs maintained for 3 wk in dilute
      artificial seawater (35% ASW crabs) maintained Na and K above the level of the
      external media and had elevated Na-K-ATPase activity in the posterior gills. In
      assay conditions matched to 100% ASW, Rb uptake was the same in 35% ASW crabs
      (0.45+/-0.04 micromol g(-1) h(-1)) and in crabs acclimated to normal seawater
      (100% ASW crabs, 0.49+/-0.05 micromol g(-1) h(-1)). In assay conditions matched
      to 35% ASW, Rb uptake was greater in 35% ASW crabs (0.28+/-0.03 micromol g(-1) h(
      1)) compared with 100% ASW crabs (0.10+/-0.04 micromol g(-1) h(-1)). Low external
      [Rb] or reduced salinity were found to contribute independently to the difference
      between 100% ASW and 35% ASW crabs. Thus, whole-body Rb uptake in crabs can be
      measured by cation chromatography, and Rb uptake is greater in 35% ASW crabs than
      in 100% ASW crabs.

PMID- 11517458
TI  - Exposure to ultraviolet radiation (290-400 nm) causes oxidative stress, DNA
      damage, and expression of p53/p73 in laboratory experiments on embryos of the
      spotted salamander, Ambystoma maculatum.
AB  - Developing embryos of the spotted salamander, Ambystoma maculatum, exposed to
      ultraviolet radiation (UVR; 290-400 nm) in the laboratory show a significant
      sensitivity to UVB (290-320 nm) radiation. Embryos in laboratory experiments
      exhibited significant DNA damage during exposures to UVR despite a significant
      increase in the production of the protective pigment melanin in response to UVR
      exposure. DNA damage occurs as a result of both the direct effects of exposure to
      UVR, and the indirect effects are mediated by the production of reduced oxygen
      intermediates. The production of reactive oxygen species initiates the expression
      of p53/p73 that leads to either DNA repair or apoptosis. When similar experiments
      are conducted on salamander embryos exposed to solar UVR in vernal pools, the
      embryos show significantly less sensitivity and higher survivorship. The
      differences between laboratory and field experiments are a result of the
      attenuation of UVR caused by the accumulation of dissolved organic carbon within
      the pools of these wooded areas. These findings suggest that northeastern
      populations of spotted salamanders are sensitive to UVR but are not significantly
      affected by present-day irradiances of UVR in the field. These results do suggest
      that continued decreases in stratospheric ozone over temperate latitudes have the
      potential to affect spotted salamanders in their natural habitats.

PMID- 11517459
TI  - Effects of dietary fibre on digesta passage, nutrient digestibility, and
      gastrointestinal tract morphology in the granivorous Mongolian gerbil (Meriones
      unguiculatus).
AB  - To investigate digestive tract performance in Mongolian gerbils (Meriones
      unguiculatus), food intake and digestibility, digesta passage rate, and
      gastrointestinal tract morphology were measured in captive animals fed low- or
      high-fibre diets. We used two markers (Co-ethylene diamine tetra-acetic acid for
      solutes and Cr-mordanted cell walls for particles) to measure differential
      passage rates of digesta fractions in order to test for the presence of a colonic
      separation mechanism (CSM). Although dry-matter intakes on the high-fibre diet
      did not differ from those on the low-fibre diet, digestibilities of dry matter,
      neutral-detergent fibre, acid-detergent fibre, crude protein, and crude fat were
      all significantly lower on the high-fibre diet. Gross energy intake on the high
      fibre diet also did not differ from that on the low-fibre diet, but energy lost
      in faeces was much higher than on the low-fibre diet; thus, energy digestibility
      and digestible energy intake were significantly lower on the high-fibre diet. The
      lengths and dry-tissue masses of all segments of the gastrointestinal tract
      tended to enlarge in response to increased dietary fibre, but only the total
      tract contents, contents of the small intestine, and length and dry-tissue mass
      of the caecum increased significantly. The mean retention time (MRT) of the
      particle marker was significantly greater than that of the solute marker on the
      low-fibre but not the high-fibre diet; the solute/particle differential retention
      ratio was 0.62 on the low-fibre diet and 0.90 on the high-fibre diet. Thus, there
      was no evidence for selective retention of the solute marker on either diet. The
      MRT of the particle marker was significantly lower on the high-fibre diet and in
      the same direction as the MRT of the solute marker. These results suggest that
      the granivorous Mongolian gerbil has no CSM but can adjust its digestive tract
      capacity to accommodate greater quantities of low-quality food.

PMID- 11517460
TI  - Blood and extracellular fluid volume in whole body and tissues of the Pacific
      hagfish, Eptatretus stouti.
AB  - Whole-body and 20 individual-tissue (51)Cr-RBC (red cell space; RCS) and (99)Tc
      diethylenetriaminepentaacetic acid (extracellular space; ECS) spaces were
      measured in seven unanesthetized Pacific hagfish (Eptatretus stouti). Volume
      indicators were administered via a dorsal aortic cannula implanted the previous
      day. Blood samples were collected at 6, 12, 18, and 24 h after injection. Tissues
      were removed at 24 h and radioactivity was measured; tissue water content
      (percent of wet weight) was determined by desiccation at 95 degrees C for 48 h.
      Mixing rates of both indicators were identical and were essentially complete by
      12 h, indicating that blood convection is the rate-limiting process. At 24 h, the
      whole-body RCS was 19.3+/-2.1 mL kg(-1) body weight, and the ECS was 338.5+/-15.2
      mL kg(-1) body weight. Blood volume estimated from the 24-h RCS and the mean
      central hematocrit (14%) was 137.9 mL kg(-1) body weight. Liver RCS (118.6+/-30.5
      microL g(-1) tissue weight) was twice that of any other tissue and was also the
      most variable, ranging from 59 to 263 microL g(-1), whereas liver ECS (406.0+/
      34.3 microL g(-1)) was in the range of other tissues, and water content (66.9%+/
      3.5%) was low. Gill RCS (55.9+/-5.7 microL g(-1)), ECS (415.3+/-37.7 microL g(
      1)), and percent water (83.1%+/-0.8%) were higher than most other tissues. RCS,
      ECS, and percent water were consistently lowest in ovum (1.1+/-0.02 microL g(-1),
      111.1+/-4.3 microL g(-1), 51.3%+/-3.5%, respectively). Tongue, notocord, and
      myotome had generally lower RCS (2.1+/-0.4, 2.2+/-0.5, 7.1+/-0.1 microL g(-1),
      respectively) and ECS (121.2+/-7.0, 246.3+/-17.4, 185.3+/-16.7 microL g(-1),
      respectively), although their water content was in the midrange (74.7+/-0.5,
      81.2+/-1.6, 74.4%+/-0.6%, respectively). Skin had a low RCS (6.8+/-1.1) and
      midrange ECS (387.5+/-28.0) but very low water content (61.2%+/-2.1%). These
      findings confirm that hagfish blood volume is at least twice as large as other
      fish, whereas our estimate of extracellular fluid volume is larger than
      previously reported and more in line with the predicted interstitial volume. RCS,
      ECS, and water content vary, often independently, between tissues, which may
      perhaps be indicative of specific tissue needs or functions. A distinct spleen is
      lacking in hagfish, and the liver appears to serve this function by sequestering
      red cells. To our knowledge, this is the first report of tissue ECS in
      Myxiniformes.

PMID- 11517461
TI  - Scaling of CO2 production in the timber rattlesnake (Crotalus horridus), with
      comments on cost of growth in neonates and comparative patterns.
AB  - To understand the bioenergetic fluxes of free-ranging timber rattlesnakes
      (Crotalus horridus) better, we measured CO(2) production rate of 83 snakes in
      response to body mass, body temperature, time of day, sex, and geographic
      locality (northwest Arkansas and coastal Virginia). Effects of body mass,
      temperature, time of day, and the temperature-by-time interaction were remarkably
      similar to effects reported for other rattlesnakes. We noted that C. horridus has
      relatively high, but precedented, Q(10) (3.71-4.78); however, the adaptive
      significance of this observation, if any, remains obscure. Once the confounding
      effect of body mass was statistically adjusted, C. horridus exhibited no sex
      specific effects; however, there was a significant locality-by-time effect, which
      is of equivocal biological significance. In contrast to the findings of a recent
      review on cost of growth in neonatal reptiles, C. horridus neonates exhibited
      metabolic rates that were from 200% to 400% greater than expectations from the
      mass scaling of yearlings and older animals. We interpreted this as evidence for
      a cost of synthesis in growing neonates. We report regression equations for the
      estimation of resting CO(2) production rate in C. horridus as a function of body
      mass, body temperature, and time of day. Our data contribute to a growing,
      comparative database documenting rattlesnakes as low-energy specialists.

PMID- 11517462
TI  - Developmental changes in digestive physiology of nestling house sparrows, Passer
      domesticus.
AB  - Six decades of studies have speculated that digestive capacity might limit avian
      growth rate or that developmental changes in the gut might determine
      developmental changes in digestive efficiency. However, there are no studies on
      digestive enzymes during avian development, except for studies on mainly domestic
      birds that exhibit the precocial mode of development. We studied alimentary organ
      masses, intestinal enzyme activities (sucrase, maltase, isomaltase,
      aminopeptidase-N), and pancreatic enzyme activities (amylase, trypsin,
      chymotrypsin) during development of a wild passerine bird exhibiting the
      altricial mode of development. Wild nestling house sparrows were studied
      immediately after removal from the nest (days 0, 3, 6 of age; day 0=hatch),
      whereas captives were raised in the laboratory beginning day 3 on a formulated
      casein/starch-based diet until fledging age (after day 12). Digestive
      biochemistry was dynamic. Tissue-specific activities of some digestive enzymes
      continued to increase through fledging, by >10 times in some cases (e.g., sucrase
      and maltase in midintestine). Total pancreatic amylase activity increased 100
      times between hatch and day 12 through a combination of increases in tissue
      specific activity and pancreas mass. House sparrows differ from poultry, in whom
      after about 2 wk of age the specific activity of intestinal and pancreatic
      digestive enzymes is generally constant or declines during development. The data
      on intestinal and pancreatic enzymes help explain why digestive efficiency of
      nestling house sparrows improves with age, and the data seem consistent with the
      idea that digestive capacity might limit feeding rate and hence growth rate.

PMID- 11517463
TI  - Evolution of body-wall musculature in the Platyhelminthes (Acoelomorpha,
      Catenulida, Rhabditophora).
AB  - In an effort to understand the phylogeny of the Platyhelminthes, the patterns of
      body-wall musculature of flatworms were studied using fluorescence microscopy and
      Alexa-488-labeled phalloidin. Species of the Catenulida have a simple orthogonal
      gridwork of longitudinal and circular muscles. Members of the Rhabditophora have
      the same gridwork of musculature, but also have diagonal muscles over their
      entire body. Although a few species of Acoelomorpha possessed a simple orthogonal
      grid of musculature, most species typically have distinctly different patterns of
      dorsal and ventral body-wall musculature that include sets of longitudinal,
      circular, U-shaped, and several kinds of diagonal muscles. Several distinct
      patterns of musculature were identified, including 8 patterns in 11 families of
      acoels. These patterns have proven to be useful in clarifying the phylogeny of
      the Acoelomorpha, particularly with regard to the higher acoels. Patterns of
      musculature as well as other morphological characters are used here for revisions
      of acoel systematics, including the return of Eumecynostomum sanguineum
      (Mecynostomidae) to the genus Aphanostoma (Convolutidae), the revision of the
      family Childiidae, and the formation of a new family, Actinoposthiidae.

PMID- 11517464
TI  - Functional morphology of the pectoral fins in bamboo sharks, Chiloscyllium
      plagiosum: benthic vs. pelagic station-holding.
AB  - Bamboo sharks (Chiloscyllium plagiosum) are primarily benthic and use their
      relatively flexible pectoral and pelvic fins to rest on and move about the
      substrate. We examined the morphology of the pectoral fins and investigated their
      locomotory function to determine if pectoral fin function during both benthic
      station-holding and pelagic swimming differs from fin function described
      previously in leopard sharks, Triakis semifasciata. We used three-dimensional
      kinematics and digital particle image velocimetry (DPIV) to quantify pectoral fin
      function in five white-spotted bamboo sharks, C. plagiosum, during four
      behaviors: holding station on the substrate, steady horizontal swimming, and
      rising and sinking during swimming. During benthic station-holding in current
      flow, bamboo sharks decrease body angle and adjust pectoral fin angle to shed a
      clockwise fluid vortex. This vortex generates negative lift more than eight times
      that produced during open water vertical maneuvering and also results in an
      upstream flow that pushes against the posterior surface of the pectoral fin to
      oppose drag. In contrast, there is no evidence of significant lift force in the
      wake of the pectoral fin during steady horizontal swimming. The pectoral fin is
      held concave downward and at a negative dihedral angle during steady horizontal
      swimming, promoting maneuverability rather than stability, although this negative
      dihedral angle is much less than that observed previously in sturgeon and leopard
      sharks. During sinking, the pectoral fins are held concave upward and shed a
      clockwise vortex with a negative lift force, while in rising the pectoral fin is
      held concave downward and sheds a counterclockwise vortex with a positive lift
      force. Bamboo sharks appear to sacrifice maneuverability for stability when
      locomoting in the water column and use their relatively flexible fins to generate
      strong negative lift forces when holding position on the substrate and to enhance
      stability when swimming in the water column.

PMID- 11517465
TI  - Patterns of carpal development among anuran amphibians.
AB  - The unity and diversity of developmental processes in the vertebrate limb have
      singular importance in the interpretation of evolutionary hypotheses of tetrapod
      diversification. In anurans, the intraordinal diversity of forelimbs seems to be
      related to the fusion of distal carpals, whereas proximal carpals are invariable.
      However, there are different ontogenetic pathways involved in the differentiation
      of proximal carpals. This study presents a comparative analysis of early
      developmental features in one archeobatrachian and 23 neobatrachian species
      representing five families and explores the variability in the differentiation of
      carpal cartilages. We found new evidence supporting the presence of an embryonic
      intermedium that incorporates with the ulnare. Difference between the pipid
      Xenopus and the neobatrachians is interpreted as a change in the rate of
      differentiation of Distal Carpal 5 that does not affect the developmental pattern
      of digits. The developmental variability exhibited by the intermedium, radiale,
      and Element Y is combined in patterns that converge on the same adult carpal
      morphology among neobatrachians; these patterns appear to contain potentially
      useful phylogenetic information.

PMID- 11517466
TI  - Transverse masticatory movements, occlusal orientation, and symphyseal fusion in
      selenodont artiodactyls.
AB  - Based on extensive experimental work on primates, two masticatory loading regimes
      have emerged as the likely determinants of mandibular symphyseal fusion
      dorsoventral shear and lateral transverse bending (wishboning) (Ravosa and
      Hylander, 1994; Hylander et al., 1998, 2000). Recently, however, it has been
      argued that, rather than functioning to strengthen the symphysis during
      mastication, fusion serves to stiffen the symphyseal joint so as to facilitate
      increased transverse jaw movements during occlusion (Lieberman and Crompton,
      2000). As part of this transverse stiffness model, it has been suggested that
      taxa with fused symphyses should also exhibit more horizontally oriented occlusal
      wear facets. Using a series of univariate and bivariate analyses, we test
      predictions of these three models in a sample of 44 species of selenodont
      artiodactyls. Consistent with the wishboning and transverse stiffness models,
      taxa with fused symphyses (camelids) have more horizontally oriented M(2) and
      M(2) occlusal wear facets, anteroposteriorly (AP) elongate symphyses, and
      relatively wider corpora. Contrary to the dorsoventral shear model, camelids do
      not have relatively deeper corpora (due to greater parasagittal bending). While
      taxa with ossified symphyses have relatively larger symphysis cross-sectional
      areas, this appears to be the byproduct of an increase in AP symphysis length due
      to greater lateral transverse bending of the mandible. Theoretical consideration
      of the biomechanics of mastication further suggests that strength, not stiffness,
      is the critical factor in determining symphyseal ossification. Thus, like
      anthropoid primates, fusion in selenodont artiodactyls appears to function in
      resisting increased wishboning stresses arising from an emphasis on transverse
      occlusal/mandibular movements and loads.

PMID- 11517467
TI  - Embryogenesis of the dipluran Lepidocampa weberi Oudemans (hexapoda: diplura,
      campodeidae): formation of dorsal organ and related phenomena.
AB  - The developmental changes of embryonic membranes of a dipluran Lepidocampa
      weberi, with special reference to dorsal organ formation, are described in detail
      by light, scanning, and transmission electron microscopies. Newly differentiated
      germ band and serosa secrete the blastodermic cuticle at the entire egg surface
      beneath the chorion. Soon after, the serosal cells start to move dorsad. All the
      serosal cells finally concentrate at the dorsal side of the egg and form the
      dorsal organ. During their concentration, the serosal cells attenuate their
      cytoplasm to form filaments. The extensive area from which the serosa has receded
      is occupied by a second embryonic membrane, the amnion, which originates from the
      embryonic margin. The embryo and newly emerged amnion then secrete three fine
      cuticular layers, "cuticular lamellae I, II, and III," above which the filaments
      of the (developing) dorsal organ are situated. With the progression of definitive
      dorsal closure, the amnion reduces its extension, the dorsal organ is
      incorporated into the body cavity of the embryo, and the amnion and dorsal organ
      finally degenerate. The dorsal organ of diplurans is formed by the concentration
      of whole serosal cells, while that of collembolans is formed by the direct
      differentiation of a part of serosal cells. However, the dorsal organs of
      diplurans and collembolans closely resemble each other in major aspects,
      including that of ultrastructural features, and there is no doubt regarding their
      homology. The amnion, which has been regarded as being a characteristic of
      Ectognatha, also develops in the Diplura. This might suggest a closer affinity
      between the Diplura and Ectognatha than previously believed.

PMID- 11517468
TI  - The development of the skull in Acrochordus granulatus (Schneider) (Reptilia:
      Serpentes), with special consideration of the otico-occipital complex.
AB  - The skull of Acrochordus has been characterized by the absence of a crista
      circumfenestralis (a synapomorphy shared by all snakes), and by the absence of a
      recessus scalae tympani that in other squamates forms by subdivision of the
      embryonic metotic fissure. These traits have variably been identified as either
      plesiomorphic or paedomorphic. The study of the development of the osteocranium
      in a series of cleared and stained embryos of Acrochordus shows a close
      correspondence to the development of the skull in other snakes. The exception is
      the formation of the postorbital from two ossification centers. The significance
      of this observation, which might suggest the embryonic fusion of a postfrontal
      with a postorbital, remains enigmatic, as it is based on one side only of the
      skull of a single specimen. By contrast, a rudimentary and modified crista
      circumfenestralis can be identified in the skull of Acrochordus. Furthermore,
      absence of a recessus scalae tympani is not due to an undivided fissura metotica,
      but results from the obliteration of the anterior part of the metotic fissure
      instead. With respect to this character, Acrochordus is neither plesiomorphic,
      nor paedomorphic, but autapomorphic. This interpretation of the skull of
      Acrochordus is compatible with the sister-group relationships this genus shares
      with colubroid snakes.

PMID- 11517469
TI  - [Thalamic hypertensive hemorrhage].
AB  - We performed statistic analysis of the results of both conservative and surgical
      (by means of laying on the external ventricle drain--EVD) treatment of 23
      patients with thalamic (medial) hypertensive hemorrhage (THH) admitted to the
      hospital in the first two days of the stroke's beginning. We also investigated
      clinical tomographic factors which had influence either on the choice of the
      treatment or on the prognosis of the disease. The frequency of the lethal cases
      in EVD-group (6 observations) was about twice lower than in analogous group of
      patients treated conservatively (17 cases). In conservative treatment
      prognostically unfavourable factors in acute period of the stroke were the
      following: the awakening level lower than 10 points according to Glasgow Scale,
      development of acute obstructive hydrocephalus, dislocation of brain stem, break
      of blood into cerebral ventricles (of II-IV degree), the volume of hemorrhage
      more than 10 ml for thalamic and thalamo-capsular location and more than 5 ml for
      thalamo-mesencephalic location. Monitoring of intracranial pressure in patients
      with THH which had factors mentioned above revealed the development of steadfast
      intracranial hypertension by days 5-7 maximally. The laying on EVD was indicated
      in patients with unfavourable signs of THH by means of ventricle drainage. The
      controlled decrease of intracranial pressure increased the level of awakening,
      meanwhile it decreased the degree of hydrochephalus and dislocation of brain
      stem.

PMID- 11517470
TI  - [Role of autonomic dysfunction syndrome in the etiology of pre-stroke forms of
      cerebrovascular pathology in women of young age].
AB  - 30 women aged 30-45 years with the diagnosis "initial manifestations of
      insufficiency of cerebral circulation" were examined. These disorders were
      observed on the background of the syndrome of autonomic dysfunction. Correlative
      analysis was performed by means of methods which permitted quantitative
      estimations on the basis of investigation of the severity of the syndrome,
      peculiarities of the patients' mental state and cerebral hemodynamics. Pronounced
      correlation was found between hemodynamic indices and the degree of anxieties.
      Anxiety plays an inducing role in the development of either autonomic dysfunction
      or the main vascular disorders. The syndrome of autonomic disfunction was
      considered as the realising factor.

PMID- 11517471
TI  - [Premorbid states in borderline mental disorders].
AB  - Clinico-epidemiological and repeated catamnestic investigations were performed in
      juveniles and individuals of young age (14-26 year old) in relation to
      prevalence, structure and dynamics of premorbid neurological disorders and
      typical personality reactions. Observations were carried out every 4 years.
      Results of analysis testified the development of borderline mental disorders in
      one third of teenagers with preneurotic and pronounced characterological
      reactions. That permitted to consider these deviations as "risk factors" of the
      appearance of both neuroses and psychopathies.

PMID- 11517472
TI  - [Effectiveness of semax in acute period of hemispheric ischemic stroke (a
      clinical and electrophysiological study)].
AB  - Efficiency of Semax (synthetic derivative of ACTH-4-10) was studied in 30
      patients in acute period of hemispherical ischemic stroke. Control group
      consisted of 80 patients with the strokes analogous in severity and location of
      the damages and which were treated by conventional therapy. Different clinical
      rating scales were used for both objectivization of the severity of the patients'
      state and estimation of the degree of neurological defect. The control of Semax
      influence on the functional state of the brain included monitoring of EEG with
      mapping, repeated analysis of somatosensory evoked potentials and their mapping.
      It was established that including of Semax in combined intensive therapy of acute
      ischemic stroke had some influence on the rate of restoration of the damaged
      neurological functions in terms of increasing the regress of general cerebral and
      focal, especially motor disorders. The most effective daily doses were 12 mg for
      patients with strokes of moderate severity and 18 mg for patients with severe
      strokes (treatment course--5 and 10 days).

PMID- 11517473
TI  - [State of the hemostasis system and pathogenetic therapy of circulatory
      encephalopathy].

PMID- 11517474
TI  - [Use of cerebrolysin in the treatment of prolonged extrapyramidal complications
      of neuroleptic therapy].
AB  - Open study was performed concerning the efficiency of cerebrolysin in treatment
      of tardive dyskinesia and parkinsonism. 30 patients of middle (18-41 years) and
      old (60-82 years) age were examined by means of Extrapyramidal Symptom Rating
      Scale and Abnormal Involuntary Movement Scale. Cerebrolysin was administered
      intravenously by drops every other day in a dose of 5-10 ml during 28 days.
      Significant decrease of the severity of extrapyramidal symptoms (according to the
      Scales used) was observed by the end of the course of therapy. The number of the
      responders was 46.6%, of the partial responders--26.6%. Efficiency of
      cerebrolysin was the same both in the groups of patients with drug-induced
      parkinsonism (number of the responders--54.5%) and in patients with tardive
      dyskinesia (the responders' number--60%). The efficiency of cerebrolysin was
      lower in patients with combination of symptoms of parkinsonism and tardive
      dyskinesia as well as in ones with pronounced negative schizophrenic disorders in
      clinical picture. Efficacy of cerebrolysin was also the same in patients of both
      middle and old age. Its efficiency was equally high independently on the duration
      of extrapyramidal disorders' existence.

PMID- 11517475
TI  - [New findings concerning pathogenesis of disorders of cerebral circulation].
AB  - The data about the role of blood flow in atherosclerosis development were
      examined. The aim of the study was determination of hydrodynamic blood resistance
      and Toms effect in patients with ischemic disorders of cerebral circulation in
      different periods of the disease. 45 patients with atherosclerotic damages of
      major arteries of head were observed. Such damages were combined with arterial
      hypertension in 32 individuals. The value of hematocrit, asymptotic viscosity,
      hydrodynamic resistance and Toms' effect were determined in blood as well as
      levels of cholesterol, beta-lipoproteins and platelets. The presence of Toms'
      effect was found in blood samples of both patients and controls. There was a
      significant increase of hydrodynamic blood resistance in all the patients as
      compared to control group. The patients with ischemic disorders of cerebral
      circulation were compensated by their own blood factor in less degree in acutest
      and acute periods than later. Low values of Toms' effect in separate patients
      were prognostic sings for good restoration of neurologic functions; higher values
      were observed in patients with arterial hypertension. The conclusion was made
      that hemodynamic properties of blood flow may be considered as predictors of the
      severity of the course of cerebral circulation disorders.

PMID- 11517476
TI  - [Magnetic resonance angiography in patients with ischemic vertebrobasilar
      stroke].
AB  - The analysis of sensitivity and specificity of magnetic resonance angiography
      (MRA) was performed in investigation of vertebral and basilar arteries in 29
      patients with acute vertebrobasilar insufficiency. MRA data were compared with
      the results of ultrasonic dopplerography of the same vessels including duplex
      scanning and figures subtractive angiography. Highly satisfactory efficiency of
      MRA was demonstrated. Peculiarities of both visualization of the intact vessels
      and of different variations of their obstruction as well as indications for
      performing diagnostic MRA are considered.

PMID- 11517477
TI  - [Reactivity of cerebral vessels in occlusive lesions of carotid arteries].
AB  - Cerebrovascular CO2 reactivity was examined in 62 patients with occlusive damages
      of carotid arteries (42 with atherosclerosis, 20 with non-specific aorto
      arteritis). Control group consisted of 20 volunteers aged 30-60 years without any
      signs of cerebrovascular pathology. Increase of blood flow in the middle brain
      artery during 5-minutes of 5% CO2 inhalation was the main quantitative index
      which determined autoregulative reaction of cerebral vessels (ARCV). One of the
      main factors which determined the values of ARCV occurred to be the degree of the
      damage of carotid arteries. ARCV was not significantly changed in stenosis (up to
      80%) as compared to controls. Meanwhile its value was equal to 12 + 4.1 and 13 +
      4.2 c/s in stenosis (more than 80%). In other words ARCV permitted to determine
      hemodynamic significance of the damages of carotid arteries and of
      brachiocephalic trunk. Cerebrovascular CO2 reactivity permitted to determine
      either hemodynamic significance of the damages of carotid arteries or collateral
      reserve capacity of blood vessels. The was quite important for more precise
      determination of both medical policy and indication of surgical treatment in
      occlusive damages of carotid arteries.

PMID- 11517478
TI  - [Autoantibodies to NMDA-type glutamate receptors in the blood of patients with
      acute ischemic and hemorrhagic stroke].
AB  - The characteristics of accumulation of autoantibodies (aAbs) on NMDA-type
      glutamate receptors were studied in blood of patients at different stages (1-4
      days, 5-7 days, 8-14 days, up to 28 days) of acute period of ischemic or
      hemorrhagic stroke. The stability of low values (1.29 +/- 0.31 ng/ml) of the
      titer of aAbs to NMDA-receptors was revealed in patients with acute cerebral
      hemorrhage. Two types of titer of Abs to NMDA-receptors were revealed in case
      with cerebral ischemia. The undulating nature of Abs titer changes was revealed
      in acute ischemic strokes caused by hypertension and cerebral atherosclerosis
      (from 2.23 +/- 0.53 ng/ml on the 1-st day with increase up to 3.23 +/- 0.90 ng/ml
      and up to the 3-4 day), following fluctuations with less pronounced increase on 7
      8th day were found out. High titer of aAbs to NMDA-receptors (up to 10.0 ng/ml)
      were observed on 3-4th day in cases of acute ischemic strokes on the background
      of chronic alcohol encephalopathy caused by intoxication or dysmetabolism with
      their retention up to 10-14th day.

PMID- 11517479
TI  - [Antibodies to phospholipids and ischemic disorders of cerebral circulation in
      young age].
AB  - Antibodies to phospholipids (APL) were studied in 97 patients which had ischemic
      stroke in young age (up to 46 years). These antibodies (Abs) were found in 25
      patients (26%): Abs to cardiolipin--in 15 patients (60%), Abs to lupoid
      anticoagulant in 18 from 24 patients (75%), Abs to phosphatidylethanolamine--in 4
      from 13 patients (31%). Disorders of cerebral circulation (DCC) usually began at
      the age of 14-45 years and were characterized by ischemic strokes and by
      transitory DCC. There was no correlation between the occlusion of extracranial
      arteries and their hemodynamic significant stenosis. There was occlusion of
      intracranial arteries in 7 from 12 patients (58%). Other risk factors of the
      stroke development were also found in 19 patients (76%) together with Abs to
      phopholipids. Other manifestations of antiphospholipid syndrome (APLS) were
      observed in 68% of the patients: miscarriage of pregnancy (63%), thrombosis of
      peripheric veins (16%), thrombocytopenia (32%), ischemic heart disease (28%).
      Comparison of APL+ and APL- patients revealed that transitory DCC, occlusion of
      intracranial arteries, intact extracranial arteries, widening or condensation of
      the cardial valves on echo-ECG, abortions, increase of ESR were significantly
      more frequently observed in the former group. For confirmation of APLS diagnosis
      it was necessary to study simultaneously Abs to cardiolipin and lupoid
      anticoagulant. Prophylaxis of repeated DCC in APLS included administration of
      both aspirin and anticoagulants of indirect action.

PMID- 11517480
TI  - [The Dolittle syndrome].

PMID- 11517481
TI  - [Transcranial magnetic stimulation in psychiatry].

PMID- 11517482
TI  - [Clinical and morphological essence of initial manifestations of insufficiency of
      cerebral blood supply].

PMID- 11517483
TI  - [Suicides in the Russian Federation as a sociopsychiatric problem].
AB  - The analysis of suicide situation in Russia in 1989-1993 is presented.
      Unfavourable trends have been identified: growth of suicides prevalence and
      younger age of their committing. The differentiation of Russian regions according
      to suicide rates is also presented. While suicide prevalence was 37.9 per 100,000
      among general Russian population it was more than twice as high among mentally
      ill, in outpatient clinic, that is 78.2. 1738 mentally ill suicide cases have
      been considered. Most of these suicides have been committed by patients at the
      age of 30-59 years. Schizophrenic patients prevailed--55.6% of cases. It was
      found that unlike general population age-sex structure of the population
      considered was more stable and wasn't changed under the influence of social
      factors. The changes in the nosological structure of the above population
      depended on the changes of the psychiatric registration procedure.

PMID- 11517484
TI  - [Glutamate receptors in the central nervous system].

PMID- 11517485
TI  - [Pituitary tumor from molecular-biological aspects].

PMID- 11517487
TI  - [The role of transplanted astrocytes for the regeneration of CNS axons].
AB  - Long tract axons in the mammalian CNS do not normally regenerate for appreciable
      distance after they transected. But we reported transplantation of Schwann
      cells(SCs) or olfactory ensheathing cells induced regeneration of transected rat
      dorsal column (DC) axons and improved the conduction. Scar formation(gliosis),
      for which astrocytes(ACs) play an important role, may be one of strong and
      physical barriers for the regeneration of CNS axon. Oligodendrocyte and myelin
      associated protein or products also inhibit the regeneration of the axons, as
      chemical barriers. To investigate how effective the promotion or the reduction of
      scar or myelin formation may be for axonal regeneration, we transplanted AC into
      transected DCs, or radiated(X-ray) the DCs, and compared to normal DCs or
      regenerated DCs following by SC transplantation. DCs of adult rats were
      transected at Th 11 and transplanted with SCs(6 x 10(4)) of adult rats or ACs(6 x
      10(4)) of neonatal rats. Five to six weeks later, the spinal cords were removed
      and pinned in a recording chamber, and compound action potentials (CAPs) along
      the DC through the transected lesion were recorded, to investigate conduction
      properties(conduction velocity and response after high frequency stimulations).
      Following transplantation of SCs or ACs, histological examination revealed
      regenerated axons with SC-like patterns of remyelination in transected DCs. X-ray
      irradiation did not enhance the regeneration of DC axons. SC transplantation
      improved the conduction properties of transected DCs and increased the number of
      regenerated axons, compared to transected DCs without cell transplantation. AC
      transplantation resulted in improvement of the conduction properties, but the
      number of regenerated axons was similar to that of transected DCs without the
      transplantation. X-ray irradiation (40 Gy) three days before DC transection and
      AC transplantation prevented the electrophysiological continuity of axons through
      the transected lesion. This evidence revealed that AC transplantation secondarily
      enhanced the regeneration of axons, probably endogeneous SCs of dorsal roots
      migrated into the transected lesion and enhanced the axonal regeneration.

PMID- 11517486
TI  - [Effect of sumatriptan on cerebral blood flow during migraine headache:
      measurement by sequential SPECT used 99mTc-ECD background subtraction method].
AB  - The present study was designed to examine the effect of sumatriptan on regional
      cerebral blood flow (CBF) during migraine headache. Nine cases were examined by
      99mTc-ECD background subtraction method for the absolute value measurement of
      regional CBF before and after sumatriptan injection. rCBF except for occipital
      and perioccipital lobes, were increased 10-20% during migraine headache and
      significant decreases were observed by sumatriptan injection. Two cases of nine
      had transiently increased systemic blood pressure and cardiac pulse rate,
      however, all cases improved migraine headache after injection of sumatriptan.

PMID- 11517488
TI  - [The effect of C 1 esterase inhibitor on ischemia: reperfusion injury in the rat
      brain].
AB  - BACKGROUND: Despite the current interest in thrombolytic therapy for acute
      stroke, ischemia-reperfusion injury remains a potentially hazardous complication.
      The complement system is thought to play a major role in initiating some of the
      inflammatory events occurring in the reperfusion injury. This study was conducted
      to explore the effect of C 1 esterase inhibitor (C 1 INH) on the reperfusion
      injury in rat middle cerebral artery (MCA) occlusion-reperfusion model. METHODS:
      Twenty-nine male Wistar rats were used. Intraluminal MCA occlusion was performed
      for 60 minutes. Just before the reperfusion, C 1 INH(50 IU/kg, C 1 INH group, n =
      15) or saline (control group, n = 14) was administrated. Forty-eight hours after
      the reperfusion, infarct volume and myeloperoxidase(MPO) activity of the brain
      were evaluated. RESULT: Infarct volume and MPO activity were significantly
      smaller in the C 1 INH group(86.5 +/- 76.8 mm3, 0.38 +/- 0.30 U/g) than in
      control group(179 +/- 92.8 mm3, 1.37 +/- 0.46 U/g) (p < 0.01). CONCLUSION: The
      results of this study provided the first evidence that C 1 INH reduced
      polymorphonuclear leukocytes(PMN) accumulation and reperfusion damage in the
      brain.

PMID- 11517489
TI  - [A case of SLE presenting the features of antiphospholipid antibody syndrome
      during a treatment for complicated cryptococcal meningitis].
AB  - A 39-year-old woman had developed systemic lupus erythematosus(SLE) at the age of
      29. She had a long history of immunosuppressant therapies such as corticosteroid.
      On admission, she presented a headache due to the cryptococcal meningitis which
      was confirmed by lumbar puncture. Combined medications of amphotericin B and
      fluconazole were not effective, and combined amphotericin B and flucytosine were
      replaced. Prednisolone and methotrexate had been tapered gradually. Fifty days
      after the initial treatment for meningitis Cryptococcal neoformans was not
      observed in the cerebrospinal fluid. Sixty days after the treatment,
      thrombocytopenia was observed with positive lupus anticoagulant and
      anticardiolipin antibody. Following which, thrombophlebitis occurred in the left
      brachium. We suggest that the provoked pathoimmunological reaction such as
      antiphospholipid antibody syndrome during the treatment for meningitis needs to
      be cared during the course of SLE.

PMID- 11517490
TI  - [A case of slowly progressive "pharyngeal-cervical-brachial variant of Guillain
      Barre syndrome (PCB)"].
AB  - A 69-year-old woman was admitted to our hospital because of slowly progressive
      weakness in the neck, shoulders, proximal arms, oropharyngeal muscles. From a
      viewpoint of clinical course and signs, it was suspected that the patient was
      suffered from motor neuron disease. However, serial electrophysiological studies
      showed the existence of local demyelination of the motor nerves. The
      immunoadsorption was then performed and marked recovery of symptoms was obtained.
      In this case, we could not detect any established anti-ganglioside antibodies
      which was related to pharyngeal-cervical-brachial variant of Guillain-Barre
      syndrome(PCB) or Guillain-Barre syndrome (GBS). It is suggested that unknown anti
      ganglioside antibody may play an important role in cases of PCB. Despite of
      atypical slowliness of clinical progression and negative results of immunological
      studies, this patient is considered to be suffered from PCB, because of the
      results of electrophysiological studies and effectiveness of immunoadsorption
      therapy. Accordingly it may be important to take the possibility of PCB into
      diagnostic consideration, whenever the patient shows slowly progressive weakness
      in proximal arms, oropharyngeal muscles.

PMID- 11517491
TI  - [Two adult cases of nemaline myopathy presenting different clinical symptoms and
      CT findings].
AB  - We report herein two cases of nemaline myopathy which showed peculiar muscle
      involvement and clinical symptoms. Case 1: A 44-year-old woman had developed
      gradual woresening of muscle weakness. Neurologically, only flexion of her neck
      was found to be weak. Her muscular CT revealed mild atrophy of four extremities
      and the sternocleidomastoid muscles. Histological examinations with Gomori
      trichrome staining revealed tiny structures whose form was compatible with
      nemaline rods. Moreover, electronmicroscopic examination demonstrated the lattice
      pattern of electron-dense structures, and they also appeared to possess
      structural continuity with the Z-band. Case 2: A 56-year-old woman visited our
      department because of neck pulsations. Neurological examinations revealed
      bilateral hearing disturbance, marked atrophy of neck muscles, muscle weakness in
      four extremities and hypoactive deep tendon reflexes. She also exhibited steppage
      and waddling gaits. Her muscular CT demonstrated degenerative processes in the
      neck muscles(splenius muscles and semispinal muscles), trapezius muscles, para
      spinal muscles, deltoid muscles and gluteal muscles. Among them, the para-spinal
      muscles and extensor muscles of the lower limbs showed marked degeneration and
      had been partly replaced by fatty tissues. A muscle biopsy was performed, and the
      presence of nemaline rods was confirmed by Gomori-trichrome staining. Although
      these two cases could be diagnosed as nemaline myopathy, the clinical symptoms
      and muscular CT findings were not quite the same. Whether these differences might
      simply indicate different clinical phases during the disease progression or be of
      further pathogenic significance still remains unclear. Additionally, since long
      term follow-up studies of nemaline myopathy are quite rare, further follow-up
      examinations of these cases are necessary in order to understand the clinical and
      pathological alterations of nemaline myopathy.

PMID- 11517492
TI  - [An autopsied case of presenile dementia with tangles].
AB  - We report an autopsied case of presenile dementia showing neuropathologically
      abundant neurofibrillary tangles(NFT) without senile plaques(tangle only
      dementia). A Japanese woman developed memory disturbance when she was 60 years
      old. At age of 65, her ability to understand deteriorated and euphoria and
      wandering manifested but neither psychotic symptoms, including hallucination and
      delusion nor a change in character were observed. The patient was hospitalized at
      age 66 and a cranial CT scan revealed bilateral moderate atrophy of the cortex
      and moderate enlargement of the lateral ventricle, especially in the inferior
      horn. No lobar atrophy was detected. She exhibited an oral tendency and became
      appallic at her final stage and died at the age of 75. Autopsy showed that her
      brain weighed 850 g and neuropathological study showed numerous NFT mainly in the
      entorhinal (trans-entorhinal) region, subiculum, CA1-CA4, dentate gyrus,
      amygdara, subthalamic nucleus, basal nucleus of Meynert, substantia nigra and
      locus coeruleus. Severe neuronal loss with gliosis was noted in the temporal
      lobes including the hippocampal region. No senile plaque was detected in any of
      the brain regions. There have been some recent reports of patients with abundant
      NFT with the predominant involvement of the allocortex but no or very little
      senile plaque. All the patients in the reported cases were very elderly at
      onset(over 80 years of age). In our case, the onset was presenile and we could
      exclude any other diseases, that usually present with NFT, and to our knowledge,
      this is the first report of a presenile dementia with tangles.

PMID- 11517493
TI  - [Regional cerebral blood flow values measured by Xe-CT during the attack of
      transient global amnesia: a case report].
AB  - A 50-year-old right-handed woman was referred to our hospital for further
      examination of sudden global amnesia. The patient had no history of epilepsy,
      head injury or cerebral vascular diseases. There were no neurological deficits
      except for recent memory disturbance. We examined her cerebral blood flow(CBF)
      immediately during transient global amnesia(TGA) by stable xenon enhanced CT
      scans(Xe-CT) and twice thereafter. Xe-CT during the attack showed a significant
      diminution of regional blood flow from the right posterior temporal lobe to the
      occipital lobe. Conventional MRI scans also had been performed serially but it
      could not detect the local ischemic event. The ischemic lesion was clearly
      divided and larger than those cases reported using PET, SPECT, and diffusion
      weighted MRI. TGA happens suddenly, and recovery is immediate. It becomes very
      difficult to study CBF during TGA attack. However stable Xe-CT is capable of
      examining CBF easily, so we concluded that CBF examination by Xe-CT in TGA
      patients would be helpful to reveal the mechanism of TGA.

PMID- 11517494
TI  - [A case of Marchiafava-Bignami disease caused by anorexia nervosa].
AB  - A 29-year-old female without alcoholism whose height and weight were 152 cm and
      28 kg had complained of severe anorexia since about 10 years ago. The splenium of
      the corpus callosum showed symmetrically low-intensity area in T1 WI and high
      intensity area in T2 WI on her brain MRI. These findings could be reversible by
      the recovery of her nutritional condition. The findings of neurological and
      neuropsychological examinations were normal. To our knowledge, this is the first
      case report of Marchiafava-Bignami disease caused by Anorexia Nervosa.

PMID- 11517496
TI  - [Placement of stent for internal carotid artery stenosis in the cervical portion
      improved ocular ischemic syndrome].
AB  - We report a case of ocular ischemic syndrome due to severe stenosis of the
      internal carotid artery. The patient was a 67-year-old man with a hemispheric
      transient ischemic attack and an amaurosis fugax. Ocular examination showed
      multiple soft exudates and dilatation of the retinal veins. Carotid stenting was
      performed to reconstruct the internal carotid artery. The multiple soft exudates
      were almost diminished and the visual acuity was improved. These results suggest
      that carotid stenting for severe stenosis of the internal carotid artery should
      be one of the less invasive methods to improve the microcirculation of the
      retina.

PMID- 11517495
TI  - [Repeated vertebrobasilar ischemic stroke caused by an intracranial vertebral
      artery dissection not detected on the initial angiogram: a case report].
AB  - Spontaneous dissection of the intracranial vertebral artery has been increasingly
      recognized as a cause of vertebrobasilar ischemic stroke. However, little is
      known about its natural history and clinical course. The authors report a young
      patient with repeated cerebral infarction in the posterior cerebral circulation
      caused by dissection of the vertebral artery, which was not detected on the first
      angiogram. The otherwise healthy 22-year-old male suddenly developed visual
      disturbance. Neuroradiological examination revealed right occipital infarction,
      but cerebral aniography revealed no caliber change or other pathological
      findings. He was treated with antiplatelet therapy. Two years later, he suffered
      vertigo, nausea, and dysarthria due to newly developed left cerebellar and
      medullary infarction. Cerebral angiography revealed left vertebral artery
      occlusion. T1-weighted MR image demonstrated Gadlinium-enhanced intramural
      hematoma in the occluded left vertebral artery, which was compatible to the
      arterial dissection. The present case argues serial neuroimaging studies
      especially in young patients with vertebrobasilar stroke in order to rule out the
      arterial dissection, even if initial angiography failed to demonstrate any
      radiographical evidence.

PMID- 11517497
TI  - [Lateral thoracic meningocele].

PMID- 11517498
TI  - [A parent and a child cases of autosomal dominant spinocerebellar degeneration:
      high signal intensity in the transverse pontine fibers(cross sign)].

PMID- 11517499
TI  - [Chronic subdural hematoma with spontaneous intracranial hypotension].

PMID- 11517500
TI  - [Linkage of gene expression with cerebral vasospasm].

PMID- 11517501
TI  - [Surgical anatomy and techniques of carotid endarterectomy without shunt].

PMID- 11517502
TI  - [Treatment for brain metastasis from lung cancer in the era of radiosurgery].
AB  - OBJECTIVE: The treatment for brain metastasis has undergone remarkable changes
      since the development of radiosurgery. We investigated the results of treatment
      for brain metastasis from lung cancer since the initiation of gamma knife
      radiosurgery (GKRS) and we discuss the usefulness of GKRS combined with other
      treatments in cases with recurrence. METHODS: We treated 142 patients with brain
      metastasis from lung cancer. Sixteen patients were treated surgically, 11
      patients were treated with whole brain radiation therapy (WBRT), and 115 patients
      were treated with GKRS. Our treatment plan is to use GKRS in cases with less than
      5 lesions and lesions less than 3 cm in mean diameter. We use WBRT in cases with
      5 or more lesions, and surgery in cases with lesions 3 cm or larger. If new
      lesions or tumor regrowth appeared after the initial treatment, we retreated them
      with one of the methods mentioned above. RESULTS: Twice or three-time treatments
      were performed in 30 patients. Median survival including all cases was 10 months
      and the number of deaths due to local treatment failure was only 5 (6.5%) out of
      the total 77 deaths which occurred. CONCLUSION: We were able to carry out less
      invasive treatment for brain metastasis from lung cancer by utilizing GKRS.
      Though we have to consider the indications for other treatments, we can say that
      radiosurgery is usually the treatment of first choice for brain metastasis from
      lung cancer. When new lesions appear in cases where a particular initial
      treatment was used, it is possible to maintain or improve the quality of life by
      retreatment, using a combination of GKRS, surgery or WBRT, to prolong the
      patient's life.

PMID- 11517503
TI  - [Chemotherapy for gliomas based on the expression levels of drug resistant
      genes].
AB  - Drug resistance, which often occurs during chemotherapy, is still a great
      obstacle to the success of human malignancy treatment. Among many possible
      mechanisms of drug resistance (biological, biochemical, kinetic or
      pharmacological), both typical and atypical multidrug-resistance (MDR) have been
      extensively studied. We picked up MDR-1, MXR, MRP1, MRP2, TopoII alpha, MGMT, and
      GST-pi as drug-resistant gene, based on experimental data and previous reports.
      Expression of these genes were measured in 14 malignant glioma specimens by
      reverse transcription polymerase chain reaction assay. We chose anticancer drugs
      for each patient, based on results of drug resistant gene expression to acquire
      good response to drugs. Though our follow-up periods are not long enough to
      analyze the results of our chemotherapy, 78% (7/9) of our glioma patients who
      were treated with our chemotherapy are free from tumor progression. The assays,
      which measure the expression of drug resistant genes, are necessary to allow
      rapid detection of the drug-sensitivity to chemotherapy in malignant glioma
      patients.

PMID- 11517504
TI  - [Study of lymphocyte and NK cell activity during mild hypothermia therapy].
AB  - Infectious disease is a common complication of mild hypothermia therapy. However,
      very little has been reported about immune response during hypothermia. In the
      present study, the number and subset of peripheral lymphocytes and mitogen
      response to phytohaemagglutinin (PHA) and concanavalin A (Con-A) were examined in
      14 patients who received mild hypothermia therapy. NK cell ratio and activity
      were also examined in the same patients. Six out of 14 patients had complicated
      infectious diseases during mild hypothermia therapy. Five of them had pneumonia
      and the remaining one had thrombophlebitis. The number of peripheral lymphocytes
      decreased in patients whose rectal temperature was less than 34.5 degrees C,
      whereas mitogen response of lymphocytes to PHA and Con-A remained unchanged in
      patients whose rectal temperature was above 34.0 degrees C. NK cell ratio and
      cytotoxicity decreased in patients whose rectal temperature was less than 34.5
      degrees C, including infectious cases. These results suggested that, under
      hypothermia therapy, immune responses of the patients whose rectal temperature
      was less than 34.5 degrees C were disturbed because of the reduced number of
      peripheral lymphocytes and depression of NK cell activity.

PMID- 11517505
TI  - [Schwannoma of the cervical spinal cord with cervical angina: a case report].
AB  - A case of schwannoma of the cervical spinal cord presenting with cervical angina
      is reported. A 49-year-old man was admitted to our hospital with severe chest
      pain, cold sweats, and unconsciousness. Extensive cardiac examination showed no
      abnormal findings. Neurological deficits were muscular weakness and atrophy of
      the left arm, bilateral hypersthesia of the arms, and hyporeflexia of the left
      biceps. MRI revealed a tumor in the left side of the spinal canal between C4 and
      C5. The diagnosis was neurinoma of the left nerve root in C5. The tumor was
      completely removed surgically by laminectomy. Surgery confirmed that the tumor
      had originated from the left posterior root of C5 and that, histologically, it
      was schwannoma. The severe chest pain immediately disappeared after removal of
      the tumor with only dull post-operative chest pain remaining. We hypothesized
      that the severe chest pain was protopathic pain caused by compression of the
      anterior C5 root by the tumor and/or disturbance of the inhibitory pain
      mechanisms of the sympathetic nerve located in the posterior horn of the spinal
      cord. It must be kept in mind that cervical angina caused by spinal schwannoma is
      one of the differential diagnoses of chest pain.

PMID- 11517506
TI  - [Brown-Sequard syndrome and cervical CSF leakage due to a knife injury: a case
      report].
AB  - We report a case of Brown-Sequard syndrome and cervical CSF leakage caused by a
      knife injury. A 34-year-old man was involved in a fight and was stabbed on his
      occiput and back with a knife. Neurological examination on admission showed right
      hemiparesis, right hemihypesthesia and left hemihypalgesia, indicating Brown
      Sequard syndrome. Furthermore, cerebrospinal fluid was leaking from the occipital
      stab wound. Head CT scan showed massive accumulation air in the subarachnoid
      space. Cervical MRI showed that the injury tract reached to the space between the
      occipital bone and the atlas. One week after admission, suboccipital craniectomy
      and duraplasty were performed because of continuous CSF leakage. Although, the
      CSF leakage recurred due to the wound infection, it disappeared naturally as the
      patient's general condition improved. Follow-up MRI studies demonstrated the
      cervical spinal lesion as hyperintensity on T2WI, which localized at the right
      side of the spinal cord. The patient's hemiparesis gradually improved and he
      underwent rehabilitation. Spinal cord injury due to a stab wound by a knife is
      rare in Japan. In this case, we suppose that the mechanism of spinal cord injury
      was due to direct injury by a knife avoiding the lateral corticospinal tract
      because his right hemiparesis obviously improved.

PMID- 11517507
TI  - [A case of thrombosed arteriovenous malformation in the brain stem].
AB  - A rare operative case of thrombosed arteriovenous malformation (AVM) in the brain
      stem was reported focusing on its differential diagnosis from cavernous
      malformation. A 49-year-old woman had developed pontine hemorrhage twice during
      the last two years. She was diagnosed by neurologists as having cavernous
      malformation in the brain stem, and then referred to our institute. Neurological
      examinations showed left hemi motor and sensory disturbance, right abducent palsy
      and right auditory disturbance. A computed tomography (CT) scan revealed a high
      density mass in the brain stem considered as a hematoma with slight enhancement.
      Magnetic resonance imaging (MRI) revealed a high intensity mass in T1 and T2
      weighted MRI with marginal hemosiderin rim, but neither flow void sign nor
      enhancement effect was detected. Angiography depicted no abnormal vasculature in
      the posterior fossa. The patient underwent surgical resection of the lesion 43
      days after a second hemorrhage. Midline sub-occipital craniotomy and the
      infrafacial route were chosen. Surgery was troubled by arterial bleeding, and
      pathological examination revealed a thrombosed AVM. She newly developed right
      facial palsy, right abducent palsy and disturbance of right conjugate gaze, but
      she is recovering step by step. Although the radiological feature of thrombosed
      AVM in the brain stem is similar to that of cavernous malformation, the operative
      procedure for thrombosed AVM is very difficult due to aggressive arterial
      bleeding that easily leads to surgical injury in the small surgical corridor in
      the brain stem. We reported a rare case that was pathologically well identified
      as thrombosed AVM in the brain stem focusing on its differential diagnosis and
      surgical treatment.

PMID- 11517508
TI  - [Intravascular lymphomatosis: a case report].
AB  - We report a case of a 64-year-old man with intravascular lymphomatosis. He had
      dementia and generalized seizure. Computed tomogram scan and magnetic resonance
      imaging showed multiple infarctions in the right frontal lobe, right cerebellar
      hemisphere and left occipital lobe. A month after admission he had a daily high
      fever and frequent convulsions. The level of serum LDH was progressively getting
      higher and the level of beta 2-microglobulin in both serum and CSF was high. One
      and a half months after admission we performed an open biopsy for making a
      definite diagnosis by pathological examination. Histological diagnosis was
      intravascular lymphomatosis (angiotrophic lymphoma) of large B cell type. He was
      treated with regimens of combined chemotherapy with M-CHOP (methotrexate,
      cyclophosphamide, adriamycin, vincristine, prednisolone). After chemotherapy his
      consciousness was gradually improving better and the level of serum LDH and beta
      2-microglobulin was reduced to a low level. Three months after admission he died
      of respiratory failure. After a review of the literature and experience with this
      case, it is obrious that early diagnosis of this disease is difficult. However,
      we think that multiple cerebral infarctions on neuroradiological examinations and
      high levels of serum LDH (especially LDH2 and LDH3) and beta 2-microglobulin in
      CSF and serum should lead to a presumptive diagnosis of this disease, and biopsy
      should be used to make a difinite diagnosis.

PMID- 11517509
TI  - [Surgery of anterior communicating artery aneurysms with the perforating artery
      branching from the dome].
AB  - The authors have treated two cases of anterior communicating artery aneurysms
      with the perforating artery branching from the top of the dome. Case 1 was a 32
      year-old female. She developed sudden-onset of headache while sleeping.
      Angiography showed an anterior communicating artery aneurysm with its dome
      directed upward. The left pterional approach was utilized, and a rather thick
      perforating artery was found branching from the top of the dome and going upward.
      Neck clipping of the aneurysm was performed resulting in interruption of the
      blood flow of the perforating artery. The patient showed no neurological deficit
      postoperatively. Case 2 was a 67-year-old female. She suffered from sudden-onset
      of headache and was transferred from another hospital to the author's care. Three
      dimensional CT angiography revealed an anterior communicating artery aneurysm
      with its dome directed in the anterior-superior direction. A rather thick
      perforating artery was coming off the top of the dome. Neck clipping was carried
      out, but permanent memory impairment appeared postoperatively. The perforating
      arteries coming off the anterior communicating artery have been called the
      hypothalamic arteries. In 1994, Serizawa et al divided these arteries into three
      groups. One is the subcallosal artery, which gives blood flow not only to the
      hypothalamus but also to the subcallosal area. The other two are the hypothalamic
      and chiasmatic arteries. The authors consider that this nomenclature of those
      arteries is suitable in practical use for surgery, because these arteries have
      different vessel sizes, they originate from the anterior communicating artery,
      and supply different territories with blood. Since the septal nuclei are in the
      subcallosal area, interruption of blood flow of the subcallosal artery by the
      clipping of an aneurysm may result in memory impairment caused by damage to the
      septal nuclei. Serizawa et al also reported that some branches are coming from
      the A2-segment to the subcallosal area as collateral circulation. In the author's
      two cases, the perforating arteries branching from the top of the domes were
      considered to be subcallosal arteries, because their size was rather thick and
      the arteries were going upward directed probably to the subcallosal area. Memory
      impairment in case 2 was considered a natural outcome due to the interruption of
      blood flow of the subcallosal artery by the clipping of the aneurysm. On the
      other hand, in case 1, sufficient collateral blood flow from A2 to the
      subcallosal area might have prevented damage to the septal nuclei, probably
      because of the insufficient size of the subcallosal artery. In these rare cases,
      dome clipping and coating should be the first choice of treatment, because
      prognosis after dome clipping of the aneurysm with coating was rather
      satisfactory.

PMID- 11517510
TI  - [A case showing effective radiotherapy for a radiation-induced glioblastoma].
AB  - Radiation-induced glioblastoma is usually resistant to all treatments. We report
      a case with radiation-induced glioblastoma, in which radiotherapy was remarkably
      effective. A 14-year-old female with a history of acute lymphoblastic leukemia,
      at the age of 7, underwent 15 Gy of radiotherapy to the whole brain. She was
      admitted to our department due to the development of headache and nausea.
      Magnetic resonance imaging showed an irregularly enhanced mass in the left
      frontal lobe. Partial removal of the mass was performed and histological
      examination showed it to be glioblastoma with a high MIB-1 index. The patient
      underwent 40 Gy of local radiotherapy and chemotherapy with ACNU and Interferon
      beta for 2 years. The residual tumor disappeared after the radiotherapy, and her
      status is still "complete remission", 29 months after the onset.

PMID- 11517511
TI  - [A case of suprasellar hemangioblastoma with thoracic meningioma].
AB  - Supratentorial hemangioblastoma is encountered very rarely, with only about 110
      cases reported. This report concerns a case of a suprasellar hemangioblastoma
      associated with thoracic meningioma. A 62-year-old man was admitted with visual
      disturbance of the left eye. T2-weighted magnetic resonance imaging (MRI) showed
      a high signal intensity mass in the suprasellar region without perifocal edema.
      T1-weighted MRI with gadolinium showed a homogeneously enhanced mass. The
      angiogram revealed remarkable tumor staining originating from the right and left
      internal carotid arteries (ICA) and the left external carotid artery (ECA). On
      the basis of the pre-operative diagnosis of tuberculum sellae meningioma, total
      tumor removal was performed. Photomicrographs of the specimen showed numerous
      capillaries divided by stroma cells. Positive immunostaining for factor VIII
      related antigen (F VIII RAg) was observed in endothelial cells, but
      immunostaining for epithelial membrane antigen (EMA) was not observed in any
      cells. A diagnosis of suprasellar hemangioblastoma was made on the basis of these
      findings. The patient suffered paraparesis on the postoperative seventh day.
      Since MRI showed a thoracic tumor, a second total tumor removal was performed.
      The tumor was diagnosed as a meningothelial meningioma. The patient was
      discharged without evidence of new neurological deficits. Our experience shows
      that, when a mass is vascularized in the cerebral hemisphere, the possibility of
      hemangioblastoma needs to be taken into consideration.

PMID- 11517512
TI  - [Gene therapy for rheumatoid arthritis].

PMID- 11517513
TI  - [Cytokine production by peripheral blood mononuclear cells in bronchial asthma
      treated with suplatast tosilate].
AB  - Supratast tosilate is a newly developed 'anti-allergic' drug and it has been
      shown to suppress cytokine production by type-2 helper T cells (Th2) in vitro.
      However, it is unclear whether a similar inhibitory effect on Th2 cytokines
      production is produced iv vivo. To elucidate the actions of the in vivo
      mechanisms of this drug, we isolated peripheral blood mononuclear cells (PBMCs)
      from 10 atopic asthmatics treated with supratast tosilate and investigated the
      capacity for cytokine production ex vivo. Interleukin (IL)-5 production by PBMCs
      stimulated with the combination of phorbol myristate acetate and ionomycin were
      reduced significantly 6 or 12 weeks after the treatment with supratast tosilate.
      In contrast, no significant reduction was seen in IL-4 or Interferon (IFN)-gamma
      production. The peripheral blood eosinophil count and weeks, but no significant
      difference was sees in total IgE levels. Both morning and evening peak expiratory
      flow were significantly elevated after 6 weeks. These results suggest that
      supratast tosilate improves the disease status of bronchial asthma through its
      ability to inhibit the production Th2 cytokines, at least IL-5, in vivo.

PMID- 11517514
TI  - [Experience of specific immunotherapy with standardized Japanese cedar pollen
      extract].
AB  - A study was conducted in 165 subjects with Japanese cedar pollinosis (JC) to
      evaluate the switching to the new standardized extract (SE) for patients who are
      going on specific immunotherapy (SP-IT) with conventional non-standardized
      extracts, products of Trii Co. or Hollister-Stier Co. Eight of 137 subjects
      exhibited adverse systemic reactions such as general skin eruption and despnea
      when JC allergen extract of Hollister-Stier Co. was switched to JC-SE. There were
      6 cases where concentration of the extract had to be decreased due to
      extraordinary late reactions, while none of 28 subjects exhibited adverse side
      effect, when conventional allergen extract by Torii Pharmaceutical Co. was
      switched to JC-SE. Careful switching to high concentration of SE is required,
      because eight cases with adverse side effect were shown in switching to 200
      JAU/ml and 2000 JAU/ml. 20 subjects started with SP-IT by JC-SE after spread of
      JC in the year of 2000 exhibited no adverse side effects in our protocol.

PMID- 11517515
TI  - [Chronotherapy of bronchial asthma: circadian rhythms in asthmatic symptoms.
      Report I: Survey on chronobiology acrophase of asthmatic symptoms].
AB  - We conducted a questionnaire survey on the onset time and frequency of asthmatic
      symptoms in adults with bronchial asthma who were regular clinic attendees in 17
      sites in Chiba Prefecture, and analyzed 513 respondents. As a result, the
      frequency of wheezing was 54.6%, the highest of all symptoms. Feeling of chest
      discomfort was 32.2%, followed by asthma attack (13.8%), cough (8.7%) and dynpnea
      (6.8%). Asthmatic symptoms were highest from midnight to early morning, with the
      peak at around 4 o'clock am. The same pattern was seen regardless of the severity
      and types of asthma. This survey also showed that conventional anti-asthmatic
      therapies decreased the frequency of nightly asthmatic symptoms from the
      baseline: 7 times or more per week reduced from 44.9% to 16.1%, 3 times or more
      per week from 76.8% to 40.4%, and at least once per week from 94.4% to 71.5%. The
      results suggest that it is important to take another therapeutic strategy, which
      can administer medications at the appropriate time according to the circadian
      rhythms in asthmatic patients to better control asthma.

PMID- 11517516
TI  - [Japanese cedar pollen in house dust].
AB  - Caring for oneself against Japanese cedar pollinosis is important as well as
      receiving medical-care. Although the importance of avoiding pollen is described
      in the guideline for nasal allergy medical treatment, however, there is no
      information for effective dust cleaning for the home. This study examined how
      many cedar pollens were included in indoor dust in order to obtain basic data
      whether dust removal for cedar pollen is available for pollinosis suffers. As a
      result, the study found that there were many Japanese cedar pollens in indoor
      dust even before the pollen season. Cedar pollen increased with the increasing
      number of airborne pollen. The highest number of pollen found in one week was
      approximately 450 pollens in a square meter of a living room floor. The study
      concluded that cleaning is one of the best way to remove Japanese cedar pollens
      found in indoor dust.

PMID- 11517517
TI  - [Correlation between the clinical effects of Seratrodast and the level of 11
      dehydrothromboxane B2 in urine/sputum in bronchial asthma patients].
AB  - Seratrodast, an antagonist to thromboxane A2 (TXA2) receptors, is not always
      effective in patients with bronchial asthma. In fact, some respond definitely to
      this drug while others not. In the present study, to clarify the predictability
      of the clinical effects of Seratrodast, we investigated whether there is a
      correlation between the levels of TXB2 and 11-DHTXB2, both of which are
      metabolites of TXA2, in urine and sputum taken before the administration and the
      clinical effects seen after initiation of the treatment. Baseline concentrations
      of TXA2 metabolites in urine/sputum were not significantly different between
      responders and non-responders. However, 4 cases who had remarkably responded to
      Seratrodast had significantly higher baseline 11-DHTXB2 levels than the rest of
      the patients. These results suggested that bronchial asthma patients with high
      urinary 11-DHTXB2 levels could markedly respond to Seratrodast treatment.

PMID- 11517518
TI  - [A case of food-dependent exercise-induced anaphylaxis (FDEIA) caused by wheat
      successfully induced by administration of aspirin and wheat].

PMID- 11517519
TI  - [Peak inspiratory flow rates attained by asthmatic patients through a dry-powder
      inhaler of fluticasone propionate].

PMID- 11517520
TI  - [A case of anaphylaxis caused by buck-wheat as an addition contained in pepper].

PMID- 11517521
TI  - [Long-term results of valve-retaining homograft and xenograft patch for
      transannular reconstruction of the right ventricular outflow tract in tetralogy
      of Fallot].
AB  - Thirteen patients with tetralogy of Fallot underwent reconstruction for
      hypoplastic right ventricular outflow tract using a preserved homograft or
      xenograft patch with single or double cusps. Homografts and xenografts preserved
      in 70% ethanol were implanted in 10 patients, and xenografts treated with
      glutaraldehyde were used in 3 patients. All the patients are doing well in their
      profession without one who died 18 years after operation. Valve-retaining
      homograft and xenograft patches provided excellent early hemodynamic function,
      but did not prevent pulmonary insufficiency late after the operation. Both
      homograft and xenograft cusps tended to degenerate several years after
      implantation, but cusp failure was not accompanied by outflow stenosis.

PMID- 11517522
TI  - [Long-term results of Rygg's monocusp ventricular outflow patch for the
      reconstruction of right ventricular outflow tract in tetralogy of Fallot].
AB  - Thirty surviving patients after corrective surgery for tetralogy of Fallot with
      right ventricular outflow tract reconstruction (RVOTR) using monocusp ventricular
      outflow patch (MVOP) were reviewed retrospectively to determine the long-term
      results. The age at operation ranged from 2 to 55 years with a mean of 19 years,
      and follow-up extended to 18.2 years (cumulative: 345.4 patient-year). There were
      4 late deaths (1.2% per patient-year), and the cumulative survival rate was 85.3%
      at 18 years after the corrective surgery. Eight patients (2.3% per patient-year)
      required intracardiac reoperations mostly resulted from problems after RVOTR with
      MVOP, such as recurrent stenosis of right ventricular outflow tract (3 cases) or
      pulmonary valvular incompetence (4 cases). In addition, one patient underwent
      balloon angioplasty for the recurrent stenosis located in the distal end of MVOP.
      Freedom from surgical or catheter reintervention for the MVOP-related
      complication was 60.6% at 18 years after the corrective surgery. MVOP caused
      compression of the pulmonary artery at the distal end of the anastomosis and
      reoperation in a younger patients quite early after the corrective surgery. Like
      other transannular patches, tissue failure and degeneration of MVOP were
      inevitable, and resulted in severe pulmonary valvular incompetence that required
      the valve replacement in 4 patients (1.3% per patient-year). Freedom from
      pulmonary valve replacement was 71.2% at 18 years after the corrective surgery.
      As long-term results, our experiences emphasize the need for an innovative
      transannular patch that possesses significantly better long-term durability.

PMID- 11517523
TI  - [Right ventricular outflow tract reconstruction with PTFE mono-cusped
      transannular patch for tetralogy of Fallot].
AB  - Conotruncal repair for tetralogy of Fallot consists of (1) precise closure of the
      VSD with the membranous flap and (2) reconstruction of the right ventricular
      outflow tract (RVOT) by a short transannular patch (< 30% of the RV length) with
      a wide PTFE monocusp. This report describes the mid-term results in 46 patients
      with tetralogy of Fallot who underwent conotruncal repair with PTFE monocusped
      transannular patch and have been followed up for 4 years or more. There was no
      early and late death and no patient required reoperation. No patient has had a
      significant residual defect or tricuspid regurgitation (> II). The right and left
      ventricular pressure ratio was 0.41 +/- 0.12 and the pressure gradient across
      RVOT was 10.5 +/- 5.9 mmHg, signifying sufficient relief of RVOT obstruction. The
      mobility of the PTFE monocusp was echocardiographically detected in 86% over a
      mean follow-up period of 84 +/- 34 months and % freedom from pulmonary
      regurgitation (> II) was 85.9% at 10 years postoperatively. Excellent long-term
      durability of the PTFE monocusp provided the normal right vent performance with
      RVEDV of 91.8 +/- 29.5% of normal and a central venous pressure of 5 +/- 1 mmHg.
      In conclusion, conotruncal repair with a wide and short transannular patch has
      provided good mid-term results with the excellent long-term durability of PTFE
      monocusp.

PMID- 11517524
TI  - [Two-cusp plasty using a pedicled auto pericardial patch for the right
      ventricular outflow tract in complete repair of tetralogy of Fallot].
AB  - BACKGROUND: Pulmonary stenosis (PS) and regurgitation (PR) are major concerns
      late after transannular patching for tetralogy of Fallot (TOF). In this study, we
      reviewed the TOF patients undergoing transannular patching to reveal whether the
      valvuloplasty technique (two cusp plasty) improved long-term results. We also
      reviewed potential for grow of the pedicled autopericardial patch. METHODS AND
      RESULTS: Since 1977, 151 patients underwent corrective surgery for TOF.
      Transannular patching was required in 58 (38.4%). PS and PR in the postoperative
      long-term period of these 59 cases were reviewed. 25 patients had the standard
      transannular patching (S-TAP), and 33 had two-cusp plasty (TCP). Pedicled
      autologous pericardial patch were used in 9 patients of TCP. Actuarial freedom
      from PS at 7 years was 70.8 +/- 9.2% in S-TAP and 79.2 +/- 8.3% in TCP, and there
      was no significant difference. Incidence of severe PR was significantly higher in
      S-TAP (7/24) than TCP (1/24) (p < 0.05). Actuarial freedom from PR at 7 year was
      69.6 +/- 9.6% in the former and 95.8 +/- 4.2% in the later, respectively. The
      diameter of the pulmonary arterial annuals was augmented with the somatic growth
      in 6 patients with the pedicled pericardial patch. CONCLUSIONS: Two cusp plasty
      was more effective to prevent PR in the postoperative long-term period, comparing
      to S-TAP. As the material of the patch, pedicled autologous pericardium showed
      satisfactory outcome.

PMID- 11517525
TI  - [Reoperation for obstructed extracardiac valved conduit after Rastelli
      operation].
AB  - Between July 1988 and November 2000, 61 patients who were 11.3 +/- 3.8 years old
      underwent reoperation for obstructed extracardiac valved conduit at 7.0 +/- 2.1
      years after Rastelli operation. The right ventricular outflow tract was
      reconstructed with nonvalved (n = 36) or valved (n = 9) conduit and Danielson's
      procedure (n = 16). One patient who underwent Danielson's procedure and
      concomitant aortic valve replacement died in 7 days after reoperation. Mean
      systolic pressure gradient across the right ventricular-pulmonary artery
      decreased from 58.6 mmHg to 14.6 mmHg. Re-reoperation was performed in 6 patients
      after Danielson's procedure for restenosis caused by contracture of xenograft
      outflow patches. There is no re-reoperation in patients with nonvalved conduit
      replacement. Postoperative pulmonary regurgitation by UCG was moderate in 12
      patients with nonvalved conduit replacement and two with Danielson's procedure.
      In our experience, reoperation for obstructed extracardiac valved conduit after
      Rastelli operation is safe and nonvalved conduit replacement provides good
      midterm results.

PMID- 11517526
TI  - [Reoperation for late postoperative right ventricular outflow tract obstruction].
AB  - Between February 1993 and July 2000, 18 patients with a mean age of 7.9 years
      underwent re-operation for critical stenosis of the right ventricular outflow
      tract. Their diagnoses of these patients included tetralogy of Fallot (n = 7),
      transposition of the great arteries (n = 6), truncus arteriosus communis (n = 3),
      and double outlet right ventricle with pulmonary stenosis (n = 2). The first
      operations were extracardiac conduit operations (n = 9), arterial switch
      operations (n = 6) and patch reconstruction of the right ventricular outflow
      tract (n = 3). At re-operation, the right ventricular outflow tract obstruction
      was released completely and reconstructed using a monocusp ventricular outflow
      patch (n = 14), valved pericardial roll (n = 2), or bovine pericardial patch
      sparing the native pulmonary valve annulus (n = 2). There were no early deaths,
      although one patient died of arrhythmia 2.6 years after re-operation. The
      pressure gradient across the right ventricular outflow tract, right ventricular
      systolic pressure, and right ventricle to systemic systolic pressure ratio were
      satisfactorily relieved (84.3 +/- 19.0 vs. 16.7 +/- 19.7 mmHg, 109.2 +/- 20.5 vs.
      48.7 +/- 16.7 mmHg, 0.92 +/- 0.25 vs. 0.43 +/- 0.16; p < 0.001, p < 0.001, p <
      0.001, respectively). The right ventricular end-diastolic volume index and right
      ventricular ejection fraction were also improved (166.3 +/- 85.2 vs. 105.6 +/-
      28.8% of normal, 38.3 +/- 12.6 vs. 50.9 +/- 8.8%; p < 0.05, p < 0.005,
      respectively). Re-operation should be done before the development of marked right
      ventricular dysfunction, while it can still be performed at a low risk with
      satisfactory results.

PMID- 11517527
TI  - [Surgical techniques and results of right ventricular [correction of venericular]
      outflow tract reconstruction with pedicled autologous tissue].
AB  - From 1987 to 2000, 44 patients underwent anatomic repair of anomalies with
      pulmonary outflow obstruction by using pedicled autologous tissue in
      reconstructing the pulmonary outflow tract. Twenty-four patients had tetralogy of
      Fallot with pulmonary atresia (TOF/PA), from 1.7 years to 12.9 years of age (mean
      9.0 years). In the group of TOF/PA, slit-widening method was performed in 22,
      autologous pericardial flap was used in 1, and atrial appendage was used in 4
      patients. Eight patients had transposition of the great arteries with ventricular
      septal defect and pulmonary stenosis (TGA type III), from 9 months to 9.2 years
      of age (mean 4.5 years). All of the patient with TGA type III under went direct
      PA-RV anastomosis (natural route non-conduit repair). Three patients had truncus
      arteriosus, from 1 month to 7.8 years of age (mean 4.5 years). In the group of
      the truncus, atrial appendage was used in 1 and direct PA-RV anstomosis was made
      in 2 patients. Six patients had Rastelli's conduit obstruction, from 6.6 years to
      20.3 years of age (mean 13.9 years). The conduit was removed and outflow tract
      was reconstructed with direct PA-RV anastomosis in 5 and using atrial appendage
      in 1 patients. There was one hospital death (2%) and no late deaths. In 31
      patients whose follow-up time exceed 5 years, 7 patients (23%) were found to have
      pressure gradient more than 40 mmHg at the pulmonary outflow tract. None of the
      patients with TGA who underwent natural route non-conduit repair developed late
      stenosis at the pulmonary out flow tract.

PMID- 11517528
TI  - [Right ventricular outflow tract reconstruction for pulmonary atresia with
      ventricular septal defect: the possibility of ventriculo-arterial direct
      anastomosis].
AB  - Between September 1997 and December 2000, 29 patients with pulmonary atresia
      associated with ventricular septal defect were undergone corrective surgery. The
      age at operation ranged from 24 days to 14.7 years. The 5 patients were younger
      than 3 months. The body weight at operation ranged from 1.5 kg to 35.8 kg. 10
      patients had MAPCAs. 21 patients had been undergone modified Blolock-Taussig
      shunt and/or uniforcalization of pulmonary artery (PA). We could perform right
      ventricular outflow tract reconstruction with ventriculo-arterial direct
      anastomosis in 19 patients (65%) (4/10; patients with MAPCAs, 3/5; younger than 3
      months). We performed pulmonary angioplasty on stenotic and/or underdeveloped
      leasions as a concomitant procedure in 13/19 cases. Our technique is composed of
      4 points, (1) fully mobilizing central and distal pulmonary artery (PA), (2)
      dissecting the PA with connective tissue together, (3) pulmonary arterial wall
      flap, (4) right ventricular outflow tract reconstruction during cardiac arrest.

PMID- 11517529
TI  - [Reconstruction of the pulmonary outflow tract without external conduit].
AB  - Between October 1987 and December 2000, 50 patients underwent reconstruction of
      the pulmonary outflow tract without external conduit. The primary malformation
      was tetralogy of Fallot with pulmonary atresia in 37, double outlet of right
      ventricle in 4, corrected transposition of the great arteries in 4, transposition
      of the great arteries with ventricular septal defect and pulmonary stenosis in 4,
      and double outlet of left ventricle in 2. Mean age at operation was 7.2 years,
      and mean body weight was 18.3 kg. To reconstruct posterior wall of the pulmonary
      outflow tract, interposition of autologous pericardium was performed in 24,
      direct anastomosis between pulmonary trunk and ventriculotomy in 13, longitudinal
      incision from ventriculotomy through pulmonary trunk in 12, and interposition of
      left atrial appendage in 1. Anterior wall was reconstructed with monocusp valved
      outflow patch (MVOP). There was one hospital death and no late death. At 10
      years, the freedom from reoperation for pulmonary outflow tract obstruction was
      100%, and freedom from reoperation for any cause was 86.6%. Transcatheter
      stenting for peripheral pulmonary stenosis was performed in 6 patients 2 to 10
      months after operation.

PMID- 11517530
TI  - [Right ventricular outflow tract reconstruction using monocusp valved outflow
      patch for pulmonary atresia with ventricular septal defect: influence of the
      presence of major aorto-pulmonary collateral arteries].
AB  - We have preferably utilized monocusp valved outflow patch (MVOP) for right
      ventricular outflow tract (RVOT) reconstruction in pulmonary atresia with
      ventricular septal defect (PA + VSD). The purpose of this study was to evaluate
      the influence of the presence of major aorto-pulmonary collateral arteries
      (MAPCAs) on probability of MVOP reconstruction and development of RVOT restenosis
      in midterm. 49 patients underwent complete repair (either MVOP reconstruction or
      Rastelli procedure) of PA + VSD in our service. These patients were divided into
      2 groups: group 1; 21 patients with MAPCAs, group 2; 28 patients without MAPCAs.
      There was one operative death (group 1). The probably of MVOP reconstruction was
      similar between group 1 and group 2 (71 vs 79%, p = 0.57, chi 2 test). Follow-up
      was completed for 48 survivors with the period ranged 3-108 months (mean 47
      months). In group 1, one patient died suddenly at home 10 months after surgery.
      For 47 long-term patients, the ratio of freedom from RVOT restenosis was 72% (95%
      CI: 52-92%, Kaplan-Meier method) at 5 year. There was no difference between 2
      groups (group 1; 73%, 95% CI: 45-100%, group 2; 74%, 95% CI: 48-99%,
      respectively, p = 0.85 by Log-Rank test). The presence of MAPCAs in PA + VSD was
      not a risk factor for either the probably of MVOP reconstruction or development
      of RVOT restenosis in midterm.

PMID- 11517531
TI  - [Intracardiac repair of tetralogy of Fallot with an anomalous coronary artery
      crossing the right ventricular outflow tract].
AB  - Between may 1993 and march 2001, 2 patients with tetralogy of Fallot and an
      anomalous coronary artery crossing the right ventricular outflow tract underwent
      intracardiac repairs. The anomalous coronary arteries included the left anterior
      descending from the right coronary artery (case 1), and the right coronary artery
      from the left coronary artery (case 2). In case 1, we turned down a flap of
      anterior wall of the main pulmonary artery, sutured it to the edge of the right
      ventriculotomy and placed a bicusped patch to the anterior aspect. In case 2, we
      underwent transpulmonary-transatrial repair and placed a transannular patch along
      by the left coronary artery. Right ventricular outflow tract reconstruction was
      successful in 2 cases.

PMID- 11517532
TI  - [Reconstruction of the right ventricular outflow tract in patients undergoing the
      Ross procedure].
AB  - Since 1992, 46 patients have undergone the Ross procedure. Of these, a pulmonary
      homograft was used for reconstruction of the RVOT in 16, and a tailored
      heterologous or autologous pericardial roll tube in 9. In the remaining 21, the
      autologous tissues were used as a posterior wall of the channel, placing another
      patch (bearing a monocusp in 14) anteriorly. All the patients survived the
      procedure. Reoperation has been needed thus far in one for infection of the
      prosthetic patch placed at the right ventricular outflow tract, and catheter
      intervention in 2 for mild obstruction across the channel. On the basis of
      postoperative catheterization, presence or absence of a valvar structure across
      the right ventricular outflow tract did not affect ejection fraction of the right
      ventricle and right atrial pressure. In contrast, right ventricular end diastolic
      volume was smaller, as well as diastolic pulmonary arterial pressure was higher,
      when a competent trifoliate valve was provided at the right ventricular outflow
      tract. An incision to the ventricular septum for subaortic stenosis, coronary
      arterial obstruction preoperatively present, and age at operation younger than 2
      years old, were unfavourable factors affecting right ventricular performance. We
      conclude that, in the majority of our patients, right ventricular performance was
      unlikely impaired even without a competent pulmonary valve. Use of a homograft,
      however, could be preferred in a selected group of patients with deleterious
      circumstances on the postoperative circulation.

PMID- 11517533
TI  - [The changes of the methods of the right ventricle outflow tract reconstruction].
AB  - There are many situation that we need to do some procedure for the right
      ventricle outflow tract reconstruction (RVOTR) among the congenital heart
      diseases. The procedures have changed during past decade. Also the changes have
      shown about the materials for outflow patches. We reviewed the changes through
      our experience. There were seventy-six cases or RVOTR from August, 1988 to
      December, 2000. Most of them were tetralogy of Fallot. Fifteen cases were done
      the Rastelli procedure. There were some other congenital heart diseases. The
      materials were mainly artificial in the period before 1995. Then it has been
      changed mainly to the autologous pericardium in the period after 1996. The sizes
      of the tract were made to match the standard of Rowlatt. We found some re
      stenosis and late mortality because of the pulmonary valve regurgitation. We are
      trying to reduce such complications.

PMID- 11517534
TI  - [Postoperative right ventricular function after repair of tetralogy of Fallot
      with respect to the method of right ventricular outflow tract reconstruction].
AB  - We evaluated postoperative right ventricular function in the sixty-four
      consecutive patients with tetralogy of Fallot underwent total correction. The
      patients were divided to three groups according to the method of right
      ventricular outflow tract reconstruction: transannular patching (TA group; n =
      31); right ventricular outflow patching with preservation of pulmonary valve ring
      (RV group; n = 12) and transatrial-transpulmonary approach without right
      ventriculotomy (no-RV group; n = 21). The early results of postoperative cardiac
      catheterization and echocardiography were compared among the three groups. Degree
      of pulmonary regurgitation was significantly low in the RV group and no-RV group
      compared with TA group (p < 0.005). Right ventricular ejection fraction was the
      highest in the no-RV group (p < 0.002). The repair without right ventriculotomy
      for tetralogy of Fallot can provide the best results with respect to
      postoperative right ventricular function.

PMID- 11517535
TI  - [Isoproterenol stress test for the evaluation of the residual stenosis of the
      right ventricular outflow tract].
AB  - Hemodynamic changes of the right side of the heart during isoproterenol stress
      test were assessed and analyzed in 36 patients who underwent definitive repair of
      tetralogy of Fallot or double outlet right ventricle with pulmonary stenosis.
      Patients having atresia of the pulmonary artery were excluded from the study. 24
      of the patients had previously undergone reconstruction of the right ventricular
      outflow tract (RVOT) with preserving the pulmonary valvar annulus (group N),
      whilst the remaining 12 patients had undergone transannular enlargement of RVOT
      with a patch (group T). Preservation of the pulmonary valvar annulus was
      determined when the intra-operative measurement of diameter of the pulmonary
      valvar annulus showed values greater than 90% of normal. In both groups, the
      isoproterenol infusion increased the right to left ventricular peak pressure
      (RVP/LVP) ratio, pressure gradient between the right ventricle and main pulmonary
      artery (RV-mPAP), and pressure gradient between the main pulmonary artery and
      peripheral pulmonary artery (m-pPAP). These values were significantly higher than
      those measured at rest. When comparisons were made between groups, RV-mPAP of
      group N was significantly higher than that of group T, both at rest and during
      stress test. By contrast, m-pPAP of group T was significantly higher than that of
      group N, both at rest and during stress test. Although no significant difference
      was found between the groups in RVP/LVP at rest and during stress test, RVP/LVP
      of both groups increased to the level of more than 0.6 after the isoproterenol
      infusion. These results led us to conclude that preservation of the pulmonary
      valvar annulus was better to be applied only to the patients who fulfilled our
      criterions. Additionally, in the setting of patch reconstruction of the pulmonary
      artery, every effort should be made so as not to leave the residual stenosis of
      the peripheral pulmonary artery.

PMID- 11517536
TI  - [Limited surgery for bronchogenic carcinoma].
AB  - In recent years limited operations including wedge resection, segmentectomy and
      simple lobectomy are getting increased as a treatment of choice for non-small
      cell lung cancer (NSCLC). However, surgery for lung cancer should be emphasized
      in terms of postoperative quality of life as well as complete resection or
      radical resection of the tumor. There have been few number of randomized
      controlled trials as to limited operation of lung cancer. Thus this kind of
      procedures such as wedge resection and segmentectomy for stage I NSCLC, and
      thoracoscopic lobectomy for stage I lung cancer, is not generally evaluated as an
      alternative treatment to the standard operation at the present time. In this
      paper current status of limited surgery for lung cancer is reviewed mainly based
      on recent literatures and results obtained from our experience in Institute of
      Development Aging and Cancer, Tohoku University.

PMID- 11517537
TI  - [A successful case report of emergency coronary artery bypass grafting for left
      main trunk obstruction with profound cardiogenic shock: bridge use of balloon
      pumping and percutaneous cardiopulmonary support system to surgical
      intervention].
AB  - A 73-year-old man was admitted for sudden onset of dyspnea with cardiogenic
      shock. Chest X-P showed bilateral severe pulmonary edema. Echocardiogram
      demonstrated diffuse severe hypokinesis of left ventricle. Emergency coronary
      angiography showed 99% stenosis of left main trunk with delay. After insertion of
      intraaortic balloon pump (IABP) and percutaneous cardiopulmonary support system
      (PCPS), vital signs and consciousness were improved. Emergency coronary artery
      bypass grafting (CABG) was performed, LIMA to left anterior descending artery,
      saphenous vein grafts to circumflex and right coronary artery. Left ventricular
      wall motion was improved after bypass grafting and cardiopulmonary bypass was
      weaned with catecholamine and IABP support. The patient was discharged from
      hospital 60 days after the operation with good cardiac function. We emphasized a
      usefulness of combined use of IABP and PCPS to provide systemic organ perfusion
      and reduce myocardial infarct size and ischemic damages after re-vascularization
      for coronary insufficiency with profound shock.

PMID- 11517538
TI  - [Translocation of the aortic valve for aortic stenosis in a patient with severe
      calcification in the aortic root: report of a case].
AB  - A 65-year-old woman was admitted to the hospital because of anterior chest pain.
      Computed tomography and transthoracic 2-D echocardiogram demonstrated aortic
      valvular stenosis with calcification of whole aortic root. Cardiac
      catheterization study showed a transaortic pressure gradient of 73 mmHg and
      coronary angiography showed 75% stenosis at the right coronary ostia. Aortic
      valve replacement and coronary artery bypass grafting were planned. At operation,
      sinotubular junction and bilateral coronary ostia severely calcified with
      stenosis, prompted us to translocate the aortic valve with the composite graft, a
      19 mm Bicarbon prosthesis and 25 mm woven Dacron graft. The postoperative course
      was uneventful. On cardiac catheterization done 27 days after operation,
      satisfactory valve motion and patent coronary bypass grafts were confirmed.

PMID- 11517539
TI  - [Case report of bioprosthetic mitral valve malfunction associated with right
      pulmonary embolism and heart failure].
AB  - The perioperative treatment of open heart surgery cases with preoperative
      pulmonary embolism is controversial. A 40-year-old woman, who had undergone
      mitral valve replacement with a bioprosthetic valve 16 years earlier, showed
      severe heart failure, right pulmonary embolism diagnosed by pulmonary perfusion
      scan in the subacute stage, and prosthetic valve regurgitation. Preoperative
      catheterization showed severe pulmonary hypertension of 122 mmHg, equal to the
      systemic pressure. Pulmonary angiography showed right peripheral pulmonary
      embolism without main pulmonary artery embolism. Prosthetic valve replacement
      with a BICARBON 27 M and tricuspid annuloplasty were performed, with thrombolytic
      therapy before and after operation without thrombectomy, because of pulmonary
      hypertension attributed to prosthetic valve regurgitation. Pulmonary perfusion
      scan and angiography showed improvement of pulmonary embolism after treatment.
      Postoperative catheterization showed good results, with right and left pulmonary
      artery pressure of 43/16(23) and 39/15(24) mmHg, mean pulmonary capillary wedge
      pressure of 4 mmHg, and cardiac index of 4.96 l/min/m2. It is important to make
      an early diagnosis of pulmonary embolism and treat the major cause of pulmonary
      hypertension in cases of cardiac valve disease with pulmonary hypertension.

PMID- 11517540
TI  - [Detection of visceral ischemia with doplex scanning method of mesenteric
      arteries: in patients with acute type B aortic dissection].
AB  - Between March, 1997 and January, 1999, 11 patients with acute type B aortic
      dissection underwent doplex scanning evaluation of mesenteric arteries for the
      early detection of visceral ischemia. Peak systolic velocity (PSV) of the celiac
      artery (CeA) and superior mesenteric artery (SMA) was measured on their
      admission. Mean PSV of CeA in the non-ischemic group (8 patients) and in the
      ischemic group (3 patients) was 1.66 +/- 0.34 m/sec and 3.60 +/- 0.49 m/sec (p =
      0.0481), respectively. Mean PSV of the SMA in the non-ischemic group and in the
      ischemic group was 1.93 +/- 0.52 m/sec and 3.33 +/- 0.37 m/sec (p = 0.00768),
      respectively. All patients with PSV of the mesenteric arteries above 3.00 m/sec
      presented visceral ischemia that required emergency operation. If PSV of the
      mesenteric arteries exceeds 3.00 m/sec, urgent surgical repair should be
      considered.

PMID- 11517541
TI  - [A case of lung cancer in which FDG-PET was useful for preoperative diagnosis].
AB  - The patient was 48-year-old woman. The patient was referred to our hospital due
      to detection of an abnormal shadow on a chest X-ray image during a health
      checkup. The results of a CT scan morphologically suggested a benign tumor, but a
      diagnosis could not be made even after bronchoscopic cytology. FDG-PET revealed
      accumulation at the tumor site suggestive of malignancy, and an operation was
      performed. Prompt pathological examination showed that the tumor was
      adenocarcinoma, and right lower lobectomy and lymphnode dissection were
      performed. FDG-PET is thought to be useful for diagnosis in cases of lung tumor
      in which a preoperative diagnosis can not be established.

PMID- 11517542
TI  - [A case of giant dumbbell shaped schwannoma with massive pleural effusion].
AB  - A 58-year-old female was admitted to the hospital complaining of dyspnea. The
      chest roentgenogram and CT scan revealed a large mediastinum tumor and massive
      pleural effusion in the right hemithorax. The diagnosis of lung cancer with
      carcinomatous pleulitis was performed through thoracocentesis an treatment of
      chemotherapy was chosen. After 6 years, she was admitted again to the hospital
      complaining of dull pain in the right leg. Chest CT scan and MRI showed a giant
      dumbbell shaped mass connected to the spinal canal. The tumor was larger than
      that of six years ago and diagnosed as schwannoma by CT-guided pericutaneous
      needle biopsy. At operation, hemilaminectomy of Th 1-3 was done first, and total
      tumor resection was performed through posterolateral thoracotomy. Intrathoracic
      adhesion was severe and it was difficult to control air leakage from the lung,
      thoracoplasty was performed.

PMID- 11517543
TI  - [Superior result of ketone body ratio in normothermic cardiopulmonary bypass].
AB  - Nineteen patients undergoing aortocoronary bypass surgery were divided into two
      groups according to the perfusion temperature, either normothermia (36 degrees C)
      or hypothermia (30 degrees C). The hepatic blood flow was measured at three
      points before, during and after cardiopulmonary bypass. Arterial and hepatic
      venous ketone body ratios (AKBR, HKBR) and hepatic venous saturation (ShvO2) were
      measured throughout the surgery. RESULTS: Hepatic blood flow in both groups was
      identical before, during, and after the CPB. The significantly lower ShvO2 levels
      were observed during the CPB in the normothermic group. The both AKBR and HKBR in
      the hypothermic group decreased severely after the initiation of CPB (p < 0.01).
      However, the reduction in AKBR and HKBR was less severe in the normothermic
      group. CONCLUSIONS: Normothermic CPB provides adequate liver perfusion and
      results in a better hepatic metabolism than hypothermic cardiopulmonary bypass.

PMID- 11517544
TI  - [Bacterial contamination of salvaged blood in open heart surgery: is that an
      airborne contamination or a normal skin flora contamination?].
AB  - We investigated sources of bacterial contamination of intraoperative salvaged
      blood producted by autologous transfusions device (CS; CELL SAVER 5, Heamonetics
      Corp., Braintree, MA). Eleven patients undergone open heart surgeries including 2
      emergency operations with a median sternotomy enrolled in this study. Blood
      samples were drawn from salvaged blood bags. Airborne contaminants (AB) were
      collected by a blood agar plate put besides the operation bed for 30 minutes. The
      median wounds samples were collected by a swab. Bacterial growth was detected in
      81.8% of salvaged blood samples. Twenty-nine bacterium were isolated from CS,
      72.4% of those were Staphylococci. 9.1% of sample was positive in wound swabs.
      Forty bacterium were isolated from plate cultures. 65% of them were
      Staphylococci. Staphylococcus epidermidis and coagulase negative Staphylococcus
      isolated both CS and AB in the 2 cases had the same identify codes, and incubated
      from several AB cultures. Corynebacterium sp. is also isolated from both CS and
      AB cultures in other 2 same cases. In 7 out of 8 cases (87.5%), from which
      Staphylococci isolated in CS, the Staphylococci were cultured from AB in not the
      same but the other cases. In conclusion, highly incidence of the identification
      in identical code of Staphylococci indicated that the main source of CS
      contamination was highly suspected to AB.

PMID- 11517545
TI  - [High pressure occlusion of leukocyte depletion arterial line filter in patients
      with cardio-pulmonary bypass surgery].
AB  - Cardio-pulmonary bypass (CPB) leads the activation of neutrophil, which may cause
      reperfusion organ dysfunction. Utility of using the leukocyte depletion arterial
      filter to pretend postoperative complications has been reported. The other side,
      the risk of the leukocyte depletion filter occlusion with high-pressures of CPB
      arterial line (high-pressure occlusion) has been noted. We used the leukocyte
      deletion filter (LG-6, Pall), and experienced two cases of high-pressure
      occlusion in 421 CPB surgery with LG-6 (0.48%). No high-pressure occlusion was
      occurred with 1,508 patients used the standard arterial line filter in it period
      (0%, p = 0.007). In the both cases of high-pressure occlusion, monitored arterial
      line pressure increased to over 340 mmHg within 10 minutes after CPB
      installation. The filters were changed to standard type, then no more filter
      trouble was occurred. In the second case, we inspected the occluded LG-6. Light
      microscopic survey showed eosin stained small spherical cells (HE) and negative
      for fibrin (PTAH). Electromicroscopy revealed that spherical cells (1-2 microns)
      adherated to structure of the filter. No fibrin was detected with Gel
      electrophoresis. Because of the pathologic analysis, the cells, which might cause
      the filter occlusion, were platelet. In addition, no fibrin exist suggests that
      the coagulation system did not relate to the high-pressure occlusion. In
      conclusion, we experienced two high-pressure occlusion cases of the leukocyte
      depletion arterial filter with CPB surgery (0.48%); the filter occlusion may be
      caused by the initial thrombus formation by platelet.

PMID- 11517546
TI  - [Early and mid-term results of elephant trunk method using stent graft during
      total arch replacement].
AB  - Combined therapy of stent graft implantation and open surgery is an alternative
      method for aortic aneurysm. Seven patients with aortic aneurysm [annulo aortic
      ectasia (AAE) + Marfan syndrome (4), AAE + arch aneurysm + s/o Behcet disease
      (1), acute dissected aneurysm (type A) (1), thoracic aortic true aneurysm (1)]
      were successfully treated by means of elephant trunk method using a stent graft
      during total arch replacement. There was no complication related to the stent
      graft during the perioperative period. Postoperative computed tomographic scans
      were performed 1 and 6 months later. There was no endleak and no migration, and
      the aortic diameter around the stent graft was not changed in six patients.
      However, one patient showed thrombus around the stent graft, because of endleak 2
      months after the operation. Such patients should therefore have careful long-term
      follow-up.

PMID- 11517547
TI  - [A clinical study of resected bronchopulmonary carcinoids].
AB  - 19 surgically treated cases with bronchopulmonary carcinoid in our hospital were
      studied clinically, and we discussed the criteria of limited operation for
      typical carcinoid. 11 cases had typical carcinoid and 8 had atypical. All
      patients of typical type were alive with no recurrence. No lymph node metastasis
      was revealed in all cases of typical type. On the contrary, in cases of atypical
      type, 1 had n 2 disease and 1 had distant metastasis. The five survival rates of
      patients with typical carcinoid was 100%, and significantly better than that of
      patients with atypical, 27%. Therefore, patients with typical carcinoid can be
      cured by limited operation, but radical operation should be indicated for
      atypical carcinoid.

PMID- 11517548
TI  - [Anti-bleeding effect of nafamostat mesilate for the surgery of thoracic
      ascending aorta].
AB  - During extracorporeal cardiopulmonary bypass (ECB), the activated coagulation and
      fibrinogenolysis system causes bleeding and postoperative multiple organ
      failures. We studied the effect of an anti-bleeding agent, nafamostat mesilate
      (NM) during the surgery of thoracic ascending aorta to decrease a side effect of
      bleeding. From March 1980 to January 1998, for thoracic ascending aorta
      operations in our department (true aneurysm, 16-, psudoaneurysm, 2-, and
      dissection, 11 cases, in 29 cases, respectively), age from 16 to 79 (mean 62.9 +/
      9.5 year of age), we classified the objects in two groups, NM group
      (intraoperative infusion with NM of 60 mg/hr and with heparin 300 IU/kg) and C
      group (only with heparin treated, 500 IU/kg). We investigated the preoperative
      factors (age and aneurysmal diameter), the intraoperative factors (ACT,
      hematcrit, platelet, aorta clamping time, operative time, ECB time, bleeding
      volume, and blood transfusion), and the postoperative factors (bleeding and blood
      transfusion) after the administration of NM. RESULTS: There was no significance
      for the protection effect of NM infusion on the preoperative and the
      postoperative factors. However, intraoperative bleeding and blood transfusion
      volume in NM group were significantly lesser than those in group C. CONCLUSIONS:
      It might be useful for NM infusion during the surgery of thoracic ascending aorta
      due to the decrease of volume of intraoperative bleeding and blood transfusion
      amount with the remarkable anti-bleeding effect.

PMID- 11517549
TI  - [Surgical treatment of infectious endocarditis complicated by discrete subaortic
      stenosis: report of a case].
AB  - A 39-year-old male with a history of cardiac murmur from early childhood was
      diagnosed as having infectious endocarditis (IE) complicated by discrete
      subaortic stenosis (DSS). Echocardiography revealed severe aortic regurgitation,
      subaortic membranous structure and mild mitral regurgitation. The pressure
      gradient across the subaortic stenosis was 105 mmHg according to continuous
      Doppler wave ultrasonography. Aortic valve replacement and resection of subaortic
      membranous tissue and mitral annuloplasty were performed. Postoperative cardiac
      catheterization demonstrated that the hemodynamic data were remarkably improved,
      and the patient was free of symptoms. He is currently well at 6 months after the
      operation.

PMID- 11517550
TI  - [A coronary artery bypass grafting using cardiopulmonary bypass with intraaortic
      balloon pumping in patient with low cardiac function combined with cerebral
      vascular disease].
AB  - We reported a 55-year-old man, who had coronary and cerebral vascular disease.
      Cerebral angiography showed occlusion at left internal carotid artery (ICA) and
      50% stenosis at right ICA C4 portion. But acetazolamide reactivity was kept
      symmetrically. Coronary angiography showed severe three vessel disease, and left
      ventriculography showed diffuse severe hypokinesis/akinesis, and EF was below
      30%. The patient underwent coronary artery bypass grafting using cardiopulmonary
      bypass with intraaortic balloon pumping to keep intraoperative blood pressure
      high. After the operation he recovered uneventfully without neurological
      complication.

PMID- 11517551
TI  - [Recurrent angina due to high grade re-stenosis of the left subclavian artery
      after coronary artery bypass grafting in a patient on hemodialysis for chronic
      renal failure: report of a case].
AB  - A 49-year-old woman on hemodialysis for chronic renal failure was admitted to our
      hospital with chest pain. She had undergone quadruple coronary artery bypass
      grafting (CABG) including a left internal thoracic to left anterior descending
      coronary artery anastomosis 9 months earlier. The blood flow through the left
      internal thoracic artery had decreased due to high grade stenosis at the proximal
      portion of the left subclavian artery, and recurrent angina had developed. She
      was treated by the placement of Palmaz biliary stents in the left subclavian
      artery, but re-stenosis occurred after 9 months, causing recurrent angina again.
      There fore, an operation was proposed and bypass grafting from the descending
      aorta to the left subclavian artery was successfully performed, resulting in
      complete resolution of her recurrent angina. This case serves to reinforce that
      patients on dialysis must be carefully followed up after CABG.

PMID- 11517552
TI  - [Edge to edge repair for mitral regurgitation in a patient with chronic
      hemodialysis: report of a case].
AB  - In a patient with chronic hemodialysis, the high risk of calcific degeneration of
      biological prosthetic valve and anticoagulant related complications after valve
      replacement have been reported. A 71-year-old woman with hemodialysis underwent
      the edge to edge repair combined with ring-annuloplasty for mitral regurgitation
      caused by the anterior leaflet prolapse without any torn chordae. Postoperative
      course was uneventful. There was no significant mitral regurgitation. Double
      mitral orifices were confirmed by the postoperative echocardiography. A
      calculated functional mitral valve area was 3.06 cm2. The edge to edge repair is
      a simplified technique and carried out in a short time. We believe the edge to
      edge repair is a useful technique for anterior mitral valve prolapse in a patient
      with chronic hemodialysis.

PMID- 11517553
TI  - [Intravenous leiomyomatosis with cardiac extension in an elderly woman: report of
      a case].
AB  - Intravenous leiomyomatosis is a histologically benign smooth-muscle tumor arising
      from either a uterine myoma or the wall of a uterine vessel with extension into
      veins. We describe a 71-year-old woman with a prior history of subtotal
      hysterectomy for uterine myoma years earlier who presented with palpitation.
      Echocardiographic examination revealed an intracardiac mass protruding into the
      right ventricle during diastole. The caval tumor could be traced to the right
      renal vein by magnetic resonance image. She was operated on for intracardiac and
      intracaval leiomyomatosis. The intracaval tumor proved to be not totally
      resectable. Presence of smooth muscle was confirmed by smooth muscle actin and
      desmin positive cells in the tumor. Tumor cells also proved to possess estrogen
      receptors. The patient has been closely followed-up with antiestrogen therapy.

PMID- 11517554
TI  - [Staged operation for right isomerism with total anomalous pulmonary venous
      return: report of a case].
AB  - A male infant with right isomerism, single ventricle, severe pulmonary stenosis
      (PS), and total anomalous pulmonary venous return (TAPVR) underwent successful
      staged Fontan operation. Pulmonary vein drained into right superior vena cava
      without a stenotic lesion. Common pulmonary venous chamber was also connected
      with the atrium by a thin bridging vein. Blalock-Taussig shunt was performed at 2
      month-old. Because of progressive pulmonary congestion, an anastomosis between
      common pulmonary venous chamber and the atrium followed 4 days after the first
      shunt. Bidirectional cavopulmonary shunt was performed 7 months after the second
      operation. Because of progressive atrioventricular valve regurgitation, repeated
      bandings of the shunt were required to regulate the pulmonary flow. Total
      cavopulmonary connection was completed 9 months after the BCPS. Staged operation
      is a useful strategy to acquire an appropriate pulmonary blood flow for the
      isomeric heart with TAPVR and severe PS.

PMID- 11517555
TI  - [A case of mucosa associated lymphoid tissue (MALT) lymphoma].
AB  - We examined a 49-year-old man, who was referred to our hospital for resection of
      abnormal findings on the X-ray. Before hospital admission, he was performed TBLB
      and aspiration biopsy in other hospital, but the results was not decided
      diagnosis. Because the possibility of the lung cancer was not completely nagated,
      we performed the tumor resection (partial pulmonary resection) in use of
      thoracoscopy. The tumor was diagnosed as a MALT (mucosa associated lymphoid
      tissue) lymphoma at histologically and immunohistologically (CD 79), and
      resectable lymph node did not detected malignant cell. He has had no evidence of
      recurrence for 5 months after the operation.

PMID- 11517556
TI  - [A surgically treated case of capsulated thymoma with thymic cyst].
AB  - A 56-year-old woman was pointed out an abnormal shadow on chest roentgenogram.
      Chest CT and MRI showed a solid mass with a cyst at right anterior mediastinum.
      Clinical diagnosis was thymoma with cyst, and surgical excision was performed.
      The histopathological examination of the resected specimen demonstrated that the
      epithelia of the cyst wall was single cuboidal or squamous cells and contained
      some foci of thymic tissue. The solid mass was capsulated and predominantly
      composed of lymphocytes. The pathological diagnosis was a thymoma (predominantly
      lymphocytic type) with thymic cyst. She is doing well for 10 years
      postoperatively.

PMID- 11517557
TI  - [A case of mediastinal esophago-bronchogenic cyst associated with high serum
      level of CA 19-9].
AB  - We report a case of mediastinal esophago-bronchogenic cyst in a patient with a
      high serum level of CA 19-9. A 49-year-old man presented with a complaint of
      dysphagia. Chest X-ray, CT, and MRI showed posterior mediastinal cystic shadow
      which was diagnosed preoperatively. The serum level of CA 19-9 was 158 U/ml. We
      underwent extirpation of the cyst through video-assisted thoracoscopic surgery
      (VATS) and confirmed to be a bronchogenic cyst histologically. The serum level of
      CA 19-9 returned to normal after the operation.

PMID- 11517558
TI  - [A successful surgical case of incomplete atrioventricular septal defect with
      pulmonary dysfunction].
AB  - A 58-year-old female with incomplete atrioventricular septal defect was treated
      successfully with surgery. We repaired the defect by closure of atrioventricular
      septal defect, suture of cleft and tricuspid valve annuloplasty. We adopted
      method of minimally invasive cardiac surgery (MICS) expecting to preserve
      pulmonary function and to perform tracheostomy on early stage. After the
      operation she recovered with no major complications. It is suggested that MICS is
      effective method for patients with pulmonary dysfunction.

PMID- 11517559
TI  - [The alternative or simultaneous excretion of different species of mycobacteria
      in atypical mycobacteriosis--15 cases in 7 years].
AB  - Five hundreds and five cases of Mycobacterium tuberculosis infection admitted to
      our hospital during 7 years from 1993 to 1999. Numbers of newly diagnosed cases
      were 390, of which 329 (84.4%) were bacilli positive with sputum examination on
      admission. The recurrent cases were 115, of which 55 (47.8%) were bacilli
      positive cases. During the same period, mycobacteria other than tuberculosis
      (atypical mycobacteria) were detected in the sputum of other 121 cases. The 63
      (52.1%) out of these 121 cases were diagnosed as atypical mycobacteriosis (AM)
      due to repetitive detection of bacilli with fulfilled the criteria according to
      the Japanese Mycobacteriosis Research Group of the National Chest Hospitals. The
      ratio of 63 AM cases to 329 bacilli positive TB cases was 19.1%, but it range
      from 8.2% to 31.3% year by year. In these 63 AM cases, 9 (14.3%) cases excreted
      AM bacilli simultaneously or alternately with TB bacilli. The other 15 (23.8%)
      cases excreted different AM bacilli simultaneously or alternately. The changes or
      combinations with M. avium and M. intracellulare were most frequently observed
      (in 12 cases). The manners of changes and combinations with different species
      were described in detail.

PMID- 11517560
TI  - [Pulmonary Mycobacterium Kansasii infection in the southern area of Fukuoka
      prefecture].
AB  - Cases of pulmonary infection caused by Mycobacterium kansasii (Mk) in our
      hospital located at the mid-northern area of the Kyushu district, which is in the
      southern part of Fukuoka prefecture were evaluated. Mk infection is not so rare
      in other areas of Japan, such as Tokyo and Kinki district, however, there has
      been no published report on the disease from the Kyusyu district. Therefore, the
      frequency and the clinical features of our cases of Mk infection were analyzed.
      During 17 years from 1982 to 1998, there were 14 patients of Mk infection out of
      241 nontuberculous mycobacteriosis (NTM). There were 595 patients of culture
      positive pulmonary tuberculosis without prior treatment (Tbc). The proportion of
      Mk/Tbc was 2.4% and that of Mk/NTM was 5.8%. During the period A (from 1982 to
      1994) the ratio of Mk/Tbc was 5/462 (1.1%), while on the other side that of
      Mk/Tbc during the period B (from 1995 to 1998), it was 9/133 (6.8%), which was
      significantly (P < 0.01) higher compared with that in the period A. Although the
      patients of Mk infection in our hospital had been rare until 1994, from the
      results mentioned above, it was considered that the frequency of Mk infection in
      our hospital has increased to some extent since 1995. One of the characteristics
      in our cases was that the ratio of female (42.9%) was relatively high. All the
      female patients were considered to be compromised hosts. The results of the drug
      resistance tests were consistent with the other reports in our country. By the
      combination treatment including rifampicin as the major drug, the negative
      conversion of culture were obtained within 2 months in all our cases.

PMID- 11517561
TI  - [Tuberculosis of the elderly (above the age of 75) in national hospitals].
AB  - In Japan tuberculosis is becoming rapidly the disease of the elderly. We studied
      the background, the type and level of hospital cares needed, and the outcome of
      patients with pulmonary tuberculosis (sputum smear and/or culture positive) above
      the age of 75 who were admitted to 8 national hospitals during the period from
      January 1 to December 31, 1997. The study included 150 patients (male: 109,
      female: 41, mean age: 81.6), of whom 25% needed care in a single-bed room, 84.3%
      had underlying diseases (cardiovascular diseases: 43.3%, malignant diseases:
      20.9%, neuro-psychiatric diseases: 13.4%), and 47.6% needed cares mainly in
      feeding and excretions. 92 patients (62.6%) improved and 45 patients (30.6%)
      died, of whom the cause of death was directly related to tuberculosis in 42. The
      mean hospital stay was 4.7 months. However, in 42 patients whose cause of death
      was related to tuberculosis, 66% died within 3 months, while in 102 patients who
      were discharged 71% stayed more than 3 months. The same comparison was done in
      508 patients with bacteriologically proven tuberculosis above the age of 75
      admitted to National Tokyo Hospital during the period from 1990 to 1999. The
      result was almost the same, among 133 patients died in the hospital 60% died
      within 3 months, while in 375 patients who were discharged hospital stay was more
      than 3 months in 70%. In the near future, the elderly will occupy more than 25%
      of the beds of the tuberculosis ward in Japan and most of them have underlying
      diseases other than tuberculosis. Because tuberculosis, once the disease of the
      young, is becoming rapidly the disease of the elderly, it is imperative for us to
      make necessary adjustments to meet this inevitable trend.

PMID- 11517562
TI  - [Cat scratch disease showing clinical picture resembling tuberculous
      lymphadenitis: a case report].
AB  - On February 18th, 1997, a 61-year-old woman visited our hospital because of a
      left inguinal mass. On physical examination, the mass was soft without
      inflammatory sign. About one month later, the node was excised. Pathological
      examination revealed granulomas with caseous necrosis and Langhans giant cells,
      suggesting tuberculosis, although acid fast stain was negative. Thereafter, re
      history taking in detail disclosed that a kitten had often scratched her. We
      reexamined the pathology and checked her for serum antibodies to Bartonella
      henselae, the etiological microbe of cat scratch disease (CSD), using enzyme
      immunoassay. Histopathological reexamination of the excised mass revealed
      suppurative granulomas in addition to caseous ones. The level of IgG (negative: <
      12 units) to B. henselae was 78 units on March 25th, 138 units on April 19th, and
      18 units on July 18th, while the level of IgM (negative: < 12 units) was negative
      at each determination. These serological results strongly suggested current
      infection of B. henselae. The diagnosis of CSD could be established based on the
      history and the laboratory findings. When one encounters a case of granulomatous
      lymphadenitis, CSD should be considered for the differential diagnosis, and in
      this regard, anamnesis about contact with cats should be asked.

PMID- 11517563
TI  - [Tuberculosis control strategy in the 21st century in Japan--for elimination of
      tuberculosis in Japan].
AB  - Modern tuberculosis control programme has been launched in 1951 by the major
      revision of the previous Tb. Control Law in Japan. Main control measures were BCG
      vaccination programme for tuberculin negatives, annual screening of Tb. by
      miniature radiophotography (MMR), charge free diagnosis and treatment of Tb.
      patients, registration and case-holding at Health Centres throughout the country
      and so on. Thanks to the efforts of the Government and people concerned, Tb.
      incidence has decreased with the annual reduction rate of 11% during 1961 and
      1977. However, Tb. decrease has stagnated after that, and it is increasing slowly
      in these 3 years since 1998. Moreover, regional variations of Tb. incidence are
      considerable, and Tb. is concentrated in specific risk groups such as elderly
      persons, homeless, foreign born individuals and so on. However, the present Tb.
      Control measures were introduced prior to the discovery of most major anti-Tb.
      drugs and all modern internationally accepted Tb. Control strategies, so that it
      is strongly desired to improve the present control programme from rather
      classical present Tb. control measures to global standard one to overcome the
      resurgence of Tb. in Japan. At first, the author stressed that the priority of
      Tb. Control Programme should be changed according to the development of science
      and the change of epidemiological situations. BCG vaccination and Tb. screening
      by MMR might be very important when the annual risk of Tb. infection was very
      high--about 4% in 1950. Now it is around 0.05% and the incidence of Tb. among 0
      14 years of age is 1.1 per 100,000 so that the priority should be given on
      treatment of the detected cases instead of BCG vaccination or MMR. The doctors in
      the public health field should give more strong concern on clinical aspects of
      Tb. Control Programme at present. It was considered that the main urgent problems
      to be improved in the present Tb. control measures are as follows. 1. It is
      strongly recommended to spread the global standard regimen with 2HRZE/4HR (E)
      more widely and rapidly. Because the standard regimen is used in only 50% of new
      smear positive cases at present although 15.3% of Tb. patients are 80 years or
      more, or 56.3% of them are 60 years or more, and the side effects by PZA are
      higher among elderly patients. 2. Shortening of the hospitalization duration is
      required because 76.7% of newly detected bacilli positive cases are hospitalized
      at first, and the median of the period of hospitalization is 4 months, and 18.4%
      of them are hospitalized 6 months or more at present. 3. DOT treatment has been
      introduced for special groups in the big cities in 2000 for the first time in
      Japan, but it is needed to spread DOT treatment more widely, for example, by
      increasing health insurance payment for the institutions where DOT treatment is
      being implemented. 4. It is recommended to build special rooms to accept Tb.
      patient at general hospitals and/or university hospitals to avoid the neglect of
      Tb. by general medical doctors. 5. Follow-up of Tb. patients after treatment
      completion at Health Centres is not needed now, because the relapse rate is so
      low. 6. Indiscriminative screening programme for all the people aged 19 years old
      or more should be stopped, at least up to 39 years of age, because Tb. detection
      rate has become so low as 0.0069% at present. As Tb. decrease is so slow, or is
      increasing in some areas, that the contact surveys among the young aged 20 to 39
      should be strengthened in the future. 7. As Japan Anti-Tb. Association is being
      carrying out mass screening programme extensively at present, so that the
      Association has started to discuss the future health check system. Because of the
      rapid and constant increase of the lung cancer, the Association is discussing the
      method to detect the lung cancer, too. In any way, it is needed to focus the
      screening programme for special high risk groups instead of indiscriminative
      screening. 8. BCG vaccination for infants should be continued a little more,
      because BCG vaccination can protect the development of 7 miliary Tb. and/or
      meningitis cases during 15 years if BCG is given 70% of the infants in 2000.
      However, it was strongly recommended to stop re-vaccination of BCG, because it is
      not so effective, and disturb the diagnosis of Tb. infection by tuberculin
      testing. 9. Treatment of latent Tb. infection will become more and more
      important, so that it's indication should be expanded to the adults in the future
      instead of the present indication up to 29 years of age. It is needed to revise
      Tuberculosis Control Low to improve control programme in Japan. The author hoped
      that the members of Japan Tuberculosis Society will promote the improvement and
      to support the Government to improve the Law.

PMID- 11517564
TI  - [Immunohistochemical analysis with anti-cytokeratin antibody in the prostatic
      epithelium].
AB  - PURPOSE: We performed immunohistochemical studies of the prostatic epithelium
      using three different anti-cytokeratin monoclonal antibodies (35 beta-H11,
      RCK108, and 34 beta-E12), and also investigated the immunoreactivity of various
      prostatic lesions with basal cell specific anti-cytokeratin antibody (34 beta
      E12). MATERIALS AND METHODS: One hundred and thirty one prostatic specimens were
      obtained at surgery or biopsy. H-E stained sections were available for review in
      all cases. They were classified according to histopathology; benign prostatic
      hyperplasia (BPH), prostatic cancer (PCA), atrophic acini, atypical adenomatous
      hyperplasia (AAH), and prostatic intraepithelial neoplasia (PIN). ABC or LSAB
      method was utilized for immunohistochemical staining with 3 anti-cytokeratin
      monoclonal antibodies. RESULTS: 35 beta-H11 was mainly stained in the luminal
      cells and RCK108 was stained both in the luminal and the basal cells in BPH. 35
      beta-H11 showed highly positive staining in the prostatic cancer regardless of
      degree of differentiation. RCK108 tended to be less stained in the prostatic
      cancer cells with lower grades of tumor differentiation compared to those with
      higher grades. 34 beta-E12 was stained only in the basal cells, but neither in
      the normal luminal cells nor the cancer cells. Using 34 beta-E 12, basal cells
      were positively stained in most of the cases with BPH, while not in PCA. Atrophic
      acini and AAH was stained with 34 beta-E12 as positively as BPH. Basal cells were
      discontinuously or negatively stained in many cases with high-grade PIN.
      CONCLUSIONS: The luminal cells in BPH were highly positively stained using 35
      beta-H11 or RCK108. RCK108 tended to be less stained in the prostatic cancer
      cells with lower grades of tumor differentiation. Positive staining of 34 beta
      E12 strongly suggested a benign lesion, therefore immunohistochemistry using this
      antibody would be useful as an aid for pathological diagnosis.

PMID- 11517565
TI  - [Laparoscopy-assisted total nephroureterectomy for renal pelvic and/or lower
      ureteral cancer].
AB  - PURPOSE: The usefulness of laparoscopy-assisted total nephroureterectomy for
      patients with renal pelvic and lower ureteral cancer is evaluated. MATERIAL:
      Seven patients with renal pelvic cancer and four with lower ureteral cancer
      performed laparoscopy-assisted total nephroureterectomy from May 1997 to December
      2000 (Ten males and one female, mean age 68.5 year-old). METHOD: Of the 11
      patients, the initial one received preoperative embolization of the renal artery.
      Under general anesthesia laparoscopy-assisted total nephroureterectomy underwent
      via transperitoneal approach in three patients and retroperitoneal approach in
      eight. After the kidney was completely dissected under laparoscopic procedure, it
      was delivered en bloc with ureter from the skin incision in the lower abdomen.
      RESULT: Two patients needed conversion to open surgery. The mean operating time
      of nine patients except for conversion cases was 272 minutes and the mean blood
      loss was 313 ml. There was no major complication associated with laparoscopic
      procedure. There was no significant difference in both complication and
      recurrence rate between laparoscopy-assisted total nephroureterectomy and open
      surgery. CONCLUSION: Laparoscopy-assisted total nephroureterectomy is an useful
      procedure for the treatment of patients with renal pelvic and lower ureteral
      cancer because it enables us to remove out the kidney and ureter from one small
      lower abdominal incision.

PMID- 11517566
TI  - [Development of new hydrophilic catheter kit for self-catheterization: study in
      pediatric cases].
AB  - PURPOSE: To increase the management of self-catheterization in children of school
      age, a catheter kit consisting of hydrophilic catheter and a packet containing
      sterilized water was developed. We evaluated the lubricating characteristic and
      clinical efficacy of this new catheter kit. MATERIALS AND METHODS: The catheter
      kit used in the study was a pocket-size plastic container in which a polyurethane
      catheter coated with hydrophilic polymer and a packet containing sterilized water
      were packed in combination. The lubricating characteristic of catheter was
      assessed by the measurement of friction value. For clinical assessment, male
      children aged over 6 years old who were doing self-catheterization at 17 medical
      institutions nationwide were selected as the subjects. The 32 children who had
      given informed consent (mean age: 11.6 years old) were asked to use the catheter
      kit continuously for 1 week. The results were investigated by a questionnaire
      survey in which the assessment before and after the use was expressed in scores.
      At the same time, urinalysis and urine culture were examined. RESULTS: The
      friction value of hydrophilic catheter was equivalent to or less than that
      observed by applying a lubricant to the conventional catheter. The comparison of
      conventional catheter with the kit indicated significantly higher scores
      (assessment in 5 grades expressed in scores) for the portability and operability
      of the kit. Though there was no significant difference in the ease of insertion
      between the two catheters, there were several comments that the kit got stuck in
      the urethra when it was withdrawn. The global assessment gave a significantly
      higher score to the kit and 30 (94%) of the 32 children wanted to use the kit
      continuously. No increase in hematuria which caused a clinical problem or no new
      apparent urinary tract infection occurred after the use of the kit. CONCLUSIONS:
      Compared with the conventional catheter, the hydrophilic catheter kit highly
      satisfied a large number of children at the time of self-catheterization.
      Depending on the condition of children, the kit is considered useful for
      continued self-catheterization for a long term.

PMID- 11517567
TI  - [High-dose rate Iridium-192 brachytherapy with flexible applicator--a trial
      toward decrease of stress during treatment and improvement of quality of life].
AB  - PURPOSE: We tried to improve the materials and methods of high-dose rate Iridium
      192 brachytherapy for localized prostate cancer and evaluated the stress during
      the treatment in 20 patients with whom the therapy was performed. MATERIALS AND
      METHODS: Rigid applicators made of stainless steel of 1.6 mm in diameter were
      indwelt with a template as usual for 30 hours in 14 patients (group A). Flexible
      applicators made of polyoxymethylene rosin (POM) of 2.0 mm in diameter were
      indwelt without a template for 30 hours after the applicator insertion in 6
      patients (group B). We made inquiries about lumbago, inconvenience and necessity
      of assistant help and sleep in the course of therapy, and urinary incontinence
      and erectile function after the course of therapy as the QOL. RESULTS: The stress
      during the course of therapy in the patients of group B was obviously less than
      that of group A. There were no significant differences in urinary incontinence
      and erectile function after the course of therapy between group A and B.
      CONCLUSION: In this study, our trial successfully reduced the stress during the
      course of therapy in the patients with localized prostate cancer in the course of
      high-dose rate Iridium-192 brachytherapy.

PMID- 11517568
TI  - [High-dose rate iridium-192 brachytherapy combined with external beam
      radiotherapy for localized prostate cancer].
AB  - PURPOSE: We report our technique and also preliminary results in the cases with
      localized prostate cancer treated by the combination of high-dose rate Iridium
      192 (HDR-Ir192) brachytherapy and external irradiation. MATERIALS AND METHODS:
      From June 1999 to August 2000, 17 patients were treated by the combination of HDR
      Ir 192 and external beam. The mean age of patients was 72 years (range, 48-81
      years). The clinical stage was B1 in 5, B2 in 7 and C (no cancer with seminal
      vesicle) in 5 cases. Of 10 patients without neoadjuvant hormonal therapy, the
      median initial pretreatment PSA was 15.3 ng/ml (6.93-222.32 ng/ml). The treatment
      was given by HDR-Ir 192 brachytherapy (6 Gy x 3 times/2 days) and external beam
      irradiation (40 or 45 Gy). The brachytherapy was given using TRUS guided
      percutaneously inserted temporary needles with a high dose rate remote
      afterloading control. Local control was evaluated by digital rectal examination.
      TRUS-guided biopsies and serum PSA evaluations. Follow-up ranged from 2 to 14
      months, with a median of 8 months. RESULTS: In 4 (40.0%) of 10 patients without
      neoadjuvant hormonal therapy the level of serum PSA was decreased to less than
      4.0 ng/ml within 3 months after the therapy. The effective grade in the biopsy
      specimens of 8 patients without neoadjuvant hormonal therapy was Grade Ob in 4,
      Grade 1 in 1, Grade 3 in 3 cases at 3 months after the therapy. No severe intra-
      or peri-operative complications occurred. CONCLUSION: The combined radiotherapy
      treatment is safe and effective for use in the patients with localized prostate
      cancer. However, more comprehensive studies involving long-term follow-up and
      great numbers of the cases with localized prostate cancer treated by the
      combination of HDR-Ir 192 brachytherapy and external irradiation will be
      necessary to determine whether this therapy contributes to better prognosis.

PMID- 11517569
TI  - [Systemic lupus erythematosus presenting as a brainstem infarction and hemorrhage
      during treating retroperitoneal abscess: a case report].
AB  - We report a case of a brainstem infarction and hemorrhage seen in a 21-year-old
      female with systemic lupus erythematosus (SLE) during treating retroperitoneal
      abscess. SLE has been treated with prednisolone and mizoribine for 4 years. The
      patient with right back and lower abdominal pain visited our hospital. Computed
      tomography (CT) revealed retroperitoneal abscess over surrounding right kidney,
      horizontal part of duodenum and in front of psoas muscle. Drainage was done with
      indwelled right single J catheter and penrose drain. Retroperitoneal abscess was
      much smaller, but, post drainage day 17, high fever, unconsciousness, down-blood
      pressure and down-beat nystagmus appeared suddenly. Brain CT scan revealed a
      brainstem wide infarction and hemorrhage spot. Pulse therapy with steroid was
      done, however unfortunately the patient was dead after 6 days.

PMID- 11517571
TI  - [Bowel perforation after extracorporeal shock wave lithotripsy: a case report].
AB  - A case of intestinal perforation caused by ESWL for left ureteral calculus is
      reported. A 69-year-old male underwent the graft replacement for bilateral iliac
      aneurysm in March, 1996. In February, 1999, there appeared left flank pain, and a
      diagnosis of left ureterolithiasis was made by radiological examination. On March
      29 he was admitted to our department for ESWL. On March 30, ESWL for calculus in
      the pelvic region was performed with the patient in the prone position. The
      patient complained of the left lower abdominal pain immediately after ESWL, but
      no muscular defense was observed. Since the pain was not relieved, CT was
      performed on March 31, but no evident abnormal finding was found. Thereafter the
      pain continued and on April 2 muscular defense was also noted. On CT performed a
      second time, free air and evidence of ileus were found, so emergency operation
      was performed. Two perforations about 2 mm in size were found in the jejunum 130
      cm from the Treitz' ligament, which led to diagnosis of intestinal perforation
      due to ESWL. The patient followed a satisfactory postoperative course and was
      discharged on April 23. There has been only one reported case of intestinal
      perforation due to ESWL. It is a very rare complication. However, this
      complication should be taken into consideration where the patient has the history
      of abdominal surgery and where ESWL was performed with the patient in the prone
      position.

PMID- 11517572
TI  - [Inflammatory pseudotumor of the kidney: report of a case].
AB  - We report a case of inflammatory pseudotumor of the kidney. A 73-year-old man
      presenting with general malaise and minimal grade fever visited a medical
      department in our hospital. Computerized tomography incidentally revealed a
      tumor, 3.5 cm in diameter, in the lower pole of the left kidney, and he was
      referred to our outpatient department. Selective left renal arteriography
      disclosed an avascular mass on the affected site. Left radical nephrectomy was
      performed under the diagnosis of avascular renal cell carcinoma. Histological
      examination demonstrated a tumor composed of spindle-shaped fibroblastic cells
      infiltrated by variable numbers of plasma cells, small lymphocytes and
      histiocytes. The pathologic diagnosis was renal inflammatory pseudotumor.
      Fourteen previously reported cases of this tumor have reviewed in the literature.

PMID- 11517570
TI  - [A case of hypothyroidism induced by interferon therapy for renal cell
      carcinoma].
AB  - A 54-year-old man, who had undergone left radical nephrectomy due to a renal cell
      carcinoma 2 years previously, had received adjuvant interferon (IFN) therapy for
      2 years. One month has passed after IFN therapy, when he started to complain of
      muscle pain. The serum FT3 and FT4 levels were lower than normal range. We
      diagnosed for hypothyroidism induced by IFN therapy, and he was treated with
      thyroxine. His serum FT3 and FT4 levels were increased after the initiation of
      the thyroxine therapy. Many reports of hypothyroidism induced by IFN therapy have
      been found during the treatment for chronic hepatitis. The hypothyroidism induced
      after IFN therapy of renal cell carcinoma is very rare. It should be brought to
      attention that IFN therapy induces hypothyroidism not only during treatment
      period, but also after the treatment. Careful examination after the therapy is
      mandatory.

PMID- 11517573
TI  - [Low dose CVD chemotherapy as a tumor dormancy therapy for extra-adrenal
      malignant pheochromocytoma: a case report].
AB  - A 38 year-old man presented with upper abdominal mass and hypertension pointed
      out at a medical examination. Blood pressure was 170/90 under medication of an
      alpha-blocker. Abdominal CT scan showed an 8 x 8 cm inter-aortocaval mass
      displacing pancreas head ventrally, and further a 4 x 4 cm mass at the aortic
      bifurcation, but there was no tumorous lesion in bilateral adrenal glands. Plasma
      nor-epinephrine level and urinary VMA excretion were excessive but plasma
      adrenaline level was within normal limits. MIBG scintigram showed hot spots in
      the 4th and 9th thoracic vertebrae. The destructive change of the 9th vertebra on
      magnetic resonance imaging strongly suggested metastasis of the tumor. Histologic
      and immunohistochemical findings of the biopsy specimen taken from the lower
      abdominal tumor in addition to the above clinical data led to the diagnosis of
      extra-adrenal malignant pheochromocytoma with spinal metastases. Since 2 cycles
      of full dose CYVADIC chemotherapy had no effects on lowering the high blood
      pressure and reducing the tumor size, low dose (60% of the full dose) CVD
      (cyclophosphamide, vincristine and dacarbazine) was given as a palliative
      chemotherapy on an out-patient clinic approximately every 4 weeks. After 4 cycles
      of the chemotherapy, his backache due to spinal metastasis markedly improved,
      hypertension as well as the plasma dopamine level was normalized and nor
      epinephrine level was markedly decreased, though the tumor size was not reduced.
      Thereafter, no medication for hypertension was necessary. During 3 years and 6
      months until now, 36 cycles of the chemotherapy has been repeated with no
      significant side effects. He has been at full-time work with quality of life
      being well preserved. Low dose CVD regimen appears to be an effective tumor
      dormancy therapy for advanced extra-adrenal pheochromocytoma.

PMID- 11517574
TI  - Completion pneumonectomy for recurrent or second primary lung cancer.
AB  - OBJECTIVE: We studied 8 patients undergoing completion pneumonectomy for
      recurrent or second primary lung cancer. METHODS: Subjects were men who averaged
      62 years of age. Of these 6 had p-stage I, and 2 p-stage II disease at initial
      operation. At the second operation, we diagnosed 3 with second primary lung
      cancer and 5 with recurrent lung cancer. We predicted postoperative pulmonary
      function by calculating the predicted forced expiratory volume in 1.0 second
      (FEV1.0) from residual numbers of subsegments after completion pneumonectomy. All
      predicted FEV1.0 in our 8 cases ranged from 544 to 926 (773 +/- 144) ml/m2.
      RESULTS: Six patients experienced postoperative complications and morbidity was
      75%. One patient undergoing completion sleeve pneumonectomy after radiation
      therapy for local carina recurrence died on 7th postoperative day due to
      anastomotic dehiscence and pneumonia. Overall operative mortality was 12.5%
      (1/8). Four remain alive and actuarial 5-year survival was 37.5%. CONCLUSIONS:
      Careful consideration is needed in determining operative indications for
      completion pneumonectomy for patients after radiation therapy. Patients with
      recurrent squamous cell carcinoma who have p-stage I disease at initial operation
      and those with second primary lung cancer and p-stage I or II disease can expect
      relatively a long-term survival, and we concluded that completion pneumonectomy
      could be conducted in these cases with a satisfactory prognosis.

PMID- 11517575
TI  - Experimental study of pulmonary artery infusion with cisplatin in a solitary
      pulmonary tumor model using a rat colorectal adenocarcinoma cell line.
AB  - OBJECTIVES: We assessed a tumor model prepared by open lung injection to study
      metastatic lung tumors, and evaluated the efficacy of pulmonary artery infusion.
      METHODS: Subjects were 30 male F344 rats. In experiment 1, we evaluated
      chemosensitivity of a rat colorectal adenocarcinoma cell line (RCN-9) using a
      colorimetric [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide]
      assay. In experiment 2, we injected RCN-9 cells into the left lung on day 0; on
      day 10, we measured tumor tissue blood flow before and after pulmonary arterial
      occlusion. In experiment 3, we injected RCN-9 cells into the left lung and
      conducted no further procedures in controls. The pulmonary artery infusion group
      underwent pulmonary artery infusion with 0.1 mg of cisplatin on day 3 and the
      sham group injection with saline solution alone. On day 10, rats were sacrificed
      and maximum tumor cross-section measured. RESULTS: In experiment 1, the drug
      concentration required to inhibit cell growth 50% was 2.45 x 10(-6) M. In
      experiment 2, tumor tissue blood flow decreased significantly after arterial
      occlusion (p = 0.003). In experiment 3, the maximum tumor cross-section in the
      pulmonary artery infusion group was significantly smaller than in shams (p =
      0.0027) and controls (p = 0.0019). CONCLUSIONS: The pulmonary artery supplies
      tumors with blood, so this model appears useful in studying metastatic lung
      tumors, whose size was reduced significantly by pulmonary artery infusion with
      cisplatin. Pulmonary artery infusion is thus a promising modality in metastatic
      lung tumor treatment.

PMID- 11517576
TI  - Early results and characteristic problems associated with cardiac surgery in long
      term dialysis patients.
AB  - OBJECTIVE(S): To analyze early results and characteristic problems that develop
      after cardiac surgery on dialysis patients. METHODS: One hundred fourteen
      patients on maintenance dialysis underwent cardiac surgery. Their mean age was
      63.5 +/- 9.7 years, and 87 (76%) were male. The causes of chronic renal failure
      were diabetes mellitus in 41 (36%) and chronic glomerulonephritis in 40 (35%).
      Patients had previously been on dialysis for a mean duration of 7.8 +/- 5.6 years
      (range; 0.25-24 years). RESULTS: Fourteen (12%) were emergent cases. Eighty six
      patients (75%) received isolated coronary artery bypass grafting (CABG), and 10
      patients underwent operations in which CABG was combined with other cardiac
      procedures. Twelve patients (14%) of the isolated CABG patient group (86
      patients) were restricted to non-clamping bypass procedure due to severe
      calcification of the ascending aorta. Calcification score, which was represented
      by the sum of all involved coronary artery segments, was also significantly
      higher in dialysis patients than in the control group (4.5 +/- 2.4 segments vs.
      1.5 +/- 2.1 segments, p < 0.05). Hospital mortality was 8.8% (10/114) overall,
      and 7% (6/86) in isolated CABG patients. The causes of deaths were as follows:
      intestinal necrosis in 3, arrhythmia in 2, cerebral infarction in 1, low output
      syndrome in 1, and sepsis in 3 (mediastinitis, pneumonia, and prosthetic valve
      infection). CONCLUSIONS: Long-term dialysis is a major risk factor in cardiac
      surgery. However, because the surgical results proved to be acceptable, long-term
      dialysis patients should not be denied cardiac surgery.

PMID- 11517577
TI  - Detection and management of concomitant coronary artery disease in patients
      undergoing thoracic aortic surgery.
AB  - OBJECTIVES: No method has been established to detect and manage coronary artery
      disease in patients undergoing thoracic aortic surgery. METHODS: Subjects were
      192 patients scheduled for elective thoracic aortic surgery. Selection criteria
      for coronary angiography included a history of coronary artery disease or a
      positive dipyridamole myocardial perfusion imaging test. RESULTS: Four patients
      were inoperable due to complications associated with coronary angiography or
      aneurysm rupture following coronary revascularization. A total of 55 patients
      with coronary angiography (group A) underwent 57 thoracic aortic operations and
      133 patients without coronary angiography (group B) underwent 143 similar
      operations. Of 13 group A patients with significant coronary stenosis, 9
      underwent either preoperative percutaneous transluminal coronary angioplasty (n =
      3) or concomitant coronary artery bypass (n = 6). Perioperative myocardial
      infarction occurred in 3 group A patients (5%) and in 4 group B patients (1%,
      ns). The incidence of cardiac events--perioperative myocardial infarction or
      cardiac death--in group A (11%, 6/57) was higher than that in group B (3%, 4/143;
      p < 0.05). Multivariate analysis demonstrated incomplete revascularization of
      major coronary arteries with significant stenosis as a risk factor for cardiac
      events (p = 0.0106). CONCLUSIONS: Although dipyridamole myocardial perfusion
      imaging was useful, additional selection criteria for coronary angiography is
      needed. Complete revascularization of major coronary arteries with significant
      stenosis is essential to reduce postoperative cardiac events.

PMID- 11517578
TI  - Ultrasonic integrated backscatter in early assessment of myocardial injury during
      open heart surgery.
AB  - OBJECTIVES: The recovery of cyclic variation of ultrasonic integrated backscatter
      in myocardial ischemia provides early assessment of myocardial injury and is
      useful in assessing myocardial injury during open heart surgery. METHODS: We
      studied 25 patients with valvular disease undergoing cardiac surgery--7 with
      aortic stenosis, 7 with aortic regurgitation, 6 with mitral stenosis, and 5 with
      mitral regurgitation. All underwent transesophageal echocardiography (before
      aortic cross-clamping: T-pre and 60 minutes after aortic declamping: T-60). The
      short-axis view at the papillary muscle level of the left ventricle was recorded
      and anterior areas were assessed. RESULTS: The magnitude of cyclic variation at T
      pre and T-60 was 9.4 +/- 2.5 dB and 8.8 +/- 3.0 dB, and the ratio was 97 +/- 32%.
      Fractional shortening at T-pre and at T-60 was 27 +/- 7% and 20 +/- 9%, and the
      ratio was 79 +/- 44%. Recovery of magnitude was ahead of recovery of fractional
      shortening. The percent recovery of magnitude at T-60 did not correlate with
      aortic cross-clamping time (p = 0.91), postoperative peak creatine kinase-MB (p =
      0.4), or catecholamine dosage (p = 0.13), but correlated with preoperative left
      ventricular mass index (p < 0.01). In patients with aortic stenosis, the percent
      recovery of magnitude at T-60 (66 +/- 4%) was significantly lower than in those
      with other types of valvular disease. CONCLUSIONS: The recovery of magnitude of
      cyclic variation of ultrasonic integrated backscatter provides early assessment
      of myocardial injury, particularly in severely hypertrophied hearts, during
      reperfusion after aortic declamping in open heart surgery.

PMID- 11517579
TI  - Predicting blood transfusion factors in coronary artery bypass surgery.
AB  - OBJECTIVE: Blood conservation has become one of the most important issues in
      cardiac surgery. We clarified preoperative predictors of the need for blood
      transfusions during coronary artery bypass graft surgery. METHODS: Subjects were
      89 patients--66 men (74%) and 23 women (26%) 40 to 84 years old (mean: 66.2 +/-
      8.3 years)--undergoing isolated coronary artery bypass surgery from September
      1997 to December 1999. Of these, 66 patients (74%) received transfusion during
      hospitalization and 23 (26%) did not. Nine risk factors detected by univariate
      study were entered in a multivariate logistic regression model of the
      relationship between preoperative variables and blood transfusion. RESULTS:
      Independent predictors were emergency surgery (P = .0023), lower hematocrit (P =
      .0027), older age (P = .0043), and the presence of peripheral vascular disease (P
      = .0070). Optimal cutoff of hematocrit for blood transfusion was 39% and age 64
      years via receiver-operating characteristics curves based on the relation between
      sensitivity and specificity. CONCLUSION: Patients older than 64 years with
      hematocrit less than 39% and/or peripheral vascular disease should be treated
      routinely using preoperative storage of autologous blood whenever the patient's
      condition permits. For patients undergoing emergency surgery, further studies are
      required, including lowering transfusion threshold and using determinants other
      than hematocrit.

PMID- 11517580
TI  - Toxicity and pharmacokinetics of isolated lung perfusion with cisplatin in rat.
AB  - OBJECTIVE: This study was designed to evaluate the toxicity and the
      pharmacokinetics of cisplatin administered via isolated lung perfusion in Fischer
      344 rat. METHODS: Toxicity study; Cisplatin dosages of 3.3, 5.0, 6.7, and 10.0
      mg/kg were injected intravenously in four groups, respectively. Cisplatin dosages
      of 3.3, 5.0, and 6.7 mg/kg were perfused via isolated lung perfusion in a further
      three groups, respectively. The maximum tolerated dosage of cisplatin was
      determined by assessing the survival rate on day 21. Pharmacokinetics study;
      Animals received 6.7 mg/kg of cisplatin intravenously or 3.3 mg/kg of cisplatin
      via isolated lung perfusion. The cisplatin levels of the lung were measured by
      flameless atomic spectrometry. RESULTS: Toxicity study; The maximum tolerated
      dosage of cisplatin via intravenous injection was 6.7 mg/kg, and via isolated
      lung perfusion was 3.3 mg/kg. Pharmacokinetics study; The cisplatin level in the
      perfused lung was significantly higher than that in the lung of the animal
      treated intravenously (16.6 +/- 6.2 micrograms/g of tissue and 7.5 +/- 3.2
      micrograms/g of tissue, respectively) (p = 0.0096). CONCLUSION: Isolated lung
      perfusion with 3.3 mg/kg of cisplatin was pharmacokinetically superior to the
      maximum tolerated intravenous injection of cisplatin.

PMID- 11517581
TI  - Right atrial myxoma complicated with pulmonary embolism.
AB  - A 25-year-old woman was admitted to our hospital with chest pain and dyspnea, and
      was diagnosed as having a right atrial myxoma complicated with pulmonary
      embolism. An emergency operation was performed with cardiopulmonary bypass. A
      papillary pedunculated tumor was found having a narrow-based attachment to the
      free atrial wall. After the tumor was carefully removed together with the atrial
      wall around the attachment, pulmonary embolectomy was performed. Several
      fragments of the tumor were removed, and sufficient back-flow from the pulmonary
      artery was established. The postoperative course was uneventful. However, a non
      perfused area was observed in the left lower lung on pulmonary hemodynamic
      scintigraphy at 3 months after the operation. Long-term observation is required
      due to the high risk for metastasis and recurrence, and further surgical
      treatment remains the most appropriate treatment option. A second operation may
      be needed to prevent progression in complications.

PMID- 11517582
TI  - Aortic valve replacement in a heavily calcified "porcelain" aorta.
AB  - Although a heavily-calcified so-called "porcelain" aorta is encountered
      infrequently, its association presents a formidable problem in cardiac surgery.
      Here we describe a case of severe aortic stenosis and coronary artery disease
      combined with the circumferentially calcified aorta. The patient was a 63-year
      old man who successfully underwent double coronary artery bypass grafting and
      aortic valve replacement during hypothermic perfusion through the right axillary
      artery with endoaortic balloon occlusion, followed by minimal endarterectomy of
      the calcified plate along the aortotomy, and closure of the aorta buttressed with
      bovine pericardium under circulatory arrest.

PMID- 11517583
TI  - Multiple thymoma with myotonic dystrophy.
AB  - A case of multiple thymoma associated with myotonic dystrophy is reported. The
      patient was a 42-year-old man who had two separate encapsulated thymoma in the
      anterior mediastinum, at 3 cm in diameter on the right side, and at 4 cm in
      diameter on the left. Extended thymo-thymomectomy was performed. Microscopically,
      the tumor in the right thymic lobe was predominantly mixed type, and that in the
      left predominantly epithelial type. Neuromuscular disease appeared to develop,
      with severe sputum retention in the larynx and he was referred to neurology at 6
      months after surgery. On examination, he presented a characteristic hatchet face,
      muscle atrophy, muscle weakness, percussion myotonia and grip myotonia, and
      diagnosis was revised to be multiple thymoma associated with myotonic dystrophy.
      This association is extremely rare. It is difficult to clarify whether this
      association was a syndrome or coincidence.

PMID- 11517584
TI  - Left ventricular free wall rupture possibly induced by coronary spasm. Surgical
      repair in the emergency room.
AB  - A 68-year-old woman complained of chest discomfort after a traffic accident in
      which she driving hit a child. At about twenty-five minutes later, she went into
      sudden cardiogenic shock due to acute myocardial infarction caused by non
      occlusive intracoronary thrombosis without significant organic coronary stenosis
      and without any sign of extraluminal contrast pooling on coronary angiography.
      She was transported to our emergency room by ambulance because of cardiac
      tamponade caused by a left ventricular free wall rupture following the acute
      myocardial infarction. On arrival, she was near cardio-pulmonary arrest on
      intraaortic balloon pumping. We performed emergency open cardiac massage and
      pericardiotomy. The hairline perforation responsible for the blowout-type left
      ventricular free wall rupture was successfully closed with Teflon-reinforced
      sutures. In conclusion, it was strongly suspected that the present case of left
      ventricular free wall rupture was caused by acute myocardial infarction due to
      intracoronary thrombosis following coronary spasm without significant organic
      coronary stenosis or rupture of atheromatous plaque.

PMID- 11517585
TI  - Cancer of the gastric tube reconstructed through the posterior mediastinal route
      after radical surgery for esophageal cancer.
AB  - Among 750 patients diagnosed with esophageal carcinoma in our department between
      1972 and 1997, we reviewed our 10 cases in which cancer occurred within gastric
      tubes reconstructed through the posterior mediastinal route after radical surgery
      for esophageal cancer. The interval between esophagectomy and cancer onset in the
      reconstructed gastric tube was relatively long (mean interval: 72 months). Five
      of our 10 subjects had gastric tube cancer detected at follow-up endoscopy. Four
      underwent total or partial gastric tube resection with open thoracotomy using
      colonic or jejunal reconstruction; 3 underwent endoscopic resection. To the best
      of our knowledge, this is the first report on patients undergoing total resection
      of gastric tubes reconstructed through the posterior mediastinal route after
      esophagectomy and rereconstruction using the pedicled colon for the gastric tube
      cancer.

PMID- 11517586
TI  - Metastatic thyroid cancer manifesting as a mediastinal mass in a man with an
      aberrant right subclavian artery.
AB  - We treated a case of thyroid cancer manifesting as a mediastinal mass, completely
      resecting it without difficulty despite a vascular anomaly. An asymptomatic 42
      year-old woman was admitted with a mediastinal mass. Ten years earlier, she had
      undergone surgery for a thyroid tumor diagnosed as follicular adenoma. She also
      had an aberrent subclavian artery anomaly with a non-recurrent laryngeal nerve,
      radiographically recognized preoperatively. The mediastinal mass was completely
      resected through median sternotomy. Pathological examination showed the previous
      thyroid tumor had been follicular carcinoma, and that the mass was a mediastinal
      node metastasis from the thyroid cancer. Preoperative recognition of the vascular
      anomaly was helpful in completing resection, in addition to safe, quick surgical
      procedures.

PMID- 11517587
TI  - Simultaneous total arch replacement and abdominal aortic surgery.
AB  - It is common to encounter patients with coexisting aortic arch aneurysm and
      abdominal aortic lesions. We conducted simultaneous total arch replacement and
      abdominal aortic surgery in 3 patients having such lesions. Mean operative time
      was 511 minutes and no in-hospital mortality occurred. Postoperative respiratory
      failure was observed in an 80-year-old patient who recovered and all three
      patients were discharged in good condition. No other postoperative complication
      was seen. Simultaneous total arch replacement and abdominal aortic surgery may
      thus offer advantages to patients with such double aortic lesions if it can be
      conducted safely.

PMID- 11517588
TI  - Right atrial rupture in blunt chest trauma.
AB  - The mortality rate from cardiac rupture by blunt chest injury is high. Here, we
      report a case of 27-year-old male who suffered a right atrial rupture by blunt
      chest injury and was successfully treated. The hemodynamics were stabilized by
      pericardiocentesis with a 5F Pigtail catheter for cardiac tamponade and rapid
      fluid transfusion. Then the right atrial rupture was repaired without a
      cardiopulmonary bypass. The postoperative course was uneventful, and the patient
      was discharged on the 14th postoperative day.

PMID- 11517589
TI  - "Are there so many adult ductal aneurysms?" This term may be misleading for
      pathogenesis and choice of surgical procedure.

PMID- 11517590
TI  - [Post-transcriptional gene silencing and virus resistance].
AB  - Post-transcriptional gene silencing(PTGS) is a defense mechanism of plants
      against foreign nucleic acids, such as virus infection. The mechanism results in
      sequence-specific degradation of nucleic acids, including endogenous mRNA,
      transgene mRNA and virus RNA. PTGS was first discovered in transgenic plants, and
      since then, similar mechanism has been found in fungi and animals. It appears
      that PTGS is initiated by aberrant RNA and double-stranded RNA in the cell. An
      enzyme similar to RNA-dependent RNA polymerase has been identified in various
      plants, which plays a key role in the PTGS process. It is hypothesized that PTGS
      might be the natural mechanism of plants against virus infection. To support this
      hypothesis, scientists from several laboratories have discovered PTGS suppressors
      encoded by virus genomes, and the suppressors identified so far are all viral
      pathogenicity determinants, such as viral movement protein.

PMID- 11517591
TI  - [Estimate the safety of baculovirus insecticides: the history and the status
      Quo].
AB  - This article reviews the evaluation of security of baculovirus used as a
      pesticide. Since 1970s, the scholars have done a lot of experiments with kinds of
      baculovirus to test the security of a large number kinds of living things even
      our human beings. Almost all experiments proved that baculovirus is secure, but
      some experiments came to different conclusions. These gave rise to great debate
      twice when they were published, but these conclusions have been proved to be
      wrong with later test by other scientists or the author himself. Since 90s
      baculovirus have been used a great deal as the vector to express the foreign
      gene. Some of them reported the expression in mammalian cells, which brought the
      suspicious of the baculovirus safety. This article made an analysis and a
      conclusion about them. Also, this article laid emphasis on the security of
      recombination baculovirus with the results of the security experiment of self
      made recombination baculovirus pesticide. In the last analysis, this article
      draws a conclusion that the baculovirus and recombinant baculovirus insecticides
      are secure.

PMID- 11517592
TI  - [The new antiendotoxin strategies].
AB  - Lipopolysaccharide(LPS) is important in the pathogenesis of sepsis infected by
      gram-negative bacteria in humans, and part or all of this pathophysiology is
      mediated by a complex secondary inflammatory response. Administration of purified
      LPS or a variety of LPS-free recombinant mediators can reproduce much of the
      pathophysiology of gram-negative sepsis. There has been an explosion of new
      information over the last several years regarding the interactions of LPS with
      proteins and cells. Blocking sepsis at the bacterial toxin level is appealing
      because it is upstream, so that the secondary pathologic inflammatory cascade may
      be limited or prevented. A variety of antiendotoxin strategies have been
      proposed. Therapies under investigation include agents that bind and neutralize
      LPS, agents or systems that enhance LPS clearance, and agents that inhibit LPS
      interaction with serum elements or cellular receptors.

PMID- 11517593
TI  - [Advances in the expression of foreign genes in Hansenula polymorpha].
AB  - Hansenula polymorpha is a potential host for foreign gene expression, which has
      been applied widely in academic studying and industry application. It has a
      number of advantages of expressing genes derived from eukaryotic organisms, such
      as mitotically stable recombinant strains, faithful processing of the produced
      polypeptides, and high productivity et al. Numerous foreign proteins with high
      commercial value have been expressed successfully in H. polymorpha, among which
      some have been launched on the market. In this review, the favorable
      characteristics of this system for foreign gene production and new advances are
      described.

PMID- 11517594
TI  - [Purification and characterization of recombinant human interleukin 11 which
      expressed by Pichia pastoris].
AB  - This study first time report a method to purify the rhIL-11 which expressed by
      Pichia pastoris. rhIL-11 was secreted into the supernatant and collected by
      centrifugation. The purity of rhIL-11 reached 97% through the steps of
      ultrafiltration, SP Sepharose FF, Phenyl Sepharose HP and Sephadex G25. Analysis
      of SDS-PAGE, Western-blotting, IEF, RP-HPLC, Mass spectrometer, N and C terminus
      amino acid sequence and bioactivity was conducted. All the analysis results
      proved that the rhIL-11 expressed by Pichia pastoris was the same as Neumeg which
      was expressed in E. coli with fusion expression system. So it is possibly a
      cheaper and easier method to produce rhIL-11 for clinical use.

PMID- 11517595
TI  - [Overexpression of artificial synthetic gene of Aspergillus niger NRRL3135
      phytase in Pichia pastoris].
AB  - The phytase gene of Aspergillus niger NRRL3135 was modified with a deletion of
      intron and signal coding sequence. Then, according to the codon preference of
      Pichia pastoris, modified phyA gene was artificially synthesized and cloned into
      expression vector of pPICZ alpha A. The recombinant plasmid was transformed into
      chromosome of Pichia pastoris X-33 strain by electroporation. The results of SDS
      PAGE and enzymatic kinetic analysis proved that the recombinant phytase was
      secreted into culture medium with nearly same character of natural phytase. After
      screening for high level productive yeast strains, a strain named SPAN-III
      produced recombinant phytase with 165,000 u/mL under the condition of shake
      cultivation. It will satisfy the demand for industrialized production in some
      degree.

PMID- 11517596
TI  - [Function of the leaky UGA codon in ssRNA plant virus genomes].
AB  - The opal mutation (UGA) at nucleotide 2670-2672 in the replicase gene of the
      attenuated tomato mosaic virus K (ToMV-K) mainly contributes to the virus
      attenuation based on a series of studies on the viral attenuation mechanism. From
      analysis and comparison between the replicase gene mutation point of ToMV-K and
      the related regions of all plant viruses containing the leaky UGA, we have found
      that some characters, including the CGG motif, alpha-helix structure and some
      specific amino acids, are, presumably, able to helpfully confer the readthrough
      mechanism. Finally, some other ssRNA plant viruses like PVX, PVY, CMV have been
      analyzed. We found that their genomic modifications and viral attenuations could
      be explored according to the mutation mode of the ToMV-K replicase.

PMID- 11517597
TI  - [The primary role of central region of HC-pro of potato Y potyvirus in synergism
      of plant viruses].
AB  - Five deleted mutants of HC-Pro gene of Chinese isolate of potato Y potyvirus (PVY
      C) were obtained by PCR mutation, and their plant expression vectors were
      constructed. They were transformed into tobacco K326 (Nicotina tabacum cv. K326)
      mediated by Agrobacterium. PCR and Southern blot analysis revealed that PVY-C HC
      Pro gene and its deleted mutants were integrated into tobacco genome, and Western
      blot analysis showed that they were all expressed in transgenic tobacco plants.
      Furthermore, infection test demonstrated that the central region of PVY-C HC-Pro
      can mediate synergism of PVY-C/cucumber mosaic cucumovirus (CMV) and PVY-C/potato
      X potexvirus (PVX), identifying that it is functional domain in synergism.

PMID- 11517598
TI  - [Clone and expression of human soluble CD14 and study of its function].
AB  - Human soluble CD14(sCD14) cDNA fragment was amplified using total RNA extracted
      from U937 cells by RT-PCR of sCD14 gene, and the recombinant expression plasmid
      pEF1/HisC/sCD14 348aa was constructed. Then the expression in eukaryotic cell was
      carry out by liposome transfection method. It demonstrated that the expression
      level was relatively high by scanning map identification. The expressed product
      was purified by immunoaffinity chromatography and the purity was above 90%. The
      changes of CD14 brought by LPS stimulating U937 cell proved the product had the
      function of combine with LPS.

PMID- 11517599
TI  - [Studies on transgenic tobacco plants expressing two kinds of insect resistant
      genes].
AB  - A synthetic Bt cry1Ac gene fussed with a secretary signal coding sequences at 5'
      end and a modified gna gene were used to construct a plant expression vector
      pBSGS1M+ and this vector was transferred into tobacco (Nicotiana tabacum L.) by
      Agrobacterium-mediated transformation method. Results of PCR, Southern blot and
      Slot blot analysis indicated that both the chimeric Bt cry1Ac and gna genes were
      integrated into the genomes of transformed plants. Western blot analysis
      indicated that at least the cry1Ac protein was produced in transgenic plants.
      Upon insect bioassay using cotton bollworm (Heliothis armigera Hubner), the
      mortality of insect larvae on 60% regenerated plants reached 100% in 5 days post
      infestation and the growth of the survived larvae was seriously inhibited; The
      results from insect bioassay with peach aphid (Myzus persicae) showed that the
      transgenic plants were aphid-resistant, evidenced by a 50%-60% reduction in aphid
      population density, even over 80% for some individual transgenic plants. These
      results reflect that the modification of the two insect resistant genes and
      construction of the expression vector are correct and could be valuable for later
      application in crop breeding for insect resistance.

PMID- 11517600
TI  - [Inhibition effect in vitro of purified endostatin expressed in Pichia pastoris].
AB  - Endostatin is a newly found inhibitor of angiogenesis, which is identified as c
      terminal 184 amino acid fragment of collagen XVIII NC1-domain. A 570 bp cDNA
      fragment of endostatin has been amplified by PCR from a commercial human fetal
      liver cDNA library. After subcloned into the yeast vector pPIC9 and subsequence
      to prove its correctness, Pichia pastoris was transformed with the recombinant
      pPIC9-endostatin. The expressed endostatin in P. pastoris was purified by heparin
      sapherose affinity chromatography. It's purity identified by SDS-PAGE thin layer
      scanning analysis was up to 98.7% and its Mol. Weight measured by MS was 20.34
      kD. The expression level was up to 40 mg/L. The first fifteen amino acid sequence
      of the N-terminal was completely identical with the inner sequence C-terminal
      fragment of collagen XVIII NC1 domain as has been designed. Bioassay indicated
      that the recombinant endostatin can inhibit angiogenesis stimulated by bFGF in
      CAM test and also the proliferation of both HUVEC and ECV304 in an in vitro test.

PMID- 11517601
TI  - [Simultaneous expression of chicken anaemia virus proteins VP1 and VP2 in
      silkworms].
AB  - By cloning vp1 and vp2 genes of chicken anaemia virus into transfer vector
      pBacPAK8, recombinant transfer plasmids pBac-vp1 and pBac-vp2 were obtained. Then
      BmN cells were co-transfected with linearized baculovirus Bm-BacPAK6 DNA and
      above two recombinant plasmids respectively, recombinant viruses Bm-vp1 and Bm
      vp2 were constructed and used to co-infect silkworms to express recombinant
      proteins. The results indicated that recombinant VP1 and VP2 could induce the
      corresponding antibody in chickens using immunofluorescence assay and the
      expression products could protect filial generation from the attack of CAV.
      Recombinant BmNPV expressing VP1 and VP2 is, therefore, a great hopeful
      production system for a subunit vaccine against CAV infection.

PMID- 11517602
TI  - [Construction of transgenic rice populations by inserting the maize transponson
      Ac/Ds and genetic analysis for several mutants].
AB  - An efficient and rapid gene transformation system of rice mediated by
      Agrobacterium tumefaciens was used. Calli induced from immature and mature
      embryos of Zhonghua No. 11, a japonic rice variety, were cultured with the A.
      tumefaciens strain EHA105 harboring the superbinary plasmid pDsBar1300 or pUBITs
      separately, and more than 400 independent transgenic lines inserted Ds element or
      Ac fragment were obtained. Some visible mutants in T0 or T1 generation were
      found, consisting of disease resistance, albino, dwarf, male sterile, chlorosis,
      early heading, late heading, stripe, etc. From the phenotype analysis, a few
      mutants such as dwarf and male sterile seemed to be linked to the Basta
      resistance and the transposon.

PMID- 11517603
TI  - [Cloning of promoter of banana fruit-specific ACC synthase gene and primary study
      on its function].
AB  - Based on our cDNA sequence of ACC synthase gene expressed specifically in banana
      fruit, we cloned the 5'-flanking proximal region of 1197 bp and distal region of
      1556 bp via walking on unknown region of genomic DNA by an improved adaptor
      ligation PCR, and created a 2591 bp fragment containing a promoter region of 2505
      bp and a transcriptional region of 86 bp. The entire 2.5 kb promoter and 5
      different 5' deletion variants were fused to the GUS (beta-glucuronidase) cDNA
      sequence and introduced into leaf, root and fruit cells of banana plant via
      particle bombardment separately. The results of transient gene expression assay
      indicated that the obtained promoter region could direct fruit-specific gene
      expression. The regulatory region for fruit-specificity was possibly located in
      the region from -1111 to +1 and a positive regulatory region may locate between
      nucleotide -1111 to -608.

PMID- 11517605
TI  - [Application of a gel chromatography renaturing way on low molecular single-chain
      urokinase mutant(DscuPA-32K)].
AB  - A recombinant mutant gene with thrombolytic and antithrombolytic bifunction was
      expressed in E. coli. Owing to two reasons of high molecular weight and over
      expression, dscuPA existed in inclusion body form. The protein of inclusion body
      was inactive protein. In order to obtain active protein, inclusion bodies should
      be denatured and then renatured. We performed a novel way named gel
      chromatography column renaturation way. Compare with traditional renaturation
      way, this refolding approach had some obvious advantages, such as low cost and
      high recovery, and accomplished the preliminary purification step of desired
      protein(DscuPA-32K). Especially to proteins that easily became inactive and
      degradation, this approach might have good prospect.

PMID- 11517604
TI  - [Cloning, sequence analysis of deacetoxycephalosporin C synthetase/hydroxylase
      gene cefEF].
AB  - Chromosomal DNA preparations were made form the fungi C. acremonium and A.
      chrysogenum respectively by a method using 1-Chloro methyl benzene solution. Then
      the cefEF gene of deacetoxycephalosporin C synthetase/hydroxylase was amplified
      by polymerase chain reaction. The cefEF gene could only be amplified from the
      chromosomal DNA of A. chrysogenum. This fragment about 1.0 kb was cloned into
      pGME-T vector and then sequenced. The sequence indicates that the cloned cefEF
      gene contains 999 nucleotides encoding for 333 amino acids and there are three
      bases and two amino acids different from those that have been reported. Both of
      the two amino acids are not in active site. The result also indicates that the
      reported C. acremonium or A. chrysogenum generating deacetoxycephalosporin C
      synthetase/hydroxylase corresponds with A. chrysogenum but not C. acremonium in
      China.

PMID- 11517606
TI  - [Effects of ammonia on cell metabolism in the culture of recombinant CHO cells].
AB  - The effects of ammonia on metabolism of glucose, glutamine and other amino acids
      in the batch culture of recombinant CHO cells were investigated. It was showed
      that the yields of cells to glucose, glutamine and other consumed amino acids
      decreased with the increase of initial ammonia concentrations. In the batch
      culture with initial ammonia concentration 5.66 mmol/L, the yields of cell to
      glucose and glutamine reduced 78% and 74%, respectively, compared to that with
      ammonia initial concentration 0.21 mmol/L, and the yields of cells to other
      consumed amino acids also reduced 50%-70%. The metabolic pathways were altered in
      the cultures with the higher ammonia concentrations. The glucose consumption was
      more prone to form lactate by anaerobic metabolism. In the glutamine metabolic
      process, the reaction of glutamate to alpha-ketoglutarate by the glutamate
      dehydrogenase was inhibited by ammonia, and that by the glutamate amino
      transferase was facilitated. However, the yields of glutamate to glutamine
      decreased with the increase of ammonia concentrations, showing that the reaction
      of glutamate to alpha-ketoglutarate was inhibited by ammonia as a whole.

PMID- 11517607
TI  - [Effects of nutrition condition on pcDNA3-HBS plasmid DNA production].
AB  - To investigate the effects of nutrition condition on plasmid DNA production,
      Escherichia coli JM109 containing plasmid pcDNA3S-HBA was grown in different
      culture media. Results show that carbon source, nitrogen source affected plasmid
      DNA yield significantly. Glucose and peptone was selected, since they were
      preferable to other investigated carbon source and nitrogen source. In M9P
      medium, the appropriate concentration of(NH4)2SO4 was important for plasmid DNA
      production, Gly, Asp, Gln were formulated into the M9G medium because they served
      as the nitrogen donors for nucleotides synthesis. With addition of 1.2 g/L Asp,
      1.0 g/L Gln and 0.4 g/L Gly into M9G medium, plasmid DNA yield was 25 mg/L after
      20 h culture. Foreign nucleotides distinctively affected plasmid DNA production.
      With addition of 0.4 g/L nucleosides mixture of thymidine and cytidine(moles
      fraction of thymidine:cytidine = 1:1) into M9P medium, plasmid DNA yield was 35
      mg/L.

PMID- 11517608
TI  - [High expression of rabbit sperm membrane protein rSP10 in Escherichia coli and
      preparation of its specific antisera].
AB  - To study the position and immunogenicity of rSP10, the rabbit rsp10 gene which
      did not include sequences coding for signal peptides was inserted into expression
      vector pET30a. An in-frame fusion protein was made such that a His6 stretch was
      produced at the N terminus of re-rSP10. High expression was obtained, the amount
      of re-rSP10 up to 67% in the total bacterial protein. The re-rSP10 was purified
      by DEAE chromatography and the yield of purified re-rSP10 was approximately 50
      micrograms/mL of culture. Western blotting analysis of re-rSP10 with rabbit
      polyclonal sera raised against rabbit sperm membrane protein showed that the
      synthesized antigen possessed immunogenicity of rSP10. Specific antisera against
      re-rSP10 was induced using purified re-rSP10 as an antigen. The motility of
      capacitated sperms were affected but no aggregation was observed.

PMID- 11517609
TI  - [Exogenous pGH gene localization on chromosomes of the transgenic pigs].
AB  - The pUC19-OMT plasmids were cut by Ssp 1 and the products in 900 bp were
      recovered from low-melting agarose gel and used as probes which were labeled by
      Digoxigenin. After being denatured, the probes were dropped on the chromosome
      samples which were also denatured to anneal with them. The anti-digoxigenin
      antibodies labeled with colloidal gold were used to act with the chromosome
      samples. In order to localize the exogenous pGH genes(porcine growth hormone
      gene) on chromosomes detected with optical microscope and improve the
      sensitivity, digoxigen gold signals are amplified by silver precipitation. After
      calculating the number of silver grains on every chromosome under the optical
      microscope, we analyzed the data with statistical methods. The results show that
      the integrating sites of exogenous pGH genes are very different among the
      positives. However, it is clear that the exogenous genes in one are always of the
      tendency to integrate in one specific site on a certain chromosome. These data
      are of great significance for studying the site-specific integration and the
      expression efficiency of exogenous genes in the future research.

PMID- 11517610
TI  - [Study on the DNA vaccine against foot-and-mouth disease virus using the heavy
      chain constant region of swine IgG as the carrier for peptide epitopes].
AB  - The peptide of amino acids 141-160 of VP1 protein of foot-and-mouth disease virus
      (FMDV) is a major B cell epitope and the peptide of amino acids 21-40 is an
      important T cell epitope. In this study, the DNA fragments of 141-160 and 21-40
      peptide epitopes of a strain of type O FMDV was chemically synthesized and
      arranged into a tandem repeat 141-160 (20AA)-21-40 (20AA)-141-160 (20AA). This
      tandem sequence was fused to the 3' end of the heavy chain constant region gene
      of swine immunoglobulin G and was then cloned into mammalian expression vector
      pCDM8 to form a recombinant plasmid pCDM8FZ3. After pCDM8FZ3 was inoculated
      intramuscularly into guinea pigs, it elicited a neutralizing antibody response
      and a specific spleen T cell proliferative response, and 66% of the vaccinated
      animals were protected from viral challenge. Our study indicated that the heavy
      chain constant region of swine IgG can act as the carrier protein for FMDV
      peptide epitopes, and pC-DM8FZ3 is a potential DNA vaccine candidate to prevent
      FMDV infection.

PMID- 11517611
TI  - [Structural and functional study of prokaryotic enhancer-like element VV1 from
      vaccinia virus].
AB  - Enhancer VV1 (about 283 bp) is selected as the target to analyze its structure
      and function systemically. Stepwise deletion experiment is used to identify the
      functional domain of VV1 element. The results suggest that the 20 bp at 5'
      terminal and 20 bp at 3' terminal are important to the activity of VV1, for
      without either of them its activity decreased greatly. Furthermore, the 30-50 bp
      at 5' terminal is essential to its activity, without which will lead to complete
      loss of its activity. By random mutagenesis assay it is found that base mutation
      can regulate the activity of enhancer VV1 positively or negatively. The more the
      activities of mutants descend, the more mutations take place. For singlebase
      mutation, the activities change relatively little, and most of the mutations
      always occur in the 50 bp at the 5' terminal.

PMID- 11517612
TI  - [Cloning of the sugar related biosynthesis gene cluster from Streptomyces
      tenebrarius H6].
AB  - Streptomyces tenebrarius H6 produces a complex of aminoglycoside antibiotics,
      such as apramycin, tobramycin and kanamycin B etc. To study the apramycin
      biosynthetic genes the genomic library from the Streptomyces tenebrarius H6 was
      established using E. coli/Streptomyces shuttle vector pKC505 by in vitro packing.
      The probability of finding a specific gene from the library composed of 3,000
      colonies was over 99.9%. According to the highly conserved sequence of the genes
      involved in 6-deoxyhexose biosynthesis, primers were designed and 0.6 kb fragment
      homologous to strE gene was obtained by PCR. 30 positive clones were found from
      the genomic library of S. tenebrarius H6 with the 0.6 kb fragment as a probe.
      Overlapped regions were localized by Southern hybridization and putative sugar
      related biosynthetic gene cluster was mapped by restriction enzyme digestions. An
      ORF of dTDP-glucose-4,6-dehydratase gene consisted of 1,132 bp, designated as
      aprE, was obtained and submitted to GenBank under the accession number of
      AF306787. A DNA sequence highly homologous to strL coding dTDP-4-dehydrorhamnose
      reductase was found linked with aprE gene.

PMID- 11517613
TI  - [The metabolism of trehalose and intracellular glycerol in Candida krusei
      responding to high osmosis].
AB  - The trehalose and intracellular glycerol contents of osmotolerant yeast Candida
      krusei cells rapidly increased in response to the medium containing NaCl.
      Addition of NaCl at early exponential phase or steady phase increased trehalose
      content only, but the content of extracellular glycerol increased gradually.
      Development of resistance was accompanied by accumulation of trehalose and was
      apparently unrelated to intracellular glycerol content which was always low under
      these conditions. There seems to be an overlap function between trehalose and
      glycerol in Candida krusei cells in response to the osmotic conditions.

PMID- 11517614
TI  - [Growth and metabolism of human skin fibroblasts cultured on microcarriers].
AB  - Human foreskin fibroblasts were cultured in vitro on microcarriers in spinners
      and traditional static flasks. The cultured cells obtained with these approaches
      were compared in cell shape, cell growth, cell production, and the metabolisms of
      glucose, lactate, and ammonium. The cells from microcarrier cultures through
      medium exchange were 8 times more than those from traditional static flasks. It
      was found that the specific growth rate and specific glucose consumption rate in
      microcarrier spinner cultures were 0.64/d-1 and 5.56 mmol/10(9) cell/d,
      respectively, higher than those in static flask cultures. However, the average
      lactate yield on glucose consumption in spinner cultures was only 0.955
      mmol/mmol, lower than that in static flask cultures, 1. 125 mmol/mmol. This
      indicated that the energy metabolism in spinner cultures was significantly more
      efficient than that in static flasks. The experimental results from this work
      suggest that the microcarrier culture system is a suitable way to expand the
      seeding cells for tissue engineering, due to its ideal cultivation environment
      provided.

PMID- 11517615
TI  - [Cloning and expression of maltooligosyltrehalose synthase from Sulfolobus
      acidocaldarius in Escherichia coli].
AB  - The gene of MTSase (maltooligosyltrehalose synthase) from Sulfolobus
      acidocaldarius ATCC49426 was amplified by PCR. The primers were designed
      according to the published sequence of homologous gene from Sulfolobus
      acidocaldarius ATCC33909. This gene was inserted into the plasmid pBV220 and the
      resultant recombinant plasmid pBV220-GT was transformed to E. coli DH5 alpha. The
      activity of recombinant enzyme was about 10 u/g(wet cell). In order to improve
      the expression level of target protein, some nucleotides in the 3' and 5' of the
      gene were modified to optimize the second structure of mRNA by PCR amplification
      using the new primers devised according to the biosoftware GOLDKEY2.0. As a
      result, the activity of recombinant enzyme increase to 19.8 u/g(wet cell). Then,
      the helping plasmid pUBS520 which carried the gene encoding the tRNA of rare
      codons AGG and AGA was transformed to the recombinant strain. But it took little
      effect.

PMID- 11517616
TI  - [The cloning of apple ferritin gene (Apfl) from Malus xiaojinensis Cheng et Jiang
      and its structure analysis].
AB  - The special primers were designed based on the sequence information of plant
      ferritin genes reported in the literature and used for polymerase chain reaction
      (PCR) with the genomic DNA of Malus xiaojinensis Cheng et Jiang in an attempt to
      clone apple ferritin gene. A single fragment of 771 bp was successfully obtained
      from the PCRs and cloned in this study. The sequence and homology analysis
      results of the fragment showed that the deduced amino acids of the fragment had a
      ninety-nine percent homology to that of the soybean ferritin gene reported by
      Lescure et al. (1991). A comparison in details of the nucleotide sequence of the
      clone and that of the soybean ferritin gene showed that they consisted of the
      same open reading frame (ORF, 753 bp) and that the cloned fragment had complete
      initial and stop codes. Within the ORF no introns were found and there were no
      nucleotide difference in the transit peptide region (TP) of the gene, but five
      nucleotide mutations were found in the mature peptide region (MP), among which
      four were synonymous mutations.

PMID- 11517617
TI  - [Study on the improvement of process technology of L(+)-tartaric acid
      fermentation].
AB  - This work proposes an improved process technology of L(+)-tartaric acid produced
      by using cis-epoxysuccinates as the substrate for fermentation. The key to the
      question is to apply dipotassium cis-epoxysuccinate as the substrate instead of
      disodium cis-epoxysuccinate. As compared with the original process technology,
      the improved one has prominent advantages: 1. High yield of acid, increased by
      20%-30% over the old one; 2. High rate of recovery, from about 60% to 80%; 3. One
      of the raw materials is cheaper, the KOH is expensive than NaOH, but half of the
      K kions could be used cyclically, and the varied products could be obtained
      easily; 4. The tough working procedure of filtration of fermented liquor could be
      evaded, the total working procedures might increase to some extent, but the cost
      of production will be reduced obviously, it is advantageous to industrial
      production.

PMID- 11517618
TI  - [Cloning, sequencing and in vitro expression of human RANTES gene].
AB  - An expected 276 bp fragment of the gene precursor encoding the signal peptide and
      mature protein of human beta-chemokine RANTES was amplified by reverse
      transcription-polymerase chain reaction (RT-PCR) from RNA of PHA-activated human
      peripheral blood lymphocytes. This putative interested gene was inserted directly
      into a T-vector and the ligation was confirmed by restriction enzyme digestion.
      The sequence data of the cloned fragment showed that it was almost identical with
      published sequences of RANTES gene, except for only one nucleotide substitution
      within the signal peptide region. The in vitro expressed recombinant RANTES
      protein was detected by the chemiluminescence enzyme-linked immune Dot blotting
      assay after combining the recombinant plasmid with the in vitro SP6/T7
      transcription and translation system. The successful cloning and expression of
      RANTES gene should shed light on future's gene therapy of AIDS.

PMID- 11517619
TI  - Perspectives. Work environment a top issue in nurse retention.

PMID- 11517620
TI  - Metaphors of learning and professionalism.
AB  - The overall health of the community is based, in part, on the degree or level to
      which individual members choose to participate as a professional. Do they remain
      on the periphery or progress to full participation in the professional
      association? CLS education has been highly successful in preparing practitioners,
      yet the educational process as a whole has failed to reach the more challenging
      goal of preparing practitioners as professionals. When designing curricula for
      educating professionals, educators need to teach the importance of a professional
      association as a critical and necessary component of the whole. Our goal should
      be to prepare "practitioners who are constantly seeking to increase their
      professional competence". To achieve this goal, practitioners must transfer
      knowledge and skills as they, with guided participation from other professionals,
      move into professional activities.

PMID- 11517621
TI  - Iron deficiency anemia due to a defect in iron metabolism: a case report.

PMID- 11517622
TI  - Using the overlapping parts of laboratory test panels to evaluate abnormal
      results.

PMID- 11517623
TI  - Carcinomatous meningitis in a patient with metastatic breast cancer.
AB  - Metastases are defined as the appearance of neoplasms in parts of the body remote
      from the site of the primary tumor. Metastasis can occur through one of three
      processes: direct seeding of body cavities or surfaces, lymphatic spread, and
      hematogenous spread. The importance of laboratory utilization in the diagnosis of
      metastasis is explored using a case study of a 39-year-old female with metastatic
      breast carcinoma to the brain. This case study was carried out using clinical
      records, laboratory results, pathology reports, and physician interviews.
      Cerebrospinal fluid was obtained and examined in hematology, chemistry, and
      microbiology. Tissue from the breast was examined both before and after
      chemotherapy. Morphologic comparisons of both primary and metastatic tumor cells
      were carried out. The breast tissue showed infiltrating mammary carcinoma, ductal
      type, with 8/11 auxiliary lymph nodes showing metastasis. Evaluations of
      cerebrospinal fluid cell count results revealed the presence of malignant cells
      in remarkable numbers. Based on cytological and hematological results, a
      diagnosis of meningeal carcinomatosis was determined and treatment was started.
      Following the intrathecal chemotherapy, serial cerebrospinal fluid examinations
      showed the percentage of malignant cells decreased and no cells were detected 11
      days after treatment. Metastasis, including meningeal carcinomatosis is a common
      occurrence with breast carcinoma. An effective chemotherapeutic treatment is
      evaluated for this disease when an accurate diagnosis is made. As demonstrated by
      this case study, proper use of the laboratory can help establish the diagnosis of
      metastasis.

PMID- 11517624
TI  - A comparison study of different methods used in the detection of Giardia lamblia.
AB  - OBJECTIVE: The purpose of this study was to compare results obtained using a
      single fecal specimen for O&P examination, direct immunofluorescent assay (DFA),
      and three immunodiagnostic techniques. DESIGN: Sixty-eight human fecal specimens
      were collected and examined by each method. The O&P and the DFA were used as the
      reference method. SETTING: The study was performed at the research laboratory in
      the Medical Technology Department at The University of Southern Mississippi.
      PATIENTS OR OTHER PARTICIPANTS: The fecal specimens were collected from
      individuals with a suspected Giardia lamblia infection. INTERVENTIONS: None. MAIN
      OUTCOME MEASURES: The amount of agreement and disagreement between methods. 1.
      The sensitivity and specificity of each method. 2. The working time and cost per
      specimen for each method. RESULTS: There was complete agreement among methods on
      52 specimens (21 positive, 31 negative). Eight specimens were positive by all
      immunologic methods, but negative by O&P. The remaining eight specimens (12%)
      demonstrated discrepancies among methods. Sensitivity and specificity of each
      assay ranged from 91% to 100% and 89% to 100%, respectively. The cost per
      specimen ranged from $11.62 for the DFA method to $32.54 for the O&P method. The
      average cost per specimen for ELISA and EIA averaged $26.86. CONCLUSION: The
      study supported findings of other investigators who concluded that immunologic
      methods have the greater sensitivity. The immunologic methods were more
      efficient, quicker, and economical than the conventional O&P method.

PMID- 11517625
TI  - Sweat chloride: quantitative patch for collection and measurement.
AB  - OBJECTIVE: To compare two quantitative pilocarpine iontophoresis tests for sweat
      chloride. DESIGN: Simultaneous right and left arm sweat tests were done with the
      Gibson/Cooke and the CF quantum technologies. SETTING: Sweat tests were performed
      in a quality controlled cystic fibrosis (CF) sweat test laboratory by an
      experienced technologist at the University of Minnesota CF Center. PATIENTS:
      Patients referred for sweat tests as well as volunteer CF and control subjects
      (50 CF and 114 'normals') were tested. INTERVENTIONS: Standard procedures were
      used for the Gibson/Cooke test (GCST). The manufacturer of the CF quantum test
      (CFQT) provided factory standardized materials. MAIN OUTCOME MEASURES: Sweat
      chloride concentration, test time, failed tests, sensitivity, specificity, and
      cost. RESULTS: Duplicate test comparing the CFQT and the GCST revealed good
      comparability (R2 = 0.9434). Sensitivity and specificity of the two methods are
      comparable at about 94% and 99% respectively. Rate of failed tests was 1% for the
      CFQT and 15% for the GCST. The CFQT and the GCST are comparable (R2 = 0.9434).
      Sensitivity (94%) and specificity (99%) are the same for both tests. CONCLUSIONS:
      The CFQT method is equal in accuracy and reliability to the more labor-intensive
      and costly GCST. Advantages of the CFQT are: the small sample size required
      (three to ten mg), decreased operator dependence, simpler to perform, and
      requires less equipment. It could be used in a clinic setting to diagnose CF in
      patients with suggestive symptoms.

PMID- 11517626
TI  - The influence of perceived professional status on the career progression of CLS
      graduates.
AB  - OBJECTIVE: To determine if the perception of clinical laboratory science (CLS),
      as a profession, influences career progression. DESIGN: A questionnaire was
      designed to collect information on job history including salary and positions
      held, reasons for leaving the field, satisfaction with the field and the
      perception of the field as a profession or a technical occupation. SETTING:
      Research facilities at the Graduate School of Public Health, San Diego State
      University, San Diego, CA. PARTICIPANTS: Graduates from the CLS program of the
      University of Minnesota Division of Medical Technology, 1923-1996, were sent
      questionnaires; 1338 (70.2%) responded. MAIN OUTCOME MEASURES: The comparison of
      career progression for those who perceive CLS to be a profession to those who
      perceive it to be a technical field. RESULTS: Seventy-seven percent of the
      respondents perceived the field to be a profession. They were 1.7 times more
      likely to have progressed in their careers than those who perceived CLS to be a
      technical field. This was reflected in the percentage achieving higher positions
      both currently and over the respondents' entire job history. CONCLUSIONS: Those
      who perceive CLS to be a profession are more likely to progress in their career
      and remain in the field of CLS.

PMID- 11517627
TI  - Changes in economically disadvantaged adolescents' knowledge and beliefs about
      HIV/AIDS.
AB  - PURPOSE: The purpose of this study was to compare HIV/AIDS related knowledge and
      beliefs in two cohorts of economically disadvantaged adolescents (n = 132).
      Participants were between 15 and 21 years old, predominately African-American and
      Hispanic, and participants in a Job Training Partnership Act (JTPA) summer
      program. The hypothesis was that adolescent HIV/AIDS-related knowledge would be
      higher in 1999 than in 1994. METHODS: A cohort of sixty-six (66) adolescents were
      surveyed in 1994 and another cohort of 66 adolescents was surveyed again in 1999,
      all participating in the JTPA program. Participants' knowledge and beliefs were
      assessed using the National Adolescent Student Health Survey. RESULTS: A
      statistically significant increase in overall HIV/AIDS knowledge occurred between
      the two measurements. Fifty-five percent (55.6%) of the 1999 cohort believed that
      HIV could be contracted by donating blood, compared to 47.5% of the 1994 cohort.
      Belief that it is more likely to become infected with the AIDS virus through male
      to male sex was higher in 1999 by 2% and was 10% higher for female to female sex.
      CONCLUSIONS: Adolescent misconceptions/misinformation, gender-based lack of
      knowledge, increased perception of immunity from HIV infection, and a reported
      reduction in health education courses were all factors in the adolescents'
      continued engagement in risky sexual activities. Given these findings, and that
      AIDS is predicted to be one of the top five causes of death among young people,
      increased gender- and ethnic-specific HIV intervention programs are recommended.

PMID- 11517628
TI  - CLT and CLS job responsibilities: current distinctions and updates.
AB  - OBJECTIVE: This study was undertaken to address the following questions: 1. What
      tasks distinguish the job of a clinical laboratory scientist (CLS) from that of a
      clinical laboratory technician (CLT)? 2. What changes in role distinctions, have
      occurred for entry-level CLS and CLT practitioners over the five-year period 1993
      98? 3. What tasks have been deleted from the CLT and CLS content outlines because
      they were not frequently performed or not considered entry-level? 4. What changes
      in practice are reflected in the current job analyses? DESIGN: A national job
      analysis of tasks constituting the job of clinical laboratory scientists (CLSs)
      and clinical laboratory technicians (CLTs) was conducted in 1998-99 as part of a
      standard setting process for the certifying examinations of the National
      Credentialing Agency for Laboratory Personnel (NCA). The job analyses relied upon
      mail surveys to 1200 individuals for each job level asking respondents to
      identify tasks significant to effective practice at job entry. The task lists
      resulting from statistical analysis of those surveys were examined to answer the
      study questions. PARTICIPANTS: The sample for each survey included 1200
      practitioners, educators and laboratory managers selected at random from
      membership in professional organizations or from NCA certificant lists. Sampling
      was stratified to insure adequate practitioner representation. MAIN OUTCOME
      MEASURES: The mean rating on a four point scale for each item on the surveys was
      evaluated for overall significance as well as significance across geographic
      regions. The tasks meeting specified criteria were retained in the final task
      lists. Tasks were counted and their content evaluated to compare CLS and CLT job
      tasks. RESULTS: The response rates to the surveys were 33% for CLT and 21% for
      CLS. Reliability was judged based on average intraclass correlation coefficients
      of .86 and .82 for the CLT and CLS surveys, respectively. There were 952 tasks
      retained on the CLS content outline and 725 retained on the CLT content outline
      of the 1151 tasks on the original survey. Seven hundred and twenty two tasks were
      found on content outlines of both job levels, representing a 76% overlap. Tasks
      found only on the CLS outline included advanced technical tasks, a few management
      tasks, and more communication tasks. CONCLUSIONS: The jobs of CLS and CLT
      practitioners are distinct at job entry level with CLSs performing a broader
      array of technical and communication tasks as well as some management tasks.
      Though CLS staff uses few management skills at job entry, those tasks are
      performed by CLS staff in the laboratory and curricula must help prepare
      graduates for these tasks expected of experienced staff. CLTs perform tasks
      requiring problem solving and high level reasoning. CLT curricula must address
      the need for CLTs to perform these tasks.

PMID- 11517629
TI  - Genital HPV: links to cervical cancer, treatment, and prevention.
AB  - Human papillomavirus is one of the most prevalent sexually transmitted viruses.
      It consists of over 230 different subtypes and infects the squamous epithelial
      cells in humans producing cutaneous, mucosal, and epidermodysplasia verruciformis
      type infections. There are several risk factors for human papillomavirus
      infections. These include a sexually active life-style beginning at a young age,
      having multiple lifetime sex partners, having sex with a partner with genital
      warts, and long term oral contraceptive use. Approximately 80% of sexually active
      individuals acquire the virus in their lifetime. Clinical and laboratory
      detection of the virus consists of macroscopic, serologic, and molecular
      techniques. Although removal of the lesions is preferable, treatment of human
      papillomavirus infections may include cryotherapy, loop electrosurgical excision
      procedure, laser surgery, and drug therapy. Certain human papillomavirus
      subtypes, particularly human papillomavirus 16, have been linked to cervical
      cancer, therefore, prophylactic and therapeutic vaccines are currently being
      developed to prevent or fight the virus.

PMID- 11517630
TI  - Listeriosis: an emerging food-borne disease.
AB  - Listeriosis is a serious disease acquired by ingestion of foods contaminated with
      Listeria monocytogenes. Special populations at risk are individuals who are
      immunocompromised to some extent. The most common clinical findings include
      meningitis, septicemia, encephalitis, and intrauterine/cervical infections. Food
      related listeriosis is an unusual occurrence but it is now being thought of as a
      new, and emergent illness. Numerous types of food products have been implicated
      in listeriosis infections, but of particular concern are ready to eat products
      such as lunchmeats, hotdogs, ham/chicken salad, sausages, and roast beef.
      However, to ensure food safety, there are several methods employed to detect L.
      monocytogenes in food products and the severity of listeriosis warrants stringent
      guidelines in food processing facilities. Nevertheless, proper food preparation
      and handling must be emphasized and individuals who are at an increased risk for
      the disease must be apprised on how to prevent the occurrence of infection.

PMID- 11517631
TI  - Hereditary hemochromatosis: a case study and review.
AB  - Hereditary hemochromatosis (HH) is a disorder of iron regulation that leads to
      excessive iron absorption. Over time, the resultant iron overload and deposition
      in tissue leads to various chronic diseases and premature death. Even though it
      is the most common genetic disorder among Caucasians in the U.S., hereditary
      hemochromatosis often goes undetected or unrecognized by healthcare providers.
      Laboratory tests provide effective, inexpensive means of screening for and
      confirming hereditary hemochromatosis. The clinical laboratory also plays a key
      role in hereditary hemochromatosis treatment, reduction of iron stores through
      therapeutic phlebotomy.

PMID- 11517632
TI  - Chronic iron overload and toxicity: clinical chemistry perspective.
AB  - The content of body iron is regulated primarily by absorption since humans have
      no physiological mechanism by which excess iron is excreted. This regulation,
      however, is not absolute. Many factors such as the content of diets, iron doses,
      life styles, etc. influence iron absorption. In the past, nutrition programs for
      iron fortification and the ingestion of iron preparations have been widely
      practiced because of the seriousness of worldwide iron deficiency. Also, we now
      know that a significant number of asymptomatic people carry the hemochromatosis
      gene, HFE, indicating that these people have the potential to accumulate excess
      body iron in their lifetime. Excess body iron can be highly toxic. This toxicity
      involves many organs leading to a variety of serious diseases such as liver
      disease, heart disease, diabetes mellitus, hormonal abnormalities, dysfunctional
      immune system, etc. The tissue damage associated with iron overload is believed
      to result primarily from free radical reactions mediated by iron. Iron is an
      effective catalyst in free radical reactions. The diseases associated with iron
      overload can be managed effectively or prevented. Therefore, early diagnosis of
      iron overload and appropriate therapy are critical. By providing the necessary
      laboratory data, clinical chemistry laboratories can play the pivotal role in the
      management of these health problems.

PMID- 11517633
TI  - Breast cross-examination.

PMID- 11517634
TI  - Debating the criteria for brain death.

PMID- 11517635
TI  - Debating the criteria for brain death.

PMID- 11517636
TI  - Debating the criteria for brain death.

PMID- 11517637
TI  - Be careful with the term "bone loss".

PMID- 11517638
TI  - The error of our ways.

PMID- 11517639
TI  - Take a lesson from the drug companies.

PMID- 11517640
TI  - Choosing family medicine.

PMID- 11517641
TI  - Hand-held brain extenders.

PMID- 11517643
TI  - Quality of congestive heart failure treatment at a Canadian teaching hospital.
AB  - BACKGROUND: Practice guidelines for the management of congestive heart failure
      (CHF) emphasize the need for assessment of left ventricular function and
      treatment with angiotensin-converting enzyme (ACE) inhibitors. However, previous
      studies have shown that many patients do not receive these tests or medications.
      The objective of this study was to evaluate the compliance of physicians at a
      large Canadian teaching hospital with published CHF management guidelines.
      METHODS: We conducted a retrospective review of the charts of 200 patients
      admitted to Sunnybrook & Women's College Health Sciences Centre, Toronto, in 1997
      for whom CHF was the diagnosis most responsible for the hospital admission.
      Quality of care was measured with 3 indicators: the use of left ventricular
      function testing to determine systolic versus diastolic dysfunction; the
      prescription of ACE inhibitors to appropriate patients (those with systolic
      dysfunction, no contraindications to ACE inhibitor therapy and no angiotensin II
      receptor blocker use); and the prescription of target doses of ACE inhibitors.
      RESULTS: Of the 200 patients 177 (88.5%) received left ventricular function
      testing before or during their hospital stay; of the 177, 117 (66.1%) had
      systolic dysfunction. A total of 100 patients were considered to be ideal
      candidates for ACE inhibitor treatment. Of the 100, 89 (89.0%) received ACE
      inhibitors; however, only 23 (23.0%) were prescribed target doses.
      INTERPRETATION: Most patients who had CHF at this Canadian hospital received left
      ventricular function testing and ACE inhibitor therapy. Future educational
      efforts should focus on the importance of adequate dosing of ACE inhibitors.

PMID- 11517642
TI  - Waiting times from abnormal breast screen to diagnosis in 7 Canadian provinces.
AB  - BACKGROUND: Delay to breast cancer diagnosis following an abnormal screening
      result is associated with anxiety and personal disruption. We assessed the
      patterns and timeliness of diagnostic follow-up after breast cancer screening for
      women with abnormal results who attended organized screening programs in 7
      provinces. METHODS: Using data from the Canadian Breast Cancer Screening
      Database, we identified 203,141 women aged 50-69 years who underwent screening in
      1996 through provincially organized breast cancer screening programs in British
      Columbia, Alberta, Saskatchewan, Manitoba, Ontario, Nova Scotia and Newfoundland.
      We prospectively followed women with an abnormal screening result through to the
      completion of the assessment process. We evaluated the waiting times from
      screening examination to first assessment, from screening examination to first
      imaging, from screening examination to diagnosis and from first assessment to
      diagnosis for 13,958 women, stratified according to screening program, mode of
      detection, whether a biopsy was performed and whether cancer was diagnosed.
      RESULTS: We observed considerable variations between and within programs in the
      time to diagnosis. The median time from screening examination to first assessment
      was 2.6 weeks. The median time from screening examination to diagnosis was 3.7
      weeks; this time increased to 6.9 weeks for women undergoing biopsy. Even when no
      biopsy was performed, 10% of the women waited 9.6 weeks or longer for a
      diagnosis, as compared with 15.0 weeks or longer for 10% of the women undergoing
      biopsy. Among the women who had a biopsy, the use of core biopsy was associated
      with a shorter median time to diagnosis than was open biopsy, and those found to
      have cancer had shorter waiting times than women with benign biopsy findings.
      INTERPRETATION: Women undergoing assessment of an abnormal breast cancer
      screening result waited many weeks for a diagnosis, especially when a biopsy was
      performed. To ensure that targets for timeliness, adopted nationally in 1999, are
      realized, improved models of care or dissemination of existing efficient
      techniques to reach a diagnosis will be needed.

PMID- 11517644
TI  - A population-based study of potential brain injuries requiring emergency care.
AB  - BACKGROUND: Brain injury is an important health concern, yet there are few
      population-based analyses on which to base prevention initiatives. This study
      aimed, first, to calculate rates of potential brain injury within a defined
      Canadian population and, second, to describe the external causes, natures and
      disposition from the emergency department of these injuries. METHODS: We studied
      all cases of blunt head injury that resulted in a visit to an emergency
      department for all residents of Greater Kingston during 1998. We used data from
      the Canadian Hospitals Injury Reporting and Prevention Program (CHIRPP) and
      augmented this by examining all records of emergency or inpatient care received
      at all hospitals in the area. RESULTS: In 202 (27%) of 760 cases of head injury,
      there was potential for brain injury. Annual rates of potential brain injury were
      16 and 7 per 10,000 population for males and females respectively. CT was
      performed on 114 (56%) of 202 cases, of which 60 (53%) demonstrated an
      intracranial pathology, with 11 (10%) showing a diffuse axonal injury pattern on
      the initial scan. Falls from heights accounted for 14 (47%) of 30 injuries
      observed in children aged 0-9 years. Individuals aged 10-44 years sustained 32
      (63%) of 51 motor vehicle injuries, 15 (88%) of 17 bicycle injuries, 22 (100%) of
      22 sports injuries and 8 (89%) of 9 fight-related injuries. Falls accounted for
      15 (71%) of 21 injuries among adults aged 65 years or more. INTERPRETATION: The
      results indicate the relative importance of several external causes of injury.
      The findings from our geographically distinct population are useful in
      establishing rational priorities for the prevention of brain injury.

PMID- 11517645
TI  - Past infection with hepatitis A virus among Vancouver street youth, injection
      drug users and men who have sex with men: implications for vaccination programs.
AB  - BACKGROUND: In Canada, inactivated hepatitis A vaccines are targeted selectively
      at those at increased risk for infection or its complications. In order to
      evaluate the need for routine hepatitis A vaccination programs in Vancouver for
      street youth, injection drug users (IDUs) and men who have sex with men (MSM), we
      determined the prevalence of antibodies against hepatitis A virus (HAV) and risk
      factors for HAV in these groups. METHODS: The frequency of past HAV infection was
      measured in a sample of Vancouver street youth, IDUs and MSM attending outreach
      and STD clinics and needle exchange facilities by testing their saliva for anti
      HAV immunoglobulin G. A self-administered, structured questionnaire was used to
      gather sociodemographic data. Stepwise logistic regression was used to evaluate
      the association between presumed risk factors and groups and past HAV infection.
      RESULTS: Of 494 study participants, 235 self-reported injection drug use, 51 were
      self-identified as MSM and 111 met street youth criteria. Positive test results
      for anti-HAV were found in 6.3% of street youth (95% confidence interval [CI]
      2.6%-12.6%), 42.6% (95% CI 36.2%-48.9%) of IDUs and 14.7% (95% CI 10.4%-19.1%) of
      individuals who denied injection drug use. Among men who denied injection drug
      use, the prevalence was 26.3% (10/38) for MSM and 12% (21/175) for heterosexuals.
      Logistic regression showed that past HAV infection was associated with increased
      age and birth in a country with high rates of hepatitis infection. Injection drug
      use among young adults (25-34 years old) was a significant risk factor for a
      positive anti-HAV test (p = 0.009). MSM were also at higher risk for past HAV
      infection, although this association was nominally significant (p = 0.07).
      INTERPRETATION: Low rates of past HAV infection among Vancouver street youth
      indicate a low rate of virus circulation in this population, which is vulnerable
      to hepatitis A outbreaks. An increased risk for HAV infection in IDUs and MSM
      supports the need to develop routine vaccination programs for these groups also.

PMID- 11517646
TI  - Physicians' perceptions of the benefits and risks of warfarin for patients with
      nonvalvular atrial fibrillation.

PMID- 11517647
TI  - Breast cancer diagnosis: what are we waiting for?

PMID- 11517648
TI  - Management of congestive heart failure: how well are we doing?

PMID- 11517649
TI  - The privacy paradox: laying Orwell's ghost to rest.

PMID- 11517651
TI  - Not even the Canada Health Act is sacred, vows Romanow.

PMID- 11517650
TI  - Update on intravenous tissue plasminogen activator for acute stroke: from
      clinical trials to clinical practice.
AB  - Tissue plasminogen activator (tPA) injected intravenously within 3 hours of
      symptom onset has emerged as a treatment option for acute ischemic stroke.
      Although controversial and not universally accepted, its use in carefully
      selected patients is supported by evidence from randomized controlled trials and
      by mounting community experience. In this paper we review the literature
      published in the past 5 years regarding the safety, clinical trial efficacy and
      real-world effectiveness of intravenous tPA for stroke. First we review data from
      the phase III clinical trials on which approval for tPA is based. Then we
      summarize a growing literature of postmarketing phase IV studies and discuss the
      limitations and challenges that lie ahead. Our aim is to provide clinicians with
      an overview of this evolving therapy.

PMID- 11517652
TI  - Raccoon rabies secures 2 bridgeheads in Canada.

PMID- 11517653
TI  - Drugs taking bigger bite of health care pie.

PMID- 11517654
TI  - Emergency contraceptive pill hits Ontario market.

PMID- 11517655
TI  - A primer for patients' use of medicinal marijuana.

PMID- 11517656
TI  - Sunlight exposure and non-Hodgkin's lymphoma.

PMID- 11517657
TI  - [The fine structure of the midgut of mite Myobia murismusculi].
AB  - The pattern of digestion in females of Myobia murismusculi was studied with light
      and electron microscopy. The midgut consists of a stomach and two pairs of blind
      caeca. The stomach is connected dorsoposteriorly with the excretory organ, that
      leads externally to an anal opening via the cuticle-lined rectum. No differences
      were found between the stomach and its caeca. The midgut epithelial cells are of
      a single type. Their fine structure and gut contents greatly vary depending on
      different physiological conditions of the mite. Four stages of digestion can be
      shown with electron microscope. Pino- and phagocytose takes place in the same
      cells. At an active stage of digestion numerous pinocytic canals were observed in
      the midgut cells. At each stage of the digestive cycle groups of flat cells are
      present in the midgut epithelium. They do not take part in the intracellular
      digestion of food material. Cytoplasmic processes from the underlying cells of
      coxal glands project into the midgut cells through the orifices in the gut basal
      lamina.

PMID- 11517658
TI  - [Functional heterogenicity of human blood neutrophils: generation of oxygen
      active species].
AB  - Kinetics of neutrophil inactivation was investigated in vitro by Nitroblue
      tetrazolium (NBT) test in the process of their contact with the substrate. It has
      been shown that the previous thermostatation results in an exclusive inactivation
      of neutrophils with high reaction ability leading to their complete inactivation.
      Such an inactivation is a consequence of cell contacts with the substrate, whose
      chemical structure and physicochemical properties define the process
      regularities. The neutrophil inactivation is probably not a consequence of the
      contact itself but may follow the next scheme: stimulus (contact with substrate)-
      generation of reactive oxygen metabolites--inactivation. Two functional unequal
      classes of neutrophils were differentiated on the basis of different levels of
      their reactive oxygen metabolite generation, and on their ability to
      inactivation. In vitro cells of one of these classes actively generate reactive
      oxygen metabolites to be inactivated in consequence of interaction with the
      substrate, whereas cells of the other class produce reactive oxygen metabolites
      less actively and are nor inactivated. Evidently, in vivo cells of the are
      phagocytes and those of the latter fulfill other functions.

PMID- 11517659
TI  - [Somatic polyploidy in neurons of the gastropod molluscs. II. Dynamics of DNA
      synthesis in the process of postnatal growth of CNS neurons in Succineid snail].
AB  - A study was made of the age dynamics of polyploidization and dynamics of DNA
      synthesis in neuron cell nuclei during the postnatal growth of the gastropod
      pulmonate snail Succinea lauta. According to cytophotometrical results, the
      degree of polyploidization in neuron nuclei increases from young to adult
      individuals, varying from 2c to 16,384c. In the visceral complex, the maximum and
      medium ploidy values of the neuron nuclei are higher by almost 4-8 times than
      those in cerebral and pedal ganglia. The medium level of ploidy in adult snails
      increases by 5.7 times in the visceral complex of ganglia and by 4.1-4.2 times in
      the pedal and cerebral ganglia. According to 3H-thymidine autoradiography, DNA
      synthesis in neuron nuclei occurs during the whole life of the snail. In young
      individuals the neurons have the highest activity of DNA synthesis--the index of
      labeled nuclei of neurons making in total 50.2%. In older age, a steady decrease
      in the index of labeled nuclei is observed--in total to 35.8% and 7.0% in small
      and large adult snails, respectively. The state of summer hibernation completely
      stops DNA syntheses in neurons, but emergency from hibernation is accompanied by
      restoration of DNA syntheses.

PMID- 11517660
TI  - [Evolutionary regularities of somatic polyploidy in salivary glands of the
      Gastropod molluscs. II. Subclass Pectinibranchia: order Anisorbranchia].
AB  - Salivary glands of 5 species of gastropod molluscs of the order Anisobranchia,
      the most ancient order within the subclass Pectinibranchia, have been
      investigated by histological and cytochemical methods, including DNA
      cytophotometry. Glandular cells of the following types were recognized: granular
      cells (with glycoproteid granular inclusions), mucocytes-I (including sulfatic
      acid mucopolysaccharides), mucocytes-II (including neutral and acid
      polysaccharides and proteins), and epithelial ciliated cells. All the described
      cell types are considered to be independent and their morphofunctional
      characteristics coincide with those of salivary gland cells of the gastropod
      molluscs of subclasses Cyclobranchia and Scutibranchia. It has been shown that
      somatic polyploidy in salivary glands in the Anisobranchia molluscs, likely as in
      those of other Archaeogastropoda (Cyclobranchia and Scutibranchia), is actually
      absent.

PMID- 11517661
TI  - [Primary culture of epithelial secretory cells from venom gland of the common
      adder Vipera berus].
AB  - A primary culture of epithelial secretory cells from the venom gland of Vipera
      berus was obtained. The cells adhered to collagen 1 and to a mixture of adhesion
      proteins (Matrigel), proliferated and retained the features of differentiation.
      Electron microscopy demonstrated the presence of all ultrastructures typical of
      these cells in vivo, a full complex of intercellular junctions, and cellular
      membrane polarity. The immunohistochemistry confirmed the capacity of secretory
      cells to synthesize venom in culture. We have studied the role of carbochole, an
      agonist of M-cholinoreceptor, in the initiation of the secretory cycle in cells
      in vitro. We propose that M-cholinoreceptors may play an important role in the
      initiation of the secretory cycle in vivo.

PMID- 11517663
TI  - [Extreme cytokinesis phenomenon in the phenotype of meiotic mutation pam of Zea
      mays].
AB  - Our study of cytological phenotype of meiotic mutation pam resulted in detecting
      a failure of cytokinesis in mutant pollen mother cells in the form of a block of
      fusion of membrane vesicles of the cell plate, and an impossibility of formation
      of daughter cell membranes. The mutation does not disturb the division spindle
      structure and function. Asynchrony of meiosis in pam is the result of arrest of
      pollen mother cells at metaphase 1 and metaphase 2.

PMID- 11517662
TI  - [Differential decondensation of mitotic chromosomes in SPEV tissue cultured cells
      induced by repeated hypotonic shock ].
AB  - A new method of differential decondensation of mitotic chromosomes has been
      proposed by means of repeated treatment of live cells with 15% Hanks' balanced
      salt solution. The procedure of cell treatment includes three stages: the first
      hypotonic shock, cultivation in isotonic medium, and the second hypotonic shock.
      As a result, after a standard methanol-acetic acid fixation and Giemsa staining
      some discrete Giemsa-positive globules are revealed in mitotic chromosomes. Such
      globules are symmetrically arranged in axial regions of sister chromatids. The
      comparative analysis of marker chromosomes has revealed a topological conformity
      of these globules to G-bands of chromosomes. It has been shown that it is the
      first hypotonic shock that triggers induction of structural modification of
      chromatin in interphase nuclei and in mitotic chromosomes. Of interest is the
      fact that the effect of the first shock is prolonged in time and is realized
      during at least one cell cycle, with the normal structure of mitotic chromosomes
      being restored after S-phase of the successive cell cycle.

PMID- 11517664
TI  - [Actin-regulated water permeability of two transport channels of plasmodesmata in
      roots of winter wheat cultivars varying in drought resistance].
AB  - In roots of 5-6-day old seedlings of three cultivars of the winter wheat, varying
      in drought-resistance: Bezostaya 1 (low resistant), Mironovskaya 808 (resistant),
      and Albidum 114 (highly resistant) water permeability of two transport channels
      of plasmodesmata was studied at the action of cytochalasin B, which is known to
      inhibit polymerization of cytoskeleton actin filaments, by a pulse method of NMR,
      on the background of increasing water loss in the seedlings. It has been found
      that the registered coefficients of water self diffusion, two of which (D2 and
      D3) depend on the water permeability of different transport channels of
      plasmodesmata, differ in opposite directions. This may suggest that in roots of
      drought-resistant plants, after a moderate water loss, a diffusive water flow
      through the cytoplasmic symplast increases (demonstrated by an increase of D2),
      while that through the vacuolar symplast decreases (seen by an increase of D3).
      After a high water loss in seedlings, we noticed an even greater increase in
      water permeability of the cytoplasmic symplast, and a decrease in water
      permeability of the vacuolar symplast, however, in the roots of low resistant
      cultivars these changes were poorly expressed, if at all. Under stress-less
      conditions cytochalasin B would result in an increased water transport through
      the cytoplasmic channel of plasmodesmata due apparently to a destruction of their
      actin-myosin sphincters. Both weak and average degrees of water loss would
      strengthen the cytochalasin B exerted influence on plasmodesmal water
      conductance, that may testify to a synergetic action of these two factors. After
      a significant water loss this action was kept only partially, because the
      inhibitor, on blocking the cytoplasmic channel, did increase at the same time the
      effect of water stress, limiting water flows through the vacuolar symplast and,
      simultaneously, raising the water inflow to the apoplast.

PMID- 11517665
TI  - [Effect of synthetic cationic peptides on activation of the adenylyl cyclase
      signaling system by biogenic amines in muscle tissue of molluscs and rats].
AB  - The hormone-sensitive adenylyl cyclase signaling system (ACS), made of serpentine
      receptor, heterotrimeric G-protein and enzyme adenylyl cyclase (AC), regulates a
      wide spectrum of growth and metabolic processes in the cell. Molecular mechanisms
      of functional coupling of ACS components still remain obscure. We examined the
      influence of synthetic cationic peptides Ac-Ala-His(Ala)2-His-Ala-NH2 (I), Ac-Ala
      His-(Ala)3-His-(Ala)2-His-Ala-NH2 (II), and Ac-(Pro)2-His-(Ala)2-His-(Ala)3-His
      (Ala)2-His-Ala-NH2 (III) on the basal AC activity and that stimulated by
      nonhormonal (NaF) and hormonal reagents (serotonin--molluscs, beta-isoproterenol-
      rats) in smooth muscles of the freshwater bivalve molluscs Anodonta cygnea and in
      skeletal muscles of rats. Peptides II and III (the latter more effective) were
      shown to decrease hormone-stimulated AC activity in both tissues, in a dose
      dependent manner. Peptide III strongly reduced NaF stimulating effect to AC,
      which suggests the involvement of this peptide in the functional coupling of both
      receptors with G-proteins, and of G-proteins with AC. A correlation was found
      between the efficacy of peptide action on the functional activity of ACS
      components and peptide length. As shown by IR-spectroscopy, in water all peptides
      can form helical structures. However, alpha-helicity of peptides I and II was
      higher than that of peptide III, which does not conform to a power series in
      efficacy of these peptides. Thus, it is the length of cationic peptides that
      plays a key role in hormonal regulation of the functional activity of ACS,
      especially on the step of receptor-G-protein coupling.

PMID- 11517666
TI  - [Internal symmetry in nucleotide sequences of genes encoding the dolichol cycle
      enzymes].
AB  - In genes alg5, alg8 and swp1 of Saccharomyces cerevisiae, gpt of
      Schizosaccharomyces pombe and human gene alg6, encoding the dolichol cycle
      enzymes, a mirror type internal symmetry was found. The symmetry was detected in
      both complete nucleotide sequences and sequences of the first, second and third
      nucleotide bases of codons. In the encoding gene regions the density of single-
      and double-point centres of the internal symmetry for sequences of the second
      bases was higher in comparison with the sequences of the first and third bases of
      codons, whereas in the noncoding regions degrees of symmetry of the first, second
      and third bases sequences did not differ significantly. A clear positive
      correlation was revealed in the internal symmetry distribution in the second base
      sequences of codons in genes, on the one hand, and in the gene encoded amino acid
      sequences, on the other hand. The maximum internal symmetry of gene segments
      encoding the functionally important regions of proteins was found at the level of
      the second base sequences. The obtained results corroborate a hypothesis about
      the determining role of the second bases of codons in encoding amino acid
      residues. The investigation of internal symmetry in nucleotide sequences has
      first shown the existence of internal symmetry at the level of gene primary
      structure.

PMID- 11517667
TI  - [Karyotypes and chromosome polymorphism of two phytophilous species of
      chironomids--Glyptotendipes mancunianus and G.imbecillis (Diptera, Chironomidae].
AB  - Detailed cytophotomaps of polytene chromosomes have been made for Glyptotendipes
      mancunianus (2n = 8) and G. imbecillis (2n = 8). In the karyotype of G.
      imbecillis a greater quantity of a near-centromere heterochromatin is noted. In
      the karyopool of G. mancunianus 10 sequences are revealed. Specimens with
      heterozygous inversions make 39%, the average number of heterozygous inversions
      per specimen is 0.34. In the karyopool of G. imbecillis 11 sequences have been
      met. Specimens with heterozygous inversions make 69%, the average number of
      heterozygous inversions per specimen is 1.68.

PMID- 11517668
TI  - [Karyofund of Chironomus plumosus (Diptera, Chronomidae) in the Palearctic
      region].
AB  - Quantitative and qualitative analyses of chromosomal polymorphism in 38
      Palearctic populations of Chironomus plumosus were made. It was shown that most
      of the populations studied were highly polymorphic: in average 63.2 +/- 4.0% of
      larvae were heterozygous for inversions with 0.95 + 0.08 heterozygous inversion
      per larvae. Polymorphism on the size of centromeric heterochromatin and the
      presence of B-chromosomes were observed in many populations studied. The
      karyofund of Ch. plumosus in Palearctic was estimated. In total 35 banding
      sequences were found in Palearctic Ch. plumosus. Fifteen banding seguences have
      been described for the first time. On mapping the used banding sequences, we
      employed the conventions of Keyl (Keyl, 1962; Devai et al., 1989) and Maximova
      (Maximova, 1976; Shobanov, 1994a) for arms A, C, D, E and F, and the conventions
      of Maximova for arms B and G.

PMID- 11517669
TI  - [Analysis of natural diversity of symbiotic relationships in the Paramecium
      bursaria--Holospora curviuscula system].
AB  - Bacteria of the genus Holospora belong to obligatory endonucleobionts of ciliates
      of the genus Paramecium. The bacteria show specificity towards the particular
      host species and the types of nuclei they infect: macro- or micronuclei. During a
      long-term screening of P. bursaria clones, belonging to three different syngens,
      Holospora inhibited cells of two syngens only. Using the number of host clones
      and symbiont isolates, it was shown that H. curviuscula was unable to pass
      successfully through the syngen barrier even under experimental infection.
      Considering the species level of specificity in Holospora associations of P.
      caudatum we suggest the existence of a greater evolutionary divergence in P.
      bursaria syngens than in syngens of P. caudatum. We have revealed that in
      incompatible combinations "host clone--symbionts isolate" the complicated
      bacterial life cycle may be blocked at definite stages depending on genetic
      features of both partners. Thus, the recognition of the full block spectrum could
      break the continuous infection process down to independently controlled steps.
      The block spectrum revealed in the system of P. bursaria--H. curviuscula
      demonstrates its significant similarity to block spectra of other systems within
      the Holospora--Paramecium complex. A block of transverse binding formation has
      been first revealed in Holospora dividing in the nucleus.

PMID- 11517670
TI  - The dynamics of rhythmical aiming in 2D task space: relation between geometry and
      kinematics under examination.
AB  - We explored a two-dimensional task space variant of the classical rhythmical
      Fitts' task in which participants were asked to sequentially cross four targets
      arranged around the extreme points of the major axes of an ellipse. Fitts' law
      was found to adequately describe the changes in movement time with the variations
      in task difficulty (ID), but the 1/3 power-law relating curvature and tangential
      velocity of the trajectory did not resist the increase in ID. Kinematic analyses
      showed that the behavioral adaptation to the ID resulted in an increase in the
      contribution of non-linear terms to the kinematics along the two axes of task
      space. Moreover, a limit cycle model (combining Rayleigh damping and Duffing
      stiffness, as in one-dimensional Fitts' task) captured such a behavior. In such a
      context, Fitts' law and the 1/3 power law appear as surface relations that emerge
      from parametric changes in a dynamical structure that captures the nature of
      Fitts' task.

PMID- 11517671
TI  - The effect of timing of a perturbation on the execution of a lifting movement.
AB  - Anticipation to the mass magnitude is important in lifting, but underestimation
      of a mass, in contrast to overestimation, does not cause major movement
      disturbances. This may be caused by corrections in muscle activity before the
      object is actually lifted. This study was designed to assess the importance of
      these corrections during the loading phase for the execution of a lifting
      movement when the mass is underestimated. Ten subjects lifted a box (1.6 kg), of
      which the mass was increased by 10 kg without them knowing so. The mass was added
      either before the box had been lifted from the ground (perturbation before lift
      off, PBL) or right perturbation after lift-off (PAL). In the PBL condition back
      muscle activity was increased before lift-off. Even though this early corrective
      response could obviously not occur in the PAL condition, the lifting movement was
      executed without clear problems. In sum, corrections in muscle activity before
      lift-off are not necessary for adequate correction of a perturbation induced by
      an unexpected heavier object.

PMID- 11517672
TI  - Effect of localized muscle fatigue on vertical ground reaction forces and ankle
      joint motion during running.
AB  - The purpose of this study was to examine the changes in the vertical ground
      reaction force (VGRF) and ankle joint motion during the first 50% of the stance
      phase of running following fatiguing exercise of either the dorsiflexors or the
      invertors of the foot. VGRFs, sagittal and rearfoot kinematic data were collected
      from 11 female recreational runners running at 2.9 m/second on a treadmill prior
      to and following localized muscle fatigue of either the invertors or dorsiflexors
      of the right foot. Loading rate of the impact peak force significantly increased
      following fatiguing exercise of the dorsiflexors, while the peak magnitudes of
      the impact and push-off forces remained unchanged. There were significant
      decreases in dorsiflexion at heel contact, but no significant difference in any
      rearfoot motion parameters tested following dorsiflexor fatigue. Following
      fatiguing exercise of the invertors, impact peak magnitude, push-off peak
      magnitude and the rate of decline of the impact peak force significantly
      decreased; there was no change in the loading rate of the impact peak force.
      Invertor fatigue also resulted in a less inverted foot position at heel contact,
      but there were no significant differences in any other kinematic parameters
      tested. The results demonstrate that localized muscle fatigue of either the
      invertors or dorsiflexors can have a significant effect on the loading rates,
      peak magnitudes and ankle joint motion seen during running. These changes, due to
      localized muscle fatigue, may play a role in many common lower extremity running
      injuries.

PMID- 11517674
TI  - Using skeleton-based tracking to increase the reliability of optical motion
      capture.
AB  - Optical motion capture provides an impressive ability to replicate gestures.
      However, even with a highly professional system there are many instances where
      crucial markers are occluded or when the algorithm confuses the trajectory of one
      marker with that of another. This requires much editing work on the user's part
      before the complete animation is ready for use. In this paper, we present an
      approach to increasing the robustness of a motion capture system by using an
      anatomical human model. It includes a reasonably precise description of the
      skeleton's mobility and an approximated envelope. It allows us to accurately
      predict the 3-D location and visibility of markers, thus significantly increasing
      the robustness of the marker tracking and assignment, and drastically reducing-
      or even eliminating--the need for human intervention during the 3-D
      reconstruction process.

PMID- 11517673
TI  - Processes underlying adaptation to tempo changes in sensorimotor synchronization.
AB  - In synchronizing finger taps with an auditory sequence, a small sudden tempo
      ("step") change in the sequence tends to be followed by rapid adaptation of the
      tapping period but slow adaptation of the relative phase of the taps, whereas a
      larger step change leads to initial period overshoot followed by rapid adaptation
      of both period and phase [M.H. Thaut, R.A. Miller, L.M. Schauer, Biological
      Cybernetics 79 (1998a) 241-250]. Experiment 1 replicated these findings and
      showed that the transition between the two patterns of adaptation occurs near the
      perceptual detection threshold for a tempo change. A reasonable explanation of
      these data was provided by a dual-process model of internal error correction [J.
      Mates, Biological Cybernetics 70 (1994a) 463-473, 70 (1994b) 475-484], with the
      added assumption that one process (period correction) depends on conscious
      awareness of a tempo change whereas the other (phase correction) does not. This
      assumption received support in Experiment 2, where a synchronization-continuation
      tapping task was used in combination with perceptual judgments to probe into the
      process of period correction following step changes. The results led to the
      conclusion that rapid adaptation of the tapping period to a small, undetected
      tempo change is in fact due to rapid internal phase correction, whereas slow
      adaptation of the relative phase of the taps is due to slow internal period
      correction.

PMID- 11517675
TI  - Deterministic variability and stability in detuned bimanual rhythmic
      coordination.
AB  - We examined the effects of crossing different degrees of cooperation and
      competition on inphase and antiphase 1:1 frequency locked coordination of left-
      and right-hand-oscillated pendulums. Degree of cooperation was manipulated
      through the joint frequency of oscillation specified by a metronome (the higher
      the frequency, the weaker the cooperation), and degree of competition by length
      (and, therefore, preferred frequency) differences between the two pendulums (the
      greater the difference, the stronger the competition). Increasing competition was
      accompanied by either decreasing cooperation (for six participants) or increasing
      cooperation (for six different participants). On each trial, a participant
      attempted to produce a steady-state phase relation phi for a given combination of
      competition and cooperation. Numerical simulations of the extended Haken-Kelso
      Bunz (HKB) equation were used to predict (a) the patterns of shift in phi from
      either 0 or pi radians due to the different competition-cooperation relations and
      (b) the patterns of variability in phi. It was expected that the HKB equation
      would be successful in respect to (a), which it was, but not in respect to (b).
      The observed failure to confirm (b) was expected from the variability due to the
      different nonharmonic dynamics of the component oscillators, a source of
      variability not included in the HKB equation. The experimental results together
      with simulations and analyses of the phase-plane trajectories of the component
      oscillators suggest the operation of deterministic in addition to stochastic
      variability in the phase relation of contralateral limbs.

PMID- 11517676
TI  - From one doctor to another.

PMID- 11517677
TI  - Medem's E-cure.

PMID- 11517678
TI  - The use of beta-blockers in congestive heart failure.

PMID- 11517679
TI  - Elliptic centric contrast enhanced MRA provides high resolution, noninvasive
      evaluation of the carotid/vertebral arteries.

PMID- 11517680
TI  - Reducing pressure ulcers in long-term care.

PMID- 11517681
TI  - Bone densitometry in assessment of bone mineral density.
AB  - Osteoporosis is a serious disease characterized by low bone mineral density.
      Osteoporosis affects 24 million people annually and may be responsible for
      devastating hip, wrist and spinal fractures. Bone mineral density is considered
      the best predictor for osteoporotic fracture. Progress has been made toward
      noninvasive assessment of bone mineral density to provide early diagnosis of
      osteoporosis. A variety of methods are used to assess bone mineral density. These
      methods are presented and dual energy X-ray absorptiometry is discussed in
      detail.

PMID- 11517682
TI  - [Dietary fibers of secondary vegetable raw material for correction of
      carbohydrate and lipid metabolism in laboratory animals].
AB  - Drop of consumption by the population of dietary fibers is one of the causes of
      increase of sickness rate by diabetes in particular, and violation of
      carbohydrate metabolism in general. The purpose of research is definition of a
      degree of effect of dietary fibers of by-products of grapes processing (grape
      seed-cakes and press cake of grape pyrenes in an mixture with sorbite) on a
      carbohydrate and lipide metabolism in laboratory animals. During examinations is
      detected, that the vegetable products based on dietary fibers do not have
      negative action on physical development of animals, their body weight. The
      parameters of an amount of reticulocytes, erythrocytes, lymphocytes, hematocrit
      were in normal range. In animal, receiving dietary fibers of secondary grape raw
      material in a ration, the concentration of a cholesterol in blood serum was lower
      on 2-3% (5.6-5.9 +/- 0.2 mmol/l) as against control (6.0 +/- 0.2 mmol/l). The
      basal level of a glucose has appeared equal for control: 6.1 +/- 0.5 mmol/l, and
      for others groups of rats, consuming a dietary fibers with sorbite from 5.6 +/-
      0.4 up to 6.0 +/- 0.5 mmol/l.

PMID- 11517683
TI  - [Substantiation of the need of fortification with vitamins of the diet of
      children with gastrointestinal diseases].
AB  - Surveys of 28 children have shown that 64 per cent of the children suffering from
      ulcerous disease of the stomach and the duodemun or chronic duodenitis have a
      combined deficiency of vitamin E, vitamins of the B group and beta-carotene. Diet
      No. 1 and No. 5 could not provide daily needs for vitamins. The patients were
      found to have a lower antioxidant activity of the blood serum, whereas the
      contents of hydroperoxides, double bonds and malonic dialdehydes were higher than
      in healthy children. The POL index in children with high beta-carotene deficiency
      was significantly higher than that in ailing children supplied with this
      carotenoid. Correlation analysis has revealed a reverse relationship between
      concentration of vitamin E and beta-carotene in blood serum and POL products,
      i.e. the better a child is supplied with these vitamins, the lower is the level
      of POL products. When the drink with the whole set of vitamins and an oil
      solution of beta-carotene was included in the diet of the children, it was found
      that hypovitaminosis frequency lowered with positive effects on their clinical
      condition and improved POL indexes. So there is a reason to fortify diets of
      children suffering from gastrointestinal disorders with vitamins-antioxidants.

PMID- 11517684
TI  - [Effects of anti-atherosclerotic low-sodium diet on dynamics of natural
      antibodies to angiotensin II, bradykinin and vasopressin in blood of patients
      with hypertension and obesity].
AB  - The dynamic of natural antibodies against angiotensin II, bradykinin and
      vasopressin in blood serum was studied in 75 patients with hypertension and
      obesity. Universal normalizing effect of the diet consists in decrease of levels
      of natural antibodies was found.

PMID- 11517685
TI  - [Use of organic forms of selenium in nutrition of patients with gastrointestinal
      diseases].
AB  - Selenium level was determined in sera of 27 patients including 15 patients with
      chronic gastrointestinal diseases and 12 patients with intestinal malabsorption
      after some kinds of stomach or small intestine resection. Deficiency of this
      trace element was found in 5 patients and suboptimal concentration in 4 patients
      in the first group and in 3 and 5 patients of second group respectively.
      Supplementation of patients with 45 mg of selenium organic form based on
      autolysis extract of selenious baker's yeast resulted in increase of selenium
      level in 23 (85%) patients including all of them with selenium deficiency or
      suboptimal level. It was concluded about high bioavailability of selenium in
      supplement studied. Perturbed intestinal absorption after surgical resection of
      stomach or small intestine may be considered as an indication for prophylactic
      taking of organic selenium form preparation.

PMID- 11517686
TI  - [Medical and biological assessment of genetically modified corn line MON 810
      resistant to European corn borer and line GA 21 resistant to glyphosate: a
      chemical study].
AB  - Chemical analysis of genetically modified corns MON 810 resistance to European
      corn borer and GA 21 tolerance to glyphosphate was performed. Results of these
      studies showed that there is no difference between genetically modified and
      conventional corn products.

PMID- 11517687
TI  - [Medical and biological assessment of the safety of genetically modified corn
      lines MON 810 and GA 21: a toxicological-biochemical study].
AB  - The rats were fed with the flour of corn from genetically modified corn MON 810
      and from genetically modified corn GA 21 (Monsanto Co, USA) 3 g/rat/day for 6
      months. Their blood, urea and liver were investigated to measure total protein
      and glucose levels, aminotransferase and alkaline phosphatase activities, pH,
      creatinine level as well as hepatic enzyme activity of the I and II phases of
      xenobiotic metabolism and whole and non-sedimentated lysosomal enzyme activities,
      the level of processes of lipids peroxidation and activity of antioxidant system.

PMID- 11517688
TI  - [Microecological system and its importance in evaluation of the effectiveness of
      biologically active supplements and probiotic products].
AB  - A possibility to estimate a quality of bioactive supplements and probiotical
      foods by their influence on microecological system of a gastrointestinal tract
      are exhibited as a result of multiyear research. The consist and biological
      activity of micropopulations, including the normalization of level of protective
      intestinal microflora, the increasing their antibiosis activity, the elimination
      of potentially pathogenic microorganisms, the excretion of volatile phenols and
      indican with urine, the content of volatile fatty acids, enzymes, secretory
      immunoglobulins in feces, destruction in vitro cholic acid and cholesterol etc.,
      are tested as indicators. The reasoned supposal is advanced that the wide spread
      of disbacteriosis is connected not only with changing of defence mechanisms
      (reactions) of macroorganism, but also with accumulation of pathogenic features
      in microorganisms by action of environmental factors.

PMID- 11517689
TI  - [Electrochemical methods of control of iodine contents in drinks].
AB  - The simple and express methods of determination of iodide ions (0.01-0.20
      mg/decimeter3) in iodine-enriched drinks by potentiometry and inversion
      voltamperometry were developed. The studies on influencing a storage time
      hermetically packaged carbonated beverages, a storage time of the depressurized
      drinks, stuff of ware on the contents of iodine in drinks are held.

PMID- 11517690
TI  - [5-hydroxymethylfurfural as indicator of quality of juices for child nutrition].
AB  - 132 samples of domestic and imported juices and juice concentrates for child
      nutrition were analyzed on content of 5-hydroxymethylfurfurol (5-HMF), which is
      considered as an indicator of violation of juice manufacturing technology. The
      concentrations of 5-HMF in 15.9% of domestic juice samples and 10.3% of imported
      juice and concentrate samples were found higher than 20 mg/L--maximum level
      established by AIJN for some juices and nectars. The results confirmed the
      expediency of including of HMF maximum concentration in hygienic characterization
      of fruit juices and concentrates as an indicator of violation of their
      manufacturing and storage procedures.

PMID- 11517691
TI  - [Microbiological aspect of balanced nutrition].
AB  - Analysis of modern resources of normal human microflora correction has shown an
      importance of microbiological aspect in principles of a balanced feeding for
      realization of the optimum mechanism of normal human microflora maintenance.

PMID- 11517692
TI  - [Mechanism of alcohol action on gastric secretion].
AB  - In chronic experiment on dogs (3 dogs with Pavlov's miniature stomach, 3 dogs
      with Heidenhain's miniature stomach) the mechanism of action of alcohol (8%-150
      ml) on gastric secretion was clarified. For this purpose the new inhibitor of
      gastric secretion--glycopeptide was utilized, which action was preset in
      laboratory of G.K. Shlygin. Was shown, that in effect of alcohol on gastric
      secretion take place the complicated mechanism including as a nervous regulation
      (vagus nerves), and humoral: participation of gastrin and histamine in secretory
      effect of a stomach, and also immediate effect of ethanol on acid glands.

PMID- 11517693
TI  - [Current principles of the use of laparoscopic surgery in gastroduodenal ulcer].
AB  - Comparative assessment of treatment results in 618 patients with gastroduodenal
      ulcer (GDU) was carried out. 3 groups of patients were compared. Different
      combinations of drugs were used in 384 patients, 234 patients have undergone open
      resections of the stomach or organsaving operations, 83 patients--analogous
      laparoscopic operations. Immediate and long-term results of the treatment were
      studied. After drug therapy, including antihelicobacter drugs, healing of ulcers
      was achieved in 96.9-97.9% cases. 1 year after drug therapy the recurrence of CDU
      is revealed in 16.2-20.3% patients, rate of the recurrence increases with years.
      After surgical treatment of CDU (more often in complicated course of the disease)
      rate of recurrences is 2-3 times lower (6.5-7.4% cases). Laparoscopic resections
      of the stomach and organsaving operations are atraumatic, accompanied by
      physiologic course of postoperative period and reduction of postoperative
      complication rate.

PMID- 11517694
TI  - [Hemipylorectomy with transverse pyloroplasty and vagotomy in perforating and
      bleeding ulcers of the pyloric canal].
AB  - Hemipylorectomy with transverse pyloroplasty and vagotomy was made in 922
      patients with perforating and bleeding ulcers of pyloric canal. 510 of them had
      perforation of ulcer, 412--ulcer bleeding. In all the cases ulcer was excised
      together with anterior semicircle of the pylorus, the defect was sutured
      transversely. Hemipylorectomy with transverse pyloroplasty was combined with
      (anterior selective proximal serous-muscular and posterior trunkal) vagotomy.
      Postoperative lethality in perforation of ulcer was 4.8%, in bleeding--8.2%. From
      1 year to 10 years after operation good functional results were achieved in the
      majority of the patients. This variant of organsaving operation is optimal in
      complicated ulcers of pyloric canal.

PMID- 11517695
TI  - [Transhiatal esophagectomy].
AB  - Results of 56 transhiatal esophagectomies performed for cardioesophageal cancer
      from 1985 to 1999 are evaluated. Operation was completed by one-stage plastic
      repair with gastric flap or colon. Manual transhiatal esophagectomy performed in
      35 cases led to many intraoperative complications in location of the tumor in the
      middle and top part of thoracic esophagus, including two fatal. These
      complications make manual transhiatal esophagectomy in this location of the tumor
      undesirable. Of it is indicated only in location tumor in the bottom third of the
      esophagus. In such cases instrumental transhiatal removal of the esophagus above
      the tumor is made. This method was used in 21 cases without intraoperative
      complications and lethal outcomes.

PMID- 11517696
TI  - [Diagnosis and treatment of abdominal injuries].
AB  - Results of treatment of 164 patients with combined abdominal trauma were
      analyzed. It makes sense to evaluate severity of trauma and severity of the
      patient condition by scales VPKh-MT and VPKh-SP. These scales permit to
      standardize severity of damages and choose optimum diagnostic and curative
      algorithm. The emphasis is on early ultrasonic examination of the abdomen in
      combined trauma. In obscure ultrasonic diagnosis laparoscopy is recommended, in
      severe or extremely severe condition of patients (over 31 points by scale VPKh
      SP)--laparocentesis. Choice and time of surgical interventions must be determined
      by priority of severity of damage.

PMID- 11517697
TI  - [Surgical policy in diabetic angiopathies of the lower limbs with suppurative
      necrotic lesions].
AB  - Results of treatment of 158 patients aged from 17 to 26 years with pyonecrotic
      complications of diabetic angiopathies are presented. Classification is proposed
      taking into account characteristics of purulent lesions (local, general,
      progressive), state of circulation in the damaged limb (major or collateral) and
      severity of ischemia for choice of treatment policy. Thanks to a sound policy
      based on these data recovery with limb safety was achieved in 130 (82.3%)
      patients, including 55 patients who had undergone reconstructive vascular
      operations or lumbar sympathectomy. High amputations were performed in 28 (17.6%)
      patients, in 12 of them--on the crus, and in 16--on the thigh. There were no
      lethal outcomes.

PMID- 11517698
TI  - [Surgery of bifurcation of the femoral artery in popliteal-tibial arterial
      occlusion].
AB  - In vascular surgery department of V. Vakhidov Research Center of Surgery 37
      patients with diffuse lesion of popliteal-tibial arterial segment in combination
      with stenotic lesion of profound and common femoral artery were examined and
      operated. Examination of regional circulation before operation was made with
      consideration of profundo-popliteal collateral index (PPCI) which permits to
      evaluate features and degree of lesion of deep femoral artery (DFA). Angiography
      failed to defect bifurcation of the femoral artery in 17 (48.6%) cases, in 11 of
      them stenosis of bifurcation of the femoral artery was revealed in intraoperative
      revision. In these patients PPCI was 0.34 and more, high peripheral vascular
      resistance was seen in debitometry. The authors believe that calculation of PPCI
      is one of the main methods of diagnosis of femoral artery bifurcation lesions.
      Good and satisfactory results were seen in 29 (78.3%) patients, unsatisfactory-
      in 8. Amputations were performed in 3 patients. 1 patient died. Suppuration of
      the wounds was in 6 patients, in 4 of them--in the zone of reconstructed artery
      with arrhosive bleeding. It is suggested that in diffuse lesions of arteries of
      popliteal-tibial segment examinations of regional hemodynamics and plastic repair
      of DFA are most effective.

PMID- 11517699
TI  - [Intensive preoperative hypoxic radiotherapy in combined treatment of patients
      with cancer of the colon].
AB  - Efficacy of combined treatment (203 patients) and surgical treatment (200
      patients) alone was analyzed. In combined treatment either radiation therapy (RT)
      in the dose 20 Gy over 5 days (group 1) or hypoxyradiotherapy (HRT) in the same
      doses but in combination with hypoxia (10% oxygen and 90% nitrogen--hypoxic gas
      mixture HGM-10--group 2) were used in preoperative period. In group 3 HGM-9 (9%
      oxygen and 91% nitrogen) was used as radioprotector in preoperative period but in
      increased by 25% radiation doses: total 25 Gy, 5 Gy for 5 days. In the control
      group only radical surgical treatment was performed. Preoperative irradiation
      didn't increase the rate of postoperative complications. At the same time the 5
      year survival rate was higher in all the groups of patients on combined treatment
      than in the group of patients on surgical radical treatment. In the group with
      HGM-9 and increased by 25% radiation doses postoperative complications rate was
      lower, recurrences and distant metastases occurred less frequently.

PMID- 11517700
TI  - [Surgical treatment of diffuse toxic goiter].
AB  - Surgical intervention is one of the main methods of treatment of diffuse toxic
      goiter (DTG). Comparative analysis of surgical treatment of two groups of
      patients is presented: patients of group 1 (n = 215) underwent subtotal
      subfascial resection of the thyroid gland by O.V. Nikolaev. Group 2 (n = 757)
      were operated by improved method--extirpation of larger lobe with isthmus and
      resection of the other lobe regarding the autoimmune component. Exposure of
      recurrent nerves and parathyroid glands was obligatory during operation. These
      results confirm that the improved surgical method in DTG decreases significantly
      the number of early and late postoperative complications.

PMID- 11517702
TI  - [Method of laparoscopic treatment of gastroesophageal reflux with mesh implant].
AB  - Modern potential of endoscopic surgery promoted expansion of indications for
      surgical treatment of gastroesophageal reflux disease. The majority of
      laparoscopic methods has a number of significant disadvantages. Methods of
      laparoscopic treatment of gastroesophageal reflux using the implant with partial
      anterior fundoplication or without it were developed. These methods simplify
      surgical technique, permit to save topographoanatomical relationships of organs
      and at the same time restore Hiss angle and ensure work of sphincter that satisfy
      requirements to antireflux operations.

PMID- 11517701
TI  - [Proliferative activity of the gastric epithelium: changes due to therapy in
      patients with association of gastric ulcer and diabetes mellitus].

PMID- 11517703
TI  - [Chronic appendicitis resulting in giant mucocele].

PMID- 11517704
TI  - [Genesis of solitary pulmonary cysts and their classification].

PMID- 11517705
TI  - [Pancreatoduodenal resection with stomach preservation in cancer of the
      periampullar zone and head of the pancreas].

PMID- 11517707
TI  - [Surgery in medieval Russia].

PMID- 11517706
TI  - [Current views on regeneration of the liver].

PMID- 11517709
TI  - Quackery in the incurable.

PMID- 11517708
TI  - [Clinical features, diagnosis and surgical treatment of solitary air cysts of the
      lungs].
AB  - 86 cases of solitary air cysts of the lung (6.83% of all maldevelopments) were
      analyzed. This maldevelopment of bronchial tree is found most often in men (10:7)
      and more often in the right lung than in the left (18:13). There were no clinical
      symptoms in 33 (38.37%) patients. Uncomplicated course of the disease was in 51
      (59.3%) patients, the disease was complicated by infection in 28 (32.56%)
      patients. Solitary bronchial cysts were complicated by spontaneous pneumothorax
      in 8.14% cases, by hemoptysis--in 6.98%. Roentgenography of the chest thorax on
      two projections and tomography (including CT) are enough for diagnosis of
      solitary air bronchial cysts. Bronchoscopy, bronchography and APG are not much
      informative in diagnosis of cysts and should be used on special indications.
      Cystectomy or cystectomy with partial resection of lung tissue were performed in
      67.14% patients with good results.

PMID- 11517710
TI  - Brown Medical School: class of 2001.

PMID- 11517711
TI  - Teaching professionalism.

PMID- 11517712
TI  - Why teach? A treatise in honor of Henry T. Randall, MD, the first true chairman
      of surgery, Brown Medical School.

PMID- 11517713
TI  - Precepting in a community based internal medicine teaching practice; results of a
      time-motion study.

PMID- 11517714
TI  - Physicians newly licensed in Rhode Island during 1999-2000.

PMID- 11517715
TI  - Tobacco use in households with asthmatics.

PMID- 11517716
TI  - Cancer in Rhode Island: common questions, simple answers.

PMID- 11517717
TI  - Point of view: respecting patient's wishes at the end of life: hospital and
      physician concerns.

PMID- 11517718
TI  - A running of many words.

PMID- 11517719
TI  - Windbreaks as a pesticide drift mitigation strategy: a review.
AB  - The use of natural and artificial barriers to mitigate pesticide drift from
      agricultural and forest applications is discussed. This technique has been
      considered as an alternative to current methods at a time when environmental
      concerns are under great public scrutiny. There has been a variety of research
      experiments on this subject from New Zealand to The Netherlands which have
      documented reductions in spray drift of up to 80-90%. However, there are still
      enormous data gaps to utilize this method accurately. The aerodynamic factors of
      wind barriers and shelter effects on crop growth and yield have been well
      investigated. In contrast, some of the important aspects of drift mitigation,
      e.g. porosity and turbulence, have been difficult to obtain and no standard
      methodologies are currently available to evaluate and classify windbreaks and
      shelterbelts or to determine their efficiency in reducing drift. Thus there is a
      significant opportunity to incorporate windbreaks into the tool set of drift
      mitigation tactics. Government policies, initiatives, legislation, etc, which
      currently address water quality, BMP, stewardship, buffers, etc, are issues which
      so far have not included windbreaks as a valuable drift mitigation strategy.

PMID- 11517720
TI  - Identification of a 2,6-dichloroisonicotinic-acid-sensitive protein kinase from
      tobacco by affinity chromatography on benzothiadiazole-sepharose and NIM-metal
      chelate adsorbent.
AB  - In the search for the target site of inducers of systemic acquired resistance
      (SAR), a BTH-binding protein kinase (BBPK) has been identified from tobacco by
      affinity chromatography on benzothiadiazole-sepharose (CGA 324041-sepharose) and
      NIM-metal chelate affinity resin. The substrate selectivity of the isolated
      enzyme (phosphorylation of histone type III-S, I kappa B alpha,IkB alpha
      S32A/S36A and NIM1) suggested a possible BBPK-mediated regulation of NIM1 in
      tobacco. The measurement of the effect of different SAR-inducers showed an
      inhibition of BBPK by 2,6-dichloroisonicotinic acid (INA) and, to a lower extent,
      by benzothiadiazoles and salicylic acid. Comparison between BBPK cell-free
      inhibition and in vivo PR-1 induction revealed that BBPK could be the target site
      of INA.

PMID- 11517721
TI  - Pyrethroid insecticide residues on vegetable crops.
AB  - Pyrethroid insecticides were applied on various vegetable crops as foliar
      treatments to determine dissipation rates. On Chinese broccoli (Guy Lon), Chinese
      mustard (Pak Choi) and Chinese cabbage (Kasumi, napa), fenvalerate was persistent
      with residues of 0.10, 0.14 and 0.11 mg kg-1, respectively, by day 21.
      Cypermethrin residues on head lettuce were below 0.1 mg kg-1 by day 10 but on the
      leafier romaine and endive varieties it was more persistent and required 14-19
      days to dissipate below this concentration. After three applications, residues of
      cypermethrin in harvested carrots and of permethrin in eggplant were not detected
      on the day of application. On asparagus, deltamethrin and cypermethrin residues
      declined to less than 0.1 mg kg-1 by days 1 and 2, respectively; permethrin was
      more persistent, requiring more than 2 days to decline to less than 0.1 mg kg-1.
      Deltamethrin on dry (cooking) and Spanish onions was not detected on the day of
      application. On tomatoes, the concentration of permethrin was 0.093 mg kg-1 on
      the day of application and declined to about 0.05 mg kg-1 after 2-4 days. In
      general, permethrin, cypermethrin and deltamethrin residues declined to
      acceptable concentrations within an acceptable pre-harvest interval. Fenvalerate
      may be too persistent on these speciality crops unless a maximum residue limit >
      0.1 mg kg-1 is permitted.

PMID- 11517722
TI  - Ethyl cellulose polymer microspheres for controlled release of norfluazon.
AB  - The pesticide norfluazon has been microencapsulated using ethyl cellulose to
      develop controlled-release formulations that decrease its mobility through the
      soil and protect it from photodegradation. Ethyl cellulose microspheres loaded
      with norfluazon were prepared by the solvent-evaporation method. To obtain the
      microspheres, certain conditions (pesticide/polymer ratio, percentage of
      emulsifying agent and solvent) were varied. The shape and size of the
      microspheres obtained were studied by scanning electron microscopy. Other
      parameters, such as solids recovery, encapsulation efficiency and pesticide
      loading, were also studied. The release rate of norfluazon from the different
      microspheres was slower than that of pure norfluazon. In particular, microspheres
      obtained with o-xylene, which provided the largest diameter, retarded the initial
      release of the pesticide relative to microspheres obtained with chloroform, or to
      pure norfluazon. Moreover, the studies showed that the pesticide/polymer ratio
      controlled the release of norfluazon, which was slower when this ratio was low.
      Release rates conformed to a generalised kinetic equation for a diffusion
      controlled release mechanism, and the time taken for 50% of the active ingredient
      to be released into water, t50, was calculated.

PMID- 11517723
TI  - Viability and stability of biological control agents on cotton and snap bean
      seeds.
AB  - Cotton and snap bean were selected for a multi-year, multi-state regional (south
      eastern USA) research project to evaluate the efficacy of both commercial and
      experimental bacterial and fungal biological control agents for the management of
      damping-off diseases. The goal for this portion of the project was to determine
      the viability and stability of biological agents after application to seed. The
      biological seed treatments used included: (1) Bacillaceae bacteria, (2) non
      Bacillaceae bacteria, (3) the fungus Trichoderma and (4) the fungus Beauveria
      bassiana. Seed assays were conducted to evaluate the following application
      factors: short-term (< or = 3 months) stability after seed treatment; quality
      (i.e. isolate purity); compatibility with chemical pesticides and other
      biocontrol agents; application uniformity between years and plant species. For
      the bacterial treatments, the Bacillaceae genera (Bacillus and Paenibacillus)
      maintained the greatest population of bacteria per seed, the best viability over
      time and the best application uniformity across years and seed type. The non
      Bacillaceae genera Burkholderia and Pseudomonas had the least viability and
      uniformity. Although Beauveria bassiana was only evaluated one year, the seed
      fungal populations were high and uniform. The seed fungal populations and
      uniformity for the Trichoderma isolates were more variable, except for the
      commercial product T-22. However, this product was contaminated with a
      Streptomyces isolate in both the years that it was evaluated. The study
      demonstrated that Bacillaceae can be mixed with Trichoderma isolates or with
      numerous pesticides to provide an integrated pest control/growth enhancement
      package.

PMID- 11517724
TI  - Synthesis and molluscicidal structure-activity relationships of some novel 1,2,4
      triazole N-methyl carbamates.
AB  - A new series of 1,2,4-triazole derivatives and their corresponding carbamates
      have been synthesized and screened for their molluscicidal activity against two
      types of terrestrial snail, Helix aspersa and Theba pisana, by two methods of
      application, either as contact or as bran baits. Several of the tested compounds
      exhibited good molluscicidal activity, and T pisana was more sensitive than H
      aspersa. Substitution at the o- and/or p-positions of the phenyl ring with
      chlorine or bromine gave higher molluscicidal activity than the unsubstituted
      compound, with o,p-dichloro substitution being optimum. In addition, compounds
      containing two triazole moieties showed higher molluscicidal activity,
      particularly as stomach poisons, than the contact toxic effect of the
      corresponding compound with one triazole ring. In general, carbamate derivatives
      were more active than their corresponding 1,2,4-triazole derivatives.

PMID- 11517725
TI  - Identification of novel inhibitors of calling and in vitro [14C]acetate
      incorporation by pheromone glands of Plodia interpunctella.
AB  - Some octopamine agonists were found to suppress in vitro biosynthesis of the
      calling pheromone of the Indian meal moth, Plodia interpunctella. Isolated
      pheromone-gland preparations incorporated sodium [14C]acetate at a linear rate
      for 3 h when incubated with the pheromone biosynthesis activating neuropeptide
      (PBAN). This incorporation was dependent on the dose of PBAN (up to 0.5 microM).
      Thin-layer chromatography of a pheromone-gland extract revealed quantitative
      incorporation of radioactivity into a product exhibiting the same mobility as
      (Z,E)-9,12-tetradecadienyl acetate, the main component of the calling pheromone
      of P interpunctella. Twenty-seven octopamine agonists were initially screened
      using a calling behaviour bioassay of female P interpunctella. Four derivatives
      with activity in the nanomolar range were identified which were, in order of
      decreasing pheromonostatic activity: 2-(2,6-diethylphenylimino)thiazolidine > 2
      (2,6-diethylphenylimino)oxazolidine > 2-(2,6-dimethylphenylimino)thiazolidine > 2
      (2-ethylphenylimino)oxazolidine. These compounds also showed in vitro inhibitory
      activity in intracellular de novo pheromone biosynthesis. The results of the
      present study indicate that these derivatives could provide useful information in
      the characterization and differentiation of octopaminergic receptor types and
      subtypes.

PMID- 11517726
TI  - Seed treatment with beta-aminobutyric acid protects Pennisetum glaucum
      systemically from Sclerospora graminicola.
AB  - beta-Aminobutyric acid (BABA) treatment of pearl millet [Pennisetum glaucum (L) R
      Br] seeds influenced seedling vigour and protected the seedlings from downy
      mildew disease caused by the oomycetous biotropic fungus Sclerospora graminicola
      (Sacc) Schroet. Of the different concentrations of BABA tested, viz 25, 50, 75
      and 100 mM, seeds treated with 50 mM for 6 h resulted in the maximum of 1428
      seedling vigour and showed 23% disease incidence in comparison with the control
      which recorded a seedling vigour of 1260 and 98% disease incidence i.e. 75%
      protection from disease. Seeds treated with BABA when challenged for downy mildew
      disease using zoospores of S graminicola required 48 h after inducer treatment to
      develop maximum resistance. Durability of induced resistance was also tested in
      plants raised from seeds treated with the inducer and identified as resistant, by
      second challenge inoculation with the downy mildew pathogen at tillers and
      inflorescence axes. Reduced disease incidence of only 10 and 12% in these plants,
      compared with 71 and 76% disease in control plants inoculated at the tillers and
      inflorescence axes, respectively, suggested that resistance induced in seeds with
      BABA remained operative through vegetative and reproductive growth of pearl
      millet plants. Induction of resistance by seed treatment with BABA enhanced
      vegetative growth, viz height, fresh weight, leaf area and tillering, and
      reproductive growth, viz early flowering, number of productive ear heads and 1000
      seed weight. Studies on induction of resistance in different cultivars of pearl
      millet with varying resistance reaction to downy mildew indicated that the
      protection offered by BABA is independent of the nature of cultivars used and not
      dependent on their constitutive resistance.

PMID- 11517727
TI  - Is attract-and-kill technology potent against insecticide-resistant Lepidoptera?
AB  - Attract-and-kill techniques, associating an attractant and a contact insecticide
      in a sticky formulation, are a new way of controlling Lepidopteran pests.
      Insecticide resistance may, however, limit the effectiveness and even the
      attractiveness of such formulations where resistance pleiotropic effects
      influence pheromone perception. We have tested this hypothesis on resistant
      codling moths Cydia pomonella (L) using a commercial formulation containing (E,E)
      8,10-dodecadien-1-ol (codlemone), the major component of the sex pheromone, as an
      attractant and permethrin as toxicant. We first compared the attractiveness of
      codlemone in a wind tunnel and the contact toxicity of pyrethroids on males of
      one susceptible and of three strains selected for resistance to diflubenzuron,
      deltamethrin and azinphos-methyl. The dose-response relationships of males of
      susceptible and resistant strains to codlemone did not differ significantly. The
      deltamethrin-selected strain was the most resistant to pyrethroids, exhibiting
      138-, 25- and 18-fold resistance ratios to deltamethrin, cypermethrin and
      permethrin, respectively. The efficiency of the attracticide formulation, applied
      successively on filter paper support, glass support and wood support, was
      estimated by recording the mortality delay of males after natural contact with
      the formulation in the wind tunnel. The deltamethrin- and diflubenzuron-resistant
      strains were significantly less affected than the susceptible strain by contact
      with the attracticide on the wooden support, exhibiting 58- and 2.3-fold greater
      LT50 ratios, respectively. Mortality of deltamethrin-resistant moths did not
      exceed 40% after 48 h. The LT50 value was significantly greater on filter paper
      support than on the two other supports. Surprisingly, the LT50 ratio of the
      deltamethrin-resistant strain was markedly higher on filter paper support (1021
      fold), which was more absorbent, than on the glass support (31-fold). No
      sublethal effects in terms of pheromone response, mating or fecundity occurred in
      moths surviving contact with the attracticide. Choice of insecticides in
      attracticide formulations will be influenced by the resistance background of the
      target pests. Principles of insecticide resistance management may also be applied
      to attract-and-kill technology by alternating with other insecticides or control
      methods.

PMID- 11517728
TI  - Finite dose diffusion studies: III. Effects of temperature, humidity and deposit
      manipulation on NAA penetration through isolated tomato fruit cuticles.
AB  - Effects of temperature, humidity, rewetting and removal of deposits on
      penetration of NAA [2-(1-naphthyl)acetic acid] through isolated tomato
      (Lycopersicon esculentum Mill) fruit cuticles were studied using a finite dose
      diffusion system. In this system, an aqueous 5-microliter droplet (0.1 mM NAA in
      20 mM citric acid buffer) is applied to the outer surface of a cuticle, which is
      mounted in a glass diffusion half-cell. The cell wall surface is in contact with
      a receiver solution (20 mM citrate). Penetration is monitored by repeated
      sampling of the receiver solution. Droplets appeared dry on visual inspection
      within 1 h of application, but significant NAA penetration continued after
      droplet drying. Maximum rates of NAA penetration increased exponentially as
      temperature was increased (from 5 degrees to 35 degrees C), the energy of
      activation averaging 153 (+/- 11.6)kJ mol-1. At 35 degrees C, penetration reached
      a plateau within 10 h of application (at 91.1 (+/- 1.0)% of dose applied) while
      at 5 degrees C penetration after 800 h reached only 30.2 (+/- 7.5)%. Increasing
      relative humidity from 20 to 80% increased maximum rates [from 1.0 (+/- 0.21) to
      2.7 (+/- 0.80)% h-1] and penetration at 120 h after application [from 36.8 (+/-
      2.1) to 64.3 (+/- 3.7)%]. Rewetting deposits at 120, 240 and 360 h after
      application resulted in increased NAA penetration. However, amounts and rates of
      NAA penetration progressively decreased with each subsequent rewetting. Removal
      of deposits by cellulose acetate stripping at various times after droplet
      application resulted in a rapid decrease in NAA penetration. NAA penetration
      following deposit removal was always less than 6.1% of the amount of NAA applied
      and averaged 0.5 (+/- 0.2)% when deposits were removed immediately after droplet
      drying.

PMID- 11517729
TI  - Resistance of a soybean cell line to oxyfluorfen by overproduction of
      mitochondrial protoporphyrinogen oxidase.
AB  - The diphenyl ether herbicide oxyfluorfen (2-chloro-4-trifluoromethylphenyl 3
      ethoxy-4-nitrophenyl ether) inhibits protoporphyrinogen oxidase (Protox) which
      catalyzes the oxidation of protoporphyrinogen IX (Protogen) to protoporphyrin IX
      (Proto IX), the last step of the common pathway to chlorophyll and haeme
      biosynthesis. We have selected an oxyfluorfen-resistant soybean cell line by
      stepwise selection methods, and the resistance mechanism has been investigated.
      No growth inhibition was observed in resistant cells at a concentration of 10(-7)
      M oxyfluorfen, a concentration at which normal cells did not survive. While the
      degree of inhibition of total extractable Protox by oxyfluorfen was the same in
      both cell types, the enzyme activity in the mitochondrial fraction from non
      treated resistant cells was about nine-fold higher than that from normal cells.
      Northern analysis of mitochondrial Protox revealed that the concentration of
      mitochondrial Protox mRNA was much higher in resistant cells than that in normal
      cells. There were no differences in the absorption and metabolic breakdown of
      oxyfluorfen. The growth of resistant cells was also insensitive to oxadiazon [5
      tert-butyl-3-(2,4-dichloro-5-isopropoxyphenyl)-1,3,4-oxadiazol-2-(3H)- one], the
      other chemical class of Protox inhibitor. Therefore, the resistance of the
      selected soybean cell line to oxyfluorfen is probably mainly due to the
      overproduction of mitochondrial Protox.

PMID- 11517730
TI  - METI-acaricide resistance in Tetranychus urticae does not confer resistance to
      the naphthoquinones.
AB  - The naphthoquinones and the METI group of compounds act on sites associated with
      mitochondrial respiration, but METI-resistant strains of two-spotted spider mite
      from Japan and the UK exhibited no cross-resistance to the naphthoquinones. The
      potential for developing commercial naphthoquinones therefore remains high.

PMID- 11517731
TI  - Viscosity of gruels for infants: a comparison of measurement procedures.
AB  - Numerous studies have been carried out to investigate energy density and
      consistency of gruels for infants in developing countries. However, starch-rich
      gruels have a complex rheological behavior and their consistency is difficult to
      characterize. Many published gruel viscosity data are available, but the lack of
      standardized viscosity measurement procedures makes comparisons and
      interpretations difficult. The influences of viscometer type and viscosity
      measurement conditions on gruels prepared with simple or multicomponent flours
      were assessed in this study. The results showed a drastic decrease in apparent
      viscosity when the shear rate increased. Other factors like shear time and gruel
      temperature also had a marked influence on apparent viscosity. For two types of
      gruel (maize or multicomponent flour) prepared at different concentrations,
      correspondences between a short qualitative description of the consistency and
      apparent viscosity values obtained with several viscometers in different
      measurement conditions are given. Finally, recommendations are put forward on
      techniques to obtain valid data on gruel consistency, adapted to each type of
      study (laboratory, field or large-scale surveys).

PMID- 11517732
TI  - Nutritional status and dietary intakes of children aged 2-5 years and their
      caregivers in a rural South African community.
AB  - The objective of this study was to determine the nutritional status regarding
      vitamin A, iron and anthropometric indices and dietary intakes of children aged 2
      5 years and their caregivers in a rural South African community. Micronutrient,
      haematological, anthropometric and dietary indicators were used to assess
      nutritional status during a cross-sectional survey. The setting was a low
      socioeconomic rural African community (Ndunakazi), approximately 60 km northwest
      of the coastal city of Durban in KwaZulu-Natal, South Africa. The subjects were
      children aged 2-5 years (n = 164), and their caregivers (n = 137). Of the
      preschool children, 50% had a low vitamin A status (serum retinol < 20
      micrograms/dL), 54% were anaemic (Hb < 11 micrograms/dL), 33% had depleted iron
      stores (serum ferritin levels < 10 micrograms/L), and 21% were stunted (Z-score
      for height-for-age < -2SD). Of the caregivers, 30% had a low vitamin A status
      (serum retinol < 30 micrograms/dL), 44% were anaemic (Hb < 11 micrograms/dL), 19%
      had depleted iron stores (serum ferritin levels < 12 micrograms/L), and 40% and
      26% were overweight (BMI > or = 24 and < 30) and obese (BMI > or = 30),
      respectively. The children and caregivers consumed a cereal-based diet, with
      phutu (a stiff porridge made with maize meal), rice and bread as staple foods.
      Quantitative dietary analysis showed that the dietary intakes were high in
      carbohydrates (approximately 70% of total energy), while fat intake was within
      the prudent dietary guideline of 30% of total energy intake. Median dietary
      intakes were below 50% of the RDA for calcium, zinc (children only), vitamin A,
      riboflavin, niacin (children only) and vitamin B12. These preschool children and
      their caregivers consumed a high carbohydrate diet deficient in most of the
      essential micronutrients. The poor quality of the diet was reflected in a poor
      vitamin A and iron status, and one-fifth of the children showed linear growth
      retardation. Nutrition education and intervention programmes should address
      micronutrient deficiencies, with the focus not only on quantity, but also quality
      of the diet.

PMID- 11517733
TI  - Processing of newly released ricebean and fababean cultivars: changes in total
      and available calcium, iron and phosphorus.
AB  - The seeds of newly released high-yielding cultivars of ricebean (RB-32) and
      fababean (VH-82-1) contained good amounts of calcium, phosphorus and iron. Due to
      soaking and sprouting, significant losses occurred in the total mineral content
      due to leaching. However, availability of these minerals improved considerably.
      Sprouting was found to be the best inexpensive processing method, followed by
      dehulling and soaking for enhancing the mineral availability.

PMID- 11517734
TI  - Solubility and relative absorption of copper, iron, and zinc in two milk-based
      liquid infant formulae.
AB  - The relative solubility of copper, iron, and zinc in two experimental liquid
      infant formulae are examined. The results of these trials suggest that
      substituting organic forms of copper and iron in the mix results in an almost
      three-fold increase in their solubility (iron lactate, 73.4% vs ferrous sulfate,
      27.6% and copper gluconate, 11.3% vs cupric sulfate, 3.0%). Organic zinc
      substitutes did not show this pattern of increased solubility Electron microscopy
      was employed to document the changes in protein-protein and protein-lipid
      interactions and to examine the pattern of electron-dense precipitates in the two
      experimental formulae. Electron micrographs of the liquid infant formula that had
      been formulated using inorganic salts (sulfates) showed extensive attachment of
      denatured whey proteins and casein micelles to the oil droplet surfaces and the
      surface of the oil droplets were also punctuated by electron-dense granule. The
      oil droplets of the formula produced using organic versions of the mineral salts
      were smooth and clear of electron-dense deposits. Experiments were designed to
      determine whether the observed changes in solubility and microstructure were
      correlated with increases in relative absorption of the minerals. We applied a
      technique of in vitro acidification followed by a peptic digestion of the two
      experimental infant formulae with human milk samples as controls. Coupling this
      in vitro digestion with an absorption model consisting of live isolated
      intestinal loops from guinea pig we were able to assess the relative absorption
      of copper, iron and zinc in the test digests. The relative absorption of the
      three minerals from digests of human milk was significantly higher than for
      either of the experimental formulae. Relative mineral absorption from digests of
      the two experimental infant formulae tested was only significantly different (P <
      0.05) for Fe. Based on the results from this study we can conclude that
      substituting organic forms of iron in bovine milk-base infant formulae would have
      beneficial effects on both the solubility and bioavailability of this important
      micronutrient.

PMID- 11517735
TI  - Effect of yam (Dioscorea cayenensis) and dasheen (Colocassia esculenta) extracts
      on the kidney of streptozotocin-induced diabetic rats.
AB  - Streptozotocin-induced diabetic wistar rats were maintained for 4 weeks on a
      supplement of extracts of yam (Dioscorea cayenensis) or dasheen (Colocassia
      esculenta). The activities of malic enzyme, NADP+ isocitrate dehydrogenase,
      Glucose 6-P-dehydrogenase and the transaminases were determined to assess any
      degree of metabolic alteration caused by diabetic nephropathy. Diabetic rats fed
      normal diet and those fed yam extract, dasheen extract and commercial linamarin
      respectively lost weight significantly compared to healthy controls. The diabetic
      rats fed dasheen extract, maintained near normoglycaemic values compared to
      diabetic rats on normal diet (P < 0.05). Malic enzyme activity was significantly
      reduced (P < 0.05) in diabetic rats on the normal diet compared to normal healthy
      controls. Feeding of yam or dasheen extract raised the activity of this enzyme
      towards normal. Feeding of dasheen extract or commercial linamarin significantly
      lowered (P < 0.05) the activity of NADP+ isocitrate dehydrogenase below that of
      healthy controls. Glucose 6-P-dehydrogenase activity was significantly increased
      (P < 0.05) in diabetic rats compared to healthy controls. Alanine transaminase in
      the kidney of diabetic rats fed yam extract was significantly higher than healthy
      controls (P < 0.05). These results demonstrate an overall aggravation of the
      diabetic nephropathy by yam and dasheen extracts in the diet. In the Caribbean
      region where these foods are dietary staples, there may be a correlation with the
      reported high prevalence of diabetes mellitus and the development of renal
      disease.

PMID- 11517736
TI  - Trans fatty acids and cholesterol metabolism: mechanistic studies in rats and
      rabbits fed semipurified diets.
AB  - Studies were conducted in rabbits and rats to investigate the effects of diets
      rich in oleic (CIS diet), palmitic (SAT diet) and trans fatty acids (TRANS diet)
      on plasma lipids and lipoprotein metabolism. An important difference between
      these species is that rabbits possess plasma cholesteryl ester transfer protein
      (CETP) activity while rats are devoid of transfer activity. In the presence of
      dietary cholesterol (0.2% w/w) the change in plasma low density lipoprotein
      cholesterol (LDL-C) concentration from baseline was significantly higher in
      rabbits fed the TRANS diet compared with those fed the CIS diet (P < 0.01).
      Despite this difference, the hepatic LDL-receptor activity was similar in all
      groups. Also, the fatty acid composition of hepatic phospholipids was affected by
      diet with lower proportion of palmitic (11%) and higher (19%) linoleic acid
      despite a similar content in the diet. These effects may represent the
      maintenance of membrane fluidity within narrow limits to ensure optimal function.
      The studies in rats showed that the plasma total cholesterol concentration was
      20% lower (P < 0.01) in TRANS-fed rats compared with those fed the CIS diet. The
      results of an in vivo assay of reverse cholesterol transport (RCT) suggested that
      the three diets gave rise to high density lipoprotein (HDL) particles with
      similar capacity to accept cellular cholesterol. The differential effects of
      dietary trans fatty acids in these animal models provide another line of evidence
      that reinforces the significant role of CETP activity in determining the
      distribution of plasma cholesterol in response to dietary trans fatty acids.

PMID- 11517737
TI  - Antioxidant activity and inhibitory effect of Gamazumi (Viburnum dilatatum
      THUNB.) on oxidative damage induced by water immersion restraint stress in rats.
AB  - The antioxidant activity and antiulcer effects of Gamazumi (Viburnum dilatatum
      THUNB.) fruit squeezing solution (GSS) were investigated. GSS including no
      antioxidant additive showed strong antioxidant activity by the XYZ-dish method
      and the electron spin resonance (ESR) method. GSS showed to have no negative
      effect on growth of rats for 2 weeks of feeding with free access to GSS. After
      feeding, the GSS group showed a significant inhibitory effect on gastric ulcer
      formation by water immersion restraint stress for 6 hours compared with the Water
      group. Plasma, liver and stomach concentrations of lipid peroxide in the GSS
      group were reduced rather than the water group. Furthermore, the activities of
      plasma lactic dehydrogenase, amylase and creatine phosphokinase are ordinarily
      increased by stress; however these activities in the GSS group decreased to the
      level in the Control group having no stress. The physiological effects of GSS
      were similar to, or higher than, those of 0.1% (-)-epigallocatechin gallate
      (EGCg) solution. These effects of EGCg and GSS were similar to the order of
      antioxidant activity against hydroxyl radical found by both the XYZ-dish and the
      ESR methods. It was concluded that after ingestion of GSS, during the period of
      strong antioxidant activity in the body, it could prevent stress-induced
      oxidative damage.

PMID- 11517738
TI  - Body size and physical activity levels of adults on Rarotonga, the Cook Islands.
AB  - Few studies of physical activity and energy expenditure have been carried out in
      the Pacific Region. In this study, the physical activity levels (PALs) of adult
      Cook Islanders living a largely modernised lifestyle by age group and occupation
      category were determined by a 3 day activity recall diary method. The period of
      observation included the previous Sunday, as a representative non-working day. A
      volunteer sample of 332 Cook Islanders aged 22 to 86 years was obtained from the
      total adult population of Rarotonga. Older adults are significantly less active
      than younger adults during the working week, but not during the weekend. Males
      are more physically active than females during the working week, but not on
      weekends. The mean weekday PAL of males engaged in traditional subsistence or who
      are unemployed is 1.88, while the mean weekday PAL of females engaged in
      traditional subsistence or who are housewives is 1.69. Male manual workers have a
      weekday PAL of 1.96, while female manual workers have a weekday PAL of 1.67. The
      weekday PAL values for those employed in clerical and administrative work are
      1.82 (males) and 1.64 (females), while values for professionals are 1.76 (males)
      and 1.65 (females). Weekday physical activity is negatively associated with age,
      in nonlinear fashion. The PALs of adult Cook Islanders living a largely
      modernised lifestyle is lower in older age groups but does not vary by occupation
      category.

PMID- 11517739
TI  - [Double-blind trial of the effectiveness of antibodies to interferon-gamma and
      tumor necrosis factor-alpha in rheumatoid arthritis (preliminary results)].
AB  - AIM: Objective evaluation of the effectiveness and tolerance of antibodies to
      interferon-gamma (TNF-gamma) vs those to tumor necrosis factor-alpha (TNF-a) and
      placebo in patients with rheumatoid arthritis (RA). MATERIAL AND METHODS: A
      double blind randomised controlled trial of effectiveness and tolerance of
      anticytokine antibodies was conducted in 30 patients with active RA. The drugs
      were given i.m. for 5 consecutive days. The results were assessed on day 7 and
      28. RESULTS: Antibodies to both cytokines produced a marked therapeutic effect in
      RA, much greater than placebo effect. Improvement by day 7 was achieved in 9, 7
      and 2 patients on anti-TNF-a, anti-INF-g and placebo, respectively. By day 28 in
      8, 8 and 0 patients, respectively. Tolerance of anticytokines was good.
      Significant differences between the results of treatment with anti-INF-g and anti
      TNF-a were not found. CONCLUSION: Administration of antibodies to INF-a proved
      ineffective and well tolerated method in the treatment of severe RA resistant for
      a number of standard basic drugs. Anti-IFN-a holds great promise when used in
      combination with classic antirheumatoid drugs, primarily with methotrexate.

PMID- 11517740
TI  - [Local radiotherapy in combined treatment of rheumatoid arthritis].
AB  - AIM: To study efficiency in rheumatoid arthritis (RA) of local radiotherapy
      methods: radionuclide synovectomy (RS), x-ray therapy (XRT) and local gamma
      therapy (LGT) proposed by the authors. MATERIAL AND METHODS: 175 patients with RA
      received local radiotherapy on the knee joints. The patients were divided into
      three groups comparable by age, sex and disease characteristics receiving RS, XRT
      and LGT. The patients were for the most part women over 45 years with RA
      (duration 5 years and longer), polyarthritis, the disease x-ray stage II,
      moderate activity. RESULTS: RS was most effective of the above methods,
      especially in long-term period. It produces antiinflammatory and
      immunosuppressive action. The new method, LGT, was effective in more than half
      the patients. It is antiinflammatory and immunosuppressive. XRT was the less
      effective of the three methods as it has only nonspecific antiinflammatory
      action. CONCLUSION: Local radiotherapy enhances efficacy of RA treatment. RS and
      LGT produce immunosuppressive and antiinflammatory actions while XRT has only
      antiinflammatory action.

PMID- 11517741
TI  - [Autoantibodies to vasoactive peptides and angiotensin converting enzyme in
      patients with systemic diseases of the connective tissue].
AB  - AIM: To estimate the level of natural autoantibodies (NAAb) to angiotensin
      converting enzyme (ACE) and endogenic mediators affecting vascular tone
      (bradykinin--BK, angiotensin II--AII, vasopressin--VP) as well as the activity of
      serum ACE in patients with systemic diseases of the connective tissue. MATERIAL
      AND METHODS: Levels of NAAb were measured by enzyme immunoassay in sera from 30
      patients with SLE, 19 patients with rheumatoid arthritis (RA) and 36 patients
      with scleroderma systematica (SS). Serum from donors served control. IgM NAAb to
      ACE were measured by a new technique. Serum ACE activity was determined by the
      initial velocity of hydrolysis reaction using spectrofluometry. RESULTS: IgM NAAb
      were detected in the sera of both patients and donors. SS patients had the level
      of NAAb to ACE in diffuse form significantly higher than in limited (p < 0.05).
      In SLE and SS patients ACE activity was significantly lower (p < 0.05) than in
      healthy subjects and RA patients. Levels of NAAb to BK was significantly elevated
      (p < 0.01) in patients with SLE and RA vs donors while to AII in SS patients it
      was lowered (p < 0.001). Patients with diffuse SS had NAAb to BK higher than
      patients with SS limited form (p < 0.01). In SLE the lowest levels of NAAb to all
      the mediators studied were observed in patients with nephritis, for NAAb to VP
      the differences were significant (p < 0.05). In patients with urinary syndrome
      concentration of NAAb to BK was significantly higher (p < 0.01), differences
      between their levels in patients with nephritis and urinary syndrome were also
      significant (p < 0.05). CONCLUSION: Further studies are needed for specification
      of physiological or pathological role of NAAb to endogenic mediators.

PMID- 11517742
TI  - [CNS lupus: problems and achievements (results of a 10-year clinical and
      instrumental study) (lecture)].

PMID- 11517743
TI  - [Myocardial microcirculation in patients with systemic lupus erythematosus].
AB  - AIM: To examine myocardial microcirculation in patients with SLE. MATERIAL AND
      METHODS: Examination of 21 SLE patients consisted of perfusion tomoscintigraphy
      of the myocardium with Tl-201 at rest and in combination with bicycle exercise.
      Various protocols were used. RESULTS: The majority of SLE patients had resting
      disorders of myocardial perfusion: 5 had macrofocal scar lesion of the
      myocardium, 12 had disorders typical for small-focal myocardial fibrosis. Normal
      distribution of the perfusion occurred in 4 cases. Tomoscintigraphy performed in
      combination with exercise test revealed in 11 of 15 patients transient perfusion
      disturbances reflecting transient myocardial ischemia. One third of the patients
      had changes characteristic of myocardial ischemia due to coronary
      atherosclerosis. CONCLUSION: SLE patients have disorders of myocardial perfusion
      including those characteristic of scar lesion, small-focal cardiofibrosis and
      transient myocardial ischemia of different genesis: due to disorders in
      microcirculation and atherosclerotic lesion of major coronary arteries.

PMID- 11517744
TI  - [Echocardiographic functional assessment of the heart and lipid metabolism in
      patients with systemic scleroderma and systemic lupus erythematosus].
AB  - AIM: To characterize structural-functional state of the heart by means of uni-,
      two-dimentional and doppler echocardiography in impulse regimen; to evaluate
      lipid metabolism in patients with scleroderma systematica (SS) and systemic lupus
      erythematosus (SLE). MATERIAL AND METHODS: The examination of 35 SS and 38 SLE
      patients included clinical examination, echocardioscopy with doppler
      cardiography, measurements of serum concentrations of total cholesterol,
      triglycerides, low and high density lipoproteins, atherogenic index. RESULTS: In
      SS patients central hemodynamics reflects hyperdynamics. In intact contractility,
      diastolic function of the ventricles is impaired. Elevated atherogenicity of the
      serum was found in both the groups. CONCLUSION: According to echocardiography SLE
      and SS are associated with changes in both intracardiac and central hemodynamics.
      High atherogenicity of the serum may appear an additional factor of risk of
      hemodynamic disturbances.

PMID- 11517745
TI  - [Multivariate analysis as a method of determination of anthropogenic load on the
      course of Raynaud's disease in patients with systemic scleroderma and systemic
      lupus erythematosus].
AB  - AIM: To determine the effect of high industrial pollution on development of
      Raynaud's syndrome and impairment of pulmonary hemodynamics in patients with
      scleroderma systematica (SS) and systemic lupus erythematosus (SLE). Two groups
      of patients were examined: 20 SS and 33 SLE patients living in highly polluted
      territories, 15 SS and 27 SLE patients living in moderately contaminated
      territories. The tests included capillaroscopy, thermography, rheovasography of
      the fingers, zonal rheopulmonography. Semiquantitative spectral analysis measured
      content of 3 trace elements (Ti, Ba, Li) and 16 heavy metals (Cu, Zn, Pb, Ni, Mn,
      Sn, Cr, Y, Ga, Ag, Mo, Bi, Co, Cd, Fe, Zr) in the patients' hair. RESULTS:
      Patients living in highly polluted areas had a severe course of Raynaud's
      syndrome. Metal accumulation is decisive in patients of group 1; in development
      of staging of Raynaud's syndrome the key role belongs to lead, nickel, tin and
      iron; realization of the factor of the disease activity is related to lowering of
      zinc, copper concentrations and growing concentration of nickel. CONCLUSION:
      Vascular disorders in SS and SLE in patients living in heavily contaminated areas
      aggravate due to direct damage from heavy metals.

PMID- 11517746
TI  - [Features of microcirculatory disorders in acute and recurrent hemorrhagic
      vasculitis (Schonlein-Henoch disease)].
AB  - AIM: To study microcirculatory disturbances in acute and chronic hemorrhagic
      vasculitis (HV). MATERIAL AND METHODS: The examination of 44 HV patients included
      clinical and immunological examinations, conjunctival biomicroscopy, tests for
      blood viscosity, aggregation of erythrocytes, coagulation parameters. In 8
      patients morphological examination of skin microvessels was made (light
      microscopy and electron microscopy). RESULTS: Changes in microcirculation of
      patients with acute HV were characterized by increased IgA and red cell
      aggregation, tendency to hypercoagulation. Morphologically, there was high
      permeability of the microvessels wall. In patients with chronic HV laboratory
      parameters normalized except elevated level of circulating immune complexes and
      red cell aggregation. Morphological picture of microcirculatory disturbances in
      patients with chronic HV was characterized by productive vasculitis. CONCLUSION:
      In HV patients microcirculatory disorders caused by immunologic mechanisms are
      realized through increased permeability of microvessel wall, high aggregation of
      erythrocytes in microvessels and hypercoagulation in acute HV. In patients with
      chronic HV productive vasculitis and high aggregation of erythrocytes are
      registered.

PMID- 11517747
TI  - [Adamantiadi-Behcet syndrome: treatment with recombinant leukocytic interferon].
AB  - AIM: To evaluate efficacy of synthetic leukocytic interferon (SLI) in patients
      with severe Adamantiadi-Behcet syndrome (ABS). MATERIALS AND METHODS: The trial
      enrolled 18 patients (11 men and 7 women aged 25 to 43 years) with severe ABS.
      The duration of the disease ranged from 1 to 12 years. Subcutaneous ABS
      injections in a dose 5 x 10(6) U/m2 for 8 weeks followed by 3 x 10(6) for 16
      weeks. The results were estimated by standard clinical and biochemical indices.
      RESULTS: All 18 patients responded to the treatment. After the course of
      treatment 13 patients were in remission for 4-52 months. The rest of the patients
      were given one more course of treatment.

PMID- 11517748
TI  - [Neuritic bleeding and undiscovered mechanisms of regulation of the hemostasis
      system].

PMID- 11517749
TI  - [Debatable problems of systemic vasculitis].

PMID- 11517750
TI  - [International decade of bone and joint diseases (The Bone and Joint Decade 2000
      2010) -- a multidisciplinary action].

PMID- 11517751
TI  - [Local injection therapy of rheumatoid arthritis].

PMID- 11517752
TI  - [Role of cyclooxygenase-2 (COG-2) in the etiology of pain].

PMID- 11517753
TI  - [Celebrex: confirmed effectiveness and safety (new data)].

PMID- 11517755
TI  - [Gastroduodenal tolerance of celecoxib (celebrex) in patients with
      osteoarthrosis: an endoscopic evaluation].

PMID- 11517754
TI  - [Effectiveness and tolerance of celebrex in osteoarthrosis (data of a Russian
      study)].

PMID- 11517756
TI  - [Department clinics of the Moscow University in the 2d half of the 19th century].

PMID- 11517757
TI  - [Tumor necrosis factor-alpha and kidney damage in rheumatoid arthritis].
AB  - AIM: To investigate clinical significance of tumor necrosis factor-alpha (TNF
      alpha) and kidney damage in patients with rheumatoid arthritis (RA). MATERIAL AND
      METHODS: 94 patients (84 women and 10 men, mean age 45.2 +/- 11.9 years and the
      disease duration 7.5 +/- 6.5 years) with RA and 20 donors were examined. In
      37(39.4%) and 57(60.6%) patients radiological stages I-II and III-IV,
      respectively, were determined. TNF-alpha and C-reactive protein (CRP) were
      measured by ELISA. RESULTS: Serum levels of TNF-alpha in patients with RA
      appeared significantly higher than in donors (10.9 +/- 22.1 pg/ml vs 0.6 +/- 2.0
      pg/ml, p < 0.001). 33 (35.1%) of 94 patients had TNF-alpha levels above 6.6
      pg/ml. High serum levels of TNF-alpha correlated significantly with the presence
      of nephrotic syndrome (r = 0.22, p = 0.03) caused by secondary amyloidosis. There
      were no correlations between high levels of TNF-alpha and sex, age, disease
      duration, stages and clinical activity in patients with RA. Positive correlation
      was found between high levels of TNF-alpha and ESR (r = 0.30, p = 0.003), CRP (r
      = 0.37, p = 0.0001). CONCLUSION: Thus, TNF-alpha may be involved in pathogenesis
      of amyloidosis in RA.

PMID- 11517758
TI  - [The sbr gene product in Drosophila melanogaster and its orthologs in yeast
      (Mex67p) and human (TAP)].
AB  - A DNA sequence from the 9F region of Drosophila melanogaster polytene chromosomes
      was cloned. Sequencing the cloned region and its comparison with the known
      sequences of the D. melanogaster genome showed that the cloned DNA part contains
      gene sbr and adjacent sequences. The literature data on the structure and
      functions of genes TAP in humans and Mex67 in yeast are discussed. These genes
      are orthologous to the sbr gene of Drosophila and control mRNA export from the
      nucleus to the cytoplasm. The literature evidence is consistent with the
      recessive expression of mutation l(1)ts403 (sbr10) upon heat treatment that is
      manifested as impaired HSP synthesis at the posttranscriptional level. However,
      it fails to explain the semidominant effect of the mutation manifested in high
      frequency of meiotic sex-chromosome nondisjunction in heat-treated females. A
      comparison of amino-acid sequences corresponding to the products of the three
      orthologous genes, TAP, Mex67, and sbr, showed that the sbr gene product of
      Drosophila is more similar to the human TAP factor than to the Mex67 factor in
      yeast.

PMID- 11517759
TI  - [KAISO--a new member of the BTB/POZ family specifically bindsto methylated DNA
      sequences].
AB  - A protein specifically binding a symmetrically methylated DNA fragment of the
      first intron of the mts1 gene was studied. The protein was purified by gel
      filtration and affinity chromatography. Mass spectrometry showed that the protein
      is Kaiso, a new member of the BTB/POZ family. To study the association with
      methylated DNA sequences in vivo, the location of Kaiso in NIH 3T3 cells was
      analyzed. Immunofluorescent staining with polyclonal antibodies against Kaiso
      showed that the protein is predominantly associated with the nucleoli. The causes
      of its distribution awaits further investigation. The zinc-finger domains of
      Kaiso were for the first time demonstrated to specifically recognize
      symmetrically methylated DNA sequences in vitro.

PMID- 11517760
TI  - [Transgenic Tobacco plants expressing bacterial genes encoded the thermostable
      glucanases].
AB  - It is shown that bacterial genes for thermostable beta-glucanases are expressed
      retaining their activity and substrate specificity. The leader peptide of the
      carrot extensin exerts effective secretion of the bacterial enzymes into the
      intercellular space of the plant tissue. Expression of the bacterial gene for
      beta-1,3-glucanase in plant tissues alters their morphogenetic potential.
      Regeneration of shoots from the calli of these plant lines requires a six- to
      eightfold increase in cytokinin (6-BAP) concentration in comparison with the
      control lines and the transgenic lines expressing beta-1,3-1,4-glucanase. Rooting
      of transgenic plants expressing the bacterial gene for beta-1,3-glucanase occurs
      much faster. The transgenic plants obtained in the study are proposed as model
      objects for investigating the role of glucanases in plants.

PMID- 11517761
TI  - [Detection of concealed "illegitimate" nuclei in tetrad analysis of the diploid
      progeny of heterokaryons in Saccharomyces cerevisiae].
AB  - In this work, the studies on the previously detected phenomenon of concealed
      heterokaryosis in Saccharomyces cerevisiae were continued. In genetic and
      Southern blotting experiments, one of the nuclei in the heterokaryon was shown to
      be active (capable of division and ensuring the corresponding cell phenotype),
      whereas the other was not expressed until the heterokaryotic clone was
      transferred to the medium selective for this concealed nucleus. Moreover, the
      concealed nucleus was able to assume the active state after fusion with the
      second parental nucleus. It was analyzed whether the nuclei with new marker
      combinations occurring in meiosis can behave as exceptional nuclei. Tetrad
      analysis of hybrids carrying the kar1 mutation in their nuclei revealed the
      relatively high percentage of exceptional tetrads (more than 10%). One spore in
      these tetrads usually formed diploid cells capable of sporulation. The presented
      data of genetic and molecular biological studies testify in favor of the
      assumption that abnormal spores contain two nuclei, which form an "illegitimate"
      hybrid after fusion. An extraneous spore (termed x) has usually a genotype close
      to that of one of the spores in this tetrad. Thus, it was assumed that the
      additional DNA replication round occurs in the absence of cell division during
      one of meiotic divisions. Results of cytological analysis conducted by the method
      of specific DNA staining confirmed the existence of exceptional tetrads, one
      spore of which contains two nuclei.

PMID- 11517762
TI  - [Genetic control of growth and development of yeast Saccharomyces cerevisiae
      cells. Phenotypic selection of mutants among strains of the Peterhof genetic
      collection].
AB  - Results of identifying phenotypes intrinsic to mutations of genes that regulate
      the activity of the signal transduction pathway of RAS-cyclic
      adenosinemonophosphate in six strains belonging to the Peterhof genetic
      collection of the yeast Saccharomyces cerevisiae are presented: an increase or
      decrease in the amount of the accumulated glycogen, resistance or sensitivity to
      heat shock and nitrogen starvation, and the growth and viability in media
      containing unfermentable carbon sources (potassium acetate, ethanol, and
      glycerol) at temperatures 30 and 70 degrees C. Collectively these phenotypic
      characteristics in five examined yeast strains can be interpreted as indicating
      disturbances in the activity of the RAS/cAMP pathway. However, the discrepancies
      revealed between cellular phenotypes in these strains and in the strains with a
      decreased or increased activity of the RAS/cAMP pathway did not allow them to be
      assigned to a particular functional activity group. The inconsistencies between
      phenotypes detected in this study may be prerequisites for the identification of
      new genes responsible for this signal transduction pathway or new mutations in
      the known genes that determine other phenotypic combinations.

PMID- 11517763
TI  - [Effect of gamma-irradiation on oogenesis of Drosophila mutants defective for
      reparation and meiotic recombination].
AB  - Effects of mutations rad201, mei-9, and mei-41 on cell sensitivity to gamma
      radiation in Drosophila oogenesis were studied. Females of the control (Oregon R)
      and mutant strains were irradiated at a dose of 15 Gy. For 9 days after the
      irradiation, the number of eggs in consecutive day batches, the frequency of
      dominant lethals (DLs) among the eggs, and the cytologically recorded
      distribution of oocytes for stages of their development, and the frequency of egg
      chamber degeneration in female ovaries were estimated. As a result of joint
      analysis of the data, different oogenesis stages were characterized with regard
      to the frequency of two radiation-induced events: appearance of DLs in oocytes
      and degeneration of egg chambers due to apoptosis of nurse cells. It was shown
      that the mutations affect these parameters only at particular stages of early
      oogenesis, at which previtellogenetic growth of egg follicles and meiotic
      recombination in oocytes occur. Mutation rad201G1 increased the frequency of DLs
      and egg chamber degeneration, mei-41D5 affected only the DL frequency, and mei
      9a, in addition to enhancing the chamber degeneration frequency, promoted
      radiation "rescue" of some oocytes from the DL induction.

PMID- 11517764
TI  - [Inhibition of gene expression by administration of homologous double-stranded
      RNA in Drosophila melanogaster cell culture].
AB  - Specific inhibition of gene expression by exogenous homologous double-stranded
      RNA (dsRNA) in invertebrates and in the early development of vertebrates is
      termed RNA interference. Cultured cells were cotransfected with reporter plasmids
      and dsRNA. The inhibitor effect on reporter gene expression depended on the
      extent of homology between dsRNA and the target gene. RNA interference was also
      studied in cells cotransfected with plasmids directing synthesis of sense and
      antisense RNAs. Production of antisense RNA only slightly inhibited expression of
      the reporter gene. Simultaneous expression of both sense and antisense RNAs from
      a special plasmid did not inhibit expression of the reporter construct.

PMID- 11517765
TI  - [Inheritance of altered flower morphology and kanamycin resistance in transgenic
      Tobacco plants].
AB  - Inheritance of altered flower morphology and resistance to antibiotic kanamycin
      was studied in the first and second generations (T1 and T2, respectively) of self
      pollinated transgenic tobacco plants. In most transformants, kanamycin resistance
      was closely linked to mutant phenotype. T-DNA-induced mutations were shown to be
      dominant.

PMID- 11517766
TI  - [Geographic variation in color of the synanthropic Blue rock pigeon ].
AB  - Variation in plumage color was studied in 211 populations of the blue rock pigeon
      (Columbia livia) from various geographic zones. The frequency distribution of
      three common and three rare phenotypes and an interspecific hybridization zone of
      C. livia and C. rupestris were described. Different conditions of the origin of
      the urban populations of blue rock pigeon and consequent high genetic
      heterogeneity of this species were revealed. The key aspect of color polymorphism
      in blue rock pigeon is synanthropization, i.e., anthropogenic evolution.

PMID- 11517767
TI  - [Expression of tissue-specific genes with progression of mouse hepatocellular
      carcinoma].
AB  - Expression of hepatocyte-specific genes in slow- and fast-growing hepatocellular
      mouse carcinomas was studied. The fast-growing poorly differentiated passaged
      hepatocarcinoma (fHC) originated from the well-differentiated slow-growing
      variant (sHC). In contrast to the parental hepatocarcinoma, in fHC the expression
      of the hepatocyte nuclear factor 4 (HNF4), in fHC a key factor responsible for
      hepatocyte differentiation, and several HNF-4-responsive genes, such as those for
      transferrin, transthyretin, hepatocyte nuclear factor 1 (HNF1), and serum
      albumin, was significantly suppressed. The expression of exogenous HNF4 in the
      fHC cell culture partially restored the expression of hepatocyte marker genes and
      the appearance of epithelial cell islands in the culture. The described system
      may serve as a convenient model for further analysis of mechanisms underlying
      hepatocarcinogenesis and liver tumor progression.

PMID- 11517768
TI  - [Clinical and molecular cytogenetic analysis of a rare case of mosaicism for
      partial monosomy 3p and partial trisomy 10q in human].
AB  - The results of comprehensive clinical examination and molecular cytogenetic
      analysis of a patient carrying chromosome 3p+ in 69% of the peripheral blood
      lymphocytes are presented. Using microdissection of the metaphase chromosomes
      followed by DOP-PCR, a DNA library specific for the abnormal chromosome was
      obtained. By fluorescence in situ hybridization (FISH) of this DNA library with
      chromosomes from the patient and a healthy donor, the aberrant chromosome was
      identified as der(3)t(3;10)(3p25;q24.3). Since this chromosome was present in
      only a proportion of patient's cells studied and no chromosome aberrations were
      revealed in cells of his parents, the der(3)t(3;10) is suggested to appear de
      novo. The cells carrying der(3)t(3;10) are monosomic for a proportion of 3p25 and
      trisomic for 10q24.3-->qter. The developmental malformations revealed in the
      patient, such as the specific features of facial skeleton, mental retardation,
      microcephaly, and others are similar to those described previously in patients
      with partial 3p monosomy and 10q trisomy.

PMID- 11517769
TI  - [Clinical polymorphism of Shereshevsky-Turner syndrome in Rostov region and
      Northern Caucasus in 1978-1998].
AB  - Polymorphism of Shereshevsky-Turner syndrome (STS) was studied in 233 patients
      who were examined at medical genetic services of the Research Institute of
      Obstetrics and Pediatrics (Rostov-on-Don) and Rostov Regional Hospital from 1978
      to 1998. The subjects examined were residents of the Rostov oblast
      (administrative region) (RO) and some settlements in the northern Caucasus (NC).
      The mean incidence rate of STS was 3.8 per 10,000 newborns in this region in the
      period studied. Most STS cases were accounted for by the X trisomy (60 and 66.6%
      in the RO and NC, respectively). The mosaic form of STS was found in 25% of cases
      in both RO and NC. Other cytogenetic forms were found in 13.5 and 8.33% of
      patients from the RO and NC, respectively. The clinical polymorphism of STS,
      dynamics of its manifestation during ontogeny, and anthropometric parameters of
      the patients were studied. The effects of the age of parents, the season and
      month of conception, occupational hazards at the parents' workplaces, and the
      place of residence on the risk of STS were analyzed. Factor analysis was used to
      determine the sets of the main clinical signs characteristic of different STS
      cytogenetic forms in the RO and NC populations.

PMID- 11517770
TI  - [Effect of genetic background on the ratios between different types of
      dermatoglyphic patterns: recessive genodermatoses].
AB  - The ratios between dermatoglyphic patterns of different types were studied in
      males and females with and without hereditary diseases of the skin. It was found
      that ridge patterns of fingers are determined by special polygenes. Patients with
      monogenic dermatoses (X-linked ichthyosis and autosomal recessive ichthyosiform
      erythroderma) exhibited a suppressed formation of the loop pattern compared to
      control subjects.

PMID- 11517771
TI  - [Analysis of distribution of "mongoloid" haplogroups of mitochondrial DNA among
      indigenous population of the Tuva Republic].
AB  - Variation of Mongoloid-specific restriction sites of mitochondrial genome was
      analyzed in three territorial groups of Tuvinians. Distribution of mitochondrial
      DNA haplogroups A, B, C, and D on the territory of the Tuva Republic was
      estimated. The populations studied did not display distinct differentiation in
      respect to the mtDNA polymorphism. The specific feature of Tuvinian mitochondrial
      gene pool was the prevalence of only one haplogroup C (over 40%), mainly
      represented by two mitotypes. The high frequency of this haplogroup makes
      Tuvinians similar to more northern Siberian populations. On the other hand, the
      presence of haplogroup B indicates that Tuvinians have affinity to ethnic groups
      of Central Asia.

PMID- 11517772
TI  - [Genetic epidemiological study of populations in three regions of Chuvashia
      Republic].
AB  - Comprehensive population genetic and medical genetic studies were performed in
      three raions (districts) of Chuvashia. The population of these districts is more
      than 90% Chuvash. About 70% of the families that completed reproduction had two
      or three children. The proportion of families with four or more children was 18%.
      The duration of generation was 27.6 years. The differential fertility and
      differential mortality indices in the Chuvash population were estimated at 0.33
      and 0.076, respectively. The total index of differential selection was 0.403,
      which is typical of modern urbanized populations. Mean values of local inbreeding
      calculated from Malecot's model of isolation by distance were 0.00124 and 0.00377
      for the urban and rural populations, respectively, of the districts studied. The
      prevalence rates of autosomal dominant (AD), autosomal recessive (AR), and X
      linked diseases were found to be 0.47, 0.52, and 0.35 per 1000, respectively, in
      the urban population and 1.62, 1.14, and 0.31 per 1000, respectively, in the
      rural population. Significant correlation between the local inbreeding and
      prevalence rates of AD and AR diseases was found. A total of 43 AD and 43 AR
      diseases were identified. Some of them were not found in previous studies on
      other populations.

PMID- 11517773
TI  - [Periodic variations of spontaneous chromosome aberration rate in human blood
      lymphocytes ].
AB  - Spontaneous chromosome aberration rate in human blood lymphocytes was studied
      using the data collected during 30 years. Seasonal variation was found. An
      absolute maximum of chromosome aberration rate was observed in winter and a local
      maximum, in summer. In spring and autumn, this value decreased. There was a
      statistically significant trend towards higher frequencies of aberrant metaphases
      during the period studied. A periodic pattern of changes in the chromosome
      aberration frequency was found. The data fitted a sinusoid with a period of 4.5
      years.

PMID- 11517774
TI  - [Study of the DNA primary structure effect on induction of mutations by
      alkylating agents].
AB  - Analysis and comparison of mutation spectra is one of the major tasks of
      molecular biology, since mutation spectra often reveal important properties of
      various mutagens and proteins involved in the repair/replication systems.
      Mutability is known to vary significantly along the nucleotide sequence.
      Mutations are abundant at certain positions (mutation hotspots). In this work, we
      applied regression analysis based on the basic logic patterns to understand the
      role of the nucleotide sequence context in mutation induction. The spectra of
      mutations induced by various alkylating agents were studied. The nucleotide bases
      at positions -2, -1, +1 and +2 were shown to have the most significant effect in
      G:C-->A:T replacements.

PMID- 11517775
TI  - [Drosophila gene rad201 controls cell cycle arrest in irradiated cells].
AB  - Mitotic activity of larval neuroblasts was studied in the wild-type Oregon R and
      mutant rad201G1 and mei-41D5 Drosophila melanogaster at different intervals after
      gamma-irradiation at a dose of 6 Gy. The data obtained suggest that the rad201
      gene is involved in the control of the cell cycle.

PMID- 11517776
TI  - [Current principles of prevention of acute postoperative lesions of the
      gastrointestinal tract].

PMID- 11517777
TI  - [Treatment with veno-sclerosing medications in chronic venous insufficiency].

PMID- 11517778
TI  - [Methodological aspects of surgery of esophageal cancer].
AB  - Based on many years of clinical experiences including more than 400 patients
      operated on for carcinoma of the thoracic portion of the esophagus the author
      describes the methodological aspects of the succession of operation stages and
      rational modes of mobilization of the malignant area guided by the principles of
      observation of the maximum degree of ablastic character of the intervention and
      getting higher radicalism of it.

PMID- 11517779
TI  - [Multiple organ failure].

PMID- 11517780
TI  - [Treatment of gastroduodenal ulcer hemorrhage in middle-aged and aged patients].

PMID- 11517781
TI  - [Preoperative arterial chemoembolization in malignant tumors of the liver].

PMID- 11517782
TI  - [Effects of the dual chamber electrocardiostimulation on the systolic and
      diastolic function of the myocardium].
AB  - An assessment of the indicators of the systolic and diastolic functions of the
      left ventricle was made in 52 patients against the background of
      electrostimulation with a dual chamber electro-cardiostimulator with different
      atrioventricular delays (185, 125 and 79 ms). Different variants of the reactions
      to electrostimulation with a shorter atrioventricular delay were detected: the
      positive dynamics of the diastolic indicators was registered in the hypertrophic
      type of the diastolic dysfunction, aggravation of the diastolic disorders--in the
      restrictive type.

PMID- 11517783
TI  - [Local use of recombinant interleukin-1 beta in the complex treatment of patients
      with acute lung abscess].
AB  - An analysis of results of examination and treatment of 59 patients with a
      prolonged duration of acute abscesses of the lungs has shown the influence of
      immune disorders on the dynamics of the development and outcome of pyo
      destructive disease in the lung. The indications to local immunosubstituting
      therapy were determined. A new original method of administration and a scheme of
      prescription of the medicine Betaleukin are proposed. Clinical efficiency of the
      method proposed is shown. The local immunocorrection used in the complex
      treatment of patients with acute abscesses of the lungs allows to get recovery of
      89% of the patients.

PMID- 11517784
TI  - [Vagotomy in the treatment of acute ulcerations of the stomach complicated by
      severe hemorrhage].
AB  - It has been found that the intramural nerve apparatus of the stomach is involved
      in the mechanism of formation of acute gastroduodenal ulcers. Under stress there
      occurs simultaneous activation of the sympathetic and parasympathetic parts of
      the vegetative nervous system. The released acetylcholine and noradrenaline
      influence the corresponding receptors of the target cells which results in
      hyperproduction of the hydrochloric acid under conditions of hypoxia of the
      gastric wall and promotes acute ulceration. Conservative hemostatic therapy
      allows complete hemostasis to be obtained in 95% of patients with acute
      gastroduodenal ulcers complicated by bleedings. If it fails, the operation of
      choice is thought to be suturing the source of bleeding supplemented with truncal
      vagotomy and pyloroplasty.

PMID- 11517786
TI  - [Emergency surgical treatment of children in hospitals for adults].
AB  - More than 50% of children with urgent surgical diseases are operated upon in
      district hospitals at the units for adults. Insufficient knowledge of
      particularities of surgery and intensive therapy in children of the doctors
      working mainly with adult patients is often responsible for errors and
      complications which often requires to transfer such patients to specialized
      hospitals for children. The author proposes a system of organizing measures based
      on regulation of the district medical prophylactic institutions according to the
      competence of specialists in problems of medicine in children and the equipment
      of the hospital as well as on the division of the patients by their age and
      degree of hemostasis disturbances. An experience with the regulation of surgical
      treatment to children in republic Karelia introduced since 1987 has shown that
      the proposed organization of medical treatment of children in district hospitals
      for adults proved to be effective.

PMID- 11517785
TI  - [Treatment of patients with post-traumatic decompensated ischemia of the limbs].
AB  - The article analyses results of treatment of 48 patients with severe
      posttraumatic decompensated ischemia of extremities. Operations were performed on
      484 patients with injuries of 573 major vessels, 374 of them having traumas of
      the extremity vessels. All the patients were admitted to the hospital with severe
      hemorrhagic and traumatic shock of the III-IV degrees, 58% of them had combined
      traumas. The time from admission to operation was 0.5-24 hours. The "end-to-end"
      anastomoses were applied for the restoration of the vessels and prostheses with
      autovein and homoarterial prosthesis "Homograft" were used. Lethality was 16.7%.
      Reconstruction of the injured artery must be always made after performing
      "stable" osteosynthesis, predominantly with the apparatus of external fixation.
      Early start of active detoxication is of importance. Positive results with saved
      extremities were obtained in 68.8% of the patients. Multiprofile medical
      institutions with a 24-hours regimen of work of different diagnostic and medical
      units can give effective help to patients of this category.

PMID- 11517787
TI  - [A variant of functionally active esophagogastric anastomosis in the surgery of
      stenosing lesions of the esophagus].
AB  - A method of forming a cervical are flux esophgeal-gastric anastomosis has been
      developed allowing to exclude or considerably decrease the effect of esophago
      gastro-pharingeal reflux on the esophageal stump mucosa after subtotal resection
      of the esophagus and performing one-moment esophagogastroplasty. A muscular
      constrictor and a circular invagination valve formed in the area of the
      esophagogastroanastomosis represent a single mechanism having the functional
      properties approximating the natural esophagocardial passage which prevents the
      reflux of the stomach contents into the esophagus stump and is a guarantee of
      prophylactics of reflux-esophagitis and stenosis of the created anastomosis.

PMID- 11517788
TI  - [Plasty of large fixed paraesophageal hernias using polypropylene mesh].
AB  - An experience with treatment of 23 patients with sliding hiatal hernias is
      described, in 3 of them (13%) the hernias were great and fixed. Operations on
      them were performed through a transthoracic access. After bringing the stomach
      down into the abdominal cavity the fundoplication and crurorhaphy with the
      esophageal opening strengthened with a polypropylene net were performed. Long
      tern results were good.

PMID- 11517789
TI  - [Restorative operations in colostomy patients with short stump of the rectum].
AB  - An analysis of restorative operations on 113 patients with a story of obstructive
      resection of the colon after Gartman has shown that of special technical
      difficulty were operations on patients with a short (less than 10 cm) stump of
      the rectum. In 26 patients an apparatus stitch "to the pitch" with the help of
      suturing apparatuses AKA-2 and AKA-4 of the firm "Ethicon" was used. In 9
      patients a combined hand sewing was used. In the patients in whom the continuity
      of the colon was restored with the help of a mechanical suture "to the pitch" or
      by the hand combined sewing there were no incompetent anastomoses. Results of the
      operations were followed-up during the period from 6 months to 3 years. In 2
      patients (5.4%) stricture of the anastomosis was diagnosed following its
      formation with the help of the apparatus AKA-4.

PMID- 11517790
TI  - [Method of dermal autograft in "difficult forms" of inguinal hernia].
AB  - A method of hernioplasty with the help of autodermal transplant thermally treated
      according to the Yanov method was developed in order to lessen the frequency of
      recurrent inguinal hernias. Operations were performed on 168 patients. Among them
      there were 82 patients with direct hernias, 24--with sliding hernias and 62--with
      recurrent hernias. Complications in the operation wound were noted in 1.8% of the
      patients. Long-term results were followed-up in 124 patients. Recurrences were
      found in 2 patients (1.6%).

PMID- 11517791
TI  - [Hemorheological disorders in patients with critical ischemia of the lower limbs
      of atherosclerotic genesis].
AB  - A comparative analysis of hemorheological indices was carried out in 105 patients
      with different variants of the course of critical ischemia of extremities and in
      35 patients with intermittent claudication (as a reference group). Disturbances
      of the rheological properties of blood were revealed in the extremity muscles and
      in 62.4-68.8% of patients with a low functional reserve of the extremity muscles.
      All the examined patients had a low level of total cholesterol against the
      background of dyslipoproteinemia characterized by a decreased level of
      cholesterol of high density lipoprotein with a mild elevation of the
      concentration of cholesterol of low and very low density lipoproteins.

PMID- 11517792
TI  - [Effects of extracorporeal hemo-correction on lipid peroxidation in patients in
      critical states].
AB  - The article presents an analysis of immediate influence of extracorporeal
      hemocorrection upon the indices of lipid peroxidation in resuscitation patients
      of a surgical profile. It was found that hemosorption, ultrafiltration and their
      combination exert a moderate detoxicating effect on lipid peroxidation products.
      The detoxicating effect of plasmapheresis is negligible. Hemosorption and
      ultrafiltration fail to influence the mechanisms of antioxidant defense,
      plasmapheresis eliminates the antioxidant enzymes from blood plasma, and the
      methods of quantum therapy stimulate the activity of superoxide dismutase.

PMID- 11517793
TI  - [Influence of different volumes of infusion therapy on transport and consumption
      of oxygen in the period of shock in patients with severe burns].
AB  - In patients with severe burns during the shock period leading are severe
      disorders of hemodynamics which are the cause of secondary alterations in the
      organs and systems. The main method of treatment of such patients is infusion
      therapy. The approach to determination of the solution volume is ambiguous. A
      comparative analysis of the influence of infusion medium volumes equal to 10% of
      the body mass and calculated by the Parkland formula on transport and consumption
      of oxygen which is the main parameter of the perfusion quality of tissues and
      organs was made in 58 severe burn patients. The results obtained have confirmed
      that severe burn patients mainly have the hypodynamic type of blood circulation
      with altered perfusion of organs and tissues and have shown that the infusion
      therapy calculated by the Parkland formula results in more valuable stabilization
      of the function of transport and consumption of oxygen. So, the parameters of
      blood oxygenation and of oxygen extraction become normalized, metabolic disorders
      and functional instability of the organs disappear in shorter terms.

PMID- 11517794
TI  - [Optimization of indirect electrochemical detoxication in the treatment of
      different endogenous intoxications and multiple organ failure syndrome in
      resuscitation practice].
AB  - The authors have made a statistical analysis of clinical groups of patients in
      the units of resuscitation and intensive therapy of a general profile and of the
      archive materials of a laboratory of extracorporeal hemocorrection. The
      ultraviolet and laser photomodification of autoblood, hemosorption,
      plasmapheresis, ultra- and hemofiltration were used in the complex treatment of
      these patients. In the experimental group there were 190 patients on whom 333
      operations of extracorporeal hemocorrection were made with using indirect
      electrochemical detoxication (IECD). In the control group there were 527 patients
      on whom 1048 analogous operations were made without IECD. The statistical
      processing of the results obtained has shown that IECD method does not have
      immediate detoxicating properties in relation to middle mass molecules and fails
      to substantially influence the processes of lipid peroxidation; sodium
      hypochlorite did not have a deteriorating effect on the clinical-laboratory
      status of patients with severe organic disorders. IECD was shown to potentiate
      the elimination potencies of hemosorption, plasmapheresis, ultra- and
      hemofiltration which resulted in 2.7 times less lethality. The mean bed-day was
      2.8 days shorter, the bed-day in the resuscitation unit--1.2 days shorter.

PMID- 11517795
TI  - [Thermodilution and rheography: the coincidence and reproducibility of results].
AB  - A comparison of the pulmonary artery thermodilution and tetrapolar impedance
      cardiography of cardiac output measurements based on 312 dual determinations has
      shown a good general coincidence, but better reproducibility of the impedance
      cardiography data and more evident character of the errors and artifacts. The
      authors' analysis of the mechanisms and causes of such phenomena is based both on
      their own conclusions and on a wide spectrum of the data of previous
      investigations.

PMID- 11517796
TI  - [Ultrasound examination in the surgery of hepatic echinococcosis].
AB  - It is expedient to perform treatment of patients with the hydatic liver with
      special reference to the stage of the development of the parasite, the state of
      the fibrous capsule which can be established with the help of ultrasound
      examination both before and during the operation. The developed ultrasound
      classification of liver Echinococcosis allows taking into account all the stages
      and forms of the disease which is necessary for planning the optimum method of
      treatment. Using computed tomography and serological methods is justified in the
      situations more complex for diagnosis. In all the cases of exogenous development
      of echinococcal cysts the most radical method is thought to be maximum ablation
      of the fibrous capsule under control of intraoperative ultrasound investigation.

PMID- 11517797
TI  - [A method of surgical treatment of diastasis recti abdominis].
AB  - The author describes her original method of operative treatment of patients with
      diastasis of the rectal muscles of the abdomen intended for liquidation of
      divarication of recti, formation of the new white line and strengthening of
      incompetent aponeurotic formations of the abdominal wall with the help of lavsan
      explants. The method was successfully used in 73 patients with long-standing
      complex diastasis of the rectal muscles of the abdomen. The average age of the
      patients was 45.9 years. The long-term results were followed up during the period
      from 1 to 11 years. No recurrences were noted. Three patients had mild relaxation
      of the lateral muscles of the abdomen, so they have to use elastic bandages and
      to fulfill feasible work.

PMID- 11517798
TI  - [Peritonization of the vermiform process stump in inflammatory infiltration of
      the cecal cupola].
AB  - The article describes the previously proposed technical methods of operation for
      the inflammatory infiltration of the blind gut cupola resulting from destructive
      appendicitis. Their disadvantages are shown. The authors propose to cover the
      blind gut cupola with parietal peritoneum and fix it to the gut with sutures, if
      the infiltration of the blind gut cupola is considerable and it is impossible to
      dip the process stump by a purse-string and Z-shaped suture.

PMID- 11517799
TI  - [Express method of determining blood in the abdominal cavity in closed abdominal
      injuries].
AB  - The article describes an express-method of determining intraabdominal bleeding
      with the help of a benzidine test based on the ability of the hemine group of
      hemoglobin to catalyze the reaction of benzidine oxidation with hydrogen
      peroxide.

PMID- 11517800
TI  - [Effectiveness and safety of catheter ablation of the heart conduction tracts in
      tachyarrhythmia].
AB  - An analysis of 490 operations of radiofrequency catheter destruction in 442
      patients aged from 5 to 83 years has been made. 284 patients (64.3%) had
      congenital and "idiopathic" character of rhythm disturbances. The greater part of
      operations--459 (93.7%)--were performed on patients with supraventricular
      tachycardias, 31 operations (6.3%)--on patients with ventricular arrhythmias.
      Efficacy of operations on patients with congenital diseases of the conducting
      system of the heart was 94.8-100%, frequency of recurrences being 3.3-8%.
      Successful rhythm correction in 78% of patients with atrial flutter was due to
      the risk of appearance of recurrences and development of atrial fibrillation at
      late periods. Creation of atrio-ventricular blockade abolishes tachysystole in
      patients with ciliary arrhythmia, but life quality depends on the adequate system
      of stimulation. The frequency of complications after the catheter destruction is
      associated with the complex character of the intervention and increases when the
      manipulations are to be performed in the left chambers of the heart.

PMID- 11517802
TI  - [Diagnosis and surgical treatment of perforated ulcers of the stomach and
      duodenum].
AB  - An analysis of treatment of 102 patients with perforated ulcers of the stomach
      and duodenum allowed to give a positive estimation of different combinations of
      subsidiary instrumental methods of examination (fibrogastroscopy, laparocentesis,
      fibrogastroscopy + laparocentesis etc.) in diagnosis of the disease. It was noted
      that these methods substantially improve the differential diagnostics and can be
      widely used in clinical practice.

PMID- 11517801
TI  - [Strategy of treatment of patients with acute purulent diseases of the lungs with
      bronchopleural fistulas, pyopneumothorax].
AB  - The authors have made an analysis of their experiences with treatment of 222
      patients with acute pyo-destructive diseases of the lungs, 82 of them had pleural
      complications and bronchopleural fistulas. A conclusion is made that it is
      expedient to use the method of searching occlusion for finding the fistula, the
      optimum terms of obturation in its treatment is determined. In the treatment of
      patients with acute pyo-destructive diseases of the lungs "the active
      conservative strategy" is recommended including active drainage of the
      destruction foci in the lungs and pleural cavity, hermetic sealing of the lung,
      together with detoxicating therapy, making up for protein and electrolyte losses
      with immunomodulation, sanitation of the bronchial tree.

PMID- 11517803
TI  - [Andrei Grigor'evich Savinykh (1888-1963)].

PMID- 11517804
TI  - [Combined treatment of patients with acute cholecystitis complicated by
      choledocholithiasis and mechanical jaundice].
AB  - A scheme of combined treatment was used in 72 patients with a complicated form of
      cholelithiasis. It included retrograde pancreatocholangiography followed by
      endoscopic papillosphincterotomy, intraoperative cholangiography and drainage of
      the common bile duct after Pikovsky. There was not a single case of transition to
      traditional cholecystectomy. Four complications in the postoperative period were
      obviated during relaparoscopy.

PMID- 11517805
TI  - [Results of surgical treatment of patients with external abdominal hernias].
AB  - The vast material concerned with the surgical treatment of patients with external
      abdominal hernias collected for 10 years includes 913 planned operations and 608
      emergency operations for incarcerated hernias. The overall lethality was 3.4%,
      lethality after planned operations being 0.1%, after emergency operations--8.4%.
      It was noted that the amount of elderly and senile patients among patients with
      incarcerated hernias had increased up to 79%. The traditional methods of
      autoplasty were used in 95% of the patients. In 5% of the patients the
      autoabdominal plasty modified by the authors was used for badly amenable to
      treatment inguinal hernias and postoperative ventral hernias. Better results of
      treatment of patients with incarcerated external hernias of the abdomen were due
      to early diagnosis of such hernias, timely hospitalization with special reference
      to the patient's age, correctly performed surgery and prophylactic measures to
      avoid cardiovascular and pulmonary complications at the postoperative period.

PMID- 11517806
TI  - [Hemorrhage from diverticulosis of the colon].
AB  - An experience with treatment of 11 patients with hemorrhage from diverticulosis
      of the colon is presented. The clinical picture, diagnostics and strategy of
      treatment are described.

PMID- 11517807
TI  - [Profuse bleeding caused by angio-digestive fistula].

PMID- 11517808
TI  - New data show only slight drop in use of capitation.

PMID- 11517809
TI  - Change is the only constant expected for US health system.

PMID- 11517810
TI  - City surveys document shift away from risk, into confusion.

PMID- 11517811
TI  - Partners flexes its muscle, boosts fees 25-30% in new long-term contract.

PMID- 11517812
TI  - IHA calls for evolution of California's delegated model.

PMID- 11517813
TI  - Defined contribution redux: a view from the front lines.

PMID- 11517814
TI  - Definity Health shifts risk all the way to the patient; employers attracted to
      'new consumerism'.
AB  - What happens when a company offers its workers a defined contribution health plan
      for the first time? In this case, at least, they flock to it.

PMID- 11517815
TI  - Cholesterol: precursor to many lipid disorders.
AB  - Despite advances in treatment and prevention, coronary heart disease (CHD)
      remains the leading cause of death in the United States. A major risk factor for
      CHD is elevated low-density lipoprotein cholesterol (LDL-C). Randomized clinical
      trials have proven that lowering LDL-C to near target levels significantly
      reduces CHD risk. More aggressive LDL-C reductions would have an even greater
      impact on reducing CHD risk if these goal levels were applied to all patients at
      risk, as identified by a CHD risk prediction scoring system. In 1993 the second
      Adult Treatment Panel (ATP II) of the National Cholesterol Education Program
      issued guidelines that defined CHD risk on the basis of whether a patient
      qualified for primary or secondary prevention. The ATP III guidelines, issued May
      2001, introduce the concept of CHD-equivalent risk in patients without known CHD,
      thereby expanding considerably the number of people eligible for lipid-lowering
      therapy. Unfortunately, many patients who are eligible for therapy are not
      receiving it, and among those on lipid-lowering therapy, less than half have
      achieved their treatment goals. As mentioned, findings from several large-scale
      primary- and secondary-prevention trials with statins and other lipid-lowering
      agents have shown that lowering LDL-C reduces the risk for fatal and nonfatal
      coronary events and results in fewer hospitalizations and revascularization
      procedures. In fact, a review of the 5 major statin trials reveals that the
      higher the patient's baseline CHD risk, the more striking the benefits of therapy
      are. Clearly, the need to lower LDL-C levels is crucial. Meeting this need
      involves targeting patients who are at risk, implementing appropriate treatment,
      and ensuring compliance with therapy.

PMID- 11517816
TI  - Lipid management: tools for getting to the goal.
AB  - The treatment of hypercholesterolemia in the United States begins with the
      recognition of elevated low-density lipoprotein cholesterol (LDL-C) as the
      primary target. An optimal LDL-C level has been defined as < 100 mg/dL. The first
      step in lowering LDL-C continues to be lifestyle modification, which includes a
      restriction of saturated fat and cholesterol, increased physical activity, and
      weight loss, if applicable. Approximately half of all patients with elevated LDL
      C levels will ultimately need treatment with a lipid-lowering drug to achieve
      treatment goals. The preferred drug for first-line treatment in most patients is
      a statin; a bile acid resin or niacin can be used in patients who cannot tolerate
      statins or who are not candidates for stain therapy. Combination therapy is an
      option, with several combinations showing efficacy in lowering LDL-C (statin plus
      bile acid resin, niacin plus bile acid resin) and in lowering both LDL-C and
      triglycerides (statin plus fibrate, statin plus niacin, bile acid resin plus
      niacin). Successful lipid management includes treating to reach the LDL-C goal
      level, treating to reach the non-high-density lipoprotein cholesterol goal level
      if applicable, and managing other risk factors for coronary heart disease.

PMID- 11517817
TI  - Identifying all suspects: case studies.
AB  - Case presentations are one of the most instructive formats for learning. They
      allow the healthcare practitioner to identify and discuss patients who are at
      risk for a disease and then discuss appropriate therapy. Two patients who have
      dyslipidemia and are at risk for a coronary event are described here, along with
      treatment goals and options, audience responses, and discussions of appropriate
      therapy choices. Both patients require aggressive lipid management. One has had
      an angioplasty with placement of a stent. His case is an example of a patient at
      risk for a secondary coronary event; we refer to these cases as secondary
      prevention patients. The other patient has high blood pressure and type 2
      diabetes; her risk for a future coronary event based on Framingham risk data is
      greater than 20% in 10 years and therefore her risk for a future coronary event
      is equal to someone with established coronary heart disease (CHD). Her case is an
      example of what we refer to as a primary-prevention patient at high risk. Several
      large-scale primary- and secondary-prevention trials have demonstrated that
      aggressive lipid management can reduce the risk of future coronary events. In
      this supplement, we review some of those trials, the new guidelines, the concept
      of CHD-equivalent risk, and we will discuss the Framingham risk scoring system to
      predict the 10-year risk of coronary events in individual patients.

PMID- 11517818
TI  - Update on adult immunization.

PMID- 11517819
TI  - PAs gather in Orange County to celebrate the profession and sharpen skills.

PMID- 11517820
TI  - Effective screening for Alzheimer's disease in everyday practice.

PMID- 11517821
TI  - Managing a rare cause of death in infectious mononucleosis.

PMID- 11517822
TI  - Identifying and treating substance abuse.

PMID- 11517823
TI  - Your academy: robust and responsive.

PMID- 11517824
TI  - Intermittent androgen deprivation (IAD) in patients with localized prostate
      cancer and a biochemical progression after radical prostatectomy.
AB  - BACKGROUND: To analyze the modifications in serum PSA levels during IAD in
      patients with an initial PSA progression after radical retropubic prostatectomy
      (RRP). METHODS: Between February 1994 and May 1996, 34 consecutive patients with
      an initial PSA progression (> 0.4 ng/ml) after RRP were selected. All men had
      localized adenocarcinoma of the prostate, stage pT2 pN0 M0. Patients were offered
      IAD when PSA progressed over 0.4 ng/ml. The initial treatment period with
      complete androgen deprivation (CAD) lasted 24 weeks in all cases. After, an
      acceptable nadir PSA level was considered to be a value < or = 0.4 ng/ml. CAD was
      then with held until serum PSA increased to a value over 0.4 ng/ml. RESULTS:
      Follow-up ranges from 144 to 228 weeks. The median time for the first 5 treatment
      cycles was 32, 24, 28, 32 and 32 weeks respectively, with a median time "off"
      therapy that increased from 8 weeks (first cycle) to 22 weeks (fifth cycle). The
      median nadir PSA value during "on" treatment period was 0.20 ng/ml in all 5
      cycles. So far, in none of the patients did a serum PSA fail to decrease during
      "on" treatment period. CONCLUSIONS: We suggest that IAD may be an effective
      therapy in patients with an initial PSA progression after RRP. However, large
      prospective studies are needed to confirm these results and to better understand
      the meaning of PSA variations.

PMID- 11517825
TI  - [Metabolic effects of changes in dietary sodium intake in patients with essential
      hypertension].
AB  - BACKGROUND: To evaluate the metabolic effects of modification of sodium intake in
      patients with essential hypertension. METHODS: Thirteen patients with essential
      hypertension (10 M, median age 51 yrs, range 21-64) followed in random order a
      low-sodium and a high-sodium diet (50 mmol Na/day vs 250 mmol/day for two weeks
      each). At the end of each diet an evaluation was made of 24 hour blood pressure
      (ABPM, Spacelabs 90207) and serum concentration of: glucose, total and HDL
      cholesterol, uric acid, lipoproteins A, B, Lp(a), total proteins, albumin.
      RESULTS: Twenty-four hours systolic and diastolic BP were significantly higher at
      the end of high sodium diet than of low sodium diet [respectively 132 mmHg (120
      161) vs 128 mmHg (109-150); p = 0.008 and 84 mmHg (71-99) vs 81 mmHg (70-95); p =
      0.008)]. No significant variations were found as regards serum glucose and
      lipidic parameters between low and high sodium diets. Serum uric acid was
      significantly higher following low sodium diet [5.9 mg/dl (4.5-8) vs 4.6 mg/dl
      (3.4-6.5); p = 0.003)], as well as serum total proteins [7.2 g/dl (6.9-8.2) vs 7
      g/dl (6.5-7.8); p = 0.027)]. A significant direct correlation was found between
      changes of uric acid and total proteins from low to high sodium diet (Spearman's
      rho = 0.57; p = 0.04). CONCLUSIONS: In patients with essential hypertension a
      moderate dietary sodium restriction, able to reduce significantly 24 hours
      arterial pressure, does not worsen serum glucose nor lipids concentration.

PMID- 11517826
TI  - [Endourologic treatment of transitional cell carcinoma of the upper urinary
      tract].
AB  - Nephrourete-rectomy with excision of a bladder cuff has been the standard
      treatment of the upper urinary tract transitional cell carcinoma. The very
      indolent behavior (GI, II, Ta, T1) of more than 50% and up to 82% of the upper
      urinary tract tumors treated with nephroureterectomy in different series in
      conjunction with the advent of sophisticated endourological techniques have
      permitted in certain cases alternative treatments using a conservative approach
      with either ureteropyeloscopy or percutaneous access. Ureteroscopy is reserved
      for ureteral tumors and small, simple tumors of the renal pelvis (< 1.5 cm) while
      large or multiple tumors of the renal pelvis are approached in a percutaneous
      way. During 14 years 64 patients with transitional cell carcinoma of the upper
      urinary tract were treated percutaneously at our department at Long Island Jewish
      Medical Center, 15 (23.5%) with grade I, 26 (40.6%) with grade II and 23 (35.9%)
      with grade III and IV. After a mean follow-up of 51 months, percutaneously
      treated patients had a tumor specific survival of 85.6%, being 100% for GI
      tumors, 96.1% for GII and 60.8% for GIII. Recurrence of grade I tumors were
      observed in 20%, 26.9% for grade II and 56.5% for Grade III. In conclusion, with
      a rigorous follow-up transitional cell carcinoma of the upper tract with low and
      moderate grades (GI, GII, Ta, T1) can be treated endorologically even in the
      presence of a normal contralateral kidney with low morbility and a long term
      efficiency comparable to a nephroureterectomy. An elective endorologic management
      for GIII tumors is not recommended. Endoscopic conservative surgery can be
      offered when the criteria of good prognosis are found for Ta (such as absence of
      carcinoma in situ, presence of diploidy, low p53 expression and a single tumor)
      and in the cases of a solitary kidney or chronic renal insufficiency or for poor
      surgical candidates for T1. Patients with stage T2-T3 should be offered a
      nephroureterectomy.

PMID- 11517827
TI  - Bizarre leiomyoma of the epididymis. A case report.
AB  - A case of epididymal leiomyoma with bizarre nuclei is described. A 48-year-old
      man presented with a painless scrotal mass raising the suspicion of a testicular
      neoplasm. A seven-year follow-up revealed no evidence of local recurrence or
      distant metastasis. To personal knowledge, this is the first reported case of
      bizarre leiomyoma of the epididymis.

PMID- 11517828
TI  - [Unusual case of mesothelioma of the tunica vaginalis associated with prostatic
      adenocarcinoma].
AB  - Malignant mesothelioma of the tunica vaginalis testis, is a very rare neoplasm
      with highly aggressive biological behaviour. It usually occurs in patients aged
      between 55 and 75 years. A testicular mass is always observed, often accompanied
      with hydrocele. The response to chemotherapy and radiotherapy is poor. Initial
      aggressive surgery is necessary. The median survival, without surgical treatment
      is 23 months. A rare case of malignant mesothelioma of the tunica vaginalis
      testis, observed in a patient affected by prostate neoplasm is reported. A
      radical retropubic prostatectomy was performed. The patient was suffering from
      dysuria and there was a suspect area at the digital examination. Rectal
      ultrasonography and biopsy showed an adenocarcinoma at T1c clinical stage. A
      radical prostatectomy was carried out and histology showed an adenocarcinoma,
      Gleason score 7 pT3bN0M0. Surgery was followed by radiation therapy. After three
      years, a pleural seroma, a cutaneous mass and testicular nodule were observed and
      cytological examination showed endothelial cells. Scrotal orchiectomy was
      performed, because he was suffering from emphysema. Cytological examination
      confirmed malignant mesothelioma of the tunica vaginalis testis. Only 73 cases of
      this tumour have been reported in the last 30 years. The therapeutic options for
      this aggressive neoplasm are discussed. Since chemotherapy and radiation therapy
      had poor results, a rapid surgical treatment, by radical orchiectomy, is
      important.

PMID- 11517829
TI  - [Spontaneous renal hematoma. Report of 4 cases].
AB  - Spontaneous renal and perirenal hematomas are heavy clinical events and, even if
      rare, they need an early diagnosis in order to plan therapy. A spontaneous renal
      hematoma should be suspected in case of acute lumbar pain because in more than
      60% of cases it is due to a neoplastic lesion. In the other cases it is due to
      vascular and infectious kidney diseases while in 5 to 15% of cases the cause of
      the hematoma can not be found. In this paper 4 cases of spontaneous renal
      hematomas quite interesting both for their rarity and the imaging features are
      reported. All cases have been treated by medical therapy. According to personal
      experience and to the literature reports, the primary imaging diagnostic methods
      are ultrasonography and CT, while renal angiography should be employed when a
      vascular disease is suspected. In fact, US can provide the diagnosis of
      spontaneous renal hematoma but only CT can accurately assess its extension and
      moreover detect the cause of the hemorrhage. In personal experience, MR did not
      add significative diagnostic information if compared with CT.

PMID- 11517830
TI  - [Pseudosarcoma of the urinary bladder. Report of a case].
AB  - A case of myofibroblastic pseudosarcomatous tumor of the bladder occurred in a
      patient previously submitted to TURB is reported. Aim of this investigation is to
      demonstrate, on the basis of the literature, the importance of histopathology in
      the diagnosis of bladder pseudosarcoma, since endoscopical and radiological
      methods can erroneously show a neoplasm. A 65-year-old male patient with
      hematuria, submitted to ultrasonography and cystoscopy, revealed a bladder
      superficial papillary formation. A TURB was performed and the histological study
      showed a superficial bladder cancer (T1-G1-2). After a second hematuria episode
      with stranguria a new bladder formation was diagnosed and resected; the
      histological study revealed a bladder pseudosarcoma. The absolute benignity of
      the lesion and the slight difference in the symptomatology between urothelial
      carcinoma and pseudosarcoma are underlined. Furthermore, the importance of
      histopathology to obtain an accurate diagnosis is stressed. The difficulty of a
      preoperative diagnosis without histopathological examination is pointed out.

PMID- 11517831
TI  - [Residual ovarian syndrome with ureteral stenosis].
AB  - The development of a cystic pelvic mass after hysterectomy with preservation of
      ovaries can be the cause of chronic pelvic pain. This entity is called "the
      residual ovary syndrome". To our knowledge there are no cases reported in the
      literature with associated ureteral obstruction. A case in which the formation of
      the pelvic mass contributed at least to the formation of the ureteral stenosis is
      presented. The pelvic pain and stenosis resolved after treatment with GnRH
      analogues and with temporary ureteral stent.

PMID- 11517832
TI  - [Male cervico-urethral obstruction of organic cause: transrectal prostatic
      ultrasonography versus permicturition and urethral ultrasonography].
AB  - AIM: This paper reports personal experience relating to the use of "static" and
      "permicturition" prostatic transrectal ultrasonography and urethral
      ultrasonography in the imaging diagnosis of obstructed patients. METHODS: Between
      January 1996 and January 1998 we selected 96 consecutive patients aged between 25
      and 73 years old (mean 54 years) with symptoms of obstructive dysuria with
      pathological uroflowmetry and pressure/flow rates (Qmax ranging between 5-12
      ml/sec and URA between 34-81). Eighteen of the patients selected had previously
      undergone prostate surgery for benign pathologies. All patients underwent a
      standard and permicturition transrectal ultrasonography and urethral
      ultrasonography using a retrograde approach. The results were compared with those
      obtained by retrograde urethrocystography and urethrocystoscopy, regarded as the
      "gold standard" for the diagnosis of urethral obstruction. RESULTS: Sixty-three
      (65.5%) patients were able to execute the permicturition phase, but only 54
      (56.2%) reported that the test was indicative of "real urination", whereas
      retrograde urethral ultrasonography was well tolerated in all cases and easy to
      accomplish. In 19 (20%) patients (6 of whom had undergone prostate surgery and 13
      were suffering from urethral stenosis), "major" organic alterations responsible
      for urethral obstruction were observed with the combined use of these
      ultrasonographic methods. These were not evident using static transrectal
      ultrasonography and increased the diagnostic sensitivity from 80 to 98%.
      CONCLUSIONS: We feel that an increasingly complete ultrasonographic study of the
      lower urinary tract is necessary, above all in obstructed patients. This can be
      achieved using permicturition and urethral transrectal ultrasonography, ensuring
      an accurate diagnosis and optimising health expenditure.

PMID- 11517833
TI  - Stats and facts. The challenge of inadequate health literacy.

PMID- 11517834
TI  - An owner's reflection on the media, Medicare, and managed care.

PMID- 11517836
TI  - Acronyms abound, computerized patient records do not.

PMID- 11517835
TI  - Allergic rhinitis and wellness opportunities.
AB  - Allergic rhinitis affects one in 10 adult workers and results in substantial
      costs to employers in terms of health care and reduced worker productivity. In
      this article, the author describes many employer-based initiatives, which
      complement professional interventions.

PMID- 11517837
TI  - The utilization management--Internet interface.
AB  - The era of utilization management, in which each physician treatment decision is
      closely scrutinized, is quickly coming to an end. As utilization management
      begins to take a back seat to better cost consciousness in many health plans,
      executives will begin viewing the Internet as the avenue through which
      traditional utilization management changes.

PMID- 11517838
TI  - Pharmacoeconomics in managed care pharmacy.

PMID- 11517839
TI  - Evaluating the role of bias in pharmacoeconomic studies.
AB  - Pharmacoeconomic research is conducted to provide patients, physicians,
      institutional providers, health benefit plan decision makers, and government
      authorities with information about the economic value of pharmaceuticals. Valid
      and appropriate pharmacoeconomic data are vital to informed decision making.
      Methodological guidelines have been proposed for the conduct of pharmacoeconomic
      research to foster high quality and minimize bias. This article outlines the
      types of bias that are introduced in pharmacoeconomic studies using a traditional
      epidemiological approach.

PMID- 11517840
TI  - Risk sharing and prescription product "guarantees".

PMID- 11517841
TI  - Costs and resources associated with the treatment of overactive bladder using
      retrospective medical care claims data.
AB  - The objectives of this study were to determine age- and gender-specific drug
      treatment prevalence rates for overactive bladder (OAB), and to compare resource
      use and costs among MCO members receiving drug treatment for OAB. Administrative
      claims data from seven affiliated health plans were analyzed for 8,661 members
      with a diagnosis or treatment indicative of OAB during 1998. Resource use and
      associated costs were analyzed over a four-month follow-up. In 1998, the
      prevalence of OAB among plan members was 1.1%. Of the patients with OAB, 71% did
      not receive pharmacotherapy. After multivariate analysis, treatment with
      tolterodine, oxybutynin, or other OAB treatment did not significantly affect the
      percent change in total per patient per month (PPPM) costs compared with the
      group not receiving a pharmacologic agent. Although the adjusted percent change
      in PPPM pharmacy costs was significantly higher within the tolterodine group,
      medical and total PPPM costs were not.

PMID- 11517842
TI  - Developing visual aids to enhance presentations.

PMID- 11517843
TI  - Risk assessment of first-degree relatives of women with breast cancer: a
      feasibility study.
AB  - PURPOSE/OBJECTIVES: To measure psychological distress and test the feasibility of
      a psychological intervention to reduce distress in patients undergoing risk
      assessment. DESIGN: Descriptive. SETTING: A comprehensive cancer center located
      in the southeastern United States. SAMPLE: 20 first-degree relatives of women
      diagnosed with breast cancer (X age = 42; range = 21-70) completed the risk
      assessment process. Three were lost to follow-up at three months, leaving a total
      of 17 evaluable patients. METHODS: Data collection was by means of family/medical
      history forms and questionnaires administered at baseline and one and three
      months. Participants were randomized to either a control group consisting of
      standard education about risk for breast cancer or to an intervention group
      consisting of standard education plus a psychological intervention designed to
      teach stress-management skills. MAIN RESEARCH VARIABLES: Psychological distress,
      depressive symptoms, intrusive thoughts about breast cancer, and perceived risk
      for developing breast cancer. FINDINGS: Delivery of a psychological intervention
      proved feasible. Although no statistically significant differences existed
      between the intervention and control groups on distress and depressive symptoms,
      the intervention group reported fewer intrusive thoughts about breast cancer at
      follow-up. Risk did not predict anxiety levels. A large majority (73%) of the
      women overestimated the risk of breast cancer at baseline. CONCLUSIONS: This
      study demonstrated the feasibility of a multidisciplinary team approach to breast
      cancer risk assessment and counseling and management of psychological distress in
      first-degree relatives of women with breast cancer. The data suggest that a
      psychological intervention may reduce cancer-specific psychological distress in
      women at increased risk for breast cancer. IMPLICATIONS FOR NURSING PRACTICE:
      Oncology nurses can play an important role in the delivery of interventions to
      educate and reduce distress in women undergoing breast cancer risk assessment.

PMID- 11517844
TI  - Quality of life and patterns of nontraditional therapy use by patients with
      cancer.
AB  - PURPOSE/OBJECTIVES: To describe the characteristics of patients with cancer that
      may be associated with use of or interest in nontraditional healthcare practices
      or therapies. DESIGN: Descriptive study using survey methodology with a large
      convenience sample. SETTING: Private, outpatient, adult hematology/oncology
      practice in the midwestern United States. SAMPLE: 89 outpatients who had
      received, were currently receiving, or were scheduled to receive chemotherapy for
      cancer. Participants ranged in age from 21-88 years (X = 63.26), were
      predominately Caucasian and female, and had a high school education. METHODS:
      Patients presenting for treatment were handed surveys and asked to mail them back
      to the investigators. Instruments included Ferrans and Powers' Quality of Life
      (QOL) Index--Cancer Version and a questionnaire designed for the purpose of this
      study to obtain demographic information and information regarding interest in or
      use of nontraditional therapy (NT). Data were analyzed for frequency of use,
      interest in using NT, and relationship between use/interest and quality of life.
      MAIN RESEARCH VARIABLES: QOL, using NT. FINDINGS: 34 (39.5%) of the respondents
      initiated use of NT after receiving a diagnosis of cancer; they were more
      commonly female, less than 65 years of age, and more highly educated. New users
      of NT tended to have known about their diagnosis longer, had experienced a
      recurrence or metastasis, and had been told that the possibility of cure was
      unlikely. QOL scores were higher among new users versus continuous users of
      various individual categories of NT. CONCLUSIONS: Adult patients with cancer in
      this study sample very commonly used nontraditional healthcare practices; more
      than one-third initiated their use after diagnosis. IMPLICATIONS FOR NURSING
      PRACTICE: Practitioners are challenged and encouraged to become more
      knowledgeable regarding NT therapy use and more sensitive to issues surrounding
      patients' decisions to use them.

PMID- 11517845
TI  - The process of clinical trials: a model for successful clinical trial
      participation.
AB  - PURPOSE/OBJECTIVES: To present barriers and strategies related to successful
      clinical trial participation and integrate them into a model for successful trial
      participation. DATA SOURCES: The proposed model was developed based on a
      literature review related to clinical trial participation, review of empirical
      studies related to clinical trials, and experiences with subject participation.
      DATA SYNTHESIS: Successful clinical trial participation depends on study design,
      participant factors, issues related to ethnic diversity, the informed consent
      process, and physician factors. CONCLUSIONS: Clinical trial participation is
      critical for all disciplines. However, nurses either are researchers or co
      investigators with physicians on clinical trials, and it is critical for them to
      understand specific barriers and success strategies for patient participation.
      Future studies need to be conducted related to participation in nursing clinical
      trial research. These study results will facilitate successful nursing clinical
      trials. IMPLICATIONS FOR NURSING PRACTICE: This model can be used in
      implementation of clinical trials across disciplines prior to and during
      enrollment of patients into studies.

PMID- 11517846
TI  - Outcome expectancy and success with cognitive-behavioral interventions: the case
      of guided imagery.
AB  - PURPOSE/OBJECTIVES: To describe the role of outcome expectancy in the use of
      cognitive-behavioral interventions and to test three variables (history of
      imagery use, preferred coping style, and perceived credibility of the imagery
      provider) as predictors of outcome expectancy regarding guided imagery. DESIGN:
      Secondary analysis using a descriptive, correlational design. SETTING: Surgery
      clinics at a large, midwestern university hospital. SAMPLE: 75 women undergoing
      surgery for gynecologic or breast cancers. METHODS: Data were collected as part
      of an ongoing trial of guided imagery. Participants completed measures of outcome
      expectancy and predictor variables at a preoperative clinic visit. MAIN RESEARCH
      VARIABLES: Outcome expectancy regarding a guided imagery intervention, previous
      history with imagery, preferred coping style, and perceived credibility of the
      imagery provider. FINDINGS: Significant relationships were demonstrated between
      previous history of imagery use and outcome expectancy (r = 0.47, p < 0.01) and
      between perceived credibility of the imagery provider and outcome expectancy (r =
      0.45, p < 0.05). Preferred coping style was not related to outcome expectancy in
      this sample. Psychometric properties of new instruments were satisfactory.
      CONCLUSIONS: Previous history of imagery use and perceived credibility of the
      imagery provider were supported as predictors of outcome expectancy. Future
      research will be necessary to reexamine the predictive role of preferred coping
      style. IMPLICATIONS FOR NURSING PRACTICE: Nurses should be aware of the potential
      role of outcome expectancy in effectiveness of nursing interventions. Patients'
      previous use of cognitive-behavioral interventions and perceptions of credibility
      may be helpful in selecting appropriate strategies.

PMID- 11517847
TI  - Cancer-related patient education: an overview of the last decade of evaluation
      and research.
AB  - PURPOSE/OBJECTIVES: To provide an overview of cancer-related patient-education
      research to determine future research needs. DATA SOURCES: A literature search of
      peer-reviewed articles from 1989-1999. Databases that were searched included
      Medline, CINAHL, HealthStar, ERIC, CancerLit, and PubMed. DATA SYNTHESIS: 176
      articles were analyzed and synthesized into narrative form. CONCLUSIONS: Patients
      with cancer want and benefit from information, especially when making treatment
      decisions. Education helps patients manage side effects and improves adherence.
      Literacy is an important factor in materials development. The efficacy of
      computer-assisted learning, audio and video programs, and telephone interventions
      is supported in a variety of patient groups. Pain education can improve pain
      control, but the impact on fatigue has not been well researched. IMPLICATIONS FOR
      NURSING PRACTICE: Patient education is an important component of nursing care.
      Research has confirmed its impact in many areas but questions still remain.

PMID- 11517848
TI  - Improving depressive symptoms among caregivers of patients with cancer: results
      of a randomized clinical trial.
AB  - PURPOSE/OBJECTIVES: Determine the impact of a 16-week supportive nursing
      intervention on caregivers of patients with newly diagnosed cancer. DESIGN:
      Randomized clinical trial. SETTING: Two midwestern cancer treatment sites.
      SAMPLE: Caregivers of newly diagnosed patients. Patients' mean age was 55.73
      years; 55% had breast cancer, and 76% were female. Caregivers' mean age was 52.44
      years, and 50% were female. 125 dyads consented to participate; 89 dyads
      completed the study. METHODS: A nursing intervention was delivered to the
      experimental group that emphasized symptom monitoring/management, education,
      emotional support, coordination of services, and caregiver preparation to care.
      Nurses made a total of nine contacts, five in person and four by telephone, over
      16 weeks. Centers for Epidemiological Studies-Depression (CES-D) and a symptom
      inventory were used. Medical record audits were conducted retrospectively. MAIN
      RESEARCH VARIABLES: Patient and caregiver depression scores and patient symptom
      experience. FINDINGS: Baseline caregiver depression and the number of patient
      symptoms at baseline, 9, and 24 weeks were significant predictors of caregiver
      depression at 9 and 24 weeks. However, no main effect of the experimental
      condition existed on caregiver depression. At the final observation, a
      nonsignificant inverse relationship was found between the number of interventions
      and depression scores for caregivers. CONCLUSIONS: The intervention appeared to
      be more effective in slowing the rate of deterioration of depressive symptoms
      than in decreasing levels of depression in this sample of caregivers. Determining
      the effectiveness of this intervention in decreasing caregiver depression was
      difficult because caregivers with higher levels of depression were more likely to
      withdraw from the study. IMPLICATIONS FOR NURSING PRACTICE: Nurses must be
      vigilant in monitoring caregivers for signs of depression and must intervene to
      provide emotional support and make appropriate referrals for follow-up care to
      promote positive outcomes for patients and caregivers.

PMID- 11517849
TI  - Pain, mood disturbance, and quality of life in patients with multiple myeloma.
AB  - PURPOSE/OBJECTIVES: To determine the levels of pain intensity and pain
      interference in patients with multiple myeloma, the relationship between pain and
      mood disturbance, and factors that influence quality of life (QOL). DESIGN:
      Descriptive correlational mailed survey. SETTING: A private tertiary institution
      in the Midwest. SAMPLE: Convenience sample of 346 adult patients with multiple
      myeloma identified through an institutional database, 206 of whom responded to
      the surveys. METHODS: Mailed, self-administered questionnaires: Brief Pain
      Inventory Short Form, Profile of Mood States, QOL Scale (Cancer Patient Version),
      and a demographic tool. Treatment details were obtained from the database on
      subjects consenting to participate. MAIN RESEARCH VARIABLES: Pain intensity, pain
      interference, psychologic functioning, and QOL. FINDINGS: 29% (n = 60) of
      subjects reported moderate to severe pain intensity. Significant associations
      were found between pain intensity and mood disturbance scores. As pain
      interference increased, so did levels of mood disturbance. A joint predictive
      model explained 74.6% of the variability in total QOL scores. CONCLUSIONS: Cancer
      pain remains undertreated, and patients with myeloma are no exception. Pain and
      mood disturbance scores were significant predictors of QOL in this group of
      patients. Subjects with multiple myeloma reported higher levels of mood
      disturbance than patients with cancer from other studies. IMPLICATIONS FOR
      NURSING PRACTICE: The oncology nurse is in a key position to facilitate ongoing,
      adequate pain and psychosocial assessment of patients with myeloma. Further study
      is needed to determine if control of pain and mood disturbance factors has a
      positive effect on the various domains of QOL.

PMID- 11517850
TI  - Exploring the management of bone metastasis according to the Roy Adaptation
      Model.
AB  - PURPOSE/OBJECTIVES: To explore bone metastasis using Roy's Adaptation Model as a
      conceptual framework. DATA SOURCES: Published articles, conference abstracts,
      recent texts, and prescribing information. DATA SYNTHESIS: Bone metastasis has a
      significant impact on the patient's ability to maintain physical and psychosocial
      functions. Primary (self), secondary (family and occupation), and tertiary
      (community) roles, as identified by the Roy Adaptation Model, may be impaired as
      a result of bone metastasis. Patient education is a nursing intervention that
      frequently is used, as it allows an individual to interpret an aversive event and
      take action, thus promoting adaptation to illness. Medications for the underlying
      disease, bone metastasis, pain, and other symptoms warrant consideration. Active
      interventions, such as relaxation therapy, guided imagery, music, meditation, and
      therapeutic touch, also promote adaptation. CONCLUSIONS: Bone is a common and
      potentially debilitating site of metastasis. The presence of bone metastasis
      indicates progressive and, almost always, incurable disease. Patient adaptation
      can be enhanced through the proper use of palliative therapies and other nursing
      measures. IMPLICATIONS FOR NURSING PRACTICE: Oncology nurses can assist in the
      physical and psychosocial adaptation of patients with bone metastasis through
      assessment, patient education, and symptom management.

PMID- 11517851
TI  - Nurses' attitudes toward clinical trials at a comprehensive cancer center.
AB  - PURPOSE/OBJECTIVES: To identify nurses' attitudes and beliefs toward cancer
      clinical trials and their perceptions about factors influencing patients'
      participation in these trials. DESIGN: Descriptive. SETTING: National Cancer
      Institute-designated comprehensive cancer center. SAMPLE: 417 nurses employed at
      the cancer center were surveyed; 250 (60%) subjects responded. METHODS: 59-item
      questionnaire. MAIN RESEARCH VARIABLES: Nurses' attitudes toward clinical trials
      and perceptions of patient understanding of and influences on participation in
      clinical trials. FINDINGS: 96% of nurses reported that participation in clinical
      trials is important to improving standards of care; only 56% believed that
      patients should be encouraged to participate in trials if they had cancer. In
      multiple regression analyses, older age and being a research nurse were
      significant predictors of positive attitudes toward clinical trials. Work setting
      also was a significant predictor of nurses' perceptions of patients'
      understanding of treatment. Overall, nurses reported that an investigational
      therapy should have at least a 50% chance of success prior to being offered to
      patients. CONCLUSIONS: Nurses generally reported that clinical trials are
      important to improve standards of care; however, attitudes concerning patient
      participation in clinical trials and perceptions of patient understanding
      differed by work setting. Nurses have high expectations regarding the benefits of
      investigational therapy. IMPLICATIONS FOR NURSING PRACTICE: Nurses play a
      critical role in the care of participants in cancer clinical trials. Targeted
      interventions that involve nurses to enhance appropriate patient accrual, patient
      understanding, and patient decision making should result in improved patient care
      in centers conducting clinical trials.

PMID- 11517852
TI  - Clinical evaluation of human placental extract (placentrex) in radiation-induced
      oral mucositis.
AB  - To evaluate human placental extract in the treatment of radiation mucositis
      involving the oral/oropharyngeal region, a prospective randomized study was
      carried out in 120 patients with squamous cell carcinoma of the head and neck
      from August 1997 to March 1999. The study was conducted in patients receiving
      radical external radiation therapy, planned for = > 60 Gy/30 F/6 weeks, who
      developed grade 2 radiation mucositis (patchy mucositis) during radiation
      treatment. The patients were randomized in two groups of 60 patients each to
      receive either placentrex treatment (placentrex group) or conventional treatment
      (control group). Placentrex treatment was given as Inj Placentrex 2 ml by deep
      intramuscular injection 5 days a week for 15 injections. Conventional treatment
      given in the control group was disprin gargles and betamethasone oral drops. A
      subjective decrease in pain was observed in 48/60 (80%) of patients in the
      placentrex group compared with 22/60 (36.7%) in the control group. The
      progression to grade 3 radiation mucositis was 24/60 (40%) in the placentrex
      group compared with 52/60 (86.7%) in the control group. The subjective
      improvement in difficulty in swallowing was seen in 56/60 (93%) of patients in
      the placentrex group compared with 9/60 (15%) of patients in the control group.
      Only one patient in the placentrex group compared with three in the control group
      required interruption of radiation therapy because of severe radiation reactions.
      Human placental extract appears to be effective in the management of radiation
      induced oral/oropharyngeal mucositis and especially in controlling subjective
      symptoms.

PMID- 11517853
TI  - The suppressive mechanism of histamine release from rat peritoneal mast cells of
      iodine-enriched eggs.
AB  - We investigated the antiallergic activity of iodine-enriched egg by using rat
      peritoneal exudate cells. The effects were evaluated by the inhibition ratio of
      these compounds on histamine release from rat peritoneal exudate cells. Lipid and
      water-soluble fractions, which were separated from iodine-enriched egg yolk, were
      used for all experiments. Lipid fractionation of iodine-enriched eggs inhibited
      histamine release by compound-48/80 in a dose-dependent manner. Lipid
      fractionation of ordinary eggs had no effect. Neither the water-soluble fraction
      of iodine-enriched eggs nor ordinary eggs inhibited compound-48/80 induced
      histamine release. Neither lipid nor soluble fraction of iodine-enriched eggs
      inhibited histamine release in peritoneal exudate cells with Ca ionophore A23187
      stimulation. The same fractions of ordinary eggs were also unable to inhibit
      histamine release. The lipid fraction, furthermore, was isolated to neutral and
      polar lipid fractionation. Although both neutral and polar lipid fractionation
      inhibited histamine release, the effect was dose-dependent in only neutral lipid
      fractionation. Neither fractions of ordinary egg inhibited histamine release. In
      conclusion, the components inhibiting histamine release in rat peritoneal exudate
      cells exist in the neutral lipid fraction of iodine-enriched eggs.

PMID- 11517854
TI  - The synergistic effect of lactic acid bacteria and alkylglycerols on humoral
      immunity in mice.
AB  - Investigations on immune suppression and reconstitution of immune functions
      dependent on the presence of physiological microflora allow us to conclude that
      symbiotic microorganisms such as Lactobacillus sp. are essential for adequate
      activity of the defense system in humans. In addition to their beneficial
      influence on the intestinal microbial balance, these microorganisms exert a
      variety of immunomodulatory effects on the host immune system. On the other hand,
      immunostimulatory animal-derived substances rich in alkylglycerols have been
      shown to enhance lactic acid bacteria proliferation. Therefore, the aim of the
      present study was to evaluate the effects on murine humoral response of the
      combined administration of lyophilized combination of three lactic acid bacteria:
      L. acidophilus, L. bulgaricus and Bifidobacterium bifidum together with
      alkylglycerol-rich shark liver oil. The lactic acid bacteria mixture induced
      markedly stronger enhancement of the humoral response than alkylglycerols did. A
      significant synergistic stimulatory effect of lactic acid bacteria and
      alkylglycerols was observed in both treatment schedules: post- as well as in
      preimmunization with sheep red blood cells. However, their concomitant
      administration exerted stronger immunomodulatory effect than did the alternative
      route of treatment.

PMID- 11517855
TI  - Inhibitory effect of Avene spring water on vasoactive intestinal peptide-induced
      inflammation in surviving human skin.
AB  - The aim of this study was to evaluate the antiinflammatory effect of Avene spring
      water on skin fragments stimulated by a neuromediator, vasoactive intestinal
      peptide (VIP). Skin fragments (from plastic surgery) were maintained for 6 h. To
      induce inflammation, VIP was applied on contact with the dermis by culture
      medium. Cellulose patches containing Avene spring water were applied over the
      epidermis at the same time. Histological analysis was then performed on
      hematoxylin and eosin stained slides. Edema was evaluated with semiquantitative
      scores. Vasodilation was studied by calculating the percentage of dilated vessels
      according to scores and by measuring the surface of these dilated vessels by
      morphometrical image analysis. Tumor necrosis factor (TNF)-alpha dosage was made
      on culture supernatants. Edema was significantly increased after application of
      VIP compared with untreated skin. Treatment with cellulose patches containing
      Avene spring water showed decreased edema in comparison with cellulose patches
      containing distilled water. Vasodilation was significantly increased after
      application of VIP. After treatment with Avene spring water, the percentage and
      the surface of dilated vessels were significantly decreased. Moreover, treatment
      with cellulose patches containing Avene spring water showed a decrease in TNF
      alpha compared with skins treated with VIP.

PMID- 11517856
TI  - Cetirizine reduces the number of tryptase-positive mast cells in psoriatic
      patients: a double-blind controlled study.
AB  - Psoriatic plaque contains an increased number of mast cells that are thought to
      play an important role in the initiation and maintenance of the disease through
      the release of mediators such as histamine, proteoglycans, proteinases and
      cytokines. To verify the possible participation of these cells in the chronic
      inflammatory cutaneous response in psoriasis, we performed a double-blind
      controlled study to investigate the presence and activation of tryptase-positive
      mast cells in the lesional skin of 19 patients affected by active psoriasis
      vulgaris minima compared with five healthy, age-matched subjects. Psoriatic
      patients were randomized into two groups (A and B). The first group was treated
      with cetirizine (10 mg/three times a day for 15 days) and the second one was
      treated with placebo. Both groups underwent clinical staging [psoriasis area and
      severity index (PASI) score] and immunohistochemical evaluation [alkaline
      phosphatase antialkaline phosphatase (APAAP) procedure] before and after
      treatment. In group A, the PASI score ranged from 3.8 (SE +/- 1.00) to 1.8 (SE +/
      0.68) and in group B, from 5.0 (SE +/- 0.98) to 3.4 (SE +/- 0.47). The mean
      number of tryptase-positive mast cells for field, mainly distributed in the
      perivascular and periadnexal sites, ranged from 40.8 (SE +/- 7.15) to 21.6 (SE +/
      3.04) in group A and from 25.1 (SE +/- 3.78) to 26.3 (SE +/- 3.59) in group B
      (ANOVA test f = 6.95; gl = 1.16; p = 0.02). In our psoriatic patients, cetirizine
      significantly reduced the expression of tryptase-positive mast cells and produced
      a clinical improvement in erythema, suggesting a multilevel immunopharmacologic
      modulation of this antihistamine in psoriasis.

PMID- 11517857
TI  - Facility profile. 'Mission' offers healing aesthetics.

PMID- 11517858
TI  - Rise of the robots. New surgery technologies are proving to be hassle-free--for
      now.

PMID- 11517859
TI  - Partnering for safety. Facility managers take advantage of voluntary OSHA
      program.

PMID- 11517860
TI  - Cleaning up. Laundry operations can become valuable moneymakers.

PMID- 11517861
TI  - Antimutagenicity of extracts of Hericium erinaceus.
AB  - Hericium erinaceus is valuable in the diet and in medical treatment. It contains
      water-soluble polysaccharides that have been found to enhance immunity and which
      show anti-artificial pulmonary metastatic tumor effects. In this study, water and
      ethanol extracts of the mycelium and fruiting body of Hericium erinaceus were
      examined by the Ames test using Salmonella typhimurium TA98 to screen for
      antimutagenic effects against 5 mutagens: AFB1, B[a]P, Glu-P-1, NQNO, and Trp-P
      1. We found that both extracts have the strongest antimutagenic activity against
      Trp-P-1, followed by Glu-P-1, B[a]P-1, AFB1, and finally NQNO. In addition, the
      antimutagenicity of the extracts was produced in a concentration-dependent
      manner. At a concentration of 200 ppm, both extracts showed the highest
      inhibitory action. However, the linear correlation indicated that concentration
      activity relationship was not significant (p > 0.05). In addition, extracts
      showed less antimutagenicity after heat treatment (p < 0.05). This suggests that
      the antimutagenicity of the extracts is heat-labile. The ethanol extract from
      mycelium or fruiting body had better antimutagenic effects than did the water
      extract (p < 0.05). Also, the extract from the fruiting body had better
      antimutagenic effects than did that from the mycelium.

PMID- 11517862
TI  - Serial changes of cardiac troponin-I in acute myoischemia induced by exercise
      treadmill test.
AB  - Cardiac troponin-I (cTn-I) is a sensitive and specific marker for the diagnosis
      of acute myocardial infarction (AMI). However, elevation of serum cTn-I has been
      observed in some unstable angina patients who have a worse prognosis than those
      with normal serum cTn-I levels. It is unknown whether serum cTn-I can elevate in
      stable angina patients with acute ischemic burden. Therefore, the purpose of this
      study was to determine a serial change of cTn-I in patients with acute ischemia
      induced by a treadmill exercise test. Thirty-five patients suspected of having
      coronary artery disease and five healthy medical students were enrolled into this
      study. Every patient received a treadmill exercise test. Cardiac troponin-I was
      measured by fluorescent immunoassay before the treadmill test and at 5 minutes, 1
      hour, 3 hours, and 6 hours after the treadmill test. Patients with cTn-I levels
      of less than 0.5 ng/ml were considered normal, and those with cTn-I levels of
      greater than 2.0 ng/ml was considered to have AMI. The exercise test was positive
      in 19 of the 35 patients and negative in 16 of the 35 patients and 5 medical
      students. Among the 19 patients with positive treadmill exercise test, the cTn-I
      concentrations were abnormally increased in 7/19 (37%) patients (mean: 1.1 +/-
      0.4 ng/ml; range: 0.5 to 2.0 ng/ml). One of the 16 patients with negative
      treadmill test showed an increase of serum cTn-I. Normal cTn-I levels were found
      in the other 15 patients and the 5 medical students. In conclusion, serum cTn-I
      levels were found to increase to some extent in one third of stable angina
      patients who have an acute ischemic episode induced by treadmill exercise test.

PMID- 11517863
TI  - Ventilatory defect in coal workers with simple pneumoconiosis: early detection of
      functional abnormalities.
AB  - Airway obstruction is a prominent feature in coal workers' pneumoconiosis (CWP).
      However, many patients with CWP have even demonstrated a normal forced vital
      capacity (FVC) and forced expiratory volume in 1s (FEV1). The purpose of this
      study was to evaluate the ventilatory defect by spirometry and search for
      parameters, other than FVC and FEV1, suitable for early detection of pulmonary
      impairment in CWP. A sample of 227 coal miners was selected from the medical
      clinics of two teaching hospitals. Maximal expiratory flow volume measurement and
      determination of functional residual capacity (FRC) and residual volume (RV) were
      carried out with an automated plethysmograph. The prevalence of airway
      obstruction (FEV1/FVC < 70%) in this sample of miners was 52.9% (120/227). There
      was a progression of functional impairment with the transition from category 0 to
      categories 2 and 3, no matter what the miners smoking habits. All of the 107 non
      obstructed miners had a normal FVC and FEV1. However, the mean values for FEF25
      75% (mean forced expiratory flow during the middle half of FVC) and Vmax50
      (maximal expiratory flow rate at 50% FVC) were abnormally low, and RV was already
      elevated, in those non-obstructed subjects with category 1 simple pneumoconiosis.
      A borderline abnormally elevated FRC in the miners with radiological category 3
      of CWP was also noted. We conclude that the Vmax50, FEF25-75%, and RV appeared to
      be the discriminative indices for detecting early ventilatory defect in non
      obstructed patients with simple CWP. Further studies is still needed to clarify
      the cause of small airway dysfunction.

PMID- 11517864
TI  - A multidimensional assessment of insights in schizophrenic patients.
AB  - This study aims to construct a multidimensional instrument in assessing insight
      of schizophrenic patients and further to examine its relationships with other
      factors such as psychiatric symptoms, demographic characteristics, and course of
      illness. An instrument (the Schedule for assessment of Insight in Psychosis, SIP)
      with a 4-point rating scale was constructed to assess the insight of
      schizophrenic patients in five dimensions. One hundred schizophrenic patients
      were recruited for the study and all of them received a semi-structured interview
      using the SIP. Their demographic variables, length of illness and severity of
      psychotic symptoms were analyzed for insight. The reliability and validity of the
      SIP were satisfactory. Significant factors related to insight were psychotic
      symptoms, including both positive and negative symptoms. This study showed
      insight was affected by a multitude of factors, and it could be assessed
      quantitatively in various dimensions.

PMID- 11517865
TI  - Prevalence and correlates of substance use among clinical nurses in Kaohsiung
      city.
AB  - Though substance abuse and its deleterious health sequelae are a serious problem
      in Taiwan, licit and illicit substance use patterns among nurses are
      understudied. The purpose of this study was to investigate the prevalence of
      substance use and to identify its related factors among clinical nurses. A total
      of 907 registered nurses were recruited for this study via stratified-random
      sampling from hospitals in Kaohsiung city. Each participant was requested to
      reply to a structured questionnaire anonymously and a 98.1% response rate was
      achieved. Prevalence of substance use during the past year was estimated as
      follows: alcohol drinking (regular use-3.8%); coffee drinking (regular use
      44.7%); cigarette smoking (regular use-0.2%); regular use of analgesics 21.1%;
      regular use of benzodiazepines 1.8%; use of narcotics (ever use-0.7%).
      Significant factors related to substance use were analyzed by logistic
      regression. This revealed that for regular alcohol use, the significant factor
      was a positive attitude toward substance use; for BZD drug use, they were poor
      mental health, positive attitude toward substance use, being unmarried, and used
      analgesics; for regular analgesics use, they were work in non-critical care unit,
      self-perceived poor health status, and BZD drug use. Results generated from this
      study may act as reference for nursing administration to develop an effective
      health promotion program of physical and mental health for the clinical nurses.

PMID- 11517866
TI  - Torsion of benign serous cystadenoma of the fallopian tube: a challenge in
      differential diagnosis of abdominal pain in women during their childbearing years
      -a case report.
AB  - The differential diagnosis of abdominal pain in women during their childbearing
      years is still a challenge. Abdominal pain caused by isolated tubal torsion is
      extremely rare. In the report, we presented a case of isolated tubal torsion
      caused by benign serous cystadenoma. A 28-year-old married woman (G0) having
      lower abdominal pain and nausea was referred to our Emergency Room with suspicion
      of ovarian mass. Physical examination, transvaginal ultrasound and computed
      tomography showed a 4-cm right adnexal cystic mass. Other laboratory data were
      all within normal limits. She was managed by laparoscopic examination due to a
      lack of improvement in her clinical symptoms and inclusive diagnosis after 48
      hours' conservative treatment. Laparoscopy showed isolated torsion of right
      fallopian tube but the right ovary was normal without torsion. Initially,
      detorsion was performed but necrotic change of the fallopian tube persisted
      because of permanent darkened color tube without blood flow redistribution, so
      salpingectomy was performed 30 minutes later. Final pathology showed benign
      serous cystadenoma of fallopian tube. The present case is the first case of
      benign serous cystadenoma with resultant necrotic tubal torsion. We reported this
      case to emphasize the possible value of early performance of laparoscopy in
      aiding an accurate diagnosis.

PMID- 11517867
TI  - Bladder wall calcification after intravesical chemotherapy with mitomycin C--a
      case report.
AB  - Bladder wall calcification has relatively few etiologies. We present such a case
      and review the literature to discuss it and the method for management. This case
      suffered from bladder wall calcification about 3 years after intravesical
      chemotherapy of mitomycin C. It was found accidentally during the transurethral
      resection of recurrent bladder tumor. The pathology confirmed the recurrence of
      transitional cell carcinoma combined with marked calcification. A repeat
      cystoscopy was done 3 months later. Massive calcified deposits in bladder wall
      especially in lesion of previous transurethral resection were still noted.
      Randomized biopsy showed dystrophic calcification without evidence of malignancy.
      We suggest that biopsy and/or resection (if possible) is a reasonable approach to
      eliminate the possibility of invasive bladder cancer.

PMID- 11517868
TI  - A case of pulmonary endometriosis--a rare case report and a successful treatment
      experience.
AB  - Endometriosis is a common disease found in reproductive age women, but pulmonary
      endometriosis is rare. We present a 21-year-old female with catamenial chest
      pain, chest tightness, severe cough, and hemoptysis. Though we could not find any
      definite intrapulmonary endometriotic lesion by computed tomography and
      bronchoscope, she was diagnosed to have pulmonary endometriosis due to the
      typical clinical symptoms. After 6 months of GnRH agonist application, the
      symptoms were completely relieved. She has been followed up and has been symptoms
      free for at least 6 months after administration of GnRH agonist.

PMID- 11517869
TI  - [Prenatal and postnatal prevention of iodine deficiency in the first year of
      life].
AB  - A total of 260 females were studied in an iodine-deficient regions in different
      periods of gestation. Among them, 123 females were examined during pregnancy and
      within 3 months of lactation. Iodine deficiency during pregnancy was shown to
      form a high risk for diseases in both a child and a mother. There is an increased
      risk for severe complications of pregnancy and labor, for decreased weight and
      height, and for the worse status of a fetus and a baby of the first year of life.
      The use of iodine-containing drugs (100 micrograms iodine a day) is highly
      effective.

PMID- 11517870
TI  - [Functional suitability of iodinated casein in the prevention of iodine
      deficiency].
AB  - At least 1.5 billion in the world and over 100 million Russians live in iodine
      deficiency areas. The sequelae of this condition are well known. The paper
      discusses the properties of the iodinated lactoprotein caseoiodine designed by
      the MRRC researchers and its capacities and advantages for using in the
      prevention of iodine deficiency. The assimilation of iodine from caseoiodine
      corresponds to the body's status: it significantly accumulates more frequently in
      the thyroid in dietary iodine deficiency (Group 1) and to a lesser degree in
      adequate dietary iodine intake (Group 2) and, by hour 72, amounts to 36.3 and
      31.4% of the ingested amount, respectively (P < 0.05). The findings are in
      agreement with the data available in the literature on the involvement of hepatic
      enzymes in regulating the metabolism of iodine during its intake in the protein
      (casein)-bound form and in increasing its fecal excretion (up to 40% in Group 2)
      whereas 95% iodine excrete with urine when inorganic iodine is consumed.

PMID- 11517871
TI  - [Natural deficiency of trace elements and ways of its prevention].
AB  - Eighty female adolescents living in the area where goiter is endemic were
      examined. The rates of increases in height and weight under 10 years were found
      to lag behind and, on the contrary, to excel their standard values in
      adolescence. The accelerated increases in height and weight in girls aged 11 to
      15 years were attended by rises in morbidity rates. The number of children with
      normal sexual development in the area of goiter endemics was reduced to 28.8% and
      the prevalence of menstrual dysfunction increased up to 54.8%. Impaired menstrual
      function was most frequently recorded in girls with changed levels of follicle
      stimulating and interstitial cell-stimulating hormones.

PMID- 11517872
TI  - [Sanitary and technological solutions of the elimination of iodine deficiency by
      iodination of drinking water].
AB  - Comprehensive studies of the sanitary standards provided research evidence for
      the maximum allowable concentrations of iodine in the drinking water by taking
      into account its daily allowances dose and the formation of transformation by
      products due to iodine disinfection, drinking water preservation, and iodine
      deficiency prevention in the endemic areas. Techniques of water iodination have
      been devised and tested in the experimental and industrial setting, including
      those for packaging drinking water, as well as those by using portable water
      purifiers based on highly effective iodine-selective adsorptive compounds which
      make it possible to solve the task of administering iodine dosages into the water
      (with allowances born in mind), under domestic conditions as well.

PMID- 11517873
TI  - [Iodine deficiency in the Russian Federation].
AB  - Epidemiological surveys for iodine deficiency (ID) were made in 30 regions of
      Russia in 1992 to 1999. A total of 40,999 individuals aged 7 to 17 years were
      examined. The advent of new assessments of the thyroid and new indicators of
      iodine deficiency has changed approaches to epidemiological surveys. The WHO
      standards for estimating the prevalence and severity of ID have been introduced
      into Russian practice. In Central Russia, the lowest (median 30-58 micrograms/l)
      iodine concentrations were found in rural dwellers; in more urbanized areas
      (cities, towns) the median was 50-78 micrograms/l. ID was more pronounced in the
      regions of East Russia where it was predominantly moderate (median 30-52
      micrograms/l). In some areas, ID was severe (median 16-20 micrograms/l). As the
      severity of ID increases, the incidence of such conditions, as goiter,
      hypothyroidism, endemic cretinism is on the rise. Mild to moderate goiter endemia
      prevailed in Central Russia. The manifestations of goiter endemia were more
      pronounced in rural children (18-30%) than in urban ones (8-14%). East Russia was
      marked by moderate to severe goiter endemia (8-14%): the incidence of goiter
      ranged from 17 to 40%. There were only sporadic cases of goiter in some areas of
      the Sakhalin Region. In the Moscow and Voronezh Regions and the Republic of
      Kalmykia there were areas showing a high goiter incidence which did not
      correspond to the level of ID. An epidemiological analysis has indicated that
      dietary and water iodine intake is decreased in most regions of Russia. The
      actual dietary iodine intake was 40-80 micrograms/day, i.e. 2-3 times of the
      recommended allowance (150 micrograms). The Endocrinology Research Center has
      tested different models of preventive and therapeutical measures for eliminating
      iodine deficiency-caused diseases by using iodinated foodstuffs (salt, bread,
      butter) ad iodine medicaments.

PMID- 11517874
TI  - [Selenium as an essential and deficient factor in the nutrition of Russian
      population].
AB  - The paper presents summarized data on the metabolism of selenium and approaches
      to justifying physiological requirements for this micronutrient. The studies
      dealing with the levels of selenium in different foodstuffs have indicated that
      they are lower in the foods made in Russia than in those made in foreign
      countries, which leads to its insufficient dietary intake in Russia's population,
      in poor ecological regions in particular. Experimental studies have revealed that
      organic selenium compounds exert a beneficial effect on the metabolism of
      priority food pollutants, such as mycotoxins and N-nitrosoamines.

PMID- 11517875
TI  - [Caries and fluorine: role of water factor, problems and solutions].
AB  - The epidemiological studies of the severity and spread of caries of deciduous and
      permanent teeth in Moscow schoolchildren (n = > 20,000) aged 7-17 years in
      relation to the content of fluoride in the drinking water, to the use of fluorine
      containing tablets and varnishes have provided evidence for the high efficiency
      of drinking water fluorination for the primary prevention of caries as compared
      with other preventive alternatives. Based on sanitary studies, two main lines are
      now under way in solving the problem connected with low dietary fluoride intake:
      the introduction of routine water-purifying fluorine generators (based on a new
      technology of fluorination of limited water volumes for drinking and cooking) and
      the setting-up of plants manufacturing bottled drinking waters containing the
      optimum or higher fluorine levels for provision of different population groups,
      primarily children and pregnant women in particular.

PMID- 11517876
TI  - [Identification of specific features of the development of iodine deficiency in
      children exposed to low-intensity ecological factors (in case of the Perm
      Region)].
AB  - Iodine deficiency is an important sociomedical problem in most regions of Russia,
      including the Perm Region. In this connection, to study the low combined
      influence of a complex of natural (iodine deficiency) and man-made (aerogenic
      polluting components) factors on human health is urgent. Clinical and laboratory
      screenings of children were performed in 20 areas of the Perm Region, which have
      various anthropogenic loads. Varying iodine provision was established for the
      first time by urinary iodine values (median concentrations). There were
      characteristic manifestations of thyroid dysfunction in children and thyroid size
      alterations as hyperplasia. The blood levels of trace elements were measured in
      the children. There was a mutual interaction of excessive and deficient trace
      elements with the concentration of thyroid hormones and the level of ioduria. The
      study areas were classified by the indices reflecting iodine deficiency. The
      priority indices required for consideration in drawing up regional programmes for
      preventing and correcting iodine deficiency in the population were defined. Thus,
      the study have demonstrated that the factors of aerogenic load promote the
      aggravation of iodine deficiency in the children of the Perm Region, which should
      be born in mind in their prevention and correction.

PMID- 11517877
TI  - [Free radical oxidation as a link of early and prolonged adaptation to
      environmental factors].
AB  - Analyzing his own findings and the data available in the literature, the author
      has found that free radicals are a connecting link in the development of early
      and prolonged adaptation. With rapid adaptation, they make a weighty contribution
      to the body's bactericidal protection and antimicrobial constitutional immunity.
      This role is mainly played by the oxygen-dependent phagocytic bactericidal system
      that generates active oxygen forms and by the inducible arginine-dependent
      connective tissue cell system that synthesizes nitrogen oxide. While performing,
      the above enzymatic systems spend their cell energy resources on two concurrent
      processes: the formation of free radical products and the work of ionic pumps
      that restore an intracellular ionic and osmotic balance. This causes the
      accelerated expenditure of the body's energy "currency" ATP and the development
      of energy deficiency in the cells and tissues. Energy shortage serves as a signal
      for triggering the cellular genetic apparatus to primarily induce the increased
      development of the cell energy system, namely that of mitochondria, and the
      activation of the key systems responsible for steady-state long-term individual
      adaptation of the immune system, antioxidative protection, etc. It has been now
      ascertained that there is a common pathogenetic link (excessive production of
      free radicals) in the mechanism responsible for the influence of not only
      infections on the body, but other environmental factors (fibrogenic dust,
      ionizing or ultraviolet radiation, cooling, toxic agents oxidized on cytochrome P
      450, hypoxia, hyperoxia, etc.) and vital functions (physical overstrain,
      emotional stress, informational overload, etc.). The above factors all cause the
      same metabolic change in different ways: the production of higher quantities of
      active oxygen forms, nitrogen oxide, and other radical products. So the
      generation of free radicals is an universal connecting link of early and
      prolonged adaptation. The fact that there is a common link (the excessive
      production of radicals) in the mechanism of influence of environmental factors
      and vital activities makes the most important biological reserve (cross
      adaptation that lies in higher resistance to the whole complex of active
      influences at adaptation to one of them) serve as a preventive means. The most
      rapid increase in the production of free radicals and the development of energy
      rich products are achieved by hypoxia. So the adaptive and preventive effect of
      dosage hypoxia are the most pronounced.

PMID- 11517878
TI  - [Need for studies aimed at the prevention of oncologic diseases].

PMID- 11517879
TI  - [The influence of epileptic predisposition on clinical features of schizophrenia
      in patients after delirium tremens].
AB  - 153 patients with schizophrenia in combination with alcoholic delirium were
      examined. Latent epilepsy has been found in 36 patients (23.5%). The basis of the
      epileptic seizures during alcoholic delirium was hereditary epileptic
      predisposition. Frequency of the progredient course was high while that of the
      favourable--recurrent course of schizophrenia was low in these cases.

PMID- 11517880
TI  - [Diagnosis and therapy of resistant temporal epilepsy].
AB  - A complex research of epileptogenic focus (electroencephalography, invasive
      electroencephalography, MRI, PET) has allowed to localize a primary epileptogenic
      zone in medial temporal epilepsy in amygdale in 52% of the patients, in the
      anterior hippocampus--in 30% cases, a simultaneous and equivalent involvement of
      both amygdale and anterior hippocampus was diagnosed in 18% of the patients
      examined. Stereotaxic selective amygdalehippocampotomy was found to be effective
      in patients with resistant medial and lateral temporal epilepsy. The attacks
      stopped in 36% of the cases. In other patients frequency and duration of
      epileptic paroxysms considerably reduced, the structure of the paroxysms changed.

PMID- 11517881
TI  - [Depakene (sodium valproate) in the treatment of epilepsy in children and
      adolescents: efficiency and safety].
AB  - 375 patients 7 months-19 years of age with different forms of epilepsy were
      treated with depakine. High efficiency of the drug was found in all forms of
      children's epilepsy. A complete remission was observed in 60% of the patients, a
      good effect--in 19%, a satisfactory effect--in 15%, 6%--were non-responders. The
      highest efficiency of depakine was achieved in idiopathic forms of epilepsy
      (complete remission--in 74% of the cases) and, therefore, depakine can be used as
      a monotherapy. Meanwhile, the efficiency of depakine was lower in cryptogenic
      generalized and symptomatic partial epilepsy. In such cases depakine should be
      used as a basic preparation in polytherapy. Side effects were observed in 35% of
      the cases, but stopping of therapy was necessary only in 25% of such cases. Rare
      idiosyncrasy and no negative influence on the cognitive functions were important
      properties of depakine.

PMID- 11517882
TI  - [Location of equivalent dipole sources of paroxysmal activity in patients with
      posttraumatic epilepsy].

PMID- 11517883
TI  - [Dynamics of the personality profile and cognitive functions in finlepsin
      treatment of partial epilepsy].
AB  - The aim of modern antiepileptic therapy is not only to decrease frequency of the
      seizures and to prevent their rise, but to decrease negative consequences of the
      treatment too. It is, first of all, to decrease the influence of the
      antiepileptic preparations on the cognitive functions and, therefore, on quality
      of the patients' life. During therapy of 40 patients (8-57 year-olds) with
      partial epilepsy the severity of the seizures as well as emotional and cognitive
      functions of the patients were evaluated. A significant decrease of the severity
      of the seizures was observed during therapy with finlepsin-retard (p < 0.002).
      These changes correlated both with a decrease of anxiety according to MMPI
      questionnaire (p < 0.0001) and with an increase of the volume of the short-term
      imaginary memory. Finlepsin-retard is effective therapy for epilepsy.

PMID- 11517884
TI  - [Neurophysiological features in epileptic patients with affective disorders].
AB  - The paper presents an analysis of autonomic regulation and spectral EEG structure
      in 70 epileptic patients with affective disorders in period between the fits. It
      was found that activity of the sympathetic link was elevated, activity of the
      parasympathetic link was decreased in such patients especially in cases with
      partial visceral-autonomic fits. EEG mapping revealed elevation of the spectral
      power of density (SPD) of alpha-diapason with a simultaneous decrease of 8-9 Hz
      frequency as well as different location of alpha-rhythm's focus in the patients
      as compared with healthy individuals. The most frequent prevalence of delta
      activity was found in the temporal lobes. In patients with partial visceral
      autonomic, psychomotor and psychosensory fits the foci of epileptic activity have
      been registered in the right hemisphere 3-4 times more frequently than in the
      left one. After the course of therapy normalization of the indices of autonomic
      regulation was not observed, individual EEG peculiarities remained, but there was
      an increase of alpha-rhythm's SPD and a decrease of SPD of delta-range.

PMID- 11517886
TI  - [Culturally determined Dhat syndrome].

PMID- 11517885
TI  - [Features of neurotransmitter pool in cerebrospinal fluid of patients with
      epilepsy].
AB  - The paper deals with the state of neurotransmitter pool in cerebrospinal fluid of
      epileptic patients. There were significant peculiarities of the dynamics of both
      excitatory (glutamate, aspartate) and inhibitory (GABA, glycine, taurine)
      neurotransmitters in respect of the severity of the pathologic process, frequency
      and type of convulsive seizures. The correlation found between a degree of the
      disease severity and a level of glutamate in cerebrospinal fluid after the
      seizures and between them could be a criterion for the prognosis of epilepsy.

PMID- 11517887
TI  - [Pharmacotherapy of epilepsy in elderly patients].

PMID- 11517888
TI  - [Callosotomy in therapy of resistant forms of epilepsy].

PMID- 11517889
TI  - [Sudden death syndrome in epilepsy].

PMID- 11517890
TI  - [Posttraumatic epilepsy: diagnosis and clinical variety].
AB  - 125 patients with posttraumatic epilepsy (PTE) were examined using methods of
      neurovisualization (CT and MRI) and electroencephalography (EEG), including brain
      mapped EEG. The research resulted in the conclusion about heterogeneity of the
      disease. Differential diagnostic criteria were elaborated for three clinical
      variations of symptomatic epilepsy of the traumatic genesis. Besides, the second
      variation was a real PTE, with the most clear clinical signs. The knowledge about
      the ambiguous clinical pattern of the disease may improve therapy and prognosis,
      evaluate both physical and occupational abilities of the patients more
      objectively.

PMID- 11517891
TI  - [Neonatal resuscitation with 100% oxygen].

PMID- 11517892
TI  - [Cyanoacrylates: another way to repair wounds].

PMID- 11517893
TI  - [Hematomas with morphology suggesting intention].

PMID- 11517894
TI  - [Atopic dermatitis and topical wheat: always friends?].

PMID- 11517895
TI  - [Accidental ingestion of toxic substance in a 2-year-old child].

PMID- 11517896
TI  - [Chondrosarcoma of the first toe phalanx. A case report].

PMID- 11517897
TI  - [Clinical aspect of platelet adhesion disorders].

PMID- 11517898
TI  - Clinical pictures of malnutrition in ill elderly subjects.
AB  - Malnutrition in ill elderly subjects is common in hospitals, nursing homes, and
      home care. Depending on the type and composition of the groups of patients under
      consideration, the prevalence of malnutrition is cited at up to 60%. With
      advancing age, the amounts of food consumed daily diminish and become
      significantly smaller than the amounts consumed by the younger population. The
      elderly mostly eat food of low nutrient density. Especially at times of high
      energy requirements such as acute or chronic illness, this results in an energy
      deficit and general malnutrition. Precise diagnosis of malnutrition can be
      facilitated by determination of a number of biochemical parameters. Knowledge of
      these permits individualized nutrition therapy. The most important deficits
      affecting ill elderly subjects are those relating to proteins, iron, zinc,
      selenium, and vitamins B12, B1, B6 and D. Malnutrition prolongs hospital stays,
      imposes enormous costs on health services, and causes considerable mortality. The
      present, very rapid increase in the size of the elderly population will
      exacerbate the problem of malnutrition. Therefore more attention should be paid
      to malnutrition by treating it as a disease in its own right and including it in
      the training of doctors and nurses.

PMID- 11517899
TI  - [A prospective study on histological and serological changes after interferon
      alpha-2b treatment in patients with chronic hepatitis B infection].
AB  - OBJECTIVE: To investigate the histological changes in liver biopsies and HBV DNA
      changes in sera induced by 18 weeks of interferon alpha-2b therapy in patients
      with chronic hepatitis B infection. METHODS: Twenty-two patients were enrolled
      into this prospective study. All patients had a liver biopsy within 1 week before
      starting interferon therapy. Interferon alpha-2b was given at a dose of 3MU
      thrice a week for 18 weeks. A second liver biopsy was taken for comparison at the
      end of week 18. Blinded biopsies were scored according to Knodell's histology
      activity index (HAI), and examined for HBsAg, HBeAg, HBcAg and alpha - SMA by
      immunohistochemistry. The serum samples corresponding with liver biopsies were
      collected and HBV DNA, e-antigen were measured. RESULTS: Histological assessment
      revealed a significant improvement in intralobular inflammation and periportal
      necrosis after treatment(P<0.01). Fifty-five percent (12/22) patients had a
      reduction of hepatic necroinflammatory HAI score at the end of 18 weeks of
      interferon alpha-2b therapy compared to pretreatment values, but periportal
      inflammation and fibrosis failed to show improvement. HBeAg disappeared from
      liver tissues in 7 from 13 cases(53.8%)and a significant reduction of activated
      liver stellate cells was demonstrated in biopsies performed after suspending the
      interferon treatment(P=0.0004). Serum HBV DNA levels decreased significantly
      after treatment (P<0.01). The clearance rate of HBeAg was 42.9% after treatment.
      There was no significant difference between HBeAg positive and negative patients
      either in liver histological improvements or declining level of serum HBV DNA.
      CONCLUSIONS: Interferon alpha-2b may decrease the level of serum HBV DNA in the
      patients with chronic hepatitis B infection, and improve their necroinflammation
      in liver tissues.

PMID- 11517900
TI  - [Effect of vascular endothelial diphosphate glucuronosyltransferase mRNA
      regulated by alcohol].
AB  - OBJECTIVE: To investigate the effect of vascular endothelial growth factor(VEGF)
      gene transfection on tissue vascularization in transplanted site and the
      proliferation of transplanted hepatocytes. METHODS: Samples were gained at ten
      days after the pcDNA3 VEGF121 gene transfected hepatocyte was transplanted into
      the spleen of SD rats. The changes of microvascular density(MVD) counts in the
      transplanted site and proliferating cell nuclear antigen(PCNA) index of the
      transplanted hepatocytes were examined. RESULTS: In vitro protein expression of
      VEGF gene was enough to induce proliferation of human umbilical venous
      endothelial cells. In vivo VEGF gene transfected hepatocytes could form mass
      colonization of transplanted hepatocytes and reconstituted liver tissue.
      Difference of MVD counts in the transplanted site on all groups were not
      significant. P>0.05; PCNA index of pcDN-A3 VEGF121 gene transfection group
      increased significantly compared with pcDNA3 control group and no transfection
      group, P<0.01. PCNA index were 13.13 +/- 2.75, 4.75 +/- 1.58, and 4.63 +/- 1.41,
      suggesting that in vivo many factors affect the tissue vascularization, and
      expression of VEGF gene can promote not only proliferation of transplanted
      hepatocyte but formation of reconstituted liver tissue. CONCLUSIONS: VEGF ex vivo
      gene transfection is an effective way to induce reconstitution of transplanted
      liver tissue.

PMID- 11517901
TI  - [Quid? Localized right diaphragmatic eventration associated with dextrocardia].

PMID- 11517902
TI  - [Quid? Venous sacciform aneurysm of the extrahepatic portal trunk].

PMID- 11517903
TI  - [Quality management in imaging].

PMID- 11517904
TI  - [MRI of soft tissue tumors of the hand and wrist].

PMID- 11517905
TI  - [Clinical evaluation and current state of MRI low-field magnetics (<0,5 TESLA)
      equipment].

PMID- 11517906
TI  - Inhibin B in the assessment of seminiferous tubular function.
AB  - Inhibin B is a testicular hormone that regulates follicle-stimulating hormone
      secretion in a negative feedback loop. In males, the serum level of inhibin B is
      detectable throughout life, with a prominent change in the first year of life and
      during puberty, reflecting the testicular response to the activity of the
      hypothalamic-pituitary-gonadal hormone axis. During childhood, the basal serum
      inhibin B level is a direct marker of the presence and function of testicular
      tissue that has proved useful in the diagnosis of patients with cryptorchidism or
      ambiguous genitalia. In adult men, the inhibin B level is closely related to
      spermatogenesis. Measurements of serum inhibin B may provide valuable clues for
      the differential diagnosis of male infertility. A further exploration of the
      relationship between inhibin B, Sertoli cell function and spermatogenesis will
      improve the usefulness of inhibin B as a tool in the investigation of male
      reproductive health.

PMID- 11517907
TI  - Role of the cardiac lymph system in myocardial fluid balance.

PMID- 11517908
TI  - Detachment of the tricuspid valve to close ventricular septal defects.

PMID- 11517909
TI  - Dilation of knitted grafts in thoracic aorta.

PMID- 11517910
TI  - A biological model for biomechanical testing of median sternotomy closure.

PMID- 11517911
TI  - Structure of human muscle creatine kinase.
AB  - The crystal structure of human muscle creatine kinase has been determined by the
      molecular-replacement method and refined at 3.5A resolution. The structures of
      both the monomer and the dimer closely resemble those of the other known
      structures in the creatine kinase family. Two types of dimers, one with a non
      crystallographic twofold symmetry axis and the other with a crystallographic
      twofold symmetry axis, were found to exist simultaneously in the crystal. These
      dimers form an infinite "double-helix"-like structure along an unusual long
      crystallographic 3(1) axis.

PMID- 11517912
TI  - 10th World Congress of Ultrasound in Obstetrics & Gynecology, 4-7 October 2000,
      Zagreb, Croatia: presentations of the 2000 Ian Donald Medals. Presentation of the
      Ian Donald Gold Medal to Karek Marsal.

PMID- 11517914
TI  - [What to do in neuroleptic-induced sialorrhea].

PMID- 11517915
TI  - [Fear and molecular fundamental research].

PMID- 11517916
TI  - [A peripheral marker for schizophrenia: increased levels of D3-receptor-mRNA in
      blood lymphocytes].

PMID- 11517917
TI  - [Schizophrenia: one disease only with a broad scope of variations or a uniform
      syndrome of manifold different diseases--monism or pluralism].

PMID- 11517920
TI  - Quick disposal of dead cardiomyocytes: an ultimate proof of apoptosis.

PMID- 11517919
TI  - Smoothened mutants reveal redundant roles for Shh and Ihh signaling including
      regulation of L/R symmetry by the mouse node.
AB  - Genetic analyses in Drosophila have demonstrated that the multipass membrane
      protein Smoothened (Smo) is essential for all Hedgehog signaling. We show that
      Smo acts epistatic to Ptc1 to mediate Shh and Ihh signaling in the early mouse
      embryo. Smo and Shh/Ihh compound mutants have identical phenotypes: embryos fail
      to turn, arresting at somite stages with a small, linear heart tube, an open gut
      and cyclopia. The absence of visible left/right (L/R) asymmetry led us to examine
      the pathways controlling L/R situs. We present evidence consistent with a model
      in which Hedgehog signaling within the node is required for activation of Gdf1,
      and induction of left-side determinants. Further, we demonstrate an absolute
      requirement for Hedgehog signaling in sclerotomal development and a role in
      cardiac morphogenesis.

PMID- 11517921
TI  - Active "donor management" strategies may increase organ availability in lung
      transplantation.

PMID- 11517922
TI  - Re: Adaptive double data entry.

PMID- 11517923
TI  - Cysteine proteinases and their inhibitors--a traditional topic of the Portoroz
      conferences.

PMID- 11517924
TI  - Cysteine proteinases mediate extracellular prohormone processing in the thyroid.
AB  - Thyroglobulin, the precursor of thyroid hormones, is extracellularly stored in a
      highly condensed and covalently cross-linked form. Solublization of thyroglobulin
      is facilitated by cysteine proteinases like cathepsins B and K which are
      proteolytically active at the surface of thyroid epithelial cells. The cysteine
      proteinases mediate the processing of thyroglobulin by limited extracellular
      proteolysis at the apical plasma membrane, thereby rapidly liberating thyroxine.
      The trafficking of cysteine proteinases in thyroid epithelial cells includes
      their targeting to lysosomes where they become maturated before being transported
      to the apical plasma membrane and, thus, into the extracellular follicle lumen.
      We propose that thyroid stimulating hormone regulates extracellular proteolysis
      of thyroglobulin in that it enhances the rate of exocytosis of lysosomal proteins
      at the apical plasma membrane. Later, thyroid stimulating hormone upregulates
      thyroglobulin synthesis and its secretion into the follicle lumen for subsequent
      compaction by covalent cross-linking. Hence, cycles of thyroglobulin proteolysis
      and thyroglobulin deposition might result in the regulation of the size of the
      luminal content of thyroid follicles. We conclude that the biological
      significance of extracellularly acting cysteine proteinases of the thyroid is the
      rapid utilization of thyroglobulin for the maintenance of constant thyroid
      hormone levels in vertebrate organisms.

PMID- 11517925
TI  - Evolutionary lines of cysteine peptidases.
AB  - The proteolytic enzymes that depend upon a cysteine residue for activity have
      come from at least seven different evolutionary origins, each of which has
      produced a group of cysteine peptidases with distinctive structures and
      properties. We show here that the characteristic molecular topologies of the
      peptidases in each evolutionary line can be seen not only in their three
      dimensional structures, but commonly also in the two-dimensional structures. Clan
      CA contains the families of papain (C1), calpain (C2), streptopain (C10) and the
      ubiquitin-specific peptidases (C12, C19), as well as many families of viral
      cysteine endopeptidases. Clan CD contains the families of clostripain (C11),
      gingipain R (C25), legumain (C13), caspase-1 (C14) and separin (C50). These
      enzymes have specificities dominated by the interactions of the S1 subsite. Clan
      CE contains the families of adenain (C5) from adenoviruses, the eukaryotic Ulp1
      protease (C48) and the bacterial YopJ proteases (C55). Clan CF contains only
      pyroglutamyl peptidase I (C15). The picornains (C3) in clan PA have probably
      evolved from serine peptidases, which still form the majority of enzymes in the
      clan. The cysteine peptidase activities in clans PB and CH are autolytic only. In
      conclusion, we suggest that although almost all the cysteine peptidases depend
      for activity on catalytic dyads of cysteine and histidine, it is worth noting
      some important differences that they have inherited from their distant ancestral
      peptidases.

PMID- 11517926
TI  - Towards specific functions of lysosomal cysteine peptidases: phenotypes of mice
      deficient for cathepsin B or cathepsin L.
AB  - The lysosomal cysteine peptidases cathepsin B and cathepsin L are abundant and
      ubiquitously expressed members of the papain family, and both enzymes contribute
      to the terminal degradation of proteins in the lysosome. However, there is
      accumulating evidence for specific functions of lysosomal proteases in health and
      disease. The generation of 'knock out' mouse strains that are deficient in
      lysosomal proteases provides a valuable tool for evaluation of existing
      hypotheses and gaining new insights into the in vivo functions of these
      proteases. In this minireview, we summarise and discuss the findings obtained by
      analysis of mice that are devoid of cathepsin B or cathepsin L. In brief,
      cathepsin L appears to be critically involved in epidermal homeostasis,
      regulation of the hair cycle, and MHC class II-mediated antigen presentation in
      cortical epithelial cells of the thymus. Cathepsin B plays a major role in
      pathological trypsinogen activation in the early course of experimental
      pancreatitis and contributes significantly to TNF-alpha induced hepatocyte
      apoptosis.

PMID- 11517927
TI  - Calpain function in the modulation of signal transduction molecules.
AB  - Calpains are cytosolic cysteine proteases that are activated by a rise in
      intracellular Ca2+, and are believed to function in stimulating Ca2+ signaling on
      cell activation, leading the cell to differentiation, proliferation and death. In
      this review, we focus on the implication of calpains in signal transduction in
      molecules such as growth factors, T cell receptor, and integrin. Calpains are
      downstream molecules of hormone receptors, membrane-type tyrosine kinases and
      adhesion molecules, and proteolyze many signaling-related substrates. The
      substrates, protein kinase C (PKC), alpha subunit of G-proteins, and protein
      tyrosine phosphatases, are cleaved at interdomain site(s) and their activities
      are sustained or upregulated, while the fragments of focal adhesion kinase and
      the tyrosine kinase src family lose their activity. In the integrin cascade,
      calpains are upstream molecules of the Rho GTPase family, Rac1 or RhoA, and allow
      the lamellipodia formation. The significant activation of calpain suggests that
      calpain activity is regulated not only by an increase in intracellular Ca2+, but
      also by signaling that include the PKC-, tyrosine kinase- or the adhesion
      molecule-derived cascade. We have summarized these interesting phenomena, and
      speculate on the function and location of calpain in the signaling cascades.

PMID- 11517928
TI  - Structural basis for possible calcium-induced activation mechanisms of calpains.
AB  - The calpains form a growing family of structurally related intracellular
      multidomainal cysteine proteinases, which exhibit a catalytic domain distantly
      related to papain. In contrast to papain, however, their activity in most cases
      depends on calcium. The calpains are believed to play important roles in
      cytoskeletal remodeling processes, cell differentiation, apoptosis and signal
      transduction, but have also been implicated in muscular dystrophy, ischemia,
      traumatic brain injury, neurodegenerative diseases, rheumatoid arthritis and
      cataract formation. The best characterized calpains are the ubiquitously
      expressed mu- and m-calpains, consisting of a common 30 kDa small S-subunit
      (domains V and VI) and slightly differing 80 kDa large L-subunits (domains I to
      IV). We have recently determined the 2.3 A structure of recombinant full-length
      human m-calpain in the absence of calcium, which reveals that the catalytic
      domain and the two calmodulin-like domains, previously believed to represent the
      unique calcium switch, are not positioned adjacent to each other, but are
      separated by the beta-sandwich domain III, which distantly resembles C2 domains.
      Although the catalytic domain of apocalpain is strongly disrupted compared to
      papain (which explains its inactivity in the absence of calcium), the crystal
      structure reveals several sites where calcium could bind, thereby causing a
      subdomain fusion to form a papain-like catalytic center. All current evidence
      points to the cooperative interaction of several calcium binding sites. Sites
      identified include the three EF-hand binding sites in each calmodulin-like
      domain, the negatively charged segments arranged around the active-site cleft
      (provided by both catalytic subdomains), as well as an exposed acidic loop of
      domain III, whose charge compensation could allow the adjacent barrel-like
      subdomain IIb to move toward the helical subdomain IIa. The Gly-rich S-chain N
      terminus and the calcium-loaded acidic loop could target the conventional
      calpains to cellular/nuclear membranes, thereby explaining their strongly reduced
      calcium requirement in vivo and in vitro in the presence of acidic phospholipids.

PMID- 11517929
TI  - Autolysis of mu- and m-calpain from bovine skeletal muscle.
AB  - The rate of autolysis of mu- and m-calpain from bovine skeletal muscle was
      measured by using densitometry of SDS polyacrylamide gels and determining the
      rate of disappearance of the 28 and 80 kDa subunits of the native, unautolyzed
      calpain molecules. Rate of autolysis of both the 28 and 80 kDa subunits of mu
      calpain decreased when mu-calpain concentration decreased and when beta-casein, a
      good substrate for the calpains, was present. Hence, autolysis of both mu-calpain
      subunits is an intermolecular process at pH 7.5, 0 or 25.0 degrees C, and low
      ionic strength. The 78 kDa subunit formed in the first step of autolysis of m
      calpain was not resolved from the 80 kDa subunit of the native, unautolyzed m
      calpain by our densitometer, so autolysis of m-calpain was measured by
      determining rate of disappearance of the 28 kDa subunit and the 78/80 kDa
      complex. At Ca2+ concentrations of 1000 microM or higher, neither the m-calpain
      concentration nor the presence of beta-casein affected the rate of autolysis of m
      calpain. Hence, m-calpain autolysis is intramolecular at Ca2+ concentrations of
      1000 microM or higher and pH 7.5. At Ca2+ concentrations of 350 microM or less,
      the rate of m-calpain autolysis decreased with decreasing m-calpain concentration
      and in the presence of beta-casein. Thus, m-calpain autolysis is an
      intermolecular process at Ca2+ concentrations of 350 microM or less. If calpain
      autolysis is an intermolecular process, autolysis of a membrane-bound calpain
      would require selective participation of a second, cytosolic calpain, making it
      an inefficient process. By incubating the calpains at Ca2+ concentrations below
      those required for half-maximal activity, it is possible to show that unautolyzed
      calpains degrade a beta-casein substrate, proving that unautolyzed calpains are
      active proteases.

PMID- 11517930
TI  - Activation of progelatinase A by mammalian legumain, a recently discovered
      cysteine proteinase.
AB  - The activation of progelatinase A to gelatinase A requires cleavage of an
      asparaginyl bond to form the N-terminus of the mature enzyme. We have asked
      whether the activation can be mediated by legumain, the recently discovered
      lysosomal cysteine proteinase that is specific for hydrolysis of asparaginyl
      bonds. Addition of purified legumain to the concentrated conditioned medium from
      HT1080 cell culture that contained both progelatinases A and B caused the
      conversion of the 72 kDa progelatinase A to the 62 kDa form. The progelatinase B
      in the medium was unaffected. Incubation of recombinant progelatinase A with
      legumain resulted in an almost instantaneous activation as judged by the
      fluorometric assay with a specific gelatinase A substrate, Mca-Pro-Leu-Gly-Leu
      Dpa-Ala-Arg-NH2. Legumain also activated progelatinase A when it was in complex
      with TIMP-2. Zymographic analysis and N-terminal sequencing revealed that
      legumain cleaved the 72 kDa progelatinase A at the bonds between Asn109-Tyr110 or
      Asn111-Phe112 to produce the 62 kDa mature enzyme, and that further cleavage at
      Asn430 also occurred to generate a 36 kDa active form. More 62 kDa gelatinase A
      was detected in cultures of C13 cells that over-expressed legumain than in those
      of the control HEK293 cells. We conclude that legumain is clearly capable of
      processing progelatinase A to the active enzyme in vitro and in cultured cells.

PMID- 11517931
TI  - Imaging proteolysis by living human glioma cells.
AB  - Degradation of basement membrane is an essential step for tumor invasion. In
      order to study degradation in real time as well as localize the site of
      proteolysis, we have established an assay with living human cancer cells in which
      we image cleavage of quenched-fluorescent basement membrane type IV collagen (DQ
      collagen IV). Accumulation of fluorescent products is imaged with a confocal
      microscope and localized by optically sectioning both the cells and the matrix on
      which they are growing. For the studies described here, we seeded U87 human
      glioma cells as either monolayers or spheroids on a 3-dimensional gelatin matrix
      in which DQ-collagen IV had been embedded. As early as 24 hours after plating as
      monolayers, U87 cells were present throughout the 3-dimensional matrix. Cells at
      all levels had accumulated fluorescent degradation products of DQ-collagen IV
      intracellularly within vesicles. Similar observations were made for U87 spheroids
      and the individual cells migrating from the spheroids into the gelatin matrix.
      Both the migrating cells and those within the spheroid contained fluorescent
      degradation products of DQ-collagen IV intracellularly within vesicles. Thus,
      glioma cells like breast cancer cells are able to degrade type IV collagen
      intracellularly, suggesting that this is an important pathway for matrix
      degradation.

PMID- 11517932
TI  - High level synthesis of recombinant soluble urokinase receptor (CD87) by ovarian
      cancer cells reduces intraperitoneal tumor growth and spread in nude mice.
AB  - Focussing of the serine protease urokinase (uPA) to the tumor cell surface via
      interaction with its receptor (uPAR) is an important step in tumor invasion and
      metastasis. The human ovarian cancer cell line OV-MZ-6#8 was stably transfected
      with expression plasmids either encoding cell-associated uPAR (GPI-uPAR) or a
      soluble form of uPAR (suPAR) lacking its glycan lipid anchor. In vitro, high
      level synthesis of functionally active recombinant suPAR inhibited cell
      proliferation and led to reduced cell-associated fibrin matrix degradation,
      whereas fibrinolytic activity was increased in OV-MZ-6#8 cells overexpressing GPI
      uPAR. Both OV-MZ-6#8-derived clones were inoculated into the peritoneum of nude
      mice and tested for tumor growth and spread. High level synthesis of recombinant
      suPAR (without altering the physiological expression levels of GPI-uPAR and uPA
      in these cells) resulted in a significant reduction of tumor burden (up to 86%)
      in the xenogeneic mouse model. In contrast, overexpression of GPI-uPAR in tumor
      cells did not affect tumor growth. Our results demonstrate that high levels of
      suPAR in the ovarian cancer cell vicinity can act as a potent scavenger for uPA,
      thereby significantly reducing tumor cell growth and cancer progression in vivo.

PMID- 11517933
TI  - Immunochemical localisation of cathepsin S, cathepsin L and MHC class II
      associated p41 isoform of invariant chain in human lymph node tissue.
AB  - Antigen presentation by MHC class II molecules requires cysteine proteases (CP)
      for two convergent proteolytic processes: stepwise degradation of the invariant
      chain (Ii) and generation of immunogenic peptides. Their activity is controlled
      by intracellular CP inhibitors, including presumably the p41 isoform of invariant
      chain (p41 Ii), which is in vitro a potent inhibitor of cathepsin L but not of
      cathepsin S. In order to evaluate the inhibitory potential of p41 Ii in antigen
      presenting cells (APC), these three proteins were stained in lymph node tissue
      using specific monoclonal and polyclonal antibodies. The most abundant labelling
      was observed in subcapsular (cortical) and trabecular sinuses of the lymph node.
      In this area the most frequent APC were macrophages, as confirmed by the CD68
      cell marker. Using confocal fluorescence microscopy, co-localisation of p41 Ii
      with cathepsin S, but not with cathepsin L was found in these cells. Our results
      are consistent with the hypothesis that cathepsin S participates in degradation
      of the invariant chain, but they do not support the association between cathepsin
      L and p41 Ii in APC.

PMID- 11517934
TI  - Cathepsin B/cystatin C complex levels in sera from patients with lung and
      colorectal cancer.
AB  - A sandwich-type ELISA has been developed for quantification of the complex
      between the cysteine proteinase cathepsin B (CB) and its reversible tight-binding
      inhibitor cystatin C (CC) in normal and pathological sera. The assay is based on
      a combination of catching Ab (3E1), raised against CB, and a horseradish
      peroxidase-labelled detection Ab (1A2), raised against CC. Only the CB/CC complex
      is able to evoke a signal in this assay. The detection limit of the assay was
      15.5 nM and the working range between 31.3-200 nM. The within and between-run
      coefficients of variance (CV) varied from 4.7% to 9.4% and 11% to 12.8%,
      respectively, demonstrating satisfactory reproducibility of the method. The
      concentration of the CB/CC complex was determined in sera from 90 healthy
      controls, 32 patients with non-cancerous lung diseases, 148 patients with lung
      and 32 patients with colorectal cancer. The CB/CC complex was significantly less
      abundant in sera of patients bearing malignant lung tumours than in those with
      non-cancerous lung diseases or healthy controls (p<0.001). In colorectal cancer
      sera its level was significantly lower in advanced stages C and D than in early
      Dukes' stages A and B (p=0.02). Our results show that the increased levels of CB
      in malignant sera are not impaired effectively by CC and support the hypothesis
      of hindered inhibitory capability during cancer progression.

PMID- 11517935
TI  - Cathepsin L, but not cathepsin B, is a potential kininogenase.
AB  - Although papain-like enzymes are strongly inhibited by their natural tight
      binding inhibitors of the cystatin superfamily, cathepsins B and L may still
      retain some residual proteolytic activity toward Z-Phe-Arg-AMC in the presence of
      an excess of kininogen. This activity is abolished by adding E-64 or chicken
      cystatin. Cathepsins B and L show a single band of gelatinolytic activity when
      subjected to gelatin-SDS-PAGE. Adding high Mr kininogen, low Mr kininogen, T
      kininogen, or chicken cystatin to cathepsin L results in additional intense bands
      of enzyme activity corresponding to the protease-inhibitor complexes. Cathepsin B
      does not produce these additional bands. This gelatinolytic activity was
      inhibited by E-64, but not by EDTA, PMSF or Pefabloc. Cathepsin L also
      specifically generated kinins from high and low molecular weight kininogens in
      vitro, but cathepsin B did not. T-kininogen did not release any immunoreactive
      kinins when complexed with cathepsin L, as previously observed using tissue
      kallikreins. The ability of cathepsin L to generate vasoactive peptides raises
      the question of the physiological significance of this mechanism during
      inflammation.

PMID- 11517936
TI  - Arg-gingipain is responsible for the degradation of cell adhesion molecules of
      human gingival fibroblasts and their death induced by Porphyromonas gingivalis.
AB  - Arg-gingipain (Rgp) and Lys-gingipain (Kgp) are two major cysteine proteinases
      produced by the oral anaerobic bacterium Porphyromonas gingivalis, which has been
      shown to act as major pathogen in the development and progression of periodontal
      diseases. These enzymes are also important for this organism to proliferate and
      survive in periodontal pockets. Here we show that Rgp is responsible for the
      disruption of fibronectin-integrin interactions in human gingival fibroblasts by
      P. gingivalis. Fibroblasts incubated with the culture supernatant of P.
      gingivalis showed a time-dependent loss of the adhesion activity. Sodium dodecyl
      sulfate polyacrylamide gel electrophoresis and immunoblotting revealed that
      fibronectin and integrin subunits alpha2, beta1 and beta3 in the fibroblast
      culture largely disappeared with the treatment. The detached cells became
      committed to death by disruption of contacts between adhesion molecules. In
      contrast, the culture supernatants from the Rgp-deficient mutants produced no
      significant changes in either cell adhesion or viability. Prior treatment of the
      culture supernatant of P. gingivalis with an Rgp inhibitor, but not a Kgp
      inhibitor, strongly inhibited the detachment of fibroblasts followed by cell
      death. These results suggest that Rgp disrupts the integrin-fibronectin
      interactions in fibroblasts, thereby contributing to the damage of periodontal
      tissues in periodontal diseases caused by P. gingivalis.

PMID- 11517937
TI  - Neutrophil degranulation induced by Haemophilus ducreyi.
AB  - Haemophilus ducreyi is the causative bacterium of genital ulcers, which are
      collectively known as chancroid. Little is known about the cytotoxicity of H.
      ducreyi. The virulent strains are relatively resistant to phagocytosis and
      apoptosis by neutrophils. Therefore, experiments were designed to examine whether
      neutrophil degranulation caused by H. ducrey would provide insights into the
      virulence mechanisms through which cellular damage is affected by the organism.
      Clinical isolates of eight strains of H. ducreyi and the culture strain type
      CIP542 (Collection Institute Pasteur) were incubated with neutrophils harvested
      from human donor blood. The release by the organism of lysosomal enzymes from
      intracellular granules of neutrophils was indicative of degranulation. The
      results showed that H. ducreyi triggered the release of lysosomal enzymes from
      human neutrophils, and that the magnitude of the release was dependent both on
      the ratio of bacteria to neutrophils and the duration of incubation. In vitro
      experiments involving HeLa cells were designed to determine the manner in which
      H. ducreyi initiated the process of degranulation. The morphological changes
      associated with degranulation were visualized by confocal and transmission
      electron microscopy. This is the first report that describes degranulation of
      neutrophils induced by H. ducreyi which causes chancroid infection.

PMID- 11517938
TI  - Role of calpain in human sperm activated by progesterone for fertilization.
AB  - We evaluated the activation of mu-calpain in progesterone-activated human sperm.
      Semen collected from fertile donors with informed consent was liquefied and
      subjected to percoll gradient centrifugation. After exposure to different
      concentrations of progesterone, the samples were used for immunostaining, SDS
      PAGE and Western blot analysis. An increase of the intracellular free calcium
      concentration in the sperm following the addition of progesterone was observed
      using fura-2 AM. Immunostaining using an antibody against active mu-calpain
      produced 6 distinct staining patterns: (1) the acrosome, (2) an equatorial
      segment, (3) the whole head, (4) the neck, (5) the neck and tail or (6) unstained
      sperm. After addition of progesterone, the predominant type changed from the neck
      type (90%) to the neck and tail type (79%). Western blot analysis using a pro-mu
      calpain and a mu-calpain domain III antibody revealed autodigestion of mu
      calpain, indicating activation by progesterone. Using calpain-specific inhibitors
      it was shown that calpain activation contributes to sperm motility as well as to
      the acrosome reaction. These results suggest the possibility that activation of
      mu-calpain in human sperm by progesterone plays an important role in
      fertilization.

PMID- 11517939
TI  - Cathepsins X and B display distinct activity profiles that can be exploited for
      inhibitor design.
AB  - The carboxypeptidase and endopeptidase activities of cathepsins X and B, as well
      as their inhibition by E-64 derivatives, have been investigated in detail and
      compared. The results clearly demonstrate that cathepsins X and B do not share
      similar activity profiles against substrates and inhibitors. Using quenched
      fluorogenic substrates, we show that cathepsin X preferentially cleaves
      substrates through a monopeptidyl carboxypeptidase pathway, while cathepsin B
      displays a preference for the dipeptidyl pathway. The preference for one or the
      other pathway is about the same for both enzymes, i. e. approximately 2 orders of
      magnitude. Cleavage of a C-terminal dipeptide of a substrate by cathepsin X can
      be observed under conditions that preclude efficient monopeptidyl
      carboxypeptidase activity. In addition, an inhibitor designed to exploit the
      unique structural features responsible for the carboxypeptidase activity of
      cathepsin X has been synthesized and tested against cathepsins X, B and L.
      Although of moderate potency, this E-64 derivative is the first reported example
      of a cathepsin X-specific inhibitor. By comparison, CA074 was found to inactivate
      cathepsin B at least 34000-fold more efficiently than cathepsin X.

PMID- 11517940
TI  - Structure of cruzipain/cruzain inhibitors isolated from Bauhinia bauhinioides
      seeds.
AB  - The saline extract of Bauhinia bauhinioides dry seeds was shown to inhibit
      cruzipain, a cysteine proteinase from Trypanosoma cruzi. The inhibitory activity
      was assigned to a protein with 164 amino acid residues and molecular mass of 18
      034 Da that was purified by chromatography on DEAE-Sephadex, trypsin-Sepharose
      (removal of trypsin inhibitors), Mono Q and a reversed-phase C4 column. The
      primary structure is homologous to other plant Kunitz-type inhibitors, but it
      lacks cysteine residues and therefore the disulfide bridges. No methionine
      residue was identified by amino acid sequencing. The inhibition of cruzipain fits
      into a slow-tight binding mechanism with a low dissociation constant (Ki 1.2 nM).
      The studied Bauhinia protein also inhibits cruzain (Ki 0.3 nM), a C-terminally
      truncated recombinant species of cruzipain. Cathepsin L, a cysteine proteinase
      with high homology to cruzipain, is also inhibited (Ki 0.22 nM), but not
      cathepsin B, papain, bromelain or ficin.

PMID- 11517941
TI  - Invasion of ras-transformed breast epithelial cells depends on the proteolytic
      activity of cysteine and aspartic proteinases.
AB  - It has been suggested that the lysosomal proteinases cathepsin B, L and D
      participate in tumour invasion and metastasis. Whereas for cathepsins B and L the
      role of active enzyme in invasion processes has been confirmed, cathepsin D was
      suggested to support tumour progression via its pro-peptide, rather than by its
      proteolytic activity. In this study we have compared the presence of active
      cathepsins B, L and D in ras-transformed human breast epithelial cells (MCF-10A
      neoT) with their ability to invade matrigel. In this cell line high expression of
      all three cathepsins was detected by immunofluorescence microscopy. The effect of
      proteolytic activity on cell invasion was studied by adding various natural and
      synthetic cysteine and aspartic proteinase inhibitors. The most effective
      compound was chicken cystatin, a general natural inhibitor of cysteine
      proteinases, (82.8+/-1.6% inhibition of cell invasion), followed by the synthetic
      inhibitor trans-epoxysuccinyl-L-leucylamido-(4-guanidino) butane (E-64). CLIK
      148, a specific inhibitor of cathepsin L, showed a lower effect than chicken
      cystatin and E-64. Pepstatin A weakly inhibited invasion, whereas the same molar
      concentrations of squash aspartic proteinase (SQAPI)-like inhibitor, isolated
      from squash Cucurbita pepo, showed significant inhibition (65.7+/-1.8%). We
      conclude that both cysteine and aspartic proteinase activities are needed for
      invasion by MCF-10A neoT cells in vitro.

PMID- 11517942
TI  - Folding incompetence of cathepsin L-like cysteine proteases may be compensated by
      the highly conserved, domain-building N-terminal extension of the proregion.
AB  - Folding of cathepsins L and S depend upon their proregion which extends the
      enzyme part by about 100 amino acids. Only a minority of the prosequence follows
      the structural template provided by the enzyme part; the majority forms an
      autonomous minidomain fairly distant from the active site cleft. We suggest that
      this prodomain may be the structural correlate of a foldase function of the
      proregion within the cathepsin L-like subfamily of papain-type cysteine proteases
      and report on a functional approach supporting this hypothesis.

PMID- 11517943
TI  - Anti-cathepsin L monoclonal antibodies that distinguish cathepsin L from
      cathepsin V.
AB  - Cathepsin L is a lysosomal cysteine protease involved in intracellular protein
      degradation. Recently, several new cysteine proteases have been identified. Human
      cathepsin V, a thymus- and testis-specific human cysteine protease, shares 78%
      sequence identity with human cathepsin L. Due to the strong sequence similarity,
      highly selective reagents are needed to elucidate the physiological functions of
      the two enzymes. Monoclonal antibodies (mAbs) have been prepared against
      recombinant human cathepsin L. Antibodies produced by five clones reacted with
      procathepsin L and mature cathepsin L. They also reacted with cathepsin L in
      complex with a peptide fragment, which is identical to the alternatively spliced
      segment of the p41 form of MHC Class II associated invariant chain. Two mAbs,
      (M105 and H102) were specific for cathepsin L, while three (N135, B145 and D24)
      cross-reacted with cathepsin V. None of the mAbs cross-reacted with cathepsins B,
      H and S. We have developed a sandwich enzyme-linked immunosorbent assay (ELISA)
      for quantifying cathepsin L. This sandwich ELISA uses a combination of two
      monoclonal antibodies which recognize different, non-overlapping epitopes on the
      cathepsin L molecule. The lower detection limit of the sandwich ELISA was 5 ng of
      cathepsin L per ml.

PMID- 11517944
TI  - Properties of a milk clotting protease isolated from fruits of Bromelia balansae
      Mez.
AB  - Unripe fruit extracts of Bromelia balansae Mez (Bromeliaceae), whose principal
      endopeptidase is balansain I (isolated for anion exchange chromatography: pI =
      5.45, molecular weight = 23192), exhibit a pH profile with a maximum activity
      around pH 9.0 and are inhibited only by cysteine peptidases inhibitors. The
      alanine and glutamine derivatives of N-alpha-carbobenzoxy-L-amino acid p
      nitrophenyl esters were strongly preferred by the enzyme. Enzymatic hydrolysis of
      milk and soy proteins yield characteristic patterns at pH 9.0. The N-terminal
      sequence showed a very high homology (85-90%) with other known Bromeliaceae
      endopeptidases.

PMID- 11517945
TI  - Comparison of two cysteine endopeptidases from Pseudananas macrodontes (Morr.)
      Harms (Bromeliaceae).
AB  - The properties of two cysteine peptidases (macrodontain I and II) isolated from
      fruits of Pseudananas macrodontes have been compared. The enzymes showed optimum
      pH ranges near neutrality and were inhibited by E-64 and other cysteine peptidase
      inhibitors. Molecular masses were 23459 and 23703 kDa, the isoelectric points
      were 6.1 and 5.9, and the Km values were 13.4 and 8.9 microM (Bz-Phe-Val-Arg-AMC)
      for macrodontain I and II, respectively. N-alpha-CBZ-L-amino acid p-nitrophenyl
      esters were tested for both enzymes. The N-terminal sequences of both proteases
      differed slightly and showed high sequence similarity to other pineapple stem
      derived cysteine endopeptidases.

PMID- 11517946
TI  - Comparison of two cysteine endopeptidases from latices of Morrenia brachystephana
      Griseb. and Morrenia odorata (Hook et Arn.) Lindley (Asclepiadaceae).
AB  - The properties of morrenain b II, a proteinase isolated from the latex of
      Morrenia brachystephana, were compared with those of morrenain o II, a proteinase
      obtained from the latex of Morrenia odorata. Both peptidases were purified to
      homogeneity by acetone precipitation followed by cation exchange chromatography.
      The enzymes have pI values higher than 9.3 and similar molecular masses (close to
      26 kDa) as determined by SDS-PAGE. They display maximum proteolytic activity
      within an alkaline pH range, and also exhibit esterolytic activity. The N
      terminal sequences of morrenain o II and morrenain b II show a high degree of
      homology between each other and to other cysteine plant proteinases.

PMID- 11517947
TI  - Polymorphisms in the bradykinin B2 receptor gene and childhood asthma.
AB  - Bradykinin has been suggested as one of the key mediators of bronchial asthma.
      Polymorphisms with a potential functional relevance have been described in the B2
      bradykinin receptor gene. Study of these polymorphisms in 77 children with asthma
      and 73 controls revealed no association. However, when comparing the asthmatics
      according to their age at onset (before and after age 4), the exon 1 allele BE1
      2G was significantly associated with late-onset asthma (p<0.05). Since BE1-2G has
      previously been shown to lead to a higher transcription rate of the B2 receptor,
      this result warrants further investigation of the role of bradykinin in
      conferring susceptibility to pediatric asthma.

PMID- 11517948
TI  - Images in   cardiology.

PMID- 11517949
TI  - Infantile colic and chiropractic spinal manipulation.

PMID- 11517950
TI  - Diluted treatment effects?

PMID- 11517951
TI  - Commentaries--read with caution!

PMID- 11517952
TI  - Alcopops are not responsible for acute paediatric attendances with alcohol
      intoxication.

PMID- 11517953
TI  - Other implications of disposable nappies.

PMID- 11517954
TI  - Dexamethasone, survival, and neurological impairment.

PMID- 11517955
TI  - Childhood diabetes towards the 21st century.

PMID- 11517956
TI  - Effect of long-term recombinant growth hormone therapy in children--the National
      Cooperative Growth Study, USA, 1985-1994.
AB  - Over a 9-year period (1985-1994) approximately 20,000 children received
      recombinant human growth hormone (rhGH) while enrolled in the National
      Cooperative Growth Study (NCGS), an observational, longitudinal study designed to
      monitor the long term efficacy and safety of rhGH administered to children in
      North America. Forty-four percent of the patients had idiopathic growth hormone
      deficiency (IGHD), 13.8% organic GHD (OGHD), 25% idiopathic short stature (ISS),
      9.9% Turner's syndrome (TS), and 7.3% miscellaneous disorders. Eighty-five
      percent of the patients enrolled were Caucasian, and approximately two-thirds of
      the non-Turner patients were male. For the subset of patients treated for at
      least 4 years and who were prepubertal throughout this period (IGHD N=308, OGHD
      N=93, ISS N=169, TS N=82), mean growth rates increased in all patient categories
      and remained at or above pretreatment growth rates through 4 consecutive years of
      therapy with rhGH. Growth rates during administration of rhGH were greater in
      children in whom the pretreatment maximum stimulated GH concentration was < or =3
      microg/l. Patients treated with 6 or 7 doses of rhGH each week grew more rapidly
      than did those receiving thrice weekly dosages, although the ratios of the
      increment in bone age to the increment in height age after two years of therapy
      were similar in the two treatment regimens. For patients treated with rhGH for 7
      consecutive years, the mean height standard deviation scores increased by 2.5 in
      IGHD (N=169), 2.0 in OGHD (N=50), 1.9 in ISS (N=69), and 1.3 in TS (N=19), but
      remained below target heights in all categories. It is concluded that
      administration of rhGH increases growth rates in patients with IGHD, OGHD, ISS,
      and TS, and that this stimulatory effect can persist for at least 4 years.

PMID- 11517957
TI  - Decreased lumbar spine bone mass and low bone turnover in children and
      adolescents with insulin dependent diabetes mellitus followed longitudinally.
AB  - The effects of insulin dependent diabetes mellitus (IDDM) on bone metabolism are
      still not well defined. We evaluated total bone mineral content (TBMC) and bone
      mineral density (BMD) at the lumbar spine and femoral neck using dual X-ray
      absorptiometry in 26 IDDM children (15 M, 11 F) with a mean chronological age of
      12.1+/-3.1 yr (range 7.1-14.2 yr). Duration of diabetes was 4.3+/-2.9 yr, with a
      mean glycosylated hemoglobin of 9.2+/-0.4%. BMD and TBMC standard deviation
      scores (Z-scores) were determined by comparing our results to controls matched
      for age, sex and pubertal status. BMD and bone formation and resorption markers
      were determined at the beginning of the study and after one year of follow up.
      Mean lumbar spine Z-score was -1.06+/-0.2, with negative values in 24 of 26
      children (92.6%); 14/26 patients (53.8%) had a lumbar spine Z-score >1.0 SD below
      the mean. Mean lumbar spine Z-score remained unchanged after one year of follow
      up (-1.02+/-0.3). No significant differences were obtained in femoral neck BMD or
      TBMC between groups. No correlation was observed between lumbar spine BMD Z
      scores and duration of IDDM or degree of diabetes control, as assessed by the
      mean glycosylated hemoglobin. Daily urinary calcium excretion was elevated in our
      patients initially and after one year of follow up; however, no correlation was
      obtained between lumbar spine BMD and 24 h urinary calcium excretion. Carboxy
      terminal propeptide of type 1 collagen values and levels of urinary cross-linked
      N-telopeptides of type 1 collagen in the diabetic children were significantly
      lower than those of the matched controls. Osteoblastic activity as assessed by
      serum osteocalcin and by the carboxy-terminal propeptide of type I collagen and
      bone resorption as measured by cross-linked N-telopeptides of type 1 collagen did
      not correlate with the lumbar spine Z-scores. When IDDM patients were subdivided
      into males and females and into children with more than or less than 2 yr
      duration of diabetes since diagnosis, no differences between groups were found.
      These results suggest that insulin dependent diabetes in children is associated
      with low bone turnover resulting in a deficit in bone mass which may be
      manifested as osteopenia in the growing bone. This defect is already present in
      trabecular bone early on in the disease and seems not to be related to glycemic
      control.

PMID- 11517958
TI  - Puberty and mineralization of the skeleton in girls.
AB  - We studied the acquisition of bone mineral and related changes in body mass,
      pubertal status, and sex hormones in 75 healthy prepubertal and pubertal girls
      aged 7.5-16 years. Bone mineral density of the lumbar spine (L-1, L-2, L-3, L-4)
      was measured in children by quantitative computerized tomography. Skeletal
      mineralization accelerated markedly at puberty. Age, weight, height, and body
      mass index (BMI) were highly correlated with bone mineral density.

PMID- 11517959
TI  - The effects of pubertal status and glycemic control on the growth hormone-IGF-I
      axis in boys with insulin-dependent diabetes mellitus.
AB  - Dysregulation of the growth hormone (GH)-insulin-like growth factor-I (IGF-I)
      axis in children and adolescents with insulin-dependent diabetes mellitus (IDDM)
      is well documented. Elevated levels of circulating GH, increased GH secretory
      amplitude, and decreased concentrations of IGF-I, IGFBP-3, and GHBP have been
      related to poor glycemic control. We proposed that pubertal maturation may be a
      more significant factor, potentially overriding the effects of metabolic control,
      especially during mid-puberty when the GH-IGF-I axis is maximally stimulated. We
      studied 24 male children and adolescents with IDDM over a 5 year period. Subjects
      were grouped both by pubertal stage (prepubertal vs mid-pubertal) and by level of
      glycemic control (hemoglobin A1 (<9%, 9-11.5%, and >11.5%). Twenty-four hour
      every 20 minute blood sampling for GH determination was analyzed using the
      Cluster algorithm, and static measures of IGF-I, IGFBP-3, and GHBP were obtained.
      When analyzed by pubertal status, we found no difference in the number of GH
      secretory peaks or the interval between concentration peaks. The sum of the peak
      heights and area under the curve were significantly greater in the mid-pubertal
      boys, as was the average GH nadir. Serum levels of IGF-I and IGFBP-3 were greater
      in the mid-pubertal boys, but levels of GHBP were higher in the prepubertal boys.
      When analyzed by level of glycemic control, we found no differences in the number
      of GH secretory peaks or interval between peaks among the 3 groups. However, the
      sum of the peak heights, area under the curve, and average GH nadir were all
      lower in the group with the intermediate level of glycemic control (HgbA1 9
      11.5%); no differences were observed between the other 2 groups. This
      relationship persisted when the mid-pubertal subjects were analyzed separately.
      No differences were found among the 3 groups for levels of IGF-I, IGFBP-3, or
      GHBP. We conclude that normal increases in GH secretion and levels of IGF-I and
      IGFBP-3 occur during mid-puberty in boys with IDDM. A concomitant increase in
      average GH nadir may reflect an underlying effect of metabolic control. Greater
      GH secretion was observed in the groups with the lowest and highest levels of
      glycemic control. We speculate that this may be related to an increased incidence
      of severe hypoglycemic episodes in the group with the lowest levels of
      glycosylated hemoglobin, resulting in metabolic derangements similar to those
      with elevated glycosylated hemoglobin levels.

PMID- 11517960
TI  - Urinary free cortisol and its nyctohemeral variation in adolescents and young
      adults with IDDM: relation to endothelin 1 and indices of diabetic angiopathy.
AB  - The existence of a hyperactive hypothalamic pituitary adrenal (HPA) axis in
      diabetics and its relevance to diabetic complications has been controversial. In
      this study we determined the 24 hour urinary excretion of free cortisol (UFC),
      its nyctohemeral variation and its relation to indices of diabetic angiopathy. In
      130 subjects with IDDM, aged 15.2+/-4.8 years and diabetes duration 7.3+/-5
      years, and in 48 controls of comparable age, UFC, urinary endothelin (UET1),
      urinary albumin, HbA1c, and plasma renin were determined. The total 24-hour UFC
      excretion was greater in diabetics than in controls (p=0.002) and also greater in
      diabetic males than in females (p=0.006), while no sex difference was detected in
      the controls. Day UFC excretion was greater than night UFC excretion (p<0.001) in
      all subjects. UFC correlated to carotid intimal plus medial thickness (r=0.48,
      p=0.002), urinary albumin (r=0.50, p<0.001), UET1 (r=0.56, p<0.001), diastolic,
      systolic and mean blood pressure (r=0.27, p=0.003; r=0.41, p<0.001; r=0.34,
      p<0.001), BMI (r=0.50, p<0.001), serum creatinine (r=0.35, p<0.001), total
      cholesterol (r= -0.19, p=0.036), HDL (r= -0.22, p=0.038), LDL (r= -0.23,
      p=0.032), age (r=0.61, p<0.001) and diabetes duration (r=0.37, p<0.001). These
      results suggest that hyperactivity of the HPA axis or of the adrenals, due to
      chronic stress, hypoglycemic episodes or other factors, possibly contributes to
      the establishment or progression of diabetic micro- or macroangiopathy.

PMID- 11517961
TI  - Incidence of insulin dependent diabetes mellitus in children 0-14 years old in
      the Veneto Region, Italy.
AB  - The objective of this study was to provide reliable data on the incidence of type
      1 diabetes, in children aged 0-14 years, in the Veneto region, and to better
      understand its geographical variability throughout Italy and Europe. All new
      cases of type 1 diabetes diagnosed between 1st January 1993 and 31st December
      1994 among residents in Veneto were recorded. Clinical records from 33 hospitals
      in the region were used as the primary source for this study. The number of
      disease-related free-of-charge prescriptions served as a secondary source. The
      completeness of ascertainment was estimated at 89%. The mean incidence estimated
      over the 1993-1994 period was 10.7 per 100,000/year. The Veneto region appears to
      have a relatively high incidence of IDDM among non-insular Italian regions. No
      significant sex-related difference in incidence was noted; the male/female ratio
      was 1.5.

PMID- 11517962
TI  - Insulin-like growth factor axis parameters in sick hospitalized neonates.
AB  - The circulating insulin-like growth factor (IGF) axis consists of the IGF
      peptides, the IGF binding proteins (IGFBPs), and the IGFBP proteases. Little is
      known about the IGF axis in newborns, its possible perturbations in sick
      neonates, and the effect of nutrition on the IGF axis of such patients. The aims
      of this study were to define IGF axis parameters in the sera of hospitalized
      newborns and to correlate these parameters with the nutritional status of the
      infants. Serum samples obtained from twenty four hospitalized infants in the
      intensive care nursery were analyzed for IGF axis parameters. Insulin-like growth
      factor-I and IGFBP-3 by RIA were mostly within the normal range for age and were
      only minimally affected by gestational age. In comparison, 8 newborn infants with
      congenital growth hormone deficiency had IGFBP-3 levels which were below the
      normal range. Two infants on ECMO had elevated levels of IGFBP-3 by RIA. Western
      ligand blotting (WLB) demonstrated that IGFBP-2 was the major binding protein in
      infant serum and the 44 kDa IGFBP-3 in critically ill neonatal serum was
      approximately 10% of adult serum levels. IGFBP-3 by RIA in neonatal serum
      averaged approximately 25% of adult serum levels. Compatible with this
      discrepancy, a number of sick neonates had detectable levels of IGFBP-3
      proteolytic activity and higher levels of IGFBP-3 fragments compared to normal
      adult serum in both the protease assays and Western immunoblotting. There was no
      correlation between any IGF axis parameter and nutritional status. In summary,
      sick hospitalized neonates display mostly normal IGF and IGFBP-3 levels, which
      are not correlated to nutritional intake. Thus serum IGFBP-3 levels maintain
      their diagnostic utility for growth hormone deficiency in critically ill
      neonates.

PMID- 11517963
TI  - Lack of seasonality in the month of onset of childhood IDDM (0.7-15 years) in
      Shanghai, China.
AB  - A cohort of 136 children from Shanghai with insulin dependent diabetes mellitus
      (IDDM) (0.7-15 years) were analyzed for the month of onset of disease and month
      of birth. In contradistinction to populations with a medium or high incidence of
      IDDM, no seasonality was registered in the month of onset. On the other hand
      there was a significant (p < 0.026) seasonality in the month of birth (peak
      November to January), but which differed in pattern to that observed in
      populations with medium or high incidence. Our findings support the hypothesis
      that the initiation of IDDM is due to a viral infection and that one cause for
      the low incidence of childhood IDDM in certain populations is immunization
      against infectious pathogens in their early life.

PMID- 11517964
TI  - Detection of Gly-196-Ser mutation in 5alpha-reductase type II gene in a Brazilian
      patient with female assignment and behavior.
AB  - We describe the identification of a single base mutation in the 5alpha-reductase
      type II gene in a Brazilian patient who was reared as female and remained with
      female behavior and sexual identity.

PMID- 11517965
TI  - A young boy with a thyroid yo-yo.
AB  - We describe a boy with Hashimoto's thyroiditis and Addison's disease who was
      initially hypothyroid, developed hyperthyroidism and eventually became euthyroid.
      A rise and fall in thyroid binding inhibitory immunoglobulin and thyroid
      stimulating antibodies were demonstrated to have correlated with the appropriate
      changes in thyroid status. The fact that Hashimoto's thyroiditis can evolve in
      such a way emphasizes the importance of lifetime follow-up in these patients.

PMID- 11517966
TI  - Increased urinary excretion of pyridinoline and deoxypyridinoline in a girl with
      congenital contractural arachnodactyly.
AB  - Congenital contractural arachnodactyly (CCA) is caused by mutations in the gene
      for fibrillin 2 glycoprotein, a component of connective tissue. The causes of
      osteodystrophy or osteodysplasia in CCA are unknown. We report bone metabolism in
      a 28 month-old girl with CCA. Serum alkaline phosphatase and osteocalcin levels
      were 650 IU/l and 22 ng/ml at 1.5 months old (control: 530+/-65, 16.5+/-4.3), and
      580 IU/l and 21 ng/ml at 28 months old (control: 465+/-58, 15.0+/-3.5), i.e. in
      upper-normal levels. The urinary pyridinoline and deoxypyridinoline levels were
      1176 and 194 micromol/mol creatinine at 1.5 months old (control: 329+/-76, 63+/
      12), and 407 and 111 micromol/mol cr at 28 months old (control: 231+/-49, 50+/
      11), apparently higher than the control values. These findings may indicate that
      abnormal fibrillin may impair bone metabolism and cause the osteodystrophy or
      osteodysplasia in CCA.

PMID- 11517967
TI  - Dr. Verrotti's and colleagues' response to our letter repeated a number of errors
      and added new ones.

PMID- 11517968
TI  - Different distribution of c-myc and MIB-1 positive cells in malignant meningiomas
      with reference to TGFs, PDGF, and PgR expression.
AB  - We investigated the expression of transforming growth factors (TGFs), platelet
      derived growth factor (PDGF), progesterone receptor (PgR), and c-myc in 20 cases
      of meningioma of various grades: 17 benign, 2 atypical, and 1 anaplastic. All
      cases of atypical and anaplastic meningioma were positive for c-myc, whereas all
      17 benign meningiomas were negative for c-myc immunostaining. Expression of TGF
      alpha, TGF-beta, and PDGF-BB proteins was seen in more than 80% of the meningioma
      cases and was not restricted to their histological grade of meningioma. PgR was
      expressed mainly in benign meningiomas. Moreover, the cells expressing c-myc
      protein were not usually stained by MIB-1. These results indicate that c-myc does
      not directly work on the proliferation of meningioma cells, and even in
      homogeneous meningioma cells, there may be many functional variations that lead
      the meningioma cells to their growth.

PMID- 11517969
TI  - Analysis of interleukin-6 gene expression in primary human gliomas, glioblastoma
      xenografts, and glioblastoma cell lines.
AB  - Our previous study showed that high-grade astrocytomas often expressed high
      interleukin (IL)-1beta production. Coexpression of IL-1beta and IL-6 has been
      found in a number of glioma samples and glioma cell lines. To characterize the
      expression of IL-6 in the human glioma microenvironment, we investigated
      surgically excised human gliomas, human glioblastoma xenografts, and human
      glioblastoma cell lines using the reverse transcriptase-polymerase chain reaction
      (RT-PCR), immunohistochemistry (IHC), and enzyme-linked immunosorbent assay
      (ELISA). In the 29 primary gliomas, transcripts of IL-6 were less frequently
      detectable (55.6%) than those of IL-1beta (72.4%) or those of IL-10, IL-8, or IL
      1alpha (>80% each). As for IL-6 gene expression, little or no transcription was
      observed in low-grade astrocytomas, oligodendroglial tumors, and 1 ependymoma.
      Strong IL-6 gene expression was found in only 5 of 9 glioblastomas.
      Immunohistochemically, IL-6 antigen was localized in the tumor cells and
      macrophages in 4 of 7 glioblastomas. In 3 glioblastomas transplanted into nude
      mice, both IL-1beta and IL-6 were detected only in 1, but othercytokines (IL-8,
      IL-10, and IL-1alpha) were detected in all 3 xenografts by RT-PCR. Two cell lines
      both showed IL-6 expression at the mRNA level, and in a cell line with a high
      level of IL-6 and IL-1beta transcripts, significant production of IL-6 was
      observed by IHC and ELISA. We concluded that IL-6 produced in tumor tissue may be
      involved in tumor progression in some glioblastomas, but not in low-grade
      astrocytomas and oligodendroglial tumors, and that IL-6 gene expression is
      closely correlated with IL-1beta expression in biopsy tissue, xenografts, and
      cultures of human gliomas.

PMID- 11517970
TI  - Intratumoral microinfusion of nimustine (ACNU) for recurrent glioma.
AB  - We investigated stereotactic intratumoral microinfusion of nimustine (ACNU) in
      recurrent brain tumors. Eligibility required histologic confirmation of glioma
      recurrence despite standard radiotherapy and chemotherapy as well as enhancement
      of the recurrence with gadolinium on magnetic resonance imaging (MRI). A total
      intratumoral dose of 10 mg of ACNU was administered continuously with a
      microinfusion pump over an average of 13h. Fifteen infusions were given in nine
      patients. All patients completed the treatment safely. On MRI, necrotic changes
      surrounded the infusion area in all patients, and tumor progression was inhibited
      or performance score was improved in seven of nine patients. No symptomatic
      systemic toxicity was evident, although one patient developed permanent left
      oculomotor palsy locally after treatment of a left medial temporal tumor. It is
      concluded that direct microinfusion of ACNU into recurrent gliomas can induce
      tumor necrosis and inhibit tumor growth.

PMID- 11517971
TI  - Histogenesis and proliferative activity of central neurocytomas.

PMID- 11517972
TI  - Fas ligand expression and depletion of T-cell infiltration in astrocytic tumors.
AB  - Fas (APO-1/CD95) ligand (FasL) and its receptor, Fas, play a key role in the
      regulation of apoptosis in the immune system. FasL acts as a cytotoxic effector
      molecule to Fas-expressing malignant tumor cells; however, it has recently been
      suggested that FasL also acts as a possible mediator of tumor immune privilege.
      We studied FasL expression in glioblastoma cell lines and a series of human
      glioma specimens by Western blotting and immunohistochemistry. In addition,
      quantitative analysis of T-cell infiltration in these tumors was performed. FasL
      expression was seen in all cell lines and in 9 of 14 specimens by Western
      blotting and immunohistochemistry. The distribution of FasL was recognized in the
      cytoplasm of tumor cells (5 of 9) and in the vascular endothelium (4 of 9). Both
      types of FasL expression were associated with a significant reduction (p < 0.05)
      in T-cell infiltration when compared with FasL-negative areas within the same
      tumor or FasL-negative specimens. Since T-cell apoptosis could be induced by FasL
      expressing tumor cells, the present findings suggest that apoptosis induction by
      FasL expressed on tumor cells and/or vascular endothelium might be one mechanism
      for T-cell depletion in astrocytic tumor tissues.

PMID- 11517973
TI  - A case of solitary fibrous tumor of the meninges.
AB  - We report a rare case of solitary fibrous tumor (SFT) of the meninges of the
      posterior fossa presenting as an intracerebellar hemorrhage. A 29-year-old woman
      was admitted with sudden-onset severe headache, nausea, and vomiting. A computed
      tomographic (CT) scan of the brain revealed an intracerebellar hemorrhage 3.5cm
      in diameter. Gadolinium-enhanced magnetic resonance imaging (MRI) showed a
      heterogeneous enhancement mass. A posterior craniotomy found a firm, highly
      vascular tumor attached to the meninges. Histologically, the tumor showed mostly
      sclerotic tissues with spindle cells. In few areas, the tumor had a more compact
      arrangement of spindle-shaped cells with vascular spaces and highly cellular
      components. Immunohistochemical study revealed strong CD-34 immunopositivity in
      many tumor cells. The tumor was diagnosed as SFT of the meninges. We report the
      clinical and histological features of this newly described tumor with a
      heterogeneous component.

PMID- 11517974
TI  - Meningeal Rosai-Dorfman disease: report of three cases and literature review.
AB  - Rosai-Dorfman disease is a well-recognized clinicopathological entity, which in
      rare cases affects the central nervous system, where it mimics meningioma. We
      describe three cases and review the literature. Histological and
      immunohistochemical confirmation is essential for definitive diagnosis. In
      addition to emperipolesis (lymphophagocytosis), reactivity for S-100 and CD68 and
      nonreactivity for CD-la immunostaining are characteristic features of this
      histioproliferative disease. In contrast to meningioma, this tumor usually occurs
      in young males and infiltrates the brain parenchyma.

PMID- 11517975
TI  - A case of undifferentiated glioma in a 70-year-old woman.
AB  - The present case involved a 70-year-old woman who was diagnosed with a right
      cerebral hemorrhage. Excisional surgery of the hematoma was performed. Grossly, a
      whitish, solid tumor (1 x 1 x 0.8 cm in size) was recognized in the hematoma.
      Histologically, the tumor was composed of large, polygonal cells and small
      undifferentiated cells in a jumbled architectural arrangement with a cartilage
      component. The large, polygonal cell component was conspicuous and somewhat
      rhabdoid in appearance and appeared to be an astrocytic tumor showing glial
      differentiation. The small, undifferentiated cell component resembled tumor cells
      of a primitive neuroectodermal tumor (PNET). Clinical follow-up of the patient
      for 2 months after the first operation revealed recurrence with rapid growth. A
      second operation was performed, but the patient died 8 months after the first
      operation (2 months after the second). Immunohistochemically, the tumor cells
      suggesting glial differentiation were positive for glial fibrillary acidic
      protein (GFAP), S-100, neuron-specific enolase (NSE), and vimentin. PNET-like
      components in the primary tumor were positive for NSE, GFAP, and S-100, and
      weakly positive for vimentin and synaptophysin. Each tumor cell was negative for
      epithelial membrane antigen (EMA), keratin, desmin, actin, myoglobin,
      neurofilament (NF), and MIC2 protein. The recurrent tumor revealed predominantly
      PNET-like components; however, only a few tumor cells were positive for GFAP.
      This appearance suggested that this brain tumor might originate from a common
      multipotential stem cell. Considering its histopathological and
      immunohistochemical characteristics, the primary tumor was finally regarded as an
      undifferentiated glioma with dedifferentiation of the glial component in the
      recurrent tumor.

PMID- 11517976
TI  - Expression of hepatocyte growth factor and matrix metalloproteinase-2 in human
      glioma.
AB  - Hepatocyte growth factor (HGF) has a stimulatory effect on the synthesis of
      matrix metalloproteinase-2 (MMP-2), which is involved in glioma invasion. In this
      study, to clarify the correlation between the expression of HGF and MMP-2 in
      glioma tissues, immunohistochemical analysis of HGF and MMP-2 was performed in 11
      cases of astrocytoma, 10 cases of anaplastic astrocytoma, and 9 cases of
      glioblastoma. As a result, expression of HGF and MMP-2 was correlated with the
      grade of malignancy (P = 0.0181 and 0.0001, respectively), and a significant
      correlation between the immunoreactivity of HGF and that of MMP-2 was observed (P
      < 0.05). Immunofluorescence study revealed the concomitant expression of HGF and
      MMP-2 in glioma tissue. In cultured glioma cell lines (SNB-19, U87MG, and
      U373MG), exogenous recombinant HGF effectively acted on the production of the
      active and latent forms of MMP-2 protein in a dose-dependent manner. Active MMP-2
      increased more effectively than the latent form. Taken together, these results
      suggest that HGF may promote glioma invasion in vivo by production of MMP-2.

PMID- 11517977
TI  - DEFRA seeks comments on proposals to extend the role of veterinary nurses...and
      of trained technicians in equine dentistry.

PMID- 11517978
TI  - Veterinary surgeon suspended for failing to provide emergency cover.

PMID- 11517979
TI  - Relations between practice and government: defining the role of the LVI.

PMID- 11517980
TI  - No 'sinister agenda' behind dispensing review.

PMID- 11517981
TI  - Predictive spatial modelling of alternative control strategies for the foot-and
      mouth disease epidemic in Great Britain, 2001.
AB  - A spatial simulation model of foot-and-mouth disease was used in March and early
      April 2001 to evaluate alternative control policies for the 2001 epidemic in
      Great Britain. Control policies were those in operation from March 20, 2001, and
      comprised a ban on all animal movements from February 23, 2001, and a stamping
      out policy. Each simulation commenced with the known population of infected farms
      on April 10, 2001, and ran for 200 days. For the control policy which best
      approximated that actually implemented from late March, the model predicted an
      epidemic of approximately 1800 to 1900 affected farms, and estimated that the
      epidemic would be eradicated between July and October 2001, with a low
      probability of continuing beyond October 2001. This policy included the slaughter
      out of infected farms within 24 hours, slaughter of about 1.3 of the surrounding
      farms per infected farm within a further 48 hours, and minimal interfarm
      movements of susceptible animals. Delays in the slaughter of animals on infected
      farms beyond 24 hours after diagnosis slightly increased the epidemic size, and
      failure to achieve pre-emptive slaughter on an adequate number of at-risk farms
      substantially increased the expected size of the epidemic. Vaccination of up to
      three of the most outbreak-dense areas carried out in conjunction with the
      adopted control policy reduced the predicted size of the epidemic by less than
      100 farms. Vaccination of buffer zones (designed to apply available vaccine and
      manpower as effectively as possible) carried out in place of the adopted control
      policy allowed the disease to spread out of control, producing an epidemic
      involving over 6000 farms by October 2001, with no prospect of immediate
      eradication.

PMID- 11517982
TI  - Dissecting aneurysm of the carotid artery as a cause of respiratory distress in
      adult cattle.
AB  - A two-and-a-half-year-old Friesian cow and a five-year-old Charolais cow
      developed severe respiratory distress and palpable swellings to the left of the
      larynx as a result of a dissecting aneurysm of the common carotid artery. Neither
      cow responded to medical treatment. The underlying pathogenesis of the condition
      was uncertain, but direct trauma to the carotid artery was a possible
      contributory factor. Aneurysms of the common carotid artery should be considered
      when swelling occurs in the region of the larynx or when respiratory distress is
      due to laryngeal compression.

PMID- 11517983
TI  - Comparison of thiopentone/guaifenesin, ketamine/guaifenesin and
      ketamine/midazolam for the induction of horses to be anaesthetised with
      isoflurane.
AB  - Forty-eight horses subjected to elective surgery were randomly assigned to three
      groups of 16 horses. After premedication with 0.1 mg/kg acepromazine
      intramuscularly and 0.6 mg/kg xylazine intravenously, anaesthesia was induced
      either with 2 g thiopentone in 500 ml of a 10 per cent guaifenesin solution,
      given intravenously at a dose of 1 ml/kg (group TG), or with 100 mg/kg
      guaifenesin and 2.2 mg/kg ketamine given intravenously (group KG), or with 0.06
      mg/kg midazolam, and 2.2 mg/kg ketamine given intravenously (group KM).
      Anaesthesia was maintained with isoflurane. The mean (sd) end tidal isoflurane
      concentration (per cent) needed to maintain a light surgical anaesthesia (stage
      III, plane 2) was significantly lower in group KM (0.91 [0.03]) than in groups TG
      (1.11 [0.03]) and KG (1.14 [0.03]). The mean (sd) arterial pressure (mmHg) was
      significantly lower in group KG (67.4 [2.07]) than in groups TC (75.6 [2.23]) and
      KM (81.0 [2.16]). There were no significant differences in the logarithm of the
      heart rate, recovery time or quality of recovery between the three induction
      groups. However, pronounced ataxia was observed in the horses of group KM,
      especially after periods of anaesthesia lasting less than 75 minutes.

PMID- 11517984
TI  - Borna disease virus infection in FIV-positive cats in Germany.

PMID- 11517985
TI  - Inheritance of renal tubular dysplasia in Japanese Black cattle.

PMID- 11517986
TI  - Survival of Dermatophilus congolensis under laboratory conditions in Nigeria.

PMID- 11517987
TI  - Narcolepsy in a ram lamb.

PMID- 11517988
TI  - Control of FMD.

PMID- 11517989
TI  - Control of FMD.

PMID- 11517990
TI  - Private testing for FMD.

PMID- 11517991
TI  - Castration of horses and analgesia.

PMID- 11517992
TI  - Use, storage and supply of schedule 2 drugs.

PMID- 11517993
TI  - Use of pooled colostrum.

PMID- 11517994
TI  - Mouth ulcers in horses.

PMID- 11517995
TI  - Treatment of Alzheimer's disease with acetylcholinesterase inhibitors: bridging
      the gap between evidence and practice.
AB  - Views on drug therapy with acetylcholinesterase inhibitors of the cognitive
      symptoms of Alzheimer's disease are not uniform, varying from excitement at the
      possibility of significantly improving the personal and social burden of the
      disease to skeptical and nihilistic attitudes. Clinical practice from generous
      prescription to evidence-based guidelines and advising much stricter rules,
      mirror these attitudes. The epidemiological and clinical relevance of the issue
      requires understanding of the factors responsible for such discrepancies.
      Randomized clinical trials have only been able to address a few of the many
      variables that can affect the response to acetylcholinesterase inhibitors. The
      effect on behavioral symptoms, severe Alzheimer's dementia, and non-Alzheimer's
      forms of degenerative dementia need to be clarified as well as the modulating
      effect of frequently associated conditions such as cognitive changes due to
      physical diseases and cerebrovascular disease. The gap between evidence and
      clinical practice might be closed with appropriately designed observational
      studies rather than randomized clinical trials.

PMID- 11517996
TI  - Effectiveness of acupuncture for stroke: a systematic review.
AB  - BACKGROUND: Acupuncture has been suggested as a treatment for stroke
      rehabilitation, but the question whether it is effective has not been answered
      satisfactorily. PURPOSE: To summarise and critically review all randomised
      controlled trials of the effectiveness of acupuncture as a treatment for stroke.
      METHODS: Four independent computerised literature searches (in MEDLINE, Cochrane
      Controlled Trials Register, Embase, and CISCOM data bases) were conducted in June
      1999. All randomised-controlled trials that compared any form of needle insertion
      acupuncture to any form of non-acupuncture control intervention in the treatment
      of human stroke patients were included. Data were extracted independently by two
      authors and arbitrated by a third. The methodological quality of the included
      studies was assessed using the Jadad score. RESULTS: Nine randomised controlled
      trials with a total sample size of 538 patients were included. Two studies were
      assessor blind, one was subject blind, and one was assessor and subject blind.
      Two studies exclusively used manual acupuncture, five only electroacupuncture,
      and two used both. Outcome measures used were Scandinavian Stroke Scale, Chinese
      Stroke Scale or Recovery Scale, Barthel index, Nottingham Health Profile, Motor
      function, balance, and days in hospital. Of the nine studies, six yielded a
      positive result suggesting that acupuncture is effective, and three produced a
      negative finding implying that acupuncture is not superior to control treatment.
      Only two studies obtained a Jadad score of more than 3. These methodologically
      best trials showed no significant effect of acupuncture. CONCLUSION: Based on the
      evidence of rigorous randomised controlled trials, there is no compelling
      evidence to show that acupuncture is effective in stroke rehabilitation. Further,
      better-designed studies are warranted.

PMID- 11517997
TI  - Perfusion and diffusion magnetic resonance imaging in human cerebral venous
      thrombosis.
AB  - BACKGROUND: Diagnosis of cerebral venous thrombosis (CVT) is usually achieved by
      digital subtraction angiography or magnetic resonance angiography, while
      structural brain tissue damage can be assessed by computed tomography or magnetic
      resonance imaging (MRI). Using perfusion and diffusion weighted imaging (PWI,
      DWI) we aimed in this study to identify pathophysiological patterns corresponding
      to only functional and hence reversible tissue involvement. METHODS: PWI, DWI,
      and conventional MRI were performed in six CVT patients acutely and after 16-26
      days when their clinical condition had improved. All patients were treated with
      partial thromboplastin time-effective intravenous heparin. After intravenous
      administration of a paramagnetic contrast agent, bolus track PWI allows pixel
      based determination of mean transit time (MTT) and cerebral blood volume (CBV).
      DWI was performed with two different b values (0, 1000 s/mm2) for calculation of
      apparent diffusion coefficient (ADC) maps. RESULTS: In five of six cases
      increased MTT values were observed initially, whereas the CBV was normal,
      indicating a reduction of cerebral blood flow. ADC values were normal. On follow
      up after clinical recovery MTT prolongations had resolved. Areas with prolonged
      MTT did not evolve into structural lesions. CONCLUSION: In patients with CVT,
      prolongations of MTT in the absence of changes in CBV and ADC seem to indicate
      reversible involvement of brain tissue, a situation corresponding to the
      ischaemic penumbra.

PMID- 11517998
TI  - The effect of botulinum toxin injections to the calf muscles on freezing of gait
      in parkinsonism: a pilot study.
AB  - BACKGROUND: Freezing of gait (FOG) is a common and very disabling parkinsonian
      symptom, which is poorly understood and responds unsatisfactorily to medical
      treatment. We recently reported a unique patient with Parkinson's disease (PD)
      who had significant alleviation of FOG shortly after she was injected with
      botulinum toxin type A (BTX-A) for foot dystonia (Giladi et al. 1997). OBJECTIVE:
      To assess the effect of BTX-A injections into the calf muscles of parkinsonian
      patients on FOG. METHOD: BTX-A was injected in an open fashion into the calf
      muscles of 10 parkinsonian patients (age 55-75 years) with FOG as a predominant
      symptom. Response of FOG was assessed subjectively by the patient from worsening
      (-1) to marked improvement (+3). One patient was injected in a single blind
      fashion with saline or BTX-A after he had an initial good response. RESULTS:
      Seven patients reported different rates of improvement of FOG severity in 15 out
      of 17 therapeutic sessions. Four patients (40%) reported marked improvement (+3)
      of FOG in 5 sessions. Two patients reported no effect in two sessions. The mean
      duration of improvement was 6 weeks (range 1-12 weeks) with definite
      deterioration afterwards. The patient who was injected in a single blind fashion
      did not respond to saline injections but improved significantly with BTX-A
      treatment. CONCLUSIONS: We observed a clear temporal relationship between BTX-A
      injections into the calf muscles of parkinsonian patients and improvement of FOG.
      A double blind placebo controlled prospective study is needed before any
      conclusions can be drawn about the role of BTX-A injection in FOG.

PMID- 11517999
TI  - Neurological complications of primary Sjogren's syndrome.
AB  - OBJECTIVE: To better delineate the spectrum of neurological complications of
      primary Sjogren's syndrome (PSS). METHODS: A detailed neurological investigation
      was prospectively performed in a group of 25 consecutive patients with PSS
      followed in an internal medicine department between June 1996 and December 1997
      (Internal Medicine group). In addition, eleven patients with neurological
      complications of PSS were identified in the Neurological Department of the same
      institution during the same period (Neurological group). RESULTS: In the Internal
      Medicine group, neurological complications were discovered in 10/25 (40%)
      patients. Peripheral nervous system involvement was present in 4/25 patients from
      the Internal Medicine group and in 10/11 patients from the Neurological group and
      consisted mainly of axonal sensorimotor/sensory polyneuropathy. A motor neuron
      syndrome was identified in two patients. CNS involvement occurred in 7/25
      patients from the Internal Medicine group and in 4/11 patients from the
      Neurological group. Three patients had spinal cord involvement. Cognitive
      dysfunction was the most frequent finding (5/25 in the Internal Medicine group,
      3/11 in the Neurological group) characterized either by subcortical or
      corticosubcortical dysfunction. Cognitive impairment was not attributed to mood
      disturbance and was not associated with specific laboratory or radiological
      abnormalities. CONCLUSION: Neurological complications of PSS are frequent since
      they were present in 40% (10/25) of patients in a consecutive series of patients
      from a department of Internal Medicine. Although PNS involvement predominates,
      complications of PSS affecting the brain or spinal cord are not rare, with
      subcortical dysfunction as the main finding.

PMID- 11518000
TI  - Disturbed benzodiazepine receptor function at the onset of temporal lobe epilepsy
      -lomanzenil-binding in de-novo TLE.
AB  - PURPOSE: Epileptogenic foci exhibit disturbed function at the level of the
      benzodiazepine receptor. The aim of our study was to investigate the incidence of
      focal reductions of temporal benzodiazepine receptor binding (BRB) as assessed by
      scintigraphy with 123I-iomazenil in patients with denovo temporal lobe epilepsy
      (TLE). METHODS: Forty adult patients (age: 34+/-12 years) with cryptogenic denovo
      TLE underwent scintigraphy with 123I-iomazenil. In all patients, symptomatic
      epilepsy was excluded by clinical investigation and MRI. The median duration of
      TLE was seven months, and the patients had a median of three documented seizures
      in their history of disease. BRB was quantified in four temporal regions covering
      the whole temporal lobe. Temporal asymmetry values (ASY) were compared with data
      determined in 13 age-matched controls yielding Z-scores for global and regional
      temporal BRB. RESULTS: A significant reduction of temporal BRB was found in 19 of
      the 40 patients (48 %), mainly in mesial temporal regions; temporal BRB
      asymmetries were also found in patients with a short history of seizures and low
      seizure frequency (< or = 1 year; n = 32, 13/32 (41 %)). Only in the entire
      cohort did the magnitude of temporal reduction of BRB correlate with the duration
      of TLE as well as with the number of previous partial seizures (r = 0.40 and r =
      0.36; p < 0.03, respectively). CONCLUSIONS: Foci of decreased BRB can already be
      detected at the onset of TLE; their magnitude is related to ongoing epileptic
      activity.

PMID- 11518001
TI  - The impact of the introduction of the 14-3-3 protein assay in the surveillance of
      sporadic Creutzfeldt-Jakob disease in Catalonia.
AB  - The 14-3-3 assay in the CSF has a high predictive value for the diagnosis of
      sporadic Creutzfeldt-Jakob disease (CJD). Our objective was to analyse the trends
      in mortality and incidence rates of CJD in Catalonia, an autonomous community of
      Spain, setting the cut off point the date when the 14-3-3 assay was incorporated
      to our CJD surveillance system. Only definite and probable cases according to the
      criteria adapted from Masters and colleagues were included for the analysis.
      Familial cases were excluded after genetic analysis of the PrP gen. We found a
      quasi threefold increase in the incidence and mortality rates for CJD after
      introduction of the 14-3-3 assay in our surveillance system in 1997 as compared
      with the period 1993-1996. Our findings suggest an improvement of case
      ascertainment in part due to the introduction of the 14-3-3 assay in the
      surveillance system.

PMID- 11518002
TI  - Neuropsychological dysfunction in systemic lupus erythematosus is not associated
      with changes in cerebral blood flow.
AB  - Cognitive dysfunction is found in a considerable proportion of patients with
      systemic lupus erythematosus (SLE). SPECT provides an estimate of regional
      cerebral blood flow (rCBF) which has been claimed to be sensitive to detect brain
      involvement in SLE. It is, however, uncertain if these perfusion defects are
      related to cognitive dysfunction. In the present study we investigated whether
      cerebral dysfunction assessed by neuropsychological measures was associated with
      changes in rCBE Fifty-two SLE patients were examined with a battery of
      neuropsychological tests and MRI of the brain. For each patient 99mTC-HMPAO-SPECT
      was performed with the visual cortex as reference, and a reduction in rCBF of >
      15% was considered abnormal. Regional CBF was performed with an automated
      computer program quantitatively estimating blood perfusion in 16 symmetrical
      sectors of the brain. Several sectors of the brain showed varying areas of
      reduced rCBF with the temporal lobes most frequently involved. There were
      generally no associations between cognitive level of functioning and reduced
      rCBF. MRI demonstrated cerebral infarcts in 9 (17%) patients. In general rCBF was
      reduced in all sectors of the brain in patients with infarcts, although
      statistical significant difference in rCBF between patients with and without
      infarcts was only seen in the parietal lobe. Several neuropsychological functions
      were influenced by the presence of cerebral infarcts. There was no significant
      association between immunological measures and SPECT findings or
      neuropsychological measures. Neuropsychological dysfunction in SLE was associated
      with the presence of cerebral infarcts detected by MRI, but not by changes in
      rCBF. SPECT seems to add little if any information to that obtained by clinical
      examination, neuropsychological testing, and MRI. Since anticoagulation may
      prevent cerebral infarcts, such prophylactic intervention may be of importance in
      preventing cognitive deterioration.

PMID- 11518003
TI  - Influence of chronic bilateral stimulation of the subthalamic nucleus on
      cognitive function in Parkinson's disease.
AB  - BACKGROUND: The clinical efficacy of chronic deep brain stimulation in the
      treatment of parkinsonian patients with severe levodopa-related motor adverse
      effects has been repeatedly shown. Bilateral subthalamic nucleus (STN)
      stimulation has been shown to present an advantage over pallidal stimulation as
      it induces a higher antiakinetic effect and has positive effects on all
      parkinsonian symptoms. The morbidity of such surgery is usually considered to be
      very low. However, few studies have extensively examined the effects of chronic
      STN stimulation on cognitive function. OBJECTIVE: The aim of the present study
      was to assess the effects of chronic bilateral STN stimulation on performance in
      an extensive battery of neuropsychological tests, three months and one year after
      surgery. METHODS: Nine patients with Parkinson's disease were selected for STN
      electrodes implantation. They underwent a neuropsychological evaluation at one
      month before and at three months after surgery. Six of them were examined again
      at one year after surgery. RESULTS: Before surgery, no patient showed cognitive
      decline. At three months after surgery, no modification was observed for most
      tasks. The information processing speed tended to improve. There was a
      significant reduction of the performance in a delayed free recall test and a
      trend toward a significant reduction of categorial word fluency. At one year
      after surgery, most task measures did not change. Slight impairment was observed
      for tasks evaluating executive function. Examination of individual results showed
      that some patients (30% at 3 months after surgery) showed an overall cognitive
      decline. Behavioural changes were also observed in 4 patients with overall
      cognitive decline in one of them. CONCLUSION: In general, STN deep brain
      stimulation can be considered as a significant contribution to the treatment of
      severe Parkinson's disease However, in some patients it can induce overall
      cognitive decline or behavioural changes.

PMID- 11518004
TI  - The course of the terminal phase in patients with amyotrophic lateral sclerosis.
AB  - The fear of "choking to death" is on the mind of most patients suffering from
      amyotrophic lateral sclerosis (ALS). So far, however, there have been no
      systematic surveys concerning the dying phase in a general ALS population. We
      therefore performed a structured telephone interview with the relatives of 121
      patients who died from ALS and were followed by the Motor Neuron Outpatient
      Clinic of the Department of Neurology, University of Munich, Germany. These data
      are compared with those obtained by a retrospective analysis of medical records
      of 50 ALS patients who were followed by the Wisdom Hospice, Rochester, UK. The
      data show that most ALS patients (Germany 88%, UK 98%) died peacefully, and no
      patient "choked to death". The symptoms most frequently reported for the last 24
      hours were dyspnoea, coughing, anxiety and restlessness. Around half (G 55%, UK
      52%) of the patients died at home. The main palliative measures in place during
      the terminal phase were: home mechanical ventilation (G 21%, UK 0%), percutaneous
      endoscopic gastrostomy (G 27%, UK 14%), morphine (G 27%, UK 82%) and
      benzodiazepines (G 32%, UK 64%). The use of these palliative measures was judged
      to be beneficial by almost all relatives. These data support the hypothesis of a
      peaceful death process in ALS and should be communicated to patients and their
      relatives, at the latest after the onset of dyspnoea, to relieve unwarranted
      fears.

PMID- 11518005
TI  - No evidence of CNS infection with Chlamydia pneumoniae in patients with multiple
      sclerosis.

PMID- 11518006
TI  - Amnestic syndrome after lung transplantation by human herpes virus-6
      encephalitis.

PMID- 11518007
TI  - Rapidly progressing peripheral neuropathy with lactic acidosis and coproporphyria
      in a patient with HTLV-I associated T-cell leukaemia treated with zidovudine.

PMID- 11518008
TI  - Sural nerve abnormalities in sacral perineural (Tarlov) cysts.

PMID- 11518009
TI  - Immunosuppressive treatments in MS--side effects from azathioprine.

PMID- 11518010
TI  - Low cardiac 123I-MIBG uptake in late-onset familial amyloid polyneuropathy type I
      (TTR Met30).

PMID- 11518011
TI  - Tectal plate glioma presenting as generalised myasthenia in an adult.

PMID- 11518012
TI  - Successful treatment of excessive daytime sleepiness in Parkinson's disease with
      modafinil.

PMID- 11518013
TI  - Charles Edward Beevor (1854-1908).

PMID- 11518014
TI  - Mitral cell activity patterns optimise to reflect odour representation.

PMID- 11518015
TI  - Chitosan: some pharmaceutical and biological aspects--an update.
AB  - Chitosan, a natural polysaccharide, is being widely used as a pharmaceutical
      excipient. It is obtained by the partial deacetylation of chitin, the second most
      abundant natural polymer. Chitosan comprises a series of polymers varying in
      their degree of deacetylation, molecular weight, viscosity, pKa etc. The presence
      of a number of amino groups permit chitosan to chemically react with anionic
      systems, thereby resulting in alteration of physicochemical characteristics of
      such combinations. Chitosan has found wide applicability in conventional
      pharmaceutical devices as a potential formulation excipient, some of which
      include binding, disintegrating and tablet coating properties. The polymer has
      also been investigated as a potential adjuvant for swellable controlled drug
      delivery systems. Use of chitosan in novel drug delivery as mucoadhesive, gene
      and peptide drug administration via the oral route as well as its absorption
      enhancing effects have been explored by a number of researchers. Chitosan
      exhibits myriad biological actions, namely hypocholesterolemic, antimicrobial and
      wound healing properties. Low toxicity coupled with wide applicability makes it a
      promising candidate not only for the purpose of drug delivery for a host of drug
      moieties (antiinflammatories, peptides etc.) but also as a biologically active
      agent. It is the endeavour of the present review to provide an insight into the
      biological and pharmaceutical profile of chitosan. Various investigations carried
      out recently are reported, although references to research performed on chitosan
      prior to the recent reviews have also been included, where appropriate.

PMID- 11518016
TI  - Skin delivery of 5-fluorouracil from ultradeformable and standard liposomes in
      vitro.
AB  - The potential use of ultradeformable and standard liposomes as skin drug delivery
      systems was investigated in-vitro. An improved experimental design gave a good
      measure for skin deposition of drug. This avoided the contamination that can
      occur due to incomplete washing of the donor before direct determination of the
      amount of drug in the skin. The design used aqueous ethanolic receptor which is
      believed to diffuse into skin, disrupting deposited liposomes (if any) and thus
      releasing both bound and free drug. The receptor fluid was refined by testing
      different concentrations of ethanol. The applied dose was also optimized. Using
      the improved design and the optimum dose, an ultradeformable formulation was
      compared with four traditional liposomes for skin delivery of 5-fluorouracil (5
      FU). The best receptor was 50% aqueous ethanol and the optimum dose was 20
      microL. The ultradeformable formulation was superior to standard liposomes in the
      skin delivery of 5-FU. Of the traditional liposomes, the non-rigid preparation
      was the best. However, stabilization of the liposome membrane with cholesterol
      abolished the benefit of this non-rigid preparation. It was concluded that
      ultradeformable vesicles are promising agents for skin delivery of drugs.

PMID- 11518017
TI  - Application of Eudragit P-4135F for the delivery of ellagic acid to the rat lower
      small intestine.
AB  - Based on the assumption that the delivery of ellagic acid to its site of action
      would show an antiinflammatory activity in inflammatory bowel disease (IBD), we
      have prepared microspheres using a new pH-sensitive polymer, Eudragit P-4135F (P
      4135F), to deliver ellagic acid to the lower small intestine in rats. The
      microspheres were spherical in shape and the mean diameters were approximately
      100-150 microm. The amount of ellagic acid released from the microspheres
      decreased by increasing the formulated amount of P-4135F. The release
      characteristics of ellagic acid were pH-dependent. By considering the factors
      loading efficiency and microsphere particle size distribution, ellagic acid-2
      microspheres (P-4135F/ellagic acid = 1.65) were selected for further
      investigation. In a dissolution study, more than 95% ellagic acid was released
      within 0.5 h in pH 7.4 and 8.0 buffers. The release percent of ellagic acid was
      less than 40% in pH 6.8 and 7.0 and was less than 10% in pH 5.6 and 5.9. To
      observe the dissolution sites of the microspheres in the rat small intestine
      fluorescein was formulated in the microspheres as a tracer drug along with
      ellagic acid (50 mg kg(-1)). After intraduodenal administration of fluorescein
      labelled microspheres to rats, the plasma fluorescein level started to increase
      at 0.5 h, by which time the microspheres had reached the middle part of the
      ileum. Microspheres started to dissolve within 1.0 h and the peak plasma
      fluorescein concentration was observed at 3.0 h, when the majority of the
      administered microspheres were dissolved in the terminal ileum. These results
      suggested that P-4135F microspheres could deliver ellagic acid to the lower part
      of the small intestine, and that the released ellagic acid would be distributed
      into the caecum and the ascending colon.

PMID- 11518018
TI  - A simple, predictive, structure-based skin permeability model.
AB  - By an extension of our simple, molecular size-based model recently developed to
      describe octanol-water partition coefficients, we were able to obtain an entirely
      structure-based model that seems well suited to describe human skin permeability
      data. The corresponding equations not only eliminate the physicochemical
      interrelatedness of the parameters of the original Potts & Guy approach that was
      obtained from similar considerations, but also maintain its elegant simplicity
      and are consistent with a basic physicochemical model of the related phenomena.
      As the new model is structure based and fully computerized, it allows direct
      estimation of skin permeability for any molecule of known structure without the
      need to obtain octanol-water partition coefficients or other experimental data.

PMID- 11518019
TI  - Prevention of structural perturbations and aggregation upon encapsulation of
      bovine serum albumin into poly(lactide-co-glycolide) micropheres using the solid
      in-oil-in water technique.
AB  - Bovine serum albumin (BSA) was encapsulated into poly(lactide-co-glycolide) (PLG)
      microspheres by a solid-in-oil-in-water (s/o/w) technique. We tested whether
      perturbations in BSA secondary structure could be minimized during encapsulation
      by using trehalose and how this would influence BSA aggregation and release. BSA
      secondary structure was monitored noninvasively by Fourier-transform infrared
      spectroscopy. When BSA was co-lyophilized with trehalose, lyophilization-induced
      structural perturbations were significantly reduced. The formulation obtained
      (BSA-Tre) was encapsulated into PLG microspheres and, by optimizing critical
      encapsulation parameters, a loading efficiency of 85% was achieved. However, due
      to the loss of the excipient in the o/w emulsion step, the structure of BSA-Tre
      was more perturbed than before encapsulation. Excipient-loss and encapsulation
      induced structural perturbations could be prevented by saturating the aqueous
      phase in the o/w step with trehalose and by using the organic solvent chloroform.
      This in turn reduced the formation of soluble BSA aggregates. BSA was released
      from PLG microspheres using the improved formulations with an initial release in
      24 h of not more than 22%, followed by a sustained release over at least 2 weeks.
      In summary, optimization of the encapsulation conditions in the s/o/w procedure
      resulted in the encapsulation of BSA without procedure-induced structural
      perturbations and minimized the release of aggregated protein. This demonstrates
      that the s/o/w technique is an excellent alternative to the most common
      encapsulation procedure, namely the water-in-oil-in-water technique.

PMID- 11518020
TI  - Solid state properties of pure UC-781 and solid dispersions with
      polyvinylpyrrolidone (PVP K30).
AB  - The purpose of this study was to elucidate the physical structure of solid
      dispersions of the antiviral agent UC-781 (N-[4-chloro-3-(3-methyl-2
      butenyloxy)phenyl]-2-methyl-3-furancarbothioamide) with polyvinylpyrrolidone (PVP
      K30). Solid dispersions were prepared by coevaporating UC-781 with PVP K30 from
      dichloromethane. The physicochemical properties of the dispersions were evaluated
      in comparison with the physical mixtures by differential scanning calorimetry
      (DSC), X-ray powder diffraction, and FT-IR spectroscopy. We investigated the
      single crystal structure of pure UC-781. The data from single crystal analysis
      showed that UC-781 crystallized with orthorhombic symmetry in the space group
      Pcab. Its cell parameters were found to be; a = 8.1556(7) A,b = 17.658(2) A and c
      = 23.609(2) A; the unit cell was made up of eight molecules of UC-781. The
      molecules formed intermolecular hydrogen bonds between NH and thio groups, and
      were packed in a herringbone-like structure. The data from X-ray powder
      diffraction showed that crystalline UC-781 was changed into the amorphous state
      by co-evaporating it with PVP K30. From differential scanning calorimetry
      analysis, UC-781 peaks were observed in the DSC curves of all physical mixtures,
      while no peaks corresponding to the drug could be observed in the solid
      dispersions with the same drug composition up to the concentration of 50% w/w.
      The data from FT-IR spectroscopy showed the distortions and disappearance of some
      bands from the drug, while other bands were too broad or significantly less
      intense compared with the physical mixtures of the crystalline drug in PVP K30.
      Furthermore, the results from IR spectroscopy demonstrated that UC-781 interacted
      with PVP K30 in solid dispersions through intermolecular H-bonding.

PMID- 11518021
TI  - Synthesis of N-substituted 4,6-dioxo-imidazo[3,4-c] thiazoles and their analgesic
      activity in mice.
AB  - A new series of N-substituted dioxo-imidazo[3,4-c]thiazoles have been prepared
      and evaluated for their analgesic activity. The structures of these new
      derivatives were confirmed by lR, 1H NMR and 13C NMR spectra, and by elemental
      analysis. When administered intraperitoneally to mice all derivatives were devoid
      of any toxic effect, even at the high dose of 800 mg kg(-1). In the
      phenylbenzoquinone-induced abdominal constriction test in mice, eight of the nine
      synthesized compounds exhibited significant antinociceptive properties with ED50
      values (50% effective dose) ranging from 46.7 to 104.7 mg kg(-1)
      intraperitoneally. Further investigation demonstrated that analgesic activity of
      the most effective derivatives 5e and 5f partly involved opioidergic and/or
      noradrenergic pathways.

PMID- 11518022
TI  - Interaction of psychotropic drugs with monoamine oxidase in rat brain.
AB  - Literature observations indicate that some psychotropic drugs may have inhibitory
      activity towards monoamine oxidase (MAO). This study was undertaken to assess the
      potency, isozyme selectivity and mechanism of inhibition of representative first-
      and second-generation antidepressant drugs towards rat brain MAO-A and MAO-B.
      Five tricyclic antidepressants (imipramine, trimipramine, clomipramine,
      amitriptyline and doxepine) and three selective serotonin reuptake inhibitors
      (fluoxetine, fluvoxamine and citalopram) were examined. They showed inhibitory
      activity towards MAO-A and MAO-B, with clear selectivity for MAO-B (Ki in the
      micromolar range). Their mechanism of inhibition was competitive towards MAO-B
      and of a mixed competitive type towards MAO-A. The results suggest that some of
      the drugs examined might also contribute an MAO inhibitory effect in chronically
      treated patients.

PMID- 11518023
TI  - Transport studies of insulin across rat jejunum in the presence of chicken and
      duck ovomucoids.
AB  - Our aim was to evaluate the transport of insulin across rat jejunum in the
      presence of ovomucoids and to assess the effect of ovomucoids on intestinal
      tissue by studying the permeation of a lipophilic and a hydrophilic marker. Rat
      jejunal segments were mounted in a side-by-side diffusion chamber filled with
      Krebs bicarbonate buffer, bubbled with 95% O2/5% CO2 at a fixed flow rate and
      maintained at 37 degrees C. The permeation of insulin, a lipophilic marker ([7-
      3H] testosterone) and a hydrophilic marker (D-[1- 14C] mannitol) was evaluated in
      the presence of 0.5-1.5 microM duck ovomucoid (DkOVM) or chicken ovomucoid
      (CkOVM). For stability and permeation of insulin in the presence of alpha
      chymotrypsin, an enzyme-to-inhibitor ratio of 1:1 and 1:2 was used. In the
      absence of alpha-chymotrypsin, the permeability coefficient (Papp) of insulin at
      pH 7.4 was 0.922+/- 0.168 x 10(-7) cm s(-1), which decreased with increasing
      concentrations of DkOVM or CkOVM. Conversely, the permeation of the hydrophilic
      and lipophilic marker increased with increasing concentrations of CkOVM and
      DkOVM. In stability studies, the percentage of drug remaining was found to be 2
      fold higher at the 1:2 ratio than with the 1:1 ratio of enzyme to inhibitor. This
      was in agreement with the 2-fold increase in flux values of insulin in the
      presence of alpha-chymotrypsin and DkOVM at the 1:2 ratio of enzyme to inhibitor.
      The decrease in permeation of insulin in ovomucoids was unexpected. Marker
      transport studies indicated that ovomucoids have the potential to modulate
      transcellular and paracellular permeability. The flux enhancement of insulin in
      the presence of alpha-chymotrypsin and DkOVM is encouraging. The use of
      ovomucoids offers potential to enhance oral delivery of insulin and warrants
      further investigation.

PMID- 11518024
TI  - Antihyperglycaemic effect of Diamed, a herbal formulation, in experimental
      diabetes in rats.
AB  - Diamed is a herbal formulation composed of the aqueous extracts of three
      medicinal plants (Azardirachta indica, Cassia auriculata and Momordica
      charantia). We have investigated Diamed for its possible antihyperglycaemic
      action in rats with alloxan-induced experimental diabetes. Oral administration of
      Diamed (1.39 (0.25 g), 1.67 (0.30 g) or 1.94 (0.35 g) mL kg(-1)) for 30 days
      resulted in a significant reduction in blood glucose, glycosylated haemoglobin,
      and an increase in plasma insulin and total haemoglobin. The effect was highly
      significant after administration of the 1.94 mL (0.35 g) g(-1) body weight dose.
      Diamed also prevented a decrease in body weight. An oral glucose tolerance test
      was performed in experimental diabetic rats in which there was a significant
      improvement in glucose tolerance in the animals treated with Diamed. The effect
      was compared with 600 microg kg(-1) glibenclamide. The results showed that Diamed
      had antihyperglycaemic action in experimental diabetes in rats.

PMID- 11518025
TI  - Discrimination between the functional and biochemical effects of two herbal
      oxytocics on the rat myometrium.
AB  - This study on the rat myometrium is the first report where the effects of herbal
      extracts used as oxytocics in traditional medicine have been systematically
      analysed in the same preparation at the level of functional (contractile) and
      biochemical (second messenger generation) responses. Extracts of Agapanthus
      africanus and Clivia miniata (used in South African traditional medicine) were
      compared with other uterotonic agents with regard to their ability to stimulate
      phosphoinositide metabolism in the rat myometrium and cause accumulation of
      [3H]inositol phosphates. The maximal contractile response of the isolated rat
      myometrium in response to stimulation by the herbal extracts and agonists was
      compared with the maximal contractile response to cumulative addition of
      acetylcholine. The rank order of intensity of stimulation of [3H]inositol
      phosphate generation was: oxytocin > Agapanthus > prostaglandin
      F2alpha(PGF2alpha) > serotonin > acetylcholine > Clivia > ergometrine. This
      differed from the rank order of maximum contractile response: oxytocin >
      acetylcholine > PGF2alpha > serotonin approximately Clivia > Agapanthus >
      ergometrine. Activity was also identified in chemical fractions of the plants and
      components common to both plants have been identified in the isolated active
      fractions. These results have identified that the uterotonic activity of
      Agapanthus is linked to increased turnover of phosphoinositides as a signal
      transduction mechanism, whereas this appears to play a less significant role in
      the uterotonic activity of Clivia. This study illustrates the benefits of using
      the measurement of stimulation of phosphoinositide metabolism as a bioassay in
      phytomedical research.

PMID- 11518026
TI  - Inhibition of NF-kappaB-mediated gene transcription by the human A2B adenosine
      receptor in Chinese hamster ovary cells.
AB  - NF-kappaB is a transcription factor that plays a vital role in regulating
      inducible gene expression in immune and inflammatory responses. In view of the
      well documented effects of adenosine on immune and inflammatory responses, we
      have explored whether adenosine A1, A2B and A3 receptors regulate NF-kappaB
      activity in transfected Chinese hamster ovary (CHO) cells using a luciferase
      reporter gene construct. No increases in NF-kappaB activity were observed in CHO
      A1, -A2B and -A3 cells stimulated with the non-selective adenosine receptor
      agonist 5'-N-ethylcarboxamidoadenosine. Elevating intracellular cyclic AMP (cAMP)
      levels using forskolin (direct activator of adenylyl cyclase) and rolipram (type
      IV, cAMP-specific phosphodiesterase inhibitor), inhibited NF-kappaB activity in
      CHO cells. Adenosine A2B receptor stimulation also inhibited NF-kappaB activity,
      whereas adenosine A1 and A3 receptor activation had no effect. These data reflect
      the known coupling of adenosine A2B receptors to increases in cAMP. In
      conclusion, adenosine A1, A2B and A3 receptors do not directly activate NF-kappaB
      in CHO cells. However, adenosine A2B receptor activation significantly inhibited
      NF-kappaB activity. Inhibition of NF-kappaB activity by the adenosine A2B
      receptor may contribute to the anti-inflammatory effects of adenosine.

PMID- 11518027
TI  - Sustained ocular delivery of tilisolol to rabbits after topical administration or
      intravitreal injection of lipophilic prodrug incorporated in liposomes.
AB  - To improve the retention time of tilisolol in the precorneal area or vitreous
      body, we prepared liposomes incorporating the O-palmitoyl prodrug of tilisolol. O
      Palmitoyl tilisolol was completely incorporated in the liposomes. After topical
      administration of O-palmitoyl tilisolol liposomes to the rabbit eye, O-palmitoyl
      tilisolol rapidly disappeared from the tear fluid. The inclusion of 2% carmellose
      sodium slightly prolonged the retention of O-palmitoyl tilisolol in the tear
      fluid. After intravitreal injection of O-palmitoyl tilisolol liposomes, there was
      a relatively prolonged retention of O-palmitoyl tilisolol in the vitreous body.
      At 24 and 48 h after intravitreal injection of O-palmitoyl tilisolol liposomes,
      the tilisolol concentration in the vitreous body was significantly higher
      compared with the concentration after intravitreal injection of tilisolol
      liposomes.

PMID- 11518028
TI  - Effects of furocoumarins from Cachrys trifida on some macrophage functions.
AB  - Phytochemical and biological studies aimed at the discovery and development of
      novel antiinflammatory agents from natural sources have been conducted in our
      laboratory for a number of years. In this communication, three naturally
      occurring furocoumarins (imperatorin, isoimperatorin and prantschimgin) were
      evaluated as potential inhibitors of some macrophage functions involved in the
      inflammatory process. These furocoumarins have been tested in two experimental
      systems: ionophore-stimulated mouse peritoneal macrophages serve as a source of
      cyclooxygenase-1 and 5-lipoxygenase, and mouse peritoneal macrophages stimulated
      with E. coli lipopolysaccharide are the means of testing for anti-cyclooxygenase
      2 and nitric-oxidesynthase activity. All above-mentioned furocoumarins showed
      significant effect on 5-lipoxygenase (leukotriene C4) with IC50 values of < 15
      microM. Imperatorin and isoimperatorin exhibited strong-to-medium inhibition on
      cyclooxygenase-1- and cyclooxygenase-2-catalysed prostaglandin E2 release, with
      inhibition percentages similar to those of the reference drugs, indometacin and
      nimesulide, respectively. Of the three furocoumarins, only imperatorin caused a
      significant reduction of nitric oxide generation. Imperatorin and isoimperatorin
      can be classified as dual inhibitors, since it was evident that both
      cyclooxygenase and lipoxygenase pathways of arachidonate metabolism were
      inhibited by these compounds. However, selective inhibition of the 5-lipoxygenase
      pathway is suggested to be the primary target of action of prantschimgin.

PMID- 11518029
TI  - World Health Day 2001: minding the world's mental health.

PMID- 11518030
TI  - Public-health psychiatry in today's Europe: scope and limitations.
AB  - BACKGROUND: Public-health psychiatry is concerned, on the one hand, to ensure
      access to mental health services for all persons in need and, on the other hand,
      to advance knowledge of the social and environmental risk factors of mental
      disorders, and to establish a basis for preventive action. It is unclear how far
      current European Community (EC) policies will serve to achieve these objectives.
      This study aimed to review the mental health reform policies adopted in European
      countries since 1970, and to identify the main factors impeding progress in
      practice and research. METHOD: The relevant publications and statistical
      documentation for EC countries over the period in question were analysed.
      RESULTS: Despite a broad consensus on principles and aims, the implementation of
      mental health reforms in EC countries has been slow. Progress is subject to
      constraints imposed by service infrastructures, reductions in state
      responsibility, changing public attitudes, and growth of relative poverty. Much
      inferential evidence has accumulated on the importance of social risk factors
      such as unemployment and socio-economic deprivation, but most studies have had to
      rely on analysis of ecological correlations, based on administrative data, and
      there is an urgent need for more direct research making use of case- control and
      cohort study designs. CONCLUSIONS: EC harmonization will lead to improved mental
      health care only if the basic principles of public-health psychiatry are adopted
      and put into practice.

PMID- 11518031
TI  - Parent, child, and social correlates of parental discipline style: a
      retrospective, multi-informant investigation with female twins.
AB  - BACKGROUND: The type of parental discipline used in families appears to be
      related to parental characteristics, child temperament, and aspects of the social
      context. Within these three areas, we examine specific correlates of parental
      discipline (namely, limit setting and physical discipline) using a multiple
      informant model. METHOD: Using interview data from 2003 female twins from a
      population-based twin registry and 1472 of their parents, we examined
      retrospective reports of parental discipline from three perspectives. First,
      father and mother reporting separately on the type of discipline they provided
      for their offspring; second, each twin reporting on the type of discipline they
      received from their parents; and third, each parent reporting on the discipline
      provided by their spouse. Using a mixed model regression, we examined the impact
      on parental discipline of 25 potential predictor variables, as reported by
      parents, from three domains: social context, parental factors, and childhood
      vulnerability factors. RESULTS: There was a great deal of overlap between the
      independent variables for the two types of discipline in the areas of child
      vulnerability factors and family relationships, with similar effect sizes for
      child disobedience, teenage rebelliousness, and family discord. However, the
      profiles of parental characteristics associated with each type of discipline were
      quite different. Greater use of physical discipline was associated with less
      parental warmth, a higher incidence of parental lifetime generalised anxiety
      disorder, and more frequent religious attendance. Greater use of limit setting
      was associated with more years of parental education, younger age, and greater
      parental extroversion and authoritarianism. CONCLUSIONS: Parental
      characteristics, child temperament, and social context may all contribute to the
      frequency of discipline used in families, but parental characteristics may be
      most influential in determining the type of discipline used.

PMID- 11518032
TI  - Bias influencing maternal reports of child behaviour and emotional state.
AB  - BACKGROUND: Previous research has indicated that there may be only a modest
      degree of agreement between different reporters of a child's behaviour (mental
      health). This raises the possibility that some descriptions of the child's
      behaviour may reflect the personal characteristics of the respondent. We examine
      two potential sources of bias that may influence reports of a child's
      behaviour/mental health. The first is the mental or emotional impairment of the
      respondent; the second concerns gender-related expectations of children. METHODS:
      Mothers (and their children after the birth) were assessed at first clinic visit,
      3-5 days after the birth, then 6 months, 5 years and 14 years after the birth.
      Some 70% of respondents giving birth remained in the study at the 14-year follow
      up, leaving some 5277 cases for this analysis. At the 14-year follow-up, child
      behaviour (mental health) was assessed using the Child Behaviour Check List and
      the Youth Self Report. Maternal mental health was determined using the anxiety
      and depression subscales of the Delusions-Symptoms-States Inventory. RESULTS:
      Mothers who were not emotionally impaired reported fewer child behaviour problems
      than did the children themselves. As the mother's current emotional impairment
      increased, so her reports of the child's behaviour problems increased, when
      compared with the child's own reports. Further, mothers attributed more
      internalising symptoms to female respondents, and more externalising symptoms to
      male respondents, than did the child respondents themselves. CONCLUSIONS: Mothers
      differ systematically from their children when they are reporting their child's
      behaviour (mental health). The more emotionally impaired the mother, the greater
      the degree to which she imputes the child to have behaviour problems. Further,
      female children are attributed to have more internalising behaviours and male
      children externalising behaviours.

PMID- 11518033
TI  - Expressed emotion and the course of schizophrenia in Iran.
AB  - BACKGROUND: The influence of expressed emotion (EE) on the course of the
      schizophrenia has been studied in different countries. Cultural influence on the
      level of EE has shown the importance of examination of EE in different cultures.
      The present study examined the distribution of components of EE and influence of
      EE on the course of schizophrenia in Iran. METHODS: Two psychiatric centers from
      two dissimilar cities, Tehran and Hamedan, were chosen. Seventy-eight patients
      who suffered from schizophrenia based on the diagnostic criteria of DSM-III-R
      were selected. Interviews with 97 key family members were conducted using the
      Camberwell Family Interview. Psychiatrists who were blind to the EE status of the
      family household evaluated patients' symptoms based on a cohort study design
      during the 9-months follow-up. RESULTS: Sixty percent of the patients were living
      in a high EE household. The relapse rate in the high EE group was higher, but did
      not reach statistical significance. However, male patients as well as chronic
      patients were significantly more likely to relapse in the high EE group (P =
      0.05). CONCLUSIONS: The results suggested that high EE is a risk factor on the
      course of schizophrenia in Iran. The distribution of the components of EE showed
      differences compared to other cross-cultural studies. The results of this study
      can be used in planning appropriate psychoeducational programs for families of
      patients in Iran and culturally similar populations.

PMID- 11518034
TI  - The routine assessment of severity amongst people with mental illness.
AB  - BACKGROUND: Specialist mental health services are required to prioritise their
      work. To help this process numerous definitions of severe mental illness have
      been suggested. Such definitions vary, and are not necessarily valid or reliable.
      This investigation examined whether there was agreement over who constituted the
      most severely ill patients, amongst the case load of a community mental health
      team (CMHT). METHOD: Suggested guidelines for the prioritisation of patients were
      adapted after consultation and pilot reliability studies, and were then used by
      CMHT staff to rate their case loads (n=299). Test re-test, and inter-rater
      reliability studies were then conducted. A random sub-sample (n=120) was selected
      for further analysis to measure concurrent validity with respect to assessment of
      need, functioning and quality of life; and criterion validity. RESULTS: There was
      consistency in individual key worker decisions over time, and key worker ratings
      were valid in terms of disability, need and quality of life. Patients with a
      psychotic diagnosis were more likely to be rated as a high priority than those
      with a non-psychotic diagnosis. Agreement amongst different staff (inter-rater
      reliability) was poor, especially when ratings from CMHT staff were compared to
      external ratings. CONCLUSIONS: Our findings highlight the difficulties inherent
      in trying to agree on who constitute the severely mentally ill, and warn against
      the indiscriminate use of guidelines to determine access to services.

PMID- 11518035
TI  - Needs for mental health care and service provision in single homeless people.
AB  - BACKGROUND: Specific problems in sampling methodology, case-finding strategies
      and a standardised needs assessment in mentally ill homeless people have
      contributed to their being neglected as a mental health care clientele. METHOD:
      We assessed a representative sample of homeless people (n=102) in the highly
      industrialised city of Mannheim (Germany) regarding their prevalence of mental
      disorders (using the SCID) and their needs for mental health care (using the
      NCA). RESULTS: We found high prevalences, with 68.6% of all assessed homeless
      persons having a current mental disorder. Thus, needs for mental health care were
      very common, with unmet needs predominating in all problem areas, which was
      supported by a very weak service utilization. Thus, even in a region with a
      comprehensive community mental health care network, like the study area, mentally
      ill homeless people are widely under-provided. CONCLUSIONS: Results suggest that
      the traditional shelter system for homeless people carries most of the mental
      health care burden for their clientele and must be supported by adequate
      interventions from community-based mental health care services. A closer
      connection of both sectors and a better co-ordination of the care offers seems to
      be a prerequisite for helping to reduce unmet mental health care needs in this
      specific high-risk group.

PMID- 11518036
TI  - Infection of synoviocytes with HTLV-I induces telomerase activity.
AB  - To investigate the mechanism of synovial hyperplasia by human T-lymphotropic
      virus type I (HTLV-I) infection, the enzymatic activity of telomerase and
      expression of telomerase-related factors in HTLV-I infected synoviocytes were
      examined. Cultured synoviocytes obtained from four patients with osteoarthritis
      (OA) and four with traumatic joint disease (TJD) were infected by HTLV-I.
      Telomerase activity was detected by telomeric repeat amplification protocol
      (TRAP) assay. Expression of telomerase-related mRNAs such as telomerase reverse
      transcriptase (hTERT), telomerase RNA component (hTERC), and telomeric repeat
      binding factor 2 (TRF2) were also examined. Telomerase activity was detected in
      all HTLV-I-infected synoviocytes but not in uninfected synoviocytes. A remarkable
      induction of hTERT mRNA was observed in four of eight HTLV-I-infected
      synoviocytes, whereas expressions of hTERC, TRF2, and TEP-1 mRNAs were not
      changed. Our results clearly demonstrate that HTLV-I upregulates telomerase
      activity in synoviocytes probably via upregulation of hTERT activity. These
      findings suggest that telomerase activation in synoviocytes has an important role
      in upregulated proliferative activity of HAAP synoviocytes.

PMID- 11518037
TI  - Polymorphonuclear leukocyte adhesion to articular cartilage is inhibited by
      cartilage surface macromolecules.
AB  - The present studies deal with polymorphonuclear neutrophil (PMN) adhesion
      inhibitory properties of cartilage surface proteoglycans. Normal human PMN were
      used in adhesion experiments with bovine cartilage surfaces exposed to neutrophil
      elastase and reconstituted with fibronectin (Fn) or on plastic-bound Fn. An
      extract of cartilage surface small proteoglycans (SE) and purified fibromodulin
      (FM), decorin (DCN), biglycan (BGN), and aggrecan (AGN) on the surface of normal
      cartilage were used to test for inhibition of Fn-dependent cell adhesion. The PMN
      did not adhere to intact articular cartilage surfaces, whereas significant
      adhesion was measured using cartilage explants digested with elastase and
      reconstituted with Fn. Incubation of elastase-treated, Fn-reconstituted cartilage
      with 45 microg/ml SE inhibited PMN adhesion by 50.7 +/- 5.8% (P < 0.0001).
      Addition of 50 microg/ml purified FM to the reconstituted articular surfaces
      inhibited cell adhesion by 71.2 +/- 13.9% (P < 0.0001). Inhibition of PMN
      adhesion to plastic-bound Fn was seen with 1.7 microg/ml SE (20.4 +/- 8.0%).
      Maximal inhibition of 67.4 +/- 14.8% (P < 0.01) was obtained with 17.0 microg/ml
      SE. With FM, concentrations of 4.3 microg/ml resulted in 34.7 25.2 inhibition (P
      < 0.001), and maximal inhibition of 66.3 16.2% (P < 0.01) was obtained with 43.0
      microg/ml. Similar results were obtained with purified bovine DCN and BGN. The
      main component of cartilage matrix, AGN, failed to inhibit cell adhesion
      significantly. The results indicate that macromolecules normally present on
      articular cartilage surfaces act as a barrier to PMN adhesion. Since cartilage
      surface proteins are susceptible to breakdown by proteases from synovial fluid
      inflammatory cells, we postulate that the degradation of this barrier may be
      responsible for increasing PMN adhesion and subsequent cartilage damage in
      inflammatory arthritis.

PMID- 11518038
TI  - Increased levels of somatostatin in rat ankles with adjuvant arthritis.
AB  - Levels of somatostatin were investigated in the ankles and spinal cords of rats
      suffering from acute and chronic adjuvant arthritis. As measured by
      radioimmunoassay, somatostatin showed significantly higher concentrations only in
      chronic arthritic ankles. No significant difference was observed in somatostatin
      levels between the spinal cords of normal and arthritic groups. Using
      immunohistochemical labeling and electron microscopy, we observed increased
      somatostatin labeling in the mature bone matrix, monocytes, and polymorphonuclear
      cells of bone marrow and macrophage-like synovial cells of chronically arthritic
      rats. Understanding the mechanism(s) which lead to increased somatostatin in
      chronic arthritic joints may result in more effective treatment methods.

PMID- 11518039
TI  - Increased level of YKL-40 in sera from patients with early rheumatoid arthritis:
      a new marker for disease activity.
AB  - YKL-40 is a newly discovered major secretory protein of human chondrocytes and
      synoviocytes. We measured serum levels of YKL-40 in 52 patients with early onset
      rheumatoid arthritis (RA) by enzyme-linked immunosorbent assay (ELISA) during a 2
      year prospective follow-up, correlating values with laboratory and clinical
      variables and radiographic progression. Levels at baseline before antirheumatic
      therapy were significantly higher in patients than in healthy controls. The
      levels of YKL-40 correlated with laboratory and clinical markers of disease
      activity both at baseline and during follow-up. Baseline YKL-40 values correlated
      with baseline Larsen scores but did not predict radiographic progression.
      Baseline and mean YKL-40 values did not differ between fast and slow radiological
      progressions. Mean YKL-40 levels correlated with the number of swollen joints but
      were not predictors of radiographic progression. These results suggest that in
      early RA, serum YKL-40 is an inflammatory marker correlating with disease
      activity. However, its levels do not predict clinical course or radiographic
      progression.

PMID- 11518041
TI  - Clinical course and outcome of early rheumatoid arthritis.
AB  - We studied whether patients with seropositivity in early rheumatoid arthritis
      (RA) comprise a different clinical group than those with seronegativity. Four
      hundred seventeen patients with early RA according to the American College of
      Rheumatology criteria (disease duration less than 1 year) were retrospectively
      studied by analysis of demographic, clinical, laboratory, radiological, and
      therapeutic disease characteristics from the time of diagnosis until the end of
      the study period (1981 1999) using a data base. There were 248 seropositive
      patients and 169 seronegative patients with RA. No statistically significant
      differences were seen between the two groups before commencement of the study
      period in relation to age of disease onset, male:female ratio, and disease
      duration. However, seropositive patients showed longer medical follow-up. In
      addition, at disease onset, seropositive RA patients presented more frequently
      with symmetrical polyarthritis and small joint involvement than seronegative
      patients. The seropositive group also had more tender and swollen joints, weaker
      grip strength, and higher erythrocyte sedimentation and C-reactive protein rates
      during the follow-up period. In contrast, the seronegative group had less severe
      radiological findings and greater functional ability at the end of the study. In
      Greek patients with early RA, rheumatoid factor seems to be a predictor of more
      severe disease activity.

PMID- 11518040
TI  - Antineutrophil cytoplasmic antibodies in patients with systemic lupus
      erythematosus: prevalence, antigen specificity, and clinical associations.
AB  - Fifty-five patients with systemic lupus erythematosus (SLE) were examined for
      antineutrophil cytoplasmic antibodies (ANCA) by indirect immunofluorescence
      (IIF). Enzyme-linked immunosorbent assay (ELISA) for ANCA against myeloperoxidase
      (MPO), lactoferrin (LF), proteinase 3 (PR3), elastase (HLE), and
      bactericidal/permeability-increasing protein (BPI) was performed. The prevalence
      of ANCA by IIF was 29.1% (16/55 patients). MPO-ANCA were found in 10.9% (6/55),
      LF-ANCA in 18.2% (10/55), PR3-ANCA in 12.7% (7/55), BPI-ANCA in 23.6% (13/55),
      and HLE-ANCA in 1.8% (1/55). The levels of BPI-, LF-, and PR3-ANCA correlated
      with disease activity. A significant association between serositis and the
      presence of BPI-, LF-, and PR3-ANCA was observed, and PR3-ANCA were found to be
      associated with arthritis as well. Our results demonstrate that ANCA of various
      specificities occur in SLE, and BPI appears to be an important target antigen.

PMID- 11518042
TI  - Functional changes in patients with spondylarthropathy. A controlled trial of the
      effects of short-term rehabilitation and 3-year follow-up.
AB  - A cohort of 25 patients with spondylarthropathy (SpA) participated in a 3-year
      follow-up study of functional changes before and after an intensive 3-week
      inpatient course. They answered questions in the following functional
      status/disability indices: Bath ankylosing spondylitis functional index (BASFI),
      Dougados functional index (DFI), health assessment questionnaire for
      spondylarthropathy (HAQ-S), Bath ankylosing spondylitis disease activity index
      (BASDAI), Bath ankylosing spondylitis patient global assessment (BAS-G), and
      horizontal visual analogue scale for stiffness (stiffness VAS) before and after
      the course and 3 years later by mail. A control group of 18 consecutive SpA
      patients from the waiting list for an inpatient course filled in the same
      questionnaires as study patients 3 months before entry and again 3 weeks later at
      home without rehabilitation. During the waiting time for the inpatient course,
      control group global assessments (BASDAI, BAS-G, and stiffness-VAS) worsened
      slightly, and BASFI but not HAQ-S and DFI scores remained unchanged in the 3
      weeks without treatment. The results of the 25 study patients showed small and
      not significant improvements in all functional index scores (BASFI -0.5 points,
      DFI -1.1, and HAQ-S 0.17), whereas improvements were significant in BAS-DAI, BAS
      G, and stiffness-VAS (-13 mm, 13 mm, and -11 mm, respectively) after the 3-week
      inpatient course. At 3-year follow-up, these small changes had disappeared and
      the changes were not significant. The global indices and BASFI worsened slightly
      (0.4) from baseline results, while DFI was slightly better (-0.4) and HAQ-S
      remained at the post-treatment level after 3 years. Thus, BASFI was the most
      sensitive to changes, whereas DFI and HAQ-S were relatively insensitive. All six
      indices correlated highly significantly with each other (ICC 0.53-0.94). The
      natural course of spondylarthropathy leads to progression of functional
      impairments, which seems to be preventable with intensive rehabilitation, at
      least in the short term. Among the three functional indices, BASFI seems to be
      the most sensitive tool.

PMID- 11518043
TI  - Giant cell arteritis mimicking a testicular tumour.
AB  - Giant cell arteritis involving the testis was identified incidentally upon
      orchidectomy of a right testicular mass. The mass looked like a malignant process
      on ultrasound. The patient also had generalised disease and was treated
      appropriately. Giant cell arteritis involving the bladder, prostate, uterus, and
      adnexa have been described before. To our knowledge, this is the first described
      case of giant cell arteritis affecting the testis.

PMID- 11518044
TI  - Morphometric differences in pulmonary lesions in primary and secondary ARDS. A
      preliminary study in autopsies.
AB  - The present study was undertaken in order to describe the morphological
      differences between pulmonary lesions in acute respiratory distress syndrome
      originating from direct pulmonary injury (ARDSp) and those originating from
      extrapulmonary injury (ARDSexp). We investigated a total of 38 ARDS-patients (27
      males) ranging in age from 19 to 75 years, classified according to underlying
      disease in pulmonary (ARDSp) and extrapulmonary disease (ARDSexp). The extent of
      acute diffuse alveolar damage was assessed morphometrically on histologic gross
      sections in the upper and lower lobes of one lung. The lesions showed
      quantitative differences in extent and distribution according to underlying
      disease (primary pulmonary or secondary involvement). In pulmonary ARDS, a
      predominance of alveolar collapse (16.6%+/-12.3% versus 10.3%+/-11.9%, p = 0,03),
      fibrinous exudate (1.7%+/-3.2% versus 0.4%+/-1.1%, p = 0.01) and alveolar wall
      edema (11.2%+/-7.4% versus 6.6%+/-4.4%, p = 0,05) were found compared to
      extrapulmonary ARDS. We conclude that the morphology of acute diffuse alveolar
      damage (DAD) is mainly determined by underlying disease (pulmonary ARDS or
      extrapulmonary ARDS) differing in quantitative terms within the lung.
      Physiological, radiographic and respiratory system mechanics differences
      described in ARDSp and ARDSexp may therefore be due to morphometric differences
      in pulmonary lesions.

PMID- 11518045
TI  - Evaluation and reinforcement of the correlation of S-phase fraction with nodal
      metastases, tumor grade and tumor size in breast carcinoma patients in Pakistan.
AB  - The aim of this study was to evaluate the S-phase fraction (SPF) of tumors in
      breast cancer patients in Pakistan. Its association with the traditional
      morphological prognostic markers, i.e., axillary lymph node metastasis, tumor
      size and grade, was also studied. Flow cytometry was used to estimate SPF on
      breast cancer tissues from 166 patients reported at the Aga Khan University
      Hospital between the years 1997 and 2000. Univariate analysis was done to find
      any association between SPF and the aforesaid variables. For the ease of
      analysis, the cases were subdivided into two categories depending on the SPF
      value, i.e., <10% (low-risk group) and > or = 10% (high-risk group). The mean and
      median SPF values were 21.45% and 20.035%, respectively, with a range of 3.26% to
      54.30%. Twenty-six (15.66%) of the cases had SPF <10%, 57 (34.34%) had SPF from
      10%-20%, and 83 (50%) had SPF >20%. A significant correlation between SPF and
      nodal metastasis was observed (p = 0.0111), but not between SPF and the number of
      lymph nodes involved when metastatic cases were subdivided into <4 lymph node
      positive cases and > or =4 lymph node-positive cases. Significant correlations
      were also found between SPF and tumor grade (p = 0.0244), as well as between SPF
      and tumor size (p = 0.048). In conclusion, DNA flow cytometric analysis of SPF
      carried out in our laboratory could reasonably predict the chances of lymph node
      metastasis, tumor grade and size in breast cancer patients, thus proving to be an
      important prognostic marker in the Pakistani setting. This requires further
      investigations regarding the survival of patients so as to evaluate its capacity
      of predicting the outcome of Pakistani patients.

PMID- 11518046
TI  - Perineurial cell differentiation in neurofibromas. Report of eight cases
      including a case with composite perineurioma-neurofibroma features.
AB  - Among 99 cases of neurofibroma (NF), eight tumors (8%) contained epithelial
      membrane antigen (EMA)-positive perineurial cells inside the lesions. These cells
      were numerous and represented a significant part of the tumor cell population. In
      case 7, EMA-positive cells represented approximately half of the tumor. These
      patients' ages ranged from 23 to 73 years (average 51 years). Six patients were
      females and two were males. Neurofibromatosis type 1 was present in one case. The
      histological types of neurofibromas with EMA-positive cells were as follows:
      cutaneous, well-circumscribed, localized type in four cases; cutaneous diffuse
      type in one case; subcutaneous, well-circumscribed type in two cases; and
      subcutaneous plexiform type in one case. Perineurial cell differentiation was
      suspected by examining routinely stained sections in four cases; it was
      unsuspected in four cases. The perineurial cells were arranged in a pattern
      similar to that of "pure" perineurioma. They possessed thin bipolar processes and
      were arranged in laminar fascicles and whorls. In cellular areas, the cytoplasm
      was more eosinophilic and cell borders were poorly visible. In contrast, when the
      stroma was myxoid, it accentuated the shape of individual cells. As these
      morphological features of perineurial cell differentiation in NF are not entirely
      specific, EMA staining is recommended to prove the perineurial cell
      differentiation in neurofibromas. An additional immunohistochemical result of
      this study is the presence of numerous CD34-positive cells in all neurofibromas,
      which is similar to previous studies.

PMID- 11518047
TI  - Morphometric comparison of the quantity of the mesangial deposits in rebiopsied
      patients with idiopathic mesangial proliferative glomerulonephritis.
AB  - We examined 17 patients with idiopathic mesangial proliferative
      glomerulonephritis (MPG) who had undergone repeated renal biopsies and for whom
      both light and electron microscopy as well as immunofluorescence microscopy and
      full clinical data were available. Ultrastructural investigations were carried
      out by a computer image analysis system to compare quantitatively the area of the
      mesangial deposits in serially biopsied patients with MPG, and to find out
      whether this parameter would correlate with the degree of proteinuria. Another
      purpose of this study was to verify whether the intensity of the glomerular
      infiltrates of monocytes/macrophages depends on the accumulation of mesangial
      deposits. Comparisons between the first biopsy and rebiopsy showed that the mean
      values of the deposit area per mesangial area were significantly decreased at
      rebiopsy. Similarly, the glomerular infiltrates of monocytes/macrophages were
      significantly greater at the first biopsy than they were at rebiopsy. At the
      first biopsy and at rebiopsy, a significant, positive correlation existed between
      the density of the mesangial deposits and glomerular monocytes/macrophages as
      well as proteinuria. Glomerular infiltrates of monocytes/macrophages correlated
      positively with proteinuria in both the first biopsy and rebiopsy groups. In
      conclusion, this study points out that the density of the mesangial deposits and
      glomerular infiltrates of monocytes/macrophages were significantly decreased at
      rebiopsy, as compared with the first biopsy. Cited data and results of the
      correlative study correspond with the observation that in most of our serially
      biopsied patients, proteinuria at rebiopsy was significantly lower than that at
      the initial biopsy, a finding that might explain the clinical improvement in
      these cases.

PMID- 11518048
TI  - Immunohistochemical cathepsin-D expression in breast cancer: correlation with
      established pathological parameters and survival.
AB  - Breast cancer is an increasingly important cause of illness and death among
      women. In recent years, several novel prognostic determinants of breast cancer
      have been identified, including Cathepsin-D (CD) protein. CD protein expression
      was analyzed immunohistochemically (IHC) in tumor specimens (315 patients) of
      infiltrating ductal breast carcinoma. These patients also had axillary lymph node
      sampling. Overexpression of CD was observed in 39% of the tumors. IHC results
      were compared with the histological grade. Seventy nine percent (n = 95; 79%)
      tumor positivity was seen in grade II tumors, followed by grade I (n = 13; 11%)
      and grade III tumors (n = 12; 10%). Axillary lymph node metastasis had no
      significant correlation with CD positivity (p > 0.05). Bone metastases were
      significantly correlated with CD positivity (p < 0.05). CD positivity showed no
      significant correlation with disease-free and overall survival (p > 0.05). At a
      median follow-up of 48 (4 years) months in CD-positive patients, overall survival
      was 3.17 years, and disease-free survival 2.67 years. The overall survival of CD
      negative tumor patients was 3.50 years, and disease-free survival was 2.93 years.
      We conclude that in comparison with cytosol-based quantitative studies, CD
      expression is not a good prognostic marker when, as in all ICH studies, only the
      expression in the tumor is considered.

PMID- 11518049
TI  - Fetal cardiac rhabdomyomatosis as a prenatal marker for the detection of latent
      tuberous sclerosis. An autopsy case report.

PMID- 11518050
TI  - Distinction between lipoma and liposarcoma by MDM2 alterations: a case report of
      simultaneously occurring tumors and review of the literature.
AB  - We investigated a lipoma and a well-differentiated/dedifferentiated liposarcoma
      (WD/DDL), occurring simultaneously in one patient for the possible role of p53
      and mdm2 in the molecular oncogenesis of liposarcoma and tumor progression. The
      hypothesis tested was if there is a continuum in the development from lipoma to
      liposarcoma. Lipoma was characterized by a lack of p53 mutation, p53 LOH and p53
      protein expression, as well as by mdm2 amplification and mdm2 protein expression.
      p53 mutation and p53 LOH were found neither in the well-differentiated nor in the
      dedifferentiated parts of the liposarcoma. In contrast, mdm2 amplification and an
      increase in mdm2 protein expression were found to be associated with malignancy
      and dedifferentiation, whereas p53 protein expression was only slightly
      increased. These findings indicate that mdm2 constitutes one of the most common
      targets for molecular aberration in WD/DDL. We suggest that mdm2 is a marker
      distinguishing between ordinary lipoma and well-differentiated liposarcoma, and
      that the genesis of these tumors is different.

PMID- 11518051
TI  - Aggressive osteoblastoma of the mandible closely simulating calcifying epithelial
      odontogenic tumor. Report of two cases with unusual histopathologic findings.
AB  - Aggressive osteoblastoma is a rare bone-forming neoplasm composed of prominent
      epithelioid cells that demonstrate locally invasive growth with a high rate of
      recurrence but no metastatic potential. Clinical, radiographic and pathologic
      features of mandibular aggressive osteoblastoma in a 21-year-old African-American
      male and a 12-year-old Caucasian female are presented. Both tumors were resected
      with wide surgical margins and neither patient had adjuvant radiation or
      chemotherapy. The patients showed no evidence of local recurrence or distant
      spread either clinically or radiographically after two years of follow-up. These
      tumors were composed of solid sheets of pleomorphic epithelioid cells,
      eosinophilic amorphous osteoid with foci of calcification, which closely
      simulated amyloid. Differentiation of this tumor from histologically similar
      calcifying epithelial odontogenic tumor and low-grade osteosarcoma proved
      difficult. Immunohistochemical study with osteocalcin confirmed the osteoblastic
      nature of these epithelioid cells.

PMID- 11518052
TI  - Lymphoepithelioma-like carcinoma of rectum: possible relation with EBV.
AB  - Lymphoepithelioma-like carcinoma (LEC) of the colon is very rare. Here we report
      a case of LEC originating in the rectum that was closely associated with Epstein
      Barr virus (EBV) infection. The histologic and immunohistologic features, namely,
      poorly differentiated adenocarcinoma with lymphoid stroma, showed this tumor to
      be an LEC. The EBV genome was detected by PCR using DNA obtained from tumor
      tissue sections. Immunohistochemically, EBV-determined nuclear antigen 2 was
      detected in the tumor cells, and in situ hybridization using EBV-encoded small
      RNAs probe showed positive labeling in some tumor cells together with a few
      stromal lymphoid cells. There are some reports of LEC cases that originated in
      the colon; however, a relation with EBV was not demonstrated. We report here a
      case of LEC of the rectum demonstrating a possible relation with EBV.

PMID- 11518053
TI  - Molecular diagnosis of a Mycobacterium chelonae infection.

PMID- 11518054
TI  - A tribute to Prof. Dr. E. Mutschler. Biocenter Symposium on Drug Therapy:
      Advances in St. John's Wort Research. February 2000, Frankfurt, Germany.

PMID- 11518055
TI  - Biochemical mechanisms of action of Hypericum LI 160 in glial and neuronal cells:
      inhibition of neurotransmitter uptake and stimulation of extracellular signal
      regulated protein kinase.
AB  - We have investigated biochemical mechanisms that may underlie the antidepressant
      effects of Hypericum LI 160. We found that LI 160 inhibits uptake of serotonin
      and norepinephrine in cultures of rat cortical astrocytes. Observed differences
      in the kinetic parameters Km and Vmax as well as in the recovery of uptake after
      removal of Hypericum indicates that LI 160 does not affect serotonin and
      norepinephrine transport in the same manner. This suggests that multiple
      components of the extract can mediate inhibition of these neurotransmitter
      transporters. Hypericum LI 160 also inhibits serotonin uptake in neuronal
      cultures from serotonergic-rich raphe nuclei; concentration-response studies
      indicate LI 160 is 25 times more potent in terms of inhibition of serotonin
      uptake in neurons than in astrocytes. In addition, Hypericum LI 160 inhibits
      norepinephrine uptake in SK-N-SH cells, a human neuroblastoma cell line enriched
      in norepinephrine transporters. A chemical constituent of LI 160, hyperforin, is
      about 10 to 20 times more potent than LI 160 in inhibiting neurotransmitter
      uptake in astrocytes and neuronal cells; this finding is consistent with the
      observation that hyperforin comprises 5% of LI 160 extracts. As several weeks are
      needed to achieve a clinical response with antidepressants, we have also
      investigated whether Hypericum LI 160 affects biochemical mechanisms that
      underlie long-term changes such as gene expression. We found that LI 160
      stimulates a sustained activation of extracellular signal regulated protein
      kinase (ERK), a key component of a signal transduction pathway involved in gene
      expression. Taken together, our findings suggest that Hypericum LI 160 can affect
      rapidly-acting as well as slower-developing, long-term biochemical mechanisms
      related to depressive disorders.

PMID- 11518056
TI  - Effects of two different extracts of St. John's wort and some of their
      constituents on cytochrome P450 activities in rat liver microsomes.
AB  - We examined two commercially available St. John's wort extracts and some of their
      constituents for their potential in inducing rat cytochrome P450 (CYP450) enzyme
      activities after oral administration. None of the extracts or pure constituents
      tested enhanced the hepatic cytochrome content or the activity of cytochrome P450
      isozymes in rat liver microsomes. Our results demonstrated that the reported
      interactions between St. John's Wort and various other drugs are not mediated by
      CYP 450 isoforms present in rat liver.

PMID- 11518057
TI  - Stimulation of glutamate, aspartate and gamma-aminobutyric acid release from
      synaptosomes by hyperforin.
AB  - Hyperforin is one pharmacologically active constituent of the medicinal herb
      Hypericum perforatum. The mechanism of its antidepressant-like activity is
      currently considered to be the inhibition of synaptic reuptake of
      neurotransmitters. Here, we will demonstrate that it also stimulates the release
      of glutamate from rat cortical synaptosomes, and that this effect is preceded by
      an increase in their free calcium [Ca2+]i levels. These hyperforin-related
      effects were also observed in the absence of Ca2+ in the medium. Although we
      noted enhanced glutamate, aspartate and GABA release under the influence of
      hyperforin, the release of various other amino acids was not enhanced. In
      contrast, reserpine did not influence the release of any of the amino acids
      studied. Adding hyperforin to synaptosomal suspension decreased their pHi, which
      returned to basal levels under certain incubation conditions. It also prevented
      the generation of ATP-induced pH gradients of isolated synaptic vesicles, and
      preformed pH-gradients were reversed by it. We will discuss the implications of
      our studies in understanding the mechanisms of hyperforin activity in relation to
      current findings on its pharmacological activity profile. Our observations
      suggest that neurotransmitter release stimulation from synaptosomes and the
      previously reported reuptake inhibitory properties of hyperforin are consequences
      of its effects on synaptosomal ionic homeostasis, and that it is not a reserpine
      like agent.

PMID- 11518058
TI  - In vivo neurotransmitter release in the locus coeruleus--effects of hyperforin,
      inescapable shock and fear.
AB  - Hyperforin, the main antidepressant constituent of Hypericum perforatum,
      influences the extracellular concentrations of transmitters in vitro and in vivo.
      In vivo experiments have shown that hyperforin enhances the extracellular
      concentrations of dopamine, norepinephrine, serotonin and glutamate in the locus
      coeruleus. Hyperforin-free Hypericum extract also elevates the extracellular
      concentrations of dopamine and norepinephrine in the locus coeruleus, but, in
      contrast to hyperforin, the extracellular concentration of serotonin is
      diminished. The differing profiles of hyperforin and hyperforin-free Hypericum
      extract on the extracellular transmitter concentrations point to the presence of
      an additional biologically active compound in Hypericum perforatum. Inescapable
      shock increases the release of monoamines and several amino acids, as well as
      motility, blood pressure and heart rate. Conditioned fear, similar to hyperforin
      free Hypericum extract, decreases the release of serotonin in the locus
      coeruleus. Conditioned fear also leads to tachycardia. The latter finding shows
      that telemetric heart rate recording is a good index for conditioned fear. In
      vivo findings confirm the idea that the anti-depressive properties of Hypericum
      extract and hyperforin result from increases in extracellular neurotransmitter
      concentrations. Since hyperforin-free extract, like conditioned fear, reduces the
      extracellular concentration of serotonin, hyperforin may be more beneficial than
      Hypericum extract in the treatment of depressive disorders.

PMID- 11518059
TI  - A current review of the antimicrobial activity of Hypericum perforatum L.
AB  - A petrolether extract of the areal parts of Hypericum perforatum L. was reported
      to be active against gram-positive bacteria. Hyperforin, a phloroglucin
      derivative was shown to be the antimicrobial principle. Hyperforin exhibited an
      excellent effect against methicillin-resistant strains of Staphylococcus aureus
      with a MIC value of 1.0 microg/ml. A butanol fraction of St. John's Wort revealed
      anti-Helicobacter pylori activity with MIC values ranging between 15.6 and 31.2
      microg/ml. Recently, hydrous solutions of Hypericum perforatum teas were found to
      be antimicrobially effective against gram-positive bacteria with special activity
      towards methicillin-restistant strains of Staphylococcus aureus (MIC values: 1.3
      to 2.5 mg herb/ml).

PMID- 11518060
TI  - Acute and chronic actions of a dry methanolic extract of Hypericum perforatum and
      a hyperforin-rich extract on dopaminergic and serotonergic neurones in rat
      nucleus accumbens.
AB  - Dry hydroalcoholic extract of Hypericum perforatum L. is effective in the
      treatment of mild-to-moderate depression. Neither the mechanism of action nor the
      component or components of the extract responsible are known to date. In several
      in vitro and ex vivo models, the extract and hyperforin, one of its active
      components, cause changes similar to those of tricyclic antidepressants. Little
      is known about effects on a complex neuronal system relevant to antidepressant
      actions such as the mesolimbic system in the brain. In animal models of
      depression, the levels of dopamine were reduced in the nucleus accumbens, which
      is an important part of the mesolimbic system. These and other deficits were
      compensated by imipramine. We investigated the actions of the methanolic
      Hypericum extract LI 160 and a hyperforin-rich research extract in the shell
      region of the nucleus accumbens under in vivo conditions after acute
      administration, and after application repeated fourteen times. Both extracts
      induced an increase of dopamine (DA) and 5-hydroxytryptamine (5-HT) levels
      measured by in vivo microdialysis. The dose-response curve followed an inverse U
      shape. Repeated application caused a rapid tolerance of DA but not of 5-HT
      neurones. Similar changes were observed after acute and repeated applications of
      imipramine. Several lines of evidence have suggested other active components in
      the Hypericum extract. The potency of hyperforin surpassed that of imipramine in
      the acute release of both DA and 5-HT by the nucleus accumbens. The effect of
      hyperforin correlated well with the inhibiting potency on high-affinity DA and 5
      HT uptake. The missing effect of relatively high doses on DA and 5-HT levels as
      found in dose-response experiments may be explained by self-inhibition caused by
      the activation of autosomal receptors and by the inhibition by GABA. The
      inhibition of neuronal GABA transport occurs at somewhat higher concentrations of
      hyperforin. In conclusion, the findings demonstrate an imipramine-like effect of
      methanolic Hypericum extract LI 160 and of hyperforin on mesolimbic, dopaminergic
      and serotonergic neurones in acute and chronic experiments, which probably
      contributes to the antidepressant action of the medication. The methanolic
      Hypericum extract contains active compounds other than hyperforin.

PMID- 11518062
TI  - The effects of extracts from St. John's Wort and Kava Kava on brain
      neurotransmitter levels in the mouse.

PMID- 11518061
TI  - Neuroendocrine effects of Hypericum extract WS 5570 in 12 healthy male
      volunteers.
AB  - In the present study, the effects of acute p.o. administration of placebo at 300
      mg and 600 mg of WS 5570 Hypericum perforatum extract on cortisol (COR), growth
      hormone (GH) and prolactin (PRL) secretion were examined in twelve physically and
      mentally healthy subjects. WS 5570 is a hyperforin containing extract of St.
      John's Wort which has been proven effective in mild to moderate depression. After
      inserting an i.v. catheter, blood samples were drawn one hour prior to the
      administration of WS 5570 or placebo, at the time of application and up to five
      hours after application in 30-minute intervals. Plasma concentrations of COR, GH,
      and PRL were determined in each blood sample by double-antibody RIA methods. No
      PRL stimulation could be observed after placebo or after WS 5570 (300, 600 mg). A
      small but statistically significant elevation in GH AUC values occurred after 300
      mg of WS 5570. After 600 mg of WS 5570, a clear-cut COR stimulation was observed,
      occurring from 30 up to 90 minutes after the application. In this period of time
      (from t = 30 min to t = 90 min), the mean COR concentrations were significantly
      higher after 600 mg of WS 5570 compared to placebo. 300 mg of WS 5570 did not
      show any effects on COR secretion. We propose that the Hypericum extract WS 5570
      is able to influence central neurotransmitters, thereby causing COR stimulation
      in a dose-dependent manner.

PMID- 11518063
TI  - Neurochemical studies with St. John's wort in vitro.
AB  - The effect of extracts and constituents of St. John's wort, Hypericum perforatum,
      at various CNS receptors were studied by radioligand binding techniques in order
      to determine a profile of pharmacological activity in vitro. Binding inhibition
      was examined for the G-protein coupled opioid, serotonin (5-HT), histamine,
      neurokinin and corticotropin releasing factor (CRF) receptors, for the steroid
      estrogen-alpha receptor and for the ligand-gated ionchannel GABA(A) receptor.
      Hypericin showed the most potent binding inhibiton of all tested constituents to
      human CRF1 receptor with an IC50 value of 300 nM. Preliminary GTPgamma35S binding
      studies to CRF1 coupled G-protein indicated an antagonistic action for hypericin.
      The acylphloroglucinole hyperforin failed to inhibit 125I-astressin binding to
      hCRF, receptor up to 10 microM. Hyperforin inhibited binding to opioid and
      serotonin (5-HT) receptors at IC50 values between 0.4 and 3 microM, while
      hypericin and pseudohypericin inhibited with weaker potency. The biflavonoid
      I3,II8-biapigenin inhibited 3H-estradiol binding to the estrogen-alpha receptor
      with an IC50 value of 1 microM. The inhibition of 3H-muscimol binding to the
      GABA(A) receptor is likely to be exclusively due to GABA present in the extract.
      We therefore hypothesize that additive or synergistic actions of several ditsinct
      compounds may be responsible for the beneficial antidepressant effect of St.
      John's wort.

PMID- 11518064
TI  - Comparison of the effects of an alcoholic St. John's wort extract on various
      isolated organs.
AB  - We have studied the effects of a St. John's wort extract used in therapy on
      contractions of various isolated organ preparations induced by diverse
      spasmogens. Although it nonspecifically antagonized guinea pig ileum contractions
      induced by 7 different spasmogens, it had no effect on depolarization-induced
      contractions of rat aorta or those induced by acetylcholine, histamine or
      serotonin in the guinea-pig trachea. Spontaneous rhythmic contractions of rat
      portal veins were also not affected by the extract. Serotonin-induced
      contractions of rat aorta were most effectively inhibited by the agent. The
      observed effects of the extract were more prominent after it was washed out of
      the organ bath. Surprisingly, however, the extract also exerted negative
      inotropic and chronotropic effects on the rat atrium preparation. Our
      observations revealed several pharmacological properties of the Hypericum
      extract, and thus could be helpful in identifying and characterizing its active
      components and their modes of action.

PMID- 11518065
TI  - In vitro effects of St. John's wort extract and hyperforin on 5 HT uptake and
      efflux in human blood platelets.

PMID- 11518067
TI  - Batch-to-batch reproducibility of St. John's wort preparations.
AB  - Over the last few years, St. John's Wort products have enjoyed a tremendous surge
      in interest and sales for the therapy of mild to moderate depression. Although
      the complete spectrum of active substances in this herbal extract has not yet
      been elucidated, it is certain that hyperforin is an important component.
      Further, it appears that the hypericins may also contribute to the antidepressive
      activity. In this study, the content uniformity of eleven St. John's Wort
      products sold exclusively in pharmacies was determined. The main objective was to
      determine the batch-to-batch reproducibility of the various products. The
      hyperforin was analysed according to a previously published HPLC method, while
      the total hypericin content was determined by an electrochemical method. The
      results indicate that some, but not all, products show very reproducible batch-to
      batch properties. Also, individual products have different hypericin and
      hyperforin levels, and are therefore not switchable--even when products are
      manufactured under similar extraction and processing conditions, have the same
      raw material:extract ratios (on a dry basis) and contain the same amount of
      extract per unit dosage form.

PMID- 11518066
TI  - Evaluation of synaptosomal uptake inhibition of most relevant constituents of St.
      John's wort.
AB  - In our previous investigations, we could demonstrate that extract preparations of
      Hypericum perforatum (St. John's wort, SJW) inhibit the uptake of several
      neurotransmitters (serotonin, norepinephrine, dopamine, GABA, L-glutamate) in
      synaptosomal preparations of rodent brain. Hyperforin, the lipophilic
      constituent, was identified as the main component responsible for these effects.
      The properties seen for hyperforin in these and other pharmacological models
      present a plausible and logical explanation for the well documented
      antidepressive effects of SJW extract preparations in clinical studies. However,
      evidence for other active principles in SJW extract have been reported (See also
      communications by Misane & Ogren and Philippu in this issue). Accordingly, we
      tested various SJW extract preparations and all relevant constituents as possible
      inhibitors of synaptosomal uptake of neurotransmitters. Two further components
      were found to be active in those models. Adhyperforin, like hyperforin, showed a
      strong inhibiting profile in all uptake systems investigated. Moreover, we could
      observe a weak to moderate inhibiting profile for the oligomeric procyanidins
      fraction (OPC). Further investigations would have to clarify any possible
      contribution of these two constituents to the antidepressive effects of SJW
      extract seen in animal experiments and clinical trials.

PMID- 11518068
TI  - Pharmacological and endocrine effects of Hypericum perforatum and hypericin after
      repeated treatment.
AB  - Clinical studies have demonstrated the antidepressant efficacy of Hypericum (St.
      John's wort) extracts comparable to tricyclic antidepressants such as imipramine.
      We examined the effects of Hypericum extract and hypericin, one active
      constituent, in the forced swimming test (FST) after treatment repeated for 14
      days. It has recently been shown that hypericin was inactive in the FST after
      acute treatment, but remarkably active when solubilized by subfraction IIIc1
      containing mainly procyanidin B2. Therefore, we investigated the cooperative
      effects of hypericin and procyanidin B2 after repeated treatment. Imipramine (15
      mg/kg), Hypericum extract (500 mg/kg) and hypericin (0.1 mg/kg) given daily for 2
      weeks significantly reduced immobility time in the FST. No differences were
      observed between animals receiving pure hypericin and those receiving hypericin
      in combination with procyanidin B2. As several antidepressants act on the
      neuroendocrine axis resulting in altered hormone concentrations, selected
      endocrine parameters were investigated after repeated treatment. Daily treatment
      with either imipramine, Hypericum extract or hypericin alone or in combination
      with procyanidin B2 for 14 days significantly decreased plasma ACTH and
      corticosterone levels. None of the substances had pronounced effects on plasma
      prolactin or LH levels. From our present data, we propose that cooperative
      effects of hypericin and procyanidin B2 are of important relevance for the acute,
      but not for the chronic effects of this polycylic quinone.

PMID- 11518069
TI  - Comparative evaluation of Melissa officinalis L., Tilia europaea L., Passiflora
      edulis Sims. and Hypericum perforatum L. in the elevated plus maze anxiety test.
AB  - There are numerous plants that have been used for their 'tranquillising'
      properties in Portuguese folk medicine. This report will describe a comparative
      analysis of the effects of Melissa officinalis L., Tilia europaea L., Passiflora
      edulis Sims. and Hypericum perforatum L. on the performance of mice in the
      elevated plus maze, open-field, and horizontal-wire tests. We have tested
      lyophilised aqueous extracts with doses ranging from 5-100 mg/kg prepared
      according to traditional folk medicine. The results indicate that Hypericum
      perforatum L. and Tilia europaea L. induced significant raise in immobility time,
      diminution of rearing and other parameters, suggesting a clear sedative effect at
      doses ranging from 10-100 mg/kg. Below these doses, Tilia europaea L. did not
      induce any significant change in the tests mentioned, while Hypericum perforatum
      L. (5 mg/kg) increased the time spent in the open areas of the elevated plus maze
      and the percentage of unprotected head-dips and stretch-approach postures, thus
      indicating an anxiolytic effect. For this dose, there were no significant changes
      in motor activity as measured by classical parameters for the tests used. As the
      infused H. perforatum L. tested was devoid of hyperforin, it can be stated that
      the observed effects cannot be attributed to this substance.

PMID- 11518070
TI  - Effects of hyperforin on the fluidity of brain membranes.
AB  - Hyperforin, an acylphloroglucinol derivative isolated from Hypericum perforatum
      (St. John's wort, SJW), affects several ionic conductance mechanisms in brain
      cells by an as yet unknown mechanism. We tested the effects of hyperforin on the
      fluidity of crude brain membranes from young guinea pigs. We performed fluidity
      measurements with three different fluorescent probes. Diphenylhexatriene (DPH)
      and trimethylammonium-diphenylhexatriene (TMA-DPH) anisotropy measurements were
      inversely correlated with the flexibility of fatty acids in the membrane
      hydrocarbon core and in the hydrophilic area of membrane phospholipids,
      respectively. The ratio of pyrene excimer to monomer fluorescence intensities was
      used as an indicator of membrane annular and bulk fluidity. Incubation of brain
      membranes with relatively high concentrations of hyperforin sodium salt (10
      micromol/l) resulted in increased DPH and decreased TMA-DPH anisotropy,
      respectively, indicating that hyperforin modifies specific membrane structures in
      different ways. It decreases the flexibility of fatty acids in the membrane
      hydrocarbon core, but fluidizes the hydrophilic region of membrane phospholipids.
      Interestingly, relatively low concentrations of hyperforin (0.3 micromol/l)
      significantly decreased the annular fluidity of lipids close to membrane
      proteins. These findings are remarkable, as inhibition of several
      neurotransmitter-uptake systems and modulation of several ionic conductance
      mechanisms by hyperforin occur in the same concentration range. However, bulk
      fluidity was unchanged by this low hyperforin concentration. The results
      emphasise a physicochemical interaction of hyperforin with specific membrane
      structures that probably contribute to its novel pharmacological properties.

PMID- 11518071
TI  - Inhibition of substance P-induced cytokine synthesis by St. John's wort extracts.
AB  - We tested the hypothesis that extracts from St. John's wort interfere with
      protein synthesis induced by substance P (SP), a neuropeptide which has been
      implicated in the etiopathology of depression and anxiety. Using human
      astrocytoma cells, which express functional neurokinin (NK)-1-receptors, we
      investigated whether extracts from St. John's wort are able to inhibit SP-induced
      synthesis of the cytokine interleukin-6 (IL-6). We found a potent and dose
      dependent inhibition of SP-induced IL-6 synthesis by various extracts from St.
      John's wort. These results do not only give further evidence of the anti
      inflammatory effects of St. John's wort, but also lend support to the hypothesis
      that the antidepressant effect of St. John's wort is, at least in part, a result
      of its inhibitory effects on SP-induced protein synthesis.

PMID- 11518072
TI  - Researching the antidepressant actions of Hypericum perforatum (St. John's wort)
      in animals and man.
AB  - We have studied the effect of acute and sub-chronic treatments of a formulation
      of a methanolic extract of hypericum perforatum (HP, also known as St John's
      wort) on plasma hormones and brain neurotransmitters in healthy human volunteers
      and rats. Also studied were the effects of equivalent acute doses of two
      constituents of HP (with respect to LI 160 extract), hypericin and hyperforin in
      rats. In acute treatment studies in normal volunteers subjects received 9 tablets
      of the finished product Jarsin 300 and placebo in the pilot study (unblinded) and
      in the main study (a double blind, balanced order, cross-over design). Results in
      normal volunteer studies show that HP caused significant increases of salivary
      cortisol and plasma growth hormone (GH) whereas it decreased plasma prolactin
      versus placebo. Plasma hormone levels were associated with a rise in plasma
      hyperforin but not with hypericin, however no significant correlation was found.
      In the animal studies, acute treatment with LI 160, hyperforin and hypericin all
      caused significant increases in plasma corticosterone. This was associated with
      significant increases in brain cortical tissue 5-HT content. The corticosterone
      responses were attenuated by the 5-HT2 receptor antagonist, ketanserin but not by
      the 5-HT1A antagonist, WAY-100635. This suggests that the corticosterone
      responses may be mediated via a 5-HT2 mechanism of action. When sub-chronic and
      acute treatment using two different doses of LI 160 were compared, plasma
      corticosterone level were significantly decreased. Thus suggesting a down
      regulation or desensitisation of post-synaptic 5-HT2 receptors. Plasma prolactin
      was significantly reduced by acute treatment with LI 160 and hyperforin treatment
      but not by hypericin. This was associated with a concomitant rise in brain
      cortical tissue DA. Both LI 160 and hyperforin treatments decreased the plasma
      prolactin responses to the DA antagonist, haloperidol, suggesting that this may
      be associated with a DA-mediated mechanisn of action. When acute and sub-chronic
      treatments were compared, plasma prolactin responses were increased in the sub
      chronically treated animals. The studies when taken together suggest that the LI
      160 extract may effect plasma hormonal changes via both 5-HT and DA-mediated
      mechanisms but do not involve noradrenaline (NA). The data also suggests that
      hyperforin may be more important than hypericin for effecting these changes
      following acute treatment. Further studies investigating both acute and sub
      chronic effects of these compounds are necessary.

PMID- 11518073
TI  - Differential therapy of mild to moderate depressive episodes (ICD-10 F 32.0; F
      32.1) with St. John's wort.
AB  - The purpose of this report was to evaluate specific depressive symptoms that are
      most suitable for a therapy with the Ze 117 St. John's wort extract. We examined
      the antidepressant efficacy and drug safety of Ze 117 and fluoxetine in a
      multicentric prospective randomized double-blind parallel group comparison
      according to generally accepted guidelines such as the Declaration of Helsinki
      and GCP. We treated outpatients (n = 240; Ze 117: 126; fluoxetine: 114) with mild
      to moderate depressive episodes (ICD-10: F 32.0, F 32.1; HAMD range: 16-24) with
      either two tablets St John's wort (Ze 117; 500 mg extract/day) or fluoxetine (20
      mg/day) for 6 weeks. Antidepressant efficacy was evaluated with the validated
      HAMD psychometric method. A validated analysis of HAMD subscores was made to
      verify the efficacy for certain depressive symptoms. The main results were: * The
      HAMD responder rate was 60% in the Ze 117 group compared to 40% in the fluoxetine
      group (p = 0.005). * Particularly, there was a marked decrease of depressive
      agitation (pre-post comparison: 46%) and anxiety symptoms (44%) during the
      therapy with St. John's wort. Depressive obstruction (44%) and sleep disorders
      (43%) were reduced during the treatment, too. There were no statistically
      significant differences between the treatment groups. * Adverse events occurred
      in 28 patients (25%) in the fluoxetine group and in 18 (14%) of the St. John's
      wort group (p < 0.07). St. John's wort extract is a clinically effective
      equivalent to fluoxetine regarding overall depressive symptoms and main symptoms
      of depressive episodes. An especially interesting overall observation is that Ze
      117 is particularly effective in depressive patients suffering from anxiety
      symptoms. St. John's wort revealed better safety and tolerability data than
      fluoxetine.

PMID- 11518074
TI  - A study of the antidepressant activity of Hypericum perforatum on animal models.
AB  - The treatment of non-selected depressed patients with a hydro-alcoholic extract
      of Hypericum perforatum has been reported to have an efficacy similar to that of
      classical antidepressants. The effects of H. perforatum on three animal
      depression models have been studied: (a) an acute form of escape deficit (ED)
      induced by unavoidable stress; (b) a chronic model of ED, which can be maintained
      by the administration of mild stressors on alternate days; (c) a model of
      anhedonia based on the finding that repeated stressors prevent the development of
      appetitive behavior induced by vanilla sugar in satiated rats fed ad libitum. H.
      perforatum: (i) acutely protects animals from the sequelae of unavoidable stress;
      (ii) reverts the chronic escape deficit state maintained by repeated stressors
      and (iii) preserves the animal's capacity to acquire motivated appetitive
      behavior. Exposure to chronic stress not only induces escape deficit, but also
      decreases extraneuronal levels of dopamine in the nucleus accumbens shell; both
      behavioral and neurochemical effects are reverted by long-term treatment with
      antidepressants. Three-week treatment with H. perforatum reverted the chronic
      stress effect on extraneuronal dopamine in the nucleus accumbens. A consistent
      body of data in the literature suggests that, among the components of H.
      perforatum extract, hyperforin is the compound (or one of the compounds)
      responsible for the antidepressant activity. We compared the efficacy of the
      total extract with the efficacy of hyperforin after p.o. administration. In the
      acute-escape deficit model, hyperforin showed a potency of about ten times that
      of the total extract in protecting rats from the sequelae of unavoidable stress.
      Thus, hyperforin appears to be the most likely active component responsible for
      the antidepressant activity of H. perforatum.

PMID- 11518075
TI  - In vitro binding studies with two hypericum perforatum extracts--hyperforin,
      hypericin and biapigenin--on 5-HT6, 5-HT7, GABA(A)/benzodiazepine, sigma, NPY
      Y1/Y2 receptors and dopamine transporters.
AB  - Interactions between neurotransmitter receptors involved in the pathophysiology
      of depression, anxiety and ethanol consumption and two extracts (hydromethanolic
      and lipophilic extracts obtained with hypercritical CO2) from Hypericum
      Perforatum L or St. John's wort (SJW) and three constituents (hyperforin,
      hypericin and biapigenin) were evaluated by in vitro binding assays. The two
      extracts, tested at 10 microg/ml, did not inhibit ligand binding at the following
      receptors: serotonin 5-HT6 and 5-HT7, benzodiazepine, sigma and neuropeptide Y
      (NPY) Y1 and Y2 receptors. The hydromethanolic extract, but not the lipophilic
      extract, interacted with GABA(A) receptors (IC50 5.5 microg/ml), while both
      interacted with the dopamine (DA) transporters, albeit with high IC50 values
      (24.5 and 12.9 microg/ml, respectively). Biapigenin (1 microg/ml, 2 microM)
      inhibited ligand binding at benzodiazepine receptors only (IC50: 2 microM).
      Hyperforin (1 microg/ml, 2 microM) only inhibited [3H]WIN-35,428 binding to DA
      transporters, although the IC50 (5 microM) was higher than the IC50 found for
      inhibition of the synaptosomal DA reuptake (0.8 microM). This finding extended
      the same observation previously described for the 5-HTergic system to the DAergic
      system, confirming that the inhibition of monoamine reuptake is due to a
      different mechanism than that of synthetic antidepressants. Hypericin showed
      micromolar affinities for both NPY-Y1 and Y2 receptors and for sigma receptors
      (IC50 3-4 microM). These hypericin activities might be of interest because NPY
      and sigma receptors have been associated with anxiety disorders, depressive
      illnesses and ethanol consumption. However, they were present at relatively high
      hypericin concentrations, and were also light-dependent (i.e. the IC50 values
      increased when binding assays were carried out in the dark). Thus, our in vitro
      binding results may suggest that either the pharmacological effects of SJW are
      due to other molecules than hypericin or hyperforin (other constituents or active
      metabolites), or that the mechanism of action is different from those that have
      been considered up to now.

PMID- 11518076
TI  - Efficacy and tolerability of Ze 117 St. John's wort extract in comparison with
      placebo, imipramine and fluoxetine for the treatment of mild to moderate
      depression according to ICD-10. An overview.

PMID- 11518077
TI  - Hypericum perforatum--a review of clinical studies.
AB  - St. John's wort (Hypericum perforatum) has been used as a medicinal herb for over
      2000 years. Over the past 2 decades, its application as a plant extract for
      treating depression has undergone rigorous scientific investigation, and its
      effectiveness has been shown in studies comparing it with placebo and preference
      antidepressants. Safety and tolerability studies have revealed that St. John's
      wort (SJW) preparations have better safety and tolerability profiles than
      synthetic antidepressants. The indications for St. John's wort preparations
      comprise patients with mild or moderate depression. Based on the existing
      literature, limitations to efficacy in more severe cases as well as interactions
      and contraindications have to be respected.

PMID- 11518078
TI  - St. John's wort extract Ze 117 (Hypericum perforatum) inhibits norepinephrine and
      serotonin uptake into rat brain slices and reduces 3-adrenoceptor numbers on
      cultured rat brain cells.
AB  - Despite almost forty years of widespread use, the mode of action of
      antidepressant drugs is still largely unknown. There is agreement that these
      drugs interact with central neurotransmission. Common findings are acute
      inhibitory actions on reuptake mechanisms for norepinephrine (NE) and for
      serotonin (5-HT) at presynaptic axons and chronic adaptive effects on
      neurotransmitter receptors on postsynaptic membranes. In particular, beta
      adrenoceptor downregulation has been observed after chronic treatment with most
      antidepressants in vivo and in cell culture systems. We studied the effectiveness
      of Ze 117 (St. John's wort) extract (Hypericum perforatum) on NE- and 5-HT-uptake
      into rat brain slices. Potency and efficacy of the Ze 117 extract were compared
      with those of tricyclic (TCA) and selective serotonin reuptake inhibitor (SSRI)
      type antidepressants. A dose-dependent inhibition was seen on NE and 5-HT uptake
      into brain slices. The Ze 117 extract was more selective for the uptake of NE
      than for that of 5-HT. The maximal extent of uptake inhibition by Ze 117 extract
      was comparable to that of imipramine (IMI), desipramine (DMI) or fluvoxamine for
      5-HT, but lower for NE transport, than that of the synthetic antidepressants.
      Chronic exposure (8 days) of confluent C6-cell cultures to Ze 117 extract
      resulted in a dose-dependent beta-adrenoceptor downregulation equal to that
      induced by DMI, a potent TCA. None of these effects could be achieved with either
      hypericin or hyperforin alone in a relevant dose range. Our results indicate that
      the St. John's wort extract Ze 117 contains active, but as yet unknown
      antidepressant principles with effects comparable to those of TCAs.

PMID- 11518079
TI  - Hypericum extract and hyperforin: memory-enhancing properties in rodents.
AB  - Effects of a Hypericum extract in therapeutic use and hyperforin sodium salt were
      evaluated in rat and mouse avoidance tests. In a conditioned avoidance response
      (CAR) test on the rat, oral daily administration of hyperforin (1.25 mg/kg/day)
      or of the extract (50 mg/kg/day) before the training sessions considerably
      improved learning ability from the second day onwards until the day 7. In
      addition, the memory of the learned responses acquired during 7 consecutive days
      of administration and training was largely retained even after 9 days without
      further treatment or training. The observations made using different doses
      indicate that these learning-facilitating and/or memory-consolidating effects by
      the agents follow inverse U-shaped dose-response curves in dose ranges lower than
      (for hyperforin) or equal to (for Hypericum extract) their effective dose in the
      behavioral despair test for antidepressants. In a passive avoidance response test
      on the mouse, a single oral dose (1.25 mg/kg) of hyperforin not only improved
      memory acquisition and consolidation, but also almost completely reversed
      scopolamine-induced amnesia. The single Hypericum extract dose tested (25 mg/kg)
      did not reveal any significant effects in the passive avoidance response (PAR)
      test on the mouse. These observations suggest that the Hypericum extract could be
      a novel type of antidepressant with memory enhancing properties, and indicate
      that hyperforin is involved in its cognitive effects. Pure hyperforin seems to be
      a more potent antidementia agent than an antidepressant.

PMID- 11518080
TI  - Hyperforin stimulates intracellular calcium mobilisation and enhances
      extracellular acidification in DDT1-MF2 smooth muscle cells.
AB  - Hyperforin, an acylphloroglucinol derivative, is a major constituent of St.
      John's wort extract (Hypericum perforatum L.), which is used in treating
      depressive disorders. Hyperforin has been demonstrated as a modulator of several
      neuronal ion channels, and inhibits smooth-muscle contraction induced by various
      neurotransmitters. To evaluate the spasmolytic properties of hyperforin in more
      detail, we performed studies on the hamster vas deferens smooth muscle cell line
      DDT1-MF2. In a first series of experiments, we determined the effect of
      hyperforin on intracellular Ca2+ concentration ([Ca2+]i) using the fluorochrome
      fura-2. These investigations were supplemented in a second series of assays,
      where the effects on cellular metabolism were analysed by measuring the rate of
      extracellular release of acidic metabolites with the help of a microphysiometer.
      Hyperforin (0.3-10 microg/ml) caused a concentration-dependent elevation of
      [Ca2+]i and extracellular acidification rate (ECAR). Both of these effects were
      independent of extracellular Ca2+. To elucidate whether the increase of [Ca2+]i
      by hyperforin causes or results from its ECAR-stimulating properties, we used
      various pharmacological tools to reveal the sequence of events and the molecular
      mechanisms involved. Our results suggest that hyperforin induces release of Ca2+
      from as yet unidentified sources. Since the ECAR stimulation was inhibited to a
      different extent by the intracellular Ca2+ chelator BAPTA as well as by
      inhibitors of plasmalemmal and mitochondrial Na+/Ca2+ exchange, but not by
      inhibitors of Na+/H+ antiport, the intracellular Ca2+ increase seems to be
      essential for this hyperforin effect. However, further studies are needed to
      establish the exact mode of action, and to deduce whether this aspect of
      hyperforin activity contributes to its antidepressant and neuroprotective
      effects.

PMID- 11518081
TI  - Modulation of ion channels in rat neurons by the constituents of Hypericum
      perforatum.
AB  - Despite almost forty years of widespread use of antidepressant drugs, their mode
      of action is still unknown. Hyperforin, a phloroglucinol derivative, is a major
      pharmacologically and therapeutically active constituent of Hypericum perforatum
      extract that is widely used as an herbal antidepressant drug. However, the
      mechanism or mechanisms of action of these naturally abundant, non-toxic extracts
      remain unclear. Enzymatically isolated patch-clamped rat central and peripheral
      neurons exposed to rapid changes in the composition of external medium
      (concentration clamp) were used in our experiments to investigate the modulation
      of the various voltage- and ligand-gated channels by hyperforin, as well as by
      other constituents of Hypericum perforatum. At nanomolar concentrations,
      hyperforin induced significant inhibition of various ion channels. In the case of
      P-type Ca2+ channels, we established that hyperforin acts via interaction with
      calmodulin or through calmodulin-activated pathways involving at least one second
      messenger. The results presented here indicate that multiple mechanisms and
      extract constituents may be involved in the antidepressant action of Hypericum
      extracts, and that they could also possess neuroprotective and analgesic effects.

PMID- 11518082
TI  - Interleukin-6 involvement in antidepressant action of Hypericum perforatum.
AB  - Hypericum, a plant widely used as antidepressant has been shown to interact with
      the immune system. We studied the effects of the administration of the Hypericum
      perforatum extract Ph-50, a Hypericum extract, standardized to flavonoids (50%)
      and containing 0.3% of hypericin and 4.5% of hyperforin in a forced swimming test
      and tryptophan, serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA)
      diencephalic content using a high performance liquid chromatography method in
      male interleukin-6 (IL-6) knock-out (IL-6(-/-)) and wild type (IL-6(+/+)) mice.
      Hypericum extract (Ph-50; 500 mg/kg) oral acute administration reduced the
      immobility time of wild type, but not of knockout mice. Tryptophan content was
      not modified by Hypericum in all the animal groups. Serotonin and 5-HIAA
      diencephalic content was increased by Hypericum in both wild type and knockout
      mice. However, the increase observed in the wild type was greater than in
      knockout mice. These data indicate that IL-6 could be necessary to the
      antidepressant action of Hypericum, and that this cytokine (probably) mediates
      the effects of Hypericum through activation of the serotonin system.

PMID- 11518083
TI  - Effects of Hypericum perforatum L. on evoked potentials in guinea pig hippocampal
      slices.
AB  - Therapeutic uses of Hypericum extracts have been demonstrated as safe and
      effective in treating mild to moderate depression in numerous clinical trials. To
      date, however, no definitive statements on their mode of action can be made, and
      little information on their electrophysiological effects is available. The
      present communication summarises the results of our efforts directed towards
      clarifying the effects of an ethanolic Hypericum extract (HYP) and its
      hydrosoluble fraction (HYPWS), and two of its constituents hypericin and
      hyperforin on electrically evoked population spikes in guinea pig hippocampal
      slices. In higher concentrations (>10 microM), the two extract constituents
      tested revealed inhibitory effects only, whereas concentration-dependent (between
      10(-6) to 10(-4) g/l) excitatory effects were observed for HYP and HYPWS. The
      excitatory effects were strongly amplified by the GABA(B) antagonist phaclofen,
      whereas the effects of bicucullin, a GABA(A) antagonist, were marginal. The
      excitations were completely blocked by the AMPA antagonist CNQX, but not by the
      NMDA antagonists APV and MK801 or the L-type calcium-channel blocker verapamil.
      This kind of excitatory effect on the hippocampus is unknown in other
      antidepressants and; indeed, many of the latter reduce neuronal excitability. We
      conclude, therefore, that the mechanisms involved in the antidepressant activity
      of Hypericum extracts are different from those of conventional antidepressants,
      and that identifying their excitatory components may facilitate their more
      rational standardisation.

PMID- 11518084
TI  - Effects of Hypericum perforatum (St. John's wort) on passive avoidance in the
      rat: evaluation of potential neurochemical mechanisms underlying its
      antidepressant activity.
AB  - Along with traditional pharmacotherapies, extracts of Hypericum perforatum L.
      (St. John's wort) are used in the treatment of mild to moderately severe
      depression. Hypericum is a nonspecific inhibitor of the neuronal uptake of
      monoamines (serotonin, 5-HT; noradrenaline, NA; dopamine, DA) as well as GABA and
      glutamate. Hypericum extracts have been shown to be active in several different
      "animal models for antidepressant drugs". As one of a large number of chemical
      constituents, the phoroglucinol derivative hyperforin might be an important
      "antidepressant component" of hypericum. However, the exact role of neurochemical
      mechanisms underlying in vivo actions of hypericum and hyperforin are not well
      defined. In the present study, we compared the effects of hypericum, hyperforin
      and hyperforin-free hypericum and the three conventional antidepressants
      paroxetine, imipramine and desipramine using the passive avoidance (PA) task in
      the rat. The 5-HT-releasing compound p-chloroamphetamine (PCA), which operates
      through the 5-HT neuronal transporter, was used to reveal the potential in vivo
      effects on 5-HT uptake mechanisms. To examine the ability of the test-compounds
      to enhance noradrenaline (NA) transmission in vivo, subeffective doses of
      scopolamine were used. Taken together, our results suggest that (1) hypericum
      given at high doses can probably affect the neuronal 5-HT uptake mechanisms in a
      manner more reminiscent of TCAs than SSRIs; (2) similar to TCAs and SSRIs,
      hypericum and hyperforin are active in the scopolamine test. Hyperforin appears
      to play a major role in the action of hypericum in this model. Both 5-HT and NA
      might concomitantly contribute to the effects of different antidepressants in the
      "low-dose scopolamine" model; (3) hypericum might enhance both 5-HT and NA
      transmission in forebrain limbic brain circuits important for mood control, which
      could underly its antidepressant effects. However, the relative contribution of
      different constituents and exact mechanisms of action require further evaluation.

PMID- 11518085
TI  - Hyperforin--antidepressant activity by a novel mechanism of action.
AB  - Hyperforin represents a major antidepressive constituent of St. John's wort (SJW)
      extract. It not only inhibits the neuronal uptake of serotonin, norepinephrine
      and dopamine like many other antidepressants, but also inhibits GABA and L
      glutamate uptake. This broad-spectrum effect is obtained by an elevation of the
      intracellular Na+ concentration, probably due to activation of sodium conductive
      pathways not yet finally identified but most likely ionic channels. This makes
      hyperforin the first member of a new class of compounds with a preclinical
      antidepressant profile due to a completely novel mechanism of action.

PMID- 11518086
TI  - Regulation of drug intake.
AB  - Regulation of drug intake refers to the maintenance of relatively constant levels
      of drug over a specified time period. An understanding of regulation of drug
      intake may be critical in determining how drugs function as reinforcers and how
      their reinforcing effects may be modified. However, little is known about
      regulation of drug intake, and the mechanisms underlying it are poorly
      understood. Three mechanisms that have proposed to account for findings of
      regulation of drug intake were discussed to determine their relevance for drug
      reinforced responding. These mechanisms include aversive effects, direct effects,
      and satiation. Although a greater role for satiation was supported in this
      review, drugs may vary on the degree to which they can produce satiation and
      whether satiation acts in concert with either the aversive effects or the direct
      effects of drugs is unclear.

PMID- 11518087
TI  - No thanks, I'm good. Any more and I'll be sick: comment on Lynch and Carroll
      (2001).
AB  - W. J. Lynch and M. E. Carroll's (2001) excellent analyses of drug intake from a
      regulation perspective are formalized in terms of control systems. Satiation
      corresponds to the set point, deviations below which are called hunger or
      craving, deviations above which are called surfeit. Although simple, the model
      provides a unifying framework for many of the phenomena Lynch and Carroll
      describe.

PMID- 11518088
TI  - Drug-intake regulation and the interplay between economic costs and benefits:
      comment on Lynch and Carroll (2001).
AB  - W. J. Lynch and M. E. Carroll's (2001) review argues against aversive effects and
      for satiation and direct effects as the mechanisms responsible for the descending
      limb of the dose-response function. Analysis is provided that suggests they may
      prematurely dispose of the aversive-effects account. Further analysis of the
      evidence for satiation and direct effects supports the authors' contention that
      neither can be exclusively supported. A brief behavioral-economic analysis of
      drug-intake regulation and the descending limb of the dose-response function is
      presented.

PMID- 11518089
TI  - Satiety threshold regulates maintained self-administration: comment on Lynch and
      Carroll (2001).
AB  - In this commentary the authors argue that the satiety threshold is the only
      mechanism that is sufficient and necessary to explain the regulation of
      maintained self-administration. The other mechanisms have been proposed mainly
      because of 2 sources of confusion surrounding the self-administration paradigm:
      the failure to distinguish between separate phases of a self-administration
      session and the assumption that positive reinforcement underlies drug self
      administration. The authors of this commentary emphasize that the direct effects
      and aversion mechanisms have been proven to be untenable for the reasons reviewed
      by W. J. Lynch and M. E. Carroll (2001) and that the "ascending limb" of the dose
      response curve is an experimental artifact. These ideas have persisted only to
      salvage a role for positive reinforcement in drug self-administration. The
      authors conclude that reinforcement is not relevant to the regulation of
      maintained self-administration.

PMID- 11518090
TI  - How does regulation of drug intake come about? Comment on Lynch and Carroll
      (2001).
AB  - W. J. Lynch and M. E. Carroll (2001) suggested 3 processes that contribute to the
      regulation of drug intake over time when drugs serve as reinforcers. The
      commentator suggests that none of these processes are necessary for drugs to
      function as reinforcers and hence are either secondary or superfluous to the
      study of drugs as reinforcers.

PMID- 11518091
TI  - Access conditions are crucial: comment on Lynch and Carroll (2001).
AB  - W. J. Lynch and M. E. Carroll (2001) sought to identify factors that control drug
      intake, that is, factors that decrease the avidity of drug seeking and drug
      taking while drug is obviously available. The review provides updated information
      about factors that regulate drug intake and a heuristic framework for future
      studies of regulatory processes throughout the natural history of a substance
      abuse disorder. In particular, the review suggests a productive framework for
      studies of transitions from early drug use to later abusive use. Forceful
      identification of factors that control the avidity of drug seeking and drug
      taking under the controlled conditions of the laboratory may encourage
      development of therapeutic interventions that capitalize on these factors for
      successful treatment of human drug abuse. Extending the analysis of regulation of
      intake to include factors that can be manipulated to reorganize behavior may
      improve the design of interventions to treat drug abuse.

PMID- 11518092
TI  - Dose-response effects of methylphenidate on ecologically valid measures of
      academic performance and classroom behavior in adolescents with ADHD.
AB  - The effects of methylphenidate on the academic performance and classroom behavior
      of 45 adolescents with attention deficit hyperactivity disorder were studied.
      During a 6-week, placebo-controlled medication assessment in the context of a
      summer treatment program, participants received a double-blind, crossover trial
      of 3 doses of methylphenidate. Dependent measures included note-taking quality,
      quiz and worksheet scores, written language usage and productivity, teacher
      ratings, on-task and disruptive behavior, and homework completion. Group data
      showed positive effects of methylphenidate on academic measures; however, the
      greatest benefit came with the lowest dose. Although additional benefit did occur
      for some participants with higher doses, the largest increment of change usually
      occurred between the placebo and 10-mg dose. Many adolescents did not experience
      added benefit with increased dosages, and in some cases they experienced
      deterioration. Guidelines for assessment of medication effects are discussed.

PMID- 11518094
TI  - The cue-availability paradigm: the effects of cigarette availability on cue
      reactivity in smokers.
AB  - Researchers have hypothesized that drug availability should influence addicts'
      reactions to drug-related stimuli, but manipulations of the extent to which drug
      users have access to their drugs following a session of exposure to drug cues
      have not produced strong availability effects. This study used within-session
      manipulations of drug availability to examine cigarette smokers' reactions to
      smoking cues. Smokers (N = 60) were exposed to 48 trials of either a lit
      cigarette or a glass of water while they were informed of the probability (0%,
      50%, or 100%) that they would be able to consume the cue on each trial. Results
      from measures of craving, mood, skin conductance, and latency to access the cues
      indicated that the trial-by-trial manipulation of drug availability had a
      pronounced impact on reactivity to cigarette cues.

PMID- 11518093
TI  - Do adolescent smokers experience withdrawal effects when deprived of nicotine?
AB  - This is the first controlled prospective study of the effects of nicotine
      deprivation in adolescent smokers. Heart rate and subjective withdrawal symptoms
      were measured over an 8-hr period while participants smoked normally. Seven days
      later, participants were randomized to wear a 15-mg (16-hr) nicotine patch or a
      placebo patch for 8 hr, and they refrained from smoking during the session. Those
      wearing the placebo experienced a decrease in heart rate across sessions and an
      increase in subjective measures of nicotine withdrawal. Those wearing the active
      patch also reported significant increases for some subjective symptoms.
      Expectancy effects were also observed. The findings indicate that adolescent
      smokers experience subjective and objective changes when deprived of nicotine. As
      in previous research with adults, expectancies concerning the effects of nicotine
      replacement also influenced perceptions of withdrawal.

PMID- 11518095
TI  - Benzodiazepine modulation of opiate reward.
AB  - Case studies reveal that opiate addicts often premedicate themselves with
      benzodiazepine (BDZ) tranquilizers prior to taking their opiate. It has been
      hypothesized that such actions occur because the BDZ enhances the euphoric or
      reinforcing properties of the opiate. The present study tested this hypothesis in
      the animal laboratory. Sprague-Dawley rats were used to examine whether the
      magnitude of conditioned preferences for a distinctive environment associated
      with intravenous heroin delivery would be augmented by intraperitoneal alprazolam
      pretreatment. Results demonstrated that alprazolam produced a leftward shift of
      the heroin dose-response curve in the conditioned place preference test. The data
      obtained are consistent with the view that BDZs can augment the affective
      response to heroin in laboratory animals.

PMID- 11518096
TI  - Effects of chronic morphine treatment on responding for intracranial stimulation
      in female versus male rats.
AB  - Morphine was administered to Sprague-Dawley rats twice daily at 0, 3, 10, and 20
      mg/kg/ injection during Weeks 1, 2, 3, and 4, respectively; responding for medial
      forebrain bundle stimulation was assessed 1, 2, and 3 hr after morning injections
      in female versus male rats. There were no sex differences in responding under
      control conditions (Week 1). Morphine's effect on response rate depended on dose,
      time post-injection, stimulation frequency, and day of treatment. Significant sex
      differences in morphine's effects occurred at 10 mg/kg, which decreased
      responding more in males at 1 hr and increased responding more in females at 2
      hr, at some frequencies and on some test days. Similar trends were observed at
      other frequencies, test days, and doses. Morphine's differential effect in males
      versus females in this procedure suggests that sex comparisons of opioid effects
      in many animal models may be influenced by sex differences in opioid effects on
      behavioral output.

PMID- 11518097
TI  - Behavioral measurement of thermal pain sensitivity in humans: effects of stimulus
      intensity and instructions.
AB  - This study validated a human behavioral model of thermal nociception analogous to
      the rodent tail-flick assay. Effects of instructions and stimulus intensity on
      behavior (i.e., finger withdrawal latency) were evaluated. Using a repeated
      measures randomized crossover design, the authors exposed 10 volunteers to
      varying radiant heat intensities (from 42.2 to 52.2 degrees C) during each of
      four sessions. In the different sessions, participants were told to remove their
      finger when they felt heat, felt unpleasant, felt pain, or could no longer
      tolerate pain. Withdrawal latencies significantly decreased as stimulus intensity
      increased and significantly increased for sensory, affective, pain, and
      intolerance instructions. Instruction set differences were significantly larger
      at higher stimulus intensities. This technique may be useful in human
      psychopharmacological research.

PMID- 11518098
TI  - Constructive thinking, executive functioning, antisocial behavior, and drug use
      involvement in adolescent females with a substance use disorder.
AB  - The main aim of this study was to determine how constructive thinking (CT),
      executive functioning (EF), and antisocial behavior (ASB) are related to drug use
      involvement in 282 adolescent females, 14-18 years of age, with a substance use
      disorder (SUD) and in controls. CT was measured using the Constructive Thinking
      Inventory (S. Epstein & P. Meier, 1989), EF was measured using a battery of
      neuropsychological tests, and ASB was measured using the Youth Self-Report
      Inventory (T. Achenbach, 1991) and a psychiatric interview. Females with an SUD
      demonstrated lower CT and EF scores and higher ASB scores compared with the
      controls. Low CT and low EF were significantly related to increased drug use
      involvement even when controlling for age, socioeconomic status, and vocabulary
      level. ASB partially mediated the relation between CT and drug use involvement,
      and it fully mediated the relation between EF and drug use involvement. Moreover,
      ASB moderated the relation between EF and drug use involvement.

PMID- 11518100
TI  - Should B-RTO be the first-line treatment for portosystemic encephalopathy?

PMID- 11518099
TI  - Inhibition of nicotine-induced seizures in rats by combining vaccination against
      nicotine with chronic nicotine infusion.
AB  - The ability of a nicotine vaccine to protect against nicotine-induced seizures
      was studied in rats. Groups of 10 rats were vaccinated with 3 doses of either a
      nicotine conjugate vaccine over 6 weeks to elicit high titers of nicotine
      specific antibodies or with a control vaccine. Rats were then pretreated with a 1
      week subcutaneous infusion of either nicotine 1 mg/kg/day or saline and then
      received a single 2 mg/kg ip dose of nicotine to provoke seizures. Vaccination
      reduced the incidence of seizures. The combination of vaccination and
      pretreatment with nicotine infusion was more effective than either treatment
      alone. These data suggest that vaccination is protective against this toxic
      effect of nicotine and that combining vaccination and chronic nicotine
      administration may provide a novel strategy for blocking some effects of
      nicotine.

PMID- 11518101
TI  - The prognosis of IgA nephropathy--favorable or poor?

PMID- 11518102
TI  - Molecular biology of polycythemias.
AB  - Polycythemia is literally translated as "many cells in the blood". Only
      erythrocytosis (an alternative term for these disorders) produces polycythemia
      since leukocytes and platelets are present in blood in far smaller proportions.
      Polycythemia may be due to increased proliferation or decreased apoptosis of
      erythroid progenitors, or to delayed erythroid differentiation with an increased
      number of progenitor cell divisions. Prolonged red cell survival, another
      theoretical cause of polycythemia, has not yet been described and with intact
      regulatory mechanisms is unlikely to occur. Primary polycythemias result from
      abnormalities expressed in hematopoietic progenitors. In contrast, circulating
      factors cause secondary polycythemia (1). There are acquired and congenital
      causes of both primary and secondary polycythemia (1).

PMID- 11518103
TI  - Therapeutic effect of balloon-occluded retrograde transvenous obliteration on
      portal-systemic encephalopathy in patients with liver cirrhosis.
AB  - OBJECTIVE: Balloon-occluded retrograde transvenous obliteration (B-RTO) has
      recently been introduced as a new interventional modality to prevent fatal
      bleeding from solitary gastric varices. A large portal-systemic shunt including
      gastric varices also causes severe encephalopathy in some cirrhotic patients. In
      this study, we evaluated the effect of B-RTO as a candidate therapeutic method to
      treat chronic recurrent hepatic encephalopathy due mainly to a portal-systemic
      shunt. PATIENTS AND METHODS: Since July 1995, we experienced 43 cirrhotic
      patients with chronic reccurent hepatic encephalopathy. Among them, six patients
      had anigographically proven large (>1 cm in diameter) portal-systemic shunt, and
      received B-RTO. B-RTO was carried out only once using 5% ethanolamine oleate with
      iopamidole to obliterate the portal-systemic shunt for 30 minutes. The median
      observation period after B-RTO was 29 months (range 23-46 months). RESULTS: In
      all 6 patients, encephalopathy had disappeared after B-RTO, and the patients were
      free of encephalopathy during the following 6 months. B-RTO significantly reduced
      blood ammonia levels at one month, 3 months, and 6 months later, without
      affecting serum aspartate aminotransferase activity, total bilirubin and albumin
      concentrations, and plasma prothrombin time. Encephalopathy relapsed in 4
      patients between 6 and 30 months. Additional B-RTO was required and effective in
      2 of them. CONCLUSION: B-RTO is an effective treatment for chronic recurrent
      hepatic encephalopathy with an angiographically proven portal-systemic shunt.

PMID- 11518104
TI  - Alcohol consumption as a major risk factor in the development of early esophageal
      cancer in patients with head and neck cancer.
AB  - OBJECTIVE: To clarify the incidence of concomitant esophageal cancers in patients
      with head and neck cancer (HNC), and to investigate which risk factors are
      responsible for this association. PATIENTS AND METHODS: From 1994 to 2000, 134
      patients with HNC underwent upper gastrointestinal endoscopy using the 0.8% Lugol
      stain method to detect esophageal cancer. A case-control study was designed to
      compare HNC patients with and without esophageal cancer. Logistic-regression
      analysis was used to obtain odds ratios of risk factors. RESULTS: Out of 134
      patients with HNC, Lugol unstained area was detected in 42 patients. Biopsy
      specimens revealed squamous cell carcinoma in 17 (12.7%), dysplasia in 9 patients
      (6.6%), and normal in the others. Gastric carcinoma was also detected in 7
      patients (5.2%). The estimated depth of cancer invasion was mucosa in 9 patients,
      submucosa in 5 patients, and proper muscle or deeper in 3 patients. In the
      results of statistical analysis, high alcohol consumption of more than 75 g per
      day increased the risk of esophageal cancer (odds ratio: 20.2, p<0.01). Intake of
      hard liquor showed a high odds ratio (whisky: 28.7, p<0.05, shochu: 12.7,
      p<0.05). The amount of cigarette smoking was not related to this association.
      CONCLUSION: High incidence of esophageal cancer was found in the patients with
      HNC. A high alcohol consumption level, and in particular hard liquor,
      participated in the development of esophageal cancer in the patients with HNC.
      But cigarette smoking was not related to this association.

PMID- 11518105
TI  - Heterogeneity of prognosis in adult IgA nephropathy, especially with mild
      proteinuria or mild histological features.
AB  - OBJECTIVE: The present study was undertaken to clarify the clinical course and
      prognosis of adult patients with primary IgA nephropathy (IgAN), especially with
      mild proteinuria or mild histological alternations. PATIENTS AND METHODS: A
      population of 735 IgAN patients whom we were able to observe for more than two
      years was examined. RESULTS: A total of 115 patients (15.6%) was on dialysis
      during the observation period. The overall 5-year renal survival rate was 92.0%.
      On the other hand, 166 patients (22.6%) were in clinical remission. A group with
      mild proteinuria included 197 patients (26.8%). Forty-seven patients of this
      group showed minor glomerular abnormalities, whereas 12 patients with mild
      proteinuria showed severe mesangial involvement. Three patients with mild
      proteinuria were on dialysis during the observation period, whose proteinuria was
      increased during the clinical course. A group with minor glomerular abnormalities
      included 82 patients (11.2%). Forty-seven patients of this group showed mild
      proteinuria, of whom 12 patients showed moderate proteinuria. However, three
      patients with minor glomerular abnormalities who were not on dialysis showed loss
      of renal function. CONCLUSION: These results indicated the heterogeneity of the
      course and prognosis in IgAN. Even if a patient's initial clinical or
      histological findings are comparatively mild, strict follow-up management is
      needed.

PMID- 11518106
TI  - Clinical analysis of community-acquired pneumonia in the elderly.
AB  - OBJECTIVE: To evaluate the clinical features, etiology, and outcome of patients
      over 65 years old hospitalized for community-acquired pneumonia. PATIENTS: Eighty
      four patients (50 males, 34 females) hospitalized for community-acquired
      pneumonia in Kawasaki Medical School Kawasaki Hospital between April 1998 and
      March 2000. RESULTS: Most of the patients had respiratory symptoms or signs, but
      over one-third also had atypical symptoms of pneumonia such as dyspnea,
      consciousness disturbance, and gastrointestinal symptoms. The causative
      microorganisms were identified in 48% of these patients. Streptococcus pneumoniae
      (13%), respiratory viruses (13%), Haemophilus influenzae (8%) and Mycobacterium
      tuberculosis (8%) were frequently identified, but Mycoplasma pneumoniae was less
      frequently noted in the elderly. Double infection was recognized in 19 % and a
      combination of some virus and bacteria in 13%. Treatment consisted of the
      administration of second or third generation cephalosporin antibiotics
      intravenously, because antibiotics had already been preadministered in 39%. The
      prognosis was poor (mortality rate 9%) for the elderly with community-acquired
      pneumonia despite mechanical ventilation in 8%. CONCLUSIONS: Although the range
      of microorganisms causing community-acquired pneumonia differed slightly from
      that in previous reports; namely, lower frequency of Chlamydia pneumoniae and
      Legionella pneumophila, it is suggested that the initial antibiotic treatment
      should always cover S. pneumoniae and H. influenzae. In addition, since a
      prevalence of virus infections related to the increase in community-acquired
      pneumonia in the elderly was found in this study, the routine use of influenza
      vaccine and pneumococcal vaccines in the elderly is recommended to reduce the
      high mortality rate.

PMID- 11518107
TI  - Progressive renal failure and blindness due to retinal hemorrhage after
      interferon therapy for hepatitis C virus-associated membranoproliferative
      glomerulonephritis.
AB  - We treated a 67-year-old Japanese woman with membranoproliferative
      glomerulonephritis (MPGN) and chronic active hepatitis associated with hepatitis
      C virus (HCV) infection. Treatment commenced with a daily dose of 6 MU IFN alpha
      2b for 2 weeks, which was changed to three times weekly thereafter. After 2
      weeks, HCV RNA in the serum was undetectable and there was a concomitant
      reduction in proteinuria. Treatment with IFN alpha-2b was discontinued because of
      severe headache and fever. Five weeks after the discontinuation of IFN alpha-2b,
      the patient experienced the sudden onset of visual loss due to retinal
      hemorrhage. Subsequently, proteinuria and renal function progressively
      deteriorated though HCV RNA was undetectable. This case exemplifies the need for
      careful monitoring of renal function and retinal lesions not only in patients
      receiving IFN but also in those following the discontinuation of IFN treatment.

PMID- 11518108
TI  - Superior mesenteric artery syndrome in identical twin brothers.
AB  - We report two identical male twins who suffered from superior mesenteric artery
      (SMA) syndrome. A 28-year-old man was admitted for investigation of postprandial
      nausea and vomiting. Upper gastrointestinal examination revealed a dilated
      proximal duodenum with an abrupt vertical cutoff of barium flow in the third
      portion of the duodenum, establishing the diagnosis of SMA syndrome. One year
      later, his twin brother also presented similar symptoms and was radiologically
      diagnosed as SMA syndrome. The twin brothers did not respond adequately to
      conservative therapy and underwent duodenojejunostomy. This is the first report
      of SMA syndrome in identical twins.

PMID- 11518109
TI  - Initiation of enzyme replacement therapy for an adult patient with asymptomatic
      type 1 Gaucher's disease.
AB  - A 27-year-old woman was admitted for further examination of thrombocytopenia.
      Symptoms were absent, but physical examination demonstrated hepatosplenomegaly
      without neurological abnormalities. Bone marrow examination revealed many Gaucher
      cells, and glucocerebrosidase activity from cultured skin fibroblasts was
      markedly reduced. A 1448C (L444P) mutation was detected on one allele of the
      glucocerebrosidase gene. Because magnetic resonance imaging (MRI) of the femora
      indicated severe infiltration of Gaucher cells into bone marrow, enzyme
      replacement therapy was initiated despite the absence of skeletal symptoms.
      Hematologic abnormalities, visceral and bone involvement have been improving. In
      cases of thrombocytopenia or hepatosplenomegaly, Gaucher's disease should be
      suspected.

PMID- 11518110
TI  - Aortic aneurysm involving a right-sided arch complicating aortobronchopulmonary
      and aortoesophageal fistula.
AB  - A 66-year-old man with hemoptysis, chest pain, fever, and hoarseness was admitted
      to our department. A right-sided aortic arch and three aneurysms in the proximal
      arch, distal arch, and descending aorta were confirmed by aortography and
      surgery. Fistula formations were discovered between the proximal arch aneurysm
      and the right upper lobe (aortobronchopulmonary fistula: ABF), and between the
      descending aorta and the esophagus (aortoesophageal fistula: AEF). Concomitant
      ABF and AEF are very rare. Aortopulmonary and/or aortoesophageal fistula
      complicated by a right-sided aortic arch have not been previously reported.

PMID- 11518111
TI  - Crow-Fukase syndrome with ischemic cardiomyopathy.
AB  - A 31-year-old man was admitted to our hospital for further evaluation of heart
      failure symptoms. Crow-Fukase syndrome was diagnosed on the basis of findings of
      polyneuropathy, hepatomegaly, monoclonal hypergammaglobulinemia, and
      hypertrichosis. Dipyridamole-stress thallium-201 perfusion imaging, contrast left
      ventriculography, and coronary angiography revealed a markedly dilated and
      dysfunctioning left ventricle, extensive reversible ischemia with fixed defect,
      and multiple coronary lesions. Histopathology of myocardial biopsy specimens
      demonstrated ischemia-induced myocardial necrosis. These findings suggested that
      ischemic cardiomyopathy, probably due to inflammatory reactions of coronary
      arteries in Crow-Fukase syndrome, was responsible for the heart failure symptoms
      and left ventricular dysfunction in this patient.

PMID- 11518112
TI  - Discrepancy between inducibility of ventricular tachycardia and activity of
      cardiac sarcoidosis. Requirement of defibrillator implantation for the inactive
      stage of cardiac sarcoidosis.
AB  - Monomorphic ventricular tachycardia (VT) developed in two patients with cardiac
      sarcoidosis. Before treatment with prednisolone, technetium or gallium scintigram
      revealed abnormal accumulation in the heart and bilateral hilar lymph nodes, but
      programmed electrical stimulation failed to induce VT in either case.
      Prednisolone was administered and the abnormal accumulation of the scintigra ms
      disappeared. However, VT became reproducibly inducible, and in one of the
      patients, transient entrainment was demonstrated in clinical VT morphology.
      Defibrillators were implanted in both patients. Some VTs associated with cardiac
      sarcoidosis are due to reentry, and inducibility of VT is not associated with the
      activity of cardiac sarcoidosis. Even though steroid therapy suppresses the
      activity of cardiac sarcoidosis, defibrillator implantation is necessary to
      prevent a possible arrhythmic event during the follow-up.

PMID- 11518113
TI  - Diabetes mellitus associated with superior mesenteric artery syndrome: report of
      two cases.
AB  - We observed two patients with diabetes who were suffering from nausea, vomiting
      and epigastralgia after meals. These symptoms subsided when lying on their left
      side. Since the 2 patients had autonomic neuropathy, at first, the symptoms
      seemed to be attributable to diabetic gastroparesis. However, they were diagnosed
      as having superior mesenteric artery syndrome by hypotonic duodenography. These
      finding suggest that in diabetic patients who have a history of excessive weight
      loss superior mesenteric artery syndrome should be ruled out even though they
      have autonomic neuropathy.

PMID- 11518114
TI  - 46, XY pure gonadal dysgenesis: a case with Graves' disease and exceptionally
      tall stature.
AB  - A case of 46, XY pure gonadal dysgenesis with very tall stature was investigated.
      The 24-year-old, phenotypically female patient consulted our clinic because of
      linear growth persisting into adulthood. The patient was found to have no
      mutation or deletion of a sex-determining region of the Y chromosome, and also
      was found to have Graves' disease. Growth was arrested with height remaining at
      187 cm after normalization of the thyroid function by treatment with an
      antithyroid agent, although follow-up to monitor growth was limited to 3 months.
      In some cases of gonadal dysgenesis, then, Graves' disease may contribute to an
      abnormally tall stature.

PMID- 11518115
TI  - Painless thyroiditis induced by the cessation of betamethasone.
AB  - We describe the first reported case of painless thyroiditis induced by an abrupt
      cessation of betamethasone. A 53-year-old woman experienced transient
      thyrotoxicosis after the abrupt cessation of celestamine, a mixture of
      betamethasone and chlorpheniramine. Since neither TSH receptor- nor thyroid
      stimulating-antibodies were negative, and thyroid scintigram did not show the
      thyroid gland, she was diagnosed as having painless thyroiditis. Fourteen months
      after the onset of thyrotoxicosis, serum TSH was detectable without
      hypothyroidism. We speculate that reduction in betamethasone may be one of the
      triggers of painless thyroiditis.

PMID- 11518116
TI  - Pituitary apoplexy caused by luteinizing hormone-releasing hormone in prolactin
      producing adenoma.
AB  - We report a case in which pituitary apoplexy developed shortly after an
      intravenous (i.v.) injection of luteinizing hormone-releasing hormone (LH-RH). A
      56-year-old man with prolactin-producing pituitary tumor complained of severe
      headache, visual field loss and facial nerve palsy shortly after LH-RH test.
      Magnetic resonance image (MRI) revealed a hemorrhage in the pituitary adenoma. He
      showed dramatic improvement in his symptoms after decompression surgery. These
      findings suggest a causal relationship between the i.v. injection of LH-RH and
      pituitary apoplexy. Possible pituitary apoplexy should be kept in mind during
      pituitary testing.

PMID- 11518117
TI  - Regression of both pituitary and ovarian cysts after administration of thyroid
      hormone in a case of primary hypothyroidism.
AB  - We report a 19-year-old woman who was diagnosed as polycystic ovary.
      Hypothyroidism with a markedly elevated TSH level and an enlarged pituitary gland
      on MRI were noted. The 123I uptake was decreased to 6.5%. After treatment with
      thyroid hormone, regression of the enlarged pituitary and the ovarian cysts was
      observed. In the present case, hypothyroidism was considered to have caused a
      reversible enlargement of the pituitary gland and concomitant polycystic ovary.
      We concluded that the polycystic ovary might have resulted from the effects of an
      excessive amount of TSH on immature ovaries.

PMID- 11518118
TI  - Three Japanese patients from two families with generalized resistance to thyroid
      hormone with mutations in exon 9 of the thyroid hormone receptor beta gene.
AB  - Resistance to thyroid hormone (RTH) is a genetic disorder caused by mutations in
      the thyroid hormone receptor (TR) beta gene. The mutations are clustered in two
      regions: exon 9 and exon 10. To date, only one patient with an exon 9 mutation
      has been reported in Japan. We herein report three patients from two Japanese
      families with RTH and mutations in exon 9. A 52-year-old woman and her 18-year
      old daughter, both with inappropriate secretion of TSH (SITSH) were diagnosed
      simultaneously with generalized RTH. Molecular analysis revealed a G345D
      mutation. An 11-year-old girl with SITSH, whose only manifestation was a goiter,
      had an R338W mutation, which is frequently associated with pituitary RTH. Thus,
      RTH with mutations in exon 9 of the TR beta gene is not so rare in Japan.

PMID- 11518119
TI  - Hypoglycemia associated with the production of insulin-like growth factor II in
      adrenocortical carcinoma.
AB  - A 78-year-old woman was hospitalized for congestive heart failure and repeated
      hypoglycemic attacks. The laboratory data showed a serum insulin level within the
      normal range and an increased level of serum insulin-like growth factor (IGF) II.
      Abdominal ultrasonogram and computed tomography scan revealed a huge mass lying
      above the left kidney. She was diagnosed as having an adrenocortical carcinoma.
      After the removal of the tumor, the plasma glucose level and the serum level of
      IGF-II were normalized. The tumor cells stained positively for IGF-II
      immunohistochemically. These findings suggested that the hypoglycemia was due to
      IGF-II produced by the adrenocortical carcinoma.

PMID- 11518120
TI  - Pneumonitis induced by ou-gon (scullcap).
AB  - A 53-year-old Japanese man with recurrent interstitial pneumonia was referred to
      us. The patient had taken a traditional herb medicine, otsu-ji-to, before the
      onset of pneumonia. A provocation test for each herbal ingredient contained in
      otsu-ji-to revealed that the pneumonitis had been induced by ou-gon (scullcap).
      Lymphocytosis with the CD8+ T-cell subset predominance was found in the
      bronchoalveolar lavage fluid and lymphocytic alveolitis was noted in the
      transbronchial lung biopsy specimen after the provocation test. Ou-gon, or
      scullcap, should be included in the list of drugs with definite causal
      association with pneumonitis.

PMID- 11518121
TI  - Mammary involvement in a patient with sarcoidosis.
AB  - Sarcoidosis is a systemic granulomatous disease of unknown etiology. Sarcoidosis
      affects multiple organs; the lungs, lymphoid system, eyes and skin are usually
      involved. Commonly, any organ system may be affected. Sarcoid involvement in the
      nervous system, locomotor system, lacrimal and salivary glands, heart, kidney and
      liver has been recognized in patients with sarcoidosis. However, sarcoid
      involvement of the breast parenchyma has been extremely rare in patients with
      sarcoidosis. Herein, we report a patient with a sarcoid breast mass who had
      bilateral hilar lymphadenopathy and lymphocytosis in bronchoalveolar lavage
      analysis.

PMID- 11518122
TI  - Pulmonary epithelioid hemangioendothelioma coexistent with pulmonary metastasis
      of thyroid cancer.
AB  - We report a 45-year-old man with epithelioid hemangioendothelioma (EH) and
      simultaneous pulmonary metastasis of thyroid cancer in his lung. Thyroid cancer,
      and multiple small nodules in both lungs were noted. He underwent total
      thyroidectomy followed by radiotherapy with 131I. However, 131I scintigraphy
      showed poor uptake of radionuclide in the nodules, and the size of the nodules
      remained unchanged. The diagnostic thoracoscopic biopsy showed two types of
      nodules, some were positive for thyroglobulin and cytokeratin, and others were
      reactive for factor VIII. The former nodules were diagnosed as pulmonary
      metastases of thyroid cancer, and the latter EH.

PMID- 11518123
TI  - Disopyramide-induced pneumonitis, diagnosed by lymphocyte stimulation test using
      bronchoalveolar lavage fluid.
AB  - A 72-year-old man was admitted to our hospital with fever and cough. He had been
      on disopyramide treatment for nine days to control cardiac arrhythmia. On
      admission, chest X-ray examination revealed reticulonodular opacities in both
      lungs, and impending respiratory failure was evident. A differential cell count
      of the bronchoalveolar lavage fluid (BALF) showed a marked increase of
      lymphocytes. A lymphocyte stimulation test (LST) for disopyramide using BALF was
      positive, although the test using peripheral blood was negative. This case
      suggests that LST using BALF is useful for the diagnosis of drug-induced
      pneumonitis.

PMID- 11518124
TI  - Acute respiratory failure caused by vinorelbine tartrate in a patient with non
      small cell lung cancer.
AB  - We describe a case of vinorelbine tartrate (VNR) associated acute respiratory
      failure. A 65-year-old man with non-small cell lung cancer developed acute
      respiratory failure 50 minutes after his first infusion with VNR in combination
      with mitomycin-C. The patient was treated with furosemide, dopamine and high-dose
      methylprednisolone, and recovered with no discernible sequelae. Although clinical
      trials have shown that respiratory symptoms associated with VNR treatment have
      only rarely been observed and the putative mechanism remains to be elucidated,
      patients receiving VNR should be monitored carefully, particularly in the first
      few hours after intravenous administration.

PMID- 11518125
TI  - A rare case of eosinophilic pleuritis due to sparganosis.
AB  - A rare form of sparganosis with eosinophilic pleural effusion is reported. A 62
      year-old man was admitted to our hospital with left pleural effusion, and
      diagnosed immunologically as having sparganosis. Eosinophilia was seen in both
      peripheral blood and pleural effusion. The level of interleukin (IL)-5 was
      elevated in the pleural effusion, but not in peripheral blood. The patient was
      treated successfully with three consecutive doses of praziquantel (75 mg/
      kg/day). After the treatment, the antibody titer in serum decreased and the
      eosinophil number in the peripheral blood returned to the normal level. Thus,
      sparganosis should be included in the differential diagnosis for eosinophilic
      pleuritis. The immunoserological screening test using multiple-dot ELISA is
      helpful to identify the causative pathogen.

PMID- 11518126
TI  - Pulmonary lymphoma of large B-cell type mimicking Wegener's granulomatosis.
AB  - A 27-year-old man with a primary pulmonary lymphoma of large B-cell type is
      described. Symptoms involved both the upper and lower respiratory tract. A chest
      roentgenogram showed a dense mass with cavitation. Transbronchial biopsy
      specimens revealed no atypical cells, rather they demonstrated granulomatous
      infiltration and vasculitis consistent with but not conclusively diagnostic of
      Wegener's granulomatosis. The pulmonary mass became smaller after
      sulfamethoxazole-trimethoprim therapy. These features suggested Wegener's
      granulomatosis. However, an open biopsy specimen was diagnostic for diffuse
      lymphoma of large B-cell type. High-grade pulmonary lymphoma should be considered
      in the differential diagnosis of patients with clinical and pathologic features
      suggesting Wegener's granulomatosis.

PMID- 11518127
TI  - Acute interstitial pneumonia induced by ONO-1078 (pranlukast), a leukotriene
      receptor antagonist.
AB  - A 62-year-old woman treated with pranlukast for 2 months developed interstitial
      pneumonitis with a high fever. A lymphocyte stimulation test was reactive to
      pranlukast. Her clinical symptoms improved with discontinuation of pranlukast and
      administration of systemic corticosteroid. To our knowledge, this is the first
      reported case of drug-induced lung disease involving a leukotriene. The steps
      that can be taken to promptly reach a diagnosis and to successfully treat this
      life-threatening condition are described.

PMID- 11518128
TI  - Myelodysplasia associated with acquired immunodeficiency syndrome.
AB  - Two cases of acquired immunodeficiency syndrome with myelodysplasia are
      presented. Case 1 was admitted because of Pneumocystis carinii pneumonia. Mild
      anemia, thrombocytopenia and hypersegmented neutrophils were observed. After the
      administration of trimethoprim-sulfame-thoxazole and antiretroviral therapy,
      pancytopenia progressed. Bone marrow (BM) showed dysplastic hematopoiesis,
      suggesting human immunodeficiency virus-myelopathy. Case 2 was hospitalized due
      to progressive multifocal leukoencephalopathy. BM specimen obtained for
      thrombocytopenia showed myelodysplasia similar to myelodysplastic syndrome,
      suggesting that HIV may have an influence on hematopoietic progenitor cells.

PMID- 11518129
TI  - Successful therapy of pure red cell aplasia secondary to plasma cell dyscrasia
      with bolus methylprednisolone.
AB  - A 65-year-old man, who is a Jehovah's Witness, was admitted to our hospital due
      to progressive anemia following a four-year history of biclonal gammopathy of no
      clinical significance. He was diagnosed with pure red cell aplasia (PRCA)
      associated with plasma cell dyscrasia. Despite a markedly decreased red blood
      cell count (hematocrit 5.6%), the patient refused transfusion. He was
      intravenously administered bolus methylprednisolone. Reticulocytosis and recovery
      from anemia were observed on day 7 after the start of therapy. Secondary PRCA
      following plasma cell dyscrasia is a rare disorder; the treatments for this rare
      condition are discussed.

PMID- 11518130
TI  - Hypothalamic encephalitis with bradycardia.
AB  - A 74-year-old man developed fever, somnolence, hyponatremia, and life-threatening
      sinus bradycardia for three weeks. He showed a slight elevation of lymphocyte
      count and protein level in the cerebrospinal fluid. A brain CT scan revealed a
      diffuse low density area around the hypothalamus which was identified as a high
      intensity signal by flair MR imaging. Marked sinus bradycardia developed with no
      abnormality in the echocardiograph or cardiac enzymes. Over the next 6 weeks he
      became alert and normal sinus rhythm resumed. The results of endocrine tests were
      compatible with hypothalamic insufficiency with partial hypopituitarism and the
      syndrome of inappropriate secretion of ADH.

PMID- 11518131
TI  - Alternating paroxysmal hemiballism-hemichorea in bilateral internal carotid
      artery stenosis.
AB  - A 72-year-old man presented with paroxysmal and transient involuntary movements,
      or "limb shaking". The attacks occurred alternately from one side of the body to
      the other and ceased spontaneously. Surface EMG study showed synchronous grouping
      discharges in multiple limb muscles, being compatible with hemiballism
      hemichorea. Cerebral angiography demonstrated marked stenosis of the bilateral
      internal carotid arteries. Bilateral carotid endarterectomy led to complete
      disappearance of the involuntary movements. Alternating paroxysmal
      hemiballismhemichorea might be a transient ischemic attack, and alternating
      striatal dysfunction induced by cerebral hemodynamic or microembolic ischemia
      probably plays a central role in the occurrence of such involuntary movements.

PMID- 11518132
TI  - Periodic lateralized epileptiform discharges in influenza B-associated
      encephalopathy.
AB  - An 18-year-old woman presented with coma, hemicomvulsions, and transient periodic
      lateralized epileptiform discharges (PLEDs). Serological tests were positive for
      influenza B, and cerebrospinal fluid PCR for herpes simplex virus DNA was
      negative. Magnetic resonance imaging later showed abnormal signal intensity in
      the temporal lobe ipsilateral to the PLEDs. Influenza-associated encephalopathy
      may cause hemiconvulsions and PLEDs, and can mimic herpes simplex encephalitis.

PMID- 11518133
TI  - Shoulder stiffness: a common adverse effect of HMG-CoA reductase inhibitors in
      women?
AB  - Muscle symptoms are known as adverse effects of HMG-CoA reductase inhibitors but
      their incidence is reported to be low. We treated a case of shoulder stiffness
      related to such a drug, which prompted us to preliminarily survey its incidence.
      We found that nearly one-tenth of women (6/66) taking such drugs reported drug
      related shoulder stiffness. Shoulder stiffness is a very common symptom, while
      drug-induced shoulder stiffness is generally unknown. Many cases involving such
      an adverse effect may thus be overlooked. We present 2 typical cases here.

PMID- 11518134
TI  - Hodgkin's disease preceded by unique neurological symptoms.
AB  - This is the first case report of Hodgkin's disease (HD) which showed both
      remission and exacerbation of neurological signs before a confirmed diagnosis of
      HD. The episodes occurred three times and multiple lesions were involved.
      Immunoabsorption plasmapheresis and double filtration plasmapheresis were
      effective for the first episode, whereas, corticosteroids partly improved the
      second and third episodes. Fever and lymph node swelling were apparent afterward
      and she was diagnosed as having HD from a supraclavicular lymph node biopsy. The
      remaining neurologic deficits responded to chemotherapy and radiotherapy. The
      neurological symptoms were considered as a paraneoplastic syndrome of HD.

PMID- 11518135
TI  - Amyotrophic lateral sclerosis associated with sarcoidosis.
AB  - We report a rare association of amyotrophic lateral sclerosis (ALS) with
      incidental pulmonary and muscle sarcoidosis. A 63-year-old woman presented with
      slowly progressive weakness and atrophy of the extremities starting from the left
      leg. The biopsy of a small mass in the left gastrocnemius revealed a typical
      sarcoid nodule. She was treated with corticosteroid for possible sarcoid
      neuromyopathy. In spite of the treatment, her clinical course was relentlessly
      progressive and she died of bulbar palsy. Autopsy revealed a loss of motor
      neurons in the anterior horn, vacuolar degeneration of the lateral funiculus, and
      noncaseating granulomas in paratracheal lymph nodes and lungs. No granulomatous
      lesion or cellular infiltration was found in the spinal cord.

PMID- 11518136
TI  - Neurogenic pulmonary edema and large negative T waves associated with
      subarachnoid hemorrhage.
AB  - We describe a 72-year-old woman with hypertension who developed acute neurogenic
      pulmonary edema and giant negative T waves on electrocardiography (ECG) due to
      subarachnoid hemorrhage. The patient was alert and complained of precordial chest
      discomfort, dyspnea and shoulder stiffness. Echocardiography demonstrated normal
      left ventricle contraction with hypertrophy. Computed tomography (CT) and
      subsequent cerebral angiography revealed subarachnoid hemorrhage and saccular
      aneurysm at the anterior communicating artery. It is important to consider the
      possibility of subarachnoid hemorrhage when a patient shows pulmonary edema and
      ECG abnormalities even without typical clinical signs of subarachnoid hemorrhage.

PMID- 11518137
TI  - Rapid improvement of osteomalacia by treatment in a case with Sjogren's syndrome,
      rheumatoid arthritis and renal tubular acidosis type 1.
AB  - We present here a case of Sjogren's syndrome (SjS) with osteomalacia based on
      renal tubular acidosis type 1 (RTA-1). A 53-year-old woman, diagnosed as having
      rheumatoid arthritis (RA) at the age of 33, was admitted to our hospital because
      of sicca complex, fatigability and worsening general aching. The activity of RA
      had been low, but it was complicated by SjS, RTA-1 and remarkable osteomalacia.
      Acidosis was corrected by alkali supplement therapy. By treatment with a regimen
      consisting of alfacalcidol, calcium L-aspartate, elcatonin and ipriflavone, her
      bone mineral density (BMD) was remarkably improved within months and the
      generalized aching gradually diminished.

PMID- 11518138
TI  - An outbreak of allergy-like food poisoning.
AB  - Eight cases of allergy-like food poisoning resulting from the ingestion of
      yellowfin tuna, which had been kept in stock for 10 days prior to being cooked,
      are described. The main symptoms were headaches, facial flushing and palpitation.
      Samples of the ingested fish were analyzed for histamine content, and a high
      level of histamine was confirmed (310 mg/100 g of fish). Corticosteroids were
      given to 3 patients who exhibited dyspnea or persistent symptoms, while the
      remaining patients improved without medication. In situations where allergy-like
      clinical features are present after the ingestion of food, the possibility of
      allergy-like food poisoning should be recognized and included in a differential
      diagnosis.

PMID- 11518139
TI  - Herpes simplex virus bronchopneumonia in a non-immunocompromized individual.
AB  - We report a rare case of herpes simplex virus (HSV) bronchopneumonia in an
      otherwise healthy middle-aged individual. Bronchoscopy indicated scattered white
      coated lesions in the bronchial mucosa. The diagnosis was established following
      immunohistopathological staining for HSV of specimens obtained by bronchial
      biopsy. This case suggests that HSV could be a pathological agent of not only
      oral and genital mucosal lesions but also lower respiratory tract infection.

PMID- 11518140
TI  - Plasma mature form of adrenomedullin in diabetic nephropathy.

PMID- 11518141
TI  - Huge skin tumor diffuse large cell lymphoma associated with essential
      thrombocytosis.

PMID- 11518142
TI  - Modularity in musical processing: the automaticity of harmonic priming.
AB  - Three experiments investigated the modularity of harmonic expectations that are
      based on cultural schemata despite the availability of more predictive veridical
      information. Participants were presented with prime-target chord pairs and made
      an intonation judgment about each target. Schematic expectation was manipulated
      by the combination of prime and target, with some transitions being schematically
      more probable than others. Veridical information in the form of prime-target
      previews, local transition probabilities, or valid versus invalid previews was
      also provided. Processing was facilitated when a schematically probable target
      chord followed the prime. Furthermore, this effect was independent of all
      manipulations of veridical expectation. A solution to L. B. Meyer's (1967b) query
      "On Rehearing Music" is suggested, in which schematic knowledge contributes to
      harmonic expectation in a modular manner regardless of whether any veridical
      knowledge exists.

PMID- 11518143
TI  - Executive control of cognitive processes in task switching.
AB  - In 4 experiments, participants alternated between different tasks or performed
      the same task repeatedly. The tasks for 2 of the experiments required responding
      to geometric objects in terms of alternative classification rules, and the tasks
      for the other 2 experiments required solving arithmetic problems in terms of
      alternative numerical operations. Performance was measured as a function of
      whether the tasks were familiar or unfamiliar, the rules were simple or complex,
      and visual cues were present or absent about which tasks should be performed.
      Task alternation yielded switching-time costs that increased with rule complexity
      but decreased with task cuing. These factor effects were additive, supporting a
      model of executive control that has goal-shifting and rule-activation stages for
      task switching. It appears that rule activation takes more time for switching
      from familiar to unfamiliar tasks than for switching in the opposite direction.

PMID- 11518144
TI  - Inhibitory effects of repeating color and shape: inhibition of return or
      repetition blindness?
AB  - There is a current debate regarding whether attention is influenced by stimulus
      attributes other than location. The present article replicates and extends
      previous findings that repeating the nonspatial attribute of color leads to a
      delay in target detection (M. B. Law, J. Pratt, & R. A. Abrams, 1995). Repetition
      disadvantage effects were found for the stimulus attributes of both color and
      shape, as well as for location. However, the nonspatial repetition disadvantage
      disappeared if the stimuli were presented in peripheral locations (Experiments
      3a, 3b, and 4) or the cue was presented for 50 ms (Experiment 6). Moreover, the
      magnitude of the repetition disadvantage tended to decline as the cue-target
      stimulus-onset asynchrony increased (Experiments 5a, 5b, and 6). These results
      suggest that a repetition blindness mechanism may underlie the repetition
      disadvantage effects of nonspatial features, rather than an inhibition of return
      mechanism.

PMID- 11518145
TI  - Determinants of right-left and top-bottom prevalence for two-dimensional spatial
      compatibility.
AB  - When stimulus and response sets vary along horizontal and vertical dimensions,
      the horizontal dimension is more dominant than the vertical one, an effect called
      right-left prevalence. Three accounts have been proposed that attribute the
      effect to a reduced ability to code vertical locations when horizontal codes are
      also present, the use of right-left effectors, or a difference in salience of the
      2 dimensions. The accounts differ in terms of whether the ability to code and
      process the 2 dimensions is of limited capacity and whether the prevalence effect
      is a consequence of the effectors used for responding. The authors report 4
      experiments that evaluated these issues. Results indicate that use of right-left
      effectors is important to the right-left prevalence effect because it increases
      the salience of the horizontal dimension. However, a top-bottom prevalence effect
      can be obtained if the vertical dimension is made more salient.

PMID- 11518146
TI  - The role of perception in the mislocalization of the final position of a moving
      target.
AB  - The judged final position of a moving stimulus has been suggested to be shifted
      in the direction of motion because of mental extrapolation (representational
      momentum). However, a perceptual explanation is possible: The eyes overshoot the
      final position of the target, and because of a foveal bias, the judged position
      is shifted in the direction of motion. To test this hypothesis, the authors
      replicated previous studies, but instead of having participants indicate where
      the target vanished, the authors probed participants' perceptual focus by
      presenting probe stimuli close to the vanishing point. Identification of probes
      in the direction of target motion was more accurate immediately after target
      offset than it was with a delay. Another experiment demonstrated that judgments
      of the final position of a moving target are affected by whether the eyes
      maintain fixation or follow the target. The results are more consistent with a
      perceptual explanation than with a memory account.

PMID- 11518147
TI  - Attentional capture by irrelevant color singletons.
AB  - Four experiments investigated attentional capture by a color singleton in visual
      search for a nonsingleton target. B. S. Gibson and E. M. Kelsey (1998) found that
      a color singleton in a precuing array facilitated target discrimination at that
      location if the same color also signaled the target array onset. The authors
      found similar cuing effects regardless of whether the singleton color matched the
      target array and regardless of whether subjects could anticipate the singleton or
      target-array color. In Experiment 4, a color singleton captured attention when it
      appeared in the precuing array but not when it appeared in the target array. The
      results indicate that attentional control settings for displaywide attributes are
      imprecise: Although subjects may anticipate a specific color, they cannot avoid
      attentional capture by other irrelevant colors. In addition, the effect of
      irrelevant singletons depends on whether a target is simultaneously present in
      the array.

PMID- 11518148
TI  - Location of the egocenter in kinesthetic space.
AB  - The location of the egocenter in kinesthetic space was investigated in 4
      experiments. Participants, with their eyes closed, adjusted a comparison stimulus
      after or while touching a standard in a transverse plane at the belly or shoulder
      level so that they perceived the line joining the comparison and the fixed
      standard as pointing directly at themselves. The mean location of the
      intersections of the obtained lines was taken as the location of the egocenter.
      The main results showed that the location of the kinesthetic egocenter depended
      on the hand or hands used for touching, the timing of touching, and the distance
      of the standard from the participant. Implications of these results were
      discussed in relation to models of the kinesthetic egocenter.

PMID- 11518149
TI  - Is dual-task slowing instruction dependent?
AB  - When 2 tasks must be performed concurrently, each requiring a choice of response,
      dual-task slowing is typically found. However, E. H. Schumacher et al. (1997)
      reported that dual-task slowing can be eliminated when equal priority is assigned
      to each task. Experiment 1 largely confirmed this with the same tasks as
      Schumacher et al. (tasks using stimulus-response combinations of visual-manual
      and auditory-vocal pairings). Experiment 2 retained the equal-priority
      instructions but switched the task pairings (to visual-vocal and auditory
      manual); substantial dual-task slowing occurred. Experiment 3 used the same two
      response sets but only a single stimulus; slowing was again obtained despite
      equal priority instructions. Equalizing task priority was not sufficient to
      eliminate interference; relatively unusual cases in which dual-task interference
      is eliminated seem to depend on task-specific features.

PMID- 11518150
TI  - Temporal stimulus-response compatibility.
AB  - The study of element-level stimulus-response compatibility (SRC) has
      predominantly focused on spatial and symbolic relationships and has involved
      measures of response time and (dichotomous) error rate. This article explores a
      new form of SRC that is observed when duration is the relevant feature of both
      the stimulus and the response, using a more extensive analysis of performance
      accuracy and variability. The results indicate that element-level SRC generalizes
      to situations involving time as the relevant dimension of stimuli and responses.
      Evidence of this was found in all of the extracted measures of performance;
      however, temporal SRC was shown to have independent effects on when and how
      accurately a response was made. Implications for SRC research are discussed.

PMID- 11518151
TI  - Perceptual organization of moving stimuli modulates the flash-lag effect.
AB  - When a visual stimulus is flashed at a given location the moment a second moving
      stimulus arrives at the same location, observers report the flashed stimulus as
      spatially lagging behind the moving stimulus (the flash-lag effect). The authors
      investigated whether the global configuration (perceptual organization) of the
      moving stimulus influences the magnitude of the flash-lag effect. The results
      indicate that a flash presented near the leading portion of a moving stimulus
      lags significantly more than a flash presented near the trailing portion. This
      result also holds for objects consisting of several elements that group to form a
      unitary percept of an object in motion. The present study demonstrates a novel
      interaction between the global configuration of moving objects and the
      representation of their spatial position and may provide a new and useful tool
      for the study of perceptual organization.

PMID- 11518152
TI  - Asymmetric object substitution masking.
AB  - Object substitution masking occurs when a lateral mask persists beyond the
      duration of a target, reflecting reentrant processes in vision (V. Di Lollo, J.
      Enns, & R. Rensink, 2000). The authors studied whether substitution masking is
      location specific and whether it is symmetric around the target. A brief circular
      display of letters was presented along with a mask that designated the target.
      The mask was centered on the target or 1.1 degrees to the central or to the
      peripheral side. Substitution masking was found even when the target and the mask
      were at different locations. It was asymmetric and stronger when the mask was to
      the peripheral side of the target than to the central side. Asymmetric
      substitution was observed using various masks. It could not be explained by
      retina acuity gradients and was not attenuated by focused attention. The authors
      propose that target selection triggers an asymmetric inhibitory surround that is
      stronger toward the central side of the target.

PMID- 11518153
TI  - Learning to ignore the mask in texture segmentation tasks.
AB  - Although traditionally texture segmentation has been regarded as an automatic,
      preattentive process, participants confronted with texture segmentation in
      experimental settings (i.e., with brief presentation time and subsequent masking)
      are initially unable to perform the task. According to perceptual learning
      concepts, participants must learn to fine-tune their sensory channels before
      perception improves under restricted viewing conditions. The present article
      proposes an alternative perspective that emphasizes the role of the mask. Four
      experiments showed that the amount of observed learning depends on the structural
      and temporal homogeneity or heterogeneity of the mask. The authors suggest that
      learning consists of separating the task-relevant signal stemming from the
      texture from the task-irrelevant signal of the mask and of ignoring the mask.

PMID- 11518154
TI  - Redundancy gain in the stop-signal paradigm: implications for the locus of
      coactivation in simple reaction time.
AB  - The authors carried out 2 experiments designed to cast light on the locus of
      redundancy gain in simple visual reaction time by using a stop-signal paradigm.
      In Experiment 1, the authors found that single visual stimuli were more easily
      inhibited than double visual stimuli by an acoustic stop signal. This result is
      in keeping with the idea that redundancy gain occurs prior to the ballistic stage
      of the stop-signal task. In Experiment 2, the authors found that the response to
      an acoustic go signal was more easily inhibited by a double than by a single
      visual stop signal. This result provides conclusive evidence for a redundancy
      gain in the stop process--in a process that does not involve a motor response but
      rather its inhibition.

PMID- 11518155
TI  - Infant sensitivity to trajectory forms.
AB  - The authors investigated whether infants are sensitive to visual event trajectory
      forms, and whether they are sensitive to the underlying dynamics of trajectory
      forms. The authors habituated 8-month-old infants to a videotaped event run
      either forward or reversed in time and then switched them to the same event run
      in the opposite direction. Infants dishabituated when switched to the event with
      the novel direction in time, indicating sensitivity to the form of the
      trajectory. Infants exhibited equivalent habituation rates and looking times for
      forward and reversed events, thus failing to provide evidence that infants are
      sensitive to the underlying dynamics. In a partial replication of this first
      experiment, the same pattern of results was found. Both experiments revealed
      infant sensitivity to the trajectory forms, but not the underlying dynamics of
      events. The authors discuss implications for methods used in infant event
      perception studies.

PMID- 11518156
TI  - Steering toward a goal by equalizing taus.
AB  - Steering toward a target can be controlled by equalizing the time-to-closure of
      the angle between the target and the direction of locomotion and the time-to
      passage of the observer by the target. Two experiments required observers to
      steer through a computer-simulated environment toward a target depicted as either
      a floating cross that did not optically expand, a floating sphere that optically
      expanded or a grounded post that optically expanded. Experiment 1 revealed better
      performance in the post and sphere conditions, suggesting that steering is
      influenced by local optical expansion but not by perceived spatial target
      location or distance. Experiment 2 revealed differences in steering behavior
      between target types that suggested observers attempted to equalize time-to
      closure and time-to-passage.

PMID- 11518157
TI  - Attentional requirements is visual detection and identification: evidence from
      the attentional blink.
AB  - Perception of the 2nd of 2 targets (T1 and T2) is impaired if the lag between
      them is short (0-500 ms). The authors used this attentional blink (AB) to index
      attentional requirements in detection and identification tasks, with or without
      backward masking of T2, in 2 stimulus domains (line orientation, coherent
      motion). With masking, the AB occurred because T2 was masked during the
      attentional dwell time created by T1 processing (Experiments 1, 2, and 3).
      Without masking, an AB occurred only in identification because during the
      attentional dwell time, T2 decayed to a level that could support simple detection
      but not complex identification. However, an AB occurred also in detection if T2
      was sufficiently degraded (Experiment 4). The authors drew 2 major conclusions:
      (a) Attention is required in both identification and detection, and (b) 2 factors
      contribute to the AB, masking of T2 while attention is focused on T1 and decay of
      the T2 trace while unattended.

PMID- 11518158
TI  - Visual search for orientation among heterogeneous distractors: experimental
      results and implications for signal-detection theory models of search.
AB  - Three experiments tested a signal-detection theory (SDT) model of visual search
      (e.g., as described in J. Palmer, C. T. Ames, & D. T. Lindsey, 1993). In
      Experiment 1, participants searched for a 0 degrees line among distractors at (a)
      30 degrees; (b) 1/3 at 30 degrees, 2/3 at 50 degrees; (c) 1/3 at 30 degrees, 50
      degrees, and 70 degrees; and (d) 1/3 at 30 degrees, 2/3 at 70 degrees. The SDT
      model predicts improved performance in the more heterogeneous conditions, as some
      distractors are more discriminable from the target. In contrast, in Experiment 1
      human performance degraded in the more heterogeneous conditions (c and d). In
      Experiment 2, sparser displays improved the performance of the SDT model. In
      Experiment 3, search for theta degrees among homogeneous theta + 20 degrees
      distractors was compared with search for theta degrees among theta+/-20 degrees
      distractors. Performance in the latter condition was often worse, relative to
      performance in the homogeneous condition, than predicted by the SDT model;
      however, this depended greatly on the identity of the target.

PMID- 11518159
TI  - FDA warns against aminoglycoside residue in cattle.

PMID- 11518160
TI  - DEA addresses queries about Internet pharmacies.

PMID- 11518161
TI  - Understanding "usual and customary" charges.

PMID- 11518162
TI  - FDA finds more evidence of BSE compliance problems.

PMID- 11518163
TI  - Questions notion of enzymes in raw foods.

PMID- 11518164
TI  - More information on grape or raisin toxicosis.

PMID- 11518165
TI  - Comments on the outcome of stapled intestinal anastomoses.

PMID- 11518166
TI  - More information on rabid cat from Maryland.

PMID- 11518167
TI  - What is your diagnosis? Displacement of the maxillary canine teeth into the nasal
      cavity.

PMID- 11518168
TI  - Theriogenology question of the month. Laparotomy to assist replacement of the
      uterus.

PMID- 11518169
TI  - How anticipating relationships between dogs and children can help prevent
      disasters.

PMID- 11518170
TI  - 1999 income of US veterinarians.

PMID- 11518171
TI  - Risk factors and behaviors associated with separation anxiety in dogs.
AB  - OBJECTIVES: To determine potential risk factors and behaviors associated with
      separation anxiety and develop a practical index to help in the diagnosis of
      separation anxiety in dogs. DESIGN: Case-control study. ANIMALS: 200 dogs with
      separation anxiety and 200 control dogs with other behavior problems. PROCEDURES:
      Medical records were reviewed for signalment, history of behavior problems, home
      environment, management, potentially associated behaviors, and concurrent
      problems. RESULTS: Dogs from a home with a single adult human were approximately
      2.5 times as likely to have separation anxiety as dogs from multiple owner homes,
      and sexually intact dogs were a third as likely to have separation anxiety as
      neutered dogs. Several factors associated with hyperattachment to the owner were
      significantly associated with separation anxiety. Spoiling activities, sex of the
      dog, and the presence of other pets in the home were not associated with
      separation anxiety. CONCLUSIONS AND CLINICAL RELEVANCE: Results do not support
      the theory that early separation from the dam leads to future development of
      separation anxiety. Hyperattachment to the owner was significantly associated
      with separation anxiety; extreme following of the owner, departure cue anxiety,
      and excessive greeting may help clinicians distinguish between canine separation
      anxiety and other separation-related problems.

PMID- 11518172
TI  - Frequency of nonspecific clinical signs in dogs with separation anxiety,
      thunderstorm phobia, and noise phobia, alone or in combination.
AB  - OBJECTIVE: To determine the frequency of nonspecific clinical signs in dogs with
      separation anxiety, thunderstorm phobia, noise phobia, or any combination of
      these conditions and determine whether these conditions are associated in dogs.
      DESIGN: Case series. ANIMALS: 141 dogs. PROCEDURE: Diagnoses were established
      using specific criteria. Owners of dogs completed a questionnaire on how
      frequently their dogs exhibited destructive behavior, urination, defecation,
      vocalization, and salivation when the owners were absent and the types and
      frequency of reactions to thunderstorms, fireworks, and other noises. RESULTS:
      Associations of the 3 conditions and of various nonspecific clinical signs within
      and between diagnoses were nonrandom. The probability that a dog would have
      separation anxiety given that it had noise phobia was high (0.88) and
      approximately the same as the probability it would have separation anxiety given
      that it had thunderstorm phobia (0.86). However, the probability that a dog would
      have noise phobia given that it had separation anxiety (0.63) was higher than the
      probability that it would have thunderstorm phobia given that it had separation
      anxiety (0.52). The probability that a dog would have noise phobia given that it
      had thunderstorm phobia (0.90) was not equivalent to the converse (0.76).
      CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that dogs with any of these
      conditions should be screened for the others. Interactions among these conditions
      are important in the assessment and treatment of dogs with > 1 of these
      conditions. Responses to noise were different from those to thunderstorms,
      possibly because of the unpredictability and uncertainty of thunderstorms.

PMID- 11518173
TI  - Quality of tissue specimens obtained endoscopically from the duodenum of dogs and
      cats.
AB  - OBJECTIVE: To evaluate quality of duodenal tissue specimens obtained
      endoscopically from dogs and cats and submitted to 1 of 2 diagnostic laboratories
      for evaluation. DESIGN: Case series. SAMPLE POPULATION: Slides from 50
      consecutive canine and 50 consecutive feline endoscopically obtained duodenal
      tissue specimens submitted to laboratory 1 and 49 consecutive canine and 46
      consecutive feline specimens submitted to laboratory 2. PROCEDURE: Slides were
      examined independently by 3 investigators, and each tissue piece on each slide
      was classified as clearly inadequate, questionable, or clearly adequate on the
      basis of 4 criteria. An overall score was then assigned to the slide. RESULTS:
      Slides from laboratory 1 were more likely to be scored as clearly adequate and
      less likely to be scored as clearly inadequate than slides from laboratory 2.
      Clearly adequate slides from laboratory 1 had a higher number of clearly adequate
      pieces of tissue than did clearly adequate slides from laboratory 2. Slides
      scored as clearly adequate had a higher number of individual tissue pieces than
      did slides scored as clearly inadequate. CONCLUSIONS AND CLINICAL RELEVANCE:
      Results suggest that the quality of endoscopically obtained duodenal tissue
      specimens submitted to laboratories can vary, possibly because of differences in
      experience of individuals collecting biopsy specimens. Results suggest that at
      least 8 individual tissue pieces should be submitted when performing endoscopic
      biopsy of the duodenum in dogs and cats.

PMID- 11518174
TI  - Seroepidemiology of Bartonella vinsonii subsp berkhoffii exposure among healthy
      dogs.
AB  - OBJECTIVE: To determine seroprevalence of antibodies to Bartonella vinsonii subsp
      berkhoffii and risk factors for seropositivity among working dogs owned by the US
      government. DESIGN: Cross-sectional study. ANIMALS: 1,872 dogs. PROCEDURE: An
      ELISA was used to detect antibodies to B vinsonii subsp berkhoffii. RESULTS:
      Antibodies to B vinsonii subsp berkhoffii were detected in 162 dogs (8.7%; 95%
      confidence interval, 7.4 to 10.0%). Dogs living in the southeast, plains states,
      southwest, and south-central were significantly more likely to be seropositive
      than were dogs living in other regions of the United States. German Shepherd-type
      dogs were significantly less likely to be seropositive than were dogs of other
      breeds, and dogs entering training programs or that had been rejected from a
      training program were significantly more likely to be seropositive than were dogs
      used for narcotics detection and dogs trained to patrol or detect explosives.
      Dogs used by the border patrol or Federal Aviation Administration were more
      likely to be seropositive than were dogs used by the Department of Defense or
      customs service. Odds that dogs would be seropositive were significantly higher
      for dogs stationed in the southern United States, the northeastern United States,
      or a foreign country, compared with dogs stationed in all other regions of the
      United States. CONCLUSIONS AND CLINICAL RELEVANCE: Overall, 8.7% of this diverse
      group of healthy dogs was found to be seropositive for antibodies to B vinsonii
      subsp berkhoffii, and seropositivity rates were associated with location,
      suggesting either that there are multiple vectors for the organism or that the
      major vector for the organism depends on geographic and environmental factors.

PMID- 11518175
TI  - Survival times of and prognostic indicators for dogs with heart base masses: 25
      cases (1986-1999).
AB  - OBJECTIVE: To determine survival times of and prognostic indicators for dogs with
      heart base masses. DESIGN: Retrospective study. ANIMALS: 25 dogs. PROCEDURE:
      Medical records were reviewed to obtain information regarding signalment; initial
      complaint; results of physical examination, radiography, electrocardiography, and
      echocardiography; surgical findings; medical and surgical treatment; outcome;
      necropsy findings; survival time; and cause of death. RESULTS: Survival time
      ranged from 0 to 1,096 days (mean, 213 days; median, 57 days). None of the
      variables examined, including initial complaints and results of physical
      examination, radiography, electrocardiography, and echocardiography, were
      associated with survival time. However, dogs that underwent pericardectomy had a
      significantly longer mean survival time (mean +/- SD, 661 +/- 170 days) than did
      dogs that were treated medically (129 +/- 51 days). CONCLUSIONS AND CLINICAL
      RELEVANCE: Results suggest that dogs with heart base masses that undergo
      pericardectomy may survive longer than those that receive medical treatment
      alone.

PMID- 11518176
TI  - Plasma ionized calcium and parathyroid hormone concentrations in horses after
      endurance rides.
AB  - OBJECTIVE: To evaluate changes in plasma ionized calcium (Ca2+) and parathyroid
      hormone (PTH) concentrations in horses competing in endurance rides. DESIGN:
      Longitudinal clinical study. ANIMALS: 28 horses. PROCEDURE: Venous blood samples
      were obtained from horses before and after racing 80 km. Plasma pH and
      concentrations of Ca2+, PTH, inorganic phosphorus, albumin, lactate, and
      magnesium were measured. RESULTS: Overall, a significant decrease in mean (+/-
      SD) plasma Ca2+ concentration (from 6.44 +/- 0.42 to 5.64 +/- 0.42 mg/dl) and a
      significant increase in plasma PTH concentration (from 49.9 +/- 30.1 to 148.1 +/-
      183.0 pg/ml) were found after exercise. Exercise also resulted in significant
      increases in plasma inorganic phosphorus, albumin, and lactate concentrations. No
      changes in plasma magnesium concentration or pH were detected after exercise.
      Plasma PTH concentration was not increased after exercise in 8 horses; in these
      horses, plasma PTH concentration decreased from 58.2 +/- 26.3 to 27.4 +/- 22.4
      pg/ml, although plasma Ca2+ concentration was also decreased. CONCLUSIONS AND
      CLINICAL RELEVANCE: Plasma Ca2+ concentration was decreased after racing for 80
      km, compared with values obtained before racing. In most horses, an increase in
      plasma PTH concentration that was commensurate with the decrease in plasma Ca2+
      was detected; however, some horses had decreased plasma PTH concentrations.

PMID- 11518177
TI  - Aortic root disease in four horses.
AB  - Clinical findings in 4 horses with aortic root disease are described. Three of
      the horses had aneurysms of the right aortic sinus, and in 2 of the 3, the
      aneurysm ruptured, creating a fistula between the aorta and right ventricle. One
      of these horses had had a murmur since birth, and the aortic sinus aneurysm may
      have been a congenital anomaly. In a second horse, the aneurysm may have been an
      acquired condition that developed secondary to chronic aortic regurgitation.
      Another horse had a large subendocardial hematoma associated with dissection of
      blood from the aorta to the interventricular septum because of a tear in the
      aortic root near the right aortic sinus. Ventricular ectopy and signs of
      abdominal pain were the most common initial signs in these horses.

PMID- 11518178
TI  - Prevalence of antibodies against Mycobacterium avium subsp paratuberculosis among
      beef cow-calf herds.
AB  - OBJECTIVE: To estimate the prevalence of Mycobacterium avium subsp
      paratuberculosis infection among cows on beef operations in the United States.
      DESIGN: Cross-sectional seroprevalence study. Sample Population-A convenience
      sample of 380 herds in 21 states. PROCEDURES: Serum samples were obtained from
      10,371 cows and tested for antibodies to M avium subsp paratuberculosis with a
      commercial ELISA. Producers were interviewed to collect data on herd management
      practices. RESULTS: 30 (7.9%) herds had 1 or more animals for which results of
      the ELISA were positive; 40 (0.4%) of the individual cow samples yielded positive
      results. None of the herd management practices studied were found to be
      associated with whether any animals in the herd would be positive for antibodies
      to M avium subsp paratuberculosis. CONCLUSIONS AND CLINICAL RELEVANCE: Results
      suggest that the prevalence of antibodies to M avium subsp paratuberculosis among
      beef cows in the United States is low. Herds with seropositive animals were
      widely distributed geographically.

PMID- 11518179
TI  - Dietary energy density and weight regulation.
AB  - Dietary energy density (ED) has been suggested as an important determinant of
      energy intake and, therefore, energy regulation. This review summarizes published
      studies on the effects of dietary ED on hunger, satiety, energy intake, and body
      weight in healthy individuals, and compares the relative effects of ED
      manipulated by dietary fat only, fat and fiber, water, and type of sweetener. In
      short-term studies, consumption of low-ED foods promotes satiety, reduces hunger,
      and decreases energy intake with no marked differences between different dietary
      manipulations used to change ED. In addition, low-ED diets promote moderate
      weight loss in long-term studies. In studies lasting longer than 6 months, weight
      loss was more than three times as great in individuals consuming diets both low
      in fat and high in fiber compared with diets only low in fat (-3.4 kg versus -1.0
      kg). Combined, these studies suggest that diets low in fat and high in fiber may
      be the most effective low-ED diets for promoting weight loss. Further research is
      needed on the effects of dietary ED by changing water or sweetener content.

PMID- 11518180
TI  - Functional genomics and proteomics applied to the study of nutritional
      metabolism.
AB  - Functional genomics, commonly applied to the genes and enzymes involved in
      metabolism of chemicals, can also be applied to enzymes involved in the
      metabolism of nutrients. Although in its infancy, genomics can be used to
      determine relationships between nutrition and toxicology, drug metabolism, and
      cancer.

PMID- 11518181
TI  - Breastfeeding-related onset, flare, and relapse of rheumatoid arthritis.
AB  - The beneficial effects of pregnancy on rheumatoid arthritis have been known for
      decades. Only recently, however, have lactation and prolactin been targeted as
      predictors of onset, flare, or relapse of arthritis. Among genetically
      susceptible women, breastfeeding is associated with an increased risk of
      rheumatoid arthritis, particularly after the first pregnancy. Dietary
      interventions may reduce symptoms experienced by arthritic women.

PMID- 11518182
TI  - Iodine in human milk: perspectives for infant health.
AB  - Iodine is essential for normal growth, mental development, and survival of
      infants. The main source of iodine for breastfeeding infants is the iodine found
      in human milk. Despite the importance of iodine for infant health, there have
      been limited studies addressing human milk iodine concentrations. The newly
      recommended Adequate Intake of iodine for infants is 110 microg/day for infants 0
      6 months and 130 microg/day for infants 7-12 months. Further studies of human
      milk iodine are needed to ensure that iodine prophylaxis is providing sufficient
      iodine for mothers and infants worldwide.

PMID- 11518183
TI  - Sodium/hydrogen exchange and cardioprotection.

PMID- 11518184
TI  - Regulation of myocardial Na+/H+ exchanger activity.
AB  - The Na+/H+ exchanger is a plasma membrane protein, present in the myocardium,
      which removes intracellular protons and exchanges them with extracellular Na+.
      The protein comprises an N-terminal, hydrophobic, integral membrane domain that
      transports the ions and a C-terminal, hydrophilic region that regulates the N
      terminal domain. The C-terminal domain has several sub-domains, including one
      region that binds calmodulin and another that is phosphorylated by protein
      kinases. The Na+/H+ exchanger is activated by angiotensin, endothelin and alpha1
      adrenergic stimulation. These effectors increase phosphorylation of the C
      terminal domain by protein kinases, and G proteins have been implicated in this,
      but their role remains to be defined. It has recently been shown that ischemia
      and other stimuli lead to an increased expression of the Na+/H+ exchanger in the
      myocardium. The role of this increased expression in the pathology of ischemia
      and reperfusion-mediated myocardial damage has yet to be determined. Recent
      evidence suggests that the Na+/H+ exchanger may play a key role in hypertrophy of
      the myocardium, and that its activation through G protein-coupled receptors may
      be important in mediating its effects.

PMID- 11518185
TI  - Protection of the ischaemic myocardium by Na+/H+ exchange inhibitors: potential
      mechanisms of action.

PMID- 11518186
TI  - Sodium-hydrogen exchange inhibition: pre-versus post-ischemic treatment.
AB  - Sodium-hydrogen exchange is involved in ischemia-reperfusion injury. Despite the
      strong research support for the use of sodium-hydrogen exchange blockers to
      protect the myocardium during ischemia-reperfusion, there is still controversy
      regarding the most effective time for drug delivery. Studies that initiate drug
      treatment immediately before or at reperfusion have given conflicting results.
      The conflict in results may be due to differences in the experimental design.
      Post-ischemic cardioprotection may be less than optimal due to the vascular
      permeability barrier or a limited collateral circulation. Increasing the drug
      dose or allowing more time for the drug to cross the vessel wall may overcome
      this limitation. Determining the correct dose and delivery protocol, therefore,
      will be critical for the generation of positive results in future clinical trials
      and will optimize the beneficial effects of sodium-hydrogen exchange inhibition
      in the treatment of reperfusion injury.

PMID- 11518187
TI  - Do NHE inhibition and ischemic preconditioning convey cardioprotection through a
      common mechanism?

PMID- 11518188
TI  - Role of sodium-hydrogen exchange in cardiac hypertrophy and heart failure: a
      novel and promising therapeutic target.
AB  - The myocardial sodium-hydrogen exchanger (NHE), and more specifically the NHE-1
      isoform is now well-recognized to be a major contributor to ischemic and
      reperfusion injury. Recent evidence suggests that NHE-1 is also potential
      candidate for targeted intervention in terms of attenuation of the remodelling
      and hypertrophic processes which contributes to heart failure. Experimental
      studies have shown that NHE-1 inhibitors attenuate cardiomyocyte hypertrophy
      induced by various factors and reduce heart failure in vivo, independently of
      infarct size reduction. Although the precise cellular mechanisms for NHE-1
      involvement remain to be elucidated, current data suggest a potentially effective
      new therapeutic approach for the treatment of heart failure via NHE-1 inhibition.

PMID- 11518189
TI  - Delayed preconditioning of myocardium: current perspectives.
AB  - The protection conferred by ischemic preconditioning (PC) of myocardium occurs in
      a bimodal time course. The early cardioprotection wanes rapidly and is succeeded
      by a delayed phase of protection. This "second window" lasts for up to 72 hours,
      depending on species and end-point. A widely adopted paradigm for delayed PC is
      the following: 1) freely diffusible molecules or radicals, generated during the
      PC period, act in autocrine and/or paracrine manner as triggers of cellular
      adaptation; 2) they cause the activation of a protein kinase signal cascade; 3)
      the activated kinases phosphorylate important substrate proteins. In the case of
      delayed PC, it is thought that the phosphorylation of transcription factors,
      initiating the synthesis of late appearing effector proteins that promote cell
      survival during subsequent ischemia, may be a crucial event. Investigation of the
      proximal components of this sequence has altered our perceptions of several
      biological mediators, previously thought to be short acting, including adenosine,
      NO, free radicals and bradykinin. Signal transduction components include protein
      kinase C, tyrosine kinases and various mitogen- and stress-activated protein
      kinases but their patterns of regulation are complex and as yet poorly defined.
      Gene expression is modified in a regulated fashion to induce new proteins that
      promote cell repair and to protect against subsequent ischemia-reperfusion
      insult. It is likely that the complex nature of the preconditioning stimulus
      causes the activation of a variety of transcription factors, regulating a large
      number of target genes. So far, attention has focussed on a small number of
      protein products as potential distal mediators of delayed preconditioning. These
      include the heat shock proteins, manganese superoxide dismutase, inducible nitric
      oxide synthase, the ATP-sensitive potassium channel and cyclo-oxygenase-2.

PMID- 11518190
TI  - Monocyte chemoattractant protein-1 enhances and interleukin-10 suppresses the
      production of inflammatory cytokines in adult rat cardiomyocytes.
AB  - OBJECTIVE: Chemokines control the migration of leukocytes to inflamed tissue, and
      in particular monocyte chemoattractant protein (MCP)-1 has been implicated in the
      pathogenesis of several cardiovascular disorders such as chronic heart failure
      (CHF) and myocarditis. We hypothesised that MCP-1 may directly contribute to an
      inflammatory response in the cardiomyocytes, and in the present study we examined
      in adult rat cardiomyocytes: (i) the effect of tumour necrosis factor (TNF)alpha
      on MCP-1 production, (ii) the effect of MCP-1 on production of other inflammatory
      cytokines, and (iii) if the anti-inflammatory cytokine interleukin (IL)-10 could
      suppress any TNFalpha-induced MCP- 1 production. METHODS: We used enzyme
      immunoassays, RNase protection assays and slot blot analysis to measure protein
      and mRNA levels of various cytokines in adult rat cardiomyocyte cultures.
      RESULTS: (i) We found a approximately 6.4-fold increase of the MCP-1 level
      accompanied by an increase in MCP-1 mRNA accumulation in cardiomyocyte cultures
      after TNFalpha stimulation. (ii) In contrast, TNFalpha had no effect on IL-10 and
      only a modest effect on IL-1beta and IL-6 levels in these cells. (iii)
      Importantly, MCP-1 stimulated inflammatory response in cardiomyocytes by
      enhancing IL- 1beta and IL-6 levels in these cells as found at both the protein
      and mRNA level. (iv) Co-stim-ulation with IL-10 resulted in a approximately 55%
      reduction in TNFalpha-stimulated MCP-1 levels in cardiomyocyte culture
      supernatants. CONCLUSION: The present study demonstrates for the first time that
      MCP- 1 can directly affect cardiomyocytes, and we introduce MCP-1 as a potential
      enhancer and IL- 10 as a potential suppresser of inflammatory responses within
      the myocardium.

PMID- 11518191
TI  - Magnolol, a potent antioxidant from Magnolia officinalis, attenuates intimal
      thickening and MCP-1 expression after balloon injury of the aorta in cholesterol
      fed rabbits.
AB  - BACKGROUND: Restenosis is a common complication after balloon angioplasty. A
      number of cytokines, chemotactic factors and growth factors may be involved.
      Several antioxidants have been shown to inhibit intimal thickening after balloon
      injury in hyperlipidemic animals. OBJECTIVES: The effects of magnolol on the
      expression of monocyte chemotactic protein-1 (MCP-1) and intimal response in
      balloon injured aorta of cholesterol-fed rabbits were investigated. METHODS: Male
      New Zealand white rabbits were fed a 2% high cholesterol (HC) diet together with
      daily intramuscular injection of either 1 microg/kg B.W. of magnolol (HC-M, n =
      10) or vehicle (propylene glycol) as a control (HC-C, n = 10) for a total of 6
      weeks. Another 10 rabbits fed a regular diet also served as a control (C) group.
      A balloon denudation of abdominal aorta was performed in each group at the end of
      the third week. The aortas were harvested at the end of 6 weeks. RESULTS:
      Magnolol treatment significantly inhibited Cu2+-induced LDL oxidation in
      cholesterol-fed rabbits and reduced atheroma formation [atheroma area ratio: 0.10
      +/- 0.03 (HC-M) versus 0.33 +/- 0.07 (HC-C), p < 0.05] in thoracic aortas without
      lowering serum cholesterol. The intimal response was significantly attenuated in
      the HC-M rabbits when compared to those of the HC-C group [intimal thickness:
      88.95 +/- 14.91 microm (HC-M) versus 198.02 +/- 20.35 microm (HC-C), p < 0.05;
      intimal area: 278.21 +/- 43.16 x 10(3) microm2 (HC-M) versus 642.70 +/- 65.01 x
      10(3) microm2 (HC-C), p < 0.05]. The MCP-1 mRNA and protein expression were
      reduced in the HC-M group compared to the HC-C and C groups. CONCLUSION: The
      inhibitory effects on intimal hyperplasia and MCP-1 expression might be
      attributed to the antioxidant capacity of magnolol instead of lowering serum
      cholesterol. Magnolol may offer some protection against postangioplasty
      restenosis.

PMID- 11518192
TI  - Expression of GRK2 is increased in the left ventricles of cardiomyopathic
      hamsters.
AB  - Reduced beta-adrenergic responsiveness in the heart is a characteristic feature
      of heart failure. G protein-coupled receptor kinase 2 (GRK2) phosphorylates beta
      adrenoceptors in an agonist-dependent manner, causing receptor uncoupling and
      desensitisation. Elevated levels of both GRK2 mRNA and activity have been shown
      to occur in the failing human heart (Ungerer et al. (1992) Circulation 87: 454
      463). We have analysed levels of GRK2 protein in heart tissue from the
      cardiomyopathic Syrian hamster CHF 147 and compared these to GRK2 levels in age
      matched, non-cardiomyopathic control hamsters (CHF 148). GRK2 protein levels were
      found to be significantly increased in the left ventricles of the cardiomyopathic
      hamsters compared to the controls. The relative amounts of GRK2 in the
      cardiomyopathic hamsters, as compared to normal controls, increased with age from
      2-fold at 100 days to 5-fold at 350 days. These animals should provide a useful
      model for testing the effect of GRK2 inhibitors on the development of heart
      failure.

PMID- 11518193
TI  - Load-induced changes in repolarization: evidence from experimental and clinical
      data.
AB  - The high incidence of arrhythmias in patients with heart failure, hypertension,
      valvular heart disease, or mitral walve prolapse suggests a strong link between
      wall motion abnormalities and arrhythmias. A potential common mechanism
      underlying these observations may be that overload leads to electrophysiologic
      changes and facilitates arrhythmias. This article summarizes the interaction
      between changes in atrial and ventricular loading conditions and repolarization.
      Most experimental and clinical studies demonstrated 1) a reduction of action
      potential duration and refractoriness, 2) development of early
      afterdepolarizations, and 3) ectopic beats originating from these
      afterdepolarizations. Discrepancies between studies are related to different
      study designs, i.e., varying magnitude, velocity, and timing of increased load,
      the level of repolarization at which action potential duration is measured as
      well as different animal species. Direct effects of increased load on
      repolarization are most likely caused by activation of stretch-activated
      nonselective cation ion channels and changes in calcium handling. Current
      antiarrhythmic drug therapy is aimed at electrical disorders as the primary cause
      of arrhythmias. If mechanical disorders play a central role in the genesis of
      cardiac arrhythmias, future treatment should be directed at restoring a more
      normal mechanical function of the heart. Additional studies will further clarify
      the nature and clinical significance of load-related changes in repolarization
      and arrhythmogenesis.

PMID- 11518195
TI  - Beta-adrenergic receptors and intracellular signalling pathway in stunned and non
      ischemic regions of pig myocardium.
AB  - The beta-adrenergic pathway may have a role in the pathophysiology of ischemic
      syndromes characterised by reversible left ventricular dysfunction, such as
      myocardial stunning and other clinical conditions of unstable angina or coronary
      spasms, or chronic reversible left ventricular dysfunction, which might be a
      consequence of repeated events of short-term ischemia ("repetitive stunning"). A
      partial-to-total occlusion of the left anterior descending coronary artery in
      pigs was used to induce short periods of ischemia (total ischemic time 12 +/- 2
      min). Hypokinesis and dyskinesis of the myocardium were considered signs of
      myocardial dysfunction. We found a maintained function of the beta-adrenergic
      signalling system. Density and affinity of beta-adrenergic receptors were not
      different in stunned and non-ischemic regions, nor were cyclic AMP and cyclic GMP
      intracellular contents and ratio, nor well as the ratio of stimulatory/inhibitory
      G protein a subunits. Our findings are in agreement with a maintained beta
      adrenergic signalling system in the pathophysiology of chronic reversible left
      ventricular dysfunction.

PMID- 11518194
TI  - Extracellular matrix gene expression correlates to left ventricular mass index
      after surgical induction of left ventricular hypertrophy.
AB  - The cardiac extracellular matrix (ECM) is a dynamic entity maintaining the
      structural and functional properties of the myocardium. Little is known about
      alterations in ECM regulation during controlled induction of compensated left
      ventricular hypertrophy (LVH) using experimental aortic stenosis. Fifteen growing
      sheep received supra-coronary banding at an age of 7 +/- 1 months whereas 10 age
      matched sheep served as the control group (C). Explantation of the hearts was
      performed 8.3 +/- 1 months after banding. Gene sequences for sheep matrix
      metalloproteinase (MMP)-1,-2,-3,-9 and tissue inhibitors (TIMP)-1,-2,-3 were
      isolated and cloned. Then mRNA and protein gene expression analyses were
      performed. Concentric LVH with no evidence of heart failure was diagnosed at
      explantation. Left ventricular mass index (LVMI) was 150 +/- 33 g/m2 (LVH) versus
      88 +/- 23 (C) and 82 +/- 21 (baseline) (p < 0.01 versus LVH). Parallel to LVH
      there was a significant increase in mRNA and protein expression for MMP-1,-2,-3, 
      9 and for TIMP-1,-2 whereas there was a significant decrease in TIMP-3 gene
      expression. A close correlation between changes in LVMI and ECM gene expression
      was found. Compensated LVH goes along with a significant modification of MMP and
      TIMP gene expression. Alterations in ECM gene expression may be part of the
      adaptive process during left ventricular remodeling.

PMID- 11518196
TI  - Nitric oxide synthases in vagal neurons are crucial for the regulation of heart
      rate in awake dogs.
AB  - Nitric oxide synthase (NOS) inhibitors elicit bradycardias independent of the
      endothelium (e-NOS) or increases in blood pressure. Therefore, this bradycardia
      could be mediated by other NOS isoforms, most likely that of the nervous system
      (n-NOS). If so, heart rate variability (HRV) as a measure of vagal activity
      should be an indicator of the activity of n-NOS in vagal neurons. To test this,
      we studied the dose-effect relations of L-NAME (0.3 - 50 mg x kg(-1)) on heart
      rate (HR), HRV and systemic vascular resistance (SVR) in seven awake dogs. HRV
      was analyzed in the time domain as standard deviation of the RR-intervals (SDNN)
      and in the frequency domain as power in the high (0.15 - 0.5 Hz) and low (0.04 -
      0.15 Hz) frequency range. The effects of HR and SDNN reached their maxima at a
      dose of 3 mg x kg(-1) and had their ED50 at 0.27 +/- 0.03 mg x kg(-1) and 0.43 +/
      0.1 mg x kg(-1), respectively, whereas SVR had its maximum at 10 mg x kg(-1) and
      ED50 at 0.86 +/- 0.11 mg x kg(-1) (p < 0.05). HF-power (vagal activity)
      predominated compared to LF-power (mainly sympathetic activity) during baseline
      as well as after L-NAME. The effects on HR and HRV were absent after ganglionic
      blockade (hexamethonium), whereas the effects on SVR remained unchanged. Thus, NO
      exerts a powerful restraining activity on vagal neurons and plays a key role in
      the adjustment of heart rate in awake resting animals with prevailing vagal
      activity.

PMID- 11518197
TI  - Recording locations in multichannel magnetocardiography and body surface
      potential mapping sensitive for regional exercise-induced myocardial ischemia.
AB  - INTRODUCTION: This study aimed to identify the optimal locations in multichannel
      magnetocardiography (MCG) and body surface potential mapping (BSPM) to detect
      exercise-induced myocardial ischemia. METHODS: We studied 17 healthy controls and
      24 coronary artery disease (CAD) patients with stenosis in one of the main
      coronary artery branches: left anterior descending (LAD) in 11 patients, right
      (RCA) in 7 patients, and left circumflex (LCX) in 6 patients. MCG and BSPM
      signals were recorded during a supine bicycle stress test. The capability of a
      recording location to separate the groups was quantified by subtracting the mean
      signal amplitude of the normal group from that of the patient group during the ST
      segment and at the T-wave apex, and dividing the resulting amplitude difference
      by the corresponding standard deviation within all subjects. RESULTS: In MCG the
      optimal location for ST depression was at the right inferior grid for the RCA, at
      the mid-inferior grid for the LCX, and in the middle of these locations for the
      LAD subgroup (mean ST amplitudes: CAD -80 +/- 360fT, controls 610 +/- 660fT; p <
      0.001). In BSPM it was on the left upper anterior thorax for the LAD, left lower
      anterior thorax for the RCA, and on the lower back for the LCX subgroup (mean ST
      amplitudes: CAD -39 +/- 61 microV and controls 38 +/- 38 microV; p < 0.001). In
      MCG the optimal site for T-wave amplitude decrease was the same as the one for
      the ST depression. In BSPM it was on the middle front for the LAD, on the back
      for the LCX and on the left abdominal area for the RCA group. In accordance with
      electromagnetic theory, the largest ST segment and T-wave amplitude changes took
      place in MCG in locations orthogonal to those in BSPM. CONCLUSION: This study
      identified magnetocardiographic and BSPM recording locations which are sensitive
      for detecting transient myocardial ischemia by evaluation of the ST segment as
      well as the T-wave. These locations strongly depend on ischemic regions and are
      outside the conventional 12-lead ECG recording sites.

PMID- 11518198
TI  - Differential value of adenosine myocardial contrast echocardiography and
      dobutamine stress echocardiography in evaluating functional significance of
      coronary artery stenosis in a porcine model.
AB  - AIM: Myocardial contrast echocardiography (MCE) during adenosine induced
      hyperemia is an experimental method that detects flow limiting coronary artery
      stenosis by visualizing myocardial perfusion defects. Noninvasive detection of
      flow limiting coronary artery stenosis in clinical routine is a frequent domaine
      of dobutamine stress echocardiography (DSE) visualizing ischemia related regional
      wall motion abnormalities. This study investigated the values of adenosine MCE
      and DSE in the detection of functionally significant coronary artery stenosis in
      an experimental open chest pig model. METHODS: A total of 28 proximal LAD
      stenoses were instrumented in 12 animals. Reduction of coronary blood flow
      reserve (delta CFR [%] ) was calculated as a marker of functional significance of
      coronary artery stenosis (mild to moderate stenosis: delta CFR < or = 50%; severe
      stenosis: delta CFR > 50%). Fractional area shortening (FAS) and wall thickening
      (WT) were calculated to evaluate regional wall motion. Peak myocardial contrast
      intensities (PCI) were measured following aortic root injections of Levovist' to
      detect mocardial perfusion defects. RESULTS: As a group, severe stenosis
      significantly reduced wall motion response to dobutamine (delta FAS: 12.0 +/-
      3.0%, vs. 20 +/- 3.0% without stenosis, p < 0.05; delta WT: 2.2 +/- 0.9 mm vs.
      0.0 +/- 0.8 mm without stenosis, p < 0.05) and diminished myocardial
      opacification during hyperemia (PCI: 59 +/- 8 units vs. 143 +/- 16 units without
      stenosis, p < 0.05). Mild to moderate stenosis did not influence wall motion but
      reduced myocardial opacification (PCI 89 +/- 14 units vs. 143 +/- 16 units). PCI
      correlated more closely with alterations in CFR (r = -0.7, p < 0.0001) than did
      FAS (r = -0.5, p < 0.002) or WT (r = -0.2, p = 0.3). CONCLUSION: Adenosine
      myocardial contrast echocardiography detects flow limiting coronary artery
      stenosis and compares favorably to regional wall motion analysis during
      dobutamine infusion.

PMID- 11518199
TI  - Changes in time-trends of nutrient intake from fortified and non-fortified food
      in German children and adolescents--15 year results of the DONALD study. Dortmund
      Nutritional and Anthropometric Longitudinally Designed Study.
AB  - BACKGROUND: Although fortified products have played an increasing role in food
      marketing since the 1980s in Germany, data as to the consumption of fortified
      food is sparse. AIM OF THE STUDY: To assess long-term data on changes in
      fortified food supply or consumption patterns, nutrient intake, and time trends
      in the DONALD Study (Dortmund Nutritional and Anthropometric Longitudinally
      Designed Study). METHODS: Between 1985 and 2000 consumption of nutrient intake
      (total and from fortified foods) was evaluated and time trends in energy and
      nutrient intake were assessed on the basis of 3-day weighed dietary records (n =
      4193) of 2-14 year-old males (n = 383) and females (n = 404) enrolled in the
      DONALD Study. Nutrient intake was expressed as percentage of the current German
      recommendations. Food products were defined as fortified if enriched with at
      least one of the following nutrients: Vitamin A or provitamin A carotenoids
      (summarised as Vitamin A), Vitamins E, B1, B2, B6, C, niacin, folate, calcium or
      iron. Nutrient supplements and medicine were excluded from this evaluation. Time
      trends were analysed using linear and non-linear regression models (PROC MIXED,
      SAS 6.12). RESULTS: In percent of German references [3], non-fortified food
      contributed to folate intake by 20-30%, to Vitamin E by about 40%, to Vitamin B1
      by 50-65%, to Vitamin A, C, B2, calcium, iron by about 65-95%, and to Vitamin B6
      and niacin intake by 100% and more. Fortified food alone provided no more than 5%
      of calcium intake, about 10-20% of iron, Vitamin A and folate intake, up to 40
      50% of Vitamin C, B1, B2, E, niacin and up to 80% of Vitamin B6 intake. During
      the 15 year period of the DONALD Study with total food, we only found a
      significant linear time trend for Vitamin C, whereas significant non-linear time
      trends were found for calcium, Vitamin E, B1, B2, B6, niacin and folate. In the
      latter there was a uniform increase until 1994 and a decrease thereafter. For
      iron and Vitamin A no significant time trend could be identified. Only iron and
      Vitamin A intake from fortified food showed a significant linear time trend. All
      other nutrients studied here gave significant non-linear time trends. Nutrient
      intake with fortified food reached maximum values between 1994 and 1996 followed
      by a decrease thereafter. CONCLUSIONS: Signs of changing food consumption
      patterns were found, pointing to an almost uniform decrease of nutrient intake
      since 1994/96 in our population of German children and adolescents. This could be
      an alarming indicator of a slight but unpreferable tendency to eat energydense,
      nutrient-poor foods.

PMID- 11518200
TI  - Short-term fish oil supplementation improved innate immunity, but increased ex
      vivo oxidation of LDL in man--a pilot study.
AB  - BACKGROUND: Fish and fish oils are rich in the two long-chain polyunsaturated
      fatty acids (LCPUFAs) eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic
      acid (DHA, 22:6n-3). The n-3 LCPUFAs have been reported to have beneficial
      effects on cardiovascular functions, but their role in relation to immune
      functions is still controversial. AIM OF THE STUDY: The objectives of this study
      were to determine the effects of supplementation with fish oil on immune cell
      functions in human subjects. We have also assessed the effects on plasma lipids,
      antioxidant status and susceptibility of low-density lipoproteins (LDL) to
      oxidative stress. The antioxidant status was determined by measuring plasma
      vitamin C, tocopherols and carotenoids in plasma and LDL, and superoxide
      dismutase (SOD) in red blood cells. DESIGN: For 30 days, 10 volunteers ingested
      25 g/d of either fish oil, providing n-3 LCPUFAs (7.5 g), or high-oleic sunflower
      oil, providing monounsaturated fatty acids mainly as oleic acid (22 g). The oils
      contained similar profiles of tocopherols. At day 0 and day 30, blood samples
      were drawn by venipuncture for plasma lipid and antioxidant analyses and
      lipoprotein isolation, and for isolation and functional tests of mononuclear
      cells and granulocytes. Fatty acid profiles of im mune cells and LDL were also
      determined. RESULTS: Fish oil supplementation resulted in an accumulation of n-3
      LCPUFAs (EPA, DHA) in LDL and immune cells. The phagocytic activity, a measure of
      immune cell activity, was increased in both groups. Whereas the plasma and LDL
      antioxidant status do not appear to be affected by fish oil supplementation, an
      increased susceptibility of LDL to oxidation was observed in these healthy
      volunteers. CONCLUSIONS: The optimal amounts of n-3 fatty acids required to
      modulate immune functions remain to be established. In addition, adequate levels
      of antioxidant protection need to be provided during fish oil supplementation.

PMID- 11518201
TI  - Cholesterol-lowering effect of spreads enriched with microcrystalline plant
      sterols in hypercholesterolemic subjects.
AB  - BACKGROUND: Plant sterols have been shown to reduce serum lipid concentrations.
      The effectiveness is highly dependent on the physical state of the plant sterols.
      By means of a new crystallizing method, plant sterols can be added into dietary
      fats and oils homogeneously. In this fat ingredient, plant sterols are in a
      microcrystalline form. AIMS OF THE STUDY: We investigated the cholesterol
      lowering effect and possible side effects of vegetable oil-based spreads
      fortified with two different doses of microcrystalline plant sterols. METHODS:
      This double-blind randomized, placebo-controlled study consisted of a 6-wk run-in
      and a 6-month experimental period. During the run-in period, all 155
      hypercholesterolemic subjects received rapeseed oil-based control spread. In the
      beginning of the experimental period subjects were randomly assigned into one of
      three experimental groups. The control group continued to use control spread, and
      the two test groups used spreads with added plant sterols of either 1.5 g/d or
      3.0 g/d. The subjects consumed test spreads as a part of their normal diet
      without any restrictions in lifestyle and diet. RESULTS: Plasma total- and LDL
      cholesterol concentrations were significantly reduced by 7.5-11.6% (0.46-0.62
      mmol/1) in groups consuming margarine enriched with free plant sterols, compared
      with the control group. The effects were similar between the two groups consuming
      either 1.5g or 3.0 g plant sterols per day. No effect on HDL-cholesterol or
      triacylglycerol concentrations occurred. The test spreads did not induce any
      adverse effects in blood clinical chemistry, hematology or decreases in serum
      concentrations of lipid soluble vitamins. CONCLUSIONS: Microcrystalline plant
      sterols are effective in lowering serum total- and LDL-cholesterol concentrations
      without obvious side effects. The daily dose of 1.5 g plant sterols is enough to
      reach the maximum effect.

PMID- 11518202
TI  - Antioxidant and radical scavenging properties in vitro of polyphenolic extracts
      from red wine.
AB  - BACKGROUND & AIMS: Red wine polyphenols inhibit chemically-induced oxidative DNA
      damage in vivo in experimental animals through a mechanism which is still
      unclear. On this basis, we tried to clarify the mechanisms of inhibition of DNA
      oxidation in vitro by wine extracts containing monomeric and polymeric phenols
      (WE) and monomer-free complex polyphenols and tannins (WCPT) from red wine.
      METHODS: Oxidative DNA damage was induced by incubating DNA with GSH/Fe3+ or
      cumene hydroperoxide (CumOOH) in vitro and using 8-OH-2-deoxyguanosine (8-OHdG)
      levels as a measure of DNA oxidation. Levels of 8-OHdG were determined by HPLC
      coupled with electrochemical detector (ESA). RESULTS AND CONCLUSIONS: WCPT and
      WE, at microM concentrations, reduced concentration-dependently oxidative DNA
      damage induced by GSH/Fe3+. WCPT and WE also reduced DNA oxidation by CumOOH. In
      conclusion, complex polyphenols and tannin extracts from red wine, with or
      without small molecular phenols, prevent oxidative DNA damage through a dual
      mechanism, iron binding and direct free radical scavenging.

PMID- 11518203
TI  - Relationship between dietary intake, antioxidant status and smoking habits in
      female Austrian smokers.
AB  - BACKGROUND: Previous studies have shown that cigarette smoke contains many
      oxidants and free radicals, which can increase lipid peroxidation. AIM OF THE
      STUDY: The association between smoking, food pattern, especially vitamin intake
      and plasma concentrations of important antioxidants, as well as lipid
      peroxidation products was assessed in this cross-sectional study. SUBJECTS AND
      METHODS: Sixty Austrian women aged 18-40 y were enrolled in the study. Twenty
      nine women were allocated to the smoking group; thirty-one women served as
      nonsmoking controls. Plasma concentrations of alpha- and gamma-tocopherol, alpha-
      and beta-carotene, lycopene, cryptoxanthin, retinol, ascorbate and
      malondialdehyde were determined by HPLC; dietary intake and food pattern had been
      assessed by four 24-h dietary intake recalls and one food frequency
      questionnaire. RESULTS: Generally, food intake patterns were not different
      between smoking and nonsmoking women. But, a significantly higher intake of
      alcohol was observed in the smoking group (P < 0.05). Plasma ascorbic acid
      concentration of the smoking group did not differ from the nonsmoking women.
      Despite the increased utilization because of the oxidative stress in smokers,
      this result might be explained by the high dietary intake of vitamin C in our
      smoking group. Significantly lower plasma concentrations of alpha-,beta-carotene
      and lycopene have been partly ascribed to the enhanced metabolic turnover
      resulting from smoking-induced oxidative stress. Our results confirm that smoking
      had no effects on plasma tocopherol and plasma retinol concentrations.
      CONCLUSIONS: The poor supply with the carotenoids alpha-, beta-carotene and
      lycopene may result from the increased metabolism of antioxidants caused by
      oxidative stress and may be responsible for significantly higher levels of lipid
      peroxidation products in smokers compared to nonsmokers (P < 0.05).

PMID- 11518205
TI  - Interaction of swine nursery and grow-finish space allocations on performance.
AB  - Two experiments were conducted to evaluate the possible interaction of nursery
      space allocations and grow-finish space allocations in swine. In Exp. 1, crowding
      was achieved by varying the number of pigs per pen. During the nursery phase,
      decreasing the space allocation (0.16 m2/pig vs 0.25 m2/pig; 8 and 12 pens per
      treatment, respectively) by increasing the number of pigs per pen (18 vs 12)
      resulted in a decrease in daily feed intake (0.609 vs 0.683 kg/d; P < 0.001) and
      daily gain (0.364 vs 0.408 kg/d; P < 0.001). Pigs were mixed within nursery
      treatment groups and reassigned to grow-finish pens (6 pens per treatment) at the
      end of the 35-d nursery period providing either 0.56 m2/pig (14 pigs/pen) or 0.78
      m2/pig (10 pigs/pen). Crowding during the grow-finish phase decreased daily feed
      intake (P < 0.003) and daily gain (P < 0.001). In Exp. 2, space allocations of
      0.16 m2/pig vs 0.23 m2/pig during the nursery phase (24 pens per treatment)
      resulted in a decrease in daily feed intake (0.612 vs 0.654 kg/d; P < 0.005) and
      daily gain (0.403 vs 0.430 kg/d; P < 0.001). Pigs remained in the same (social)
      groups when moved to the grow-finish phase. Unlike Exp. 1, there was no effect of
      crowding during the grow-finish phase (0.60 m2/pig vs 0. 74 m2/pig) on daily feed
      intake or daily gain. The difference in results between experiments suggests that
      the response to crowding during the grow-finish phase may depend in part on
      whether pigs are mixed and sorted following movement from the nursery.

PMID- 11518204
TI  - Evaluation of polyphenol bioavailability in rat small intestine.
AB  - BACKGROUND: Dietary polyphenols, which are contained in several foods of plant
      origin, have been reported to be effective protective agents against
      cardiovascular diseases and cancer. However, data on their absorption from the
      gastrointestinal tract are still scarce and, often, contradictory. AIM OF THE
      STUDY: In this report, evaluation of polyphenol bioavailability was carried out
      by using segments of the small intestine from rat. The extent of absorption
      throughout the small intestine of rat was evaluated with two model compounds,
      tannic acid and catechin, as representatives of high and low molecular weight
      polyphenols, respectively. The consequence of the binding of tannic acid to BSA
      on both tannic acid absorption and in vivo protein digestibility was also
      examined. METHODS: Polyphenol solutions of different concentrations were injected
      into the lumen of ligated segments (6 cm) of the small intestine and the segments
      incubated in buffer for 5 min. The residual amount of polyphenol in the lumen of
      each segment was assayed by maximum absorption in the UV/VIS optical spectrum as
      was the amount of compound that had crossed the gut wall into the incubation
      buffer. Digestibility of BSA and of a BSA- tannic acid complex was assayed with
      rats. RESULTS: The results indicated a significant, concentration-dependent,
      disappearance of both polyphenols from the small intestine of the rat, with
      higher uptake levels being evident for tannic acid (50%) than catechin (30%).
      However, complete transfer through the gut wall was not observed with tannic acid
      whilst low but significant amounts (10%) were detected in incubation buffers with
      catechin. Partial binding of polyphenols by endogenous proteins in the intestinal
      lumen was also demonstrated. Complexing tannic acid with BSA (1:10 mol/mol) was
      not found to affect either the extent of interaction of tannic acid with the
      small intestine or the in vivo digestibility of the protein. CONCLUSIONS: Our
      experiments show that tannic acid and catechin both interact with the gut but
      only catechin appears able to traverse the gut. In addition, they provide
      evidence for binding of tannic acid and catechin by endogenous proteins in the
      intestinal lumen. This may limit their absorption from the small intestine. BSA
      complexed with tannic acid was as readily digested as BSA alone. This may suggest
      that tannic acid exerts anti-nutritional effects by binding to proteins of the
      gut wall and interfering with gut function rather than by inhibition of dietary
      protein digestion.

PMID- 11518206
TI  - The effect of litter size before weaning on subsequent body development, feed
      intake, and reproductive performance of young rabbit does.
AB  - An experiment was performed to study the effect of litter size before weaning on
      subsequent body development and composition, feed intake, and reproductive
      performance of young rabbit does with the objective to improve reproductive
      performance. Litter size (LS) before weaning (treatment) was 6, 9, or 12 kits.
      After weaning (30 d), 58 female kits per treatment (in two successive replicates)
      were reared and fed for ad libitum intake to 14.5 wk of age (end of rearing). At
      14.5 wk of age, receptive does were inseminated. Nonreceptive and nonpregnant
      does were inseminated at 17.5 wk of age. The experiment ended when the second
      litter was weaned. Part of the animals was slaughtered to determine body
      composition at the end of the experiment (replicate one) and at the end of
      rearing (replicate two). At weaning, BW differed among treatments (P < 0.05; 855,
      773, and 664 +/- 15 g for LS6, 9, and 12, respectively). Compensatory growth was
      observed. At the end of rearing, LS12 does were smaller (P < 0.05) than LS9 and
      LS6 does (3,524, 3,778, and 3,850 +/- 48 g, respectively). After first lactation,
      no difference in BW among treatments was found. Compared with LS6, empty body
      weight (BW minus gut, bladder, and uterus content) of LS12 contained more (P <
      0.05) nitrogen (32.5 vs 31.1 +/- 0.3 g/kg), more (P < 0.05) ash (30.7 vs 28.3 +/-
      0.6 g/kg), and less (P < 0.05) fat (168.6 vs 200.2 +/- 8.6 g/kg). No differences
      in body composition among treatments were found at the end of the experiment.
      During rearing, LS12 had the lowest (P < 0.05) daily feed intake (152, 164, and
      169 +/- 2 g/d for LS12, 9, and 6, respectively). During the reproductive period,
      no differences in feed intake among treatments were found. Kindling rate (the
      number of kindlings per number of inseminations) was not influenced by treatment.
      In the first parity, total litter size (number of alive and stillborn kits) was
      lower (P < 0.10) for LS12 than for LS9 (6.4 vs 8.6 +/- 0.5, respectively). When
      first mating was delayed by 3 wk, an increased (P < 0.05) total litter size was
      found regardless of treatment (7.5 and 9.4 +/- 0.3 for 14.5, and 17.5 wk,
      respectively). Decreasing litter size before weaning from nine to six kits did
      not alter future reproductive performance. Based on results of this study, it
      seems advisable to perform a limited standardization level (at nine kits) after
      kindling and postpone first mating to an older age (17.5 wk) to improve
      reproductive performance.

PMID- 11518207
TI  - Predicting individual feed requirements of cattle fed in groups.
AB  - A published model designed to predict individual feed required for the observed
      shrunk BW and ADG of growing cattle when fed in groups was modified and evaluated
      to improve its accuracy. This model is needed to accurately bill feed and compute
      cost of gain in marketing programs based on individual animal management. Because
      of its importance in predicting energy required for growth, a database of 401
      steers was used to develop an equation to predict percentage of empty-body fat
      (EBF) from carcass measurements (12th rib fat thickness, hot carcass weight, USDA
      quality grade, and longissimus muscle area), which accounted for 61% of the
      variation in EBF with no bias (P > 0.1). When tested with an independent data set
      of 951 steers, the equation accounted for 51% of the variation with 1%
      proportional bias. The large variation in the carcass measurements at a
      particular EBF observed in this study indicates further improvement is limited by
      the inability of carcass measurements to account for variation in fat
      distribution in the various carcass components. Because of its importance in
      setting the target end point, a database of 1,355 steers and heifers was used to
      determine the relationship between EBF and USDA quality grade. These data
      indicate growing and finishing cattle reach Select and low-Choice quality grades
      at an EBF of 26.15 +/- 0.19 and 28.61 +/- 0.20%, respectively (P < 0.05). A data
      set of 228 steers from different breeds from two serial slaughter studies
      indicated 14.26 +/- 1.52 kg of empty BW change are required to increase EBF one
      percentage unit for cattle fed high-energy diets; this adjustment is needed to
      adjust final shrunk BW to the target EBF end point. The model to predict DM
      required with modifications developed in this study was evaluated with data from
      365 individually fed cattle and it accounted for 74% of the variation in observed
      DM consumed with no bias (P > 0.1). When the revised model was applied to a
      commercial feedlot data set containing 12,105 steers and heifers, the total
      observed DM consumed was predicted with a bias of less than 1%. The model
      presented in this study accounts for differences known to affect animal
      requirements (breed type, BW and ADG, and weight at the target EBF end point) and
      can be used to fairly allocate feed to individuals fed in a group under
      commercial feedlot conditions.

PMID- 11518208
TI  - Incidence of mastitis in beef cows after intramuscular administration of
      oxytetracycline.
AB  - There is limited information on the value of antibiotic therapy for mastitis in
      beef cows. Effects of antibiotic treatment at weaning and the subsequent calving
      on calf weaning weight, milk somatic cell counts, milk components, and
      intramammary infection were studied in beef cows. Additionally, effects of number
      of infected mammary quarters, number of dry mammary quarters, type of
      intramammary pathogen, and parity on response variables were determined. Cows (n
      = 192) were randomly assigned to treatments in a 2 x 2 factorial arrangement;
      factors were time of treatment (weaning and after calving) and treatment (vehicle
      and vehicle plus antibiotic). Oxytetracycline (LA-200) or vehicle was
      administered intramuscularly following collection of quarter milk samples at
      weaning and calving. Percentage of infected cows and quarters averaged 43.4 and
      16.4%, respectively, at calving and increased (P < 0.05) to 53.7 and 29.7% at
      weaning. Calves from cows with one or two dry quarters weighed 12.7 kg less (P <
      0.05) at 90 d after calving and 18.7% less (P < 0.05) at 212 d after calving than
      calves from cows with no dry quarters. Calves from cows with three or four
      infected quarters weighed 17.5 kg less (P < 0.05) at 90 d and 25.5 kg less (P <
      0.05) at weaning than calves from cows with two or fewer infected quarters.
      Infections by Staphylococcus aureus and coagulase-negative staphylococci were the
      most common and accounted for 67 and 78% of the infections. Percentages of
      infected cows and quarters, infections caused by S. aureus, and dry quarters
      increased (P < 0.05) with parity. No differences were found among antibiotic
      treatments for any of the response variables studied. Intramuscular
      oxytetracycline was not effective in the control of mastitis in beef cows under
      the conditions of the study.

PMID- 11518209
TI  - Growth, puberty, and carcass characteristics of Brahman-, Senepol-, and Tuli
      sired F1 Angus bulls.
AB  - Postweaning growth, sexual development, libido, and carcass data were collected
      from two consecutive calf crops using 31 Brahman x Angus (B x A), 41 Senepol x
      Angus (S x A), and 38 Tuli x Angus (T x A) F1 bulls. Following weaning (by mid
      September) and preconditioning, at the start of the study (late September) bulls
      were fed concentrate (three times each week at a rate equivalent to 4.5 kg/d) on
      bahiagrass pasture for approximately 250 d. At the start of the study and at 28-d
      intervals, BW, hip height, and scrotal circumference (SC) were measured.
      Concurrently at 28-d intervals, when the SC of a bull was > or = 23 cm, semen
      collection was attempted using electroejaculation. Ejaculates were evaluated for
      presence of first spermatozoa (FS), 50 x 10(6) sperm with at least 10% motility
      (PU), and 500 x 10(6) sperm with at least 50% motility (PP). After all bulls
      reached PP they were subjected to two libido tests. Carcass data were collected
      on all bulls (n = 110) and Warner-Bratzler shear (WBS) force values were assessed
      on a subset (n = 80). For both years, B x A bulls were heavier (P < 0.05) and
      taller (P < 0.05) than S x A and T x A bulls at the start and end of the study.
      However, breed type did not influence (P > 0.10) gain in BW or hip height during
      the study. Scrotal circumference of T x A bulls was larger (P < 0.05) than that
      of B x A or S x A bulls at the start of the study, but there was no effect (P >
      0.10) of breed type by the end of the study. At PU and PP, B x A bulls were older
      (P < 0.05), heavier (P < 0.05), and taller (P < 0.05) and had larger (P < 0.05)
      SC than S x A and T x A bulls. Tuli x Angus bulls were younger (P < 0.05) than S
      x A bulls at PU and PP but had similar SC. Libido scores tended (P < 0.10) to be
      lower for B x A than for S x A and T x A bulls. Breed type affected (P < 0.05)
      carcass traits; B x A bulls had the heaviest (P < 0.05) hot carcass weight,
      greatest (P < 0.05) dressing percentage, larger (P < 0.05) longissimus muscle
      area than S x A bulls, and higher (P < 0.05) USDA yield grade than T x A bulls
      but greatest (P < 0.05) WBS force values. Breed type did not affect (P > 0.10)
      USDA quality grade. In conclusion, tropically adapted F1 bulls produced from
      Senepol (Bos taurus) and Tuli (Sanga) sires bred to Angus cows in Florida had
      lighter BW, shorter hip heights, and smaller carcasses than those from Brahman
      sires but reached puberty earlier and had higher libido scores and lower WBS
      force values.

PMID- 11518210
TI  - Optimum mating systems for the myostatin locus in cattle.
AB  - Inactive myostatin (one or two copies) results in increased muscularity,
      increased yield of closely trimmed retail product, reduced fat content, increased
      lean growth efficiency, reduced quality grade, increased birth weight, and
      increased dystocia. Even though one or two copies of inactive myostatin reduces
      quality grade or marbling compared to zero copies, there is no decrease in meat
      tenderness. It may be possible to use mating systems to make the most of the
      advantages of inactive myostatin while minimizing the disadvantages. The
      objective of this study was to develop a method to compare mating systems among
      genotypes at the myostatin locus. Economic variables that influence the
      profitability of alternative mating systems are prices per unit of retail product
      for USDA quality grades Standard, Select, and Choice; cost of an assisted
      calving; and cost of genotyping. Because of variation in both economic variables
      and biological parameters, a single mating system is not expected to universally
      maximize profit. We identified seven mating systems that each yield maximum
      profit for different combinations of values for biological parameters and
      economic variables. Use of inactive myostatin was profitable as long as the price
      for Select was at least 80% of the Choice price and the price for Standard at
      least 60%. As the price for Select and Standard increase up to the Choice price,
      mating systems that produce a higher proportion of inactive myostatin alleles
      become more profitable. Profitable use of inactive myostatin depends either on
      retaining ownership of beef until it is fabricated into retail product or the
      development of specialty markets that place greater value on lean yield and less
      on marbling, unlike conventional U. S. markets.

PMID- 11518211
TI  - The Bayesian controversy in animal breeding.
AB  - Frequentist and Bayesian approaches to scientific inference in animal breeding
      are discussed. Routine methods in animal breeding (selection index, BLUP, ML,
      REML) are presented under the hypotheses of both schools of inference, and their
      properties are examined in both cases. The Bayesian approach is discussed in
      cases in which prior information is available, prior information is available
      under certain hypotheses, prior information is vague, and there is no prior
      information. Bayesian prediction of genetic values and genetic parameters are
      presented. Finally, the frequentist and Bayesian approaches are compared from a
      theoretical and a practical point of view. Some problems for which Bayesian
      methods can be particularly useful are discussed. Both Bayesian and frequentist
      schools of inference are established, and now neither of them has operational
      difficulties, with the exception of some complex cases. There is software
      available to analyze a large variety of problems from either point of view. The
      choice of one school or the other should be related to whether there are
      solutions in one school that the other does not offer, to how easily the problems
      are solved, and to how comfortable scientists feel with the way they convey their
      results.

PMID- 11518212
TI  - Developing stochastic epidemiological models to quantify the dynamics of
      infectious diseases in domestic livestock.
AB  - A stochastic model describing disease transmission dynamics for a microparasitic
      infection in a structured domestic animal population is developed and applied to
      hypothetical epidemics on a pig farm. Rational decision making regarding
      appropriate control strategies for infectious diseases in domestic livestock
      requires an understanding of the disease dynamics and risk profiles for different
      groups of animals. This is best achieved by means of stochastic epidemic models.
      Methodologies are presented for 1) estimating the probability of an epidemic,
      given the presence of an infected animal, whether this epidemic is major
      (requires intervention) or minor (dies out without intervention), and how the
      location of the infected animal on the farm influences the epidemic
      probabilities; 2) estimating the basic reproductive ratio, R0 (i.e., the expected
      number of secondary cases on the introduction of a single infected animal) and
      the variability of the estimate of this parameter; and 3) estimating the total
      proportion of animals infected during an epidemic and the total proportion
      infected at any point in time. The model can be used for assessing impact of
      altering farm structure on disease dynamics, as well as disease control
      strategies, including altering farm structure, vaccination, culling, and genetic
      selection.

PMID- 11518213
TI  - Utilizing stochastic genetic epidemiological models to quantify the impact of
      selection for resistance to infectious diseases in domestic livestock.
AB  - This paper demonstrates the use of stochastic genetic epidemiological models for
      quantifying the consequences of selecting animals for resistance to a
      microparasitic infectious disease. The model is relevant for many classes of
      infectious diseases where sporadic epidemics occur, and it is a powerful tool for
      investigating the costs, benefits, and risks associated with breeding for
      resistance to specific diseases. The model is parameterized for transmissible
      gastroenteritis, a viral disease affecting pigs, and selection for resistance to
      this disease on a structured pig farm is simulated. Two genetic models are used,
      both of which involve selection of sires. The first involves selection with the
      assumption of continuous genetic variation (the continuous selection model). The
      second involves selection with the assumption of introgression of a major
      recessive gene that confers resistance (the gene introgression model). In the
      base population, the basic reproductive ratio, R0 (i.e., the expected number of
      secondary cases after the introduction of a single infected animal) was 2.24, in
      agreement with previous studies. The probabilities of no epidemic, a minor
      epidemic (one that dies out without intervention), and a major epidemic were
      0.55, 0.20, and 0.25, respectively. Selection for resistance, under both genetic
      models, resulted in a nonlinear decline in the probability of a major epidemic
      and a decrease in the severity of the epidemic, should it occur, until R0 was
      less than 1.0, at which point the probability of a major epidemic was zero. For
      minor epidemics, the probability and severity of the epidemic increased until R0
      reached 1.0, at which point the probabilities also fell to zero. The epidemic
      probabilities were critically dependent on the location on the farm where
      infected animals were situated, and the relative risks of different groups of
      animals changed with selection. The main difference between the two genetic
      models was in the time scale; the introgression results simply depended on how
      quickly the resistance allele could be introgressed into the population. For the
      introgression model, the probability of a major epidemic declined to zero when
      0.6 of the animals were homozygous for the resistance allele.

PMID- 11518214
TI  - Preference for polyethylene glycol by sheep fed a quebracho tannin diet.
AB  - Tannins decrease food intake by reducing digestion and by causing illness,
      whereas polyethylene glycol (PEG) attenuates the aversive effects of tannins. Our
      objective was to determine whether sheep recognize the benefits of ingesting
      substances such as PEG when consuming tannins. If so, then ingestion of PEG
      should be 1) PEG-specific, 2) a function of previous experience with recovery
      from tannin-toxicosis, and 3) dependent on the presence/absence of tannins.
      During conditioning, lambs in Group 1 (n = 10) were offered a meal of high-tannin
      food, which presumably caused malaise, and then offered PEG (molecular weight,
      3,350), which presumably led to recovery from malaise. Subsequently, lambs
      ingested a control food (wheat straw) that did not have the "medicinal" effects
      of PEG in the absence of the tannin diet. In contrast, lambs in Group 2 (n = 10)
      ingested PEG in the absence of the tannin diet, and they ingested the tannin diet
      only in association with wheat straw. Ingestion of PEG and straw by both groups
      of lambs increased as a function of the presence of tannins in the diet (P <
      0.05). However, when offered a choice among the tannin diet, PEG and straw, or
      when given the tannin diet and then offered a choice between PEG and straw, lambs
      trained to associate PEG with tannins ate more PEG than lambs that ingested PEG
      without tannins (P < 0.05). The responses were apparently PEG-specific; straw
      intake did not differ between groups of lambs during testing (P > 0.05), and
      differences in PEG intake disappeared in the absence of tannins (P > 0.05). In
      summary, our results suggest that lambs fed high-tannin diets discriminated the
      effects of PEG from those provided by a "nonmedicinal" food (straw). Thus, it may
      be possible to formulate PEG supplements that allow herbivores to self-regulate
      intake of PEG under extensive management conditions.

PMID- 11518215
TI  - Selection for lean growth efficiency in Duroc pigs influences pork quality.
AB  - A unique line of Duroc pigs was established by intensive selection for increased
      lean growth efficiency. The objective of this study was to determine the
      influence of this selection strategy on fresh pork quality traits. Two lines of
      Duroc pigs originating from the same foundation herd were evaluated. One line was
      selected for lean growth efficiency over five generations (Select line), and the
      other was a contemporary line maintained from the foundation herd (Control line).
      All pigs in the trial tested negative for the halothane gene. Selection for lean
      growth efficiency resulted in improved lean gain, carcass lean, increased loin
      eye area, and less overall carcass fat. The Select line had significantly lower
      subjective firmness scores in longissimus and significantly greater amounts of
      moisture and protein lost as measurable drip in longissimus, semimembranosus, and
      semitendinosus. There were no differences in subjective color scores or in Hunter
      L, a, and b values between lines. No selection line differences were observed in
      glycolytic potential or ultimate pH. The longissimus and the semitendinosus
      exhibited significantly lower early postmortem pH values in Select line pigs.
      Warner-Bratzler shear values were higher for Select line longissimus chops.
      Degradation of troponin-T was decreased in the Select line longissimus samples.
      This result suggests that reduced degradation of myofibrillar proteins may be
      associated with increased moisture and protein lost during storage. This research
      points out that elimination of the halothane gene will solve some but not all of
      the genetically influenced pork quality problems faced by the industry. The
      Select line of pigs appears to be more prone to producing pork that is soft and
      exudative, indicating a link between soft and exudative pork and some genetic
      selection strategies may exist. Therefore, it appears that selection for some
      economically important traits, such as feed efficiency or increased lean growth
      in the absence of the halothane gene, may compromise pork quality.

PMID- 11518216
TI  - Feeding high levels of vitamin D3 does not improve tenderness of callipyge lamb
      loin chops.
AB  - The objective of this study was to determine whether feeding high doses of
      vitamin D3 7 d before slaughter would increase muscle Ca++ levels and result in
      more tender loin chops. Market lambs (n = 4 callipyge and 4 normal in Exp. 1, and
      n = 16 calipyge and 16 normal in Exp. 2) were randomly and equally assigned to
      feeding groups based on callipyge genotype and experimental diet, (vitamin D3 or
      control). Serum Ca++, muscle Ca++, Warner-Bratzler shear force, and troponin-T
      degradation data were analyzed. In Exp. 1, vitamin D3 was supplemented at 1 or 2
      x 10(6) IU/d. The 2 x 10(6) IU dose resulted in the greatest serum Ca++ reponse
      and was chosen for Exp. 2. In Exp. 2, serum Ca++ concentration was higher (P <
      0.05) for normal and callipyge lambs fed the vitamin D3 diet than for the control
      diet fed lambs. Muscle Ca++ concentrations, however, were not higher (P = 0.28)
      for the vitamin D3-fed lambs. Warner-Bratzler shear values were higher (P < 0.05)
      for callipyge than for normal lambs, but no differences were observed with
      vitamin D3 supplementation. These data were supported by results from Western
      blot analysis of troponin-T degradation, in which no differences were observed
      for vitamin D3 vs control diet lambs at 14 d postmortem. This experiment showed
      that feeding 2 x 10(6) IU/d of vitamin D3 to market lambs, callipyge or normal,
      raised serum Ca++ concentration, but did not increase muscle Ca++ concentration.
      This lack of response in muscle Ca++ was likely the reason that no differences
      were observed for Warner-Bratzler shear force values or troponin-T degradation
      data between the vitamin D3 and control loin chops. A higher dose of vitamin D3
      may be required to improve tenderness.

PMID- 11518217
TI  - Influence of dental carcass maturity classification on carcass traits and
      tenderness of longissimus steaks from commercially fed cattle.
AB  - Two hundred beef carcasses were randomly selected by dental classification (zero,
      two, four, six, or eight permanent incisors) from a population of 11,136
      carcasses harvested by a large commercial beef processor. Warner-Bratzler shear
      force and trained sensory panel evaluations of longissimus thoracis steaks as
      well as cooking and carcass traits were evaluated for differences among dental
      classes. No differences in Warner-Bratzler shear force (P = 0.60), sensory panel
      evaluations (P = 0.64) for tenderness, or percentage of total cooking loss (P =
      0.73) were found among the five dental classes. Longissimus muscle color, USDA
      marbling score, hot carcass weight, adjusted fat thickness, longissimus muscle
      area, and USDA yield grade did not differ among the five dental classes. A
      significant dental classification x sex interaction indicated that heifers
      advanced in skeletal and overall maturity at a much faster rate than steers. An
      increase of intramuscular fat was associated (P < 0.05) with decreased shear
      force (r = -0.31), whereas darkening of the lean (r = 0.16), advancing lean
      maturity (r = 0.21), and increased evaporative cooking loss (r = 0.39) were
      associated (P < 0.05) with increased shear force values. Warner-Bratzler shear
      force measurements were not related to sensory panel overall tenderness scores.
      Carcass traits accounted for a relatively small proportion of the variation in
      tenderness of longissimus steaks, and dental classification was not related to
      tenderness.

PMID- 11518218
TI  - Properties of myofibril-bound calpain activity in longissimus muscle of callipyge
      and normal sheep.
AB  - Properties of the calpain bound to myofibrils in longissimus muscle from
      callipyge or noncallipyge sheep were examined after 0, 1, 3, and 10 d of
      postmortem storage at 4 degrees C. Western analysis has shown that most of this
      calpain is mu-calpain, although the sensitivity of the antibodies used in the
      earlier studies could not eliminate the possibility that up to 10% of the calpain
      was m-calpain. The calpain is bound tightly, and very little is removed by
      washing with the detergent Triton X-100; hence, it is not bound to phospholipids
      in the myofibril. Over 25% of total mu-calpain was bound to myofibrils from at
      death muscle, and this increased to approximately 40% after 1 d postmortem. The
      amount of myofibril-bound mu-calpain increased only slightly between 1 and 10 d
      of postmortem storage. The percentage of autolyzed mu-calpain increases with time
      postmortem until after 10 d postmortem, when all myofibril-bound mu-calpain is
      autolyzed. The specific activity of the myofibril-bound calpain is very low and
      is only 6 to 13% as high as the specific activity of extractable mu-calpain from
      the same muscle. It is unclear whether this low specific activity is the result
      of unavailability of the active site of the myofibril-bound calpain to exogenous
      substrate. The myofibril-bound calpain degrades desmin, nebulin, titin, and
      troponin T in the myofibrils, and also releases undegraded alpha-actinin and
      undergoes additional autolysis when incubated with Ca2+; all these activities
      occurred slowly considering the amount of myofibril-bound calpain. Activity of
      the myofibril-bound calpain was partly (58 to 67%) inhibited by the calpain
      inhibitors, E-64 and iodoacetate; was more effectively inhibited by a broader
      based protease inhibitor, leupeptin (84 to 89%); and was poorly inhibited (43 to
      45%) by calpastatin. Release of undegraded alpha-actinin and autolysis are
      properties specific to the calpains, and it is unclear whether some of the
      myofibril-bound proteolytic activity originates from proteases other than the
      calpains or whether the active site of myofibril-bound calpain is shielded from
      the inhibitors. Activities and properties of the myofibril-bound calpain were
      identical in longissimus muscle from callipyge and normal sheep, although
      previous studies had indicated that the "normal" longissimus was much more tender
      than the callipyge longissimus. Hence, it seems unlikely that the myofibril-bound
      calpain has a significant role in postmortem tenderization of ovine longissimus.

PMID- 11518219
TI  - Technical note: A quick and more sensitive method to identify pork in processed
      and unprocessed food by PCR amplification of a new specific DNA fragment.
AB  - We developed and evaluated a PCR procedure to detect pork in heated and unheated
      meat, sausages, canned food, cured products, and pates using a faster, more
      specific, and more sensitive method than others previously described. Isolation
      of a new DNA-specific porcine repetitive element was performed by nonspecific PCR
      amplification. After analyzing this repetitive sequence, a pair of primers were
      synthesized. To confirm the effectiveness and specificity of this fragment, 55
      pig blood DNA samples (from differents breeds) were tested and positive results
      were obtained. With 200 samples tested from other species, the specific pork
      amplification was not detected. Using this method, we can partially quantify
      degree of contamination, depending on the PCR amplification cycles, detecting up
      to 0.005% pork in beef and 1% pork in duck pate using 30 and 20 PCR amplification
      cycles, respectively. The amount of porcine DNA detected in cattle DNA was 1.25
      and 250 pg when using 30 and 20 amplification cycles, respectively. Pork has been
      identified in both heated and unheated meat products, sausages, canned food,
      hamburgers, and pates. In conclusion, specific PCR amplification of a repetitive
      DNA element seems to be a powerful technique for the identification of pork in
      processed and unprocessed food, because of its simplicity, specificity, and
      sensitivity (with 30 amplification cycles we can detect 0.005% pork).
      Furthermore, it is a very fast method, because 1% pork contamination can be
      detected with 20 PCR cycles. The procedure is also much cheaper than other
      methods based on RFLP-PCR, immunodiffusion, or other techniques that need
      expensive equipment.

PMID- 11518220
TI  - Standardized ileal protein and amino acid digestibility by growing pigs and sows.
AB  - Experiments were conducted to determine the effect of the physiological condition
      of swine on standardized ileal digestibility coefficients (SID). The apparent
      ileal digestibility coefficients were determined for crude protein and amino
      acids in six feed ingredients (corn, barley, wheat, soybean meal, canola meal,
      and meat and bone meal) in growing pigs and in gestating and lactating sows.
      Growing pigs and lactating sows were given free access to their diets, whereas
      gestating sows were allowed to consume only 2 kg of feed daily. The nonspecific
      (basal) endogenous losses of protein and amino acids were determined under
      similar feeding regimens after feeding a protein-free diet. The SID for crude
      protein and amino acids were calculated by correcting the apparent ileal
      digestibility coefficients for the nonspecific endogenous losses of protein and
      amino acids. With a few exceptions, there were no differences (P > 0.05) in the
      SID for crude protein and amino acids between growing pigs and lactating sows.
      Overall, gestating sows had higher (P < 0.05) SID for crude protein and all amino
      acids, except for tryptophan and aspartate, compared with growing pigs. Likewise,
      the SID of most amino acids obtained by gestating sows were higher (P < 0.05)
      than those obtained by lactating sows. Interactions (P < 0.05) between animals
      and diets were observed for gestating sows compared with growing pigs as well as
      gestating sows compared with lactating sows. As a consequence, it is not possible
      to extrapolate data from one feed ingredient to another. On most occasions, the
      lowest SID among the indispensable amino acids was calculated for threonine,
      valine, and lysine. It is concluded that gestating sows fed 2 kg of feed per day
      have higher standardized digestibility coefficients than do growing pigs and
      lactating sows given free access to their diets. This difference may be due to
      differences in daily feed intake rather than to the physiological status of the
      animals.

PMID- 11518221
TI  - Effect of K-diformate in starter diets on acidity, microbiota, and the amount of
      organic acids in the digestive tract of piglets, and on gastric alterations.
AB  - The aim of this investigation was to study the effect of K-diformate on the
      intraluminal pH, microbial composition in digesta and feces, organic acids along
      the digestive tract, and alterations of the gastric epithelium of pigs. Pigs (n =
      36) weaned at 28 d of age were allotted to two groups and fed without (control
      diet) or with 1.8% supplemental K-diformate. Fecal samples were taken from the
      rectum on d 0, 1, 3, 5, 7, 14, 21, and 28 postweaning. Half of the animals from
      each group were killed on d 7 and the other half on d 29 postweaning. Growth
      performance was not different for both groups (P > or = 0.73). The gastric
      epithelium was not negatively affected by K-diformate (P = 0.25). Potassium
      diformate decreased (P < or = 0.04) or tended to decrease (P < or = 0.10) the
      counts of total anaerobic bacteria, lactic acid bacteria, and yeasts in feces and
      digesta samples from the stomach, distal small intestine, cecum, and middle
      segment of the colon. The pH along the gastrointestinal tract of piglets was not
      affected by K-diformate (P > or = 0.30). On d 7, the concentration of lactic acid
      along the gastrointestinal tract was similar with both diets (P = 0.15). On d 29,
      the concentrations of lactic acid tended to be lower along the small intestine (P
      < or = 0.08) and the stomach (P = 0.11) of the pigs fed K-diformate. Formic acid
      in digesta was detected at significant levels only in the distal segment of the
      small intestine of the control pigs (from 4 to 11 mmol/kg of wet digesta),
      whereas considerable amounts were measured in the stomach (from 23 to 40 mmol/kg
      of wet digesta) and all segments of the small intestine (from 7 to 25 mmol/kg of
      wet digesta) in the K-diformate-fed pigs on both days. On d 7, pigs fed the K
      diformate diet had a tendency (P < or = 0.08) to have higher concentrations of
      organic acids (acetic + propionic + butyric) in the digesta of the distal small
      intestine, cecum, and proximal colon. On d 29, both groups had similar
      concentrations of these acids, irrespective of the segment of the
      gastrointestinal tract (P = 0.95). Our study showed that the addition of K
      diformate to a starter diet for piglets decreased total anaerobic bacteria,
      lactic acid bacteria, coliforms, and yeasts in feces and in digesta from various
      segments of the gastrointestinal tract, without affecting the gastric or
      intestinal pH.

PMID- 11518222
TI  - Phosphorus bioavailability, growth performance, and nutrient balance in pigs fed
      high available phosphorus corn and phytase.
AB  - Three experiments were conducted to evaluate P bioavailability, growth
      performance, and nutrient balance in pigs fed high available P (HAP) corn with or
      without phytase. The bioavailability of P in normal and HAP corn relative to
      monosodiumphosphate (MSP) for pigs was assessed in Exp. 1. In a randomized
      complete block design, 96 pigs (average initial BW 9.75 kg) were fed eight diets
      for 28 d. The reference and test diets were formulated by adding P as MSP, HAP,
      or normal corn at 0, 0.75, or 1.5 g/kg to a corn-starch-soybean meal basal diet
      (2.5 g/kg P) at the expense of cornstarch. Plasma inorganic P concentration
      responded linearly (P < 0.05) to supplemental P intake. Estimates of P
      bioavailability from HAP andnormal corn when plasma P was regressed on
      supplemental P intake were 46 and 33%, respectively. In Exp. 2 and 3, pigs were
      fed corn-soybean meal-based diets containing HAP corn or normal corn and 0 or 600
      units of phytase per kilogram in a 2 x 2 factorial arrangement (two corn sources
      and two levels of phytase). In Exp. 2, 48 crossbred pigs (barrow:gilt, 1:1)
      averaging 9.25 kg were used to evaluate growth performance. There were no
      detectable interactions between corn source and phytase for any of the
      performance criteria measured. Pigs receiving normal corn had the lowest (P <
      0.05) BW and rate of gain. Feed efficiency was lower (P < 0.05) in pigs fed
      normal compared with those fed the HAP corn phytase-supplemented diet. In Exp. 3,
      24 crossbred barrows averaging 14.0 kg were used to evaluate nutrient
      digestibility. There were no detectable interactions between corn and phytase for
      any of the N and Ca balance criteria. Nitrogen and Ca retention were improved in
      pigs receiving HAP corn with phytase (P < 0.05). Retention and digestibility of P
      was lowest (P < 0.01) for pigs on normal corn diet without phytase. The
      percentage of P digested and retained was improved and fecal P excretion lowered
      (P < 0.05) by feeding HAP corn. The results of this study indicate that the
      bioavailability and balance of P in HAP corn is superior to that of normal corn.
      The addition of 600 phytase units (Natuphos 600, BASF) to HAP corn-based diets
      further improved P digestibility and reduced P excretion in pigs.

PMID- 11518223
TI  - Growth of thoroughbreds fed a low-protein supplement fortified with lysine and
      threonine.
AB  - Growth and protein status were examined in Thoroughbred foals and yearlings
      offered pasture supplements with different crude protein contents and amino acid
      compositions. Both supplements contained 3.0 Mcal/kg DM, 10% corn oil, 1.4%
      calcium, and three sources of fiber. The control supplement contained 14% CP and
      22% soybean meal, whereas the experimental supplement contained 9% CP and 3%
      soybean meal and was fortified with 0.6% lysine and 0.4% threonine. Mares and
      foals were fed twice daily (0700 and 1400) and kept on 12.14-hectare pastures
      (mixed grass and ladino clover) until weaning (6 mo). Weanlings continued on
      specified supplements and pastures for seven additional months. Physical
      measurements and blood samples were taken monthly for a period of 14 mo.
      Measurements included BW, ADG, body condition (BC), wither height, hip height,
      body length, girth, forearm length, front and hind cannon length, and carpus and
      fetlock circumference. Blood plasma analysis included total protein, albumin,
      creatinine, and urea nitrogen. Effect of diet and time were evaluated by analysis
      of variance with repeated measures. No differences (P > 0.05) were found in
      physical measurements between the control and Lys/Thr groups (ADG 0.7 +/- 0.02
      kg/d, BC 4.9 +/- 0.05) for the observational period. Blood data also showed no
      difference (P > or = 0.05) for the period (albumin 2.9 +/- 0.03 g/dL, total
      protein 5.7 +/- 0.10 g/dL, creatinine 1.1 +/- 0.02 mg/dL). Differences in ADG
      between the control and experimental groups were observed in November (0.73 +/-
      0.06 vs 0.91 +/- 0.04 kg/d, P = 0.01) and December (0.56 +/- 0.04 vs 0.67 +/-
      0.06 kg/d, P = 0.07) and again in April (0.65 +/- 0.12 vs 0.86 +/- 0.06 kg/d, P =
      0.06). These results suggest that the foals offered the Lys/Thr grew at the same
      or greater rates than foals on the control supplement. When a low-protein diet
      was fortified with the first two limiting amino acids, the protein was utilized
      more efficiently for growth and development. This study gives further insight
      into the role of protein quality during a foal's 1st yr of growth.

PMID- 11518224
TI  - Dietary conjugated linoleic acid alters fatty acid composition of pig skeletal
      muscle and fat.
AB  - The dietary dose responsiveness of conjugated linoleic acid (CLA) addition
      relative to the fatty acid profile of edible lean tissue was examined in grower
      pigs treated with or without porcine somatotropin (pST). Gilts and barrows were
      fed CLA at 0, 0.25, 0.5, 1.0, or 2.0% of diet by weight from 20 to 55 kg BW.
      Additional pigs were administered (pST) at 0 or 100 microg x kg BW x d(-1) and
      fed either 0.5 or 2.0% CLA. Animals were fed diets containing 18% CP, 1.2%
      lysine, and 3.5 Mcal of DE/kg at 110% of ad libitum intake. The fatty acid
      profile in latissimus dorsi and dorsal s.c. adipose tissue samples was determined
      by gas chromatography. Dietary CLA replacement of corn oil increased the
      percentage of total fatty acids as stearic acid, whereas the percentages as oleic
      and linolenic acids were reduced in lattisimus muscle. Treatment with CLA + pST
      increased the percentages of linoleic and arachidonic acids while reducing the
      percentages of palmitic and oleic acids in lattisimus muscle. Dietary CLA
      increased the percentages of palmitic and stearic acids in s.c. adipose tissue
      while reducing the percentages of oleic, linoleic, linolenic, and arachidonic
      acids. The percentage of palmitic acid was reduced in s.c. adipose tissue,
      whereas linoleic acid was increased with CLA + pST. No synergistic effect was
      detected between CLA and pST for reducing carcass lipid content in grower pigs.
      However, pST increased the percentage of polyunsaturated fatty acids in
      lattisimus muscle and s.c. adipose tissue while reducing the percentages of
      saturated fatty acids in swine fed CLA.

PMID- 11518225
TI  - The effect of texturized vegetable protein from soy on nutrient digestibility
      compared to beef in cannulated dogs.
AB  - Texturized vegetable protein from soy (TVP) is widely used in canned dog foods,
      but its nutritional value remains in doubt. This study compared apparent prececal
      and total intestinal digestibility when four canned diets containing reciprocal
      proportions of protein from TVP (0 to 57%) and from beef (100 to 43%) were fed to
      eight cannulated dogs. As dietary TVP increased, the following linear changes
      were observed (P < 0.05): prececal and total intestinal protein digestibility
      decreased slightly from 77 to 71% and 86 to 80%, respectively; prececal amino
      acid digestibility decreased in parallel with protein; prececal carbohydrate
      digestibility decreased markedly from 80% to 62% and carbohydrate disappearance
      in the large intestine increased from 8 to 22%; prececal sodium digestibility
      decreased markedly (from 37 to 4%); and prececal potassium digestibility
      decreased (from 93 to 85%). Total intestinal digestibility of sodium and
      potassium decreased little (from 97 to 95% and from 98 to 97%, respectively);
      fecal mass and water content increased markedly (from 98 to 174 g/d and from 61
      to 72%, respectively); and fat digestibility was unaffected. Prececal phosphorus
      digestibility from two diets containing TVP was lower than that from the all-beef
      diet (13 and 17%, vs 26%, P < 0.05). In conclusion, TVP is a useful source of
      protein in canine canned diets because amino acids from TVP are almost as
      digestible as those from beef in the canine intestine. Nevertheless, soy
      carbohydrate is poorly digested and large amounts of TVP inhibit small intestinal
      electrolyte digestibility and increase fecal water content.

PMID- 11518226
TI  - Effect of chromium picolinate and chromium propionate on glucose and insulin
      kinetics of growing barrows and on growth and carcass traits of growing-finishing
      barrows.
AB  - Two experiments were conducted to determine the effects of dietary Cr
      tripicolinate (CrPic) or Cr propionate (CrProp) on growth, carcass traits, plasma
      metabolites, glucose tolerance, and insulin sensitivity in pigs. In Exp. 1, 36
      barrows (12 per treatment; initial and final BW were 20 and 38 kg) were allotted
      to the following treatments: 1) corn-soybean meal basal diet (control), 2) as 1 +
      200 ppb Cr as CrPic, or 3) as 1 + 200 ppb Cr as CrProp. Growth performance data
      were collected for 28 d, and then 23 pigs (seven, eight, and eight pigs for
      treatments 1, 2, and 3, respectively) were fitted with jugular catheters and a
      glucose tolerance test (500 mg glucose/kg BW) and an insulin challenge test (0.1
      IU of porcine insulin/kg BW) were conducted. Both CrPic and CrProp decreased (P <
      0.05) ADG and ADFI but did not affect gain:feed (P > 0.10). Fasting plasma
      glucose, total cholesterol, urea N, insulin, and high-density lipoprotein
      cholesterol:total cholesterol concentrations were not affected (P > 0.10) by
      either Cr source. Pigs fed CrPic had lower (P < 0.02) fasting plasma NEFA
      concentrations than control pigs, but plasma NEFA concentrations of pigs fed
      CrProp were not affected (P > 0.10). During the glucose tolerance test, glucose
      and insulin kinetics were not affected by treatment (P > 0.10). During the
      insulin challenge test, glucose clearance was increased (P < 0.01) in pigs fed
      CrProp but not affected (P > 0.10) in pigs fed CrPic. Glucose half-life was
      decreased (P < 0.03) in pigs fed CrPic or CrProp, but insulin kinetics were not
      affected (P > 0.10). In Exp. 2, 48 barrows (four replicates of four pigs per
      replicate; initial and final BW were 23 and 115 kg) were allotted to the same
      dietary treatments in a growing-finishing study. Average daily gain, ADFI, and
      gain:feed were not affected (P > 0.10) by treatments. Carcass length tended (P =
      0.10) to be greater in pigs fed CrPic than in pigs fed CrProp, but other carcass
      measurements were not affected (P > 0.10). Glucose kinetics from the insulin
      challenge test indicate that both CrPic and CrProp increase insulin sensitivity
      and that both Cr sources are bioavailable.

PMID- 11518227
TI  - Nutrient mobilization from body tissues as influenced by litter size in lactating
      sows.
AB  - Twenty-eight primiparous sows were used to study nutrient mobilization among body
      tissues as influenced by litter size in lactating sows. Litter size was set to 6,
      7, 8, 9, 10, 11, or 12 pigs within 48 h postpartum by cross-fostering. Four sows
      were allotted to each litter size group. Sows had 11.5 +/- 1.3 Mcal of ME and
      39.3 +/- 4.4 g of lysine per day and were killed on d 20.6 +/- 1.1 of lactation.
      Liver, gastrointestinal tract (GIT, composed of the empty stomach, empty small
      and large intestines, cecum and rectum), reproductive tract, and other organs
      (excluding liver, GIT, reproductive tract, and mammary gland) were separated from
      the carcass. Gastrointestinal tracts were manually stripped of contents and
      flushed with water to remove digesta. Hot carcasses were split longitudinally at
      the midline after removing mammary glands and internal organs. Individual organs
      and carcasses were weighed then ground for chemical analysis. Dry matter, crude
      protein, fat, and ash contents were measured. As litter size increased, protein
      mobilization was linearly increased (P < 0.05) in carcass, GIT, and reproductive
      tract. Protein mobilization in liver was quadratically affected by litter size (P
      < 0.05). Fat mobilization was not affected by litter size. The amount of protein
      mobilized from carcass, GIT, liver, and reproductive tract in sows increased by
      641 g as litter size increased by one pig from 6 to 12 pigs after a 21-d
      lactation. Carcass contributed the largest amount of protein (600 g for an
      additional pig) among body tissues, whereas the reproductive tract contributed
      the highest percentage (26%) of its protein among body tissues. Protein
      efficiency from milk to litter weight gain was 72% as litter size increased
      during a 21-d lactation. In feeding lactating sows, effect of litter size on
      nutrient mobilization from various tissues should be considered for minimizing
      the excess tissue mobilization during lactation.

PMID- 11518228
TI  - Conjugated linoleic acid improves feed efficiency, decreases subcutaneous fat,
      and improves certain aspects of meat quality in stress-genotype pigs.
AB  - Conjugated linoleic acid (CLA) was supplemented to crossbred growing-finishing
      barrows (n = 60) at 0.75% of the total diet. Pigs were randomly assigned to the
      CLA or control diets based on stress genotype (negative, carrier, or positive).
      Gain:feed was higher for CLA diet animals (350 g/kg feed) than for control diet
      animals (330 g/kg feed) independent of genotype (P < 0.05). No differences were
      observed for ADG for the diets (P = 0.71) or genotype classes (P = 0.40).
      Postmortem pH was lower (P < 0.01) by 3 h for CLA-supplemented pigs, with no
      differences in ultimate pH. No differences (P = 0.16) were observed for ultimate
      pH between the three genotypes. Conjugated linoleic acid-supplemented pigs
      exhibited less 10th rib fat depth (2.34 cm vs 2.84 cm) and last rib fat depth
      (2.46 cm vs 2.72 cm) than control pigs (P < 0.05). Loin muscle area (LMA) was not
      affected (P = 0.18) by CLA supplementation, but LMA was different (P < 0.02) for
      genotype; positive genotype carcasses had the largest LMA (45.02 cm2) and
      negative carcasses had the smallest LMA (36.44 cm2). Carrier carcasses were
      intermediate for LMA (40.76 cm2). Subjective scores for color were not affected
      (P = 0.98) by CLA but color was different (P < 0.01), with scores of 1.50, 2.40,
      and 3.1 for positive, carrier, and negative genotypes, respectively. Subjective
      marbling scores were increased (P < 0.03) in all genotypes with CLA
      supplementation. Subjective firmness scores were higher (P < 0.06) for CLA
      supplemented pigs and were highly correlated (0.89) to marbling scores. The L*
      values were higher (P < 0.01) for stress-positive pigs at 24 h postmortem. Also,
      L* values were higher (P < 0.01) for CLA-fed pigs over 7 d of shelf storage.
      Sensory characteristics were not different with CLA supplementation for
      tenderness (P = 0.24), juiciness (P = 0.35), or flavor intensity (P = 0.14). This
      study showed that LMA was increased with stress-carrier and stress-positive
      genotypes, but lean color was negatively affected with the presence of the stress
      gene. Conjugated linoleic acid supplementation improves feed efficiency,
      decreases backfat, and improves pork quality attributes of marbling and firmness
      of the longissimus muscle. Furthermore, there is seemingly no interaction between
      the stress-genotype status of pigs and the subsequent effect of CLA on their
      growth and performance.

PMID- 11518229
TI  - Plasma glucose and insulin responses of Thoroughbred mares fed a meal high in
      starch and sugar or fat and fiber.
AB  - Plasma concentrations of glucose and insulin following a meal were compared in
      twelve Thoroughbred mares fed a pelleted concentrate (PC), a traditional sweet
      feed high in sugar and starch (SS), or a feed high in fat and fiber (FF). The
      feeds had similar DE and CP but differed in fat (19, 32, and 166 g/kg DM,
      respectively), NDF (199, 185, and 369 g/kg DM, respectively) and nonstructural
      carbohydrates (574, 645, and 247 g/kg, respectively). Mares were randomly
      assigned to two groups balanced for foaling date and weight. All mares received
      PC in late gestation; then, after foaling, one group was fed SS and the other FF
      for trials in early and late lactation. Mares were placed in stalls and deprived
      of feed overnight. A series of blood samples was collected via a jugular catheter
      from 0 (baseline) to 390 min after consumption of 1.82 kg of feed. Plasma was
      analyzed for glucose and insulin. Baseline values, peak values, and areas under
      curves (AUC) were compared by ANOVA. Baseline values were 74.7 +/- 10.9 mg/dL for
      glucose and 5.86 +/- 1.80 mIU/L for insulin for all diets and stages. Responses
      to PC did not differ between the two groups (P > 0.34), indicating the groups
      were metabolically similar. Peak plasma glucose and insulin concentrations were
      higher (P < 0.001) in the SS group than in the FF group during early and late
      lactation. Similarly, glucose and insulin AUC were larger (P < 0.003) in SS than
      in FF during early and late lactation. These results indicate that metabolic
      fluctuations are moderated by the replacement of sugar and starch with fat and
      fiber. This replacement may reduce the risk of certain digestive and metabolic
      disorders that have been linked to feeding meals of grain-based concentrates to
      pregnant or lactating mares.

PMID- 11518230
TI  - Complex interaction of ergovaline with 5-HT2A, 5-HT1B/1D, and alpha1 receptors in
      isolated arteries of rat and guinea pig.
AB  - Vascular effects of ergovaline mediated by 5-hydroxytryptamine(HT)2A, 5-HT1B/1D,
      and alpha1 receptors were studied in isolated arterial preparations of rat and
      guinea pig. In rat tail artery ergovaline behaved as a potent contractile partial
      agonist showing an agonist potency (pEC50) of 8.86 +/- 0.03, a maximum response
      (Emax) of 59 +/- 2% with respect to 5-HT, and a partial agonist affinity (pK(P))
      of 8.51 +/- 0.06. Ergovaline was equipotent with ergotamine (pEC50, 8.69 +/-
      0.07; Emax, 52 +/- 4%; pK(P), 8.36 +/- 0.11). Contractile responses to ergovaline
      and ergotamine were surmountably antagonized by the 5-HT2A receptor antagonist
      ketanserin (3 nM). Antagonist affinity (apparent pA2) for ketanserin against
      ergovaline and ergotamine was 9.19 +/- 0.08 and 9.36 +/- 0.17, respectively.
      Ergovaline showed extremely slow on-set and off-set kinetics in rat tail artery.
      The construction of cumulative concentration-response curves required about 4 h,
      and the contractile response to ergovaline (30 nM), which completely abolished
      the subsequent contractile response to 5-HT (10 nM to 1 mM), could not be
      reversed by wash-out. In guinea pig iliac artery moderately precontracted with
      prostaglandin F2alpha (0.05 to 0.5 microM) ergovaline behaved as an agonist
      (pEC50, 7.71 +/- 0.10) with a potency similar to that of 5-HT (pEC50, 7.60 +/-
      0.05). The contractile response to ergovaline was inhibited by the 5-HT1B/1D
      receptor antagonist GR127935 (10 nM). The apparent pA2 value for GR127935 against
      ergovaline was 8.90 +/- 0.12. Ergovaline (10 nM) produced no contractile response
      in guinea pig iliac artery when added before the PGF2alpha-induced precontraction
      but caused insurmountable blockade of the contractile response to the 5-HT1B/1D
      receptor agonist 5-carboxamidotryptamine (5-CT). The apparent pA2 value for
      ergovaline against 5-CT was 8.56 +/- 0.18. In rat thoracic aorta ergovaline (2
      microM) activated alpha1 adrenoceptors only with low efficacy (Emax, 12 +/- 3%)
      but surmountably antagonized norepinephrine-induced contractions with a pK(P) of
      7.07 +/- 0.12. It is concluded that the powerful constrictor effect of ergovaline
      mediated by activation of vascular 5-HT2A and 5-HT1B/1D receptors may explain the
      vascular symptoms of fescue toxicosis observed in livestock grazing tall fescue
      pastures infected with the endophytic fungus Neotyphodium coenophialum.

PMID- 11518231
TI  - Improved synchrony of estrus and ovulation with the addition of GnRH to a
      melengestrol acetate-prostaglandin F2alpha synchronization treatment in beef
      heifers.
AB  - The objective of this experiment was to determine the effect of a GnRH injection
      within a melengestrol acetate (MGA)-PGF2alpha (PGF) estrus synchronization
      protocol on follicular dynamics and synchronization of estrus. Pubertal crossbred
      beef heifers (n = 34) were randomly assigned to one of two treatments. Both
      treatment groups were fed MGA (0.5 mg x hd(-1) x d(-1)) for 14 d and injected
      (i.m.) with PGF (25 mg of Lutalyse) 19 d after MGA withdrawal. Melengestrol
      acetate was delivered in a feed supplement of 1.8 kg x hd(-1) x d(-1). Seventeen
      heifers received an injection of GnRH (100 microg Cystorelin) 12 d after MGA
      withdrawal and 7 d before PGF. The control group (n = 17) received only MGA-PGF.
      Estrus was detected four times/d for 7 d beginning on the day PGF was injected.
      Transrectal ultrasonography was performed daily on eight heifers from each
      treatment to monitor ovarian activity and characterize changes in follicular
      dynamics after MGA withdrawal and until ovulation after PGF. Each of the GnRH
      treated heifers either ovulated or had a luteinized dominant follicle following
      GnRH and subsequently initiated a new follicular wave (8/8, 100%). All GnRH
      treated heifers (17/17, 100%) and 94% of controls (16/17) exhibited estrus after
      PGF. Estrus was exhibited over a 132-h period (12 to 144 h) for control heifers
      compared with 60 h (48 to 108 h) for GnRH-treated heifers. The peak synchronized
      period for both treatments was between 48 and 72 h after PGF, during which time
      76% (13/17) of the GnRH-treated heifers exhibited estrus compared with 63%
      (10/16) for controls. Seventy-one percent (12/17) of the GnRH-treated heifers
      exhibited estrus from 48 to 60 h after PGF, compared with 38% (6/16) for controls
      (P < 0.05). In summary, injection of GnRH within a 14- to 19-d MGA-PGF protocol
      increased the synchrony of estrus during the synchronized period and concentrated
      the period of detected estrus. This protocol may offer potential for the fixed
      time insemination of replacement beef heifers.

PMID- 11518232
TI  - Relation of growth hormone response to growth hormone-releasing hormone before
      weaning and postweaning growth performance in beef calves.
AB  - Previously, GH response to GHRH challenge at weaning has been shown to be
      indicative of ADG during a standard postweaning growth performance test in Angus
      cattle. In this study, we tested the hypothesis that GH response to GHRH before
      weaning would predict postweaning ADG. Bulls with the highest and lowest GH
      responses to GHRH over a 3-yr period, relative to their contemporaries, were used
      as sires, to allow for examination of the persistence of GH response to GHRH
      through selection. The selected calves in this study were sired by one of four
      Angus bulls chosen based on their GH response to GHRH (high response, n = 2; low
      response, n = 2). Forty-nine Angus calves (bulls, n = 24; heifers, n = 25) were
      challenged with GHRH at approximately 60, 105, and 150 d of age and at weaning
      (219 d; SD = 25). Blood samples were taken immediately prior to and 10 min
      following an i.v. clearance dose of 4.5 microg of GHRH/100 kg BW and, 2 h later,
      immediately prior to and 10 min following a challenge dose of either 1.5 or 4.5
      microg of GHRH/100 kg BW. Two hours later, the procedure was repeated, with each
      calf receiving the other challenge dose. Body weight was measured every 28 d and
      ADG was calculated over a 140-d growth performance test (heifers and bulls
      maintained separately). Data were log-transformed for statistical analyses. In
      the selected bulls and heifers, response of GH to 1.5 microg of GHRH/100 kg BW at
      60 and 105 d of age was positively related (P < 0.05) to postweaning ADG.
      Response to 4.5 microg of GHRH/100 kg BW at 105 d of age and at weaning was
      positively related (P < 0.01) to postweaning ADG. Inclusion of sire in the
      analysis improved the relationship between GH response and ADG for calves of
      sires with high GH responses from R2 = 0.18 (P = 0.01) to R2 = 0.33 (P = 0.02).
      When the GH response to GHRH of the unselected calves at weaning was added to the
      data from the selected animals and analyzed, the GH response of the bulls was
      related to postweaning ADG (R2 = 0.09; P = 0.04). In conclusion, GH response to
      GHRH as early as 60 d of age is indicative of postweaning ADG in beef cattle. In
      addition, the relationship between GH response to GHRH and postweaning ADG is
      improved with selection for greater GH response to GHRH.

PMID- 11518233
TI  - The effects of degradable and undegradable intake protein on the performance of
      lactating first-calf heifers.
AB  - Two 60-d experiments were conducted to evaluate the effects of supplementing
      degradable (DIP) and(or) undegradable (UIP) intake protein on the performance of
      lactating first-calf heifers. Diets were formulated to meet the requirements for
      either DIP, metabolizable protein (MP), or both when diets contained low-quality
      grass hay and an efficiency of microbial protein synthesis estimate of 10%. In
      Exp. 1, 32 individually fed first-calf heifers (avg 395 kg) were allotted to a 2
      x 2 factorial arrangement of treatments (main effects of DIP, MP, and DIP x MP
      interaction) 1 d after calving. Cows consumed a basal diet of chopped crested
      wheat grass hay (4.3% CP, 67% DIP) ad libitum. Supplemental DIP and UIP were
      supplied by varying the ratios of soybean meal (75% DIP) and a heat-treated,
      protected soybean meal (70% UIP). Cow weight gain was better (P < 0.01) when
      adequate DIP was supplied than when DIP was deficient. However, calf weight gain
      was not increased by supplementing the cow with DIP. Supplemental UIP did not (P
      > 0.40) improve cow or calf weight gain. Blood urea N levels were higher (P <
      0.01) for cows receiving supplemental DIP and UIP. However, milk production
      estimates were similar among treatments, as were digestibilities of OM and ADF.
      Nitrogen digestibility was greater when supplemental DIP was fed, but providing
      additional UIP did not (P = 0.15) change N digestibilities. Experiment 2
      evaluated similar supplements using the same experimental design to determine
      changes in cow and calf weight gain, body condition score, and pregnancy rate.
      Seventy-two first-calf heifers (avg 441 kg) were allotted to supplement
      treatments 1 d after calving and were fed grass hay (5% CP, 53% DIP, 10%
      microbial efficiency) for ad libitum consumption for 60 d. Supplements were
      individually fed three times/week. Varying the ratios of soybean meal, heat
      treated soybean meal, and corn gluten meal provided additional DIP and UIP.
      Unlike in Exp. 1, supplemental UIP improved (P < 0.05) cow weight gain. Calves
      from dams supplemented with DIP gained 5 kg more weight after 60 d than calves
      from dams deficient in DIP. Pregnancy rates in the fall were similar (P = 0.90)
      among treatments. These data suggest that DIP was more limiting in Exp. 1 than
      was UIP. Supplementing UIP in Exp. 2 improved cow weight gains but did not
      improve calf gains. Data suggest that the efficiency of microbial protein
      synthesis for this forage-based diet was probably less than 10%.

PMID- 11518235
TI  - Rapid communication: Mapping of the pro-opiomelanocortin (POMC) gene to pig
      chromosome by linkage analysis using a PCR-RFLP.

PMID- 11518234
TI  - Effect of forage:concentrate ratio on ruminal digestion and duodenal flow of
      fatty acids in ewes.
AB  - The objective of this study was to determine the forage:concentrate ratio that
      would provide the greatest duodenal flow of unsaturated fatty acids in ewes
      supplemented with soybean oil and to determine how diets differing in forage
      content affect flow of conjugated linoleic acid (CLA) and trans-vaccenic acid
      (18:1(trans-11)). Five mature ewes (66.5 +/- 12.8 kg) fitted with ruminal and
      duodenal cannulas were used in a 5 x 5 Latin square experiment. Diets were
      isonitrogenous and included bromegrass hay, cracked corn, corn gluten meal, urea,
      and limestone. Dietary fat was adjusted to 6% with soybean oil. Five ratios of
      forage:concentrate (18.4:81.6, 32.2:67.8, 45.8:54.2, 59.4:40.6, and 72.9:27.1)
      were fed at 1.3% of BW daily in equal allotments at 0630 and 1830. After 14 d,
      Cr2O3 (2.5 g) was dosed at each feeding for 7 d and ruminal, duodenal, and fecal
      collections were taken for the next 3 d. Duodenal flow of 18:0 increased linearly
      (P < 0.01) with dietary forage. Duodenal flow of 18:1(cis-9) and 18:2(cis-9,12)
      decreased (P < 0.001) but duodenal flow of 18:3(cis-9,12,15) increased (P < 0.01)
      with increased dietary forage. Biohydrogenation of dietary unsaturated fatty
      acids increased (P < 0.001) as dietary forage increased, which was concomitant
      with increased ruminal pH. Duodenal flow of 18:2(cis-9,trans-11) increased
      linearly (P < 0.01) with increased dietary forage but increased abruptly when
      forage was fed at 45.8%. Duodenal flow of the trans-10, cis-12 and cis-10, cis-12
      CLA isomers decreased as dietary forage increased, but flow tended to increase on
      the highest-forage diet, resulting in both linear (P < 0.01) and quadratic (P <
      0.01) effects. Duodenal flow of 18:1(trans-11) decreased from 8.28 g/d on the
      18.4% forage diet to 5.47 g/d on the 59.4% forage diet then increased to 7.29 g/d
      on the highest-forage diet (quadratic, P < 0.1). Duodenal flow of 18:1(trans-11)
      was 27- to 69-fold greater than flow of CLA. We conclude that when ewes were fed
      a 6% crude fat diet duodenal flows of dietary fatty acids changed incrementally
      as dietary forage was increased, whereas changes in flows of CLA isomers seemed
      to be more abrupt. Biohydrogenation changes were gradual with diet, suggesting a
      gradual shift in ruminal microbial populations with increasing forage. Finally,
      the highest-concentrate diet supported the greatest duodenal flows of dietary
      unsaturated fatty acids, as well as the highest flow of 18:1(trans-11).

PMID- 11518236
TI  - Observation of yeast cell movement and aggregation in a small-scale MHz
      ultrasonic standing wave field.
AB  - Aggregation of suspended yeast cells in a small-scale ultrasonic standing wave
      field has been monitored and quantified. The aggregation effect is based on the
      acoustic radiation force, which concentrates the cells in clumps. The ultrasonic
      chamber employed (1.9 MHz, one wavelength pathlength) had a sonication volume of
      60 microl. The aggregation process was observed from above the transducer through
      a transparent glass reflector. A distinct, reproducible, pattern of clumps formed
      rapidly in the sound field. The sound pressure was estimated experimentally to be
      of the order of 1 MPa. Microscopic observations of the formation of a single
      clump were recorded onto a PC. The time dependent movement patterns and
      travelling velocities of the cells during the aggregation process were extracted
      by particle image velocimetry analysis. A time dependent change was seen in the
      particle motion pattern during approach to its completion of clump formation
      after 45 s. Streaming eddies were set-up during the first couple of seconds. The
      scale of the eddies was consistent with Rayleigh micro-streaming theory. An
      increase in the travelling velocity of the cells was observed after 30 s from
      initially about 400 microm s(-1) to about 1 mm s(-1). The influence of a number
      of mechanisms on particle behaviour (e.g. micro-streaming, particle interactions
      and convective flow) is considered. The experimental set-up introduced here is a
      powerful tool for aggregation studies in ultrasonic standing waves and lays the
      foundation for future quantitative experiments on the individual contributions of
      the different mechanisms.

PMID- 11518237
TI  - Investigation of enhancement of two processes, sedimentation and conjugation,
      when bacteria are concentrated in ultrasonic standing waves.
AB  - Cells aggregate and can be recovered from suspension when exposed to an
      ultrasonic standing wave field. The acoustic force on individual cells in a
      standing wave decreases with particle volume. A plane ultrasonic field generated
      by a transducer driven at 3.3 MHz was used here to investigate the removal of
      Escherischia coli, cells with dimensions of the order of 1.0 microm, from batch
      suspension by sedimentation over a range of concentrations (10(3) to 10(10) cells
      ml(-1)). Cell removal efficiencies greater than 90% were achieved at initial
      concentrations of 10(10) cells ml(-1). Removal efficiencies decreased gradually
      to zero, as initial bacterial concentration was reduced to 10(7) cells ml(-1). It
      was found that, when low concentrations of E. coli (10(3) to 10(5) cells ml(-1))
      were added to suspensions of larger particles (i.e. yeast cells) that were of
      sufficient concentration to form aggregates in the sound field, E. coli could be
      harvested to an efficiency of 40%. The results imply that the E. coli became
      trapped and sediment with aggregates of larger particles. Some strains of
      bacteria are capable of DNA transfer by conjugation. The transfer rate of E. coli
      RP4 plasmid is order of magnitudes greater when conjugation occurs on solid
      medium rather than in liquid suspension. We have investigated whether the
      conjugation rate would also be higher in ultrasonically induced E. coli clumps
      than in free suspension. The donor strain was mixed with a recipient strain of E.
      coli, then sonicated in a capillary at 4.6 MHz in a tubular transducer for 5 min.
      The bacteria aggregated successfully. Results showed a three-fold increase in the
      rate of conjugation compared to a liquid mating control.

PMID- 11518238
TI  - Sub-micron particle manipulation in an ultrasonic standing wave: applications in
      detection of clinically important biomolecules.
AB  - Separation of particles from the suspending phase is of interest, among others,
      to clinical analysts. A system that enables manipulation of sub-micron sized
      particles in suspensions of analytical scale volume (10-50 microl) using a non
      cavitating ultrasonic standing wave is described. Particle suspensions, contained
      in glass capillary tubes of 1-2 mm internal dimension, are treated on the axis of
      a tubular transducer generating a radial standing wave field at 4.5 MHz.
      Microparticles (of average diameter range 0.3-10 microm) suspended in buffer are
      concentrated within seconds at preferred regions separated by submillimetre
      distances. Concentration of suspended latex particles was inhibited in solutions
      containing protein at levels similar to those occurring in clinical specimens
      when the suspensions were sonicated in capillaries of circular cross-section.
      This effect was associated with acoustic streaming of the suspending fluid.
      Silica microparticles (more dense and less compressible than latex) could be
      concentrated in the presence of streaming. Latex particles concentrated readily
      in square cross-section capillaries where no streaming was observed. With sub
      micron particles, the geometry of the sample chamber, the suspending phase
      composition and the size, density and compressibility of the microparticles all
      influence particle manipulation. The radial standing wave system has been used to
      enhance agglutination of antibody-coated latex microparticles in the presence of
      antigen allowing rapid and highly sensitive detection of clinically important
      biomolecules. The sensitivity of conventional diagnostic tests for microbial
      antigen has been improved by application of ultrasound and clinical utility has
      been demonstrated, in particular, for detection of meningitis-causing bacteria.

PMID- 11518239
TI  - Comparison of different types of ceramic hydroxyapatite for the chromatographic
      separation of plasmid DNA and a recombinant anti-rhesus D antibody.
AB  - The chromatographic properties of three types of ceramic hydroxyapatite (HAP) are
      compared. All three materials were prepared by sintering the original
      precipitate, albeit at different temperatures (400, 700 and 1000 degrees C for
      type I, II and III HAP, respectively). The three materials differed in pore size
      and pressure limits (both lowest for type I and highest for type III). Type I and
      II HAP had an average particle diameter of 20 microm. The particle size of the
      type III material was 40 microm. HAP-beads were slurry-packed into 4 x 25-mm
      stainless steel columns and investigated for the chromatographic isolation of
      plasmid DNA from clarified E. coli lysates and of a recombinant human antibody
      from CHO cell culture supernatants respectively. The chromatographic performance
      of the three types of HAP showed significant differences, which were correlated
      to the binding capacities of the materials for (linearized) plasmids of different
      size (4.7, 10.3 and 11.4 kb) and proteins of different isoelectric point
      (lysozyme, pI = 10.5; anti RhD antibody, pI = 8.3; beta-lactoglobulin, pI = 4.9).
      The accessibility of the adsorptive surface (pore size) but also the types of
      binding sites on the HAP-surface (P/C-site ratio) are proposed as determining
      factors for the chromatographic behavior.

PMID- 11518240
TI  - Breakdown of immobilisation/separation and morphology changes of yeast suspended
      in water-rich ethanol mixtures exposed to ultrasonic plane standing waves.
AB  - Some physiological/morphological changes have been reported before, when
      suspended yeasts have been irradiated with well-defined ultrasonic standing, as
      well as propagating, plane waves around 2.2 MHz, as used in ultrasonic
      coagulation, e.g., for cell filtering. Thus we used yeast as a biological model
      to explore the reasons for both those morphology changes and some unusual
      macroscopic behaviour in the case of water-rich ethanol mixtures when used as
      carrier liquid. When the cells were suspended in 12% (v/v) ethanol-water mixture
      separation was greatly reduced; the yeast cells were not retained in the pressure
      nodal planes of the standing wave, but mixed turbulently through the separation
      system. How this behaviour alters the efficiency of retention/immobilisation was
      measured. As the viability of the yeast was decreased as well the morphology of
      the cells was examined using transmission electron microscopy. Two effects,
      according to the type of assessment, were evident; a disruption of the cells
      vacuole and also damage to the cell wall/membrane complex. The extent of the
      alterations in vacuole structure with sonication time, utilising a fluorescent
      vacuole membrane dye, was measured. Transient cavitation was not detected and
      thus could be excluded as being responsible for the observed effects. Other
      possible reasons for the disruption of the intracellular compartments may be
      acoustic pressure, displacement or other, secondary effects like (sub) harmonic
      cavitation. The investigations contribute to a better understanding of the
      physical conditions experienced when a cell is stressed in a high-frequency
      ultrasonic wave in the MHz range.

PMID- 11518241
TI  - PCR identification of Salmonella cells in food and stool samples after
      immunomagnetic separation.
AB  - The purpose of the present study was to investigate the application of various
      sample preparation methods (cell washing before lysis, purification of DNA using
      phenol extraction method, immunomagnetic separation-IMS) for the final PCR
      identification of Salmonella cells. The presence of PCR inhibitors in processed
      food products (milk powder and dried eggs) can be the cause of false-negative
      results in PCR without IMS of target cells. It was also demonstrated that IMS-PCR
      was successfully used for identification and quick confirmation of untypical
      Salmonella strains isolated from human stool samples and rabbit meat. However,
      IMS cannot eliminate intracellular PCR inhibitors present in immunoseparated
      Salmonella cells. These inhibitors must be taken into consideration in evaluation
      of PCR procedure.

PMID- 11518243
TI  - Evidence-based dentistry and health services research: is one possible without
      the other?
AB  - Barriers have been identified in the literature to the implementation of evidence
      based practice in dentistry. A major concern is the lack of rigorous evidence for
      clinical practices. Little attention has been given to the lack of rigorous
      health services research. Evidence-based practice is more about effectiveness
      than efficacy and will influence the type of research that characterizes health
      services research (HSR) because it involves levels of data below that of the
      random controlled trials, involves questions about the appropriateness of care,
      and involves examining the structure, process, and outcomes of care. The need for
      HSR can be seen by examining the appropriateness of dental care and health
      related quality of life outcomes. The conclusion to be drawn is that evidence
      based dentistry needs HSR if it is to fulfill the promise currently held for it
      in the profession.

PMID- 11518242
TI  - Fractionation of whey proteins with a hexapeptide ligand affinity resin.
AB  - The isolation of individual proteins from whey would allow production of more
      consistent and reliable products by the food industry and possibly would also
      increase their use in the pharmaceutical industry. Alpha-lactalbumin is the
      second most prevalent protein in bovine milk whey and has many uses including
      serving as an excellent protein source in infant formulas, power drinks and other
      beverages that require soluble, nutritional protein. In this study, we describe
      two methods for production of alpha-lactalbumin from whey protein isolate using
      bioselective adsorption. The use of a peptide ligand (WHWRKR) attached to a resin
      allowed production of an alpha-lactalbumin-rich fraction with a purity of 90.6%
      and a recovery of 47.9%, while also producing other fractions of commercial
      interest. The combined use of an amino resin followed by the WHWRKR resin produce
      a highly purified alpha-lactalbumin (100%) with a yield of 35.2%.

PMID- 11518244
TI  - Rationalizing the dental curriculum in light of current disease prevalence and
      patient demand for treatment: form vs. content.
AB  - The premise of this paper is that the form and content of dental education do not
      reinforce each other. What results is suboptimal learning; dissatisfied students;
      difficulty generating excitement among the brightest to consider careers in
      dental education; erosion of dentists' self-identity as men and women of science;
      and doubts over whether dental schools can continue as the primary providers of
      oral health education. A need for reform exists because dental curricula must be
      responsive to changes in current and projected disease demographics, to advances
      in science and technology, and to a changing societal culture affecting patient
      demand for treatment. Today's dilemma is that dental schools need to continue to
      graduate competent practitioners to meet present clinical needs while also
      preparing students for a radically different kind of practice in the future.
      Possible approaches to resolve this dilemma include: a shift between what
      constitutes general practice and what constitutes specialty practice; and, the
      implementation of an asynchronous-distributed model of dental education. Such
      changes will likely be independently accompanied by changes in the role of
      universities in society in general that could make feasible many, now
      unthinkable, alternative vehicles for providing dental education.

PMID- 11518245
TI  - Teaching ethics in dental schools: trends, techniques, and targets.
AB  - The importance of promoting ethical behavior in dental students is reflected in
      the emphasis on formal ethics teaching within the curricula of most dental
      schools. Over the last three decades, dental educators have addressed the need
      for ethics training and examined varied teaching approaches. Today, state-of-the
      art ethics education has moved from purely didactic instruction to more
      interactional teaching methods that promote student introspection and group
      problem-solving. This paper provides an overview of trends in ethics teaching in
      dental schools and the current teaching approaches advocated in health science
      schools. In addition, future needs in dental ethics education are explored
      including the importance of addressing the unique aspects of the dental education
      environment.

PMID- 11518246
TI  - Implications for dental education of a dental school-initiated practice research
      network.
AB  - The Case Western Reserve University (CWRU) School of Dentistry has organized a
      research network of 210 general dentists in northern Ohio. Seventeen of these
      dentists have volunteered to serve on a steering committee, for the purpose of
      generating research questions and helping with network organization. To enable
      the practitioners to investigate questions of interest in their practices,
      faculty in the CWRU schools of Dentistry and Medicine provide consultation to
      network dentists, as needed, with regard to research design, implementation, and
      analysis. In turn, the network serves as a resource for the dental school,
      facilitating faculty development, encouraging the development of new research
      programs, and providing an opportunity for students throughout the university to
      become involved in dental practice research. To date, faculty members have
      initiated studies of dental practice that include a survey of dentists' attitudes
      toward tobacco, a weekly return caries study, and a direct observation study of
      general dental practice. The network provides a research "laboratory" for the
      dental school, enabling clinical faculty to participate in research concerning
      dental practice. It has also stimulated a major re-examination of several
      curriculum elements in the school.

PMID- 11518247
TI  - The use of specific dental school-taught restorative techniques by practicing
      clinicians.
AB  - In 1995, a survey requesting information about the utilization of certain
      prosthodontic techniques was mailed to 3,544 graduates of a midwestern dental
      school. Responses were received from 1,455 alumni, representing a 41 percent
      return rate. In general, the results are consistent with international and
      national trends and show significant disparity in the utilization rates of
      certain procedures between general dentists and prosthodontists, as well as a
      disconnect between what is taught in the undergraduate dental educational program
      and what is applied in practice. For example, while prosthodontists typically
      apply what was taught in their educational program, utilization rates of general
      dentists for the facebow was 29.64 percent; the custom tray 68.48 percent; border
      molding 58.67 percent; altered casts 24.10 percent; custom posts 49.29 percent;
      prefabricated posts 67.54 percent; and semi-adjustable articulators 50.64
      percent. While no solutions to this disconnect are offered the authors do pose
      important questions that must be addressed by the dental educational community.

PMID- 11518248
TI  - Educational research in schools of dentistry.

PMID- 11518249
TI  - Responding to the need for faculty development: a survey of U.S. and Canadian
      dental schools.
AB  - The Office of Professional Development at The University of Texas-Houston Health
      Science Center Dental Branch was established in November 1996 in order to meet
      the professional development needs of the faculty, staff, and administration.
      Although other dental schools share similar needs, our research revealed no study
      to determine how dental schools managed their faculty development needs.
      Therefore, a preliminary survey to collect data about offices similar to ours was
      developed and sent to the deans of fifty-four U.S. schools including Puerto Rico
      and ten Canadian schools. Thirty-seven schools (58 percent) responded, and it was
      determined that five schools (14 percent) had Offices of Professional Development
      and seven (19 percent) had Offices of Faculty Affairs. Based on these results, an
      expanded follow-up survey was conducted. The respondents were asked to indicate
      1) which entity within the school was primarily responsible for handling faculty
      development, and 2) which entity actually sponsored each of eighteen faculty
      development activities. With a response from thirty-three U.S. schools (61
      percent) and six Canadian schools (60 percent), six administrative structures
      (models) for faculty development were identified: 1) Office of Academic Affairs,
      2) Departmental Chair, 3) a Faculty Development Committee, 4) an Office of the
      Dean, 5) an Office of Faculty/Professional Development, and 6) Other Resources.

PMID- 11518250
TI  - Patients are not equally susceptible to periodontitis: does this change dental
      practice and the dental curriculum?
AB  - In the 1960s and 1970s, data became available indicating that most of the adult
      population had periodontal disease and that effective bacterial removal prevented
      and treated periodontitis. This information led to a systematic approach to the
      management of periodontal disease and influenced teaching of periodontics in
      dental schools. We now know that most adults have only gingivitis and very mild
      localized periodontitis. A small percentage, albeit representing substantial
      numbers, of adults have generalized severe periodontitis. We also recognize that
      a few currently known and measurable risk factors, including diabetes, smoking,
      and genetics, can identify the patients who are at risk for the severe
      generalized cases that require extensive therapy and intensive prevention, as
      well as patients at risk for a less-predictable response to treatment. This
      review will discuss the evidence that supports the change in our knowledge and
      understanding of periodontal disease. The question now becomes at what point, and
      how, do we integrate this new knowledge into the dental curriculum?

PMID- 11518251
TI  - Colonization is a crucial factor in oral candidiasis.

PMID- 11518252
TI  - Annual ADEA survey of dental seniors--2000 graduating class.

PMID- 11518253
TI  - The contribution of MD-PhD training to academic orthopaedic faculties.
AB  - Little is known about the distribution of research-trained physicians across the
      various specialties. To document the extent to which MD-PhD programs are a source
      of research-trained faculty for orthopaedic departments, this study examined the
      specialty choices of graduates of the Medical Scientist Training Program (MSTP)
      from 1964 to 1994. The MSTP, a combined MD-PhD program supported by the National
      Institute of General Medical Sciences, (NIGMS), produces roughly 25% of all MD
      PhDs in the US. METHODS: Copies of the appendices from training grant
      applications containing information on MSTP graduates were obtained from the
      NIGMS. Also, a questionnaire was mailed to 116 university-affiliated orthopaedic
      surgery departments asking how many faculty were MD's, PhDs or MD-PhDs. RESULTS:
      Records were obtained for all MST programs. Information on postdoctoral training
      and/or a current position was reported for 1615 graduates who earned both MD and
      PhD. Of these graduates, 277 chose non-clinical paths. The other 1338 entered a
      residency or internship. Of these, 593 were still in residency training, 566 were
      academic faculty members and 130 were in private practice. In the records, 12
      (0.9%) were listed as orthopaedic surgical residents (6) or faculty (6). At this
      time, all 12 have completed training, and 11 are in academic practice. Eighty
      three departments replied to the questionnaire. In that sample of 1761 faculty
      positions, 1478 were MDs, 217 were PhDs and 36 (2.0%) were MD-PhDs. CONCLUSION:
      Despite robust support of MD-PhD programs, the number of dual degree recipients
      on orthopaedic faculties is small when compared to the relative size of the
      specialty. Other sources of research-trained staff should perhaps be developed.

PMID- 11518254
TI  - Genetic loci influencing natural variations in femoral bone morphometry in mice.
AB  - This study identifies genetic loci affecting femoral bone length and width
      measures in mature mice. Sixteen month old female F2 progeny of a C57BL/6J and
      DBA/2J intercross were examined for femur length and width of the femoral head,
      intertrochanteric region and three locations of the diaphysis using digitized
      images of femur radiographs obtained in the anterior-posterior and lateral
      projections. A genome wide linkage map was constructed using microsatellite
      markers at an average density of 20 cM, and quantitative trait locus analysis
      used to identify regions of the genome showing linkage with the traits measured.
      Femur length showed significant linkage with loci on proximal chromosome 3 (lod
      6.1), and suggestive linkage with a locus on chromosome 14. A major locus on mid
      chromosome 7 controlled width of the diaphysis (lod 6.8). Other loci were
      identified on chromosomes 2 and 4. Width at the intertrochanteric region had
      suggestive linkage with loci on chromosomes 6 and 19. No loci were found with
      linkage for width of the femoral head. Candidate genes related to bone
      development or metabolism are present at most of these loci. These findings show
      that genetic regulation of femoral bone morphology is complex, and are consistent
      with the distinct biologic processes that control longitudinal and lateral growth
      of the femur.

PMID- 11518255
TI  - Osteoprotegerin ameliorates sciatic nerve crush induced bone loss.
AB  - This study examines the ability of osteoprotegerin (OPG) to prevent the local
      bone resorption caused by sciatic nerve damage. Sixty-five 18-week-old male mice
      were assigned to one of six groups (n = 10-11/group). A baseline control group
      was sacrificed on day zero of the 10-day study. The remaining groups were placebo
      sham operated, placebo nerve crush (Plac NC) operated, 0.1 mg/kg/day OPG + nerve
      crush (LOW), 0.3 mg/kg/day OPG + nerve crush (MED), and 1.0 mg/kg/day OPG + nerve
      crush (HI). Nerve crush or sham operations were performed on the right leg. The
      left leg served as a contralateral control to the nerve crushed (ipsilateral)
      leg. The difference in mass between the right and left femur and tibia was
      examined. Additionally, quantitative histomorphometry was performed on the right
      and left femur and tibia diaphyses. Nerve crush resulted in a significant loss of
      bone mass in the ipsilateral side compared to the contralateral side. Bone mass
      for the ipsilateral bones of the Plac NC group were significantly reduced by 3.8%
      in the femur and 3.5% in the tibia compared to the contralateral limb. The
      percent diminution was reduced for OPG treated mice compared to the Plac NC group
      for both the femur and tibia. In the femur, the percent reduction of ipsilateral
      bone mass was reduced to 1.0% (LOW), 1.3% (MED) and 1.6% (HI) compared to the
      contralateral limb. In the tibia, loss of bone mass in the ipsilateral limb was
      reduced to 1.4% (LOW), 1.4% (MED), and 2.4% (HI) compared to the contralateral.
      OPG also decreased the amount of tibial endocortical resorption compared to the
      Plac NC group. In summary, OPG mitigated bone loss caused by damage to the
      sciatic nerve.

PMID- 11518256
TI  - The enhancement of periosteal chondrogenesis in organ culture by dynamic fluid
      pressure.
AB  - Cartilage repair by autologous periosteal arthroplasty is enhanced by continuous
      passive motion (CPM) of the joint after transplantation of the periosteal graft.
      However, the mechanisms by which CPM stimulate chondrogenesis are unknown. Based
      on the observation that an oscillating intra-synovial pressure fluctuation has
      been reported to occur during CPM (0.6-10 kPa), it was hypothesized that the
      oscillating pressure experienced by the periosteal graft as a result of CPM has a
      beneficial effect on the chondrogenic response of the graft. We have developed an
      in vitro model with which dynamic fluid pressures (DFP) that mimic those during
      CPM can be applied to periosteal explants while they are cultured in agarose gel
      suspension. In this study periosteal explants were treated with or without DFP
      during suspension culture in agarose, which is conducive to chondrogenesis.
      Different DFP application times (30 min, 4 h, 24 h/day) and pressure magnitudes
      (13, 103 kPa or stepwise 13 to 54 to 103 kPa) were compared for their effects on
      periosteal chondrogenesis. Low levels of DFP (13 kPa at 0.3 Hz) significantly
      enhanced chondrogenesis over controls (34 +/- 7% vs 14 +/- 5%; P < 0.05), while
      higher pressures (103 kPa at 0.3 Hz) completely inhibited chondrogenesis, as
      determined from the percentage of tissue that was determined to be cartilage by
      histomorphometry. Application of low levels of DFP to periosteal explants also
      resulted in significantly increased concentrations of Collagen Type II protein
      (43 +/- 8% vs 10 +/- 5%; P < 0.05). New proteoglycan synthesis, as measured by
      35S-sulphate uptake was increased by 30% in periosteal explants stimulated with
      DFP (350 +/- 50 DPM vs 250 +/- 75 DPM of 35S-sulphate uptake/microg total
      protein), when compared to controls though this difference was not statistically
      significant. The DFP effect at low levels was dose-dependant for time of
      application as well, with 4 h/day stimulation causing significantly higher
      chondrogenesis than just 30 min/day (34 +/- 7 vs 12 +/- 4% cartilage; P < 0.05)
      and not significantly less than that obtained with 24 h/day of DFP (48 +/- 9%
      cartilage, P > 0.05). These observations may partially explain the beneficial
      effect on cartilage repair by CPM. They also validate an in vitro model
      permitting studies aimed at elucidating the mechanisms of action of mechanical
      factors regulating chondrogenesis. The fact that these tissues were successfully
      cultured in a mechanical environment for six weeks makes it possible to study the
      actions of mechanical factors on the entire chondrogenic pathway, from induction
      to maturation. Finally, these data support the theoretical predictions regarding
      the role of hydrostatic compression in fracture healing.

PMID- 11518257
TI  - Alteration of fracture stability influences chondrogenesis, osteogenesis and
      immigration of macrophages.
AB  - Mechanical conditions at the fracture line determine the mode of fracture healing
      (osteonal versus non-osteonal bone union). The aim of this study was to
      investigate the influence of differing degrees of fracture stability on the time
      course of chondrogenesis, enchondral ossification and immigration of macrophages
      into the fracture callus. Using a fracture model of the rat's tibia, histological
      (Azan staining), immunohistological (antibodies directed against the macrophage
      specific surface antigen ED2), and molecular biological techniques (expression of
      the mRNA of the cartilage-specific collagen IX, osteocalcin - a marker for mature
      osteoblasts - and the macrophage-specific macrosialin) were employed. In terms of
      histology and molecular biology (collagen IX mRNA expression) chondrogenesis in
      the fracture gap continued for longer in less stable fractures. In more stable
      fractures bone formation - identified by osteocalcin mRNA expression - increased
      from day 12 onwards. The expression of the macrophage-specific surface antigen
      ED2 and the mRNA of macrosialin was more pronounced but of shorter duration in
      the more stable fractures. This study shows that differing degrees of fracture
      stability not only influence the interplay between osteogenesis and
      chondrogenesis but also alter the kinetics of macrophage immigration into the
      fracture callus. These findings could aid in better understanding the
      cytobiologic mechanisms of callus formation and may suggest that macrophages are
      an important factor not only in soft tissue healing but also in bone healing.

PMID- 11518258
TI  - Effect of force direction on femoral fracture load for two types of loading
      conditions.
AB  - Identifying the loading conditions under which the femur is most likely to
      fracture may aid the prevention of hip fracture. This study quantified the effect
      of force direction on fracture load, a factor inherently associated with fracture
      risk. Finite element (FE) models of four femora were used to determine the force
      directions associated with the lowest fracture loads. Force directions were
      varied three-dimensionally for two types of loading, one representing impact from
      a fall and one similar to joint loading during daily activities (atraumatic
      loading). For the fall configuration, the force direction with lowest fracture
      load corresponded to an impact onto the posterolateral aspect of the greater
      trochanter. For atraumatic loading, the lowest fracture loads for the force
      directions analyzed occurred when posterior force components were relatively
      large or when posterior and lateral components were both small, similar to
      conditions while standing on one leg or climbing stairs. When both fall and
      atraumatic configurations are considered, the type of loading associated with
      greatest fracture risk, i.e., with the greatest applied force and lowest fracture
      load, is impact from a fall onto the posterolateral aspect of the greater
      trochanter. Therefore, evaluation of hip fracture risk and development of
      fracture prevention technologies should focus on this high-risk loading
      condition.

PMID- 11518259
TI  - An expandable anchor for fixation in osteoporotic bone.
AB  - With the aging population, osteoporosis and osteoporotic fractures are becoming
      more prevalent. Adequate screw fixation in this type of bone is difficult. Screws
      are often cemented in bone to help obtain purchase. However, cement augmentation
      is not without problems. Here we present an expandable anchor for fixation in
      osteoporotic bone that does not require cement. We compared the ultimate holding
      power of this expandable anchor to a standard solid screw of similar dimensions.
      The solid screw and the expandable anchor were both placed into fresh frozen
      lumbar vertebral bodies and pulled out using a mechanical testing system. The
      expandable anchor had a 74% greater holding power compared to the standard screw
      (P = 0.02). The expandable anchor provides a significant increase in holding
      power without the problems associated with cement. This prototype anchor is
      promising for fixation in osteoporotic bone and warrants further evaluation.

PMID- 11518260
TI  - Prediction of mechanical properties of healing fractures using acoustic emission.
AB  - The objective of this study was to develop a non-destructive method for
      monitoring fracture healing with acoustic emission (AE). Experimentally produced
      fractures of the rat femur were tested in tension and in torsion at 4, 6, 8 and
      12 weeks after fracture. AE signals were monitored during these mechanical tests.
      The values for load and torque at the initiation of the AE signal were defined as
      new mechanical parameters. The apparent density and ash density of the fracture
      site were also measured at each time period. Tensile strength, tensile stiffness,
      maximum torque and torsional stiffness of the fracture site increased with time.
      The AE signal was detected before complete specimen failure. Load and torque for
      initiation of AE increased proportionally with increasing mechanical properties.
      The mineral density, however, reached a plateau at 8 weeks, when callus
      mechanical strength was approximately 50% of control. Load for initiation of AE
      was strongly correlated with the strength (r = 0.98), stiffness (r = 0.88), and
      failure strain (r = -0.63) of the callus. Torque for initiation of AE was highly
      correlated with the maximum torque (r = 0.95) and torsional stiffness (r= 0.93)
      of the callus. The findings of the present study indicated that some mechanical
      properties of healing fractures could be estimated by monitoring AE signals.

PMID- 11518262
TI  - Viability of ischemia/reperfused muscles in rat: a new evaluation method by RNA
      degradation.
AB  - The rat's skeletal muscle viability was evaluated using the muscle viability
      index (MVI) which reflects the mRNA degradation. To evaluate ischemic injury of
      the muscle, 24 hind limbs of Fischer rats (three subgroups of eight rats each)
      were preserved at normothermia for 1, 3 and 6 h and then tibialis anterior muscle
      was harvested. To investigate ischemia/reperfusion injury, another 48 limbs were
      transplanted to recipient Fischer rats after the ischemia at normothermia for 1,
      3 and 6 h, respectively. The transplanted muscles were harvested on day 3 and day
      7 after transplantation. Eight fresh muscles were also harvested and used as
      control. Total RNA isolated from each muscle was fractionated by electrophoresis
      and hybridized with 32P-labelled cDNA of GAPDH, and the radioactivity of intact
      and degraded GAPDH mRNA was measured. MVI was calculated as follows, MVI = [X/(X
      + Y)] x 100, where X and Y represent the radioactivities corresponding to intact
      GAPDH and degraded GAPDH mRNA band, respectively. In 1-h ischemia group, the MVI
      indices of both ischemic insult and ischemia/reperfusion group were comparable to
      control. In the 3-h ischemia group, the index of ischemia/reperfused group was
      comparable to control although the index of ischemic insult group was
      significantly lower than control. However, in the 6-h ischemia group, both
      indices of ischemic insult and ischemia/reperfusion group were significantly
      lower than control. These results show that the muscle damage was detected in
      ischemia at normothermia even after 3 h. However, this damage was overcome by
      reperfusion. There was no recovery from damage in muscles that had been preserved
      for more than 6 h which had resulted in irreversible degeneration. Therefore, in
      clinical muscle transplantation, one has to transplant the muscle at least within
      3-h ischemia.

PMID- 11518261
TI  - Pamidronate decreases tumor-induced osteoclastogenesis in osteopetrotic mice.
AB  - Recent studies indicate that the bisphosphonate pamidronate reduces skeletal
      complications caused by tumor osteolysis. In this investigation, the cellular
      mechanism through which pamidronate affects tumor-induced osteoclastogenesis is
      studied in osteopetrotic mice. A unique animal model is employed which studies
      the effect of pamidronate on a tumor (2472 sarcoma) which induces
      osteoclastogenesis in osteoclast-deficient mice (oplop). This model provides
      opportunity to specifically study effects on osteoclast formation and findings
      suggest that pamidronate decreases the number of osteoclasts at sites of 2472
      tumor by decreasing the number of osteoclast precursor cells at the level of
      myeloid precursors.

PMID- 11518263
TI  - Analysis of changes in mRNA levels of myoblast- and fibroblast-derived gene
      products in healing skeletal muscle using quantitative reverse transcription
      polymerase chain reaction.
AB  - Changes in expression of type III alpha1-collagen and myosin II heavy chains were
      characterized in rabbit skeletal muscle following single stretch injury using
      quantitative reverse transcription-polymerase chain reaction. Collagen III
      expression was highly elevated in the injured leg compared with the control limb
      both at the myotendinous junction and in the distal muscle belly. While
      upregulation of collagen III expression at the myotendinous junction was maximal
      on day 1, collagen III expression in the distal muscle belly was unchanged on day
      1 but highly elevated by day 3. Over the initial 7-day period, there was on
      average a 94% increase in collagen III expression at the myotendinous junction
      and a 42% increase in the distal muscle belly. On the other hand, there was
      little difference, in fact, slightly less expression of myosin II isoforms, in
      the injured leg compared with the control side. Immunohistochemical analysis of
      injured muscle showed significant collagen III deposition at the myotendinous
      junction beginning at day 3 post-injury and still evident by day 14. Focal
      deposits of type I and III collagen were first apparent in the distal muscle
      belly by day 3 and striking by day 7. Taken together, the data suggest the
      formation of connective tissue scar at the injury site and the absence of
      significant muscle regeneration following muscle stretch. Furthermore,
      microinjuries distant to the primary site of injury may result in more general
      muscle fibrosis and scarring.

PMID- 11518265
TI  - Gliding characteristics of tendon repair in canine flexor digitorum profundus
      tendons.
AB  - The gliding resistance between the flexor digitorum profundus (FDP) tendon and
      the proximal pulley system was measured using the method of S. Uchiyama, J.H.
      Coert, L. Berglund, P.C. Amadio, K.N. An (J. Orthop. Res. 13 (1995) 83) in 108
      adult dog digits in vitro. The FDP tendons were then lacerated to 80% of their
      transverse section. Each tendon was repaired with one of the following six suture
      techniques: Kessler, modified Kessler, Savage, Lee, Becker and simple running
      suture alone. Each repaired tendon was then tested again using the same method.
      The Student-Newman-Keuls test for multiple comparisons was performed for
      statistical analysis. The average gliding resistances of the Kessler, Savage, and
      Becker repairs were significantly greater than the resistances of the Lee,
      modified Kessler, and running suture alone repairs (P < 0.05). The Lee suture
      technique had a significantly greater resistance than the modified Kessler repair
      and the running suture (P < 0.05). The results of the peak gliding resistance
      followed the same trends, except that the modified Kessler repair was
      significantly higher than the running suture alone (P < 0.05). Suture techniques
      with a multi-strand core suture, with knots located outside the tendon surface,
      and with multiple-loops on the tendon surface may result in increased gliding
      resistance between the tendon and pulley system after tendon repair.

PMID- 11518264
TI  - Biochemical markers in the synovial fluid of glenohumeral joints from patients
      with rotator cuff tear.
AB  - It is known that rotator cuff tears are sometimes accompanied by joint
      destruction. Our purpose was to elucidate the pathology with this condition.
      Thirty-two synovial fluid (SF) samples aspirated from the glenohumeral joints of
      patients with rotator cuff tears, including 7 with partial-thickness and 25 with
      full-thickness tears of the rotator cuff (10 massive and 15 isolated
      supraspinatus tendon (SSp) tears), were examined. Collagenase (MMP-1),
      stromelysin 1 (MMP-3), tissue inhibitor of metalloproteinases-1 (TIMP-1) and
      carboxy-terminal type II procollagen peptide (pCOL Il-C) were measured in the SF
      using the respective sandwich enzyme immunoassays. Glycosaminoglycan (GAG) was
      also quantified with a cationic dye binding method using 1,9-dimethylmethylene
      blue. Levels of any molecules except pCOL II-C in the SF appeared to be higher in
      full-thickness tears than those in partial-thickness tears. Moreover, levels of
      MMP-1, MMP-3 and GAG in the SF were significantly higher in massive tears of the
      rotator cuff in comparison with those in isolated SSp tears. Such significance
      was not observed in the levels of TIMP-1 or pCOL II C in the SF. We examined the
      relation of those levels with operative findings or clinical parameters from full
      thickness tears, and observed significant correlations of the tear size with the
      levels of MMP-1, MMP-3 and GAG in the SF. Although these marker molecules in SF
      do not always originate from cartilage, our results may indicate the potential
      for accelerated cartilage-degrading activity in the glenohumeral joint in massive
      tears of the rotator cuff.

PMID- 11518266
TI  - The effects of partial and total interosseous membrane transection on load
      sharing in the cadaver forearm.
AB  - This study was performed to examine the effects of partial and total transection
      of the interosseous membrane (IOM) on load transfer in the forearm. Twenty fresh
      frozen forearms were instrumented with custom designed load cells placed in the
      proximal radius and distal ulna. Simultaneous measurements of load cell forces,
      radial head displacement relative to the capitellum, and local tension within the
      central band of the IOM were made as the wrist was loaded to 134 N with the
      forearm at 90 degrees of elbow flexion and in neutral pronation supination. For
      valgus elbow alignment (radial head contacting the capitellum), mean force
      carried by the distal ulna was 7.1% of the applied wrist force and mean force
      transferred from radius to ulna through the IOM was 4.4%. For varus elbow
      alignment (mean 2.0 mm gap between the radial head and capitellum), mean distal
      ulna force was 28% and mean IOM force was 51%. Section of the proximal and distal
      one-thirds of the IOM had no significant effect upon mean distal ulnar force or
      mean IOM force. Total IOM section significantly increased mean distal ulnar force
      for varus elbow alignment in all wrist positions tested. The mean level of
      applied wrist force necessary to close the varus gap (89 N) decreased
      significantly after both partial IOM section (71 N) and total IOM section (25 N).
      The IOM became loaded only when the radius displaced proximally relative to the
      ulna, closing the gap between the radius and capitellum. As the radius displaced
      proximally, the wrist becomes increasingly ulnar positive, which in turn leads to
      direct loading of the distal ulna. This shift of force to the distal ulna could
      present clinically as ulnar sided wrist pain or as ulnar impaction after IOM
      injury.

PMID- 11518267
TI  - Immunohistochemical demonstration of nerve fibers in the synovial fold of the
      human cervical facet joint.
AB  - The role of the intra-articular synovial fold as a source of facet joint pain is
      unclear, because the nature of nociceptive innervation in lumbar synovial folds
      is controversial, and there have been no such studies in cervical synovial folds.
      The present study aimed to demonstrate the presence of nerve fibers including
      nociceptive fibers in synovial folds of human cervical facet joints using
      immunohistochemistry. Synovial folds of cervical facet joints removed from
      patients undergoing cervical spine laminoplasty were analyzed
      immunohistochemically using antibodies to protein gene product 9.5, beta III
      tubulin, substance P and calcitonin gene-related peptide. Many nerve fibers
      immunoreactive for protein gene product 9.5 and beta III-tubulin were
      demonstrated both around blood vessels and as free fibers in the stroma of the
      synovial fold. Also. immunostaining showed the presence of free nerve fibers
      immunoreactive for substance P and calcitonin gene-related peptide in the stroma.
      The presence of putative nociceptive fibers in cervical synovial folds supports a
      possible role for these structures as a source of cervical facet joint pain.

PMID- 11518268
TI  - Regional variations in certain cellular characteristics in human lumbar
      intervertebral discs, including the presence of alpha-smooth muscle actin.
AB  - An evaluation of the regional variation of certain cellular features in the human
      intervertebral disc (IVD) could lead to a better understanding of site-specific
      properties relative to degradation, response to injury, and healing processes.
      The objective of this study was to determine how cell density, cell morphology,
      cell grouping, and expression of a specific actin isoform varied with location
      and degeneration in the human disc. A total of 41 human L4-L5 and L5-S1 discs
      removed postmortem from 21 individuals were analyzed. The discs were graded for
      degeneration based on the Thompson scale and processed for evaluation. Microtomed
      sections from paraffin-embedded specimens were stained with hematoxylin and eosin
      or a monoclonal antibody to alpha-smooth muscle actin (alpha-SMA), an actin
      isoform often associated with contraction. A significant regional dependence was
      found for most of the measured parameters. A fourfold increase in cell density
      was found in proceeding from the nucleus pulposus (NP) to the outer annulus (OA)
      of the IVD. Approximately 30% of the cells in the NP were present in groups.
      Virtually all of the cells in the NP and 40% of those in the OA were round.
      Moreover, notable percentages (12-15%) of the cells in the NP and inner annulus
      (IA) contained alpha-SMA. Only pair density was found to be correlated with
      Thompson grade, with more degenerated specimens having higher values. A greater
      effect was also observed on the percentage of cells in groups. These findings
      provide the basis for future work to investigate the importance of cells in
      groups, the role of alpha-SMA in the disc, and the changes in these cellular
      characteristics in pathological disc conditions.

PMID- 11518269
TI  - A new rabbit model for the study on cervical compressive myelopathy.
AB  - Development process and pathology of myelopathy due to chronic spinal cord
      compression have not been fully elucidated. This study was conducted in order to
      establish an experimental model which can efficiently produce myelopathy and be
      useful in the studies on myelopathy due to chronic spinal cord compression. Under
      electrophysiological monitoring of the spinal cord, anterior compression was
      produced on C5 using a plastic screw. Two weeks later, a plastic plate was
      inserted under the C5 arch. For the subsequent 10 months on average, walking
      pattern and MR images were periodically monitored. Before the sacrifice,
      electrophysiological test was performed and then histopathological examination
      was done. Palsy appeared at 5 months on average after the addition of posterior
      compression. Mean compression ratio of the spinal cord calculated on MR images
      was 34%. All animals with compression showed a high intramedullary signal
      intensity, and the mean contrast-to-noise ratio (CNR) in the compressed area was
      49%. Electrophysiological test showed a significant decrease in the amplitude of
      spinal cord evoked potentials (SCEPs) at the given compression level. Histology
      showed flattening of the anterior horn, disappearance and necrosis of anterior
      horn cells in the gray matter; and demyelination and axonal degeneration in the
      white matter. The antero-posterior compression produces the condition of spinal
      canal stenosis. Repeated antero-posterior compression to the spinal cord is
      important in establishing myelopathy. The present animal model was evaluated to
      be useful in the studies on myelopathy.

PMID- 11518270
TI  - The effect of component placement on knee kinetics after arthroplasty with an
      unconstrained prosthesis.
AB  - The mechanical success of a total knee replacement demands stable patellar
      tracking without subluxation and, stable tracking, in turn, can depend largely on
      the medial-lateral forces restraining the patella. Patellar button medialization
      has been advocated as a means of reducing subluxation, and experimental evidence
      has shown femoral component rotation also affects medial-lateral forces. Surgeons
      have choices in femoral component rotation and patellar button medialization and
      must frequently make intra-operative decisions concerning component placement
      because of anatomical variations among patients. Thus, in seeking to minimize
      medial-lateral patellar force, we examined the effects of patellar button
      medialization and external femoral component rotation. The study used an
      unconstrained total knee system implanted in nine cadaveric specimens tested on a
      knee simulator operating through flexion angles up to 100 degrees. Tests included
      all combinations of external femoral component rotation of 0 degree, 2.5 degrees,
      and 5 degrees and patellar placement at the geometric center and at 3.75 mm
      medial to the geometric center. A video-based motion analysis system tracked
      patellar and tibial kinematics while a six-component load cell measured
      patellofemoral loads. Repeated measures analysis of variance revealed a
      statistically significant decrease in the average medial-lateral force with
      button medialization but no significant change with femoral component rotation.
      Neither femoral component rotation nor patellar button medialization had an
      effect on the normal component of the patellar reaction force. External femoral
      component rotation did cause significant increases in lateral patellar tilt, in
      tibial varus angle, and in external tibial rotation. Button medialization caused
      significant increases in lateral patellar tracking, lateral patellar tilt and
      external tibial rotation. The results in medial-lateral patellar forces quantify
      the benefit of patellar button medialization and discount any benefit of femoral
      rotation. The change in tibial kinematics with patellar button medialization and
      femoral component rotation cannot be measured in vivo with current technology,
      and the precise clinical implications are unknown.

PMID- 11518271
TI  - Effects of hydroxyapatite particulate debris on the production of cytokines and
      proteases in human fibroblasts.
AB  - Cytokines and proteases are secreted by fibroblasts in response to particulate
      wear debris, and these proteins are felt to play an important role in the
      development of osteolysis and implant loosening. Although metallic and
      polyethlyene debris have been studied extensively, little is known about the
      cellular responses to hydroxyapatite, despite the wide clinical use of these
      materials. Therefore, the effects of hydroxyapatite (HA) and hydroxyapatite/beta
      tricalciumphosphate (HA/TCP) on cellular proliferation, cytokine gene expression
      and protein secretion, protease synthesis, and gelatinolytic activity were
      investigated in human fibroblasts. HA and HA/TCP particles were synthesized, and
      their effects were compared to the responses elicited by titanium and cobalt
      chromium. Sample characterization by scanning electron microscopy and Coulter
      Counter demonstrated that the materials had a mean particle size of less than 10
      microm, and all of the particles were compared using the same concentration
      ranges. Aliquots of particle suspensions were added to human fibroblasts
      maintained in tissue culture, and dose-response and time-course experiments were
      performed. Effects of the particles on fibroblast proliferation were assessed,
      and alterations in cytokine levels were determined by specific enzyme linked
      immunosorbent assays (ELISA). Cytokines that were evaluated included interleukin
      1 (IL-1beta), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha),
      all of which have been demonstrated to enhance bone resorption and are associated
      with osteolysis and implant loosening. Gene expression was determined using
      Northern blot analysis with cytokine-specific probes, while secretion of the
      proteases collagenase and stromelysin was determined by Western blot analysis.
      Functional gelatinolytic assay was assessed using zymogram gels. The particles
      were evaluated in a concentration range from 0.000021 to 0.021 vol%. All of the
      particles produced increases in cellular proliferation up to 0.0021 vol%, with
      the largest increases being seen at 0.021 vol% with HA/TCP and titanium. At the
      highest concentration, both cobalt chromium and HA samples decreased cellular
      proliferation relative to lower doses, possibly representing cytotoxicity.
      Hydroxyapatite particles yielded a 30-fold increase in interleukin-6 secretion
      compared to unstimulated controls, which was also greater than three times the
      levels produced by cobalt chromium, titanium, or HA/TCP. HA particles also
      tripled the secretion of IL-1beta at 0.00021 vol%, and doubled TNF-alpha
      secretion at 0.021 vol%. Addition of conditioned media prepared by incubation of
      the particles in culture medium in the absence of cells did not alter the
      secretion of any of the cytokines. Northern blot analysis using IL-6 probes also
      demonstrated strong increases with HA compared to the other materials, suggesting
      that the action of the HA particles was at the level of transcription. Secretion
      of the protease collagenase was increased by all of the samples including HA when
      compared to unstimulated controls. Stromelysin secretion into the culture medium
      was decreased by cobalt chromium, but increased by titanium, HA, and HA/TCP. All
      of the particles including HA increased the gelatinolytic activity of the
      fibroblasts. These findings demonstrate that HA and HA/TCP particles are capable
      of stimulating the expression and secretion of cytokines and proteases that
      enhance bone resorption, and suggest that particulate debris from implants using
      these coatings may also increase osteolysis and loosening.

PMID- 11518272
TI  - Quadriceps protects the anterior cruciate ligament.
AB  - The aim of this study is to show that the quadriceps is the primary muscular
      restraint to anterior tibial translation during closed kinetic chain activities
      such as running, jumping, walking, and standing. It is my hypothesis that the
      quadriceps vector is directed superiorly during open kinetic chain knee extension
      and inferiorly during closed kinetic chain knee extension. My methods involve
      vector analysis based on a lateral radiograph of the normal human knee and muscle
      ultrasound. My results show that the quadriceps vector is directed superiorly for
      open kinetic chain knee extension and inferiorly for closed kinetic chain knee
      extension. The inferiorly directed quadriceps vector has an anterior femoral
      tibial or posterior tibial-femoral component, which protects the anterior
      cruciate ligament (ACL) from anterior tibial-femoral shear. Therefore during
      closed kinetic chain activities, the quadriceps protects the ACL regardless of
      the activity of the hamstrings. Given that the quadriceps is much stronger than
      the hamstrings, has better leverage at low knee flexion angles, and a favorable
      vector with regard to the ACL during closed kinetic chain activities, and since
      most activities of daily living, sports, and non-contact ACL injuries occur with
      the foot on the ground, then it can be concluded that the quadriceps is the
      primary ACL protagonist. My findings have the following implications: (1) weak
      quadriceps are a risk factor for non-contact ACL injuries, (2) strong quadriceps
      are important for ACL injury prevention and rehabilitation, and (3) preservation
      of quadriceps strength is an important surgical goal.

PMID- 11518273
TI  - Tissue distribution and measurement of cartilage oligomeric matrix protein in
      patients with magnetic resonance imaging-detected bone bruises after acute
      anterior cruciate ligament tears.
AB  - Histologic and immunostaining analyses were performed on articular
      cartilage/subchondral bone biopsy specimens overlying MRI-detected bone bruises
      in 12 patients with anterior cruciate ligament (ACL) tears. Staining with
      toluidine blue for proteoglycan revealed loss of staining from the superficial
      portion of the articular cartilage. Immunostaining for cartilage oligomeric
      matrix protein (COMP) showed an increased staining in the superficial matrix of
      the articular cartilage. Using polyclonal antisera against COMP, the authors
      performed a competitive enzyme-linked immunosorbent assay (ELISA) on the synovial
      fluid from the injured and uninjured knees. There was an approximately 10-fold
      higher synovial fluid COMP levels in injured knees. The COMP levels were greater
      in those patients who had synovial fluid samples harvested closer to the date of
      initial injury. Western blot analysis of the synovial fluid showed an increased
      presence of COMP degradation fragments from injured knees. These results are
      indicative of a significant injury to the articular cartilage, and may represent
      preclinical posttraumatic osteoarthritic lesions.

PMID- 11518274
TI  - Expression of matrix metalloprotease and tissue inhibitor of metalloprotease
      genes in human anterior cruciate ligament.
AB  - Women are more susceptible to anterior cruciate ligament (ACL) injuries than men
      performing similar athletic activities. Because tissue remodeling may affect
      ligament strength, we assessed expression of tissue remodeling effector genes in
      the human ACL. Specifically, we surveyed ACL for RNAs encoding all known matrix
      metalloproteases (MMPs) and tissue inhibitors of metalloproteases (TIMPs) by
      reverse transcription/polymerase chain reaction (RT-PCR). These experiments
      revealed that mRNAs encoding nine of sixteen MMPs and all four TIMPs are present
      in the normal ACL. The nine expressed proteases were MMPs 1-3, 7, 9, 11, 14, and
      17 (collagenase 1, gelatinase A, stromelysin 1, matrilysin, gelatinase B,
      stromelysin 3, and membrane types 1 and 4, respectively), and MMP-18. Genes for
      MMPs 8, 10, 12, 13, 15, and 16 appeared not to be expressed in ACL, as their
      mRNAs were not detected using RT-PCR conditions that did yield positive signals
      from other tissues (testis or bone). We conclude that numerous genes encoding
      tissue remodeling effector proteins are expressedin the human ACL.

PMID- 11518275
TI  - Absolute concentrations of mRNA for type I and type VI collagen in the canine
      meniscus in normal and ACL-deficient knee joints obtained by RNase protection
      assay.
AB  - Relatively little is known about the cellular and molecular responses of the knee
      joint meniscus to joint injury, despite the functional importance of the tissue.
      We investigated how meniscus cells respond to joint injury in the early stages of
      post-traumatic osteoarthritis by characterizing the changes in matrix gene
      expression in menisci at 3 and 12 weeks post-surgery in dogs in which the
      anterior cruciate ligament (ACL) in one joint was transected and the other
      unoperated joint served as a control. Changes in the total RNA and DNA
      concentrations of the menisci were determined. Absolute concentrations of the
      mRNA of the COL1A1 gene of type 1 collagen, the major fibrillar collagen of the
      meniscus, and the COL6A3 gene of type VI collagen, a major repair molecule, were
      determined by quantitative ribonuclease (RNase) protection assay. The
      concentration of total RNA in medial and lateral menisci increased from 40 to 60
      microg RNA/g wet wt in unoperated, control joints to 200-350 microg RNA/g wet wt
      in ACL-deficient joints. No significant changes were detected in the
      concentration of DNA (900-1200 microg DNA/g wet wt). Low concentrations of COL1A1
      (2-3 pmol mRNA/g DNA) and COL6A3 (0.3-0.6 pmol mRNA/g DNA) mRNA transcripts were
      measured in normal menisci. ACL-deficiency induced a 20-38 fold increase in
      COL1A1 and COL6A3 mRNA concentration at 3 weeks, and an 11-19 fold increase at 12
      weeks post-surgery. In general, the increase in COL1A1 and COL6A3 mRNA
      concentrations was greater in medial menisci than in lateral menisci. These
      results demonstrate that the menisci initiate a vigorous biosynthetic response to
      transection of the ACL.

PMID- 11518276
TI  - Distribution of smooth muscle actin-containing cells in the human meniscus.
AB  - This is the first report of a contractile actin isoform, a-smooth muscle actin
      (SMA), in the cells of the human meniscus that lacked meniscal tears based on
      gross anatomical appearance. Approximately 25% of the cells in the tissue
      contained SMA by immunohistochemistry. Most of the SMA-positive cells were
      chondrocytic in morphology.

PMID- 11518277
TI  - The effect of tibial lengthening using the Ilizarov method on the cartilage and
      the menisci of the knee joint.
AB  - In order to investigate possible acute damage to the knee joint cartilage and the
      menisci during tibial lengthening, sixteen young beagle dogs underwent 30%
      lengthening of the right tibia of 2.5 cm by callus distraction at a distraction
      rate of twice 0.5 mm per day. A further four dogs comprised the control group
      with fixator and osteotomy but without lengthening. After a distraction period of
      25 days half the dogs were killed (group A) while the other half (eight dogs with
      limb lengthening and two dogs without) were killed after a further period of 25
      days (group B). At the end of the study, the menisci were removed together with
      three cartilage-bone cylinders from both femoral condyles from the weight-bearing
      zones as well as from the corresponding tibial condyles. Serial sections from the
      menisci were stained with haematoxylin and eosin (H&E) and Elastica van Gieson.
      Sections of the cartilage-bone cylinders were stained with H&E and safranin-O.
      Cartilage thickness was measured and the glycosaminoglycan content of the joint
      cartilage was determined using microspectrophotometry. None of the histological
      preparations obtained from the untreated and distracted sides showed any signs of
      damage to the cartilage or to the menisci. There were no significant differences
      between cartilage thickness and proteoglycan content of the untreated side and
      the lengthened side. Thus, tibial lengthening using the llizarov method does not
      appear to cause acute damage to the cartilage of the knee joint or to the
      menisci.

PMID- 11518278
TI  - Phospholipid composition of articular cartilage boundary lubricant.
AB  - The mechanism of lubrication in normal human joints depends on loading and
      velocity conditions. Boundary lubrication, a mechanism in which layers of
      molecules separate opposing surfaces, occurs under severe loading. This study was
      aimed at characterizing the phospholipid composition of the adsorbed molecular
      layer on the surface of normal cartilage that performs as a boundary lubricant.
      The different types of phospholipid adsorbed onto the surface of cartilage were
      isolated by extraction and identified by chromatography on silica gel paper and
      mass spectroscopy. The main phospholipid classes identified were quantified by a
      phosphate assay. Gas chromatography and electrospray ionization mass spectrometry
      were used to further characterize the fatty acyl chains in each major
      phospholipid component and to identify the molecular species present.
      Phosphatidylcholine (41%), phosphatidylethanolamine (27%) and sphingomyelin (32%)
      were the major components of the lipid layer on the normal cartilage surface. For
      each lipid type, a mixture of fatty acids was detected, with a higher percentage
      of unsaturated species compared to saturated species. The most abundant fatty
      acid observed with all three lipid types was oleic acid (C18:1). Additional work
      to further quantify the molecular species using electrospray ionization mass
      spectrometry is recommended.

PMID- 11518279
TI  - Homology of lubricin and superficial zone protein (SZP): products of
      megakaryocyte stimulating factor (MSF) gene expression by human synovial
      fibroblasts and articular chondrocytes localized to chromosome 1q25.
AB  - We have previously identified megakaryocyte stimulating factor (MSF) gene
      expression by synovial fibroblasts as the origin of lubricin in the synovial
      cavity. Lubricin is a mucinous glycoprotein responsible for the boundary
      lubrication of articular cartilage. MSF has a significant homology to vitronectin
      and is composed of 12 exons. RNA was purified from human synovial fibroblasts and
      articular chondrocytes grown in vitro from tissue explants obtained from subjects
      without degenerative joint disease. RT-PCR was used with multiple complimentary
      primer pairs spanning the central mucin expressing exon 6 of the MSF gene and
      individual exons on both the N- and C-terminal sides of exon 6. Exons 2, 4 and 5
      appear to be variably expressed by synovial fibroblasts and articular
      chondrocytes. Lubricating mucin, in the form of MSF, is expressed by both
      chondrocytes and synovial fibroblasts in vitro. Both lubricin and superficial
      zone protein (SZP), a related proteoglycan, share a similar primary structure but
      could differ in post-translational modifications with O-linked oligosaccharides
      which are predominant in lubricin and with limited amounts chondroitin and
      keratan sulfate found in SZP. Since most of the MSF exons are involved in the
      expression of lubricating mucin, a strong homology to vitronectin persists. It is
      therefore appropriate to consider that both SZP and lubricin occupy a new class
      of biomolecules termed tribonectins. Screening of a human genome bacterial
      artificial chromsome (BAC) library with a cDNA primer pair complimentary for exon
      6 identified two clones. Both clones were complimentary for chromosome 1q25 by in
      situ hybridization. This same locus was previously implicated in camptodactyl
      arthropathy-pericarditis syndrome (CAP) by genetic mapping. It is hypothesized
      that CAP, a large joint arthropathy, may be associated with ineffective boundary
      lubrication provided by synovial fluid.

PMID- 11518280
TI  - Corticosteroids alter the differentiated phenotype of articular chondrocytes.
AB  - Experimental evidence suggests that recommended dosages of some corticosteroids
      used clinically as antiinflammatory agents for treating arthropathies damage
      articular cartilage, but low dosages may be chondroprotective. The purpose of
      this study was to evaluate how different concentrations of methylprednisolone
      affect chondrocyte function and viability. Articular cartilage and chondrocytes
      were obtained from young adult horses, 1.5-3.5 years of age. Corticosteroid
      induced changes in collagen expression were studied at the transcriptional level
      by Northern blot analyses and at the translational level by measuring [3H]
      proline incorporation into [3H]-hydroxyproline. Fibronectin mRNA splicing
      patterns were evaluated with ribonuclease protection assays. Cytotoxicity was
      studied using erythrosin B dye exclusion. Steady-state levels of type II
      procollagen mRNA decreased without concurrent changes in type I procollagen
      expression as the medium methylprednisolone concentrations were increased from 1
      x 10(1) to 1 x 10(8) pg/ml, dropping below 10% of control values by 1 x 10(5)
      pg/ml. Cytotoxicity occurred as methylprednisolone levels were increased further
      from 1 x 10(8) to 1 x 10(9) pg/ml. Changes in total collagen (protein) synthesis
      were less pronounced, but also demonstrated significant suppression between 1 x
      10(4) and 1 x 10(8) pg/ml. Corticosteroid-induced changes in fibronectin isoform
      levels were evaluated in articular cartilage samples without in vitro culture.
      The cartilage-specific (V + C)(-) isoform was suppressed in both normal and
      inflamed joints by a single intraarticular injection (0.1 mg/kg) of
      methylprednisolone. Combined, these data indicate that methylprednisolone
      suppresses matrix protein markers of chondrocytic differentiation. Decreased and
      altered chondrocyte expression of matrix proteins likely contributes to the
      pathogenesis of corticosteroid-induced cartilage degeneration.

PMID- 11518281
TI  - Signal transduction pathways and apoptosis in bacteria infected chondrocytes.
AB  - The mechanism underlying chronic destructive arthropathy after pyogenic arthritis
      is not clear. This study evaluated the role of apoptosis in Staphylococcus aureus
      infected human articular chondrocytes and investigated the signal transduction
      pathways activated by bacterial infection. Chondrocytes cultured in monolayer
      were challenged with bacteria for 6 h and were analyzed after incubation for 2,
      18, and 24 h. Chondrocytes showed morphologic and biochemical evidences of
      apoptosis after infection and the following incubation period. Although treatment
      with extensive washing and vancomycin could ameliorate the amount of apoptosis
      from 31% to 15% at 2 h, from 48% to 23% at 18 h, and from 58% to 33% at 24 h, the
      infected samples with treatment still had higher amount of apoptosis than the un
      infected controls (ANOVA P < 0.001). Accompanying with the increasing amount of
      apoptosis, the caspase activity was upregulated in bacteria infected samples and
      remained high in samples with treatment (ANOVA P < 0.05). Signal transduction
      pathways activated by bacterial infection were assessed by co-transfection
      technique. After infection, the c-Jun N-terminal kinase, extracellular signal
      regulated kinase, and cyclic AMP-dependent protein kinase activities were
      elevated by 7.6-, 7.3-, and 3.2-fold, respectively, compared to the uninfected
      controls. The data support the hypothesis that human chondrocytes will undergo
      apoptosis after infection by a single organism. Apoptosis and activated
      intracellular kinase activities may be related to the pathogenesis of post
      infectious destructive arthropathy.

PMID- 11518282
TI  - Chondrocyte necrosis and apoptosis in impact damaged articular cartilage.
AB  - A decrease in chondrocyte numbers is one characteristic of osteoarthritic
      cartilage. This decrease may be the result of apoptosis or other forms of cell
      death induced by mechanical damage. Furthermore, cell death may contribute to the
      structural and metabolic changes found in osteoarthritic cartilage. Therefore, we
      investigated cell viability and the mode of cell death in cartilage subjected to
      an increasing severity of impact loads expected to cause compositional damage and
      osteoarthritic-like metabolic alterations. Canine cartilage explants were
      subjected to cyclic indentation impacts of 5 megapascals at 0.3 Hz for 0, 2, 20,
      and 120 min and then kept in culture for 2, 4, 48, and 144 h. Cell death was
      assessed by the TUNEL assay and by uptake of propidium iodide. Viable cells were
      detected by the ability to metabolize fluorescein diacetate. Nuclear morphology
      and ultrastructure of the cell were examined using Hoechst 33342 fluorescent
      staining and transmission electron microscopy (TEM). As controls for necrosis and
      apoptosis, cartilage was, respectively, frozen and thawed or incubated with
      mitomycin-C, an apoptosis inducer. In cartilage that had been loaded for 2 h, 32%
      of the chondrocytes in the loaded core took up propidium iodide within 2 h after
      loading. Most of these were in the middle to superficial zones and reflected
      leaky cell membranes usually characteristic of necrosis. Less than 1% of these
      chondrocytes were positive in the TUNEL assay after 4 h. After additional culture
      for 2 days, however, the proportion of chondrocytes which were positive in the
      TUNEL assay reached 73%. A dose dependent response to duration of loading was
      detected with the TUNEL assay at this time. The TUNEL assay was not specific for
      apoptosis since 92% of chondrocytes in freeze/thawed cartilage were TUNEL
      positive. However, some cells with apoptotic bodies and chromatin condensation
      characteristic of apoptosis were found in the transition zone between necrotic
      and normal chondrocytes, but not in the superficial and upper zones, in impact
      damaged cartilage. We concluded that in this study, necrosis occurred first,
      followed by apoptosis.

PMID- 11518283
TI  - Cytokine regulation of cartilage-derived retinoic acid-sensitive protein (CD-RAP)
      in primary articular chondrocytes: suppression by IL-1, bfGF, TGFbeta and
      stimulation by IGF-1.
AB  - Cartilage-derived retinoic acid-sensitive protein (CD-RAP) is a secreted protein
      identified in our laboratory by RT-PCR and differential display [U.H. Dietz, L.J.
      Sandell. Cloning of a retinoic acid-sensitive mDNA expressed in cartilage and
      during chondrogenesis. J. Biol. Chem. 271 (1996) 3311-3316]. It is synthesized by
      chondrocytes throughout development and down-regulated by retinoic acid in
      coordination with type II collagen gene expression. To further explore the
      regulation CD-RAP in primary articular chondrocytes, we examined effects of
      selected cytokines on CD-RAP gene expression compared to their effects on type II
      collagen expression. Northern blot analysis showed that expression of CD-RAP mRNA
      was suppressed by bFGF, IL-1beta and retinoic acid in coordination with type II
      collagen mRNA. TGF-beta decreased CD-RAP expression while increasing type II
      collagen mRNA whereas both mRNAs were up-regulated by IGF-1. In chondrocytes
      dedifferentiated with retinoic acid, IGF-1 induced re-expression of both CD-RAP
      and type II collagen mRNAs. The mechanism of stimulation of CD-RAP by IGF-1 was
      further investigated. An mRNA stability assay revealed that IGF-1 had no effect
      on CD-RAP or type II collagen mRNA half life, suggesting that the enhancement by
      IGF-1 is due to increased gene transcription. To study the transcriptional
      mechanism, we used the 5'-flanking region of the CD-RAP gene fused to a promoter
      less reporter plasmid encoding luciferase. Deletion analysis of the CD-RAP
      promoter indicated that an IGF-1-responsive element is present between
      nucleotides -475 and -458. These data indicate that CD-RAP expression can be
      regulated by cytokines known to influence chondrocyte metabolism and that IGF-1
      up-regulates CD-RAP gene expression through a transcriptional mechanism.

PMID- 11518284
TI  - Insulin-like growth factor-I gene expression patterns during spontaneous repair
      of acute articular cartilage injury.
AB  - This study evaluated the constitutive insulin-like growth factor-I (IGF-I) gene
      expression pattern in spontaneously healing cartilage defects over the course of
      16 weeks, and correlated the tissue morphology and matrix gene expression with
      IGF-I mRNA levels. Full-thickness 15 mm cartilage defects were debrided in the
      femoral trochlea of both femoropatellar joints of 8 horses and the healing
      defects examined 2, 4, 8, or 16 weeks after surgery. Samples were harvested for
      histologic assessment of tissue healing using H&E staining, toluidine blue
      histochemical reaction for proteoglycan deposition, and in situ hybridization and
      immunohistochemistry procedures to demonstrate collagen type II mRNA and protein
      expression. Total RNA was isolated for Northern analysis to measure cartilage
      matrix molecule expression, and for semi-quantitative reverse transcription
      polymerase chain reaction (RT-PCR) to determine IGF-I gene expression patterns in
      healing cartilage defects. Full-thickness cartilage defects in horses were slow
      to heal compared to smaller lesions in similar locations in other animals.
      However, a progressive decline in tissue cellularity and vascularity, and
      increased tissue organization were observed on H&E stained specimens over the 16
      week experiment. Evidence of early chondrogenic repair was detected through
      collagen type II in situ hybridization and immunohistochemistry. However, levels
      of collagen type II and aggrecan mRNA in lesions were not abundant on Northern
      analysis indicating incomplete chondrogenesis. IGF-I message expression followed
      a cyclic pattern with low levels at 2 weeks, followed by an increase at 4 and 8
      weeks, and a subsequent decline at 16 weeks. There was no direct correlation
      between the stage of healing and cartilage matrix message expression, and the
      abundance of IGF-I mRNA in the healing lesions. In conclusion, this study
      demonstrated that the spontaneous healing of articular defects was accompanied by
      a temporal fluctuation in IGF-I gene expression which was discoordinate to the
      steady rise in expression of cartilage matrix molecules such as procollagen type
      II.

PMID- 11518285
TI  - The effects of static and intermittent compression on nitric oxide production in
      articular cartilage explants.
AB  - Nitric oxide (NO) production and NO synthase (NOS) expression are increased in
      osteoarthritis and rheumatoid arthritis, suggesting that NO may play a role in
      the destruction of articular cartilage. To test the hypothesis that mechanical
      stress may increase NO production by chondrocytes, we measured the effects of
      physiological levels of static and intermittent compression on NOS activity, NO
      production, and NOS antigen expression by porcine articular cartilage explants.
      Static compression significantly increased NO production at 0.1 MPa stress for 24
      h (P < 0.05). Intermittent compression at 0.5 Hz for 6 h followed by 18 h
      recovery also increased NO production and NOS activity at 1.0 MPa stress (P <
      0.05). Intermittent compression at 0.5 Hz for 24 h at a magnitude of 0.1 or 0.5
      MPa caused an increase in NO production and NOS activity (P < 0.05). Immunoblot
      analysis showed stress-induced upregulation of NOS2, but not NOS1 or NOS3. There
      was no loss in cell viability following any of the loading regimens. Addition of
      2 mM 1400 W (a specific NOS2 inhibitor) reduced NO production by 51% with no loss
      of cell viability. These findings indicate that NO production by chondrocytes is
      influenced by mechanical compression in vitro and suggest that biomechanical
      factors may in part regulate NO production in vivo.

PMID- 11518286
TI  - Chondrocytic differentiation of mesenchymal stem cells sequentially exposed to
      transforming growth factor-beta1 in monolayer and insulin-like growth factor-I in
      a three-dimensional matrix.
AB  - This study evaluated chondrogenesis of mesenchymal progenitor stem cells (MSCs)
      cultured initially under pre-confluent monolayer conditions exposed to
      transforming growth factor-beta1 (TGF-beta1), and subsequently in three
      dimensional cultures containing insulin-like growth factor I (IGF-I). Bone marrow
      aspirates and chondrocytes were obtained from horses and cultured in monolayer
      with 0 or 5 ng of TGF-beta 1 per ml of medium for 6 days. TGF-beta 1 treated and
      untreated cultures were distributed to three-dimensional fibrin disks containing
      0 or 100 ng of IGF-I per ml of medium to establish four treatment groups. After
      13 days, cultures were assessed by toluidine blue staining, collagen types I and
      II in situ hybridization and immunohistochemistry, proteoglycan production by
      [35S]-sulfate incorporation, and disk DNA content by fluorometry. Mesenchymal
      cells in monolayer cultures treated with TGF-beta1 actively proliferated for the
      first 4 days, developed cellular rounding, and formed cell clusters. Treated MSC
      cultures had a two-fold increase in medium proteoglycan content. Pretreatment of
      MSCs with TGF-beta1 followed by exposure of cells to IGF-I in three-dimensional
      culture significantly increased the formation of markers of chondrocytic function
      including disk proteoglycan content and procollagen type II mRNA production.
      However, proteoglycan and procollagen type II production by MSC's remained lower
      than parallel chondrocyte cultures. MSC pretreatment with TGF-beta1 without
      sequential IGF-I was less effective in initiating expression of markers of
      chondrogenesis. This study indicates that although MSC differentiation was less
      than complete when compared to mature chondrocytes, chondrogenesis was observed
      in IGF-I supplemented cultures, particularly when used in concert with TGF-beta1
      pretreatment.

PMID- 11518287
TI  - Exposure to methyl tertiary butyl ether and benzene in close proximity to service
      stations.
AB  - Exposure estimates based solely on proximity to air pollution sources are not
      sound and require confirmation. Accordingly, since a very limited amount of
      actual data for this type of exposure estimate is currently available, this study
      was conducted to provide actual data on residents' exposure to two important
      gasoline constituents [methyl tertiary butyl ether (MTBE) and benzene] relative
      to their proximity to roadside service stations. The results confirmed that
      residents in neighborhoods near service stations are exposed to elevated ambient
      MTBE and benzene levels compared with those living farther from such a source.
      However, it was also found that the presumed elevated outdoor benzene levels (a
      mean of 1.7 ppb) even in close proximity to service stations did not exceed the
      indoor levels (a mean of 2.2 ppb) of exposure for those living nearby. Regardless
      of residents' distance from service stations, an indoor source (cigarette
      smoking) appeared to be the major contributor to their benzene exposure.
      Conversely, for MTBE, roadside service stations were found to be the major
      contributor to residents' exposure. In addition, the residents close to the
      stations were exposed to elevated indoor and outdoor MTBE levels. The sampling
      period (daytime and nighttime) and season (winter and summer) were additional
      parameters for the outdoor MTBE and benzene levels and the indoor MTBE levels.
      Meanwhile, the breathing zone air concentrations of service station attendants
      for both MTBE and benzene were significantly higher than those of drivers (p <
      0.05). In addition, the breathing zone concentrations were significantly higher
      during summer than during winter for both drivers and attendants (p < 0.05).

PMID- 11518288
TI  - Analysis of air toxics emission inventory: inhalation toxicity-based ranking.
AB  - Air toxics emission inventories play an important role in air quality regulatory
      activities. Recently, Minnesota Pollution Control Agency (MPCA) staff compiled a
      comprehensive air toxics emission inventory for 1996. While acquiring data on the
      mass of emissions is a necessary first step, equally important is developing
      information on the potential toxicity of the emitted pollutants. To account for
      the toxicity of the pollutants in the emission inventory, inhalation health
      benchmarks for acute effects, chronic effects, and cancer were used to weight the
      mass of emissions. The 1996 Minnesota emissions inventory results were ranked by
      mass of emissions and by an index comprised of emissions divided by health
      benchmarks. The results show that six of eight pollutants ranked highest by
      toxicity were also the pollutants of concern indicated in environmental
      monitoring data and modeling data. Monitoring data and modeling results did not
      show high impacts of the other two pollutants that were identified by the
      toxicity-based emission ranking method. The biggest limitation in this method is
      the lack of health benchmark values for many pollutants. Despite uncertainties
      and limited information, this analysis provides useful information for further
      targeting pollutants and source categories for control.

PMID- 11518289
TI  - Monitoring and source apportionment of particulate matter near a large phosphorus
      production facility.
AB  - A source apportionment study was conducted to identify sources within a large
      elemental phosphorus plant that contribute to exceedances of the National Ambient
      Air Quality Standards (NAAQS) for 24-hr PM10. Ambient data were collected at
      three monitoring sites from October 1996 through July 1999, and included the
      following: 24-hr PM10 mass, 24-hr PM2.5 and PM10-2.5 mass and chemistry,
      continuous PM10 and PM2.5 mass, continuous meteorological data, and wind
      direction-resolved PM2.5 and PM10 mass and chemistry. Ambient-based receptor
      modeling and wind-directional analysis were employed to help identify major
      sources or source locations and source contributions. Fine-fraction phosphate was
      the dominant species observed during PM10 exceedances, though in general,
      resuspended coarse dusts from raw and processed materials at the plant were also
      needed to create an exceedance. Major sources that were identified included the
      calciners, the CO flares, process-related dust, and electric-arc furnace
      operations.

PMID- 11518290
TI  - A characterization of solution gas flaring in Alberta.
AB  - Information reported here is the result of a detailed analysis of data on flared
      and vented solution gas in the Province of Alberta in 1999. A goal of
      characterizing these flares was to aid in the improved management of solution gas
      flaring. In total, 4499 oil and bitumen batteries reported flaring or venting
      with a combined gas volume of 1.42 billion m3. There was significant site-to-site
      variation in volumes of gas flared or vented, gas composition, and flare design.
      Approximately 5% of physical batteries generate 35.7% of the gas flared and
      vented from oil and bitumen batteries. Therefore, if one were to attempt to
      mitigate flaring, significant progress could be made by starting with only the
      largest sites. The monthly variability of gas volumes was considered because high
      variability could affect implementation of alternative technologies. It was found
      that slightly more than 40% of the sites were reasonably steady and had monthly
      deviations of 100% or less from the average flared volume. The variability in
      monthly volumes was less for the larger batteries. Data from individual well
      sites show significant variability in the relative concentrations of each of the
      major species contained in solution gas.

PMID- 11518291
TI  - EDTA-enhanced extraction of heavy metals from a coarse grained simulated soil by
      the CEHIXM process.
AB  - The effect of ethylenediaminetetraacetic acid (EDTA) in extracting heavy metal
      contaminants, namely Pb, Cd, Zn, and Mn, from soils with organometallic
      complexes, was explored using the coupled electric-hydraulic gradient assisted by
      ion exchange medium (CEHIXM) decontamination process. The experiments were
      conducted with a constant electric voltage of 50 DC V and a constant hydraulic
      flow rate of 4 cm3/min. The results obtained from the experiments demonstrated
      that EDTA was effective in extracting Pb, Cd, Zn, and Mn from soils in which
      acidic pH did not produce significant dissolution. Metal removal as high as 99%
      was achieved with 0.05 M EDTA solution within 200 hr.

PMID- 11518292
TI  - Waste incineration and pulmonary function: an epidemiologic study of six
      communities.
AB  - This study investigated the chronic effects of emissions from three different
      waste incinerators on pulmonary function of both healthy and sensitive subjects
      with chronic respiratory symptoms. Participants were 8-80 years old, not
      currently smoking, and living in one of three communities each with an
      incinerator or one of three matched comparison communities. In total, 1018
      subjects underwent a spirometric test once a year during 1992-1994. Exposure was
      assessed by three methods: living in an incinerator community; distance from the
      incinerator; and an incinerator exposure index, a function of the distance and
      direction of each subject's residence to the incinerator, days downwind, and
      average time spent outdoors. The results generally showed no statistically
      significant association between pulmonary function and these three incinerators,
      adjustment for gas oven/range use at home, length of residency, and smoking
      history in the mixed linear models. Two significant associations were that
      exposure to the hazardous waste incinerator in 1994 and to the municipal waste
      incinerator in 1993 were related to poor forced vital capacity. Sensitive
      subjects were not more adversely affected by incineration emissions than were hay
      fever or normal subjects. Possible explanations for the negative findings are low
      exposure levels and bias due to nondifferential misclassification of exposures.

PMID- 11518293
TI  - Measuring concentrations of volatile organic compounds in vinyl flooring.
AB  - The initial solid-phase concentration of volatile organic compounds (VOCs) is a
      key parameter influencing the emission characteristics of many indoor materials.
      Solid-phase measurements are typically made using solvent extraction or thermal
      headspace analysis. The high temperatures and chemical solvents associated with
      these methods can modify the physical structure of polymeric materials and,
      consequently, affect mass transfer characteristics. To measure solid-phase
      concentrations under conditions resembling those in which the material would be
      installed in an indoor environment, a new technique was developed for measuring
      VOC concentrations in vinyl flooring (VF) and similar materials. A 0.09-m2
      section of new VF was punched randomly to produce -200 0.78-cm2 disks. The disks
      were milled to a powder at -140 degrees C to simultaneously homogenize the
      material and reduce the diffusion path length without loss of VOCs. VOCs were
      extracted from the VF particles at room temperature by fluidized-bed desorption
      (FBD) and by direct thermal desorption (DTD) at elevated temperatures. The VOCs
      in the extraction gas from FBD and DTD were collected on sorbent tubes and
      analyzed by gas chromatography/mass spectrometry (GC/MS). Seven VOCs emitted by
      VF were quantified. Concentration measurements by FBD ranged from 5.1 microg/g VF
      for n-hexadecane to 130 microg/g VF for phenol. Concentrations measured by DTD
      were higher than concentrations measured by FBD. Differences between FBD and DTD
      results may be explained using free-volume and dual-mobility sorption theory, but
      further research is necessary to more completely characterize the complex nature
      of a diffusant in a polymer matrix.

PMID- 11518294
TI  - Artificial neural network-derived trends in daily maximum surface ozone
      concentrations.
AB  - Interannual variability in meteorological conditions can confound attempts to
      identify changes in ozone concentrations driven by reduced precursor emissions.
      In this paper, a technique is described that attempts to maximize the removal of
      meteorological variability from a daily maximum ozone time series, thereby
      revealing longer term changes in ozone concentrations with increased confidence.
      The technique employs artificial neural network [multilayer perceptron (MLP)]
      models, and is shown to remove more of the meteorological variability from U.S.
      ozone data than does a Kolmogorov-Zurbenko (KZ) filter and conventional
      regression-based technique.

PMID- 11518295
TI  - Effects of land use data on dry deposition in a regional photochemical model for
      eastern Texas.
AB  - Land use data are among the inputs used to determine dry deposition velocities
      for photochemical grid models such as the Comprehensive Air Quality Model with
      extensions (CAMx) that is currently used for attainment demonstrations and air
      quality planning by the state of Texas. The sensitivity of dry deposition and O3
      mixing ratios to land use classification was investigated by comparing
      predictions based on default U.S. Geological Survey (USGS) land use data to
      predictions based on recently compiled land use data that were collected to
      improve biogenic emissions estimates. Dry deposition of O3 decreased throughout
      much of eastern Texas, especially in urban areas, with the new land use data.
      Predicted 1-hr averaged O3 mixing ratios with the new land use data were as much
      as 11 ppbv greater and 6 ppbv less than predictions based on USGS land use data
      during the late afternoon. In addition, the area with peak O3 mixing ratios in
      excess of 100 ppbv increased significantly in urban areas when deposition
      velocities were calculated based on the new land use data. Finally, more detailed
      data on land use within urban areas resulted in peak changes in O3 mixing ratios
      of approximately 2 ppbv. These results indicate the importance of establishing
      accurate, internally consistent land use data for photochemical modeling in urban
      areas in Texas. They also indicate the need for field validation of deposition
      rates in areas experiencing changing land use patterns, such as during urban
      reforestation programs or residential and commercial development.

PMID- 11518296
TI  - Investigation of the potential antimicrobial efficacy of sealants used in HVAC
      systems.
AB  - Recent experiments confirm field experience that duct cleaning alone may not
      provide adequate protection from regrowth of fungal contamination on fiberglass
      duct liner (FGDL). Current recommendations for remediation of fungally
      contaminated fiberglass duct materials specify complete removal of the materials.
      But removal of contaminated materials can be extremely expensive. Therefore, a
      common practice in the duct-cleaning industry is the postcleaning use of
      antimicrobial surface coatings with the implication that they may contain or
      limit regrowth. Little information is available on the efficacy of these
      treatments. This paper describes a study to evaluate whether three commercially
      available antimicrobial coatings, placed on a cleaned surface that 1 year
      previously had been actively growing microorganisms, would be able to prevent
      regrowth. The three coatings contained different active antimicrobial compounds.
      All three of the coatings were designed for use on heating, ventilation, and air
      conditioning (HVAC) system components or interior surfaces of lined and unlined
      duct systems. Coating I was a polyacrylate copolymer containing zinc oxide and
      borates. Coating II was an acrylic coating containing decabromodiphenyl oxide and
      antimony trioxide. Coating III was an acrylic primer containing a phosphated
      quaternary amine complex. The study included field and laboratory assessments.
      The three treatments were evaluated in an uncontrolled field setting in an actual
      duct system. The laboratory study broadened the field study to include a range of
      humidities under controlled conditions. Both static and dynamic chamber
      laboratory experiments were performed. The results showed that two of the three
      antimicrobial coatings limited the regrowth of fungal contamination, at least in
      the short term (the 3-month time span of the study); the third did not. Before
      use in the field, testing of the efficacy of antimicrobial coatings under
      realistic use conditions is recommended because antimicrobials have different
      baseline activities and interact differently with the substrate that contains
      them and their local environment.

PMID- 11518297
TI  - Ozone predictions in Atlanta, Georgia: analysis of the 1999 ozone season.
AB  - Ozone prediction has become an important activity in many U.S. ozone
      nonattainment areas. In this study, we describe the ozone prediction program in
      the Atlanta metropolitan area and analyze the performance of this program during
      the 1999 ozone-forecasting season. From May to September, a team of 10 air
      quality regulators, meteorologists, and atmospheric scientists made a daily
      prediction of the next-day maximum 8-hr average ozone concentration. The daily
      forecast was made aided by two linear regression models, a 3-dimensional air
      quality model, and the no-skill ozone persistence model. The team's performance
      is compared with the numerical models using several numerical indicators. Our
      analysis indicated that (1) the team correctly predicted next-day peak ozone
      concentrations 84% of the time, (2) the two linear regression models had a better
      performance than a 3-dimensional air quality model, (3) persistence was a strong
      predictor of ozone concentrations with a performance of 78%, and (4) about half
      of the team's wrong predictions could be prevented with improved meteorological
      predictions.

PMID- 11518298
TI  - Sorption and biodegradation of vapor-phase organic compounds with wastewater
      sludge and food waste compost.
AB  - To test the possible use of composted food waste and wastewater sludge as
      biofilters to treat gas-phase volatile organic compounds (VOCs), batch
      experiments were conducted with an isolated strain that could degrade aromatic
      compounds under aerobic conditions. A benzene and trichloroethylene (TCE) mixture
      was used as the gas-phase pollutant in experiments with composted food waste,
      sludge, and soil. Under aerobic conditions, benzene was degraded as a primary
      substrate and TCE was degraded cometabolically, with water contents varying from
      6 to 60% (volume of water added/volume of solid). Optimal water content for VOC
      removal was 12% for the soil, 36% for the composted food waste, and 48% for the
      sludge. The extent of VOC sorption and biodegradation at the optimal water
      content was different for each material. With the same initial VOC concentration,
      more VOCs were removed by sorption onto the composted food waste and the sludge,
      while less VOCs were biodegraded in comparison with the results using soil. The
      reason the biodegradation in the soil was greater may be partly attributed to the
      fact that, due to less sorption, the aqueous-phase concentration of VOCs, which
      microorganisms could utilize as a carbon source or cometabolize, was higher. We
      also speculate that the distribution of microorganisms in each medium affects the
      rate of biodegradation. A large number of microorganisms were attached to the
      composted food waste and sludge. Mass transfer of VOCs and oxygen to these
      microorganisms, which appear to have been heterogeneously distributed in
      clusters, may have been limited, resulting in hindered biodegradation.

PMID- 11518299
TI  - Tryptophan catabolism in Brevibacterium linens as a potential cheese flavor
      adjunct.
AB  - Attempts to develop a desirable reduced fat Cheddar cheese are impeded by a
      propensity for flavor defects such as meaty-brothy, putrid, fecal, and unclean
      off-flavors in these products. Recent studies suggest aromatic amino acid
      catabolism of starter, adjunct, and nonstarter lactic acid bacteria significantly
      impact off-flavor development. The objective of this study was to delineate
      pathways for catabolism of tryptophan (Trp) in Brevibacterium linens, a cheese
      flavor adjunct, and to determine the potential for this organism to contribute to
      this defect. Growth and production of aromatic compounds from Trp by B. linens
      BL2 were compared in two incubated conditions (laboratory and a cheese-like
      environment). A chemically defined medium was used to determine the cellular
      enzymes and metabolites involved in Trp catabolism. Trp was converted to
      kynurenine, anthranilic acid, and three unknown compounds in laboratory
      conditions. The accumulation of other unknown compounds in the culture
      supernatant in laboratory conditions indicated that B. linens BL2 degraded Trp by
      various routes. Up to 65% of Trp was converted to anthranilic acid via the
      anthranilic acid pathway. To assess this potential before cheese making, the
      cells were incubated in cheese-like conditions (15 degrees C, pH 5.2, no sugar
      source, 4% NaCl). Trp was not utilized by BL2 incubated in this condition. Enzyme
      studies using cell-free extracts of cells incubated in laboratory conditions and
      assayed at optimal and nonoptimal enzyme assay conditions revealed Trp
      transaminase (EC 2.6.1.27) was active before enzymes of the anthranilic acid
      pathway were detected. The products of Trp transaminase activity were not,
      however, found in the culture supernatant, indicating these intermediates were
      not exported nor accumulated by the cells. Enzymes assayed in nonoptimal
      conditions had considerably lower enzyme activities than found in laboratory
      incubation conditions. Based on these results, we hypothesize that these enzymes
      are not likely to be involved in the formation of compounds associated with off
      flavors in Cheddar cheese.

PMID- 11518300
TI  - Expression of clpX, an ATPase subunit of the Clp protease, is heat and cold shock
      inducible in Lactococcus lactis.
AB  - In this study, the clpX gene and surrounding sequences were cloned and sequenced
      from Lactococcus lactis. The putative clpX gene encodes a 411 amino acid
      polypeptide with a predicted molecular weight of 45.8 kDa. Analysis of the
      relative levels of clpX transcript revealed that in addition to a role in
      proteolysis of heat damaged proteins, ClpX may also be involved in
      cryoprotection.

PMID- 11518301
TI  - Plasminogen activation system in goat milk and its relation with composition and
      coagulation properties.
AB  - The activity of plasmin (PL), plasminogen (PG), and plasminogen activator (PA)
      and their correlation with goat milk components and milk clotting parameters were
      investigated. Seven late-lactating Saanen goats were used to provide milk samples
      that were analyzed for PL, PG, and PA activity (colorimetric assay) fat, protein,
      noncasein nitrogen, nonprotein nitrogen, casein content, and somatic cell count
      (SCC). Milk clotting parameters (rennet coagulating time = coagulation time; K20
      = firming rate of curd; A30 = curd firmness) were measured with a formagraph.
      Average milk yield and composition were similar to those previously observed in
      other studies. Plasmin, PG, and PA activity, expressed as units/ml, were,
      respectively, 20.04 +/- 0.94, 3.21 +/- 0.04, and 1154 +/- 57.61. Plasminogen
      activity was surprisingly low compared with other species (bovine, ovine), but it
      was consistent with the high activity of PA. A negative significant correlation
      was observed between PL and milk casein content. The correlation coefficients
      between PL and casein/protein ratio and PA and casein/protein ratio were negative
      and significant. A positive significant correlation was observed between PL and
      rennet clotting time and PA and rennet clotting time. Also positive was the
      correlation between PL and K20 and PA and K20. The plasmin activity was
      negatively correlated with A30. High plasmin and plasminogen activator activity
      in goat milk appeared to be negatively related with coagulating properties in
      late lactation, most probably via degradation of casein due to plasmin activity.

PMID- 11518302
TI  - Immunization with Staphylococcus aureus lysate incorporated into microspheres.
AB  - Antibiotics are of limited value against Staphylococcus aureus due to development
      of resistant strains, scar tissue formation, and blockage of ducts due to
      inflammation. Though macrophages are the predominant cell type in the mammary
      gland, they are primarily scavenger cells and are not effective against bacteria
      entering the gland. Neutrophil phagocytosis is the bovine's primary defense
      against S. aureus mastitis. Attempts to develop vaccines that enhance neutrophil
      phagocytosis by stimulating production of opsonizing antibodies to S. aureus have
      met with limited success because of the low immunogenicity of the
      exopolysaccharide capsule surrounding S. aureus. Staphylococcus aureus can also
      adhere to and penetrate epithelial tissue. This study was conducted to determine
      whether lysates of S. aureus encapsulated in biodegradable microspheres would
      increase the production of opsonizing antibodies to capsule and block adherence.
      Four groups of four cows each were injected with 1 ml of the respective treatment
      in the area of the supramammary lymph node and 1 ml in the hip muscle. The
      treatments were: lysate in NaCl, lysate in Freund's incomplete adjuvant (FICA),
      lysate in microspheres in NaCl, and lysate in microspheres in FICA. Antigen in
      microspheres produced a similar antibody response to antigen emulsified in FICA,
      but to a lesser magnitude. Antigen in microspheres produced antibodies that were
      more opsonic for neutrophils at 20 and 52 wk postimmunization and inhibited S.
      aureus adherence to mammary epithelium. Ability to control antigen release and
      presentation, and the benefit of a single injection for long-term immunity using
      microspheres warrants additional studies.

PMID- 11518303
TI  - Effect of urea during in vitro maturation on nuclear maturation and embryo
      development of bovine cumulus-oocyte-complexes.
AB  - High concentrations of urea in reproductive tract fluids are detrimental to
      bovine reproduction. Therefore, in experiment 1, the effect of 6 mM urea on
      nuclear maturation of cumulus-oocyte-complexes (COC) collected from abattoir
      ovaries was studied. After 4, 8, 12, 16, 20, and 24 h of in vitro maturation, the
      nuclear stages of samples of the COC were determined. During the first 8 h of
      maturation, germinal vesicle breakdown and chromosome condensation, resulting in
      the metaphase I stage, occurred at higher rates in the presence of urea.
      Segregation of the chromatids and extrusion of the polar body seemed to be
      impaired in the presence of urea, resulting in a higher percentage of oocytes
      arrested in metaphase I or telophase, and a lower percentage of oocytes in
      metaphase II after 24 h of maturation. Overall, nuclear progression of COC
      matured in the presence of urea differed from COC matured in control medium. In
      experiment 2, COC were matured for 24 h either in the presence or absence of 6 mM
      urea followed by in vitro fertilization and culture. After fertilization, a
      sample of the COC was fixed and stained to determine the fertilization rate. The
      cleavage rate was determined 3 d after start of maturation, and the stage of
      embryonic development was recorded 7 and 9 d after start of maturation. Based on
      cultured oocytes, urea in the maturation medium decreased the subsequent
      percentage of fertilization, cleavage, and development on d 7 and 9 (43.2, 56.1,
      14.8, and 18.2%, respectively for urea vs. 64.1, 68.8, 22.4, and 23.9%,
      respectively for the control group). Embryonic development as a percentage of
      cleaved oocytes was not significantly affected by urea. Therefore, negative
      effects of urea were evident primarily during oocyte maturation and
      fertilization.

PMID- 11518304
TI  - Forecasting herd structure and milk production for production risk management.
AB  - Substantial increases in milk price volatility have resulted from changes in
      federal dairy policies. For a dairy farm, however, monthly gross milk receipts
      are a function of unit price and quantity produced. Both can vary substantially
      over time. Therefore, to be effective, risk management strategies must address
      milk and input price volatility (price risk management) and fluctuations in milk
      production per cow and cow numbers (production risk management). Herd milk
      production through time can be modeled as a discrete stochastic process using
      finite Markov chains. Cows at time t = 0 are assigned to homogeneous production
      cells in four-dimensional arrays with coordinates determined by parity (1, 2, 3),
      week in milk (1, ..., 104), pregnancy status (0, 1), and week pregnant (1, ...,
      40). The processes of aging, pregnancy, involuntary cull, voluntary cull,
      abortion, dry-off, and freshening from week i-1 to week i are accounted for,
      using nonstationary transition probabilities. Bayesian estimates of transition
      probabilities are derived from historical herd data, assuming that individual
      outcomes are from Bernoulli distributions. The values of parameters theta(i) for
      the Bernoulli distributions are unknown but have prior distributions that follow
      beta distributions with parameters alpha(i) and beta(i) estimated from historical
      data. Herd observations are then used to generate posterior distributions of
      theta(i), also from beta distributions. Projecting from one week to the next is
      accomplished by moving virtual animals from one production cell to the next based
      on the transition probability assigned to that path. Summing production estimates
      and variances of all independent cells provides for an expected herd production
      with an associated variance. As expected, the forecast variance increases with
      time, reflecting increased uncertainty of distant projections. Model validation
      presents an interesting problem because future observations used for validation
      are under human control and are not independent of the forecast.

PMID- 11518305
TI  - Effect of adding alum or zeolite to dairy slurry on ammonia volatilization and
      chemical composition.
AB  - Development of cost-effective amendments for treating dairy slurry has become a
      critical problem as the number of cows on farms continues to grow and the acreage
      available for manure spreading continues to shrink. To determine effectiveness
      and optimal rates of addition of either alum or zeolite to dairy slurry, we
      measured ammonia emissions and resulting chemical changes in the slurry in
      response to the addition of amendments at 0.4, 1.0, 2.5, and 6.25% by weight.
      Ammonia volatilization over 96 h was measured with six small wind tunnels with
      gas scrubbing bottles at the inlets and outlets. Manure samples from the start
      and end of trials were analyzed for total nitrogen and phosphorus, and were
      extracted with 0.01 M CaCl2, 1.0 M KCl, and water with the extracts analyzed for
      ammonium nitrogen, phosphorous, aluminum, and pH. The addition of 6.25% zeolite
      or 2.5% alum to dairy slurry reduced ammonia emissions by nearly 50 and 60%,
      respectively. Alum treatment retained ammonia by reducing the slurry pH to 5 or
      less. In contrast, zeolite, being a cation exchange medium, adsorbed ammonium and
      reduced dissolved ammonia gas. In addition, alum essentially eliminated soluble
      phosphorous. Zeolite also reduced soluble phosphorous by over half, but the
      mechanism for this reduction is unclear. Alum must be carefully added to slurry
      to avoid effervescence and excess additions, which can increase soluble aluminum
      in the slurry. The use of alum or zeolites as on-farm amendment to dairy slurry
      offers the potential for reducing ammonia emissions and soluble phosphorus in
      dairy slurry.

PMID- 11518306
TI  - Tail-docking alters fly numbers, fly-avoidance behaviors, and cleanliness, but
      not physiological measures.
AB  - Tail docking is an animal well-being issue not only regarding the docking
      procedures but also because of concerns during fly season. To address the latter
      question, we selected eight cows that had been tail-docked in a previous
      experiment and eight nondocked cows matched by stage of lactation. Physiological,
      immunological, and behavioral measures were used to evaluate the well being of
      those cows housed in a tie-stall barn during fly season for 5 consecutive days.
      Behavior was observed for 5-min interval instantaneous scan samples for 1 h each
      at 0800, 1200, and 1600 h. Flies were counted before behavior observations. Blood
      samples were taken daily for plasma and leukocyte separation. Cows were scored on
      d 5 for cleanliness on a five-point scale. Docked cows were cleaner, but fly
      counts of docked cows were greater for total fly counts and rear leg counts.
      However, counts were not different on front legs. Time of day was significant, so
      each time of day was analyzed separately. Docked cows were observed to exhibit
      fewer tail swings at 0800 h, but docked cows tended to ruminate more at that
      time. Docked cows tended to stand less at the 1200 h observation. Total fly
      avoidance behaviors were greater for all cows at the 1600-h observation. Only
      tail swings tended to be more frequent with docked cows, but foot stomps occurred
      only in the docked cows. Lymphocyte phenotypes, acute-phase proteins, and
      immunoglobulin concentrations did not differ. In conclusion, although docked cows
      were cleaner, as the fly numbers increase throughout the day, fly-avoidance
      behaviors also increased and foot stomping appeared as an alternative method for
      fly avoidance by docked cows.

PMID- 11518307
TI  - Analysis time and lactation stage influence on lactoperoxidase system components
      in dairy ewe milk.
AB  - To study the effect of time elapsed from the moment of taking samples on
      lactoperoxidase system components, we analyzed the activity of the
      lactoperoxidase enzyme and the concentrations of thiocyanate and hydrogen
      peroxide in 46 individual samples of Manchega ewe milk. Samples were maintained
      at a temperature of 4 degrees C until analysis, which took place at 6, 12, 24,
      and 48 h after extraction. Decreases were observed in lactoperoxidase activity
      when the analyses were performed at 48 h and in the thiocyanate and hydrogen
      peroxide concentrations at 12 h compared with those carried out earlier.
      Consequently, when the components of the lactoperoxidase system or its
      antibacterial activity are studied, the time elapsed since the sampling commenced
      must be taken into account. Similarly, the time elapsed is important when
      carrying out bacterial counts or residue screening by microbiological methods,
      during which the lactoperoxidase system may interfere. To study the component
      changes in the lactoperoxidase system during lactation, samples obtained 15, 30,
      45, 60, 75, 90, 105, 120, and 135 d postpartum from 48 Manchega ewes were used.
      Average lactoperoxidase activity, thiocyanate, and hydrogen peroxide
      concentrations were 3.46 U/ml, 6.89 mg/L, and 0.39 mg/L, respectively, with
      significant variations throughout lactation. The thiocyanate and hydrogen
      peroxide levels at different lactation stages seemed to be insufficient to
      activate the lactoperoxidase system. Nevertheless, this could be achieved by
      adding 5 mg/L of thiocyanate and 8 mg/L of hydrogen peroxide at any time during
      lactation.

PMID- 11518308
TI  - What affects the costs of raising replacement dairy heifers: a multiple-component
      analysis.
AB  - A DP model of a dairy replacement herd was developed to analyze the impact of
      different dairy and replacement herd variables on the cost of rearing
      replacements for a representative dairy herd of 100 cows. A model was developed
      with Pennsylvania and US average information as the basis for the parameters. We
      used age at first calving of 25 mo, calving interval of 13 mo, herd-culling rate
      of 25%, and preweaned calf death of 10% as the base for comparison. We examined
      the impact of factors including age at first calving, calving interval, PDR, and
      the number of replacements required. From the base model, the total cost of
      rearing sufficient replacements for a 100-cow herd was $32,344. A reduction in
      culling rate to 20%, holding all other factors fixed, caused the net costs of
      raising replacements for the dairy herd to fall by $7968 or 24.6%. Increasing the
      culling rate above 25% led to a deficit in replacements for maintaining constant
      herd size, assuming a closed herd. The average age at first calving also affected
      the net costs of raising replacement heifers; reducing the age at first calving
      by 1 mo lowered the cost of a replacement program by $1400 or 4.3%. Changes in
      the length of the calving interval or in the PDR had marginal impacts on the net
      costs of replacement programs when compared with either herd-culling rate or
      average age at first calving.

PMID- 11518309
TI  - Conjugated linoleic acid and other beneficial fatty acids in milk fat from cows
      fed soybean meal, fish meal, or both.
AB  - Twelve multiparous Holstein cows at 48 +/- 8 DIM were used in a 4 x 4 Latin
      square with 21-d periods to determine the effect of replacing soybean meal with
      fish meal on feed intake, milk yield, and milk composition. Fish meal substituted
      for soybean meal on an isonitrogenous basis at 0, 25, 50, and 100% of
      supplemental protein. Total mixed diets were (DM basis) 25% corn silage, 25%
      alfalfa hay, and 50% concentrate mix. Intake of DM (27.9, 27.8, 26.1, and 25.8
      kg/d for diets 1 to 4, respectively) was similar for all diets. Milk yield (37.5,
      37.8, 37.2, and 37.7 kg/d) was not affected by diets. Milk protein percentages
      (3.23, 3.24, 3.31, and 3.35) increased with 100% fish meal supplementation and
      tended to be higher with 50% fish meal supplementation compared with 100% soybean
      meal diet. Milk fat percentages (3.18, 2.99, 3.04, and 2.87) and yield were lower
      with the 100% fish meal than with the 100% soybean meal diet. Concentration of n
      3 fatty acids in milk fat (0.54, 0.56, 0.63, and 0.72 g/100 g fatty acids)
      increased as the proportion of fish meal in the diet increased. Concentrations of
      c9,t11 conjugated linoleic acid (CLA; 0.39, 0.44, 0.46, and 0.72 g/100 g fatty
      acids) and transvaccenic acid (TVA; 1.09, 1.19, 1.28, and 1.54 g/100 g of fatty
      acids) were higher with the 100% fish meal diet than with the 100% soybean meal
      diet. A total replacement of soybean meal with fish meal in the diet of lactating
      cows increased milk protein percentages and the beneficial fatty acids (CLA, TVA,
      and n-3 FA) in milk fat.

PMID- 11518310
TI  - Gastric proteinase digestion of caseins in newborn pups of the mouse.
AB  - Casein micelles of mouse milk consist of alpha-, beta-, gamma-, and kappa
      caseins. By digestion with alkaline phosphatase, they were separated as an
      independent band by sodium dodecyl sulfate (SDS)-polyacrylamide gel
      electrophoresis (PAGE). The compositions of alpha-, beta-, gamma-, and kappa
      caseins were 24.3, 25.1, 9.4, and 41.2% in colostrum, and 36.8, 15.6, 11.9, and
      35.7% in mature milk, respectively. Zero-day-old pups were allowed to access
      either colostrum or mature milk, and the aggregated milk in the stomach was
      analyzed by SDS-PAGE. Caseins in colostrum were digested more rapidly and
      efficiently than those in mature milk. Among the seven peptides present in the
      aggregated caseins, four peptides were colostrum-specific and derived from alpha-
      and gamma-caseins. It was expected that colostrum-specific and soluble peptides
      were generated from alpha- and gamma-caseins through gastric proteinase
      digestion. Amino acid sequence analysis and the pH of the aggregated milk
      suggested that caseins in the stomach were digested by a chymotrypsin-like
      proteinase. Caseins in colostrum were different from those in mature milk, with
      respects to the casein composition as well as the gastric proteinase sensitivity.
      It is concluded that the lactating mice on the day of parturition supply
      particular caseins to their young.

PMID- 11518311
TI  - Livestock drinking water microbiology and the factors influencing the quality of
      drinking water offered to cattle.
AB  - The microbial quality of livestock drinking water was evaluated in 473 cattle
      water troughs located at 99 different cattle operations. The mean log10
      transformed coliform and Escherichia coli concentrations per milliliter of trough
      water were 1.76 +/- 1.25 (SD) and 0.98 +/- 1.06 (SD), respectively. The degree of
      E. coli contamination was positively associated with the proximity of the water
      trough to the feedbunk, protection of the trough from direct sunlight, lower
      concentrations of protozoa in the water, and warmer weather. Salmonella sp. were
      isolated from 2/235 (0.8%) troughs and shigatoxigenic-E. coli O157 was recovered
      from 6/473 (1.3%) troughs. Four experimental microcosms simulating cattle water
      troughs were used to further evaluate the effects of protozoal populations on the
      survival of E. coli O157 in cattle water troughs. Escherichia coli O157 of bovine
      fecal origin proliferated in all microcosms. Reduction of protozoal populations
      by treatment with cycloheximide was associated with increased persistence of E.
      coli O157 concentrations in the microcosms. Water troughs are a major source of
      exposure of cattle to enteric bacteria, including a number of foodborne
      pathogens, and this degree of bacterial contamination appeared to be associated
      with potentially controllable factors.

PMID- 11518312
TI  - Feeding value of corn silage estimated with sheep and dairy cows is not altered
      by genetic incorporation of Bt1376 resistance to Ostrinia nubilalis.
AB  - A genetically modified Bt176 corn hybrid (Rh208Bt)--providing control of European
      corn borer damage--and the conventional isogenic hybrid (Rh208)--harvested as
      whole plant silage--were evaluated in three separate feeding trials to verify
      that the in vivo feeding value was substantially equivalent among modified and
      conventional hybrids. In the first trial, after a week of preexperiment, two sets
      of six Texel sheep, housed in digestibility crates, were fed silage sources of
      Rh208 and Rh208Bt hybrids, and silage of three additional control varieties of
      low, intermediate, and high feeding value (Rh289, Adonis, and Adonis bm3) for 1
      wk. Feed offered to sheep was adjusted to maintenance requirements based on
      metabolic body weight. Agronomic and biochemical traits were similar among the
      Rh208 and Rh208Bt hybrids. Organic matter digestibility (67.1 and 67.6%), crude
      fiber digestibility (52.9 and 54.2%), and neutral detergent fiber digestibility
      (50.2 and 49.0%) were not significantly different among Rh208 and Rh208Bt
      hybrids. In the second trial, two sets of 24 Holstein cows were fed silage from
      Rh208 and Rh208Bt corn hybrids for 13 wk, 9 wk after calving, and including 2 wk
      of preexperiment. Fat-corrected milk yield (31.3 and 31.4 kg/d), protein content
      (31.7 and 31.6 g/kg) and fat content (36.7 and 37.0 g/kg) in milk of dairy cows
      were unaffected by hybrid source. Body weight gains of cattle were not different.
      However, intake was significantly higher in cows fed Rh208Bt silage. In the third
      trial, five midlactation multiparous Holstein cows were successively fed the
      silage from Rh208 and Rh208Bt corn hybrids 2 or 3 wk. Data were considered only
      for the last week of each period. There were no significant effects on protein
      fractions, fatty acid composition, or coagulation properties of milk between
      Rh208 and Rh208Bt fed cattle. Cattle and sheep can perform equally well with a
      conventional or a genetically modified Bt176 corn silage.

PMID- 11518313
TI  - Construction of optimum index to maximize overall response across countries in
      the presence of genotype x environment interaction.
AB  - Sire effect is partitioned into two parts: constant effect unaffected by
      environments and interaction effect specific to each environment and responsible
      for genotype x environment (GE) interaction. Response to selection for constant
      effect is the same across environments, thus increasing genetic stability,
      whereas response to selection for interaction effect would vary depending upon
      environments. The conventional measure of GE interaction based on genetic
      correlation (gammaG) considers both constant and interaction components even
      though the constant component plays no role in GE interaction. In contrast, the
      proposed measure of GE interaction based on interaction correlation (gammaI)
      deals only with interaction component responsible for GE interaction and thus
      indicates the intensity of GE interaction generated by responsible genes.
      Constant and interaction effects with different economic weights were combined
      into optimum index to improve both genetic stability and overall response across
      countries (countries represent environments). Optimum index was more efficient
      than the unpartitioned index which was more efficient than selection in a single
      country except when economic weights between constant and interaction effects
      were equal. Optimum index and unpartitioned index were the same when these
      economic weights were equal. The advantage of optimum index over the other
      selection methods increases as the intensity of GE interaction increases. When
      the relative economic weights are equivalent among countries and between constant
      and interaction effects, selection in a country with a larger sire variance is
      more effective than selection in a country with a smaller sire variance.

PMID- 11518314
TI  - Assessment of a commercially available early conception factor (ECF) test for
      determining pregnancy status of dairy cattle.
AB  - The Early Conception Factor (ECF) test is a commercially available qualitative
      assay that reportedly detects a pregnancy-associated glycoprotein present in
      bovine serum within 48 h after conception. One concern with previous assessments
      of this test is that animals with viable embryos early during pregnancy that
      subsequently undergo embryonic loss before pregnancy diagnosis increase the rate
      of false-positive results and bias the assessment. To preclude this possibility,
      noninseminated Holstein cows (n = 9) and heifers (n = 8) were evaluated as an
      unequivocal source of nonpregnant animals, and Holstein cows (n = 17) and heifers
      (n = 1) inseminated at estrus and in which at least one embryo of transferable
      quality was recovered at a nonsurgical flush 6 d after artificial insemination
      were evaluated as an unequivocal source of pregnant animals. Blood samples were
      collected from all animals 6 d after estrus, which was immediately before embryo
      collection in pregnant animals. Each serum sample was evaluated using two ECF
      test cassettes (tests 1 and 2), and the result of each test cassette was
      interpreted by two independent readers (readers 1 and 2). Test sensitivity,
      specificity, positive predictive value, negative predictive value, and accuracy
      were 86, 4, 49, 23, and 46%, respectively. Although the observed agreement
      between readers (91% for test 1; 89% for test 2) and between tests for the same
      serum sample (94% for reader 1; 91% for reader 2) was high, the overall rates of
      false-positive and false-negative ECF test results were 96 and 14%, respectively.
      We conclude that the ECF test is an unreliable method for determining pregnancy
      status of dairy cattle on day 6 after estrus.

PMID- 11518315
TI  - Producer satisfaction, efficiency, and investment cost factors of different
      milking systems.
AB  - A modernization survey was used to determine producer satisfaction, efficiency,
      and investment cost measures of different milking systems. The 301 producers
      included in this study expanded herd size by at least 50% for smaller herds (60
      to 100 cows), or 40% for larger herds, (>100 cows) between 1994 and 1998. The
      milking systems analyzed and compared were stall barn with pipeline, flat barn
      parlor walk through and back-out, and herringbone or parallel parlor in old barn
      or new building. Investment costs per cow were higher for pit parlor in new
      building, $979. Parallel parlors had a higher cost per milking unit, $13,201, and
      cost per cow, $860, than herringbone, $8944 and $582, respectively. Herringbone
      parlors were used more hours per day, 10.75, than parallel parlors, 8.84, of
      similar size. Pit parlors in new buildings were more labor efficient, as measured
      by cows per worker hour, than stall barns with pipeline or flat parlor or pit
      parlors in old barns. Herringbone and parallel parlor in new building were
      similar for cows per hour (82 and 83) and cows per worker hour (41 and 43).
      Parallel or herringbone parlors in old barns had fewer cows per hour (63 and 58)
      than parallel or herringbone parlors in new buildings. Survey respondents showed
      greater satisfaction for time spent milking, physical comfort of milker, and milk
      quality for parlor types over stall barn with pipeline. Safety of operator
      satisfaction was higher for pit parlors than flat parlors or stall barn. No
      difference in satisfaction was observed between parallel and herringbone parlors.

PMID- 11518316
TI  - Overview of progeny-test programs of artificial-insemination organizations in the
      United States.
AB  - Characteristics of progeny-test (PT) programs of artificial insemination (AI)
      organizations in the United States were examined for changes since 1960. Mean
      number of bulls that were progeny tested annually by major AI organizations
      during the mid 1990s was 11 for Ayrshires, 24 for Brown Swiss, 21 for Guernseys,
      1261 for Holsteins, 112 for Jerseys, and 3 for Milking Shorthorns. Mean parent
      age at progeny-test (PT) bull birth decreased except for Milking Shorthorns; mean
      age of maternal grandsire at bull birth decreased for Holsteins and Jerseys but
      increased for other breeds. For Holsteins, mean ancestor ages at PT bull birth
      were 85 mo for sires, 47 mo for dams, and 136 mo for maternal grandsires during
      the mid 1990s. Percentage of PT bulls that resulted from embryo transfer
      increased to 78% for Brown Swiss and 80% for Holsteins by 1999. Inbreeding in PT
      bulls increased over time and ranged from 3.8% for Brown Swiss to 6.4% for
      Jerseys (5.6% for Holsteins) during the mid 1990s. Mean numbers of daughters and
      herds per PT bull generally declined except for Holsteins, which increased during
      the early 1990s to 61 daughters and 44 herds. Mean number of states in which PT
      daughters are located increased; for Holstein PT bulls during 1994, 22% of
      daughters were in California, 13% in Wisconsin, 12% in New York, and 10% in
      Pennsylvania and Minnesota. Percentage of first-lactation cows that were PT
      daughters increased and ranged from 6% for Milking Shorthorns to 22% for
      Ayrshires (14% for Holsteins) during 1998. Percentage of PT daughters that were
      registered declined and was 19% for Holsteins and around 80% for other breeds.

PMID- 11518317
TI  - Sequence heterogeneity of the ten rRNA operons in Clostridium perfringens.
AB  - We have cloned and sequenced rRNA operons of Clostridium perfringens strain 13
      and analyzed the sequence structure in view of the phylogenesis. The organism had
      ten copies of rRNA operons all of that comprised of 16S, 23S and 5S rDNAs except
      for one operon. The operons clustered around the origin of replication, ranging
      within one-third of the whole genome sequence as it is arranged in a circle.
      Seven operons were transcribed in clockwise direction, and the remaining three
      were transcribed in counter clockwise direction assuming that the gyrA was
      transcribed in clockwise direction. Two of the counter clockwise operons
      contained tRNA(Ile) genes between the 16S and 23S rDNAs, and the other had a
      tRNA(Ile) genes between the 16S and 23S rDNAs and a tRNA(Asn) gene in the place
      of the 5S rDNA. Microheterogeneity was found within the rRNA structural genes and
      spacer regions. The length of each 16S, 23S and 5S rDNA were almost identical
      among the ten operons, however, the intergenic spacer region of 16S-23S and 23S
      5S were variable in the length depending on loci of the rRNA operons on the
      chromosome. Nucleotide sequences of the helix 19, helix 19a, helix 20 and helix
      21 of 23S rDNA were divergent and the diversity appeared to be correlated with
      the loci of the rRNA operons on the chromosome.

PMID- 11518318
TI  - Flagellin gene sequence variation in the genus Pseudomonas.
AB  - Flagellin gene (fliC) sequences from 18 strains of Pseudomonas sensu stricto
      representing 8 different species, and 9 representative fliC sequences from other
      members of the gamma sub-division of proteobacteria, were compared. Analysis was
      performed on N-terminal, C-terminal and whole fliC sequences. The fliC analyses
      confirmed the inferred relationship between P. mendocina, P. oleovorans and P.
      aeruginosa based on 16S rRNA sequence comparisons. In addition, the analyses
      indicated that P. putida PRS2000 was closely related to P. fluorescens SBW25 and
      P. fluorescens NCIMB 9046T, but suggested that P. putida PaW8 and P. putida
      PRS2000 were more closely related to other Pseudomonas spp. than they were to
      each other. There were a number of inconsistencies in inferred evolutionary
      relationships between strains, depending on the analysis performed. In
      particular, whole flagellin gene comparisons often differed from those obtained
      using N- and C-terminal sequences. However, there were also inconsistencies
      between the terminal region analyses, suggesting that phylogenetic relationships
      inferred on the basis of fliC sequence should be treated with caution. Although
      the central domain of fliC is highly variable between Pseudomonas strains, there
      was evidence of sequence similarities between the central domains of different
      Pseudomonas fliC sequences. This indicates the possibility of recombination in
      the central domain of fliC genes within Pseudomonas species, and between these
      genes and those from other bacteria.

PMID- 11518319
TI  - Taxonomic characterization of new alkaliphilic and alkalitolerant methanotrophs
      from soda lakes of the Southeastern Transbaikal region and description of
      Methylomicrobium buryatense sp.nov.
AB  - Five strains of obligate methanotrophic bacteria (4G, 5G, 6G, 7G and 5B) isolated
      from bottom sediments of Southeastern Transbaikal soda lakes (pH 9.5-10.5) are
      taxonomically described. These bacteria are aerobic, Gram-negative monotrichous
      rods having tightly packed cup-shaped structures on the outer cell wall surface
      (S-layers) and Type I intracytoplasmic membranes. All the isolates possess
      particulate methane monooxygenase (pMMO) and one strain (5G) also contains
      soluble methane monooxygenase (sMMO). They assimilate methane and methanol via
      the ribulose monophosphate pathway (RuMP). The isolates are alkalitolerant or
      facultatively alkaliphilic, able to grow at pH 10.5-11.0 and optimally at pH 8.5
      9.5. These organisms are obligately dependent on the presence of sodium ions in
      the growth medium and tolerate up to 0.9-1.4 M NaCl or 1 M NaHCO3. Although being
      mesophilic, all the isolates are resistant to heating (80 degrees C, 20 min),
      freezing and drying. Their cellular fatty acids profiles primarily consist of
      C(16:1). The major phospholipids are phosphatidylethanolamine and
      phosphatidylglycerol. The main quinone is Q-8. The DNA G+C content ranges from
      49.2-51.5 mol %. Comparative 16S rDNA sequencing showed that the newly isolated
      methanotrophs are related to membres of the Methylomicrobium genus. However, they
      differ from the known members of this genus by DNA-DNA relatedness. Based on
      pheno- and genotypic characteristics, we propose a new species of the genus
      Methylomicrobium Methylomicrobium buryatense sp. nov.

PMID- 11518320
TI  - New DNA-DNA hybridization and phenotypic data on the species Aeromonas
      ichthiosmia and Aeromonas allosaccharophila: A. ichthiosmia Schubert et al. 1990
      is a later synonym of A. veronii Hickman-Brenner et al. 1987.
AB  - Previously, a DNA fingerprinting study based on Amplified Fragment Length
      Polymorphism (AFLP) analysis has revealed a possible genotypic resemblance of the
      species Aeromonas ichthiosmia and Aeromonas allosaccharophila to Aeromonas
      veronii (Huys et al., Int. J. Syst. Bacteriol. 46, 572-580 [19961). Currently,
      two genotypically indistinguishable biovars are known to exist in the latter
      species, namely A. veronii biovar sobria and A. veronii biovar veronii. In the
      current study, new DNA-DNA hybridization experiments showed that the type strain
      of A. ichthiosmia, LMG 12645T (= DSM 6393T), and that of A. allosaccharophila,
      LMG 14059T (= CECT 4199T), were 84-96% and 78-82% related to A. veronii strain
      LMG 9075T (= ATCC 35624T), respectively. Based upon phenotypic characterization
      including a total of 151 tests, the type strain of A. ichthiosmia could be
      clearly allocated to A. veronii biovar sobria. On the other hand, the three
      strains constituting the species A. allosaccharophila were found to be
      phenotypically heterogeneous. None of these strains clearly fitted the
      biochemical description of either of the two A. veronii biovars or tightly
      clustered with any of the A. veronii reference strains. On the basis of published
      taxonomic evidence (including AFLP and phylogenetic data) and the newly reported
      results, there is compiling evidence to conclude that A. ichthiosmia Schubert et
      al. 1990 is a later synonym of A. veronii Hickman-Brenner et al. 1987. However,
      due to the lack of agreement encountered between the new DNA reassociation
      results and previously reported DNA homology and phylogenetic data, a conclusive
      proposal on the genotypic position of A. allosaccharophila should await further
      studies.

PMID- 11518321
TI  - Identification and characterization of Carnobacteria isolated from fish
      intestine.
AB  - Eleven bacterial strains were isolated from the gastrointestinal tract of four
      fish species, Atlantic salmon (Salmo salar L.), Arctic charr (Salvelinus alpinus
      L.), Atlantic cod (Gadus morhua L.) and wolffish (Anarhichas lupus L.). All the
      strains were Gram-positive rods, non-sporing, catalase and oxidase-negative, able
      to grow at pH 9.0 but not on acetate containing media (pH < or = 5.4), and were
      fermentative. They had a high content of oleic acid (18:1 n-9) in cellular lipid,
      and were found to belong to the genus Carnobacterium by phenotypic criteria. The
      eleven carnobacteria strains were further identified on the basis of 16S rDNA
      sequence analysis and AFLP(TM) fingerprinting.

PMID- 11518322
TI  - Description of two biovars in the Rhizobium galegae species: biovar orientalis
      and biovar officinalis.
AB  - Twenty-six Rhizobium galegae strains, representing the center of origin of the
      host plants Galega orientalis and G. officinalis as well as other geographic
      regions, were used in a polyphasic analysis of the relationships of R. galegae
      strains. Phage typing, lipopolysaccharide (LPS) profiling, pulsed field gel
      electrophoresis (PFGE) profiling and rep-PCR (use of repetitive sequences as PCR
      primers for genomic fingerprinting) with REP and ERIC primers investigated
      nonsymbiotic properties, whereas plasmid profiling and hybridisation with a nif
      gene probe, and with nodB, nodD, nod box and an IS sequence from the symbiotic
      region as probes, were used to reveal the relationships of symbiotic genes. The
      results were used in pairwise calculations of distances between the strains, and
      the distances were visualised as a dendrogram. Indexes of association were
      compared for all tests pooled, and for chromosomal tests and symbiotic markers
      separately, to display the input of the different categories of tests on the
      grouping of the strains. Our study shows that symbiosis related genetic traits in
      R. galegae divide strains belonging to the species into two groups, which
      correspond to strains forming an effective symbioses with G. orientalis and G.
      officinalis respectively. We therefore propose that Rhizobium galegae strains
      forming an effective symbiosis with Galega orientalis are called R. galegae bv.
      orientalis and strains forming an effective symbiosis with Galega officinalis are
      called R. galegae bv. officinalis.

PMID- 11518323
TI  - Species concepts in the Cylindrocladium floridanum and Cy. spathiphylli complexes
      (Hypocreaceae) based on multi-allelic sequence data, sexual compatibility and
      morphology.
AB  - Much attention has recently been devoted to the delimitation of species units in
      Cylindrocladium (Cy.). In this regard the present study focuses on the taxa
      within the unresolved Cy. floridanum and Cy. spathiphylli species complexes.
      Maximum parsimony analyses of DNA sequences of ITS, beta-tubulin and histone
      regions of rRNA genes, and mating experiments revealed a geographically isolated
      species of Cylindrocladium in the Cy. spathiphylli (teleomorph: Calonectria
      spathiphylli) species complex. Cy. pseudospathiphylli sp. nov. (teleomorph: Ca.
      pseudospathiphylli sp. nov.) is described as a new phylogenetic, biological and
      morphological species. It is distinguished from Cy. spathiphylli by being
      homothallic, having smaller macroconidia, and distinct DNA sequences of beta
      tubulin and histone genes. Similarly, parsimony analysis of a combined data set
      also indicated several phylogenetic species to exist within Cy. floridanum
      (teleomorph: Ca. kyotensis). Based on differences in vesicle morphology and
      conidium dimensions, the Canadian population of Cy. floridanum, formerly known as
      Cy. floridanum Group 2, is described as Cy. canadense sp. nov., while a further
      collection from Hawaii is described as Cy. pacificum sp. nov.

PMID- 11518324
TI  - Metabolic and functional properties of lactic acid bacteria in the gastro
      intestinal ecosystem: a comparative in vitro study between bacteria of intestinal
      and fermented food origin.
AB  - Metabolic and functional properties of probiotic lactic acid bacteria (LAB) in
      the human gastro-intestinal ecosystem may be related to certain beneficial health
      effects. In this study, lactobacilli of either intestinal or fermented food
      origin were compared in their capability to survive low pH and bile, in their
      metabolic activity in the presence of bile salts and mucins, as well as in their
      potential to attach to enterocyte-like CaCO-2 cells. Food fermenting bacteria
      especially strains of the species Lactobacillus plantarum showed high tolerance
      to the consecutive exposure to hydrochloric acid (pH 1.5-2.5) and cholic acid (10
      mM). Growth in and deconjugation of glycocholic (5 mM) and taurocholic acids (5
      mM), as demonstrated for all lactobacilli of intestinal origin, was detected for
      food fermenting strains of the species L. plantarum, but not L. paracasei and L.
      sakei. Degradation of mucins was not observed for lactobacilli. Adhesion to the
      intestinal epithelial cell line CaCO-2 was demonstrated for several food
      fermenting bacterial strains in vitro. Soluble factors in the spent culture
      supernatants from intestinal and fermented food lactobacilli but not
      staphylococci cross reacted and synergized with cell wall components to promote
      adhesion to CaCO-2 cells. A competitive role of fecal bacteria on the adhesion of
      lactobacilli to CaCO-2 cells was demonstrated. In conclusion we have shown that
      metabolic and functional properties of intestinal lactobacilli are also found in
      certain bacteria of fermented food origin.

PMID- 11518325
TI  - Polymerase chain reaction and denaturing gradient gel electrophoresis monitoring
      of fecal bifidobacterium populations in a prebiotic and probiotic feeding trial.
AB  - A culture-independent approach based on genus-specific PCR and denaturing
      gradient gel electrophoresis (DGGE) was used to monitor qualitative changes in
      fecal bifidobacterial communities in a human feeding trial. DNA was extracted
      directly from feces and bifidobacterial 16S rDNA sequences were amplified using
      genus-specific PCR. The PCR fragments were subsequently separated in a sequence
      specific manner by DGGE in order to obtain a profile of bifidobacterial
      fragments. The DGGE profiles revealed that in general, administration for two
      weeks of galactooligosaccharide and/or Bifidobacterium lactis Bb-12 (8 g and 3 x
      10(10) cfu per day, respectively) did not affect the qualitative composition of
      the indigenous Bifidobacterium population, while B. lactis Bb-12 transiently
      colonised the gut.

PMID- 11518326
TI  - In vitro study of prebiotic properties of levan-type exopolysaccharides from
      Lactobacilli and non-digestible carbohydrates using denaturing gradient gel
      electrophoresis.
AB  - Batch cultures inoculated with human faeces were used to study the prebiotic
      properties of levan-type exopolysaccharides (EPS) from Lactobacillus
      sanfranciscensis as well as levan, inulin, and fructooligosaccharide (FOS).
      Denaturing gradient gel electrophoresis of 16S rDNA fragments generated by PCR
      with universal primers was used to analyse the cultures. Characteristic changes
      were revealed in the composition of the gut bacteria during fermentation of the
      carbohydrates. An enrichment of Bifidobacterium spp. was found for the EPS and
      inulin but not for levan and FOS. The bifidogenic effect of the EPS was confirmed
      by culturing on selective medium. In addition, the use of EPS and FOS resulted in
      enhanced growth of Eubacterium biforme and Clostridium perfringens, respectively.

PMID- 11518327
TI  - DNA polynucleotide probes generated from representatives of the genus
      Acinetobacter and their application in fluorescence in situ hybridization of
      environmental samples.
AB  - The application of rRNA directed polynucleotide probes carrying multiple labels
      facilitates the detection of target cells by fluorescence in situ hybridizations
      and allows specific enrichment by cell fishing. So far, exclusively RNA
      transcript probes have been used. To reduce the effort in the preparation of the
      polynucleotides and to enhance their stability, DNA probes matching a part of the
      highly variable domain III on the 23S rRNA were constructed by amplification of
      the target region using PCR. Fluorescent labeling was achieved by incorporation
      of Cy3-labeled desoxyribonucleotides in the amplification. DNA polynucleotide
      probes were constructed for the seven validly described Acinetobacter species.
      Amplified domain III rDNA of A. baumannii and A. calcoaceticus could be readily
      applied as species specific probe. In addition, rDNA fragments could be used to
      recognize two groups of species, one comprising A. haemolyticus, A. junii and A.
      radioresistens and the other one A. lwoffii and A. johnsonii. Acinetobacter
      baumannii cells, some of them occurring in filaments, could be detected by in
      situ hybridization in native samples of activated sludge.

PMID- 11518328
TI  - Novel endophytes of rice form a taxonomically distinct subgroup of Serratia
      marcescens.
AB  - Six endophytic strains isolated from surface-sterilized rice roots and stems of
      different rice varieties grown in the Philippines were characterized. They were
      analyzed by physiological and biochemical tests, SDS-PAGE of whole-cell protein
      patterns, DNA-DNA hybridization and 16S rDNA sequencing. SDS-PAGE of whole-cell
      patterns showed that the six isolates fell into two subgroups which were similar
      but not identical in protein patterns to S. marcescens. The phylogenetic analysis
      of 16S rDNA sequences of two representative strains IRBG 500 and IRBG 501
      indicated that they were closely related to S. marcescens (more than 99%
      identity). Physiological and biochemical tests corroborated that the isolates
      were highly related to each other and to S. marcescens. In cluster analysis, all
      six isolates were clustered together at 93% similarity level and grouped closely
      with Serratia marcescens at 86% similarity level. DNA-DNA hybridization studies
      revealed that the isolates shared high similarity levels with S. marcescens (> or
      =86% DNA-DNA binding), indicating they belong to the same species. However, the
      isolates differed in several biochemical characteristics from the type strain.
      They produce urease and utilize urea and L(+) sorbose as a substrate, which is
      different from all known Serratia reference strains. These results suggest that
      the six endophytic isolates represent a novel, non-pigmented subgroup of S.
      marcescens.

PMID- 11518329
TI  - Isolation and characterization of a Pseudomonas putida strain able to grow with
      trimethyl-1,2-dihydroxy-propyl-ammonium as sole source of carbon, energy and
      nitrogen.
AB  - Trimethyl-1,2-dihydroxypropyl-ammonium (TM) originates from the hydrolysis of the
      parent esterquat surfactant, which is widely used as softener in fabric care.
      Based on test procedures mimicking complex biological systems, TM is supposed to
      degrade completely when reaching the environment. However, no organisms able to
      degrade TM were isolated nor has the degradation pathway been elucidated so far.
      We isolated a Gram-negative rod able to grow with TM as sole source of carbon,
      energy and nitrogen. The strain reached a maximum specific growth rate of 0.4(h
      1) when growing with TM as the sole source of carbon, energy and nitrogen. TM was
      degraded to completion and surplus nitrogen was excreted as ammonium into the
      growth medium. A high percentage of the carbon in TM (68% in continuous culture
      and 60% in batch culture) was combusted to CO2 resulting in a low yield of 0.54
      mg cell dry weight per mg carbon during continuous cultivation and 0.73 mg cell
      dry weight per mg carbon in batch cultures. Choline, a natural structurally
      related compound, served as a growth substrate, whereas a couple of similar other
      quaternary aminoalcohols also used in softeners did not. The isolated bacterium
      was identified by 165-rDNA sequencing as a strain of Pseudomonas putida with a
      difference of only one base pair to P. putida DSM 291T. Despite their high
      identity, the reference strain P. putida DSM 291T was not able to grow with TM
      and the two strains differed even in shape when growing on the same medium. This
      is the first microbial isolate able to degrade a quaternary ammonium softener
      head group to completion. Previously described strains growing on quaternary
      ammonium surfactants (decyltrimethylammonium, hexadecyltrimethylammonium and
      didecyldimethylammonium) either excreted metabolites or a consortium of bacteria
      was required for complete degradation.

PMID- 11518330
TI  - Isolation and characterisation of Rhodococcus erythropolis TA57 able to degrade
      the triazine amine product from hydrolysis of sulfonylurea pesticides in soils.
AB  - We isolated a bacterium capable of metabolising a methylated and methoxylated s
      triazine ring as the only nitrogen source. On a weight basis, the s-triazine,
      commonly named triazine amine (TAM), constitutes approx. half of several
      sulfonylurea herbicides and is formed after hydrolysis of these herbicides. The
      isolate, strain TA57 was identified using multi-phasic taxonomy as a gram
      positive Rhodococcus erythropolis. Strain TA57 mineralised over 50% 14C-labelled
      TAM within 4 days in growing cultures using all of the nitrogen for growth. The
      degradation capacity was found stable in cells grown on either tryptic soy broth
      agar plates or in minimal medium with NH4+. Among other s-triazines tested, only
      one other methylated, but de-methoxylated s-triazine amine supported growth.
      Inoculating 10(6) cells of TA57 per gram of soil (d.w.) resulted in 50%
      mineralisation of 14C labelled TAM (1 mg kg(-1)) within 25 days, in contrary to
      the indigenous population that mineralised only 6% in 50 days.

PMID- 11518331
TI  - Toxic Bacillus pumilus from indoor air, recycled paper pulp, Norway spruce, food
      poisoning outbreaks and clinical samples.
AB  - Forty-four B. pumilus isolates of food poisoning, clinical, environmental and
      industrial origins were investigated for toxin production using the boar
      spermatozoan motility assay, previously shown to be a sensitive method for
      detecting non-protein toxins from B. cereus and B. licheniformis. The three toxic
      isolates originated from live tree, indoor air and recycled paper pulp and were
      more toxic than the previously described food poisoning isolates of B.
      licheniformis, whereas the B. pumilus food poisoning and clinical isolates were
      lower in toxicity. The type strain also produced inhibitory substances. The toxic
      substances were insensitive to heat (100 degrees C, 20 min), to pH 2 or pH 10 and
      to digestion with pronase. The substances were readily soluble in methanol and
      chloroform, but less soluble in toluene. Exposure of boar spermatozoa to 1-10
      microg ml(-1) (EC50) of methanol soluble substance from the four strains
      disrupted the plasma membrane permeability barrier, induced abnormalities in the
      postacrosomal sheath, collapsed the mitochondrial and suppressed cytoplasmic NAD
      reduction. No change was observed in human peripheral blood lymphocytes exposed
      to concentrations of B. pumilus extract that affected spermatozoa. The toxin
      producing isolates were 99.4 to 99.6% similar in 16SrDNA (500 bp) to the type
      strain and could not be distinguished from the 41 non-toxic isolates by
      biochemical properties or whole cell fatty acid composition.

PMID- 11518332
TI  - Random amplified ribosomal DNA restriction analysis for rapid identification of
      thermophilic Actinomycete-like bacteria involved in hypersensitivity pneumonitis.
AB  - Hypersensitivity pneumonitis (HP) is a pulmonary disease characterised by
      inflammation that can be caused by, amongst other substances, a subset of 4
      thermophilic mycelial bacteria: Saccharopolyspora rectivirgula, Saccharomonospora
      viridis, Thermoactinomyces sacchari, and Thermoactinomyces vulgaris. Air sampling
      analyses in highly contaminated environments are often performed to evaluate
      exposure to these species which are difficult and fastidious to identify by
      conventional techniques. The aim of this study was to use amplified ribosomal DNA
      restriction analysis (ARDRA) to develop a method of identification for those
      thermophilic organisms that would be more rapid and simple. Strains of these 4
      species were obtained from the American type culture collection (ATCC) and were
      characterized using biochemical tests and ARDRA patterns obtained on their
      partial-lenght amplified 16S rDNAs. To validate this approach, ARDRA with two
      restriction enzymes, TaqI and HhaI, was applied to 49 thermophilic actinomycete
      like strains from environmental samples (sawmills). The results obtained show
      that combining some cultural characteristics and biochemical tests, such as
      xanthine or hypoxanthine decomposition, growth in the presence of NaCl, lysozyme
      or novobiocin, and spore resistance over 100 degrees C provide a rough
      identification and selection of the genera of interest. Consequently, target
      species could be confirmed by digestion of partial-lenght 16S rDNA with the use
      of Taql and HhaI restriction enzymes that gave specific restriction patterns.
      ARDRA analyses on the 49 environmental actinomycete-like organisms revealed the
      presence of 8 Saccharopolyspora rectivirgula, 2 Saccharomonospora viridis, and 15
      Thermoactinomyces vulgaris strains, the other strains had restriction patterns
      different than those of the species of interest. Results of the present study
      will be applicable to other potential HP environments such as dairy barns, peat
      bogs and compost plants.

PMID- 11518333
TI  - A highly specific one-step PCR - assay for the rapid discrimination of
      enteropathogenic Yersinia enterocolitica from pathogenic Yersinia
      pseudotuberculosis and Yersinia pestis.
AB  - Based on differences within the yopT-coding region of Yersinia. enterocolitica, Y
      pseudotuberculosis and Y pestis, a rapid and sensitive one-step polymerase chain
      reaction assay with high specificity for pathogenic Y enterocolitica was
      developed. By this method pathogenic isolates of Y enterocolitica can be easily
      identified and discriminated from other members of this genus. The entire coding
      sequence of the yopT effector gene of Y. pseudotuberculosis Y36 was determined.

PMID- 11518334
TI  - Analysis of stable low molecular weight (LMW) RNA profiles of hydrocarbon
      metabolizing bacteria by staircase electrophoresis.
AB  - Staircase electrophoresis (SCE) in polyacrilamide gels was used to analyze the
      stable low-molecular weight (LMW) RNA profiles of several propane and butane
      oxidizing bacteria belonging to different species and genera. Differences in the
      number and distribution of the RNA bands in these profiles allowed us to
      differentiate among them. Congruent results were found between the established
      classification of these bacteria and results obtained by LMW RNA profiling and
      moreover, some misclassified strains can be assigned to the correct genus and
      species using this technique. LMW RNA profiling by staircase electrophoresis,
      which makes possible the analysis of a large number of strains in a short time,
      permits rapid identification of hydrocarbon metabolizing species when compared
      with LMW RNA profiles of reference strains.

PMID- 11518335
TI  - Aeration conditions affecting growth of purple nonsulfur bacteria in an organic
      wastewater treatment process.
AB  - Effects of aeration on purple nonsulfur bacteria (PnSB) were studied in
      photobioreactors. Bacterial community changes were analyzed by denaturing
      gradient gel electrophoresis (DGGE) and fluorescence in situ hybridization
      (FISH). DGGE band pattern change was small and only few prominent bands were
      obtained at non-aeration condition. Sequencing results of the prominent DGGE
      bands obtained at this condition revealed that they represented mainly the PnSB,
      Rhodobacter sphaeroides and Rhodopseudomonas palustris. On the other hand, under
      aerated condition, some prominent bands originated from heterotrophs appeared but
      no proliferation of PnSB was observed. FISH was applied to detect PnSB and their
      population was quantified. Maximum PnSB ratio (up to 80%) was obtained both at
      non-aeration condition and at constant ORPs less than -200 mV. In the presence of
      DO, Rps. palustris was more competitive to chemoheterotrophs than Rb.
      sphaeroides.

PMID- 11518336
TI  - Identity and potential functions of heterotrophic bacterial isolates from a
      continuous-upflow fixed-bed reactor for denitrification of drinking water with
      bacterial polyester as source of carbon and electron donor.
AB  - A collection of 186 heterotrophic bacteria, isolated directly from a continuous
      upflow fixed-bed reactor for the denitrification of drinking water, in which
      poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) granules acted as biofilm
      carrier, carbon source and electron donor, was studied with regard to taxonomic
      affiliation and degradation and denitrification characteristics. Two granule
      samples were taken from a fully operating reactor for enumeration and isolation
      of heterotrophic bacteria. One sample was drawn from the lower part of the
      reactor, near the oxic zone, and the other sample from the upper, anoxic part of
      the fixed bed. Dominant colonies were isolated and the cultures were identified
      using fatty acid analysis and 16S rDNA sequencing. Their ability to degrade the
      polymer and 3-hydroxybutyrate and to denitrify in pure culture was assessed. The
      results show that high numbers of heterotrophic bacteria were present in the
      biofilms on the polymer granules, with marked differences in taxonomic
      composition and potential functions between the lower and upper part of the fixed
      bed. The majority of the isolates were Gram negative bacteria, and most of them
      were able to reduce nitrate to nitrite or to denitrify, and to utilize 3
      hydroxybutyrate as sole source of carbon. Only two groups, one identified as
      Acidovorax facilis and the other phylogenetically related to Brevundimonas
      intermedia, could combine denitrification and utilization of poly(3
      hydroxybutyrate) (PHB), and were found only in the upper sample. The other groups
      occurred either in the lower or upper part, or in both samples. They were
      assigned to Brevundimonas, Pseudomonas, Agrobacterium, Achromobacter, or
      Phyllobacterium, or were phylogenetically related to Afipia or Stenotrophomonas.

PMID- 11518337
TI  - Molecular microbial diversity of a spacecraft assembly facility.
AB  - In ongoing investigations to map and archive the microbial footprints in various
      components of the spacecraft and its accessories, we have examined the microbial
      populations of the Jet Propulsion Laboratory's Spacecraft Assembly Facility (JPL
      SAF). Witness plates made up of spacecraft materials, some painted with
      spacecraft qualified paints, were exposed for approximately 7 to 9 months at JPL
      SAF and examined the particulate materials collected for the incidence of total
      cultivable aerobic heterotrophs and heat-tolerant (80 degrees C for 15-min.)
      spore-formers. The results showed that the witness plates coated with spacecraft
      qualified paints attracted more dust particles than the non-coated stainless
      steel witness plates. Among the four paints tested, witness plates coated with
      NS43G accumulated the highest number of particles, and hence attracted more
      cultivable microbes. The conventional microbiological examination revealed that
      the JPL-SAF harbors mainly Gram-positive microbes and mostly spore-forming
      Bacillus species. Most of the isolated microbes were heat resistant to 80 degrees
      C and proliferate at 60 degrees C. The phylogenetic relationships among 23
      cultivable heat-tolerant microbes were examined using a battery of morphological,
      physiological, molecular and chemotaxonomic characterizations. By 16S rDNA
      sequence analysis, the isolates fell into seven clades: Bacillus licheniformis,
      B. pumilus, B. cereus, B. circulans, Staphylococcus capitis, Planococcus sp. and
      Micrococcus lylae. In contrast to the cultivable approach, direct DNA isolation,
      cloning and 16S rDNA sequencing analysis revealed equal representation of both
      Gram-positive and Gram-negative microorganisms.

PMID- 11518338
TI  - Perceived realism and role attractiveness in movie portrayals of alcohol
      drinking.
AB  - OBJECTIVE: To explore the role of perceived realism and role attractiveness in
      dramatized alcohol portrayals. METHODS: A total of 158 college students watched 1
      of 2 movie versions that portray alcohol drinking either positively or
      negatively. RESULTS: Role attractiveness of the drinking character increased
      favorableness in alcohol-related attitudes and dispositions in Positive
      Condition, whereas perceived realism acted as a significant mediator in Negative
      Condition. CONCLUSION: Health educators and policymakers are alerted to the fact
      that the entertainment media too often portray glamorous characters as enjoying
      alcoholic beverages without facing negative consequences, which may particularly
      affect the viewers who feel attracted to the role characters.

PMID- 11518339
TI  - The relationship between the stages of change for exercise and health insurance
      costs.
AB  - OBJECTIVE: To determine the relationship between the stages of exercise
      participation and health insurance costs. METHODS: A hurdle model was used to
      examine health survey and health insurance costs data by stage of exercise
      participation. RESULTS: Employees classified in the maintenance stage (regular
      exercisers) of exercise adoption had lower costs and a lower probability of being
      classified in the high-cost group than did employees classified in the other
      stages of change for exercise participation. CONCLUSION: This study offers
      evidence that the health insurance of individuals classified in the maintenance
      stage of exercise costs less than does that of individuals classified in other
      stages of exercise adoption.

PMID- 11518340
TI  - Using simple measures to estimate body fat percentage in college men.
AB  - OBJECTIVE: To develop a prediction equation to estimate the body fat percentage
      of young men using simple measurements. METHODS: Subjects were 150 males, age 18
      to 26 years. Self-reported lifestyle variables and measured circumferences were
      used to predict body fat percentage, assessed using hydrostatic weighing.
      RESULTS: The final model included 7 variables. The equation had a SEE of 2.66%
      and a PRESS SEE of 2.82%, and accounted for 80% of the variance in the criterion,
      body fat percentage. CONCLUSIONS: The regression equation developed in this study
      accurately estimates body fat percentage in young men by using simple,
      inexpensive measures.

PMID- 11518341
TI  - Factors related to publication productivity in a sample of female health
      educators.
AB  - OBJECTIVE: To examine factors related to success in academic publishing for women
      in health education and promotion. METHODS: Ten participants, identified as
      productive authors, submitted a copy of their curriculum vita and completed a
      questionnaire related to publishing productivity. RESULTS: Factors that
      contributed to successful publication included personal attributes, such as self
      discipline and effective time management, and situational factors, such as
      talented collaborators, access to mentoring, and grant funding. Tips for
      maximizing productivity and enhancing collaborative efforts with colleagues are
      also presented. CONCLUSION: Findings support correlates of productivity in
      faculty members that have been reported in other academic disciplines.

PMID- 11518342
TI  - Evaluating a fear appeal message to reduce alcohol use among "Greeks".
AB  - OBJECTIVE: To evaluate the impact of a fear appeal message on college students'
      drinking behavior using the extended parallel process model. METHOD: A survey was
      administered to a random sample of undergraduates (n=224) in 38 national
      fraternal organizations. RESULTS: Both perceived efficacy and perceived threat
      were significantly correlated with drinking behavior. There was a significant
      difference both in drinking behavior and attendance at alcohol-free events
      between those who heard and those who did not hear the message. CONCLUSIONS:
      Theoretically based fear appeal messages may be a useful way to promote
      responsible drinking among college students.

PMID- 11518343
TI  - Adolescent perceptions of college student drinking.
AB  - OBJECTIVE: To extend knowledge about perceived drinking norms by assessing
      perceptions of college student drinking in a sample of 7th- to 12th-graders.
      METHODS: Anonymous questionnaire was administered to 2,017 adolescents in two
      Ohio school districts. RESULTS: By seventh grade, 89.6% of the students had
      formed normative perceptions of collegiate drinking. A canonical correlation
      analysis revealed that perceptions of collegiate drinking have substantial,
      independent relationships not only with alcohol use intensity and drinking onset,
      but also with indicators of tobacco and other drug use as well. CONCLUSIONS:
      Exaggerated perceptions of college student drinking are psychosocial markers of
      substance use in 7th- to 12th-graders.

PMID- 11518344
TI  - Surgical treatment of Graves orbitopathy: a modified balanced technique.
AB  - Surgery has a definite place in the treatment of the exophthalmos in Graves
      orbitopathy. Thirty-two patients with Graves orbitopathy were operated on. Twenty
      patients received a three-wall orbital decompression. Five patients received a
      two-wall orbital decompression with lipectomy and seven patients underwent a two
      wall orbital decompression combined with an advancement osteotomy of the supra-,
      lateral- and infra-orbital rim and a lipectomy. In cases with Hertel values less
      than 25 mm, the two-wall orbital decompression with removal of orbital fat. and
      in cases with Hertel values more than 25 mm, the two-wall orbital decompression
      with lipectomy and an advancement osteostomy of the supra-, lateral- and
      infraorbital rim is the treatment of choice.

PMID- 11518345
TI  - A radiographic analysis of computer prediction in conjunction with orthognathic
      surgery.
AB  - This retrospective study analysed the accuracy and reliability of predictions
      generated in patients treated with orthognathic surgery by comparing Quick Ceph
      Image software (Quick Ceph Image Pro version 3.0) predictions with post-surgical
      lateral cephalographs. Pre- and post-surgical lateral cephalographs of 28 adult
      patients (12 males and 16 females) were scanned into the computer and 28
      landmarks were identified and digitized. Digitization error was assessed from
      repeated digitization. Fourteen measurements of the predicted and actual
      postsurgical hard tissue landmarks were compared using Student's t-test. Results
      showed a good correlation between repeated digitization for all measurements.
      Student's t-test indicated that 10 of the 14 measurements showed no statistically
      significant differences. Only the ANB (P=0.008), FMA (P=0.001), SN-Mxl (P=0.03)
      and Wit's (P=0.0001) showed statistically significant differences between the
      predicted and actual measurements. However only the Wit's showed clinical
      significant differences between the two measurements. Caution still must remain
      as the surgeon may not achieve his planned position in an individual patient. In
      some cultures there may also be medico-legal implications of these predictions.

PMID- 11518346
TI  - A classification and characterization of skeletal class III malocclusion on etio
      pathogenic basis.
AB  - Skeletal Class III malocclusion has been classified by the position of the
      maxilla, the mandible, the maxillary alveolus, the mandibular alveolus and
      vertical development. This morphologic approach is simple and useful for clinical
      use, but it is insufficient to permit understanding of the pathophysiology of
      dysmorphoses. The authors hypothesized that there were different patterns of
      mutual relation of the skeletal components contributed to pathologic equilibrium
      of skeletal Class III malocclusion. The purpose of this study is 3-fold; (1) to
      classify skeletal Class III malocclusion in subgroups that can show the
      architectural characteristics of the deformity, (2) to analyze the craniofacial
      architecture of each subgroup on etio-pathogenic basis, and (3) to characterize
      and visualize the pattern as a prototype. Materials used in this study were
      lateral cephalograms of 106 untreated skeletal Class III malocclusion adults,
      which were analyzed with modified Delaire's analysis. Linear and angular
      measurements of each subject were obtained and cluster analysis was used for
      grouping. In the results, seven groups were identified and presented as
      prototypes, which could show the etio-pathology of the skeletal architecture. The
      classification and description presented in this study is thought to be biologic
      and helpful in the understanding of skeletal Class III malocclusion and treatment
      planning.

PMID- 11518347
TI  - Midfacial degloving: an alternative approach for traumatic corrections in the
      midface.
AB  - Midfacial degloving was used as an approach in 14 patients to correct post
      traumatic deformities in the midface. In eight patients, deformities in the naso
      orbito-ethmoid region were corrected by orbitonasal osteotomy, telecanthus
      correction, orbital grafting and nasal augmentation procedures. Zygomatic
      osteotomies were performed in five patients with orbitozygomatic deformity. In
      one patient, a midface fracture (Le Fort II/III) was reconstructed after
      midfacial degloving. By combination of transoral vestibular, intranasal and
      preseptal transconjunctival incisions a complete degloving of the midface up to
      the nasofrontal angle and the zygoma prominence was possible. All osteotomies
      could be completed after midfacial degloving. Additional coronal incisions were
      not required. Orbitonasal osteotomies for nasal lengthening as well as fixation
      of the medial canthal ligament by a miniplate could be performed under direct
      vision. There were no postoperative complications such as stenosis of the nasal
      aperture or disturbances of the mimic musculature. Midfacial degloving offers
      good exposure, specially of the central part of the midface, without leaving an
      external scar. It is useful for reconstructive procedures in patients after
      midface trauma.

PMID- 11518348
TI  - Effectiveness of operative treatment of internal orbital wall fracture with
      polydioxanone implant.
AB  - Many implants, some made from teflon or silicone, have been used for internal
      orbital wall reconstruction. Late complications relating to use of such implants
      have been reported. In this prospective study a polydioxanone (PDS) implant
      absorbable in vivo was used for internal orbital wall reconstruction. Follow-up
      involved clinical examination, magnetic resonance imaging (MRI) and computerized
      tomography (CT). Clinical examinations were undertaken before operation and up to
      36 weeks postoperatively. Sixteen consecutive patients (10 pure blow-out
      fractures, six with associated zygomatic fracture) took part in the study.
      Prevalences of diplopia, proptosis and enophthalmus were recorded during each
      follow-up examination. This study revealed no muscle entrapment within the
      fracture line. Although CT results confirmed bone growth in the internal orbital
      wall, shape was unsatisfactory, and orbital volume was not reduced. MRI revealed
      thick scar formations in six cases (37.5%), fibrotic sinuses filled with air or
      gas in three cases (19%) and a fibrotic sinus with fluid around the PDS in one
      case (6%). Our results suggest that use of PDS in reconstructing the internal
      orbital wall is inadvisable.

PMID- 11518349
TI  - Retrospective analysis of 1502 patients with facial fractures.
AB  - A total of 1502 patients with facial fractures treated between 1981 and 1996 were
      retrospectively analysed. The male: female ratio was 2.8:1 and the largest
      subgroup of patients was between 10 and 29 years of age. The most common cause of
      injury was traffic accidents (52%) involving motorcycles, bicycles or
      automobiles. Other common causes included, in descending order, falls (16.6%),
      assaults (15.5%) and sports (9.7%). Isolated mandibular fractures were most
      common (56.9%), followed by isolated midface fractures (25.9%). The percentage of
      fractures involving both the midface and mandible was 6.7, and that of isolated
      alveolar fractures was 10.5.

PMID- 11518350
TI  - Aetiology and incidence of facial fractures sustained during sports: a
      prospective study of 140 patients.
AB  - A prospective study was carried out involving patients presenting with facial
      fractures sustained during sports. One hundred and forty patients were admitted
      to the Pitie-Salpetriere University Hospital of Paris between March 1998 and
      March 2000, accounting for 13.3% of all patients with facial bone fractures. The
      ratio of males to females was 7.2:1 and the mean age was 28.5 years. The majority
      of accidents occurred during soccer (25.0%), followed by rugby (15.0%), and as a
      consequence of collisions between players (50.7%). The majority of the injuries
      involved the mandible (34.4%), the zygomatic bone (23.4%) and the nasal bone
      (15.6%). The sporting activities were classified as either contact or non-contact
      sports. Frontal sinus, central midface and LeFort fractures were seen more often
      in vehicular sports such as mountainbiking and skiing. The authors stress the
      importance of preventive measures, including the use of protective equipment,
      periodic sports medical check-ups and personal discipline.

PMID- 11518351
TI  - MRI examination of the TMJ after surgical treatment of condylar fractures.
AB  - The position of discs in 20 adult patients whose unilateral condylar fractures
      were treated by open reduction was investigated by means of magnetic resonance
      imaging. In four (20%) of the 20 cases, the disc was anteriorly displaced in both
      the closed mouth and open mouth positions. Three of the four cases had a high
      condylar neck fracture with dislocation and one had a high condylar neck fracture
      with displacement. The results of this study showed that repositioning the
      dislocated condyle did not always lead to anatomical restoration of the joint
      structures.

PMID- 11518352
TI  - The mandibular condyle in juvenile chronic arthritis patients with mandibular
      hypoplasia: a clinical and histological study.
AB  - In 12 JCA patients with severe mandibular hypoplasia, who all strongly demanded
      early treatment, 21 mandibular condyles were replaced by costochondral grafts.
      All of them had radiographic morphological changes in the mandibular condyles
      with varying degrees of destruction of the articular cartilages. Severe
      pathological changes in the lower joint compartments were consistently observed
      at surgery. Hence, the lower joint compartments were obstructed with
      granulomatous tissue, whereas the upper compartments were without macroscopic
      pathological changes. These findings indicated a polarized involvement of the
      temporomandibular joint (TMJ) in juvenile chronic arthritis (JCA). The extent of
      condylar articular surface destruction at histological examination varied from
      focal to total cartilage destruction. Inflammation of the subchondral bone marrow
      was a frequent finding. In spite of considerable arthritic destruction of the
      condyles, only one patient had TMJ pain, while a restricted mouth opening
      capacity was a more frequent finding. Thus, TMJ pain did not seem to constitute a
      reliable symptom of serious arthritic destruction of the mandibular condyle.

PMID- 11518353
TI  - Sensory impairment of the lingual and inferior alveolar nerves following removal
      of impacted mandibular third molars.
AB  - In a prospective study 1,106 impacted mandibular third molars were removed from
      687 patients. Clinical, radiographic, and surgical factors were recorded.
      Postoperatively, we examined the modalities of common sensation in order to
      assess sensory deficit. The patients were followed up, until complete restitution
      occurred, or, if the sensibility failed to recover, for at least 6 months. A
      total of 3.6% of the operated sides demonstrated impairment of labial sensation,
      and 2.1% of lingual sensation. The vast majority of these disturbances subsided
      completely during the follow-up period. The incidence of persisting sensory
      diminution after 6 months was 0.91% for the inferior alveolar, and 0.37% for the
      lingual nerve. However, the degree of the persisting deficit was slight in most
      instances. The relationship between the recorded factors and the alteration of
      sensation was analysed by using the chi2 test. For the inferior alveolar nerve we
      found the patient's age, the development of the roots, the degree of impaction,
      and the radiographic position of the nerve canal to be significantly correlated
      to sensory deficit, as well as the surgical procedures in the depth of the socket
      and the intraoperative opening of the mandibular canal. As far as the lingual
      nerve is concerned, general anaesthesia and the individual operator were the main
      factors predictive of nerve damage.

PMID- 11518354
TI  - Disodium clodronate in the treatment of diffuse sclerosing osteomyelitis (DSO) of
      the mandible.
AB  - Diffuse sclerosing osteomyelitis (DSO) of the mandible is a chronic condition,
      the cause of which is not known. Jaw pain, occurring irregularly, is a typical
      symptom. The aim of the study was to assess the effectiveness of disodium
      clodronate for relieving pain in patients with DSO. Disodium clodronate is a
      bisphosphonate used to treat diseases of bone and calcium metabolism. Ten DSO
      patients experiencing pain received disodium clodronate or placebo intravenously
      on a randomized double-blind basis. Both minimum (300 mg) and maximum (900 mg)
      doses were well tolerated. Disodium clodronate administration did not result in
      better immediate pain relief than placebo administration. However, 6 months after
      treatment there was a statistically significant difference in pain intensity
      between the groups, with the disodium clodronate group experiencing significantly
      less pain.

PMID- 11518355
TI  - Oral proliferative verrucous leukoplakia (PVL); open trial of surgery compared
      with combined therapy using surgery and methisoprinol in papillomavirus-related
      PVL.
AB  - Proliferative verrucous leukoplakia (PVL) is a unique oral white lesion in which
      human papillomavirus (HPV) may play a role. PVL behaves far more aggressively
      than other forms of leukoplakia with a high rate of recurrence after surgical
      excision, and relentless progression to verrucous hyperplasia and to verrucous or
      squamous cell carcinomas. The treatment of PVL is usually by surgery, but there
      is often early recurrence. This study was an open trial of surgery in 25 patients
      with oral HPV-positive PVL, compared with combined therapy using surgery and
      methisoprinol in another group of 25 patients with oral PVL. Six months
      postoperatively there was a significant difference, with 18 recurrences in the
      patients treated by surgery alone compared to only two recurrences in the
      patients treated also with methisoprinol (isoprinosine or inosine pranobex), a
      synthetic agent with immunomodulatory properties and some antiviral activity
      against HPV. Eighteen months postoperatively there were no further recurrences in
      the patients treated by surgery alone but another two recurrences in the patients
      treated with methisoprinol. Overall, by 18 months follow-up, there were 18
      recurrences in the group treated by surgery alone, compared with four in those
      also receiving methisoprinol. The use of this antiviral agent appeared to offer a
      significant enhancement to the surgical management of PVL.

PMID- 11518356
TI  - Activities of plasminogen activator, plasmin and kallikrein in synovial fluid
      from patients with temporomandibular joint disorders.
AB  - To measure the activities of plasminogen activator (PA), plasmin and kallikrein,
      multiple synovial fluid samples were taken from 32 patients with internal
      derangement (ID) and osteoarthrosis (OA), and nine asymptomatic volunteers. The
      enzyme activity in synovial fluid from the temporomandibular joint (TMJ) was
      quantitated by a fluorogenic substrate assay using an enzyme substrate. In fluid
      samples from the patient group, PA was detected in 24 (31.5%), plasmin in 20
      (26.3%) and kallikrein in 53 (96.4%), while none of these enzymes were found in
      the synovial fluid samples from the control group. There were positive
      correlations found among PA, plasmin and kallikrein. These results clearly
      demonstrated increased levels of PA, plasmin and kallikrein activities in the
      synovial fluid of patients with ID and OA, and suggest that these enzymes may be
      involved in the pathogenesis of synovitis, as well as the resorption of cartilage
      and bone in TMJ.

PMID- 11518357
TI  - Topographical anatomy of the fibula and peroneal artery in Koreans.
AB  - Vascularized fibula flaps have many advantages in the restoration of the contour
      and function of the mandible. Potential disadvantages include, unreliable skin
      paddle and the limited volume of the fibula. This study was designed, to clarify
      the anatomy of the peroneal artery to the fibula and lateral leg skin, and to
      measure the dimensions of the fibula available for dental implant placement in
      Korean. Through the dissection of 63 legs of Korean cadavers, we demonstrated
      that in most cases the musculoperiosteal (mp) and septocutaneous (sc) branches of
      the peroneal artery were distributed at the middle and lower thirds of the
      fibula. There were double the number of mp perforators to the skin compared to sc
      branches. This indicates the inclusion of a generous > 1 cm cuff of Peroneous
      longus and flexor hallucis longus (FHL) in the distal and middle third of the
      fibula. The location of the nutrient foramen was just proximal to the midpoint.
      Thus, a 15-20 cm length of the fibula is available in Koreans and an 8 12 mm
      length of implant can be placed to the fibula, which provides sufficient bone to
      reconstruct a large mandibular defect.

PMID- 11518358
TI  - Anatomic position of the lingual nerve in the mandibular third molar region with
      special consideration of an atrophied mandibular crest: an anatomical study.
AB  - The position of the lingual nerve in the mandibular third molar region was
      measured and documented in 68 cadaver dissections (34 adult cadaver heads). In
      8.8% of the dissections, the lingual nerve was found at or above the level of the
      alveolar crest. In the horizontal plane, the nerve contacted the lingual plate of
      the third molar in 57.4% of the specimens. There was also a significant
      relationship between the degree of mandibular crest atrophy and the distance from
      the nerve to the molar region. The distance decreased with the degree of atrophy.
      There was no significant difference between the two sides of the head. These
      results demonstrate the vulnerability of the lingual nerve as it medially passes
      the mandibular third molar and may help avoid lingual damage during surgery in
      the third molar and retromolar region of the mandible.

PMID- 11518359
TI  - Endoscopically assisted intraoral mandibular distraction osteogenesis.
AB  - Correct placement of intraoral devices for mandibular distraction osteogenesis is
      important to achieve the ideal vector of distraction. As visual inspection and
      intraoperative management in the inferior mandibular border or at the posterior
      ascending ramus is impaired, an endoscopically assisted method is presented.
      Since the introduction of this new technique operation time and ease have been
      significantly improved.

PMID- 11518360
TI  - A simple method for medial canthal reconstruction.
AB  - A simple method for medical canthal wiring reconstruction with the help of a
      homolaterally fixed osteosynthesis plate and a metal wire is presented. This
      avoids transnasal wiring and gives superior control when correcting the position
      of the lacerated Omedial canthus.

PMID- 11518361
TI  - Surgical reconstruction of the temporomandibular joint for chronic subluxation
      and dislocation.
AB  - This paper describes the use of an inferiorly based pedicled flap from the
      temporal fascia sutured to the anterior-lateral wall of the capsule and
      augmentation of the zygomatic root of the temporal bone by a bone graft from the
      iliac crest to prevent forward movement of the condyle beyond the eminence. It
      may be used for treatment of patients with chronic subluxation and dislocation of
      the temporomandibular joint.

PMID- 11518362
TI  - Primary intraosseous carcinoma of the jaw: pooled analysis of world literature
      and report of two new cases.
AB  - Primary intraosseous carcinoma (PIOC) is a rare malignant neoplasm of the jaw.
      These tumours are believed to arise from the odontogenic epithelium and hence are
      also referred to as odontogenic carcinoma. A detailed search was made for
      squamous cell PIOC of the jaw in English literature using Medline Cancer CD. The
      data obtained were transferred onto dBase software. Two detailed case reports of
      patients treated at Regional Cancer Centre, Trivandrum during 1996 and 1997 were
      also included. A pooled analysis was carried out. Survival analysis was carried
      out using Kaplan-Meier method and log-rank statistics were used for comparing
      survival. A total of 35 cases were analysed, of which 33 were from published
      literature. The mean age of the patients at the time of diagnosis was 52.3 years
      with male to female ratio being 2.5:1. Posterior mandible was the predominant
      site. The median follow-up time was 28 months. Overall survival at 5 years was
      37.8% (95% CI; 14.8-61.0) while the corresponding disease free survival was 29.8%
      (95% CI; 9.2-54.1). Primary intraosseous carcinoma is a rare tumour of jawbones,
      characterized by progressive swelling of the jaw, pain and loosening of tooth.
      The tumour is locally aggressive and metastasizes to regional nodes. The overall
      and disease free survival is poor with almost 50% patients failing loco
      regionally within the first 2 years of follow-up.

PMID- 11518363
TI  - The effects on teeth of radiotherapy for nasal endodermal sinus tumor (yolk sac
      tumor) in childhood.
AB  - A rare case of a 10-year-old girl with an endodermal sinus tumor that occurred in
      the nasal cavity is presented. She received chemotherapy and radiotherapy at the
      age of 4. The subsequent abnormal development of the maxillary teeth is described
      and discussed in the light of the known effects of radiotherapy.

PMID- 11518364
TI  - Langerhans cell granulomatosis: a case report of polyostotic manifestation in the
      jaw.
AB  - We report the case of a 43-year-old woman who suffered from a polyostotic form of
      Langerhans cell granulomatosis (LCG) in the mandible and maxilla. The course of
      the disease was followed for more than 14 years. The disease's progression
      finally required subtotal resection of the mandible and reconstruction with a
      microvascular fibula graft. The literature is reviewed for diagnostic and
      treatment concepts based on the different stages of LCG.

PMID- 11518365
TI  - Long-term results of nonsurgical management of condylar fracture in children.

PMID- 11518366
TI  - 51st Annual Meeting of Arbeitsgemeinschaft fur Kieferchirurgie in conjunction
      with Arbeitskreis Oralpathologie und Oralmedizin and with Arbeitskreis fur
      Forensische Odonto-stomatologie all with the German Dental Association (Deutsche
      Gesellschaft fur Zahn-, Mund- und Kieferheilkunde).

PMID- 11518367
TI  - The role of regurgitation and other symptoms of reflux disease in palatal dental
      erosion; an audit project.

PMID- 11518368
TI  - Effectiveness of laparoscopic fundoplication for gastro-oesophageal reflux.
AB  - BACKGROUND: Gastro-oesophageal reflux (GERD) is a common condition. Many patients
      respond to conservative therapy. Severe symptomatic cases and those who fail
      medical treatment are referred to surgery. The long-term results of open
      fundoplication surgery have been good with a more than 90% response after 10
      years of follow-up. The introduction of laparoscopic fundoplication achieved the
      same results with shorter hospital stay, a better cosmetic result and less cost
      to the health care providers. PATIENTS AND METHODS: 74 patients who failed
      medical treatment for GERD were treated by laparoscopic fundoplication. The
      Toupet procedure was performed in 66 of these patients, the others patients had a
      Nissen-type fundoplication. The patients were followed up for a mean period (+/-
      SD) of 14.8 +/- 8.8 months (range 3-33 months). RESULTS: Most of the patients
      were males (n = 65). The mean age (+/- SD) of all the patients was 36.1 +/- 9.5
      years (range 17-60 years). The majority (93.8%) reported disappearance of
      symptoms and are not using any antireflux medications. Five patients (6.7%) are
      considered failures of the procedures. Of these, three patients developed
      recurrence of reflux symptoms during the follow-up period. The other two patients
      developed complications, i.e. gas bloat, persistent vomiting and dysphagia which
      warranted taking down the wraps laparoscopically. Two patients developed a small
      incisional hernia at the site of the 10 mm port. The mean of hospital stay (+/-
      SD) was 3.1 +/- 1.3 days (range 1-7 days). CONCLUSION: Laparoscopic
      fundoplication is safe and effectively relieves reflux symptoms in patients who
      fail medical treatment.

PMID- 11518369
TI  - The effect of different immunosuppressants on alloantigen dependent and
      independent factors involved in the development of chronic rejection in an animal
      model.
AB  - The aim of this study was to compare the effects of cyclosporine, tacrolimus,
      mycophenolate mofetil and SDZ RAD on an animal model of transplant
      arteriosclerosis involving alloantigen dependent and independent mechanisms.

PMID- 11518370
TI  - Ureteric stenting for repair of accidental ureteric injuries.
AB  - Intra-operative injury to the ureter is a well known but fortunately uncommon
      complication of any major pelvic surgical procedure. If recognised on table, it
      can be repaired by either a substitution ureteroplasty or end-to-end anatomical
      repair depending upon the extent of tissue loss. Either of these anastomoses
      could be secured by total internal stent placement. We describe an improvised
      technique of intra-operative open ureteric stenting particularly when
      radiological assistance is not available, i.e. during emergency situations.

PMID- 11518371
TI  - Defunctioning loop ileostomy and stapled side-to-side closure has low morbidity.
AB  - INTRODUCTION: Low pelvic anastomoses are associated with a high leak rate.
      Therefore, defunctioning loop ileostomies are being increasingly fashioned to
      protect against the consequences of a leak. However, the reported complication
      rates of such stoma creation and closure is between 5.7-69%. AIMS: To determine
      the outcome associated with construction and side-to-side closure of loop
      ileostomies in one specialist unit. PATIENTS AND METHODS: Data were obtained from
      a computer audit and case note analysis. RESULTS: Between 1994 and 1998, 71
      patients (41 M, 30 F) with a median age of 51 years (range 19-88 years) had a
      loop ileostomy constructed for: (i) 26 ileoanal pouches; (ii) 36 left colonic and
      rectal resections; and (iii) 9 for other reasons. Side-to-side stoma closure was
      achieved using a GIA linear stapler through a parastomal incision. The median
      hospital stay following stoma creation was 12 days (range 7-63 days) and stoma
      closure was 7 days (range 6-16 days). The median time to closure was 140 days
      (range 10-790 days). There were no ileostomy-related deaths. There were 10
      (13.8%) ileostomy-related complications, 4 following creation and 6 following
      closure. CONCLUSIONS: Loop ileostomy is easy to create and close and is
      associated with a low morbidity. Therefore, we recommend a defunctioning
      ileostomy as a procedure of choice for temporary faecal diversion for complex
      colorectal surgery.

PMID- 11518372
TI  - Adrenal masses: the investigation and management of adrenal incidentalomas.
AB  - Most general surgeons will face at sometime in their career an 'incidentaloma' of
      the adrenal gland. How should a surgeon approach an incidentaloma found during
      routine investigation for other unrelated disease processes? This paper discusses
      the investigation and management of adrenal incidentalomas and includes
      guidelines for the non-specialist.

PMID- 11518373
TI  - Acute endovascular treatment by coil embolisation of ruptured intracranial
      aneurysms.
AB  - Over 5 years, 317 consecutive patients were treated by coil embolisation within
      30 days of aneurysm rupture. Neurological deteriorations were recorded in 35
      patients during the first 48 h after treatment. In 21 patients these were due to
      procedural complications, which occurred in 31 procedures (9.8%). The timing of
      treatment relative to the last subarachnoid haemorrhage (SAH) was compared in
      patients treated after 0-2, 3-7, 8-14 and 15-30 days. No correlation was found in
      the incidence of such deteriorations and treatment periods, nor with patient's
      outcomes at 6 months. However, patients treated within 6 days of SAH had better
      outcomes than those treated later. Patients should, therefore, be treated as soon
      as possible after presentation since the technique appears less susceptible to
      the adverse effects of vasospasm in the 3-10 day period after SAH.

PMID- 11518374
TI  - Which primary shoulder and elbow replacement? A review of the results of
      prostheses available in the UK.
AB  - To assist surgeons select a suitable prosthesis, we have undertaken a detailed
      review of all shoulder and elbow replacements currently marketed in the UK.
      Twenty shoulder and 8 elbow implants, manufactured by 16 companies, have been
      identified. Twelve of the shoulder and one of the elbow implants have been
      introduced or modified in the last 8 years and have no clinical results published
      in peer-reviewed journals. Only the Biomodular, Bipolar, Copeland, Isoelastic,
      Neer hemi, Neer II, Roper-Day and Select shoulders accounting for less than 40%
      of the UK shoulder market, possess published results. The Capitello-condylar,
      Coonrad-Morrey, GSB III, Kudo, Liverpool, Roper-Tuke and Souter-Strathclyde
      elbows all have published results. These account for over 95% of all UK elbow
      replacements. The implications of these findings in an era of evidence-based
      medicine is discussed. Reviewing the clinical results should be of primary
      importance in the selection of a suitable prosthesis. Implants with a proven long
      term record must represent the 'gold standard'. New or modified implants should
      only be used if they are part of a properly conducted clinical trial.

PMID- 11518375
TI  - Are hospital surgical consultants computer literate?
AB  - Computers play an essential role in the practice of medicine and the acquisition
      of computer knowledge has, therefore, become essential in modern-day practice in
      the NHS.

PMID- 11518376
TI  - Obesity predisposes to increased drainage following axillary node clearance: a
      prospective audit.
AB  - BACKGROUND: Whilst sentinel node biopsy is being evaluated for optimising
      treatment of the axilla, axillary dissection remains the gold standard. Seroma
      formation, a common sequel to axillary dissection, has been shown to be
      associated with an increased incidence of wound infection, delayed healing, and
      lymphoedema. This study was conducted to evaluate the possible contributory role
      of obesity in axillary drainage following lymphatic dissection. PATIENTS AND
      METHODS: This study comprised a prospective review of all patients undergoing
      axillary dissection in conjunction with mastectomy or wide local excision. The
      total in-patient axillary drainage and the average daily drainage was correlated
      with various clinical parameters, including obesity, type of surgery, level of
      axillary dissection and nodal involvement. The body mass index (BMI) was used as
      a measure of obesity. RESULTS: During a 6-month period, axillary dissection was
      performed in 79 women. Nineteen patients were excluded. Patey mastectomy was
      performed on 33 (55%) and the remaining had breast conservation. The amount or
      duration of axillary drainage did not correlate with the type of operation,
      tumour histology, level of axillary dissection or the nodal status. Higher BMI
      correlated with increased mean daily axillary drainage and total volume drained,
      whilst in hospital. (Spearman correlation coefficient 0.42; P < 0.01).
      CONCLUSION: Obesity predisposes to increased axillary drainage following nodal
      clearance.

PMID- 11518377
TI  - Complications following re-exploration of the groin for recurrent varicose veins.
AB  - BACKGROUND: Groin surgery for recurrent varicose veins can be technically
      difficult due to scarring from previous surgery. Access to the sapheno-femoral
      junction (SFJ) can be facilitated by approaching the veins indirectly
      (subfascially) by first exposing the common femoral artery. The aim of this paper
      was to document experience with both direct and indirect approaches to the SFJ
      for recurrent varicose veins. METHOD: A retrospective analysis of all patients
      having groin surgery for recurrent varicose veins. RESULTS: Of 128 legs having
      surgery, the approach to the SFJ was direct in 46%, indirect in 53% and unknown
      in one leg. Complications occurred after 40% of all procedures but were
      significantly more common following indirect surgery (57% versus 20%, P < 0.001),
      of which the most frequent were of a lymphatic nature (26% versus 5%, P < 0.001)
      or wound infection (16% versus 7%, P = 0.05). CONCLUSION: Wound complications are
      common following groin surgery for recurrent varicose veins especially after an
      indirect approach to the SFJ.

PMID- 11518378
TI  - Get knotted!

PMID- 11518379
TI  - Mismatch between general surgical trainees' sub-specialist interests and
      advertised jobs: a cause for concern?
AB  - The main aim of this study was to establish the primary sub-specialist interest
      of a group of senior general surgical trainees and compare these results with the
      required sub-specialist interests in consultant vacancies advertised in the
      British Medical Journal between 3.1.98 and 25.12.99. Colorectal surgery was the
      most popular sub-specialty amongst trainees (29.4%) followed by upper
      gastrointestinal/hepato-pancreato-biliary (UGI/HPB) (27.2%) and vascular surgery
      (24.3%). The least popular sub-specialties were breast/endocrine (11.4%) and
      transplant (2.9%). A total of 324 consultant jobs were advertised, with the sub
      specialist interest required as follows: Colorectal (25.6%), breast/endocrine
      (23.5%), vascular (20.4%), UGI/HPB (12%) and transplant (5.6%). Although this
      study only covers a two-year period, there are obvious discrepancies between
      trainees' sub-specialist interests and consultant vacancies. Whilst the jobs to
      trainees ratios are well matched in colorectal and vascular surgery, it appears
      that there are not enough transplant or breast trainees and too many UGI/HPB
      trainees for the number of jobs available. This problem needs urgent attention to
      avoid service shortfalls in unpopular sub-specialties and to avoid training
      people for jobs that do not exist.

PMID- 11518380
TI  - A rare and serious consequence of a rat bite.
AB  - Contact with rat saliva or faeces can lead to infection with Streptobacillus
      moniliformis and the condition known as 'rat bite fever'. We report a case of
      septic arthritis of the hip due to this organism following a bite on the finger
      of a 14-year-old boy from a rat for sale in a pet shop. The case was successfully
      treated by arthrotomy, drainage and joint lavage followed by administration of
      penicillin. Septic arthritis of the hip due to S. moniliformis has not been
      previously described and this case highlights a possible danger of keeping rats
      as pets.

PMID- 11518381
TI  - Ventriculo-peritoneal shunt and breast carcinoma.
AB  - Ventriculo-peritoneal (V-P) shunt is a frequently performed surgical procedure
      for treating hydrocephalus. The incidence of breast carcinoma in the UK is 20,000
      cases per year. We present a case of a patient with breast carcinoma in
      association with V-P shunt.

PMID- 11518382
TI  - Long-term DNA survival in ethanol-preserved archival material.

PMID- 11518383
TI  - Topical adhesive as a wound dressing for elective abdominal surgery.
AB  - The choice of wound dressing after abdominal surgery is not always easy. We
      describe a simple technique using acyanoacrylate wound adhesive to provide a
      water resistant, flexible, sealed dressing which is simple to use, requires no
      nursing time to 'maintain' and is particularly useful in the presence of stomas
      or open drains.

PMID- 11518384
TI  - Clinical and hand-held Doppler examination of primary varicose veins.

PMID- 11518386
TI  - Is current information available useful for patients and their families?
AB  - Internet has recently evolved as a versatile and influential repository of
      information including those pertaining to neurosurgery. This study was undertaken
      to find out whether there is good quality information currently available on the
      Internet for neurosurgery patients and their families. We surveyed the World Wide
      Web (www) for information on 5 neurosurgery-terms: pallidotomy, lumbar
      discectomy, hydrocephlus, glioma and carotid artery aneurysm. We searched the www
      using Google search-engine for documents related to each of the above terms and
      then assessed the information contained in the first 30-hits for each term using
      a simple 4-point grading system. Our study suggests that there is generally a
      good quantity of good quality information on the Internet for neurosurgery
      patients and their families. Internet provides an opportunity for patient
      associations and professional bodies to collaborate to create useful databases to
      help neurosurgery patients and their relatives.

PMID- 11518387
TI  - Complications of percutaneous gastrostomy in patients with head and neck cancer-
      an analysis of 42 consecutive patients.

PMID- 11518388
TI  - A useful mnemonic for severity stratification in acute pancreatitis.

PMID- 11518389
TI  - Deterioration of theatre discipline during total joint replacement--have theatre
      protocols been abandoned?

PMID- 11518390
TI  - The presence of the ail gene in clinical strains of Yersinia enterocolitica
      isolated from stools in Poland and characteristics of gene variant.
AB  - The non-American variant of ail gene was found independently of the virulence
      associated plasmid pYV in all 152 tested clinical Y. enterocolitica O:3 strains
      isolated from humans in Poland. Data obtained by sequencing exhibited high
      genetic stability of the ail gene present in the tested isolates obtained from
      different regions of the country. The PCR-RFLP technique was sufficient for fast
      identification and characterization of the ail gene variant present in the tested
      strains.

PMID- 11518391
TI  - Heat resistance and growth of Salmonella enteritidis, Listeria monocytogenes and
      Aeromonas hydrophila in whole liquid egg.
AB  - Salmonella enteritidis ATCC,13067, Listeria monocytogenes ATCC,19116 and
      Aeromonas hydrophila ATCC,7965 strains were evaluated for growth and thermal
      resistance in liquid whole egg (LWE). Each strain grew well in LWE at
      temperatures between 4 and 30 degrees C, except S. enteritidis which grew weakly
      at 4 and 10 degrees C. Maximum populations for each strain increased with
      increasing growth temperature. The thermal destruction of each strain was
      determined in six liquid products. The egg products used were LWE, LWE with 5, 10
      and 15% NaCl and LWE with 5 and 10% sucrose. L. monocytogenes tended to be more
      heat resistant than S. enteritidis and A. hydrophila. The highest kill rates were
      noted in LWE, while survival was best in those products supplemented with NaCl.
      Radiation D10 values of strains in LWE were 0.18, 0.39 and 0.49 kGy for A.
      hydrophila, S. enteritidis and L. monocytogenes, respectively.

PMID- 11518392
TI  - The DNA probe and PCR assay as useful tools to control an acid fast bacteria
      dependent biotechnological process.
AB  - Specific DNA probe has been developed for fast-growing, mycobacterial mutants
      able to selectively biotransform side chain of plant sterols. The PCR assay,
      using primers complementary to the sequence of the probe, was shown to
      distinguish biotechnological mutants from other fast-growing mycobacteria.
      Moreover, the species identification of biotechnological strains was done using
      PCR-restriction analysis based on amplification and digestion of the inner part
      of hsp65 gene (PRA-assay) as well as 16S rRNA sequencing.

PMID- 11518393
TI  - Optimization of process parameters for the continuous ethanol production by
      Kluyveromyces lactis immobilized cells in hydrogel copolymer carrier.
AB  - In the present study the optimized parameters for highest ethanol productivity by
      Kluyveromyces lactis immobilized cells bioreactor were obtained using the method
      of Lagrange multipliers. Immobilized growing yeast cells in PVA: HEMA (7%: 10%,
      w/w) hydrogel copolymer carrier produced by radiation polymerization were used in
      a packed-bed column reactor for the continuous production of ethanol from lactose
      at different levels of concentrations (50, 100 and 150) gL(-1). The results
      indicate that volumetric ethanol productivity is influenced by substrate
      concentration and dilution rate. The highest value 7.17 gL(-1) h(-1) is obtained
      at higher lactose concentration (150 gL(-1)) in feed medium and 0.3 h(-1)
      dilution rate. The same results have been obtained through the application of
      "LINGO" software for mathematical optimization.

PMID- 11518394
TI  - Optimization of alpha-galactosidase production in Streptomyces erythrus.
AB  - Physiological studies on Streptomyces erythrus NRRL ISP 5517 grown on fourteen
      different media have revealed that the enzyme was formed and released in the
      medium with different levels depending upon the type of the medium and the carbon
      source used. The results indicate that S. erythrus produced the highest level of
      extracellular and endocellular enzyme when grown in modified Czapek-Dox's medium
      (containing 2% D-galactose as the only carbon source). The highest levels of
      enzyme formation was obtained upon using D-galactose (9.94 Units/ml and 2.92
      Units/ml), raffinose (8.87 Units/ml and 2.69 Units/ml) or melibiose (8.14
      Units/ml and 2.52 Units/ml) at a final concentration of 2% as inducers for extra-
      and endocellular enzyme, respectively. With respect to nitrogen sources tested,
      sodium nitrate produced the highest level of alpha-galactosidase in both
      fractions optimally at 2.0 g/l. Studies revealed that the extracellular enzyme
      levels were produced optimally at initial pH in culture of 7.0 and air:medium
      ratio in flasks corresponding to 1:5 and after 5 days of incubation at 30 degrees
      C. On testing the effect of the addition of eight leguminous seeds powders (at a
      final concentration of 2%), it was found that soybean powder gave the highest
      induction effect. The addition of sodium nitrate at a concentration of 2 g/l to
      Dox's soybean medium, the adjustment of initial pH value of the medium to 7.0 and
      the air:medium ratio in flasks to 1:5 for an incubation period of 4 days produced
      the highest level of extracellular alpha-galactosidase.

PMID- 11518395
TI  - Utilization of different carbon sources by bacteria isolated from the roots of
      pine seedlings (Pinus silvestris L.) inoculated with root-free, rhizosphere and
      mycorrhizosphere soil.
AB  - Studies were carried out on the utilization of different sugars (glucose,
      fructose, arabinose, xylose, sucrose) and organic acids (acetic, citric, fumaric,
      propionic, succinic) by fast and slow growing bacteria isolated from the roots of
      pine seedlings (P. silvestris L.) inoculated with root-free, rhizosphere and
      mycorrhizosphere soil from nursery and mature pine forest. Sucrose among sugars
      and propionic acid among organic acids were the less frequently utilized
      compounds. Sugars were better carbon sources than organic acids. Proportion of
      isolates utilizing respective sugars or organic acids was, in general,
      significantly higher among fast growing bacteria as compared with slow growing
      ones. No significant differences in number of strains assimilating the appropiate
      sugars depending on their original habitat or kind of soil were observed. Such
      differences were noted for utilization of some organic acids. 3-factor ANOVA
      confirmed that the growth speed of bacteria at the moment of their isolation had
      the strongest effect on utilization of the compounds studied.

PMID- 11518396
TI  - Sequence analysis and structure prediction of aminoglycoside-resistance 16S
      rRNA:m7G methyltransferases.
AB  - Methylation of G1405 within bacterial 16S ribosomal RNA results in high-level
      resistance to specific combinations of aminoglycoside antibiotics. Only a few
      closely related methyltransferases (MTases), which carry out the respective
      modification (here dubbed "Agr", for aminoglycoside resistance), are known. It is
      not clear, whether they are related to "typical" S-adenosylmethionine (AdoMet)
      dependent MTases or not. Demydchuk et al., 1998 proposed that the cofactor
      binding region is localized at the C-terminus of Agr MTases, which implies an
      interesting case of sequence permutation. Since the Agr MTases lack significant
      sequence similarity to other proteins, we tested that hypothesis using more
      sensitive sequence/structure threading approach. Structure prediction confirmed
      the presence of a putative AdoMet-binding site in these proteins, albeit at a
      distinct location, resembling that of "typical", non-permuted MTases.
      Additionally, a small alpha-helical domain dissimilar to other proteins in the
      database was identified in the N-terminal region of Agr MTases. Comparison of a
      three-dimensional model of the Agr family member with a recently solved structure
      of reovirus mRNA capping MTase suggests that the mechanism of guanine-N7
      methylation in rRNA and mRNA may be different.

PMID- 11518397
TI  - Distribution of tannic acid degrading microorganisms in the soil and comparative
      study of tannase from two fungal strains.
AB  - A quantitative survey on microbial population including tannase producing
      organisms have been made from different soil samples. Most of the samples harbour
      negligible number of tannase producers in comparison to total microbial flora.
      Among the tannase producers, fungal members are more frequent than bacteria.
      Tannase production and tannic acid degradation have been studied in two newly
      isolated potent fungal strains. Both the strains produce maximum tannase at their
      stationary phases of growth. Enzymes produced by both the strains remain active
      within pH 3.5-6.0 and temperature 30-60 degrees C.

PMID- 11518398
TI  - How things have changed.

PMID- 11518399
TI  - Radiologic case study. Bilateral slipped capital femoral epiphysis, acute on the
      left and preslip on the right.

PMID- 11518400
TI  - Extramedullary instrumentation for TKA: a safe bet.

PMID- 11518401
TI  - Intramedullary instrumentation: safer and more accurate than extramedullary
      instrumentation.

PMID- 11518402
TI  - A simple technique for transpatellar fixation of quadriceps tendon rupture.

PMID- 11518403
TI  - The Harris-Galante Porous acetabular component at intermediate follow-up.
AB  - Outcome of the acetabular component in 90 consecutive primary noncemented total
      hip arthroplasties (THAs) was prospectively studied. The acetabular cup consisted
      of a hemispherical titanium alloy shell with a titanium fiber-mesh porous coating
      and a modular polyethylene liner (Harris-Galante Porous-1, Zimmer, Warsaw, Ind).
      The cup was implanted using line-to-line reaming with adjunctive dome screw
      fixation. The femoral component consisted of a titanium alloy stem with titanium
      fiber-mesh porous coating and a 28-mm cobalt-chrome modular head. Mean patient
      age was 53 years (range: 27-75 years); male:female ratio was 48:42; and mean
      follow-up was 6 years (range: 4.5-8 years). One acetabular component was revised
      for aseptic loosening. Of 81 unrevised hips available for follow-up, mean Harris
      hip score was 57 preoperatively and 96 at final follow-up (72% excellent, 15%
      good, 1 3% fair, and none poor). Of 61 unrevised hips with adequate radiographic
      follow-up, radiographic failure (complete periprosthetic radiolucency) was
      evident in 3 (4.9%) and periacetabular osteolysis in none. Radiographic failure
      did not correlate with poor clinical outcome. Linear polyethylene wear rate
      (mean: 0.13 mm/year) did not correlate with age, gender, weight, outcome, or cup
      abduction angle, but did correlate with the presence of femoral periprosthetic
      osteolysis (0.18 mm/year with femoral osteolysis versus 0.11 mm/year without; P=
      .01). This series of porous-coated hemispherical cups demonstrated excellent
      intermediate-term clinical and radiographic outcome, comparable with similarly
      favorable results reported by the prosthesis designers. A potentially adverse
      effect of polyethylene wear on the longevity of a THA was supported by a positive
      correlation between polyethylene wear rate and femoral osteolysis.

PMID- 11518404
TI  - Exchange nailing for failure of initially rodded tibial shaft fractures.
AB  - This retrospective study evaluated 32 patients who underwent exchange nailing for
      initially rodded nonunited tibial shaft fractures during a 5-year period. High
      energy trauma accounted for 22 fractures; 19 fractures were open. An unreamed
      nail was initially used to stabilize all but 2 fractures. Implant failure
      occurred in 31% of fractures, mostly in distal-third fractures, with a failure
      rate of 34%. Average time from injury to exchange nailing was 36 weeks (range: 6
      148 weeks) and consisted of closed reamed nailing and fibulectomy in 27 cases.
      Healing occurred an average of 20 weeks (range: 6-47 weeks) after postexchange
      nailing in 27 (84%) fractures. Four (12.5%) fractures healed after additional
      procedures. There was 1 persistent nonunion. Factors leading to delay in union
      time included comminution, healed fibula, and proximal location. Multiple
      regression analysis using survival data at P<.05 showed a significant correlation
      between fracture configuration and fixation method (locked, dynamic, and
      unlocked) on time to union. Exchange nailing with closed reaming and fibulectomy
      is a viable option for treating failures of primarily nailed tibial fractures.
      Increased stability and stimulation of arrested bone healing may account for the
      good outcome. The advantages of repeat reamed nailings should be weighed against
      the possible adverse effect of reaming on bone vascularity.

PMID- 11518405
TI  - The possible role of locally produced cytokines in the pathogenesis of
      peritrochanteric fractures in the elderly.
AB  - Sixteen patients with intertrochanteric femoral fractures were studied for
      possible involvement of the cytokines interleukin-6 (IL-6), interleukin-1 beta
      (IL-1beta), tumor necrosis factor-alpha, and the disease activity factors C
      reactive protein and alpha1-antitrypsin as local bone-resorbing agents. Cytokine
      and disease activity factor levels were measured in gluteus medius muscle and
      serum samples and were compared to sera obtained from age- and sex-matched
      healthy controls. Interleukin-6 and IL-1beta levels were significantly higher
      (P=.0024 and P=.036, respectively) in the muscle samples from the fractured side
      than in the samples from the contralateral unaffected side. Levels of IL-6 and IL
      1beta also were significantly higher in patients' sera than in the sera of
      healthy controls. These results support a new hypothesis that may contribute to
      the pathogenesis of fractures in the elderly: unilaterally locally over-produced
      IL-6 and IL-1beta may lead to local bone resorption in the intertrochanteric
      region, which subsequently weakens the femoral bone and increases the risk of
      unilateral peritrochanteric fractures.

PMID- 11518406
TI  - Magnetic resonance imaging of periarticular titanium screws.
AB  - Magnetic resonance imaging (MRI) may be the most sensitive modality for detecting
      post-traumatic degeneration of articular cartilage. Magnetic resonance imaging
      must accurately depict articular cartilage in the presence of periarticular
      fracture stabilization devices to be effective for postoperative imaging of
      articular fractures. This study examines how close titanium screws can be
      inserted to tibial articular surfaces and still allow accurate MRI of the
      overlying articular cartilage. Cannulated titanium screws were inserted at
      varying distances from subchondral bone in the proximal and distal tibiae of
      embalmed human cadaveric legs, which were then imaged using a standard nonfat
      saturated fast low angle shot two-dimensional sequence (FLASH 2D). The distance
      from the center of the screw to the subchondral bone and the thickness of the
      articular cartilage directly overlying the screw was then determined by direct
      measurement and by measurement on the scanned images. To allow FLASH 2D MRI of
      the articular cartilage, 7.3-mm screws had to be at least 13 mm from the
      subchondral bone, and 4.5-mm screws had to be at least 12 mm from the subchondral
      bone. For MRI to be effective for the postoperative imaging of the articular
      surface following severe articular fractures of the tibia, titanium fracture
      hardware must be farther away from the articular surface than these minimum
      distances. Alternate materials for stabilizing articular fractures are available
      and may allow clearer and more accurate imaging of the articular cartilage when
      inserted close to the articular surface.

PMID- 11518407
TI  - Evaluation of suspected stress fractures.
AB  - Stress fractures can occur if normal bone is exposed to repeated abnormal stress
      (fatigue fractures) or if normal stress is placed on bones with compromised
      elastic resistance (insufficiency fractures). This article describes two patients
      without a history of excessive stressful activity or apparent metabolic bone
      disease who developed bilateral distal tibial stress fractures. Different
      etiologies, clinical presentation, differential diagnosis, and diagnostic imaging
      modalities of stress fractures are discussed.

PMID- 11518408
TI  - Joint synovial osteochondromatosis following high-voltage electrical injury to
      the extremities.

PMID- 11518409
TI  - Role of FGF9 and FGF receptor 3 in osteochondroma formation.
AB  - Osteochondromas are chondro-osseous protuberances that occur in metaphyses of
      long bones. The cartilaginous cap is assumed to be responsible for the growth of
      the lesions during childhood and adolescence, but mitotic figures are rarely seen
      in the cap. Therefore, another cell population, probably mesenchymal cells, is
      responsible for proliferation and growth. Residual mesenchymal cells capable of
      rapid proliferation are difficult to detect due to lack of specific histologic
      features. Two specific markers for mesenchymal cells, FGF receptor 3 (FGFR3) and
      collagen type IIa, have been described. Osteochondroma mesenchymal cells are
      found in the soft tissues overlying the cartilage cap. The surrounding areas of
      typical cartilage are negative for both mesenchymal cell associated antigens. The
      soft tissues overlying the cartilage do not have cartilaginous features. The
      undifferentiated cells overlying the exostosis yield in culture a rapidly
      proliferating homogenous population of fibroblast-like cells. Expression at the
      mRNA level of FGF9, FGFR3, and collagen type IIa is found in these cells, but not
      in skin fibroblasts from afflicted or healthy individuals. Exogenous
      administration of TGFbeta1 to cultures of hereditary multiple exostosis
      eliminates FGF9 expression. These results indicate fibrous regions contain the
      mesenchymal cells responsible for osteochondroma growth.

PMID- 11518410
TI  - Chylothorax after video-assisted thoracoscopic release for rigid scoliosis.

PMID- 11518411
TI  - Spontaneous regression of a hemophilic pseudotumor.

PMID- 11518412
TI  - Thoracic outlet syndrome secondary to an anomalous subclavius muscle.

PMID- 11518413
TI  - Angiosarcoma of bone following intramedullary nail fixation.

PMID- 11518414
TI  - Rotator interval lesions of the shoulder joint.

PMID- 11518415
TI  - What is your diagnosis? Rupture of the insertion of the biceps brachii from the
      radial tuberosity.

PMID- 11518417
TI  - 'Battered pets': Munchausen syndrome by proxy (factitious illness by proxy).
AB  - Nine cases of suspected Munchausen syndrome by proxy (MSBP), involving pets as
      proxies, were identified among 448 cases of non-accidental injury to small
      animals. These cases, recorded by a random sample of small animal practitioners
      in the UK, demonstrated several combinations of features, including attention
      seeking behaviour by the owner, real and apparently factitious clinical signs,
      deliberate injury, markedly abnormal biochemical profiles, serial incidents,
      interference with surgical sites, recovery after separation from the owner, and
      'veterinarian-shopping' by the owner. All of these features are consistent with
      those identified in the well documented MSBP in which children are the victims.
      Furthermore, one of the cases involved serial attempts at poisoning other animals
      and a child.

PMID- 11518416
TI  - Prognostic variables in canine multicentric lymphosarcoma.
AB  - This paper presents the results of a prospective study to investigate the
      prognostic value of clinical staging, histological grading, immunophenotype,
      mitotic count and average numbers of argyrophilic nucleolar organiser region
      counts in dogs with multicentric lymphosarcoma treated with a standard
      chemotherapy protocol comprising vincristine, cyclophosphamide and prednisolone.
      Forty-nine dogs were treated according to the study protocol. Univariate and
      multivariate analysis with regression modelling was used to evaluate the
      prognostic importance of patient and tumour variables upon tumour response and
      relapse-free survival. Thirty-seven dogs (76 per cent) achieved a complete
      remission, seven (14 per cent) a partial remission and five (10 per cent) failed
      to respond to treatment. None of the variables examined had a statistically
      significant effect upon tumour response. Tumour immunophenotype was the only
      parameter found to have a significant influence on patient survival, the hazard
      ratio for T-cell versus B-cell immunophenotype was 3.99 with 95 per cent
      confidence interval from 1.399 to 11.372, P = 0.035.

PMID- 11518418
TI  - Rupture of the cranial cruciate ligament associated with deformity of the
      proximal tibia in five dogs.
AB  - Excessive mechanical stress due to caudal sloping of the tibial plateau may
      result in early breakdown of the cranial cruciate ligament (CrCL). Five dogs with
      CrCL rupture associated with caudal sloping of the proximal tibial plateau are
      described. All were small dogs, of between three and six years of age, with a
      mean bodyweight of 9.3 kg, which had acute hindlimb lameness. Radiographic
      examination revealed cranial displacement of the tibia, with a tibial angle
      varying from 58 to 60 degrees. All cases were treated with a lateral
      fabellotibial suture and cranial cuneiform osteotomy of the proximal tibia. All
      dogs were using the operated limb three days after surgery, with normal gait re
      established after a mean period of 10 days. Excessive tibial plateau sloping is
      not a frequent cause of hindlimb lameness in small animals, although it is
      important to consider it as a predisposing factor for rupture of the CrCL.

PMID- 11518419
TI  - Incomplete humeral condylar fractures in the dog.
AB  - The details of eight dogs (11 elbows) referred to the authors with lameness
      relating to elbow pain associated with incomplete fracture of the humeral condyle
      were reviewed. In all cases, a diagnosis was reached by radiographic examination,
      with the pathognomonic feature being a radiolucent line, in the sagittal plane,
      through the condyle. Treatment involved placement of a transcondylar bone screw
      with or without bone tunnels being created parallel to this implant. Six dogs
      (nine elbows) made a complete recovery without subsequent complications.

PMID- 11518420
TI  - Vascular hamartoma within the flexor muscles of the left carpus in a dog.
AB  - A three-year-old male bearded collie was presented with a history of left
      thoracic limb lameness and a fluctuant non-painful swelling within the flexor
      tendons of the left carpus. Investigations included ultrasonography, laboratory
      analysis of fluid aspirated from the lesion and positive contrast radiography.
      Treatment involved surgical resection of the lesion from the local flexor muscles
      of the carpus. Histologically, the resected tissue was considered to represent a
      vascular hamartoma associated with the pronator quadratus muscle.

PMID- 11518421
TI  - Treatment of partial seizures and seizure-like activity with felbamate in six
      dogs.
AB  - Six dogs with partial seizures or partial seizure-like activity were treated with
      the antiepileptic drug felbamate between 1993 and 1998. All dogs had a history
      and results of diagnostic testing suggestive of either primary (idiopathic) or
      occult secondary epilepsy. Dogs ranged between four months and eight years of age
      at the onset of seizure activity. The median time period between onset of the
      first seizure and the start of felbamate therapy was 3.8 months (range 0.75 to 36
      months). Median duration of therapy was nine months (range two to 22 months). All
      dogs experienced a reduction in seizure frequency after felbamate administration.
      Median total number of seizures post-treatment was two (range 0 to 9). Two dogs
      had an immediate and prolonged cessation of seizure activity. Steady-state trough
      serum felbamate concentrations measured at two weeks, and one, 12 and 22 months
      after the commencement of therapy in four dogs ranged between 13 and 55 mg/litre
      (median 35 mg/litre). Reversible haematological adverse effects were detected in
      two dogs, with one dog developing concurrent keratoconjunctivitis sicca. These
      results suggest that felbamate can be an effective antiepileptic drug without
      life-threatening complications when used as monotherapy for partial seizures in
      the dog.

PMID- 11518422
TI  - Diagnosis of cerebellar cortical degeneration in a Scottish terrier using
      magnetic resonance imaging.
AB  - Primary cerebellar cortical degeneration (CCD), also termed abiotrophy, is the
      spontaneous premature degeneration of fully differentiated neurological tissue.
      Cerebellar hypoplasia shares many morphological features with primary CCD, both
      conditions being characterised by decreased cerebellar size, with reduced numbers
      of Purkinje and granular cells. CCD has been identified in many canine breeds.
      This is the first report of the syndrome in a Scottish terrier. The patient
      presented with mild, gradually progressive ataxia. Survey radiographs of the
      cervical spine and cerebrospinal fluid (CSF) analysis were normal. CSF distemper
      and Toxoplasma titres were negative. A diagnosis of cerebellar atrophy was made
      based on magnetic resonance imaging. The progressive clinical signs suggested
      cerebellar degeneration rather than hypoplasia. On necropsy, the cerebellum
      showed macroscopic and microscopic changes consistent with primary CCD.

PMID- 11518424
TI  - Experiences of a small animal practitioner turned TVI.

PMID- 11518423
TI  - Identification of focal adenomyosis as a uterine lesion in two dogs.
AB  - A focal uterine adenomyosis is described in two bitches. In both cases, the
      uterus showed knobbly enlargements of 4 to 8 cm in diameter, which resulted in
      distinct clinical symptoms. Other pathological changes of the uterus were not
      present. One bitch was presented because of a history of vaginal discharge of
      several months' duration. Radiographs, as well as ultrasonography, revealed a
      soft tissue lesion at the cervix. The other bitch showed a marked reduction in
      its general condition and a sudden onset of a tense abdomen. Radiologically, a
      lesion of soft tissue opacity was observed in the mid-abdomen and was seen to
      originate from the left uterine horn during exploratory laparotomy. A torsion of
      the lesion was present, which explained the clinical signs in this second case.

PMID- 11518425
TI  - Future vaccine schedules may be more tailored to pet lifestyles.

PMID- 11518426
TI  - Seeking global standardisation on liver disease.

PMID- 11518427
TI  - Salmonella Typhimurium definitive type 104. A multi-resistant Salmonella.

PMID- 11518428
TI  - Impedance measurements to study the antimicrobial activity of essential oils from
      Lamiaceae and Compositae.
AB  - A wide range of essential oils from sage, mint, hyssop, camomile and oregano were
      tested for their inhibitory effects against nine strains of gram-negative
      bacteria and six strains of gram-positive bacteria. Three principles were used in
      describing the antimicrobial effects of the essential oils: the overall
      antimicrobial activity determined by use of an impedometric method, the
      bactericidal effect determined as colony forming units after exposure to the
      essential oils, and the number of apparent dead cells determined after further
      enrichment. The data obtained indicate that while the essential oils of sage,
      mint, hyssop and camomile had generally a bacteriostatic activity, the essential
      oil from oregano appeared to be bactericidal at concentrations above 400 ppm,
      probably because of high contents in phenolic compounds. For the other essential
      oils, the chemical analysis was unable to explain the antimicrobial effect. The
      bacteriostatic activity was more marked against gram-positive bacteria; in
      contrast, the bactericidal activity was greatest against gram-negative bacteria.
      The most sensitive strain was Escherichia coli O157:H7 and, of the gram-positive
      species even at the lowest oil concentrations, Listeria innocua was the most
      sensitive. The data obtained from the study of the bactericidal effect of oregano
      essential oil indicated that the major part of the species was irreversibly
      inactivated, i.e. they could not be revived by enrichment.

PMID- 11518429
TI  - Contribution of starter culture to the sensory characteristics of fermented
      Almagro eggplants.
AB  - Trial fermentations were performed using three experimental starter cultures with
      a view to selecting the most appropriate starter for use in the manufacture of
      Almagro eggplants. The lactic acid bacterial strains used in the starters had
      previously been isolated from spontaneous fermentations. The combined action of
      the obligate heterofermentative species Lactobacillus brevis and the facultative
      heterofermentative species L. plantarum yielded Almagro eggplants with sensory
      properties preferred by panelists. Conversely, another obligate
      heterofermentative species, namely, L. fermentum, present in certain starter
      formulations tested, appeared to encounter difficulty growing during fermentation
      and exerted little influence on the sensory characteristics of the eggplants
      produced.

PMID- 11518430
TI  - In vitro adherence properties of Lactobacillus rhamnosus DR20 and Bifidobacterium
      lactis DR10 strains and their antagonistic activity against an enterotoxigenic
      Escherichia coli.
AB  - Adhesion and colonisation properties of three probiotic strains namely,
      Lactobacillus rhamnosus DR20, L. acidophilus HN017, and Bifidobacterium lactis
      DR10, were determined in vitro using the differentiated human intestinal cell
      lines including HT-29, Caco-2, and HT29-MTX, and compared with properties of L.
      acidophilus LA-1 and L. rhamnosus GG (two commercial probiotic strains). Two
      independent methods were employed to quantitate the "adhesiveness" of each
      strain. In the first method, the bacteria adhered to human cells were detected by
      Gram staining and counted in different fields under a microscope. Bacteria were
      also radio-labelled and extent of adhesion determined by scintillation counting.
      All three strains showed strong adhesion with the human intestinal cell lines in
      vitro. Adhesion indices of the three strains to two cell lines, i.e. HT-29, and
      Caco-2 varied between 99 +/- 17 and 219 +/- 36. With mucus-secreting cell-line
      HT29-MTX, the adhesion indices of all the strains were 2-3 times higher. The
      adhesion indices of L. acidophilus LA-1 and L. rhamnosus GG were comparable to
      the other three probiotic strains. We also investigated the inhibitory effect of
      adhering strains against the intestinal cell monolayer colonization by a known
      enterotoxigenic strain of Escherichia coli (strain O157:H7). Pre-treatment of E.
      coli O157:H7 with 2.5-fold concentrated cell-free culture supernatants from L.
      acidophilus HN017, L. rhamnosus DR20 and B. lactis DR10 reduced the culturable E.
      coli numbers on TSB plates and also reduced the invasiveness and cell association
      characteristics of this toxic strain. The inhibitory molecules secreted into the
      spent media by these strains were partially affected by treatments with lactate
      dehydrogenase, trypsin and proteinase K suggesting that overall inhibition may be
      due to a synergistic action of lactic acid and proteinaceous substances.

PMID- 11518431
TI  - Effect of different cultivation conditions on Lactobacillus manihotivorans
      OND32T, an amylolytic lactobacillus isolated from sour starch cassava
      fermentation.
AB  - Study of the cassava sour starch fermentation has led to the isolation of a new
      homofermentative amylolytic lactic acid bacterium, Lactobacillus manihotivorans
      OND32T, whose nutritional requirements have been investigated in this work. The
      main effect of deleting one of the substrate components of the MRS-starch medium
      was to reduce the amylase production. When starch fermentation with nitrogen as a
      gas phase was compared to fermentation under aerobic conditions, both growth and
      amylase production were reduced whereas lactic acid formation was not affected.
      Addition of carbon dioxide (> or = 20% v/v) to the nitrogen gas phase restored
      growth and amylase production. The amylase production was high with starch,
      maltose or cellobiose contrary to glucose, fructose and sucrose. During mixed
      fermentation of glucose and maltose, a diauxic growth was observed. The maltose
      consumption and the amylase production started after the glucose depletion. The
      presence of maltose altered the carbon assimilation from glucose, whereas the
      energetic pathway was not affected. It is concluded that the elimination of
      soluble sugars by the wet extraction of starch during the processing of cassava,
      together with the expected in situ CO2 production, are conditions favouring the
      growth and the amylase synthesis. However, these are likely to be limited by the
      low nitrogen content in cassava.

PMID- 11518433
TI  - Involvement of osmotic cell shrinkage on the proton extrusion rate in
      Saccharomyces cerevisiae.
AB  - Saccharomyces cerevisiae has been subjected to hyperosmotic shocks by using
      permeating (sorbitol, xylitol, glycerol, NaCl) and nonpermeating (PEG 600)
      solutes. The proton extrusion rate decreased as the osmotic pressure increased,
      whichever solute was used. However, the total inhibition of the cellular H+
      extrusion depended on the solute used. A total inhibition was observed at about
      20 MPa with glycerol, xylitol and sorbitol. With PEG 600, a total inhibition of
      extracellular acidification was obtained at 8.5 MPa. NaCl, with an extracellular
      pressure of 37.8 MPa (near saturation), did not completely inhibit the
      extracellular acidification. These results showed that the total inhibition of
      proton extrusion, involving probably the membrane H+-ATPase. was not correlated
      to the hydric state of the external medium but was strictly linked to the degree
      of permeation of solutes across the plasma membrane. The extracellular
      acidification was totally inhibited by a critical final cell volume reached after
      the osmotic shrinkage, whichever solute was used. This critical final cell volume
      represented 50% of the initial cell volume. This result suggests that the final
      cell volume reached after an osmotic stress represents a key thermodynamic
      parameter for cell osmoregulation in which H+-ATPase would be implicated.

PMID- 11518432
TI  - Modelling the effects of (green) antifungals, droplet size distribution and
      temperature on mould outgrowth in water-in-oil emulsions.
AB  - Prevention of fungal spoilage is a key microbiological issue for the shelf life
      of fat spreads. Our aim was to assess and model the scope of (natural)
      antimicrobials for extending shelf life of spreads (water-in-oil emulsions).
      Production conditions were established to make 60% model fat spreads with
      reproducible droplet size distributions. The mould vulnerabilities ranged from 1
      to 20 weeks. The system allowed feasibility testing of lytic enzymes (Novozym
      234) and LMW compounds against Penicillium roqueforti, a key-spoilage mould. The
      action of Novozym 234, carvacrol, undecanol and dihydrocarveol was benchmarked
      against sorbate and preservative-free controls under ambient and chilled
      conditions. Novozym 234 was ineffective to prevent outgrowth of P. roqueforti.
      Carvacrol, undecanol and dihydrocarveol had limited effects on shelf-life
      extension compared to sorbate. Fungal growth boundaries of (un-)preserved spreads
      were modelled. The emulsion droplet size distribution (DSD) was first captured in
      a mechanistic parameter DSD-I (I = Influence). DSD-I was a move away from the
      mean droplet diameter D3,3 as sole quantitative droplet-size distribution
      parameter for mould susceptibility of emulsions. DSD-I is a combination of
      available water droplets and surface area to initiate and sustain fungal
      outgrowth. Followup experiments showed that modelling D3,3 and distribution width
      (e(sigma)) instead of DSD-I gave better results for emulsions with high e(sigma).
      Empirical predictive models were subsequently developed for the effects of D3,3,
      e(sigma) and undissociated sorbic acid (HSO) on the shelf life of emulsions.

PMID- 11518434
TI  - Microbiological and biochemical studies on Gergoush fermentation.
AB  - According to the results obtained, three steps in Gergoush fermentation were
      identified. Step one is the primary starter preparation and comprises a 12-15 h
      propagation of the natural thermotolerant bacterial flora of the legume
      ingredient of Gergoush using the legume and boiled milk as a propagation medium.
      This primary starter is then used in step two to inoculate a wheat flour dough to
      produce the adapted starter in a 1-2-h fermentation time. The adapted starter is
      finally used in step three to raise the main Gergoush dough. In all of the three
      steps of Gergoush fermentation, three genera of bacteria dominated. They were
      tentatively identified as lactic acid bacteria, Bacillus spp. and Clostridium
      spp. Their counts reached a maximum in the primary starter stage of 2.2 x 10(7),
      2.8 x 10(8) and 7.3 x 10(7) CFU/g, respectively. These bacteria produced lactic,
      acetic and butyric acids. The concentrations of the acids were maximum in the
      primary starter and reached values of 0.6%, 0.4% and 0.5%, respectively, and the
      pH decreased from 6.1 to 4.1. Baked Gergoush has a pH of about 5 and contains
      about 59% starch, 16% protein, 18% fat, 6.5% water and 0.5% ash.

PMID- 11518435
TI  - Medically unexplained disability--a misnomer, and an opportunity for
      rehabilitation.

PMID- 11518436
TI  - Effectiveness of dynamic cognitive intervention in rehabilitation of clients with
      schizophrenia.
AB  - OBJECTIVE: To examine the efficacy of dynamic cognitive treatment in
      rehabilitation of schizophrenic clients. SUBJECTS: Fifty-eight schizophrenic
      clients that were matched equally into two groups: a study group (n = 29)
      (treated by Instrumental Enrichment) and a control group (treated with
      traditional occupational therapy methods). SETTING: The subjects were treated in
      a day rehabilitation centre in the community. STUDY DESIGN: The programme lasted
      one year, the same schedule was provided for both groups. Subjects were randomly
      assigned and assessed before and after intervention with the same battery and at
      a follow-up six months later, work and residence status were evaluated. MAIN
      OUTCOME MEASURES: Instruments included: (1) memory and thought processes,
      measured by a battery of structured tests from the Learning Potential Assessment
      Device (LPAD), Raven Progressive Matrices and General Aptitude Test Battery
      (GATB); (2) functional outcomes, instrumental activities of daily living (IADL),
      measured by a questionnaire; work and residence status; (3) self-concept measured
      with Fitts questionnaire. RESULTS: Results showed significant differences between
      the groups on almost all the cognitive tests (MANOVA revealed significant
      differences between the two groups for both memory and thought process (F(2.52) =
      13.75, p < 0.001; and F(1.46) = 7.28, p < 0.001, respectively) as well as in work
      (chi2 = 14.30, p < 0.001), and residence (chi2 = 3.86, p < 0.05) status. There
      were no significant differences in IADL questionnaire or the self-concept scale.
      CONCLUSIONS: The successful outcome points to the importance of including long
      term cognitive intervention in rehabilitation of schizophrenic clients. This work
      suggests that the classic view of schizophrenia as a progressive irreversible
      decline that cannot be altered may be wrong.

PMID- 11518437
TI  - Children with asthma and physical exercise: effects of an exercise programme.
AB  - OBJECTIVE: To evaluate the effects of a physical exercise programme for children
      with asthma on an outpatient basis. DESIGN: Intervention study: a randomized
      pretest-post-test control group design. SETTING AND SUBJECTS: Forty-seven
      children with clinically diagnosed asthma participated in the intervention study,
      including 34 boys and 13 girls, from 8 to 13 years of age (mean age 10.6).
      INTERVENTIONS: The physical exercise programme consisted of regular group
      exercises and home exercises for a period of three months. It was based on a
      theoretical model describing the relationships between physical competence
      (condition), perceived physical competence, self-esteem and coping behaviour.
      MAIN OUTCOME MEASURES: Maximum incremental exercise test, endurance test, the
      Self-Perception Profile for Children (CBSK), the Asthma Coping Test (ACBT), lung
      function and exercise-induced bronchoconstriction. RESULTS: The results showed
      significant effects of the intervention programme on physical condition. There
      was a significant improvement of 15 W on the maximal workload (Wmax) (p < 0.001),
      of 7% on VO2max (oxygen uptake) (p = 0.002) and a significant decrease on heart
      rate submaximal of 6% (p = 0.001). There was also a significant improvement of
      50% in running time measured with the endurance test (p = 0.021). Furthermore, a
      significant effect of the intervention was seen on coping with asthma (p =
      0.003). CONCLUSION: It was concluded that participation in the physical exercise
      programme not only enhanced physical fitness, but also improved coping behaviour
      with asthma.

PMID- 11518438
TI  - A new, comprehensive normative database of lumbar spine ranges of motion.
AB  - AIMS AND OBJECTIVES: To generate gender-specific and broadly based age-related
      indices for normative lumbar ranges of motion for all planes of movement. DESIGN:
      This was a repeated measures prospective study of spinal range of motion in a
      sample of volunteer subjects utilizing a portable modified CA6000 Spine Motion
      Analyzer (Orthopedic Systems Inc., Union City, CA, USA). SETTING: Data collection
      was carried out in a variety of community locations including fire, police and
      ambulance stations, offices and community centres. SUBJECTS: A total of 405
      asymptomatic subjects (196 female, 209 male) were recruited, aged 16-90 years,
      from sedentary, mixed and physically demanding occupations. METHODOLOGY: Indices
      of lumbar spine ranges of motion were measured in standing following a
      standardized protocol for sagittal flexion/extension, coronal lateral flexion and
      horizontal axial rotation movements. RESULTS: Male and female normative flexion
      ranges declined by approximately 40% (72-40 degrees) across the age spectrum.
      Extension declined the greatest, by approximately 76% (29-6 degrees) overall. In
      lateral flexion male and female ranges declined approximately 43% (29-15 degrees)
      in each direction (total 58-30 degrees). In axial rotation no age-related decline
      was observed and ranges of motion remained at approximately 7 degrees in each
      direction (total 14 degrees) across all the ages of the subject group.
      CONCLUSIONS: Data have been generated that provide comprehensive, gender
      specific, broadly based and age-related indices for normative lumbar ranges of
      motion in all planes of movement. These are applicable to individuals throughout
      adult life, from adolescence through to old age.

PMID- 11518439
TI  - Nurses' perceptions of physiotherapists as rehabilitation team members.
AB  - OBJECTIVE: To investigate nurses' perceptions of physiotherapists as members of
      the rehabilitation team. This study arose from the current emphasis that is
      placed on good multidisciplinary teamwork for effective rehabilitation and the
      awareness that different team members often have different perceptions of their
      respective roles within the team. DESIGN: Semi-structured interviews, the results
      of which were then subject to content analysis. SETTING AND SUBJECTS: Experienced
      rehabilitation nurses in two rehabilitation wards within a National Health
      Service Trust. RESULTS: Nurses perceived the role of physiotherapists as being
      concerned with mobility and movement, and valued the therapists' knowledge and
      skills in these areas. They felt, however, that physiotherapists had insufficient
      understanding of the demands and pressures of nursing practice and lacked
      recognition of the nurses' professional autonomy in decision-making in
      rehabilitation. Nurses viewed nursing and physiotherapy as two quite distinct and
      different roles within rehabilitation, despite some role overlap. Physiotherapy
      was perceived as specific and measurable, while nursing was perceived as
      generalized and undefined. These perceptions extended to their views on patient
      staff interactions and organizational structures. Some of the differences, such
      as organizational structures, created barriers to rehabilitation. Others, such as
      physiotherapy expertise in mobility, were valued for their contribution to
      rehabilitation. Areas were identified where the two professions can assist each
      other in professional skills. CONCLUSION: Nurses valued the role and contribution
      of physiotherapists, but identified areas in which barriers existed to effective
      interprofessional working, particularly in relation to organizational factors and
      interprofessional relationships.

PMID- 11518440
TI  - An exploration of the effects of weighted garments on balance and gait of stroke
      patients with residual disability.
AB  - OBJECTIVE: To explore the effects of weighted garments on the balance and gait of
      stroke patients. DESIGN: A pilot randomized controlled study with blinded
      measurement. SETTING: Weighted garments were worn by patients living in the
      community and measurement was made in a hospital-based gait laboratory. SUBJECTS:
      Twenty-four adults who were at least six months post stroke and were able to walk
      10 metres with or without assistance or a walking aid. INTERVENTION: The six-week
      treatment-phase subjects were given a set of weighted garments which they were
      shown how to apply and instructed to wear on their paretic side. Subjects
      randomly allocated to the six-week control phase were not given any weighted
      garments. MAIN OUTCOME MEASURES: Balance was measured with the Berg Balance
      Scale. Gait was measured using GaitMat II, an instrumented walkway. Gait
      parameters of interest were velocity and symmetry of: step length; single support
      time; double support time; and support base width. Measures were made at baseline
      before randomization (baseline) and at the end of the six weeks of intervention
      (outcome). RESULTS: No statistically significant differences were found between
      the treatment and control groups at outcome for balance (Mann-Whitney U-test; p =
      0.74), gait velocity (p = 0.68) or symmetry of gait parameters (p = 0.33 to p =
      0.75). CONCLUSIONS: We found no evidence to support the clinical use of these
      weighted garments for stroke survivors.

PMID- 11518441
TI  - Comparison of the content of two physiotherapy approaches for stroke.
AB  - OBJECTIVE: To identify similarities and differences between a Bobath-based (BB)
      and a movement science-based (MSB) approach. DESIGN: Direct observation by a
      trained observer was used to record behaviours during treatments. SETTING: An
      acute stroke ward. SUBJECTS: Twenty-two stroke patients. INTERVENTIONS:
      Behaviours were recorded during 12 treatment sessions by three therapists, for
      each treatment approach. Physical and communication behaviours were recorded in
      pre-defined categories. The equipment used was recorded and a semi-structured
      interview conducted with the therapist after treatment to identify follow-up
      actions by the therapist. MAIN OUTCOME MEASURES: Frequency of occurrence of each
      category was compared between the approaches. RESULTS: Treatment in the BB group
      contained more social conversation (p = 0.004), and more use of physiotherapy
      equipment (p = 0.02) and a physiotherapy assistant (p = 0.01). In the MSB group
      there was more detailed feedback given to the patient (p = 0.002) more use of
      everyday objects in training (p = 0.001), therapists more frequently listed
      specific components as the patient's main problems (p = 0.003) and relatives were
      involved more in positioning to stretch muscles (p = 0.03). Training walking was
      given more emphasis in the BB group and training of sit-to-stand in the MSB
      group. CONCLUSIONS: The study indicates that there are differences in content
      between the Bobath-based and movement science-based approaches to treatment.

PMID- 11518442
TI  - Walking speed over 10 metres overestimates locomotor capacity after stroke.
AB  - OBJECTIVE: To examine 10-m comfortable walking speed and 6-minute distance in
      healthy individuals and individuals after stroke and to assess the level of
      disability associated with poor walking endurance after stroke. DESIGN:
      Descriptive study in which comfortable walking speed over 10 m and distance
      covered in 6 minutes (6-minute walk test) were compared between healthy subjects
      and subjects after stroke. SUBJECTS: Twelve healthy subjects and 14 subjects
      after stroke. MAIN OUTCOME MEASURES: Walking speed and 6-minute distances were
      compared between groups. In addition, for each group, actual distance walked in 6
      minutes was compared with the distance predicted by the 10-m walking speed test
      and the distance predicted by normative reference equations. RESULTS: Subjects
      after stroke had significant reductions in 10-m speed and 6-minute distance
      compared with healthy subjects (p < 0.05). Subjects after stroke were not able to
      maintain their comfortable walking speed for 6 minutes, whereas healthy subjects
      walked in excess of their comfortable speed for 6 minutes. The average distance
      walked in 6 minutes by individuals after stroke was only 49.8+/-23.9% of the
      distance predicted for healthy individuals with similar physical characteristics.
      CONCLUSION: In our subjects after stroke, walking speed over a short distance
      overestimated the distance walked in 6 minutes. Both walking speed and endurance
      need to be measured and trained during rehabilitation.

PMID- 11518443
TI  - Factors influencing rate of Barthel Index change in hospital following stroke.
AB  - BACKGROUND AND PURPOSE: Randomized controlled trials of specific interventions in
      stroke rehabilitation are few. In using this study design to compare different
      rehabilitation interventions or different intensity of those interventions,
      measuring disability status at a fixed time point is one outcome option. In order
      for this approach to be valid, factors that might independently affect the speed
      of disability change have to be matched at baseline. We sought to investigate the
      impact of different factors on rate of disability change following stroke.
      METHODS: A prospective hospital-based study of consecutive patients admitted to
      each of three general hospitals in Wellington, New Zealand with acute stroke.
      Patients were assessed using the Barthel Index (BI, scored 0-20) within a few
      days of stroke and fortnightly until hospital discharge. Strokes were classified
      using the Oxfordshire Community Stroke Project classification. MAIN OUTCOME
      MEASURE: Barthel Index rate of change (BRC) computed from the difference between
      the first and last hospital BI scores divided by the time in weeks between these
      assessments. RESULTS: Of 104 subjects with two or more disability assessments in
      hospital, BRC was a mean 1.26 units per week (95% confidence interval (CI) 0.97,
      1.56). The only factors significantly associated with BRC on univariate analysis
      were stroke type, pre-stroke Modified Rankin Scale (MRS) and pre-stroke London
      Handicap Score. In a general linear model analysis of covariance, stroke type (p
      = 0.015) and pre-stroke MRS (p < 0.001) remained significant. The mean BRC for
      lacunar infarcts (1.76 units per week, 95% CI 1.22, 2.30) was over three times
      that of total anterior circulation infarcts (0.48 units per week, 95% CI 0.20,
      0.76). CONCLUSIONS: Future randomized controlled trials of rehabilitation
      interventions for stroke in hospitalized patients need to allow for pre-stroke
      level of dependence and stroke type in the study design, either excluding
      particular patients or ensuring even randomization of these key variables if
      speed of disability change is to be a valid outcome variable.

PMID- 11518444
TI  - Stroke: an exploration of the experience of informal caregiving.
AB  - OBJECTIVE: To explore the experience of caregiving in informal carers of stroke
      patients. DESIGN: The research approach was qualitative. Data were collected one
      year after the stroke occurred using a semi-structured interview. The audio-taped
      interviews were transcribed and following this process were analysed thematically
      using constant comparative procedures. SETTING: West of Scotland. SUBJECTS:
      Twenty-two informal carers of stroke patients. RESULTS: The results are presented
      under the headings: Preparation for discharge/feelings about discharge; The early
      weeks/months at home; A year of caring; and The future. The main themes
      identified within these broad areas were as follows: physical preparation;
      emotional support; the supply of information and advice; and the provision of
      appropriate services (both social and health service provision). CONCLUSIONS: The
      data gathered in this small-scale study suggest that the physical and emotional
      toll associated with caregiving was great. Unfortunately, the help and support
      provided by the health and social services was often inadequate, inappropriate
      and poorly tailored to their individual needs. There was little evidence of a
      seamless flow of care between the secondary and primary care settings.

PMID- 11518445
TI  - A pilot study of attention deficits, balance control and falls in the subacute
      stage following stroke.
AB  - OBJECTIVES: To (1) identify and monitor changes in deficits of attention and
      balance in the subacute stage following stroke, (2) investigate fall events, (3)
      explore relationships between deficits of attention, balance and falling post
      stroke. DESIGN: A prospective observational study. SETTING: Hospitalized patients
      with stroke were recruited from a rehabilitation ward. SUBJECTS: Fourteen
      subjects were recruited, 13 subjects (age 21-80 years) completed all assessments.
      Ten had right and three had left hemispheric lesions. Eight subjects were male.
      MAIN OUTCOME MEASURES: Subjects were assessed on two occasions during a six-week
      period. Standardized tests were used to measure unilateral visual neglect,
      sustained and selective attention and balance. Fall histories were collected by
      chart review and semi-structured interview. RESULTS: At the initial assessment
      six subjects had sustained auditory attention deficit, eight had deficits of
      auditory selective attention, 12 had visual selective attention deficits and
      seven subjects presented with visual inattention. Scores for visual inattention
      and visual selective attention improved over time (p = 0.006, p = 0.026
      respectively) as did scores for balance control (p = 0.001). Auditory selective
      attention scores at the first assessment were found to correlate with measures of
      balance (p < 0.01), subjects with normal attention scores achieved better balance
      scores. Four subjects fell at least once during the six weeks. Scores for
      attention and balance of fallers were not found to be significantly different
      from the scores of nonfallers. CONCLUSIONS: The sample size was small but high
      levels of attention deficit were identified. Findings suggest a weak or no
      relationship between attention deficits and falls. Further studies are required
      to explore the extent of attention deficits post stroke and its impact on balance
      control and falling.

PMID- 11518446
TI  - Bobath or Motor Relearning Programme: a continuing debate.

PMID- 11518447
TI  - Chlamydia trachomatis and male infertility in Tunisia.
AB  - OBJECTIVE: Chlamydia trachomatis is a common sexually transmitted micro-organism.
      The impact of chlamydial infection on semen parameters and male fertility is
      controversial. Our purpose was to determine the prevalence of C. trachomatis in
      the male partners of infertile couples in Tunisia and to assess the relationship
      between chlamydial infection markers and male infertility. METHODS: Chlamydial
      DNA in urethral and in semen specimens was determined by using the Cobas Amplicor
      polymerase chain reaction (PCR) assay and chlamydial immunoglobulin G (IgG)
      antibodies were measured by micro-immunofluorescence in serum samples in 92 male
      partners, with or without pathological standard semen parameters, according to
      the guidelines of the World Health Organization (sperm count, progressive sperm
      motility, sperm morphology and sperm viability). In parallel, chlamydial
      infection markers in endocervical material were determined by PCR and chlamydial
      IgG antibodies were measured by micro-immunofluorescence in serum samples from
      the female partners of the patients. RESULTS: C. trachomatis was found in 35.9%
      (33/92) of the male partners of the infertile couples and in 38% (35/92) of their
      female partners. There was a significant correlation between the detection of C.
      trachomatis in both partners (p = 0.004). C. trachomatis DNA was detected in
      18.5% (17/92) of urethral specimens and in 16.3% (15/92) of semen specimens.
      Chlamydial IgG antibodies were present in 9.8% (9/92) of the serum samples. A
      standard semen analysis showed that 88% (81/92) were pathological. Sperm
      viability, progressive sperm motility, morphology and sperm concentration were
      abnormal in 73.8%, 70.2%, 34.5% and 13%, respectively, of the 92 evaluated semen
      specimens. Comparison of the parameters of the standard semen analysis between
      the male partners of the infertile couples with or without chlamydial infection
      markers showed that only the presence of C. trachomatis DNA in semen samples can
      affect sperm motility. Parameters of the standard semen analysis were not
      significantly related either to the detection of chlamydial DNA in urethral
      samples or to the presence of serum chlamydial antibodies. CONCLUSION: Our
      results show that C. trachomatis seems to be widespread among the male partners
      of infertile couples in Tunisia and show that this organism can affect sperm
      motility and, thus, can play an important role in the etiology of male
      infertility.

PMID- 11518448
TI  - A large observational clinical evaluation of a desogestrel-containing combiphasic
      oral contraceptive in Germany.
AB  - OBJECTIVE: The aim of this observational study was to assess the influence of a
      new combiphasic oral contraceptive on cycle control, tolerability and acne in a
      large cohort of women who wanted to switch from their previous oral
      contraceptive. METHODS: A total of 2,280 women were enrolled in this clinical
      evaluation at 232 centers in Germany. All women switched from their previous pill
      to a combiphasic oral contraceptive containing ethinylestradiol and desogestrel
      (combiphasic EE/DSG; comprising 25 microg desogestrel and 40 microg
      ethinylestradiol for 7 days followed by 125 microg desogestrel and 30 microg
      ethinylestradiol for 15 days and then a 6-day pill-free interval) for three
      cycles. RESULTS: Most women (53%) had previously used a monophasic oral
      contraceptive containing 20 or 30-35 microg ethinylestradiol. The most frequent
      reasons for switching were bleeding irregularities (41% of women), other
      menstrual disorders (27%) and migraine/headache (10%). After switching to
      combiphasic EE/DSG, cycle control improved significantly: the incidences of
      spotting and breakthrough bleeding decreased from 33% and 23% of women,
      respectively, before the start of the study, to 7% and 3% of women at the end of
      the study period. At the end of the study, acne was no longer present in 37% of
      the 592 women who had acne at the start of the study, and subjective complaints
      such as headaches were less frequent than before. Most women were satisfied or
      very satisfied with the combiphasic oral contraceptive and 89% wished to continue
      using it. CONCLUSIONS: The results of this observational clinical evaluation
      indicate that in everyday use, for women who wish to switch from another oral
      contraceptive, combiphasic EE/DSG is an effective and well-tolerated oral
      contraceptive, which improves cycle control and has a beneficial effect on acne.

PMID- 11518449
TI  - Chlamydia trachomatis infections--a major concern for reproductive health. Where
      do we stand regarding epidemiology, pathogenesis, diagnosis and therapy?
AB  - The current article deals with the problem of distinguishing between relapse and
      reinfection of genital chlamydial infections due to the chronic character of such
      infections. The problem of detecting and treating chlamydial pelvic inflammatory
      disease is considered. Factors that may affect the clinical presentation of such
      infections, such as hormonal therapy, are also highlighted. Observations on novel
      manifestations of Chlamydia trachomatis infections, such as spontaneous abortion,
      prematurity and intrauterine infections as well as a statistical correlation of a
      certain serovar to cervical cancer, are described. The representivity of the data
      on infections with C. trachomatis monitored in national surveillance programs is
      questioned. The paper also elaborates on which type of sample, sample site and
      detection method may be optimal for the diagnosis of such infections in women.
      Whether to screen at clinics and self-sampling at home of specimens from an index
      case and a sexual partner to be mailed to a laboratory for testing is discussed.
      Whether or not females are more susceptible to genital chlamydial infections and
      their sequelae than males is also discussed. The effectiveness of recommended
      antibiotic regimens is considered, e.g. in relation to the recent detection of
      the existence of strains of C. trachomatis that show heterotypic resistance to
      drugs commonly used for their treatment.

PMID- 11518450
TI  - The need for more active promotion of emergency contraception.

PMID- 11518451
TI  - The effects of two progrestogen-only pills containing either desogestrel (75
      microgram/day) or levonorgestrel (30 microgram/day) on carbohydrate metabolism
      and adrenal and thyroid function.
AB  - OBJECTIVE: To compare the effects of two progestogen-only pills, containing
      either desogestrel or levonorgestrel, on carbohydrate metabolism, and adrenal and
      thyroid function. METHODS: In a double-blind, randomized, multicenter study in
      Finland, 84 healthy female volunteers received either desogestrel 75 microg/day
      or levonorgestrel 30 microg/day for seven treatment periods of 28 days. The
      following laboratory parameters were measured at screening, and at treatment
      periods 3 and 7: carbohydrate metabolism (glucose, insulin, glycosylated
      hemoglobin (HbA1C)), adrenal function (total cortisol, cortisol binding globulin
      (CBG), dehydroepiandrosterone sulfate (DHEAS)), thyroid function (thyroid
      stimulating hormone, free thyroxine). RESULTS: Overall, the effect on
      carbohydrate metabolism was minimal with both study medications. There was a
      trend for higher glucose and insulin values for the levonorgestrel group at both
      treatment periods 3 and 7. None of the changes were thought to be clinically
      relevant. Both preparations had similar small effects on HbA1C values, indicating
      that carbohydrate metabolism was not affected. No effects were found on thyroid
      function parameters or DHEAS in either treatment group; however, total cortisol
      and CBG were slightly higher with desogestrel than with levonorgestrel. These
      changes were not considered to be clinically relevant. Both treatments were well
      tolerated. CONCLUSIONS: The effects of both progestogen-only pills on
      carbohydrate metabolism were minimal and considered to be clinically
      insignificant. With regard to adrenal and thyroid function, the effects of
      desogestrel were not significantly different from those of levonorgestrel.

PMID- 11518452
TI  - Differentiation in contraceptive behavior of the female population in Thrace,
      Greece.
AB  - OBJECTIVE: To investigate the factors influencing the contraceptive practice of
      the female population in the rural area of Thrace, Greece. METHODS: We conducted
      a retrospective sociopsychological study on representatives of the two major
      religious subgroups in Thrace: 127 Orthodox Christians and 120 Muslims. The women
      were reasonably representative in terms of age, education, marital status and
      professional life. Interviews covered sexual history and contraceptive use in
      detail. RESULTS: We observed a significant preference of Christians for condoms,
      and of Muslims for coitus interruptus. The use of the male condom was
      significantly higher in younger, compared to older, Christians (p < 0.001).
      Muslim women aged 30-39 years showed a significant preference for coitus
      interruptus and intrauterine devices, as compared with Christians. Highly
      educated women of both subgroups did not present statistically significant
      differences concerning contraception. It was found that, the more intense the
      sexual activity, the more common the use of the condom for Christians and the
      more popular the choice of interrupted intercourse for Muslims. Muslims with a
      permanent sexual relationship preferred interrupted intercourse, while all
      Muslims with multiple sexual partners used the male condom. CONCLUSIONS: There is
      an urgent need to promote information concerning the variety of modern
      contraceptive options in order to improve the prevalence of contraceptive use and
      reproductive health in the region of Thrace.

PMID- 11518453
TI  - Attitudes and practices of pharmacists towards emergency contraception in Durban,
      South Africa.
AB  - Emergency contraception, which is used to prevent pregnancy following unprotected
      intercourse, could prove invaluable to a country like South Africa which has high
      fertility and pregnancy rates. However, the success of emergency contraception is
      dependent on the awareness, knowledge, attitudes and practices amongst health
      care providers and the public towards it. The aim of this study was to assess the
      attitudes and practices of community pharmacists towards emergency contraception.
      The study was conducted in North and South Central Durban, South Africa. This
      questionnaire-based study sought from pharmacists the frequency of demand and
      supply of emergency contraception, as well as their attitudes and practices
      towards it. The sample included all 182 pharmacies located in the study area. A
      total of 96% of pharmacists had received requests for emergency contraception
      within the last year. On average, each pharmacist received 177 requests for
      emergency contraception. Sixty-nine per cent of pharmacists were in favor of
      making emergency contraceptive pills available without a prescription, 62% were
      already supplying emergency contraceptive pills without a prescription and 67%
      felt that it was important to increase public awareness regarding emergency
      contraception. Ninety-one per cent of pharmacists did not have any literature
      regarding emergency contraception to hand to clients, 68% had a private area in
      their pharmacy to counsel patients and 86% of pharmacists indicated that they
      discussed long-term contraception with clients. This study is the first in South
      Africa aimed at determining the utilization of emergency contraception. However,
      further studies are required in order to ascertain information that will assist
      in changing current health policies to improve those in reproductive health care.

PMID- 11518454
TI  - Treatment of menorrhagia with a novel 'frameless' intrauterine levonorgestrel
      releasing drug delivery system: a pilot study.
AB  - OBJECTIVE: To evaluate the effect on menstrual blood loss of a novel 'frameless'
      intrauterine drug delivery system, the FibroPlant levonorgestrel intrauterine
      system (IUS), releasing 14 microg of levonorgestrel/day. An ancillary objective
      was to evaluate the contraceptive performance. STUDY DESIGN: This was an open
      label, non-comparative ongoing pilot study. Thirty-two insertions were performed
      in fertile women aged between 31 and 51 years for the treatment of menorrhagia,
      as well as for contraceptive purposes. Fifteen women who developed excessive
      bleeding were fitted with the FibroPlant levonorgestrel IUS immediately following
      the removal of a copper-bearing intrauterine device (IUD), the GyneFix IUD. To
      discriminate between menorrhagia and normal menstrual blood loss, women were
      evaluated using a simple visual assessment technique. The trial covered a period
      from a minimum of 1 month up to 23 months. RESULTS: At the time of study
      analysis, the total number of woman-months was 361. Fourteen of the women had had
      the FibroPlant levonorgestrel IUS in place for more than 1 year, and 29 women for
      6 months or more. All women reported greatly reduced bleeding. However, no cases
      of amenorrhea resulting from endometrial suppression were encountered. The
      reduction of bleeding was substantial after 1 month of treatment and decreased
      further over the next months to remain stable thereafter. The mean bleeding score
      before treatment was 338 (range 185-740) in the group who had had no prior use of
      an IUD and 368 (range 185-890) in the group with prior IUD use. The mean bleeding
      score dropped to a mean score of 70 (range 5-210) in the 'no prior IUD use' group
      and to a mean score of 52 (range 3-150) in the 'prior IUD use' group, after 1-23
      months of follow-up. This result is highly statistically significant (p < 0.001).
      There were no statistical differences in bleeding scores before and during
      treatment between the two groups of women, with or without prior use of the
      copper IUD. Significant spotting was rare after the first 3 months following
      insertion. No complications (e.g. infection, expulsion or perforation) or
      pregnancies occurred. The FibroPlant levonorgestrel IUS was well tolerated by all
      women involved in the study and no systemic hormonal side-effects were reported.
      CONCLUSION: The FibroPlant levonorgestrel IUS is effective in significantly
      reducing the amount of menstrual blood loss in women with menorrhagia. Strong
      endometrial suppression is the principal mechanism explaining both the effect on
      menstrual blood loss and the contraceptive performance of the IUS. There were no
      differences in bleeding scores before and during treatment between the two groups
      of women with or without prior use of the copper IUD, suggesting that the
      development of heavy bleeding was not related to the use ofthe IUD. The
      therapeutic effect of this contraceptive method is highly desirable, particularly
      in women with heavy bleeding or anemia in developing countries, as other
      treatment modalities are less effective, more costly, more invasive or
      inaccessible. The low daily release rate of levonorgestrel from the FibroPlant
      levonorgestrel IUS results in a low incidence of hormonal side-effects and
      reduces the likelihood of amenorrhea. The simple design characteristics and
      revolutionary anchoring system minimize the occurrence of complaints of pain and
      the incidence of expulsion.

PMID- 11518455
TI  - Values of electroretinogram responses according to axial length.
AB  - Accurate interpretation of electroretinograms (ERGs) requires knowledge of
      effects of axial myopia on ERG responses. Our purpose was to derive expected
      changes of ERG responses according to axial length, to stimulus conditions that
      conform to the International Society for Clinical Electrophysiology of Vision
      (ISCEV) Standard for Electroretinography. ERGs from 60 subjects were recorded.
      The subjects were assigned to one of three groups according to the level of
      myopia. Thirty-three subjects had high myopia (-6.00 D to -14.50 D; mean age, 31
      years), eight had mild myopia (-3.00 D to -5.00; mean age, 28 years), and 19 had
      a small refractive error (+0.75 D to -2.75 D; mean age, 27 years). No subjects
      had myopic retinopathy. Stimulus-response curves were fitted to dark-adapted b
      wave amplitudes and maximum amplitude and semi-saturation constants derived.
      Axial lengths, measured with A scan ultrasound, ranged from 22.2 mm to 30.0 mm.
      Analysis of variance and post hoc t-tests revealed significant difference between
      subjects with high myopia and subjects with small refractive error for ERG
      amplitude data. There were no significant differences between the three groups
      for implicit times, the ratio of b- to a-wave and semi-saturation constant. There
      is linear reduction in the logarithmic transform of ERG amplitude with increasing
      axial length, related more to axial length than refractive error. We provide
      relative slope and intercept values, allowing labs to derive expected ERG
      amplitudes according to axial length. These derivations are valid for persons
      with no retinopathy.

PMID- 11518456
TI  - The impact of fixation on the multifocal electroretinogram.
AB  - There are a number of variables which can influence the quality of multifocal ERG
      waveforms. In common with visual field measurements, fixation quality may be an
      important parameter on the integrity of the acquired data. A low cost, fixation
      monitoring device was used to assess fixation quality on a group of normal
      volunteers. Data was successfully acquired while five subjects viewed a fixation
      target for a period of time equal to that of a single multifocal recording
      segment. The target was presented on a stationary grey background and as the
      central fixation mark on a 61-element multifocal flicker stimulus. The results
      show no significant difference with or without the flickering pattern. The
      percentage of samples falling within 1.2 degrees of the point of fixation was
      51%. This suggests that fixation quality is adequate for scaled stimuli where the
      central element subtends 2.4 degrees. High resolution stimuli of less than 2.4
      degrees may be more susceptible to fixation fluctuations during the recording
      process.

PMID- 11518457
TI  - Adaptation dynamics in pattern-reversal visual evoked potentials.
AB  - Recording a VEP usually involves prolonged repetitions of the stimulus, but the
      influence of adaptation is rarely discussed in this context. Two experiments were
      performed. In Experiment 1 the time course of the response amplitude during
      steady-state stimulation was assessed. During the first seconds of stimulation we
      found an increase in amplitude, followed by a continuous exponential decline.
      This confirmed earlier results. There is considerable inter-subject variability
      concerning all aspects of the time course in our 19 subjects. Experiment 2 used
      two types of transient pattern reversal stimuli: one regular stimulus as used in
      standard clinical applications and one with a pause in between each reversal. N1
      and P1 amplitudes did not show significant differential effects. N2 amplitude was
      reduced by 73% in the standard condition whereas P1 peak time increased slightly
      but significantly (3.2 ms).

PMID- 11518458
TI  - A physiological basis for definition of the ISCEV ERG standard flash (SF) based
      on the photopic hill.
AB  - The ISCEV Standard for Clinical Electrophysiology indicates that the ERG standard
      flash should be defined within a very narrow range of intensities. Yet no
      information is provided as to how this intensity range was identified. We present
      evidence that would support a redefinition of the SF based on known photopic ERG
      properties.

PMID- 11518459
TI  - Do P1 and N1 evoked by the ERP task reflect primary visual processing in
      Parkinson's disease?
AB  - OBJECTIVES: To evaluate whether P1 and N1 evoked by ERP tasks could appropriately
      reflect primary visual processing in Parkinson's disease (PD). METHODS: We
      recorded ERPs in 13 PD patients with duration of illness less than 5 years and 18
      age-matched normal control subjects. P1 and N1 from Oz were evoked by a visual
      oddball and a delayed matching S1-S2 task. The effect of different events on P1
      and N1 was studied. All patients were given an ECD-SPECT examination, and the
      SPECT images were overlaid on the 3D-MRI. The correlation of P1 or N1 to the
      regional cerebral blood flow (rCBF) was studied. RESULTS: P1 was not influenced
      by different events. There was no significant P1 differences between the PD and
      the normal group. N1 was significantly shorter and smaller in the patients than
      that in the normal group. N1 amplitude after the waveform subtraction (target
      frequent) in the PD group did not show significant difference with that in the
      normal controls, nor with the N1 before the subtraction. Nd, the subcomponent of
      N1 after the subtraction in the patients was significantly earlier and smaller
      than that in the normal controls. P1 only weakly correlated with the rCBF in the
      occipital lobe. N1 was correlated with the rCBF in a global region. CONCLUSIONS:
      The results provided some evidence that P1 might reflect the primary visual
      processing, and N1 might be involved in both primary and cognitive visual
      processing. The altered N1 in the PD patients might be due to the deformed Nd.

PMID- 11518460
TI  - A comparison of CRT and digital stimulus delivery methods in the multifocal ERG.
AB  - The purpose of this paper is to compare and evaluate the multifocal ERG response
      from raster based CRT and Digital Projection (LCD) stimulus delivery systems. A
      custom built p.c. based multifocal system was used to generate a 61 hexagonal
      element stimulus array. The stimulus was presented on a high luminance CRT
      display and on a back projected screen using a Digital polysilicon projection
      system. A fast response photodiode was used to analyse the stimulus pulse
      characteristics of both systems. A number of recordings were performed to assess
      the effect of stimulus delivery on a standard m-sequence response, inserted full
      field filler response and on separation of onset and offset components. The pulse
      width for a CRT system is dependant on the type of phosphor and is typically 2
      msec whereas the Digital Projection system produces a 13.3 msec pulse equivalent
      to the frame rate for the system. Slowing down the m-sequence by a factor of
      eight results in a pulse width of 106 msec which should enable the recovery of
      true offset responses. The CRT stimulus consists of a series of eight pulses of 2
      msec duration each separated by 11.3 msec. First order responses are larger from
      the CRT system and second order responses larger from the Digital system. In
      conclusion, there are fundamental differences in the two delivery systems. The
      CRT system may have more potential in examining non-linear aspects of the
      multifocal response. Although both systems may be able to record offset
      responses, the Digital system will generate true offset responses whereas the CRT
      system may not allow true separation of these components.

PMID- 11518461
TI  - Contralateral breast cancer: molecular differentiation between metastasis and
      second primary cancer.
AB  - Previous cancer in one breast is a strong known risk factor for cancer in the
      contralateral breast. Differences in tumor histology and nuclear grading are
      applied to distinguish between a metastatic spread and a second primary cancer,
      although cancers of the breast often share the same histological features.
      Comparison of genetic alterations in paired tumors may provide the most reliable
      approach for discerning clonal relationships, hence uncovering the presence or
      absence of multiple primary cancers. We compared tumors from 33 patients with
      cancer in both breasts for mutations in the p53 gene. With this molecular
      approach, we were able to define the relationship within paired tumors in 13
      patients. The paired tumors of two patients shared the same mutation, revealing
      the second lesion in one case as a contralateral metachronous lymph node
      metastasis appearing 29 months after first surgery, and in the other as a spread
      to the opposite breast. In 11 patients, mutations were either discordant or
      solely present in one of the lesions, confirming the diagnosis of bilateral
      breast cancer. Histopathological evaluation had failed to provide firm diagnosis
      in nine out of 11 instances on account of concordances in pathological parameters
      such as histological type and grading. In our study, we could show that bilateral
      breast malignancies most frequently represent two primary breast cancers. We
      could also demonstrate that contralateral breast cancer spread does occur.
      Standard pathological assessment allowed a firm diagnosis only in the presence of
      different histological types.

PMID- 11518462
TI  - p27 expression correlates with short-term, but not with long-term prognosis in
      breast cancer.
AB  - New prognostic and predictive factors are needed to adjust more appropriate
      therapy for individual patients after operation. p27 is a cell cycle regulator,
      and a low tissue expression of this protein has been shown to correlate with poor
      prognosis in colorectal, lung, gastric, prostate, and breast cancer. In this
      study on 197 breast cancer patients with a median follow-up of 17 years, the
      prognostic value of immunohistochemical p27 expression was evaluated. After 5
      years of follow-up patients with a p27 expression in less than 50% of the tumor
      cells had a significantly lower survival rate than those with an expression above
      this level (p = 0.01). However, after longer follow-up the difference decreased
      and was no longer significant at 7 years (p = 0.1) or when the entire follow-up
      period was examined (p=0.67). Tests for associations showed that a low p27
      expression correlated with a high histologic grade, a high S-phase fraction
      (SPF), an advanced TNM stage and negative hormone receptor status. IN CONCLUSION:
      Tissue expression of p27 is a significant predictor of 5-year, but not of 10- or
      15-year breast cancer specific survival.

PMID- 11518463
TI  - Inhibition of human breast cancer cell growth by blockade of the mevalonate
      protein prenylation pathway is not prevented by overexpression of cyclin D1.
AB  - Overexpression of the cyclin D1 (CCND1) gene, encoding a downstream effector of
      mitogenic signals that plays a central role in G1 phase progression, is often
      found in cancerous cells. In sporadic breast cancer (BC), this is one of the most
      frequent and early genetic lesions identified so far, found in more than 50% of
      the tumors. Inhibitors of the mevalonate/protein prenylation pathway belong to a
      new family of cancer therapeutic agents that act by blocking intracellular
      mitogenic signal transduction pathways, thereby preventing expansion of pre
      cancerous foci and inhibiting growth of transformed cells. It is not known at
      present whether constitutively high intracellular levels of cyclin D1 might
      interfere with the cytostatic actions of mevalonate/protein prenylation
      inhibitors. This possibility was investigated here by assessing the cell cycle
      effects of Simvastatin, a non-toxic upstream inhibitor of the mevalonate pathway,
      on human BC MCF-7 cells expressing either normal or enhanced levels of cyclin D1
      from of a stably transfected, tet-inducible expression vector. Results show that
      constitutive overexpression of this protein, such as that found in sporadic BCs,
      does not influence the growth inhibitory effects of Simvastatin in vitro. In
      addition, D1-overexpressing embryo fibroblasts were also found to be responsive
      to the cell cycle effects of mevalonate/protein prenylation pathway blockade,
      further suggesting that high intracellular levels of cyclin D1 do not prevent the
      cytostatic actions of compounds targeting this metabolic pathway.

PMID- 11518464
TI  - Incidence of second primary breast cancer among women with a first primary in
      Manitoba, Canada.
AB  - Second primary breast cancer is of importance because of the increasing incidence
      of first primary breast cancer and improved survival. There is lack of
      information on the disease in Canada. We studied 14,220 women with a first
      primary breast cancer (invasive only) diagnosed during the period from 1970 to
      1997, in Manitoba, Canada. A breast cancer was considered to be a second primary
      if it was an invasive lesion diagnosed at least six months after the diagnosis of
      an initial primary breast cancer. The incidence rate of second primary breast
      cancer was approximately six per 1,000 person-years, and the cumulative incidence
      during the 28-year study period was 14.3%. Average age at diagnosis of first
      primary breast cancer had increased significantly since 1970. The incidence was
      higher in 1975-1979, and there was no significant difference among other study
      periods after adjustment for the age at diagnosis of first primary breast cancer.
      Standardized incidence ratios showed no significant difference among six age
      groups after adjusting for calendar year. However, women with a first primary
      breast cancer had an increased risk of developing a second primary breast cancer
      compared with the risk of developing a first primary breast cancer among the
      general female population. The SIR was markedly greater among women who had a
      first primary breast cancer before the age of 40 years, and decreased
      significantly with increasing age at diagnosis of first primary breast cancer.
      The data provide epidemiological information on second primary breast cancer risk
      for the general female population in Manitoba, Canada.

PMID- 11518465
TI  - Predictability of monthly and yearly rhythms of breast cancer features.
AB  - In order to evaluate if breast cancer biological characteristics undergo
      significant menstrual and seasonal variations, we analysed in a consecutive
      series of 905 breast cancer patients, steroid receptor level (ER and PgR by DCC
      assay), proliferative activity (3H-Thymidine Labeling Index, 3H-TLI) and size of
      primary tumour in relation to calendar date and day of menstrual cycle at the
      time of the surgical procedure. For data analysis, the method of time series
      construction and classical spectral analyses with Bartlett Kolmogorov-Smirnov
      test for white noise (BKS test) was utilised. For what concerns menstrual
      variations, 3H-TLI showed a significant periodicity (t = 0.3146, p < 0.01 by BKS
      test) with peaks at day 12nd and day 18th; ER showed a significant periodicity (t
      = 0.3605, p < 0.01 by BKS test) with more evident peak at day 27th; PgR, a
      significant periodicity (t = 0.160, p = 0.05 by BKS test) with peaks at day 15th
      and day 24th, similar to that observed for tumour size (t = 0.19, p < 0.05 by BKS
      test). With respect to yearly fluctuations, 3H-TLI showed only a trend for a
      significant rhythm (t = 0.16, p = 0.06 by BKS test) with peaks in May and
      November; ER a significant periodicity (t = 0.2099, p < 0.05 by BKS test) with
      two evident peaks in January and April; also for PgR a significant periodicity (t
      = 0.3161, p < 0.05 by BKS test) was demonstrated with a peak in July; finally,
      tumour size showed a significant rhythm (t = 0.335, p < 0.01) paralleling 3H-TLI
      behaviour. Finally, the analysis of variance with interaction of menstrual and
      seasonal timings showed that only the seasonal timing was able to independently
      influence the 3H-TLI variations (3H-TLI higher in spring). We confirmed that
      breast biology has significant menstrual and seasonal variations and that the
      seasonality is probably the timing factor more relevant in periodicity
      determination.

PMID- 11518466
TI  - Low pO2 and beta-estradiol induce VEGF in MCF-7 and MCF-7-5C cells: relationship
      to in vivo hypoxia.
AB  - Previous work from this laboratory demonstrated that MCF-7 breast carcinoma cells
      grown in nude mice contained minimal hypoxia but that tamoxifen treatment of
      these tumors resulted in increased hypoxia (Evans S. et al., Cancer Research,
      1997). These findings led to studies exploring the link between estrogen
      signaling and tumor oxygenation and determining the role of VEGF in this process.
      The stimulation of estrogen-dependent MCF-7 breast carcinoma cells in vitro with
      beta-estradiol resulted in a two-fold induction of VEGF mRNA and 1.3-2-fold
      increase in protein, similar to what was observed when these cells were exposed
      to 0. 1% oxygen. Furthermore, the two stimuli given together had an additive
      effect on (increasing) VEGF expression, suggesting that the combination of
      hypoxia and estrogen may be important in upregulating VEGF in some breast
      cancers. Estrogen-independent MCF-7-5C cells, developed by growing MCF-7 cells in
      long-term culture in estrogen-free media, were also studied. Using EF5, a
      fluorinated 2-nitroimidazole which localizes to hypoxic cells, MCF-7-5C tumors
      grown in nude mice were found to contain lower pO2 levels and more hypoxic
      regions than similarly grown MCF-7 tumors. We tested the hypothesis that this
      might be the result of defective expression of VEGF in MCF-7-5C cells in response
      to beta-estradiol and/or hypoxia. However, MCF-7-5C and MCF-7 cells showed a
      similar induction of VEGF in vitro in response to either beta-estradiol or
      hypoxia. Therefore, although these two cell lines grown as tumors have
      substantial differences in the presence and patterns of hypoxia, this could not
      be explained by a difference in VEGF induction.

PMID- 11518467
TI  - Overexpression of the p16 cell cycle inhibitor in breast cancer is associated
      with a more malignant phenotype.
AB  - In order to study the role of the p16INK4A(MTS1/CDKN2a) tumor suppressor in
      breast cancer, we analyzed p16 protein expression in 60 breast cancer samples
      which were also analyzed for expression of Rb, Ki67, HER2/neu, and estrogen and
      progesterone receptors (ER, PR). P16 expression was investigated by two methods:
      western blotting (WB) followed by densitometry, and immunohistochemistry (IHC).
      The Rb status was studied by western blotting, and expression of Ki67, HER2/neu,
      ER, and PR was analyzed immunohistochemically. P16-negative results were found in
      18% of the carcinomas by WB, but in only one case by IHC and were not associated
      with established prognostic parameters. In contrast, p16 overexpression which was
      detected by WB and IHC in 15% and 25% of the tumors, respectively, was
      significantly associated with unfavorable prognostic indicators. High p16
      expression as detected by both methods correlated significantly with high grading
      and a negative estrogen receptor status. In addition, a significant association
      of p16 staining with inverse progesterone receptor status and high Ki67
      expression was found with IHC. No correlation of p16 expression with clinical
      stage, HER2/neu immunostaining, Rb expression or Rb phosphorylation was found.
      Comparison of western blot results and immunohistochemistry suggests that both
      nuclear and cytoplasmic immunoreactivity in tumor cells is specific and due to
      p16 expression. We conclude that high p16 reactivity (both nuclear
      andcytoplasmic) is indicative of a more undifferentiated, malignant phenotype in
      mammary carcinomas.

PMID- 11518468
TI  - Induction of anti-mammary cancer immunity by engaging the OX-40 receptor in vivo.
AB  - The OX-40 receptor (OX-40R) is a member of the tumor necrosis factor receptor
      (TNF-R) superfamily that is expressed on activated CD4+ T cells. The OX-40R is a
      costimulatory molecule that induces CD4+ T cell activation when engaged by its
      ligand (OX-40 L; found on antigen presenting cells). In human and murine tumors,
      we have shown upregulation of the OX-40R on CD4+ T cells from tumor-infiltrating
      lymphocytes (TIL) and tumor-draining lymph node cells (TDLNC) but not on systemic
      CD4+ T cells, such as peripheral blood lymphocytes (PBL) or splenocytes. In order
      to examine potentially heightened anti-tumor immunity through enhanced
      costimulation when engaging OX-40R in vivo, we inoculated mice with a murine
      mammary cancer cell line (SM1) and then treated with a soluble form of the OX-40
      L. Mice injected with a lethal inoculum of SM1 cells were given two
      intraperitoneal injections (days 3 and 7 post-inoculation) of 100 microg soluble
      OX-40 L. Seven of 28 treated mice survived the lethal tumor inoculum, as compared
      to one of 28 control mice, demonstrating a significant survival benefit with
      treatment (p = 0.0136, log rank analysis). Mice that did not develop tumor by day
      90 were rechallenged; all remained tumor-free. Mice were also injected with a
      second mammary tumor line (4T1) and treated with OX-40L:Ig with similar
      therapeutic results. Activation of OX-40R+ CD4+ T cells during mammary cancer
      priming stimulated an antitumor immune response resulting in enhanced survival
      and protective anti-tumor immunity. These results should have practical
      applications for treatment modalities for patients with breast cancer.

PMID- 11518469
TI  - Expression of heparin-binding epidermal growth factor-like growth factor in
      breast carcinoma.
AB  - The expression of heparin-binding epidermal growth factor-like growth factor (HB
      EGF) was investigated for 76 cases of breast carcinoma. HB-EGF was expressed in
      71.8% of the carcinoma cases but only slightly in normal mammary glands.
      Interestingly, its expression was inversely related to biological aggressiveness
      of the breast carcinoma. These results suggest that HB-EGF may play a crucial
      role in the early stage of this carcinoma.

PMID- 11518470
TI  - Sealing of postoperative axillary leakage after axillary lymphadenectomy using a
      fibrin glue coated collagen patch: a prospective randomised study.
AB  - Seroma formation after axillary lymphadenectomy in women with breast cancer
      remains a problem despite many efforts to reduce surgery-related morbidity. In a
      prospective, randomised, open, parallel-group, controlled clinical trial we
      evaluated the effect of a fibrin-glue coated collagen patch (TachoComb H, Nycomed
      Pharma AS, Denmark) on volume and duration of postoperative axillary drainage,
      duration of hospital stay, and procedural safety. Sixty patients were included in
      the study. Patients did not differ with respect to general characteristics, such
      as age, body mass index, treatment modality, and tumor stage distribution. In 29
      patients, a fibrin-glue coated collagen patch was applied from the apex axillae
      to the thoracic longus nerve and half a patch was applied to the lateral border
      of the axillary nerve-vessel bundle. Thirty-one patients were randomised to
      standard closure of the axillary lymphadenectomy area. The mean duration of
      axillary drainage was 3.8 +/- 1.9 days in the fibrin-glue treatment group and 3.9
      +/- 1.8 days in the control group (p = NS). The mean total drainage volume was
      338.5 +/- 251.8 ml in the fibrin-glue treatment group and 370.8 +/- 314.6 ml in
      the standard closure group (p = NS). The mean length of post-operative hospital
      stay was 9.1 +/- 2.7 days in the fibrin-glue treatment group and 9.3 +/- 3.6 days
      in the standard closure group (p = NS). Seven patients (25%) and eight patients
      (25%) were diagnosed with local inflammation in the fibrin-glue treatment group
      and the standard closure group, respectively (p = NS). Seroma formation after
      drain removal was found in 11 patients (39%) in the fibrin-glue treatment group
      and in 13 patients (42%) in the standard closure group (p = NS). In summary, we
      observed no statistically significant differences with respect to axillary
      drainage time, drainage volume, length of hospital stay, local inflammation, and
      seroma formation after drainage removal.

PMID- 11518471
TI  - Lithium augmentation in depressive patients not responding to selective serotonin
      reuptake inhibitors.
AB  - This communication reviews current literature on lithium augmentation in patients
      not responding to SSRIs, giving some recommendations at the end. A significant
      proportion of depressive patients do not respond to a first antidepressive
      treatment independently of the class of drugs used. During the last 10 years,
      there have been several case reports published about open and controlled studies
      on the use of lithium augmentation in patients who were non-responders to SSRIs,
      including citalopram, fluoxetine, paroxetine and sertraline. The main underlying
      hypothesis is a synergistic effect between SSRIs and lithium, which both act on
      serotonergic neurotransmission. The available studies vary considerably in
      methodology. There are insufficient results available to confirm a rapid
      improvement (within 24-48h) after introduction of lithium, but most studies show
      substantial effects after 1 - 2 weeks, and some after 6 weeks. There is as yet no
      more clear evidence for a pharmacokinetic interaction between lithium and SSRIs
      with pharmacodynamic consequences. In conclusion, present evidence suggests that
      a lithium augmentation in depressive patients who do not respond to SSRIs may be
      an efficacious and generally well tolerated treatment, with a response rate of at
      least 50% after a period lasting 1 - 2 weeks. However, special care is indicated
      when treating elderly patients, where the risk of adverse effects is higher.

PMID- 11518472
TI  - Survey on the usefulness of trazodone in patients with PTSD with insomnia or
      nightmares.
AB  - BACKGROUND: Trazodone is commonly used in the treatment of insonmia and
      nightmares in patients with PTSD. There is little evidence in the literature for
      this practice. METHOD: Seventy-four patients from the Palo Alto Veterans Affairs
      Health Care System in California who were admitted to a specialized 8 week
      inpatient treatment program for PTSD were surveyed regarding their use of
      trazodone in the treatment of insomnia or nightmares. Patients were asked to
      complete a questionnaire regarding trazodone's effectiveness, side effects, and
      optimal doses. RESULTS: Of 74 patients surveyed, 60 patients were able to
      maintain an effective dose of trazodone. The other 14 patients were unable to
      tolerate the medication. Seventy-two percent of the 60 patients assessed found
      trazodone helpful in decreasing nightmares, from an average of 3.3 to 1.3 nights
      per week (p<.005). Ninety-two percent found it helped with sleep onset, and 78%
      reported improvement with sleep maintenance. There was a significant correlation
      between the effectiveness in decreasing nightmares and improving sleep (r= .57, p
      < .005). The effective dose range of trazodone for 70% of patients was 50 to 200
      mg nightly. Of the 74 patients surveyed, 9 (12%) reported priapism. CONCLUSION:
      Trazodone appears effective for the treatment of insomnia and nightmares
      associated with chronic PTSD. However, controlled trials are needed before any
      definite conclusions can be drawn. The higher than expected occurrence of
      priapism warrants clinicians asking directly about this side effect.

PMID- 11518473
TI  - Does lithium exert an independent antisuicidal effect?
AB  - AIM OF STUDY: Recent investigations have indicated that adequate lithium
      treatment lowers the suicide mortality associated with affective illness. One
      important question is whether the mechanism by which lithium prophylaxis may be
      effective in prolonging survival can be explained exclusively in terms of
      successful protection against the recurrence of depressive episodes, or whether
      one should consider an independent anti-suicidal factor. METHODS: We investigated
      a group of high-risk patients with recurrent affective disorders (n = 167) who
      had committed one or more suicide attempts before the start of lithium
      prophylaxis within a collaborative project by the International Group for the
      Study of Lithium Treated Patients (IGSLI). According to their recurrence-related
      response to long-term lithium prophylaxis, patients were classified into three
      groups: excellent (n = 45), moderate (n = 81) and poor responders (n = 41). Only
      depressive episodes resulting into hospitalisation were considered. A marked
      reduction in the number of suicide attempts was observed in the excellent lithium
      responders. However, we also found that over 80% of moderate responders and
      nearly 50% of poor responders did not exhibit any further suicidal behaviour
      during lithium treatment. Furthermore, we could demonstrate a significant
      reduction of suicide attempts per year as compared to a corresponding pre-lithium
      period in all three groups (0.10 vs. 0.33, 0.06 vs. 0.27, 0.02 vs. 0.26). There
      were four suicides in this high-risk group, corresponding to a suicide-related
      standardised mortality ratio (SMR) of 13.7. This contrasts sharply with an
      expected suicide SMR of approx. 100 in this population. Suicide risk was not
      related to the recurrence-preventing effect. CONCLUSION: The reduction in suicide
      attempts, in both responders and non-responders, indicates that lithium possesses
      a specific anti-suicidal effect besides its mood-stabilising property.

PMID- 11518474
TI  - Adjunctive dopamine agonists in treatment-resistant bipolar II depression: an
      open case series.
AB  - OBJECTIVE: Previous studies and case observations have suggested that dopamine
      agonists (DAAs) such as pramipexole (PPX) and ropinirole (RPN) might be effective
      for major depression, but their adjunctive use in treatment-resistant bipolar II
      depression has not yet been specifically addressed. METHOD: A chart review was
      conducted on 18 patients with a DSM-III-R bipolar NOS (Bipolar II) major
      depressive episode who were admitted to the day-hospital of the Department of
      Psychiatry at the University of Pisa. DAAs were added to ongoing treatments with
      conventional antidepressants and mood stabilizers to which patients had no
      responded after a period of at least 8 weeks. Clinical state and adverse effects
      were assessed at each visit. Final improvement in CGI scores of 1 or 2 were
      considered as responders. RESULTS: Mean DAA trial duration was 17.6 (sd = 7.8,
      range 4-34) weeks, with a mean final dose of 1.23+/-0.32 mg/day (range, 0.75
      1.50mg/day) for PPX, and 2.97+/-0.99mg/day (range, 1.50-5.00mg/day) for RPN. DAAs
      were well tolerated and did not show any negative interaction with concomitant
      psychotropic medications. Only one patient became worse (final CGI = 5), and had
      to interrupt PPX due to nausea, increased agitation and irritability. Eight
      patients (44.4%) were considered responders (4 with PPX and 4 with RPN): 5 showed
      marked improvement (CGI = 1), and 3 showed moderate improvement (CGI = 2);
      another 5 (27.8%) manifested a transient response not sustained up to the end.
      The initial and final scores of CGI severity scale for all patients (responders
      and non-responders combined) were, respectively, 5.33+/-0.7 and 3.94+/-1.3 (mean
      +/- S.D). The mean change according to the CCI severity scale was statistically
      significant (t=4.74. p < 0.0002). CONCLUSION: From the results, PPX and RPN
      appear to be well tolerated and potentially useful in the adjunctive treatment of
      drug-resistant bipolar II depression.

PMID- 11518475
TI  - Acceptance of pharmacotherapy for relapse prevention by chronic alcoholics.
AB  - The willingness to take medication is a major prerequisite for compliance with
      biological treatment approaches in psychiatric disorders. The aim of this study
      was to investigate the willingness of alcoholics to improve relapse prevention
      using drug therapy, since there has been little information about the acceptance
      of such a medication as yet. 261 chronic alcoholics consecutively referred for
      detoxification completed a newly developed questionnaire containing items on
      drinking history, recent treatments, and beliefs about drug therapy for relapse
      prevention. In order to draw comparisons, 67 self-help group attendees and 29
      alcoholics consulting an outpatient advice service were also recruited. 67.8% of
      the recently detoxified alcoholics were prepared to take medication for relapse
      prevention, if prescribed, while 60% the self-help group attendees refused drug
      therapy. There was no correlation between the acceptance of drug treatment and
      duration of dependence. Subjects willing to take a medication more often believed
      their alcoholism to be curable, and they reported a higher craving frequency. 55%
      of those willing to take a medication were willing to pay for the drugs, but in
      most cases, at a level lower than the equivalent of 5 beers. As drug therapy
      acceptance is a crucial part of compliance with, and success of medical relapse
      prevention, our results underscore the necessity of a thorough exploration into
      the health beliefs of the patient and joint development of a treatment rationale
      prior to prescription.

PMID- 11518476
TI  - Effect of a low tryptophan diet on the prolactin responses to the 5-HT2A agonist
      DOI in the rat.
AB  - Low tryptophan (TRP) diets decrease brain serotonin (5-HT) content and produce an
      up-regulation of the function of some but not all 5-HT receptor subtypes. The aim
      of the present study was to assess the effect of a two week low TRP containing
      diet on the plasma prolactin (PRL) response to the 5-HT2A receptor agonist 2,5
      dimethoxy-4-iodophenyl-2-aminopropane (DOI) in the rat. The low TRP diet
      significantly reduced plasma total TRP as well as brain 5-HT for the two weeks of
      the study although plasma free TRP was decreased only for the first week of the
      diet. The PRL response to DOI was significantly increased in the first week of
      the diet but returned to normal in the second. The results suggest that a low TRP
      diet produce a transient up-regulation of brain 5-HT2A receptors.

PMID- 11518477
TI  - Epidemiology of prescriptions for neuroleptic drugs: tranquilizers rather than
      antipsychotics.
AB  - BACKGROUND: The pharmacology of neuroleptics as well as epidemiological and
      clinical observations of prescriptions of these drugs give the impression that
      they are and can be used for indications other than schizophrenia to a
      considerable degree. METHOD: We analyzed pharmacoepidemiological data on
      neuroleptic prescriptions in Germany. We used the following criteria: numbers of
      defined daily doses (DDDs) per annum, diagnoses for which they were prescribed,
      patient age, specialist medical training of the prescribing physician, and
      indicators that neuroleptics were used instead of other psychotropic drugs such
      as minor tranquilizers. RESULTS: Only 14% of the prescriptions for neuroleptic
      drugs were for schizophrenic psychoses, 18% for other paranoid psychoses and 5%
      for affective disorders. 63% were prescribed for neurotic disorders, sleep
      disorders, or dementia. Almost half of the neuroleptic prescriptions were given
      for patients aged 65 years or over. Only 40% were prescribed by psychiatrists or
      neurologists. Throughout the period from 1986 to 1995, neuroleptic prescriptions
      increased steadily, which was paralleled by a decrease in the prescription rates
      for benzodiazepines. CONCLUSIONS: Evaluation is urgently needed for those uses of
      neuroleptic drugs that, from a pharmacoepidemiological perspective, must be seen
      as their primary indication.

PMID- 11518478
TI  - The effect of Li 1370, extract of Ginkgo biloba, on REM sleep in humans.
AB  - Ginkgo biloba extracts (GBE) have been shown to be as effective as anti
      cholinesterase inhibitors in improving the cognitive test scores of patients with
      dementia. Although it has been assumed that GBE works via its antioxidant and
      vascular effects, some evidence has emerged that GBE may have some pro
      cholinergic activity. We wished to test the hypothesis that a standardised
      preparation of GBE, Li 1370, increases cholinergic activity by measuring its
      effect on the sleep polysomnogram. In particular, latency to Rapid Eye Movement
      (REM) sleep is sensitive to cholinergic activity. For this purpose we recruited
      10 healthy volunteers of both sexes and recorded sleep polysomnograms in a
      randomised cross-over study, comparing sleep polysomnograms taken the night after
      a single evening dose of Li 1370 (240 mg) with sleep polysomnograms taken after
      an evening dose of placebo. No significant differences in sleep parameters
      (including REM sleep measures) were detected; however sleep efficiency measures
      and subjective sleep quality reports showed that Li 1370 was well tolerated.

PMID- 11518479
TI  - Subclinical pancreatitis related to mirtazapine - a case report.

PMID- 11518480
TI  - Further evidence of intact working memory in autism.
AB  - Earlier investigations have found mixed evidence of working memory impairment in
      autism. The present study examined working memory in a high-functioning autistic
      sample, relative to both a clinical control group diagnosed with Tourette
      Syndrome and a typically developing control group. No group differences were
      found across three tasks and five dependent measures of working memory.
      Performance was significantly correlated with both age and IQ. It is concluded
      that working memory is not one of the executive functions that is seriously
      impaired in autism. We also suggest that the format of administration of working
      memory tasks may be important in determining whether or not performance falls in
      the impaired range.

PMID- 11518481
TI  - Hand preference and motor functioning in children with autism.
AB  - This study examined three theories that have been proposed to explain the high
      rates of ambiguous hand preference in young children with autism. Twenty children
      with autism were matched with 20 children with developmental delays and 20
      normally developing children. The groups were compared on measures of hand
      preference and motor skills. Results indicated that the lack of development of a
      hand preference in children with autism was not a direct function of their
      cognitive delay, as the children with developmental delays showed a dissimilar
      pattern of hand preference. The lack of a definite hand preference in the
      children with autism was also not due to a lack of motor skill development, as
      the children with developmental delays displayed similar levels of gross and fine
      motor skills without the accompanying lack of a definite hand preference. The
      finding that children with autism with a definite hand preference displayed
      better performance on motor, language, and cognitive tasks than children with
      autism who did not display a definite hand preference, however, provided support
      for the bilateral brain dysfunction hypothesis.

PMID- 11518482
TI  - Obstetric complications and risk for severe psychopathology in childhood.
AB  - The purpose of the study was to assess the association of obstetric complications
      with risk for mental disorders resulting in hospitalization before the age of 15.
      Records from all births in Denmark from 1973 through 1993 were linked to records
      of all psychiatric hospitalizations. Diagnoses were grouped into seven broad
      categories. A reference population of 10% of births in Denmark from 1973 to 1990
      was used for comparison. Obstetric complications were associated with the range
      of mental disorders occurring in childhood. The strongest predictors were a
      variable indicating the interaction of birth weight with speed of growth and the
      5-minute Apgar score. There was no diagnostic group that stood out as different
      with respect to obstetric complications. These results are consistent with the
      hypothesis of the continuum of reproductive casualty.

PMID- 11518483
TI  - Facilitated communication since 1995: a review of published studies.
AB  - Previous reviews of Facilitated Communication (FC) studies have clearly
      established that proponents' claims are largely unsubstantiated and that using FC
      as an intervention for communicatively impaired or noncommunicative individuals
      is not recommended. However, while FC is less prominent than in the recent past,
      investigations of the technique's efficacy continue. This review examines
      published FC studies since the previous major reviews by Jacobson, Mulick, and
      Schwartz (1995) and Simpson and Myles (1995a). Findings support the conclusions
      of previous reviews. Furthermore, this review critiques and discounts the claims
      of two studies purporting to offer empirical evidence of FC efficacy using
      control procedures.

PMID- 11518484
TI  - Comparisons of discrete-trial and normalized behavioral language intervention for
      young children with autism.
AB  - This critical review examined a series of 10 controlled studies in which
      traditional operant behavioral procedures were compared with more recently
      developed normalized interventions for teaching language to young children with
      autism. Main characteristics of the older treatments include highly structured
      direct teaching sessions of discrete trials, teacher initiation, artificial
      reinforcers, and response shaping. Normalized interventions consist of loosely
      structured sessions of indirect teaching with everyday situations, child
      initiation, natural reinforcers, and liberal criteria for presentation of
      reinforcers. The main conclusion was that in all eight studies with language
      criterion responses, normalized language training was more effective than
      discrete-trial training. Furthermore, in both studies that assessed parental
      affect, normalized treatment yielded more positive affect than discrete-trial
      training.

PMID- 11518485
TI  - Stress in UK families conducting intensive home-based behavioral intervention for
      their young child with autism.
AB  - There is increasing international interest in intensive home-based behavioral
      intervention for children with autism. In the present study, 141 UK parents
      conducting such interventions completed a questionnaire addressing issues of
      stress, coping, and support. Regression analyses showed that parents' stress
      levels were predicted mainly by psychological rather than demographic variables.
      In particular, adaptive coping strategies, informal social support sources, and
      beliefs about the efficacy of the intervention were associated with lower
      reported stress and higher levels of autism symptomatology were associated with
      higher reported stress. There was also evidence that the use of Passive Appraisal
      coping and beliefs about the efficacy of the interventions moderated the effects
      of autism symptomatology on parents' pessimism. Implications of these findings
      for future research and for the support of families engaged in intensive home
      based behavioral intervention are discussed.

PMID- 11518486
TI  - Brief report: Recognition memory and stimulus-reward associations: indirect
      support for the role of ventromedial prefrontal dysfunction in autism.

PMID- 11518487
TI  - Brief report: Differential treatment outcomes for children with autistic spectrum
      disorder based on level of peer social avoidance.

PMID- 11518488
TI  - Brief report: Assessment of a screening tool for autistic spectrum disorders in
      adult population.

PMID- 11518489
TI  - Brief report: Children with autism as they grow up--description of adult
      inpatients with severe autism.

PMID- 11518490
TI  - What to measure in autism drug trials.

PMID- 11518491
TI  - What is the prevalence of Asperger disorder?

PMID- 11518492
TI  - Heat shock response and ageing: mechanisms and applications.
AB  - Ageing is associated with a decrease in the ability of cells to cope with
      environmental challenges. This is due partly to the attenuation of a primordial
      stress response, the so-called heat shock (HS) response, which induces the
      expression of heat shock proteins (HSPs), composed of chaperones and proteases.
      The attenuation of the HS response during ageing may be responsible for the
      accumulation of damaged proteins as well as abnormal regulation of cell death.
      Maintenance of the HS response by repeated mild heat stress causes anti-ageing
      hormetic effects on cells and organisms. Here, we describe the molecular
      mechanism and the state of the HS response as well as the role of specific HSPs
      during ageing, and discuss the possibility of hormetic modulation of ageing and
      longevity by repeated mild stress.

PMID- 11518493
TI  - Hormonal control of enzyme activity during the plasma membrane transformation of
      uterine epithelial cells.
AB  - Ultrastructural and light microscopic catalytic histochemical methods were used
      to study the distribution and changes in distribution of four phosphatase
      enzymes; alkaline phosphatase, 5'-nucleotidase, thiamine pyrophosphatase and
      adenosine triphosphatase in uterine epithelial cells in response to the ovarian
      hormones, oestrogen, progesterone or a combination of both used in different
      regimes on ovariectomised rats. Reaction product for all four enzymes was clearly
      localised in the epithelial cells, especially with oestrogen priming. However,
      the four enzymes showed markedly different patterns of organisation of reaction
      product in response to other hormonal treatments. Our findings clearly show that
      the expression of these enzymes is under ovarian hormonal control. However, while
      all of the enzymes are upregulated by oestrogen, the response to progesterone is
      variable, which can upregulate or downregulate different enzymes. The findings
      are particularly obvious at the electron microscopic level on the apical plasma
      membrane of the uterine epithelial cells, which was the main focus of our study.

PMID- 11518494
TI  - Patterns of expression of muscle-specific markers of differentiation in satellite
      cell cultures: determination by enzyme-linked immunoculture assay and confocal
      immunofluorescent assay.
AB  - Equine satellite cell clone SE-11 and ovine satellite cell clone I(1)were
      evaluated for expression of myosin heavy chain, myogenin, desmin, and muscle
      specific actin over a 240 h period in culture. An enzyme-linked immunoculture
      assay (ELICA) was capable of detecting these proteins at all time points
      evaluated. A linear relationship was demonstrated between the natural logarithm
      of the absorbance values (corrected for cell number) from the ELICA and percent
      fusion in both SE-11 and I(1)cultures. The r(2)values for SE-11 cultures were:
      desmin 0.82, muscle actin 0.81, myogenin 0.78, and myosin 0.70. The r(2)values
      for I(1)cultures were: desmin 0.77, muscle actin 0.72, myogenin 0.70, and myosin
      0.61. Our confocal results support the idea that differences exist between
      species in the differentiation dynamics of satellite cells. Further, these data
      suggest that the ELICA may be applied to previously conducted experiments,
      enabling additional data to be obtained with relation to muscle protein
      expression.

PMID- 11518495
TI  - Thyroid-stimulating hormone and growth hormone release alterations induced by
      mosquito larvae proteins on pituitary cells.
AB  - Mosquito larvae crude extract has shown to modulate cell proliferation of
      different mouse epithelial as well as human mononuclear cell populations in vivo
      and in vitro. A soluble fraction of the extract, with a molecular weight ranging
      from 12 to 80 kD, also showed an inhibitory effect on the proliferation of mouse
      hepatocytes. This effect disappeared after heating the extract at 90 degrees C
      for 60 min, suggesting that some proteinaceous molecule is involved. We report
      the effect of dialysed extract (MW >12 kD) on the concentration of both thyroid
      stimulating hormone (TSH) and growth hormone (GH) in an incubation medium of
      pituitary cells from normal and oestrogenised rats. Time- and dose-dependent
      response of both hormones resulted in increasing TSH levels. Concentrations of GH
      were lower in the treated than in control pituitary cells. The time elapsed until
      the finding of differences suggests the presence in the mosquito extract of some
      protein binding the hormone. The differences were not due to lethal toxic effects
      since the Trypan blue viability test showed no differences between control and
      treated cells. Furthermore, the effect disappeared when the extract had
      previously been heated at 90 degrees C for 60 min. Finally, our results suggest
      the presence of some proteins in the mosquito Culex pipiens L. larvae, which
      would act as a pituitary hormone regulator.

PMID- 11518496
TI  - IGF-I-induced apoptosis in LM2d6 cultured at a low concentration of fetal bovine
      serum.
AB  - We examined the effects of IGF-I (1-1000 ng/ml) on cell proliferation in LM2d6
      mouse fibroblast cells at 0.1, 1.0 and 5.0% fetal bovine serum (FBS). In medium
      containing 0.1% FBS, treatment of LM2d6 cells with IGF-I significantly reduced
      the cell number in a dose- and time-dependent manner, whereas no effects were
      seen at 1 or 5% FBS. Treatment of the cells with 0.1% FBS for 72 h caused DNA
      laddering and nuclear condensation. However, Scatchard analysis for IGF-I binding
      sites on the cells revealed that both the number and the affinity of IGF-I
      receptors were not greater than that of Balb/3T3 cells. Furthermore, the
      apoptotic action of Long (R(3))-IGF-I, an analogue of IGF-I that has a reduced
      affinity for IGF binding proteins, was not greater than that of IGF-I. Taken
      together, we conclude that IGF-I reduces cell proliferation at low levels of FBS
      due to the induction of apoptosis. This effect is probably not caused by an
      excess production of IGF binding proteins in LM2d6 cells.

PMID- 11518497
TI  - [Ca2+](i) rise in Jurkat E6-1 cell lines from different sources as a response to
      50 Hz magnetic field exposure as a reproducible effect and independent of poly-L
      lysine treatment.
AB  - Jurkat E6-1 cells obtained from three different sources were compared with
      respect to intracellular calcium response to a 50 Hz, 0.15 mT, magnetic field, to
      treatment with poly-L-lysine and to protein expression at the cell surface. The
      fura-2 single cell measurements were a replication study performed by three
      members of our group. The cells responded to the applied magnetic fields,
      although the percentage of responding cells was lower than in earlier studies.
      The geomagnetic field was backed off without changing the outcome of the
      intracellular calcium measurements. Fluorometric analyses showed no difference
      between the E6-1 cells obtained from three sources with respect to the expression
      of cell surface marker molecules. The addition of the cell adhesive peptide, poly
      L-lysine, did not itself cause any effects on the intracellular calcium
      concentration.

PMID- 11518498
TI  - Growth inhibition, morphological differentiation and stimulation of survival in
      neuronal cell type (Neuro-2a) treated with trophic molecules.
AB  - Trophic molecules are key regulators of survival, growth and differentiation of
      neural cells. Neuronal cell type Neuro-2a is a good model to study development
      and molecules modulating this process, and retinoic acid (RA) and neurotrophins
      (NGF, BDNF, NT-3 and NT-4) have been shown to be active in this modulation. The
      purpose of the present study was the functional analysis of these trophic
      molecules in our short-term bioassay of Neuro-2a cells, an immortalised murine
      neuroblastoma cell line. Through cell counting, image process and arithmetic
      combination of digital parameters of treated and untreated cultures, we show that
      RA inhibits growth and induces morphological neuronal phenotype of treated cells.
      Through DNA labelling with BrdU we also show that NGF, BDNF, and NT-3 increase
      survival and proliferation of cells, grown in serum-deprived media. From these
      results we conclude that neurotrophins have manifest trophic effects on cells
      improving survival, growth and proliferation and we also confirm the growth
      arrest and differentiation properties of RA on Neuro-2a cells.

PMID- 11518499
TI  - Impact of proliferative activity and tumorigenic conversion on mitochondrial
      function of fibroblasts in 2D and 3D culture.
AB  - The purpose of the present study was to examine mitochondrial function in
      differently transformed cells relative to their tumorigenic state and
      proliferative activity in vitro. An established two-step carcinogenesis model
      consisting of immortal and tumorigenic rat embryo fibroblasts that can be
      cultured as monolayers and multicellular spheroids was investigated. Flow
      cytometric measurements were carried out using the two mitochondrial-specific
      fluorochromes rhodamine 123 (Rh123) and 10-N-nonyl acridine orange (NAO), in
      combination with the DNA dye Hoechst 33342 for simultaneous cell cycle analysis.
      Since the accumulation of Rh123 depends on mitochondrial membrane potential,
      Rh123 fluorescence intensity gives an estimate of mitochondrial activity per
      cell, as determined by both overall mitochondrial function and mass. In contrast,
      NAO uptake reflects mitochondrial mass only, as it binds to cardiolipin in the
      inner mitochondrial membrane independently of membrane potential. Aliquots of
      cell suspensions derived from exponential monolayer, confluent monolayer, and a
      range of sizes of multicellular spheroids were stained with either Rh123 or NAO
      and Hoechst 33342, then mitochondrial mass and activity per unit cell volume and
      cellular DNA content were measured by flow cytometry. Differences in the average
      mitochondrial activity per cell in different cell lines and culture conditions
      were primarily due to alterations in cell volume. Importantly, tumorigenic
      conversion by ras-transfection did not consistently change mitochondrial activity
      per unit cell volume. The mitochondrial mass per unit cell volume increased for
      all cells when cellular quiescence was induced, either in monolayers or
      spheroids. However, mitochondrial function (activity/mass) decreased when cells
      became quiescent, resulting in a positive correlation between mitochondrial
      function and S-phase fraction, independent of transformation status or culture
      condition. We conclude that mitochondrial function reflects proliferative
      activity rather than tumorigenic conversion.

PMID- 11518500
TI  - Substrate-induced polarisation of cultured epitheliocytes and fibroblasts: non
      reactivity of Ras-transformed cells.
AB  - Non-transformed epitheliocytes and fibroblasts undergo modulations between the
      less polarised and more polarised phenotypes depending on the nature of the
      substrate. In contrast, transformed cells express polarised phenotype regardless
      of the substrate.

PMID- 11518501
TI  - Early posterior/ventral fate specification in the vertebrate embryo.
AB  - One of the central questions in developmental biology is that of how one cell can
      give rise to all specialized cell types and organs in the organism. Within the
      embryo, all tissues are composed of cells derived from one or more of the three
      germ layers, the ectoderm, the mesoderm, and the endoderm. Understanding the
      molecular events that underlie both the specification and patterning of the germ
      layers has been a long-standing interest for developmental biologists. Recent
      years have seen a rapid advancement in the elucidation of the molecular players
      implicated in patterning the vertebrate embryo. In this review, we will focus
      solely on the ventral and posterior fate acquisition in the ventral-lateral
      domains of the pregastrula embryo. We will address the embryonic origins of
      various tissues and will present embryological and experimental evidence to
      illustrate how "classically defined" ventral and posterior structures develop in
      all three germ layers. We will discuss the status of our current knowledge by
      focusing on the African frog Xenopus laevis, although we will also gather
      evidence from other vertebrates, where available. In particular, genetic studies
      in the zebrafish and mouse have been very informative in addressing the
      requirement for individual genes in these processes. The amphibian system has
      enjoyed great interest since the early days of experimental embryology, and
      constitutes the best understood system in terms of early patterning signals and
      axis specification. We want to draw interest to the embryological origins of
      cells that will develop into what we have collectively termed "posterior" and
      "ventral" cells/tissues, and we will address the involvement of the major
      signaling pathways implicated in posterior/ventral fate specification. Particular
      emphasis is given as to how these signaling pathways are integrated during early
      development for the specification of posterior and ventral fates.

PMID- 11518502
TI  - Fertilization blocks apoptosis of starfish eggs by inactivation of the MAP kinase
      pathway.
AB  - Fully grown starfish oocytes are arrested at prophase of meiosis I. The hormonal
      stimulation of 1-methyladenine (1-MA) induces meiosis reinitiation and germinal
      vesicle breakdown (GVBD). Optimal development occurs when maturing oocytes are
      fertilized between GVBD and first polar body emission. In the absence of sperm,
      oocytes complete both meiotic divisions to yield haploid interphase-arrested
      eggs. We now report that spontaneous and synchronous activation of caspase-3 in
      starfish eggs occurs 9-12 h after 1-MA stimulation. Then, caspase-dependent
      membrane blebbing and egg fragmentation occur, indicating that mature eggs
      undergo apoptosis if not fertilized. Activation of caspase-3 and induction of
      apoptosis are blocked both by a MEK inhibitor and by emetine treatment which
      inhibits MEK kinase (Mos) synthesis. Conversely, when recombinant GST-Mos is
      injected into the emetine-treated eggs, apoptosis is induced. These results
      indicate that persistent activation of the Mos/MEK/MAP kinase cascade gives the
      death-activating signal in starfish eggs. Fertilization inactivates the MAP
      kinase pathway and suppresses apoptosis, followed by normal development.

PMID- 11518503
TI  - Postmeiotic unfertilized starfish eggs die by apoptosis.
AB  - Fertilization of starfish eggs during meiosis results in rapid progression to
      embryogenesis as soon as meiosis II is completed. Unfertilized eggs complete
      meiosis and arrest in postmeiotic interphase for an, until now, indeterminate
      time. If they remain unfertilized, the mature postmeiotic eggs ultimately die.
      The aim of this study is to characterize the mechanism of death in postmeiotic
      unfertilized starfish eggs. We report that, in two species of starfish, in the
      absence of fertilization, postmeiotic interphase arrest persists for 16-20 h,
      after which time the cells synchronously and rapidly die. Dying eggs extrude
      membrane blebs, undergo cytoplasmic contraction and darkening, and fragment into
      vesicles in a manner reminiscent of apoptotic cells. The DNA of dying eggs is
      condensed, fragmented, and labeled by the TUNEL assay. Taken together, these data
      suggest that the default fate of postmeiotic starfish eggs, like their mammalian
      counterparts, is death by apoptosis. We further report that the onset and
      execution of apoptosis in this system is dependent on ongoing protein synthesis
      and is inhibited by a rise in intracellular Ca(2+), an essential component of the
      fertilization signaling pathway. We propose starfish eggs as a useful model to
      study developmentally regulated apoptosis.

PMID- 11518504
TI  - Elevated TGFbeta signaling inhibits ocular vascular development.
AB  - Alterations in the ocular vasculature are associated with retinal diseases such
      as retinopathy of prematurity and diabetic retinopathy. Vascular endothelial
      growth factor (VEGF) as a potent stimulator for normal and abnormal vascular
      growth has been extensively studied. However, little is known about secreted
      factors that negatively regulate vascular growth in ocular tissues. We now report
      that expression of a self-activating TGFbeta1 in the ocular lens of transgenic
      mice results in inhibition of retinal angiogenesis followed by retinal
      degeneration. Transgenic TGFbeta1 can rescue the hyperplasic hyaloid tissue and
      reverse the corneal deficiency in TGFbeta2-null embryos. These results
      demonstrate that TGFbeta signaling modulates development of ocular vasculature
      and cornea in a dosage-dependent manner and that TGFbeta1 can substitute for
      TGFbeta2 in ocular tissues.

PMID- 11518505
TI  - Salivary gland determination in Drosophila: a salivary-specific, fork head
      enhancer integrates spatial pattern and allows fork head autoregulation.
AB  - In the early Drosophila embryo, a system of coordinates is laid down by
      segmentation genes and dorsoventral patterning genes. Subsequently, these
      coordinates must be interpreted to define particular tissues and organs. To begin
      understanding this process for a single organ, we have studied how one of the
      first salivary gland genes, fork head (fkh), is turned on in the primordium of
      this organ, the salivary placode. A placode-specific fkh enhancer was identified
      10 kb from the coding sequence. Dissection of this enhancer showed that the
      apparently homogeneous placode is actually composed of at least four overlapping
      domains. These domains appear to be developmentally important because they
      predict the order of salivary invagination, are evolutionarily conserved, and are
      regulated by patterning genes that are important for salivary development. Three
      dorsoventral domains are defined by EGF receptor (EGFR) signaling, while stripes
      located at the anterior and posterior edges of the placode depend on wingless
      signaling. Further analysis identified sites in the enhancer that respond either
      positively to the primary activator of salivary gland genes, SEX COMBS REDUCED
      (SCR), or negatively to EGFR signaling. These results show that fkh integrates
      spatial pattern directly, without reference to other early salivary gland genes.
      In addition, we identified a binding site for FKH protein that appears to act in
      fkh autoregulation, keeping the gene active after SCR has disappeared from the
      placode. This autoregulation may explain how the salivary gland maintains its
      identity after the organ is established. Although the fkh enhancer integrates
      information needed to define the salivary placode, and although fkh mutants have
      the most extreme effects on salivary gland development thus far described, we
      argue that fkh is not a selector gene for salivary gland development and that
      there is no master, salivary gland selector gene. Instead, several genes
      independently sense spatial information and cooperate to define the salivary
      placode.

PMID- 11518506
TI  - Preoviposition activation of cathepsin-like proteinases in degenerating ovarian
      follicles of the mosquito Culex pipiens pallens.
AB  - Within developing ovaries of many insects, some developing follicles or oocytes
      usually degenerate (follicular atresia or oosorption), while the others may
      continue to grow to maturity, thus maintaining the balance between the number of
      eggs and reproductive circumstances such as available nutrients. To help clarify
      the phenomenon of follicular atresia during ovarian development, we examined
      cysteine proteinases stored in mosquito Culex pipiens pallens ovaries. First,
      analysis using synthesized substrates showed that cathepsin B- and L-like
      proteinases gradually accumulated in the developing ovaries after a blood meal,
      which required more than 10 min of preincubation under acidic conditions to reach
      their maximum activities. However, homogenates of degenerating follicles 3 days
      after feeding showed proteolytic activities without acid treatment, suggesting
      that the proteinases had already been activated, while the extract of normally
      developing follicles collected from the same ovaries required more than 10 min of
      acid preincubation to reach the optimum activities, suggesting that the enzymes
      remained as inactive forms. Chemical and immunohistochemical analyses showed that
      more proteinases are located in the cytoplasm, rather than being associated with
      yolk granules. Ovarian proteinases, which are believed to become activated at the
      onset of embryogenesis, should also be activated during oogenesis, presumably to
      enhance oosorption.

PMID- 11518507
TI  - Thoracic patterning by the Drosophila gap gene hunchback.
AB  - Localized gene expression patterns are critical for establishing body plans in
      all multicellular animals. In Drosophila, the gap gene hunchback (hb) is
      expressed in a dynamic pattern in anterior regions of the embryo. Hb protein is
      first detected as a shallow maternal gradient that prevents expression of
      posterior gap genes in anterior regions. hb mRNA is also expressed zygotically,
      first as a broad anterior domain controlled by the Bicoid (Bcd) morphogen, and
      then in a stripe at the position of parasegment 4 (PS4). Here, we show that the
      PS4-hb stripe changes the profile of the anterior Hb gradient by generating a
      localized peak of protein that persists until after the broad domain has started
      to decline. This peak is required specifically for the formation of the
      mesothoracic (T2) segment. At the molecular level, the PS4-hb stripe is critical
      for activation of the homeotic gene Antennapedia, but does not affect a gradient
      of Hb repressive activity formed by the combination of maternal and Bcd-dependent
      Hb. The repressive gradient is critical for establishing the positions of several
      target genes, including the gap genes Kruppel (Kr), knirps (kni), and giant (gt),
      and the homeotic gene Ultrabithorax (Ubx). Different Hb concentrations are
      sufficient for repression of gt, kni, and Ubx, but a very high level of Hb, or a
      combinatorial mechanism, is required for repression of Kr. These results suggest
      that the individual phases of hb transcription, which overlap temporally and
      spatially, contribute specific patterning functions in early embryogenesis.

PMID- 11518508
TI  - Stable anterior anchoring of the oocyte nucleus is required to establish
      dorsoventral polarity of the Drosophila egg.
AB  - In Drosophila, dorsoventral polarity is established by the asymmetric positioning
      of the oocyte nucleus. In egg chambers mutant for cap 'n' collar, the oocyte
      nucleus migrates correctly from a posterior to an anterior-dorsal position where
      it remains during stage 9 of oogenesis. However, at the end of stage 9, the
      nucleus leaves its anterior position and migrates towards the posterior pole. The
      mislocalisation of the nucleus is accompanied by changes in the microtubule
      network and a failure to maintain bicoid and oskar mRNAs at the anterior and
      posterior poles, respectively. gurken mRNA associates with the oocyte nucleus in
      cap 'n' collar mutants and initially the local secretion of Gurken protein
      activates the Drosophila EGF receptor in the overlying dorsal follicle cells.
      However, despite the presence of spatially correct Grk signalling during stage 9,
      eggs laid by cap 'n' collar females lack dorsoventral polarity. cap 'n' collar
      mutants, therefore, allow for the study of the influence of Grk signal duration
      on DV patterning in the follicular epithelium.

PMID- 11518509
TI  - NF-kappaB mediates FGF signal regulation of msx-1 expression.
AB  - The nuclear factor-kappaB (NF-kappaB) family of transcription factors is involved
      in proliferation, differentiation, and apoptosis in a stage- and cell-dependent
      manner. Recent evidence has shown that NF-kappaB activity is necessary for both
      chicken and mouse limb development. We report here that the NF-kappaB family
      member c-rel and the homeodomain gene msx-1 have partially overlapping expression
      patterns in the developing chick limb. In addition, inhibition of NF-kappaB
      activity resulted in a decrease in msx-1 mRNA expression. Sequence analysis of
      the msx-1 promoter revealed three potential kappaB-binding sites similar to the
      interferon-gamma (IFN-gamma) kappaB-binding site. These sites bound to c-Rel, as
      shown by electrophoretic mobility shift assay (EMSA). Furthermore, inhibition of
      NF-kappaB activity significantly reduced transactivation of the msx-1 promoter in
      response to FGF-2/-4, known stimulators of msx-1 expression. These results
      suggest that NF-kappaB mediates the FGF-2/-4 signal regulation of msx-1 gene
      expression.

PMID- 11518510
TI  - alpha11beta1 integrin is a receptor for interstitial collagens involved in cell
      migration and collagen reorganization on mesenchymal nonmuscle cells.
AB  - alpha11beta1 integrin constitutes a recent addition to the integrin family. Here,
      we present the first in vivo analysis of alpha11 protein and mRNA distribution
      during human embryonic development. alpha11 protein and mRNA were present in
      various mesenchymal cells around the cartilage anlage in the developing skeleton
      in a pattern similar to that described for the transcription factor scleraxis.
      alpha11 was also expressed by mesenchymal cells in intervertebral discs and in
      keratocytes in cornea, two sites with highly organized collagen networks. Neither
      alpha11 mRNA nor alpha11 protein could be detected in myogenic cells in human
      embryos. The described expression pattern is compatible with alpha11beta1
      functioning as a receptor for interstitial collagens in vivo. To test this
      hypothesis in vitro, full-length human alpha11 cDNA was stably transfected into
      the mouse satellite cell line C2C12, lacking endogenous collagen receptors.
      alpha11beta1 mediated cell adhesion to collagens I and IV (with a preference for
      collagen I) and formed focal contacts on collagens. In addition, alpha11beta1
      mediated contraction of fibrillar collagen gels in a manner similar to
      alpha2beta1, and supported migration on collagen I in response to chemotactic
      stimuli. Our data support a role for alpha11beta1 as a receptor for interstitial
      collagens on mesenchymally derived cells and suggest a multifunctional role of
      alpha11beta1 in the recognition and organization of interstitial collagen
      matrices during development.

PMID- 11518511
TI  - Hoxb2 and hoxb4 act together to specify ventral body wall formation.
AB  - Three different alleles of the Hoxb4 locus were generated by gene targeting in
      mice. Two alleles contain insertions of a selectable marker in the first exon in
      either orientation, and, in the third, the selectable marker was removed,
      resulting in premature termination of the protein. Presence and orientation of
      the selectable marker correlated with the severity of the phenotype, indicating
      that the selectable marker induces cis effects on neighboring genes that
      influence the phenotype. Homozygous mutants of all alleles had cervical skeletal
      defects similar to those previously reported for Hoxb4 mutant mice. In the most
      severe allele, Hoxb4(PolII), homozygous mutants died either in utero at
      approximately E15.5 or immediately after birth, with a severe defect in ventral
      body wall formation. Analysis of embryos showed thinning of the primary ventral
      body wall in mutants relative to control animals at E11.5, before secondary body
      wall formation. Prior to this defect, both Alx3 and Alx4 were specifically down
      regulated in the most ventral part of the primary body wall in Hoxb4(PolII)
      mutants. Hoxb4(loxp) mutants in which the neo gene has been removed did not have
      body wall or sternum defects. In contrast, both the Hoxb4(PolII) and the
      previously described Hoxb2(PolII) alleles that have body wall defects have been
      shown to disrupt the expression of both Hoxb2 and Hoxb4 in cell types that
      contribute to body wall formation. Our results are consistent with a model in
      which defects in ventral body wall formation require the simultaneous loss of at
      least Hoxb2 and Hoxb4, and may involve Alx3 and Alx4.

PMID- 11518512
TI  - Regulation of prostate branching morphogenesis by activin A and follistatin.
AB  - Ventral prostate development occurs by branching morphogenesis and is an androgen
      dependent process modulated by growth factors. Many growth factors have been
      implicated in branching morphogenesis including activins (dimers of beta(A) and
      beta(B) subunits); activin A inhibited branching of lung and kidney in vitro. Our
      aim was to examine the role of activins on prostatic development in vitro and
      their localization in vivo. Organ culture of day 0 rat ventral prostates for 6
      days with activin A (+/- testosterone) inhibited prostatic branching and growth
      without increasing apoptosis. The activin-binding protein follistatin increased
      branching in vitro in the absence (but not presence) of testosterone, suggesting
      endogenous activins may reduce prostatic branching morphogenesis. In vivo,
      inhibin alpha subunit was not expressed until puberty, therefore inhibins (dimers
      of alpha and beta subunits) are not involved in prostatic development. Activin
      beta(A) was immunolocalized to developing prostatic epithelium and mesenchymal
      aggregates at ductal tips. Activin beta(B) immunoreactivity was weak during
      development, but was upregulated in prostatic epithelium during puberty. Activin
      receptors were expressed throughout the prostatic epithelium. Follistatin mRNA
      and protein were expressed throughout the prostatic epithelium. The in vitro
      evidence that activin and follistatin have opposing effects on ductal branching
      suggests a role for activin as a negative regulator of prostatic ductal branching
      morphogenesis.

PMID- 11518513
TI  - VegT activation of Sox17 at the midblastula transition alters the response to
      nodal signals in the vegetal endoderm domain.
AB  - In Xenopus, the prospective endoderm and mesoderm are localized to discrete,
      adjacent domains at the beginning of gastrulation, and this is made evident by
      the expression of Sox17 in vegetal blastomeres and Brachyury (Xbra) in marginal
      blastomeres. Here, we examine the regulation of Sox17alpha expression and the
      role of Sox17alpha in establishing the vegetal endodermal gene expression domain.
      Injection of specific inhibitors of VegT or Nodal resulted in a loss of
      Sox17alpha expression in the gastrula. However, the onset of Sox17alpha
      expression at the midblastula transition was dependent on VegT, but not on Nodal
      function, indicating that Sox17alpha expression is initiated by VegT and then
      maintained by Nodal signals. Consistent with these results, VegT, but not Xenopus
      Nodal-related-1 (Xnr1), can activate Sox17alpha expression at the midblastula
      stage in animal explants. In addition, VegT activates Sox17alpha in the presence
      of cycloheximide or a Nodal antagonist, suggesting that Sox17alpha is an
      immediate-early target of VegT in vegetal blastomeres. Given that Nodal signals
      are necessary and sufficient for both mesodermal and endodermal gene expression,
      we propose that VegT activation of Sox17alpha at the midblastula transition
      prevents mesodermal gene expression in response to Nodal signals, thus
      establishing the vegetal endodermal gene expression domain. Supporting this idea,
      Sox17alpha misexpression in the marginal zone inhibits the expression of multiple
      mesodermal genes. Furthermore, in animal explants, Sox17alpha prevents the
      induction of Xbra and MyoD, but not Sox17beta or Mixer, in response to Xnr1.
      Therefore, VegT activation of Sox17alpha plays an important role in establishing
      a region of endoderm-specific gene expression in vegetal blastomeres.

PMID- 11518514
TI  - The SEL-12 presenilin mediates induction of the Caenorhabditis elegans uterine pi
      cell fate.
AB  - During Caenorhabditis elegans hermaphrodite development, the anchor cell induces
      the vulva and the uterine pi cells whose daughters connect to the vulva, thereby
      organizing the uterine-vulval connection. Both the initial selection of a single
      anchor cell during the anchor cell vs. ventral uterine precursor cell decision
      and the subsequent induction of the pi cell fate by the anchor cell are mediated
      by the lin-12 gene. Members of the presenilin gene family can cause early onset
      Alzheimer's disease when mutated and are also required for LIN-12/Notch signaling
      during development. We have shown that, in C. elegans, mutation of the sel-12
      encoded presenilin results in pi cell induction defects. By contrast, other lin
      12-mediated cell fate decisions occur normally in sel-12 mutants due to the
      redundant function of a second C. elegans presenilin called HOP-1. We found that
      the sel-12 egg-laying defect was partially rescued by expression of the sel-12
      gene in the pi cells. sel-12-mediated pi cell fate specification provides a
      useful system for the analysis of presenilin function at single cell resolution.

PMID- 11518515
TI  - The role of maternal axin in patterning the Xenopus embryo.
AB  - Regulation of the stability of beta catenin protein is a critical role of Wnt
      signaling cascades. In early Xenopus development, dorsal axis specification
      depends on regulation of beta catenin by both cytoplasmic and nuclear mechanisms.
      While the cytoplasmic protein axin is known as a key component of the cytoplasmic
      beta catenin degradation complex, loss-of-function studies are needed to
      establish whether it is required for dorso-ventral patterning in the embryo, and
      to test where in the embryo it carries out its function. Here, we show that
      embryos lacking maternal axin protein have increased levels of soluble beta
      catenin protein and increased nuclear localization of beta catenin in ventral
      nuclei at the blastula stage. These embryos gastrulate abnormally and develop
      with excessive notochord and head structures, and reduced tail and ventral
      components. They show increased expression of dorsal markers, including siamois,
      Xnr3, chordin, gsc, Xhex, and Otx2, decreased expression of Xwnt 8 and Xbra, and
      little alteration of BMP4 and Xvent1 and -2 mRNA levels. The ventral halves of
      axin-depleted embryos at the gastrula stage have dramatically increased levels of
      chordin expression, and severely decreased levels of Xwnt 8 mRNA expression,
      while BMP4 transcript levels are only slightly reduced. This dorso-anterior
      phenotype is rescued by axin mRNA injected into the vegetal pole of axin-depleted
      oocytes before fertilization. Interestingly, the phenotype was rescued by ventral
      but not dorsal injection of axin mRNA, at the 4-cell stage, although dorsal
      injection into wild-type embryos does cause ventralization. These results show
      directly that the localized ventral activity of maternal axin is critical for the
      correct patterning of the early Xenopus embryo.

PMID- 11518516
TI  - Involvement of heparin-binding EGF-like growth factor and its processing by
      metalloproteinases in early epithelial morphogenesis of the submandibular gland.
AB  - In the present study, the role of a member of the epidermal growth factor (EGF)
      family, heparin-binding EGF-like growth factor (HB-EGF), in organ development was
      investigated by using developing mouse submandibular gland (SMG), in which the
      EGF receptor signaling and heparan sulfate chains have been implicated. HB-EGF
      mRNA was detected in developing SMG by RT-PCR analysis and was expressed mainly
      in epithelium and weakly in mesenchyme of the embryonic SMG. Epithelial
      morphogenesis was inhibited by a synthetic peptide corresponding to the heparin
      binding domain of HB-EGF and by anti-HB-EGF neutralizing antibody. An in vitro
      assay using an EGF receptor ligand-dependent cell line, EP170.7 cells, allowed us
      to detect the growth factor activity in SMG-conditioned media, which was
      significantly reduced by anti-HB-EGF antibody. Furthermore, treatment of SMG
      rudiments with the hydroxamate-based metalloproteinase inhibitor OSU8-1, which
      inhibits processing of EGFR ligands including HB-EGF, markedly diminished the
      growth factor activity in conditioned media and resulted in almost complete
      inhibition of SMG morphogenesis. The inhibitory effects on morphogenesis were
      reversed, though partially, by adding the soluble form of HB-EGF. Our results
      provide the first evidence that HB-EGF is a crucial regulator of epithelial
      morphogenesis during organ development, highlighting the importance of its
      processing by metalloproteinases.

PMID- 11518517
TI  - Msx-2 and p21 mediate the pro-apoptotic but not the anti-proliferative effects of
      BMP4 on cultured sympathetic neuroblasts.
AB  - The differentiation, survival, and proliferation of developing sympathetic
      neuroblasts are all coordinately promoted by neurotrophins. In this study, we
      demonstrate that bone morphogenetic protein 4 (BMP4), a factor known to be
      necessary for the differentiation of sympathetic neurons (Schneider et al.,
      1999), conversely reduces both survival and proliferation of cultured E14
      sympathetic neuroblasts. The anti-proliferative effects of BMP4 occur more
      rapidly than the pro-apoptotic actions and appear to involve different
      intracellular mechanisms. BMP4 treatment induces expression of the transcription
      factor Msx-2 and the cyclin-dependent kinase inhibitor p21(CIP1/WAF1) (p21).
      Treatment of cells with oligonucleotides antisense to either of these genes
      prevents cell death after BMP4 treatment but does not significantly alter the
      anti-proliferative effects. Thus Msx-2 and p21 are necessary for BMP4-mediated
      cell death but not for promotion of exit from cell cycle. Although treatment of
      cultured E14 sympathetic neuroblasts with neurotrophins alone did not alter cell
      numbers, BMP4-induced cell death was prevented by co-treatment with either
      neurotrophin-3 (NT-3) or nerve growth factor (NGF). This suggests that BMP4 may
      also induce dependence of the cells on neurotrophins for survival. Thus,
      sympathetic neuron numbers may be determined in part by factors that inhibit the
      proliferation and survival of neuroblasts and make them dependent upon exogenous
      factors for survival.

PMID- 11518518
TI  - Alkalinization of acrosome measured by GFP as a pH indicator and its relation to
      sperm capacitation.
AB  - We previously targeted EGFP (a mutant of green fluorescent protein) to the lumen
      of the mouse sperm acrosome and reported the time course of EGFP release during
      the acrosome reaction. In the study reported here, we estimated the pH within the
      mouse sperm acrosome utilizing the pH-dependent nature of EGFP fluorescence. The
      average intra-acrosomal pH was estimated to be 5.3 +/- 0.1 immediately after
      sperm preparation, gradually increasing to 6.2 +/- 0.3 during 120 min of
      incubation in TYH media suitable for capacitation. Spontaneous acrosome reactions
      were noted to increase concomitantly with acrosomal alkalinization during
      incubation. We also demonstrated that acrosomal antigens detected by monoclonal
      antibodies MN7 and MC41 did not dissolve following the acrosome reaction in pH
      5.3 media, but dissolved at pH 6.2. These data suggest that acrosomal
      alkalinization during incubation conducive for sperm capacitation may function to
      alter acrosomal contents and prepare them for release during the acrosome
      reaction.

PMID- 11518519
TI  - Iron modulates the differentiation of a distinct population of glial precursor
      cells into oligodendrocytes.
AB  - Iron deficiency in children is associated with a number of neural defects
      including hypomyelination. It has been hypothesized by others that this
      hypomyelination is due to a failure in myelin production. Other possibilities
      include failure in the generation of oligodendrocytes from their precursor cells
      or an interruption in oligodendrocyte maturation. These hypotheses are based on
      the observations that there is a peak in brain iron uptake in vivo that coincides
      with the period of greatest myelination and that a shortage of iron leads to
      myelination deficiency. We now demonstrate that iron availability modulates the
      generation of oligodendrocytes from tripotential-glial restricted precursor (GRP)
      cells isolated from the embryonic day 13.5 rat spinal cord. In contrast, we found
      no effects of iron on oligodendrocyte maturation or survival in vitro, nor did we
      find that increasing iron availability above basal levels increases
      oligodendrocyte generation from bipotential oligodendrocyte-type-2
      astrocyte/oligodendrocyte precursor cells (O-2A/OPCs). Our results raise the
      possibility that iron may affect oligodendrocyte development at stages during
      early embryogenesis rather than during later development.

PMID- 11518520
TI  - Four-body potentials reveal protein-specific correlations to stability changes
      caused by hydrophobic core mutations.
AB  - Mutational experiments show how changes in the hydrophobic cores of proteins
      affect their stabilities. Here, we estimate these effects computationally, using
      four-body likelihood potentials obtained by simplicial neighborhood analysis of
      protein packing (SNAPP). In this procedure, the volume of a known protein
      structure is tiled with tetrahedra having the center of mass of one amino acid
      side-chain at each vertex. Log-likelihoods are computed for the 8855 possible
      tetrahedra with equivalent compositions from structural databases and amino acid
      frequencies. The sum of these four-body potentials for tetrahedra present in a
      given protein yields the SNAPP score. Mutations change this sum by changing the
      compositions of tetrahedra containing the mutated residue and their related
      potentials. Linear correlation coefficients between experimental mutational
      stability changes, Delta(DeltaG(unfold)), and those based on SNAPP scoring range
      from 0.70 to 0.94 for hydrophobic core mutations in five different proteins.
      Accurate predictions for the effects of hydrophobic core mutations can therefore
      be obtained by virtual mutagenesis, based on changes to the total SNAPP
      likelihood potential. Significantly, slopes of the relation between
      Delta(DeltaG(unfold)) and DeltaSNAPP for different proteins are statistically
      distinct, and we show that these protein-specific effects can be estimated using
      the average SNAPP score per residue, which is readily derived from the analysis
      itself. This result enhances the predictive value of statistical potentials and
      supports previous suggestions that "comparable" mutations in different proteins
      may lead to different Delta(DeltaG(unfold)) values because of differences in
      their flexibility and/or conformational entropy.

PMID- 11518521
TI  - SNAPping up functionally related genes based on context information: a
      colinearity-free approach.
AB  - We describe a computational approach for finding genes that are functionally
      related but do not possess any noticeable sequence similarity. Our method, which
      we call SNAP (similarity-neighborhood approach), reveals the conservation of gene
      order on bacterial chromosomes based on both cross-genome comparison and context
      information. The novel feature of this method is that it does not rely on
      detection of conserved colinear gene strings. Instead, we introduce the notion of
      a similarity-neighborhood graph (SN-graph), which is constructed from the chains
      of similarity and neighborhood relationships between orthologous genes in
      different genomes and adjacent genes in the same genome, respectively. An SN
      cycle is defined as a closed path on the SN-graph and is postulated to
      preferentially join functionally related gene products that participate in the
      same biochemical or regulatory process. We demonstrate the substantial non
      randomness and functional significance of SN-cycles derived from real genome data
      and estimate the prediction accuracy of SNAP in assigning broad function to
      uncharacterized proteins. Examples of practical application of SNAP for improving
      the quality of genome annotation are described.

PMID- 11518522
TI  - Nucleotide sequence of coliphage HK620 and the evolution of lambdoid phages.
AB  - HK620 is a temperate lambdoid bacteriophage that adsorbs to the O-antigen of its
      host, Escherichia coli H. The genome of a temperature-sensitive clear-plaque
      mutant consists of 38,297 nucleotides in which we recognize 60 open reading
      frames (orfs). Eighteen of these lie in a region of the genome that we call the
      virion structure domain. The other 42 orfs lie in what we call the metabolic
      domain. Virions of HK620 resemble those of phage P22. The virion structural orfs
      encode three kinds of putative proteins relative to the virion proteins of P22:
      (1) those that are nearly (about 90 %) identical; (2) those that are weakly
      (about 30 %) identical; and (3) those composed of nearly and weakly identical
      segments. We hypothesize that these composite proteins form bridges between the
      virion proteins of the other two kinds. Three of the putative virion proteins
      that are only weakly identical to P22 proteins are 71, 60 and 79 % identical to
      proteins encoded by the phage APSE-1, whose virions also resemble those of P22.
      Because the hosts of APSE-1 and HK620 have been separated from each other by an
      estimated 200 My, we propose using the amino acid differences that have
      accumulated in these proteins to estimate a biological clock for temperate
      lambdoid phages. The putative transcriptional regulatory gene circuitry of HK620
      seems to resemble that of phage lambda. Integration, on the other hand, resembles
      that of satellite phage P4 in that the attP sequence lies between the leftward
      promoter and int rather than downstream of int. Comparing the metabolic domains
      of several lambdoid phage genomes reveals seven short conserved sequences roughly
      defining boundaries of functional modules. We propose that these boundary
      sequences are foci of genetic recombination that serve to assort the modules and
      make the metabolic domain highly mosaic genetically.

PMID- 11518523
TI  - Correlated sequence-signatures as markers of protein-protein interaction.
AB  - As protein-protein interaction is intrinsic to most cellular processes, the
      ability to predict which proteins in the cell interact can aid significantly in
      identifying the function of newly discovered proteins, and in understanding the
      molecular networks they participate in. Here we demonstrate that characteristic
      pairs of sequence-signatures can be learned from a database of experimentally
      determined interacting proteins, where one protein contains the one sequence
      signature and its interacting partner contains the other sequence-signature. The
      sequence-signatures that recur in concert in various pairs of interacting
      proteins are termed correlated sequence-signatures, and it is proposed that they
      can be used for predicting putative pairs of interacting partners in the cell. We
      demonstrate the potential of this approach on a comprehensive database of
      experimentally determined pairs of interacting proteins in the yeast
      Saccharomyces cerevisiae. The proteins in this database have been characterized
      by their sequence-signatures, as defined by the InterPro classification. A
      statistical analysis performed on all possible combinations of sequence-signature
      pairs has identified those pairs that are over-represented in the database of
      yeast interacting proteins. It is demonstrated how the use of the correlated
      sequence-signatures as identifiers of interacting proteins can reduce
      significantly the search space, and enable directed experimental interaction
      screens.

PMID- 11518524
TI  - The evolution and structural anatomy of the small molecule metabolic pathways in
      Escherichia coli.
AB  - The 106 small molecule metabolic (SMM) pathways in Escherichia coli are formed by
      the protein products of 581 genes. We can define 722 domains, nearly all of which
      are homologous to proteins of known structure, that form all or part of 510 of
      these proteins. This information allows us to answer general questions on the
      structural anatomy of the SMM pathway proteins and to trace family relationships
      and recruitment events within and across pathways. Half the gene products contain
      a single domain and half are formed by combinations of between two and six
      domains. The 722 domains belong to one of 213 families that have between one and
      51 members. Family members usually conserve their catalytic or cofactor binding
      properties; substrate recognition is rarely conserved. Of the 213 families,
      members of only a quarter occur in isolation, i.e. they form single-domain
      proteins. Most members of the other families combine with domains from just one
      or two other families and a few more versatile families can combine with several
      different partners. Excluding isoenzymes, more than twice as many homologues are
      distributed across pathways as within pathways. However, serial recruitment, with
      two consecutive enzymes both being recruited to another pathway, is rare and
      recruitment of three consecutive enzymes is not observed. Only eight of the 106
      pathways have a high number of homologues. Homology between consecutive pairs of
      enzymes with conservation of the main substrate-binding site but change in
      catalytic mechanism (which would support a simple model of retrograde pathway
      evolution) occurs only six times in the whole set of enzymes. Most of the domains
      that form SMM pathways have homologues in non-SMM pathways. Taken together, these
      results imply a pervasive "mosaic" model for the formation of protein repertoires
      and pathways.

PMID- 11518525
TI  - Peptide mimics of SNARE transmembrane segments drive membrane fusion depending on
      their conformational plasticity.
AB  - SNARE proteins are essential for different types of intracellular membrane
      fusion. Whereas interaction between their cytoplasmic domains is held responsible
      for establishing membrane proximity, the role of the transmembrane segments in
      the fusion process is currently not clear. Here, we used an in vitro approach
      based on lipid mixing and electron microscopy to examine a potential fusogenic
      activity of the transmembrane segments. We show that the presence of synthetic
      peptides representing the transmembrane segments of the presynaptic soluble N
      ethylmaleimide-sensitive factor attachment protein receptors (SNAREs)
      synaptobrevin II (also referred to as VAMP II) or syntaxin 1A, but not of an
      unrelated control peptide, in liposomal membranes drives their fusion. Liposome
      aggregation by millimolar Ca(2+) concentrations strongly potentiated the effect
      of the peptides; this indicates that juxtaposition of the bilayers favours their
      fusion in the absence of the cytoplasmic SNARE domains. Peptide-driven fusion is
      reminiscent of natural membrane fusion, since it was suppressed by lysolipid and
      involved both bilayer leaflets. This suggests transient presence of a hemifusion
      intermediate followed by complete membrane merger. Structural studies of the
      peptides in lipid bilayers performed by Fourier transform infrared spectroscopy
      indicated mixtures of alpha-helical and beta-sheet conformations. In isotropic
      solution, circular dichroism spectroscopy showed the peptides to exist in a
      concentration-dependent equilibrium of alpha-helical and beta-sheet structures.
      Interestingly, the fusogenic activity decreased with increasing stability of the
      alpha-helical solution structure for a panel of variant peptides. Thus,
      structural plasticity of transmembrane segments may be important for SNARE
      protein function at a late step in membrane fusion.

PMID- 11518526
TI  - Cholesterol, a modulator of membrane-associated Abeta-fibrillogenesis and
      neurotoxicity.
AB  - Recent studies have suggested that cholesterol, an important determinant of the
      physical state of biological membranes, plays a significant role in the
      development of Alzheimer's disease. We have employed in situ scanning probe
      microscopy, fluorescence anisotropy, and electron microscopy to investigate how
      cholesterol levels within total brain lipid bilayers effect amyloid beta-peptide
      (Abeta)-assembly. Fluorescence anisotropy measurements revealed that the relative
      fluidity of the total brain lipid membranes was influenced by the level of
      cholesterol and the addition of Abeta40 resulted in a decrease in the overall
      vesicle fluidity. In situ scanning probe microscopy performed on supported planar
      bilayers of total brain lipid revealed a correlation between membrane fluidity,
      as influenced by cholesterol level, and the extent of Abeta-insertion and
      subsequent fibrillogenesis. These observations were consistent with fluorescence
      microscopy studies of PC-12 and SH-SY5Y cell lines exposed to exogenous Abeta,
      which revealed an inverse correlation between membrane cholesterol level, and
      Abeta-cell surface binding and subsequent cell death. These results collectively
      suggest that Abeta-cell surface interactions are mediated by cellular cholesterol
      levels, the distribution of cholesterol throughout the cell, and membrane
      fluidity.

PMID- 11518527
TI  - Structure and characterization of AgfB from Salmonella enteritidis thin
      aggregative fimbriae.
AB  - The agfBAC operon of Salmonella enteritidis encodes thin aggregative fimbriae,
      fibrous, polymeric structures primarily composed of AgfA fimbrins. Although
      uncharacterized, AgfB shows a 51 % overall amino acid sequence similarity to
      AgfA. Using AgfB epitope-specific antiserum, AgfB was detected as a minor
      component of whole, purified fimbriae. Like AgfA, AgfB was released from purified
      fimbriae by >70 % formic acid, whereupon both AgfA-AgfA and AgfA-AgfB dimers as
      well as monomers were detected. This suggested that AgfB may form specific,
      highly stable, structural associations with AgfA in native fimbrial filaments,
      associations that were weakened in structurally unstable fibers derived from AgfA
      chimeric fimbrial mutants. Detailed sequence comparisons between AgfA and AgfB
      showed that AgfB harbored a similar fivefold repeated sequence pattern
      (x(6)QxGx(2)NxAx(3)Q), and contained structural motifs similar to the parallel
      beta helix model proposed for AgfA. Molecular modeling of AgfB revealed a 3D
      structure remarkably similar to that of AgfA, the structures differing
      principally in the surface disposition of non-conserved, basic, acidic and non
      polar residues. Thus AgfB is a fimbrin-like structural homologue of AgfA and an
      integral, minor component of native thin aggregative fimbrial fibers. AgfB from
      an agfA deletion strain was detected as a non-fimbrial, SDS-insoluble form in the
      supernatant and was purified. AgfA from an agfB deletion strain was found in both
      SDS-soluble and insoluble, non-fimbrial forms. No AgfA-AgfA dimers were detected
      in the absence of AgfB. Fimbriae formation by intercellular complementation
      between agfB and agfA deletion strains could not be shown under a variety of
      conditions, indicating that AgfA and AgfB are not freely diffusible in S.
      enteritidis. This has important implications on the current assembly hypothesis
      for thin aggregative fimbriae.

PMID- 11518528
TI  - Crystal structure of human peroxiredoxin 5, a novel type of mammalian
      peroxiredoxin at 1.5 A resolution.
AB  - The peroxiredoxins define an emerging family of peroxidases able to reduce
      hydrogen peroxide and alkyl hydroperoxides with the use of reducing equivalents
      derived from thiol-containing donor molecules such as thioredoxin, glutathione,
      trypanothione and AhpF. Peroxiredoxins have been identified in prokaryotes as
      well as in eukaryotes. Peroxiredoxin 5 (PRDX5) is a novel type of mammalian
      thioredoxin peroxidase widely expressed in tissues and located cellularly to
      mitochondria, peroxisomes and cytosol. Functionally, PRDX5 has been implicated in
      antioxidant protective mechanisms as well as in signal transduction in cells. We
      report here the 1.5 A resolution crystal structure of human PRDX5 in its reduced
      form. The crystal structure reveals that PRDX5 presents a thioredoxin-like
      domain. Interestingly, the crystal structure shows also that PRDX5 does not form
      a dimer like other mammalian members of the peroxiredoxin family. In the reduced
      form of PRDX5, Cys47 and Cys151 are distant of 13.8 A although these two cysteine
      residues are thought to be involved in peroxide reductase activity by forming an
      intramolecular disulfide intermediate in the oxidized enzyme. These data suggest
      that the enzyme would necessitate a conformational change to form a disulfide
      bond between catalytic Cys47 and Cys151 upon oxidation according to proposed
      peroxide reduction mechanisms. Moreover, the presence of a benzoate ion, a
      hydroxyl radical scavenger, was noted close to the active-site pocket. The
      possible role of benzoate in the antioxidant activity of PRDX5 is discussed.

PMID- 11518529
TI  - Crystal structure of histidinol phosphate aminotransferase (HisC) from
      Escherichia coli, and its covalent complex with pyridoxal-5'-phosphate and l
      histidinol phosphate.
AB  - The biosynthesis of histidine is a central metabolic process in organisms ranging
      from bacteria to yeast and plants. The seventh step in the synthesis of histidine
      within eubacteria is carried out by a pyridoxal-5'-phosphate (PLP)-dependent l
      histidinol phosphate aminotransferase (HisC, EC 2.6.1.9). Here, we report the
      crystal structure of l-histidinol phosphate aminotransferase from Escherichia
      coli, as a complex with pyridoxamine-5'-phosphate (PMP) at 1.5 A resolution, as
      the internal aldimine with PLP, and in a covalent, tetrahedral complex consisting
      of PLP and l-histidinol phosphate attached to Lys214, both at 2.2 A resolution.
      This covalent complex resembles, in structural terms, the gem-diamine
      intermediate that is formed transiently during conversion of the internal to
      external aldimine.HisC is a dimeric enzyme with a mass of approximately 80 kDa.
      Like most PLP-dependent enzymes, each HisC monomer consists of two domains, a
      larger PLP-binding domain having an alpha/beta/alpha topology, and a smaller
      domain. An N-terminal arm contributes to the dimerization of the two monomers.
      The PLP-binding domain of HisC shows weak sequence similarity, but significant
      structural similarity with the PLP-binding domains of a number of PLP-dependent
      enzymes. Residues that interact with the PLP cofactor, including Tyr55, Asn157,
      Asp184, Tyr187, Ser213, Lys214 and Arg222, are conserved in the family of
      aspartate, tyrosine and histidinol phosphate aminotransferases. The imidazole
      ring of l-histidinol phosphate is bound, in part, through a hydrogen bond with
      Tyr110, a residue that is substituted by Phe in the broad substrate specific HisC
      enzymes from Zymomonas mobilis and Bacillus subtilis. Comparison of the
      structures of the HisC internal aldimine, the PMP complex and the HisC l
      histidinol phosphate complex reveal minimal changes in protein or ligand
      structure. Proton transfer, required for conversion of the gem-diamine to the
      external aldimine, does not appear to be limited by the distance between
      substrate and lysine amino groups. We propose that the tetrahedral complex has
      resulted from non-productive binding of l-histidinol phosphate soaked into the
      HisC crystals, resulting in its inability to be converted to the external
      aldimine at the HisC active site.

PMID- 11518530
TI  - Localization of L11 protein on the ribosome and elucidation of its involvement in
      EF-G-dependent translocation.
AB  - L11 protein is located at the base of the L7/L12 stalk of the 50 S subunit of the
      Escherichia coli ribosome. Because of the flexible nature of the region, recent X
      ray crystallographic studies of the 50 S subunit failed to locate the N-terminal
      domain of the protein. We have determined the position of the complete L11
      protein by comparing a three-dimensional cryo-EM reconstruction of the 70 S
      ribosome, isolated from a mutant lacking ribosomal protein L11, with the three
      dimensional map of the wild-type ribosome. Fitting of the X-ray coordinates of
      L11-23 S RNA complex and EF-G into the cryo-EM maps combined with molecular
      modeling, reveals that, following EF-G-dependent GTP hydrolysis, domain V of EF-G
      intrudes into the cleft between the 23 S ribosomal RNA and the N-terminal domain
      of L11 (where the antibiotic thiostrepton binds), causing the N-terminal domain
      to move and thereby inducing the formation of the arc-like connection with the G'
      domain of EF-G. The results provide a new insight into the mechanism of EF-G
      dependent translocation.

PMID- 11518531
TI  - Crystal structures of cystathionine gamma-synthase inhibitor complexes
      rationalize the increased affinity of a novel inhibitor.
AB  - Cystathionine gamma-synthase catalyzes the committed step of methionine
      biosynthesis. This pathway is unique to microorganisms and plants, rendering the
      enzyme an attractive target for the development of antimicrobials and herbicides.
      We solved the crystal structures of complexes of cystathionine gamma-synthase
      (CGS) from Nicotiana tabacum with inhibitors of different compound classes. The
      complex with the substrate analog dl-E-2-amino-5-phosphono-3-pentenoic acid
      verifies the carboxylate-binding function of Arg423 and identifies the phosphate
      binding pocket of the active site. The structure shows the function of Lys165 in
      specificity determination and suggests a role for the flexible side-chain of
      Tyr163 in catalysis. The importance of hydrophobic interactions for binding to
      the active-site center is highlighted by the complex with 3
      (phosphonomethyl)pyridine-2-carboxylic acid. The low affinity of this compound is
      due to the non-optimal arrangement of the functional groups binding to the
      phosphate and carboxylate-recognition site, respectively. The newly identified
      inhibitor 5-carboxymethylthio-3-(3'-chlorophenyl)-1,2,4-oxadiazol, in contrast,
      shows the highest affinity to CGS reported so far. This affinity is due to
      binding to an additional active-site pocket not used by the physiological
      substrates. The inhibitor binds to the carboxylate-recognition site, and its
      tightly bent conformation enables it to occupy the novel binding pocket between
      Arg423 and Ser388. The described structures suggest improvements for known
      inhibitors and give guidelines for the development of new lead compounds.

PMID- 11518532
TI  - Analysis of rapid, large-scale protein quaternary structural changes: time
      resolved X-ray solution scattering of Nudaurelia capensis omega virus (NomegaV)
      maturation.
AB  - Time-resolved small-angle X-ray scattering (TR-SAXS) was used to study the
      kinetics of a large conformational change that occurs during the maturation of an
      icosahedral virus. Virus-like particles (VLPs) of the T=4 non-enveloped RNA virus
      Nudaurelia capensis omega virus (NomegaV) were shown to undergo a large pH
      dependent conformational change. Electron cryo-microscopy (cryoEM) and X-ray
      solution scattering were used to show that the precursor VLP (procapsid) was 16 %
      larger in diameter than the resulting capsid, which was shown by the cryoEM study
      to closely resemble the infectious mature virion. The procapsid form of the VLPs
      was observed at pH 7.5 and was converted to the capsid form at pH 5.0. Static
      SAXS measurements of the VLPs in solutions ranging between these pH values
      determined that the half-titration point of the transition was pH 6.0. Time
      resolved SAXS experiments were performed on VLP solutions by initiating a pH
      change from 7.5 to 5.0 using a stopped-flow device, and the time-scale of the
      conformational change occurred in the subsecond range. Using a less drastic pH
      change (lowering the pH to 5.8 or 5.5), the conformational change occurred more
      slowly, on the subminute or minute time-scale, with the detection of a fast
      forming intermediate in the transition. Further characterization using static
      SAXS measurements showed that the conformational change was initially reversible
      but became irreversible after autoproteolytic maturation was about 15 % complete.
      In addition to characterizing the large quaternary conformational change, we have
      been able for the first time to demonstrate that it takes place on the subsecond
      time-scale, a regime comparable to that observed in other multisubunit
      assemblies.

PMID- 11518533
TI  - Mechanisms for ligand binding to GluR0 ion channels: crystal structures of the
      glutamate and serine complexes and a closed apo state.
AB  - High-resolution structures of the ligand binding core of GluR0, a glutamate
      receptor ion channel from Synechocystis PCC 6803, have been solved by X-ray
      diffraction. The GluR0 structures reveal homology with bacterial periplasmic
      binding proteins and the rat GluR2 AMPA subtype neurotransmitter receptor. The
      ligand binding site is formed by a cleft between two globular alpha/beta domains.
      L-Glutamate binds in an extended conformation, similar to that observed for
      glutamine binding protein (GlnBP). However, the L-glutamate gamma-carboxyl group
      interacts exclusively with Asn51 in domain 1, different from the interactions of
      ligand with domain 2 residues observed for GluR2 and GlnBP. To address how
      neutral amino acids activate GluR0 gating we solved the structure of the binding
      site complex with L-serine. This revealed solvent molecules acting as surrogate
      ligand atoms, such that the serine OH group makes solvent-mediated hydrogen bonds
      with Asn51. The structure of a ligand-free, closed-cleft conformation revealed an
      extensive hydrogen bond network mediated by solvent molecules. Equilibrium
      centrifugation analysis revealed dimerization of the GluR0 ligand binding core
      with a dissociation constant of 0.8 microM. In the crystal, a symmetrical dimer
      involving residues in domain 1 occurs along a crystallographic 2-fold axis and
      suggests that tetrameric glutamate receptor ion channels are assembled from
      dimers of dimers. We propose that ligand-induced conformational changes cause the
      ion channel to open as a result of an increase in domain 2 separation relative to
      the dimer interface.

PMID- 11518534
TI  - Structure of the C2 domain from novel protein kinase Cepsilon. A membrane binding
      model for Ca(2+)-independent C2 domains.
AB  - Protein kinase Cepsilon (PKCepsilon) is a member of the novel PKCs which are
      activated by acidic phospholipids, diacylglycerol and phorbol esters, but lack
      the calcium dependence of classical PKC isotypes. The crystal structures of the
      C2 domain of PKCepsilon, crystallized both in the absence and in the presence of
      the two acidic phospholipids, 1,2-dicaproyl-sn-phosphatidyl-l-serine (DCPS) and
      1,2-dicaproyl-sn-phosphatidic acid (DCPA), have now been determined at 2.1, 1.7
      and 2.8 A resolution, respectively. The central feature of the PKCepsilon-C2
      domain structure is an eight-stranded, antiparallel, beta-sandwich with a type II
      topology similar to that of the C2 domains from phospholipase C and from novel
      PKCdelta. Despite the similar topology, important differences are found between
      the structures of C2 domains from PKCs delta and epsilon, suggesting they be
      considered as different PKC subclasses. Site-directed mutagenesis experiments and
      structural changes in the PKCepsilon-C2 domain from crystals with DCPS or DCPA
      indicate, though phospholipids were not visible in these structures, that loops
      joining strands beta1-beta2 and beta5-beta6 participate in the binding to anionic
      membranes. The different behavior in membrane-binding and activation between
      PKCepsilon and classical PKCs appears to originate in localized structural
      changes, which include a major reorganization of the region corresponding to the
      calcium binding pocket in classical PKCs. A mechanism is proposed for the
      interaction of the PKCepsilon-C2 domain with model membranes that retains basic
      features of the docking of C2 domains from classical, calcium-dependent, PKCs.

PMID- 11518535
TI  - Reversible lattice repacking illustrates the temperature dependence of
      macromolecular interactions.
AB  - Flash-freezing, which has become routine in macromolecular X-ray crystallography,
      causes the crystal to contract substantially. In the case of Escherichia coli
      beta-galactosidase the changes are reversible and are shown to be due to lattice
      repacking. On cooling, the area of the protein surface involved in lattice
      contacts increases by 50 %. There are substantial alterations in intermolecular
      contacts, these changes being dominated by the long, polar side-chains. For
      entropic reasons such side-chains, as well as surface solvent molecules, tend to
      be somewhat disordered at room temperature but can form extensive hydrogen-bonded
      networks on cooling. Low-temperature density measurements suggest that, at least
      in some cases, the beneficial effect of cryosolvents may be due to a density
      increase on vitrification which reduces the volume of bulk solvent that needs to
      be expelled from the crystal. Analysis of beta-galactosidase and several other
      proteins suggests that both intramolecular and intermolecular contact interfaces
      can be perturbed by cryocooling but that the changes tend to be more dramatic in
      the latter case. The temperature-dependence of the intermolecular interactions
      suggests that caution may be necessary in interpreting protein-protein and
      protein-nucleic acid interactions based on low-temperature crystal structures.

PMID- 11518536
TI  - The X-ray structure of Aspergillus aculeatus polygalacturonase and a modeled
      structure of the polygalacturonase-octagalacturonate complex.
AB  - Polygalacturonases hydrolyze the alpha-(1-4) glycosidic bonds of de-esterified
      pectate in the smooth region of the plant cell wall. Crystal structures of
      polygalacturonase from Aspergillus aculeatus were determined at pH 4.5 and 8.5
      both to 2.0 A resolution. A. aculeatus polygalacturonase is a glycoprotein with
      one N and ten O-glycosylation sites and folds into a right-handed parallel beta
      helix. The structures of the three independent molecules are essentially the
      same, showing no dependency on pH or crystal packing, and are very similar to
      that of Aspergillus niger polygalacturonase. However, the structures of the long
      T1 loop containing a catalytic tyrosine residue are significantly different in
      the two proteins. A three-dimensional model showing the substrate binding mode
      for a family 28 hydrolase was obtained by a combined approach of flexible
      docking, molecular dynamics simulations, and energy minimization. The
      octagalacturonate substrate was modeled as an unbent irregular helix with the -1
      ring in a half-chair ((4)H(3)) form that approaches the transition state
      conformation. A comparative modeling of the three polygalacturonases with known
      structure shows that six subsites ranging from -4 to +2 are clearly defined but
      subsites -5 and +3 may or may not be shaped depending on the nearby amino acid
      residues. Both distal subsites are mostly exposed to the solvent region and have
      weak binding affinity even if they exist. The complex model provides a clear
      explanation for the functions, either in catalysis or in substrate binding, of
      all conserved amino acid residues in the polygalacturonase family of proteins.
      Modeling suggests that the role of the conserved Asn157 and Tyr270, which had
      previously been unidentified, may be in transition state stabilization. In A.
      niger polygalacturonase, the long T1 loop may have to undergo conformational
      change upon binding of the substrate to bring the tyrosine residue close to
      subsite -1.

PMID- 11518537
TI  - Prediction of folding mechanism for circular-permuted proteins.
AB  - Recent theoretical and experimental studies have suggested that real proteins
      have sequences with sufficiently small energetic frustration that topological
      effects are central in determining the folding mechanism. A particularly
      interesting and challenging framework for exploring and testing the viability of
      these energetically unfrustrated models is the study of circular-permuted
      proteins. Here we present the results of the application of a topology-based
      model to the study of circular permuted SH3 and CI2, in comparison with the
      available experimental results. The folding mechanism of the permuted proteins
      emerging from our simulations is in very good agreement with the experimental
      observations. The differences between the folding mechanisms of the permuted and
      wild-type proteins seem then to be strongly related to the change in the native
      state topology.

PMID- 11518538
TI  - Helix-helix packing and interfacial pairwise interactions of residues in membrane
      proteins.
AB  - Helix-helix packing plays a critical role in maintaining the tertiary structures
      of helical membrane proteins. By examining the overall distribution of voids and
      pockets in the transmembrane (TM) regions of helical membrane proteins, we found
      that bacteriorhodopsin and halorhodopsin are the most tightly packed, whereas
      mechanosensitive channel is the least tightly packed. Large residues F, W, and H
      have the highest propensity to be in a TM void or a pocket, whereas small
      residues such as S, G, A, and T are least likely to be found in a void or a
      pocket. The coordination number for non-bonded interactions for each of the
      residue types is found to correlate with the size of the residue. To assess
      specific interhelical interactions between residues, we have developed a new
      computational method to characterize nearest neighboring atoms that are in
      physical contact. Using an atom-based probabilistic model, we estimate the
      membrane helical interfacial pairwise (MHIP) propensity. We found that there are
      many residue pairs that have high propensity for interhelical interactions, but
      disulfide bonds are rarely found in the TM regions. The high propensity pairs
      include residue pairs between an aromatic residue and a basic residue (W-R, W-H,
      and Y-K). In addition, many residue pairs have high propensity to form
      interhelical polar-polar atomic contacts, for example, residue pairs between two
      ionizable residues, between one ionizable residue and one N or Q. Soluble
      proteins do not share this pattern of diverse polar-polar interhelical
      interaction. Exploratory analysis by clustering of the MHIP values suggests that
      residues similar in side-chain branchness, cyclic structures, and size tend to
      have correlated behavior in participating interhelical interactions. A chi-square
      test rejects the null hypothesis that membrane protein and soluble protein have
      the same distribution of interhelical pairwise propensity. This observation may
      help us to understand the folding mechanism of membrane proteins.

PMID- 11518539
TI  - Probing subtle differences in the hydrogen exchange behavior of variants of the
      human alpha-lactalbumin molten globule using mass spectrometry.
AB  - The hydrogen-exchange behavior of the low-pH molten globule of human alpha
      lactalbumin, containing all four disulfides, has been examined and compared with
      that of a single disulfide variant, [28-111] alpha-lactalbumin, and of a series
      of proline variants of [28-111] alpha-lactalbumin. The small differences in
      hydrogen-exchange protection exhibited by these partially folded species were
      compared by mixing two or more proteins and monitoring their exchange
      simultaneously using mass spectrometry. The effect of single proline mutations
      within each alpha-domain helix on hydrogen-exchange protection has been
      investigated using six proline variants of [28-111] alpha-lactalbumin, L11P,
      L12P, M30P, I95P, K108P and Q117P. The results show that proline mutations in the
      A, B, C and D alpha-helices lead to a loss of hydrogen-exchange protection for
      residues in the local helix without perturbing hydrogen-exchange protection in
      other regions of the protein. Thus, local unfolding of the A, B, C and D helices
      does not significantly alter the packing and solvent accessibility of other
      regions of the molten globule. By contrast, introduction of a proline residue in
      the C-terminal 3(10) helix produces a larger and more widespread loss of hydrogen
      exchange protection, demonstrating that longer-range perturbations of the molten
      globule have occurred. Thus, residues in this C-terminal region must be involved
      in contacts that are critical for the stabilisation of the compact molten globule
      structure.

PMID- 11518540
TI  - Non-enzymatic glycosylation of a type I collagen matrix: effects on osteoblastic
      development and oxidative stress.
AB  - BACKGROUND: The tissue accumulation of protein-bound advanced glycation
      endproducts (AGE) may be involved in the etiology of diabetic chronic
      complications, including osteopenia. The aim of this study was to investigate the
      effect of an AGE-modified type I collagen substratum on the adhesion, spreading,
      proliferation and differentiation of rat osteosarcoma UMR106 and mouse non
      transformed MC3T3E1 osteoblastic cells. We also studied the role of reactive
      oxygen species (ROS) and nitric oxide synthase (NOS) expression on these AGE
      collagen mediated effects. RESULTS: AGE-collagen decreased the adhesion of UMR106
      cells, but had no effect on the attachment of MC3T3E1 cells. In the UMR106 cell
      line, AGE-collagen also inhibited cellular proliferation, spreading and alkaline
      phosphatase (ALP) activity. In preosteoblastic MC3T3E1 cells (24-hour culture),
      proliferation and spreading were significantly increased by AGE-collagen. After
      one week of culture (differentiated MC3T3E1 osteoblasts) AGE-collagen inhibited
      ALP activity, but had no effect on cell number. In mineralizing MC3T3E1 cells (3
      week culture) AGE-collagen induced a decrease in the number of surviving cells
      and of extracellular nodules of mineralization, without modifying their ALP
      activity. Intracellular ROS production, measured after a 48-hour culture, was
      decreased by AGE-collagen in MC3T3E1 cells, but was increased by AGE-collagen in
      UMR106 cells. After a 24-hour culture, AGE-collagen increased the expression of
      endothelial and inducible NOS, in both osteoblastic cell lines. CONCLUSIONS:
      These results suggest that the accumulation of AGE on bone extracellular matrix
      could regulate the proliferation and differentiation of osteoblastic cells. These
      effects appear to depend on the stage of osteoblastic development, and possibly
      involve the modulation of NOS expression and intracellular ROS pathways.

PMID- 11518541
TI  - Alterations induced by chronic stress in lymphocyte subsets of blood and primary
      and secondary immune organs of mice.
AB  - BACKGROUND: The immune system is particularly sensitive to stress. Although acute
      stress generally has positive effects, chronic stress typically provokes
      immunosuppression. The elucidation of the mechanisms involved in
      immunosuppression are of interest for the design of therapeutic approaches to
      avoid the appearance of stress disorders. This study aimed to investigate chronic
      stress-induced alterations on lymphocyte subset distribution and percentages. The
      experiments were performed with C57BL/6 mice subjected to chronic immobilization
      stress. RESULTS: Stress caused a marked increase in apoptosis inside the thymus,
      and a reduction in the total number of thymocytes. Furthermore, the proportion of
      immature thymocytes declined significantly suggesting that the increased
      apoptosis mainly affected cells of immature phenotype. In blood, the total number
      of lymphocytes diminished but not all lymphocyte populations showed the same
      tendency: while the relative proportion of B cells declined slightly, the
      relative proportion of circulating CD3+ cells, and particularly some T cell
      subsets showing an immature phenotype (CD3+PNA+), increased under stress. The
      spleen and lymph nodes show a marked reduction in cellularity, but the relative
      proportion of T cells increased, while no change or only a slight reduction was
      observed in the relative proportion of B cells. Similarly, the relative
      proportion of T cells increased in bone marrow. CONCLUSIONS: Detailed data on the
      alterations of lymphoid cell subsets occurring under immobilization stress, both
      in the bloodstream and in different lymphoid tissues, are obtained. In general, T
      cells are more affected than B cells and, in particular, a marked increase in the
      percentage of a subset of circulating PNA+CD3+ T cells is observed.

PMID- 11518542
TI  - Risk factors for acquisition of hepatitis C virus infection: a case series and
      potential implications for disease surveillance.
AB  - BACKGROUND: Transmission of hepatitis C virus (HCV) is strongly associated with
      use of contaminated blood products and injection drugs. Other "non-parental"
      modes of transmission including sexual activity have been increasingly
      recognized. We examined risk factors for acquiring HCV in patients who were
      referred to two tertiary care centers and enrolled in an antiviral therapy
      protocol. METHODS: Interviews of 148 patients were conducted apart from their
      physician evaluation using a structured questionnaire covering demographics and
      risk factors for HCV acquisition. RESULTS: Risk factors (blood products,
      injection/intranasal drugs, razor blades/ toothbrushes, body/ear piercing,
      occupational exposure, sexual activity) were identified in 141 (95.3%) of
      participants; 23 (15.5%) had one (most frequently blood or drug exposure), 41
      (27.7%) had two, and 84 (53.4%) had more than two risk factors. No patient
      reported sexual activity as a sole risk factor. Body piercing accounted for a
      high number of exposures in women. Men were more likely to have exposure to
      street drugs but less exposure to blood products than women. Blood product
      exposure was less common in younger than older HCV patients. CONCLUSION: One and
      often multiple risk factors could be identified in nearly all HCV-infected
      patients seen in a referral practice. None named sexual transmission as the sole
      risk factor. The development of a more complete profile of factors contributing
      to transmission of HCV infection may assist in clinical and preventive efforts.
      The recognition of the potential presence of multiple risk factors may have
      important implications in the approach to HCV surveillance, and particularly the
      use of hierarchical algorithms in the study of risk factors.

PMID- 11518543
TI  - Long-term cultivation of colorectal carcinoma cells with anti-cancer drugs
      induces drug resistance and telomere elongation: an in vitro study.
AB  - BACKGROUND: The role of telomerase activation in the expression and/or
      maintenance of drug resistance is not clearly understood. Therefore, we
      investigated the relationships, among the telomerase activity, telomere length
      and the expression of multidrug resistance genes in colorectal cancer cell lines
      cultivated with anti-cancer drugs. METHODS: LoVo and DLD-1 cells were
      continuously grown in the presence of both CDDP and 5-FU for up to 100 days. Cell
      proliferation, telomerase activity, telomere length and the expression of
      multidrug resistance genes were serially monitored as the PDL increased. RESULTS:
      The expression of multidrug resistance genes tended to increase as the PDL
      increased. However, an abnormal aneuploid clone was not detected as far as the
      cells were monitored by a DNA histogram analysis. Tumor cells showing resistance
      to anti-cancer drugs revealed a higher cell proliferation rate. The telomere
      length gradually increased with a progressive PDL. The telomerase activity
      reached a maximum level at 15 PDL in LoVo cells and at 27 PDL in DLD-1 cells. An
      increase in the mRNA expression of the telomerase components, especially in hTERT
      and in hTR, was observed at the same PDLs. CONCLUSIONS: These results suggest
      that a high telomerase activity and an elongation of telomeres both appear to
      help maintain and/or increase drug resistance in colorectal cancer cells. Cancer
      cells with long telomeres and a high proliferative activity may thus be able to
      better survive exposure to anti-cancer drugs. This is presumably due to an
      increased chromosome stability and a strong expression of both mdr-1 and MRP
      genes.

PMID- 11518544
TI  - Organochlorine exposures influence on breast cancer risk and survival according
      to estrogen receptor status: a Danish cohort-nested case-control study.
AB  - BACKGROUND: The relationship between breast cancer and organochlorine exposure is
      controversial and complex. As estrogen receptor positive and negative breast
      cancer may represent different entities of the disease, this study was undertaken
      to evaluate organochlorines influence on breast cancer risk and survival
      according to receptor status. METHODS: The background material stems from the
      Copenhagen City Heart Study (Denmark 1976-78). The breast cancer risk was
      investigated in a cohort nested case-control design including 161 cases and twice
      as many breast cancer free controls. The cases served as a cohort in the survival
      analysis. Serum organochlorine concentrations were determined by
      gaschromotography. RESULTS: The observed increased breast cancer risk associated
      with exposure to dieldrin derived from women who developed an estrogen receptor
      negative (ERN) tumor (Odds ratio [OR] I vs. IV quartile, 7.6, 95% confidence
      interval [95% CI] 1.4-46.1, p-value for linear trend 0.01). Tumors in women with
      the highest dieldrin serum level were larger and more often spread at the time of
      diagnosis than ERP tumors. The risk of dying was for the remaining evaluated
      compounds higher among patients with ERP breast cancer when compared to those
      with ERN. In the highest quartile of polychlorinated biphenyls (SigmaPCB) it was
      more than 2-fold increased (Relative risk [RR] I vs. IV quartile, 2.5, 95% CI 1.1
      5.7), but no dose-response relation was apparent. CONCLUSION: The results do not
      suggest that exposure to potential estrogenic organochlorines leads to
      development of an ERP breast cancer. A possible adverse effect on prognosis of
      hormone-responsive breast cancers needs to be clarified.

PMID- 11518545
TI  - Potential role and chronology of abnormal expression of the Deleted in Colon
      Cancer (DCC) and the p53 proteins in the development of gastric cancer.
AB  - BACKGROUND: Loss of activity of tumor suppressor genes is considered a
      fundamental step in a genetic model of carcinogenesis. Altered expression of the
      p53 and the Deleted in Colon Cancer (DCC) proteins has been described in gastric
      cancer and this event may have a role in the development of the disease.
      According to this hypothesis, we investigated the p53 and the DCC proteins
      expression in different stages of gastric carcinomas. METHODS: An
      immunohistochemical analysis for detection of p53 and DCC proteins expression was
      performed in tumor tissue samples of patients with UICC stage I and II gastric
      cancer. For the purpose of the analysis, the staining results were related to the
      pathologic data and compared between stage categories. RESULTS: Ninety-four cases
      of gastric cancer were analyzed. Disease stage categories were pT1N0 in 23 cases,
      pT2N0 in 20 cases, pT3N0 in 20 cases and pT1-3 with nodal involvement in 31
      cases. Stage pT1-2N0 tumors maintained a positive DCC expression while it was
      abolished in pT3N0 tumors (p <.001). A significant higher proportion of patients
      with N2 nodal involvement showed DCC negative tumors. In muscular-invading tumors
      (pT2-3N0) the majority of cases showed p53 overexpression, whereas a
      significantly higher proportion of cases confined into the mucosa (pT1N0) showed
      p53 negative tumors. Also, a higher frequency of p53 overexpression was detected
      in cases with N1 and N2 metastatic lymph nodal involvement. CONCLUSIONS: Altered
      expression of both DCC and p53 proteins is detectable in gastric carcinomas. It
      seems that loss of wild-type p53 gene function and consequent p53 overexpression
      may be involved in early stages of tumor progression while DCC abnormalities are
      a late event.

PMID- 11518546
TI  - MCMV induces neointima in IFN-gammaR-/- mice: intimal cell apoptosis and
      persistent proliferation of myofibroblasts.
AB  - BACKGROUND: CMV infections have been linked to vasculopathies like
      atherosclerosis and Scleroderma. CMV infects vascular endothelium with
      intermittent shedding of the virus and the development of latency. METHODS: We
      adopted a model of arteritis, developed by Presti et al. (1998), triggered by
      murine cytomegalovirus (MCMV) infection. Our studies focused on neointima
      formation. Groups of mice include: 1) immunocompetent 129S, 2) immunocompetent
      129S receiving whole body irradiation and MCMV, 3) IFN-gammaR-/- receiving MCMV,
      and 4) IFN-gammaR-/- receiving MCMV and whole body irradiation. RESULTS: Mice
      were inoculated with MCMV (5 x 10(4) or 1 x 10(5) PFU's) by i.p. injection;
      hearts and abdominal aortas were collected and histopathology evaluated. Infected
      immunocompetent animals exhibited widespread perivascular inflammation, which
      subsided by 8 weeks. Intimal pathology was not observed in any control group.
      Immunocompetent animals receiving MCMV and irradiation developed mild to moderate
      intimal lesions associated with medial and adventitial inflammation. IFN-gammaR-/
      mice infected for 4 months and receiving whole body irradiation 2 months after
      infection developed pathology characterized by extensive adventitial and medial
      infiltrate and significant neointima, suggesting that infection and
      immunosuppression were co-requisites of neointima formation. Immunohistochemical
      analysis revealed myofibroblasts as a major component of neointima. The disease
      is characterized by up-regulation of growth factors (TGF-beta1, PDGF-A and B).
      Apoptosis was detected in the intimal layer of affected aortas. Active
      proliferation of myofibroblasts and infiltrating cells was also detected.
      CONCLUSION: These results indicate that CMV infections may lead to intimal injury
      that results in the formation of neointima characteristic of autoimmune
      vasculopathies.

PMID- 11518547
TI  - Cultured Kaposi's sarcoma tumor cells exhibit a chemokine receptor repertoire
      that does not allow infection by HIV-1.
AB  - BACKGROUND: HIV-1 is known to play a critical role in the pathogenesis of AIDS
      associated Kaposi's sarcoma (KS). However, it remains controversial whether KS
      cells are target cells for HIV infection. The aim of this study was to
      investigate the expression of chemokine receptors in KS cell cultures and to
      determine whether these cells can be infected by HIV-1. MATERIAL AND METHODS: KS
      derived cells and KS-Y1 cells were investigated using RT-PCR for the expression
      of CD4, CCR3, CCR5, CCR8 and CXCR4 mRNA. HIV infectivity of these cells was
      determined by p24 antigen and HIV-1 RNA production, as well as by HIV-1 DNA
      integration. RESULTS AND DISCUSSION: With the exception of CCR8 which is
      expressed by KS-derived spindle cell cultures but not by KS-Y1 cells,
      unstimulated KS cells express no significant levels of CD4, CCR3, CCR5 or CXCR4
      mRNA. HIV infectivity assays showed that KS cells were unpermissive to HTLVIIIB
      and JRFL strains. Although the expression of CXCR4 mRNA could be upregulated by
      interleukin-1beta, stimulation of KS cells by this cytokine did not allow
      infection by HIV-1. CONCLUSIONS: This shows that KS cells exhibit a chemokine
      receptor repertoire that does not allow infection by HIV-1. Other cell types
      making up KS lesions, such as inflammatory cells, are likely to represent the
      source of HIV-1 products cooperating to promote KS development and progression.

PMID- 11518549
TI  - DC links with global partners.

PMID- 11518550
TI  - Food for thought.

PMID- 11518548
TI  - Systematic reviews of complementary therapies - an annotated bibliography. Part
      2: herbal medicine.
AB  - BACKGROUND: Complementary therapies are widespread but controversial. We aim to
      provide a comprehensive collection and a summary of systematic reviews of
      clinical trials in three major complementary therapies (acupuncture, herbal
      medicine, homeopathy). This article is dealing with herbal medicine. Potentially
      relevant reviews were searched through the register of the Cochrane Complementary
      Medicine Field, the Cochrane Library, Medline, and bibliographies of articles and
      books. To be included articles had to review prospective clinical trials of
      herbal medicines; had to describe review methods explicitly; had to be published;
      and had to focus on treatment effects. Information on conditions, interventions,
      methods, results and conclusions was extracted using a pre-tested form and
      summarized descriptively. RESULTS: From a total of 79 potentially relevant
      reviews pre-selected in the screening process 58 met the inclusion criteria.
      Thirty of the reports reviewed ginkgo (for dementia, intermittent claudication,
      tinnitus, and macular degeneration), hypericum (for depression) or garlic
      preparations (for cardiovascular risk factors and lower limb atherosclerosis).
      The quality of primary studies was criticized in the majority of the reviews.
      Most reviews judged the available evidence as promising but definitive
      conclusions were rarely possible. CONCLUSIONS: Systematic reviews are available
      on a broad range of herbal preparations prescribed for defined conditions. There
      is very little evidence on the effectiveness of herbalism as practised by
      specialist herbalists who combine herbs and use unconventional diagnosis.

PMID- 11518551
TI  - Nutritional guidelines for persons infected with the hepatitis C virus: a review
      of the literature.
AB  - Hepatitis C virus (HCV) is one of the leading causes of chronic liver disease. It
      was first identified in 1989, as being distinct from hepatitis A and hepatitis B.
      The HCV does not attack the immune system, but rather causes an inflammatory
      reaction that is localized within the liver, involving the entire organ. About
      80% of patients with acute hepatitis C will develop chronic HCV, of which about
      20-30% will progress to cirrhosis and its consequences, over 10-20 years. After
      20-40 years, a smaller proportion of patients with chronic disease will develop
      hepatocellular carcinoma. The course and outcome of the disease vary
      considerably. In some individuals, spontaneous remission occurs over a few years;
      in others, the disease is more severe, progressing to cirrhosis and end-stage
      liver disease. Despite biochemical and pathological confirmation of the
      diagnosis, patients are often asymptomatic for many years. Hepatic failure occurs
      late in the disease. Factors suggesting a poor prognosis include high serum
      transaminase levels, active cirrhosis on liver biopsy, and an increased viral
      load (HCV RNA), as well as associated medical conditions such as alcoholic liver
      disease, hepatitis B viral (HBV) infection, or human immunodeficiency virus
      (HIV). Nutrition has been recognized as a prognostic indicator in patients with
      chronic liver failure. However, standardized approaches for the diagnosis and
      classification of malnutrition in this population have not been consistently
      applied before implementing nutrition intervention. Common criteria for the
      assessment of malnutrition, weight and body mass index (BMI) for example, do not
      give accurate data in patients with chronic liver disease, complicated by ascites
      and edema. In addition, the chronic inflammatory reaction of liver failure
      progresses slowly, so that subtle nutritional deficits are not obvious at early
      stages of the disease. A review of the literature has been undertaken to identify
      current nutritional guidelines for patients with hepatitis C as well as chronic
      hepatitis.

PMID- 11518552
TI  - Employee reactions to the introduction of a bulk food distribution system in a
      nursing home.
AB  - Decentralized bulk food distribution was implemented in a nursing home. Employees
      working with elderly residents with dementia were asked their opinion of the
      impact of the new system on residents and workload. A convenience sample of 24
      employees (57% of the staff) completed a 31-item, self-administered Likert-scale
      questionnaire that allowed open-ended comments. Responses were subjected to
      descriptive quantitative analysis, and a qualitative approach was used to explore
      themes that emerged in comments. Qualitative analysis indicated that 52% of
      responses were negative in tone, 30% were positive, and 18% were neutral.
      Initially, three categories of comments emerged, with specific multiple themes
      related to the residents (41%), the employees (37%), or the food-service system
      (22%). Most comments in the employee category were negative, and suggested that
      the decentralized food-service system caused hardship for the staff. This problem
      was resolved by adding one staff-hour at the midday meal. One year later, an
      abbreviated repeat survey of 29 employees revealed adaptation and general
      acceptance of the system. Because a motivated patient care staff is essential to
      the successful feeding of nursing home residents with dementia, employees'
      concerns must be considered when operational changes are planned.

PMID- 11518553
TI  - Simple nutrition screening tools for healthcare facilities: development and
      validity assessment.
AB  - The purpose of nutrition screening is to identify individuals at high nutritional
      risk. Given that dietitians cannot always carry out screening in health-care
      facilities, tools should be simple and based on data obtained from the nursing
      admission questionnaire. This study was conducted to develop timely and valid
      tools for screening protein-energy malnutrition (PEM). A dietetic technician
      administered an initial screening tool to 160 subjects recruited from two
      settings. This tool comprised nine PEM risk factors. The sample included 54
      adults in acute care, 57 elderly adults in acute care, and 49 elderly adults in
      long-term care. Dietitians performed comprehensive nutritional assessments to
      determine the validity of this screening tool. Stepwise regression analysis
      revealed significant risk factors among those included in the initial screening.
      These risk factors were considered during development of the first simple
      screening tool, which encompassed body mass index (BMI) and percentage of weight
      loss, and classified subjects as having low or high PEM risk levels. A second
      tool using BMI and albumin level was tested in cases where an albumin measurement
      was available upon admission. These simple tools had validity indices of 75.9% or
      higher, except in adults in acute care; sensitivity was low in this group. The
      tools proved helpful in establishing dietitians' priorities for involvement and
      in initiating early nutritional care.

PMID- 11518554
TI  - Volunteers: our most valuable resource.

PMID- 11518555
TI  - The institutionalization of children's feeding programs in Atlantic Canada.
AB  - This study traces the evolution of children's feeding programs established in
      Atlantic Canada from a few months to over 15 years ago. Our qualitative analysis
      of nine children's feeding programs in Atlantic Canada revealed that they began
      as an ad hoc, community-based effort to feed hungry children. All subsequently
      experienced stress related to community mobilization. In order to recover from
      this stress, programs "routinized," often with fewer volunteers or by adopting
      measures that ensured efficiency and stability. While one program remained
      routinized, others gradually assumed more features of institutionalization as a
      response to externally or internally imposed crises. They did so by adopting
      professional management strategies and often hiring professional personnel. As
      the institutionalized programs continued, they became driven by the need to feed
      themselves, which was often greater than their mission to feed hungry children.
      The challenge for dietitians assisting children's feeding program operators,
      policy makers, children's advocates, and citizens is to reflect upon which
      organizational models of children's feeding programs should be supported.

PMID- 11518556
TI  - Food habits of Canadians: comparison of intakes in adults and adolescents to
      Canada's food guide to healthy eating.
AB  - Over 25 years have elapsed since national food and nutrient intake data became
      available in Canada. Our goal was to describe present dietary intakes based on
      sociodemographic and 24-hour recall dietary interviews with adults and
      adolescents from households across the country. Within a multistage, stratified
      random sample of 80 enumeration areas, 1,543 randomly selected adults (aged 18
      65) were enrolled in the study; 178 adolescents within the sampled households
      also participated. A comparison of food intake with Canada's Food Guide to
      Healthy Eating indicated that only males aged 13-34 met the minimum recommended
      intake levels for all four food groups. Mean milk products intake was below the
      minimum recommended level for all age groups of females and for men aged 35-65
      years. Adolescent girls had low intakes of meat and alternatives. Daily grain
      product intakes were below five servings for women aged 50-65, as were vegetable
      and fruit intakes for women aged 18-40. Food choices from the "other foods" group
      contributed over 25% of energy and fat intake for all age and gender groups.
      These up-to-date data will be useful to dietitians, nutrition researchers,
      industry, and government in their efforts to promote Canadians' continued
      progress toward meeting food intake recommendations.

PMID- 11518557
TI  - [Maternal anemia in the southeast and northeast regions of New Brunswick and the
      impact on hematological parameters and the growth of the newborn].
AB  - The prevalence of anaemia remains a major nutritional problem in industrialized
      countries. The aim of this study was to compare the prevalence of maternal
      anaemia in southeastern and northeastern areas of New Brunswick and to identify a
      potential interaction between maternal haematologic indices and the growth,
      hemoglobin (Hb) and hematocrit (Ht) of newborns. In this retrospective study, 952
      obstetric and paediatric records, including 654 from the southeastern area
      (Greater Moncton) and the rest from the northeastern area (Acadian Peninsula) of
      New Brunswick, were investigated. The prevalence of maternal anaemia was 21.4% in
      the Greater Moncton area, compared to 11.5% in the Peninsula. The majority of
      anaemic women suffered from a light form of anaemia, mainly in the third
      trimester. Immediately after delivery, 52% of women from Greater Moncton and 40%
      from the Acadian Peninsula had Hb below normal. A positive correlation was
      observed between maternal Hb and newborn Hb and between maternal Ht and newborn
      Hb. Results indicate that maternal anaemia is prevalent in both areas under study
      and confirm the importance of implementing effective prevention measures.

PMID- 11518558
TI  - Development of a validated food frequency questionnaire to determine folate
      intake.
AB  - The aim of this study was to develop and validate a food frequency questionnaire
      (FFQ) to assess the folate intake of women of childbearing age (between 18 and 45
      years). An FFQ containing 140 foods that have the potential to contribute
      significantly to folate intake was developed. The FFQ was pretested by comparing
      it with three-day food records completed by 20 women living in Vancouver, British
      Columbia. The 140-item FFQ overestimated mean daily folate intake (546 +/- 145
      mg/day versus 385 +/- 151 mg/day with three-day food records); the two methods
      were not correlated (r = 0.359, p = 0.143). The FFQ was revised to better
      represent usual folate intake, and the 140 items were reduced to 81. The 81-item
      FFQ was validated with 17 women who completed the FFQ and a seven-day food record
      over four weeks. The mean daily folate intakes were 421 +/- 136 mg/day and 376 +/
      87 mg/day for the FFQ and the food records, respectively; the two methods were
      significantly correlated (r = 0.512, p = 0.036). This study resulted in a
      validated FFQ that can be used as an instrument to determine folate intakes in
      similar populations.

PMID- 11518559
TI  - Food biotechnology: dietitians' resource needs as determined by selected Canadian
      key informants.
AB  - In a 1996 quantitative survey, we assessed selected Canadian dietitians'
      knowledge and attitudes toward biotechnology, particularly genetically altered
      foods. The results showed that, on average, dietitians held unfavourable
      attitudes and were concerned about safety and labelling issues. In the current
      study, qualitative methodology was used to explore dietitians' views on
      controversial issues and to investigate the adequacy of current biotechnology
      resources. Nationwide telephone interviews of 22 key informant dietitians were
      conducted in February and March 1999. Issues covered were food safety and
      quality, labelling, regulations, food production, education, and biotechnology
      resource needs. Findings indicated that dietitians' perspectives on biotechnology
      are diverse nationwide. Views about how biotechnology may affect small producers,
      the local economy, food choices, and food quality varied from very positive to
      very negative. Dietitians indicated a need for more education through discussions
      involving critical analysis and debate by various stakeholders. Respondents
      agreed that the national organization, Dietitians of Canada, has a role to play
      in continuing education. Most participants felt that more concise, balanced, and
      objective resources are needed. Further exploration of dietitians' educational
      needs would help in the development of appropriate educational materials and
      programs for nutrition professionals.

PMID- 11518560
TI  - Fluorescent verapamil analogue for monitoring acidic intracellular organelles in
      multidrug resistant and sensitive cells.
AB  - Resistance to chemotherapeutic agent is a major cause of treatment failure in
      patients with cancer. In many cases, the primaly mechanism leading to a multidrug
      resistant phenotype is the plasma-membrane localized overexpression of drug
      efflux transporters, such as P-glycoprotein. However, acidic intracellular
      organelles seem also to participate in resistance to chemotherapeutic drugs and
      the determination of the pH of these organelles is of importance. In the present
      study we have used a new fluorescent derivative of verapamil, 2-2-diphenyl-5
      [(methylaminomethyl)anthracene] pentanenitrile (EDP 96), and show that it is an
      efficient inhibitor of the P-gp-mediated efflux of anthracycline in K562
      resistant cells. The fluorescence of EDP 96 is environmental and pH sensitive.
      EDP 96 is a weak base (pKa=6.0) and its accumulation into K562 cells is
      accompanied by a significant fluorescence increase due to its entry of the drug
      into acidic regions in the cells. We have used this properties to develop a new
      method to accurately determine the pH of acidic organelle.

PMID- 11518561
TI  - Cytotoxicity, DNA binding and localisation of novel bis-naphthalimidopropyl
      polyamine derivatives.
AB  - Bis-naphthalimidopropyl spermidine (BNIPSpd), spermine (BNIPSpm) and oxa-spermine
      (BNIPOSpm) showed high in vitro cytotoxicity against human breast cancer MCF-7
      cells with IC(50) values of 1.38, 2.91 and 8.45 microM, respectively. These
      compounds were found to effectively displace the intercalating agent ethidium
      bromide bound to the calf thymus DNA using fluorimetric methods (C(50) 0.08-0.12
      microM) and their apparent equilibrium binding constants (K(app)) were calculated
      to be in the range of 10.5-18 x 10(7) M(-1). Furthermore, strong stabilisation of
      calf thymus DNA duplex in the presence of bis-naphthalimidopropyl polyamine
      derivatives (BNIPSpd, BNIPSpm and BNIPOSpm) was observed by UV spectrophotometric
      analysis (T(m)=93.3-97 degrees C compared with 75 degrees C for calf thymus DNA
      without drug). Because of their inherent fluorescence, these compounds were
      localised preferentially inside the nucleus as evidenced by their direct
      observation under the fluorescence microscope. The results obtained suggest that
      the cytotoxic activity of the bis-naphthalimidopropyl polyamines may be in part,
      caused by their effects on DNA.

PMID- 11518562
TI  - Structure-activity relationships in the deacetylation of O-glucosides of N
      hydroxy-N-arylacylamides by mammalian liver microsomes.
AB  - Structure-activity relationships in the deacylation of O-glucosides of N-hydroxy
      N-aryl-acylamides were investigated to provide insights into the metabolic
      activation of carcinogenic/mutagenic O-glycosides of N-hydroxy-N-arylacylamides.
      In the subcellular fractions obtained from porcine liver, the deacetylation
      activity toward O-glucoside of N-hydroxyacetanilide (GAc) was mainly localized in
      the microsomes. Both the 2-chloro (2ClGAc) and 2-methyl (2MeGAc) derivatives of
      GAc were not deacetylated by the microsomes. Other compounds having either 3- or
      4-substituent (chloro or methyl), however, were deacetylated and showed higher
      V(max)/K(m) values than that of GAc. 4-Methyl derivative (4MeGAc) was shown to
      competitively inhibit the deacetylation activity toward GAc, and the K(i) value
      of 4MeGAc was comparable with its K(m) value obtained in the microsome-catalyzed
      deacetylation. These apparent K(m) values were shown to correspond to their
      lipophilicities estimated from retention times on high-performance liquid
      chromatography (HPLC). As for the effect of acyl groups, the order of V(max)/K(m)
      values was N-propionyl derivative (GPr)>GAc>N-butyryl derivative (GBu). From the
      optimized structures and energy levels of the frontier orbitals of these
      compounds, calculated by the semi-empirical AM1 method, the effects of 2
      substituents and acyl groups on the deacetylation activity is thought to be due
      to a steric factor. From the energy levels of the frontier orbitals of GAc and
      its 3- or 4-substituted derivatives, the compound having a lower level of LUMO
      was shown to be deacetylated effectively. There were marked species differences
      in the microsomal deacetylation activity toward GAc, and the highest activity was
      found in the rabbit, followed by the porcine, hamster, rat and then bovine liver
      microsomes.

PMID- 11518563
TI  - Effects of Ginkgo biloba extract (EGb 761) and quercetin on lipopolysaccharide
      induced release of nitric oxide.
AB  - Administration of bacterial lipopolysaccharide (LPS) to laboratory animals and
      cultured macrophages is known to induce the production of nitric oxide (NO) from
      inducible nitric oxide synthase (iNOS). Here we show that pre-treatment with
      Ginkgo biloba extract (EGb 761) suppresses the in vivo production of NO (measured
      by the Griess reaction) after challenge with LPS. In order to begin to understand
      the mechanism of this inhibition, we evaluated in vitro effects of EGb 761 and
      its flavonoid component, quercetin, on LPS-treated RAW 264.7 macrophages. Pre
      treatment with EGb 761 or quercetin dose-dependently inhibited NO release. Both
      substances scavenged NO generated from the decomposition of sodium nitroprusside.
      Western analysis showed that EGb 761 and quercetin inhibited LPS-induced levels
      of iNOS protein. Northern blotting demonstrated that EGb 761 and quercetin
      decreased LPS-induced iNOS mRNA levels without altering the half-life. Activation
      of mitogen activated protein kinases (MAPKs) and the redox-sensitive
      transcription factors, nuclear factor-kappaB (NF-kappaB) and activator protein 1
      (AP-1) are key events in the signal transduction pathways mediating iNOS
      induction. In our studies, both EGb 761 and quercetin inhibited p38 MAPK
      activity, which is necessary for iNOS expression in LPS-stimulated RAW 264.7
      macrophages. However, differences in the response of NF-kappaB, AP-1, and Jun N
      terminal kinase/stress activated protein kinase (JNK/SAPK) and its downstream
      substrates to EGb 761 and quercetin suggest that quercetin is not the sole
      component responsible for the in vivo inhibition of LPS-induced iNOS activation
      by EGb 761.

PMID- 11518564
TI  - Prooxidant and antioxidant activities of bilirubin and its metabolic precursor
      biliverdin: a structure-activity study.
AB  - Bilirubin, which is derived from its metabolic precursor biliverdin, is the end
      product of heme catabolism. It has been proposed as a physiological antioxidant
      present in human extracellular fluids. We have earlier shown that bilirubin in
      the presence of the transition metal ion Cu(II) causes strand cleavage in DNA
      through generation of reactive oxygen species, particularly the hydroxyl radical.
      Thus bilirubin possesses both antioxidant and prooxidant properties. In order to
      understand the chemical basis of various biological properties of bilirubin, we
      have studied the structure-activity relationship between bilirubin and its
      precursor biliverdin. The latter has also been reported to possess both
      antioxidant and toxic properties. In the present studies bilirubin was found to
      be more effective in the DNA cleavage reaction and a more efficient reducer of
      Cu(II). The rate of formation of hydrogen peroxide and hydroxyl radicals by the
      compounds also showed a similar pattern. The relative antioxidant activity was
      also examined by studying the effect of these compounds on DNA cleavage by a
      hydroxyl radical generating system and their quenching effect on hydroxyl
      radicals. The results indicate that bilirubin is more active both as an
      antioxidant as well as an oxidative DNA cleaving agent. A model for binding of
      copper to bilirubin has been proposed where two copper ions are bound to two
      molecules of bilirubin through their terminal pyrrole nitrogens. In order to
      account for the enhanced copper reducing capacity of bilirubin we have further
      proposed that an additional copper binding site is provided for in the case of
      bilirubin due to the absence of a double bond between pyrrole rings II and III.
      Further it would appear that the structural features of the bilirubin molecule
      which are important for its prooxidant action are also the ones that render it a
      more effective antioxidant.

PMID- 11518565
TI  - Roles of vitamin C in radiation-induced DNA damage in presence and absence of
      copper.
AB  - Exposure to either ionizing radiation or certain transition metals results in
      generation of reactive oxygen species that induce DNA damage, mutation, and
      cancer. Vitamin C (a reactive oxygen scavenger) is considered to be a dietary
      radioprotective agent. However, it has been reported to be genotoxic in the
      presence of certain transition metals, including copper. In order to explore the
      capacity of vitamin C to protect DNA from radiation-induced damage, and the
      influence of the presence of copper on this protection, we investigated vitamin C
      mediated protection against radiation-induced damage to calf thymus DNA in vitro
      in the presence or absence of copper(II). Vitamin C (0.08-8.00 mM, pH 7.0)
      significantly reduced DNA damage induced by gamma-irradiation (30-150 Gy) by 30
      50%, similar to the protective effect of glutathione. However, vitamin C plus
      copper (50 microM) significantly enhanced gamma-radiation-induced DNA damage. Low
      levels of added copper (5 microM), or chelation of copper with 1-N
      benzyltriethylenetetraine tetrahydrochloride (BzTrien) and bathocuprinedisulfonic
      acid (BCSA), abolished the enhanced damage without diminishing the protective
      effect of vitamin C. These results indicate that vitamin C can act as: (1) an
      antioxidant to protect DNA damage from ionizing radiation; and (2) a reducing
      agent in the presence of copper to induce DNA damage. These effects are important
      in assessing the role of vitamin C, in the presence of mineral supplements or
      radioprotective therapeutic agents, particularly in patients with abnormally high
      tissue copper levels.

PMID- 11518566
TI  - On the role of alkylating mechanisms, O-alkylation and DNA-repair in genotoxicity
      and mutagenicity of alkylating methanesulfonates of widely varying structures in
      bacterial systems.
AB  - The Ames test and the SOS-chromotest are widely used bacterial
      mutagenicity/genotoxicity assays to test potential carcinogens. Though the
      molecular mechanisms leading to backmutations and to the induction of SOS-repair
      are in principle known the role of alkylation mechanisms, of different DNA
      lesions and of DNA-repair is in parts still unknown. In this study we
      investigated 14 monofunctional methanesulfonates of widely varying structures for
      mutagenicity in Salmonella typhimurium strain TA 1535 sensitive for O(6)-guanine
      alkylation for comparison with strain TA 100 in order to obtain additional
      information on the role of alkylation mechanisms, formation of the
      procarcinogenic DNA-lesion O(6)-alkylguanine and the role of DNA-repair in
      induction of backmutation. The substances were also tested in the SOS-chromotest
      with Escherichia coli strain PQ 37 and strain PQ 243 lacking alkyl base
      glycosylases important for base excision repair in order to examine the role of
      alkylation mechanisms, of base excision repair and the role of O-alkyl and N
      alkyl DNA-lesions on the induction of SOS-repair. The secondary methanesulfonates
      with very high S(N)1-reactivity isopropyl methanesulfonate and 2-butyl
      methanesulfonate showed highest mutagenicities in both strains. The higher
      substituted methanesulfonates with very high S(N)1-reactivity had lower mutagenic
      activities because of reduced half lives due to their high hydrolysis rates. A
      clear increase in mutagenicities in strain TA 100 was observed for the primary
      compounds methyl methanesulfonate and allyl methanesulfonate with very high S(N)2
      reactivity. The primary compound phenylethyl methanesulfonate has a relatively
      high mutagenicity in both Salmonella strains which can be explained by an
      increased S(N)1-reactivity and by low repair of the O(6)-phenylethylguanine.
      Highest SOSIPs (SOS inducing potency) in strains PQ 37 and PQ 243 were found for
      methyl methanesulfonate and for the secondary compounds with high S(N)1
      reactivity. The ratios in the SOSIPs between strain PQ 243 and PQ 37, indirectly
      indicative for the role of O- and N-alkylation in the induction of SOS-repair,
      was high for the primary methanesulfonates and lower for the secondary,
      indicating that the SOS-repair is, to a certain extent, also induced by other
      lesions than O(6)-alkylation. The results indicate that O(6)-alkylation is also a
      predominant lesion for backmutation in strain TA 100 and that in the case of
      monofunctional alkylating agents high S(N)2-reactivities are required to induce
      error prone repair mediated backmutations. The O(6)-alkylguanine lesion is also
      important for induction of SOS-repair in the SOS-chromotest, however, other sites
      of alkylation which are repaired by the base pair excision repair system can also
      efficiently contribute to the induction of SOS-repair.

PMID- 11518567
TI  - Carotenoid incorporation into natural membranes from artificial carriers:
      liposomes and beta-cyclodextrins.
AB  - Liposomes and beta-cyclodextrin (beta-CD) have been used as carriers for the
      incorporation of three dietary carotenoids (beta-carotene (BC), lutein (LUT) and
      canthaxanthin (CTX)) into plasma, mitochondrial, microsomal and nuclear membrane
      fractions from pig liver cells or the retinal epithelial cell line D407. The
      uptake dynamics of the carotenoids from the carriers to the organelle membranes
      and their incorporation yield (IY) was followed by incubations at pH 7.4 for up
      to 3 h. The mean IYs saturated between 0.1 and 0.9 after 10-30 min of incubation,
      depending on membrane characteristics (cholesterol to phospholipid ratio) and
      carotenoid specificity. Mitochondrial membranes (more fluid) favour the
      incorporation of BC (non-polar), while plasma membranes (more rigid) facilitate
      the incorporation of lutein, the most polar carotenoid. A high susceptibility of
      BC to degradation in the microsomal suspension was observed by parallel
      incubations with/without 2,6-di-t-buthyl-p-cresol (BHT) as antioxidant additive.
      The beta-CD carrier showed to be more effective for the incorporation of lutein
      while BC was incorporated equally into natural membranes either from liposomes or
      from cyclodextrins. The presence of cytosol in the incubation mixture had no
      significant effects on the carotenoid incorporations.

PMID- 11518568
TI  - Concentration-dependent, temperature-dependent non-Newtonian viscosity of lung
      surfactant dispersions.
AB  - The bulk shear viscosities of aqueous dispersions of lavaged calf lung surfactant
      (LS) and its chloroform:methanol extract (CLSE) were measured as a function of
      concentration, shear rate and temperature. At 10-mg phospholipid per milliliter,
      dispersions of LS and vortexed CLSE in 0.15 M NaCl (saline) had low viscosities
      near 1 cp over a range of shear rates from 225 to 1125 s(-1). Lung surfactant
      viscosity increased with phospholipid concentration and became strongly non
      Newtonian with higher values at low shear rates. At 37 degrees C and 40 mg/ml, LS
      and vortexed CLSE in saline had viscosities of 38 and 34 cp (77 s(-1)) and 12 and
      7 cp (770 s(-1)), respectively. Viscosity values for LS and CLSE were dependent
      on temperature and, at fixed shear, were lower at 23 degrees C than at 37 or 10
      degrees C. Hysteresis was also present in viscosity measurements depending on
      whether shear rate was successively increased or decreased during study. Addition
      of 5 mM Ca(2+) at 37 degrees C markedly reduced CLSE viscosity at all shear rates
      and decreased LS viscosity at low shear rates. Dispersion by sonication rather
      than vortexing increased the viscosity of CLSE at fixed shear, while synthetic
      phospholipids dispersed by either method had low, relatively Newtonian
      viscosities. The complex viscous behavior of dispersions of LS and CLSE in saline
      results from their heterogeneous aggregated microstructure of phospholipids and
      apoproteins. Viscosity is influenced not only by the aggregate surface area under
      shear, but also by phospholipid-apoprotein interactions and aggregate
      structure/deformability. Similar complexities likely affect the viscosities of
      biologically-derived exogenous surfactant preparations administered to patients
      in clinical surfactant therapy.

PMID- 11518569
TI  - Capability of arsonolipids to transport divalent cations: a Pressman cell study.
AB  - The ability of the newly synthesized arsonolipids (2,3-diacyloxyprophlarsonic
      acids) to transport cations was studied using the Pressman cell. Experimental
      results demonstrate that arsonolipids are much more efficient carriers of Ca(2+)
      and Mg(2+) than natural phosphatidic acid in the Pressman cell experiments. The
      ability of arsonolipids to transfer Ca(2+) is affected by the lipid side chain
      length in the order: C(12)>>C(14) approximately C(16). Ca(2+) is transferred
      faster than Mg(2+), suggesting that the latter is more tightly bound to the
      arsonolipids. The transfer kinetic curves are parabolic for C(12), while
      initially linear with a tendency to reach a steady state for C(14) and C(16),
      when the pH in the donor compartment was 8.3. The transport kinetics for both
      ions studied were best fitted by an equation derived from saturation kinetics
      that apply in reversible chemical reactions. The ion transfer rates increased as
      the pH in the donor compartment decreased.

PMID- 11518570
TI  - Effects of oxygenated sterol on phospholipid bilayer properties: a molecular
      dynamics simulation.
AB  - The properties of dipalmitoylphosphatidylcholine (DPPC):6-ketocholestanol bilayer
      at 50 mol% sterol were studied using the molecular dynamics simulation technique.
      Our simulations were performed at constant pressure and temperature on a
      nanosecond time scale. Data from this simulation were compared to the results of
      our previous simulations on DPPC and DPPC-cholesterol bilayers. We conclude that
      the differences in the properties of membranes with cholesterol and
      ketocholestanol are due to the difference in 6-ketocholestanol and cholesterol
      location in the bilayer. The presence of the keto group in ketocholestanol moves
      the sterol towards the polar region closer to interface with water. We predict
      that similar mechanisms would govern the properties of membranes with other
      oxygenated sterols, such as for example 7-ketocholesterol. Results of our
      simulations are in a good agreement with the data available from the experiment.

PMID- 11518571
TI  - Kinetics of peroxidation of linoleic acid incorporated into DPPC vesicles
      initiated by the thermal decomposition of 2,2'-azobis(2-amidinopropane)
      dihydrochloride.
AB  - In a previous work [Chem. Phys. Lipids 2000 104, 49], we have derived the
      following rate law for the oxidation of lipids in compartmentalized systems:
      R(T)=(k(1)/k(t))(0.5) k(p) [In](0.5) c(0.5) [LH], where, R(T) is the total rate
      of oxidation, k(1) is the rate constant for the production of free radicals, k(t)
      and k(p) are the intra-particle rate constants for the termination and
      propagation sets, respectively, [In] is the concentration of a water-soluble
      initiator, c is the concentration of particles, and [LH] is the intra-particle
      concentration of oxidable lipid. In the present work, we have investigated on the
      applicability of the proposed kinetic rate law for a system where it takes place
      the oxidation of a reactive lipid incorporated into an inert matrix. With this
      purpose, we have measured the rate of oxidation of linoleic acid incorporated
      into dipalmitoylphosphatidylcholine vesicles initiated by the thermal
      decomposition of 2,2'-azobis(2-amidinopropane) dihydrochloride as a function of
      the initiator, particles, and intra-particle LH concentrations. The
      experimentally determined kinetic orders obtained were 0.54+/-0.02, 0.48+/-0.05
      and 0.83+/-0.04 for the dependence of the oxidation rate with initiator,
      particles, and LH intra-particle concentrations, respectively, in agreement with
      those theoretically predicted. The lower value obtained for the kinetic order in
      LH is attributed to a change in k(t) with the increase in oxidable lipid intra
      particle concentration. The main point to be emphazised from the results here
      obtained is that the kinetic rate law for the oxidation of lipids in
      compartmentalized systems can be significantly different than that observed when
      to the oxidation takes place in homogeneous solution.

PMID- 11518572
TI  - Extraction of lipid membrane incorporated vitamin E by sucrose polyesters.
AB  - 2H and 31P solid state NMR have been used to probe, at the molecular level, the
      interaction between structurally different sucrose polyesters and a phospholipid
      membrane into which alpha-tocopherol and specifically deuterated alpha-[5,7
      (2)H(6)] tocopherol has been incorporated. Our results show that at high
      concentration (>or=10 mol%) sucrose octapalmitate (SOP) and sucrose hexapalmitate
      (SHxP) deplete bilayer-associated alpha-tocopherol in dipalmitoyl
      phosphatidalcholine (DPPC) multilamellar dispersions and preferentially sequester
      the alpha-tocopherol into a fluid sucrose polyesters (SPE) phase located proximal
      to the membrane surface. It is demonstrated that the ability of SPEs to function
      as a 'lipophilic sink' depends strongly on sucrose polyester concentration and
      degree of esterification.

PMID- 11518573
TI  - Synthesis of a triantioxidant compound: combination of beta-apo-8'-carotenoic
      acid, selenacapryloic acid and trolox in a triglyceride.
AB  - Carotenoids, vitamin-E and selenium show similar or complementary physiological
      properties and protect against a variety of pathological processes. Mixtures of
      these antioxidants are found in nutritional supplements and are used to prevent
      several diseases. The synthetic connection of carotenoids, vitamin-E and selenium
      may increase the chemopreventive activity of the individual compounds. A
      carotenoic acid, a selena fatty acid and the vitamin-E derivative trolox were
      successively esterified with glycerol to 1-(beta-apo-8'carotenoyl)-2-(7
      selenaoctanoyl)-3-(6-hydroxy-2,5,7,8-tetramethylchroman-2-acyl)-glycerol. This
      triantioxidant compound revealed, in the DPPH (1,1-diphenyl-2-picrylhydrazyl)
      test, an additive affect, consisting of the radical quenching activity of the
      carotenoid and trolox. The DPPH test was not sensitive for the Se moiety in the
      triantioxidant compound.

PMID- 11518574
TI  - Lipid analysis of bronchoalveolar lavage fluid (BAL) by MALDI-TOF mass
      spectrometry and 31P NMR spectroscopy.
AB  - Despite the high clinical relevance, only the cellular moiety of bronchoalveolar
      lavage (BAL) has been intensively investigated and is used for diagnosis
      purposes. On the other hand, the cell-free fluid is, by far, less characterized.
      Although this fluid represents a relatively simple mixture of only a few
      different phospholipids (mainly phosphatidylcholine, phosphatidylglycerol and
      cholesterol), methods for the routine analysis of these fluids are still lacking.
      In the present investigation we have applied, for the first time, MALDI-TOF mass
      spectrometry, as well as 31P NMR spectroscopy to the analysis of organic extracts
      of bronchoalveolar lavage fluids. BAL from different mammals (rat, minipig,
      rabbit and man) were investigated and, for means of comparison, organic extracts
      of lung tissue were also examined. Both applied methods provide fast and reliable
      information on the lipid composition of the bronchoalveolar lavage. However,
      despite of its comparably low sensitivity, 31P NMR spectroscopy detects all
      phospholipid species in a single experiment and with the same sensitivity,
      whereas MALDI-TOF fails in the detection of phosphatidylethanolamine in the
      presence of higher quantities of phosphatidylcholine. In contrast, MALDI-TOF mass
      spectrometry is more suitable for the detection of cholesterol and the
      determination of the fatty acid composition of the individual phospholipids,
      especially lysolipids. It will be shown that all BALs exhibit significant,
      species-dependent differences that mainly concern the content of
      phosphatidylglycerol and lyso-phosphatidylcholine. It is concluded that both
      methods are suitable tools in lipid research due to the (in comparison to
      alternative methods) simplicity of performance.

PMID- 11518575
TI  - Analysis of the diffusion of bile salt/phospholipid micelles in rat intestinal
      mucin.
AB  - The interaction of sodium taurocholate/egg phosphatidylcholine (TC/PC) micelles
      with mucin was determined to investigate the exclusion of lipids by mucus in the
      absorption process. The distribution of TC/PC was assessed at two intermicellar
      and three phospholipid concentrations with isolated, rat intestinal mucin (RIM)
      by dialysis. The diffusion coefficients were measured by NMR spectroscopy. At
      high [PC], RIM had lower [PC] relative to the control, while the concentration of
      TC was largely independent of mucin concentration. The PC diffusion coefficients
      were reduced in the presence of RIM. The magnetization decay of TC was compared
      with simulations to provide estimates of the monomeric diffusivity and exchange
      rate constant. The rate constants increased with increasing micelle
      concentration, and the free TC diffusion coefficient was reduced in the presence
      of mucin. Mucin has an exclusive effect on TC/PC mixed micelles that has been
      quantitatively determined through the use of diffusion measurements of dialyzed
      samples.

PMID- 11518576
TI  - X-ray diffraction study on interdigitated structure of phosphatidylcholines in
      glycerol.
AB  - X-ray diffraction was used to study the interdigitated structure of
      phosphatidylcholines (PCs) in glycerol. In this study, we investigated five
      different saturated diacyl PCs with carbon number from 14 to 18 in their acyl
      chains. It was found that lamellar spacings increase linearly as increasing the
      carbon number in the chains and that the increment is 0.10+/-0.01 nm per one
      carbon atom. The lamellar diffraction intensity data were analyzed, by applying a
      method proposed by Adachi [Chem. Phys. Lipids 107 (2000) 93]. The results
      indicate that the moiety around polar headgroup regions is almost unchanged,
      being independent of the carbon number.

PMID- 11518577
TI  - Phase state of aqueous gelatin-polysaccharide (1)-polysaccharide (2) systems.
AB  - Optical microscopy, ultracentrifugation, phase analysis and turbidimetric
      titration methods were used to study phase state and phase equilibria of
      quaternary water-gelatin-pectin-dextran system in the absence of salts and at pH
      higher than the isoionic point. It was found that these systems are two-phase
      ones, contrary to the single-phase behaviour of the ternary water-gelatin-pectin
      and water-gelatin-dextran systems under the same conditions. The observed phase
      separation is the result of incompatibility of gelatin with pectin, dextran
      molecules being distributed practically uniformly between coexisting phases. This
      phenomenon is rather typical for many water-gelatin-polysaccharide-1
      polysaccharide-2 systems under the conditions when all the pairs of biopolymers
      are compatible. The high compatibility of gelatin with pectin or dextran in the
      ternary systems under given conditions is due to the formation of weakly bonded
      interpolymer complexes. The incompatibility of gelatin with pectin in the
      presence of dextran can be explained by the blockage of the reactive gelatin
      groups due to their competitive interactions with dextran.

PMID- 11518578
TI  - Gamma-ray crosslinking of poly(3-hydroxyoctanoate-co-undecenoate).
AB  - The gamma-ray crosslinking of films made of poly(3-hydroxyoctanoate) containing
      undecenoate moieties (up to 33 mole%) were studied. X-ray diffraction, thermal
      analysis, dynamic mechanical analysis (DMA), solid state nuclear magnetic
      resonance (NMR) spectroscopy and degree of crosslinking (swelling analysis) as a
      function of irradiation dose were evaluated for treatments in air or in N(2)
      atmosphere. After uncrosslinked material was isolated by CHCl(3) extraction,
      solid state NMR data suggested that only a small percentage of the double bonds
      took part in the formation of irradiation crosslinks. Crosslinking in N(2) was
      more efficient than in air and a 20 kGy dose was sufficient for optimal
      crosslinking. The X-ray diffraction patterns of the polymer films were unaffected
      by moderate irradiation. The use of sodium hypochlorite to isolate poly(3
      hydroxyoctanoate-co-undecenoate) samples resulted in partial chlorination of the
      double bonds and considerable depolymerization.

PMID- 11518579
TI  - Blends of aliphatic polyesters. VI. Lipase-catalyzed hydrolysis and visualized
      phase structure of biodegradable blends from poly(epsilon-caprolactone) and
      poly(L-lactide).
AB  - Phase-separated biodegradable polymer blends were prepared from poly(epsilon
      caprolactone) (PCL) and poly(L-lactide) (PLLA), and Rhizopus arrhizus lipase
      catalyzed hydrolysis and phase structure of the blend films were investigated.
      Gravimetry revealed that the lipase-catalyzed hydrolysis of PCL in PCL- and PLLA
      rich phases is disturbed by the presence of PLLA. Polarimetry confirmed the
      occurrence of a predominant hydrolysis of PCL and subsequent removal of the
      hydrolyzed water-soluble PCL oligomers in the blend films. Gravimetry and gel
      permeation chromatography of the non-blended PLLA film indicated that R. arrhizus
      lipase has no catalytic effect on the hydrolysis of PLLA. The phase structure of
      the blend films could be visualized by selective enzymatic removal of one
      component and subsequent scanning electron microscopic observation.

PMID- 11518580
TI  - Structural characteristics and properties of the regenerated silk fibroin
      prepared from formic acid.
AB  - Structural characteristics and thermal and solution properties of the regenerated
      silk fibroin (SF) prepared from formic acid (FU) were compared with those of SF
      from water (AU). According to the turbidity and shear viscosity measurement, SF
      formic acid solution was stable and transparent, no molecular aggregations
      occurred. The sample FU exhibited the beta-sheet structure, while AU random coil
      conformation using Fourier transform infrared (FTIR), X-ray diffraction (XRD),
      and differential scanning calorimetry. The effects of methanol treatment on
      samples were also examined. According to the measurement of crystallinity (XRD)
      and crystallinity index (FTIR), the concept of long/short-range ordered structure
      formation was proposed. Long-range ordered crystallites are predominantly formed
      for methanol treated SF film while SF film cast from formic acid favors the
      formation of short-range ordered structure. The relaxation temperatures of SF
      films measured by dynamic thermomechanical analysis supported the above mechanism
      due to the sensitivity of relaxation temperature on the short-range order.

PMID- 11518581
TI  - Unfolding and inactivation of monomeric superoxide dismutase from E. coli by SDS.
AB  - The inactivation and the unfolding of the naturally monomeric Cu, Zn, superoxide
      dismutase from E. coli upon addition of sodium dodecylsulphate have been studied.
      In contrast to the bovine enzyme, CD, EPR, NMR spectroscopy and pulsed low
      resolution NMR measurements found an unfolding transition followed by
      inactivation of the enzyme. During this transition the active site becomes
      accessible to the bulk water. The unfolding is reversible and both, the
      tridimensional structure of the protein and the active site, can be restored upon
      dialysis. In addition, unfolding occurs without loss of metals in the solution.

PMID- 11518582
TI  - Biosynthesis and structural characterization of medium-chain-length poly(3
      hydroxyalkanoates) produced by Pseudomonas aeruginosa from fatty acids.
AB  - In this study, we investigated the ability of Pseudomonas aeruginosa ATCC 27853
      to grow and synthesize poly(3-hydroxyalkanoates) (PHAs) from saturated fatty
      acids with an even number of carbon atoms, from eight to 22, and from oleic acid.
      In a non-limiting medium, all carbon sources but docosanoic acid supported cell
      growth and PHA production, with eicosanoic acid giving the highest yield. In
      magnesium-limiting conditions, higher yields were obtained from sources with up
      to 16 carbon atoms. Composition was estimated by gas chromatography of
      methanolyzed samples and (13)C nuclear magnetic resonance. The 3-hydroxyalkanoate
      units extended from hexanoate to tetradecanoate or tetradecenoate, with octanoate
      and decanoate as the predominant components. Weight average molecular weights
      ranged from 78,000 to 316,000. Fast atom bombardment mass spectrometry of
      partially pyrolyzed samples, coupled to statistical analysis, showed that these
      PHAs are random copolymers.

PMID- 11518583
TI  - Interactions between apple cell walls and native apple polyphenols:
      quantification and some consequences.
AB  - Cell walls were prepared from apple parenchyma by a phenol:buffer procedure.
      Polyphenols were extracted from freeze-dried apple parenchyma by methanol and
      water:acetone, and purified by preparative HPLC. Interactions were quantified by
      bringing into contact suspended cell walls and polyphenol solutions.
      Hydroxycinnamic acids and (-)-epicatechin did not bind to cell walls. Binding of
      procyanidins was fast and reached up to 0.6 g per g cell walls. The amounts of
      procyanidins bound increased with the initial concentration and with DPn.
      Procyanidins could be partially desorbed by buffer, more being desorbed in the
      presence of dissolved cell wall polysaccharides. They were totally desorbed using
      8 M urea or acetone:water. Higher polymers were bound selectively from
      procyanidin mixtures, and very high average DPn were obtained in extensively
      washed complexes. Binding of procyanidins inhibited enzymic degradation of the
      cell walls.

PMID- 11518584
TI  - NMR local range investigations in amorphous starchy substrates I. Structural
      heterogeneity probed by (13)C CP-MAS NMR.
AB  - The (13)C CP-MAS (Cross Polarization and Magic Angle Spinning) NMR signatures of
      a series of amorphous and semi-crystalline samples prepared from various starchy
      substrates (native potato starch, amylopectin, amylose) following different
      techniques of preparation (casting, freeze drying, solvent exchange) are
      compared. Decompositions of the C1 resonance spectra reveal the existence of four
      or five main types of alpha(1-4) linkages, which can be quantified. The influence
      of the intrinsic primary structure (linear or branched) and of the preparation
      procedure on conformational changes and resulting crystallinity are interpreted
      in terms of distributions of average glycosidic linkages dihedral angles (Phi,
      Psi). The role of hydration is also considered. An improved understanding at
      different structural levels is obtained in relation to local and intermediate
      range orders. Such information may be useful for the understanding of the
      structural evolution of a large variety of starchy substrates before or after
      treatments widely used in industrial processes.

PMID- 11518585
TI  - NMR local range investigations in amorphous starchy substrates: II-Dynamical
      heterogeneity probed by (1)H/(13)C magnetization transfer and 2D WISE solid state
      NMR.
AB  - In the preceding paper, we have investigated the structural heterogeneous
      character of a series of amorphous samples prepared from various starchy
      substrates (native potato starch, amylopectin and amylose) following different
      techniques of preparation (casting, freeze drying and solvent exchange). Spectral
      decompositions of the C1 resonances of the (13)C CP-MAS (Cross Polarization and
      Magic Angle Spinning) spectra under (1)H decoupling have shown the existence of
      five main types of alpha(1-4) linkages. In this part, 2D solid state NMR WISE
      experiments and the (13)C/(1)H magnetization transfer in CP as a local probe for
      both structures and dynamics were used. The (13)C CP magnetization curves versus
      contact time of each C1 component in each recorded spectrum were fitted with an
      analytic function taking into account two (1)H reservoirs. Interpretation of the
      characteristic times derived from fitting yields some improvements on the
      knowledge of the heterogeneity of the samples and on the water molecules
      distribution.

PMID- 11518586
TI  - Hearing habilitation with auditory brainstem implantation in two children with
      cochlear nerve aplasia.
AB  - Patients with aplasia and hypoplasia of the cochlear nerve have no chance of
      having their hearing restored by stimulating the periphery of the auditory system
      using the traditional cochlear implant. A possible approach to auditory
      rehabilitation may be direct electrical stimulation of the cochlear nuclei with
      an auditory brainstem implant (ABI). Recently, two children, aged 4 and 3 years,
      respectively, with bilateral severe cochlear malformations and cochlear nerve
      aplasia received an ABI. The present paper reports the technique and the
      preliminary results of this experience. The classic retrosigmoid approach was
      used. The correct position of the electrodes was estimated with the aid of EABRs
      and neural response telemetry (NRT). No postoperative complications were
      observed. High-resolution CT scans with a bone algorithm reconstruction technique
      were taken postoperatively to evaluate electrode placement before discharge. The
      ABI was activated 30 days after implantation in both patients. To date 16 and 13
      electrodes, respectively, have been activated in the two children. Three months
      after activation the first patient had achieved good environmental sound
      awareness, good speech detection and some speech discrimination. The second
      child, 1 month after activation, had achieved good environmental sound awareness
      and moderate speech detection. To the best of our knowledge this is the first
      report of patients with hypoplasia of the cochlea and aplasia of the cochlear
      nerve, aged below 5 years and treated with an ABI.

PMID- 11518587
TI  - Auditory abnormalities associated with unilateral renal agenesis.
AB  - OBJECTIVE: To evaluate the relationship between unilateral renal agenesis and
      auditory abnormality, and to determine the clinical spectrum of hearing
      impairment in such patients. METHODS: Seventy-five children with unilateral renal
      agenesis underwent auditory examinations. The subjects comprised 35 males and 40
      females. Fourteen females had mullerian abnormalities. Another 75 schoolchildren
      with the same gender profile were selected for audiometric testing as a control
      group. Children with sonographically evident urogenital system abnormalities were
      excluded from the control group. RESULTS: The prevalence of auditory
      abnormalities in children with unilateral renal agenesis (4/75) (5.3%) was higher
      than in the control group (0%). The prevalence in children with urogenital
      anomalies was significantly higher in patients with renal agenesis than in the
      normal population (28.5%). Audiometric results showed that four of the 75
      children manifested ipsilateral sensorineural hearing impairment, particularly in
      the high-frequency range. All were females with coexisting genital abnormalities.
      Two were diagnosed with mild sensorineural hearing impairment while the other two
      had moderate hearing loss. CONCLUSIONS: The results of our study suggest that
      neurosensory hearing loss was found to be associated with renal agenesis. Further
      audiometric follow-up of children with renal agenesis seems worthwhile.

PMID- 11518588
TI  - Acoustic analysis of voice in children with noduli vocales.
AB  - The acoustic tests of voice were carried out on 46 children with noduli vocales
      before the treatment and after its completion. Acoustic parameters of voice were
      compared with the control group of children without voice pathology. The results
      of the investigation were analysed acoustically. It has been proved that jitter,
      shimmer, Fo tremor and HNR values significantly differentiate the children with
      noduli vocales from the children without pathological changes in the larynx.
      These parameters during treatment tend to approach normal values. Therefore, the
      acoustic analysis of voice may be used in treatment monitoring.

PMID- 11518589
TI  - Volunteer-based universal newborn hearing screening program.
AB  - OBJECTIVE: To evaluate efficacy and costs of a volunteer-based universal newborn
      hearing screening program. METHODS: The Lucile Packard Children's Hospital at
      Stanford newborn hearing screening program database was reviewed. Results and
      costs of the hearing screens were analyzed. RESULTS: Hearing screens were
      performed on 5771 newborns treated in the well-baby nursery and nine infants from
      this population were identified with hearing loss, seven of whom had no risks
      factors for hearing loss. Using volunteers to perform the first-line screen with
      the automated auditory brainstem response (AABR) technology, 91% of infants
      registered for screening were evaluated prior to discharge. An additional 4% of
      infants were screened as outpatients. If an infant failed the AABR on two
      occasions, he or she was rescreened with the AABR or transient evoked otoacoustic
      emissions by a licensed audiologist, often while the infant was still in the
      hospital. Using this algorithm, 5% of infants tested in the well-baby nursery
      needed additional follow-up as an outpatient. Cost analysis of this volunteer
      based program reveals a per/baby screening cost of $27.41. CONCLUSIONS: A
      volunteer-based hearing screening program is a viable option for hearing
      screening in well-baby nurseries but does not result in significant cost savings
      during the first 2 years of the program.

PMID- 11518590
TI  - Histological analysis of nasal polyps in children.
AB  - During 1991-1999, in the Children's ENT Department of Warsaw Medical University,
      39 polypectomies were performed. We analysed the histological structure of all
      polyps. The most common type of nasal polyp tissue in children was the
      inflammatory polyp (95% of cases).

PMID- 11518591
TI  - Fine needle aspiration biopsy of pediatric head and neck masses.
AB  - OBJECTIVE: To determine if fine needle aspiration (FNA) can preclude the
      requirement for diagnostic open biopsy in suspicious pediatric head and neck
      masses. METHODS: The records of 40 children presenting to an inner city tertiary
      care hospital who underwent a total of 50 FNA biopsies during the years 1988-1999
      were reviewed. From these 40 patients, 17 children, aged 3 months to 18 years,
      underwent both clinically indicated FNA biopsy and subsequent open surgical
      biopsy or excision. Outcome measurements included clinical resolution or surgical
      pathologic diagnosis. RESULTS: The 17 patients who underwent open surgical biopsy
      subsequent to the FNA had a total of 21 FNAs performed. Three of these patients
      had more than one needle biopsy prior to surgery. The histologic diagnosis of the
      surgical excision confirmed the FNA biopsy cytologic diagnosis in all but two
      cases. FNA cytologic diagnostic categories included reactive lymph node/non
      specific inflammation (25 biopsies), benign cystic process (four), granulomatous
      disease (eight), malignant neoplasm (three), and benign neoplasm (one). Eight of
      nine FNAs initially non-diagnostic had either complete resolution of the mass or
      a diagnosis obtained by subsequent FNA or open biopsy. CONCLUSIONS: FNA is a
      valuable diagnostic tool in the management of children with the clinical
      presentation of a suspicious neck mass. The technique reduces the need for more
      invasive and costly procedures. Early surgical biopsy, however, should be
      considered in rapidly enlarging masses, in the presence of persistent systemic
      symptoms, and when repeated FNA cytology is non-diagnostic.

PMID- 11518592
TI  - Malignant otitis externa in an infant with selective IgA deficiency: a case
      report.
AB  - The occurrence of malignant otitis externa (MOE) in infancy is rare. We report a
      case of MOE in a neonate who was later identified to have selective IgA
      deficiency. She was successfully treated with oral ciprofloxacin, but developed
      external auditory canal stenosis, a deformed pinna, persistent facial nerve
      palsy, temporal bone erosion and hearing loss. No cases of MOE in selective IgA
      deficiency have been reported in literature. This is also the first report on the
      use of ciprofloxacin in infants with MOE.

PMID- 11518593
TI  - Traumatic perilymphatic fistulas in children: etiology, diagnosis and management.
AB  - Post-traumatic perilymphatic fistulas have been described following ear and
      temporal bone injury, particularly in the setting of temporal bone fractures.
      However, indications for exploratory surgery in cases of trauma without temporal
      bone fracture are vague and not well described. We describe three children who
      presented with symptoms suggestive of perilymphatic fistula (PLF) without an
      associated temporal bone fracture: two with penetrating tympanic membrane
      injuries and one with blunt temporal bone trauma. All had symptoms of hearing
      loss and vestibular disturbance. Two of the children cooperated with ear-specific
      audiologic assessment, which demonstrated sensorineural hearing loss (SNHL) on
      the traumatized side. The third child showed audiometric evidence of a SNHL on
      the injured side, but due to his age, the degree of severity of the SNHL was
      unable to be appropriately addressed prior to the patient being surgically
      managed. All three children underwent exploratory surgery and were found to have
      bony defects in the region of the oval window. All were repaired with fascial
      grafts to the oval and round windows with complete resolution of vestibular
      symptoms. However, two of the three patients with documented post-operative
      audiograms suffered from persistent SNHL on the injured side. We conclude that
      exploratory middle ear surgery is indicated in patients suffering from blunt or
      penetrating temporal bone or middle ear trauma who demonstrate persistent
      vestibular symptoms, sensorineural hearing loss or radiographic evidence of oval
      window pathology. As this is a limited number of patients, a larger series may be
      warranted to study the actual incidence of post-traumatic PLF in the child with
      persistent hearing loss and vertigo after head or ear trauma.

PMID- 11518594
TI  - Primary pediatric neuroblastic tumors of the neck.
AB  - Neuroblastic tumors are the third most common cause of solid tumors in early
      childhood. Cervical tumors account for only 5% of cases. In this report, we
      describe a series of four pediatric neuroblastic tumors of the neck. The
      histological diagnosis was ganglioneuroblastoma in three cases and neuroblastoma
      in one case. Presenting signs were solitary cervical mass in two cases and
      respiratory distress in association with Claude-Bernard Horner's syndrome in two
      cases. Mean age at presentation was 15 months. Cervical computed tomography scan
      and/or magnetic resonance imaging depicted calcifications within the tumor in 50%
      of cases and allowed accurate assessment of extension. Increased urine
      catecholamine levels were observed only in the patient with neuroblastoma.
      Scintigraphy with [131]iodine-methyliodobenzylguanidine demonstrated selective
      uptake by the tumor in two cases. Amplification of N-myc oncogene, a documented
      unfavorable prognostic sign, was not found in any case. Surgical treatment was
      performed in all patients. Neoadjuvant chemotherapy was performed in one case.
      All patients underwent regular surveillance. No evidence of recurrence has been
      observed with a mean follow-up period of 7 years.

PMID- 11518595
TI  - The combined use of a Fogarty balloon with extraction forceps for the controlled
      retrieval of an endobronchial foreign body.
AB  - Foreign body aspiration is a common problem in children necessitating prompt
      recognition and early treatment to minimize the potentially serious and sometimes
      even fatal consequences. We report the case of a 7 year old girl with a peanut
      lodged in her right main bronchus. Bronchoscopy identified the foreign body which
      was then removed by the combined use of a Fogarty balloon catheter and extraction
      forceps. This case differs from previous reports, in that the foreign body and
      forceps were removed separately from the balloon catheter, which theoretically
      should minimize the risks associated with this procedure.

PMID- 11518596
TI  - Congenital nasal pyriform aperture stenosis: non-surgical management and long
      term analysis.
AB  - Congenital nasal pyriform aperture stenosis is a rare cause of airway obstruction
      in the newborn. Immediate recognition and therapy are essential for this
      potentially life-threatening condition. After initial management, which includes
      establishment of an oral airway, surgical repair of the stenotic bony inlet has
      been traditionally considered. We present a long-term follow-up of two patients
      with congenital pyriform aperture stenosis, who were managed expectantly.
      Pertinent embryology, clinical presentation, and general treatment strategies for
      these patients are also discussed.

PMID- 11518597
TI  - Hyalinizing trabecular adenoma versus papillary thyroid carcinoma in a child.
AB  - Hyalinizing trabecular adenoma (HTA) of the thyroid gland is a rare, benign
      neoplasm predominantly diagnosed in middle-aged women. There is mounting evidence
      in the medical literature, however, to suggest that HTA may represent an
      encapsulated variant of papillary thyroid carcinoma (PTC). This report describes
      an unusual case of PTC in a child initially diagnosed as HTA. Establishing an
      accurate diagnosis has important management implications for the pediatric
      patient.

PMID- 11518598
TI  - The relationship between per capita income and diffusion of medical technologies.
AB  - It is commonly known that per capita income is correlated with the level of
      health care spending and that technology is a major factor in explaining the
      increase in health care spending. This study examines differences in the rate of
      diffusion of medical technologies in Organization for Economic Cooperation and
      Development countries between 1975 and 1995. We find that the importance of
      income in explaining the long-term availability of a technology generally
      declines over time and becomes insignificant for some technologies. In other
      words, more affluent countries are earlier adopters of new technologies, but
      access to technology becomes less dependent on income over time. The evidence
      also suggests that the effects of reimbursement incentives are greater for
      purchases of diagnostic technologies than for lifesaving technologies and that
      reimbursement incentive effects are less significant for older technologies.

PMID- 11518599
TI  - Providing information on emerging health technologies to provincial decision
      makers: a pilot project.
AB  - A pilot project to provide advice on new and emerging medical technologies to
      decision makers in a provincial health care system was undertaken by a health
      technology assessment (HTA) program. Briefs were prepared on technologies which
      were not yet available in the province and which might have a significant impact
      on health care. These were sent to the ministry of health and regional health
      authorities and made available through the agency's website. Reaction to the
      briefs was sought from decision makers. Decision makers in the health ministry
      and health authorities found the briefs helpful, and wished to continue receiving
      them. They had made limited use of them for planning purposes, but the briefs
      provided useful input to further consideration of technologies in several cases.
      Within the HTA program, the briefs and the process that produced them were
      valuable in increasing awareness of new health technologies that might require
      assessment in future. This pilot project demonstrated the feasibility of
      providing timely advice on emerging health technologies within a provincial
      health system. However, while decision makers found the information provided to
      be useful, this had not yet been integrated with provincial health care planning.
      Necessary machinery within policy areas and communication with the HTA process
      appear to be in need of development.

PMID- 11518600
TI  - Application of strengths, weaknesses, opportunities and threats analysis in the
      development of a health technology assessment program.
AB  - There has been recent interest in developing a health technology assessment (HTA)
      function in Estonia. A group of individuals knowledgeable about HTA in Canada,
      Germany, Romania and Spain, along with representatives of the University of
      Tartu, Estonia, was convened by the Institute of Health Economics in Edmonton,
      Canada, to consider options for such a function. In a one-day workshop strengths,
      weaknesses, opportunities and threats (SWOT) analyses of HTA were conducted,
      first at a 'global' level, and then of the Estonian situation. The 'global' SWOT
      analysis yielded a large number of items that pertain to institutionalized HTA in
      a generic sense, i.e. not based on any individual HTA agency. The 'Estonian' SWOT
      yielded a subset of items, which pertain to development of HTA in that country.
      Ten actionable steps were then developed on the basis of this subset, which could
      be used to initiate the creation of an HTA body in Estonia.

PMID- 11518601
TI  - Strategies for promoting equity: experience with community financing in three
      African countries.
AB  - Although the need for a pro-poor health reform agenda in low and middle income
      countries is increasingly clear, implementing such policy change is always
      difficult. This paper seeks to contribute to thinking about how to take forward
      such an agenda by reflection on the community financing activities of the
      UNICEF/WHO Bamako Initiative. It presents findings from a three-country study,
      undertaken in Benin, Kenya and Zambia in 1994/95, which was initiated in order to
      better understand the nature of the equity impact of community financing
      activities as well as the factors underlying this impact. The sustained relative
      affordability gains achieved in Benin emphasise the importance of ensuring that
      financing change is used as a policy lever for strengthening health service
      management in support of quality of care improvements. All countries, however,
      failed in protecting the most poor from the burden of payment, benefiting this
      group preferentially and ensuring that their views were heard in decision-making.
      Tackling these problems requires, amongst other things, an appropriate balance
      between central and local-level decision-making as well as the creation of local
      decision-making structures which have representation from civil society groups
      that can voice the needs of the most poor. Leadership, strategy and tactics are
      also always important in securing any kind of equity gain-such as establishing
      equity goals to drive implementation. In the experiences examined, the dominance
      of the goal of financial sustainability contributed to their equity failures.
      Further research is required to understand what equity goals communities
      themselves would prefer to guide financing policy.

PMID- 11518602
TI  - Fear and social isolation as consequences of tuberculosis in VietNam: a gender
      analysis.
AB  - SETTING: The study was conducted in four districts in different regions of
      Vietnam. OBJECTIVE: To describe the socio-economic consequences of tuberculosis
      (TB) in Vietnam with special reference to gender differentials concerning social
      stigma and isolation. DESIGN: Sixteen focus group discussions were carried out
      with men and women, TB patients and non-TB participants. Data was analysed using
      modified grounded theory technique. RESULTS: Generally, the participants had good
      knowledge about TB. However, knowledge and practice were not closely related in
      the sense that most non-TB participants perceived that TB can be successfully
      cured, while patients were seriously shocked when they were told that they had
      TB. Male patients often worried about economic-related problems, while female
      patients worried about social consequences of the disease. Both in the family and
      the community, isolation could be subtle, but it could also be obvious and had a
      tendency to continue much longer than medically justified. CONCLUSION:
      Information on stigma and isolation due to TB and gender differences is important
      for understanding patient dynamics and its effects on the disease. Tuberculosis
      control programmes need better understanding of the gender differences in
      attitudes and beliefs to improve case-detection and treatment outcome.

PMID- 11518603
TI  - Policy implications of the inadequate support systems for orphans in western
      Kenya.
AB  - This paper describes the support systems available for orphans in a rural Luo
      community in Nyang'oma sub-location in Bondo District of Western Kenya.
      Qualitative data were collected through in-depth interviews with orphaned
      children and their caretakers as well as key informants, and through focus group
      discussions with orphaned children, widows and community elders. Quantitative
      data were obtained by questionnaires administered to 100 caretakers of orphaned
      children. The most serious problem was inability of the orphan households to
      afford school fees, although lack of food, medicare and clothing were also
      prominent. The traditional, kinship-based support systems made a major
      contribution to catering for the orphans though the resources were far from
      enough. Various community-based groups in the area did not contribute
      significantly. The problem is getting desperate due to a combination of an
      exponentially increasing prevalence of orphans, poor socio-economic conditions
      and decline of the traditional support systems. For health planners and policy
      makers there are two major concerns. In the short term, a big and rapidly growing
      group of children are without adequate access to health services, while in the
      long term, the negative consequences for (in particular the girl) orphans'
      schooling pose a serious threat to the health of their future children. Based on
      the study findings, two recommendations are made: that the responsible parties
      address the issue of education for orphans rapidly and sufficiently and with due
      consideration of their food security and medicare; and that potential community
      resources such as kinship networks and community groups are mobilised in order to
      assist in achieving the goal.

PMID- 11518605
TI  - Mechanisms of chemical carcinogenesis and application to human cancer risk
      assessment.
AB  - The distinction between DNA-reactive and epigenetic carcinogens and their roles
      in oncogenesis is reviewed. An approach to cancer hazard assessment based upon
      mechanisms is described.

PMID- 11518606
TI  - Classification of carcinogenic chemicals in the work area by the German MAK
      Commission: current examples for the new categories.
AB  - The German Commission for the Investigation of Health Hazards of Chemical
      Compounds in the Work Area (MAK Commission) introduced an extended classification
      scheme in 1998. In addition to the traditional three categories still used to
      date, now called: Category 1 (human carcinogen); Category 2 (animal carcinogen);
      and Category 3 (suspected carcinogen), two new Categories (4 and 5) were added.
      Classification of substances into the new Categories 4 and 5 is based on the
      knowledge of mode of action and the potency of carcinogens. The essential feature
      of substances classified in the new Categories 4 and 5 is that exposure to these
      chemicals does not contribute significantly to the risk of cancer to man,
      provided that an appropriate exposure limit (MAK value) is observed. Chemicals
      known to act typically by non-genotoxic mechanisms are classified in Category 4.
      Genotoxic chemicals for which low carcinogenic potency can be assessed on the
      basis of dose-response relationships and toxicokinetics are classified in
      Category 5. Since the use of this scheme for 3 years, various chemicals have been
      classified in one of the new categories. However, in several cases data to
      sufficiently substantiate a MAK value are missing. Such substances are now
      classified in a subcategory of Category 3, called Category 3 A, which indicates
      that further data are required for final classification. Examples are given for
      classification of dichloromethane into Category 3 A, chloroform and sulfuric acid
      into Category 4 and ethanol into Category 5.

PMID- 11518607
TI  - Cell transformation in vitro by food-derived heterocyclic amines Trp-P-1, Trp-P-2
      and N(2)-OH-PhIP.
AB  - Heterocyclic aromatic amines (HCA) are formed upon frying of poultry, fish or
      meat and have been shown to induce tumours in rodent bioassays. We investigated
      the transforming activity of HCA in an in vitro assay using the M2/C3H mouse
      fibroblast cell line. An external metabolic activation system (rat liver
      homogenate) was required in order to observe any HCA-induced cytotoxic effects or
      cell transforming activity. Trp-P-1 and Trp-P-2 are shown to be among the most
      potent transforming HCA that have been detected in food. Metabolic activation of
      HCA has been shown to proceed via N-hydroxylation of the exocyclic amino group.
      Therefore, we tested 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine (N(2)
      OH-PhIP) the activated metabolite of 2-amino-1-methyl-6-phenylimidazo[4,5
      b]pyridine. N(2)-OH-PhIP proved to be one of the most powerful compounds with
      transforming activity observable at a concentration as low as 30 nM. Since 2
      amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is the most abundant HCA
      formed in fried and grilled food and N-hydroxylation appears to be the
      predominant pathway of human metabolism, these data support the hypothesis that
      HCA are involved in the aetiology of human cancer.

PMID- 11518608
TI  - New DNA adducts of crotonaldehyde and acetaldehyde.
AB  - This paper summarizes our recent studies on adducts produced in the reactions of
      the carcinogens crotonaldehyde (2-butenal) and acetaldehyde with deoxyguanosine
      (dG) and DNA. Human exposure to these carcinogens can be considerable, from both
      exogenous and endogenous sources. Crotonaldehyde reacts with DNA to form Michael
      addition products, a pathway that has been well described. We describe a second
      major pathway, in which 3-hydroxybutanal, formed by addition of H(2)O to
      crotonaldehyde, reacts with DNA to produce the Schiff base N(2)-(3-hydroxybut-1
      ylidene)dG as well as several diastereomers of N(2)-paraldol-dG. Acetaldehyde
      reacts with DNA and dG giving a major Schiff base adduct, N(2)-ethylidene-dG. A
      cross-linked adduct of acetaldehyde has been characterized for the first time,
      and other adducts resulting from the reaction of two and three molecules of
      acetaldehyde with dG have been observed. The results of these studies demonstrate
      that some structurally unique adducts are formed from these carcinogenic
      aldehydes and suggest some new directions for research on the potential role of
      aldehydes in human cancer.

PMID- 11518609
TI  - From carcinogenesis to clinical interventions for cancer prevention.
AB  - During the last three decades, the scientific community has made immense progress
      in acquiring the knowledge needed to prevent cancer. Pioneering research helped
      to identify potential causes of cancer, particularly environmental factors such
      as diet, and provided insight regarding their mechanisms-of-action. Concurrently,
      promising inhibitors of cancer that appeared able to either arrest or reverse
      cancer development by interfering with one or more steps in the process of
      carcinogenesis were identified and systematically evaluated for their potential
      as chemopreventive agents. Numerous agents determined to be safe and effective in
      preclinical trials have been and continue to be tested in Phase I,II, and III
      clinical interventions for cancers at various sites, including breast, colon,
      prostate, esophagus, mouth, lung, cervix, endometrium, ovary, liver, bladder, and
      skin. The development of valid intermediate biomarkers that can serve as
      surrogate endpoints for clinical disease is urgently needed to accelerate
      advances in clinical trials for cancer prevention.

PMID- 11518610
TI  - Smoking cessation in cancer prevention.
AB  - Tobacco smoking is the largest preventable risk factor for morbidity and
      mortality in industrialized countries. WHO estimates that tobacco will become the
      largest single health problem by 2020, causing an estimated 8.4 million deaths
      annually. Tobacco has central importance in the etiology of cancers of the lung,
      head and neck, urinary tract, and pancreas. Reducing the number of young people
      who take up smoking and helping those who have started to smoke to quit the habit
      are the key ways of preventing these cancers. Tobacco- or nicotine-dependence is
      a common, chronic, relapsing medical condition. Studies of twins have implicated
      genetic factors in most of the differences in vulnerability to tobacco smoke and
      in the persistence of the smoking phenotype. The available interventions for
      reducing tobacco use and treatment for nicotine dependence offer public health
      officials and clinicians the greatest single opportunity for disease prevention.
      Five medications -- nicotine chewing gum, nicotine patches, nicotine inhalers,
      nicotine nasal sprays and bupropion -- and behavioural therapy appear to be both
      effective and safe: they double the quitting rates and are associated with a
      dropout rate due to adverse events of less than 5%.

PMID- 11518611
TI  - Suppressive effect of irsogladine maleate on N-methyl-N-nitro-N-nitrosoguanidine
      (MNNG)-initiated and glyoxal-promoted gastric carcinogenesis in rats.
AB  - The modifying effect of irsogladine maleate (IRG) on N-methyl-N-nitro-N
      nitrosoguanidine (MNNG)-initiated and glyoxal-promoted gastric carcinogenesis was
      examined in male Wistar rats. Six-week-old rats were divided into ten groups.
      Groups 1 through 6 were given MNNG (100 mg/l in drinking water) for 25 weeks from
      the start of the experiment, whereas groups 7 through 10 received distilled water
      in the initiation phase as the vehicle treatment. Groups 1 and 8 were kept on the
      basal diet and distilled water throughout the experiment (55 weeks). Groups 2-8
      were given 0.5% glyoxal in the drinking water for 30 weeks from 26th week of the
      experiment. Group 3 was fed the diet mixed with 100 ppm IRG for 25 weeks from the
      start of experiment. Groups 4 and 8 were fed the diet mixed with 100 ppm IRG for
      30 weeks from 26th week of experiment. Groups 5 and 9 or 6 were given 100 or 25
      ppm IRG containing diet, respectively throughout the experiment. Group 10 was
      given the basal diet and distilled water as the vehicle treated control. Tumors
      of upper digestive tracts (stomach and duodenum) were developed in groups: 1
      (12/17 rats, 71%), 2 (11/12 rats, 92%), 3 (9/16 rats, 56%), 4 (5/12 rats, 42%), 5
      (6/15 rats, 40%) and 6 (7/12 rats, 58%). High dose of IRG in initiation and/or
      promotion phase significantly reduced the incidence of tumors of the upper
      digestive tracts. The average numbers of the digestive tracts neoplasms in groups
      3,5 and 6 given glyoxal and IRG were less than those in group 2 which received
      only glyoxal. These results suggest that IRG could be a preventive agent against
      the occurrence of neoplasms of the upper digestive tract.

PMID- 11518612
TI  - Comparison of the antioxidant content of fruits, vegetables and teas measured as
      vitamin C equivalents.
AB  - Most of the health benefits of black, green and oolong teas made from Camellia
      sinensis are attributed to their antioxidant content. Many plants and spices have
      been used to make infusions that are erroneously referred to as 'teas'. The term
      'rich in antioxidants' is often used to describe such infusions, often without
      scientific support. We have used the DPPH method to quantify the total radical
      scavenging capacity (RSC) of a wide range of 'teas', fruits and vegetables. The
      results are presented as vitamin C equivalents. These results are compared to the
      RSC of the recommended portions of fruits and vegetables in the food guide
      pyramid for a healthy and balanced diet. The EC(50) results show that there are
      no statistically significant differences in the RSC of black, green and oolong
      teas. However, the RSC of 'teas' made from other species of plants are
      significantly lower. Our results show that one or two cups of tea would provide a
      similar amount of RSC as five potions of fruits and vegetables or 400 mg vitamin
      C equivalents. This would be comparable to two capsules (200 mg) of vitamin C.
      Caution is advised in extrapolating these in vitro results to humans due to
      bioavailability.

PMID- 11518613
TI  - Toxicological profile of pollutants in surface water from an area in Taihu Lake,
      Yangtze Delta.
AB  - The environment in urbanized areas is often contaminated with a complex mixture
      of toxic compounds originating from industries, agriculture and private
      households. Most of the contaminants end up in surface waters, such as lakes,
      rivers and finally the sea. Toxic contaminants may disturb the biological
      condition of aquatic ecosystems and be harmful for humans, if they are
      transported to human food or drinking water. A variety of biological tests have
      been introduced for monitoring the toxicological profile of aquatic ecosystems.
      In the present investigation, genotoxic, hormone disrupting and Ah-receptor
      activity was analyzed in water collected in January 1999 at Meiliang Bay, Taihu
      Lake, China, near to the city of Wuxi in the Shanghai area. Significant mutagenic
      activity could be detected in water extracts with the Salmonella/microsome assay
      and the arabinose resistance test. Frame shift mutations were the predominant
      mode of action. Ah-receptor active compounds were detected by using a luciferase
      reporter gene assay (CALUX-assay). The estimated toxic equivalent factor-values
      ranged between 134 and 232 pg TCCD-equivalents per liter lake water. The estrogen
      like potential of Taihu water was estimated with two luciferase reporter gene
      assays using transgenic human cell lines expressing estrogen receptor alpha.
      Estradiol equivalents obtained with water extracts were in the range of 2.2-12.1
      ng/l. We also analyzed the concentrations of 17-beta-estradiol and
      ethinylestradiol in the extracts using a high-pressure liquid chromatography
      method. The values obtained correlated with the biologically determined estradiol
      equivalents, indicating that the estrogenic activity is mainly due to natural and
      synthetic hormones rather than xenoestrogens.

PMID- 11518614
TI  - Comparison of an array of in vitro assays for the assessment of the estrogenic
      potential of natural and synthetic estrogens, phytoestrogens and xenoestrogens.
AB  - Many chemicals in surface waters and sediments have recently been discovered to
      have estrogenic/antiestrogenic activity. Among these compounds, known as
      'endocrine disrupters', are natural and synthetic hormones, phytoestrogenes and a
      variety of industrial chemicals, such as certain detergents and pesticides. These
      substances are supposed to affect the development and reproduction in wildlife
      and humans and may also be involved in the induction of cancer. In order to
      assess the estrogenic/antiestrogenic potential of pure compounds and complex
      environmental samples we compared an array of in vitro test systems, (i) two
      luciferase reporter gene assays using transgenic human MVLN cells (derived from
      MCF-7 cells) and HGELN cells (derived from HeLa cells); (ii) a competitive
      binding assay with recombinant human estrogen receptors (ER) alpha and beta; and
      (iii) a proliferation assay with MCF7-cells (E-Screen). The sensitivity of the
      assays for 17-beta-estradiol decreased in the order: MVLN-cells=E-Screen>HGELN
      cells>binding to ER-alpha>binding to ER-beta. A good correlation was obtained
      between the estrogenic potencies of 11 compounds (17-beta-estradiol (E(2)),
      estrone (E(1)), estriol (E(3)), ethinylestradiol (EE(2)), diethylstilbestrol
      (DES), coumestrol, beta-sitosterol, genistein, 4-nonylphenol, 4-octylphenol,
      bisphenol A) in the three tissue culture assays. The relative potencies of the
      compounds obtained by the cell free binding assays were one to two orders of
      magnitude higher compared with the cell culture assays. The phytoestrogens showed
      a preference to bind to ER-beta, but only genistein showed a much lower activity
      in the E-Screen (growth induction in breast cancer cells) compared with the
      luciferase induction in MVLN and HGELN-cells.

PMID- 11518615
TI  - Development of an allergy test model: activation of human mast cells with
      potentially allergenic substances.
AB  - Due to the permanent increase of newly developed and already existing allergies,
      simple, quick, and reliable test models for detecting potentially allergenic
      substances are still required. Here, we describe the development of a new in
      vitro allergy test based on isolated primary mast cells (MC) of non-allergic
      patients from lung tissue and foreskin specimens, respectively. To establish the
      specificity of the test model we used primary MC stimulated with immunoglobulin E
      (IgE), human recombinant stem cell factor (hrSCF), and anti-IgE antibodies to
      release significant amounts of histamine indicating the ability of MC to cause a
      hypersensitivity reaction of the immediate type. The general applicability of
      this test model for detecting allergenic substances could be confirmed by
      histamine release of primary MC stimulated with sera of patients suffering from
      house dust allergy, and the corresponding antigen Dermatophagoides pteronyssinus.
      The results of the present work suggest that this newly developed human in vitro
      model provides the opportunity of testing substances for their allergenic
      potential within days and at low costs. This could also be of particular interest
      for newly produced compounds.

PMID- 11518616
TI  - Towards in-vitro prediction of an in-vivo cytostatic response of human tumor
      cells with a fast chemosensitivity assay.
AB  - The objective of this study is to evaluate a novel approach to chemosensitivity
      testing with respect to its predictive value in the selection of clinically
      effective cytostatic drugs to optimize the therapeutic treatment of cancer. The
      chemosensitivity assay, which we used in this study, has its roots in
      pharmaceutical drug screening and the surrounding intellectual property is
      protected by various patent applications and trademarks. Therefore, we will refer
      to this test in the following pages as ChemoSelect. ChemoSelect is a sensor-chip
      based diagnostic test, which permits the functional and continuous real-time
      measurement of induced tumor cell cytotoxicity following the administration of
      chemotherapeutic drugs. Chemosensitivity is measured through the reduction of the
      excretion of lactic and carbonic acids--by-products of the metabolic processes of
      glycolysis and respiration and a parameter for cell vitality--generated
      specifically by ATP hydrolysis and lactic acid production. We used this test to
      study the applicability of this assay for tumor cells based on the analysis of
      tumor cell lines and tumor specimens. In this preliminary study, this test was
      studied in predicting chemoresistance and chemosensitivity in cell lines and
      tumor specimens for which the result was already predetermined by the properties
      of the cell line or the tumor specimen used in the experiment. The applicability
      in a clinical setting was studied by confirming the trends on selected drug
      sensitivity and drug resistance with an interim analysis of an ongoing clinical
      study in selected patients with breast cancer undergoing neoadjuvant
      chemotherapy. The minimum detection limit of cells and biologic cell responses,
      an important variable determining the applicability of the test in routine
      clinical use, was also assessed. ChemoSelect avoids many of the limitations of
      existing chemoresistance assays and provides more comprehensive information and
      output, as it has a 24-h turnaround time, is applicable to the majority of solid
      tumors and available cytostatic drugs, does not need more than 10(5) cells in
      total, cultivated tumor cells, provides dynamic monitoring of cellular responses
      through on-line data read-out during the perfusion with drugs and can be extended
      to the analysis of novel therapeutic modalities such as biologics.

PMID- 11518617
TI  - Abstracts of EUROTOX 2001. 13-16 September 2001. Istanbul, Turkey.

PMID- 11518618
TI  - Nitric oxide synthase expression and nitric oxide/cyclic GMP pathway in swine
      granulosa cells.
AB  - The present investigation was undertaken to verify if the two nitric oxide
      synthase isoforms, eNOS and iNOS, are present in swine granulosa cells and
      whether the enzyme soluble guanylate cyclase is functionally active in the same
      cells and can account for NO effects. Using western blotting, the presence of
      endothelial NO synthase was demonstrated in freshly collected cells; on the
      contrary, iNOS expression was not observed in the same cells either before or
      after culture with the inflammatory cytokine hTNF-alpha. The treatment with a
      strong NO donor (S-Nitroso-L-acetyl penicillamine, SNAP) determined an increase
      of cGMP levels in culture media, which was attenuated by the combined treatment
      with an inhibitor of NO-sensitive soluble guanylate cyclase, 1H
      [1,2,3]oxadiaziolo [4,3a]quinoxaline -1-one (ODQ). The cGMP analog, 8 bromo-cGMP,
      mimicked the strong inhibitory effect exerted by SNAP on estradiol 17 beta and
      progesterone production, while ODQ did not modify steroids concentrations in
      culture media. These observations demonstrate the presence of a follicular NO
      generating system, which in swine granulosa cells seems to include only the
      endothelial NOS isoform. Furthermore, the nitric oxide/cyclic GMP system seems to
      be functionally active in these cells, since cGMP appears to mediate NO action,
      even if it cannot account completely for NO inhibitory effect on steroidogenesis.

PMID- 11518619
TI  - Characterization of uterine epidermal growth factor during early pregnancy in
      pigs.
AB  - Genomic research has identified a quantitative trait locus for uterine capacity,
      a component trait contributing to litter size, on porcine chromosome 8. The
      epidermal growth factor (EGF) gene, on porcine chromosome 8, may influence
      uterine capacity because of its growth-promoting activities. Using reverse
      transcription-polymerase chain reaction (PCR) and iterative screening of a
      porcine reproductive tissue cDNA library, 4932 bp cDNA sequence coding for
      porcine EGF precursor was obtained. The predicted protein sequence of the EGF
      precursor contained 1214 amino acids, similar to human EGF precursor (1207 amino
      acids, 81% identity). Curiously, the sequence of the mature peptide was less
      homologous between species than other regions of EGF precursor. The presence of
      conserved regions outside the mature peptide may suggest that these regions are
      functionally important. Expression of EGF mRNA in the endometrium of White
      crossbred gilts (n = 3 to 5 each) was determined by Northern blotting using 20
      microg of total RNA from endometrium of D 10, 13, and 15 cyclic, and D 10, 13,
      15, 20, 30, and 40 of pregnant gilts. A 3342 bp probe from EGF precursor was
      used. The bands corresponding to EGF mRNA were quantified by densitometry and
      results were analyzed by ANOVA. EGF mRNA expression decreased significantly from
      D 13 to 15 of the cycle and pregnancy (P = 0.04), and from D 30 to 40 of
      pregnancy (P = 0.01). These findings show that EGF mRNA expression is temporally
      regulated during the cycle and early pregnancy, and this pattern of gene
      expression may be important during early conceptus development.

PMID- 11518620
TI  - Endotoxin induces delayed ovulation following endocrine aberration during the
      proestrous phase in Holstein heifers.
AB  - The effect of endotoxin on follicular growth and on secretion of LH, estradiol
      17beta, progesterone and cortisol during the proestrous phase in cattle was
      investigated. Holstein heifers were treated with PGF2alpha at 11-13 d after
      ovulation to induce luteolysis. At 42 hr after PGF2alpha treatment, heifers were
      administered either lipopolysaccharide (LPS; Escherichia coli, O111:B4, 5
      microg/kg, n = 6) or saline (control; n = 6) by i.v. bolus injection. Ovarian
      structures were monitored daily by transrectal ultrasonography, and blood samples
      were collected at various times for hormonal analysis. The duration from
      PGF2alpha treatment to ovulation was significantly longer in the LPS group (8.0
      +/- 1.3 d) than in the control group (4.2 +/- 0.2 d). LPS significantly reduced
      the pulse frequency of LH for 6 hr after the administration, and increased the
      mean concentration and pulse amplitude of LH from 3 to 6 hr after the
      administration. The plasma concentrations of progesterone and cortisol were
      transiently increased after LPS administration. The plasma concentration of
      estradiol-17beta was significantly decreased at 24 hr after LPS administration
      compared to that in the controls. Five of six LPS-treated heifers exhibited no
      preovulatory LH surge until 120 hr after PGF2alpha treatment and the remaining
      heifer exhibited the surge at 108 hr after PGF2alpha treatment, while the LH
      surge was observed at 54-78 hr after PGF2alpha treatment in control heifers.
      These results suggest that endotoxin disrupts progression of the proestrous phase
      of cattle, interrupting the preovulatory estradiol rise and thus delaying the LH
      surge and the subsequent ovulation.

PMID- 11518621
TI  - Lamprey gonadotropin-releasing hormone-III selectively releases follicle
      stimulating hormone in the bovine.
AB  - Recent studies have shown that lamprey gonadotropin-releasing hormone (l-GnRH) is
      localized in the mammalian brain, and that l-GnRH-III, can selectively induce FSH
      secretion in the rat both in vivo and in vitro. Consequently, the purpose of this
      study was to determine if l-GnRH-III could elicit selective FSH release in cattle
      and compare this response with that to mammalian luteinizing hormone releasing
      hormone (m-LHRH). Cattle were chosen as the animal model because previous studies
      have demonstrated that FSH and LH are secreted by separate gonadotropes in that
      species. For these studies, crossbred cycling heifers were implanted with jugular
      cannulae and l-GnRH-III was infused either between Days 9-14 or on Day 20 of the
      estrous cycle. Blood samples were collected both before and following peptide
      infusion. Our results demonstrate that during Days 9-14 of the estrous cycle
      (luteal phase), when progesterone levels averaged between 4 and 5 ng/ml, a dose
      of 0.25 mg of l-GnRH-III induced the release of FSH (P < 0.05), but not LH. A 0.5
      mg dose of l-GnRH-III caused a greater release of FSH (P < 0.01), but still did
      not induce LH release. Higher doses of the peptide were capable of significantly
      releasing both gonadotropins. Importantly, during the luteal phase, doses of 0.5
      and 2 mg of m-LHRH were ineffective in stimulating FSH, but did elicit marked
      increases (P < 0.001) in LH. Again, progesterone levels averaged 4-5 pg/ml. In
      order to assess gonadotropin releasing ability of l-GnRH-III at a different phase
      of the estrous cycle, some animals were administered the peptide on Day 20, when
      progesterone levels were below 1.0 pg/ml. At this time, the l-GnRH-III induced
      the release of LH (P < 0.01), but not FSH. Overall, our results demonstrate that
      l-GnRH-III can selectively induce FSH in cattle during the luteal phase, whereas
      m-LHRH was ineffective in that regard. Furthermore, the fact that l-GnRH-III can
      selectively stimulate FSH when serum progesterone is high, and LH when serum
      progesterone is low, suggests its actions are under strong control of this
      steroid. We suggest the FSH releasing capacity of l-GnRH-III in cattle could
      render this peptide useful for enhancement of reproductive efficiency in this
      species.

PMID- 11518622
TI  - Behavioral and metabolic features of repetitive seizures in immature and mature
      rats.
AB  - Seizure incidence varies significantly with age, with seizure susceptibility
      particularly high during the first few years of life. Of significant concern is
      what effects do brief, repetitive seizures have on the developing brain. We
      approached this issue by examining the change in seizure threshold, and related
      markers of neuronal activity and metabolic activity (c-fos mRNA and 2
      deoxyglucose [2DG]), as a function of repetitive seizure episodes in immature and
      mature rats. Starting on postnatal day 15 (P15) (immature) or P60 (adult) rats
      were given two flurothyl seizures a day for 5 days (nine or ten seizures). The
      seizure latency profile, our measure of threshold, in immature versus adult rats
      across the 5-day testing period was different. In immature rats, threshold for
      the second seizure on each day was significantly lower than for the first
      seizure, suggesting that there was little refractoriness after the first seizure
      of the day. In contrast, the mature animal had a significantly longer threshold
      latency to the second seizure for the first 3 days of testing. The immature
      animal was also more likely than the adult to exhibit tonic extension as a
      feature of the first seizure of the day. Following repetitive seizures, more
      regions of the CNS showed c-fos mRNA expression in the immature animal than
      adults, suggesting that repetitive seizures in the immature animal activated a
      greater percentage of the brain. Compared with the effects of a single seizure,
      repetitive seizures resulted in less 2DG labeling in most regions of the brain
      (except the hippocampus); in the immature brain this difference was more distinct
      than in adults. The consequences of repetitive seizures in the immature animal
      results in distinctly different seizure behavior and neuronal activity pattern (c
      fos expression) than that observed in the mature animal.

PMID- 11518623
TI  - Effect of lamotrigine treatment on status epilepticus-induced neuronal damage and
      memory impairment in rat.
AB  - Status epilepticus causes neuronal damage that is associated with cognitive
      impairment. The present study examined whether a novel antiepileptic drug,
      lamotrigine (LTG), alleviates status epilepticus-induced temporal lobe damage and
      memory impairment, and compared its efficacy with carbamazepine. Status
      epilepticus was induced by electric stimulation of the perforant pathway (PP) in
      rats. Treatment with LTG (12.5 mg/kg, twice a day) was started either 3 days
      before (preLTG group) or 1 h after (postLTG group) a 60 min PP stimulation.
      Treatment with carbamazepine (CBZ; 30 mg/kg, twice a day) was started 3 days
      before (CBZ group) a 60 min PP stimulation. All treatments were continued for 2
      weeks. Thereafter, the severity of seizures, seizure-induced neuronal damage,
      quantitative electroencephalogram (EEG), and memory impairment were compared
      between vehicle-treated unstimulated and stimulated controls, LTG-treated rats,
      and CBZ-pretreated rats. Both in the preLTG and postLTG groups, damage to hilar
      somatostatin-immunoreactive neurons, hippocampal CA3b and CA3a pyramidal cells,
      and the piriform cortex was mild and did not differ from that in unstimulated
      controls. Furthermore, CA3c damage in the preLTG group did not differ from that
      in unstimulated controls. Vehicle-treated stimulated controls and CBZ-pretreated
      rats, however, had significant damage in the hilus, CA3 subregions, and piriform
      cortex compared with unstimulated controls (P<0.05 for the stimulated side,
      contralateral side, or both). Treatment with LTG or CBZ had no effect on the
      number or duration of behavioral seizures during PP stimulation. They did not
      affect the baseline EEG or status epilepticus-induced slowing of the EEG. Also,
      the status epilepticus-induced spatial memory impairment in the Morris water-maze
      was not attenuated by treatment with LTG or CBZ. Our data demonstrate that
      treatment with LTG has a mild neuroprotective effect on status epilepticus
      induced neuronal damage in rats even when administered after the beginning of
      status epilepticus.

PMID- 11518624
TI  - The ovarian hormones and absence epilepsy: a long-term EEG study and
      pharmacological effects in a genetic absence epilepsy model.
AB  - In the first experiment, the relationship between the phase of the estrous cycle
      and the number of spontaneously occurring spike-wave discharges was investigated
      in WAG/Rij rats, a model for generalized absence epilepsy. The
      electroencephalogram (EEG) was continuously recorded for 96 h in eight rats
      chronically equipped with cortical EEG electrodes. A circadian pattern emerged
      for the number of spike-wave discharges: a nadir during the first hours of the
      light period, and an acrophase during the first hours of the dark period. This
      daily maximum was increased at proestrus day compared with the other days of the
      cycle, when the plasma level of progesterone is enhanced specifically at these
      hours of this day. This suggests that progesterone enhances spike-wave
      discharges. There was no difference in the first few hours of the light period in
      the number of spike-wave discharges between proestrus and the three other days,
      suggesting that estradiol has no effect on spike-wave discharges. In the second
      study, the effects of the systemic administration of progesterone and 17 beta
      estradiol on spike-wave discharges and spontaneous behavior were investigated. It
      was shown that progesterone (20 and 30 mg/kg) but not estradiol (0.17-1.5 mg/kg)
      increased the number and total duration of spike-wave discharges. On the other
      hand, injection of RU 38486 (10 and 30 mg/kg), an antagonist of intracellular
      progesterone receptors, had no effect on spike-wave discharges and did not block
      the stimulatory effect of progesterone. The antagonist of 17 beta-estradiol
      tamoxifen (1 and 3 mg/kg) did not evoke alterations in the number or duration of
      spike-wave discharges. Our results indicate that progesterone aggravates spike
      wave discharges, but is not mediated through intracellular receptors. Since
      progesterone is rapidly metabolized in the brain to the positive modulator of
      GABA(A) receptor allopregnanolone, which increases spike-wave discharges in
      WAG/Rij rats, it is possible that the epileptiformic effects of progesterone are
      mediated through this metabolite.

PMID- 11518625
TI  - Sleep in Lennox-Gastaut syndrome: the role of the cyclic alternating pattern
      (CAP) in the gate control of clinical seizures and generalized polyspikes.
AB  - Non-rapid eye movement (NREM) sleep contains periods of arousal instability
      (cyclic alternating pattern or CAP) and periods of arousal stability (non-CAP).
      During CAP, arousal oscillates between higher (phase A) and lower (phase B)
      levels of activation. We evaluated the relationship between CAP and the
      occurrence of epileptic events, i.e. clinical seizures and generalized interictal
      discharges, during sleep in 10 patients with Lennox-Gastaut syndrome (LGS). The
      macro- and microstructure of sleep of 10 attended overnight polysomnograms were
      analyzed. Compared with 10 age- and gender-matched controls, patients with LGS
      had significantly less stage 2 and REM sleep and higher amounts of CAP rate (68%
      vs. 33%; P<0.0001). The number of generalized polyspike bursts per hour of sleep
      was highest in slow wave sleep (226.5+/-57.6) and lowest in REM sleep (3.9+/
      1.5). The polyspike burst frequency was significantly greater (P<0.017) during
      CAP (213.2+/-60.1) than during non-CAP (100.3+/-40), and within CAP, generalized
      polyspikes occurred more often (P=0.005) during phase A (461.1+/-127.2) than
      during phase B (6.1+/-1.9). The total amount of generalized polyspike bursts
      identified in NREM sleep correlated positively both with the number of A phases
      containing at least one generalized polyspike (P=0.005) and with the mean number
      of polyspikes within each of these A phases (P<0.0001). Nocturnal clinical
      seizures occurred in 8 of the 10 patients and showed a similar trend. We conclude
      from our results that CAP modulates the occurrence of both clinical seizures and
      generalized epileptic discharges in LGS by means of a gate-control mechanism: an
      independent spike generator is inhibited in phase B and non-CAP and bursts with
      its intrinsic activity in phase A.

PMID- 11518626
TI  - Systematic review of the role of prostaglandins and their synthetase inhibitors
      with respect to febrile seizures.

PMID- 11518627
TI  - Levetiracetam, oxcarbazepine, remacemide and zonisamide for drug resistant
      localization-related epilepsy: a systematic review.
AB  - OBJECTIVE: To undertake a systematic review and meta-analysis of placebo
      controlled add-on trials of levetiracetam, oxcarbazepine, remacemide and
      zonisamide for patients with drug resistant localization related epilepsy.
      METHODS: We searched Medline, The Cochrane Library and contacted the relevant
      pharmaceutical companies. Outcomes were 50% or greater reduction in seizure
      frequency and treatment withdrawal for any reason. Data were synthesised in a
      meta-analysis. The effect of dose was explored in regression models for
      levetiracetam and remacemide. RESULTS: We found four trials (1023 patients) of
      levetiracetam, two (961) of oxcarbazepine, two (388) of remacemide and three
      (499) of zonisamide. Ignoring dose, the relative risks (95% CI) for a 50%
      response were 3.78 (2.62-5.44), 2.51 (1.88-3.33), 1.59 (0.91-2.97) and 2.46 (1.61
      3.79), respectively. There was evidence for increasing effect with increasing
      dose for levetiracetam, oxcarbazepine and remacemide. The relative risks for
      treatment withdrawal were 1.21 (0.88-1.66), 1.72 (1.35-2.18), 1.90 (1.00-3.60)
      and 1.64 (1.02-2.62), respectively. CONCLUSIONS: These data suggest a useful
      effect for levetiracetam, oxcarbazepine and zonisamide. Levetiracetam has the
      more favourable 'responder-withdrawal ratio' followed by zonisamide and
      oxcarbazepine.

PMID- 11518628
TI  - Topiramate on ictal seizure semiology: a quantitative, randomized, low and medium
      dose-controlled study.
AB  - OBJECTIVE: Intensive and quantitative evaluation of the severity and frequency of
      seizures and ictal signs during topiramate (TPM) treatment. METHODS: Twenty
      patients with refractory partial seizures undergoing presurgical evaluation were
      randomized into a low dosage (100 mg daily) and a parallel medium dosage (200 mg
      daily) group of TPM add-on medication. Study phases included a 3-day baseline
      video-EEG phase, a 10-day TPM titration phase without video-EEG and a 3-day TPM
      dose maintenance phase with video-EEG. During the baseline and the dose
      maintenance phase seizures were recorded using video-EEG monitoring and the
      following parameters were measured: duration (lasting seconds of each seizure and
      ictal sign), intensity (on a 0-3 scale), N/24 h (numbers of attacks per 24 h),
      D/24 h (duration per 24 h) of both seizures and defined ictal signs. RESULTS: A
      total of 399 seizures during the baseline phase and the dose maintenance phase
      were intensively analyzed. Intergroup comparison suggested that duration, N/24 h
      and D/24 h of all seizures decreased more in the medium dosage group computing
      the reduction from baseline to the dose maintenance phase (P<0.05). There were
      statistically more significant reductions in the duration, intensity and N/24 h
      of ictal signs like hypermotoric movements, fumbling and vocalization in the
      medium dosage group (P<0.05). CONCLUSION: Topiramate has an early dose-dependent
      effect on ictal seizures. SHORT COMMUNICATION: The present study intensively
      analyzed the duration, intensity, N/24 h and D/24 h of ictal seizure
      manifestations. The quantitative data suggested that topiramate had an early
      effect on ictal phenomena like ictal hypermotoric movements, fumbling and
      vocalization (P<0.05); effects were more prominent in the medium dosage group
      (200 mg daily) than the low dosage group (100 mg daily).

PMID- 11518629
TI  - FK506 facilitates chemical kindling induced by pentylenetetrazole in rats.
AB  - To clarify the possible role played by calcineurin in kindling development, we
      examined the effects of pretreatment with FK506, a selective calcineurin
      inhibitor, on pentylenetetrazole (PTZ) kindling in rats. FK506 facilitated the
      speed of kindling induced by repeated administration of 30-mg/kg PTZ, while FK506
      did not ameliorate acute seizure manifestations after a single injection of PTZ.
      Our results suggested that calcineurin might exert an inhibitory effect on PTZ
      kindling.

PMID- 11518630
TI  - Long-term observations of two siblings with Lafora disease treated with
      zonisamide.
AB  - We have reported long-term clinical follow-up for two siblings with Lafora
      disease, a brother and sister, one of whom autopsied. Both siblings had repeated
      attacks of severe myoclonus, tonic and tonic-clonic convulsions, and intractable
      status epilepticus. The addition of orally administered zonisamide brought about
      striking effective seizure control for about 12-14 years in both patients,
      relieving not only myoclonus and generalized tonic-clonic seizures but also
      intractable status epilepticus.

PMID- 11518631
TI  - Are personality traits associated with cognitive disturbance in psychosis?
AB  - OBJECTIVE: Personality and cognition are often considered as disparate
      constructs, both in normal individuals and in those with a psychosis. The goal of
      the present study was to analyze the relationship between dimensions of
      personality and cognitive performance in individuals with psychosis. METHODS:
      Sixty-one consecutively admitted patients with an acute psychotic episode were
      recruited for this study. Personality was assessed through a semistructured
      interview with a close relative using the Personality Assessment Schedule. A wide
      neuropsychological battery was applied, including attentional, executive, memory
      tasks and global cognition. Assessments took place when symptomatology was in
      remission. RESULTS: Higher scores on a passive-dependent dimension were
      significantly associated with poorer memory performance. Similarly, higher levels
      for a schizoid dimension were significantly associated with poorer executive
      performance. The results remained significant after partialling out the effect of
      gender, psychopathological dimensions and drug status. CONCLUSION: It is
      hypothesized that personality traits and cognitive performance are interrelated
      domains in psychosis.

PMID- 11518632
TI  - A comparison of verbal fluency tasks in schizophrenic patients and normal
      controls.
AB  - Previous studies have reported significant impairment on verbal fluency tasks
      (semantic and letter) among schizophrenic subjects. However, the possibility of
      specific categorical deficits has not been adequately investigated. Nor have the
      effects of task duration, the stability between testing sessions, and the
      relationship between intelligence and performance on fluency been thoroughly
      studied. We performed a series of 3 min fluency tasks (semantic/syntactic and
      letter) to determine whether duration specific or category-specific differences
      exist between schizophrenic subjects and normal controls. Each subject was tested
      at three different times as a means of estimating word pool and assessing the
      stability of fluency output. Subjects were asked to generate exemplars from each
      of four semantic/syntactic categories (animals, tools, common nouns and verbs)
      and three letters (G, E and T). Data from 13 schizophrenic subjects and 15 sex-,
      age- and pre-morbid-IQ-matched control subjects revealed that patients' overall
      performance on both the semantic and letter fluency tasks was impaired. While
      differential impairment on specific semantic categories was noted between groups,
      no differential effects relating to task duration or testing session were
      present. Further, by comparing the number of novel words produced in the three
      testing sessions, we found the groups to be equivalent, a finding we take to
      suggest that schizophrenic patients' lexicon is intact. Covarying current IQ
      eliminated the group difference robustly for letter fluency, while only
      marginally for semantic fluency. Our data revealed the presence of impairment in
      semantic and letter fluency tasks in schizophrenic patients consistent with
      previous reports, and also that patients were differentially impaired on semantic
      categories.

PMID- 11518633
TI  - Impaired conditional discrimination learning in schizophrenia.
AB  - Learning deficits have repeatedly been found in patients with schizophrenia.
      Eyelid conditional discrimination learning (ECDL) is a test of discriminative
      aversive conditioning and places minimal demands on motivation. An ECDL task was
      used to examine residual and paranoid type individuals with schizophrenia and age
      and gender-equivalent healthy controls. In the experiment two differently
      colored light stimuli were randomly presented. Only one of the stimuli (in
      reinforced trials) was followed by an aversive airpuff to the cornea, as opposed
      to unreinforced trials where the stimulus was not followed by an aversive
      airpuff. Conditioned responses develop to both trial types during the course of
      the experiment. These conditioned responses consist of reflectory eyelid closures
      already upon light presentation. The patients showed significantly impaired
      conditional discrimination learning abilities. There was no significant
      difference between the results in the two schizophrenia subtypes. Patients failed
      to increase response frequencies on reinforced trials during the course of the
      experiment, while controls showed appropriate conditional discrimination ability.
      Thus the results show an impairment of adequate behavior modification in an
      aversive conditioning task in individuals with schizophrenia. It is concluded
      that ECDL might be a trait marker for schizophrenia.

PMID- 11518634
TI  - Temporal order and spatial memory in schizophrenia: a parametric study.
AB  - Spatial working memory has been shown to be impaired in schizophrenia. In
      contrast, memory for temporal order has been poorly studied in patients with
      schizophrenia. The aim of this study was to compare and to further characterize
      spatial working memory and sequence reproduction deficits in patients with
      schizophrenia under stable medication by manipulating cues (pattern versus
      sequence), delay, set-size and response type in various recall and recognition
      tasks. This allowed us to dissociate processes as encoding, retention and
      retrieval and to compare the performance of patients with schizophrenia to the
      performance of patients with prefrontal lesions, who have been previously tested
      in the same tasks. Our results show that increase of the set-size and of the
      delay decreased performance of both groups, and that these factors had larger
      detrimental effects in patients with schizophrenia than in controls. Furthermore,
      comparison between tasks revealed retention and retrieval deficits in
      schizophrenia. Finally, patients with schizophrenia showed impairments not only
      in recall but also in sequence recognition tasks with delay. This is in contrast
      to patients with prefrontal lesions, who have previously been shown to have
      intact recognition of sequences after a delay. These results suggest that the
      working memory deficit in schizophrenia cannot be restricted to a prefrontal
      dysfunction.

PMID- 11518635
TI  - Clinical features of latent inhibition in schizophrenia.
AB  - Paradigms of Latent Inhibition (LI) are inter-species and derived from learning
      theories. They are considered as tools which allow the attentional processes to
      be studied. The absence of LI is interpreted as difficulty in discriminating
      relevant and irrelevant stimuli. Abolition of LI has been shown in acute
      schizophrenics. The objectives of our study were partly to validate an LI
      paradigm, based on a contingency detection between two stimuli, in healthy
      subjects, and partly to analyse LI in schizophrenics. The study included 105
      subjects (65 patients and 40 controls). Patients fulfilled the DSM IV diagnosis
      of schizophrenia. 35 in the acute phase and 30 in the chronic phase. We observed
      a loss of LI for acute schizophrenics, and an enhancement of LI for chronic
      schizophrenics. The variations in LI are interpreted from the perspective of a
      disturbance in the attentional processes. The LI status in acute schizophrenics
      appears to correlate with the clinical criteria with a prognostic value (low
      intensity of the negative dimension, late age at the first hospitalization).
      Moreover, the enhancement of LI correlates with the negative dimension of
      schizophrenic disease. This correlation is found in acute and chronic
      schizophrenics. It suggests that the variations of LI may be an indicator of
      adaptive strategies to a cognitive dysfunction specific to schizophrenia.

PMID- 11518636
TI  - Auditory distraction and thought disorder in chronic schizophrenic inpatients.
      Evidence for separate contributions by incapacity and poor allocation and a
      subsyndrome related to the allocation deficit.
AB  - This study investigated auditory attentional processes associated with
      schizophrenic thought disorder. Thirty-five chronically schizophrenic, state
      hospital inpatients were assessed for thought disorder using the Thought,
      Language, and Communication Disorders Scale (TLC) and tested in an attentional
      task. Two measures of attention were derived from the Digit Span Distraction Test
      (DSDT) (Oltmannns, T.F., Neale, J.M., 1975. Schizophrenic performance when
      distractors are present: attentional deficit or differential task difficulty. J.
      Abnorm. Psychol. 84, 205-209), a digit recall task in which distractor digits
      were interspersed with target digits. The two measures were Distractibility --
      the overall inaccuracy of recall -- which measured attentional incapacity, and
      Distractible Intrusion -- the number of irrelevant digits recalled -- which was
      developed in this study to separately measure the inability to allocate
      attentional resources. These two measures predicted thought disorder strongly and
      independently. Distractibility did not significantly correlate with any TLC
      subscale. In contrast, Distractible Intrusions correlated with the TLC subscales
      Distractible Speech, Incoherence, Loss of Goal, and Word Approximations. The
      present findings suggest that these subtypes may comprise a distinct subsyndrome
      of thought disorder, characterized by a dysfunctionally low threshold for
      selecting appropriate speech information, and that an attentional allocation
      deficit is related to this language dysfunction.

PMID- 11518637
TI  - Quality of life in schizophrenia: contributions of anxiety and depression.
AB  - A number of studies have demonstrated a strong relationship between quality of
      life in schizophrenia and general psychopathology measures, and moreover, that
      the positive, negative, and disorganized symptoms are less related to quality of
      life. The current investigation examined the relationship between quality of life
      and symptomatology in 63 stabilized outpatients diagnosed with schizophrenia or
      schizoaffective disorder. Consistent with other findings, more severe depression,
      as rated on the Brief Psychiatric Rating Scale (BPRS) was associated with lower
      general life satisfaction and lower satisfaction with daily living, finances,
      health, and social life. In addition, higher anxiety ratings on the BPRS were
      associated with less satisfaction with global quality of life, daily activities,
      family, health and social relationship, even when controlling for positive
      symptoms, negative symptoms, or depression. No other symptoms of schizophrenia
      were as strongly associated with subjective quality of life. Anxiety was also
      significantly correlated with a number of positive and negative symptoms while
      depression was substantially less related. These findings, suggest that more
      precise analyses of general psychopathology, and anxiety in particular, may be
      necessary to further clarify the factors involved in quality of life in
      schizophrenia. In addition, these findings suggest future directions for theories
      of affect and treatment in schizophrenia.

PMID- 11518642
TI  - Comparison of animal models for the evaluation of radiolabeled androgens.
AB  - Biodistribution of two 18F-labeled androgens and an 124I/125I-labeled androgen
      were studied in five androgen receptor (prostate) animal models with or lacking
      sex hormone binding globulin (SHBG). As models for androgen-receptor positive
      ovarian cancer, xenografts of three human ovarian cancer cell lines were tested
      in SCID mice. SHBG in the prostate model systems significantly affects the
      metabolism, clearance, and distribution of the radiolabeled androgens in several
      tissues, but ovarian cancer animal models were disappointing.

PMID- 11518643
TI  - Clinical correlative evaluation of an iterative method for reconstruction of
      brain SPECT images.
AB  - BACKGROUND: Brain SPECT and PET investigations have showed discrepancies in
      Alzheimer's disease (AD) when considering data deriving from deeply located
      structures, such as the mesial temporal lobe. These discrepancies could be due to
      a variety of factors, including substantial differences in gamma-cameras and
      underlying technology. Mesial temporal structures are deeply located within the
      brain and the commonly used Filtered Back-Projection (FBP) technique does not
      fully take into account either the physical parameters of gamma-cameras or
      geometry of collimators. In order to overcome these limitations, alternative
      reconstruction methods have been proposed, such as the iterative method of the
      Conjugate Gradients with modified matrix (CG). However, the clinical applications
      of these methods have so far been only anecdotal. The present study was planned
      to compare perfusional SPECT data as derived from the conventional FBP method and
      from the iterative CG method, which takes into account the geometrical and
      physical characteristics of the gamma-camera, by a correlative approach with
      neuropsychology. METHODS: Correlations were compared between perfusion of the
      hippocampal region, as achieved by both the FBP and the CG reconstruction
      methods, and a short-memory test (Selective Reminding Test, SRT), specifically
      addressing one of its function. A brain-dedicated camera (CERASPECT) was used for
      SPECT studies with 99mTc-hexamethylpropylene-amine-oxime in 23 consecutive
      patients (mean age: 74.2 +/- 6.5) with mild (Mini-Mental Status Examination score
      > or =15, mean 20.3 +/- 3), probable AD. Counts from a hippocampal region in each
      hemisphere were referred to the average thalamic counts. RESULTS: Hippocampal
      perfusion significantly correlated with the MMSE score with similar statistical
      significance (p < 0.01) between the two reconstruction methods. Correlation
      between hippocampal perfusion and the SRT score was better with the CG method (r
      = 0.50 for both hemispheres, p < 0.01) than with the FBP method (r = 0.37 and
      0.43, respectively for the right and left hemisphere, p < 0.05 and p < 0.02). The
      bootstrap procedure showed that such correlation indexes were statistically
      different both in the right (p < 0.01) and in the left (p < 0.05) hemisphere.
      CONCLUSION: These results are interpreted as a better performance of the CG
      reconstruction method in correctly detecting counts from hippocampal ROI. By
      using the same gamma-camera or collimator, alternative methods for brain SPECT
      reconstruction may improve quality of data and then help SPECT diagnostic
      accuracy.

PMID- 11518644
TI  - [14C]Serotonin uptake and [O-methyl-11C]venlafaxine kinetics in porcine brain.
AB  - As part of our program of developing PET tracers for neuroimaging of psychotropic
      compounds, venlafaxine, an antidepressant drug, was evaluated. First, we measured
      in vitro rates of serotonin uptake in synaptosomes prepared from selected regions
      of porcine brain. Then, we determined the pharmacokinetics of venlafaxine, [O
      methyl-11C]-labeled for PET. Synaptosomal studies showed that the active uptake
      of [14C]5-HT differed markedly between brain regions, with highest rates in
      hypothalamus, raphe region, and thalamus, and lowest rates in cortex and
      cerebellum. PET studies showed that the unidirectional rate of uptake of [O
      methyl-11C]venlafaxine from blood to brain was highest in the hypothalamus, raphe
      region, thalamus and basal ganglia and lowest in the cortex and cerebellum. Under
      normal physiological conditions, the capillary permeability-surface area (PS)
      product for [O-methyl-11C]venlafaxine could not be estimated, because of complete
      flow-limitation of the cerebral uptake. Nevertheless, a correlation occurred
      between the apparent partition volume of the radiotracer and the rate of active
      uptake of 5-HT in selected regions of the porcine brain. During hypercapnia,
      limitations of blood-brain transfer were observed, giving PS-products for water
      that were only ca. 50% higher than those of venlafaxine. Thus, under normal
      physiological conditions, the rate of uptake of venlafaxine from blood into brain
      is completely flow-limited.

PMID- 11518645
TI  - In vivo evaluation of 4-[123I]iodo-N-[2[4-(6-trifluoromethyl-2-pyridinyl)-1
      piperazinyl]ethyl]benzamide, a potential SPECT radioligand for the 5-HT1A
      receptor.
AB  - 4-[123I]Iodo-N-[2-[4-(6-trifluoromethyl-2-pyridinyl)-1
      piperazinyl]ethyl]benzamide (1.123I), a potential SPECT 5-HT(1A) radioligand, was
      evaluated in vivo in rats. Biodistribution studies were performed leading to a %
      ID in the brain of 0.22 at 5 min p.i. No significant differences in % ID/g tissue
      of the different isolated brain regions (hippocampus, hypothalamus, striatum,
      cortex and cerebellum) could be demonstrated. Blocking experiments with 8-OH
      DPAT, WAY100635 and ketanserin could not show any significant change in tracer
      uptake in the isolated brain regions. These data suggest that uptake in the brain
      does not represent binding of 1.123I to the 5-HT(1A) receptor.

PMID- 11518646
TI  - Synthesis and in vivo studies of the stereoisomers of N-[11C]methyl
      homoepibatidine.
AB  - The carbon-11 labeled enantiomers of nicotinic acetylcholine receptor (nAChR)
      ligand N-[11C]methyl-homoepibatidine have been synthesized to study the neuronal
      nicotinic acetylcholine receptors (nAChRs). In vivo evaluations were performed in
      mice and pig using positron emission tomography (PET). The radioligands displayed
      a strong enantioselectivity. The (-)-enantiomer showed high uptake in the brain
      while the (+)-enantiomer was rapidly washed out. In metabolite studies in mice
      >65% unchanged ligand was found in the blood after 60 minutes. No metabolites
      were found in the brain. After intravenous application of N-[11C]methyl-(-)
      homoepibatidine in the pig specific accumulation in the thalamus was seen.
      Blocking experiments with cytisine showed specific binding consistent with
      labeling of the alpha4beta2-nAChR-subtype in the brain. Quantitative kinetic
      modeling of radiotracers in the pig brain was performed using the arterial input
      function. The brain uptake of the (-)-isomer was best fitted by a three
      compartment model. High distribution volumes were found in the thalamus (DV(TOT)
      = 66.617, DV(S) = 59.910) versus a low uptake in the cerebellum (DV(TOT) =
      8.605m, DV(S) = 1.898). The binding characteristics suggest N-[11C]methyl-(-)
      homoepibatidine to be suited for PET imaging studies, but high toxicity prevents
      routine use in humans.

PMID- 11518647
TI  - Development of a Tc-99m labeled sigma-2 receptor-specific ligand as a potential
      breast tumor imaging agent.
AB  - A novel in vivo imaging agent, 99mTc labeled [(N-[2-((3'-N'-propyl-[3,3,1]aza
      bicyclononan-3alpha-yl)(2"-methoxy-5-methyl-phenylcarbamate)(2
      mercaptoethyl)amino)acetyl]-2-aminoethanethiolato] technetium(V) oxide),
      [99mTc]2, displaying specific binding towards sigma-2 receptors was prepared and
      characterized. In vitro binding assays showed that the rhenium surrogate of
      [99mTc]2, Re-2, displayed excellent binding affinity and selectivity towards
      sigma-2 receptors (K(i) = 2,723 and 22 nM for sigma-1 and sigma-2 receptor,
      respectively). Preparation of [99mTc]2 was achieved by heating the S-protected
      starting material, 1, in the presence of acid, reducing agent (stannous
      glucoheptonate) and sodium [99mTc]pertechnetate. The lipophilic racemic mixture
      was successfully prepared in 10 to 50% yield and the radiochemical purity was
      >98%. Separation of the isomers, peak A and peak B, was successfully achieved by
      using a chiralpak AD column eluted with an isocratic solvent (n
      hexane/isopropanol; 3:1; v/v). The peak A and peak B appear to co-elute with the
      isomers of the surrogate, Re-2, under the same HPLC condition. Biodistribution
      studies in tumor bearing mice (mouse mammary adenocarcinoma, cell line 66, which
      is known to over-express sigma-2 receptors) showed that the racemic [99mTc]2
      localized in the tumor. Uptake in the tumor was 2.11, 1.30 and 1.11 %dose/gram at
      1, 4 and 8 hr post iv injection, respectively, suggesting good uptake and
      retention in the tumor cells. The tumor uptake was significantly, but
      incompletely, blocked (about 25-30% blockage) by co-injection of "cold"
      (+)pentazocine or haloperidol (1 mg/Kg). A majority of the radioactivity
      localized in the tumor tissue was extractable (>60%), and the HPLC analysis
      showed that it is the original compound, racemic [99mTc]2 (>98% pure). The
      distribution of the purified peak A and peak B was determined in the same tumor
      bearing mice at 4 hr post iv injection. The tumor uptake was similar for both
      isomers, but the blood and peripheral tissue content for the isomer in peak B was
      higher than that for the isomer in peak A. It is evident that the isomer in peak
      A displayed significantly better tumor/blood and tumor/muscle ratios. The higher
      rate of in vivo metabolism was also confirmed by the higher thyroid uptake values
      for the isomer in peak B as compared to peak A. In summary, a 99mTc-labeled sigma
      receptor imaging agent, [99mTc]2, has demonstrated the feasibility of using a
      99mTc-labeled agent for imaging sigma receptor expression in tumor cells. This is
      the first time a subtype-selective 99mTc-labeled agent for imaging sigma receptor
      sites is reported.

PMID- 11518648
TI  - New radiolabeled CCK-8 analogues [Tc-99m-GH-CCK-8 and Tc-99m-DTPA-CCK-8]:
      preparation and biodistribution studies in rats and rabbits.
AB  - The aim of this study is to label CCK-8 with Tc-99m and to investigate its
      radiopharmaceutical potential. CCK-8 was labeled with Tc-99m using GH and DTPA as
      bifunctional chelating agents. Labeling efficiency was higher than 99%. Complex
      was stable more than 5 hours at room temperature. 37 MBq Tc-99m-GH-CCK-8 or Tc
      99m-DTPA-CCK-8 was administered intravenously to rabbits for biodistribution
      experiments. Dynamic and static images were obtained from anterior projection
      using a Camstar XC/T gamma camera. For quantitative evaluation, regions of
      interest were drawn on organs and time-activity curves were generated. The
      highest accumulation occurred in brain within 10 and 30 minutes after injection.
      Renal and hepatobiliary excretion were observed. Brain distribution studies in
      rats showed the highest activity was in hypothalamus. Results demonstrated that
      Tc-99m-GH-CCK-8 and Tc-99m-DTPA-CCK-8 analogs may be a useful new class of
      receptor-binding peptides for diagnosis and therapy of brain diseases related
      with CCK-B receptor-expressing tumors.

PMID- 11518649
TI  - Biological evaluation of 2-fluoro-2-[123I]iodo-mannose (FIM): biological
      evaluation of FIM.
AB  - This paper describes the biodistribution of a radio-iodinated analog of
      fluorodeoxyglucose (FDG). 123I-2-fluoro-2-iodo-mannose (FIM) was investigated as
      a potential single photon emission tomography (SPECT) imaging agent. We also
      compare the results with the observed distribution of the classical PET agent 18F
      FDG and newly developed 18F-difluorodeoxyglucose (DFDG). Following
      radioiodination, the final product was stable in-vitro for 24 hrs. Mice showed a
      rapid blood clearance and deiodination of the 123I-FIM reflected by high stomach
      and thyroid uptake. Comparison with 18F-FDG and 18F-DFDG revealed a large
      discrepancy between the 18F labeled sugars and the 123I-FIM biological
      distribution. The iodinated product was not found to be a metabolic marker for in
      vivo studies.

PMID- 11518650
TI  - Synthesis and properties of 18F-labeled potential myocardial blood flow tracers.
AB  - PET centers without particle accelerators make clinical PET widely available at
      reduced cost. For myocardial perfusion tracers, these satellite PET centers are
      limited to generator- produced 82Rb(+) and 62Cu[PTSM]. Their limitations motivate
      a search for transportable alternatives. In search of new tracers we have
      synthesized several 18F-labeled amines and quaternary ammonium salts. Among them,
      4-[18F]fluorotri-N-methylanilinium ([18F]FTMA) has flow-tracing properties. The
      compound is functional, but has properties that justify a continued search.

PMID- 11518651
TI  - In vitro and in vivo characterization of 67Ga(3+) complexes with cis,cis-1,3,5
      triamino-cyclohexane-N,N',N"-triacetic acid derivatives.
AB  - The aim of this study was to investigate the in vitro and in vivo performance of
      a 67Ga complex with cis,cis-1,3,5-triaminocyclohexane-N,N',N"-triacetic acid
      (tachta) as a potential ligand for use as a Ga(III) radiopharmaceutical for PET
      imaging. The radiolabeling procedure, electrophoretic properties, lipophilicity,
      acid stability, human serum stability and biodistribution in mice of 67Ga(tachta)
      were investigated. The 67Ga(tachta) complex forms at 10(-3) M tachta
      concentration at 40 degrees C in 100% yield; it is neutral, non-lipophilic, 90%
      stable at pH = 4 and 5 and 100% stable at pH = 6, for at least 8 d. Serum
      stability experiments demonstrated that at 5 hr 67Ga(tachta) exists in serum as a
      free complex. At 24 hr, 30% of 67Ga(tachta) is reversibly bound to transferrin
      albumin fraction of serum, and that this percentage remains unchanged for a
      period of 4 d. Biodistribution in mice showed that 67Ga(tachta) rapidly clears
      via the kidneys from the body with less than 10% of injected activity left in the
      body at 3 hours and only 6% remaining after 24 hr. The complex also cleared
      rapidly from all of the major organs, with bone showing some slightly increased
      (1.15% ID/g) 24 hr accumulation, in comparison with the 3 hr time point. Based
      upon these data, 67Ga(tachta) may be considered as a candidate for developing new
      Ga(III) radiopharmaceuticals for PET.

PMID- 11518652
TI  - A novel and simplified route to the synthesis of N3S chelators for 99mTc
      labeling.
AB  - As one example of a N(3)S chelator, MAG(3) has been used successfully for
      labeling peptides, proteins, DNAs and other carriers with 99mTc. We now report on
      a simplified route to the synthesis of N(3)S chelators. As a test of the
      approach, we have synthesized the succinimidyl ester of S-acetylmercaptoacetyl
      (L)-glutamyl(gamma-O-t-Bu)glycylglycolic acid (MAGluG(2)) (thus MAG(3) with a t
      butyl protected carboxyl group on the backbone via an ethylene linker) and the
      succinimidyl ester of S-acetylmercaptoacetyl-phenylalanyl-glycylglycolic acid
      (MAPheG(2)) (thus MAG(3) with a benzyl group on the backbone). The first chelator
      was selected to provide a free carboxyl group in the backbone after conjugation
      to peptides and after t-butyl deprotection whereas the second chelator was
      selected for its expected lipophilicity. The Fmoc protected NHS ester of the
      corresponding glutamic acid and phenylalanine were purchased and each was reacted
      with diglycine followed by Fmoc deprotection to provide the tripeptide. This was
      reacted with SATA and the NHS ester added via DCC to provide the final NHS ester
      of MAGluG(2) or MAPheG(2). After purification, both NHS-derivatives were
      conjugated to HNE2 (a 7 kDa neutrophil elastase inhibitor) as a test polypeptide.
      In the MAGluG(2) case, t-butyl deprotection was performed after peptide
      conjugation. Both of the conjugated HNE2 peptides were radiolabeled with 99mTc by
      transchelation from tartrate as is routine for the labeling of MAG(3)-conjugated
      carriers. Labeling efficiencies and stability of the chelated 99mTc towards
      cysteine transchelation were identical for HNE2 labeled via MAGluG(2), MAPheG(2)
      and MAG(3). A 3 hr biodistribution of 99mTc radiolabels in normal mice showed
      significant differences between the three labeled HNE2, especially in major
      organs (liver and kidneys). We conclude that this synthesis route provides a
      simplified path to the synthesis of N(3)S chelators which in principle may be
      used to incorporate any natural or unnatural amino acid.

PMID- 11518653
TI  - 186Re-1,4,8,11-tetraaza cyclotetradecyl-1,4,8,11-tetramethylene phosphonic acid:
      a novel agent for possible use in metastatic bone-pain palliation.
AB  - In connection with our work on the development of 186Re-tetra-phosphonates with
      optimum properties for use in bone pain palliation, a novel cyclic
      tetraphosphonate derivative, has been synthesized, complexed with 186Re and
      evaluated with promising results. The ligand, which consists of a cyclic array of
      tetra-aminomethylphosphonate groups, was synthesized using orthophosphorus acid,
      1,4,8,11-tetraazacyclotetradecane and formaldehyde. The labeling conditions with
      186Re have been standardized under varying reaction conditions to give maximum
      yield. In a reaction volume of 1 mL, maximum complexation yield of 98% was
      observed at pH 2 using 0.1 mg Re (37-370 MBq) for a ligand concentration at 9 x
      10(-2) M/L, under heating at 100 degrees C for 30 min with 2 mg of stannous
      chloride. The complex was found to be stable for 6 days with RC purity remaining
      approximately 97%. The complex was characterized by paper chromatography in
      saline and acetone, wherein the R(f) exhibited were 0.9 and 0, respectively.
      Biodistribution studies of the complex were performed in male Wistar rats.
      Activity in femur which was observed to be 1.8%/g (equivalent to about 23% of the
      injected activity in skeleton) at 3 h post injection remained almost constant up
      to 48 h. Minimum activity was observed in blood and other soft tissues. The
      complex showed major renal clearance. Scintigraphic images in rabbits after
      injecting 70-100 MBq of 186Re-CTMP and using a dual head gamma camera were
      observed to be superior to 186Re-HEDP, prepared by a procedure standardized by
      us. Insignificant activity was observed in other vital organs. The results
      suggest the suitability of the complex for further evaluation in higher animals
      for bone pain palliation.

PMID- 11518654
TI  - Preparation of 153Sm-chitosan complex for radiation synovectomy.
AB  - A samarium 153-chitosan complex was prepared by simply mixing acidic solutions of
      chitosan and (153)SmCl(3). When a solution of this complex was injected into the
      knee joints of rabbits, minimal extra-articular leakage was observed. This can be
      attributed to the rapid change in the pH of the complex solution from acidic to
      neutral, resulting in the formation of gel followed by the subsequent retention
      in the administered site. Thus, the complex solution represents a promising
      candidate for radiation synovectomy.

PMID- 11518655
TI  - Histologic study of effects of radiation synovectomy with Rhenium-188
      microsphere.
AB  - Rhenium-188 microsphere is a relatively new radiation synovectomy agent developed
      for the treatment of rheumatoid arthritis. It has been shown that the levels of
      unwanted extra-articular radiation are negligible with this agent. A histologic
      study was conducted to assess the effect of radiation synovectomy on synovium and
      articular cartilage after intra-articular injection of various doses of Re-188
      microspheres into the knee joints of rabbits. Intra-articular injection of Re-188
      microspheres into rabbit knee joints resulted in mild reactive inflammation and
      thrombotic occlusion of vessels which subsided rapidly. Sclerosis of subsynovium
      could be seen 12 weeks after injection. No evidence of damage to articular
      cartilage was noted. There was no significant difference in the articular pattern
      after injection of 0.3 or 0.6 mCi Re-188 microspheres. This study suggests that a
      treatment dose of Re-188 microspheres causes transient inflammation of synovium
      without any detectable damage to the articular cartilage of knee joint.

PMID- 11518658
TI  - Purification and stabilization of 99mTc-d,l-HMPAO: role of organic extractants.
AB  - 99mTc-d,l-HMPAO, an important SPECT agent for imaging cerebral perfusion, suffers
      from the disadvantage of an inherent instability and its shelf life has been
      reported to be 30 min. The latter is a harsh constraint and not compatible with
      Centralized Radiopharmacy procedures. During the attempts to improve upon the
      stability of 99mTc-d,l-HMPAO, preservation of product as an organic extract into
      suitable solvents like diethylether, ethylacetate, methylethylketone, chloroform
      was tried out. Chloroform extraction (yield: >90%) resulted in a product having
      stability not less than 5 hours. Gentle drying of the chloroform extract and
      reconstitution in normal saline resulted in quantitative recovery of 99mTc-d,l
      HMPAO with acceptable radiochemical purity (>90%). This finding is thus of much
      significance, especially in the context of centralized large hospital
      radiopharmacy setting, by rendering convenience and flexibility in scheduling
      patients.

PMID- 11518657
TI  - Study of tea polyphenol as a reversal agent for carcinoma cell lines' multidrug
      resistance (study of TP as a MDR reversal agent).
AB  - The aim of this study was to examine MDR1 expression product P-glycoprotein (Pgp)
      and study the effect and mechanism of tea polyphenol (TP) in reversion of
      multidrug resistance (MDR) in carcinoma cell lines. Immunocytochemical method was
      used for qualitative detection of Pgp. A comparative study of cytotoxicity and
      multidrug resistance reversion effect was made by MTT assay for tea polyphenol
      and quinidine in MCF-7 and MCF-7/Adr cell lines. The multidrug resistance
      reversion effect and mechanism were studied by measuring the uptake of 99mTc
      tetrofosmin in the carcinoma cell lines. (1) The Pgp overexpression in MCF-7/Adr
      cells was found to be strong positive, while the Pgp expression of MCF-7 was
      negative. (2) Although both tea polyphenol and quinidine could not remarkably
      change the toxicity of adriamycin to MCF-7, they could improve the sensitivity of
      MCF-7/Adr to adriamycin. The reversion index of tea polyphenol and quinidine was
      3 and 10 respectively. (3) The cellular uptake of 99mTc-tetrofosmin was
      remarkably lower in MCF-7/Adr than in MCF-7. The uptake of 99mTc-tetrofosmin in
      MCF-7/Adr exhibited a 4, 13, 16 fold increase in the presence of 200, 400 and 500
      microg/ml of tea polyphenol respectively. The uptake of 99mTc-tetrofosmin in MCF
      7/Adr exhibited only a 4-fold increase in the presence of 200 microM of
      quinidine. Immunocytochemistry can detect P-glycoprotein expression level
      qualitatively. Tea polyphenol is not only an anti-tumor agent, but also a
      multidrug resistant modulator similar to quinidine. The multidrug resistance
      reversion mechanism of tea polyphenol seems to be its inhibition of the activity
      of P-glycoprotein. Tea polyphenol has the advantage of very low toxicity in tumor
      treatment.

PMID- 11518659
TI  - Parameters ruling optimization of radiolabelling of polyamino polycarboxylated
      functionalized peptide derivatives: a case study report.
AB  - Parameters studies revealed that successful labeling of DTPA-Neurotensin(8-13)
      analogues depend on several physico-chemical parameters. The pH of the reaction
      mixture seemed to be the most critical parameter for obtaining high labeling
      yields; quantitative radiolabelling was only guaranteed at a pH between 4.2 and
      5.5. At a pH of 4.5, metal ion contaminants originating from peptide synthesis
      and purification procedures were shown not to effect radiolabelling.
      Nevertheless, proper reducing agents were included in a proposed Kit labeling
      procedure in order to avoid potential competition from trivalent metal ion
      contamination, and thus guarantee successful 111In-complexation. The complexing
      capacity of DTPA for radioactive In(3+) strongly depends upon the pH. As a
      consequence, labeling yields must be expressed as [[K(ass) x alpha(4) x [DTPA
      NT](0)/(1+ K(ass) x alpha(4) x [DTPA-NT](0))], to where K(ass) is the association
      constant and alpha(4) is a pH dependent correction factor of the association
      constant.

PMID- 11518656
TI  - A simple synthesis of [11C]carfentanil using an extraction disk instead of HPLC.
AB  - [11C]Carfentanil was prepared without the need for purification by HPLC. The
      tetrabutylammonium salt of the precursor carboxylate was reacted with [11C]methyl
      triflate in DMSO. The resulting [11C]carfentanil was trapped on an Empore
      extraction disk and washed to remove precursor and most radioactive contaminants.
      The product was eluted by a small volume of ethanol, mixed with water and passed
      through a small column containing fibrous anion exchanger to remove remaining
      radioactive contaminants.

PMID- 11518660
TI  - Intelligent medical systems - preface.

PMID- 11518661
TI  - Knowledge management in healthcare: towards 'knowledge-driven' decision-support
      services.
AB  - In this paper, we highlight the involvement of Knowledge Management in a
      healthcare enterprise. We argue that the 'knowledge quotient' of a healthcare
      enterprise can be enhanced by procuring diverse facets of knowledge from the
      seemingly placid healthcare data repositories, and subsequently operationalising
      the procured knowledge to derive a suite of Strategic Healthcare Decision-Support
      Services that can impact strategic decision-making, planning and management of
      the healthcare enterprise. In this paper, we firstly present a reference
      Knowledge Management environment-a Healthcare Enterprise Memory-with the
      functionality to acquire, share and operationalise the various modalities of
      healthcare knowledge. Next, we present the functional and architectural
      specification of a Strategic Healthcare Decision-Support Services Info-structure,
      which effectuates a synergy between knowledge procurement (vis-a-vis Data Mining)
      and knowledge operationalisation (vis-a-vis Knowledge Management) techniques to
      generate a suite of strategic knowledge-driven decision-support services. In
      conclusion, we argue that the proposed Healthcare Enterprise Memory is an attempt
      to rethink the possible sources of leverage to improve healthcare delivery,
      hereby providing a valuable strategic planning and management resource to
      healthcare policy makers.

PMID- 11518662
TI  - Hybrid expert system for decision supporting in the medical area: complexity and
      cognitive computing.
AB  - This paper proposes a hybrid expert system (HES) to minimise some complexity
      problems pervasive to the artificial intelligence such as: the knowledge
      elicitation process, known as the bottleneck of expert systems; the model choice
      for knowledge representation to code human reasoning; the number of neurons in
      the hidden layer and the topology used in the connectionist approach; the
      difficulty to obtain the explanation on how the network arrived to a conclusion.
      Two algorithms applied to developing of HES are also suggested. One of them is
      used to train the fuzzy neural network and the other to obtain explanations on
      how the fuzzy neural network attained a conclusion. To overcome these
      difficulties the cognitive computing was integrated to the developed system. A
      case study is presented (e.g. epileptic crisis) with the problem definition and
      simulations. Results are also discussed.

PMID- 11518663
TI  - Generation of an intelligent medical system, using a real database, to diagnose
      bacterial infection in hospitalized patients.
AB  - The initial diagnosis of bacterial infections in the absence of laboratory
      microbiological data requires physicians to use clinical algorithms based on
      symptoms, patient history and infection site. Optimization of such algorithms
      would be achieved by including as many variables associated with bacterial
      infection as possible. Demographic data are easily available and frequently used
      to sub-group human populations. A prospective investigation was, therefore,
      undertaken to examine the influence of demographic variables on bacterial
      infection rates, using data obtained from 173 patients presenting to Albert
      Einstein Medical Center. Data was randomly selected from 149 of these patients
      and used to generate fuzzy rules to model an intelligent medical system. To test
      the accuracy of this system at determining bacterial infection, based solely on
      demographic data, the program was given the remaining 24 patients' information.
      All 18 patients with either streptococcal, staphylococcal or Escherichia coli
      infections were correctly diagnosed. Non-E.coli GNR were misdiagnosed as E. coli
      infections in two patients resulting in an overall prediction rate for the 24
      patients of 91.66%. This study suggests that the direct correlation of
      demographic variables with a predisposition to bacterial infection allow the
      design of an intelligent medical system, which shows great future potential as a
      diagnostic tool for all physicians.

PMID- 11518665
TI  - Diagnostics and a qualitative model.
AB  - First generation expert systems were using shallow knowledge based on heuristic
      information to solve a diagnostic problem. This approach has many disadvantages,
      which can be avoided by using deep knowledge. Diagnostic reasoning based on deep
      knowledge is called model-based diagnostics. Recently, the use of qualitative
      modeling in relation to deep knowledge in expert systems has become increasingly
      important. The main purpose of our contribution is to present the model-based
      diagnostic approach at a formal level. The originality of the presented
      formalization is the concept of the diagnostic space, the characterization of the
      minimal diagnoses, and the measurement. The formalization serves as the
      theoretical background to prove our view to the design of qualitative system
      models and to establish the diagnostic architecture called DISY. The qualitative
      system model in our diagnostic approach needs not to be specially adopted for use
      in the diagnostic domain. The only requirement is that it must simulate the
      system behavior expressed by normal or abnormal functioning of its components.
      Proposed DISY architecture is not complex and simply takes into an account the
      previous diagnostic result to obtain a new one from the additional observation
      measurement (medical tests or examinations) of the system.

PMID- 11518664
TI  - Feature mining and predictive model construction from severe trauma patient's
      data.
AB  - In management of severe trauma patients, trauma surgeons need to decide which
      patients are eligible for damage control. Such decision may be supported by
      utilizing models that predict the patient's outcome. The study described in this
      paper investigates the possibility to construct patient outcome prediction models
      from retrospective patient's data at the end of initial damage control surgery by
      using feature mining and machine learning techniques. As the data used comprises
      rather excessive number of features, special attention was paid to the problem of
      selecting only the most relevant features. We show that a small subset of
      features may carry enough information to construct reasonably accurate prognostic
      models. Furthermore, the techniques used in our study identified two factors,
      namely the pH value when admitted to ICU and the worst partial active
      thromboplastin time, to be of highest importance for prediction. This finding is
      pathophysiologically reasonable and represents two of three major problems with
      severe trauma patients, metabolic acidosis, hypothermia, and coagulopathy.

PMID- 11518666
TI  - Medical applications of enhanced rule-based expert systems.
AB  - The paper describes several types of efficiency enhancements of 'classical' rule
      based diagnostic expert systems. The blackboard control structure enables to
      explore more knowledge bases of the same syntax in parallel, the taxonomy
      structures make fast zooming of attention possible and provide additional
      inference mechanism based on inheritance principles. The applicability of the
      enhancing techniques is documented by four case studies exploring the extended
      FEL-EXPERT shell in different tasks of medical decision-making. The authors
      consider the enhancing techniques as useful steps on the way from 'classical'
      diagnostic expert systems towards more complex multi-agent decision tools.

PMID- 11518667
TI  - Processing and representation of meta-data for sleep apnea diagnosis with an
      artificial intelligence approach.
AB  - In this article, we revise and try to resolve some of the problems inherent in
      questionnaire screening of sleep apnea cases and apnea diagnosis based on
      attributes which are relevant and reliable. We present a way of learning
      information about the relevance of the data, comparing this with the definition
      of the information by the medical expert. We generate a predictive data model
      using a data aggregation operator which takes relevance and reliability
      information about the data into account to produce a diagnosis for each case. We
      also introduce a grade of membership for each question response which allows the
      patient to indicate a level of confidence or doubt in their own judgement. The
      method is tested with data collected from patients in a Sleep Clinic using
      questionnaires specially designed for the study. Other artificial intelligence
      predictive modeling algorithms are also tested on the same data and their
      predictive accuracy compared to that of the aggregation operator.

PMID- 11518668
TI  - Detection of hemodynamic changes in clinical monitoring by time-delay neural
      networks.
AB  - Small changes that occur in a patient's physiology over long periods of time are
      difficult to detect, yet they can lead to catastrophic outcomes. Detecting such
      changes is even more difficult in intensive care unit (ICU) environments where
      clinicians are bombarded by a barrage of complex monitoring signals from various
      devices. Early detection accompanied by appropriate intervention can lead to
      improvement in patient care. Neural networks can be used as the basis for an
      intelligent early warning system. We developed time-delay neural networks (TDNN)
      for classifying and detecting hemodynamic changes. A matrix of physiological
      parameters were extracted from raw signals collected during cardiovascular
      experiments in mongrel dogs. These matrices represented several episodes of
      stable, decreasing, and increasing cardiac filling in normal, exerted, and heart
      failure conditions. The TDNN were trained with these matrices and subsequently
      tested to predict unseen cases. The TDNN perform remarkably not only in
      identifying all hemodynamic conditions, but also in quickly detecting their
      changes. On average, the networks were able to detect the hemodynamic changes in
      less than 1 s after the onset. Based on the results of this pilot investigation,
      the use of this form of TDNN to successfully predict hemodynamic conditions
      appears to be promising.

PMID- 11518669
TI  - A fuzzy sets theory application in determining the severity of respiratory
      failure.
AB  - This paper proposes to apply the theory of fuzzy sets in determining the severity
      of respiratory distress of a patient in an intensive care unit. The problem is
      modelled as a fuzzy multicriteria decision-making one. Theoretical approaches to
      the situation are considered. The proposed fuzzy selection method, based on the
      usage of the fuzzy intervals, is described. An example of determining the
      severity of respiratory distress is used to illustrate the presentation. Computer
      implementation of the model is considered, and the directions for possible
      further work are pointed out.

PMID- 11518670
TI  - Finding the right decision tree's induction strategy for a hard real world
      problem.
AB  - Decision trees have been already successfully used in medicine, but as in
      traditional statistics, some hard real world problems can not be solved
      successfully using the traditional way of induction. In our experiments we tested
      various methods for building univariate decision trees in order to find the best
      induction strategy. On a hard real world problem of the Orthopaedic fracture data
      with 2637 cases, described by 23 attributes and a decision with three possible
      values, we built decision trees with four classical approaches, one hybrid
      approach where we combined neural networks and decision trees, and with an
      evolutionary approach. The results show that all approaches had problems with
      either accuracy, sensitivity, or decision tree size. The comparison shows that
      the best compromise in hard real world problem decision trees building is the
      evolutionary approach.

PMID- 11518671
TI  - Receptors and transmission in the brain-gut axis: potential for novel therapies.
      V. Fast and slow extrinsic modulation of dorsal vagal complex circuits.
AB  - Vago-vagal reflex circuits in the medulla are responsible for the smooth
      coordination of the digestive processes carried out from the oral cavity to the
      transverse colon. In this themes article, we concentrate mostly on
      electrophysiological studies concerning the extrinsic modulation of these vago
      vagal reflex circuits, with a particular emphasis on two types of modulation,
      i.e., by "fast" classic neurotransmitters and by "slow" neuromodulators. These
      examples review two of the most potent modulatory processes at work within the
      dorsal vagal complex, which have dramatic effects on gastrointestinal function.
      The reader should be mindful of the fact that many more different inputs from
      other central nervous system (CNS) loci or circulating humoral factors add to
      this complex mix of modulatory inputs. It is likely that similar long-term
      modulations of synaptic transmission occur with other neurotransmitters and may
      represent an important mechanism for the integration and regulation of neuronal
      behavior. Of course, this fact strongly militates against the success of any
      single drug or approach in the treatment of motility disorders having a CNS
      component.

PMID- 11518672
TI  - Physiology and pathophysiology of the interstitial cell of Cajal: from bench to
      bedside. I. Functional development and plasticity of interstitial cells of Cajal
      networks.
AB  - Interstitial cells of Cajal (ICC) are the pacemaker cells in gastrointestinal
      (GI) muscles. They also mediate or transduce inputs from enteric motor nerves to
      the smooth muscle syncytium. What is known about functional roles of ICC comes
      from developmental studies based on the discovery that ICC express c-kit.
      Functional development of ICC networks depends on signaling via the Kit receptor
      pathway. Immunohistochemical studies using Kit antibodies have expanded our
      knowledge about the ICC phenotype, the structure of ICC networks, the
      interactions of ICC with other cells within the tunica muscularis, and the loss
      of ICC in some motility disorders. Manipulating Kit signaling with reagents to
      block the receptor or downstream signaling pathways or by using mutant mice in
      which Kit or its ligand, stem cell factor, are defective has allowed novel
      studies of the development of these cells within the tunica muscularis and also
      allowed the study of specific functions of different classes of ICC in several
      regions of the GI tract. This article examines the role of ICC in GI motility,
      focusing on the functional development and maintenance of ICC networks in the GI
      tract and the phenotypic changes that can occur when the Kit signaling pathway is
      disrupted.

PMID- 11518673
TI  - Regulation of cholangiocyte bicarbonate secretion.
AB  - The objective of this review article is to discuss the role of secretin and its
      receptor in the regulation of the secretory activity of intrahepatic bile duct
      epithelial cells (i.e., cholangiocytes). After a brief overview of cholangiocyte
      functions, we provide an historical background for the role of secretin and its
      receptor in the regulation of ductal secretion. We review the newly developed
      experimental in vivo and in vitro tools, which lead to understanding of the
      mechanisms of secretin regulation of cholangiocyte functions. After a description
      of the intracellular mechanisms by which secretin stimulates ductal secretion, we
      discuss the heterogeneous responses of different-sized intrahepatic bile ducts to
      gastrointestinal hormones. Furthermore, we outline the role of a number of
      cooperative factors (e.g., nerves, alkaline phosphatase, gastrointestinal
      hormones, neuropeptides, and bile acids) in the regulation of secretin-stimulated
      ductal secretion. Finally, we discuss other factors that may also play an
      important role in the regulation of secretin-stimulated ductal secretion.

PMID- 11518674
TI  - Nitric oxide in gastrointestinal epithelial cell carcinogenesis: linking
      inflammation to oncogenesis.
AB  - Chronic inflammation of gastrointestinal tissues is a well-recognized risk factor
      for the development of epithelial cell-derived malignancies. Although the
      inflammatory mediators linking chronic inflammation to carcinogenesis are
      numerous, current information suggests that nitric oxide (NO) contributes to
      carcinogenesis during chronic inflammation. Inducible nitric oxide synthase
      (iNOS), expressed by both macrophages and epithelial cells during inflammation,
      generates the bioreactive molecule NO. In addition to causing DNA lesions, NO can
      directly interact with proteins by nitrosylation and nitosation reactions. The
      consequences of protein damage by NO appear to be procarcinogenic. For example,
      NO inhibits DNA repair enzymes such as human 8-oxodeoxyguanosine DNA glycosylase
      1 and blocks apoptosis via nitrosylation of caspases. These cellular events
      permit DNA damage to accumulate, which is required for the numerous mutations
      necessary for development of invasive cancer. NO also promotes cancer progression
      by functioning as an angiogenesis factor. Strategies to inhibit NO generation
      during chronic inflammation or to scavenge reactive nitrogen species may prove
      useful in decreasing the risk of cancer development in chronic inflammatory
      gastrointestinal diseases.

PMID- 11518675
TI  - Persistent epithelial dysfunction and bacterial translocation after resolution of
      intestinal inflammation.
AB  - Epithelial secretion may play an important role in reducing bacterial
      colonization and translocation in intestine. If so, secretory dysfunction could
      result in increased susceptibility to infection and inflammation. We investigated
      whether long-term colonic secretory dysfunction occurs after a bout of colitis
      and if this is accompanied by an increase in bacterial colonization and
      translocation. Rats were studied 6 wk after induction of colitis with
      trinitrobenzene sulfonic acid when inflammation had completely resolved, and
      epithelial permeability was normal. Intestinal loops were stimulated with either
      Clostridium difficile toxin A or a phosphodiesterase inhibitor. In vitro, colonic
      tissue from previously sensitized rats was exposed to antigen (ovalbumin).
      Secretory responses to all three stimuli were suppressed in rats that had
      previously had colitis. These rats exhibited increased (16-fold) numbers of
      colonic aerobic bacteria and increased (>3-fold) bacterial translocation, similar
      to results in rats studied after resolution of enteritis. Postcolitis bacterial
      translocation was prevented by daily treatment with an inhibitor of inducible
      nitric oxide synthase. This study demonstrates that intestinal inflammation
      results in prolonged impairment of colonic epithelial secretion, which may
      contribute to increases in bacterial load and bacterial translocation. Epithelial
      dysfunction of this type could underlie an increased propensity for further bouts
      of inflammation, a hallmark of diseases such as inflammatory bowel disease.

PMID- 11518676
TI  - Glutamine transporter in crypts compensates for loss of villus absorption in
      bovine cryptosporidiosis.
AB  - Cryptosporidium parvum infection represents a significant cause of diarrhea in
      humans and animals. We studied the effect of luminally applied glutamine and the
      PG synthesis inhibitor indomethacin on NaCl absorption from infected calf ileum
      in Ussing chambers. Infected ileum displayed a decrease in both mucosal surface
      area and NaCl absorption. Indomethacin and glutamine or its stable derivative
      alanyl-glutamine increased the net absorption of Na(+) in infected tissue in an
      additive manner and to a greater degree than in controls. Immunohistochemical and
      Western blot studies showed that in control animals neutral amino acid transport
      system ASC was present in villus and crypts, whereas in infected animals, ASC was
      strongly present only on the apical border of crypts. These results are
      consistent with PGs mediating the altered NaCl and water absorption in this
      infection. Our findings further illustrate that the combined use of a PG
      synthesis inhibitor and glutamine can fully stimulate Na(+) and Cl(-) absorption
      despite the severe villous atrophy, an effect associated with increased
      expression of a Na(+)-dependent amino acid transporter in infected crypts.

PMID- 11518677
TI  - NO-mesalamine protects colonic epithelial cells against apoptotic damage induced
      by proinflammatory cytokines.
AB  - The activation of a self-amplifying cascade of caspases, of which caspase-8 is
      the apical protease, mediates Fas-, tumor necrosis factor (TNF)-related apoptosis
      inducing ligand (TRAIL)-, and TNF-alpha-induced apoptosis in colon cell lines.
      Nitric oxide (NO) protects from apoptosis induced by Fas and TNF-alpha. We
      examined whether NCX-456, an NO-releasing derivative of mesalamine, protects
      colon epithelial cells from cytokine-induced apoptosis. Caco-2 and HT-29 cell
      lines express death factor receptors and are driven to apoptosis in response to
      incubation with Fas-agonistic antibody, TNF-alpha/interferon-gamma, and TRAIL.
      The two novel observations reported here are that 1) cotreatment of cells with
      NCX-456, but not mesalamine, resulted in concentration-dependent protection
      against death factor-induced apoptosis and inhibition of caspase activity, and 2)
      exposure to dithiothreitol, an agent that effectively removes NO from thiol
      groups, resulted in a 70% recovery of caspase activity, which is consistent with
      S-nitrosation as a major mechanism for caspase inactivation. These data suggest
      that caspase S-nitrosation represents a mechanism for protection of colonic
      mucosal epithelial cells from death factor-induced death.

PMID- 11518678
TI  - GLUT-5 expression in neonatal rats: crypt-villus location and age-dependent
      regulation.
AB  - The rat fructose transporter normally appears after completion of weaning but can
      be precociously induced by early feeding of a high-fructose diet. In this study,
      the crypt-villus site, the metabolic nature of the signal, and the age dependence
      of induction were determined. In weaning rats fed high-glucose pellets, GLUT-5
      mRNA expression was modest, localized mainly in the upper three-fourths of the
      villus, and there was little expression in the villus base. When fed high
      fructose pellets, GLUT-5 mRNA expression was two to three times greater in all
      regions except the villus base. Intestinal perfusion in vivo of a
      nonmetabolizable fructose analog, 3-O-methylfructose, tended to increase fructose
      uptake rate and moderately increased GLUT-5 mRNA abundance but had no effect on
      glucose uptake rates and SGLT1 mRNA abundance. Gavage feeding of high-fructose,
      but not high-glucose, solutions enhanced fructose uptake only in pups > or =14
      days, suggesting that GLUT-5 regulation is markedly age dependent. Fructose or
      its metabolites upregulate GLUT-5 expression in all enterocytes, except those in
      the crypt and villus base and in pups <14 days old.

PMID- 11518679
TI  - HCl causes less intracellular acidification in Necturus gastric mucosa surface
      epithelial cells than other acids.
AB  - Luminal acid causes intracellular acidification in the gastric epithelium, but
      the mechanism by which H(+) enters surface cells remains obscure. This study
      addressed the problem by assessing how different acids affect intracellular pH in
      gastric surface cells. Isolated Necturus maculosus antral mucosa was exposed to
      HCl, HNO(3), H(2)SO(4), and H(3)PO(4) at pH 2.30. Intracellular pH was measured
      with microelectrodes. The physicochemical interaction of a synthetic model of
      gastric phospholipids with the different acids was studied using Langmuir film
      balance. Exposure to luminal HNO(3), H(2)SO(4), or H(3)PO(4) caused significantly
      larger intracellular acidification than exposure to HCl. The degree of
      acidification was not dependent on the valence or nature of the anionic
      counterion of the acid but significantly correlated with the amount of molecular
      acid. By Langmuir film balance, subphases acidified with HNO(3), H(2)SO(4), or
      H(3)PO(4) caused more close packing of phospholipid molecules than those
      acidified with HCl, possibly allowing hydrogen bonding between head groups to
      facilitate H(+) movement across the phospholipid membrane. HCl causes
      significantly less intracellular acidification in gastric epithelium than HNO(3),
      H(2)SO(4), or H(3)PO(4). This may be caused by the lower amount of molecular HCl
      in solution and possible hydrogen bonding between the head groups of phospholipid
      molecules and the other acids.

PMID- 11518680
TI  - Proliferation, not apoptosis, alters epithelial cell migration in small intestine
      of CFTR null mice.
AB  - Expression of a mutated cystic fibrosis transmembrane conductance regulator
      (CFTR) has been shown to enhance proliferation within CF airways, and cells
      expressing a mutated CFTR have been shown to be less susceptible to apoptosis.
      Because the CFTR is expressed in the epithelial cells lining the gastrointestinal
      tract and all CF mouse models are characterized by gastrointestinal obstruction,
      we hypothesized that CFTR null mice would have increased epithelial cell
      proliferation and reduced apoptosis within the small intestine. The rate of
      intestinal epithelial cell migration from crypt to villus was increased in CFTR
      null mice relative to mice expressing the wild-type CFTR. This difference in
      migration could be explained by an increase in epithelial cell proliferation but
      not by a difference in apoptosis within the crypts of Lieberkuhn. In addition,
      using two independent sets of CF cell lines, we found that epithelial cell
      susceptibility to apoptosis was unrelated to the presence of a functional CFTR.
      Thus increased proliferation but not alterations in apoptosis within epithelial
      cells might contribute to the pathophysiology of CF.

PMID- 11518681
TI  - Cyclooxygenase-2 downregulates inducible nitric oxide synthase in rat intestinal
      epithelial cells.
AB  - Cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression
      has been demonstrated in inflamed intestinal mucosa. Although regulation of COX-2
      and iNOS expression has been studied extensively, the interplay between these two
      enzymes remains unclear. Because they play crucial roles in inflammation and/or
      carcinogenesis, we investigated whether COX-2 regulates iNOS expression and
      evaluated the effects of COX-2 inhibitor and arachidonic acid (AA) on iNOS
      induction. The COX-2 gene coding region was stably transfected into rat
      intestinal epithelial cells (RIE sense cells). After interferon-gamma (IFN-gamma)
      and lipopolysaccharide (LPS) administration, iNOS and COX-2 expression was
      evaluated by Western blotting. PGE(2) was measured by the enzyme immunoassay
      (EIA) method. Expression of IFN response factor-1, phosphorylated extracellular
      signal-related kinase-1 and -2, and Ikappa-Balpha was evaluated. Activator
      protein-1 and nuclear factor-kappaB (NF-kappaB) were examined by gel mobility
      shift assay; a supershift assay was performed to identify the NF-kappaB complex
      components. JTE-522 or AA was added before IFN-gamma and LPS administration, and
      effects on iNOS and PGE(2) induction were evaluated by Western blotting or EIA.
      iNOS protein and mRNA expression was inhibited in RIE sense cells. Although NF
      kappaB activation was suppressed and Ikappa-Balpha protein was more stable,
      respectively, in RIE sense cells, no difference was noted in other transcription
      factors. JTE-522 increased iNOS protein expression in RIE cells. We conclude that
      COX-2 suppressed iNOS expression in RIE cells through suppression of NF-kappaB by
      stabilizing Ikappa-Balpha.

PMID- 11518682
TI  - Intestinal peptide transport: ex vivo uptake studies and localization of peptide
      carrier PEPT1.
AB  - The nature of protein breakdown products and peptidomimetic drugs such as beta
      lactams is crucial for their transmembrane transport across apical enterocyte
      membranes, which is accomplished by the pH-dependent high-capacity oligopeptide
      transporter PEPT1. To visualize oligopeptide transporter-mediated uptake of
      oligopeptides, an ex vivo assay using the fluorophore-conjugated dipeptide
      derivative D-Ala-Lys-N(epsilon)-7-amino-4-methylcoumarin-3-acetic acid (D-Ala-Lys
      AMCA) was established in the murine small intestine and compared with
      immunohistochemistry for PEPT1 in murine and human small intestine. D-Ala-Lys
      AMCA was accumulated by enterocytes throughout all segments of the murine small
      intestine, with decreasing intensity from the top to the base of the villi.
      Goblet cells did not show specific uptake. Inhibition studies revealed
      competitive inhibition by the beta-lactam cefadroxil, the angiotensin-converting
      enzyme inhibitor captopril, and the dipeptide glycyl-glutamine. Controls were
      performed using either the inhibitor diethylpyrocarbonate or an incubation
      temperature of 4 degrees C to exclude unspecific uptake. Immunohistochemistry for
      PEPT1 localized immunoreactivity to the enterocytes, with the highest intensity
      at the apical membrane. This is the first study that visualizes dipeptide
      transport across the mammalian intestine and indicates that uptake assays using D
      Ala-Lys-AMCA might be useful for characterizing PEPT1-specific substrates or
      inhibitors.

PMID- 11518683
TI  - Neutrophil-mediated epithelial injury during transmigration: role of elastase.
AB  - Neutrophil-mediated injury to gut epithelium may lead to disruption of the
      epithelial barrier function with consequent organ dysfunction, but the mechanisms
      of this are incompletely characterized. Because the epithelial apical junctional
      complex, comprised of tight and adherens junctions, is responsible in part for
      this barrier function, we investigated the effects of neutrophil transmigration
      on these structures. Using a colonic epithelial cell line, we observed that
      neutrophils migrating across cell monolayers formed clusters that were associated
      with focal epithelial cell loss and the creation of circular defects within the
      monolayer. The loss of epithelial cells was partly attributable to neutrophil
      derived proteases, likely elastase, because it was prevented by elastase
      inhibitors. Spatially delimited disruption of epithelial junctional complexes
      with focal loss of E-cadherin, beta-catenin, and zonula occludens 1 was observed
      adjacent to clusters of transmigrating neutrophils. During neutrophil
      transmigration, fragments of E-cadherin were released into the apical
      supernatant, and inhibitors of neutrophil elastase prevented this proteolytic
      degradation. Addition of purified leukocyte elastase also resulted in release of
      E-cadherin fragments, but only after opening of tight junctions. Taken together,
      these data demonstrate that neutrophil-derived proteases can mediate spatially
      delimited disruption of epithelial apical junctions during transmigration. These
      processes may contribute to epithelial loss and disruption of epithelial barrier
      function in inflammatory diseases.

PMID- 11518684
TI  - Identification of a VIP-specific receptor in guinea pig tenia coli.
AB  - Vasoactive intestinal polypeptide (VIP) and pituitary adenylate cyclase
      activating peptide (PACAP) interact with VPAC(2) receptors in rabbit and guinea
      pig (GP) gastric muscle but with functionally distinct VIP and PACAP receptors in
      GP tenia coli. This study examined whether selectivity for VIP was determined by
      two residues (40, 41) in the extracellular domain that differ in the VIP
      receptors of GP gastric and tenial muscle. A mutant rat VPAC(2) receptor (L40F,
      L41F), and two chimeric receptors in which the NH(2)-terminal domain of rat
      VPAC(2) receptor was replaced with that of GP gastric (chimeric-G) or tenia coli
      (chimeric-T) VIP receptors, were constructed and expressed in COS-1 cells. VIP
      and PACAP bound with equal affinity to wild-type and mutant rat VPAC(2) receptors
      and to chimeric-G receptor (IC(50): VIP 0.3 +/- 0.1 to 1.5 +/- 0.4 nM, PACAP 0.4
      +/- 0.1 to 2.5 +/- 0.1 nM) and stimulated cAMP with equal potency (EC(50): VIP 13
      +/- 5 to 48 +/- 8 nM, PACAP 8 +/- 3 to 31 +/- 14 nM). VIP bound with high
      affinity also to chimeric-T receptor (IC(50): 0.5 +/- 0.1 nM) and stimulated cAMP
      with high potency (EC(50): 3 +/- 1 nM). In contrast, PACAP exhibited >1,000-fold
      less affinity for binding or potency for stimulating cAMP. We conclude that GP
      tenia coli express a VIP-specific receptor and that selectivity is determined by
      a pair of extracellular phenylalanine residues.

PMID- 11518685
TI  - Helicobacter pylori lipopolysaccharide induces apoptosis of cultured guinea pig
      gastric mucosal cells.
AB  - Helicobacter pylori lipopolysaccharide (LPS) is generally accepted as a low
      toxicity virulence. Primary cultures of guinea pig gastric mucosal cells
      expressed the Toll-like receptor 4 and were sensitive to H. pylori LPS as well as
      Escherichia coli LPS. H. pylori LPS stimulated phosphorylation of transforming
      growth factor-beta-activated kinase 1 (TAK1), TAK1-binding protein 1 (TAB1), and
      c-Jun NH(2)-terminal kinase (JNK) 2. H. pylori LPS at >2.1 endotoxin unit/ml (>1
      ng/ml) activated caspase-8, stimulated cytochrome c release from mitochondria,
      and subsequently activated caspases-9 and -3, leading to apoptosis. Epidermal
      growth factor blocked all of these apoptotic processes and inhibited apoptosis,
      whereas it did not modify the phosphorylation of TAK1, TAB1, and JNK2. A
      comparatively specific inhibitor of caspase-8 or -9 blocked apoptosis, whereas
      cytochrome c release was prevented only with a caspase-8-like inhibitor. Our
      results suggest that caspase-8 and mitochondria may play crucial roles in H.
      pylori LPS-induced apoptosis and that this accelerated apoptosis may be involved
      in abnormal cell turnover of H. pylori-infected gastric mucosa.

PMID- 11518686
TI  - Gastrin induces CXC chemokine expression in gastric epithelial cells through
      activation of NF-kappaB.
AB  - Although hypergastrinemia is frequently observed in individuals with a chronic
      Helicobacter pylori infection, its pathophysiological significance in gastric
      mucosal inflammation is unclear. The present study was designed to determine if
      gastrin induces the expression of CXC chemokines in gastric epithelial cells.
      Human and rat gastric epithelial cells, transfected with gastrin receptor, were
      stimulated with gastrin. The expression of mRNAs for human interleukin-8 (IL-8)
      and rat cytokine-induced neutrophil chemoattractant-1 and release of human IL-8
      protein were then determined by Northern blot analysis and ELISA, respectively.
      Gastrin not only induced the expression of mRNAs for these chemokines but also
      stimulated IL-8 protein release. A luciferase assay using IL-8 promoter genes
      showed that nuclear factor (NF)-kappaB is absolutely required and activator
      protein-1 (AP-1) is partly required for the maximum induction of IL-8 by gastrin.
      An electrophoretic mobility shift assay revealed that gastrin is capable of
      activating both NF-kappaB and AP-1. In addition, the inhibition of NF-kappaB
      abrogated gastrin-induced chemokine expression. These results suggest that
      gastrin is capable of upregulating CXC chemokines in gastric epithelial cells and
      therefore may contribute to the progression of the inflammatory process in the
      stomach.

PMID- 11518687
TI  - Sustained esophageal contraction: a motor correlate of heartburn symptom.
AB  - Heartburn occurs in the presence as well as the absence of acid reflux. We
      searched for a motor correlate of heartburn. Twelve subjects with heartburn were
      studied with 24-h synchronized pressure, pH, and high-frequency intraluminal
      ultrasound (HFIUS) imaging of the esophagus. The HFIUS images were analyzed every
      2 s for a period of 2 min before and 30 s after the onset of heartburn during 20
      acid reflux-positive and 20 acid reflux-negative heartburn episodes. The
      esophageal muscle thickness was measured as a marker of contraction. Esophageal
      pressure and HFIUS images were recorded during the Bernstein test in 15 subjects.
      Sustained esophageal contractions (SECs) were identified during 13 of 20
      heartburn episodes associated with acid reflux and 15 of 20 heartburn episodes
      without acid reflux. SECs were detected during 2 of 40 matched control periods
      only (P < 0.05). The duration of SECs was 44.9 +/- 26.9 s. The Bernstein test
      reproduced heartburn symptoms in 8 of 15 subjects. SECs were identified during 6
      of 8 (75%) Bernstein-positive and in 1 of 7 (14.3%) Bernstein-negative tests (P =
      0.04). We conclude that a SEC precedes both spontaneous and induced heartburn
      symptoms and may be the cause of heartburn sensation.

PMID- 11518688
TI  - Inhibition of gastric emptying by acarbose is correlated with GLP-1 response and
      accompanied by CCK release.
AB  - We investigated the effect of acarbose, an alpha-glucosidase and pancreatic alpha
      amylase inhibitor, on gastric emptying of solid meals of varying nutrient
      composition and plasma responses of gut hormones. Gastric emptying was determined
      with scintigraphy in healthy subjects, and all studies were performed with and
      without 100 mg of acarbose, in random order, at least 1 wk apart. Acarbose did
      not alter the emptying of a carbohydrate-free meal, but it delayed emptying of a
      mixed meal and a carbohydrate-free meal given 2 h after sucrose ingestion. In
      meal groups with carbohydrates, acarbose attenuated responses of plasma insulin
      and glucose-dependent insulinotropic polypeptide (GIP) while augmenting responses
      of CCK, glucagon-like peptide-1 (GLP-1), and peptide YY (PYY). With mixed meal +
      acarbose, area under the curve (AUC) of gastric emptying was positively
      correlated with integrated plasma response of GLP-1 (r = 0.68, P < 0.02). With
      the carbohydrate-free meal after sucrose and acarbose ingestion, AUC of gastric
      emptying was negatively correlated with integrated plasma response of GIP,
      implying that prior alteration of carbohydrate absorption modifies gastric
      emptying of a meal. The results demonstrate that acarbose delays gastric emptying
      of solid meals and augments release of CCK, GLP-1, and PYY mainly by
      retarding/inhibiting carbohydrate absorption. Augmented GLP-1 release by acarbose
      appears to play a major role in the inhibition of gastric emptying of a mixed
      meal, whereas CCK and PYY may have contributory roles.

PMID- 11518689
TI  - Helicobacter-induced inflammatory bowel disease in IL-10- and T cell-deficient
      mice.
AB  - Inflammatory bowel disease (IBD) is thought to result from a dysregulated mucosal
      immune response to luminal microbial antigens, with T lymphocytes mediating the
      colonic pathology. Infection with Helicobacter spp has been reported to cause IBD
      in immunodeficient mice, some of which lack T lymphocytes. To further understand
      the role of T cells and microbial antigens in triggering IBD, we infected
      interleukin (IL)-10(-/-), recombinase-activating gene (Rag)1(-/-), T-cell
      receptor (TCR)-alpha(-/-), TCR-beta(-/-), and wild-type mice with Helicobacter
      hepaticus or Helicobacter bilis and compared the histopathological IBD phenotype.
      IL-10(-/-) mice developed severe diffuse IBD with either H. bilis or H.
      hepaticus, whereas Rag1(-/-), TCR-alpha(-/-), TCR-beta(-/-), and wild-type mice
      showed different susceptibilities to Helicobacter spp infection. Proinflammatory
      cytokine mRNA expression was increased in the colons of Helicobacter-infected IL
      10(-/-) and TCR-alpha(-/-) mice with IBD. These results confirm and extend the
      role of Helicobacter as a useful tool for investigating microbial-induced IBD and
      show the importance, but not strict dependence, of T cells in the development of
      bacterial-induced IBD.

PMID- 11518690
TI  - Time-dependent intestinal adaptation and GLP-2 alterations after small bowel
      resection in rats.
AB  - Existing data on morphological adaptation after small bowel resection are
      obtained by potentially biased methods. Using stereological techniques, we
      examined segments of bowel on days 0, 4, 7, 14, and 28 after 80% jejunoileal
      resection or sham operation in rats and correlated intestinal growth with plasma
      levels of glucagon-like peptide-2 (GLP-2). In the jejunum and ileum of the
      resected rats, the mucosal weight increased by 120 and 115% during the first
      week, and the weight of muscular layer increased by 134 and 83%, compared with
      sham-operated controls. The luminal surface area increased by 190% in the jejunum
      and by 155% in the ileum after 28 days. The GLP-2 level was increased by 130%
      during the entire study period in the resected rats. Small bowel resection caused
      a pronounced and persistent transmural growth response in the remaining small
      bowel, with the most prominent growth occurring in the jejunal part. The
      significantly elevated GLP-2 level is consistent with an important role of GLP-2
      in the adaptive response.

PMID- 11518691
TI  - Phosphatidylinositol is essential determinant for K+ permeability involved in
      gastric proton pumping.
AB  - Gastric vesicles purified from acid-secreting rabbit stomach display K(+)
      permeability manifested by the valinomycin-independent proton pumping of H(+)
      K(+)-ATPase as monitored by acridine orange quenching. This apparent K(+)
      permeability is attenuated by the treatment of the membrane with 5 mM Mg(2+), and
      this phenomenon has been attributed to membrane-bound phosphoprotein phosphatase.
      However, with the exception of the nonspecific inhibitor pyrophosphate, protein
      phosphatase inhibitors failed to inhibit the loss of K(+) permeability.
      Preincubation of the membrane with neomycin, a phospholipase C inhibitor,
      surrogated the effect of Mg(2+), whereas another inhibitor, U-73122, did not.
      Phosphatidylinositol 4,5-bisphosphate (PIP(2)) restored the attenuated K(+)
      permeability by treatment with either Mg(2+) or neomycin. Furthermore, either
      phosphatidylinositol bound to phosphatidylinositol transfer protein or
      phosphatidylinositol 4,5,6-trisphosphate (PIP(3)) surrogated the effect of
      PIP(2). Mg(2+) and neomycin reduced K(+) permeability in the membrane as
      determined by Rb(+) influx and K(+)-dependent H(+) diffusion. Treatment with
      Mg(2+) reduced the contents of PIP(2) and PIP(3) in the membrane. These results
      suggest that PIP(2) and/or PIP(3) maintain K(+) permeability, which is essential
      for proton pumping in the apical membrane of the secreting parietal cell.

PMID- 11518692
TI  - Changes in serotonin levels and 5-HT receptor activity in duodenum of
      streptozotocin-diabetic rats.
AB  - Few previous studies have discussed the changes in serotonin receptor activity in
      the small intestine of diabetic animals. Therefore, we examined serotonin content
      in duodenal tissue and dose-dependent effects of serotonin agonists and
      antagonists on the motor activity of ex vivo vascularly perfused duodenum of
      streptozotocin (STZ)-diabetic rats. Serotonin content was significantly increased
      in enterochromaffin cells but not altered in serotonin-containing neurons in STZ
      diabetic rats. Motor activity assessed by frequency, amplitude, and percent
      motility index per 10 min of pressure waves was reduced in the duodenum of
      diabetic rats, and this reduction was reversed by insulin treatment. Serotonin
      dose dependently increased the motor activity in control rat duodenum but only a
      higher concentration of serotonin increased the motor activity in diabetic rats.
      The 5-hydroxytryptamine (5-HT) receptor subtype 4 (5-HT(4)) antagonist SB-204070
      dose dependently reduced motor activity in both control and diabetic rats,
      whereas the 5-HT(3) receptor antagonist azasetron, even at a higher
      concentration, failed to affect motor activity in diabetic rat duodenum but dose
      dependently reduced motor activity in control rat duodenum. These results suggest
      that 5-HT(3) receptor activity was impaired but 5-HT(4) receptor activity was
      intact in STZ-diabetic rat duodenum. Such an impairment of 5-HT(3) receptor
      activity may induce the motility disturbance in the small intestine of diabetes
      mellitus.

PMID- 11518693
TI  - Cold preservation-warm reoxygenation increases hepatocyte steady-state Ca(2+) and
      response to Ca(2+)-mobilizing agonist.
AB  - Although the role of Ca(2+) in liver transplantation injury has been the object
      of several studies, direct evidence for alterations in intracellular Ca(2+)
      homeostasis after cold preservation-warm reoxygenation (CP/WR) has never been
      presented. We thus investigated the effects of CP/WR on steady-state Ca(2+) and
      responses to a Ca(2+)-mobilizing agonist. Isolated rat hepatocytes were suspended
      in University of Wisconsin solution, stored at 4 degrees C for 0, 24, and 48 h,
      and reoxygenated at 37 degrees C for 1 h. Cytosolic Ca(2+) was measured in single
      cells by digitized fluorescence videomicroscopy. CP/WR caused a significant
      increase in steady-state cytosolic Ca(2+), which was inversely proportional to
      cell viability. Pretreatment of hepatocytes with an agent that protects
      mitochondrial function attenuated the increase in steady-state cytosolic Ca(2+)
      and improved hepatocyte viability. Ca(2+) responses to the purinergic agonist ATP
      also increased significantly as a function of cold storage time. This increase
      was related to an increase in the size of inositol 1,4,5-trisphosphate-sensitive
      Ca(2+) stores and subsequent capacitative Ca(2+) entry. Thus CP/WR significantly
      perturbs steady-state hepatocellular Ca(2+) and responses to Ca(2+)-mobilizing
      agonists, which may contribute to hepatocyte metabolic dysfunction observed after
      CP/WR.

PMID- 11518694
TI  - Spontaneous water secretion in T84 cells: effects of STa enterotoxin, bumetanide,
      VIP, forskolin, and A-23187.
AB  - The regulated Cl(-) secretory apparatus of T84 cells responds to several
      pharmacological agents via different second messengers (Ca(2+), cAMP, cGMP).
      However, information about water movements in T84 cells has not been available.
      In the absence of osmotic or chemical gradient, we observed a net secretory
      transepithelial volume flux (J(w) = -0.16 +/- 0.02 microl.min(-1).cm(-2)) in
      parallel with moderate short-circuit current values (I(sc) = 1.55 +/- 0.23
      microA/cm(2)). The secretory J(w) reversibly reverted to an absorptive value when
      A-23187 was added to the serosal bath. Vasoactive intestinal polypeptide
      increased I(sc), but, unexpectedly, J(w) was not affected. Bumetanide, an
      inhibitor of basolateral Na(+)-K(+)-2Cl(-) cotransporter, completely blocked
      secretory J(w) with no change in I(sc). Conversely, serosal forskolin increased
      I(sc), but J(w) switched from secretory to absorptive values. Escherichia coli
      heat-stable enterotoxin increased secretory J(w) and I(sc). No difference between
      the absorptive and secretory unidirectional Cl(-) fluxes was observed in basal
      conditions, but after STa stimulation, a significant net secretory Cl(-) flux
      developed. We conclude that, under these conditions, the presence of secretory or
      absorptive J(w) values cannot be shown by I(sc) and ion flux studies.
      Furthermore, RT-PCR experiments indicate that aquaporins were not expressed in
      T84 cells. The molecular pathway for water secretion appears to be transcellular,
      moving through the lipid bilayer or, as recently proposed, through water-solute
      cotransporters.

PMID- 11518695
TI  - Epithelial and bacterial metalloproteinases and their inhibitors in H. pylori
      infection of human gastric cells.
AB  - To test the hypothesis that Helicobacter pylori regulates gastric cell secretion
      of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases
      (TIMPs), culture media from infected and uninfected human gastric adenocarcinoma
      (AGS) cells were analyzed by zymography, MMP activity assays, and immunoblotting.
      AGS cells secreted gelatinolytic (prominently 90 kDa) and caseinolytic (110 kDa)
      activity together with MMP-1, MMP-3, and TIMP-1, TIMP-2, and TIMP-3 isoforms. H.
      pylori secreted caseinolytic activity (60 kDa), MMP-3-like enzyme activity, and
      TIMP-3 immunoreactivity. H. pylori infection increased the 110-kDa caseinolytic
      activity and induced new gelatinolytic (~35 kDa) and caseinolytic (22 kDa)
      activities. Infection also increased both basal secretion and activation of MMP-1
      and MMP-3, enhanced TIMP-3 secretion, and increased the formation of MMP-3/TIMP-3
      complexes. TIMP-1 and TIMP-2 secretion were unchanged. Normal AGS cells showed a
      pancellular distribution of TIMP-3, with redistribution of immunoreactivity
      toward sites of bacterial attachment after H. pylori infection. The data indicate
      that MMP and TIMP secretion by AGS cells is modulated by H. pylori infection and
      that host MMP-3 and a TIMP-3 homolog expressed by H. pylori mediate at least part
      of the host cell response to infection.

PMID- 11518696
TI  - PKC-beta1 mediates EGF protection of microtubules and barrier of intestinal
      monolayers against oxidants.
AB  - Using monolayers of human intestinal (Caco-2) cells, we found that oxidants and
      ethanol damage the cytoskeleton and disrupt barrier integrity; epidermal growth
      factor (EGF) prevents damage by enhancement of protein kinase C (PKC) activity
      and translocation of the PKC-beta1 isoform. To see if PKC-beta1 mediates EGF
      protection, cells were transfected to stably over- or underexpress PKC-beta1.
      Transfected monolayers were preincubated with low or high doses of EGF (1 or 10
      ng/ml) or 1-oleoyl-2-acetyl-sn-glycerol [OAG; a PKC activator (0.01 or 50
      microM)] before treatment with oxidant (0.5 mM H(2)O(2)). Only in monolayers
      overexpressing PKC-beta1 (3.1-fold) did low doses of EGF or OAG initiate
      protection, increase tubulin polymerization (assessed by quantitative
      immunoblotting) and microtubule architectural integrity (laser scanning confocal
      microscopy), maintain normal barrier permeability (fluorescein sulfonic acid
      clearance), and cause redistribution of PKC-beta1 from cytosolic pools into
      membrane and/or cytoskeletal fractions (assessed by immunoblotting), thus
      indicating PKC-beta1 activation. Antisense inhibition of PKC-beta1 expression (
      90%) prevented these changes and abolished EGF protection. We conclude that EGF
      protection against oxidants requires PKC-beta1 isoform activation. This mechanism
      may be useful for development of novel therapies for the treatment of
      inflammatory gastrointestinal disorders including inflammatory bowel disease.

PMID- 11518697
TI  - Mice with combined disruption of Gpx1 and Gpx2 genes have colitis.
AB  - Glutathione peroxidase (GPX)-1 and gastrointestinal (GI) epithelium-specific GPX
      (GPX-GI), encoded by Gpx1 and Gpx2, provide most GPX activity in GI epithelium.
      Although homozygous mice deficient in either the Gpx1 or Gpx2 gene appeared to be
      normal under standard housing conditions, homozygous mice deficient in both
      genes, double-knockout (KO) mice, had symptoms and pathology consistent with
      inflammatory bowel disease. These symptoms included a high incidence of perianal
      ulceration, growth retardation that started around weaning, and hypothermia that
      resembled that observed in calorie-restricted mice, even though the double-KO
      mice in our study were allowed to eat ad libitum. The growth retardation and
      hypothermia were components of cachexia, which is fatal in a high percentage of
      mice. Histological examination revealed that the double-KO mice had a high
      incidence of mucosal inflammation in the ileum and colon but not in the jejunum.
      Elevated levels of myeloperoxidase activity and lipid hydroperoxides were also
      detected in colon mucosa of these homozygous double-KO mice. These results
      suggest that GPX is essential for the prevention of the inflammatory response in
      intestinal mucosa.

PMID- 11518698
TI  - Aquaporin-2, a regulated water channel, is expressed in apical membranes of rat
      distal colon epithelium.
AB  - Aquaporin-2 (AQP-2) is the vasopressin-regulated water channel expressed in the
      apical membrane of principal cells in the collecting duct and is involved in the
      urinary concentrating mechanism. In the rat distal colon, vasopressin stimulates
      water absorption through an unknown mechanism. With the hypothesis that AQP-2
      could contribute to this vasopressin effect, we studied its presence in rat
      colonic epithelium. We used RT-PCR, in situ hybridization, immunoblotting, and
      immunocytochemistry to probe for AQP-2 expression. An AQP-2 amplicon was obtained
      through RT-PCR of colon epithelium RNA, and in situ hybridization revealed AQP-2
      mRNA in colonic crypts and, to a lesser extent, in surface absorptive epithelial
      cells. AQP-2 protein was localized to the apical membrane of surface absorptive
      epithelial cells, where it colocalized with H(+)-K(+)-ATPase but not with Na(+)
      K(+)-ATPase. AQP-2 was absent from the small intestine, stomach, and liver. Water
      deprivation increased the hybridization signal and the protein level (assessed by
      Western blot analysis) for AQP-2 in distal colon. This was accompanied by
      increased p-chloromercuriphenylsulfonic acid-sensitive water absorption. These
      results indicate that AQP-2 is present in the rat distal colon, where it might be
      involved in a water-sparing mechanism. In addition, these results support the
      idea that AQP-2, and probably other aquaporins, are involved in water absorption
      in the colon.

PMID- 11518699
TI  - Regulation of transcription by AMP-activated protein kinase: phosphorylation of
      p300 blocks its interaction with nuclear receptors.
AB  - AMP-activated protein kinase (AMP-kinase) modulates many metabolic processes in
      response to fluctuations in cellular energy status. Although most of its known
      targets are metabolic enzymes, it has been proposed that AMP-kinase might also
      regulate gene expression. Here we demonstrate that the transcriptional
      coactivator p300 is a substrate of AMP-kinase. Phosphorylation of p300 at serine
      89 by AMP-kinase dramatically reduced its interaction, in vitro and in vivo, with
      the nuclear receptors peroxisome proliferator-activated receptor gamma, thyroid
      receptor, retinoic acid receptor, and retinoid X receptor, but did not affect its
      interaction with the non-nuclear receptor transcription factors E1a, p53, or
      GATA4. These findings indicate that the AMP-kinase signaling pathway selectively
      modulates a subset of p300 activities and represent the first example of a
      transcriptional component regulated by AMP-kinase. Our results suggest a direct
      link between cellular energy metabolism and gene expression.

PMID- 11518700
TI  - Redox regulation of the rotation of F(1)-ATP synthase.
AB  - In F(1)-ATPase, the smallest known motor enzyme, unidirectional rotation of the
      central axis subunit gamma is coupled to ATP hydrolysis. In the present study, we
      report the redox switching of the rotation of this enzyme. For this purpose, the
      switch region from the gamma subunit of the redox-sensitive chloroplast F(1)
      ATPase was introduced into the bacterial F(1)-ATPase. The ATPase activity of the
      obtained complex was increased up to 3-fold upon reduction (Bald, D., Noji, H.,
      Stumpp, M. T., Yoshida, M. & Hisabori, T. (2000) J. Biol. Chem. 275, 12757
      12762). Here, we successfully observed the modulation of rotation of gamma in
      this chimeric complex by changes in the redox conditions. In addition we revealed
      that the suppressed enzymatic activity of the oxidized F(1)-ATPase complex was
      characterized by more frequent long pauses in the rotation of the gamma subunit.
      These findings obtained by the single molecule analysis therefore provide new
      insights into the mechanisms of enzyme regulation.

PMID- 11518701
TI  - Determining the dimensions of the drug-binding domain of human P-glycoprotein
      using thiol cross-linking compounds as molecular rulers.
AB  - The human multidrug resistance P-glycoprotein (P-gp) interacts with a broad range
      of compounds with diverse structures and sizes. There is considerable evidence
      indicating that residues in transmembrane segments 4-6 and 10-12 form the drug
      binding site. We attempted to measure the size of the drug-binding site by using
      thiol-specific methanethiosulfonate (MTS) cross-linkers containing spacer arms of
      2 to 17 atoms. The majority of these cross-linkers were also substrates of P-gp,
      because they stimulated ATPase activity (2.5- to 10.1-fold). 36 P-gp mutants with
      pairs of cysteine residues introduced into transmembrane segments 4-6 and 10-12
      were analyzed after reaction with 0.2 mm MTS cross-linker at 4 degrees C. The
      cross-linked product migrated with lower mobility than native P-gp in SDS gels.
      13 P-gp mutants were cross-linked by MTS cross-linkers with spacer arms of 9-25
      A. Vinblastine and cyclosporin A inhibited cross-linking. The emerging picture
      from these results and other studies is that the drug-binding domain is large
      enough to accommodate compounds of different sizes and that the drug-binding
      domain is "funnel" shaped, narrow at the cytoplasmic side, at least 9-25 A in the
      middle, and wider still at the extracellular surface.

PMID- 11518702
TI  - The ORF3 protein of hepatitis E virus binds to Src homology 3 domains and
      activates MAPK.
AB  - The hepatitis E virus (HEV) is the causative agent of hepatitis E, an acute form
      of viral hepatitis. The biology and pathogenesis of HEV remain poorly understood.
      We have used in vitro binding assays to show that the HEV ORF3 protein (pORF3)
      binds to a number of cellular signal transduction pathway proteins. This includes
      the protein tyrosine kinases Src, Hck, and Fyn, the p85alpha regulatory subunit
      of phosphatidylinositol 3-kinase, phospholipase Cgamma, and the adaptor protein
      Grb2. A yeast two-hybrid assay was used to further confirm the pORF3-Grb2
      interaction. The binding involves a proline-rich region in pORF3 and the src
      homology 3 (SH3) domains in the cellular proteins. Competition assays and
      computer-assisted modeling was used to evaluate the binding surfaces and
      interaction energies of the pORF3.SH3 complex. In pORF3-expressing cells,
      pp60(src) was found to associate with an 80-kDa protein, but no activation of the
      Src kinase was observed in these cells. However, there was increased activity and
      nuclear localization of ERK in the pORF3-expressing cells. These studies suggest
      that pORF3 is a viral regulatory protein involved in the modulation of cell
      signaling. The ORF3 protein of HEV appears to be the first example of a SH3
      domain-binding protein encoded by a virus that causes an acute and primarily self
      limited infection.

PMID- 11518703
TI  - Isolation and characterization of two novel forms of the human prolactin receptor
      generated by alternative splicing of a newly identified exon 11.
AB  - We have identified a novel exon 11 of the human prolactin receptor (hPRLR) gene
      that is distinct from its rodent counterparts and have demonstrated the presence
      of two novel short forms of the hPRLR (S1(a) and S1(b)), which are derived from
      alternative splicing of exons 10 and 11. S1(a) encodes 376 amino acids (aa) that
      contain partial exon 10 and a unique 39-aa C-terminal region encoded by exon 11.
      S1(b) encodes 288 aa that lack the entire exon 10 and contains 3 amino acids at
      the C terminus derived from exon 11 using a shifted reading frame. These short
      forms, which were found in several normal tissues and in breast cancer cell
      lines, were expressed as cell surface receptors and possessed binding affinities
      comparable with the long form. Unlike the long form, neither short form was able
      to mediate the activation of the beta-casein gene promoter induced by prolactin.
      Instead they acted as dominant negative forms when co-expressed with the long
      form in transfected cells. Due to a marked difference in the cellular levels
      between the two short forms in transfected cells, S1(b) was more effective in
      inhibiting the prolactin-induced activation of the beta-casein gene promoter
      mediated by the long form of the receptor. The low cellular level of S1(a) was
      due to its more rapid turnover than the S1(b) protein. This is attributable to
      specific residues within the C-terminal unique 39 amino acids of the S1(a) form
      and may represent a new mechanism by which the hPRLR is modulated at the post
      translational level. Since both short forms contain abbreviated cytoplasmic
      domains with unique C termini, they may also exhibit distinct signaling pathways
      in addition to modulating the signaling from the long form of the receptor. These
      receptors may therefore play important roles in the diversified actions of
      prolactin in human tissues.

PMID- 11518704
TI  - IRAK-mediated translocation of TRAF6 and TAB2 in the interleukin-1-induced
      activation of NFkappa B.
AB  - The interleukin-1 (IL-1) receptor-associated kinase (IRAK) is required for the IL
      1-induced activation of nuclear factor kappaB and c-Jun N-terminal kinase. The
      goal of this study was to understand how IRAK activates the intermediate proteins
      TRAF6, TAK1, TAB1, and TAB2. When IRAK is phosphorylated in response to IL-1, it
      binds to the membrane where it forms a complex with TRAF6; TRAF6 then dissociates
      and translocates to the cytosol. The membrane-bound IRAK similarly mediates the
      IL-1-induced translocation of TAB2 from the membrane to the cytosol. Different
      regions of IRAK are required for the translocation of TAB2 and TRAF6, suggesting
      that IRAK mediates the translocation of each protein separately. The
      translocation of TAB2 and TRAF6 is needed to form a TRAF6-TAK1-TAB1-TAB2 complex
      in the cytosol and thus activate TAK1. Our results show that IRAK is required for
      the IL-1-induced phosphorylation of TAK1, TAB1, and TAB2. The phosphorylation of
      these three proteins correlates strongly with the activation of nuclear factor
      kappaB but is not necessary to activate c-Jun N-terminal kinase.

PMID- 11518705
TI  - Rapid calmodulin-dependent interdomain electron transfer in neuronal nitric-oxide
      synthase measured by pulse radiolysis.
AB  - Electron transfer within rat neuronal nitric-oxide synthase (nNOS) was
      investigated by pulse radiolysis. Radiolytically generated 1-methyl-3-carbamoyl
      pyridinium (MCP) radical was found to react predominantly with the heme of the
      enzyme with a second-order rate constant for heme reduction of 3 x 10(8) m(-1) s(
      1). In the calmodulin (CaM)-bound enzyme a subsequent first-order phase was
      observed which had a rate constant of 1.2 x 10(3) s(-1). In the absence of CaM,
      this phase was absent. Kinetic difference spectra for nNOS reduction indicated
      that the second phase consisted of heme reoxidation accompanied by formation of a
      neutral flavin semiquinone, suggesting that it is heme to flavin electron
      transfer. Experiments with the heme proximal surface mutant, K423E, had no second
      phase, confirming that the mutation blocks interdomain electron transfer. With
      the autoinhibitory loop deletion mutant, Delta40, the slow phase was observed
      even in the absence of CaM consistent with the role of the loop in impeding
      interdomain electron transfer. The rate of heme to FMN electron transfer observed
      in the wild-type enzyme is approximately 1000 times faster than the FMN to heme
      electron transfer rate predicted during catalysis from kinetic modeling,
      suggesting that the catalytic process is slowed by kinetic gating.

PMID- 11518706
TI  - Accelerated s-nitrosothiol breakdown by amyotrophic lateral sclerosis mutant
      copper,zinc-superoxide dismutase.
AB  - Mutations in copper,zinc-superoxide dismutase (SOD) have been implicated in
      familial amyotrophic lateral sclerosis (FALS). We have investigated the breakdown
      of S-nitrosothiols by wild-type (WT) SOD and two common FALS mutants, alanine-4
      valine (A4V) SOD and glycine-37 arginine (G37R) SOD. In the presence of
      glutathione, A4V SOD and G37R SOD catalyzed S-nitrosoglutathione breakdown three
      times more efficiently than WT SOD. Indeed, A4V SOD catabolized GSNO more
      efficiently than WT SOD throughout the physiological range of GSH concentrations.
      Moreover, a variety of additional S-nitrosothiols were catabolized more readily
      by A4V SOD than by WT SOD. Initial rate data for fully reduced WT SOD and A4V
      SOD, and data using ascorbic acid as the reductant, suggest that FALS mutations
      in SOD may influence the efficiency of reduction of the copper center by
      glutathione. We have identified a potentially toxic gain of function of two
      common FALS mutations that may contribute to neurodegeneration in FALS.

PMID- 11518707
TI  - Capture of a dimeric intermediate during transthyretin amyloid formation.
AB  - Point mutations in the human plasma protein transthyretin are associated with the
      neurological disorder familial amyloidosis with polyneuropathy type 1. The
      disease is characterized by amyloid fibril deposits causing damage at the site of
      deposition. Substitution of two amino acids in the hydrophobic core of
      transthyretin lead to a mutant that was very prone to form amyloid. In addition,
      this mutant has also been shown to induce a toxic response on a neuroblastoma
      cell line. Renaturation of the transthyretin mutant at low temperature
      facilitated the isolation of an amyloid-forming intermediate state having the
      apparent size of a dimer. Increasing the temperature effectively enhanced the
      rate of interconversion from a partly denatured protein to mature amyloid. Using
      circular dichroism the beta-sheet content of the formed mature fibrils was
      significantly lower than that of the native fold of transthyretin. Morphology
      studies using electron microscopy also indicated a temperature-dependent
      transformation from amorphous aggregates toward mature amyloid fibrils. In
      addition, 1-anilino-8-naphtalenesulfonate fluorescence studies suggested the loss
      of the thyroxin-binding channel within both the isolated intermediate and the
      mature fibrils.

PMID- 11518708
TI  - EPR detection of glutathionyl and protein-tyrosyl radicals during the interaction
      of peroxynitrite with macrophages (J774).
AB  - Peroxynitrite is one of the biological oxidants whose addition to cells has been
      shown to either activate signaling pathways or lead to cell injury, depending on
      cell type and oxidant concentration. The intermediacy of free radicals in these
      processes has been directly demonstrated only during the interaction of
      peroxynitrite with erythrocytes, a particular cell type, due to its high
      hemoglobin content. Here, we demonstrate that the addition of peroxynitrite to a
      macrophage cell line (J774) led to the production of glutathionyl and protein
      tyrosyl radicals. The glutathionyl radical was characterized by EPR spin-trapping
      experiments with 5,5-dimethyl-1-pyrroline-N-oxide. Protein-tyrosyl radical
      formation was suggested by direct EPR spectroscopy and confirmed by EPR spin
      trapping experiments with 3,5-dibromo-4-nitrosobenzenesulfonic acid and Western
      blot analysis of nitrated proteins in treated macrophages. Time dependence
      studies of free radical formation indicate that intracellular glutathione and
      unidentified proteins are the initial peroxynitrite targets in macrophages and
      that their derived radicals trigger radical chain reactions. The results are
      likely to be relevant to the understanding of the bioregulatory and biodamaging
      effects of peroxynitrite.

PMID- 11518709
TI  - Protein kinase Dyrk1 activates cAMP response element-binding protein during
      neuronal differentiation in hippocampal progenitor cells.
AB  - Dyrk is a dual specific protein kinase thought to be involved in normal embryo
      neurogenesis and brain development. Defects/imperfections in this kinase have
      been suggested to play an important role in the mental retardation of patients
      with Down's syndrome. The transcriptional factor cAMP response element-binding
      protein (CREB) has been implicated in the formation of many types of synaptic
      plasticity, such as learning and memory. In the present study we show that Dyrk1
      activity is markedly induced during the differentiation of immortalized
      hippocampal progenitor (H19-7) cells. The addition of a neurogenic factor, basic
      fibroblast growth factor, to the H19-7 cells results in an increased specific
      binding of Dyrk1 to active CREB. In addition, Dyrk1 directly phosphorylates CREB,
      leading to the stimulation of subsequent CRE-mediated gene transcription during
      the neuronal differentiation in H19-7 cells. Blockade of Dyrk1 activation
      significantly inhibits the neurite outgrowth as well as CREB phosphorylation
      induced by basic fibroblast growth factor. These findings suggest that Dyrk1
      activation and subsequent CREB phosphorylation is important in the neuronal
      differentiation of central nervous system hippocampal cells.

PMID- 11518710
TI  - The low density lipoprotein receptor-related protein/alpha2-macroglobulin
      receptor is a receptor for connective tissue growth factor.
AB  - Connective tissue growth factor (CTGF) expression is regulated by transforming
      growth factor-beta (TGF-beta) and strong up-regulation occurs during wound
      healing; in situ hybridization data indicate that there are high levels of CTGF
      expression in fibrotic lesions. Recently the binding parameters of CTGF to both
      high and lower affinity cell surface binding components have been characterized.
      Affinity cross-linking and SDS-polyacrylamide gel electrophoresis analysis
      demonstrated the binding of CTGF to a cell surface protein with a mass of
      approximately 620 kDa. We report here the purification of this protein by
      affinity chromatography on CTGF coupled to Sepharose and sequence information
      obtained by mass spectroscopy. The binding protein was identified as the
      multiligand receptor, low density lipoprotein receptor-related protein/alpha2
      macroglobulin receptor (LRP). The identification of LRP as a receptor for CTGF
      was validated by several studies: 1) binding competition with many ligands that
      bind to LRP, including receptor-associated protein; 2) immunoprecipitation of
      CTGF-receptor complex with LRP antibodies; and 3) cells that are genetically
      deficient for LRP were unable to bind CTGF. Last, CTGF is rapidly internalized
      and degraded and this process is LRP-dependent. In summary, our data indicate
      that LRP is a receptor for CTGF, and may play an important role in mediating CTGF
      biology.

PMID- 11518711
TI  - Mutations in the INK4a/ARF melanoma susceptibility locus functionally impair
      p14ARF.
AB  - The INK4a/ARF locus encodes two cell cycle regulatory proteins, the cyclin
      dependent kinase inhibitor, p16(INK4a), and the p53 activator, p14(ARF). Germline
      mutations in this locus are associated with melanoma susceptibility in 20-40% of
      multiple case melanoma families. Many of these mutations specifically impair
      p16(INK4a), whereas mutations uniquely targeting p14(ARF) are rare. Nevertheless,
      the importance of p14(ARF) has not been excluded because more than 40% of
      INK4a/ARF alterations affect p16(INK4a) and p14(ARF). We now report that p14(ARF)
      is functionally impaired in melanoma kindreds carrying INK4a/ARF mutations. Of
      the seven INK4a/ARF mutations tested, three altered the subcellular distribution
      of p14(ARF) and diminished the ability of p14(ARF) to activate the p53 pathway.
      This work establishes the importance of p14(ARF) in melanoma predisposition.

PMID- 11518712
TI  - Accessory factors facilitate the binding of glucocorticoid receptor to the
      phosphoenolpyruvate carboxykinase gene promoter.
AB  - Glucocorticoid induction of the phosphoenolpyruvate carboxykinase (PEPCK) gene
      requires a glucocorticoid response unit (GRU) comprised of two non-consensus
      glucocorticoid receptor (GR) binding sites, GR1 and GR2, and at least three
      accessory factor elements (gAF1-3). DNA-binding accessory proteins are commonly
      required for the regulation of genes whose products play an important role in
      metabolism, development, and a variety of defense responses, but little is known
      about why they are necessary. Quantitative, real time homogenous assays of
      cooperative protein-DNA interactions in complex media (e.g. nuclear extracts)
      have not previously been reported. Here we perform quantitative, real time
      equilibrium and stopped-flow fluorescence anisotropy measurements of protein-DNA
      interactions in nuclear extracts to demonstrate that GR binds to the GR1-GR2
      elements poorly as compared with a palindromic or consensus glucocorticoid
      response element (GRE). Inclusion of either the gAF1 or gAF2 element with GR1
      GR2, however, creates a high affinity binding environment for GR. GR can undergo
      multiple rounds of binding and dissociation to the palindromic GRE in less than
      100 ms at nanomolar concentrations. The dissociation rate of GR is differentially
      slowed by the gAF1 or gAF2 elements that bind two functionally distinct accessory
      factors, COUP-TF/HNF4 and HNF3, respectively.

PMID- 11518713
TI  - Differential expression of endophilin 1 and 2 dimers at central nervous system
      synapses.
AB  - Endophilin 1 is proposed to participate in synaptic vesicle biogenesis through
      SH3 domain-mediated interactions with the polyphosphoinositide phosphatase
      synaptojanin and the GTPase dynamin. Endophilin family members have also been
      identified as binding partners for a number of diverse cellular proteins. We
      define here the endophilin 1-binding site within synaptojanin 1 and show that
      this sequence independently and selectively purifies from brain extracts
      endophilin 1 and a closely related protein, endophilin 2. Endophilin 2, like
      endophilin 1, is highly expressed in brain, concentrated in nerve terminals, and
      found in complexes with synaptojanin and dynamin. Although a fraction of
      endophilins 1 and 2 coexist in the same complex, the distribution of these
      endophilin isoforms among central synapses only partially overlaps. Endophilins 1
      and 2 are found predominantly as stable dimers through a predicted coiled-coil
      domain in their conserved NH2-terminal moiety. Dimerization may allow endophilins
      to link a number of different cellular targets to the endocytic machinery.

PMID- 11518714
TI  - Carboxyl-terminal domain III of the delta' subunit of the DNA polymerase III
      holoenzyme binds delta.
AB  - The delta and delta' subunits are essential components of the DNA polymerase III
      holoenzyme, required for assembly and function of the DnaX-complex clamp loader
      (tau2gammadeltadelta'chipsi). The x-ray crystal structure of delta' contains
      three structural domains (Guenther, B., Onrust, R., Sali, A., O'Donnell, M., and
      Kuriyan, J. (1997) Cell 91, 335-345). In this study, we localize the delta
      binding domain of delta' to a carboxyl-terminal domain III by quantifying the
      interaction of delta with a series of delta' fusion proteins lacking specific
      domains. Purification and immobilization of the fusion proteins were facilitated
      by the inclusion of a tag containing hexahistidine and a short biotinylation
      sequence. Both NH2- and COOH-terminal-tagged full-length delta' were soluble and
      had specific activities comparable with that of native delta'. delta and delta'
      form a 1:1 heterodimer with a dissociation constant (K(D)) of 5 x 10(-7) m
      determined by equilibrium sedimentation. The K(D) determined by surface plasmon
      resonance was comparable. Domain III alone bound delta at an affinity comparable
      to that of wild type delta', whereas proteins lacking domain III did not bind
      delta. Using a panel of domain-specific anti-delta' monoclonal antibodies, we
      found that two of the domain III-specific monoclonal antibodies interfered with
      delta-delta' interaction and abolished the replication activity of DNA polymerase
      III holoenzyme.

PMID- 11518715
TI  - Conserved regions 4.1 and 4.2 of sigma(70) constitute the recognition sites for
      the anti-sigma factor AsiA, and AsiA is a dimer free in solution.
AB  - The association of the bacteriophage T4-encoded AsiA protein with the final
      sigma(70) subunit of the Escherichia coli RNA polymerase is one of the principal
      events governing transcription of the T4 genome. Analytical ultracentrifugation
      and NMR studies indicate that free AsiA is a symmetric dimer and the dimers can
      exchange subunits. Using NMR, the mutual recognition sites on AsiA and final
      sigma(70) have been elucidated. Residues throughout the N-terminal half of AsiA
      are involved either directly or indirectly in binding to final sigma(70) whereas
      the two highly conserved C-terminal regions of final sigma(70), denoted 4.1 and
      4.2, constitute the entire AsiA binding domain. Peptides corresponding to these
      regions bind tightly to AsiA individually and simultaneously. Simultaneous
      binding promotes structural changes in AsiA that mimic interaction with the
      complete AsiA binding determinant of final sigma(70). Moreover, the results
      suggest that a significant rearrangement of the dimer accompanies peptide
      binding. Thus, both conserved regions 4.1 and 4.2 are intimately involved in
      recognition of AsiA by final sigma(70). The interaction of AsiA with 4.1 provides
      a potential explanation of the differential abilities of DNA and AsiA to bind to
      free final sigma(70) and a mechanistic alternative to models of AsiA function
      that rely on binding to a single site on final sigma(70).

PMID- 11518716
TI  - Three-dimensional model and characterization of the iron stress-induced CP43'
      photosystem I supercomplex isolated from the cyanobacterium Synechocystis PCC
      6803.
AB  - The cyanobacterium Synechocystis PCC 6803 has been subjected to growth under iron
      deficient conditions. As a consequence, the isiA gene is expressed, and its
      product, the chlorophyll a-binding protein CP43', accumulates in the cell.
      Recently, we have shown for the first time that 18 copies of this photosystem II
      (PSII)-like chlorophyll a-binding protein forms a ring around the trimeric
      photosystem I (PSI) reaction center (Bibby, T. S., Nield, J., and Barber, J.
      (2001) Nature, 412, 743-745). Here we further characterize the biochemical and
      structural properties of this novel CP43'-PSI supercomplex confirming that it is
      a functional unit of approximately 1900 kDa where the antenna size of PSI is
      increased by 70% or more. Using electron microscopy and single particle analysis,
      we have constructed a preliminary three-dimensional model of the CP43'-PSI
      supercomplex and used it as a framework to incorporate higher resolution
      structures of PSI and CP43 recently derived from x-ray crystallography. Not only
      does this work emphasize the flexibility of cyanobacterial light-harvesting
      systems in response to the lowering of phycobilisome and PSI levels under iron
      deficient conditions, but it also has implications for understanding the
      organization of the related chlorophyll a/b-binding Pcb proteins of
      oxychlorobacteria, formerly known as prochlorophytes.

PMID- 11518717
TI  - IGF-I receptor-induced cell-cell adhesion of MCF-7 breast cancer cells requires
      the expression of junction protein ZO-1.
AB  - Hyperactivation of the insulin-like growth factor I receptor (IGF-IR) contributes
      to primary breast cancer development, but the role of the IGF-IR in tumor
      metastasis is unclear. Here we studied the effects of the IGF-IR on intercellular
      connections mediated by the major epithelial adhesion protein, E-cadherin (E
      cad). We found that IGF-IR overexpression markedly stimulated aggregation in E
      cad-positive MCF-7 breast cancer cells, but not in E-cad-negative MDA-MB-231
      cells. However, when the IGF-IR and E-cad were co-expressed in MDA-MB-231 cells,
      cell-cell adhesion was substantially increased. The IGF-IR-dependent cell-cell
      adhesion of MCF-7 cells was not related to altered expression of E-cad or alpha-,
      beta-, or gamma-catenins but coincided with the up-regulation of another element
      of the E-cad complex, zonula occludens-1 (ZO-1). ZO-1 expression (mRNA and
      protein) was induced by IGF-I and was blocked in MCF-7 cells with a tyrosine
      kinase-defective IGF-IR mutant. By co-immunoprecipitation, we found that ZO-1
      associates with the E-cad complex and the IGF-IR. High levels of ZO-1 coincided
      with an increased IGF-IR/alpha-catenin/ZO-1-binding and improved ZO-1/actin
      association, whereas down-regulation of ZO-1 by the expression of an anti-ZO-1
      RNA inhibited IGF-IR-dependent cell-cell adhesion. The results suggested that one
      of the mechanisms by which the activated IGF-IR regulates E-cad-mediated cell
      cell adhesion is overexpression of ZO-1 and the resulting stronger connections
      between the E-cad complex and the actin cytoskeleton. We hypothesize that in E
      cad-positive cells, the IGF-IR may produce antimetastatic effects.

PMID- 11518718
TI  - Murine notch homologs (N1-4) undergo presenilin-dependent proteolysis.
AB  - Oncogenic forms of Notch1, Notch2, and Notch4 appear to mimic signaling
      intermediates of Notch1 and suggest that the role of proteolysis in Notch
      signaling has been conserved. Here we demonstrate that extracellularly truncated
      Notch homologs are substrates for a presenilin-dependent gamma-secretase
      activity. Despite minimal conservation within the transmembrane domain, the
      requirement for a specific amino acid (P1' valine) and its position at the
      cleavage site relative to the cytosolic border of the transmembrane domain are
      preserved. Cleaved, untethered Notch intracellular domains from each receptor
      translocate to the nucleus and interact with the transcriptional regulatory
      protein CSL. All four Notch proteins display presenilin-dependent transactivating
      potential on a minimal promoter reporter. Thus, this study increases the number
      of biochemically characterized gamma-secretase substrates from two to five.
      Despite a high degree of structural homology and the presenilin-dependent
      activity of truncated Notch proteins, the extent that this reflects functional
      redundancy is unknown.

PMID- 11518719
TI  - Identification of a new class of molecules, the arachidonyl amino acids, and
      characterization of one member that inhibits pain.
AB  - In mammals, specific lipids and amino acids serve as crucial signaling molecules.
      In bacteria, conjugates of lipids and amino acids (referred to as lipoamino
      acids) have been identified and found to possess biological activity. Here, we
      report that mammals also produce lipoamino acids, specifically the arachidonyl
      amino acids. We show that the conjugate of arachidonic acid and glycine (N
      arachidonylglycine (NAGly)) is present in bovine and rat brain as well as other
      tissues and that it suppresses tonic inflammatory pain. The biosynthesis of NAGly
      and its degradation by the enzyme fatty acid amide hydrolase can be observed in
      rat brain tissue. In addition to NAGly, bovine brain produces at least two other
      arachidonyl amino acids: N-arachidonyl gamma-aminobutyric acid (NAGABA) and N
      arachidonylalanine. Like NAGly, NAGABA inhibits pain. These findings open the
      door to the identification of other members of this new class of biomolecules,
      which may be integral to pain regulation and a variety of functions in mammals.

PMID- 11518720
TI  - Glypicans: proteoglycans with a surprise.

PMID- 11518721
TI  - Herpesviruses and heparan sulfate: an intimate relationship in aid of viral
      entry.

PMID- 11518722
TI  - The link between heparan sulfate and hereditary bone disease: finding a function
      for the EXT family of putative tumor suppressor proteins.

PMID- 11518723
TI  - Encephalitogenic lymphoblast recruitment to resting CNS microvasculature: a
      natural immunosurveillance mechanism?

PMID- 11518724
TI  - Ferroportin mutation in autosomal dominant hemochromatosis: loss of function,
      gain in understanding.

PMID- 11518725
TI  - TGF-beta/Smad signaling defects in inflammatory bowel disease: mechanisms and
      possible novel therapies for chronic inflammation.

PMID- 11518726
TI  - A role for mitogen-activated protein kinase activation by integrins in the
      pathogenesis of psoriasis.
AB  - In normal epidermis, beta1 integrin expression is confined to the basal layer,
      whereas in hyperproliferative epidermis, integrins are also expressed in the
      suprabasal layers. Transgenic mice in which integrins are expressed suprabasally
      via the involucrin promoter have a sporadic psoriatic phenotype; however, the
      mechanism by which integrins contribute to the pathogenesis of psoriasis is
      unknown. We observed activation of mitogen-activated protein kinase (MAPK) in
      basal and suprabasal keratinocytes of human and transgenic mouse psoriatic
      lesions and healing mouse skin wounds, correlating in each case with suprabasal
      integrin expression. Phenotypically normal human and transgenic mouse epidermis
      did not contain activated MAPK. Transgene-positive keratinocytes produced more IL
      1alpha than controls did, and keratinocyte MAPK could be activated by ligation of
      suprabasal integrins or treatment with IL-1alpha. Constitutive activation of MAPK
      increased the growth rate of human keratinocytes and delayed the onset of
      terminal differentiation, recreating many of the histological features of
      psoriatic epidermis. We propose that activation of MAPK by integrins, either
      directly or through increased IL-1alpha production, is responsible for epidermal
      hyperproliferation in psoriasis and wound healing, and that the sporadic
      phenotype of the transgenic mice may reflect the complex mechanisms by which IL-1
      release and responsiveness are controlled in skin.

PMID- 11518727
TI  - Endothelium-specific loss of murine thrombomodulin disrupts the protein C
      anticoagulant pathway and causes juvenile-onset thrombosis.
AB  - The thrombomodulin (TM) gene was ablated in mice in a cell type-restricted manner
      from vascular endothelium by Cre-recombinase-mediated excision controlled by the
      endothelial cell lineage-specific Tie2 promoter. Forty percent of mutant (TMLox-)
      mice display a distinct lethal embryonic phenotype not observed in completely TM
      deficient embryos. The remaining 60% of TMLox mice survive beyond birth, but
      invariably succumb to a severe hypercoagulable state and massive thrombosis after
      3 weeks, terminating in a lethal consumptive coagulopathy. The progression of
      thrombosis was age- and sex-dependent. Disruption of the TM/protein C pathway was
      not associated with a latent proinflammatory state. Disease onset and progression
      could be prevented by warfarin anticoagulation. These results show that in mice,
      loss of endothelial cell TM function causes spontaneous and fatal thrombosis in
      the arterial and venous circulation, resulting from unfettered activation of the
      coagulation system. The combination of complete disease penetrance, uniform
      disease onset at young age, large vessel thrombosis of the extremities and
      multiple organ systems, and consumptive coagulopathy as the disease end-point
      provides a unique mouse model of human thrombotic disease.

PMID- 11518728
TI  - Critical role for the chemokine MCP-1/CCR2 in the pathogenesis of bronchiolitis
      obliterans syndrome.
AB  - Bronchiolitis obliterans syndrome (BOS) is the major limitation to survival after
      lung transplantation. Acute rejection, its main risk factor, is characterized by
      perivascular/bronchiolar leukocyte infiltration. BOS is characterized by
      persistent peribronchiolar leukocyte recruitment leading to airway fibrosis and
      obliteration. The specific mechanism(s) by which these leukocytes are recruited
      are unknown. Because MCP-1, acting through its receptor CCR2, is a potent
      mononuclear cell chemoattractant, we hypothesized that expression of this
      chemokine during an allogeneic-response promotes persistent recruitment of
      leukocytes and, ultimately, rejection. We found that elevated levels of
      biologically active MCP-1 in human bronchial lavage fluid (BALF) were associated
      with the continuum from acute to chronic allograft rejection. Translational
      studies in a murine model of BOS demonstrated increased MCP-1 expression
      paralleling mononuclear cell recruitment and CCR2 expression. Loss of MCP-1/CCR2
      signaling, as seen in CCR2(-/-) mice or in WT mice treated with neutralizing
      antibodies to MCP-1, significantly reduced recruitment of mononuclear phagocytes
      following tracheal transplantation and led to attenuation of BOS. Lymphocyte
      infiltration was not reduced under these conditions. We suggest that MCP-1/CCR2
      signaling plays an important role in recruitment of mononuclear phagocytes, a
      pivotal event in the pathogenesis of BOS.

PMID- 11518729
TI  - Alpha4-integrin-VCAM-1 binding mediates G protein-independent capture of
      encephalitogenic T cell blasts to CNS white matter microvessels.
AB  - Direct in vivo evidence is still lacking for alpha4-integrin-mediated T cell
      interaction with VCAM-1 on blood-brain barrier-endothelium in experimental
      autoimmune encephalomyelitis (EAE). To investigate a possible alpha4-integrin
      mediated interaction of encephalitogenic T cell blasts with VCAM-1 on the blood
      brain barrier white matter endothelium in vivo, we have developed a novel spinal
      cord window preparation that enabled us to directly visualize CNS white matter
      microcirculation by intravital fluorescence videomicroscopy. Our study provides
      the first in vivo evidence that encephalitogenic T cell blasts interact with the
      spinal cord white matter microvasculature without rolling and that alpha4
      integrin mediates the G protein-independent capture and subsequently the G
      protein-dependent adhesion strengthening of T cell blasts to microvascular VCAM
      1.

PMID- 11518730
TI  - Ron-mediated cytoplasmic signaling is dispensable for viability but is required
      to limit inflammatory responses.
AB  - Ron receptor activation induces numerous cellular responses in vitro, including
      proliferation, dissociation, and migration. Ron is thought to be involved in
      blood cell development in vivo, as well as in many aspects of the immune response
      including macrophage activation, antigen presentation, and nitric oxide
      regulation. In previous studies to determine the function of Ron in vivo, mice
      were generated with a targeted deletion of the extracellular and transmembrane
      regions of this gene. Mice homologous for this deletion appear to die early
      during embryonic development. To ascertain the in vivo function of Ron in more
      detail, we have generated mice with a germline ablation of the tyrosine kinase
      domain. Strikingly, our studies indicate that this domain of Ron, and therefore
      Ron cytoplasmic signaling, is not essential for embryonic development. While mice
      deficient in this domain are overtly normal, mice lacking Ron signaling have an
      altered ability to regulate nitric oxide levels and, in addition, have enhanced
      tissue damage following acute and cell-mediated inflammatory responses.

PMID- 11518731
TI  - Generation of experimental allergic airways inflammation in the absence of
      draining lymph nodes.
AB  - The objective of this study was to investigate the contribution of secondary
      lymphoid organs in the generation and maintenance of experimental allergic airway
      inflammation. We employed a previously reported murine model of respiratory
      mucosal allergic sensitization, induced by repeated aerosolizations of ovalbumin
      in the context of a GM-CSF airway environment. We executed this protocol in wild
      type (WT) and lymphotoxin-alpha-deficient mice (LTalpha-KO) mice, which are
      devoid of lymph nodes (LNs) and possess rudimentary spleen structures. Despite
      the lack of pulmonary LNs draining the airway compartment, LTalpha-KO mice were
      fully capable of mounting a robust inflammatory response in the airways,
      consisting of Th2 polarized CD4+ T cells and eosinophils. This was accompanied by
      IL-5, IL-13, and IFN-gamma production by splenocytes and generation of ovalbumin
      specific serum IgE. Exposure to the same antigen 7 weeks after complete
      resolution of airway inflammation once again induced a Th2 polarized infiltrate,
      demonstrating intact immunological memory. To investigate inherent plasticity in
      establishing antigen-specific immunity, mice were splenectomized before
      sensitization. Allergic sensitization was completely abrogated in splenectomized
      LTalpha-KO mice, compared with eusplenic LTalpha-KO controls. These data
      demonstrate that secondary lymphoid organs, either LN or spleen, are essential
      for the generation of allergic airway responses.

PMID- 11518732
TI  - Inhibition of cyclooxygenase-2 aggravates doxorubicin-mediated cardiac injury in
      vivo.
AB  - The clinical use of doxorubicin, an anthracycline chemotherapeutic agent, is
      limited by cardiotoxicity, particularly when combined with herceptin, an antibody
      that blocks the HER2 receptor. Doxorubicin induces cyclooxygenase-2 (COX-2)
      activity in rat neonatal cardiomyocytes. This expression of COX-2 limits
      doxorubicin-induced cardiac cell injury, raising the possibility that the
      administration of a prostaglandin may protect the heart during the in vivo
      administration of doxorubicin. Doxorubicin (15 mg/kg) administered to adult male
      Sprague Dawley rats induced COX-2 expression and activity in cardiac tissue.
      Prostacyclin generation measured as the excretion of 2,3-dinor-6-keto-PGF(1alpha)
      also increased, and this was blocked by a COX-2 inhibitor, SC236. In contrast,
      administration of a COX-1 inhibitor SC560 at a dose that reduced serum
      thromboxane B2 by more than 80% did not prevent the doxorubicin-induced increase
      in prostacyclin generation. Doxorubicin increased cardiac injury, detected as a
      rise in plasma cardiac troponin T, serum lactate dehydrogenase, and cardiomyocyte
      apoptosis; this was aggravated by coadministration of SC236 but not SC560. The
      degree of injury in animals treated with a combination of doxorubicin and SC236
      was attenuated by prior administration of the prostacyclin analogue iloprost.
      These data raise the possibility of protecting the heart during the
      administration of doxorubicin by prior administration of prostacyclin.

PMID- 11518733
TI  - Posttraumatic therapeutic vaccination with modified myelin self-antigen prevents
      complete paralysis while avoiding autoimmune disease.
AB  - Spinal cord injury results in a massive loss of neurons, and thus of function. We
      recently reported that passive transfer of autoimmune T cells directed against
      myelin-associated antigens provides acutely damaged spinal cords with effective
      neuroprotection. The therapeutic time window for the passive transfer of T cells
      was found to be at least 1 week. Here we show that posttraumatic T cell-based
      active vaccination is also neuroprotective. Immunization with myelin-associated
      antigens such as myelin basic protein (MBP) significantly promoted recovery after
      spinal cord contusion injury in the rat model. To reduce the risk of autoimmune
      disease while retaining the benefit of the immunization, we vaccinated the rats
      immediately after severe incomplete spinal cord injury with MBP-derived altered
      peptide ligands. Immunization with these peptides resulted in significant
      protection from neuronal loss and thus in a reduced extent of paralysis, assessed
      by an open-field behavioral test. Retrograde labeling of the rubrospinal tracts
      and magnetic resonance imaging supported the behavioral results. Further
      optimization of nonpathogenic myelin-derived peptides can be expected to lead the
      way to the development of an effective therapeutic vaccination protocol as a
      strategy for the prevention of total paralysis after incomplete spinal cord
      injury.

PMID- 11518734
TI  - Blocking Smad7 restores TGF-beta1 signaling in chronic inflammatory bowel
      disease.
AB  - TGF-beta1 functions as a negative regulator of T cell immune responses, signaling
      to target cells using the Smad family of proteins. We show here that Smad7, an
      inhibitor of TGF-beta1 signaling, is overexpressed in inflammatory bowel disease
      (IBD) mucosa and purified mucosal T cells. Both whole tissue and isolated cells
      exhibit defective signaling through this pathway, as measured by phospho-Smad3
      immunoreactivity. Specific antisense oligonucleotides for Smad7 reduce Smad7
      protein expression in cells isolated from patients with IBD, permitting the cells
      to respond to exogenous TGF-beta1. TGF-beta1 cannot inhibit proinflammatory
      cytokine production in isolated lamina propria mononuclear cells from patients
      with Crohn disease (CD), but inhibition of Smad7 restores TGF-beta1 signaling and
      enables TGF-beta1 to inhibit cytokine production. In inflamed mucosal tissue
      explants from patients with CD, inhibition of Smad7 also restores p-Smad3 and
      decreases proinflammatory cytokine production, an effect that is partially
      blocked by anti-TGF-beta1. These results show that Smad7 blockade of TGF-beta1
      signaling helps maintain the chronic production of proinflammatory cytokines that
      drives the inflammatory process in IBD and that inhibition of Smad7 enables
      endogenous TGF-beta to downregulate this response.

PMID- 11518735
TI  - A complex role for the progesterone receptor in the response to vascular injury.
AB  - Clinical studies of hormone replacement therapy to prevent cardiovascular
      diseases have heightened interest in the cardiovascular effects of progestins.
      However, the role of the progesterone receptor (PR) in vascular biology has not
      been studied in vivo. We studied ovariectomized female PR knockout (PRKO) mice
      and their wild-type (WT) littermates using the mouse carotid artery injury model.
      Placebo-treated PRKO mice showed significantly greater vascular medial
      hypertrophy and vascular smooth muscle cell (VSMC) proliferation in response to
      vascular injury than did WT mice. Progesterone had no significant effect in the
      PRKO mice, but worsened the response to injury in WT mice. VSMCs cultured from
      PRKO mouse aortae were markedly hyperproliferative, and their growth was not
      affected by progesterone. In contrast to the in vivo findings, progesterone
      inhibited proliferation of WT-derived VSMCs. Furthermore, reintroduction of PR
      into PRKO-derived VSMCs using adenoviral methods restored progesterone-mediated
      inhibition of proliferation to these cells. This effect was reversed by the PR
      antagonist, RU 486. Thus, the effects of PR and progesterone differ markedly
      between cultured VSMCs and intact blood vessels. These data demonstrate a direct
      role for the PR in regulating the response to vascular injury and VSMC
      proliferation.

PMID- 11518736
TI  - Autosomal-dominant hemochromatosis is associated with a mutation in the
      ferroportin (SLC11A3) gene.
AB  - Hemochromatosis is a progressive iron overload disorder that is prevalent among
      individuals of European descent. It is usually inherited in an autosomal
      recessive pattern and associated with missense mutations in HFE, an atypical
      major histocompatibility class I gene. Recently, we described a large family with
      autosomal-dominant hemochromatosis not linked to HFE and distinguished by early
      iron accumulation in reticuloendothelial cells. Through analysis of a large
      pedigree, we have determined that this disease maps to 2q32. The gene encoding
      ferroportin (SLC11A3), a transmembrane iron export protein, lies within a
      candidate interval defined by highly significant lod scores. We show that the
      iron-loading phenotype in autosomal-dominant hemochromatosis is associated with a
      nonconservative missense mutation in the ferroportin gene. This missense
      mutation, converting alanine to aspartic acid at residue 77 (A77D), was not seen
      in samples from 100 unaffected control individuals. We propose that partial loss
      of ferroportin function leads to an imbalance in iron distribution and a
      consequent increase in tissue iron accumulation.

PMID- 11518739
TI  - Acute hyperglycemia induces an oxidative stress in healthy subjects.

PMID- 11518737
TI  - Peripheral melatonin mediates neural stimulation of duodenal mucosal bicarbonate
      secretion.
AB  - Melatonin is released from intestinal enterochromaffin cells and from the pineal
      gland, but its role in gastrointestinal function is largely unknown. Our aim was
      to study the involvement of intestinal and central nervous melatonin in the
      neurohumoral control of the duodenal mucosa-protective bicarbonate secretion.
      Working in anesthetized rats, we cannulated a 12-mm segment of duodenum with an
      intact blood supply and titrated the local bicarbonate secretion with pH-stat.
      Melatonin and receptor ligands were supplied to the duodenum by close intra
      arterial infusion. Even at low doses, melatonin and the full agonist 2-iodo-N
      butanoyl-5-methoxytryptamine increased duodenal bicarbonate secretion. Responses
      were inhibited by the predominantly MT2-selective antagonist luzindole but not by
      prazosin, acting at MT3 receptors. Also, luzindole almost abolished the marked
      rise in secretion induced by intracerebroventricular infusion of the adrenoceptor
      agonist phenylephrine. This response was also abolished by sublaryngeal ligation
      of all nerves around the carotid arteries. However, it was insensitive to truncal
      vagotomy alone or sympathectomy alone and was unaffected by removal of either the
      pineal gland or pituitary gland. Thus, melatonin stimulates duodenal bicarbonate
      secretion via action at enterocyte MT2-receptors and mediates neural stimulation
      of the secretion.

PMID- 11518740
TI  - Ablation of hepatocellular carcinoma.

PMID- 11518741
TI  - Recent advances in the chemotherapy of non-small cell lung cancer.
AB  - Chemotherapeutic regimens containing new anticancer agents in combination with
      cisplatin and carboplatin have been demonstrated to be equivalently active
      against advanced non-small cell lung cancer. The choice of a chemotherapeutic
      regimen depends on differences in time to progression, response rate, toxicity
      profile, cost and symptom relief. Several other strategies, such as three-drug
      combinations, sequential use of a third drug, weekly administration, etc., have
      been evaluated to improve the chemotherapeutic effect. The sequencing of the
      human genome may permit targeting of specific abnormalities related to each lung
      cancer with target-based drugs. This should increase the possibility of
      application of individualized therapy and, we would hope, improve survival.

PMID- 11518742
TI  - Expression of carcinoembryonic antigen in peripheral- or central-located small
      cell lung cancer: its clinical significance.
AB  - BACKGROUND: Small cell lung cancer (SCLC) has a higher percentage of hilar masses
      than other histological types of lung cancer. The primary site is usually
      adjacent to the hilum, but we often observe primary sites in the peripheral lung
      field. In this study, our objectives were to elucidate whether peripheral-located
      small cell lung cancer (PSCLC) is an independent entity and whether it differs
      clinically from central-located small cell lung cancer (CSCLC). METHODS: We
      reviewed the clinical and pathological features of 52 patients treated at Kagawa
      Medical University Hospital between 1987 and 1996 with a diagnosis of SCLC. We
      defined CSCLC as a tumor whose primary site is located in the segmental bronchi
      or more proximally and PSCLC as a tumor located distal to the subsegmental
      bronchi. Twenty-one PSCLC patients and 31 CSCLC patients were identified. Kaplan
      Meier survival curves were constructed and comparisons were made between PSCLC
      and CSCLC by the log-rank test. The carcinoembryonic antigen (CEA) level was also
      evaluated in each group. RESULTS: Although the percentage of limited disease (LD)
      in the patients with PSCLC was higher than that in the patients with CSCLC, the 3
      year survival rate of PSCLC tended to be worse than that of CSCLC (9% for
      patients with PSCLC and 29% for those with CSCLC). Survival curves of patients
      with PSCLC also tended to be worse than those of patients with CSCLC, not only in
      the limited disease group but also in the extensive disease (ED) group. In
      addition, the mean CEA value in patients with PSCLC was higher than that in
      patients with CSCLC (p < 0.001), whereas the neuron specific enolase (NSE) level
      was not significantly different between PSCLC and CSCLC. The median survival of
      patients with pretherapeutic CEA titers of > or =5 ng/ml was significantly
      shorter than that in patients with CEA levels <5 ng/ml. CONCLUSION: These
      findings suggest that the survival of SCLC patients with a high CEA level was
      significantly shorter than that of patients with a low CEA level. In addition,
      CEA levels in PSCLC patients were significantly higher than those in CSCLC
      patients. However, the survivals of LD or ED patients with PSCLC and CSCLC were
      not statistically different.

PMID- 11518743
TI  - Generation of autologous tumor-specific T cell clones from a patient with
      adenosquamous carcinoma of the lung.
AB  - BACKGROUND: Adenosquamous carcinoma of the lung is not a common cancer, but its
      prognosis is worse than that of adenocarcinoma or squamous cell carcinoma.
      Therefore, new therapeutic strategies need to be developed to treat this type of
      lung cancer. Recently, vaccination using tumor antigens which are recognized by
      cytotoxic T lymphocytes (CTL) has been applied mainly to melanoma patients. We
      therefore attempted to establish T cell clones specific for autologous tumor
      cells (AT) from a patient with adenosquamous carcinoma in order to analyze the
      specific immune responses against AT. METHODS: A lung adenosquamous carcinoma
      cell line was established from a resected tumor obtained from a 72-year-old
      patient. Regional lymph node lymphocytes were stimulated weekly with CD80
      transfected AT to induce CTL. The CTL activities were assessed by a standard
      (51)Cr release assay and by cytokine release. RESULTS: We succeeded in inducing
      an AT-specific CTL line. Using a limiting dilution method, eight T cell clones
      were established. AT-specific activity was observed in three CD8(+) T cell clones
      and one CD4(+) T cell clone out of the eight clones tested. Anti-HLA class I and
      anti-HLA-B/C mAbs inhibited IFN-gamma production from the AT-specific CD8(+)
      clones co-cultured with AT, thus indicating the restriction element to be HLA
      B*5201 or HLA-Cw*1202. In contrast, the CD4(+) T cell clone recognized AT in an
      HLA class II-restricted manner. CONCLUSIONS: These results are the first
      demonstration of a successful induction of AT-specific T cell clones from a
      patient with lung adenosquamous carcinoma. It may therefore supply a possible way
      to apply specific immunotherapy to this type of lung cancer.

PMID- 11518744
TI  - Management of the axilla in breast cancer: a comparative study between sentinel
      lymph node biopsy and four-node sampling procedure.
AB  - BACKGROUND: The aim of this study was to compare the efficacy of sentinel lymph
      node biopsy and that of four-node sampling for predicting other nodal status in
      breast cancer. METHODS: 206 patients with operable breast cancer were enrolled.
      The identification of sentinel lymph nodes (SLNs) was carried out in 110 patients
      using a gamma probe after injection of radioactive tin colloids. Four palpable
      lymph nodes (FNs) were removed from the lower axilla at the first step of
      axillary dissection in 98 patients. The predictive value of nodal status was
      compared between SLNs and FNs, based on the pathological findings of all
      dissected lymph nodes. To examine the relationship between SLNs and FNs, we chose
      the FNs retrospectively (defined as rFNs) from among all nodes in SLNs. RESULTS:
      SLNs were identified in 108 (98%) of 110 patients. With one patient having skip
      metastasis, the accuracy and sensitivity were 99 and 98%, respectively. In the
      four-node sampling (FNS) group, two in 98 patients had skip metastasis and the
      accuracy and sensitivity were 98 and 96%, respectively. Findings on the
      relationship between these methods of biopsy were as follows: (i) rFNs included
      SLNs in 79 patients (73%); (ii) rFNs partially included SLNs in 24 patients
      (22%); and (iii) no relationship was evident in five patients (5%). CONCLUSIONS:
      The accuracy/sensitivity of FNs was comparable to that of SLNs. FNS can be
      considered to represent a highly promising approach and may be used as an
      alternative procedure that can be performed safely and easily in any institute.

PMID- 11518745
TI  - Radiofrequency ablation and percutaneous ethanol injection in patients with small
      hepatocellular carcinoma: a comparative study.
AB  - BACKGROUND: Radiofrequency ablation (RFA) is a novel thermal ablation technique
      to achieve coagulative necrosis of hepatocellular carcinoma. A study was
      conducted to compare the antitumor effect and adverse effect of RFA with those of
      percutaneous ethanol injection (PEI) in patients with solitary small
      hepatocellular carcinoma. METHODS: The study population consisted of 119
      consecutive patients with solitary hepatocellular carcinoma smaller than 3 cm in
      diameter. Among these, 23 patients were treated with RFA and the remaining 96
      patients were treated with PEI. The antitumor effects of both treatments were
      assessed by contrast-enhanced computed tomography 1 month after treatment.
      RESULTS: Complete tumor necrosis was achieved in 23 patients (100%) of the RFA
      group and 90 patients (94%) of the PEI group (p = 0.48) and local recurrence
      rates at 1 year were 15% in the RFA group and 14% in the PEI group (p = 0.80).
      RFA required an average of 1.5 sessions to achieve complete necrosis, whereas PEI
      required an average of 4.0 sessions. As a consequence, the hospital stay in the
      RFA group (median 10 days) was significantly shorter than that in the PEI group
      (median 17 days). There were no serious adverse effects or complications except
      for one case of cholangitis in the PEI group, although deterioration of serum
      transaminase after RFA was significantly more severe than that after PEI.
      CONCLUSION: RFA achieved complete tumor necrosis for small hepatocellular
      carcinoma with fewer treatment sessions compared with PEI. There were no serious
      complications.

PMID- 11518746
TI  - Prognostic value of nm23 expression in stage IB1 cervical carcinoma.
AB  - BACKGROUND: The purpose of this retrospective study was to evaluate the patterns
      of nm23 expression in stage IB1 squamous cell carcinoma of the uterine cervix, to
      compare nm23 expression with clinicopathological findings and to assess its
      prognostic value. METHODS: Twenty-seven patients with stage IB1 squamous cell
      carcinoma of the uterine cervix underwent abdominal radical hysterectomy and
      pelvic lymph node dissection. Expression of nm23 was studied
      immunohistochemically, followed by amplification and direct sequencing of exons 4
      and 5 of the nm23 gene. RESULTS: Overexpression of nm23 was detected in 18.5% of
      the tumors and low expression was seen in 33.3%, while negative expression was
      found in 48.1% of the tumors. Deep cervical stromal invasion (> or =1/2) was
      found to be associated with the increased risk of lymph node metastases (odds
      ratio = 17.5). A significantly lower percentage of patients survived when nm23
      overexpression was observed (p = 0.0063). Univariate analysis revealed that tumor
      size (2-3.9 cm), lymph node metastasis, tumor invasion into parametria, tumor
      invasion into blood/lymph vessel, squamous cell carcinoma (> or =2 ng/ml) and
      nm23 overexpression had a significantly lower recurrence-free survival rate of
      the patients. None of the above factors was significant according to multivariate
      analysis. There were no mutations in exons 4 and 5 of the nm23 gene in stage IB1
      squamous cell carcinoma of the uterine cervix. CONCLUSIONS: This study suggests
      that expression of nm23 may be indicative of an unfavorable prognosis in patients
      with stage IB1 squamous cell carcinoma of the uterine cervix.

PMID- 11518747
TI  - Pulmonary intravascular lymphoma complicated with Pneumocystis carinii pneumonia:
      a case report.
AB  - We report a case of intravascular lymphoma (IVL) complicated with Pneumocystis
      carinii pneumonia (PCP). A 65-year-old male complaining of dyspnea and dementia
      was diagnosed to have pulmonary IVL by transbronchial lung biopsy. Concomitantly,
      deoxyribonucleic acid sequence specific to Pneumocystis carinii was detected in
      bronchoalveolar lavage fluid by polymerase chain reaction. Differential responses
      to the sequential treatments for PCP and IVL implied that increased serum lactate
      dehydrogenase (LDH) was due to PCP, whereas hypoxemia and dementia were due to
      IVL. Although pulmonary IVL and PCP share many clinical presentations, exact
      diagnosis is essential for their successful treatment.

PMID- 11518748
TI  - A case of lung metastasis from endometrial adenoacanthoma 17 years after initial
      treatment.
AB  - In March 1982, a 60-old woman presented with an International Federation of
      Gynecology and Obstetrics grade 1, stage Ib endometrial adenoacanthoma,
      histological subtype of endometrial carcinoma. The patient underwent radical
      hysterectomy and was followed up for 10 years, without disease. In August 1998,
      an abnormal shadow in the right lung was suggested on a chest X-ray film at her
      routine health check-up and she came to our hospital for further evaluation. A
      thin-section computed tomographic scan of the chest suggested a malignant lung
      tumor, but the diagnosis remained tentative. Open biopsy was recommended, but the
      patient refused and was followed up on an outpatient basis. In November 1999, a
      thin-section computed tomographic scan of the chest revealed a slightly enlarged
      tumor and laboratory examination showed a high serum progastrin-releasing peptide
      concentration of 90.7 pg/ml. We performed partial resection of right upper lobe
      with video-assisted thoracic surgery. Pathological examination confirmed the lung
      tumor had metastasized from endometrial adenoacanthoma. Immunohistochemical
      stainings of estrogen receptor and progesterone receptor were positive both in
      the primary and lung tumor, only in the component of adenocarcinoma. After
      surgery, the serum progastrin-releasing peptide concentration remained unchanged.
      The patient is currently alive and free of disease.

PMID- 11518749
TI  - Isolated splenic metastasis of sigmoid colon cancer: a case report.
AB  - We report the case of a 62-year-old man who developed isolated splenic metastasis
      of sigmoid colon cancer. The patient underwent left hemicolectomy for Dukes C
      sigmoid colon cancer in February 1997. In March 1999, an abdominal CT scan
      revealed a tumor 3 cm in size at the inferior pole of the spleen. The tumor was
      hyperechoic on ultrasonography. The serum carcinoembryonic antigen level was
      normal. Since no other site of recurrence was identified, a splenectomy was
      performed with a curative intent. At laparotomy, neither hepatic metastasis,
      peritoneal dissemination, lymph node metastasis nor local recurrence was
      detected. Histological findings of the splenic tumor were compatible with
      metastasis of the previously resected sigmoid colon adenocarcinoma. The patient
      has been disease-free for 19 postoperative months. Immunohistochemical staining
      for urokinase-type plasminogen activator was positive in primary sigmoid colon
      cancer and splenic metastasis, but negative in lymph node metastasis; results
      that possibly reflect the difference in progenitor cells between splenic
      metastasis and lymph node metastasis or the difference in the microenvironment of
      cancer cells between the spleen and lymph nodes. Based on the present case, we
      recommend that clinicians pay close attention to the spleen for the early
      diagnosis of isolated splenic metastasis when routinely evaluating abdominal CT
      scans and abdominal ultrasonography following curative resection of primary
      colorectal cancer.

PMID- 11518750
TI  - DNA variants of BAT-25 in Japanese, a locus frequently used for analysis of
      microsatellite instability.
AB  - BAT-25 is a DNA marker, intragenic to the c-kit protooncogene, assigned to 4q12,
      containing a polythymine tract, mostly repeats of 25 poly(T) (T25). The BAT-25
      locus is frequently used in the analysis of microsatellite instability (MSI) in
      cancer tissues. The number of poly(T) repeats at BAT-25 is reported to be quasi
      monomorphic and this property permits the easy identification of the MSI status.
      We report DNA variants of BAT-25, in one patient with hereditary nonpolyposis
      colorectal cancer presenting T21 and T25 alleles and another carrying T18 and T25
      alleles in the analysis of 100 normal Japanese donors. Observed allelic
      frequencies were 0.5% for both T21 and T18 alleles. So far, DNA variants of BAT
      25 locus have been reported in African Americans with relatively high
      frequencies, but not in Japanese.

PMID- 11518751
TI  - Germline p53 mutation in a patient with multiple primary cancers.
AB  - We report a case of multiple primary cancers having a germline missense mutation
      of the p53 gene. The patient was a Japanese female and had a history of five
      different types of cancers. PCR/direct sequencing analysis revealed the presence
      of a nucleotide substitution, AGC (Ser) to AGG (Arg), at codon 106 of the p53
      gene in DNA from non-cancerous breast tissue. This is the first case of germline
      p53 mutation at codon 106, and could contribute to establishing correlations
      between the types and locations of germline p53 mutations and their phenotypical
      consequences.

PMID- 11518753
TI  - Regulation and intracellular trafficking of the ABCA1 transporter.
AB  - The discovery of the role of the ATP-binding cassette transporter A1 (ABCA1) in
      mediating apolipoprotein A-I-mediated efflux has led to a dramatic increase in
      our knowledge of the molecular mechanisms involved in cholesterol efflux and
      cellular metabolism. In this review, we discuss several aspects of ABCA1
      regulation including i) transcriptional regulation, ii) substrate specificity and
      availability, iii) accessory proteins, iv) acceptor specificity and availability,
      and v) protein trafficking. The majority of studies of ABCA1 regulation to date
      have focused on the identification of promoter elements that determine ABCA1 gene
      transcription. Here we also review the potential functional role of ABCA1 in
      reverse cholesterol transport. Given the key role that ABCA1 plays in cholesterol
      homeostasis, it is likely that there are multiple mechanisms for controlling the
      overall transporter activity of ABCA1.

PMID- 11518754
TI  - Structure of apolipoprotein B-100 in low density lipoproteins.
AB  - There is general consensus that amphipathic alpha-helices and beta sheets
      represent the major lipid-associating motifs of apolipoprotein (apo)B-100. In
      this review, we examine the existing experimental and computational evidence for
      the pentapartite domain structure of apoB. In the pentapartite nomenclature
      presented in this review (NH(2)-betaalpha(1)-beta(1)-alpha(2)-beta(2)-alpha(3)
      COOH), the original alpha(1) globular domain (Segrest, J. P. et al. 1994.
      Arterioscler. Thromb. 14: 1674;-1685) is expanded to include residues 1;-1,000
      and renamed the betaalpha(1) domain. This change reflects the likelihood that the
      betaalpha(1) domain, like lamprey lipovitellin, is a globular composite of alpha
      helical and beta-sheet secondary structures that participates in lipid
      accumulation in the co-translationally assembled prenascent triglyceride-rich
      lipoprotein particles. Evidence is presented that the hydrophobic faces of the
      amphipathic beta sheets of the beta(1) and beta(2) domains of apoB-100 are in
      direct contact with the neutral lipid core of apoB-containing lipoproteins and
      play a role in core lipid organization. Evidence is also presented that these
      beta sheets largely determine LDL particle diameter. Analysis of published data
      shows that with a reduction in particle size, there is an increase in the number
      of amphipathic helices of the alpha(2) and alpha(3) domains associated with the
      surface lipids of the LDL particle; these increases modulate the surface pressure
      decreases caused by a reduction in radius of curvature. The properties of the LDL
      receptor-binding region within the overall domain structure of apoB-100 are also
      discussed. Finally, recent three-dimensional models of LDL obtained by
      cryoelectron microscopy and X-ray crystallography are discussed. These models
      show three common features: a semidiscoidal shape, a surface knob with the
      dimensions of the betaC globular domain of lipovitellin, and planar multilayers
      in the lipid core that are approximately 35 A apart; the multilayers are thought
      to represent cholesteryl ester in the smectic phase. These models present a
      conundrum: are LDL particles circulating at 37 degrees C spheroidal in shape, as
      generally assumed, or are they semidiscoidal in shape, as suggested by the
      models? The limited evidence available supports a spheroidal shape.

PMID- 11518755
TI  - Docosahexaenoic acid synthesis from n-3 polyunsaturated fatty acids in
      differentiated rat brain astrocytes.
AB  - DHA, the main n-3 PUFA in the brain, is synthesized from n-3 PUFA precursors by
      astrocytes. To assess the potential of this process to supply DHA for the brain,
      we investigated whether the synthesis in astrocytes is dependent on DHA
      availability. Rat brain astrocytes differentiated with dibutyryl cAMP and
      incubated in media containing 10% fetal bovine serum synthesized DHA from alpha
      linolenic acid ([1-(14)C]18:3n-3), docosapentaenoic acid ([3-(14)C]22:5n-3),
      tetracosapentaenoic acid ([3-(14)C]24:5n-3), and tetracosahexaenoic acid ([3
      (14)C]24:6n-3). When DHA was added to media containing a 5 microM concentration
      of these (14)C-labeled n-3 PUFA, radiolabeled DHA synthesis was reduced but not
      completely suppressed even when the DHA concentration was increased to 15 microM.
      Radiolabeled DHA synthesis also was reduced but not completely suppressed when
      the astrocytes were treated with 30 microM DHA for 24 h before incubation with 5
      microM [1-(14)C]18:3n-3.These findings indicate that although the DHA synthesis
      in astrocytes is dependent on DHA availability, some synthesis continues even
      when the cells have access to substantial amounts of DHA. This suggests that DHA
      synthesis from n-3 PUFA precursors is a constitutive process in the brain and,
      therefore, is likely to have an essential function.

PMID- 11518756
TI  - Localization of bilirubin in phospholipid bilayers by parallax analysis of
      fluorescence quenching.
AB  - It has been proposed that the neurotoxicity observed in severely jaundiced
      infants results from the binding of unconjugated bilirubin to nerve cell
      membranes. However, despite potentially important clinical ramifications, there
      remains significant controversy regarding the physical nature of bilirubin
      membrane interactions. We used the technique of parallax analysis of fluorescence
      quenching (Chattopadhyay, A., and E. London. 1987. Biochemistry. 26: 39;-45) to
      measure the depth of penetration of bilirubin in model phospholipid bilayers. The
      localization of unconjugated bilirubin and ditaurobilirubin within small
      unilamellar vesicles composed of dioleoylphosphatidylcholine was determined
      through an analysis of the quenching of bilirubin fluorescence by spin-labeled
      phospholipids, and by bilirubin-mediated quenching of a series of anthroyloxy
      fatty acid probes at various depths within the membrane bilayer. Findings were
      further verified with potassium iodide as an aqueous quencher. Our results
      indicate that, at pH 10, unconjugated bilirubin localizes approximately 20 A from
      the bilayer center, in the region of the polar head groups. Further analyses
      suggest a modest influence of pH, membrane cholesterol content, and vesicle
      diameter on the bilirubin penetration depth. Taken together, these data support
      that, under physiologic conditions, bilirubin localizes to the polar region of
      phospholipid bilayers, near the membrane-water interface.

PMID- 11518757
TI  - Decreased hepatic accumulation and enhanced esterification of cholesterol in mice
      deficient in mdr1a and mdr1b P-glycoproteins.
AB  - Class I P-glycoproteins [Pgp; MDR1 (ABCB1) in humans, mdr1a and mdr1b in mice]
      confer resistance to structurally diverse chemotherapeutic drugs in cultured
      cells and intact animals, but the function of these proteins in normal physiology
      remains poorly characterized. Based on studies in cell culture, a putative role
      for class I Pgp in absorption and intracellular trafficking of sterols has been
      proposed. We examined wild-type and mdr1a(-/)-/1b(-/)- mice to determine whether
      class I Pgp affects cholesterol absorption and esterification in vivo. Using a
      dual-isotope protocol, absorption of orally administered radiolabeled cholesterol
      into serum did not differ between wild-type and mdr1a(-/)-/1b(-/)- mice,
      demonstrating that class I Pgp is not essential for overall absorption of
      cholesterol through the intestine. However, the ratio of oral to intravenous
      labeled cholesterol in liver was decreased significantly in mdr1a(-/)-/1b(-/)-
      mice. In the liver, but not other tested organs, deletion of class I Pgp enhanced
      kinetics of esterification of an oral bolus of radiolabeled cholesterol without
      affecting esterification of cholesterol administered intravenously. Steady-state
      hepatic content of cholesterol and esterified cholesterol also were unaffected by
      absence of mdr1a and mdr1b.Thus, in normal animals, class I Pgp functions to
      kinetically increase hepatic accumulation and decrease esterification of orally
      administered cholesterol in vivo.

PMID- 11518758
TI  - Impaired synthesis of DHA in patients with X-linked retinitis pigmentosa.
AB  - Many patients with X-linked retinitis pigmentosa (XLRP) have lower than normal
      blood levels of the long-chain polyunsaturated omega3 fatty acid docosahexaenoic
      acid (DHA; 22:6omega3). This clinical trial was designed to test whether down
      regulation of DHA biosynthesis might be responsible for these reduced DHA levels.
      DHA biosynthesis was assessed in five severely affected patients with XLRP and in
      five age-matched controls by quantifying conversion of [U-(13)C]alpha-linolenic
      acid (alpha-LNA) to [(13)C]DHA. Following oral administration of [U-(13)C]alpha
      LNA, blood samples were collected at designated intervals for 21 days and
      isotopic enrichment of all omega3 fatty acids was determined by gas
      chromatography/mass spectroscopy. Activity of each metabolic step in the
      conversion of alpha-LNA to DHA was determined by comparison of the ratios of the
      integrated concentration of (13)C-product to (13)C-precursor in plasma total
      lipid fractions. The ratio of [(13)C]DHA to [(13)C]18:3omega3 (the entire
      pathway) and that of [(13)C]20:5omega3 to [(13)C]20:4omega3 (Delta(5)-desaturase)
      were significantly lower in patients versus controls (P = 0.03 and 0.05,
      respectively). The estimated biosynthetic rates of [(13)C]20:5omega3,
      [(13)C]22:5omega3, [(13)C]24:5omega3, [(13)C]24:6omega3, and [(13)C]22:6omega3
      were significantly lower in XLRP patients (42%, 43%, 31%, 18%, and 32% of control
      values, respectively; P < 0.04), supporting down-regulation of Delta(5)
      desaturase in XLRP. The disappearance of (13)C-labeled fatty acids from plasma
      was not greater in XLRP patients compared with controls, suggesting that XLRP was
      not associated with increased rates of fatty acid oxidation or other routes of
      catabolism.Thus, despite individual variation among both patients and controls,
      the data are consistent with a lower rate of Delta(5)-desaturation, suggesting
      that decreased biosynthesis of DHA may contribute to lower blood levels of DHA in
      patients with XLRP.

PMID- 11518759
TI  - Nuclear receptor-mediated repression of human cholesterol 7alpha-hydroxylase gene
      transcription by bile acids.
AB  - Hydrophobic bile acids strongly repressed transcription of the human cholesterol
      7alpha-hydroxylase gene (CYP7A1) in the bile acid biosynthetic pathway in the
      liver. Farnesoid X receptor (FXR) repressed CYP7A1/Luc reporter activity in a
      transfection assay in human liver-derived HepG2 cells, but not in human embryonic
      kidney (HEK) 293 cells. FXR-binding activity was required for bile acid
      repression of CYP7A1 transcription despite the fact that FXR did not bind to the
      CYP7A1 promoter. FXR-induced liver-specific factors must be required for
      mediating bile acid repression. Bile acids and FXR repressed endogenous CYP7A1
      but stimulated alpha-fetoprotein transcription factor (FTF) and small heterodimer
      partner (SHP) mRNA expression in HepG2 cells. Feeding of rats with
      chenodeoxycholic acid repressed CYP7A1, induced FTF, but had no effect on SHP
      mRNA expression in the liver. FTF strongly repressed CYP7A1 transcription in a
      dose-dependent manner, and SHP further inhibited CYP7A1 in HepG2 cells, but not
      in HEK 293 cells. FXR only moderately stimulated SHP transcription, whereas FTF
      strongly inhibited SHP transcription in HepG2 cells. Results revealed that FTF
      was a dominant negative factor that was induced by bile acid-activated FXR to
      inhibit both CYP7A1 and SHP transcription. Differential regulation of FTF and SHP
      expression by bile acids may explain the wide variation in CYP7A1 expression and
      the rate of bile acid synthesis and regulation in different species.

PMID- 11518760
TI  - Dynamic and stable pools of apoE differ functionally at the HepG2 cell surface.
AB  - Synthesis of apolipoprotein (apo)E in hepatocytes leads to both secretion and
      retention in cell surface pools. Inclusion of Brefeldin A to HepG2 cells prompted
      a rapid decrease of cell surface apoE to about 37% of control values after a 3-h
      incubation. The t(1/2) for this dynamic pool was estimated to be 15 min. In
      contrast, a stable fraction of apoE (t(1/2) > 20 h) was found in association with
      the extracellular matrix (ECM). Increased content of apoE on the ECM correlated
      with decreased binding of VLDL. Decreased apoE on the cell surface correlated
      with increased binding of VLDL to cells. Collectively, this suggests that
      glycosaminoglycan-bound apoE can occlude binding sites for apoE-containing
      lipoproteins on glycosaminoglycans. In solid-phase assays, heparin, suramin, and
      chondroitin sulfates A and B efficiently inhibited the binding of apoE to heparan
      sulfate proteoglycans, but were unable to displace apoE from this
      glycosaminoglycan. Finally, decreasing cell surface apoE with suramin
      subsequently decreased the apoE content on secreted apoB-containing lipoproteins
      without affecting the overall secretion of apoE or apoB to the extracellular
      medium. In summary, cell surface apoE comprises both dynamic fractions, which can
      be donated to newly secreted lipoproteins, and stable fractions, which may act to
      minimize the unproductive binding of lipoproteins to the ECM.

PMID- 11518761
TI  - Dipalmitoylphosphatidylcholine and cholesterol in monolayers spread from adsorbed
      films of pulmonary surfactant.
AB  - Pulmonary surfactant forms a surface film that consists of a monolayer and a
      monolayer-associated reservoir. The extent to which surfactant components
      including the main component, dipalmitoylphosphatidylcholine (DPPC), are adsorbed
      into the monolayer, and how surfactant protein SP-A affects their adsorptions, is
      not clear. Transport of cholesterol to the surface region from dispersions of
      bovine lipid extract surfactant [BLES(chol)] with or without SP-A at 37 degrees C
      was studied by measuring surface radioactivities of [4-(14)C]cholesterol-labeled
      BLES(chol), and the Wilhelmy plate technique was used to monitor adsorption of
      monolayers. Results showed that transport of cholesterol was lipid concentration
      dependent. SP-A accelerated lipid adsorption but suppressed the final level of
      cholesterol in the surface. Surfactant adsorbed from a dispersion with or without
      SP-A was transferred via a wet filter paper to a clean surface, where the surface
      radioactivity and surface tension were recorded simultaneously. It was observed
      that 1) surface radioactivity was constant over a range of dispersion
      concentrations; 2) cholesterol and DPPC were transferred simultaneously; and 3)
      SP-A limited transfer of cholesterol. These results indicate that non-DPPC
      components of pulmonary surfactant can be adsorbed into the monolayer. Studies in
      the transfer of [1-(14)C]DPPC-labeled BLES(chol) to an equal or larger clean
      surface area revealed that SP-A did not increase selective adsorption of DPPC
      into the monolayer. Evaluation of transferred surfactant with a surface balance
      indicated that it equilibrated as a monolayer. Furthermore, examination of
      transferred surfactants from dispersions with and without prespread BLES(chol)
      monolayers revealed a functional contiguous association between adsorbed
      monolayers and reservoirs.

PMID- 11518762
TI  - Lysophosphatidylcholine and lyso-PAF display PAF-like activity derived from
      contaminating phospholipids.
AB  - Lysophosphatidylcholine is an abundant component of plasma and oxidized LDL that
      displays several biological activities, some of which may occur through the
      platelet-activating factor (PAF) receptor. We find that commercial
      lysophosphatidylcholine, its alkyl homolog (lyso-PAF), and PAF all induce
      inflammation in a murine model of pleurisy. Hydrolysis of PAF to lyso-PAF by
      recombinant PAF acetylhydrolase abolished this eosinophilic infiltration,
      implying that lyso-PAF should not have displayed inflammatory activity.
      Saponification of lyso-PAF or PAF acetylhydrolase treatment of lyso-PAF or
      lysophosphatidylcholine abolished activity; neither lysolipid should contain
      susceptible sn-2 residues, suggesting contaminants account for the bioactivity.
      Lyso-PAF and to a lesser extent lysophosphatidylcholine stimulated Ca(2+)
      accumulation in 293 cells stably transfected with the human PAF receptor, and
      this was inhibited by specific PAF receptor antagonists. Again, treatment of lyso
      PAF or lysophosphatidylcholine with recombinant PAF acetylhydrolase, a
      nonselective phospholipase A(2), or saponification of lyso-PAF destroyed the PAF
      like activity, a result incompatible with lyso-PAF or lysophosphatidylcholine
      being the actual agonist. We conclude that neither lyso-PAF nor
      lysophosphatidylcholine is a PAF receptor agonist, nor are they inflammatory by
      themselves. We suggest that PAF or a PAF-like mimetic accounts for inflammatory
      effects of lysophosphatidylcholine and lyso-PAF.

PMID- 11518763
TI  - Cholecystectomy prevents expansion of the bile acid pool and inhibition of
      cholesterol 7alpha-hydroxylase in rabbits fed cholesterol.
AB  - To study the effect of cholecystectomy on the regulation of classic and
      alternative bile acid syntheses, gallbladder-intact (n = 20) and
      cholecystectomized (n = 20) New Zealand White rabbits were fed either chow or
      chow with 2% cholesterol (3 g/day). After 10 days, bile fistulas were constructed
      in half of each rabbit group to recover and measure the bile acid pool and
      biliary bile acid flux. After cholesterol feeding, the bile acid pool size
      increased from 268 +/- 55 to 444 +/- 77 mg (P < 0.01) with a 2-fold rise in the
      biliary bile acid flux in intact rabbits but did not expand the bile acid pool
      (270 +/- 77 vs. 276 +/- 62 mg), nor did the biliary bile acid flux increase in
      cholecystectomized rabbits. Ileal apical sodium-dependent bile acid transporter
      protein increased 46% from 93 +/- 6 to 136 +/- 23 units/mg (P < 0.01) in the
      intact rabbits but did not change in cholecystectomized rabbits (104 +/- 14 vs.
      99 +/- 19 units/mg) after cholesterol feeding. Cholesterol 7alpha-hydroxylase
      activity was inhibited 59% (P < 0.001) while cholesterol 27-hydroxylase activity
      rose 83% (P < 0.05) after cholesterol feeding in the intact rabbits but neither
      enzyme activity changed significantly in cholesterol-fed cholecystectomized
      rabbits. Fecal bile acid outputs reflecting bile acid synthesis increased
      significantly in the intact but not in the cholecystectomized rabbits fed
      cholesterol. Removal of the gallbladder prevented expansion of the bile acid pool
      after cholesterol feeding as seen in intact rabbits because ileal bile acid
      transport did not increase. As a result, cholesterol 7alpha-hydroxylase was not
      inhibited.

PMID- 11518764
TI  - 17beta-Estradiol promotes the up-regulation of SR-BII in HepG2 cells and in rat
      livers.
AB  - The scavenger receptor class B type I (SR-BI) binds to HDL and mediates the
      selective uptake of cholesterol esters from HDL to cells. SR-BII is an
      alternatively spliced product of the SR-BI gene that only differs in the C
      terminal cytoplasmic domain. Previous studies with male mice demonstrated that SR
      BII comprises about 12% of the total SR-BI/SR-BII present in liver. In the
      current studies we used a liver cell line, HepG2, and a rat estrogen replacement
      model to examine the effects of estrogen on the expression of SR-BII. HepG2 cells
      express SR-BI but not SR-BII. SR-BI/SR-BII - blocking antibodies demonstrated
      that HepG2 cells selectively internalize cholesterol esters in a SR-BI -
      dependent manner. Incubation of HepG2 cells with 10 pM of 17beta-estradiol for 12
      h eliminated the expression of SR-BI and promoted the up-regulation of SR-BII.
      Radiolabeled HDL-binding studies demonstrated that 17beta-estradiol increased the
      number of HDL binding sites by 3-fold in HepG2 cells. However, 17beta-estradiol -
      treated cell internalized approximately 25% less cholesterol ester than vehicle
      only-treated cells. The livers obtained from male rats and ovariectomized female
      rats contained SR-BI and a small amount of SR-BII. In contrast, the livers
      obtained from intact female rats and ovariectomized female rats receiving
      estrogen replacement contained SR-BII and a small amount of SR-BI. The amount of
      SR-BI and SR-BII in adrenal tissue was not affected by any of the experimental
      treatments. We conclude that estrogen up-regulates SR-BII in HepG2 cells and rat
      liver.

PMID- 11518765
TI  - Genetic heterogeneity in the apolipoprotein C-III promoter and effects of
      insulin.
AB  - In the present study, we have investigated the in vivo and in vitro role of two
      newly identified variants (G(-)944A and A(-)1180C) located in the upstream
      promoter region of the apolipoprotein C-III (apoC-III) gene. These variants were
      studied in 30 probands diagnosed with FCHL, their relatives, and spouses. The
      allele frequencies of both variants were not different between the groups. No
      significant associations between plasma lipid traits and DNA variants were
      observed. We further analyzed the effect of the presence of these variants in the
      upstream enhancing region of the apoC-III gene, as five different in vivo
      occurring haplotypes, on the transcriptional activity of apoC-III in both HepG2
      and Caco-2 cells. All five promoter constructs, including the wild type, showed
      similar enhancing activity of the apoC-III gene. The average transcription
      efficiency was enhanced 19-fold in HepG2 cells and 11-fold in Caco-2 cells.
      Previous studies have shown in vitro insulin-dependent down-regulation of the
      apoC-III gene transcription in HepG2 cells by DNA variation in an insulin
      response element (IRE) in the apoC-III promoter. We observed a 30% insulin
      dependent down-regulation of apoC-III expression that was, however, independent
      of the presence of the two IRE variants. In contrast, in Caco-2 cells, a more
      variable insulin-dependent up-regulation was found that was also independent of
      the presence of the IRE variants.In conclusion, our data suggested that the apoC
      III gene transcription in vitro is regulated by insulin but independent of the
      presence of the two IRE variants at -455 and -482. We were unable to detect
      associations between these apoC-III variants and plasma lipids and insulin in our
      FCHL population. This means that in vivo apoC-III transcription not only depends
      upon insulin but appears to be mediated by other mechanisms.

PMID- 11518766
TI  - Dietary n-3 polyunsaturated fat increases the fractional catabolic rate of medium
      sized HDL particles in African green monkeys.
AB  - We have previously described a novel pathway for the metabolism of HDL
      subfractions in which small [2 apolipoprotein (apoA-I) molecules per particle]
      HDL particles are converted in a unidirectional manner outside the plasma
      compartment to medium (3 apoA-I molecules per particle) or large (4 apoA-I
      molecules per particle) HDL particles, which are subsequently removed from the
      circulation by the liver (Colvin et al. 1999. J. Lipid Res. 40: 1782;-1792;
      Huggins et al. 2000. J. Lipid Res. 41: 384;-394). The purpose of the present
      study was to determine whether the reduction in concentration of medium HDL in
      African green monkeys consuming n-3 polyunsaturated versus saturated fat diets
      resulted from decreased in vivo production or increased catabolism. Tracer small
      LpA-I (HDL containing only apoA-I) were isolated, without ultracentrifugation, by
      gel filtration and immunoaffinity chromatography and radiolabeled. After
      injection, the specific activity of apoA-I in small, medium, and large HDL was
      determined, and the kinetic data were analyzed using our previously published
      multicompartmental model for HDL subfraction metabolism. We found a significant
      reduction of apoA-I concentration in medium HDL in the animals fed n-3
      polyunsaturated fat (31.2 +/- 0.7 mg/dl) compared with animals fed saturated fat
      (85.4 +/- 11.9 mg/dl; P = 0.002). The production rates of apoA-I in small,
      medium, and large HDL were similar in both diet groups; however, there was a
      significant increase in the fractional catabolic rate of apoA-I in medium HDL in
      the animals fed n-3 polyunsaturated fat (2.188 +/- 0.501 pools/day) compared with
      animals fed saturated fat (0.714 +/- 0.191 pools/day; P = 0.02). We conclude that
      n-3 polyunsaturated fat reduces HDL cholesterol concentration by increasing the
      fractional catabolic rate of medium-sized HDL particles in African green monkeys.

PMID- 11518767
TI  - 12(S)-Hydroperoxy-eicosatetraenoic acid increases arachidonic acid availability
      in collagen-primed platelets.
AB  - Lipid hydroperoxides have been reported to regulate cell function and eicosanoid
      formation. The aim of the present study was to determine the effect of 12(S)
      hydroperoxy-eicosatetraenoic acid [12(S)-HPETE], the platelet 12-lipoxygenase
      derived hydroperoxide of arachidonic acid (AA), on the availability of
      nonesterified AA, which represents a rate-limiting step in the biosynthesis of
      eicosanoids. The coincubation of human platelets with concentrations of 12(S)
      HPETE below 50 nM and subthreshold concentrations (STC) of collagen (less than
      0.24 microg/ml) significantly enhanced platelet aggregation and the formation of
      thromboxane B(2), the stable catabolite of the potent aggregating agent
      thromboxane A(2). In addition, the nonesterified endogenous AA concentration
      increased by 3-fold. Arachidonoyl-containing molecular species concentrations of
      1,2-diacyl-glycero-3-phosphocholine, 1-alkyl-2-acyl-glycero-3-phosphocholine, and
      1-alkenyl-2-acyl-glycero-3-phosphoethanolamine decreased specifically in response
      to 12(S)-HPETE, whereas no significant changes were observed within 1,2-diacyl
      glycero-3-phosphoethanolamine and 1,2-diacyl-glycero-3-phosphoinositol molecular
      species. The 12(S)-HPETE-induced increase in nonesterified AA was fully prevented
      by arachidonoyl trifluoromethyl ketone, an inhibitor of cytosolic phospholipase
      A(2) (cPLA(2)), and cPLA(2) was translocated to membranes and phosphorylated in
      platelets incubated with 12(S)-HPETE. In conclusion, these results indicate that
      nanomolar concentrations of 12(S)-HPETE could play a significant role in
      controlling the level of endogenous AA and the formation of thromboxane, thereby
      potentiating platelet function.

PMID- 11518768
TI  - Scavenger receptor class B type I as a receptor for oxidized low density
      lipoprotein.
AB  - Scavenger receptor class B type I (SR-BI) has been established as the primary
      mediator of the selective transfer of lipids from HDL to mammalian cells. In
      addition to its role in cholesterol metabolism, SR-BI has been shown to bind
      apoptotic cells and thus could in theory also function as a scavenger receptor.
      We now show that SR-BI binds oxidized LDL (OxLDL) with high affinity (K(d) of 4.0
      +/- 0.5 microg/ml) and mediates internalization and degradation to an extent
      comparable to that of other scavenger receptors, when normalized to binding
      activity. The best competitors for OxLDL binding to SR-BI were oxidized
      lipoproteins, whereas native or acetylated lipoproteins only competed for a small
      fraction of OxLDL binding. Both the isolated lipids and the isolated protein from
      OxLDL bound with high affinity to SR-BI and showed partial reciprocal
      competition. Monoclonal antibody EO6, an antibody against oxidized phospholipids,
      and 1-palmitoyl-2-(5-oxovaleroyl) phosphatidylcholine (POVPC) both competed
      effectively with intact OxLDL and with isolated lipids from OxLDL for SR-BI
      binding.Together, these results demonstrate a potential function of SR-BI, in
      addition to its role in selective uptake of lipids, to mediate internalization of
      OxLDL by macrophages and suggest a central role for oxidized phospholipids in
      this process.

PMID- 11518769
TI  - Oxidized low density lipoprotein inhibits macrophage apoptosis through activation
      of the PI 3-kinase/PKB pathway.
AB  - Oxidized LDL (oxLDL) is known to induce endothelial adhesion molecule and
      monocyte chemoattractant protein 1 expression and this is thought to be involved
      in monocyte recruitment into atherosclerotic lesions. oxLDL has also been found
      to induce macrophage proliferation. The purpose of the present study was to
      determine whether oxLDL might also have the ability to increase macrophage
      populations by inhibiting apoptosis. We found that oxLDL caused a dose-dependent
      inhibition of the apoptosis that occurs in cultured bone marrow-derived
      macrophages after macrophage colony-stimulating factor (M-CSF) withdrawal without
      inducing proliferation. Incubation of macrophages with either native LDL or
      acetylated LDL had no effect on apoptosis. The prosurvival effect of oxLDL was
      not inhibited by neutralizing antibodies to granulocyte-macrophage colony
      stimulating factor, was maintained in mice homozygous for a mutation in the M-CSF
      gene, and was not due to other secreted cytokines or growth factors. oxLDL caused
      activation of the mitogen-activated protein kinases ERK1/2 (extracellular signal
      regulated kinases 1 and 2) as well as protein kinase B (PKB), a target of
      phosphatidylinositol 3-kinase (PI 3-kinase). Furthermore, there was
      phosphorylation of two important prosurvival PKB targets, I-kappaBalpha(Ser-32)
      and Bad(Ser-136). The MEK inhibitors PD 98059 and U0126 blocked ERK1/2 activation
      but did not diminish survival. Conversely, the PI 3-kinase inhibitors LY 294002
      and wortmannin blocked PKB activation, and the ability of oxidized LDL to promote
      macrophage survival. Taken together, these results indicate that oxLDL can
      directly activate a PI 3-kinase/PKB-dependent pathway that permits macrophage
      survival in the absence of growth factors.

PMID- 11518770
TI  - Monoclonal antibody detection of plasma membrane cholesterol microdomains
      responsive to cholesterol trafficking.
AB  - The hypothesis of lipid domains in cellular plasma membranes is well established.
      However, direct visualization of the domains has been difficult. Here we report
      direct visualization of plasma membrane cholesterol microdomains modulated by
      agents that affect cholesterol trafficking to and from the plasma membrane. The
      cholesterol microdomains were visualized with a monoclonal antibody that
      specifically detects ordered cholesterol arrays. These unique cholesterol
      microdomains were induced on macrophages and fibroblasts when they were enriched
      with cholesterol in the presence of an ACAT inhibitor, to block esterification of
      excess cellular cholesterol. Induction of the plasma membrane cholesterol
      microdomains could be blocked by agents that inhibit trafficking of cholesterol
      to the plasma membrane and by cholesterol acceptors that remove cholesterol from
      the plasma membrane. In addition, plasma membrane cholesterol microdomains did
      not develop in mutant Niemann-Pick type C fibroblasts, consistent with the defect
      in cholesterol trafficking reported for these cells. The induction of plasma
      membrane cholesterol microdomains on inhibition of ACAT helps explain how ACAT
      inhibition promotes cholesterol efflux from cells in the presence of cholesterol
      acceptors such as HDL. The anti-cholesterol monoclonal antibody also detected
      extracellular cholesterol-containing particles that accumulated most prominently
      during cholesterol enrichment of less differentiated human monocyte-macrophages.
      For the first time, cholesterol microdomains have been visualized that function
      in cholesterol trafficking to and from the plasma membrane.

PMID- 11518771
TI  - Lipid analysis of human HDL and LDL by MALDI-TOF mass spectrometry and (31)P-NMR.
AB  - The analysis of HDL and LDL is important for the further understanding of
      atherosclerosis because changes of the protein and lipid moieties occur under
      pathological conditions. Because destruction of lipids leads to the formation of
      well-defined products such as lysophospholipids or chlorohydrins, methods that
      allow their fast and reliable determination would be useful. In this study,
      matrix-assisted laser desorption and ionization time-of-flight mass spectrometry
      (MALDI-TOF MS) was applied for the analysis of the lipid composition of human
      lipoproteins. These data were compared with high resolution (31)P-NMR
      spectroscopy. Differences between LDL and HDL in sphingomyelin and
      phosphatidylcholine content could be monitored by NMR and mass spectrometry, and
      differences with respect to the extraction efficiency were found by MALDI-TOF MS.
      Additionally, treatment of LDL with hypochlorite and phospholipase A(2) resulted
      in marked changes (formation of chlorohydrines and lysolipids).
      Lysophosphatidylcholines were detectable by both methods, whereas MALDI-TOF MS
      failed to detect chlorohydrines of phospholipids. We conclude that MALDI-TOF MS
      provides rapidly a reliable lipid profile of lipoproteins. However, a previous
      lipid separation must be performed to detect lipid oxidation products. NMR can be
      directly applied, but suffers from lower sensitivity, and provides only limited
      information on fatty acid composition.

PMID- 11518772
TI  - Aquaporin-4 expression in adult and developing mouse and rat kidney.
AB  - Aquaporin-4 (AQP4) is a member of the aquaporin water-channel family. AQP4 is
      expressed primarily in the brain, but it is also present in the collecting duct
      of the kidney, where it is located in the basolateral plasma membrane of
      principal cells and inner medullary collecting duct (IMCD) cells. Recent studies
      in the mouse also have reported the presence of AQP4 in the basolateral membrane
      of the proximal tubule. The purpose of this study was to establish the pattern of
      AQP4 expression during kidney development and in the adult kidney of both the
      mouse and the rat. Kidneys of adult and 3-, 7-, and 15-d-old mice and rats were
      preserved for immunohistochemistry and processed using a peroxidase pre-embedding
      technique. In both the mouse and the rat, strong basolateral immunostaining was
      observed in IMCD cells and principal cells in the medullary collecting duct at
      all ages examined. Labeling was weaker in the cortical collecting duct and the
      connecting tubule, and there was no labeling of connecting tubule cells in the
      mouse. In adult mouse kidney, strong AQP4 immunoreactivity was observed in the S3
      segment of the proximal tubule. However, there was little or no labeling in the
      cortex or around the corticomedullary junction in 3- and 7-d-old mice. Between 7
      and 15 d of age, distinct AQP4 immunoreactivity appeared in the S3 segment of the
      mouse proximal tubule concomitant with the differentiation of this segment of the
      nephron. Labeling of proximal tubules was never observed in the rat kidney. These
      results suggest that there are differences in transepithelial water transport
      between mouse and rat or that additional, not yet identified water channels exist
      in the rat proximal tubule.

PMID- 11518773
TI  - Basolateral translocation by vasopressin of the aldosterone-induced pool of
      latent Na-K-ATPases is accompanied by alpha1 subunit dephosphorylation: study in
      a new aldosterone-sensitive rat cortical collecting duct cell line.
AB  - The regulation of plasma membrane Na(+)-K(+)-ATPases (NKA) expression by
      aldosterone and arginin vasopressin (AVP) in the cortical collecting duct (CCD)
      has been examined in a new rat CCD cell line, designated as RCCD(2). This cell
      line has maintained many characteristics of the CCD-in particular, the expression
      of the mineralocorticoid receptor. Mineralocorticoid receptor is expressed at the
      protein level and binds (3)H-aldosterone (approximately 15 to 20 fmol/mg
      protein). Short-circuit current (Isc) experiments showed approximately a twofold
      increase in Isc associated with a decrease in transepithelial resistance when
      cells were treated with aldosterone concentrations as low as 10(-9) M. This
      effect on Isc was significant 2 h after aldosterone addition and was still
      present after 24 h. It was accompanied by an increase in the amount of mRNA
      encoding for the alpha subunit of the epithelial sodium channel (sixfold) and the
      alpha1 subunit of NKA (fourfold) after 24 h of hormone treatment. In addition,
      mRNA expression of the serum- and glucocorticoid-induced kinase (Sgk) was
      increased by 10(-9) M aldosterone treatment as early as 45 min after hormone
      addition. As had already been documented in native CCD obtained by
      microdissection, incubation of RCCD(2) cells for 24 h with aldosterone resulted
      in the constitution of a latent pool of NKA that could be rapidly recruited by
      AVP (15 min). NKA biotinylation experiments and preparation of membrane fractions
      show that this latent pool of NKA is present in the intracellular compartment of
      the cells and is recruited by AVP in the basolateral membrane through a
      translocation process. This mechanism is accompanied by dephosphorylation of the
      alpha(1) catalytic subunit of NKA.

PMID- 11518774
TI  - Creatine transport in brush-border membrane vesicles isolated from rat kidney
      cortex.
AB  - The kidney efficiently salvages creatine from the urine; however, the
      mechanism(s) that mediates renal creatine reabsorption has not been investigated.
      This study characterizes the creatine transport mechanism in brush-border
      membrane vesicles isolated from the rat renal cortex. An osmolality plot revealed
      that creatine is transported into an osmotically active space and that it is also
      bound to the membranes. An inwardly directed NaCl gradient stimulated creatine
      uptake and the time course of uptake exhibited an overshoot phenomenon, which
      indicates the presence of an active process for creatine in these membranes. The
      uptake of creatine showed an absolute requirement for both Na(+) and Cl(-). The
      NaCl gradient-dependent creatine uptake was stimulated by a valinomycin-induced,
      inside-negative, K(+)-diffusion potential, which suggests that the uptake process
      is electrogenic. Stoichiometric analyses indicated a probable couple ratio of 2
      Na(+):1 Cl(-):1 creatine molecule. The kinetic study showed that creatine is
      transported by a high-affinity system (K(m) of 15 microM). Creatine uptake was
      inhibited by a 100-fold excess of various compounds with the following potency
      order: cold creatine = guanidinopropionic acid > nipecotic acid > gamma
      aminobutyric acid (GABA) = beta-alanine = betaine, whereas carnitine, glycine,
      taurine, and choline were without effect. This pattern of inhibition differs from
      that observed for GABA uptake (unlabeled GABA = GPA > beta-alanine > nipecotic
      acid >> creatine). The conclusion drawn was that the apical membrane of the renal
      cortical tubules contains an active, high-affinity, electrogenic, 2 Na(+)/1 Cl(
      )/creatine cotransporter.

PMID- 11518775
TI  - Endogenous endothelins mediate increased acidification in remnant kidneys.
AB  - Because endothelins (ET) mediate increased renal acidification induced by dietary
      acid and animals with reduced renal mass exhibit increased urinary ET-1
      excretion, the hypothesis that ET mediate increased renal acidification in
      remnant kidneys was tested. Four weeks before the study, rats underwent a 5/6
      nephrectomy (Nx) and a microdialysis apparatus was inserted into the remnant left
      kidney and the left kidney of sham-treated control animals, for measurements of
      renal ET-1 contents. Nx animals exhibited greater ET-1 addition to the renal
      dialysate than did control animals (681 +/- 91 versus 290 +/- 39 fmol/g kidney wt
      per min, P < 0.002) and greater urinary ET-1 excretion (346 +/- 79 versus 125 +/-
      24 fmol/d, P < 0.02). Urinary net acid excretion rates were similar for Nx and
      control animals (732 +/- 106 versus 1005 +/- 293 microEq/d, P = 0.4), but Nx
      animals exhibited greater in situ HCO(3)(-) reabsorption in proximal (972.3 +/-
      77 versus 482.6 +/- 42.4 pmol/min, P < 0.001) and distal (62.7 +/- 6.7 versus
      24.3 +/- 2.5 pmol/min, P < 0.001) tubules. Orally administered bosentan, an
      ET(A/B) receptor antagonist, decreased urinary net acid excretion in Nx animals
      (to 394 +/- 99 microEq/d, P < 0.04 versus without bosentan); the decrease was
      mediated by decreased HCO(3)(-) reabsorption in both the proximal and distal
      tubules. Furthermore, bosentan decreased blood base excess in Nx animals (0.1 +/-
      0.3 to -0.12 +/- 0.03 microM/ml blood, P < 0.002), consistent with acid
      retention. The data demonstrate that endogenous ET mediate increased urinary acid
      excretion in the remnant kidneys of Nx animals.

PMID- 11518776
TI  - Nitric oxide dependence of renal blood flow in patients with renal artery
      stenosis.
AB  - In ischemia, nitric oxide (NO) production is increased, possibly to preserve
      flow. The role of NO was investigated in hypertensive patients with or without
      renal artery stenosis (RAS). Fifty-five hypertensive patients scheduled to
      undergo diagnostic renal angiography underwent mean renal blood flow (MRBF)
      measurements before and after an intrarenal injection of the NO synthase blocker
      N(g)-monomethyl-L-arginine (L-NMMA) at 0.03 microg/kg, before angiography. A dose
      response study indicated that this dose of L-NMMA significantly blocked NO
      synthesis. MRBF was measured at baseline and 1, 5, 10, and 20 min after L-NMMA
      treatment. On the basis of the angiographic results, patients were divided into
      three diagnostic categories, i.e., essential hypertension (n = 26), unilateral
      RAS (n = 16), or bilateral RAS (n = 8). In essential hypertension, MRBF was
      decreased by 18 +/- 4% at 20 min. In unilateral RAS, L-NMMA did not affect MRBF
      in the stenotic kidney but reduced MRBF in the nonstenotic kidney by 40 +/- 9% at
      20 min. In bilateral RAS, L-NMMA reduced flow by 32 +/- 14% at 20 min. In the
      nonstenotic kidney in unilateral RAS, a positive correlation was observed between
      the effect of NO blockade on MRBF and arterial renin levels (P = 0.009). In the
      stenotic kidney, in contrast, this correlation was inverse (P = 0.007). In
      conclusion, MRBF depends on NO in hypertensive patients, except in the stenotic
      kidney in unilateral RAS. In the nonstenotic kidney in unilateral RAS, NO
      bioavailability is increased. It is suggested that a compensatory mechanism,
      regulated by NO and possibly angiotensin II, may preserve renal function.

PMID- 11518777
TI  - Dopamine D(2) receptor activation causes mitogenesis via p44/42 mitogen-activated
      protein kinase in opossum kidney cells.
AB  - This study was conducted to determine the expression of dopamine D(2)-like
      receptors in opossum kidney (OK) cells and to examine the potential role of these
      receptors in mitogenesis. First, the presence of D(2)-like receptor binding sites
      in OK cell membranes was demonstrated by radioligand binding, using
      [(3)H]spiperone. The D(2)-like receptor subtypes expressed in OK cells were
      subsequently demonstrated, by Western blotting, to be D(2), D(3), and D(4)
      receptors. OK cells were stimulated with bromocriptine, (+/-)-2-(N-phenylethyl-N
      propyl)amino-5-hydroxytetralin hydrochloride, (R)-(+)-2-dipropylamino-7-hydroxy
      1,2,3,4-tetrahydronaphthalene hydrobromide, or PD 168,077 maleate (D(2)-like,
      D(2), D(3), and D(4) receptor agonists, respectively), and mitogenesis was
      measured as a function of [(3)H]thymidine incorporation. It was observed that,
      whereas bromocriptine and (+/-)-2-(N-phenylethyl-N-propyl)amino-5-hydroxytetralin
      hydrochloride produced increases in [(3)H]thymidine incorporation, (R)-(+)-2
      dipropylamino-7-hydroxy-1,2,3,4-tetrahydronaphthalene hydrobromide and PD 168,077
      maleate did not produce such an effect, indicating the involvement of D(2)
      receptors in the mitogenic response. Pertussis toxin and PD 98059 blocked the
      mitogenesis caused by bromocriptine, suggesting a role for G(i) or G(o) proteins
      and p44/42 mitogen-activated protein kinase (MAPK), respectively. Furthermore, it
      was observed that bromocriptine produced a time-dependent increase in the
      phosphorylation (activation) of p44/42 MAPK, which was blocked by domperidone,
      pertussis toxin, or PD 98059. Therefore, this study demonstrates that, although
      OK cells express D(2), D(3), and D(4) receptors, activation of only D(2)
      receptors causes mitogenesis via phosphorylation of p44/42 MAPK. Furthermore, the
      cellular mechanisms contributing to D(2) receptor-mediated phosphorylation of
      p44/42 MAPK seem to involve the tyrosine kinase, phosphatidylinositol-3-kinase,
      and protein kinase C pathways. It is likely that bromocriptine and other
      preferential D(2) receptor agonists might provide protection against ischemic
      reperfusion injury in renal proximal tubular cells, by increasing the survival
      rates for ischemic cells.

PMID- 11518778
TI  - Expression of connective tissue growth factor in human renal fibroblasts:
      regulatory roles of RhoA and cAMP.
AB  - The induction of connective tissue growth factor (CTGF) was investigated in a
      human renal fibroblast cell line that exhibited many characteristics of primary
      human renal fibroblasts. Induction of CTGF mRNA was observed after treatment of
      the cells with transforming growth factor-beta (TGF-beta) or, even more
      prominently, lysophosphatidic acid (LPA). LPA induced a rapid transient increase
      in CTGF mRNA expression, with maximal levels being observed after 1 to 2 h. This
      increase was accompanied by CTGF protein synthesis. Induction of CTGF was
      insensitive to pertussis toxin and was not dependent on the activation of p42/44
      mitogen-activated protein kinases. Inhibition of the proteins of the Rho family
      with toxin B from Clostridium difficile abrogated basal and LPA-mediated
      induction of CTGF. Specific targeting of RhoA with C3 exotoxin or of the Rho
      kinases with the inhibitor Y-27632 similarly prevented induction of CTGF,
      implicating RhoA as a signaling module downstream of LPA. Inhibition of RhoA
      depolymerized the actin cytoskeleton, as did treatment with cytochalasin D.
      Preincubation of the human renal fibroblasts with cytochalasin D prevented
      induction of CTGF by LPA, indicating a strong contribution of an intact
      cytoskeleton. Interference with RhoA signaling similarly inhibited the induction
      of CTGF by TGF-beta. Elevation of intracellular levels of cAMP and thus
      activation of protein kinase A prevented induction of CTGF expression. The
      cytoskeletal effects of cAMP, however, were reversed by LPA. These data indicate
      complex interactions involving LPA-mediated activation of RhoA- and protein
      kinase A-dependent signaling pathways. The data thus demonstrate the regulatory
      functions of the small GTPase RhoA and of an intact cytoskeleton in the
      expression of CTGF after stimulation with LPA or TGF-beta. Analogous signal
      transduction pathways were previously demonstrated in rat mesangial cells,
      suggesting a more general role for RhoA in the regulation of CTGF expression.

PMID- 11518779
TI  - Glycosylation of circulating IgA in patients with IgA nephropathy modulates
      proliferation and apoptosis of mesangial cells.
AB  - Abnormalities in circulating IgA1 have been demonstrated in patients with IgA
      nephropathy (IgAN). This study addresses the question of the functional
      significance of this alteration in creating mesangial injury. Biologic effects of
      selected IgA glycoforms isolated from serum of IgAN patients and controls and in
      vitro deglycosylated normal IgA were tested on cultured human mesangial cells
      (MC). IgA glycoforms, ranging from 250 to 500 kD molecular weight, were isolated
      by lectin affinity chromatography followed by HPLC. IgA and IgG content was
      measured by enzyme-linked immunosorbent assay. HPLC fractions were incubated with
      MC to evaluate proliferation and apoptosis rates and nitric oxide synthesis.
      Moreover, MC were conditioned with in vitro desialylated and degalactosylated
      normal IgA. Patients with IgAN displayed increased levels of IgA glycoforms
      exposing sialic acid in alpha2,6 linkage with N-acetylgalactosamine
      (Neu5Acalpha2,6GalNAc) (P < 0.02) and GalNAc (P < 0.05), indicating truncation of
      O-linked glycans of IgA1. Moreover, IgA glycoforms with increased exposure of
      mannose were observed (P < 0.03), suggesting a defective N-linked glycosylation.
      No modification in IgG glycosylation was detected. When incubated with MC, the
      IgA glycoforms isolated from patients with increased exposure of GalNAc,
      Neu5Acalpha2,6GalNAc, or mannose, significantly depressed the proliferation and
      increased the apoptotic rate and nitric oxide synthesis activity of cultured MC,
      in comparison with fractions isolated from controls. Similarly, in vitro
      desialylated and degalactosylated IgAs significantly depressed the proliferation
      and enhanced the apoptosis rates of MC. In conclusion, a significant modulation
      of several human MC functions exerted by serum IgA with increased exposure of
      GalNAc, Neu5Acalpha2,6GalNAc, and mannose residues isolated from IgAN patients is
      reported for the first time.

PMID- 11518780
TI  - Novel paracellin-1 mutations in 25 families with familial hypomagnesemia with
      hypercalciuria and nephrocalcinosis.
AB  - Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is an
      autosomal recessive tubular disorder that is frequently associated with
      progressive renal failure. The primary defect is related to impaired tubular
      reabsorption of magnesium and calcium in the thick ascending limb of Henle's
      loop. Mutations in PCLN-1, which encodes the renal tight junction protein
      paracellin-1 (claudin-16), were identified as the underlying genetic defects.
      Comprehensive clinical data and the results of PCLN-1 mutation analysis of 25
      FHHNC families with 33 affected individuals are presented. Patients presented
      mainly with urinary tract infections, polyuria, and hematuria at a median age of
      3.5 yr. At the time of diagnosis, the GFR was already decreased to <60 ml/min per
      1.73 m(2) for 11 patients. Twelve patients exhibited progression to end-stage
      renal disease, at a median age of 14.5 yr. Treatment with magnesium salts and
      thiazides seemed to have no effect on the progression of the disease. Genotype
      analysis revealed PCLN-1 mutations in all except three mutant alleles (94%).
      Fifteen different mutations were observed, including eight novel mutations. The
      accumulation of mutations affecting the first extracellular loop was striking,
      with 48% of all mutant alleles exhibiting a Leu151Phe exchange. Haplotype
      analysis strongly suggested a founder effect among patients with FHHNC who
      originated from Germany or eastern European countries. In 13 of 23 families,
      hypercalciuria and/or nephrolithiasis were observed in otherwise unaffected
      family members, indicating a possible role of heterozygous PCLN-1 mutations in
      yielding hypercalciuric stone-forming conditions.

PMID- 11518781
TI  - Renal vascular function in hypercholesterolemia is preserved by chronic
      antioxidant supplementation.
AB  - Hypercholesterolemia impairs systemic vascular reactivity in response to
      endothelium-dependent vasodilators, which may be mediated partly through
      increased formation of lipid peroxides. However, it is unclear whether these
      pathophysiological mechanisms play a role in renal vascular impairment in
      experimental hypercholesterolemia. Hence, pigs were studied after a 3-mo normal
      (n = 7) or high cholesterol (HC) (n = 7) diet, HC diet supplemented daily with
      antioxidant vitamins E (100 IU/kg) and C (1000 mg; HC+vitamins, n = 5), or normal
      diet supplemented with vitamins (N+vitamins, n = 5). Renal blood flow was
      measured with electron-beam computed tomography before and during infusion of
      acetylcholine (Ach). Endothelial function, endothelial and inducible nitric oxide
      synthase (NOS), and nitrotyrosine immunoreactivity were studied in renal arteries
      ex vivo. Despite similar cholesterol levels, LDL oxidizability (lag time,
      malondialdehyde, and relative electrophoretic mobility) was increased in pigs
      that were fed the HC diet but was significantly decreased in pigs that were fed
      the HC+vitamins diet. Renal blood flow response to Ach was blunted in pigs that
      were fed the HC diet but was preserved in pigs that were fed the HC+vitamins
      diet. Maximal relaxation to Ach was attenuated in pigs that were fed the HC diet
      compared with those that were fed the normal diet (51.5 +/- 6.4% versus 97.0 +/-
      2.9%; P < 0.01) but was preserved in pigs that were fed the HC+vitamins diet
      (103.1 +/- 3.0%; P = 0.39) and N+vitamins diet (87.7 +/- 3.0%; P = 0.1), as were
      relaxation responses to calcium ionophore A23187. Vascular smooth-muscle
      relaxation to diethylamine was enhanced in endothelium-denuded HC vessel but was
      restored in pigs that were on the HC+vitamins regimen. In HC, immuno-reactivity
      of endothelial NOS was decreased, that of inducible NOS was increased, and both
      were preserved in pigs that were fed the HC+vitamins and N+vitamins diets,
      whereas nitrotyrosine was not detected. The present study demonstrates that
      antioxidant intervention in experimental HC reduces LDL oxidizability and
      preserves renal vascular responses to endothelium-dependent vasodilators.
      Therefore, this beneficial effect potentially can protect the kidney from
      hypercholesterolemia-induced damage.

PMID- 11518782
TI  - Increased tyrosine nitration of the brain in chronic renal insufficiency:
      reversal by antioxidant therapy and angiotensin-converting enzyme inhibition.
AB  - Interaction of reactive oxygen species with nitric oxide promotes nitric oxide
      inactivation and generation of cytotoxic reactive nitrogen species that attack
      DNA, lipids, and proteins. Nitration of free tyrosine and tyrosine residues of
      proteins results in production of nitrotyrosine, which can lead to excitotoxicity
      and frequently is found in the brain of patients and animals with various
      degenerative, ischemic, toxic, and other neurologic disorders. According to
      earlier studies, reactive oxygen species activity is increased and neuronal NO
      synthase expression in the brain is elevated in animals with chronic renal
      failure (CRF). It was hypothesized, therefore, that tyrosine nitration must be
      increased in the uremic brain. This hypothesis was tested, through determination
      of nitrotyrosine abundance (by Western blot analysis), as well as distribution
      (by immunohistology), in the cerebrum of rats with CRF 6 wk after 5/6
      nephrectomy. The results were compared with those of sham-operated controls and
      antioxidant (lazaroid)-treated and captopril-treated rats with CRF. Western blot
      analysis revealed a significant increase in nitrotyrosine abundance in the
      cerebral cortex of rats with CRF. This was accompanied by an intense
      nitrotyrosine staining of the neuronal processes, including proximal segments of
      dendrites, axons, and axon terminals of the cortical neurons. Both antioxidant
      therapy and captopril administration alleviated oxidative stress (as evidenced by
      normalization of plasma lipid peroxidation product malondialdehyde) and
      significantly reduced nitrotyrosine abundance in the cerebral cortex of the
      treated CRF group. In conclusion, CRF resulted in oxidative stress and increased
      tyrosine nitration in the cerebral cortex. Antioxidant therapy and angiotensin
      converting enzyme inhibition alleviated the CRF-induced oxidative stress and
      mitigated tyrosine nitration in the rats with CRF.

PMID- 11518783
TI  - Exacerbated inflammatory response induced by insulin-like growth factor I
      treatment in rats with ischemic acute renal failure.
AB  - In agreement with recent studies showing a deleterious effect of growth hormone
      treatment in critically ill patients, preliminary data showed that insulin-like
      growth factor I (IGF-I) administration increased the mortality rate of rats with
      ischemic acute renal failure (ARF). The present study was designed to investigate
      the mechanism responsible for this unexpected effect. Male rats with ischemic ARF
      were given subcutaneous IGF-I, 50 microg/100 g at 0, 8, and 16 h after
      reperfusion (ARF+IGF-I, n = 5) or were untreated (ARF, n = 5). A group of 5 sham
      operated rats were used as controls. Rats were killed 48 h after declamping, and
      the following studies were performed: in serum, creatinine and urea nitrogen; and
      in kidneys, histologic damage score, cellular proliferation by bromodeoxyuridine
      labeling, apoptosis by morphologic criteria, macrophage infiltration by
      immunohistochemistry using a specific antibody against ED-1, neutrophil
      infiltration by naphthol AS-D chloroacetate esterase staining, and levels of IGF
      I and IGF-I receptor mRNA by RNase protection assay. ARF and ARF+IGF-I groups had
      a severe and similar degree of renal failure. Kidney damage was histologically
      more evident in ARF+IGF-I (1.9 +/- 0.1) than in ARF (1.3 +/- 0.2) rats, and the
      number of neutrophils/mm(2) of tissue was significantly greater in ARF+IGF-I than
      in ARF rats at the corticomedullary junction (52.3 +/- 5.2 versus 37.2 +/- 4.1)
      as well as at the renal medulla (172.5 +/- 30.0 versus 42.1 +/- 9.6). No other
      differences between the groups were found. It is concluded that IGF-I treatment
      enhanced the inflammatory response in rats with ischemic ARF. Cell toxicity
      derived from increased neutrophil accumulation might play a key role in the
      greater mortality risk of critically ill patients that are treated with growth
      hormone.

PMID- 11518784
TI  - In Goodpasture's disease, CD4(+) T cells escape thymic deletion and are reactive
      with the autoantigen alpha3(IV)NC1.
AB  - Goodpasture's disease is characterized by rapidly progressive glomerulonephritis
      and pulmonary hemorrhage, in association with circulating and deposited anti
      glomerular basement membrane antibodies that recognize the alpha3 chain of type
      IV collagen [alpha3(IV)NC1] (known as the Goodpasture antigen). Unlike many other
      autoimmune diseases, recurrences are rare. In experimental models and human
      studies, both humoral and cellular mechanisms have been demonstrated to be
      involved in disease pathogenesis. However, there are few data on the
      characteristics of the autoreactive T cells or the mechanisms of tolerance to the
      autoantigen in human patients. It was demonstrated, using immunohistochemical
      analyses and reverse transcription-PCR, that the Goodpasture antigen is expressed
      in normal human thymus. Using limiting dilution analyses, the frequencies of
      circulating autoreactive T cells in patients and control subjects were assessed.
      During acute disease, there were increased frequencies of CD4(+) T cells reactive
      with alpha3(IV)NC1 (ranging from 1:6300 to 1:65,000), which decreased with time.
      There was a significant difference between patients during their acute disease
      phase and control subjects with respect to the frequency index for alpha3(IV)NC1
      specific CD4(+) T cells (P < 0.05, Mann Whitney U test). The decrease in
      autoreactive CD4(+) T-cell numbers during recovery may be the reason why
      recurrences are infrequent and may explain the loss of pathogenic autoantibodies
      with time, because of a lack of T-cell help.

PMID- 11518785
TI  - Thermal effects and blood pressure response during postdilution hemodiafiltration
      and hemodialysis: the effect of amount of replacement fluid and dialysate
      temperature.
AB  - It has been suggested that the incidence of hypotensive episodes is less with
      hemodiafiltration (HDF) than with hemodialysis (HD). The aim of the present study
      was to assess the BP response during HD and postdilution HDF in relation to the
      thermal effects of these different treatment modalities by manipulating the
      dialysate temperature (Td) during HD and the amount of replacement fluid during
      HDF. In 12 patients, energy transfer rate (in watts) and maximal decline in mean
      arterial pressure during HD at Td 37.5 degrees C, HD at Td 35.5 degrees C, and
      postdilution HDF with amounts of replacement fluids infused at room temperature
      of 1 L/h and 2.5 L/h, respectively, were assessed. All measurements were done
      twice in each patient. Energy transfer rate was comparable between HD 35.5
      degrees C (-26.61 +/- 5.33) and HDF 2.5 L/h (-25.25 +/- 7.91) and was
      significantly more negative compared with HD 37.5 degrees C (-3.53 +/- 6.44) and
      HDF 1 L/h (-15.88 +/- 6.94). The maximum decline in mean arterial pressure was
      significantly higher during HD 37.5 degrees C (-25.6 +/- 13.5) than during HD
      35.5 degrees C (-15.1 +/- 13.8) and HDF 2.5 L/h (-19.2 +/- 17.7), whereas there
      was no significant difference with HDF 1 L/h (-23.0 +/- 14.0). In conclusion,
      thermal effects during postdilution HDF are dependent on the amount of
      replacement fluid. Also during HDF, the BP response is strongly related to
      thermal effects. The use of postdilution HDF with low or intermediate amounts of
      replacement fluids infused at room temperature seems to have no advantage in
      preventing hemodynamic instability, compared with HD 35.5 degrees C.

PMID- 11518786
TI  - Increasing body fat mass in the first year of hemodialysis.
AB  - Nutritional status affects well-being and survival in patients who are undergoing
      hemodialysis. It was examined how maintenance hemodialysis altered body fat mass.
      In 72 patients with chronic renal failure (age, 62 +/- 12 yr; 42 men, 30 women),
      body fat was measured by dual x-ray absorptiometry 1 mo after initiation of
      maintenance hemodialysis and approximately 1 yr later (mean +/- SD, 11 +/- 2 mo).
      The second measurement showed significantly greater body fat mass than the first
      (11.38 +/- 3.84 versus 10.09 +/- 4.12 kg; P < 0.0001). After calculation of the
      change in body fat mass per month, no significant differences were evident in
      relation to gender or to presence of diabetes. Changes in body fat mass per month
      correlated negatively with baseline serum albumin concentration (r = -0.449, P <
      0.0001) and baseline body fat mass (r = -0.423, P < 0.001). These factors
      independently influenced the change according to multiple regression analysis
      (R(2) = 0.323, P < 0.0001). In conclusion, body fat mass increases significantly
      in the first year of maintenance hemodialysis, especially in patients with poor
      nutritional status. More general, dual x-ray absorptiometry assessment of body
      fat mass was found to be useful for evaluating the nutritional status of
      hemodialysis patients.

PMID- 11518787
TI  - Association of inflammation and malnutrition with cardiac valve calcification in
      continuous ambulatory peritoneal dialysis patients.
AB  - Cardiac valve calcification (VC) has long been regarded as a consequence of aging
      and abnormal calcium-phosphate metabolism in uremic patients. In view of the
      recent recognition of association among inflammation, malnutrition, and
      atherosclerosis, the possible role of inflammation and malnutrition in VC was
      investigated. Inflammatory markers (including C-reactive protein [CRP],
      fibrinogen, and basal metabolic rate) and nutritional status (assessed using
      serum albumin, subjective global nutrition assessment, and handgrip strength)
      were examined, in addition to calcium phosphate parameters and other traditional
      cardiovascular risk factors, including gender, smoking habits, BP, and lipid
      profile, in relation to VC in 137 patients who were on continuous ambulatory
      peritoneal dialysis. Compared with patients with no VC, patients with VC not only
      were older (60 [10] versus 54 [12] yr; P = 0.005), had higher plasma phosphate
      (1.89 [0.52] versus 1.64 [0.41] mmol/L; P = 0.003), and had higher parathyroid
      hormone (83 [40, 145] versus 38 [16, 71] pmol/L; P = 0.001) but also had higher
      CRP (4.5 [0.1, 13.4] versus 0.2 [0.1, 4.4] mg/L; P = 0.004), had higher
      fibrinogen (6.6 [1.9] versus 5.7 [1.3] g/L; P = 0.002), and had lower serum
      albumin (26 [4] versus 29 [3] g/L; P = 0004). Twenty-three percent of patients
      with VC versus 17% of patients with no VC were moderately to severely
      malnourished according to subjective global nutrition assessment (P = 0.05). Even
      after adjustment for patients' age, duration of continuous ambulatory peritoneal
      dialysis, diabetes, and calcium x phosphate product, cardiac VC remained strongly
      associated with CRP (odds ratio, 1.05; P = 0.026) and albumin (odds ratio, 0.85;
      P = 0.01). The data suggest that VC not only is a passive degenerative process
      but also involves active inflammation, similar to that seen in atherosclerosis.
      The presence of uncontrolled hyperphosphatemia and hyperparathyroidism further
      accelerates the progression of calcification. The data also indicate that VC and
      atherosclerosis should be considered as associated syndromes, sharing similar
      pathogenic mechanisms, namely active inflammation.

PMID- 11518788
TI  - Combined treatment with mycophenolate mofetil and an angiotensin II receptor
      antagonist fully protects from chronic rejection in a rat model of renal
      allograft.
AB  - Antigen-dependent and antigen-independent factors have been implicated in the
      pathophysiology of chronic allograft rejection, but their relative role is not
      well established. In the Fisher 344-->Lewis rat kidney transplant model, we
      sought (1) to compare the relative efficacy of the novel immunosuppressant,
      mycophenolate mofetil (MMF), with that of the AT1 receptor blocker, losartan, in
      preventing the development of chronic graft rejection when given for 52 wk; (2)
      to examine whether combining MMF with losartan affords better protection than
      each of the drugs alone. For comparison, the effect of cyclosporine (CsA) to
      control chronic graft rejection was also assessed. Administration of MMF alone or
      losartan alone to the kidney allografted rats resulted in a partial decrease in
      the amount of proteinuria, preservation of glomerular and tubulo-interstitial
      graft structure, limitation of intragraft cell infiltration, and improvement of
      graft survival compared with corresponding parameters in untreated, transplanted
      control rats. Combined treatment with MMF and losartan completely prevented the
      development of proteinuria, largely reduced glomerular and tubulointerstitial
      injury, and suppressed intragraft cell infiltration, and all animals survived at
      the end of the follow-up. Similarly, CsA treatment largely prevented graft injury
      but failed to achieve 100% animal survival. We have shown that MMF synergizes
      with the angiotensin II receptor antagonist, losartan, in simultaneously
      targeting complementary pathways of chronic allograft rejection. Combining MMF
      and angiotensin II receptor blocker offers superior long-term renoprotection as
      compared with CsA. Together, these findings provide the basis to prevent chronic
      injury and progressive dysfunction after renal transplantation.

PMID- 11518789
TI  - An increase in myeloid-related protein serum levels precedes acute renal
      allograft rejection.
AB  - Upon interaction with activated endothelium, monocytes and neutrophils form
      complexes of myeloid-related protein 8 (MRP8) (S100A8) and MRP14 (S100A9), two
      members of the calcium-binding S100 family that are secreted during
      transendothelial migration. In a pilot study of 20 renal transplant recipients
      and a validation study of 36 renal transplant recipients, MRP8/14 serum levels
      were measured with an enzyme-linked immunosorbent assay for 28 d, associated with
      C-reactive protein and creatinine serum levels, and grouped according to biopsy
      proven acute rejection. Serum levels of MRP8/14 but not C-reactive protein were
      significantly increased for several days during the first 2 wk for the acute
      rejection groups in both studies (P < 0.005, on day 6 after transplantation). As
      determined by using receiver operating characteristic curves, the optimal cutoff
      for 100% specificity and high sensitivity (67%) for acute rejection on day 6
      after transplantation was calculated to be 4.2 microg/ml for MRP8/14 in the pilot
      study; this value was confirmed in the validation study. Positive MRP8/14 serum
      levels preceded acute rejection episodes by a median of 5 d. A 3-d course of
      intravenous methylprednisolone therapy reduced prerejection MRP8/14 serum levels
      from 5.7 microg/ml to 3.3 microg/ml (P < 0.05). All MRP8/14 serum levels were
      below the cutoff during urinary tract infections, delayed graft function, or
      cytomegalovirus infections, and these values did not differ significantly from
      control values. It is concluded that the MRP8/14 complex is a very early serum
      marker suitable for monitoring of acute rejection with high sensitivity and
      specificity.

PMID- 11518790
TI  - Angiotensin-converting enzyme inhibition induces apoptosis in erythroid
      precursors and affects insulin-like growth factor-1 in posttransplantation
      erythrocytosis.
AB  - A number of studies suggest that erythropoietin (Ep), angiotensin II, and insulin
      like growth factor (IGF-1) are involved in the pathogenesis of
      posttransplantation erythrocytosis (PTE). Angiotensin-converting enzyme
      inhibitors (ACEI) are the treatment of choice in PTE, but their mechanism of
      action is unclear. It was shown previously that ACEI added directly to cultures
      of erythroid precursors from patients with PTE inhibit colony growth. In this
      report, the effect of ACEI on CD34+ erythroid precursor apoptosis was studied, as
      were hematocrit (Hct), Ep, IGF-1, and IGF-binding protein 3 (IGF-BP3) levels. Ten
      patients with PTE, 10 transplant control patients, and 7 normal control subjects
      were studied. Peripheral blood CD34+ cells were isolated, and apoptosis was
      assessed by annexin assay and DNA laddering before and during ACEI therapy. At
      the same time, Hct, Ep, IGF-1, and IGF-BP3 levels were measured. Baseline CD34+
      cell number, CD34+ apoptosis, Ep, IGF-1, and IGF-BP3 levels were the same between
      PTE and transplant control subjects. ACEI therapy was associated with a striking
      increase in CD34+ cell apoptosis and a decrease in Hct in both groups. In
      contrast to control subjects, patients with PTE on ACEI showed a significant
      decrease in IGF-1 levels and a greater percentage decrease in Hct. In normal
      control subjects, ACEI therapy was associated with a fall in Hct but no change in
      CD34+ cell apoptosis. In PTE, ACEI-related increase in erythroid progenitor
      apoptosis may partially explain the ACEI-associated decrease in Hct. However, it
      is not clear that erythroid precursor apoptosis is related to changes in IGF-1 or
      IGF-BP3.

PMID- 11518791
TI  - Decreased sensitivity of distal nephron and collecting duct to parathyroid
      hormone in pseudohypoparathyroidism type I.
AB  - Parathyroid hormone (PTH) transiently increases urinary excretion of the
      lysosomal enzyme, N-acetyl-beta-D-glucosaminidase, which is distributed mainly in
      proximal tubules. The response is reduced in pseudohypoparathyroidism (PHP) type
      I, which is characterized by target-organ resistance to PTH. Evidenced by normal
      calcium resorption, distal tubule sensitivity to PTH has been believed to be
      normal in this disorder. This hypothesis was tested through a search for another
      marker of distal nephron sensitivity to PTH. In the human kidney, cathepsin D was
      expressed predominantly in distal segments of the nephron, cortical and medullary
      thick ascending limbs of Henle's loop, distal convoluted tubules, and connecting
      tubules and in cortical collecting ducts and medullary collecting ducts. PTH
      infusion transiently increased cathepsin D excretion in normal subjects. The
      cathepsin D response to PTH was reduced in the patients with PHP type I. The
      decrease in cathepsin D response in PHP type I indicates a resistance to PTH in
      the distal nephron (cortical thick ascending limbs of Henle's loop, distal
      convoluted tubules, and connecting tubules) and cortical collecting ducts. These
      observations suggest that the preservation of renal tubular sensitivity to PTH in
      this disorder may be confined to PTH-dependent calcium resorption in distal
      tubules.

PMID- 11518792
TI  - 2000 Presidential address.

PMID- 11518793
TI  - Adynamic renal osteodystrophy: is there a problem?

PMID- 11518794
TI  - The primary hyperoxalurias.

PMID- 11518795
TI  - Recurrence of idiopathic nephrotic syndrome after renal transplantation. 1972.

PMID- 11518796
TI  - Endoplasmic reticulum stress prolongs GH-induced Janus kinase (JAK2)/signal
      transducer and activator of transcription (STAT5) signaling pathway.
AB  - The desensitization of the GH-induced Janus kinase 2 (JAK2) and signal transducer
      and activator of transcription 5 (STAT5) signaling pathway plays a crucial role
      in GH regulation of hepatic genes. Previous studies have demonstrated that the
      inactivation of the GH-induced JAK2/STAT5 pathway is regulated by protein
      translation and suppressors of cytokine signaling (SOCS). In this study we sought
      to explore the relationships between endoplasmic reticulum stress, GH-induced
      JAK2/STAT5 activity and SOCS expression. 1,2-bis(o-Aminophenoxy)ethane-N,N,N,N
      tetraacetic acid (acetoxymethyl)ester (BAPTA-AM), used to provoke endoplasmic
      reticulum stress, caused a drastic inhibition of protein translation that
      correlated with the phosphorylation of the eukaryotic translation initiation
      factor 2alpha. Both GH and BAPTA-AM caused a rapid induction of the transcription
      factor C/EBP homology protein (CHOP) and an additive effect was observed with
      combined treatment, which suggests a regulatory role of GH on endoplasmic
      reticulum stress. Endoplasmic reticulum stress did not interfere with the rapid
      GH activation of STAT5 DNA binding activity. However, BAPTA-AM prolonged the DNA
      binding activity of STAT5 without affecting STAT5 or JAK2 protein levels. GH
      induced phosphorylation of JAK2 and STAT5 DNA binding activity were prolonged in
      the presence of BAPTA-AM, suggesting that endoplasmic reticulum stress prevents
      the inactivation of STAT5 DNA binding activity by modulating the rate of
      JAK2/STAT5 dephosphorylation. Like BAPTA-AM, the endoplasmic reticulum stressors
      dithiothreitol and A23187 also prolonged the GH-induced STAT5 DNA binding
      activity. We were not able to correlate BAPTA-AM effects to the GH-dependent
      expression of SOCS proteins or SOCS mRNA, suggesting that endoplasmic reticulum
      stress modulates the rate of JAK2/STAT5 dephosphorylation through mechanisms
      other than inhibition of SOCS expression. This study indicates that cellular
      stress may modulate transcription through the JAK/STAT pathway.

PMID- 11518797
TI  - Regulation of Pit-1 expression by ghrelin and GHRP-6 through the GH secretagogue
      receptor.
AB  - GH secretagogues are an expanding class of synthetic peptide and nonpeptide
      molecules that stimulate the pituitary gland to secrete GH through their own
      specific receptor, the GH-secretagogue receptor. The cloning of the receptor for
      these nonclassical GH releasing molecules, together with the more recent
      characterization of an endogenous ligand, named ghrelin, have unambiguously
      demonstrated the existence of a physiological system that regulates GH secretion.
      Somatotroph cell-specific expression of the GH gene is dependent on a pituitary
      specific transcription factor (Pit-1). This factor is transcribed in a highly
      restricted manner in the anterior pituitary gland. The present experiments sought
      to determine whether the synthetic hexapeptide GHRP-6, a reference GH
      secretagogue compound, as well as an endogenous ligand, ghrelin, regulate pit-1
      expression. By a combination of Northern and Western blot analysis we found that
      GHRP-6 elicits a time- and dose-dependent activation of pit-1 expression in
      monolayer cultures of infant rat anterior pituitary cells. This effect was
      blocked by pretreatment with actinomycin D, but not by cycloheximide, suggesting
      that this action was due to direct transcriptional activation of pit-1. Using an
      established cell line (HEK293-GHS-R) that overexpresses the GH secretagogue
      receptor, we showed a marked stimulatory effect of GHRP-6 on the pit-1 -2,500 bp
      5'-region driving luciferase expression. We truncated the responsive region to 
      231 bp, a sequence that contains two CREs, and found that both CREs are needed
      for GHRP-6-induced transcriptional activation in both HEK293-GHS-R cells and
      infant rat anterior pituitary primary cultures. The effect was dependent on PKC,
      MAPK kinase, and PKA activation. Increasing Pit-1 by coexpression of pCMV-pit-1
      potentiated the GHRP-6 effect on the pit-1 promoter. Similarly, we showed that
      the endogenous GH secretagogue receptor ligand ghrelin exerts a similar effect on
      the pit-1 promoter. These data provide the first evidence that ghrelin, in
      addition to its previously reported GH-releasing activities, is also capable of
      regulating pit-1 transcription through the GH secretagogue receptor in the
      pituitary, thus giving new insights into the physiological role of the GH
      secretagogue receptor on somatotroph cell differentiation and function.

PMID- 11518798
TI  - AR suppresses transcription of the alpha glycoprotein hormone subunit gene
      through protein-protein interactions with cJun and activation transcription
      factor 2.
AB  - Previously, we reported that the AR directly suppressed transcription of the
      alpha glycoprotein hormone subunit (alphaGSU) gene in a ligand-dependent fashion
      while ER had no effect. Mutagenesis studies of the alphaGSU promoter indicated
      that two elements were required for AR-mediated suppression: the alpha basal
      element and tandem cAMP response elements (CREs). Because several members of the
      bZip family of transcriptional proteins can bind the CREs, we used several
      functional assays to determine whether AR interacts selectively with cJun,
      activation transcription factor 2 (ATF2), or CRE binding protein (CREB). When
      tested by cotransfection with AR, cJun and ATF2 specifically rescued androgen
      mediated suppression of the alphaGSU-reporter construct in a gonadotrope-derived
      cell line. In contrast, cotransfected CREB displayed no activity in this rescue
      assay. In fact, overexpression of CREB alone diminished activity of the alphaGSU
      promoter, suggesting that the transcriptional activity normally conferred by the
      tandem CREs in gonadotropes requires their occupancy by cJun/ATF2 heterodimers.
      Binding assays carried out with a glutathione-S-transferase-AR fusion protein
      indicated that the receptor itself also displayed a clear preference for binding
      cJun and ATF2. Furthermore, we ruled out the possibility that AR suppressed
      activity of the alphaGSU promoter by reducing synthesis of these bZip proteins.
      Additional experiments suggested that phosphorylation of AR or histone
      acetylation are unlikely requirements for AR suppression of alphaGSU promoter
      activity. Thus, our data suggest that AR suppresses activity of the alphaGSU
      promoter through direct protein-protein interactions with cJun and ATF2.

PMID- 11518799
TI  - AR suppresses transcription of the LHbeta subunit by interacting with
      steroidogenic factor-1.
AB  - Synthesis of LH is suppressed by feedback from gonadal steroids. Previously, we
      demonstrated that 779 bp of the bovine LHbeta promoter was sufficient to target
      expression of a chloramphenicol acetyltransferase reporter gene specifically to
      the pituitary in transgenic mice, and found that it was appropriately suppressed
      after administration of T or E2. In this study, we report that ligand-bound AR,
      but not ligand-bound ER, directly suppressed activity of the bovine LHbeta
      promoter when examined in a gonadotrope-derived cell line. Additional studies
      with mutated bovine LHbeta promoter constructs focused on the proximal 5'
      flanking region because of the presence of several cis-acting elements that are
      highly conserved across all mammals. These include regulatory elements that bind
      steroidogenic factor 1 (SF-1), Egr-1, and Pitx1. When tested by cotransfection
      with AR, overexpression of Egr-1, Pitx1, and constitutively active steroidogenic
      factor 1 (SF-1DeltaLBD) each individually rescued androgen-mediated suppression
      of the bovine LHbeta promoter. This suggested a functional interaction between
      each of these transcription proteins and AR. In contrast, overexpression of full
      length SF-1 was incapable of relieving the bovine LHbeta promoter from the
      suppressive effect imposed by AR. This suggested that the ligand-binding domain
      of SF-1 plays an important role in functional interactions that occur between
      this protein and AR. This notion was further supported by binding assays
      performed with glutathione-S-transferase-AR: these identified SF-1 as a key
      interactive partner and localized this interaction to the ligand-binding domain
      of the protein. Additional binding studies indicated that protein interactions
      between SF-1, Pitx1, and Egr-1 interfere with formation of a binary complex that
      contains AR and SF-1. Thus, we conclude that AR suppresses activity of the bovine
      LHbeta promoter through protein-protein interactions with SF-1 and that the
      degree of this interaction can be modified by the presence of Egr-1 and Pitx1.

PMID- 11518800
TI  - Fibroblast growth factor activation of the rat PRL promoter is mediated by
      PKCdelta.
AB  - Fibroblast growth factors play a critical role in cell growth, development, and
      differentiation and are also implicated in the formation and progression of
      tumors in a variety of tissues including pituitary. We have previously shown that
      fibroblast growth factor activation of the rat PRL promoter in GH4T2 pituitary
      tumor cells is mediated via MAP kinase in a Ras/Raf-1-independent manner. Herein
      we show using biochemical, molecular, and pharmacological approaches that
      PKCdelta is a critical component of the fibroblast growth factor signaling
      pathway. PKC inhibitors, or down-regulation of PKC, rendered the rat PRL promoter
      refractory to subsequent stimulation by fibroblast growth factors, implying a
      role for PKC in fibroblast growth factor signal transduction. FGFs caused
      specific translocation of PKCdelta from cytosolic to membrane fractions,
      consistent with enzyme activation. In contrast, other PKCs expressed in GH4T2
      cells (alpha, betaI, betaII, and epsilon) did not translocate in response to
      fibroblast growth factors. The PKCdelta subtype-selective inhibitor, rottlerin,
      or expression of a dominant negative PKCdelta adenoviral construct also blocked
      fibroblast growth factor induction of rat PRL promoter activity, confirming a
      role for the novel PKCdelta isoform. PKC inhibitors selective for the
      conventional alpha and beta isoforms or dominant negative PKCalpha adenoviral
      expression constructs had no effect. Induction of the endogenous PRL gene was
      also blocked by adenoviral dominant negative PKCdelta expression but not by an
      analogous dominant negative PKCalpha construct. Finally, rottlerin significantly
      attenuated FGF-induced MAP kinase phosphorylation. Together, these results
      indicate that MAP kinase-dependent fibroblast growth factor stimulation of the
      rat PRL promoter in pituitary cells is mediated by PKCdelta.

PMID- 11518802
TI  - Aberrant alternative splicing of thyroid hormone receptor in a TSH-secreting
      pituitary tumor is a mechanism for hormone resistance.
AB  - Patients with TSH-secreting pituitary tumors (TSHomas) have high serum TSH levels
      despite elevated thyroid hormone levels. The mechanism for this defect in the
      negative regulation of TSH secretion is not known. We performed RT-PCR to detect
      mutations in TRbeta from a surgically resected TSHoma. Analyses of the RT-PCR
      products revealed a 135-bp deletion within the sixth exon that encodes the ligand
      binding domain of TRbeta2. This deletion was caused by alternative splicing of
      TRbeta2 mRNA, as near-consensus splice sequences were found at the junction site
      and no deletion or mutations were detected in the tumoral genomic DNA. This
      TRbeta variant (TRbeta2spl) lacked thyroid hormone binding and had impaired T3
      dependent negative regulation of both TSHbeta and glycoprotein hormone alpha
      subunit genes in cotransfection studies. Furthermore, TRbeta2spl showed dominant
      negative activity against the wild-type TRbeta2. These findings strongly suggest
      that aberrant alternative splicing of TRbeta2 mRNA generated an abnormal TR
      protein that accounted for the defective negative regulation of TSH in the
      TSHoma. This is the first example of aberrant alternative splicing of a nuclear
      hormone receptor causing hormonal dysregulation. This novel posttranscriptional
      mechanism for generating abnormal receptors may occur in other hormone-resistant
      states or tumors in which no receptor mutation is detected in genomic DNA.

PMID- 11518803
TI  - Activation of MAPK by TRH requires clathrin-dependent endocytosis and PKC but not
      receptor interaction with beta-arrestin or receptor endocytosis.
AB  - To determine whether the interaction of the TRH receptor with beta-arrestin is
      necessary for TRH activation of MAPK, cells expressing either intact or
      truncated, internalization-defective TRH receptors were transfected with a beta
      arrestin-green fluorescent protein conjugate. In cells expressing the wild-type
      pituitary TRH receptor, TRH caused translocation of the beta-arrestin-green
      fluorescent protein conjugate from the cytosol to the plasma membrane within 30
      sec. After 5 min, the beta-arrestin-green fluorescent protein conjugate was
      visible in vesicles, where it colocalized with rhodamine-labeled TRH. In
      hypertonic sucrose, the beta-arrestin-green fluorescent protein conjugate
      translocated to the plasma membrane after TRH addition but did not internalize.
      In cells expressing the truncated TRH receptor, TRH did not cause translocation
      of the beta-arrestin-green fluorescent protein conjugate. TRH activated MAPK
      strongly in cells expressing intact or truncated TRH receptors, indicating that
      the receptor does not need to bind beta-arrestin or internalize. MAPK activation
      by TRH, epidermal growth factor, and phorbol ester was strongly inhibited by
      hypertonic sucrose and concanavalin A, which block movement of proteins into
      coated pits and coated pit assembly. Hypertonic sucrose did not affect MAPK
      activation in cells overexpressing MAPK kinase 1. Dominant negative dynamin,
      which blocks conversion of coated pits to vesicles, also reduced receptor
      internalization and TRH activation of MAPK. TRH activation of MAPK required PKC
      but was insensitive to pertussis toxin and did not require ras, epidermal growth
      factor receptor kinase, or PI3K. These results show that the TRH receptor itself
      does not need to bind beta-arrestin or undergo sequestration to activate MAPK but
      that the endocytic pathway must be intact.

PMID- 11518805
TI  - IGF-I causes an ultrasensitive reduction in GH mRNA levels via an extracellular
      mechanism involving IGF binding proteins.
AB  - IGF-I-dependent decreases in endogenous GH mRNA expression were studied in
      individual rat MtT/S somatotroph cells using in situ hybridization. It was first
      shown that increasing IGF-I concentrations (0-90 nM) decreased GH mRNA levels in
      a ultrasensitive manner when averaged over the entire population, such that the
      decrease occurred over a narrow range of IGF-I concentration with an EC50 of 7.1
      nM. The degree of ultrasensitivity of the population average was expressed by
      calculating the Hill coefficient (nA), which had a value of -2.0. GH mRNA levels
      in individual dispersed cells from these cultures were then measured. These
      results were first summed for all cells to show that the average response of the
      population remained ultrasensitive (nA = -2.6, EC50 = 8.1 nM). Then, parameters
      for individual cells of the population were calculated using mathematical
      modeling of the distribution of individual cell GH mRNA levels after treatment
      with 0-90 nM IGF-I. Solution of the data from the individual cells yielded a Hill
      coefficient (nI = -0.65) and a heterogeneity coefficient (mI = -1.2) indicative
      of individual cell responsiveness to IGF-I that was not ultrasensitive and very
      heterogeneous. These results suggested that ultrasensitivity in the population
      may likely be caused by an extracellular mechanism regulating IGF-I
      concentrations, such as IGF binding proteins. Increasing concentrations of long
      (Arg)3IGF-1, an analog that binds the IGF type-1 receptor but not IGF binding
      proteins, showed a linear inhibition of GH mRNA levels. Treatment with IGF
      binding protein ligand inhibitor, an IGF-I analog that binds to IGF binding
      proteins but not the IGF type-1 receptor, decreased GH mRNA levels in the absence
      of exogenous IGF-I. Thus, IGF binding proteins provide the extracellular
      sequestration of IGF-I necessary for the precise and ultrasensitive regulation of
      GH mRNA levels in the entire cell population, although expression within
      individual cells is regulated in a graded fashion.

PMID- 11518806
TI  - Glucose-dependent insulinotropic polypeptide is a growth factor for beta (INS-1)
      cells by pleiotropic signaling.
AB  - Activation of the G-protein-coupled receptor for glucose-dependent insulinotropic
      polypeptide facilitates insulin-release from pancreatic beta-cells. In the
      present study, we examined whether glucose-dependent insulinotropic polypeptide
      also acts as a growth factor for the beta-cell line INS-1. Here, we show that
      glucose-dependent insulinotropic polypeptide induced cellular proliferation
      synergistically with glucose between 2.5 mM and 15 mM by pleiotropic activation
      of signaling pathways. Glucose-dependent insulinotropic polypeptide stimulated
      the signaling modules of PKA/cAMP regulatory element binder, MAPK, and
      PI3K/protein kinase B in a glucose- and dose-dependent manner. Janus kinase 2 and
      signal transducer and activators of transcription 5/6 pathways were not
      stimulated by glucose-dependent insulinotropic polypeptide. Activation of PI3K by
      glucose-dependent insulinotropic polypeptide and glucose was associated with
      insulin receptor substrate isoforms insulin receptor substrate-2 and growth
      factor bound-2 associated binder-1 and PI3K isoforms p85alpha, p110alpha,
      p110beta, and p110gamma. Downstream of PI3K, glucose-dependent insulinotropic
      polypeptide-stimulated protein kinase Balpha and protein kinase Bbeta isoforms
      and phosphorylated glycogen synthase kinase-3, forkhead transcription factor
      FKHR, and p70S6K. These data indicate that glucose-dependent insulinotropic
      polypeptide functions synergistically with glucose as a pleiotropic growth factor
      for insulin-producing beta-cells, which may play a role for metabolic adaptations
      of insulin-producing cells during type II diabetes.

PMID- 11518807
TI  - Conservation of signaling pathways of xenobiotic-sensing orphan nuclear
      receptors, chicken xenobiotic receptor, constitutive androstane receptor, and
      pregnane X receptor, from birds to humans.
AB  - Chicken xenobiotic receptor, pregnane X receptor, and constitutive androstane
      receptor are orphan nuclear receptors that have recently been discovered to
      regulate drug- and steroid-mediated induction of hepatic cytochromes P450 (CYP).
      This induction is part of an adaptive response involving numerous genes to
      exposure to drugs and chemicals and has major clinical and toxicological
      implications. Here we report experiments in the chicken hepatoma cell line LMH
      that suggest evolutionary conservation of the signaling pathways triggered by
      pregnane X receptor, constitutive androstane receptor, and chicken xenobiotic
      receptor. Thus, the phenobarbital-inducible enhancer units of the mouse Cyp2b10,
      rat CYP2B2, and human CYP2B6 genes were activated in reporter gene assays by the
      same compounds that activate the chicken CYP2H1 phenobarbital-inducible enhancer
      units. Chicken xenobiotic receptor, pregnane X receptor, and constitutive
      androstane receptor all bound to the CYP2H1 phenobarbital-inducible enhancer
      units in gel-shift experiments. In CV-1 cell transactivation assays, mammalian
      pregnane X receptors activate the chicken phenobarbital-inducible enhancer units
      to the same extent as does chicken xenobiotic receptor, each receptor maintaining
      its species-specific ligand spectrum. To assess the reported role of protein
      phosphorylation in drug-mediated induction, we treated LMH cells with okadaic
      acid and observed increased mRNA of delta-aminolevulinate synthase and CYP2H1
      whereas expression of CYP3A37 was decreased. The effects of okadaic acid and
      other modifiers of protein phosphorylation in LMH cells are comparable to those
      seen on CYP2Bs and CYP3As in mammalian primary hepatocyte cultures. These results
      indicate that closely related nuclear receptors, transcription factors, and
      signaling pathways are mediating the transcriptional activation of multiple genes
      by xenobiotics in chicken, rodents, and man.

PMID- 11518808
TI  - A new human MR splice variant is a ligand-independent transactivator modulating
      corticosteroid action.
AB  - Aldosterone effects are mediated by the MR, which possesses the same affinity for
      mineralocorticoids and glucocorticoids. In addition to the existence of
      mechanisms regulating intracellular hormone availability, we searched for human
      MR splice variants involved in tissue-specific corticosteroid function. We have
      identified a new human MR isoform, hMRDelta5,6, resulting from an alternative
      splicing event skipping exons 5 and 6 of the human MR gene. hMRDelta5,6 mRNAs are
      expressed in several human tissues at different levels compared with wild-type
      human MR, as shown by real time PCR. Introduction of a premature stop codon
      results in a 75-kDa protein lacking the entire hinge region and ligand binding
      domain. Interestingly, hMRDelta5,6 is still capable of binding to DNA and acts as
      a ligand-independent transactivator, with maximal transcriptional induction
      corresponding to approximately 30-40% of aldosterone-activated wild-type human
      MR. Coexpression of hMRDelta5,6 with human MR or human GR increases their
      transactivation potential at high doses of hormone. Finally, hMRDelta5,6 is able
      to recruit the coactivators, steroid receptor coactivator 1, receptor interacting
      protein 140, and transcription intermediary factor 1alpha, which enhance its
      transcriptional activity. Ligand-independent transactivation and enhancement of
      both wild-type MR and GR activities by hMRDelta5,6 suggests that this new variant
      might play a role in modulating corticosteroid effects in target tissues.

PMID- 11518809
TI  - Novel N-terminal variant of human VDR.
AB  - The importance of N-terminal regions of nuclear hormone receptors in
      transcriptional regulation is increasingly recognized. As variant VDR gene
      transcripts indicated possible N-terminally extended receptors, we investigated
      their natural occurrence, transactivation capacity, and subcellular localization.
      A novel 54-kDa VDRB1 protein, in addition to the previously recognized 48-kDa
      VDRA form, was detected in human kidney tissue as well as in osteoblastic (MG63),
      intestinal (Int-407, DLD-1, and COLO 206F), and kidney epithelial (786) human
      cell lines by Western blots using isoform-specific and nonselective anti-VDR
      antibodies. VDRB1 was present at approximately one-third the level of VDRA.
      Isoform-specific VDRB1 expression constructs produced lower ligand-dependent
      transactivation than VDRA when transiently transfected with a vitamin D
      responsive promoter into cell lines with low endogenous VDR. Intracellular
      localization patterns of the green fluorescent protein-tagged VDR isoforms
      differed. VDRB1 appeared as discrete intranuclear foci in the absence of 1,25
      dihydroxyvitamin D3, whereas VDRA produced diffuse nuclear fluorescence. After
      1,25-dihydroxyvitamin D3 treatment, both VDR isoforms exhibited similar diffuse
      nuclear signal. In the absence of 1,25-dihydroxyvitamin D3, the VDRB1 foci
      partially colocalized with SC-35 speckles and a subset of promyelocytic leukemia
      nuclear bodies. These data provide the first evidence of VDRB1, a novel N
      terminally variant human VDR that is expressed at a level comparable to VDRA in
      human tissue and cell lines. It is characterized by reduced transactivation
      activity and a ligand-responsive speckled intranuclear localization. The
      intranuclear compartmentalization and altered functional activity of VDRB1 may
      mediate a specialized physiological role for this receptor isoform.

PMID- 11518810
TI  - Apoptosis of granulosa cells and female infertility in achondroplastic mice
      expressing mutant fibroblast growth factor receptor 3G374R.
AB  - Fibroblast growth factors play an important role in the control of ovarian
      folliculogenesis, but the complete repertoire of ovarian receptors which can
      transduce the fibroblast growth factor signals and their precise localization in
      the ovary have not yet been characterized. The most common form of inherited
      human dwarfism results from a point mutation in the transmembrane region of
      fibroblast growth factor receptor 3. A mouse model for achondroplasia was
      generated by introducing the human mutation (glycine 380-arginine) into the mouse
      fibroblast growth factor receptor 3 (G374R) by a "knock-in" approach using gene
      targeting leading to a constitutively active receptor. This resulted in the
      development of dwarf mice that share many features with human achondroplasia.
      Here we report that female (fibroblast growth factor receptor 3 G374R) dwarf mice
      become infertile. While no significant changes were observed in the anatomical
      and histological appearance of ovaries of 3-wk-old dwarf mice, a dramatic
      difference was observed in ovaries of 3-month-old mice. The normal ovary consists
      mainly of healthy corpora lutea and follicles at different stages of development,
      whereas the ovaries of the dwarf mice remain small and contain mainly follicles
      with a progressive apoptosis in the granulosa cells, and no corpora lutea could
      be observed. The levels of LH, FSH, and progesterone were lower by 72.3%, 38.0%,
      and 40.0%, respectively, in the blood of the dwarf mice compared with normal
      mice, and the total bioactivity of pituitary FSH and LH was lower by 65.6% and
      79.6%, respectively, in the dwarf mice compared with normal mice. However
      treatment with PMSG and human CG of the dwarf mice led to rapid follicular
      development and formation of corpora lutea. Interestingly, the expression of the
      tumor suppressor gene p53 was increased dramatically in ovaries of the dwarf
      mice. The presence of the fibroblast growth factor receptor 3 cellular receptors
      in both normal and dwarf animals was demonstrated by Western blot and
      immunostaining. However, the distribution of the fibroblast growth factor
      receptors in the two strains shows significant differences. In the normal ovaries
      fibroblast growth factor receptor 3 was homogeneously distributed on the cell
      membrane of the granulosa cells and was absent in theca as well as corpora lutea
      cells, whereas in dwarf mice ovaries it was highly clustered on granulosa cells
      and very often appears in endocytic vesicles. Aged oocytes were more frequently
      observed in preantral follicles of ovaries of the dwarf mice. Nevertheless,
      oocytes isolated from antral follicles resume their meiotic division at a high
      percentage, similar to oocytes obtained from normal ovaries. The results imply
      fibroblast growth factor receptor 3 involvement in the control of follicular
      development through regulation of granulosa cell growth and differentiation, and
      that unovulation in the dwarf mice could be overcome in part by administration of
      exogenous gonadotropins. Moreover, it is suggested that the infertile phenotype
      is partially due to defects in the pituitary-gonadal axis.

PMID- 11518811
TI  - Identification of two distinct structural motifs that, when added to the C
      terminal tail of the rat LH receptor, redirect the internalized hormone-receptor
      complex from a degradation to a recycling pathway.
AB  - We show that most of the internalized rat LH receptor is routed to a lysosomal
      degradation pathway whereas a substantial portion of the human LH receptor is
      routed to a recycling pathway. Chimeras of these two receptors identified a
      linear amino acid sequence (GTALL) present near the C terminus of the human LH
      receptor that, when grafted onto the rat LH receptor, redirects most of the rat
      LH receptor to a recycling pathway. Removal of the GTALL sequence from the human
      LH receptor failed to affect its routing, however. The GTALL sequence shows
      homology with the C-terminal tetrapeptide (DSLL) of the beta2-adrenergic
      receptor, a motif that has been reported to mediate the recycling of the
      internalized beta2-adrenergic receptor by binding to ezrin-radixin-moesin-binding
      phosphoprotein-50. Addition of the DSLL tetrapeptide to the C terminus of the rat
      LH receptor also redirects most of the internalized rat LH receptor to a
      recycling pathway but, like the recycling of the human LH receptor, this
      rerouting is not mediated by ezrin-radixin-moesin-binding phosphoprotein-50. We
      conclude that most of the internalized rat LH receptor is degraded because its C
      terminal tail lacks motifs that promote recycling and that two distinct, but
      homologous, motifs (DSLL at the C terminus or GTALL near the C terminus) can
      reroute the internalized rat LH receptor to a recycling pathway that is
      independent of ezrin-radixin-moesin-binding phosphoprotein-50.

PMID- 11518812
TI  - Modulation of endogenous GATA-4 activity reveals its dual contribution to
      Mullerian inhibiting substance gene transcription in Sertoli cells.
AB  - Secretion of Mullerian inhibiting substance by fetal Sertoli cells is essential
      for normal male sex differentiation since it induces regression of the Mullerian
      ducts in the developing male embryo. Proper spatiotemporal expression of the MIS
      gene requires a specific combination of transcription factors, including the zinc
      finger factor GATA-4 and the nuclear receptor steroidogenic factor-1, which both
      colocalize with Mullerian inhibiting substance in Sertoli cells. To establish the
      molecular mechanisms through which GATA-4 contributes to MIS transcription, we
      have generated and characterized novel GATA-4 dominant negative competitors. The
      first one, which consisted solely of the GATA-4 zinc finger DNA-binding domain,
      was an efficient competitor of GATA transcription mediated both by direct GATA
      binding to DNA and protein-protein interactions involving GATA factors. The
      second type of competitor consisted of the same GATA-4 zinc finger DNA-binding
      domain but harboring mutations that prevented DNA binding. This second class of
      competitors repressed GATA-dependent transactivation by specifically competing
      for GATA protein-protein interactions without affecting the DNA-binding activity
      of endogenous GATA factors. These competitors, along with the GATA-4 cofactor FOG
      2 (friend of GATA-2), were used to specifically modulate endogenous GATA-4
      activity in Sertoli cells. Our results indicate that GATA-4 contributes to MIS
      promoter activity through two distinct mechanisms. Moreover, the GATA competitors
      described here should provide invaluable in vitro and in vivo tools for the study
      of GATA- dependent transcription and the identification of new target genes.

PMID- 11518813
TI  - Wrapping up DiGeorge syndrome in a T-box?

PMID- 11518814
TI  - Yeast-worm-animal similarities in insulin-like receptors and signal transduction:
      the aging pathway goes through insulin signaling.

PMID- 11518815
TI  - The developing bone: slave or master of its cells and molecules?
AB  - A large number of molecular, cellular, and epidemiologic factors have been
      implicated in the regulation of bone development. A major unsolved problem is how
      to integrate these disparate findings into a concept that explains the
      development of bone as an organ. Often events on the organ level are simply
      presented as the cumulative effect of all factors that individually are known to
      influence bone development. In such a cumulative model it must be assumed that
      each bone cell carries the construction plan of the entire skeletal anatomy in
      its genes. This scenario is implausible, because it would require an astronomical
      amount of positional information. We therefore propose a functional model of bone
      development, which is based on Frost's mechanostat theory. In this model the
      genome only provides positional information for the basic outline of the skeleton
      as a cartilaginous template. Thereafter, bone cell action is coordinated by the
      mechanical requirements of the bone. When mechanical challenges exceed an
      acceptable level (the mechanostat set point), bone tissue is added at the
      location where it is mechanically necessary. The main mechanical challenges
      during growth result from increases in bone length and in muscle force. Hormones,
      nutrition, and environmental factors exert an effect on bone either directly by
      modifying the mechanostat system or indirectly by influencing longitudinal bone
      growth or muscle force. Predictions based on this model are in accordance with
      observations on prenatal, early postnatal, and pubertal bone development. We
      propose that future studies on bone development should address topics that can be
      derived from the mechanostat model.

PMID- 11518816
TI  - Toll-like receptors as sensors of pathogens.
AB  - Initial recognition of microbes, as they enter the body, is based on germ line
      encoded pattern recognition receptors that selectively bind to essential
      components of pathogens. This allows the body to respond immediately to the
      microbial invasion before the development of active immunity. The signal
      transducing receptors that trigger the acute inflammatory cascade have been
      elusive until very recently. On the basis of their genetic similarity to the Toll
      signaling pathway in Drosophila, mammalian Toll-like receptors (TLRs) have been
      identified. By now, nine transmembrane proteins in the TLR family have been
      described. Mammalian TLR4 is the signal-transducing receptor activated by the
      bacterial lipopolysaccharide. The activation of TLR4 leads to DNA binding of the
      transcription factor NF-kappaB, resulting in activation of the inflammatory
      cascade. Activation of other TLRs is likely to have similar consequences. TLR2
      mediates the host response to Gram-positive bacteria and yeast. TLR1 and TLR6 may
      participate in the activation of macrophages by Gram-positive bacteria, whereas
      TLR9 appears to respond to a specific sequence of bacterial DNA. The TLRs that
      control the onset of an acute inflammatory response are critical antecedents for
      the development of adaptive acquired immunity. Genetic and developmental
      variation in the expression of microbial pattern recognition receptors may affect
      the individual's predisposition to infections in childhood and may contribute to
      susceptibility to severe neonatal inflammatory diseases, allergies, and
      autoimmune diseases.

PMID- 11518817
TI  - Persistent organic pollutants in children.

PMID- 11518818
TI  - Cerebral hemodynamic response to unpleasant odors in the preterm newborn measured
      by near-infrared spectroscopy.
AB  - Newborn infants in intensive care units are exposed to several unfamiliar smells,
      mostly related to the nosocomial environment. How the preterm baby perceives
      these olfactory stimulations remains unclear. Near-infrared spectroscopy can be
      performed noninvasively above the olfactory cortex to monitor changes of cerebral
      blood flow as an indicator of cortical activation. The aim of this study was to
      explore by near-infrared spectroscopy how odorous substances routinely used in
      the neonatal intensive care unit influence bilateral cortical hemodynamics in the
      olfactory region of the brains of preterm infants. Specifically, a detergent
      (Neomidil) and an adhesive remover (Remove) have been tested. Twenty preterm
      neonates of gestational age 30-37 wk (mean 33.7 +/- 2.3 SD) and postconceptional
      age 32-37.3 wk (mean 35.5 +/- 2.75 SD) were monitored by near-infrared
      spectroscopy. Two optode pairs were placed above the anterior orbitofrontal gyri,
      which is involved in olfactory processing, on each side of the skull. Fifteen
      babies were exposed to the smell of a disinfectant and five babies to that of a
      detergent, both applied to small cotton pads. Changes of oxygenated Hb and
      deoxygenated Hb were recorded before, during, and after a 10-s stimulus. In 17
      out of 20 babies, there was a decrease in oxygenated Hb and total Hb after the
      exposure to the substances. The decrease was significantly greater in the right
      side than in the left side. This change was different from that observed in our
      previous study after exposure to colostrum and the pleasant smell of vanilla,
      which elicited an increase in blood oxygenation in the same region. The biologic
      significance of this finding is unknown. We conclude that cortical hemodynamic
      modifications occur in the preterm newborn after exposure to preparations
      commonly used in the neonatal intensive care unit. A lateralization seems to
      occur in processing unpleasant olfactory cues.

PMID- 11518819
TI  - Early childhood determinants of organochlorine concentrations in school-aged
      children.
AB  - We investigated whether early childhood factors such as breast-feeding, parity,
      and smoking contribute to the variation of organochlorine compounds (OC:
      dichlorodiphenyldichloroethene, hexachlorobenzene, beta-hexachlorocyclohexane,
      and the sum of polychlorinated biphenyls including the congeners 101, 118, 138,
      153, 170, 180, 183, and 187) at approximately 7 y of age. OC were measured in
      whole blood of 350 children. Pregnancy characteristics and the child's living
      conditions were gathered by questionnaires administered to the parents and
      interviews with the mother. Height and weight were determined during the medical
      examination. Exclusion of incomplete data and nonbiologic children of the mothers
      yielded a sample of 337 children. We applied regression analysis with indicator
      variables, controlling for confounders. No systematic association was detected
      for birth order or maternal smoking during pregnancy. The OC concentrations are
      diluted in children with a higher body mass index (>18 kg/m(2)). We found a
      strong, dose-dependent relationship between the duration of breast-feeding (none,
      1-4 wk, 5-8 wk, 9-12 wk, >12 wk) and the concentration of all five OCs. Of the
      potential determinants analyzed, more of the variance of the OC concentration is
      accounted for by breast-feeding than by any other variable. Exclusive breast
      feeding beyond 12 wk was associated with a doubling of OC whole blood
      concentration compared with bottle-fed children (dichlorodiphenyldichloroethene,
      0.28 microg/L versus 0.55 microg/L; beta-hexachlorocyclohexane, 0.05 microg/L
      versus 0.14 microg/L; hexachlorobenzene, 0.14 microg/L versus 0.25 microg/L; sum
      of polychlorinated biphenyls, 0.25 microg/L versus 0.55 microg/L). These findings
      indicate that breast-feeding can lead to an extended duration of increased OC
      exposure in childhood.

PMID- 11518820
TI  - A novel WT1 gene mutation associated with wilms' tumor and congenital male
      genitourinary malformation.
AB  - WT1 is located on the short arm of human chromosome 11 and consists of 10 coding
      exons. Mutations of this gene have been reported to be the cause of Wilms' tumor,
      congenital male genitourinary malformations, and/or renal disorders. We describe
      here a novel WT1 gene mutation, i.e. a point mutation at intron 7 (+2) in both
      the tumor and the germline cells of a patient with Wilms' tumor and congenital
      male genitourinary malformation, but without renal disorder. The position of the
      mutation is at a splice donor site of intron 7, which causes the splicing out of
      exon 7 and generates a truncated protein. This type of mutation in the WT1 zinc
      finger domain has not been reported before. The mutation is of paternal origin
      and is heterozygous in the germline cells. In the tumor cells, however, the
      maternal allele is largely lost, from 11p12 to 11p15, which results in maternal
      loss of heterozygosity. These results, together with the data from previous
      reports, suggest that WT1 may function in gonadogenesis, nephrogenesis, and
      Wilms' tumor tumorigenesis.

PMID- 11518821
TI  - The varicella-autoantibody syndrome.
AB  - This cross-sectional study was conducted to determine the incidence of
      autoantibodies to phospholipids and coagulation proteins in children with acute
      varicella zoster virus (VZV) infection. Study groups included children with VZV
      alone or complicated by purpura fulminans and/or thromboembolism. VZV naive
      children and children who had VZV >1 y before sample collection formed a control
      group. Blood was assayed for the following: free protein S (PS), protein C,
      antithrombin, and prothrombin; antibody binding to these proteins; lupus
      anticoagulant; anticardiolipin antibody; antiphospholipid antibodies; and
      prothrombin fragment 1+2. Data regarding coinfections was collected. Forty-three
      VZV-infected children showed an increased frequency of lupus anticoagulant,
      anticardiolipin antibody, antiphospholipid antibodies, and autoantibodies to PS,
      protein C, prothrombin, and antithrombin in comparison to 52 children without
      acute VZV (p < 0.0001). Seventeen children with VZV and purpura fulminans and/or
      thromboembolism showed a statistically significant decrease in free PS,
      significantly increased PS IgG antibody, and significantly increased prothrombin
      fragment 1+2 (p < 0.0001) compared with the group without acute VZV and the group
      with uncomplicated VZV. Twenty-six children with uncomplicated VZV showed
      increased PS IgG antibody (p < 0.001) compared with the children without acute
      VZV. For all groups combined, elevated PS IgG antibody showed negative
      correlation with free PS (p < 0.0001) and positive correlation with prothrombin
      fragment 1+2 (p = 0.0002). Autoantibodies were transient. Transient
      antiphospholipid and coagulation protein autoantibodies were common with VZV
      infection, but were not predictive of thrombotic complications.

PMID- 11518822
TI  - Hyperinsulinism and hyperammonemia syndrome: report of twelve unrelated patients.
AB  - Hyperinsulinism and hyperammonemia syndrome has been reported as a cause of
      moderately severe hyperinsulinism with diffuse involvement of the pancreas. The
      disorder is caused by gain of function mutations in the GLUD1 gene, resulting in
      a decreased inhibitory effect of guanosine triphosphate on the glutamate
      dehydrogenase (GDH) enzyme. Twelve unrelated patients (six males, six females)
      with hyperinsulinism and hyperammonemia syndrome have been investigated. The
      phenotypes were clinically heterogeneous, with neonatal and infancy-onset
      hypoglycemia and variable responsiveness to medical (diazoxide) and dietary
      (leucine-restricted diet) treatment. Hyperammonemia (90-200 micromol/L, normal
      <50 micromol/L) was constant and not influenced by oral protein, by protein- and
      leucine-restricted diet, or by sodium benzoate or N-carbamylglutamate
      administration. The patients had mean basal GDH activity (18.3 +/- 0.9
      nmol/min/mg protein) not different from controls (17.9 +/- 1.8 nmol/min/mg
      protein) in cultured lymphoblasts. The sensitivity of GDH activity to inhibition
      by guanosine triphosphate was reduced in all patient lymphoblast cultures
      (IC(50), or concentrations required for 50% inhibition of GDH activity, ranging
      from 140 to 580 nM, compared with control IC(50) value of 83 +/- 1.0 nmol/L). The
      allosteric effect of ADP was within the normal range. The activating effect of
      leucine on GDH activity varied among the patients, with a significant decrease of
      sensitivity that was correlated with the negative clinical response to a leucine
      restricted diet in plasma glucose levels in four patients. Molecular studies were
      performed in 11 patients. Heterozygous mutations were localized in the antenna
      region (four patients in exon 11, two patients in exon 12) as well as in the
      guanosine triphosphate binding site (two patients in exon 6, two patients in exon
      7) of the GLUD1 gene. No mutation has been found in one patient after sequencing
      the exons 5-13 of the gene.

PMID- 11518823
TI  - 3,3'-Diiodothyronine sulfate excretion in maternal urine reflects fetal thyroid
      function in sheep.
AB  - We have shown that there is significant fetal-to-maternal transfer of sulfated
      metabolites of thyroid hormone after fetal infusion of a pharmacologic amount of
      3,3',5-triiodothyronine (T(3)) or sulfated T(3) in late pregnancy in sheep (Am J
      Physiol 277:E915, 1999). The transferred iodothyronine sulfoconjugate, i.e. 3,3'
      diiodothyronine sulfate (T(2)S), of fetal origin appears in maternal sheep urine.
      The present study was carried out to assess the contribution of T(2)S of fetal
      origin to the urinary pool in ewes. Eighteen date-bred ewes (mean gestational age
      of 115 d) and their twin fetuses were divided into four groups. In group I
      (control, n = 5), both ewes (M) and their fetuses (F) were sham operated for
      thyroidectomy (Tx). In group II, the ewes (MTx, n = 4) and, in group III, the
      fetuses (FTx, n = 4) were subjected to Tx. In group IV (MTx.FTx, n = 5), both the
      ewe and fetus had Tx. After 10-12 d, fetal and/or maternal hypothyroidism were
      confirmed by serum thyroxine (<15 nmol/L) measurements. In addition, we infused
      radioactive T(3) without disturbing the T(3) pool in three singleton near-term
      fetuses and assessed the amount of radioactive iodothyronine that appeared in
      maternal urine (MU). After infusing [(125)I-3'],3,5-T(3) via fetal vein to the
      near-term normal fetuses, radioactive T(2)S was identified as the major
      metabolite in MU by HPLC and T(2)S-specific antibody. MU T(2)S excretion
      (pmol/mmol creatinine) was significantly reduced by FTx and MTx.FTx but not by
      MTx. In addition, positive correlations (p < 0.01) were found between MU T(2)S
      excretion and fetal serum thyroxine and T(3) concentrations but not with maternal
      serum thyroxine or T(3) levels. T(2)S of fetal origin contributes significantly
      to the MU pool.

PMID- 11518824
TI  - Combined prostaglandin and nitric oxide inhibition produces anatomic remodeling
      and closure of the ductus arteriosus in the premature newborn baboon.
AB  - After birth, the full-term ductus arteriosus actively constricts and undergoes
      extensive histologic changes that prevent subsequent reopening. These changes are
      thought to occur only if a region of intense hypoxia develops within the ductus
      wall after the initial active constriction. In preterm infants, indomethacin
      induced constriction of the ductus is often transient and is followed by
      reopening. Prostaglandins and nitric oxide both play a role in inhibiting ductus
      closure in vitro. We hypothesized that combined inhibition of both prostaglandin
      and nitric oxide production (with indomethacin and N-nitro-L-arginine (L-NA),
      respectively) may be required to produce the degree of functional closure that is
      needed to cause intense hypoxia. We used preterm (0.67 gestation) newborn baboons
      that were mechanically ventilated for 6 d: 6 received indomethacin alone, 7
      received indomethacin plus L-NA, and 16 received no treatment (control). Just
      before necropsy, only 25% of control ductus and 33% of indomethacin-treated
      ductus were closed on Doppler examination; in contrast, 100% of the indomethacin
      plus-L-NA-treated ductus were closed. Control and indomethacin-treated baboons
      developed negligible-to-mild ductus hypoxia (EF5 technique). Similarly, there was
      minimal evidence of ductus remodeling. In contrast, indomethacin-plus-L-NA
      treated baboons developed intense hypoxia in regions where the ductus was most
      constricted. The hypoxic muscle strongly expressed vascular endothelial growth
      factor, and proliferating luminal endothelial cells filled and occluded the
      lumen. In addition, cells in the most hypoxic regions were undergoing DNA
      fragmentation. In conclusion, preterm newborns are capable of remodeling their
      ductus, just like the full-term newborn, if they can reduce their luminal blood
      flow to a point that produces intense ductus wall hypoxia. Combined prostaglandin
      and nitric oxide inhibition may be necessary to produce permanent closure of the
      ductus and prevent reopening in preterm infants.

PMID- 11518825
TI  - TBC3711, an ET(A) receptor antagonist, reduces neonatal hypoxia-induced pulmonary
      hypertension in piglets.
AB  - The pulmonary vasculature of newborns with persistent pulmonary hypertension is
      characterized by active vasoconstriction and vascular remodeling. It has been
      suggested that endothelin-1 (ET-1), a potent vasoconstrictor and growth promoter,
      may be involved in the pathogenesis of persistent pulmonary hypertension of the
      newborn. To determine whether treatment with an ET(A) receptor antagonist can
      reverse pulmonary hypertension in the neonate, 1-d-old piglets were exposed to
      hypoxia for 3 d to induce pulmonary hypertension and then treated for the
      remainder of the 14 d with an orally active, nonpeptidic ET(A) antagonist
      (TBC3711, 22 mg x kg(-1) x d(-1)). At the end of the exposure, Hb, pulmonary
      artery pressure, right ventricle to left ventricle plus septum weight ratio,
      percentage wall thickness, ET-1 circulating levels, perfusion pressure, and
      dilator response to the nitric oxide (NO) donor, SIN-1 (3-morpholinosydnonimine-N
      ethylcarbamide) in isolated perfused lungs were determined. Exhaled NO and
      hemodynamic variables were also examined in an intact anesthetized animal
      preparation that had undergone the same treatment. By 3 d of exposure to hypoxia,
      piglets had already developed significant pulmonary hypertension as estimated by
      their pulmonary artery pressure (24.0 +/- 1.3 mm Hg versus 14.2 +/- 3.4 mm Hg)
      and percentage wall thickness (26.6 +/- 5.9% versus 18.7 +/- 2.4% for vessels 0
      30 microm). Whereas further exposure to hypoxia for 14 d did not enhance the
      increase in pulmonary artery pressure and percentage wall thickness, it did
      augment the right ventricle to left ventricle plus septum weight ratio (0.71 +/-
      0.09 versus 0.35 +/- 0.01). ET-1 circulating levels were increased only when
      exposure to hypoxia was prolonged to 14 d (5.1 +/- 2.4 pg/mL versus 1.0 +/- 0.4
      pg/mL). Treatment with TBC3711 from d 3 to d 14, once pulmonary hypertensive
      changes were established and while hypoxic exposure persisted, caused significant
      reduction in the right ventricle to left ventricle plus septum weight ratio (0.60
      +/- 0.06), pulmonary artery pressure (20.0 +/- 4.8 mm Hg), and percentage wall
      thickness (18.5 +/- 3.3%) and restored the dilator response to the NO donor SIN
      1. Prolonged hypoxia markedly reduced exhaled NO concentrations (0.3 +/- 0.6
      ppb), although treatment of hypoxic animals with TBC3711 restored the
      concentration of exhaled NO (4.4 +/- 2.8 ppb) to the level of normoxic controls
      (4.9 +/- 3.0 ppb). Lastly, treatment with TBC3711 increased ET-1 circulating
      levels in both the normoxic (5.4 +/- 2.8 pg/mL) and hypoxic (13.0 +/- 6.3 pg/mL)
      groups. In conclusion, the specific ET(A) receptor antagonist, TBC3711, can
      significantly ameliorate the morphologic changes encountered in hypoxia-induced
      pulmonary hypertension in the newborn piglet and may improve the dilator response
      to NO.

PMID- 11518826
TI  - Delivery of salbutamol pressurized metered-dose inhaler administered via small
      volume spacer devices in intubated, spontaneously breathing rabbits.
AB  - Little is known about the ability of small-volume valved spacer devices to
      deliver a significant amount of an aerosolized drug to the lungs of babies. This
      study compared the in vitro delivery of salbutamol administered via Aerochamber
      Infant (145 mL), Babyhaler (350 mL), and metallic NES-spacer (250 mL), as well as
      the in vivo delivery using an animal model. The lung deposition study of
      technetium-99m-labeled salbutamol was conducted in six anesthetized, intubated
      (3.0-mm endotracheal tube simulating oropharyngeal deposition), spontaneously
      breathing New Zealand White rabbits, a model for 3-kg babies. Each rabbit was
      studied on three separate occasions, once with each spacer device. The amount of
      radioactivity deposited in the spacer device, the endotracheal tube, the lungs,
      or the body was measured by a gamma camera and expressed as a percentage of the
      emitted labeled dose. The emitted dose and particle size distribution of
      salbutamol via the three spacer devices were measured using unit dose sampling
      tubes and an eight-stage Anderson cascade impactor, respectively. The results
      were compared by ANOVA or Student-Newman-Keuls test when indicated. In vitro, the
      NES-spacer and Babyhaler were equivalent for delivering particles <5.8 microm in
      diameter (NES-spacer = Babyhaler > Aerochamber-Infant; p < 0.05). In vivo, the
      lung and body deposition was low with all spacer devices (range: 0.52-5.40% of
      the delivered dose) but greater with the NES-spacer than with the Aerochamber
      Infant or the Babyhaler (5.40 +/- 2.40%, 2.91 +/- 0.86%, 0.52 +/- 0.46%,
      respectively; p = 0.002). These results suggest the metal-valved spacer device
      may be preferable for delivering pressurized aerosols to spontaneously breathing
      infants.

PMID- 11518827
TI  - Effects of quality of energy intake on growth and metabolic response of enterally
      fed low-birth-weight infants.
AB  - Carbohydrate and fat may vary in their ability to support protein accretion and
      growth. If so, variations in the source of nonprotein energy might be used to
      therapeutic advantage in enterally fed low-birth-weight infants. To test the
      hypothesis that high-carbohydrate diets are more effective than isocaloric high
      fat diets in promoting growth and protein accretion, low-birth-weight infants
      weighing 750-1600 g at birth were randomized in a double blind study to receive
      one of five formulas differing only in the quantity and quality of nonprotein
      energy. Groups 1, 2, and control received 130 kcal x kg(-1) x d(-1) with 35, 65,
      and 50% of the nonprotein energy as carbohydrate. Groups 3 and 4 received energy
      intake of 155 kcal x kg(-1) x d(-1) with 35 and 65% of the nonprotein energy as
      carbohydrate. Protein intake of all groups was 4 g x kg(-1) x d(-1). Growth and
      metabolic responses were followed weekly, and macronutrient balances including 6
      h indirect calorimetry were performed biweekly. Greater rates of weight gain and
      nitrogen retention were observed at high-carbohydrate intake compared with high
      fat intake at both gross energy intakes. Greater rates of energy storage and an
      increase in skinfold thickness were observed in group 4 (high-energy high
      carbohydrate diet) despite higher rates of energy expenditure. These data support
      the hypothesis that at isocaloric intakes, carbohydrate is more effective than
      fat in enhancing growth and protein accretion in enterally fed low-birth-weight
      infants. However, a diet with high-energy and high-carbohydrate content also
      results in increased fat deposition.

PMID- 11518828
TI  - Measuring intramucosal pH in very low birth weight infants.
AB  - Maintenance of adequate perfusion is essential for health of the intestinal
      mucosa. Methods available to assess intestinal perfusion provide information on
      mesenteric blood flow, which may differ from mucosal flow. Intramucosal pH
      (pH(i)) is influenced by tissue oxygenation and perfusion. Gastric pH(i) can be
      measured using the technique of tonometry. A prospective observational clinical
      study was performed to examine relationships between measured gastric pH(i) and
      mucosal CO(2) (mCO(2)), and acid-base balance, gastrointestinal complications
      (necrotizing enterocolitis and perforation), and death in infants <1500 g birth
      weight. A nasogastric tonometry catheter (size 5F) was inserted into the stomach
      of infants, and pH(i) was calculated from mCO(2) levels measured using saline
      tonometry. Measurements were performed at 3, 12, 24, and 48 h, then daily until
      arterial access was unavailable. Two hundred eleven sets of measurements were
      performed on 38 infants [birth weight (mean +/-SD), 863 +/- 241 g; gestation,
      26.5 +/- 1.8 wk; and median Clinical Risk Index for Babies score, 8.0
      (interquartile range, 5.0-10.75)]. Mean pH(i) was 7.27 (95% confidence interval,
      7.26-7.28) and mean mCO(2) was 47.0 mm Hg (95% confidence interval, 45.7-48.3 mm
      Hg). pH(i) and mCO(2) correlated significantly with arterial pH (pH(a)), arterial
      PCO(2) (PaCO(2)), and arterial base excess. There were no significant
      relationships between pH(a) and pH gap (pH(a)-pH(i)) or CO(2) gap (mCO(2)
      PaCO(2)). Recurrent low pH(i) (<7.2 on more than one occasion) and an
      mCO(2)/PaCO(2) ratio of > or =1.29 were significantly associated with an increase
      in gastrointestinal complications. There were no statistically significant
      associations with death. In conclusion, changes in pH gap and CO(2) gap can occur
      without alteration in pH(a). Abnormalities in pH(i) might predict
      gastrointestinal complications in infants <1500 g.

PMID- 11518829
TI  - Twenty-four hours of mild hypothermia in unsedated newborn pigs starting after a
      severe global hypoxic-ischemic insult is not neuroprotective.
AB  - Three to 12 h of mild hypothermia (HT) starting after hypoxia-ischemia is
      neuroprotective in piglets that are anesthetized during HT. Newborn infants
      suffering from neonatal encephalopathy often ventilate spontaneously and are not
      necessarily sedated. We aimed to test whether mild posthypoxic HT lasting 24 h
      was neuroprotective if the animals were not sedated. Thirty-nine piglets (median
      weight 1.6 kg, range 0.8-2.2 kg; median age 24 h, range 7-48 h) were anesthetized
      and ventilated and subjected to a 45-min hypoxic (FiO(2) approximately 6%) global
      insult (n = 36) or sham hypoxia (n = 3). On reoxygenation, 18 were maintained
      normothermic (NT, 39.0 degrees C) for 72 h, and 21 were cooled from 39 (NT) to 35
      degrees C (HT) for the first 24 h before NT was resumed (18 experimental, three
      sham hypoxia). Cardiovascular parameters and intermittent EEG were documented
      throughout. The brain was perfusion fixed for neuropathology and five main areas
      examined using light microscopy. The insult severity (duration in minutes of EEG
      amplitude < 7 microV) was similar in the NT and HT groups, mean +/- SD (28 +/-
      7.2 versus 27 +/- 8.6 min), as was the mean FiO(2) (5.9 +/- 0.7 versus 5.8 +/-
      0.8%) during the insult. Six NT and seven HT piglets developed posthypoxic
      seizures that lasted 29 and 30% of the time, respectively. The distribution and
      degree of injury (0.0-4.0, normal-maximal damage) within the brain (hippocampus,
      cortex/white matter, cerebellum, basal ganglia, thalamus) were similar in the NT
      and HT groups (overall score, mean +/- SD, 2.3 +/- 1.5 versus 2.4 +/- 1.3) as was
      the EEG background amplitude at 3 h (13 +/- 3.5 versus 10 +/- 3.3 microV). The HT
      animals shivered and were more active. The sham control group (n = 3) shivered
      but had normal physiology and neuropathology. Plasma cortisol was significantly
      higher in the HT group during the HT period, 766 +/- 277 versus 244 +/- 144
      microM at 24 h. Mild postinsult HT for 24 h was not neuroprotective in unsedated
      piglets and did not reduce the number of animals that developed posthypoxic
      seizures. Cortisol reached 3 times the NT value at the end of HT. We speculate
      that the stress of shivering and feeling cold interfered with the previously
      shown neuroprotective effect of HT. Research on the appropriateness of sedation
      during clinical HT is urgent.

PMID- 11518830
TI  - Interferon-gamma and interleukin-10 production among HIV-1-infected and
      uninfected infants of HIV-1-infected mothers.
AB  - Immunologic consequences of exposure to HIV-1 in utero are still poorly
      understood. This study investigates relationships between type-1 [interferon
      gamma (IFN-gamma)] and type-2 (IL-10) cytokine production and maternal-infant HIV
      1 transmission. Cord blood leukocytes from deliveries of 71 HIV-1-infected and 11
      uninfected mothers were tested for in vitro IFN-gamma and IL-10 production after
      phytohemagglutinin (PHA) stimulation. The infants of these HIV-1-infected mothers
      were followed prospectively after birth to determine HIV vertical transmission,
      and IFN-gamma and IL-10 production was measured again at 6 mo. Median PHA
      stimulated IFN-gamma production was 210 pg/mL in cord blood cells from infected
      and 73 pg/mL from uninfected mothers (p = 0.12), and median PHA-stimulated IL-10
      production was 491 pg/mL in cord blood cells from infected and 161 pg/mL from
      uninfected mothers (p = 0.004). PHA-stimulated IFN-gamma and IL-10 production
      alone were not significantly associated with transmission, but relationships
      between the two cytokines differed among infected and uninfected infants of HIV-1
      infected mothers. PHA-stimulated IFN-gamma and IL-10 production was positively
      correlated among infected (r = 0.7, p = 0.12 in cord blood and r = 0.66, p = 0.03
      at 6 mo) but not uninfected infants, and stronger relative production of IFN
      gamma to IL-10 was observed among exposed uninfected than among infected infants
      (p = 0.04). Exposure in utero to HIV-1 may augment production of IL-10 detectable
      in fetal cord blood. Stronger relative production of IFN-gamma to IL-10 in cord
      blood cells from infants of HIV-1-infected mothers may be associated with
      protection against perinatal HIV infection.

PMID- 11518831
TI  - Bone mineral density assessed by phalangeal radiographic absorptiometry before
      and during long-term growth hormone treatment in girls with Turner's syndrome
      participating in a randomized dose-response study.
AB  - To assess bone mineral density (BMD) in girls with Turner's syndrome before and
      during long-term treatment with GH, longitudinal measurements using phalangeal
      radiographic absorptiometry were performed in 68 girls with Turner's syndrome.
      These previously untreated girls, age 2-11 y, participating in a randomized, dose
      response trial, were randomly assigned to one of three GH dosage groups: group A,
      4 IU/m(2)/d ( approximately 0.045 mg/kg/d); group B, first year 4 IU/m(2)/d,
      thereafter 6 IU/m(2)/d ( approximately 0.0675 mg/kg/d); or group C, first year 4
      IU/m(2)/d, second year 6 IU/m(2)/d, thereafter 8 IU/m(2)/d ( approximately 0.090
      mg/kg/d). In the first 4 y of GH treatment, no estrogens for pubertal induction
      were prescribed to the girls. Thereafter, girls started with 17beta-estradiol (5
      microg/kg body weight/d, orally) when they had reached the age of 12 y. BMD
      results were adjusted for bone age and sex, and expressed as SD scores using
      reference values of healthy Dutch girls. At baseline, almost every individual BMD
      value of bone consisting predominantly of cortical bone, as well as that of bone
      consisting predominantly of trabecular bone, was within the normal range of
      healthy girls and the SD scores were not significantly different from zero [mean
      (SE) 0.38 (0.22) and -0.04 (0.13)]. During 7 y of GH treatment, BMD SD scores
      showed a significant increase to values significantly higher than zero [mean (SE)
      0.87 (0.15) and 0.95 (0.14)]. The increment in BMD SD score of bone consisting
      predominantly of cortical bone was significantly higher in group C compared with
      that of the other two GH dosage groups. The pretreatment bone age was
      significantly negatively related to the increment in BMD SD score. We found no
      significant influence of spontaneous puberty or the use of low-dose estrogens in
      the last 3 y of the study period on the increment in BMD SD score during 7 y of
      GH treatment. In conclusion, most untreated young girls with Turner's syndrome
      have a normal volumetric BMD. During 7 y of GH treatment with 4, 6, or 8
      IU/m(2)/d, the BMD SD score increased significantly.

PMID- 11518832
TI  - Newborn piglets with meconium aspiration resuscitated with room air or 100%
      oxygen.
AB  - We investigated whether newborn piglets exposed to hypoxemia and severe meconium
      aspiration could be reoxygenated with room air as efficiently as with 100% O(2).
      Twenty-one 2- to 5-d-old piglets were randomly divided into three groups: 1) the
      room air group: hypoxemia, meconium aspiration, and reoxygenation with room air
      (n = 8); 2) the O(2) group: hypoxemia, meconium aspiration, and reoxygenation
      with 100% O(2) (n = 8); and 3) the control group: meconium aspiration, and
      reoxygenation with room air (n = 5). Hypoxemia was induced by ventilation with 8%
      O(2) until the mean blood pressure reached <20 mm Hg or the base excess reached <
      20 mM. At this point, reoxygenation was started with either room air or 100%
      O(2). Three milliliters per kilogram of meconium 110 mg/mL was instilled into the
      trachea immediately before the start of reoxygenation. The O(2) tension in
      arterial blood was significantly lower in the room air group; at 5 min of
      reoxygenation it was 9.1 +/- 0.5 kPa versus 43.5 +/- 6 kPa in the O(2) group (p <
      0.05). At 5 min of reoxygenation the tidal volume per kilogram was 12.1 +/- 0.7
      mL/kg in the room air group and 13.1 +/- 0.9 mL/kg in the O(2) group (NS). There
      were no significant differences between the room air and the O(2) groups during
      120 min of reoxygenation in mean arterial blood pressure, pulmonary arterial
      pressure, cardiac index, base excess, or plasma hypoxanthine. In conclusion,
      hypoxic newborn piglets with meconium aspiration were found to be reoxygenated as
      efficiently with room air as with 100% O(2).

PMID- 11518833
TI  - Relationships between 24 h blood pressure load and target organ damage in
      patients with mild-to-moderate essential hypertension.
AB  - OBJECTIVE: To analyse the relationships between 24 h blood pressure load (the
      percentage of systolic/diastolic blood pressures exceeding 140/90 mmHg while
      awake and 120/80 mmHg during sleep) and some indices of hypertensive target organ
      involvement, independently of the mean level of 24 h blood pressure. METHODS: One
      hundred and thirty patients with mild-to-moderate hypertension underwent 24 h
      ambulatory blood pressure monitoring, ocular fundus examination, microalbuminuria
      assay and two-dimensional guided M-mode echocardiography. The study population
      was divided into subsets according to the systolic and diastolic 24 h blood
      pressure load values predicted from the regression equation relating 24 h blood
      pressure load to 24 h mean blood pressure. The subjects with an observed load
      above this predicted value were included in the higher blood pressure load
      groups, the remaining ones being included in the lower groups. RESULTS: Relative
      myocardial wall thickness and total peripheral resistance were greater, and mid
      wall fractional shortening, end-systolic stress-corrected mid-wall fractional
      shortening and cardiac index lower, in the subjects with a higher systolic blood
      pressure load. Moreover, the stroke index:pulse pressure ratio was reduced, and a
      greater prevalence of hypertensive retinopathy was observed in the higher
      systolic load group. On the contrary, no statistically significant difference was
      found for any of the cardiac, renal and funduscopic parameters examined when the
      two groups with a higher and lower 24 h diastolic blood pressure load were
      compared. CONCLUSIONS: Our results seem to suggest that, in mild-to-moderate
      arterial hypertension, a high 24 h systolic blood pressure load may be
      associated, independently of the average level of 24 h systolic ambulatory blood
      pressure, with an adverse cardiovascular risk profile.

PMID- 11518834
TI  - No impact of blood pressure variability on microalbuminuria and left ventricular
      geometry: analysis of daytime variation, diurnal variation and 'white coat'
      effect.
AB  - OBJECTIVE: To investigate the influence of blood pressure variability on target
      organ involvement. METHODS: Using a cross-sectional study of a hypertension
      clinic at a district general hospital, 420 patients with newly diagnosed
      untreated essential hypertension referred on a consecutive basis from general
      practice and 146 normal subjects drawn at random from the Danish National
      Register underwent a variety of measurements which included: echocardiography
      with determination of left ventricular mass index and relative wall thickness and
      early morning urine albumin/creatinine ratio. Mean, standard deviation and
      coefficient of variation of automated clinic values; daytime, night-time and full
      24-h period were extracted from 24-h ambulatory blood pressure (ABP) monitoring.
      'White coat' effect and dip were calculated. Hypertensives were classified into
      subjects with high or low variability, into 'white coat' hypertensives or
      established hypertensives and into dippers or non-dippers. RESULTS: Standard
      deviation of daytime blood pressure (BP) was positively associated with target
      organ damage and BP level, which was not the case when variability was expressed
      as a coefficient of variation. Patients with high variability exhibited no more
      significant target organ damage than patients with low variability, but patients
      with established hypertension had significantly more target organ damage than the
      'white coat' hypertensives. The 'white coat' effect as such was not associated
      with increased target organ involvement. Non-dippers had significantly more
      cardiac target organ damage than dippers, but the difference disappeared after
      correction for different 24-h BP level. CONCLUSION: BP variability data obtained
      by non-invasive ABP monitoring does not seem to improve the information inherent
      in the BP level.

PMID- 11518835
TI  - Self-measurement of blood pressure: accuracy, patient preparation for readings,
      technique and equipment.
AB  - OBJECTIVE: Self-measurement of blood pressure is commonly performed by those
      persons with hypertension and is advocated in many national hypertension
      guidelines. We examined accuracy of readings, patient knowledge, and preparation
      for readings, technique and equipment. DESIGN: The study was a prospective
      observational design. Sixty-nine hypertensive patients were recruited from a
      tertiary referral center and by newspaper advertisement. All patients had
      previously self-measured their blood pressure. The patients initially measured
      their blood pressure under direct supervision in a clinic using their usual
      preparation, technique and their own equipment. Then after a five-min rest, blood
      pressures were measured twice both by research nurse and the patient in an
      alternating sequence. The nurse used a standardized blood pressure measurement
      technique. RESULTS: Inadequate patient knowledge and performance of measurement
      technique and inaccurate equipment was common. The average initial patient
      systolic reading prior to the five-minute rest was higher than that of the
      trained nurse (9.1 +/- 13 mmHg systolic, p < 0.001 and 1.5 +/- 8.0 mmHg
      diastolic, p = 0.12). Almost half (42%) of the initial patient blood pressure
      readings differed in classification of hypertension/normotension from the nurse.
      The difference between the patient and nurse readings after the five-min rest was
      3.8 +/- 11.8 / 1.1 +/- 6.8 mmHg. CONCLUSIONS: Care must be taken in interpreting
      patient self-measured blood pressure unless there has been adequate training and
      assessment of patient and equipment accuracy. Studies of health care
      professionals reveal similar problems therefore widespread efforts to standardize
      blood pressure measurement are necessary.

PMID- 11518836
TI  - Management of hypertension in the elderly using home blood pressures.
AB  - OBJECTIVE: To evaluate whether patient-measured home blood pressures alone can be
      used to manage hypertension in adults 65 years and older. METHODS: 40
      hypertensive men and women, average age 73 +/- 6 years, were randomly assigned to
      one of two treatment decision groups. The 'home' group (N = 20) had blood
      pressure managed and medication changed according to measurements taken by the
      patient at home with the Omron HEM-702 semi-automatic oscillometric digital blood
      pressure monitor and the 'clinic' group (N = 20) had medication adjusted based
      upon readings taken by the project nurse in the clinic. In both groups, treated
      hypertensives had medications adjusted downward, while untreated hypertensives
      were started on a diuretic and/or ACE inhibitor and adjustments were made upward.
      To assess the efficacy of the home measurements as a means of hypertension
      management, 24-hour ambulatory blood pressure averages, quality of life (From the
      QOL SF-36), and dosage of antihypertensive medications were compared between the
      home and clinic groups over a three-month period. RESULTS: At baseline, the
      'home' group had slightly higher ambulatory awake and sleep blood pressure than
      the 'clinic' group. At 3 months, the average awake and sleep ambulatory blood
      pressure for the 'home' group decreased to the level of the 'clinic' group.
      Values of the 'clinic' group did not change. In both groups, pressures of
      previously treated patients increased over the 3 months, while those that were
      previously untreated declined. However, this difference, to some extent, might be
      expected because the acceptable limit of pressure control (150 / 90 mmHg) was
      higher than many of the patients on medications; thus, their pressures could
      increase and still be considered controlled. Those patients who were previously
      untreated had their pressures decreased only to this level. The nurse-measured
      clinic blood pressures for the 'home' group began higher than that of the
      'clinic' group and remained higher at the end of the study. Average home
      pressures of the 'home' group were consistently lower than nurse-measured clinic
      pressures over the 3-month study period, indicating a persistent 'white coat'
      effect. Both groups had similar changes in total quality of life scores.
      Decrease/discontinuance of antihypertensive medication was also achieved equally
      in both groups at the end of 3 months. CONCLUSION: Home blood pressure monitoring
      alone may be as useful as clinic measurements for making treatment decisions in
      the elderly.

PMID- 11518837
TI  - Rapid oscillometric blood pressure measurement compared to conventional
      oscillometric measurement.
AB  - BACKGROUND: There have been few reports studying the necessary interval between
      blood pressure measurements, after the initial rest period. METHODS: Blood
      pressure was measured in 50 patients using the conventional oscillometric
      technique (COT) and the rapid oscillometric technique (ROT). RESULTS: The
      difference between COT and ROT was -1.1 / -0.1 mmHg, which was not significantly
      different (p = 0.8 / 1.0) and the pulse difference was -0.8 beats per minute (p =
      0.8). CONCLUSIONS: It is concluded that a 15-second interval between blood
      pressure readings is as accurate as a one-minute interval providing that these
      measurements are started after a 5-minute rest period.

PMID- 11518838
TI  - Assessment of sequential same arm agreement of blood pressure measurements by a
      CVProfilor DO-2020 versus a Baumanometer mercury sphygmomanometer.
AB  - OBJECTIVE: The aim of this study was to assess the accuracy of sequential same
      arm blood pressure measurement by the mercury sphygmomanometer with the
      oscillometric blood pressure measurements from a device that also determines
      arterial elasticity. METHODS: A prospective, multicentre, clinical study
      evaluated sequential same arm blood pressure measurements, using a mercury
      sphygmomanometer (Baumanometer, W. A. Baum Co., Inc., Copiague, New York, USA)
      and an oscillometric non-invasive device that calculates arterial elasticity
      (CVProfilor DO-2020 Cardiovascular Profiling System, Hypertension Diagnostics,
      Inc., Eagan, Minnesota, USA). Blood pressure was measured supine in triplicate, 3
      min apart in a randomized sequence after a period of rest. RESULTS: The study
      population of 230 normotensive and hypertensive subjects included 57% females,
      51% Caucasians, and 33% African Americans. The mean difference between test
      methods of systolic blood pressure, diastolic blood pressure, and heart rate was 
      3.2 +/- 6.9 mmHg, +0.8 +/- 5.9 mmHg, and +1.0 +/- 5.7 beats/minute. For systolic
      and diastolic blood pressure, 60.9 and 70.4% of sequential measurements by each
      method were within +/- 5 mmHg. Few or no points fell beyond the mean +/- 2
      standard deviations lines for each cuff bladder size. CONCLUSION: Sequential same
      arm measurements of the CVProfilor DO-2020 Cardiovascular Profiling System
      measures blood pressure by an oscillometric method (dynamic linear deflation)
      with reasonable agreement with a mercury sphygmomanometer.

PMID- 11518839
TI  - Comparison of the oscillometric blood pressure monitor (BPM-100(Beta) ) with the
      auscultatory mercury sphygmomanometer.
AB  - BACKGROUND: To compare directly the accuracy of the BPM-100(Beta) monitor (an
      automated oscillometric blood pressure device) with standard auscultatory mercury
      sphygmomanometry. DESIGN: The BPM-100(Beta) was connected in parallel via a T
      tube to a mercury sphygmomanometer. The BPM-100(Beta) and two trained observers
      (blinded from each other and from the BPM-100(Beta)) measured the sitting blood
      pressure simultaneously. METHODS: Means, standard deviations and ranges were
      calculated for all the demographic data: age, arm size, heart rate and blood
      pressure. The agreement between the BPM-100(Beta) and the mean of two observers
      (the reference) was determined and expressed as the mean +/- SD, as well as the
      percentage of differences falling within 5, 10 and 15 mmHg. RESULTS: Of the 92
      subjects recruited, 85 (92.4%) met the inclusion criteria, and 391 sets of
      sitting blood pressure and heart rate measurements were available for analysis.
      The mean difference between the BPM-100(Beta) monitor and the reference was -0.62
      +/- 6.96 mmHg for systolic blood pressure, -1.48 +/- 4.80 mmHg for diastolic
      blood pressure and 0.14 +/- 1.86 beats/min for heart rate. The only limitation of
      the device was its tendency to underestimate higher systolic blood pressures.
      This problem has been addressed by a minor change in the algorithm (see the
      companion publication, Blood Press Monit, 6, 161-165, 2001). CONCLUSION: The BPM
      100(Beta) is an accurate blood pressure monitor for the office setting, meeting
      all requirements of the Association for the Advancement of Medical
      Instrumentation and achieving an 'A' grade according to the British Hypertension
      Society protocol.

PMID- 11518840
TI  - Validation of a new algorithm for the BPM-100 electronic oscillometric office
      blood pressure monitor.
AB  - BACKGROUND: To test the accuracy of a new algorithm for the BPM-100, an automated
      oscillometric blood pressure (BP) monitor, using stored data from an
      independently conducted validation trial comparing the BPM-100(Beta) with a
      mercury sphygmomanometer. DESIGN: Raw pulse wave and cuff pressure data were
      stored electronically using embedded software in the BPM-100(Beta), during the
      validation trial. The 391 sets of measurements were separated objectively into
      two subsets. A subset of 136 measurements was used to develop a new algorithm to
      enhance the accuracy of the device when reading higher systolic pressures. The
      larger subset of 255 measurements (three readings for 85 subjects) was used as
      test data to validate the accuracy of the new algorithm. METHODS: Differences
      between the new algorithm BPM-100 and the reference (mean of two observers) were
      determined and expressed as the mean difference +/- SD, plus the percentage of
      measurements within 5, 10, and 15 mmHg. RESULTS: The mean difference between the
      BPM-100 and reference systolic BP was -0.16 +/- 5.13 mmHg, with 73.7% < or = 5
      mmHg, 94.9% < or = 10 mmHg and 98.8% < or = 15 mmHg. The mean difference between
      the BPM-100 and reference diastolic BP was -1.41 +/- 4.67 mmHg, with 78.4% < or =
      5 mmHg, 92.5% < or = 10 mmHg, and 99.2% < or = 15 mmHg. These data improve upon
      that of the BPM-100(Beta) and pass the AAMI standard, and 'A' grade BHS protocol.
      CONCLUSION: This study illustrates a new method for developing and testing a
      change in an algorithm for an oscillometric BP monitor utilizing collected and
      stored electronic data and demonstrates that the new algorithm meets the AAMI
      standard and BHS protocol.

PMID- 11518841
TI  - Supine and exercise systolic blood pressure predict cardiovascular death in
      middle-aged men.
AB  - AIM AND METHODS: The outcome of 1999 apparently healthy men, aged 40-59 years,
      initially investigated in the period 1972-1975, has previously been ascertained
      at 7 and 16 year follow-ups. This has now been repeated after 21 years, to
      determine whether seated systolic blood pressure (BP) during a bicycle ergometer
      exercise test adds prognostic information on cardiovascular (CV) mortality beyond
      that of systolic BP measured after 5 min of supine rest. RESULTS: After 21 years,
      41 979 years of observation, 470 patients had died, 255 from CV causes. Supine
      systolic BP [2 SD increase: relative risk (RR) 1.6, 95% confidence interval (CI)
      1.3-2.0, P < 0.0001], 6 min exercise systolic BP (2 SD increase: RR 1.6, 95% CI
      1.3-2.0, P < 0.0001) on the starting workload of 600 kpm/min (approximately 100
      W, 5880 J/min) and maximal systolic BP (2 SD increase: RR 1.5, 95% CI 1.2-1.9, P
      = 0.0005) during work were all related to CV mortality when adjusting for a large
      number of variables measured in the present study including age, exercise
      capacity, heart rates, smoking habits, glucose tolerance and serum cholesterol.
      When including other systolic BPs in the continuous multivariate analysis, supine
      systolic BP (2 SD increase: RR 1.4, 95% CI 1.04-1.9, P = 0.029) and 6 min
      systolic BP at 600 kpm/min (2 SD increase: RR 1.4, 95% CI 1.06-1.9, P = 0.017)
      were independent predictors of CV death but not maximal systolic BP during
      exercise (2 SD increase: RR 1.0, 95% CI 0.7-1.2, P = 0.95). CONCLUSION: These
      results are different from the mortality data at 16 years, when the independent
      predictive effect of supine systolic BP was cancelled out by 6 min exercise
      systolic BP at 600 kpm/min. Twenty-one years of follow-up of 1999 apparently
      healthy men disclose independently predictive information on CV death, of both
      supine systolic BP and 6 min exercise systolic BP taken at an early moderate
      workload. The influence of maximal exercise systolic BP on CV death is however
      cancelled out by the two other systolic BPs.

PMID- 11518842
TI  - Effects of three candidate genes on prevalence and incidence of hypertension in a
      Caucasian population.
AB  - BACKGROUND: The genes encoding angiotensin converting enzyme (ACE, I/D), alpha
      adducin (ADD, Gly460Trp) and aldosterone synthase (AS, -344C/T) share the
      potential of influencing blood pressure (BP) via sodium homeostasis. However,
      most studies in humans focused on single-gene effects and disregarded epistasis,
      the suppression or potentiation of a gene by other non-allelic genes. METHODS: We
      studied the singular and combined effects of the aforementioned candidate genes:
      (1) in relation to BP, plasma renin activity (PRA) and urinary aldosterone in
      1461 subjects randomly selected from a Caucasian population; and (2) in relation
      to the incidence of hypertension in a subgroup of 678 initially normotensive
      subjects followed up for 9.1 years (median). RESULTS: In cross-sectional
      analyses, AS/CC homozygosity was associated with slightly lower systolic BP (
      1.32 mmHg; P = 0.08). AS/TT homozygotes showed both lower PRA and higher urinary
      aldosterone excretion (P < or = 0.05). In multiple-gene analyses, compared with
      the whole study population, ADD/Trp subjects had a higher relative risk of
      hypertension in the presence of the AS/T allele (1.29; P = 0.05), whereas in
      combination with AS/CC homozygosity ADD/Trp subjects had the smallest relative
      risk (0.48; P = 0.003). Hypertension developed in 229 subjects (36.6 cases per
      1000 person-years). ACE/DD homozygosity, in comparison with the other ACE
      genotypes, was associated with increases in the incidence of hypertension, which
      amounted to 31% (P = 0.005) in single-gene analyses, to 59% (P = 0.004) in
      carriers of the ADD/Trp allele and to 122% (P = 0.0007) in AS/CC subjects. Among
      subjects who had both the ADD/Trp allele and the AS/CC genotype, ACE/DD
      homozygotes manifested a 252% (P = 0.001) higher incidence of hypertension.
      CONCLUSIONS: Epistatic interactions between the ACE, ADD and AS genes contribute
      to the prevalence and incidence of hypertension in Caucasians. The clinical
      relevance of the risk-conferring haplotypes identified in our prospective study
      was underscored by their positive predictive values, which under the assumption
      of a 20% life-time risk of hypertension, ranged from 29.8-40.1%.

PMID- 11518843
TI  - Blood pressure, endothelial function and circulating endothelin concentrations in
      liver transplant recipients.
AB  - OBJECTIVES: To study candidates for liver transplant before and 6 weeks after
      transplant, and to elucidate the role of endothelial dysfunction and plasma
      endothelin concentrations in the development of hypertension. DESIGN PROSPECTIVE:
      follow-up study. SETTING: Institutional, outpatient. PATIENTS: and controls
      Fifteen patients (11 men, four women, mean age 46.7+/-13.2 years) with end-stage
      liver disease (ESLD) and healthy volunteers of comparable age and sex. METHODS:
      We performed office blood pressure readings and 24 h ambulatory blood pressure
      monitoring (ABPM), measurements of endothelial-dependent vasodilatation using
      high-resolution ultrasound in the brachial artery at rest and during reactive
      hyperemia, and plasma endothelin-1 assays 3 months before and 6 weeks after the
      transplant. RESULTS: Office systolic and diastolic blood pressures increased
      significantly 6 weeks after liver transplantation (from 116.6+/-14.1 to 139.9+/
      19.5 mmHg and from 68.6+/-9.5 to 84.1+/-9.8 mmHg, respectively; both P < 0.001).
      Hypertension based on office blood pressure readings increased from 6.7 to 40% (P
      < 0.05). Mean 24 h systolic blood pressure increased from 118.7+/-10.3 to 140.0+/
      19.0 mmHg (P < 0.001), mean 24 h diastolic blood pressure increased from 86.0+/
      7.7 to 104.8+/-13.9 mmHg (P < 0.001) and heart rate increased from 74.8+/-10.2 to
      80.2+/-8.2 beats/min (P < 0.05). Brachial artery flow-mediated dilatation did not
      change throughout the study (before transplant: 4.2+/-4.0%; after transplant:
      6.3+/-5.4%; NS) and did not differ from that in controls (5.2+/-3.8%). Plasma
      endothelin-1 was increased in patients with ESLD (15.3+/-2.6 pg/ml) compared with
      controls (5.6+/-0.4 pg/ ml; P < 0.001) and remained unchanged 6 weeks after liver
      transplantation (14.1+/-3.7 pg/ml). CONCLUSION: Our results show increased blood
      pressure with suppressed circadian blood pressure variability in liver graft
      recipients 6 weeks after transplant and no change in endothelial function and
      plasma endothelin concentrations. Therefore, the blood pressure increase
      documented in our study cannot be explained by endothelial dysfunction. Twenty
      four hour ABPM should be performed routinely in patients who have undergone liver
      transplant.

PMID- 11518844
TI  - Vasorelaxant effects of the chronic treatment with melatonin on mesenteric artery
      and aorta of spontaneously hypertensive rats.
AB  - OBJECTIVE: To investigate the effect of a chronic treatment with melatonin on
      arterial pressure and a possible improvement of the vascular muscarinic and NO
      synthase (NOS) pathways in spontaneously hypertensive rats (SHR) and Wistar-Kyoto
      (WKY) rats. DESIGN AND METHODS: Mean arterial pressure (MAP), systolic (SBP),
      diastolic blood pressure (DBP), and heart rate (HR) were evaluated in conscious
      rats treated with 30 mg/kg per day of melatonin during 4 weeks. Changes in MAP
      were evaluated following an intravenous injection of the NOS inhibitor N-omega
      nitro-L-arginine methyl ester (L-NAME). Relaxant effects of acetylcholine (Ach),
      sodium nitroprusside (SNP), and the calcium ionophore A23187 were examined on
      mesenteric beds and aortic rings with or without treatment with melatonin.
      RESULTS: Melatonin produced a significant reduction of MAP, SBP, DBP and HR in
      SHR (P < 0.05). L-NAME increased the MAP of melatonin-treated SHR by the same
      magnitude as that of WKY rats which was significantly higher than that of non
      treated SHR (P< 0.05). Melatonin treatment improved the maximal relaxation of
      mesenteric arteries to A23187 in SHR (P < 0.001) to the WKY level and caused a
      slight increment in Ach- and A23187-induced vasodilations in aorta from SHR and
      WKY rats (P < 0.05). CONCLUSION: The present study showed that melatonin exerted
      a bradycardic and an antihypertensive action in SHR. The enhancement by melatonin
      of the endothelium-dependent vasodilation (Ach and/or A23187) in mesenteric
      artery and aorta from SHR and WKY rats and the higher increase in MAP following L
      NAME treatment in melatonin-treated SHR suggest the contribution of an improved
      vascular NOS pathway activity in the hypotensive effect of melatonin.

PMID- 11518845
TI  - Effect of calcium antagonist or beta blockade treatment on nitric oxide-dependent
      vasodilation and oxidative stress in essential hypertensive patients.
AB  - OBJECTIVES: Essential hypertension is associated with impaired endothelium
      dependent vasodilation caused by oxygen free radical-induced nitric oxide (NO)
      breakdown. Since calcium antagonists can improve endothelial function in
      hypertensive patients, we tested whether this beneficial effect could be related
      to restoration of NO availability by antioxidant activity. METHODS: In 10 healthy
      subjects and 20 essential hypertensive patients, we studied forearm blood flow
      (strain-gauge plethysmography) modifications induced by intrabrachial
      acetylcholine (from 0.15-15 microg/100 ml per min), bradykinin (0.005-0.05
      microg/100 ml per min), two endothelium-dependent vasodilators, and sodium
      nitroprusside (1-4 microg/100 ml forearm tissue per min), an endothelium
      independent vasodilator, in the absence and presence of NG-monomethyl-L-arginine
      (L-NMMA) (100 microg/100 ml forearm tissue per min), an NO synthase inhibitor.
      RESULTS: In controls, vasodilation to acetylcholine and bradykinin was inhibited
      by L-NMMA. In hypertensive patients, vasodilation to acetylcholine and
      bradykinin, but not to sodium nitroprusside, was blunted and resistant to L-NMMA.
      Hypertensive patients were randomized to a 12-week treatment with lacidipine (4-6
      mg/daily) or atenolol (50-100 mg/daily) (n = 10 each group). Lacidipine but not
      atenolol increased the vasodilation to acetylcholine and bradykinin and restored
      the inhibiting effect of L-NMMA on endothelium-dependent vasodilation, without
      affecting the response to sodium nitroprusside. Moreover, lacidipine reduced
      circulating markers of oxidative stress including plasma and low-density
      lipoprotein (LDL) hydroperoxides, the susceptibility of LDL to Cu2+-induced
      oxidation and the reactive oxygen species generated from human umbilical vein
      endothelial cells after incubation with LDL derived from plasma of the patients.
      CONCLUSIONS: Lacidipine increases endothelium-dependent vasodilation by restoring
      NO availability, and this effect possibly is related to antioxidant activity.

PMID- 11518846
TI  - The return of increased blood pressure after discontinuation of antihypertensive
      treatment is associated with an impaired post-ischemic skin blood flow response.
AB  - OBJECTIVE: To assess the post-ischemic skin blood flow response after withdrawal
      of antihypertensive therapy in hypertensive patients with normal blood pressure
      during treatment. DESIGN AND METHODS: Twenty hypertensive patients (group A) with
      a normal clinic blood pressure (<140/ 90 mmHg) receiving antihypertensive
      treatment (any monotherapy; one pill per day for at least 6 months) had their
      treatment discontinued. Before medication withdrawal and 2, 4, 12 and 24 weeks
      thereafter, the following measurements were made: clinic blood pressure, home
      blood pressure (three times per week, morning and evening) and skin blood flow
      response to a 5 min forearm arterial occlusion (using laser Doppler flowmetry).
      The patients were asked to perform an ambulatory blood pressure recording at any
      time if home blood pressure was > or =160/95 mmHg on two consecutive days, and
      treatment was initiated again, after determination of the skin hyperemic
      response, if daytime ambulatory blood pressure was > or =140/90 mmHg. The same
      studies were performed in 20 additional hypertensive individuals in whom
      antihypertensive treatment was not withdrawn (group B). The allocation of
      patients to groups A and B was random. RESULTS: The data fom 18 patients in group
      A who adhered strictly to the procedure were available for analysis. Seven of
      them had to start treatment again within the first 4 weeks of follow-up; four
      additional patients started treatment again during the next 8 weeks (group A1).
      The seven other patients remained untreated (group A2). The skin hyperemic
      response decreased significantly in patients in group A1 and returned to baseline
      values at the end of the study, when there were again receiving antihypertensive
      treatment. In patients in group A2 a significant attenuation of the hyperemic
      response was also observed. This impaired response was present even at the end of
      the 6 month follow-up, at which time the patients were still untreated but
      exhibited a significantly greater blood pressure than before drug
      discontinuation. The hyperemic response of patients who did not stop treatment
      (group B) did not change during the course of the study. CONCLUSIONS: Our
      findings show a decrease in the postischemic skin blood flow response after
      withdrawal of antihypertensive treatment in hypertensive patients. This impaired
      response may be due to the development of endothelial dysfunction, vascular
      remodeling, or both, and might contribute to the return of blood pressure to
      hypertensive values after withdrawal of antihypertensive therapy.

PMID- 11518848
TI  - Effect of chronic angiotensin II inhibition on the nitric oxide synthase in the
      normal rat during aging.
AB  - OBJECTIVE: To assess the effect on the cardiovascular system, of enalapril (E) or
      losartan (L) given since weaning during 6 or 18 months to normal rats. METHODS:
      Animals were divided in three groups: control (C), E-treated and L-treated;
      treated rats received 10 mg/ kg per day of drug. Systolic blood pressure (SBP),
      body weight, water and food intake (WI, FI), cardiac, left ventricular and aortic
      weight as well as the length of the tail were recorded. NADPH-diaphorase activity
      was determined as a marker of nitric oxide synthase (NOS) activity in aorta,
      arterioles of small intestine, heart and kidney of normal rats. NOS activity was
      measured as optical density (OD) in the stained tissue. Nitrate + nitrite urinary
      excretion was measured in 24 h urine. Only significant differences (P < 0.05) are
      reported. RESULTS: SBP, absolute cardiac, left ventricular and aortic weight
      increased with age. Both treatments delayed these increments. At 6 and 18 months,
      NOS activity was higher in aortic endothelium (Em) of L- and E-treated animals.
      Losartan treatment during 6 months also increased NOS activity in aortic smooth
      muscle (SM). Aortic Em NOS activity fell in the 18 months-treated and untreated
      animals. E increased NOS activity in the SM of intestinal arterioles at 6 months
      but reduced it at 18 months. CONCLUSIONS: The fact that both E and L delayed
      cardiac hypertrophy/hyperplasia and aortic growth and raised aortic endothelium
      NOS activity indicates a protective effect on cardiovascular damage due to aging,
      exerted through inhibition of angiotensin II.

PMID- 11518847
TI  - Persistent cardiovascular effects of chronic renin-angiotensin system inhibition
      following withdrawal in adult spontaneously hypertensive rats.
AB  - OBJECTIVES: It is generally accepted that short-term (4 weeks) inhibition of the
      renin-angiotensin system (RAS) of young spontaneously hypertensive rats (SHR) in
      their prehypertensive phase confers long-lasting protection from fully
      hypertensive levels in adulthood. However, there is very little data pertaining
      to the effects of such treatment in adult SHR with established hypertension.
      Therefore, we determined the relative effects of angiotensin converting enzyme
      (ACE) inhibition (perindopril), AT1 receptor blockade (candesartan cilexetil) and
      RAS-independent vasodilatation (hydralazine) and their withdrawal in adult SHR,
      on blood pressure measured by radiotelemetry, as well as on cardiac and vascular
      structure. METHODS: Adult male SHR were instrumented with radiotelemetry probes
      to measure blood pressure and heart rate continuously. SHR were given either
      vehicle, perindopril (1 mg/kg per day), candesartan cilexetil (2 mg/ kg per day)
      or hydralazine (30 mg/kg per day) at equieffective depressor doses for 4 weeks
      (treatment study). Separate groups of animals were also given identical
      treatments but were then monitored for a further 8 weeks after drug withdrawal
      (withdrawal study). An indirect in-vivo assessment of whole body vascular
      hypertrophy (mean arterial pressure during maximum vasoconstriction) was made
      during and after drug withdrawal, as was the pressor activity evoked by
      angiotensin I and angiotensin II. The effect of antihypertensive treatment on
      microalbuminuria was also assessed during and after drug withdrawal. Finally,
      left ventricular: body weight (Iv: bw) and mesenteric media: lumen ratios were
      determined either immediately after 4-week treatment (treatment study) or 8 weeks
      later (withdrawal study). RESULTS: Perindopril persistently lowered blood
      pressure in adult SHR whereas blood pressure returned to vehicle levels within
      approximately 4 and 15 days after withdrawal of hydralazine and candesartan
      cilexetil, respectively. Cardiac hypertrophy was reduced by all three treatments,
      but to a lesser extent by hydralazine (treatment study), and this regression of
      cardiac hypertrophy persisted only with both types of RAS inhibition (withdrawal
      study). Vascular hypertrophy, measured indirectly and directly, was also reduced
      by all three treatments, with perindopril and candesartan cilexetil causing
      hypotrophic and eutrophic remodelling, respectively (treatment study), although
      these changes were generally not maintained after drug withdrawal (withdrawal
      study). Angiotensin I-induced pressor responses were equally inhibited during
      treatment with either candesaran cilexetil or perindopril (and were unaffected by
      hydralazine) but normalized rapidly in both groups (within approximately 2-4
      days) after withdrawal of RAS inhibition. In addition, there was a small age
      related increase in microalbuminuria over the study period, which was not
      significantly affected by any treatment. CONCLUSIONS: Following 4-week treatment,
      candesartan cilexetil, perindopril and hydralazine caused similar
      antihypertensive effects; however, only perindopril persistently reduced blood
      pressure following drug withdrawal. Both types of RAS inhibition and hydralazine
      caused marked cardiac and vascular remodelling during treatment, whereas only the
      RAS inhibitors persistently regressed cardiac hypertrophy 8 weeks later.
      Collectively, these results indicate the importance of the RAS for the
      maintenance of hypertension and cardiovascular hypertrophy in adult SHR, as well
      as identifying differential effects of ACE inhibition and AT1 receptor blockade
      on persistent blood pressure reduction.

PMID- 11518849
TI  - Circadian blood pressure variability in adrenocorticotrophin-induced hypertension
      in the rat.
AB  - OBJECTIVES: Secondary hypertension is often characterized by loss of diurnal
      blood pressure variability. This study examined circadian (24 h) blood pressure
      variability in adrenocorticotrophin (ACTH)-induced hypertension in the Sprague
      Dawley rat. METHODS: Male Sprague-Dawley rats were randomly allocated to sham
      (0.9% saline, s.c.), n = (9), ACTH (0.5 microg/kg per day, s.c., n = 8) or ACTH
      (100 microg/kg per day, s.c., n = 7) in a room with a 12 h light/dark cycle (0600
      h to 1800 h). A radio telemetry transducer was used to measure blood pressure in
      unrestrained animals over 3 control days (C1-C3) and 10 treatment days (T1-T10).
      Heart rate, systolic (SBP), mean arterial (MAP) and diastolic (DBP) blood
      pressure were continuously recorded. Body weight was measured daily and serum
      corticosterone concentration ([B]) prior to death. RESULTS: Sham treatment had no
      effect on any parameters. ACTH 100 microg/kg per day increased SBP from 124+/-2
      pooled control (PC) to 134+/-2 mmHg (T10), MAP from 105+/-2 to 115+/-2 mmHg and
      DBP from 87+/-1 to 99+/-2 mmHg and decreased heart rate from 305+/-6 to 249+/-5
      beats/min and body weight from 299+/-6 (C3) to 280+/-8 g (T10) (all P' < 0.0036).
      Serum [B] was higher in ACTH- (881+/-44 ng/ml) than sham-treated rats (384+/-17
      ng/ml, P < 0.001). There were no differences between sham treatment and ACTH 0.5
      microg/kg per day. SBP, MAP, DBP and heart rate were consistently higher for ACTH
      100 microg/kg per day and sham-treated animals during the dark cycle (1800 h to
      0600 h) than the light cycle (0600 h to 1800 h). CONCLUSIONS: ACTH 100 microg/kg
      per day raises blood pressure in conscious unrestrained Sprague-Dawley rats
      without any change in normal diurnal rhythm.

PMID- 11518850
TI  - The spectrum of circadian blood pressure changes in type I diabetic patients.
AB  - BACKGROUND: The objective of the present study was to characterize the spectrum
      of circadian blood pressure changes in type I diabetes at different stages of
      nephropathy by using two monitorings in each patient in order to avoid intra
      individual variability. PATIENTS AND METHODS: A total of 80 type I diabetic
      subjects and the same number of age, sex and awake mean blood pressure (BP)
      matched controls were included. According to urinary albumin excretion, there
      were 57 normoalbuminurics, 15 persistent microalbuminurics and eight
      proteinurics. Two 24 h ambulatory blood pressure monitorings were performed at
      the same urinary albumin excretion stage in absence of antihypertensive treatment
      for each diabetic subject and for their respective control. Blood pressure and
      heart rate averages during 24 h, awake, sleep, and day: night ratio were
      calculated. RESULTS: Seven of the eight proteinuric subjects were hypertensives,
      whereas hypertension was absent in the normoalbuminuric and microalbuminuric
      groups. The intraindividual reproducibility in diabetics showed repeatability
      coefficients for the 24 h systolic and diastolic pressure of 33 and 42%,
      respectively. This reproducibility for the day: night ratio was generally worse,
      57% for systolic and 59% for diastolic. A progressive increment in the mean
      ambulatory BP was observed across the three groups of diabetics and the
      differences in BP observed were most evident during the night-time period. Though
      no differences in the 24 h circadian pattern were present between the
      normoalbuminurics and their controls, nocturnal differences were observed, not
      only in microalbuminurics for systolic BP (P < 0.05), but also in proteinurics
      for both systolic BP (P < 0.01) as well as diastolic BP (P < 0.05). No
      differences were observed in heart rate among the diabetic groups. The non
      dipping pattern in the two monitorings was observed in 80, 58, 18 and 10% of the
      proteinurics, microalbuminurics, normoalbuminurics and control groups,
      respectively. CONCLUSIONS: Persistent abnormal circadian variability seems to be
      an early and frequent characteristic of type I diabetics with an increased
      urinary albumin excretion. Although present in some normalbuminuric subjects, the
      frequency of this abnormality increases as the incipient nephropathy progresses.
      By the time proteinuria is established, nearly all subjects present the abnormal
      pattern.

PMID- 11518851
TI  - Effects of nebivolol and atenolol on insulin sensitivity and haemodynamics in
      hypertensive patients.
AB  - OBJECTIVES: To compare the effects of nebivolol and atenolol in 25 ambulatory
      hypertensive patients with impaired glucose tolerance. DESIGN: Clinic and
      ambulatory blood pressure, insulin sensitivity (euglycemic-hyperinsulinemic
      clamp), glucose tolerance (intravenous glucose tolerance test), systemic and
      regional haemodynamics were measured after 4 weeks of placebo and after each 16
      week treatment period in a double-blind, crossover fashion. RESULTS: Nebivolol
      and atenolol similarly reduced (P< 0.001) clinic and ambulatory blood pressure by
      approximately 15/10 mmHg, systolic and diastolic. Clinic and ambulatory heart
      rate was reduced to a greater extent (P < 0.01) by atenolol than nebivolol.
      Atenolol was associated with an approximately 20% reduction in insulin
      sensitivity (insulin-induced glucose disposal rate/mean insulin concentration
      ratio, P < 0.01) and an approximately 10% reduction in glucose disappearance rate
      (K-value, P < 0.05), whereas these variables were not significantly modified with
      nebivolol. Cardiac output was reduced similarly (P < 0.05) by both drugs at rest
      but forearm blood flow, forearm vascular resistance or total peripheral
      resistance were unaffected. A significant inverse correlation coefficient between
      cardiac output and insulin sensitivity was found at baseline, suggesting that a
      compensatory increase in systemic blood flow occurs in hypertensive patients with
      progressively more marked insulin resistance. This relationship was unaffected by
      nebivolol but was lost with atenolol. CONCLUSIONS: These results indicate that
      insulin sensitivity was not modified significantly by nebivolol, whereas it was
      reduced by atenolol, although blood pressure was decreased to the same extent by
      both drugs. Neither drug induced systemic or forearm vasodilatation but the
      inverse relationship between cardiac output and insulin sensitivity was preserved
      with nebivolol but not with atenolol.

PMID- 11518852
TI  - The prevalence and clinical significance of nocturnal hypertension in pregnancy.
AB  - OBJECTIVE: To determine (a) the prevalence of hypertension during sleep in pre
      eclampsia and gestational hypertension, and (b) whether women with hypertension
      during sleep have worse pregnancy outcomes than hypertensive pregnant women with
      controlled (normal) blood pressure (BP) during sleep. DESIGN: Prospective double
      blind cohort study. SETTING: Inpatients and outpatients managed in a day
      assessment unit (DAU) at St George Hospital, Sydney, Australia. PARTICIPANTS: A
      total of 186 hypertensive pregnant women, 158 of whom had successful 24 h BP
      monitoring; 40% had proteinuric pre-eclampsia (PE), 43% gestational hypertension
      (GH) and 17% essential hypertension (EH). INTERVENTIONS: Blood pressure, 24 h non
      invasive, monitoring (Spacelabs 90207) was undertaken successfully in 158 women
      with PE, GH or EH, whether or not they were receiving antihypertensives. Women
      and clinicians were blinded to results of these BP monitors. Sleep hypertension
      was defined as BP > 117/68 mmHg at 26-30 weeks or > 123/72 mmHg after 30 weeks
      gestation. MAIN OUTCOME MEASURES: Maternal and fetal outcomes were compared
      between women with and without sleep hypertension and the prevalence of sleep
      hypertension was determined. RESULTS: Sleep hypertension was present in 59%, more
      commonly in PE (79%) than GH/EH (45%), P < 0.0001. Sleep hypertensives also had
      higher routine sphygmomanometer BPs [137(10)/91(7) mmHg; mean(SD)] than women
      with normal sleep BP [130(12)/ 87(8) mmHg] P = 0.007, and higher awake ambulatory
      blood pressure monitoring (ABPM) BPs [137(8)/88(7) versus 127(7)/79(6) mmHg], P <
      0.0001. Awake, but not sleep, average heart rate was lower in sleep hypertensives
      [85(11) versus 91 (10) beats per minute, bpm], P = 0.002. Sleep hypertensives had
      a significantly greater frequency of renal insufficiency, liver dysfunction,
      thrombocytopenia and episodes of (awake) severe hypertension (P < 0.05), as well
      as lower birth weight babies [2715 (808) versus 3224(598) g, P < 0.0001].
      CONCLUSIONS: Hypertension during sleep is a common finding in women with
      hypertensive disorders of pregnancy, particularly pre-eclampsia. These women also
      have higher awake BPs and a greater frequency of adverse maternal and fetal
      outcomes. These findings are largely explained by the greater likelihood of pre
      eclamptics having sleep hypertension.

PMID- 11518853
TI  - The hypercoagulable state in sleep apnea is related to comorbid hypertension.
AB  - OBJECTIVE: Obstructive sleep apnea (OSA) is associated with increased prevalence
      of atherosclerotic disease. A hypercoagulable state thought to underly
      atherosclerosis has been described in both OSA and systemic hypertension. We
      wondered about the respective contribution of apnea and hypertension to a
      hypercoagulable state. DESIGN: Eighty-seven subjects with symptoms suggestive of
      OSA, mean age 47 years (range 32-64 years), underwent polysomnography and blood
      pressure (BP) screening. OSA was diagnosed when respiratory disturbance index
      (RDI) > or = 15. Subjects having systolic BP (SBP) > 140 mmHg and/or diastolic BP
      (DBP) > 90 mmHg were classified as having hypertension. Three hypercoagulability
      markers were measured: thrombin/antithrombin III complex (TAT), fibrin D-dimer
      (DD), and von Willebrand factor antigen (vWF:ag). RESULTS: Analysis of variance
      and multiple linear regression were performed on the following four subject
      groups: (1) normotensive non-apneics (n = 19), (2) normotensive apneics (n = 38),
      (3) hypertensive non-apneics (n = 11), and (4) hypertensive apneics (n = 19). OSA
      (groups 2 and 4) had no significant main effect on hemostasis. Hypertensives
      (groups 3 and 4) had higher plasma levels of TAT (median/inter-quartile range,
      148/59-188 versus 77/53-108 pmol/l; P = 0.009) and of DD (376/265-721 versus
      303/190-490 ng/ml; P = 0.040) than normotensives (groups 1 and 2). Across all
      subjects, SBP was the only significant predictor of TAT (P = 0.001) and of DD (P
      = 0.004), whereas DBP was the only significant predictor of vWF:ag (P = 0.029).
      These findings persisted even after controlling for gender, age, body mass index,
      RDI, mean SaO2, and hematocrit. CONCLUSION: Hypercoagulability in OSA is mediated
      by comorbid hypertension and might account for high cardiovascular morbidity in
      OSA in general.

PMID- 11518854
TI  - Myocardial adrenergic dysfunction in rats with transgenic, human renin-dependent
      hypertension.
AB  - OBJECTIVES: We investigated cardiac function in rats transgenic for the human
      renin and angiotensinogen genes (TGR) to test the hypothesis that elevated local
      angiotensin II precipitates adrenergic dysfunction and abnormal contractile
      function. METHODS: Hearts from TGR and Sprague-Dawley control rats, aged 6 weeks,
      were studied using the Langendorff model and papillary muscle preparations (n = 6
      10 per group). Incremental isoproterenol (1 - 1000 nmol/l) and external Ca2+
      concentrations (0.75-6.0 mmol/l) were tested. Cardiac protein and mRNA expression
      levels were determined by Western blot and RNAase protection assay. RESULTS: TGR
      rats showed left ventricular hypertrophy (54%), higher blood pressures (76 mmHg),
      and elevated plasma renin activity (seven-fold) compared to controls (P < 0.01).
      The effect of isoproterenol on TGR rat systolic and diastolic left ventricular
      performance was decreased in both in-vitro models compared to controls (two- to
      threefold, P < 0.01). TGR rat papillary muscles showed impaired force generation
      with abnormal basal and Ca2+-dependent relaxation. Gialpha2 and Gialpha3 protein
      levels were increased (20-30%) and SERCA2a and adenylyl cyclase protein levels
      were decreased (23 and 37%, respectively) in TGR hearts compared to controls,
      while Gsalpha or beta1 and beta2-receptor levels were unchanged. Cardiac
      angiotensin converting enzyme and atrial natriuretic peptide mRNA levels were
      increased more than four-fold in TGR with no differences for the angiotensin
      type1 receptor, beta1-receptor, SERCA2a, phospholamban, adenylyl cyclase V and
      angiotensinogen genes. CONCLUSIONS: TGR rat hearts develop severe adrenergic
      dysfunction with decreased adenylyl cyclase and abnormal intracellular Ca2+
      homeostasis. Our findings emphasize angiotensin II as a major risk factor
      promoting early functional decline in cardiac hypertrophy. The data may have
      implications for patients with activating polymorphisms of the renin-angiotensin
      system and support the need for an early therapeutic intervention.

PMID- 11518855
TI  - Effects of angiotensin II subtype 1 receptor blockade on cardiac fibrosis and
      sarcoplasmic reticulum Ca2+ handling in hypertensive transgenic rats
      overexpressing the Ren2 gene.
AB  - OBJECTIVE: We evaluated the effects of angiotensin II subtype 1 (AT1) receptor
      antagonism on cardiac fibrosis and sarcoplasmic (SR) Ca2+ handling in a
      transgenic rat model of renin-dependent left ventricular (LV) hypertrophy (LVH).
      METHODS: Hypertensive transgenic rats overexpressing the Ren2 gene (TGR(mRen2)27)
      were treated between 10 and 30 weeks of age with the angiotensin II subtype 1
      (AT1) receptor antagonist, eprosartan, in an antihypertensive (Ren2-E60, 60 mg/kg
      per day) and a non-antihypertensive (Ren2-E6, 6 mg/kg per day) dose applied
      intraperitoneally via osmotic-mini-pumps. They were compared to age-matched Ren2
      and Sprague-Dawley (SD) control rats receiving 0.9% NaCl as vehicle via osmotic
      mini-pumps (Ren2-Vehicle, SD-Vehicle, respectively). RESULTS: Systolic blood
      pressure (SBP), LV weight, LV end-diastolic pressure (LVEDP), and cardiac
      fibrosis were elevated in Ren2-Vehicle, while diastolic function (-dP/dt(max))
      and sarcoplasmic reticulum (SR) Ca2+ uptake were decreased in Ren2-Vehicle
      compared to SD-Vehicle (P < 0.05, respectively). SBP was not altered in Ren2-E6,
      but reduced to normotensive levels in Ren2-E60 compared to Ren2-Vehicle and SD
      Vehicle (P < 0.0001). In both Ren2-E6 and Ren2-E60, LV weights were reduced and
      LVEDP and -dP/dt(max)normalized compared to Ren2-Vehicle (P < 0.05). SR Ca2+
      uptake was normalized in both Ren2-E6 and Ren2-E60. Cardiac fibrosis did not
      change in Ren2-E6, but perivascular LV fibrosis and hydroxyprolin content were
      reduced in Ren2-E60 compared to Ren2-Vehicle (P < 0.05, respectively).
      CONCLUSIONS: Normalization of LV SR Ca2+ uptake is an important mechanism by
      which AT1 receptor antagonism improves LV diastolic dysfunction independent from
      a reduction of SBP and cardiac fibrosis in the TGR (mRen2)27 model.

PMID- 11518856
TI  - Left ventricular mass assessed by electrocardiography and albumin excretion rate
      as a continuum in untreated essential hypertension.
AB  - OBJECTIVE: To study an association between albumin excretion rate and left
      ventricular mass (LVM) determined by electrocardiogram (ECG)-based criteria, and
      with respect to ambulatory blood pressure, in patients with newly diagnosed and
      never-treated essential hypertension. METHODS: We measured 24 h ambulatory blood
      pressure, albumin excretion rate and LVM in 74 patients with newly diagnosed
      (within the past year) and never-treated essential hypertension, who were
      admitted to the hypertension clinic (Ulleval University Hospital). Albumin
      excretion rate was evaluated by determination of the albumin:creatinine ratio in
      the first-voided morning urine sample. LVM was assessed by ECG using Cornell
      voltage-QRS duration product and Sokolow- Lyon criteria. RESULTS: Albumin
      excretion rate was significantly related to ambulatory blood pressure. There was
      a weak but significant negative correlation between the decrease in diastolic
      blood pressure during the night and the rate of excretion of albumin. The
      patients classified as dippers had a significantly lower albumin excretion rate
      compared with the non-dippers (1.36+/-0.83 compared with 1.68+/-0.87 mg/mmol; P =
      0.03). LVM was found to be significantly related to ambulatory blood pressure. A
      weak relationship was observed between albumin excretion rate and LVM as
      evaluated by Cornell criterion (r = 0.23, P = 0.045). When only normoalbuminuric
      patients were included (i.e. four patients with microalbuminuria were excluded),
      the relationship was stronger (r = 0.36, P = 0.002). CONCLUSIONS: The present
      findings show a continuous relationship between albumin excretion rate, LVM and
      ambulatory blood pressure in newly diagnosed patients with essential
      hypertension, and suggest the occurrence of early effects on target organs
      (kidneys and heart). These associations were observed using easily applicable
      methods such as ECG monitoring and determination of the albumin:creatinine ratio
      in morning urine samples.

PMID- 11518857
TI  - Blood pressure-independent effect of angiotensin AT1 receptor blockade on renal
      endothelin-1 production in hypertensive uremic rats.
AB  - OBJECTIVE: We recently reported that treatment of uremic rats with reduced renal
      mass with the angiotensin II (Ang II) subtype 1 receptor (AT1) antagonist
      losartan reduces endothelin-1 (ET-1) levels in blood vessels and in glomeruli.
      Although this suggests an important role for Ang II in the modulation of ET-1
      production, the concomitant decrease in blood pressure may also be involved. The
      present study was designed to investigate whether the modulation of ET-1
      production in uremic rats is related to tissue-specific effects of AT1 receptor
      blockade or to the antihypertensive effect of losartan. DESIGN: One week after
      renal mass reduction, uremic rats were treated with the conventional triple
      therapy (TRx) [reserpine (5 mg/l), hydralazine (80 mg/l) and hydrochlorothiazide
      (25 mg/l)] or losartan (20 mg/kg per day) for 6 weeks. Immunoreactive-ET-1 (ir-ET
      1) levels in plasma and urine, as well as in vascular and renal tissues were
      measured by a specific radioimmunoassay after sample extraction and purification.
      RESULTS: Before treatment, systolic blood pressure was significantly higher in
      uremic animals compared to sham-operated controls (165+/-4 versus 123+/-2 mmHg,
      respectively; P < 0.01). Treatment with the TRx or with losartan normalized
      systolic blood pressure in uremic rats, whereas it was further increased in
      untreated uremic animals. At week 6, serum creatinine, proteinuria and urinary ET
      1 and transforming growth factor-beta1 (TGF-beta1) excretion, as well as vascular
      and glomerular ET-1 content were increased in uremic rats compared to the
      controls (P < 0.01). Treatment of uremic rats with the TRx or with losartan
      reduced ET-1 content in the thoracic aorta and the mesenteric arterial bed (P <
      0.01). However, losartan, but not the TRx, significantly attenuated the rise of
      serum creatinine, proteinuria and urinary ET-1 and TGF-beta1 excretion, as well
      as ET-1 content in glomeruli of uremic rats. Compared with the controls, renal
      preproET-1 mRNA expression was also significantly higher in uremic rats.
      Treatment of uremic rats with losartan prevented renal preproET-1 mRNA
      overexpression, indicating that changes in glomerular ET-1 content and urinary ET
      1 excretion were related to modulation of renal ET-1 production. CONCLUSIONS:
      These findings indicate that the effect of losartan on ET-1 production in
      peripheral blood vessels may be mediated, in part, by the reduction of blood
      pressure. In contrast, the reduction of renal ET-1 production is mediated by
      tissue-specific effects of AT1 receptor blockade, and may contribute to the renal
      protective effects of losartan.

PMID- 11518858
TI  - Usefulness and limits of distal echo-Doppler velocimetric indices for assessing
      renal hemodynamics in stenotic and non-stenotic kidneys.
AB  - BACKGROUND: Distal echo-Doppler velocimetric indices are widely used for
      revealing the presence of a renal artery stenosis but there is scarce information
      as to whether they reflect the renal hemodynamics in stenotic and nonstenotic
      kidneys. OBJECTIVES AND METHODS: We evaluated the pulsatility and resistive
      indices (PI and RI), acceleration (A) and acceleration time (At) and correlated
      their values with those of effective renal plasma flow (ERPF), glomerular
      filtration rate (GFR), renal vascular resistance (RVR) and filtration fraction
      (FF) estimated by single kidney scintigraphy in 24 kidneys with 70-95% renal
      artery stenosis (atherosclerotic n = 17, fibromuscular n = 7) and in 27 non
      stenotic kidneys (11 contralateral to renal artery stenosis and 16 of patients
      with essential hypertension). In patients with stenotic kidneys, these
      measurements were repeated within 7 days after a successful percutaneous
      transluminal renal angioplasty (PTRA) (in 11 arteries performed in combination
      with stent implantation). RESULTS: Prior to dilation we found that the stenotic
      kidneys had significantly lower values of ERPF, GFR and higher RVR than the non
      stenotic kidneys and that these hemodynamic alterations were associated with
      those, also statistically significant, of the four velocimetric indices. In non
      stenotic kidneys, there were highly significant relationships between PI and
      ERPF, and RVR (r = -0.68 and 0.81 respectively P < 0.01); similar relationships
      were found for RI (r = -0.67 and 0.78 P < 0.01) whereas no such correlations were
      found between these two velocimetric indices and GFR and FF; also no correlations
      were found between A and Atand ERPF, GFR, RVR and FF. In stenotic kidneys no
      significant correlations were found between any of the velocimetric and the
      hemodynamic indices. Renal artery dilation induced clear cut increments in ERPF,
      GFR and reduction in RVR in post-stenotic kidneys, which were associated with
      normalization of all four velocimetric indices. No relationships were observed
      between the renal hemodynamic and the velocimetric changes induced by dilation;
      however in post-stenotic kidneys the relationships between PI and RI, ERPF and
      RVR were restored as in nonstenotic kidneys. CONCLUSIONS: These data indicate
      that PI and RI can be used to assess ERPF and RVR both in non-stenotic and post
      stenotic kidneys; however, none of the velocimetric indices examined in this
      study can provide valid informations on the renal hemodynamics of stenotic
      kidneys and on their changes induced by PTRA.

PMID- 11518859
TI  - Chronic angiotensin converting enzyme inhibition enhances renal vascular
      responsiveness to acetylcholine in anaesthetized rabbits.
AB  - OBJECTIVE: To determine whether 6 weeks continuous treatment with an angiotensin
      converting enzyme (ACE) inhibitor reduced renal vascular responsiveness in vivo,
      since this treatment results in extensive phenotypic conversion of afferent
      arteriolar cells from contractile to endocrine-like, renin secretory cells.
      METHODS: Enalapril (10 microg/kg per h s.c.) was delivered continuously for 6
      weeks. In anaesthetized rabbits (treated or sham), arterial blood pressure and
      renal blood flow were measured and renal responsiveness tested by constructing
      dose-response curves to bolus doses of phenylephrine, angiotensin II and
      acetylcholine delivered directly into the renal artery. RESULTS: ACE inhibition
      resulted in a significant shift to the left in the renal vascular conductance
      responses to acetylcholine (P < 0.005) and angiotensin II (P < 0.05), indicating
      enhanced, not reduced, responsiveness to these agents. There were no significant
      effects of chronic ACE inhibition on the conductance responses to phenylephrine.
      CONCLUSIONS: Contrary to our hypothesis, 6 weeks ACE inhibition did not reduce
      renal vascular responsiveness to three vasoactive agents, suggesting that the
      phenotypic changes observed in the afferent arterioles and to a lesser extent the
      interlobular arteries, were either insignificant or compensated for by other
      changes in renal circulatory control.

PMID- 11518860
TI  - Renal vascular resistance properties and glomerular protection in early
      established SHR hypertension.
AB  - OBJECTIVE: To characterize the in vivo vascular properties of the spontaneously
      hypertensive rat (SHR) renal vascular bed by examining vascular
      conductance/resistance responsiveness to vasoactive agents in vivo and
      determining whether the filtration surface area of glomerular capillaries is
      reduced. DESIGN AND METHODS: in vivo renal blood flow responses to intrarenally
      administered angiotensin II, phenylephrine and acetylcholine were compared in 10
      week-old SHR and Wistar-Kyoto (WKY) rats using a wide range of doses from near
      threshold to near maximal effect. Unbiased stereological techniques and high
      resolution light microscopy were used to estimate the surface area and length of
      glomerular capillaries, and evidence of capillary damage. RESULTS: The SHR renal
      bed demonstrated significantly enhanced dose-vascular resistance responses to
      vasoconstrictors. For vascular conductance and calculated radius of resistance
      vessels, the SHR curves were significantly lower across the full dilator
      constrictor range examined, but the dose-related changes were similar to those of
      WKY rats. There were only modest enhancements of the renal blood flow responses
      in the SHR, evident only when renal blood flow was reduced by more than 50% SHR
      and WKY rats did not differ in mean glomerular capillary surface area (0.13+/
      0.02 mm2 and 0.14+/-0.02 mm2, respectively) or length (5.76+/-0.85 mm and 5.48+/
      0.90 mm, respectively) nor was there evidence of glomerular capillary damage in
      either strain. CONCLUSIONS: The renal vascular bed of the SHR in vivo exhibits
      reduced vascular conductance across a wide vasomotor range, compatible with
      findings in other vascular beds. We have further shown no evidence of reduced
      glomerular capillary surface area or damage. These findings are compatible with
      the hypothesis that the reduced conductance of the SHR pre-glomerular vasculature
      increases the aorta-capillary pressure gradient thus protecting the glomerular
      capillaries from systemic hypertension at this age.

PMID- 11518861
TI  - Effects of changes in body position on 24 h ambulatory blood pressure.

PMID- 11518862
TI  - San-pin Wang, MD, MPH, DMSC 1920-2001.

PMID- 11518863
TI  - Duplicate publication.

PMID- 11518864
TI  - Re: Duplicate publication.

PMID- 11518865
TI  - Characteristics of persons with syphilis in areas of persisting syphilis in the
      United States: sustained transmission associated with concurrent partnerships.
AB  - BACKGROUND AND GOAL: In areas with persistent syphilis, to characterize persons
      at higher risk for transmitting syphilis. STUDY DESIGN: Cohort study. Structured
      interviews of persons with early syphilis from four research centers were linked
      to outcomes of partner tracing. RESULTS: Of 743 persons with syphilis, 229 (31%)
      reported two or more partners in the previous month, and 57 (8%) received money
      or drugs for sex in the previous three months. Persons with at least one partner
      at an earlier stage of syphilis than themselves were defined as transmitters; 63
      (8.5%) of persons with early syphilis met this definition. Having concurrent
      partners (two or more in one week in the last month) was independently associated
      with being a transmitter. CONCLUSION: Sexual network/behavioral characteristics
      of syphilis patients and their partners, such as concurrency, can help identify
      persons at higher risk for transmitting syphilis who should receive emphasis in
      disease prevention activities.

PMID- 11518866
TI  - Concurrent partnerships and syphilis persistence: new thoughts on an old puzzle.

PMID- 11518867
TI  - Antimicrobial susceptibility of Neisseria gonorrhoeae isolates from three
      Caribbean countries: Trinidad, Guyana, and St. Vincent.
AB  - BACKGROUND: The percentage of Neisseria gonorrhoeae isolates resistant to
      antimicrobial agents commonly used for treatment is unknown in many Caribbean
      countries. GOAL: To determine the antimicrobial susceptibility of N gonorrhoeae
      isolates from Trinidad (144 isolates), Guyana (70 isolates), and St. Vincent (68
      isolates) so baseline data can be established for further studies, and to assist
      in establishing effective treatment guidelines. STUDY DESIGN: Consecutive
      urethral and endocervical specimens from several clinics were collected and
      identified as N gonorrhoeae. Isolates of N gonorrhoeae were tested for their
      susceptibility to penicillin, tetracycline, ceftriaxone, ciprofloxacin,
      spectinomycin, and azithromycin. The presumptive identification of penicillinase
      producing N gonorrhoeae and/or tetracycline-resistant N gonorrhoeae isolates
      based on MIC was confirmed by plasmid and tetM content analysis. RESULTS: High
      percentages of penicillin and/or tetracycline resistance were observed in N
      gonorrhoeae isolates from Guyana (92.9%), St. Vincent (44.1%), and Trinidad
      (42.4%). Isolates from all three countries were susceptible to ceftriaxone,
      ciprofloxacin, and spectinomycin. One penicillinase-producing N
      gonorrhoeae/tetracycline-resistant N gonorrhoeae from Guyana had an MIC of 0.5
      microg/l to ciprofloxacin. This and nine other isolates from Guyana also were
      resistant to azithromycin (defined as MIC > or = 2.0 microg/ml) as well as
      penicillin and tetracycline. A reduced susceptibility to azithromycin was
      displayed by 16% of the isolates from St. Vincent and 72% of the isolates from
      Guyana (MIC, 0.25-1.0 microg/ml). Most penicillinase-producing N gonorrhoeae
      isolates carried Africa-type plasmids (61/90), with 28 of 90 having Toronto-type
      plasmids and a single isolate carrying an Asia-type plasmid. The tetM determinant
      in tetracycline-resistant N gonorrhoeae isolates was predominantly of the Dutch
      type (68/91). CONCLUSIONS: The high prevalence of N gonorrhoeae isolates from 3
      of 21 English- and Dutch-speaking Caricom countries in the Caribbean with either
      plasmid-mediated or chromosomal resistance to penicillin and tetracycline
      supports international observations that these drugs should not be used to treat
      gonococcal infections. The detection of isolates with reduced susceptibility to
      drugs such as azithromycin, which currently are recommended for treatment in the
      region, attest to the importance of the continued monitoring of gonococcal
      antimicrobial susceptibility for the maintenance of effective treatment
      guidelines.

PMID- 11518868
TI  - Factors associated with testing for hepatitis C in an internet-recruited sample
      of men who have sex with men.
AB  - BACKGROUND: Nearly 4 million individuals in the United States (1.8%) have been
      infected with hepatitis C virus, yet few are aware of their infection. GOAL: To
      identify correlates associated with hepatitis C virus testing among a sample of
      men who have sex with men. STUDY DESIGN: Internet communications were used for
      solicitation and collection of data, using a 31-question survey. RESULTS: When
      the study was restricted to men who have sex with men in the United States (n =
      381), 95% of the respondents (n = 361) reported at least one risk factor for
      hepatitis C virus transmission, 39% of these respondents (n = 140) reported
      having been tested for hepatitis C virus. Testing was associated with a history
      of nonsexual risk behavior, increased knowledge of the hepatitis C virus, and
      healthcare provider communication. CONCLUSION: A significant proportion of at
      risk respondents had not been tested. Interventions are needed to increase
      hepatitis C virus knowledge in the community of men who have sex with men, and to
      encourage providers to communicate about hepatitis to the men in this group who
      screen as high risk on the basis of their risk behaviors.

PMID- 11518869
TI  - Reduced susceptibility to azithromycin and high percentages of penicillin and
      tetracycline resistance in Neisseria gonorrhoeae isolates from Manaus, Brazil,
      1998.
AB  - BACKGROUND: The identification of Neisseria gonorrhoeae isolates resistant to
      antimicrobial agents currently recommended for the treatment of gonococcal
      infections continues to escalate globally. Thus, in some areas, resistance to
      fluoroquinolone drugs is commonplace; several reports document resistance to
      third-generation cephalosporins, and the sporadic isolation of spectinomycin
      resistant isolates continues unabated. Gonococcal resistance to azithromycin, an
      antibiotic used for the primary treatment of gonococcal infections in some Latin
      American countries, also has been described. Because the prevalence of resistant
      isolates is insufficiently documented in many areas of Latin America, the
      efficacy of locally recommended therapies for gonococcal infections is often
      unknown. GOAL: To determine the antimicrobial susceptibility and strain types of
      N gonorrhoeae isolates collected in Manaus, Brazil. These data will establish
      antimicrobial susceptibility baseline data for the region as a reference point
      for future surveillance. STUDY DESIGN: Consecutive N gonorrhoeae isolates from
      urethral and endocervical specimens were collected and examined for identity,
      antimicrobial susceptibility, and strain type (plasmid content, tetM type,
      auxotype, and serovar). RESULTS: Most of the isolates (65/81; 85.2%) were
      resistant to tetracycline, penicillin, or both, with the majority (n = 62)
      carrying plasmid-mediated resistance to tetracycline (tetracycline-resistant N
      gonorrhoeae [TRNG]). All of the TRNG contained the Dutch-type tetM plasmid, and
      18 were A/S class NR/IA-02. Penicillinase-producing N gonorrhoeae comprised 8.2%
      (7/81) of the isolates. Of these seven isolates, four also were TRNG, and two
      carried chromosomal resistance to tetracycline. The isolates were susceptible to
      ciprofloxacin, spectinomycin, and ceftriaxone. However, 23 isolates were
      characterized by reduced susceptibility to azithromycin (MIC, 0.25-0.5
      microg/ml), and one isolate had reduced susceptibility to ciprofloxacin (MIC,
      0.25 microg/ml). CONCLUSIONS: This study supports the continued use of third
      generation cephalosporins, spectinomycin, and fluoroquinolone drugs for the
      primary treatment of gonococcal infections in Manaus. The occurrence of isolates
      with reduced susceptibility to azithromycin and ciprofloxacin underscores the
      importance of ongoing antimicrobial susceptibility monitoring to support
      decisions regarding appropriate drugs for the treatment of gonococcal infections.

PMID- 11518870
TI  - Sexual initiation: predictors and developmental trends.
AB  - BACKGROUND: Early initiation of sexual intercourse is associated with increased
      risk for acquiring sexually transmitted diseases. GOAL: To examine variables
      related to sexual initiation and developmental changes in the reasons why
      adolescent girls have sexual intercourse. STUDY DESIGN: A longitudinal study of
      girls recruited from an adolescent medicine clinic was performed. RESULTS:
      Logistic regression showed that girls who described their families as being
      expressive, having a moral-religious emphasis, providing supervision, and having
      greater maternal education, and who experienced menarche at an older age were
      older at sexual initiation. On the basis of contingency analyses, younger girls
      were less likely to report attraction or love, and more likely to report peers
      having sex as a reason for sexual intercourse at initiation. A generalized
      estimating equation analysis indicated that girls at younger ages are more likely
      to report curiosity, a grown-up feeling, partner pressure, and friends having
      sexual intercourse as reasons for intercourse. Girls at older ages are more
      likely to report a feeling of being in love, physical attraction, too excited to
      stop, drunk or high partner, and feeling romantic as reasons for having sexual
      intercourse. CONCLUSIONS: Prevention programs should include a focus on familial
      characteristics and susceptibility to peer norms. They should be conducted with
      sensitivity to the developmental changes in intimate relationships that occur
      during adolescence.

PMID- 11518871
TI  - Sexual initiation and developmental changes.

PMID- 11518872
TI  - Sources of recent sexually transmitted disease (STD)-related health care for STD
      clinic patients.

PMID- 11518873
TI  - Antimicrobial susceptibilities of Neisseria gonorrhoeae in Kigali, Rwanda, and
      trends of resistance between 1986 and 2000.
AB  - BACKGROUND: Plasmid-mediated and chromosomal-mediated resistance of Neisseria
      gonorrhoeae to penicillin, tetracycline, thiamphenicol, and trimethoprim
      sulfamethoxazole has spread dramatically in Africa. Monitoring of antimicrobial
      susceptibility is a key element in the control of sexually transmitted diseases.
      GOAL: To document antimicrobial susceptibilities of gonococci isolated during the
      past 15 years in Kigali, Rwanda. STUDY DESIGN: Minimal inhibitory concentrations
      of recently collected gonococcal isolates of eight antimicrobials were
      determined. The results were compared with data collected for isolates obtained
      since 1986. RESULTS: In 1986, 35% of the gonococcal isolates were penicillinase
      producing N gonorrhoeae. Tetracycline-resistant N gonorrhoeae appeared in 1989.
      The prevalence of penicillinase-producing N gonorrhoeae and tetracycline
      resistant N gonorrhoeae increased significantly to 70.5% and 89.2%, respectively.
      Chromosomal resistance to penicillin, tetracycline, and thiamphenicol increased
      temporarily, then decreased significantly. Chromosomal resistance to trimethoprim
      sulfamethoxazole appeared in 1988 and increased to 21.6%. All the isolates were
      susceptible to ceftriaxone, ciprofloxacin, spectinomycin, and kanamycin.
      CONCLUSIONS: This study illustrated the rapidly increasing frequencies of
      penicillinase-producing N gonorrhoeae and tetracycline-resistant N gonorrhoeae.
      Chromosomal resistance to thiamphenicol and trimethoprim-sulfamethoxazole
      excludes these drugs as alternative treatment. Programs for antimicrobial
      susceptibility surveillance of N gonorrhoeae should urgently be established in
      Africa.

PMID- 11518874
TI  - Condom use among sterilized and nonsterilized Hispanic women.
AB  - BACKGROUND: Women who use sterilization for contraception are at risk for various
      sexually transmitted diseases, unless they use a barrier method. Use of condoms
      is significantly lower among sterilized women than among hormonal-contraceptive
      users. Among Hispanics, women's perception of risk and the influence of male
      partners are strong correlates of dual-method use. Limited data are available
      concerning use of condoms among sterilized women, in particular among Hispanics.
      GOALS: Past and future use of condoms was examined and compared among 224
      sterilized women and 104 hormonal-contraceptive users of Hispanic origin, and the
      reasons for use or nonuse of condoms were examined. STUDY DESIGN: Cross-sectional
      survey. RESULTS: As compared with hormonal-contraceptive users, sterilized women
      were significantly less likely to have used condoms in the 3 months before the
      study or to have plans to use them in the future (P < 0.001). Despite
      similarities between various HIV-related characteristics of sterilized and
      nonsterilized women, the former group had significantly lower perceptions of
      being at risk for both HIV and other sexually transmitted diseases. Sterilized
      women were also more likely to have used condoms for the purposes of dual
      protection from pregnancy. The strongest correlates of consistent condom use by
      both sterilized and nonsterilized Hispanic women were their perceived
      susceptibility to disease, male partners' positive opinion about condoms, and the
      women's ability to use condoms in long-term relationships. Furthermore, the
      practice of concealing the use of a contraceptive from a male partner was not
      uncommon, although this characteristic was not related to increased dual-method
      use. CONCLUSIONS: Sterilized women may be at a higher risk of disease than
      hormonal-contraceptive users. Among Hispanics, women's perception of risk and
      male partners' influences predict whether the women protect themselves from
      pregnancy and disease simultaneously.

PMID- 11518875
TI  - Contraception, unintended pregnancies, and sexually transmitted infections: still
      no simple solutions.

PMID- 11518876
TI  - The choice of antibacterial drugs.

PMID- 11518877
TI  - Transactions of the sixty-third annual meeting of the South Atlantic Association
      of Obstetricians and Gynecologyists. The millennial mark: presidential address.

PMID- 11518878
TI  - Correlation of head-to-body delivery intervals in shoulder dystocia and umbilical
      artery acidosis.
AB  - OBJECTIVE: Our goal was to determine the effect of shoulder dystocia on umbilical
      artery acidosis. STUDY DESIGN: We performed a retrospective analysis of 134
      mother-infant pairs of shoulder dystocia cases at our institution from January 1,
      1994, through December 31, 1997. Cases were identified from the obstetric
      database, and charts were abstracted for demographics, head-to-body delivery
      interval, umbilical blood gas parameters, and neonatal outcome. Pooled student t
      tests were used to compare mean blood gas values with data previously reported
      from our patient population. Regression analysis was performed regarding head-to
      body delivery interval and blood gas parameters. RESULTS: The mean umbilical
      artery pH of shoulder dystocia cases (7.23 +/-.082) was less than the mean
      arterial pH of all vaginal deliveries in our institution (7.27 +/-.069), P <.001.
      Head-to-body delivery intervals (available for 44 cases) were not associated with
      statistically significant alterations in umbilical artery pH (r(2) =.0004),
      PCO(2) (r(2) =.011), or base deficit (r(2) =.006). Increasing head-to-body
      delivery interval was also not significantly correlated with decreasing 5-minute
      Apgar score (r =.0278). CONCLUSION: In our study population, shoulder dystocia
      resulted in statistically significant but clinically insignificant reductions in
      mean umbilical artery blood gas parameters. No statistically significant linear
      relationship was identified between the head-to-body delivery interval and fetal
      acid-base status.

PMID- 11518879
TI  - Understanding evidence-based medicine: a primer.
AB  - Evidenced-based medicine is the concept of formalizing the scientific approach to
      the practice of medicine for identification of "evidence" to support our clinical
      decisions. It requires an understanding of critical appraisal and the basic
      epidemiologic principles of study design, point estimates, relative risk, odds
      ratios, confidence intervals, bias, and confounding. By using this information,
      clinicians can categorize evidence, assess causality, and make evidence-based
      recommendations. Evidence-based medicine allows analysis of complicated material
      so that we can make the best possible clinical decisions for the populations we
      serve.

PMID- 11518880
TI  - A single physician's experience with four thousand six hundred genetic
      amniocenteses.
AB  - OBJECTIVE: We sought to assess changes in indications, technique, successful
      fluid aspiration, and pregnancy outcomes in a large cohort of genetic
      amniocenteses performed by a single physician. STUDY DESIGN: Records were
      reviewed regarding 4600 women who underwent genetic amniocentesis by a single
      physician between 1972 and 2000. Changes in indications, procedural technique,
      ease of performance, amniotic fluid reports, and pregnancy loss rates were
      tabulated and compared over time. RESULTS: The indications for amniocentesis
      changed significantly (P < .0001) over time with the increasing use of maternal
      serum screening studies and fetal assessment by ultrasonography. The ease with
      which clear amniotic fluid was aspirated increased with experience, improvements
      in ultrasound technology, and modifications of amniocentesis technique. Procedure
      related total pregnancy loss rate was 0.95%, and loss rate within 60 days of the
      procedure was 0.55%. Increasing operator experience did not improve the pregnancy
      loss rate significantly. CONCLUSIONS: Successful aspiration of clear amniotic
      fluid increases with amniocentesis experience. Pregnancy outcome did not change
      significantly with increasing amniocentesis experience.

PMID- 11518882
TI  - An update on vulvar cancer.
AB  - Vulvar cancer is a rare gynecologic malignancy whose primary treatment is
      surgical. It is not uncommon for patients to delay seeking medical attention or
      for physicians to delay diagnosing the condition. The most prevalent vulvar
      cancer is squamous cell carcinoma, with vulvar melanoma being the second most
      common. The basic understanding of the anatomy and the mechanisms of lymphatic
      spread have made modifications in surgical technique possible, allowing less
      radical excisions with significantly less morbidity. New approaches using
      lymphatic mapping with sentinel node dissection appear promising for the future
      treatment of early vulvar cancers.

PMID- 11518881
TI  - Maternal serum screening for fetal trisomy 18: benefits of patient-specific risk
      protocol.
AB  - OBJECTIVE: Our goal was to evaluate the effectiveness of two approaches to screen
      pregnancies for trisomy 18. STUDY DESIGN: We analyzed the outcome of all
      pregnancies that were screen positive for trisomy 18 by multiple marker screening
      (alpha-fetoprotein, unconjugated estriol, and human chorionic gonadotropin) from
      May 1993 to June 1998. We compared the results of a fixed cutoff protocol to a
      protocol that incorporates maternal age to generate a patient-specific risk
      figure. RESULTS: A total of 45,145 patients were screened. By using the fixed
      cutoff protocol, 113 patients (0.25%) were screen positive. The risk-based
      approach was associated with a 0.55% screen-positive rate (250 patients). Eight
      of 12 cases (67% detection rate) of trisomy 18 were identified by using the risk
      method, and only 5 cases (42% detection rate) were detected by using the fixed
      cutoff method. By using the risk-based protocol, 21 pregnancies with chromosomal
      abnormalities (8, trisomy 18; 7, triploidy; 5, trisomy 21; and 1, mosaic
      45X/46XX) were detected. Subsequent fetal death occurred for 42 patients whose
      fetuses were chromosomally normal and without structural malformations.
      CONCLUSION: The patient-specific risk protocol to screen for trisomy 18 is a
      beneficial adjunct to screening programs already in place for Down syndrome and
      neural tube defects. Patients found to be screen positive for trisomy 18 are at
      significant risk for adverse pregnancy outcome.

PMID- 11518883
TI  - Gamete retrieval in terminal conditions.
AB  - There has been a growing interest and requests by patients facing intensive
      chemotherapy or surgically ablative procedures for gamete retrieval and
      preservation for future procreative efforts. There are technical difficulties in
      this area but little ethical discomfort. More troubling are the issues that arise
      with a terminally ill, incapable patient-one who is in a persistent vegetative
      state or who is declared brain dead or who is neurologically devastated with no
      hope for recovery, but not yet in either of the above states-or with a person who
      has suddenly died. In these cases, the surviving spouse, partner, or family
      members may request gamete retrieval for future reproductive efforts. Discussion
      of this topic within the Ethics Consultation Service at the University of
      Virginia demonstrated a need for development of insight derived from facts and
      ethical deliberation to help formulate a policy that would apply to such cases. A
      group was assembled with the expertise to explore the issue and to help formulate
      a policy that could be suggested for adoption by the hospital administration. The
      group consisted of a urologist with experience in sperm retrieval from terminally
      ill patients; the director of the laboratory supporting the assisted reproductive
      facility in the Department of Obstetrics and Gynecology; the chairperson of the
      Ethics Consultation Service (who is also a neonatologist); and 2 members of the
      Ethics Consultation Service, one a genetic counselor and the other an
      obstetrician-gynecologist with a master's degree in biomedical ethics. Current
      literature was reviewed, the expertise of the urological member and the
      reproductive laboratory director was explored, and the insight of the members of
      the Ethics Consultation Service was added. We explored the technical aspects of
      both male and female gamete retrieval and preservation and the reproductive
      potential of these stored gametes. We present a review of the current literature
      on both the technical and ethical aspects of the topic. Finally, we present a
      policy that we deem acceptable for adoption and that should be of value to other
      practitioners and facilities as they contemplate facing requests for gamete
      retrieval.

PMID- 11518884
TI  - Liquid-based cervical cytologic smear study and conventional Papanicolaou smears:
      a metaanalysis of prospective studies comparing cytologic diagnosis and sample
      adequacy.
AB  - OBJECTIVE: We sought to evaluate the cytologic diagnosis and sample adequacy of
      the liquid-based cervical cytologic smear (ThinPrep) compared with that of the
      conventional Papanicolaou smear. STUDY DESIGN: Prospective studies of ThinPrep
      and conventional Papanicolaou smears were analyzed for cytologic diagnosis and
      sample adequacy. Computerized databases, references in published studies, and
      index reviews published in English were used to identify direct-to-vial and split
      sample clinical trials of cervical smears performed by conventional and liquid
      based techniques. Only published studies that used the Bethesda system
      nomenclature with clearly documented outcome data were included. Each trial was
      assessed for the quality of its method, inclusion and exclusion criteria,
      adequacy of randomization, sampling protocols, definition of outcome, and
      statistical analyses. RESULTS: Twenty-five studies met inclusion criteria for
      this review. Odds ratios with 95% confidence intervals were calculated for each
      outcome. Estimates of odds ratios and risk differences for dichotomous outcomes
      were calculated by use of random and fixed-effects models. Homogeneity was tested
      across the studies. Results indicate that the ThinPrep test is as good as or
      superior to the conventional Papanicolaou smear in diagnosing uterine cervical
      premalignant abnormalities. Also the ThinPrep test provides improved sample
      adequacy when compared with the conventional Papanicolaou test. CONCLUSION: The
      ThinPrep test improved sample adequacy and led to improved diagnosis of low-grade
      and high-grade squamous intraepithelial lesions. However, there is no difference
      in the rate of atypical cells of undetermined significance diagnosis between
      ThinPrep and conventional smear groups. The added cost of ThinPrep cytologic
      screening and, hence, its cost-effectiveness are not evaluated in this study.

PMID- 11518885
TI  - Hormone replacement therapy in postmenopausal women: utilization of health care
      resources by new users.
AB  - OBJECTIVE: To determine health care resource use by new postmenopausal users of
      hormone replacement therapy. METHOD: We used the Saskatchewan Health
      administrative databases, which include a health insurance registration file, a
      cancer registry, and files with data on outpatient prescription drugs, hospital
      services, and physician services. Our population included postmenopausal women
      aged 55 years and over with intact uteri taking hormone replacement therapy for
      long-term prevention benefits, and an equal number of postmenopausal women with
      intact uteri with no medical contraindications to hormone replacement therapy but
      who did not use the therapy during the study period. RESULTS: The population in
      our analysis included 2632 women with new episodes of hormone replacement
      therapy, all with at least 3 years of follow-up. Only 42% of new hormone
      replacement therapy users continuously took HRT during the first year after
      initiation of their first new episode; a third of these were full-year users in
      the second year. New users of hormone replacement therapy over a 6-year follow-up
      period had significantly higher rates of medical care contact for diagnoses of
      menopausal disorders in the first year of HRT compared with subsequent years. We
      also found slightly elevated numbers of visits to primary care physicians and
      obstetrician-gynecologists and slightly increased use of endometrial biopsies and
      dilation and curettage procedures in the first year of hormone replacement
      therapy, compared with subsequent years. CONCLUSION: New users of hormone
      replacement therapy had higher rates of medical care for menopausal disorders in
      their first year of therapy compared with rates in subsequent years. After
      discontinuing hormone replacement therapy, utilization of medical care decreased
      dramatically.

PMID- 11518886
TI  - Scheduled cesarean delivery and the prevention of human immunodeficiency virus
      transmission: a survey of practicing obstetricians.
AB  - OBJECTIVE: To characterize practice patterns among obstetrician-gynecologists
      with respect to delivery for human immunodeficiency virus (HIV)-seropositive
      women, following publication of the 1999 American College of Obstetricians and
      Gynecologists (ACOG) Committee Opinion regarding scheduled cesarean delivery for
      HIV-infected patients. METHODS: A 25-question, multiple-choice survey was mailed
      to 2000 randomly selected obstetrician-gynecologists: 1000 maternal-fetal
      medicine specialists and 1000 general obstetrician-gynecologists. Mailing
      addresses were obtained from the 1999-2000 editions of the Society for Maternal
      Fetal Medicine (SMFM) and ACOG membership directories. Information was requested
      about general perceptions of the 1999 ACOG Committee Opinion and about practice
      patterns with respect to management of HIV disease in pregnancy. Data were
      analyzed by using descriptive statistics and the chi-square test. Any P values
      <.05 were considered significant. RESULTS: After a single mailing we received 512
      responses (25.6%), including 433 (43%) from SMFM members and 79 (8%) from ACOG
      members. Among the respondents, 47% disagreed with the current scientific
      validity of the 1999 ACOG Committee Opinion recommendation to offer cesarean
      delivery to all HIV-seropositive pregnant women. No statistically significant
      differences were detected in the demographic profiles, years of experience, or
      practice settings of participants who agreed with the scientific validity when
      compared to those who did not. Most respondents used viral load detection (87%)
      monitored on a trimester basis (67%) for clinical management decisions. Most
      practitioners (72%) do not recommend cesarean delivery for women who are
      compliant with antiretroviral therapy and who have undetectable viral loads
      regardless of CD4 counts. However, most practitioners (67%) do recommend cesarean
      delivery for those compliant women with detectable viral loads, irrespective of
      CD4 counts (67%). CONCLUSIONS: There is considerable disagreement among
      practicing obstetricians with respect to the 1999 ACOG Committee Opinion
      recommendation to offer cesarean delivery to all HIV-seropositive women. Most
      physicians use viral load detection to assist with the counseling in delivery
      options for HIV-infected pregnant women.

PMID- 11518887
TI  - Predictors of success with the use of donor sperm.
AB  - OBJECTIVE: This study was undertaken to assess the effect of multiple factors
      that influence the success rate and time to conception among couples undergoing
      donor sperm insemination. STUDY DESIGN: A retrospective analysis of 960 cycles of
      frozen donor sperm insemination was performed at the University of Florida. Cycle
      pregnancy rates and cumulative probability of pregnancy were compared using
      several variables. RESULTS: The pregnancy rate was 12.1% per treatment cycle, and
      the cumulative probability of pregnancy exceeded 80% for the entire cohort.
      Seventy percent of pregnancies resulted in a liveborn infant. Age had a profound
      impact on the cycle pregnancy rate. The cycle pregnancy rates for women younger
      than 30 years, between the ages of 30 and 35 years, between the ages of 35 and 40
      years, and older than 40 years were 15.8%, 14.6%, 8.2%, and 0%, respectively.
      There was a trend toward higher cycle pregnancy rates in women with prior
      pregnancies versus women without prior pregnancies of 14.4% and 12.3%,
      respectively. Parity had no effect on the cycle pregnancy rate or the cumulative
      probability of pregnancy. There was a trend toward higher cumulative probability
      of pregnancy in women whose partners were azoospermic versus oligospermic. There
      was no difference in pregnancy rates obtained with the Percoll wash gradient
      versus the Isolate gradient. At >20 million total motile sperm per insemination,
      there was no threshold above which the pregnancy rate was improved. CONCLUSION:
      The most significant influence on pregnancy rates in the donor sperm insemination
      program at the University of Florida was maternal age. Nulligravidity and a
      diagnosis of mild oligospermia in the man may have a negative impact on pregnancy
      rates.

PMID- 11518888
TI  - Obstructive Mullerian anomalies: case report, diagnosis, and management.
AB  - Many factors affect the development of the female reproductive tract. Obstructive
      anomalies prevent normal menstruation, allow for collection of blood in the
      uterus and the vagina, and may increase the incidence of retrograde menstruation.
      A high index of suspicion is necessary to diagnose these disorders, and an
      adequate workup is essential. This report will present a case of obstructive
      longitudinal vaginal septum. The workup and operative findings will be described,
      followed by a classification and discussion of other obstructive Mullerian
      anomalies. The incidence, workup, and management will be reviewed.

PMID- 11518889
TI  - The routine use of cystoscopy with the Burch procedure.
AB  - OBJECTIVE: We sought to determine the incidence of unsuspected injury to the
      lower urinary tract as detected by intraoperative cystoscopy when the Burch
      procedure is performed. STUDY DESIGN: We reviewed the records of 181 women who
      underwent pelvic surgery, which included a Burch retropubic urethropexy for
      genuine stress urinary incontinence, between Jan 1, 1998, and Dec 31, 1999. All
      patients underwent intraoperative cystoscopy at the completion of the Burch
      procedure after the administration of intravenous indigo carmine dye. RESULTS:
      There were 6 (3.3%) injuries to the lower urinary tract. Five of the injuries
      were cystotomies that had been recognized during operation. One obstructed left
      ureter was detected by cystoscopy and relieved by the release of left paravaginal
      repair sutures. No unsuspected injuries that were detected by cystoscopy were
      attributable to the Burch procedure. CONCLUSIONS: The lower urinary tract injury
      rate was 3.3%. All but one injury was recognized before cystoscopy. The one
      injury was attributed to concomitant paravaginal repair and not to the Burch
      procedure.

PMID- 11518890
TI  - Mode of delivery for the morbidly obese with prior cesarean delivery: vaginal
      versus repeat cesarean section.
AB  - OBJECTIVE: We sought to describe the peripartum outcome of women weighing >300
      pounds (135 kg) who were candidates for trial of labor after a prior cesarean
      delivery. STUDY DESIGN: All pregnant women who weighed in excess of 300 pounds
      and had a prior cesarean delivery were included in this prospective
      investigation. Student t test, chi(2) analysis, or Fisher exact tests were used.
      Odds ratios and 95% confidence intervals were calculated. P <.05 was considered
      significant. RESULTS: During a 2-year period, 69 patients met the inclusion
      criteria; 39 (57%) underwent an elective repeat cesarean delivery, and 30 (43%)
      women attempted a vaginal delivery after prior cesarean delivery. The
      demographics of age, race, gravidity, maternal weight, and preexisting medical
      conditions were similar for the two groups. Vaginal birth after prior cesarean
      delivery occurred in 13% (4/30). Reasons for failure included a labor arrest
      disorder in 46%, fetal distress in 38%, and failed induction in 15%. The rates of
      endometritis and wound breakdown were higher in the women undergoing trial of
      labor (30% and 23%, respectively) than in those undergoing repeat elective
      cesarean delivery (20% and 8%). The combined infectious morbidity rate was
      significantly higher for women attempting trial of labor (53%) than those
      undergoing elective repeat cesarean delivery (28%; odds ratio 1.78, 95%
      confidence intervals 1.05, 3.02). CONCLUSION: The success rate for a vaginal
      delivery in the morbidly obese woman with a prior cesarean delivery is less than
      15%, and more than half of the patients undergoing a trial of labor have
      infectious morbidity.

PMID- 11518891
TI  - Hepatitis B immunization in postpartum women.
AB  - OBJECTIVE: To investigate the acceptance and efficacy of hepatitis B immunization
      in women during the postpartum period. STUDY DESIGN: A group of 157 consecutive
      women who were delivered of neonates between 1994 and 1999 under the care of a
      private, full-time faculty-based practice of obstetrics and gynecology
      participated in the study. All patients were screened for hepatitis B surface
      antigen and antibody during their pregnancy. Susceptible patients eligible for
      hepatitis B immunization were offered the vaccine in the immediate postpartum
      period. The planned vaccine administration was a series of 3 intramuscular
      injections, with the second injection given 4 weeks later and the third given 6
      months after the initial injection. Rescreening for hepatitis B surface antibody
      titers was performed at a visit after the last injection. Response to the
      immunization series was evaluated according to rate of acceptance, compliance,
      and achievement of seroprotection. RESULTS: Thirteen (8%) patients had been
      immunized previously and had antibodies, whereas 8 (5%) patients had serologic
      evidence of a previous infection. Of the 136 patients eligible for the study, 113
      (83%) agreed to participate, 16 (12%) declined, and 7 (5%) moved away from New
      York right after delivery. Of the 113 participants, 104 (92%) patients received
      at least 2 vaccine injections, with 80 (71%) completing 3 injections. Among
      patients who had postvaccinal antibody titers, 66 of 69 (96%) of the group that
      received 3 injections and 9 (75%) of 12 of the group that received 2 injections
      were found to have antibodies. CONCLUSION: Hepatitis B immunization in the
      postpartum period is feasible and effective.

PMID- 11518892
TI  - The G-spot: a modern gynecologic myth.
AB  - The G-spot is an allegedly highly erogenous area on the anterior wall of the
      human vagina. Since the concept first appeared in a popular book on human
      sexuality in 1982, the existence of the spot has become widely accepted,
      especially by the general public. This article reviews the behavioral,
      biochemical, and anatomic evidence for the reality of the G-spot, which includes
      claims about the nature of female ejaculation. The evidence is far too weak to
      support the reality of the G-spot. Specifically, anecdotal observations and case
      studies made on the basis of a tiny number of subjects are not supported by
      subsequent anatomic and biochemical studies.

PMID- 11518893
TI  - Treatment of complicated Candida vaginitis: comparison of single and sequential
      doses of fluconazole.
AB  - OBJECTIVE: An attempt was made to validate recent recommendations that women with
      complicated Candida vaginitis (severe or recurrent, non-albicans Candida spp or
      abnormal host) require longer-duration antifungal therapy to achieve clinical
      cure and mycologic eradication. STUDY DESIGN: A prospective, multicenter,
      randomized, double-blind study was performed comparing a single dose of 150 mg of
      fluconazole with 2 sequential 150-mg doses of fluconazole given 3 days apart.
      RESULTS: Five hundred fifty-six women with severe or recurrent Candida vaginitis
      were enrolled, and 398 had at least one postbaseline evaluation (intent to treat)
      and of these 309 were fully evaluable (efficacy-valid). At baseline, 92% of
      vaginal isolates were Candida albicans. The 2-dose fluconazole regimen achieved
      significantly higher clinical cure rates in women with severe vaginitis when
      evaluated on day 14 (P =.015) and higher clinical and mycologic responses
      persisted at day 35. Women with recurrent but not severe vaginitis did not
      benefit clinically short term by the additional fluconazole dose. Multivariate
      logistic regression analysis showed that being infected with non-albicans Candida
      predicted significantly reduced clinical and mycologic response regardless of
      duration of therapy. Fluconazole therapy was well tolerated and free of serious
      adverse effects. CONCLUSION: Treatment of Candida vaginitis requires
      individualization, and women with severe Candida vaginitis achieve superior
      clinical and mycologic eradication with a 2-dose fluconazole regimen.

PMID- 11518894
TI  - Radical abdominal trachelectomy and pelvic lymphadenectomy with uterine
      conservation and subsequent pregnancy in the treatment of early invasive cervical
      cancer.
AB  - BACKGROUND: Recently, pregnancies in patients after radical vaginal trachelectomy
      and laparoscopic pelvic lymphadenectomy have been reported. Radical abdominal
      trachelectomy and pelvic lymphadenectomy with uterine conservation has been
      previously described; however, subsequent outcome and pregnancy has not. METHODS:
      Three patients with cervical carcinoma, 1 with stage IA1 with lymph-vascular
      space invasion and 2 with stage IA2, were treated with radical abdominal
      trachelectomy and pelvic lymphadenectomy with uterine conservation. RESULTS: All
      patients underwent the planned procedure with no significant intraoperative or
      postoperative complications. All patients had return to normal menstrual
      function. One patient had a successful pregnancy delivered at 39 weeks by
      cesarean section and is now subsequently pregnant with a second pregnancy.
      CONCLUSION: Radical abdominal trachelectomy is a technically feasible operation
      that uses operative techniques familiar to the American-trained gynecologic
      oncologist and results in wider parametrial resection than radical vaginal
      trachelectomy. In young patients desiring to retain fertility, successful
      pregnancies after radical abdominal trachelectomy are possible. Intraoperative
      and postoperative complications are likely to be lower with an abdominal versus a
      vaginal approach. Long-term survival of patients treated with radical
      trachelectomy for early invasive cervical cancer are yet to be determined.

PMID- 11518895
TI  - Defense factors of vaginal lactobacilli.
AB  - OBJECTIVE: To determine the antagonistic relationship between vaginal
      lactobacilli and endogenous vaginal microflora. STUDY DESIGN: Twenty-two
      Lactobacillus strains were studied for the production of lactic acid, hydrogen
      peroxide, and bacteriocin. RESULTS: Under standardized growth conditions, most
      strains increased their biomass by more than 4 times. Lactobacillus species grew
      best at a pH > or = 4.5, and growth was retarded at a pH < 4.5. Lactic acid
      levels were 0.68 to 2.518 mg/mL and were not related to the number of cells or
      the pH of media. The pH of the media was caused by the secretion of lactic and
      other organic acids. Approximately 80% of the strains produced H(2)O(2) and were
      graded as 2+ in one third of the strains and 1+ in others. No statistical
      correlation was found between H(2)O(2) lactic acid and bacteriocin production.
      Bacteriocin activity was tested on 4 strains of Gardnerella vaginalis.
      Approximately 80% of the lactobacilli tested produced bacteriocin that inhibited
      growth of G vaginalis. Six of the strains did not produce bacteriocin. Thirteen
      strains produced all 3 defense factors, whereas the others lacked 1 or 2
      properties. CONCLUSIONS: Lactobacillus species grow best at a pH > 4.5. The pH of
      the media is dependent on the cell mass and on all organic acids produced by
      Lactobacillus species. Although all species produce organic acids, not all
      produce H(2)O(2) and bacteriocin. Not all strains of G vaginalis can be inhibited
      by lactobacilli-producing bacteriocin.

PMID- 11518896
TI  - Hormonal contraception and risk of sexually transmitted disease acquisition:
      results from a prospective study.
AB  - OBJECTIVES: To examine the relationship between use of oral contraceptive pills
      or depot medroxyprogesterone acetate and sexually transmitted disease
      acquisition. STUDY DESIGN: Prospective cohort included 948 Kenyan prostitutes.
      Multivariate Andersen-Gill proportional hazards models were constructed,
      adjusting for sexual behavioral and demographic variables. RESULTS: When compared
      with women who were using no contraception, users of oral contraceptive pills
      were at increased risk for acquisition of chlamydia (hazard ratio, 1.8; 95%
      confidence interval, 1.1-2.9) and vaginal candidiasis (hazard ratio, 1.5; 95%
      confidence interval, 1.2-1.9) and at decreased risk for bacterial vaginosis
      (hazard ratio, 0.8; 95% confidence interval, 0.7-1.0). Women using depot
      medroxyprogesterone acetate had significantly increased risk of chlamydia
      infection (hazard ratio, 1.6; 95% confidence interval, 1.1-2.4) and significantly
      decreased risk of bacterial vaginosis (hazard ratio, 0.7; 95% confidence
      interval, 0.5-0.8), trichomoniasis (hazard ratio, 0.6; 95% confidence interval,
      0.4-1.0), and pelvic inflammatory disease (hazard ratio, 0.4; 95% confidence
      interval, 0.2-0.7). Consistent condom use was associated with significantly
      decreased risk of gonorrhea, chlamydia, genital ulcer disease, bacterial
      vaginosis, and pelvic inflammatory disease. CONCLUSIONS: The use of oral or
      injectable hormonal contraception altered susceptibility to sexually transmitted
      diseases, which may in turn influence transmission of human immunodeficiency
      virus type 1. Consistent condom use was protective with regards to sexually
      transmitted disease and should be encouraged for the prevention of sexually
      transmitted disease and human immunodeficiency virus type 1 among women who use
      hormonal contraception.

PMID- 11518897
TI  - Factors associated with endometrial thickness and uterine size in a random sample
      of postmenopausal women.
AB  - OBJECTIVE: The objective of this study was to investigate factors possibly
      associated with endometrial thickness and uterine size in a random sample of
      postmenopausal women. STUDY DESIGN: A random sample (n = 1000) of the total
      population of women 45 to 80 years of age, resident in the city of Goteborg, was
      invited to attend for a transvaginal sonography examination. Eight hundred twenty
      seven women accepted the invitation and underwent a gynecologic and a
      transvaginal sonography examination with measurement of endometrial thickness and
      uterine size. The women's weight and height were measured and a blood sample for
      analysis of serum estradiol and follicle-stimulating hormone was taken. The women
      also provided information regarding previous medical and gynecologic history,
      possible medication, and smoking habits. RESULTS: Five hundred fifty-nine women
      were postmenopausal, and 183 (33%) of the postmenopausal women were taking some
      form of hormonal substitution. Factors associated with endometrial thickness and
      uterine size were analyzed by means of univariate and stepwise multiple
      regression analyses. The current use of hormone replacement therapy was the most
      important factor associated with both endometrial thickness and all the uterine
      size parameters studied. The presence of fibroids was also associated with
      endometrial thickness. Other factors shown to be associated with uterine size
      were age, parity, smoking, hypertension, and the presence of diabetes mellitus.
      CONCLUSIONS: Several of the known risk factors for endometrial cancer were shown
      to be associated with endometrial thickness and uterine size parameters.

PMID- 11518898
TI  - Evaluation of the prognosis of in vitro fertilization pregnancies with initially
      low serum human chorionic gonadotropin levels.
AB  - OBJECTIVE: The objective of this study was to investigate the prognostic
      significance of initially low serum early human chorionic gonadotropin levels in
      in vitro fertilization pregnancies that progress to an intrauterine gestational
      sac. STUDY DESIGN: This retrospective cohort study compared 65 in vitro
      fertilization pregnancies with an initial human chorionic gonadotropin value at 4
      weeks of < or =20 mIU/mL with 130 pregnancies with human chorionic gonadotropin
      values >20 mIU/mL. All pregnancies had a singleton intrauterine sac at 6 weeks'
      gestational age. Spontaneous abortion rates and pregnancy complications were
      compared. RESULTS: Women with a low initial serum human chorionic gonadotropin
      level showed a statistically significant increase in first-trimester pregnancy
      loss (36.5% vs 9.2%; odds ratio, 5.7; 95%; confidence interval, 2.6, 12.4; P
      <.0001). Once pregnancies progressed to 13 weeks, there were no significant
      differences. CONCLUSIONS: In vitro fertilization pregnancies with a low initial
      human chorionic gonadotropin value, despite progressing to a gestational sac, are
      at an increased risk of spontaneous abortion.

PMID- 11518899
TI  - Patients with psychiatric disorders in gynecologic practice.
AB  - OBJECTIVE: The relationship between different gynecologic complaints and somatic
      symptoms was studied in a gynecologic population in which the prevalence of
      psychiatric disorders had been established. STUDY DESIGN: The prevalence of
      depression and anxiety in the unselected population of 1013 subjects was 27.2%
      and 12.1%, respectively, as assessed by the Primary Care Evaluation of Mental
      Disorders (PRIME-MD). The subjects' medical charts were reviewed after the PRIME
      MD diagnosis was made. RESULTS: Depression and anxiety disorders were
      significantly more common among those seeking care for abdominal pain, those who
      made frequent and unscheduled visits, and those who were hospitalized for acute
      care. All the physical symptoms indicated in the PRIME-MD Patient Health
      Questionnaire were more common among women with a psychiatric diagnosis compared
      with controls. CONCLUSIONS: The majority of cases of depression and anxiety in
      women are undiagnosed and untreated, and patients with these disorders often
      present with physical symptoms. Because gynecologic outpatients with abdominal
      pain, frequent and unscheduled visits, and admissions due to acute illness are
      more likely to have a psychiatric disorder, it is desirable that gynecologists
      recognize and treat these problems.

PMID- 11518900
TI  - Prolonged periods without food intake during pregnancy increase risk for elevated
      maternal corticotropin-releasing hormone concentrations.
AB  - OBJECTIVE: Fasting during pregnancy stimulates preterm delivery in animals and
      increases women's risk for preterm delivery. Fasting stimulates hypothalamic
      corticotropin-releasing hormone production in animals. Elevated maternal
      corticotropin-releasing hormone concentrations are associated with preterm birth.
      We hypothesized that prolonged periods without food during pregnancy increase
      maternal corticotropin-releasing hormone concentrations, which lead to preterm
      delivery. STUDY DESIGN: In the Behavior in Pregnancy Study, we examined prolonged
      periods without eating during pregnancy and corticotropin-releasing hormone
      concentrations and gestational age at delivery with multivariate logistic
      regression analysis (n = 237). RESULTS: Prolonged periods without food lasting 13
      hours or longer were associated with elevated maternal corticotropin-releasing
      hormone concentrations compared with prolonged periods without food lasting less
      than 13 hours at two time points during pregnancy, controlling for pregravid body
      mass index, energy intake, income, race, smoking, and maternal age (18-20 weeks:
      adjusted odds ratio, 2.5; 95% CI, 0.9-7.1; 28-30 weeks: adjusted odds ratio, 1.7;
      95% CI, 0.7-4.2). There was an inverse, linear relationship between maternal
      corticotropin-releasing hormone concentrations and gestational age at delivery.
      CONCLUSIONS: Prolonged periods without food intake during pregnancy are
      associated with elevated maternal corticotropin-releasing hormone concentrations
      and with preterm delivery.

PMID- 11518901
TI  - Clinical impact of mild carbohydrate intolerance in pregnancy: a study of 2904
      nondiabetic Danish women with risk factors for gestational diabetes mellitus.
AB  - OBJECTIVE: The objective was to study the clinical impact of mild carbohydrate
      intolerance in pregnant women with risk factors for gestational diabetes
      mellitus. STUDY DESIGN: This was a historical cohort study of 2904 pregnant women
      examined for gestational diabetes on the basis of risk factors. Information on
      oral glucose tolerance test results and clinical outcomes was collected from
      laboratory charts and medical records. RESULTS: The following outcomes increased
      significantly with increasing glucose values during the oral glucose tolerance
      test: shoulder dystocia, macrosomia, emergency cesarean section, assisted
      delivery, hypertension, and induction of labor. However, when corrections were
      made for other risk factors, hypertension and induction of labor were only
      marginally associated with glucose levels. CONCLUSION: In a group of nondiabetic
      pregnant women with risk factors for gestational diabetes, there was a graded
      increase in the frequency of shoulder dystocia and other maternal-fetal
      complications with increasing glucose levels during an oral glucose tolerance
      test.

PMID- 11518902
TI  - Nitric oxide signaling mechanisms in the forearm vasculature of pregnant women.
AB  - During pregnancy, forearm blood flow and constrictor responses to nitric oxide
      synthase inhibition are enhanced. Responses to brachial artery infusion of N(G)
      monomethyl-L -arginine in pregnant women who have normal resting forearm blood
      flow and in pregnant women who have norepinephrine-induced reduced forearm blood
      flow were no different. Mechanisms independent of acute flow effects may account
      for the enhanced vascular nitric oxide activity during pregnancy.

PMID- 11518903
TI  - Computerized analysis of acute and chronic changes in fetal heart rate variation
      and fetal activity in association with maternal smoking.
AB  - OBJECTIVE: To investigate the acute and chronic changes in fetal heart rate and
      fetal activity in association with maternal smoking by means of a computerized
      fetal behavior assessment program. STUDY DESIGN: In 13 term nonsmokers and 13
      term smokers, fetal behavior was analyzed for 2 consecutive periods of >60
      minutes. In between these 2 periods, the smokers were allowed to smoke 1
      cigarette, the nonsmokers were allowed a short break of comparable time span.
      Fetal heart rate variation and fetal activity were recorded by a single 1.5-MHZ
      ultrasound transducer. The percentage of time spent in low and high fetal heart
      rate variation and fetal activity were analyzed by computer before and after the
      short break for nonsmokers and before and after the smokers smoked the 1
      cigarette. Smoking-induced changes in Doppler umbilical artery recordings were
      also investigated. Chronic exposure to cigarette smoke was objectively evaluated
      by measuring the carbon monoxide concentration in expired air in all
      participating women after breath holding. RESULTS: Fetuses chronically exposed to
      cigarette smoke spent significantly more time in a low fetal heart rate variation
      pattern, while fetal activity was decreased both in high and low fetal heart rate
      variation periods. After maternal smoking, no acute changes were observed in
      fetal heart rate variation, yet a reduction in fetal activity was noted; however,
      this only reached statistical significance in periods of high fetal heart rate
      variation. No significant change in mean fetal heart rate was observed, yet a
      significant reduction in the frequency of accelerations was noted. Smoking caused
      an acute and transient increase in the mean pulsatility index in the umbilical
      artery. CONCLUSION: The computer program was able to detect changes in fetal
      behavioral variables in association with acute and chronic smoking. These changes
      may be suggestive of altered neurodevelopmental maturation possibly resulting
      from chronic fetal hypoxemia. This computer program offers a real possibility
      that analysis of fetal behavioral variables can be brought into routine clinical
      practice. Incorporating an analysis of these behavioral variables into smoking
      cessation programs may render them more successful.

PMID- 11518904
TI  - Anal function: effect of pregnancy and delivery.
AB  - OBJECTIVE: To investigate the effect of pregnancy and delivery on anal
      continence, sensation, manometry, and sphincter integrity. STUDY DESIGN: Two
      hundred eighty-six nulliparous women in the third trimester completed a symptom
      questionnaire and underwent anorectal sensation and manometric evaluations. Three
      months postpartum, 161 women returned and the questionnaires and investigations
      were repeated together with anal endosonographic examinations. RESULTS: The
      prevalence of fecal urgency before, during, and after pregnancy was 1%, 9.4%, and
      10.5%, respectively; the prevalence of anal incontinence before, during, and
      after pregnancy was 1.4%, 7.0%, and 8.7%, respectively. Vaginal delivery,
      particularly instrumental, resulted in a decrease in anal squeeze pressures (P
      =.015) and resting pressures (P =.002) but had no effect on anal sensation.
      Postpartum anal endosonographic examination revealed sphincter disruption in 38%
      of women. There was no relationship between symptoms and anal manometry,
      sensation, or sphincter integrity. Vaginal delivery (P <.0001) and perineal
      trauma (P <.001) were significantly associated with sphincter defects.
      CONCLUSION: Vaginal delivery is associated with a decrease in anal pressures and
      increased anal sphincter trauma but has no effect on anal sensation. These
      changes were not related to anal symptoms.

PMID- 11518905
TI  - A survey of dietary supplement use during pregnancy at an academic medical
      center.
AB  - OBJECTIVE: This study examined the usage patterns of dietary supplements during
      pregnancy, providing information about type of supplements used, prevalence of
      use, and rationale for use. STUDY DESIGN: A survey was distributed to pregnant
      patients who were touring the University of California, San Francisco birthing
      center or who were receiving care at the University of California, San Francisco
      Women's Health Clinic between November 1999 and March 2000. RESULTS: Of the 150
      surveys completed, 20 women (13%) used dietary supplements during pregnancy. The
      most common products were echinacea (4/45, 8.9%), pregnancy tea (4/45, 8.9%), and
      ginger (3/45, 6.7%). The most common reasons for beginning or discontinuing use
      of dietary supplements were to relieve nausea and vomiting (5/20, 25%) and to
      avoid potential harm to the fetus (5/20, 25%). All side effects were mild and
      included gastrointestinal discomfort in a patient using elderberry, taste
      disturbance in a patient using echinacea, and intestinal gas in a patient using
      borage seed oil. Most patients informed their primary care provider of their use
      of dietary supplements (15/20, 75%). CONCLUSION: The use of dietary supplements
      among pregnant women is low but is of concern because of the lack of safety data.
      Most patients use dietary supplements to relieve gastrointestinal symptoms and
      disclose such use to their primary care provider.

PMID- 11518906
TI  - High prevalence of postpartum anemia among low-income women in the United States.
AB  - OBJECTIVE: To determine the prevalence of anemia from 4 to 26 weeks post partum
      and to examine prenatal predictors of postpartum anemia. STUDY DESIGN:
      Retrospective cohort analysis of 59,428 participants in the Special Supplemental
      Nutrition Program for Women, Infants, and Children in 12 US states. RESULTS: The
      prevalence of postpartum anemia was 27%. Anemia rates were higher among minority
      women, reaching 48% among non-Hispanic black women. Of 9129 women who had normal
      hemoglobin in the third trimester, 21% had postpartum anemia. Prenatal anemia was
      the strongest predictor of postpartum anemia (adjusted odds ratio, 2.7; 95%
      confidence interval, 2.5-2.8). Maternal obesity, multiple birth, and not breast
      feeding also predicted postpartum anemia. CONCLUSION: The high prevalence of post
      partum anemia among low-income women highlights the importance of anemia
      screening at 4 to 6 weeks post partum. These data suggest that screening should
      not be limited, as it is at present, to women considered at high risk.

PMID- 11518907
TI  - Episiotomy increases perineal laceration length in primiparous women.
AB  - OBJECTIVE: The aim of this study was to determine the clinical factors that
      contribute to posterior perineal laceration length. STUDY DESIGN: A prospective
      observational study was performed in 80 consenting, mostly primiparous women with
      term pregnancies. Posterior perineal lacerations were measured immediately after
      delivery. Numerous maternal, fetal, and operator variables were evaluated against
      laceration length and degree of tear. Univariate and multivariate regression
      analyses were performed to evaluate laceration length and parametric clinical
      variables. Nonparametric clinical variables were evaluated against laceration
      length by the Mann-Whitney U test. RESULTS: A multivariate stepwise linear
      regression equation revealed that episiotomy adds nearly 3 cm to perineal
      lacerations. Tear length was highly associated with the degree of tear (R = 0.86,
      R(2) = 0.73) and the risk of recognized anal sphincter disruption. None of 35
      patients without an episiotomy had a recognized anal sphincter disruption, but 6
      of 27 patients with an episiotomy did (P <.001). Body mass index was the only
      maternal or fetal variable that showed even a slight correlation with laceration
      length (R = 0.30, P =.04). CONCLUSION: Episiotomy is the overriding determinant
      of perineal laceration length and recognized anal sphincter disruption.

PMID- 11518908
TI  - High intake of energy, sucrose, and polyunsaturated fatty acids is associated
      with increased risk of preeclampsia.
AB  - OBJECTIVE: Preeclampsia is associated with high body mass index, insulin
      resistance, and hypertriglyceridemia. Our objective was to investigate
      prospectively whether diet in the first half of pregnancy is associated with the
      risk for preeclampsia. STUDY DESIGN: This prospective, population-based, cohort
      study of pregnant women investigated dietary intake early in the second trimester
      with a quantitative food frequency questionnaire. RESULTS: The questionnaire was
      completed by 3133 women (83%). Preeclampsia developed in 85 women. Adjusted odds
      ratio (95% CI) for preeclampsia was 3.7 (1.5-8.9) for energy intake of >3350
      kcal/d compared with < or =2000 kcal/d. Adjusted odds ratio (95% CI) for
      preeclampsia was 3.6 (1.3-9.8) for sucrose intake (percent of total energy) of
      >25% compared with < or =8.5% and 2.6 (1.3-5.4) for polyunsaturated fatty acids
      intake (percent of total energy) of >7.5% compared with < or =5.2%. Other energy
      providing nutrients were not associated with the risk for preeclampsia.
      CONCLUSION: The current study suggests that high intakes of energy, sucrose, and
      polyunsaturated fatty acids independently increase the risk for preeclampsia.

PMID- 11518909
TI  - Optimization of cytokine stability in stored amniotic fluid.
AB  - OBJECTIVE: Many studies use stored amniotic fluid samples to assay cytokines and
      other proteins for outcome-based research; however, there is little information
      on the optimal methods of storage. The objective of our study was to evaluate
      cytokine stability in amniotic fluid stored at different temperatures both with
      and without a proteolytic enzyme inhibitor. STUDY DESIGN: Patients undergoing
      midtrimester genetic amniocentesis for routine indications gave consent for the
      study. After the sample was centrifuged, the acellular portion of the sample was
      mixed to homogeneity and aliquoted in 0.5-mL increments and stored for 1 year at
      4 degrees C, -20 degrees C, and -80 degrees C with and without the protease
      inhibitor aprotinin. Enzyme-linked immunoassays for angiogenin, interleukin-6,
      and vascular endothelial growth factor were performed simultaneously on each
      aliquot. RESULTS: Thirty samples were assayed for each storage condition. Results
      were calculated as the percentage of its own sister aliquot stored at -80 degrees
      C without aprotinin. In all samples, there was a significant relation between
      storage temperature and cytokine levels, with the lowest levels found at 4
      degrees C and the highest at -80 degrees C (angiogenin, P =.004; interleukin-6, P
      <.001; vascular endothelial growth factor, P =.02). The addition of aprotinin
      improved stability only for angiogenin at all temperatures (all P <.05).
      CONCLUSIONS: Degradation of cytokines occurs when amniotic fluid samples are
      stored for prolonged periods at temperatures greater than -80 degrees C. The
      addition of a protease inhibitor helps stem the degradation of some cytokines.

PMID- 11518910
TI  - Impairment of growth in fetuses destined to deliver preterm.
AB  - OBJECTIVE: The objective of this study was to test the hypothesis that fetuses
      destined to deliver preterm do not reach their individual growth potential. STUDY
      DESIGN: In a case control design, data on 44 preterm deliveries at < or =34 weeks
      were compared with data on a control group of next consecutive term deliveries.
      Criteria for inclusion were dating by ultrasonography at <20 weeks and no medical
      or obstetric complications. For each fetus, GROW v.2 software was used to
      generate an individual optimal growth curve and to calculate the percentile of
      achieved growth potential for birth weight based on 6 independent factors
      (maternal weight, height, parity, ethnicity, fetal sex, and gestational age)
      identified as determining fetal weight from multivariate logistic regression
      analysis of 40,000 uncomplicated term pregnancies. Birth weight percentiles based
      on standard norms were also calculated for each fetus. RESULTS: The number of
      fetuses with birth weight below the 5th, 10th, and 25th percentile of their
      growth potential was significantly higher in the preterm group (10, 13, and 18)
      compared with that in the control group (2, 2, and 6; P <.008, P <.001, and P
      <.008, respectively). There were no significant differences in variables defining
      growth potential between the case and control groups. The number of fetuses below
      the 5th and 10th percentile based on standard birth weight norms was not
      significantly different between preterm and term pregnancies (3 vs 1 and 5 vs 2;
      P =.37 and P =.27). Among preterm deliveries, those preceded by preterm premature
      rupture of the membranes had significantly fewer fetuses >75th percentile of
      their growth potential (2 vs 8; P =.025). Fetuses with lower gestational ages at
      preterm delivery achieved lower median percentiles of their growth potential.
      CONCLUSION: A significant proportion of fetuses destined to deliver preterm do
      not reach their individual growth potential compared with those delivered at
      term. This finding challenges our concept of preterm delivery and management
      strategy aimed at tocolysis.

PMID- 11518911
TI  - Fetal serum concentrations of cystatin C and beta2-microglobulin as predictors of
      postnatal kidney function.
AB  - OBJECTIVES: Cystatin C and beta(2)-microglobulin are established serum markers of
      renal function in children and adults. In contrast to creatinine, diaplacental
      exchange is minimal. The aim of the study was to establish reference values in
      fetal serum and to test their efficiency in predicting postnatal kidney function.
      STUDY DESIGN: This was a prospective noninterventional study measuring cystatin C
      and beta(2)-microglobulin by particle-enhanced immunoturbidimetry in excess serum
      from 129 cordocenteses performed in 84 fetuses. Reference intervals (mean +/-
      1.96 SD) were calculated in a subgroup of 54 fetuses without evidence of kidney
      disease, and these reference values were evaluated in 75 sera from 55 fetuses.
      RESULTS: Mean cystatin C was 1.66 +/- 0.202 mg/L (upper limit 2.06), and mean
      beta(2)-microglobulin was 4.25 +/- 0.734 mg/L. Unlike cystatin C, beta(2)
      microglobulin decreased significantly with gestational age so that the upper
      reference limit was 7.19-0.052 x gestational age in weeks. beta(2)-Microglobulin
      had higher sensitivity (90.0% vs 63.6%) and cystatin C a higher specificity
      (91.8% vs. 85.5%) for the prediction of impaired renal function; diagnostic
      efficiency was equal (87.6% vs. 86.1%). Fetuses with impaired renal function at
      birth or who were aborted for renal malformations had higher cystatin C
      concentrations than those in a control group. beta(2)-Microglobulin was increased
      only in fetuses who were aborted. CONCLUSION: Fetal serum cystatin C and beta(2)
      microglobulin concentrations may be useful predictors of postnatal kidney
      function.

PMID- 11518912
TI  - A study of human leukocyte antigen G expression in hydatidiform moles.
AB  - OBJECTIVE: Human leukocyte antigen G (HLA-G) is a nonclassic major
      histocompatibility gene normally expressed only in extravillous trophoblasts
      throughout pregnancy. It may be responsible in part for the successful evasion of
      the hemiallogenic trophoblasts from maternal immune surveillance. We investigated
      whether HLA-G is expressed in molar pregnancies. STUDY DESIGN: We examined 5
      complete hydatidiform mole specimens and 5 partial hydatidiform mole specimens to
      determine whether HLA-G is expressed by immunohistochemistry and by RNA in situ
      hybridization analysis. RESULTS: We found that both the protein and RNA of HLA-G
      is expressed in complete and partial hydatidiform moles. CONCLUSION: HLA-G RNA
      and protein are expressed in molar pregnancies. HLA-G expression is independent
      of embryonic development and may therefore be an integral part of placental
      development. Furthermore, expression of HLA-G in the complete hydatidiform mole,
      a naturally occurring androgenote, confirms expression of the paternal allele of
      HLA-G. Imprinting of HLA-G is therefore unlikely to play a role in protecting
      fetal trophoblasts from maternal immune rejection.

PMID- 11518913
TI  - Management of isoimmunization in the presence of multiple maternal antibodies.
AB  - OBJECTIVE: Evaluation and management of patients with multiple maternal antibody
      isoimmunization is unclear. The presence of > or = 1 maternal antibody may
      suggest a worse scenario. The objective of this study was 2-fold: first, to
      determine whether the presence of multiple antibodies predicts a more severe
      course than single antibodies and second, to determine the utility of the Queenan
      curves/protocol in evaluating multiple-antibody isoimmunization. STUDY DESIGN:
      Amniotic fluid DeltaOD(450) measurements were obtained from the antenatal testing
      logbook and confirmed by chart review. Cases were categorized by antibody type
      and clinical outcomes obtained by chart review. RESULTS: Twenty-four pregnancies
      with isoimmunization and multiple maternal antibodies were identified; of these,
      17 had 2 antibodies (anti-D and -C in 13; anti-D and -E in 1; anti-D and -Jka in
      1; anti-c and -E in 1; and anti-c and -Jka in 1), and 7 had > 2 antibodies (anti
      D, -C, and -E in 4; anti-D, -C, and -N in 1; anti-c, -E, and -FYA in 1; and anti
      E, -K, -Fya, -S, and -C in 1). Eleven patients (46%) required at least 1
      intrauterine fetal transfusion (mean initial fetal hematocrit, 15%; range, 4.9%
      24%). In those not transfused, no DeltaOD(450) measurements occurred in the
      Queenan "fetal death risk" zone. Poorest outcomes (multiple
      transfusions/hydrops/fetal demise) were in patients with anti-D and anti-C, with
      or without anti-E. The absence of anti-D was associated with no need for fetal
      transfusions. The overall transfusion rate was significantly higher compared with
      a group of 57 isoimmunization patients with only anti-D (46% vs. 25%, P < or
      =.05). CONCLUSIONS: The presence of anti-D appears to be the most significant
      factor guiding the course of isoimmunization with multiple antibodies. The
      presence of another antibody with anti-D appears to significantly increase the
      need for intrauterine fetal transfusions. The Queenan protocol can successfully
      treat patients with multiple maternal red blood cell antibodies.

PMID- 11518914
TI  - Metronidazole treatment of women with a positive fetal fibronectin test result.
AB  - Eighty-nine women with either bacterial vaginosis, Trichomonas vaginalis, or
      both, who also had a positive fetal fibronectin test result were randomized to
      two courses of metronidazole treatment as part of a Maternal-Fetal Medicine
      Network Units study of the National Institute of Child Health and Human
      Development. In this subgroup analysis, compared with the placebo group, women
      who were treated with metronidazole had a nonsignificant reduction in spontaneous
      preterm birth from 14.6% to 8.3%.

PMID- 11518915
TI  - Effects of branched-chain amino acids on placental amino acid transfer and
      insulin and glucagon release in the ovine fetus.
AB  - OBJECTIVE: Competition for placental amino acid transporters can affect the fetal
      supply of amino acids. Specifically, the branched-chain amino acids-isoleucine,
      leucine, and valine-may inhibit the transfer of other amino acids. This study was
      undertaken to determine the effect of branched-chain amino acids on the umbilical
      uptake of amino acids. STUDY DESIGN: Six late-gestation ewes were infused
      sequentially for 2 hours with 3 different mixtures of amino acids: (1) one that
      was comparable to commercial parenteral nutrition preparations, (2) the same
      solution without branched-chain amino acids, and (3) branched-chain amino acids
      alone. Maternal and fetal blood samples were collected simultaneously for the
      determination of uterine and umbilical uptake values of amino acids, and for
      concentrations of arterial insulin, glucagon, glucose, and lactate before
      (control) and during (experimental) infusion. RESULTS: Umbilical uptake of
      branched-chain amino acids increased significantly when they were present in the
      infusates. The fetal uptake of several other amino acids could be increased by
      increasing their maternal concentrations. Inhibition of umbilical uptake by
      branched-chain amino acids could be shown for threonine and methionine. The
      infusion of branched-chain amino acids alone did not affect maternal and fetal
      insulin or glucagon concentrations. CONCLUSIONS: In late-gestation sheep, an
      increase in maternal plasma concentration of branched-chain amino acids led to
      increased branched-chain amino acid umbilical uptake, but branched-chain amino
      acids can also inhibit the transport of some amino acids to the fetus. Changes in
      fetal plasma concentration and uptake of branched-chain amino acid appear to have
      no significant effect on fetal insulin or glucagon.

PMID- 11518916
TI  - Umbilical arteritis and phlebitis mark different stages of the fetal inflammatory
      response.
AB  - OBJECTIVE: Funisitis, the inflammation of the umbilical cord determined by
      histologic examination of the placenta, is evidence of a fetal inflammatory
      response. The inflammatory process may involve the umbilical vein (phlebitis) and
      one or both umbilical arteries (arteritis) and extend into the Wharton's jelly.
      This study was conducted to examine whether the pattern of inflammation of the
      umbilical cord correlates with a biochemical marker of systemic fetal
      inflammation (umbilical cord plasma interleukin-6) and an adverse neonatal
      outcome. STUDY DESIGN: This cohort study included 636 cases of preterm delivery
      (<36 weeks) with or without inflammation of the umbilical cord. Umbilical cord
      blood was collected at the time of delivery. The aim of pathologic examination
      was to characterize the extent of umbilical cord inflammation and the involvement
      of the vein (phlebitis), the involvement of one or both arteries (arteritis), and
      the presence of inflammation of the Wharton's jelly. Umbilical cord plasma
      interleukin-6 concentrations were assayed by a sensitive and specific
      immunoassay. RESULTS: Neonates with umbilical arteritis had a significantly
      higher median concentration of cord plasma interleukin-6 (median, 111 pg/mL;
      range, 0.1-19,230 pg/mL) than those without umbilical arteritis (median, 22.5
      pg/mL; range, 0.9-511.6 pg/mL; P <.05). Also, severe neonatal morbidity occurred
      more frequently in infants with arteritis than in those without arteritis (74% vs
      50%; P <.05). And finally, the most severe form of inflammation, which involves
      both arteries, vein, and Wharton's jelly, was associated with the highest median
      concentration of plasma interleukin-6 observed in this study (median, 182.6
      pg/mL; range, 0.1-7,400 pg/mL), whereas inflammation limited to the vein
      (phlebitis) was associated with a lower concentration of cord plasma interleukin
      6 (median, 29.1 pg/mL; range, 0.9-511.6 pg/mL; P <.05). CONCLUSION: Neonates
      whose placenta demonstrates umbilical arteritis have higher concentrations of
      umbilical cord plasma interleukin-6 and higher rates of adverse outcome than
      those without umbilical arteritis.

PMID- 11518917
TI  - Erythrocyte and erythropoietin responses to hemorrhage in the immature and near
      term ovine fetus.
AB  - OBJECTIVE: Previous reports suggested that immature ovine fetuses have a greater
      erythropoietin response to hemorrhage than those near term. This study tested the
      hypothesis that immature ovine fetuses would expand their red cell mass more
      rapidly than near term fetuses after hemorrhage. STUDY DESIGN: Chronically
      catheterized immature ovine fetuses at 109.5 +/- 0.3 (mean +/- SE) days'
      gestation (term = 150 days) were studied over a 10-day period. They either
      underwent hemorrhage of 40% of their measured blood volume on day 3 or were in a
      time control group monitored without hemorrhage. Red cell mass, hematocrit, blood
      volume, plasma volume, and plasma erythropoietin concentrations were measured at
      24- and 48-hour intervals. Responses in the immature fetuses were compared with
      responses in near term fetuses. RESULTS: In the control group red cell mass,
      hematocrit, blood, and plasma volumes increased significantly, whereas plasma
      erythropoietin concentration decreased significantly with advancing gestational
      age. In immature fetuses that underwent hemorrhage, the relative changes in red
      cell mass, hematocrit, and plasma erythropoietin concentration were not
      significantly different from those seen in the near term fetuses. The only
      significant posthemorrhage difference was that the increases in blood and plasma
      volumes were greater in the immature compared with the near term fetuses.
      CONCLUSION: Immature and mature fetuses have similar erythrocyte and
      erythropoietin responses to moderately severe hemorrhage. The larger blood and
      plasma volume responses in the immature fetuses are consistent with the concept
      that they have a greater extracellular fluid volume.

PMID- 11518918
TI  - Residency training in colposcopy: a survey of program directors in obstetrics and
      gynecology and family practice.
AB  - OBJECTIVE: Our goal was to identify how colposcopy is being taught to residents
      in obstetrics and gynecology and family practice programs and to see if the
      program directors think their residents receive sufficient clinical exposure to
      be adequately trained in colposcopy. STUDY DESIGN: A 30-question survey was sent
      to all obstetrics and gynecology and family practice residency program directors.
      The survey included questions about the didactic nature of the colposcopy
      curriculum, the type of supervision, how resident skills are evaluated, estimates
      of the numbers and types of patients evaluated, the numbers and types of
      procedures being done by each resident, and the program director's perception of
      residents' competence in colposcopy. RESULTS: The overall response rate was 485
      of 752 program directors (64.5%). Significantly fewer family practice than
      obstetrics and gynecology program directors thought they had adequate numbers of
      colposcopy patients to train their residents. By their program directors'
      estimates, 86% of family practice residents evaluate 10 or fewer patients with
      high-grade lesions (versus 16.5% of obstetrics and gynecology residents); 51.4%
      evaluate 10 patients or fewer with low-grade lesions (versus 6.7% of obstetrics
      and gynecology residents), and 40.6% evaluate 10 patients or fewer with atypical
      squamous cells of undetermined significance (versus 3% of obstetrics and
      gynecology residents). Experience with vulvar disease is also limited. Program
      directors thought their residents' colposcopy skills were roughly comparable with
      their general obstetrics and gynecology skills. CONCLUSIONS: It is possible that
      many program directors underestimate the number of colposcopic examinations
      required to achieve and maintain colposcopic skills. Many training programs have
      insufficient clinical volume to properly train residents in colposcopy.

PMID- 11518919
TI  - Nocturia in women.
AB  - Frequent episodes of nocturnal voiding disturb the sleep and well-being of women.
      The prevalence of nocturia is more common in parous women and shows a linear
      increase with age, occurring in more than 50% of women > or =80 years old.
      Nocturia has a multifactorial origin that develops through a pathophysiologic
      mechanism of nocturnal polyuria or low functional bladder capacity or through a
      combination of both. Nocturia is also one of the most bothersome lower urinary
      tract symptoms and has a significant impact on quality of life. However, most
      women accept symptoms of nocturia as part of the aging process and few seek
      medical help. Treatments for nocturia (behavior modification and pharmacologic
      treatment) are effective in many cases, although it is important to tailor
      treatment to the underlying pathophysiology. This review discusses the impact of
      nocturia on women and reviews the current situation regarding the definition,
      prevalence, diagnosis, and treatment of this condition in this patient
      population.

PMID- 11518920
TI  - Cornual heterotopic pregnancy: contemporary management options.

PMID- 11518921
TI  - Doppler velocimetry: is it useful in preeclampsia?

PMID- 11518922
TI  - Neurobiology of maternal asthma and pregnancy outcomes.

PMID- 11518923
TI  - Aspirin to treat obstetric manifestations of the antiphospholipid syndrome.

PMID- 11518924
TI  - Declaration of financial interests.

PMID- 11518925
TI  - Stem-cell giveaway proposed as confusion reigns over cell count.

PMID- 11518927
TI  - Riders on the storm provoke studies of Atlantic dust.

PMID- 11518926
TI  - Partners turn to court over stem-cell rights.

PMID- 11518928
TI  - Japan banks on tissue store for successful drugs.

PMID- 11518929
TI  - German centre set to improve brain's image.

PMID- 11518930
TI  - Ecologists plot to turn the tide for shrinking lake.

PMID- 11518932
TI  - Staff suggest cure for Smithsonian woes.

PMID- 11518931
TI  - Code-breakers reveal results as threat of legal action is lifted.

PMID- 11518935
TI  - The battlefields of Britain.

PMID- 11518936
TI  - The positron probe.

PMID- 11518937
TI  - How commercialization puts a blight on research.

PMID- 11518938
TI  - Biotechnology gets big backing in Australia.

PMID- 11518944
TI  - Yes, but what's it for?

PMID- 11518945
TI  - Delicate information.

PMID- 11518946
TI  - Fast track to fusion energy.

PMID- 11518947
TI  - Neurobiology: The many faces of adaptation.

PMID- 11518948
TI  - Earth science: Journey beneath southern Africa.

PMID- 11518950
TI  - Developmental biology: clocks and hox.

PMID- 11518951
TI  - Planetary science: Gases make a rare appearance.

PMID- 11518952
TI  - Optics: Armed for light sensing.

PMID- 11518954
TI  - Export of organic carbon from peat soils.

PMID- 11518955
TI  - Resource availability: Ancient homes for hard-up hermit crabs.
AB  - Mollusc shells are a vital but sometimes scarce resource for hermit crabs,
      protecting them from mechanical damage and desiccation, but they require
      continual replacement as the crab grows. I have discovered that Coenobita
      rugosus, a large, tropical, semi-terrestrial hermit crab, will resort to using
      fossil shells when no other suitable casing is available. These unlikely mobile
      homes fall out of coastal limestone as it is eroded by the sea in southwestern
      Madagascar, placing the occupants alongside Homo sapiens as resourceful
      exploiters of prehistoric animal remains.

PMID- 11518957
TI  - Efficiency and ambiguity in an adaptive neural code.
AB  - We examine the dynamics of a neural code in the context of stimuli whose
      statistical properties are themselves evolving dynamically. Adaptation to these
      statistics occurs over a wide range of timescales-from tens of milliseconds to
      minutes. Rapid components of adaptation serve to optimize the information that
      action potentials carry about rapid stimulus variations within the local
      statistical ensemble, while changes in the rate and statistics of action
      potential firing encode information about the ensemble itself, thus resolving
      potential ambiguities. The speed with which information is optimized and
      ambiguities are resolved approaches the physical limit imposed by statistical
      sampling and noise.

PMID- 11518958
TI  - Discovery of three lead-rich stars.
AB  - About half of the stable nuclei heavier than iron are believed to be synthesized
      during the late stages of evolution of stars with masses in the range 0.8-8 solar
      masses. These elements are then expelled into the interstellar medium through
      stellar winds after being 'dredged up' towards the surface of the stars. These
      processes occur when the star is in the 'asymptotic giant branch' (AGB) phase of
      its life. Nuclei (mainly iron) deep inside the star slowly capture neutrons and
      progressively build up heavier elements (the 's-process'). For AGB stars that
      formed early in the history of the Galaxy, and that therefore have very low
      abundances of elements heavier than helium ('metals'), models predict that the s
      process will accumulate synthesized material with atomic weights in the Pb-Bi
      region. Such stars will therefore have large overabundances of lead relative to
      other heavy elements. Here we report the discovery of large amounts of lead in
      three metal-poor stars (HD187861, HD196944 and HD224959). Our analysis shows that
      these stars are more enriched in lead than in any other element heavier than
      iron. The excellent agreement between the observed and predicted abundances
      reinforces our current understanding of the detailed operation of the s-process
      deep in the interiors of AGB stars.

PMID- 11518959
TI  - Noble-gas-rich chondrules in an enstatite meteorite.
AB  - Chondrules are silicate spherules that are found in abundance in the most
      primitive class of meteorites, the chondrites. Chondrules are believed to have
      formed by rapid cooling of silicate melt early in the history of the Solar
      System, and their properties should reflect the composition of (and physical
      conditions in) the solar nebula at the time when the Sun and planets were
      forming. It is usually believed that chondrules lost all their noble gases at the
      time of melting. Here we report the discovery of significant amounts of trapped
      noble gases in chondrules in the enstatite chondrite Yamato-791790, which
      consists of highly reduced minerals. The elemental ratios 36Ar/132Xe and
      84Kr/132Xe are similar to those of 'subsolar' gas, which has the highest
      36Ar/132Xe ratio after that of solar-type noble gases. The most plausible
      explanation for the high noble-gas concentration and the characteristic elemental
      ratios is that solar gases were implanted into the chondrule precursor material,
      followed by incomplete loss of the implanted gases through diffusion over time.

PMID- 11518960
TI  - Fast heating of ultrahigh-density plasma as a step towards laser fusion ignition.
AB  - Modern high-power lasers can generate extreme states of matter that are relevant
      to astrophysics, equation-of-state studies and fusion energy research. Laser
      driven implosions of spherical polymer shells have, for example, achieved an
      increase in density of 1,000 times relative to the solid state. These densities
      are large enough to enable controlled fusion, but to achieve energy gain a small
      volume of compressed fuel (known as the 'spark') must be heated to temperatures
      of about 108 K (corresponding to thermal energies in excess of 10 keV). In the
      conventional approach to controlled fusion, the spark is both produced and heated
      by accurately timed shock waves, but this process requires both precise implosion
      symmetry and a very large drive energy. In principle, these requirements can be
      significantly relaxed by performing the compression and fast heating separately;
      however, this 'fast ignitor' approach also suffers drawbacks, such as propagation
      losses and deflection of the ultra-intense laser pulse by the plasma surrounding
      the compressed fuel. Here we employ a new compression geometry that eliminates
      these problems; we combine production of compressed matter in a laser-driven
      implosion with picosecond-fast heating by a laser pulse timed to coincide with
      the peak compression. Our approach therefore permits efficient compression and
      heating to be carried out simultaneously, providing a route to efficient fusion
      energy production.

PMID- 11518961
TI  - Formation of ordered ice nanotubes inside carbon nanotubes.
AB  - Following their discovery, carbon nanotubes have attracted interest not only for
      their unusual electrical and mechanical properties, but also because their hollow
      interior can serve as a nanometre-sized capillary, mould or template in material
      fabrication. The ability to encapsulate a material in a nanotube also offers new
      possibilities for investigating dimensionally confined phase transitions.
      Particularly intriguing is the conjecture that matter within the narrow confines
      of a carbon nanotube might exhibit a solid-liquid critical point beyond which the
      distinction between solid and liquid phases disappears. This unusual feature,
      which cannot occur in bulk material, would allow for the direct and continuous
      transformation of liquid matter into a solid. Here we report simulations of the
      behaviour of water encapsulated in carbon nanotubes that suggest the existence of
      a variety of new ice phases not seen in bulk ice, and of a solid-liquid critical
      point. Using carbon nanotubes with diameters ranging from 1.1 nm to 1.4 nm and
      applied axial pressures of 50 MPa to 500 MPa, we find that water can exhibit a
      first-order freezing transition to hexagonal and heptagonal ice nanotubes, and a
      continuous phase transformation into solid-like square or pentagonal ice
      nanotubes.

PMID- 11518962
TI  - Efficient silicon light-emitting diodes.
AB  - Considerable effort is being expended on the development of efficient silicon
      light-emitting devices compatible with silicon-based integrated circuit
      technology. Although several approaches are being explored, all presently suffer
      from low emission efficiencies, with values in the 0.01-0.1% range regarded as
      high. Here we report a large increase in silicon light-emitting diode power
      conversion efficiency to values above 1% near room temperature-close to the
      values of representative direct bandgap emitters of a little more than a decade
      ago. Our devices are based on normally weak one- and two-phonon assisted sub
      bandgap light-emission processes. Their design takes advantage of the reciprocity
      between light absorption and emission by maximizing absorption at relevant sub
      bandgap wavelengths while reducing the scope for parasitic non-radiative
      recombination within the diode. Each feature individually is shown to improve the
      emission efficiency by a factor of ten, which accounts for the improvement by a
      factor of one hundred on the efficiency of baseline devices.

PMID- 11518963
TI  - Intensified deep Pacific inflow and ventilation in Pleistocene glacial times.
AB  - The production of cold, deep waters in the Southern Ocean is an important factor
      in the Earth's heat budget. The supply of deep water to the Pacific Ocean is
      presently dominated by a single source, the deep western boundary current east of
      New Zealand. Here we use sediment records deposited under the influence of this
      deep western boundary current to reconstruct deep-water properties and speed
      changes during the Pleistocene epoch. In physical and isotope proxies we find
      evidence for intensified deep Pacific Ocean inflow and ventilation during the
      glacial periods of the past 1.2 million years. The changes in throughflow may be
      directly related to an increased production of Antarctic Bottom Water during
      glacial times. Possible causes for such an increased bottom-water production
      include increasing wind strengths in the Southern Ocean or an increase in annual
      sea-ice formation, leaving dense water after brine rejection and thereby
      enhancing deep convection. We infer also that the global thermohaline circulation
      was perturbed significantly during the mid-Pleistocene climate transition between
      0.86 and 0.45 million years ago.

PMID- 11518964
TI  - Tectonic contraction across Los Angeles after removal of groundwater pumping
      effects.
AB  - After the 1987 Whittier Narrows and 1994 Northridge earthquakes revealed that
      blind thrust faults represent a significant threat to metropolitan Los Angeles, a
      network of 250 continuously recording global positioning system (GPS) stations
      was deployed to monitor displacements associated with deep slip on both blind and
      surface faults. Here we augment this GPS data with interferometric synthetic
      aperture radar imagery to take into account the deformation associated with
      groundwater pumping and strike-slip faulting. After removing these non-tectonic
      signals, we are left with 4.4 mm yr-1 of uniaxial contraction across the Los
      Angeles basin, oriented N 36 degrees E (perpendicular to the major strike-slip
      faults in the area). This indicates that the contraction is primarily
      accommodated on thrust faults rather than on the northeast-trending strike-slip
      faults. We have found that widespread groundwater and oil pumping obscures and in
      some cases mimics the tectonic signals expected from the blind thrust faults. In
      the 40-km-long Santa Ana basin, groundwater withdrawal and re-injection produces
      12 mm yr-1 of long-term subsidence, accompanied by an unprecedented seasonal
      oscillation of 55 mm in the vertical direction and 7 mm horizontally.

PMID- 11518965
TI  - Evidence of intra-specific competition for food in a pelagic seabird.
AB  - The factors affecting the population dynamics of seabirds have long intrigued
      biologists. Current data suggest that density-dependent depletion of prey during
      the breeding season may regulate population size. However, much of the evidence
      for this has been circumstantial, and the underlying mechanisms are unclear.
      Here, we show that the per capita population growth rates of northern gannet
      Morus bassanus at colonies in Britain and Ireland have declined with increasing
      population size. Furthermore, direct observations reveal that the mean foraging
      trip duration of breeding gannets is positively correlated with colony size, both
      among colonies of different sizes in the same year, and within colonies as they
      change in size. To understand this phenomenon, we have developed a model which
      demonstrates that disturbance of fish alone can readily generate conditions under
      which gannets at larger colonies have to travel further to obtain food.

PMID- 11518966
TI  - Calcitic microlenses as part of the photoreceptor system in brittlestars.
AB  - Photosensitivity in most echinoderms has been attributed to 'diffuse' dermal
      receptors. Here we report that certain single calcite crystals used by
      brittlestars for skeletal construction are also a component of specialized
      photosensory organs, conceivably with the function of a compound eye. The
      analysis of arm ossicles in Ophiocoma showed that in light-sensitive species, the
      periphery of the labyrinthic calcitic skeleton extends into a regular array of
      spherical microstructures that have a characteristic double-lens design. These
      structures are absent in light-indifferent species. Photolithographic experiments
      in which a photoresist film was illuminated through the lens array showed
      selective exposure of the photoresist under the lens centres. These results
      provide experimental evidence that the microlenses are optical elements that
      guide and focus the light inside the tissue. The estimated focal distance (4-7
      micrometer below the lenses) coincides with the location of nerve bundles-the
      presumed primary photoreceptors. The lens array is designed to minimize spherical
      aberration and birefringence and to detect light from a particular direction. The
      optical performance is further optimized by phototropic chromatophores that
      regulate the dose of illumination reaching the receptors. These structures
      represent an example of a multifunctional biomaterial that fulfills both
      mechanical and optical functions.

PMID- 11518967
TI  - Delineation of prognostic biomarkers in prostate cancer.
AB  - Prostate cancer is the most frequently diagnosed cancer in American men.
      Screening for prostate-specific antigen (PSA) has led to earlier detection of
      prostate cancer, but elevated serum PSA levels may be present in non-malignant
      conditions such as benign prostatic hyperlasia (BPH). Characterization of gene
      expression profiles that molecularly distinguish prostatic neoplasms may identify
      genes involved in prostate carcinogenesis, elucidate clinical biomarkers, and
      lead to an improved classification of prostate cancer. Using microarrays of
      complementary DNA, we examined gene-expression profiles of more than 50 normal
      and neoplastic prostate specimens and three common prostate-cancer cell lines.
      Signature expression profiles of normal adjacent prostate (NAP), BPH, localized
      prostate cancer, and metastatic, hormone-refractory prostate cancer were
      determined. Here we establish many associations between genes and prostate
      cancer. We assessed two of these genes-hepsin, a transmembrane serine protease,
      and pim-1, a serine/threonine kinase-at the protein level using tissue
      microarrays consisting of over 700 clinically stratified prostate-cancer
      specimens. Expression of hepsin and pim-1 proteins was significantly correlated
      with measures of clinical outcome. Thus, the integration of cDNA microarray, high
      density tissue microarray, and linked clinical and pathology data is a powerful
      approach to molecular profiling of human cancer.

PMID- 11518968
TI  - Haematopoietic cell-specific CDM family protein DOCK2 is essential for lymphocyte
      migration.
AB  - Cell migration is a fundamental biological process involving membrane
      polarization and cytoskeletal dynamics, both of which are regulated by Rho family
      GTPases. Among these molecules, Rac is crucial for generating the actin-rich
      lamellipodial protrusion, a principal part of the driving force for movement. The
      CDM family proteins, Caenorhabditis elegans CED-5, human DOCK180 and Drosophila
      melanogaster Myoblast City (MBC), are implicated to mediate membrane extension by
      functioning upstream of Rac. Although genetic analysis has shown that CED-5 and
      Myoblast City are crucial for migration of particular types of cells,
      physiological relevance of the CDM family proteins in mammals remains unknown.
      Here we show that DOCK2, a haematopoietic cell-specific CDM family protein, is
      indispensable for lymphocyte chemotaxis. DOCK2-deficient mice (DOCK2-/-)
      exhibited migration defects of T and B lymphocytes, but not of monocytes, in
      response to chemokines, resulting in several abnormalities including T
      lymphocytopenia, atrophy of lymphoid follicles and loss of marginal-zone B cells.
      In DOCK2-/- lymphocytes, chemokine-induced Rac activation and actin
      polymerization were almost totally abolished. Thus, in lymphocyte migration DOCK2
      functions as a central regulator that mediates cytoskeletal reorganization
      through Rac activation.

PMID- 11518969
TI  - The core of the motor domain determines the direction of myosin movement.
AB  - Myosins constitute a superfamily of at least 18 known classes of molecular motors
      that move along actin filaments. Myosins move towards the plus end of F-actin
      filaments; however, it was shown recently that a certain class of myosin, class
      VI myosin, moves towards the opposite end of F-actin, that is, in the minus
      direction. As there is a large, unique insertion in the myosin VI head domain
      between the motor domain and the light-chain-binding domain (the lever arm), it
      was thought that this insertion alters the angle of the lever-arm switch
      movement, thereby changing the direction of motility. Here we determine the
      direction of motility of chimaeric myosins that comprise the motor domain and the
      lever-arm domain (containing an insert) from myosins that have movement in the
      opposite direction. The results show that the motor core domain, but neither the
      large insert nor the converter domain, determines the direction of myosin
      motility.

PMID- 11518971
TI  - Try the soft option.

PMID- 11518970
TI  - Catalysis by hen egg-white lysozyme proceeds via a covalent intermediate.
AB  - Hen egg-white lysozyme (HEWL) was the first enzyme to have its three-dimensional
      structure determined by X-ray diffraction techniques. A catalytic mechanism,
      featuring a long-lived oxocarbenium-ion intermediate, was proposed on the basis
      of model-building studies. The 'Phillips' mechanism is widely held as the
      paradigm for the catalytic mechanism of beta-glycosidases that cleave glycosidic
      linkages with net retention of configuration of the anomeric centre. Studies with
      other retaining beta-glycosidases, however, provide strong evidence pointing to a
      common mechanism for these enzymes that involves a covalent glycosyl-enzyme
      intermediate, as previously postulated. Here we show, in three different cases
      using electrospray ionization mass spectrometry, a catalytically competent
      covalent glycosyl-enzyme intermediate during the catalytic cycle of HEWL. We also
      show the three-dimensional structure of this intermediate as determined by X-ray
      diffraction. We formulate a general catalytic mechanism for all retaining beta
      glycosidases that includes substrate distortion, formation of a covalent
      intermediate, and the electrophilic migration of C1 along the reaction
      coordinate.

PMID- 11518972
TI  - Endoscopic forehead lifting and contouring.
AB  - The concept of endoscopic foreheadplasty is based upon a sub- or supraperiosteal
      dissection of the parietal, occipital and frontal scalp, incision and release of
      the superior and lateral orbital periosteum, selective myotomies of the brow
      depressor muscles, and brow elevation into a desired position with fixation and
      healing. A significant limitation of this procedure appears to be the ability to
      predict the long-term forehead and brow elevation. We review the anatomy relevant
      to forehead rejuvenation surgery and present our surgical technique for permanent
      fixation endoscopic forehead lifting. We discuss the scientific rationale for
      permanent fixation to ensure long-term forehead and brow position and draw our
      conclusions based upon the results of animal and clinical studies that have been
      completed.

PMID- 11518973
TI  - Botulinum A exotoxin for rejuvenation of the upper third of the face.
AB  - Botulinum A exotoxin, derived from the gram-positive anaerobe Clostridium
      botulinum, has proven to be safe and effective in the temporary treatment of
      facial rhytides. In order to obtain reproducible results and avoid complications,
      it is necessary to understand the relevant physiology and anatomic relationships.
      Technical considerations including injection technique, dilution, storage, and
      potential complications will be discussed.

PMID- 11518974
TI  - Transconjunctival versus transcutaneous approach in upper and lower
      blepharoplasty.
AB  - In this article, we review the traditional transcutaneous upper lid
      blepharoplasty technique and contrast it to the newly described transconjunctival
      upper lid blepharoplasty technique that has limited indications. The technique
      and application of the skin-muscle flap transcutaneous lower lid blepharoplasty
      and the transconjunctival lower lid blepharoplasty are also discussed. We prefer
      the transconjunctival lower lid blepharoplasty as it circumvents the risk of
      lower eyelid retraction associated with the transcutaneous approach. We also
      discuss application of adjunctive procedures to the transconjunctival approach to
      enhance cosmetic results.

PMID- 11518975
TI  - The multivectorial subperiosteal midface lift.
AB  - Traditional rejuvenation on the midface has been predicated on extension of
      laterally based rhytidectomy techniques. Recently, attempts to improve this area
      have been performed through brow access points and are directed superolaterally.
      Transblepharoplasty approaches have in the past focused on limited rejuvenation
      of the immediate periocular area. The technique described in this article is a
      method by which the multiple directions of midfacial aging can be reversed and
      corrected with greater safety and better visualization than previously described.

PMID- 11518976
TI  - SOOF lift and lateral retinacular canthoplasty.
AB  - Eyelid rejuvenation surgery may be slowly shifting from pure fat removal
      techniques to those that preserve and reposition the periorbital fat. The
      traditional subciliary incision blepharoplasty was fraught with minor and major
      complications, and while the transconjunctival blepharoplasty afforded lower
      morbidity, its inability to address all aspects of periorbital rejuvenation
      eventually limited its popularity. Coincidentally, a search by aesthetic surgeons
      was on for better techniques to lift the midface, soften the nasolabial fold, and
      efface the tear trough deformity. In an effort to avoid the lid malposition
      complications that often accompany transblepharoplasty cheek lifting, innovative
      canthoplasty and canthopexy techniques were developed, which paved the way for a
      safe return to subciliary blepharoplasty surgery. Effacement of the tear trough
      deformity, now considered to be a major determinant in successful periorbital
      rejuvenation, could be achieved through fat repositioning and without the use of
      alloplastic implants or free fat grafts, thus improving reliability while
      minimizing complications. By preserving periorbital fat the hollowed out orbit,
      often seen after traditional blepharoplasty, could be avoided. The technique
      described in this article is a composite of several previously published
      approaches, is simple for the experienced blepharoplasty surgeon to master, and
      has been used with safety and reliability over the past 18 months in the senior
      author's practice.

PMID- 11518977
TI  - Midfacial effects of the deep-plane facelift.
AB  - Rejuvenation of the midface is a challenge in facial plastic surgery. To this
      end, several techniques have been developed to address the changes seen in the
      midface with aging. Specifically, ptosis of the malar fat pad and deepening of
      the nasolabial fold contribute to the aesthetic changes that characterize
      midfacial aging. The history of modern facelifts and deep-plane facelift
      techniques to correct the nasolabial fold are presented.

PMID- 11518978
TI  - Temporal facelift and corrugator resection.
AB  - On a path analogous to other surgical disciplines, the progression of facial
      cosmetic surgery has trended toward shorter scars and less invasive techniques.
      This article outlines an approach to facelifting that limits the scar to the
      temporal scalp, preauricular area, and retroauricular sulcus. It will enable the
      reader to identify those patients who are candidates for a less invasive
      procedure compared with the conventional facelift approach. Specifically, the
      temporal facelift addresses the lateral brow, the middle one third of the face,
      and the upper neck. In addition, this article examines the various and current
      methods for treatment of the glabellar area of the forehead. Medical and surgical
      options are outlined for the correction of those rhytids induced by corrugator
      and procerus muscle activity.

PMID- 11518979
TI  - Augmentation of the cheeks, chin and pre-jowl sulcus, and nasolabial folds.
AB  - The demand for augmentation of central and lower facial features continues to
      increase. There are several safe and effective materials available for this
      purpose, and techniques have become highly refined. The relative strengths and
      weaknesses of silicone, expanded polytetrafluoroethylene (ePTFE), high-density
      polyethylene (HDPE), and merseline mesh are discussed for augmentation of the
      chin/pre-jowl sulcus and cheek. Materials for augmentation of the nasolabial
      folds (NLF) are also discussed. There are various forms of solid ePTFE that have
      been developed for soft tissue augmentation. These are particularly well suited
      for the NLF. Techniques for facial skeletal and soft tissue augmentation are
      presented.

PMID- 11518980
TI  - Collagen, human collagen, and fat: the search for a three-dimensional soft tissue
      filler.
AB  - As the body ages, not only are the soft tissues of the face subject to gravity
      but they also may undergo progressive atrophy. Suspensory procedures may return
      the tissues to a more youthful position, but the atrophic changes are left
      uncorrected and produce an aged appearance. Three-dimensional (3-D) soft tissue
      fillers ideally would replace the bulk that was lost. Safety, persistence, and
      verisimilitude to the native tissues should be optimal in useful 3-D fillers. To
      date, no such material has been described, but there has been a resurgence in
      natural materials for this purpose. This article serves as an update on human
      derived soft tissue fillers.

PMID- 11518981
TI  - [Carpal injuries associated with distal radius fractures. Diagnosis and therapy].
AB  - The frequency of carpal injuries associated with distal radius fractures is often
      underestimated. Diagnosis of such lesions can be difficult. Important diagnostic
      steps include conventional X-rays, cinematography of the wrist, MRI, and
      arthroscopy. Different procedures such as wrist arthrography and CT are of
      secondary value. An early diagnosis of ligament injuries and instabilities can be
      obtained through cinematographic examination, whereas injuries to the TFCC are
      mainly diagnosed by MRI. Arthroscopy provides exact diagnosis as well as therapy,
      including arthroscopically controlled reposition of centrally depressed fragments
      of the articular surface of the radius and even treatment of TFCC lesions.

PMID- 11518982
TI  - [Arthroscopic diagnosis of concomitant scapholunate ligament injuries in
      fractures of the distal radius].
AB  - To investigate the occurrence of carpal ligamentous injuries in patients with
      fractures of the distal radius, the results of 122 wrist arthroscopies were
      analysed within a retrospective study. Indications for arthroscopy included
      suspected carpal instability according to radiographic findings and/or the
      necessity for internal fixation of the radius fracture. Arthroscopy revealed
      acute scapholunate ligament tears in 84 patients. Scapholunate separation was
      found to be of prognostic value for ligament tears. There was no association
      between ligamentous lesions and carpal angles or fracture dislocation.
      Scapholunate ligament tears were most frequent in sagittal articular fractures.
      In these cases, wrist arthroscopy should be performed during operative treatment
      of the radius fracture to allow direct visualization and subsequent repair of
      ligamentous tears.

PMID- 11518983
TI  - [MRI or arthroscopy in the diagnosis of scapholunate ligament tears in fractures
      of the distal radius?].
AB  - In a prospective study, 45 patients with fractures of the distal radius and
      radiologically suspected tears of the scapholunate interosseous ligament were
      examined. Magnetic resonance imaging was performed prior to wrist arthroscopy.
      The latter examination gave the definite diagnosis. MRI was performed in
      conventional technique (without contrast medium) in 25 cases and after additional
      intravenous injection of contrast medium in the remaining 20 patients. The images
      were obtained with a 1.0-T clinical imager using a T(2)-weighted turbo spin echo
      sequence (slice 3 mm, transversal) and a FLASH 2D sequence (slice 2 mm,
      oblique/coronal). Three independent observers assessed the MRI scans before
      arthroscopy was performed. The correct diagnosis was made by MRI in 76 %. Overall
      sensitivity and specificity came to 71 % and 86 %, respectively. The use of
      intravenously applied contrast medium did not improve MRI accuracy. In
      conclusion, MRI is not recommended for the diagnosis of scapholunate ligament
      tears. Presumably, the results of MRI could be improved by a more sophisticated
      technique.

PMID- 11518984
TI  - [What are the indications for arthroscopic repair of ulnar tears of the TFCC?].
AB  - A clinical study was performed to assess the outcome after arthroscopic repair of
      ulnar tears of the TFCC of the wrist, and to determine which factors are of
      importance for the results. From 1994 until 1998, in 23 patients an ulnar tear of
      the TFCC of the wrist was found and treated by arthroscopic repair (average age
      32 years, range 16 to 56, 11 female, 12 male). The articular disc was sutured by
      inside-outside-technique with 2/0 PDS to the floor of the sixth extensor
      compartment. 14 to 54 months (mean 27 months) after the operation, 21 patients
      were reexamined. The results were graded according to the Mayo-modified wrist
      score. Several factors which might be of influence were correlated to the results
      by crosstabs including preoperative clinical assessment of stability of the
      distal radioulnar joint (DRUJ), time between trauma and repair, mechanism of
      injury, associated lesions, details of suturing technique, and the amount of
      loading of the wrist in daily life. In nine patients, the result was rated as
      excellent, in five patients good, in four patients fair, and in three patients
      poor. The average preoperative score was 55.7 points, the average postoperative
      score was 84 points. The difference was statistically significant as calculated
      by the paired sample t-test (p < 0.05). In preoperative clinical examinations, 13
      DRUJs had been assessed as stable, eight as unstable. In the crosstabulation, a
      significant correlation was found between excellent results and preoperatively
      preserved stability of the DRUJ, whereas fair and poor results have often been
      found with clinically unstable DRUJ. The other factors revealed no correlations
      with the results. Ulnar tears of the TFCC of the wrist without marked instability
      of the whole DRUJ can be treated by arthroscopic suturing and satisfactory
      results can be expected. In case of clinical instability of the joint, it is to
      be assumed that the lesion extends to structures which cannot be seen and sutured
      arthroscopically. In these cases, open repair after arthroscopic examination must
      be considered.

PMID- 11518985
TI  - [Primary arthroscopic treatment of TFCC tears in fractures of the distal radius].
AB  - The primary simultaneous diagnosis and therapy of TFCC tears in distal radius
      fractures is still the exception. We present our results of arthroscopic
      treatment of these injuries. From January 1998 until September 1999, we treated
      21 patients with a type C fracture (AO classification) of the distal radius and
      one patient with a scaphoid fracture and TFCC tears. The Palmer 1A (n = 5) and 1
      C (n = 4) tears have been arthroscopically shaved as well as the meniscal tear (n
      = 1). The Palmer 1B tears were refixed either in an outside-inside technique (n =
      6) or in a new all-inside technique (n = 6). Palmer 1D tears were refixed in the
      Fellinger technique (n = 5). In the clinical follow-up examination six to fifteen
      months later, we saw symptoms of ulnar-sided wrist pain only in one case of a
      Palmer 1B tear treated in an outside-inside technique. Especially the patients
      treated by the new all-inside technique were free from symptoms of TFCC
      instability. We conclude, that arthroscopic treatment of TFCC tears in acute
      radius fractures is possible with good results. The new technique of all-inside
      repair is minimally invasive and shows good results.

PMID- 11518986
TI  - [Treatment of Galeazzi's fracture - is the surgical revision of the distal
      radioulnar joint necessary?].
AB  - PURPOSE: Fractures of the radial shaft associated with disruption of the distal
      radioulnar joint (DRUJ) are termed as Galeazzi-fractures. In Galeazzi's fracture,
      the aim of treatment is restoring the congruency of the joint and the stability
      of the DRUJ, thus preventing a loss of pronation or supination. PATIENTS AND
      METHOD: In this study, we included 24 patients (m = 22, f = 2) with 25 Galeazzi
      fractures treated between 1980 and 1998. Surgical treatment and the duration of
      therapy were analyzed retrospectively. The clinical and radiological results of
      15 patients were followed up. Two children were treated conservatively with
      immobilization in an above-the-elbow plaster. 19 patients were treated surgically
      by rigid internal fixation with a plate approximately one week after the
      accident. Four patients were treated initially in a different way. In 13 cases,
      the distal radioulnar joint was immobilized by pinning with Kirschner wires. In
      ten patients, the DRUJ showed no instability. Patients with DRUJ pinning received
      an above the elbow plaster for six weeks, the other patients received a forearm
      cast for the time of wound healing. RESULTS: Two patients developed a
      pseudarthrosis following Kirschner-wire or rush-pin osteosynthesis. The
      consolidation of remaining fractures was regular. In two patients, the DRUJ was
      not completely stable after temporary fixation. The remaining patients revealed a
      stable DRUJ. Eight patients showed a limited pro- or supination after temporary
      Kirschner wire fixation of the DRUJ. The other patients did not reveal a decrease
      in range of motion. CONCLUSION: A stable and optimal reduction and a rigid
      internal osteosynthesis are requisites for healing of the radius fracture. Open
      reduction of the DRUJ is only indicated when soft tissue interposition prevents
      exact reposition. Surgical revision of the distal radioulnar joint was not
      necessary in our patients. Patients after Kirschner-wire fixation showed a
      diminished pro- or supination. To prevent Kirschner-wire failure, postoperative
      cast immobilization is indicated. Due to the retrospective nature of the study it
      is not definitely clear if Kirschner wire fixation is superior to immobilization.

PMID- 11518987
TI  - [Viability monitor of free flaps in hypopharynx reconstruction].
AB  - Single-stage microvascular reconstruction of neck defects with jejunum or other
      free flaps are well established methods. However, these flaps usually are buried
      subcutaneously and viability surveillance is difficult. Alternatively to
      technical monitoring devices, we present a simple method using a "sentinel" part
      of the free jejunum flap transposed outside to the skin surface or sutured into
      the skin when using fasciocutaneous or myocutaneous flaps. Although this method
      is not new, it is rarely used. Compared to pure technical monitoring devices, it
      is easily performed and monitoring of buried free flaps especially in the neck
      region is reliable.

PMID- 11518988
TI  - [Plasma endotoxin, procalcitonin, C-reactive protein, and organ functions in
      patients with major burns].
AB  - Sepsis is one of the most frequent causes of death after major burn injury.
      Usually, sepsis appears as a consequence of a gram-negative bacteriaemia with
      release of endotoxins. In this study, the plasma endotoxin levels of seven
      patients (three female, four male; average age 51.3 +/- 23.8 years) with burns
      between 43.5 and 78 % Total Body Surface Area (Abbreviated Burn Severity Index 8 
      12) were determined for five days after thermal trauma every three hours by
      ELISA and compared with the concentration of procalcitonin (PCT) and C-reactive
      protein (CRP). A calculation of the Horrowitz-Index (PaO(2)/FiO(2)) and the
      Pressure-Adjusted Heart Rate (HR x CVP/MAP) took place to show a possible
      correlation between the endotoxin concentration and the cardiopulmonary organ
      function. Additionally, we analysed whether operative treatment can influence the
      level of plasma endotoxin in the early phase after burn injury. At any time after
      burn trauma, endotoxins could be detected in the plasma of all patients. Between
      the second and third day, there was a considerable increase in the endotoxin
      concentration with a maximum after 57 hours of 0.48 +/- 0.32 EU/ml. Two patients
      with sepsis and death in the further course had a rather distinctive increase.
      From the fourth day on, occasional episodes of increases in endotoxin
      concentration were noted. Postoperatively, there was a short increase in plasma
      endotoxin on the second and fourth day. The plasma endotoxin level showed no
      correlation with the PCT and CRP or with the oxygenation in the patients' blood.
      However, a positive correlation could be observed with the Pressure-Adjusted
      Heart Rate (p = 0.0061; r(2) = 0.212). An explanation for the endotoxin increase
      after 57 hours could be the translocation of intestinal bacteria, the beginning
      of bacterial colonisation or decomposition products of the burn wound with
      protein-protein complexes. Later on, infectious diseases such as pneumonia with
      gram-negative bacteria are of importance, too. According to the Two-Hit Model,
      the increase of plasma endotoxin can serve as a trigger and cause a recurrence of
      systemic inflammation with the changes observed in cardiac organ function,
      multiple organ dysfunction, and multiple organ failure.

PMID- 11518989
TI  - [The dynamic treatment of intraarticular fractures of the base of the middle
      phalanx with the Suzuki dynamic fixator].
AB  - Between 1994 and 1998, we have treated eleven patients with intraarticular
      fractures of the base of the middle phalanx including impaction, dislocation, and
      pilon types of injuries. All patients were evaluated after a median follow-up
      period of 25.8 (8 to 57) months. Treatment was carried out according to Suzuki's
      technique with a dynamic PIP-joint distraction fixator consisting of Kirschner
      wires and rubber bands. In five cases, there was additional osteosynthesis
      (Kirschner wires, resorbable hemicerclage) or cancellous bone-grafting for
      reconstruction of the joint surface. Early mobilisation commenced with active
      exercises for the PIP joint on the day of surgery. The dynamic extension fixator
      was applied for an average duration of 28 (15 to 42) days. By the time of follow
      up examinations, we found a range of motion on an average of 64 (0 to 105)
      degrees including a lack of extension of 11 (0 to 60) degrees and a median
      flexion capacity of 75 (30 to105) degrees. All fractures healed uneventfully with
      restored joint stability. Eight patients were completely painfree, three
      complained of mild occupational pain.

PMID- 11518990
TI  - [Operative treatment of vulnerable scars and deep soft-tissue defects of the
      thumb with a free toe pulp neurovascular flap].
AB  - Because of the capability of opposition, the thumb is the most important digit of
      the hand. In case of deep soft-tissue defects of the pulp, it is necessary to
      reconstruct the palmar surface of the distal phalanx of the thumb using tissue
      with good sensibility. Between 1982 and 1998 at the Department of Hand Surgery,
      Plastic and Microsurgery of the Berufsgenossenschaftliche Unfallkrankenhaus
      Hamburg, we used a free toe pulp neurovascular flap for reconstruction of the
      pulp of the thumb in nine patients. All flaps healed without complications.
      Indications, operative techniques, and results of this procedure are described.

PMID- 11518991
TI  - Skeletal reconstruction with a free vascularized fibula graft associated to bone
      allograft after resection of malignant bone tumor of limbs.
AB  - Over the last twenty years, progress in diagnosis and in adjuvant therapy in the
      field of malignant bone tumor treatment has allowed for development of limb
      saving surgical techniques after oncological excision. In this context, the use
      of vascularized fibula for transplantation represents an important instrument in
      the reconstruction of bone, either with or without allografts.Moreover, in
      pediatric cases, the vascularized transplant of the proximal fibula with its open
      physis allows for an adequate reconstruction of the bone loss and the possibility
      of conserving the growth potential of the segment. The purpose of this article is
      to illustrate the various reconstructive possibilities that the use of the
      combined graft technique (VFT plus allograft) offers in the treatment of large
      scale bone loss. In our department from 1988 to 2000, 142 vascularized fibula
      transplants were performed in oncological cases. Surgical reconstruction was
      carried out on the tibia in 70 cases, on the femur in 40, on the humerus in 26
      and on the radius in 6. Combined graft intercalary reconstructions were 92. In 22
      pediatric cases the fibula was transplanted, including the proximal growing
      epiphysis in the graft; in two of these cases massive allograft was associated to
      the VFG. Because of its biological properties, the grafted vascularized fibula
      allowed for fast bone fusion at the level of the osteotomy. It has also
      demonstrated a tendency of progressive hypertrophy and osteointegration with the
      allograft, when used. In 22 pediatric cases, the fibula graft with the proximal
      epiphysis maintained its ability to grow. Unsuccessful outcomes caused by
      vascular, mechanical, or septic failure were equal to 8.2 %. The fibula graft in
      the reconstruction of bone loss secondary to oncological excision is a
      trustworthy and versatile technique.

PMID- 11518992
TI  - [Stay away from surgery: ecthyma contagiosum].
AB  - 15 patients with Orf's disease were evaluated. Seven out of 15 patients (Group 1)
      were treated surgically because of different diagnoses. Seven patients who were
      misdiagnosed and treated surgically (Group 1), and eight patients (Group 2) were
      followed conservatively. The aim of this study is to compare the treatment period
      of the misdiagnosed surgically treated (Group 1) group and conservatively treated
      group (Group 2). Lesions were aggravated and delayed healing was observed in
      Group 1. Diagnosis of Orf disease may sometimes be difficult because of
      concominant bacterial superinfections and surgical trauma. Careful history and
      clinical findings point to the correct diagnosis. Contrary to other infections of
      the hand, surgery can cause further complications in this disease. Conservative
      treatment is the gold standard, even in complicated cases.

PMID- 11518993
TI  - [What's new in hepatobiliary surgery?].

PMID- 11518994
TI  - [Percutaneous laser ablation of malignant liver tumors].
AB  - PURPOSE: To present the technical data, methods and results of percutaneous laser
      ablation of malignant tumors. PATIENTS AND METHODS: In the period from June 1993
      to April 2000 a collective of 600 patients with malignant liver tumors and liver
      metastases from different primary tumors were treated via MR-guided LITT. After
      sonographically or CT-guided puncture MR-compatible laser catheters were
      positioned. The tumor destruction was visualized via MR-thermometry. The checkup
      and the therapy accomplishment ensued in the course of an ambulant therapy
      concept. RESULTS: In the course of a local accomplished LITT of liver metastases
      and malignant liver tumors a local tumor control rate of 97.8 % was achieved. The
      complication rate was extremely low with a value of 2.2 % (1 441 treatments). The
      lethality rate was 0.1 %. The mean survival time referring to the whole patient
      collective was 47.7 months, in the case of liver metastases from a colorectal
      cancer a value of 46.8 months was achieved. CONCLUSION: MR-guided LITT is a local
      effective therapy with low morbidity in malignant liver tumors with a maximum
      quantity of 5 and a size of </= 5 cm.

PMID- 11518995
TI  - [Radiofrequency ablation of liver tumours].
AB  - BACKGROUND: A variety of local treatment modalities exists for the palliative
      therapy of inoperable primary or secondary liver tumours. In this connection the
      promising use especially of thermal ablation methods has been reported recently.
      Numerous procedures and technical terms have been mentioned in this context
      giving us the opportunity of a review on this subject. METHODS: From the
      literature of the last five years (Medline/PubMed) including the lists of
      references physical principles and application techniques, indications and
      contraindications, possibilities of evaluation and results of high frequency
      thermotherapy (HFTT) respectively radiofrequency ablation (RFA) were investigated
      and compared to our own first experiences. Survival and recurrence rates were
      estimated from the study results. RESULTS: Most authors describe the HF
      thermoablative treatment as a technically uncomplicated and relatively low-risk
      procedure. After a mean follow-up of about 10 months the mean survival rate was
      about 90 % and tumor recurrence was seen in approximately 30 % of the patients.
      The main problems occurred in view of the complete registration of all tumors
      with imaging techniques before RFA and the complete ablation, especially of
      larger tumours. CONCLUSIONS: In most of the clinical studies RFA promises an
      advantage of survival and improvement of quality of life compared to the known
      courses of untreated liver tumours. Therefore this method should be practiced on
      a larger scale in suitable patients. At the same time its efficacy must be proven
      by comparative studies.

PMID- 11518996
TI  - [Surgical techniques in hepatic resections: Ultrasonic aspirator versus Jet
      Cutter. A prospective randomized clinical trial].
AB  - AIM OF THE STUDY: For all resection-techniques of liver tissue intra- and post
      operative blood-loss remains an important problem. Two novel resection-techniques
      the ultrasound-aspirator (CUSA) and the water-jet dissector (Jet-Cutter) appear
      to offer significant advantages regarding this problem. Aim of the present
      prospective clinical study was the comparison of these dissection techniques.
      MATERIAL AND METHODS: Prospective randomized study with the end points blood
      loss, length of surgery, tissue trauma and long-term survival. FINDINGS:
      Significant differences between both procedures with Jet-Cutter (n = 31) versus
      ultrasonic surgical aspirator CUSA (n = 30) were observed regarding length of
      resection and complete liver ischemia time (Pringle-time). Here significant
      advantages of the jet-cutter-technique were observed with 28 +/- 11 minutes
      length of resection versus 46 +/- 19 minutes and 29 +/- 12 minutes Pringle-time
      versus 39 +/- 16 minutes. Furthermore, significant fewer blood transfusions were
      required following jet-cutter-resection with a mean of 1.5 blood units vs. 2.5
      blood units using the CUSA. No differences were observed regarding postoperative
      long-term survival. CONCLUSIONS: The jet-cutter-technique is a fast and safe
      surgical procedure for liver resections and offers an attractive therapeutic
      alternative for various indications in liver surgery.

PMID- 11518997
TI  - [Danger of monopolar current in laparoscopic gallbladder surgery].
AB  - Monopolar electrosurgery is querried because of the availability of new
      preparation-techniques in laparoscopic cholecystectomy. The advantage of simple
      handling, cheap application and high efficiency has to be set against the danger
      of tissue lesions e. g. the damage of the bile duct as demonstrated by four own
      cases. Especially the bipolar preparation-method and ultrasonic dissection are
      safer, but expensive and not as fast and effective as monopolar technique. Laser
      heated instruments exist but are not in wide clinical use. The danger of tissue
      lesions can be reduced by accurate preparation-principles and caution in
      dissection of the Calot-triangle.

PMID- 11518998
TI  - [Therapy results of locoregional recurrences in rectal cancer].
AB  - Despite of advanced surgical technique and multimodality therapy results
      following secondary resection of local recurrence after rectal cancer are
      discussed controversially. PATIENTS AND METHODS: Between 1990 and 1999 81
      patients with local recurrence of rectal cancer were treated at our surgical
      department. Median age was 63 years, 62 % of patients were male. 98 % of
      recurrences were in local advanced stage (74 % = rT4, 25 % = rT3), 44 % of
      patients had synchronous distant metastases. RESULTS: 32 patients underwent
      resection of recurrent rectal cancer. Potential curative surgery was possible in
      56 % of resections. Extended resections of adjacent organs were necessary in 21
      patients. The 4-year survival in the curative group was 44 % compared to 19 % in
      patients with microscopic or gross residual disease. CONCLUSION: Optimistic long
      term results in recurrent rectal cancer can only be achieved after curative
      resection. Preoperative radiochemotherapy in advanced cancers increases curative
      resection and probably survival rate.

PMID- 11518999
TI  - [Anastomotic protection with a transanal tube after rectum resection and total
      mesorectal excision].
AB  - Between October 1998 and December 1999 50 patients with a primary cancer of the
      rectum were treated by sphincter saving anterior resection of the rectum and
      total mesorectal excision. Eight patients were given a neoadjuvant combined radio
      chemotherapy. The anastomoses were performed in the triple-stapling technique
      with a Premium Plus CEEA stapling device (Fa. Tyco Health Care, Tonisvorst,
      Germany) or with a Proximate ILS curved stapling device (Fa. Ethicon Endo
      Surgery, Norderstedt, Germany). The anastomoses were situated in 7 cm or in lower
      distance from the anal skin. In all patients with complete anastomotic tissue
      rings the anastomoses were protected with the transanal tube. The integrity of
      the anastomosis (n = 48) was checked for completeness in the 2nd and 12th
      postoperative week. The patients were sigmoidoscoped and the anastomoses were
      controlled by transanal ultrasonography. During the hospital stay 2 patients (4.2
      %) with a clinically evident anastomotic leakage were detected. 3 patients (6.2
      %) with an asymptomatic anastomotic leakage were detected by computertomography.
      The anastomoses of 27 patients (56.2 %) were clinically and by ultrasonographical
      examination intact. In these patients a postoperative radiogram was not
      indicated. Relaparotomy was necessary in one patient for bleeding, in two
      patients for anastomotic leaks and in three patients for ileus (12.5 %). Because
      of low anastomotic leakage rate and low morbidity we find the transanal tube to
      be at least equivalent to conventional colostoma for anastomotic protection.

PMID- 11519000
TI  - [Pathophysiology and clinical significance of the abdominal compartment
      syndrome].
AB  - Different causes, for example posttraumatic and postoperative complications, can
      lead to an elevated intra-abdominal pressure. Increased intraabdominal pressure
      effects cardiovascular, pulmonary and renal systems. The abdominal compartment
      syndrome can be defined as organ failure caused by an increased intra-abdominal
      pressure. Clinically the syndrome is characterised by a tensely distended
      abdomen, oliguria or anuria and/or inadequate ventilation. Early decompression by
      simple laparotomy and delayed closure is the treatment of choice. If untreated
      the abdominal compartment syndrome is lethal. Even treated it has a high
      morbidity and mortality as shown in our series where 2 out of 7 patients with
      this syndrome died despite surgical decompression.

PMID- 11519001
TI  - [Incidence of complications of the screw osteosynthesis of odontoid process
      fractures].
AB  - In this retrospective clinical study the incidence of complications in 58
      consecutive, with anterior screw fixation stabilized patients after fractures of
      the odontoid process is evaluated. In 51 patients the fracture has been defined
      as type II according to Anderson, in 6 patients an oblique type II fracture was
      present and one patient showed a cephalad type III fracture. Preoperatively, in
      only 19 % of the patients (n = 11) no dislocation of the dens occurred. 32
      patients were treated with single screw osteosynthesis, in 26 patients two screws
      were implanted. Significant complications with clinical relevance were registered
      in 14 patients (24 %), in 10 cases (17 %) an operative reintervention was
      required. Intraoperatively, in one patient a rupture of the carotid artery while
      winding around the motor drill occurred and in another case a complete
      malplacement of the screw posteriorly to the odontoid process was observed. A
      clearly excentric positioning of the implant was evaluated in 5 patients with a
      consecutive high rate of implant migration (n = 3). Two patients died
      perioperatively not related to the cervical injury. Postoperatively, one patient
      with a wound infection due to an iatrogenic perforation of the esophagus required
      reoperation as well as 4 patients with instability because of implant migration.
      Patients beyond the age of 65 years (n = 3) were significantly overrepresented in
      that group. In one case, the secondary intervention was caused by a
      pseudarthrosis of the dens axis. Complications without any relevance to the
      clinical and functional long term result were fusions in malposition of the
      odontoid process in 14 patients (24 %) and 10 (17 %) marginal screw perforations
      laterally. Differences in the use of one or two screws have not been observed in
      this study, although the investigations showed a tendency between marginal
      lateral screw perforations and double screw osteosynthesis and an increasing
      number of complications in the geriatric cohort.

PMID- 11519002
TI  - [Mechanical stimulation of venous blood flow in below-the-knee plaster cast].
AB  - Physical methods became recently more important as an alternative to
      anticoagulation for prophylaxis of thromboembolism and were studied for their
      efficacy. The AV-impulse-system proved efficient in reducing thromboembolic
      complications in patients undergoing hip surgery by increasing the return of
      venous blood in the deep veins of the leg. In a preclinical trial we studied the
      influence of the AV-impulse-system and of active forefoot movement on venous
      blood return in 12 lower extremities of 6 healthy individuals immobilized in
      below the knee plaster casts. Our results show a significant increase in venous
      blood flow caused by the AV-impulse-system (p < 0.05) and by active forefoot
      movements (p < 0.05). Prevention of thromboembolic complications in trauma and
      orthopaedic patients immobilized in plaster cast seems possible by using the AV
      impulse-system which significantly increases the venous blood flow independent
      from patient compliance.

PMID- 11519003
TI  - [Conceptual and practical aspects of creating an internet presentation of a
      surgical department].
AB  - Until recently an internet presentation of a surgical department could rarely be
      found on the World Wide Web (WWW). Today an increasing number of departments
      provide a Web site, but often contents and graphics can still be improved. For
      more than 4 years the Department of Surgery at the University Hospital of
      Wurzburg has maintained an internet presentation (www.chirurgie.uni
      wuerzburg.de). Contents and technical features have been continuously updated. In
      order to provide a powerful Web site, contents were structured for the 3 target
      groups: visitors, that are patients including their relatives (consultation
      hours, directions, maps of campus and wards), physicians (main points in
      diagnostics and therapy, research, publications, further education, job offers)
      and medical students (teaching schedules, courses, learning materials).
      Concerning the technical aspects of the Web site, emphasis was put on a distinct
      layout and clear design. Therefore, text was arranged in tables or lists and a
      limited number of standard fonts was used. Graphics were compressed to a minimum
      file size. To allow effortless navigation for the visitor two roll-over menu
      banners, a sitemap, a search tool and easy-to-follow symbols were implemented.
      The internet is an important source of information, and used correctly, the WWW
      is very useful for the presentation and communication of a surgical department.

PMID- 11519004
TI  - [The giant, pendulant goiter. A case report].
AB  - A 48-year-old woman with a monstrous goiter was referred to our hospital. She
      noticed a growth of the goiter for about 20 years, until now she did not undergo
      surgery because she was afraid of the operation. In September 1999 she suffered
      from a cardiac decompensation because of a hyperthyreosis, so she decided to be
      operated. The examination showed a giant goiter, placed in front of the sternum.
      After a detailed check of risk factors, we resected the goiter in general
      anaesthesia. The thyroid gland weighed 5 100 grams, in the histologic examination
      no signs of malignancy were found. Postoperatively, a hypocalcaemia occurred,
      without clinical symptoms. The patient was discharged on the 6th postoperative
      day.

PMID- 11519005
TI  - [Spontaneous splenic rupture in metastatic malignant melanoma].
AB  - Spontaneous splenic rupture is a rare cause of non-traumatic haemorrhage and is
      of infectious origin in most instances. We present a patient under treatment for
      abdominal manifestations of metastatic malignant melanoma who developed signs of
      haemorrhagic shock and where, upon emergency laparotomy, metastases were found to
      have caused rupture of the spleen. The patient recovered after splenectomy and
      was continued on systemic chemoimmunotherapy. One year after the incident he died
      of cerebral metastases.

PMID- 11519007
TI  - [Analysis of inline-skating and mountainbiking injuries in a tourism area].

PMID- 11519006
TI  - [Acute retrocecal appendicitis caused by an Actinomyces israelii mixed
      infection].
AB  - We report the rare case of a retrocecal appendicitis in an adult caused by an
      Actinomyces israelii mixed infection. Suspecting an acute appendicitis the
      explorative laparotomy was performed. Appendectomy with extensive drainage of the
      abscess and subsequent high-dose penicillin therapy over several months were the
      definitive treatment, resulting in complete healing. Special features of clinical
      symptomatology and problems concerning diagnosis and differential diagnosis are
      discussed.

PMID- 11519008
TI  - [Notes on the surgical history of Strasbourg (Part 2)].

PMID- 11519009
TI  - Reevaluation of antibiotic breakpoints.
AB  - Differences in antibiotic breakpoints have resulted from differences in clinical
      practice and in interpretation of the parameters that are considered when
      breakpoints are set. Differences in the first of these are less common for newer
      agents, whereas differences in the latter could be resolved by consensus
      discussions. Greater difficulty arises when common pathogens acquire resistance,
      especially when this occurs by degrees, as has happened with penicillin for
      gonococci and the pneumococci, and for the fluoroquinolones in relation to a wide
      variety of bacterial species. Changes to breakpoints under such circumstances
      should be introduced only after the most careful consideration and the education
      of diagnostic microbiologists and clinicians.

PMID- 11519010
TI  - Evidence of linkage with HLA-DR in DRB1*15-negative families with multiple
      sclerosis.
AB  - The importance of the HLA-DR locus to multiple sclerosis (MS) susceptibility was
      assessed in 542 sib pairs with MS and in their families. By genotyping 1,978
      individuals for HLA-DRB1 alleles, we confirmed the well-established association
      of MS with HLA-DRB1*15 (HLA-DRB1*1501 and HLA-DRB5*0101), by the
      transmission/disequilibrium test (chi2=138.3; P<.0001). We obtained significant
      evidence of linkage throughout the whole data set (mlod=4.09; 59.9% sharing).
      Surprisingly, similar sharing was also observed in 58 families in which both
      parents lacked the DRB1*15 allele (mlod=1.56; 62.7% sharing; P=.0081). Our
      findings suggest that the notion that HLA-DRB1*15 is the sole major
      histocompatibility-complex determinant of susceptibility in northern-European
      populations with MS may be incorrect. It remains possible that the association of
      MS with HLA-DRB1*15 is due to linkage disequilibrium with a nearby locus and/or
      to the presence of disease-influencing allele(s) in DRB1*15-negative haplotypes.

PMID- 11519012
TI  - Are there really too many biomedical trainees?

PMID- 11519011
TI  - Mutations in the 3beta-hydroxysterol Delta24-reductase gene cause
      desmosterolosis, an autosomal recessive disorder of cholesterol biosynthesis.
AB  - Desmosterolosis is a rare autosomal recessive disorder characterized by multiple
      congenital anomalies. Patients with desmosterolosis have elevated levels of the
      cholesterol precursor desmosterol, in plasma, tissue, and cultured cells; this
      abnormality suggests a deficiency of the enzyme 3beta-hydroxysterol Delta24
      reductase (DHCR24), which, in cholesterol biosynthesis, catalyzes the reduction
      of the Delta24 double bond of sterol intermediates. We identified the human
      DHCR24 cDNA, by the similarity between the encoded protein and a recently
      characterized plant enzyme--DWF1/DIM, from Arabidopsis thaliana--catalyzing a
      different but partially similar reaction in steroid/sterol biosynthesis in
      plants. Heterologous expression, in the yeast Saccharomyces cerevisiae, of the
      DHCR24 cDNA, followed by enzyme-activity measurements, confirmed that it encodes
      DHCR24. The encoded DHCR24 protein has a calculated molecular weight of 60.1 kD,
      contains a potential N-terminal secretory-signal sequence as well as at least one
      putative transmembrane helix, and is a member of a recently defined family of
      flavin adenine dinucleotide (FAD)-dependent oxidoreductases. Conversion of
      desmosterol to cholesterol by DHCR24 in vitro is strictly dependent on reduced
      nicotinamide adenine dinucleotide phosphate and is increased twofold by the
      addition of FAD to the assay. The corresponding gene, DHCR24, was identified by
      database searching, spans approximately 46.4 kb, is localized to chromosome
      1p31.1-p33, and comprises nine exons and eight introns. Sequence analysis of
      DHCR24 in two patients with desmosterolosis revealed four different missense
      mutations, which were shown, by functional expression, in yeast, of the patient
      alleles, to be disease causing. Our data demonstrate that desmosterolosis is a
      cholesterol-biosynthesis disorder caused by mutations in DHCR24.

PMID- 11519013
TI  - Neuron addition and neurogenesis are not interchangeable terms.

PMID- 11519015
TI  - Predicting results of morphology teaching in non-English-speaking countries.

PMID- 11519016
TI  - The 2001 Henry Gray award.

PMID- 11519017
TI  - Communicating science: from the laboratory bench to the breakfast table.
AB  - If we are to maintain public appreciation and support for our scientific
      enterprise, we need to pay more attention to translating the benefits and
      grandeur of science into the language of broader society. Both educators and
      journalists have a role to play in communicating the achievements of science, but
      scientists must recognize that we have a responsibility to increase the
      availability and salience of science to the public.

PMID- 11519018
TI  - Iulius Casserius (1552-1616): the self-made anatomist of Padua's golden age.

PMID- 11519019
TI  - Reappraisal of the vomeronasal system of catarrhine primates: ontogeny,
      morphology, functionality, and persisting questions.
AB  - The vomeronasal organ (VNO) is a chemosensory organ that functions in sociosexual
      communication in many vertebrates. In strepsirhine primates and New World
      monkeys, the bilateral VNOs are traditionally understood to exist as a well
      developed chemosensory epithelial unit. In contrast, the VNOs of catarrhine
      primates are thought to be absent or exist only as reduced epithelial tubes of
      uncertain function. However, the VNO of New World monkeys shows substantial
      variation in the extent of sensory epithelium. Recent findings that the
      chimpanzee (Pan troglodytes) possesses a VNO similar to humans suggest the
      variability of the VNO among haplorhine primates may be more extensive than
      previously thought, and perhaps more at par with that observed in chiropterans.
      The atypical histologic structure and location of the human/chimpanzee VNO
      suggest accessory glandular secretion and transport functions. Other catarrhine
      primates (e.g., Macaca spp.), may truly be characterized by VNO absence. Unique
      aspects of facial growth and development in catarrhine primates may influence the
      position or even presence of the VNO in adults. These recent findings demonstrate
      that previous investigations on some catarrhine primates may have missed the VNO
      and underestimated the extent of variability. As an understanding of this
      variation increases, our view of VNO functionality and associated terminology is
      changing. Further investigations are needed to consider phylogenetic implications
      of VNO variability and the association of craniofacial form and VNO anatomic
      position in primates.

PMID- 11519020
TI  - Virtual anthropology (VA): a call for glasnost in paleoanthropology.
AB  - The adventurous scientist, with a hat protecting him from the fierce sun as he
      travels from one remote place to another, hunting for fossils of our ancestors,
      has been a part of the romantic imagination associated with anthropological
      research in the 20th Century. This picture of the paleoanthropologist still
      retains a grain of truth. Indeed, many new sites were discovered under
      troublesome conditions in the recent past and have added substantial information
      about our origins. But on another front, probably less sensational but no less
      important, are contributions stemming from the analysis of the already discovered
      fossils. With the latter, a rapid evolution in anthropologic research took place
      concurrently with advances in computer technology. After ambitious activities by
      a handful of researchers in some specialized laboratories, a methodologic
      inventory evolved to extract critical information about fossilized specimens,
      most of it preserved in the largely inaccessible interior as unrevealed anatomic
      structures. Many methodologies have become established but, for various reasons,
      access to both the actual and the digitized fossils is still limited. It is time
      for more transparency, for a glasnost in paleoanthropology. Herein are presented
      some answers to the question of how a high-tech approach to anthropology can be
      integrated into a predominantly conservative field of research, and what are the
      main challenges for development in the future.

PMID- 11519022
TI  - A history of cancer rehabilitation.
AB  - More than 8 million people in the United States have a history of cancer and more
      than 1 million new cancers are diagnosed each year. The 5-year survival rates for
      most tumors continue to improve due to earlier detection and treatment
      strategies. With increased cancer survival rates, there is a greater need for
      physiatrists (physicians trained in physical medicine and rehabilitation) to
      coordinate rehabilitation services and prepare a comprehensive plan for treatment
      and follow-up. Rehabilitation for patients with cancer should be no different
      from rehabilitation for other diagnostic conditions. The ultimate goal should be
      the achievement of the highest functional status possible within the limits of
      the disease and the patient's choices. Physiatrists have training that enables
      them to assess functional disability, biomechanics, quality of life, and human
      development, as well as the knowledge to prescribe appropriate medications,
      modalities, and orthotic, prosthetic, and assistive devices. An examination of
      the history of cancer rehabilitation will steer us toward future success for our
      patients. It is important that past lessons direct us away from pitfalls, and
      that patients receive the rehabilitation services to which they are entitled.

PMID- 11519023
TI  - Cancer rehabilitation into the future.
AB  - The 5-year survival for many cancer sites exceeds 50%, suggesting that these
      patients are living longer and may be considered to have a chronic illness. The
      incidence of cancer increases from 500 in 100,000 to 2000-4000 in 100,000 as
      women or men age from 50 to 80 years. Our population is aging and the prevalence
      of cancer is increasing. Treatments for cancer are quite complex, and they are
      often delivered to elders who have a variety of medical problems and are
      receiving additional medications that may complicate overall patient management.
      Hence, these patients may have extremely complex functional problems. Cancer
      patients need comprehensive care designed to relieve symptoms of pain, fatigue,
      and weakness. They need education to help support their ability to reach
      functional independence and maintain quality of life. Rehabilitation
      professionals are essential for the comprehensive care of cancer patients
      throughout the phases of their disease: treatment planning, treatment, remission,
      recurrence, and end of life. The needs of this population can better be served if
      several processes are put into effect. Rehabilitation professionals must be
      trained to manage problems associated with cancer and its treatments. Research
      about what are effective and efficient rehabilitation treatments must be done to
      determine how best to treat cancer patients throughout the various phases of
      their illness. Physicians and patients must be alerted to the importance of
      rehabilitation interventions to the overall function of these patients.

PMID- 11519024
TI  - Lymphedema: strategies for management.
AB  - An important sequela of cancer treatment is lymphedema. Management of this
      condition must be based on the physiologic functioning of the lymphatic system
      and tailored to the individual patient's presentation of the disease. Early
      diagnosis and treatment are essential to prevent worsening of the condition and
      to help assuage the psychologic impact of the disease. A review of the normal and
      impaired lymphatic system is presented in this article. Current assessment and
      treatment options are described, including education of patients in precautions,
      positioning, exercise, compression garments and bandages, pneumatic pumps, and
      lymphatic massage. Also included is a discussion of the psychologic impact of the
      disease as well as management of psychologic symptoms. Various strategies for
      management of the physical aspects of lymphedema are available. Studies have
      shown that use of physical treatments such as exercise, compression, and
      lymphatic massage are effective in reducing the amount of swelling in affected
      limbs. The specific type, amount, and combination of these treatments continues
      to be debated. The development of lymphedema is commonly associated with
      significant psychologic distress that can impact on compliance with physical
      treatments. Because there is no consensus as to the optimal treatment approach
      for management of lymphedema, additional research must ensue to determine the
      efficacy of existing treatments and to develop new management techniques.
      Clinicians must be attuned to the signs and symptoms of lymphedema in order to
      make prompt referrals for treatment.

PMID- 11519025
TI  - Strategies for managing cancer-related fatigue syndrome: a rehabilitation
      approach.
AB  - Although technologic advances and insights into the mechanisms of cancer and
      cancer treatments have resulted in hope of increased survival and even cure in
      many cancer populations, parallel efforts to promote quality of life through a
      commitment to rehabilitation and aggressive palliation have lagged. Recent
      studies have demonstrated fatigue to be the most distressing phenomenon
      experienced by cancer patients. This article examines fatigue from a
      rehabilitation perspective. Application of innovations in therapeutic exercise
      training, diet therapy, sleep therapy, cognitive therapy, and pharmacologic
      therapy and their attendant rationales are discussed. From clinical as well as
      research perspectives of palliation and rehabilitation, the manifestations of
      fatigue are better appreciated if fatigue is conceptualized as a syndrome,
      namely, cancer-related fatigue syndrome (CRFS). Experience of CRFS by cancer
      patients, regardless of their diagnosis, stage of disease, treatment regimen, or
      age, influences all aspects of quality of life and aggravates the experience of
      other distressing symptoms such as pain, nausea, and dyspnea. Understanding the
      underlying mechanisms for energy loss and gain, as well as the relationship
      between the right amount and type of activity and sleep, can lead toward more
      effective and innovative rehabilitation programs. Development of research based
      clinical interventions in these areas holds promise for significant improvement
      in functioning and quality of life for cancer survivors and may constitute
      valuable rehabilitative techniques that can be adjunctive to standard therapies.

PMID- 11519026
TI  - Rehabilitation following bone marrow transplantation.
AB  - Bone marrow transplantation and stem cell transplantation are increasingly used
      to treat hematologic malignancies and some solid tumors. The treatment entails
      bone marrow-ablative therapies and intensive medical support to sustain the
      patient through pancytopenia and other complications of the disease,
      transplantation process, or drug side effects. Patients who develop graft-versus
      host disease are the most difficult subset of transplant recipients to manage.
      Most transplant recipients perform at normal or near-normal functional levels at
      the inception of the transplantation process but are at high risk for developing
      functional deficits as a result of cumulative impairments. These impairments
      arise from their disease, their prior cancer treatment, transplant induction,
      graft-versus-host disease, immobility, infection, steroid-related side effects,
      and other sequelae of transplantation. Preventive and preemptive rehabilitation
      interventions can minimize functional loss and facilitate recovery, but the
      transplantation team must be sensitive to and regularly assess for early
      functional declines in these patients. The physiatrist and the other members of
      the rehabilitation team must be thoroughly acquainted with the unique needs and
      challenges of the bone marrow transplantation population in order to design and
      modify treatment programs effectively and safely. Outcome research has shown that
      some patients have continued limitations in function despite successful
      transplantation. Few evidence-based data are available that addresses factors
      correlating with poor functional outcomes other than graft-versus-host disease.
      However, this disease has not been investigated utilizing objective functional
      instruments. Future research should more clearly elucidate the functional impact
      of allogeneic and autologous transplants by using standardized physical
      performance measures as well as thorough function-based symptomatology
      questionnaires.

PMID- 11519027
TI  - Sexuality rehabilitation.
AB  - Sexual dysfunction is a common problem for patients with cancer as well as cancer
      survivors. Unfortunately, sexual difficulties are often not identified by the
      cancer care team, and most patients receive little or no assistance in dealing
      with the effects of cancer and its treatment on intimacy. In this article,
      recommendations concerning assessment of sexual function are presented and
      various treatments are reviewed. The authors recommend that questions concerning
      sexual difficulties and intimacy be incorporated into the initial evaluation of
      patients with cancer. The assessment of sexual difficulties should continue
      throughout treatment and recovery. The cancer care team can initiate
      interventions including patient education and treatments for altered desire,
      erectile dysfunction, and estrogen deficiency. These interventions may result in
      marked improvement in symptoms. Some forms of sexual dysfunction may require
      referral to a specialist. Based on their experience, the authors conclude that
      assessment and treatment of sexual dysfunction in patients with cancer should
      become standard practice, and that quality of life is enhanced when attention to
      the sexual consequences of cancer and its treatment are addressed.

PMID- 11519028
TI  - Rehabilitation for limb salvage patients: kinesiological parameters and
      psychological assessment.
AB  - Osteosarcoma is the most frequently occurring primary malignant tumor of bone,
      especially in adolescence. Treatment involves either limb salvage surgery or
      amputation with neoadjuvant chemotherapy. This review article discusses the
      current treatment modalities for osteosarcoma and also compares the gait patterns
      and psychosocial profiles of patients treated with either limb salvage surgery or
      amputation for osteosarcoma. Contemporary orthopedic literature on therapeutic
      options for osteosarcoma patients is reviewed. Background information on the
      basic principles of kinesiology, with emphasis on studies of gait pattern
      differences among patients treated with limb salvage versus amputation, is
      presented. Finally, several studies of the psychologic profiles of patients after
      these two procedures for osteosarcoma are reviewed. Trends in contemporary
      orthopedic literature suggest that functional outcomes, in terms of kinesiologic
      parameters, are comparable for patients treated with either limb salvage or
      amputation. Both sets of patients reported quality-of-life problems, including
      difficulty retaining health insurance and finding appropriate employment, social
      isolation, and poor self-esteem. The management of patients with osteosarcoma
      includes not only an individualized surgical plan for each patient but also
      includes awareness of the patients' psychologic and social needs after surgery.

PMID- 11519029
TI  - Bone metastasis and rehabilitation.
AB  - Patients with cancer that has metastasized to bone will frequently develop
      functional problems that may respond to rehabilitative treatment. Many
      rehabilitation professionals, however, are concerned about the possibility of
      producing pathologic fracture with their treatment. Several methods have been
      proposed for identifying which malignant lesions in bone are at risk of fracture.
      In this article, these methods are reviewed and statistical analyses of them are
      presented. The risk of rehabilitating patients with bony metastases is also
      reviewed, as are the reported outcomes of these rehabilitation efforts. Standard
      approaches to the rehabilitation of these patients have evolved, although most of
      them have not been rigorously validated, and these are discussed. None of the
      methods for identifying lesions at risk of pathologic fracture are useful in
      other than long bones, and they are limited even there. The risk of producing
      pathologic fractures in cancer patients by increasing mobility and function,
      however, is low. Satisfactory outcomes have been demonstrated in attempting to
      rehabilitate patients who have had recent surgical repair of pathologic or
      impending fractures. Rehabilitation of cancer patients with bony metastases can
      be safely and effectively accomplished using standard approaches to the treatment
      of these patients.

PMID- 11519030
TI  - Rehabilitation of persons with central nervous system tumors.
AB  - A tumor that affects the central nervous system can have a dramatic impact on the
      individual affected, as well as his or her family and friends. The tumor,
      regardless of extent or location, may affect the physical, social, vocational,
      and emotional capabilities of the individual. Basic aspects of rehabilitation for
      patients with tumors affecting the brain and spinal cord are reviewed in this
      article. The authors have found that the same principles of neurorehabilitation
      applied to persons with traumatic brain injury, stroke, and traumatic spinal cord
      injury are equally appropriate for persons with brain and spinal cord tumors.
      These principles include the prevention of medical complications; the treatment
      of medical problems such as pain, spasticity, and neuropathic bowel and bladder;
      and the improvement of patients' mobility and activities of daily living.
      Rehabilitation specialists can help prevent complications, maximize function, and
      improve the quality of life for patients with central nervous system tumors.

PMID- 11519031
TI  - Rehabilitation of patients with advanced cancer.
AB  - Despite growing interest in advanced cancer patients' quality of life, little
      attention has been directed toward preservation or recovery of their function.
      Although there is a dearth of supportive literature, extensive experience with
      other advanced disease populations suggests that standard, widely available
      rehabilitation strategies can enhance function in cancer. Logistic challenges to
      the provision of adequate rehabilitation to advanced cancer patients is discussed
      in this article, based on the author's experience and discussions in the
      literature. Common sources of functional impairment are reviewed with elucidation
      of rehabilitation approaches likely to benefit affected patients. Appropriate
      physical and occupational therapy techniques, as well as appropriate orthotics,
      assistive devices, and environmental modifications, are outlined for each of
      these impairments. In the author's view, rehabilitation should be considered for
      all advanced cancer patients experiencing functional decline. Pathways and
      referral patterns need to be established so that timely and appropriate
      functional restoration may occur.

PMID- 11519032
TI  - Palliative care and rehabilitation.
AB  - Disability in patients with advanced cancer often results from bed rest,
      deconditioning, and neurologic and musculoskeletal complications of cancer or
      cancer treatment. Terminally ill patients have a high prevalence of weakness,
      pain, fatigue, and dyspnea in addition to other symptoms. Rehabilitation and
      palliative care have emerged as two important parts of comprehensive medical care
      for patients with advanced disease; this article discusses the relationship
      between the two and the possible role of rehabilitation interventions in the care
      of terminally ill patients. Palliative care and rehabilitation share common goals
      and therapeutic approaches. Both disciplines have a multidisciplinary model of
      care, which aims to improve patients' levels of function and comfort. There is
      scarce evidence that rehabilitation interventions can impact function and symptom
      management in terminally ill patients. However, clinical experience suggests that
      the application of the fundamental principles of rehabilitation medicine is
      likely to improve their care. Physical function and independence should be
      maintained as long as possible to improve patients' quality of life and reduce
      the burden of care for the caregivers. Future research on the rehabilitation of
      terminally ill patients should focus on better understanding the role of
      rehabilitation and defining appropriate interventions. The development of an
      evidence-based body of knowledge will ensure that these patients receive
      appropriate rehabilitation interventions.

PMID- 11519033
TI  - Cancer rehabilitation services in a tertiary care center.
AB  - People with cancer often have functional limitations resulting from fatigue,
      deconditioning, pain, or metastasis to the musculoskeletal or nervous system, in
      addition to the psychosocial aspects of dealing with their disease. Their medical
      caregivers often focus on treating the disease and overlook these important
      aspects. The Department of Physical Medicine and Rehabilitation at the Mayo
      Clinic developed a Cancer Rehabilitation Service in 1979 to address these needs
      for hospitalized patients. Some of the challenges and successes of this service
      are briefly discussed in this article.

PMID- 11519034
TI  - Integrating cancer rehabilitation into medical care at a cancer hospital.
AB  - In spite of national health care legislative and model program initiatives,
      cancer rehabilitation has not kept pace with rehabilitation for patients with
      other medical problems. This article discusses, from a historical perspective,
      unsuccessful health care legislation related to cancer and problems in
      establishing and expanding cancer rehabilitation programs. The attempts to
      establish a cancer rehabilitation program at the Texas Medical Center and the
      University of Texas M. D. Anderson Cancer Center are reviewed. Lessons learned
      over past 40 years and strategies for maintaining the success of a cancer
      rehabilitation program are discussed.

PMID- 11519035
TI  - No EWS/FLI1 fusion transcripts in giant-cell tumors of bone.
AB  - Giant-cell tumor of bone (GCT) is a locally aggressive neoplasm of unknown
      etiology and pathogenesis. Cytogenetically, no consistent chromosomal
      alterations, apart from telomeric associations involving various chromosome ends,
      have been described. Recently, however, it was reported that by using highly
      sensitive nested RT-PCR, a high proportion of GCT displays chimeric EWS/FLI1
      fusion transcripts, i.e., the molecular genetic feature previously known to be
      strongly associated with the Ewing family of tumors. Thus, we decided to perform
      single-step and nested RT-PCR analyses on fresh frozen samples from 10 cases of
      GCT, all of which had also been subjected to cytogenetic analysis. After short
      term culturing, none of the samples displayed any t(11;22)(q24;q12), the
      translocation characteristically giving rise to the EWS/FLI1 fusion, nor any
      other type of rearrangement of 11q24 or 22q12. Furthermore, in none of the cases
      did the RT-PCR analysis, whether single step or nested, result in products
      corresponding to a hybrid EWS/FLI1 transcript. On the basis of these results, we
      conclude that translocations leading to fusion of the EWS and FLI1 genes are not
      part of the pathogenesis of GCT.

PMID- 11519036
TI  - Gelsolin functions as a metastasis suppressor in B16-BL6 mouse melanoma cells and
      requirement of the carboxyl-terminus for its effect.
AB  - Gelsolin, an actin-binding protein, is implicated as a critical regulator in cell
      motility. In addition, we have reported that cellular levels of gelsolin are
      decreased in various tumor cells, and overexpression of gelsolin by gene transfer
      suppresses tumorigenicity. We sought to assess the effects of gelsolin
      overexpression on metastasis and to determine the importance of a carboxyl
      terminus that confers Ca(2+) dependency on gelsolin for effects of its
      overexpression. Expression vectors with cDNA encoding either full-length wild
      type or His321 mutant form, isolated from a flat revertant of Ras-transformed
      cells and a carboxyl-terminal truncate, C-del of gelsolin, were transfected into
      a highly metastatic murine melanoma cell line, B16-BL6. Expression of introduced
      cDNA in transfectants was confirmed using Western blotting, 2-dimensional gel
      electrophoresis and reverse transcription-polymerase chain reaction (RT-PCR). We
      characterized phenotypes of transfectants, such as growth rate, colony formation
      in soft agar, cell motility and metastasis formation in vivo. Transfectants
      expressing the wild-type, His321 mutant and C-del gelsolin exhibited reduced
      growth ability in soft agar. Although expression of integrin beta1 or alpha4 on
      the cell surface of transfectants was not changed, wild-type and His321 mutant
      gelsolin, except for C-del gelsolin, exhibited retardation of cell spreading,
      reduced chemotatic migration to fibronectin and suppressed lung colonization in
      spontaneous metastasis assay. Gelsolin may function as a metastasis suppressor as
      well as a tumor suppressor gene. The carboxyl-terminus of gelsolin is important
      for retardation of cell spreading, reduced chemotasis and metastasis suppression.

PMID- 11519037
TI  - Paracrine angiogenic loop between head-and-neck squamous-cell carcinomas and
      macrophages.
AB  - Angiogenesis, an essential step in the development of neoplasia, is a complex
      process that involves the interaction of tumor cells with stromal cells. Tumor
      associated macrophages (TAMs) can participate in the induction of tumor
      angiogenesis and are thought to be of prognostic value in some neoplasms. We have
      investigated how macrophages contribute to angiogenesis in head-and-neck squamous
      cell carcinoma (HNSCC) and have found that tumor cells attract monocytes and
      activate them to secrete angiogenic factors. The attraction of macrophages was
      due to the secretion of monocyte chemotactic protein-1 and TGF-beta1 by tumor
      cells, while tumor production of TGF-beta1 was responsible for activating
      macrophages. In addition, activated macrophages produced cytokines that acted in
      a paracrine fashion by secreting both TNF-alpha and IL-1, which in turn
      stimulated tumor cells to secrete increased levels of IL-8 and VEGF. These data
      demonstrate that TAMs play an important role in the in vivo induction of
      angiogenesis in HNSCC and suggest that anti-angiogenic therapies for HNSCC and
      perhaps other neoplasms must include strategies that will block the ability of
      tumor cells to recruit macrophages into the tumor micro-environment.

PMID- 11519038
TI  - Expression of E1AF/PEA3, an Ets-related transcription factor in human non-small
      cell lung cancers: its relevance in cell motility and invasion.
AB  - Cell invasion and metastasis characterize the malignant potential of non-small
      cell lung cancers (NSCLCs). We have previously reported that E1AF, a member of
      the Ets-related transcription factor family, confers invasive phenotype on breast
      cancer and oral squamous-cell carcinoma cell lines. In our study, we analyzed the
      E1AF expression in cell lines and resected tumors of NSCLCs by Northern blot and
      in situ hybridization analyses and found that 15 of 17 cell lines and 12 of 19
      tumors expressed E1AF mRNA while normal lung tissue and concomitant normal cells
      within tumors did not. To examine the biologic importance of E1AF in NSCLCs, we
      introduced the E1AF gene into VMRC-LCD and NCI-H226, NSCLC cell lines lacking
      E1AF expression, and examined cell motility and invasion activities. E1AF
      transfected VMRC-LCD cells showed increased cell motility that was 2-fold that of
      parental and vector-transfected control cells (p < 0.01), and both cell motility
      and invasion were increased 1.6-fold in NCI-H226 (p < 0.01). Furthermore,
      hepatocyte growth factor (HGF), which is one of the most effective cell
      scattering factors, stimulated the motile and invasive activities in E1AF
      transfected VMRC-LCD and NCI-H226 cells but not in their parental or vector
      transfected control cells. Ets-1 mRNA expression was found in E1AF-transfected
      VMRC-LCD cells but not in parental or vector-transfected cells. HGF further
      induced expression of the Ets-1 and urokinase-type plasminogen activator (uPA)
      genes specifically in E1AF-transfected cells. These findings suggest that E1AF
      plays a substantial role in the cell motility and invasion of NSCLCs.

PMID- 11519039
TI  - Induction of urokinase-type plasminogen activator by the anthracycline antibiotic
      in human RC-K8 lymphoma and H69 lung-carcinoma cells.
AB  - Current evidence has suggested the possible involvement of ROS as signaling
      messengers in IL-1beta- or LPS-induced gene expression. We previously reported
      that both IL-1beta and LPS induce uPA in RC-K8 human lymphoma cells. Here, we
      provide evidence that ROS-generating anthracycline antibiotics, including
      doxorubicin and aclarubicin, upregulate uPA expression in 2 human malignant cell
      lines, RC-K8 and H69 small-cell lung-carcinoma cells. Both doxorubicin and
      aclarubicin markedly increased uPA accumulation in RC-K8- and H69-conditioned
      medium in a dose-dependent manner. In each case, maximal induction was observed
      at a sublethal concentration, i.e., at a concentration where cell growth was
      slightly inhibited. Both doxorubicin and aclarubicin increased uPA mRNA levels,
      and induction in each case reached the maximal level 9 hr after stimulation.
      Doxorubicin barely changed the half-life of uPA mRNA and activated uPA gene
      transcription. Antioxidants such as NAC and PDTC inhibited doxorubicin-induced
      uPA mRNA accumulation. Microarray analysis, using Human Cancer CHIP version 2
      (Takara Shuzo, Kyoto, Japan), in which 425 human cancer-related genes were
      spotted on glass plates, revealed that uPA is 1 of 3 genes that were clearly
      upregulated in H69 cells by doxorubicin stimulation. These findings suggest that
      the anthracycline induces uPA in human malignant cells by activating gene
      transcription in which ROS may be involved. Therefore, by upregulating uPA
      expression, the anthracycline may influence many biologic cell functions mediated
      by the uPA/plasmin system.

PMID- 11519040
TI  - Reduced expression of the Aalpha subunit of protein phosphatase 2A in human
      gliomas in the absence of mutations in the Aalpha and Abeta subunit genes.
AB  - Protein phosphatase 2A (PP2A) consists of 3 subunits: the catalytic subunit, C,
      and the regulatory subunits, A and B. The A and C subunits both exist as 2
      isoforms (alpha and beta) and the B subunit as multiple forms subdivided into 3
      families, B, B' and B". It has been reported that the genes encoding the Aalpha
      and Abeta subunits are mutated in various human cancers, suggesting that they may
      function as tumor suppressors. We investigated whether Aalpha and Abeta mutations
      occur in human gliomas. Using single strand conformational polymorphism analysis
      and DNA sequencing, 58 brain tumors were investigated, including 23
      glioblastomas, 19 oligodendrogliomas and 16 anaplastic oligodendrogliomas. Only
      silent mutations were detected in the Aalpha gene and no mutations in the Abeta
      gene. However, in 43% of the tumors, the level of Aalpha was reduced at least 10
      fold. By comparison, the levels of the Balpha and Calpha subunits were mostly
      normal. Our data indicate that these tumors contain very low levels of core and
      holoenzyme and high amounts of unregulated catalytic C subunit.

PMID- 11519041
TI  - Promoter hypermethylation of MGMT is associated with protein loss in gastric
      carcinoma.
AB  - Aberrant methylation of CpG islands within promoter regions is associated with
      transcriptional inactivation of various tumor suppressor genes in neoplasms.
      Recently, O(6)-methylguanine-DNA methyltransferase, MGMT, was shown to be
      hypermethylated in certain carcinomas, resulting in loss of MGMT protein. We
      studied DNA methylation of CpG islands of the MGMT gene by methylation specific
      PCR in 26 gastric carcinoma tissues and 8 gastric carcinoma cell lines for
      comparison with levels of MGMT protein expression. In addition, we examined p53
      mutation status in the same tissues by PCR-SSCP analysis for comparison with MGMT
      protein expression levels. In total, promoter hypermethylation of the MGMT gene
      was found in 8 (31%) of the 26 gastric carcinomas with reduced expression of MGMT
      protein, whereas the hypermethylation was not detected in the 18 carcinomas with
      non-reduced MGMT expression. MGMT protein expression levels were associated with
      promoter hypermethylation of MGMT (p = 0.0001; Mann-Whitney test); however, MGMT
      expression was not associated with p53 mutation status (p = 0.461; Mann-Whitney
      test). Among in gastric carcinoma cell lines, the TMK-1 cell line showed loss of
      the MGMT protein association with promoter hypermethylation and this loss was
      rectified by treatment with a demethylating agent, 5-Aza-2'-deoxycytidine. Our
      results suggest that transcriptional inactivation of MGMT by aberrant methylation
      of the promoter region may participate in carcinogenesis in the stomach.

PMID- 11519042
TI  - Antagonistic effects of c-myc and Epstein-Barr virus latent genes on the
      phenotype of human B cells.
AB  - Epstein-Barr virus (EBV) immortalized cells and Burkitt lymphoma cells have a
      completely different growth pattern and phenotype. EBV immortalized cells express
      a set of 11 viral genes to accommodate B cell activation and proliferation,
      whereas EBV-positive Burkitt lymphoma cells highly express the c-myc oncogene
      that is activated through translocation into 1 of the immunoglobulin loci and
      EBNA1 as the only viral protein. We have developed a primary human B cell line
      conditionally immortalized by Epstein-Barr virus in which the viral gene program
      responsible for the induction of proliferation can be switched on and off by the
      addition or withdrawal of estrogen (cell line EREB2-5). Starting from this cell
      line we have generated 2 daughter cell lines that proliferate in a c-myc
      dependent fashion, 1 with a highly active exogenous c-myc gene (cell line A1) and
      1 with a regulatable c-myc gene that can be switched on by withdrawal and
      switched off by addition of tetracycline (cell line P493-6). The comparison of
      the 3 cell lines has allowed us to dissect the contribution of c-myc and EBV
      genes to the regulation of the growth pattern and expression of cell surface
      molecules. We show that MYC and EBNA2 (and their respective target genes) have
      opposing effects on the expression of several surface markers involved in B cell
      activation. We show that MYC contributes to the phenotype of Burkitt lymphoma
      cells by upregulating CD10 and CD38 and downregulating activation markers. The
      phenotype of the cells is determined on one hand by the absence of the viral gene
      products EBNA2 and LMP1 that mediate the phenotype of activated lymphoblasts and
      to a lesser extent by an active contribution of the c-myc gene.

PMID- 11519043
TI  - HLA class II alleles associated with infection by HPV16 in cervical cancer in
      situ.
AB  - HLA class II alleles have been associated with an increased risk of developing
      cervical cancer through infection with oncogenic forms of human papilloma virus
      (HPV). We have examined the association of variation at the DRB1 and DQB1 loci
      with HPV16 infection and risk of development of cervical cancer by analysis of
      440 cases diagnosed with cervical cancer in situ and 476 age-matched controls in
      a retrospective case-control study. The infection history of a woman was studied
      by analysis of cervical smears taken at multiple times during a period of up to
      27 years (1969-95). The frequency of a number of alleles are either increased
      (DRB1*0801, DRB1*1501, DQB1*0402 and DQB1*0602) or decreased (DRB1*0101,
      DRB1*1301, DQB1*0501 and DQB1*0603) in the cancer patients compared to the
      controls. After correction for multiple testing, only the DQB1*0602 and the
      DRB1*1501 alleles remain associated with cancer and only in HPV16-infected
      patients (DQB1*0602: 102/264 (39%) vs. 130/476 (28%), p = 0.028 and DRB1*1501:
      104/259 (40%) vs. 132/469 (28%), p = 0.027). These alleles are associated
      primarily with infection by HPV and only indirectly affect the risk of developing
      cervical cancer in situ. To study the impact of these alleles on persistence of
      infection, women with short-term infections were compared to those with long-term
      infections. Carriers of DQB1*0602 and DRB1*1501 were more frequent in the group
      with long-term HPV infections, indicating that these class II alleles contribute
      to the inability to clear an HPV infection.

PMID- 11519044
TI  - Differential sensitivity of human papillomavirus type 16(+) and type 18(+)
      cervical carcinoma cells to CD95-mediated apoptosis.
AB  - When cervical carcinoma cells were monitored for apoptotic signals, HPV18(+)
      lines were found to be highly sensitive to agonistic CD95 antibodies or
      recombinant CD95 ligands after co-exposure with CHX (CD95(S)). In contrast,
      HPV16(+) cervical carcinoma cells and HPV16-immortalized non-malignant human
      keratinocytes were CD95-resistant (CD95(R)) under equivalent conditions. Somatic
      cell hybridization between CD95(S) and CD95(R) cervical carcinoma cell lines
      revealed that CD95 sensitivity was a dominant trait, which could be correlated
      with abundant c-Myc and low Bcl-X(L) expression. Although CD95(R) cervical
      carcinoma cells expressed even higher levels of p53 and CD95 receptor at the
      surface, resistance could be attributed to the inability to form a functional
      DISC, necessary for successful transmission of the apoptogenic response. These
      data indicate that resistance to apoptotic stimuli represents an important
      immunological escape mechanism during virus-induced carcinogenesis.

PMID- 11519045
TI  - Evidence for a bias toward intracellular antigens in the local humoral anti-tumor
      immune response of a colorectal cancer patient revealed by phage display.
AB  - Many patients with colorectal carcinoma (CRC) mount a cellular as well as a
      humoral immune response to the tumor. To investigate the nature and specificity
      of the humoral immune response in a CRC patient, lymphocytes infiltrating the
      primary colorectal tumor and lymph nodes draining the tumor were used as antibody
      variable (V)-gene pools for the construction of phage antibody repertoires. These
      libraries were first validated by selection on the antigen tetanus toxoid and
      shown to contain antibodies that were probably derived from both naive and memory
      B cells. The repertoires were then screened for the presence of antibodies
      directed to CRC by selection on the cell line CaCo2. For comparison, the same
      selections were performed with a phage antibody repertoire made from B cells of
      healthy donors. Striking differences were observed in the panel of specificities
      selected from these different repertoires: although a large panel of antibodies
      reactive with patient-derived primary tumors was obtained from the immune
      repertoires, none of these discriminated between normal colonic epithelium and
      colon cancer and none were reactive with cell-surface antigens. However,
      selections using the non-immune library did result in numerous antibodies that
      recognized cell surface markers on CaCo2. These data suggest a bias in the local
      humoral immune response in this CRC patient, directed primarily toward
      intracellular epithelial-cell specific target antigens.

PMID- 11519046
TI  - Unmasking cryptic epitopes after loss of immunodominant tumor antigen expression
      through epitope spreading.
AB  - The basis of intra-tumoral and systemic T cell reactivity toward cancer remains
      unclear. In particular the role that peripheral stimuli, whether endogenous or
      exogenous, play in shaping acquired immune response toward cancer remains poorly
      understood. In this study we document the surfacing of systemic immune reactivity
      toward a cryptic epitope from the MAGE-12 gene (MAGE-12:170-178), after temporary
      regression of a single melanoma metastasis, in response to gp100/PMel17-specific
      vaccination. This emergence was unlikely related to unusually high expression of
      MAGE-12 by the tumor, by the influence of analog epitopes to MAGE-12:170-178.
      Because MAGE-12 was unlikely to be expressed at sites other than the tumor, the
      demonstration of MAGE-12:170-178 reactivity in post- but not pre-vaccination
      circulating lymphocytes suggests that the systemically observed immune response
      was influenced by events induced by the vaccine at tumor site or draining lymph
      nodal areas. Possibly, as suggested by pre-clinical models, immunologic ignorance
      is the default response toward cancer in humans unless unusual stimulatory
      conditions occur in peripheral tissues. Surfacing of MAGE-12 specificity occurred
      in association with loss of gp100/PMel 17 targeted by the vaccine. This finding
      suggests that vaccinations might have effects beyond their intrinsic specificity
      and may trigger broader immune responses through epitope spreading by inducing
      changes within the tumor microenvironment. This may have important practical
      implication for the development of immunization strategies. Published 2001 Wiley
      Liss, Inc.

PMID- 11519048
TI  - Specific killing of P53 mutated tumor cell lines by a cross-reactive human HLA-A2
      restricted P53-specific CTL line.
AB  - p53 is upregulated in the majority of spontaneous tumors and the HLA class I
      molecule HLA-A2 is expressed by approximately 50% of the caucasians. Potentially,
      these facts make HLA-A2-binding p53 peptides for CTL-inducing immunotherapy
      applicable to a broad range of cancer patients. In our study, we investigated the
      CTL-inducing capacity of autologous monocyte-derived dendritic cells (DC)
      maturated by exposure to CD40L and pulsed with a pool of 4 wild-type, HLA-A2
      binding p53 peptides, and the p53-specific CD8(+) CTL lines established from
      healthy HLA-A2-positive donors were characterized. Reactivity to p53(65-73) and
      p53(187-197) peptides was obtained in the T-cell lines. Interestingly, cold
      target inhibition experiments demonstrated that the simultaneous recognition of
      the 2 peptides was the result of cross-reactivity, which was confirmed by killing
      experiments at the clonal CTL level. Furthermore, 4 HLA-A2(+) p53-mutated tumor
      cell lines were lysed by the CTL line, indicating that these peptides are
      endogenously processed and presented on HLA-A2 molecule. Thus, monocyte-derived
      DC pulsed with a pool of peptides are able to induce CTL reactivity to wild-type
      p53 peptides presented by several cancer cell lines. In addition, the recognition
      of 2 different p53 peptides by the same CTL clone suggests a promiscuous peptide
      recognition by the TCR involved. Taken together, these in vitro results suggest
      that vaccination with autologous DC pulsed with multiple p53 epitopes may induce
      an effective tumor-specific CTL response in vivo with the potential to eradicate
      p53-upregulated spontaneously occurring tumors.

PMID- 11519047
TI  - K562 erythroleukemic cells are equipped with multiple mechanisms of resistance to
      lysis by complement.
AB  - Resistance of tumor cells to lysis by complement is generally attributed to
      several protective mechanisms. The relative impact of these mechanisms in the
      same tumor cell, however, has not been assessed yet. We have analyzed the
      interaction of the human erythroleukemia tumor cell line K562 with human
      complement. K562 cells express the membrane complement regulatory proteins CD59,
      CD55 and CD46. As shown here for the first time, K562 also spontaneously release
      the soluble regulators C1 inhibitor, factor H, and soluble CD59. Complement
      resistance of K562 cells is augmented upon treatment with PMA, TNF or even with
      sublytic complement. Unlike TNF and sublytic complement, PMA enhanced the
      expression of membrane-bound CD55 and CD59 and led to increased secretion of
      soluble CD59. In addition, we show that complement-resistant K562 cells express a
      membrane-associated proteolytic activity, higher than the complement-sensitive
      K562/S cells. Treatment of complement-resistant K562 cells with serine protease
      inhibitors enhance their sensitivity to complement-mediated lysis. Inhibitors of
      protein kinase C (PKC) also sensitize K562 cells to complement lysis, implicating
      PKC-mediated signaling in cell resistance to complement. Neutralization of the
      CD55 and CD59 but not of CD46 regulatory activity with specific antibodies
      significantly increases complement-mediated K562 cell lysis. Treatment of K562
      cells with a mixture of inhibitory reagents results in a significant additive
      enhancing effect on complement-mediated lysis of K562. In conclusion, K562 cells
      resist a complement attack by concomitantly using multiple molecular evasion
      strategies. Future attempts in antibody-based tumor therapy should include
      strategies to interfere with those resistance mechanisms.

PMID- 11519049
TI  - Bone marrow microcirculation analysis in multiple myeloma by contrast-enhanced
      dynamic magnetic resonance imaging.
AB  - The aim of our study was to investigate the quantitative microcirculation
      parameters amplitude A (hypothetical intravascular volume) and exchange rate
      constant k(21) (hypothetical vascular permeability) by contrast-enhanced dynamic
      magnetic resonance imaging (dMRI) as markers of angiogenesis in multiple myeloma
      (MM). Therefore lumbar spine and spina iliaca superior posterior of 16 normal
      controls and 41 patients with active MM were assessed using a dMRI protocol with
      a pump controlled bolus infusion of Gadolinium-DTPA. Pharmacokinetic parameters,
      amplitude A and exchange rate constant k(21) were calculated according to a 2
      compartment model. Color-coded parameter images were generated from
      pharmacokinetic data analysis and superimposed onto the conventional MR images.
      Amplitude A and k(21) parameters were significantly increased in patients with MM
      compared with controls (p = 0.001; median A(ctr), 0.2 [range, 0.09-0.4]; median
      A(MM), 0.93 [range, 0.2-2.2]; median k(21ctr), 0.09 min(-1) [range, 0.03-0.9];
      median k(21MM), 4.58 [range, 0.22-23.8]). Within the group of MM patients the
      pattern of color-coded parameter images were found to be either of "diffuse" (n =
      13, 31%) or "focal" (n = 28, 69%) type of distribution of microcirculation.
      Comparison of amplitude A in patients with "focal" vs. "diffuse" pattern of the
      pharmacokinetic maps revealed a significant increase in the median of amplitude A
      in the "focal" group. Amplitude A values allowed a classification of patients
      according to severe osteolytic bone involvement (p = 0.023) with the best cutoff
      value of 0.7 for amplitude A. Downmodulation of amplitude A was observed in a MM
      patient treated with standard VAD chemotherapy. Our data demonstrate that dMRI is
      a novel imaging technique for the detection and monitoring of MM bone lesions. It
      provides independent evidence for angiogenesis in MM.

PMID- 11519050
TI  - Elevated expression of vacuolar proton pump genes and cellular PH in cisplatin
      resistance.
AB  - V-ATPases are proton-translocating enzymes, which are found not only in numerous
      intracellular organelles but also in the plasma membranes of many eukaryotic
      cells. Using differential display, we have identified one of the proton pump
      subunit genes, ATP6C, as a cisplatin-inducible gene. Northern blot analysis
      demonstrated that expression of other members of the subunit is inducible by
      cisplatin treatment. Proton pump gene expression is also upregulated in 3
      independent cisplatin-resistant cell lines but not in vincristine- or etoposide
      resistant cell lines. Cellular pH was significantly higher in cisplatin-resistant
      cells than in sensitive parental cells. In vitro DNA-binding activity of
      cisplatin was markedly increased in acidic conditions, suggesting that the
      cytotoxicity of cisplatin is modulated by cellular pH. Furthermore, the proton
      pump inhibitor bafilomycin can synergistically potentiate the cytotoxicity of
      cisplatin but not of etoposide or camptothecin. These results indicate that
      cellular pH is one of the critical parameters for effective cancer chemotherapy
      with cisplatin.

PMID- 11519052
TI  - Fluid consumption and the risk of bladder cancer: results of a multicenter case
      control study.
AB  - A number of studies suggest a relation between fluid consumption and the risk of
      bladder cancer but results are contradictory. Different theories involving the
      quantity or the type of fluid consumed have been put forward to explain these
      relations but mechanisms remain unclear. We conducted a multicenter case-control
      study in several hospitals in France including 765 cases and 765 matched
      controls. Information collected by face-to-face interview included quantity and
      type of beverages consumed from the age of 18 until age at diagnosis, as well as
      smoking habits. Among men, we observed a slight non-significant increased risk of
      bladder cancer associated with total fluid intake, irrespectively of tobacco use.
      This was essentially due to intake of non-alcoholic drinks, coffee and bottled
      juice or water. Relative risks greater than 1 were observed in relation with
      coffee consumption. On the other hand, alcohol consumption, especially wine, was
      associated with relative risks less than unity. No relation could be identified
      between bladder cancer risk and fluid consumption among women. Our results do not
      support an association between total fluid consumption and bladder cancer risk.
      The role of the different types of fluid consumed, confounding factors and bias
      in the present analysis are discussed.

PMID- 11519051
TI  - Cell-killing potential of a water-soluble radical initiator.
AB  - The diazo compound, 2,2'-azobis [2-(2-imidazolin-2-yl) propane] dihydrochloride
      (AIPC), is a water-soluble radical initiator that can be activated at mild
      temperatures (37 degrees -40 degrees C). Potential biomedical applications of
      this compound include the fabrication of hydrogels by radical polymerization
      (e.g., cell encapsulation or drug delivery) and the thermal sensitization of
      cancerous cells to induce localized cell death. In this study we evaluated
      whether this compound could induce cell death at 37 degrees C in vitro and in
      vivo using a tumor animal model. Cytotoxicity was quantitated with a sulfo
      rhodamine B colorimetric assay by monitoring growth inhibition of human glioma
      cells in vitro. AIPC was entrapped in fibrin gel and exposed to cells in culture
      as a potential way to localize the compound in a controlled release environment.
      The mechanism of action for cell death was evaluated by quantitating caspase-3
      activity in cells. In vivo studies included human glioma tumors that were grown
      subcutaneously in rats to study the effect of intra-tumor injections of AIPC.
      AIPC was also injected subcutaneously into normal tissue. Concentrations of 0.2%
      and 0.02% (w/v in RPMI medium) showed 93% and 84% inhibition of cell growth in
      vitro, respectively. Cell-growth inhibition using gel-entrapped AIPC was
      comparable to that obtained with AIPC in solution after 48 hr (86% inhibition at
      0.2% w/v). Exposure to AIPC resulted in a significant increase of caspase
      activity (up to 163 units after 20 min), suggesting induced apoptosis as a
      possible mechanism of action of the AIPC. Histological pictures showed that,
      relative to normal tissue, cancerous tissue was more sensitive to the effects of
      AIPC.

PMID- 11519053
TI  - Childhood and adult milk consumption and risk of premenopausal breast cancer in a
      cohort of 48,844 women - the Norwegian women and cancer study.
AB  - Analyses of dairy consumption and breast cancer incidence have yielded
      conflicting results. In this prospective cohort study of 48,844 premenopausal
      Norwegian women, we examined the relationship between childhood and adult milk
      consumption and breast cancer incidence. During a mean follow-up time of 6.2
      years, 317 incident cases of breast cancer were diagnosed. Information on
      childhood and adult milk consumption was obtained from frequency questions mailed
      to the participants in 1991-92. Milk consumption as a child was negatively
      associated with subsequent breast cancer among the youngest women (34-39 years)
      (p for trend = 0.001), but not among older ones (40-49 years). Adult milk
      consumption tended to be negatively related to breast cancer incidence (p for
      trend = 0.12) after adjustment for age, reproductive and hormonal factors, body
      mass index, education, physical activity, and alcohol consumption. Women drinking
      more than 3 glasses of milk per day had an incidence rate ratio of breast cancer
      of 0.56 (95% confidence interval 0.31-1.01) compared with women not drinking
      milk. Analyses according to type of milk consumed and milk fat consumption did
      not reveal any clear associations. A combination of childhood and adult milk
      consumption produced a clear negative trend in breast cancer incidence rate
      ratios with increasing milk consumption (p = 0.03).

PMID- 11519054
TI  - Differences in stage and therapy for breast cancer across Europe.
AB  - We examined variations in stage, diagnostic workup and therapy for breast cancer
      across Europe. Seventeen cancer registries in six European countries contributed
      4,480 cases diagnosed in 1990-91. The clinical records of these cases were
      examined, and the distribution of stage, diagnostic examinations and therapy were
      analyzed. Stage was earliest in the French registries, followed by those of Italy
      and Eindhoven (Netherlands). The proportion of stage I cancers was highest in the
      French areas with screening in place. Estonia, the English registries and Granada
      (Spain) had the most advanced stage at diagnosis. Use of liver ultrasonography
      varied from 84% (Italian registries) to 18% (Granada). Bone scan use varied from
      81% (Italian registries) to 15% (Mersey, UK). The highest proportions treated by
      breast-conserving surgery were in the French (57%) and English registries (63%);
      the lowest were in Estonia (6%) and Granada (11%). The highest proportions of
      Halsted mastectomies were in Italy (19%) and Granada (8%). In all countries
      except England, 90% of operations included axillary lymphadenectomy. Medical
      treatment only was given to 8% of (mostly advanced) cases overall. Estonia (21%)
      and the English registries (14%) had the highest proportions of patients given
      medication only. Chemotherapy was given to low proportions of node-positive cases
      in the Italian (76%) and English (74%) areas; breast-conserving surgery for stage
      I tumors varied from 24% in Granada to 84% in England. These wide differences in
      breast cancer care across Europe in the early 1990s indicate a need for continual
      monitoring of past treatments to help ensure application of the most effective
      protocols.

PMID- 11519055
TI  - Lifetime residential and workplace exposure to environmental tobacco smoke and
      lung cancer in never-smoking women, Canada 1994-97.
AB  - Although the risk of lung cancer among never-smokers living with a spouse who
      smokes has been extensively studied, the impact of lifetime residential and
      workplace environmental tobacco smoke has received less attention. As part of a
      large population-based case-control study of lung cancer, we collected lifetime
      residential and occupational passive smoking information from 71 women with lung
      cancer and 761 healthy control subjects, all of whom reported being lifetime
      nonsmokers. The adjusted odds ratio (OR) for lung cancer associated with
      residential passive exposure only was 1.21 (95% confidence interval [CI] 0.5
      2.8). Although more years of and more intense residential passive smoke exposure
      tended to be associated with higher risk estimates, no clear dose-response
      relationship was evident. The OR for women with passive exposure as a child and
      as an adult was 1.63 (95% CI 0.8-3.5) and for those only exposed as an adult 1.20
      (95%CI 0.5-3.0). Exposure to environmental tobacco smoke only in the workplace
      was associated with an adjusted OR of 1.27 (95% CI 0.4-4.0). Risks associated
      with increasing occupational exposure year tertiles were 1.24, 1.71 and 1.71.
      Total smoker-years of residential and occupational exposure combined resulted in
      a statistically significant trend (linear test for trend p = 0.05) with ORs for
      tertiles of exposure of 0.83, 1.54 and 1.82. Our results are consistent with the
      literature suggesting that long-term, regular exposure to either residential or
      occupational environmental tobacco smoke is associated with increased lung cancer
      risk in never-smoking women.

PMID- 11519056
TI  - Breast cancer risk in women who have had children with different partners.
AB  - The fetal antigen hypothesis suggests that the lowered risk of breast cancer in
      parous women may be afforded by the development of antibodies to fetal antigens
      that are structurally similar to mammary cancer antigens. It has previously been
      hypothesized that the likelihood of developing such antibodies may be higher
      among women who have had children with more than 1 partner. Utilizing information
      on parenthood and breast cancer available in nationwide Swedish registers, we
      undertook a case-control study nested within a nation-wide cohort to address this
      issue. Number of partners fathering a child was categorized as 1, 2 and 3 or
      more. All analyses were restricted to subjects with 2 or more births and
      encompassed a total of 20,881 women with breast cancer and 111,989 control women.
      In an unadjusted analysis, the risk of breast cancer was somewhat lower (odds
      ratio [OR] = 0.94, 95% confidence interval [CI] 0.89-0.99) in women who had had
      children with 2 different partners compared with women who had had children
      conceived with the same partner. After adjustment for parity, age at first birth
      and educational level, however, the risk of breast cancer was slightly elevated
      (OR = 1.09, 95% CI: 1.03-1.15). Among women who had had children with 3 or more
      different men, the pattern was similar. The present results provide no support
      for the hypothesis that greater antigenic exposure afforded by having children
      with more than 1 man may reduce the risk of breast cancer. It remains possible,
      however, that pregnancy may influence breast cancer risk through some immunologic
      mechanism; further testing of the fetal antigen hypothesis may require
      development of relevant laboratory measures.

PMID- 11519057
TI  - Diet and ovarian cancer risk: a case-control study in Italy.
AB  - To assess the dietary correlates of cancer of the ovary, the consumption of a
      wide range of food groups has been investigated in a case-control study conducted
      between January 1992 and September 1999 in 4 Italian areas. Cases were 1,031
      women with incident, histologically confirmed epithelial ovarian cancer; controls
      were 2,411 women admitted to the same network of hospitals as the cases for
      acute, non-malignant and non-gynecological conditions, unrelated to hormonal or
      digestive tract diseases or to long-term modifications of diet. The subjects'
      usual diet was investigated through a validated food frequency questionnaire
      including 78 foods and recipes, then grouped into 18 food groups. Odds ratios
      (OR), and the corresponding 95% confidence intervals (CI) were estimated using
      unconditional multiple logistic regression models including terms for age, study
      center, education, year at interview, parity, oral contraceptive use and energy
      intake. Significant trends of increasing risk emerged for red meat (OR = 1.53 for
      the highest compared with the lowest quintile of consumption), whereas inverse
      associations were observed for consumption of fish (OR = 0.51), raw (OR = 0.47)
      and cooked vegetables (OR = 0.65), and pulses (OR = 0.77).

PMID- 11519059
TI  - Minimally-invasive approaches to the treatment of breast cancer.

PMID- 11519060
TI  - Do surgical oncologists achieve lower rates of local-regional recurrence in node
      positive breast cancer treated with mastectomy alone?
AB  - BACKGROUND AND OBJECTIVE: Adjuvant radiotherapy for node positive breast cancer
      postmastectomy has been recommended by two previously published randomized
      controlled trials (RCT). The local-regional recurrence rates in the control arms,
      however, were considered by some critics to be excessive (> 25% at 10 years).
      Inadequate surgery, as evidenced by the low number of axillary nodes reported,
      may have resulted in the high local-regional recurrence rates, allowing for the
      benefits seen with radiotherapy. Fellowship trained surgical oncologists might
      provide "better quality" surgery, resulting in lower recurrence rates and thus
      making adjuvant radiotherapy unnecessary. Our objective was to establish the
      local-regional control rate postmastectomy in node positive breast cancer
      patients operated on by surgical oncologists, and to determine if treatment
      recommendations from previous RCTs are generalizable. METHODS: Node positive
      stage IIb and IIIa breast cancer patients treated with mastectomy at the Medical
      College of Virginia Hospitals by surgical oncologists, without adjuvant
      radiotherapy, and entered into adjuvant chemotherapy trials between 1978 and 1993
      were identified retrospectively. Pathology and follow-up records were reviewed.
      RESULTS: One hundred and thirty-seven patients were identified. A median of 18
      axillary nodes was reported with a median of 4 positive nodes. The locoregional
      recurrence at 10-years was 27% (95% confidence interval, 19-35%). CONCLUSION:
      Despite some evidence of "better quality" surgery, there was no clinically
      significant difference in the local-regional recurrence rate in this case series
      compared to controls in two previous RCTs. Recommendations for postmastectomy
      radiotherapy should be considered for node positive breast cancers, even if
      operated upon by surgical oncologists.

PMID- 11519062
TI  - Melanoma in African-Americans: trends in biological behavior and clinical
      characteristics over two decades.
AB  - BACKGROUND: The incidence of melanoma in the United States is increasing. Data on
      this disease in African-Americans is sparse. METHODS: Chart review of patients
      diagnozed with melanoma from 1975 to 1997 at Charity Hospital New Orleans (CHNO).
      Age, gender, anatomic distribution, histology, presenting stage, survival, and
      race were evaluated. RESULTS: Forty-four of 198 patients were African-American,
      of whom the majority developed cutaneous melanoma on the acral surface of the
      foot. African-American males were four times more likely to present with a
      cutaneous lesion than were African-American females. The median survival time for
      African-American with cutaneous lesions was 45 months, compared to 135 months for
      caucasians who were 3.6 times more likely to present with early disease (P <
      0.05). TNM stage at presentation, and ulceration were significant, independent
      factors associated with a worse outcome in African-Americans. CONCLUSION: Overall
      survival time for African-Americans with cutaneous melanoma is significantly
      shorter than for caucasians with this disease. This trend may be attributable to
      the fact that African-Americans present with advanced disease. An increased level
      of awareness among both patients and health-care providers is necessary to
      identify African-Americans with melanoma at earlier stages of disease and to
      improve survival.

PMID- 11519063
TI  - Combined colon and hepatic resection for synchronous colorectal liver metastases.
AB  - BACKGROUND AND OBJECTIVES: The surgical strategy for the treatment of resectable
      synchronous hepatic metastases of colorectal cancer remains controversial. This
      study was performed to assess the outcome of combined resection of colorectal
      cancer and liver metastases. METHODS: The perioperative data, morbidity, and
      survival of the patients who underwent combined colon and liver resections for
      synchronous colorectal liver metastases from 1988 to 1999 were compared to the
      parameters of the patients who underwent colon resection followed by resection of
      liver metastases in a staged setting. RESULTS: 198 hepatic resections were
      performed, of which 112 procedures in 103 patients were done for metastatic
      colorectal carcinoma. Twenty six patients (25%) had combined hepatic and colon
      resection and were compared to 86 patients with metachronous metastases who
      underwent colon and hepatic resection in the staging setting. Postoperative
      morbidity was 27 and 35%, respectively. There was no hospital mortality in the
      combined group vs. 2.3% in the staged group. Blood loss, intensive care unit
      (ICU) stay and length of postoperative stay (LOS) were similar in both groups.
      The 5 years cumulative survival of the group after combined surgery was 28% vs.
      27% of the group after isolated hepatic resections (P = 0.21). CONCLUSION:
      Combined colon and hepatic resection is a safe and efficient procedure for the
      treatment of synchronous colorectal liver metastases. It can be performed with
      acceptable morbidity and no perioperative mortality. The survival after combined
      procedure is comparable to the one achieved after staged procedure of colon
      resection followed by liver resection.

PMID- 11519064
TI  - Targeting liver tumors with hyperthermia: ferromagnetic embolization in a rabbit
      liver tumor model.
AB  - BACKGROUND AND OBJECTIVES: Ferromagnetic embolization hyperthermia (FEH) consists
      of arterially embolizing liver tumors with ferromagnetic particles, and then
      applying an external alternating magnetic field to generate hysteretic heating
      within the embolized particles. The objective of this study was to assess the
      ability of FEH to selectively target liver tumors with hyperthermia. METHODS:
      Twenty rabbits containing hepatic VX2 carcinomas were arterially infused with
      ferromagnetic particles suspended in lipiodol, and then exposed to an external
      alternating magnetic field. Temperatures in the tumor, normal hepatic parenchyma
      (NHP), and rectum were recorded. Tumour and NHP were chemically analyzed for iron
      content, which was then correlated with the observed heating rates. RESULTS: The
      mean tumor-to-NHP iron concentration ratio was 5.3:1 (P < 0.001, N = 20). The
      mean tumor heating rates were 3.0-11.5 times greater than those in the NHP (P <
      0.001, N = 20). After 5 min of heating, the greatest increase in mean tumor
      temperature was 11.0 degrees C and the greatest increase in mean NHP temperature
      was 1.3 degrees C. There was a positive relationship between tumor iron
      concentration and heating rate (correlation coefficient = 0.82, P < 0.001, N =
      20). A tumor iron concentration of 2-3 mg/g resulted in tumor heating rates of
      0.5-1.0 degrees C/min. CONCLUSIONS: Hepatic arterial infusion of lipiodol
      containing ferromagnetic particles can result in excellent targeting of liver
      tumors with hyperthermia on the subsequent application of an external alternating
      magnetic field. The promising results of this study warrant further investigation
      of FEH as a potential treatment for advanced liver cancer.

PMID- 11519066
TI  - Phase IB study on prevention of surgery-induced immunodeficiency with
      preoperative administration of low-dose subcutaneous interleukin-2 in gastric
      cancer patients.
AB  - BACKGROUND AND OBJECTIVES: Low count of total and T helper lymphocytes predicts a
      poor prognosis in cancer patients and surgical trauma can worsen cancer-related
      immunodeficiency. Aim of this phase IB study is to verify toxicity and biological
      effects of interleukin-2 (IL-2) at 9 million IU/day subcutaneously (sc.)
      administered one, two or three preoperative days in patients with gastric cancer
      undergoing radical surgery. METHODS: Absolute value of total and T-helper (CD4)
      lymphocytes were measured at baseline and at 7th, 14th, and 50th postoperative
      days in 12 gastric cancer patients, who preoperatively received IL-2 at 9 million
      IU/day sc. as follows: group A (4 pts) 1-day; group B (4 pts) 2-days; group C (4
      pts) 3-days administration. T and total lymphocytes count were recorded and
      retrospectively analyzed in a historical control-group of 22 consecutive
      patients, age and stage-matched. RESULTS: Toxicity consisted of fever grade I. In
      group A (1 day) T helper lymphocytes count decreased at 7th and at 14th
      postoperative day; in group B (2 days) and group C (3 days) no decrease of
      neither total nor T helper lymphocyte count occurred postoperatively, whereas in
      the historical group these parameters decreased significantly postoperatively and
      recovered only at 50th day. CONCLUSIONS: Two- and three-day schedules of sc. IL-2
      preoperative administration at 9 million IU/daily prevented postoperative
      lymphocytopenia, whereas one-day administration did not. Since the IL-2 dose was
      so tolerable, that it could be given safely as outpatient, based on the previous
      results on survival observed in colorectal cancer patients with 3-days schedule
      we suggest that a 3-day schedule of Interleukin-2 as outpatient preoperative
      treatment seems advisable for further studies in gastric cancer patients.

PMID- 11519072
TI  - Insect G protein-coupled receptors and signal transduction.
AB  - G protein-coupled receptors (GPCRs) are seven-transmembrane proteins (7-TM) that
      transduce extracellular signals into cellular physiological responses through the
      activation of heterotrimeric guanine nucleotide binding proteins (alpha beta
      gamma subunits). Their general properties are remarkably well conserved during
      evolution. Despite this general resemblance, a large variety of different signals
      are mediated via this category of receptors. Several GPCR-(sub)families have an
      ancient origin that is situated before the divergence of Protostomian and
      Deuterostomian animals. Nevertheless, an enormous diversification has occurred
      since then. The availability of novel sequence information is growing very
      rapidly as a result of molecular cloning experiments and of metazoan genome
      (Caenorhabditis elegans, Drosophila melanogaster, Homo sapiens) and EST
      (expressed sequence tags) sequencing projects. The Drosophila Genome Sequencing
      Project will certainly have an important impact on insect signal transduction and
      receptor research. In parallel, convenient expression systems and functional
      assay procedures will be needed to investigate insect receptor properties and to
      monitor the effects of natural and artificial ligands. The study of the
      evolutionary aspects of G protein-coupled receptors and of their signaling
      pathways will probably reveal insect-specific features. More insight into these
      features may result in novel methods and practical applications. Arch.

PMID- 11519073
TI  - Molecular and pharmacological properties of insect biogenic amine receptors:
      lessons from Drosophila melanogaster and Apis mellifera.
AB  - In the central nervous system (CNS) of both vertebrates and invertebrates,
      biogenic amines are important neuroactive molecules. Physiologically, they can
      act as neurotransmitters, neuromodulators, or neurohormones. Biogenic amines
      control and regulate various vital functions including circadian rhythms,
      endocrine secretion, cardiovascular control, emotions, as well as learning and
      memory. In insects, amines like dopamine, tyramine, octopamine, serotonin, and
      histamine exert their effects by binding to specific membrane proteins that
      primarily belong to the superfamily of G protein-coupled receptors. Especially in
      Drosophila melanogaster and Apis mellifera considerable progress has been
      achieved during the last few years towards the understanding of the functional
      role of these receptors and their intracellular signaling systems. In this
      review, the present knowledge on the biochemical, molecular, and pharmacological
      properties of biogenic amine receptors from Drosophila and Apis will be
      summarized. Arch.

PMID- 11519074
TI  - Pharmacological characterization of STKR, an insect G protein-coupled receptor
      for tachykinin-like peptides.
AB  - STKR is a G protein-coupled receptor that was cloned from the stable fly,
      Stomoxys calcitrans. Multiple sequence comparisons show that the amino acid
      sequence of this insect receptor displays several features that are typical for
      tachykinin (or neurokinin, NK) receptors. Insect tachykinin-related peptides,
      also referred to as "insectatachykinins," produce dose-dependent calcium
      responses in Drosophila melanogaster Schneider 2 cells, which are stably
      transfected with this receptor (S2-STKR). These responses do not depend on the
      presence of extracellular Ca(2+)-ions. A rapid agonist-induced increase of
      inositol 1,4,5-trisphosphate (IP(3)) is observed. This indicates that the agonist
      induced cytosolic Ca(2+)-rise is caused by a release of Ca(2+) ions from
      intracellular calcium stores. The pharmacology of STKR is analyzed by studying
      the effects of the most important antagonists for mammalian NK-receptors on STKR
      expressing insect cells. The results show that spantide II, a potent substance P
      antagonist, is a real antagonist of insectatachykinins on STKR. We have also
      tested the activity of a variety of natural insectatachykinin analogs by
      microscopic image analysis of calcium responses in S2-STKR cells. At a
      concentration of 1 microM, almost all natural analogs produce a significant
      calcium rise in stable S2-STKR cells. Interestingly, Stc-TK, an insectatachykinin
      that was recently discovered in the stable fly (S. calcitrans), also proved to be
      an STKR-agonist. Stc-TK, a potential physiological ligand for STKR, contains an
      Ala-residue (or A) instead of a highly conserved Gly-residue (or G). Arch.

PMID- 11519076
TI  - Radiologic laryngeal parameters in acute supraglottitis in Korean adults.
AB  - Soft-tissue lateral neck radiography is important for diagnosing acute
      supraglottitis. This study aimed to determine the objective criteria for a
      diagnosis of acute supraglottitis from soft-tissue lateral neck radiographs in
      Korean adults. The parameters in 30 adult patients with acute supraglottitis were
      compared with those of age- and sex-matched normal 30 Korean adults. The mean of
      epiglottis width (EW) and aryepiglottic fold width (AEW) in the control group
      were 4.37 +/- 0.93 mm, 2.45 +/- 0.71 mm, respectively and in the patient group
      they were 15.87 +/- 3.60 mm, 6.4 +/- 2.55 mm, respectively. The sensitivity and
      specificity of an EW greater than 7 mm were 100%, and 100% respectively. The
      sensitivity and specificity of an AEW greater than 4.5 mm were 83%, and 100%
      respectively.

PMID- 11519077
TI  - Epidemiological significance of sero-positive inhabitants against sparganum in
      Kangwon-do, Korea.
AB  - Sparganum is a plerocercoid of pseudophyllidean tapeworms, Diphyllobothrium or
      Spirometra spp. Human sparganosis is endemic mainly in East and Southeast Asian
      countries where the custom of eating raw snake or frog meat, or poulticing with
      snake's skin exists. From January 1995 to November 1999, an epidemiological
      survey was undertaken to evaluate the serum levels of anti-sparganum specific IgG
      antibodies in Whachon-gun residents, Korea. An enzyme- linked immunosorbent assay
      (ELISA) and immunoblot analysis of the sera from 316 subjects were used. In
      addition, a stool examination from 416 inhabitants and questionnaires regarding
      the consumption of raw meat were given. Out of 416 inhabitants examined
      coprologically, one was infected with Clonorchis sinensis and two were infected
      with Metagonimus spp. The sera from 36 inhabitants (11.4 %) showed a positive
      reaction to the sparganum antigen. Out of these 36 inhabitants, the sera from 25
      people were examined 7, 19, and 50 months later. The sera were found to still
      show positive reactions without any remarkable changes of anti-sparganum specific
      antibody titers except for one. An analysis of the questionnaires suggested that
      a history of eating of raw snakes or frogs was important risk factor for clinical
      or covert sparganosis (odd ratio=15.6 and 3.1, respectively).

PMID- 11519078
TI  - Hemodynamic effects on atherosclerosis-prone coronary artery: wall shear
      stress/rate distribution and impedance phase angle in coronary and aortic
      circulation.
AB  - The objective of the present study was to evaluate the hemodynamic
      characteristics of an atherosclerosis-prone coronary artery compared to the
      aorta. We describe three- dimensional spatial patterns of wall shear stress (WSS)
      according to the impedance phase angle in pulsatile coronary and aorta models
      using in vivo hemodynamic parameters and computed numerical simulations both
      qualitatively and quantitatively. Angiography of coronary arteries and aortas
      were done to obtain a standard model of vascular geometry. Simultaneously to the
      physiologic studies, flow-velocity and pressure profiles from in vivo data of the
      intravascular Doppler and pressure wire studies allowed us to include in vitro
      numerical simulations. Hemodynamic variables, such as flow-velocity, pressure and
      WSS in the coronary and aorta models were calculated taking into account the
      effects of vessel compliance and phase angle between pressure and flow waveforms.
      We found that there were spatial fluctuations of WSS and in the recirculation
      areas at the curved outer wall surface of the coronary artery. The mean WSS of
      the calculated negative phase angle increased in the coronary artery model over
      that in the aorta model and the phase angle effect was most prominent on the
      calculated amplitude of WSS of the coronary artery. This study suggests that the
      rheologic property of coronary circulation, such as the fluctuation of WSS/WSR
      induces several hemodynamic characteristics. A separation of flow-velocity, a
      difference in phase between pressure conductance and blood flow and prominent
      temporal and/or spatial oscillatory fluctuations of the shear forces as a
      function of pulsatile flow might be important factors in atherogenesis and
      progression of atherosclerosis.

PMID- 11519079
TI  - Acute effect of ethanol on firing patterns of Purkinje cells in the rat
      cerebellar slice preparation.
AB  - This study examined the acute effects of ethanol (EtOH) on the firing patterns of
      Purkinje cells (PCs) using an intracellular recording in slice preparation of rat
      cerebellum. The experiments were performed in sagittal cerebellar slices (400
      micrometer) of adult Sprague-Dawley rats (80-100g). Ethanol was applied by a bath
      superfusion with a known concentration expressed as the percentage of solution by
      volume (v/v) at 0.1, 0.5, 1, 2, and 4%. The result of the Chi-square test
      illustrated that the firing patterns were altered significantly after EtOH
      (p=0.007). However, the firing patterns that were altered by EtOH application
      were not affected by EtOH concentration (p= 0.1296). Among the 54 PCs tested, 30
      PCs did not display any spontaneous firing activity and 24 PCs displayed
      spontaneous spike activity, either spiking in the simple manner (n=14) or
      cyclicly oscillating (n=10). In the presence of EtOH, 31 PCs were quiet, 22 PCs
      exhibited simple spiking activity and 1 PC continued to oscillate. Most PCs that
      displayed spontaneous activity before EtOH application progressively slowed their
      spike activity after EtOH superfusion. Especially, it was evident that 9 out of
      10 oscillating PCs stopped their regular cyclic activity. In addition, 9 out of
      14 PCs that displayed simple spike activity ceased to fire after EtOH
      application. Eleven out of 30 quiet PCs began to fire irregularly after EtOH
      application and this phenomenon usually occurred with membrane depolarization.
      EtOH induced spontaneous activity in 36.7% (11/30) of the quiescent PCs. In
      conclusion, there was differential EtOH sensitivity in the vitro slice
      preparation. EtOH depressed the endogenously generated spontaneous activity,
      especially the oscillatory firing activity. In contrast, the silent PCs were
      excited after EtOH application. Since this differential sensitivity persists in
      the presence of tetrodotoxin (TTX), it is suggested that this differential
      sensitivity is peculiar to the PCs.

PMID- 11519080
TI  - Clinical usefulness of magnetic resonance cisternography in patients having
      hemifacial spasm.
AB  - To evaluate the usefulness of MR cisternography fourteen patients that had
      hemifacial spasm and 20 control patients underwent MR cisternography. All the
      patients with hemifacial spasm had a confirmed vascular compression after
      surgery. MR cisternography was performed using a 1.5-tesla superconducting MR
      magnet in which a 3D (dimensional) heavily T2-weighted turbo spin-echo sequence
      was used. In 34 randomly selected individuals, we retrospectively determined
      whether MR cisternography images could be used to evaluate symptoms, and what the
      benefits of obtaining this image was. The results were correlated with the
      surgical findings. The sensitivity was 100% and the specificity was 94% in all
      patients having a hemifacial spasm. The offending vessels were the anterior
      inferior cerebellar artery (AICA) in six patients cases, the posterior inferior
      cerebellar artery (PICA) in six, both the vertebral artery and PICA in one, and
      the vertebral artery in one. All the images showed good resolution and contrast,
      and also showed the exact correlation between the facial nerve and intracranial
      vessels in the multiplaner image. The findings of neurovascular compression were
      well correlated with the surgical findings. We believe that high-resolution 3D MR
      cisternography is a very useful method for evaluating the neurovascular
      compression in patients that have hemifacial spasm.

PMID- 11519081
TI  - Development of rat prostatitis model by oral administration of isoflavone and its
      characteristics.
AB  - Inflammation of the prostate can be induced experimentally in rats by the
      subcutaneous administration of estrogen. However, it is usually achieved at the
      price of some alteration in the sex steroid hormone balance and morphological
      changes in the prostate. In this study, a soy-extracted isoflavone mixture with
      weak estrogenic activity was administered orally in an attempt to induce
      prostatitis in a more physiologic way and to characterize the inflammation
      induced. A total of 36 male Sprague-Dawley rats, 8 weeks old, were divided into 2
      groups. The control group was fed with only an AIN-76A diet containing no
      detectable phytoestrogen and the experimental group was fed with AIN-76A and a
      soy- extracted isoflavone mixture (genistein 60.0% and daidzein 19.6%), 300 mg/kg
      body weight for 9 weeks. The sequential body weight and prostate weight at
      necropsy were measured. A histologic examination and histomorphometry assessed
      the changes in the prostate. The serum concentrations of testosterone and
      dihydrotestosterone were measured to estimate the effects on the androgen level.
      Intraprostatic concentrations of genistein and daidzein were measured by gas
      chromatography/ mass spectroscopy (GC/MS). While no sign of prostate inflammation
      was apparent in the control group, severe inflammatory changes in the stroma,
      increased epithelial detachment and inflammatory exudates within the glandular
      lumen of the dorsolateral prostate were observed in more than 80%(15/18) of the
      experimental group. However, there was no significant difference in the ventral
      prostate between the two groups. The daidzein and genistein concentrations in
      both the lateral and ventral prostates were significantly higher in the
      experimental group than in the control group where no isoflavone was detectable.
      In addition, the concentrations were much higher in the dorsolateral than in the
      ventral prostate. Although the body weight gain was not consistent in the
      experimental group, there were no significant differences in the prostate weight
      and serum androgen level between groups. In summary, when a soy-extracted
      genistein and daidzein-rich isoflavone mixture was administered orally into rats,
      prostatic inflammation with characteristic lobe specificity developed. The
      present method of inducing prostatitis seems to be a more physiologic than an
      estrogen-induced experimental model, and sequential pharmacokinetic studies might
      help in establishing this model as a more valuable tool in assisting future
      research in this field.

PMID- 11519082
TI  - Effect of centrifugal force on cellular activity of osteoblastic MC3T3-E1 cells
      in vitro.
AB  - The effects of centrifugal force on growth and differentiation of osteoblastic
      cells cultured in alpha-MEM containing 1% Fetal bovine serum were investigated by
      assays of DNA synthesis, alkaline phosphatase activity and osteocalcin-production
      in osteoblastic MC3T3-E1 cells. Centrifugation of the cells in low concentrations
      (1%) of fetal bovine serum caused a 1.9-fold increase of [3H]thymidine
      incorporation on day 3 from the start of centrifugation, and gradually decreased
      with culture up to day 9. Alkaline phosphatase activity was not affected by
      centrifugal force until day 5, and increased rapidly after day 7. Stimulation of
      DNA synthesis by centrifugation was abolished in the presence of H-7, an
      inhibitor of protein kinase C. These results suggest that centrifugal force
      stimulates the proliferation of osteoblastic cells through an autocrine secretion
      of some diffusable growth- promoting activity. Additional centrifugation of the
      cells also slightly stimulated alkaline phosphatase activity, although this did
      not directly influence the cell's osteocalcin-production activity.

PMID- 11519083
TI  - Sonographic findings of metastatic disease to the thyroid.
AB  - The goal of this study was to evaluate the sonographic findings of thyroid
      metastases arising from non-thyroid primaries. The study over a 5-year period
      comprised nine patients who had histopathologically proven metastatic disease to
      the thyroid. Ultrasonography was available in all cases. Ultrasound-guided needle
      aspiration was performed on 10 suspected nodules as determined by ultrasound. The
      Ultrasonographic findings were analyzed in two different ways. The first analysis
      included only those nodules biopsed, and the second analysis included all the
      nodules, biopsed and non-biopsed. The primary neoplasms were breast carcinoma
      (n=6), uterine leiomyosarcoma (n=1), cervical carcinoma (n=1), and nasopharyngeal
      carcinoma (n=1). Excluding 2 nodules, the 8 remaining metastatic nodules
      exhibited ill-defined hypoechoic character with heterogeneous texture. The other
      two nodules showed relatively circumscribed iso- or hypo-echoic character with
      cystic portion. From the analysis of ultrasonographic findings including all
      thyroid nodules irrespective of pathologic proof, 7 cases - excluding the 2 cases
      from the 9 cases - showed unilateral or bilateral multiple nodules suspected of
      metastasis. There was no evidence of microcalcification in any thyroid nodules.
      In conclusion, the sonographic findings of the thyroid metastatic nodules were
      not specific, but unilateral or bilateral multiple suspected thyroid nodules
      without evidence of microcalcification may be suggestive of metastatic nodules
      among patients with a known primary non-thyroidal tumor.

PMID- 11519084
TI  - The diagnostic value of magnetic resonance imaging in subacromial impingement
      syndrome.
AB  - The aim of this study was to assess the diagnostic ability of magnetic resonance
      imaging (MRI) in subacromial impingement syndrome (SIS), using a physiological
      standard of reference. MRI of the rotator cuff (RC) and subacromial injection
      test (SIT), a reference standard for SIS diagnosis, were performed in 125 painful
      shoulders. MRI diagnostic accuracies were determined using a 2 x 2 table and the
      percentage values of SIS diagnosis in patients with the three Zlatkin MRI stages
      were determined. Shoulder function was evaluated using the Constant Scale, and
      results were compared for stages. The sensitivity, specificity, accuracy,
      positive and negative predictive values of MRI for SIS diagnosis were 98.85%,
      36.84%, 80%, 78.18% and 93.33% respectively. Of the 32 patients with Zlatkin
      stage 1 changes in MRI, 20 (62%) had SIT approved SIS diagnosis, while 47 (79%)
      of the 59 patients with Zlatkin 2 and all of the 19 (100%) patients with Zlatkin
      3 changes were diagnosed with SIS by SIT. Mean Constant scores were 78.04 +/-
      18.3, 65.0 +/- 19.9 and 54.52 +/- 20.7 in patients with Zlatkin stages 1, 2 and
      3, respectively (p < 0.05). The MRI of RC did not prove to be an excellent tool
      for SIT based SIS diagnosis, with its low specificity. However, the technique can
      give important clues, as its sensitivity and negative predictive values are high.

PMID- 11519085
TI  - Fatal pulmonary-renal syndrome manifested with immune complex crescentic
      glomerulonephritis in a patient with MPO-ANCA seropositivity.
AB  - Recent reports have indicated that a significant number of immune complex
      glomerulonephritis (GN) cases are associated with antineutrophilic cytoplasmic
      antibody (ANCA). However, most of the reported cases were associated with
      underlying primary glomerular diseases. When primary glomerular diseases were not
      found, immune deposits tended to be non-specific and the level of ANCA is usually
      borderline. We report here upon a case of life-threatening pulmonary-renal
      syndrome manifested simultaneously with immune complex GN and myeloperoxidase
      (MPO)-ANCA seropositivity. A 29- year-old man was admitted with pulmonary
      hemorrhage and rapidly progressing renal dysfunction. On admission, ANCA revealed
      perinuclear staining with a titer of 1:160. The MPO-ANCA level was 59 IU by
      ELISA. Other serologic markers including ANA, anti-DS-DNA and anti-GBM Ab were
      negative. Renal biopsy showed cellular crescents in eight of 18 glomeruli.
      Immunofluorescence staining showed strong granular deposits of C3, C1q, IgG and
      IgM in the capillary loop and the mesangium. Electron microscopy showed
      multifocal electron dense deposits scattered in the mesangium, paramesangium, and
      the subendothelial and subepithelial areas. The patient initially responded to
      steroid and cyclophosphamide. MPO-ANCA decreased to less than 10 IU. Twenty three
      days after hospital discharge, the patient was re-admitted urgently with fever,
      generalized papulonodular skin lesions, and a recurrence of massive pulmonary
      hemorrhage and renal dysfunction. He died from uncontrolled pulmonary hemorrhage
      and respiratory insufficiency. P-ANCA titer and MPO-ANCA level at the second
      admission were 1:320 and 82 U/ml respectively. Interestingly, relapse was shown
      to be triggered by varicella zoster infection.

PMID- 11519086
TI  - Teratoid hepatoblastoma: multidirectional differentiation of stem cell of the
      liver.
AB  - Hepatoblastoma is the most common malignant hepatic neoplasm of childhood,
      showing a wide spectrum of epithelial and mesenchymal components. Teratoid
      hepatoblastoma, which reveals multiple lines of tissue differentiation such as
      mucinous epithelium, melanin pigment, endocrine differentiation, glial and
      mesenchymal components, has rarely been observed. We report a case of teratoid
      hepatoblastoma in a 22-month-old girl. She had been diagnosed with hepatoblastoma
      through percutaneous needle biopsy of the liver and treated with 10 chemotherapy
      cycles of epirubicin, VP-16 and cisplatin and with hepatic artery embolization.
      After 10 months, an extended left lobectomy was performed. Grossly, a
      multinodular, partly well-demarcated, solid mass (7 x 5 cm) with dense fibrosis
      and focal cystic change occupied almost the entire specimen. There was extensive
      necrosis due to preoperative treatment. Microscopically, the tumor showed
      multiple lines of differentiation, which was composed of embryonal, fetal
      hepatocytes and mesenchymal elements with numerous foci of osteoid. There were
      also other components showing endodermal, neural, melanocytic and endocrine
      differentiation. These teratoid components were considered relatively resistant
      to preoperative chemotherapy, in contrast to extensive necrosis of both embryonal
      and fetal hepatocytes. These teratoid features of hepatoblastoma are considered
      to be a multidirectional differentiation of the small epithelial cells or stem
      cells of the tumor.

PMID- 11519087
TI  - Postinfarction left ventricular rupture misdiagnosed ruptured intramural hematoma
      of aorta.
AB  - Left ventricular rupture is a fatal complication of acute myocardial infarction,
      however accurate preoperative diagnosis is still difficult. We experienced a
      postinfarction left ventricular rupture patient whose symptoms and radiologic
      findings mimicked those of acute intramural hematoma of the aorta. Upon emergency
      operation, he was proven to have a postinfarction LV rupture and underwent
      successful surgery. We herein report the case with a brief review of the
      literature.

PMID- 11519088
TI  - Occupational asthma due to formaldehyde.
AB  - Formaldehyde is a low molecular weight chemical and can elicit acute and chronic
      health related problems. Most of the inhaled formaldehyde is retained in the
      upper respiratory tract due to its extraordinary solubility. Therefore, cases of
      formaldehyde-induced occupational asthma are sporadic despite its widespread use
      in industrial processes. We herein report upon a case of occupational asthma due
      to formaldehyde, which was confirmed by workplace challenge including working
      environmental assessments, and by formaldehyde inhalation challenge using a
      specially designed closed-circuit apparatus. To investigate the possible
      involvement of an IgE-mediated mechanism, both in vitro and in vivo tests were
      done. IgE antibody specific for formaldehyde-human serum albumin conjugate (F
      HSA) was not detected by ELISA, and no specific cutaneous reactivity to F-HSA was
      noted by either skin prick or intradermal test. The patient was diagnosed with
      formaldehyde-induced occupational asthma not associated with an IgE mediated
      mechanism.

PMID- 11519090
TI  - CT and MR findings of primary cardiac lymphoma: report upon 2 cases and review.
AB  - Although primary cardiac lymphoma was a near fatal disease in the past, recent
      advances in imaging diagnosis and chemotherapy have dramatically improved
      survival. We describe the CT and MR findings of primary cardiac lymphoma in two
      immunocompetent subjects who recovered after chemotherapy. The primary cardiac
      lymphomas manifested as a poorly enhancing mass on CT, relatively hyperintense on
      a T2-weighted image and a heterogeneously enhanced mass on contrast-enhanced MR.
      The tumor also showed a predilection for right heart chambers and contiguous
      infiltration along adjacent structures.

PMID- 11519089
TI  - Choroidal tuberculoma with membranous glomerulonephritis.
AB  - We report treatment of a 24-year-old man with membranous glomerulonephritis (MGN)
      who developed a solitary choroidal tuberculoma in association with miliary
      tuberculosis during steroid therapy. In June 1995, the patient had developed
      nephrotic syndrome. He had refused renal biopsy at that time. So we treated him
      with corticosteroids having assumed a diagnosis of minimal change nephrotic
      syndrome. After initial corticosteroids and diuretics therapy for 5 months, his
      generalized edema resolved but proteinuria (3 positive) continued, suggesting the
      presence of other forms of glomerulonephritis. Renal biopsy performed in January
      1996. The patient was diagnosed as having MGN. The patient was closely observed
      over a period of 34 months and remained stable without steroid therapy. However
      at 34 months, generalized edema was again noted and steroid therapy at high
      dosage was initiated. After 5 months of steroid therapy, he developed miliary
      tuberculosis and a solitary choroidal mass. An antituberculosis chemotherapeutic
      regimen was started and after a further 5 months, all clinical symptoms and signs
      of the pulmonary lesion were resolved and a measurable shrinking of the choroidal
      mass was recorded.

PMID- 11519091
TI  - Helicobacter pylori infection in Korea.
AB  - Helicobacter pylori is a gram-negative bacterium that was first isolated in 1982.
      Since then, H. pylori infection in humans has been shown to be associated with
      gastritis, peptic ulcer disease, gastric carcinoma, and mucosa-associated
      lymphoid tissue (MALT) lymphoma as well. The epidemiology, transmission, and
      pathogenicity of H. pylori has been a subject of intensive study. Successful
      treatment improves the cure rate of peptic ulcerations and treatment with
      antimicrobials also decreases the recurrence rate of these diseases. Better
      regimens having less toxicity and a good eradication rate have also been
      developed. A better understanding of the pathophysiologic mechanisms relating to
      H. pylori induced mucosal damages would result in more options for the prevention
      of peptic ulcers and carcinogenesis. Korea has a relatively high incidence of H.
      pylori infection and gastric cancer. Growing interest has developed in view of
      its importance in being associated with various gastroduodenal diseases.
      Furthermore, along with a high incidence of H. pylori-related disease in Korea,
      because the interaction between H. pylori, host factors and environmental factors
      is important in disease pathogenesis, we need to have precise data on the
      characteristics of H. pylori-related diseases that occur in Korea. In the present
      report we review the epidemiology, transmission route, diagnosis, pathogenesis,
      treatment methods and relationship with gastroduodenal diseases with in special
      references to basic and clinical data that have been published.

PMID- 11519092
TI  - [Primary care of kidney diseases].

PMID- 11519093
TI  - [Long-term prognosis of kidney diseases and significance of primary care (based
      on the current status of chronic dialysis therapy in Japan)].

PMID- 11519094
TI  - [Significance and current status of urine examinations conducted at school].

PMID- 11519095
TI  - [Significance and the current status of urinalysis and serum creatinine
      determination for adults (with special reference to the health examination data
      at Ibaragi Prefecture].

PMID- 11519096
TI  - [Compromised kidney functions among the aged].

PMID- 11519097
TI  - [Cooperation between primary care physicians and nephrologists (the current
      status and the future of nephrologists, including a comparison between Japan and
      the United States)].

PMID- 11519098
TI  - [Need for the therapeutic guidelines (sequence in urinalysis) in examining cases
      with abnormal urinalysis results].

PMID- 11519099
TI  - [Management of patients who have been found to suffer from hematuria].

PMID- 11519100
TI  - [Management of patients who have been found to suffer from proteinuria].

PMID- 11519101
TI  - [Patients with edema].

PMID- 11519102
TI  - [Patients reporting abnormalities in urination].

PMID- 11519103
TI  - [Patients with rapidly deteriorating renal functions].

PMID- 11519104
TI  - [Patients who were found to have an electrolyte abnormality].

PMID- 11519105
TI  - [Kidney disorder developing in diabetic patients].

PMID- 11519106
TI  - [Renal disorders developing in hypertensive patients].

PMID- 11519107
TI  - [Kidney diseases associated with hyperuricemia].

PMID- 11519108
TI  - [Kidney diseases associated with hyperlipidemia].

PMID- 11519109
TI  - [Kidney diseases caused by collagen diseases].

PMID- 11519110
TI  - [Mechanism by which proteinuria exacerbates kidney diseases].

PMID- 11519111
TI  - [Molecular mechanism for the onset and progression of IgA nephropathy].

PMID- 11519112
TI  - [Primary care of kidney diseases: discussion].

PMID- 11519113
TI  - [Purpura due to vasculitis induced by interferon therapy for a patient with
      chronic hepatitis type C].

PMID- 11519114
TI  - [Aged watery diarrhea, hypokalemia, achlorhydria (WDHA) syndrome].

PMID- 11519115
TI  - [Pulmonary aspergillosis with a fungus ball typically observed by bronchoscopy].

PMID- 11519116
TI  - [Two cases of parrotfish poisoning with rhabdomyolysis].

PMID- 11519117
TI  - [Continuous ambulatory peritoneal dialysis (CAPD) patient with peritoneal
      sarcoidosis leading to lowering of dialysis efficiency].

PMID- 11519118
TI  - [Pulmonary Kaposi's sarcoma successfully diagnosed by transbronchial lung
      biopsy].

PMID- 11519119
TI  - [Treatment after heart transplantation and management of postoperative
      complications].

PMID- 11519120
TI  - [Genetic diagnosis of malignant lymphoma].

PMID- 11519121
TI  - [Prostate tumor and its diagnosis].
AB  - Prostate cancer and benign prostatic hyperplasia(BPH) are common diseases of in
      elderly men. Prostate cancer is a leading cause of morbidity and mortality in men
      in western countries. In Japan, especially, prostate cancer deserves our
      attention, because Japan has already become one of the most rapidly aging
      societies in the world. The morbidity and mortality rates of prostate cancer in
      Japan are now increasing steadily in recent years, although those rates are still
      very low compared with the rates in western countries. Fortunately, an excellent
      tumor marker, PSA, is available to detect early stage prostate cancer. In Gunma
      prefecture, we started mass screening for prostate cancer in the Ohta
      district(one city, three towns and one village) in 1981. In 2000, 36 of 70
      cities, towns, and villages conducted mass screening for prostate cancer. We
      obtained the important results from long-term follow-up of mass screening for
      prostate cancer in Gunma prefecture. That is, patients who were detected by mass
      screening were in an earlier stage and survived longer than patients who were
      found out in hospitals. Lastly, I present the report of the PSA Ad Hoc Committee
      of the Japanese Urological Association in 2000.

PMID- 11519122
TI  - [Evaluation of dysmorphic red cells in the urinary sediment].
AB  - The usefulness of the morphologic examination of urinary red cells was first
      described by Birch and Fairley, who reported that the dysmorphic red
      cells(morphologically variable) were the marker for glomerular bleeding and the
      isomorphic red cells(morphologically uniform) for non-glomerular bleeding. They
      also noted that healthy individuals had dysmorphic cells, indicating a glomerular
      source. The relation between red blood cell morphology and the origin of
      hematuria has been confirmed subsequently by numerous clinical studies. Although
      the reports varied on the ratio(10-100%) of dysmorphic cells, their findings have
      been supported by many investigators. In 1991 Kohler noted that acanthocytes(AC)
      were the most characteristic red cell type for glomerular bleeding and that
      acanthocyturia > or = 5% was a good predictive marker for glomerular bleeding.
      Moreover the red cell was easily recognized. On the other hand, in 1993 Fairley
      and Birch reported that in glomerulonephritis, erythrocytes varied markedly in
      size, shape, and hemoglobin content, and that the pattern of morphology indicates
      the source of bleeding, not the morphology of individual cells. Both observations
      were confirmed in our in vitro experiments. To clarify the causative mechanism of
      acanthocyturia, the normal washed erythrocytes were successively exposed to two
      kinds of solutions simulating conditions in the distal tubules(105 mOsm, pH 5.5,
      NaCl 37 mmol/l, KH2PO4 1.0 mmol/l, Urea 0.9 g/l) and the collecting tubules(a
      mixture of NaCl and KH2PO4 solutions with the osmolality between 299 and 1192
      mOsm). Various degrees of hemolytic process appeared in the first solution.
      However, AC appeared only in the second solutions with 9 mmol/l of KH2PO4 and 390
      mOsm or more osmolality or with 725 mOsm and 4.1 mmol/l or more of KH2PO4. This
      result supported the nephron passage theory in the formation of AC in glomerular
      diseases.

PMID- 11519123
TI  - [Living-related liver transplantation and clinical pathology].
AB  - More than 1,100 cases of living-related liver transplantation have already been
      performed in Japan. It achieved good survival rates, 83.6% in children and 74.5%
      in adults. These good results depend on not only development of
      immunosuppressants and improvement of surgical techniques but also on progress of
      clinical examination and postoperative management. Many kinds of clinical
      examination were frequently performed after liver transplantation. Liver
      transplantation cannot be performed without the cooperation of staffs who are
      involved in clinical examination.

PMID- 11519124
TI  - [Clinical significance of anti-liver-type arginase autoantibody in blood of
      recipients after partial liver transplantation].
AB  - Autoantibody against human liver-type arginase was detected in blood of patients
      treated with partial liver transplantation and consisted of all subclasses of
      IgG, i.e., IgG1, IgG2, IgG3 and IgG4, and IgM. We newly constructed an ELISA
      system for the antibodies by the aid of arginase protein immunopurified from
      extracts of human liver tissues. Addition of 2.0 mol/l urea in 0.1 mol/l citrate
      buffer(pH 4.5) was effective for elimination of immunoglobulins, such as IgG and
      IgM, and rheumatoid factors adsorped non-specifically to liver-type arginase
      autoantibody complexes on the plate. We found that, during a short period of
      about two months after operation, in successful cases, liver-type arginase
      increased, remarkably and repeatedly, in blood of recipients followed by
      elevation of IgM level within a week and also IgG2 level two or three weeks
      later. Thus the change in IgG2 level seemed to depend on those of the arginase
      and/or IgM. However, in unsuccessful cases, such fluctuation was not so clear as
      the successful cases. To be noteworthy was production of autoantibodies directed
      to liver-type arginase in blood of patients with liver injury although the
      arginase, as well as AST and ALT, is an enzyme which leaks out of liver tissue.
      Appearance of the autoantibodies in blood supports occurrence of liver injury, in
      part, in graft liver because the enzyme exists exclusively in the liver. Among
      immunoglobulins to liver-type arginase, IgG2 seemed to be the most helpful index
      to know rightly postoperative conditions of recipients of liver transplantation,
      and its measurement could be useful for long-term follow-up of the patients.

PMID- 11519125
TI  - [Roles of clinical laboratory monitoring in bone marrow and peripheral blood stem
      cell transplantation].
AB  - Hematopoietic stem cell transplantation(HSCT) increase the chances of cure of
      many hematological malignancy. The clinical laboratory plays a major role in
      support of HSCT. Both transplantation-specific laboratory test(tissue typing,
      assessment of graft viability/rejection, evaluation of minimal residual disease,
      and measurement of immunosuppressive drugs) and routine clinical laboratory
      tests(biochemical, hematological, serological, urinary, bacteriological, and
      physiological examinations) are significant. Hematopoietic stem cells(HSC) are
      usually assessed as CD34+ cells, while immature cells determined by automated
      hematology analyzers can simply evaluate HCS. These automated immature cell
      counts are earlier markers of engraftment following transplantation than the
      traditional indicators(neutrophils and platelets). After transplantation,
      infections, regimen-related toxicities, graft-versus host disease, veno-occlusive
      disease, and thrombotic microangiopathy are the serious complications, which are
      causes of expected mortality and morbidity in HSCT. Clinical laboratory
      monitoring may contribute early diagnosis and treatment of the complications,
      resulting in prevention of the adverse events.

PMID- 11519127
TI  - [Present and future of vaccines].
AB  - It is advised to understand present status of vaccines to start of review history
      of vaccine development. Any vaccine currently used has some problems to be
      improved. In addition to the efficacy or safety, cost of vaccine provide a
      problem. Drugs and Cosmetics Act describes regulations to ensure quality of
      vaccines. The Minimum Requirement of Biological Products concerns a soft ware of
      vaccines and GMP regulates hard ware of vaccine production. Some vaccines such as
      malaria, AIDS, hepatitis C vaccines are on the way of development in the world.
      New technology such as DNA vaccines or vaccine for application to mucous
      membranes are being applied. A new concept of vaccine is presented as a
      prophylactic tools for cancer, auto-immune diseases or allergic diseases which
      some key proteins are known as triggers.

PMID- 11519126
TI  - [Therapeutic drug monitoring of immunosuppresants].
AB  - The pharmacokinetics and pharmacodynamics of tacrolimus were evaluated in the
      pediatric recipients of living-related liver transplant. The mean clearance for
      tacrolimus was estimated with large interindividual variability and was shown to
      change as a function of days after operation. The therapeutic blood concentration
      of tacrolimus ranges were concerned from nearly 10 to 20 ng/ml. We have examined
      whether the expression levels of the intestinal absorptive barriers, MDR1 gene
      product P-glycoprotein and cytochrome P450 IIIA4(CYP3A4), correlate with the
      trough levels of orally administered tacrolimus in a recipient of small bowel
      transplant for 4 months. Both the MDR1 and CYP3A4 mRNA levels changed markedly
      through out this period. The tacrolimus concentration/dose ratio correlated well
      with the mRNA expression level of MDR1, but not CYP3A4. Intestinal P-glycoprotein
      rather than CYP3A4 is a good probe to predict the intraindividual variation in
      the tacrolimus pharmacokinetics.

PMID- 11519128
TI  - [DNA vaccine].
AB  - DNA vaccine involves the injection of plasmid DNA encoding an antigen under the
      control of an eukaryotic promoter, and results in cellular and humoral immune
      responses to the plasmid DNA-encoded antigen. The immune response induced by DNA
      vaccine usually has a T-helper-1(Th1) bias through a potent Th1-promoting
      adjuvant effect of immunostimulatory DNA sequences with CpG motifs present in
      plasmid DNA. It has been demonstrated that volunteers who were vaccinated with
      plasmid DNA encoding a malaria protein or a human immunodeficiency virus protein
      developed antigen-specific, human leukocyte antigen(HLA)-restricted, CD8+
      cytotoxic T lymphocytes(CTLs) The demonstration in humans of the induction of
      CD8+ CTLs by DNA vaccines, including CTLs, provides a foundation for further
      clinical application of this potentially revolutionary vaccine technology.

PMID- 11519129
TI  - [Laboratory investigation on M-protein and its clinical application. 1.
      Introduction].
AB  - Monoclonal protein is the immunoglobulin and its fragments which are originated
      from a monoclonal clone of immunoglobulin synthesizing cell. It is an actually
      tumour marker for B cell lymphoproliferative disorders. It is also observed in
      non-lymphoproliferative disorders such as solid tumor, infection, and
      immunodeficiencies. Monoclonal gammopathy of undetermined significance(MGUS) can
      be defined as a state of pre-malignancies, especially development of myeloma
      should be carefully followed. The paper outlines a routine-based laboratory
      approach on monoclonal protein in relevance with its classification, laboratory
      methods and the related diseases, thus giving general orientations for the paper
      followed.

PMID- 11519130
TI  - [The clinical significance of M proteins].
AB  - M protein refers to a monoclonal gammaglobulin that is produced by the monoclonal
      proliferation of plasma cells. More than 50% of M proteinemia is classified as
      MGUS, but lymphoproliferative disorders such as multiple myeloma and
      Waldenstrom's macroglobulinemia may also develop from MGUS. Therefore, in
      patients with MGUS it is very important to observe the clinical course. MGUS
      develops in many disorders including chronic infection, autoimmune disease,
      various type of neoplasm, neurological disease and skin disease. In general, no
      treatment is required for MGUS and smoldering type myeloma in which the clinical
      course and laboratory data are stable. However, in progressive myeloma or cases
      of plasmacytoma chemotherapy, radiation and/or surgery are indicated. Some
      factors are known to predict the prognosis of multiple myeloma, and poly(A)
      polymerase may be a useful indicator for predicting the prognosis of multiple
      myeloma.

PMID- 11519131
TI  - [Effects on M-protein on laboratory data].
AB  - We describe two patients with abnormal immunoglobulins: Case 1 was a non-diabetic
      patient with IgA-kappa type M-protein whose serum fructosamine(FRA) value was
      markedly elevated; and Case 2 was a patient with pseudo-leukocytosis induced by
      the interaction of etylenediaminetetraacetic acid(EDTA) and IgG-kappa type M
      protein. The M-protein in Case 1 was found to be conjugated to serum albumin by
      immunoelectrophoresis. By gel filtration, the FRA peak of the patient's serum was
      shown in the high molecule weight fraction. The glycation of IgA-kappa type M
      protein was clearly demonstrated by FRA staining after fractionation by serum
      protein electrophoresis. Although serum FRA values of other non-diabetic patients
      with IgA type M-protein were elevated, patients with IgG type M-protein and IgM
      type M-protein had low or normal serum FRA values. In Case 2, the white blood
      cell count of the patient's blood anti-coagulated with EDTA was 52,300/microliter
      as determined using an automated counter, but was within normal limits when
      counted manually by light microscopy using a hemacytometer. The white
      precipitates were formed by the interaction of the patient's serum with EDTA.
      Immunofixation electrophoresis revealed that the precipitates were IgG2-kappa
      type M-protein.

PMID- 11519132
TI  - [A case of IgG4-lambda type monoclonal immunoglobulin that interfered with
      determinations for albumin, direct bilirubin and iron in serum].
AB  - We report a human IgG4-lambda type M-protein that reacts with reagents of
      albumin, direct bilirubin and iron. Blood chemistry findings by an automated
      analyzer were: total protein 8.8 g/dl; albumin(ALB) 9.2 g/dl; direct bilirubin(D
      Bil) -6.2 mg/dl; and iron(Fe) 25 micrograms/dl. The white precipitates were
      formed by the interaction of the patient's serum with reagents of ALB, D-Bil, and
      Fe. Immunofixation electrophoresis revealed that these precipitates were the IgG4
      lambda type M-protein. Western blotting analysis showed that the IgG4 molecules
      were composed of two 55 kDa gamma 4 chains and two 24 kDa lambda chains.

PMID- 11519133
TI  - [A case of IgA2-lambda type M-protein that IgA concentration differs from the
      values of M-protein by serum protein electrophoresis].
AB  - We report an IgA-lambda type M-protein in which the IgA concentration differed
      from the values of M-protein by serum protein electrophoresis found in a 53-year
      old man with multiple myeloma. The M-protein value as determined by serum protein
      electrophoresis was 6,170 mg/dl. However, the serum IgA concentration was 3,052
      mg/dl by turbidimetric immunoassay. Immuno-fixation electrophoresis using IgA
      subclass antisera revealed that this M-protein was the IgA2-lambda type. Western
      blotting analysis showed that the IgA2 molecules were composed of two
      approximately 68 kDa alpha 2 chains and two 28 kDa lambda chains. In addition the
      free lambda chain band was detected at the position of 28 kDa without 2
      mercaptoethanol(2-ME) even though the patient IgA was purified. Since it is known
      that IgA2m(1) allotype easily release light chains from the IgA molecules in SDS
      PAGE without 2-ME, we speculated that in this patient the IgA was the IgA2m(1)
      allotype. After peripheral blood stem cell transplantation(PBSCT), immunofixation
      electrophoresis of the patient serum revealed not only the bands of IgA2-lambda
      type M-protein, but also three bands of IgG1-kappa type M-protein in the gamma
      region.

PMID- 11519134
TI  - [Heavy chain deposition disease: report of a case and review of the literature].
AB  - A 35-year old woman was admitted to our hospital because of systemic edema.
      Laboratory examination revealed that she had Bence Jones protein(lambda),
      hypocomplementemia, and proteinuria(0.5 g/day). Renal biopsy showed nodular
      glomerular lesions with IgG heavy chain and C3 deposition, but not other
      immunoglobulin and light chains. An extensive study about the character of
      circulating and deposited IgG demonstrated that the complexes of CH2-CH3 lacking
      CH1 domain was an important factor in the glomerular heavy chain deposition.

PMID- 11519135
TI  - [Recent progress in molecular diagnosis of deep-seated mycoses].
AB  - Diagnosing deep-seated mycoses continues to be a major challenge for the
      clinician. The non-culture-dependent laboratory assay with high sensitivity and
      specificity are needed for rapid diagnosis of deep-seated mycoses. Future
      clinical mycology laboratories will increasingly utilize DNA-based methods for
      the recognition of pathogenic fungi in patient specimens and for the
      identification of fungal isolates. Over the last ten years, increasing numbers of
      papers were published which document the molecular biological methods feasible to
      detect fungus-specific DNA sequence in clinical specimens. The polymerase chain
      reaction(PCR) and internal probes are central to these procedures. More recently,
      the non-isotopic in situ technique has been applied in the detection of
      pathogenic fungi. These methods have the potential to improve diagnostic accuracy
      and hasten the institution of specific antifungal therapy. This article will
      review some of the recent advances in molecular diagnosis of fungal infections.

PMID- 11519136
TI  - [Reference intervals of urinary biochemical analysis in Japanese men].
AB  - To determine the reference intervals of urinary albumin, immunoglobulin G,
      transferrin, alpha 1 microglobulin, and N-acetyl-beta-D-glucosaminidase, we
      measured those components and creatinine in urine from men with normal blood
      pressure(systolic < or = 139 mmHg and diastolic < or = 89 mmHg), HbA1c < or =
      5.8% and negative qualitative tests of urinary protein and hematuria. The
      subjects were 150 men in their thirties, 136 in their forties, and 135 in their
      fifties. Urines was collected in the morning after at least 12 hours fast and
      stored at -80 degrees C until assayed. The levels of creatinine decreased with
      age, whereas no change was observed in the levels of other urinary components.
      Consequently, the levels of those components expressed as g. creatinine increased
      with age. The reference intervals per g. creatinine were determined for each age
      bracket using the iterative truncation method after logarithmical transformation
      of the values.

PMID- 11519137
TI  - [Hepatitis C virus genotyping by restriction fragment length polymorphism of
      polymerase chain reaction products generated with a HCV detection kit].
AB  - Highly conserved sequence in the 5' untranslated region(UTR) of hepatitis C
      virus(HCV) genome have been targeted by most nucleic acid amplification-based
      detection assays, such as Amplicor HCV test, a commercially available assay kit.
      In this study, we classified HCV genotypes by direct sequencing determination for
      5' UTR of nested-PCR after Amplicor HCV test. Then, based on the results of
      sequence, RFLP analysis after digestion of the nested PCR fragments with Hae III
      or Sau 3AI to classify HCV genotype was evaluated. RFLP analysis distinguished
      the type 1, 2a and 2b. Only one of 29 samples was not classified by RFLP analysis
      due to the point mutation of Hae III recognition site. HCV genotypes commonly
      found in JAPAN were classified into three types, 1b, 2a, and 2b. Also, RFLP
      analysis requires fewer resources than serotype grouping test. Hence, the present
      method provides an adaptable and rapid HCV genotyping in clinical laboratory in
      JAPAN.

PMID- 11519139
TI  - [A history of famous hypotheses and the future development of studies on
      affective disorders].
AB  - The two famous hypotheses for the pathophysiology of affective disorders examined
      the role of deficiencies in catecholamine(Schildkraut, 1965) and
      indoleamine(Coppen, 1967). In the catecholamine hypothesis, Schildkraut proposed
      that some depressions were associated with an absolute or relative decrease in
      available norepinephrine at central adrenergic receptor sites. In the indoleamine
      hypothesis, there was evidence that the biochemical disturbances in three main
      areas; in amine metabolism, electrolyte distribution and hormonal function,
      played a role in affective disorders. This review attempts to find newer studies
      of affective disorders influenced by the two hypotheses. With the development of
      neurobiology and the availability of new tools over the last three decades,
      authors have generated newer theories for current studies. The functional roles
      of GABA, glutamate and dopamine have lead to the generation of newer hypotheses.
      The neurogenesis hypothesis provides evidence of a novel concept for the
      pathophysiology of affective disorders.

PMID- 11519140
TI  - [Epidemiological study of depression in Japan].
AB  - Recent epidemiological studies in Western countries have been carried out using
      either questionnaires or diagnostic structured interviews. Use of these
      instruments enhances the reliability and validity of epidemiological diagnoses
      and of transcultural comparisons. In Japan, psychiatric epidemiology is still in
      the 'neonatal' stage. A very limited number of studies have used a structured
      interview or operational diagnostic criteria. In these studies, the prevalence of
      Major Depression was surprisingly high, particularly in younger age groups. As in
      reports from Western countries, the prevalence was about twice as high among
      women as among men. In addition, some researchers have focused on depression in
      elderly or adolescent populations or in medical outpatients. However, such
      studies have all been of a small sample size. Studies with large samples are
      therefore required.

PMID- 11519141
TI  - [Intracellular signal transduction mediated via 5-HT and NA receptors].
AB  - The present brief review was discussed about the intracellular signal
      transduction mediated via 5-HT and NA receptors focussing on the mechanism of
      antidepressants. Recent studies demonstrated that long-term antidepressant
      treatments resulted in activation of cAMP pathway at several levels including
      CREB(cAMP response element-binding protein) and BDNF(brain-derived neurotrophic
      factor). These pathways are elevated via 5-HT and/or NA receptors which directly
      couple to the cAMP system(5-HT4,6,7 receptors or beta adrenoceptors), or via
      receptors that lead to activation of Ca(2+)-dependent protein kinase(5-HT2
      receptors or alpha 1 adrenoceptors). Such factors could be common targets for
      many different type of antidepressants. Elucidation of the signal transduction
      mediated via 5-HT and/or NA receptors, therefore, provide significant information
      understanding the pathophysiology of depression.

PMID- 11519143
TI  - [Current status of genetic study on affective disorder].
AB  - A series of studies have indicated the existence of genetic predisposition and
      the polygenic-multifactorial mode of transmission for bipolar disorder(BPD).
      Linkage studies have defined several BPD susceptibility loci. The findings to
      date suggested the candidate regions on 4p16, 12q23-24, 18p11, 18q22, 21q22, Xq24
      27 for BPD, although no genes has yet been definitively identified. There are
      also many reports on the analyses of candidate genes, using association studies.
      But none of gene polymorphisms have been established as firm disease alleles with
      sufficient replications. Novel statistical methods and development of new
      strategies are necessary to approach the goal of isolating susceptibility genes.

PMID- 11519142
TI  - [Function of monoamine neurotransmitter transporters].
AB  - Monoamine transporters include plasma membrane and vesicular monoamine
      transporters(VMAT). The former selectively and Na+/Cl(-)-dependently transport
      dopamine, noradrenaline and serotonin into the cytoplasma, and the latter non
      selectively carries monoamine into the vesicle. These transporters are composed
      of amino acid groups containing 12 folds more transmembrane components.
      Cytoplasmic transporters are a target site of certain drugs. Antiepileptic drugs
      such as SSRI and tricyclic antidepressants bind with serotonin transporter(SERT),
      noradrenaline transporter(NET) and/or dopamine transporters(DAT) to inhibit
      transport of monoamines into the cytoplasma, thereby increasing monoamine levels
      within the synaptic cleft. However, amphetamine, known to induce drug dependence,
      is transported by DAT and inhibit VMAT to induce reverse-transport of monoamines
      into the synaptic area, thereby producing psychiatric and behavioral alterations.
      Thus, monoamine transporters are target sites of drugs, and functional changes in
      the transporters may be involved in the pathogenesis of affective diseases,
      schizophrenia and/or personality disorders including neurogenerative diseases
      such as Parkinson's disease.

PMID- 11519144
TI  - [Role of life events on onset of major depression].
AB  - Many kinds of stressful life events have been regarded as important factors in
      the causation and management of depression, based on empirical and descriptive
      studies. The instrument for assessment of life events has been established. There
      is consistent evidence for dose-response relationship between stressful events
      and depression. The effect of life events close to onset is more important, but
      sometimes the expected response appears after a delay. The effect of life events
      varies by early adverse experience, cognition and genetics. The association
      between life events exposure and risk of major depression progressively declines,
      it is consistent with the kindling hypothesis.

PMID- 11519145
TI  - [The concept of mood disorder in ICD-10].
AB  - The classification of 'Manic-depressive illness(MDI)' has been changing in this
      several years greatly. MDI is recently named as a 'mood(affective) disorder'
      according to the ICD and DSM diagnostic system. Since 1990, with ICD-10(WHO), and
      1994, with DSM-IV(APA), practitioners have had at their disposal two(practically
      compatible) classifications of mental disorders containing operational criteria
      for diagnosis, and helpful in guiding clinical and therapeutic approach. In ICD
      10, mood disorder belongs to the F3 category, and there are seven subcategories
      which were divided in to subclasses. The two other subclasses of 'F06.3 organic
      mood disorder' 'F41.2 mixed anxiety and depressive disorders' were set up
      additionally.

PMID- 11519146
TI  - [Classification of mood disorders: from the viewpoint of clinical psychiatry].
AB  - Various classifications of depression have been developed up to this time. They
      are divided into three categories--etiological, phenomenological and
      multidimensional classification. The author discussed characteristics of three
      classifications from the viewpoint of clinical psychiatry. Etiological
      classifications include Kielholz's one and Pichot's one. They are useful to guide
      to clinical practice, but clinical features are not clearly described in them.
      Phenomenological classifications include ICD-10 and DSM-IV. They are practical to
      facilitate research and improve communication among clinicians and researchers
      all over the world. Although their reliability is on the increase, they leave
      something to be desired in regard to pursuit of etiology. The most famous
      multidimensional classification in Japan is Kasahara and Kimura's one. It
      introduces multiaxial system that includes premorbid character, precipitating
      factor, clinical features, response to treatment, and course. However, it is not
      fully grounded in empirical evidence.

PMID- 11519147
TI  - [Symptomatology and diagnosis of depression].
AB  - It is characterized by mainly depressive mood and psychomotor retardation.
      Another symptoms are retardation of thought, diurnal change, anxiety,
      irritability, delusion of belittlement, etc. There are often somatic symptoms as
      loss of appetite, sleep disturbance, loss of body weight, constipation, etc.
      Depressive symptoms are often seen in schizophrenia, brain injury, endocrinosis
      illness and other somatic illness. Diagnosis of depression is carefully carried
      out by detailed interviews and symptoms. Recently diagnosis of depression is
      determined mechanically by DSM-IV or ICD-10. Neuro-endocrine tests as DST or Dex
      CRH test, are useful strategies in examination of depression.

PMID- 11519148
TI  - [The guideline for the treatment of mood disorders in USA and Japan].
AB  - Recently, the number of available antidepressants has increased dramatically and
      psychopharmacological treatment is becoming complex. It is important to present
      some guideline for supporting clinical decision making. Three different kinds of
      guideline for the treatment of mood disorders, that is, the APA style guideline,
      the algorithm and the consensus guideline, have been developed in our country.
      The APA style guideline and the algorithm are basically evidence based and the
      consensus guideline is developed through the consensus panel format. These
      guidelines should be used as 'a starting point' for specifying decisions that
      will be modified occasionally.

PMID- 11519150
TI  - [Tricyclic antidepressant, tetracyclic antidepressant].

PMID- 11519149
TI  - [Treatment of major depressive disorder--method and selection of the treatment].
AB  - There are many ways of treatment for depression. Among them the most popular and
      effective treatment is pharmacotherapy. In the acute phase, pharmacotherapy with
      antidepressants, certain forms of psychotherapy, the combination of
      pharmacotherapy plus psychotherapy, and electroconvulsive treatment have clearly
      proven to be efficacious in most types of unipolar depressive disorders. The
      common augmenting agents probably are lithium, thyroid hormone, dopaminergic
      agents, and mood stabilizers. Certain treatments may be more effective in
      specific subtypes; for example, light therapy is useful for seasonal affective
      disorder. During the 16-24 weeks following remission, patients with
      antidepressant medications in the acute phase should be maintained on these
      agents to prevent relapse. For patient pharmacotherapy or psychotherapy has not
      been effective, the use of ECT may be useful. Following the continuation phase,
      maintenance-phase treatment should be considered for patients who have many
      depressive episodes to prevent recurrences of major depressive disorder.

PMID- 11519151
TI  - [Selective serotonin reuptake inhibitor(SSRI)].
AB  - Selective serotonin reuptake inhibitors(SSRIs) are safe antidepressants and now
      widely used for the treatment of depression. Although there are five
      SSRIs(citalopram, fluoxetine, fluvoxamine, paroxetine, sertraline) available in
      the world, only two(fluvoxamine and paroxetine) are approved in Japan. SSRIs are
      also used for the treatment of obsessive-compulsive disorders, panic disorders,
      eating disorders and so on. Major side effects of SSRIs are gastrointestinal
      symptoms(especially nausea), neurological symptoms (particularly headache and
      tremor) and psychiatric symptoms(especially anxiety). While therapeutic effects
      of SSRIs seem to be related to desensitization of somatodendritic serotonin 1A
      autoreceptors in the raphe nuclei, other neurotransmitters and intracellular
      mechanisms may be also involved.

PMID- 11519152
TI  - [Serotonin-noradrenaline reuptake inhibitors(SNRIs)].
AB  - Pharmacology, clinical efficacy and tolerability of serotonin noradrenaline
      reuptake inhibitors(SNRIs) are overviewed. They include milnacipran, venlafaxine,
      duloxetine, MCI-225 and nefazodone, however, only milnacipran is currently used
      in Japan. Pharmacology of SNRIs is characterized by inhibition of both serotonin
      and noradrenaline at the presynaptic membrane and by weak affinity with receptors
      at the postsynaptic membrane, which expects the same efficacy on major depressive
      disorder(MDD) as tricyclic antidepressant drugs(TCAs) with less adverse effects
      in clinical use. Currently available evidences show that SNRIs possess
      antidepressant effects on MDD at least similar potencies to TCAs with more
      potencies than selective serotonin reuptake inhibitors. SNRIs are well tolerated
      in general and safer than TCAs. SNRIs can be considered to be first-line
      antidepressant drugs.

PMID- 11519153
TI  - [Reversible inhibitor of MAO-A(RIMA)].
AB  - Monoamine oxidase(MAO) inhibitors had been used in the treatment of depression
      since 1950s, but there is no MAO inhibitor available clinically in Japan. Liver
      dysfunction and tyramine's effect are main problems with MAO inhibitors.
      Reversible inhibitors of MAO-A(RIMA), new and improved MAO inhibitors, were
      developed and are widely used in Europe. RIMA causes less tyramine's effect and
      less liver dysfunction than classical MAO inhibitors do. Moclobemide, a RIMA, is
      under development in Japan(Phase II). An introduction of RIMA in Japan will be
      useful for the treatment of refractory depression and other anxiety disorders. We
      discussed pharmacological properties, clinical efficacy and safety of RIMA.

PMID- 11519154
TI  - [Side effects and its countermeasures of antidepressant].
AB  - We reviewed the side effects of antidepressants. Tricyclic antidepressants(TCAs)
      are associated with a higher frequency of adverse events than those of SSRIs and
      SNRIs, particularly with respect to anticholinergic-like effects(dry mouth,
      constipation, and blurred vision), delirium, and cardiovascular adverse events.
      On the other hand, SSRIs have some special side effects that include nausea,
      sexual dysfunction, and extrapyramidal symptoms. With regard to milnacipran, a
      member of the SNRI family, dysuria occurs at a higher frequency than with TCAs or
      SSRIs. When side effects occur, clinicians give patients symptomatic treatment or
      substitute the drugs that cause the adverse effects with other antidepressants
      that have different pharmacological effects.

PMID- 11519155
TI  - [Pharmacokinetics and drug interactions of antidepressive agents].
AB  - Tricyclic antidepressive agents(TCAs) are conventional antidepressant. Cytochrome
      P450(CYP) 2D6 is involved in the hydroxylation of TCAs, while N-demethylation of
      TCAs is mediated by other such as CYP2C19, 3A4 and 1A2. The elimination of TCAs
      is impaired by CYP2D6 inhibitors such as quinidine. Newer antidepressants,
      selective serotonin uptake inhibitors(SSRIs), are also metabolized in the liver.
      Fluvoxamine, an SSRI, is a potent inhibitors for CYP1A2 and CYP2C19, moderate for
      CYP3A4 and weak for CYP 2D6. Paroxetine, another SSRI, causes substantial
      inhibition of CYP2D6 activity. Milnacipran, a serotonin and noradrenaline
      reuptake inhibitor, is mainly excreted unchanged in urine and some part as its
      glucronide conjugate. In contrast to many SSRIs, milnacipran is devoid of
      metabolic inhibition.

PMID- 11519156
TI  - [Delusional depression].
AB  - Delusional depression, comparing to non-delusional depression, is characterized
      by severe depressive symptoms, high risk of recurrence, long duration of
      depressive episode, and is refractory to the treatment with antidepressants
      alone, besides amoxapine, which has the antagonistic property to dopamine 2
      receptor like an antipsychotic. The combination therapy of an antidepressant with
      an antipsychotic is a highly effective strategy as well as the electroconvulsive
      therapy(ECT). ECT tends to reveal higher therapeutic effects rather than the
      combination therapy. As to the combination therapy, lithium augmentation is
      clearly effective to the bipolar type. Atypical antipsychotics(clozapine,
      risperidone, olanzapine) have thymoleptic properties. They have been to reported
      to have therapeutic effects by monotherapy or combination with mood
      stabilizer(lithium). Thus, atypical antipsychotics are expected to be a new
      effective strategy for delusional depression.

PMID- 11519157
TI  - [Depression in late life].
AB  - Depression in the elderly is one of the most important psychotic disorder as well
      as dementia. In this report, at first we described the relation between brain
      organic disorder and depression in late life. It is very interesting that
      depression in late life has often comorbid process with vascular dementia and
      dementia of the Alzheimer type. In biological treatments for depression in late
      life, pharmacotherapy and modified electroconvulsive therapy are useful. We must
      be aware of the adverse side effects from the use of antidepressant, then SSRIs
      are selected for clinical depression of late life, because the SSRIs produce
      fewer side effects. Psychotherapeutic medication, such as cognitive behavioral
      therapy and reminiscence or life, review is useful for depression in late life.

PMID- 11519158
TI  - [The epidemiology and pathogenesis of postpartum depression].
AB  - Mood disorders--maternity blues, depression and bipolar disorders with psychotic
      features--are common and increased in rate during the postpartum period as
      compared to the non-postpartum period. Several authors showed a frequent
      recurrence of postpartum depression in women with a history of postpartum
      depression. Bloch, et al: (2000) showed that 5 of 8 women(62.5%) with a history
      of postpartum depression and none of the 8 control women developed significant
      mood symptoms during the withdrawal from high serum levels of progesterone and
      estradiol. These findings indicate that a history of postpartum depression
      produces hypersensitivity or reverse tolerance to subsequent exposure to an acute
      decrease of gonadal steroids at least for a subgroup of women with a past
      postpartum depression.

PMID- 11519159
TI  - [Psychotherapy of depression].
AB  - Patients with depressive disorder are often guilty of their dysfunction and
      desperate of their future. In acute stage, it is most important to give patients
      the insight into their illness and to give them such reassurance that they will
      recover with treatment. Clinicians should advise the patients to take a rest. To
      encourage and motivate the patients to do work or other activities is often
      harmful. In the recovery stage, it is useful for the patients to reflect on their
      premorbid personality and behavioral traits that facilitate the development of
      depressive disorder, which may lead to their changing way of life and prevent
      recurrence of the illness.

PMID- 11519160
TI  - [Early internal treatment of mild depression].
AB  - In the early 1970s, a number of observers hypothesized that there had been an
      increase in mild depression in the United State. Interest in mild depression had
      increased in the world. One manifestation of that interest was the decision in
      previous official Nomenclatures of WHO and APA to create separate category for
      affective disorders in the DSM-III. Patients of mild depression complain mainly
      of physical symptom, for example, headache, lumbago, abdominal pain, dizziness,
      sleep disturbance, appetite loss. Early internal treatment of mild depression
      consists of three factors, rest, antidepressants and psychosocial supports. Up to
      date, the first choice of antidepressants in SSRI. SSRI has antidepressive effect
      and less side effect than TCA.

PMID- 11519161
TI  - [Parkinson's disease].
AB  - Depression is a most common psychiatric complication of Parkinson's patients.
      Approximately 30% of Parkinson's patients show depressive mood changes. Loss of
      interest, feelings of hopelessness, marked loss of energy and psychomotor
      retardation are common depressive symptoms with parkinsonism. Suicidal ideations
      and delusions are less frequent in Parkinson's patients with depression in
      compared to endogenous depression. Somatic symptoms, like fatigue, constipation,
      headache, insomnia, loss of appetite, dizzinees and sweating are usually seen in
      Parkinson's patient with depression. Serotonin reuptake inhibitors and selegiline
      are recommended for the treatment of depression in parkinsonian patients.

PMID- 11519162
TI  - [Vascular depression].
AB  - It has been reported that 20-65% of cerebral infarction patients suffers from
      depression. On the other hand, elderly-onset depression has more cerebro-vascular
      changes such as deep white matter lesion and periventricular hyperintensity on
      MRI than young-onset depression. These findings together leads new disease
      category 'vascular depression' (VD), meaning depression primarily caused by
      cerebral infarction. VD patients show less family history and symptomatic changes
      within a day than those with non-vascular depression. Though anti-depressants are
      effective on VD, they have higher incidence of side effect on VD than on non
      vascular depression. Benzodiazepines and cerebral circulation and metabolism
      enhancers are also used in VD therapy. The prognosis of VD is worse than that of
      non-VD or cerebral infarction without depression.

PMID- 11519163
TI  - [Rheumatic disease and depression].
AB  - We reviewed depressive symptoms in rheumatic disease. In systemic lupus
      erythematosus(SLE), depressive symptoms are frequently mentioned with the
      prevalence rate about 30% and usually respond to antidepressant. The duration of
      symptoms is within two months in most patients. Antibodies to ribosomal P protein
      appear to be a specific marker for SLE with depression. Single photon emission
      tomography but magnetic resonance imaging may also be useful for predicting the
      development of depressive symptoms. We also reported a patient of dermatomyositis
      with manic-depressive state who showed decreased cerebral blood flow in the left
      frontal and temporal regions during depressive state.

PMID- 11519164
TI  - [Depression in cancer patients].
AB  - Depression in cancer patients is common and occurs throughout the course of
      cancer illness. We review diagnosing, treatment and palliative care issues as
      well as epidemiology and etiology of major depression in cancer patients. The
      prevalence of major depression in cancer patients was reported to range from 6 to
      42%. It reflects various cancer related variables, such as pain and low
      performance status as well as risks for major depression. To avoid under
      diagnosing depression in cancer patient, it should include not only psychological
      symptoms, but also physical symptoms. The treatment includes patient education,
      counseling, behavioral techniques and antidepressant medications. In palliative
      care setting, life review interview would be effective for depression.

PMID- 11519165
TI  - [Brain imaging in depression].
AB  - Structural brain imaging studies in major depression have revealed decreased
      hippocampal volume, decreased frontal lobe volume, decreased basal ganglia volume
      and increased subcortical hyperintensity lesions(SCH). Decreased hippocampal
      volume is thought to be related to hypercortisolemia. SCH is related to poor
      treatment response and clinical symptoms, thus has some value in clinical
      decision making. Functional brain imaging studies suggested decreased blood flow
      and metabolism in the frontal lobes and basal ganglia by positron emission
      tomography and single photon emission tomography, decreased adenosine
      triphosphate measured by 31P-magnetic resonance spectroscopy(MRS) in the frontal
      lobes and basal ganglia, and increased choline containing compounds observed by
      proton MRS.

PMID- 11519166
TI  - [Panic disorder and antidepressants].
AB  - Anxiety disorders, specifically, panic disorder, are the most common mental
      health disorders. Unless the clinician has a high index of suspicion, panic
      disorder or social anxiety disorder may remain undetected. Although quality of
      life(QOL) issues have long been recognized in severe psychiatric disorders, they
      have only recently come to be considered for the anxiety disorders. While the
      older tricyclic antidepressants(TCAs) are efficacious in the treatment of theses
      anxiety disorders, recent studies with paroxetine and other selective serotonin
      reuptake inhibitors(SSRIs) have emphasized the role of serotonin in the aetiology
      of these conditions. Both the TCA and SSRI antidepressants are effective in
      treating a wide variety of anxiety disorders. SSRIs, due to their greater safety
      and tolerability, should be the preferred choices in treating anxiety disorders
      in those instances.

PMID- 11519167
TI  - [Low serum cholesterol and suicidal behavior].
AB  - An increasing number of studies have shown that low serum cholesterol levels are
      associated with a risk of suicidal, violent, and impulsive behaviors. This
      article reviewed the literature on this possible association. Several randomized
      controlled trials of lowering cholesterol interventions did not reduce total
      mortality in spite of reduced mortality due to coronary heart disease. This is
      partly attributable to an increased mortality rate of death due to suicide or
      accidents among individuals with lowered serum cholesterol. Cohort studies have
      shown that individuals with low serum cholesterol levels are more likely to
      present depressive symptoms and suicidal acts in later years than those with
      higher cholesterol levels. Many studies comparing suicidal and control subjects
      have found an association between low serum cholesterol and suicidal behavior.
      Although contradictive results are also reported, further studies are warranted
      to conclude the possible relationship between low or lowering serum cholesterol
      and suicidal behavior. Clinicians should be aware of potential effects of
      lowering cholesterol interventions on behavioral symptoms.

PMID- 11519168
TI  - [The neuropathogenesis of Borna disease virus infection].
AB  - Borna disease virus(BDV) is a noncytolytic, neurotropic RNA virus that causes a
      disease of the central nervous system(CNS) in several vertebrate species,
      including horses, sheep, cats and ostriches. Epidemiological studies using
      peripheral blood or brain samples revealed that BDV can infect humans and that it
      may be related with certain neuropsychiatric disorders. The unique genetic and
      biological properties of BDV indicate that BDV develops a persistent infection in
      the CNS. Furthermore, a line of recent evidences suggests that BDV infection
      causes direct effects on brain functions in the absence of immunopathology
      related brain damage. In this review, we discuss about recent data regarding
      neuropathogenesis of BDV infections in animals and humans.

PMID- 11519169
TI  - [Current availability of genetic information of drug metabolizing enzymes,
      particularly on cytochrome P450(CYP)].
AB  - Genetic polymorphisms of drug metabolizing enzymes often associated with clinical
      alteration among individuals. Current understanding of the molecular basis of the
      polymorphism of drug metabolizing enzymes is reviewed, particularly on cytochrome
      P450(CYP). Pharmacogenetic/pharmacogenomic studies are started for the estimation
      of pharmacokinetics of drugs, but now expanding for a tool of individual
      optimization of drug therapy for both drug efficacy and safety, and also for the
      development of new drugs. Genotyping is a powerful tool for these purposes, but
      not always simple because of the existence of more than 20 alleles for a single
      enzyme in some cases. Accumulated evidence, however, shows that occurrences of
      ethnic difference are rather common for allele distribution of drug metabolizing
      enzymes. These data indicate the necessity of the genetic analyses of Japanese
      population prior to the application of the genetic information for drug therapy.

PMID- 11519170
TI  - [Clinical experience of new stereotactic radiotherapy system named CyberKnife].
AB  - The CyberKnife is a small linear accelerator mounted on a robot. The CyberKinfe
      has the IPS(Image Processing System) that evaluates the patient position during
      the treatment. If there is any movement of the patient, the robot chases the
      tumor. Invasive flame to fix the patient skull is not needed. From April 1998
      through July 2000, we applied the CyberKnife treatment for 136 sites in 94
      patients. Sixty-seven of 136 sites were metastatic brain tumors. Progression-free
      rate of tumors treated with 24-27 Gy at 3 months after treatment was 89%. There
      was no severe adverse effects except epilation. The CyberKnife treatment was
      applied for tumors in the body in USA. It will be available in Japan in near
      future.

PMID- 11519171
TI  - [Evolution from unicellular to multicellular organisms].

PMID- 11519172
TI  - [Mechanisms of development in plants].

PMID- 11519173
TI  - [Evo-devo of multicellular animals: four evolutionary steps to vertebrates].

PMID- 11519174
TI  - [Functional evolution of T-box gene family on animal development].

PMID- 11519175
TI  - [Evolution of MADS-box genes and reproductive organs in land plants].

PMID- 11519177
TI  - [Structure determination of the calcium pump of sarcoplasmic reticulum].

PMID- 11519176
TI  - [Functional role and molecular mechanism of intercellular signaling via gap
      junction].

PMID- 11519178
TI  - [RNA interference (RNAi): gene suppression by dsRNA].

PMID- 11519179
TI  - [In search of gene evolution from sequences].

PMID- 11519180
TI  - [Longitudinal studies on the health effects of exposure to environmental
      cadmium].
AB  - Renal damage induced by cadmium (Cd) results in a proximal renal tubular
      dysfunction, characterized by low-molecular weight (LMW) proteinuria, renal
      glucosuria, generalized aminoaciduria and decreased renal tubular reabsorption of
      uric acid and phosphate. Since LMW proteinuria is thought to be one of the
      earliest adverse health effects caused by Cd, the prevention of the progress of
      LMW proteinuria is important to avoid further deteriorations in the health
      condition. Follow-up studies on residents in Cd-polluted areas and Cd-exposed
      workers have indicated that Cd-induced LMW proteinuria is generally irreversible
      and progressive even after the cessation or reduction of exposure. The intensity
      of exposure and the body burden of Cd before the reduction of exposure may
      influence the prognosis of Cd-induced LMW proteinuria. Several studies have
      reported a gradual decline in the glomerular filtration rate even after the
      reduction of Cd exposure. Cohort studies performed in Cd-polluted areas of Japan
      showed that renal tubular dysfunction and a decreased glomerular filtration rate
      were strongly associated with increased risk of mortality. However, the results
      also suggested that overall mortality rates in Cd-polluted areas were not
      necessarily increased, because of the low mortality among those with urinary beta
      2-microglobulin concentrations < 1,000 micrograms/g creatinine. At present,
      incidence data are too limited to draw a conclusion regarding the cancer risk
      among residents in Cd-polluted areas.

PMID- 11519181
TI  - [The role of psychosomatic medicine in public health (hygieiology): an approach
      for lifestyle-related disease].
AB  - In the twenty-first century it has been hypothesized that lifestyle-related
      disease will account for more than 70% of all disease; thus, in the twenty-first
      the prevention and treatment of lifestyle-related disease will be of primary
      importance. Lifestyle differs from individual to individual. In the past
      preventive medicine has targeted groups while clinical medicine has dealt with
      disease. However, in the twenty-first century it will be necessary to integrate
      the two approaches to meet the needs of the individuals. Measures following the
      primary prevention of lifestyle-related disease will be the vital and they can
      only be delivered by primary care medicine. As a model that covers the prevention
      and treatment of lifestyle-related diseases, based on the conventional biomedical
      model, a systematic medical model that attaches importance to the relativity of
      all factors and individuality will be necessary. The medical model for
      psychosomatic medicine is the Bio-psycho-socio-ethical (ecological) model, and
      psychosomatic medicine has specific methods for implementing this model. We have
      used this perspective to explain the role of psychosomatic medicine in public
      health (hygieiology).

PMID- 11519182
TI  - [Recent trends in mortality, years of life lost (YLLs), and disability-adjusted
      life years (DALYs) attributable to tobacco in Japan].
AB  - To assess recent trends in mortality and disease burden from tobacco in Japan,
      the present study estimated the number of deaths, years of life lost (YLLs) and
      disability-adjusted life years (DALYs) attributable to tobacco for the years 1985
      and 1995. Since smoking prevalence is a very poor measure of population exposure
      to tobacco, this study employed an alternative measure of the attributable
      fractions based on excess lung cancer mortality. It is suggested that there was a
      significant increase in both the absolute numbers and age-standardized rates of
      tobacco-attributed mortality and disease burden over the decade, in particular
      from lung cancer and chronic obstructive pulmonary disease. In 1995, tobacco
      already accounted for 12% of total mortality, 16% of total male mortality and 7%
      of total female mortality. The burden of disease attributable to tobacco amounted
      to 10% of the total YLLs and 7% of total DALYs, suggesting that tobacco is
      probably a single major risk factor of mortality and morbidity in Japan.

PMID- 11519183
TI  - [Mercury concentration of fish in Tokyo Bay and the surrounding sea area].
AB  - Total mercury in the muscles of three fish species was analyzed in fish caught in
      Tokyo Bay and the surrounding sea areas, Sagami Bay and Choshi. Tokyo Bay is a
      semi-closed sea area surrounded by Tokyo, Kanagawa and Chiba prefectures. Sagami
      Bay and Choshi are open to the Pacific Ocean. A total of 412 fish consisting of
      northern whiting (Sillago japonica), flatfish (Limanda yokohamae) and sardine
      (Sardinops melanosticta) were caught in these areas over a 6 months period from
      November 1998 to April 1999. Total mercury concentration ranged from 0.008-0.092
      microgram/g (wet wt.) in northern whiting, 0.006-0.065 microgram/g in flatfish
      and 0.001-0.045 microgram/g in sardine. All concentrations were below the
      restriction limit of fish mercury in Japan, 0.4 microgram/g of total mercury
      concentration. A significant correlation was found between mercury concentrations
      and body length or body weight in northern whiting and flatfish, irrespective of
      the sea area. A correlation was also found between mercury concentration in fish
      and their feeding habits: among the 3 species caught in the same area, crustacean
      feeding northern whiting had the highest, polychaete feeding flatfish moderate,
      and plankton feeding sardine had the lowest mercury concentration. In a
      comparison of mercury concentration in the same species caught in different sea
      areas, a higher concentration was noted in fish caught in the semi-closed sea
      area of Tokyo Bay, than in fish caught in the open sea areas of Sagami Bay and
      Choshi. This difference was most marked in fish caught at the bottom of Tokyo Bay
      and we considered that the mercury concentration of seawater and sediment in
      these areas was the cause of mercury accumulation in fish. These findings suggest
      that improved water quality control and environmental monitoring is necessary in
      semi-closed sea areas such as Tokyo Bay.

PMID- 11519184
TI  - [Relationship between changes in skin lipids by ultraviolet exposure and the cell
      toxicity].
AB  - The oxidative decomposition of skin lipids by UV exposure and its cell toxicity
      were studied in vivo and in vitro, using guinea pigs, to investigate the role of
      oxidative damage in cell membranes and mitochondria in nuclear genome DNA damage
      resulting in skin cell death by ultraviolet (UV) exposure. Two new methods were
      developed for this research: selective methylation by trimethylsilyldiazomethane
      (TMSCHN2) of free fatty acids in crude skin lipids for gas chromatography-mass
      spectrometry (GC-MS) analysis, and the improvement of the thiobarbituric acid
      (TBA) reaction for lipid peroxide analysis, which was obtained by adding 0.01%
      BHT and 1 mM EDTA, an antioxidant additive, into the reaction system described by
      Ohkawa. The following findings were noted: 1. Using an optical microscope, the
      infiltration of inflammatory cells such as neutrophils, lymphocytes and monocytes
      was noted after skin tissue was exposed to UV. 2. The increase of lipid peroxide
      in exposed areas was small. In the epidermis the increase was about 2 times
      higher than the non-exposed areas. 3. The fragments of lipid were generated in
      accordance with the increase of free fatty acids (C16:0, C18:1,:2, C18:0) in the
      surface of the exposed skin by GC-MS precise assay, and the level of 7
      dehydrocholesterol was decreased. 4. The skin homogenate received peroxidation by
      ultraviolet more easily than living skin, and its peroxidation was inhibited with
      fat-soluble antioxidative agents such as flavonoids, BHT, BHA, and vitamin E and
      the metal chelating agent such as Fenton reaction inhibitor as expected; however,
      it was promoted by water soluble antioxidative agents such as glutathione and
      vitamin C, which are useful to the human body. 5. Steroids and nonsteroidal anti
      inflammatory drugs (NSAIDs) such as indomethacin and aspirin, had no inhibitory
      effect on lipid peroxidation by ultraviolet as properties of chemicals.

PMID- 11519185
TI  - [Association between life events, subjective health status and health practices
      in a rural population].
AB  - A survey has been conducted on subjective health status, experience of life
      events in recent 1 year, and health practices in the rural of Kagawa prefecture.
      The survey was performed from March 1995 to May 1995 with 4,013 participants,
      aged 40 to less than 80. The proportion of respondents who recognized their
      physical conditions as good decreased with age. However, the proportion of
      respondents who recognized their life satisfaction as good increased with age.
      'Health-related' life events were the most common experienced life events for
      both male and female. The proportion of respondents who had life events of type
      'family', 'financial', 'at workplace or job', 'in the community', and 'others'
      decreased with age. Men had higher proportion of 'at workplace or job' life
      events. The higher proportion of respondents who experienced life events
      recognized their subjective health status poor. For male, it observed that poor
      physical health status had significant association with experience of type 'in
      the community' and 'environmental' life events. Poor mental health status
      significantly associated with experience of type 'at workplace and job' life
      events for male, and with 'health-related' and 'family' life events for female.
      Poor life satisfaction significantly associated with 'at workplace or job' and
      'in the community' life events for male, and with 'health related' and 'family'
      life events. Higher proportion of the respondents who experienced life events and
      recognized their subjective health status poor had low health practice scores.
      Logistic regression analysis showed that experience of life events and poor
      subjective health status had significant association with the poor health
      practices, especially with 'body weight changed' for both male and female.

PMID- 11519186
TI  - [Study of remanent magnetization of the human body: lung and liver tissues].
AB  - In this study, we used lung and liver tissue specimens distracted from tissue to
      investigate remanant magnetization, and found that specimens with a volume of 6
      mm3 had an intensity of 10(-10) Am2, which was significantly stronger than the
      noise level of the superconducting magnetometer. This finding indicates that both
      lung and liver tissues contain magnetic materials. We speculated that biological
      magnetite is the magnetic material in these tissues. In addition, we found that
      lung tissue specimens with strong magnetization had correspondingly strong
      magnetized findings in the liver tissue specimens. In a comparison of
      magnetization in lung cancer tissue specimens and normal lung tissue, no
      significant relationship was noted, but two of the lung cancer tissue specimens
      showed strong magnetization. The number of lung cancer specimens studies was
      insufficient to investigate the relation between the magnetization (accumulation
      of magnetic materials) and lung cancer, and further studies are necessary. The
      magnetic properties of two lung cancer tissue specimens showing strong
      magnetization were further investigated, and an alternating field demagnetization
      experiment showed that their magnetization was composed of a unit stable vector,
      which indicates that the lung tissue may have been magnetized after the
      accumulation of magnetic materials. The Wohlfarth ratio (Moskowitz et al., 1989)
      of them was less than 0.5, which suggests that magnetic materials are distributed
      in clusters in lung tissue.

PMID- 11519187
TI  - [Ingestion and excretion of aluminum in foods and pharmaceuticals].
AB  - We measured the aluminum contents in foods and pharmaceuticals, and the aluminum
      concentrations in urine by atomic absorption spectrophotometry with polarized
      Zeeman background correction to obtain the daily intake and excretion of
      aluminum. The daily urinary excretions of aluminum in healthy females were
      obtained after consuming sea algae, hizikia fusiforme, which has a high aluminum
      contents. Daily aluminum excretion did not increase after taking hizikia
      fusiforme. On the other hand, high aluminum excretions were observed after taking
      an analgesic/antipyretic with a high aluminum contents, compared with the usual
      daily aluminum excretion (p < 0.001), and compared with after taking an
      analgesic/antipyretic with no aluminum (p < 0.0001). We found that the daily
      urinary excretion of aluminum was not related to the total consumption of
      aluminum, but depended on the binding state of aluminum consumed.

PMID- 11519188
TI  - [Relationships between walking hours, sleeping hours, meaningfulness of life
      (ikigai) and mortality in the elderly: prospective cohort study].
AB  - The purpose of this study was to determine lifestyle factors in the elderly that
      affected longevity, using a population-based prospective study. The participants
      were 440 men and 625 women aged 60 to 74 living in a rural Japanese community.
      The baseline data such as age, sex, present illness, walking hours per day,
      sleeping hours per day, alcohol consumption, a history of smoking, and "ikigai"
      (meaningfulness of life) were collected in July 1990. During 90 months of follow
      up from July 1990 to December 31 1997, there were 123 deaths. By Cox's
      multivariate hazard model adjusted age, sex, and medical histories, walking > or
      = 1 hour/day (HR = 0.63, 95% CI 0.44-0.91) and an "ikigai" (HR = 0.66, 95% CI
      0.44-0.99) lowered the risk for all-cause mortality independently. In regard to
      hours of sleep, the cumulative survival curve showed that 7 hours/day was the
      border and sleeping > or = 7 hours/day lowered the risk (HR = 0.49 95% CI 0.33
      0.74). Based on the findings in this study, walking > or = 1 hour/day, sleeping >
      or = 7 hours/day, and "ikigai" are important factors for longevity in the
      elderly.

PMID- 11519189
TI  - Error reporting and electronic medical records.

PMID- 11519190
TI  - The phlebotomist's role in the collection phase of a blood culture.

PMID- 11519191
TI  - E-learning for continuing education: exploring a new frontier.

PMID- 11519192
TI  - Using Web pages to improve laboratory services.

PMID- 11519193
TI  - [Current aspects of diagnosis and therapy of iron deficiency anemia in
      pregnancy].
AB  - Anaemia is one of the most common risk factors in the area of obstetrics and
      perinatal medicine. During pregnancy and in the puerperium it is associated with
      an increased incidence of both maternal and fetal morbidity and mortality, the
      extent of which is dependent upon the severity of anaemia and the resulting
      complications. In order to correctly diagnose the type and degree of anaemia, a
      prerequisite for selection of the proper therapy, one must first of all correctly
      differentiate between the relative, i.e., the physiological anaemia of pregnancy
      due to the normal plasma volume increase during pregnancy, and "real anaemias"
      with various different pathophysiological causes. When defining the Hb cutoff
      value for anaemia in pregnancy, the extent of the plasma volume changes with
      respect to the gestational age must be taken into consideration. It has been
      found that haemoglobin values < 11.0 g/dl in the first and third trimesters, and
      < 10.5 g/dl in the second trimester may point to an anaemic situation which
      should be further clarified. The first important steps for diagnosing anaemia in
      a pregnant patient include a thorough check of her medical history and a medical
      examination. This procedure often lays the basis for a correct diagnosis. The
      current gold standard to detect iron deficiency remains the serum ferritin value.
      To be reliable, this requires the ruling out of an infection (chronic or acute)
      as a cause of the anaemia. We recommend a complete laboratory test for the exact
      haematological status as well as the assessment of specific chemical laboratory
      parameters. These should include a palette of additional, promising new
      parameters such as hypochromic red cells and transferrin receptors which allow
      more accurate detection of iron deficiency and differential diagnosis of iron
      deficiency anaemia. After correct diagnosis, major emphasis should be put on safe
      and effective treatment of anaemia which again depends on severity of anaemia,
      time for restoration and patients characteristics. Today effective alternatives
      to oral iron only or blood transfusion such as parenteral iron sucrose complex
      and in selected cases also recombinant erythropoietin have been investigated and
      show promising results concerning effective treatment of anaemia during pregnancy
      and postpartum.

PMID- 11519194
TI  - [Is joint stability only a matter of ligaments?].

PMID- 11519195
TI  - [Lung infiltrations in Hodgkin lymphoma].
AB  - We report the case of a young patient presenting with cervical lymphadenopathy
      and interstitial pulmonary infiltrates due to Hodgkin's Disease. Although lung
      involvement regressed under chemotherapy, we observed new alveolar infiltrates
      during treatment. Steroid administration after exclusion of an infectious cause
      was followed by rapid clinical and radiological improvement, indicating the
      probable presence of pulmonary bleomycine toxicity.

PMID- 11519197
TI  - ["Marketing potential of the medical practice": theoretically interesting,
      practically useless prescriptions!].

PMID- 11519196
TI  - [Fever and microhematuria. cANCA-glomerulonephritis with arthralgia, myositis and
      possible vasculitic involvement of the aortic valve].

PMID- 11519198
TI  - [Glucocorticosteroid therapy in optic neuritis and multiple sclerosis. Evidence
      from clinical studies and practical recommendations].
AB  - High-dose intravenous glucocorticosteroids (GS) are the treatment of choice for
      acute relapses in patients with multiple sclerosis. We review the evidence from
      published trials on GS treatment in MS. Several controlled clinical trials have
      proven the efficacy of high-dose GS in accelerating the recovery from acute
      attacks. With serial MRI recordings, a reduction in the number of enhancing
      lesions has been observed after high-dose GS treatment. Definitive long-term
      effects of GS on disease evolution could not been demonstrated. There is now
      evidence that ultra-high doses of GS might be superior in comparison to standard
      pulse treatment regarding relapse rate and disease progression. In experimental
      autoimmune encephalomyelitis (EAE), an animal model for some features of MS,
      doses of up to 50 mg/kg methylprednisolone markedly augmented T cell apoptosis in
      situ, leading to a faster clearance of inflammatory infiltrates. Apoptosis in
      peripheral blood leukocytes could also be detected after i.v. GS treatment in MS
      patients. In a recent MRI study, ultra-high doses of GS were significantly more
      effective in reducing contrast-enhancing lesions and in maintaining blood-brain
      barrier integrity after a clinical relapse. Further clinical trials are necessary
      to study the long-term effects of ultra-high doses of GS on disease progression
      and disability.

PMID- 11519199
TI  - [Thrombolysis in cerebral ischemia. An overview].
AB  - Thrombolytic therapy for acute ischemic stroke within the 3-h time window has
      been approved. In the US, where FDA approval has existed for about 4 years, less
      than 2% of stroke patients presently receive thrombolytic therapy. This review
      illustrates all completed trials of intravenous and intra-arterial thrombolytic
      therapy for carotid artery and vertebrobasilar artery stroke and includes
      recommendations for therapy, diagnostic procedures and their effect on patient
      selection, meta-analyses, phase IV trials, and cost efficacy analyses.

PMID- 11519200
TI  - [Harmonic imaging. A new method of ultrasound imaging of brain perfusion].
AB  - In this review, methodological aspects of cerebral perfusion imaging with
      ultrasound contrast agents are described. The various experimental concepts
      contributing to an understanding of the phenomena are summarised and the
      resulting investigation techniques on patients are illustrated. By means of
      harmonic imaging, human cerebral perfusion can be depicted as a two-dimensional
      scan. The two major principles of contrast measurement are analysis of the bolus
      kinetics and analysis of the refill kinetics. Using the bolus method,
      hypoperfused areas in stroke patients can be visualised and parameter images of
      wash-in and wash-out curves can be generated off-line. The recently developed
      theory on the refill kinetics of UCA enables us to calculate parameters for
      describing the cerebral microcirculation, as they are less affected by the depth
      dependence of the contrast effect. These parameters can also be visualised as
      images. The ultrasound methods described in this article represent new minimally
      invasive bedside techniques for analysing brain perfusion. Although their
      development is still in an early stage, the potential of these ultrasound
      technologies to compete with perfusion CT, perfusion MRI, and SPECT in the
      diagnostic arsenal of brain imaging techniques is becoming evident.

PMID- 11519201
TI  - [Cardiac arrhythmias in Guillain-Barre syndrome. An overview of the diagnosis of
      a rare but potentially life-threatening complication].
AB  - Autonomic neuropathy is an important complication of Guillain-Barre syndrome
      (GBS). In particular, over-reactivity of vagal function may lead to serious
      cardiac disturbances ranging from bradycardia to asystole. Early recognition of
      these events is essential for appropriate intervention such as the insertion of a
      cardiac pacemaker. Recent studies indicate that serious bradyarrhythmias could be
      observed in severely and even less severely affected patients who were still able
      to walk more than 5 meters. Conventional measures such as the presence of
      tachycardia, heart rate and blood pressure fluctuations, or short-term heart rate
      variability and standardized autonomic function tests were not useful in
      predicting serious bradyarrhythmias. However, abnormal sensitivity to eyeball
      pressure testing correctly identified two of three patients who needed cardiac
      pacing or cardiopulmonary resuscitation due to heart arrest; eight of ten
      patients without bradyarrhythmic events showed normal responses. New methods such
      as the 24-hour heart rate power spectrum may yield sensitive and specific markers
      for assessing the risk of impending and potentially life-threatening arrhythmias
      in patients with GBS.

PMID- 11519202
TI  - [Myotonic dystrophy (DM/Curschmann-Steinert disease) and proximal myotonic
      myopathy (PROMM/Ricker syndrome). Myotonic muscle diseases with multisystemic
      manifestations].
AB  - Myotonic disorders are characterised by slowed muscle relaxation and myotonic
      discharges in the electromyogram. "Pure" myotonic disorders affect only muscle
      and can be separated into ion channel disorders affecting either the chloride
      channel (myotonia congenita Thomsen or myotonia congenita Becker) or those
      affecting the sodium channel (paramyotonia, hyperkalemic periodic paralysis, and
      myotonia fluctuans). The genetic defects in these disorders are point mutations
      or deletions within the respective channel genes. A second group of myotonias
      consists of multisystem disorders with muscle weakness and atrophy plus
      extramuscular symptoms and signs including cardiac arrhythmias, cataracts,
      hypogonadism, and pain. Classic myotonic dystrophy (Steinert's disease or DM 1),
      and proximal myotonic myopathy (PROMM or Ricker's syndrome) are the major
      syndromes. PROMM is characterised by predominantly proximal muscle weakness and
      myalgias. Similarly to DM 1, anticipation also occurs in PROMM, but the disease
      course is usually milder. Steinert's disease belongs to the group of
      trinucleotide repeat-associated disorders. The DM 1 mutation is an unstable CTG
      trinucleotide repeat expansion on chromosome 19q13.3 which is diagnostic for the
      disease. A number of families with PROMM have been linked to a gene locus on
      chromosome 3q, but the mutation is still unknown. Therefore, direct molecular
      genetic testing for PROMM is not yet possible.

PMID- 11519203
TI  - [Does cw Doppler ultrasound still have a value for cerebrovascular diagnosis
      today?].
AB  - The aim of this study was to assess the current value of extracranial continuous
      wave (cw) Doppler sonography in routine use as compared to color-coded duplex
      sonography. For this purpose, 500 carotid and 500 vertebral arteries were
      examined by a user experienced in both methods. The error rate of Doppler
      sonography was determined only when the methods allowed a clear decision to be
      made about the status of the vessel (normal findings including common variants,
      stenosis, and occlusion). In 85.4% of the carotid arteries and 88% of the
      vertebral arteries, the Doppler findings fulfilled the diagnostic differentiation
      unequivocally. For these cases, false findings were obtained in 1.9% of the
      carotid arteries and 0.2% of the vertebral arteries. Accordingly, a clear Doppler
      sonographic finding, normal or pathologic, is still of large diagnostic value.
      However, ambiguous or uncertain findings requiring further diagnostic workup are
      not uncommon. Thus, the sole use of cw Doppler sonography is no longer sufficient
      in a stroke center but still retains its utility in the practitioner's office.

PMID- 11519204
TI  - [Taste disorder caused by carotid artery dissection].
AB  - There exist only a few reports on loss of taste sensation caused by dissection of
      the internal carotid artery. We describe a patient with carotid dissection and
      ipsilateral ageusia in the anterior two thirds of the tongue, presumably from a
      lesion of the chorda tympani. Ageusia in carotid dissection is explained by the
      close anatomic relation of the internal carotid artery and the chorda tympani in
      the short petrous bone. However, since extension of the space-occupying,
      dissecting intramural hematoma into the carotid channel as in our patient occurs
      infrequently--a probable precondition for the chorda tympani lesion--loss of
      taste is accordingly very rare. Reduced perfusion of the vasa nervorum can be
      excluded as another cause, because the chorda tympani is supplied only from
      branches of the external carotid artery.

PMID- 11519205
TI  - [Bithalamic infarcts as the etiology of acute stupor. Early diagnosis with
      diffusion-weighted MRI].
AB  - Fast diagnostic evaluation of somnolent or unconscious patients is a demanding
      task for neurologists. Apart from postictal, metabolic, and toxic causes,
      vascular syndromes must be rapidly identified in order to initiate a specific
      fibrinolytic therapy. Given its high mortality if not treated in time, this
      dictum holds especially true for basilar artery occlusion. However, certain
      ischemic lesions in the vascular territory of the basilar artery without
      occlusion of the basilar artery itself can also result in somnolence, sopor, or
      even unconsciousness. Here we report early imaging signs of bithalamic
      infarctions as the cause of acute sopor using diffusion-weighted (DW)-MRI, which
      reliably identifies acute bithalamic infarctions as a possible cause of acute
      consciousness disturbance, even with noncooperative patients.

PMID- 11519206
TI  - [Familial myoclonus-renal failure syndrome].
AB  - In 1986 Andermann et al. described a syndrome presenting with renal failure,
      myoclonus, cerebellar symptoms, and epilepsy. They presumed a hereditary cause.
      We describe the first appearance of this syndrome in Europe, affecting three
      family members with comparable symptoms. Two of these patients were treated by
      us, and the third, already decreased, is described according to the available
      reports. The first clinical symptoms were manifested between the ages of 14 and
      20. A female patient suffered from compensated kidney insufficiency and her two
      brothers aged 18 and 26 required dialysis. Biopsy of kidney tissue revealed
      nonspecific nephritis. All cases showed a cerebellar syndrome and action
      myoclonus. Two of them were diagnosed with epilepsy and grand mal seizures, and
      all suffered from demyelinizing or mixed polyneuropathy. Anamnesis of the family
      seems to indicate autosomal recessive inheritance.

PMID- 11519207
TI  - [Parry-Romberg syndrome and Rasmussen syndrome: only an incidental similarity?].
AB  - The Parry-Romberg syndrome is a rare and poorly understood disease characterized
      by slowly progressive, localized atrophy of the skin, subcutaneous tissue,
      muscles, and bones. The atrophy is typically localized in the face and begins in
      youth. In some patients, imaging can show the lesions and atrophy of the
      ipsilateral hemisphere of the brain. We report on a patient in whom the disease
      has lasted 36 years and discuss the possibility that the Parry-Romberg syndrome
      is related to known autoimmune disorders of the soft tissue (e.g., linear
      scleroderma) and Rasmussen's syndrome. There are some remarkable clinical
      similarities between these two syndromes, including age of onset, unilateral
      manifestation, and occurrence of focal seizures. It is most probable that both
      diseases have an autoimmunological background.

PMID- 11519208
TI  - [Brain stem and cerebellar atrophy in neurosyphilis].
AB  - A 54-year-old man suffered from serologically proven neurosyphilis with
      tetraspastic syndrome and bladder dysfunction. He showed a pronounced psychopathy
      with cognitive decline and attention/concentration deficits. MRI showed slowly
      progressive cerebellar and brainstem atrophy, which has rarely been described
      over the past decades. During times of higher incidence and prevalence of
      neurosyphilis, infratentorial atrophy had been described occasionally, but today
      this clinical manifestation has been all but forgotten.

PMID- 11519209
TI  - [Proximal weakness and exercise-induced pain as initial symptom of
      oculopharyngeal muscular dystrophy].
AB  - A 54-year-old female patient presented with exercise-induced proximal muscle pain
      and weakness of the lower limbs. One year after the onset of these symptoms she
      developed bilateral ptosis and dysphagia. Molecular genetic analysis of the
      poly(A) binding protein 2 gene (PABP2) confirmed the presumptive diagnosis of
      oculopharyngeal muscular dystrophy (OPMD). Exercise-induced proximal muscle pain
      and weakness are rarely initial symptoms of OPMD. We discuss therapeutic options
      and present an overview of the relevant literature.

PMID- 11519211
TI  - Tenth circuit affirms LaHue/Anderson conviction in Kansas City Medicare anti
      kickback case.

PMID- 11519210
TI  - If you don't know where you're going, anywhere you end up is OK.

PMID- 11519212
TI  - The truth about underage drinking.

PMID- 11519213
TI  - Representative recent publications that document nutrient inadequacies in the
      elderly.

PMID- 11519214
TI  - ECG of the month. Sinister implications? Atrial flutter.

PMID- 11519215
TI  - Carcinomas of unknown primary in the head and neck.
AB  - In approximately 3% to 5.5% of patients presenting with squamous cell carcinoma
      metastasis to the cervical lymph nodes, the primary source remains elusive
      despite extensive evaluation and biopsy. The presenting symptom of a unilateral
      neck mass is initially evaluated with a complete history and physical. This is
      followed by flexible endoscopy, fine needle aspiration, laboratory and imaging
      studies and directed biopsies of the upper aerodigestive tract. While the initial
      attempt fails to locate the primary site, it will eventually become manifest in
      20% to 40% of patients. Early identification decreases overall morbidity and
      mortality. This article summarizes contemporary diagnostic approaches, current
      imaging techniques, the role of tonsillectomy, and the management and outcomes of
      carcinoma of unknown primary.

PMID- 11519216
TI  - Radiology case of the month. Primary tumor of bone. Conventional osteosarcoma.

PMID- 11519217
TI  - A night in 1888: the journal of a surgeon on call.

PMID- 11519218
TI  - Pheochromocytoma during pregnancy: a case report.

PMID- 11519219
TI  - Combined intralesional interferon alpha 2B and oral vitamin E in the treatment of
      Peyronie's disease.
AB  - It has been recently reported that intralesional therapy with alpha interferon 2B
      resulted in significant improvement of both objective and subjective complaints
      (penile curvature, pain, plaque size, sexual function) associated with Peyronie's
      disease. Vitamin E, with its antioxidant properties, may play a role in reducing
      the inflammatory response. This study was designed to determine the safety and
      effectiveness of a high dose of alpha INF-2B injected weekly into the Peyronie's
      plaque combined with oral Vitamin E therapy. Twenty-nine patients with Peyronie's
      disease were evaluated with penile duplex Doppler for degree of penile curvature,
      deformity, and plaque size both prior to and after treatment. Each patient then
      received 4.0 x 10(6) units of alpha INF-2B in 10 cc of normal saline after
      appropriate local anesthesia. Injections were given once per week directly into
      the Peyronie's plaque for a period of 10 weeks. Patients also received 400 units
      of Vitamin E by mouth twice a day. Subjective data was obtained via a
      questionnaire prior to and at the conclusion of the study. Preliminary results
      demonstrated improvement of penile curvature in 39% of patients, with one patient
      experiencing complete resolution. Significant decreases in plaque sizes were
      noted in 11 of these patients, with softening of the plaques noted in all
      patients completing the study. Seven patients dropped out of the study prior to
      completing the 10 weeks: three with severe disease proceeded to surgery, two were
      lost to follow-up, one had exascerbation of his arthritis symptoms, and one quit
      secondary to flu-like symptoms. Subjective data from questionnaires revealed
      improvement in sexual function in those men with decreased curvature and plaque
      size. Weekly intralesional injections with 4.0 x 10(6) units improved plaque
      consistency and decreased curvature and plaque size (P < 0.5). Overall subjective
      sexual performance was reportedly improved. Increased dosage of alpha INF-2B
      resulted in increased severity of flu-like symptoms when compared to the lower (1
      x 10(6) units) biweekly dosage. No significant difference was noted with the
      addition of oral Vitamin E therapy.

PMID- 11519220
TI  - Analysis of anesthesia practice and needs in Louisiana.
AB  - The Louisiana State University Health Sciences Center Department of
      Anesthesiology performed an analysis of anesthesia practice and needs within the
      State of Louisiana. The State of Louisiana currently has approximately 300
      practicing anesthesiologists (physicians), 700 certified registered nurse
      anesthetists (CRNAs), and does not currently utilize anesthesiologist assistants
      (AAs). Approximately 500,000 anesthesia encounters occur annually in Louisiana.
      Although there is a recognized critical shortage of anesthesiologists nationally,
      this document will focus mainly on the issue of mid-level providers of anesthesia
      services. The overwhelming majority of surgical and obstetric procedures is
      performed using the anesthesia care team approach both nationally and in the
      State of Louisiana. Within the anesthesia care team model, the practice of
      certified registered nurse anesthetists and anesthesiologist assistants are
      interchangeable, and both would meet the need for mid-level anesthesia providers
      in the State of Louisiana.

PMID- 11519221
TI  - [Sexual activity among adolescents and current solutions on our sexual
      education].

PMID- 11519222
TI  - [Health and sex education for groups of the population with special needs].

PMID- 11519223
TI  - [Psychosomatic disturbances in pubescent youth].

PMID- 11519224
TI  - [Novel low-dose contraceptive - one-year's experience with Logest].

PMID- 11519225
TI  - [Application of Remestip for genital hemorrhages in pubescent youth].

PMID- 11519226
TI  - [Products of Procter & Gamble for feminine personal hygiene: history and gamut.
      The sanitary napkin Always].

PMID- 11519227
TI  - [Genital hemorrhaging in children].

PMID- 11519228
TI  - [Contemporary stress on contraception for adolescents].

PMID- 11519229
TI  - [Family planning - decisive factor for health and reproductive opportunities for
      adolescents].

PMID- 11519230
TI  - [Surgically treatable epilepsy--a review].
AB  - 20-25% of epileptic patients do not become seizure free on adequate drug therapy.
      In 25-50% of patients with intractable epilepsy, the brain area responsible for
      seizures is well localizable and does not involve eloquent regions. In these
      patients, the surgical excision of the epileptic focus may lead to relief from
      seizures. In Hungary, there may be 5-6000 patients who needs an epilepsy surgery,
      but till now only 200 patients with chronic epilepsy underwent a surgical
      procedure. In the surgically remediable epilepsies, the operation is not a
      "ultima ratio". Concerning these syndromes, if 2-3 adequate antiepileptic drugs
      do not lead to seizure freedom within 1-3 years after the epilepsy onset, then a
      presurgical evaluation is necessary. The most common surgically remediable
      epilepsy is the temporal lobe epilepsy in which 60-90% of drug-resistant patients
      could be surgically cured. In lesional neocortical epilepsies 50-80% of patients
      become postoperatively seizure free. In childhood hemispheric epilepsies, the
      surgery could lead to seizure freedom in 70-80% of patients. The basic tools of
      the presurgical evaluation are the detailed history, the high resolution-MRI, the
      video-EEG monitoring, and the neuropsychological assessment. These investigation
      methods are usually enough to evaluate the necessity of the surgery and the
      postoperative outcome as well as to plan the localization and the extension of
      the resection. In some cases, ictal SPECT, PET, or video-EEG monitoring with
      intracranial electrodes could also be necessary in order to localize the
      epileptic focus.

PMID- 11519231
TI  - [The role of alimentary oxidants and antioxidants in carcinogenesis].
AB  - Malignancies have a distinguished role among leading causes of death around the
      world. As a result of more effective preventive efforts of cardiovascular
      diseases malignancies will reach the top of death statistics in the near future.
      The increased incidence of malignant tumors may be attributed to smoking, in
      temperate alcohol abuse, as well as inappropriate nutrition. Inappropriate
      nutrition is thought to be responsible for the development of about 30-50% of
      malignancies. In the present review the authors analyze the uniform theory of
      carcinogenesis and the possible mechanisms by which certain nutritive factors may
      interfere with the complex process of carcinogenesis. The mechanism of "oxidative
      stress" is detailed, in particular the impact of prooxidants (also referred to as
      free radicals) on tumor development and the central role of lipid peroxidation.
      In addition to alimentary free radicals the relevance of alcohol abuse in
      carcinogenesis is also studied. Against the undesirable free radical reactions a
      complex natural antioxidant (free radical scavenger) system exists, that is
      responsible for anticarcinogenesis. The authors introduce the dietary
      antioxidants, their known effects of mechanisms, and their possible role in
      chemoprevention and therapy of malignancies, based on several experimental and
      epidemiological data.

PMID- 11519232
TI  - [Plasma homocysteine levels in patients with ischemic heart disease].
AB  - In the latest years it became clear that beside traditional cardiovascular risk
      factors the high plasma homocysteine level increases the risk of atherosclerotic
      diseases too. Metaanalysis of 27 papers found that 10% of population's coronary
      risk is attributable to homocysteine and a 5 mumol/l increase in its plasma level
      elevates the coronary risk by as much as 0.5 mumol/l cholesterol increase. Recent
      studies have shown an inverse relation between the levels of plasma homocysteine
      and that of folic acid, vitamin B6, vitamin B12. The latters are cofactors and
      substrates of the homocysteine and methionin metabolism. The plasma total
      cholesterol, HDL-cholesterol, triglyceride, lipoprotein(a), Apo A1, Apo B and
      homocysteine concentrations were examined in 39 patients suffering from coronary
      artery disease treated in the Cardiac Rehabilitation Department of our hospital.
      Twenty of them were treated by folic acid and vitamin B6 for a three week period.
      The mean (+/- SD) plasma homocysteine concentration was 15.60 +/- 6.14 mumol/l.
      In the treated subgroup the mean (+/- SD) plasma homocysteine concentration was
      17.3 +/- 7.00 mumol/l, the mean (+/- SD) plasma folic acid level was 8.58 +/- 4.6
      mumol/l. After the three week treatment period (folic acid and vitamin B6) the
      plasma homocysteine level decreased by 26.5% (p = 0.012), that of folic acid
      increased by 68.7% (p = 0.002). From the plasma lipids the level of total- and
      LDL-cholesterol decreased significantly (6.7% and 10.4%, P < 0.05), caused by the
      strict diet during hospital treatment. As for the genetic polymorphism of the
      V677 gen of the metylenetetrahydrofolate-reductase (MTHFR) enzyme there was a
      significant correlation with homocysteine level (r = 0.436, p = 0.010), and a
      negative, but not significant correlation with the folic acid level (r = -0.354).

PMID- 11519233
TI  - [Intermediate results of surgical bladder augmentation in children].
AB  - The most common origin of the urinary incontinence are the myelodysplasia and
      congenital urogenital malformations in childhood. Surgical augmentation of the
      urinary bladder with or without continent diversion, may be indicated in case of
      unsatisfactory result of all other conservative treatments. Between 1987-2000
      bladder augmentation or substitution was carried out with large bowel or gastric
      segment in 37 patients. The age at surgery was between 6-21 yrs, (mean 12.3 yrs).
      The authors discuss the results of the 30 patients in whom follow up was at least
      1 yr (12-113 months, mean 43 months). The urinary incontinence could be solved in
      24/30 of the children, 6/30 remained in the same condition without worsening any
      of them. In 11/30 patients complication was not observed at all, but in 19/30
      further surgeries were necessary in 30 times, mainly due to stone formation. The
      authors state that the augmentation cystoplasty is a useful method for the
      creation of a low pressure urinary reservoire which with or without a continent
      diversion may solve the urinary incontinence, however the patients need a
      lifelong follow-up due to the possible long-term risks.

PMID- 11519234
TI  - [Selection from the history of cataract surgery from 2640 B.C. to 1750 A.D].

PMID- 11519235
TI  - [Methods of staging in colorectal cancers].

PMID- 11519236
TI  - Estimated coronary heart disease attributable to insulin resistance in
      populations with and without type 2 diabetes mellitus.
AB  - OBJECTIVE: To estimate the annual number and costs of coronary heart disease
      (CHD) events in the United States attributable to insulin resistance among
      individuals with and without type 2 diabetes. RESEARCH DESIGN AND METHODS:
      Medline-indexed articles and government statistical reports were screened for
      data on the prevalence of insulin resistance, the relative risk of CHD by insulin
      resistance status, and number of CHD events per year among individuals with and
      without type 2 diabetes. These data were used to estimate the number of CHD
      events per year by insulin resistance and type 2 diabetes status, the proportion
      of CHD events attributable to insulin resistance, and the annual cost of these
      events. RESULTS: Of the 171,000 annual CHD events in the type 2 diabetes
      population, 164,000 (96%) occurred in those with insulin resistance, 80,000 of
      which were attributable to insulin resistance. Of the 929,000 annual CHD events
      in the non-type 2 diabetes population, 162,000 (17%) occurred in patients with
      insulin resistance, 58,000 of which were attributable to insulin resistance.
      Thus, insulin resistance is responsible for 46.8%, 6.2%, and 12.5% of the annual
      CHD events in the type 2 diabetes, non-type 2 diabetes, and total US population,
      respectively. The estimated annual total cost of these insulin resistance
      attributable events was $12.5 billion in the United States in 1999, of which $6.6
      billion were direct medical costs. CONCLUSION: Preventing or modifying insulin
      resistance may reduce the morbidity, mortality, and costs associated with CHD.

PMID- 11519237
TI  - Hospice use in Medicare managed care and fee-for-service systems.
AB  - OBJECTIVE: To examine whether patterns of hospice use by older Medicare
      beneficiaries are consistent with the differing financial incentives in Medicare
      managed care (MC) and fee-for-service (FFS) settings. Specifically, are use
      patterns consistent with incentives that might encourage hospice use for MC
      enrollees and discourage hospice use for FFS enrollees? STUDY DESIGN: One-year
      study of hospice use by Medicare beneficiaries dying in 1996. PATIENTS AND
      METHODS: Medicare enrollment and hospice administrative data were used to examine
      hospice use before death for all elderly individuals residing in 100 US counties
      with high MC enrollment in 1996. Age-, sex-, and race-adjusted rate of hospice
      use and length of stay in hospice are compared between FFS and MC enrollees
      across and within (when possible) the 100 counties. RESULTS: Rates of hospice use
      were significantly higher for MC enrollees than for FFS enrollees (26.6 vs 17.0
      per 100 deaths; P < .001). These differences persisted within age, sex, and race
      groups but were not related to area MC enrollment rate or the amount of money
      paid to managed care organizations. Age-, sex-, and race-adjusted differences
      were observed in 94 of 100 counties. Length of stay in hospice was marginally
      longer for MC enrollees than for FFS enrollees (median, 24 vs 21 days; P <
      .0001). CONCLUSIONS: System of care is an important determinant of hospice use in
      the elderly Medicare population.

PMID- 11519238
TI  - A randomized trial of nurse specialist home care for women with high-risk
      pregnancies: outcomes and costs.
AB  - OBJECTIVE: To examine prenatal, maternal, and infant outcomes and costs through 1
      year after delivery using a model of prenatal care for women at high risk of
      delivering low-birth-weight infants in which half of the prenatal care was
      provided in women's homes by nurse specialists with master's degrees. STUDY
      DESIGN: Randomized clinical trial. PATIENTS AND METHODS: A sample of 173 women
      (and 194 infants) with high-risk pregnancies (gestational or pregestational
      diabetes mellitus, chronic hypertension, preterm labor, or high risk of preterm
      labor) were randomly assigned to the intervention group (85 women and 94 infants)
      or the control group (88 women and 100 infants). Control women received usual
      prenatal care. Intervention women received half of their prenatal care in their
      homes, with teaching, counseling, telephone outreach, daily telephone
      availability, and a postpartum home visit by nurse specialists with physician
      backup. RESULTS: For the full sample, mean maternal age was 27 years; 85.5% of
      women were single mothers, 36.4% had less than a high school education, 93.6%
      were African American, and 93.6% had public health insurance, with no differences
      between groups on these variables. The intervention group had lower fetal/infant
      mortality vs the control group (2 vs 9), 11 fewer preterm infants, more twin
      pregnancies carried to term (77.7% vs 33.3%), fewer prenatal hospitalizations (41
      vs 49), fewer infant rehospitalizations (18 vs 24), and a savings of more than
      750 total hospital days and $2,496,145 [corrected]. CONCLUSION: This model of
      care provides a reasoned solution to improving pregnancy and infant outcomes
      while reducing healthcare costs.

PMID- 11519239
TI  - Prevalence, costs, and treatment of Alzheimer's disease and related dementia: a
      managed care perspective.
AB  - BACKGROUND: The number of patients with Alzheimer's disease (AD) and related
      dementia treated in managed care organizations (MCOs) is increasing, and this
      trend is expected to continue. Therefore, it is critical that MCOs develop
      disease management strategies for this population. OBJECTIVE: To review the
      literature on the prevalence, costs, and treatment of AD and related dementia.
      STUDY DESIGN: Review of published articles from MEDLINE and peer-reviewed
      journals. RESULTS: Prevalence of AD and related dementia is approximately 5.7%
      among those aged 65 and older. Prevalence data from claims-based studies of AD in
      managed care are lower, ranging from 0.55% to 0.83%. Costs for formal care
      average $27,672 per patient annually, with long-term care being the most costly
      component. Annual costs for informal care are estimated to be $10,400 to $34,517
      per patient. Additional costs associated with AD include lost wages and
      productivity of patients and caregivers and costs associated with increased
      morbidity of caregivers. Donepezil treatment is well tolerated and has been
      extensively tested and evaluated in clinical settings. Early diagnosis and
      treatment of AD with donepezil has been shown to slow cognitive decline in AD.
      Although study findings regarding the cost offsets of donepezil-treated patients
      to date are mixed, there is a growing body of evidence to support the inclusion
      of this and other therapies into an MCO's AD treatment armamentarium.
      CONCLUSIONS: It is unlikely that MCOs will escape the increased prevalence and
      costs associated with AD. Opportunities exist through patient management programs
      targeted toward early diagnosis, effective use of medications, control of
      comorbidities, and patient and family support to partially offset these costs
      while providing quality patient care.

PMID- 11519240
TI  - Healthcare ethics committees and managed care.
AB  - OBJECTIVES: Healthcare ethics committees (HECs) play an important role in medical
      decision making in US hospitals, but no study has determined whether HECs deal
      with managed care, in any form. This pilot study was performed to evaluate the
      activities and perceptions of HECs about managed care. STUDY DESIGN: Forty-five
      hospitals in the Philadelphia area were selected at random, and comprised 36.6%
      of area institutions and 47% of area inpatient beds. Surveys were administered to
      ethics committee representatives by the authors in 1998. PATIENTS AND METHODS:
      Survey responses were coded, and both tabulated responses and analyzed data are
      presented. Correlations were analyzed with the unpaired 2-tailed t test. RESULTS:
      HECs devoted 7.6% of committee time to managed care issues, and the remainder to
      education, policy development, and case consultation. Time spent on managed care
      issues depended on the size of the institution (small hospitals spent twice the
      time on managed care as did large institutions); composition of the committee
      (presence of clergy and retirees on HECs correlated with the likelihood that HECs
      would address managed care issues); and whether the HEC was requested to help
      with managed care issues. Of the HECs surveyed, 18% had formal but disparging
      discussions of ethical concerns in managed care. The impact of changing insurance
      programs on the hospital and HECs was a concern. CONCLUSIONS: HECs arbitrate
      ethical conflicts in managed care when asked. As the presence of managed care
      increases, ethics committees will increasingly be called on to resolve the
      resulting ethical dilemmas. To be effective in this role, HECs must become
      knowledgeable about managed care principles and policies.

PMID- 11519241
TI  - Managed care can make a difference: the need for care at the end of life.

PMID- 11519242
TI  - [Effect of ascorbic acid on the oxidative homeostasis of skin].

PMID- 11519243
TI  - [Role of biologically active substances in the formation of cardiogenic reflex
      effects on circulation].
AB  - Analysis of the literary and own authors data about the participation some
      endogenous bioregulators (prostacyclin, bradykinin, nitric oxide) in the
      cardiogenic depressor reflexes formation is represented in this review.
      Possibility of chemosensitivity of the vagal afferent fibers for this substances
      and its role in the formation of cardiogenic effects on circulation is discussed.

PMID- 11519244
TI  - [Testosterone modulation of HERG potassium channel blockade induced by
      neuroleptics].
AB  - The repolarisation phase of cardiac action potential is characterized by sexual
      dimorphism suggesting the role of sex steroid hormones in the regulation of K+
      channels. Here we report on the effect of testosterone on blockade of HERG
      encoded K+ channels induced by neuroleptics. These compounds are used in clinics
      to treat psychiatric disorders, but reportedly have proarrhythmic side effects,
      on HERG-encoded K+ channels responsible for the rapid component of cardiac
      delayed rectifier K+ current, IKr. HERG was expressed in Xenopus oocytes, HERG
      expressing oocytes were preincubated in 1 microM of testosterone from 3 to 8
      hours before experiments. The extent of the blockade by neuroleptics in control
      oocytes increased with depolarization correlating with channels activation
      consistent with open-channel blocking mechanism. The IC50 and A (maximal block)
      values for the haloperidol-, pimozide- and fluspirilen-induced blockade of fully
      activated IKr were 1.36 microM and 73%, 1.74 microM and 76%, 2.34 microM and 65%
      respectively. Testosterone decreased extent of maximal block and significantly
      diminished block voltage-dependance of IKr inhibition, it also decreased the
      efficiency of block, with IC50 and A values of 2.73 microM and 65%, 2.08 microM
      and 59%, 5.04 microM and 64% for haloperidol, pimozide and fluspirilen
      respectively. Testosterone treatment increased IC50 and decreased A for all three
      agents. The largest decrease in A was with pimozide and the largest increase in
      IC50 was with fluspirilen. Our results suggest protective role of testosterone
      (androgens) against proarrhythmic side effects of some compounds.

PMID- 11519245
TI  - [cGMP-independent effect of nitric oxide on contractility and intracellular
      calcium level of rat tail artery vascular smooth muscles].
AB  - The effects of nitric oxide (NO, 10(-6) M) on contractility and intracellular
      calcium level ([Ca2+]i) of rat tail artery smooth muscles in control and under
      inhibition of soluble guanylate cyclase (sGC) with 6-anilino-5,8-quinolinedione
      (LY83583, 10(-6) M) are investigated. NO-induced relaxations of vascular smooth
      muscles comprised 61.01 +/- 5.56% of maximum induced amplitude of K(+)
      contracture, and decreases in [Ca2+]i comprised 66.35 +/- 11.33%. Under the
      inhibition of sGC with LY83583 NO-induced relaxations of vascular smooth muscles
      comprised 29.41 +/- 5.17% of maximum induced amplitude of K(+)-contracture, and
      decreases in [Ca2+]i comprised 53.68 +/- 16.93%. Thus, cGMP-independent
      relaxation of vascular smooth muscle and decrease in [Ca2+]i of rat tail artery
      is confirmed.

PMID- 11519246
TI  - [Mechanisms of the effect of circulating neutrophils (granulocytes) in the
      response of a release reaction of human platelets].
AB  - Studied singularities of development platelet release reaction, as of functional
      activity platelets, at direct effect contents of cytoplasmic granular structures
      circulating neutrophile leucocytes (granulocytes), possessing a potential
      capability to selective exocytosis. The model researches were conducted in a
      system in vitro on isolated viable non active of platelets practically of healthy
      people. As possible activators the subpopulations them of cytoplasmic granules,
      distinguished on morphological and enzymetion to indications were applied,
      previously chosen by methods of an analytical centrifuging from donor neutrophile
      granulocytes. The development platelets of a response of a release was determined
      on dynamics quantitative reorganization in platelets an alpha-granules and change
      of activity in out of platelets to environment of the factor 4 platelets. The
      capability of a dominance lysosomal initiators neutrophile granulocytes in
      development of a response of a release of platelets was installed. The scheme of
      probable trigger participation circulating of neutrophile granulocytes in
      development syndrome disseminated intravascular coagulation.

PMID- 11519247
TI  - [Effect of nitric oxide on force-frequency relations in experimental
      hyperfunction and hypertrophy in the heart muscle].
AB  - The influence of nitric oxide--NO on force-frequency relations in normal and
      hypertrophy rats isolated papillary muscles were compared using isometric force
      measurement. Stimulation frequency varied between 0.33 and 3 Hz. In normal
      conditions rat papillary muscle exhibit a negative force-frequency staircase,
      which is different from hypertrophy ventricular preparations (force-frequency
      relations practically be absent). During the incubation of hypertrophy
      ventricular preparations in nitro-glycerinem-containing solution (NO donator) the
      force-frequency relations measured on these muscles display the same behaviour as
      in normal conditions. The application of a caffeine into the bath solution
      abolishes a negative force-frequency staircase in all bunches of experiments.
      Under durable infusion of NO-predecessor--L-arginine to the rats (100 mg/kg) with
      hypertrophy of heart, the papillary muscle exhibits a positive force-frequency
      staircase. Caffeine did not caused any changes in force-frequency relations on
      rats ventricular preparations in there conditions. We conclude that the
      paradoxical response of hypertrophy of hearts is connected to infringements of
      redistribution of ions Ca between extracellular medium and intracellular stores
      in a systole and diastole.

PMID- 11519248
TI  - [Effect of p-chloromercuribenzoic acid and dithiothreitol on the Ca(2+) content
      of salivary glands and their protein secretion].
AB  - It has been shown, less concentrations of p-chlormercuribenzoate (1 and 2.5 mM)
      increased Ca2+ content in gland tissue and thereby protein secretion level that
      may occurred mainly by suppression Ca(2+)-pump or/and stimulation of Na(+)-Ca(2+)
      exchange (both in cell plasma membrane) through modulation of SH-groups which
      form part of their molecules. Higher PCMB concentrations markedly decreased Ca2+
      content in gland tissue as well as protein secretion. Effects of PCMB (5 and 10
      mM), depending on the direction of Na(+)-Ca(2+)-exchange functioning (Ca(2+)
      efflux or Ca(2+)-influx), were evoked or presumably by suppression of endoplasma
      reticulum Ca(2+)-pump (at conditions Na(+)-dependent Ca(2+)-efflux) or Na(+)
      dependent Ca(2+)-influx into the cells that clearly confirmed when PCMB was added
      on the background of eosin Y (specific Ca(2+)-ATPase inhibitor). Possible role of
      potential dependent Ca(2+)-channnels in the mediating of PCMB effects is
      discussed. Introducing of dythiothreitol (DTT) increased Ca2+ content in glands
      and decreased secretion level obviously by protection of SH-groups of cell Ca(2+)
      transporting systems and thereby diminished [Ca2+]i. Finally, we confirm
      important functional role of SH-groups in the regulation of Ca(2+)-homeostasis in
      secretory cells of exocrine glands.

PMID- 11519249
TI  - [Biological activity characteristics of the complex of peptide fragments of
      hemoglobin].
AB  - There were studied the influence of hemoglobin peptide complex in different doses
      on indexes of systemic hemodynamics, ECG and visually cased potentials in healthy
      animals. In the dose of 10 mg/kg the peptide complex rolonged the time of the
      course of depolarization and repolarization processes on the miocardial
      ventricles with the increase of the systolice blood volume. In the dose of 1
      mg/kg the introduction of the peptide complex accelerated the conductiong of
      visual madality stimuli on the specific afferent systems subcortex and cortex
      divisions of visnal analyzer.

PMID- 11519250
TI  - [Content of myocardial catecholamines in patients with natural and acquired heart
      disease].
AB  - Approved by increased considered of adrenaline and nor-adrenaline in myocard of
      patients with native and acquisition of the heart diseases a speciality at part
      of the heart with largest functional working load. Taking increased levels of
      adrenaline and nor-adrenaline in the different parts of the heart at the sever
      patients with heart diseases usually with progressive heart's decompensation the
      recommendation preventive cardio-stimulation of the time of the surgery operation
      on the heart for correction of cardiac arrhythmic.

PMID- 11519251
TI  - [Study on the connection of alcohol motivation with zinc content changes in the
      hippocampus].
AB  - Alcohol dependence development is accompanied by zinc content decrease in the
      hippocampus. Young age, repeated physical loads and immobilization are factors,
      that promote such changes development in more expressed degree.

PMID- 11519252
TI  - [Significance of the activity of indicators of the fibrinolytic system on
      assessment of the hemostatic state].
AB  - Complex analysis of pregnant women haemostasis system before and after caesarian
      section allowed find the coagulation system activation. It was shown the
      thrombotic markers accumulation, AT III and protein C levels decrease. Also
      change of ratio fibrinolytic system components was exposed. Definition of t-PA
      and PAI-1 activities can be used as prognostic markers of the fibrinolytic chain
      haemostasis system disfunction.

PMID- 11519253
TI  - [State of mitochondrial respiration and calcium capacity in livers of rats with
      different resistance to hypoxia after injections of L-arginine].
AB  - In experiments on rats with different resistance to hypoxia are investigated
      processes of mitochondrial respiration, oxidative phosphorylation and calcium
      capacity in liver under precursor nitric oxide L-arginine (600 mg/kg) and
      blockator nitric oxide synthase L-NNA (35 mg/kg) injections. We are used next
      substrates of oxidation: 0.35 mM succinate, 1 mM alpha-ketoglutarate, 1 mM alpha
      ketoglutarate and 2 mM malonic acid. Increasing of ADP-stimulation respiration
      states under exogenous L-arginine injection, decreasing efficacy of respiration
      processes (respiration control on Chance and ADP/O) under such substrates
      oxidation, testify to oxide energy support decreasing and reversing nitric oxide
      inhibit in such conditions. This will be used as mechanism cell regulation
      succinate dehydrogenase activity. It has shown that L-arginine injection increase
      calcium mitochondrial capacity low resistance to hypoxia rats using substrates of
      oxidation succinate and alpha-ketoglutarate to control meanings of high
      resistance rats. Effects of nitric oxide precursor influence on this processes
      limit NO-synthase inhibitor L-NNA.

PMID- 11519254
TI  - [Functional properties of cooperative monoclonal antibodies against human tumor
      necrosis factor].
AB  - The panel of 23 newly produced monoclonal antibodies (mAbs) against human tumor
      necrosis factor (TNF) was examined for enhanced or cooperative TNF binding.
      Epitopic mapping revealed a preferential mAb generation against two epitopes
      designed as A1 and C1. Both A1 and C1 mAbs have neutralizing activity and display
      remarkable property to bind TNF synergistically comprising a pair of cooperative
      mAbs. C1 epitope resides within the TNF receptor-binding site (RBS) and
      responsible for generation of competitive neutralizing mAbs that block TNF
      activity by direct RBS masking. RBS-distal A1 epitope represents allosteric
      neutralizing mAbs that block TNF activity by conformational RBS changes.
      Combination of A1 and C1 mAbs resulted in synergistic TNF neutralization through
      complementary effect of competitive and allosteric TNF blocking mechanisms.
      Generation of cooperative Abs may have significance to achieve the most efficient
      neutralization of protein antigens with an intolerable functional activity in
      vivo.

PMID- 11519255
TI  - [Differences in maximal aerobic capacity for athletes conditioned by direction in
      the long-term adaptation process].
AB  - On the basis of investigation of 54 elite male athletes aged 19-24, specializing
      in different running distances (100, 800 and 5000 m), the influence of specific
      character of long-term adaptation in the body of athletes on general level of
      aerobic power and conditions of maximum manifestation of cardiorespiratory system
      aerobic capacity was demonstrated. The determine maximum level of aerobic
      capacity in the athletes, motor tests that take into account the features of
      maximum aerobic capacity mobilization conditions due to specifics of sports
      specialization were selected.

PMID- 11519256
TI  - [Characterization of the functional motility of nervous processes of machinist
      class railway operators].
AB  - The relationship of functional motility of nervous processes (FMNP) with a
      professional rating of the operators of dynamic systems (engineman) was
      researched. The analysis of asymmetry sensory-motor responses was carried out.
      The examination 213 engineman was carried out. Professionally successful
      engineman are characterized more high level FMNP. The level of parameter FMNP 110
      stimuli in one minute allows from 85% by accuracy to forecast professional
      successful of engineman. The relationship of dynamics of change of a response
      time of a right and left hand is detected during fulfillment of the test with
      professional successful. These data are expedient for using at professional
      psychophysiological selection.

PMID- 11519258
TI  - Progress towards laboratory containment of wild polioviruses, June 1999-June
      2001.

PMID- 11519257
TI  - [Effect of an erythrocyte peptide extract on indexes of lipid peroxidation,
      antioxidant protection and hemostasis of animals exposed to fractionated doses of
      gamma-ray irradiation].
AB  - We have studied the influence of the erythrocite peptide extract on the
      functional condition of the indexes of the lipid peroxide oxidation and
      antioxidant protection and haemostasis, as the composite adaptational reactions,
      in two series of guinea-pigs, which were exposed to the fractions dosed gamma
      rays irradiation for 6 days (on 1 Gr per day). The visible effect was observed in
      guinea-pigs, which had injection of the erythrocite peptid extract not
      immediately after 6-days exposure fractions gamma-rays radiation, but in 12 days.

PMID- 11519259
TI  - Access to biomedical journals.

PMID- 11519260
TI  - Outcome focus thinking--getting results without the boxing gloves.

PMID- 11519261
TI  - The new economy and new union organizing strategies: union wins in healthcare.

PMID- 11519262
TI  - Restraint reduction in a large tertiary medical center.

PMID- 11519263
TI  - Instruments for evaluating nurse competence.

PMID- 11519264
TI  - Lack of power and influence.

PMID- 11519265
TI  - An approach for systems analysis of patient care operations.
AB  - A healthcare landscape characterized by cost pressures, advancing technologies,
      staffing shortages, and increasing regulation is the norm for nursing leaders.
      High performance in these environments requires effective operational structures.
      These structures must respond to change while maintaining operational stability.
      An approach to assist nursing leaders in systemic analysis of operational
      structure is presented here. The approach helps leaders to identify structural
      inadequacies that limit operational performance.

PMID- 11519266
TI  - Creating a future worth experiencing: nursing strategic planning in an integrated
      healthcare delivery system.
AB  - The application of a strategic planning methodology for the discipline of nursing
      is described in use by a large, nonprofit integrated healthcare system. The
      methodology uses a transformational leadership assessment tool, quality planning
      methods, and large group intervention to engage nurses in the implementation of
      strategies. Based on systems theory, the methodology outlined by the author has
      application at any level in an organization, from an entire delivery network, to
      a patient care unit. The author discusses getting started on a strategic planning
      journey, tools that are useful in the process, integrating already existing
      business plans into the strategies for nursing, preliminary measures to monitor
      progress, and lessons learned along the journey.

PMID- 11519267
TI  - Simulation software: engineer processes before reengineering.
AB  - People make decisions all the time using intuition. But what happens when you are
      asked: "Are you sure your predictions are accurate? How much will a mistake cost?
      What are the risks associated with this change?" Once a new process is
      engineered, it is difficult to analyze what would have been different if other
      options had been chosen. Simulating a process can help senior clinical officers
      solve complex patient flow problems and avoid wasted efforts. Simulation software
      can give you the data you need to make decisions. The author introduces concepts,
      methodologies, and applications of computer aided simulation to illustrate their
      use in making decisions to improve workflow design.

PMID- 11519268
TI  - Educational needs of nurse administrators in the Middle East.
AB  - A collaborative research project was conducted by using a framework based on the
      11 management functions as defined by the WHO (World Health Organization), to
      determine the educational needs of directors of nursing in ministry of health
      hospitals in Saudi Arabia. The results of this study can be used to guide
      effective and cost-efficient transfer of nursing knowledge throughout the Middle
      East.

PMID- 11519269
TI  - How well prepared are we?

PMID- 11519270
TI  - An ethicist's commentary on shooting farmed deer.

PMID- 11519271
TI  - Comparison of 2 techniques for regional antibiotic delivery to the equine
      forelimb: intraosseous perfusion vs. intravenous perfusion.
AB  - The purpose of this study was to compare the synovial fluid concentrations and
      pharmacokinetics of amikacin in the equine limb distal to the carpus following
      intraosseous and intravenous regional perfusion. The front limbs of 6 horses were
      randomly assigned to either intraosseous or intravenous perfusion. A tourniquet
      was placed distal to each carpus and the limb perfused with 500 mg of amikacin.
      Systemic blood samples and synovial fluid samples were collected over 70 min from
      the distal interphalangeal (DIP) joint, metacarpophalangeal joint, and digital
      flexor sheath. The tourniquet was removed following the 30 min sample collection.
      The mean peak amikacin concentration for the DIP joint was significantly higher
      with intravenous perfusion. There were no significant differences in time to peak
      concentration or elimination half-life between methods at each synovial
      structure. Each technique produced mean peak concentrations ranging from 5 to 50
      times that of recommended peak serum concentrations for therapeutic efficacy.

PMID- 11519272
TI  - [Comparison of direct smear observations and bacteriologic culture results
      carried out on equine tracheal secretions].
AB  - The aim of the study was to assess the relation between the direct smear
      observations and bacteriological results carried out on equine tracheal
      secretions. A total of 304 cases comprising both the direct smear (Gram stain)
      and the bacteriological culture, over a period of 8 years, were submitted to this
      retrospective study. Most of the specimens (78%) were obtained using tracheal
      washings while the rest (22%) originated from tracheal brushings. A total of 96
      specimens (32%) were negative for both direct smear and culture. The positive
      predictive value of direct smears appeared high (81-96%) while the negative
      predictive value was lower (48-79%). Sensitivity of direct smear was considered
      as low and varied from 24 to 46% for tracheal brushings and from 41 to 46% for
      tracheal washings. Specificity of direct smear was high for both types of
      specimens. Results of this study indicate that the use of Gram-stained smear
      examination, carried out on tracheal secretions, is a technique which is specific
      but not very sensitive for the prediction of bacteriological culture results.
      Moreover, the use of tracheal washing, more than tracheal brushing, seems to
      increase the sensitivity of the test.

PMID- 11519273
TI  - Effect of acrosomal defects on fertility of bulls used in artificial insemination
      and natural breeding.
AB  - Four bulls that produced spermatozoa with a high percentage of abnormal acrosomes
      were individually placed in pens with females for 21 days. Frozen semen from 2 of
      the bulls was used for artificial insemination. One of the bulls was placed in a
      competitive mating situation with normal bulls at pasture. First service
      pregnancy rates were determined by transrectal ultrasonography 28 days after bull
      removal from breeding pens, or after the last artificial insemination. The
      results of competitive mating at pasture were determined from breeding
      observations, the phenotypic characteristics of calves sired, and blood typing
      for parentage. The results of these studies suggest that bulls that produce a
      high percentage of spermatozoa with indented acrosomes may have normal fertility
      when used in artificial insemination or in single sire mating; however, their
      fertility may be low when breeding competitively with bulls with normal
      spermiograms.

PMID- 11519274
TI  - Congenital mastocytomas in a Holstein calf.
AB  - Congenital defects occur infrequently in cattle. In this report, a stillborn
      Holstein calf was presented for unusual nodules in the skin. Necropsy and
      histopathologic findings aided in the diagnosis of systemic mastocytoma, or mast
      cell tumor. The diagnosis of congenital mastocytoma in this case is extremely
      rare and unique.

PMID- 11519275
TI  - The state of the ecosystem on Anticosti Island, Quebec.
AB  - The state of the ecosystem of Anticosti Island, Quebec, was studied by veterinary
      students (n = 17) and faculty (n = 4) in the summer of 1999. The field of
      ecosystem health is an integrative science requiring the expertise of
      professionals in several disciplines, including socioeconomic, ecological,
      biophysical, human health, and animal health (1).

PMID- 11519276
TI  - "Grosse-Ile": an overview of the island's past role in human and animal medicine
      in Canada.

PMID- 11519277
TI  - Compensating your associate--does pay for performance work for both associate and
      owner?

PMID- 11519278
TI  - Malnutrition-induced cataracts in an orphaned kitten.

PMID- 11519279
TI  - Postoperative physical therapy in orthopedic patients.

PMID- 11519280
TI  - Diagnostic ophthalmology. Melting corneal ulcer.

PMID- 11519281
TI  - Psychosomatic disorders in pediatrics.
AB  - Psychosomatic symptoms are by definition clinical symptoms with no underlying
      organic pathology. Common symptoms seen in pediatric age group include abdominal
      pain, headaches, chest pain, fatigue, limb pain, back pain, worry about health
      and difficulty breathing. These, more frequently seen symptoms should be
      differentiated from somatoform or neurotic disorders seen mainly in adults. The
      prevalence of psychosomatic complaints in children and adolescents has been
      reported to be between 10 and 25%. These symptoms are theorized to be a response
      to stress. Potential sources of stress in children and adolescents include
      schoolwork, family problems, peer pressure, chronic disease or disability in
      parents, family moves, psychiatric disorder in parents and poor coping abilities.
      Characteristics that favour psychosomatic basis for symptoms include vagueness of
      symptoms, varying intensity, inconsistent nature and pattern of symptoms,
      presence of multiple symptoms at the same time, chronic course with apparent good
      health, delay in seeking medical care, and lack of concern on the part of the
      patient. A thorough medical and psychosocial history and physical examination are
      the most valuable aspects of diagnostic evaluation. Organic etiology for the
      symptoms must be ruled out. Appropriate mental health consultation should be
      considered for further evaluation and treatment.

PMID- 11519282
TI  - AIIMS clinical score: a reliable aid to distinguish neonatal hepatitis from extra
      hepatic biliary atresia.
AB  - It is important to distinguish neonatal hepatitis (NH) from extra hepatic biliary
      atresia (EHBA) in a neonate presented with jaundice as the former is purely
      medical management and the latter requires surgical procedure at the earliest.
      The observations on the critical evaluation of the neonatal jaundice cases led us
      to propose AIIMS clinical score (ACS) and this retrospective study was designed
      to evaluate the reliability of the ACS in all the 120 babies with jaundice
      referred to the pediatric surgery department during the past 10 year period. The
      ACS described here is based on 5 clinical parameters--Age, Jaundice, Colour of
      urine and stool and Clinical examination of liver. The accuracy of the
      hepatobiliary scan (HBS) with respect to the diagnosis of EHBA in this series, as
      compared to per operative cholangiography (POC) which is considered as the gold
      standard to distinguish these conditions was only 68%. However, ACS showed a
      sensitivity of 91.5%, a specificity of 76.3%, positive predictive value of 89.2%,
      negative predictive value of 80.5% and an overall diagnostic accuracy of 86.6%.
      ACS is reliable to distinguish NH from EHBA at bedside.

PMID- 11519283
TI  - Prevalence of missed opportunities for measles immunization in rural areas of
      Gujarat.
AB  - To assess the prevalence of missed opportunities for measles immunization, reason
      for their occurrence and potential aspect of avoiding them on measles
      immunization coverage a cross sectional study in 40 clusters of 4 villages, Ardi,
      Valasan, Chikhodra and Bamroli having a population of twenty four thousand was
      carried out. A total of 300 children between the age group 9-24 months were
      included in the study. Immunization status of each child was recorded either from
      immunization card or maternal recall. Coverage for measles vaccine was 78.66%.
      Prevalence of missed opportunity was 15.33%. It was found that significant
      increase in measles coverage can be achieved upto 94% if all missed opportunities
      for measles vaccine are avoided.

PMID- 11519284
TI  - Capillary refill time in term neonates: bedside assessment.
AB  - Capillary refill time (CRT) is yet to be established as a specific clinical sign
      of peripheral circulation in neonates. This study was conducted to assess the
      influence of four body sites used for measurement, interobserver variability,
      sex, birth weight, age at assessment and room temperature on CRT recorded in
      healthy term neonates, at bedside. Two observers measured CRT in four different
      body sites (forehead, chest, palm and heel) of each of 155 healthy term neonates.
      Significant differences occurred between the mean CRT recorded by the two
      observers in forehead (mean +/- SD: 2.62 +/- 0.8 s and 1.88 +/- 0.57 s; p <
      0.001), palm (2.99 +/- 0.61 s and 2.75 +/- 1.12 s; p < 0.05) and heel (3.08 +/-
      0.79 s and 4.24 +/- 1.84 s; p < 0.001). Only CRT in chest (2.7 +/- 0.42 s and
      2.62 +/- 0.74 s) produced no significant differences in the means with a
      statistically significant and clinically fair, but not strong, interobserver
      agreement (r = 0.4; p < 0.001). No significant associations occurred between CRT
      and sex or birth weight. The associations of chest CRT with age at assessment (r
      = -0.23; p < 0.01) and room temperature (r = 0.27; p < 0.01) were clinically not
      important. In conclusion, CRT in neonates needs to be validated further before it
      can be useful as a specific clinical sign of peripheral circulation.

PMID- 11519285
TI  - Lipid profile in the progeny of parents with ischemic heart disease.
AB  - Lipid profile of 50 offsprings of parents with ischemic heart disease and 15
      control children aged 5-16 years was studied. The children in both the groups
      were categorized into 3 sub groups, 5-10, 11-15 & > 15 years. The Serum total
      cholesterol levels (mean +/- S.D) (in mg/dl) in the test group were 169.8 +/-
      15.13, 173.34 +/- 33.56, 177.4 +/- 27.89 respectively for the 3 age subgroups.
      The Serum LDL cholesterol levels (mean +/- S.D) (in mg/dl) in the test group were
      102.2 +/- 15.25, 95.13 +/- 30.38, 101.09 +/- 26.96 respectively. The serum total
      cholesterol levels (mean +/- S.D) (in mg/dl) in the control group were 123 +/-
      1.33, 118 +/- 7.51 and 127.4 +/- 5.77 respectively for the 3 age subgroups. The
      serum LDL cholesterol levels (mean + S.D) (in mg/dl) in the control group were
      56.64 +/- 8.75, 43.36 +/- 6.10 and 45.16 +/- 6.78 respectively. The serum total
      cholesterol and LDL cholesterol levels in the test group were significantly
      higher as compared to controls (p > 0.05). Among test subjects, 54% had elevated
      total cholesterol (> 170 mg/dl) and 38% had elevated LDL cholesterol (> 110
      mg/dl). These cases had a significant correlation with elevated parental total
      cholesterol and LDL cholesterol levels (p > 0.05). Thus, a selective screening of
      the offsprings of parents with premature ischemic heart disease and
      hypercholesterolemia is advocated.

PMID- 11519286
TI  - Clinical manifestations and management of pediatric HIV infection.
AB  - HIV infection has emerged as a colossal problem with epidemic proportions.
      According to an estimate from UNAIDS about 36.1 million people all over the world
      are infected at present. In India about 3.5 million people are infected. The
      infection has evolved into phase II process of disease evolution, spreading from
      high-risk population to the general population. The antenatal HIV seropositivity
      has shown a steady increase from 0.1% to 2% in some tertiary care hospitals in
      Mumbai. Pediatric HIV infection presents with diverse clinical manifestations. In
      developing countries like India, diagnosis of infection during first year of life
      in perinatally exposed infants poses a problem due to lack of easy accessibility
      and increased cost of diagnostic facilities like HIV-PCR, CD4/CD8 counts and
      viral cultures. Moreover, lack of adequate drugs and exorbitant cost of
      sustaining antiretroviral therapy complicates the management issues. An
      assortment of antiretovirals is available in USA and other developed countries.
      In India drugs like zidovudine, lamivudine, stavudine, nevirapine and indinavir
      are available and are used in symptomatic patients. CDC has defined definite
      treatment guidelines for pediatric population recently. These guidelines need to
      be modified in our set up. At the present juncture in India the emphasis remains
      on the prevention and treatment of opportunistic infections like tuberculosis and
      pneumocystis carinii and on prevention of perinatal transmission with zidovudine.
      This brief review deals with various clinical manifestations as relevant in a
      developing country like India and recent advances in antiretroviral therapy.

PMID- 11519287
TI  - Antiviral therapy: respiratory infections, chronic hepatitis.
AB  - This review focuses on the activity, clinical pharmacology, and clinical
      indications of antiviral agents used in the management of influenza, respiratory
      syncytial virus infections, and chronic hepatitis B and C. Two neuraminidase
      inhibitors, a new class of antiviral agents, were recently approved for the
      treatment of influenza A and B in children.

PMID- 11519288
TI  - Antiretroviral drugs in pediatrics.
AB  - The advent of potent drugs to treat HIV and the development of increasingly
      effective treatment strategies have resulted in dramatic improvements in the
      prognosis and quality of life for HIV-infected children. The purpose of this
      article is to provide the primary care physicians with practical information on
      antiretroviral drugs that are currently used for the treatment of pediatric HIV
      infection.

PMID- 11519289
TI  - Anti-herpes viruses agents.
AB  - Antiviral agents with demonstrated efficacy are currently available for the
      management of infections in children caused by the herpes viruses including
      herpes simples type 1 (HSV1) and type 2 (HSV2), varicella-zoster virus (VZV), and
      cytomegalovirus (CMV). Recently, progress has been made in the development of
      newer agents with enhanced activity against these viruses including resistant
      strains. This review focuses on the activity, clinical pharmacology, and clinical
      indications of antiviral agents used in the treatment of infections caused by the
      different herpes viruses in children.

PMID- 11519290
TI  - Systemic antifungal agents.
AB  - Anti-fungal agents are classified under two major headings, systematic and
      topical agents. Only systematic anti-fungal agents will be discussed in this
      chapter. Since the discovery in 1955, amphotericin B has been the cornerstone of
      anti-fungal treatment. It is active against most species of fungi. However,
      Candida lusitaniae, Pseudallescheria boydii, and fusarium spp have primary
      resistance to amphotericin B. Recently, new liposomal preparations of
      amphotericin B have been developed. They are less nephrotoxic. The azole family
      of anti-fungal includes two broad classes: the imidazoles (clotrimazote,
      ketoconazote, miconazole) and the triazoles (flucouazole and itracouazole).
      Imidazoles are still widely used for the treatment of superficial mycoses and
      vaginal candidiasis. The systematic triazoles are more slowly metabolized and
      have less effect on human synthesis than imidazoles, hence they are preferred for
      systemic therapy. Flucytosine is a fluorinated pyrimidine. Clinically, the
      principal use of flucytosine is as adjunctive therapy with amphotericin B in the
      treatment of candidial or cryptococcal diseases, Griseofuluin is derived from
      penicillium. It is fungistatic in vitro for species of dermatophytes. It is
      useful for the treatment of tinea capitis and tinea unginum.

PMID- 11519291
TI  - Hemiplegia and motor aphasia following scorpion sting.
AB  - Hemiplegia and motor aphasia are rare complications following scorpion sting.
      This report describes a case of hemiplegia and motor aphasia occurring in a young
      child, following a scorpion sting.

PMID- 11519292
TI  - Early onset mixed Morganella and Klebsiella sepsis in a neonate.
AB  - A premature baby girl was delivered vaginally to a mother who had an otherwise
      normal pregnancy, and spontaneous premature onset of labour. She had early onset
      neonatal sepsis with pneumonia. The baby's blood culture as well as the amniotic
      membrane culture grew Morganella and Klebsiella. She recovered on appropriate
      antibiotics. This is only the second reported case of early onset neonatal sepsis
      due to Morganella. The literature is reviewed.

PMID- 11519293
TI  - Transcatheter coil embolization of a traumatic intrahepatic arterioportal
      fistula.
AB  - Traumatic arterioportal fistulas are rare lesions in the pediatric age group.
      This case highlights the safe and effective management of intrahepatic
      arterioportal fistulas by transcatheter coil embolization.

PMID- 11519294
TI  - Survival after an acute pericardial tamponade as a result of percutaneously
      inserted central venous catheter in a preterm neonate.
AB  - Percutaneously inserted central venous catheters (PICC) are used in premature
      infants to deliver intravenous fluids, total parenteral nutrition (TPN) and
      medications. This article reports a case in which the baby developed pericardial
      tamponade within 3 hours of starting TPN through a PICC. This was successfully
      treated with percutaneous subxiphoid pericardiocentesis. Pericardial tamponade
      should be suspected in any infant with a PICC line in place, and who suddenly
      develops shock like symptoms, non-attributable to usual causes.

PMID- 11519295
TI  - "Porcine bronchus" diagnosed in neonatal period.
AB  - "Porcine bronchus" is a right upper lobe bronchus arising directly from the
      trachea. This is an infrequent congenital abnormality and it usually represents
      the displaced origin of a normal bronchus. We herewith report a case of a child
      who was diagnosed to have tracheal bronchus in neonatal period and followed
      subsequently until 13 months of age.

PMID- 11519296
TI  - Menetrier's disease.
AB  - An 8-year-old girl presented with persistent vomiting, pain abdomen and
      generalized edema. Barium studies and gastroscopy suggested hypertrophic
      gastropathy. Histopathological examination pointed the diagnosis towards
      Menetrier's Disease. There was spontaneous remission and the child required only
      supportive therapy.

PMID- 11519297
TI  - Antibiotic resistance among common bacterial enteric pathogens isolated from
      stool.

PMID- 11519298
TI  - Idiopathic pulmonary hemosiderosis.

PMID- 11519299
TI  - [Peripartal hysterectomy].
AB  - In the present investigation the authors review 37 cases of peripartal
      hysterectomy, made in our clinic for a 10 year period. The results show that
      there is a high risk intervention, because of the massive blood loss and altered
      anatomical structure.

PMID- 11519300
TI  - [Collection of a concentration of hematopoietic stem cells from the umbilical
      cord ].
AB  - Allogeneic Hematopoietic Stem Cells Transplantation is a therapy for wide variety
      of malignant and nonmalignant disorders. Cord blood as an alternative source of
      hematopoietic stem cells was utilized and these transplantations.

PMID- 11519301
TI  - [Implementation of Reid's colposcopic index in teenagers].
AB  - The aim of the present investigation was to determine the possibilities of the
      Reid's colposcopic index to diffentiate the grade of the findings in sexually
      active teenagers. MATERIAL AND METHODS: The study was based on 83 girls without
      child-birth in history, aged between 14 an 19 (mean age 18.13 years)q with
      different grade cytological and/or colposcopic atypia. Colposcopic findings were
      joined, according to semiobjective Reid's index and the results achieved were
      compared with the histological findings from the target biopsies. RESULTS AND
      DISCUSSION: The results from the colposcopic investigation were divided into 4
      groups: in group 0--without pathological findings were classified 12 cases, in
      gr. 1 (Reid)--42, in gr. 2 (Reid)--24 and in gr. 3 (Reid)--5 patients.
      Histological equivalents were summarized as follow: normal and papiloma
      epithelium--in 27, CIN I--in 36, CIN II--15q and CIN III--5 cases. CONCLUSIONS:
      The investigation performed, shows the good correlation (91.6%) between
      colposcopic impression and histological diagnosis, and this put the question
      about the place and role of the Reid's colposcopic index in predicting the
      severity of the pathological changes of the uterine cervix in sexually active
      adolescent girls.

PMID- 11519302
TI  - [Diagnostic modalities of endometrial ultrasonography in women with irregular
      bleeding in menopause].
AB  - The aim of the present study was to investigate the diagnostic possibilities of
      the endovaginal sonography for the assessment of the state of the endometrium in
      women with irregular bleeding in climax. MATERIALS AND METHODS: Fifty women
      between 40 to 60 years (mean 47.8) with irregular genital bleeding were
      investigate. Using transvaginal ultrasound, anterior-posterior, length and width
      dimensions of the uterus were measured and echostructure of the endometrium was
      defined. The dilatation and curettage of endometrial cavity was performed
      subsequently. RESULTS AND DISCUSSION: The histological examination of the
      curettage material shows - normal endometrium in 15 women, cystic hyperplasian in
      16, atrophic endometrium in 11, atypical hyperplasia in 5 and endometrial cancer
      in 3 women. The correlation of these findings with the results from ultrasound
      investigation shows, that the degree of the endometrial thickness play a role as
      a criteria to establish the diagnostic protocol. CONCLUSION: The summarized data
      from our study shows, that in the limit of 8 mm, the diagnostic accuracy of the
      method - sensitivity - 75% specificity - 73.8% amd efficacy - 74% give us cause
      to recommend the transvaginal sonography of the endometrium in women in climax,
      as a screening tool in the diagnostic protocol for endometrial cancer.

PMID- 11519303
TI  - [Early oral intake after cesarean section and gynecological operations].
AB  - The authors present a modern review on the early oral intake after cesarean
      section and gynecological operations and their own experience with 130 cesarean
      and 100 gynecological operated women. This is for the first time on our
      (Bulgarian) practice. Early oral intake was well tolerated by the patients, there
      were no more postoperative complications associated with the new method of
      postoperative care. The authors recommended this approach for the clinical
      practice.

PMID- 11519304
TI  - [Effects of ionizing radiation on the embryo and fetus].
AB  - The developing embryo and fetus are extremely sensitive to ionizing radiation.
      The main effects of radiation on he human embryo and fetus are: growth
      retardation, prenatal or neonatal death, congenital malformations and mental
      retardation. The incidence of these radiation effects at different stages of
      gestation, the relations with absorbed doses and threshold doses are discussed.
      Epidemiological data that reveal high susceptibility to carcinogenic effects of
      radiation during in utero life are presented. A dose of 0.1 Gy (10 rad) to the
      embryo and fetus is recommended as a threshold dose, above which a therapeutic
      abortion should be considered. Diagnostic radiation exposures will reach this
      level in a very rare cases. The threshold dose, which is an indication for
      pregnancy termination must be flexible, in a large tolerance, depending on other
      possible risks of the pregnancy as well as the personality of the future parents.

PMID- 11519305
TI  - [Postmenopausal and posthysterectomy osteoporosis. December 1,2000].

PMID- 11519306
TI  - [The management of reproductive health programs: experience, achievements,
      goals].

PMID- 11519307
TI  - [Preimplantation genetic diagnosis: current status and perspective].
AB  - Scientific and clinical aspects of preimplantation genetic are represented.

PMID- 11519308
TI  - [Large uterine myoma during pregnancy and delivery - choice of management].
AB  - There are scanty of available data about the management of myoma of the uterus
      during pregnancy and birth. The authors describe two cases of such a pathology-
      big myoma of the uterus > 10 sm diameter (d.), who were treated conservatively
      and ended successfully, without serious complications. The pregnant women were
      done cesarean section and during the operation the myomas were excisiert. There
      were no complications intra- and postoperationem. The authors suggest that
      myectomy during pregnancy and cesarean section must not be don routinely.

PMID- 11519309
TI  - [Glassy cell carcinoma - a rare variant of cervical carcinoma].

PMID- 11519310
TI  - [Endometrial carcinoma in a 25-year-old woman found incidentally in a routine
      examination for infertility].

PMID- 11519312
TI  - [Subdermal implantation of estradiol 17 beta (25 mg) in hysterectomized and
      ovariectomized women. Effects of increased serum estradiol level and
      neurovegetative climacteric complaints].

PMID- 11519311
TI  - [Modern treatment of vaginal mycosis in adolescence].
AB  - The aim of the study is to determine the effectiveness of the single per oral
      application of 200 mg Fungolon (Fluconazolum) in adolescent girls with proven
      Candida spp. Vaginal infection. MATERIAL AND METHODS: A prospective, case control
      study in 50 girls, aged 9 to 18 years, was performed. Patients were recruited in
      the outpatient Clinic of Paediatric and Adolescent Gynecology at the University
      Hospital "Majchin dom", Sofia, Bulgaria. They suffered from vaginal discharge
      and/or pruritus of the external genitalia. Candida spp. Was proven in all of the
      microbiological investigation performed. The treatment with Fungolon was
      performed per os, in single dose of 200 mg. RESULTS: The complaints and Candida
      in the vaginal smear (controlled 1 week after the treatment) disappeared in 43 of
      50 patients (86%) treated. No effect was observed in 7 girls (14%). A reinfection
      with Candida was observed in 6 of the 38 patients (16%) at the second week after
      the treatment. The typisation of the resistant to Fungolon Candida shown
      predominance of Candida glabrata. There were no side effects registered during
      the Fungolon treatment. CONCLUSION: The treatment of Candida spp. Vaginal
      infection in adolescent girls by a single per oral application of 200 mg Fungolon
      (Fluconazolum) is very convenient and efficient. It gives a prompt effect (the
      complaints disappear in one or two days), high percentage of healed patients
      (86%), with absence of side effects. The usage of Fungolon should be highly
      recommended for treatment of vaginal mycoses in puberty and adolescence.

PMID- 11519313
TI  - [Remifemin - an alternative to hormone replacement therapy in the climacteric
      syndrome].

PMID- 11519314
TI  - [Prophylaxis with Tercef of infection-related complications following cesarean
      section].

PMID- 11519315
TI  - [Inflammatory disease of the pelvis].

PMID- 11519316
TI  - [Treatment of mycotic vaginitis with Fungolon].

PMID- 11519317
TI  - [Clinical study of low-dose oral contraceptives (with low-doses of ethinyl
      estradiol), widely used in practice].

PMID- 11519318
TI  - [Patentex Oval - a modern local contraceptive].

PMID- 11519319
TI  - [Hysteroscopic diagnosis of endometrial carcinoma].
AB  - Searching of more effective methods for early diagnosis of Endometrial Cancer has
      confirmed the hysteroscopy as most complete and sufficient manner in this
      direction. In the present exposition the authors are sharing their experience and
      making some practical conclusions that may be useful for the physicians applying
      this method.

PMID- 11519320
TI  - [Treatment of genital chlamydia infections with Sumamed].

PMID- 11519321
TI  - [Hereditary ovarian cancer].

PMID- 11519322
TI  - [Lipoleiomyoma of the uterus].

PMID- 11519323
TI  - [Surgery for uterine myoma].
AB  - The authors present one supervision of surgically activity and myoma of the
      uterus in the period 1995-2000 year. 456 women with myoma are surgical treatment;
      by 319 are perform LHT cum and., by 63-LHT sine and., by 37 myomectomia and by 37
      LHT sine and dex/sin.

PMID- 11519324
TI  - [Biochemical changes in senile cataract].
AB  - Oxidative mechanism may play an important role in maturity onset cataract. But,
      nowadays, there is no answer whether cataract is the result of oxidation per se
      or of exaggerated and inappropriate physiological responses to oxidation. Also,
      senile cataract may be considered a conformational disease. Understanding the
      mechanisms of cataractogenesis will lead to a better therapy.

PMID- 11519325
TI  - [Posttraumatic posterior lens luxation].
AB  - This paper presents a few theoretical considerations about the posttraumatic
      posterior luxation of the nucleus. We discuss the evolution and surgical
      treatment of a clinical case, and we remark once more that the posterior luxation
      of the nucleus is considered to be an delayed surgical emergency.

PMID- 11519326
TI  - [Bourneville tuberous sclerosis].
AB  - The article shows a case of Bourneville's disease, a quite rare neuroectodermal
      phacomatosis. We show how we establish the diagnosis, beginning with a total
      unspecifical symptomatology.

PMID- 11519327
TI  - [Left temporal arachnoid cyst].
AB  - Ocular onset is seldom for an arachnoid cyst. We present the case of a young man
      whose only symptom when hospitalized, was the unilateral peripheral field
      contraction. It was afterwards specified the presence of the arachnoid cyst and
      it's pathogenic feature, the compression of the optic nerve.

PMID- 11519328
TI  - [Conjunctival intraepithelial carcinoma, recurrent after surgical excision--case
      report].
AB  - The malignant epithelial tumors of the sclerocorneal limbus are rare. The paper
      reports a case of an intraepithelial carcinoma, operated and relapsed, the
      therapeutics solution and the postsurgery evolution after six months.

PMID- 11519329
TI  - [Again "about residency " or more exactly "about professional education"].

PMID- 11519330
TI  - [Ophthalmologic involvement of intracranial tumors--report of a case].
AB  - Bilateral papillary edema is considered to be the expression of a tumoral process
      that reduces the intracranial space resulting in elevation of the intracranial
      cerebrospinal fluid pressure. The authors present the case of a 21-year-old man
      consulting for mild visual loss of the left eye. The ophthalmologic examination
      showed bilateral papilledema and visual field defects in the left eye
      (enlargement of the blind spot), with no clinic or imagistic signs of increased
      intracranial pressure. Intracranial pathologic processes that bear like a tumor,
      reducing the intracranial space are not always associated with papilledema, but
      papilledema is always associated with intracranial tumor. Increased intracranial
      pressure is frequently associated with intracranial tumoral processes, but in
      this case was not showed increasing of intracranial pressure.

PMID- 11519331
TI  - [Ocular cysticercosis - case report].
AB  - This paper presents a particularly case regarding ophthalmic cysticercosis. It
      was necessary the association of clinical dates with the paraclinical
      investigations (echography, immunological tests) to degree the diagnosis.

PMID- 11519332
TI  - [Myopic peripheral retinal degenerations].
AB  - The article shows periferical retinal degenerations which appear in myopia. The
      places, the ophthalmoscopical aspect and histopathological aspect of each retinal
      change and the complications that may appear are presented. In the end some
      principles of treatment are presented.

PMID- 11519333
TI  - [Penetrating ocular trauma--therapeutic approach].
AB  - The most important factor for functional and anatomic prognosis of an injured eye
      is the appropriate emergency assistance. This paper presents a case of
      penetrating ocular trauma with minor clinical sings which associates severe
      lesions of posterior pole discovered intraoperatively. Careful history and
      clinical examination allowed the best surgical management, with complete
      anatomical and functional recovery of the eye.

PMID- 11519334
TI  - [Uveitic cataract surgery].

PMID- 11519335
TI  - [Laser phacoemulsification--a method of cataract surgery].
AB  - Today, ultrasound phacoemulsification is the most used method of cataract
      surgery. Because the side effects (injury of corneal endothelium and other nearly
      tissues), was tried to find alternative energy forms. Erbium laser was proven to
      be the most effective method among all of these.

PMID- 11519336
TI  - [Corticosteroids in ophthalmology].
AB  - Within ophthalmology there are many indications for the use of corticosteroids,
      but the decision to institute steroid therapy always requires careful
      considerations of the relative risks and benefits in each patient. This review
      considers the mechanisms of action, the ocular and non-ocular problems
      encountered when steroids are used, with practical suggestions to minimise their
      side effects and the therapeutic options for clinical use.

PMID- 11519337
TI  - [The importance of AFG in diagnosis and therapeutic indication in retinal vein
      branch occlusion].
AB  - In the beginning the paper presents some concepts needed to understand the
      pathological and the angiographic aspects of the branch retinal vein occlusion.
      In the second part we outline based on exemplification from the authors cases the
      indications and the relevance of the fluorescein angiography in the branch
      retinal veins occlusion and theirs complications.

PMID- 11519338
TI  - [Dry eye-blepharoconjunctivitis relationship].

PMID- 11519339
TI  - [Less frequent etiology in uveitis].
AB  - This material intends to present three clinical observations regarding the
      uveitis etiology, that is represented by the association of some etiological
      factors less known: Toxoplasma gondii, Listeria monocytogenes, Leptospira
      icterohaemorrhagiae. The uveitis described here have been severe in the fast
      evolution and with trends of reappearence. This work demonstrates that the strict
      etiological antibacteria and antiparasite therapy is not enough and only
      corticotherapy is able to fight against the accentuated inflammatory phenomena
      that go along with type of uveitis.

PMID- 11519340
TI  - [Tears' immunology in acute eye diseases].
AB  - The aim of the study is to research the immunoglobulins' concentration into the
      tears liquid and into the blood serum at the patients with acute affections of
      the anterior ocular pole. The study was accomplished on two groups of patients:
      one group with herpetic Keratitis, the other with anterior uveitis, the second
      having a different etiology--that the viral one. Another group of patients with
      senile cataract was used like witness-group. The immunoglobulins concentration
      were detected into the serum and into the tears by the Mancini method of the
      radial immunodiffusion. The results indicate a general immunodefficiency signed
      by the decrease of IgG and IgM into the serum on the one hand, and the increase
      of local defense mechanisms reflected on the growing of IgA and IgG level into
      the tears, on the other hand.

PMID- 11519341
TI  - [Physiopathology in accommodation and presbyopia, clinical and surgical
      approach].
AB  - Accommodation is a complex of phenomena by which the refracting power of the eye
      changes for focusing on near vision. Accommodative amplitude declines
      progressively with increasing age. Until today, this phenomenon called presbyopia
      was explained by Helmholtz's hypothezis which involves only ciliary muscle. It
      seems that in accommodation are involved, besides the ciliary muscle, the lens
      and extraventicular elastic components, biophysical dynamics of the lens capsule,
      vitreous, iris. According with the role of these factors and theirs
      pathophysiological implications, new surgical technique has developed to reverse
      presbyopia in the human eye (Surgical reversal presbyopia, Anterior ciliary
      sclerotomy) and offers a potential for understanding ocular hypertension and
      treatment of primary open-angle glaucoma.

PMID- 11519342
TI  - [Prevalence of glaucoma suspect in patients with central vein occlusion].
AB  - PURPOSE: To prospectively study in a 10 year follow-up period the dynamics of the
      prevalence of the glaucoma suspect in patients with central retinal vein
      occlusion. METHODS: The study group consisted of 147 patients without diabetes
      who sustained a unilateral occlusion of the central retinal vein not treated by
      pan-retinal photocoagulation. As control group 100 age-matched patients belonging
      to the general population without central retinal vein occlusion and diabetes
      were used. RESULTS: From an initial frequency of 10.8% the prevalence of the
      glaucoma suspect had a progressive elevation that hit the highest value of 20.4%
      in the 5 month following the onset of the occlusion. The decrease of the
      prevalence down to 4.7% by the end of the follow-up period was accounted for by
      the fact that in 9 cases a neovascular glaucoma occurred, in 6 cases the central
      retinal vein occlusion accompanied by glaucoma suspect developed toward an
      occlusion with normal intraocular pressure and in 8 patients the glaucoma suspect
      converted into a primary open-angle glaucoma. The prevalence of the glaucoma
      suspect in patients of the control group was low, ranging between 1 and 4%.
      CONCLUSIONS: The central retinal vein occlusion influences the onset as well as
      the development of glaucoma suspect. Glaucoma suspect associated with the central
      retinal vein occlusion represents a risk factor for the occurrence of both the
      neovascular glaucoma and the primary open angle glaucoma.

PMID- 11519343
TI  - [Fluorescein angiography diagnosis in Stargardt disease].
AB  - The paper present in the first part some general data on Stargardt and its
      diagnosis. In the second part we present a case showing the importance of the
      angiographic aspect in establishing the diagnostic.

PMID- 11519344
TI  - Save time and apply for survey online.

PMID- 11519345
TI  - Exposure to Creutzfeldt-Jakob disease.

PMID- 11519346
TI  - Disease-specific care program under construction.

PMID- 11519347
TI  - Establishing a single-source approach to measuring quality.

PMID- 11519348
TI  - Resolving type Is in a written progress report.

PMID- 11519349
TI  - Linking staffing and quality issues.

PMID- 11519350
TI  - An ultrastructural study of the Antarctic calanoid Copepod Metridia gerlachei
      giesbrecht, 1902. Adult female.
AB  - Scanning electron microscopy (SEM) techniques can highly contribute to the
      knowledge of body structures in order to differentiate between different species
      or between varieties within the same species.  This is particularly important in
      extreme environments, such as in Antarctic waters, where the evolution efforts
      have promoted the development of endemisms.  In this work the external anatomy of
      Metridia gerlachei (Copepoda, Calanida) adult females, sampled during the Italian
      Oceanographic Campaign in Antarctica 1987-88, was described by SEM, particularly
      considering some swimming legs and the genital abdominal joint.  The descriptions
      already reported have been verified and some morphological details have been
      better emphasized.  As concerns the P2, the hook process of the first segment of
      endopod and a series of spines vaguely indicated, but not defined, in previous
      descriptions have been clearly evidenced.  In the P5 the occurrence of three well
      separated free segments and the location of a marginal sets have been shown.  The
      ultrastracture of the genital segment showed that a clear areola surrounds the
      genital field.

PMID- 11519351
TI  - Heat Shock Protein 27 is overexpressed in the skin of bitumen exposed workers.
      Early observations.
AB  - The skin of road pavers is exposed to a large number of compounds such as
      asphalt, bitumen, amines, polymers, oils, solvents, sand, gravel, crushed rock,
      mineral wad, ultraviolet light and heat.  In order to verify an up-regulation of
      HSP27, determined by the above mentioned stimuli, we studied,
      immunohistochemically, the forearm skin of a sample of road pavers occupationally
      exposed.  A total of 25 punch biopsies (3 mm  diameters) was obtained from the
      foream skin of road paver workers (n=16) and a control group (n=5) not exposed. 
      Specimens were sectioned (thickness: 3-4 micron   ) and processed for
      immunohistochemistry.  For localization of HSP27, a mouse anti-HSP27 monoclonal
      antibody was used.  In punch biopsies of bitumen exposed workers, HSP27
      immunostaining was hemogeneously detected in the whole epidermis including basal
      cell layer. Immunoreaction products were observed mostly in cytoplasm but also in
      nuclei.  Staining intensity was stronger (grade 3 or 4) than that revealed in
      normal skin sample.

PMID- 11519352
TI  - [Nitric oxide as main effector in the interleukin-1 system in ovulation].
AB  - Ovulation is a complex process involving not only gonadotropins and steroid
      hormones, but also many local mediators common to inflammatory reactions, such as
      cytokines. Of particular interest is the ovarian interleukin-1 (IL-1) system,
      which may be an intermediary of gonadotropins in the ovulatory process. The
      preovulatory follicles have a complete and highly compartmentalized intraovarian
      IL-1 system including ligands, receptor, and receptor antagonist. IL-1 has been
      considered as the inductor of several ovulation-associated events such as
      prostaglandin and progesterone biosynthesis, plasminogen activator production,
      glycosaminoglycan generation, and enhancement of vascular permeability. The
      principal effector of the IL-1 system is nitric oxide. This paper analyzes the
      sites of synthesis and action of the IL-1 system in preovulatory follicle and its
      vascular dynamics as well as IL-1's mechanism of action in triggering follicular
      rupture.

PMID- 11519353
TI  - [Risk factors for peptic ulcer recurrence].
AB  - Prevalence of peptic ulcer (PU) and risk factors associated with its recurrence
      are unknown among the Mexican population. OBJECTIVE: To determine clinical
      features and risk factors associated with peptic ulcer recurrence. MATERIAL AND
      METHODS: Five-year follow-up study that included 211 men and 140 women 20 years
      age or older. PU diagnosis was made by clinical and endoscopic criteria.
      Associated risk factors such as NSAIDs use, smoking, alcohol consumption, and H.
      pylori infection were assessed. Clinical recurrence was defined as the time
      between basal diagnosis and the first PU clinical drop. RESULTS: Diagnosis of
      duodenal ulcer (DU) and gastric ulcer (GU) was documented in 41.9 and 58.1% of
      subjects. Predominant risk factor for DU was smoking, and NSAID intake for GU. H.
      pylori were documented in 39.3%. Sixty-five years of age or older (61 and 33% for
      GU and DU, respectively), and three or more associated risk factors (70%) were
      the main associated causes for PU recurrence. PU recurrence associated with Hp
      was 34%. CONCLUSIONS: GU frequency was the highest and associated risk factors
      for its recurrence were NSAID intake, 65 years of age or older, and Hp infection.

PMID- 11519354
TI  - [Antiinflammatory effect of a topical corticosteroid: known brand versus generic
      drug].
AB  - In Mexico, the generic drug market is growing. Regarding topical corticosteroids,
      there are several preparations on the local market but their clinical efficacy
      has not been assessed in relation with the original brand name. Using as a model
      the fluocinolone acetonide cream, the purpose of this study was to evaluate the
      antiinflammatory effect of different preparations. A double-blind, vehicle
      control essay was conducted causing irritation on five sites of the volar aspect
      of the forearm in twenty healthy volunteers using 10% aqueous sodium lauryl
      sulfate. On the same part of the forearm, the formulations tested were applied
      for a period of 4 days with visual score irritation readings at days 2 and 4. The
      analysis of the results showed that although one of the generic drugs is 80% less
      expensive than the brandname medication, the clinical response was not as good as
      the other preparations. This deserves consideration, as newer and more potent
      generic corticosteroids will be available on the Mexican market.

PMID- 11519355
TI  - [Factors that influence non-donation of blood in relatives of patients at a
      pediatric hospital].
AB  - OBJECTIVE: To identify factors that influence refusing to donating blood.
      MATERIAL AND METHODS: Prospective case and control study. Hospitalized patients'
      relatives were interviewed with a questionnaire to evaluate their knowledge of
      blood and personal attitudes toward blood donation. Cases were all relatives who
      did not donate blood and controls who did. RESULTS: A total of 121 individuals
      was studied, 30 cases and 91 controls. Age of the cases was 32.3 +/- 8.1 years
      and controls was 28.8 +/- 7.9 years (p = 0.04). Risk factors were female sex (OR
      = 6.3; 95%CI 2.4 to 17.1), being married (OR = 3.7 95%CI 1.3 to 10.5). No
      differences were present between the two groups in level of knowledge concerning
      blood. The average of positive attitudes toward blood donation was greater among
      relatives who donated blood (cases 5.9 +/- 1.6; controls 6.4 +/- 1.2; P = 0.049).
      Among the attitudes that influence refusing to donate blood were fear of getting
      dizzy at the sight of blood (OR = 5.2, 95%CI 1.3-21.4), fear of donating blood
      (OR = 2.2, 95%C, 0.8-6.0), and getting nervous at the sight of blood (OR = 4.1,
      95%CI% 1.5-10.9). CONCLUSIONS: Among patient's relatives who donate blood
      positive personal attitudes toward blood donation have more weight than knowledge
      on the subject.

PMID- 11519356
TI  - [Obesity in the 21st century. Progress in etiopathogenesis and treatment].
AB  - Obesity is complex in its etiology and treatment. Its global incidence is
      increasing significantly. Favoring weight-loss can only bring beneficial effects.
      Obesity is a chronic condition with multifactorial origin. The discovery of the
      ob gene and its product, the OB protein or Leptin, neuropeptide Y, and the
      alterations of the metabolism of lipogenic tissues that inhibit appetite are
      significant advances in the understanding of its etiopathogenesis and treatment.
      This new knowledge will change the philosophy of the management of obesity.
      Obesity responds poorly to nonsurgical therapies. Its treatment must be long-term
      in spite of the considerable social and biological pressure that favor the
      regaining of weight. Treatment of the obese patient must be performed by a
      multidisciplinary team, and should include a hypoenergetic diet, exercise
      program, behavioral modifications, and in some instances, family therapy. The
      treatment of obesity should be tailored for each individual. Drug use in the
      treatment of obesity is not a substitute for modifying the individual's diet and
      physical activity. Bariatric surgery is indicated only when the BMI is greater
      than 30 kg/m2. Physicians and patients must interact closely and assess possible
      risks that are involved in its treatment against real benefits. A good relation
      between practitioner and patient is essential.

PMID- 11519357
TI  - [Hyperhomocysteinemia. A new coronary risk factor].
AB  - Cardiovascular disease is the leading cause of mortality in Mexico, as well as in
      other Western countries. Conventional risk factors for atherosclerosis, such as
      cigarette smoking, systemic hypertension, diabetes mellitus, and
      hypercholesterolemia, do not explain this association completely. Recently, it
      has been recognized that hyperhomocysteinemia contributes to the atherosclerotic
      process, promoting endothelial damage and oxidative stress in the vascular wall.
      Homocysteine, an amino acid generated under physiologic conditions after
      ingestion of protein-rich foods, is used in a variety of metabolic pathways.
      Elevated plasma levels of this amino acid (higher than 15 mmol/L or lower in the
      presence of other cardiovascular risk factors) promote the development of
      atherosclerosis. Folic acid and vitamin B6 and B12 supplements decrease plasma
      levels of homocysteine effectively and may play an important role in the
      prevention and treatment of atherosclerotic vascular disease.

PMID- 11519358
TI  - [Young infant with febrile syndrome, acute progressive encephalopathy and hepatic
      functional alteration].

PMID- 11519359
TI  - [Type B right ventricle thrombus in transit].

PMID- 11519360
TI  - [Cranial metastasis of thyroid follicular carcinoma. Report of a case].
AB  - Thyroid follicular carcinoma is able to produce metastatic lesions before the
      vanishing of the primary lesion. We present a case of a woman with a lytic,
      solitary, asymptomatic parietal bone lesion of 2 years of evolution. Autopsy
      revealed a thyroid gland with two small cystic areas and renal metastasis.
      Thyroid carcinoma should be included in the differential diagnosis in cases of
      lytic bone lesions with long evolution in patients 60 years of age or older.

PMID- 11519361
TI  - [Physicians facing the first antituberculosis campaign in Mexico].
AB  - In the paper entitled "Physicians Face the First Antituberculosis Campaign in
      Mexico", tuberculosis is focused on as an important cause of death and disability
      in many parts of Mexico in the last quarter of the ninetieth century and the
      first decade of the twentieth century. The first measures taken are described,
      along with the formal proposal that attempted to include institutions as well as
      individuals. The manner in which tuberculosis was associated with nutrition, with
      alcoholism and with work and life conditions is studied. As a last point, the
      debate among medical professionals that was provoked by the campaign against
      tuberculosis is analyzed.

PMID- 11519362
TI  - [Plagiocephaly].

PMID- 11519363
TI  - [The first molecular marker in glaucoma].

PMID- 11519364
TI  - [Bioethics and scientific training of physicians].
AB  - Bioethics is becoming a major current in modern medical thought and action. Given
      the youth of this field of enquiry, there are still important debates and
      controversies on its proper role in medicine and in medical education, but the
      need to foster its integral incorporation into the formative process of the
      physician is unreservedly accepted, on an equal footing with the scientific,
      technical, and humanistic components of medical training.

PMID- 11519365
TI  - [The Helsinki Declaration of the World Medical Association].

PMID- 11519366
TI  - [The insurance institutions specialized in health in Mexico].

PMID- 11519367
TI  - Voices from the field: providers discuss HIV counseling and testing programs for
      drug users.
AB  - The use of illicit drugs plays a critical role in the spread of HIV, with
      approximately one-half of all new HIV infections in the United States attributed
      to this mode of transmission. There is a renewed emphasis on developing special
      HIV counseling and testing (C&T) programs for drug users. We conducted a
      qualitative study of C&T providers to identify client-centered and structural
      barriers to providing HIV C&T to high-risk drug users. Interviews focused on
      obtaining a detailed description of the services; successful and problematic
      forms of organization, financing, and service delivery; client access and
      barriers to C&T services; recommendations for increasing C&T accessibility and
      utilization by drug users; and linkages between C&T and other HIV-prevention and
      intervention services. The results of our interviews illustrate that it is
      tremendously complex and challenging work to provide C&T to populations with
      multiple and immediate needs within a context of layered constraints on
      individual behavior, provider resources, and service delivery. Providers clearly
      understand client-centered and structural barriers and have demonstrated a
      commitment to overcoming the barriers related to AIDS stigma, confidentiality,
      material needs, and fear when delivering HIV C&T services.

PMID- 11519368
TI  - Expanding access to early HIV care: new challenges for federal health policy.
AB  - Advances in biomedical research have resulted in new standards for HIV treatment
      that involve earlier intervention with more complex combination antiretroviral
      therapy. This article examines the implications of these treatments for federally
      funded programs that provide HIV care and discusses mechanisms for making
      Medicaid and the AIDS Drug Assistance Program (ADAP) consistent with the
      treatment standards. The article provides a rationale for expanding access by
      expanding entitlement programs (Medicaid) rather than discretionary programs
      (ADAP). A potential legislative approach to Medicaid expansion is described. Cost
      projections suggest that this approach is feasible and would constitute a
      significant step toward increasing access to HIV care.

PMID- 11519369
TI  - HIV prevention community planning and communities of color: do resources track
      the epidemic?
AB  - The Centers for Disease Control and Prevention (CDC) funds provided to state,
      local, and territorial health departments for HIV-prevention activities are
      prioritized with the substantial involvement of HIV-prevention community planning
      groups (CPGs). This article examines whether or not these funds (more than $261
      million in fiscal year 1998) are allocated in a way that mirrors the HIV/AIDS
      epidemic in terms of race/ethnicity. AIDS prevalence data were used to reflect
      disease burden, and were compared to budget data submitted by health departments
      to the CDC. The budget data report expenditures by race/ethnicity for two major
      types of activities: (1) health education and risk reduction (more than $104
      million); and (2) counseling, testing, referral, and partner notification (more
      than $91 million). The rank order correlation between funding and AIDS prevalence
      data for the five specific racial/ethnic categories was .900 (n = 5, p < .05) for
      health education and risk reduction (HERR) activities, and 1.000 (n = 5, p < .05)
      for counseling, testing, referral, and partner notification (CTRPN) activities.
      From 1997 to 1998, the proportion of funds targeted and accounted for by
      race/ethnicity increased from 79 percent to 88 percent for HERR, and from 71
      percent to 84 percent for CTRPN activities. With regard to race/ethnicity, health
      departments and CPGs appear to be actively targeting and accounting for HIV
      prevention resources, and we will argue that relatively small changes in
      counseling and testing resources for African-American and Latino/Latina
      communities would result in a close match between AIDS prevalence data and
      devoted resources.

PMID- 11519370
TI  - Medical malpractice as a basis for a false claims action?

PMID- 11519371
TI  - Drug abuse prevention among minority adolescents: posttest and one-year follow-up
      of a school-based preventive intervention.
AB  - Most drug abuse prevention research has been conducted with predominantly White
      middle-class adolescent populations. The present study tested a school-based drug
      abuse preventive intervention in a sample of predominantly minority students (N =
      3,621) in 29 New York City schools. The prevention program taught drug refusal
      skills, antidrug norms, personal self-management skills, and general social
      skills in an effort to provide students with skills and information for resisting
      drug offers, to decrease motivations to use drugs, and decrease vulnerability to
      drug use social influences. Results indicated that those who received the program
      (n = 2,144) reported less smoking, drinking, drunkenness, inhalant use, and
      polydrug use relative to controls (n = 1,477). The program also had a direct
      positive effect on several cognitive, attitudinal, and personality variables
      believed to play a role in adolescent substance use. Mediational analyses showed
      that prevention effects on some drug use outcomes were mediated in part by risk
      taking, behavioral intentions, and peer normative expectations regarding drug
      use. The findings from this study show that a drug abuse prevention program
      originally designed for White middle-class adolescent populations is effective in
      a sample of minority, economically disadvantaged, inner-city adolescents.

PMID- 11519372
TI  - Mediating mechanisms in a program to reduce intentions to use anabolic steroids
      and improve exercise self-efficacy and dietary behavior.
AB  - This study investigated the mediating mechanisms responsible for the effects of a
      program designed to reduce intentions to use anabolic steroids, improve
      nutrition, and increase strength training self-efficacy. Fifteen of 31 high
      school football teams (N = 1,506 players at baseline) in Oregon and Washington
      were assigned to receive the intervention. The multicomponent program addressed
      the social influences promoting ergogenic drug use and engaging students in
      healthy nutrition and strength training alternative behaviors. Although the
      results differed across the three dependent variables, the program appeared to
      work by changing team norms. Unlike prevention of other drugs, changes in
      knowledge and perceived severity were mediators of program effects in this study.

PMID- 11519373
TI  - Are risk and protective factors for substance use consistent across historical
      time?: national data from the high school classes of 1976 through 1997.
AB  - Researchers have seldom examined whether risk and protective factors are
      consistently linked to substance use across historical time. Using nationally
      representative data collected from 22 consecutive cohorts of high school seniors
      (approximate N = 188,000) from the Monitoring the Future (MTF) project, we
      investigated whether correlates of substance use changed across historical time.
      We found a high degree of consistency across historical time in predictors of
      past month cigarette use, past month alcohol use, past year marijuana use, and
      past year cocaine use. Some predictors such as religiosity, political beliefs,
      truancy, and frequent evenings out were consistently linked to substance use. The
      consistency of other predictors such as region, parental education, and college
      plans was contingent in part upon historical time period, the particular
      substance, and its level of use.

PMID- 11519374
TI  - Applying cost analysis methods to school-based prevention programs.
AB  - In order to efficiently allocate scarce prevention resources, policymakers need
      information about the economic costs of school-based substance use prevention
      programs. The objective of this paper is to outline economic cost analysis
      methods and demonstrate their applicability to school-based prevention programs.
      As an example, the paper focuses on estimating the economic cost of ALPHA, an
      intensive school-based substance use prevention program. The cost of ALPHA is
      compared to the costs of 3 elementary school programs that were alternatives to
      ALPHA. We collected cost information for 3 years, using a cost questionnaire that
      was completed by program and school budget officers and school principals. The
      program costs obtained from these sources were modified to conform to well
      established economic cost analysis principles.

PMID- 11519375
TI  - Etiology and prevention of substance use among Asian American youth.
AB  - Among populations identified by the U.S. Bureau of the Census, it is anticipated
      that the Asian/Pacific Islander (API) population will experience the greatest
      change between 1990 and 2050 (U.S. Bureau of the Census. [1996, February].
      Current population reports. Series P25-1130. Washington, DC: U.S. Government
      printing office). Limited studies focus on APIs as a racial group and still fewer
      disaggregate samples to specific ethnic Asian subgroupings. This paper begins
      with definitions of the API communities, then examines rates of adolescent drug
      use, risk and protective factors, and preventive intervention effectiveness
      focused on API communities. The limited epidemiological data suggest that in
      general, APIs are at a relatively lower risk for drug use than youth from most
      other ethnic groups. However, the available data also suggest that use may not be
      as low as generally assumed with rates for alcohol use, smoking, and some illicit
      drugs being equal to or exceeding those of African Americans and European
      Americans. Despite the paucity of available data on particular Asian subgroups,
      the available data demonstrate that there are differences among API subgroups,
      underscoring the importance of identifying Asian subgroups when studying
      substance use and when planning prevention and treatment. The limited data
      examining the etiology of drug use across API subgroups suggests that some of the
      risk and protective factors derived from majority based research may also be
      predictors for these populations. These data support the utility of examining the
      generalizability of existing tested prevention approaches among different API
      communities. Finally, further efforts should be made to encourage and support the
      evaluation of community-based programs that already target and deliver services
      to API youth.

PMID- 11519376
TI  - A gene causing autosomal recessive cataract maps to the short arm of chromosome
      3.
AB  - BACKGROUND: Fourteen loci have been associated with autosomal dominant cataract,
      but only one with the recessive form of the disease. OBJECTIVES: To find the
      chromosomal location of a gene causing autosomal recessive cataract in three
      inbred Arab families. METHODS: A single nucleotide polymorphism-based genome-wide
      search, with the Effvmetrix GeneChip HuSNP genotyping array, was performed on a
      pooled DNA sample from six affected family members in a search for regions
      showing homozygosity. Using conventional microsatellite markers, regions of
      homozygosity were further analyzed in all the families. RESULTS: A region on
      chromosome 3p spanning 43 megabases showed homozygosity with 13 consecutive SNPs.
      Three microsatellite markers from this region yielded lod scores > 3.00. A
      maximal two-point lod of 4.83 was obtained with the marker D3S1298 at theta =
      0.004. Haplotype analysis placed the disease gene in a 20 Mb interval between
      D3S1768 and D3S2409. CONCLUSIONS: A gene causing autosomal recessive cataract
      maps to the short arm of chromosome 3.

PMID- 11519377
TI  - Extensive necrosis in renal cell carcinoma specimens: potential clinical and
      prognostic implications.
AB  - BACKGROUND: Extensive necrosis is rare in primary renal cell carcinoma. This
      finding may reflect the biological characteristics of the carcinoma and therefore
      could be of prognostic and clinical value. OBJECTIVES: To assess the incidence of
      necrosis in renal cell carcinoma and its potential prognostic value. METHODS: We
      conducted a consecutive retrospective study of 173 patients after radical
      nephrectomy for renal cell carcinoma. Clinical and pathological data were
      collected from hospital medical records and compiled into a computerized
      database. RESULTS: Extensive necrosis was found in 31 tumor specimens (17.9%).
      Univariate analysis showed that the specimens with extensive necrosis were
      significantly larger and manifested more perirenal and venous extension than the
      tumors without necrosis. The size of the renal tumor was the only parameter that
      remained significant in multivariate analysis (P = 0.0001). Overall disease-free
      survival did not differ significantly between patients with necrotic tumors and
      those without (68% and 66% respectively). CONCLUSIONS: The finding of extensive
      necrosis in renal cell carcinoma specimens does not seem to be related to tumor
      biology but rather may reflect the relation between size and vascularity of the
      tumor.

PMID- 11519378
TI  - Effect of electrocautery vs. scalpel on fascial mechanical properties after
      midline laparotomy incision in rats.
AB  - BACKGROUND: The method of midline laparotomy incision and closure remains a
      complex surgical problem. OBJECTIVE: To compare the mechanical properties at the
      interface of midline laparotomy incision made by scalpel versus electrocuting
      current in rats. METHODS: A sharp midline laparotomy incision was made in 60
      Wistar female rats using a scalpel or electrocautery to open the fascia. The
      fascial and skin wounds were closed separately with a continuous nylon. Fascial
      specimens were analyzed for mechanical properties at the midline incision using a
      loading machine. The load-extension curve was recorded during tensile loading at
      a steady extension rate of 15 mm/min. RESULTS: There was no statistically
      significant difference between the two groups in either wound-bursting force
      (PPEAK) or the strain energy spent until the point of measured PPEAK. Each load
      extension curve showed a characteristic pattern in all rats. Tissue stiffness was
      greater in the scalpel group than in the electrocautery group (P = 0.02).
      Correlations were found between tissue stiffness and strain energy, between
      tissue stiffness and bursting force, and between bursting force and strain
      energy. CONCLUSIONS: While tissue stiffness was greater when a scalpel was used
      compared to electrocuting to incise the midline abdominal fascia in rats, there
      was no difference in the bursting force required to disrupt the wound.

PMID- 11519379
TI  - Assessment of work-related risks factors for carpal tunnel syndrome.
AB  - BACKGROUND: The association of carpal tunnel syndrome with occupational risk
      factors is well established. However, in clinical practice these factors are only
      rarely considered and evaluated. Managing these risk factors could prevent the
      occurrence of future cases and alleviate treatment of the afflicted individuals.
      OBJECTIVES: To estimate the role of occupational risk factors in a large group of
      patients diagnosed by electrophysiological studies as suffering from CTS.
      METHODS: A group of 396 subjects (204 women, 165 men) who were tested in one
      laboratory by electrophysiological studies were further evaluated (by
      questionnaire) to determine the possible role of occupational and other risk
      factors in the etiology of their syndrome. RESULTS: Persons employed in high
      force--low repetitive or low force--high repetitive jobs, harbor an extra risk
      for developing CTS as compared with controls, OR = 3.21 (95% C1 = 1.5-6.9) and OR
      = 4.72 (95% C1 = 1.8-12.5), respectively. These jobs include typists/secretaries,
      nursing personnel, production workers and housewives. CONCLUSION: Evaluation of a
      general group of examinees referred for electrophysiological studies on
      sympathology compatible with CTS may show that occupational risk factors play a
      substantial role in the development of symptoms. By increasing the awareness of
      clinicians and the public to these risk factors, appropriate preventive measures
      can be introduced and the burden of the disease reduced.

PMID- 11519380
TI  - Fixed-dose combination therapy in the United States, Britain and Israel.
AB  - BACKGROUND: Fixed dose combination therapy varies among countries. OBJECTIVE: To
      compare the list of fixed-dose combination therapies used in the USA, UK and
      Israel. METHODS: The total list of drugs and FDC drugs were counted manually from
      a list of generic names. We also counted the number of drugs in four
      characteristic subgroups: cardiovascular, anti-infective, gastrointestinal, and
      dermatological. Data for drugs in the USA, UK and Israel were taken from the
      Physician's Desk Reference (PDR 1997), the British National Formulary (BNF March
      1997) and the Monthly Ethical Drug Indexed Compilation (MEDIC July 1997)
      respectively. RESULTS: The global percentage of FDC drugs in the USA and UK was
      higher than in Israel (20%, 25% and 15% respectively). A similar trend was found
      in all subclasses of FDC drugs except for the anti-infective category in which
      the percentage of FDC drugs was low and similar in all countries. CONCLUSION: The
      list of FDC drugs varies greatly between the USA, UK and Israel, reflecting the
      differences in the outcome of debate between the pharmaceutical companies and the
      regulatory authorities.

PMID- 11519381
TI  - Achilles tendon pain and related pathologies: diagnosis by ultrasonography.
AB  - BACKGROUND: When encountering complaints of pain in the area of the Achilles
      tendon, the clinician seldom reaches a correct and precise diagnosis based solely
      on the grounds of physical examination and standard X-rays. OBJECTIVES: To assess
      the usefulness of ultrasound in diagnosing pathologies of the Achilles tendon.
      METHODS: We conducted a retrospective review of patients presenting at our
      orthopedic clinics. RESULTS: Sonography was used to evaluate 41 patients with
      achillodynia. This modality enabled the diagnoses of 19 abnormal tendons (46%),
      peritendinous and other lesions; a complete rupture in two patients (5%); a
      partial rupture of the Achilles tendon in 3 (7%); various degrees of
      calcification of the tendon in 7 (17%); and peritendinous lesions discerned by
      the tendon's hypoechoic regions with disorganized arrangement of collagen fibrils
      in 4 patients (10%). Other lesions included tendonitis (3 patients, 7%),
      retrocalcaneal bursitis (3 patients, 7%), lipoma (1 patient, 2%), and foreign
      bodies (2 patients, 5%). The mean diameter of the pathological tendons was 10.4
      +/- 2.7 mm, while normal tendons measured 5.2 +/- 0.8 mm (P < 0.001). CONCLUSION:
      As in many other soft tissue lesions, ultrasonography is a useful tool in the
      evaluation of the underlying pathology in patients presenting with achillodynia.

PMID- 11519382
TI  - Breast cancer screening in two multicultural family practice teaching clinics.
AB  - BACKGROUND: Breast cancer is one of the most prevalent malignancies in women, yet
      one of the most treatable. Early detection is essential to obtain the desired
      remission and longevity. Numerous studies have shown that periodic screening for
      breast cancer can reduce mortality by 20-30%. OBJECTIVE: To assess the rates,
      compliance, characteristics as well as barriers in women regarding mammography
      screening. METHODS: The study group comprised a random sample of 702 women aged
      50 or older from 5,914 eligible women in two teaching clinics in southern Israel.
      Phone interviews using structured questionnaire were conducted. RESULTS: The mean
      age of the study population was 61 years. The vast majority of the women were not
      born in Israel. Sixty-three percent of the women had undergone a mammography
      screening, 48% in the past 2 years. Monthly self-breast examinations were
      performed by 12% of the women in the last 2 years. Significant factors associated
      with undergoing mammography were: more than 7 years since immigration, married, a
      higher education level, adequate knowledge about breast cancer and mammography,
      presence of past or current cancer, and cancer in relatives. The main reasons for
      not being screened was no referral (54%) and a lack of knowledge about breast
      cancer and mammography (19%)--conditions easily remedied by physician counseling.
      CONCLUSION: The study suggests that promotional efforts should be concentrated on
      new immigrants and on less educated and unmarried women.

PMID- 11519383
TI  - Characteristics of patients at a complementary medicine clinic in Beer Sheva:
      summary of the first two years of operation.
AB  - BACKGROUND: "Complementary medicine" incorporates several methods of treatment,
      all of which aim to promote the health and quality of life of the patient. Public
      interest and demand for complementary medicine services have increased in recent
      years in Israel, as they have throughout the western world. OBJECTIVE: To
      characterize patients attending the Complementary Medicine Clinic in southern
      Israel at the completion of its first 2 years of operation. METHODS: Data for 398
      patients selected at random from 4,400 patients treated in the clinic were
      collected retroactively from the patients' charts. RESULTS: Of those who visited
      the clinic, 68% were women with an average age of 49 years. Patients attending
      the clinic had higher rates of hypertension (20%), diabetes (6%) and heart
      disease (7%) than the general population of patients insured at the Clalit Health
      Services in the southern region. In addition to musculoskeletal problems (47%),
      the other most common complaint was emotional problems (13%) such as tension and
      anxiety. Acupuncture and Shiatsu were the most commonly used types of treatment
      (61%). Homeopathy was used by 7%. Among patients with musculoskeletal problems,
      there were significantly more men than women (P = 0.02), the mean age was higher
      (P = 0.07), and more of them were referred by friends or family (P = 0.06) than
      those with other problems. CONCLUSIONS: Characterizing patients attending a
      complementary medicine clinic is important for the planning of marketing and
      resource management, and can assist primary care physicians in decisions
      regarding the referral of patients to this type of healthcare.

PMID- 11519384
TI  - Post-psychotic depression in schizophrenia.
AB  - Although a depressive state is known to occur following the resolution of an
      acute psychotic episode, little research has investigated its etiology, course,
      prognosis and treatment. Very often the depression is mistaken for an
      extrapyramidal-like syndrome--the secondary effect of antipsychotic medication-
      as a sense of inevitability assails both the patient and therapist. Post
      psychotic depression, far from being an obscure and undefined clinical picture,
      has the characteristics of a clear-cut syndrome. Nevertheless, it was only
      recently referred to as a distinct entity in psychiatric classification systems.
      As a result, different researchers used varying criteria for the definition of
      the phenomenon, and the data collected in the different studies are therefore
      difficult to compare. We present a critical review of the data published to date,
      with emphasis on the importance of early recognition and treatment of post
      psychotic depression.

PMID- 11519386
TI  - New concepts on the pathogenesis of autoimmune disease.

PMID- 11519385
TI  - Gilbert's syndrome--clinical and pharmacological implications.

PMID- 11519387
TI  - Prophylactic gastroenterostomy for unresectable pancreatic carcinoma.

PMID- 11519388
TI  - Changes in drug economy in Israel's health maintenance organizations in the wake
      of the National Health Insurance Law.
AB  - BACKGROUND: It is not clear to what extent the drug economy in Israel's health
      maintenance organizations is responsive to major healthcare reforms. OBJECTIVE:
      To provide information on how drug expenditures, revenues, net costs and drug
      utilization have changed in the wake of the 1995 National Health Insurance Law in
      Israel. METHODS: This study compares trends in aggregate sick fund expenditures,
      revenues (patient co-payment) and net costs (expenditures less revenues) in
      Israel's four health maintenance organizations for the 3 year period 1992-1994
      prior to the introduction in 1995 of the NHI Law, with that of the 4 year period
      1995-1998 following its introduction. This analysis is similarly carried out for
      Israel's largest HMO, Clalit Health Services, and for the three smaller HMOs
      combined. RESULTS: The pace of growth in the pre-NHI era in drug expenditures and
      particularly in drug revenues was drastically reduced in the NHI era--whether
      measured as totals or as per insured person (age-adjusted) or in real terms at
      constant medicine prices. These trends were mirrored to a large extent in Clalit
      and in the other HMOs, with some important differences noted between the HMOs.
      Despite declining growth rates in drug expenditures and net costs, the proportion
      of these measures of the total HMO economy actually increased in the NHI era,
      reversing the trend seen in the pre-NHI era. CONCLUSIONS: The impact of the NHI
      Law on the HMO drug economy has been substantial. The evidence suggests a decline
      in both the qualitative (basket of drugs consumed) and quantitative (volume of
      drugs consumed) elements of growth. These changes in expenditure and revenue
      trends are discussed in the light of the evolving involvement of the Israel
      Ministry of Health in drug policy within the framework of the NHI, with emphasis
      on the basket of drugs reimbursed and co-payments for prescriptions.

PMID- 11519389
TI  - Trends in youth mortality in Israel, 1984-1995.
AB  - BACKGROUND: Investigation of causes of death can help inform intervention policy
      aimed at reducing preventable mortality. OBJECTIVES: To assess mortality causes
      and trends over time and identify target groups with excessive mortality rates
      among Israeli youth aged 10-24, in order to formulate an intervention policy for
      prevention of adolescent mortality. METHODS: Mortality data for Israeli residents
      aged 10-24 were extracted from the Central Bureau of Statistics computerized
      death certificate file for the period 1984-95. Trends were evaluated by cause of
      death and demographic characteristics. RESULTS: The crude mortality rate among
      Israeli youth aged 10-24, during 1993-1995, was 39.6 per 100,000. Rates were 2.7
      times higher among males, increased with age, and reached a peak among 18-21 year
      olds. Rates were 1.4 times higher among Arabs than among Jews. The sharp increase
      in mortality among Jewish males of military service age (18-21 years) was due
      mainly to motor vehicle crashes and suicide. Although overall mortality decreased
      by 9.4% from 1984-86 to 1993-95, the gap between the subgroups increased. MVC
      related mortality increased over time by 100% among Arab males. The rate of
      completed suicide among Jewish males increased by 110%. Although injury-related
      mortality is lower in Israel compared with the U.S., similar demographic
      differentials and trends were found in both countries. CONCLUSIONS: Suicide among
      Jewish males of military service age, as well as MVC fatalities among Arab males,
      present a growing public health issue. Intervention strategies should therefore
      be targeted towards these subgroups in order to minimize the rates of preventable
      death.

PMID- 11519390
TI  - Preventive geriatric medicine: reality or fiction?

PMID- 11519391
TI  - My love affair with geriatric medicine.

PMID- 11519392
TI  - Gastrointestinal tract cytomegalovirus infection with prolonged vomiting and
      fever in an immunocompetent child.

PMID- 11519393
TI  - Wandering spleen in a young girl with Gaucher disease.

PMID- 11519394
TI  - Breast cancer metastasizing to the rectum.

PMID- 11519395
TI  - Ischemic colitis--a case of triple senses diagnosis.

PMID- 11519397
TI  - Battling cancer through cooperation: Israeli-Palestinian conference on GI
      oncology--from the bench to the bedside.

PMID- 11519396
TI  - Ovarian vein thrombosis--computerized tomography diagnosis.

PMID- 11519398
TI  - Comprehensive management of patients with type 2 diabetes: establishing
      priorities of care.
AB  - Type 2 diabetes is a complex metabolic disorder characterized by elevated blood
      glucose levels and a marked increase in the risk of cardiovascular disease (CVD).
      The increased CVD risk is caused by a unique cluster of metabolic abnormalities,
      including dyslipidemia, hypertension, insulin resistance, and hyperglycemia. To
      reduce the risk of cardiovascular complications in patients with type 2 diabetes,
      comprehensive management of risk factors is essential. Aggressive treatment of
      dyslipidemia and hypertension is known to benefit patients with type 2 diabetes.
      In addition, intensive glycemic control and targeted treatment of insulin
      resistance can further reduce the enormous burden of CVD in this high-risk
      population. Increasing evidence suggests that insulin resistance is one of the
      earliest markers of risk for both CVD and diabetes, and it is known that insulin
      resistance alone can significantly increase the risk of CVD. Type 2 diabetes and
      insulin resistance are both associated with disordered lipid metabolism, manifest
      in elevated triglyceride levels, low levels of high-density lipoprotein
      cholesterol, and small, dense low-density lipoprotein cholesterol particles.
      Patients with type 2 diabetes and insulin resistance have an increased risk of
      hypertension, which further contributes to their CVD risk. Each of these factors
      can also contribute to the risk of microvascular disease. To ensure that patients
      with type 2 diabetes receive comprehensive, high-quality care, specific standards
      have been developed. These standards can help providers establish clear treatment
      targets, identify specific priorities of care, and use therapies of known
      efficacy to reduce the risk of complications. This review summarizes the current
      standards of care for patients with type 2 diabetes, with an emphasis on
      treatments that reduce the cardiovascular risk factors. Using a case study
      approach, it reviews the essential components of diabetes care and proposes a
      rational approach to these complex cases--an approach that should result in
      consistent, high-quality care.

PMID- 11519399
TI  - [Some aspects of the formation of the immune system organs in newborn rats born
      to females with chronic hepatitis].
AB  - The immune system organs formation and development was studied in 61 rat
      younglings born to pregnant animals with chronic toxic hepatitis. A comparative
      investigation permitted ascertaining that chronic heliotrine hepatitis in female
      rats results in an increased death rate in the progeny, the highest mortality
      being recordable at day 1 to 3 after birth. The surviving live younglings reveal
      against the background of thymus hypoplasia a significant inhibition of processes
      of formation of the peripheral immune organs lymphoid tissue.

PMID- 11519400
TI  - [Morphological and functional markers of the histo-hematological barrier in
      experimental hypercholesterolemia].
AB  - Results of the experiments carried out have shown that in experimental
      hypercholesterinemia it is disordered microcirculation together with mediated
      changes in permeability of the histohematic barrier, lipoprotein-rich plasma in
      the pericapillar space, with the organ parenchyma trophicity getting compromised
      that are primarily responsible for the presence of dystrophy and fibrosis of
      organs. Unidirectionality and systemic pattern of the reaction is evidence of a
      generalized character of affections of the terminal vascular bed in response to
      exposure to one of the risk factors for atherogenesis, viz, exogenous cholesterin
      and dyslipidemia.

PMID- 11519401
TI  - [Atypical neurological symptoms in pleural diseases].
AB  - Referring to data from the published literature the authors have given a well
      grounded description of the pathogenesis of nontypical neurological symptoms in
      disorders of the pleura. The presented observations clearly show that there is a
      possibility for errors to occur in making a differential diagnosis of the medical
      conditions under consideration.

PMID- 11519403
TI  - [Clinical and laboratory efficacy of triovit in patients with grade I renal
      impairment].
AB  - Results are submitted of the investigation designed to study efficacy of the use
      of the antioxidant drug "Triovit" in patients with chronic glomerulonephritis and
      chronic pyelonephritis in grade I chronic renal impairment (CRI). It has been
      ascertained that the use of the drug triovit results in activation of the
      antioxidant system which is noted to be depressed in CRI patients. The above drug
      was found to lower a toxic effect of lipid peroxidation at the level of membrane
      structures and body as a whole, with rate of CRI progression tending to slow
      down.

PMID- 11519402
TI  - [Comparative efficacy of diclobrou for prophylaxis of NSAID-associated
      gastropathies in patients with osteoarthritis].
AB  - As may as 155 patients with exacerbated osteoarthrosis were examined to compare
      the incidence of development of erosive-and-ulcerous lesions in the
      gastroduodenal system under exposure to different schemes of nonsteroid
      antiinflammatory drug (NAID)-therapy and over different time ranges of its
      administration and to assess prophylactic efficacy of the drug diclobrou
      (enterosoluble form of diclofenac natrium). There has been endoscopically
      validated usefulness of employing enterosoluble and injectable dosage forms
      during the first days of NAID-therapy. With signs of synovitis still in place,
      subsequent therapy treatments are to be administered with selective inhibitors of
      cyclooxigenase-2 or a simple dosage form of diclofenac should be combined with
      misoprostol.

PMID- 11519404
TI  - [Clinical use of catomas and biotrit in a combined treatment of patients with
      chronic neurodermatitis].
AB  - In 170 patients with neurodermatitis, therapeutic benefit was studied of two new
      antioxidant drug preparations catomas (containing beta-carotene and tocopheroli
      acetas) and biotrit (extractum from the sprouting wheat). Catomas was used in
      applications to the area of affection with the aid of phonophoresis, biotrit in
      injections. It has been shown by the studies made that employment of the above
      drugs combined with sedatives, desensitizing and anti-inflammatory means of
      remediation enhances efficiency of the treatments administered, which fact was
      evidenced by the reduction of the mean duration of the treatment undergone by 4.4
      days and by 30% increase in the treatment efficiency. Greater benefit from
      catomas and biotrit will be seen in those patients having been placed on a
      general treatment.

PMID- 11519405
TI  - [Experience gained with the drug amizon in the treatment of patients with mumps,
      with special reference to its effects on some biochemical markers].
AB  - Effectiveness was studied of a new drug amyzonum in a complex therapy of mumps in
      149 patients versus the group of 177 patients having been treated with
      conventional methods only. A positive effect was shown of the drug on clinical
      indices, with the incidence of complications having gotten lower, biochemical
      indices having returned to normal.

PMID- 11519406
TI  - [Use of refortan in a complex therapy of intraoperative hemorrhage as a method of
      preservation of blood in pelvic operations in oncology patients].
AB  - Admitting the possibility of the surgical patient developing immunological
      incompatibility, danger of his catching an infectious disease, and a risk of
      technical errors we are obliged to review conceptions of transfusion of donor
      blood. A negative impact of hemotransfusions on the frequency of recurrencies and
      metastasizing in operations for malignant tumours has been amply demonstrated
      together with a rise in the incidence of postoperative pyo-inflammatory
      complications. Employment of blood-preserving methods in surgery permits avoiding
      transfusion of donor blood preparations. One of the main methods for blood
      preservation is pre- and intraoperative hemodilution involving the use of
      synthetic colloidal solutions. It has been shown in our studies that employment
      of refortan (hydroxyethyl starch--HES 200/0.5-6%) in a complex of preoperative
      infusion therapy permits dealing with hypovolemic disturbances effectively,
      cutting down preoperative preparation time. Intraoperative use of refortan
      obviates the need for transfusion of donor blood preparation in hemorrhage up to
      20% of CBV. In a dose of 8-10 mg/kg, refortan prevents development of profuse
      hemorrhage-associated critical states.

PMID- 11519407
TI  - [Chavanprash in the treatment of hyperplastic processes in the endometrium].
AB  - Hyperplastic processes in the endometrium are classified as a common
      gynecological pathology. The drug chavanprash has been shown to improve general
      bodily resistance, to enhance vital tone of the body. It is endowed with a
      manifest hepatotropic and antitoxic activity, which fact permits recommending it
      for use in the combination therapy of hyperplastic processes in the endometrium
      as well as during the period of rehabilitation in the wake of the course of
      hormonotherapy.

PMID- 11519408
TI  - [Physiological adaptation reactions in patients with ischemic heart disease].
AB  - The condition was studied of bodily general adaptive reactions in patients with
      different forms of ischemic heart disease (IHD). Unlike healthy subjects, IHD
      patients displayed predominance of pathogenetic and dysadaptive type reactions.
      88 percent of healthy subjects had reactions of sanogenetic character, with 31.1
      percent of cases having been found in IHD patients. The spectrum of bodily
      general adaptive reactions was also distinctive in patients with different forms
      of IHD.

PMID- 11519409
TI  - [Prevalence of silent myocardial ischemia in hypertensive patients and risk
      factors].
AB  - Data are presented on the prevalence of and risk factors for silent myocardial
      ischemia in hypertensive patients suggesting to us that the endothelium
      dysfunction has very important part in the development of silent myocardial
      ischemia and that the degree of the endothelium dysfunction is related to the
      duration of silent myocardial ischemia in hypertensive patients.

PMID- 11519410
TI  - [Effects of korinfar-retard on parameters for the left ventricular diastolic
      function in patients with hypertensive disease].
AB  - Enrolled in the study were 52 patients with stage II-III disordered relaxation
      type diastolic dysfunction of the left ventricle and that of the restrictive
      type. All patients underwent echocardiography and doppleroechocardiography before
      and after having been placed on corinfarretard, 10 to 20 mg daily. The duration
      of the course of treatment was in the average 19.4 +/- 1.51 days. There was an
      improvement in patients on the above treatment on parameters associated with the
      temporal patterns of the diastole, those patients with disturbed relaxation type
      dysfunction having derived the greatest benefit from it. In patients with
      restrictive type diastolic dysfunction of the left ventricle, no significant
      changes were revealed in the diastole related to the drug in question.

PMID- 11519411
TI  - [Assessment of feasibility of using indices for heart rate variability in the
      differential diagnosis of renal parenchymal arterial hypertension].
AB  - 24-hr monitoring of the heart rate variability (HRV) was instituted in 72
      patients with essential hypertension (EH) and 68 patients with chronic
      glomerulonephritis (CGN) to establish differential-diagnostic criteria for EH and
      CGN. Clear-cut differences have been ascertained in changes in HRV in EH and CGN
      as evidenced by the results obtained.

PMID- 11519412
TI  - [Endothelial-protective effects of enalapril in hypertensive patients].
AB  - In the article data of endotheliumprotective effect of enalapril in hypertensive
      patients with varying degree of systemic hypertension are presented. The above
      effect was assessed by changes in activity of the von Willebrand factor and
      degree of arterial vessels dilatation in response to infusion of acetylcholinum.

PMID- 11519413
TI  - [Clinical significance of urinary albumin excretion in patients with essential
      hypertension].
AB  - In the studies made, the role of microalbuminuria as a diagnostic marker of
      greater load of essential hypertension in the examined patients has been
      ascertained.

PMID- 11519414
TI  - [Effects of nebivolol, metoprolol and enalapril maleate on the state of
      endothelium-dependent arteriolar vasodilation in patients with essential
      hypertension].
AB  - Effects were studied of nebivolol, metoprolol and enalapril maleat on the state
      of endothelium-dependent vasodilatation of arterioles in patients with essential
      arterial hypertension. Nebivolol has been shown to effectively decrease blood
      pressure and restore endothelium-dependent vasodilatation to a grater degree,
      than enalapril or metoprolol.

PMID- 11519416
TI  - [Effects of mechanical and biological stress factors on the phospholipid
      composition of the myocardium].
AB  - Effects have been studied of the technogenic and biogenic stress-factors on the
      myocardial phospholipid composition in white rats. It has been ascertained that
      the action of the technogenic stressor on the organism results in derangement of
      adaptive mechanisms in the myocardium, that of the biogenic stressor causes
      activization of adaptive mechanisms. The obtained results suggest to us an
      important ethiopathogenetic role of technogenic stressors in the development of
      myocardial pathologies.

PMID- 11519415
TI  - [Use of medications for the correction of functional disturbances in
      hemocoagulation and lipid peroxidation in patients with infectious myocarditis].
AB  - Disturbances were studied in the system of hemostasis, lipid peroxidation,
      functional condition of the cardiac muscle in patients with acute mild,
      moderately severe, and severe viral myocarditis. The studies were made before and
      after the treatment of patients with basal drug preparations, heparin,
      antioxidants (thiotriasaline, captopril). Therapeutic benefit from treatment with
      heparin, thiotriasaline was but insignificant in patients with mild, moderately
      severe, and severe course of the disease. It was only with the adoption of a
      complex therapy (basal drug preparations, heparin, thiotriasaline, captopril,
      diuretics) that patients derived clinical-and-laboratory-instrumental-and-social
      and-economic benefit from treatment.

PMID- 11519417
TI  - [Some aspects of the clinical course of infectious endocarditis in different age
      groups].
AB  - Differences were recordable in the course of infectious endcarditis in patients
      at different ages (young, middle-aged, elderly, senile, n = 85).

PMID- 11519418
TI  - [Urinary potassium excretion in chronic heart failure].
AB  - Mechanisms were studied of urinary potassium excertion in patients with chronic
      heart failure (CHF). A total of 78 patients were examined presenting with
      functional class I-IV CHF.

PMID- 11519419
TI  - [Use of isosorbide dinitrate and antagonists of angiotensin II in patients with
      stable angina pectoris in early stages of cardiac insufficiency].
AB  - Effects were studied of isosorbite dinitrate and antagonists of angiotensin II in
      patients with stable angina presenting with incipient stages of cardiac
      insufficiency. Changes in the ejection fraction, phases in passive and active
      filling of the left ventricle can be used as a prognostic criterion for
      efficiency of a long-term combined therapy involving the use of isosorbid
      dinitrate and renitec or cozaar.

PMID- 11519420
TI  - [Rehabilitation of invalids presenting with trauma sequelae in a complex of
      measures to reduce disability rates].
AB  - Prophylaxis of traumatism is administered with the aid of a corresponding
      committee on the regional state administration to improve a specialized care
      delivery to those persons having sustained injuries; we use a thorough analysis
      of the traumatologists' and surgeons' errors (according to phi. 088-y) followed
      by discussion at regional conferences with the above specialists taking part in
      it; the raising of the level of rehabilitation is effected through perfection of
      continuity of work carried on by MSEC and MCC, introduction of more practical
      forms for developing programs of rehabilitation of disabled persons. The first
      results of this work are encouraging.

PMID- 11519421
TI  - [Prerequisites and some aspects of hospitalization of patients with glomerular
      nephritis].
AB  - Data are submitted on the pattern of reasons for hospitalization,
      rehospitalization of patients with glomerulonephritis depending on the purpose
      and duration of the in-patient care over three-year activity of the regional
      nephrologic department. The authors have come to the conclusion that it is
      necessary that an expert evaluation of quality of diagnosis and treatment of
      glomerulonephrities patients should be carried out, which measure will, we
      believe, help in uncovering the existing shortcomings and their causes during
      stages of medical care delivery and in finding ways for improvement of the system
      of the nephrological service with special reference to such kinds of it as day
      clinics and domociliary medical services.

PMID- 11519422
TI  - [Classification of fractures of the proximal end of the femur].
AB  - Experience gained in different countries of the world with the use of existing
      classifications of the femur proximal end fractures (Muller, Pauwels, Garden) is
      discussed together with observations by Klenerman, Linton, Dorne, Erandsen,
      Kocher, and Nils Carlquist's scheme. Also submitted in the paper is the author's
      variant of classification based on characterization of the patient with regard
      for his/her concomitant afflictions, characteristics of the fracture sustained,
      the site of the fracture-related changes in blood supply.

PMID- 11519423
TI  - [Genetic consequences of ionizing radiation of parents on their offspring (review
      of the literature)].
AB  - The article is a review of the current published literature concerning possible
      genetic sequelae of exposure of human beings to ionizing irradiation. Data are
      submitted obtained from studies by leading specialists in radiation medicine and
      radiation biology.

PMID- 11519424
TI  - [Development of sex characteristics in adolescents in the forest regions of
      Ukraine].
AB  - A total of 3019 adolescents were examined residing in those territories of the
      Zhitomir and Vinnitsa Regions affected by radionuclide contamination, who ranged
      from 15 to 18 years old. Revealed in the above juvenile population was a
      stimulating effect of small doses of ionizing radiation on some parameters
      characterizing somatosexual development in adolescents 15 years old, that tends
      to smooth down with stabilization of physical and sexual development.

PMID- 11519425
TI  - [Current problems of social psychiatry in Ukraine].
AB  - Statistical data on mental diseases in Ukraine are presented, main trends of
      development of social psychiatry are outlined, ways for reformation of the social
      and-psychiatric service are submitted.

PMID- 11519426
TI  - [Effects of inhibitors of angiotensin-converting enzyme combined with antagonists
      of angiotensin II receptors on endothelial function in patients with chronic
      cardiac insufficiency].
AB  - Effects were studied of a combined therapy with inhibitors of the angiotensin
      converting enzyme and antagonists of receptors to angiotensin II on the
      functional condition of the endothelium in patients with chronic cardiac
      insufficiency (CCI). Recordable in the study was a noticeable decrease in the
      level of endothelin-1 and higher values for the concentration of 6-keto
      prostaglandin (PGF1 alpha) and cGMP. In that way, administration of inhibitors of
      the angiotensin-converting enzyme combined with antagonists of receptors to
      angiotensin II has, been shown to considerably improve the endothelial function
      in CCi patients, which fact will, we believe, help in raising clinical
      effectiveness of the above combined medication.

PMID- 11519427
TI  - [ATP activity of myocardial actomyosin complex in patients with dilated
      cardiomyopathy].
AB  - ATP activity of actomyosin in dilated cardiomyopathy (DCMP) was studied together
      with impact on the above activity of tropomyosin-troponin regulatory complexes
      recovered from the normal myocardium and cardiac muscle of a DCMP patient.
      Recordable in DCMP was a striking decline (1.5-fold) in ATP activity of
      actomyosin. But no significant difference was to be seen in sensitivity to Ca2+
      ions of actomyosins obtained from the normal myocardium and cardiac muscle of the
      DCMP patient. The cardial tropomyosin-troponin regulatory complex from the DCMP
      patient's myocardium was shown to be endowed with somewhat more manifest activity
      compared to the analogous complex recovered from the normal myocardium.

PMID- 11519428
TI  - [Impact of menopause and disease on osteocalcin markers in female patients with
      rheumatoid arthritis].
AB  - The impact of menopause and activity of rheumatoid inflammation on the osseous
      tissue metabolism was studied with the aid of biochemical markers of remodelling
      of the osseous tissue. Osteocalcin (noncollagenous protein of bone tissue) is
      believed to be the most informative marker of formation of the osseous tissue. In
      70 female patients presenting with rheumatoid arthritis, blood serum
      concentration of osteocalcin was measured. Of these, 37 were in their
      premenopause, 33--in postmenopause. The control group was 26 female subjects. The
      activity of the rheumatoid process in premenopausal period and during the
      postmenopausal second and third five-year periods was found out to be associated
      with the rate of processes of bone tissue formation. At menopause the blood
      content of osteocalcin gets increased but subsequently it is noted to be on the
      decrease.

PMID- 11519429
TI  - [Some aspects of cerebral autonomic vascular dystonia in patients with mitral
      valve prolapse].
AB  - Some aspects of origination of vegetovascular dystonia (VVD) in patients with
      mitral valve prolapse are considered. Forms of VVD manifestation are presented.
      Possible causes of VVD development accompanying mitral valve prolapse are
      analyzed. Original investigations have been carried out designed to study the
      condition of cerebral bloodflow in those patients suffering from VVD as a
      manifestation of mitral valve with the aid of the transcranial dopplerography
      technique. The authors have come to the conclusion that it is necessary for us to
      use a differentiated approach toward choosing a corresponding policy of managing
      patients.

PMID- 11519430
TI  - [Effects of hyperbaric oxygenation on the dynamics of clinical manifestations and
      deviations in the functional state of the pituitary-thyroid system in hypotensive
      type vegetovascular dysfunction in adolescents who had perinatal effects on the
      central nervous system].
AB  - Overall 157 adolescents who ranged from 11 to 14 years old were examined. Of
      these 88 had hypotensive type vegetovascular dysfunction, 69 were essentially
      healthy and comprised the control group. All examinees presenting with
      hypotensive type vegetovascular dysfunction had the history of perinatal
      affection of the central nervous system. The standard treatment was given to 22
      adolescents, treatments involving hyperbaric oxygenation were administered in 66
      children. Under hyperbaric oxygenation adolescents with vegetovascular
      dysfunction and perinatal affection of the central nervous system demonstrated
      reverse development of clinical symptomatology, normalization of functional
      activity of the pituitary-thyroid system, which fact permitted recommending the
      use of the method of hyperbaric oxygenation as a pathogenetic therapy.

PMID- 11519431
TI  - [A comparative analysis of changes in immune homeostasis in laparoscopic and
      conventional surgical interventions on the large intestine].
AB  - A comprehensive evaluation has been done of parameters characterizing cell-bound
      immunity, cytokinic profile, stress hormones (hydrocortisone), and C-reactive
      protein in a comparative aspect in those patients having undergone laparoscopic
      or conventional colectomy. The above indices were determined before surgery, in
      the early postoperative period, 24 h and 7 days subsequent to surgery.
      Laparoscopic surgical intervention was found out to lower somewhat the level of
      immunosuppression early in the postoperative course, which fact is manifested by
      retaining of expression HLA-DR on monocytes of the peripheral blood. Further
      randomized investigations should allow the final judgement about the degree of
      surgical stress.

PMID- 11519432
TI  - [Dynamics of interferon production during different phases of the pathological
      process in children with acute pneumonia and relapsing bronchitis].
AB  - With the purpose of gaining further insight into regularities of changes that
      take place in indices for the interferon status in children with acute pneumonia
      and current bronchitis depending on the phase of the pathological process, 112
      children were examined in whom the level of serum interferon was measured
      together with production of alpha- and gamma-interferon by leucocytes of the
      peripheral blood in vitro. It is shown that in the examined patients with acute
      pneumonia and relapsing bronchitis in the acute period and during the phase of
      reparation there are differences in functioning of indices for the system of
      interferon.

PMID- 11519433
TI  - [Lipid peroxidation and antioxidant defenses in neonates treated with exogenous
      surfactants].
AB  - Certain parameters were studied associated with lipid peroxidation (LPO) and
      antioxidant defense (AOD) in those newborn infants having been treated with the
      exogenous surfactant Alveofact (Boehringer Ingelheim, Germany). Kept under
      medical surveillance were 60 preterm infants presenting with primary pulmonary
      pathology and severe respiratory insufficiency aged 35 hours old. Of these, ten
      babies (the main group) received two dosages of the above drug, with the mean age
      at administration having been 17.36 +/- 6.54 hours. The time-related course was
      studied of the following parameters--lipid peroxidation potential (LPOP), non
      enzymic antioxidant activity (AOA), blood serum content of lipid hydroperoxides,
      uric acid, bilirubin, iron, catalase and lactatedehydrogenase activities. Those
      babies having been given the surfactant demonstrated significantly lower LPOP
      basic level and higher non-enzymic AOA in the blood serum, which fact was
      related, in the first place, to a high incidence of grave forms of respiratory
      distress syndrome. The administration of two doses of the surfactant with a
      therapeutic purpose had no effect on subsequent systemic indices for LPO and AOD.
      It has been found out that high LPOP and low enzymic AOD in preterm infants
      presenting with grave primary affliction of the lungs can be one of reasons for
      development of surfactant-deficient states, and account for an inadequate
      clinical effect of exogenous surfactant drugs and for a poor prognosis.

PMID- 11519434
TI  - [Five-years' experience in the use of extracorporeal shockwave lithotripsy at the
      Central Kiev Clinic Hospital].
AB  - The article focuses on the main aspects of treatment of urolithiasis with the aid
      of extracorporeal lithotripsy at the Central Kiev City Clinical Hospital with
      particular regard to the therapeutic policy of in-patient managing of patients.
      An analysis has been performed together with substantiation of connection between
      physical parameters of the focal zone and efficiency of lithotripsy, which
      attempts will, we believe, promote the accuracy of prognostication of the course
      of treatment.

PMID- 11519435
TI  - [Dynamics of markers and rheological properties of red blood cells in patients
      with hemorrhagic fever presenting with renal syndrome treated with trental and
      clivarin].
AB  - Hemorrhagic fever with the renal syndrome (HFRS) is a viral disease of zoonotic
      nature presenting with a polyorgan symptomatology, with the leading syndrome
      being essentially a hemorrhagic one. Studied in HFRS patients during different
      stages of treatment were morphological-and-functional features of erythocytes
      (E). As many as 65 HFRS patients presenting with varying degree severity of their
      trouble were examined. The control group comprised 15 subjects. E volume was
      studied together with content and concentration of hemoglobin (Hb) in one E.
      There have been estimated parameters characterizing aggregation (percentage of
      minimum/maximum aggregation, deaggregation factor, second wave of aggregation).
      Trental and clivarin were prescribed for the trouble. In severe and moderately
      severe course a decrease in Hb content and concentration in the early period was
      revealed as was an augmentation of E volume, with Hb level and hematocrit value
      tending to be on the increase. Changes in rheological parameters were manifested
      by higher percentage of minimum and maximum aggregation and decrement in the
      deaggregation factor by 55 percent as compared with the control group.

PMID- 11519436
TI  - [Role of viral infection in the pathogenesis of vulvar diseases].
AB  - A clinical assessment was performed of results of examination in 177 patients
      with dystrophies, dysplasias and carcinomas of the vulva. The presence of the
      viral infection was ascertained on the basis of cytological signs pathognomonic
      for specifically viral infection. Virus infection was identified in dystrophy in
      29 percent of cases, in mild displasia in 29 percent, in moderately severe in 31
      percent, in severe dysplasia in 33 percent of patients. There were 80 percent of
      infected subjects among those with carcinomas of the vulva, which fact suggests
      that virus infection plays its part in the pathogenesis of the pathology in
      question.

PMID- 11519437
TI  - [Cytochemical markers for intracellular glycogen in peripheral blood neutrophils
      in patients with gingivitis presenting with thyroid gland disorders, and after
      treatment with antioxidants].
AB  - Used in this paper is the material secured in the examination of 82 children aged
      11 to 14 years old presenting with thyroidal dysfunction, who had come from
      ecologically abnormal zones and placed on a rehabilitative treatment programme in
      the Eupatoriya sanatorium "Druzhba". Our objective in this work was to study
      effects of antioxidant therapy on parameters associated with intracellular
      glycogen in patients with gingivitis in the presence of a concomitant illness.
      The data obtained permitted coming to the conclusion that development of
      gingivitis is of a manifest energy-intensive character, with a concurrent morbid
      medical condition being an aggravating factor. The use of antioxidant therapy in
      a combined treatment of the above category stomatological patients was found to
      shorten time they receive their treatment. Other positive effects of the above
      therapy include prevention of complications and activation of glycogen-producing
      function of homeostasis.

PMID- 11519438
TI  - [Components of the metabolic syndrome in patients with arterial hypertension].
AB  - Analyzed in the paper is an association between known properties of a fully
      manifest metabolic syndrome (MS) and variants of combinations of arterial
      hypertension (AH) with hyperlipidemia (HLP) only or with only disturbed tolerance
      to glucose (DGT) or DGT + HLP. A total of 100 patients who ranged from 35 to 70
      years old were examined, in whom AH had been detected 4 to 10 years prior their
      enrollment in the study. In terms of criteria for putting MS components into
      groups, the greatest number of patients displayed AH concurrent with DGT and HLP
      (37.1%), fully manifest MS was in 20 percent of patients. Isolated AH was
      recordable in only 8.1 percent of patients. Both fully developed MS and its
      components (AH, HLP, DGT) have been shown to affect the accelerated rate of
      development of atherosclerosis-related cardiovascular diseases.

PMID- 11519439
TI  - [Helicobacter pylori infection as a cause of hypergastrinemia].
AB  - With the aid of the radioimmunologic technique, the content was studied of blood
      serum gastrin in healthy patients, those presenting with chronic gastritis under
      exposure to Helicobacter pylori (Hp+) and free from the infection (Hp-). The
      secured results suggest to us that (Hp-) patients have hypogastrinemia with
      antral localization of the pathological process. In (Hp+) patients, blood serum
      levels of gastrin are noted to be significantly higher than the analogous indices
      in essentially healthy subjects, (Hp-) patients presenting with antral- and
      pangastritis.

PMID- 11519440
TI  - [Microbial intestinal disturbances in children with frequent acute complicated
      pneumonia].
AB  - In the investigation designed to study intestinal microflora in children with
      acute complicated pneumonia having developed against the background of frequently
      recurring diseases such as acute respiratory infections, 91.1 percent of
      pediatric examinees demonstrated microecologocal disturbances in the intestines,
      with grade III dysbacteriosis in 46.6 percent. In that case the enterocolitic
      syndrome in pneumonia should be regarded as a clinical manifestation of
      disturbances in biocenosis of the intestines, in the functional capability of its
      microflora. Intestinal dysbacteriosis aggravates the course of acute complicated
      pneumonia in children at early ages and warrants a purposive therapy normalizing
      the intestinal microflora.

PMID- 11519441
TI  - [Pathogenesis of disturbances of the hemostatic system in neonates].
AB  - Described in the paper are chief pathogenetic mechanisms of development of
      disturbances in the hemostasis system in neonates born to mothers presenting with
      extragenital pathologies. Marked clotting changes were noted together with those
      in the system of the erythron. Recordable in the above infants were also vascular
      permeability disorders, abnormalities of metabolism. These changes were
      especially manifest in those children presenting with diabetic fetopathy and in
      babies born to mothers with neurocirculatory asthenia. The results secured
      permitted the development of the system of curative-and-prophylactic measures to
      be instituted in the above infants.

PMID- 11519442
TI  - [Current approaches to treatment of secondary sulfonylamide drug resistance in
      Type II diabetes mellitus].
AB  - A differentiated approach toward treating secondary sulfanilamide resistance in
      patients with type II diabetes and proposed therapeutic regimens simple enough to
      be adopted in the management of the patients in question permit achieving
      satisfactory hypoglycemic effect maintaining an acceptable level of glucose in
      the blood.

PMID- 11519443
TI  - [Iron metabolism: methods for the diagnosis of abnormalities. Current approaches
      for the treatment of iron-deficiency anemia. Review of the literature and case
      histories].
AB  - The paper contains a concise summary of information now available concerning
      bodily iron metabolism in human beings. Consideration is given to mechanisms of
      formation of iron deficiency. An analysis of present-day methods of diagnosis of
      iron deficiency during different stages of its formation is given. A protocol
      scheme for the drug aktiferrin to be employed in the patients has been developed,
      which fact permits normalizing indices for the peripheral red blood dispelling
      iron deficiency in those patients presenting with iron deficiency anemia.
      Pathogenetic mechanisms of disordered iron metabolism in the human organism are
      discussed together with correction thereof.

PMID- 11519445
TI  - [Positive experience gained with the administration of psychotherapy in patients
      in the acute period of craniocerebral injury].
AB  - In those patients in the acute phase of craniocerebral injury, psychoprophylaxis
      was administered together with acupuncture treatments subsequent to psychotherapy
      prescribed in addition to routine drug therapy. The policy of dealing with
      patients described above permitted securing the best results of treatment.

PMID- 11519444
TI  - [Etiotropic treatment of patients with early uterine carcinoma as a basis for
      prevention of relapses and complications].
AB  - In this paper, consideration is given to the role that etiological and
      pathogenetic factors have in the development of malignant tumours. Prevention of
      possible recurrencies and complications in patients with incipient forms of
      hysterocarcinoma warrant etiotropic treatment which has been shown to be
      effective and essential for the object to succeed in.

PMID- 11519446
TI  - [Diagnosis of peripheral vitreous chorioretinal dystrophies with the aid of a
      pathogenic test].
AB  - In diagnostic investigations, a concurrent relation was revealed between the eye
      stretching, hemodynamics, and presence of peripheral vitreochorioretinal
      dystrophy. A pathogenetically validated, requiring no equipment diagnostic test
      is proposed that predicts the presence of peripheral vitreochorioretinal
      dystrophies in some segment of the eyeball or other by measuring the temperature
      in the region of the ciliary body.

PMID- 11519447
TI  - [Problems of environmental health in the Republic of Armenia].

PMID- 11519448
TI  - [Small doses of ionizing radiation as radiation modifying factor].
AB  - To investigate the biological effects of small dose ionizing radiation has been
      acquiring greater importance. The awareness of how and in what direction it show
      its modifying effects in small doses is an essential scientific basis for
      developing standards, living conditions under specific environmental conditions.
      Cultured Hela cells and DEF 4/21 fibroblasts were used to evaluate the biological
      effects of small-dose ionizing radiation, by examining the conditions under which
      it showed its modifying effect in small doses (0.1 Gy) in particular. Preexposure
      to small-dose radiation was shown to alter cell responses to subsequent radiation
      in large doses. The modifying effects of small-dose radiation turned out to
      depend on the interval of exposure to small and large doses. Sensitization was
      recorded at an interval of 2-3 min; an adaptive response was achieved when the
      interval increased up to 3-5 hours. Upon exposure, intercellular contacts
      contribute to the modifying effects of small-dose radiation. There was neither
      effect of sensitization nor adaptive response if single cells were exposed to
      radiation.

PMID- 11519449
TI  - [Sanitary assessment of radon hazards in residential buildings].
AB  - The authors have constructed models including that of dose-effect of the content
      of decay products, that of the volumetric activity of radon in the apartments,
      and that of biological human responses. They have found specific features of
      female reproduction dysfunction, perinatal, general, and cancer morbidity and
      mortality. The maximum ineffective radon concentration upon chronic exposure has
      been established by using dosage simulation of the frequency of genetic disorders
      (small malformations).

PMID- 11519450
TI  - [Medical and ecological evaluation of mercury hazards to the population of the
      Irkutsk region].
AB  - Pollution of the Angara river with the waste water of chemical production has led
      to mercury accumulation in the ecological water system. Potential human hazard is
      associated with mercury cumulation in marketable fishes. The maximum levels of
      mercury were 1.5-4.0. Dietary mercury intake has been confirmed by that the toxic
      agent is present in the biological substrates of the rural population in amounts
      greater than the baseline values. An attempt has been made to predict the
      development of a situation by means of the logical model developed by the data of
      monitoring in Japan and Canada. The period of formation of a focus of
      ecologically caused mercurialness is estimated to be 100-200 years after the
      onset of sewage discharge into the water reservoir.

PMID- 11519451
TI  - [Effects of a complex of environmental pollutants in the mining and metallurgy
      industry areas on the offspring of F1 white rats].
AB  - The effects of a complex of ambient air pollutants in the mining- and metallurgy
      industry areas on the development of the generation F1 were studied in the
      experiments on albino rats. The complex of adverse chemical agents of the ambient
      air was found to exert a pronounced embryotoxic effects on the postnatal
      development of the generation F1, as manifested by a reduction in the measures of
      viability, lower size, impairments in the status and physiological development of
      the central nervous system, in the mechanism of formation of conditioned
      reflexes, and by the predominance of excitement over inhibition.

PMID- 11519452
TI  - [Role of the number of stories in the radiation-sanitary assessment of
      residential buildings].
AB  - Upon long-term exposure, the radioactive gas radon-222 and its decay products in
      increased doses adversely affect human health. Since the human being spends about
      65% of his time in the buildings, it is necessary to evaluate air radiation
      purity in the rooms, which can be obtained by making a sanitary radiological
      survey of residential buildings. The scope of the rooms in many-storeyed
      buildings to be examined can be considerably reduced if the regularities in radon
      distribution are known. This paper deals with searches for regularities in the
      distribution of radon levels by the floors of many-storeyed buildings in Tomsk.
      The room air concentrations of radon were measured for 18 residential buildings
      with tract detectors upon 1-3--month exposure. The findings showed a different
      pattern in the distribution of radon levels by the floors in relation to the
      structural features of a building and to the type of a building material. The
      wooden and slag-concrete buildings show a 2-3--fold increase in radon levels on
      the lower floors as compared to the upper ones. A statistical analysis of
      measurements in the bearing-wall and brick buildings revealed no association of
      the concentration of radon with the level of a floor, the distribution is near
      uniform with 15-30% standard deviation, which is within the limits of measurement
      error.

PMID- 11519453
TI  - [Use of complex indices of environmental air pollution for sanitary ranging of
      the territory of the South Administrative District of Moscow].
AB  - Whether complex indices of ambient air pollution can be used for sanitary ranging
      of primary facilities of the district was studied. The indices were calculated by
      using single air samples. The impact of "zero samples" on the results of
      calculation of the significance of differences in the single concentrations of
      individual chemical air pollutants was examined. The average annual
      concentrations of pollutants were calculated on the basis of average daily
      maximum allowable concentrations and the a-coefficient recommended by M. A.
      Pinigin. The database contains 20,000 definitions of the most hazardous chemical
      pollutants in the ambient air. Significant and insignificant values of chemical
      pollutants in single ambient air samples may be used in calculating complex
      indices as the rate of result coincidence was 80%, the suitability of
      insignificant values for ranging was confirmed in 81.25% of cases.

PMID- 11519454
TI  - [Role of environmental factors in perinatal pathology (review)].

PMID- 11519455
TI  - [The environment and human health. "Russia's ecological doctrine in the context
      of national stable development strategy"].

PMID- 11519456
TI  - [The state of the adaptation system of women during the postpartum period under
      the influence of an industrial complex].
AB  - The hormonal status was studied in the dynamics of postpartum stress in the
      puerperas who lived in the town of Balkhash under the influence of an industrial
      complex. The puerperas were found to show no pronounced adrenal cortical response
      to postpartum stress; there was monotony of changes in the content of dopa and
      dophamine and the levels of adrenaline and noradrenaline remained high on day 5
      after delivery as compared with the controls. There were high levels of prolactin
      and cortisole, which suggests different stress levels in Balkhash females and in
      the controls. It can be assumed that chronic exposure to industrial noxious
      agents results in so-called cross resistance caused by one stressor (delivery) in
      relation to the effect of other-order (ecological) stressors rather than in
      depletion of the hormonal system.

PMID- 11519457
TI  - [Hygienic environmental characteristics and population health in areas of
      production of heavy oils and natural bitumen].
AB  - The paper deals with the impact of production of heavy oil and natural bitumens
      on the environment and human health. It provides a sanitary characteristics of
      the degree of ambient air pollution, the quality of reservoir and drinking water
      and soil in the areas of production of heavy oil and natural bitumens. Human
      health was studied in all age groups by medical and demographic indices and
      diseases. Hydrocarbons, hydrogen sulfide, carbon oxide were found to be the
      leading pollutants in these areas. Production of heavy oil and natural bitumens
      pollutes surface and underground water-bearing horizons, which is a cause of
      worse conditions for the population to use water due to a 1.8-fold increase in
      water hardness and a 1.2-fold increase in the content of sulfates, chlorides, and
      nitrates, as compared to 1987-1991. The production of heavy oil and natural
      bitumens is a large source of soil pollution. The greatest soil pollution was
      observed in the areas of bitumen production by intraseam burning and vapour-heat
      exposure. There was a relationship of respiratory disorders to sulphur dioxide (r
      = 0.5-0.73) and hydrogen sulfide (r = 0.6-0.82), of blood and blood-forming organ
      diseases to nitrogen oxide (r = 0.58-0.79), and of nervous and sensory diseases
      to sulphur dioxide (r = 0.73-0.82). The study provided sanitary recommendations
      for environmental sanitation and health promotion in the areas of production of
      heavy oil and natural bitumens.

PMID- 11519458
TI  - [Hygienic assessment of aerosol air pollution by smokehouse waste].
AB  - The disperse phase of waste fumes forming during cold and hot fish smoking was
      studied by distributing the particles into 6 fractions, by determining phenols,
      acids, carbonyl compounds, and benz(a)pyrene (BP) in them, and by calculating the
      hazard index. In the waste fumes of cold smokers, the proportions of phenols,
      carbonyl compounds, and acid in the formation of the hazard index were shown to
      be 72.1 +/- 1.5, 19.6 +/- 1.3, and 5.9 +/- 0.3%, respectively. In the waste fumes
      of hot smokers, these figures were 67.3 +/- 1.1, 20.4 +/- 1.2, and 5.8 +/- 0.3%,
      i.e. the proportion of phenols in the formation of the hazard index was also
      prevalent. The hazard index for BP in the waste fumes of cold and hot smokers was
      120.9 +/- 1.7 and 230.8 +/- 8.1, respectively, which amounts to 2.4 +/- 0.2 and
      6.5 +/- 0.4% of the total hazard of smoke particles.

PMID- 11519459
TI  - [Optimization of water use by the Voronezh population].

PMID- 11519460
TI  - [Magnetic properties of women's footwear].

PMID- 11519461
TI  - [Sanitary characteristics of the production of asbestos membranes].
AB  - The paper presents preliminary results of sanitary assessment of the production
      of asbestos membranes. The production may emit highly disperse asbestos
      containing aerosols of disintegration with low levels of filamentous particles
      and respirable fibers of chrysotile-asbestos into the air of working areas. It is
      concluded that latest chrysotile-asbestos processing is not a significant source
      of air pollution in the working areas where asbestos-containing and related
      noxious substances are present.

PMID- 11519462
TI  - [Effects of working conditions in the production of synthetic rubber on workers'
      health].
AB  - Examination of 325 Kazan workers engaged in the production of synthetic rubber
      revealed a high (35.6%) prevalence of thyroid pathology. Patients with thyroid
      disease and apparently healthy workers manufacturing synthetic rubber were found
      to have lower levels of T3, T4, and zinc and higher levels of thyroglobulin
      antibodies and chromium in the serum than in apparently healthy individuals not
      contacting with noxious agents. The magnitude of increases in the workers' serum
      concentration of chromium was related to the length of service. The changes were
      more pronounced in patients with thyroid disease. Correlation analysis revealed
      that there were direct relationships between the serum levels of T3, T4, and zinc
      in all groups. There was an inverse correlation between the levels of T4 and the
      length of service in noxious production in the workers with thyroid disease.

PMID- 11519463
TI  - [Electrolyte metabolism in workers engaged in oil-refining industry].
AB  - The influence of unfavourable factors of the industrial environment on
      electrolyte balance in the red blood cells and plasma of workers engaged in
      petroleum-refining industry was studied. All examinees were divided into 3 groups
      in terms of the exposure to chemical pollutants: 1) workers unexposed to chemical
      pollutants; 2) those exposed to them 2-3 times a week; 3) those exposed
      constantly during their work for 3-5 years. A control group included individuals
      who were not engaged in chemical industry. Groups 2 and 3 showed decreases in the
      levels of K, Mg, and Ca and increases in the concentrations of Na and P in the
      red blood cells and in those of K, Mg, and P in the plasma while plasma Na and Ca
      reduced.

PMID- 11519464
TI  - [Functional music as a means of fatiguability relief and health preservation in
      an enterprise].

PMID- 11519465
TI  - [Actual nutrition and vitamin status of school children in the Orla region].
AB  - The actual nutrition and vitamin provision in 14-17-year-old schoolchildren in
      Oryol and the Oryol Region were studied within the framework of the working
      programme. Sanitary recommendations for vitamin prophylaxis were developed.
      Evidence is provided for the biomedical efficiency of vitamin prophylaxis.

PMID- 11519466
TI  - [Role of selenium in the etiology and prevention of diseases (review)].
AB  - The data of reports by Russian and foreign authors on the biological effect of
      selenium are summarized. Some investigations have revealed its high toxic and
      carcinogenic properties in the selenium-rich biogeochemical provinces. Low
      selenium diet has a human unfavourable impact. Recent studies have provided
      evidence for that is severe selenium deficiency in the environmental objects and
      foodstuffs virtually throughout the former USSR. At present selenium is
      recognized to be an essential trace element for human health. Selenium
      preparations in therapeutical doses have high antioxidative and anticarcinogenic
      activities. The types of medicinal plant materials that has a pronounced capacity
      to selectively accumulate selenium from the soil have been defined. Moreover,
      there are medicinal plants which are selenium concentrators that have high
      biological accumulation coefficients. Experimental and clinical findings indicate
      that selenium-containing drugs and medicinal plants should be recommended as an
      compulsory food additive in selenium-deficient areas for treatment and
      prophylaxis.

PMID- 11519467
TI  - [Effects of smoking on the external respiration system in adolescents and young
      adults].
AB  - The specific features of the function and apparatus of external respiration were
      studied in adolescent and juvenile smokers and non-smokers. Ninety three boys
      aged 14-16 years who were 8-10--form pupils and 130 young men aged 19-23 years
      who were University students were examined. It was found that 38.7% of
      schoolchildren and 26.2% were smokers. 61% of the non-smokers were recorded to be
      apparently healthy. This condition was encountered 1.2-1.6 times less frequently
      in the smokers. The same number of smokers and non-smokers were at risk for lung
      pathology that was detectable in the former 2-2.5 times more frequently. Most
      indices of the function and apparatus of external respiration were not different
      in the smokers and non-smokers and they were in the normal range. The exceptions
      were functional residual capacity and expiratory PO?? which are significantly
      higher in the smokers, which suggests that respiratory tissue is of higher
      airiness aimed at compensating for permanent or recurrent hypoxia.

PMID- 11519468
TI  - [Dynamics of physical development of Chuvash rural school children (1884-1999)].
AB  - Analysis of the statistic indices height and body weight in schoolchildren has
      demonstrated their positive changes in all age and sex groups for 115 years. The
      maximum height and body weight increases are observed in the time intervals 1962
      1966, 1966-1982 which show statistically significant increases in the indices in
      virtually age-sex groups. In the past 15 years height increases have preserved;
      however, their increase rate has decreased; there is a negative trend for body
      weight to change, which is more pronounced in girls. The findings suggest that
      there is a tendency for developmental acceleration to be stabilized, which are
      not contradictory to the global epochal processes of growth and development. The
      changes in body weight may be regarded as negative, which is caused by present
      socioeconomic problems in our country. Physical development monitoring in
      children and adolescents permits development and implementation of regional and
      federal programmes for health promotion to ensure the population's sanitary well
      being.

PMID- 11519469
TI  - [Gas chromatographic determination of 1,2,4-trichlorobenzene in the air of
      workplace].

PMID- 11519470
TI  - [Criteria for individual sensitivity to occupational noise].

PMID- 11519471
TI  - [Skin excretion of glucose in healthy young persons].

PMID- 11519472
TI  - [Modified methods of mycotoxin studies].

PMID- 11519473
TI  - [Identification of major components of environmental pollution by space
      photography data].

PMID- 11519474
TI  - [Teaching of child and adolescent health at higher medical school (on the 115th
      anniversary of teaching a school health course and the 75th anniversary of the
      foundation of the Department of Education Health--Child and Adolescent Health,
      Medical University, Moscow University, I. M. Sechenov First Moscow Medical
      Institute].

PMID- 11519475
TI  - Guidelines for the management of severe sepsis and septic shock. The
      International Sepsis Forum.

PMID- 11519476
TI  - JNV: gets better every year.

PMID- 11519477
TI  - Evaluation of HIV-1 Tat induced neurotoxicity in rat cortical cell culture.
AB  - In a substantial number of cases, Human Immunodeficiency Virus type 1 (HIV-1)
      infection causes neuronal cell loss and leads to the development of AIDS
      associated dementia. Several studies have suggested that both host and viral
      factors contribute to neuronal loss. Here we studied the effect of HIV-1 Tat in
      primary rat neuronal cells as a model to understand mechanism of neuronal cell
      death. At nano molar concentration, recombinant Tat induced cell death in primary
      rat mixed cortical neurons. Tat could also induce uptake of calcium in primary
      rat cultures. When cells were incubated with NMDA receptor antagonists, MK-801
      and D-CPP, cell death and 45Ca uptake were inhibited. Under similar conditions
      non-NMDA antagonists, NBQX, DNQX and CNQX, and sodium channel antagonist, TTX,
      did not inhibit Tat induced neuronal cell death. In a similar way HIV associated
      products from in vitro HIV-1 infected cells induced neuronal cell death which was
      inhibited by NMDA receptor antagonist. Results presented in this paper suggest
      that activation of NMDA receptors by HIV-1 Tat is responsible for neuronal cell
      death in primary rat cortical neurons.

PMID- 11519478
TI  - Functional analyses of natural killer cells in macaques infected with
      neurovirulent simian immunodeficiency virus.
AB  - Clearance of HIV and SIV from the peripheral blood by the cellular immune system
      lessens the viral burden in infected individuals and may have an impact on virus
      infection of the CNS and the development of CNS lesions. However, the role of
      immune responses in preventing or limiting CNS infection has not been clearly
      defined. We investigated the role of natural killer cells in the outcome of SIV
      infection of macaques as a model for humans with AIDS and HIV encephalitis. In
      our study, six pig-tailed macaques were infected with the neurovirulent virus,
      SIV/17E-Fr, and the immunosuppressive virus, SIV/ DeltaB670, in a model system
      that causes rapid progression to AIDS and a high frequency of CNS lesions. NK
      lytic activity in each macaque was monitored longitudinally. In addition, we
      enumerated NK cells and tested macaque PBMC for the ability to lyse SIV-infected
      target cells. We found that there was a significant inverse correlation (P=0.02)
      between the robustness of NK response and the development of CNS lesions. Animals
      lacking strong NK cell responses developed more severe CNS lesions than those
      with robust NK responses did. Furthermore, pre-infection levels of NK activity
      were predictive of CNS lesion severity. The macaque with the most robust pre
      infection NK activity developed no CNS lesions. In these infected macaques, NK
      activity was shown to be directed against SIV-infected cells. We extended these
      in vivo findings to delineate precisely which cell type was mediating this SIV
      directed lysis. We used both macaque and human cells to demonstrate that the
      population that mediated anti-SIV and anti-HIV cytolytic effects was NK cells.
      Furthermore, we showed that this anti-SIV and anti-HIV cytolytic effect was
      directed at the envelope protein and not gag proteins. Thus, NK cells have the
      capacity to recognize and lyse cells expressing SIV and HIV antigens. These data
      support a role for NK cells in the modulation of CNS disease.

PMID- 11519479
TI  - Mechanism of measles virus failure to activate NF-kappaB in neuronal cells.
AB  - Lack of IFN-beta and MHC class I expression in measles virus (MV) infected
      neurons could impair the host antiviral defense mechanism and result in virus
      escape from recognition by cytotoxic T-cells. Induction of IFN-beta and MHC class
      I gene expression requires NF-kappaB activation which depends on degradation of
      IkappaBalpha, an inhibitory protein of NF-kappaB. In earlier studies we
      demonstrated that in contrast to glial cells, MV was unable to induce
      IkappaBalpha degradation in neuronal cells. It is unclear whether this failure is
      due to the presence of a neuron-specific IkappaBalpha isoform or a defect in the
      MV signaling cascade that leads to IkappaBalpha phosphorylation and degradation.
      In this study, an IkappaBalpha-wild type (WT) expression vector was transfected
      into neuronal and glial cells and subsequently exposed to MV. In contrast to
      glial cells, IkappaBalpha-WT was degraded in neuronal cells in response to
      TNFalpha but not MV. The findings eliminate the existence of an IkappaBalpha
      isoform in neuronal cells that is resistant to phosphorylation by MV. Blocking de
      novo protein synthesis with cyclohexamide had no effect on neuronal IkappaBalpha,
      indicating that lack of degradation rather than increased synthesis is
      responsible for IkappaBalpha accumulation in MV-stimulated neuronal cells. To
      determine if malfunction in the MV receptor CD46 is responsible for failure of
      IkappaBalpha phosphorylation and degradation, neuronal cells were transfected
      with a wild type CD46 (CD46-WT) expression vector. MV stimulation of CD46-WT
      transfected cells failed to induce IkappaBalpha degradation. Collectively these
      findings indicate that failure of MV to phosphorylate neuronal IkappaBalpha is
      not due to a presence of an IkappaBalpha isoform or malfunction of the MV
      receptor, and is more likely to be due to a defect in the signaling pathway that
      normally leads to IkappaBalpha phosphorylation and degradation.

PMID- 11519480
TI  - Increased frequency of JC virus type 2 and of dual infection with JC virus type 1
      and 2 in Italian progressive multifocal leukoencephalopathy patients.
AB  - To verify the possibility of different role of JC virus genotypes in the etiology
      of progressive multifocal leukoencephalopathy, we analysed several JC virus
      isolates amplified from AIDS patients with and without progressive multifocal
      leukoencephalopathy and healthy controls by nucleotide sequencing. Cerebrospinal
      fluid (CSF), peripheral blood mononuclear cells (PBMCs) and urine from 52 AIDS
      patients suffering from various neurological diseases including 21 cases of
      progressive multifocal leukoencephalopathy, and PBMCs and urine from healthy
      subjects were evaluated by nested polymerase chain reaction (PCR) for the
      presence of DNA belonging to the highly conserved large T antigen (LT) of JC
      virus. The different JC virus subtypes were identified by nucleotide sequence
      analysis of the virion protein (VP1) genomic region. JC virus DNA was detected in
      all the CSF samples from the progressive multifocal leukoencephalopathy patients,
      but not in the CSF from non-progressive multifocal leukoencephalopathy cases,
      while the frequency of JC virus DNA detection in the PBMCs and urine did not
      differ among the three groups studied. JC virus type 2 was detected only in
      progressive multifocal leukoencephalopathy patients, and in particular in 52.4%
      of their CSF samples. Moreover, in the CSF of 19.0% of the progressive multifocal
      leukoencephalopathy cases, dual infection with both JC virus types 1 and 2 was
      found. The data obtained in this study indicate that the unexpected involvement
      of JC virus type 2, a strain not common in Italy, and the high frequency of dual
      infection with both JC virus types 1 and 2 in progressive multifocal
      leukoencephalopathy CSF, can be indications of risk factors for progressive
      multifocal leukoencephalopathy development.

PMID- 11519481
TI  - Infection of human NT2 cells and differentiated NT-neurons with herpes simplex
      virus and replication-incompetent herpes simplex virus vectors.
AB  - The human embryonal carcinoma cell line NT2 differentiates irreversibly into
      postmitotic neuron-like cells following treatment with retinoic acid. These
      differentiated NT-neurons resemble central nervous system (CNS) neurons and are
      characterized by development of dendrites and axons and the expression of neuron
      specific markers. Because of their unique biological characteristics, NT-neurons
      were investigated for their utility as a system for studying the replication of
      herpes simplex virus (HSV) in the neuron and for evaluating characteristics of
      HSV vectors designed for gene delivery to the neuron. Virus replication in
      differentiated NT-neurons was significantly reduced and delayed relative to
      replication in undifferentiated NT2 cells. Replication of thymidine-kinase (tk)
      deficient HSV was further impaired in NT-neurons, reflecting the behavior of tk
      negative virus in primary neurons in vitro and ganglia in vivo. Furthermore,
      replication-incompetent HSV vectors were capable of infecting NT-neurons,
      expressing a foreign gene, and persisting in a recoverable state for at least 2
      weeks following delivery. These results suggest that differentiated NT-neurons
      can provide a continuous source of human, post-mitotic neurons-like cells for the
      study of HSV biology and HSV vector development.

PMID- 11519482
TI  - HIV-1 Nef co-localizes with the astrocyte-specific cytoskeleton protein GFAP in
      persistently nef-expressing human astrocytes.
AB  - In T-cells HIV-1 Nef exerts various functions and interacts with actin. In
      astrocytes interaction of Nef with cellular proteins is poorly understood.
      Therefore, human astrocytic cell clones stably transfected with nef-genes derived
      from HIV-1 Bru and its myristoylation-defective TH-variant were investigated by
      confocal laser scanning microscopy for expression of Nef and cytoskeleton
      proteins actin and GFAP, a marker for activated astrocytes. Myristoylated Nef was
      detected in cytoplasm, Golgi and plasmamembrane, while non-myristoylated Nef was
      exclusively cytoplasmic. Nef co-localised with GFAP in the perinuclear region of
      astrocytes. In contrast, Nef did not interact with actin filaments in human
      astrocytes. Nef/GFAP interaction could contribute to changes in morphology and
      activation state of astrocytes shown previously which are both critical for
      development of astrogliosis in HIV-1 infected brain.

PMID- 11519483
TI  - Quinolinic acid is produced by macrophages stimulated by platelet activating
      factor, Nef and Tat.
AB  - Activated macrophages produce quinolinic acid (QUIN), a neurotoxin, in several
      inflammatory brain diseases including AIDS dementia complex. We hypothesized that
      IL1-beta, IL6, transforming growth factor (TGF-beta2 and platelet activating
      factor could increase macrophage QUIN production. And that the HIV-1 proteins
      Nef, Tat and gp41 may also increase synthesis of QUIN by macrophages. At 72 h
      there were significant increases in QUIN production in the cells stimulated with
      PAF (914 +/- 50 nM) and Nef (2781 +/- 162 nM), with somewhat less production by
      Tat stimulation (645 +/- 240 nM). The increases in QUIN production approximated
      in vitro concentrations of QUIN shown to be neurotoxic and correlated closely
      with indoleamine 2,3-dioxygenase induction. IL1-beta, IL6, TGF-beta2 and gp41
      stimulation produced no significant increase in QUIN production. These results
      suggest that some of the neurotoxicity of PAF, nef and tat may be mediated by
      QUIN.

PMID- 11519484
TI  - Localization of retrovirus in the central nervous system of a patient co-infected
      with HTLV-1 and HIV with HAM/TSP and HIV-associated dementia.
AB  - Persons co-infected with HTLV-1 and HIV are at increased risk for neurologic
      disease. These patients may develop HAM/TSP and/or HIV-associated dementia. In
      this study, we localized cells infected with retrovirus in the central nervous
      system (CNS) of a patient with both HAM/TSP and HIV-associated dementia. HTLV-1
      was localized to astrocytes and HIV to macrophage/microglia. There was no co
      infection of a single cell phenotype in this patient. These data suggest that
      mechanisms other than co-infection of the same CNS cell may play a role in the
      development of neurologic disease in patients dual infected with HTLV-1 and HIV.

PMID- 11519485
TI  - Acceleration of HIV dementia with methamphetamine and cocaine.
AB  - We report a patient with rapidly accelerating HIV dementia accompanied by
      seizures and an unusual movement disorder despite highly potent antiretroviral
      therapy. This clinical constellation was associated with the non-parenteral use
      of methamphetamine and cocaine. Fractional enhancement time on post contrast
      magnetic resonance imaging studies revealed a progressive breakdown of the blood
      brain barrier particularly in the basal ganglia. The movement disorder but not
      the dementia responded to a combination of dopamine replacement and
      anticholinergic therapy. While the movement disorder may have been unmasked by
      concomitant anticonvulsant therapy, we suggest in this instance, that prior drug
      abuse synergized with HIV to cause a domino effect on cerebral function. Careful
      attention and analysis to histories of remote non-injecting drug abuse may help
      substantiate our hypothesis.

PMID- 11519486
TI  - Adenovirus vector-directed expression of the neurotrophin-3 receptor (TrkC) in
      mouse astrocytes.
AB  - In the present article we report the generation of a neurovirological reagent, an
      adenovirus vector that efficiently delivers the gene for the Neurotrophin-3 (NT
      3) receptor, TrkC. Using this AdTrkC vector, we examined the induction of the
      expression of the above neurotrophin receptor in pure cultures of mouse
      astrocytes, a glial cell type that does not constitutively express this gene.
      Infection of astrocytes at an optimal dose of 100-200 plaque forming units
      (p.f.u.) per cell, induced expression of specific mRNA, as demonstrated by RT-PCR
      and Northern blot. This mRNA was translated to produce a mean of 20,157
      biologically active receptor molecules per astrocyte with a Kd of 4.1 x 10(-11)
      M, as demonstrated by 125I-NT-3 binding. After 2D electrophoresis, the mature
      glycoprotein and some precursors were recognised by antibodies raised against the
      carboxy-terminal peptide of Trk. Binding of the ligand induced
      autophosphorylation ofTrkC and 3H-thymidine incorporation in transduced cells.
      These results demonstrate that our AdTrkC vector efficiently mediates the
      expression of high-levels of biologically active NT-3 receptors.

PMID- 11519488
TI  - Abstracts from the 2nd Congress Deutsche Parkinson-Gesellschaft e. V. Bochum,
      March 7-10, 2001.

PMID- 11519487
TI  - Lack of association between HSV-1 DNA in the brain, Alzheimer's disease and
      apolipoprotein E4.

PMID- 11519489
TI  - [Proceedings of the 93rd Annual Congress of the Swiss Society of Ophthalmology.
      Bern, 13-16 September 2000].

PMID- 11519490
TI  - Measuring quality of life.

PMID- 11519491
TI  - Abstracts of the 5th International Congress on Cerebral Palsy. Bled, Slovenia, 7
      10 June 2001.

PMID- 11519492
TI  - Proceedings of the 10th International Symposium on Pollutant Responses in Marine
      Organisms (PRIMO 10). Williamsburg, Virginia, USA. 25-29 April 1999.

PMID- 11519493
TI  - Large decline reported in New York City hospital inpatient census.

PMID- 11519494
TI  - Direct observation for tuberculosis treatment.

PMID- 11519495
TI  - From the Centers for Disease Control and Prevention. Two fatal cases of
      adenovirus-related illness in previously healthy young adults--Illinois, 2000.

PMID- 11519496
TI  - From the Centers for Disease Control and Prevention. Malaria deaths following
      inappropriate malaria chemoprophylaxis--United States, 2001.

PMID- 11519498
TI  - From the Centers for Disease Control and Prevention. Pulmonary hemorrhage in
      infants.

PMID- 11519497
TI  - From the Centers for Disease Control and Prevention. Evaluation of a regional
      pilot program to prevent mother-infant HIV transmission--Thailand, 1998-2000.

PMID- 11519499
TI  - JAMA patient page. Heart pacemakers.

PMID- 11519500
TI  - ACOG Committee Opinion. Committee on Ethics. Commercial enterprises in medical
      practice: Selling and promoting products.

PMID- 11519501
TI  - Characteristics of patients with uncontrolled hypertension in the United States.
AB  - BACKGROUND: Treatment of hypertension is one of the most common clinical
      responsibilities of U.S. physicians, yet only one fourth of patients with
      hypertension have their blood pressure adequately controlled. METHODS: We
      analyzed data from the third National Health and Nutrition Examination Survey to
      assess the role of access to and use of health care in the control of
      hypertension. We assessed demographic characteristics, clinical data, health
      insurance status, and awareness and treatment of hypertension in subjects with
      hypertension (defined as a blood pressure of at least 140/90 mm Hg or the use of
      antihypertensive medication) and subjects without hypertension. RESULTS: The
      study sample consisted of 16,095 adults who were at least 25 years old and for
      whom blood-pressure values were known. We estimated that 27 percent of the
      population had hypertension, but only 23 percent of those with hypertension were
      taking medications that controlled their condition. Among subjects with untreated
      or uncontrolled hypertension, the pattern was an elevation in the systolic blood
      pressure with a diastolic pressure of less than 90 mm Hg. The great majority had
      health insurance. Independent predictors of a lack of awareness of hypertension
      were an age of at least 65 years, male sex, non-Hispanic black race, and not
      having visited a physician within the preceding 12 months. The same variables,
      except for non-Hispanic black race, were independently associated with poor
      control of hypertension among those who were aware of their condition. An age of
      at least 65 years accounted for the greatest proportion of the attributable risk
      of the lack of awareness of hypertension and the lack of control of hypertension
      among those who were aware of their condition. CONCLUSIONS: Most cases of
      uncontrolled hypertension in the United States consist of isolated, mild systolic
      hypertension in older adults, most of whom have access to health care and
      relatively frequent contact with physicians.

PMID- 11519502
TI  - Failure of metronidazole to prevent preterm delivery among pregnant women with
      asymptomatic Trichomonas vaginalis infection.
AB  - BACKGROUND: Infection with Trichomonas vaginalis during pregnancy has been
      associated with preterm delivery. It is uncertain whether treatment of
      asymptomatic trichomoniasis in pregnant women reduces the occurrence of preterm
      delivery. METHODS: We screened pregnant women for trichomoniasis by culture of
      vaginal secretions. We randomly assigned 617 women with asymptomatic
      trichomoniasis who were 16 to 23 weeks pregnant to receive two 2-g doses of
      metronidazole (320 women) or placebo (297 women) 48 hours apart. We treated women
      again with the same two-dose regimen at 24 to 29 weeks of gestation. The primary
      outcome was delivery before 37 weeks of gestation. RESULTS: Between randomization
      and follow-up, trichomoniasis resolved in 249 of 269 women for whom follow-up
      cultures were available in the metronidazole group (92.6 percent) and 92 of 260
      women with follow-up cultures in the placebo group (35.4 percent). Data on the
      time and characteristics of delivery were available for 315 women in the
      metronidazole group and 289 women in the placebo group. Delivery occurred before
      37 weeks of gestation in 60 women in the metronidazole group (19.0 percent) and
      31 women in the placebo group (10.7 percent) (relative risk, 1.8; 95 percent
      confidence interval, 1.2 to 2.7; P=0.004). The difference was attributable
      primarily to an increase in preterm delivery resulting from spontaneous preterm
      labor (10.2 percent vs. 3.5 percent; relative risk, 3.0; 95 percent confidence
      interval, 1.5 to 5.9). CONCLUSIONS: Treatment of pregnant women with asymptomatic
      trichomoniasis does not prevent preterm delivery. Routine screening and treatment
      of asymptomatic pregnant women for this condition cannot be recommended.

PMID- 11519503
TI  - Effects of clopidogrel in addition to aspirin in patients with acute coronary
      syndromes without ST-segment elevation.
AB  - BACKGROUND: Despite current treatments, patients who have acute coronary
      syndromes without ST-segment elevation have high rates of major vascular events.
      We evaluated the efficacy and safety of the antiplatelet agent clopidogrel when
      given with aspirin in such patients. METHODS: We randomly assigned 12,562
      patients who had presented within 24 hours after the onset of symptoms to receive
      clopidogrel (300 mg immediately, followed by 75 mg once daily) (6259 patients) or
      placebo (6303 patients) in addition to aspirin for 3 to 12 months. RESULTS: The
      first primary outcome--a composite of death from cardiovascular causes, nonfatal
      myocardial infarction, or stroke--occurred in 9.3 percent of the patients in the
      clopidogrel group and 11.4 percent of the patients in the placebo group (relative
      risk with clopidogrel as compared with placebo, 0.80; 95 percent confidence
      interval, 0.72 to 0.90; P<0.001). The second primary outcome--the first primary
      outcome or refractory ischemia--occurred in 16.5 percent of the patients in the
      clopidogrel group and 18.8 percent of the patients in the placebo group (relative
      risk, 0.86; 95 percent confidence interval, 0.79 to 0.94; P<0.001). The
      percentages of patients with in-hospital refractory or severe ischemia, heart
      failure, and revascularization procedures were also significantly lower with
      clopidogrel. There were significantly more patients with major bleeding in the
      clopidogrel group than in the placebo group (3.7 percent vs. 2.7 percent;
      relative risk, 1.38; P=0.001), but there were not significantly more patients
      with episodes of life-threatening bleeding (2.2 percent [corrected] vs. 1.8
      percent; P=0.13) or hemorrhagic strokes (0.1 percent vs. 0.1 percent).
      CONCLUSIONS: The antiplatelet agent clopidogrel has beneficial effects in
      patients with acute coronary syndromes without ST-segment elevation. However, the
      risk of major bleeding is increased among patients treated with clopidogrel.

PMID- 11519504
TI  - Images in clinical medicine. Hydatidiform mole.

PMID- 11519505
TI  - The Master Settlement Agreement with the tobacco industry and cigarette
      advertising in magazines.
AB  - BACKGROUND: In 1998, the attorneys general of 46 states signed a Master
      Settlement Agreement with the four largest tobacco companies in the United
      States. The agreement prohibits tobacco advertising that targets people younger
      than 18 years of age. METHODS: We analyzed the trends in expenditures for
      advertising for 15 specific brands of cigarettes and the exposure of young people
      to cigarette advertising in 38 magazines between 1995 and 2000. We defined
      cigarette brands as "youth" brands if they were smoked by more than 5 percent of
      the smokers in the 8th, 10th, and 12th grades in 1998; all others were considered
      to be "adult" brands. We classified magazines as youth-oriented magazines if at
      least 15 percent of their readers or at least 2 million of their readers were 12
      to 17 years old. "Reach," a standard measure of exposure to advertising, was
      defined as the number of young persons who read at least one issue of a magazine
      containing an advertisement for a particular brand of cigarette during a given
      year. RESULTS: In 2000 dollars, the overall advertising expenditures for the 15
      brands of cigarettes in the 38 magazines were $238.2 million in 1995, $219.3
      million in 1998, $291.1 million in 1999, and $216.9 million in 2000. Expenditures
      for youth brands in youth-oriented magazines were $56.4 million in 1995, $58.5
      million in 1998, $67.4 million in 1999, and $59.6 million in 2000. Expenditures
      for adult brands in youth-oriented magazines were $72.2 million, $82.3 million,
      $108.6 million, and $67.6 million, respectively. In 2000, magazine advertisements
      for youth brands of cigarettes reached more than 80 percent of young people in
      the United States an average of 17 times each. CONCLUSIONS: The Master Settlement
      Agreement with the tobacco industry appears to have had little effect on
      cigarette advertising in magazines and on the exposure of young people to these
      advertisements.

PMID- 11519506
TI  - Clinical practice. Subclinical hyperthyroidism.

PMID- 11519507
TI  - Idiopathic pulmonary fibrosis.
AB  - Idiopathic pulmonary fibrosis is a rapidly progressive illness of unknown cause
      characterized by sequential acute lung injury with subsequent scarring and end
      stage lung disease. Treatment at present remains largely supportive, with
      evidence that patients' satisfaction and survival may be improved by referral to
      centers specializing in the evaluation of interstitial lung diseases. Although no
      drug therapy has clearly been demonstrated to benefit patients with idiopathic
      pulmonary fibrosis, a number of novel investigational agents hold promise for
      future study. Given the poor prognosis associated with idiopathic pulmonary
      fibrosis, patients should be referred to regional centers of expertise for
      enrollment in therapeutic clinical trials or for lung transplantation.

PMID- 11519509
TI  - Control of hypertension--an important national priority.

PMID- 11519508
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 25-2001. A 71-year-old man with gastric ulcers and ileocecal
      thickening eight years after renal transplantation.

PMID- 11519510
TI  - Beyond the tobacco settlement.

PMID- 11519511
TI  - Risks to health care workers in developing countries.

PMID- 11519512
TI  - Neurocognitive function after coronary-artery bypass surgery.

PMID- 11519513
TI  - Neurocognitive function after coronary-artery bypass surgery.

PMID- 11519514
TI  - Neurocognitive function after coronary-artery bypass surgery.

PMID- 11519515
TI  - Neurocognitive function after coronary-artery bypass surgery.

PMID- 11519516
TI  - Neurocognitive function after coronary-artery bypass surgery.

PMID- 11519517
TI  - A Salmonella typhi Vi conjugate vaccine.

PMID- 11519518
TI  - Cardiac resuscitation.

PMID- 11519519
TI  - Cardiac resuscitation.

PMID- 11519520
TI  - Cardiac resuscitation.

PMID- 11519522
TI  - Tropheryma whipplei circulating in blood monocytes.

PMID- 11519521
TI  - Case 13-2001: genetic testing in pheochromocytoma.

PMID- 11519523
TI  - Surgical-wound infection with Pasteurella multocida from pet dogs.

PMID- 11519524
TI  - DNA hybridization arrays: a powerful technology for nutritional and obesity
      research.

PMID- 11519525
TI  - Parathyroid hormone secretion in low calcium intake smokers.

PMID- 11519526
TI  - Cardiovascular endocrinology: into the new millennium.

PMID- 11519527
TI  - [Comparison of body fat using anthropometry bioelectrical impedance and DEXA in
      elderly women].
AB  - Verify correspondence and compare percentage body fat (%BF) estimates by skinfold
      thickness (SKT), bioelectrical impedance analysis (BIA) and DEXA. Twenty
      voluntaries women (aged 62-79 yr) were assessed. The body fat was estimated using
      two different equations of SKT(Jackson (19); Durning and Womersley, (20)), BIA
      using two-predictions formulas (23) and DEXA. To compare mean values of %BF was
      used analysis of variance for repeated measures (ANOVA--Bonferroni), the
      correlation of the inter-method was verified by Pearson correlation coefficients
      (r), and correspondence between prediction formulas was tested by using the
      approach by Bland and Altman (25). The %BF assessed by BIA (23) shown poor
      correlation (r < 0.5) with two SKT equations. The %BF ranged from 31.5 +/- 5.5 to
      41.2 +/- 6.1 (mean +/- SD) for Jackson (19) e DEXA, respectively. The analysis of
      variance shown no significant differences (p > 0.05) between methods and/or
      equations by BIA (RJL-CompCorp) vs. DC-Jackson (19). There were observed
      significant differences (p < 0.001) between all comparisons. The correspondence
      between RJL-CompCorp vs. Deurenberg (23) was good and the same was observed for
      DEXA vs. Durning and Womersley (20). Although the methods and/or equations used
      in this study have been commonly utilized to estimate BF in elderly subjects,
      they neither must be used as a standard method. Each method has limitations and
      the comparison can be useful for interpretation of results.

PMID- 11519528
TI  - Microbial fitness and genome dynamics.

PMID- 11519529
TI  - Protein conjugate vaccines--how much is enough?

PMID- 11519530
TI  - The Campylobacter conundrum.

PMID- 11519532
TI  - Society for the Study of Inborn Errors of Metabolism 39th annual symposium.
      Prague, Czech Republic, 4-7 September 2001. Abstracts.

PMID- 11519531
TI  - Effect of hyoscine N-butylbromide on gastroesophageal reflux in normal subjects
      and patients with gastroesophageal reflux disease.
AB  - OBJECTIVES: Recent studies have shown that atropine reduces gastroesophageal
      reflux in normal subjects and patients with gastroesophageal reflux. The aim of
      the study has been to assess the effects of an atropine derivative, hyoscine N
      butylbromide in normal subjects and patients with gastroesophageal reflux disease
      by recording esophageal and gastric pH-metry for a 24-h period. METHODS: Ten
      normal subjects and 10 patients with gastroesophageal reflux disease were
      evaluated. PH-metry was performed using two glass pH flexible probes with distal
      incorporated electrodes. The two catheters were introduced nasally under
      fluoroscopy. One probe was positioned in the gastric body; the other was placed 5
      cm above the lower esophageal sphincter which had been evaluated manometrically
      before the study. Recording lasted without interruption for 48 h. Patients and
      normal subjects were assigned to receive hyoscine N-butylbromide (10 mg p.o.
      t.i.d.) for 24 h followed by a placebo for another 24 h or vice versa in a random
      manner. The pH was analyzed for a total number of acid refluxes and percentage of
      the period with pH <4 in the esophagus and the mean gastric pH in 24 h, before
      and after treatment with hyoscine N-butylbromide. RESULTS: The number of reflux
      episodes was significantly greater with hyoscine N-butylbromide in comparison
      with a placebo in patients with gastroesophageal reflux disease and normal
      subjects (p < 0.02). The percentage of time with pH <4, was also significantly
      greater in patients with gastroesophageal reflux disease and in controls (p <
      0.05). The mean 24-h gastric pH after hyoscine N-butylbromide was not different
      from placebo in gastroesophageal reflux disease and controls. CONCLUSIONS:
      Hyoscine N-butylbromide, an anticholinergic agent, increases the total number of
      esophageal acid refluxes in patients with gastroesophageal reflux disease and in
      controls, therefore it is not recommended in the treatment of gastroesophageal
      reflux disease.

PMID- 11519533
TI  - Abstracts for the 10th International Conference on Bioinorganic Chemistry.
      Florence, Italy, August 26-31, 2001.

PMID- 11519534
TI  - Missouri State Medical Association 2001-2002 membership directory.

PMID- 11519535
TI  - XXth International Conference on Yeast Genetics and Molecular Biology. Prague,
      Czech Republic, August 26-31, 2001. Abstracts.

PMID- 11519536
TI  - Interpretation of Doppler signals.
AB  - Combining color and spectral data, Doppler signal provides physiologic
      information about arterial and venous hemodynamics and anatomic information about
      vessel walls and diameter. Adequate sampling of Doppler signal is required to
      avoid pitfalls in interpreting spectral changes or color images. The level of
      information contained in spectral waveforms is high, compared with color display
      in terms of velocity profile alterations, as in stenoses, and cyclic changes of
      systolo-diastolic velocities. Therefore, integration of information from both
      types of Doppler signal representations is mandatory in clinical practice.

PMID- 11519537
TI  - Artefacts in sonography and Doppler.
AB  - A working knowledge of the most common artefacts in sonography is essential in
      order to avoid not only misdiagnosis of artefacts as pathology but also failure
      to detect pathology "in disguise". The basic artefacts affecting all sonography
      and some of the ones particular to Doppler and contrast ultrasound are discussed.

PMID- 11519538
TI  - Ultrasound contrast agents: properties, principles of action, tolerance, and
      artifacts.
AB  - The concept of contrast imaging was introduced to ultrasound almost 30 years ago.
      The development of ultrasound contrast agents (USCAs), initially slowed by
      technical limitations, has become more dynamic during the past decade. The ideal
      USCA should be non-toxic, injectable intravenously, capable of crossing the
      pulmonary capillary bed after a peripheral injection, and stable enough to
      achieve enhancement for the duration of the examination. While satisfying cost
      benefit requirements, it should provide not only Doppler but also gray-scale
      enhancement. Already, Doppler examinations are improved by using USCAs when
      studying deep and small vessels, vessels with low or slow flow, or vessels with a
      non-optimal insonation angle. Ultrasound contrast agents also enhance detection
      of flow within abnormal vessels, including tumor vascularization and stenotic
      vessels, and provide better delineation of ischemic areas. Research is focusing
      on the development of specific contrast imaging sequences that allow detection of
      tissue enhancement similar to that obtained with CT or MRI. These sequences take
      advantage of the nonlinear behavior of the microbubbles within the ultrasound
      field, bringing real-time perfusion imaging for liver, kidney, and the myocardium
      into reach. New objectives include targeted agents that could further widen USCA
      applications to specific delivery of active drugs such as anticoagulants or
      cytotoxic compounds. The combination of new generations of USCAs and new
      ultrasound image sequences appears to be very promising and currently represents
      a significant part of ultrasound research.

PMID- 11519539
TI  - Ultrasound contrast agents: clinical applications.
AB  - Ultrasound contrast agents (USCA) for intravenous injections are usually gas
      filled microbubbles with a mean diameter less than that of a red blood corpuscle.
      There are only a few products on the market at the time of this writing, but
      several companies have various agents under development. This paper covers both
      established USCA on the market, and some new agents under clinical evaluation.
      The potential of improving ultrasound imaging using USCA depends on several
      factors. These factors include the pharmacokinetic and pharmacodynamic properties
      of the products, which determine the effects they have on various ultrasound
      imaging techniques. Furthermore, the proper clinical application of the agents
      requires a combination of technical and medical knowledge by the examiner,
      dedicated equipment, a disease that can be diagnosed or characterised by
      ultrasound and USCA, and a cooperative patient. Taking into account these
      factors, USCA can be used for improving the detection, characterisation and
      follow-up of diseases of several vascular beds and parenchymal organs from head
      to foot.

PMID- 11519540
TI  - Quantification of blood flow.
AB  - Traditionally, Doppler ultrasound has been used to estimate blood flow as the
      mean velocity multiplied by the vessel area, but this is subject to significant
      errors and may be difficult to perform accurately. Microbubbles, developed as
      contrast agents for ultrasound, were initially envisaged as useful for increasing
      the intensity of echoes and thus rescuing Doppler studies that were technical
      failures because of attenuated signals or very slow flow. However, they can act
      as tracers and, by analogy with isotope techniques, can be used to measure blood
      flow with transit-time methods which exploit both arterial and venous time
      intensity data. An acceptable compromise is to acquire both a tissue intensity
      curve and one from the feeding artery. The transit of microbubbles across an
      organ or tissue can be used to estimate haemodynamic alterations, e.g. the
      arterialisation of the supply to the liver in malignancies and cirrhosis and the
      delayed arterio-venous transit in the transplant kidney during rejection. The
      fragility of microbubbles can be turned to advantage by being exploited to create
      a negative bolus by exposing a tissue slice to a high power beam. The rate of
      refilling of this slice by circulating microbubbles can then be followed with a
      low-intensity monitoring beam and the resulting rising exponential curve analysed
      to extract indices of both the reperfusion rate (the slope) and the fractional
      vascular volume (the asymptote). The product of these is a measure of true tissue
      perfusion.

PMID- 11519541
TI  - Detection of pulmonary nodules at spiral CT: comparison of maximum intensity
      projection sliding slabs and single-image reporting.
AB  - The aim of this study was to compare numbers of pulmonary nodules detected with
      maximum intensity projections using a slab thickness of 15 mm (MIP 15) and 30 mm
      (MIP 30) with single image (SI) presentation of chest CT scans. Two readers
      reviewed MIP 15, MIP 30, and SI presentations of 10-mm (n = 8) and 5-mm
      collimation (n = 10) helical CT scans and recorded size, location, and diagnostic
      confidence (definite, probable) of pulmonary nodules. Readers 1 and 2 recorded
      more nodules with MIP 15 than with SI: 10-mm collimation, 77/64 and 60/56; 5-mm
      collimation, 64/60 and 40/36; and more "definite" nodules (10-mm collimation:
      68/57 and 51/42; 5-mm collimation: 43/36 and 34/30). MIP 15 also detected more
      nodules than MIP 30 at 10-mm collimation: 77/72 and 60/50; with no major
      differences at 5-mm collimation: 64/66 and 40/38; and more "definite" nodules (10
      mm collimation: 68/58 and 51/36; 5-mm collimation: 43/39 and 34/29). There were
      only minor differences between SI and MIP 30. Reading time and image number per
      study were reduced with MIP presentations by a factor of 1.4-5.3. There were no
      significant differences in the number of nodules detected with SI, MIP 15, and
      MIP 30, but MIP presentation reduced reporting time and filming cost when
      compared with SI reporting. For detection of nodules MIP 15 was slightly superior
      to MIP 30.

PMID- 11519542
TI  - Deliberate, repeated self-administration of metallic mercury injection: case
      report and review of the literature.
AB  - Self-administration of metallic mercury through the intravenous route is rare.
      This event has been reported in psychiatric patients and in suicide attempts. We
      report a case of successive intravenous self-injections of mercury demonstrated
      by plain film radiographs and CT scans of the thorax and abdomen.

PMID- 11519543
TI  - Contrast-enhanced three-dimensional MR angiography of the thoracic aorta:
      experiences after 118 examinations with a standard dose contrast administration
      and different injection protocols.
AB  - The aim of this study was to test three injection protocols for contrast-enhanced
      magnetic resonance angiography (MRA) of the thoracic aorta with a standard-dose
      application. Ninety-three patients with a total of 118 examinations underwent MRA
      of the thoracic aorta at 1.5 T. There were three injection protocols: in 24
      cases, no test bolus was performed and contrast was injected manually; in 14
      cases, contrast was injected manually after a test bolus; and in 80 cases, a MR
      compatible injector was used after a timing examination. All patients received 20
      ml of Gd-DTPA. Quantitative signal-to-noise (SNR) measurements were obtained at
      different locations in the thoracic aorta, the pulmonary arteries, and the
      superior vena cava. Two readers in conference retrospectively evaluated each
      examination with respect to overall image quality and quality of bolus timing.
      Bolus timing was considered optimal in 70 cases, and either too early or too late
      in 11 cases. In 37 examinations the bolus was broadened. The SNR measurements of
      the thoracic aorta revealed that examinations after bolus testing were
      significantly superior to examinations without a test bolus (p < 0.001). Signal
      intensity ratios of the aorta and the pulmonary trunk were significantly higher
      in examinations with an optimal contrast timing (p < 0.001). Magnetic resonance
      angiograms of the thoracic aorta with a timing run are significantly superior to
      non-timed examinations with respect to image quality and SNRs. The administration
      of 20 ml of Gd-DTPA is sufficient for adult patients.

PMID- 11519544
TI  - Excimer laser-assisted recanalisation of femoral arterial stenosis or occlusion
      caused by the use of Angio-Seal.
AB  - The aim of this study was to demonstrate the effect of excimer laser and balloon
      angioplasty of femoral artery stenosis and occlusion after use of a haemostatic
      puncture closure device. A haemostatic puncture closure device (Angio-Seal) was
      used in 6000 patients after diagnostic or therapeutic artery catheterisation. In
      34 of those patients symptoms of peripheral artery disease occurred. Sixteen of
      those 34 cases were transferred to our clinic for excimer laser angioplasty. All
      16 patients presented with symptoms of acute peripheral artery disease within 1
      14 days: superficial femoral artery (SFA) occlusions (4 cases); superficial
      femoral artery stenosis (3 cases); high-grade stenosis of the common femoral
      artery (CFA; 3 cases); high-grade stenosis of CFA; SFA and profund femoral artery
      (PFA; 3 cases); and occlusions of CFA, SFA and PFA (3 cases). Before any
      procedure was performed, informed consent was given by the patient, which
      included the use of the Angio-Seal closure device. Every patient who had to
      undergo recanalisation procedures gave additional informed consent which
      especially included the usage of the excimer laser for recanalisation. A
      measurement of the walking distance, ankle-brachial systolic pressure index (ABI)
      and diagnostic angiography was performed in 13 cases before and immediate after
      as well as 3 and 6 months after therapeutic percutaneous transluminal laser
      angioplasty followed by balloon angioplasty (PTLA/PTA). In 3 patients the risks
      of PTLA/PTA was considered too high; those patients underwent surgical repair.
      Angiographic and clinical improvement was achieved in 13 of 13 patients. The mean
      walking distance increased from 81 to > 400 m. The average ankle-brachial
      systolic pressure index (ABI) increased from 0.47 to 0.84. One patient developed
      a dissection of the SFA, and in 1 case a peripheral embolisation was seen. The
      PTLA/PTA technique is a successful therapeutic option for patients with femoral
      artery occlusion or high-grade stenosis after Angio-Seal application.

PMID- 11519545
TI  - Rupture of an aneurysm of the coronary sinus of Valsalva: diagnosis by helical CT
      angiography.
AB  - A 75-year-old man presented with a 5-day history of upper chest discomfort. On
      auscultation, there was a systolic murmur in the left parasternal area that
      radiated to the apex. Electrocardiography showed flat T waves in the anterior
      precordial leads. Chest X ray revealed mediastinal enlargement. Transthoracic
      echocardiography showed a dilated proximal ascending aorta with moderate aortic
      regurgitation. A contrast-enhanced helical CT scan, performed to eliminate an
      aortic dissection, showed a ruptured left coronary sinus of Valsalva aneurysm,
      confirmed at surgery. This case highlights the fact that helical CT, in patients
      with suspected aortic dissection, may reveal other pathology that accounts for
      the clinical presentation.

PMID- 11519546
TI  - Focal liver lesions: MR imaging-pathologic correlation.
AB  - Magnetic resonance signal intensity of focal liver lesions is affected by
      numerous pathologic factors. Lesion histologic features, such as cellularity,
      vascularity, stromal component, and intratumoral necrosis or hemorrhage, strongly
      affect T1 and T2 relaxation times. Additionally, intracellular content of certain
      substances, such as glycogen, fat, melanin, iron, and copper, may also have a
      substantial role in determining MR signal behavior. In this review we discuss the
      correlations between MR imaging features and pathologic findings in benign and
      malignant focal liver lesions. Knowledge of imaging-pathology correlations
      greatly assist in charac terizing focal lesions. Moreover, in certain tumor
      histotypes, such as hepatocellular carcinoma, careful analysis of lesion signal
      intensity may help predict the degree of tumor differentiation.

PMID- 11519547
TI  - Correlation of MRI and CT findings with histopathology in hepatic angiomyolipoma.
AB  - Hepatic angiomyolipomas are rare and often mimic other liver tumors. The aim of
      our study was to describe the CT and MRI findings and to correlate imaging
      features with histopathology. The CT and/or MR images were available for
      retrospective analysis in seven patients. Patients had non-enhanced as well as
      enhanced CT (n = 6) or MRI (n = 4) before and after administration of Gd-DTPA (n
      = 2) or MnDPDP, a liver specific contrast agent, (n = 3). In three patients CT
      and MRI did not detect fat, and in two patients the angiomyolipomas were also
      histopathologically devoid of fat. Vascularity ranged from hypervascular (n = 4)
      with arteriovenous shunts (n = 1) to equal (n = 1) or less (n = 2) postcontrast
      enhancement compared with the normal liver parenchyma. No uptake of the liver
      specific contrast agent, MnDPDP, was observed (n = 3). Predominantly, CT and MRI
      did not include angiomyolipoma in the differential diagnosis, and the initial
      histopathological evaluation was inconclusive in more than half the cases.
      Hepatic angiomyolipomas frequently manifest as solitary well-circumscribed
      heterogeneous masses in patients with no underlying liver disease or elevation of
      serum tumor markers. If present, the demonstration of intratumoral fat is helpful
      in the diagnosis of angiomyolipoma. The final diagnosis can be obtained by
      immunohistochemistry.

PMID- 11519548
TI  - Optimization of automatic bolus tracking for timing of the arterial phase of
      helical liver CT.
AB  - The aim of this study was to optimize bolus tracking for timing of the arterial
      phase of biphasic helical liver CT and to compare optimized bolus tracking to a
      standard delay. One hundred fifty patients were examined with six protocols: 5-
      or 10-s delay after triggering at a threshold of 50 or 75 or 100 HU enhancement
      in the aorta at the origin of the celiac arteries after injection of 120 ml
      contrast material at 3 ml/s. Optimal arterial enhancement was defined as 20-30%
      of hepatic enhancement in portal venous phase. Another 50 patients were examined
      with the optimized protocol and compared to 50 gender- and age-matched patients
      who underwent a 25-s standard delay. A 10-s delay after the 75-HU threshold
      resulted in the most patients with an optimal arterial phase (p < 0.01). Thirty
      one of 75 patients examined with this protocol showed optimal early liver
      enhancement. Bolus tracking compared with standard delay revealed only a trend
      for a difference (p = 0.07). The outcome of automatic bolus tracking differs
      depending on the protocol used; however, optimal arterial phase imaging was seen
      in only 41% of patients, indicating only a trend for superior timing compared
      with a standard delay.

PMID- 11519549
TI  - Autoimmune pancreatitis associated with primary sclerosing cholangitis: MR
      imaging findings.
AB  - Autoimmune pancreatitis is a relatively rare type of chronic pancreatitis that
      may be associated with other autoimmune disorders. The imaging features of this
      entity may be misleading and suggest the presence of a malignant tumour. We
      present a case in which MR imaging allowed us to diagnose autoimmune pancreatitis
      associated with primary sclerosing cholangitis, which is another autoimmune
      related disease. Typical MR characteristics of autoimmune pancreatitis include
      focal or diffuse enlargement of the pancreas, the absence of parenchymal atrophy
      and significant dilation proximal to the site of stenosis, the absence of
      peripancreatic spread, the clear demarcation of the lesion and the presence of a
      peripancreatic rim.

PMID- 11519550
TI  - Small bowel obstruction: the role of computed tomography in its diagnosis and
      management with reference to other imaging modalities.
AB  - Small bowel obstruction is a leading cause of acute surgical admissions for
      abdominal pain. There is an increasing tendency for initial conservative
      management rather than immediate operative intervention, as a proportion of cases
      will resolve spontaneously. This has resulted in a growing reliance on
      radiological investigations to reassure the surgeon that medical therapy can be
      safely instituted. The onus therefore rests with radiologists to guide their
      surgical colleagues by correctly interpreting the plain abdominal radiograph and
      suggesting appropriate further investigation if warranted. Recently, computed
      tomography (CT) has been proposed as the test of choice to define the level and
      cause of acute small bowel obstruction and to identify complications such as
      ischaemia and perforation which will prompt surgical intervention. This review
      will discuss the utility of early CT in the diagnosis of acute small bowel
      obstruction and outline its impact on patient management.

PMID- 11519551
TI  - Activity of Crohn's disease assessed by colour Doppler ultrasound analysis of the
      affected loops.
AB  - The aim of this study was to evaluate with colour Doppler ultrasound the vascular
      changes in the wall of the loops affected by Crohn's disease, and to establish
      whether these changes reflects clinical or biochemical activity of Crohn's
      disease. Seventy-nine patients with Crohn's disease (44 with active disease and
      35 inactive patients) were studied with frequency- and amplitude-encoded duplex
      Doppler sonography. A group of 35 healthy volunteers were also included. The exam
      consisted of the search for colour signals in the walls of the loops affected by
      Crohn's disease, classifying the degree of vascularity with a simple scoring
      system into three groups: absence of colour signal (score of 0); weak or
      scattered colour signals (score of 1); and multiple colour signals or clear
      identification of vessels in the loops walls (score of 2). Doppler curves were
      obtained of the detected vessels with measurement of the resistive index (RI).
      There was a visible increase in the gut walls' vascularity in the active patients
      compared with those with inactive disease. The mean RI was statistically
      significantly lower in the gut wall vessels of the patients with active illness
      than that obtained in the inactive patients. Colour Doppler ultrasound is a
      useful tool in the assessment of activity in Crohn's disease.

PMID- 11519552
TI  - Magnesium ions and barium coating of colonic mucosa: is it a simple question of
      viscosity?
AB  - The aim of the present study was to verify whether magnesium-induced increase of
      barium coating of the colonic mucosa is specifically due to the increase of
      barium suspension viscosity. One hundred sixty-one patients scheduled for double
      contrast barium enema (DCBE) were randomised in one group of 23 patients (control
      group, CG), and three groups of 23 pairs (G1, G2 and G3), i.e. 138 patients. The
      DCBE was performed with standard technique using a barium suspension with dynamic
      viscosity of 280 cPs (CG), or with viscosity increased to 320 cPs (G1), 2500 cPs
      (G2) or 3200 cPs (G3), by extemporaneous addition of MgSO4 1, 2 or 3 g in one
      member of the pair, Na2SO4 1, 4.2 or 8 g in the other one. Three radiologists
      evaluated on an ordinal scale mucosal coating and free fluid. In all magnesium
      subgroups barium coating was better than in CG (p < 0.008), the highest value
      being obtained in G2. No difference was observed as regards free fluid. Inside
      paired groups, mucosal coating was more effective in magnesium than in sodium
      members (p < 0.0002). Viscosity of barium suspension being equal inside each
      group, this effect must be attributed to magnesium-specific interactions with
      additives of the barium suspension inducing events other than viscosity changes.

PMID- 11519553
TI  - The accordion sign at CT: report of a case of Crohn's disease with diffuse
      colonic involvement.
AB  - The accordion sign is a finding that could be seen on CT scans of the abdomen in
      patients who have received oral contrast material. Initially, it was described as
      a sign specific of Clostridium difficile colitis, but it is also reported to
      represent a sign of diffuse colonic edema of several other etiologies. We report
      a case of a patient with Crohn's pancolitis whose abdominal CT scan presented the
      accordion sign throughout the entire large bowel together with signs of Crohn's
      disease of the small bowel.

PMID- 11519554
TI  - How accurate is helical CT volumetric assessment in renal tumors?
AB  - The aim of this study was to evaluate the accuracy of tumor size measurement on
      CT studies of renal tumors. Sixteen patients with tumors of the kidneys were
      imaged by helical CT prior to surgery. Assessment of tumor volume was made by two
      radiologists on the CT images with the summation of area method, then compared
      with the resected specimen water displacement volume. Intra- and interobserver
      agreement for CT measurements were also assessed. There were substantial
      differences between the CT volume measurement compared with the tumor post
      operative volume (mean of differences 30.05+/-91.6, 95%CI: 31.45-91.55). The
      inter- and intraobservation agreements for tumor measurement by CT was found to
      be satisfactory (ANOVA: p < 0.0001; t-test: p < 0.05). The CT volumetric
      measurement by area summation is a method with good inter- and intraexamination
      reproducibility but not an accurate technique for tumor volume assessment.

PMID- 11519555
TI  - Three-dimensional dynamic MR hysterosalpingography: a preliminary report.
AB  - The aim of this study was to evaluate the feasibility of three-dimensional
      dynamic MR hysterosalpingography (3D MR HSG) for visualization of the cavum uteri
      and demonstration of bilateral fallopian tube patency as an alternative to
      conventional hysterosalpingography. Five infertile female patients underwent 3D
      dynamic MR HSG prior to conventional hysterosalpingography. The MR protocol
      consisted of axial T1-weighted spin-echo (SE), axial/coronal T2-weighted fast SE
      (FSE), and 3D MR angiography sequences before, during, and after injection of a
      diluted gadolinium solution into the cavum uteri via a balloon catheter.
      Positioning of the catheter was feasible in all patients. In one patient the
      catheter slipped out during MRI and in one patient the catheter was placed far in
      the cavum uteri. In three patients catheter position was optimal at the level of
      the cervical canal. Evaluation of pelvic anatomy, myometrium, and ovaries was
      possible in all patients on the basis of T1-weighted SE and T2-weighted FSE.
      Three-dimensional visualization of the dilated cavum uteri was possible in four
      patients. In these four patients 3D MR HSG also proved bilateral fallopian tube
      patency which was confirmed in each patient by conventional
      hysterosalpingography. Three-dimensional MR HSG is feasible and further research
      should be done to determine if this technique can evolve into an alternative
      technique to conventional hysterosalpingography with the advantages of no
      radiation and additional visualization of the uterus wall and ovaries.

PMID- 11519556
TI  - MR imaging of brown tumour with fluid-fluid levels: a report of three cases.
AB  - Fluid-fluid levels on CT and MR imaging are a typical feature of aneurysmal bone
      cysts but have also been reported in many other osseous lesions containing
      haemorrhage. We report fluid-fluid levels in four brown tumour in three patients
      with primary hyperparathyroidism in which the initial radiological diagnosis was
      thought to be a bone tumour. To the authors' knowledge, this is the first time
      that association has been reported in the international literature.

PMID- 11519557
TI  - Reconstructed anterior cruciate ligaments using patellar tendon ligament grafts:
      diagnostic value of contrast-enhanced MRI in a 2-year follow-up regimen.
AB  - We analyzed prospectively the diagnostic efficacy of contrast-enhanced MRI
      following anterior cruciate neoligament (ACL) reconstruction. One hundred fifty
      six MR examinations were performed 2, 12, 52, 76, and 104 weeks post-operatively
      on 68 patients with ACL transplants. Sagittal, parasagittal, and coronal images
      using unenhanced T1- and T2-weighted spinecho sequences, and post-contrast images
      utilizing T1-weighted spinecho and fat-saturated sequences, were acquired.
      Results were correlated with those of the pivot shift, Lachman, and a mechanical
      test. The MR examination criteria included morphological analysis, signal
      intensity, transplant contrast enhancement, secondary signs (e.g., elongation of
      normal ligaments), and comparison with clinically standardized test results. Two
      weeks post-operatively all neoligaments showed homogeneous low signal intensity
      on T1- and T2-weighted spinecho sequences indistinguishable from that of normal
      cruciate or patellar ligaments [contrast-to-noise ratio (C/N) on T1: 1.6], with a
      9% percentile enhancement. At 12-52 weeks, signal intensity increased (C/N: 6.7),
      with a mean 50% percentile enhancement. The 1-year follow-up allowed no definite
      assessment of the neoligament's course. At 76 and 104 weeks, significant
      decrements in signal intensity (C/N: 3.0) and ligamentous percentile enhancement
      (25%) occurred. All patients tested displayed stable transplants 2 years post
      operatively. Contrast-enhanced MRI allows accurate evaluation of morphology and
      function up to 3 months postoperatively and 1-2 years following ACL
      reconstructive surgery.

PMID- 11519558
TI  - Transcatheter arterial embolization for bone metastases from hepatocellular
      carcinoma.
AB  - The objective of this study was to determine which of the following three methods
      is the most effective for the treatment of bone metastases from hepatocellular
      carcinoma (HCC): transcatheter arterial embolization (TAE); combination of TAE
      and external radiotherapy; or external radiotherapy alone. Thirty-nine metastatic
      bone lesions from HCC in 33 patients were retrospectively reviewed. Each lesion
      underwent either TAE alone (group A, n = 11), TAE followed by radiotherapy (group
      B, n = 17), or radiotherapy alone (group C, n = 11). They were evaluated on the
      following subjects: pain relief; improvement of daily activities; and
      complications. Each treatment was effective for pain relief (89-94%) and
      improvement of daily activities (73-82%). The mean time interval from the
      beginning of each treatment to the onset of initial pain relief was 4.7 days in
      group A, 4.8 days in group B, and 15 days in group C. Recurrence of the pain
      after the initial pain relief was noted in 75% in group A, 20% in group B, and
      88% in group C. Pyrexia and local pain commonly occurred after TAE. In
      conclusion, TAE is effective in relieving pain immediately and in improving the
      patients' daily activities. The combination of TAE and radiotherapy is
      recommended for permanent pain relief.

PMID- 11519559
TI  - Early MR changes in vertebral bone marrow for patients following radiotherapy.
AB  - Our study aimed to evaluate the vertebral marrow changes in patients following
      radiotherapy (RT) by measuring the T2 relaxation times before and during RT. We
      were mostly interested in evaluating early MR marrow changes during RT. Fifteen
      patients treated by RT for cervical cancer were submitted to MR examination
      before and during RT (5-23 days of RT). T2 values were calculated for irradiated
      and non-irradiated tissues (lumbar and sacral vertebral bone marrow, symphysis
      pubis marrow, and regional muscle). Fourteen patients presented increased T2
      values for irradiated vertebral bone marrow (VBM), and 3 patients showed
      increased T2 values even for non-irradiated VBM. We found T2 variations for VBM
      as early as in the fifth day of RT for an absorbed dose as small as 9 Gy.
      Calculated T2 values in irradiated and also in non-irradiated tissues prove very
      early tissue alterations.

PMID- 11519560
TI  - Diagnostic imaging of tumors of the hand and wrist.
AB  - Tumors of the hand and wrist most commonly result from dystrophic lesions and
      hamartomas. Neoplastic lesions are rare. Imaging modalities are required for
      their detection and accurate location, careful assessment of the internal
      structure and borders, evaluation of the relation with surrounding tendons,
      nerves, and vessels, and are also required for staging. A variety of imaging
      techniques, including standard radiographs, sonography, CT, and MRI, can be
      obtained. The aim of this article is to present paradigmatic images of a variety
      of expansible lesions of the hand and wrist and to describe and compare the
      diagnostic findings of different imaging techniques.

PMID- 11519561
TI  - Recurrence of a primary malignant giant cell tumour of bone 14 years after
      initial surgery.
AB  - Giant cell tumour (GCT) is usually considered a benign entity. A small fraction
      of these tumours become malignant with time, and an extremely rare fraction may
      be malignant at onset. We report herein an unusual case of primary malignant GCT
      of the bone that relapsed locally with the same histology 14 years after a simple
      surgical curettage.

PMID- 11519562
TI  - Forearm soft tissue mass caused by an accessory muscle.
AB  - We present a case of forearm soft tissue mass caused by an accessory muscle,
      distal and deep to flexor carpi ulnaris muscle. Imaging studies, mainly magnetic
      resonance and ultrasound, allow a specific diagnosis, and obviate unnecessary
      surgery. In this case, the symptoms associated with ulnar compression led to
      surgery and confirmed the preoperative diagnosis.

PMID- 11519563
TI  - Low field-low cost: can low-field magnetic resonance systems replace high-field
      magnetic resonance systems in the diagnostic assessment of multiple sclerosis
      patients?
AB  - As low-field MR imaging is becoming a widely used imaging technique, we aimed at
      a prospective assessment of differences in imaging quality between low- and high
      field MR imaging in multiple sclerosis patients possibly interfering with
      diagnostic or therapeutic decision making. Twenty patients with clinically proven
      multiple sclerosis were examined with optimized imaging protocols in a 1.5- and a
      0.23-T MR scanner within 48 h. Images were assessed independently by two
      neuroradiologists. No statistically significant interrater discrepancies were
      observed. A significantly lower number of white matter lesions could be
      identified in low-field MR imaging both on T1- and on T2-weighted images (T2:
      high field 700, low field 481; T1: high field 253, low field 177). A total of 114
      enhancing lesions were discerned in the high-field MR imaging as opposed to 45
      enhancing lesions in low-field MR imaging. Blood-brain barrier disruption was
      identified in 11 of 20 patients in the high-field MR imaging, but only in 4 of 20
      patients in low-field MR imaging. Since a significantly lower lesion load is
      identified in low-field MR imaging than in high-field MR imaging, and blood-brain
      barrier disruption is frequently missed, caution must be exercised in
      interpreting a normal low-field MR imaging scan in a patient with clinical signs
      of multiple sclerosis and in interpreting a scan without enhancing lesions in a
      patient with known multiple sclerosis and clinical signs of exacerbation.

PMID- 11519564
TI  - MR spectroscopy detection of lactate and lipid signals in the brains of healthy
      elderly people.
AB  - Magnetic resonance spectroscopy was used to assess the presence of brain lactate
      and lipid signals, frequently associated with the presence of pathology, in
      healthy persons of 60-90 years old (n = 540). Lactate and lipid signals were
      observed in, respectively, 25 and 6% of women, and 18 and 2% of men. Upon
      adjustment for age, and for MRI-detected cerebral atrophy and white matter
      lesions, the gender differences in lactate and lipid remained the same (p = 0.05
      and p = 0.03, respectively). Brain lactate and lipid signals appear to be
      intrinsic to aging. However, the presence of these metabolites in very focal
      areas only, rather than in any distributed fashion within the brain (the latter
      generally the case with cerebral atrophy and white matter lesions), strongly
      suggests the existence of asymptomatic focal pathology not shown on MRI.

PMID- 11519565
TI  - Assessment of intraocular foreign bodies by helical-CT multiplanar imaging.
AB  - The aim of this study was to examine the effectiveness of helical CT in the
      assessment of intraocular foreign bodies, evaluating two protocols with different
      collimation. We performed helical-CT studies in 30 patients. Fifteen patients
      were examined with 1.5-mm collimation and the other 15 patients with 3.0-mm
      collimation. All other imaging parameters were identical in both protocols.
      Multiplanar images were reconstructed. The examinations were reviewed for
      presence, localization and size of intraocular foreign bodies. We compare our
      results with the surgical data. We estimate the required examination time. In the
      first group (collimation 1.5 mm) an intraorbital foreign body was detected in 8
      of 15 patients. In 3 of 8 patients an intraocular foreign body (all were
      metallic) was detected. In the second group (collimation 3.0 mm) an intraorbital
      foreign body was detected in 9 of 15 patients. In 8 of 9 patients an intraocular
      foreign body (all were metallic) was detected. Our results were confirmed by
      surgery in all cases. Examination time was 36 s in the first group and 18 s in
      the second group. Computed tomography should be considered the imaging modality
      of choice in the assessment of metallic intraocular foreign bodies and 3.0-mm
      collimation is optional, because of reduced examination time and radiation
      exposure.

PMID- 11519566
TI  - Malignant lymphoma of the cranial vault in an HIV-positive patient: imaging
      findings.
AB  - We describe the CT and MR imaging findings in an HIV-positive patient with
      malignant non-Hodgkin's lymphoma of the cranial vault, a rare site for lymphoma
      involvement. Autopsy revealed lymphomatous bone lesions, lymphoma in the epidural
      space, and a large necrotic lymphoma in the soft tissue of the skull.

PMID- 11519568
TI  - All-trans retinoic acid syndrome: chest CT assessment.

PMID- 11519567
TI  - Fractal analyses of osseous healing using tuned aperture computed tomography
      images.
AB  - The aim of this study was to evaluate osseous healing in mandibular defects using
      fractal analyses on conventional radiographs and tuned aperture computed
      tomography (TACT; OrthoTACT, Instrumentarium Imaging, Helsinki, Finland) images.
      Eighty test sites on the inferior margins of rabbit mandibles were subject to
      lesion induction and treated with one of the following: no treatment (controls);
      osteoblasts only; polymer matrix only; or osteoblast-polymer matrix (OPM)
      combination. Images were acquired using conventional radiography and TACT,
      including unprocessed TACT (TACT-U) and iteratively restored TACT (TACT-IR).
      Healing was followed up over time and images acquired at 3, 6, 9, and 12 weeks
      post-surgery. Fractal dimension (FD) was computed within regions of interest in
      the defects using the TACT workbench. Results were analyzed for effects produced
      by imaging modality, treatment modality, time after surgery and lesion location.
      Histomorphometric data were available to assess ground truth. Significant
      differences (p < 0.0001) were noted based on imaging modality with TACT-IR
      recording the highest mean fractal dimension (MFD), followed by TACT-U and
      conventional images, in that order. Sites treated with OPM recorded the highest
      MFDs among all treatment modalities (p < 0.0001). The highest MFD based on time
      was recorded at 3 weeks and differed significantly with 12 weeks (p < 0.035).
      Correlation of FD with results of histomorphometric data was high (r = 0.79; p <
      0.001). The FD computed on TACT-IR showed the highest correlation with
      histomorphometric data, thus establishing the fact TACT is a more efficient and
      accurate imaging modality for quantification of osseous changes within healing
      bony defects.

PMID- 11519569
TI  - Auditory detection of hollowness.
AB  - The airborne sounds produced by freely vibrating hollow and solid bars were
      synthesized according to the equations of bar motion from theoretical acoustics,
      and were presented to listeners over headphones. In a two-interval, forced-choice
      task, listeners were asked to distinguish between the hollow and solid bar sounds
      as bar length was varied at random from one presentation to the next. All other
      physical properties of the bar were held constant across trials. Listener
      decision strategies for detecting hollowness in iron, aluminum, and wood bars
      were determined from regression weights describing the relation between the
      listener's response and the frequency, intensity, and decay modulus of the
      individual partials comprising these sounds. The obtained weights were compared
      to those of a hypothetical listener that bases judgments on the acoustic
      relations intrinsic to hollowness, as determined from the equations for motion.
      Results indicate that listeners adopt roughly one of two decision strategies,
      either basing judgments on the appropriate acoustic relations, or basing
      judgments predominantly on frequency alone. The decision strategy of some
      listeners also changed from one type to the other with a change in bar material
      or upon replication of the same condition. The results are interpreted in terms
      of the vulnerability of the intrinsic acoustic relations to small perturbations
      in acoustic parameters, as would be associated with listener internal noise. They
      demonstrate that basic limits of human sensitivity can have a profound effect on
      the identification of rudimentary source attributes from sound, even in
      conditions where acoustic variation is largely dictated by physical variation in
      the source.

PMID- 11519570
TI  - Interaural correlation sensitivity.
AB  - Sensitivity to differences in interaural correlation was measured for 1.3-ERB
      wide bands of noise using a 2IFC task at six frequencies: 250, 500, 750, 1000,
      1250, and 1500 Hz. The sensitivity index, d', was measured for discriminations
      between a number of fixed pairs of correlation values. Cumulative d' functions
      were derived for each frequency and condition. The d' for discriminating any two
      values of correlation may be recovered from the cumulative d' function by the
      difference between cumulative d''s for these values. Two conditions were
      employed: the noisebands were either presented in isolation (narrow-band
      condition) or in the context of broad, contiguous flanking bands of correlated
      noise (fringed condition). The cumulative d' functions showed greater sensitivity
      to differences in correlation close to 1 than close to 0 at low frequencies, but
      this difference was less pronounced in the fringed condition. Also, a more linear
      relationship was observed when cumulative d' was plotted as a function of the
      equivalent signal-to-noise ratio (SNR) in dB for each correlation value, rather
      than directly against correlation. The equivalent SNR was the SNR at which the
      interaural correlation in an NoS(pi) stimulus would equal the interaural
      correlation of the noise used in the experiment. The maximum cumulative d'
      declined above 750 Hz. This decline was steeper for the fringed than for the
      narrow-band condition. For the narrow-band condition, the total cumulative d' was
      variable across listeners. All cumulative d' functions were closely fitted using
      a simple two-parameter function. The complete data sets, averaged across
      listeners, from the fringed and narrow-band conditions were fitted using
      functions to describe the changes in these parameters over frequency, in order to
      produce an interpolated family of curves that describe sensitivity at frequencies
      between those tested. These curves predict the spectra recovered by the binaural
      system when complex sounds, such as speech, are masked by noise.

PMID- 11519571
TI  - Second-order temporal modulation transfer functions.
AB  - Detection thresholds were measured for a sinusoidal modulation applied to the
      modulation depth of a sinusoidally amplitude-modulated (SAM) white noise carrier
      as a function of the frequency of the modulation applied to the modulation depth
      (referred to as f'm). The SAM noise acted therefore as a "carrier" stimulus of
      frequency fm, and sinusoidal modulation of the SAM-noise modulation depth
      generated two additional components in the modulation spectrum: fm-f'm and
      fm+f'm. The tracking variable was the modulation depth of the sinusoidal
      variation applied to the "carrier" modulation depth. The resulting "second-order"
      temporal modulation transfer functions (TMTFs) measured on four listeners for
      "carrier" modulation frequencies fm of 16, 64, and 256 Hz display a low-pass
      segment followed by a plateau. This indicates that sensitivity to fluctuations in
      the strength of amplitude modulation is best for fluctuation rates f'm below
      about 2-4 Hz when using broadband noise carriers. Measurements of masked
      modulation detection thresholds for the lower and upper modulation sideband
      suggest that this capacity is possibly related to the detection of a beat in the
      sound's temporal envelope. The results appear qualitatively consistent with the
      predictions of an envelope detector model consisting of a low-pass filtering
      stage followed by a decision stage. Unlike listeners' performance, a modulation
      filterbank model using Q values > or = 2 should predict that second-order
      modulation detection thresholds should decrease at high values of f'm due to the
      spectral resolution of the modulation sidebands (in the modulation domain). This
      suggests that, if such modulation filters do exist, their selectivity is poor. In
      the latter case, the Q value of modulation filters would have to be less than 2.
      This estimate of modulation filter selectivity is consistent with the results of
      a previous study using a modulation-masking paradigm [S. D. Ewert and T. Dau, J.
      Acoust. Soc. Am. 108, 1181-1196 (2000)].

PMID- 11519572
TI  - Exploring the temporal mechanism involved in the pitch of unresolved harmonics.
AB  - This paper continues a line of research initiated by Kaernbach and Demany [J.
      Acoust. Soc. Am. 104, 2298-2306 (1998)], who employed filtered click sequences to
      explore the temporal mechanism involved in the pitch of unresolved harmonics. In
      a first experiment, the just noticeable difference (jnd) for the fundamental
      frequency (F0) of high-pass filtered and low-pass masked click trains was
      measured, with F0 (100 to 250 Hz) and the cut frequency (0.5 to 6 kHz) being
      varied orthogonally. The data confirm the result of Houtsma and Smurzynski [J.
      Acoust. Soc. Am. 87, 304-310 (1990)] that a pitch mechanism working on the
      temporal structure of the signal is responsible for analyzing frequencies higher
      than ten times the fundamental. Using high-pass filtered click trains, however,
      the jnd for the temporal analysis is at 1.2% as compared to 2%-3% found in
      studies using band-pass filtered stimuli. Two further experiments provide
      evidence that the pitch of this stimulus can convey musical information. A fourth
      experiment replicates the finding of Kaernbach and Demany on first- and second
      order regularities with a cut frequency of 2 kHz and extends the paradigm to
      binaural aperiodic click sequences. The result suggests that listeners can detect
      first-order temporal regularities in monaural click streams as well as in
      binaurally fused click streams.

PMID- 11519573
TI  - Forward- and simultaneous-masked thresholds in bandlimited maskers in subjects
      with normal hearing and cochlear hearing loss.
AB  - Forward- and simultaneous-masked thresholds were measured at 0.5 and 2.0 kHz in
      bandpass maskers as a function of masker bandwidth and in a broadband masker with
      the goal of estimating psychophysical suppression. Suppression was operationally
      defined in two ways: (1) as a change in forward-masked threshold as a function of
      masker bandwidth, and (2) as a change in effective masker level with increased
      masker bandwidth, taking into account the nonlinear growth of forward masking.
      Subjects were younger adults with normal hearing and older adults with cochlear
      hearing loss. Thresholds decreased as a function of masker bandwidth in forward
      masking, which was attributed to effects of suppression; thresholds remained
      constant or increased slightly with increasing masker bandwidth in simultaneous
      masking. For subjects with normal hearing, slightly larger estimates of
      suppression were obtained at 2.0 kHz rather than at 0.5 kHz. For hearing-impaired
      subjects, suppression was reduced in regions of hearing loss. The magnitude of
      suppression was strongly correlated with the absolute threshold at the signal
      frequency, but did not vary with thresholds at frequencies remote from the
      signal. The results suggest that measuring forward-masked thresholds in
      bandlimited and broadband maskers may be an efficient psychophysical method for
      estimating suppression.

PMID- 11519574
TI  - Psychophysical suppression measured with bandlimited noise extended below and/or
      above the signal: effects of age and hearing loss.
AB  - The objectives of this study were to measure suppression with bandlimited noise
      extended below and above the signal, at lower and higher signal frequencies,
      between younger and older subjects, and between subjects with normal hearing and
      cochlear hearing loss. Psychophysical suppression was assessed by measuring
      forward-masked thresholds at 0.8 and 2.0 kHz in bandlimited maskers as a function
      of masker bandwidth. Bandpass-masker bandwidth was increased by introducing noise
      components below and above the signal frequency while keeping the noise centered
      on the signal frequency, and also by adding noise below the signal only, and
      above the signal only. Subjects were younger and older adults with normal hearing
      and older adults with cochlear hearing loss. For all subjects, suppression was
      larger when noise was added below the signal than when noise was added above the
      signal, consistent with some physiological evidence of stronger suppression below
      a fiber's characteristic frequency than above. For subjects with normal hearing,
      suppression was greater at higher than at lower frequencies. For older subjects
      with hearing loss, suppression was reduced to a greater extent above the signal
      than below and where thresholds were elevated. Suppression for older subjects
      with normal hearing was poorer than would be predicted from their absolute
      thresholds, suggesting that age may have contributed to reduced suppression or
      that suppression was sensitive to changes in cochlear function that did not
      result in significant threshold elevation.

PMID- 11519575
TI  - Temporal modulation transfer functions obtained using sinusoidal carriers with
      normally hearing and hearing-impaired listeners.
AB  - Temporal modulation transfer functions were obtained using sinusoidal carriers
      for four normally hearing subjects and three subjects with mild to moderate
      cochlear hearing loss. Carrier frequencies were 1000, 2000 and 5000 Hz, and
      modulation frequencies ranged from 10 to 640 Hz in one-octave steps. The normally
      hearing subjects were tested using levels of 30 and 80 dB SPL. For the higher
      level, modulation detection thresholds varied only slightly with modulation
      frequency for frequencies up to 80 Hz, but decreased for high modulation
      frequencies. The decrease can be attributed to the detection of spectral
      sidebands. For the lower level, thresholds varied little with modulation
      frequency for all three carrier frequencies. The absence of a decrease in the
      threshold for large modulation frequencies can be explained by the low sensation
      level of the spectral sidebands. The hearing-impaired subjects were tested at 80
      dB SPL, except for two cases where the absolute threshold at the carrier
      frequency was greater than 70 dB SPL; in these cases a level of 90 dB was used.
      The results were consistent with the idea that spectral sidebands were less
      detectable for the hearing-impaired than for the normally hearing subjects. For
      the two lower carrier frequencies, there were no large decreases in threshold
      with increasing modulation frequency, and where decreases did occur, this
      happened only between 320 and 640 Hz. For the 5000-Hz carrier, thresholds were
      roughly constant for modulation frequencies from 10 to 80 or 160 Hz, and then
      increased monotonically, becoming unmeasurable at 640 Hz. The results for this
      carrier may reflect "pure" effects of temporal resolution, without any influence
      from the detection of spectral sidebands. The results suggest that temporal
      resolution for deterministic stimuli is similar for normally hearing and hearing
      impaired listeners.

PMID- 11519576
TI  - Binaural processing model based on contralateral inhibition. I. Model structure.
AB  - This article presents a quantitative binaural signal detection model which
      extends the monaural model described by Dau et al. [J. Acoust. Soc. Am. 99, 3615
      3622 (1996)]. The model is divided into three stages. The first stage comprises
      peripheral preprocessing in the right and left monaural channels. The second
      stage is a binaural processor which produces a time-dependent internal
      representation of the binaurally presented stimuli. This stage is based on the
      Jeffress delay line extended with tapped attenuator lines. Through this
      extension, the internal representation codes both interaural time and intensity
      differences. In contrast to most present-day models, which are based on
      excitatory-excitatory interaction, the binaural interaction in the present model
      is based on contralateral inhibition of ipsilateral signals. The last stage, a
      central processor, extracts a decision variable that can be used to detect the
      presence of a signal in a detection task, but could also derive information about
      the position and the compactness of a sound source. In two accompanying articles,
      the model predictions are compared with data obtained with human observers in a
      great variety of experimental conditions.

PMID- 11519577
TI  - Binaural processing model based on contralateral inhibition. II. Dependence on
      spectral parameters.
AB  - This and two accompanying articles [Breebaart et al., J. Acoust. Soc. Am. 110,
      1074-1088 (2001); 110, 1105-1117 (2001)] describe a computational model for the
      signal processing in the binaural auditory system. The model consists of several
      stages of monaural and binaural preprocessing combined with an optimal detector.
      In the present article the model is tested and validated by comparing its
      predictions with experimental data for binaural discrimination and masking
      conditions as a function of the spectral parameters of both masker and signal.
      For this purpose, the model is used as an artificial observer in a three
      interval, forced-choice adaptive procedure. All model parameters were kept
      constant for all simulations described in this and the subsequent article. The
      effects of the following experimental parameters were investigated: center
      frequency of both masker and target, bandwidth of masker and target, the
      interaural phase relations of masker and target, and the level of the masker.
      Several phenomena that occur in binaural listening conditions can be accounted
      for. These include the wider effective binaural critical bandwidth observed in
      band-widening NoS(pi) conditions, the different masker-level dependence of
      binaural detection thresholds for narrow- and for wide-band maskers, the
      unification of IID and ITD sensitivity with binaural detection data, and the
      dependence of binaural thresholds on frequency.

PMID- 11519578
TI  - Binaural processing model based on contralateral inhibition. III. Dependence on
      temporal parameters.
AB  - This paper and two accompanying papers [Breebaart et al., J. Acoust. Soc. Am.
      110, 1074-1088 (2001); 110, 1089-1104 (2001)] describe a computational model for
      the signal processing of the binaural auditory system. The model consists of
      several stages of monaural and binaural preprocessing combined with an optimal
      detector. Simulations of binaural masking experiments were performed as a
      function of temporal stimulus parameters and compared to psychophysical data
      adapted from literature. For this purpose, the model was used as an artificial
      observer in a three-interval, forced-choice procedure. All model parameters were
      kept constant for all simulations. Model predictions were obtained as a function
      of the interaural correlation of a masking noise and as a function of both masker
      and signal duration. Furthermore, maskers with a time-varying interaural
      correlation were used. Predictions were also obtained for stimuli with time
      varying interaural time or intensity differences. Finally, binaural forward
      masking conditions were simulated. The results show that the combination of a
      temporal integrator followed by an optimal detector in the time domain can
      account for all conditions that were tested, except for those using periodically
      varying interaural time differences (ITDs) and those measuring interaural
      correlation just-noticeable differences (jnd's) as a function of bandwidth.

PMID- 11519579
TI  - Spatial unmasking of nearby speech sources in a simulated anechoic environment.
AB  - Spatial unmasking of speech has traditionally been studied with target and masker
      at the same, relatively large distance. The present study investigated spatial
      unmasking for configurations in which the simulated sources varied in azimuth and
      could be either near or far from the head. Target sentences and speech-shaped
      noise maskers were simulated over headphones using head-related transfer
      functions derived from a spherical-head model. Speech reception thresholds were
      measured adaptively, varying target level while keeping the masker level constant
      at the "better" ear. Results demonstrate that small positional changes can result
      in very large changes in speech intelligibility when sources are near the
      listener as a result of large changes in the overall level of the stimuli
      reaching the ears. In addition, the difference in the target-to-masker ratios at
      the two ears can be substantially larger for nearby sources than for relatively
      distant sources. Predictions from an existing model of binaural speech
      intelligibility are in good agreement with results from all conditions comparable
      to those that have been tested previously. However, small but important
      deviations between the measured and predicted results are observed for other
      spatial configurations, suggesting that current theories do not accurately
      account for speech intelligibility for some of the novel spatial configurations
      tested.

PMID- 11519580
TI  - Consonant identification under maskers with sinusoidal modulation: masking
      release or modulation interference?
AB  - The present study investigated the effect of envelope modulations in a background
      masker on consonant recognition by normal hearing listeners. It is well known
      that listeners understand speech better under a temporally modulated masker than
      under a steady masker at the same level, due to masking release. The possibility
      of an opposite phenomenon, modulation interference, whereby speech recognition
      could be degraded by a modulated masker due to interference with auditory
      processing of the speech envelope, was hypothesized and tested under various
      speech and masker conditions. It was of interest whether modulation interference
      for speech perception, if it were observed, could be predicted by modulation
      masking, as found in psychoacoustic studies using nonspeech stimuli. Results
      revealed that masking release measurably occurred under a variety of conditions,
      especially when the speech signal maintained a high degree of redundancy across
      several frequency bands. Modulation interference was also clearly observed under
      several circumstances when the speech signal did not contain a high redundancy.
      However, the effect of modulation interference did not follow the expected
      pattern from psychoacoustic modulation masking results. In conclusion, (1) both
      factors, modulation interference and masking release, should be accounted for
      whenever a background masker contains temporal fluctuations, and (2) caution
      needs to be taken when psychoacoustic theory on modulation masking is applied to
      speech recognition.

PMID- 11519581
TI  - On the effectiveness of whole spectral shape for vowel perception.
AB  - The formant hypothesis of vowel perception, where the lowest two or three formant
      frequencies are essential cues for vowel quality perception, is widely accepted.
      There has, however, been some controversy suggesting that formant frequencies are
      not sufficient and that the whole spectral shape is necessary for perception.
      Three psychophysical experiments were performed to study this question. In the
      first experiment, the first or second formant peak of stimuli was suppressed as
      much as possible while still maintaining the original spectral shape. The
      responses to these stimuli were not radically different from the ones for the
      unsuppressed control. In the second experiment, F2-suppressed stimuli, whose
      amplitude ratios of high- to low-frequency components were systemically changed,
      were used. The results indicate that the ratio changes can affect perceived vowel
      quality, especially its place of articulation. In the third experiment, the full
      formant stimuli, whose amplitude ratios were changed from the original and whose
      F2's were kept constant, were used. The results suggest that the amplitude ratio
      is equal to or more effective than F2 as a cue for place of articulation. We
      conclude that formant frequencies are not exclusive cues and that the whole
      spectral shape can be crucial for vowel perception.

PMID- 11519582
TI  - Speech recognition in noise as a function of the number of spectral channels:
      comparison of acoustic hearing and cochlear implants.
AB  - Speech recognition was measured as a function of spectral resolution (number of
      spectral channels) and speech-to-noise ratio in normal-hearing (NH) and cochlear
      implant (CI) listeners. Vowel, consonant, word, and sentence recognition were
      measured in five normal-hearing listeners, ten listeners with the Nucleus-22
      cochlear implant, and nine listeners with the Advanced Bionics Clarion cochlear
      implant. Recognition was measured as a function of the number of spectral
      channels (noise bands or electrodes) at signal-to-noise ratios of + 15, + 10, +5,
      0 dB, and in quiet. Performance with three different speech processing strategies
      (SPEAK, CIS, and SAS) was similar across all conditions, and improved as the
      number of electrodes increased (up to seven or eight) for all conditions. For all
      noise levels, vowel and consonant recognition with the SPEAK speech processor did
      not improve with more than seven electrodes, while for normal-hearing listeners,
      performance continued to increase up to at least 20 channels. Speech recognition
      on more difficult speech materials (word and sentence recognition) showed a
      marginally significant increase in Nucleus-22 listeners from seven to ten
      electrodes. The average implant score on all processing strategies was poorer
      than scores of NH listeners with similar processing. However, the best CI scores
      were similar to the normal-hearing scores for that condition (up to seven
      channels). CI listeners with the highest performance level increased in
      performance as the number of electrodes increased up to seven, while CI listeners
      with low levels of speech recognition did not increase in performance as the
      number of electrodes was increased beyond four. These results quantify the effect
      of number of spectral channels on speech recognition in noise and demonstrate
      that most CI subjects are not able to fully utilize the spectral information
      provided by the number of electrodes used in their implant.

PMID- 11519583
TI  - Effects of low-pass filtering on the intelligibility of speech in quiet for
      people with and without dead regions at high frequencies.
AB  - A dead region is a region of the cochlea where there are no functioning inner
      hair cells (IHCs) and/or neurons; it can be characterized in terms of the
      characteristic frequencies of the IHCs bordering that region. We examined the
      effect of high-frequency amplification on speech perception for subjects with
      high-frequency hearing loss with and without dead regions. The limits of any dead
      regions were defined by measuring psychophysical tuning curves and were confirmed
      using the TEN test described in Moore et al. [Br. J. Audiol. 34, 205-224 (2000)].
      The speech stimuli were vowel-consonant-vowel (VCV) nonsense syllables, using one
      of three vowels (/i/, /a/, and /u/) and 21 different consonants. In a baseline
      condition, subjects were tested using broadband stimuli with a nominal input
      level of 65 dB SPL. Prior to presentation via Sennheiser HD580 earphones, the
      stimuli were subjected to the frequency-gain characteristic prescribed by the
      "Cambridge" formula, which is intended to give speech at 65 dB SPL the same
      overall loudness as for a normal listener, and to make the average loudness of
      the speech the same for each critical band over the frequency range important for
      speech intelligibility (in a listener without a dead region). The stimuli for all
      other conditions were initially subjected to this same frequency-gain
      characteristic. Then, the speech was low-pass filtered with various cutoff
      frequencies. For subjects without dead regions, performance generally improved
      progressively with increasing cutoff frequency. This indicates that they
      benefited from high-frequency information. For subjects with dead regions, two
      patterns of performance were observed. For most subjects, performance improved
      with increasing cutoff frequency until the cutoff frequency was somewhat above
      the estimated edge frequency of the dead region, but hardly changed with further
      increases. For a few subjects, performance initially improved with increasing
      cutoff frequency and then worsened with further increases, although the worsening
      was significant only for one subject. The results have important implications for
      the fitting of hearing aids.

PMID- 11519584
TI  - A computational sensorimotor model of bat echolocation.
AB  - A computational sensorimotor model of target capture behavior by the echolocating
      bat, Eptesicus fuscus, was developed to understand the detection, localization,
      tracking, and interception of insect prey in a biological sonar system. This
      model incorporated acoustics, target localization processes, flight aerodynamics,
      and target capture planning to produce model trajectories replicating those
      observed in behavioral insect capture trials. Estimates of target range were
      based on echo delay, azimuth on the relative intensity of the echo at the two
      ears, and elevation on the spectral pattern of the sonar return in a
      match/mismatch process. Flapping flight aerodynamics was used to produce
      realistic model trajectories. Localization in all three spatial dimensions proved
      necessary to control target tracking and interception for an adequate model of
      insect capture behavior by echolocating bats. Target capture using maneuvering
      flight was generally successful when the model's path was controlled by a
      planning process that made use of an anticipatory internal simulation, while
      simple homing was successful only for targets directly ahead of the model bat.

PMID- 11519585
TI  - Comment on "Free vibration analysis of laminated piezoceramic hollow spheres".

PMID- 11519589
TI  - A method for studying variability in fricatives using dynamic measures of
      spectral mean.

PMID- 11519618
TI  - General scales of community reaction to noise (dissatisfaction and perceived
      affectedness) are more reliable than scales of annoyance.
AB  - General measures of reaction to noise, which assess the respondent's perceived
      affectedness or dissatisfaction, appear to be more valid and internally
      consistent than more narrow measures, such as specific assessment of noise
      annoyance. However, the test-retest reliability of general and specific measures
      has yet to be compared. As a part of the large-scale Sydney Airport Health Study,
      97 respondents participated in the same interview twice, several weeks apart.
      Test-retest reliabilities were found to be significant (p < 0.001) for two
      general questions and three specific "annoyance" questions. The general measures
      were significantly more valid for four of the six correlations (with activity
      disturbance), and more stable than the annoyance scales for five of the six
      possible test-retest comparisons. Amongst 1,015 respondents at Time 1, the
      questions regarding general reaction were more internally consistent than the
      questions regarding annoyance. Taken together, these data indicate that general
      measures of reaction to noise have superior psychometric properties (validity,
      internal consistency, and stability) compared with measures of specific reactions
      such as annoyance.

PMID- 11519622
TI  - The behavior of evoked otoacoustic emissions during and after postural changes.
AB  - Click-evoked and stimulus frequency otoacoustic emissions (CEOAEs and SFOAEs,
      respectively) were studied in humans during and after postural changes. The
      subjects were tilted from upright to a recumbent position (head down 30 deg) and
      upright again. Due to the downward posture change, CEOAEs showed a phase increase
      (80 deg at 1 kHz) and a level decrease (0.5 at 1 kHz), especially for frequency
      components below 2 kHz. For SFOAEs, the typical ripple pattern showed a positive
      shift along the frequency axis, which can be interpreted as a phase shift of the
      inner-ear component of the microphone signal (90 deg at 1 kHz). This also
      occurred mainly for frequencies below 2 kHz. The altered posture is thought to
      cause an increase of the intracranial pressure, and consequently of the
      intracochlear fluid pressure, which results in an increased stiffness of the
      stapes system. The observed emission changes are in agreement with predictions
      from a model in which the stiffness of the cochlear windows was altered. For
      CEOAEs, the time to regain stability after a downward turn was of the order of 30
      s, while this took about 20 s after an upward turn. For SFOAEs, this asymmetry
      was not found to be present (about 11 s, both for up- and downward turns).

PMID- 11519623
TI  - Basilar-membrane response to multicomponent stimuli in chinchilla.
AB  - The response of chinchilla basilar membrane in the basal region of the cochlea to
      multicomponent (1, 3, 5, 6, or 7) stimuli was studied using a laser
      interferometer. Three-component stimuli were amplitude-modulated signals with
      modulation depths that varied from 25% to 200% and the modulation frequency
      varied from 100 to 2000 Hz while the carrier frequency was set to the
      characteristic frequency of the region under study (approximately 6.3 to 9 kHz).
      Results indicate that, for certain modulation frequencies and depths, there is
      enhancement of the response. Responses to five equal-amplitude sine wave stimuli
      indicated the occurrence of nonlinear phenomena such as spectral edge
      enhancement, present when the frequency spacing was less than 200 Hz, and mutual
      suppression. For five-component stimuli, the first, third, or fifth component was
      placed at the characteristic frequency and the component frequency separation was
      varied over a 2-kHz range. Responses to seven component stimuli were similar to
      those of five-component stimuli. Six-component stimuli were generated by leaving
      out the center component of the seven-component stimuli. In the latter case, the
      center component was restored in the basilar-membrane response as a result of
      distortion-product generation in the nonlinear cochlea.

PMID- 11519624
TI  - Frequency specificity of the human auditory brainstem and middle latency
      responses using notched noise masking.
AB  - This study investigated the frequency specificity of the auditory brainstem and
      middle latency responses to 80 and 90 dB ppe SPL 500-Hz and 90 dB ppe SPL 2000-Hz
      tonebursts. The stimuli were brief (2-1-2 cycle) linear-gated tonebursts.
      ABR/MLRs were recorded using two electrode montages: (1) Cz-nape of neck and (2)
      Cz-ipsilateral earlobe. Cochlear contributions to ABR wave V-Na and MLR waves Na
      Pa and Pa-Nb were assessed by plotting notched noise tuning curves which showed
      amplitudes and latencies as a function of center frequency of the noise masker
      [Abdala and Folsom, J. Acoust. Soc. Am. 97, 2394 (1995); ibid. 98, 921 (1995)].
      Maxima in the response amplitude profiles for the ABR and MLR to 80 dB ppe SPL
      tonebursts occurred within one-half octave of the nominal stimulus frequency,
      with minimal contributions to the responses from frequencies greater than one
      octave away. At 90 dB ppe SPL, contributions came from a slightly broader
      frequency region for both stimulus frequencies. Thus, the ABR/MLR to 80 dB ppe
      SPL tonebursts shows good frequency specificity which decreases at 90 dB ppe SPL.
      No significant differences exist in frequency specificity of: (1) ABR wave V-Na
      versus MLR waves Na-Pa and Pa-Nb at either stimulus frequency or intensity; and
      (2) ABR/MLRs recorded using the two electrode montages.

PMID- 11519625
TI  - The impact of familial alcoholism on alcohol reactivity in female social
      drinkers.
AB  - Some individuals may have an inherent reactivity to alcohol that facilitates
      early development of characteristics associated with alcoholism. Although
      response to alcohol cues has been used to assess this reactivity, few studies
      have included women or investigated familial alcoholism as a variable. In this
      study, 23 female college students were divided into groups according to family
      history of alcoholism (positive or negative). Alcohol reactivity was measured by
      salivation, skin temperature, heart rate, mood state, and craving for alcohol
      following presentation of alcohol-related and neutral cues. Results indicate no
      correlation between salivary reactivity and alcohol craving, which suggests that
      these variables tap into different domains of cue reactivity. Findings
      demonstrate that alcohol cue reactivity can be assessed in female social drinkers
      and that familial alcoholism may influence salivary reactivity to alcohol-related
      cues.

PMID- 11519626
TI  - Negligible tolerance produced by chronic intravenous alprazolam administration: a
      low serum drug concentration effect.
AB  - In 3-hr sessions, the authors investigated the onset, peak, and disappearance of
      the effects of alprazolam on performance under a differential reinforcement of
      low rate 45-s schedule in rats. Alprazolam was administered chronically as a
      daily bolus dose (2 mg/kg) via the intravenous route. Alprazolam decreased the
      reinforcement rate and increased the shorter response (nonreinforced) rate in a
      dose- and time-related fashion. Tolerance did not develop to the decreases in
      reinforcement rate; tolerance to increases in shorter response rate was
      negligible, occurring only at the low-concentration range. Clinically, an optimal
      dose regimen should be designed to avoid the tolerance development that occurs in
      the low serum benzodiazepine concentration range.

PMID- 11519627
TI  - Perceived vulnerability to alcohol-related harm in young adults: independent
      effects of risky alcohol use and drinking motives.
AB  - Perceived vulnerability to negative outcomes can motivate heavy drinkers to adopt
      health-protective behavior, but little is known about determinants of perceived
      vulnerability to alcohol-related harm. University students (N = 286) were
      assessed to determine epidemiological risk status on a standardized problem
      drinking measure, typical reasons for drinking and cutting down, and perceived
      risk of experiencing alcohol-related harm. Results showed a positive relationship
      between problem drinking status and perceived risk of experiencing harm. However,
      at-risk drinkers believed that they were less likely to personally experience
      harm than comparable peers (p < .001), whereas not-at-risk drinkers showed no
      self-other differences in perceived vulnerability. Drinking motives significantly
      improved the prediction of perceived vulnerability when epidemiological risk
      status was controlled. Perceived vulnerability to alcohol-related harm is
      affected by problem drinking status and (independently) by the psychological
      functions that drinking serves.

PMID- 11519629
TI  - Challenges in the transfer of contingency management techniques: comment on
      Silverman et al. (2001).
AB  - This article critiques K. Silverman, D. Svikis, E. Robles, M. L. Stitzer, and G.
      E. Bigelow's (2001) study of a contingency management intervention for
      reinforcing development of job-related skills in substance abusing women. The
      strengths of Silverman et al.'s study include studying a patient population of
      major public health concern, expanding contingency management techniques to a
      vocational training setting, reinforcing gradual approximations, implementing the
      intervention for a long duration, and carefully designing and executing the
      experimental procedures. However, many of these strengths may also be interpreted
      as weaknesses if the ultimate goal is to apply contingency management techniques
      in self-sustaining, community-based settings. The need to evaluate long-term cost
      effectiveness of these procedures is described, and the difficulties in
      transferring contingency management techniques to real-world settings is
      discussed.

PMID- 11519628
TI  - A reinforcement-based therapeutic workplace for the treatment of drug abuse: six
      month abstinence outcomes.
AB  - This study evaluated a novel drug abuse treatment, the Therapeutic Workplace. In
      this treatment, patients are paid to perform jobs or to participate in job
      training. Salary is linked to abstinence by requiring patients to provide drug
      free urine samples to gain access to the workplace. Pregnant and postpartum drug
      abuse patients (N = 40) were randomly assigned to a Therapeutic Workplace or
      usual care control group. Therapeutic Workplace participants were invited to work
      3 hr every weekday for 6 months and could earn up to $4,030 in vouchers for
      abstinence, workplace attendance, and performance. On average, 45% of
      participants attended the workplace per day. Relative to controls, the
      Therapeutic Workplace nearly doubled patients' abstinence from opiates and
      cocaine (33% vs. 59% of thrice-weekly urine samples drug negative, respectively,
      p < .05). The Therapeutic Workplace can effectively treat heroin and cocaine
      abuse in pregnant and postpartum women.

PMID- 11519630
TI  - A promising intervention for a daunting problem: comment on Silverman et al.
      (2001).
AB  - Six features of the report are commented on. First, the Therapeutic Workplace
      intervention described in the report represents a creative and promising new
      approach to drug abuse treatment. Second, to the author's knowledge, it
      represents the first intervention that has been shown in a randomized clinical
      trial to significantly reduce cocaine abuse among pregnant women. Third, the
      report and study are commendable for their scientific rigor. Fourth, the
      treatment approach is science-based, integrating concepts and principles from
      several behavioral science literatures. Fifth, the intervention offers a
      potentially practical way of extending incentive-based drug abuse treatments to
      community clinics. Sixth and last, the report has the potential to provoke
      serious thought and consideration of what more might be done to combat the
      daunting and related problems of chronic unemployment and drug abuse in our
      poorer communities.

PMID- 11519631
TI  - Moving toward a "third generation" of contingency management studies in the abuse
      treatment field: comment on Silverman et al. (2001).
AB  - The power of positively reinforced contingency management procedures has been
      definitively proven in the drug abuse field-even among the most severely affected
      clients. This study by K. Silverman, D. Svikis, E. Robles, M. L. Stitzer, and G.
      E. Bigelow (2001) and other studies like it have clearly moved the contingency
      management work out of controlled, contrived settings and into the real world.
      Suggestions are offered for moving the next generation of studies toward less
      complicated populations and using more robust reinforcements within the
      constraints of contemporary financial and administrative boundaries.

PMID- 11519633
TI  - Integrating contingency management with relapse prevention skills: comment on
      Silverman et al. (2001).
AB  - The study by K. Silverman, D. Svikis, E. Robles, M. L. Stitzer, and G. E. Bigelow
      (2001) demonstrates the effectiveness of a voucher-based reinforcement
      intervention in the treatment of pregnant women in treatment for substance abuse.
      The effects of prolonged initial abstinence as a form of "sobriety sampling" may
      serve to enhance long-term recovery by providing patients with rewards for
      maintaining abstinence. Several limitations to the study are addressed, including
      selection of the treatment sample and the absence of any follow-up data on drug
      use or relapse following completion of the 24-week treatment program.
      Recommendations are made to enhance maintenance of abstinence by providing coping
      skill training for relapse prevention as an addition to the contingency
      management approach.

PMID- 11519632
TI  - A review of the effects of perceived drug use opportunity of self-reported urge.
AB  - Although persons addicted to drugs reliably report experiencing cravings or urges
      during drug cue exposure, less is known about factors that may moderate this
      effect. This article reviews cue exposure studies with people who smoke, are
      dependent on alcohol, or are addicted to cocaine or opiates. Perceived drug use
      opportunity is found to affect urge ratings. Specifically, people who are
      addicted to substances and who perceive an opportunity to consume their drug of
      choice report higher urges than do those who do not anticipate being able to use
      the drug. This factor was proposed to explain why those in treatment for
      substance dependence report urges that are about half the strength of those in
      nontreatment settings. The impact of perceived drug use opportunity on urge is
      considered from a variety of perspectives, including conditioning theories, a
      cognitive appraisal framework, and motivated reasoning theory. Conceptual and
      methodological implications of perceived drug use opportunity are addressed.

PMID- 11519634
TI  - Human methadone self-administration: effects of diazepam pretreatment.
AB  - The effect of diazepam on methadone self-administration was examined. Five
      methadone-maintained patients with a history of benzodiazepine abuse were
      recruited. Patients were stabilized on 80 mg of methadone per day. After
      stabilization patients participated in methadone self-administration sessions.
      During each session, 128 presses (fixed ratio 128) of 1 button delivered 10 ml of
      0.054 mg/ml methadone solution. The same number of button presses on a 2nd button
      delivered 10 ml of vehicle. Forty-five min prior to the self-administration
      session, 0 (placebo), 5, 10, or 20 mg per 70 kg body weight diazepam was
      administered. Ratings of drug liking, goodness, strength, and high were collected
      5, 30, 60, 90, and 150 min after the end of the self-administration session.
      Diazepam pretreatment significantly decreased the amount of methadone consumed.
      The 10- and 20-mg diazepam doses significantly increased reports of good, like,
      strong, and high.

PMID- 11519635
TI  - The effects of housing costs on polydrug abuse patterns: a comparison of heroin,
      cocaine, and alcohol abusers.
AB  - This study evaluated how price of housing affects hypothetical purchasing
      decisions. Participants (26 heroin, 28 cocaine, and 15 alcohol abusers, and 25
      controls) were exposed to 4 conditions in which they "purchased" drugs, food,
      housing, and entertainment. Whereas income remained constant, housing prices
      varied across conditions. Except for 23% of heroin abusers, participants
      purchased housing regardless of cost, so that income increased as housing cost
      decreased. Demand for food was income inelastic, whereas demand for entertainment
      was income elastic. Each group showed income elastic demand for their drug of
      choice. Hypothetical choices were reliable; drug choices were correlated with
      urinalysis results, and willingness to forgo housing in the simulation was
      correlated with time spent homeless in real life. This study shows that changes
      in housing prices may affect choices for drug and nondrug reinforcers.

PMID- 11519636
TI  - Behavioral pharmacological similarities between methylphenidate and cocaine in
      cocaine abusers.
AB  - Six human participants with recent histories of cocaine use were trained to
      discriminate 200 mg oral cocaine hydrochloride. A range of doses of oral cocaine
      (50-300 mg), methylphenidate (15-90 mg), triazolam (0.125-0.75 mg), and placebo
      were then tested to determine whether they shared discriminative-stimulus and
      participant-rated effects with 200 mg cocaine. Cocaine and methylphenidate dose
      dependently increased cocaine-appropriate responding, produced prototypical
      stimulant-like participant-rated drug effects (e.g., increased participant
      ratings of Drug Liking), and increased heart rate and blood pressure. Triazolam
      produced low levels of cocaine-appropriate responding and impaired performance.
      Thus, consistent with previous studies, humans can reliably discriminate oral
      cocaine. Consistent with in vivo behavioral neuropharmacological data, the
      discriminative-stimulus, participant-rated, and physiological effects of oral
      cocaine and methylphenidate were similar.

PMID- 11519637
TI  - Risk taking by adolescents with maladaptive behavior histories.
AB  - "High-risk" adolescents with maladaptive behavior histories and control
      adolescents (15-17 years of age) participated in a laboratory experiment that
      measured aspects of risk-taking behavior. High-risk adolescents had behavioral
      profiles entailing combinations of past substance use disorder, early onset
      substance use, conduct disorder, criminal history, and dropping out of school. A
      risk-taking task presented participants with "risky" and nonrisky response
      options. The risky response option offered a low probability of a large monetary
      reward or a high probability of a smaller monetary loss and resulted in a net
      loss of monetary earnings. The nonrisky option protected current earnings. High
      risk adolescents chose the risky option more often, had lower overall earnings,
      and were more likely to persist in making (losing) risky responses following a
      single gain on the risky option. The data replicate previous findings with high
      risk adults.

PMID- 11519638
TI  - Effects of chronic nicotine and methylphenidate in adults with attention
      deficit/hyperactivity disorder.
AB  - Acute nicotine treatment has been found to reduce symptoms of attention
      deficit/hyperactivity disorder in adults (E. D. Levin, C. K. Conners, et al.,
      1996). In this study, chronic nicotine effects were compared with placebo and
      methylphenidate. Acute and chronic nicotine treatment significantly attenuated
      the rise in hit reaction time standard error over session blocks on the Conners
      Continuous Performance Test (C. K. Conners et al., 1996). Acute nicotine
      significantly reduced severity of clinical symptoms on the Clinical Global
      Impressions scale (National Institute of Mental Health, 1985). Nicotine caused a
      significant decrease in self-report of depressive mood as measured by the Profile
      of Mood States test (D. M. McNair, M. Lorr, & L. F. Droppleman, 1981). This small
      study (40 participants) provided evidence that nicotine treatment can reduce
      severity of attentional deficit symptoms and produce improvement on an objective
      computerized attention task.

PMID- 11519639
TI  - Subjective responses to nicotine in smokers may be associated with responses to
      caffeine and to alcohol.
AB  - Sensitivity in responses to one drug may relate to sensitivity to other drugs,
      suggesting broad individual differences in characteristic responsivity across
      drugs. Data from two separate studies of smokers were reanalyzed to examine
      associations between acute subjective and cardiovascular effects of nicotine vs.
      caffeine and between nicotine vs. alcohol. Typical intakes of cigarettes,
      alcohol, and caffeine were included as covariates when they were correlated with
      the responses of interest. Significant associations between nicotine and caffeine
      were seen for most of the subjective measures and for blood pressure responses.
      Fewer significant associations were observed between nicotine and alcohol.
      Responses associated between nicotine and both of the other drugs tended to
      reflect psychomotor stimulation. These results suggest that smokers who are more
      responsive to some of nicotine's subjective and blood pressure effects are also
      more sensitive to the same effects of caffeine and, to a lesser extent, of
      alcohol.

PMID- 11519640
TI  - Exploring the role of individual differences in the prediction of workplace
      aggression.
AB  - This study investigates the relationship between individual differences and the
      incidence of workplace aggression in a sample of employees from a transportation
      company and a public school system. Hierarchical multiple regression analysis
      indicated that measures of trait anger, attribution style, negative affectivity,
      attitudes toward revenge, self-control, and previous exposure to aggressive
      cultures accounted for 62% of the variance in the participants' self-reported
      incidence of workplace aggression. Further research on workplace aggression is
      advocated, focusing on the role of individual differences and their interactions
      with organizational and group-level variables.

PMID- 11519641
TI  - A longitudinal study of top-level executive performance.
AB  - Competency ratings were obtained from a hybrid selection system on 98 top-level
      executives in a predictive validity design. Hierarchical linear modeling results
      indicated that "resource problem-solving-oriented" competency ratings predicted
      initial performance. "People-oriented" competency ratings predicted subsequent
      performance trends. Utility estimates suggested that the system generated an
      additional $3 million in annual profit per candidate selected. Groups of
      executives with similar performance trends were identified who had encountered
      qualitatively different situational circumstances. Findings imply that a model of
      executive performance must contain main effects for person (competencies) and
      situation (economic-industrial) characteristics on both subsequent performance
      and performance trends. Future research needs to examine which situational
      circumstances moderate relationships between executive competencies and initial
      performance or subsequent performance trends.

PMID- 11519642
TI  - What I think you think of me: women's reactions to being viewed as beneficiaries
      of preferential selection.
AB  - Undergraduate women (N = 150) participated in 2 experimental studies designed to
      examine the effects of knowing that another believed they were beneficiaries of
      preferential selection. Results indicated that participants' awareness that the
      other viewed them as having been selected on the basis of gender rather than
      merit (a) prompted inferences that the other held negative expectations of their
      competence (Studies 1 and 2); (b) produced timid, performance-limiting task
      decisions as well as negative self-regard when they were uncertain about their
      task ability level (Studies 1 and 2): and (c) produced ambitious, performance
      maximizing task decisions when they knew themselves to be high in task ability
      and also were motivated to make a good impression (Study 2). In addition, in both
      studies negative affect resulted from the participants' knowledge that the other
      viewed them as having been preferentially selected.

PMID- 11519643
TI  - How negotiators get to yes: predicting the constellation of strategies used
      across cultures to negotiate conflict.
AB  - Individualism, hierarchy, polychronicity, and explicit-contracting values explain
      why managers from Germany, Japan, and the United States use a different mix of
      strategies to negotiate workplace conflict. Hypotheses extend prior research in
      showing that conflict behavior is multiply determined and that each culture uses
      a variety of interests, regulations, and power-based conflict management
      strategies. Results of actual (rather than survey-based) conflict resolution
      behavior suggest several fruitful avenues for future research, including
      examining the inferred meaning of negotiation arguments, analyzing interaction
      effects of cultural value dimensions, studying the effectiveness of different
      strategies across cultures, and examining whether strategic adjustments are made
      during intercultural conflict management.

PMID- 11519644
TI  - A trickle-down model of organizational justice: relating employees' and
      customers' perceptions of and reactions to fairness.
AB  - This study developed and tested a trickle-down model of organizational justice
      that hypothesized that employees' perceptions of fairness should affect their
      attitudes toward the organization, subsequently influencing their behaviors
      toward customers. In turn, customers should interpret these behaviors as signals
      of fair treatment, causing them to react positively to both the employee and the
      organization. The model was tested on a sample of 187 instructors and their
      students. The results revealed that instructors who perceived high distributive
      and procedural justice reported higher organizational commitment. In turn, their
      students reported higher levels of instructor effort, prosocial behaviors, and
      fairness, as well as more positive reactions to the instructor. Overall, the
      results imply that fair treatment of employees has important organizational
      consequences because of customers' attitudes and future intentions toward key
      service employees.

PMID- 11519645
TI  - The changing signs in the relationships among self-efficacy, personal goals, and
      performance.
AB  - The common interpretation of the positive correlation among self-efficacy,
      personal goals, and performance is questioned. Using self-efficacy theory (A.
      Bandura, 1977), it was predicted that cross-sectional correlational results were
      a function of past performance's influence on self-efficacy, and using control
      theory (W. T. Powers, 1973), it was predicted that self-efficacy could negatively
      influence subsequent performance. These predictions were supported with 56
      undergraduate participants, using a within-person procedure. Personal goals were
      also positively influenced by self-efficacy and performance but negatively
      related to subsequent performance. A 2nd study involving 185 undergraduates found
      that manipulated goal level positively predicted performance and self-efficacy
      positively predicted performance in the difficult-goal condition. The discussion
      focuses on conditions likely to affect the sign of the relationship among self
      efficacy, goals, and performance.

PMID- 11519646
TI  - Self-esteem and outcome fairness: differential importance of procedural and
      outcome considerations.
AB  - Results of a survey of 222 detainees in Dutch jails and police stations showed
      that outcome-fairness judgments of individuals with high self-esteem were more
      strongly related to outcome considerations than to procedural considerations,
      whereas outcome-fairness judgments of individuals with low self-esteem were more
      strongly related to procedural considerations than to outcome considerations.  It
      was proposed that these differences were due to the fact that (a) procedures more
      strongly express a social evaluation than outcomes and (b) individuals with low
      self-esteem are more concerned with social evaluations than individuals with high
      self-esteem.  The implications of the results for other individual-differences
      factors and other populations than detainees are discussed.

PMID- 11519647
TI  - The role of goal orientation following performance feedback.
AB  - This study examined the relationship of goal orientation and performance over a
      series of 2 challenging performance events. After providing performance feedback
      on the 1st event, the authors found that the relationship between a learning goal
      orientation and performance remained positive for the 2nd event, the relationship
      between a proving goal orientation and performance diminished from a positive to
      a nonsignificant level, and the relationship between an avoiding goal orientation
      and performance remained negative. Data analysis also indicated that the
      relationships between the 3 goal orientation dimensions and the performance event
      were differentially mediated by goal setting, self-efficacy, and effort.

PMID- 11519648
TI  - The effects of complexity on jurors' verdicts and construction of evidence.
AB  - One hundred twenty mock jurors heard 1 of several versions of a civil trial. The
      tort trial was either high or low in information load and contained evidence that
      either clearly favored the plaintiffs or was ambiguous. Expert witnesses
      testified in either technical or less technical language. Verdicts favored the
      plaintiffs when the evidence was clear and was presented in technical language
      because technical language enhanced witnesses' credibility when the evidence was
      clear. Although high information loads and technical language hindered evidence
      processing, jurors endeavored to comprehend, as indicated by the recall of more
      facts and alternative constructions of the evidence when that evidence was
      ambiguous. However. those constructions were of poorer quality, incorporating
      evidence of lesser probative value.

PMID- 11519649
TI  - How do people with different attachment styles balance work and family? A
      personality perspective on work-family linkage.
AB  - This study explored whether different models of work-family relationship were
      possible for individuals with different attachment styles. A mail survey was
      conducted using employees (N = 481) at a midwestern university in the United
      States. Results suggested that (a) individuals with a preoccupied attachment
      pattern were more likely to experience negative spillover from the family/home to
      the work domain than those with a secure or dismissing style, (b) securely
      attached individuals experienced positive spillover in both work and family
      domains more than those in the other groups, and (c) preoccupied individuals were
      much less likely to use a segmentation strategy than the other 3 attachment
      groups. However, when the conventional job satisfaction life satisfaction
      relationship was examined, the data provided unique support for the spillover
      model. Implications of the findings for both attachment and work family
      relationship literatures are discussed.

PMID- 11519650
TI  - Effects of trainer expressiveness, organization, and trainee goal orientation on
      training outcomes.
AB  - This laboratory experiment investigated the effects of trainer expressiveness,
      lecture organization, and trainee goal orientation on training outcomes.
      Participants (N = 135) listened to lectures that differed in organization and
      trainer expressiveness. Participants completed recall and problem-solving tests
      immediately and 2 days later. The results indicated that participants had the
      highest recall after an expressive and organized lecture. The findings for
      problem-solving performance were more complex. Participants with a high mastery
      orientation had their poorest problem-solving performance after listening to an
      organized and inexpressive lecture, whereas participants with a low mastery
      orientation did not respond to the effects of organization or expressiveness.

PMID- 11519651
TI  - A quantitative review of the guilty knowledge test.
AB  - The guilty knowledge polygraph test (GKT; D. T. Lykken, 1959, 1960) is a
      psychophysiological method of identifying suspects with concealed information
      about a crime. A meta-analysis of 50 treatment groups drawn from 22 laboratory
      simulation studies (total N = 1,247) was conducted to provide a comprehensive
      estimate of GKT accuracy under controlled conditions. Electrodermal measures
      correctly identified 76% of participants with concealed knowledge and 83% of
      those without information. Informed participants were detected at rates
      significantly in excess of chance, with a mean weighted effect size of .57.
      Enactment of mock crimes increased the hit rate to 82%. The rates of false
      positive error among noninformed treatment groups did not significantly exceed
      chance. Applications and research directions are discussed.

PMID- 11519652
TI  - The implications of linking the dynamic performance and turnover literatures.
AB  - This article examines how the literatures of dynamic performance and the
      performance-turnover relationship inform each other. The nonrandom performance
      turnover relationship suggests that dynamic performance studies may be biased by
      their elimination of participants who do not remain for the entire study period.
      The authors demonstrated that the performance slopes of those who leave an
      organization differ from the performance slopes of those who remain. This finding
      suggests that studies of the performance-turnover relationship need to consider
      employee performance trends when predicting turnover. Replicating and extending
      the research of D. A. Harrison, M. Virick, and S. William (1996), the authors
      found that performance changes from the previous month and performance trends
      measured over a longer time period explained variance in voluntary turnover
      beyond current performance. Finally, the authors showed that performance trends
      interacted with current performance in the prediction of voluntary turnover.

PMID- 11519653
TI  - Leader-member exchange and its dimensions: effects of self-effort and other's
      effort on relationship quality.
AB  - Two hundred thirty-two manager-subordinate dyads provided data on the effort
      expended toward the development of leader-member exchange (LMX) relationships,
      how such effort related to expectations about relationship quality, and
      intentions to exert future effort toward relationship development. For both
      managers and subordinates, higher quality LMX relationships were reported and
      expectations were met when the other member of the dyad put forth effort into
      relationship development. One's own higher effort coupled with lower effort by
      the other was associated with a lower quality LMX relationship. Examination of
      the 4 dimensions of LMX (R. C. Liden & J. M. Maslyn, 1998) revealed unique
      effects depending on the dimension considered. In addition, LMX and relationship
      tenure interacted, showing that future effort toward relationship development was
      greatest when individuals had been in higher quality relationships for longer
      periods of time.

PMID- 11519654
TI  - Interviewee coaching, preparation strategies, and response strategies in relation
      to performance in situational employment interviews: an extension of Maurer,
      Solamon, and Troxtel (1998).
AB  - Voluntary attendance at an interview coaching session was positively related to
      situational interview performance, controlling for job knowledge, motivation to
      do well, race, and sex of 213 candidates applying for promotion into several
      police and fire department jobs in a large city. Discrete preparation strategies
      (e.g., participation in study groups, participation in role-playing) were related
      to participation in coaching and also were related to interview performance
      beyond what could be accounted for by coaching participation, shedding some light
      on the potential efficacy of specific preparation strategies for enhancing
      success in situational interviews. Most notably, coaching attendance and
      preparation by interviewees were positively associated with a tendency to use
      strategies in the interview that enhanced the organization of interviewees'
      answers, and this organization was positively associated with performance in the
      interview.

PMID- 11519655
TI  - Top 1 in 10,000: a 10-year follow-up of the profoundly gifted.
AB  - Adolescents identified before the age of 13 (N = 320) as having exceptional
      mathematical or verbal reasoning abilities (top 1 in 10,000) were tracked over 10
      years. They pursued doctoral degrees at rates over 50 times base-rate
      expectations, with several participants having created noteworthy literary,
      scientific, or technical products by their early 20s. Early observed distinctions
      in intellectual strength (viz., quantitative reasoning ability over verbal
      reasoning ability, and vice versa) predicted sharp differences in their
      developmental trajectories and occupational pursuits. This special population
      strongly preferred educational opportunities tailored to their precocious rate of
      learning (i.e., appropriate developmental placement), with 95% using some form of
      acceleration to individualize their education.

PMID- 11519656
TI  - Use of situational judgment tests to predict job performance: a clarification of
      the literature.
AB  - Although situational judgment tests have a long history in the psychological
      assessment literature and continue to be frequently used in employment contexts,
      there has been virtually no summarization of this literature. The purpose of this
      article is to review the history of such tests and present the results of a meta
      analysis on criterion-related and construct validity. On the basis of 102
      coefficients and 10,640 people, situational judgment tests showed useful levels
      of validity (rho = .34) that were generalizable. A review of 79 correlations
      between situational judgment tests and general cognitive ability involving 16,984
      people indicated that situational judgment tests typically evidence relationships
      with cognitive ability (rho = .46). On the basis of the literature review and
      meta-analytic findings, implications for the continued use of situational
      judgment tests are discussed, particularly in terms of recent investigations into
      tacit knowledge.

PMID- 11519657
TI  - The dynamics of assessment center validity: results of a 7-year study.
AB  - The authors investigated temporal trends in the validity of an assessment center
      consisting of a group discussion and an analysis presentation exercise for
      predicting career advancement as measured by average salary growth over a 7-year
      period in a sample of 679 academic graduates. The validity of the overall
      assessment rating for persons with tenure of 7 years, corrected for initial
      differences in starting salaries and restriction in range, was .39. There was a
      considerable time variation in the validity of both the overall assessment rating
      and the assessment center dimensions. In accordance with findings from research
      in managerial effectiveness and development, the interpersonal effectiveness
      dimension became valid only after a number of years, whereas the firmness
      dimension was predictive in the whole period and increased with time. For
      comparison, validity trends for 2 types of interviews and a mental test were also
      studied.

PMID- 11519658
TI  - Conflict across organizational boundaries: managed care organizations versus
      health care providers.
AB  - This research examined conflicts that occur across organizational boundaries,
      specifically between managed care organizations and health care providers. Using
      boundary spanning theory as a framework, the authors identified 3 factors in the
      1st study (30 interviews) that influence this conflict: (a) organizational power,
      (b) personal status differences of the individuals handling the conflict, and (c)
      their previous interactions. These factors affected the individuals' behavioral
      responses or emotions, specifically anger. After developing hypotheses, the
      authors tested them in a 2nd study using 109 conflict incidents drawn from 9
      different managed care organizations. The results revealed that organizational
      power affects behavioral responses, whereas status differences and previous
      negative interactions affect emotions.

PMID- 11519659
TI  - Role conflict and ambiguity of CEOs in international joint ventures: a
      transaction cost perspective.
AB  - Insights from transaction cost economics were used to study the boundary
      conditions underlying the role conflict and ambiguity of 265 CEOs in Chinese
      based international joint ventures. Role conflict and ambiguity were lower when
      the contract between parents was more complete. Contract completeness fully
      mediated the effects of parent objective gap and parent formalization on role
      ambiguity but only partially so in the case of role conflict. Role conflict was
      lower when the foreign parent was dominant in the venture but higher when the
      local parent was dominant. Role conflict and ambiguity were inversely related to
      cultural distance. Neither construct had a detrimental effect on international
      joint venture performance. Implications for role theory are discussed.

PMID- 11519660
TI  - A synthetic validity approach to testing differential prediction hypotheses.
AB  - A new method is presented for conducting differential prediction analyses that
      makes it possible to test differential prediction hypotheses with adequate
      statistical power even when the sample size within a job or a job family is very
      small. This method, called synthetic differential prediction analysis, represents
      an application of the logic of synthetic validation to differential prediction
      analyses. The authors explain this new method and describe its application in a
      selection-system validation study conducted in a large organization.

PMID- 11519661
TI  - Examining the effects of work externalization through the lens of social identity
      theory.
AB  - This study examines whether dissimilarity among employees that is based on their
      work status (i.e., whether they are temporary or internal workers) influences
      their organization-based self-esteem, their trust in and attraction toward their
      peers, and their altruism. A model that is based on social identity theory posits
      that work-status dissimilarity negatively influences each outcome variable and
      that the strength of this relationship varies depending on whether employees have
      temporary or internal status and the composition of their work groups. Results
      that are based on a survey of 326 employees (189 internal and 137 temporary) from
      34 work groups, belonging to 2 organizations, indicate that work-status
      dissimilarity has a systematic negative effect only on outcomes related to
      internal workers when they work in temporary-worker-dominated groups.

PMID- 11519662
TI  - Justice, citizenship, and role definition effects.
AB  - A limitation of the organizational citizenship behavior (OCB) literature is that
      theory and empirical evidence suggest that some employees define OCBs as part of
      their job. A theoretical framework that addresses this problem is tested in this
      article. The framework focuses on 2 effects: a role enlargement effect (i.e.,
      employees with more favorable attitudes define OCB as inrole behavior, which, in
      turn, results in greater citizenship) and a role discretion effect (i.e., the
      relationship between employees' attitudes and their citizenship will be stronger
      among employees who define OCB as extrarole behavior). In tests of this framework
      with 2 independent samples of supervisor-subordinate dyads, role definitions were
      found to moderate several relationships between procedural justice and OCB,
      providing support for the role discretion effect. Implications for OCB theory and
      research are discussed.

PMID- 11519663
TI  - Effects of computer surveillance on perceptions of privacy and procedural
      justice.
AB  - Electronic workplace surveillance is raising concerns about privacy and fairness.
      Integrating research on electronic performance monitoring, procedural justice,
      and organizational privacy, the author proposes a framework for understanding
      reactions to technologies used to monitor and control employees. To test the
      framework's plausibility. temporary workers performed computer/Web-based tasks
      under varying levels of computer surveillance. Results indicated that monitoring
      job-relevant activities (relevance) and affording those who were monitored input
      into the process (participation) reduced invasion of privacy and enhanced
      procedural justice. Moreover, invasion of privacy fully mediated the effect of
      relevance and partially mediated the effect of participation on procedural
      justice. The findings are encouraging for integrating theory and research on
      procedural justice and organizational privacy.

PMID- 11519664
TI  - The role of folate in the prevention of neural tube defects: human and animal
      studies.

PMID- 11519665
TI  - Contribution of Joaquin Cravioto to the research on malnutrition and mental
      development.

PMID- 11519666
TI  - Nutrition and mental development.

PMID- 11519667
TI  - Lipids and neurodevelopement.

PMID- 11519668
TI  - Macronutrients and neurotransmitter formation during brain development.

PMID- 11519669
TI  - Monoamines and protein intake: are control mechanisms designed to monitor a
      threshold intake or a set point?
AB  - The concentration of TYR in brain changes directly with dietary protein content
      in the 0-10% PE range, but not higher. The effect is large: TYR concentrations
      rise as much as two- to threefold between 0% and 10% dietary protein content.
      This increase produces a clear stimulation of the rate of catecholamine
      synthesis, observed both for DA and NE, and notably in the hypothalamus, a brain
      area involved in appetite regulation. A similar relationship to chronic dietary
      protein intake may also exist for tryptophan and its neurotransmitter product,
      5HT. Because the natural diet of rats, the animal model most commonly used in
      such studies, typically contains between 6% and 14% protein, and may contain less
      under unfavorable environmental circumstances, rats in the wild may frequently
      operate on the portion of the protein intake curve producing maximal changes in
      brain TYR (and perhaps TRP) concentrations. If so, then the production of
      catecholamines and 5HT may be similarly affected. By such a scenario, the brain
      might receive information regarding the animal's success in acquiring adequate
      amounts of protein in its diet. A similar argument can also be made for monkeys
      in the wild, based on their dietary habits, and thus possibly for humans. From
      this perspective, animals are hypothesized to monitor/regulate their intake of
      protein based on a threshold, rather than a set-point model. This notion is not
      new or unique to amino acids. For example, one current notion of leptin action is
      that it serves as a signal for energy intake important during periods of
      deficiency, but not excess. More generally, given the primacy in nature of the
      need to acquire adequate amounts of food in order to survive and reproduce, and
      the difficulty in achieving this nutritional goal, it may be that appetite
      control mechanisms have evolved in nature to center more on attaining and
      exceeding adequacy than on maintaining intake around a set-point well in excess
      of adequacy.

PMID- 11519670
TI  - B vitamins, homocysteine, and neurocognitive function.

PMID- 11519671
TI  - Ontogeny of brain and cognition: relevance to nutrition research.

PMID- 11519672
TI  - Antioxidants and cognitive function.

PMID- 11519673
TI  - Deficiency and excess of iron in brain function and dysfunction.

PMID- 11519674
TI  - Successful aging and nutrition.

PMID- 11519675
TI  - Aging successfully: a genetic perspective.

PMID- 11519676
TI  - Immunopotentiation of a developed Salmonella enterica serotype enteritidis
      vaccine by thymulin and zinc in meat chicken breeders.
AB  - The humoral immunity, spleen and thymus weight indices, lymphocyte count in the
      thymus cortex, and granuloma diameter at vaccination sites were assessed in four
      differently immunopotentiated groups of meat chicken breeders. Breeders in the
      first two groups were given a killed Salmonella enterica serotype Enteritidis
      (SE) vaccine subcutaneously at 15 and 19 weeks of age. Breeders in the third and
      fourth groups were left unvaccinated. Breeders in the first group were further
      immunopotentiated with zinc and thymulin. Each bird in the first group was given
      the immunopotentiators intraperitoneally in a volume of 0.1 ml at intervals of 3
      days for a period of 3 weeks, starting at 15 weeks of age. At each time, each
      bird in the first group received thymulin (10 ng) and ZnCl2 (1 micromol/L), using
      a carboxymethyl cellulose carrier, totalling 90 ng thymulin and 9 micromol of
      ZnCl2 per bird. Each bird in the first three groups was challenged orally with
      6.7 x 10(6) cfu/ml of highly virulent SE organisms, at an age of 22 weeks. The
      first group, which had received zinc and thymulin, had the earliest and highest
      humoral immune response to SE (p<0.05). This was observed at 2 and 4 weeks after
      the first vaccination. In addition, the first group had the highest mean thymus
      weight index, and the highest mean lymphocyte count in the thymus cortex. No
      significant difference was observed between the first two vaccinated groups in
      the mean granuloma diameter developed at the two vaccination sites 48 h after
      administration of the vaccine (p>0.05).

PMID- 11519677
TI  - Evolution of fructosaminaemia and glucaemia during the growth of unweaned and
      early weaned half-bred zebu calves.
AB  - The purposes of the study were to obtain the confidence intervals for serum
      fructosamine concentrations in unweaned and early weaned calves, to verify the
      changes in this glycated protein during growth, when glucaemia declines, and to
      assess the changes in both parameters attributable to stress or alarm. Sixty out
      of 120 suckling half-bred zebu calves (60-75 days old) were weaned at day 0 and
      then received a commercial balanced diet, while the remainder continued to suck.
      Blood samples were taken at 0, 7, 14, 21, 28, 60, 90 and 120 days and the serum
      fructosamine and glucose concentrations were measured by conventional methods.
      Both biochemical parameters declined with time, but there were no statistical
      differences between the unweaned and weaned calves. The fall in fructosamine
      concentration correlated significantly with the decline in glucose concentrations
      in both groups. The confidence interval for fructosamine concentration decreased
      with age, from 294-303 micromol/L at 2 months old to 215-232 micromol/L at 6
      months old. At the same time, glucaemia declined from 7.5-8.6 mmol/L to 4.8-5.3
      mmol/L. Acute elevations in glucaemia, especially in the younger calves, were
      attributed to alarms, such as those caused by handling and blood extraction. The
      absence of resultant increases in fructosamine concentration discounts the
      existence of prolonged hyperglucaemias (stress) in early weaned calves.

PMID- 11519678
TI  - Pharmacokinetics of sulfadimethoxine and sulfamethoxazole in combination with
      trimethoprim after oral single- and multiple-dose administration to healthy pigs.
AB  - The pharmacokinetics were studied of sulfadimethoxine (SDM) or sulfamethoxazole
      (SMX) in combination with trimethoprim (TMP) administered as a single oral dose
      (25 mg + 5 mg per kg body weight) to two groups of 6 healthy pigs. The
      elimination half-lives of SMX and TMP were quite similar (2-3 h); SDM had a
      relatively long half-life of 13 h. Both sulfonamides (S) were exclusively
      metabolized to N4-acetyl derivatives but to different extents. The main metabolic
      pathway for TMP was O-demethylation and subsequent conjugation. In addition, the
      plasma concentrations of these drugs and their main metabolites after medication
      with different in-feed concentrations were determined. The drug (S:TMP)
      concentrations in the feed were 250:50, 500:100, and 1000:200 mg per kg. Steady
      state concentrations were achieved within 48 h of feed medication, twice daily
      (SDM+TMP) or three times a day (SMX+TMP). Protein binding of SDM and its
      metabolite was high (>93%), whereas SMX, TMP and their metabolites showed
      moderate binding (48-75%). Feed medication with 500 ppm sulfonamide combined with
      100 ppm TMP provided minimum steady-state plasma concentrations (C(ss,min))
      higher than the concentration required for inhibition of the growth of 90% of
      Actinobacillus pleuropneumoniae strains (n = 20).

PMID- 11519679
TI  - Inhibition of nitric oxide synthase with L-NAME does not increase lactate
      production at rest or during short-term high-intensity exercise in Thoroughbred
      horses.
AB  - The present study was carried out to determine whether inhibition of nitric oxide
      (NO) synthase promotes anaerobic metabolism in exercising horses, resulting in a
      significantly increased blood lactate concentration. N(omega)-nitro-L-arginine
      methyl ester (L-NAME) is a potent inhibitor of NO synthase that has been tested
      in horses and other species. Two sets of experiments, namely placebo (saline
      control) and L-NAME (20 mg/kg, i.v.) studies, were carried out on seven healthy,
      sound, exercise-trained, Thoroughbred horses in random order, 6 to 7 days apart.
      In both experiments, an incremental exercise protocol was used and data were
      obtained at rest, during submaximal exercise performed at 8 m/s on a 4.5% uphill
      grade, and during galloping at 14 m/s on a 4.5% uphill grade--a workload that not
      only elicited maximal heart rate and induced exercise-induced pulmonary
      haemorrhage, but also could not be sustained for more than 90 s. Measurements
      were also made in the recovery period. Mixed-venous blood samples, obtained at
      matched intervals in the two sets of experiments, were analysed in triplicate for
      determining the lactate concentration. Following administration of L-NAME,
      significant bradycardia occurred at rest (27 +/- 1 vs 37 +/- 2 beats/min in the
      placebo trials; p<0.0001) as well as during submaximal exercise (183 +/- 4 vs 200
      +/- 4 beats/min in the placebo trials; p<0.001), but the heart rate increased
      during galloping at 14 m/s on a 4.5% uphill grade to reach values observed in the
      placebo trials (215 +/- 2 beats/min) and significant differences were not found.
      At rest, the mixed-venous blood lactate concentration was similar in the two
      experiments. With exercise, the mixed-venous blood lactate concentration
      increased progressively as work intensity increased in both trials, but
      significant differences were not found between the placebo and the L-NAME
      experiments during submaximal exercise, near-maximal exercise or recovery. These
      experiments demonstrated that inhibition of NO synthase in Thoroughbred horses
      does not promote enhanced anaerobic metabolism at rest or during short-term
      incremental exercise leading to galloping at maximal heart rate.

PMID- 11519680
TI  - Bovine haematological values during fattening with possible implications for
      muscle growth.
AB  - Haemoglobin concentration (Hb), haematocrit (PCV) and mean corpuscular
      haemoglobin concentration (MCHC) were determined as indicators of oxygen-carrying
      capacity in 25 Simmental bulls during intensive fattening. Their possible
      relations to muscle growth were also investigated. The animals were the progeny
      of two sires. Blood samples were taken at 6, 9, 12 and 15 months of age. After
      slaughter, the right thoracic rib cut (7-9) was dissected into the longissimus
      dorsi muscle (LD), other muscles (OM) and total muscles (TM) (LD+OM). There was a
      significant increase in the mean PCV and Hb values during fattening. The PCV and
      Hb values were significantly correlated with the tissue share of OM or TM only at
      12 and 15 months of age. LD muscle share was not significantly correlated with
      any of the parameters at any fattening time. It would appear from these results
      that muscle growth proceeds in two phases. The first is until the age of 12
      months and the other from then to maturity.

PMID- 11519681
TI  - Tyrosine ameliorates some of the clinical, biochemical and haematological effects
      of acute stress associated with transportation of desert sheep.
AB  - We studied some clinical, biochemical and haematological variables in Desert
      (Najdi) sheep acutely stressed in the course of individual road transportation,
      and the influence thereon of pretreatment with tyrosine. Transportation for 30
      min resulted in variable but statistically insignificant increases in heart,
      pulse and respiratory rates. It also caused significant increases in the plasma
      concentration of cortisol (from 43.5 to 101.7 mmol/L) and glucose (from 3.1 to
      4.5 mmol/L), and a decrease in that of magnesium (from 0.85 to 0.72 mmol/L). The
      endogenous thiocyanate level was unaffected. The transportation stress also
      decreased the haematocrit (PCV) and the number of lymphocytes, and increased the
      concentration of haemoglobin. Pretreatment of sheep with tyrosine at a dose of
      100 mg/kg by the intravenous route significantly ameliorated the stress-induced
      clinical, biochemical and haematological changes. The treatment caused no overt
      adverse effects.

PMID- 11519683
TI  - Retinol values in the plasma of the Arabian camel (Camelus dromedarius) and the
      influence of aflatoxicosis.
AB  - The normal values are reported of the concentration of vitamin A (retinol) in the
      plasma of 44 male and female adult camels (Camelus dromedarius) in the United
      Arab Emirates. The concentrations of the vitamin in the plasma of eight camels of
      both sexes afflicted with aflatoxicosis were also determined. The mean
      concentration (+/-SD) of the vitamin in healthy camels was 460.1 +/- 49.3 ng/L.
      Sex had no significant effect on the concentration of the vitamin. Camels with
      aflatoxicosis had a mean concentration of retinol in the plasma of 243.4 +/- 32.3
      ng/L. The concentrations of aflatoxins in the liver and ruminal contents of these
      animals were 18.2 +/- 1.3 and 243.4 microg/kg, respectively.

PMID- 11519682
TI  - Fumonisin B1 metabolism by bovine liver microsomes.
AB  - Only limited and contrasting information is available about the metabolic fate in
      cattle of fumonisin B1, a mycotoxin produced by moulds of Fusarium. This study
      was carried out to evaluate the hepatic metabolism of fumonisin B1 by bovine
      liver microsomes. No biodegradation or metabolization of the mycotoxin by liver
      microsomes was detectable after incubating fumonisin B1 with bovine microsomes in
      the presence of a regenerating system for 1 h. No aminopolyol 1, aminopolyol 2 or
      aminopentol, metabolites of fumonisin B1, were detected in any of the incubated
      samples. The tolerance of ruminants to fumonisin B1 is apparently not dependent
      on its detoxification in the rumen.

PMID- 11519684
TI  - Rigid multilamellar bilayer cooperativity is modified by non covalently linked
      neuraminic-5-acid: a spectrophotometric determination.
AB  - By means of recording a simple serie of merocyanine 540 spectra, we present a
      method to calculate the value proportional to co-operative unit size of membranes
      (n). Our calculations, applied to different liposomal samples processed in the
      presence or absence of sugars, in high or low ionic strength showed two main
      results. First, that any temperature cycling in high ionic strength of rigid DPPC
      bilayers will modify the membrane cooperativity. Second, the presence of
      polysaccharide Neu-5-ac in solution will always produce a strong drop in co
      operativity of a rigid membrane of DPPC, whenever the negative charge is fully
      exposed. This last result indicates a differential ability of charged Neu-5-ac to
      disrupt a rigid membrane structure, even in the absence of a covalent linkage and
      -remarkably-in fully hydrated media.

PMID- 11519685
TI  - The effect of azalomycin F on Ca2+ homeostasis in Trichoderma viride and
      Saccharomyces cerevisiae.
AB  - Azalomycin F (AMF), a macrocyclic lactone antibiotic, in concentrations of 10(-5)
      g/ml (10(-6) - 10(-5) mol/l) was found to stimulate both the 45Ca2+ influx and
      efflux in intact Trichoderma viride submerged mycelium and in cells of
      Saccharomyces cerevisiae without having Ca2+ ionophoric properties. AMF also
      inhibited ATP-dependent Ca2+ uptake in membrane fractions prepared from T. viride
      submerged mycelium. 45Ca2+ which had been accumulated in membrane fractions in an
      ATP-dependent manner was released upon addition of AMF. This release was observed
      in light organellar fractions (LOF) of S. cerevisiae and of T. viride submerged
      mycelium and, to a small extent, in heavy organellar fraction (HOF) of S.
      cerevisiae. No Ca2+ releasing effect of AMF was observed in HOF from T. viride
      submerged mycelium. In S. cerevisiae expressing Ca2+-dependent photoprotein
      aequorin, AMF induced transients of luminescence which reflect changes in the
      cytoplasmic Ca2+ concentration. The results suggest that the stimulation by AMF
      of the Ca2+ efflux from the mycelium (cells) could be explained by an increase of
      the cytoplasmic Ca2+ concentration due to the release of Ca2+ from microsomal
      membranes or to the stimulation of Ca2+ influx.

PMID- 11519686
TI  - Glycoproteins present in the fraction of chromatin proteins loosely bound to DNA
      from hamster, chicken and frog liver cells.
AB  - There are numerous glycoproteins recognized by Concanavalin A (ConA) and
      Galanthus nivalis agglutinin (GNA) in 0.35 mol/l NaCl soluble fraction of
      chromatin proteins loosely bound to DNA from hamster, chicken and frog liver
      cells. Results of our detailed comparative analysis show a marked similarity
      between liver chromatin glycoproteins from the examined animals. The presence of
      similar chromatin glycoproteins in different animal species may indicate that
      they play an important universal role in the liver cells.

PMID- 11519687
TI  - Effects of silperisone on the excitation process in Ranvier nodes.
AB  - The effect of silperisone on single intact Ranvier nodes of the toad Xenopus was
      investigated by adding it to the bathing medium. At 100 micromol/l the following
      fully reversible effects were observed: 1. The spike amplitude decreased in a
      frequency-dependent manner. 2. Both the sodium activation and the inactivation
      curves as well as the potential dependence of taum were slightly shifted in the
      negative direction, while tauh did not change. 3. The sodium permeability
      constant PNa decreased by 50%. 4. The potassium currents acquired a phasic time
      course previously described for certain psoralens. They reached a relative
      maximum and then approached a lower steady state value, kappa(infinity) with a
      time constant of about 5 ms. Concentration-related responses of PNa, PK and of
      k(infinity), yielded: 5. The apparent dissociation constant of block of PNa was
      110 micromol/l. 6. PK proved not to be changed by silperisone in the
      concentration range tested, while the variable kappa(infinity) yielded a relation
      similar to that of PNa except that the apparent dissociation constant was 24
      micromol/l. The phasic course of the potassium currents in the presence of
      silperisone may be due to an open channel blockade. In view of the similarities
      between the actions of silperisone and 5-methoxypsoralen, it is entirely
      conceivable that silperisone has potential for an antispastic drug, e.g., in
      demyelinating diseases like multiple sclerosis.

PMID- 11519688
TI  - Luteinization factor-stimulated steroidogenesis in porcine granulosa cells.
AB  - Luteinization stimulator (LS), an intrafollicular compound of preovulatory (5-8
      mm) follicles, increased both the basal and gonadotropins-stimulated production
      of progesterone by immature (1-3 mm) granulosa cells. The mechanism by which LS
      enhance steroidogenesis was investigated by studying the modulation of
      progesterone biosynthesis from exogenous cholesterol and pregnenolone in cultured
      porcine granulosa cells in serum-free medium. Progesterone production by cultured
      granulosa cells was stimulated by FSH, while treatment with 22-OH-cholesterol
      further enhanced the gonadotropin action. The activity of LS was found in cell
      conditioned media obtained after 3-day cultivation of preovulatory granulosa
      cells. Conversion of 22-OH-cholesterol into progesterone by granulosa cells
      isolated from small follicles was significantly stimulated in the presence LS in
      culture media. Also, progesterone production by granulosa cells in the presence
      of pregnenolone was increased considerably. Concomitant treatment with LS led to
      a further augmentation in progesterone synthesis. Endogenous formation of
      pregnenolone was inhibited by aminoglutethimide. Thus, LS enhancement of
      progesterone production in cultured porcine granulosa cells is associated with an
      increase in the activity of cytochrome P450 cholesterol side-chain cleavage and
      3beta hydroxysteroid dehydrogenase enzymes.

PMID- 11519689
TI  - Small-angle neutron scattering study of N-dodecyl-N,N-dimethylamine N-oxide
      induced solubilization of dioleoylphosphatidylcholine bilayers in liposomes.
AB  - Mixtures of N-dodecyl-N,N-dimethylamine N-oxide (DDAO) and 1,2
      dioleoylphosphatidyl choline (DOPC) in chloroform/methanol were evaporated, dried
      and hydrated in excess 2H2O. Aqueous dispersions thus prepared were extruded
      through polycarbonate filter with pores of diameter 500A. These samples were
      studied using small-angle neutron scattering. DDAO destabilizes the bilayer in
      unilamellar liposomes and solubilizes it into mixed micelles whose shape changes
      with the DDAO : DOPC molar ratio. Bilayers or/and bilayer fragments have been
      observed up to DDAO : DOPC = 1.5, rod-like particles (tubular, cylindric
      micelles) at 2.5 < DDAO : DOPC < 3.5, and transition to globular particles
      (spheroid micelles) at DDAO: DOPC > 4. In bilayers or/and bilayer fragments, DDAO
      modulates the thickness of the bilayer.

PMID- 11519690
TI  - Modification and quantitative analysis of the Munch model in the integrated
      system of water translocation in plants.
AB  - Aiming at making the Munch model more adequate to the biological reality we
      introduce certain modifications and complements. Considering the model within the
      framework of so-called integrated system of long-distance water transport in
      plants we present a quantitative analysis based on the Kedem-Katchalsky
      formalism. A new mathematical description of the reverse osmosis is also
      utilized. The work is a starting point for further quantitative studies and
      simulations of the phloem transport of water and assimilates in plants.

PMID- 11519691
TI  - Separation of low molecular weight proteins with SDS-PAGE using taurine as a new
      trailing ion.
AB  - Taurine as an alternative trailing ion for tricine yields an identical resolution
      but reduces the running time by 15% and the power consumption by 15% compared to
      tricine. Therefore cooling of gels is more effective in SDS PAGE with taurine and
      artefacts due to oxidation of proteins can thus be reduced.

PMID- 11519692
TI  - Immunodetection of noncollagenous matrix proteins during periodontal tissue
      regeneration.
AB  - The interface between denuded dentin and regenerative periodontal tissue was
      investigated in a rat alveolar bone defect model using morphological and
      immunocytochemical approaches. The dentin surface was surgically exposed along
      the palatal roots of maxillary first molars. At 3 weeks post treatment, animals
      were perfused and treated regions from decalcified mandibles were embedded in
      Epon for ultrastructural studies or LR White for post-embedding immunogold
      labeling. Thin tissue sections were incubated with antibodies against
      noncollagenous matrix (osteopontin, bone sialoprotein, osteocalcin and
      fibronectin) and plasma (alpha2HS-glycoprotein and albumin) proteins. While in
      some cases, regenerative events took place directly on the denuded dentin
      surface, the interface between the denuded dentin and regenerating periodontal
      tissue was frequently characterized by the presence of an interfacial zone. This
      zone sometimes showed an electron-dense, cement line-like, planar accumulation of
      organic material immunoreactive for osteopontin and bone sialoprotein.
      Immunolabeling for osteocalcin and alpha2HS-glycoprotein was moderate and diffuse
      throughout the interfacial zone, whereas labeling with antibodies to albumin and
      fibronectin resulted in a weak reaction. It is concluded that accumulation of
      bone sialoprotein and osteopontin is a primary event during the formation of
      regenerative cementum onto denuded root surfaces.

PMID- 11519693
TI  - Phenotypical and functional analysis of T cells in periodontitis.
AB  - To explore aspects of cellular immune responses in the pathogenesis of
      periodontitis we analyzed phenotype and function of peripheral T cells. Two
      groups of subjects participated: one group consisted of 10 highly susceptible
      patients with severe periodontitis (mean age 29 years) and a control group
      consisted of 10 age, gender and race matched subjects with gingivitis. From all
      subjects peripheral blood was collected. The results showed that the numbers of
      CD3+, CD4+ and CD8+ T cells as well as the CD4/CD8 ratio, and the proliferative
      capacity of T cells, were not different between the two groups of subjects. Also,
      proportions of naive and memory T cells for both the CD4+ and CD8+ subpopulations
      were not different. Functional heterogeneity within the CD4+ and CD8+ T cell
      compartments was determined by intracellular analysis of interferon-gamma (IFN
      gamma) and interleukin-4 (IL-4) production. On the basis of these latter analyses
      among CD4+ and CD8+ cells, T helper (Th) 1 or Th2 function and T cytotoxic (Tc) 1
      or Tc2 function, respectively, could be deduced. No significant differences in
      proportions of CD4+ and CD8+ T cells positive for intracellular IFN-gamma or IL-4
      were observed between periodontitis patients and gingivitis controls; however a
      higher level of intracellular IL-4 in CD8+ T cells was seen in periodontitis
      patients. This might indicate that there is a shift towards a Tc2 function within
      the CD8+ T cell subpopulation. The current explorative study suggests that
      further research into the role of CD8+ T cells in the pathogenesis of
      periodontitis is warranted.

PMID- 11519694
TI  - The acute effects of smokeless tobacco (snuff) on gingival blood flow in man.
AB  - Snuff-induced blood flow responses in the gingiva were evaluated in 22 healthy
      casual consumers of tobacco. Laser Doppler flowmetry (LDF) was used to measure
      blood flow simultaneously and continuously on two gingival sites (buccal aspect
      of the papillae between the upper lateral incisors and canines). In addition,
      measurements of skin blood flow in the forehead and palmar side of the left thumb
      were performed. Arterial blood pressure (BP) and heart rate (HR) were also
      recorded. Unilateral application of commercial snuff (500 mg, 1%) caused a marked
      and rapid increase in gingival blood flow (GBF) on the exposed side (p < 0.001).
      Blood flow increased also in the contralateral gingiva and forehead skin (p <
      0.05). Skin blood flow in the thumb showed an insignificant decrease. BP and HR
      increased. Vascular conductance increased significantly in the snuff-exposed
      gingiva but not in the contralateral gingiva or the forehead. Vascular
      conductance was largely unaffected in the thumb. It is concluded that acute
      application of snuff, besides giving rise to typical changes in BP and HR,
      increases GBF in and around the exposed area, probably through activation of
      sensory nerves and the subsequent release of vasodilatory peptides from their
      peripheral endings. Blood flow in unexposed gingival and forehead skin may
      increase probably due to humoral or nervously mediated mechanisms. However, a
      passive pressure-induced hyperaemia in the unexposed gingiva and forehead skin
      can not be excluded.

PMID- 11519695
TI  - Humoral immune response in early-onset periodontitis: influence of smoking.
AB  - Sixty-five patients with generalised early-onset periodontitis (G-EOP) (age range
      16-42 years, 32 smokers and 33 non-smokers) were assessed for antibody titres and
      avidity to a panel of five suspected periodontal pathogens (Porphyromonas
      gingivalis, Actinobacillus actinomycetemcomitans, Prevotella intermedia,
      Treponema denticola and Bacteroides forsythus). Thirty-four of these patients
      were untreated (17 smokers and 17 non-smokers), and thirty-one were in the
      maintenance phase of periodontal therapy (15 smokers and 16 non-smokers).
      Previous studies have investigated the effect of smoking on IgG levels in
      periodontitis patients in the context of the more extensive periodontal
      destruction seen in smokers. Based on this literature our hypothesis was that
      smokers would have depressed serum IgG levels directed against recognised
      periodontal pathogens compared with non-smokers. Antibody titres were measured by
      ELISA deploying fixed whole cells as coating. The IgG response was detected with
      biotin-anti-human IgG and avidin-peroxidase; avidity was determined by elution
      with ammonium thiocyanate. Median titres to A. actinomycetemcomitans, P.
      intermedia and T. denticola were significantly lower in maintenance patient
      smokers (p= 0.02, 0.02 and 0.002 respectively) but not in untreated patients.
      Avidity to P. gingivalis was also lower in smoking maintenance patients (p =
      0.003) but not in untreated patients. These findings may imply some interruption
      of immune maturation in smokers following periodontal treatment.

PMID- 11519696
TI  - A fluorometric microassay for histamine release from human gingival mast cells.
AB  - Mast cells are important effector cells of the immune system. We describe a rapid
      and inexpensive microassay to determine histamine release from human gingival
      mast cells. The assay is based on the coupling of histamine with o-phthalaldehyde
      (OPT) at a highly alkaline pH to form a fluorescent product. Using this assay
      with a sample volume of 10 microl/well in a 384 black well microplate, the
      histamine detection limit was 0.031 microg/ml. The human mast cell line (HMC-1)
      and fresh mast cells isolated from human gingival tissue (n = 10) were stimulated
      with substance P, anti-IgE or calcium ionophore A23187. Calcium ionophore
      significantly increased histamine release from HMC-1 cells and gingival mast
      cells (p < 0.05). This microassay will facilitate the study of mast cell
      histamine release in diseased oral mucosa.

PMID- 11519697
TI  - Mixed infection of Porphyromonas gingivalis and Bacteroides forsythus in a murine
      abscess model: involvement of gingipains in a synergistic effect.
AB  - Several microorganisms including Porphyromonas gingivalis and Bacteroides
      forsythus have been implicated to be etiologically important agents of
      periodontal disease. In this study, we determined the ability of combinations of
      periodontopathogenic microorganisms to cause tissue destruction in a murine
      abscess model. Although all bacterial combinations used in this study produced
      larger abscesses than did monoinfection of each bacterium, the combination of P.
      gingivalis and B.forsythus showed a synergistic effect on abscess formation.
      Since these two bacteria have been frequently found together in lesions of
      periodontitis, these results suggest the significance of their co-infection in
      the progression of periodontitis. P. gingivalis produces extracellular and cell
      associated cysteine proteinases (gingipains) which appear to be involved in its
      virulence. The rgpA rgpB double and kgp mutants induced significantly smaller
      abscesses than the wild type. Moreover, the rgpA rgpB kgp triple (gingipain-null)
      mutant hardly showed lesion formation at all with the experimental conditions
      used in this study, indicating that these genes encoding gingipains are important
      for virulence of P. gingivalis. Mixed infection of these P. gingivalis mutants
      with B. forsythus showed an additive effect on abscess formation, indicating that
      the gingipains of P. gingivalis may play an important role in the pathological
      synergism between P. gingivalis and B. forsythus.

PMID- 11519698
TI  - Effects of a bisphosphonate on the expression of bone specific genes after
      autogenous free bone grafting in rats.
AB  - The purpose of this study was to evaluate the clinical availability of a
      bisphosphonate in autogenous free bone grafts. Bisphosphonate (0.01 mg/kg/day)
      was administered daily after an autogenous free bone graft on a rat calvarium.
      The effects of a bisphosphonate on the resorption of grafted bone and mRNA
      expression in bone specific genes, i.e. bone morphogenetic protein 2, bone
      morphogenetic protein 4, alkaline phosphatase, osteocalcin, osteoclast inhibitory
      factor and calcitonin receptor, were studied via a reverse transcription
      polymerase chain reaction (RT-PCR), real time RT-PCR and tartrate-resistant
      alkaline phosphatase (TRAP) staining. In a clinical and histomorphological
      review, bone resorption decreased in the experimental group in contrast to the
      control group where active bone resorption was observed. Bisphosphonate altered
      not only the mRNA expression of the bone resorption associated genes but also the
      bone formation associated genes. The expression of the calcitonin receptor (CTR)
      mRNA was not detected and the osteoclast inhibitory factor (OCIF) was
      significantly up-regulated in the experimental group as opposed to the control
      group. The expressions of osteocalcin and alkaline phosphatase mRNAs were also
      higher in the experimental group. However, there was no significant difference in
      the mRNA expression of bone morphogenetic proteins between the two groups. The
      data suggest the possibility of a clinical application of bisphosphonates for
      decreasing resorption of grafted bone.

PMID- 11519699
TI  - Reduced dental plaque accumulation on composite gold alloy margins.
AB  - Restoration of tooth surfaces with materials that inhibit formation of heavy
      bacterial plaque accumulations could be important in the treatment of patients
      with existing oral disease or in reducing the likelihood for periodontal disease.
      Captek is a dental gold composite material used to produce copings for
      ceramometal restorations that has been reported to inhibit plaque accumulation.
      In this study, the oral bacteria of nine periodontally healthy subjects with a
      total of 42 gold composite copings were sampled. Contralateral teeth with normal
      tooth surfaces were also sampled as controls. The quantitative presence of forty
      bacteria was determined in each sample by DNA:DNA hybridization. The results
      indicated that the porcelain/gold composite alloy coping surfaces had
      significantly fewer bacteria than the control normal tooth surfaces (71%
      reduction). The percentage composition, however, did not differ significantly
      between surfaces.

PMID- 11519700
TI  - Patterns of cytokeratin expression in monkey and human periodontium following
      regenerative and conventional periodontal surgery.
AB  - The pattern of cytokeratin expression has been extensively described in the
      normal and inflamed periodontium. However, there is no information regarding the
      pattern of cytokeratin expression in the periodontium which has been reformed
      following regenerative periodontal surgery. The aim of the present investigation
      was to evaluate the pattern of cytokeratin expression in the reformed human and
      monkey periodontium following regenerative and conventional periodontal surgery.
      In 3 monkeys, acute fenestration-type and chronic intrabony defects were treated
      with guided tissue regeneration (GTR), enamel matrix proteins (EMD), or coronally
      repositioned flap surgery (control). After a healing period of 5 months, the
      animals were sacrificed and perfused with 10% buffered formalin for fixation.
      Specimens containing the defects and surrounding tissues were dissected free,
      decalcified in EDTA and embedded in paraffin. Histological sections were cut with
      the microtome set at 3 microm. The sections were alternatively stained either
      with hematoxylin and eosin, or immunohistochemically by using one of the broad
      range monoclonal antibodies 34betaE 12 (for cytokeratins 1, 5, 10 and 14) or KL 1
      (for cytokeratins 1, 2, 5, 6, 7, 8, 10, 11, 16 and 19), or one of the individual
      monoclonal antibodies LL025 (for cytokeratin 16), DC 10 (for cytokeratin 18), A53
      B/A2 (for cytokeratin 19). Twelve patients, each displaying one deep intrabony
      defect scheduled for extraction due to advanced periodontitis or prosthetic
      reasons, were treated as described above. Following a healing period of 6 months,
      the teeth were extracted together with some of their surrounding soft and hard
      tissues. The histological and immunohistochemical processing of the human
      biopsies was identical to that described in monkeys. The results revealed that
      both the normal non-treated (original) monkey and human junctional epithelium
      stained strongly with all of the monoclonal antibodies used. The reformed
      junctional epithelium displayed the same cytokeratin expression pattern as the
      non-treated junctional epithelium. No differences regarding the cytokeratin
      expression pattern of the junctional epithelium were found between the treatments
      and types of healing (i.e. regenerative, through a new periodontal ligament, or
      reparative through a long junctional epithelium). In the intact periodontal
      ligament, the epithelial rests of Malassez displayed a comparable cytokeratin
      expression pattern to that of the junctional epithelium. However, no expression
      of cytokeratins was seen in the newly formed periodontal ligament. In such
      specimens, cytokeratin expression was observed only until the borderline between
      the regenerated cementum and the epithelial downgrowth. It was concluded that: a)
      the reformed junctional epithelium, following any type of surgical procedure,
      displays a similar pattern of cytokeratin expression to the original junctional
      epithelium; b) in the newly formed periodontal ligament, no expression of
      cytokeratins is present; and c) the epithelial rests of Malassez do not seem to
      reform after regenerative periodontal surgery.

PMID- 11519701
TI  - Smoking and periodontal disease--perspectives.

PMID- 11519702
TI  - An evaluation of bone induction delivery materials in conjunction with root-form
      implant placement.
AB  - The success of bone-inductive cytokines in surgical alveolar defects is greatly
      dependent upon the ability of carrier materials to effectively deliver the
      inductive protein to the surgical site. An evaluation of three types of carrier
      materials was undertaken in six monkeys using an osseous defect of 2.0 cm that
      was produced by partial resection of the maxilla and mandible and placement of
      titanium implants in each alveolar quadrant. After 5 months, abutments were
      placed on the implants, which were allowed to function for an additional 5
      months. Intravital labeling with tetracycline was used to evaluate the late
      healing remodeling processes. The carriers were evaluated by studying (1) the
      amount of surface osseointegration on the root-form implants; (2) the bone
      density as related to trabecular pattern and cortex formation; and (3) the
      quantitative and qualitative thickness of the alveolar bone buccolingually at the
      implanted sites. Of the three materials, the calcium carbonate coral (BioCoral)
      produced a decreased amount of bone regeneration in comparison with both the
      poly(methylethyl methacrylate) material (HTR) and the porous bone mineral (Bio
      Oss). Both the HTR and Bio-Oss with rhBMP-2 produced excellent thickness of the
      repaired alveolar ridge. All three materials produced the same amount of
      osseointegration with the titanium implant surfaces. Good bone quality, as
      reflected in thickening of the trabecular bone patterns, was seen with both Bio
      Oss and HTR. While all three of these carrier materials appeared to produce good
      osseointegration with the titanium implants, BioCoral did not effect a
      quantitative or qualitative restoration of the alveolar bone comparable to that
      following the use of either HTR or Bio-Oss with rhBMP-2.

PMID- 11519703
TI  - Localized ridge augmentation using GBR and platelet-rich plasma: case reports.
AB  - Combining platelet-rich plasma (PRP) with autogenous bone graft materials has
      recently been advocated as a means of enhancing rate and quality of new bone
      formation in regenerative procedures. The aim of this case series was to evaluate
      the potential of PRP in combination with bone allograft to enhance bone
      regeneration in alveolar ridge defects exhibiting both vertical and horizontal
      loss prior to the placement of dental implants. Augmentation resulted in clinical
      and radiographic gains in both vertical and horizontal components of the osseous
      defects, thereby facilitating subsequent placement of dental implants. Histologic
      evaluation of the cases revealed the presence of residual allograft particles
      surrounded by connective tissue as well as newly formed bone within the grafted
      areas. However, the addition of PRP did not appear to enhance the quality or
      quantity of new bone formation over that reported in comparable guided bone
      regeneration (GBR) studies without PRP.

PMID- 11519704
TI  - Implant placement in three-dimensional grafts in the anterior jaw.
AB  - A series of 12 men and 13 women ranging in age from 24 to 71 years underwent two-
      or three-dimensional reconstruction of type C, D, or E ridges and placement of
      anterior implants. The mean horizontal augmentation was 6.4 mm (range 2 to 17
      mm), and the mean vertical augmentation was 4.22 mm (range 0 to 15 mm). The 67
      implants were all loaded, with the time averaging 34.4 months for the maxillary
      implants and 19 months for the mandibular implants. None of the implants have
      been lost to date. Two patients had flap retraction within the first 2 weeks that
      necessitated reapproximation. One patient had total failure of a J graft of iliac
      crestal bone from the maxillary left central incisor to canine starting 3 weeks
      after placement as the result of infection. The graft was removed at 6 weeks, and
      no implants were placed. Two patients suffered partial anterior graft loss, but
      their implants were successful in location and angulation. Implants and grafts
      can be combined with acceptable rates of complications and failure.

PMID- 11519705
TI  - Autogenous dental transplants: description of a clinical case.
AB  - The dental transplant was already in use more than 2,000 years ago, reaching a
      peak in the Middle Ages, but it was only after the 1950s that this subject
      appeared in the scientific literature. This article describes the case of a young
      woman whose mandibular left second and right first molars had to be extracted and
      were replaced using the maxillary third molars. The positive clinical and
      radiographic results over a 5-year period encourage the use of this technique.

PMID- 11519706
TI  - Treatment behavior and complete-mouth rehabilitation using AGC crowns: a case
      report.
AB  - This case report covers the combined functional and perioprosthetic complete
      mouth rehabilitation of a 67-year-old patient with severe temporomandibular joint
      pain caused by a prognathic forced incorrect centric relation and severe
      overclosure. Once bite guard treatment had been concluded and the pain had
      subsided completely, AGC electroformed crown and bridgework was fabricated.
      Electroformed crown-and-bridge copings exhibit extremely high precision of fit
      and, from the clinical point of view, perfect esthetics. As the coping material
      is pure gold and there are no bonding oxides in the gold-porcelain bonding layer,
      AGC restorations are readily integrated into the biologic structures around the
      crown margins. Perfectly healthy, noninflamed soft tissues, a lack of bluish
      livid colored gingival margins, and visible gingival reattachment around the
      crown margins are considerable benefits from the perioprosthetic point of view.
      This leads to foreseeable clinical success and promises further use of
      electroformed porcelain restorations.

PMID- 11519707
TI  - The influence of plaque and/or excessive loading on marginal soft and hard tissue
      reactions around Branemark implants: a review of literature and experience.
AB  - High implant survival rates are published with more than 15 years of observation
      time. Failures over time are often caused by ongoing marginal bone loss.
      Therefore, the need for reliable monitoring of the stability of periimplant
      attachment and/or bone level is extremely important. Marginal bone loss around
      osseointegrated implants has often been associated with periimplantitis, but
      clinical observations cannot prove this relationship. Otherwise, the impact of
      excessive loading on periimplant bone has been shown in animal studies and has
      been positively related to implant failure in terms of implant mobility and
      marginal bone loss. Some clinical observations support this hypothesis.

PMID- 11519708
TI  - Efficacy of porous bovine bone mineral in various types of osseous deficiencies:
      clinical observations and literature review.
AB  - Recent developments in osseous regenerative techniques have increased the demand
      for bone-substitute grafting materials. Porous deproteinized bovine bone mineral
      (PBBM), a biocompatible xenograft, has been used in different osseous
      deficiencies prior to or in conjunction with the placement of titanium implants.
      The different PBBM applications in fresh extraction sites, anatomic defects, and
      subantral floor elevation techniques are described. The use of an occlusive
      barrier membrane to regenerate bone via guided tissue regeneration principles was
      determined for each patient by clinical parameters. PBBM was well amalgamated and
      incorporated with the augmented hard tissue, but the transition between
      preexisting bone and the newly regenerated bone-like tissue was distinguishable
      by clinical examination even after 12 months. Grafted material was also
      identified using follow-up radiographs. In the presented cases, PBBM showed
      clinically satisfactory results as a biocompatible filler in bone augmentation
      procedures.

PMID- 11519709
TI  - Effect of early exposure on the integration of dental implants: Part 2--Clinical
      findings at 6 months postloading.
AB  - Implant exposure during initial healing after placement has been considered
      important in both implant integration and postloading effects. This study
      evaluated the effect of early implant exposure on the clinical findings
      prerestoration and 6 months postrestoration. Forty-eight implants (24 CPTi and 24
      Ti-13-13) were placed in maxillary and mandibular posterior sites in six baboons.
      Implant exposure was evaluated for 24 of the submerged implants at placement and
      at each weekly visit for 3 weeks after implant placement. The crestal bone level
      at maxillary posterior sites was measured at 6-month uncovering, and mandibular
      sites were measured at 3-month uncovering. All sites were again measured 6 months
      after restoration placement. Periotest readings were recorded at implant
      uncovering and again 6 months postloading. Arbitrary groupings of the Periotest
      values were assigned as good = -7 to -1; guarded = 0 to +2; and poor = +3 to +27.
      At 6 months postloading, there were no statistical differences between CPTi and
      Ti-13-13 for change in crestal bone height in either arch. The mean change in
      maxillary crestal bone height varied from a 0.59- to 1.35-mm loss. The
      differences between the mean exposed and nonexposed changes were not
      statistically significant The mean change in mandibular crestal bone height
      varied from a 0.25- to 0.88-mm loss. Changes in crestal bone height for
      nonexposed sites from 3-month implant uncovering to 6 months postloading were
      statistically significant at the mesial, buccal, and lingual aspects. The mean
      change for the nonexposed distal aspect approached significance. The differences
      between the mean exposed and nonexposed changes were not statistically
      significant. The overall percentage of maxillary implants in the good category
      for nonexposed sites decreased by 41% from uncovering to 6 months after loading,
      while no change occurred for exposed sites; the percentage of implants in the
      good category was comparable for early exposed and nonexposed sites (57% and 59%,
      respectively). At 6 months after loading, the percentage of implants in the good
      category was more favorable for early exposed (88%) than nonexposed sites (50%).
      A one-stage implant approach should provide similar postloading clinical results
      as the two-stage surgical approach.

PMID- 11519710
TI  - Continuing education.

PMID- 11519711
TI  - National Board fees: historical and comparative perspectives.

PMID- 11519712
TI  - The ocular and visual characteristics of an athletic population.
AB  - BACKGROUND: Nine hundred and thirty-nine athletes of various ages and from
      varying levels of competition were part of a sports vision epidemiology project
      conducted by the Sports Vision Service at the Illinois Eye Institute, Chicago,
      Illinois. METHODS: Data were collected from sports vision screenings conducted
      from 1992 to 1995. The population consisted of participants in the 1994 and 1995
      AAU Junior Olympic Games, members of the DePaul, Elmhurst, Illinois and College
      of DuPage athletic departments, and members of two local high school basketball
      programs, DuSable and Dunbar. The data collected were analyzed to determine the
      use of eye care services and the visual characteristics present in these elite
      athletic populations. RESULTS: Analysis of the data showed that athletes
      competing at high levels of competition do have visual problems. Twenty five
      percent of our population had never had a complete eye examination, 29% had
      visual symptoms, and 28% had less than 20/25 acuity through their habitual sports
      prescription. CONCLUSIONS: The results of this study imply that the athletic
      populations at all levels are in need of eye care services. Protective eyewear is
      not often used in this athletic population. Comparing the results found in our
      population to other reported results in the general population indicate similar
      rates of refractive error.

PMID- 11519713
TI  - Nonprescription tinted eyewear optical accuracy study.
AB  - BACKGROUND: Nonprescription tinted eyewear, commonly referred to as noncorrective
      sunglasses or plano sun eyewear, often induce measurable amounts of prismatic
      deviation. With high-wrap eyewear this effect becomes more pronounced. The
      purpose of this project was to assess the amount of horizontal and vertical
      prismatic deviation induced by some popular premium plano sun eyewear intended
      for use by athletes. METHODS: Prismatic deviations for two identical pairs of
      high-wrap, steep base curve, plano sun eyewear from each of six prominent
      national brands were measured in both primary gaze and along a peripheral line of
      sight 30 degrees to the right of straight-ahead. RESULTS: Most of the eyewear
      induced base-out and base-down prism in each lens in primary gaze. All eyewear
      induced base-in prism with temporal gaze and base-out prism with nasal gaze at 30
      degrees laterally. Most eyewear induced base-down prism with lateral gaze as
      well. CONCLUSIONS: Plano sun eyewear is often purchased for use in bright
      environments during visually demanding sports, such as golf, baseball, and
      volleyball. It is well-documented that athletes possess superior visual function
      as compared to nonathletes or lesser-level athletes. Further studies are
      indicated to determine the impact of this prism on the average wearer and the
      elite athlete.

PMID- 11519714
TI  - A comparison of patient reading performance and preference: optical devices,
      handheld CCTV (Innoventions Magni-Cam), or stand-mounted CCTV (Optelec Clearview
      or TSI Genie).
AB  - BACKGROUND: Clinicians frequently prescribe reading devices for low vision
      patients having a central field loss. This study seeks to provide comparative
      information the clinician can use to assist patients in selecting the most cost
      effective device(s) for reading. METHOD: In this study we compared optical
      devices with two types of closed-circuit televisions (CCTVs) that differed in two
      important characteristics: price, and whether the camera was stand-mounted with
      an X-Y table or whether the camera was handheld. A "within-subjects" design was
      used with 22 subjects. The primary comparisons between devices were subject
      reading speed, duration, and preference. RESULTS: Subject reading speed and
      duration were significantly greater with the CCTV systems than with optical
      devices; however, no significant performance differences were found between the
      two types of CCTVs. Patients did express a clear preference for one versus the
      other type of CCTV, with an overall preference for the stand-mounted system. When
      asked to consider the price differential between types of CCTVs, patient
      preferences were about equally divided. CONCLUSIONS: Clinicians can expect
      significantly better initial reading performance for patients with central visual
      field losses when reading with CCTVs versus optical devices. Handheld CCTVs, when
      compared with stand-mounted systems, are less expensive, provide equal
      performance, and have slightly lower subject preference ratings. The current
      study provides clinicians with objective performance data and subjective
      preference data that can be used to help patients with central visual-field
      losses select the most cost-effective reading device.

PMID- 11519715
TI  - HIPAA privacy rules: what they are and what they mean for optometrists.

PMID- 11519716
TI  - A question of privacy.

PMID- 11519717
TI  - Synthesis and characterization of N,N-dichlorinated amino acids: taurine,
      homotaurine, GABA and L-leucine.
AB  - Epilepsy, trauma and other circumstances leading to hyperexcitable conditions in
      the CNS tend neurochemically to be associated with excessive stimulated release
      of glutamic acid and/or a failure of GABA modulated inhibition. Somewhat to a
      lesser extent, taurine and its homologue homotaurine, have also been shown to
      antagonize the excitatory actions of glutamic acid. Here we report the successful
      synthesis and isolation in pure form of N,N-dichlorinated GABA, taurine,
      homotaurine and leucine. These compounds are much more lipophilic than their
      parent compounds and may therefore more readily penetrate the blood-brain barrier
      systems into the neural tissue, where they can be easily dechlorinated. Very
      preliminary biological testing shows that this may indeed occur. The synthesis
      and purification methodology will likely also be applicable to a number of other
      amino acids as well as certain peptides or selected proteins.

PMID- 11519718
TI  - Distribution of glutamate receptors of the NMDA subtype in brains of heterozygous
      and homozygous weaver mutant mice.
AB  - In weaver mice, mutation of an G-protein inwardly rectifying K+ channel leads to
      a cerebellar developmental anomaly characterized by granule and Purkinje cell
      loss and, in addition, degeneration of dopaminergic neurons. To evaluate other
      deficits, glutamate receptors sensitive to N-methyl-D-aspartate (NMDA) were
      examined by autoradiography with [3H]MK-801 in 36 brain regions from heterozygous
      (wv/+) and homozygous (wv/wv) weaver mutants, and compared to wild type (+/+)
      mice. In wv/+ and wv/wv mutants labelling decreased in cortical regions, septum,
      hippocampus, subiculum, neostriatum, nucleus accumbens, superior colliculus and
      in the cerebellar granular layer. The reductions in [3H]MK-801 binding were
      particularly specific in the cerebellar granular layer of wv/wv mutants, but an
      ubiquitous altered NMDA receptor topology was revealed in other brain regions.
      Abnormal developmental signals, or aberrant cellular responses, may underlie
      widespread NMDA receptor reductions, while in cerebellar cortex they could be
      lacking due to the massive loss of cerebellar granule cells.

PMID- 11519719
TI  - Effects of neonatal hypoxia/ischemia on ganglioside expression in the rat
      hippocampus.
AB  - Neonatal Hypoxia-Ischemia (HI) triggers a cascade of biochemical events that
      result in neuronal injury, but the mechanisms underlying these processes are not
      completely understood, and information regarding the effect of HI on the
      synthesis of brain glycoconjugates is lacking. The present work evaluates the
      effects of neonatal HI on hippocampal ganglioside synthesis. Seven-day-old rat
      pups were exposed to HI for 2.5 h according to the modified Levine model and
      samples from hyppocampus were obtained at 30 min as well as at 1, 2 and 4 days
      later. The activity for synthesis of gangliosides was evaluated by determining
      the incorporation of N-acetyl [3H]neuraminc acid ([3H]NeuAc) into the endogenous
      gangliosides of Golgi membranes and by determining the activity of Sial-T2 (GD3
      synthase) and GalNAc-T (GM2 synthase), the two enzymes acting on
      sialyllactosylceramide (GM3) at the branching point of synthesis of a- and b
      ganglioside pathway. Northern blot experiments were also conducted to determine
      transcription levels of the mRNAs specific for these transferases. Neonatal HI
      caused a relative increase of in vitro [3H]NeuAc incorporation into endogenous
      lactosylceramide, which was most noticeable at 30 min and I day post-event and
      disappeared by day 2 and 4. The transient accumulation of [3H]GM3 correlated with
      decreases in the activities of GD3- and GM2 synthase measured at 30 min and at 1
      day after the HI insult. No significant variations in the expression of the genes
      for these enzymes were observed. Results suggest that transient accumulation of
      GM3 may be due to post-translational events negatively modulating both GD3- and
      GM2 synthase activities.

PMID- 11519720
TI  - Functional analysis for peripheral myelin protein PASII/PMP22: is it a member of
      claudin superfamily?
AB  - Two major glycoproteins, P0 and PASII/PMP22, are specifically expressed in
      peripheral myelin. Point mutations of these proteins and over or under expression
      of PASII/PMP22 cause various hereditary peripheral neuropathies. P0 is well
      characterized as a major adhesion molecule in PNS myelin, but the function of
      PASII/PMP22 is still unknown. Recently, an oligodendrocyte-specific protein (OSP)
      was identified as a member of the claudin family and as a component of tight
      junctions of central myelins. Since PASII/PMP22 shows similarity in structure to
      OSP, which is a tetraspan membrane protein, we speculated if PASII/PMP22 could be
      a member of claudin superfamily. The primary structure of PASII/PMP22 showed a
      significant homology of 48% and a 21% identity with the OSP sequence. Exogenous
      expression of PASII/PMP22 in C6 cells significantly inhibited BrdU incorporation
      to the cells. The C6 cells stably transfected with PASII/PMP22 cDNA showed no
      homophilic cell adhesive activity. When dorsal root ganglion (DRG) neurons were
      cocultured on PASII/PMP22 expressing cells, both neurite extension and branching
      of DRG neurons were significantly inhibited. These results indicate that
      PASII/PMP22 may play a role in a turning point of Schwann cell development from
      proliferation to differentiation. On the other hand, the cells expressing claudin
      family proteins are reported to show strong cell adhesive activity and an ability
      to form tight junctions with neighboring cells. For this reason, we currently do
      not have any functional data supporting that PASII/PMP22 is the member of claudin
      superfamily.

PMID- 11519721
TI  - Differences in nicotine-induced dopamine release and nicotine pharmacokinetics
      between Lewis and Fischer 344 rats.
AB  - Studies have shown a greater preference for the self-administration of drugs such
      as nicotine and cocaine in the Lewis rat strain than in the Fischer 344 strain.
      We examined some factors that could contribute to such a difference. The baseline
      level of extracellular dopamine in nucleus accumbens shell was about 3-times
      higher in Fischer rats than in Lewis rats (3.18 +/- 0.26 vs. 1.09 +/- 0.14 pg/
      sample). Nicotine (50-100 microg/kg)-induced release of dopamine, expressed in
      absolute terms, was similar in the two strains. Dopamine release expressed in
      relative terms (as percent of baseline), however, was significantly greater in
      Lewis rats than in Fischer rats at 30 min after the first nicotine injection. We
      suggest that the relative increase is of more influence than the absolute level
      for determining preference; a lower physiological extracellular dopamine level
      thus represent a risk factor for increased preference. Amphetamine-induced
      dopamine release expressed in relative terms was not greater in the Lewis strain.
      In the initial time period of the microdialysis experiments, a sharper peak in
      nicotine-induced accumbal dopamine release in Lewis and a less but more sustained
      release in Fischer rats was observed. This release pattern paralleled the faster
      clearance of nicotine from blood of Lewis compared to Fischer rats. In tissue
      slices the electrically induced dopamine release was highest in the nucleus
      accumbens and lowest in the ventral tegmentum. A significant effect of nicotine
      was lowering the electrically induced release of dopamine in frontal cortex
      slices from Fischer brain and increasing this dopamine release in the ventral
      tegmentum of Lewis brain slices indicating that the ventral tegmentum, an area
      controlling dopamine release in the accumbens, is more responsive to nicotine in
      the Lewis rat. Nicotine levels tended to be more sustained in Fischer rats in
      different brain regions, although the difference in nicotine levels between the
      strains was not significant at any time period. Several factors contribute to
      nicotine preference, including the endogenous dopamine level, and the sensitivity
      of ventral tegmentum neurons to nicotine-induced dopamine release. Strain
      differences in pharmacokinetics of nicotine may also play a role.

PMID- 11519722
TI  - Remyelination in vitro following protein kinase C activator-induced
      demyelination.
AB  - In previous work we found that mezerein, a C kinase activator, as well as basic
      fibroblast growth factor (FGF-2) induce demyelination and partial oligodendrocyte
      dedifferentiation in highly differentiated aggregating brain cell cultures. Here
      we show that following protein kinase C activator-induced demyelination,
      effective remyelination occurs. We found that mezerein or FGF-2 caused a
      transient increase in DNA synthesis following a pronounced decrease of the myelin
      markers myelin basic protein and 2',3'-cyclic nucleotide 3'-phosphohydrolase.
      Both oligodendrocytes and astrocytes were involved in this mitogenic response.
      Within 17 days after demyelination, myelin was restored to the level of the
      untreated controls. Transient mitotic activity was indispensable for
      remyelination. The present results suggest that myelinating oligodendrocytes
      retain the capacity to reenter the cell cycle, and that this plasticity is
      important for the regeneration of the oligodendrocyte lineage and remyelination.
      Although it cannot be excluded that a quiescent population of oligodendrocyte
      precursor cells was present in the aggregates and able to proliferate,
      differentiate and remyelinate, we could not find evidence supporting this view.

PMID- 11519723
TI  - Mutant Plp/DM20 cannot be processed to secrete PLP-related oligodendrocyte
      differentiation/survival factor.
AB  - Most of the mutations within the PLP gene result in degeneration of
      oligodendrocytes and this is believed to be caused by intracellular trafficking
      defects. Previous studies have demonstrated that cells expressing the wild type
      PLP gene release a factor promoting differentiation/survival of oligodendrocyte
      and that this factor is the C-terminal portion of the protein itself. In this
      study we asked how the naturally occurring mutations of the PLP gene (jimpy,
      jimpy msd, and rumpshaker) affect this activity. We developed a transient
      expression system for retroviral production and transduction that enabled the
      expression of mutant PLP/DM20 cDNAs in NIH3T3 cells. None of the NIH3T3 cells
      producing mutant PLP/DM20s secreted the PLP-related factor that increases the
      number of oligodendrocytes. Since it has been shown that rumpshaker DM20 can be
      transported to the cell surface, but its folding is incorrect, absence of
      secretion of this factor is more heavily attributable to incorrect protein
      folding than to the defect in the PLP/DM20 trafficking.

PMID- 11519726
TI  - Psychosine is as potent an inducer of cell death as C6-ceramide in cultured
      fibroblasts and in MOCH-1 cells.
AB  - Cytotoxic capacity of psychosine (galactosylsphingosine) was evaluated in
      comparison with C6-ceramide in cultured fibroblasts and the glia-derived MOCH-1
      cells that have characteristics of myelinating cells (1). Psychosine caused
      cytotoxic cell death and DNA fragmentation at concentrations similar to C6
      ceramide and MOCH-1 cells were substantially more sensitive to their cytotoxic
      effects than fibroblasts. In this system, pretreatment with GM1-ganglioside
      failed to protect the cells from the deleterious effects of these compounds.
      These findings are consistent with the hypothesis that psychosine is the
      cytotoxic metabolite that causes apoptotic death of the oligodendrocyte in
      globoid cell leukodystrophy (Krabbe disease). They further suggest that the
      protective capacity of GM1-ganglioside is unlikely to be the explanation for the
      paradoxical improvement of the phenotype of globoid cell leukodystrophy in the
      mouse simultaneously deficient in two lysosomal beta-galactosidases,
      galactosylceramidase and GM1-ganglioside beta-galactosidase.

PMID- 11519725
TI  - Comparison of effects of DL-threo-beta-benzyloxyaspartate (DL-TBOA) and L-trans
      pyrrolidine-2,4-dicarboxylate (t-2,4-PDC) on uptake and release of [3h]D
      aspartate in astrocytes and glutamatergic neurons.
AB  - Uptake and release processes in cerebellar astrocytes and granule neurons
      (glutamatergic) for glutamate were investigated by the use of [3H]D-aspartate, a
      non-metabolizable glutamate analog. The effects of DL-threo-beta
      benzyloxyaspartate (DL-TBOA) and L-trans-pyrrolidine-2,4-dicarboxylate (t-2,4
      PDC) on uptake and release of [3H]D-aspartate were studied. Both compounds
      inhibited potently uptake of [3H]D-aspartate in neurons and astrocytes (IC50
      values 10-100 microM), DL-TBOA being slightly more potent than t-2,4-PDC. Release
      of preloaded [3H]D-aspartate from neurons or astrocytes could be stimulated by
      addition of excess t-2,4-PDC whereas addition of DL-TBOA had no effect on [3H]D
      aspartate efflux. Moreover, DL-TBOA inhibited significantly the depolarization
      induced (55 mM KCI) release of preloaded [3H]D-aspartate in the neurons. The
      results reflect the fact that DL-TBOA is not transported by the glutamate
      carriers while t-2,4-PDC is a substrate which may heteroexchange with [3H]D
      aspartate. It is suggested that DL-TBOA may be used to selectively inhibit
      depolarization coupled glutamate release mediated by reversal of the carriers.

PMID- 11519724
TI  - Transcriptional regulation of the BCL-X gene by NF-kappaB is an element of
      hypoxic responses in the rat brain.
AB  - Signal transduction pathways that mediate neuronal commitment to apoptosis
      involve the nuclear factor kappa B (NF-kappaB) transcription factor. The bcl-x
      gene is a member of the bcl-2 family of genes that regulate apoptosis, and gives
      rise to two proteins, Bcl-XL and Bcl-XS, via alternative mRNA splicing. BCl-XL
      protein, like Bcl-2, is a dominant inhibitor of apoptotic cell death, whereas Bcl
      XS promotes apoptosis. While there is high expression of Bcl-XL in the developing
      and adult brain, few transcriptional control elements have been identified in the
      bcl-x promoter. There are two functional nuclear factor-kappa B (NF-kappaB) DNA
      binding sites clustered upstream of the brain-specific transcription start site
      in the upstream promoter region of murine bcl-x. Recombinant NF-kappaB proteins
      bind to these sites. Also NF-kappaB overexpression, coupled with bcl-x
      promoter/reporter assays using a series of murine bcl-x promoter and deletion
      mutants, has identified the downstream 1.1kb of the bcl-x promoter as necessary
      for basal promoter activity and induction by NF-kappaB in support of the
      hypothesis that NF-kappaB can act to enhance BCl-XL expression via highly
      selective interactions with the bcl-x promoter, where NF-kappaB binding and
      promoter activation are dependent on specific DNA binding site sequences and NF
      kappaB protein dimer composition. Hypoxia induces apoptosis in the hippocampus
      where the NF-kappaB dimers c-Rel/p50 and p50/pS0 bind to the bcl-x promoter NF
      kappaB site.

PMID- 11519727
TI  - Remyelination of the adult demyelinated mouse brain by grafted oligodendrocyte
      progenitors and the effect of B-104 cografts.
AB  - The 4e transgenic mouse is characterized by overexpression of the PLP gene.
      Heterozygous littermates containing three PLP gene copies develop and myelinate
      normally. However, a progressive CNS demyelination begins at 3-4 months of age.
      Despite focal demyelination, these animals survive for one year with hind limb
      paralysis. We used this CNS demyelination model to determine if grafts of CG4
      oligodendrocyte progenitors would survive and myelinate the adult CNS. Either CG4
      cells, or co-grafts of CG4/B 104 cells 11:1 ratio respectively) were performed.
      Grafted cells survived and migrated in the normal and transgenic brain. Non
      treated transgenic animals revealed extensive lack of myelin. Three months post
      transplant hosts with CG4 or co-transplants displayed a near normal myelin
      pattern. Double immunofluorescence for neurofilament and myelin basic protein
      revealed the presence of many naked axons in non-grafted transgenic animals.
      Those grafted with progenitor CG4 cells or cografts displayed a clear increase in
      remyelination. This data provides a new direction for the development of cell
      replacement therapies in demyelinating diseases.

PMID- 11519728
TI  - Characterization of human alpha4beta2 neuronal nicotinic receptors stably
      expressed in SH-EP1 cells.
AB  - These studies characterized human alpha4beta2 neuronal nicotinic receptors stably
      expressed in a human epithelial cell line (SH-EP1). Receptors in transfected SH
      EPI-halpha4beta2 cells were functional, as determined by increases in
      intracellular Ca2+ in response to a nicotine stimulus. Nicotine increased Fura-2
      fluorescence in a concentration-dependent manner with an apparent EC50 of 2.4
      microM, a response that was blocked by the specific antagonist mecamylamine. When
      cells were incubated in 50 nM nicotine for 24 hours, the Ca2+ response
      inactivated by 44%, an effect that recovered within 24 hours. SH-EP1-halpha4beta2
      cells expressed a single class of high affinity binding sites for [3H]cytisine
      with a Kd of 0.63 +/- 0.08 nM and a Bmax of 6,797 +/- 732 femtomoles/mg protein.
      Incubation of cells with 50 nM nicotine for 24 hours increased the Bmax by 45%
      without changing affinity, a concentration-dependent effect with an EC50, of 58.6
      nM. The nicotine-induced up regulation was reversible, and control values were
      achieved within 24 hours. Results indicate that SH-EPI-halpha4beta2 cells may be
      a good model system to study regulation of human alpha4beta2 receptors, the most
      abundant nicotinic receptor subtype in brain.

PMID- 11519729
TI  - Postmortem degradation of N-acetyl aspartate and N-acetyl aspartylglutamate: an
      HPLC analysis of different rat CNS regions.
AB  - N-acetyl aspartate (NAA), a putative marker of neuronal injury, can be measured
      non-invasively in patients by magnetic resonance spectroscopy (MRS).
      Interpretation of in vivo MRS data, however, requires neuropathological
      correlates to NAA alterations using autopsy or biopsy material. Since detailed
      hydrolysis data is lacking, NAA and the related dipeptide N-acetyl
      aspartylglutamate (NAAG) were quantified by high performance liquid
      chromatography (HPLC) in different rat CNS regions over 24 h postmortem. Both
      molecules decreased rapidly 1-4 h postmortem, and subsequently slower with time.
      The average reduction at 24 h was 46% and 38% for NAA and NAAG respectively. The
      NAA reduction was proportionally smaller in cortical areas (34-37%) compared to
      more caudal regions (54-58%). An exception was the optic nerve, a pure white
      matter tract, where NAA and NAAG hydrolysis was slower. The NAA/NAAG ratio
      remained relatively constant, but exhibited marked regional differences. The data
      show a significant postmortem degradation of NAA and NAAG that needs to be
      considered when these compounds are studied ex-vivo.

PMID- 11519730
TI  - Rapid functional analysis in Xenopus oocytes of Po protein adhesive interactions.
AB  - We have developed a coupled Xenopus oocyte expression system for evaluating the
      functional effects of mutations in known or suspected adhesion molecules, which
      allows for a very rapid assessment of intercellular adhesion. As a model protein,
      we first used Protein zero (Po), an adhesion molecule that mediates self-adhesion
      of the Schwann cell plasma membrane to form compact myelin in the mammalian PNS.
      A wide variety of mutations in Po cause certain human peripheral neuropathies,
      such as the Charcot-Marie-Tooth disease (CMT) type 1B and Dejerine-Sottas
      syndrome (DSS). After wild-type Po mRNA is injected, the protein is synthesized
      and correctly targeted to the oocyte cell surface. When two oocytes are paired,
      wild-type Po redistributes and concentrates at the cell-cell apposition region,
      and by electron microscopy, the oocyte pairs show close cell-cell appositions and
      are devoid of the microvilli that are observed in uninjected oocyte pairs. These
      are hallmark features of highly adhesive cell:cell interfaces. Several point
      mutations in Po were engineered, corresponding to the molecular defects in the
      CMT type 1B or DSS. The proteins encoded by these mutations reached the cell
      surface but failed to concentrate at the oocyte interface. Po carrying a point
      mutation that is found in DSS is not targeted on the plasma membrane and fail to
      accumulate at the cell-cell contact site.

PMID- 11519731
TI  - TCR peptide therapy in human autoimmune diseases.
AB  - Inflammatory Th1 cells reacting to tissue/myelin derived antigens likely
      contribute to the pathogenesis of diseases such as multiple sclerosis (MS),
      rheumatoid arthritis (RA), and psoriasis. One regulatory mechanism that may be
      useful for treating autoimmune diseases involves an innate second set of Th2
      cells specific for portions of the T cell receptor of clonally expanded
      pathogenic Th1 cells. These Th2 cells are programmed to respond to internally
      modified V region peptides from the T cell receptor (TCR) that are expressed on
      the Th1 cell surface in association with major histocompatibility molecules. Once
      the regulatory Th2 cells are specifically activated, they may inhibit
      inflammatory Th1 cells through a non-specific bystander mechanism. A variety of
      strategies have been used by us to identify candidate disease-associated TCR V
      genes present on pathogenic Th1 cells, including BV5S2, BV6S5, and BV13SI in MS,
      BV3, BV14, and BV17 in RA, and BV3 and BV13S1 in psoriasis. TCR peptides
      corresponding to the mid region of these BV genes were found to be consistently
      immunogenic in vivo when administered either i.d. in saline or i.m. in incomplete
      Freund's adjuvant (IFA). In MS patients, repeated injection of low doses of
      peptides (100-300 microg) significantly boosted the number of TCR-reactive Th2
      cells. These activated cells secreted cytokines, including IL-10, that are known
      to inhibit inflammatory Th1 cells. Cytokine release could also be induced in TCR
      reactive Th2 cells by direct cell-cell contact with Th1 cells expressing the
      target V gene. These findings indicate the potential of regulatory Th2 cells to
      inhibit not only the target Th1 cells, but also bystander Th1 cells expressing
      different V genes specific for other autoantigens. TCR peptide vaccines have been
      used in our studies to treat a total of 171 MS patients (6 trials), 484 RA
      patients (7 trials), and 177 psoriasis patients (2 trials). Based on this
      experience in 824 patients with autoimmune diseases, TCR peptide vaccination is
      safe and well tolerated, and can produce significant clinical improvement in a
      subset of patients that respond to immunization. TCR peptide vaccination
      represents a promising approach that is well-suited for treating complex
      autoimmune diseases.

PMID- 11519732
TI  - Mechanism of myelin breakdown in experimental demyelination: a putative role for
      calpain.
AB  - Although calpain has been extensively studied, its physiological function is
      poorly understood. In contrast, its role in the pathophysiology of various
      diseases has been implicated, including that of experimental allergic
      encephalomyelitis (EAE), an animal model of the demyelinating disease multiple
      sclerosis (MS). In EAE, calpain degrades myelin proteins, including myelin basic
      protein (MBP), suggesting a role for calpain in the breakdown of myelin in this
      disease. Subsequent studies revealed increased calpain activity and expression in
      the glial and inflammatory cells concomitant with loss of axon and myelin
      proteins. This suggested a crucial role for calpain in demyelinating diseases.

PMID- 11519734
TI  - Expression and function of the Drosophila ACT88F actin isoform is not restricted
      to the indirect flight muscles.
AB  - Most higher eukaryotic genomes contain multiple actin genes, yet the sequence
      differences between isoforms are few. In Drosophila melanogaster it was
      previously established that one of the six actin genes, Act88F, is expressed only
      in the indirect flight muscles (IFMs). These muscles are highly specialised for
      oscillatory contractions to power flight. The implication was that this isoform
      had tissue-specific properties. In this paper we show using two reporter
      constructs expressing either beta-galactosidase, Act88F-lacZ, or the green
      fluorescent protein, Act88F-GFP, that the Act88F promoter is active in a small
      number of other muscles, including leg (femoral) and uterine muscles. However,
      the levels of Act88F driven non-IFM expression are much less than in the IFMs. We
      have confirmed endogenous Act88F gene expression in these other muscles by in
      situ hybridisation studies. Using null and antimorphic mutants to show decreased
      walking ability and delayed/reduced oviposition we demonstrated that Act88F
      expression is functionally important in multiple muscle groups. Since the mutant
      effects are mild, this supports the expectation that other actin genes are also
      expressed in these muscles. The Act88F-GFP promoter-reporter also detects Act88F
      driven expression in the bristle-forming cells in the pupal wings. The
      implications of these results for the functions and developmental expression of
      the Drosophila ACT88F isoform are discussed.

PMID- 11519733
TI  - Mitochondrial involvement in brain function and dysfunction: relevance to aging,
      neurodegenerative disorders and longevity.
AB  - It is becoming increasingly evident that the mitochondrial genome may play a key
      role in neurodegenerative diseases. Mitochondrial dysfunction is characteristic
      of several neurodegenerative disorders, and evidence for mitochondria being a
      site of damage in neurodegenerative disorders is partially based on decreases in
      respiratory chain complex activities in Parkinson's disease, Alzheimer's disease,
      and Huntington's disease. Such defects in respiratory complex activities,
      possibly associated with oxidant/antioxidant balance perturbation, are thought to
      underlie defects in energy metabolism and induce cellular degeneration. Efficient
      functioning of maintenance and repair process seems to be crucial for both
      survival and physical quality of life. This is accomplished by a complex network
      of the so-called longevity assurance processes, which are composed of genes
      termed vitagenes. A promising approach for the identification of critical
      gerontogenic processes is represented by the hormesis-like positive effect of
      stress. In the present review, we discuss the role of energy thresholds in brain
      mitochondria and their implications in neurodegeneration. We then review the
      evidence for the role of oxidative stress in modulating the effects of
      mitochondrial DNA mutations on brain age-related disorders and also discuss new
      approaches for investigating the mechanisms of lifetime survival and longevity.

PMID- 11519735
TI  - Tetranectin in slow intra- and extrafusal chicken muscle fibers.
AB  - Tetranectin is a C-type lectin that occurs in the mammalian musculoskeletal
      system. In the present report we describe the first studies on an avian
      tetranectin. A full-length chicken tetranectin cDNA was isolated. Comparison of
      the deduced amino acid sequence of chicken tetranectin with mouse and human
      tetranectin showed an identity of 67 and 68%, respectively. Northern blot
      analysis demonstrated broad expression of chicken tetranectin mRNA, which was
      first detected on embryonic day 4. Tetranectin protein was detected in chicken
      serum and egg yolk. Since muscle is one of few tissues in which tetranectin
      protein is retained, we examined the distribution of tetranectin in various
      muscle types in chicken. Myofibers strongly positive for tetranectin were
      observed in several muscles including m. tibialis ant. and m. sartorius (from
      embryonic day 10 to adult). Using antibodies to fast and slow myosin heavy chains
      (MHC) and double immunostaining techniques, we found that tetranectin was
      restricted to slow (type I) muscle fibers. Similarly only slow intrafusal fibers
      accumulated tetranectin. The pattern of immunostaining in chickens differs
      markedly from that seen in mouse muscles, indicating that tetranectin performs a
      role in muscle that is not associated with a hitherto recognized muscle type or
      function.

PMID- 11519736
TI  - Comparative evolution of muscular dystrophy in diaphragm, gastrocnemius and
      masseter muscles from old male mdx mice.
AB  - X chromosome-linked muscular dystrophic mdx mouse lacks the sarcolemmal protein
      dystrophin and represents a genetic homologue of human Duchenne muscular
      dystrophy (DMD). The present study analysed some aspects of pathological
      processes such as fibrosis, frequency of centralized nuclei, presence of
      degenerative or regenerative fibres, expression of utrophin and associated
      protein complexes, and myosin heavy chain isoforms in three muscles [diaphragm
      (DIA), gastrocnemius (GTC) and masseter (MAS)] from old male mdx mice. All
      parameters investigated comparatively in these pathological muscles provided
      evidence that the MAS mdx muscle presents a slight deterioration pattern in
      comparison to that of DIA and GTC muscles. Utrophin and associated proteins are
      present in many cell clusters with continuous membrane labelling in MAS muscle.
      Respective proportions of myosin heavy chain isoforms, measured by
      electrophoresis/densitometry, showed only slight change in GTC muscle,
      significant evolution in DIA muscle but drastic isoform conversions in MAS
      muscle. These results highlighted the difference in deterioration susceptibility
      of various muscles to muscular dystrophy. The reason why this occurs in MAS
      muscles is still obscure and discussed in terms of the comparative developmental
      origins of these muscles.

PMID- 11519737
TI  - Response of mitochondrial function to hypothyroidism in normal and regenerated
      rat skeletal muscle.
AB  - Although thyroid hormones induce a well known decrease in muscle oxidative
      capacity, nothing is known concerning their effects on mitochondrial function and
      regulation in situ. Similarly, the influence of regeneration process is not
      completely understood. We investigated the effects of hypothyroidism on
      mitochondrial function in fast gastrocnemius (GS) and slow soleus (SOL) muscles
      either intact or having undergone a cycle of degeneration/regeneration (Rg SOL)
      following a local injection of myotoxin. Thyroid hormone deficiency was induced
      by thyroidectomy and propylthiouracyl via drinking water. Respiration was
      measured in muscle fibres permeabilised by saponin in order to assess the
      oxidative capacity of the muscles and the regulation of mitochondria in situ.
      Oxidative capacities were 8.9 in SOL, 8.5 in Rg SOL and 5.9 micromol O2/min/g dry
      weight in GS and decreased by 52, 42 and 39% respectively (P < 0.001) in
      hypothyroid rats. Moreover, the Km of mitochondrial respiration for the phosphate
      acceptor ADP exhibited a two-fold decrease in Rg SOL and intact SOL by
      hypothyroidism (P < 0.01), while mitochondrial creatine kinase activity and
      sensitivity of mitochondrial respiration to creatine were not altered. The
      results of this study demonstrate that hypothyroidism markedly altered the
      sensitivity of mitochondrial respiration to ADP but not to creatine in SOL
      muscles, suggesting that mitochondrial regulation could be partially controlled
      by thyroid hormones. On the other hand, mitochondrial function completely
      recovered following regeneration/degeneration, suggesting that thyroid hormones
      are not involved in the regeneration process per se.

PMID- 11519738
TI  - Calcium binding to an elastic portion of connectin/titin filaments.
AB  - Alpha-connectin/titin-1 exists as an elastic filament that links a thick filament
      with the Z-disk, keeping thick filaments centered within the sarcomere during
      force generation. We have shown that the connectin filament has an affinity for
      calcium ions and its binding site(s) is restricted to the beta-connectin/titin-2
      portion. We now report the localization and the characterization of calcium
      binding sites on beta-connectin. Purified beta-connectin was digested by trypsin
      into 1700- and 400-kDa fragments. which were then subjected to fluorescence
      calcium-binding assays. The 400-kDa fragment possesses calcium-binding activity;
      the binding constant was 1.0 x 10(7) M(-1) and the molar ratio of bound calcium
      ions to the 400-kDa fragment reached a maximum of 12 at a free calcium ion
      concentration of approximately 1.0 microM. Antibodies against the 400-kDa
      fragment formed a sharp dense stripe at the boundary of the A and the I bands,
      indicating that the calcium-binding domain constitutes the N-terminal region of
      beta-connectin, that is, the elastic portion of connectin filaments. Furthermore,
      we estimated the N-terminal location of beta-connectin of various origins (n =
      26). Myofibrils were treated with a solution containing 0.1 mM CaCl2 and 70
      microM leupeptin to split connectin filaments into beta-connectin and a
      subfragment, and chain weights of these polypeptides were estimated according to
      their mobility in 2% polyacrylamide slab gels. The subfragment exhibited a
      similar chain weight of 1200+/-33 kDa (mean+/-SD), while alpha- and beta
      connectins were variable in size according to their origin. These results suggest
      that the apparent length of the 1200-kDa subfragment portion is almost constant
      in all instances, about 0.34 microm at the slack condition, therefore that the C
      terminus of the 1200-kDa subfragment, that is, the N-terminus of the calcium
      binding domain, is at the N2 line region of parent filaments in situ. Because the
      secondary structure of the 400-kDa fragment was changed by the binding of calcium
      ions, connectin filaments could be expected to alter their elasticity during the
      contraction-relaxation cycle of skeletal muscle.

PMID- 11519740
TI  - The effects of ramp stretches on active contractions in intact mammalian fast and
      slow muscle fibres.
AB  - The effects of a ramp stretch (amplitude <6% muscle fibre length (L0), speed <
      13L0 s(-1)) on twitch tension and twitch tension re-development were examined in
      intact mammalian (rat) fast and slow muscle fibre bundles. The experiments were
      done in vitro at 20 degrees C and at an initial sarcomere length of 2.68 microm.
      In both fibre types, a stretch applied during the rising phase of the twitch
      response (including the time of stimulation) increased the re-developed twitch
      tension (15-35%). A stretch applied before the stimulus had little or no effect
      on the twitch myogram in fast muscle fibres, but it increased the twitch tension
      (approximately 5%) in slow muscle fibres. A similar stretch had little or no
      effect on tetanic tension in either muscle fibre type. In general, the results
      indicate that the contractile-activation mechanism may be stretch sensitive and
      this is particularly pronounced in slow muscle fibres. Recorded at a high
      sampling rate and examined at an appropriate time scale, the transitory tension
      response to a stretch rose in at least two phases; an initial rapid tension rise
      to a break (break point tension, P1a) followed by a slower tension rise (apparent
      P2a) to a peak reached at the end of the stretch. Plotted against stretch
      velocity, P1a tension increased in direct proportion to stretch velocity (viscous
      like) whereas, P2a tension (calculated as peak tension minus P1a tension)
      increased with stretch velocity to a plateau (visco-elastic). Examined at the
      peak of a twitch, P1a tension had a slope (viscosity coefficient) of 1.8 kN m(-2)
      per L0 s(-1) in fast fibres and 4.7 kN m(-2) per L0 s(-1) in slow muscle fibres.
      In the same preparations, P2a tension had a relaxation time of 8 ms in the fast
      muscle fibres and 25 ms in the slow muscle fibres. The amplitudes of both tension
      components scaled with the instantaneous twitch tension in qualitatively the same
      way as the instantaneous fibre stiffness. These fast/slow fibre type differences
      probably reflect differences in their cross-bridge kinetics.

PMID- 11519739
TI  - Regulation of nonmuscle myosins by heavy chain phosphorylation.
AB  - Functional activities of many nonmuscle myosin isoforms are (or are postulated to
      be) regulated by heavy chain phosphorylation. Depending on the myosin isoform,
      the serine or threonine residues located within the head (myosin I or myosin VI)
      or within the C-terminal tail domains (myosin II or myosin V) can be
      phosphorylated by more or less specific endogenous kinases. In some isoforms
      phosphorylation can occur both in the head and tail domains, as it has been found
      for myosin III. There are also isoforms that can be regulated both by the heavy
      and regulatory light chain phosphorylation, as for the example myosin II from
      slide mold Dictyostelium discoideum. The goal of this review was to describe
      recent findings on regulation of myosin I, myosin II, myosin III, myosin V and
      myosin VI isoforms by their heavy chain phosphorylation including the short
      charcteristics of the relevant kinases. The biological aspects of the
      phosphorylation are also discussed.

PMID- 11519741
TI  - The expression of dystrophin and alpha1-syntrophin during skeletal muscle
      regeneration.
AB  - The expression of dystrophin and alpha1-syntrophin in rat tibialis anterior
      muscles were evaluated during a cycle of regeneration after myonecrosis induced
      by the injection of cardiotoxin. Immunohistochemical studies were performed in
      cryosections of muscles on days 1, 3, 5, 7, 10, 14, 21 and 28 after injection of
      cardiotoxin. Western blot analysis was also examined in muscle on days 1, 3, 5,
      7, 10, 14, 21 and 28. In immunohistochemical studies, dystrophin was stained
      weakly at the sarcolemma of some regenerating muscle fibers on day 3, and by day
      10 it was stained strongly on almost all regenerating muscle fibers. Alpha1
      syntrophin was stained weakly at the sarcolemma of some regenerating fibers on
      day 5, and by day 14 it was detected on all regenerating muscle fibers. In
      Western blot analysis, dystrophin (DYS1) and alpha1-syntrophin (alpha1S) were
      completely absent on day 1. Re-expression of DYS1 and alpha1S was visible by day
      5 and accelerated thereafter. The Western blots of DYS1 and alpha1S were
      densitometrically analyzed on each day. The protein levels on each day were
      converted to the percentage of the protein level on day 28, which was taken as
      100%. From the sequential line based on these data, the following results were
      obtained on the chronological course of DYS1 and alpha1S. DYS1: 25% of the
      protein level on day 28 was reached by 3.5 days, 50% was reached by 5.3 days, and
      90% was reached by 6.9 days. Alpha1S: 25% of the protein level on day 28 was
      reached by 4.6 days, 50% was reached by 6.0 days, and 90% was reached by 12.5
      days. In this study, DYS1 regenerated earlier than alpha1S at the sarcolemma of
      regenerating muscle fibers.

PMID- 11519743
TI  - The Annual Meeting on Muscle Contraction and Cell Motility. Tokyo, Japan, 6-8
      January 2001.

PMID- 11519742
TI  - Microtubule disruption modulates the Rho-kinase pathway in vascular smooth
      muscle.
AB  - Microtubules constitute one of the main cytoskeletal components in eukaryotic
      cells. Recent studies have shown that microtubule disruption induced significant
      vasoconstriction or enhanced agonist-induced contraction in vascular smooth
      muscle. However, the underlying mechanisms are not clear. We hypothesize that
      microtubule disruption may affect contractile signaling in vascular smooth muscle
      and lead to the enhanced contraction. The present study demonstrates that both
      colchicine and nocodazole induced a small but sustained contraction (4-6% P0) in
      rat aortic rings. This microtubule disruption-induced contraction was abolished
      by co-treatment with either HA 1077 or Y-27632, both of which are relatively
      specific Rho-kinase inhibitors. However, co-treatment with ML-9, an inhibitor of
      myosin light chain kinase, (MLCK) did not have a significant effect on the
      colchicine-induced contraction. The enhanced KCl-induced contraction due to
      treatment with colchicine was also blocked by inhibition of Rho-kinase, but not
      by inhibition of MLCK. These results indicate that microtubule disruption
      modulates contractile signaling in vascular smooth muscle, mainly through the Rho
      kinase pathway, but not MLCK. Interestingly, the colchicine-enhanced,
      phenylephrine-induced contraction was not completely blocked by inhibition of Rho
      kinase suggesting that other signaling pathways might also be involved.

PMID- 11519744
TI  - Mapping the ligand binding site at protein side-chains in protein-ligand
      complexes through NOE difference spectroscopy.
AB  - This report describes a novel NMR approach for mapping the interaction surface
      between an unlabeled ligand and a 13C,15N-labeled protein. The method relies on
      the spin inversion properties of the dipolar relaxation pathways and records the
      differential relaxation of two spin modes, where ligand and protein 1H
      magnetizations are aligned either in a parallel or anti-parallel manner.
      Selective inversion of protein protons is achieved in a straightforward manner by
      exploiting the one-bond heteronuclear scalar couplings (1J(CH), 1J(NH)).
      Suppression of indirect relaxation pathways mediated by bulk water or rapidly
      exchanging protons is achieved by selective inversion of the water signal in the
      middle of the NOESY mixing period. The method does not require deuteration of the
      protein or well separated spectral regions for the protein and the ligand,
      respectively. Additionally, in contrast to previous methods, the new experiment
      identifies side-chain enzyme ligand interactions along the intermolecular binding
      interface. The method is demonstrated with an application to the B12-binding
      subunit of glutamate mutase from Clostridium tetanomorphum for which NMR chemical
      shift changes upon B12-nucleotide loop binding and a high-resolution solution
      structure are available.

PMID- 11519745
TI  - Methods for sequential resonance assignment in solid, uniformly 13C, 15N labelled
      peptides: quantification and application to antamanide.
AB  - The application of adiabatic polarization-transfer experiments to resonance
      assignment in solid, uniformly 13C-15N-labelled polypeptides is demonstrated for
      the cyclic decapeptide antamanide. A homonuclear correlation experiment employing
      the DREAM sequence for adiabatic dipolar transfer yields a complete assignment of
      the C(alpha) and aliphatic side-chain 13C resonances to amino acid types. The
      same information can be obtained from a TOBSY experiment using the recently
      introduced P9(12)1 TOBSY sequence, which employs the J couplings as a transfer
      mechanism. A comparison of the two methods is presented. Except for some aromatic
      phenylalanine resonances, a complete sequence-specific assignment of the 13C and
      15N resonances in antamanide is achieved by a series of selective or broadband
      adiabatic triple-resonance experiments. Heteronuclear transfer by adiabatic
      passage Hartmann-Hahn cross polarization is combined with adiabatic homonuclear
      transfer by the DREAM and rotational-resonance tickling sequences into two- and
      three-dimensional experiments. The performance of these experiments is evaluated
      quantitatively.

PMID- 11519746
TI  - A novel interactive tool for rigid-body modeling of multi-domain macromolecules
      using residual dipolar couplings.
AB  - Residual dipolar couplings (RDC), measured by dissolving proteins in dilute
      liquid crystal media, or by studying naturally paramagnetic molecules, have
      rapidly become established as routine measurements in the investigation of the
      structure of macromolecules by NMR. One of the most obvious applications of the
      previously inaccessible long-range angular information afforded by RDC is the
      accurate definition of domain orientation in multi-module macromolecules or
      complexes. In this paper we describe a novel program developed to allow the
      determination of alignment tensor parameters for individual or multiple domains
      in macromolecules from residual dipolar couplings and to facilitate their
      manipulation to construct low-resolution models of macromolecular structure. For
      multi-domain systems the program determines the relative orientation of
      individual structured domains, and provides graphical user-driven rigid-body
      modeling of the different modules relative to the common tensorial frame.
      Translational freedom in the common frame, and equivalent rotations about the
      diagonalized (x,y,z) axes are used to position the different modules in the
      common frame to find a model in best agreement with experimentally measured
      couplings alone or in combination with additional experimental or covalent
      information.

PMID- 11519747
TI  - Backbone dynamics of the natively unfolded pro-peptide of subtilisin by
      heteronuclear NMR relaxation studies.
AB  - The dynamics of the natively unfolded form of the pro-peptide of subtilisin (PPS)
      have been characterized at two different pHs (6.0 and 3.0) by 15N relaxation
      experiments. 15N relaxation data is obtained at multiple field strengths and a
      detailed comparison of spectral density mapping, the model free approach and the
      recently proposed Cole-Cole model free (CC-MF) analysis is presented. The CC-MF
      analysis provides a better fit to the observed magnetic field dependence of 15N
      relaxation data of unfolded PPS than conventional model free approaches and shows
      that fluctuations in R2 may be accounted for by a distribution of correlation
      times on the nanosecond timescale. A new parameter epsilon derives from the
      analysis and represents the width of the distribution function and the
      heterogeneity of the dynamics on the nanosecond timescale at a particular site.
      Particularly interesting is the observation that epsilon is sensitive to pH
      changes and that PPS samples a wider distribution of nanosecond time scale
      motions at less acidic pHs than at more acidic pHs. These results suggest that
      PPS experiences a higher degree of correlated motion at pH 6.0 and that
      electrostatic interactions may be important for inducing correlated motions on
      the nanosecond timescale in unfolded PPS.

PMID- 11519748
TI  - Efficient 13C/15N double labeling of the avirulence protein AVR4 in a methanol
      utilizing strain (Mut+) of Pichia pastoris.
AB  - Cost effective 13C/15N-isotope labeling of the avirulence protein AVR4 (10 kDa)
      of the fungal tomato pathogen Cladosporium fulvum was achieved with the
      methylotrophic yeast Pichia pastoris in a fermentor. The 13C/15N-labeled AVR4
      protein accumulated to 30 mg/L within 48 h in an initial fermentation volume of
      only 300 mL, while prolonged optimized overexpressions yielded 126 mg/L. These
      protein yields were 24-fold higher in a fermentor than in flask cultures. In
      order to achieve these protein expression levels, we used the methanol-utilizing
      strain (Mut+) of Pichia pastoris which has a high growth rate while growing on
      methanol as the only carbon source. In contrast, the methanol-sensitive strain
      (MutS) could intrinsically yield comparable protein expression levels, but at the
      expense of additional carbon sources. Although both strains are generally used
      for heterologous protein expression, we show that the costs for 13C-isotope
      labeling can be substantially reduced using the Mut+ strain compared to the MutS
      strain, as no 13C3-glycerol is required during the methanol-induction phase.
      Finally, nitrogen limitations were precluded for 15N-labeling by an optimal
      supply of 10 g/L (15NH4)2SO4 every 24 h.

PMID- 11519749
TI  - Dipolar filtered 1H-13C heteronuclear correlation spectroscopy for resonance
      assignment of proteins.
AB  - Resonance assignment is necessary for the comprehensive structure determination
      of insoluble proteins by solid-state NMR spectroscopy. While various 2D and 3D
      correlation techniques involving 13C and 15N spins have been developed for this
      purpose, H chemical shift has not been exploited sufficiently. We demonstrate the
      combination of the regular 1H-13C heteronuclear correlation (HETCOR) experiment
      and a dipolar filtered HETCOR technique to obtain better resolved 1H chemical
      shift spectra. The dipolar filtered experiment, MELODI-HETCOR. simplifies the 1H
      spectra by suppressing the directly bonded C-H correlation peaks and retaining
      only the medium- and long-range cross peaks. We apply this MELODI-HETCOR
      technique to several amino acids and proteins with various isotopic labeling
      patterns. The enhanced 1H chemical shift resolution allows the assignment of
      overlapping H alpha and H beta resonances in Ser, identifies the 1H chemical
      shift differences between neutral and cationic imidazole rings of His, and
      permits the assignment of residues with side chain nitrogen atoms in ubiquitin.
      The potential utility of this dipolar filtered HETCOR technique to resonance
      assignment of extensively labeled proteins is discussed.

PMID- 11519751
TI  - 1H, 13C and 15N resonance assignment of YajQ, a protein of unknown structure and
      function from Escherichia coli.

PMID- 11519750
TI  - The use of TROSY for detection and suppression of conformational exchange NMR
      line broadening in biological macromolecules.
AB  - The interference between conformational exchange-induced time-dependent
      variations of chemical shifts in a pair of scalar coupled 1H and 15N spins is
      used to construct novel TROSY-type NMR experiments to suppress NMR signal loss in
      [15N,1H]-correlation spectra of a 14-mer DNA duplex free in solution and
      complexed with the Antp homeodomain. An analysis of double- and zero-quantum
      relaxation rates of base 1H-15N moieties showed that for certain residues the
      contribution of conformational exchange-induced transverse relaxation might
      represent a dominant relaxation mechanism, which, in turn, can be effectively
      suppressed by TROSY. The use of the new TROSY method for exchange-induced
      transverse relaxation optimization is illustrated with two new experiments. 2D
      h1J(HN),h2J(NN) quantitative [15N,1H]-TROSY to measure h1J(HN) and h2J(NN) scalar
      coupling constants across hydrogen bonds in nucleic acids, and 2D (h2J(NN) +
      h1J(NH))-correlation-[15N,1H]-TROSY to correlate 1H(N) chemical shifts of bases
      with the chemical shifts of the tertiary 15N spins across hydrogen bonds using
      the sum of the trans-hydrogen bond coupling constants in nucleic acids.

PMID- 11519752
TI  - 1H and 15N sequential assignment and secondary structure of the monomeric N67D
      mutant of bovine seminal ribonuclease.

PMID- 11519753
TI  - Backbone resonance assignment of protease from Mason-Pfizer monkey virus.

PMID- 11519754
TI  - 1H, 15N, and 13C assignments and secondary structure identification for full
      length ribosomal protein L11 from Thermus thermophilus.

PMID- 11519755
TI  - 1H, 13C and 15N backbone assignments for the C-terminal globular domain of agrin.

PMID- 11519756
TI  - An ecologic study of childhood leukemia and population mixing in Ontario, Canada.
AB  - OBJECTIVE: To examine the association between population mixing and the incidence
      of childhood leukemia, specifically the acute lymphocytic leukemia (ALL) subtype
      among young children. METHODS: This ecologic study was based on incidence rates
      of leukemia in children aged 0-14 years. The Ontario Cancer Registry was used to
      identify the residence of 1394 leukemia cases between 1978 and 1992. Ecologic
      units were composed of census subdivisions in a 5-year period. Percent population
      change, determined from the Census of Canada, was employed as a measure of
      population mixing. The relationship between population mixing and childhood
      leukemia was examined separately after stratifying by the level of geographic
      isolation, defined according to urban-rural status. Analyses were also conducted
      separately in specific age groups and for the ALL subtype. RESULTS: Population
      growth in rural areas was associated with an increased incidence of leukemia,
      particularly for the ALL subtype in children aged 0-4 years (rate ratio = 1.8,
      95% confidence interval 1.1-2.8, for a greater than 20% population change
      relative to no increase in population). In contrast, an elevated risk due to
      population mixing was not observed in urban areas. CONCLUSIONS: Results from this
      study are consistent with results from similar studies conducted in the United
      Kingdom, which are suggestive of a role for an infectious agent in the etiology
      of childhood leukemia, as proposed in the Kinlen hypothesis.

PMID- 11519757
TI  - Grand multiparity and the risk of breast cancer: population-based study in
      Finland.
AB  - OBJECTIVES: The significance of reproductive factors on breast cancer risk has so
      far been characterized in populations with 5-paras as the highest category of
      parity. We extended these studies to a nationwide cohort of women with at least
      five births (grand multiparas = GM) by assessing the significance of parity, age
      at first birth, and average birth interval to the risk of breast cancer. METHODS:
      The study cohort obtained from the Population Register of Finland comprised
      86,978 GM-women; the incidence of cancer cases was obtained from the populated
      based Finnish Cancer Registry. During a follow-up of about 2 million person
      years, 1508 breast cancers were obtained. Standardized incidence ratios (SIRs)
      were calculated by dividing the number of observed cases by the number expected
      on the basis of national rates. RESULTS: In the GM cohort the incidence of breast
      cancer was low (SIR 0.55, 95% confidence interval 0.52-0.58). The relative risk
      decreased significantly from 5-paras (SIR 0.60, adjusted for the other study
      variables) to 8-paras (SIR 0.40). The increase in the age at first birth from
      less than 20 years to 30+ years nearly doubled the risk (SIR from 0.40 to 0.73).
      Parity was a significant risk determinant only in ductal cancer, while shortening
      the birth interval was protective only in lobular cancer. The incidence of
      advanced breast cancer among GM-women exceeded the population rate in
      premenopausal women and in women with first birth at the age of 30 years or more.
      CONCLUSIONS: Our study demonstrated that young age at first birth and increasing
      number of births were independent and powerful protective factors from the fifth
      child onwards, while birth interval was weak in this respect. The tumor
      morphology and the clinical advancement of malignancy modified the dependence of
      breast cancer risk on reproductive variables.

PMID- 11519758
TI  - A prospective study of green tea consumption and cancer incidence, Hiroshima and
      Nagasaki (Japan).
AB  - OBJECTIVES: Laboratory and animal studies have shown a protective effect of green
      tea on cancer of different sites, but epidemiological evidence is limited and
      inconclusive. This prospective study in Japan examined the association between
      green tea consumption and cancer incidence. METHODS: Subjects were 38,540 people
      (14,873 men, mean age 52.8 years; 23,667 women, mean age 56.8 years) who
      responded to a mail survey carried out between 1979 and 1981. A self-administered
      questionnaire ascertained consumption frequency of green tea using precoded
      answers (never, once per day, twice to four times per day, and five or more times
      per day). Follow-up continued until 31 December 1994. The study analyzed solid
      cancers (n = 3881); hematopoietic cancers (188); cancers of all sites combined
      (4069); and cancer of specific sites with more than 100 cases, i.e. stomach
      (901), colon (432), rectum (193), liver (418), gallbladder (122), pancreas (122),
      lung (436), breast (281), and bladder (122). Poisson regression was used to allow
      for city, gender, age, radiation exposure, smoking status, alcohol drinking, body
      mass index, education level, and calendar time. RESULTS: Green tea consumption
      was virtually unrelated to incidence of cancers under study. The relative risks
      of all cancers for those consuming green tea twice to four times per day and five
      or more times per day were 1.0 (95% confidence interval 0.91-1.1) and 0.98 (0.88
      1.1), respectively, as compared with those consuming green tea once per day or
      less. CONCLUSION: Our findings do not provide evidence that regular green tea
      consumption is related to reduced cancer risks.

PMID- 11519759
TI  - Agricultural use of organophosphate pesticides and the risk of non-Hodgkin's
      lymphoma among male farmers (United States).
AB  - OBJECTIVE: Data from three population-based case-control studies conducted in
      Kansas, Nebraska, Iowa, and Minnesota were pooled to evaluate the relationship
      between the use of organophosphate pesticides and non-Hodgkin's lymphoma (NHL)
      among white male farmers. METHODS: The data set included 748 cases of non
      Hodgkin's lymphoma and 2236 population-based controls. Telephone or in-person
      interviews were utilized to obtain information on the use of pesticides. Odds
      ratios (OR) adjusted for age, state of residence, and respondent status, as well
      as other pesticide use where appropriate, were estimated by logistic regression.
      RESULTS: Use of organophosphate pesticides was associated with a statistically
      significant 50% increased risk of NHL, but direct interviews showed a
      significantly lower risk (OR = 1.2) than proxy interviews (OR = 3.0). Among
      direct interviews the risk of small lymphocytic lymphoma increased with diazinon
      use (OR = 2.8), after adjustment for other pesticide exposures. CONCLUSIONS:
      Although we found associations between the risk of NHL and several groupings and
      specific organophosphate pesticides, larger risks from proxy respondents
      complicate interpretation. Associations, however, between reported use of
      diazinon and NHL, particularly diffuse and small lymphocytic lymphoma, among
      subjects providing direct interviews are not easily discounted.

PMID- 11519760
TI  - Attitudes to screening for cervical cancer: a population-based study in Sweden.
AB  - OBJECTIVES: To investigate how attitudes and beliefs about Pap smear screening
      affect women's choice to participate in organized or opportunistic screening.
      METHODS: Telephone interviews were conducted with 430 (69.0%) non-attenders and
      514 (80.7%) attenders to Pap smear screening, sampled from a population-based
      database. The interviews were conducted during 1998 in Uppsala County, Sweden.
      MAIN OUTCOME MEASURE: odds ratios (OR) and 95% confidence intervals (CI).
      RESULTS: Non-attendance was negatively associated with perceived severity of
      cervical cancer compared to other malignancies (OR = 1.9, 95% CI 1.1-3.4) as well
      as with satisfactory benefits (OR = 0.7, 95% CI 0.6-0.8), but positively
      associated with time-consuming and economical barriers (OR = 1.2, 95% CI 1.1-1.5
      and OR = 1.7, 95% CI 1.2-2.5, respectively). Non-attendance was also negatively
      associated with anxiety, but was of borderline significance (OR = 0.9, 95% CI 0.8
      1.0). The results were strengthened with increasing time since last smear or if
      self-reported attendance status was used instead of true attendance. Non
      attenders kept holding harder to their preferences than did attenders, stating
      they would not participate if their preferences were not met. CONCLUSIONS:
      Important differences in attitudes and beliefs exist between non-attenders and
      attenders in Pap smear screening. Rather than being emotional, the main barriers
      are either practical or rooted in misunderstandings and lack of relevant
      information. These insights offer opportunities to increase attendance rates
      considerably.

PMID- 11519761
TI  - Carotenoids, alpha-tocopherols, and retinol in plasma and breast cancer risk in
      northern Sweden.
AB  - OBJECTIVE: Using a nested case-referent design we evaluated the relationship
      between plasma levels of six carotenoids, alpha-tocopherol, and retinol, sampled
      before diagnosis, and later breast cancer risk. METHODS: In total, 201 cases and
      290 referents were selected from three population-based cohorts in northern
      Sweden, where all subjects donated blood samples at enrolment. All blood samples
      were stored at -80 degrees C. Cases and referents were matched for age, age of
      blood sample, and sampling centre. Breast cancer cases were identified through
      the regional and national cancer registries. RESULTS: Plasma concentrations of
      carotenoids were positively intercorrelated. In analysis of three cohorts as a
      group none of the carotenoids was found to be significantly related to the risk
      of developing breast cancer. Similarly, no significant associations between
      breast cancer risk and plasma levels of alpha-tocopherol or retinol were found.
      However, in postmenopausal women from a mammography cohort with a high number of
      prevalent cases, lycopene was significantly associated with a decreased risk of
      breast cancer. A significant trend of an inverse association between lutein and
      breast cancer risk was seen in premenopausal women from two combined population
      based cohorts with only incident cases. A non-significant reduced risk with
      higher plasma alpha-carotene was apparent throughout all the sub-analyses.
      CONCLUSION: In conclusion, no significant associations were found between plasma
      levels of carotenoids, alpha-tocopherol or retinol and breast cancer risk in
      analysis of three combined cohorts. However, results from stratified analysis by
      cohort membership and menopausal status suggest that lycopene and other plasma
      carotenoids may reduce the risk of developing breast cancer and that menopausal
      status has an impact on the mechanisms involved.

PMID- 11519762
TI  - Trends in lung cancer incidence in Sweden with special reference to period and
      birth cohorts.
AB  - OBJECTIVE: Sweden has one of the largest population-based cancer registers in the
      world that provides an opportunity to examine the trend of lung cancer incidence
      during a 35-year period. The primary aim of the present study was to estimate the
      effects of birth cohort, year of diagnosis (period), and age on the time trends
      of lung cancer incidence rates, and to analyze the gender-specific incidence of
      different histopathological types of lung cancer. RESULTS: Among men the age
      standardized incidence rate increased steadily up to 1982, when a peak of 49
      cases per 100,000 person-years was reached. Among women the incidence rate was
      lower and showed a monotonic increase throughout the observation period. The
      fastest rate of increase was noted among the youngest women. In women, but not in
      men, there was a steady increase in risk with each successive birth cohort. For
      both sexes there were large changes in the histopathological distributions of
      cases. The most notable was a major increase in adenocarcinomas. CONCLUSIONS: The
      overall age-adjusted incidence rate of lung cancer in Sweden has stabilized in
      men during the past two decades while rates are still increasing in women. In
      view of the continued high prevalence of smoking among young women, a future
      definite increase in the overall number of lung cancer cases in women can be
      expected.

PMID- 11519763
TI  - Cigar, pipe, and cigarette smoking and bladder cancer risk in European men.
AB  - OBJECTIVE: Estimating the risk of bladder cancer from cigar and pipe smoking is
      complicated by a small number of non-cigarette smokers included in most relevant
      studies. METHODS: We undertook a pooled analysis of the data on men from six
      published case-control studies from Denmark, France, Germany, and Spain, to
      assess the association between pipe and cigar smoking and bladder cancer, and to
      compare it with the risk from cigarette smoking. Complete history of tobacco
      smoking was ascertained separately for cigarettes, cigars, and pipe. Odds ratios
      (ORs) were estimated after adjusting for age, study, and employment in high-risk
      occupations. RESULTS: The pooled data set comprised 2279 cases and 5268 controls,
      of whom 88 cases and 253 controls smoked only cigars or pipe. The OR for pure
      cigarette smoking was 3.5 (95% confidence interval [CI] 2.9-4.2), that for pure
      pipe smoking was 1.9 (95% CI 1.2-3.1) and that for pure cigar smoking was 2.3
      (95% CI 1.6-3.5). The increase in the OR of bladder cancer that was observed with
      duration of smoking was non-significantly lower for cigars than for cigarettes.
      CONCLUSION: Our results suggest that smoking of cigars and pipe is carcinogenic
      to the urinary bladder, although the potency might be lower than for cigarettes.

PMID- 11519764
TI  - A prospective study on intake of animal products and risk of prostate cancer.
AB  - OBJECTIVE: Association between animal products and prostate cancer have been
      observed in numerous observational studies, but it is not clear whether the high
      fat content of these foods or some other component accounts for these
      associations. We examine these associations among 51,529 men who contributed
      detailed dietary data. METHODS: Participants of the Health Professionals Follow
      Up Study completed a semiquantitative food-frequency questionnaire in 1986, and
      subsequently in 1990 and 1994. Other data on potential risk factors were
      collected at baseline and in subsequent questionnaires during follow-up. Between
      1986 and 1996, 1897 total cases of prostate cancer (excluding stage A1) and 249
      metastatic cancers were identified. We used pooled logistic regression for
      analyses of diet and prostate cancer. RESULTS: Intakes of total meat, red meat,
      and dairy products were not associated with risk of total or advanced prostate
      cancer. An elevated risk for metastatic prostate cancer was observed with intake
      of red meat (relative risk (RR)= 1.6 for top vs. bottom quintile comparison, 95%
      confidence interval (CI) = 1.0-2.5); this association was slightly attenuated
      after controlling for saturated and alpha-linolenic fatty acids (RR = 1.5, 95% CI
      = 0.88-2.5). Processed meats, bacon and beef, pork or lamb as a main dish each
      contributed to an elevated risk of metastatic prostate cancer. Dairy product
      intake increased risk of metastatic prostate cancer (RR = 1.4, 95% CI = 0.91-2.2
      for top vs. bottom quintile comparison), but no association remained after
      controlling for calcium and other fatty acids. A high intake in both red meat and
      dairy product was associated with a statistically significant two-fold elevation
      in risk of metastatic prostate cancer, compared to low intake of both products;
      however, most of the excess risk could be explained by known nutritional
      components of these foods. CONCLUSIONS: Intakes of red meat and dairy products
      appear to be related to increased risk of metastatic prostate cancer. While known
      nutrients, such as calcium and fatty acids, may explain most of the dairy
      association observed, it appears that a portion of the risk of metastatic
      prostate cancer associated with red meat intake remains unexplained.

PMID- 11519765
TI  - Cutaneous malignant melanoma in Norway: variation by region of residence before
      and after the age 17.
AB  - OBJECTIVE: The aim of this study was to examine indirectly the importance of sun
      exposure during childhood and adolescence for the development of cutaneous
      malignant melanoma (CMM) by using a migration approach. METHODS: A nested case
      control study was carried out based on all inhabitants living in Norway at any
      time between 1960 and 1980. The cases were all diagnosed between 1960 and 1992 (n
      = 13,934) and 10 controls were added for each case (n = 130,507). Analyses were
      conducted on residence history in the southeast, mid-west and northern part of
      Norway, before and after age 17, also including working condition and educational
      level. RESULTS: Birthplace in southeast was found to be twice as hazardous for
      the risk of CMM compared with birthplace in the north. The region of residence
      before as well as after age 17 was shown to influence the risk of CMM; the risk
      pattern in migrants tended to change direction toward the risk in the region to
      which they move. Associations was found between indoor working condition and CMM,
      and between high level of education and CMM, which support the hypothesis that
      pattern of sun exposure in adulthood affects the risk of CMM. CONCLUSION: The
      results indicate sun exposure at any age to be of importance for the lifetime
      risk of CMM.

PMID- 11519766
TI  - Re: Diet and lung cancer mortality: a 1987 National Health Interview Survey
      cohort study.

PMID- 11519767
TI  - A double-blind, randomized comparison of intramuscularly and intravenously
      administered parecoxib sodium versus ketorolac and placebo in a post-oral surgery
      pain model.
AB  - BACKGROUND: Parecoxib sodium is an injectable cyclooxygenase-2-specific inhibitor
      developed for the treatment of acute pain. The analgesic efficacy of IV and IM
      parecoxib has been demonstrated in previous pilot studies using the post-oral
      surgery pain model. OBJECTIVE: This study was conducted to characterize the
      analgesic efficacy of parecoxib in healthy adults after oral surgery while
      comparing the efficacy and tolerability of the IV and IM routes of
      administration. METHODS: This was a double-blind, randomized, parallel-group,
      placebo- and active-controlled, single-dose, single-center trial. Patients
      experiencing moderate to severe post-operative pain after the extraction of > or
      =2 impacted third molars were randomized to receive parecoxib sodium 20 mg IM, 20
      mg IV, 40 mg IM, or 40 mg IV; ketorolac tromethamine 60 mg IM; or placebo.
      Patients assessed pain intensity and pain relief (PR) at baseline and at
      designated intervals for 24 hours after administration of study medication or
      until rescue medication was taken. Analgesic efficacy was assessed in terms of
      time-specific pain intensity difference (PID) and PR, time to onset of analgesia,
      and time to use of rescue medication. RESULTS: Three hundred four patients were
      randomized to treatment. Parecoxib sodium 20 and 40 mg IM or IV and ketorolac 60
      mg IM were significantly superior to placebo in PID, PR, time to onset of
      analgesia, and time to use of rescue medication (P < or = 0.05). Equal IV and IM
      doses of parecoxib were comparable on these measures; however, time to use of
      rescue medication was longer with IM compared with IV administration. Both doses
      of parecoxib were comparable to ketorolac 60 mg IM in time to onset of analgesia,
      but parecoxib 40 mg had a significantly longer duration of action (P < or =
      0.05). The few statistically significant differences in PID and PR between
      parecoxib 40 mg and ketorolac favored ketorolac versus parecoxib 40 mg IV at
      earlier time points and parecoxib 40 mg IM versus ketorolac at later time points
      (P < or = 0.05). All treatments were well tolerated. CONCLUSIONS: Parecoxib IV
      and IM provided effective analgesia. The 40-mg dose was comparable to ketorolac
      60 mg on most measures of analgesia but had a longer duration of action.

PMID- 11519768
TI  - Comparison of the clinical success and quality-of-life impact of brimonidine 0.2%
      and betaxolol 0.25 % suspension in patients with elevated intraocular pressure.
AB  - BACKGROUND: Brimonidine tartrate 0.2%, a selective alpha2-adrenergic receptor
      agonist, and betaxolol 0.25% suspension, a cardioselective beta1-adrenergic
      receptor antagonist, are used in the treatment of elevated intraocular pressure
      (IOP). OBJECTIVE: This study compared the clinical success and quality-of-life
      impact of 4 weeks of treatment with brimonidine 0.2% BID compared with those of 4
      weeks of treatment with betaxolol 0.25% suspension BID in patients with elevated
      IOP. METHODS: This was a multisite, double-masked, comparative clinical trial in
      patients with glaucoma or ocular hypertension. Patients were randomly assigned to
      receive either brimonidine or betaxolol BID. Morning IOP was measured at baseline
      and at weeks 1 and 4 using Goldmann applanation. Efficacy was determined by
      reduction in IOP from baseline. Patients experiencing a > or =20% reduction in
      IOP were considered to have a successful IOP-lowering response. The Glaucoma
      Disability Index questionnaire was administered at week 4 to assess quality-of
      life factors and the incidence of adverse events. Ophthalmic examinations were
      conducted at each visit. RESULTS: One hundred fifty-nine patients were randomized
      to treatment and completed the study, 81 receiving brimonidine and 78 receiving
      betaxolol. The majority were white (77.4%) and female (61.6%), and had a
      diagnosis of open-angle glaucoma (56.0%). After 4 weeks of treatment, both
      brimonidine and betaxolol effectively lowered IOP from baseline (mean IOP
      reductions: brimonidine, 5.96 mm Hg; betaxolol, 5.07 mm Hg; P = NS). However, a
      significantly higher percentage of brimonidine patients (52/81 [64.2%]) than
      betaxolol patients (37/78 [47.4%]) had a > or =20% reduction in IOP (P = 0.033).
      No serious adverse events were reported with either study medication. On the
      quality-of-life assessments, more betaxolol patients reported hyperemia (P =
      0.011), and the reported hyperemia was significantly more severe in betaxolol
      patients (P = 0.009). CONCLUSIONS: After 4 weeks of treatment, brimonidine 0.2%
      BID was clinically successful in significantly more patients and was better
      tolerated than 4 weeks of treatment with betaxolol 0.25% BID in this population.

PMID- 11519769
TI  - A placebo-controlled comparison of the effects on sexual functioning of bupropion
      sustained release and fluoxetine.
AB  - BACKGROUND: Many antidepressants are associated with sexual dysfunction, a side
      effect that may lead to patients' dissatisfaction and noncompliance with
      treatment. OBJECTIVE: This study compared the efficacy, tolerability, and effects
      on sexual functioning of bupropion sustained release (bupropion SR) and the
      selective serotonin reuptake inhibitor fluoxetine. METHODS: In this multicenter,
      randomized, double-blind, double-dummy, parallel-group study, patients with
      recurrent major depression were treated with bupropion SR 150 to 400 mg/d,
      fluoxetine 20 to 60 mg/d, or placebo for up to 8 weeks. Depression and sexual
      functioning status were assessed by site-specific trained investigators at weekly
      clinic visits; tolerability was assessed primarily by monitoring adverse events.
      RESULTS: Four hundred fifty-six patients participated in the study, 150 receiving
      bupropion SR, 154 fluoxetine, and 152 placebo. The majority of patients in each
      group completed the study (63% each, bupropion SR [n = 94] and fluoxetine [n =
      97]; 67%, placebo [n = 102]). Bupropion SR and fluoxetine were similarly
      effective in the treatment of depressive symptoms. Beginning at week 2 and
      continuing throughout the study, significantly more fluoxetine-treated patients
      experienced orgasm dysfunction than did patients receiving bupropion SR or
      placebo (P < 0.001); similar results were seen in patients defined as clinical
      responders (> or =50% decrease from baseline in 21-item Hamilton Rating Scale for
      Depression [HAM-D] total score) (P < 0.001) and in those experiencing remission
      of depression (HAM-D total score <8) (P < 0.05). At various time points, worsened
      sexual functioning, sexual desire disorder, sexual arousal disorder, and
      dissatisfaction with sexual functioning in those satistied at baseline were more
      frequently associated with fluoxetine treatment than with bupropion SR or
      placebo. Both active treatments were well tolerated. CONCLUSIONS: Bupropion SR
      and fluoxetine were similarly effective and well tolerated in the treatment of
      depression. Fluoxetine, however, was more frequently associated with sexual
      dysfunction compared with bupropion SR. Bupropion SR may be an appropriate
      initial choice for the treatment of depression in patients concerned about sexual
      functioning.

PMID- 11519770
TI  - Subgroup analysis versus post-hoc analysis.

PMID- 11519771
TI  - Economic evaluation of rofecoxib versus nonselective nonsteroidal anti
      inflammatory drugs for the treatment of osteoarthritis.
AB  - BACKGROUND: Results of phase III clinical trials of rofecoxib, a selective
      inhibitor of cyclooxygenase 2, have shown that osteoarthritis patients treated
      with rofecoxib had significantly fewer clinically significant gastrointestinal
      (GI) adverse events than those who received nonselective nonsteroidal anti
      inflammatory drugs (NSAIDs). OBJECTIVE: This paper explores the potential
      economic implications of the use of rofecoxib versus nonselective NSAIDs for the
      treatment of osteoarthritis via a decision analytic model based on rofecoxib
      clinical data and the published literature. METHODS: Base-case 1-year analyses
      were done with data on GI adverse events, specifically perforations, ulcers, and
      bleeds (PUBs), obtained from a prespecified pooled analysis of the rofecoxib
      clinical trials. Analyses were also performed using pooled results of two 12-week
      endoscopic surveillance trials, with adjustments for silent ulcers of 40% and
      85%. RESULTS: Under base-case conditions, the expected cost savings in GI
      problems and comedications averted with rofecoxib versus NSAIDs was 0.81 dollars
      per day, representing an 85% offset of the difference in drug price. For
      rofecoxib versus NSAIDs, the expected cost per PUB avoided with rofecoxib was
      4738 dollars, and expected cost per year of life saved was 18,614 dollars. In
      analyses based on endoscopic data, therapy with rofecoxib was less expensive than
      therapy with NSAIDs, regardless of silent ulcer adjustment. Results were most
      sensitive to prophylactic GI comedication rates, and were robust over a range of
      model assumptions and costs. CONCLUSIONS: In this analysis based on differences
      in clinically significant GI events for osteoarthritis patients, cost differences
      between rofecoxib and NSAIDs were markedly offset by expected cost savings in GI
      problems and comedications averted with rofecoxib. Costs per year of life saved
      with rofecoxib versus NSAIDs were well within accepted benchmarks for cost
      effectiveness. When endoscopic data alone were considered, rofecoxib was cost
      saving across all assumptions about silent ulcer rates.

PMID- 11519772
TI  - Psychometric evaluation of the 12-item short-form health survey (SF-12) in
      osteoarthritis and rheumatoid arthritis clinical trials.
AB  - BACKGROUND: The psychometric properties of the 12-Item Short-Form Health Survey
      (SF-12), a subset of the Medical Outcomes Study 36-Item Short-Form Health Survey
      (SF-36), have been tested in the general population and certain disease states.
      OBJECTIVE: The purpose of this study was to evaluate the psychometric properties
      of the SF-12 as a generic measure of health-related quality of life (HRQoL) in
      osteoarthritis (OA) and rheumatoid arthritis (RA) patient populations in clinical
      trials. METHODS: Data were aggregated from 5 clinical trials evaluating the
      efficacy of non-steroidal anti-inflammatory drugs in OA (n = 651) and RA (n =
      693) patients. Patient assessments in these trials were made using the SF-36 and
      commonly used clinical measures of OA and RA at baseline and after up to 6 weeks
      of treatment. For the items of the SF-36 contained in the SF-12, the item missing
      rate, computability of scores, floor and ceiling effects, factor structure, and
      item-component correlations were evaluated. Clinical variables and correlations
      of physical component summary (PCS-12) and mental component summary (MCS-12)
      scores of the SF-12 with the corresponding SF-36 component summary scores (PCS-36
      and MCS-36) were also examined. Analyses were conducted separately for OA and RA
      patients. RESULTS: A low individual SF-12 item missing rate (0.29% to 2.30%) and
      a high percentage score computability (90.9%-94.3%) were observed at baseline. No
      floor or ceiling effects at baseline were observed. The scree plot confirmed the
      2-factor structure of the SF-12 items. Items belonging to the physical component
      correlated more strongly with the PCS-12 than with the MCS-12; similarly, items
      belonging to the mental component correlated more strongly with the MCS-12 than
      with the PCS-12. The correlations between the PCS-12 and PCS-36 and between the
      MCS-12 and MCS-36 ranged from 0.92 to 0.96 (P < 0.001) at baseline and at week 2,
      4, or 6. Significant correlations ranging from -0.09 to -0.58 (P < 0.05) were
      observed between the SF-12 scores and clinical variables. CONCLUSION: The SF-12
      appears to be a psychometrically sound tool for the assessment of HRQoL in OA and
      RA patients.

PMID- 11519773
TI  - Quality of life and costs associated with micronized progesterone and
      medroxyprogesterone acetate in hormone replacement therapy for
      nonhysterectomized, postmenopausal women.
AB  - BACKGROUND: Because natural progesterone is poorly absorbed and rapidly
      metabolized, synthetic derivatives of progesterone, such as medroxyprogesterone
      acetate (MPA), are used in combination with estrogen in hormone replacement
      therapy. A micronized form of natural progesterone is available that is readily
      absorbed and reaches peak serum concentrations from 1 to 4 hours after
      administration. OBJECTIVE: The purpose of this study was to compare the quality
      of life (QOL), menopausal symptoms, and costs associated with a natural
      micronized progesterone (MP) formulation versus MPA as add-on therapy to estrogen
      in hormone replacement for post-menopausal women. METHODS: This prospective,
      multicenter, randomized, fixed-dose, open-label, parallel-group study enrolled
      postmenopausal, otherwise healthy, nonhysterectomized women 45 to 65 years of age
      who had been amenorrheic for > or =6 months and exhibited symptoms of estrogen
      deficiency. All women received 0.625 mg conjugated equine estrogens on days 1 to
      25 of a 30-day cycle; on days 12 to 25, women were randomized to receive either
      MP 200 mg or MPA 5 mg; patients were followed for 9 months. QOL, the primary end
      point, was measured at baseline and months 3, 6, and 9 using the 36-Item Short
      Form Health Survey (SF-36), the Nottingham Health Profile (NHP), and the
      condition-specific Women's Health Questionnaire (WHQ). Bleeding pattern,
      compliance, menopausal symptoms, and cost were evaluated as secondary end points.
      Costs (in 1997 Canadian dollars) were assessed from the societal perspective and
      included costs of study medication, hormone therapy monitoring, concomitant
      medication, outpatient resources, out-of-pocket expenses, and patient and
      caregiver time loss. RESULTS: A total of 182 women were enrolled; 89 received MP
      and 93 received MPA. Improvements in climacteric symptoms were observed from
      baseline to month 9 for both treatments. Mean scores on all domains of the SF-36
      at month 9 were greater than scores at baseline in both treatment groups but the
      increases were not statistically significant. All domains within the NHP and WHQ
      improved significantly over this period for both groups (P < or = 0.008). Only
      patients receiving MP showed specific improvements in the menstrual problems and
      cognitive domains of the WHQ. The difference in average 9-month cost per patient
      was not statistically significant, at Can 367 dollars +/- 120 dollars and Can 360
      dollars +/- 369 dollars for patients receiving MP and MPA, respectively.
      CONCLUSIONS: MP is a clinically effective, well-tolerated, and cost-comparable
      alternative to MPA.

PMID- 11519774
TI  - The relationship between introduction of American society of clinical oncology
      guidelines and the use of colony-stimulating factors in clinical practice in a
      Paris university hospital.
AB  - BACKGROUND: Clinical practice guidelines are issued periodically by professional
      medical societies or committees to assist practitioners in clinical decision
      making. However, it is unclear whether such guidelines have any lasting impact on
      clinical practice. OBJECTIVE: The purpose of this study was to assess the impact
      of the American Society of Clinical Oncology (ASCO) guidelines regarding use of
      hematopoietic colony-stimulating factors (CSF) on cancer care in a university
      hospital in Paris. METHODS: The study was performed at Hjpital Tenon, an 830-bed
      university hospital in Paris, in 1996 and 1997, both before and after the ASCO
      guidelines were implemented. The guidelines were first disseminated as a
      continuing medical education program and then actively implemented using a CSF
      prescription order form summarizing the guidelines. This form had to be used
      during the patient consultation and was sent to the Hjpital Tenon pharmacy for
      CSF dispensation. Even if CSF use did not comply with the ASCO guidelines, the
      pharmacy filled the prescription. Seven other university hospitals in Paris,
      where the ASCO guidelines were not actively implemented, comprised the control
      group. The main outcome measure was the proportion of prescriptions in compliance
      with the 1996 update of the ASCO guidelines. Secondary outcome measures were the
      proportions of prescriptions in compliance with ASCO guidelines regarding primary
      prophylactic, secondary prophylactic, and therapeutic CSF administration.
      RESULTS: Before implementation of the ASCO guidelines, CSF use in compliance with
      the guidelines was 39% (41/105) at the study site and 31% (16/51) at the control
      sites (P > 0.05). Six months after dissemination and implementation of the
      guidelines, the proportion of CSF prescriptions complying with ASCO guidelines
      increased significantly versus baseline (P = 0.003) in the study group, to 61%
      (50/82). However, even after the guidelines were implemented, compliance with
      guidelines on primary prophylactic CSF administration did not change
      significantly versus before implementation in the study group (12% [5/41] before
      implementation vs 6% [2/33] after implementation; P > 0.05). CONCLUSIONS: The
      results suggest an association between the active implementation strategy
      (continuing medical education and CSF prescription reminder form) and physician
      compliance with the ASCO guidelines. Implementation of the ASCO guidelines
      appears to have had some impact on medical practice.

PMID- 11519775
TI  - Tenecteplase: a review.
AB  - BACKGROUND: Certain shortcomings of the available thrombolytic agents have
      prompted the search for a more fibrin specific fibrinolytic agent with a longer
      half-life. Such properties would allow bolus administration, possibly leading to
      faster reperfusion of occluded arteries. OBJECTIVE: This article focuses on the
      new thrombolytic agent tenecteplase, reviewing its mechanism of action,
      pharmacokinetic characteristics, clinical efficacy, tolerability, and potential
      for drug interactions in the management of acute myocardial infarction. METHODS:
      English-language articles for inclusion in this review were identified through
      searches of MEDLINE, EMBASE, and International Pharmaceutical Abstracts from 1966
      to April 2001. The search terms used included tenecteplase, myocardial
      infarction, TNK, and TNK-tPA. Abstracts from recent conferences and symposia were
      also consulted. RESULTS: Tenecteplase is a variant of the native tissue-type
      plasminogen activator (tPA) molecule that has 14-fold greater fibrin specificity
      than alteplase, a longer half-life, slower plasma clearance, and 80-fold greater
      resistance to inhibition by plasminogen activator inhibitor type 1. Its half-life
      of approximately 18 minutes allows single-bolus administration. In comparative
      clinical trials, tenecteplase was found to have equivalent efficacy to
      recombinant tPA (alteplase). The rate of intracranial hemorrhage with
      tenecteplase was similar to that with alteplase, and tenecteplase was associated
      with fewer noncerebral complications and less need for blood transfusions.
      CONCLUSIONS: Tenecteplase appears to be as effective and well tolerated as
      alteplase in the management of acute myocardial infarction and offers the
      convenience of single-bolus administration.

PMID- 11519776
TI  - Healing and relapse rates in gastroesophageal reflux disease treated with the
      newer proton-pump inhibitors lansoprazole, rabeprazole, and pantoprazole compared
      with omeprazole, ranitidine, and placebo: evidence from randomized clinical
      trials.
AB  - BACKGROUND: The older proton pump inhibitor (PPI) omeprazole and the newer PPIs
      lansoprazole, rabeprazole, and pantoprazole are approved for the acute and
      maintenance treatment of gastroesophageal reflux disease (GERD). OBJECTIVE: On
      the basis of the results of randomized clinical trials, this study sought to
      estimate healing and relapse rates in acute and maintenance treatment of GERD
      with the newer PPIs compared with omeprazole, the histamine2-receptor antagonist
      ranitidine (the most frequent non-PPI comparator in studies of PPIs), and
      placebo. METHODS: A search of MEDLINE was conducted to identify randomized,
      controlled clinical trials that included a PPI in > or =1 treatment arm and
      assessed the healing of erosive esophagitis endoscopically. The primary outcome
      for studies of acute therapy was healing rate, and the primary outcome for
      studies of maintenance therapy was relapse rate. RESULTS: Fifty-three studies
      were identified, of which 38 involved acute therapy (12 excluded) and 15
      maintenance therapy. None of the studies of pantoprazole met the inclusion
      criteria for maintenance therapy. The 8-week overall healing rate ratios in the
      comparison of newer PPIs with omeprazole 20 mg/d were as follows: lansoprazole 30
      mg/d, 1.02 (95% CI, 0.98-1.06): rabeprazole 20 mg/d, 0.93 (95% CI, 0.87-1.00);
      and pantoprazole 40 mg/d, 0.98 (95% CI, 0.90-1.07). In the comparison of any PPI
      with ranitidine 300 mg/d, the ratios were as follows: lansoprazole, 1.62 (95% CI,
      1.46-1.76); rabeprazole, 1.36 (95% CI, 1.20-1.54); pantoprazole, 1.60 (95% CI,
      1.33-1.96); and omeprazole, 1.58 (95% CI, 1.41-1.78). Relapse rates over 1 year
      of treatment were similar between lansoprazole and rabeprazole. Compared with
      ranitidine, there were statistically significant differences in the rates of
      resolution of heartburn symptoms (P < 0.002), ulcer healing (P < 0.05), and
      relapse (P < 0.01). Similar results were seen in the comparison of PPIs with
      placebo in terms of rates of resolution of heartburn symptoms (P < 0.01), ulcer
      healing (P < 0.001), and relapse (P < 0.006). CONCLUSIONS: In this study, the
      newer PPIs were of similar efficacy to omeprazole in terms of heartburn control,
      healing rates, and relapse rates. All the PPIs were superior to ranitidine and
      placebo in healing erosive esophagitis and decreasing relapse rates.

PMID- 11519778
TI  - Preparation and blood compatibility of polysiloxane/liquid-crystal composite
      membranes.
AB  - Polysiloxane/liquid crystal composite membrane was first suggested to be used as
      biomaterials. In this work, the polydimethyl-methylhydrosiloxane and polydimethyl
      methylethylenesilosiane, as a substrate, were blended with cholesteryl oleyl
      carbonate (COC) in tetrahydrofuran, and then crosslinked into membranes on glass
      plates by means of the platinum catalyst at 110 degrees C for 20 min. The effects
      of the liquid-crystal content in composite membranes on the formation of liquid
      crystal phase were verified by the observation of optical polarization
      microscopy. The relationship between the morphology of the composite membranes
      and blood compatibility was identified by the dynamic blood-clotting tests,
      haemolysis ratio measurement, platelet adhesion and SEM observation. The results
      show that the blood-compatibility of composite membranes with the concentration
      of liquid crystal 20, 30% (wt) is more excellent than that of other composite
      membranes.

PMID- 11519777
TI  - Biomaterials and bone mechanotransduction.
AB  - Bone is an extremely complex tissue that provides many essential functions in the
      body. Bone tissue engineering holds great promise in providing strategies that
      will result in complete regeneration of bone and restoration of its function.
      Currently, such strategies include the transplantation of highly porous scaffolds
      seeded with cells. Prior to transplantation the seeded cells are cultured in
      vitro in order for the cells to proliferate, differentiate and generate
      extracellular matrix. Factors that can affect cellular function include the cell
      biomaterial interaction, as well as the biochemical and the mechanical
      environment. To optimize culture conditions, good understanding of these
      parameters is necessary. The new developments in bone biology, bone cell
      mechanotransduction, and cell-surface interactions are reviewed here to
      demonstrate that bone mechanotransduction is strongly influenced by the
      biomaterial properties.

PMID- 11519779
TI  - Phase purity of sol-gel-derived hydroxyapatite ceramic.
AB  - Calcium oxide was reported in the sol-gel-derived hydroxyapatite (HA) as an
      unavoidable major impurity. In this study phase purity of HA synthesized by sol
      gel route was explored using precursors of calcium nitrate tetrahydrate and
      triethyl phosphate. Two different drying methods, the fast drying of as-prepared
      precursors and the slow drying of aged precursors were adopted as major
      processing variables. The dried gels were subsequently calcined up to 600 degrees
      C. In the calcined powder from fast-dried gel, X-ray diffraction (XRD) patterns
      revealed an intense CaO peak. For the slow-dried gel, thermogravimetric analysis
      revealed a 2-step weight-loss behavior during heating. XRD analysis of the
      calcined powder, corresponding to the second weight-loss step, showed major peaks
      of hydroxyapatite and a very weak CaO peak. P-31 NMR analysis indicated formation
      of calcium phosphate complex during aging. Complete incorporation of Ca(NO3)2
      into the complex due to proper aging therefore diminishes CaO formation. It was
      also found that the minor CaO derived in the slow drying method can be easily and
      completely washed out just by distilled water.

PMID- 11519780
TI  - Electropolymerization of pyrrole on titanium substrates for the future
      development of new biocompatible surfaces.
AB  - Titanium and its alloys are widely used in load-bearing implants as a result of
      their excellent mechanical properties and corrosion resistance. In order to
      improve their performances with respect to osseointegration, the use of bioactive
      coatings has been suggested. Polypyrrole (PPy) has been chosen as coating polymer
      because of its ability to be electrochemically grown directly onto metallic
      substrates, of any shape and dimension, leading to remarkably adherent
      overlayers. This polymer, in addition to protecting the metal implant against
      corrosion, could be surface modified with biologically active molecules able to
      stimulate positive interactions with bone tissue. In this work, PPy
      electrosynthesis on both titanium and Ti-Al-V substrates has been investigated.
      The chemical composition and the morphology of the polymeric films, deposited
      under different conditions, were evaluated by X-ray photoelectron spectroscopy
      (XPS) and scanning electron microscopy (SEM), respectively.

PMID- 11519781
TI  - Material-dependent bone induction by calcium phosphate ceramics: a 2.5-year study
      in dog.
AB  - Bone induction by different calcium phosphate biomaterials has been reported
      previously. With regard to (1) whether the induced bone would disappear with time
      due to the absence of mechanical stresses and (2) whether this heterotopically
      formed bone would give rise to uncontrolled growth, a long-time investigation of
      porous hydroxyapatite ceramic (HA), porous biphasic calcium phosphate ceramic
      (TCP/HA, BCP), porous alpha-tricalcium phosphate ceramic (alpha-TCP) and porous
      beta-tricalcium phosphate ceramic (beta-TCP) was performed in dorsal muscles of
      dog, for 2.5 years. Histological observation, backscattered scanning electron
      microscopy observation and histomorphometric analysis were made on thin un
      decalcified sections of retrieved samples. Normal compact bone with bone marrow
      was found in all HA implants (n = 4) and in all BCP implants (n = 4), 48 +/- 4%
      pore area was filled with bone in HA implants and 41 +/- 2% in BCP implants. Bone
      like tissue, which was a mineralised bone matrix with osteocytes but lacked
      osteoblasts and bone marrow, was found in all beta-TCP implants (n = 4) and in
      one of the four alpha-TCP implants. Both normal bone and bone-like tissues were
      confined inside the pores of the implants. The results show that calcium
      phosphate ceramics are osteoinductive in muscles of dogs. Although the quality
      and quantity varied among different ceramics, the induced bone in both HA and BCP
      ceramics did neither disappear nor grow uncontrollably during the period as long
      as 2.5 years.

PMID- 11519782
TI  - Hydrogels for combination delivery of antineoplastic agents.
AB  - The systemic delivery of anticancer agents has been widely investigated during
      the past decade but localized delivery may offer a safer and more effective
      delivery approach. We have designed and synthesized a novel hydrogel to locally
      deliver antineoplastic agents, and demonstrate the different types of release
      that can be achieved from these hydrogels using three model drugs: methotrexate,
      doxorubicin, and mitoxantrone. Alginate was chemically modified into low
      molecular weight oligomers and cross-linked with a biodegradable spacer (adipic
      dihydrazide) to form biodegradable hydrogels. The model antineoplastic agents
      were loaded into the hydrogel via three different mechanisms. Methotrexate was
      incorporated within the pores of the hydrogel and was released by diffusion into
      the surrounding medium. Doxorubicin was covalently attached to the polymer
      backbone via a hydrolytically labile linker and was released following the
      chemical hydrolysis of the linker. Mitoxantrone was ionically complexed to the
      polymer and was released after the dissociation of this complex. These three
      release mechanisms could potentially be used to deliver a wide selection of
      antineoplastic agents, based on their chemical structure. This novel delivery
      system allows for the release of single or combinations of antineoplastic agents,
      and may find utility in localized antineoplastic agent delivery.

PMID- 11519783
TI  - Electrochemical characterization and immersion corrosion of a consolidated silver
      dental biomaterial.
AB  - A consolidated silver (CS) material, an alternative to dental amalgam, was
      studied for corrosion. Chemically precipitated silver particles were acid
      activated and pressure consolidated to a volume porosity of 25%. In selected
      tests comparisons were made between CS and melted and cast silver particles (MS),
      silver with a known mass fraction purity of 99.998% (FS), a silver-palladium
      alloy (SP). and a dispersed-phase amalgam (DA). Fusayama artificial saliva was
      used with controlled variations in pH, sulfide content, mucin content, and
      absorbed oxygen content. Electrochemical polarization, electrochemical impedance
      spectroscopy, and immersion methods were used. Results revealed differences in
      the zero current potentials E(I = 0) from forward polarization between CS and MS
      (or FS) in deaerated solution. By superposition of the cathodic polarization
      curves, the area for CS was increased by 7.3 times and was enclosed within an
      outer shell of material 5.5 microm thick. Polarization resistance was
      significantly the highest for SP, followed in order by MS (or FS) and CS or DA.
      With scanning electron microscopy, CS was shown to be significantly more
      susceptible than MS to long-term immersion corrosion. The modeled equivalent
      electrical circuits for CS and DA involved a double layer capacitance, a charge
      transfer resistance, and an element attributed to adsorption. The active pore
      depth for CS from the transmission line model for porous solids revealed
      satisfactory agreement with polarization results. It is concluded that the
      corrosion susceptibility of CS in Fusayama solution, while similar to that for
      DA, is greater than it is for MS.

PMID- 11519784
TI  - Influence of betacyclodextrin on the release of poorly soluble drugs from inert
      and hydrophilic heterogeneous polymeric matrices.
AB  - The release behavior of poorly soluble drugs (naproxen and ketoprofen) from inert
      (acrylic resins) and hydrophilic swellable (high-viscosity
      hydroxypropylmethylcellulose) tableted matrices containing betacyclodextrin
      (betaCD) was investigated. The results demonstrated that, in both cases, betaCD
      can enhance the rate of drug release. Matrices obtained from formulations in
      which lactose replaced betaCD were also evaluated. BetaCD in inert matrices
      causes a dramatic increase in the rate of drug release, higher than that promoted
      by lactose which merely acts as a channelling agent. This result suggests that
      possible in situ formation of the drug-betaCD complex. which causes an
      improvement in apparent drug solubility, could have a greater influence on the
      rate of drug release than the possible increase of water uptake by a soluble
      filler. Indeed, if the opposite were true, lactose would be more effective in
      increasing the rate of drug release than betaCD, because of its greater
      solubility in water. On the contrary, in the case of hydrophilic matrices,
      lactose proves to be much more effective in promoting drug release than betaCD.
      It seems that, while the bulky interaction compound can freely diffuse through
      water-filled pores of inert systems, its diffusion through swollen macromolecular
      chains of hydrophilic matrices may be hindered. This hypothesis was supported by
      data obtained from binary (drug/polymer) and ternary (drug/polymer/betaCD)
      hydrophilic matrices using a betaCD-containing dissolution media.

PMID- 11519785
TI  - In vivo degradation of 14C-labeled small intestinal submucosa (SIS) when used for
      urinary bladder repair.
AB  - The rate of in vivo degradation was determined for a naturally occurring
      biomaterial derived from the extracellular matrix of the small intestinal
      submucosa (SIS). The SIS was labeled by giving weekly intravenous injections of
      10 microCi of 14C-proline to piglets from 3 weeks of age until the time of
      sacrifice at 26 weeks. The resultant SIS prepared from these pigs contained
      approximately 10(3) fold more 14C than unlabeled tissues. The labeled SIS was
      used to repair experimental defects in the urinary bladder of 10 dogs. The
      animals were sacrificed at post-operative times ranging from 3 days to 1 year and
      the remodeled urinary bladder tissue was harvested for evaluation of 14C by a
      combination of liquid scintillation counting and accelerator mass spectrometry.
      The remodeled tissue contained less than 10% of the 14C (disintegrations per
      minute/gram tissue wet weight) at 3 months post-surgery compared to the SIS
      biomaterial that was originally implanted. The SIS scaffold was replaced by host
      tissue that resembled normal bladder both in structure and function. After
      implantation, 14C was detected in highest concentrations in the blood and the
      urine. The SIS bioscaffold provides a temporary scaffold for tissue remodeling
      with rapid host tissue remodeling, degradation, and elimination via the urine
      when used as a urinary bladder repair device.

PMID- 11519786
TI  - Creating porous tubes by centrifugal forces for soft tissue application.
AB  - Chemically crosslinked poly(2-hydroxyethyl methacrylate) (PHEMA) tubes were
      synthesized by applying centrifugal forces to propagating polymer chains in
      solution. Initiated monomer solutions, with a composition typical for PHEMA
      sponges, were placed into a cylindrical mold that was rotated about its long
      axis. As polymerization proceeded, phase separated PHEMA formed a sediment at the
      periphery under centrifugal action. The solvent remained in the center of the
      mold while the PHEMA phase gelled, resulting in a tube. By controlling the
      rotational speed and the formulation chemistry (i.e., monomer, initiator and
      crosslinking agent concentrations), the tube dimensions and wall morphology were
      manipulated. Tube manufacture was limited by a critical casting concentration
      [M]c, above which only rods formed. All tubes had an outer diameter of 2.4 mm,
      reflecting the internal diameter of the mold and a wall thickness of
      approximately 40-400 microm. Wall morphologies varied from interconnecting
      polymer and water phases to a closed cell, gel-like, structure. Concentric tubes
      were successfully prepared by using formulations that enhanced phase separation
      over gelation/network formation. This was achieved by using formulations with
      lower concentrations of monomer and crosslinking agent and higher concentrations
      of initiator. This technique offers a new approach to the synthesis of polymeric
      tubes for use in soft tissue applications, such as nerve guidance channels.

PMID- 11519787
TI  - Platelet interactions with titanium: modulation of platelet activity by surface
      topography.
AB  - Endosseous implants initially come into contact with blood. Thus, the nature of
      the interactions between blood and implanted endosseous implants may influence
      subsequent bone healing events in the peri-implant healing compartment. We
      conducted studies to address the following question: Does implant surface
      microtexture modulate platelet activity? We used commercially pure Ti (cpTi)
      disks with four different surface finishes: dual acid-etched (DAE), 320 grit
      (320G) abraded, machined, and p1200 polished cpTi. Surfaces were characterized by
      scanning electron microscopy (SEM) and optical profilometry. The DAE and 320G
      surfaces presented more complex microtextures than the machined or polished
      surfaces. Platelet activities were measured by quantifying platelet adherence,
      platelet-derived microparticle (MP) formation, and P-selectin expression as
      function of surface type. Platelet adhesion, measured using a lactate
      dehydrogenase (LDH) assay. was increased on DAE and 320G surfaces compared to
      machined and polished surfaces (p < 0.05). M P formation and P-selectin
      expression, assayed by flow cytometry, also showed increased activation of
      platelets on DAE and 320G surfaces. Because increased activation of platelets may
      lead to up-regulation of osteogenic responses during bone healing, these results
      may explain the enhanced osteoconductivity known to occur with DAE cpTi surfaces
      in comparison with machined cpTi surfaces.

PMID- 11519788
TI  - Bisphosphonate derivatized polyurethanes resist calcification.
AB  - Calcification of polyurethane cardiovascular implants is an important disease
      process that has the potential to compromise the long-term function of devices
      such as polymer heart valves and ventricular assist systems. In this study we
      report the successful formulation and characterization of bisphosphonate
      derivatized polyurethanes, hypothesized to resist implant calcification based on
      the pharmacologic activity of the immobilized bisphosphonate. Fully polymerized
      polyurethanes (a polyurea-polyurethane and a polycarbonate polyurethane) were
      modified (post-polymerization) with bromoalkylation of the hard segments followed
      by attachment of a bisphosphonate group at the bromine site. These bisphosphonate
      polyurethanes resisted calcification in rat 60 day subdermal implants compared to
      nonmodified control polyurethane implants, that calcify. Bisphosphonates-modified
      polyurethanes were also studied in circulatory implants using a pulmonary valve
      cusp replacement model in sheep. Polyurethane cusps modified with bisphosphonate
      did not calcify in 90 day implants. compared to control polyurethane cusps
      implants, that demonstrated nodular surface oriented calcific deposits. It is
      concluded that bisphosphonate modified polyurethanes resist calcification both in
      subdermal implants and in the circulation. This novel biomaterial approach offers
      great promise for long-term blood stream implantation with calcification
      resistance.

PMID- 11519789
TI  - Ring-opening polymerization of lactones in the presence of hydroxyapatite.
AB  - The ring-opening polymerization of epsilon-caprolactone, delta-valerolactone (VL)
      and D,L-lactide, respectively, in the presence of different proportions of
      hydroxyapatite (HA) was catalyzed by stannous (II)octoate (SnOct2) at 130 degrees
      C and resulted in composites. The lactones were almost completely converted to
      the polymers within a reaction time of 70 up to 240 min. The number-average
      molecular weights Mn as determined by size exclusion chromatography decreased
      with increasing content of HA. The initiating efficiency of HA as calculated from
      the difference of the polymerization degrees P. obtained with and without HA
      turned out to be relatively low with ca. 11 to 0.5% for 1 to 80 wt% HA,
      respectively. For the polymerization of VL, the initiating efficiency of HA was
      on the average threefold higher. The quantitative proof of non-extractable
      polymer on HA by means of thermogravimetric analysis, fourier transform infrared
      spectroscopy with photoacoustic detection and differential scanning calorimetry
      confirmed the initiating efficiency of HA as mentioned above. This poly(lactone)
      can be debound from HA by treatment with aqueous HCl. Hence it is assumed to be
      ionically bound.

PMID- 11519790
TI  - Acute effects of prostaglandin D2 to induce airflow obstruction and airway
      microvascular leakage in guinea pigs: role of thromboxane A2 receptors.
AB  - BACKGROUND: Although prostaglandin D2 (PGD2), a mast cell-derived inflammatory
      mediator, may trigger allergic airway inflammation, its potency and the mechanism
      by which it induces airway microvascular leakage, a component of airway
      inflammation, is not clear. OBJECTIVE: We wanted to evaluate the relative potency
      of PGD2 to cause microvascular leakage as compared to airflow obstruction,
      because both responses were shown to occur simultaneously in allergic airway
      diseases such as asthma. The role of thromboxane A2 receptors (TP receptors) in
      inducing these airway responses was also examined. METHODS: Anesthetized and
      mechanically ventilated guinea pigs were given i.v. Evans blue dye (EB dye) and,
      1 min later, PGD2 (30, 100, 300 or 1,000 nmol/kg). For comparison, the effect of
      150 nmol/kg histamine or 2 nmol/kg leukotriene D4 (LTD4) was also examined. Lung
      resistance (R(L)) was measured for 6 min (or 25 min for selected animals) and the
      lungs were removed to calculate the amount of extravasated EB dye into the
      airways as a marker of leakage. In some of the animals, specific TP receptor
      antagonists, S-1452 (10 microg/kg) or ONO-3708 (10 mg/kg), or a thromboxane A2
      synthase inhibitor, OKY-046 (30 mg/kg), was pretreated before giving PGD2.
      RESULTS: Injection of PGD2 produced an immediate and dose-dependent increase in
      RL (peaking within 1 min), which was significant at all doses studied. At 1,000
      nmol/kg, PGD2 induced a later increase in R(L), starting at 3 min and reaching a
      second peak at 8 min. By contrast, only PGD2 at doses of 300 and 1,000 nmol/kg
      produced a significant increase in EB dye extravasation. The relative potency of
      1,000 nmol/kg PGD2 to induce leakage as compared to airflow obstruction was
      comparable to histamine at most of airway levels, but less than LTD4. Both
      responses caused by PGD2 were completely abolished by S-1452 and ONO-3708, but
      not by OKY-046. CONCLUSION: PGD2 may induce airway microvascular leakage by
      directly stimulating TP receptors without generating TXA2 in guinea pigs.
      Microvascular leakage may play a role in the development of allergic airway
      inflammation caused by PGD2.

PMID- 11519791
TI  - Expression of prostaglandin H synthase-1 and -2 in murine intrauterine and
      gestational tissues from mid pregnancy until term.
AB  - These studies were undertaken to evaluate the changes in mRNA expression of
      prostaglandin H synthase (PGHS)-1 and -2 in murine gestational tissues during the
      latter half of pregnancy. Gestational tissues (decidual caps, membranes
      surrounding the fetus, and placentae), uterus, and cervix were collected from
      pregnant mice at days 12, 14, 16, 18, and 19 (am and pm) of gestation (n = 4),
      and total RNA was isolated and evaluated for PGHS-1 and PGHS-2 expression by
      northern blot analysis. Expression was normalized to GAPDH. There were no
      significant increases in PGHS-2 mRNA expression in any of the tissues studied
      through gestation. In contrast, expression of PGHS-1 mRNA increased significantly
      at term in the uterus and fetal membranes. In the placenta, mRNA for PGHS-1 was
      elevated at day 18 and remained elevated over the remainder of the study. These
      findings suggest that, in the mouse, increased production of PGs by uterine and
      intrauterine tissues during pregnancy is associated with up-regulation of PGHS-1
      and not PGHS-2.

PMID- 11519792
TI  - Changes in prostaglandin E2 (PGE2) levels in paw exudate, stomach and kidney of
      arthritic rats: effects of flosulide.
AB  - To further examine the organ-specific toxic effects of selective and non
      selective COX-2 inhibitors in adjuvant arthritis (CAA), we assessed the PGE2
      concentration in various organs. AA was induced by intradermal injection of
      Mycobacterium butyricum. Fourteen days after inoculation, AA rats were selected
      and treated orally every day for two weeks with the selective COX-2 inhibitor,
      flosulide, or the COX-1-COX-2 inhibitor, indomethacin. The time-course of paw
      swelling was determined. At the end of treatments, PGE2 was extracted from paw,
      stomach (wall and mucosa) and kidney and its concentration was determined by
      ELISA. Paw edema increase was accompanied by a rise in PGE2 concentration. PGE2
      also increased in stomach (mucosa and wall) and kidney. The anti-inflammatory
      treatment with flosulide (5 mg/kg x day), and indomethacin (1 mg/kg x day),
      reduced plantar edema by 98.0% and 74.4% respectively. Both drugs greatly
      decreased PGE2 levels in paw (73.7-53.2%), stomach wall (84.5-80.3%), stomach
      mucosa (109.9-110.9%) and kidney (92.9-97.5% respectively). However, PGE2
      reductions in AA rats did not fall significantly below control values.

PMID- 11519793
TI  - Implication of gastrin in cyclooxygenase-2 expression in Helicobacter pylori
      infected gastric ulceration.
AB  - Gastroduodenal ulcerations have worldwide distribution and the infection with
      Helicobacter pylori (HP) has been implicated in pathogenesis of this disease. The
      HP infection is usually accompanied by hypergastrinemia and enhanced generation
      of prostaglandins (PG), both implicated in the pathogenesis of peptic ulcerations
      but no study has been undertaken to assess the relationship between the HP
      infection and coexpression of gastrin and cyclooxygenases (COX), the rate
      limiting enzymes in the PG production. Since HP infection, usually accompanying
      peptic ulcerations, results in increased release of gastrin, a potent gastric
      mitogen that might be capable to induce COX-2 and to generate PG, we decided 1)
      to compare the seroprevalence of HP and its cytotoxic protein, CagA, in gastric
      ulcer patients with those in age- and gender-matched controls; 2) to determine
      the gene expression of gastrin and its receptors (CCK(B)-R) at the margin of
      gastric ulcer and in the mucosa of antrum and corpus before and after successful
      eradication of HP, 3) to assess the plasma levels and gastric luminal contents of
      gastrin before and after HP eradication and 4) to examine the mRNA and enzyme
      protein expression of COX-1 and COX-2 as well as the PGE2 generation in ulcer
      margin tissue and gastric antral and fundic mucosa before and after the HP
      eradication. The trial material included 20 patients with gastric ulcer and 40
      age- and gender-matched controls. Anti-HP and anti-CagA IgG seroprevalence was
      estimated by specific antisera using ELISA tests. Gene expressions of gastrin,
      CCK(B)-R, COX-1 and COX-2 were examined using RT-PCR with beta-actin as a
      reference and employing Western blotting for COX-2 expression, while gastrin and
      PGE2 were measured by RIA. All gastric ulcers were located at smaller curvature
      within the antral mucosal area. The seroprevalence of HP, especially that
      expressing CagA, was significantly higher in gastric ulcers (85%) than in
      controls (62.5%). Both gastrin and CCK(B)-R mRNA were detected by RT-PCR in ulcer
      margin and gastrin mRNA was overexpressed in remaining antral mucosa, while
      CCK(B)-R mRNA was overexpressed in fundic mucosa of HP infected patients.
      Similarly, COX-2 mRNA and protein were found in margin of gastric ulcer and in
      the HP infected antral and fundic mucosa but not in the mucosa of HP eradicated
      patients in whom ulcers completely healed and gastrin was expressed only in
      antrum, CCK(B)-R only in corpus, while COX-1 was detected both in antrum and
      corpus. HP positive gastric ulcer patients showed about three times higher levels
      of plasma immunoreactive gastrin and about 50% higher luminal gastrin contents
      than the HP negative controls and this increased plasma and luminal gastrin was
      normalized following the HP eradication. A significant fall in gastrin and CCK(B)
      R mRNA expression was noticed six weeks after HP eradication in gastric antral
      and fundic mucosa, while COX-2 mRNA completely disappeared after this treatment.
      We conclude that 1) HP infected gastric ulcer margin coexpresses gastrin, its
      receptors (CCK(B)-R), and COX-2; 2) HP infection may be implicated in gastric
      ulceration via increased release of gastrin that could be responsible for the
      overexpression of COX-2 that in turn could help ulcer healing through the
      stimulation of mucosal cell growth, restoration of the glandular structure and
      angiogenesis in the ulcer area and 3) gastrin produced in HP infected antral
      mucosa seems to be involved in the induction of COX-2 and PG production by this
      enzyme and this may contribute to the ulcer healing.

PMID- 11519795
TI  - Comparative modeling of breakthrough curves of bovine serum albumin in anion
      exchange chromatography.
AB  - The experimental results of a previous study of the mass transfer kinetics of
      bovine serum albumin (BSA) in ion-exchange chromatography, under nonlinear
      conditions, were reevaluated using the general rate model of chromatography.
      Solutions of this model were obtained numerically. The influences of axial
      dispersion, the resistance to mass transfer from the bulk mobile phase to the
      surface of the packing particles, and the intraparticle mass transfer resistances
      on the profiles of the breakthrough curves of BSA were investigated. The results
      obtained are compared to those of a previous investigation of the same data,
      using the simple transport-dispersive model and the lumped pore diffusion model.
      The results obtained show that the use of an oversimplified model for the
      analysis of chromatographic data can lead to erroneous interpretations of the
      experimental data and to misunderstandings of the fundamentals of the processes
      involved. Finally, a theoretical comparison between the properties and the range
      of application of the three models is provided.

PMID- 11519794
TI  - Effect of arachidonic acid on duodenal enterocyte ATPases.
AB  - Duodenal ion transport processes are supported by ATPase enzymes in basolateral
      membranes of the enterocyte. In vivo studies have shown that long term n-6 poly
      unsaturated fatty acid (PUFA) supplementation in rats causes increases in
      intestinal Ca absorption, coupled with a higher total calcium balance and bone
      calcium content. The present in vitro study was undertaken to test the effect of
      arachidonic acid (AA), a highly unsaturated (and thus physiologically potent)
      member of the n-6 PUFA family, on ATPases in enterocyte basolateral membranes
      isolated with a sorbitol density gradient procedure. This paper presents results
      which show that AA inhibits Na+,K+-ATPase in a dose-dependent manner (-67% of
      basal activity at a concentration of 30 microg/ml, P < 0.005) but that this
      effect is not mediated by protein kinase C, as shown by the use of the protein
      kinase C blocker calphostin (0.5 microM). Indomethacin (IDM) at 0.1 mM, a cyclo
      oxygenase blocker, could also not reverse the inhibitory effect of AA on Na+,K+
      ATPase. Ca2+-ATPase, on the other hand, is not affected significantly (-10%, P >
      0.05) by arachidonic acid at 30 microg/ml.

PMID- 11519796
TI  - Preparative isolation and purification of six diterpenoids from the Chinese
      medicinal plant Salvia miltiorrhiza by high-speed counter-current chromatography.
AB  - A high-speed counter-current chromatography (HSCCC) method was developed for the
      preparative separation and purification of six diterpenoids. dihydrotanshinone I,
      cryptotanshinone, methylenetanshiquinone, tanshinone I, tanshinone IIA and
      danshenxinkun B from the Chinese medicinal plant Salvia miltiorrhiza Bunge. The
      crude diterpenoids were obtained by extraction with ethanol-n-hexane (1:1, v/v)
      from S. miltiorrhiza Bunge. Preparative HSCCC with the two-phase solvent systems
      A composed of n-hexane-ethanol-water (10:5.5:4.5, v/v) and B composed of n-hexane
      ethanol-water (10:7:3, v/v) was successfully performed in a stepwise elution
      yielding six relatively pure diterpenoids from 300 mg of the crude extract in a
      single run. The purities of dihydrotanshinone I, cryptotanshinone,
      methylenetanshiquinone, tanshinone I, tanshinone IIA and danshenxinkun B were
      88.1, 98.8, 97.6, 93.5, 96.8 and 94.3%, respectively.

PMID- 11519797
TI  - Separation of mistletoe lectins based on the degree of glycosylation using
      boronate affinity chromatography.
AB  - A mixture of two mistletoe lectins (MLs) has been separated according to the
      degree of glycosylation using boronate affinity chromatography. The mistletoe
      lectins, mistletoe lectin I (MLI) and mistletoe lectin III (MLIII) with degrees
      of glycosylation of 6.1 and 3.8%, respectively, were used in the investigation.
      MLI exhibited a higher retention time than MLIII due to its higher degree of
      glycosylation. Separation was confirmed by sodium dodecyl sulfate-polyacrylamide
      gel electrophoresis. The developed method may lead to new applications for the
      boronate affinity technique, as well as provide an alternative separation method
      for MLs.

PMID- 11519798
TI  - Automated mass analysis of low-molecular-mass bacterial proteome by liquid
      chromatography-electrospray ionization mass spectrometry.
AB  - Due to the presence of a large number of proteins in cell extracts, ion
      chromatograms of cell extracts obtained by electrospray ionization mass
      spectrometry (ESI-MS) can be quite complicated. It is found that the elevated
      baseline in an ion chromatogram contains many protein signals. One deficiency of
      current commercially available LC-ESI-MS data interpretation software is found to
      be the lack of functional operation that allows automated mass spectral
      integration and interpretation over signals hidden in the baseline. This current
      limitation can be overcome by a technique that involves the introduction of
      artificial pulses to an ion chromatogram by removing the solvent mixer in the
      HPLC pump. These artificial pulses are treated as chromatographic peaks by the
      software, thereby allowing automated spectral integration over the duration of a
      pulse. The reliability of mass analysis from the integrated spectra is shown to
      be dependent on spectral interpretation parameters such as mass spectral baseline
      threshold. The application of this method is demonstrated for rapid detection and
      mass analysis of low-molecular-mass proteins from cell extracts of Escherichia
      coli or Bacillus globigii.

PMID- 11519799
TI  - Preparative isolation and purification of astaxanthin from the microalga
      Chlorococcum sp. by high-speed counter-current chromatography.
AB  - High-speed counter-current chromatography was applied to the isolation and
      purification of astaxanthin from microalgae. The crude astaxanthin was obtained
      by extraction with organic solvents after the astaxanthin esters were saponified.
      Preparative high-speed counter-current chromatography with a two-phase solvent
      system composed of n-hexane-ethyl acetate-ethanol-water (5:5:6.5:3, v/v) was
      successfully performed yielding astaxanthin at 97% purity from 250 mg of the
      crude extract in a one-step separation.

PMID- 11519800
TI  - Application of coil centrifugal counter-current chromatography to the separation
      of macrolide antibiotic analogues III. Effects of flow-rate, mass load and
      rotation speed on the peak resolution.
AB  - As the third part of our methodology studies on the application of centrifugal
      counter-current chromatography to the preparative separation of macrolide
      antibiotic analogues, we have investigated the effects of various parameters on
      the retention of stationary phase and peak resolution. Our results show that the
      retention percentage of the stationary phase has linear relationships with both
      flow-rate at 1 to 3 ml/min and rotation speed at 100 to 700 rpm, but their
      correlation coefficients are negative (-1.000) and positive (0.9821),
      respectively. The peak resolution (Rs) is inversely proportional to the flow-rate
      (Fr) and mass load (Ml), but directly proportional to the rotation speed (Rrev).
      Their correlation coefficients in linear regression for the preparative
      separation in laboratory scale are -0.981 to -1.000 for Rs=a+bFr at flow-rates of
      1 to 3 ml/min, -0.929 to -0.993 for Rs=a+bMl at mass loads of 12.5 to 100 mg, and
      0.975 to 0.998 for Rs=a+bRrev at rotation speeds of 300 to 700 rpm, respectively.
      Preparative separation of six very closely related macrolide antibiotics, which
      belong to ascomycin and rapamycin analogues, has also been successfully achieved
      under optimized conditions.

PMID- 11519801
TI  - Robotic automated clean-up for detection of fumonisins B1 and B2 in corn and corn
      based feed by high-performance liquid chromatography.
AB  - A high-performance liquid chromatography (HPLC) system with fluorescence
      detection and an automated on-line solid-phase extraction procedure for
      fumonisins B1 and B2 in corn and corn-based products is described. Different
      amounts of strong anion-exchange, C18 and end-capped C18 (C(18 ec)) silicas were
      tested for sample clean-up. Various HPLC parameters were analyzed. The best
      methodology was found to be extraction with acetonitrile-water and clean up on
      C(18 ec) disposable extraction cartridges. The system has the advantage of
      running in an unattended mode of operation and allows processing of 40 samples
      without system refuel, performing clean-up, o-phthaldialdehyde derivatization,
      injection and fumonisin detection by fluorescence detection linked to a computer
      integrator for automated data processing. Recoveries were performed with corn and
      corn-based feed samples (n=3) spiked with 0.1, 0.5, 1.0, 5.0 and 10 microg/g.
      Average recoveries for corn and corn-based feed were, respectively, 92.6 and
      88.3% with relative standard deviations (RSDs) of 5.04 and 6.22%, for fumonisin
      B1 and 91.2 and 89.0% with RSDs of 5.84 and 7.88% for fumonisin B2. Detection
      limits (S/N=3) for corn and corn-based feed were approximately 0.03 microg/g for
      fumonisin B1 and 0.05 microg/g for fumonisin B2

PMID- 11519802
TI  - Flow field-flow fractionation of poly(ethylene oxide): effect of carrier ionic
      strength and composition.
AB  - The effects of carrier ionic strength and electrolyte composition on the
      retention of poly(ethylene oxide) in aqueous flow field-flow fractionation have
      been investigated in this work. The study shows retention to be particularly
      sensitive to the presence of salts, as well as to the nature of the cation.
      Specifically, retention effects due to sample load are found to be very different
      in solutions containing potassium salts compared to those observed in solutions
      of the corresponding sodium salts. In a potassium-containing medium, the
      dependence of retention on sample mass is similar to that found previously for
      polyelectrolytes. This effect, which is particularly prominent for samples of low
      molecular mass, can be attributed to specific interactions between cation and
      polymer.

PMID- 11519803
TI  - Retention behaviour of amylopectins in asymmetrical flow field-flow fractionation
      studied by multi-angle light scattering detection.
AB  - Asymmetrical flow field-flow fractionation (FFF) with multi-angle light
      scattering (MALS) detection was applied for the fractionation of amylopectins
      from four different sources. Samples originated from genetically modified
      potatoes and waxy maize. Amylopectins were dissolved in a 1 mol l(-1) sodium
      hydroxide solution or water. With an injected mass of 0.2 microg, well below
      overloading conditions, a decrease of the apparent hydrodynamic radius with
      increasing inlet flow-rate was observed. Moreover, a decrease of the radius of
      gyration with increasing elution volume was recorded by the MALS detector.
      Steric/hyperlayer effects are a feasible explanation for this behaviour. The
      observed radius of gyration at the steric inversion point was in the order of 0.3
      microm, which is smaller than the theoretically calculated inversion point.
      Apparently, the amylopectin behave as macromolecules with a larger hydrodynamic
      radius than expected on basis of their radius of gyration and are subjected to
      significant lift forces. The results were confirmed by four fractionations with
      varying flow-rates but constant ratio of cross to outlet-flow. In contrast to the
      normal mode operation, the retention of the amylopectins depended strongly on the
      applied flow-rates and was close to that of a much smaller 10 kDa dextran.
      Apparent molar masses in the order of between 10(7) and 10(9) g mol(-1) were
      obtained. The results are contrasted with enzymatically degraded and oxidised
      starch samples that were fractionated in the normal mode.

PMID- 11519804
TI  - Optimization and application of high-resolution gas chromatography with ion trap
      tandem mass spectrometry to the determination of polychlorinated biphenyls in
      atmospheric aerosols.
AB  - Optimization of the Finnigan GCQ ion trap mass spectrometry (ITMS) system and a
      clean-up procedure were carried out in order to apply high-resolution gas
      chromatography-tandem mass spectrometry for the analysis of polychlorinated
      biphenyls (PCBs) in aerosols. Six ITMS operating parameters, including isolation
      time, excitation voltage, excitation time, "q" value, ion source temperature and
      electron energy were adjusted in order to optimize the instrument analytical
      performance. The adjustment of all parameters substantially increased the
      sensitivity of ITMS in the MS-MS mode. Changes in isolation time did not
      particularly affect ITMS sensitivity while ion source temperature had the
      strongest influence. After optimization, a limit of detection of 600 fg/microl
      with S/N varying from 8 up to 91 was achieved. The application of the optimized
      ITMS parameters conjointly with the developed clean-up procedure resulted in
      method detection limits of 10-20 fg/m3 for the determination of PCBs, in the
      particulate and gas phase of the atmospheric aerosol of background areas in the
      Eastern Mediterranean and Sweden.

PMID- 11519805
TI  - Fitting adsorption isotherms to the distribution data determined using packed
      micro-columns for high-performance liquid chromatography.
AB  - Knowing the adsorption isotherms of the components of a mixture on the
      chromatographic system used to separate them is necessary for a better
      understanding of the separation process and for the optimization of the
      production rate and costs in preparative high-performance liquid chromatography
      (HPLC). Currently, adsorption isotherms are usually measured by frontal analysis,
      using conventional analytical columns. Unfortunately, this approach requires
      relatively large quantities of pure compounds, and hence is expensive, especially
      in the case of pure enantiomers. In this work, we investigated the possible use
      of packed micro-bore and capillary HPLC columns for the determination of
      adsorption isotherms of benzophenone, o-cresol and phenol in reversed-phase
      systems and of the enantiomers of mandelic acid on a Teicoplanin chiral
      stationary phase. We found a reasonable agreement between the isotherm
      coefficients of the model compounds determined on micro-columns and on
      conventional analytical columns packed with the same material. Both frontal
      analysis and perturbation techniques could be used for this determination. The
      consumption of pure compounds needed to determine the isotherms decreases
      proportionally to the second power of the decrease in the column inner diameter,
      i.e. 10 times for a micro-bore column (1 mm I.D.) and 100 times for capillary
      columns (0.32 mm I.D.) with respect to 3.3 mm I.D. conventional columns.

PMID- 11519806
TI  - On-line clean-up of pressurized liquid extracts for the determination of
      polychlorinated biphenyls in feedingstuffs and food matrices using gas
      chromatography-mass spectrometry.
AB  - This paper describes a fast and simple pressurized liquid extraction method for
      the determination of polychlorinated biphenyls (PCBs) in feedingstuffs and food
      matrices. The method is based on a simultaneous extraction/clean-up step
      requiring a minimum of sample handling. The final analysis was performed with gas
      chromatography-mass spectrometry. Seven PCBs (28, 52, 101, 118, 138, 153 and 180)
      were analyzed, all of which are indicator congeners that, according to European
      legislation should be included in the analytical monitoring program. The
      extracted matrices were spiked feed for poultry and two certified reference
      materials naturally contaminated with PCBs (cod-liver oil and milk powder), which
      showed excellent conformity with certified data.

PMID- 11519807
TI  - Fast clean-up for polychlorinated dibenzo-p-dioxins, dibenzofurans and coplanar
      polychlorinated biphenyls analysis of high-fat-content biological samples.
AB  - A fast clean-up procedure for the low level analysis of polychlorinated dibenzo-p
      dioxins. polychlorinated dibenzofurans and coplanar polychlorinated biphenyls in
      highly fatty biological matrices using high capacity disposable multi-layer
      silica columns is presented. Results were compared with gel permeation
      chromatography for removal of lipids. Analytical criteria such as recovery rates,
      repeatability, reproducibility and robustness are evaluated through a broad range
      of biological matrices and reference materials analysis. The final proposed
      procedure for the complete analysis, including pressurized liquid extraction,
      Power-Prep system clean-up and GC-high-resolution MS analysis requires only 48 h,
      and allows the simultaneous preparation of up to 10 samples.

PMID- 11519809
TI  - Retrospective identification of chemical warfare agents by high-temperature
      automatic thermal desorption-gas chromatography-mass spectrometry.
AB  - An automated thermal desorption (ATD)-gas chromatography-mass spectrometry method
      was developed for the analysis of selected chemical warfare (CW) agents. Suitable
      methods were developed for analytes of high volatility to low volatility. The
      less volatile CW agents required the purchase and installation of a high
      temperature valve upgrade kit allowing valve temperatures of up to 260 degrees C
      to be reached. The limit of detection was 50 ng on the tube for most CW agents in
      full scan. Chloropicrin exhibited some temperature dependence, with detection
      limits improving as ATD temperatures were decreased below 150 degrees C. A sample
      storage trial was undertaken to establish the most suitable storage environment
      for CW agents adsorbed onto Tenax TA. Temperature and time of storage were found
      to influence recovery of analytes with best recoveries being observed after 1 day
      storage in a freezer (-12 degrees C). This method was evaluated during a trial of
      procedures for sampling and identification of chemical agents at Porton Down, UK.
      Sulfur mustard was detected downwind of a simulated exploded munition.

PMID- 11519808
TI  - Optimized thiol derivatizing reagent for the mass spectral analysis of
      disubstituted epoxy fatty acids.
AB  - A novel procedure is described for the derivatization of fatty acid epoxides in
      the presence of their corresponding diols. The acidic character of 2,3,5,6
      tetrafluorobenzenethiol promotes favorable mass fragmentation of linoleate and
      arachidonate derived epoxide derivatives and reduces alkene isomerization to a
      manageable side reaction, eliminated through the addition of a thiol scavenger.
      After silylation, regioisomeric mixtures of epoxy- and dihydroxylipids are
      simultaneously detected and discriminated using gas chromatography with electron
      impact mass spectral detection. Silylated hydroxysulfanyloctadecanoids yielded
      instrumental detection limits of 5 pg/microl, sufficient sensitivity for the
      quantification of endogenous epoxylipids.

PMID- 11519810
TI  - Reversed-phase electrochromatography of amino acids and peptides using porous
      polymer monoliths.
AB  - Efficient and rapid separation of minute levels of amino acids and bioactive
      peptides is of significant importance in the emerging field of proteomics as well
      as in the clinical and pharmaceutical arena. We have developed novel UV-initiated
      acrylate-based porous polymer monoliths as stationary phases for capillary- and
      chip-electrochromatography of cationic, anionic, and neutral amino acids and
      peptides, followed by absorbance or laser-induced fluorescence detection. The
      rigid monoliths are cast-to-shape and are tunable for charge and hydrophobicity.
      For separations at low pH, monoliths containing quaternary amine moieties were
      used to achieve high electroosmotic flow, and for high pH separations monoliths
      with acidic sulfonic acid groups were employed. Efficient and reproducible
      separations of phenylthiohydantoin-labeled amino acids, native peptides, and
      amino acids and peptides labeled with naphthalene-2,3-dicarboxaldehyde (NDA) were
      achieved using both negatively- and positively-charged polymer monoliths in
      capillaries. Separation efficiencies in the range of 65,000-371,000 plates/m were
      obtained with capillary electrochromatography. Buffer composition and the degree
      of column hydrophobicity were studied systematically to optimize separations. The
      monoliths were also cast in the microchannels of glass chips and
      electrochromatographic separation followed by laser-induced fluorescence
      detection of three NDA-labeled bioactive peptides was obtained.

PMID- 11519811
TI  - Capillary electrochromatography in anion-exchange and normal-phase mode using
      monolithic stationary phases.
AB  - Hydrophilic macroporous weak and strong anion-exchange stationary phases have
      been prepared in a monolithic format within untreated fused-silica capillaries by
      the simple thermally or UV-initiated polymerization of 2-dimethylaminoethyl
      methacrylate, 2-hydroxyethyl methacrylate and ethylene dimethacrylate in the
      presence of a binary porogenic mixture of dodecanol and cyclohexanol. The
      tertiary amino functionalities were then alkylated in situ to afford strong anion
      exchangers. These new monolithic stationary phases with optimized porous
      properties were used for the CEC separation of various organic anions. Thus, a
      mixture of 2-substituted propionic acid drugs (profens) was separated in 13 min
      and high column efficiencies of up to 231,000 plates/m were achieved. The
      separation of substituted benzoic acids indicates that the selectivity results
      primarily from the anion-exchange interactions, while electrophoretic migration
      contributes only slightly. In addition, these hydrophilic anion-exchangers are
      also able to separate weakly acidic, neutral and basic compounds such as phenols,
      xanthines and aromatic amines in normal-phase electrochromatographic mode.

PMID- 11519812
TI  - Chiral separation of six diastereomeric flavanone-7-O-glycosides by capillary
      electrophoresis and analysis of lemon juice.
AB  - The diastereomers of six major flavanone-7-O-glycosides (naringin, prunin,
      narirutin, hesperidin, neohesperidin and eriocitrin) were completely separated
      for the first time by chiral capillary electrophoresis (CE) employing various
      buffers and chiral selectors on the basis of the results achieved in 1998 in our
      research group by Mellenthin. The following chiral additives to the background
      electrolyte (BGE) were examined: native cyclodextrins (CDs; alpha-, beta- and
      gamma-CD), neutral cyclodextrin derivatives (dimethyl-beta-CD, hydroxypropyl-beta
      CD, hydroxypropyl-gamma-CD) and charged cyclodextrin derivatives (carboxymethyl
      beta-CD, carboxyethyl-beta-CD). The effect of CD type, CD concentration and pH
      value on chiral recognition will be discussed in the following article. In this
      work, lemon juice (Citrus limon L.) was also examined by chiral CE. Eriocitrin
      and hesperidin could be identified as characteristic flavanones and chiral
      separation of their diastereomers could be achieved according to the developed
      chiral method by capillary electrophoresis using a 0.2 M borate buffer at pH 10.0
      and with 5 mM gamma-CD as chiral selector.

PMID- 11519813
TI  - Pulsed amperometric detection of calystegines separated by capillary
      electrophoresis.
AB  - Calystegines are polyhydroxyalkaloids with a nortropane skeleton. They are
      oxidized by pulsed amperometry at a gold electrode due to their vicinal hydroxyl
      groups similar to monosaccharides, but at a slightly higher potential. Compared
      to carbohydrates, calystegines exhibit lower acidity, thus the effective
      electrophoretic mobility as anions in 0.1 M NaOH is lower, independent of their
      molecular mass. The acidity and mobility of calystegines increase with the number
      of hydroxyl groups. The influence of temperature and power dissipation in the
      capillary and changes of the inner surface on the migration times was eliminated
      by cooling and subtraction of the electroosmotic flow velocity. The high
      resolving power of capillary zone electrophoresis allows the separation of
      calystegines with the same number of hydroxyl groups. Detection is linear from 2
      to 200 mg L(-1) with a 1 nL injection volume. Calystegines were determined in
      crude plant sap after filtration without further sample purification.

PMID- 11519814
TI  - Recovery of 4-nonylphenol and 4-nonylphenol ethoxylates from river sediments by
      pressurised liquid extraction.
AB  - The pressurised liquid extraction (PLE) of 4-nonylphenol (4-NP) with methanol
      (100 degrees C and 100 atm) from river sediments was compared with methanolic
      Soxhlet extraction, the standard method for the sediment analysis. The PLE method
      showed a precision (average RSD ranged from 6 to 33%) and an accuracy (average
      recovery 85 and 87% for 4-NP and 4-NPE, respectively) comparable to those of
      Soxhlet. The extraction was performed on river sediments and no organic carbon
      content influence was found. The comparative study presented in this paper
      demonstrates that PLE is an alternative suitable extraction method for 4
      nonylphenol and 4-nonylphenol ethoxylate determination in sediments.

PMID- 11519815
TI  - Application of self-organizing maps for the classification of chromatographic
      systems and prediction of values of chromatographic quantities.
AB  - The applicability of self-organizing maps (SOM) for the classification of
      chromatographic systems or components of chromatographic systems based on data
      taken from literature is shown. The SOM approach is compared to dendrogram and
      principal components analysis (PCA) approaches. It has been shown that the
      distance between classified objects could reveal linear correspondence with
      quantity to be optimized, e.g. resolution, so it can be applied in the
      chromatographic method development. SOMs can also be applied for prediction of
      chromatographic quantities. It is shown that SOM-based response surface modeling
      is comparable to triangular presentation of mobile phase composition response
      surfaces.

PMID- 11519816
TI  - Comparison of L-tryptophan binding capacity of BSA captured by a polymer brush
      with that of BSA adsorbed onto a gel network.
AB  - A polymer brush containing a diethylamino group as an anion-exchange group was
      appended onto a polymer substrate by radiation-induced graft polymerization and
      subsequent chemical modifications. Bovine serum albumin as a chiral ligand for L
      tryptophan was bound to the polymer brush at a density ranging from 17 to 150 g
      BSA/l. For comparison, BSA was adsorbed onto the gel network containing a
      diethylaminoethyl group. The molar binding ratio of L-tryptophan to BSA on the
      polymer brush was 1.7-fold higher than that to BSA on the gel network.

PMID- 11519817
TI  - Dependence of reversed-phase retention of ionizable analytes on pH, concentration
      of organic solvent and silanol activity.
AB  - In reversed-phase chromatography, the retention of ionizable analytes is
      influenced by the ionic properties of the packing caused by surface silanol
      groups. We have measured the ion-exchange properties of both reversed-phase
      bonded phases and their underlying base materials. The probe used in this part of
      the study was bretylium tosylate. The acquired knowledge is then used for a
      complete and quantitative understanding of the retention behavior of ionizable
      compounds as a function of the pH of the mobile phase and the solvent
      composition. We have studied the retention pattern of a broad range of acids,
      bases, and polyfunctional analytes over the pH range from 2 to 11 and from water
      to 80% acetonitrile. A few application examples demonstrate the relevant
      findings.

PMID- 11519819
TI  - Analysis of sulfobutyl ether-beta-cyclodextrin mixtures by ion-spray mass
      spectrometry and liquid chromatography-ion-spray mass spectrometry.
AB  - The analysis of two commercial and two home-made sulfobutyl ether beta
      cyclodextrin (SBE-beta-CD) samples by ion-spray (IS) mass spectrometry and by
      liquid chromatography-mass spectrometry coupling (LC-MS) is investigated in a
      negative ion mode. SBE-beta-CD fragmentation was first investigated by direct
      infusion. In IS, the best conditions for SBE-beta-CD ionization consisted of
      ammonium acetate added to an acetonitrile/water mixture as sample solvent. These
      conditions allowed simplification of the mass spectrum, mainly by the formation
      of dicharged species [M-2H]2-, thus limiting the production of multicharged
      fragments. IS-MS permits fast and simple measurement of the substitution pattern
      and determination of the global degree of substitution for SBE-beta-CD mixtures.
      A complementary method using LC-MS was developed for the analysis of these
      mixtures. The substitution patterns obtained by LC-MS are in good agreement with
      those determined by direct MS analysis. The LC-MS coupling enabled separation of
      the mixtures versus the charge in anion-exchange chromatography (AEC) whereas no
      separation of the different substitution isomers potentially present in the SBE
      beta-CD mixture was displayed. The AEC methodology described can be successfully
      used for fractionation of SBE-beta-CD derivatives at the semi-preparative scale.

PMID- 11519818
TI  - Continuous superporous agarose beds in radial flow columns.
AB  - Continuous superporous agarose beds constitute a new support material for
      chromatography, biocatalysis and electrophoresis. The bed consists of a single
      piece of agarose gel, homogeneously transected by flow-carrying pores, which
      easily can be varied in the range of 10-100 microm. In this work, large diameter
      beds (60 mm) were prepared and used in specially designed radial flow columns.
      The basic chromatographic properties of the beds were investigated by size
      exclusion chromatography experiments. In an affinity chromatography application
      one bed was derivatized with Cibacron Blue 3GA and used for the purification of
      lactate dehydrogenase from a crude bovine heart extract. In a biotransformation
      application one bed was provided with immobilized beta-galactosidase and used in
      the production of lactose-free milk.

PMID- 11519820
TI  - Efficient enantioselective separation of drug enantiomers by immobilised antibody
      fragments.
AB  - There is an increasing need for methods for efficient enantioselective separation
      and purification of chiral drugs. Genetic engineering provides the means for
      generating recombinant antibodies exhibiting extremely high specificity for even
      small molecular mass compounds. Here, recombinant antibody fragments have been
      generated for the drug diarylalkyltriazole that contains two chiral centres.
      Immobilised antibody fragments has been used successfully for efficient, step
      wise separation of two enantiomers of the drug. Owing to the antibody
      specificity, one enantiomer came out in the flow-through, while the bound
      enantiomer could be specifically eluted. One of the antibodies tolerated solvents
      required both for dissolving the target molecules and for their elution for
      extended times and was shown to function over multiple cycles of the separation
      process.

PMID- 11519821
TI  - Effect of ion-exchange site and eluent modifiers on the anion-exchange of
      carboxylic acids.
AB  - The chromatographic behavior of carboxylic acids has been investigated, on three
      different latex-based anion-exchange columns, in order to define the effect of
      the ion-exchange site structure on selectivity. The analytical columns produced
      are characterized by alkyl amines containing zero, one or two hydroxyl groups on
      the anion-exchange functional site. Divalent carboxylic acids, namely fumaric,
      maleic, trans-beta-hydromuconic, trans,trans-muconic, oxalic, malonic, succinic,
      glutaric, adipic, malic, tartaric and mucic acids, have been chosen as test
      solutes. The performance of the three stationary phases has been studied
      employing NaOH eluents and has been discussed with respect to the different
      hydrophilicity of the ion-exchange sites and analytes. Considering on previous
      results obtained using organic solvents (methanol and acetonitrile) with
      carbonate eluents on a highly hydrophilic column, the performance of the three
      exchangers has also been studied using acetonitrile, methanol and n-propanol. The
      chromatographic behavior was similar for the three columns studied, but the
      different organic solvents gave variations in selectivity. In order to
      characterize these differences, particle size measurements of the latices were
      performed both in pure water and in the presence of each organic solvent studied.

PMID- 11519822
TI  - Modulation of DNA synthesis by muscarinic cholinergic receptors.
AB  - Acetylcholine muscarinic receptors are a family of five G-protein-coupled
      receptors widely distributed in the central nervous system and in peripheral
      organs. Activation of certain subtypes of muscarinic receptors (M1, M3, M5) has
      been found to modulate DNA synthesis in a number of cell types. In several cell
      types acetylcholine, by activating endogenous or transfected muscarinic
      receptors, can indeed elicit cell proliferation. In other cell types, however, or
      under different experimental conditions, activation of muscarinic receptors has
      no effect, or inhibits DNA synthesis. A large number of intracellular pathways
      are being investigated to define the mechanisms involved in these effects of
      muscarinic receptors; these include among others, phospholipase D, protein
      kinases C and mitogen-activated-protein kinases. The ability of acetylcholine to
      modulate DNA synthesis through muscarinic receptors may be relevant in the
      context of brain development and neoplastic growth.

PMID- 11519823
TI  - Up-regulated expression of HGF in rat liver cells after experimental endotoxemia:
      a potential pathway for enhancement of liver regeneration.
AB  - A lipopolysaccharide (LPS)-induced inflammation prior to an hepatic resection has
      been shown to enhance liver regeneration in rat. The aim of the present study was
      to investigate the expression of hepatocyte growth factor (HGF) and its c-Met
      receptor under such experimental conditions. Animals were submitted to a two
      third hepatectomy or a LPS challenge carried out 12 h prior to resection. Non
      parenchymal and parenchymal cells were isolated from livers obtained at various
      times post-hepatectomy. Quantitative RT-PCR for HGF and c-Met mRNAs were
      performed from total liver or purified cell fractions and HGF mRNA was also
      analyzed by in situ RT-PCR on liver sections. A LPS challenge alone induced a
      marked up-regulation of HGF mRNA level in whole liver and isolated hepatocytes.
      Furthermore, when partial hepatectomy (PH) was preceded by a LPS challenge, an
      increase of HGF mRNA level was seen in whole liver and contrasted with a
      decreased level in non parenchymal cells. These results were confirmed by in situ
      RT-PCR. In isolated hepatocytes from endotoxemic rats, the mRNA level for the LPS
      specific membranous receptor mCD14 was markedly up-regulated and even more so
      when LPS was followed by PH. Moreover, a TNFalpha challenge alone induced an up
      regulation of HGF mRNA in hepatocytes and a down-regulation in non parenchymal
      cells (NPCs). Overall, when a LPS challenge is given prior to PH the major source
      of hepatic HGF appears to be the hepatocyte itself rather than NPCs. An autocrine
      HGF/c-Met loop which promotes the proliferative potential of the hepatic
      parenchymal cell and participates in liver regeneration is postulated.

PMID- 11519824
TI  - GDF-8 propeptide binds to GDF-8 and antagonizes biological activity by inhibiting
      GDF-8 receptor binding.
AB  - GDF-8 is a new member of the TGF-beta superfamily which appears to be a negative
      regulator of skeletal muscle mass. Factors which regulate the biological activity
      of GDF-8 have not yet been identified. However, the biological activities of TGF
      beta superfamily members, TGF-beta1, -beta2 and -beta3, can be inhibited by
      noncovalent association with TGF-beta1, -beta2 and beta3 propeptides cleaved from
      the amino-termini of the TGF-beta precursor proteins. In contrast, the
      propeptides of other TGF-beta superfamily members do not appear to be inhibitory.
      In this investigation, we demonstrate that purified recombinant GDF-8 propeptide
      associates with purified recombinant GDF-8 to form a noncovalent complex, as
      evidenced by size exclusion chromatography and chemical crosslinking analysis.
      Furthermore, we show that GDF-8 propeptide inhibits the biological activity of
      GDF-8 assayed on A204 rhabdomyosarcoma cells transfected with a (CAGA)12 reporter
      construct. Finally, we demonstrate that GDF-8 propeptide inhibits specific GDF-8
      binding to L6 myoblast cells. Collectively, these data identify the GDF-8
      propeptide as an inhibitor of GDF-8 biological activity.

PMID- 11519825
TI  - Engineering, expression, and renaturation of a collagen-targeted human bFGF
      fusion protein.
AB  - Basic fibroblast growth factor (bFGF) is a potent in vitro mitogen for capillary
      endothelial cells, stimulates angiogenesis in vivo, and may participate in tissue
      repair. Basic FGF is found in abundance in tissues such as brain, kidney and
      cartilage. This study reports the expression, purification, and renaturation of a
      biologically active human basic fibroblast growth factor fusion protein (hbFGF
      F1) from Escherichia coli. A prokaryotic expression vector was engineered to
      produce a tripartite fusion protein consisting of (i) a purification tag, (ii) a
      protease-sensitive linker/collagen-binding domain, and (iii) cDNA sequence
      encoding the active fragment of hbFGF. The expressed hbFGF-F1 and hbFGF-F2 (it
      contains a collagen-binding domain), located in inclusion bodies, were
      solubilized with 6 M guanidine-HCl and renatured using a glutathione redox system
      and protracted dialysis under various experimental conditions. The purification
      of the recombinant proteins was achieved by binding the His-tag of the fusion
      protein on a Ni-NTA metal chelate column. The biological activity of the
      recombinant growth factors was demonstrated by their ability to stimulate
      proliferation of human vein endothelial cells (HVEC), monitored by [3H]-thymidine
      incorporation, where commercial recombinant human bFGF (rhbFGF) served as a
      positive control. Purified rhbFGF-F1 and rhbFGF-F2 constructs exhibited
      proliferative activity comparable to commercial rhbFGF. Binding of the renatured
      hbFGF-F2 fusion protein to collagen was demonstrated by stable binding on a
      collagen-conjugated Sephadex-G15 column. The high affinity binding was also
      demonstrated by the binding of [3H]-collagen to the rhbFGF-F2 protein immobilized
      on a Ni-NTA column. The rhbFGF-F2 fusion protein bound to collagen coated
      surfaces with high affinity but exhibited comparatively lower biological activity
      than the fusion protein in solution, suggesting a potentially latent
      configuration. Taken together, these results demonstrate that biologically active
      rhbFGF fusion proteins can be recovered from transformed bacteria by oxidative
      refolding; thus, providing a means for its high-yield production, purification,
      and renaturation from microorganisms. Furthermore, we demonstrate that the
      auxiliary collagen-binding domain effectively targets the recombinant growth
      factor to type I collagen. The clinical effect of rhbFGF-F2 on wound healing is
      also studied in streptozotocin-induced diabetic rats and evaluated by
      histological examination comparing with rhbFGF-F1 and commercial bFGF effects.
      The highly beneficial effects of rhbFGF-F2 on wound healing is suggested to be
      due to its extremely potent angiogenesis and granulation tissue formation
      activities, leading to a rapid reepithelialization of the wound. Topical
      application of rhbFGF-F2 mixed with type I collagen is a more effective method in
      accelerating closure of full-thickness excisional skin-wound in diabetic rats
      when compared with the fusion protein alone or commercial hbFGF at the same
      doses. These studies advance the technology necessary to generate large
      quantities of targeted bFGF fusion proteins as well as to develop new strategies
      for specific biomedical applications.

PMID- 11519826
TI  - The comparative release of FGF1 by hypoxia and temperature stress.
AB  - The signal peptide-less FGF gene family prototype, FGF1 is released in response
      to temperature stress in vitro as a latent reducing agent-sensitive homodimer non
      covalently complexed with the extravesicular p40 domain of p65 synaptotagmin
      (Syt)1. Because FGF1 is well recognized as an angiogenesis factor in vivo and
      angiogenesis is known to be induced by hypoxia, we examined the release of FGF1
      and p40 Syt1 under conditions of hypoxia and temperature stress using a
      chemostatic microcarrier cell culture system. We report that like the pathway
      used by FGF1 and p40 Syt1 release under temperature stress, hypoxia also induces
      the release of FGF1 and p40 Syt1 with similar kinetic and pharmacologic
      properties including the requirement for functional cysteine residues. Lastly,
      FGF1 and p40 Syt1 release in response to hypoxia and temperature stress is
      sensitive to lipoxygenase and cyclooxygenase inhibitors suggesting that
      arachidonic acid metabolism may play an important role in the mechanism of FGF1
      release in vitro.

PMID- 11519827
TI  - The role of vascular endothelial growth factor in the tissue specific in vivo
      growth of prostate cancer cells.
AB  - Despite the fact that cancer cells can be found in many vascular beds, continued
      growth of the metastatic tumor focus exhibits a significant degree of 'organ
      tropism', with only certain organs exhibiting the ravages of metastatic disease.
      Since a limiting factor to the growth of metastases beyond 2 mm in diameter, may
      be a lack of angiogenesis, we sought to determine whether tumor overexpression of
      vascular endothelial growth factor (VEGF), a potent angiogenic factor related to
      prostate cancer metastasis, is causally related to organ specific tumor growth in
      a prostate cancer xenograft model. LnCaP-C4-2 is a subline of the human prostate
      cancer cell line LnCaP which unlike its parent, has a predilection for growth in
      bone, a common site for human prostate cancer metastasis. LnCaP-C4-2, is
      tumorigenic when injected intrafemorally in mice but requires co-injection of
      stromal components (Matrigel) to be tumorigenic in the subcutaneous site. Because
      of this site-specific tumorigenicity profile and relatively low VEGF mRNA and
      protein expression, this line was transfected with a full length cDNA encoding
      the 165 isoform of VEGF. Cells either overexpressing or not expressing the
      transfected gene were selected for study in vivo and in vitro. Overexpression of
      VEGF did not seem to affect in vitro cell growth. Such overexpression did affect
      tumorigenicity and in vivo tumor growth rates when cells were inoculated in the
      subcutaneus site. Interestingly, the dependency of subcutaneous tumorigenicity on
      Matrigel co-inoculation was still observed in cells overexpressing VEGF. In
      contrast to the impact that VEGF overexpression has on subcutaneous
      tumorigenicity, no such effect was observed when cells were inoculated in
      orthotopic/prostate (primary) or intrafemoral (metastatic) sites. In view of the
      importance of tumor-stromal interactions in growth of xenografts, we sought to
      determine if the host strain is important to the observed tumorigenicity effects
      of VEGF overexpression. No differences in subcutaneous tumorigenicity as a
      function of either Matrigel use or VEGF expression levels were observed when
      SCID/bg and RAG/pfp mouse strains were compared. In conclusion, our data indicate
      that the biological impact of prostate tumor VEGF overexpression is organ/site
      specific, leading to the speculation that it may play a part in the observed
      organ tropism of metastatic spread. In addition, these results highlight the
      importance of the tumor microenvironment in determining the biological impact of
      transfected and overexpressed genes in the study of tumor biology.

PMID- 11519829
TI  - Peculiarities of the rodent subcutaneous space for testing of bone inducing
      agents.

PMID- 11519828
TI  - Characterization of the Epha1 receptor tyrosine kinase: expression in epithelial
      tissues.
AB  - The Eph family of receptor tyrosine kinases plays a crucial role during
      development and is implicated in oncogenesis. Using a partial cDNA clone of an
      Eph-related kinase (Esk) we isolated the complete coding region of a gene which
      we show to be murine EphA1 by both structural and functional criteria. The
      chromosomal localization is shown to be syntenic to hEphA1 and the genomic
      organization also shows distinct features found in the hEphA1 gene. Functionally,
      in keeping with findings for the human homologue, both soluble recombinant and
      "native" mEphA1 show preferential binding to ephrin A1. However, we also observed
      significant binding to other A-type ligands as has been observed for other Eph
      receptors. We analysed the expression of mEphA1 mRNA by in situ hybridization on
      tissue sections. mEphA1 was expressed in epithelial elements of skin, adult
      thymus, kidney and adrenal cortex. Taken together with previous Northern blotting
      data these results suggest that mEphA1 is expressed widely in differentiated
      epithelial cells.

PMID- 11519830
TI  - TT virus: virological and genomic characteristics and disease associations.

PMID- 11519831
TI  - Effect of prepyloric gastric transection and anastomosis on sphincter of Oddi
      cyclic motility in conscious dogs.
AB  - PURPOSE: We previously reported significant changes in sphincter of Oddi cyclic
      motility after proximal duodenal transection and anastomosis. However, the role
      of intrinsic myoneural continuity between the antrum and duodenum in this respect
      is not understood. The aim of this study was to elucidate the effects of
      prepyloric gastric transection on sphincter of Oddi motility in animals in the
      conscious state. METHODS: Pressures in the bile duct, duodenum, stomach, and
      sphincter of Oddi and their response to an injection of cholecystokinin
      octapeptide were measured in four conscious dogs, with a duodenal cannula, before
      and after gastric transection and anastomosis 1.5 cm proximal to the pylorus.
      RESULTS: Gastric transection did not affect the initiation and propagation of the
      gastroduodenal migration motor complex. Biliary pressure (5.7 +/- 0.15 to 5.5 +/-
      0.2 mmHg; P = 0.91), sphincter of Oddi basal pressure (10.6 +/- 0.3 to 10.7 +/-
      0.2 mmHg; P = 0.97), and amplitude (26.0 +/- 1.2 to 32.9 +/- 1.7 mmHg; P = 0.304)
      did not change after gastric transection. Biliary pressure decreased from phase
      II to phase III of the duodenal migrating motor complex. Cholecystokinin
      octapeptide inhibited sphincter of Oddi phasic waves before and after gastric
      transection. CONCLUSIONS: Intrinsic myoneural transection at the prepyloric
      region does not influence sphincter of Oddi cyclic motility. Preservation of
      pyloroduodenal myoneural continuity in pylorus-preserving gastrectomy would be
      beneficial to maintain normal sphincter of Oddi motility.

PMID- 11519832
TI  - Gastric emptying and orocecal transit time in pregnancy.
AB  - PURPOSE: To evaluate the effects of pregnancy on gastrointestinal function, we
      determined gastric emptying time, orocecal transit time, and fasting
      gastrointestinal hormone levels (cholecystokinin, gastrin, pancreatic
      polypeptide, neurotensin) in 11 women with mild dyspeptic symptoms during the
      first and third trimesters of their pregnancies, and again 4-6 months after
      delivery. METHODS: After the women ingested a disaccharide solution, orocecal
      transit time was determined by monitoring breath hydrogen concentrations at 10
      min intervals, and values were compared with the postpartum value. Ultrasound
      examinations of gastric emptying were performed during the same intervals.
      RESULTS: The half-emptying time and the final gastric emptying time did not
      differ in the first and third trimesters and postpartum, but gastrointestinal
      transit time was significantly longer in the third trimester of pregnancy than
      postpartum (100.0 min [range, 50.5-240.0 min] vs 70.0 min [range, 40.5-240.0 min;
      P < 0.05]), respectively. Mean plasma pancreatic polypeptide values were lower in
      the third trimester of pregnancy than postpartum. and a negative correlation was
      observed between pancreatic polypeptide levels and transit time in the third
      trimester (r = -0.65; P = 0.0261). The plasma levels of other gastrointestinal
      hormones did not differ in the various periods studied. CONCLUSIONS: Our study
      shows that, despite evident dyspeptic symptoms, there were no significant
      alterations in gastric emptying or orocecal transit time during the first
      trimester of pregnancy. Conversely, in the third trimester, orocecal transit time
      was significantly longer.

PMID- 11519833
TI  - Th1/Th2 cytokine profiles and their relationship to clinical features in patients
      with chronic hepatitis C virus infection.
AB  - PURPOSE: An imbalance in helper T-cell type 1 (Th1) and type 2 (Th2) cytokines is
      suggested to play an important role in the pathogenesis of chronic viral
      infections, but this issue is not resolved in patients with hepatitis C virus
      (HCV) infection. The aim of this study was to clarify the relationship between
      the balance of Th1 and Th2 cytokines and liver damage. METHODS: We investigated
      cytokine levels in the peripheral blood and liver tissue of patients with chronic
      HCV infection (n = 59) by three different methods; we used flow cytometry to
      detect intracellular cytokines, and we measured cytokine titers in sera and in
      the supernatants of lymphocyte cultures with enzyme-linked immunosorbent assays
      (ELISAs). RESULTS: In both CD4+ and CD8+ cells, interferon (IFN) gamma-producing
      cell populations increased, while there was no difference in interleukin (IL)-10
      production, indicating a shift to a Th1 cytokine profile with the progression of
      liver disease. With respect to the ratio of IFN-gamma to IL-10, a correlation was
      found in CD4+ cells between peripheral blood and liver tissue (r = 0.98; P =
      0.0011). Th1 cytokine was predominant in intrahepatic CD4+ cells, while it was
      predominant in peripheral blood CD8+ cells. CONCLUSIONS: These findings indicate
      a correlation between dominant Th1 response and disease activity and progression.
      In addition, we suggest that intrahepatic CD4+ T cells play a pathogenetic role
      in the hepatic injury of HCV infection.

PMID- 11519834
TI  - Liver abscess in patients with cirrhosis of the liver: a 12-year experience.
AB  - PURPOSE: Liver abscess is rare in patients with cirrhosis of the liver. The aim
      of this retrospective study was to investigate the incidence, clinical
      presentation, causal pathogens, and outcome of liver abscess in cirrhotic
      patients. METHODS: We collected 21 liver abscess specimens (from 14 male patients
      and 7 female patients; Child A: B: C, 4: 7: 10) from 22,731 admissions of 6450
      cirrhotic patients, from 1986 through 1998. RESULTS: The common clinical symptoms
      and signs included fever, chills, and abdominal tenderness. The major
      predisposing factors were biliary tract disease (52%) and diabetes mellitus
      (48%). The diagnosis rate with abdominal ultrasonography was 79%. Gram-negative
      aerobes were the predominant pathogens (Klebsiella pneumoniae, 66.7%; Escherichia
      coli, 23.8%), and occurred in 80% and 69% of blood and pus cultures,
      respectively, while 38% of cases showed polymicrobial pathogens. The location of
      the abscess was predominantly in the right lobe (71.4%), and 47.6% of patients
      had multiple abscesses. Six patients died (all with Child C cirrhosis). The
      overall mortality rate was 28.6% (6/21). CONCLUSIONS: The incidence of liver
      abscess in the cirrhotic patients was low, at 0.09% (21/22,731 admissions). The
      clinical presentations and pathogens were not different from those in
      noncirrhotic patients, except that in our cirrhotic patients, there was no
      significant difference in mortality between those with monomicrobial and those
      with polymicrobial abscess: nor was there a significant difference in mortality
      between those with single and those with multiple abscesses. The Child C patients
      were the high-risk group.

PMID- 11519835
TI  - Contrast-enhanced intraductal ultrasonography for thickened bile duct wall.
AB  - PURPOSE: We carried out this study to evaluate the usefulness of contrast
      enhanced intraductal ultrasonography (ceIDUS) in the differentiation of thickened
      bile duct wall at the hepatic bifurcation caused by malignant tumor from that
      caused by cholangitis. METHODS: Seven patients (two with primary sclerosing
      cholangitis [PSC], one with secondary sclerosing cholangitis [SSC], and four with
      bile duct carcinomas [BDC] at the hepatic bifurcation underwent endoscopic
      ceIDUS, in which we used Levovist. The recorded images of echo-brightness were
      analyzed histographically. RESULTS: The bile duct wall, in PSC and SSC, but not
      in BDC, was enhanced by Levovist. CONCLUSION: ceIDUS with histographic analysis
      may be useful for distinguishing thickened bile duct wall caused by malignant
      tumor from that caused by cholangitis.

PMID- 11519836
TI  - Esophagectomy and hepatic arterial chemotherapy following hepatic resection for
      esophageal cancer with liver metastasis.
AB  - We report a patient who had simultaneous transthoracic esophagectomy and hepatic
      arterial cannulation for chemotherapy following hepatic resection for esophageal
      cancer with solitary liver metastasis. He had an uneventful postoperative course
      and received two cycles of postoperative arterial chemotherapy with cisplatinum
      and 5-fluorouracil. He developed multiple liver metastases 6 months after the
      surgery. He has been receiving arterial chemotherapy at the outpatient department
      and is alive 15 months after the surgery. Aggressive esophagectomy and hepatic
      arterial chemotherapy is the treatment of choice for esophageal cancer with liver
      metastasis when unresectable metastases are confined to the liver.

PMID- 11519837
TI  - Alcoholic liver cirrhosis complicated with torsade de pointes during plasma
      exchange and hemodiafiltration.
AB  - A 36-year-old man with severe alcoholic hepatitis was treated with plasma
      exchange combined with hemodiafiltration to remove endotoxins and inflammatory
      cytokines. During the treatment, he had critical arrhythmia (torsade de pointes
      [TdP]). His laboratory data showed hypomagnesemia, which was suspected to be
      responsible for the development of TdP. Patients with alcoholic liver disease
      tend to have hypomagnesemia and Q-T interval prolongation. Furthermore,
      hemodiafiltration may cause hypomagnesemia. Careful observation for electrolytic
      imbalance is necessary when clinicians treat patients with alcoholic liver
      failure with a liver support system.

PMID- 11519838
TI  - Thrombotic thrombocytopenic purpura in autoimmune hepatitis.
AB  - A 19-year-old woman presented with clinical manifestations of sudden, fulminant
      thrombotic thrombocytopenic purpura associated with autoimmune hepatitis and
      autoimmune thrombocytopenic purpura. Although thrombotic thrombocytopenic purpura
      may, rarely, be associated with systemic lupus erythematosus and other autoimmune
      diseases, to our knowledge, the syndrome has never been described in association
      with autoimmune hepatitis. In this patient, too, the etiology of thrombotic
      thrombocytopenic purpura associated with autoimmune disease remains elusive. The
      patient was treated with corticosteroid, which brought about no improvement in
      her condition, and she died of multiorgan failure. Diagnosis is challenging, but
      prompt diagnosis is necessary because thrombotic thrombocytopenic purpura is a
      life-threatening syndrome whose prognosis has been improved significantly by
      early plasmapheresis treatment.

PMID- 11519839
TI  - Portal vein thrombosis associated with antiphospholipid syndrome.
AB  - Portal vein thrombosis is a rare occurrence, and often an underlying
      hypercoagulable state can be found. Recently, there has been growing interest and
      recognition of the antiphospholipid syndrome in association with acquired
      hypercoagulable state. This syndrome consists of the association of lupus
      anticoagulant or antiphospholipid antibodies with arterial or venous thrombosis,
      thrombocytopenia, and spontaneous abortion. We report a case of portal vein
      thrombosis associated with the antiphospholipid syndrome. In our patient, chronic
      liver disease, hepatobiliary infection, abdominal malignancies,
      myeloproliferative disorders, and inherited coagulation disorders were excluded.
      This case report suggests that serum antiphospholipid antibodies should be
      investigated in patients with portal vein thrombosis of unexplained etiology.

PMID- 11519840
TI  - Helicobacter pylori infection does not affect serum leptin concentration and body
      mass index (BMI) in asymptomatic subjects.

PMID- 11519841
TI  - Who respects physiology, and who will be rewarded?

PMID- 11519842
TI  - Is contrast-enhanced intraductal ultrasonography helpful in the differential
      diagnosis of a thickened bile duct wall?

PMID- 11519843
TI  - AIDS policy modeling for the 21st century: an overview of key issues.
AB  - Decisions about HIV prevention and treatment programs are based on factors such
      as program costs and health benefits, social and ethical issues, and political
      considerations. AIDS policy models--that is, models that evaluate the monetary
      and non-monetary consequences of decisions about HIV/AIDS interventions--can play
      a role in helping policy makers make better decisions. This paper provides an
      overview of the key issues related to developing useful AIDS policy models. We
      highlight issues of importance for researchers in the field of AIDS policy
      modeling as well as for policy makers. These include geographic area, setting,
      target groups, interventions, affordability and effectiveness of interventions,
      type and time horizon of policy model, and type of economic analysis. This paper
      is not intended to be an exhaustive review of the AIDS policy modeling
      literature, although many papers from the literature are discussed as examples;
      rather, we aim to convey the composition, achievements, and challenges of AIDS
      policy modeling.

PMID- 11519844
TI  - Managed care, vertical integration strategies and hospital performance.
AB  - OBJECTIVE: The purpose of this study is to examine the association of managed
      care with hospital vertical integration strategies, as well as to observe the
      relationships of different types of vertical integration with hospital efficiency
      and financial performance. DATA AND METHODS: The sample consists of 363
      California short-term acute care hospitals in 1994. Linear structure equation
      modeling is used to test six hypotheses derived from the strategic adaptation
      model. Several organizational and market factors are controlled statistically.
      PRINCIPAL FINDINGS: Results suggest that managed care is a driving force for
      hospital vertical integration. In terms of performance, hospitals that are
      integrated with physician groups and provide outpatient services (backward
      integration) have better operating margins, returns on assets, and net cash flows
      (p < 0.01). These hospitals are not, however, likely to show greater
      productivity. Forward integration with a long-term-care facility, on the other
      hand, is positively and significantly related to hospital productivity (p <
      0.001). Forward integration is negatively related to financial performance (p <
      0.05), however, opposite to the direction hypothesized. CONCLUSIONS: Health
      executives should be responsive to the growth of managed care in their local
      market and should probably consider providing more backward integrated services
      rather than forward integrated services in order to improve the hospital's
      financial performance in today's competitive health care market.

PMID- 11519845
TI  - Measuring efficiency of long-term care units in Finland.
AB  - Data Envelopment Analysis (DEA) was used to measure the nursing care efficiency
      of 64 long-term care units in Finland. New approaches introduced for evaluating
      efficiency were unit/ward level analysis, and the case-mix classification
      Resource Utilization Groups (RUG-III). Efficiency determinations were based on
      four DEA measures: cost, technical, allocative, and scale efficiency. The results
      indicated considerable variation in efficiency between units, suggesting that
      efficiency could be improved through better management and allocation of
      resources. Larger units seemingly operated more efficiently than smaller units.
      Allocative inefficiency resulted from using too many registered nurses and aides,
      and too few licensed practical nurses.

PMID- 11519846
TI  - A quality-adjusted cost function in a regulated industry: the case of Dutch
      nursing homes.
AB  - The primary objective of this paper is to examine the cost structure of the Dutch
      nursing home industry, using econometric techniques. In this paper we present a
      model that combines economic behaviour and quality of services measured by a
      latent variable. We propose a simple method for identifying and estimating cost
      functions in the presence of endogenous, unobserved quality. Estimating this
      quality-adjusted cost function and the corresponding cost share equations
      indicates that quality is negatively related to the input prices of nurses and
      other personnel, indicating that nursing homes have a preference for labour. We
      also show that the quality-adjusted model is superior to a model with exogenous
      quality.

PMID- 11519847
TI  - Modeling emotion and behavior in animated personas to facilitate human behavior
      change: the case of the HEART-SENSE game.
AB  - The goal of this research is to determine whether a computer based training game
      (HEART-SENSE) can improve recognition of heart attack symptoms and shift
      behavioral issues so as to reduce pre-hospitalization delay in seeking treatment.
      Since treatment delay correlates with adverse outcomes, this research could
      reduce myocardial infarction mortality and morbidity. In Phase I we created and
      evaluated a prototype virtual village in which users encounter and help convince
      synthetic personas to deal appropriately with a variety of heart attack scenarios
      and delay issues. Innovations made here are: (1) a design for a generic simulator
      package for promoting health behavior shifts, and (2) algorithms for animated
      pedagogical agents to reason about how their emotional state ties to patient
      condition and user progress. Initial results show that users of the game exhibit
      a significant shift in intention to call 9-1-1 and avoid delay, that multi-media
      versions of the game foster vividness and memory retention as well as a better
      understanding of both symptoms and of the need to manage time during a heart
      attack event. Also, results provide insight into areas where emotive pedagogical
      agents help and hinder user performance. Finally, we conclude with next steps
      that will help improve the game and the field of pedagogical agents and tools for
      simulated worlds for healthcare education and promotion.

PMID- 11519848
TI  - Determinants of information technology outsourcing among health maintenance
      organizations.
AB  - We analyze the determinants of HMO information technology outsourcing using two
      studies. Study 1 examines the effect of asset specificity on outsourcing for
      development and operation activities, using HMO specific fixed effects to control
      for differences between HMOs. Study 2 regresses the HMO specific fixed effects
      from Study 1, which measure an HMO's propensity to outsource, on HMO
      characteristics. The data comes from a 1995 InterStudy survey about information
      technology organization of HMOs. While HMOs split roughly equally in outsourcing
      information technology development activities, they are extremely unlikely to
      outsource the day-to-day operation of information systems. The greater an HMO's
      information technology capability and the complexity of information systems
      supported, the less likely is an HMO to outsource. While HMOs less than two years
      old, for-profit HMOs, local or Blue Cross-affiliated HMOs, and mixed HMOs are
      more likely to outsource, federally qualified HMOs are less likely to outsource.
      Policy and managerial implications for the adoption and diffusion of new ways of
      organizing information technology, such as application service providers (ASPs),
      are discussed.

PMID- 11519850
TI  - Migration pathways of human glioblastoma cells xenografted into the
      immunosuppressed rat brain.
AB  - Diffuse invasion of the brain by tumor cells is a hallmark of human glioblastomas
      and a major cause for the poor prognosis of these tumors. This phenomenon is only
      partially reproduced by rodent models of gliomas that display a very high rate of
      proliferation and limited cell migration. We have analyzed the development of
      human glioblastoma cells (GL15) xenografted into the brain of immunosuppressed
      rats, in order to define the characteristics of tumor cell invasion. As
      identified by the specific immunolabeling of the tumor cells for the human HLA
      ABC antigen, GL15 tumors reproduced the three types of intraparenchymal invasion
      observed in patients. First, a majority of multipolar tumor cells intermingled
      rapidly and profusely with host neural cells in the margin of the injection site.
      This progressively enlarging area was principally responsible for the tumor
      growth over time. Second, in the gray matter, columns of thin bipolar tumor cells
      aligned along capillary walls. Third, in the white matter, elongated bipolar
      isolated tumor cells were observed scattered between axonal fibers. The maximum
      migration distances along white matter fibers remained significantly higher than
      the maximum migration distances along blood vessels, up to two months after
      injection. Development of the tumor was associated with a significant increase of
      vascularization in the area of tumor spread. Xenografting of human GL15
      glioblastoma cells into the immunosuppressed rat brain allowed to differentiate
      between the three classical types of invasion identified in the clinic, to
      quantify precisely the distances of migration, and to evaluate cell morphology
      for each of these routes. The present results support the existence of host/tumor
      cells interactions with specific characteristics for each type of invasion.

PMID- 11519849
TI  - Genetic basis of pituitary adenoma invasiveness: a review.
AB  - Compatible with contemporary paradigms of the role of genetic aberrations in the
      progression of human tumors, the growth of pituitary tumors into a state of
      invasiveness appears to be due to genetic alterations. Amplification of H-ras and
      c-myc oncogenes and mutations of p53, nm23 and Rb genes have been identified
      disproportionately more in aggressive tumors and, in the case of Rb gene, in
      pituitary carcinomas, providing evidence that amplification of these oncogenes (H
      ras and c-myc) and inactivation of tumor suppressor genes (p53, nm23 and Rb) seem
      to be at least one mechanism by which pituitary tumors progress. The current
      level of management of invasive pituitary adenomas should become more
      comprehensive as the advances in our understanding of genetic basis of pituitary
      adenoma invasiveness becomes translated into development of novel chemotherapy or
      gene transfer technique.

PMID- 11519851
TI  - Biological behavior and tumorigenesis of subependymal giant cell astrocytomas.
AB  - In spite of the benign nature of subependymal giant cell astrocytomas (SEGAs),
      some show massive hemorrhage, rapid growth, and tumor recurrence. This led us to
      investigate the biological behavior, cell dynamics, and tumorigenesis of SEGAs.
      All patients (4 men and 3 women; age range, 6-27 years; mean, 13.6 years) had
      features of tuberous sclerosis complex and obstructive hydrocephalus. One patient
      had intratumoral bleeding. In two patients, sequential neuroimaging showed a
      subependymal nodule growing to become a SEGA. All underwent surgical resection
      without radiation therapy. One tumor recurred and was treated surgically. There
      were no postoperative deaths. The presence of cytologic atypia, mitoses and
      vascular proliferation had no implication in terms of the clinical course. MIB-1
      labeling indices were low (mean, 0.9), indicating low proliferative potential.
      Unexpectedly, bcl-2 staining was sparse and bax staining predominated in majority
      of cases. However, the mean value of terminal deoxynucleotidyl transferase
      mediated dUTP-biotin nick end labeling index was low. Immunohistochemically,
      tumors were positive for both glial and neuronal markers. In the majority of our
      cases, the expression of p53 was low. Only one tumor was focally positive for
      tuberin. SEGAs have low proliferative potential and apoptotic activity, and
      exhibit features of mixed glial-neuronal differentiation. In contrast to p53,
      tuberin is suggested to be the tumor suppressor in this tumor.

PMID- 11519852
TI  - Absence of germline and somatic p53 alterations in children with sporadic brain
      tumors.
AB  - Cancers of the central nervous system are the most common solid tumors of
      childhood. Although somatic alterations of the p53 tumor suppressor gene have
      been implicated in brain tumorigenesis, the role of germline p53 mutations in the
      development of childhood brain tumors has not been well defined. As a component
      of an ongoing extensive study of the epidemiology of childhood brain tumors, we
      prospectively examined the germline and tumor p53 gene status in 85 children
      without a family history of cancer who were diagnosed with a sporadic malignant
      central nervous system tumor. Using PCR/single-strand conformational polymorphism
      analysis and direct DNA sequencing, 85 children were screened for the presence of
      constitutional p53 sequence alterations in exons 2 and 4 through 11. No mutations
      were identified. Commonly reported sequence polymorphisms were observed at codon
      72, as well as in 2 other previously described nucleotide residues. Forty-four
      brain tumor samples were available for analysis and of these 40 were paired with
      peripheral blood. Once again, no p53 mutations were found. Of the 5 germline
      samples with the 2 common polymorphisms, only one had a paired tumor sample for
      comparison and the tumor contained the same alteration as the germline. Of note,
      one tumor, a PNET of the cerebellum (medulloblastoma), showed loss of
      heterozygosity at codon 72. We can conclude that the frequency of germline and
      somatic p53 mutations in sporadic childhood brain tumors is very low, probably
      less than 1%, and there is no need to screen these patients routinely for their
      germline p53 status. However, the potential significance of LOH at codon 72
      remains to be elucidated.

PMID- 11519853
TI  - Histological and genetic diagnosis of gliomatosis cerebri: case report.
AB  - Gliomatosis cerebri is considered grade III astrocytoma because of the short
      survival period of patients with this tumor, while the tumor histologically
      consists of widespread low grade astrocytoma cells. The authors tried to clarify
      this discrepancy by applying genetic analysis of the tumor. A 29-year-old man
      originally presented with mild headache and showed diffuse high intensity areas
      in both hemispheres and in the cerebellum by T2-weighted magnetic resonance
      imaging (MRI) without gadolinium-dimeglumine (Gd)-enhancement in T1-weighted
      imaging. Histological diagnosis was gliomatosis cerebri with diffuse grade II
      astrocytoma. Seven months after temporary improvement following irradiation and
      chemotherapy, he developed progressive mental deterioration, and died in one year
      after the surgery. At this time T1-weighted imaging showed Gd-enhanced lesions
      with enlargement only of the cerebellar tumor. Genetic analysis demonstrated
      positive FGFR 1 and less FGFR 2 mRNA in the tumor tissue, and FGFR 1 mRNA was
      beta type dominant. These results indicated that the genetic features of this
      tumor are similar to those of glioblastoma multiforme concerning FGFR expression.
      The authors conclude that genetic investigation of the tumor tissue is required
      to predict the prognosis of gliomatosis cerebri patients, in addition to imaging
      and histological examinations.

PMID- 11519854
TI  - Characteristic chromosomal aberrations in sporadic cerebellar hemangioblastomas
      revealed by comparative genomic hybridization.
AB  - Hemangioblastomas (HBs) of the central nervous system are benign tumors and occur
      as sporadic (sp) tumors (75%) or as a manifestation of the von Hippel-Lindau
      (VHL) disease (25%). VHL-disease is an autosomal dominant disorder characterized
      by HBs of the central nervous system and retina, renal cell carcinoma (RCC),
      phaeochromocytoma (PHEO), islet tumors of the pancreas, and endolympatic sac
      tumors as well as cysts and cystadenoma in the kidney, pancreas and epididymis.
      In VHL patients a large spectrum of germline mutations in the VHL gene has been
      detected. In spHBs VHL alleles are reported to be inactivated in up to 50% of the
      tumors. To our knowledge the involvement of other genes in spHBs has not been
      investigated. To elucidate the oncogenesis of spHBs, we performed CGH on 10 spHBs
      to screen for chromosomal imbalances throughout the entire tumor genome.
      Aberrations most frequently detected are losses of chromosomes 3 (70%), 6 (50%),
      9 (30%), and 18q (30%) and a gain of chromosome 19 (30%). Based on these
      frequencies and the co-occurrence of these aberrations in the analyzed tumors we
      hypothesize that loss of chromosome 3 (harboring the VHL gene) is an early event
      in the oncogenesis of spHBs, followed by loss of 6, and then losses of
      chromosomes 9, 18q and gain of chromosome 19. Comparison of the chromosomal
      imbalances in spHBs to those previously reported in RCCs and PHEOs reveals that
      the pathway of spHBs shows similarities to both the RCCs and PHEOs.

PMID- 11519855
TI  - Lack of evidence of osteo-medullary metastases at diagnosis in patients with high
      grade gliomas.
AB  - High grade gliomas usually show a transient response to standard therapy by
      radiation. A local evolution leads to patient death in most of the cases.
      Necropsic series suggest that metastatic evolution is rather frequent in lungs,
      lymph nodes, bones or bone marrow. Are these metastatic deposits present
      initially? The authors retrospectively reviewed the bone marrow smears performed
      in 20 patients and the bone scans in 10 patients with high grade gliomas at time
      of diagnosis. None of these investigations showed metastatic deposits. It is thus
      suggested that metastatic deposits are probably a late event in the natural
      history of high grade gliomas. However, if local treatment could reach local
      control, metastases would probably become a major problem. Thus definitive cure
      of high grade glioma may require multidisciplinary approach.

PMID- 11519856
TI  - Brain glioma and human leukocyte antigens (HLA)--is there an association.
AB  - Expression of human leukocyte antigens (HLA) is important for the immune response
      against infectious agents and malignant cells. Association of single HLA antigens
      or HLA haplotypes with disease has been investigated previously, and positive
      correlations between HLA and some cancers, such as cervical or nasopharyngeal
      carcinomas have been reported. In the present study, HLA antigen frequencies of
      65 adult Caucasian patients with low-grade, anaplastic, or malignant astrocytic
      glioma (WHO grades II-IV) were compared with 157 racially similar, asymptomatic
      control individuals. Both standard serologic and PCR techniques for HLA typing
      were employed for all patients and controls. Our results suggest a positive
      association between single HLA antigens and presence of symptomatic cerebral
      glioma. Compared with the control population, patients positive for HLA-A*25 had
      a 3.0-fold increased risk of glioma (p = 0.04), patients positive for HLA-B*27, a
      2.7-fold risk (p = 0.03), and patients positive for HLA-DRB1*15, a 2.2-fold risk
      (p = 0.03), whereas HLA-DRB1*07 was associated with a 0.4-fold decreased risk of
      glioma (p = 0.02). Occurrence rate of some HLA antigen combinations and estimated
      haplotypes was also different in glioma patients. Thus, HLA-DRB1*15:DRB5*(51)
      occurrence in combination with HLA-DRB1*11 was associated with a 13.4-fold
      increased risk of glioma (p = 0.001), and the incidence of HLA-Cw*6:DRB1*07 with
      a 0.2-fold decreased risk of glioma (p = 0.03). In conclusion, single HLA
      antigens and their combinations and estimated haplotypes are possibly
      significantly more or less frequent in persons developing symptomatic cerebral
      glioma during their adult life, compared with asymptomatic individuals.

PMID- 11519858
TI  - Shunt-related abdominal metastases in an infant with medulloblastoma: long-term
      remission by systemic chemotherapy and surgery.
AB  - This is the first reported case of long remission of abdominal metastases spread
      through a ventriculo-peritoneal shunt in an infant diagnosed, four years ago, at
      age 1 year and 10 months, to have cerebral medulloblastoma. Two years later,
      while in second complete remission of his cerebral tumor, he showed abdominal
      metastases, successfully treated by platinum based chemotherapy and surgery. One
      year later, a second abdominal relapse and hepatic metastases were treated by
      doxorubicin administration and surgery. Since then the child remained in
      continuous complete remission. This unusual favorable outcome can be explained by
      an extreme responsiveness of the tumor, unprotected by the blood brain barrier,
      to systemic chemotherapy, particularly to doxorubicin administration. The need
      for careful surveillance of patients with ventriculo-peritoneal shunts is
      emphasized. Searching for new tools, such as entrapment of doxorubicin in
      liposomes, able to overcome the blood-brain barrier and to expose brain tumors to
      effective drugs, probably represents the best choice for future treatment
      strategies of CNS tumors.

PMID- 11519857
TI  - TP53 gene mutations, nuclear p53 accumulation, expression of Waf/p21, Bcl-2, and
      CD95 (APO-1/Fas) proteins are not prognostic factors in de novo glioblastoma
      multiforme.
AB  - Glioblastoma multiforme (WHO grade IV; GBM) is the most common primary brain
      tumor with a median survival of less than one year despite multimodal treatment
      regimens. However, a small subgroup of GBM patients has a better clinical
      outcome, with a small number of patients surviving several years. Apoptosis, a
      genetically determined program of cell suicide, may be induced as a consequence
      of critical DNA damage. However, due to defects in the signaling pathways, cancer
      cells may escape apoptosis, despite carrying irreversible DNA damage. In the
      present study, we have analyzed tumors of two age-matched, equally treated groups
      of GBM patients with different postoperative time to tumor progression (TTP),
      defined as 'short-term' for TTP of less than 6 months (n = 54), and 'long-term'
      for TTP of more than 12 months (n = 39) for alterations in apoptosis regulatory
      pathways: Mutations of the TP53 tumor suppressor gene and/or nuclear accumulation
      of its gene product p53, expression of Waf/p21, CD95 (Apo1/Fas), and Bcl-2. TP53
      mutations were found in 12 out of 54 (22%) GBMs of short-term survivors and 8 out
      of 35 (23%) tumors of long-term survivors; the respective numbers for nuclear p53
      protein accumulation were 12/53 (23%) and 10/37 (27%). Waf1/p21 expression was
      found in 13/53 (25%) tumors of short-term survivors and 9/35 (26%) GBMs of long
      term survivors. The respective numbers for Bcl-2 expression were 25/42 (60%) and
      22/36 (61%) and for CD95 (Apo1/Fas) expression 20/49 (41%) and 14/36 (39%) GBMs.
      The percentage of alterations in genes/proteins involved in the apoptotic pathway
      investigated here was virtually identical in the two groups of clinically
      different GBM patients. Thus, our data imply that none of these alterations
      investigated per se has a strong impact on the overall survival of GBM patients.

PMID- 11519859
TI  - High-dose estrogen treatment in postmenopausal breast cancer patients heavily
      exposed to endocrine therapy.
AB  - Estrogens administered in high doses were commonly used for therapy of advanced
      breast cancer before the introduction of contemporary endocrine therapy. While
      the mechanism of the antitumor effect is unknown, in vitro investigations have
      shown estrogens in high concentrations to be toxic to cell growth. Further, it
      has been shown that exposure of MCF-7 cells to estrogens in low concentrations
      may enhance the sensitivity and also lower the toxicity threshold to estrogens.
      This study was designed to evaluate treatment with diethylstilbestrol (DES) in
      postmenopausal women with advanced breast cancer becoming resistant to estrogen
      deprivation. Thirty-two patients with advanced breast cancer previously exposed
      to multiple endocrine treatment regimens (median 4, range 2-10) were enrolled.
      Their tumor should have revealed evidence of endocrine sensitivity (previous
      partial response or at least stable disease for > or = 6 months to therapy). Each
      patient received DES 5 mg t.i.d. Four patients terminated therapy after < or = 2
      weeks on therapy due to side effects; another two patients terminated therapy
      before progression for similar reasons (one patient after SD for 15 weeks and one
      with a PR after 39 weeks). Four patients obtained CR and six patients PR. In
      addition, two patients had SD for > or = 6 months duration. Five patients had an
      objective response and one patient a SD lasting for > or = 1 year. Our results
      reveal estrogens administered in high doses may have antitumor effects in breast
      cancer patients heavily pretreated with endocrine therapy. Such treatment
      represents a valuable alternative to chemotherapy in selected patients.

PMID- 11519860
TI  - The effect of age and density of the breast on the sensitivity of breast cancer
      diagnostic by mammography and ultasonography.
AB  - PURPOSE: We studied which, age of the patient or density of the breast accounts
      for the sensitivity of mammography and ultrasonography (US). Furthermore we
      studied whether the overall impression on the density of the breast or the
      density in tumour area accounts for the sensitivity of mammography and
      ultrasonography. MATERIALS AND METHODS: The material consisted of 572 consecutive
      histologically and 5 cytologically verified breast cancer cases. Mammography and
      US examinations were performed immediately before breast cancer operations and
      information on the findings were received from the original patient files and
      classified as malignant or benign. The density of breast parenchyma to fatty,
      mixed or dense in total breast and separately in tumour area was defined by a
      radiologist group from the original mammograms by comparing to model mammograms.
      The sensitivity (Se) of mammography and US was compared in 3 age groups (26-49,
      50-59 and 60-92) and in the different density classes. RESULTS: Sensitivity of
      mammography increased by age (density-adjusted OR = 0.2, 95%, CI 0.1-0.5) in age
      group 26-49 compared to age group 60-92) and with fattiness of the breast (age
      adjusted OR= 0.4, 95%, CI 0.1-1.0 for dense breast parenchyma in tumour area
      compared to fatty breast). Sensitivity of US was inversely related to age
      (density-adjusted OR = 2.3, 95%, CI 1.0-5.2 in age group 26-49 compared to age
      group 60-92) and directly related with fattiness of breast (age-adjusted OR =
      0.5, 95%, CI 0.2-0.9 by dense breast parenchyma in tumour area compared to fatty
      breast). Density in the tumour area compared to total breast density was related
      only mariginally better sensitivity both of mammography (0.4 vs. 0.6) and of US
      (0.5 vs. 0.6). CONCLUSION: Sensitivity of both mammography and sensitivity of US
      are independently related both to the age of the patient and to the density of
      the breast. The effect of age is inverse and that of density parallel between
      mammography and US on sensitivity. The effect of overall breast density was close
      to the effect of density at the site of the tumour on the sensitivity of both
      mammography and US.

PMID- 11519861
TI  - Impact of the axillary nodal status on sentinel node mapping in breast cancer and
      its relevance for technical proceeding.
AB  - OBJECTIVE: The aim of this study is to analyze whether the axillary status
      influences the lymphatic mapping procedure in malignant breast disease and
      whether clinically relevant consequences for the technique of Sentinel Node (SN)
      biopsy may be drawn from this information. MATERIALS AND METHODS: SN biopsy was
      performed in 150 consecutive patients using a combination of the radioguided and
      the blue-dye technique. Axillary status was compared with the number of detected
      nodes. In cases of numerous nodes with tracer uptake, the radioactivity of each
      radiolabeled node was measured separately in a dose calibrator. We analyzed
      whether an increased tracer uptake could possibly indicate a 'true' or 'dominant'
      SN. Blue dye uptake was registered and compared with radioactivity. The findings
      were related to the histologic results. RESULTS: In patients with a positive
      axillary status, significantly more radiolabeled nodes were detected than in node
      negative patients (median 3 vs. 2; p < 0.001). In 54/86 patients with numerous
      SNs a 'dominant' node with at least twice the radioactivity than other marked
      nodes could be identified (62.8%). From 26 cases with axillary involvement, 20
      patients (76.9%) were identified by the 'dominant' and the remaining six women
      (23.1%) by others than the seemingly leading SN. CONCLUSION: Axillary lymph node
      involvement influences the drainage pattern in breast cancer. Patients with
      numerous SNs have an increased risk of axillary involvement. A high tracer uptake
      does not permit the identification of a 'true' SN. A lack of surgical accuracy
      may lead to pitfalls if the axilla is not screened carefully for all radioactive
      nodes.

PMID- 11519862
TI  - Suppression of aromatase (estrogen synthetase) by red wine phytochemicals.
AB  - Estrogen promotes the proliferation of breast cancer cells. Aromatase is the
      enzyme that converts androgen to estrogen. In tumors, the expression of aromatase
      is upregulated compared to surrounding non-cancerous tissue. In this study, we
      found that wine contains phytochemicals that are capable of suppressing
      aromatase. Red wine was shown to be much more effective than white wine in the
      suppression of aromatase activity. Whole wine, lyophilized wine, and heat-treated
      extracts were examined for aromatase inhibition in a human placenta microsomal
      assay. C18 Sep-Pak cartridge (Waters Co.) separation of red wine extracts under
      an increasing acetonitrile (ACN) gradient found that the most active components
      were in the 20% ACN fraction, in that they inhibited the wild-type human placenta
      aromatase, wild-type porcine placenta and blastocyst aromatase in a dose
      dependent fashion. The 20% ACN active fraction was heat stable and inhibited
      aromatase in a non-competitive manner. The aromatase-inhibitory action of red
      wine extracts was also examined with a transgenic mouse model in which aromatase
      is over-expressed in the mammary tissues. It was found that the intake of the 20%
      ACN fraction by gavage completely abrogated aromatase-induced hyperplasia and
      other changes in the mammary tissue. This is the first report demonstrating that
      wine, especially red wine, contains phytochemicals that can inhibit aromatase.

PMID- 11519863
TI  - Immunohistochemical detection of ornithine-decarboxylase in primary and
      metastatic human breast cancer specimens.
AB  - Increased ornithine decarboxylase (ODC) activity in human breast cancer specimens
      has recently been shown to be an independent adverse prognostic factor for
      recurrence and death. Biochemical measurement of ODC, however, is not practical
      for routine clinical use. Furthermore, it does not take into account the
      heterogeneous composition of human breast cancers which contain variable
      proportions of epithelial and stromal elements. Therefore, we developed an
      immunohistochemical method for ODC determination which can be applied to formalin
      fixed, paraffin-embedded tissue sections. We report here our results in a series
      of 30 human breast cancer samples. ODC expression was detected most consistently
      in the malignant epithelial component of the tumors. Twenty-seven of 30 samples
      stained positive with intensities ranging from 1+ to 3+. The fraction of
      malignant epithelial cells expressing ODC varied among specimens between 10% and
      > 90%. When quantitated by H-SCORE, ODC expression was significantly higher in
      the malignant epithelial component than in normal appearing epithelial cells and
      stroma admixed within the tumor. Normal mammary tissue adjacent to the cancer was
      available for analysis in six cases. ODC expression was absent in two (while both
      cancers were positive) but present in four to a degree which was overall
      comparable to that observed in the corresponding tumors. We believe that this
      technique will be useful for future studies aimed at expanding our knowledge of
      the role of ODC and polyamines (PA) in breast cancer biology.

PMID- 11519864
TI  - 1,25-dihydroxyvitamin D3 and retonic acid analogues induce differentiation in
      breast cancer cells with function- and cell-specific additive effects.
AB  - Vitamin D3 derivatives and retinoids can induce cell cycle arrest,
      differentiation and cell death in many cell lines. These compounds can act
      cooperatively in some of their functions and may be of potential use either
      individually or in combination in the treatment of breast cancer. The effects of
      1,25-dihydroxyvitamin D3 (1,25(OH)2D3), all-trans retinoic acid (ATRA) and
      several analogues were evaluated on malignant phenotypic traits of breast cancer
      cell lines MCF-7, T-47D and MDA-MB-231. Both 1,25(OH)2D3 and ATRA caused a
      decrease in anchorage independent colony formation in MCF-7 and T-47D cells in a
      dose-dependent manner. The effects of 1,25(OH)2D3 10(-10) and 10(-9) M were
      synergistic with ATRA 10(-8) M in T-47D cells but were antagonistic in both MCF-7
      and in T-47D cells at most concentrations. Both 1,25(OH)2D3 and ATRA individually
      induced an accumulation of MCF-7 cells in the G1 phase of the cell cycle and an
      associated increase in p21WAFI/CiP1, p27KiP1 and a dephosphorylation of Rb but
      the effects were not additive. Both compounds inhibited the invasive capacity of
      MDA-MB-231 cells. 1,25(OH)2D3 but not ATRA caused an increase in E-cadherin
      levels in MDA-MB-231 cells. These two functions were not additive. The compounds
      1,25(OH)2D3, a noncalcemic analogue 1,25(OH)2-16-ene-23-yne-D3, ATRA, AGN195183,
      an RARalpha-specific agonist, and AGN190168 (tazarotene), an RARbeta/gamma
      selective agonist, induced differentiation as determined by measurements of lipid
      droplet formation. The individual effects of 1,25(OH)2-16-ene-23-yne-D3 combined
      with ATRA or with tazarotene at 10(-9) M each were additive in MCF-7 and MDA-MB
      231 cells on lipid formation. The data demonstrate that both 1,25(OH)2D3, ATRA,
      and selected analogues induce a more differentiated phenotype in breast cancer
      cells with additive effects that are function- and cell-specific.

PMID- 11519865
TI  - Bone marrow micrometastases detected by RT-PCR for mammaglobin can be an
      alternative prognostic factor of breast cancer.
AB  - PURPOSE: To evaluate a new prognostic factor of breast cancer, bone marrow
      micrometastases which was detected by RT-PCR for mammaglobin, a sensitive
      molecular marker of breast cancer, was examined. MATERIALS AND METHODS: One
      hundred and eleven samples from stage I-III breast cancer patients were examined.
      Bone marrow micrometastases and clinicopathological parameters, which were age,
      tumor size, lymph node metastasis and status of the estrogen receptor, were
      evaluated for the prognostic factor by statistical analysis. RESULTS: Median
      follow-up time was 21.1 months. Thirty-three (29.7%) out of 111 samples were RT
      PCR positive. Eight cases (24.2%) in this group showed recurrent lesions in the
      distant organs. Whereas six (7.7%) out of 78 RT-PCR negative patients had distant
      recurrences. In the premenoposal patients, and in the patients with axillary
      lymph node metastases, RT-PCR positive cases showed significantly higher distant
      recurrent rate. Bone marrow micrometastases, axillary nodal status, and estrogen
      receptor were independent prognostic factors for breast cancer by both univariate
      and multivariate analysis. CONCLUSIONS: Bone marrow micrometastases detected by
      RT-PCR for mammaglobin can be a useful predictive marker for early distant
      recurrence of breast cancer.

PMID- 11519866
TI  - Mammographic finding as predictor of survival in 1-9 mm invasive breast cancers.
      worse prognosis for cases presenting as calcifications alone.
AB  - PURPOSE: To investigate breast cancer survival in small invasive breast cancers
      in relation to mammographic findings. MATERIALS AND METHODS: We investigated a
      consecutive series of 96 cases of 1-9mm small invasive breast cancers diagnosed
      1988-1994. Median follow-up of the survivors was 7 years (range: 4.5-10.5).
      Mammographic findings were classified into rounded masses, spiculated masses,
      calcifications (casting or pleomorphic) and masses combined with calcifications.
      Lymph node status and histological malignancy grade were also evaluated. Eight
      year survival rate in breast cancer was estimated with the Kaplan-Meier method
      and risk of death with proportional-hazards regression. RESULTS: 6/96 women died
      from breast cancer. 3/14 had calcifications alone, 2/56 with spiculated masses,
      1/12 with rounded masses. 5/78 who died were node-negative cancers and 1/4 was
      node-positive. The survival rate for the whole group was 93%: 77% for the
      calcifications alone group, 95% for spiculated masses and 91% for rounded masses.
      The survival rate for the node-negative cancers was 92% compared to 75% for node
      positive cancers. Calcifications alone (p = 0.01) and node positivity (p =0.03)
      had each independent significant higher risk of death taking finding, node status
      and grade into account. CONCLUSION: Small invasive breast cancers
      mammographically presenting as casting or pleomorphic calcifications alone have a
      significantly worse prognosis than other types.

PMID- 11519867
TI  - Mammography utilization among california women age 40-49 in a managed care
      environment.
AB  - OBJECTIVE: To examine the utilization of screening mammography and the
      relationship between risk factors and mammography use in women age 40-49 in a
      managed care environment. DESIGN: Retrospective observational study based on a
      mailed survey. SETTING: A large HMO in California. PATIENTS/PARTICIPANTS: The
      study population included respondents age 40-49 who completed a breast health
      assessment questionnaire mailed to all women age 34-49 and enrolled in a
      California HMO in early 1997. MAIN RESULTS: About 67.6% of the 20,391 women age
      40-49 had at least one mammogram during 1995 and 1996. Logistic regression
      revealed that women age 40-44 were less likely (odds ratio: 0.83-0.90) than women
      age 45-49 to obtain mammography. Family history of breast cancer (odds ratio:
      1.12-1.16), breast biopsy (odds ratio: 1.14-1.18), and a mammogram in the
      previous three years (odds ratio: 1.15-1.18) were associated with an increased
      likelihood of taking a mammogram. However, monthly breast self-exams (odds ratio:
      0.996-1.04), having a child at or after age 30 (odds ratio: 0.97-1.02), and
      having menarche at age 12 or younger (odds ratio: 0.96-1.01) had no significant
      effect on the screening mammography rates. CONCLUSION: A relatively higher
      percentage of younger HMO members receive screening mammography than that of
      general population. However, some higher-risk groups, especially women whose
      first pregnancies were late in life, do not show a higher rate of using
      mammography.

PMID- 11519868
TI  - BRCA1 and BRCA2: to test or not to test.

PMID- 11519869
TI  - Pathobiologic identification of two distinct breast carcinoma subsets with
      diverging clinical behaviors.

PMID- 11519870
TI  - Characterization of bipotent mammary epithelial progenitor cells in normal adult
      human breast tissue.
AB  - The purpose of the present study was to characterize primitive epithelial
      progenitor populations present in adult normal human mammary tissue using a
      combination of flow cytometry and in vitro colony assay procedures. Three types
      of human breast epithelial cell (HBEC) progenitors were identified: luminal
      restricted, myoepithelial-restricted and bipotent progenitors. The first type
      expressed epithelial cell adhesion molecule (EpCAM), alpha6 integrin and MUC1 and
      generated colonies composed exclusively of cells positive for the luminal
      associated markers keratin 8/18, keratin 19, EpCAM and MUC1. Bipotent progenitors
      produced colonies containing a central core of cells expressing luminal markers
      surrounded by keratin 14+ myoepithelial-like cells. Single cell cultures
      confirmed the bipotentiality of these progenitors. Their high expression of
      alpha6 integrin and low expression of MUC1 suggests a basal position of these
      cells in the mammary epithelium in vivo. Serial passage in vitro of an enriched
      population of bipotent progenitors demonstrated that only myoepithelial
      restricted progenitors could be readily generated under the culture conditions
      used. These results support a hierarchical branching model of HBEC progenitor
      differentiation from a primitive uncommitted cell to luminal- and myoepithelial
      restricted progenitors.

PMID- 11519871
TI  - Comparative cytogenetics among allopatric populations of the fish, Hoplias
      malabaricus. Cytotypes with 2n = 42 chromosomes.
AB  - The available chromosomal data on Hoplias malabaricus make possible the
      identification of three major karyotypic forms in this fish group, all of them
      bearing 2n = 42 chromosomes, and named as Cytotypes A, B and E in previous
      studies. While Cytotype A and B share a general macrokaryotypic feature, Cytotype
      E is well differentiated concerning the morphology and size of some chromosome
      pairs. On the other hand, Cytotype B presents an exclusive XX/XY sex chromosome
      system. Six allopatric populations, belonging to Cytotype A, were subjected to
      cytogenetic analysis in the present study. Despite their basic karyotypic
      similarity, some differences in the chromosome formulae, as well as in the
      heterochromatin and Ag-NORs locations, were observed among populations indicating
      that they no more correspond to a unit, at least in the cytogenetical level.

PMID- 11519872
TI  - Age-specific effects of novel mutations in Drosophila melanogaster I. Mortality.
AB  - Theories for the evolution of aging rest on the assumption that at least some
      deleterious mutations have effects that are limited to certain ages. Many
      mutation accumulation studies have tried to measure the number and magnitude of
      deleterious mutations, but few studies have tried to determine the extent to
      which the effects of mutations are limited to particular ages. Here we estimate
      the age-specific effect of deleterious mutations on mortality rate in an outbred
      population of the fruit fly, Drosophila melanogaster. We used the 'middle class
      neighborhood' approach to accumulation mutations in populations of flies that had
      recently been obtained from the wild. There are mutations that increase mortality
      rates, but whose effects are limited to specific ages. The age-specificity of
      mutational effects differs between the sexes, between virgin and mated flies, and
      over time. After 10 and 20 generations of mutation accumulation, there were clear
      age-specific effects of mutations. After 30 generations, however, the degree of
      age-specificity decreased. In addition, mutation accumulation led to a steady
      increase in larval mortality and a small but significant increase in the sex
      ratio of eclosing flies. We discuss the implications of these results for models
      of aging, and suggest approaches that future studies should take to obtain
      accurate information on the age-specificity of novel mutations.

PMID- 11519873
TI  - Age-specific effects of novel mutations in Drosophila melanogaster II. Fecundity
      and male mating ability.
AB  - Evolutionary theories of senescence assume that mutations with age-specific
      effects exist, yet until now, there has been little experimental evidence to
      support this assumption. In this study, we allowed mutations to accumulate in an
      outbred, wild population of Drosophila melanogaster to test for age-specific
      differences in both male mating ability and fecundity. We assayed for age
      specific effects of mutations after 10, 20, and 30 generations of mutation
      accumulation. For mating ability, we found the strongest effects of mutations in
      the first half of the life span after 20 generations, and at nearly all ages by
      generation 30. These results are qualitatively consistent with results from a
      companion study in which age-specific mortality was assayed on the same lines of
      D. melanogaster. By contrast, effects of fecundity were confined to late ages
      after 20 generations of mutation accumulation, but by generation 30, as with male
      mating ability, effects of novel mutations were distributed across all age
      classes. We discuss several possible explanations for the differences that we
      observe between generations within traits, and among traits, and the relevance
      for these patterns to models of aging as well as models of mate choice and sexual
      selection.

PMID- 11519874
TI  - Diversity in the integrase coding domain of a gypsy-like retrotransposon among
      wild relatives of rice in the Oryza officinalis complex.
AB  - The Oryza officinalis complex is a genetically diverse, tertiary genepool of
      rice. We analyzed part of the primary structure of the integrase coding domain
      (ICD) of a gypsy-like retrotransposon from species of the O. officinalis species
      complex. PCR was performed with degenerate primers that hybridized to conserved
      sequences in the integrase genes of gypsy-type retrotransposons, using total DNA
      from different species of the O. officinalis complex as templates. Cloning and
      sequencing of the PCR products showed that the amplified fragments are highly
      homologous to each other (75-90%) and belong to one family of retrotransposons
      that is related to the previously studied RIRE-2 element from rice. Two main
      subfamilies of 292 and 351 bp were distinguished. Analysis of primary sequence
      data supports previous reports that sequence divergence during vertical
      transmission has been the major influence on the evolution of gypsy-type
      retrotransposons in Oryza species. Based on sequence data phylogenetic
      relationships among species of the O. officinalis complex were estimated. The
      data suggests that O. eichingeri is more closely related to the ancestral species
      of the complex.

PMID- 11519875
TI  - Nucleolar organizing regions, 18S and 5S rDNA in Astyanax scabripinnis (Pisces,
      Characidae): populations distribution and functional diversity.
AB  - Astyanax scabripinnis specimens from four distinct populations in Brazil were
      studied with respect to their karyotype macrostructure, nucleolar organizer
      regions, and 18S and 5S rRNA genes. The four populations showed a 2n = 50
      chromosomes (3 M + 11 SM + 5 ST + 6 A pairs) and 1-2 B chromosomes. No
      chromosomal differentiations were observed between sexes. Although a karyotypic
      diversity has been characterized in this fish group, the populations now analyzed
      presented the same macrokaryotypic pattern. Chromosome mapping of 5S rDNA showed
      a total of eight sites located in four distinct chromosomal pairs, with no
      apparent differences among populations. A comparative study on 18S rDNA locations
      and Ag-NORs showed some secondary NOR sites that are not usually expressed in
      karyotypes and a probable differential NOR activity among populations.
      Correlations between these data, environmental conditions and B chromosomes are
      discussed.

PMID- 11519876
TI  - A reciprocal relationship between the genetic diversity at two metabolically
      linked isozyme loci in several conifer species.
AB  - In the context of a general survey on genetic variation of isozyme-gene systems
      which function in the carbohydrate degradation and conversion, we detected a
      reciprocal relationship between genetic diversity at the hexokinase (HEK-A) and
      phosphoglucose isomerase (PGI-B) loci in Scots pine populations. Further studies
      on Norway spruce, Douglas-fir and Siberian stone pine revealed that this
      relationship appears to be a more general phenomenon in conifers such that
      increasing diversity at one locus is correlated with a decrease in diversity at
      the other locus. Since the two gene loci are not structurally linked but are
      encoding enzymes of two sucessive metabolic steps in the glucose conversion
      towards glycolysis, it is assumed that some sort of selection, especially during
      germination and early embryo development, may be the causal explanation. A
      metabolically-based model incorporating selective advantage and disadvantage of
      alternate two-locus genotypes at HEK-A/PGI-B was presented in order to elucidate
      the possible adaptive nature of this reciprocal relationship.

PMID- 11519877
TI  - Molecular and cytogenetic analysis of the goby Gobius niger (Teleostei,
      Gobiidae).
AB  - A molecular cytogenetic study of Gobius niger has been conducted by treating its
      mitotic chromosomes with silver-, CMA3- and DAPI-staining and fluorescent in situ
      hybridization using four multicopy or repetitive DNAs (the 28S and 5S rDNAs, the
      TTAGGG telomeric repeat and the mariner-like elements) as probes. In particular,
      the study proved the presence of NOR heteromorphism and suggested the possible
      role of the transposable element mariner in its genesis. In situ hybridization
      with the 5S rDNA probe proved the presence of just one 5S-bringing chromosome
      pair, whereas hybridization with the telomeric repeat revealed small bright
      hybridization spots, uniform in size and intensity, on each telomere of all
      chromosomes but no interstitial signals were noticed.

PMID- 11519878
TI  - High stressful temperature and genetic variation of five quantitative traits in
      Drosophila melanogaster.
AB  - Variation of five quantitative traits (thorax length, wing length, sternopleural
      bristle number, developmental time and larva-to-adult viability) was studied in
      Drosophila melanogaster reared at standard (25 degrees C) and high stressful (32
      degrees C) temperatures using half-sib analysis. In all traits, both phenotypic
      and environmental variances increased at 32 degrees C. For genetic variances,
      only two statistically significant differences between temperature treatments
      were found: the among-sire variance of viability and the among-dam variance of
      developmental time were higher under stress. Among-sire genetic variances and
      evolvabilities were generally higher at 32 degrees C but narrow sense
      heritabilities were not. The results of the present work considered in the
      context of other studies in D. melanogaster indicate different patterns of
      genetic variation between stressful and nonstressful environments for the traits
      examined. Data on thorax length and viability agree with the hypothesis that
      genetic variance can be increased under extreme environmental conditions.

PMID- 11519879
TI  - Occurrence of double strand DNA breaks and pairing of homologous chromosomes are
      preconditions of crossing over in Drosophila melanogaster, and its timing.
AB  - Brood pattern analysis of the effect of a heat shock (35 degrees C 24h) given to
      the parental females in presence and absence of In (2L + 2R) Cy in heterozygous
      condition in the second chromosome on recombination and interference in the cv-v
      f region of the X chromosome showed the following: (i) In the absence of the
      inversion recombination frequencies in both gene intervals increased in the daily
      broods, which represent oocytes in which premeiotic DNA synthesis was occurring
      during the heat shock treatment. (ii) In the presence of the inversion
      recombination frequencies did not increase in any of the daily broods. (iii) The
      frequencies of double crossovers did not increase in any broods either in the
      presence or in the absence of inversion. (iv) The coefficient of coincidence
      changed in virtually all broods both in the presence and absence of the
      inversion, indicating that the heat shock affects the distribution of single
      crossovers. (v) The results showed that the effect of the heat shock on the
      coefficient of coincidence was similar during premeiotic DNA synthesis both in
      the absence and presence of the inversion, but different in the broods
      representing oocytes which were undergoing the first meiotic division, suggesting
      that crossing over occurs during this division, probably during pachytene.

PMID- 11519880
TI  - Analyses of nucleolus organizer regions and heterochromatin of Pimelodus
      maculatus (Pisces, Pimelodidae).
AB  - Eighteen specimens of Pimelodus maculatus collected from Tibagi River (Sertaneja,
      PR, Brazil) were analyzed cytogenetically. The diploid number of 56 chromosomes
      was observed and karyotype was 20 M + 20 SM + 10 ST + 6 A with fundamental number
      (FN) of 106. Results of analyses from the nucleolus organizer regions (NORs),
      obtained by AgNO3, CMA3 and C-band staining showed marking in a terminal position
      on the long arm of a pair of subtelocentric chromosomes. The restriction enzyme
      AluI produced a linear differentiation similar to C-banding.

PMID- 11519881
TI  - Effect of a pharmacological activation of PPAR on the expression of RAR and TR in
      rat liver.
AB  - It has recently been shown that high-fat diets induce the expression of
      peroxisome proliferator-activated receptor (PPAR) with a concomitant decrease in
      expression of retinoic acid (RAR) and triiodothyronine (TR) receptors in rat
      liver. The authors have suggested that PPAR activation may be responsible for
      these modifications in nuclear receptor expression. With the aim of gaining
      further insight into a possible relationship between the patterns of expression
      of these receptors, we have examined, using a pharmacological model, the effect
      of a strong and specific PPAR activation induced by bezafibrate, a peroxisome
      proliferator agent. Activation of PPAR was evaluated by quantifying PPAR alpha
      mRNA and acyl-CoA oxidase mRNA. The expression of RAR and TR was determined by
      assaying the binding properties of these nuclear receptors and by quantifying the
      mRNA level of RAR beta and TR alpha1,beta1 isoforms. After a 10 day treatment of
      young rats, induction of PPAR (PPAR alpha mRNA was increased by 40% [P< 0.05 and
      acyl-CoA oxidase mRNA by 411% [P<0.001]) and a concomitant decrease of RAR and TR
      expression (Maximal Binding Capacity was decreased by 21 and 26%, respectively
      [P<0.05]) in the liver was observed. RXR alpha mRNA expression was unchanged by
      treatment. Cross-talk between RAR, TR and PPAR signalling pathways may be
      implicated in the new patterns of nuclear receptor expression observed. The
      decreased expression of RAR and TR reported here could provide a novel element
      for the understanding of the link between PPAR and tumorigenesis in rat liver.

PMID- 11519882
TI  - Influence of epidermal growth factor on mammalian oocyte maturation via tyrosine
      kinase pathway.
AB  - Epidermal growth factor (EGF) has been reported to promote different functions in
      mammalian ovaries, including oocyte maturation. The aim of the present study was
      to establish: that EGF influences oocyte maturation in ovine and equine, that a
      tyrosine kinase-dependent intracellular mechanism mediates EGF effect and, that
      EGF-R receptor is detectable in ovarian follicles by immunohistochemistry
      methods. Selected ovine and equine oocytes were aspirated from 2-5 mm (ovine) or
      25 mm (equine) follicles and cultured in TCM 199 for 22 (ovine) or 36 hours
      (equine). They are then subjected to culture with EGF and two specific tyrosine
      kinase inhibitors (TKIs, tyrphostins A-23 y A-47). Maturation was determined as
      the percentage of oocytes at metaphase II stage after culture. Treatments with
      EGF significantly increased incidences of metaphase II stage compared to controls
      (86.2% vs. 55% and 70.4% vs. 22.5% in ovine and equine oocytes, respectively).
      Tyrphostins A-23 and A-47 were effective in suppressing EGF-effect on oocytes.
      EGF-receptor was localized in follicles, being more prominent in cumulus and
      granulosa cells. These results confirm that EGF has a physiological role in the
      regulation of oocyte maturation via tyrosine-kinase pathway.

PMID- 11519883
TI  - Endocrine profiles during doe-litter separation and the subsequent pregnancy in
      rabbits.
AB  - This study was carried out to determine the effects of a transient doe-litter
      separation on plasma prolactin, LH, FSH, estradiol-17beta and progesterone
      concentrations before artificial insemination and during the subsequent
      pregnancy. Control does (n=12) had free access to nursing, whereas separated does
      (n=12) were kept away from their litters for 48 hours before artificial
      insemination. Both groups were inseminated on day 11 after parturition. Teat
      stimulation by suckling caused a high increase in prolactin concentrations in
      separated does (p < 0.0001). Basal prolactin concentrations were observed in both
      groups on days 8 and 18 of pregnancy. No effect of the treatment was detected on
      LH and FSH concentrations during the sampling period. A rise of estradiol-17beta
      concentrations was observed 48 hours after doe-litter separation, compared to
      control does and to previous values (p < 0.003). Both groups showed low
      progesterone concentrations before artificial insemination. Pregnant rabbits in
      both groups showed increased progesterone concentrations on days 8 and 18 of
      pregnancy. Lower estradiol-17beta concentrations were observed in control does on
      day 18 of pregnancy compared with separated rabbits (p < 0.003). The results
      suggest that a transient separation of nursing does from their litters before
      artificial insemination may promote high follicular steroidogenesis activity
      leading to increased estradiol-17beta concentrations. This hormonal change could
      be a result of several stimulatory actions probably triggered by the absence of
      suckling episodes and may affect the luteotrophic function during the subsequent
      pregnancy.

PMID- 11519884
TI  - Characterization of a new plasma membrane-associated ecto-5'
      phosphodiesterase/nucleotide-pyrophosphatase from rat hepatocarcinoma AS-30D
      cells.
AB  - We have identified in plasma membrane fractions isolated from rat hepatocarcinoma
      AS-30D ascites cells three glycoproteins of 125 kDa, 115 kDa and 105 kDa (gp125,
      gp115 and gp105) which become adenylylated using ATP as substrate, most readily
      in the presence of EDTA. The gp115 becomes also phosphorylated. The adenylylation
      of these tumor glycoproteins was much lower than that of a group of analogous
      adenylylatable glycoproteins (gp130, gp120-gp110 dimer and gp100) present in
      normal rat liver plasma membrane. The tumor glycoproteins were reversibly O
      adenylylated at threonine residues, as was the case for their normal rat liver
      counterparts. The tumor gp115, and the gp120-gp110 dimer from normal rat liver
      were both isolated using either ATP-affinity chromatography and/or AMP-affinity
      chromatography. The gp120-gp110 dimer from normal rat liver was identified as the
      plasma cell differentiation antigen-1 (PC-1 protein), an ecto-5'
      phosphodiesterase/nucleotide-pyrophosphatase (5'-PDE/NPPase). The gp115 from
      tumor cells also exhibited Zn2+ stimulated 5'-PDE and NPPase activities in
      alkaline conditions, although it appears to be distinct from the PC-1 protein. We
      have determined that the gp115 is an ecto-enzyme that catalyzes the hydrolysis of
      extracellular ATP, since its adenylylation and phosphorylation were detected in
      intact cells using extracellularly added [alpha-32P]ATP or [gamma-32P]ATP,
      respectively, in the absence of any permeabilizing agent.

PMID- 11519886
TI  - IGF-I does not improve fat malabsorption in cirrhotic rats.

PMID- 11519887
TI  - Physical exercise intensity can be related to plasma glutathione levels.
AB  - The aim of the present study was to examine the effect of different kinds of
      physical exercise on plasma glutathione levels. Male Wistar rats were randomly
      divided into four groups: In walking group (W; n=6), rats were trained to walk
      0.8 m/min for 45 min; slow running group (SR; n=6) were trained to run 4 m/min
      for 45 min; fast running group (FR; n=6) ran 8 m/min for 60 min and control rats
      (C; n=6) remained in their home cages. All animals were sacrificed after exercise
      and the levels of reduced glutathione (GSH) in plasma samples determined by high
      performance liquid chromatography (HPLC) with a fluorescent detector. Compared to
      controls, exercise did not change GSH plasma levels of the W group. A tendency to
      decrease blood GSH was observed in plasma samples of the SR group and in the FR
      group, physical exercise resulted in a dramatic decrease in GSH plasma levels.
      These data suggest that during light physical exercise there is a low production
      of reactive oxygen species (ROS) with a low request for antioxidant defence such
      as oxidation of GSH. The dramatic decrease observed in GSH levels in FR rats
      would indicate the presence of oxidative stress able to modify blood antioxidant
      profiles. Our results suggest that GSH plays a central antioxidant role in blood
      during intensive physical exercise and that its modifications are closely related
      to exercise intensity.

PMID- 11519885
TI  - Vitamin E: action, metabolism and perspectives.
AB  - Natural vitamin E includes four tocopherols and four tocotrienols. RRR-alpha
      tocopherol is the most abundant form in nature and has the highest biological
      activity. Although vitamin E is the main lipid-soluble antioxidant in the body,
      not all its properties can be assigned to this action. As antioxidant, vitamin E
      acts in cell membranes where prevents the propagation of free radical reactions,
      although it has been also shown to have pro-oxidant activity. Non-radical
      oxidation products are formed by the reaction between alpha-tocopheryl radical
      and other free radicals, which are conjugated to glucuronic acid and excreted
      through the bile or urine. Vitamin E is transported in plasma lipoproteins. After
      its intestinal absorption vitamin E is packaged into chylomicrons, which along
      the lymphatic pathway are secreted into the systemic circulation. By the action
      of lipoprotein lipase (LPL), part of the tocopherols transported in chylomicrons
      are taken up by extrahepatic tissues, and the remnant chylomicrons transport the
      remaining tocopherols to the liver. Here, by the action of the "alpha-tocopherol
      transfer protein", a major proportion of alpha-tocopherol is incorporated into
      nascent very low density lipoproteins (VLDL), whereas the excess of alpha
      tocopherol plus the other forms of vitamin E are excreted in bile. Once secreted
      into the circulation, VLDL are converted into IDL and LDL by the action of LPL,
      and the excess of surface components, including alpha-tocopherol, are transferred
      to HDL. Besides the LPL action, the delivery of alpha-tocopherol to tissues takes
      place by the uptake of lipoproteins by different tissues throughout their
      corresponding receptors. Although we have already a substantial information on
      the action, effects and metabolism of vitamin E, there are still several
      questions open. The most intriguing is its interaction with other antioxidants
      that may explain how foods containing small amounts of vitamin E provide greater
      benefits than larger doses of vitamin E alone.

PMID- 11519888
TI  - Reduction of delayed renal allograft function using sequential immunosuppression.
AB  - Previous data suggested that outcome in small children with cadaveric renal
      transplantation might be improved with sequential therapy. This protocol combines
      augmented immunosuppression [by including antibody induction (ATG)] with
      avoidance of nephrotoxic medication in the immediate postoperative phase (by
      delayed start of cyclosporin therapy). In this report, we describe effects of
      this approach in 12 consecutively transplanted small children of less than 5
      years of age (mean 3.2 years) who received a cadaveric renal graft at our
      institution between 1991 and 1998. Up to 1996 triple therapy (prednisolone,
      azathioprine, cyclosporin) and since 1997 sequential therapy (prednisolone,
      azathioprine, ATG until serum creatinine <2 mg/dl, then cyclosporin) was used for
      immunosuppression. Five children had delayed graft function (45.4%), all of whom
      were treated with triple therapy including cyclosporin from the very beginning,
      whereas children treated by the sequential protocol gained immediate graft
      function (P<0.05). There was no statistical difference between the two protocols
      concerning frequency or severity of rejections (67% vs. 60%, all steroid
      responsive), difference in the incidence of either bacterial or viral infections,
      or between the incidence of hypertension. Although not reaching statistical
      significance, 1-year graft survival rates also increased from 60% for triple
      therapy to 80% for sequential therapy. In conclusion, our findings confirm
      previous studies showing that outcome in small children undergoing renal
      transplantation may be improved by specially tailored treatment protocols such as
      sequential therapy.

PMID- 11519889
TI  - Developmental changes in cyclooxygenase mRNA expression in the kidney of rats.
AB  - Prostaglandins, synthesized by cyclooxygenase (COX), regulate renal hemodynamics
      and also epithelial water and solute transport. To determine whether COX mRNA
      expression changes with age, we studied expression in renal medulla and in cortex
      in developing rats at various ages. We also examined age-related changes in COX
      mRNA expression induced by lipopolysaccharide (LPS). COX mRNA was quantitatively
      analyzed in a real-time polymerase chain reaction (PCR) with dual-labeled
      fluorogenic probes. COX-1 mRNA expression did not change with age in cortex or
      medulla. COX-2 mRNA expression was highest in 1-week-old rats and lowest in 4-
      and 8-week-old rats. Lipopolysaccharide treatment did not alter COX-1 mRNA
      expression in infantile or adult rats. In adults, LPS at 1, 5, and 10 mg/kg
      induced COX-2 mRNA expression in renal medulla; the higher doses, 5 and 10 mg/kg,
      induced COX-2 expression in cortex. In infantile rats, COX-2 mRNA, already high
      in the unmanipulated state, was further increased by only 1 mg/kg LPS in both
      renal cortex and medulla. Age-related changes in the expression of COX-2 mRNA
      might be responsible for changing physiologic characteristics of renal function
      during postnatal development in rats, and may be important in renal cortical
      development.

PMID- 11519890
TI  - A family with Jeune syndrome.
AB  - Jeune syndrome is a rare autosomal recessive disease characterized by narrow
      thoracic cage and short-limbed dwarfism. Seventy percent of affected individuals
      die in early childhood from pulmonary hypoplasia and respiratory distress due to
      the small size of the thorax. Growth retardation and chronic renal insufficiency
      due to nephronophthisis may occur in patients who survive the respiratory
      failure. We report a family that exhibited clinically heterogeneous features of
      Jeune syndrome. The 6-year-old male proband presented with skeletal deformities
      and chronic renal failure. A kidney biopsy revealed that nephronophthisis was the
      cause of the patient's kidney failure, and we diagnosed Jeune syndrome. A
      retrospective diagnosis of Jeune syndrome was also established for the proband's
      older sister, who had died of renal failure at 8 years of age. The oldest female
      child in the family also had thoracic deformity, and the father and paternal
      uncle were both of short stature and exhibited brachydactyly. Their renal
      function and blood pressure were normal. The findings in this family are
      important in that they demonstrate the clinical heterogeneity of Jeune syndrome
      and underline the association of renal disease with this syndrome.

PMID- 11519891
TI  - Novel WT1 mutation (C388Y) in a female child with Denys-Drash syndrome.
AB  - We report the identification of a novel Wilms tumor suppressor gene mutation in a
      5-month-old girl who presented with unilateral Wilms tumor (WT) and renal diffuse
      mesangial sclerosis typical of Denys-Drash syndrome (DDS). The patient did not
      have ambiguous genitalia and the karyotype (by amniocentesis) was 46, XX. A de
      novo constitutional heterozygous mutation in WT1 gene exon 9 coding for the third
      zinc-finger (1163G-->A, C388Y) was identified. This mutation affects a cysteine
      residue involved in the coordination of the zinc atom, confirming the importance
      of these residues in the biological function of WT1 protein.

PMID- 11519892
TI  - Growth hormone therapy in chronic renal failure induces catch-up of head
      circumference.
AB  - Growth of head circumference was studied along with height, weight, and body mass
      index (BMI) in 21 prepubertal patients with chronic renal failure (CRF) before
      and during recombinant human growth hormone (rhGH) treatment. CRF was present
      from birth in 15 patients, in the 6 others it was acquired and existing for at
      least 1 year. Five patients were on chronic dialysis, and 16 children were on
      conservative treatment with a median glomerular filtration rate of 17 ml/min per
      1.73 m2 at the start of rhGH therapy. rhGH was administered for 12 months in all
      patients, for 18 months in 19, and for 24 months in 12 patients. Mean height
      standard deviation score (SDS) increased significantly from -2.29 to -1.31 after
      1 year and to -1.07 after 2 years. Mean BMI SDS was within the normal range
      throughout. Mean head circumference SDS improved significantly from -2.04 to 
      1.45 after 1 year and remained stable thereafter. Changes in head circumference
      differed between patients under 5 years and those over 5 years. In the former,
      the increase in head circumference SDS was already significant after 6 months of
      therapy, in the latter, significance was reached only after 1 year. It can be
      concluded that rhGH in CRF patients significantly improves head circumference
      SDS, albeit not to the same extent as height SDS.

PMID- 11519893
TI  - Creatinine excretion rates for renal clearance studies.
AB  - A total of 637 timed-urine collections for creatinine excretion rates obtained
      from 295 children over 14 years have been analyzed. The children ranged in age
      from 2.8 to 21.7 years at the time of the clearance study. The data analyzed
      included only one study from a child during any 6-month period. The objective is
      to provide data defining the expected range of creatinine excretion for renal
      clearance studies. One hundred forty-two studies were conducted on children not
      pretreated with cimetidine and 495 on those pretreated with cimetidine. Analysis
      showed that pretreatment with cimetidine for creatinine clearance studies does
      not alter creatinine excretion rates (P=0.080; 95% CI -0.03 to 1.61). Creatinine
      excretion rates in urine collections obtained at home (roughly 24-h collections)
      were compared with 2-h supervised collections in the Children's Kidney Center.
      The supervised urine collections resulted in creatinine excretion rates 1.38
      mg/kg/24 h greater than home collections (P=0.001; 95% CI 0.76-2.00). Using
      regression equations for creatinine excretion rate with age, tables have been
      prepared showing the expected rate of creatinine excretion for renal clearance
      studies in children 3-21 years of age.

PMID- 11519894
TI  - Changes of renal flow volume in the hemolytic-uremic syndrome--color Doppler
      sonographic investigations.
AB  - Varying degrees of vascular occlusion can be found in the hemolytic-uremic
      syndrome (HUS). This is the rationale for Doppler sonographic investigations of
      renal blood flow in children with HUS. In 1989 a first report suggested a close
      relationship between normalization of the resistive index (RI) of renal blood
      flow with the restitution of urine flow in affected children. Later reports did
      not confirm these initial findings. The aim of this paper is to describe renal
      volume perfusion quantitatively in children with HUS. The renal arteries in 35
      patients with HUS (1 month to 15 years) were investigated at the onset of HUS by
      color Doppler ultrasonography. Flow volume measurements were carried out in the
      1st week and in the 2nd to 4th week after onset of the disease. These data were
      compared with measurements from a healthy pediatric population of 69 children.
      Statistically significant changes in renal perfusion occur in the flow volume of
      the kidneys. The flow volume dropped to 32% (34%) in the 1st week of the disease
      compared with the normal population and recovered in 2-4 weeks to 117% (65%) of
      the normal flow volume (left kidney in parentheses). The new technique of
      volumetric perfusion measurement overcomes some drawbacks of the traditional RI,
      which may have led to some confusion in the past.

PMID- 11519895
TI  - Angiotensin converting enzyme gene polymorphism in primary vesicoureteral reflux.
AB  - We studied the insertion/deletion (I/D) polymorphism of the angiotensin
      converting enzyme (ACE) gene in 78 patients with primary vesicoureteral reflux
      (VUR), and examined renal function by dimercaptosuccinate (DMSA) renoscintigraphy
      and diethylenetriamine-penta-acetic acid (DTPA) renogram in each genotype.
      Patients were classified into three genotypes according to the ACE gene I/D
      polymorphisms: 32 in II genotype, 36 in ID, and 10 in DD. The incidence of
      presumably congenital unilateral small kidneys was high in DD patients (70%).
      Glomerular filtration rate obtained from DTPA renogram was 120.7+/-35.7 ml/min
      (expressed as mean+/-SD) in II genotype, 111.7+/-33.3 in ID, and 88.0+/-18.0 in
      DD. The total quantitative DMSA tracer uptake of both kidneys was also low in
      patients with the D allele. This study shows that the D allele of ACE gene is
      closely related to small congenital kidneys with refluxing ureters in patients
      with primary VUR, and in accordance with previous reports, this allele is also
      related to the progression of reflux nephropathy.

PMID- 11519896
TI  - Galloway-Mowat syndrome: a glomerular basement membrane disorder?
AB  - We report a female infant with Galloway-Mowat syndrome. In addition to the
      characteristic dysmorphic appearance, neurological anomalies and early-onset
      nephrotic syndrome, she had arachnodactyly, an observation thus far reported
      uniquely in Taiwan. Also, her elder sister had the same condition. Renal
      pathology on light microscopy showed cystic dilatation of the renal tubules.
      Electron microscopy showed an irregular glomerular basement membrane and
      effacement of foot processes. This observation suggests that malformation of the
      glomerular basement membrane may cause the glomerulopathy in Galloway-Mowat
      syndrome.

PMID- 11519897
TI  - Primary focal segmental glomerulosclerosis in children: prognostic factors.
AB  - To study the clinical course and the predictors of outcome in children and
      adolescents, 39 patients with nephrotic syndrome and primary focal segmental
      glomerulosclerosis (FSGS) were followed for a mean of 84.6 months. Thirty-six
      patients were treated with prednisone, either alone or in conjunction with
      cyclophosphamide. The clinical course was one of sustained remission in 4
      patients, frequent relapse in 13, persistent nonnephrotic proteinuria in 5, and
      persistent nephrotic syndrome in 17; 2 patients had stable renal failure and 8
      had progressive renal failure, 5 of them evolving to end-stage renal failure
      (ESRF). Resistance to prednisone was recorded in 76.6% of patients. The use of
      cyclophosphamide plus prednisone was of benefit in 42.8% of patients; 22.2% of
      the prednisone-resistant patients achieved remission of the nephrotic syndrome. A
      Kaplan-Meier analysis revealed a survival rate of 92% after 5 years, 86% after 10
      years, and 76% after 15 years. Using both univariate and multivariate analysis,
      persistent nephrotic syndrome was associated with progression to ESRF and the
      remission of proteinuria with maintenance of renal function. As the outcome of
      the nephrotic syndrome in FSGS is significantly improved by remission of
      proteinuria, it is conceivable that immunosuppressive medication may be used in
      conjunction with prednisone in patients with steroid resistance.

PMID- 11519898
TI  - Combined pharmacotherapy for nocturnal enuresis.
AB  - Nocturnal enuresis is a common childhood disorder. Tricyclic antidepressants and
      anticholinergic agents have been the well accepted pharmacological treatment for
      this disorder and are efficacious in 40-70% and 10-50% of cases, respectively.
      The present study was performed to evaluate the effect of a combined treatment of
      tricyclic antidepressant and an anticholinergic agent. Twenty-two children aged 6
      12 years with primary monosymptomatic nocturnal enuresis who did not prefer to
      use a conditioning alarm were given a combined treatment of these drugs. After a
      control period of 1 month, each patient was treated for 6 months and then
      observed for 3 months. A 30-mg dose of amitriptyline or imipramine was given with
      either 2-4 mg oxybutinin or 10-20 mg propiverine. Efficacy was determined
      relative to the number of wet nights per week compared with the control period,
      with more than a 50% decrease in wet nights per week taken to indicate efficacy.
      The mean wet nights per week decreased from 6.1 to 1.7 (P<0.01), and efficacy was
      established in 20 patients (90.9%). Relapses occurred in 60.0% of patients during
      the follow-up period. No significant side effects were observed. The efficacy of
      the combined therapy in monosymptomatic nocturnal enuresis appears to be greater
      than that reported for either drug alone, and therefore can be a choice of
      treatment in order to motivate children with nocturnal enuresis.

PMID- 11519899
TI  - Hypercalciuria in ex-preterm children, aged 7-8 years.
AB  - In a previous study, 8 of 28 ex-preterm infants, aged 4-5 years, had increased
      urinary calcium excretion. The aim of this study was to confirm this finding and
      to determine if raised urinary calcium excretion is associated with reduced bone
      mineralisation. Forty-six ex-preterm children, aged 7-9 years, and 40 age- and
      sex-matched controls were recruited. The calcium excretion measured from 3
      separate 24-h urine collections was recorded and a dietary assessment made from a
      diary record. Data were retrieved from the neonatal case notes and included
      aminoglycoside usage. Dual energy X-ray absorptiometry was used to measure bone
      mineral content and bone mineral density (BMD) in all children. The mean maximum
      24-h urinary calcium was significantly higher in the preterm group than the term
      group (P=0.01). Increased calcium excretion was associated with raised neonatal
      aminoglycoside levels (P=0.0013). Height standard deviation score and hip BMD
      were significantly lower in the 21 preterm children with a 24-h urinary calcium
      above 4 mg/kg per day than term controls (P=0.04 and P=0.004, respectively).
      Urinary calcium excretion had a negative relationship with hip BMD in the preterm
      group (P=0.004). This difference in BMD was not observed in the 25 preterm
      children with normocalciuria. In the 10 preterm girls with hypercalciuria, hip
      BMD was lower than in control females (P=0.01). This difference in hip BMD
      between the 11 preterm boys with hypercalciuria and term boys was not significant
      (P=0.05). In conclusion, preterm children are shorter and have a lower hip BMD
      than those with normocalciuria. Further prospective studies are required to
      assess this risk and its influence on subsequent impaired bone mineralisation.

PMID- 11519900
TI  - Systemic lupus erythematosus and thrombotic thrombocytopenic purpura: a case and
      review.
AB  - Thrombotic thrombocytopenic purpura (TTP) is rare in children with systemic lupus
      erythematosus (SLE). We report a 15-year-old female who simultaneously presented
      with TTP and SLE. Kidney biopsy showed membranous nephropathy. Her condition
      improved with plasmapheresis, intravenous cyclophosphamide, and prednisone pulse
      therapy. We also reviewed the literature for this association in pediatric
      patients comparing presenting sequence and renal pathology with cases documented
      in the adult literature.

PMID- 11519901
TI  - Immunologic tolerance.
AB  - Immunologic tolerance, an active state of antigen specific non-responsiveness, is
      important in understanding autoimmune diseases and the potential for transplant
      acceptance. Recent progress in basic studies and preclinical models involving
      mixed chimerism, costimulatory blockade, immune deviation, and HLA derived
      peptides suggest that clinical applications are now possible. The National
      Institutes of Health and Juvenile Diabetes Research Foundation recently launched
      an Immune Tolerance Network made up of investigators from around the world to
      develop clinical trials in immune tolerance in autoimmune disease,
      transplantation and allergy. This review highlights historical perspectives and
      recent progress in induction and maintenance of immunologic tolerance relevant to
      pediatric nephrology.

PMID- 11519902
TI  - The continued care of children with renal disease into adult life.
AB  - Today in developed countries the majority of paediatric patients in hospital
      units suffer from conditions which will continue into adult life, and paediatric
      nephrology is no exception to this. Despite its obvious importance, the problem
      of the transition of these children with continuing renal diseases from
      paediatric to adult clinics is little discussed and often timed and managed
      badly, with failures on the part of both paediatricians and internists. However,
      a number of simple principles and actions can help to make the transition more
      successful and avoid medical and psychological harm. Nephrology can learn from
      the similar experience in other areas of paediatrics and medicine, such as
      diabetes, congenital heart disease and cystic fibrosis. Access to facilities for
      adolescent medicine remains limited and needs to be expanded. Whilst the
      management of those clearly needing continued care remains paramount, in addition
      guidelines for the follow-up management of apparently well young adults following
      attacks of conditions such as Henoch-Schonlein purpura, the haemolyticuraemic
      syndrome and acute renal failure are needed.

PMID- 11519903
TI  - HUS or not HUS?

PMID- 11519904
TI  - Paucisymptomatic hemolytic-uremic syndrome or shigatoxin-associated
      glomerulonephritic syndrome?

PMID- 11519905
TI  - Follow-up of two children with basement membrane abnormalities.

PMID- 11519906
TI  - Could the effective mechanisms of retinoids on nephrogenesis be also operative on
      the amelioration of injury in acquired renal lesions?

PMID- 11519907
TI  - Detection of carriage of vancomycin-resistant enterococci in an intensive care
      unit in Buenos Aires.

PMID- 11519908
TI  - Nelfinavir in expanded postexposure prophylaxis causing acute hepatitis with
      cholestatic features: two case reports.

PMID- 11519909
TI  - Prevention of postoperative wound infections: to cover up?

PMID- 11519910
TI  - Routes and sources of Staphylococcus aureus transmitted to the surgical wound
      during cardiothoracic surgery: possibility of preventing wound contamination by
      use of special scrub suits.
AB  - OBJECTIVES: To trace the routes of transmission and sources of Staphylococcus
      aureus found in the surgical wound during cardiothoracic surgery and to
      investigate the possibility of reducing wound contamination, with regard to total
      counts of bacteria and S. aureus, by wearing special scrub suits. METHODS: A
      total of 65 elective operations for coronary artery bypass graft with or without
      concomitant valve replacement were investigated. All staff present in the
      operating room wore conventional scrub suits during 33 operations and special
      scrub suits during 32 operations. Bacteriological samples were taken from the
      hands of the scrubbed team after surgical scrub but before putting on sterile
      gowns and gloves and from the patients' skin (incisional area of sternum and vein
      harvesting area of legs) after preoperative skin preparation with chlorhexidine
      gluconate. Air samples were taken during operations. Bacteriological samples also
      were taken from the subcutaneous walls of the surgical wound just before closing
      the wound. Total counts of bacteria on sternal skin and wound walls (colony
      forming units [CFUs]/cm2) were calculated, as well as total counts of bacteria in
      the air (CFUs/m3). Strains of S. aureus recovered from the different sampling
      sites were compared by pulsed-field gel electrophoresis (PFGE). RESULTS: Special
      scrub suits significantly reduced total counts of bacteria in air compared to
      conventional scrub suits (P=.002). The number of air samples in which S. aureus
      was found was significantly reduced by special scrub suits compared with
      conventional scrub suits (P=.016; relative risk, 4.4; 95% confidence interval
      [CI95], 1.3-14.91). By use of PFGE, it was possible to identify two cases of
      possible airborne transmission of S. aureus when wearing conventional scrub
      suits, whereas no case was found when wearing special scrub suits. When exposed
      to airborne S. aureus, the concomitant sternal carriage of S. aureus was a risk
      factor for having S. aureus in the wound. CONCLUSIONS: Use of tightly woven
      special scrub suits reduces the dispersal of total counts of bacteria and of S.
      aureus from staff in the operating room, thus possibly reducing the risk of
      airborne contamination of surgical wounds. The importance of careful preoperative
      disinfection of the patient's skin should be stressed.

PMID- 11519911
TI  - Factors associated with postoperative infection.
AB  - OBJECTIVE: We have developed and analyzed a large surgical prophylaxis database
      and now report the factors significantly associated with early infection,
      readmission due to infection, and death within 28 days of surgery. This study is
      intended to be a stepping-stone for further studies using our clinical database.
      DESIGN AND SETTING: A computerized database of 9,016 surgical patients from a 400
      bed community hospital was examined. Multivariate logistic regression and tree
      based modeling were used to identify factors associated with the outcomes.
      Factors considered included surgical procedure, prophylactic antibiotic, age,
      gender, serum creatinine, and albumin. RESULTS: 12.6% had an early infection,
      2.5% were readmitted due to infection, and 2.5% died within 28 days. Most
      combination prophylactic antibiotics were associated with an increased
      probability of an early infection. Decreased albumin and increased age were
      associated with an increased probability of an early infection. Tracheostomy and
      amputations were associated with an increased probability of an early infection,
      whereas gallbladder and orthopedic procedures involving the arm were associated
      with a decreased probability. Factors associated with readmission due to
      infection included dialysis shunt, vascular repair, and an early infection.
      Factors associated with increased probability of death within 28 days included
      age, albumin, serum creatinine, and an early infection. Gallbladder procedures
      and obstetric-gynecologic procedures were associated with a decreased probability
      of death within 28 days. DISCUSSION: Older patients and those with a decreased
      albumin were most likely to have an early infection. To the extent that an early
      infection was a significant risk factor for readmission due to infection, the
      impact of age and albumin on the probability of readmission due to infection is
      demonstrated by their effects on early infections. Interestingly, albumin and age
      were significantly associated with death within 28 days, in addition to early
      infection, showing the predictive association between these factors and early
      death.

PMID- 11519912
TI  - Anesthesia-associated carbon monoxide exposures among surgical patients.
AB  - OBJECTIVE: To estimate the extent of, and evaluate risk factors for, elevated
      carboxyhemoglobin levels among patients undergoing general anesthesia and to
      identify the source of carbon monoxide. DESIGN: Matched case-control study to
      measure carboxyhemoglobin levels. SETTING: Large academic medical center.
      PARTICIPANTS: 45 surgical patients who underwent general anesthesia RESULTS: Case
      patients were more likely than controls to undergo surgery on Monday or Tuesday
      (10/15 vs 7/30; matched odds ratio [mOR], 7.7; 95% confidence interval [CI95],
      1.8-34; P=.01), in one particular room (7/15 vs 4/30; mOR, 8.5; CI95, 1.5-48;
      P=.03) or in a room that was idle for > or =24 hours (11/15 vs 1/30; mOR, 95.5;
      CI95, 8.0-1,138; P< or =.001). In a multivariate model, only rooms, and hence the
      anesthesia equipment, that were idle for > or =24 hours were independently
      associated with elevated intraoperative carboxyhemoglobin levels (OR, 22.4; CI95,
      1.5-338; P=.025). Moreover, peak carboxyhemoglobin levels were correlated with
      the length of time that the room was idle (r=0.7; CI95, 0.3-0.9). Carbon monoxide
      was detected in the anesthesia machine outflow during one case-procedure. No
      contamination of anesthesia gas supplies or CO2 absorbents was found.
      CONCLUSIONS: Carbon monoxide may accumulate in anesthesia circuits left idle for
      > or =24 hours as a result of a chemical interaction between CO2-absorbent
      granules and anesthetic gases. Patients administered anesthesia through such
      circuits may be at increased risk for elevated carboxyhemoglobin levels during
      surgery or the early postoperative period.

PMID- 11519913
TI  - Microbiology and risk factors for catheter exit-site and -hub colonization in
      neonatal intensive care unit patients.
AB  - OBJECTIVE: To identify risk factors and describe the microbiology of catheter
      exit-site and hub colonization in neonates. DESIGN: During a period of 2 years,
      we prospectively investigated 14 risk factors for catheter exit-site and hub
      colonization in 862 central venous catheters in a cohort of 441 neonates.
      Cultures of the catheter exit-site and hub were obtained using semiquantitative
      techniques at time of catheter removal. SETTING: A neonatal intensive care unit
      at a university hospital. RESULTS: Catheter exit-site colonization was found in
      7.2% and hub colonization in 5.3%. Coagulase-negative staphylococci were
      predominant at both sites. Pathogenic flora were found more frequently at the
      catheter hub (36% vs 14%; P<.05). Through logistic regression, factors associated
      with exit-site colonization were identified as umbilical insertion (odds ratio
      [OR], 8.1; 95% confidence interval [CI95], 2.35-27.6; P<.001), subclavian
      insertion (OR, 54.6; CI95, 12.2-244, P<.001), and colonization of the catheter
      hub (OR, 8.9; CI, 3.5-22.8; P<.001). Catheter-hub colonization was associated
      with total parenteral nutrition ([TPN] OR for each day of TPN, 1.056; CI95, 1.029
      1.083; P<.001) and catheter exit-site colonization (OR, 6.11; CI95, 2.603-14.34;
      P<.001). No association was found between colonization at these sites and
      duration of catheterization and venue of insertion, physician's experience,
      postnatal age and patient's weight, ventilation, steroids or antibiotics, and
      catheter repositioning. CONCLUSION: These data support that colonization of the
      catheter exit-site is associated with the site of insertion and colonization of
      the catheter hub with the use of TPN. There is a very strong association between
      colonization at both catheter sites.

PMID- 11519914
TI  - HACCP and food hygiene in hospitals: knowledge, attitudes, and practices of food
      services staff in Calabria, Italy. Collaborative Group.
AB  - OBJECTIVES: To determine adherence to Hazard Analysis and Critical Control Points
      (HACCP) methods and to evaluate knowledge, attitudes, and practices of food
      services staff with regard to food hygiene in hospitals. DESIGN: A survey.
      PARTICIPANTS: Hospital medical directors and food-services staff of 36 hospitals
      in Calabria, Italy. METHODS: A questionnaire about hospital characteristics, food
      services organization, and measures and procedures for the control and prevention
      of foodborne diseases was sent to medical directors; a questionnaire about
      demographic and practice characteristics, knowledge, attitudes, and behaviors
      about control and prevention of foodborne diseases was sent to food-services
      staff. Multiple logistic regression analysis was performed. RESULTS: Only 54% of
      the 27 responding hospitals were using the HACCP system and, of those using
      HACCP, 79% adopted a food-hygiene-practice manual; more than one half already had
      developed written procedures for food storage, personal hygiene, cleaning and
      disinfection; one half or less performed microbiological assessment of foods and
      surfaces. Of the 290 food-services staff who responded, 78.8% were aware of the
      five leading foodborne pathogens; this knowledge was significantly higher among
      those with a higher educational level and those who worked in hospitals that had
      implemented the HACCP system. Younger staff and those who had attended continuing
      educational courses about food hygiene and hospital foodborne diseases had a
      significantly higher knowledge of safe temperatures for food storage. A positive
      attitude toward foodborne-diseases prevention was reported by the great majority,
      and it was significantly higher in older respondents and in those working in
      hospitals with a lower number of beds. Only 54.9% of those involved in touching
      or serving unwrapped raw or cooked foods routinely used gloves during this
      activity; this practice was significantly greater among younger respondents and
      in those working in hospitals using HACCP. CONCLUSION: Full implementation of the
      HACCP system and infection control policies in hospital food services is needed.

PMID- 11519915
TI  - The epidemiology of invasive pulmonary aspergillosis at a large teaching
      hospital.
AB  - OBJECTIVE: To characterize the epidemiology of invasive pulmonary aspergillosis
      (IPA). DESIGN: A retrospective case series. SETTING: An 850-bed, academic,
      tertiary-care medical center. PARTICIPANTS: Adult inpatients, between January 1,
      1990, and December 31, 1998, with either a histopathology report consistent with
      IPA or a discharge diagnosis of aspergillosis. METHODS: We reviewed medical
      records and categorized case-patients as definitive or probable and acquisition
      of IPA as nosocomial, indeterminate, or community using standard definitions. To
      determine the rate of aspergillus respiratory colonization, we identified all
      inpatients who had a respiratory culture positive for Aspergillus species without
      a histopathology report consistent with IPA or a discharge diagnosis of
      aspergillosis. Three study intervals were defined: interval 1, 1990 to 1992;
      interval 2, 1993 to 1995; and interval 3, 1996 to 1998. Carpeting in rooms for
      patients following heart-lung and liver transplant was removed and ceiling tiles
      were replaced during interval 1; a major earthquake occurred during interval 2.
      RESULTS: 72 case-patients and 433 patients with respiratory colonization were
      identified. Acquisition was nosocomial for 18 (25.0%), indeterminate for 9
      (12.5%), and community-acquired for 45 (62.5%) case-patients. Seventeen (23.6%)
      of the 72 case-patients had prior transplants, including 15 solid organ and 2
      bone marrow. The IPA rate per 100 solid organ transplants (SOTs) decreased from
      2.45 during interval 1 to 0.93 during interval 2 and to 0.52 during interval 3
      (chi-square for trend, 5.44; P<.05). The hospitalwide IPA rate remained stable at
      0.03 per 1,000 patient days. CONCLUSIONS: The SOT IPA rate decreased after
      intervals 1 and 2, although the hospitalwide IPA rate remained stable during the
      study period. Post-earthquake hospital demolition and construction occurring
      after interval 2 was not associated with an increase in the rate of IPA at our
      institution.

PMID- 11519916
TI  - Do new surgeons have higher surgical-site infection rates?
AB  - We compared class I surgical-site infection (SSI) rates for new and experienced
      surgeons. Data showed that new surgeons in two surgical subspecialties associated
      with higher baseline SSI rates had rates higher than their experienced
      colleagues. They took longer in the operating room (OR), but did not operate on
      sicker patients. As the surgeons gained more experience (as measured by
      cumulative cases), their OR times and SSI rates decreased toward their
      colleagues'. New surgeons who perform infection-prone surgery may have higher SSI
      rates than more experienced colleagues until they gain experience. A new
      surgeon's SSI rate could be one factor considered in assessing competence.

PMID- 11519917
TI  - Two-year trends of peripherally inserted central catheter-line complications at a
      tertiary-care hospital: role of nursing expertise.
AB  - We found reductions in peripherally inserted central catheter (PICC) complication
      rates over 2 years of observation (20.4 vs 13.8/1,000 line-days; relative risk,
      0.5-0.9). This difference represents a cost saving due to reduced line
      reinsertions and reduced use of thrombolytic agents. The presence of a dedicated
      PICC insertion nursing team and education of ward nurses in PICC maintenance is a
      plausible explanation for the observed differences.

PMID- 11519918
TI  - Differences in antimicrobial susceptibility among hospitals in an integrated
      health system.
AB  - We evaluated the differences in antimicrobial susceptibility among hospitals in
      three different integrated healthcare systems. Each system provided antibiogram
      susceptibility reports from representative hospitals. Reports were analyzed for
      statistically significant differences between hospitals in a given system for
      nine important organisms. We found numerous significant interhospital differences
      in antimicrobial-susceptibility patterns within health systems. For this reason,
      the practice of combining antibiotic-susceptibility data into a systemwide
      antibiogram should be discouraged.

PMID- 11519919
TI  - Bloodborne pathogen exposures in a developmental center: 1993-2000.
AB  - In a developmental center, 257 potential bloodborne pathogen exposures (119
      bites, 91 scratches, 30 sharps injuries, 17 mucosal breaks) occurred during 8
      years (13,187 employee-years and 6,980 resident-years). Of the residents, 9% were
      hepatitis B virus (HBV) surface antigen carriers. Serological follow-up of
      exposed, susceptible employees and residents identified no transmission of HBV,
      hepatitis C virus (HCV), or human immunodeficiency (HIV) virus. This outcome has
      been due primarily to hepatitis B immunization and low prevalences of HCV or HIV
      infections among the subjects. Proper follow-up of all potential exposures is
      crucial to identify transmission promptly, allay anxiety, and prevent unwarranted
      workmen's compensation claims. Measures are suggested to reduce exposure further.

PMID- 11519920
TI  - Nosocomial infections in a community hospital in Mexico.
AB  - Results from prospective surveillance of nosocomial infections (NIs) in a small
      community hospital were evaluated, and a case-control study was conducted. The
      rate of 1.4 NIs per 100 discharges determined by prospective surveillance was
      found to be underestimated. Prematurity, pediatric service, surgery, length of
      stay, and age were independently associated with NI.

PMID- 11519921
TI  - Infrequent isolation of multiresistant Acinetobacter baumannii from the staff
      tending a colonized patient with severe burns.
AB  - A patient with severe burns who was colonized by multiresistant Acinetobacter
      baumannii was cared for in contact isolation by staff intensively trained on
      hospital hygiene. Of the 1,907 postexposure cultures from the staff and 425
      environmental samples, only 0.7% and 4%, respectively, yielded this
      microorganism. These data show that strict hygienic measures may limit staff
      colonization and contamination of the environment byA baumannii.

PMID- 11519922
TI  - The effects of contamination on biological monitoring.
AB  - We investigated the frequency and patterns of biological-monitoring-test
      contamination and the effect of contamination on the growth of test organisms.
      Overall, the contamination rate was 0.81%, but the rate of contamination varied
      significantly by sterilization method. Contamination did not appear to inhibit
      growth of test organisms.

PMID- 11519924
TI  - FDA: reuse of single-use devices.

PMID- 11519923
TI  - Surveillance of hospital-acquired infection in England, Germany, and The
      Netherlands: will international comparison of rates be possible?
AB  - Three national surveillance systems for nosocomial infection have been developed
      independently and implemented successfully in England, Germany, and The
      Netherlands. All three are based on the American National Nosocomial Infections
      Surveillance System and have adopted a surveillance strategy that is targeted at
      specific infections or groups of patients for limited time periods. Case-finding
      methods, the minimum data set, and analysis of data are similar and could be
      standardized easily. Resolution of the differences in the definitions of
      infection, the study population, and follow-up should make possible the
      international comparison of infection rates. Such comparisons may identify
      differences in healthcare practices between countries and suggest areas for
      improvement.

PMID- 11519925
TI  - Prejudice and perception: the role of automatic and controlled processes in
      misperceiving a weapon.
AB  - Two experiments used a priming paradigm to investigate the influence of racial
      cues on the perceptual identification of weapons. In Experiment 1, participants
      identified guns faster when primed with Black faces compared with White faces. In
      Experiment 2, participants were required to respond quickly, causing the racial
      bias to shift from reaction time to accuracy. Participants misidentified tools as
      guns more often when primed with a Black face than with a White face. L. L.
      Jacoby's (1991) process dissociation procedure was applied to demonstrate that
      racial primes influenced automatic (A) processing, but not controlled (C)
      processing. The response deadline reduced the C estimate but not the A estimate.
      The motivation to control prejudice moderated the relationship between explicit
      prejudice and automatic bias. Implications are discussed on applied and
      theoretical levels.

PMID- 11519926
TI  - Stereotype distinctiveness: how counterstereotypic behavior shapes the self
      concept.
AB  - Three experiments examined the relationship between distinctiveness and self
      schematicity. Experiment 1 revealed that people were more likely to be self
      schematic in domains of strong performance when they felt distinct from family
      and peers in those domains. Experiments 2 and 3 extended this finding into the
      arena of stereotypes by demonstrating that people were more likely to be self
      schematic in domains of strong performance when their performance was
      counterstereotypic rather than stereotypic. In particular, African Americans and
      women were more likely to be schematic for intelligence than Caucasians and men
      if they performed well academically, whereas Caucasians-especially men-were more
      likely than African Americans to be schematic for athletics if they performed
      well athletically. These results suggest that counterstereotypic behavior plays a
      uniquely powerful role in the development of the self-concept.

PMID- 11519927
TI  - Chronic and temporarily activated causal uncertainty beliefs and stereotype
      usage.
AB  - In 3 studies, we examined the hypothesis that the effects of stereotype usage on
      target judgments are moderated by causal uncertainty beliefs and related accuracy
      goal structures. In Study 1, we focused on the role of chronically accessible
      causal uncertainty beliefs as predictors of a target's level of guilt for an
      alleged academic misconduct offense. In Study 2, we examined the role of chronic
      causal uncertainty reduction goals and a manipulated accuracy goal; in Study 3,
      we investigated the role of primed causal uncertainty beliefs on guilt judgments.
      In all 3 studies, we found that activation of causal uncertainty beliefs and
      accuracy concerns was related to a reduced usage of stereotypes. Moreover, this
      reduction was not associated with participants' levels of perceived control,
      depression, state affect, need for cognition, or personal need for structure.
      Results are discussed in terms of their implications for the model of causal
      uncertainty and, more generally, in terms of the motivational processes
      underlying stereotype usage.

PMID- 11519928
TI  - Culture effects on adults' earliest childhood recollection and self-description:
      implications for the relation between memory and the self.
AB  - American and Chinese college students (N = 256) reported their earliest childhood
      memory on a memory questionnaire and provided self-descriptions on a shortened 20
      Statements Test (M. H. Kuhn & T. S. McPartland, 1954). The average age at
      earliest memory of Americans was almost 6 months earlier than that of Chinese.
      Americans reported lengthy, specific, self-focused, and emotionally elaborate
      memories; they also placed emphasis on individual attributes in describing
      themselves. Chinese provided brief accounts of childhood memories centering on
      collective activities, general routines, and emotionally neutral events; they
      also included a great number of social roles in their self-descriptions. Across
      the entire sample, individuals who described themselves in more self-focused and
      positive terms provided more specific and self-focused memories. Findings are
      discussed in light of the interactive relation between autobiographical memory
      and cultural self-construal.

PMID- 11519929
TI  - When do individuals help close others improve? The role of information
      diagnosticity.
AB  - On the basis of the self-evaluation maintenance model (SEM; Tesser, 1988), it was
      hypothesized that individuals give less improving information to relationally
      close (rather than distant) others, out of concern for being outperformed by
      close others in the future. Further, this effect only occurs if diagnostic and
      valid criteria for success are present. Three studies confirmed the hypotheses.
      In Studies 1 and 2, participants gave less improving information to familiar than
      to unfamiliar others in a domain (academics) in which diagnostic assessment
      criteria (grades) were available. This pattern was not found in a domain (social
      life) without diagnostic criteria. These results were replicated in Study 3, in
      which relative performance and diagnosticity of assessment criteria were
      manipulated and amount of improving information given to friends and strangers
      was measured. Diagnosticity of comparison information is an important addition to
      the SEM model.

PMID- 11519930
TI  - Love and the commitment problem in romantic relations and friendship.
AB  - On the basis of the proposition that love promotes commitment, the authors
      predicted that love would motivate approach, have a distinct signal, and
      correlate with commitment-enhancing processes when relationships are threatened.
      The authors studied romantic partners and adolescent opposite-sex friends during
      interactions that elicited love and threatened the bond. As expected, the
      experience of love correlated with approach-related states (desire, sympathy).
      Providing evidence for a nonverbal display of love, four affiliation cues (head
      nods, Duchenne smiles, gesticulation, forward leans) correlated with self-reports
      and partner estimates of love. Finally, the experience and display of love
      correlated with commitment-enhancing processes (e.g., constructive conflict
      resolution, perceived trust) when the relationship was threatened. Discussion
      focused on love, positive emotion, and relationships.

PMID- 11519931
TI  - Self-control and accommodation in close relationships: an interdependence
      analysis.
AB  - Accommodation refers to the willingness, when a partner has engaged in a
      potentially destructive behavior, to (a) inhibit impulses toward destructive
      responding and (b) instead respond constructively. A pilot study and 3 additional
      studies examined the hypothesis that self-control promotes individuals' ability
      to accommodate in response to a romantic partner's potentially destructive
      behavior. Dispositional self-control was positively associated with accommodative
      tendencies in all 4 investigations. In addition, Study 1 (a retrospective study)
      and Study 2 (a laboratory experiment) revealed that "in-the-moment" self
      regulatory strength depletion decreased the likelihood that an individual would
      accommodate. Finally, Study 3 demonstrated that self-control exerted a
      significant effect on accommodation even after the authors included commitment to
      the relationship in the model. Implications for relationship functioning are
      discussed.

PMID- 11519932
TI  - Attention to behavioral events during interaction: two actor-observer gaps and
      three attempts to close them.
AB  - In social interactions, people must pay attention to many behavioral events
      unfolding in themselves and the other person-events that can be observable or
      unobservable, intentional or unintentional. Three studies explored how people
      distribute their attention to these different event types and, as a result, build
      up representations of self and partner during the interaction. Relying on basic
      principles of attention, the authors predicted 2 actor-observer gaps: Actors pay
      more attention to unobservable events and less to observable events than do
      observers, and actors pay more attention to unintentional events and less to
      intentional events than do observers. Study 1 documents both gaps. Studies 2 and
      3 explore factors that might close the gaps, such as relational intimacy and
      empathy. Implications of these results for the role of attention in attribution
      and interpersonal behavior are discussed.

PMID- 11519933
TI  - Covariance structure of neuroticism and agreeableness: a twin and molecular
      genetic analysis of the role of the serotonin transporter gene.
AB  - The Revised NEO Personality Inventory domains of Neuroticism and Agreeableness
      are considered factorially distinct despite several intercorrelations between
      these domains. The genetic correlation, an index of the degree to which these
      intercorrelations are caused by genetic influences, was estimated using data from
      913 monozygotic and 562 dizygotic volunteer twin pairs from Canada, Germany, and
      Japan. The serotonin transporter gene, 5-HTTLPR, was assayed in a sample of 388
      nontwin sibling pairs from the United States to determine the contribution of the
      serotonin transporter locus to the covariation between the Neuroticism and
      Agreeableness scales. In all four samples, genetic influences contributed to the
      covariance of Neuroticism and Agreeableness, with the serotonin transporter gene
      accounting for 10% of the relationship between these domains.

PMID- 11519934
TI  - The affective component of the secure base schema: affective priming with
      representations of attachment security.
AB  - Using an affective priming procedure (S. T. Murphy & R. B. Zajonc, 1993), 7
      studies examined the effects of the contextual activation of representations of
      attachment security (secure base schema) on the evaluation of neutral stimuli
      under either neutral or stressful contexts. In all the studies, participants also
      reported on their attachment style. Results indicated that the subliminal priming
      of secure base representations led to more positive affective reactions to
      neutral stimuli than did the subliminal priming of neutral or no pictures under
      both neutral and stressful contexts. Although the subliminal priming of
      positively valued, attachment-unrelated representations heightened positive
      evaluations under neutral contexts, it failed to elicit positive affect under
      stressful contexts. The results also revealed interesting effects of attachment
      style. The discussion focuses on the affective component of the secure base
      schema.

PMID- 11519935
TI  - Gender differences in personality traits across cultures: robust and surprising
      findings.
AB  - Secondary analyses of Revised NEO Personality Inventory data from 26 cultures (N
      = 23,031) suggest that gender differences are small relative to individual
      variation within genders; differences are replicated across cultures for both
      college-age and adult samples, and differences are broadly consistent with gender
      stereotypes: Women reported themselves to be higher in Neuroticism,
      Agreeableness, Warmth, and Openness to Feelings, whereas men were higher in
      Assertiveness and Openness to Ideas. Contrary to predictions from evolutionary
      theory, the magnitude of gender differences varied across cultures. Contrary to
      predictions from the social role model, gender differences were most pronounced
      in European and American cultures in which traditional sex roles are minimized.
      Possible explanations for this surprising finding are discussed, including the
      attribution of masculine and feminine behaviors to roles rather than traits in
      traditional cultures.

PMID- 11519936
TI  - The consequences of pairing questions: context effects in personality
      measurement.
AB  - The effect of context on responses to questions has been a prominent focus in
      social and political survey research. However, little investigation of context
      effects has been done for the measurement of psychological constructs. A measure
      of anger experience and expression in development uses vignettes describing
      interpersonal situations that provoke varying degrees of anger and require
      respondents to indicate their affective and/or expressive response to the
      situation. In this study, the consequences of pairing the two questions for each
      vignette are investigated. Pairing the anger-experience and likelihood-of
      expression questions changes the item's context. Item response theory analysis
      similar to that used to detect differential item functioning was performed. For
      some of the items, responding to a single or paired question affected the
      extremity of responses. The findings are discussed in terms of their implications
      for personality measurement.

PMID- 11519937
TI  - Understanding extraverts' enjoyment of social situations: the importance of
      pleasantness.
AB  - Extraversion is a broad, multifaceted trait, yet researchers are still unsure of
      its defining characteristics. One possibility is that the essential feature of
      extraversion is the tendency to enjoy social situations. An alternative
      possibility is that extraversion represents sensitivity to rewards and the
      tendency to experience pleasant affect. In three studies, participants rated
      situations that varied on two dimensions: (a) whether they were social or
      nonsocial and (b) whether they were very pleasant, moderately pleasant,
      moderately unpleasant, or very unpleasant. Extraverts only rated social
      situations more positively than introverts did when the situations were pleasant,
      and extraverts also rated nonsocial situations more positively than introverts
      did if the situations were pleasant. Thus, the pleasantness of situations was
      more important than whether they were social or nonsocial in determining
      extraverts' and introverts' enjoyment.

PMID- 11519938
TI  - Folding/unfolding/refolding of proteins: present methodologies in comparison with
      capillary zone electrophoresis.
AB  - A series of techniques for monitoring protein folding/unfolding/misfolding
      equilibria are here assessed and compared with capillary zone electrophoresis
      (CZE). They include spectroscopic techniques, such as circular dichroism,
      intrinsic fluorescence, nuclear magnetic resonance, Fourier transform infrared
      and Raman spectroscopy, small-angle X-ray scattering, as well as techniques based
      on biological assays, such as limited proteolysis and immunochemical analysis of
      different conformational states. Some unusual probes, such as mass spectrometry
      for probing unfolding transitions, are also discussed. Size-exclusion
      chromatography is also evaluated in view of the fact that this technique, like
      all electrophoretic techniques, and unlike spectroscopic probes, which can only
      see an average signal in mixed populations, can indeed physically separate folded
      vs. unfolded macromolecules, especially in the case of slow equilibria.
      Particular emphasis is devoted to electrophoretic techniques, such as gel-slab
      electrophoresis in transverse urea or thermal gradients, and CZE. In the latter
      case, a number of applications are shown, demonstrating the excellent correlation
      of CZE with more traditional probes, such as intrinsic fluorescence monitoring.
      It is additionally shown that CZE can be used for measuring the deltaG degrees of
      unfolding over the pH scale, in good agreement with theoretical calculations on
      the electrostatic free energy of folding vs. pH, as calculated with a linearized
      Poisson-Boltzmann equation. Finally, it is demonstrated that CZE can probe also
      aggregate formation in the presence of helix-inducing agents, such as
      trifluorethanol.

PMID- 11519939
TI  - On-line sample preconcentration in capillary electrophoresis, focused on the
      determination of proteins and peptides.
AB  - This overview highlights the possibilities of on- or in-line preconcentration
      procedures in combination with a CZE separation, focused on the determination of
      peptides and proteins. The discussed methods, including sample stacking, field
      amplified injection, isotachophoresis, solid phase extraction, membrane
      preconcentration, electroextraction, supported liquid membranes, hollow fibers,
      immunoaffinity, and molecularly imprinted polymers technology preconcentration
      are categorized in electrophoresis-based and chromatography-based
      preconcentration. The chromatography-based preconcentration is subdivided in low
      specificity and high-specificity methods. A number of preconcentration methods
      are available, however, this paper demonstrates that various compounds in
      different media (aqueous solutions, urine, and plasma) require different
      preconcentration systems. The preconcentration techniques of first choice in
      general seem to be solid-phase extraction and membrane preconcentration, because
      of their high concentration ability, multiapplicability, relative simplicity and
      clean-up capability. For the future, hollow fibers seem to hold a great potential
      as preconcentration technique, yielding high concentration factors, using simple
      designs. New techniques, such as hollow fibers, molecularly imprinted polymers
      technology and supported liquid membranes may have the potential to supersede the
      conventional preconcentration techniques in some cases. The larger the arsenal of
      preconcentration techniques becomes, the more efficiently peptides and proteins
      may be analyzed in the future. These techniques, in some cases, require pre
      cleanup procedures, to ensure the purity of the samples to concentrate.

PMID- 11519940
TI  - Microparticles for selective protein determination in capillary electrophoresis.
AB  - A system for detection of trace amounts of protein was developed. Two different
      monoclonal antibodies against human chorionic gonadotropin (hCG) were covalently
      bound to latex particles. When the latex particles were mixed with a sample
      containing hCG, a latex-protein-latex complex (immunocomplex) was formed. The
      complex was separated from the single latex particles using capillary
      electrophoresis and detected using UV-Vis detection. Limit of detection was 8
      amol hCG. The separation was also monitored in real time using laser induced
      fluorescence - charge coupled device (LIF-CCD) imaging detection. However, a
      limitation of the method is the restriction to detection of proteins for which
      monoclonal antibodies are available.

PMID- 11519941
TI  - Detection of specific antibodies using immunosubtraction and capillary
      electrophoresis instrumentation.
AB  - Solution-phase immunoassays based on capillary electrophoresis (CE) separations
      have been shown to be rapid and simple to perform. The potential for sample
      matrix interference and incompatibility with multiplexing conditions for antibody
      detection when dealing with real samples, however, has prompted the development
      of an assay that utilizes an immunosubtraction methodology. A model assay for the
      detection of specific antibodies that relies on solid-phase extraction, CE and
      laser-induced fluorescence (LIF) detection is described. The method, called
      immunocapture-immunosubtraction (ICIS), incorporates an antibody
      capture/purification protocol using magnetic particles. The detection of specific
      antibodies is achieved by CE-LIF analysis of a probe solution following
      incubation with the captured antibodies. As an example of the ICIS assay's
      capabilities, the relative quantification of anti-fluorescein in serum is
      presented.

PMID- 11519942
TI  - Separation of peptides utilizing ultrahigh-temperature micellar electrokinetic
      chromatography.
AB  - The use of ultrahigh column temperatures, up to 110 degrees C, in micellar
      electrokinetic capillary chromatography was investigated. The number of plates
      generated per unit time increased from 0.22 to 12.8 plates/s for separations at
      15 degrees C and 110 degrees C, respectively. Ultrahigh-temperature micellar
      electrokinetic capillary chromatography was used for the separation of cyclic
      undecapeptides (cyclosporins). A minimum resolution of 1.39 was calculated for a
      critical peak pair at 110 degrees C, which is more than a 50% increase over
      resolution generated at 40 degrees C. During a run time of more than 90 min at
      110 degrees C and at pH 9.3, no sample degradation or solvent boiling was
      observed.

PMID- 11519943
TI  - Indocyanine green as a noncovalent, pseudofluorogenic label for protein
      determination by capillary electrophoresis.
AB  - Indocyanine green (ICG)--a negatively charged, polymethine dye--can interact
      noncovalently with proteins to form fluorescent complexes, with excitation and
      emission maxima near 780 and 820 nm, respectively. This behavior was realized
      utilizing either a 100 mM phosphate buffer or a 25 mM citric acid buffer, both at
      pH 3.1. The behavior of ICG under these conditions, termed pseudofluorogenic,
      rendered the dye suitable for use as a label for protein determination in
      capillary electrophoresis with diode laser-induced fluorescence detection (CE
      LIF). To this end, pseudofluorogenic ICG was used both as an on-column label for
      human serum albumin (HSA) and as a precolumn label for a model mixture of
      proteins, including ribonuclease A, transferrin, and cytochrome c. These ICG
      labeled proteins were successfully resolved in less than 11 min, with no
      interference from excess, unbound dye.

PMID- 11519944
TI  - Determination of the cis-trans isomerization barrier of several L-peptidyl-L
      proline dipeptides by dynamic capillary electrophoresis and computer simulation.
AB  - Dynamic capillary electrophoresis (DCE) and computer simulation of the elution
      profiles with the theoretical plate and the stochastic model has been applied to
      determine the isomerization barriers of the three dipeptides L-alanyl-L-proline,
      L-leucyl-L-proline, and L-phenylalanyl-L-proline. The separation of the
      rotational cis-trans isomers has been performed in an aqueous 70 mM borate buffer
      at pH 9.5. Interconversion profiles featuring plateau formation and peak
      broadening were observed. To determine the rate constants k1 and k(-1) of the cis
      trans isomerization in dynamic capillary electrophoresis, equations have been
      derived for the theoretical plate model and stochastic model. The
      electropherograms were simulated with the ChromWin software which uses the
      experimental data plateau height h(plateau), peak width at half height Wh, the
      total migration times of the cis-trans isomers tR and the electroosmotic break
      through time t0 as well as the peak ratio [cis]/[trans]. From temperature
      dependent measurements, the rate constants k1 and k(-1) and the kinetic
      activation parameters deltaG#, deltaH# and deltaS# of the cis-trans isomerization
      of the three dipeptides were obtained.

PMID- 11519945
TI  - Influence of the amino acid sequence and nature of the cyclodextrin on the
      separation of small peptide enantiomers by capillary electrophoresis using
      randomly substituted and single isomer sulfated and sulfonated cyclodextrins.
AB  - The separation of dipeptide and tripeptide enantiomers using negatively charged
      single isomers as well as randomly sulfated and sulfonated cyclodextrins (CDs)
      was investigated with respect to the amino acid sequence of the peptides and the
      nature of the CDs. Standardized conditions concerning buffer pH and molarity, CD
      concentration, and separation voltage were applied. Compared to suffobutylether
      beta-CD and heptakis-(2,3-dimethyl-6-sulfato)-beta-CD, randomly sulfated beta-CD
      as well as the single isomer derivatives heptakis-6-sulfato-beta-CD and heptakis
      (2,3-diacetyl-6-sulfato)-beta-CD were the more universal CDs for
      enantioseparations. The enantiomer migration order depended to a greater extent
      on the CD than on the amino acid sequence of the peptide although small
      structural differences such as formation of a peptide amide or ester affected the
      chiral recognition by the randomly substituted CD derivatives. Using
      sulfobutylether-beta-CD or heptakis-(2,3-diacetyl-6-sulfato)-beta-CD the DD
      enantiomers migrated before the LL enantiomers for most peptides while the
      opposite migration order, i.e. LL before DD, was observed when heptakis-6-sulfato
      beta-CD was applied as chiral selector.

PMID- 11519946
TI  - Diffusion coefficient of DNA molecules during free solution electrophoresis.
AB  - The free-draining properties of DNA normally make it impossible to separate
      nucleic acids by free-flow electrophoresis. However, little is known, either
      theoretically or experimentally, about the diffusion coefficient of DNA molecules
      during free-flow electrophoresis. In fact, many authors simply assume that the
      Nernst-Einstein relation between the mobility and the diffusion coefficient still
      holds under such conditions. In this paper, we present an experimental study of
      the diffusion coefficient of both ssDNA and dsDNA molecules during free-flow
      electrophoresis. Our results unequivocally show that a simplistic use of Nernst
      Einstein's relation fails, and that the electric field actually has no effect on
      the thermal diffusion process. Finally, we compare the dependence of the
      diffusion coefficient upon DNA molecular size to results obtained previously by
      other groups and to Zimm's theory.

PMID- 11519947
TI  - Three-dimensional observation of electrophoretic migration of dsDNA in semidilute
      hydroxyethylcellulose solution.
AB  - Three-dimensional (3-D) video fluorescence microscopy is demonstrated for the
      investigation of biopolymer electrophoretic migration using double-stranded
      (ds)DNA in semidilute hydroxyethylcellulose (HEC) as a test system. It is shown
      that 3-D imaging enables visualization of segmental motion with greater detail
      than is available in conventional video microscopy. A high frame rate (50-110
      frames per second (fps)) intensified progressive scan camera is used to acquire
      fifteen axial sections focused at different depths through the DNA molecule. A 3
      D DNA image is generated from these sections using blind deconvolution image
      reconstruction and motion is represented as a succession of volume images. A 3-D
      extension of the Doi/Oana ellipsoidal model is used to fit the DNA envelope,
      allowing simple quantitative descriptions of the changing shape of the DNA as it
      interacts with the sieving polymer solution. With 3-D views of migrating DNA
      molecules we observe U-shaped conformations oriented at an angle to the
      microscope plane. We are also able to resolve ambiguities and artifacts resulting
      from loss of information from DNA segments that are not in focus.

PMID- 11519948
TI  - Capillary electrophoresis of RNA in dilute and semidilute polymer solutions.
AB  - We report separations of RNA molecules (281-6583 nucleotides) by capillary
      electrophoresis in dilute and semidilute solutions of aqueous
      hydroxyethylcellulose (HEC) ether in varying buffers. RNA mobility and peak band
      widths are examined under both nondenaturing and also denaturing conditions. From
      studies of sieving polymer concentration and chain length, it is found that good
      separations can be obtained in semidilute solutions as well as in dilute
      solutions. The dependence of RNA mobility on its chain length is consistent with
      separation by a similar to transient entanglement mechanism in dilute solutions.
      In semidilute entangled solutions the separation proceeds by segmental motion.

PMID- 11519949
TI  - Glycoscreening by on-line sheathless capillary electrophoresis/electrospray
      ionization-quadrupole time of flight-tandem mass spectrometry.
AB  - An analytical approach based on sheathless on-line coupling of capillary
      electrophoresis (CE) and electrospray ionization (ESI) quadrupole time-of-flight
      (QTOF) mass spectrometry (MS) has been developed for providing new insight into
      the characterization of carbohydrate mixtures. The home-built sheathless CE/

PMID- 11519950
TI  - Identification of oligomeric domains within dermatan sulfate chains using
      differential enzymic treatments, derivatization with 2-aminoacridone and
      capillary electrophoresis.
AB  - Galactosaminoglycans, i.e. dermatan sulfate (DS) and chondroitin sulfate, are
      linear heteropolysaccharides consisting of repeating disaccharide units of L
      iduronic acid (L-IdoA) or D-glucuronic acid (D-GlcA) residues linked to N-acetyl
      galactosamine. High-performance capillary electrophoresis (HPCE or CE) has been
      successfully used for determining the disaccharide composition of
      glycosaminoglycans. However, only limited information is available on how to
      identify oligomeric domains rich in D-GlcA or L-IdoA. The aim of this study was
      therefore to develop a rapid and accurate CE procedure by which such
      oligosaccharides can be determined together with the variously sulfated
      disaccharides. Isolated dermatan sulfates of human origin were separately
      digested with chondroitinases ABC, AC and B and the enzymic products were
      derivatized with 2-aminoacridone. CE analysis of these products was performed
      using a phosphate buffer, pH 3.0, and reversed polarity at 30 kV. The
      derivatization enabled their detection with laser-induced fluorescence (LIF) and
      UV at 260 nm at much higher sensitivity than the detection of nonderivatized
      delta-saccharides at 232 nm and therefore components undetectable at 232 nm were
      nicely detected after derivatization. Except for delta-disaccharides, altogether
      five distinct oligosaccharides with differences in charge density were
      identified. Depending on the lyase that produced these oligomers, information on
      the presence of L-IdoA- or D-GlcA-containing domains within the DS chain and the
      sulfation pattern of these oligomeric domains was obtained. This CE method could
      also be useful in studying the functional oligomeric domains in
      galactosaminoglycan chains.

PMID- 11519951
TI  - Approaches to enhancing the sensitivity of capillary electrophoresis methods for
      the determination of inorganic and small organic anions.
AB  - One of the major problems facing the development of capillary electrophoresis
      (CE) is the relatively high limits of detection when compared to traditional high
      performance liquid chromatographic (HPLC) methods. While the use of an
      alternative detector can offer better sensitivity, a more universal approach is
      sample preconcentration. Numerous on-line methods have been developed to improve
      the sensitivity of CE, and are based on electrophoretic principles,
      chromatographic principles, or a combination of both. This review will discuss
      all forms of on-line preconcentration methods for CE, with emphasis given to
      those that have shown particular merit when applied to inorganic and small
      organic anions.

PMID- 11519952
TI  - Capillary zone electrophoresis for the characterization of latex particles.
AB  - Capillary zone electrophoresis (CZE) was applied to the separation of acrylic
      styrene copolymer emulsion particles. Fast separations could be performed on
      samples containing chemically identical latex particles of different size, as
      well as on samples with particles of the same size but differing in chemical
      composition. The developed method was also used for the analysis of water soluble
      fractions of urethane dispersions. Additionally, the physical interaction between
      different particles (e.g., acrylic and urethane particles) could be studied using
      this method. The separation mechanism is based on the zeta potential of the
      particles and the relaxation effect under the applied analytical conditions.

PMID- 11519953
TI  - Separation of lidocaine and its metabolites by capillary electrophoresis using
      volatile aqueous and nonaqueous electrolyte systems.
AB  - The separation of the basic drug lidocaine and six of its metabolites has been
      investigated both by using volatile aqueous electrolyte system, at low pH and by
      employing non-aqueous electrolyte systems. In aqueous systems, the best
      separation of the compounds under the investigated conditions was achieved by
      using the electrolyte 60 mM trifluoroacetic acid (TFA)/triethylamine (TEA) at pH
      2.5 containing 15% methanol. With this electrolyte, all seven compounds were well
      separated with high efficiency and migration time repeatability. The separations
      with bare fused-silica capillaries and polyacrylamide-coated capillaries were
      compared with higher separation efficiency with the latter. On the other hand,
      near baseline separation of all the seven compounds was also obtained by
      employing the non-aqueous electrolyte, 40 mM ammonium acetate in methanol and TFA
      (99:1, v/v), with comparable migration time repeatability but lower separation
      efficiency relative to the aqueous system.

PMID- 11519955
TI  - Binding constant determination of drugs toward subdomain IIIA of human serum
      albumin by near-infrared dye-displacement capillary electrophoresis.
AB  - Drug binding to serum albumin influences several important pharmacological
      properties such as toxicity, solubility, activity, distribution, and excretion.
      It is therefore of interest to have methodologies that allow for the
      determination of drug-albumin affinity constants while simultaneously providing
      information on the location of the drug binding site. In the present work we
      describe a method for the determination of binding constants of drugs known to
      bind to subdomain IIIA of serum albumin. Drugs used in the study were ketoprofen,
      ibuprofen, quinidine, naproxen, imipramine, and clofibrate. Binding constants of
      the drugs were determined by near-infrared dye-displacement capillary
      electrophoresis. The dye-displacement technique uses a competitive-type
      interaction between the drug of interest and a dye probe to arrive at a binding
      constant. A heptamethine cyanine dye was used as a probe for drug binding at
      subdomain IIIA of serum albumin. The utility of the dye as a noncovalent label
      for serum albumin was investigated. Additionally, the ability of the method to
      illustrate enantioselective binding is shown. The dye displacement technique has
      advantages over current electrophoresis-based techniques in that it is faster and
      uses less reagent.

PMID- 11519954
TI  - Application of capillary zone electrophoresis with off-line solid-phase
      extraction to in vitro metabolism studies of antifungals.
AB  - A simple and robust solid-phase extraction (SPE) procedure for the cleanup and
      sample preconcentration of antifungals (ketoconazole, clotrimazole, itraconazole,
      fluconazole, and voriconazole) and their metabolites after incubation with human
      liver microsomes, as well as a simplified capillary zone electrophoresis (CZE)
      method for their rapid analysis, have been developed to determine the stability
      of these compounds in in vitro samples. Three different sample pretreatment
      procedures using SPE with reversed-phase sorbents (100 mg C8, 100 mg C18, and 30
      mg Oasis-HLB) were studied. The highest and most reproducible recoveries were
      obtained using a 30 mg Oasis-HLB sorbent and methanol containing 2% acetic acid
      as eluent. Enrichment by a factor of about four times was achieved by
      reconstituting the final SPE eluates to a small volume. For the CZE separation,
      good separations without interfering peaks due to the in vitro matrix were
      obtained with a simple running electrolyte using a fused-silica capillary. The
      best separation for all components originated by each tested drug after
      incubation with human liver microsomes (unmetabolized parent drug and its
      metabolites) was obtained using a 0.05 M phosphate running buffer (pH 2.2)
      without additives. The effect of the injection volume was also investigated in
      order to obtain the best sensitivity. Performance levels in terms of precision,
      linearity, limits of detection, and robustness were determined.

PMID- 11519956
TI  - Electrophoretically mediated microanalysis with small molecules: the Jaffe method
      for creatinine carried out in a capillary tube.
AB  - An eletrophoretically mediated microanalysis (EMMA) approach, used to perform
      online chemistry between two small molecules, has been characterized and
      optimized. The "plug-plug" type EMMA method involved electrophoretic mixing and
      subsequent reaction of nanoliter plugs of creatinine-containing samples and
      alkaline picrate (Jaffe reaction) within the confines of the capillary column,
      which acts as a microreactor. Analyses were performed by pressure injecting a
      plug of picrate followed by a plug of the creatinine-containing sample. A
      potential was then applied to electrophoretically mix the two reactants, and an
      incubation time of up to 6 min allowed the reaction to proceed prior to the
      application of a 27 kV separation potential with absorbance detection at 485 nm.
      The use of a 50 microm inner diameter(ID) extended light path capillary (150
      microm pathlength) was found to be adequate for determining elevated levels of
      creatinine in human blood sera, but could not be used to quantify normal levels.
      Quantification of both normal and elevated levels of creatinine in sera was
      possible with a 75 microm ID high-sensitivity cell (1200 microm pathlength).
      Calibration plots using the latter for creatinine in human blood sera spanned the
      expected clinical range and were linear between 40 microM and 1.2 mM (r2 = 0.996)
      with an estimated limit of detection of 17 microM (signal-to-noise ratio S/N =
      3). A quantitative comparison of results obtained with the reported EMMA method
      and accepted clinical methodology correlated very well (slope = 1.001).

PMID- 11519957
TI  - Microchip capillary electrophoresis/electrochemistry.
AB  - Microfabricated fluidic devices have generated considerable interest over the
      past ten years due to the fact that sample preparation, injection, separation,
      derivatization, and detection can be integrated into one miniaturized device.
      This review reports progress in the development of microfabricated analytical
      systems based on microchip capillary electrophoresis (CE) with electrochemical
      (EC) detection. Electrochemical detection has several advantages for use with
      microchip electrophoresis systems, for example, ease of miniaturization,
      sensitivity, and selectivity. In this review, the basic components necessary for
      microchip CEEC are described, including several examples of different detector
      configurations. Lastly, details of the application of this technique to the
      determination of catechols and phenols, amino acids, peptides, carbohydrates,
      nitroaromatics, polymerase chain reaction (PCR) products, organophosphates, and
      hydrazines are described.

PMID- 11519958
TI  - Capillary electrophoresis with on-chip four-electrode capacitively coupled
      conductivity detection for application in bioanalysis.
AB  - Microchip capillary electrophoresis (CE) with integrated four-electrode
      capacitively coupled conductivity detection is presented. Conductivity detection
      is a universal detection technique that is relatively independent on the
      detection pathlength and, especially important for chip-based analysis, is
      compatible with miniaturization and on-chip integration. The glass microchip
      structure consists of a 6 cm etched channel (20 microm x 70 microm cross section)
      with silicon nitride covered walls. In the channel, a 30 nm thick silicon carbide
      layer covers the electrodes to enable capacitive coupling with the liquid inside
      the channel as well as to prevent interference of the applied separation field.
      The detector response was found to be linear over the concentration range from 20
      microM up to 2 mM. Detection limits were at the low microM level. Separation of
      two short peptides with a pI of respectively 5.38 and 4.87 at the 1 mM level
      demonstrates the applicability for biochemical analysis. At a relatively low
      separation field strength (50 V/cm) plate numbers in the order of 3500 were
      achieved. Results obtained with the microdevice compared well with those obtained
      in a bench scale CE instrument using UV detection under similar conditions.

PMID- 11519959
TI  - Capillary electrokinetic separation techniques for profiling of drugs and related
      products.
AB  - Capillary electrokinetic separation techniques offer high efficiency and peak
      capacity, and can be very useful for the analysis of samples containing a large
      variety of (unknown) compounds. Such samples are frequently met in impurity
      profiling of drugs (detection of potential impurities in a pharmaceutical
      substance or product) and in general sample profiling (determination of
      differences or similarities between samples). In this paper, the potential,
      merits, and limitations of electrokinetic separation techniques for profiling
      purposes are evaluated using examples from literature. A distinction is made
      between impurity profiling, forensic profiling and profiling of natural products,
      and the application of capillary zone electrophoresis, micellar electrokinetic
      chromatography, and capillary electrochromatography in these fields is discussed.
      Attention is devoted to important aspects such as selectivity, resolution
      enhancement, applicability, detection, and compound confirmation and
      quantification. The specific properties of the various electrokinetic techniques
      are discussed and compared with more conventional techniques as liquid
      chromatography.

PMID- 11519960
TI  - Capillaries modified by noncovalent anionic polymer adsorption for capillary zone
      electrophoresis, micellar electrokinetic capillary chromatography and capillary
      electrophoresis mass spectrometry.
AB  - A simple coating procedure for generation of a high and pH-independent
      electroosmotic flow in capillary zone electrophoresis (CZE) and micellar
      electrokinetic capillary chromatography (MEKC) is described. The bilayer coating
      was formed by noncovalent adsorption of the ionic polymers Polybrene and
      poly(vinylsulfonate) (PVS). A stable dynamic coating was formed when PVS was
      added to the background electrolyte. Thus, when the PVS concentration in the
      background electrolyte was optimized for CZE (0.01%), the EOF differed less than
      0.3% after 54 runs. The electroosmotic mobility in the coated capillaries was
      (4.9+/-0.1) x 10(-4) cm2V(-1)s(-1) in a pH-range of 2-10 (ionic strength = 30
      mM). When alkaline compounds were used as test substances intracapillary and
      intercapillary migration time variations (n = 6) were less than 1% relative
      standard deviation (RSD) and 2% RSD, respectively in the entire pH range. The
      coating was fairly stable in the presence of sodium dodecyl sulfate, and this
      made it possible to perform fast MEKC separations at low pH. When neutral
      compounds were used as test substances, the intracapillary migration time
      variations (n = 6) were less than 2% RSD in a pH range of 2-9. In addition to
      fast CZE and MEKC separations at low pH, analysis of the alkaline compounds by CE
      MS was also possible.

PMID- 11519961
TI  - On-line identification of trans- and cis-resveratrol by nonaqueous capillary
      electrophoresis/fluorescence spectroscopy at 77 K.
AB  - This work presents a novel method for the accurate determining trans- and cis
      resveratrol (3,5,4'-trihydroxystilbene) by nonaqueous capillary
      electrophoresis/fluorescence spectroscopy at 77 K. The proposed method permits
      not only the separation of resveratrol isomers, but also ensures that on-line
      spectra are readily distinguishable and unambiguously assigned. The experimental
      results also indicate that the effect of nonaqueous capillary electrophoresis
      buffer and low-temperature technique increase the detection limit by more than
      150-fold.

PMID- 11519963
TI  - Analysis of vancomycin and related impurities by micellar electrokinetic
      capillary chromatography. Method development and validation.
AB  - A fast and highly selective micellar electrokinetic capillary chromatography
      (MEKC) method for quantitative analysis of vancomycin and related impurities is
      described. Among the tested surfactants, cetyltrimethylammonium chloride (CTAC)
      offered the best selectivity. Another important parameter, which strongly
      influenced the selectivity, was buffer pH. It was found that the selectivity
      increased with buffer pH decreasing from 9 to 5. Using Tris-phosphate buffer
      containing CTAC, satisfactory separation could be obtained in the pH range from
      5.0 to 5.5. Excellent repeatability in terms of migration time and peak area
      could be obtained when the capillary was carefully washed between two runs. In
      order to obtain optimal conditions and to evaluate the method robustness, a
      central composite experimental design was carried out. The optimal conditions
      were: 44 cm length of fused-silica capillary with 50 microm ID, 120 mM Tris
      phosphate buffer (pH 5.2) containing 50 mM CTAC, -15 kV applied voltage, UV
      detection at 210 nm, and a column temperature of 25 degrees C. Under the optimal
      conditions, more than 20 peaks could be separated within 8 min. The method has a
      linearity range from 0.004 to 1.2 mg/ml (concentration of vancomycin B, active
      component). The limit of detection (LOD) and limit of quantitation (LOQ) were 0.4
      microg/mL vancomycin, equivalent to 0.3 microg/mL vancomycin B (0.04%) and 1.1
      microg/mL vancomycin, equivalent to 0.9 microg/mL vancomycin B (0.1%),
      respectively.

PMID- 11519962
TI  - Determination of iridoid glycosides by micellar electrokinetic capillary
      chromatography-mass spectrometry with use of the partial filling technique.
AB  - A fast and easy method was sought for determination of the iridoid glycosides
      catalpol, ketologanin, verbenalin, loganin, 8-epi-loganic acid, geniposidic acid
      and 10-cinnamoyl catalpol in plant samples. The method involved micellar
      electrokinetic capillary chromatography (MEKC) coupled on-line to mass
      spectrometry. The partial filling technique and electrospray ionization were
      used. Seven iridoid glycosides could be separated with use of MEKC under basic
      conditions. However, 8-epi-loganic acid and geniposidic acid could not be
      detected simultaneously with the five neutral iridoid glycosides by mass
      spectrometry. Therefore, only the neutral iridoid glycosides were screened from
      plant samples. Catalpol, verbenalin, loganin and possibly 10-cinnamoyl catalpol
      were found in an examination of seven plant species in the genera Plantago,
      Veronica, Melampyrum, Succisa, and Valeriana. Aucubin, which was not included in
      the sample mixture used in method development because of overlapping with
      catalpol in MEKC, was also detected. The limits of detection for the iridoid
      glycosides, both at the UV and at the mass spectrometer, are given.

PMID- 11519965
TI  - Enantiomer separation by nonaqueous and aqueous capillary electrochromatography
      on cyclodextrin stationary phases.
AB  - Native beta- and gamma-cyclodextrin bound to silica (ChiraDex-beta and ChiraDex
      gamma) were packed into capillaries and used for enantiomer separation by
      capillary electrochromatography (CEC) under aqueous and nonaqueous conditions.
      Negatively charged analytes (dansyl-amino acids) were resolved into their
      enantiomers by nonaqueous CEC (NA-CEC). The addition of a small amount of water
      to the nonaqueous mobile phase enhanced the enantioselectivity but increased the
      elution time. The choice of the background electrolyte (BGE) determined the
      direction of the electroosmotic flow (EOF). With 2-(N-morpholino) ethanesulfonic
      acid (MES) or triethylammonium acetate (TEAA) as BGE an inverse EOF (anodic EOF)
      was observed while with phosphate a cathodic EOF was found. The apparent pH
      (pH*), the concentration of the BGE, and the nature of the mobile phase strongly
      influenced the elution time, the theoretical plate number and the chiral
      separation factor of racemic analytes.

PMID- 11519964
TI  - Capillary electrochromatography with polyacrylamide monolithic stationary phases
      having bonded dodecyl ligands and sulfonic acid groups: evaluation of column
      performance with alkyl phenyl ketones and neutral moderately polar pesticides.
AB  - In this report, we describe the preparation of porous polyacrylamide-based
      monolithic columns via vinyl polymerization. These monoliths possess in their
      structures bonded dodecyl ligands and sulfonic acid groups. While the sulfonic
      acid groups are meant to support the electroosmotic flow (EOF) necessary for
      moving the mobile phase through the monolithic capillary, the dodecyl ligands are
      introduced to provide the nonpolar sites for chromatographic retention. However,
      incorporating the sulfonic acid groups in the monoliths does not only support the
      EOF but also exhibit hydrophilic interaction with moderately polar compounds such
      as urea herbicides and carbamates insecticides. Consequently, mixed-mode
      (reversed-phase/normal phase) retention behavior is observed with neutral and
      moderately polar pesticides. The amount of sulfonic acid group in the monolith
      can be conveniently adjusted by changing the amount of vinylsulfonic acid added
      to the polymerization reaction. Optimum EOF velocity and adequate chromatographic
      retention are obtained when 15% vinylsulfonic acid is added to the reaction
      mixture. Under these conditions, rapid separation and high plate counts reaching
      greater than 400000 plates/m are readily obtained.

PMID- 11519966
TI  - Histidine-functionalized silica and its copper complex as stationary phases for
      capillary electrochromatography.
AB  - A histidine-functionalized silica was prepared by covalent bonding of the
      functional groups to silane-treated silica gel. Conversion of functional groups
      was confirmed by infrared (IR) spectra, elemental analysis, and potentiometry.
      The functionality of the silica gel is 0.293 mmol g(-1). The coordination
      behavior of the histidine-functionalized silica was investigated by metal
      capacity and electron paramagnetic resonance (EPR). EPR measurements at different
      copper loadings were made. The results showed that the copper histidine complex
      might be distorted tetragonal. Both histidine-functionalized silica and its
      copper complex were employed as stationary phases for packed capillary
      electrochromatography (CEC). Electrical current was found helpful for evaluating
      the properties of frit construction and the stationary phase packing. Test
      samples include neutral compounds, inorganic anions and organic anions. Factors
      influencing the separation behavior have been studied. With copper-histidine
      functionalized silica under the condition of citrate buffer (10 mM, pH 4.0) and
      applied voltage of -20 kV, the separation of benzoic acid, D- and L-mandelic
      acid, phthalic acid and salicylic acid could be achieved within 12 min. The
      column efficiency for these acids was more than 1.2 x 10(5) plates m(-1), except
      salicylic acid.

PMID- 11519967
TI  - Enantioseparation of hydroxy acids on easy-to-prepare continuous beds for
      capillary electrochromatography.
AB  - This paper deals with the enantioseparation of hydroxy acids by ligand-exchange
      capillary electrochromatography. A chiral continuous bed was easily prepared by
      in situ polymerization of monomers, including an L-4-hydroxyproline derivative.
      This phase showed chiral recognition for several hydroxy acids, in addition to
      amino acids.

PMID- 11519968
TI  - Characterization and applications of etched chemically modified capillaries for
      open-tubular capillary electrochromatography.
AB  - In this article, the effects of the stationary phase, buffer pH, organic modifier
      type, organic modifier composition, applied voltage, and temperature on the
      migration of several synthetic peptides in etched chemically modified open
      tubular capillaries are discussed. With these solutes, migration is due to two
      effects: electrophoretic mobility and solute/bonded phase interactions. In
      addition, relative migration rates are evaluated for the peptide samples as a
      function of these experimental variables in order to determine which parameters
      might be useful for optimizing separations in open-tubular capillary
      electrochromatography (OTCEC). Some examples of synthetic peptide separations are
      presented where the sample contains a major component and several minor species,
      demonstrating how the resolution of these mixtures can be affected by the
      appropriate choice of experimental variables.

PMID- 11519969
TI  - Organization of the neuronal circuits in the central nervous system during
      development.
AB  - The human brain is a product of genetic instructions, cellular interactions and
      influences of innate activity and external stimulation. The formation of the
      neural tube and the patterning of the brain are determined by homeotic genes.
      After a prosencephalic phase with the formation of the hemispheres, the neurons
      prolipherate to number about 100 billion halfway through gestation. They also
      migrate to their final positions in an inside-outside fashion with the newly
      formed neurons at the outer layer of the cortex, followed by synaptogenesis,
      programmed cell death and organization of the neuronal circuits. This phase is
      probably determined not only by genes but also by innate activity, which for
      example has been detected in the foetal retina: "Cells that fire together wire
      together while those which don't won't". CONCLUSION: Development of the neuronal
      circuits in the CNS can be viewed as epigenetic. i.e. many different components
      must come together at the right time and place.

PMID- 11519970
TI  - Bilirubin production, breast-feeding and neonatal jaundice.

PMID- 11519971
TI  - Why does maternal smoke exposure increase the risk of sudden infant death
      syndrome?

PMID- 11519972
TI  - Breast-milk fortification.

PMID- 11519973
TI  - Iron-fortified and unfortified cow's milk: effects on iron intakes and iron
      status in young children.
AB  - Iron intakes and iron status were evaluated in 36 young Swedish children given
      either iron-fortified or unfortified cow's milk. All children had good iron
      status and had received breast milk or iron-fortified formulae during infancy.
      Twenty 1-y-old children were randomized to a diet with iron-fortified milk (7.0
      or 14.9 mg Fe l(-1) and 16 to a diet with unfortified milk. The iron intakes in
      the unfortified group at 15 and 18 mo (mean +/- SD 5.19 +/- 2.29 and 5.84 +/-
      1.62 mg d(-1)) were low in relation to Nordic Nutrition Recommendations, while
      the intakes in the iron-fortified group (10.20 +/- 2.60 and 10.87 +/- 2.79mg d(
      1)) were normal in relation to recommendations. The gain (increase) from
      receiving fortified diet during the study period was at most [upper limit for 95%
      confidence interval (CI)] 2.6 g l(-1) in blood haemoglobin, 1.9 fl in mean
      corpuscular volume, 2.7 micromol in serum iron and 4.5% in transferrin iron
      saturation, and the gain (decrease) was at most (lower limit for 95% CI) 0.29g l(
      1) in serum transferrin and 0.9mg l(-1) in serum transferrin receptor (TfR). None
      of these differences was statistically significant. There was an almost
      significantly higher increase in serum ferritin (1.4 times higher relation of
      values at the end compared with the beginning, p = 0.06) and a significantly
      higher (1.2; p = 0.047) decrease in TfR/ log10 ferritin ratio in the fortified
      group. CONCLUSION: One-year-old children starting out with good iron status given
      either iron-fortified or unfortified cow's milk from 12 to 18 mo maintain
      sufficient iron status during this period. However, children fed unfortified
      cow's milk have an iron intake which is low in relation to recommendations and
      the quantitative development of their reserve iron in iron stores seems to be
      weaker than that of the fortified group. The consequences of this require further
      study.

PMID- 11519974
TI  - Fifteen year trends in water intake in German children and adolescents: results
      of the DONALD Study. Dortmund Nutritional and Anthropometric Longitudinally
      Designed Study.
AB  - Water intake was evaluated and time trends in water intake and beverage
      consumption were assessed on the basis of 3 d weighed dietary records (n = 3,736)
      of 2-13-y-old males (n = 354) and females (n = 379) enrolled in the DONALD Study
      (Dortmund Nutritional and Anthropometric Longitudinally Designed Study, 1985
      1999). Total water intake increased with age from 1,114 g d(-1) in the 2-3-y-olds
      to 1,363 g d(-1) in the 4-8-y-olds and further to 1,801 g d(-1) (1,676 g d(-1))
      in the 9-13-y-old boys (girls); 33-38% came from food, 49-55% from beverages and
      12-13% from oxidation. Total water intake per body weight decreased with age from
      77.5 g kg(-1) (boys and girls) to 48.9 and 42.6 g kg(-1) in boys and girls,
      respectively. Milk (9-17%) and mineral water (12-15%) were the most important
      source of total water intake. In the 15 y period a significant increase in total
      water intake (+1.7 to +3.2 g MJ(-1) y(-1)) in all three age groups irrespective
      of sex was found. The increase of total water intake was mainly due to an
      increase in beverage consumption (+0.32 to +0.47% y(-1)). This study offers a
      differentiated insight into water intake and patterns of beverage consumption in
      German children and adolescents. CONCLUSION: The comparison of these data with
      other surveys points to a low total water intake, especially a low tap water
      intake, in German children and adolescents and underlines cultural influences on
      food and drinking habits.

PMID- 11519975
TI  - Early feeding resistance: a possible consequence of neonatal oro-oesophageal
      dyskinesia.
AB  - Paediatricians frequently find early feeding disorders in neonates and infants
      that result in poor weight gain and which sometimes have no clear organic basis.
      For many years, we have observed infants with unexplained poor feeding skills and
      excessive regurgitation, and since 1992 we have prospectively performed
      oesophageal manometry in infants hospitalized for retarded growth and
      "unexplained" feeding disorders. From the group of infants hospitalized for
      growth failure in the General Paediatric Unit of Necker-Enfants Malades Hospital
      from 1992 to 1997, we identified 16 children (3%) with abnormal feeding behaviour
      who had an abnormal oesophageal manometry. The manometric data of these children
      were compared with those of a group of 16 age-matched children who underwent
      oesophageal manometry for other reasons, and served as controls. The affected
      children had precocious feeding skills disorders: prolonged bottle-feeding (75%),
      bottle refusal (75%), unexplained crying (63%) and excessive regurgitation (94%).
      Half of them had mild anatomical facial consequences of their poor foetal
      sucking, and mild pharyngolaryngeal hypotonia, which could not be considered as
      malformations. Apart from these disorders, their clinical status was normal. At
      inclusion, their oesophageal manometry was abnormal, showing in 70% of cases
      specific anomalies: lower oesophageal sphincter hypertonia and/or partial failure
      to relax, and giant waves of oesophagus body. Their course was good and their
      feeding difficulties decreased around the end of the first year, with the
      acquisition of normal voluntary mastication. CONCLUSION: We suggest that the
      early feeding resistance of this group of children could be related to an organic
      and transient neonatal oro-oesophageal dyskinesia.

PMID- 11519976
TI  - Association between maternal pre-existing or gestational diabetes and health
      problems in children.
AB  - There is general consensus that children of women with pre-existing diabetes
      mellitus (PDM) have an increased risk of malformations and neurodevelopmental
      problems. Whether this is also true for children of women with gestational
      diabetes mellitus (GDM) is a matter of debate. This study investigated inpatient
      hospital care up to 10 y of age of children born to GDM and PDM women as a rough
      estimate of child morbidity. Hospital care of children born to 82,684 GDM women,
      3,874 PDM women and 1,213,957 controls was compared by linking the Swedish
      Medical Birth Registry with the Hospital Discharge Registry. Similar comparisons
      were performed in a local well-controlled group of 326 children born to GDM women
      in the Lund area. Children of PDM women and to a lesser degree children of GDM
      women had a statistically significant increase in hospitalizations, evident at
      least up to 10 y of age. Significantly increased risks of hospitalization were
      found for neurological/developmental disorders [odds ratio (OR) 2.30 and 1.36 for
      PDM and GDM, respectively)], malformations (OR 2.05 and 1.23), infections (OR
      1.56 and 1.20) and accidents (OR 1.32 and 1.14). CONCLUSION: The high
      hospitalization rates of these children indicate an increased morbidity,
      including neurodevelopmental disorders.

PMID- 11519977
TI  - Precocious puberty in children with tumours of the suprasellar and pineal areas:
      organic central precocious puberty.
AB  - During the past 11 y, 115 children younger than 8/9 y of age (female/male) with
      tumours of the suprasellar or pineal areas were followed in our clinic to study
      the incidence of precocious puberty. In addition, type of central lesion,
      clinical characteristics and gonadotropic secretion were studied in order to
      elucidate the different mechanisms of gonadal activation. A control group of 21
      patients with idiopathic precocious puberty and a control group of 10 age-matched
      patients with suprasellar tumours without precocious puberty were also studied.
      Precocious puberty associated with organic central lesions was found at diagnosis
      in 30 patients (26%), in 9 out of 48 patients with glial cell tumours (18.7%), 6
      out of 9 patients with germ cell tumours (66.6%), 11 out of 11 patients with
      hypothalamic hamartomas (100%) and in 4 out of 4 patients with subarachnoid cysts
      or arachnoidocele (100%). Precocious puberty was not found in any of 36 patients
      with craniopharyngioma. With the exception of one patient with pineal germinoma,
      all lesions were localized to the suprasellar area. In all patients with
      hypothalamic hamartoma, precocious puberty was diagnosed before 4 y of age, while
      in most patients with the other lesions, it was diagnosed after this age. Height
      SDS, weight increase and advancement of bone age were similar in both idiopathic
      and organic central precocious puberty. Maximal LH responses to GnRH in
      idiopathic and organic central precocious puberty were similar except for germ
      cell tumours. Patients with suprasellar tumours without precocious puberty had
      lower maximal LH (but not FSH) responses to GnRH, with the exception of germ cell
      tumours. In the latter, elevation of serum beta-hCG indicates that this
      gonadotropin was responsible for gonadal stimulation. In hypothalamic hamartomas,
      the prepubertal hiatus in the activity of the GnRH pulse generator was absent.
      The mechanism of this failure in the inactivation of GnRH is unknown. Data
      suggest that in glial cell tumours and in subarachnoid cysts, an unknown factor,
      probably secreted by the tumours, advances the tempo of GnRH maturation.
      Therefore, the aetiology of organic central precocious puberty is multiple and is
      directly related to location and type of lesion. CONCLUSION: This clinical
      information suggests that the onset of puberty is not the result of the
      disruption of a putative pulse generator inhibitory influence but the consequence
      of secretion of stimulatory substances by the lesions.

PMID- 11519978
TI  - Infantile genetic agranulocytosis, morbus Kostmann: presentation of six cases
      from the original "Kostmann family" and a review.
AB  - In 1956 Rolf Kostmann reported on six children with severe neutropenia associated
      with a block in myelopoiesis at the promyelocyte/myelocyte stage and an autosomal
      recessive inheritance. He named the new syndrome infantile genetic
      agranulocytosis. Today it is known as Kostmann's syndrome or severe congenital
      neutropenia. In 1975 an additional 10 cases from northern Sweden were published.
      This article reports on the only long-term survivor from the 1975 report plus
      another five patients born after 1975 who belong to the original "Kostmann
      family". Treatment and survival have changed dramatically since Kostmann's first
      publication. In the pre-antibiotic era, Kostmann's syndrome was inevitably fatal
      during the first year of life. CONCLUSION: Since the introduction of recombinant
      human granulocyte colony-stimulating factor (G-CSF) about 10 y ago, most patients
      now enjoy a normal life span and a greatly improved quality of life. Although the
      threat of death has disappeared, patients still have problems with infections,
      especially chronic gingivitis and periodontitis. In other groups of severe
      neutropenia, not related to the original "Kostmann family", an increased
      incidence of myeloid leukaemia has been observed. However, in this small cohort
      none of the children on chronic G-CSF therapy have developed malignancies.

PMID- 11519979
TI  - Danaparoid sodium (Orgaran) in four children with heparin-induced
      thrombocytopenia type II.
AB  - We report on four children with heparin-induced thrombocytopenia type II. In
      three patients, therapy with unfractionated heparin was associated with
      development of cardiac thrombi or with thrombosis progression up to the inferior
      vena cava or with aggravation of peripheral arterial occlusion. In the fourth
      child, the disease was recognized early on, and no complication occurred. Heparin
      induced thrombocytopenia type II was confirmed by heparin-induced platelet
      activation assay and/or heparin/platelet factor 4-ELISA. Concomitant elevated
      antiphospholipid antibodies were seen in all patients. Danaparoid sodium applied
      at a dosage of between 1.2 and 7.1 U/kg/h stopped the disease progression in each
      patient. Three children had a clinical recovery with partial recanalization, but
      for the child with peripheral arterial occlusion disease, amputation of some of
      the toes became necessary. CONCLUSION: Our data indicate that heparin-induced
      thrombocytopenia type II is a potential life-threatening disease in children and
      danaparoid sodium is beneficial in this age group.

PMID- 11519980
TI  - Breast milk from mothers of very low birthweight infants: variability in fat and
      protein content.
AB  - While breast milk appears to be superior to formula for the development of very
      low birthweight (VLBW) infants, it is supplemented to meet the metabolic demands
      of the rapidly growing premature infant. To estimate the nutritional variability
      of breast milk from mothers of VLBW infants, protein (bicinchoninic acid method)
      and fat content (creamatocrit) were measured in breast-milk spot samples from
      mothers of 20 VLBW infants, collected 4 times a day during the first 4 wk of
      lactation. Protein content (median 1.9 g dl(-1), range 1.1-3.5 g dl(-1)) and fat
      content (3.8/1.0-14.6 g dl(-1)) were highly variable and lacked a normal
      distribution over all samples and in individual women's milk. There was only a
      weak correlation between fat and protein (rs=0.416, p < 0.001). Fat but not
      protein was lower in morning samples than in samples collected later in the day
      (p < 0.001). Protein but not fat content decreased during the weeks of lactation
      (rs =-0.446, p < 0.001). No impact of the baby's gestational age was observed.
      CONCLUSION: The fat and protein content of breast milk from mothers of VLBW
      infants is highly variable, calling into question the clinical feasibility of
      individualized supplementation of breast milk for VLBW infants based on spot
      sample measurements.

PMID- 11519981
TI  - Serum bilirubin levels at 72 hours by selected characteristics in breastfed and
      formula-fed term infants delivered by cesarean section.
AB  - The present multicenter study analysed the relative impact of maternal and infant
      factors on serum bilirubin levels at 72 +/- 12 h in exclusively breastfed vs
      formula-fed term infants. End-tidal carbon monoxide levels corrected for ambient
      air (ETCOc), an index of bilirubin production, were measured in exclusively
      breastfed (B = 66) or formula-fed (F = 210) term infants at 2-8 h of age.
      Inclusion criteria included cesarean section to ensure a 3 d hospitalization,
      birthweight > or = 2,500 g, gestational age >37 wk and absence of any illness.
      The ETCOc for B infants and F infants did not differ significantly (1.3 +/- 0.7
      ppm vs 1.3 +/- 0.8 ppm). The serum bilirubin level at 72 +/- 12 h was
      significantly higher in B infants than in F infants (8.5 +/- 3.4mg dl(-1) vs 6.7
      +/- 3.4mg dl(-1) p < 0.001), as was the percentage weight loss from birthweight.
      Serum bilirubin levels were significantly higher in infants who were male, who
      did not have meconium-stained amniotic fluid, and in those whose mothers were
      insulin-dependent diabetics or hypertensive. There was no difference between
      groups in the need for phototherapy or exchange transfusion. CONCLUSION: Although
      higher bilirubin levels were observed in group B at 72 +/- 12 h compared with
      group F, this finding was not of clinical or therapeutic consequence in this
      study. The lack of difference in ETCOc between the groups may be a factor of the
      timing of ETCOc measurement in this study, or may suggest that early increased
      bilirubin production is not a significant contributor to jaundice observed in
      exclusively breastfed infants. Key words: bilirubin, breastfeeding, jaundice

PMID- 11519982
TI  - Spectrum of outcome in infants with extreme neonatal jaundice.
AB  - The increasing number of case reports on neurologic sequelae related to
      hyperbilirubinaemia may represent a re-emergence of kernicterus in the
      industrialized world. However, not much has been written about infants who
      survived extreme levels of serum bilirubin without neurologic damage. We present
      three cases of extreme neonatal hyperbilirubinaemia, all with peak serum
      bilirubin levels >600 micromol/L. Two of the infants developed neurologic
      sequelae, but the third infant did not. In contrast to the two with sequelae, the
      infant without sequelae was female, had a positive Coombs' test, less clinical
      signs compatible with bilirubin encephalopathy, and a shorter exposure to serum
      bilirubin values >400 micromol/L. CONCLUSION: The basic mechanism of bilirubin
      neurotoxicity remains unknown, and it is not clear why some infants do not
      develop neurologic injury at serum bilirubin levels at which others do. We
      speculate that a comparison between patients with sequelae and those without may
      yield important information.

PMID- 11519983
TI  - Arterial air embolism after venous air infusion in newborn piglets.
AB  - In the newborn period, decreased right atrial pressure results in functional
      closure of the foramen ovale (FO). The objective of this study was to investigate
      whether air bubbles infused in the vena cava will pass through the FO into the
      arterial circulation in a newborn animal. Since air tends to rise to the highest
      point in a fluid, the study also investigated whether the animal's position could
      influence arterialization of air. Twelve 1-3-d-old piglets were anaesthetized and
      mechanically ventilated, and had catheters placed in the vena cava for infusion
      of air, in the aorta for blood gas and blood pressure measurements, and in the
      pulmonary artery for pressure measurements. After stabilization, 0.05 ml kg(-1)
      per minute of air was infused for 25 min followed by a 3 h observation period.
      Six piglets were placed in the left, and six in the right lateral recumbent
      position. Air bubbles in the left atrium or ventricle was monitored by
      echocardiography. Ultrasound Doppler probes were placed on both carotid arteries
      for detection of air embolism. Gas bubbles were detected in the left ventricle
      within 45 s of air infusion in 11 of 12 piglets. Eight piglets had air bubbles in
      the carotid arteries. Mean pulmonary arterial pressure (PAP) increased
      significantly after 1 min of air infusion, whereas mean systemic arterial
      pressure remained unchanged. When arterial air embolism occurred, PAP had not
      increased significantly. The time to reach maximum PAP with the animals in the
      left recumbent position was significantly shorter than in the right. CONCLUSION:
      This study shows that venous gas bubbles enter the arterial circulation through
      the FO in newborn piglets and that body position may influence the haemodynamic
      effect of these bubbles.

PMID- 11519984
TI  - Ventilatory responses to rebreathing in infants exposed to maternal smoking.
AB  - This study assessed the effect of maternal smoking during pregnancy on
      ventilatory and waking responses of infants to a respiratory challenge. This
      challenge mimicked the time-course and concentration of gases that an infant
      would experience rebreathing face-down into soft bedding. Control (C; n = 97) and
      smokers' infants (SM; n = 96) were studied at ages I and 3 mo. Asphyxial gas
      (hypercapnia/hypoxia) was delivered to the supine sleeping baby via a hood by
      slowly altering the inspired air: CO2 maximum 5% and O2 minimum 13.5%.
      Respiratory pattern was recorded by inductive plethysmography as the sum of
      ribcage and abdominal movements. The change in ventilation with inspired CO2 was
      measured over 5-6 min of the test. The slope of a linear curve fit relating
      inspired CO2 to the logarithm of ventilation was taken as a quantitative measure
      of ventilatory asphyxial sensitivity (VAS). Protective responses were graded from
      1: no waking and an estimated arterial carbon dioxide tension (PaCO2) > or = 60
      mmHg (least protective), to 4: fully awake (most protective). The results showed
      VAS was higher in SM infants than controls: +0.03 (p = 0.04). The oxygen
      saturation (SaO2) of SM infants fell -0.4% (p = 0.02) more than SaO2 of controls
      despite a greater tidal volume increase: +13.0% (p = 0.04). Overall protective
      responses were the same between groups, but grade 1, although rare, was found in
      7 SM infants and only 4 control infants; this difference was not significant.
      CONCLUSION: The study did not confirm the postulate that infants of mothers who
      smoked during pregnancy have a reduced ventilatory response or raised waking
      thresholds.

PMID- 11519985
TI  - Levels of certain metals, organochlorine pesticides and dioxins in cord blood,
      maternal blood, human milk and some commonly used nutrients in the surroundings
      of the Aral Sea (Karakalpakstan, Republic of Uzbekistan).
AB  - Since the 1960s a massive decline in the volume of the Aral Sea has occurred as a
      result of the diversion of the supplying rivers to cotton irrigation schemes. The
      contaminated sediment of the former seabed has been disseminated over the
      surrounding area by strong winds. This deterioration of the ecosystem has created
      a hazardous situation for the health of approximately 3.5 million people. This
      pilot study was undertaken to assist Karakalpak health workers in investigating
      the degree of exposure to metals, persistent organochlorine pesticides (OCPs) and
      dioxins during the most vulnerable prenatal and postnatal period and to provide
      guidelines for future research. All subjects came from areas located within 200
      km of the southern border of the Aral Sea. Blood was obtained from 18 pregnant
      women and 28 newborns (cord blood) to determine the levels of metals, lead,
      cadmium, zinc and selenium and the OCPs alpha-, beta- and gamma
      hexachlorocyclohexane (HCH; lindane is the product name of gamma
      hexachlorocyclohexane), hexachlorobenzene (HCB), and isomers and metabolites of
      dichlorodiphenyltrichloroethane (DDT), i.e. op-DDT, pp-DDT, pp-DDE and pp-TDE.
      Levels of metals were also determined in blood from 28 non-pregnant women. In
      addition, levels of 17 dioxins were determined in 41 human milk samples and
      1batch of formula. Information about possible dietary sources of the fat-soluble
      OCPs and dioxins was obtained from a pooled sample of butter and from seven
      cottonseed oil samples. A mass-selective detector coupled to a gas chromatograph
      equipped with a large volume injector was used to analyse the selected OCPs,
      whereas the dioxins were determined by gas chromatography with high-resolution
      mass spectrometry. The levels of metals in cord and maternal blood were
      consistent with concentrations observed in European countries. Only three women
      (7%) had lead levels greater than 100 ppb. The most notable pollutants in
      maternal and cord blood were the OCPs, notably HCB, beta-HCH, pp-DDE and the most
      toxic dioxin, 2,3,7,8-TCDD, when calculated as TEQs. A similar pattern was
      observed in human milk: beta-HCH and pp-DDE levels of more than 1,000 ng g(-1)
      fat were found in 68 and 43% of the subjects, respectively. Levels of 2,3,7,8
      TCDD were six times higher than those observed in Western Europe. Traces of pp
      DDE were detected in the batch of formula milk. Contaminated animal fat, but not
      cottonseed oil, is the most likely dietary source of OCPs and dioxins.
      CONCLUSION: Further epidemiological research is needed to elucidate the health
      implications of these pollutants on perinatal and maternal health, including
      lactation. More importantly, an investigation should be initiated to identify the
      emission sources of persistent organic pollutants in Karakalpakstan and adjacent
      regions.

PMID- 11519986
TI  - Childhood acute rheumatic fever in Greece: experience of the past 18 years.
AB  - This study reports on the authors' experience with acute rheumatic fever (ARF)
      during the years 1980-1997. The objectives were to estimate the incidence of the
      disease an area of Greece to characterize its epidemiology, to determine the
      frequency of the antecedent symptoms and to describe its clinical presentation.
      The medical records of 66 confirmed cases admitted to the First Department of
      Pediatrics, "Aghia Sophia" Children's Hospital, were reviewed. Two outbreaks
      occurred during this period. In contrast to the 3-4 cases seen every year, 14
      cases were diagnosed during the 6 mo period from October 1989 to March 1990. An
      additional 10 cases were diagnosed in 1993. Most of the children (76%) were
      between 8 and 14 y old. The children were predominantly from middle-class
      families with ready access to medical care. Carditis, evident by auscultation,
      and arthritis were the dominant major manifestations in 70% and 68% of the cases,
      respectively. Mild carditis was present in 54% of children with valvular disease.
      CONCLUSION: ARF exists in the paediatric Greek population with exacerbations and
      remissions, but the cardiac manifestations appear mild or moderate.

PMID- 11519987
TI  - Vitamin C is reduced in human milk after storage.
AB  - In order to establish how cold storage of human milk affects levels of
      bioavailable vitamin C, 11 samples were stored for 24 h in the refrigerator or up
      to 2 mo in the freezer. Total vitamin C levels decreased on average by one-third
      in the refrigerator or after I mo of freezing, with wide variations between
      individuals (6 to 76% and 3 to 100%, respectively). After 2 mo of freezing, the
      average decrease was two-thirds (7-100%). CONCLUSION: We recommend a change in
      human milk storage practices, to under 24 h in a refrigerator or under 1 mo in a
      freezer. Alternatively, vitamin C supplementation may be considered.

PMID- 11519988
TI  - Transcutaneous-PO2 monitoring for detection of exercise-induced right-to-left
      shunts in children with congenital heart defects: a case report.
AB  - A 2-y-old boy with scimitar syndrome underwent surgery involving the redirection
      of partial anomalous pulmonary venous return to the left atrium. Heart
      catheterization after the operation did not reveal any significant intra-cardiac
      shunts. An exercise test performed at the age of 10 y revealed a reduction in
      working capacity. At the age of 12 y, the patient became unconscious and
      experienced seizures during heavy physical exercise. EEG and Holter ECG
      examinations were normal. In a second exercise test, a fall in transcutaneous PO2
      was demonstrated at the start of the test. A new heart catheterization revealed
      communication between the inferior vena cava and the left atrium owing to a
      misplaced patch. No right-to-left shunt was found at rest, probably as a result
      of drainage of the inferior vena cava to the superior vena cava by the azygous
      vein. An exercise test after re-operation revealed normal conditions. CONCLUSION:
      Haemodynamic studies during heart catheterization in children are usually
      performed at rest. This could result in exercise-induced right-to-left-shunts
      being overlooked. The use of PtcO2 monitoring during exercise tests is a non
      invasive means of exposing these shunts.

PMID- 11519989
TI  - Peripheral blood cells with expression of the interleukin-2 receptor (CD25+) in
      severely infected full-term neonates.

PMID- 11519990
TI  - Benign lymphoproliferation syndrome, autoimmune neutropenia and thrombocytopenia
      in partial Di George syndrome: efficacy of rh G-CSF and prednisone.

PMID- 11519991
TI  - High prevalence of genotypic zidovudine resistance among HIV-infected Canadian
      children.

PMID- 11519992
TI  - Low doses of recombinant erythropoietin in the treatment of anaemia of
      prematurity.

PMID- 11519993
TI  - External chest compression for the treatment of a mechanically ventilated child
      with status asthmaticus.

PMID- 11519994
TI  - 5-Oxoprolinuria: a cause of neonatal metabolic acidosis.

PMID- 11519995
TI  - Cerebrotendinous xanthomatosis presenting as "chologenic diarrhoea".

PMID- 11519996
TI  - Potential application of catalase-peroxidase from Comamonas terrigena N3H in the
      biodegradation of phenolic compounds.
AB  - Comamonas terrigena N3H is a gram-negative rod-shaped bacterium that was isolated
      from contaminated soil in Slovakia. This bacterium showed remarkable
      biodegradation properties. We investigated the expression and functioning of two
      catalase isozymes in this bacterium. The typical catalase could be induced by
      cadmium ions, whereas the catalase-peroxidase enzyme was constitutively
      expressed. Since C. terrigena lacks the key enzyme for complete degradation of
      phenols (phenolhydroxylase), we analysed the possible removal of phenol by the
      two catalases of this bacterium. Addition of phenol to the culture medium led to
      increased expression of the catalase-peroxidase. Applying oxidative stress prior
      to phenol administration markedly induced the expression of the typical catalase,
      irrespective of the nature of the added agent. Thus, the rate of phenol
      degradation is rather reduced under these conditions, while growth of the cells
      is not impaired. We concluded that phenol peroxidation in C. terrigena can be
      largely attributed to the action of a catalase-peroxidase. The potential
      application of this enzyme in the removal of phenol from the environment is
      discussed.

PMID- 11519997
TI  - Characterization of Rhizobium loti strains from the Salado River Basin.
AB  - Thirty indigenous rhizobia strains, isolated from Lotus tenuis in the area of
      Chascomus and other regions of the Salado River Basin (Argentina), were
      characterized based on generation time, acid production, carbon utilization,
      protein profile, and molecular characterization by restriction fragment length
      polymorphism (RFLP) analysis of 16S rRNA genes amplified by the polymerase chain
      reaction (PCR). The results indicated that native rhizobia isolates from the
      Chascomus area are predominantly fast and intermediate-growers. The unclassified
      rhizobia examined by PCR-RFLP were found to be closely related to the reference
      strains of validly described Rhizobium species.

PMID- 11519998
TI  - Phylogeny of Streptomyces species and evidence for horizontal transfer of entire
      and partial antibiotic gene clusters.
AB  - The phylogenetic relationships of a collection of streptomycete soil isolates and
      type strains were resolved by sequence analysis of trpB, a housekeeping gene
      involved in tryptophan biosynthesis. The analysis confirmed that two isolates
      were recipients in a gene transfer event, demonstrated by phylogenetic
      incongruency between trpB and strB1 trees. One strain had acquired the entire
      streptomycin biosynthetic cluster, whilst the other contained only strRAB1, the
      resistance gene and two flanking genes from the cluster. Sequence analysis of
      trpB, as part of a polyphasic approach, was a useful tool in determining intra
      generic relationships within the genus Streptomyces.

PMID- 11519999
TI  - Evolution of catabolic pathways and metabolic versatility in Pseudomonas stutzeri
      OX1.
AB  - Pseudomonas stutzeri OX1 is able to degrade toluene and ortho-xylene via the
      direct oxygenation of the aromatic ring. The genetic studies carried out suggest
      that the genes coding for the monooxygenase involved in the early steps of this
      catabolic route have been acquired by gene transfer. P stutzeri OX1 is also
      potentially able to utilize meta- and para-xylene as growth substrates. These two
      isomers are metabolized through a different pathway (TOL pathway). Both catabolic
      routes can be activated or inactivated by means of genomic rearrangements. The
      relevance of such recombination mechanisms in the evolution and the adaptability
      of P. stutzeri is discussed.

PMID- 11520000
TI  - Environmental bacteriophage-host interactions: factors contribution to natural
      transduction.
AB  - Over the past two decades the potential for the exchange of bacterial genes in
      natural environments through transduction (bacteriophage-mediated gene transfer)
      has been well established. Studies carried out by various laboratories throughout
      the world have demonstrated that both chromosomal and plasmid DNA can be
      successfully transduced in natural environments ranging from sewer plants to
      rivers and lakes. Transduction has been shown to take place in the gills of
      oysters and the kidneys of mice. Model studies have demonstrated the ability of
      transduction to maintain genetic material in bacterial gene pools that would
      otherwise be lost because of negative fitness. Thus, transduction may affect the
      course of bacterial evolution. Identification of natural transduction has led to
      the investigation of the dynamics of bacteriophage host interactions in natural
      aquatic environments and to the exploration of various environmental factors that
      affect virus-host interactions. Two important environmental factors which affect
      virus-host interactions are the metabolic state of the host and the exposure of
      the host to DNA-damaging stresses such as solar UV light. Recent researches on
      these two areas of virus-host relationships are reviewed.

PMID- 11520001
TI  - Bacterial diversity in soil samples from two uranium waste piles as determined by
      rep-APD, RISA and 16S rDNA retrieval.
AB  - The bacterial diversity in two uranium waste piles was studied. Total DNA was
      recovered from a large number of soil samples collected from different sites and
      depths in the piles using two procedures for direct lysis. Significant
      differences in the bacterial composition of the samples were revealed by the use
      of rep-APD, RISA and 16S ARDREA. The 16S rDNA analyses showed that the uranium
      wastes were dominated by Acidithiobacillusferrooxidans and by several Pseudomonas
      species classified in the gamma-subdivision of the Proteobacteria. The three
      kinds of A. ferrooxidans 16S and IGS rDNA specific fragments that were found
      corresponded to the three phylogenetic groups recognised in this species. This
      microdiversity probably reflects the genetic adaptation of the uranium waste
      strains to different concentrations of heavy metals.

PMID- 11520002
TI  - Sequence analysis and insertional inactivation of a gene encoding Moraxella sp.
      CK-1 cell wall hydrolase.
AB  - Sequencing of the Moraxella sp. CK-1 autolysin (cell wall hydrolases) gene showed
      the presence of an open reading frame which encodes a polypeptide of 273 amino
      acids with a molecular mass of 33,316 Da. A presumed ribosomal binding site, a
      possible -10 and -35 region, and rho-dependent terminators were found. The C
      terminal region of the mature protein showed considerable homology with the
      Thermus sp. serine proteinase. Enzyme assay suggests that the recombinant
      autolysin has amidase or endopeptidase activity. Analysis of the peptidoglycan
      fragments, following the treatment with the autolysin, indicates that this
      protein is an N-acetylmuramyl-L-alanine amidase. Insertional inactivation of the
      autolysin of Moraxella sp. CK-1 chromosome led to a decrease in cell wall
      hydrolytic activity, clumping of the cells, and color change. No lytic band
      present in inactivated magA mutant by renaturing SDS-PAGE.

PMID- 11520003
TI  - A relationship between RP4 plasmid acquisition and phenotypic changes in
      Pseudomonas fluorescens R2fN.
AB  - The physiological behaviour of Pseudomonas fluorescens strain R2fN was compared
      to that of transconjugants [R2fN(RP4)], and two aggregation phenotypes were
      identified (Agr- and Agr+). Agr+ phenotype is characterized by the appearance of
      macroscopic aggregates when cells are growing in liquid media. Transconjugants
      exhibited Agr+ phenotype whereas wild type strain represented Agr-. Evidence is
      presented to support correlation between Agr+ phenotype acquisition and the
      presence of the broad-host range plasmid RP4 in strain R2fN. In addition,
      according to bacterial adherence to hydrocarbon test the transconjugant cells
      appeared to be very hydrophilic whereas wild type R2fN cells were hydrophobic.

PMID- 11520004
TI  - A comparison of ammonia-oxidiser populations in eutrophic and oligotrophic basins
      of a large freshwater lake.
AB  - A combination of PCR amplification and oligonucleotide probing was used to
      investigate the populations of ammonia-oxidisers of the beta-Proteobacteria in
      the eutrophic and oligotrophic basins of Lake Windermere, a large temperate lake
      in the English Lake District. Numbers of ammonia-oxidisers (MPN) in the
      Windermere lakewater were low (< 100 cells ml(-1)) throughout the year with the
      exception of peaks in August, which coincided with stratification, and November
      in the South Basin where overturn may have introduced ammonia-oxidising bacteria
      into the water column. Sediment samples contained larger populations of ammonia
      oxidisers, usually ca. 10(4) per g. dry weight, which remained relatively
      constant throughout the seasonal cycle in both Basins. DNA was recovered from
      lakewater and sediment samples and Nitrosospira and N. europaea-eutropha lineage
      16S rRNA genes amplified in a nested PCR reaction, with confirmation of identity
      by oligonucleotide hybridisation. Nitrosospira 16S rDNA was readily detected in
      all samples and therefore found to be ubiquitous. In contrast, nitrosomonad DNA
      of the N. europaea-eutropha lineage could only be detected in the oligotrophic
      North Basin. Enrichment cultures of lakewater samples only exhibited
      nitrification at low (0.67 mM) and medium (5 mM) ammonium concentrations, whilst
      sediment enrichments nitrified at all concentrations tested including high (12.5
      mM) ammonium medium. These data suggest that ammonia-oxidiser populations may be
      physiologically distinguished between lakewater and sediment, and that species
      distribution in a single lake is non-uniform.

PMID- 11520005
TI  - Characterization of two novel Rhizobium leguminosarum bacteriophages from a field
      release site of genetically-modified rhizobia.
AB  - Two Rhizobium leguminosarum biovar viceae bacteriophages with contrasting
      properties were isolated from a field site in which the survival of genetically
      modified R. leguminosarum inoculants had been monitored for several years.
      Inoculant strain RSM2004 was used as the indicator for phage isolation and
      propagation. One phage, RL1RES, was temperate and could not replicate in any of
      the 42 indigenous R. leguminosarum field isolates tested although nested PCR
      indicated that phage sequences were present in six of the isolates. The second
      phage, RL2RES, was virulent, capable of generalised transduction, contained DNA
      with modified cytosine residues, and was capable of infecting all field isolates
      tested although the GM inoculant strain CT0370 was resistant. Sequence with
      homology to RL2RES was detected by nested PCR in six of the 42 field-isolates.
      These were not the same isolates that showed homology to RL1RES. The implication
      of these findings for the survival of rhizobial inoculants, and the ecology of
      phages and their host bacteria, are discussed.

PMID- 11520006
TI  - Comparison of yoghurt, heat treated yoghurt, milk and lactose effects on plasmid
      dissemination in gnotobiotic mice.
AB  - The effect of yoghurt, heat-treated fermented milk, milk and lactose solution
      intake on plasmid transfer and establishment of the resulting transconjugants in
      the digestive tract of mice colonised with human faecal flora were examined.
      Yoghurt lowered the population level of transconjugants more efficiently than
      heat-treated fermented milk (-2 log and -1 log respectively) and indicated a
      beneficial effect of viable bacteria. On the other hand consumption of milk
      drastically inhibited the establishment of transconjugants, which were below the
      detection threshold of 10(2) UFC per g of faeces. We were not able to recover
      transconjugants from faecal samples with lactose supplementation, indicating a
      possible inhibition of plasmid transfer. Since the yoghurt, heat-treated
      fermented milk, milk and lactose solution contained approximately the same
      lactose concentration it is fair to speculate that lactose may contribute to the
      inhibiting effects of the various supplementations. The inhibitions described
      were not associated with other intestinal parameters like the intestinal transit
      time, the population levels of the recipient, or the donor and total anaerobic
      microflora. It is evident that other parameters need to be investigated such as
      the composition of the endogenous microflora and metabolic products.

PMID- 11520007
TI  - Methanotrophic diversity in an agricultural soil as evaluated by denaturing
      gradient gel electrophoresis profiles of pmoA, mxaF and 16S rDNA sequences.
AB  - Molecular methods were used to characterize the diversity of a methanotrophic
      population in an agricultural soil. For this purpose we have used DGGE analysis
      of functional and phylogenetic markers. Functional markers utilised comprised the
      pmoA-gene coding for the alpha-subunit of the particulate methane monooxygenase
      (pMMO) present in all known methanotrophs and the mxaF-gene coding for the alpha
      subunit of methanol dehydrogenase (MDH) present in all gram-negative
      methylotrophs. In addition, we have used 16S rDNA as a phylogenetic marker. DGGE
      patterns of an enrichment culture, and sequencing of major DGGE bands obtained
      with the bacterial specific primers showed that the community structure was
      dominated by methanotrophic populations related to Methylobacter sp. and
      Methylomicrobium sp. The PCR products amplified with the functional primer sets
      were related to both type I and type II methanotrophs. We also designed a new
      pmoA-targeting primer set which could be used in a nested protocol to amplify PCR
      products from DNA extracted directly from the soil.

PMID- 11520008
TI  - Towards effective treatment of eating disorders: nothing is as practical as a
      good theory.
AB  - There is much room for improvement in the treatment of eating disorders, anorexia
      nervosa in particular. It is argued that for more effective treatment a radical
      change in thinking and doing is needed. First, the wide-spread multicausal model
      of eating disorders must be abandoned and replaced by (a) fundamental strategic
      research into the most parsimonious explanation of eating disorders and (b)
      interventions solely directed on the specific maintaining mechanisms. Second,
      evidence-based working is needed in mental health care. In daily practice, two of
      three psychotherapists do not treat their eating disordered patients with the
      best treatment available, i.e. cognitive behaviour therapy. The Dutch Ministry of
      Health, Welfare and Sport tried to improve the care for eating disorder patients
      by the nomination of several specialist hospital units. These units are, however,
      not selected for their treatment quality or the use of evidence-based treatment
      protocols. It is argued that this ministerial operation will not increase the
      supply of effective treatment. The Minister obviously should have done two other
      things to improve the amount and quality of treatment supply for eating
      disorders: First, she better could invest in a broad array of workshops, training
      and supervision programs in cognitive behaviour therapy for all psychotherapists
      working with eating disorders. Second, since nothing is so practical as a good
      theory, the facilitation of research into parsimonious models of the relevant
      mechanisms as well as the experimental tests of interventions on these mechanisms
      would have been a promising move to effective treatment.

PMID- 11520009
TI  - The contribution of thought-action fusion and thought suppression in the
      development of obsession-like intrusions in normal participants.
AB  - Both thought-action fusion (TAF: i.e., a cognitive bias implying an inflated
      sense of responsibility for one's own thoughts) and thought suppression have been
      claimed to contribute to the development of obsession-like intrusions. Therefore,
      it seems plausible that conjunction of these phenomena results in highly intense
      intrusions. However, possible interactions between TAF and thought suppression
      have not yet been investigated experimentally. In the current study, healthy
      volunteers were exposed to a TAF-like intrusion. They were, then, randomly
      assigned to a suppression (n=21) or non-suppression condition (n=19). Next,
      visual analogue scales (VASs) were completed measuring anxiety, feelings of
      responsibility and guilt, urge to neutralise and so on. Contrary to expectation,
      several VAS scores were lower for participants in the suppression group than for
      those in the non-suppression group. Hence, it is concluded that thought
      suppression may, at least in the short term, alleviate discomfort caused by TAF
      like intrusions.

PMID- 11520010
TI  - Repeated exposure of flight phobics to flights in virtual reality.
AB  - The present study examined the effects of repeated exposure of flight phobics to
      flights in virtual reality (VR). Flight phobics were randomly assigned either to
      complete one VR test flight followed by four VR exposure flights (VR group; N=15)
      in one lengthy session or to complete one VR test flight followed by a lengthy
      relaxation training session (relaxation group; N=15). All participants completed
      a second VR test flight at the end of the session. Fear reports and physiological
      fear reactions (heart rate, skin conductance level) during VR exposures were
      registered, and fear of flying was assessed psychometrically from 3 weeks before
      to 3 months after exposure. Exposure to VR flights elicited subjective and
      physiological fear responses in flight phobics, and these responses attenuated
      within and across VR flights. Fear reduction associated with repeated VR exposure
      was greater than fear reduction caused by relaxation training. Fear of flying
      improved in both treatment groups, but several outcome measures indicated greater
      effects in the VR treated group than in the relaxation group. These findings
      indicate that exposure in virtual reality may offer a new and promising approach
      for the treatment of fear of flying.

PMID- 11520011
TI  - Anxiety and depression as correlates of self-reported behavioural inhibition in
      normal adolescents.
AB  - In a previous study, Muris, Merckelbach, Wessel, and Van de Ven
      [Psychopathological correlates of self-reported behavioural inhibition in normal
      children. Behav. Res. Ther. 37 (1999) 575-584] found that children who defined
      themselves as high on behavioural inhibition displayed elevated levels of
      psychopathological symptoms compared to children who defined themselves as low or
      middle on behavioural inhibition. The present study further examined the
      relationship between self-reported behavioural inhibition and anxiety disorders
      and depression symptoms in a large sample of adolescents aged 12-18 years
      (N=968). Adolescents completed a measure of behavioural inhibition and
      questionnaires of anxiety and depression. Results indicated that adolescents who
      classified themselves as high on behavioural inhibition had higher scores of
      anxiety and depression than adolescents who classified themselves as low or
      middle on behavioural inhibition. Structural equations modelling was employed to
      test hypothetical models on the role of behavioural inhibition in childhood
      anxiety and depression. It was found that a pathway in which behavioural
      inhibition results in anxiety, which in turn leads to depression, provided the
      best fit for the data.

PMID- 11520012
TI  - A prospective investigation of the role of cognitive factors in persistent
      posttraumatic stress disorder (PTSD) after physical or sexual assault.
AB  - The effectiveness of psychological treatments for PTSD is likely to be enhanced
      by improved understanding of the factors involved in maintaining the disorder.
      Ehlers and Clark [A cognitive model of persistent posttraumatic stem disorder
      Behav. Res. Ther. 38 (2000) 319-345] recently proposed a cognitive model of
      maintenance. The current study aimed to investigate several cognitive factors
      highlighted in Ehlers and Clark's model using a prospective design. Fifty-seven
      victims of physical or sexual assault participated in the study. Cognitive
      factors were assessed within 4 months of assault and victims were followed-up 6
      and 9 months after the assault. Cognitive variables which significantly predicted
      PTSD severity at both follow-ups were: cognitive processing style during assault
      (mental defeat, mental confusion, detachment); appraisal of assault sequelae
      (appraisal of symptoms, perceived negative responses of others, permanent
      change); negative beliefs about self and world; and maladaptive control
      strategies (avoidance/safety seeking). Relationships between early appraisals,
      control strategies, and processing styles and subsequent PTSD severity remained
      significant after statistically controlling for gender and perceived assault
      severity. These findings support the cognitive model of PTSD proposed by Ehlers
      and Clark and suggest that effective treatment will need to address these
      cognitive factors.

PMID- 11520013
TI  - The impact of behavior-specific and behavior-nonspecific reinforcement on child
      compliance to mother directives.
AB  - Theories of child socialization differ with regard to the influence they
      attribute to behavior-specific reinforcement contingencies versus behavior
      nonspecific reinforcement contingencies (i.e. social responsiveness). The present
      research investigated, at a within-individual level, the relationship between
      both types of reinforcement and child compliance with maternal directives.
      Behavior-specific reinforcement was defined as the history of reinforcement
      obtained by children for prior episodes of compliance and noncompliance to mother
      directives. Behavior-nonspecific reinforcement was defined as the history of
      reinforcement obtained by children for prosocial and aversive behaviors unrelated
      to mother directives. It was hypothesized that both reinforcement processes would
      be related to child responses to subsequent mother directives. The findings
      support these hypotheses. The discussion addresses caretaker social
      responsiveness as an intervention target of behavioral family therapy.

PMID- 11520014
TI  - Harmful dysfunction and the search for value neutrality in the definition of
      mental disorder: response to Wakefield, part 2.
AB  - Wakefield's claims to have identified and objective scientific component of
      mental disorders in the concept of dysfunction are examined in light of previous
      attempts to state a value free concept of mental disorders. The harmful
      dysfunction concept of dysfunction is not value free because it confounds cause
      and purpose in a specious use of evolutionary theory and because evolutionary
      theory cannot reliably supply standards for when a function is broken. Harmful
      dysfunction analysis collapses into a value-laden concept of mental disorders and
      serves the untoward goal of promoting the status quo in the modern DSMs. If the
      concept of dysfunction were taken seriously and rigorously defined, then it might
      be possible to separate what is medical from what is not in the domain of mental
      disorders.

PMID- 11520015
TI  - Rapidly progressing hip disease.

PMID- 11520016
TI  - Rapidly progressing hip disease.

PMID- 11520017
TI  - Factors affecting the outcome of total shoulder arthroplasty.
AB  - Total shoulder arthroplasty (TSA) has become the treatment of choice for most
      glenohumeral arthritides. Results are variable and depend on many factors,
      including normal and prosthetic anatomy and biomechanics, surgical technique,
      rotator-cuff integrity, bone deficiency, and postoperative rehabilitation. In
      this article, we discuss these factors and their influence on achieving
      successful TSAs.

PMID- 11520018
TI  - Contemporary issues in total hip arthroplasty.

PMID- 11520019
TI  - Posterior lumbar interbody cages do not augment segmental biomechanical
      stability.
AB  - The effect on stiffness of installing posterior threaded interbody cages at LA-L5
      was evaluated using fresh human cadaveric spine specimens. The cages did not
      increase spine stiffness significantly in any tested range of motion.
      Supplemental posterior pedicular screw/rod instrumentation, however,
      significantly increased stiffness. The assertion that use of cages as isolated
      posterior implants improves stability may be invalid.

PMID- 11520020
TI  - Efficacy of nonoperative treatment for lateral epicondylitis.
AB  - One hundred cases of lateral epicondylitis among 97 patients were reviewed, and
      84 patients were contacted for long-term follow-up. Patients participated in a
      structured nonoperative treatment regimen. Mean age of contacted patients was 49
      years; mean follow-up was 2.8 years. Surgery was averted in 65 (75%) of 87 cases.
      Patients who achieved pain control after only 1 cortisone injection successfully
      avoided surgery 88% of the time, whereas those requiring multiple injections
      avoided surgery only 44% of the time. Eventual outcomes were similar, regardless
      of treatment type. Patients requiring multiple cortisone injections to alleviate
      acute pain have a guarded prognosis for continued nonoperative management.

PMID- 11520021
TI  - Chondrolysis and joint destruction secondary to snake envenomation.
AB  - Although snakebite injuries to the hand are common, intra-articular envenomation
      has rarely been reported. In this article, we describe a patient who was bitten
      by a rattlesnake and whose left-index-finger distal interphalangeal joint
      sustained intra-articular envenomation that resulted in aseptic chondrolysis and
      severe joint destruction 1.5 years later. Multiple cultures and biopsies were
      negative, and histology was consistent with nonspecific degenerative changes
      secondary to necrosis of the articular cartilage from retained toxins. The
      patient chose arthrodesis; 24 months postoperatively, he was pain-free and had
      returned to work.

PMID- 11520022
TI  - Complete median nerve transection as a complication of carpal tunnel release with
      a carpal tunnel tome.
AB  - A 48 year-old right-hand-dominant man presented to our institution with
      paresthesia and loss of feeling along the median nerve distribution of the right
      hand 1 week after undergoing minimally open carpal tunnel release with the Biomet
      Indiana Tome at another hospital. At surgery, transection of the median nerve was
      discovered and repaired. This is the first report of a complete median nerve
      transection using the revised carpal tunnel tome with a single-pass technique.

PMID- 11520023
TI  - Familial torticollis with polydactyly: manifestation in three generations.
AB  - Familial transmission of congenital muscular torticollis (CMT) has been reported
      in the literature, and postaxial polydactyly has been frequently reported in
      familial cases, but, to our knowledge, familial CMT with postaxial polydactyly
      has not been described. In this article, we report a rare case of CMT with
      postaxial polydactyly in 3 generations of a family and suggest an autosomal
      dominant pattern of inheritance in these cases.

PMID- 11520024
TI  - Comparison of males' and females' ratios of anterior-cruciate-ligament width to
      femoral-intercondylar-notch width: a cadaveric study.
AB  - The relative incidence of anterior cruciate ligament (ACL) injuries has been
      reported to be significantly higher in females than in males. Although many
      hypotheses have been proposed for this discrepancy, no conclusive explanation has
      reached consensus opinion. The purpose of this study was to evaluate and compare
      fresh-frozen cadaveric knee specimens to determine whether there is a significant
      difference between males' and females' ratios of ACL width to femoral
      intercondylar notch (FIN) width. We evaluated 15 male knees and 11 female knees.
      Data regarding sex, age, side (right or left), and ACL and FIN widths were
      obtained for all specimens. Age of male specimens ranged from 48 to 84 years
      (mean, 63.9 y); age of female specimens ranged from 33 to 96 years (mean, 69.9
      y). Mean ACL width, mean FIN width, and their ratios were calculated. In the male
      specimens, mean ACL width was 10.59 mm (SD, 1.30 mm), mean FIN width was 20.18 mm
      (SD, 2.20 mm), and mean ACL:FIN width ratio was .526 +/- 0.047 (52.6% +/- 4.7% of
      FIN width); in the female specimens, mean ACL width was 8.09 mm (SD, 1.12 mm),
      mean FIN width was 20.50 mm (SD, 1.69 mm), and mean ACL: FIN width ratio was .393
      +/- 0.03 (39.3% +/- 3% of FIN width). Results showed statistically significant
      differences between males' and females' ACL widths (P < .001) and between their
      ACL: FIN width ratios (P< .001) but not between their FIN widths. The significant
      difference between males' and females' ACL widths may be related to the general
      size differences between the groups. It has been speculated that female athletes'
      smaller ACLs may predispose them to ACL ruptures. Perhaps more significant is the
      difference between males' and females' ACL: FIN width ratios, which are
      significantly smaller in females compared with males. This may be directly
      related to the cause of more ACL ruptures in females. Further studies, including
      a good mechanical model, will help elucidate whether this anatomic discrepancy
      correlates clinically.

PMID- 11520025
TI  - Tophaceous gout.

PMID- 11520026
TI  - Triglyceride content in skeletal muscle: variability and the source.
AB  - Intramyocellular triglycerides (imcTG) of skeletal muscle are an important energy
      source for muscle work in mammals. However, the metabolism and regulation of this
      small intracellular neutral lipid pool are largely unknown. This is in part due
      to the difficulties involved with its sampling and measurement introduced by
      contaminants of extramyocellular triglycerides (emcTG). The contents of imcTG
      reported to date for both human and rodent muscle are of unusually high
      variability not only across species, but also within same individuals and even
      same muscle groups. Recent studies suggested that the inherent muscle histologic
      heterogeneity does not appear to be a major source for the high variability as
      previously believed. Rather, the new experimental data showed that the procedures
      commonly used to process muscle specimens before lipid extraction appear
      inadequate to ensure a complete removal of emcTG contaminants. The
      extramyocellular lipid contaminants cause an overestimation of imcTG content and
      markedly increase its variability. Careful and meticulous microdissection has
      been found necessary in order to avoid contamination by emcTG, thereby obtaining
      pure muscle fibers for extraction of imcTG.

PMID- 11520027
TI  - Generation and refinement of peptide mimetic ligands for paratope-specific
      purification of monoclonal antibodies.
AB  - Paratope-specific purification of antibodies has distinct advantages over
      conventional methods of antibody purification with respect to its capacity to
      isolate product of high purity and immunoreactivity. The present report addresses
      the problems of identifying peptide ligands for the purification of antibodies
      reactive with nonprotein antigens. Using an anti-steroid antibody as the model, a
      lead sequence that bound antibody was identified from a peptide phage display
      library. The minimum binding unit in this sequence was deduced using a series of
      truncated peptides synthesized on the heads of polyethylene pins. Replacement Net
      analysis of the minimum binding unit identified peptides with increased affinity
      for the antibody. The affinity-matured peptide mimotope bound antibody in
      solution. By molecular modeling the peptide was superimposable onto estrone-3
      glucuronide localized in the crystal structure of the antibody binding pocket. In
      order to resolve problems of presentation posed by the reversal of orientation of
      the peptide on the affinity matrix compared with the pins, the mimotope peptide
      was synthesized in reverse sequence using d-amino acids. The resulting affinity
      matrix was effective for the purification of antibody. Eluted product
      demonstrated molecular homogeneity and high immunoreactivity. It is concluded
      that the combination of biological and chemical library techniques described
      provides a method for the generation and affinity maturation of mimotopes for
      antibodies against nonprotein antigens.

PMID- 11520028
TI  - A quantitative histochemistry technique for measuring regional distribution of
      acetylcholinesterase in the brain using digital scanning densitometry.
AB  - Studies of brain acetylcholinesterase (AChE) are traditionally based on
      biochemical assays, immunoreactivity, and histochemistry. Conventional
      histochemistry yields rich morphological data from tissue sections but yields
      quantitative results only with great difficulty. Several histochemical methods
      developed in recent years, including microdensitometry, microphotometry, and
      video-based histochemistry, are effective in quantitative and detailed study of
      AChE in tissue sections. However, they are usually time-consuming. As we report
      here, we adapted digital scanning densitometry to quantitate AChE histochemical
      staining in brain sections. The AChE and butyrylcholinesterase (BuChE), as
      measured by the method, were heterogeneously distributed throughout the brain,
      results that are consistent with those obtained by biochemical methods. The
      staining intensity is dependent on section thickness, substrate concentration,
      and reaction time. The cholinesterase inhibitor methyl paraoxon significantly
      decreased AChE staining intensity. Furthermore, data acquired from densitometry
      are similar to those obtained by video-based microscopy or by spectrophotometry.
      The advantage of the densitometric measurements compared to other quantitative
      histochemical methods is that it is very rapid while collecting data that are
      equivalent in quality. Because the digital scanning densitometers provide high
      quality and sensitive imaging, wide dynamic ranges, and convenient image analysis
      software, they are very useful tools in quantitative histochemistry.

PMID- 11520029
TI  - Standardized measurements and differential spectroscopy in microplates.
AB  - Microplates (MPs) are excellent devices for the parallel processing of multiple
      samples for the spectroscopic analysis of chromophores and turbidity, for
      luminometric measurements, for cell culture applications, or simply for sample
      storage, library organization, and other high-throughput (HTP) processes.
      Disadvantages include an ill-defined pathlength, meniscus formation, evaporation,
      and cross-contamination. Here, we have developed a novel MP and lid system which
      can serve to minimize these drawbacks. Cup-like lids are inserted into MP wells.
      Thereby, liquid is pushed aside. The flat bottoms of the cup-like lids guarantee
      a planar interface and a defined pathlength. In addition, the devised MP system
      allows for differential spectroscopic analysis of multiple samples comparable to
      measurements in tandem cuvettes. This was shown by the investigation of the
      binding of reduced nicotinamide adenine dinucleotide to dihydrolipoamide
      dehydrogenase. The MP lid system described offers a low-cost solution for
      standardized spectrophotometric quantitations in any solvent compatible with the
      MP/lid material. In addition to the system's suitability for routine MP
      application, it should be advantageous as a simple and noninvasive method, i.e.,
      no labeling and immobilization of analytes is required for detection of the
      interaction of molecules, for various HTP applications and drug screening
      purposes.

PMID- 11520030
TI  - High-performance liquid chromatography determination of bis(monoacylglycerol)
      phosphate and other lysophospholipids.
AB  - Bis(monoacylglycerol) phosphate (BMP) is a very minor component of the
      phospholipid (PL) fraction in rat uterine stromal cell cultures (U(III) cells).
      Under several culture conditions, including the addition of (n-3) or (n-6)
      polyunsaturated fatty acids, BMP selectively accumulates docosahexaenoic acid
      (DHA). We have recently described the structure of this PL, but its biological
      function is still largely unknown, except for a role in late endosomes
      trafficking. In order to further investigate this function, we have developed a
      sensitive assay for accurate determination of BMP in small biological samples.
      Total PL from cells, labeled or not with trace amount of [3H]DHA, were extracted
      and PL classes separated by thin-layer chromatography. After extraction of the
      gel corresponding to the BMP area, a known amount of an internal standard was
      added. The free hydroxyl groups of PL were totally derivatized with naproxen.
      Derivatized PL were separated by normal-phase high-pressure liquid chromatography
      and quantified using UV absorption at 231 nm. Since the sensitivity of the
      proposed method was about 0.1 nmol for BMP, samples of only 3 x 10(5) cells were
      required. The BMP level was found to be 616 +/- 46 pmol for 10(6) control cells.
      It was increased threefold in starved cells and significantly increased in cells
      cultured in the presence of exogenous phosphatidylglycerol.

PMID- 11520031
TI  - Selective labeling of pulmonary surfactant protein SP-C in organic solution.
AB  - Pulmonary surfactant protein SP-C has been isolated from porcine lungs and
      treated with dansyl isothiocyanate in chloroform:methanol 2:1 (v/v)
      solutions,under conditions optimized to introduce a single dansyl group
      covalently attached to the N-terminalamine group of the protein without loss of
      its native thioesther-linked palmitic chains. The resulting derivative Dans-SP-C
      conserves the secondary structure of native SP-C as well as the ability to
      promote interfacial adsorption of DPPC suspensions and to affect the thermotropic
      behavior of DPPC bilayers. This derivative can be used to characterize lipid
      protein and protein-protein interactions of a native-like SP-C in lipid/protein
      complexes.

PMID- 11520032
TI  - Calorimetric analysis of cephalosporins using an immobilized TEM-1 beta-lactamase
      on Ni2+ chelating sepharose fast flow.
AB  - Two beta-lactamases, penicillinase type I from Bacillus cereus and TEM-1 beta
      lactamase from Haemophilus ducreyi, were immobilized on a Chelating Sepharose
      Fast Flow column loaded with Ni2+ in an active form. Flow-injection analysis of
      beta-lactams was performed by using an enzyme column reactor fitted into the
      enzyme thermistor. With both enzymes it was possible to monitor both penicillins
      and cephalosporins. Moreover, Michaelis constants of the TEM-1 beta-lactamase
      were markedly increased upon immobilization for all substrates, especially
      carbenicillin, cephaloridine, and cefoperazone.

PMID- 11520033
TI  - The enantioselective immunoaffinity extraction of an optically active ibuprofen
      modified peptide fragment.
AB  - Acyl glucuronides are known to produce the covalently bound protein adducts which
      may be the cause of hypersensitivity and toxic responses to acidic drugs. The
      structural analysis of the drug-protein adducts is therefore needed. From this
      point of view, we developed an enantioselective immunoaffinity extraction method,
      which employs an immobilized antibody to specifically isolate peptide fragments
      that have been modified with optically active ibuprofen. Rabbits were immunized
      with (S)-ibuprofen coupled to bovine serum albumin through a beta-alanine group.
      The elicited antibody strongly recognizes the asymmetric center and the
      isobutylphenyl moiety of (S)-ibuprofen and its conjugates but has a low affinity
      for their anti podes. A 0.5-mL aliquot of the immunosorbent (11.5 mg of IgG/mL
      gel) prepared by immobilization of the antibody was capable of retaining up to 1
      microg of (S)-ibuprofen. When a mixture of substance P with (R)- and (S)
      ibuprofen-modified substance P was loaded on the immunosorbent, the (S)-ibuprofen
      modified substance P was selectively retained. The modified peptide was
      quantitatively recovered by elution with 10 mM ammonium acetate buffer (pH
      5.0)/methanol (5:95, v/v). The proposed method would be useful for the structural
      characterization of optically active ibuprofen-modified human serum albumin.

PMID- 11520034
TI  - Quantification of bacterial polysaccharides by the purpald assay: measurement of
      periodate-generated formaldehyde from glycol in the repeating unit.
AB  - We have adapted the purpald assay for measurement of bacterial polysaccharides
      (PS) containing substituted and/or unsubstituted glycol (SG or UG) in residues
      such as glycerol, ribitol, arabinitol, furanosyl galactose, and sialic acid. For
      the purpald assay of UG-containing PS, 50 microL of PS samples was consecutively
      reacted with 50 microL of 16 mM NaIO4 for 20 min, 50 microL of 136 mM purpald
      reagent in 2 N NaOH for 20 min, and 50 microL of 64 mM NaIO4 for 20 min in a 96
      well tissue culture plate followed by a measurement of absorbance at 550 nm with
      a plate reader. For SG-containing PS, conversion of SG to UG with 25 micro;L of
      0.3 N NaOH, 1 h at room temperature for de-O-acetylation followed by 25 microL of
      0.6 M H2SO4, 1 h at 80 degrees C for acid hydrolysis of PS precedes the periodate
      treatment in the purpald assay. The concentration of the samples can be
      calculated from the sample absorbance and the reference standard curve
      constructed from the reference concentrations of the same PS (well-characterized)
      and their corresponding absorbance values assayed in the same plate. The purpald
      assay provides a tool in addition to the existing ones for the measurement of
      glycol-containing PS. Among the usefulness of this method are the determinations
      of the glycerol content in the phospho-glycerol-containing PS and the SG and UG
      contents and structural integrity in PS and conjugate vaccines.

PMID- 11520035
TI  - On the problem of establishing the subcellular localization of Dictyostelium
      retrotransposon TRE5-A proteins by biochemical analysis of nuclear extracts.
AB  - At first sight a protein that is enriched in extracts prepared from nuclei by
      means of biochemical methods can be considered to be a nuclear protein in vivo.
      Although this assumption will hold true for most of the analyzed proteins, it
      could also lead to false interpretations. We analyzed the subcellular
      distribution of endogenous and plasmid-borne proteins derived from the
      retrotransposon TRE5-A of Dictyostelium discoideum. In biochemical fractionation
      experiments the proteins encoded by TRE5-A open reading frame 1 (ORF1p) and the
      putative endonuclease encoded in ORF2 (ENp) were found in the detergent-insoluble
      material containing the nuclei. However, salt extraction of isolated nuclei did
      not considerably release the TRE5-A proteins. Instead, the TRE5-A proteins were
      strongly enriched in a fraction that contained the chromosomal DNA after removal
      of most cytoskeletal and histone proteins. These observations implied that ORF1p
      and ENp were both attached to chromatin in vivo, but this conclusion was
      disproved by the expression of genetic fusions of green fluorescent protein with
      either ORF1p or ENp. We show conclusive evidence that both fusion proteins were
      located as large aggregates of native protein in the cytoplasm of D. discoideum
      cells.

PMID- 11520036
TI  - Extension of the in-gel release method for structural analysis of neutral and
      sialylated N-linked glycans to the analysis of sulfated glycans: application to
      the glycans from bovine thyroid-stimulating hormone.
AB  - This paper reports an extension of the in-gel technique for releasing N-linked
      glycans from glycoproteins for analysis by matrix-assisted laser
      desorption/ionization (MALDI) mass spectrometry reported by B. Kuster, S. F.
      Wheeler, A. P. Hunter, R. A. Dwek, and D. J. Harvey (1997, Anal. Biochem. 250, 82
      101) to allow it to be used for sulfated glycans. The method was used to identify
      N-linked glycans from bovine thyroid-stimulating hormone. Following glycan
      release, either in gel or in solution, the glycans were fractionated directly
      with a porous graphatized carbon column. The sulfated glycans were examined by
      MALDI mass spectrometry in negative ion mode with d-arabinosazone as the matrix
      and both neutral and acidic glycans were examined in positive ion mode from 2,5
      dihydroxybenzoic acid. Negative ion post-source decay spectra were also obtained.
      Twenty-two neutral and fifteen sulfated N-linked glycans were identified and it
      was shown that negligible loss of sulfate groups occurred even though these
      groups are often readily lost during MALDI analysis. The glycans were mainly
      sulfated hybrid and biantennary complex structures. Negative ion post-source
      decay and positive ion collision-induced fragmentation spectra were obtained.

PMID- 11520037
TI  - A fluorometric assay for the determination of 1-deoxy-D-xylulose 5-phosphate
      synthase activity.
AB  - We report a novel fluorometric end-point assay for the determination of 1-deoxy-d
      xylulose 5-phosphate synthase (DXS) activity based on the reaction of 1-deoxy-D
      xylulose 5-phosphate (DX5P) with 3,5-diaminobenzoic acid in an acidic medium to
      form a highly fluorescent quinaldine derivative. The assay was validated in three
      ways: (a) for a fixed amount of DXS in the reaction mixture the emitted
      fluorescence increased linearly with the reaction time, (b) for a fixed reaction
      time fluorescence intensity increased with the concentration of DXS in the
      reaction mixture, and (c) the increase in fluorescence intensity correlated (r =
      0.99; P < 0.002) with the amount of DX5P formed in the reaction mixture
      determined radiometrically. The sensitivity of the fluorometric assay is similar
      to that of the previously described radiometric methods. This assay can be useful
      for the functional characterization of DXS as well as for the screening of DXS
      inhibitors with potential antibiotic, herbicidal, or antimalarial action.

PMID- 11520038
TI  - Direct measurement of ferrous ion transport across membranes using a sensitive
      fluorometric assay.
AB  - The fluorophore, Phen Green SK (PGSK), was assessed for its suitability to be
      used in an assay for ferrous ion transport into membrane vesicles. The long
      wavelengths of excitation and emission (506 and 520 nm, respectively) enable PGSK
      fluorescence to be detected in membranes, such as the chloroplast inner envelope,
      that contain high levels of carotenoids which absorb light at lower wavelengths.
      At low concentrations of Fe2+, less than 3 microM, the interaction between PGSK
      and Fe2+ appears to result in both static and dynamic quenching of the PGSK
      fluorescence. The characteristics of this quenching were used to develop a
      calibration curve to determine the concentration of free Fe2+ at these low
      concentrations. Pronounced quenching of PGSK fluorescence entrapped within
      chloroplast inner envelope membrane vesicles was observed when Fe2+ was added.
      The extent of quenching of PGSK fluorescence trapped inside asolectin vesicles on
      Fe2+ addition was much less. The kinetics of the quenching of PGSK fluorescence
      by Fe2+ in vesicles was quite different from that for PGSK and Fe2+ in solution.
      Using the calibration curve developed for interaction of PGSK and low Fe2+
      concentrations the initial rates of iron transport could be determined for the
      chloroplast inner envelope membranes.

PMID- 11520039
TI  - Quantification of Escherichia coli genomic DNA contamination in recombinant
      protein preparations by polymerase chain reaction and affinity-based collection.
AB  - This study describes the development of a novel assay for the quantification of
      Escherichia coli genomic DNA contamination in recombinant protein samples. The
      technique is based on PCR amplification and digoxygenin labeling of the genes
      encoding 5S ribosomal RNA followed by affinity-based collection and detection.
      Samples containing 1 pg x mL(-1) of extracted E. coli genomic DNA (gDNA) could be
      measured using this method. Using extracted E. coli gDNA as standards, a 35-cycle
      PCR reaction exhibited a linear response versus template concentration between 1
      pg x mL(-1) and1 ng x mL(-1) genomic DNA even when diluted in a variety of
      buffering conditions. Comparison of the novel assay with a traditional filter
      binding and hybridization technique using recombinant protein samples confirmed
      that the procedure was accurate and sensitive. The assay described in this report
      is a safer and less expensive alternative to radioactive techniques employed for
      DNA quantification, utilizing readily available reagents and apparatus.

PMID- 11520040
TI  - Online single-step analysis of blood proteins: the transferrin story.
AB  - The serum iron transport protein human transferrin (hTf) is a glycoprotein (MW
      approximately 79.6 kDa) containing two Asn-linked sites of glycosylation. The
      presence of specific glycoforms of hTf has been used as an indicator of
      carbohydrate-deficient glycoprotein syndrome (CDGS) or an indicator of alcohol
      abuse. The exact nature of the glycoforms described in the literature is
      controversial. In this work we demonstrate that the altered hTf glycoforms have
      lost one or both complete glycan side chains. Furthermore, we demonstrate using a
      combination of online immunoaffinity-postconcentration-mass spectrometry in
      conjunction with a blood spot cartridge that we can determine the relative
      quantities of the hTf glycoforms using <5 microL blood in under 30 min. This is
      in contrast to previous methods that used 1 mL and took 4 days. We show that this
      method can be useful to analyze hTf from CDGS and alcoholic patients.

PMID- 11520041
TI  - High-throughput assays for botulinum neurotoxin proteolytic activity: serotypes
      A, B, D, and F.
AB  - Botulinum neurotoxins (BoNT) are zinc metalloproteases that cleave and inactivate
      cellular proteins essential for neurotransmitter release. Because the paralytic
      effect of BoNT is a consequence of its enzymatic activity, selective inhibitors
      may be useful as drugs or as tools for further research. To expedite inhibitor
      discovery, we developed high-throughput, solid-phase protease activity assays for
      four of the seven BoNT serotypes: A, B, D, and F. Each assay consisted of a
      cleavable oligopeptide, based on the natural substrate sequence, labeled with
      fluorescein and covalently attached to maleimide-activated multiwell plates.
      Solutions of holotoxin or nontoxic catalytic domain of BoNT were incubated in
      substrate-coated wells, with or without test compounds, followed by transfer and
      assay of solubilized product in a multiwell fluorometer. Routine toxin
      concentrations ranged from 10 to 100 ng/ml, but concentrations as low as 2 ng/ml
      gave reproducible signals. The fluorescence assays were selective, gave very low
      background readings, and were stable upon prolonged storage. Using the nontoxic
      catalytic domain of BoNT A, we determined the relative inhibitory potencies of a
      family of structurally related pseudotripeptide compounds. Unlike previous
      methods, our assays did not employ antibodies or reverse-phase extraction steps,
      only well-to-well transfers, and were easily adapted to a high-throughput
      automated environment.

PMID- 11520042
TI  - Plasmid purification using membrane-based anion-exchange chromatography.

PMID- 11520043
TI  - Solid-phase extraction of lipid from Saccharomyces cerevisiae followed by high
      performance liquid chromatography analysis of coenzyme Q content.

PMID- 11520044
TI  - High transfection efficiency of human umbilical vein endothelial cells using an
      optimized calcium phosphate method.

PMID- 11520045
TI  - A simple, handheld apparatus for generating small volumes of 15N2 from 15N
      labeled ammonium salts.

PMID- 11520046
TI  - High-throughput polymerase chain reaction cleanup in microtiter format.

PMID- 11520047
TI  - Possible applications of conditionally immortalized tissue cell lines with
      differentiation functions.
AB  - If all individual cell types of the body could be clonally isolated and stocked,
      similar to cDNA or genomic DNA libraries, they would be invaluable for studying
      the tissue and cellular functions. We developed a new method of establishing
      conditionally immortalized cell lines that retain differentiated cell functions
      similar to the original tissues, using temperature-sensitive (ts) simian virus 40
      large tumor antigen gene transgenic animals. In this review the properties of
      such conditionally immortalized cell lines and their possible applications are
      discussed.

PMID- 11520048
TI  - Sphingosine kinase regulates hepatoma cell differentiation: roles of hepatocyte
      nuclear factor and retinoid receptor.
AB  - In hepatoma Huh-7 cells, inhibition of sphingosine kinase (SphK) activity by N,N
      dimethylsphingosine (DMS) resulted in up-regulated production of liver-specific
      serum proteins including albumin and alpha-fetoprotein (AFP). The changes in
      these protein levels coincided well with those of two liver-enriched
      transcription factors, hepatocyte nuclear factor (HNF)-1 and -4, which regulate a
      number of liver-specific genes at the transcriptional level. Moreover, DMS
      induced the expression of retinoic acid receptor-alpha and retinoid X receptor
      alpha. In DMS-treated cells, 9-cis retinoic acid (RA) further enhanced HNF-4alpha
      and albumin expression but it inhibited AFP accumulation. These results suggest
      that activation of SphK disengages cells from their liver-specific phenotype, and
      that 9-cis RA further induces differentiation of hepatoma cells when SphK
      activity is inhibited.

PMID- 11520049
TI  - Analysis of 825C/T polymorphism of G proteinbeta3 subunit in obese/diabetic
      Japanese.
AB  - The GNB3 825C/T polymorphism, which is common worldwide, is associated with
      enhanced G-protein activation. The frequency of 825-T allele was increased with
      body mass index (BMI) and finally had a high frequency in relatively mild obese
      (BMI >27 kg/m(2)) subjects in some populations. In the present study, we
      investigated 208 severely obese [BMI >or=30 kg/m(2) (97th percentile)] Japanese
      subjects including 146 probands with diabetes. No increase in the 825-T allele
      frequency was observed in the 208 severely obese and even in a subgroup of the 55
      most obese [BMI >or=35 kg/m(2) (99.7th percentile)] subjects compared with that
      in 150 controls (BMI <25 kg/m(2)) (0.48 and 0.48 vs 0.51, respectively). Also,
      the frequency was not increased in the 146 obese subjects with diabetes (0.48).
      We concluded that the 825-T allele is not associated with obesity or diabetes
      associated with obesity at least in the Japanese population.

PMID- 11520050
TI  - Both heavy strand replication origins are active in partially duplicated human
      mitochondrial DNAs.
AB  - The replication of human mitochondrial DNA (mtDNA) is initiated from a pair of
      displaced origins, one priming continuous synthesis of daughter-strand DNA from
      the heavy strand (OH) and the other priming continuous synthesis from the light
      strand (OL). In patients with sporadic large-scale rearrangements of
      mitochondrial DNA (i.e., partially-deleted [Delta-mtDNA] and partially-duplicated
      [dup-mtDNA] molecules), the dup-mtDNAs typically contain extra origins of
      replication, but it is unknown at present whether they are competent for
      initiation of replication. Using cybrids harboring each of two types of dup
      mtDNAs-one containing two OHs and two OLs, and one containing two OHs and one OL
      we used ligation-mediated polymerase chain reaction (LMPCR) to measure the
      presence and relative amounts of nascent heavy strands originating from each OH.
      We found that the nascent heavy strands originated almost equally from the two
      OHs in each cell line, indicating that the extra OH present on a partially
      duplicated mtDNA is competent for heavy strand synthesis. This extra OH could
      potentially confer a replicative advantage to dup-mtDNAs, as these molecules may
      have twice as many opportunities to initiate replication compared to wild-type
      (or partially deleted) molecules.

PMID- 11520051
TI  - Identification of immunostimulatory DNA-induced genes by suppression subtractive
      hybridization.
AB  - Bacterial DNA and related synthetic immunostimulatory oligodeoxyribo-nucleotides
      (ISS-ODN) have stimulatory effects on mammalian immune cells through a Toll-like
      receptor, TLR9. Genes upregulated in ISS-ODN-stimulated immune cells are
      obviously significant to delineate the mechanism of the induced innate immunity.
      Employing suppression subtractive hybridization (SSH), we have generated a
      profile of genes induced by ISS-ODN in spleen cells. Sequencing of 87 clones
      isolated by the SSH showed 39 clones corresponding to known mouse genes in the
      public database. Eleven clones appeared to possess 80-90% homology with known
      mouse genes and the remaining 37 clones showed no significant homology with any
      known mouse genes. A series of known genes which have not previously been
      reported to be induced with ISS-ODN were confirmed to be induced in ISS-ODN
      stimulated bone marrow-derived macrophages: NF-kappaB p105, IRF-1, PA28beta,
      IRG2, and MyD88. These genes were suggested to be involved in the molecular
      process of innate host defense mechanisms.

PMID- 11520052
TI  - Unique regulation of c-Jun N-terminal kinase by PYK2/CAK-beta in angiotensin II
      stimulated vascular smooth muscle cells.
AB  - Activation of tyrosine kinases is believed to play a central role in angiotensin
      II (AngII) signaling. Here, we have investigated whether a tyrosine kinase, PYK2,
      is functionally involved in AngII-induced c-Jun N-terminal kinase (JNK)
      activation in vascular smooth muscle cells (VSMCs). Adenovirus expressing PYK2
      kinase-inactive mutant K457A or a tyrosine phosphorylation site mutant Y402F was
      transfected in VSMCs. AngII-induced JNK phosphorylation was markedly enhanced by
      K457A, whereas it was suppressed by Y402F. Protein synthesis induced by AngII was
      also enhanced by K457A and inhibited by Y402F. In this regard, K457A suppressed
      PYK2 kinase activation by AngII, whereas it enhanced AngII-induced PYK2 Tyr(402)
      phosphorylation. By contrast, Y402F inhibited PYK2 Tyr(402) phosphorylation,
      whereas it markedly enhanced AngII-induced PYK2 kinase activation. Thus, we
      conclude that PYK2 kinase activity negatively regulates JNK activation and
      protein synthesis, whereas Tyr(402) phosphorylation positively regulates these
      events in AngII-stimulated VSMCs, suggesting a unique role of PYK2 in mediating
      vascular remodeling.

PMID- 11520053
TI  - LL-Z1271alpha: an interleukin-1beta production inhibitor.
AB  - LL-Z1271alpha, a fungal metabolite, dose-dependently inhibited interleukin-1beta
      (IL-1beta) production in lipopolysaccharide (LPS)-stimulated human whole blood.
      Oral administration of LL-Z1271alpha to LPS-challenged mice caused significant
      lowering in the IL-1beta levels in peritoneal cavity. Data presented suggest that
      LL-Z1271alpha inhibits IL-1beta production by a novel mechanism as the inhibitory
      activity was not due to effects on caspase-1 (IL-1beta converting enzyme), the
      ATP-induced release mechanism or a lysosomotrophic effect.

PMID- 11520054
TI  - Kinetic stability of designed glycosylation mutants of Coprinus cinereus
      peroxidase.
AB  - The effect of glycans and surface mutations on protein unfolding induced by heat
      or urea has been studied. Removal of the only native high mannose type glycan in
      the N142P, N142T, and N142D CIP mutants reduced the lifetime to half of that of
      wtCIP at irreversible conditions of unfolding. The effect was moderate at
      reversible conditions. Five glycomutants designed to have 0, 1, 2, 4 and 6N
      glycans showed a correlation between increased carbohydrate mass and increased
      stability toward irreversible unfolding. The results are in agreement with a
      dampening effect of glycans on backbone fluctuation in both the native and the
      unfolded states. However, experiments in reversible conditions were less clear
      because of additional effects of an increasing number of amino acid substitutions
      and aggregation. Examples of strong effects from minor surface changes were also
      observed.

PMID- 11520055
TI  - Effect of N-glycosylation on ligand binding affinity of rat V1a vasopressin
      receptor.
AB  - A rat Vla vasopressin (rVla) receptor has two putative N-glycosylation sites at
      14th and 27th amino acid asparagine in the extracellular N-terminus. In the
      present study, we examined the possible roles of N-glycosylation of the N
      terminus in the receptor function. Three point mutants for deglycosylated rVla
      receptor were generated in which the 14th and/or the 27th asparagine was replaced
      with glutamine, namely N14Q, N27Q, and N14:27Q, each tagged with an enhanced
      green fluorescent protein (EGFP) at their C-termini, and transfected to COS-7 or
      HEK292 cells. The two single mutants and a double mutant have progressively
      smaller molecular mass compared to the wild-type receptor as determined by
      immunoblot analysis, indicating that the two sites are effectively glycosylated
      in vivo. The maximal ligand binding capacities of three mutant receptors were
      comparable to that of wild-type (17.02 +/- 1.32 pmol/g protein) with modest
      changes in ligand binding affinities: N27Q and N14:27Q had decreased binding
      affinities compared to N14Q and wild-type receptors. The reduced binding
      affinities of the deglycosylated mutants are not likely due to the impaired
      intracellular transport since their traffickings were indistinguishable from one
      another. Taken together, these results suggest that the N-glycosylation at the
      two sites of the N-terminus of rV1a receptor minimally affects the surface
      expression and trafficking of the receptor.

PMID- 11520056
TI  - A comprehensive analysis of gene expression profiles in a yeast N-glycosylation
      mutant.
AB  - Although protein N-glycosylation is critical to many cell functions, its
      downstream targets remain largely unknown. In all eukaryotes, N-glycosylation
      utilizes the lipid-linked oligosaccharide (LLO) precursor, whose synthesis is
      initiated by the ALG7 gene. To elucidate the key signaling and metabolic events
      affected by N-glycosylation, we performed genomewide expression profiling of
      yeast cells carrying a hypomorphic allele of ALG7. DNA microarrays showed that of
      more than 97% of known or predicted yeast genes, 29 displayed increased
      expression while 23 were repressed in alg7 mutants. Changes in transcript
      abundance were observed for a and alpha mating-type genes, for genes functioning
      in several mitogen-activated protein kinase (MAPK) cascades, as well as in
      phosphate, amino acid, carbohydrate, mitochondrial and ATP metabolism. Therefore,
      DNA microarrays have revealed direct and indirect targets, including internal
      feedback loops, through which N-glycosylation affects signaling and metabolic
      activities and is functionally linked with cellular regulatory circuitry.

PMID- 11520057
TI  - Involvement of ERK and protein tyrosine phosphatase signaling pathways in EGCG
      induced cyclooxygenase-2 expression in Raw 264.7 cells.
AB  - Prostaglandins play regulatory roles in a variety of physiological and
      pathological processes in immune response and inflammation. Epigallocatechin-3
      gallate (EGCG) is known to potent antitumor agent with antioxidant property. We
      first investigated the effect of EGCG on the production of prostaglandin E(2)
      (PGE(2)) and the expression of cyclooxygenase-2 (COX-2), the rate-limiting enzyme
      in the synthesis of PGE(2), using macrophage cell line, Raw264.7. Our results
      showed that COX-2 expression and PGE(2) production are upregulated by EGCG
      treatment and that this induction of COX-2 is regulated in part at the
      transcriptional level. In addition, we demonstrated the signal transduction
      pathway of mitogen-activated protein kinase (MAP kinase) in EGCG-mediated COX-2
      expression. The MEK inhibitor (PD098059) prevented EGCG-induced COX-2 expression,
      whereas sodium orthovanadate (protein-tyrosine phosphatase inhibitor)
      significantly enhanced COX-2 expression and PGE(2) production. These results
      suggest that EGCG mediated COX-2 expression and PGE(2) production is associated
      with the activation of both the ERK and protein-tyrosine phosphatase signaling
      pathways.

PMID- 11520058
TI  - Arsenic trioxide induces G2/M growth arrest and apoptosis after caspase-3
      activation and bcl-2 phosphorylation in promonocytic U937 cells.
AB  - Arsenic trioxide has recently been shown to inhibit growth and induce apoptosis
      in acute promyelocytic leukemia (APL), but little is known about the molecular
      mechanisms mediating these effects. Here we demonstrate that treatment of
      promonocytic U937 cells with arsenic trioxide leads to G2/M arrest which was
      associated with a dramatic increase in the levels of cyclin B and cyclin B
      dependent kinase and apoptosis. We further show that apoptosis occurs after bcl-2
      phosphorylation and caspase-3 activation followed by cleavage of PARP and PLC
      gamma1 degradation and DNA fragmentation. The arsenic trioxide-induced apoptosis
      could be blocked by the protein synthesis inhibitor cycloheximide. In addition,
      pretreatment of U937 cells with the DNA polymerase inhibitor aphidicolin also
      blocked apoptosis, but did not cause the arrest of cells in the G2/M phase. The
      findings suggest that arsenic trioxide exerts its growth-inhibitory effects by
      modulating expression and/or activity of several key G2/M regulatory proteins.
      Furthermore, arsenic trioxide-mediated G2/M arrest correlates with the onset of
      apoptosis.

PMID- 11520059
TI  - Differential regulation of adipocytokine mRNAs by rosiglitazone in db/db mice.
AB  - The precise mechanism by which PPARgamma activation by thiazolidinediones (TZDs)
      improves insulin sensitivity is still unclear. Recent studies have focused on the
      role of adipocytokines in metabolic control and their regulation by TZDs. In this
      study, we compared the chronic effects of antihyperglycemic doses of the TZD
      rosiglitazone, the beta3-adrenoceptor agonist BRL-35135, and the PPARalpha
      agonist Wy-14,643 on the mRNA expression of adipocytokines in WAT of db/db mice.
      Rosiglitazone treatment decreased adiponectin and resistin mRNA levels by 57 and
      72%, respectively (P < 0.001), with no effect on the level of TNFalpha or
      RELMalpha transcripts. In comparison, Wy-14,643 reduced adiponectin transcript
      levels by 31% (P = 0.015) while BRL-35135 increased RELMalpha mRNA expression by
      245% (P < 0.001) without effect on the other transcripts. Our results indicate
      that although a reduction in adiponectin and resistin mRNA levels in WAT by
      rosiglitazone treatment of diabetic mice may contribute to the antidiabetic
      effects, an alteration in TNFalpha, adiponectin, resistin, or RELMalpha mRNA
      expression is not absolutely required for the regulation of blood glucose
      concentration in the db/db mouse.

PMID- 11520060
TI  - Syndecan-2 expression in colorectal cancer-derived HT-29 M6 epithelial cells
      induces a migratory phenotype.
AB  - Members of the heparan sulfate proteoglycan family, the syndecans have emerged as
      integrators of extracellular signals, such as ECM components or growth factors,
      that activate cytoplasmic signaling cascades and regulate cytoskeletal functions.
      Specifically, syndecan-2 has been implicated in various cellular processes, from
      differentiation to migration, including its participation in cell-cell and cell
      matrix adhesion. Here, we focused on the involvement of syndecan-2 in epithelial
      versus mesenchymal differentiation. Colorectal cancer-derived HT-29 M6 epithelial
      cells were stably transfected with full-length syndecan-2 cDNA, and the effect on
      cell morphology, adhesion, and mobility was evaluated. Characteristic features of
      migratory cells such as loss of intercellular contacts, flatter shape and
      multiple membrane projections were observed in syndecan-2 transfectants. Western
      blot analysis of the major component of epithelial adherens junctions, E
      cadherin, revealed decreased expression levels. Furthermore, syndecan-2 induced
      stronger adhesion to collagen type I, specifically inhibited by heparin. This was
      correlated with an increased ability for migration, as demonstrated by wound
      healing experiments and transwell assays, without affecting their growth rate.
      These results indicate that syndecan-2 expression in mucus-secreting HT-29 M6
      cells induces differentiation toward a migratory mesenchymal-like phenotype.

PMID- 11520061
TI  - Isolation of normal epithelial cells adapted to grow at nonphysiological
      concentration of magnesium.
AB  - Extracellular magnesium (Mg) depletion inhibits the growth of the HC11 normal
      mammary epithelial cells. In this study we found that an acute increase in
      extracellular Mg generally exerts a positive effect on the growth of these cells.
      We also isolated and characterized two derivatives adapted to grow and
      proliferate at nonphysiological concentration of Mg. The growth properties of the
      HC-LMg cells at 25 microM Mg were comparable to those of the parental HC11 cells
      in the regular medium (0.5 mM Mg) despite an increased expression of the CDK
      inhibitor p27(Kip1). They also showed a reduced dependence from serum to grow.
      The HC-HMg cells have been adapted to grow and proliferate at an increased (45
      mM) Mg concentration. Cell total Mg content was 19.6, 9.7, and 20.1 nmol/mg
      protein in the HC11, HC-LMg, and HC-HMg cells, respectively. Thus, we have
      isolated derivatives of normal epithelial cells which are able to maintain Mg
      content in a physiological range in the face of different extracellular
      concentration gradients and will be a valuable tool for further studies on the
      regulation of Mg homeostasis in eukaryotic cells.

PMID- 11520062
TI  - Formation of inverted hexagonal phase in SDPE as observed by solid-state (31)P
      NMR.
AB  - Docosahexaenoic acid (DHA), the longest and most unsaturated fatty acid commonly
      found in biological membranes, is known to affect various membrane properties. In
      a variety of cell membranes, DHA is primarily incorporated in
      phosphatidylethanolamines, where its function remains poorly understood. In order
      to understand the role of DHA in influencing membrane structure, we utilize (31)P
      NMR spectroscopy to study the phase behavior of 1-stearoyl-2-docosahexaenoyl-sn
      glycerophosphoethanolamine (SDPE) in comparison to 1-palmitoyl-2-oleoyl-sn
      glycerophosphoethanolamine (POPE) from 20 to 50 degrees C. Spectra of SDPE
      phospholipids show the formation of inverted hexagonal phase (H(II)) from 20 to
      50 degrees C; in contrast, POPE mutilamellar dispersions exist in a lamellar
      liquid-crystalline phase (L(alpha)) at the same temperatures. The ability of SDPE
      to adopt nonbilayer phases at a physiological temperature may indicate its role
      in imparting negative curvature stress upon the membrane and may affect local
      molecular organization including the formation of lipid microdomains within
      biological membranes.

PMID- 11520063
TI  - Peroxynitrite-induced tyrosine nitration and inhibition of protein kinase C.
AB  - Protein kinase C (PKC) is an important intracellular signaling molecule whose
      activity is essential for a number of aspects of neuronal function including
      synaptic plasticity. We investigated the regulation of PKC activity by reactive
      nitrogen species in order to examine whether such species regulate PKC in
      neurons. Neither autonomous nor cofactor-dependent PKC activity was altered when
      either hippocampal homogenates or rat brain purified PKC were incubated briefly
      with three different nitric oxide donor compounds. However, brief incubation of
      either hippocampal homogenates or purified PKC with peroxynitrite (ONOO(-))
      inhibited cofactor-dependent PKC activity in a manner that correlated with the
      nitration of tyrosine residues on PKC, suggesting that this modification was
      responsible for the inhibition of PKC. Consistent with this idea, reducing agents
      had no effect on the inhibition of PKC activity caused by ONOO(-). Because there
      are numerous PKC isoforms that differ in the composition of the regulatory
      domain, we studied the effect of ONOO(-) on various PKC isoforms. ONOO(-)
      inhibited the cofactor-dependent activity of the alpha, betaII, epsilon, and zeta
      isoforms, indicating that inhibition of enzymatic activity by ONOO(-) was not PKC
      isoform-specific. We also were able to isolate nitrated PKCalpha and PKCbetaII
      from ONOO(-)-treated hippocampal homogenates via immunoprecipitation.
      Collectively, our findings support the hypothesis that ONOO(-) inhibits PKC
      activity via tyrosine nitration in neurons.

PMID- 11520064
TI  - Identification of a PDZ domain containing Golgi protein, GOPC, as an interaction
      partner of frizzled.
AB  - The frizzled gene is evolutionally conserved in a wide variety of organisms
      including mammals, and in Drosophila, frizzled is implicated in the development
      of planar polarity. We describe here the isolation and characterization of a
      Golgi protein, GOPC, as a frizzled interacting protein. GOPC comprises one PDZ
      domain, two coiled-coil motifs and two evolutionally conserved regions.
      Immunofluorescence studies indicated that a significant fraction of GOPC protein
      was localized in the Golgi apparatus. Using a series of deletion mutants, we show
      that both coiled-coil motifs and a C-terminal conserved region were required for
      its Golgi localization. Interestingly, deletion mutants that lack a N-terminal
      conserved region or coiled-coil motifs formed aggresome-like perinuclear
      structure. Interaction of GOPC and frizzled was observed both in vivo and in
      vitro, and the PDZ domain of GOPC and the C-terminal Ser/Thr-X-Val motif of
      frizzled were required for their interaction. Immunofluorescence studies
      indicated that, although frizzled was a membrane protein, it was localized at the
      Golgi apparatus as well, and colocalization of GOPC and frizzled at the Golgi
      apparatus was observed. Furthermore, when GOPC was coexpressed with frizzled,
      translocation of GOPC to the plasma membrane was observed. Importantly, brefeldin
      A interrupted not only the localization of GOPC to the Golgi apparatus but also
      the translocation of frizzled to the plasma membrane, indicating that the Golgi
      structure was required for the proper subcellular localization of frizzled. Taken
      together, these results indicate that GOPC may play a role in the vesicle
      transport of frizzled from the Golgi apparatus to the plasma membrane.

PMID- 11520065
TI  - Green fluorescent protein-transgenic rat: a tool for organ transplantation
      research.
AB  - The purpose of this study is to evaluate green fluorescent protein (GFP)
      transgenic rats for use as a tool for organ transplantation research. The GFP
      gene construct was designed to express ubiquitously. By flow cytometry, the cells
      obtained from the bone marrow, spleen, and peripheral blood of the GFP transgenic
      rats consisted of 77, 91, and 75% GFP-positive cells, respectively. To examine
      cell migration of GFP-positive cells after organ transplantation, pancreas graft
      with or without spleen transplantation, heart graft with or without lung
      transplantation, auxiliary liver and small bowel transplantation were also
      performed from GFP transgenic rat to LEW (RT1(1)) rats under a 2-week course of
      0.64 mg/kg tacrolimus administration. GFP-positive donor cells were detected in
      the fully allogenic LEW rats after organ transplantation. These results showed
      that GFP transgenic rat is a useful tool for organ transplantation research such
      as cell migration study after organ transplantation without donor cell staining.

PMID- 11520066
TI  - Tumor-specific cytotoxic T lymphocyte responses against chondrosarcoma with HLA
      haplotype loss restricted by the remaining HLA class I allele.
AB  - Although loss of HLA expression by malignant cells has also been demonstrated, it
      has not been clarified how the loss of HLA expression observed in vitro actually
      results in immune escape. We demonstrated two major findings: (i) a part of
      chromosome 6 coding for HLA haplotypes was deleted from the genome of
      chondrosarcoma cell line, OUMS-27; furthermore, immunohistostaining for HLA-A11
      showed that the original chondrosarcoma tissue lost the expression of HLA-A11,
      implicating that HLA haplotype loss was already present in the original tumor
      tissue and (2) HLA class I-restricted and autologous tumor-specific cytotoxic T
      cells (CTL) were generated from peripheral blood lymphocytes of the patient with
      chondrosarcoma, from whom OUMS-27 originated. This CTL line was maintained by
      weekly stimulation with OUMS-27, and lysed OUMS-27 in an HLA-A24 dependent manner
      but did not either K562 or autologous (EBV)-transformed B cells. These
      observations indicated that OUMS-27 and its original tumor are still immunogenic
      and can present antigen peptides with the remaining HLA-A24, even if HLA
      expression is partially lost. Tumor specific immunotherapy can be applied to the
      treatment of malignancies, even if HLA expression is partially lost.

PMID- 11520067
TI  - Gene expression profiling in human esophageal cancers using cDNA microarray.
AB  - Human esophageal cancer cell lines and human esophageal cancer tissues were
      profiled on cDNA microarrays. In esophageal cancer cell lines, KYAE and OE-33
      (adenocarcinomas) were distinguished from KYSE series (squamous cell carcinomas).
      Although SK-GT-4 and TE7 were derived from adenocarcinomas, they had a
      comparatively similar expression profile to the KYSE series. A set of genes whose
      expression commonly either increased or decreased in cancer cell lines was
      identified. Genes that were characteristically expressed in KYAE and OE-33 were
      also identified. The gene expression profiles of cancer tissues (CTs) were
      remarkably different from those of the cancer cell lines (CCLs). Notable
      differences between CCLs and CTs were observed in matrix metalloproteinases,
      plasminogen activator, collagens, paxillin, and thrombospondin 2, etc., whose
      expression was not increased in CCLs but increased in CTs. Twenty-three genes
      were extracted to categorize patients according to their prognoses, and
      clustering analyses, using these genes, were performed successfully.

PMID- 11520068
TI  - Intravenously injected FK506 failed to inhibit hippocampal calcineurin.
AB  - FK506 (tacrolimus) is known as an inhibitor for calcineurin and is used in
      numerous research fields. It is not clear whether intravenously injected FK506
      inhibits neuronal calcineurin. We measured the calcineurin activities of normal
      and postischemic rat hippocampi after intravenous injection of FK506 (3 mg/kg).
      Intravenously injected FK506 had no inhibitory effect on calcineurin activity in
      the hippocampi of normal and postischemic rats, whereas FK506 inhibited the
      calcineurin in vitro (purified enzyme, hippocampal homogenate, and hippocampal
      slice culture homogenate). Thus, it is considered that intravenously injected
      FK506 does not act on intraneuronal calcineurin and that several effects of FK506
      are not due to the inhibition of neuronal calcineurin.

PMID- 11520069
TI  - BAG-1M, an isoform of Bcl-2-interacting protein BAG-1, enhances gene expression
      driven by CMV promoter.
AB  - BAG-1M, one of the isoforms of BAG-1, was reported to bind to DNA and stimulate
      general transcription when cells were stressed by heat shock (Zeiner, M., et al.,
      Proc. Natl. Acad. Sci. USA 96, 10194-10199, 1999). Here we show that BAG-1M binds
      and enhances transcriptional activity of Cytomegalovirus (CMV) early gene
      promoter under unstressed conditions. This activity is unique to BAG-1M in that
      other isoforms, BAG-1S and BAG-1L, are much weaker in this activity, although all
      of the isoforms share common ubiquitin-like domain and BAG domain interacting
      with Hsp70/Hsc70. Deletion analysis of BAG-1M showed that C-terminal BAG domain
      is necessary to enhance the CMV promoter activity, suggesting that interaction
      with Hsp70/Hsc70 proteins may mediate this function. Another mutation in N
      terminus, BAG-1M K(2-4)A, lost DNA binding capacity and majority of the promoter
      enhancing activity. Our study demonstrates that both N-terminal DNA binding site
      and C-terminal Hsp70/Hsc70 binding site of BAG-1M play an important role in
      enhancing the CMV promoter activity.

PMID- 11520070
TI  - Expression analysis and chromosomal assignment of PRA1 and RILP genes.
AB  - PRA1 (prenylated Rab acceptor) is a general regulator of Rab proteins, while RILP
      (Rab interacting lysosomal protein) is a specific effector for Rab7. It has been
      shown that PRA1 interacts with Rab proteins and with VAMP2. Therefore PRA1 is
      probably an important factor for membrane traffic, linking together the function
      of Rab proteins and SNAREs. RILP has a key role in the control of transport to
      degradative compartments together with Rab7 and probably links Rab7 function to
      the cytoskeleton. Here we have studied by Northern blot the expression of the two
      genes in several different human tissues. The 0.8-kb mRNA for human PRA1 is
      ubiquitously expressed, while the two mRNAs for RILP are differentially
      expressed. In addition, we have assigned the human PRA1 gene to chromosome
      19q13.13-q13.2 and the human RILP gene to chromosome 17p13.3.

PMID- 11520071
TI  - IsCT, a novel cytotoxic linear peptide from scorpion Opisthacanthus
      madagascariensis.
AB  - A novel cytotoxic linear peptide, IsCT, was characterized from scorpion
      Opisthacanthus madagascariensis. It is a linear peptide with a molecular weight
      of 1501.9 Da composed of 13 amino acid residues without cysteines. MS/MS analysis
      showed that its C-terminal is amidated. The identity of IsCT is re-confirmed by
      comparing the chemical synthesized peptide with the natural one. IsCT
      demonstrated antimicrobial activity against both gram-positive and gram-negative
      bacteria and hemolytic activity to sheep red blood cells. Also, it can release
      histamine from rat peritoneal mast cells. The CD absorption suggested that IsCT
      had an alpha-helix configuration in aqueous TFE. IsCT is one of the shortest
      natural cytotoxic peptides described, and it will be a suitable model for
      studying peptide-lipid interactions.

PMID- 11520072
TI  - Stretching short biopolymers using optical tweezers.
AB  - Optical tweezers is a useful technique to study single molecules. It has been
      applied to stretch biopolymers in several approaches. However, these approaches
      may not be appropriate to measure short biopolymers. In the present study, the
      optical signals of beads in different situations were studied. A new method was
      developed for stretching short biopolymers, as short as 300 nm in length. This
      new method was successfully applied to determine the stiffness of procollagen I
      molecules.

PMID- 11520073
TI  - Inhibition of protein tyrosine phosphatases suppresses P-selectin exocytosis in
      activated human platelets.
AB  - P-selectin (CD62P), a cell adhesion molecule for most leukocytes, is stored in
      the alpha-granules of platelets and the Weibel-Palade bodies of endothelial
      cells. Upon thrombogenic and inflammatory challenges, P-selectin is rapidly
      expressed, by exocytosis, on activated platelets and stimulated endothelial
      cells. However, little is known for the molecular mechanisms governing the
      regulation of the rapid mobilization of P-selectin in these cells. Here we show
      that phenylarsine oxide (PAO) and diamide (both were inhibitors for protein
      tyrosine phosphatases), but not genistein (an inhibitor for protein tyrosine
      kinases), adenosine, wortmannin and LY294002 (all were inhibitors for
      phosphatidylinositol 3- and 4-kinases), could inhibit P-selectin exocytosis on
      activated platelets and could abolish the P-selectin mediated aggregation of
      activated platelets to neutrophils. However, PAO did not attenuate the P-selectin
      mediated adhesion of human promyeloid HL-60 cells on the stimulated endothelial
      cells under flow conditions. Further, PAO had no detectable effects on the
      exocytosis of P-selectin in the stimulated endothelial cells. These results
      indicate that protein tyrosine phosphatases are necessary for P-selectin
      exocytosis on the activated platelets, but not on the stimulated endothelial
      cells, and suggest that inhibitors for protein tyrosine phosphatases may be
      potentially valuable for treatment of platelet/leukocyte aggregation.

PMID- 11520074
TI  - Clear suppression of Th1 responses but marginal amelioration of autoimmune
      manifestations by IL-12p40 transgene in MRL-FAS(lprcg)/FAS(lprcg) mice.
AB  - To investigate the effects of overproduction of IL-12p40, a potent antagonist
      against IL-12, on lupus-like autoimmune disease in vivo, we generated p40
      transgenic MRL-Fas(lprcg)/Fas(lprcg) mice. Serum p40 and IL-12 levels were 600-
      to 8000-fold and 3- to 20-fold higher in transgenic (p40-lpr(cg)) than
      nontransgenic (lpr(cg)) mice, respectively. Serum IFN-gamma levels increased
      after 3 months of age in lpr(cg) and this age-related increase was completely
      abrogated in p40-lpr(cg). Serum IL-4 levels were the same in both mice.
      Production of IgM and IgG anti-double-stranded DNA (dsDNA) antibodies was
      significantly lower in p40-lpr(cg). Anti-dsDNA antibodies decreased in Th1
      dependent IgG2a but increased in the Th2-dependent IgG1 subclass significantly in
      p40-lpr(cg). Proteinuria, glomerulonephritis, and survival were only marginally
      ameliorated in p40-lpr(cg). The results suggest that excess p40 production in
      vivo may suppress Th1 responses in autoantibody and IFN-gamma production but lead
      to minimal improvement of clinical manifestations of autoimmune disease in this
      mouse model.

PMID- 11520075
TI  - Human milk anti-inflammatory component contents during acute mastitis.
AB  - Mastitis is a common complication of human lactation. We examined milk specimens
      from eight women with clinical mastitis to determine their content of anti
      inflammatory components. Antioxidant activity (spontaneous cytochrome c reducing
      activity), selected pro-inflammatory cytokines (IL-6, IL-1beta), selected
      endogenous cytokine control molecules (sIL-6R, sIL-1RII, and sTNFRI),
      lactoferrin, Na(+):K(+) ratios, and milk bioactivities that cause shedding of sIL
      1RII from human polymorphonuclear leukocytes (PMN), suppress PMN aggregation, and
      suppress PMN adherence responses were not increased compared to normal milks.
      Neither the bioactivities that deplete PMN intracellular Ca(2+) stores nor those
      that block Ca(2+) influx into fMLP-stimulated PMN were significantly increased in
      mastitis milks. In contrast, levels of TNFalpha, sTNFRII, and IL-1RA and
      bioactivities that cause shedding of sTNFRI from human PMN were significantly
      increased compared to normal milks. Mastitis milk has the same anti-inflammatory
      components and characteristics of normal milk, with elevations in selected
      components/activities that may help protect the nursing infant from developing
      clinical illness due to feeding on mastitis milk.

PMID- 11520076
TI  - Generation of melanoma-specific, cytotoxic CD4(+) T helper 2 cells: requirement
      of both HLA-DR15 and Fas antigens on melanomas for their lysis by Th2 cells.
AB  - Recognition of melanoma antigens by HLA class-II-restricted CD4(+) T lymphocytes
      has been investigated. Two cytotoxic CD4(+) T cell lines were established by
      stimulating PBLs from a melanoma patient with either parental or IFN-gamma
      transduced autologous tumor cells. These T cells secreted IL-4, but not IL-2, IFN
      gamma, or TNF-beta, in response to the autologous melanoma cells, suggesting that
      they belong to the Th2 subtype. Their cytotoxicity was directed against the IFN
      gamma-transduced melanoma cells and was HLA-DR-restricted. The autologous and two
      allogeneic IFN-gamma-modified melanoma cell lines shared melanoma antigen(s)
      presented in the context of HLA-DR15. HLA-DR15(+) nonmelanoma cells were
      resistant targets indicating that the shared antigen(s) is melanoma associated.
      Parental autologous and HLA-DR-matched allogeneic melanoma cell lines, displaying
      low levels of HLA-DR antigens, induced Th2 proliferation and cytokine release,
      but were insensitive to lysis prior to upregulation of HLA-DR and Fas antigens by
      IFN-gamma. Cytolysis was inhibited by anti-HLA-DR and by anti-Fas antibodies,
      suggesting that the cytolysis is mediated via the Fas pathway. While small
      amounts of HLA-DR15 molecules on melanoma cells are sufficient for Th2
      proliferation and cytokine release, higher amounts of HLA-DR15 and the expression
      of Fas are required for CD4(+)-mediated lysis.

PMID- 11520077
TI  - IL-18-induced expression of intercellular adhesion molecule-1 in human monocytes:
      involvement in IL-12 and IFN-gamma production in PBMC.
AB  - IL-18 time- and concentration-dependently upregulated the expression of
      intercellular adhesion molecule-1 (ICAM-1) in a monocyte population in human PBMC
      as determined by FACS analysis while the expression of CD11a, CD18, CD29, CD44,
      and CD62L in monocytes and that of ICAM-1, CD11a, CD18, CD29, CD44, and CD62L in
      T cells was not influenced by IL-18. IL-18 in the same concentration range
      stimulated the production of IL-12, TNF-alpha, and IFN-gamma in culture of PBMC;
      however, IL-18-induced expression of ICAM-1 in monocytes was not inhibited by
      anti-IL-12, anti-TNF-alpha, or anti-IFN-gamma Ab, suggesting the independence of
      the upregulating effect of IL-18 on endogenous IL-12, TNF-alpha, and IFN-gamma
      production. IL-18 also induced the aggregation of PBMC, which was prevented by
      anti-ICAM-1 and anti-LFA-1 Abs. On the other hand, anti-ICAM-1 and anti-LFA-1 Abs
      inhibited IL-18-induced production of three cytokines, IL-12, IFN-gamma, and TNF
      alpha, by 60 and 40%, respectively. These results strongly suggested that the IL
      18-induced upregulation of ICAM-1 and the subsequent adhesive interaction through
      ICAM-1 on monocytes and LFA-1 on T/NK cells generate an additional stimulatory
      signaling as well as an efficient paracrine environment for the IL-18-initiated
      cytokine cascade.

PMID- 11520078
TI  - Interleukin-2 activates human peripheral blood eosinophils.
AB  - The effect of interleukin (IL)-2 on eosinophil survival and mediator release was
      investigated in vitro. Human peripheral blood eosinophils were isolated and
      purified from mildly atopic donors and cultured on albumin-coated wells with
      different concentrations of IL-2, interferon (IFN)-gamma, and granulocyte
      macrophage colony stimulating factor (GM-CSF) and their viability was evaluated
      after 4 days in culture. Eosinophils were cultured with IL-2 (1000 u/ml), IFN
      gamma (1000 u/ml), or GM-CSF (10 ng/ml) for 18 h, or with platelet activating
      factor (PAF) (10(-6) M) for 20 min, and the release of eosinophil peroxidase
      (EPO) and IL-6 was measured. Nedocromil sodium (10(-5) M) was added with each of
      the above cytokines to study the inhibitory effect of this drug on EPO release. A
      significant increase of EPO release was induced by IL-2, IFN-gamma, and GM-CSF
      after 18 h in culture. IL-2 as well as IFN-gamma induced a significant IL-6
      release from eosinophils. Nedocromil sodium significantly inhibited EPO release
      from eosinophils induced by IL-2 or PAF. These results show that IL-2 can
      activate peripheral blood eosinophils to release granule mediators (EPO) and
      cytokines (IL-6). Taken together with the presence of IL-2 receptors on
      eosinophils, we conclude that IL-2 is an important mediator in allergic
      inflammation and a possible target for pharmacological modulation.

PMID- 11520079
TI  - Failure to expand influenza and tetanus toxoid memory T cells in vitro correlates
      with disease course in SIV infected rhesus macaques.
AB  - Marked decreases in influenza (flu) and tetanus toxoid (T.T.) antigen specific
      CD8(+) and CD4(+) T cell memory responses were noted shortly after SIV infection
      in monkeys that go on to develop clinical disease within 18 months (normal
      progressor, NP) following SIV infection but not in monkeys that remain
      asymptomatic >3 years post SIV infection (long-term nonprogressor, LTNP). While
      PBMCs from NP and LTNP monkeys demonstrate both low and high avidity flu and T.T.
      specific CD8(+) and CD4(+)T cell immune responses prior to SIV infection, the
      PBMCs from NP but not LTNP fail to generate high avidity T cell responses post
      SIV infection. This failure to generate high avidity T cell responses in vitro
      correlated with increased apoptotic cell death in PBMC cultures from NP animals.
      Since high avidity antigen specific CTLs have been shown to be most efficient in
      eliminating viral infections, the present finding has important implications for
      the evaluation of the level of immune reconstitution following various modalities
      of therapy in HIV-1 infected patients.

PMID- 11520080
TI  - Intracellular transport of MHC class II and associated invariant chain in antigen
      presenting cells from AP-3-deficient mocha mice.
AB  - MHC class II-restricted antigen presentation requires trafficking of newly
      synthesized class II-invariant chain complexes from the trans-Golgi network to
      endosomal, peptide-loading compartments. This transport is mediated by dileucine
      like motifs within the cytosolic tail of the invariant chain. Although these
      signals have been well characterized, the cytosolic proteins that interact with
      these dileucine signals and mediate Golgi sorting and endosomal transport have
      not been identified. Recently, an adaptor complex, AP-3, has been identified that
      interacts with dileucine motifs and mediates endosomal/lysosomal transport in
      yeast, Drosophila, and mammals. In this report, we have assessed class II
      invariant chain trafficking in a strain of mice (mocha) which lacks expression of
      AP-3. Our studies demonstrate that the lack of AP-3 does not affect the kinetics
      of invariant chain degradation, the route of class II-invariant chain transport,
      or the rate and extent of class II-peptide binding as assessed by the generation
      of SDS-stable dimers. The possible role of other known or unknown adaptor
      complexes in class II-invariant chain transport is discussed.

PMID- 11520081
TI  - What constitutes good practice in surgical oncology?

PMID- 11520082
TI  - Nipple-sparing mastectomy in breast cancer: a viable option?
AB  - BACKGROUND: In women with breast cancer for whom breast-conserving therapy (BCT)
      is not the best option, a nipple and areola complex-(NAC) sparing mastectomy with
      immediate reconstruction has been proposed as a good and safe alternative to
      conventional, more radical mastectomy. Surgeons hesitate to perform this
      operation for fear of recurrence of tumour in the NAC due to undetected nipple
      involvement (NI) of the tumour. In order to determine whether a NAC-sparing
      mastectomy is a viable option, the frequency and predictive factors of NI by the
      tumour were studied in the literature. METHODS: A literature survey was performed
      by searching the Medline database. Other references were derived from the
      material perused. RESULTS AND CONCLUSIONS: NI is found in up to 58% of mastectomy
      specimens and correlates with tumour size, tumour-areola or tumour-nipple
      distance, positive lymph nodes and clinical suspicion. Best candidates for NAC
      sparing mastectomy are patients with a small tumour (T1) at a large distance (>4
      5 cm) from the nipple. However, in these patients BCT has excellent results with
      low complications and recurrence rates. Considering the incidence of NI in larger
      tumours (T2 average 33%, T3 average >50%) a NAC-sparing mastectomy may carry an
      unacceptable high risk for local relapse and should therefore not be advocated.

PMID- 11520083
TI  - The prognostic significance of CD44s and CD44v6 expression in stage two breast
      carcinoma: an immunohistochemical study.
AB  - AIMS: Expression of the v6 variant isoform of CD44 has been causally associated
      with the development of metastases. This study, using immunohistochemical
      techniques, examined the prognostic significance of CD44s and CD44v6 expression.
      METHODS: A cohort of 109 women presenting with stage 2 breast cancer, with a
      minimum follow-up of 5 years, were assessed. RESULTS: Eighty percent of patients
      demonstrated CD44v6 expression on immunohistochemical studies. CD44v6 expression
      in tissue sections was found to be independent of age, tumour size, grade, and
      lymph-node status. No significant association was demonstrated between CD44v6
      expression and either disease-free or overall survival. Similar findings were
      observed for CD44s. CONCLUSIONS: CD44s and CD44v6 do not appear to be useful as
      prognostic indicators in early breast cancer. The increased expression of variant
      CD44 isoforms seen in breast neoplasia may merely be a marker for loss of control
      of alternative splicing within tumour tissue.

PMID- 11520084
TI  - Sentinel lymph-node biopsy-based prediction of further breast cancer metastases
      in the axilla.
AB  - BACKGROUND: Histopathological factors may help identifying a subgroup of breast
      cancer patients with metastases confined to the sentinel lymph nodes (SLNs).
      METHODS: A retrospective analysis was carried out on 111 tumours successfully
      mapped with Patent blue, 69 of which had SLN metastases. RESULTS: Multivariate
      analysis revealed that SLN metastases situated in the sinuses and a small tumour
      size are the two most important predictors of involvement of only one SLN. The
      metastasis size and a small tumour size were found important in the model
      discriminating between tumours with metastases to SLNs only and those with non
      SLN involvement. Classification of tumours with only one SLN metastasis and those
      with a multinodal involvement resulted in a smaller error rate, falsely
      classified as lesser nodal involvement. Patients with tumours <1.8 cm and
      metastatic to the sinuses of a single SLN had a low probability of non-SLN
      metastasis, and might be candidates for axillary sparing after a positive SLN
      biopsy. CONCLUSIONS: Further investigations are required to assess the validity
      of such predictive models for the identification of patients with no metastases
      beyond the SLN. Axillary treatment must remain the rule until predictive models
      of non-SLN involvement are fully validated.

PMID- 11520085
TI  - Breast mass removal made easy by the lump extractor: introducing a new instrument
      in breast surgery.
AB  - The difficulty encountered in the removal of breast lumps has been addressed by
      the use of a new instrument. The lump extractor described in this paper allows
      minimal scar surgery and prevents crushing of the breast mass.

PMID- 11520086
TI  - The needs of general practitioners in the follow-up of patients with colorectal
      cancer.
AB  - BACKGROUND: Follow-up of colorectal cancer creates a large workload for National
      Health Service (NHS) clinics. We investigated what the requirements of the
      general practitioners of Teesside, UK would be in order to accept to participate
      in the follow-up of colorectal cancer. MATERIALS AND METHODS: Postal survey
      questionnaire of all 278 GPs in 83 practices under Tees Health Authority, UK.
      RESULTS: The response rate was 59%. Forty three percent of GPs thought it would
      be a natural part of their work while 39% thought it was not their remit and
      fifty percent found the idea interesting, 37% thought it unrealistic and 8%
      considered it wrong. Their main reservations were work burden (60%), lack of
      guidelines (59%), lack of specialized knowledge (51%) and delays of re-referrals
      to specialists (41%). Their principal requirements in order to participate were
      guidelines (77%), fast routes of re-referral to specialists (72%), seminars to
      bring them up-to-date (50%) and open access to investigations such as colonoscopy
      (45%). From the respondents, 56% were keen to participate in further discussion
      on the issue. CONCLUSION: A significant number of general practitioners wish to
      participate in the follow-up of colorectal cancer. Their principal requirements
      concern quality issues, including guidelines, up-to-date knowledge and delays in
      re-referring patients with recurrence.

PMID- 11520087
TI  - Immunohistochemical localization of group II phospholipase A2 in the tumours and
      mucosa of the colon and rectum.
AB  - BACKGROUND: Group II phospholipase A(2)(PLA(2)) is an enzyme important in
      malignant transformation and in the invasion process of malignant cells. The aim
      of the present study was to investigate the expression of group II PLA(2)in the
      cancers of the colorectum, peritumoural mucosa and in the mucosa distant from the
      tumour. METHODS: Resection specimens from 57 patients with colorectal carcinoma
      (caecum 10, ascending 10, transverse 10, sigmoid colon nine, and rectum 18) were
      analysed immunohistochemically. Histological slides from paraffin blocks were
      stained by the human monoclonal group II PLA(2)antibody ('Upstate Biotechnology',
      Lake Placid, NY 12946, USA. Antibody Class: IgG1k. Immunogen: HPC purifed human
      sperm phospholipase A(2)- 14 kDa enzyme) using the standard DAKO peroxidase
      labelled streptavidin-biotin method by TechMate 500 stainer. Group II
      PLA(2)expression was evaluated semi-quantitatively according to the extensivity
      and intensivity of the positive cells. For statistical evaluation the Kruskal
      Wallis one way analysis of variance on ranks and the Mann-Whitney rank sum tests
      were used. RESULTS: The highest expression of group II PLA(2)was found in the
      peritumoural mucosa (median 4.00), much lower in the mucosa distal from the
      tumour (median 0.70) and almost no activity in the tumour itself (median 0.00),
      all differences were statistically significant (all pairwise multiple comparison
      procedures - Dunn's Method P<0.05). The expression of group II PLA(2)was higher
      in the left colon and rectum than in the right colon (Mann-Whitney rank sum test
      P<0.05). CONCLUSIONS: Our results suggest that there is variation of the group II
      PLA(2)expression throughout the mucosa and tumours of the colorectum, which might
      reflect the progression of neoplastic process.

PMID- 11520088
TI  - Survival after pancreaticoduodenectomy for periampullary adenocarcinoma: an
      update.
AB  - AIM: Survival after pancreaticoduodenectomy for periampullary tumours is limited.
      Over the last decade peri-operative management has improved and morbidity and
      mortality decreased. The aim of the study was to analyse recent survival data
      after pancreaticoduodenectomy and to determine factors that influence survival.
      METHODS: From October 1992 to September 1998, 204 patients with a ductal
      adenocarcinoma in the pancreatic head (108), distal bile duct (32), and ampulla
      (64) who underwent standard pancreaticoduodenectomy, were analysed with regard to
      histology and tumour status. Survival was calculated by using the Kaplan-Meier
      method. Risk factors were identified in a univariate and multivariate analysis.
      RESULTS: Median survival after resection for carcinoma of the pancreatic head,
      distal bile duct, and ampulla were 16, 25 and 24 months, respectively (P=0.008).
      In the univariate analysis vein resection, blood transfusion of more than four
      packed red cells, the presence of tumour positive resection margins, lymph-node
      metastases and poor tumour differentiation significantly decreased survival. In
      the multivariate analysis positive resection margins, lymph-node metastases, and
      poor tumour differentiation independently influenced survival. CONCLUSIONS:
      Resection margins, lymph-node status and tumour differentiation are independent
      prognostic factors. Survival after standard pancreaticoduodenectomy for
      periampullary tumours has not improved.

PMID- 11520089
TI  - Nutritional and life-quality consequences of aboral pouch construction after
      total gastrectomy: a randomized, controlled study.
AB  - AIMS: The aboral pouch, a new type of gastric substitute, has been introduced
      after total gastrectomy and compared to simple Roux-en-Y reconstruction in a
      prospective, randomized study. Anthropometric data, serum nutritional parameters,
      small intestinal passage, lipid and carbohydrate absorption and quality of life
      were measured 6 and 12 months after total gastrectomy. PATIENTS AND METHODS:
      Between September 1997 and April 2000 46 patients entered the study, 24 to the
      aboral pouch group and 22 to the control, simple Roux-en-Y group. RESULTS:
      Interim analysis of the data revealed significantly higher serum cholesterol
      levels, better lipid absorption and quality of life in patients who underwent
      aboral pouch construction. CONCLUSION: Aboral pouch construction is a feasible
      reconstruction method after total gastrectomy providing better lipid absorption
      and quality of life for patients after total gastrectomy.

PMID- 11520090
TI  - Locoregional recurrence of retroperitoneal soft tissue sarcoma: second chance of
      cure for selected patients.
AB  - BACKGROUND: Locoregional recurrence of a retroperitoneal soft tissue sarcoma
      (RSTS) may offer a second chance of curative surgical treatment. In a population
      based study the proportion of patients developing isolated locoregional
      recurrences (LR) was determined and the outcome of these patients was analysed.
      METHOD: In a retrospective nationwide study, data were collected on 142 patients
      treated between 1 January 1989 and 1 January 1994 for primary RSTS. In patients
      who had been treated radically for their primary sarcoma (77/142, 54%), the
      pattern of recurrence was evaluated. Factors predictive of survival for patients
      with LR were studied. RESULTS: After a median follow-up of 86 (range 60-101)
      months, 32 patients (42%) had developed LR, and distant metastasis (DM) had been
      diagnosed in 17 patients (22%). Median disease-free interval between the initial
      operation and the establishment of LR or DM was 22 and 19 months, respectively.
      Five-year cumulative survival of patients with established LR was 37% in
      comparison with 11% for patients with DM (P=0.062). Factors predictive of
      favourable outcome in patients with LR were the absence of multifocal recurrence
      (n=13 P=0.01), lipomatous histomorphology (n=20 P=0.02), and a complete resection
      of recurrent sarcoma (n=17 P=0.04). CONCLUSION: After a median follow-up of 7
      years following radical treatment of a primary RSTS, 42% of the patients had
      developed isolated locoregional recurrences. A complete resection of recurrent
      disease, lipomatous histomorphology and the absence of multifocal growth
      influenced prognosis favourably.

PMID- 11520091
TI  - A long-term review of the treatment of patients with Ewing's sarcoma in one
      institution.
AB  - AIMS: The treatment of patients suffering from Ewing's sarcoma has changed over
      the last three decades. We report the analyses, significant prognostic factors,
      interdisciplinary approach and development of therapy in one institution in
      Austria. METHODS: One hundred and forty-two patients treated for Ewing's sarcoma
      between 1949 and 1994 were reviewed. Median follow-up was 8.5 years. Fifty-six
      patients were treated between 1949 and 1980 (group 1), and 86 patients between
      1981 and 1994 (group 2). Patients in group 1 were treated with polychemotherapy.
      Patients in group 2 were treated with a neoadjuvant CESS (Cooperative Ewing's
      Sarcoma Study) regimen. In group 1, 24 patients underwent biopsy only, 32
      patients had a definitive operation, 48 patients received either radiation
      therapy only or additional radiation therapy compared with in group 2: 6, 80 and
      44 cases, respectively. RESULTS: Five-year overall survival (OS) increased from
      27% to 57%. Significant prognostic factors for OS were pre-operative metastases
      (P=0.0001), tumour location (P=0.0048), type of chemotherapy (P=0.002) and
      response to chemotherapy (P=0.0004). Chemotherapy (P=0.037), tumour location
      (P=0.0017) and metastases at diagnosis (P=0.0025) were significant. CONCLUSION:
      The most effective treatment of Ewing's sarcoma is chemotherapy.

PMID- 11520092
TI  - Prognostic significance of p53, bax and bcl-2 gene expression in patients with
      laryngeal carcinoma.
AB  - AIM: This study was designed to examine the prognostic significance of the
      coexpression of three genes (bax, bcl-2 and p53) which play a critical role in
      the apoptotic mechanisms in patients with squamous cell laryngeal carcinoma.
      MATERIALS AND METHODS: The immunohistochemical expression of bcl-2, bax and p53
      genes was retrospectively examined in 38 patients with squamous cell laryngeal
      carcinoma and in five controls (necrotomic tissue). Tissue specimens were
      obtained both during the diagnostic biopsy and at the time of surgery.
      Clinicopathological and survival data were correlated with the staining results.
      RESULTS: Bcl-2 protein expression (P=0.0472), stage (P=0.0087) and lymph-node
      involvement (P=0.0488) were found to be independent prognostic factors. Increased
      bcl-2 protein expression correlated with a better 5-year survival (P=0.0472).
      Patients who were bcl-2(-)/p53(-) (n=25) or bax(+)/bcl-2(-) (n=13) had a
      significantly worse overall survival (P=0.0305 and P=0.0482, respectively).
      Similarly, patients who were bax(+)/bcl-2(-)/p53(-) (n=11) also had a worse 5
      year survival compared with the rest of the group (P=0.0088). Changes that were
      noticed in bax and p53 protein expression from the time of biopsy until the time
      of surgery did not correlate with a significant increase in the overall survival.
      CONCLUSIONS: The expression of bcl-2 gene appears to be an independent prognostic
      factor for patients with laryngeal carcinoma. The coexpression of the genes
      studied can be used to determine aggressive clinical phenotypes.

PMID- 11520093
TI  - Tracheal reconstruction under tension: an experimental study in sheep.
AB  - AIMS: Invasion of the trachea by thyroid cancer is a difficult problem.
      Circumferential resection and end-to-end reconstruction is the treatment of
      choice. The objective of our study was to investigate the effect of tension on
      tracheal healing and stenosis formation, and to ascertain the maximum tolerable
      tension. METHODS: Tracheal resections of 3, 6 and 9 cm with end-to-end
      anastomosis were performed on 25 sheep. The intraoperative force required for
      approximation of the tracheal stumps was measured. Luminal stenosis was
      determined with the aid of computerized planimetry 1, 2, 4, 8 and 24 weeks post
      operatively. RESULTS: A gradual increase of the stenosis rate occurred with
      increasing tension on the anastomosis. Acceptable results were achieved in the
      majority of cases without release techniques or tension suture. CONCLUSIONS:
      Tracheal anastomosis under tension does not always lead to disruption or
      separation of the anastomosis. With the additional use of release manoeuvres and
      tension sutures, tracheal anastomosis under tension are possible without severe
      stenosis. The additional use of temporary stenting needs to be elucidated.

PMID- 11520094
TI  - Referrals for second opinion in surgical pathology: implications for management
      of cancer patients in the UK.
AB  - OBJECTIVE: To compare patterns of outgoing referral practice from one large
      district general hospital histopathology (cellular pathology) laboratory to other
      pathology laboratories. DESIGN: Referral cases for the relevant years were
      identified via hand searching of consultant referral files and from a central
      laboratory referral file. A comparison was made of the number and nature of
      pathology case referrals made to other laboratories in year 1990 with those made
      in year 1998. SETTING: Large district general hospital pathology laboratory in
      the UK. RESULTS: A statistically significant increase in the number of cases
      referred for a second opinion to an outside pathologist was noted, from 60 to 128
      cases, representing an increase from 0.35 to 0.56% of total laboratory specimen
      workload (P=0.0034). In 36 (31.0%) of 116 cases from 1998 the diagnosis was
      altered, or a confident diagnosis was made where previously there was no definite
      diagnosis. Five cases with a benign in-house diagnosis had a malignant second
      opinion diagnosis and five cases with a malignant in-house diagnosis had a benign
      second opinion diagnosis. The largest single category of referred cases was for
      classification/grading of malignant lymphoma, comprising 27 (23%) of cases. The
      mean time delay between receipt of a specimen in the laboratory and issuing of
      the final report was 22 days (range 7-60 days). Only 25% of the referred cases
      were reported within 14 days. CONCLUSIONS: Referrals are an important component
      of pathology practice. In the UK much of this activity is performed on a 'grace
      and favour' basis between laboratories despite the fact that referral cases are
      often complex and time consuming for the recipient pathologist and laboratory.
      Histopathology referrals do not seem to be adequately costed and accounted for in
      interinstitutional service level agreements within the UK National Health
      Service.

PMID- 11520095
TI  - New drugs and combinations in the palliative treatment of colon and rectal
      cancer.
AB  - Colorectal cancer (CRC) is a common disease. The overall survival has improved
      only marginally in recent decades despite advances in surgery and early
      detection. Potentially curative resection at disease presentation can be
      performed only in 70-80% of the patients, and overall survival at 5 years is less
      than 60%. Advanced disease is associated with a poor prognosis. Treatment for
      advanced colorectal cancer has nevertheless made progress in the last few years.
      Systemic chemotherapy doubles the survival of these patients compared to
      untreated controls. Chemotherapy has demonstrated effective palliation,
      improvement of quality of life (QoL) and symptom improvement in such patients.
      For nearly four decades, fluorouracil (5FU) has been the mainstay of treatment.
      New compounds active against colorectal cancer are now available. Several studies
      on this topic are ongoing.

PMID- 11520096
TI  - The peri-areolar incision--gateway to the breast!
AB  - BACKGROUND: In breast surgery the challenge for good cosmesis needs to be met in
      the management of benign or malignant disease. With tumours this must be balanced
      against good clearance with safe and adequate margins. For excision of benign
      lesions obvious deforming scars are unacceptable while with breast preserving
      cancer surgery a badly placed scar reduces reconstructive choices. The peri
      areolar incision has a role in skin sparing mastectomy (SSM) and in breast
      conserving surgery. This paper describes the application of this incision in
      breast surgery. METHODS: Patients undergoing breast surgery for benign and
      malignant disease have undergone operations using a peri-areolar incision.
      Examples of use of this incision are shown. CONCLUSION: The peri-areolar incision
      provides good cosmesis while allowing for future or immediate reconstruction and
      without reducing the range of options.

PMID- 11520097
TI  - Breast cancer, Cowden disease and PTEN-MATCHS syndrome.

PMID- 11520098
TI  - Paraneoplastic cerebellar degeneration: an unusual presentation of breast
      carcinoma.

PMID- 11520099
TI  - Primary anterior urethral transitional cell carcinoma: a rare tumour.

PMID- 11520101
TI  - Grading of infiltrating lobular carcinoma.

PMID- 11520102
TI  - Anaphylaxis to patent blue dye during sentinel lymph node biopsy for breast
      cancer.

PMID- 11520103
TI  - Epithelial mucins of the ocular surface: structure, biosynthesis and function.

PMID- 11520104
TI  - Regeneration of rabbit cornea following excimer laser photorefractive
      keratectomy: a study on gap junctions, epithelial junctions and epidermal growth
      factor receptor expression in correlation with cell proliferation.
AB  - Corneal wound repair was investigated in rabbits following excimer laser ablation
      of a 6 mm diameter and 90 microm deep disc. In the healing process particular
      attention was focused on the epithelium where gap junction expression and the
      rearrangement of desmosomes and hemidesmosomes were correlated with cell
      proliferation and epidermal growth factor receptor expression. Immunofluorescence
      based confocal laser scanning microscopy, semithin resin section morphology and
      electron microscopy were utilized. In resting cornea two isotypes of gap
      junctions, confined to different regions in the same basal epithelial cells, were
      detected. Particulate connexin43 (alpha1) immunostaining was concentrated on the
      apical while the connexin26 type (beta2) in the baso-lateral cell membranes. This
      is the first report of connexin26 in the cornea. Connexin43 was found also in
      corneal keratocytes and endothelial cell. Since the two connexins do not form
      functioning heteromeric channels and have selective permeabilities they may serve
      alternative pathways for direct cell-cell communication in the basal cell layer.
      During regeneration both connexins were expressed throughout the corneal
      epithelium including the migrating cells. They also showed transient up
      regulation 24 hr after wounding in the form of overlapping relocation to the
      upper cell layers. At this time, basal epithelial cells at the limbal region,
      adjacent to the wound and those migrating over the wounded area all expressed
      membrane bound epidermal growth factor receptor and they were highly
      proliferating. In conclusion, like in other stratified epithelia connexin26 is
      also expressed in the cornea. Transient up-regulation and relocation of connexins
      within the regenerating epithelium may reflect the involvement of direct cell
      cell communication in corneal wound healing. Mitotic activity in the migrating
      corneal epithelial cells is also a novel finding which is probably the sign of
      the excessive demand for new epithelial cells in larger wounds not met alone by
      the proliferating limbal stock.

PMID- 11520105
TI  - Microdialysis measurement of ascorbic acid in rabbit vitreous after photodynamic
      reaction.
AB  - A method for long-term intravitreous microdialysis was used to measure endogenous
      reduced ascorbic acid in the vitreous of rabbits by HPLC-ECD before and after
      exposure to intense visible light in the presence of fluorescein. Cellulose
      microdialysis probes were implanted into the vitreous humor of each eye and after
      stabilization ascorbic acid measurements were recorded over a 14 day period.
      Under this experimental condition, normal ascorbic acid concentrations in
      vitreous varied from 98.0 +/- 9.8 to 106.9 +/- 20.3 microM(mean +/- S.D.). The
      eyes received light irradiation (25 000 lux) for 2 hr and fluorescein was used as
      the photosensitizer once or twice. No immediate effects on ascorbic acid
      concentrations could be observed in the eyes irradiated twice without fluorescein
      i.v. injections and in the twice fluorescein injected without irradiation.
      However, in the eyes irradiated once with fluorescein (30 mg kg(-1)), ascorbic
      acid concentration after irradiation significantly decreased from day 2 and
      continued over a period of 10 days compared with that before irradiation and
      maximal reduction was 32.6% (P < 0.005) on day 6 after irradiation. By day 13,
      the ascorbic acid concentration returned to control levels (P > 0.01). In the
      eyes irradiated twice with fluorescein injections, ascorbic acid concentration
      after irradiation decreased even more over the experimental period and the
      maximal reduction was 65.5% (P < 0.005) on day 5 after irradiation and did not
      recover over the next 9 days. In the eyes irradiated twice with fluorescein
      injections plus administration of ascorbic acid (150 mg kg(-1)) 30 min before
      irradiation, a significant increase (52.5%) of ascorbic acid (P < 0.005) was
      found on day 1 and control levels of ascorbic acid were maintained from day 2
      onward. The protective role of ascorbic acid in the vitreous humor against
      photodynamic reaction is suggested.

PMID- 11520106
TI  - Effect of glutamate analogues on red-green opponent interaction in monkey
      electroretinograms.
AB  - The effect of glutamate analogues on red-green opponent interaction was
      electrophysiologically investigated in anesthetized cynomolgus monkeys (Macaca
      fascicularis). Two approaches were employed: amplitude measurement and principal
      component analysis. Electroretinograms were recorded for 23 monochromatic stimuli
      (400-700 nm) at an equal energy with white light adaptation before and after
      treatment with the glutamate analogues, 2-amino-4-phosphonobutyric acid, cis -2,3
      piperidine-dicarboxylic acid, or both. Before treatment, although spectral
      amplitude curves of the a- and d-waves showed single, broad peaks at about 550
      nm, the b-wave curve had three peaks at about 460, 540 and 600 nm, indicating the
      occurrence of the red-green opponent interaction. Principal component analysis
      performed on these waveforms extracted three components with short, middle, and
      long wavelength peaks, well defined characteristics of the red-green opponency.
      After vitreal injection of 2-amino-4-phosphonobutyric acid, the a- and d-wave
      amplitudes were enhanced while the b-wave amplitude was almost completely
      diminished. However, principal component analysis showed basically similar
      characteristics to those before drug, suggesting that the red-green opponency was
      not affected. In contrast, after application of cis -2,3-piperidine-dicarboxylic
      acid, the a- and d-waves were diminished and the b-wave was enhanced as expected,
      however the enhancement was observed only in the short and middle wavelengths. As
      a result of this partial enhancement, the b-wave spectral amplitude curve showed
      only a single peak, unlike in the control. In addition, principal component
      analysis revealed a quite different result from the control; only two components
      with short and middle wavelength peaks and the component with long wavelength
      peak disappeared. Similar two components were also separated after the
      conjunction of both drugs. These results demonstrate that red-green opponency is
      greatly inhibited by cis -2,3 piperidine-dicarboxylic acid, and thus suggest that
      horizontal cells are related to a generation of the red-green opponency through a
      cone type selective or nonselective negative feedback.

PMID- 11520107
TI  - Association behaviour of human betaB1-crystallin and its truncated forms.
AB  - betaB1-crystallin plays an important role in the assembly of betaH-crystallin yet
      is known to be subject to N-terminal sequence truncations during human lens
      development and ageing. Here we have over-expressed human betaB1-crystallin, and
      various truncated forms in Escherichia coli and used mass spectrometry to monitor
      the monomer molecular weight. Gel permeation chromatography and laser light
      scattering have been used to estimate the assembly size of the various
      polypeptides as a function of protein concentration. The full-length betaB1
      crystallin behaves as a dimer, like recombinant human betaB2-crystallin, but
      undergoes further self-association at high protein concentrations, unlike the
      betaB2-crystallin. Major truncations from the N-terminal extension lead to
      anomalous behaviour on gel permeation chromatography indicative of altered
      interactions with the column matrix, whereas light scattering indicated dimers at
      low protein concentration that self-associate as a function of protein
      concentration. Loss of 41 residues from the N-terminus, equivalent to an in vivo
      truncation site, resulted in temperature-dependent phase separation behaviour of
      the shortened betaB1-crystallin. Good crystals have been grown of a truncated
      version of human betaB1-crystallin using an in vitro cleavage protocol.

PMID- 11520108
TI  - Immunohistochemical studies of the retina following long-term implantation with
      subretinal microphotodiode arrays.
AB  - This study evaluates the feline retina following surgical placement of a
      semiconductor-based microphotodiode array (MPA) into the subretinal space. Post
      operative evaluations of implant durability and clinical biocompatibility have
      been carried out in these animals. Here, we examine the integrity of the
      implanted retina using anatomical techniques and immunocytochemical metabolic
      indicators. After appropriate fixation, the retina was divided into strips to
      compare areas directly over the implant versus those adjacent to the implant or
      in the opposite, unimplanted eye. In addition to histological analyses, the
      distribution of glial fibrillary acidic protein (GFAP), Na, K-ATPase, and the
      neurotransmitters (glutamate, glycine, and GABA) was examined using
      immunohistochemistry. Directly above the implant there was a near-complete loss
      of photoreceptor outer and inner segments and the outer nuclear layer. In
      comparison, the retina immediately adjacent to the implant appeared normal. In
      the inner nuclear layer overlying the implant, some cellular disorganization was
      present, however, the content was not significantly reduced. Also GFAP was up
      regulated in the Muller cells directly overlying the MPA, but the retina adjacent
      to the implant showed a normal distribution of GFAP in the astrocytes located in
      the ganglion cell layer. The distributions of Na, K-ATPase adjacent to and
      overlying the implant were not different. Glutamate showed a decrease in overall
      labeling, but no change in the inner retinal layers. Glycine was found to be up
      regulated in the inner nuclear layer immediately overlying the implant, while
      GABA showed decreased labeling over the MPA. Since photoreceptors overlying the
      implant degenerate, we compared the changes observed in the implanted retina to
      those in the Abyssinian cat model of photoreceptor degeneration. Generally, the
      retinal changes observed over the implant were similar to those seen in the
      Abyssinian cat, indicating that they may be associated with photoreceptor
      degeneration. Future studies will concentrate on MPAs designed to improve
      circulation to the outer retina which may decrease cell loss.

PMID- 11520109
TI  - An extensive system of extravascular smooth muscle cells exists in the choroid of
      the rabbit eye.
AB  - We investigated the structural organization of the choroid especially with regard
      to the presence of extravascular smooth muscle (EVSM) cells in albino rabbits.
      The eyes were fixed by intracardiac perfusion and processed for light, confocal,
      and electron microscopy. An unlabeled monoclonal antibody against alpha-actin of
      smooth muscle and a horseradish-peroxidase-conjugated secondary antibody were
      used for immunodetection of smooth muscle actin by light microscopy. For confocal
      microscopy, whole mount choroids were immunostained with a fluorescein
      isothiocyanate-conjugated (FITC) antibody. Our investigations revealed that the
      choroidal vessels are enveloped by bundles of EVSM. In contrast to the circular
      orientation of the smooth muscle cells of the tunica media of the choroidal
      vessels, the cells of the EVSM system were oriented longitudinally along the
      external surface of the vessel wall. The EVSM cells were strongly immunopositive
      for smooth muscle alpha-actin and exhibited a green fluorescence of the FITC
      labeled anti-alpha-actin antibody. Individual cells were elongated and spindle
      shaped, had the usual ultrastructural features of smooth muscle cells and, in
      places, were organized as 20 layers. EVSM cells were present throughout the
      thickness of the choroid, but not between the fenestrated endothelial lining of
      the choriocapillaris and Bruch's membrane, and extended from the optic nerve to
      the ciliary body where they merged with the ciliary muscles. Based on the three
      dimensional organization, immunoreactivity, and cellular and subcellular features
      of the EVSM system as well as information in the literature, we hypothesize that,
      functionally, this system, in conjunction with the choroidal vasculature,
      contributes to the myogenic control of choroidal blood flow and tissue volume,
      and also affects the intraocular pressure as well as the refractive and
      accommodative state of the eye.

PMID- 11520110
TI  - Effects of nitric oxide synthase inhibition on ciliary blood flow, aqueous
      production and intraocular pressure.
AB  - A prior study found that inhibition of nitric oxide synthase with L-NAME causes a
      large, rapid decrease in IOP in anesthetized rabbits. In this follow-up study we
      sought to determine if this hypotensive effect was due to decreased aqueous
      production, possibly caused by ciliary vasoconstriction. Two protocols were
      performed in anesthetized rabbits. In the first protocol, mean arterial pressure
      (MAP) and IOP were measured by direct cannulation, and aqueous flow was measured
      by fluorophotometry, before and after L-NAME (5 mg kg(-1), i.v., n = 7). In the
      second protocol, ciliary blood flow was measured transclerally by laser Doppler
      flowmetry while MAP was varied mechanically over a wide range before and after L
      NAME (5 mg kg(-1), i.v., n = 8). L-NAME caused a significant increase in MAP and
      decreases in IOP, ciliary blood flow and aqueous flow. L-NAME also caused a
      significant downward shift in the ciliary pressure-flow relation over the entire
      pressure range examined. The results indicate that L-NAME causes ciliary
      vasoconstriction and decreases aqueous production, suggesting that the L-NAME
      ocular hypotensive effect may be due in part to a blood flow-dependent decrease
      in aqueous production. However, assuming no uveoscleral outflow and constant
      episcleral venous pressure and outflow facility, the decrease in aqueous flow
      accounts for 66% of the drop in IOP, suggesting an additional effect of L-NAME on
      aqueous outflow.

PMID- 11520111
TI  - Intracellular Ca(2+) changes induced by in vitro ischemia in rat retinal slices.
AB  - The effect of ischemia on intracellular Ca(2+)concentration [[Ca(2+)](i)] in
      retinal slices was investigated. [Ca(2+)](i)in each layer of the retina was
      determined from fluorescence images in rat retinal slices loaded with fura2-AM.
      Ischemic like conditions were imposed on the retinal slice in vitro by perfusion
      with an oxygen/glucose deprived solution. All measurements were taken at 25
      degrees C except when temperature dependence was examined. In response to 100 m M
      K(+)or 0.2 m M glutamate under normoxic conditions, the [Ca(2+)](i)increase was
      higher in the inner retinal layers. Fifteen min ischemia evoked an increase in
      Ca(2+)levels in all layers of the retina, and the rates of increase were
      especially high in the outer/inner segment layer and the outer nuclear layer.
      Ischemia in the absence of extracellular Ca(2+)also induced a Ca(2+)rise, but at
      lower rates than with standard ischemia. Intermittent ischemia, composed of three
      15 min bursts of ischemia at 10 min intervals, promoted the Ca(2+)rise. There was
      a more marked rise in [Ca(2+)](i)when the temperature was increased to 29 or 33
      degrees C. Thus, in the rat retinal slice, in vitro ischemia evoked a more marked
      Ca(2+)rise in the outer retina, which was in contrast to the Ca(2+)responses to
      glutamate or high K(+). The rates of increase in [Ca(2+)](i)with ischemia were
      larger at higher temperatures, and intermittent ischemia also promoted the
      Ca(2+)rise. These increases appear to be derived from predominant influx of
      extracellular Ca(2+)rather than release of intracellular Ca(2+)stores.

PMID- 11520112
TI  - Biochemical and morphological changes during development of sugar cataract in
      Otsuka Long-Evans Tokushima fatty (OLETF) rat.
AB  - The relationship between the polyol pathway and sugar cataracts has been studied
      extensively using streptozotocin-induced diabetic rats and galactose fed rats as
      animal models for insulin-dependent diabetes mellitus (IDDM). In these models,
      sugar cataracts progress quickly, leading to rapid lenticular polyol accumulation
      in the early stages of cataract formation. In 1992, a new animal model of non
      insulin-dependent diabetes mellitus (NIDDM), the Otsuka Long-Evans Tokushima
      Fatty (OLETF) rat, was established. In the present study, we examined both
      biochemical and morphological changes in the lenses of the OLETF rats to
      determine whether these changes reflect those associated with diabetic cataract
      formation and to clarify their relationship with the polyol pathway. For the
      biochemical analysis, we measured the enzyme activity of aldose reductase (AR)
      and sorbitol dehydrogenase (SDH) and the sorbitol levels using 20, 40 and 60 week
      old OLETF or control Long-Evans Tokushima Otsuka (LETO) rats. Enzyme activities
      of AR and SDH, which were lower in 20 week old OLETF rats than in LETO rats, were
      increased in 60 week old OLETF rats. The lenticular sorbitol level of the OLETF
      rats was similar to the control level at 20 weeks of age, but it was markedly
      increased at 40 weeks of age, and slightly decreased at 60 weeks of age compared
      with rats at 40 weeks but not compared with controls. Slight lens fiber swelling
      was observed in the anterior and/or posterior subcapsular regions of 40 week old
      OLETF rats, accompanying elevated sorbitol level and slightly increased SDH
      activity in the lens. Swelling and liquefaction of lens fibers were observed in
      the subcapsular and supranuclear region of 60 week old OLETF rats, as well as
      decreased lenticular sorbitol, and markedly increased SDH activity compared with
      rats at 40 weeks. AR activity was also increased causing the elevation of
      sorbitol in lenses of OLETF rats during the early stages of cataract formation.
      Despite differences in the etiology of diabetes mellitus, the strain of rat and
      the rate of disease progression in the OLETF rat model compared with other
      diabetic models, the present results support the theory that the polyol pathway
      via AR is a factor in the development of sugar cataracts.

PMID- 11520113
TI  - Defects in the MITF(mi/mi) apical surface are associated with a failure of outer
      segment elongation.
AB  - The loss of MITF function in the MITF(mi/mi)mouse affects not only RPE
      differentiation, but also the development of rod photoreceptor outer segments.
      Our data indicate that opsin immunoreactivity is detected in the cell membrane
      and along the ONL/RPE border of developing MITF(mi/mi)rod photoreceptors and that
      rod outer segment morphogenesis is initiated. Although molecules associated with
      the outer segment continued to be expressed, outer segments did not elongate and
      develop stacked organized discs perpendicular to the RPE. The MITF(mi/mi)RPE also
      failed to form apical microvilli and lacked the apical network of the
      phosphoprotein ezrin seen in wild type tissue. The MITF(mi/mi)RPE basal surface
      was loosely organized and retained ezrin labelling which indicated some degree of
      differentiation. The correlation seen in our data suggest that there may be a
      link between the failure of the RPE apical domain to form and lack of rod outer
      segment elongation.

PMID- 11520114
TI  - Antioxidant properties of green and black tea, and their potential ability to
      retard the progression of eye lens cataract.
AB  - Aqueous extracts of green and black tea are shown to quench reactive oxygen
      species such as singlet oxygen, superoxide and hydroxyl radicals, prevent the
      oxidative cross-linking of test proteins and inhibit single strand breakage of
      DNA in whole cells. They are also seen to be able to counteract the oxidative
      insult mounted by cigarette smoke. In rats in which cataract was induced by
      subcutaneous injection of selenite, administration of green or black tea extracts
      led to a retardation of the progression of lens opacity, suggesting the potential
      cataracto-static ability of tea.

PMID- 11520115
TI  - Tumor necrosis factor-alpha and not interleukin-1alpha is the dominant inducer of
      matrix metalloproteinase-9 synthesis in human corneal cells.

PMID- 11520116
TI  - Perforated microelectrode arrays implanted in the regenerating adult central
      nervous system.
AB  - Adult mammalian optic nerve axons are able to regenerate, when provided with the
      permissive environment of an autologous peripheral nerve graft, which is usually
      the sciatic nerve. This study demonstrates the ability of adult rat optic nerve
      axons to regenerate through the preformed perforations of a polyimide electrode
      carrier implanted at the interface between the proximal stump of the cut optic
      nerve and the stump of the peripheral nerve piece used for grafting. Evidence
      that retinal ganglion cells regenerated their axons through the perforated
      electrode carrier was obtained by retrograde labeling with a fluorescent dye
      deposited into the sciatic nerve graft beyond the nerve-carrier-nerve junction.
      The number of regenerating cells could be enhanced by injecting neuroprotective
      drugs like aurintricarboxylic acid and cortisol intravitreally. A second line of
      evidence was obtained by immunohistochemical staining with antibodies to
      neurofilament. Third, electrical activity of the regenerating nerves was recorded
      after stimulating the retina with a flash of light. The results suggest that a
      regenerating central nerve tract may serve as an experimental model to implant
      artificial microdevices to monitor the physiological and topographical properties
      of neurites passing through the device or to stimulate them, thus interfering
      with their potential to grow. This study reports for the first time that the
      optic nerve has unique properties, which aids in the realization of these goals.

PMID- 11520117
TI  - Embryonic-derived glial-restricted precursor cells (GRP cells) can differentiate
      into astrocytes and oligodendrocytes in vivo.
AB  - We have isolated and characterized a unique glial-restricted precursor cell (GRP)
      from the embryonic spinal cord. Clonal analysis demonstrated that these cells are
      able to generate oligodendrocytes and two distinct type of astrocytes (type 1 and
      type 2) when exposed to appropriate signals in vitro. We now show that many
      aspects of these cells are retained in vivo. GRP cells are restricted to the
      glial lineage in vivo as they seem to be unable to generate neuronal phenotypes
      in an in vivo neurogenic environment. GRP cells survive and migrate in the
      neonatal and adult brain. Transplanted GRP cells differentiate into myelin
      forming oligodendrocytes in a myelin-deficient background and also generate
      immature oligodendrocytes in the normal neonatal brain. In addition, GRP cells
      also consistently generated glial fibrillary protein-expressing cells in the
      neonatal and adult brain, a property not consistently expressed by other glial
      precursor cells like the O-2A/OPC cells. We suggest that the lineage restriction
      of GRP cells and their ability to generate both oligodendrocytes and astrocytes
      in vivo together with their embryonic character that allows for extensive in
      vitro expansion of the population makes the cell useful for clinical application.

PMID- 11520118
TI  - Type II glucocorticoid receptors are involved in neuronal death and astrocyte
      activation induced by trimethyltin in the rat hippocampus.
AB  - According to our previous study, trimethyltin (TMT), a neurotoxicant, induces the
      loss of pyramidal neurons in the rat hippocampus, which is preceded by a
      transient increase in plasma corticosterone concentration. To address whether
      this transient activation of the hypothalamopituitary-adrenocortical axis is
      related to neuronal loss in the hippocampus, we evaluated the effects of
      bilateral adrenalectomy (ADX) and the chronic supplemental treatment of
      glucocorticoid receptor agonists after ADX on TMT-induced hippocampal damage.
      Peroral administration of a single dose of TMT (9 mg/kg body wt) induced the
      extensive loss of CA3 pyramidal neurons and reactive astrocytosis in the
      hippocampus, as evidenced by results of vimentin and glial fibrillary acidic
      protein immunohistochemistry, and the effects were profoundly exacerbated by
      bilateral adrenalectomy. Prolonged administration of corticosterone not only
      attenuated the exacerbating effects of adrenalectomy but also partially reversed
      the TMT-induced neuronal loss and reactive astrocytosis. Dexamethasone, but not
      aldosterone, could be substituted for corticosterone, suggesting a novel
      neuroprotective action of type II glucocorticoid receptors in the hippocampus.

PMID- 11520119
TI  - Involvement of microglial receptor for advanced glycation endproducts (RAGE) in
      Alzheimer's disease: identification of a cellular activation mechanism.
AB  - Receptor-mediated interactions with amyloid beta-peptide (Abeta) could be
      important in the evolution of the inflammatory processes and cellular dysfunction
      that are prominent in Alzheimer's disease (AD) pathology. One candidate receptor
      is the receptor for advanced glycation endproducts (RAGE), which can bind Abeta
      and transduce signals leading to cellular activation. Data are presented showing
      a potential mechanism for Abeta activation of microglia that could be mediated by
      RAGE and macrophage colony-stimulating factor (M-CSF). Using brain tissue from AD
      and nondemented (ND) individuals, RAGE expression was shown to be present on
      microglia and neurons of the hippocampus, entorhinal cortex, and superior frontal
      gyrus. The presence of increased numbers of RAGE-immunoreactive microglia in AD
      led us to further analyze RAGE-related properties of these cells cultured from AD
      and ND brains. Direct addition of Abeta(1-42) to the microglia increased their
      expression of M-CSF. This effect was significantly greater in microglia derived
      from AD brains compared to those from ND brains. Increased M-CSF secretion was
      also demonstrated using a cell culture model of plaques whereby microglia were
      cultured in wells containing focal deposits of immobilized Abeta(1-42). In each
      case, the Abeta stimulation of M-CSF secretion was significantly blocked by
      treatment of cultures with anti-RAGE F(ab')2. Treatment of microglia with anti
      RAGE F(ab')2 also inhibited the chemotactic response of microglia toward Abeta(1
      42). Finally, incubation of microglia with M-CSF and Abeta increased expression
      of RAGE mRNA. These microglia also expressed M-CSF receptor mRNA. These data
      suggest a positive feedback loop in which Abeta-RAGE-mediated microglial
      activation enhances expression of M-CSF and RAGE, possibly initiating an
      ascending spiral of cellular activation.

PMID- 11520120
TI  - Death of dopaminergic neurons in vitro and in nigral grafts: reevaluating the
      role of caspase activation.
AB  - Caspases are cysteine proteases involved in apoptotic cell death, and
      pharmacological caspase inhibition has been demonstrated to prevent neuronal cell
      death in certain experimental paradigms. In this study, the role of caspase-1 and
      -3 in the death of dopaminergic neurons derived from the E14 rat ventral
      mesencephalon (VM) has been examined in two model systems using peptide caspase
      inhibitors. First, cell death was induced in vitro by withdrawing serum after 2
      days. Different doses of caspase-1 (IL-1beta converting enzyme) and caspase-3
      inhibitors (Ac-DEVD-cmk) were added to the medium at the time of serum
      withdrawal, and the ability of the inhibitors to promote dopaminergic neuronal
      survival and prevent activation of caspase-3 was assessed at 7 days.
      Immunostaining using tyrosine hydroxylase (TH) and cleaved caspase-3 antibodies
      demonstrated that caspase-1 and -3 inhibitors reduce caspase-3 activation as well
      as overall cell death. This did not, however, improve the survival of TH-positive
      neurons, although it did appear to promote their maturation. The second paradigm
      investigated the effects of these inhibitors in the 6-hydroxydopamine rat model
      of PD, and similarly, addition of caspase-1 or -3 inhibitor during tissue
      preparation or immediately prior to grafting of VM tissue did not promote
      dopaminergic neuronal survival. These results demonstrate that the reduction of
      apoptotic cell death by pharmacological inhibition of caspase-1 and -3 does not
      increase dopaminergic neuronal survival in these paradigms and suggest either
      that caspase-3 activation is not the major determinant of dopaminergic neuronal
      death in vitro and in grafts or that the ability of caspase inhibitors to rescue
      cells depends upon the degree of apoptotic stress. This implies that strategies
      to improve dopaminergic cell survival in clinical programmes of transplantation
      for PD will need to target other pathways of cell death.

PMID- 11520121
TI  - Neurodegenerative changes associated with beta-amyloid deposition in the brains
      of mice carrying mutant amyloid precursor protein and mutant presenilin-1
      transgenes.
AB  - Mutations of amyloid precursor protein (APP) and presenilin-1 (PS1) lead to an
      increase in beta-amyloid (Abeta) production. Despite the fact that a number of
      transgenic mice develop cerebral Abeta plaques, few have been subjected to
      ultrastructural investigation and the sequence of events leading to Abeta plaque
      formation is unclear. We therefore investigated the doubly transgenic (mutant
      APP(K670N,M671L)-mutant PS1(M146L)) mouse, which develops Abeta deposits much
      earlier than singly transgenic littermates. Widespread Abeta plaques with or
      without a distinct core were found in gray matter. Abeta plaques were also
      present in white matter. Astrocytosis was greater around gray matter plaques than
      around white matter plaques. In some plaques, Abeta cores were associated with
      cell profiles containing prominent endoplasmic reticulum and a homogeneous
      cytoplasm that appeared to be neuronal. The morphology and location of other
      profiles indicated them to be microglia or oligodendrocytes. Some Abeta fibrils
      appeared to lie within these profiles, but they may have been simply surrounded
      by the cell profile since the profile membrane was not always visible. Dark
      atrophic neurons, whose morphology suggested that they were apoptotic, were
      present around gray matter plaques. Cerebrovascular Abeta deposition was also
      observed in the brains of APP/PS1 transgenic mice. Thus, the amyloid deposition
      and neuropathology observed in APP/PS1 mouse brain are similar to those in
      Alzheimer's disease and they appear to develop earlier and become more severe
      than in the other transgenic models currently available.

PMID- 11520122
TI  - In vivo extracellular recording of striatal neurons in the awake rat following
      unilateral 6-hydroxydopamine lesions.
AB  - The purpose of this study was to further understand the functional effects of
      dopaminergic input to the dorsal striatum and to compare the effects of
      dopaminergic lesions in awake and anesthetized animals. We examined the effects
      of unilateral 6-hydroxydopamine (6-OHDA) lesions of the ascending dopaminergic
      bundle on the firing properties of dorsal striatal neurons in the awake freely
      moving rat using chronically implanted microwire electrode arrays. We recorded
      extracellular activity of striatal neurons under baseline conditions and
      following the systemic injection of apomorphine in awake and anesthetized
      subjects. Firing rates were higher in the hemisphere ipsilateral to the 6-OHDA
      lesion compared to rates of neurons from the contralateral unlesioned hemisphere.
      Striatal firing rates from sham and no-surgery control rats were, in general,
      higher than those from the contralateral unlesioned striatum of experimental
      subjects. Apomorphine (0.05 mg/kg, sc) normalized the differences in firing rates
      in lesioned animals by increasing firing of neurons within the contralateral
      unlesioned side, while simultaneously decreasing firing of neurons within the
      ipsilateral lesioned side. Mean firing rates were substantially higher in awake
      animals than in subjects anesthetized with chloral hydrate, perhaps reflecting
      anesthesia-induced decreases in excitatory input to striatal neurons. Chloral
      hydrate anesthesia decreased firing rates of neurons in the lesioned, unlesioned,
      and control striata to a similar degree, although absolute firing rates of
      neurons from the 6-OHDA-lesioned striata remained elevated over all other groups.
      Unilateral 6-OHDA lesions also altered the pattern of spike output in the awake
      animal as indicated by an increase in the number of bursts per minute following
      dopaminergic deafferentation. This and other burst parameters were altered by
      apomorphine. Our findings show that effects of dopaminergic deafferentation can
      be measured in the awake behaving animal; this model should prove useful for
      testing the behavioral and functional effects of experimental manipulations
      designed to reduce or reverse the effects of dopaminergic cell loss. In addition,
      these results suggest that the contralateral changes in striatal function which
      occur in the unilateral dopaminergic lesion model should be considered when
      evaluating experimental results.

PMID- 11520123
TI  - Attenuation of staurosporine-induced apoptosis, oxidative stress, and
      mitochondrial dysfunction by synthetic superoxide dismutase and catalase
      mimetics, in cultured cortical neurons.
AB  - Neuronal apoptosis induced by staurosporine (STS) involves multiple cellular and
      molecular events, such as the production of reactive oxygen species (ROS). In
      this study, we tested the efficacy of two synthetic superoxide dismutase/catalase
      mimetics (EUK-134 and EUK-189) on neuronal apoptosis, oxidative stress, and
      mitochondrial dysfunction produced by STS in primary cortical neuronal cultures.
      Exposure of cultures to STS for 24 h increased lactate dehydrogenase (LDH)
      release, the number of apoptotic cells, and decreased trypan blue exclusion.
      Pretreatment with 20 microM EUK-134 or 0.5 microM EUK-189 significantly
      attenuated STS-induced neurotoxicity, as did pretreatment with the caspase-1
      inhibitor, Ac-YVAD-CHO, but not the caspase-3 inhibitor, Ac-DEVD-CHO.
      Posttreatment (1-3 h following STS exposure) with 20 microM EUK-134 or 0.5 microM
      EUK-189 significantly reduced STS-induced LDH release, in a time-dependent
      manner. Exposure of cultures to STS for 1 h produced an elevation of ROS, as
      determined by increased levels of 2,7-dichlorofluorescein (DCF). This rapid
      elevation of ROS was followed by an increase in lipid peroxidation, and both the
      increase in DCF fluorescence and in lipid peroxidation were significantly blocked
      by pretreatment with EUK-134. STS treatment for 3-6 h increased cytochrome c
      release from mitochondria into the cytosol, an effect also blocked by
      pretreatment with EUK-134. These results indicate that intracellular oxidative
      stress and mitochondrial dysfunction are critically involved in STS-induced
      neurotoxicity. However, there are additional cellular responses to STS, which are
      insensitive to treatment with radical scavengers that also contribute to its
      neurotoxicity.

PMID- 11520124
TI  - A clonal line of mesencephalic progenitor cells converted to dopamine neurons by
      hematopoietic cytokines: a source of cells for transplantation in Parkinson's
      disease.
AB  - Neural progenitor cells potentially provide a limitless, on-demand source of
      cells for grafting into patients with Parkinson's disease (PD) if the signals
      needed to control their conversion into dopamine (DA) neurons could be
      identified. We have recently shown that cytokines which instruct cell division
      and differentiation within the hematopoeitic system may provide similar functions
      in the central nervous system. We have shown that mitotic progenitor cells can be
      isolated from embryonic rat mesencephalon and that these cells respond to a
      combination of interleukin-1, interleukin-11, leukemia inhibitory factor, and
      glial cell line-derived neurotrophic factor yielding a tyrosine hydroxylase
      immunoreactive (THir) phenotype in 20-25% of total cells. In the present study,
      24 clonal cell lines derived from single cells of mesencephalic proliferation
      spheres were examined for their response to the cytokine mixture. The clone
      yielding the highest percentage of THir neurons (98%) was selected for further
      study. This clone expressed several phenotypic characteristics of DA neurons and
      expression of Nurr1. The response to cytokines was stable for several passages
      and after cryopreservation for several months. When grafted into the striatum of
      DA-depleted rats, these cells attenuated rotational asymmetry to the same extent
      as freshly harvested embryonic DA neurons. These data demonstrate that
      mesencephalic progenitor cells can be clonally expanded in culture and
      differentiated in the presence of hematopoietic cytokines to yield enriched
      populations of DA neurons. When transplanted, these cells provide significant
      functional benefit in the rat model of PD.

PMID- 11520125
TI  - Expression of neural markers in human umbilical cord blood.
AB  - A population of cells derived from human and rodent bone marrow has been shown by
      several groups of investigators to give rise to glia and neuron-like cells. Here
      we show that human umbilical cord blood cells treated with retinoic acid (RA) and
      nerve growth factor (NGF) exhibited a change in phenotype and expressed molecular
      markers usually associated with neurons and glia. Musashi-1 and beta-tubulin III,
      proteins found in early neuronal development, were expressed in the induced cord
      blood cells. Other molecules associated with neurons in the literature, such as
      glypican 4 and pleiotrophin mRNA, were detected using DNA microarray analysis and
      confirmed independently with reverse transcriptase polymerase chain reaction (RT
      PCR). Glial fibrillary acidic protein (GFAP) and its mRNA were also detected in
      both the induced and untreated cord blood cells. Umbilical cord blood appears to
      be more versatile than previously known and may have therapeutic potential for
      neuronal replacement or gene delivery in neurodegenerative diseases, trauma, and
      genetic disorders.

PMID- 11520126
TI  - Axotomy along with hypoxia enhances the neuronal NADPH-d/NOS expression in lower
      brain stem motor neurons of adult rats.
AB  - This study was aimed to determine whether axotomy coupled with hypoxia would
      exert a more profound effect on injury-induced neuronal nitric oxide synthase
      (NOS) expression. In this connection, the vagus and the hypoglossal nerves of
      adult rats were transected unilaterally in the same animal, and half of the
      operated animals were subjected to hypoxia treatment. Both the neuronal NOS
      immunohistochemistry and the nicotinamide adenine dinucleotide phosphate
      diaphorase (NADPH-d) histochemistry were used to assess the neuronal NOS
      expression. The present results have shown that the number of NADPH-d/NOS
      positive [NADPH-d/NOS(1)] neurons in the hypoglossal nucleus (HN) peaked at 14
      days after axotomy, while that in dorsal motor nucleus of vagus (DMN) and nucleus
      ambiguus (NA) was progressively increased up to 60 days. The up-regulation of
      NADPH-d/NOS in HN and DMN was more pronounced in hypoxic than in normoxic
      animals, a feature that was not evident in the NA. Quantitative analysis showed
      that the number of surviving motoneurons in normoxic animals was significantly
      higher than those subjected to hypoxia at 14 days postaxotomy in HN and at all
      postaxotomy time points in DMN. The difference may be attributed to their
      different functional components. Since O2 deprivation leads to poor cellular
      function, the stronger expression of NADPH-d/NOS and the more drastic neuronal
      loss following nerve transection in the hypoxic animals compared with the
      controls suggest that hypoxia plays an important role in peripheral neuropathies
      in which NO is implicated.

PMID- 11520127
TI  - L-dopa upregulates the expression and activities of methionine adenosyl
      transferase and catechol-O-methyltransferase.
AB  - High nonphysiological doses of l-dopa are administered to Parkinson's disease
      (PD) patients, to replenish the depleted dopamine (DA). A large portion of the
      administered L-dopa and the newly formed DA undergoes methylation by reacting
      with S-adenosyl-L-methionine (SAM). In the process SAM, as well as L-dopa and DA,
      is utilized and great demands are placed on the transmethylation system. In this
      study we investigated whether L-dopa increases the transmethylation process by
      inducing methionine adenosyl transferase (MAT), the enzyme that produces SAM, and
      catechol-O-methyl transferase (COMT), the enzyme that transfers the methyl group
      from SAM to L-dopa and DA. Swiss Webster mice were injected with L-dopa, four
      times/day, for 1 to 16 days. Brain DA, 3-O-methyldopa (3-OMD), SAM, S
      adenosylhomocysteine (SAH), MAT, and COMT were measured following a 24-h
      withdrawal period. An increase of 264% of brain DA occurred at days 2 and 3 after
      which it tapered to about 164% of control. The brain level of 3-OMD increased to
      870% of the control. SAM was increased by 44% after the sixth day and SAH level
      was about double after the second day. After day 3, MAT activity was increased by
      about 35%. Western blot analysis showed that MAT is more clearly characterized in
      10% mercaptoethanol reducing buffer in which 31.5-, 38- (beta), and 48-kDa
      (alpha1/alpha2) subunits were distinctly revealed. The induction of the 38-kDa
      and, more prominently, the 48-kDa subunits of MAT and the potential
      transactivator proteins of MAT, c-Jun/AP-1, was evident by day 6. The 31.5-kDa
      subunit was downregulated. COMT was detected as 24.7-, 30-, and 47.5-kDa bands in
      the brain, consistent with the membrane-bound COMT I (MB-COMT) and the dimeric
      COMT II. The 24.7- and the 30-kDa MB-COMT bands were induced in the brain by day
      6 and peaked on day 9. The highlight of the study is the fact that L-dopa induces
      the enzymes MAT and COMT. In addition, the downturn in brain DA after the sixth
      day coincides with the increase in SAM and the 48-kDa MAT protein. Thus, during
      PD treatment with L-dopa the induction of MAT and COMT is likely to occur and in
      turn increase the methylation and reduction of L-dopa and DA that may help cause
      the tolerance or the wearing-off effect developed to L-dopa.

PMID- 11520128
TI  - Mu- and delta-opioid receptor antagonists reduce levodopa-induced dyskinesia in
      the MPTP-lesioned primate model of Parkinson's disease.
AB  - Long-term treatment of Parkinson's disease with levodopa is complicated by the
      emergence of involuntary movements, known as levodopa-induced dyskinesia. It has
      been hypothesized that increased opioid transmission in striatal output pathways
      may be responsible for the generation of dyskinesia. In this study, we have
      investigated the effect of blockade of opioid peptide transmission on levodopa
      induced dyskinesia in a primate model of Parkinson's disease-the MPTP-lesioned
      marmoset. Coadministration of nonselective and mu- or delta-subtype-selective
      opioid receptor antagonists with levodopa resulted in a significant decrease in
      dyskinesia. There was no attenuation of the anti-parkinsonian actions of
      levodopa. These data suggest that specific mu- or delta-opioid receptor
      antagonists might be applicable clinically in the treatment of levodopa-induced
      dyskinesia in Parkinson's disease.

PMID- 11520129
TI  - Audiogenic seizure susceptibility is induced by termination of continuous
      infusion of gamma-aminobutyric acid or an N-methyl-D-aspartic acid Antagonist
      into the inferior colliculus.
AB  - The inferior colliculus (IC) is strongly implicated in seizure initiation in a
      genetic form of audiogenic seizures (AGS) and in AGS observed during ethanol
      withdrawal (ETX). Ethanol is known to block the actions of excitatory amino acids
      (EAA) and enhance the actions of gamma-aminobutyric acid (GABA) in several brain
      areas, including the IC. The present study investigated the effects on
      susceptibility to AGS following withdrawal from continuous blockade of N-methyl-D
      aspartic acid (NMDA) receptors or continuous activation of GABA receptors in the
      IC. This involved infusion of GABA (1 M) or a competitive NMDA antagonist, DL-2
      amino-7-phosphonoheptanoic acid (AP7, 1 mM), at 0.25 microl/h for 7 days using an
      Alzet osmotic minipump. Following abrupt termination of the infusion, AGS
      susceptibility began at 30 min. The incidence of AGS was 38.9 and 56.3% following
      GABA and AP7 withdrawal, respectively. The AGS behaviors observed during
      withdrawal, which included wild running and bouncing clonus, were very similar to
      those evoked by acoustic stimuli during ETX. AGS susceptibility lasted for
      several hours and in 13% of animals persisted for up to 6 months. The current
      results support diminished GABAergic and elevated glutamatergic function in the
      IC as the critical mechanisms and sites for AGS initiation. The present study,
      coupled with previous evidence that chronic ethanol exposure reduced GABA
      mediated inhibition and enhanced EAA-mediated excitation, suggests that these
      amino acid receptor-mediated alterations in the IC are key elements in initiating
      AGS during ethanol withdrawal.

PMID- 11520130
TI  - Degeneration and sprouting of identified descending supraspinal axons after
      contusive spinal cord injury in the rat.
AB  - Contusive spinal cord injury (SCI) results in the formation of a chronic lesion
      cavity surrounded by a rim of spared fibers. Tissue bridges containing axons
      extend from the spared rim into the cavity dividing it into chambers. Whether
      descending axons can grow into these trabeculae or whether fibers within the
      trabeculae are spared fibers remains unclear. The purposes of the present study
      were (1) to describe the initial axonal response to contusion injury in an
      identified axonal population, (2) to determine whether and when sprouts grow in
      the face of the expanding contusion cavity, and (3) in the long term, to see
      whether any of these sprouts might contribute to the axonal bundles that have
      been seen within the chronic contusion lesion cavity. The design of the
      experiment also allowed us to further characterize the development of the lesion
      cavity after injury. The corticospinal tract (CST) underwent extensive dieback
      after contusive SCI, with retraction bulbs present from 1 day to 8 months
      postinjury. CST sprouting occurred between 3 weeks and 3 months, with penetration
      of CST axons into the lesion matrix occurring over an even longer time course.
      Collateralization and penetration of reticulospinal fibers were observed at 3
      months and were more extensive at later time points. This suggests that these two
      descending systems show a delayed regenerative response and do extend axons into
      the lesion cavity and that the endogenous repair can continue for a very long
      time after SCI.

PMID- 11520131
TI  - Repeated injury to the sciatic nerve in immature rats causes motoneuron death and
      impairs muscle recovery.
AB  - Injury to the sciatic nerve of newborn rats causes motoneuron death, while the
      same insult inflicted 5 days later does not. In this study the effects of
      prolonging the period of target deprivation and axonal regeneration were
      investigated by inflicting a second nerve crush 6 days after the first, just
      before reinnervation of the muscle occurred. Two to 4 months later the number of
      motoneurons supplying soleus, tibialis anterior, and extensor digitorum longus
      muscles was established by retrograde labeling with horseradish peroxidase
      injected into the muscle. After nerve injury at 5 days there was no significant
      loss of motoneurons to any muscle. However, when the injury was repeated, the
      number of labeled motoneurons was reduced, suggesting that a significant
      proportion had died. Motoneurons to soleus were affected more than those to the
      fast muscles, reflecting their lesser maturity. Moreover, motoneurons to soleus
      that survived both injuries to their axon failed to grow to their full size. The
      relative impairment of recovery of the muscles, indicated by weight and maximal
      tetanic tension, mirrored the loss of motoneurons in each case. Previous studies
      have suggested that repeated nerve injuries in adult animals can enhance
      reinnervation. However, the present results along with those of other recent
      studies suggest that immature motoneurons that are repeatedly induced to support
      growth of their axons are at greater risk of death and can result in poorer
      reinnervation of the muscles.

PMID- 11520132
TI  - Activation of a latent respiratory motor pathway by stimulation of neurons in the
      medullary chemoreceptor area of the rat.
AB  - Previous studies have demonstrated that during respiratory stress (hypercapnia
      and hypoxia), a latent crossed respiratory pathway can be activated to produce
      hemidiaphragm recovery following an ipsilateral C2 spinal cord hemisection. The
      present study investigates the effects of ventral medullary chemoreceptor area
      stimulation by microinjection of (1S,3R)-aminocyclopentanedicarboxylic acid
      (ACPD), a glutamate metabotropic receptor agonist, on activating the latent
      pathway following left C2 spinal cord hemisection in rats in which end-tidal CO2
      was maintained at a constant level. Experiments were conducted on anesthetized,
      vagotomized, paralyzed, and artificially ventilated rats in which phrenic nerve
      activity was recorded bilaterally. Before drug injection, the phrenic nerve
      contralateral to hemisection showed vigorous respiratory-related activity, but
      the phrenic nerve ipsilateral to hemisection showed no discernible respiratory
      related activity. ACPD (1-100 nl, 1 mM) was injected directly into the region of
      the retrotrapezoid nucleus (RTN), a known medullary chemoreceptor area.
      Microinjection of ACPD into the right RTN increased respiratory-related activity
      in the right phrenic nerve (contralateral to hemisection). ACPD (>5 nl, 1 mM)
      microinjection also significantly induced respiratory recovery in the phrenic
      nerve ipsilateral to hemisection in a dose-dependent manner. The present study
      indicates that respiratory recovery can be achieved by stimulation of respiratory
      circuitry without increasing CO2 levels.

PMID- 11520133
TI  - Placental site trophoblastic tumor--past as prologue.

PMID- 11520134
TI  - Placental site trophoblastic tumor: a 17-year experience at the New England
      Trophoblastic Disease Center.
AB  - OBJECTIVE: We reviewed cases of placental site trophoblastic tumors from the New
      England Trophoblastic Disease Center (NETDC) database from 1982-1999 in an effort
      to identify prognostic factors for recurrent disease. METHODS: A chart review was
      performed utilizing patients identified from the NETDC database. Data obtained
      included patient age at diagnosis, antecedent pregnancy, duration and extent of
      disease, presenting symptoms, pre- and posttreatment hCG levels, diagnostic and
      therapeutic procedures, treatment and outcome of patients. Statistical analysis
      was performed using Student's t test and chi(2) test when appropriate. RESULTS:
      Thirteen patients were identified. All ultimately underwent hysterectomy although
      initial treatment of 1 patient was uterine resection. There were 5 recurrences
      (43%)--3 among the 9 patients who had no metastases on presentation (33%) and 2
      of 3 patients who presented with metastases (66%). The 5 patients who recurred
      were among 8 who had received peri- or postoperative chemotherapy (62.5%).
      Treatment of recurrences included continued or alternate chemotherapy,
      radiotherapy, and/or excision of locally recurrent disease. Follow up time
      averaged 56.2 months (range 12-182 months). One of the 4 patients receiving
      chemotherapy < or =1 week after hysterectomy recurred, whereas all 4 patients who
      received chemotherapy 3 weeks or more after hysterectomy recurred. Uterine tumor
      volume was significantly greater, 154.1 cm(3), in patients with initial
      metastases versus 42.3 cm(3) in patients without initial metastases (P = 0.04).
      Mitotic index (P = 0.04) was significantly increased in patients who developed
      recurrent disease. CONCLUSION: High mitotic index appears to be an adverse
      prognostic indicator for recurrence. Hysterectomy remains the mainstay of
      treatment. Chemotherapy is indicated for patients with metastases and may be
      indicated when the mitotic index is >5 mitoses/10 HPF. Radiation treatment may
      play a role in recurrent disease but must be evaluated on a case-by-case basis.

PMID- 11520135
TI  - High-dose topotecan, melphalan, and cyclophosphamide (TMC) with stem cell
      support: a new regimen for the treatment of advanced ovarian cancer.
AB  - OBJECTIVE: The goal of this study was to determine the optimal dose of topotecan
      when used in combination with high-dose melphalan and cyclophosphamide (TMC), and
      to assess the toxicity and efficacy of the regimen in patients with advanced
      ovarian cancer. METHODS: Fifty-three patients with persistent or recurrent
      ovarian cancer were treated. Disease status at study entry included: platinum
      sensitive recurrent disease (15 patients), platinum-resistant or refractory
      recurrent disease (15 patients), positive second-look surgery (16 patients),
      failure to achieve a primary clinical complete response (CR) (7 patients).
      Following stem cell mobilization and collection, patients were given
      cyclophosphamide 1 g/m(2)/day on Days -6, -5, -4; melphalan 70 mg/m(2)/day on
      Days -3, -2; and topotecan at escalating doses from 1.25 to 4.0 mg/m(2)/day on
      Days -6 to -2. Peripheral blood stem cells were infused on Day 0. RESULTS: The
      optimal topotecan dose selected for future trials was 4.0 mg/m(2)/day x 5 days.
      The regimen had acceptable toxicity with no regimen-related death. Toxicity
      (Bearman toxicity criteria) was limited mostly to grade 1-2 mucositis and
      diarrhea. The overall response rate of patients with measurable or evaluable
      disease was 93%. Median survival has not yet been reached, but with a median
      follow up of 18 months (range: 11-37) 77% of patients are alive. CONCLUSION: With
      a topotecan dose of 4.0 mg/m(2)/day x 5 days, the TMC regimen has acceptable
      toxicity and produces high response rates. In the setting of ovarian cancer, high
      dose chemotherapy should be administered only as part of well-designed clinical
      trials. TMC should be considered a potential regimen for future randomized trials
      in patients with advanced ovarian cancer.

PMID- 11520136
TI  - Steroid sulfatase expression in ovarian clear cell adenocarcinoma:
      immunohistochemical study.
AB  - OBJECTIVE: Steroid sulfatase (STS) is an important enzyme that converts
      biological inactive steroid sulfate to active free steroid. As estrogen is
      thought to play an important role in cell proliferation in gynecological cancer,
      the existence of STS may have particular significance in the prognosis of ovarian
      cancer. In the present study, we determined the STS expression of ovarian clear
      cell adenocarcinoma (OCCA), which has the poorest prognosis among various ovarian
      cancers, immunohistochemically to clarify the biological nature of OCCA and also
      to determine whether STS expression is one of the prognostic factors in OCCA.
      METHODS: Forty-five archival, formalin-fixed, paraffin-embedded tissues from
      patients with OCCA and other epithelial ovarian cancers who were first operated
      on from 1987 to 1998 were subjected to analysis. Twenty-eight of forty-five
      (60.9%) OCCA cases coexisted with endometriosis. They were subclassified into
      papillary, solid, and tubulocystic types with respect to architectural pattern.
      Immunohistochemical staining of STS was performed using anti-human STS polyclonal
      rabbit antibody that had been immunized with purified STS from human placenta.
      RESULTS: STS was immunohistochemically stained positively in 70% (32/45) of OCCA,
      33.3% of serous adenocarcinoma (6/18), and 50.0% of mucinous adenocarcinoma (4/8)
      specimens and was localized in the cytoplasm of neoplastic epithelial cells. No
      significant relationship was found between STS staining and FIGO staging.
      However, patients diagnosed as papillary type had a significantly lower survival
      rate and showed significantly more positive staining of STS (P < 0.05) than those
      with solid type. Stage, STS expression, and architectural type yielded a
      significant association with survival rate. CONCLUSION: It was proven that STS is
      present in the cytoplasm of patients with OCCA by an immunohistochemical method.
      OCCA patients with papillary tumor with positive STS expression are considered to
      have a poor prognosis.

PMID- 11520137
TI  - Procedures required to accomplish complete cytoreduction of ovarian cancer: is
      there a correlation with "biological aggressiveness" and survival?
AB  - OBJECTIVE: The aim of this study was to determine if the necessity of using
      specific procedures to attain complete cytoreduction in ovarian cancer correlates
      with innate biologic aggressiveness and independently influences survival.
      METHODS: Between 1990 and 2000, 213 patients with Stage IIIC epithelial ovarian
      cancer underwent complete cytoreduction before initiation of systemic platinum
      based combination chemotherapy. Survival was stratified and analyzed (log rank
      and Cox regression) on the basis of whether extrapelvic bowel resection,
      diaphragm stripping, full-thickness diaphragm resection, modified posterior
      pelvic exenteration, peritoneal implant ablation and/or aspiration, and excision
      of grossly involved retroperitoneal lymph nodes were necessary to attain a
      visibly disease-free cytoreductive outcome. RESULTS: The median and estimated 5
      year survival for the cohort were 75.8 months and 54%, respectively. Survival was
      influenced (log rank) by the requirement of diaphragm stripping (required, median
      42 months vs not required, median 79 months; P = 0.03) and the extent of
      mesenteric and serosal implants that required removal (none, median not reached,
      vs 1-50 implants, median not reached, vs >50 implants, median 40 months; P =
      0.002). Survival was independently influenced (Cox regression) only by the extent
      of peritoneal metastatic implants that required removal (P = 0.01). The other
      investigated procedures and type of chemotherapy used did not influence survival.
      CONCLUSIONS: The need to remove a large number of peritoneal implants correlates
      with biological aggressiveness and diminished survival, but not significantly
      enough to preclude long-term survival or justify abbreviation of the operative
      effort. The need to use the other investigated procedures had minimal or no
      observed influence on survival.

PMID- 11520139
TI  - Cytoplasmic/nuclear expression without mutation of exon 3 of the beta-catenin
      gene is frequent in the development of the neoplasm of the uterine cervix.
AB  - OBJECTIVE: The dual function of beta-catenin (e.g., as an intermediate protein
      between adherence junctions and the microfilaments, and as a mediator of the Wnt
      signaling pathway) is currently known. Stabilization of beta-catenin and
      subsequent activation of the Wnt signaling pathway are involved in the
      development of some malignancies. We analyzed the immunohistochemical
      localization of beta-catenin and the somatic mutation of exon 3 of the beta
      catenin gene in the malignant phenotype of the uterine cervix. METHODS:
      Immunohistochemical localization of beta-catenin and mutation of exon 3 of the
      beta-catenin gene were analyzed in 38 precancerous lesions and 43 cancerous
      lesions. RESULTS: In normal cervix, beta-catenin was observed around the plasma
      membrane of the cells in the basal and parabasal layers of the epithelium. The
      frequency of cytoplasmic/nuclear beta-catenin expression correlated with a high
      histological grade of cervical intraepithelial neoplasia. Among invasive
      carcinomas, 11 (73%) of 15 samples showed cytoplasmic/nuclear localization to
      variable extents. A mutational analysis showed that mutation occurred in 7 of 68
      specimens. Six cases with mutations revealed cytoplasmic/nuclear beta-catenin
      expression, though 32 (84%) of the 38 samples showing cytoplasmic/nuclear beta
      catenin expression were not associated with the mutation. CONCLUSION: These
      results indicate that cytoplasmic/nuclear expression of beta-catenin is
      associated with the malignant phenotype of the cervix, but the contribution of
      mutation of the beta-catenin gene is limited.

PMID- 11520138
TI  - Localization of matrix metalloproteinases on endometrial cancer cell invasion in
      vitro.
AB  - OBJECTIVES: In this study, we have established an in vitro three-dimensional (3D)
      coculture, where normal endometrial stromal cells and endometrial cancer cells
      were cocultured under defined hormonal conditions, to investigate the potential
      paracrine effects on synthesis and secretion of matrix metalloproteinases (MMPs)
      and, thus, cancer invasion. METHODS: Endometrial stromal cells were obtained by
      biopsy, cultured in the presence of 100 nM estrogen for 3 days, and then mixed
      with extracellular matrix (ECM) composed of collagen I and matrigel in a 4:1
      ratio. After 3 more days in culture, a 3D coculture was established with HEC-1A
      cells, an endometrial adenocarcinoma cell line, grown on top of the mixture under
      various ovarian steroids (no steroid, 100 nM beta-estradiol (E2), or 1.0 microM
      progesterone (P4)) for 10 days. The expression and localization of MMP-2, MMP-9,
      and integrin beta 3 subunit were visualized by immunocytochemistry and analyzed
      by reverse transcription polymerase chain reaction (RT-PCR). The extent of cancer
      invasion was quantified by Boyden's chamber assay. RESULTS: Integrin beta 3
      subunit was localized along the cell surface of HEC-1A cell under all three
      hormonal conditions. MMP-2 was located in the cytoplasm of stromal cells and on
      the surface of HEC-1A cells. Synthesis and secretion of stromal MMP-2 were
      increased in the presence of ovarian steroids. In contrast, expression of stromal
      MMP-9 was suppressed in the presence of ovarian steroids. No MMPs were
      synthesized in HEC-1A cells. Invasion assay revealed that HEC-1A cells achieved
      high tumoral invasiveness in the presence of beta-estradiol. CONCLUSIONS: These
      findings suggest that stromal cell-derived MMP-2 is translocated to the surface
      of HEC-1A cells. Integrin beta 3 subunit might contribute, in part, to providing
      a binding site for MMP-2. Thus, HEC-1A cells invade by recruiting MMP-2 secreted
      by stromal cells, which is greatly enhanced in the presence of beta-estradiol.
      The 3D coculture provides an excellent experimental system in which single
      parameters can be isolated from a complex in vivo system in the process of
      endometrial cancer invasion.

PMID- 11520140
TI  - Initial clinical experience with intensity-modulated whole-pelvis radiation
      therapy in women with gynecologic malignancies.
AB  - OBJECTIVE: Our goal in this article to describe our initial experience with
      intensity-modulated whole-pelvis radiation therapy (IM-WPRT) in gynecologic
      malignancies. METHODS: Between February and August 2000, 15 women with cervical
      (9) or endometrial (6) cancer received IM-WPRT. All patients received a treatment
      planning computed tomography (CT) scan. On each scan, the target volume (upper
      vagina, parametrial tissues, presacral region, uterus, and regional lymph nodes)
      and normal tissues (small bowel, bladder, and rectum) were identified. Using
      commercially available software, an IM-WPRT plan was generated for each patient.
      The goal was to provide coverage of the target with the prescription dose (45 Gy)
      while minimizing the volume of small bowel, bladder, and rectum irradiated. Acute
      gastrointestinal (GI) and genitourinary (GU) toxic effects in these women were
      compared with those seen in 25 patients treated with conventional WPRT. RESULTS:
      IM-WPRT plans provided excellent coverage of the target structures in all
      patients and were highly conformal, providing considerable sparing of the
      bladder, rectum, and small bowel. Treatment was well tolerated, with grade 0-1 GI
      and GU toxicity in 46 and 93% of patients, respectively. IM-WPRT patients had a
      lower rate of grade 2 GI toxicity (53.4% vs 96%, P = 0.001) than those treated
      with conventional WPRT. Moreover, the percentage of women requiring no or only
      infrequent antidiarrheal medications was lower in the IM-WPRT group (73.3% vs
      20%, P = 0.001). While grade 2 GU toxicity was also lower in the IM-WPRT patients
      (6.7% vs 16%), this difference did not reach statistical significance (P = 0.38).
      CONCLUSION: IM-WPRT provides excellent coverage of the target structures while
      sparing critical neighboring structures in gynecology patients. Treatment is well
      tolerated with less acute GI toxicity than conventional WPRT. More patients and
      longer follow-up are needed to evaluate the full merits of this approach.

PMID- 11520141
TI  - The costs and efficacy of liposomal doxorubicin in platinum-refractory ovarian
      cancer in heavily pretreated patients.
AB  - OBJECTIVE: In clinical practice, chemotherapy agents demonstrating modest second
      line activity against platinum-refractory epithelial ovarian cancer (PROC) are
      frequently used in patients who have received multiple prior chemotherapy agents.
      Whether the response rates reported in selected patients can be expected in
      heavily pretreated patients is not known. Similarly, the costs of palliative
      chemotherapy are not known. We sought to determine the response, survival, and
      predictors of response in an unselected cohort of PROC patients receiving
      liposomal doxorubicin (LD) for relapsed disease, and the overall costs of
      delivering liposomal doxorubicin in this setting. METHODS: In a cohort of 62
      consecutive patients who initiated LD as second- or greater-line therapy for
      PROC, the following variables were examined: age, number of prior regimens for
      relapse disease, duration of first clinical remission, time from last prior
      treatment, dose intensity of LD received, response/clinical benefit, time to
      progression, toxic effects, and survival. Multivariate analyses were used to
      identify predictors of clinical benefit and overall survival. Direct medical
      charges were calculated and converted to costs, and major cost drivers
      determined. RESULTS: Sixty-two patients received a total of 174 cycles of LD. The
      mean number of cycles per patient was 2 (range, 1-8); the median number of prior
      regimens for recurrent PROC was 2 (range, 0-8); and the median duration of the
      first clinical remission was 6 months. Median dose intensity of LD delivered was
      11.4 mg/m(2)/week (range, 2.8-16.7 mg/m(2)/week). Nine of sixty-two patients
      (14.5%) had an objective clinical response by CA-125 and/or CT scan (95%
      confidence interval, 6-23%). Grade 3/4 toxicity occurred in 11% of patients. In
      the full cohort, median time to progression was 2.2 months, and median overall
      survival, 9.6 months (range, 0.2-26 months). Dose intensity was the only
      independent predictor of overall response. Duration of first clinical remission
      and number of prior salvage regimens were associated with longer overall
      survival. The mean total direct medical cost per cycle of LD was $5763, and the
      major cost drivers were hospitalizations and drug acquisition/delivery costs.
      CONCLUSION: LD is an active agent in PROC, even when used as greater-than-second
      line therapy. Among heavily pretreated patients, delivering a dose intensity of
      at least 9.0 mg/m(2)/week was associated with a higher probability of response.
      The cost per cycle of LD is driven by hospitalizations and drug
      acquisition/delivery costs.

PMID- 11520142
TI  - Positive peritoneal cytology in endometrial cancer: enhancement of other
      prognostic indicators.
AB  - OBJECTIVE: The goal of this study was to investigate the prognostic significance
      of positive peritoneal cytology in endometrial cancer. METHODS: A
      clinicocytopathological study was performed in 534 patients with endometrial
      cancer to assess the prognostic value of positive peritoneal cytology. The study
      population was divided into three groups: a low-risk group (disease limited to
      the uterus, grade 1, and depth of invasion < or =1/2), a moderate-risk group
      (disease limited to the uterus, grade 2 or 3, and/or depth of invasion >1/2), and
      a high-risk group (extrauterine disease). In each group, disease-free survival
      was compared in the patients who were positive or negative for malignant cells.
      RESULTS: The overall incidence of positive peritoneal cytology was 22.3%
      (119/534). The 5-year disease-free survival of patients positive or negative for
      malignant cells was 98.1% versus 100% in the low-risk group (n = 250), 77.5%
      versus 91.3% in the moderate-risk group (n = 211), and 42.9% versus 72.1% in the
      high-risk group (n = 73). A significant difference was noted in the moderate-risk
      (P = 0.044) and high-risk (P = 0.015) groups, but not in the low-risk group (P =
      0.56). CONCLUSIONS: Positive peritoneal cytology is not a negative prognostic
      indicator itself, but it potentiates other prognostic indicators for endometrial
      cancer. Our findings also suggest that patients with positive peritoneal cytology
      in the absence of other adverse prognostic factors do not need upstaging.

PMID- 11520143
TI  - Tumor diameter and volume assessed by magnetic resonance imaging in the
      prediction of outcome for invasive cervical cancer.
AB  - OBJECTIVE: The aim of this study was to evaluate the predictive value of
      pretherapeutic magnetic resonance imaging (MRI)-based measurements of tumor
      diameter and volume with regard to recurrent disease. METHODS: MRI on 0.5- or 1.5
      T scanners was performed in 126 consecutive women with invasive carcinoma of the
      uterine cervix. Initial tumor diameter and volume were determined on T(2)
      weighted images; volume was calculated by the standard technique of multiplying
      the sum of the areas by the slice thickness. Patients were treated by radical
      surgery, radiotherapy, or a combined approach based on clinical International
      Federation of Gynecology and Obstetrics (FIGO) stage and individual patient
      criteria. Clinical data (patient age and FIGO stage), MRI-derived tumor
      dimensions (diameter and volume), and histological findings (tumor invasion depth
      and lymph-node involvement) were associated and linked to patient outcome.
      RESULTS: MRI-based tumor diameter correlated strongly with histological tumor
      invasion depth and lymph-node status (P < 0.01 and P = 0.01) while tumor volume
      on MRI was significantly associated only with tumor invasion depth into adjacent
      tissues (P < 0.01). Univariate analysis demonstrated graphically that MRI-derived
      tumor diameter and volume and clinical FIGO stage are associated with progression
      free survival. Correlation analysis showed a strong association between MRI
      derived tumor diameter and volume on MRI (r = 68%, P < 0.01) and also
      demonstrated a correlation between tumor diameter on MRI and FIGO stage Ib (Ib1
      versus Ib2) cervical tumors (r = 46.7%, P < 0.01). CONCLUSION: Tumor diameter and
      volume, determined by pretreatment MRI examinations, predict progression-free
      survival for patients with invasive cervical carcinoma. This study demonstrates
      the value of MRI as an adjunct to clinical evaluation of invasive cervical
      cancer, providing more complete assessment of morphological risk factors
      important in patient prognosis and treatment planning.

PMID- 11520145
TI  - What are the current surgical objectives, strategies, and technical capabilities
      of gynecologic oncologists treating advanced epithelial ovarian cancer?
AB  - OBJECTIVE: The purpose of this survey was to determine the range of surgical
      objectives, strategies, and outcomes of primary cytoreductive operations
      performed by gynecologic oncologists. METHODS: A survey addressing the definition
      of "optimal" cytoreduction, the use of neoadjuvant chemotherapy, disease sites
      precluding optimal cytoreduction, reasons optimal cytoreduction or cytoreduction
      to a visibly disease-free outcome is or is not accomplished, the use of 15
      specific operative procedures, and attitude toward postfellowship training in the
      surgical management of advanced stage epithelial ovarian cancer was mailed to
      candidate and full members of the Society of Gynecologic Oncologists. Analysis of
      discrete and binomial data utilized the chi(2) and independent samples t tests.
      Logistic regression confirmed relationships between responses and both the
      definition of optimal cytoreduction and the attitudes toward postfellowship
      training. RESULTS: Three hundred ninety-three (61.4%) of 640 physicians provided
      utilizable data. A median of 95% of patients were reported to be operated on
      primarily and 5% were treated with neoadjuvant chemotherapy (P < 0.0001). A
      median of 9 (range 0-15) of the surveyed procedures were utilized. Forty-seven
      (12.0%) respondents defined optimal cytoreduction as no residual disease, 54
      (13.7%) used a 5-mm threshold, 239 (60.8%) used a 1-cm threshold, and 48 (12.6%)
      utilized a 1.5- to 2.0-cm threshold. Small dimensions of residual disease (0-5 mm
      versus 1-2 cm) defined optimal cytoreduction for physicians indicating that fewer
      disease sites precluded optimal cytoreduction (P = 0.02), using a larger number
      of the surveyed procedures (P = 0.04), and in practice longer (P = 0.001). Three
      hundred seventeen (83.9%) of 378 respondents favored development of
      postfellowship training in cytoreductive surgery. Physicians against
      postfellowship training used fewer of the surveyed procedures because of concerns
      about efficacy (P = 0.01). More recent fellowship graduates favored
      postfellowship training (P = 0.01). CONCLUSIONS: A range of surgical objectives,
      strategies, procedures used, and outcomes exists among gynecologic oncologists.
      Confirmation of the efficacy of cytoreductive surgery may cultivate a consensus
      about the most appropriate therapeutic objective and strategy for advanced
      ovarian cancer. Cooperative efforts should be undertaken to offer postfellowship
      training.

PMID- 11520144
TI  - A comparison of epithelial membrane antigen overexpression in benign and
      malignant endometrium.
AB  - OBJECTIVE: The aim of this study was to analyze the value of epithelial membrane
      antigen (EMA) overexpression in benign and malignant endometrium and its
      prognostic significance. METHODS: EMA immunostaining was performed in 178
      paraffin-embedded specimens including 105 endometrial cancers, 40 endometrial
      hyperplasias, and 33 benign endometriums. EMA immunostaining was correlated with
      traditional prognostic factors and progression-free survival in endometrial
      cancer specimens. RESULTS: EMA overexpression was observed more frequently in
      adenocarcinomas (60%) than in hyperplasias (15%) or benign endometrium (9.1%).
      EMA overexpression was observed in two patients with endometrial hyperplasia who
      progressed to carcinoma. In adenocarcinomas, EMA overexpression had a positive
      correlation with nonendometrioid subtypes (P = 0.012). In multivariate analysis,
      FIGO stage (P = 0.025) and EMA overexpression (P = 0.017) were independent
      prognostic factors for progression-free survival. CONCLUSIONS: EMA overexpression
      appears to be a marker of malignant transformation in the endometrium and it is
      an independent predictor of recurrent disease in endometrial cancer.

PMID- 11520146
TI  - Laparoscopic pelvic and paraaortic lymph node dissection: analysis of the first
      100 cases.
AB  - OBJECTIVE: The aim of this study was to analyze the first 100 cases of planned
      laparoscopic pelvic and paraaortic lymph node dissection (LND) done for staging
      of gynecologic cancers. The goal of the study was to assess prognostic factors
      for conversion to laparotomy and document complications. METHODS: A retrospective
      review of patients who had planned laparoscopic bilateral pelvic and bilateral
      paraaortic LND for staging of their gynecologic cancer was performed. Patients
      were identified by our institutional database and data were collected by review
      of their medical records. Data were obtained regarding demographics, stage,
      histology, length of stay, and procedural information including completion rates,
      operating room time, estimated blood loss, assistant, lymph node count, and
      complications. Associations between variables were analyzed using Student t
      tests, analysis of variance, and chi(2) testing (Excel v7.0). RESULTS: A total of
      103 patients were identified from 12/15/95 to 8/28/00. Demographics included mean
      age of 66.2 (25-92) and mean Quetelet index (QI) of 30.8 (15.9-56.1). A total of
      34/103 (33.0%) had > or =1 previous laparotomy. Ninety-five patients had
      endometrial cancer and 8 had ovarian cancer. Eighty-six of 103 (83.5%) were stage
      I or II. The length of stay was shorter for those who had laparoscopy than for
      those who needed conversion to laparotomy (2.8 vs 5.6 days, P < 0.0001).
      Laparoscopy was completed in 73/103 (70.9%) of the cases. Completion rates were
      62/76 (81.6%) with QI < 35 vs 11/27 (40.7%) with QI > or = 35, P < 0.001.
      Significantly more patients had their laparoscopy completed when an attending
      gynecologic oncologist was the first assistant compared to a fellow or a
      community obstetrician/gynecologist (92.9%, 69.0%, 64.5%, P < 0.0001). The top
      three reasons for conversion to laparotomy were obesity, 12/30 (29.1%),
      adhesions, 5/30 (16.7%), and intraperitoneal disease, 5/30 (16.7%). Pelvic,
      common iliac, and paraaortic lymph node counts did not differ when compared to
      those of patients who had conversion to laparotomy (18.1, 5.1, 6.8 vs 17.3, 5.7,
      6.8, P = ns). Complications included 2 urinary tract injuries, 2 pulmonary
      embolisms, and 6 wound infections (all in the laparotomy group). Two deaths
      occurred, 1 due to a vascular injury on initial trocar insertion and 1 due to a
      pulmonary embolism after a laparotomy for bowel herniation through a trocar
      incision. CONCLUSION: Laparoscopic bilateral pelvic and paraaortic LND can be
      completed successfully in 70.9% of patients. Age, obesity, previous surgery, and
      the need to perform this procedure in the community were not contraindications.
      Advantages include a shorter hospital stay, similar nodal counts, and acceptable
      complications.

PMID- 11520147
TI  - A comparison of ovarian metastasis between squamous cell carcinoma and
      adenocarcinoma of the uterine cervix.
AB  - OBJECTIVE: The purpose of our study was to investigate a possible difference in
      ovarian metastasis between squamous cell carcinoma and adenocarcinoma of the
      uterine cervix and to confirm clinicopathological variables associated with the
      metastases. METHODS: Clinical and pathological variables of 1064 patients with
      invasive squamous cell carcinoma and 240 with adenocarcinoma were studied.
      RESULTS: Ovarian metastasis was found in 14 patients (1.3%) with squamous cell
      carcinoma and 15 (6.3%) with adenocarcinoma. The mean age of patients with
      ovarian metastasis of squamous cell carcinoma was 57.4 years, compared to 50.2
      years for adenocarcinoma. Ovarian metastasis of adenocarcinoma was more likely to
      be visible (40.0%) and present in both ovaries (66.7%), while these two
      characteristics occurred in only 21.4 and 36.7% of patients with squamous cell
      carcinoma. A logistic regression analysis with clinical variables indicated that
      clinical stage beyond IIb was a significant variable of squamous cell carcinoma,
      and more than 30-mm tumor size was significant in adenocarcinoma. CONCLUSION: The
      incidence of ovarian metastasis of adenocarcinoma of the uterine cervix was
      significantly higher than that of squamous cell carcinoma. The incidence of
      adenocarcinoma was associated more closely with tumor size than clinical stage,
      whereas it was more associated with clinical stage in squamous cell carcinoma.
      The results thus suggested that the differences in ovarian metastases were caused
      by the different characteristics of the two types of carcinoma.

PMID- 11520148
TI  - Choices in creating continent urostomies following pelvic exenteration for
      gynecologic malignancies.
AB  - OBJECTIVE: The purpose of this report was to describe a rationale for choosing
      from a variety of techniques to construct continent urinary diversions for
      patients who undergo pelvic exenterations. Moreover, this report evaluated the
      technique and utility of a continent urostomy created from a supracecal segment
      of colon. METHODS: The charts from patients who underwent pelvic exenterations
      and urinary diversions by DFS between September 1999 and December 2000 were
      reviewed after institutional review board approval. Data were recorded and
      evaluated. RESULTS: Four patients underwent total pelvic exenterations and one
      received an anterior exenteration. Recurrent vulvar, vaginal, and cervical
      cancers were diagnosed in one, one, and two of the patients. One patient had an
      unknown primary squamous cell carcinoma in the pelvis. Four of the five received
      prior pelvic radiotherapy either in the neoadjuvant setting or as treatment for
      their primary disease. All five patients chose to have continent urostomies
      constructed. One Kock (ileal) pouch, one Miami (iliocolonic) pouch, and three
      supracecal colonic continent urostomies (SCCCU) were built. All five maintained
      continence over the follow-up period (mean follow-up time = 8.2 months). No
      complications related to the urostomies required reoperation. A new technique to
      for the construction of a SCCCU is described. CONCLUSION: With a variety of
      procedures established to build continent urostomies, the choice of which to use
      should be individualized to the patient's situation as well as to the surgeon's
      experience. The use of a SCCCU requires moderately complex manipulations of the
      colon (described in the text) and a slight increase in the operative time;
      however, it results in successful continence and avoids complications related to
      radiation-injured bowel. It may be considered the procedure of choice for
      patients who have received prior radiation therapy. Long-term follow-up is
      needed.

PMID- 11520149
TI  - Biopsy correlates of abnormal cervical cytology classified using the Bethesda
      system.
AB  - OBJECTIVE: The goal of this study was to determine the colposcopic findings
      underlying cytologic abnormalities classified according to the Bethesda system.
      METHODS: Women undergoing colposcopy for abnormal cytology at an urban teaching
      hospital between July 1, 1996 and December 31, 1999 had Papanicolaou smears
      repeated. Results were compared both with biopsy histology and with the worst
      histology reported after 8-26 months of follow-up. kappa statistics and
      Spearman's rho were calculated to determine the degree of agreement. RESULTS:
      Colposcopy was performed for 2263 (94%) women. Referral and repeat Pap smears
      were reported identically in 493 (25%) of the 1962 women with results for both.
      No AGUS (atypical glandular cells of uncertain significance) smears were
      confirmed on repeat smear, and after excluding AGUS, agreement within one grade
      was found in 1305 of 1854 (70%). Among the 1842 women with squamous cytologic
      abnormalities, biopsy revealed a lesion more severe than that suggested by
      referral cytology in 577 (31%) and a less severe lesion in 648 (35%); exact
      correspondence was found in only 646 (35%). Of 317 women with ASCUS (atypical
      squamous cells of uncertain significance) on referral Pap smear, a negative
      repeat smear, and a specific biopsy result, 95 (30%) had true negative histology,
      while 148 (47%) had condyloma, 56 (18%) had cervical intraepithelial neoplasia
      (CIN) 1, 8 (3%) had CIN 2, 10 (3%) had CIN 3, and none had cancer. Comparison of
      repeat smear and colposcopic biopsy yielded a kappa statistic of 0.16.
      CONCLUSIONS: Cytology classified according to the Bethesda system does not
      accurately predict histologic diagnosis.

PMID- 11520150
TI  - Soluble urokinase plasminogen activator receptor in preoperatively obtained
      plasma from patients with gynecological cancer or benign gynecological diseases.
AB  - OBJECTIVE: The present study was planned to measure preoperative levels of
      soluble urokinase plasminogen activator receptor (suPAR) in plasma from patients
      with gynecological diseases, and to test for a relationship to clinical and
      biochemical patient characteristics. METHODS: Using a specific and sensitive
      kinetic ELISA, suPAR levels were determined in preoperative citrate plasma
      samples from 53 ovarian, 34 endometrial, and 30 cervical cancer patients, 17
      patients with benign ovarian tumors, and 28 patients with benign endometrial
      diseases. In addition, suPAR was measured in citrate samples from 31 female blood
      donors. RESULTS: suPAR was measurable in all samples. No significant difference
      was found between plasma suPAR in the blood donors and the patients with benign
      diseases (P = 0.58). The groups of cancer patients had suPAR levels that were
      significantly higher than those found in the blood donors (P < 0.0001, P <
      0.0001, and P = 0.001 for patients with ovarian, endometrial, and cervical
      cancer, respectively). In all groups of cancer patients a trend toward increasing
      suPAR levels with increasing FIGO stage was noted (P = 0.0003, P = 0.02, and P =
      0.01 for patients with ovarian, endometrial, and cervical cancer, respectively).
      Using the median suPAR level to dichotomize the ovarian cancer patients, FIGO
      stages I-III, a significantly increased risk of progression/relapse was found for
      patients with high suPAR levels (Hazard ratio (HR) = 3.1, 95% CI: 1.1-8.8, P =
      0.03). A multivariate analysis was performed, including suPAR, FIGO stage, and CA
      125. Only FIGO stage III compared with FIGO stage I was significant (HR = 15, 95%
      CI: 1.8-129, P = 0.01). Survival analyses were not performed in the endometrial
      or cervical cancer patients due to few progressions/relapses during the follow-up
      period. CONCLUSION: This study concludes that patients with gynecological cancers
      have elevated plasma suPAR levels as compared with healthy female blood donors
      and patients with benign gynecological diseases. In addition, high preoperative
      plasma levels of suPAR are significantly associated with poor outcome of ovarian
      cancer patients. However, additional studies are needed to further validate the
      clinical usefulness of plasma suPAR measurements in the management of ovarian
      cancer patients.

PMID- 11520151
TI  - Identification of prognostic factors in advanced epithelial ovarian carcinoma.
AB  - OBJECTIVE: The Gynecologic Oncology Group (GOG) has demonstrated that age, tumor
      grade, and size and number of residual lesions after primary cytoreductive
      surgery are significant prognostic factors in advanced ovarian carcinoma. Recent
      studies have reported numerous other clinical features as having prognostic
      value. We sought to identify the independent prognostic factors for survival in a
      cohort of patients with advanced ovarian cancer. METHODS: We performed a
      retrospective chart review of all patients with stage III and IV ovarian
      carcinoma who received their primary treatment at our institution between 1987
      and 1994. RESULTS: A total of 295 patients were identified, 282 of whom were
      evaluable. Of these 282 patients, 214 (76%) have died of disease or other causes.
      The median follow-up is 32 months (range: 1-139). Eighteen factors were evaluated
      for prognostic significance. Significant factors in univariate analysis included
      patient age, gravidity (0 vs > 0), parity (0 vs > 0), preoperative albumin level,
      preoperative total protein level, ascites (presence vs absence), disease stage
      (IIIA/IIIB vs IIIC vs IV), number of residual lesions (< or =20 vs >20), and
      diameter of largest residual tumor nodule (< or = 1 cm vs 1-2 cm vs > 2 cm).
      However, on multivariate analysis, only patient age (P < 0.001), ascites (P =
      0.001), and size of residual disease (P = 0.005) retained prognostic
      significance. Substage of disease was of borderline significance (P = 0.086).
      CONCLUSION: Although numerous clinical variables have recently been reported to
      have prognostic value in advanced ovarian carcinoma, only patient age, presence
      or absence of ascites, and diameter of the largest residual tumor nodule proved
      to be of statistical significance in our analysis.

PMID- 11520152
TI  - Intraoperative electron beam radiotherapy during radical surgery for locally
      advanced and recurrent cervical cancer.
AB  - OBJECTIVE: The goal of this study was to determine the toxicity patterns and
      clinical usefulness of intraoperative electron beam radiotherapy (IOERT) in
      patients with unfavorable-outcome cervical cancer. METHODS: From January 1986 to
      June 1999, 67 patients (36 recurrent, 31 primary disease) were treated with
      IOERT. Previously unirradiated patients received preoperative chemoradiation to
      45 Gy with cisplatin 20 mg/m(2) and 5-fluorouracil 1000 mg/m(2). IOERT median
      dose was 12 Gy for primary disease (range: 10-25) and 15 Gy for recurrent disease
      (range: 10-20). RESULTS: The 10-year control rate within the area treated with
      IOERT ("in-field" (IF)) for the entire group was 69.4, with 92.8 and 46.4% 10
      year IF control rates for the primary and recurrent patients, respectively. IF
      control rate correlated with involvement of the parametrial margin (P = 0.001),
      amount of residual disease (P = 0.001), and pelvic lymph node involvement (P =
      0.032). The overall incidence of toxic events that might be attributable to IOERT
      was 14.9%. Chronic pain was observed in 8 of 67 evaluable patients (11.9%) and
      motor neuropathy of the lower extremity in one patient (3.2%). CONCLUSIONS: IOERT
      is a valuable boosting technique in the management of advanced but resectable
      cervical cancer. Patients, especially recurrent cases, with positive lymph nodes,
      parametrial involvement, and/or incomplete resections have poor local control
      rates despite IOERT at the doses used in this study.

PMID- 11520153
TI  - Effects of melatonin on the proliferation and cis-diamminedichloroplatinum (CDDP)
      sensitivity of cultured human ovarian cancer cells.
AB  - OBJECTIVES: In this study, we investigated the antiproliferative effect and
      telomerase activity of melatonin with or without cis-diamminedichloroplatinum
      (CDDP) on CDDP-sensitive HTOA cells and CDDP-resistant OVCAR-3 cells of cultured
      human ovarian cancer. METHODS: HTOA cells and OVCAR-3 cells were cultured in RPMI
      1640 at 37 degrees C with 5% CO(2) for 132 h. To examine the antiproliferative
      effect of melatonin, cells were cultured with or without melatonin (10(-12)-10(
      6) M) and thereafter counted in a 96-well microplate using the alamarBlue assay.
      To examine the effect of melatonin and CDDP, cells were divided into group A
      (intermittent CDDP, 0.5 microg/ml), group B (intermittent CDDP + melatonin), and
      group C (sequential (12-h interval) CDDP/melatonin) and thereafter counted in a
      96-well microplate using the alamarBlue assay. In different series, cells were
      cultured and treated with either ethanol, melatonin, CDDP, or CDDP + melatonin.
      After harvest, telomerase activity was semiquantified with a fluorescence-based
      telomeric repeat amplification protocol (F-TRAP). RESULTS: (1) Melatonin produced
      no antiproliferative effect on both types of ovarian cancer cells. (2) Melatonin
      10(-6) M induced the antiproliferative effect in groups B and C compared with
      group A in the HTOA cell line. (3) Melatonin 10(-9) M produced the
      antiproliferative effect in groups B and C compared with group A in the OVCAR-3
      cell line. (4) Telomerase activity in the HTOA cell line did not change but, in
      the OVCAR-3 cell line, was significantly lower in the CDDP + melatonin group
      compared with the ethanol and CDDP groups. CONCLUSIONS: Melatonin enhanced CDDP
      sensitivity in two ovarian cancer cell lines. Thus, melatonin may improve ovarian
      cancer chemotherapy.

PMID- 11520154
TI  - Hypersensitivity reactions and the utility of oral and intravenous
      desensitization in patients with gynecologic malignancies.
AB  - OBJECTIVES: The aims of this study were to characterize hypersensitivity
      reactions to chemotherapy in patients with gynecologic malignancies and to
      determine the utility of oral and intravenous desensitization. METHODS: We
      retrospectively reviewed patients with hypersensitivity reactions identified by
      direct physician query and by review of charts with ICD9 code E933.1 (Adverse
      Effect Anti-Neoplastic). RESULTS: Thirty-two patients were identified: 27 with
      ovarian cancer, 4 with primary peritoneal cancer, and 1 with cervical cancer.
      Nine patients experienced hypersensitivity reactions during the primary regimen
      and 23 during chemotherapy for recurrent disease. Hypersensitivity occurred
      following an average of nine courses. Hypersensitivity occurred secondary to
      paclitaxel (10) carboplatin (16), cisplatin (4), bleomycin (1), and
      paclitaxel/carboplatin combination therapy (1). Patients had previously received
      the agent in 93.8% of carboplatin reactions, in 54.5% of paclitaxel reactions,
      and in all other agent reactions. Hypersensitivity reactions most commonly
      included flushing, dyspnea/bronchospasm, back pain, chest discomfort, pruritus,
      erythema, and nausea and occasionally included alterations in blood pressure or
      pulse rate. Reactions were successfully treated in 96.9% of patients by
      interrupting the infusion and administering steroids, antihistamines,
      benzodiazepines, nebulized beta-agonists, and/or pressors. Seventeen patients
      underwent desensitization, one to two agents, with 94% success. Nine of ten
      patients had successful iv desensitization, and 8/10 patients had successful oral
      desensitization. One failure on the oral regimen had previous successful iv
      desensitization. CONCLUSIONS: Hypersensitivity reactions to chemotherapeutic
      agents do not necessarily require exclusion of a compound from the treatment
      regimen. Intravenous and oral desensitization protocols are useful for successful
      and safe administration of paclitaxel and platinum compounds in patients with
      prior hypersensitivity reactions.

PMID- 11520155
TI  - Limb preservation by Gore-Tex vascular graft for groin recurrence after
      postoperative adjuvant radiation in vulvar cancer.
AB  - BACKGROUND: Recurrent vulvar cancer involving the femoral artery after groin
      radiation is usually considered inoperable. A patient with such recurrent vulvar
      cancer successfully treated by femoral vascular graft and rectus abdominis
      myocutaneous flap reconstruction with limb salvage is described. CASE: A 51-year
      old woman had recurrent vulvar cancer involving the right femoral vessels 6
      months after a radical vulvectomy plus inguinal lymphadenectomy and postoperative
      pelvic and groin radiation. Radical en bloc excision of tumor along with the
      involved femoral artery and vein followed by Gore-Tex vascular graft and rectus
      abdominis myocutaneous flap reconstruction led to a complete remission. However,
      occlusion of the grafted vessels occurred 21 months following bypass surgery.
      Since the compensatory collaterals were established, debridement and removal of
      the occluded graft were carried out. The patient has been clinically free of
      disease for more than 48 months since graft reconstruction surgery. CONCLUSION:
      It is highlighted that aggressive tumor resection with limb salvage is feasible
      even for patients with vulvar cancer of the groin recurrence involving the
      femoral artery after primary surgery and groin radiation.

PMID- 11520156
TI  - Carcinosarcoma of the uterus: immunohistochemical and genetic analysis of
      clonality of one case.
AB  - BACKGROUND: Carcinosarcomas of the uterus are characterized by admixtures of
      malignant epithelial and stromal cells, and their histogenesis remains
      controversial. CASE: An operated case of carcinosarcoma of the uterus in a 49
      year-old woman is reported with clonal analysis. The tumor was composed of
      carcinomatous, sarcomatous, and transitional elements in the frontal wall of the
      uterine body and therefore was diagnosed as a carcinosarcoma. On
      immunohistochemical analysis, the sarcomatous component proved negative for
      epithelial membrane antigen and keratin while both components were positive for
      vimentin. Analysis of X-chromosome inactivation showed the same pattern
      throughout and additionally, the same K-ras and p53 mutations were homogeneously
      detected. Microsatellite instability analysis showed loss of heterozygosity at
      D5S346 in the sarcomatous but not the carcinomatous component. CONCLUSIONS: This
      tumor appears monoclonal in line with the combination tumor theory, with late
      divergence in genetic alteration in the sarcomatous elements.

PMID- 11520157
TI  - Perineal excision of a large angiomyxoma in a young woman following magnetic
      resonance and angiographic imaging.
AB  - BACKGROUND: Aggressive angiomyxomas are rare, arise from connective tissue of the
      perineum or the lower pelvis, and affect predominantly young women. CASE: We
      describe an unusual case of aggressive angiomyxoma in which the perineal approach
      was possible owing to MRI scanning and selective angiography indications.
      CONCLUSION: In cases of large aggressive angiomyxomas these diagnostic procedures
      should make it possible to decide which operative route might be best for the
      patient.

PMID- 11520158
TI  - Microcystic adnexal carcinoma of the vulva.
AB  - BACKGROUND: Microcystic adnexal carcinoma (MAC) is a subset of sweat gland
      carcinoma first described as a specific entity by D. J. Goldstein, R. J. Barr,
      and D. J. Santa Cruz (Cancer 1982;50:566-72). We report the first case of MAC
      occurring on the vulva and review the literature pertaining to this rare tumor.
      CASE: A 43-year-old multiparous black woman presented initially to Kings County
      Hospital Medical Center with a chief complaint of a vulvar lesion arising on the
      left labia majora which she had noted for 4 years prior to presentation. Aside
      from increasing paresthesia in the area, she denied any constitutional symptoms.
      Her past medical history was significant only for hyperthyroidism and mild
      hypertension and surgical history was noncontributory. Gynecologic history was
      unremarkable, with sporadic care over the last 20 years. Physical examination
      revealed a 1.5 x 2.0-cm raised, well-circumscribed, firm mobile lesion on the
      left labia majora. It was noted to be yellow in color with the surrounding tissue
      being unremarkable in character. The remainder of her gynecologic examination and
      lymph node survey was unremarkable. Preoperative chest X ray was negative as was
      the CAT scan of the abdomen and pelvis. All laboratory values were within normal
      limits. A Pap smear done preoperatively was significant for atypical squamous and
      glandular cells of undetermined significance. Subsequent colposcopic examination
      of the cervix was remarkable for cervicitis and was adequate, with the entire
      transformation zone visualized. Both endocervical curettage and endometrial
      biopsy were normal. Initially, an excisional biopsy was performed with final
      pathology demonstrating microcystic adnexal carcinoma with positive surgical
      margins. She subsequently underwent a left radical hemivulvectomy with bilateral
      inguinal groin lymph node dissection. At the time of surgery, the left labia
      majora was noted to be well healed, with a residual surgical scar easily
      discernible. No areas of discoloration were noted and digital palpation of the
      area was unremarkable. Microscopic residual tumor was noted; however, all
      surgical margins and lymph nodes were negative for tumor. Her postoperative
      course was unremarkable. The patient has continued to do well since the time of
      her surgery and is being followed conservatively. CONCLUSION: Radical vulvectomy
      should be performed when MAC occurs in the vulva to secure negative margins of
      resection. Groin dissection should be reserved for cases in which the inguinal
      lymph nodes are clinically suspicious or in cases of tumor recurrence.

PMID- 11520159
TI  - Malignant struma ovarii with thyrotoxicosis.
AB  - BACKGROUND: Malignant struma ovarii is seldom diagnosed preoperatively due to the
      rarity of the disease itself and the even rarer complications of thyrotoxicosis.
      CASE: A 48-year-old woman presented with symptoms of hyperthyroidism and a pelvic
      tumor raising the possibility of ovarian malignancy. Hormonal findings revealed
      increased thyroid function, but the thyroid gland was normal in size and texture.
      Thus, she was diagnosed preoperatively as having a hormone-producing malignant
      struma ovarii. At surgery, a FIGO stage Ia ovarian papillary adenocarcinoma of
      the thyroid was found. An immunohistochemical tumor stain for thyroglobulin was
      positive and the ovarian venous thyroglobulin level was extremely high. Findings
      of hyperthyroidism disappeared over several weeks. CONCLUSION: Malignant struma
      ovarii can be diagnosed preoperatively. Complications of thyrotoxicosis should be
      kept in mind when evaluating an ovarian tumor.

PMID- 11520160
TI  - Sustained complete remission in a patient with platinum-resistant ovarian yolk
      sac tumor.
AB  - BACKGROUND: Yolk sac tumors of the ovary are generally very responsive to
      chemotherapy; however, they are difficult to manage in the setting of platinum
      resistance where treatment options are limited and outcomes are poorer. CASE: We
      present a 39-year-old woman who had a platinum-resistant yolk sac ovarian tumor.
      She achieved complete remission on an innovative regimen of docetaxel,
      gemcitabine, and thalidomide. CONCLUSION: The combination of docetaxel,
      gemcitabine, and thalidomide might be an active regimen for platinum-resistant
      ovarian nondysgerminomas and further investigation of this combination is
      warranted.

PMID- 11520161
TI  - Light-based imaging of green fluorescent protein-positive ovarian cancer
      xenografts during therapy.
AB  - OBJECTIVE: The purpose of the study was to develop a sensitive, noninvasive
      imaging method for monitoring ovarian xenografts during therapeutic intervention.
      METHODS: Human ovarian tumor cells (SKOV3.ip1) were infected with a replication
      deficient adenoviral (Ad) vector encoding green fluorescent protein (GFP). The
      GFP-positive tumor cells were imaged in vitro and in vivo with a fluorescence
      stereomicroscope. Using appropriate filters, both GFP fluorescence and adriamycin
      were simultaneously detected. Nude mice implanted with GFP-positive cells were
      imaged repeatedly, in a noninvasive manner. RESULTS: SKOV3.ip1 cells infected
      with Ad-GFP showed high GFP fluorescence, which was eliminated after treatment
      with adriamycin. Loss of GFP fluorescence was confirmed to be dead cells. For in
      vivo imaging, intraperitoneal tumors as small as 0.2 mm in diameter were detected
      externally. Adriamycin uptake was detected in tumors by in vivo imaging, and
      reduction in tumor size was concurrent with decrease in GFP fluorescence. These
      findings were confirmed at necropsy. CONCLUSIONS: Fluorescence stereomicroscopy
      monitored the response of ovarian xenografts to adriamycin therapy. For the first
      time, GFP and adriamycin were imaged simultaneously.

PMID- 11520162
TI  - Re: Aziz S, et al. A genetic epidemiological study of carcinoma of the Fallopian
      tube. Gynecol Oncol 2001;80:341-5.

PMID- 11520163
TI  - Modern patient management in rheumatology: interventional musculoskeletal
      ultrasonography.

PMID- 11520164
TI  - Guidance by ultrasound of intra-articular injections in the knee and hip joints.
AB  - OBJECTIVE: To develop and assess a stable method for ascertaining the placement
      of intraarticular injections for osteoarthritis (OA) in the hip and knee.
      METHODS: Injections into the hip or knee joint with e.g. hyaluronan or cortisone
      were performed under the guidance of ultrasound. For this purpose an Acuson
      Sequoia apparatus and a 8-15 MHz transducer were used. After perforation of the
      capsule with a 21 G needle, 0.5-1 ml of atmospheric air and 1 ml lidocain 1% was
      injected with simultaneous recording of the ultrasound signals. This procedure
      was undertaken before the injection of the medication through the in situ needle.
      RESULTS: In the hip joint the injected air could readily ascertain the placement
      of the injection with a sharp echoic contrast forming on the ultrasound picture
      respecting the joint cavity. In the knee joint the procedure gave the best
      results in joints which have a small amount of fluid in either the suprapatellar
      bursa or in a pouch regularly observed over the lateral joint margin. However,
      also in some so-called 'dry' knee joints the air could be traced in the bursa by
      ultrasound. CONCLUSION: By the injection of air, it is possible to test the
      placement of intraarticular injections in both hip and knee joints. This
      procedure will give a supplementary documentation of the injection as compared to
      a mere ultrasonographic demonstration of the position of the needle in the joint.
      The method is proposed as a tool for both learning purposes and quality assurance
      in daily therapy.

PMID- 11520165
TI  - ATP induces Ca(2+) signaling in human chondrons cultured in three-dimensional
      agarose films.
AB  - OBJECTIVE: In vivo, chondrocytes are surrounded by an extracellular matrix,
      preventing direct cell-to-cell contact. Consequently, intercellular communication
      through gap junctions is unlikely. However, signaling at a distance is possible
      through extracellular messengers such as nitric oxide (NO) and nucleotides and
      nucleosides, adenosine triphosphate (ATP), uridine triphosphate (UTP), or
      adenosine diphosphate (ADP). We hypothesized that chondrons, chondrocytes
      surrounded by their native pericellular matrix, increase their intracellular
      calcium concentration ([Ca(2+)]ic) in response to ATP and other signaling
      molecules and that the source of Ca(2+) is from intracellular stores. The
      objectives of this study were to determine if chondrons in a 3-D gel respond to
      ATP by increasing [Ca(2+)]ic through a purinoceptor mechanism and to test whether
      chondrons in whole tissue samples would respond to ATP in a similar fashion.
      DESIGN: Human chondrons, cultured in a three-dimensional agarose gel or in whole
      cartilage loaded with Fura-2AM, a calcium sensitive dye, were stimulated with 1,
      5 and 10 microM ATP. A ratio-imaging fluorescence technique was used to
      quantitate the [Ca(2+)]ic. RESULTS: ATP-stimulated chondrons increased their
      [Ca(2+)]ic from a basal level of 60 nM to over 1000 nM. Chondrons incubated in
      calcium-free medium also increased their [Ca(2+)]ic in response to ATP,
      indicating the source of Ca(2+) was not extracellular. ATP-induced calcium
      signaling was inhibited in chondrons pre-treated with suramin, a generic
      purinoceptor blocker. In addition, UTP and adenosine 5'-O-(3-thiotriphosphate)
      (ATPgammas) induced a calcium response, but 2-methylthio-ATP (2-MeSATP), ADP, and
      adenosine did not induce a significant increase in [Ca(2+)]ic, substantiating
      that the P2Y2 purinoceptor was dominant. Chondrons in whole cartilage increased
      [Ca(2+)]ic in response to ATP. CONCLUSIONS: We conclude that chondrons in 3-D
      culture respond to ATP by increasing [Ca(2+)]ic via P2Y2 receptor activation.
      Thus, ATP can pass through the agarose gel and the pericellular matrix, bind
      purinoceptors and increase intracellular Ca(2+) in a signaling response.

PMID- 11520166
TI  - The experience of pain and emergent osteoarthritis of the knee.
AB  - Discrepancies exist between radiographic osteoarthritis of the knee (OAK) and
      report of knee joint pain. Little is known about how these two definitions of
      osteoarthritis (OA) and their correlates differ between African American (AA) and
      Caucasian (CA) women. OBJECTIVE: We compared the prevalence of radiographic OAK
      and knee joint pain in AA and CA women, and the congruency of these outcomes
      according to age, body size, and knee injury. DESIGN: A cross-sectional study of
      African American and Caucasian women aged 40-53 years (N=829) in Southeast
      Michigan used the Kellgren and Lawrence Atlas of Standard Radiographs of
      Arthritis to characterize radiographs of both knee joints (weight bearing) and
      self-report of knee pain. RESULTS: Current pain was a significantly more
      sensitive predictor of radiographic OAK among AA women (Se=0.51) compared to CA
      women (Se=0.35). Specificity was similar between AA women (Sp=0.77) and CA women
      (Sp=0.82). Positive predictive value was significantly greater for AA compared
      with CA women (PV+=0.40 and PV+=0.15, respectively). The odds of having
      radiographic OAK increased with BMI >32 kg/m(2) in both groups. Knee pain was
      related to BMI in CA women, but not AA women. Previous knee injury was associated
      with knee pain in both AA and CA women (OR=3.0 and OR=2.4). CONCLUSIONS: Joint
      pain in AA women was more likely to be associated with radiographic OAK as
      compared with CA women. This suggests differences in these two groups in both how
      pain is experienced in the OAK process and in the prevalence of non-OAK related
      pain in knee joints.

PMID- 11520167
TI  - Water distribution patterns inside bovine articular cartilage as visualized by 1H
      magnetic resonance imaging.
AB  - OBJECTIVE: To develop a magnetic resonance imaging (MRI) technique to non
      invasively map water volume fraction (WVF) in articular cartilage. Special
      emphasis was placed on spatial resolution and temporal considerations, aimed at
      creating a procedure feasible for eventual human studies. DESIGN: Absolute proton
      density MR images of intact, ex vivo bovine patellae were calculated from fully
      T(1) relaxed, short echo time images. This was accomplished through compensation
      for T(2) decay with calculated T(2) maps. Calibration of the signal intensity in
      the image was accomplished with the use of H2O:D2O phantoms, where the WVF was
      varied from 0.95 to 0.75. Application of the calibration curve to the entire
      image yielded images that represent WVF on a pixel by pixel basis. Calculations
      of water content by weight were performed by considering the density of the solid
      content. RESULTS: Using four echo time points, experiments comparing MR images
      from single-echo and multi-echo spin echo sequences yielded similar results. T(2)
      decreased with depth through the cartilage, with a maximum at the articular
      surface of approx 100 ms, and a approximately 50 ms minimum at the bone/cartilage
      interface. The WVF through the depth of the cartilage showed a similar trend,
      decreasing from 0.9 at the surface, to 0.7 at the bone/cartilage interface.
      Translation to a weight percent yielded approximately 86% weight at the surface,
      trending down to approximately 63% at the bone/cartilage interface, with an
      average of 74.5% for five patellae. These MRI derived values were compared to the
      measured weight of water in excised cartilage plugs from the same patellae and
      showed remarkably close agreement. CONCLUSION: We have demonstrated that MRI can
      non-invasively map WVF in cartilage in a pixel by pixel manner. This was
      accomplished in a time span that was clinically feasible, allowing the routine
      use of this method in a clinical setting. Moreover, this procedure employed
      standard MRI equipment and pulse sequences, avoiding the need for hardware
      modifications and using simple post processing methods. However, baseline studies
      need to be performed prior to incorporation into a standard radiological
      evaluation. Implications in the diagnosis of osteoarthritis (OA) are discussed.

PMID- 11520168
TI  - The role of ADAM-TS4 (aggrecanase-1) and ADAM-TS5 (aggrecanase-2) in a model of
      cartilage degradation.
AB  - INTRODUCTION: Cleavage of aggrecan between residues Glu(373)-Ala(374), which is
      believed to be a key event in aggrecan destruction in arthritic diseases, has
      been attributed to an enzymatic activity, aggrecanase. Two cartilage aggrecanases
      have been identified, aggrecanase-1 (ADAM-TS4) and aggrecanase-2 (ADAM-TS5) and
      both enzymes have been shown very efficiently to cleave soluble aggrecan at the
      Glu(373)-Ala(374) site. OBJECTIVE: To determine whether ADAM-TS4 and/or ADAM-TS5
      are the aggrecanases responsible for aggrecan catabolism following interleukin-1
      (IL-1) and tumor necrosis factor (TNF) treatment of bovine articular cartilage.
      RESULTS: (1) IL-1- and TNF-stimulated release of aggrecan was associated with
      cleavage of aggrecan within the C-terminus at the ADAM-TS4 and ADAM-TS5-sensitive
      sites, Glu(1480)-Gly(1481), Glu(1667)-Gly(1668), and Glu(1871)-Leu(1872). (2) The
      order of cleavage following IL-1 stimulation of cartilage explants was the same
      as when soluble aggrecan is digested with recombinant human ADAM-TS4 and ADAM
      TS5. (3) Both constitutive and stimulated cleavage of aggrecan at the ADAM-TS4
      and ADAM-TS5-sensitive sites in cartilage was blocked by a general
      metalloproteinase inhibitor but not by a MMP-specific inhibitor, and this
      inhibition correlated with inhibition of aggrecan release from cartilage. (4) PCR
      and Western blot analysis indicated that both ADAM-TS proteases are expressed in
      cartilage explants; ADAM-TS5 is constitutively expressed whereas ADAM-TS4 is
      induced following IL-1 and TNF treatment. (5) Immunodepletion of both ADAM-TS4
      and ADAM-TS5 from bovine articular cartilage cultures following IL-1 stimulation
      resulted in a 90% reduction of aggrecanase activity in the culture medium.

PMID- 11520169
TI  - Distribution of aggrecanase (ADAMts 4/5) cleavage products in normal and
      osteoarthritic human articular cartilage: the influence of age, topography and
      zone of tissue.
AB  - OBJECTIVE: To develop and characterize a polyclonal antiserum (RAM 3.2), which
      recognizes the neo-C terminal cleavage product generated by the action of
      aggrecanase (ADAMts 4/5) on the G1-domain of human aggrecan. We also intend to
      use this antiserum to investigate normal, age-related changes in human articular
      cartilage. METHOD: The antiserum was raised in rabbits and its localization in
      cryosections of normal articular cartilage was investigated by
      immunohistochemistry. The concentration of the aggrecanase neo-epitope was also
      investigated in extracts of the tissue using SDS-PAGE and electrophoresis in
      large pore/agarose gels. RESULTS: The product of aggrecanase action appears to
      accumulate in the extracellular matrix during normal aging of the tissue.
      Furthermore, the concentration of the fragment depended on the topographical site
      on the femoral condyle from which the sample was selected. Electrophoretic and
      immunohistochemical analysis of the fragment in normal cartilage showed that in
      immature cartilage it was deposited mainly in the surface layers, whereas in
      mature samples it was distributed throughout the depth of the tissue. In
      contrast, immunoreactivity of osteoarthritic cartilage was always less and the
      distribution was more variable than in normal cartilage of the same age.
      CONCLUSIONS: (1) The proteolytic cleavage of aggrecan by aggrecanase is a normal
      homeostatic event and much of the neo-C terminal fragment produced by the enzyme
      is retained in the tissue. (2) The presence of this immunoreactive product in
      normal cartilage can be used as an indication of aggrecan turnover. (3) That in
      osteoarthritic cartilage there is a reduction in the concentration of the G1
      fragments.

PMID- 11520170
TI  - Depth-dependent compressive properties of normal aged human femoral head
      articular cartilage: relationship to fixed charge density.
AB  - OBJECTIVES: Determine the depth-varying confined and osmotic compression moduli
      of normal human articular cartilage from the femoral head, and test whether these
      moduli are dependent on fixed charge density. METHODS AND RESULTS: Using an
      automated instrument to allow epifluorescence microscopy analysis during confined
      compression testing on cartilage samples, the equilibrium confined compression
      modulus (H(A 0)) was found to vary markedly with depth (z=0-1500 microm) from the
      articular surface. H(A 0) increased from 1.16+/-0.20 MPa in the superficial (0
      125 microm) layer to 7.75+/-1.45 MPa in the deepest (1250-1500 microm) layer
      tested, and was fit by the expression, H(A 0)(z) [MPa]=1.44 exp(0.0012.z
      [microm]). Also, in successive slices of cartilage extending from the articular
      surface to the middle-deep regions, the bulk modulus (K(0)) and fixed charge
      density (FCD) increased, consistent with previous findings. While H(A 0), K(0),
      and FCD each varied with depth from the articular surface, the dependence of H(A
      0) and K(0) on depth did not appear to be completely related to variations in
      FCD. CONCLUSIONS: The confined compression modulus of normal aged human femoral
      head articular cartilage increases markedly with depth from the articular
      surface, a trend similar to that observed for articular cartilage from other
      joints in animals but with an absolute amplitude that is several-fold higher. The
      compressive properties were not simply related to FCD at different depths from
      the articular surface, suggesting that other as yet undefined factors also
      contribute to compressive properties.

PMID- 11520171
TI  - Reliability, validity, and sensitivity to change of the Cochin hand functional
      disability scale in hand osteoarthritis.
AB  - OBJECTIVE: To assess the reliability, validity and sensitivity to change of the
      Cochin hand functional scale in hand osteoarthritis (OA). BACKGROUND: The Cochin
      hand functional disability scale has been validated in rheumatoid arthritis.
      DESIGN: Patients with hand OA according to Altman's criteria were included.
      Impairment outcome measures (VAS of pain, hand score of tenderness, clinical hand
      score of impairment, Kallman's radiographic scale), functional disability
      measures [Cochin scale, Revel's functional index (RFI), Dreiser's functional
      index (DFI)] and patients' perceived handicap (VAS) were recorded twice, at
      baseline and at a 6-month follow-up visit. Interobserver reliability was assessed
      using the intraclass correlation coefficient (ICC) and the Bland and Altman
      method. Construct (convergent and divergent) validity was investigated using the
      Spearman rank correlation coefficient and a factor analysis was performed.
      Sensitivity to change was assessed using the effect size (ES) and the
      standardized response mean (SRM), and the non-parametric Spearman rank
      correlation coefficient (r) was used to assess the correlation between
      quantitative variable changes and patient's overall opinion. RESULTS: 89 patients
      (8 males, mean age 63 years) were included. Interobserver reliability was
      excellent (ICC=0.96). The Bland and Altman method showed no systematic trend.
      Correlations of the Cochin scale score with RFI (r=0.86), DFI (r=0.87), VAS of
      handicap (r=0.67), VAS of pain (r=0.54), tenderness (r=0.51), clinical impairment
      (r=0.32), and Kallman's radiographic scale (r=0.13) indicated a good construct
      validity. Factor analysis extracted four main factors, accounting for 65% of the
      total variance. 51 patients were evaluated at the 6-month visit. The Cochin scale
      score had worsened with SRM and ES values of -0.26 and -0.17 respectively.
      Changes in the score had one of the highest correlation (r=0.47) with the
      patient's overall opinion. CONCLUSION: The Cochin hand functional disability
      scale which was first developed to assess the rheumatoid hand can be used to
      evaluate functional disability in hand OA.

PMID- 11520172
TI  - The transglutaminase, Factor XIIIA, is present in articular chondrocytes.
AB  - OBJECTIVES: The transglutaminase (TGase) family includes seven different enzymes
      that catalyse a protein cross-linking reaction resulting in structural and
      functional alterations in substrate proteins. TGase activity is easily
      measureable in mature articular cartilage where it may contribute to CPPD
      deposition disease through its actions on growth factors, crystal components or
      extracellular matrix proteins. In contrast, low levels of TGase activity are
      found in chondrocytes from young animals. We previously demonstrated type II
      TGase protein in articular chondrocytes. Earlier work also suggested the presence
      of another form of TGase in chondrocytes. We sought to determine if articular
      chondrocytes contain the TGase, Factor XIIIA (FXIIIA). METHODS: Western blots
      with FXIIIA antibody were used to detect FXIIIA in young and old porcine
      articular chondrocytes and articular cartilage vesicles (ACVs). The presence of
      FXIIIA mRNA was confirmed by RT-PCR. RESULTS: Old chondrocyte conditioned medium,
      cytosol, and membrane fractions contained FXIIIA protein on Western blots, while
      less FXIIIA was detectable in cell fractions or media from young chondrocytes.
      ACVs also contained FXIIIA. FXIIIA mRNA was demonstrated by PCR in old and young
      chondrocytes. CONCLUSIONS: FXIIIA is present in articular chondrocytes. FXIIIA
      levels correlate with TGase activity in chondrocytes. The presence of two forms
      of TGase in articular chondrocytes suggest an important function for this enzyme
      family in articular cartilage.

PMID- 11520173
TI  - In situ compressive stiffness, biochemical composition, and structural integrity
      of articular cartilage of the human knee joint.
AB  - OBJECTIVE: Reduction of compressive stiffness of articular cartilage has been
      reported as one of the first signs of cartilage degeneration. For the measurement
      of in situ compressive stiffness, a hand-held indentation probe has recently been
      developed and baseline data for macroscopically normal knee joint cartilage were
      provided. However, the histological stage of degeneration of the measured
      cartilage was not known. The purpose of this study was to investigate whether
      there is a relationship between the in situ measured compressive stiffness, the
      histological stage of degeneration, and the biochemical composition of articular
      cartilage. DESIGN: Instantaneous compressive stiffness was measured for the
      articular cartilage of 24 human cadaver knees. Additionally, biochemical
      composition (total proteoglycan and collagen content) and histological appearance
      (according to the Mankin score) were assessed for each measurement location.
      RESULTS: Despite visually normal surfaces, various histological signs of
      degeneration were present. A high correlation between Mankin score and cartilage
      stiffness was observed for the lateral patellar groove (R(2)=0.81), the medial
      (R(2)=0.83) and the lateral femoral condyle (R(2)=0.71), whereas a moderate
      correlation was found for the medial patellar groove (R(2)=0.44). No correlation
      was observed between biochemical composition and cartilage compressive stiffness.
      CONCLUSIONS: Our results are in agreement with others and show that the
      instantaneous compressive stiffness is primarily dependent on the integrity of
      the extracellular matrix, and not on the content of the major cartilage
      constituents. The high correlation between stiffness and Mankin score in mild
      osteoarthrosis suggests that the stage of cartilage degeneration can be assessed
      quantitatively with the hand-held indentation probe. Moderate and severe case of
      osteoarthrosis remains to be investigated.

PMID- 11520174
TI  - The genetic contribution to hip joint morphometry and relationship to hip
      cartilage thickness.
AB  - A twin study approach was used to explore the genetic determinants of hip joint
      morphometry and their relationship to hip cartilage thickness. Our analysis used
      data on anthropometric characteristics and radiographic features of a group of
      222 monozygotic (MZ) and 240 dizygotic (DZ) twins. We confirmed that genetic
      factors account for most of the variation in minimal joint space (MJS) and
      acetabular anatomy. This genetic variation was largely due to factors unique to
      MJS itself and not explained by anthropometric variables or measurements of
      acetabular morphology. Only a small proportion was shared with genetic factors
      underlying acetabular shape, mainly the centre edge angle.

PMID- 11520175
TI  - Neuronal trafficking of palmitoyl protein thioesterase provides an excellent
      model to study the effects of different mutations which cause infantile neuronal
      ceroid lipofuscinocis.
AB  - Infantile neuronal ceroid lipofuscinosis (INCL) is a severe neurodegenerative
      storage disorder in children caused by mutations in the palmitoyl protein
      thioesterase gene (PPT1). We have investigated here four naturally occurring
      previously described PPT1 mutations and show that all cause severe effects on
      PPT1 enzyme activity in transiently transfected COS-1 cells. Two of the mutations
      (delPhe84 and insCys45) cause a classical INCL phenotype and two (Thr75Pro and
      Leu219Gln) result in a late onset disease phenotype. All these mutated PPT1
      molecules have severely altered intracellular localization in transiently
      transfected BHK-cells, whereas in mouse primary neuron cultures different effects
      were observed. In neurons the delPhe84 and insCys45 mutant polypeptides were
      targeted to the ER. Interestingly the Thr75Pro and Leu219Gln mutations had only
      minor effects on the neuronal trafficking of PPT1 and the mutated polypeptides
      were observed in neuronal shafts and showed colocalization with the presynaptic
      marker SV2. Our data indicates that neuronal cells provide an excellent model to
      study the genotype-phenotype correlation in INCL.

PMID- 11520176
TI  - Rhombomere interactions control the segmental differentiation of hindbrain
      neurons.
AB  - The embryonic hindbrain is subdivided into a series of metameric units termed
      rhombomeres, which display features that strongly suggest they are autonomous
      developmental units. However, some aspects of their phenotype develop
      nonautonomously. Here we have analyzed the possibility that interrhombomere
      interactions generate the pattern of segmental neuronal differentiation. The
      differentiation of both projection interneurons and motor neurons in the
      hindbrain is retarded in rhombomeres 3 and 5. We demonstrate here that if either
      rhombomere 3 or 5 is isolated from the influence of their neighbours, either in
      vitro or in vivo, then these segments no longer display delayed neuronal
      diufferentiation. We further show that the retardation of motor neurons
      differentiation in rhombomeres 3 and 5 is, at least in part, mediated by Bmp-4.
      If this molecule is inhibited, by grafting cells expressing chordin, then the
      motor neurons of these rhombomeres develop ahead of their normal schedule.

PMID- 11520177
TI  - The dynamics of SAP90/PSD-95 recruitment to new synaptic junctions.
AB  - SAP90/PSD-95 is thought to be a central organizer of the glutamatergic synapse
      postsynaptic reception apparatus. To assess its potential role during
      glutamatergic synapse formation, we used GFP-tagged SAP90/PSD-95, time lapse
      confocal microscopy, and cultured hippocampal neurons to determine its dynamic
      recruitment into new synaptic junctions. We report that new SAP90/PSD-95 clusters
      first appeared at new axodendritic contact sites within 20-60 min of contact
      establishment. SAP90/PSD-95 clustering was rapid, with kinetics that fit a single
      exponential with a mean time constant of approximately 23 min. Most new SAP90/PSD
      95 clusters were found juxtaposed to functional presynaptic boutons as determined
      by labeling with FM 4-64. No evidence was found for the existence of discrete
      transport particles similar to those previously reported to mediate presynaptic
      active zone cytoskeleton assembly. Instead, we found that SAP90/PSD-95 is
      recruited to nascent synapses from a diffuse dendritic cytoplasmic pool. Our
      findings show that SAP90/PSD-95 is recruited to nascent synaptic junctions early
      during the assembly process and indicate that its assimilation is fundamentally
      different from that of presynaptic active zone components.

PMID- 11520178
TI  - Caspase activity is involved in, but is dispensable for, early motoneuron death
      in the chick embryo cervical spinal cord.
AB  - We examined the role of caspases in the early programmed cell death (PCD) of
      motoneurons (MNs) in the chick embryo cervical cord between embryonic day (E) 4
      and E5. An increase in caspase-3-like activity in MNs was observed at E4.5.
      Treatment with an inhibitor of caspase-3-like activity, Ac-DEVD-CHO, for 12 h
      blocked this increase and revealed that caspase-3-like activity is mainly
      responsible for DNA fragmentation and the nuclear changes during PCD but not for
      degenerative changes in the cytoplasm. When a more broad-spectrum caspase
      inhibitor was used (bocaspartyl (OMe)-fluoromethyl ketone, BAF), the appearance
      of degenerative changes in the cytoplasm was delayed by at least 12 h. However,
      following treatment with either Ac-DEVD-CHO or BAF for 24 h, the number of
      surviving healthy MNs did not differ from controls, indicating a normal
      occurrence of PCD despite the inhibition of caspases. These results suggest that
      caspase cascades that occur upstream of and are independent of the activation of
      caspase-3-like activity are responsible for the degenerative changes in the
      cytoplasm of dying cervical MNs. These data also suggest that, although one
      function of caspases may be to facilitate the kinetics of PCD, caspases are
      nonetheless dispensable for at least some forms of normal neuronal PCD in vivo.

PMID- 11520179
TI  - Nerve growth factor modulates the activation status and fast axonal transport of
      ERK 1/2 in adult nociceptive neurones.
AB  - Mature dorsal root ganglion cells respond to neurotrophins, and the intracellular
      signalling pathways activated by neurotrophins have been characterized in vitro.
      We have now used immunocytochemistry and Western blots to examine the expression
      and activation of extracellular signal-regulated protein kinase-1/2 (ERK) in rat
      dorsal root ganglion cells in vivo, using antisera to total (tERK) and
      phosphorylated (pERK) forms. This has revealed a number of novel findings. tERK
      immunoreactivity is present in most dorsal root ganglion cells but is expressed
      most strongly in small (nociceptive) cells and, surprisingly, is absent in a
      population of large cells that expressed trkB or trkC but mainly lack p75(NTR)
      immunoreactivity. In contrast pERK is prominent in a few trkA cells and in
      satellite glial cells, and is further increased by NGF treatment. tERK and pERK
      both undergo fast anterograde and retrograde axonal transport, indicated by
      accumulation at a sciatic nerve ligature, and NGF reduces the level of retrograde
      pERK transport.

PMID- 11520180
TI  - Atypical neuroleptic drugs downregulate dopamine sensitivity in rat cortical and
      striatal astrocytes.
AB  - Psychotic symptoms in different neuropsychiatric disorders are treated by
      neuroleptic drugs. Neuroleptics are known to block dopamine (DA)
      neurotransmission, however, cell types mediating their actions have not been
      determined. Recently, astrocytes have been demonstrated to express D1- and D2-DA
      receptors, whose activation leads to transient increases in intracellular calcium
      concentration. We show here that DA-sensitivity of cortical and striatal rat
      astroglial cultures, as monitored by calcium imaging, is reduced by a 12-h
      exposure to the atypical antipsychotic agents Clozapine (>1 nmol/liter),
      Olanzapine (>100 nmol/liter), and Risperidone (>1 nmol/liter), but not by
      classical neuroleptics Haloperidol and Sulpiride. These effects could not be
      reverted by the receptor-specific antagonists SCH23390, Sulpiride, L745 870,
      Ergotamine, and Propranolol. In addition, RT-PCR and Western blot analyses
      concerning the effects of Clozapine, Olanzapine, and Risperidone on DA receptor
      expression in cortical and striatal astroglial cells revealed no alterations in
      mRNAs and immunoreactive protein of D1- and D2-DA receptor subtypes. These
      results provide the first evidence that atypical but not classical neuroleptic
      drugs reduce astroglial DA-sensitivity, a mechanism that may be important for a
      better understanding of differences in effects and side effects between atypical
      and classical neuroleptic drugs.

PMID- 11520181
TI  - The precursor pro-nerve growth factor is the predominant form of nerve growth
      factor in brain and is increased in Alzheimer's disease.
AB  - Nerve growth factor (NGF) is important for regulation, differentiation, and
      survival of peripheral and central nervous system neurons, including basal
      forebrain cholinergic neurons (BFCN) which degenerate in Alzheimer's disease
      (AD). Mature NGF protein is processed from a larger precursor, proNGF. We
      demonstrate that proNGF is the predominant form of NGF in mouse, rat, and human
      brain tissue, whereas little or no mature NGF is detected. Previous reports
      showed NGF protein, measured by ELISA, is increased in AD BFCN target regions
      such as hippocampus and cortex. Using Western blotting, we demonstrate a twofold
      increase in proNGF in AD parietal cortex compared to controls, indicating that it
      is this precursor form, proNGF, that accumulates in AD. This increase may reflect
      either a role for biologically active proNGF or posttranslational disturbances in
      NGF biosynthesis that decrease the processing of proNGF to mature NGF in AD.

PMID- 11520182
TI  - Normal CNS myelination in transgenic mice overexpressing MHC class I H-2L(d) in
      oligodendrocytes.
AB  - In demyelinating diseases, such as multiple sclerosis, an upregulation of MHC
      class I expression is thought to contribute to oligodendrocyte/myelin damage. In
      order to investigate potential physiological consequences of upregulated MHC
      class I expression in oligodendrocytes, we generated transgenic mice that
      overexpress H-2L(d) under the control of the proteolipid protein (PLP) promoter
      (PLP-L(d) mice). We focused our studies on the MHC class I molecule H-2L(d),
      because of its unique intracellular transport characteristics. In the CNS of PLP
      L(d) mice, H-2L(d) was expressed by oligodendrocytes. Furthermore, H-2L(d)
      protein was transported to and expressed on the surface of oligodendrocytes. Most
      importantly, this upregulation of MHC class I expression in the CNS of PLP-L(d)
      mice did not by itself result in a de- or dysmyelinating phenotype. These
      transgenic mice are likely to provide a unique and novel tool for the analysis of
      potential roles of MHC class I-mediated mechanisms in demyelinating pathologies.

PMID- 11520185
TI  - Pathophysiology of neonatal resuscitation: application in a global context.
AB  - Despite the adoption of evidence-based guidelines for neonatal resuscitation,
      formulated with international consensus, the process of resuscitating a newly
      born infant remains a uniquely local activity. Variations in the physical
      environment, cultural and medical beliefs, and available resources mediate
      significant difference in practices worldwide. Yet, the universal nature of the
      physiology surrounding birth, and its disturbances, provides a common basis for
      reference. Recognition of the importance of assistance available at the moment of
      birth, management of the thermal environment, and establishment of adequate
      ventilation is nearly universal. Differences in specific practices arise from
      local differences in the risks and challenges to perinatal health, which, in
      turn, stem from the environment or the available resources. Valuable information
      can be learned through comparison and evaluation of different techniques. In such
      a way, the evidence base for neonatal resuscitation can be strengthened and
      infants around the world can share in the benefits realized.

PMID- 11520183
TI  - Altered nociceptive response in mice deficient in the alpha(1B) subunit of the
      voltage-dependent calcium channel.
AB  - Calcium influx through N-type calcium channels mediates synaptic transmission at
      numerous central synapses and transduces nociceptive information in the spinal
      dorsal horn. However, the precise role of N-type calcium channels in pain
      perception is not fully elucidated. To address this issue, we generated and
      analyzed knockout mice for alpha(1B,) the pore-forming subunit of the N-type
      calcium channel. Homozygous mutants are viable, fertile, and show normal motor
      coordination. In small-diameter dorsal root ganglion neurons from mutants the
      density of calcium channel currents is significantly reduced, which can be
      accounted for by the abolition of N-type currents. We performed several pain
      related behavioral tests using the mutant mice. alpha(1B)-Deficient mice show
      reduced response to mechanical stimuli in the von Frey test and increased tail
      flick latency in response to radiant heat, indicating altered spinal reflexes.
      However, pain response in the hot plate test is normal. In the formalin paw test,
      the mutant mice exhibit significantly attenuated response in Phase 2, but normal
      pain behaviors in Phase 1. The response to visceral inflammatory pain caused by
      acetic acid is also reduced in alpha(1B) knockout mice. These results suggest
      that the alpha(1B) subunit of N-type calcium channel plays a major role in pain
      perception by acting at the spinal level, but not at the supraspinal level.

PMID- 11520186
TI  - The importance of ventilation to effective resuscitation in the term and preterm
      infant.
AB  - Although resuscitation at birth often has a successful outcome, there is very
      little data available on the optimal method. Face mask/bag resuscitation is
      relatively ineffective, rarely producing adequate alveolar ventilation before
      lung expansion has occurred, probably depending on the Head's Paradoxical Reflex
      to stimulate inspiratory efforts The T-piece/face mask technique is easier to use
      and more effective as the inflation pressure can be maintained for longer.
      Standard T-piece/endotracheal tube resuscitation produces inflation volumes of
      less than half of those generated by spontaneously breathing infants, and the
      functional residual capacity is not formed for several breaths. This can be
      overcome by maintaining the first inflation for 3 s. More studies are urgently
      required in very preterm infants as these are particularly vulnerable to
      volutrauma immediately after delivery.

PMID- 11520187
TI  - Handling the meconium-stained infant.
AB  - Clinicians who care for infants in the delivery room or afterward must frequently
      manage many born through meconium-stained amniotic fluid (MSAF). Approximately 5%
      of infants born through MSAF develop meconium aspiration syndrome (MAS). This
      disorder can be severe in nature, with half or more of the affected children
      needing mechanical ventilation. It is frequently associated with pulmonary air
      leaks and the presence of persistent pulmonary hypertension. MAS is the most
      common disorder for which babies may be treated with extracorporeal life support.
      Various possibilities for preventing MAS exist during labor, parturition, and the
      first minutes of life. Proposed antenatal therapies include amnioinfusion;
      intrapartum maneuvers include oropharyngeal suctioning prior to delivery of the
      babies shoulders; the postnatal intervention of intubation for intratracheal
      suctioning should be reserved for the non-vigorous meconium-stained infant.

PMID- 11520188
TI  - Resuscitation of newborn infants with room air or oxygen.
AB  - Oxygen is a toxic agent and a critical approach regarding its use during
      resuscitation at birth is developing. Animal data indicate that room air is
      efficient for newborn resuscitation. Three clinical studies have established that
      normal ventilation is delayed after oxygen resuscitation. Oxidative stress is
      augmented for several weeks in infants exposed to oxygen at birth -- the long
      term implications of these observations remain unclear. There are limited data
      regarding the use of room air during complicated resuscitations, i.e. in meconium
      aspiration, the severely asphyxiated infant and in the preterm infant. Thus, it
      is necessary to continue ongoing rigorous examination of the long-accepted
      practice of oxygen administration during neonatal resuscitation.

PMID- 11520189
TI  - Is temperature important in delivery room resuscitation?
AB  - The possibility that temperature may affect the outcome of resuscitation from
      severe perinatal asphyxia has been a long-standing focus of research.
      Experimentally it is now well established that even small changes in temperature
      during severe hypoxia-ischemia critically modulate outcome. Clinical and
      experimental studies have now shown that hypoxic-ischemic injury continues to
      evolve after resuscitation. Experimentally, prolonged mild to moderate
      hypothermia can dramatically reduce this delayed injury, while mild hyperthermia
      over the same period worsens injury. Indeed there are data indicating that
      moderate post-ischemic hyperthermia can be deleterious as late as 24 h after
      reperfusion. Hypothermia has significant potential adverse effects, and at
      present its clinical use is restricted to large randomized controlled trials. The
      present paper reviews evidence suggesting that both primary prevention of
      maternal pyrexia during labour, and secondary prevention of hyperthermia after
      neonatal resuscitation, have the potential to significantly reduce the
      consequences of perinatal hypoxia-ischemia.

PMID- 11520190
TI  - Medications during resuscitation -- what is the evidence?
AB  - Medication use during neonatal resuscitation is uncommon. The infrequent use of
      resuscitation medications has impeded rigorous investigations to determine the
      most effective agents and/or dosing regimens. The medications most commonly used
      during delivery room resuscitation include epinephrine, sodium bicarbonate,
      naloxone hydrochloride and volume expanders. The available evidence for each of
      these medications is reviewed in this article.

PMID- 11520191
TI  - Ethical considerations in neonatal resuscitation: clinical and research issues.
AB  - The recent publication of guidelines for ethical decision making for
      resuscitation of infants has highlighted the problems inherent in using the
      currently available data to define those situations in which resuscitation should
      be or might be withheld or withdrawn. Prior selection criteria for resuscitation,
      criteria for inclusion into the study group, incomplete resuscitation,
      gestational age determination, intrauterine growth restriction, subjective
      assessment of 'poor' outcome, and other factors make setting specific parameters
      for acting or not acting difficult, if not dangerous, and possibly impossible.
      Research in neonatal resuscitation poses some potential ethical obstacles, but
      national and international regulations and guidelines are available to assist
      investigators in study design.

PMID- 11520192
TI  - Post-resuscitative management of the asphyxiated term and preterm infant.
AB  - Up until the recent past, the treatment for perinatal asphyxia included only
      supportive measures. Babies were resuscitated and then observed for signs of
      multi-organ system dysfunction. Apart from standard supportive management, a new
      arsenal of potential neuroprotective strategies have emerged over the past years,
      in order to decrease the severity of brain injury following asphyxia. Today,
      several neuroprotective therapies are being evaluated in human infants.

PMID- 11520193
TI  - Specific inhibition of a family 1A dihydroorotate dehydrogenase by benzoate
      pyrimidine analogues.
AB  - Dihydroorotate dehydrogenases (DHODs) catalyze the conversion of dihydroorotate
      to orotate in de novo pyrimidine biosynthesis. We have found that 3,4
      dihydroxybenzoate and 3,5-dihydroxybenzoate are competitive inhibitors vs
      dihydroorotate with the prototypical family 1A DHOD from Lactococcus lactis. The
      dissociation constants of these compounds, determined by spectral titrations,
      were similar to the dissociation constant of orotate, the enzymatic reaction
      product, suggesting that hydroxybenzoates could be developed into useful drugs
      for treating infections by certain protozoan parasites.

PMID- 11520194
TI  - Structure-based design: potent inhibitors of human brain memapsin 2 (beta
      secretase).
AB  - Memapsin 2 (beta-secretase) is one of two proteases that cleave the beta-amyloid
      precursor protein (APP) to produce the 40-42 residue amyloid-beta peptide (Abeta)
      in the human brain, a key event in the progression of Alzheimer's disease. On the
      basis of the X-ray crystal structure of our lead inhibitor (2, OM99-2 with eight
      residues) bound to memapsin, we have reduced the molecular weight and designed
      potent memapsin inhibitors. Structure-based design and preliminary structure
      activity studies have been presented.

PMID- 11520195
TI  - Utilization of a peptide lead for the discovery of a novel PTP1B-binding motif.
AB  - Examination of the PTP1B inhibitory potency of an extensive series of
      phosphotyrosyl (pTyr) mimetics (Xxx) expressed in the EGFr-derived hexapeptide
      platform Ac-Asp-Ala-Asp-Xxx-Leu-amide previously led to the finding of high
      inhibitory potency when Xxx = 4-(phosphonodifluoromethyl)phenylalanyl (F2Pmp)
      (K(i) = 0.2 microM) and when Xxx = 3-carboxy-4-carboxymethyloxyphenylalanyl (K(i)
      = 3.6 microM). In the first instance, further work led from the F2Pmp-containing
      peptide to monomeric inhibitor, 6-(phosphonodifluoromethyl)-2-naphthoic acid
      (K(i) = 22 microM), and to the pseudo-dipeptide mimetic, N-[6
      (phosphonodifluoromethyl)-2-naphthoyl]-glutamic acid (K(i) = 12 microM). In the
      current study, a similar approach was applied to the 3-carboxy-4
      carboxymethyloxyphenylalanyl-containing peptide, which led to the preparation of
      monomeric 5-carboxy-6-carboxymethyloxy-2-naphthoic acid (K(i) = 900 microM).
      However, contrary to expectations based on the aforementioned F2Pmp work,
      incorporation of this putative pTyr mimetic into the pseudo-dipeptide, N-[5
      carboxy-6-carboxymethyloxy-2-naphthoyl]-glutamic acid, resulted in a substantial
      loss of binding affinity. A reevaluation of binding orientation for 5-carboxy-6
      carboxymethyloxy-2-naphthoic acid was therefore undertaken, which indicated a 180
      degrees reversal of the binding orientation within the PTP1B catalytic site. In
      the new orientation, the naphthyl 2-carboxyl group, and not the o-carboxy
      carboxymethyloxy groups, mimics a phosphoryl group. Indeed, when 5-carboxy-2
      naphthoic acid itself was examined at neutral pH for inhibitory potency, it was
      found to have K(i) = 31 +/- 7 microM, which is lower than parent 5-carboxy-6
      carboxymethyloxy-2-naphthoic acid. In this fashion, 5-carboxy-2-naphthoic acid
      (or more appropriately, 6-carboxy-1-naphthoic acid) has been identified as a
      novel PTP1B binding motif.

PMID- 11520196
TI  - Synthesis and characterization of non-steroidal ligands for the glucocorticoid
      receptor: selective quinoline derivatives with prednisolone-equivalent functional
      activity.
AB  - A novel class of functional ligands for the human glucocorticoid receptor is
      described. Substituents in the C-10 position of the tetracyclic core are
      essential for glucocorticoid receptor (GR) selectivity versus other steroid
      receptors. The C-5 position is derivatized with meta-substituted aromatic groups,
      resulting in analogues with a high affinity for GR (K(i) = 2.4-9.3 nM) and
      functional activity comparable to prednisolone in reporter gene assays of
      glucocorticoid-mediated gene transcription. The biological activity of these
      novel quinolines was also prednisolone-equivalent in whole cell assays of
      glucocorticoid function, and compound 13 was similar to prednisolone (po ED(50) =
      2.8 mpk for 13 vs ED(50) = 1.2 mpk for prednisolone) in a rodent model of asthma
      (sephadex-induced eosinophil influx).

PMID- 11520197
TI  - Synthesis, molecular modeling, and structure-activity relationship of
      benzophenone-based CAAX-peptidomimetic farnesyltransferase inhibitors.
AB  - Because of the involvement of farnesylated proteins in oncogenesis, inhibition of
      the protein-modifying enzyme farnesyltransferase is considered a major emerging
      strategy in cancer therapy. Here, we describe the structure-activity relationship
      of a novel class of CAAX-peptidomimetic farnesyltransferase inhibitors based on
      the benzophenone scaffold. 4'-Methyl, 4'-chloro, 4'-bromo, and 4'
      nitrophenylacetic acid as substituents at the 2-amino group of the benzophenone
      core structure yield farnesyltransferase inhibitors active in the nanomolar
      range. Using diphenylacetic acid in this position further improves activity. SEAL
      superimposition of inhibitor 12a to the enzyme-bound conformation of a CAAX
      peptide shows a markedly good resemblance of the molecular properties of the
      peptide. FlexX docking of 12a confirms the good fit of the molecule into the
      peptide binding site of farnesyltransferase. The novel benzophenone-based AAX
      peptidomimetic substructure described here will be useful for the design of some
      novel types of farnesyltransferase inhibitors.

PMID- 11520198
TI  - 2-N-acylaminoalkylindoles: design and quantitative structure-activity
      relationship studies leading to MT2-selective melatonin antagonists.
AB  - Several indole analogues of melatonin (MLT) were obtained by moving the MLT side
      chain from C(3) to C(2) of the indole ring. Binding and in vitro functional
      assays were performed on cloned human MT1 and MT2 receptors, stably transfected
      in NIH3T3 cells. Quantitative structure-activity relationship studies showed that
      4-methoxy-2-(N-acylaminomethyl)indoles, with a benzyl group in position 1, were
      selective MT2 antagonists and, in particular, N-[(1-p-chlorobenzyl-4-methoxy-1H
      indol-2-yl)methyl]propanamide (12) behaved as a pure antagonist at MT1 and MT2
      receptors, with a 148-fold selectivity for MT2. We present a topographical model
      that suggests a lipophilic group, located out of the plane of the indole ring of
      MLT, as the key feature of the MT2 selective antagonists.

PMID- 11520199
TI  - Discovery of potent antagonists of leukocyte function-associated antigen
      1/intercellular adhesion molecule-1 interaction. 3. Amide (C-ring) structure
      activity relationship and improvement of overall properties of arylthio
      cinnamides.
AB  - The interaction of LFA-1 and ICAM-1 plays an important role in the cell adhesion
      process. On the basis of previously reported SAR and structural information on
      the binding of our p-arylthiocinnamide series to LFA-1, we have identified the
      cyclic amide (C-ring) as a site for modification. Improvement in potency and,
      more importantly, in the physical properties and pharmacokinetic profiles of the
      leading compounds resulted from this modification. One of the best compounds
      (11f) is also shown to reduce myocardial infarct size in rat.

PMID- 11520200
TI  - Design and synthesis of 4,5-diphenyl-4-isoxazolines: novel inhibitors of
      cyclooxygenase-2 with analgesic and antiinflammatory activity.
AB  - 4,5-Diphenyl-4-isoxazolines (13a-k) possessing a variety of substituents (H, F,
      MeS, MeSO2) at the para position of one of the phenyl rings were synthesized for
      evaluation as analgesic and selective cyclooxygenase-2 (COX-2) inhibitory
      antiinflammatory (AI) agents. Although the 4,5-phenyl-4-isoxazolines (13a-d,f),
      which do not have a C-3 Me substituent, exhibited potent analgesic and AI
      activities, those compounds evaluated (13a, 13b, 13h, and 13k) were not selective
      inhibitors of COX-2. In contrast, 2,3-dimethyl-5-(4-methylsulfonylphenyl)-4
      phenyl-4-isoxazoline (13j) exhibited excellent analgesic and AI activities, and
      it was a potent and selective COX-2 inhibitor (COX-1, IC(50) = 258 microM; COX-2,
      IC(50) = 0.004 microM). A related compound 13k having a F substituent at the para
      position of the 4-phenyl ring was also a selective (SI = 3162) but less potent
      (IC(50) = 0.0316 microM) inhibitor of COX-2 than 13j. A molecular modeling
      (docking study) for 13j showed that the S atom of the MeSO2 substituent is
      positioned about 6.46 A inside the entrance to the COX-2 secondary pocket
      (Val(523)) and that a C-3 Me (13j, 13k) central isoxazoline ring substituent is
      crucial to selective inhibition of COX-2 for this class of compounds.

PMID- 11520201
TI  - X-Ray crystal structures of Candida albicans dihydrofolate reductase: high
      resolution ternary complexes in which the dihydronicotinamide moiety of NADPH is
      displaced by an inhibitor.
AB  - X-ray crystallographic analysis of 5-(4'-substituted phenyl)sulfanyl-2,4
      diaminoquinazoline inhibitors in ternary complex with Candida albicans
      dihydrofolate reductase (DHFR) and NADPH revealed two distinct modes of binding.
      The two compounds with small 4'-substituents (H and CH3) were found to bind with
      the phenyl group oriented in the plane of the quinazoline ring system and
      positioned adjacent to the C-helix. In contrast, the more selective inhibitors
      with larger 4'-substituents (tert-butyl and N-morpholino) were bound to the
      enzyme with the phenyl group perpendicular to the quinazoline ring and positioned
      in the region of the active site that typically binds the dihydronicotinamide
      moiety of NADPH. The cofactor appeared bound to DHFR but with the disordered
      dihydronicotinamide swung away from the protein surface and into solution. This
      unusual inhibitor binding mode may play an important role in the high DHFR
      selectivity of these compounds and also may provide new ideas for inhibitor
      design.

PMID- 11520203
TI  - Novel hypotensive agents from Verbesina caracasana. 8. Synthesis and pharmacology
      of (3,4-dimethoxycinnamoyl)-N(1)-agmatine and synthetic analogues.
AB  - The more polar metabolites from the Venezuelan plant Verbesina caracasana, i.e.,
      N(3)-prenylagmatine, (3,4-dimethoxycinnamoyl)-N(1)-agmatine, agmatine, and
      galegine (prenylguanidine), previously reported (Delle Monache, G.; et al.
      BioMed. Chem. Lett. 1999, 9, 3249-3254), have been synthesized following a
      biosynthetic strategy. The pharmacologic profiles of various synthetic analogues
      of (3,4-dimethoxycinnamoyl)-N(1)-agmatine (G5) were also analyzed, to shed some
      light on the structure-activity relationship of these compounds. Derivatives with
      the (E)-configuration and/or with a p-methoxybenzoyl moiety were found to be
      responsible for higher hypotensive effects, which were associated with a slight
      and, in some cases, not dose-related increase of cardiac inotropism, with
      variable and not significant chronotopic responses, and, only at higher doses,
      with effects of respiratory depression. Either an increase (to six) or a decrease
      (to two) of the number of methylene groups in the alkyl chain of (E)-G5 did not
      change blood pressure responses, while slightly increasing the positive inotropic
      ones. At pharmacological doses, all the studied compounds showed hypotensive and
      slight positive inotropic effects without relevant chronotropic and respiratory
      actions.

PMID- 11520202
TI  - Design and biological activity of (S)-4-(5-([1-(3-chlorobenzyl)-2-oxopyrrolidin-3
      ylamino]methyl)imidazol-1-ylmethyl)benzonitrile, a 3-aminopyrrolidinone
      farnesyltransferase inhibitor with excellent cell potency.
AB  - The synthesis, structure-activity relationships, and biological properties of a
      novel series of imidazole-containing inhibitors of farnesyltransferase are
      described. Starting from a 3-aminopyrrolidinone core, a systematic series of
      modifications provided 5h, a non-thiol, non-peptide farnesyltransferase inhibitor
      with excellent bioavailability in dogs. Compound 5h was found to have an
      unusually favorable ratio of cell potency to intrinsic potency, compared with
      other known FTIs. It exhibited excellent potency against a range of tumor cell
      lines in vitro and showed full efficacy in the K-rasB transgenic mouse model.

PMID- 11520204
TI  - Synthesis and in vitro antitumor activity of oligonucleotide-tethered and related
      platinum complexes.
AB  - Three classes of hydroxy-tethered platinum(II) complexes have been synthesized
      from K(2)PtCl(4) and appropriate amino alcohols. A sequence of selective
      oxidation and hydrolysis has been developed to prepare hydroxy-tethered
      platinum(IV) complexes. A novel procedure for the synthesis of
      amminetrichloroplatinate(II) anion has been generated and used to synthesize a
      number of monohydroxy-tethered nonchelating platinum complexes. These tethered
      platinum complexes, including hydroxy-tethered, phosphoramidite-tethered, and
      monodeoxyribonucleotide-tethered platinum(II) and -(IV) complexes, have been
      examined in vitro for antitumor activity in both leukemia and ovarian cancer cell
      lines. Activity of some of these complexes was similar to cis-platin, and most of
      them showed much better potency than carboplatin. We observed an interesting
      structure-activity correlation for platinum(II) complexes for both PA-1 and SK-OV
      3 ovarian cancer cell lines. However, platinum(IV) complexes showed much more
      diversified response among cancer cell lines studied. We observed enhanced
      selectivity among different cancer cell lines for some agents. The most promising
      is the monodeoxyribonucleotide-tethered platinum(IV) complex, which is the first
      analogue of the conjugates between a platinum fragment and
      monodeoxyribonucleotides, showing antitumor activity and selectivity among the
      cell lines. Finally, the p53 status of the cells appears to contribute to the
      effectiveness of these agents in that cells harboring wild-type p53 appear to be
      more sensitive to these agents.

PMID- 11520205
TI  - 5'-O-alkyl ethers of N,2-substituted adenosine derivatives: partial agonists for
      the adenosine A1 and A3 receptors.
AB  - New N,5'-di- and N,2,5'-trisubstituted adenosine derivatives were synthesized in
      good overall yields. Appropriate 5-O-alkyl-substituted ribose moieties were
      coupled to 6-chloropurine or 2,6-dichloropurine via Vorbruggen's glycosylation
      method. Subsequent amination and deprotection of the intermediates yielded
      compounds 18-35. Binding affinities were determined for rat adenosine A1 and A2A
      receptors and the human A3 receptor. The ability of compounds 18-35 to inhibit
      forskolin-induced (10 microM) cyclic AMP (cAMP) production and their ability to
      stimulate guanosine 5'-O-(3-[35S]thio)triphosphate ([35S]GTPgammaS) binding, via
      either the adenosine A1 receptor or the adenosine A3 receptor, were assessed. N
      Cyclopentyl-substituted adenosine derivatives displayed affinities in the low
      nanomolar range for the adenosine A1 receptor, whereas N-(3-iodobenzyl)
      substituted derivatives had high affinity for the adenosine A3 receptor. Compound
      22 had the highest affinity for the adenosine A1 receptor (K(i) value of 16 nM),
      and compounds 20 and 26 had the highest affinities for the adenosine A3 receptor
      (K(i) values of 4 and 3 nM, respectively). A chlorine substituent at the 2
      position either did not affect or slightly increased the adenosine A1 receptor
      affinity, whereas the A3 receptor affinity was affected differently, depending on
      the N-substituent. Furthermore, the introduction of chlorine slightly increased
      the A3/A1 selectivity ratio. At the 5'-position, an O-methyl substituent induced
      the highest adenosine A1 receptor affinity, whereas an O-ethyl substituent did so
      for the A3 receptor. All compounds showed partial agonistic effects in both the
      cAMP and [35S]GTPgammaS assays, although more marked in the latter assay. In
      general, the 2-chloro derivatives seemed to have lower intrinsic activities
      compared to the 2-H-substituted compounds on both the adenosine A1 and the
      adenosine A3 receptors. The compounds with an N-(3-iodobenzyl) substituent
      displayed the lowest intrinsic activities. Finally, all compounds also showed
      partially antagonistic behavior in the [35S]GTPgammaS assay.

PMID- 11520206
TI  - QSAR study on the contribution of log P and E(s) to the in vitro antiprotozoal
      activity of glutathione derivatives.
AB  - A series of N-S-blocked glutathione monoester and diester derivatives based on N
      benzyloxycarbonyl-S-(2,4-dinitrophenyl)glutathione were evaluated for activity
      against the pathogenic parasites Trypanosoma brucei brucei, Trypanosoma cruzi,
      and Leishmania donovani in vitro.Only monoesters 7-9 with a log P value of >2.7
      were active inhibitors of T.b. brucei bloodstream form trypomastigotes. Diester
      compounds 10-15 and 17-27 in most cases were better inhibitors of T.b. brucei
      than monoester compounds, and some displayed high activity against T. cruzi 14
      and L. donovani 17, 19, 29. Compounds 14, 24, and 25 were the most active
      compounds identified against T.b. brucei having ED(50) values of <0.4 microM.
      Analysis of the inhibition data (ED(50)) vs calculated log P and E(s) values
      provided evidence to support membrane penetration and steric factors as the key
      component in the activity of these compounds. The optimum values for log P and
      E(s) determined were 5.8 and -0.70, respectively. A QSAR equation relating
      log(1/ED(50)) vs log P and E(s) was determined and interpreted within the
      proposed mechanism of activity for these compounds.

PMID- 11520207
TI  - Synthesis and biological activity of D- and L-chiro-inositol 2,3,4,5
      tetrakisphosphate: design of a novel and potent inhibitor of Ins(3,4,5,6)P4 1
      kinase/Ins(1,3,4)P3 5/6-kinase.
AB  - The synthesis of a novel and potent Ins(3,4,5,6)P4 1-kinase/Ins(1,3,4)P3 5/6
      kinase inhibitor and its enantiomer is described. D-chiro-Inositol 2,3,4,5
      tetrakisphosphate [D-chiro-Ins(2,3,4,5)P4, 3, Figure 1] and L-chiro-inositol
      2,3,4,5-tetrakisphosphate [L-chiro-Ins(2,3,4,5)P4, ent-3] were synthesized from D
      1,6-di-O-benzyl-chiro-inositol and L-1,6-di-O-benzyl-chiro-inositol,
      respectively. We examined inhibition of the multifunctional Ins(3,4,5,6)P4 1
      kinase/Ins(1,3,4)P3 5/6-kinase from bovine aorta by 3 and ent-3. Compound 3 was a
      potent inhibitor with an IC(50) of 1.5 microM, and ent-3 was more than 20-fold
      less active. The results are compared to those for other inhibitory inositol
      polyphosphates with structure-activity relationship discussion. Compound 3 is a
      useful lead for development of further inhibitors of this important enzyme, and
      ent-3 should find applications in the newly emerging Ins(1,4,5,6)P4 signaling
      pathway.

PMID- 11520208
TI  - Identification of potent non-peptide somatostatin antagonists with sst(3)
      selectivity.
AB  - Using a solution-phase parallel synthesis strategy, a series of non-peptide
      somatostatin analogues were prepared, and their binding affinities to the five
      human somatostatin receptor subtypes (sst(1-5)) were determined. Imidazolyl
      derivatives 2 were found to bind with moderate affinity but with high selectivity
      to the sst(3) receptor subtype. Further modifications of these structures led to
      a more potent class of ligands, the tetrahydro-beta-carboline derivatives 4.
      Among these, compounds 4k (BN81644) and 4n (BN81674) bind selectively and with
      high affinity to the sst(3) receptor subtype (K(i) = 0.64 and 0.92 nM,
      respectively). Furthermore, 4k and 4n reverse the inhibition of cyclic AMP
      accumulation induced by 1 nM somatostatin via sst(3) receptors, with IC(50) = 2.7
      and 0.84 nM, respectively. The most potent compound 4n was shown to be a
      competitive antagonist of human sst(3) receptors by increasing the EC(50) of SRIF
      14-mediated inhibition of cAMP accumulation with a K(B) of 2.8 nM (where K(B) is
      the concentration of antagonist that shifts the agonist dose-response 2-fold).
      These new derivatives are, to our knowledge, the first potent and highly
      selective non-peptide human sst(3) antagonists known and, as such, are useful
      tools for investigating the physiological role of sst(3) receptors.

PMID- 11520209
TI  - Novel azo derivatives as prodrugs of 5-aminosalicylic acid and amino derivatives
      with potent platelet activating factor antagonist activity.
AB  - This paper describes the synthesis of a series of azo compounds able to deliver 5
      aminosalicylic acid (5-ASA) and a potent platelet activating factor (PAF)
      antagonist in a colon-specific manner for the purpose of treating ulcerative
      colitis. We found it possible to add an amino group on the aromatic moiety of our
      reported 1-[(1-acyl-4-piperidyl)methyl]-1H-2-methylimidazo[4,5-c]pyridine
      derivatives or on British Biotech compounds BB-882 and BB-823 maintaining a high
      level of activity as PAF antagonist. A selected compound UR-12715 (49c) showed an
      IC(50) of 8 nM in the in vitro PAF-induced aggregation assay, and an ID(50) of 29
      microg/kg in the in vivo PAF-induced hypotension test in normotensive rats.
      Through attachment of 49c to the 5-ASA via azo functionality we obtained UR-12746
      (70). Pharmacokinetics experiments with [14C]-70 allow us to reach the following
      conclusions, critical in the design of these new prodrugs of 5-ASA. Neither the
      whole molecule 70 nor the carrier 49c were absorbed after oral administration of
      [14C]-70 in rat as was demonstrated by the absence of plasma levels of
      radioactivity and the high recovery of it in feces. Effective cleavage of azo
      bond (84%) by microflora in the colon is achieved. These facts ensure high
      topical concentrations of 5-ASA and 49c in the colon. Additionally, 70 exhibited
      a potent anticolitic effect in the trinitrobenzenesulfonic acid-induced colitis
      model in the rat. This profile suggests that UR-12746 (70) provides an attractive
      new approach to the treatment of ulcerative colitis.

PMID- 11520210
TI  - New 3'-azido-3'-deoxythymidin-5'-yl O-(4-hydroxyalkyl or -alkenyl or 
      alkylepoxide) carbonate prodrugs: synthesis and anti-HIV evaluation.
AB  - New 5'-O-carbonate prodrugs of zidovudine (AZT) have been synthesized in order to
      enhance its uptake by HIV-1 infected cells, to improve its anti-HIV potency, and
      to optimize the intramolecular cyclic rearrangement process related to the 5'-O
      (4-hydroxybutyl) carbonate moiety. Evidence of this prodrug rearrangement was
      confirmed by comparison of the serum half-lives of the 3'-azido-3'-deoxythymidin
      5'-yl O-(4-hydroxyalkyl or -alkenyl or -alkylepoxide) carbonate prodrugs with our
      thermodynamic predictions. Interestingly, these 5'-O-carbonate prodrug series
      show increased anti-HIV potencies in conjunction with, or without, reduced
      cytotoxicity as compared to AZT that lead to a gain in selectivity indexes. The
      cytotoxicity of AZT could be reduced with these 5'-O-carbonate prodrug series by
      delaying the 5'-O-glucuronidation of AZT, which is one of the major limitations
      of AZT.

PMID- 11520211
TI  - Design, synthesis and pharmacological characterization of a potent radioiodinated
      and photoactivatable peptidic oxytocin antagonist.
AB  - Using a segment strategy, we have synthesized four iodinated photoactivatable
      cyclic peptidic ligands of oxytocin, bearing a beta-mercapto-betabeta
      cyclopentamethylene propionic group (Pmp) on their N-terminus. All the syntheses
      were RP-HPLC monitored, and the compounds were HPLC purified. They were
      characterized by 1H NMR, MALDI-TOF, or FAB mass spectrometries. The affinities of
      Pmp-Tyr(Me)-Ile-Thr-Asn-Cys-Gly-Orn-Phe(3I,4N3)-NH2 (20), Pmp-Tyr-Ile-Thr-Asn-Cys
      Gly-Orn-Phe(3I,4N3)-NH2 (21), Pmp-Tyr(Me)-Ile-Thr-Asn-Cys-Pro-Orn-Phe(3I,4N3)-NH2
      (22), and Pmp-Tyr-Ile-Thr-Asn-Cys-Pro-Orn-Phe(3I,4N3)-NH2 (23) were evaluated as
      inhibition constants (K(i), in nM) for the human oxytocin receptor expressed in
      Chinese hamster ovary cells by displacement of a radioiodinated disulfide
      cyclized antagonist (Elands et al. Eur. J. Pharmacol. 1987, 147, 197-207). The
      most potent of them, compound 22, was synthesized by another method in order to
      allow its radiolabeling by 125I. Its dissociation constant (K(d)) for the human
      oxytocin receptor, directly measured in saturation studies, was 0.25 +/- 0.04 nM,
      and its antagonist properties were determined by inactivation of phospholipase C,
      thus obtaining an inactivation constant (K(inact)) of 0.18 +/- 0.02 nM, evaluated
      by inositol phosphate accumulation. This compound is a very good tool for the
      mapping of peptidic antagonist binding sites in the human oxytocin receptor.

PMID- 11520212
TI  - S(+)-4-(1-Phenylethylamino)quinazolines as inhibitors of human immunoglobulin E
      synthesis: potency is dictated by stereochemistry and atomic point charges at N
      1.
AB  - Since the pathogenesis of allergic diseases is associated with elevated levels of
      immunoglobulin E (IgE), we developed a high throughput reporter gene assay in a
      human B-cell line to screen for low molecular weight IgE inhibitory compounds.
      Monitoring the IL-4 driven IgE-germline promoter activity (IgE-GLP), we
      discovered 4-(1-phenylethylamino)qinazolines as potent inhibitors of IgE-germline
      gene expression. Testing of the individual enantiomers (1, 2) revealed that only
      the S(+) enantiomer 1 was active. A cell viability assay done in the same cell
      line in parallel discriminated the dose-dependent inhibition from a general
      antiproliferative effect. The observed correlation of the inhibitory potencies
      found in the reporter gene assay with those measured by IgE-ELISA in primary
      human splenocytes provided evidence that the blockade of IgE synthesis is the
      direct consequence of IgE-germline gene inhibition, thereby validating the
      reporter gene assay. Parallel synthesis in solution rapidly provided a series of
      analogues of compound 1 with modifications in the phenethylamine side chain and
      the quinazoline core for SAR studies. Increasing the lipophilicity of the
      arylalkylamine moiety yielded S(+)-4-(1-(2-naphthyl)ethylamino)quinazoline (6) as
      the most potent inhibitor (IC(50) of 14 nM) while the R(-) enantiomer was again
      found to be inactive. Within the set of S enantiomers, quantum mechanical
      calculations revealed that the IgE inhibitory activity can be quantitatively
      described by the charge at N-1 of the heterocyclic core and to a lesser extent by
      the molar refractivity. These results demonstrate the importance of electron
      deficient fused 4-aminopyrimidines and lipophilic side chains for biological
      activity. The strong preference for the S configuration of the phenethylamine
      side chain is remarkable insofar as biological activity for fused 4-(1
      phenylethylamino)pyrimidines has been published for the R enantiomers only (EGFR
      tyrosine kinase inhibition).

PMID- 11520213
TI  - Design and synthesis of celecoxib and rofecoxib analogues as selective
      cyclooxygenase-2 (COX-2) inhibitors: replacement of sulfonamide and
      methylsulfonyl pharmacophores by an azido bioisostere.
AB  - Celecoxib (13) and rofecoxib (17) analogues, in which the respective SO2NH2 and
      SO2Me hydrogen-bonding pharmacophores were replaced by a dipolar azido
      bioisosteric substituent, were investigated. Molecular modeling (docking) studies
      showed that the azido substituent of these two analogues (13, 17) was inserted
      deep into the secondary pocket of the human COX-2 binding site where it undergoes
      electrostatic interaction with Arg(513). The azido analogue of rofecoxib (17),
      the most potent and selective inhibitor of COX-2 (COX-1 IC(50) = 159.7 microM;
      COX-2 IC(50) = 0.196 microM; COX-2 selectivity index = 812), exhibited good oral
      antiinflammatory and analgesic activities.

PMID- 11520214
TI  - New indole alkaloids from the bark of Nauclea orientalis.
AB  - Four new alkaloids, nauclealines A (1) and B (2) and naucleosides A (3) and B
      (4), together with six known compounds, strictosamide (5), vincosamide (6),
      pumiloside (7), kelampayoside A, sitosterol, and sitosteryl beta-D-glucoside,
      were isolated from the bark of Nauclea orientalis. The structures of 1-4 were
      elucidated using 1D and 2D NMR spectral methods, including COSY, DEPT, HMQC,
      (13)C-(1)H HMBC, and (15)N-(1)H HMBC.

PMID- 11520215
TI  - Dicerandrols, new antibiotic and cytotoxic dimers produced by the fungus
      Phomopsis longicolla isolated from an endangered mint.
AB  - Bioassay-guided fractionation of the organic extract from a culture of Phomopsis
      longicolla, an endophytic fungus of the endangered mint Dicerandra frutescens,
      led to the isolation of dicerandrols A, B, and C. Extensive NMR and HRFABMS
      experiments were used to identify these new yellow antibiotic and cytotoxic
      compounds as 2,2'-dimeric tetrahydroxanthones.

PMID- 11520216
TI  - Ellagitannins and hexahydroxydiphenoyl esters as inhibitors of vertebrate
      squalene epoxidase.
AB  - Ellagitannins isolated from various plant sources as well as newly synthesized n
      alkyl (C(1)-C(18)) esters of hexahydroxydiphenyl (HHDP) dicarboxylic acid were
      evaluated as enzyme inhibitors of recombinant rat squalene epoxidase, a rate
      limiting enzyme of cholesterol biosynthesis. Among the ellagitannins tested,
      pedunculagin (IC(50) = 2.0 microM) and eugeniin (IC(50) = 1.6 microM), both
      containing (S)-HHDP ester group(s), showed remarkable inhibition, which was more
      potent than those of previously reported substrate analogue inhibitors.
      Furthermore, ellagic acid (IC(50) = 2.0 microM), a bislactone formed by
      hydrolytic release of a HHDP group from ellagitannins, was also a good inhibitor
      of the enzyme. On the other hand, the synthetic HHDP esters with C(6) (IC(50) =
      0.93 microM) and C(8) alkyl side chains (IC(50) = 0.83 microM) showed potent
      enzyme inhibition at the submicromolar concentration range, while esters with
      shorter chain lengths (C(1)-C(4)) and a C(18) ester exhibited moderate inhibition
      (IC(50) = 8-47 microM).

PMID- 11520217
TI  - Phomoxanthones A and B, novel xanthone dimers from the endophytic fungus
      Phomopsis species.
AB  - Phomoxanthones A (1) and B (2), two novel xanthone dimers, were isolated from the
      endophytic fungus Phomopsis sp. BCC 1323. Structures of 1 and 2 were elucidated
      by spectroscopic methods. These compounds exhibited significant in vitro
      antimalarial and antitubercular activities and cytotoxicity.

PMID- 11520218
TI  - Phenolic constituents and antioxidant activity of an extract of
      Anthuriumversicolor leaves.
AB  - Fractionation of a methanolic extract of the leaves of Anthurium versicolor has
      resulted in the isolation of two main fractions, I and II. Both the extract and
      the fractions were assayed for their radical-scavenging activity by means of an
      in vitro test (bleaching of the stable 1,1-diphenyl-2-picrylhydrazyl radical) and
      showed a significant radical-scavenging effect. Subsequent chromatographic
      fractionation of the most active fraction, II, has led to the isolation and
      characterization, as major constituents, of four new flavone glycosides, acacetin
      6-C-[alpha-L-rhamnopyranosyl-(1-->3)-beta-D-glucopyranoside] (1), acacetin 6-C
      [beta-D-xylopyranosyl-(1-->6)-beta-D-glucopyranoside] (2), acacetin 6-C-[beta-D
      apiofuranosyl-(1-->3)-beta-D-glucopyranoside] (3), and acacetin 8-C-[alpha-L
      rhamnopyranosyl-(1-->3)-beta-D-glucopyranoside] (4), as well as vitexin (apigenin
      8-C-beta-D-glucopyranoside) and rosmarinic acid. The structures of 1-4 were
      determined using spectroscopic methods.

PMID- 11520219
TI  - New bromoditerpenes from the red alga Sphaerococcus coronopifolius.
AB  - The organic extract of the red alga Sphaerococcus coronopifolius, collected along
      the Atlantic coast of Morocco, was tested for biological activities and exhibited
      antibiotic and antimalarial activities. Two new bromoditerpenes have been
      isolated from S. coronopifolius, sphaerolabdadiene-3,14-diol (1) and
      bromosphaerone (2), along with the known compounds 12S-hydroxybromosphaerodiol
      (3) and sphaerococcenol A (4). Bromosphaerone and 12S-hydroxybromosphaerodiol
      showed antibacterial activity against the Gram-positive bacterium species
      Staphylococcus aureus with a minimum inhibitory concentration of 0.104 and 0.146
      microM, respectively. Sphaerococcenol A (4) was responsible for the antimalarial
      activity of the extract, against the chloroquine resistant Plasmodium falsciparum
      FCB1 strains with an IC(50) of 1 microM. Their structures have been assigned
      using 1 and 2 D NMR and HRMS.

PMID- 11520220
TI  - Cytotoxic dolabellane diterpenes from the Formosan soft coral Clavularia inflata.
AB  - Six new cytotoxic dolabellane diterpenes, (1R,12R)-dolabella-4(16),7,10-triene
      3,13-dione (1), (1R*,7R*,8S*,12R*)-dolabella-4(16),10-diene-7,8-epoxy- 3,13-dione
      (2), (1R*,10R*,11S*,12R*)-dolabella-4(16),7-diene-10,11-epoxy-3,13-dione (3),
      (1R)-dolabella-4(16),7,11(12)-triene-3,13-dione (4), (1R*,3R*)-3-hydroxydolabella
      4(16),7,11(12)-triene-3,13-dione (5), and (1R*,7R*)-7-hydroperoxydolabella
      4(16),8(17),11(12)-triene-3,13-dione (6), have been isolated from the Formosan
      soft coral Clavularia inflata. The structures of compounds 1-6 were determined by
      1D and 2D spectral analysis, and their cytotoxicity against selected cancer cells
      was measured in vitro.

PMID- 11520221
TI  - Investigation of the coupling reaction of tetraacetylsecologanin with
      oxotryptamine and its derivative.
AB  - The coupling reaction of tetraacetylsecologanin with 2,3-dihydro-2-oxotryptamine
      and its N(b)-benzyl derivative was investigated. With the benzylated amine, the
      reaction was stopped at the tetracyclic ester level, and with the unsubstituted
      amine it was immediately followed by lactamization. In both cases, the products
      were formed with high stereoselectivity at C-3, but as an epimeric pair of 7R and
      7S in a ratio of 1:3. The bulky benzyl substituent at N-4 directed the
      stereoselectivity at C-3 in favor of the S configuration. In the nonbenzylated
      compounds, the reversible coupling reaction is probably nonstereoselective, but
      in lactamization the 3R epimer is sterically favored and faster and gives the
      final lactam in this configuration. The formation of the spiro compounds may
      serve as a model reaction in the interpretation of the stereoselectivity of the
      coupling reaction of secologanin with tryptamine in the presence of strictosidine
      synthase.

PMID- 11520222
TI  - Constituents of the root bark of Severinia buxifolia collected in Hainan.
AB  - Two new tetranortriterpenoids, 7-isovaleroylcycloseverinolide (1) and 7
      isovaleroylcycloepiatalantin (2), together with 28 known compounds, were isolated
      and characterized from the root bark of Severinia buxifolia collected in Hainan.
      The structures of 1 and 2 were elucidated on the basis of spectral evidence
      including 2D NMR and X-ray techniques. The cytotoxicity of several acridone
      alkaloid isolates (3-8) was evaluated against a small tumor cell panel.

PMID- 11520223
TI  - Structure and stereochemistry of epoxyserratanes from the cuticle of
      Piceajezoensis var. jezoensis.
AB  - Three new epoxytriterpenes, 14 beta,15 beta-epoxy-21 beta-hydroxyserratan-3-one
      (1), 13 alpha,14 alpha-epoxy-21 alpha-methoxyserratan-3-one (2), and 13 alpha,14
      alpha-epoxy-3 beta-methoxyserratan-21 beta-ol (3), were isolated together with
      two known triterpenoids, 21 alpha-methoxyserrat-13-en-3-one (4) and 21 beta
      hydroxyserrat-14-en-3-one (5), from the cuticle of Picea jezoensis var.
      jezoensis. The structures of these new compounds were established on the basis of
      spectral data (NMR, MS) and single-crystal X-ray analyses (1 and 2) and partial
      synthesis (2 and 3).

PMID- 11520224
TI  - Thymol derivatives from Eupatorium fortunei.
AB  - Sixteen new thymol derivatives have been isolated from Eupatorium fortunei and
      their structures determined based on spectroscopic data. They were classified
      into three groups (i-iii) depending on the oxidation levels: (i) one oxygen
      function at the 9-position, (ii) two oxygen functions at the 8- and 9-positions,
      and (iii) three oxygen functions at the 8-, 9-, and 10-positions. The hydroxyl
      groups are acylated with tigloyl, angeloyl, acetyl, isobutyryl, 3-methyl-2
      butenoyl, or 2-methylbutyryl moieties. The compounds having chiral centers showed
      no specific rotation and exist as racemic mixtures.

PMID- 11520225
TI  - Isolation of new protein phosphatase inhibitors from two cyanobacteria species,
      Planktothrix spp.
AB  - Two new protein phosphatase inhibitors, oscillamide B (1) and C (2), were
      isolated from the cyanobacteria Planktothrix (Oscillatoria) agardhii and P.
      rubescens. The structures of the inhibitors were elucidated by analysis of
      HRFABMS, 1D and 2D NMR spectra, and chemical degradation. These inhibitors are
      ureido-containing cyclic peptides and inhibited serine/threonine protein
      phosphatases PP1 and PP2A. The inhibitory activities were closely related to the
      Arg and N-Me-Hty residues in the peptides.

PMID- 11520226
TI  - Tetillapyrone and nortetillapyrone, two unusual hydroxypyran-2-ones from the
      marine sponge Tetilla japonica.
AB  - Extraction of the marine sponge Tetilla japonica from the Bay of Thailand
      furnished tetillapyrone and nortetillapyrone, two unusual
      tetrahydrofurylhydroxypyran-2-ones, whose structures were established by NMR
      spectrometry and an X-ray analysis of tetillapyrone.

PMID- 11520227
TI  - Cytotoxic diacetylenes from the stony coral Montipora species.
AB  - Ten new (1, 4-6, 9-14) and four known (2, 3, 7, 8) diacetylenes have been
      isolated from a brine shrimp active fraction of the methanolic extract of the
      stony coral Montipora sp. The structures were determined by combined
      spectroscopic methods. The compounds exhibited significant cytotoxicity against a
      small panel of human solid tumor cell lines. Montiporyne A (15), a previously
      reported congener, was also found to induce apoptosis in human colon tumor cell.

PMID- 11520228
TI  - New jatrophane diterpenoid esters from Euphorbia turczaninowii.
AB  - Five new (1-5) and one known (6) jatrophane diterpenoid esters were isolated from
      the ethanol extract of the whole herb of Euphorbia turczaninowii. Their
      structures were established by extensive spectroscopic methods. The absolute
      stereochemistry of 3 beta,5 alpha,8 alpha,15 beta-tetraacetoxy-7 beta
      benzoyloxyjatropha-6(17),11E-dien-9,14-dione (1) was confirmed by a single
      crystal X-ray analysis coupled with the exciton chirality circular dichroism
      method. Compounds 1-6 were inactive when evaluated both in a mouse ear
      inflammation assay and for cytotoxicity against the B16 mouse melanoma cell line.

PMID- 11520229
TI  - Five new polyoxygenated cholestane bisdesmosides from the bulbs of Galtonia
      candicans.
AB  - Two new cholestane bisdesmosides (1, 2) based upon (22S)-cholest-5-ene-3 beta,16
      beta,22-triol with an acetyl group at the sugar moiety and three new ones (3-5)
      based upon (22S)-cholest-5-ene-1 beta,3 beta,16 beta,22-tetrol, along with a
      known cholestane glycoside, were isolated from the bulbs of Galtonia candicans.
      The structures of the new compounds were determined by spectroscopic analysis and
      chemical transformations.

PMID- 11520230
TI  - Dantaxusins A and B, two new taxoids from Taxus yunnanensis.
AB  - Two new taxane diterpenes, dantaxusin A [5 alpha-cinnamoyloxy-2 alpha,7 beta,13
      alpha-triacetoxy-2(3-->20)abeo-taxa-4(20),11-diene-9,10-dione (1)] and dantaxusin
      B [5 alpha-cinnamoyloxy-9 alpha-hydroxy-10 beta,13 alpha-diacetoxytaxa-4(20),11
      diene (2)], were isolated from an ethanol extract of the aerial parts of Taxus
      yunnanensis along with taxuspine B, 2-deacetoxytaxinine J, taxuyunnanine C,
      taxinine B, taxuspine C, and taxinine NN-4. The structures of 1 and 2 were
      established on the basis of 1D and 2D NMR and HRMS spectroscopic methods.

PMID- 11520231
TI  - Production of aromatic minimal polyketides by the daunorubicin polyketide
      synthase genes reveals the incompatibility of the heterologous DpsY and JadI
      cyclases.
AB  - Our investigations into whether the biosynthesis of a linearly fused ring system
      of an aromatic polyketide (jadomycin) could be modified to produce an angularly
      fused system (daunorubicin) and vice versa showed that introduction of the
      respective cyclases did not have the desired effect. Genes from the daunorubicin
      pathway produced a novel 21-carbon polyketide.

PMID- 11520232
TI  - Four new coumarin derivatives from Artemisia keiskeana.
AB  - Four new coumarin monoterpene ethers, artekeiskeanols A-D (1-4), and three known
      coumarins, isofraxidin, fraxidin, and daphnoretin, were isolated from the whole
      plants of Artemisia keiskeana. All structures were determined from spectral data,
      and that of artekeiskeanol A (1) was confirmed by synthesis.

PMID- 11520234
TI  - Uoamines A and B, piperidine alkaloids from the ascidian Aplidium uouo.
AB  - A specimen of the ascidian Aplidium uouo from Maui contained two piperidine
      alkaloids, uoamines A and B, that differed only in the geometry of a 3
      thiomethylacrylate ester group. The alkaloids exhibit conformational mobility in
      the NMR time frame, which complicated the elucidation of their structures by
      interpretation of spectroscopic data.

PMID- 11520233
TI  - Two phenanthraquinones from Dendrobium moniliforme.
AB  - Two phenanthraquinones were isolated from the stems of Dendrobium moniliforme.
      They were identified by interpretation of spectral data as 2,6-dimethoxy-1,4,5,8
      phenanthradiquinone and 5-hydroxy-3,7-dimethoxy-1,4-phenanthraquinone, named
      moniliformin (1) and denbinobin (2), respectively. This is the first report of
      compound 1, which possesses a novel 1,4,5,8-diquinone moiety in the
      phenanthraquinone skeleton. Compound 2 showed potent antiinflammatory effects in
      vitro.

PMID- 11520235
TI  - Isolation and structure of korolkoside, a bis-iridoid glucoside from Lonicera
      korolkovii.
AB  - A new bis-iridoid glucoside, korolkoside (1), was isolated from Lonicera
      korolkovii, and its structure and stereochemistry were determined by
      spectroscopic analysis and chemical derivatization. Korolkoside (1) consists of
      two secologanin moieties that are connected by an acetal linkage.

PMID- 11520236
TI  - Verbalactone, a new macrocyclic dimer lactone from the roots of Verbascum
      undulatum with antibacterial activity.
AB  - A novel macrocyclic dimer lactone, named verbalactone, was isolated from the
      roots of Verbascum undulatum and exhibited interesting antibacterial activity. It
      is the first time that 1,7-dioxacyclododecane is reported as the ring system of a
      natural product. The structure and the absolute stereochemistry of the new
      compound were determined by spectral methods and chemical correlation.

PMID- 11520238
TI  - Microbial transformation of pyrethrosin.
AB  - Microbial transformation of the germacranolide pyrethrosin (1) using Rhizopus
      nigricans NRRL 1477 has resulted in the isolation of 6 alpha-acetoxy-1 beta,4
      alpha-dihydroxy-5,7 alpha H,8 beta H-eudesm-11 beta,13-dihydro-8,12-olide (5), a
      new eudesmanolide-type metabolite, in addition to the previously reported
      eudesmanolides: 2, 3, 4, and 6. The structure elucidation of these metabolites
      was based primarily on 1D and 2D NMR analyses. The isolated metabolites exhibited
      cytotoxic, antifungal, and antiprotozoal activities.

PMID- 11520237
TI  - Samioside, a new phenylethanoid glycoside with free-radical scavenging and
      antimicrobial activities from Phlomis samia.
AB  - A new phenylethanoid glycoside, samioside, was isolated from the aerial parts of
      Phlomis samia and identified as 1-O-3,4-(dihydroxyphenyl)ethyl beta-D
      apiofuranosyl-(1-->4)-alpha-L-rhamnopyranosyl-(1-->3)-4-O-caffeoyl-beta-D
      glucopyranoside (1). In addition, one known phenylethanoid glycoside and three
      known flavonoids were identified as acteoside (2), apigenin, chrysoeriol, and
      ermanin, respectively. The structure of 1 was elucidated on the basis of its
      spectroscopic data. Samioside (1) demonstrated scavenging properties toward the
      DPPH radical and antimicrobial activity against Gram-positive and -negative
      bacteria.

PMID- 11520239
TI  - A novel modified pterin from a Eudistoma species ascidian.
AB  - The MeOH extract of an Indonesia Eudistoma sp. ascidian contained 1,3,O(7)
      trimethylisoxanthopterin (1), a novel pteridine. The purification of 1 was
      achieved through flash C(18) chromatography and cyano HPLC. The structure was
      determined primarily through the use of (1)H-(13)C and (1)H-(15)N HMBC
      measurements and comparison with data obtained for 1,3,7-trimethylguanine (2).

PMID- 11520240
TI  - Pacovatinins A-C, new labdane diterpenoids from the seeds of Renealmia exaltata.
AB  - Three new labdane diterpenoids, pacovatinins A-C (1-3), were isolated from seeds
      of the Brazilian medicinal plant Renealmia exaltata ("Pacova-catinga"), and their
      structures including absolute configurations were elucidated by spectroscopic
      data and a modified Mosher method.

PMID- 11520241
TI  - Four new isoflavone triglycosides from Sophora japonica.
AB  - Four new isoflavone triglycosides, genistein 7-O-beta-D-glucopyranoside-4'-O
      [(alpha-L-rhamnopyranosyl)-(1-->2)-beta-D-glucopyranoside] (1), genistein 7-O
      beta-D-glucopyranoside-4'-O-[(beta-D-glucopyranosyl)-(1-->2)-beta-D
      glucopyranoside] (2), genistein 7-O-alpha-L-rhamnopyranoside-4'-O-[(alpha-L
      rhamnopyranosyl)-(1-->2)-beta-D-glucopyranoside] (3), and genistein 7-O-alpha-L
      rhamnopyranoside-4'-O-[(beta-D-glucopyranosyl)-(1-->2)-beta-D-glucopyranoside]
      (4), together with nine known compounds, namely, genistein 7-O-beta-D
      glucopyranoside-4'-O-beta-D-glucopyranoside, sophorabioside, prunetin 4'-O-beta-D
      glucopyranoside, sophororicoside, genistin, rutin, kaempferol 3-O-beta
      rutinoside, quercetin 3-O-beta-D-glucopyranoside, and kaempferol 3-O-beta-D
      glucopyranoside, were isolated from the pericarps of Sophora japonica. The
      structures of 1-4 were determined by spectroscopic methods.

PMID- 11520242
TI  - New prenylhydroquinone glycosides from Phagnalon rupestre.
AB  - Three new hydroquinone glycosides were isolated from the MeOH extract of the
      aerial parts of Phagnalon rupestre. Their structures were elucidated as 1-O-beta
      glucopyranosyl-1,4-dihydroxy-2-(3',3'-dimethylallyl)benzene (1), 1-O-beta
      glucopyranosyl-1,4-dihydroxy-2-(3'-hydroxymethyl-3'-methylallyl)benzene (2), and
      1-O-(4' '-O-caffeoyl)-beta-glucopyranosyl-1,4-dihydroxy-2-(3',3'
      dimethylallyl)benzene (3) by spectroscopic methods.

PMID- 11520244
TI  - Insect antifeedant activity of three new tetranortriterpenoids from Trichilia
      pallida.
AB  - Three new tetranortriterpenoids, methyl 6-hydroxy-11 beta-acetoxy-12 alpha-(2
      methylpropanoyloxy)-3,7-dioxo-14 beta,15 beta-epoxy-1,5-meliacadien-29-oate (3),
      methyl 6,11 beta-dihydroxy-12 alpha-(2-methylpropanoyloxy)-3,7-dioxo-14 beta,15
      beta-epoxy-1,5-meliacadien-29-oate (4), and methyl 6-hydroxy-11 beta-acetoxy-12
      alpha-(2-methylbutanoyloxy)-3,7-dioxo-14 beta,15 beta-epoxy-1,5-meliacadien-29
      oate (5), have been isolated from the roots of Trichilia pallida. The related
      compounds hirtin (1) and deacetylhirtin (2) were also obtained. Compound 4 had
      the greatest antifeedant activity of 1-5 when tested against larvae of four
      species of Lepidoptera.

PMID- 11520243
TI  - Synthesis of 2-[4'-(ethylcarbamoyl)phenyl]-N-acetylglycine, the proposed
      structure for giganticine.
AB  - A compound (1) with the structure proposed for giganticine, an antifeedant
      principle isolated from the root bark of Caloropis gigantea, has been
      successfully synthesized by two independent methods. Comparison of physical
      properties and spectroscopic data of 1 with giganticine revealed that they are
      different compounds. All available evidence suggests that the proposed structure
      of giganticine is incorrect.

PMID- 11520245
TI  - Cytotoxicity of Ganoderma lucidum triterpenes.
AB  - Two new triterpenoids, lucidenic acid N (1) and methyl lucidenate F (2), together
      with four known compounds, lucidenic acid A, lucidenolactone, lucidenic acid C,
      and ganoderic acid E, were isolated from the dried fruiting bodies of Ganoderma
      lucidum. Their structures were elucidated by spectral and chemical transformation
      studies. Among them, lucidenic acid N (1), lucidenic acid A, and ganoderic acid E
      showed significant cytotoxic activity against Hep G2, Hep G2,2,15, and P-388
      tumor cells.

PMID- 11520246
TI  - Does Parkinson's disease have an immunological basis? The evidence and its
      therapeutic implications.
AB  - Parkinson's disease (PD) is an age-related neurodegenerative movement disorder of
      unknown aetiology. Immune abnormalities have been described in PD including the
      occurrence of autoantibodies against neuronal structures and high numbers of
      microglia cells expressing the histocompatibility glycoprotein human leucocyte
      antigen-DR in the substantia nigra. An infectious cause for PD has been discussed
      for years. Disturbed cellular and humoral immune functions in peripheral blood of
      patients with PD have been also reported. An elevated gammadelta(+) T cell
      population and increased immunoglobulin G immunity in CSF to heat shock proteins
      have been found in PD. Cytokines and apoptosis-related proteins were elevated in
      the striatum in patients with PD. Activated glial cells may participate in
      neuronal cell death in PD by providing toxic substances. We may conclude that the
      immune system is involved in the pathogenesis of PD. However, we are not able to
      determine whether the disturbances described above constitute a primary or
      secondary phenomenon. Immunomodulatory agents may have important applications in
      the development of new therapies for PD.

PMID- 11520247
TI  - Gene therapy for colorectal cancer: therapeutic potential.
AB  - Colorectal cancer is a leading cause of cancer mortality in Western countries.
      Gene therapy has been proposed as a potential novel treatment modality for
      colorectal cancer, but it is still in an early stage of development. The
      preclinical data have been promising and numerous clinical trials are underway.
      This brief review aims to summarise the current status of clinical trials of
      different gene therapy strategies, including immune stimulation, mutant gene
      correction, prodrug activation and oncolytic virus therapy, for patients with
      colorectal cancer. Data from phase I trials have proven the safety of the
      reagents but have not yet demonstrated significant therapeutic benefit. In order
      to achieve this and extend the scope of the treatment, continuing efforts should
      be made to improve the antitumour potency, efficiency of gene delivery and
      accuracy of gene targeting.

PMID- 11520248
TI  - Immunosuppressive treatment of ocular myasthenia gravis.
AB  - Myasthenia gravis (MG) is caused by autoantibodies against proteins at the
      neuromuscular junction. This autoimmune process leads to abnormal fatiguability
      and weakness of striated muscle. Ptosis and diplopia are among the most common
      manifestations of MG. The term "ocular MG" (OMG) as opposed to "generalised MG"
      (GMG) is used to define the clinical subtype of MG with isolated eye muscle
      weakness. Although OMG may appear to cause only moderate disability, it can
      significantly impair the patient's activities of daily living and progress to
      generalised myasthenia. Therefore, a clear management plan should be installed
      early in these patients. Since prospective treatment trials have not been
      performed, basic management strategies for OMG have to be deduced from
      retrospective studies, trials in GMG, and generally accepted clinical experience.
      Cholinesterase inhibitors are used in all types of MG, but are often less helpful
      in OMG. In the absence of thymoma, thymectomy is usually not considered in OMG,
      although a few studies have described histological abnormalities in thymuses from
      patients with OMG. Corticosteroids are of great short term benefit in most
      patients with OMG but potential adverse effects limit their long term use.
      Azathioprine is needed to reduce long term corticosteroid adverse effects, but
      this agent requires about 6 months to be effective. In summary, OMG has a good
      prognosis in most patients, with corticosteroids and azathioprine being the major
      treatment options. The challenges for the clinician are to recognise the
      condition despite the large number of differential diagnoses, to minimise the
      patient's symptoms using the therapies available and to carefully limit
      potentially hazardous therapeutic efforts, especially in mild or even uncertain
      cases.

PMID- 11520249
TI  - New therapeutic approaches to the management of rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is a common disease that affects up to 1% of the
      population, and causes significant morbidity and early mortality. The aetiology
      of RA is unknown; however, in the last 10 to 15 years significant advances in
      molecular technology have provided a greater understanding of the pathogenesis of
      the disease. This has led to the development of new approaches to the treatment
      of RA. The disease modifying antirheumatic oral agent leflunomide inhibits the
      proliferation of activated T cells that are important in the inflammation and
      degradation of synovial tissues. The 2 biological agents approved for the
      treatment of RA, infliximab and etanercept, are inhibitors of the pro
      inflammatory cytokine, tumour necrosis factor-alpha (TNFalpha). Infliximab is a
      chimeric human/mouse monoclonal antibody which is administered by intravenous
      infusion and binds with high affinity to TNFalpha, thereby neutralising its
      effects. Etanercept is a recombinant, soluble TNF receptor molecule which is
      administered subcutaneously and binds to TNFalpha in the serum rendering it
      biologically inactive. The protein A immunoadsorption column is a medical device
      that in conjunction with plasmapheresis can be used in patients with refractory
      RA. These agents have provided new and effective therapies for the treatment of
      patients with RA.

PMID- 11520250
TI  - The potential of monoclonal antibodies to reduce reperfusion injury in myocardial
      infarction.
AB  - Reperfusion injury is mediated, in part, by the accumulation of platelets and
      leucocytes in the microvasculature after reflow. These components of the blood
      pool form aggregates that can obstruct flow in small vessels. In addition,
      mediators released from leucocytes and platelets further damage the reperfused
      myocardium. A strategy to limit reperfusion injury exploits the important role of
      membrane-bound adhesion molecules that attach platelets and leucocytes to
      themselves and to the vascular endothelium. Monoclonal antibodies against
      specific adhesion receptors effectively eliminate the function of the receptor.
      The most widely investigated receptors are P-selectin, present on platelets and
      the endothelium, CD11/CD18, present on leucocytes, and the fibrinogen receptor on
      platelets. Numerous animal studies have strongly supported the use of these
      monoclonal antibodies to block adhesion receptors as adjunctive reperfusion
      therapy. However, recent human trials have yielded disappointing results.

PMID- 11520251
TI  - Systemic availability of inhaled budesonide and fluticasone propionate: healthy
      versus asthmatic lungs.
AB  - Inhaled corticosteroids are now recommended for the majority of patients with
      asthma. Although their therapeutic ratio is superior to that of oral
      corticosteroids, their long term use is associated with several potentially
      important adverse effects. A number of studies have compared the efficacy and/or
      systemic activity of the currently available inhaled corticosteroids, but the
      results of many of these studies have been conflicting. Although there are a
      number of factors that may explain these conflicting results, there is evidence
      that the type of individuals being studied is important. Extrapolation of the
      findings from healthy individuals to patients with asthma appears to be
      misleading because the systemic effects of some, but not all, inhaled
      corticosteroids are greater in healthy individuals than in patients with asthma.

PMID- 11520252
TI  - Antibody responses of healthy infants to concurrent administration of a bivalent
      haemophilus influenzae type b-hepatitis B vaccine with diphtheria-tetanus
      pertussis, polio and measles-mumps-rubella vaccines.
AB  - OBJECTIVE: To confirm that children given a bivalent Haemophilus influenzae type
      b-hepatitis B vaccine (bivalent Hib-HB vaccine; COMVAX) concurrently with priming
      doses of diphtheria-tetanus-pertussis vaccine (DTP), a booster dose of diphtheria
      tetanus-acellular pertussis vaccine (DTaP), inactivated or oral polio vaccine
      (IPV or OPV) and measles-mumps-rubella vaccine (M-M-R(II)) have satisfactory
      antibody responses to all antigens. DESIGN: 126 healthy 2-month-old infants were
      scheduled to receive bivalent Hib-HB vaccine concurrently with DTP (2 and 4
      months of age), OPV or IPV (random allocation to OPV or IPV at 2 months of age;
      OPV at 4 and 14 to 15 months of age), DTaP and M-M-R(II) (14 to 15 months of
      age). A response was judged "adequate" if the lower bound of the 95% confidence
      interval on the proportion of vaccinees having a critical antibody level was <10
      percentage points below prediction. RESULTS: Antibodies to hepatitis B virus
      surface antigen, H. influenzae polysaccharide, diphtheria toxin, tetanus toxin,
      pertussis agglutinogens, pertussis toxin (as measured by enzyme immunoassay but
      not by Chinese hamster ovary cell assay), pertussis filamentous haemagglutinin
      after a booster dose of DTaP, poliovirus type 2, measles virus, and mumps virus
      all equalled or exceeded expected levels. Antibodies to rubella virus and
      pertussis filamentous haemagglutinin (after priming doses of DTP) fell slightly,
      and in the case of rubella significantly, below predicted levels. Antibodies to
      poliovirus types 1 and 3 were also below expectation after 2 doses of polio
      vaccine but were adequate following a third dose of vaccine. CONCLUSION:
      Concurrent administration of bivalent Hib-HB vaccine with priming doses of DTP, a
      booster dose of DTaP, OPV, IPV, or M-M-R(II) was well tolerated and, with the
      possible exception of rubella, did not substantially impair the antibody response
      to any antigen.

PMID- 11520253
TI  - Development of pegylated interferons for the treatment of chronic hepatitis C.
AB  - The chemical attachment of poly(ethylene glycol) [PEG] to therapeutic proteins
      produces several benefits, including enhanced plasma half-life, lower toxicity,
      and increased drug stability and solubility. In certain instances, pegylation of
      a protein can increase its therapeutic efficacy by reducing the ability of the
      immune system to detect and mount an attack on the compound. A PEG-protein
      conjugate is formed by first activating the PEG moiety so that it will react
      with, and couple to, the protein. PEG moieties vary considerably in molecular
      weight and conformation, with the early moieties (monofunctional PEGs; mPEGs)
      being linear with molecular weights of 12kD or less, and later moieties being of
      increased molecular weights. PEG2, a recent innovation in PEG technology,
      involves the coupling of a 30kD (or less) mPEG to lysine that is further reacted
      to form a branched structure that behaves like a linear mPEG of much larger
      molecular weight. These compounds are pH and temperature stable, and this factor
      along with the large molecular weight may account for the restricted volume of
      distribution seen with drugs utilising these reagents. Three PEG-protein
      conjugates are currently approved for clinical use in the US, with more under
      clinical development. Pegademase is used in the treatment of severe combined
      immunodeficiency disease, pegaspargase for the treatment of various leukaemias,
      and pegylated interferon-alpha for chronic hepatitis C virus infections. As
      illustrated in the case of the 2 pegylated interferon-alphas, all pegylated
      proteins are not equal. The choice of PEG reagent and coupling chemistry is
      critical to the properties of the PEG-protein conjugate, with the molecular
      weight of the moiety affecting its rate and route of clearance from the body, and
      coupling chemistry affecting the strength of the covalent attachment of PEG to
      therapeutic protein.

PMID- 11520254
TI  - Therapeutic advances in biological response modifiers in the treatment of
      cutaneous T-cell lymphoma.
AB  - Cutaneous T-cell lymphoma (CTCL) is most often a skin-infiltrating malignancy of
      clonal CD4+ T-cells. Therapy is based on staging and the likelihood of
      progression. Biological response modifiers and chemotherapeutic agents are used
      to preserve the integrity of the host antitumour response while selectively
      targeting the malignant cells. The biological response-modifying treatment
      options currently used to treat CTCL are bexarotene, denileukin diftitox,
      interferon-alpha, interferon-gamma and interleukin-12, as well as extracorporeal
      photopheresis and phototherapy. A combination therapy approach maximises response
      in patients with advanced CTCL. Biological response modifiers in combination with
      photopheresis are used for patients with the leukaemic phase of the disease.
      Among the majority of patients with advanced stage disease so treated, immune
      response augmentation appears to prolong survival. Future areas of research
      should assess not only survival and optimal treatment combinations, but also
      quality of life during the treatment period.

PMID- 11520255
TI  - Molecular biology of pancreatic cancer: potential clinical implications.
AB  - The development of cancer involves the accumulation of genetic changes. Over the
      past decade there has a been spectacular advance in the knowledge of the genetic
      basis of cancer, mainly as a result of the rapid progression of molecular
      technology. Pancreatic cancer is one of the most lethal cancers. Conventional
      therapeutic approaches have not had much impact on the course of this aggressive
      neoplasm. Knowledge of the molecular biology of pancreatic cancer has grown
      rapidly. Genetic alterations in pancreatic cancer include oncogene mutations
      (most commonly K-ras mutations), and tumour suppressor gene alterations (mainly
      p53, p16, DCC, etc.). These advances have potential implications for the
      management of this deadly disease. Identification of a hereditary genetic
      predisposition to pancreatic cancer has led to the formation of pancreatic cancer
      registries around the world, with voluntary screening of patients and siblings
      for the hereditary genetic defect. Asymptomatic population screening remains
      unrealistic, but the recognition of subpopulations at increased risk from
      pancreatic cancer, along with novel and sensitive detection techniques, means
      that targeted population screening is a step closer. Intensive research is
      performed in specialist laboratories to improve the diagnostic approach in
      patients with pancreatic cancer. The use of such molecular diagnostic methods is
      likely to expand. Molecular biology may also have a great impact on the treatment
      of pancreatic cancer, and many therapeutic approaches are being evaluated in
      clinical trials, including gene replacement therapy, genetic prodrug activation
      therapy, antisense immunology and peptide technology. The 'molecular age' has the
      promise of delivering still better results. This review summarises recent data
      relating to the molecular biology of pancreatic cancer, with emphasis on features
      that may be of clinical significance for diagnosis and/or therapy.

PMID- 11520256
TI  - Clinical prescribing of allergic rhinitis medication in the preschool and young
      school-age child: what are the options?
AB  - Allergic rhinitis (AR) is the most common chronic condition in children and is
      estimated to affect up to 40% of all children. It is usually diagnosed by the age
      of 6 years. The major impact in children is due to co-morbidity of sinusitis,
      otitis media with effusion, and bronchial asthma. AR also has profound effects on
      school absenteeism, performance and quality of life. Pharmacotherapy for AR
      should be based on the severity and duration of signs and symptoms. For mild,
      intermittent symptoms lasting a few hours to a few days, an oral second
      generation antihistamine should be used on an as-needed basis. This is preferable
      to a less expensive first-generation antihistamine because of the effect of the
      latter on sedation and cognition. Four second-generation antihistamines are
      currently available for children under 12 years of age: cetirizine, loratadine,
      fexofenadine and azelastine nasal spray; each has been found to be well tolerated
      and effective. There are no clearcut advantages to distinguish these
      antihistamines, although for children under 5 years of age, only cetirizine and
      loratadine are approved. Other agents include pseudoephedrine, an oral
      vasoconstrictor, for nasal congestion, and the anticholinergic nasal spray
      ipratropium bromide for rhinorrhoea. Sodium cromoglycate, a mast cell stabiliser
      nasal spray, may also be useful in this population. For patients with more
      persistent, severe symptoms, intranasal corticosteroids are indicated, although
      one might consider azelastine nasal spray, which has anti- inflammatory activity
      in addition to its antihistamine effect. With the exception of fluticasone
      propionate for children aged 4 years and older, and mometasone furoate for those
      aged 3 years and older, the other intranasal corticosteroids including
      beclomethasone dipropionate, triamcinolone, flunisolide and budesonide are
      approved for children aged 6 years and older. All are effective, so a major
      consideration would be cost and safety. For short term therapy of 1 to 2 months,
      the first-generation intranasal corticosteroids (beclomethasone dipropionate,
      triamcinolone, budesonide and flunisolide) could be used, and mometasone furoate
      and fluticasone propionate could be considered for longer-term treatment.
      Although somewhat more costly, these second-generation drugs have lower
      bioavailability and thus would have a better safety profile. In patients not
      responding to the above programme or who require continuous medication,
      identification of specific triggers by an allergist can allow for specific
      avoidance measures and/or immunotherapy to decrease the allergic component and
      increase the effectiveness of the pharmacological regimen.

PMID- 11520257
TI  - Silymarin: a review of its clinical properties in the management of hepatic
      disorders.
AB  - The mechanisms of action of silymarin involve different biochemical events, such
      as the stimulation of the synthetic rate of ribosomal RNA (rRNA) species through
      stimulation of polymerase I and rRNA transcription, protecting the cell membrane
      from radical-induced damage and blockage of the uptake of toxins such as alpha
      amanitin. Studies in patients with liver disease have shown that silymarin
      increases superoxide dismutase (SOD) activity of lymphocytes and erythrocytes, as
      well as the expression of SOD in lymphocytes. Silymarin has also been shown to
      increase patient serum levels of glutathione and glutathione peroxidase. Silybin
      20 to 48 mg/kg/day has shown promise as a clinical antidote to acute Amanita
      (deathcap mushroom) poisoning. Primary efficacy data from 3 trials which examined
      the therapeutic potential of silymarin in patients with cirrhosis, and included
      patient survival as an end-point, demonstrated that silymarin had no significant
      beneficial effect on patient mortality. However, upon subanalysis, silymarin 420
      mg/day had a significantly beneficial effect on patient survival rate (compared
      with patients receiving placebo) in 1 randomised, double-blind trial in patients
      with alcoholic cirrhosis. Silymarin 420 mg/day was also shown to improve indices
      of liver function [AST, ALT, gamma-glutamyl transferase and bilirubin] in
      patients with liver disease of various aetiology, including those exposed to
      toxic levels of toluene or xylene; however, it was largely ineffective in
      patients with viral hepatitis. Reports of adverse events while receiving
      silymarin therapy are rare. However, there have been accounts of nausea,
      epigastric discomfort, arthralgia, pruritus, headache and urticaria. Silymarin
      has also been reported to have possibly caused a mild laxative effect.
      CONCLUSION: The antioxidant properties of silymarin (a mixture of at least 4
      closely related flavonolignans, 60 to 70% of which is a mixture of 2
      diastereomers of silybin) have been demonstrated in vitro and in animal and human
      studies. However, studies evaluating relevant health outcomes associated with
      these properties are lacking. Although silymarin has low oral absorption, oral
      dosages of 420 mg/day have shown some therapeutic potential, with good
      tolerability, in the treatment of alcoholic cirrhosis. Moreover, silybin 20 to 48
      mg/kg/day has shown promise as an antidote for acute mushroom poisoning by
      Amanita phalloides; however, further studies paying attention to the amount of
      ingested mushroom and time elapsed before administration of treatment are needed
      to clarify its role in this indication. Studies in patients with the early onset
      of liver disease may demonstrate the liver regeneration properties that silymarin
      is promoted as possessing.

PMID- 11520261
TI  - Multifocal glomangiomyomas in the chest wall of a young man.

PMID- 11520262
TI  - The legacy of Robert Koch.

PMID- 11520263
TI  - Six-year trends in productivity and utilization of 73 clinical laboratories: a
      College of American Pathologists Laboratory Management Index Program study.
AB  - OBJECTIVES: To describe longitudinal trends in the efficiency, labor
      productivity, and utilization of clinical laboratories in the United States.
      METHODS: Financial and activity data were prospectively collected from 73
      clinical laboratories continuously enrolled in the College of American
      Pathologists Laboratory Management Index Program from 1994 through 1999. Each
      laboratory reported quarterly on its costs, labor inputs, and test activity using
      uniform data definitions. RESULTS: During the 6-year study period, there was a
      significant increase in laboratory labor productivity (2.1% more tests/full-time
      equivalent/y; P <.001). Productivity increases were offset by increasing labor
      expense (1.5%/full-time equivalent/y; P <.001), consumable expense (1.7%/on-site
      test/y; P =.005), and blood expense, which comprised more than 10% of laboratory
      expenses by 1999 (4.4% increase/y; P <.001). As a result, overall expense per
      test showed no significant change in non-inflation-adjusted dollars. Reference
      laboratory expense per test did not change significantly during the study period;
      the proportion of tests sent to reference laboratories grew slightly (0.06%
      increase/y; P <.001). Test volume of the median laboratory grew by 5442 tests per
      year (2.3% annual increase; P <.001), while the proportion of testing from
      inpatients declined by 1.7% per year (P <.001). Inpatient test utilization
      declined on a discharge basis (annual decline of 1.2 tests/inpatient discharge; P
      <.001) and on a per diem basis (annual decline of 0.08 tests/inpatient day; P
      =.002). Inpatient laboratory expense declined on a discharge basis (annual
      decline of $2.40 or 1.3% per discharge; P <.001), but did not change
      significantly per inpatient day. Most of the reduction in the expense per
      discharge occurred during 1994-1996. CONCLUSIONS: Between 1994 and 1999, clinical
      laboratories in the United States experienced significant changes in the cost of
      operations, utilization, and labor productivity. Laboratory administrators who
      compare local institutional performance with that of peers are advised to use
      current or forward-trended peer data. Quarter-to-quarter improvement in many
      measures of laboratory financial activity may not signal a superior operation, as
      performance of the whole industry appears to be improving.

PMID- 11520264
TI  - Protocol for the examination of specimens from patients with tumors of the
      brain/spinal cord: a basis for checklists.

PMID- 11520265
TI  - Protocol for the examination of specimens from patients with carcinomas of the
      skin, excluding eyelid, vulva, and penis: a basis for checklists.

PMID- 11520266
TI  - Protocol for the examination of specimens from patients with tumors of the
      peritoneum: a basis for checklists.

PMID- 11520267
TI  - Protocol for the examination of specimens from patients with uveal melanoma: a
      basis for checklists.

PMID- 11520268
TI  - Protocol for the examination of specimens from patients with retinoblastoma: a
      basis for checklists.

PMID- 11520269
TI  - Confidentiality of health information postmortem.
AB  - CONTEXT: Recent discussions of health care privacy have prompted new concerns
      over the control of private health information after a patient's death. The
      importance of confidentiality protections postmortem is compounded as genetic
      technologies and research capabilities advance and public interest in this
      information increases. OBJECTIVE: The Council on Ethical and Judicial Affairs of
      the American Medical Association developed this report to guide physicians in the
      management of patients' health information postmortem. PARTICIPANTS: This report
      was developed by the 9 physician members of the Council on Ethical and Judicial
      Affairs with the assistance of staff from the Ethics Standards Group at the
      American Medical Association. EVIDENCE: Literature searches in the MEDLINE and
      BIOETHICSLINE databases using the search terms postmortem and health information
      qualified with confidentiality or privacy yielded a combined total of 129
      references. Additional references were culled from policies of a number of health
      care organizations. CONSENSUS PROCESS: The Council on Ethical and Judicial
      Affairs solicited suggestions from the federation of state medical and specialty
      societies before drafting this report. A copy of the report was sent to the
      College of American Pathologists for comment. It was then adopted by a majority
      vote of the House of Delegates of the American Medical Association. CONCLUSIONS:
      The report emphasizes the importance of maintaining confidentiality for
      information held within a deceased patient's medical record. However, these
      protections are subject to certain exceptions. Confidentiality can be upheld when
      such information is used for educational or research purposes by removing
      individual identifiers. For disclosures in which the identity of the deceased
      patient is known, a number of considerations are provided to assess when
      disclosure would be ethically permissible.

PMID- 11520270
TI  - Unexpected autopsy findings arising from postmortem ocular examination.
AB  - BACKGROUND: A full autopsy at our institution includes removal of the eyes for
      pathologic examination. To our knowledge, the rate of ophthalmic findings at
      autopsy has not been documented previously. DESIGN: We retrospectively reviewed
      277 consecutive autopsies conducted between 1995 and 1999 in which the eyes were
      removed for examination. Ophthalmic findings were placed in the following
      categories: I, major findings included those that contributed to the patient's
      death, would have changed patient management, and/or may have important medical
      implications for close relatives; II, expected findings after ophthalmologic
      surgery and minor findings that may have eventually required treatment; and III,
      incidental findings. RESULTS: Major findings (category I) were found in 32% of
      autopsies. Minor findings (category II) and incidental findings (category III)
      were documented in 62% and 34% of autopsies, respectively. Only 14% of autopsies
      revealed no ophthalmologic diagnoses. CONCLUSION: In our series, postmortem
      ocular examination revealed a number of important findings, including several
      heritable and rare conditions. Eighty-six percent of autopsies disclosed at least
      one pathologic ophthalmologic finding, approximately one third of which
      demonstrated findings significant enough to have likely required management.
      Diabetic retinopathy was the most frequent major finding. Malignant melanoma of
      the choroid was the most commonly found intraocular neoplasm. Chronic uveitis was
      the most common minor finding. We conclude that important, often unexpected
      ophthalmic findings are frequently encountered at autopsy, underscoring the
      relevance of routine postmortem examination of the eyes.

PMID- 11520272
TI  - Differential expression of ras signal transduction mediators in verrucous and
      squamous cell carcinomas of the upper aerodigestive tract.
AB  - CONTEXT: ras gene mutations and expression of its gene product have been
      described in verrucous and squamous cell carcinomas. Other downstream signal
      transduction mediators, extracellular signal-regulated kinases 1 and 2 (ERK-1 and
      ERK-2) and Raf-1, have not yet been as extensively studied. OBJECTIVE: To
      determine patterns of expression of ERK-1, ERK-2, and Raf-1 in verrucous and
      squamous cell carcinomas of the upper aerodigestive tract. DESIGN: Seventeen
      verrucous carcinomas and 10 squamous cell carcinomas of the upper aerodigestive
      tract were examined for the immunohistochemical expression of ERK-1, ERK-2, and
      Raf-1 product. RESULTS: Raf-1 expression was intensely expressed in the most
      basal portions of the epithelium in verrucous carcinomas, but was minimally
      expressed in the suprabasalar areas. Anti-Raf-1 staining of the squamous cell
      carcinomas was diffuse and patchy throughout the tumor cells and was weak in
      intensity. There was no geographic preference of staining. The cytoplasmic
      expression of both ERK-1 and ERK-2 was predominantly negative in the most basal
      layers of the epithelium in the verrucous carcinomas, but was positive in the
      suprabasalar region of the epithelium. Immunohistochemical expression of ERK-1
      and ERK-2 in the squamous carcinomas was diffuse throughout the tumor.
      CONCLUSION: There is strong correlation of the geographic expression of these
      mediators of ras signal transduction in verrucous and squamous carcinomas, but
      the cause of these differences remains unclear at present. The expression of
      these mediator proteins may have potential for diagnosis, as well as in
      understanding the biologic behavior of these lesions.

PMID- 11520271
TI  - Conserved genetic findings in metastatic bladder cancer: a possible utility of
      allelic loss of chromosomes 9p21 and 17p13 in diagnosis.
AB  - CONTEXT: Molecular analysis of microsatellite alterations of biologically
      distinct tumor cell subpopulations from the same patient may aid in the
      determination of tumor origin and further our understanding of the genetic basis
      of cancer progression. DESIGN: The authors examined the pattern of allelic loss
      with polymorphic microsatellite markers on chromosome 9p21 (D9S161, D9S171,
      IFNA), regions of putative tumor suppressor gene p16, and on chromosome 17p13
      (TP53), the p53 locus, in matched primary and metastatic bladder cancers from 9
      patients. All patients underwent cystectomy for bladder cancer and had regional
      lymph node metastases at the time of surgery. Genomic DNA was prepared from
      primary cancers and matched synchronous lymph node metastases using a
      microdissection method. RESULTS: The overall frequency of allelic loss was 78% in
      primary cancer and 89% in paired metastatic cancer. The frequency of allelic loss
      in the primary cancer was 86% with D9S161, 67% with D9S171, 71% with IFNA, and
      80% with TP53. The frequency of allelic loss in matched metastatic cancer was
      100% with D9S161, 62% with D9S171, 71% with IFNA, and 80% with TP53. An identical
      pattern of allelic imbalance (allelic loss or retention) at multiple DNA loci was
      observed in matched primary and metastatic carcinoma in 8 (88%) cases. One case
      showed allelic loss in the metastasis, but not in the primary cancer.
      CONCLUSIONS: The pattern of allelic loss at chromosome 9p21 (p16) and 17p13 (p53)
      was generally maintained during cancer progression to metastasis, and identical
      allelic loss in primary cancer was conserved in paired metastatic carcinoma.
      These data suggest that these genetic changes may be useful in establishing a
      diagnosis and determining tumor origins in difficult cases.

PMID- 11520273
TI  - Quantitative microbiologic study of blood salvaged by intraoperative membrane
      filtration.
AB  - OBJECTIVE: To evaluate the sterility of blood salvaged intraoperatively by a new
      membrane filtration system for transfusion. DESIGN: Quantitative microbiologic
      cultures were prospectively collected from units of blood acquired by
      intraoperative membrane filtration from 18 patients undergoing elective spinal
      surgery. Medical records were reviewed for adverse events. SETTING: A 204-bed,
      medical school-affiliated community hospital. RESULTS: Quantitative blood
      cultures were sterile in 12 of 31 units of recovered blood. Of the 19 positive
      units, 17 units grew only 1 colony-forming unit (CFU)/mL, 1 unit grew 2 CFU/mL,
      and 1 unit grew 5 CFU/mL. The only organisms isolated were diphtheroids,
      coagulase-negative staphylococci, and micrococci. No patient experienced
      postoperative sepsis. CONCLUSIONS: Blood recovered by intraoperative membrane
      filtration is microbiologically equivalent to blood salvaged by continuous flow.
      Because no perfusionist and no expensive capital equipment are required, the
      technique is amenable to small and medium-sized hospitals that otherwise might
      financially be unable to provide intraoperative blood salvage.

PMID- 11520274
TI  - Aberrant expression of tumor suppressor proteins in the Ewing family of tumors.
AB  - BACKGROUND: Deregulation of tumor suppressor gene function and abrogation of cell
      cycle control are common features of malignant neoplasms, but corresponding data
      on Ewing sarcomas and primitive neuroectodermal tumors are relatively scarce. We
      studied the expression of 4 tumor suppressor proteins in the Ewing family of
      tumors (EFTs). DESIGN: We examined a series of 20 pediatric EFTs for abnormal
      expression of p16(INK4a), p14(ARF), p21(WAF1), and pRB by immunohistochemical
      analysis of pretreatment, nondecalcified archival specimens. Clinical follow up
      was available in all cases (median, 21 months; range, 5-103 months). Five
      patients presented with metastatic disease, 8 had no evidence of disease at last
      follow up, and 12 had an adverse outcome (death or progressive tumor
      posttherapy). RESULTS: Twelve cases (60%) demonstrated abnormal expression of at
      least one tumor suppressor protein. There were 11 cases (55%) with loss of
      p21(WAF1) expression, 4 (20%) with down-regulation of p16(INK4a), 2 (10%) with
      absence of pRB, and one case (5%) with loss of p14(ARF) expression. Loss of
      p16(INK4a) expression correlated with metastatic disease at presentation (P
      =.026), and showed a trend toward shortened survival (P =.20). The p21(WAF1),
      p14(ARF), and pRB status was not significantly correlated with either metastatic
      disease at presentation or outcome. CONCLUSION: Abrogation of the G1 checkpoint
      was common in this series of EFTs, and down-regulation of p21(WAF1) and
      p16(INK4a) were the most frequent findings. Loss of p16(INK4a) expression may
      identify a subset of cases with a more aggressive phenotype.

PMID- 11520276
TI  - Ganglioneuroma of parapharyngeal region.
AB  - In this article, we describe a case of ganglioneuroma observed in a 27-year-old
      woman. The tumor was found in an unusual location, the parapharyngeal space. The
      lesion was asymptomatic and was surgically excised after a fine-needle aspiration
      biopsy that was considered inadequate. The lesion measured 4 x 3 cm and was
      capsulated. Two distinct cells groups were identified: ganglion cells and Schwann
      cells placed in a loose myxoid stroma. Immunohistochemical stains (performed with
      the following monoclonal antibodies: high-molecular-weight cytokeratins,
      vimentin, neuron-specific enolase, neurofilaments, and S100) confirmed the
      diagnosis of ganglioneuroma. The pathologic findings and a review of recent
      literature are discussed.

PMID- 11520275
TI  - The effect of changes in laboratory practices on the rate of false-positive
      cultures for Mycobacterium tuberculosis.
AB  - CONTEXT: False-positive cultures for Mycobacterium tuberculosis have been found
      in nearly all DNA fingerprinting studies, but the effectiveness of interventions
      to reduce cross-contamination has not been evaluated. OBJECTIVE: To evaluate
      whether changes in laboratory policies and procedures reduced the rate of false
      positive cultures. DESIGN: Retrospective study of isolates with matching DNA
      fingerprints. SETTING: A mycobacteriology laboratory serving an urban
      tuberculosis control program and public hospital system. PATIENTS: All M
      tuberculosis isolates processed from July 1994 to December 1999. METHODS:
      Isolates were fingerprinted using IS6110; pTBN12 was used to fingerprint isolates
      having fewer than 6 copies of IS6110. We further evaluated all patients having
      only one positive culture whose DNA fingerprint matched that of another isolate
      processed in the laboratory within 42 days. INTERVENTIONS: We changed laboratory
      policy to reduce the number of smear-positive specimens processed and changed
      laboratory procedures to minimize the risk of cross-contamination during batch
      processing. MAIN OUTCOME MEASURE: The rate of false-positive cultures. RESULTS:
      Of 13 940 specimens processed during the study period, 630 (4.5%) from 184
      patients and 48 laboratory proficiency specimens grew M tuberculosis. There were
      no cases (0/184) of probable or definite cross-contamination, compared with the
      4% rate (8/199) identified in our previous study (P =.008). We also fingerprinted
      a convenience sample of isolates from other laboratories in Denver; 13.6% (3/22)
      of these were false-positive, a rate similar to the 11.9% rate (5/42) identified
      for other laboratories in our previous study (P =.84). CONCLUSIONS: Laboratory
      cross-contamination decreased significantly after relatively simple, inexpensive
      changes in laboratory policies and practices. Cross-contamination continued to
      occur in other laboratories in Denver.

PMID- 11520278
TI  - Diagnosis of chondroid lipoma by fine-needle aspiration biopsy.
AB  - Chondroid lipoma is a rare, recently described soft tissue tumor that mimics
      extraskeletal chondrosarcoma and myxoid liposarcoma. Reports regarding its
      cytologic and radiological features are sparse. In this report, we describe the
      cytologic features of this unusual tumor, which include mixed mature lipocytes
      and lipoblast-like cells embedded in chondromyxoid matrix. We also describe the
      "target sign appearance" of this tumor in magnetic resonance imaging studies,
      resembling a neurogenic tumor. More importantly, we demonstrate that a definitive
      diagnosis of this unusual tumor can be made by fine-needle aspiration biopsy. The
      usefulness of cell block in fine-needle aspiration biopsy diagnosis of soft
      tissue tumors is emphasized.

PMID- 11520277
TI  - Three-dimensional organization of the hepatic microvasculature in hereditary
      hemorrhagic telangiectasia.
AB  - Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant systemic
      fibrovascular dysplasia. Although hepatic vascular shunts are often observed in
      HHT, the responsible pathological mechanism is unknown. This issue was addressed
      by performing a 3-dimensional reconstruction study of the hepatic
      microvasculature of an HHT-involved liver in a 79-year-old woman. Clinical
      observation revealed high-output congestive heart failure and hepatic
      encephalopathy due to arteriovenous and portovenous shunts, respectively.
      Angiography revealed tortuous dilation of hepatic arterial branches and
      intrahepatic arteriovenous shunts. The 3-dimensional analysis of the autopsy
      liver revealed focal sinusoidal ectasia, arteriovenous shunts through abnormal
      direct communications between arterioles and ectatic sinusoids, and portovenous
      shunts due to frequent and large communications between portal veins and ectatic
      sinusoids. Type 1 HHT was suggested by the lack of endoglin immunoreactivity in
      the liver. The 3-dimensional reconstruction study of hepatic microvasculature was
      successful in identifying the pathological changes responsible for the
      intrahepatic shunts in HHT.

PMID- 11520281
TI  - Clear cell variant of fibrolamellar carcinoma of the liver.
AB  - Fibrolamellar carcinoma of the liver is a distinctive variant of hepatocellular
      carcinoma characterized histologically by trabeculae of oncocytic cells with
      intervening lamellae of collagen fibers. We describe a case with a prominent
      component of clear cells, a feature not previously recognized in this tumor type.
      The patient was a 59-year-old woman incidentally found to have a solitary liver
      tumor, measuring 5 cm. Pathologic examination revealed a circumscribed, firm, tan
      tumor with peculiar concentric streaks. Oncocytic cells and clear cells were
      arranged in trabeculae separated by lamellae of collagen or sinusoids. The clear
      cells possessed abundant finely reticulated clear cytoplasm, which was
      highlighted by trichrome stain and immunostaining with antimitochondria antibody.
      Ultrastructurally, the cytoplasm of the clear cells was packed with empty
      membrane-bound vesicles that occasionally contained short cristae. The features
      suggested that the clear cell change resulted from ballooning and rarefactive
      changes of mitochondria. Clear cell fibrolamellar carcinoma should not be
      confused with conventional clear cell hepatocellular carcinoma, since the former
      is associated with a more favorable prognosis.

PMID- 11520279
TI  - CD15(+) acute lymphoblastic leukemia and subsequent monoblastic leukemia:
      persistence of t(4;11) abnormality and B-cell gene rearrangement.
AB  - The abnormality in the translocation of chromosomes 4 and 11 (t[4;11]) has been
      characteristically associated with calla-negative CD15(+) acute lymphoblastic
      leukemia (ALL) of early pre-B-cell origin. Transformation of a lymphoblastoid to
      a monoblastoid morphologic structure has rarely been described at relapse in
      these cases; however, these cases have lacked flow cytometric immunophenotyping
      (FCI) and genotypic studies (GS) to define the immunophenotype of and the
      presence of a B-cell gene rearrangement in the monoblastoid component. We report
      a case of CD15(+), CD10(-) ALL of early pre-B-cell origin defined by morphologic
      testing and FCI with the t(4;11) abnormality. At relapse, the morphologic
      testing, enzyme cytochemistry, and FCI data were characteristic of monoblastic
      leukemia. The t(4;11) abnormality persisted with associated additional
      chromosomal abnormalities, and the monoblasts contained a B-cell gene
      rearrangement by GS. These findings support the concept that both processes arose
      from a multipotential progenitor cell.

PMID- 11520282
TI  - Renal cell carcinoma with intravascular lymphomatosis: a case report of unusual
      collision tumors with review of the literature.
AB  - We report the case of a 77-year-old white woman who presented with a left breast
      mass, lethargy, and weight loss. Pelvic computed tomographic scan revealed a 9.5
      cm mass in the right kidney. Surgical pathology demonstrated a diffuse large B
      cell lymphoma of the subcutaneous tissue of the breast and renal cell carcinoma
      with concurrent extensive intravascular lymphomatosis. Systemic dissemination of
      malignant lymphoma to a concurrent visceral primary neoplasm is rare. To the best
      of our knowledge, this is the first case illustrating a renal cell carcinoma
      collision with intravascular lymphomatosis.

PMID- 11520280
TI  - A high-grade primary leiomyosarcoma of the bladder in a survivor of
      retinoblastoma.
AB  - Second nonocular malignancies develop with increased incidence in patients with
      hereditary retinoblastoma. Osteosarcoma is by far the most common type with an
      incidence of up to 50%, followed by soft tissue sarcomas. Visceral leiomyosarcoma
      is extremely rare and only 2 cases have been reported in the past 2 decades, one
      in the liver and another one in the urinary bladder, both of which developed
      after cyclophosphamide therapy. Here we report a case of vesical leiomyosarcoma
      that was diagnosed in a 49-year-old woman 47 years after the diagnosis of a
      hereditary retinoblastoma. The patient's retinoblastoma was treated with
      unilateral enucleation without adjuvant radiation or chemotherapy. We believe
      that this is the first report of vesical leiomyosarcoma occurring in a patient
      with retinoblastoma without a prior history of radiation or chemotherapy. This
      report is significant not only because of the rarity of vesical leiomyosarcoma as
      a second nonocular tumor in retinoblastoma patients, but also because of the
      infrequency of vesical leiomyosarcoma in general. We also investigated the
      potential molecular pathogenesis of the leiomyosarcoma.

PMID- 11520283
TI  - Pigmented papillary epithelial neoplasm of the pituitary fossa: a distinct lesion
      of uncertain histogenesis.
AB  - Primary pigmented intracranial neoplasms are strikingly uncommon. The
      differential diagnosis is limited and includes both epithelial and nonepithelial
      tumors, most of which arise within or near the ventricular system. The authors
      describe a 42-year-old man who presented with a pigmented papillary epithelial
      lesion that arose within the sella and exhibited suprasellar extension and bony
      erosion. Following external beam radiotherapy and multiple surgical resections,
      tumor growth became rapid, necessitating additional debulking procedures.
      Pathologic evaluation of subsequent lesional tissue samples revealed an
      anaplastic lesion with malignant epithelial and spindle cell components.
      Occasional epithelial cells showed features reminiscent of the original papillary
      lesion, whereas others exhibited oncocytic morphologic features. This case
      represents the only report, to our knowledge, of a pigmented papillary epithelial
      neoplasm arising within the pituitary fossa. Although the histogenesis of this
      tumor is enigmatic, this appears to be a distinct lesion characterized by
      aggressive growth and the capacity for anaplastic progression.

PMID- 11520285
TI  - Pathologic quiz case: an 86-year-old woman with refractory anemia.

PMID- 11520284
TI  - Association of primary pleural effusion lymphoma of T-cell origin and human
      herpesvirus 8 in a human immunodeficiency virus-seronegative man.
AB  - We describe a case of an 87-year-old human immunodeficiency virus (HIV)-negative
      man who developed a primary pleural lymphoma without any identifiable tumor mass
      associated with human herpesvirus 8 (HHV-8) infection. A large T-cell lymphoma
      was diagnosed based on morphologic, immunophenotypic, and molecular findings. The
      HHV-8 DNA sequences were detected using specific polymerase chain reaction
      amplification in the lymphomatous effusion. Study of the patient's serum
      confirmed the HHV-8 infection. This case report displays the characteristic
      features of HHV-8-related body cavity-based lymphoma/primary effusion lymphoma
      previously reported in HIV-seronegative patients, except that it is of T-cell
      origin. Whether this case may be included or not within the primary effusion
      lymphoma entity, the association of a pleural T-cell non-Hodgkin lymphoma with
      HHV-8 infection raises the question of the possible occurrence of T cells as the
      target of malignant transformation associated with HHV-8 infection.

PMID- 11520286
TI  - Pathologic quiz case: a 76-year-old man with abdominal pain and rapidly
      progressive course.

PMID- 11520287
TI  - Pathologic quiz case: a healthy 31-year-old-man with sinusitis.

PMID- 11520288
TI  - Pathologic quiz case: a retroperitoneal mass in a young woman.

PMID- 11520289
TI  - Polypoid endometriosis.

PMID- 11520290
TI  - Placental chorangiosis.

PMID- 11520291
TI  - Microinvasive carcinoma of breast: a commonly misdiagnosed entity.

PMID- 11520292
TI  - Acid-fast serpentine cords of Mycobacterium tuberculosis.

PMID- 11520301
TI  - Insulin resistance and beta-cell dysfunction as therapeutic targets in type 2
      diabetes.

PMID- 11520302
TI  - N-phenacylthiazolium bromide decreases renal and increases urinary advanced
      glycation end products excretion without ameliorating diabetic nephropathy in
      C57BL/6 mice.
AB  - AIMS: Advanced glycation end products (AGE), which form from the non-enzymatic
      reaction of proteins and sugars, have been implicated in the pathogenesis of
      diabetic nephropathy. Recently, a compound [N-phenacylthiazolium bromide (PTB)]
      has been described which cleaves alpha,beta-dicarbonyl compounds. In the present
      study we used diabetic C57BL/6 mice to determine if PTB altered renal AGE levels
      and reduced diabetic glomerulosclerosis. METHODS: Mice with stable hyperglycaemia
      induced by streptozotocin were given daily subcutaneous injections of either PTB
      (10 microg/g) or saline for 12 weeks. Renal-collagen bound AGE and urinary AGE
      peptides were measured by ELISA using an anti-AGE-RNase antibody. Renal collagen
      released Nepsilon(carboxymethyl)lysine (CML) and pentosidine were determined by
      high pressure liquid chromatography (HPLC). Glomerular lesions (volume and
      mesangial/total surface area) were evaluated by computer-assisted image analysis.
      We determined urinary protein/creatinine ratio as a functional parameter. AGE
      localization was examined by immunohistochemistry using the anti-AGE-RNase
      antibody. RESULTS: Renal collagen-bound AGE were decreased and urinary AGE
      excretion was increased in PTB-treated diabetic mice. However, collagen-released
      CML and pentosidine were similar in both groups. Glomerular histology and
      morphometric analysis revealed also no differences between PTB-and saline-treated
      diabetic mice. The urinary protein/creatinine ratio was unaffected by PTB
      treatment. AGE staining by anti-AGE-RNase antibody was present in Bowman's
      capsules, glomerular basement membranes and cortical tubules. It was decreased in
      all structures in PTB-treated diabetic mice. CONCLUSION: In summary, PTB
      decreased renal AGE accumulation but did not ameliorate glomerular lesions or
      proteinuria. Thus, cleavage of AGE by PTB is not sufficient to prevent
      development of diabetic nephropathy in C57BL/6 mice.

PMID- 11520303
TI  - Effects of chronic treatment with acarbose on glucose and lipid metabolism in
      obese diabetic Wistar rats.
AB  - AIMS: The effect of chronic treatment with acarbose on fasting plasma glucose,
      insulin, triglyceride, cholesterol and free fatty acid (FFA) concentrations, as
      well as on the glucose and insulin excursions during oral glucose tolerance test
      (OGTT), in obese diabetic Wistar (WDF) rats was investigated. METHODS: Forty-five
      mature male WDF rats were randomly distributed to one of the three treatment
      groups (no acarbose, 20 mg and 40 mg of acarbose/100 g of chow, respectively).
      After 3.5, 7.5 and 11.5 months, animals were tested for glucose tolerance by
      means of an OGTT, and their respective metabolic profiles were determined.
      Control determinations were done in obese and age-matched lean animals before the
      start of the trial. RESULTS: The WDF rats exhibit higher body weight and fasting
      blood glucose, insulin, triglyceride and cholesterol concentrations compared to
      lean animals. Moreover, they show marked glucose intolerance as indicated by the
      glucose and insulin excursions during OGTT. Interestingly, in both treated and
      untreated animals, a reversion of the hyperglycaemic state as well as an
      improvement of the glucose tolerance is observed. However, whereas in the group
      receiving no acarbose this is accounted for by dramatic increases in fasting
      plasma insulin concentrations and insulin secretion during OGTT (as indicated by
      the DeltaInsulin area), in rats treated with acarbose the reversion of the
      diabetic state takes place without increments in hormone concentration. In
      addition, rats treated with acarbose for 3.5 and 7.5 months show lower plasma
      triglyceride and FFA concentrations, and the same was observed for cholesterol at
      the highest dosage of the drug. CONCLUSIONS: Chronic treatment with acarbose of
      WDF rats improves the glycaemic and lipidic control as well as the glucose
      tolerance, with a lower demand of pancreatic insulin than in untreated rats. This
      data suggests that the long-term modulation of glucose and insulin excursions
      after meals improves the insulin sensitivity in this rat strain.

PMID- 11520304
TI  - Differences in pharmacotherapy and in glucose control of type 2 diabetes patients
      in two neighbouring towns: a longitudinal population-based study.
AB  - AIM: To compare prescribing, dosage and blood glucose levels in patients with
      type 2 diabetes in two communities with differences in anti-hyperglycaemic drug
      utilization. METHODS: A retrospective longitudinal (1984-1994) population-based
      study in two neighbour towns in southern Sweden. The mean prescribed daily dose
      was expressed as a fraction of the Defined Daily Dose (DDD) for each drug.
      RESULTS: In town A, prescribing of oral agents and insulin was predominantly made
      by one specialized diabetes clinician, while in town B it was spread among
      several different general practitioners and one specialist. Altogether 44 636
      medical visits by 2348 patients were identified. In each town, about 40% of the
      patients were treated without anti-hyperglycaemic drugs, about 40% with oral
      agents and about 20% with insulin. However, there were pronounced between-town
      differences in dosage and glucose control. The mean prescribed daily dose of
      sulphonylurea monotherapy decreased gradually from approximately 0.7 to
      approximately 0.5 DDD in town B but remained approximately 0.8 DDD in town A. The
      proportion of patients on both sulphonylurea and metformin increased
      substantially in town A but not in town B. In these patients, the mean prescribed
      daily dose of sulphonylurea exceeded 1.0 DDD in both towns, although it decreased
      with time in town B. The mean prescribed daily dose of insulin increased from
      1.05 to 1.2 DDD in town A but remained virtually unchanged at 0.95 DDD in town B.
      The mean fasting blood glucose was lower in town A than in town B both overall
      (7.7 vs. 8.8 mmol/l), in those treated without any anti-hyperglycaemic drugs (7.2
      vs. 8.1 mmol/l), in those on sulphonylurea monotherapy (8.3 vs. 9.7 mmol/l) and
      in those treated with insulin (8.1 vs. 10.2 mmol/l). CONCLUSIONS: Glucose control
      in routine care was better when most patients were treated by a diabetes
      specialist and were exposed to more intense pharmacotherapy.

PMID- 11520306
TI  - Anomalous lipoproteins in obese Zucker rats.
AB  - AIMS: Obesity is characterized by dislipoproteinaemia with increased cholesterol
      and triacylglycerol levels and lower chylomicra disposal rates. We studied here
      whether these alterations were related to lipoprotein number and/or size and
      composition. METHODS: Plasma from lean and obese Zucker rats was fractionated
      into lipoprotein classes (chylomicra, very low density lipoprotein (VLDL), low
      density lipoprotein (LDL) and high density lipoprotein (HDL)) by differential
      centrifugation. The apoprotein and lipid composition of each fraction were
      measured. Lipoprotein particle size was estimated by dynamic light scattering and
      used to tabulate the mean diameter and volume of lipoprotein micelles. Particle
      mass was calculated from the density and volume. The mass of lipids and protein
      in each fraction/ml of plasma allowed the estimation of mean particle
      concentration and then the number of molecules of lipid and protein/unit of
      lipoprotein micelle. RESULTS: A large part of hyperlipidaemia of obese rats is
      due to the accumulation of chylomicra: 1.3 +/- 0.2 mg/ml in lean rats [LR] (34%
      of all lipoproteins) and 8.2 +/- 0.9 mg/ml in the obese rats [OR] (66% of all
      lipoproteins). Lipid percentage composition of lipoproteins was similar in both
      groups. The particle size of LDL and HDL was much higher in OR than in LR: LDLs
      weighed 31.1 +/- 7.5 ag (LR) vs. 273 +/- 81 ag (OR), and HDLs weighed 31.7 +/-
      12.6 ag (LR) and 375 +/- 103 ag (OR). In chylomicra and VLDL there was a relative
      scarcity of apoproteins in OR compared with LR. The whole architecture of LDLs is
      altered in OR, with a predominance of surface lipids: phospholipid and free
      cholesterol, and lower amounts of core lipids: triacylglycerols and cholesterol
      esters, with surface/core lipids ratios of 0.74 (LR) and 1.89 (OR). The
      consequences of anomalous LDL and HDL composition, size and overall structure may
      result in magnified lipoprotein metabolism alterations that hamper their ability
      to transfer apolipoproteins to larger chylomicra and VLDL, and to alter
      cholesterol transfer and binding of their apoproteins to cell surface receptors.
      The smaller number of LDL and HDL particles may further compound these
      difficulties and thus change the free to esterified cholesterol ratios observed
      in OR. CONCLUSIONS: The main conclusions of this study are the key importance of
      chylomicron analysis for a better understanding of the transfer of lipids, and
      the altered lipoprotein size and apoprotein distribution in obese rats, which
      seriously hamper cholesterol interchange, resulting in hypercholesterolaemia, and
      thus triggering even more far-reaching consequences for the well-being of the
      obese.

PMID- 11520305
TI  - Reduction of incretin-like salivatin in saliva from patients with type 2 diabetes
      and in parotid glands of streptozotocin-diabetic BALB/c mice.
AB  - AIM: Diabetic xerostomia is a typical syndrome in diabetic complication. We have
      reported that salivatin (salivary peptide P-C) derived from human saliva
      potentiates glucose-stimulated insulin release and inhibits arginine-stimulated
      glucagon release. The present study is aimed to gain further evidence on the
      physiological role by investigating the diabetic state-induced change in the
      amount of salivatin. METHODS: The amount of salivatin was measured in saliva
      taken from patients with type 2 diabetes with ELISA and with rabbit antiserum
      against human salivatin immunocytochemically in sections of parotid glands from
      streptozotocin-diabetic BALB/c mice. RESULTS: The amount of salivatin after a
      meal was reduced by diabetes in both human saliva and in the serous secretory
      granule of mouse parotid gland acinar cells. CONCLUSIONS: The above results
      suggest that salivatin lowers hyperglycaemia after meal and sustains the normal
      blood glucose levels by incretin-like mechanisms. The function may be damaged by
      diabetes, and this in turn might make the diabetes worse.

PMID- 11520307
TI  - Effect of vanadate on glycogen synthesis in dexamethasone-treated 3T3 adipocytes:
      evidence for a novel insulin sensitizing action.
AB  - AIM: Type 2 diabetes is characterized by peripheral tissue insulin resistance.
      The present study was carried out to determine the insulin sensitizing action of
      vanadium using dexamethasone-treated 3T3 adipocytes as an in-vitro model of
      insulin resistance. METHODS: Fully differentiated 3T3 adipocytes were incubated
      with or without 100 nM dexamethasone in the presence or absence of 200 nM insulin
      for 6 days. Sodium orthovanadate (0-1000 microM) was added on day 2 and was
      present during the last 4 days. At the end, insulin (100 nM) stimulated glycogen
      synthesis was determined. RESULTS: Vanadate treatment for 4 days, caused 2-3-fold
      increase in glycogen synthesis in dexamethasone treated adipocytes. At 100
      microM, vanadate completely reversed dexamethasone-induced insulin resistance (by
      increasing the levels from 9.65 +/- 0.80 to 28.4 +/- 4.9 nmol/h). In cells
      treated with dexamethasone and insulin, vanadium was partially active and it
      caused only 30% increase in glycogen synthesis. Exposure of dexamethasone treated
      cells for 24 h with vanadium did not affect glycogen synthesis. Under identical
      condition, vanadium had no significant effect in the normal insulin sensitive
      adipocytes. Vanadium at 100 microM had no effect on 125I-insulin binding to
      insulin-resistant adipocytes. Glycogen synthesis in the normal and insulin
      resistant adipocytes was stimulated by lithium, an inhibitor of glycogen synthase
      kinase 3 beta, suggesting the involvement of phosphorylation events in
      dexamethasone-induced insulin resistance. CONCLUSIONS: Since vanadium was active
      only in the insulin-resistant adipocytes it is likely that vanadium acts by
      relieving dexamethasone actions rather than having independent effects. These
      results provide evidence for the novel insulin sensitizing action of vanadium
      which might be of future clinical relevance.

PMID- 11520308
TI  - Comparative accuracy of cardiovascular risk prediction methods in patients with
      diabetes mellitus.
AB  - OBJECTIVE: To compare the accuracy of cardiovascular risk prediction methods
      based on equations derived from the Framingham Heart Study in a cohort of
      patients with diabetes mellitus. RESEARCH DESIGN AND METHODS: Risk factor data
      was collected prospectively from 906 patients with diabetes mellitus. Absolute
      cardiovascular risks were calculated using the Framingham equation, and estimated
      with the currently available Framingham-based risk tables and charts. The
      sensitivity, specificity, positive and negative predictive values of the tables
      and charts to assess cardiovascular risk were assessed using calculation of risk
      from the full Framingham equation as the reference method. RESULTS: In all, 146
      subjects (16.1%) had calculated 10-year coronary heart disease (CHD) risks > or =
      30%, and 585 (64.6%) had risks > or = 15%. For identification of those at 10-year
      CHD risk > or = 30%, the original Sheffield tables had a sensitivity of 43% (95%
      confidence intervals (CI) 19.9-61.7%) and specificity of 94% (CI 90.8-96.7%).
      Modifications of the Sheffield tables improve sensitivity (95% CI 93.9-97%) but
      reduce specificity (90% CI 85.6-95.7%). The Joint British Guidelines' charts have
      a moderate sensitivity (69.5% CI 51.8-81.9%) and high specificity (99.7% CI 98.9
      100%). For identification of individuals at a 10-year CHD risk > or = 27%, the
      Framingham categorical tables had a sensitivity of 95% (CI 91.6-97.8%), but a
      specificity of only 83% (95% CI 79.1-85.5%). CONCLUSIONS: The Joint British
      charts appear to have the best performance in a cohort of patients with diabetes
      mellitus, however, calculation of CHD/CVD (cardiovascular disease) risks with
      personal or laboratory computers using the full Framingham equation remains the
      most accurate way to assess cardiovascular risk in a primary prevention setting.

PMID- 11520309
TI  - Metabolic and hormonal effects of tacrolimus (FK506) or cyclosporin
      immunosuppression following renal transplantation.
AB  - Twelve renal transplant recipients randomised to receive immunosuppression with
      either tacrolimus (FK506) or cyclosporin underwent oral glucose tolerance tests
      (OGTT) a median of 8 months (range 7-9) after transplantation. Six healthy
      subjects acted as controls. Compared with the controls, both transplant groups
      had significantly elevated fasting (p < 0.05 for both groups) and postprandial (p
      < 0.001 for tacrolimus and p < 0.05 for cyclosporin) blood glucose
      concentrations. Fasting hyperinsulinaemia was observed in both transplant groups
      (p < 0.05) relative to the control subjects. Glucose-stimulated plasma
      immunoreactive insulin concentrations in the tacrolimus-treatment group were
      significantly higher than in the cyclosporin group (p < 0.05) and the controls (p
      < 0.001). Postprandial blood alanine concentrations were also significantly
      elevated in the tacrolimus group compared with both the controls (p < 0.001) and
      cyclosporin-treated patients (p < 0.001). The raised insulin concentrations with
      normal or increased blood glucose concentrations after renal transplantation
      suggests that insulin resistance was more marked in patients receiving tacrolimus
      based immunosuppression.

PMID- 11520310
TI  - Do baseline serum leptin levels predict weight regain after dieting in obese
      women?
AB  - AIM: Weight loss achieved during weight reduction programme is difficult to
      maintain. We investigated the possible role of circulating leptin in failure or
      success in maintaining weight loss. METHODS: Serum leptin levels were measured in
      30 healthy premenopausal obese women before and after 12 weeks of dietary
      intervention and after 5 months of follow-up. RESULTS: After intervention body
      mass index (BMI) decreased from 30.6 to 25.4 kg/m2 (p < 0.01) and leptin levels
      decreased from 16.7 to 7.7 ng/ml (p < 0.01). After 5 months follow-up 12 women
      regained reduced weight and 18 women maintained weight loss. In the regainers
      leptin levels increased again, but remained low in the maintainers. Baseline
      leptin concentrations were lower in the regainers than in the maintainers (12.1
      vs. 21.2 ng/ml, p = 0.04). During intervention leptin levels decreased three
      times more in the maintainers than in the regainers, although weight loss was
      similar in both groups. CONCLUSIONS: This study shows that obese women who regain
      weight after dieting have significantly lower baseline leptin levels than women
      who maintain weight loss. Our results suggest that differences in leptin
      resistance might exist in similarly obese women which could influence the success
      of dieting.

PMID- 11520311
TI  - Fasting glucose and increasing age.

PMID- 11520313
TI  - Do interictal discharges promote or control seizures? Experimental evidence from
      an in vitro model of epileptiform discharge.
AB  - Interictal and ictal discharges are recorded from limbic structures in temporal
      lobe epilepsy patients. In clinical practice, interictal spikes are used to
      localize the epileptogenic area, but they also are assumed to promote ictal
      events. Here I review data obtained from combined slices of mouse hippocampus
      entorhinal cortex that indicate an inverse relation between interictal and ictal
      events. In this preparation, application of 4-aminopyridine or Mg2+-free medium
      induce (a) interictal discharges that originated from CA3 and propagate (via the
      Schaffer collaterals) to CA1 and entorhinal cortex, to return to the hippocampus
      through the dentate area; and (b) ictal discharges that initiate in the
      entorhinal cortex and propagate to the hippocampus via the dentate gyrus.
      Interictal activity occurs throughout the experiment (up to 6 h), whereas ictal
      discharges disappear after 1-2 h. Schaffer collateral cut abolishes interictal
      discharges in CA1, entorhinal cortex, and dentate and reestablishes entorhinal
      ictal discharges. Moreover, ictal discharge generation in the entorhinal cortex
      after Schaffer collateral cut is prevented by mimicking CA3 activity with
      rhythmic electrical stimulation of CA1 outputs. Thus hippocampal interictal
      activity controls the ability of the entorhinal cortex to generate seizures. It
      also may be proposed that Schaffer collateral cut may model the epileptic
      condition in which CA3 damage results in loss of hippocampal control over the
      entorhinal cortex. In conclusion, these experiments demonstrate that interictal
      activity controls rather than promotes ictal events, and functional integrity of
      CA3 constitutes a critical control mechanism in temporal lobe epilepsy.

PMID- 11520314
TI  - Cell death and synaptic reorganizations produced by seizures.
AB  - The events that follow epilepsy seizures are not restricted to the immediate
      period. A series of long-term alterations occurs, including synaptic
      rearrangements, which have an impact on the brain circuit's mode of operation.
      With models of temporal lobe epilepsy, seizures have been shown to generate long
      lasting changes in synaptic efficacy (epileptic long-term potentiation) because
      of removal of the magnesium block, activation of N-methyl-D-aspartate receptors,
      and an increase in intracellular calcium. This novel form of synaptic plasticity
      provides a link between memory effects and pathologic processes. Additionally,
      high-affinity kainate autoradiography, Timm stain, intraventricular injection of
      kainic acid, and 3D reconstruction experiments clearly indicate that even brief
      seizures produce changes in synaptic efficacy, followed 2-3 weeks later by
      aberrant neosynapse formation. Several key steps have been identified in the
      cascade leading from transient hyperactivity episodes to long-lasting, quasi
      permanent modification of the neuronal circuit organization. These include the
      activation of immediate-early genes, activation of growth factor genes within
      hours, alterations in glutamate receptors, glial hypertrophy, and cytoskeletal
      protein changes. The cascade is activated by the increase in intracellular
      calcium and leads to axonal growth and neosynapse formation, which in turn
      participates in the etiology of the syndrome by reducing the threshold for
      further seizures. In summary, study data imply that the mature epileptic circuit
      has unique features in comparison with those present before a seizure episode,
      including new receptors, ionic channels, and other proteins. It is therefore
      essential to develop novel strategies based on the unique mode of operation of
      the mature epileptic circuit, rather than on acute models of epilepsy.

PMID- 11520315
TI  - GABAergic mechanisms in epilepsy.
AB  - gamma-Aminobutyric acid (GABA), the principal inhibitory neurotransmitter in the
      cerebral cortex, maintains the inhibitory tone that counterbalances neuronal
      excitation. When this balance is perturbed, seizures may ensue. GABA is formed
      within GABAergic axon terminals and released into the synapse, where it acts at
      one of two types of receptor: GABAA, which controls chloride entry into the cell,
      and GABAB, which increases potassium conductance, decreases calcium entry, and
      inhibits the presynaptic release of other transmitters. GABAA-receptor binding
      influences the early portion of the GABA-mediated inhibitory postsynaptic
      potential, whereas GABAB binding influences the late portion. GABA is rapidly
      removed by uptake into both glia and presynaptic nerve terminals and then
      catabolized by GABA transaminase. Experimental and clinical study evidence
      indicates that GABA has an important role in the mechanism and treatment of
      epilepsy: (a) Abnormalities of GABAergic function have been observed in genetic
      and acquired animal models of epilepsy; (b) Reductions of GABA-mediated
      inhibition, activity of glutamate decarboxylase, binding to GABAA and
      benzodiazepine sites, GABA in cerebrospinal fluid and brain tissue, and GABA
      detected during microdialysis studies have been reported in studies of human
      epileptic brain tissue; (c) GABA agonists suppress seizures, and GABA antagonists
      produce seizures; (d) Drugs that inhibit GABA synthesis cause seizures; and (e)
      Benzodiazepines and barbiturates work by enhancing GABA-mediated inhibition.
      Finally, drugs that increase synaptic GABA are potent anticonvulsants. Two
      recently developed antiepileptic drugs (AEDs), vigabatrin (VGB) and tiagabine
      (TGB), are examples of such agents. However, their mechanisms of action are quite
      different (VGB is an irreversible suicide inhibitor of GABA transaminase, whereas
      TGB blocks GABA reuptake into neurons and glia), which may account for observed
      differences in drug side-effect profile.

PMID- 11520316
TI  - Involvement of the thalamocortical system in epileptic loss of consciousness.
AB  - Experiments on putative neuronal mechanisms underlying absence seizures as well
      as clinical observations are critically reviewed for their ability to explain
      apparent "loss of consciousness." It is argued that the initial defect in
      absences lies with corticothalamic (CT) neuronal mechanisms responsible for
      selective attention and/or planning for action, rather than with those
      establishing either the states or the contents of consciousness. Normally, rich
      thalamocortical (TC)-CT feedback loops regulate the flow of information to the
      cortex and help its neurons to organize themselves in discrete assemblies, which
      through high-frequency (>30 Hz) oscillations bind those distributed processes of
      the brain that are considered important, so that we are able to focus on what is
      needed from moment to moment and be aware of this fact. This ability is
      transiently lost in absence seizures, because large numbers of CT loops are
      recruited for seconds in much stronger, low-frequency ( approximately 3 Hz)
      oscillations of EPSP/IPSP sequences, which underlie electroencephalographic (EEG)
      spike-and-wave discharges (SWDs). These oscillations probably result from a
      transformation of the normal EEG rhythm of sleep spindles on an abnormal increase
      of cortical excitability that results in strong activation of inhibitory neurons
      in the cortex and in nucleus reticularis thalami. The strong general enhancement
      of CT feedback during SWDs may disallow the discrete feedback, which normally
      selects specific TC circuits for conscious perception and/or motor reaction. Such
      a mechanism of SWD generation allows variability in the extent to which different
      TC sectors are engaged in the SWD activity and thus explains the variable ability
      of some patients to respond during an absence, depending on the sensory modality
      examined.

PMID- 11520317
TI  - Interactions between hormones and epilepsy in female patients.
AB  - Epilepsy and epileptic seizures may influence the release of hormones from the
      hypothalamus and the pituitary. After complex-partial seizures or generalized
      tonic-clonic seizures, serum prolactin increases in about two thirds of cases.
      Apart from this transient effect, interictal epileptic discharges from the
      temporal lobe may exert a prolonged influence on hormone release. Changes in
      luteinizing hormone (LH) pulse frequency and increased prolactin levels have been
      reported. As a consequence, menstrual cycles may be disturbed. The cyclic change
      of sex serum hormones during the ovulatory menstrual cycle may have an impact on
      seizure occurrence during the days of ovulation and/or menstruation (e.g.,
      catamenial seizures). By a supplementation of progesterone during the second half
      of anovulatory cycles, a decrease of seizure frequency can be achieved.

PMID- 11520318
TI  - Epileptic encephalopathy.
AB  - Epileptic encephalopathies are conditions in which neurologic deterioration
      results mainly from epileptic activity. It can be due to very frequent or severe
      seizures, or to subcontinuous paroxysmal interictal activity. The former consists
      mainly of severe myoclonic epilepsy in infancy (SMEN), in which patients exhibit
      seizures from the middle of the first year of life with repeated episodes of
      status epilepticus, and migrating partial epilepsy in infancy, in which, from the
      first trimester of life, partial seizures affect various areas of the cortex
      randomly and in a subcontinuous fashion. Cases with subcontinuous paroxysmal
      interictal activity affect newborns with suppression bursts, thus consisting of
      either Ohtahara syndrome or neonatal myoclonic encephalopathy, and infants with
      infantile spasms (IS), although rare cases do not start until age 4 years. In
      childhood, it consists of various types of generalized seizures combined with
      either slow spike-waves of the Lennox-Gastaut syndrome (LGS) or with myoclonus
      and 3-Hz spike-waves of myoclonic-astatic epilepsy, and continuous spike-waves in
      slow sleep (CSWS) combined with various neuropsychological patterns including
      Landau-Kleffner syndrome, frontal lobe syndrome, orofacial dyspraxia, or negative
      myoclonus. Management differs for all these syndromes, with the combination of
      clobazam (CLB) and stiripentol (STP) being promising for SMEN, vigabatrin (VGB)
      for IS, lamotrigine (LTG) for LGS, and steroids for CSWS. It is important to
      avoid potential drug-induced worsening by phenobarbital (PB), phenytoin (PHT),
      carbamazepine (CBZ), tiagabine (TGB), and VGB; in children and especially in
      infants, treatment with valproate is preferred each time the proper diagnosis is
      not reached.

PMID- 11520319
TI  - Management strategies for refractory localization-related seizures.
AB  - Localization-related epilepsy, the most common type of seizure disorder, often
      provides major management problems. Five new antiepileptic drugs (AEDs) with
      different mechanisms of action have been licensed in the United Kingdom in the
      1990s for adjunctive use in the management of poorly controlled partial seizures.
      These were, in chronologic order, vigabatrin, lamotrigine, gabapentin,
      topiramate, and tiagabine. Their practical deployment is explored here. Mention
      also is made of clobazam and acetazolamide. Combination therapy with two or even
      three AEDs having complementary pharmacologic effects can provide an essential
      contribution to the management of partial seizures. This article discusses some
      of the pharmacologic strategies used in treating patients with refractory
      localization-related epilepsy.

PMID- 11520320
TI  - The management of refractory idiopathic epilepsies.
AB  - Idiopathic epilepsies comprise a wide variety of partial and generalized
      syndromes that have in common a known or presumed genetic etiology and the lack
      of overt abnormalities other than the epilepsy itself. Most of these epilepsies
      have a benign natural history and/or show a favorable response to antiepileptic
      drug (AED) therapy, but pharmacoresistance does occur in some patients. In
      general, therapeutic algorithms in idiopathic partial epilepsies (IPEs) are
      similar to those used for symptomatic partial epilepsies, but aggressive
      pharmacologic therapy is rarely indicated in these patients. In self-limited
      conditions such as benign epilepsy of childhood with centrotemporal spikes or
      some forms of benign epilepsy with occipital paroxysms, AED treatment may not
      even be indicated unless seizures interfere significantly with quality of life.
      Valproate (VPA) is usually regarded as the drug of choice in idiopathic
      generalized epilepsies (IGEs). Most patients become rapidly seizure free, and
      poor compliance or prescription of an inappropriate AED because of misdiagnosis
      are the most common causes of treatment failure in IGEs. In those patients who
      did not respond well to VPA (or in whom VPA is considered contraindicated), the
      choice of alternative AEDs is guided by syndromic diagnosis and associated
      possible coexistence of multiple seizure types. Lamotrigine is establishing
      itself as a useful agent for many refractory IGEs, and might be considered for
      first-line use in selected patients. Topiramate (TPM) is another promising new
      agent in the management of refractory tonic-clonic seizures of nonfocal onset,
      but its potential efficacy against other primarily generalized seizure types has
      not been clearly established. Some of the older drugs, particularly ethosuximide
      (ESM), barbiturates, and benzodiazepines (BZDs), still have an important role in
      the management of refractory IGEs, especially in combination with VPA. Because
      carbamazepine (CBZ), phenytoin (PHT), tiagabine (TGB), vigabatrin (VGB), and
      gabapentin (GBP) may precipitate or aggravate absence and/or myoclonic jerks,
      their role in IGE syndromes associated with multiple seizure types is limited
      mostly to adjunctive use in patients unresponsive to first-line therapy.

PMID- 11520321
TI  - Idiopathic epilepsy and paroxysmal dyskinesia.
AB  - Although some motor manifestations of epilepsy and of paroxysmal dyskinesia may
      be difficult to differentiate clinically, the current understanding is that the
      two disorders are clinically distinct. However, there are several recent reports
      of families in which different individuals had either disorder or both
      manifestations, with age-related expression. Co-occurrence makes it likely that a
      common, genetically determined, pathophysiologic abnormality is variably
      expressed in the cerebral cortex and in basal ganglia. A rather homogeneous
      syndrome of autosomal dominant infantile convulsions and paroxysmal (dystonic)
      choreoathetosis (ICCA) was described in six families from France, China and
      Japan. Linkage analysis in the French and Chinese families allowed the mapping of
      the disease gene in a 10-cM interval within the pericentromeric region of
      chromosome 16. An Italian pedigree in which three members in the same generation
      were affected by rolandic epilepsy, paroxysmal exercise-induced dystonia (PED),
      and writer's cramp was subsequently reported. Linkage analysis showed a common
      homozygous haplotype in a critical region spanning 6 cM and entirely included
      within the ICCA critical region. Clinical analogies and linkage findings suggest
      that the same gene could be responsible for rolandic epilepsy, PED, writer's
      cramp (WC), and ICCA, with specific mutations accounting for each of these
      mendelian disorders. Evidence for a major gene or a cluster of genes for epilepsy
      and paroxysmal dyskinesia to the pericentromeric region of chromosome 16 is
      reinforced by the recent linkage of a family with autosomal dominant paroxysmal
      dyskinesia to a critical region partially overlapping with ICCA and contiguous to
      the RE-PED-WC regions. Additional autosomal dominant pedigrees are on record,
      from Australia and Italy, in which epilepsy was variably associated with
      paroxysmal kinesigenic or exercise-induced dystonia. Ion channel genes are
      potentially interesting candidates for syndromes featuring both these paroxysmal
      neurologic disorders. Increased awareness of their possible co-occurrence will
      certainly increase the number of observations in the next few years.

PMID- 11520322
TI  - Tiagabine in clinical practice.
AB  - Among the newly introduced antiepileptic drugs (AEDs), tiagabine (TGB) stands out
      as a compound with a well-understood and documented mechanism of action. It is a
      lipophilic derivative of nipecotic acid that blocks gamma-aminobutyric acid
      (GABA) reuptake by inhibition of the GAT-1 transportation system, and that has no
      other significant pharmacodynamic effect. The relationship between intake and
      blood levels is linear. Usual daily maintenance doses range from 20 to 50 mg. It
      is completely absorbed by the gastrointestinal tract, and its half-life is
      approximately 7-9 h. TGB is sensitive to enzyme induction: when coprescribed with
      enzyme-inducing AEDs, its half-life is shortened to 2-3 h, whereas the daily
      dosage has to be increased into the upper range. It should be given 3 times per
      day. Placebo-controlled, double-blind, add-on studies conducted in patients with
      drug-resistant focal epilepsies have demonstrated its efficacy and overall
      safety. The clinical benefits appear to persist over time. Data on its use in
      monotherapy are scanty. The efficacy and tolerability of TGB in the pediatric age
      still remain to be investigated adequately. In daily practice, TGB appears to be
      a safe drug, but mild to moderate side effects are frequently seen, especially
      during titration: these include dizziness and fatigue, and are clearly abated
      when the drug is absorbed during meals. Titration should be especially slow, no
      faster than 5 mg weekly. Clinicians also should beware of the possible occurrence
      of confusion, which may be misdiagnosed as absence status, a short-lasting,
      quickly reversible central nervous system-related side effect that appears to be
      correlated with the peak plasma concentrations of TGB. Particularly beneficial
      indications for TGB and/or AED associations including TGB have not been pointed
      out, but there is a hint that it works best in temporal lobe epilepsies.

PMID- 11520323
TI  - Long-term safety of tiagabine.
AB  - Tiagabine (TGB) is now registered in >20 countries, and the total number of
      treated patients approaches 90,000. Short-term safety data were derived mainly
      from five placebo-controlled, add-on studies in adults with therapy-resistant
      partial epilepsy, and two conversion to TGB monotherapy studies. Central nervous
      system (CNS)-related adverse effects, most frequently dizziness, were common with
      TGB treatment during the titration period; the risk became similar to placebo
      rates during fixed-dose periods. Other adverse events that were more frequent in
      TGB- than in placebo-treated patients were asthenia, nervousness, tremor,
      concentration difficulties, depressive mood, and language problems. TGB doses
      should be titrated slowly and taken with food to avoid rapid increases in plasma
      concentrations, thus minimizing the risks of adverse events. Overall, >2,500
      patients have been exposed to TGB during clinical trials, with 1,274 patients
      treated >12 months, the majority of whom received TGB 24-60 mg/day. No
      idiosyncratic reactions have been linked to the use of TGB, and no abnormalities
      in hematology or common chemistry values were reported. In all the epilepsy
      studies combined, 21% of patients discontinued treatment because of adverse
      events, usually during the first 6 months of treatment. No adverse effects on
      cognitive abilities were detected when the neuropsychological effects of TGB add
      on therapy and monotherapy were evaluated. TGB does not appear to cause an excess
      risk of psychosis or increase the incidence of status epilepticus or spike/wave
      discharges. No evidence of a relationship between visual field constriction and
      TGB treatment was found in a study of 15 patients converted to TGB monotherapy
      (mean dose, 22 mg/day; mean duration, 2.5 years) who had a full ophthalmologic
      evaluation. In conclusion, the characteristics of TGB in the management of
      partial epilepsy are enhanced by its favorable side-effect profile in the
      cognitive area.

PMID- 11520324
TI  - Tiagabine (gabitril) experience in children.
AB  - Tiagabine (TGB) is indicated as adjunctive therapy for partial seizures in adults
      and children aged 12 years and older. Double-blind, placebo-controlled studies of
      TGB treatment are under way in younger children with various forms of epilepsy.
      The results of pediatric pharmacokinetic trials indicate patterns similar to
      those seen in adults. An open-label study was conducted in the United States in
      31 children with refractory complex partial seizures, with doses escalated every
      2 weeks by 0.25 mg/kg up to a maximal daily dose of 1 mg/kg. Twenty-nine patients
      were treated with TGB for >1 year; 26 completed the study, of whom 18 were
      receiving monotherapy at study completion. A European dose-escalation study
      evaluated TGB (0.25-1.5 mg/kg/day) as add-on therapy in 52 children aged 2-15
      years. TGB appeared to be more effective in localization-related epilepsy
      syndromes, with 17 of 23 patients with localization-related epilepsy having a 33%
      median reduction of seizure rate compared with baseline in the fourth month of
      treatment, and six patients having > or =50% seizure rate reduction. In this
      study, myoclonic seizures and spasms showed a poor response as opposed to
      encouraging findings reported by other groups with these seizure types. The
      adverse effect profile of TGB in children with epilepsy is similar to that in
      adults. In the U.S. study, most common adverse events were related to the central
      nervous system (CNS) and decreased over time. In the European study, mostly mild
      to moderate adverse events, including asthenia (19%), nervousness (19%),
      dizziness (17%), and somnolence (17%), were reported by 83% of TGB-treated
      children (39% of children reported adverse events during the single-blind placebo
      period). In summary, preliminary pediatric data with TGB suggest particular
      efficacy against epilepsy characterized by partial seizures or other syndromes,
      and further investigation is warranted.

PMID- 11520325
TI  - Epilepsy in the elderly: the use of tiagabine.
AB  - The incidence of epilepsy increases sharply in patients older than 60 years.
      There is a clear need for clinical trials designed specifically for this age
      group, as elderly patients differ from younger patients with epilepsy with
      respect to seizure etiology, coexisting diseases, concomitant drug therapy, and
      drug disposition. The new antiepileptic drugs (AEDs) are often associated with
      fewer side effects than are the traditional AEDs and may be particularly useful
      in the elderly. The pharmacokinetics of tiagabine (TGB) are not significantly
      modified in elderly patients, although elimination is more rapid in the presence
      of enzyme-inducing AEDs. Efficacy and tolerability data on TGB in elderly
      patients is currently limited, and a formal trial of TGB monotherapy in this age
      group is needed.

PMID- 11520326
TI  - Epilepsy in the elderly: some clinical and pharmacotherapeutic aspects.
AB  - The majority of epileptic seizures and epilepsies are no longer manifested in
      childhood and adolescence; instead their incidence is higher at the age of 65
      years or older than during the first two decades of life. After cerebrovascular
      disorders and dementias, epileptic seizures and epilepsies now constitute the
      third most frequent neurologic problem encountered in the elderly. Important
      clinical features of epilepsy in the elderly related to the diagnosis include the
      most common seizure types and causes. Special features of drug treatment for
      epilepsy in the elderly result not only from the physiologic changes in the
      elderly but also from the particular pharmacology of the respective drugs.
      Because elderly patients very often require other long-term medication in
      addition to antiepileptic therapy, drug interactions between different
      antiepileptic drugs and between antiepileptics and other drugs can be of major
      significance. Other special features of pharmacotherapy for epilepsy in the
      elderly include the presence of liver and kidney diseases.

PMID- 11520327
TI  - Polycystic ovarian syndrome in women with epilepsy: a review.
AB  - Polycystic ovarian syndrome (PCOS) remains a controversial issue in women with
      epilepsy. The syndrome is characterized by clinical signs of endocrine
      dysfunction, such as irregular menstruation, hirsutism, and infertility, but its
      pathogenesis and presentation are heterogeneous. There are few data on the
      relationship between epilepsy and PCOS. Studies by a Finnish group have raised
      the issue of an association between valproate (VPA) and PCOS in young women with
      epilepsy. These studies, however, were retrospective, laid emphasis on polycystic
      ovary morphology rather than on clinical endocrine dysfunction, and were
      undertaken in selected populations. Further studies, both in Italy and Germany,
      failed to replicate the findings of the Finnish group. Future research should
      ideally be prospective and include baseline data in untreated women. No
      compelling data lead to a specific contraindication of the use of VPA in young
      women, and the drug remains a first-line treatment option.

PMID- 11520328
TI  - Assessment of quality of life in people with epilepsy: some practical
      implications.
AB  - Growing recognition of the need to assess the impact of epilepsy on psychosocial
      functioning has led to a number of initiatives to quantify quality of life (QOL)
      in patients with this condition. To understand the impact of epilepsy and its
      treatment, physical, social, neuropsychological, and psychological functioning
      aspects must be considered. It also is apparent from previous research work that
      measures of QOL should be comprehensive enough to address the question under
      consideration, but also simple and as brief as possible. A number of QOL measures
      for assessing the impact of epilepsy and its treatment exist, such as the
      Washington Psychosocial Seizure Inventory, the Social Effects Scale, the Epilepsy
      Surgery Inventory, the Quality of Life in Epilepsy (QOLIE) questionnaire, and the
      Liverpool QOL Battery. These measures have in most cases been shown to be
      reliable, valid, and sensitive to change, although at the current stage of
      development, some are better validated than others. It is generally agreed that
      the best approach is to use a standard generic instrument with disease-specific
      additions. Selection of a measure already in existence is recommended, as the
      process of producing a new measure is costly in terms of both resources and time.
      Some consideration also needs to be given to factors such as the process of
      administration (e.g., self-completion or administration at interview) or the
      timing of data collection. Then questions such as the cross-cultural
      applicability of QOL measures and the real relevance of the changes remain to be
      answered. It is hoped that, over the next few years, significant progress will be
      made in addressing these issues.

PMID- 11520330
TI  - MOSES: an educational program for patients with epilepsy and their relatives.
AB  - The knowledge of patients with epilepsy about their own condition is poor, and
      thus the need for educational programs for people with epilepsy has long been
      recognized. However, no such programs have been established in their routine
      care. The Modular Service Package Epilepsy (MOSES) now tries to fill this gap for
      patients in German-speaking countries. The program was developed by a
      multidisciplinary group (neurologists, nonmedical professional helpers, and
      representatives of national epilepsy associations) for people with epilepsy older
      than 16 years, independent of the kind and severity of their epilepsy. MOSES is
      designed for group education and can be used in inpatient and outpatient settings
      in epilepsy centers, in clinics, and by neurologists in private practice. The
      program aims to help patients achieve a better understanding of their disease, to
      gain more self-confidence, and to take over responsibility, thus supporting
      patients to become experts in managing their own illness. Being modular in
      structure, MOSES includes nine units: living with epilepsy, epidemiology, basic
      knowledge, diagnostics, therapy, self-control, prognosis, psychosocial aspects,
      and network epilepsy. MOSES consists of a workout manual for patients and a
      trainer manual. For potential trainers, special "train-the-trainer seminars" are
      offered and considered mandatory. About 400 patients have participated in a MOSES
      training program in Germany, Switzerland, and Austria. The efficacy of the
      program is currently been evaluated.

PMID- 11520329
TI  - The short-term impact of adjunctive tiagabine on health-related quality of life.
AB  - Combinations of tiagabine (TGB), carbamazepine (CBZ), and phenytoin (PHT) were
      compared for their impact on health-related quality of life (HRQOL) and adverse
      effects related to treatment efficacy for people with frequent complex partial
      seizures. Two independent, randomized, double-blind clinical trials for efficacy
      and safety were conducted simultaneously with treatment groups: CBZ+PHT versus
      CBZ+TGB, and PHT+CBZ versus PHT+TGB. Treatment was initiated at week 0 and
      continued through week 16. HRQOL was evaluated with the QOLIE-89. Treatment
      success was defined as > or =50% reduction in complex partial seizures. Among
      patients who achieved a > or =50% reduction in seizures, addition of TGB to
      baseline PHT enhanced patient perceptions of attention/concentration (13%; p =
      0.002), memory (17%; p = 0.042), and language subscales (22%; p = 0.004).
      Addition of CBZ to PHT led to positive change in the work/driving/social
      relations subscale (14%; p = 0.004). These improvements were significantly
      different only between visits, not between the two treatment groups. Seizure
      worry subscale scores showed improvement among all treatment groups and was
      probably related to participation in the clinical trial. These exploratory
      analyses suggest a possible early positive effect of TGB on patient-perceived
      cognitive domains using the QOLIE-89. These findings are limited by the small
      sample size and could be related to reduction in seizures.

PMID- 11520331
TI  - Computer assisted learning. A review.
AB  - Since 1980 the amount of medical information has doubled approximately every
      second year. This implies that oral health students as well as professionals need
      to manage the flow of information rationally, in order to learn how to undertake
      evidence-based decision-making for diagnosis and treatment in a given patient
      situation. Current research indicates that computer connected databases and
      computer assisted learning (CAL) may enhance learning and provide the clinician
      with information for decision-making when treating patients. Multimedia for CAL,
      which combines audio and visual data in an interactive form, has proved to be an
      effective tool in education. CAL may supplement and reinforce more traditional
      learning and create opportunities to illustrate clinical situations in an
      interactive way. CAL has the potential to help students develop skills and
      knowledge. Students, staff and professionals consider CAL stimulating and
      motivating. Students easily adapt to CAL although their current computer literacy
      is still low. New authoring tools make it easier for faculties to develop their
      own CAL software. In the future we will see more sophisticated software with
      virtual patients who can communicate and interact with the student in a very
      realistic way. The software will even "step out" from the screen and help the
      student with clinical procedures. However, at present CAL should not replace
      traditional education, but rather be used more as a supplement and for self
      directed studies.

PMID- 11520332
TI  - Computing facilities available to final-year students at 3 UK dental schools in
      1997/8: their use, and students' attitudes to information technology.
AB  - OBJECTIVE: To identify computer facilities available in 3 dental schools where 3
      different approaches to the use of technology-based learning material have been
      adopted and assess dental students' perception of their own computer skills and
      their attitudes towards information technology. DESIGN: Multicentre cross
      sectional by questionnaire. SUBJECTS: All 181 dental students in their final year
      of study (1997-8). RESULTS: The overall participation rate was 80%. There were no
      differences between schools in the students' self assessment of their IT skills
      but only 1/3 regarded themselves as competent in basic skills and nearly 50% of
      students in all 3 schools felt that insufficient IT training had been provided to
      enable them to follow their course without difficulty. There were significant
      differences between schools in most of the other areas examined which reflect the
      different ways in which IT can be used to support the dental course. CONCLUSIONS:
      1. Students value IT as an educational tool. 2. Their awareness of the relevance
      of a knowledge of information technology for their future careers remains
      generally low. 3. There is a need to provide effective instruction in IT skills
      for those dental students who do not acquire these during secondary education.

PMID- 11520333
TI  - The use of group participation and an enquiry-based study guide with computer
      assisted learning.
AB  - The aim of this investigation was to explore the use of group participation and
      an enquiry-based study guide to enhance the learning experience when using a
      computer assisted learning (CAL) program. MATERIALS AND METHODS: Forty-eight
      students were asked to complete a CAL program on resin bonded bridges in groups
      of 2-4 with an enquiry-based study guide. An evaluation questionnaire of the
      learning experience was included with the study guide with paired positive and
      negative questions and open-ended questions for students to complete and return.
      The responses were collated and the nature of the comments qualitatively
      analysed. RESULTS: Thirty-two questionnaires were returned. There were almost
      three times the numbers of positive to negative responses relating to the
      usefulness of the enquiry based study guide, group participation and the CAL
      program. The majority of these positive responses related to the usefulness of
      the study guide and group participation in highlighting and guiding learning and
      creating opportunities for discussion, problem solving and peer teaching. A small
      number of negative responses cited the target-orientated nature of the study
      guide and the longer time needed for group work, due to the varying learning
      abilities of the participants and the need for discussion. CONCLUSION: The use of
      group participation and an enquiry-based study guide was reported to enhance the
      learning experience of CAL.

PMID- 11520334
TI  - A study of videoconferencing for postgraduate continuing education in dentistry
      in the UK--the teachers' view.
AB  - Videoconferencing is an established method for providing medical education over
      long distances. Our aims were to assess the feasibility of videoconferencing in
      dental postgraduate education, to evaluate its practicability, teacher
      satisfaction and evaluate equipment. Twenty-seven teachers from the 4 London
      Dental Schools provided 41 postgraduate dental education sessions on a range of
      topics to regional postgraduate centres and dental practices as part of the
      Thames Health Region's programme. Videoconferencing was carried out using a
      relatively inexpensive personal computer system link using ISDN2 telephone lines
      and Z350 protocol. Presenter views and assessment were obtained by questionnaire,
      interview and videotape. Teachers felt that minimal additional preparation time
      was required for videoconferencing and 21/27 preferred it to in-person teaching,
      most noting the saving in travel time. Only 3 of the teachers were dissatisfied
      with their ability to communicate, 4 were equivocal and 20 were either pleased or
      very pleased. The teachers largely enjoyed the experience and performed well in
      the new medium. However, sound quality proved inadequate in 5/41 links and most
      sessions included some periods of suboptimal sound. Only 4 teachers were
      satisfied with their ability to perform question and answer interaction with the
      audience. We conclude that experienced teachers adapt readily to
      videoconferencing and learn to communicate effectively very quickly. Teachers
      were positive about the medium despite its shortcomings and improvements in sound
      quality would allow a rapid expansion of postgraduate dental education by
      videoconference.

PMID- 11520335
TI  - Assessment of a preclinical training system with indirect vision for dental
      education.
AB  - The aim of the present study is the evaluation of a pre-clinical training system
      using indirect vision for dental education purposes. The study population was
      undergraduate dental students between the ages of 18-20, at the beginning of
      their first dental course. From a total of 105 students, those presenting some
      condition that would have had influence on their manual skills and those who for
      some circumstance left the study after beginning it were excluded, resulting in
      69 students (51 female and 18 male) taking part in the study. The study design
      involved two sessions separated by a 7-day interval in which the students used a
      reflection box to develop psychomotor skills in mirror use. In every session they
      performed an initial evaluation test, some training exercises and a final
      evaluation test. The evaluation tests and the training exercises consisted in
      following a curved, straight or convoluted shape in the reflection box. Four
      groups of students were used who trained in different ways using curved or
      straight lines. Evaluation of the tests was based on the number of errors made
      and the time to completion. All students showed an improvement in their
      performance of following curved and straight lines with indirect vision after
      this form of training. The results after the first training session were
      statistically significant, while the further improvement was not significant
      after the 2nd training session. Those students who trained first with curved
      lines and later with straight lines produced more errors than the other groups.
      Female students performed better than male students in this assessment.

PMID- 11520336
TI  - Characteristics and study motivation of Danish dental students in a longitudinal
      perspective.
AB  - This survey encompasses 3 comparable datasets of newly admitted dental students
      in 1972 (n=236), 1982 (n=197), and 1994 (n=108). The objectives of the survey
      were to describe selected socio-demographic characteristics of dental students
      and to analyze possible changes over time as well as possible changes in the
      reasons reported by the students for choosing dentistry as a career, their
      motivations and their expectations concerning the study and the profession of
      dentistry. The results showed that the ratio of women to men remained unchanged
      at 6:4 in all 3 cohorts of students and that the students were increasingly
      recruited from the 2 upper social classes. The motives for choosing dentistry
      mainly included altruistic motives, the desire for varied work with the
      opportunity to put theory into practice, economic rewards, and the implicit
      social status. Compared to the 1972 students, those in 1994 placed greater
      emphasis on social status as a motive, on the opportunity to work in the
      biological and scientific field, and on the ready availability of work outside
      Denmark. The students in all 3 years had strong altruistic motives for choosing
      dentistry, and it would seem that this stable continuity in the cohort of dental
      students would ensure the continuous controlled development of dentistry in the
      new millennium.

PMID- 11520337
TI  - Curriculum guidelines for orofacial pain and temporomandibular disorders.
      European Academy of Craniomandibular Disorders.

PMID- 11520338
TI  - A model of the evolution of the unusual sex chromosome system of Microtus
      oregoni.
AB  - In the creeping vole, Microtus oregoni, females are X0 and males are XY. In the
      female germ line, mitotic nondisjunction ensures that the products of meiosis all
      carry the X chromosome. Similarly, mitotic nondisjunction in the male germ line
      leads to the production of 0 and Y sperm. We propose that the present situation
      in M. oregoni has evolved by invasion of a normal XX/XY system by a mutant X
      chromosome, X', with a complete transmission advantage in X'X females, and a
      complete transmission disadvantage in X'Y males. X' is at best initially nearly
      neutral, but can gain a transmission advantage if it reaches a high enough
      frequency. This is due to the production of X0 females in matings between XX
      females and X'Y males; low fertility and embryo loss of such females reduce the
      fitness of the X chromosome in females, relative to that of X'. Under some
      conditions, however, the enhanced reproductive value of males, caused by the
      production of inviable Y0 embryos in X0 x X'Y matings, can outweigh any advantage
      to X'. Inbreeding also reduces any advantage to X'.

PMID- 11520339
TI  - Genetic differentiation of Baetis alpinus Pictet (Ephemeroptera: Baetidae) in
      fragmented alpine streams.
AB  - The interpretation of low FST values as evidence of high levels of gene flow
      among habitat fragments may be confounded by population genetic structures that
      are indicative of historical rather than present-day levels of gene flow. We
      examined the genetic structure of 23 populations of Baetis alpinus (Insecta:
      Ephemeroptera) living in alpine streams fragmented by lakes ( approximately 10
      000 years old), reservoirs ( approximately 100 years old), and in nonfragmented
      streams, to examine if lakes act as barriers to gene flow and to investigate the
      temporal resolution of allozyme markers. Estimates of gene flow indicated little
      or no genetic divergence along four nonfragmented reference streams and across
      two lakes and two reservoirs (FST=0.004-0.041), but marked differentiation across
      four lakes (FST=0.092-0.362) and across one reservoir that was a lake enlarged by
      a dam (FST=0.075). Differentiation was unrelated to distance between fragments,
      but occurred only in lakes found in valleys that have been ice-free throughout
      the Holocene. We suggest that standing water bodies act as barriers to gene flow
      in B. alpinus and that low FST values observed between fragments separated by
      reservoirs do not indicate high levels of gene flow but rather show that genetic
      differentiation was not detectable within the first 100-1000 years of habitat
      fragmentation.

PMID- 11520340
TI  - The threshold model as a general purpose normalizing transformation.
AB  - The estimation of heritabilities and genetic correlations is based on the
      assumption that the trait distributions are normal. When the distributions are
      not normal it is advisable to transform the data to produce normality. However,
      it is possible that no suitable transformation can be found. The purpose of the
      present paper is to point out that the threshold model of quantitative genetics
      can be used as a generalized transformation. To utilize this method it is only
      necessary to divide the data at the median (approximately) and code the two
      halves as 0 and 1. Estimates can then be made using algorithms outlined herein. A
      simulation study shows that the threshold transformation gave unbiased estimates
      of the heritability and genetic correlation in all cases. The 95% confidence
      limits correctly included the true heritability value in the required 95% of
      cases, while the estimated confidence region for the genetic correlation was also
      correct provided that the geometric mean heritability was greater than
      approximately 0.15, a restriction that applied also to the normally distributed
      data. Confidence intervals estimated from the non-normal data were consistently
      too small. The method is illustrated using data on the proportion of diapausing
      eggs produced by the cricket, Allonemobius socius.

PMID- 11520341
TI  - Development and characterization of DNA sequence OmyP9 associated with the sex
      chromosomes in rainbow trout.
AB  - This work describes the construction and characterization of a sequence
      characterized amplified DNA region (SCAR DNA), designated OmyP9, that was derived
      from a RAPD marker associated with the sex chromosomes in rainbow trout. A RsaI
      restriction fragment length polymorphism in OmyP9 identifies variants A, B and C.
      We found six OmyP9 variant phenotypes - A, B, C, AB, BC and ABC, in 186
      individuals of seven different rainbow trout strains. The patterns of inheritance
      of OmyP9 in 139 fingerlings from 10 crosses of three strains of rainbow trout
      were studied. The males had a greater representation of the A variant (93.3%)
      suggesting an association with the Y chromosome. All male fingerlings analysed
      inherited the A variant from their male parents. These results support the
      hypothesis that OmyP9 is located on the sex chromosomes of rainbow trout, and
      that for the males studied the A variant is located on the Y chromosome in a
      region close to sex determinants and/or in a sector where the genetic
      recombination between X and Y is restricted. The present evidence also supports
      our previous hypothesis that OmyP9 is organized as a tandem repeated sequence in
      the sex chromosomes of rainbow trout. We feel that the OmyP9 RsaI marker can be
      used for sex identification in crosses where it is possible to determine the
      phenotype of the parents.

PMID- 11520342
TI  - Genetic diversity of the honeybee in Africa: microsatellite and mitochondrial
      data.
AB  - A total of 738 colonies from 64 localities along the African continent have been
      analysed using the DraI RFLP of the COI-COII mitochondrial region. Mitochondrial
      DNA of African honeybees appears to be composed of three highly divergent
      lineages. The African lineage previously reported (named A) is present in almost
      all the localities except those from north-eastern Africa. In this area, two
      newly described lineages (called O and Y), putatively originating from the Near
      East, are observed in high proportion. This suggests an important differentiation
      of Ethiopian and Egyptian honeybees from those of other African areas. The A
      lineage is also present in high proportion in populations from the Iberian
      Peninsula and Sicily. Furthermore, eight populations from Morocco, Guinea, Malawi
      and South Africa have been assayed with six microsatellite loci and compared to a
      set of eight additional populations from Europe and the Middle East. The African
      populations display higher genetic variability than European populations at all
      microsatellite loci studied thus far. This suggests that African populations have
      larger effective sizes than European ones. According to their microsatellite
      allele frequencies, the eight African populations cluster together, but are
      divided in two subgroups. These are the populations from Morocco and those from
      the other African countries. The populations from southern Europe show very low
      levels of 'Africanization' at nuclear microsatellite loci. Because nuclear and
      mitochondrial DNA often display discordant patterns of differentiation in the
      honeybee, the use of both kinds of markers is preferable when assessing the
      phylogeography of Apis mellifera and to determine the taxonomic status of the
      subspecies.

PMID- 11520343
TI  - Drastic bottlenecks in the endangered crayfish species Austropotamobius pallipes
      in Spain and implications for its colonization history.
AB  - Variation in mitochondrial DNA (mtDNA) was surveyed, using restriction
      endonucleases, in the white-clawed crayfish, Austropotamobius pallipes
      lusitanicus, from 14 populations sampled in Spain. Four additional samples from
      France (1), Slovenia (1) and Italy (2) were also analysed. Among the 11
      haplotypes listed, only one was detected from the 154 animals sampled from
      Spanish populations. This haplotype was also recorded in the Fosso di Ferfereta
      population (Italy). Estimates of nucleotide sequence divergence among haplotypes
      ranged from 0.45% to 17.4%. Interpopulational genetic relationships showed that
      Spanish populations were closely related to those of Fosso di Ferfereta with a
      small genetic distance (0.0003) found between them. AMOVA revealed that most of
      the genetic variance (71.97%) was attributed to variation between European
      regions. These results are in accordance with a drastic bottleneck event during
      the history of the Spanish populations. Four suggestions, based on human
      introduction, selection and recent or ancient historical events are discussed in
      relation to the lack of genetic variation in the Spanish crayfish stock.

PMID- 11520344
TI  - Is the decline of desert bighorn sheep from infectious disease the result of low
      MHC variation?
AB  - Bighorn sheep populations have greatly declined in numbers and distribution since
      European settlement, primarily because of high susceptibility to infectious
      diseases transmitted to them from domestic livestock. It has been suggested that
      low variation at major histocompatibility complex (MHC) genes, the most important
      genetic aspect of the vertebrate immune system, may result in high susceptibility
      to infectious disease. Therefore, we examined genetic polymorphism at a MHC gene
      (Ovca-DRB) in a large sample, both numerically and geographically, of bighorn
      sheep. Strikingly, there were 21 different alleles that showed extensive
      nucleotide and amino acid sequence divergence. In other words, low MHC variation
      does not appear to be the basis of the high disease susceptibility and decline in
      bighorn sheep. On the other hand, analysis of the pattern of the MHC polymorphism
      suggested that nonsynonymous substitutions predominated, especially at amino
      acids in the antigen-binding site. The average overall heterozygosity for the 16
      amino acid positions that are part of the antigen binding site is 0.389 whereas
      that for the 67 amino acid positions not involved with antigen binding is 0.076.
      These findings imply that the diversity present in this gene is functionally
      significant and is, or has been, maintained by balancing selection. To examine
      the evolution of DRB alleles in related species, a phylogenetic analysis
      including other published ruminant (Bovidae and Cervidae) species, was carried
      out. An intermixture of sequences from bighorn sheep, domestic sheep, goats,
      cattle, bison, and musk ox was observed supporting trans-species polymorphism for
      these species. To reconcile the species and gene trees for the 104 sequences
      examined, 95 'deep coalescent' events were necessary, illustrating the importance
      of balancing selection maintaining variation over speciation events.

PMID- 11520346
TI  - Genetic analysis of sneaking and egg-thievery in a natural population of the
      three-spined stickleback (Gasterosteus aculeatus L.).
AB  - Among the fish species that show exclusive male parental care, the three-spined
      stickleback represents one of the most intensively studied species with regard to
      reproductive behaviour. In this species, the most common 'parasitic' male tactics
      in relation to male reproductive behaviour are sneaking and egg thievery, which
      are often collectively referred to as nest-raiding. However, little is known
      about the genetic consequences of sneaking and egg thievery in natural
      populations. Here we assessed the frequency of sneaking and egg-stealing in a
      natural population, male traits that are associated with the victims of sneaking,
      and the impact of sneaking and egg-stealing on the reproductive success of
      nesting males as deduced from the number of offspring in their nests. Fourteen
      nest-guarding males and a random sample of about 100 eggs/fry of each nest from a
      natural freshwater population of three-spined sticklebacks were analysed at three
      microsatellite loci. The analysis revealed a high frequency of genetically
      successful nest raiding (sneaking or egg thievery), i.e. more than half (57%) of
      the 14 nests contained offspring (1-94%) which were unrelated to the guardian
      male. Three of the 14 nests (21%) contained progeny of sneaking males and four of
      the nests (28%) contained offspring which were unrelated to the guardian male and
      which probably originated from egg-stealing events. Victims of sneaking were
      significantly smaller than other guardian males. Moreover, reproductive success
      correlated positively with male body size.

PMID- 11520345
TI  - Population genetics and dynamics of the black truffle in a man-made truffle
      field.
AB  - The colonization dynamics of the black truffle in an artificial field were
      assessed through analyses of microsatellite and RAPD markers. The truffle field
      was composed of three tree species and mycelial inoculum of three different
      origins, and was monitored for the first three years of truffle production. We
      found very low levels of genetic diversity. Isolation by distance was detected
      only at the between-tree level. This could be interpreted as local colonization
      around each tree facilitated by the presence of the tree root system. At the
      larger spatial scale of the European range, the absence of isolation by distance
      corroborates the hypothesis of an impact of glaciation on genetic variation,
      followed by rapid postglaciation demographic expansion. In addition, genetic
      variation of harvested truffles was explained by neither inoculation origin, nor
      tree species. Our study questions the real impact of man-made inoculation of tree
      root systems with fungal mycelia.

PMID- 11520347
TI  - Genetic diversity within and among Pinus pinaster populations: comparison between
      AFLP and microsatellite markers.
AB  - Twenty-three populations of Pinus pinaster (13 Aquitaine populations and 10
      Corsican populations) were analysed at three microsatellite loci and 122 AFLP
      loci. The aims of the study were: (i) to compare levels of within-population and
      among-population diversity assessed with both kinds of markers; (ii) to compare
      Aquitaine and Corsican provenances of P. pinaster; and (iii) to know if both
      markers gave the same information for conservation purposes. Classical population
      genetics statistics were estimated and the ranking of populations obtained using
      different markers and/or parameters were compared by computing Spearman's rank
      correlations. Even though microsatellites showed a higher within-population
      diversity, they showed the same level of differentiation as AFLP markers.
      Moreover, both markers also showed a higher genetic diversity in the Aquitaine
      provenance and a higher differentiation among Corsican populations. AFLPs and
      microsatellites gave different population diversity rankings. Consequently, the
      results do not support the potential population identification within each
      provenance for conservation purposes.

PMID- 11520348
TI  - Accumulation of deleterious mutations and equalization of parental contributions
      in the conservation of genetic resources.
AB  - Typical management strategies for the conservation of endangered species in
      captivity, such as equalization of family sizes, deal with the need for
      maintaining genetic variability and low levels of inbreeding, and for preventing
      the population from adapting to captivity. But they also produce a reduction in
      the intensity of natural selection, so that deleterious mutations can accumulate
      more easily in small populations. We have carried out computer simulations to
      investigate the effect of equalizing contributions on the accumulation of
      deleterious mutations. The models include effects on fecundity and viability, and
      account for different sets of mutational parameters and reproductive rates. The
      effect of relaxation of selection under captive conditions was also investigated.
      Our results suggest that equalization of family sizes does not produce a
      particularly high threat to small conserved populations, at least in the short
      term (up to about 20 generations), and the more efficient preservation of genetic
      variability seems to be a clear advantage of the procedure.

PMID- 11520349
TI  - Low neighbourhood size and high interpopulation differentiation in the endangered
      shrub Grevillea iaspicula McGill (Proteaceae).
AB  - Mating system parameters and genetic diversity were examined for five populations
      of the endangered shrub Grevillea iaspicula (Proteaceae). Controlled pollinations
      show that G. iaspicula has an effective self-incompatibility system and little
      potential for agamospermy. This is reflected in uniformly high multilocus
      outcrossing rates (tm=0.96-1.00). However, average paternal diversity within open
      pollinated sibships is low (rp=0.31-0.54), suggesting that mating within
      populations is quite restricted. Despite the small size of most populations (four
      of the five populations studied have fewer than 20 reproductive individuals) the
      species still possesses moderate to high allelic richness (A=1.6-2.5).
      Interpopulation genetic differentiation is high (D=0.04-0.32), suggesting that
      gene flow is limited, even among populations separated by only a few kilometres.

PMID- 11520350
TI  - Rickettsia associated with male-killing in a buprestid beetle.
AB  - Many populations of the buprestid leaf-mining beetle, Brachys tessellatus, from
      central South Carolina, USA, show highly skewed sex ratios, ranging from 1.3 to
      6.0 females per male. We have identified a Rickettsia bacterium that is
      associated with sex ratio distortion (SRD) and selective killing of male embryos
      in B. tessellatus. Molecular assays of infection by this bacterium are highly
      associated with SRD within families, and treatment with an antibiotic
      (tetracycline) increases the number of male eggs that hatch and develop. The 16S
      rDNA sequence indicates that this is a novel Rickettsia, most closely related to
      Rickettsia bellii (a tick-associated bacterium) and a pea-aphid Rickettsia. It is
      also related to a Rickettsial bacterium that causes male-killing in an unrelated
      ladybird beetle species. Low levels of parthenogenesis are also observed in this
      system (about 10% of females) and may be the result of selection due to male
      rarity, or a direct result of infection by the Rickettsia.

PMID- 11520351
TI  - Variability levels, population size and structure of American and European
      Drosophila montana populations.
AB  - The level and patterns of nucleotide diversity have been characterized for two X
      linked loci, fused (fu; a region of 2362 bp) and suppressor of sable (su(s); a
      region of 413 bp), in one European and one American D. montana population.
      Sequence variation at these loci shows that the two populations are divergent,
      although they may not be completely isolated. Data on the level of silent site
      variability at su(s) (1.1% and 0.5% for the European and American populations,
      respectively) suggest that the effective population sizes of the two populations
      may be similar. At the fused locus, one European sequence was highly divergent
      and may have resulted from gene conversion, and was excluded from the analysis.
      With this sequence removed, the level of silent site variability was
      significantly lower in the European population (0.28%) than in the American
      population (2.3%), which suggests a selective sweep at or near fu in the former
      population.

PMID- 11520352
TI  - Purification, characterization and gene expression of a glycine and proline-rich
      antibacterial protein family from larvae of a beetle, Allomyrina dichotoma.
AB  - Two structurally related antibacterial proteins were isolated from larvae of a
      beetle, Allomyrina dichotoma, immunized with Escherichia coli. The two proteins
      were designated A. dichotoma (A. d.) coleoptericin A and B. The mature portion of
      A. d. coleoptericins deduced from nucleotide sequences of the cDNAs consists of
      seventy-two amino acids without cysteine residues and is rich in glycine (11.1%)
      and proline (11.1%). Comparison of the amino acid sequences of the A. d.
      coleoptericins revealed that these antibacterial proteins have 94%, 75%, 50% and
      43% similarity to rhinocerosin, holotricin 2, coleoptericin and acaloleptin A1.
      Recombinant A. d. coleoptericin A and B showed strong antibacterial activity
      against Staphylococcus aureus, methicillin resistant S. aureus (MRSA) and
      Bacillus subtilis. Recombinant A. d. coleoptericin A and B were shown to not form
      pores through bacterial membranes of E. coli, but to hamper cell division.
      Results of Northern blotting showed that A. d. coleoptericin genes are inducible
      by bacteria and are expressed strongly in the fat bodies and haemocytes, and
      weakly in the Malpighian tubules. Analysis of the evolutionary relationship of
      amino acid sequences among A. d. coleoptericins and other antibacterial proteins
      suggests that A. d. coleoptericins, rhinocerosin and holotricin 2 are closely
      related and form a gene family.

PMID- 11520353
TI  - Molecular phylogeny of Diabrotica beetles (Coleoptera: Chrysomelidae) inferred
      from analysis of combined mitochondrial and nuclear DNA sequences.
AB  - The phylogenetic relationships of thirteen Diabrotica (representing virgifera and
      fucata species groups) and two outgroup Acalymma beetle species (Coleoptera:
      Chrysomelidae) were inferred from the phylogenetic analysis of a combined data
      set of 1323 bp of mitochondrial DNA (mtDNA) cytochrome oxidase subunit 1 (COI)
      and the entire second internal transcribed spacer region (ITS-2) of nuclear
      ribosomal DNA of 362 characters. Species investigated were D. adelpha, D.
      balteata, D. barberi, D. cristata, D. lemniscata, D. longicornis, D. porracea, D.
      speciosa, D. undecimpunctata howardi, D. u. undecimpunctata, D. virgifera
      virgifera, D. v. zeae, D. viridula, and outgroup A. blandulum and A. vittatum.
      Maximum parsimony (MP), minimum evolution (ME), and maximum likelihood (ML)
      analyses of combined COI and ITS-2 sequences clearly place species into their
      traditional morphological species groups with MP and ME analyses resulting in
      identical topologies. Results generally confer with a prior work based on
      allozyme data, but within the virgifera species group, D. barberi and D.
      longicornis strongly resolve as sister taxa as well as monophyletic with the
      neotropical species, D. viridula, D. cristata and D. lemniscata also resolve as
      sister taxa. Both relationships are not in congruence with the prior allozyme
      based hypothesis. Within the fucata species group, D. speciosa and D. balteata
      resolve as sister taxa. Results also strongly supported the D. virgifera and D.
      undecimpunctata subspecies complexes. Our proposed phylogeny provides some
      insight into current hypotheses regarding distribution status and evolution of
      various life history traits for Diabrotica.

PMID- 11520354
TI  - Effect of prophenoloxidase expression knockout on the melanization of
      microfilariae in the mosquito Armigeres subalbatus.
AB  - Melanization is an effective defence reaction used by mosquito hosts to kill
      malarial and filarial worm parasites. Although phenoloxidase (PO) has long been
      considered to be the key enzyme in the biosynthesis of melanotic material in
      insects, there is no direct evidence verifying its role in parasite melanization.
      To elucidate the role of PO in the melanization of microfilariae (mf) by
      mosquitoes, a double subgenomic Sindbis (dsSIN) recombinant virus was used to
      transduce Armigeres subalbatus mosquitoes with a 600 base antisense RNA targeted
      to the highly conserved copper-binding region of an Ar. subalbatus PO gene.
      Compared with controls, haemolymph PO activity in mosquitoes transduced with
      antisense RNA was significantly reduced. When these mosquitoes were challenged
      with Dirofilaria immitis mf, the melanization of mf was almost completely
      inhibited. These data verify that PO is an essential component of the biochemical
      pathway required for the melanization of parasites, and that the dsSIN expression
      system represents a useful tool in the functional analysis of endogenous gene
      expression in mosquitoes.

PMID- 11520356
TI  - Characterization of muscle actin genes in Drosophila virilis reveals significant
      molecular complexity in skeletal muscle types.
AB  - Actin is a ubiquitous and highly conserved eukaryotic protein required for cell
      motility and locomotion. In this manuscript, we characterize the four muscle
      actin genes of the insect Drosophila virilis and demonstrate strong similarities
      between the D. virilis genes and their homologues in Drosophila melanogaster;
      intron locations are conserved, and there are few amino acid differences between
      homologues. We also found strong conservation in temporal expression patterns of
      the muscle actin genes--the homologues of the D. melanogaster genes Act57B and
      Act87E are expressed throughout the life cycle, whereas the other two D. virilis
      genes, homologous to Act79B and Act88F are specific to pupal and adult stages. In
      situ hybridization revealed that each D. virilis gene is expressed in a unique
      pattern in the muscles of the thorax and abdomen. These muscle-specific patterns
      of actin isoforms suggest a greater physiological diversity for the adult muscles
      of insects than has been appreciated to date from their categorization into
      fibrillar, tubular (non-fibrillar) and supercontractile muscle types.

PMID- 11520357
TI  - Corazonin gene expression in the waxmoth Galleria mellonella.
AB  - We cloned and sequenced a full length cDNA coding for [Arg7]-corazonin in the
      greater wax moth Galleria mellonella. The deduced corazonin preprohormone
      consists of a nineteen amino acid signal peptide, the actual eleven amino acid
      corazonin sequence, followed by a Gly serving for amidation, a Lys-Arg processing
      site and an eighty amino acid corazonin precursor-related peptide. The data
      confirm the phylogenetic conservation of the actual corazonin sequence. The
      signal peptide and the precursor-related peptide exhibit a similar spacing of a
      few amino acids as detected in the corazonin preprohormone of Drosophila
      melanogaster. Northern blots and in situ hybridization experiments revealed that
      the G. mellonella corazonin gene is tissue-specifically expressed in four pairs
      of lateral neurosecretory cells in the brains of penultimate and last instar
      larvae, as well as of pupae and adults. No corazonin mRNA was detected in other
      cells of the nervous system, fat body, gut, and several other organs.

PMID- 11520355
TI  - Identification and characterization of a homologue of the pro-inflammatory
      cytokine Macrophage Migration Inhibitory Factor in the tick, Amblyomma
      americanum.
AB  - Studying tick feeding and digestion, we discovered in a cDNA library from
      partially fed Amblyomma americanum ticks the first known arthropod homologue of a
      human cytokine, the pro-inflammatory Macrophage Migration Inhibitory Factor
      (MIF). The tick origin of the MIF cDNA clone was confirmed by sequencing a
      genomic fragment that contained the full-length tick MIF gene with two introns.
      Antiserum to a tick MIF-specific peptide as well as antiserum to complete tick
      MIF revealed the expression of tick MIF in the salivary gland and midgut tissues
      of A. americanum ticks. In an in vitro functional assay, recombinant tick MIF
      inhibited the migration of human macrophages to the same extent that recombinant
      human MIF did.

PMID- 11520358
TI  - Effects of malaria infection on vitellogenesis in Anopheles gambiae during two
      gonotrophic cycles.
AB  - We report changes in the abundance of vitellogenin (Vg) mRNA, and concentration
      of haemolymph Vg and ovarian vitellin (Vn) in Anopheles gambiae following
      infection with Plasmodium yoelii nigeriensis. A parasite-induced reduction in Vg
      mRNA abundance was first detected 24 h after feeding on an infective blood meal,
      when ookinetes were invading the midgut. During a second gonotrophic cycle post
      infection, developing oocysts reduced Vg mRNA abundance by up to 33% and the
      effect was detected from 2 h post blood meal. Concentrations of Vg were initially
      reduced by infection during the second cycle, as predicted from Vg mRNA
      measurements. However, after 24 h, excess Vg had accumulated in the haemolymph.
      This accumulation may be due to impaired uptake, since ovarian vitellin
      accumulation was significantly decreased by infection during both gonotrophic
      cycles.

PMID- 11520360
TI  - The genome of the Queensland fruit fly Bactrocera tryoni contains multiple
      representatives of the mariner family of transposable elements.
AB  - Representatives of five distinct types of transposable elements of the mariner
      family were detected in the genomes of the Queensland fruit fly Bactrocera tryoni
      and its sibling species Bactrocera neohumeralis by phylogenetic analysis of
      transposase gene fragments. Three mariner types were also found in an additional
      tephritid, Bactrocera jarvisi. Using genomic library screening and inverse PCR,
      full-length elements representing the mellifera subfamily (B. tryoni.mar1) and
      the irritans subfamily (B. tryoni.mar2) were isolated from the B. tryoni genome.
      Nucleotide consensus sequences for each type were derived from multiple defective
      copies. Predicted transposase sequences share approximately 23% amino acid
      identity. B. tryoni.mar1 elements have an estimated copy number of about 900 in
      the B. tryoni genome, whereas B. tryoni.mar2 element types appear to be present
      in low copy number.

PMID- 11520359
TI  - Cloning and expression analysis of a 5HT7-like serotonin receptor cDNA from
      mosquito Aedes aegypti female excretory and respiratory systems.
AB  - In the mosquito Aedes aegypti, 5-HT changes the endogenous rhythm of contractions
      in the female hindgut and increases fluid secretion in the larval Malpighian
      tubule. The role of 5-HT as a diuretic hormone in adults has been questioned. We
      cloned a cDNA encoding a serotonin receptor from a female A. aegypti Malpighian
      tubule library that is similar to the 5-HT7 receptor from Drosophila
      melanogaster. The transcript was localized in the tracheolar cells associated
      with the female Malpighian tubules but no signal was detectable in the tubule
      epithelium. Immunohistochemistry with specific antibodies confirmed the receptor
      expression in tracheolar cells and hindgut, and western blots of these tissues
      showed the expected 50 kDa band. The results suggest a role for serotonin in
      respiration and that this receptor may coordinate the tubule-hindgut response to
      serotonin during diuresis.

PMID- 11520362
TI  - Surgical management of stage I and II vulvar cancer: the role of the sentinel
      node biopsy. Review of literature.
AB  - Recognition of the psychosexual consequences of radical vulvectomy and better
      understanding of the lymphatic drainage and histopathologic features of vulvar
      cancer have led to a more conservative surgical approach, especially in patients
      with early-stage disease. Every patient with early vulvar cancer should be
      managed individually and the risk of conservative therapy balanced against the
      dangers and advantages of more radical therapy. The results of the sentinel node
      (SN) procedure in early cancer of the vulva are encouraging, and it might be
      possible in the near future to avoid the morbidity of inguino-femoral
      lymphadenectomy. This article reviews surgical management of early vulvar cancer
      and the place of SN biopsy.

PMID- 11520363
TI  - A comparison of MRI and PET scanning in surgically staged loco-regionally
      advanced cervical cancer: potential impact on treatment.
AB  - The aim of this study was to assess whether positron emission tomography (PET) or
      magnetic resonance imaging (MRI) could obviate the need for surgical staging in
      patients with locally advanced cervical carcinoma being planned for radiotherapy
      (RT). Imaging findings were compared to surgical staging in 27 patients including
      three with recent resection of the primary tumor. Both PET and MRI visualized all
      24 residual cervical tumors. Primary tumor volume, as measured by MRI scan,
      ranged from 1.25 cc to 140 cc. In 24 patients evaluable for pelvic nodal status,
      PET had sensitivity, specificity, and positive and negative predictive values of
      83%, 92%, 91% and 85%, respectively, with 88% accuracy. MRI detected only six in
      12 (50%) patients with confirmed pelvic nodal disease, all of which were also
      seen by CT and PET, with an overall accuracy of 75%. PET detected only four in
      seven (57%) cases with confirmed para-aortic (PA) involvement. All histologically
      confirmed sites not visualized on PET were <1 cm. Without surgical staging, six
      in 10 (60%) patients with histologically proven pelvic nodal disease would not
      have received pelvic boost if guided by MRI alone, compared to two in 10 (20%)
      patients guided by PET alone or in combination with MRI. All four patients with
      positive PA on PET were confirmed on histology or clinical follow-up, including
      one case that proved to be a false negative one on surgery. However, in three
      cases, PET would have yielded an inadequate radiation volume. In conclusion, the
      positive predictive value of PET in the pelvis and para-aortic region appears
      sufficient to obviate lymph nodal sampling, but sampling is still required to
      exclude small-volume disease cranial to sites of abnormality on PET. MRI has
      insufficient accuracy for nodal staging to impact management.

PMID- 11520361
TI  - Genetic differentiation of Glossina morsitans centralis populations.
AB  - Variation at mitochondrial and microsatellite loci was used to study the breeding
      and dispersal structure of Glossina morsitans centralis, in six natural
      populations from Botswana, the Caprivi Strip (Namibia), Zambia, and in a
      laboratory culture derived from Singida, Tanzania. Only seven mitochondrial
      haplotypes were found. Mean diversity averaged over the six natural populations
      was 0.216 +/- 0.085. The fixation index FST = 0.866 indicated a high degree of
      genetic differentiation among populations. Fifty-three alleles were detected
      among six microsatellite loci and six natural populations. Mean microsatellite
      diversity was 0.702 +/- 0.091. Depending on the estimating model used, fixation
      indices varied from 0.15 to 0.225 confirming that G. m. centralis populations are
      strongly subdivided. For all FST estimates, positive correlations were detected
      between pair-wise genetic distance measures and geographical distances. The
      difference in fixation indices estimated from mitochondrial or nuclear loci was
      explained by the greater sensitivity of mitochondrial genomes to genetic drift.
      Population differentiation can be explained by genetic drift and the subsequent
      recovery of extant populations from small, discontinuous populations. These data
      confirm genetically the collapse and retreat of G. m. centralis populations
      caused by the rinderpest epizootic of the late 19th and early 20th centuries.

PMID- 11520364
TI  - Subsequent endometrial carcinoma with adjuvant tamoxifen treatment in Japanese
      breast cancer patients.
AB  - This study aimed to detail the clinicopathologic features of endometrial
      carcinomas that developed in Japanese patients receiving adjuvant tamoxifen
      treatment for breast cancer patients. Ten endometrial carcinomas in tamoxifen
      treated breast cancer patients were collected from two medical centers. The
      endometrial carcinomas included two stage Ia, four stage Ib, two stage Ic and two
      stage IIIc. Three tumors were Grade 1, six were Grade 2, and one was Grade 3. The
      tumor was limited to the endometrium in two cases. Myometrial invasion was
      limited to the inner half of the myometrium in five cases and involved the outer
      half in three. A mild degree of lymphovascular space invasion was identified in
      five cases. Deep cervical invasion was recognized in one case. The cell types
      comprised nine endometrioid adenocarcinomas and one serous carcinoma. Five of
      eight postmenopausal endometrial carcinomas were associated with polypoid
      endometrial lesions composed of cystically dilated atrophic and proliferative
      glands widely separated by fibrotic stroma. Two patients with retroperitoneal
      lymph node metastases died of endometrial cancer. One patient developed a
      contralateral breast cancer during tamoxifen treatment. No patient died of breast
      cancer. We did not demonstrate a higher frequency of either high-grade tumors or
      unfavorable histologic subtypes in tamoxifen-treated Japanese breast cancer
      patients.

PMID- 11520365
TI  - The clinical relevance of serum CYFRA 21-1 assay in patients with ovarian cancer.
AB  - CYFRA 21-1 assay, which detects serum fragments of cytokeratin 19, has been
      widely assessed as a serum marker of several malignancies. Preoperative serum
      CYFRA 21-1 levels were retrospectively measured in 60 patients with ovarian
      cancer and in 59 control patients with benign ovarian disease. CYFRA 21-1 levels
      were also serially measured in 90 serum samples drawn from patients with advanced
      (FIGO stage III-IV) ovarian cancer followed after surgery and chemotherapy.
      Preoperative serum CYFRA 21-1 levels were higher in patients with ovarian cancer
      compared with controls (median, range = 2.6, 0.1-51.4 ng/ml versus 0.4, 0.0-3.6
      ng/ml, P < 0.0001), and among the former, antigen values were higher in the 39
      patients with advanced-stage than in the 21 patients with early (FIGO stage I-II)
      disease (P < 0.0001). In advanced ovarian cancer patients, the 25%, 50%, and 75%
      quantiles of preoperative CYFRA 21-1 levels were 1.9, 4.8 and 14.4 ng/ml,
      respectively. Preoperative CYFRA 21-1 levels were lower in the 11 patients who
      achieved a pathologic complete response at second-look compared with those who
      had clinically or surgically detectable persistent disease after first-line
      chemotherapy (median, range 1.9, 0.6-9.2 ng/ml versus 10.2, 0.1-51.4 ng/ml, P =
      0.007). The pathologic complete response rate was significantly greater in
      patients with low preoperative CYFRA 21-1 levels compared with those with
      elevated CYFRA 21-1 levels at any cut-off limit for the antigen (1.9, 4.8 and
      14.4 ng/ml). However, Cox regression analysis failed to detect a significant
      association between preoperative CYFRA 21-1 assay and survival. As for the follow
      up of advanced ovarian cancer patients, CYFRA 21-1 levels were higher in the 42
      samples drawn from patients with clinically detectable disease compared with the
      48 specimens collected from patients with no clinical evidence of disease
      (median, range = 1.15, 0.3-40.7 ng/ml versus 0.4, 0.1-9.1 ng/ml, P < 0.0001). In
      conclusion, preoperative serum CYFRA 21-1 assay appears to be predictive of
      response to chemotherapy, but not prognostic of survival, for patients with
      advanced ovarian cancer. Moreover, the serial measurement of CYFRA 21-1 levels
      might have a potential clinical relevance for the assessment of disease status in
      patients followed after surgery and chemotherapy.

PMID- 11520366
TI  - Uterine serous papillary carcinoma: histopathologic changes within the female
      genital tract.
AB  - The histopathologic features of 25 patients with uterine serous papillary
      carcinoma (USPC) were presented, with particular emphasis on the changes seen in
      the remaining mullerian epithelium. The mean age at presentation was 68.9 years;
      52% of patients were stage III at the time of presentation and 40% died of their
      disease within 24 months of diagnosis. Histologic assessment revealed: 1) pure
      serous carcinoma in 56% of patients and mixed differentiation of serous and
      endometrioid in the remainder; 2) malignant epithelium reminiscent of that of
      USPC and akin to carcinoma in situ, frequently seen in the remaining endometrium,
      cervix, and, less commonly, the fallopian tube; 3) residual endometrium that,
      when identified (11/25 cases), was atrophic in all cases; 4) various types of
      cervical involvement in 17 cases (68%); 5) tumor within the fallopian tube in
      three cases (12%); and 6) carcinoma with in situ-like features in five cases
      (20%). In conclusion, it appears that USPC is frequently associated with
      malignant epithelial changes (as with carcinoma in situ) in the remaining
      mullerian epithelium. This finding suggests either a field change or, more
      likely, a transepithelial tumor spread. The latter theory is preferable, because
      this type of spread is frequently seen on serosal surfaces in cases of serous
      ovarian carcinoma. Uterine serous papillary carcinoma is, therefore, biologically
      more akin to its ovarian counterpart.

PMID- 11520367
TI  - Peritoneal tuberculosis with pelvic abdominal mass, ascites and elevated CA 125
      mimicking advanced ovarian carcinoma: a series of 10 cases.
AB  - Ten patients with peritoneal tuberculosis who were operated on for suspected
      advanced ovarian cancer during a 5-year period were analyzed. These 10 cases
      constituted 1.4% of the 728 new gynecologic cancer cases diagnosed and treated at
      our department during the same time period. Data were obtained from patients'
      files and pathology reports. The mean age of cases was 40.6 +/- 6.1 (median 37;
      range 18-72). Ascites was present together with ill-defined nodularities or
      thickening in the Douglas pouch and/or in the adnexal areas on pelvic examination
      in all patients but three, who presented with well-demarcated adnexal masses of
      about 5 cm in diameter. All patients had elevated serum CA 125 levels with a
      median of 331 U/ml, (40-560 U/ml). Ultrasound and abdominopelvic CT examinations
      revealed omental and mesenteric thickening in addition to ascites in all
      patients, cystic ovarian masses or ovarian enlargement in five, and peritoneal
      implants in two. Abdominal paracentesis performed in the six cases in whom the
      findings were felt to be most inconclusive for the diagnosis of ovarian cancer
      revealed clear exudative fluid with benign cells. Mycobacteria could not be
      demonstrated on direct preparations. Tuberculosis was diagnosed at laparotomy in
      all. Patients received antituberculous therapy and serum CA 125 levels returned
      to normal within 2 months after the beginning of treatment. This case series
      demonstrates a high rate of misdiagnosis between advanced ovarian cancer and
      peritoneal tuberculosis. Whereas abdominal paracentesis is useless in ruling out
      peritoneal tuberculosis, and serum CA 125 levels are not helpful in the
      differential diagnosis, the latter marker may be useful in the follow-up of
      patients.

PMID- 11520368
TI  - Weekly and monthly regimens of paclitaxel and carboplatin in the management of
      advanced ovarian cancer. A preliminary report on side effects.
AB  - This preliminary study was carried out over 18 months to evaluate whether the
      side effects in patients with advanced ovarian cancer receiving chemotherapy
      using paclitaxel-carboplatin differed between weekly (98 cycles in 14 patients)
      and monthly (102 cycles in 15 patients) administrations. We used paclitaxel (60
      mg/m2) and carboplatin (AUC of 2) in the weekly regimen and 175 mg/m2 of
      paclitaxel and carboplatin (AUC of 6) in the monthly regimen. All eligible
      patients received at least four cycles of treatment in both regimens. The results
      revealed significantly decreased hematological toxicity in weekly regimens
      relative to monthly ones, ie, 7.1% vs. 18.6% of anemia (> or = grade 2), 7.1% vs.
      32.3% of grade 3/4 granulocytopenia, and 0% vs. 15.7% of >grade 2
      thrombocytopenia. There was no significant difference in nonhematological
      toxicities between the two regimens. The incidence of unscheduled events was much
      less in the weekly regimen than in the monthly one; ie, delayed treatment (3 vs.
      18 events), unanticipated hospitalizations (3 vs. 15 times), and supplemental
      support with G-CSF (7 vs. 33 times). Complete responses were observed in 6 of 14
      patients in the weekly regimen and in five of 15 patients in the monthly regimen,
      while partial responses were seen in four and five patients in the weekly and
      monthly regimens, respectively. The present results demonstrate that the weekly
      regimen can achieve the benefits of tolerable toxicity with significantly reduced
      myelosuppression and improved cost-effectiveness in terms of unscheduled events.

PMID- 11520369
TI  - Germ cell tumors of the ovary: is there a role for aggressive cytoreductive
      surgery for nondysgerminomatous tumors?
AB  - Thirty-three patients with germ cell tumor of the ovary were seen at Kidwai
      Memorial Institute of Oncology (KMIO), Bangalore, between 1996 and 1999. Twelve
      patients had endodermal sinus tumor (EST), 11 dysgerminoma, seven mixed germ cell
      tumor, and three immature teratoma. Thirteen patients had bulky residual disease
      of >10 cm after the primary surgery. All but one patient received a combination
      of bleomycin, etoposide, and cisplatin (BEP) either as neoadjuvant (NACT, 3
      cases) or as adjuvant therapy (28 cases). In the present study, all 11 patients
      with dysgerminoma achieved sustained complete remission (CR), irrespective of the
      size of residual disease at the time of chemotherapy. Four out of six cases
      (66.6%) with bulky nondysgerminomatous tumor achieved CR, which was sustained in
      three cases and one recurred. Fifteen of the remaining 16 (93.7%) nonbulky,
      nondysgerminomatous tumors achieved CR, which was sustained in 14 cases and
      recurred in one. This study indicates that there may be a role for aggressive
      cytoreductive surgery, either primary/interval or at the time of second-look
      laparotomy, in selected patients with nondysgerminomatous germ cell tumor of the
      ovary.

PMID- 11520370
TI  - Prognosis for papillary serous carcinoma of the endometrium after surgical
      staging.
AB  - BACKGROUND: To investigate the pattern of failure and the prognosis following
      pathological staging for uterine papillary serous carcinoma (UPSC). PATIENTS AND
      METHODS: A retrospective review was conducted of 22 patients with UPSC, treated
      between 1989 and 1998 at a single institution. All patients were surgically
      staged. Two patients with advanced disease received chemotherapy only. Two
      patients with early-stage disease were followed without further treatment.
      Eighteen patients received postoperative irradiation; eight patients received
      whole abdominal irradiation (WART), and the remaining 10 patients, pelvic
      irradiation (PRT). In addition, seven of these patients received vaginal cuff
      irradiation with low-dose-rate or high-dose-rate brachytherapy. Toxicity, pattern
      of failure, and survival were evaluated and compared to the literature. RESULTS:
      Seven patients (32%) developed distant metastases, three out of seven (42%) after
      WART. Four out of seven patients who had distant metastases died from disease
      progression during subsequent chemotherapy. All patients with distant metastases
      had locally advanced-stage disease at presentation (six stage III, one stage IV).
      Four patients with pelvic recurrences developed concurrent (2) and subsequent (2)
      distant metastases. Three patients had isolated distant metastases. No patient
      with early stage-disease (stage I and II) died from disease progression.
      CONCLUSION: Pathological staging should be performed for all patients with UPSC
      to determine the prognosis as well as to tailor the treatment. The role of
      abdominal irradiation in the treatment of UPSC is yet to be determined; however,
      such an approach may not be necessary for the control of disease for patients
      with early-stage (I and II) disease. Patients with locally advanced-stage (stage
      III) disease are at risk of local regional failures and distant metastases
      despite WART. Therefore, the benefit of WART for advanced-stage disease is also
      questionable. Paclitaxel-based chemotherapy is currently being investigated in
      this setting.

PMID- 11520371
TI  - Leiomyomatosis peritonealis disseminata and ovarian Brenner tumor associated with
      tamoxifen use.
AB  - Tamoxifen is frequently administered as adjuvant therapy for breast carcinoma and
      produces weak estrogen agonist effects in estrogen sensitive tissues. In addition
      to producing a measurable increase in the risk of endometrial carcinoma,
      tamoxifen has also been associated with increasing size of uterine leiomyomata as
      well as the development of new leiomyomata. As the indications for tamoxifen
      therapy expand, surveillance for additional potential associated adverse outcomes
      is warranted. A 44-year-old woman with a history of bilateral breast carcinoma
      presented with leiomyomatosis peritonealis disseminata and a right ovarian
      Brenner tumor 18 months after beginning adjuvant tamoxifen therapy. Although a
      causal link cannot be proven, this case is the second reported association
      between leiomyomatosis peritonealis disseminata, an ovarian Brenner tumor, and
      tamoxifen use for the treatment of breast carcinoma. Given the hormonal
      sensitivity of leiomyomatosis peritonealis disseminata, both mutagenic and
      mitogenic effects of tamoxifen on this rare entity must be considered. In the
      setting of continued hormonal treatment for breast carcinoma, the management of
      leiomyomatosis peritonealis disseminata presents unique clinical challenges.

PMID- 11520372
TI  - Primary epithelioid sarcoma of the vulva.
AB  - A case of a 31-year-old woman with epithelioid sarcoma of the vulva which
      metastasized to the regional lymph node 8 years after onset of the disease is
      reported here. The patient first noticed a painless subcutaneous mass of 5 mm in
      diameter in the right labium majus at age of 21. This was excised locally at age
      23, but recurred 17 months later. Although local excision was again performed,
      the tumor recurred and continued to enlarge very slowly. At this stage, based on
      the pathology of both the initial and second tumors, the diagnosis was of a
      benign inflammatory process. However, local recurrence and inguinal lymph node
      swelling occurred at age 29, and biopsy was taken. The pathology report indicated
      benign granulomatous changes. The slides were reconsidered and re-interpreted as
      epithelioid sarcoma, whereupon radical vulvectomy was performed at age 31. Vulvar
      epithelioid sarcoma with inguinal lymph node metastasis was first diagnosed at
      that time. Epithelioid sarcoma of the vulva is an exceedingly rare tumor, and
      only 15 cases have been reported thus far in the literature. Early diagnosis and
      curative treatment of this tumor may be problematic for gynecologists because of
      its rarity and therefore little-known characteristic clinical behavior and
      histology. Radical vulvectomy or extensive local excision with inguinal
      lymphadenectomy at the time of diagnosis is recommended as the treatment of
      choice.

PMID- 11520373
TI  - Vulval myxoid liposarcoma.
AB  - A 26 year old woman presented with a 4-year history of a gradually enlarging
      fluctuant mass on the left labium majus. Histologic examination following
      excision revealed myxoid liposarcoma. Following the diagnosis, further surgery
      was performed to ensure complete resection. Routine excision of draining lymph
      nodes is not advocated. Although rare, myxoid liposarcoma should be considered in
      the differential diagnosis of a vulval soft tissue mass.

PMID- 11520374
TI  - Multisystem sarcoidosis and carcinoma of the uterine cervix: an unusual
      association.
AB  - Sarcoidosis malignancy syndrome is a rare phenomenon which remains controversial.
      We report here the case of a 46-year-old woman presenting with multisystem
      sarcoidosis 12 months after the completion of combined treatment for stage III
      squamous cell carcinoma of the uterine cervix; at the time she was still in
      complete remission of the tumor. The outcome was rapidly favorable under oral
      corticosteroid therapy. The time interval between the two illnesses as well as
      patient's age strongly suggest a relationship. Possible pathophysiologic
      mechanisms and the literature regarding uterine tumors are briefly reviewed.

PMID- 11520375
TI  - Atypical polypoid adenomyoma in a patient with hyperprolactinemia.
AB  - We report a case of an atypical polypoid adenomyoma in a patient with
      hyperprolactinemia. A 23-year-old Japanese woman was admitted complaining of
      atypical genital bleeding. Specula examination revealed a walnut-size polypoid
      mass extruding from the cervix. The patient was oligomenorrheac, and endocrine
      analysis showed hyperprolactinemia. Transvaginal ultrasonography and magnetic
      resonance imaging revealed an endometrial polypoid mass (4 x 3 x 3 cm) arising
      from the lower segment of the uterine corpus. The pathologic diagnosis of the
      tumor after polypectomy was atypical polypoid adenomyoma. It is suggested that
      ovarian dysfunction caused by hyperprolactinemia may be involved in the
      pathogenesis of atypical polypoid adenomyoma in the present case.

PMID- 11520376
TI  - Choriocarcinoma and human immunodeficiency virus (HIV) infection: a case report.
AB  - The appropriate management of gynecological malignancies in human
      immunodeficiency virus (HIV)-infected patients is uncertain. Gestational
      trophoblastic disease is highly curable and occurs predominantly among young
      females. However, such patients are often immunocompromised and cytotoxic agents
      may further compromise immunity. This case report demonstrates the successful
      management of choriocarcinoma in a HIV-infected patient.

PMID- 11520377
TI  - Ovarian fibrosarcoma with long-term survival: a case report.
AB  - Primary ovarian fibrosarcoma is an exceedingly rare malignant ovarian stromal
      tumor which has a poor prognosis. We report here a 46-year-old woman who suffered
      from irregular vaginal bleeding for 2 months. She received hysterectomy and
      salpingo-oophorectomy due to a provisional diagnosis of uterine and ovarian
      tumors. At surgery, an 8-cm ovarian solid multilobular tumor was found. Frozen
      section examination revealed an ovarian fibrosarcoma. She then underwent staging
      procedures including intraperitoneal washing, cytology, and pelvic and para
      aortic lymph node sampling. Final pathologic examination revealed that the tumor
      exhibited densely packed spindle cells in storiform configuration with obvious
      increased mitotic activity. In addition, the flow cytometric study showed marked
      elevated percentage of tumor cells in the S phase (13.1%). After surgery, the
      patient received six courses of combination chemotherapy with epirubicin,
      ifosfamide, and dacarbazine (DTIC). The patient stood the treatment well and is
      free from disease 6 years later.

PMID- 11520378
TI  - Coexistence of metastatic neuroendocrine carcinoma of the uterine cervix with
      human immunodeficiency virus infection.
AB  - Women now constitute 28% of new cases of human immunodeficiency virus (HIV)
      infection. Cervical cancer in HIV-infected women has a high recurrence and death
      rate, as well as decreased intervals to recurrence and death. Neuroendocrine
      carcinomas of the cervix are characterized by a high frequency of early nodal and
      distant metastases. We present the first report of a neuroendocrine carcinoma of
      the cervix in an HIV-positive patient. A 28 year old with a 9-year history of HIV
      succumbed to metastatic neuroendocrine carcinoma of the cervix 5 months after
      diagnosis. Given the aggressive nature of the cell type, an extended metastatic
      workup should be considered prior to surgery. The immune suppression present in
      HIV-positive patients with neuroendocrine cervical carcinoma may make such a
      workup particularly crucial, such that surgery is offered only to those who can
      be expected to benefit.

PMID- 11520379
TI  - Effectiveness of a focused educational intervention on resident evaluations from
      faculty a randomized controlled trial.
AB  - OBJECTIVE: To improve the quality and specificity of written evaluations by
      faculty attendings of internal medicine residents during inpatient rotations.
      DESIGN: Prospective randomized controlled trial. SETTING: Four hospitals:
      tertiary care university hospital, Veterans' Administration hospital, and two
      community hospitals. PARTICIPANTS: Eighty-eight faculty and 157 residents from
      categorical and primary-care internal medicine residency training programs
      rotating on inpatient general medicine teams. INTERVENTION: Focused 20-minute
      educational session on evaluation and feedback, accompanied by 3 by 5 reminder
      card and diary, given to faculty at the start of their attending month.
      MEASUREMENTS AND MAIN RESULTS:  PRIMARY OUTCOMES: 1) number of written comments
      from faculty specific to unique, preselected dimensions of competence; 2) number
      of written comments from faculty describing a specific resident behavior or
      providing a recommendation; and 3) resident Likert-scale ratings of the quantity
      and effect of feedback received from faculty. Faculty in the intervention group
      provided more written comments specific to defined dimensions of competence, a
      median of three comments per evaluation form versus two in the control group, but
      when adjusted for clustering by faculty, the difference was not statistically
      significant (P =.09). Regarding feedback, residents in the intervention group
      rated the quantity significantly higher (P =.04) and were significantly more
      likely to make changes in clinical management of patients than residents in the
      control group (P =.04). CONCLUSIONS: A brief, focused educational intervention
      delivered to faculty prior to the start of a ward rotation appears to have a
      modest effect on faculty behavior for written evaluations and promoted higher
      quality feedback given to house staff.

PMID- 11520380
TI  - Effect of computer support on younger women with breast cancer.
AB  - OBJECTIVE: Assess impact of a computer-based patient support system on quality of
      life in younger women with breast cancer, with particular emphasis on assisting
      the underserved. DESIGN: Randomized controlled trial conducted between 1995 and
      1998. SETTING: Five sites: two teaching hospitals (Madison, Wis, and Chicago,
      Ill), two nonteaching hospitals (Chicago), and a cancer resource center
      (Indianapolis, Ill). The latter three sites treat many underserved patients.
      PARTICIPANTS: Newly diagnosed breast cancer patients (N = 246) under age 60.
      INTERVENTIONS: Experimental group received Comprehensive Health Enhancement
      Support System (CHESS), a home-based computer system providing information,
      decision-making, and emotional support. MEASUREMENTS AND MAIN RESULTS: Pretest
      and two post-test surveys (at two- and five-month follow-up) measured aspects of
      participation in care, social/information support, and quality of life. At two
      month follow-up, the CHESS group was significantly more competent at seeking
      information, more comfortable participating in care, and had greater confidence
      in doctor(s). At five-month follow-up, the CHESS group had significantly better
      social support and also greater information competence. In addition, experimental
      assignment interacted with several indicators of medical underservice (race,
      education, and lack of insurance), such that CHESS benefits were greater for the
      disadvantaged than the advantaged group. CONCLUSIONS: Computer-based patient
      support systems such as CHESS may benefit patients by providing information and
      social support, and increasing their participation in health care. These benefits
      may be largest for currently underserved populations.

PMID- 11520381
TI  - Validation of a telephone-administered geriatric depression scale in a hispanic
      elderly population.
AB  - OBJECTIVE: To develop and validate a Spanish version of the Geriatric Depression
      Scale (GDS) for telephone administration. DESIGN, SETTING, AND PATIENTS: The
      original version of the GDS was translated into Spanish. A random sample of 282
      ambulatory elderly individuals was contacted by phone. Those completing the phone
      GDS (GDS-T) were asked to schedule an appointment within two weeks in which we
      collected data on demographics, physical exam, functional and mental status, and
      a face-to-face version of the GDS (GDS-P). We estimated question-to-question
      kappa statistics and the Pearson correlation coefficient between the GDS-T and
      GDS-P scores. We evaluated reliability of the GDS-T and GDS-P using the
      Cronbach's alpha coefficient. We estimated the sensitivity, specificity, and
      criterion validity of the GDS using the DSM IV criteria for depression as our
      gold standard. RESULTS: Thirty patients (11%) refused to participate. Of the
      remaining 252 patients, 169 (67%) attended the personal interview. The Cronbach's
      alpha coefficient was 0.85 for GSD-P and 0.88 for GDS-T. Sensitivity and
      specificity were 88% and 82% for GDS-P and 84% and 79% for GDS-T. The prevalence
      of depression in the group completing both scales was 12.8% using the GDS-P and
      14.9% using the GDS-T (P >.05). Among those who only completed the GDS-T, the
      prevalence was 22.7% (P <.05) suggesting that depressed patients kept their
      appointments less frequently. CONCLUSIONS: The telephone GDS had high internal
      consistency and was highly correlated with the validated personal administration
      of the scale, suggesting that it could be a valid instrument for screening of
      depression among elderly ambulatory Spanish-speaking patients. Because the
      depression rate was significantly higher among those not presenting to the
      personal evaluation, the adoption of GDS-T may help detect and plan early
      interventions in patients who otherwise would not be identified.

PMID- 11520382
TI  - Doctor discontent. A comparison of physician satisfaction in different delivery
      system settings, 1986 and 1997.
AB  - OBJECTIVE: To examine the differences in physician satisfaction associated with
      open- versus closed-model practice settings and to evaluate changes in physician
      satisfaction between 1986 and 1997. Open-model practices refer to those in which
      physicians accept patients from multiple health plans and insurers (i.e., do not
      have an exclusive arrangement with any single health plan). Closed-model
      practices refer to those wherein physicians have an exclusive relationship with a
      single health plan (i.e., staff- or group-model HMO). DESIGN: Two cross-sectional
      surveys of physicians; one conducted in 1986 (Medical Outcomes Study) and one
      conducted in 1997 (Study of Primary Care Performance in Massachusetts). SETTING:
      Primary care practices in Massachusetts. PARTICIPANTS: General internists and
      family practitioners in Massachusetts. MEASUREMENTS: Seven measures of physician
      satisfaction, including satisfaction with quality of care, the potential to
      achieve professional goals, time spent with individual patients, total earnings
      from practice, degree of personal autonomy, leisure time, and incentives for high
      quality. RESULTS: Physicians in open- versus closed-model practices differed
      significantly in several aspects of their professional satisfaction. In 1997,
      open-model physicians were less satisfied than closed-model physicians with their
      total earnings, leisure time, and incentives for high quality. Open-model
      physicians reported significantly more difficulty with authorization procedures
      and reported more denials for care. Overall, physicians in 1997 were less
      satisfied in every aspect of their professional life than 1986 physicians.
      Differences were significant in three areas: time spent with individual patients,
      autonomy, and leisure time (P < or =.05). Among open-model physicians,
      satisfaction with autonomy and time with individual patients were significantly
      lower in 1997 than 1986 (P < or =.01). Among closed-model physicians,
      satisfaction with total earnings and with potential to achieve professional goals
      were significantly lower in 1997 than in 1986 (P < or =.01). CONCLUSIONS: This
      study finds that the state of physician satisfaction in Massachusetts is
      extremely low, with the majority of physicians dissatisfied with the amount of
      time they have with individual patients, their leisure time, and their incentives
      for high quality. Satisfaction with most areas of practice declined significantly
      between 1986 and 1997. Open-model physicians were less satisfied than closed
      model physicians in most aspects of practices.

PMID- 11520383
TI  - Patient and physician satisfaction with a telephone-based anticoagulation
      service.
AB  - OBJECTIVES: To compare the satisfaction and knowledge of patients who have their
      warfarin managed by their physician or by a multidisciplinary, telephone-based
      anticoagulation service (ACS) and to assess referring physicians' satisfaction
      with the ACS. DESIGN AND PARTICIPANTS: We surveyed 300 patients taking warfarin
      (mean age 73 years): 150 at health centers randomized to have access to an ACS,
      and 150 at control health centers without ACS access. We also surveyed 17
      physicians who refer patients to the ACS. SETTING: Eight outpatient health
      centers in Missouri and Southern Illinois. MEASUREMENTS: We asked patients about
      the timeliness of international normalized ratio (INR) monitoring, perceived
      safety of warfarin, overall satisfaction with their warfarin management, and
      knowledge of what a high INR meant. We asked physicians at ACS-available health
      centers how many minutes they saved per INR by referring patients to the ACS,
      their satisfaction with the ACS, and their willingness to recommend the ACS to a
      colleague. MAIN RESULTS: As compared with patients at control health centers,
      patients at ACS-available health centers were more satisfied with the timeliness
      of getting blood test results (mean 4.31 vs 4.03, P =.02), were more likely to
      know what a safe INR value was (45% vs 15%, P =.001), and felt safer taking
      warfarin (mean 5.7 vs 5.2, P =.04). Physicians reported that using the ACS saved,
      on average, four minutes of their time and 13 minutes of their staff's time, per
      INR. All physicians recommended use of the ACS to a colleague and were highly
      satisfied with the ACS. CONCLUSIONS: A telephone-based ACS can be endorsed by
      primary-care physicians and improve patients' satisfaction with and knowledge
      about their antithrombotic therapy.

PMID- 11520384
TI  - The computer-based lecture.
AB  - Advancing computer technology, cost-containment pressures, and desire to make
      innovative improvements in medical education argue for moving learning resources
      to the computer. A reasonable target for such a strategy is the traditional
      clinical lecture. The purpose of the lecture, the advantages and disadvantages of
      "live" versus computer-based lectures, and the technical options in computerizing
      the lecture deserve attention in developing a cost-effective, complementary
      learning strategy that preserves the teacher-learner relationship. Based on a
      literature review of the traditional clinical lecture, we build on the strengths
      of the lecture format and discuss strategies for converting the lecture to a
      computer-based learning presentation.

PMID- 11520385
TI  - Impact of interpreter services on delivery of health care to limited-English
      proficient patients.
AB  - OBJECTIVE: To determine whether professional interpreter services increase the
      delivery of health care to limited-English-proficient patients. DESIGN: Two-year
      retrospective cohort study during which professional interpreter services for
      Portuguese and Spanish-speaking patients were instituted between years one and
      two. Preventive and clinical service information was extracted from computerized
      medical records. SETTING: A large HMO in New England. PARTICIPANTS: A total of
      4,380 adults continuously enrolled in a staff model health maintenance
      organization for the two years of the study, who either used the comprehensive
      interpreter services (interpreter service group [ISG]; N = 327) or were randomly
      selected into a 10% comparison group of all other eligible adults (comparison
      group [CG]; N = 4,053). MEASUREMENTS AND MAIN RESULTS: The measures were change
      in receipt of clinical services and preventive service use. Clinical service use
      and receipt of preventive services increased in both groups from year one to year
      two. Clinical service use increased significantly in the ISG compared to the CG
      for office visits (1.80 vs. 0.70; P <.01), prescriptions written (1.76 vs 0.53; P
      <.01), and prescriptions filled (2.33 vs. 0.86; P<.01). Rectal examinations
      increased significantly more in the ISG compared to the CG (0.26 vs. 0.02; P
      =.05) and disparities in rates of fecal occult blood testing, rectal exams, and
      flu immunization between Portuguese and Spanish-speaking patients and a
      comparison group were significantly reduced after the implementation of
      professional interpreter services. CONCLUSION: Professional interpreter services
      can increase delivery of health care to limited-English-speaking patients.

PMID- 11520386
TI  - Does "mainstreaming" guarantee access to care for medicaid recipients with
      asthma?
AB  - OBJECTIVE: Recent reforms in the federal Medicaid program have attempted to
      integrate beneficiaries into the mainstream by providing them with managed care
      options. However, the effects of mainstreaming have not been systematically
      evaluated. DESIGN: Cross-sectional survey. SETTING/PARTICIPANTS: A sample of 478
      adult, nonelderly asthmatics followed by a large Northern California medical
      group. MEASUREMENTS AND MAIN RESULTS: We examined differences in self-reported
      access by insurance status. Compared to patients with other forms of insurance,
      patients covered by the state's Medicaid program (Medi-Cal) were more likely to
      report access problems for asthma-related care, including difficulties in
      reaching a health care provider by telephone, obtaining a clinic appointment, and
      obtaining asthma medication. Adjusting for relevant clinical and sociodemographic
      variables, Medi-Cal patients were more likely to report at least one access
      problem compared to non-Medi-Cal patients (adjusted odds ratio [AOR], 3.34; 95%
      confidence interval [CI], 1.43 to 7.80). Patients reporting at least one access
      problem were also more likely to have made at least one asthma-related emergency
      department visit within the past year (AOR, 4.84; 95% CI, 2.41 to 9.72). Reported
      barriers to care did not translate into reduced patient satisfaction.
      CONCLUSIONS: Within this population of Medicaid patients, the provision of health
      insurance and care within the mainstream of an integrated health system was no
      guarantee of equal access as perceived by the patients themselves.

PMID- 11520387
TI  - Using survival curve comparisons to inform patient decision making can a practice
      exercise improve understanding?
AB  - BACKGROUND: Patients often face medical decisions that involve outcomes that
      occur and change over time. Survival curves are a promising communication tool
      for patient decision support because they present information about the
      probability of an outcome over time in a simple graphic format. However, previous
      studies of survival curves did not measure comprehension, used face-to-face
      explanations, and focused on a VA population. METHODS: In this study, 246
      individuals awaiting jury duty at the Philadelphia County Courthouse were
      randomized to receive one of two questionnaires. The control group received a
      questionnaire describing two hypothetical treatments and a graph with two
      survival curves showing the outcomes of each treatment. The practice group
      received the same questionnaire preceded by a practice exercise asking questions
      about a graph containing a single curve. Subjects' ability to interpret survival
      from a curve and ability to calculate change in survival over time were measured.
      RESULTS: Understanding of survival at a single point in time from a graph
      containing two survival curves was high overall, and was improved by the use of a
      single curve practice exercise. With a practice exercise, subjects were over 80%
      accurate in interpreting survival at a single point in time. Understanding of
      changes in survival over time was lower overall, and was not improved by the use
      of a practice exercise. With or without a practice exercise, subjects were only
      55% accurate in calculating changes in survival. CONCLUSION: The majority of the
      general public can interpret survival at a point in time from self-administered
      survival curves. This understanding is improved by a single curve practice
      exercise. However, a significant proportion of the general public cannot
      calculate change in survival over time. Further research is necessary to
      determine the effectiveness of survival curves in improving risk communication
      and patient decision making.

PMID- 11520388
TI  - The challenge of problem residents.
AB  - Internal medicine residency training is demanding and residents can experience a
      wide variety of professional and personal difficulties. Residency programs
      everywhere have had and will continue to have problem residents. Training
      programs should be equipped to effectively identify and manage residents who
      experience problems. Previous articles that have been published on the topic of
      problem residents primarily addressed concerns such as impairment due to
      depression and substance abuse. The content of this article is derived from a
      comprehensive review of the literature as well as other data sources such as
      interviews with program directors and workshops at national professional
      meetings. This article focuses primarily on four issues related to problem
      residents: their identification, underlying causes, management, and prevention.
      The study attempts to be evidence-based, wherever possible, highlighting what is
      known. Recommendations based on the synthesis of the data are also made. Future
      ongoing studies of problem residents will improve our understanding of the
      matters involved, and may ultimately lead to improved outcomes for these
      trainees.

PMID- 11520389
TI  - The role of culture and language in determining best practices.

PMID- 11520390
TI  - Physician discontent: a barometer of change and need for intervention.

PMID- 11520394
TI  - March of Dimes commitment to solving the problem of prematurity.

PMID- 11520391
TI  - Evaluation of residents: challenges and opportunities.

PMID- 11520395
TI  - Overview: new perspectives on the stubborn challenge of preterm birth.

PMID- 11520396
TI  - Preterm delivery: a public health perspective.

PMID- 11520397
TI  - Stress, infection and preterm birth: a biobehavioural perspective.
AB  - Preterm birth is currently the most important problem in maternal-child health in
      the United States. Epidemiological studies have suggested that two factors,
      maternal stress and maternal urogenital tract infection, are significantly and
      independently associated with an increased risk of spontaneous preterm birth.
      These factors are also more prevalent in the population of sociodemographically
      disadvantaged women who are at increased risk for preterm birth. Studies of the
      physiology of parturition suggest that neuroendocrine and immune processes play
      important roles in the physiology and pathophysiology of normal and preterm
      parturition. However, not all women with high levels of stress and/or infection
      deliver preterm, and little is understood about factors that modulate
      susceptibility to pathophysiological events of the endocrine and immune systems
      in pregnancy. We present here a comprehensive, biobehavioural model of maternal
      stress and spontaneous preterm delivery. According to this model, chronic
      maternal stress is a significant and independent risk factor for preterm birth.
      The effects of maternal stress on preterm birth may be mediated through
      biological and/or behavioural mechanisms. We propose that maternal stress may act
      via one or both of two physiological pathways: (a) a neuroendocrine pathway,
      wherein maternal stress may ultimately result in premature and/or greater degree
      of activation of the maternal-placental-fetal endocrine systems that promote
      parturition; and (b) an immune/inflammatory pathway, wherein maternal stress may
      modulate characteristics of systemic and local (placental-decidual) immunity to
      increase susceptibility to intrauterine and fetal infectious-inflammatory
      processes and thereby promote parturition through pro-inflammatory mechanisms. We
      suggest that placental corticotropin-releasing hormone may play a key role in
      orchestrating the effects of endocrine and inflammatory/immune processes on
      preterm birth. Moreover, because neuroendocrine and immune processes extensively
      cross-regulate one another, we further posit that exposure to both high levels of
      chronic stress and infectious pathogens in pregnancy may produce an interaction
      and multiplicative effect in terms of their combined risk for preterm birth.
      Finally, we hypothesise that the effects of maternal stress are modulated by the
      nature, duration and timing of occurrence of stress during gestation. A
      discussion of the components of this model, including a theoretical rationale and
      review of the available empirical evidence, is presented. A major strength of
      this biobehavioural perspective is the ability to explore new questions and to do
      so in a manner that is more comprehensive than has been previously attempted. We
      expect findings from this line of proposed research to improve our present state
      of knowledge about obstetric risk assessment for preterm birth by determining the
      characteristics of pregnant women who are especially susceptible to stress and/or
      infection, and to broaden our understanding of biological (endocrine, immune, and
      endocrine-immune interactions) mechanisms that may translate social adversity
      during pregnancy into pathophysiology, thereby suggesting intervention
      strategies.

PMID- 11520398
TI  - Stress and preterm delivery: a conceptual framework.
AB  - Numerous epidemiological studies of various kinds of stress and preterm delivery
      have produced either negative or weakly positive results. Those inconclusive
      findings could be either because of the absence of an association or because of
      recognised methodological problems that may have masked an association. The
      biological plausibility of the stress hypothesis provides one rationale for
      continuing stress research, using better study designs. To further this agenda,
      we propose an epidemiological model, based on the classic "host, environment,
      agent" triangle of epidemiological causality. The host is the individual woman,
      more or less susceptible to stressor-induced pathology. The environment includes
      the social and cultural conditions that are ongoing stressors as well as social
      and cultural modifiers of stress e.g. those factors that may influence how a
      particular stressor is experienced or what the physical response to it may be.
      The agent is the immediate emotional or physical stressor requiring her response.
      We draw from recent literature, published principally since 1990, to illustrate
      this model. This epidemiological model posits that whether the individual is
      overwhelmed by stressors depends not only on the strength of the agents but also
      upon host susceptibility to stress, as well as the background level of acute,
      environmental and contextual stressors, and the moderating influence of host,
      environmental and contextual resources for handling stress. Future research needs
      to be based on stress hypotheses that include all sides of the triangle, data
      collection instruments that adequately capture relevant stressors and stress
      responses, and analytical techniques capable of handling complex, multilevel
      relationships.

PMID- 11520399
TI  - The role of infection in preterm labour and delivery.

PMID- 11520400
TI  - Preterm labour and delivery: a genetic predisposition.
AB  - Preterm delivery (PTD) complicates as many as 10% of pregnancies in the United
      States. Moreover, prematurity accounts for more than 70% of the consequent
      neonatal and infantile morbidity and mortality. Serious long-term complications
      include cerebral palsy, respiratory disease, blindness and deafness. Despite
      substantial basic scientific, translational and clinical investigation in recent
      years, the PTD rate (10%) and the low birthweight rate (7%) remain largely
      unchanged. Indeed, the very aetiology and pathophysiology of PTD remain unknown
      in most cases. In short, PTD continues to constitute a major clinical and public
      health challenge of the highest order, a circumstance further compounded by the
      controversy surrounding the efficacy of current therapeutic regimens. In an
      effort to address the relevant knowledge gap, we put forth the hypothesis that
      PTD results, at least in part, from a genetic predisposition. Evidence supporting
      the hypothesis that certain women have a genetic predisposition to deliver
      preterm is growing. Moreover, the discovery of a gene mutation predisposing to
      PTD would constitute a major breakthrough for future research into the biology,
      prediction, and therapy of preterm labour. Presented here is a discussion of the
      evidence to support a genetic predisposition to PTD, molecular techniques
      proposed to study the genetics of preterm labour, and plausible candidate genes
      that warrant further investigation.

PMID- 11520402
TI  - Risk stratification and pathological mechanisms in preterm delivery.
AB  - The delivery of infants before 37 weeks gestation is a leading cause of perinatal
      mortality and morbidity in the United States. Traditional methods of predicting
      women at risk relying on obstetric history or premonitory symptoms (detected
      clinically or by tocodynamometry) are neither sensitive nor specific. Recent
      approaches to predicting preterm delivery have included sonographic measurement
      of cervical length and various biochemical assays. Although more sensitive than
      traditional methods, none of these alone exhibits sufficient accuracy to warrant
      widespread use. We contend that the failure of current approaches to predicting
      preterm delivery reflects an inadequate understanding of the underlying
      pathogenesis. Clinical and experimental evidence support the concept that most
      cases of preterm delivery reflect four pathogenic processes, which share a common
      final biological pathway leading to uterine contractions and cervical changes
      with or without premature rupture of membranes. These pathogeneses are: (1)
      activation of the maternal or fetal hypothalamic-pituitary-adrenal axis; (2)
      decidual-chorioamniotic or systemic inflammation; (3) decidual haemorrhage (i.e.
      abruption); and (4) pathological distention of the uterus. Our research seeks to
      combine the most useful biophysical and biochemical markers of such processes
      with optimal clinical and epidemiological predictors into a composite, easily
      applied risk tool. This integrated approach has the potential to identify at-risk
      asymptomatic patients with high sensitivity, specificity, and positive and
      negative predictive values, and also to ascertain underlying pathogenic processes
      that can lead to targeted therapy. To accomplish these goals, we employ logistic
      regression and artificial neural network models to assess and apply the
      appropriate weight to markers associated with each of the above pathogenic
      pathways, in addition to markers of the final common pathway leading to fetal
      membrane rupture, cervical extracellular matrix degradation, and myometrial
      activation. By combining these markers, we expect ultimately to produce a
      predictive model that is more robust than any existing method, and that
      identifies the relative contribution of each pathogenic process. Further analysis
      of this model using a neural network will enable us to identify asymptomatic
      patients destined to deliver preterm with high sensitivity, specificity, positive
      and negative predictive values, and to assess the relative contribution of each
      of the four distinct pathogeneses to this preterm delivery risk.

PMID- 11520401
TI  - Molecular epidemiology of preterm delivery: methodology and challenges.
AB  - Preterm delivery (PTD) appears to be a complex trait determined by both genetic
      and environmental factors. Few studies have examined genetic influence on PTD.
      The overall goal of our study is to examine major candidate genes of PTD and to
      test gene-environment interactions. Our study includes 500 preterm trios,
      including 500 preterm babies and their parents and 500 maternal age-matched term
      controls. We will perform the transmission/disequilibrium test (TDT) on candidate
      genes thought to be important in each of the four biological pathways of PTD: (1)
      decidual chorioamionotic inflammation: interleukin 1 (IL-1), IL-6, and tumour
      necrosis factor (TNF); (2) maternal and fetal stress: corticotropin-releasing
      hormone (CRH); (3) uteroplacental vascular lesions: methylenetereahydrofolate
      reductase (MTHFR); and (4) susceptibility to environmental toxins: GSTM1, GSTT1,
      CYP1A1, CYP2D6, CYP2E1, NAT2, NQO1, ALDH2, and EPHX. We will also perform
      standard case-control analyses on the 500 preterm cases and 500 term controls to
      examine gene-environment interactions. The major environmental, nutritional and
      social factors as well as clinical variables known or suspected to be associated
      with PTD will be used to test for gene-environment interactions. This study
      integrates epidemiological and clinical data as well as genetic markers along
      major pathogenic pathways of PTD. The findings from this study should improve our
      understanding of genetic influences on PTD and gene-environment interactions.

PMID- 11520403
TI  - Identification of biological/biochemical marker(s) for preterm delivery.
AB  - Fetal and neonatal mortality and morbidity rates are strongly associated with
      gestational age for delivery: the risk for poor outcome increases as gestational
      age decreases. Attempts to predict preterm delivery (PTD, spontaneous delivery
      before 37 weeks' gestation) have been largely unsuccessful, and rates of PTD have
      not improved in recent decades. More recently, the reported associations between
      infections in pregnancy and PTD suggest preventive initiatives that could be
      taken. The overall objective of the current study is to assess whether specific
      markers of infection (primarily interleukin (IL) 1beta, tumour necrosis factor
      (TNF) alpha, IL-6, and IL-10) obtained from maternal blood during pregnancy,
      alone or in combination with other risk factors for PTD, permit identification of
      women at risk for spontaneous PTD. To achieve this objective, data are obtained
      from two Danish prospective cohort studies involving serial collection of
      maternal blood samples, newborn cord blood samples, and relevant confounders and
      other risk factors for PTD. The first study consists of a completed Danish
      regional cohort of 3000 pregnant women enrolled in a study of microbiological
      causes of PTD, upon which a nested case-control study of PTD in 84 cases and 400
      controls has been performed. The second study is a nested case-control study of
      675 PTD cases (equally divided into three gestational age categories of 24-29
      weeks' gestation, 30-33 weeks' gestation, and 34-36 weeks' gestation) and 675
      controls drawn from the ongoing Danish National Birth Cohort study of 100 000
      pregnant women enrolled during 1997-2001. The second study will provide the
      opportunity to refine and retest hypotheses from the first study, as well as to
      explore new hypotheses. Our preliminary work suggests that a single predictive
      marker effectively accounting for a large proportion of PTD is unlikely to be
      found. Rather, a search for multiple markers indicative of the multifactorial
      aetiology of PTD is likely to be more successful. Knowledge gained from the
      proposed studies will be implemented in a third, clinical intervention study
      against PTD. The first phase of the clinical intervention study will be to
      establish a risk-assessment model based on the "best" combination of
      biological/biochemical measures and other factors associated with PTD in order to
      identify pregnant women at very high risk of PTD. The second phase will be to
      apply an intervention model of tailored obstetric care to the very high-risk
      pregnant women for PTD identified in phase one. The intervention will be carried
      out against each specific risk factor associated with PTD identified for the
      individual. The aim is to reduce the risk for PTD attributed to the combination
      of risk factors included in the clinical intervention study.

PMID- 11520404
TI  - Socio-economic disparities in preterm birth: causal pathways and mechanisms.
AB  - Preterm birth is the leading cause of infant mortality in industrialised
      societies. Its incidence is greatly increased among the socially disadvantaged,
      but the reasons for this excess are unclear and have been relatively unexplored.
      We hypothesise two distinct sets of causal pathways and mechanisms that may
      explain social disparities in preterm birth. The first set involves chronic and
      acute psychosocial stressors, psychological distress caused by those stressors,
      increased secretion of placental corticotropin releasing hormone (CRH), changes
      in sexual behaviours or enhanced susceptibility to bacterial vaginosis and
      chorioamnionitis, cigarette smoking or cocaine use, and decidual vasculopathy.
      The second hypothesised pathway is a gene-environment interaction based on a
      highly prevalent mutation in the gene for methylenetetrahydrofolate reductase
      (MTHFR), combined with low folate intake from the diet and from prenatal vitamin
      supplements, consequent hyperhomocysteinemia, and decidual vasculopathy. We
      propose to test these hypothesised pathways and mechanisms in a nested case
      control study within a prospectively recruited and followed cohort of pregnant
      women with singleton pregnancies who deliver at one of four Montreal hospitals
      that serve an ethnically and socio-economically diverse population. Following
      recruitment during the late first or early second trimester, participating women
      are seen at 24-26 weeks, when a research nurse obtains a detailed medical and
      obstetric history; administers several scales to assess chronic and acute
      stressors and psychological function; obtains blood samples for CRH, red blood
      cell and plasma folate, homocysteine, and DNA for the MTHFR mutation; and
      performs a digital and speculum examination to measure cervical length and
      vaginal pH and to obtain swabs for bacterial vaginosis and fetal fibronectin.
      After delivery, each case (delivery at < 37 completed weeks following spontaneous
      onset of labour or prelabour rupture of membranes) and two controls are selected
      for placental pathological examination, hair analysis of cotinine, cocaine, and
      benzoylecgonine, and analysis of stored blood and vaginal specimens. Statistical
      analysis will be based on multiple logistic regression and structural equation
      modelling, with sequential construction of models of potential aetiological
      determinants and covariates to test the hypothesised causal pathways and
      mechanisms. The research we propose should improve understanding of the factors
      and processes that mediate social disparities in preterm birth. This improved
      understanding should help not only in developing strategies to reduce the
      disparities but also in suggesting preventive interventions applicable across the
      entire socio-economic spectrum.

PMID- 11520405
TI  - Maternal experiences of racism and violence as predictors of preterm birth:
      rationale and study design.
AB  - Chronic psychological stress may raise the risk of preterm delivery by raising
      levels of placental corticotropin-releasing hormone (CRH). Women who have been
      the targets of racism or personal violence may be at particularly high risk of
      preterm delivery. The aims of this study are to examine the extent to which: (1)
      maternal experiences of racism or violence in childhood, adulthood, or pregnancy
      are associated with the risk of preterm birth; (2) CRH levels are prospectively
      associated with risk of preterm birth; and (3) CRH levels are associated with
      past and current maternal experiences of racism or violence. We have begun to
      examine these questions among women enrolled in Project Viva, a Boston-based
      longitudinal study of 6000 pregnant women and their children.

PMID- 11520406
TI  - Pregnancy outcomes and community health: the POUCH study of preterm delivery.
AB  - In light of the social/ethnic disparity in preterm delivery (PTD) rates, the
      Pregnancy Outcomes and Community Health (POUCH) Study takes a broad view of the
      determinants of PTD by attempting to link underlying biological and psychosocial
      factors. The relationships between placental pathology, maternal biomarkers, and
      antecedent psychosocial factors are evaluated in three hypothesised pathways of
      PTD - one characterised primarily by infection, one by maternal vascular disease,
      and one by premature elevations in corticotropin releasing hormone in the absence
      of histological evidence of placental pathology. Within each pathway, an emphasis
      is placed on understanding the roles of stress and of maternal serum alpha
      fetoprotein, an early biomarker associated with PTD. The POUCH Study enrolls
      pregnant women from five Michigan communities. Information about these women and
      their environments is gathered through detailed interviews and collection of
      biological samples including hair, urine, saliva, blood, vaginal fluid, and
      vaginal smear at 15-26 weeks of gestation. We have chosen to focus on the second
      trimester--a time when pathological processes may have evolved to a detectable
      stage, but generally before the onset of biological changes that accompany
      labour. This focus is consistent with the long-range goal of early
      detection/intervention and prevention of PTD.

PMID- 11520407
TI  - Preterm birth research: from disillusion to the search for new mechanisms.
AB  - No intervention has been shown to decrease the rate of preterm birth. There was
      thus a need for a new research agenda. The new emphasis is on social and
      biological mechanisms, including the impact on stress of racism and poverty, and
      gene-environment interactions. New markers are also under study, and pertain
      mostly to infection and inflammation. The impact on preterm birth of broad
      contextual factors, such as universal social protection, will need to be explored
      further. The recent trends toward increased rates of preterm births deserve much
      attention. New policies and interventions to decrease medically indicated preterm
      births should be urgently developed and evaluated. The failure to prevent preterm
      deliveries has been so disappointing that there is a risk that high rates of
      preterm births will be seen as unavoidable. The research programme launched by
      March of Dimes is a timely effort to foster new enthusiasm, to test new ideas and
      to generate new hypotheses.

PMID- 11520408
TI  - Paediatric transfusion.
AB  - Paediatric transfusion encompasses a wide range of clinical circumstances
      including the consideration of maternal antibodies, the changing nature of the
      transfusion recipient with respect to growth and development, and the management
      of inherited conditions which if optimally treated in early life may have
      problems which are delayed or less severe in adult life. Whilst the transfusion
      of adults and children has much in common, a child cannot be considered as a
      scaled down adult; there are many important differences. Developmental changes
      are most marked in the neonate and, together with the fact that their antibodies
      are maternally derived, this population provide some of the most striking
      challenges. The increased use of intra uterine transfusion adds an extra
      dimension here. A particular paediatric concern is the long-term consequences of
      transfusion. It is to be hoped that paediatric transfusion recipients will live
      long enough that any potential problems will manifest themselves, thus the aim
      must be to minimize transfusion risks.

PMID- 11520409
TI  - Variant Creutzfeldt-Jakob disease in Australian blood donors: estimation of risk
      and the impact of deferral strategies.
AB  - BACKGROUND AND OBJECTIVES: In Australia, a policy of deferring donors who have
      lived in the UK for longer than 6 months between 1980 and 1996 has been
      instituted to reduce the theoretical risk of transmitting variant Creutzfeldt
      Jakob disease (vCJD) through the blood supply. The objective of this report was
      to refine estimates of the possible risks and benefits of donor-deferral
      strategies that are aimed at avoiding transmission of vCJD. MATERIALS AND
      METHODS: Estimates of the effect of donor deferral on the blood supply in
      Australia were based on a 1998 survey of blood donors. The number of donations
      from donors potentially infected with vCJD and excluded by donor deferral was
      estimated based on published estimates of the size of the vCJD epidemic in the UK
      and assuming that the risk of vCJD in Australian blood donors was proportional to
      the time lived in the UK between 1980 and 1996. The possible increased number of
      blood donations that were infected with human immunodeficiency virus (HIV),
      hepatitis C virus (HCV) or hepatitis B virus (HBV) and made during a window
      period (as a result of increased donations from first-time donors) was estimated
      using published methods. RESULTS: A strategy of deferring donations in Australia
      from people who have lived in the UK for 6 months or longer, between 1980 and
      1996, was estimated to result in exclusion of 5.3% of all blood donations,
      corresponding to 50 100 donations in 1998. It was estimated that the annual
      number of blood donations made by donors potentially infected with vCJD is 1.15
      (range 0.02--31.1, based on the uncertainty in the UK prevalence estimate). Donor
      deferral was estimated to remove 0.92 (range 0.02--25.1) of these donations.
      Replacement of 33%, 50% and 100% of excluded donations by donations from first
      time donors, was estimated to result in an increase of 0.0010, 0.0019 and 0.0044,
      respectively, of HIV-infected donations per year donated during the window
      period; in an increase of 0.021, 0.038 and 0.089, respectively, of HCV-infected
      donations per year; and in an increase of 0.18, 0.33 and 0.76, respectively, of
      HBV-infected donations per year. CONCLUSIONS: The large uncertainties involved in
      these analyses mean that estimates must be interpreted cautiously, but the data
      does suggest that donor deferral may exclude more donations from donors
      potentially infected with vCJD than the corresponding increase, caused by donor
      replacement, of window-period donations possibly infected with HIV, HCV or HBV.

PMID- 11520410
TI  - Validation of the NucliSens Extractor in combination with the hepatitis C virus
      Cobas Amplicor 2.0 assay in four laboratories in the Netherlands utilizing
      nucleic acid amplification technology for blood screening.
AB  - BACKGROUND AND OBJECTIVES: Since July 1 1999, four laboratories in the
      Netherlands have been routinely screening plasma minipools for the release of
      labile blood components utilizing hepatitis C virus nucleic acid amplification
      technology (HCV NAT). This report describes the performance evaluation of the HCV
      NAT method and the quality control results obtained during 6 months of routine
      screening. MATERIALS AND METHODS: Plasma minipools of 48 donations were prepared
      on a Tecan Genesis robot. HCV RNA was isolated from 2 ml of plasma by using the
      NucliSens Extractor and amplified and detected with the Cobas HCV Amplicor 2.0
      test system. For validation of the test system the laboratories used viral
      quality control (VQC) reagents of CLB. RESULTS: Initial robustness experiments
      demonstrated consistent detection of PeliSpy HCV RNA samples of 140 genome
      equivalents/ml (geq/ml) in each station of the installed Nuclisens Extractors.
      Further 'stress' tests with a highly viraemic sample of approximately 5 x 10(6)
      geq/ml did not contaminate negative samples processed on all Extractor stations
      in subsequent runs. In the validation period prior to July 1999, 1021 pools were
      tested with the following performance characteristics: 0.1%, initially false
      reactive; 0.89%, failure of internal control detection; 0.97%, no eluate
      generated by the Extractor; and 100% reactivity of the PeliSpy 140 geq/ml control
      in 176 Extractor runs and a 98% reactivity rate of the PeliSpy 38 geq/ml control
      in 102 test runs. By testing the PeliCheck HCV RNA genotype 1 dilution panels 49
      times, an overall 95% detection limit of 30 geq/ml ( approximately 8 IU/ml) and a
      50% detection limit of 5 geq/ml was found by the four laboratories. In the first
      6 months of routine screening, the minimum requirement for invalid results (2%)
      was exceeded with some batches of silica and NucliSens Extractor cartridges. From
      November 1999 to February 2000, the manufacturer (Organon Teknika) improved the
      protocol for silica absorption of the Nuclisens Extractor -- the cartridge design
      as well as the software of the Extractor. During the next 6 months of observation
      in 2000, the percentages of false initial reactives and invalids were 0.05% and
      1.4%, respectively, in 8962 pools tested. Of these invalid results, 0.74% and
      0.66% were caused by Extractor failure and negative internal control signals,
      respectively. The PeliSpy HCV RNA 'stop or go' run control of 140 geq/ml was 100%
      reactive, but invalid in 16/1375 (1.2%) of cases. The PeliSpy run control of 38
      geq/ml for monitoring sensitivity of reagent batches was reactive in 95% of 123
      samples tested. CONCLUSIONS: Each of the four HCV NAT laboratories in the
      Netherlands have achieved similar detection limits that are well below the
      sensitivity requirements of the regulatory bodies. After improvement of the
      NucliSens Extractor procedure, the robustness of the test system has proved to be
      acceptable for routine screening and timely release of all labile blood
      components.

PMID- 11520411
TI  - Age of blood in inventory at a large tertiary care hospital.
AB  - BACKGROUND AND OBJECTIVES: This major tertiary care centre transfers over 1000
      red cell units monthly. Units are rotated as part of inventory management to
      ensure minimum wastage. In 1998, the expiration date of AS3 red cells was
      extended from 35 to 42 days, potentially affecting inventory. MATERIALS AND
      METHODS: The average age of the red cell units in inventory on any given day was
      evaluated to determine whether the extended expiration date would affect blood
      availability and to determine the feasibility of using blood at different ages
      for various purposes. Over a 6-month duration, 20 days were selected for review:
      units were categorized according to ABO group and Rh type and then analysed for
      age within certain categories. RESULTS: The average age of the blood in inventory
      was 1 to 2 weeks. The probability of having units less than 1-week old was
      highest for Group O and zero for Group B Rh(+) and Group AB Rh(+). More than 60%
      of the O Rh(-) blood was older than 28 days. CONCLUSION: The age of units in
      inventory varies with respect to ABO group, Rh type and weekday. In practice, the
      stock rarely reaches 42 days of age. Future studies on the effects of age of
      blood on patient outcome must consider the logistics of supply and the
      availability of blood of each group. Transfusion of large numbers of units of the
      same age and of a specific blood group and type may not always be possible.

PMID- 11520412
TI  - Bradykinin production during donor plasmapheresis procedures.
AB  - BACKGROUND AND OBJECTIVES: Extracorporeal circuits made of artificial substances
      may induce blood cells and humoral activation. Negatively charged surfaces may
      activate Factor XII and the prekallikrein-kinin cascade, resulting in bradykinin
      (BK) production. BK has been considered to be involved in severe hypotensive
      reactions occurring during therapeutic apheresis in patients taking angiotensin
      converting enzyme (ACE) inhibitors or in those receiving platelet transfusion. In
      this study we investigated BK production during donor plasmapheresis procedures.
      PATIENTS AND METHODS: Eighteen volunteer donors entered the study protocol. Nine
      of them were taking ACE inhibitors. Their blood pressure (BP) was monitored both
      pre- and post-apheresis, and BK determination was carried out using a competitive
      enzyme immunoassay (EIA), in plasma samples collected both during and at
      completion of the procedure. In addition, a limited number of thawed plasma units
      were checked for BK. RESULTS: No side-effects were observed during the
      procedures. However, donors taking ACE inhibitors showed a higher variation of
      their systolic BP compared to those who were not taking ACE inhibitors, while
      diastolic BP percentage variations did not differ significantly between the two
      groups. The BK concentration was considerably higher in donors taking ACE
      inhibitors: 183 +/- 26 versus 82 +/- 6 ng/ml (P < 0.0001) after the first
      collection cycle and 142 +/- 20 versus 65 +/- 11 ng/ml (P < 0.0001) in the final
      samples. BK was also detected, at a lower concentration (15 ng/ml), in one out of
      four thawed plasma units obtained from donors taking ACE inhibitors and at 1
      ng/ml in one out of two thawed plasma units from the control group. CONCLUSION:
      Donors taking ACE inhibitors and undergoing plasmapheresis showed higher levels
      of BK compared to the control group. Furthermore, the detection of BK in plasma
      units after a freeze-thaw procedure might explain the sudden hypotensive reaction
      occurring during therapeutic plasma exchange when plasmapheresis units are
      adopted as substitution fluids. Further investigations are needed to assess the
      real clinical importance of the presence of BK in plasma units.

PMID- 11520413
TI  - Preparation and properties of an alpha-1-protease inhibitor concentrate with high
      specific activity.
AB  - BACKGROUND AND OBJECTIVES: Because the current demand for alpha-1-protease
      inhibitor (A1PI) exceeds the available supply, we aimed to develop a process for
      purification of A1PI from plasma which would achieve the highest possible degree
      of purity, specific activity and yield. MATERIALS AND METHODS: A1PI was purified
      from Cohn fraction IV-1,4 using ethanol precipitation and Q-Sepharose
      chromatography. Ceramic hydroxyapatite chromatography was used as a final
      purification step. Two independent virus-inactivation procedures (chemical and
      vapour heating) were applied. RESULTS: The resulting A1PI had an unprecedented
      high specific activity. In addition, the process led to the discovery of a new
      isoform of A1PI in isoelectric focusing gels. CONCLUSION: The high specific
      activity of the A1PI preparation achieved with this process should allow a
      reduction of the A1PI total protein load necessary to achieve clinically relevant
      effects.

PMID- 11520414
TI  - Sources of preventable errors related to transfusion.
AB  - BACKGROUND AND OBJECTIVES: Transfusion errors always remain under-reported owing
      to a lack of awareness about transfusion-related adverse events among the
      hospital staff and an inadequate feedback system in most of the transfusion
      centres. This article reports the results obtained from a study carried out to
      investigate the sources and types of errors in our tertiary care hospital.
      MATERIALS AND METHODS: The errors reported by the blood bank staff (i.e.
      reception counter clerical and technical staff) and the residents in charge of
      the patient, were studied over a period of 1 year (from May 1998 to April 1999)
      and classified based on the site of occurrence. RESULTS: A total of 123 errors
      were detected over the 1-year study period. Of these 123 errors, 107 (86.99%)
      occurred outside the blood bank and 16 (13%) in the blood bank. CONCLUSION:
      Errors occur most frequently outside the blood bank, and the bedside of the
      patient is the main location.

PMID- 11520415
TI  - Primary refractoriness to platelet transfusion caused by Nak(a) antibody alone.
AB  - BACKGROUND AND OBJECTIVES: Anti-Nak(a), a platelet-specific antibody,
      occasionally causes platelet-transfusion refractoriness (PTR) together with human
      leucocyte antigen (HLA) antibodies. Anti-Nak(a) usually appears after frequent
      platelet transfusions or pregnancy. We report the first case of PTR caused by
      anti-Nak(a) alone. MATERIALS AND METHODS: A 19-year-old male patient with
      testicular tumour showed PTR when receiving his first transfusion of platelets.
      Screening for platelet antigens and platelet antibodies revealed that he had type
      I CD36 (Nak(a)) deficiency and that anti-Nak(a), but not anti-HLA, was present
      before he received his first transfusion. RESULTS: The transfusion of Nak(a)
      negative, but HLA non-selected, platelets was effective in raising the platelet
      count. CONCLUSION: Clinically significant Nak(a) antibody was present as
      naturally occurring antibody in a platelet glycoprotein IV (CD36)-negative non
      transfused male patient.

PMID- 11520416
TI  - Rapid detection of antibodies to immunoglobulin A molecules by using the particle
      gel immunoassay.
AB  - BACKGROUND AND OBJECTIVES: Antibodies to immunoglobulin A (IgA) molecules are
      thought to be frequently responsible for anaphylactic reactions in transfusion
      medicine, but practical tests for the detection of antibodies to IgA are not yet
      available. MATERIAL AND METHODS: Red, high-density polystyrene beads were coated
      with purified IgA molecules and then used to test serum samples collected from
      unselected healthy blood donors (n = 105) and patients with common variable
      immunodeficiency and/or IgA deficiency (n = 44). For testing, the standard gel
      agglutination technique (ID-Micro Typing System) was employed. RESULTS: None of
      the normal serum samples were reactive with IgA-coated beads and samples from
      only 10 patients were positive (titre range 1 : 2 to 1 : 256). Only one out of
      all patients studied had a history of an anaphylactic reaction and this was
      related to the administration of Rh(D) prophylaxis (anti-D immunoglobulin). The
      beads did not show non-specific agglutination and could be used repeatedly for
      longer than 6 months. The results were reproducible in all patients tested.
      CONCLUSION: The new test allows a specific and rapid detection of antibodies to
      IgA molecules. In order to evaluate the clinical relevance of the test, analysis
      is required of a wider range of antibodies that produce anaphylactic reactions.

PMID- 11520417
TI  - Polymerase chain reaction with sequence-specific primers-based genotyping of the
      human Dombrock blood group DO1 and DO2 alleles and the DO gene frequencies in
      Chinese blood donors.

PMID- 11520418
TI  - Safety of Italian plasma for fractionation with respect to contamination with
      human herpes virus 8.

PMID- 11520419
TI  - GB virus C infection in blood donors from Cordoba, Argentina.

PMID- 11520420
TI  - Streptomycin-dependent panagglutinin causing error in forward blood grouping.

PMID- 11520421
TI  - Universal leucocyte-depletion of blood components: cell concentrates and plasma.

PMID- 11520422
TI  - A critical assessment of some biomarker approaches linked with dietary intake.
AB  - In this review many examples are given of the complexities involved in using some
      biomarkers in relation to assessing the effects of dietary exposure, when there
      is frequently a need to determine changes following long-term low level exposure
      to dietary components. These range from understanding why the biomarker might be
      valuable and how best it can be measured, to the pitfalls which can occur in the
      interpretation of data. Analytical technique is considered in relation to folate
      and selenium, and flavonoid and carotenoid species are used to illustrate how the
      metabolism of a compound may alter the validity or adequacy of a marker. Vitamin
      A is discussed in relation to the difficulties which can arise when there are
      several biomarkers that may be available to assess exposure to one nutrient.
      Vitamin B12 is discussed in relation to the dietary choices made by individuals.
      Possible interactions and the role of measuring total antioxidant capacity is
      considered in some detail. In contrast to most nutrients, there is a marked lack
      of biomarkers of either exposure or effect for most non-nutrients. The role of
      biological effect monitoring is considered for dietary contaminants, fumonisins
      and polyhalogenated aromatic hydrocarbons. Aflatoxins are discussed to exemplify
      food contaminants for which the biomarker approach has been extensively studied.
      Finally some compounds which are deliberately added to foods and some which
      appear as processing contaminants are each considered briefly in relation to the
      requirement for a biomarker of exposure to be developed.

PMID- 11520424
TI  - Biomarkers in disease and health.
AB  - Biomarkers have considerable potential in aiding the understanding of the
      relationship between diet and disease or health. However, to assess the role,
      relevance and importance of biomarkers on a case by case basis it is essential to
      understand and prioritise the principal diet and health issues. In the majority
      of cases, dietary compounds are only weakly biologically active in the short
      term, have multiple targets and can be both beneficial and deleterious. This
      poses particular problems in determining the net effect of types of foods on
      health. In principle, a biomarker should be able to contribute to this debate by
      allowing the measurement of exposure and by acting as an indicator either of a
      deleterious or of an enhanced health effect prior to the final outcome. In this
      review, the examples chosen - cancer (stomach, colon/rectal, breast); coronary
      heart disease and osteoporosis - reflect three major diet-related disease issues.
      In each case the onset of the disease has a genetic determinant which may be
      exacerbated or delayed by diet. Perhaps the most important factor is that in each
      case the disease, once manifest, is difficult to influence in a positive way by
      diet alone. This then suggests that the emphasis for biomarker studies should
      focus on predictive biomarkers which can be used to help in the development of
      dietary strategies which will minimise the risk and be of greater benefit.

PMID- 11520423
TI  - A critical evaluation of the application of biomarkers in epidemiological studies
      on diet and health.
AB  - One of the problems which may beset epidemiological studies is the difficulty of
      accurately measuring the dietary intakes of participants. Biomarkers of diet
      promise to provide a more accurate measure of dietary intake and a more objective
      one in that they are not reliant on the subject's memory. This review considers
      some issues of importance in epidemiology when information is obtained from
      biomarkers. The approach taken is to use examples both of normal dietary
      constituents and of contaminants in relation to a range of diet and health
      questions to illustrate these points. A brief overview of the role of sample
      collection, processing and storage is given including some generic
      recommendations for maximising the reliability of subsequent analytical data.
      Using the examples of phytoestrogens and iodine the question of whether
      biomarkers can accurately reflect the intake of the dietary constituents of
      interest at the population level or at the individual level is considered. The
      relationship of the biomarker to the natural history of the disease is
      exemplified using the role of folate in neural tube defects. Finally, intakes of
      vitamin D and heterocyclic amines are used to illustrate the integration of
      biomarkers into epidemiological studies of prostate and colorectal cancer,
      respectively. It is concluded that biomarkers may provide a more accurate and
      objective measure of diet than estimates of current or usual intake but that this
      approach also has limitations. A combination of methods will probably prove to be
      most valuable and this approach is being taken in current large prospective
      studies.

PMID- 11520425
TI  - Role of biomarkers in nutritional science and industry - a comment.
AB  - We are encountering a significant progress in nutritional knowledge, relevant to
      the practice of all aspects of human nutrition, medicine and public health. So,
      it is conceivable that we may view the role of nutrition differently in the
      future. The diet may not only provide an adequate amount of nutrients to meet the
      metabolic requirements, but could also contribute to improving human health
      status. As a consequence, extracts of plants or single compounds thereof which
      are believed to benefit human health need to be identified and developed for the
      food market to complement a balanced diet. The assessment of risk and benefit of
      constituents of a diet or plants will be a challenge for scientists working in
      this area. The number of compounds to be tested is enormous. Their impact on
      human health is supposed to be through prevention. Their effect on the human
      system may be modest, yet still significant when consumed over an entire
      lifespan. Trials employing traditional clinical endpoints, for many reasons,
      appear not to be feasible to investigate the relevance of these compounds on
      human health. Rather biomarkers, which are 'surrogate endpoints' for clinical
      events, may be used in the field of nutritional science. These biomarkers have to
      be highly sensitive and specific, non- or minimally invasive and inexpensive and
      they need to be validated and standardized. The biomarker concept may prove
      essential in nutritional science to demonstrate the effect of diet constituents
      on human health.

PMID- 11520426
TI  - Vitamin D status and its adequacy in healthy Danish perimenopausal women:
      relationships to dietary intake, sun exposure and serum parathyroid hormone.
AB  - We conducted this study to assess the prevalence of vitamin D insufficiency in a
      population of normal perimenopausal women, to examine the influence of sun
      exposure and vitamin D intake on the concentration of 25-hydroxyvitamin D (25OHD)
      and to examine the association between parathyroid hormone (PTH) and 25OHD. A
      total of 2016 healthy women aged 45-58, who had recently undergone a natural
      menopause, were enrolled over a 2.5-year period in the Danish Osteoporosis
      Prevention Study. A marked seasonal fluctuation of 25OHD was seen, with an abrupt
      rise in June and high values until October. The fluctuation could be related to
      number of hours of sunshine per month with a two months time lag. Dietary vitamin
      D intake, vitamin supplementation, sunlight exposure, and use of sun-bed were all
      significantly related to 25OHD concentrations. Sun exposure seemed to contribute
      the most. The overall prevalence of vitamin D deficiency (defined as serum ) was
      7 %. However, in the subgroup avoiding direct sunshine and abstaining from
      vitamin D supplementation 32.8 % were vitamin D deficient in the winter-spring
      period. Although mean PTH was increased in the group with low serum 25OHD, PTH
      was not a sensitive marker of hypovitaminosis D in the individual, as only 16 %
      of those with vitamin D deficiency had PTH levels above normal range. Thus, we
      have shown, that healthy middle-aged Danish women are prone to vitamin D
      insufficiency in the winter-spring period, if they avoid sun exposure in the
      summer period and abstain from vitamin D supplementation.

PMID- 11520427
TI  - Biomarkers for exposure to dietary flavonoids: a review of the current evidence
      for identification of quercetin glycosides in plasma.
AB  - Quercetin, a polyphenol with potential health effects, is absorbed by humans and
      measurement in plasma can be used as a biomarker for intake. However, the
      chemical nature of the quercetin in blood is still not known, although one
      possibility is that glucosides are found in an unchanged form from the original
      food. We propose that the existence of quercetin glucosides in plasma is
      unlikely, since the metabolic beta-glucosidase capacity of the small intestine
      and of the liver is too great for quercetin glucosides to escape deglycosylation.
      We critically examine the limited number of studies which purport to detect
      quercetin glycosides in blood and the current evidence for the absorption of
      these compounds from the gastrointestinal tract. We emphasise the need for
      comprehensive identification of circulating compounds, since polyphenol
      glucuronides, the expected metabolites in plasma, have almost identical
      chromatographic properties to the glucosides at acid pH. Studies on the nature of
      quercetin metabolites in plasma are urgently needed so that the proposed
      biological activities of quercetin can be re-assessed and that a suitable
      biomarker of exposure can be established.

PMID- 11520429
TI  - Brain in human nutrition and variant Creutzfeldt-Jakob disease risk (vCJD):
      detection of brain in retail liver sausages using cholesterol and neuron specific
      enolase (NSE) as markers.
AB  - No information is available about the consumption of brain via meat products.
      With respect to the new variant of Creutzfeldt-Jakob disease (vCJD) and the
      presumed food-borne transmission of bovine spongiform encephalopathy (BSE) to
      humans, a preliminary survey for brain and/or spinal cord (tissues of the central
      nervous system, CNS) was conducted. We applied a previously developed integrated
      procedure using cholesterol and neuron specific enolase (NSE) as markers.
      Quantification of cholesterol had to be backed up by NSE immunochemistry in order
      to account for low specificity and relatively high variances. Out of 126 high
      quality finely graded liver sausages, five samples (4 %) showed positive NSE
      immunoresponses. In four of these samples a transgression of the normal maximum
      cholesterol content was obtained. The identification of such a considerable
      number of CNS-positive sausages indicates that brain consumption is not as rare
      as previously assumed. Overall, the present integrated method could be
      successfully applied for the detection of CNS in heat-treated meat products. Its
      routine application in official food control would deter illegal practice and
      thus help to control transmissible spongiform encephalopathies.

PMID- 11520428
TI  - Biomonitoring the intake of garlic via urinary excretion of allyl mercapturic
      acid.
AB  - Allium vegetables (onions, leeks, chives) and in particular garlic have been
      claimed to have health-promoting potential. This study was conducted to get
      insight into the perspectives for monitoring the intake of garlic by a biomarker
      approach. Chemically, the biomarker results from exposure to gamma-glutamyl-S
      allyl-l-cysteine, which is first hydrolysed by gamma-glutamine-transpeptidase
      resulting in the formation of S-allyl-l-cysteine. The latter compound is
      subsequently N-acetylated by N-acetyltransferase into S-allyl-mercapturic acid
      (ALMA) and excreted into urine. The mercapturic acid was measured in urine using
      gaschromatography with mass spectrometry. Thus the intake of garlic was
      determined to check the compliance of garlic intake in a placebo-controlled
      intervention study. Results indicate that S-allyl-mercapturic acid could be
      detected in 15 out of 16 urine samples of garlic supplement takers, indicating
      good compliance. In addition, the intake of garlic was also monitored in a cross
      section study of vegans versus controls in Finland, in which no differences in
      garlic consumption nor in ALMA output were recorded between vegans and controls.
      These data indicate good possibilities for further studies in the field of
      biomarkers to investigate the putative chemopreventive effects of garlic and
      garlic-containing products.

PMID- 11520430
TI  - Transcription factor NF-kappaB as a potential biomarker for oxidative stress.
AB  - There is increasing interest in the involvement of transcription factors, such as
      of the transcription factor NF-kappaB (nuclear factor-kappaB), in the
      pathogenesis of various diseases. NF-kappaB is involved in the control of the
      transcription of a variety of cellular genes that regulate the inflammatory
      response by the production of cytokines, chemokines, cell adhesion molecules and
      acute phase proteins. The involvement of NF-kappaB is especially of interest as
      it is activated by oxidative stress and its activation can be modulated by
      antioxidant compounds. The activation of NF-kappaB can be determined by the
      electromobility shift assay (EMSA) with a NF-kappaB binding-site-specific probe.
      EMSA can also be used on human mononuclear cells isolated from peripheral blood,
      which could make the assay applicable for clinical trials. The critical steps of
      the EMSA are discussed, addressing some pitfalls of the assay. The procedure that
      can be used to express NF-kappaB activity in human subjects is evaluated. This
      offers the possibility to use NF-kappaB as a functional biomarker of oxidative
      stress as illustrated by several examples of in vitro and in vivo studies.

PMID- 11520432
TI  - Molecular approaches for studying ascaridoid nematodes with zoonotic potential,
      with an emphasis on Toxocara species.
AB  - Species-specific identification of ascaridoid nematodes at any developmental
      stage is a prerequisite for detailed investigation of the life cycles,
      systematics and epidemiology of this important group, and is also crucial for the
      diagnosis of associated infections. The morphological identification of some
      species and/or their larval stages can, however, present considerable difficulty.
      Recently, PCR-based methods, using genetic markers in the internal transcribed
      spacers (ITS) of ribosomal DNA, have been shown to provide reliable alternatives
      to more traditional methods for the specific identification of nematodes. This
      article provides an account of recent research on the development of PCR-based
      methods (utilizing ITS sequences) for the specific identification of ascaridoid
      nematodes of zoonotic potential, for the diagnosis of infections, and for the
      analysis of genetic variation within and among individual nematodes and their
      populations. Prospects for using these diagnostic and analytical tools to
      investigate epidemiological and population genetic questions relating to
      ascaridoid parasites are also discussed.

PMID- 11520433
TI  - The epidemiology of ocular toxocariasis.
AB  - Ocular toxocariasis damages vision and may cause blindness. It is a relatively
      'new' disease, the histological changes having been described in 1950 and the
      causative organism identified in 1956. Many aspects of the epidemiology of
      toxocariasis are unclear. It is generally accepted that the usual route of entry
      to the eye is via the blood stream. Once the eye is invaded characteristic
      changes are produced with comparative sparing of the anterior segment. Species
      differences in susceptibility can be very marked. In Mongolian gerbils 55% of
      infected animals exhibit ocular lesions. Humans are fortunate in that they are
      far less susceptible to ocular infection. While it has been established that
      ocular toxocariasis is caused by Toxocara canis, the role of T. cati in this
      condition is still unclear. It is perhaps surprising that the prevalence of such
      a disease in humans should remain in doubt. However, the wide variation in the
      few estimates of prevalence may well be a reflection of the wide variation in
      exposure as evidenced by the wide variation in seroprevalence. A further factor
      mitigating against an identification of prevalence rates is the fact that the
      condition is usually unilateral. Most surveys of blindness stipulate a vision of
      6/60 or less in the better eye and so toxocariasis cases go unrecorded. There is
      a need for surveys which identify the level of vision in both eyes.

PMID- 11520434
TI  - Animal models in ocular toxocariasis.
AB  - Ocular toxocariasis is a clearly defined disease. However, much remains to be
      learned concerning the migratory route, ocular changes, diagnosis and treatment.
      Studies in paratenic hosts have contributed to our understanding and will yield
      more information. Various experimental animals have been used, such as mice,
      rabbits, guinea pigs, primates, hamsters and gerbils. Of these, the last appear
      to be the most appropriate model due to their high susceptibility to ocular
      infection. Results obtained from different animal models are often not comparable
      due to the fact that dose and routes of inoculation are diverse. Early stages in
      the pathogenesis of ocular toxocariasis are manifested by haemorrhages in the
      anterior chamber and iris, replaced in time by accumulations of white cells.
      Ocular migration produces an early cell reaction, formed by an infiltration of
      neutrophils accompanied by vasculitis and retinal microinfarcts. Over a period of
      time, an increase of macrophages and the distribution of the infiltrates is
      observed. Later, granulomatous lesions are formed. These do not necessarily
      contain a larva and their appearance varies in different animal models. Local
      production of IgE and the presence of specific IgG have been described.

PMID- 11520435
TI  - Toxocara in the mouse: a model for parasite-altered host behaviour?
AB  - The objective of this paper is to critically evaluate the significance of
      parasite-altered host behaviour in the Toxocara mouse model particularly in the
      light of the Manipulation Hypothesis. Murine behaviours were examined in both
      outbred and inbred strains of mice infected with different doses of Toxocara
      canis ova. Behaviours investigated included activity, exploration, response to
      novelty, anxiety, learning, memory and social behaviour. Subsequent modifications
      to the behaviour of infected mice were investigated with respect to dose
      administered and larval accumulation in the brain. There was substantial
      variation in the number of larvae recovered from brains of individual mice, which
      received similar doses of Toxocara ova. Furthermore, the numbers of larvae
      recovered at different doses differed significantly between an outbred and inbred
      strain of mouse. Alterations in infected host behaviour occurred and were related
      to the number of larvae recovered from the brain. For social behaviour in outbred
      mice, a high infection in the brain reduced levels of aggressive behaviour and
      increased levels of flight and defensive behaviours. In contrast, outbred mice
      with a low infection in the brain displayed a greater level of risk behaviour in
      respect of predator odour and the light/dark box compared to control or high
      infection mice. Post-infection, outbred mice were more immobile whereas inbred
      mice showed reduced immobility and increased digging and climbing. Impaired
      learning ability was observed in outbred mice with moderate and high levels of
      infection in the brain compared to control and low infection mice. Toxocara
      infection has an impact upon a diverse range of murine behaviours with little
      evidence for a specific and hence an adaptive alteration. Many of the effects on
      murine host behaviour by Toxocara are likely to be pathological side effects of
      infection rather than as a consequence of adaptive host-manipulation. Observed
      changes in murine behaviour may be relevant to human toxocariasis.

PMID- 11520436
TI  - A comparative study of toxocariasis and allergic asthma in murine models.
AB  - Histopathology of the lung and total IgE in serum were compared in toxocariasis
      and allergic asthma murine models using BALB/c and C57BL/6 mice. Infection with
      Toxocara canis resulted in both strains of mice in marked histological changes
      and increased levels of total serum IgE. The ovalbumin (OVA)
      sensitization/challenge treatment for the induction of allergic asthma resulted
      in similar histological changes in BALB/c and, to a less extent, in C57BL/6 mice.
      Serum IgE levels of OVA-treated C57BL/6 mice were low. Histological changes
      observed included perivascular infiltration with eosinophils and mononuclear
      cells, peribronchiolitis, alveolitis and mucus production. Although these changes
      in addition to increased IgE production did occur in T. canis-infected C57BL/6
      mice they were more pronounced in BALB/c mice. Thus, BALB/c mice appear to be the
      most appropriate strain of mice to perform studies on the possible connection
      between infection with T. canis and allergic asthma.

PMID- 11520437
TI  - Treatment of Toxocara canis infections in mice with liposome-incorporated
      benzimidazole carbamates and immunomodulator glucan.
AB  - Benzimidazole carbamates (mebendazole, albendazole and fenbendazole) are the most
      commonly used anthelmintic drugs for the treatment of larval toxocariasis
      (Toxocara canis) in paratenic hosts. However, the bioavailability of these drugs
      for tissues is very low due to their extremely low solubility, resulting in the
      administration of relatively high doses over a long period. To overcome this
      problem, neutral, negatively or positively charged and stabilized liposome drug
      carriers were examined in the chronic phase of T. canis infections in mice each
      orally inoculated with 1000 eggs. Moreover, liposomized albendazole and
      fenbendazole were co-administered with liposomized immunomodulator glucan. The
      highest efficacy of both drugs, evaluated 4 weeks after treatment, was recorded
      after their subcutaneous administration (ten doses of 25 mg kg(-1)) in stabilized
      liposomes and intramuscular co-administration of liposomized glucan (two doses of
      5 mg kg(-1)). Fenbendazole was more effective in muscles (91.5%) whereas
      albendazole was more effective in the brain (92.2%). Liposomes with incorporated
      benzimidazole carbamate anthelmintics provide sustained drug-release reservoirs
      and can considerably enhance drug efficacy. Moreover, despite suppression by T.
      canis antigens, stimulation of the immune system by the immunomodulator glucan
      potentiates the effects of these antiparasitic drugs.

PMID- 11520438
TI  - Eggs of Toxocara spp. in the environment and their public health implications.
AB  - The high prevalence of Toxocara in cats, dogs and foxes results in the
      contamination of soil with infective eggs of Toxocara spp. which are found in
      soil samples from public and private places worldwide. In Poland the most
      contaminated areas were city backyards where 38-53% of soil samples were
      positive, especially in the spring. Human exposure to infection with Toxocara
      spp. was proportional to the prevalence of eggs in the samples examined but soil
      texture was not a critical factor in the degree of soil contamination. Eggs of
      Toxocara spp. placed on the ground penetrated a sand soil profile slowly. Their
      presence in the superficial layer of soils and the role of earthworms are
      instrumental in the dissemination of Toxocara eggs.

PMID- 11520440
TI  - Fecundity and egg output by Toxocara canis in the red fox, Vulpes vulpes.
AB  - The role of the red fox Vulpes vulpes in the dissemination of eggs of Toxocara
      canis into the environment is considered with reference to female worm fecundity
      and egg output in the faeces of infected foxes collected from four localities in
      southern England. A significant positive correlation was found between female
      worm size and the number of eggs in the uterus but there was no significant
      relationship between T. canis worm numbers and egg output in fox faeces. Reliable
      estimates of worm burdens in foxes could not, therefore, be determined from
      faecal egg counts alone. The highest mean egg output of 2145.0 epg recorded from
      adult foxes indicated that fox cubs are not necessarily the main sources of
      environmental contamination with T. canis eggs. Saturated magnesium sulphate was
      found to be a more effective flotation solution than zinc sulphate and sodium
      chloride for recovering eggs from fox faecal samples.

PMID- 11520439
TI  - Prevalence of species of Toxocara in dogs, cats and red foxes from the Poznan
      region, Poland.
AB  - The prevalence of toxocariasis was evaluated for 445 dogs, 105 cats and 92 foxes
      from the Poznan region during 1997-1998. Forty one cats were infected (39%), 140
      dogs (32%) and 15 red foxes (16%). Toxocara canis was found most frequently in
      puppies up to 3 months old (58%) and T. cati in kittens 4-6 months old (64%).
      Toxocariasis was much more prevalent amongst adult foxes (14%) than adult dogs
      (3%). In contrast to cats, female dogs and foxes were less infected than males.
      The present study suggests that cats may constitute an underestimated risk of
      transmission of Toxocara spp. to humans and the progressive synatropization of
      red foxes may also increase the sources of environmental contamination with
      Toxocara eggs.

PMID- 11520441
TI  - Contamination of soils with eggs of Toxocara in a subtropical city in Argentina.
AB  - A total of 475 soil samples were collected from five public park playgrounds, 17
      kindergarten sandpits and 124 housing estates in Resistencia, a medium-sized
      subtropical-region city in Argentina, and processed by the centrifugal flotation
      method. Eggs of Toxocara spp. were present in five (3.4%) of the 146 habitats
      surveyed and in six (1.3%) of the 475 samples examined. Twenty per cent of public
      parks, 5.9% of kindergarten sandpits and 2.4% of housing estates were
      contaminated with Toxocara eggs. Depending on the number of samples examined from
      the three types of habitat, contamination by Toxocara was 0.7% in public park
      playgrounds, 1.2% in kindergarten sandpits and 1.6% in the housing estates. High
      prevalences of Ancylostomidae eggs were also found especially in public park
      playgrounds with a value of 100%, compared with 19.4% found in housing estates
      and 11.8% in kindergarten samples. These results suggest that in Resistencia,
      human infections with Toxocara are likely to occur within the limits of housing
      estates more so than in public parks or open spaces.

PMID- 11520442
TI  - Prevalence and viability of eggs of Toxocara spp. and Toxascaris leonina in
      public parks in eastern Spain.
AB  - To demonstrate the prevalence of Toxocara spp. and Toxascaris leonina eggs in
      parks in Murcia city, eastern Spain, a total 644 soil samples were examined from
      nine parks. More than 67% of parks and 1.24% of soil samples were contaminated
      and the mean egg density per sample was eggs per 100 g of soil. Over 97% of eggs
      identified were viable. Only one sample was positive for Toxascaris leonina. The
      present findings suggest that shady conditions are important for the occurrence
      and viability of Toxocara spp. and Toxascaris leonina eggs in soil as there were
      significantly more positive samples in shaded and moist areas compared with open
      and dry habitats.

PMID- 11520443
TI  - The influence of inoculum size and time post-infection on the number and position
      of Toxocara canis larvae recovered from the brains of outbred CD1 mice.
AB  - Outbred CD1 mice were administered doses of 1000 and 3000 Toxocara canis eggs and
      postmortem took place on days 7, 42 and 120 post-infection. Mice were killed by
      cervical dislocation and brains were sagitally bisected and fixed in 10% neutral
      buffered formalin prior to histological preparation and examination. The number
      of T. canis larvae were counted per brain and per section and the number of
      larvae cited for the first time per section were also recorded. These
      observations were compared by dose administered and by day of postmortem. The
      total number of larvae per brain and per section was higher for the 3000 dose
      compared to the 1000 dose. A different pattern emerged for the number of larvae
      observed in the brain over the three postmortem days depending upon the dose
      received. For the 1000 dose larval numbers increase from day 7 to day 120 whereas
      for the 3000 dose the opposite trend occurs. Larvae were assigned to one of five
      regions in the brain - the telencephalon, diencephalon, cerebellum, medulla, pons
      and brain stem and the olfactory bulb. Larvae did not show a random distribution
      in the brain. The majority of larvae were recorded from the telencephalon and the
      cerebellum. The percentage of sections with larvae in them is higher for the 3000
      dose compared to the 1000 dose for all regions of the brain. For the majority of
      regions, the percentage of sections with larvae in them increases between day 7
      and 42 and then decreases by day 120 and this is most pronounced for the
      cerebellum. For the telencephalon and diencephalon only, more larvae were
      detected on the right hand side of the brain compared to the left hand side.
      Statistical analysis revealed that dose and brain region are significant factors
      which influence the number of larvae observed in histological sections of the
      brain but day post-infection is not.

PMID- 11520444
TI  - Helminths in the wolf, Canis lupus, from north-western Spain.
AB  - Fifteen helminth species were collected from 47 wolves (Canis lupus ) which were
      surveyed from 1993 to 1999 in northwestern Spain. These included the trematode
      Alaria alata (2.1%); the cestodes Taenia hydatigena (44.7%), T. multiceps
      (29.8%), T. serialis (2.1%), Dipylidium caninum (6.4%) and Mesocestoides sp. aff.
      litteratus (4.2%); and the nematodes Pearsonema plica (7.4%), Trichuris vulpis
      (10.6%), Trichinella britovi (12.8%), Ancylostoma caninum (8.5%), Uncinaria
      stenocephala (51.1%), Toxocara canis (6.4%) Toxascaris leonina (4.2%),
      Angiostrongylus vasorum (2.1%) and Dirofilaria immitis (2.1%). Only two wolves
      were not infected. A single infection occurred in 28.9% of the cases, but the
      commonest infracommunity (31.1%) involved three species. The helminths Alaria
      alata, Taenia hydatigena, Mesocestoides sp. aff. litteratus, P. plica, Trichuris
      vulpis, and Ancylostoma caninum parasitizing C. lupus are reported for the first
      time in Spain. Taenia serialis and D. immitis are reported for the first time in
      wolves in Europe. Angiostrongylus vasorum represents a new host record for
      wolves. The helminth fauna of Spanish wolves is compared with that of other
      European wolf populations. Some epidemiological considerations of the helminth
      fauna of wolves in Spain and the health risk to humans are also discussed.

PMID- 11520446
TI  - Observations on the biology of Rhabdochona kidderi texensis, a parasite of North
      American cichlids.
AB  - An examination of a sample of benthic invertebrates collected from the Upper San
      Marcos River in southwestern Texas, USA in September 1999 revealed that the nymph
      of the ephemeropteran Tricorythodes curvatus served as natural intermediate host
      of the nematode Rhabdochona kidderi texensis (Nematoda: Rhabdochonidae), an
      intestinal parasite mainly of the Rio Grande perch (Cichlasoma cyanoguttatum) in
      this locality; the prevalence of the parasite's third- and fourth-stage larvae in
      mayflies was 6.8% with the intensity of 1-2 larvae per nymph. Live R. kidderi
      texensis eggs collected from nematodes recovered from C. cyanoguttatum in Texas
      were transported to the Czech Republic, where they were used to experimentally
      infect nymphs of the palaearctic mayfly species Paraleptophlebia submarginata;
      the development of infective third- and fourth-stage larvae in this experimental
      intermediate host was completed after approximately 10 days at 19 degrees C.
      Infected nymphs were fed to aquarium-reared fishes, four Cichlasoma
      nigrofasciatum and one Oreochromis niloticus, of which only three of the former
      became infected. The last (fourth) moult of a male nematode was observed in C.
      nigrofasciatum 23 days p.i. and adult males and gravid females with not fully
      mature (non-embryonated) eggs in uteri on days 40 and 51 p.i. The prepatent
      period of R. kidderi texensis is approximately two months.

PMID- 11520445
TI  - Mitochondrial DNA polymorphism of a triploid form of Fasciola in Japan.
AB  - Mitochondrial DNA polymorphism was characterized in a triploid form of Fasciola
      found in Japan in comparison with F. hepatica, F. gigantica and Korean Fasciola
      worm. Seventy worms of Fasciola from Japan, three of F. hepatica from Uruguay and
      Australia, two of F. gigantica from Thailand and one of Fasciola from Korea were
      used in the study. Mitochondrial DNA polymorphism was detected by restriction
      fragment length polymorphism (RFLP) using eight restriction enzymes, BamH I, Bgl
      II, Dra I, EcoR I, EcoR V, Hind III, Mfl I and Sca I. Three different types
      (types 1, 2 and 3) were detected from 76 Fasciola worms used in the study. Eight
      of 70 Japanese worms were categorized in type 2 (F. gigantica type), and the
      remaining 62 were in type 3 (F. hepatica type).

PMID- 11520447
TI  - MCP-1 and MIP-2 levels during Echinococcus granulosus infections in mice.
AB  - Ten BALB/c mice were infected with the cestode Echinococcus granulosus. After the
      infection, serum was collected at different periods of time and monocyte
      chemotactic protein-1 (MCP-1) and macrophage inflammatory protein-2 (MIP-2) were
      determined. The level of MCP-1 increased from at day 20 post infection (p.i.), to
      a maximum of on day 60 p.i., then decreased to on day 130 p.i. A second peak was
      observed at day 150 p.i. In addition, MIP-2 was detectable in serum as late as
      day 100 p.i. The highest level was observed on day 130 p.i., and decreased
      thereafter. Serum from noninfected animals (controls) contained no detectable
      levels of either MCP-1 or MIP-2. However, MCP-1 and MIP-2 appear to be implicated
      in E. granulosus infections, but their exact role during the disease is under
      determination.

PMID- 11520448
TI  - Management of atrial flutter.
AB  - Atrial flutter is a macroreentrant arrhythmia that is associated with
      cardiovascular and pulmonary disease. In the United States, 200,000 new cases of
      atrial flutter can be expected to develop every year with a male to female ratio
      of over 2:1. This arrhythmia is associated with atrial fibrillation in over half
      the cases. It is also associated with an increased risk of thromboembolic
      complications, but less than that is seen with atrial fibrillation. The most
      common form of atrial flutter involves a large reentrant circuit within the right
      atrium, encircling the tricuspid annulus. Other, less common forms of atrial
      flutter may involve other anatomic barriers, atriotomy scars, and infarcted areas
      of the atria. Treatment of atrial flutter often involves electrical cardioversion
      and/or antiarrhythmic medications. Type I and Type III antiarrhythmic drugs are
      often used to terminate or prevent recurrent episodes and Type II (beta-blockers)
      and Type IV (calcium channel blockers) can be used to control the ventricular
      rate during atrial flutter. However, antiarrhythmic drugs alone control atrial
      flutter in only 50% to 60% of patients. Since the early 1990s, radiofrequency
      catheter ablation has been used to interrupt the reentrant circuit and prevent
      recurrences of atrial flutter. Radiofrequency ablation is acutely successful in
      over 90% of cases and avoids the long-term toxicity seen with antiarrhythmic
      drugs. Advanced mapping techniques and newer methods of delivering the
      radiofrequency lesions are being used to delineate unusual forms of atrial
      flutter and to minimize fluoroscopic exposure during the procedure.

PMID- 11520449
TI  - Arrhythmogenic right ventricular cardiomyopathy: current diagnostic and
      management strategies.
AB  - Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heart muscle disease
      of unknown etiology characterized by the peculiar right ventricular (RV)
      involvement. Distinctive pathologic features are myocardial atrophy and fibro
      fatty replacement of the RV free wall, and clinical presentation is usually
      related to ventricular tachycardias with a left bundle branch block pattern or
      ventricular fibrillation leading to cardiac arrest, mostly in young people and
      athletes. Later in the disease evolution, progression and extension of RV muscle
      disease and left ventricular involvement may result in right or biventricular
      heart failure. The diagnosis of ARVC may be difficult because of several problems
      with specificity of ECG abnormalities, different potential etiologies of
      ventricular arrhythmias with a left bundle branch morphology, assessment of RV
      structure and function, and interpretation of endomyocardial biopsy findings.
      Therefore, standardized diagnostic criteria have been proposed by the Study Group
      on ARVC of the European Society of Cardiology. According to these guidelines, the
      diagnosis of ARVC is based on the presence of major and minor criteria
      encompassing electrocardiographic, arrhythmic, morphofunctional, histopathologic,
      and genetic factors. Since the assessment of sudden death risk in patients with
      ARVC is still not well established, there are no precise guidelines to determine
      which patients need to be treated and what is the best management approach. The
      therapeutic options include beta-blockers, antiarrhythmic drugs, catheter
      ablation, and implantable cardioverter defibrillator (ICD). The ICD is the most
      effective safeguard against arrhythmic sudden death. However, its precise role in
      changing the natural history of ARVC by preventing sudden and nonsudden death
      needs to be evaluated by a prospective study of a large series of patients. In
      patients in whom ARVC has progressed to severe RV or biventricular systolic
      dysfunction with risk of thromboembolic complications, treatment consists of
      current therapy for heart failure including anticoagulant therapy. In cases of
      refractory congestive heart failure, patients may become candidates for heart
      transplantation.

PMID- 11520451
TI  - Diagnosis and management of congenital heart disease in the adult.
AB  - Currently, there are 1 million people in the United States over the age of 20
      with congenital heart disease. These adult congenital heart patients can "slip
      through the cracks of our medical system" and many are too old to be cared for in
      most pediatric institutions by pediatric cardiologists, and, unfortunately, most
      adult cardiologists are not trained in congenital heart disease. Therefore, it is
      important to understand what the common lesions are in adult congenital heart
      disease and how they should be managed. Acyanotic congenital heart disease in the
      adult population primarily involves left-to-right shunts, such as atrial septal
      defect, ventricular septal defect, patent ductus arteriosus, and obstructive
      lesions such as aortic coarctation of the aorta. The most common form of cyanotic
      congenital heart disease in adults is tetralogy of Fallot. Other complex
      conditions seen in adults include univentricular hearts, Ebstein's anomaly of the
      tricuspid valve, and corrected transposition of the great vessels. Most patients
      with congenital heart disease will need to undergo surgery, catheterization, or
      catheterization intervention. Results are excellent in the adult population. Long
      term follow-up is needed for any adult congenital heart patient receiving care in
      institutions that are well organized and well equipped, as we learn more about
      the natural and unnatural history of these conditions.

PMID- 11520452
TI  - Endothelial function and cardiovascular prevention: role of blood lipids,
      exercise, and other risk factors.
AB  - Multifactorial risk factor modification is proven to positively influence
      morbidity and mortality from both cardiovascular disease and stroke. The vascular
      endothelium has recently been a focus of interest in cardiovascular prevention.
      Data suggest that vascular endothelial dysfunction may contribute to the
      pathophysiology of clinical ischemia, especially angina, myocardial infarction,
      and sudden death. Endothelial dysfunction includes abnormalities of vasomotor
      tone (constriction and dilation), balance between fibrinolysis and thrombosis,
      control of the inflammatory response, and growth of vascular smooth muscle.
      Cardiovascular prevention interventions have been studied extensively and there
      are considerable data supporting a beneficial effect on endothelial dysfunction.
      The interventions that are clearly effective in improving endothelial function
      are diet and lipid-lowering therapy (especially with statin drugs), use of
      angiotensin-converting enzyme inhibitors, hormone replacement therapy, vitamin E,
      and proper physical exercise. Many challenging issues remain unsolved, however,
      and the endothelium at both the molecular and cellular levels must be further
      investigated for both research and clinical interests.

PMID- 11520450
TI  - Evaluation of the Emergency Department chest pain patient.
AB  - Patients presenting to the Emergency Department with chest pain are common and
      often present diagnostic difficulties. Because of the limitations of the initial
      evaluation, the majority of patients are admitted, although many are later found
      to have noncardiac causes for their symptoms. Recognition of these limitations
      has driven the investigation of newer evaluation techniques and protocols in an
      attempt to improve diagnostic sensitivity without increasing overall costs. These
      have included modifications of the standard ECG, and use of newer myocardial
      markers such as mass assays for CK-MB and troponin T and I. Use of acute rest
      myocardial perfusion imaging has also been shown to be a highly valuable
      technique for risk stratification of the intermediate- to low-risk chest pain
      patient.

PMID- 11520453
TI  - Robotic heart surgery.
AB  - Advances in computer and robotic technology are transforming cardiac surgery,
      overcoming the limitations of conventional endoscopic tools. Using minimal access
      through 5 millimeter ports, computer-enhanced instruments provide superhuman
      dexterity through tremor filtration and motion scaling, and are capable of
      precise manipulation in confined body cavities. Using these technologies,
      endoscopic beating heart coronary bypass surgery as well as complex mitral valve
      repairs have been performed in the last few years. However, the current world
      experience with robotic heart surgery is mostly anecdotal, retrospective, and
      noncontrolled. Results of rigorous prospective randomized studies in the United
      States under Food and Drug Administration approved protocols, are awaited. The
      use of robotic telemanipulation technology for heart surgery is restricted in the
      United States to patients enrolled in clinical studies in a few elite centers.
      Further refinement in robotic and image-guided technology for cardiac surgery may
      further expand the use of computer enhanced instrumentation in the near future.

PMID- 11520454
TI  - The AIDS disease of CD4C/HIV transgenic mice shows impaired germinal centers and
      autoantibodies and develops in the absence of IFN-gamma and IL-6.
AB  - The mechanisms responsible for degeneration of germinal centers (GC) and
      follicular dendritic cell (FDC) networks during progression to AIDS remain
      elusive. Here, we show that CD4(+) T cells from CD4C/HIV-1 Tg mice, which develop
      a severe AIDS-like disease, express low levels of CD40 ligand. Accordingly, GC
      formation, FDC networks, and immunoglobulin isotype switching are impaired in
      these animals. However, Tg B cells respond to in vitro CD40 stimulation. Total
      serum IgG levels are reduced in Tg mice, whereas total IgM levels are increased
      with a significant amount showing DNA specificity. IFN-gamma- and IL-6-deficient
      CD4C/HIV Tg mice also develop the AIDS-like disease and produce auto-Ab. Thus,
      CD4C/HIV Tg mice have immune dysfunction accompanied by autoimmune responses.

PMID- 11520455
TI  - Localization of the 3' IgH locus elements that effect long-distance regulation of
      class switch recombination.
AB  - Four transcriptional enhancers lie downstream of the immunoglobulin heavy chain
      locus: Calpha3'/hs3a, hs1,2, hs3b, and hs4. Although individually weak, these
      elements have strong transcriptional synergies when combined and they altogether
      behave as a locus control region. Previous knockout experiments in the 3' region
      have shown that both hs3a and hs1,2 are dispensable for normal expression and
      rearrangement of the IgH locus but that their replacement with a transcribed neo
      gene severely affects class switch recombination. Here we show that even in the
      absence of a neo gene, joint deletion of the last two 3' enhancers, hs3b and hs4,
      severely impairs germline transcription and class switching to most isotypes and
      may in addition affect mu gene expression in resting B cells.

PMID- 11520456
TI  - Molecular competition for NKG2D: H60 and RAE1 compete unequally for NKG2D with
      dominance of H60.
AB  - NKG2D is a potent activating receptor on natural killer cells, T cells, and
      macrophages. Mouse NKG2D interacts with two cell surface ligands related to class
      I MHC molecules: RAE1 and H60. We used soluble versions of NKG2D, RAE1, and H60
      to characterize their interactions. RAE1 and H60 each bind NKG2D with nanomolar
      affinities, indicating tighter binding than most cell surface immune
      interactions, but NKG2D binds to H60 with approximately 25-fold higher affinity
      than to RAE1. RAE1 and H60 compete directly for occupancy of NKG2D, and, thus,
      NKG2D can be occupied by only one ligand at a time. The NKG2D-H60 interaction is
      more temperature dependent and makes greater use of electrostatic interactions
      than the NKG2D-RAE1 interaction. The distinct thermodynamic profiles provide
      insights into the different molecular mechanisms of the binding interactions.

PMID- 11520457
TI  - The truncated cytoplasmic tail of HLA-G serves a quality-control function in post
      ER compartments.
AB  - In contrast to the current model of MHC class I trafficking, which predicts that
      once a MHC class I molecule leaves the ER, it moves to the cell surface by bulk
      flow, we show that HLA-G that is loaded with suboptimal peptides is retrieved
      from post-ER compartments to the ER. Loading of HLA-G with high-affinity peptides
      abrogates this retrieval due to the lack of binding affinity to coatomer.
      Moreover, the loss of the endocytosis motif in the truncated cytoplasmic tail
      results in the prolonged half-life of HLA-G on the cell surface. Our findings
      reveal that surface expression of HLA-G can be further regulated in post-ER
      compartments and that the truncated cytoplasmic tail plays a critical role in
      such quality-control mechanisms.

PMID- 11520458
TI  - Subversion of the T/B lineage decision in the thymus by lunatic fringe-mediated
      inhibition of Notch-1.
AB  - Notch-1 signaling is essential for lymphoid progenitors to undergo T cell
      commitment, but the mechanism has not been defined. Here we show that thymocytes
      ectopically expressing Lunatic Fringe, a modifier of Notch-1 signaling, induce
      lymphoid progenitors to develop into B cells in the thymus. This cell fate switch
      resulted from Lunatic Fringe-mediated inhibition of Notch-1 function, as revealed
      by experiments utilizing lymphoid progenitors in which Notch-1 activity was
      genetically manipulated. These data identify Lunatic Fringe as a potent regulator
      of Notch-1 during the T/B lineage decision and show that an important function of
      Notch-1 in T cell commitment is to suppress B cell development in the thymus.

PMID- 11520459
TI  - Sulfation of L-selectin ligands by an HEV-restricted sulfotransferase regulates
      lymphocyte homing to lymph nodes.
AB  - Lymphocytes home to lymph nodes, using L-selectin to bind specific ligands on
      high endothelial venules (HEV). In vitro studies implicate GlcNAc-6-sulfate as an
      essential posttranslational modification for ligand activity. Here, we show that
      genetic deletion of HEC-GlcNAc6ST, a sulfotransferase that is highly restricted
      to HEV, results in the loss of the binding of recombinant L-selectin to the
      luminal aspect of HEV, elimination of lymphocyte binding in vitro, and markedly
      reduced in vivo homing. Reactivity with MECA 79, an adhesion-blocking mAb that
      stains HEV in lymph nodes and vessels in chronic inflammatory sites, is also lost
      from the luminal aspects of HEV. These results establish a critical role for HEC
      GlcNAc6ST in lymphocyte trafficking and suggest it as an important therapeutic
      target.

PMID- 11520460
TI  - Wasp recruitment to the T cell:APC contact site occurs independently of Cdc42
      activation.
AB  - Cdc42 and WASP are critical regulators of actin polymerization whose function
      during T cell signaling is poorly understood. Using a novel reagent that
      specifically detects Cdc42-GTP in fixed cells, we found that activated Cdc42
      localizes to the T cell:APC contact site in an antigen-dependent manner. TCR
      signaling alone was sufficient to induce localization of Cdc42-GTP, and
      functional Lck and Zap-70 kinases were required. WASP also localized to the T
      cell:APC contact site in an antigen-dependent manner. Surprisingly, WASP
      localization was independent of the Cdc42 binding domain but required the proline
      rich domain. Our results indicate that localized WASP activation requires the
      integration of multiple signals: WASP is recruited via interaction with SH3
      domain-containing proteins and is activated by Cdc42-GTP concentrated at the same
      site.

PMID- 11520461
TI  - Stat3 in thymic epithelial cells is essential for postnatal maintenance of thymic
      architecture and thymocyte survival.
AB  - This study describes abnormalities of the thymus in mice in which the Stat3 gene
      has been specifically disrupted behind the keratin 5 promoter. In these mice,
      virtually all of the thymic epithelial cells (TEC) were deficient for Stat3
      activation. Adult mutant mice developed severe thymic hypoplasia, which included
      alterations in the cortical TEC architecture that coincided with the loss of
      thymocytes. Even during the asymptomatic period of preadolescence, these mice
      exhibited a higher susceptibility of the thymus to suboptimal doses of
      dexamethasone or gamma-irradiation, while their thymocytes per se were no more
      sensitive than controls. These results indicate that Stat3 in TEC plays an
      essential role in maintaining thymic architecture and thymocyte survival.

PMID- 11520462
TI  - Regulation of Th2 cell differentiation by mel-18, a mammalian polycomb group
      gene.
AB  - Polycomb group (PcG) gene products regulate homeobox gene expression in
      Drosophila and vertebrates and also cell cycle progression of immature
      lymphocytes. In a gene-disrupted mouse for polycomb group gene mel-18, mature
      peripheral T cells exhibited normal anti-TCR-induced proliferation; however, the
      production of Th2 cytokines (IL-4, IL-5, and IL-13) was significantly reduced,
      whereas production of IFNgamma was modestly enhanced. Th2 cell differentiation
      was impaired, and the defect was associated with decreased levels in
      demethylation of the IL-4 gene. Significantly, reduced GATA3 induction was
      demonstrated. In vivo antigen-induced IgG1 production and Nippostrongylus
      brasiliensis-induced eosinophilia were significantly affected, reflecting the
      deficit in Th2 cell differentiation. Thus, the PcG gene products play a critical
      role in the control of Th2 cell differentiation and Th2-dependent immune
      responses.

PMID- 11520463
TI  - TACI-Ig neutralizes molecules critical for B cell development and autoimmune
      disease. impaired B cell maturation in mice lacking BLyS.
AB  - BLyS and APRIL have similar but distinct biological roles, mediated through two
      known TNF receptor family members, TACI and BCMA. We show that mice treated with
      TACI-Ig and TACI-Ig transgenic mice have fewer transitional T2 and mature B cells
      and reduced levels of circulating immunoglobulin. TACI-Ig treatment inhibits both
      the production of collagen-specific Abs and the progression of disease in a mouse
      model of rheumatoid arthritis. In BLyS-deficient mice, B cell development is
      blocked at the transitional T1 stage such that virtually no mature B cells are
      present, while B-1 cell numbers are relatively normal. These findings further
      elucidate the roles of BLyS and APRIL in modulating B cell development and
      suggest that BLyS is required for the development of most but not all mature B
      cell populations found in the periphery.

PMID- 11520464
TI  - Analysis of type 2 immunity in vivo with a bicistronic IL-4 reporter.
AB  - Effector T cells mediate adaptive immunity and immunopathology, but methods for
      tracking such cells in vivo are limited. We engineered knockin mice expressing IL
      4 linked via a viral IRES element with enhanced green fluorescent protein (EGFP).
      Reporter T cells primed under Th2 conditions showed sensitive and faithful EGFP
      expression and maintained endogenous IL-4. After Nippostrongylus infection,
      reporter expression demonstrated the evolution of type 2 immunity from tissue
      lymphocytes and thence to lymph node CD4(+) T cells, which subsequently migrated
      into tissue. The appearance of EGFP(+) CD4(+) T cells in tissue, but not in lymph
      nodes, was Stat6-dependent. Transferred EGFP(+) CD4(+) T cells from infected
      animals conferred protection against Nippostrongylus to immunodeficient mice.
      These mice will provide a valuable reagent for assessing immunity in vivo.

PMID- 11520465
TI  - Role of Janus kinase 3 in mast cell-mediated innate immunity against gram
      negative bacteria.
AB  - Mast cells play a pivotal role in innate host immune response to gram-negative
      bacteria. We report that Janus kinase 3 plays a role in mast cell-mediated
      bacterial clearance and neutrophil recruitment by regulating the release of tumor
      necrosis factor from mast cells. The role of JAK3 in mast cell-facilitated
      neutrophil recruitment and bacterial clearance was investigated by comparing the
      neutrophil influxes and bacterial clearance in mast cell-deficient W/W(v) mice
      reconstituted with JAK3(+/+) or JAK(-/-) mast cells. The neutrophil influx,
      bacterial clearance, and survival outcome in W/W(v) mice reconstituted with
      JAK3(+/+) mast cells was better than in W/W(v) mice reconstituted with JAK3(-/-)
      mast cells. These findings provide evidence that JAK3 is a key regulator of mast
      cell-mediated innate immunity against gram-negative bacteria.

PMID- 11520466
TI  - The earliest stages of B cell development require a chemokine stromal cell
      derived factor/pre-B cell growth-stimulating factor.
AB  - Environmental factors essential for the first stages of B lymphopoiesis remain
      elusive. Here, we report that immediately after commitment to B lineage,
      precursors become dependent on a chemokine SDF-1 and its receptor CXCR4 using
      mutant and radiation chimeric mice. In bone marrow, generation of the earliest
      identifiable B cell precursor populations requires CXCR4. In fetal liver, we
      identified Lin(-)CD19(-)c-kit(+)IL-7Ralpha(+)AA4.1(+), the earliest unipotent B
      cell precursor population, and found that its development was severely affected
      in SDF-1(-/-) embryos but not in IL-7(-/-) embryos. Lin(-) T cell progenitors
      appeared normal in SDF-1(-/-) embryos. Moreover, SDF-1 exhibited specific
      biologic activities on the earliest B cell precursors. SDF-1 provides the first
      example of a cytokine responsible for the earliest B lineage stages.

PMID- 11520468
TI  - Interest and limitations of projective techniques in the assessment of
      personality disorders.
AB  - Assessing personality disorders (PD) remains a difficult task because of
      persistent problems linked to concurrent validity of existing instruments, which
      are all structured interviews or self-report inventories. It has been advocated
      that indirect methods, projective techniques in particular, can strengthen PD
      assessment methods. The thematic apperception test (TAT) may be a significant
      adjuvant method of PD assessment.

PMID- 11520467
TI  - Personality abnormality in severe mental illness and its influence on outcome of
      intensive and standard case management: a randomised controlled trial.
AB  - One hundred fifty-five (77%) of 201 participants recruited in a trial of
      intensive vs standard case management of patients with recurrent psychotic
      illness had their personality status measured before treatment and were followed
      up for two years. The primary outcome was the total number of days spent in
      psychiatric hospitalisation in the two years following randomisation. Thirty
      three (21%) of the patients had a personality disorder and their duration of
      hospital stay (105 days) was greater than in those without personality disorder
      (56 days). There was weak evidence that intensive case management more effective
      in reducing the duration of care in those with personality disorder than in those
      without personality disorder.

PMID- 11520469
TI  - Envy manifestations and personality disorders.
AB  - Personality disorders are frequently associated with socially unacceptable
      behaviours that might not be always considered deviant. On the other hand, envy
      has been linked with various forms of maladjustment such as interpersonal
      conflicts, low self-esteem, depression, anxiety, aggressiveness, and even
      criminal behaviour such as vandalism and even murder. According to the DSM-IV,
      none of the personality disorders, except the narcissistic personality, is
      formally associated with envy. Nevertheless, this "deadly sin" is so omnipresent
      in human relationships that it cannot be restricted only to the narcissistic
      personalities. Most scholars recognise that people would deny that they envy
      someone else since envy is socially considered as highly undesirable; verbal
      reports are expected to be biased. To circumvent this difficulty, a projective
      questionnaire is proposed. We constructed two questionnaires: a direct version
      (DV) and an indirect version (IV). The sample consisted of 786 students from high
      school and university. Results suggest that the indirect version provides a more
      accurate assessment of envy.

PMID- 11520470
TI  - The expression of cognitive vulnerabilities for depression in daily life: a
      French-American study.
AB  - This prospective study provided a direct comparison of French and American
      samples concerning a cognitive diathesis for depression. Using the Experience
      Sampling Method and identical measures across sites, subjects were signaled five
      times daily by electronic devices to provide in vivo reports of negative events,
      attributions, and depressed moods. After controlling for effects associating
      clinical and demographic variables, and despite differences attributable to
      national origin, attributional style emerged as a highly significant predictor of
      the numerous specific attributions made to negative events within the course of
      daily life. However, consistent with the cognitive mediation hypothesis,
      attributional style did not directly explain depression levels. The results are
      discussed in terms of the predictive power of cognitive and personality
      assessments in understanding the day-to-day experience of depression.

PMID- 11520471
TI  - Problems in developing an instrument for the rapid assessment of personality
      status.
AB  - PURPOSE: To assess the validity of a quick assessment instrument (10 minutes) for
      assessing personality status, the Rapid Personality Assessment Schedule (PAS-R).
      SUBJECTS AND METHODS: The PAS-R was evaluated in psychotic patients recruited in
      one of the centres involved in a multicentre randomised controlled trial of
      intensive vs standard case management (the UK700 case management trial). Patients
      were assessed using both a full version of the PAS (PAS-I - ICD version) and the
      PAS-R. The weighted kappa statistic was used to gauge the (criterion-related)
      validity of the PAS-R using the PAS-I as the gold standard. Both measure code
      personality status using a four-point rating of severity in addition to recording
      individual categories of personality disorder. RESULTS: One hundred fifty-five
      (77%) of 201 patients recruited were assessed with both instruments. The weighted
      kappa statistic was 0.31, suggesting only moderate agreement between the PAS-I
      and PAS-R instruments under the four-point rating format, and 0.39 for the
      dichotomous personality disorder/no disorder separation. The sensitivity (64%)
      and specificity (82%) of the PAS-R in predicting PAS-I personality disorder were
      as satisfactory as for other screening instruments but still somewhat
      disappointing, and the PAS-R had an overall diagnostic accuracy of 78%.
      CONCLUSION: The PAS-R is a quick and rough method of detecting personality
      abnormality but is not a substitute for a fuller assessment.

PMID- 11520473
TI  - Tiapride in gerontopsychiatry.

PMID- 11520474
TI  - Addition of a frequency-weighted score to the Behavioral Pathology in Alzheimer's
      Disease Rating Scale: the BEHAVE-AD-FW: methodology and reliability.
AB  - The Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD) is a
      well-established instrument, designed to assess potentially remediable behavioral
      symptoms in Alzheimer's disease (AD) patients as well as to evaluate treatment
      outcome. It consists of 25 symptoms grouped into seven categories. Each symptom
      is scored on the basis of severity on a four-point scale. A knowledgeable
      caregiver is queried and items are scored on the basis of symptoms noted in the
      preceding two weeks. Reliability, construct validity and criterion validity data
      for the BEHAVE-AD have previously been published. Because of the significance of
      psychopathology in dementia, it is necessary to optimally describe and define the
      nature, magnitude and prevalence of behavioral symptomatology. Accordingly, a
      frequency component was added to each of the 25 items of the BEHAVE-AD scale. The
      objective of the present report is to describe this new Behavioral Pathology in
      Alzheimer's Disease Frequency-Weighted Severity Scale (BEHAVE-AD-FW) and to
      establish its inter-rater reliability. In this investigation the BEHAVE-AD-FW
      scale was administered to caregivers of 28 patients with either mildly impaired
      cognitive function or a dementia diagnosis. Two clinicians separately and
      independently rated the responses. Analyses determined that the intraclass
      correlation coefficients (ICCs) for the frequency component varied between 0.86
      and 0.97 for each of the seven BEHAVE-AD categories (p(s) < 0.001). ICCs for the
      frequency-weighted scores (item severity score x item frequency score) ranged
      from 0.69 to 0.98 for the seven symptom categories (p(s) < 0.001). For the BEHAVE
      AD-FW total scores, the ICC was 0.91 (P < 0.001). These results indicate that the
      frequency-weighted component is a reliable addition to the BEHAVE-AD scale.

PMID- 11520475
TI  - Treatment of the agitation of late-life psychosis and Alzheimer's disease.
AB  - In older as well as younger people, antipsychotic medication is commonly used to
      treat psychoses. In clinical practice, antipsychotic medication is also used to
      control severe behavioral disturbances such as agitation, wandering, self
      mutilation, as well as assaultiveness. Neuroleptic and non-neuroleptic drug
      treatments are used to control severe agitation and disruptive behavior. Among
      typical neuroleptics, very low doses (e.g., 0.25 mg of haloperidol 1-4 times per
      day) may be effective and limit the development of severe extrapyramidal
      reactions. Recent experience suggests that the atypical neuroleptics, olanzaine,
      risperidone, and quetiapine, are also useful for controlling severe agitation in
      elderly demented nursing home residents. The benzamides are also known for the
      treatment of behavioral disturbances in Europe, but there is little experience in
      the U.S.A. Although research studies in this area are virtually nonexistent,
      growing clinical experience suggests that the following may be quite useful: 1)
      trazodone; 2) buspirone (Buspar); 3) anticonvulsants (e.g., valproate); and 4)
      beta-blockers.

PMID- 11520476
TI  - The preclinical pharmacologic profile of tiapride.
AB  - Tiapride is a benzamide derivative that has been used successfully in the clinic
      for a number of years for the treatment of agitation and aggressiveness in
      elderly patients. Like many substituted benzamides, tiapride specifically blocks
      dopamine receptors in the brain. It has affinity for dopamine D(2) (IC(50) = 110
      320 nM) and D(3) (IC(50) = 180 nM) receptors in vitro but lacks affinity for
      dopamine D(1) and D(4) receptors and for non-dopaminergic receptors including
      H(1), alpha(1), alpha(2)-adrenergic and serotonergic receptors. Tiapride also
      shows dose-related inhibition of [3H]-raclopride binding in limbic areas and in
      the striatum of the rat in vivo (ED(50) approximately 20 mg/kg, ip). In
      microdialysis experiments, tiapride (over the range 10-30 mg/kg, ip) increased
      extracellular levels of dopamine in the nucleus accumbens and striatum, a
      reflection of its blockade of postsynaptic dopamine receptors in these brain
      areas. In behavioral experiments in rats, lower doses of tiapride (ED(50) = 10
      mg/kg, ip) antagonised dopamine agonist-induced hyperactivity while higher doses
      (ED(50) = 60 mg/kg, ip) were required to block stereotyped movements. In
      addition, doses of tiapride up to 200 mg/kg, ip failed to induce catalepsy, an
      effect observed with many other drugs which block dopamine receptors. In tests of
      conditioned behavior in rats, tiapride was found to give rise to an interoceptive
      stimulus associated with dopamine receptor blockade at doses (ED(50) = 2.2 mg/kg,
      ip) much lower than those producing motor disturbances or sedation (ED(50) = 40
      mg/kg, ip), in striking contrast to a range of conventional or atypical
      neuroleptics that produced interoceptive stimulus and sedation at similar doses.
      Furthermore, the acquisition by rats of a place-learning task in a water maze was
      not affected by tiapride (over the range 3-30 mg/kg, ip), whereas haloperidol
      (MED = 0.25 mg/kg, ip) and risperidone (MED = 0.03 mg/kg, ip) impaired
      performance. The preclinical pharmacologic and behavioral profile of tiapride
      suggests that its clinical activity may be due to a selective blockade of
      dopamine D(2) and D(3) receptors in limbic brain regions. The results are also
      consistent with a lack of motor or cognitive side effects.

PMID- 11520477
TI  - Comparative effects of pharmacotherapy on the maintenance of cognitive function.
AB  - The quality of human cognitive performance appears today as one of the main
      components of quality of life, whatever the age. Ageing by itself and most of the
      diseases affecting the central nervous system alter higher brain functions such
      as memory, vigilance and attention. Dementia is the most acute example, with a
      cascade of behavioral and psychological consequences (BPSD), which are the main
      cause of the caregiver's burden and need specific pharmacotherapy. In this
      respect, the problem will be the choice of the best drug in situations such as
      wandering, agitation, violence, and screaming. The psychotropics, however, should
      not deteriorate the already disturbed cognition of the patients. This is the
      reason why we propose to establish for each drug, and notably for the
      antipsychotics, a precise and exact "cognitive mapping"; in other words, to
      measure the effects of drugs on the different components of cognition. The
      results of such studies will be predictive of the future phase III clinical
      trials and therapeutic responses. As an illustration of this approach we shall
      relate two studies, TIATEM (phase I) and TIAGE (phase III/IV), leading to the
      determination of a good cognitive safety profile of an atypical neuroleptic drug,
      tiapride.

PMID- 11520478
TI  - Clinical management of agitation in the elderly with tiapride.
AB  - Agitated behaviors such as uncooperativeness with necessary care, motor
      hyperactivity, and verbal or physical aggression are some of the most commonly
      reported complications in dementia and organic disorders in elderly subjects.
      These symptoms present greater clinical challenges and management issues than the
      cognitive deficits. Antipsychotics are the most commonly used psychotropic agents
      for treating these types of symptoms. The aims of this article are to review
      clinical studies with tiapride, a substituted benzamide, and more specifically to
      present recent data coming from two double-blind, randomized studies in elderly
      subjects. The first study versus melperone was conducted in Germany, with over
      176 hospitalized demented patients, and indicated that tiapride was as effective
      and safe as melperone. More recently, a multicentre, international, double-blind,
      three-parallel group study compared a 21-day treatment of tiapride to haloperidol
      and placebo and included 306 demented elderly patients with agitation and
      aggressiveness. The results showed that tiapride and haloperidol were
      significantly effective in the treatment of agitation and aggressiveness compared
      to placebo. The tiapride safety profile was found to be better than haloperidol
      for clinical acceptability, particularly for significantly fewer extrapyramidal
      symptoms in the tiapride group.

PMID- 11520480
TI  - Going from immutable to mutable atherosclerotic plaques.
AB  - Atherosclerotic coronary disease develops over several decades and was once
      thought to be an inevitable, irreversible consequence of aging. Atherogenesis is
      an inflammatory response that occurs after injury to the endothelium. Thrombosis,
      because of either endothelial erosion or plaque disruption, precipitates acute
      coronary events. Effective lipid lowering with statins has consistently and
      significantly decreased the risk that acute ischemic events will occur. The
      beneficial effects of statins likely result not only from their lipid-lowering
      effects but also from mechanisms that influence plaque behavior. Atherosclerotic
      plaques are not immutable; rather, their structure and composition can be altered
      by therapeutic modification. Ample evidence from clinical trials supports statin
      treatment in patients with stable coronary disease. Results of recent clinical
      trials support early treatment of high-risk patients with unstable coronary
      disease; early and aggressive statin treatment resulted in fewer recurrent
      ischemic events in patients with an acute coronary syndrome. Additional studies
      are needed to confirm the benefit of early statin treatment in patients with
      unstable coronary disease and to elucidate the reasons for the occurrence of
      events in treated patients. Research is also necessary to clarify the role of
      other lipids, as well as nonlipid risk factors, in the occurrence of acute
      ischemic events.

PMID- 11520481
TI  - Are we aggressive enough in lowering cholesterol?
AB  - To date, 5 major randomized, placebo-controlled statin trials--the Scandinavian
      Simvastatin Survival Study, West of Scotland Coronary Prevention Study,
      Cholesterol and Recurrent Events trial, Long-term Intervention with Pravastatin
      in Ischaemic Disease, and Air Force/Texas Coronary Atherosclerosis Prevention
      Study--have convincingly shown that total mortality and major coronary events can
      be significantly reduced by lowering levels of low-density lipoprotein
      cholesterol (LDL-C) with statin therapy. These results were achieved in a broad
      range of patients including those with and without a history of coronary artery
      disease and with elevated or average LDL-C levels. The results also support the
      large body of epidemiologic evidence demonstrating that the lower the cholesterol
      level, the lower the cardiovascular risk. Evidence now substantially supports the
      urgency of physicians to aggressively target the lowering of LDL-C levels for the
      primary and secondary prevention of coronary disease.

PMID- 11520482
TI  - Making practical sense of clinical trial data in decreasing cardiovascular risk.
AB  - Clinical studies now affirm what epidemiologic evidence has long suggested-that a
      broad range of patients can benefit from lipid reduction, including those without
      overt coronary artery disease and only moderate lipid elevations. Together, these
      studies suggest that current goals for cholesterol reduction may not be
      sufficiently stringent to slow the epidemic of heart disease in this country and
      that aggressive lipid lowering may be just what the doctor should order.

PMID- 11520483
TI  - What are the priorities for managing cholesterol effectively?
AB  - Many studies have confirmed the risk of coronary artery disease associated with
      elevated levels of low-density lipoprotein cholesterol (LDL-C). The precise role
      of other lipids, however, is still under investigation. The relation between
      elevated levels of triglycerides and low levels of high-density lipoprotein
      cholesterol (HDL-C) is complex, and the results of clinical trials evaluating
      interventions to lower triglycerides or increase levels of HDL-C have been
      equivocal. Based on the data currently available, LDL-C remains the primary
      target for treatment. Ongoing clinical trials will help to answer the question of
      how low we should set our goals for lowering cholesterol in patients at risk.

PMID- 11520484
TI  - Developing a clinical strategy for cholesterol management in an era of unanswered
      questions.
AB  - Recent clinical trials have supported the use of cholesterol-lowering therapies
      to reduce cardiovascular events. Despite these results, a number of unanswered
      questions remain, including the appropriate intensity of lipid-lowering therapy
      and the role of high-density lipoprotein cholesterol and/or triglycerides in
      cardiovascular risk assessment and reduction. In addition, the optimal treatment
      strategies for women, the elderly, and patients with diabetes are more difficult
      to determine, as these groups have comprised a minority of subjects in prior
      trials. Studies in progress will provide guidance toward effective treatment of
      these populations, the appropriate degree of lipid-lowering therapy, and the role
      of estrogen replacement therapy in postmenopausal women. In the interim, a
      clinical strategy incorporating the lessons of recent clinical evidence is
      suggested.

PMID- 11520485
TI  - Effectiveness of statins in acute coronary syndromes.
AB  - Over the past several years, results of clinical trials of lipid lowering have
      increased our understanding of the pathophysiology of coronary atherosclerosis
      and ischemia. Evidence is accumulating that cholesterol lowering has potential
      anti-ischemic effects and may have immediate consequences that have a favorable
      impact on coronary events, possibly even acute coronary syndromes. Yet, less than
      one half of all patients hospitalized for acute coronary syndromes have their
      cardiovascular risks appropriately modified. The results of recent statin trials
      provide impetus for the implementation of aggressive risk-reduction strategies in
      patients with coronary atherosclerosis, including those with recent acute
      coronary syndromes. Prevention is now a viable therapeutic goal.

PMID- 11520486
TI  - Ongoing clinical trials of statins.
AB  - Lipid-lowering treatment with statins is effective for primary and secondary
      prevention of coronary artery disease in patients with either
      hypercholesterolemia or average cholesterol levels. Several clinical trials in
      progress will investigate the use of statins in entirely elderly or diabetic
      cohorts, and larger trials will continue to include significant numbers of these
      patients, as well as greater numbers of women. Additional clinical endpoint
      trials are assessing the potential benefits of lowering lipid levels to below
      currently recommended goals and of aggressive early statin treatment to prevent
      ischemic events in patients with stable coronary disease or acute coronary
      syndromes. These trials are expected to yield important data on the relation of
      lipid reduction to the prevention of coronary artery disease and on the potential
      for extending the use of statins.

PMID- 11520487
TI  - Developmentally regulated expression of GABA receptor rho1 and rho2 subunits, L7
      and cone-rod homeobox (CRX) genes in mouse retina.
AB  - In this study, we compared the temporal expression pattern of four retinal genes;
      rho1 and rho2 that encode subunits of GABA(c) receptors, L7 that encodes Purkinje
      cell protein and CRX that encodes the cone-rod homeobox transcription factor. A
      reverse-transcription-polymerase chain reaction (RT-PCR) strategy that generated
      a linear correlation between the amount of retinal RNA and the amount of
      amplified product was used to quantify transcripts from each gene. Results with
      this method showed that the rho1 and L7 have similar developmental patterns. Both
      exhibit basal level expression before P7. From P7 to P20, the RNA levels for both
      genes were increased about 12-fold. After P20, the RNA levels remained unchanged.
      Compared to rho1 and L7, expression of rho2 began later, since the rho2 RNA could
      not be detected until P10. At P10, the rho2 RNA level was about 10% of its level
      at P35. Expression of rho2 reached its peak at a later developmental stage
      compared to that of rho1 and L7. The different temporal patterns were confirmed
      by co-amplification of rho1, rho2, and L7 in a single PCR tube. CRX RNA was
      detected at embryonic day 15 (E15) and increased progressively, in agreement with
      a prior study using in situ hybridization. These data, combined with evidence
      that the tissue distribution of rho1 and L7 RNA in the CNS are similar, indicates
      that rho1 and L7 may share common transcriptional regulatory elements.
      Furthermore, the difference in the timing of rho subunit expression suggests that
      the subunit composition of GABA(c) receptors vary during retinal development.

PMID- 11520488
TI  - Colchicine-induced cytoskeletal collapse and apoptosis in N-18 neuroblastoma
      cultures is rapidly reversed by applied S-100beta.
AB  - Brain connections depend on a stable association between dendrites and axons
      whose cytoskeleton is stabilized by the proteins MAP-2 and tau, respectively. The
      glial protein S-100beta inhibits the phosphorylation by PKC of these two
      microtubule-associated proteins. In order to determine if exogenous S-100beta can
      directly influence the cytoskeleton of living cells, cultures of N-18 cells
      (neuroblastoma clonal cell line) are treated for 30 min in serum-free medium with
      10(-6) M colchicine. In normal media, colchicine induces a rapid retraction of
      processes, membrane blebbing, nuclear collapse, and cell death. The observed
      cellular changes, due to cytoskeletal collapse after exposure to colchicine, are
      similar and consistent with the loss of processes and cytoplasmic blebbing seen
      in cells undergoing apoptosis. The addition of 20 ng/ml of S-100beta after the
      initial 30-min exposure to colchicine prevents apoptosis, nuclear collapse and
      induces the regrowth of retracted processes. Cells were treated with the Hoechst
      Stain, a fluorescent marker that binds to nuclear material, to determine the
      occurrence of apoptosis in our cultures. In our control cultures, receiving no
      drugs, we found that 15.1% of the cells were apoptotic. When colchicine was added
      to the culture medium we found that 31.6% of the cells became apoptotic. However,
      when colchicine was followed by exposure to S-100beta we found that only 5.4% of
      the cells were apoptotic. Our results suggest that extracellular application of
      the glial protein S-100beta is sufficient to reverse colchicine-induced
      cytoskeletal collapse and prevent the resultant apoptosis of the cells. The
      increased levels of S-100beta seen after brain injury and in certain neurological
      and psychiatric disorders may be considered as beneficial for brain recovery.

PMID- 11520489
TI  - Effects of short- and long-term rat hind limb immobilization on spinal cord
      insulin-like growth factor-I and its receptor.
AB  - In this study we investigated changes in the spinal cord insulin-like growth
      factor-I peptide (IGF-I) and its receptors (IGF-IR) after hind limb
      immobilization for 5 days, 2, 4, and 8 weeks. Moreover, effects on IGF-I and
      nicotinic cholinergic receptors (nAChRs) in two types of skeletal muscle were
      also investigated. IGF-I levels were measured by radioimmunoassay (RIA) whereas
      IGF-IR and nAChRs were measured by quantitative receptor autoradiography. Spinal
      cord IGF-I levels decreased significantly after 5 days, 2 and 4 weeks of
      immobilization, whereas IGF-IR increased significantly after 4 and 8 weeks
      compared to controls. In skeletal muscles, nAChRs increased significantly after 5
      days and 2 weeks in the soleus (SOL) and tibialis anterior (TIB) muscles,
      respectively, and continued up to 8 weeks in both muscles. IGF-I concentration
      decrease significantly after 4 and 8 weeks in the SOL and TIB muscles,
      respectively. Despite the normal levels of IGF-I in both muscles at the early
      time points (5 days and 2 weeks), low levels of IGF-I were observed concurrently
      in the spinal cord ipsilateral to the immobilized limb. Our findings suggest that
      the early decrease in the IGF-I level and the late upregulation in the IGF-IR in
      the spinal cord might represent a nervous system response to disuse.

PMID- 11520490
TI  - Transneuronal tracing of neural pathways controlling abdominal musculature in the
      ferret.
AB  - Abdominal musculature participates in generating a large number of behaviors and
      protective reflexes, although each abdominal muscle is frequently activated
      differentially during particular motor responses. For example, rectus abdominis
      has been reported to play less of a role in respiration than other abdominal
      muscles, such as transversus abdominis. In the present study, the inputs to
      transversus abdominis and rectus abdominis motoneurons were determined and
      compared using the transneuronal transport of two recombinant isogenic strains of
      pseudorabies virus. After a 5-day post-inoculation period, infected presumed
      motoneurons were observed principally in cord levels T10-T15 ipsilateral to the
      injections. The injection of a monosynaptic tracer, beta-cholera toxin, into
      transversus abdominis confirmed the distribution of motoneurons innervating this
      muscle. In the brainstem, neurons transneuronally infected following injection of
      pseudorabies virus into rectus abdominis or transversus abdominis were located in
      the same regions, which included the medial medullary reticular formation, the
      medullary raphe nuclei, and nucleus retroambiguus (the expiration region of the
      caudal ventral respiratory group). Double-labeled cells providing inputs to both
      rectus and transversus motoneurons were present in both the medial medullary
      reticular formation and nucleus retroambiguus. These data show that the medial
      medullary reticular formation contains neurons influencing the activity of
      multiple abdominal muscles, and support our hypothesis that this region globally
      affects the excitability of motoneurons involved in respiration.

PMID- 11520491
TI  - Effects of radiofrequency exposure on the GABAergic system in the rat cerebellum:
      clues from semi-quantitative immunohistochemistry.
AB  - The widespread use of cellular phones raises the problem of interaction of
      electromagnetic fields with the central nervous system (CNS). In order to measure
      these effects on neurotransmitter content in the CNS, we developed a protocol of
      neurotransmitter detection based on immunohistochemistry and image analysis.
      Gamma-vinyl-GABA (GVG), an inhibitor of the GABA-transaminase was injected in
      rats to increase GABA concentration in the CNS. The cellular GABA contents were
      then revealed by immunohistochemistry and semi-quantified by image analysis
      thanks to three parameters: optical density (O.D.), staining area, and number of
      positive cells. The increase in cerebellar GABA content induced by GVG 1200 mg/kg
      was reflected in these three parameters in the molecular and the granular layers.
      Therefore, control of immunohistochemistry parameters, together with appropriate
      image analysis, allowed both the location and the detection of variations in
      cellular neurotransmitter content. This protocol was used to investigate the
      effects of exposure to 900 MHz radiofrequencies on cerebellar GABA content. Both
      pulsed emission with a specific absorption rate (SAR) of 4 W/kg and continuous
      emission with high SAR (32 W/kg) were tested. We observed a selective diminution
      of the stained processes area in the Purkinje cell layer after exposure to pulsed
      radiofrequency and, in addition, a decrease in O.D. in the three cell layers
      after exposure to continuous waves. Whether this effect is, at least partly, due
      to a local heating of the tissues is not known. Overall, it appears that high
      energetic radiofrequency exposure induces a diminution in cellular GABA content
      in the cerebellum.

PMID- 11520492
TI  - Stimulation of the subthalamic vasodilator area and fastigial nucleus
      independently protects the brain against focal ischemia.
AB  - We investigated whether stimulation of the functionally discrete subthalamic
      region, subthalamic cerebrovasodilator area (SVA), which increases cerebral blood
      flow (CBF) when excited, would, like stimulation of cerebellar fastigial nucleus
      (FN), produce central neurogenic neuroprotection. A 1-h electrical stimulation of
      SVA or FN reduced infarctions triggered by permanent occlusion of middle cerebral
      artery (MCA) by 48-55% in Sprague-Dawley rats and by 59% in Fisher rats. The
      salvaging effect of SVA stimulation, similar to FN, was long lasting and reduced
      the volume of infarctions placed 72 h or 10 days later by 58 and 26%,
      respectively, in Fisher rats. Bilateral lesioning of FN neurons by the
      microinjection of ibotenic acid 5 days before SVA stimulation did not affect SVA
      evoked neuroprotection. Bilateral lesions of SVA neurons administered 5 days
      before FN stimulation had no effect on FN-induced neuroprotection but reversed
      the stimulus-locked increase in CBF accompanying FN stimulation. This study
      demonstrates that (1) excitation of neurons and/or fibers projecting through the
      SVA reduces ischemic infarctions as substantially as excitation of FN neurons;
      (2) the effects are long-lasting and not attributable to increases in cerebral
      blood flow, changes in blood gases or brain temperature, or rat strain; (3) the
      neuroprotective effects of SVA and FN stimulation are mutually independent and
      (4) FN-evoked cerebrovasodilation is mediated by SVA neurons. The SVA and FN are
      part of a neuronal system in CNS, which is distributed and, when excited, acts to
      protect the brain from ischemic injury.

PMID- 11520493
TI  - Differential regulation of forebrain glutamic acid decarboxylase mRNA expression
      by aging and stress.
AB  - In aging brain, degeneration or functional impairment of the hippocampus has been
      connected with stress dysregulation, serving to disinhibit stress responses and
      allow for glucocorticoid hypersecretion and its attendant pathophysiology.
      Hippocampal dysfunction appears to be communicated to paraventricular
      hypothalamic corticotropin-releasing hormone neurons by way of subcortical
      GABAergic neurons. As such, hippocampal-hypothalamic relays are likely to play an
      important role in age-related stress dysfunction. To test this hypothesis,
      regulation of glutamic acid decarboxylase isoform mRNA was studied in young (3
      months), middle aged (15 months) and aged (30 months) Fischer 344/Brown Norway F1
      hybrid rats. Basal expression of glutamic acid decarboxylase (GAD) 65 mRNA was
      increased in the medial preoptic area and posteromedial bed nucleus of the stria
      terminalis (BST) in aged rats relative to both middle-aged and young groups.
      Unlike young or middle-aged animals, exposure to chronic intermittent stress
      decreased GAD65 mRNA levels in the medial preoptic area and posteromedial BST of
      aged rats. Thus, while aged rats show evidence of elevated basal GABA synthesis,
      chronic stress causes differential loss of GAD in hippocampal-PVN relays,
      consistent with reduced PVN inhibition.

PMID- 11520494
TI  - Alterations in cytochrome c oxidase activity and energy metabolites in response
      to kainic acid-induced status epilepticus.
AB  - The effects of kainic acid (KA)-induced limbic seizures have been investigated on
      cytochrome c oxidase (COx) activity, COx subunit IV mRNA abundance, ATP and
      phosphocreatine (PCr) levels in amygdala, hippocampus and frontal cortex of rat
      brain. Rats were killed either 1 h, three days or seven days after the onset of
      status epilepticus (SE) by CO2 and decapitation for the assay of COx activity and
      by head-focused microwave for the determination of ATP and PCr. Within 1 h COx
      activity and COx subunit IV mRNA increased in all brain areas tested between 120%
      and 130% of control activity, followed by a significant reduction from control,
      in amygdala and hippocampus on day three and seven, respectively. In amygdala,
      ATP and PCr levels were reduced to 44% and 49% of control 1 h after seizures. No
      significant recovery was seen on day three or seven. Pretreatment of rats with
      the spin trapping agent N-tert-butyl-alpha-phenylnitrone (PBN, 200 mg kg(-1),
      i.p.) 30 min before KA administration had no effect on SE, but protected COx
      activity and attenuated changes in energy metabolites. Pretreatment for three
      days with the endogenous antioxidant vitamin E (Vit-E, 100 mg/kg, i.p.) had an
      even greater protective effect than PBN. Both pretreatment regimens attenuated KA
      induced neurodegenerative changes, as assessed by histology and prevention of the
      decrease of COx subunit IV mRNA and COx activity in hippocampus and amygdala,
      otherwise seen following KA-treatment alone. These findings suggest a close
      relationship between SE-induced neuronal injury and deficits in energy metabolism
      due to mitochondrial dysfunction.

PMID- 11520495
TI  - An association between the estrogen-dependent hypotensive effect of ethanol and
      an elevated brainstem c-jun mRNA in female rats.
AB  - We have recently demonstrated that chronic ethanol administration lowers blood
      pressure (BP) in female rats and this effect is significantly attenuated by
      ovariectomy. The present study investigated whether ethanol hypotension is
      estrogen dependent. Further, since estrogen regulates AP-1 activity, the study
      was extended to determine whether estrogen/c-jun interaction is involved in the
      estrogen-dependent hypotensive effect of ethanol. Changes in BP and heart rate
      (HR) were evaluated in radiotelemetered pair-fed sham-operated (SO),
      ovariectomized (OVX), and OVX estradiol (E2)-treated rats receiving liquid diet
      with or without ethanol (5%, w/v) for 12 weeks. The in situ hybridization
      technique was used to measure the c-jun mRNA expression in two brainstem areas,
      the nucleus tractus solitarius (NTS) and the rostral ventrolateral medulla
      (RVLM). Ethanol feeding caused significant (P<0.05) decreases in BP in SO rats
      that started at week 1 and reached its maximum (approximately 10 mmHg) at week 6
      and remained at that level till the end of week 12. In OVX rats, ethanol had no
      effect on BP during the first 5 weeks after which a decrease of 5 mmHg was
      demonstrated and remained thereafter. Estrogen replacement (17beta-estradiol
      subcutaneous pellet, 14.2 microg/day) restored the hypotensive effect of ethanol
      to a level similar to that of SO rats both in terms of magnitude and duration.
      Densitometric analysis of the in situ hybridization autoradiograms revealed that
      OVX and E2 replacement had no effect on c-jun mRNA expression in the NTS or RVLM.
      Ethanol feeding produced a significant (twofold) increase in c-jun mRNA
      expression in the RVLM of SO rats versus no effect in the NTS. The increased
      expression of c-jun mRNA observed following ethanol treatment in the RVLM of SO
      rats was abolished in OVX rats and restored to SO levels after E2 replacement.
      These findings suggest a link between the estrogen-dependent hypotensive effect
      of chronically administered ethanol and the increased expression of c-jun mRNA in
      the brainstem of female rats.

PMID- 11520496
TI  - Preserved phosphorylation of RET receptor protein in spinal motor neurons of
      patients with amyotrophic lateral sclerosis: an immunohistochemical study by a
      phosphorylation-specific antibody at tyrosine 1062.
AB  - Ret oncoprotein is a functional receptor for the glial cell line-derived
      neurotrophic factor (GDNF) family and it is expressed in motor neurons, playing
      an important role in the motor neuron function. In this study, we examined the
      expression of the phosphorylation state of tyrosine residue 1062 (Tyr-1062) of
      Ret in the spinal cords of amyotrophic lateral sclerosis (ALS), using the
      phosphorylation state specific antibody at Tyr-1062 of Ret. The
      immunohistochemical study demonstrated that Tyr-1062 of Ret was phosphorylated to
      variable extents in the surviving motor neurons of all the ALS as well as
      controls studied. This is the first report that the phosphorylation of Tyr-1062
      occurred in neurons with nononcogenic type of Ret. The Ret-signaling pathway by
      Tyr-1062 autophosphorylation is constitutively activated via the
      phosphatidylinositol 3-kinase and/or mitogen-activated protein kinase cascade for
      motoneuron survival even in the ALS motor neurons, supporting the view that GDNF
      is a candidate for therapeutic approach to ALS.

PMID- 11520497
TI  - Maternal deprivation increases 5-HT(1A) receptor expression in the CA1 and CA3
      areas of senescent Brown Norway rats.
AB  - Maternally-deprived male Brown Norway rats were classified as non-impaired or
      impaired according to their performance in the water maze when 3 and 30-32 months
      old. Age and spatial learning ability did not affect the pattern and density of
      hippocampal 5-HT(1A)-receptor mRNA in mother-reared control rats. However,
      senescent maternally-deprived rats with impaired spatial learning ability showed
      increased expression of 5-HT(1A)-receptor mRNA in the hippocampal CA1 (14%) and
      CA3 (13%) areas but not in the dentate gyrus.

PMID- 11520499
TI  - Efficient solution of ordinary differential equations modeling electrical
      activity in cardiac cells.
AB  - The contraction of the heart is preceded and caused by a cellular electro
      chemical reaction, causing an electrical field to be generated. Performing
      realistic computer simulations of this process involves solving a set of partial
      differential equations, as well as a large number of ordinary differential
      equations (ODEs) characterizing the reactive behavior of the cardiac tissue.
      Experiments have shown that the solution of the ODEs contribute significantly to
      the total work of a simulation, and there is thus a strong need to utilize
      efficient solution methods for this part of the problem. This paper presents how
      an efficient implicit Runge-Kutta method may be adapted to solve a complicated
      cardiac cell model consisting of 31 ODEs, and how this solver may be coupled to a
      set of PDE solvers to provide complete simulations of the electrical activity.

PMID- 11520498
TI  - Differentiation of human dopamine neurons from an embryonic carcinomal stem cell
      line.
AB  - Previous studies from this laboratory have demonstrated that fibroblast growth
      factor 1 together with a number of co-activator molecules (dopamine, TPA,
      IBMX/forskolin), will induce the expression of the catecholamine biosynthetic
      enzyme tyrosine hydroxylase (TH) in 10% of human neurons (hNTs) derived from the
      NT2 cell line [10]. In the present study, we found that TH induction was
      increased to nearly 75% in hNTs when cells were permitted to age 2 weeks in
      culture prior to treatment with the differentiation cocktail. This high level of
      TH expression was sustained 7 days after removal of the differentiating agents
      from the media. Moreover, the induced TH present in these cells was enzymatically
      active, resulting in the production of low levels of dopamine (DA) and its
      metabolite DOPAC. These findings suggest that hNTs may provide an important
      tissue culture model for the study of factors regulating TH gene expression in
      human neurons. Moreover, hNTs may serve, in vivo, as a source of human DA neurons
      for use in transplantation therapies.

PMID- 11520500
TI  - Some exact solutions of a generalized Fisher equation related to the problem of
      biological invasion.
AB  - The problem of biological invasion in a model single-species community is
      considered, the spatiotemporal dynamics of the system being described by a
      modified Fisher equation. For a special case, we obtain an exact solution
      describing self-similar growth of the initially inhabited domain. By comparison
      with numerical solutions, we show that this exact solution may be applicable to
      describe an early stage of a biological invasion preceding the propagation of the
      stationary travelling wave. Also, the exact solution is applied to the problem of
      critical aggregation to derive sufficient conditions of population extinction.
      Finally, we show that the solution we obtain is in agreement with some data from
      field observations.

PMID- 11520502
TI  - On the dispersion index of a Markovian molecular clock.
AB  - The number of nucleotide substitutions accumulated in a gene or in a lineage is
      an important random variable in the study of molecular evolution. Of particular
      interest is the ratio of the variance to the mean of that random variable, often
      known as the dispersion index. Because nucleotide substitution is most commonly
      modeled by a continuous-time four-state Markov chain, this paper provides a
      systematic method of computing the dispersion indices exhibited by a continuous
      time four-state Markov chain. Using this method along with computer algebra and
      Monte Carlo simulation, this paper offers partially proven conjectures that were
      supported by thorough computer experiments. It is believed that the Tamura model,
      the equal-input model and the Takahata-Kimura model always exhibit dispersion
      indices less than 2. It is also believed that a general four-state model can be
      chosen to exhibit a dispersion index of any desired magnitude, although the
      chance of a randomly chosen such model exhibiting a dispersion index greater than
      2 is as small as about 2%. Relevance of these findings to the neutral theory is
      discussed.

PMID- 11520501
TI  - Modeling epidemics caused by respiratory syncytial virus (RSV).
AB  - Respiratory syncytial virus (RSV) is the most common cause of acute lower
      respiratory tract infection in children. In this paper we use models of RSV
      transmission to interpret the pattern of seasonal epidemics of RSV disease
      observed in different countries, and to estimate epidemic and eradication
      thresholds for RSV infection. We compare the standard SIRS model with a more
      realistic model of RSV transmission in which individuals acquire immunity
      gradually after repeated exposure to infection. The models are fitted to series
      of monthly hospital case reports of RSV disease from developed and developing
      countries. The models can explain many of the observed patterns: regular yearly
      outbreaks in some countries, and in other countries cycles of alternating larger
      and smaller annual epidemics, with shifted maxima in alternate years. Previously
      these patterns have been attributed to the transmission of different strains of
      RSV. In some countries the timing of epidemics is not consistent with increased
      social contact among school children during term time being the major driving
      mechanism. Climatic factors appear to be more important. Qualitatively different
      models gave equally good fits to the data series, but estimates of the
      transmission parameter were different by a factor of 4. Estimates of the basic
      reproduction number (R(0)) ranged from 1.2 to 2.1 with the SIRS model, and from
      5.4 to 7.1 with the model with gradual acquisition of partial immunity.

PMID- 11520504
TI  - The spatial profile of visual attention in mental curve tracing.
AB  - In a curve-tracing task, subjects have to judge whether items are located on a
      single, continuous curve. Spatially separate segments of such a curve are related
      to each other through grouping criteria, like collinearity and connectedness.
      These grouping cues need to be exploited during curve tracing, but it is still an
      open issue how grouping of contour segments is achieved by the visual system.
      Many contemporary theories of visual perception assume that grouping operations
      are carried out pre-attentively, with unlimited capacity. The present study
      examines this assumption by investigating the involvement of attention in curve
      tracing. The results show that attention is directed to contour segments that
      need to be grouped together. The distribution of attention is guided by grouping
      criteria, such as connectedness. Apparently, attention is required to group
      spatially separate contour segments into a coherent representation of a curve.

PMID- 11520503
TI  - Envelope size tuning for stereo-depth perception of small and large disparities.
AB  - Stereopsis is the sense of depth derived from binocular disparities that are
      formed between targets that are matched between the two retinal images. Binocular
      matches for sustained stereopsis are based on similarity of orientation, spatial
      frequency and contrast of the two retinal images whereas matches for transient
      stereopsis depend on these parameters to a very limited extent. In this
      investigation we have tested the possibility that transient stereopsis forms
      matches between objects of similar overall size. The tuning of sustained and
      transient stereopsis to contrast-envelope size was investigated by presenting
      narrow-band Gabor targets of unequal size to the two eyes. Bandwidth for envelope
      size tuning was estimated from the range of dichoptic size-differences over which
      stereo performance remained above chance level. An equal bandwidth of 2 octaves
      was found for the sustained and transient stereo systems when stimulated with
      parallel orientation Gabors that subtended a small disparity. Sustained-stereo
      performance with orthogonal carriers was reduced with large envelope sizes.
      Bandwidth of the transient stereo system increased to 3 octaves when tested with
      a larger disparity stimulus and it was independent of carrier orientation.
      Reducing the contrast of the larger-size Gabor improved transient-stereo
      performance from near chance (48-58%) to 85-95%. Thus the bandwidth for envelope
      size tuning is much broader than indicated with equal physical contrast stimuli.
      The observed tuning to envelope size, while broad, is tighter than that observed
      for carrier spatial-frequency [Vis. Res. 38 (1998) 3057], carrier orientation
      [Vis. Res. 39 (1999) 2717] and contrast polarity [Vis. Res. 39 (1999) 4010] of
      the stimulus. Thus it would appear that envelope size and, to a greater extent,
      temporal synchrony of the dichoptic stimuli [Perception 24 (1995) 33] are the
      primary means for selecting matched binocular inputs for transient stereopsis.

PMID- 11520505
TI  - Illuminant cues in surface color perception: tests of three candidate cues.
AB  - Many recent computational models of surface color perception presuppose
      information about illumination in scenes. The models differ primarily in the
      physical process each makes use of as a cue to the illuminant. We evaluated
      whether the human visual system makes use of any of three of the following
      candidate illuminant cues: (1) specular highlight, (2) full surface specularity
      [Lee, H. C. (1986). Method for computing the scene-illuminant chromaticity from
      specular highlights. Journal of the Optical Society of America A, 3(10), 1694
      1699; D'Zmura, M., & Lennie, P. (1986). Mechanisms of color constancy. Journal of
      the Optical Society of America A, 3(10), 1662-1672], and (3) uniform background.
      Observers viewed simulated scenes binocularly in a computer-controlled Wheatstone
      stereoscope. All simulated scenes contained a uniform background plane
      perpendicular to the observer's line of sight and a small number of specular,
      colored spheres resting on the uniform background. Scenes were rendered under
      either standard illuminant D65 or standard illuminant A. Observers adjusted the
      color of a small, simulated test patch to appear achromatic. In a series of
      experiments we perturbed the illuminant color signaled by each candidate cue and
      looked for an influence of the changed cue on achromatic settings. We found that
      the specular highlight cue had a significant influence, but that the influence
      was asymmetric: greater when the base illuminant, CIE standard Illuminant A, was
      perturbed in the direction of Illuminant D65 than vice versa. Neither the full
      surface specularity cue nor the background cue had any observable influence. The
      lack of influence of the background cue is likely due to the placement of the
      test patch in front of the background rather than, as is typical, embedded in the
      background.

PMID- 11520506
TI  - Detecting changes of spatial cone-excitation ratios in dichoptic viewing.
AB  - Spatial ratios of cone excitations produced by light reflected by different
      surfaces in a scene may provide the cue for discriminating changes in illuminant
      from changes in surface reflectances. To test whether these ratios can be
      computed across the two eyes, observers were presented with simulations on a
      computer-controlled monitor of pairs of juxtaposed or separated Munsell surfaces
      undergoing an illuminant change with a small change in cone-excitation ratios or
      a change with constant cone-excitation ratios. Surfaces were viewed either
      binocularly or dichoptically. Observers reliably discriminated the two changes in
      both viewing conditions, although less well dichoptically. Cone-excitation
      ratios, which may in principle be computed retinally, may also be computed
      cortically.

PMID- 11520507
TI  - Visual aftereffects of sequential perception: dynamic adaptation to changes in
      texture density and contrast.
AB  - Two new aftereffects are described in which the comparison of successively
      presented textures can be affected by prior exposure (adaptation) to biased
      sequences. A dynamic aftereffect of texture density can be produced using changes
      in non-Fourier texture density (using balanced-dot textures). An analogous
      dynamic aftereffect is demonstrated for texture contrast. These two effects are
      dissociated experimentally by the near absence of cross-adaptation. Evidence is
      also presented that the density effect is not one of texture motion (e.g.
      expansion/contraction of texture).

PMID- 11520508
TI  - Texture contrast aftereffects are monocular; texture density aftereffects are
      binocular.
AB  - Two experiments examined interocular transfer for simple and dynamic aftereffects
      of density and contrast. Simple aftereffects of texture contrast were shown to be
      primarily monocular. Texture density aftereffects were shown to be primarily
      binocular. Similarly, dynamic aftereffects to repeated changes in contrast were
      found to be completely monocular; those to repeated changes in density were found
      to be entirely binocular. Since contrast and density aftereffects differ in their
      sensitivity to eye-of-origin, they likely depend on different neural loci, and
      are not manifestations of the same underlying adaptation. Consistent with this
      conclusion, it is proposed that, whereas contrast normalization (and perhaps
      contrast aftereffects) may be localized to simple cells in V1, density coding and
      normalization require computations only available in complex cells and beyond.

PMID- 11520509
TI  - Afferent delays and the mislocalization of perisaccadic stimuli.
AB  - Determining the precise moment a visual stimulus appears is difficult because
      visual response latencies vary. This temporal uncertainty could cause
      localization errors to brief visual targets presented before and during eye
      movements if the oculomotor system cannot determine the position of the eye at
      the time the stimulus appeared. We investigated the effect of varying neural
      processing time on localization accuracy for perisaccadic visual targets that
      differed in luminance. Although systematic errors in localization were observed,
      the effect of luminance was surprisingly small. We explore several hypotheses
      that may explain why processing delays are not more disruptive to localization
      performance.

PMID- 11520510
TI  - Saccadic countermanding: a comparison of central and peripheral stop signals.
AB  - We compared the effectiveness of central and peripheral targets in a saccadic
      countermanding task. Stop-signal reaction times (SSRTs) do not differ
      significantly for central and peripheral stop signals. Further, when central and
      peripheral stop signals are presented together, SSRTs behave as expected of
      independent processes in parallel. A linear rise-to-threshold race model (LATER)
      with independent go and stop processes describes the behavioural data
      successfully, predicting not only the latency distribution of saccades that
      escaped inhibition, but also the probability of successful countermanding.
      Central and peripheral stop signals appear to act independently and with equal
      effectiveness.

PMID- 11520511
TI  - Interaction of visual prior constraints.
AB  - The visual system relies on two types of information to interpret a visual scene:
      the cues that can be extracted from the retinal images and prior constraints that
      are used to disambiguate the scene. Many studies have looked at how multiple
      visual cues are combined. We examined the interaction of multiple prior
      constraints. The particular constraints studied here are assumptions the observer
      makes concerning the location of the light source (for the shading cue to depth)
      and the orientation of a surface (for depth based on image contours). The
      reliability of each of the two cues was manipulated by changing the contrast of
      different parts of the stimuli. We developed a model based on elements of
      Bayesian decision theory that permitted us to track the weights applied to each
      of the prior constraints as a function of the cue reliabilities. The results
      provided evidence that prior constraints behave just like visual cues to depth:
      cues with more reliable information have higher weight attributed to their
      corresponding prior constraint.

PMID- 11520513
TI  - Evidence from a line bisection task for visuospatial neglect in left
      hemiparkinson's disease.
AB  - The perception of extrapersonal space in Parkinson's disease was examined with
      two line bisection tasks. One was a conventional pencil and paper test, the line
      bisection section of the Behavioural Inattention Test. In the other, the stimuli
      were displayed on a large (2x2.4 m) screen and varied in length (48-480 mm) and
      also in location on the screen (left, centre and right). They were presented at
      two viewing distances (0.6 and 1.5 m). Subjects remotely adjusted the position of
      a cursor until it appeared to bisect the stimulus line, using two push-buttons,
      one in each hand. The PD participants (n=18) had a marked asymmetry of motor
      symptoms. They were divided into two groups, those with predominantly left-sided
      motor symptoms (LPD, n=9), and those with predominantly right-sided motor
      symptoms (RPD, n=9). The control group (n=9) were all right-handed. No
      significant differences between the groups were found on the BIT bisection task.
      In contrast, when the stimuli were presented on the screen, LPD subjects showed a
      significant rightward bias in their settings of the cursor, particularly for
      lines on the left and centre of the screen, which was greater, the longer the
      stimulus line. The RPD group bisected lines slightly to the left, in common with
      the control group (pseudo-neglect). In a second experiment, Parkinsonian subjects
      repeated this task, but with the buttons reversed between the hands, so that the
      cursor was moved to the left by the right hand, and vice versa, but the pattern
      of results was the same as in the first experiment. The data suggest a small but
      reliable neglect in left hemiparkinson's disease, which is contralateral to the
      non-dominant (and probably worse affected) hemisphere. The dissociation between
      the response and the bisection error suggests a visuospatial impairment in LPD.

PMID- 11520512
TI  - Surface color from boundaries: a new 'watercolor' illusion.
AB  - A colored line flanking a darker border will appear to assimilate its color onto
      the enclosed white area over distances of up to 45 deg (the Watercolor Effect).
      This coloration is uniform and complete within 100 ms. We found that thin (6
      arcmin), winding inducing lines with different contrasts to the ground are
      generally more effective than thick, straight, and equiluminant lines. Blue and
      red lines induce the strongest effects, but watercolor spreading may also be seen
      with green and yellow. On a white background, color spreading is stronger than on
      chromatic, gray or black backgrounds. Little or no color is perceived when a
      narrow white zone (gap) is inserted in between the two inducing lines. However,
      chains of colored dots instead of continuous lines suffice to produce spreading.
      Edge-induced color is also observed when the two colored lines are presented
      dichoptically, suggesting a cortical origin. The Watercolor Effect described here
      may serve to enhance figure-ground segregation by imparting surface color onto
      the enclosed area, and to promote grouping between distant stimulus elements. As
      a grouping factor, watercolor coloration wins over proximity. Assimilative color
      spreading may arise in two steps: First, weakening of the contour by lateral
      inhibition between differentially activated edge cells (local diffusion); and
      second, unbarriered flow of color onto the enclosed area (global diffusion).

PMID- 11520514
TI  - Biological uncertainties about reproductive cloning.

PMID- 11520515
TI  - Clopidogrel in invasive management of non-ST-elevation ACS.

PMID- 11520516
TI  - Of isolates and isolation: Pseudomonas aeruginosa in adults with cystic fibrosis.

PMID- 11520517
TI  - Clinical decisions: from art to science and back again.

PMID- 11520518
TI  - Handwriting and obsessive-compulsive disorder.

PMID- 11520519
TI  - Gout: diet and uric acid revisited.

PMID- 11520520
TI  - Reforming health care, Saskatchewan style.

PMID- 11520521
TI  - Effects of pretreatment with clopidogrel and aspirin followed by long-term
      therapy in patients undergoing percutaneous coronary intervention: the PCI-CURE
      study.
AB  - BACKGROUND: Despite the use of aspirin, there is still a risk of ischaemic events
      after percutaneous coronary intervention (PCI). We aimed to find out whether, in
      addition to aspirin, pretreatment with clopidogrel followed by long-term therapy
      after PCI is superior to a strategy of no pretreatment and short-term therapy for
      only 4 weeks after PCI. METHODS: 2658 patients with non-ST-elevation acute
      coronary syndrome undergoing PCI in the CURE study had been randomly assigned
      double-blind treatment with clopidogrel (n=1313) or placebo (n=1345). Patients
      were pretreated with aspirin and study drug for a median of 6 days before PCI
      during the initial hospital admission, and for a median of 10 days overall. After
      PCI, most patients (>80%) in both groups received open-label thienopyridine for
      about 4 weeks, after which study drug was restarted for a mean of 8 months. The
      primary endpoint was a composite of cardiovascular death, myocardial infarction,
      or urgent target-vessel revascularisation within 30 days of PCI. The main
      analysis was by intention to treat. FINDINGS: There were no drop-outs. 59 (4.5%)
      patients in the clopidogrel group had the primary endpoint, compared with 86
      (6.4%) in the placebo group (relative risk 0.70 [95% CI 0.50-0.97], p=0.03). Long
      term administration of clopidogrel after PCI was associated with a lower rate of
      cardiovascular death, myocardial infarction, or any revascularisation (p=0.03),
      and of cardiovascular death or myocardial infarction (p=0.047). Overall
      (including events before and after PCI) there was a 31% reduction cardiovascular
      death or myocardial infarction (p=0.002). There was less use of glycoprotein
      IIb/IIIa inhibitor in the clopidogrel group (p=0.001). At follow-up, there was no
      significant difference in major bleeding between the groups (p=0.64).
      INTERPRETATION: In patients with acute coronary syndrome receiving aspirin, a
      strategy of clopidogrel pretreatment followed by long-term therapy is beneficial
      in reducing major cardiovascular events, compared with placebo.

PMID- 11520523
TI  - Cardiotocography only versus cardiotocography plus ST analysis of fetal
      electrocardiogram for intrapartum fetal monitoring: a Swedish randomised
      controlled trial.
AB  - BACKGROUND: Previous studies indicate that analysis of the ST waveform of the
      fetal electrocardiogram provides information on the fetal response to hypoxia. We
      did a multicentre randomised controlled trial to test the hypothesis that
      intrapartum monitoring with cardiotocography combined with automatic ST-waveform
      analysis results in an improved perinatal outcome compared with cardiotocography
      alone. METHODS: At three Swedish labour wards, 4966 women with term fetuses in
      the cephalic presentation entered the trial during labour after a clinical
      decision had been made to apply a fetal scalp electrode for internal
      cardiotocography. They were randomly assigned monitoring with cardiotocography
      plus ST analysis (CTG+ST group) or cardiotocography only (CTG group). The main
      outcome measure was rate of umbilical-artery metabolic acidosis (pH <7.05 and
      base deficit >12 mmol/L). Secondary outcomes included operative delivery for
      fetal distress. Results were first analysed according to intention to treat, and
      secondly after exclusion of cases with severe malformations or with inadequate
      monitoring. FINDINGS: The CTG+ST group showed significantly lower rates of
      umbilical-artery metabolic acidosis than the cardiotocography group (15 of 2159
      [0.7%] vs 31 of 2079 [2%], relative risk 0.47 [95% CI 0.25-0.86], p=0.02) and of
      operative delivery for fetal distress (193 of 2519 [8%] vs 227 of 2447 [9%], 0.83
      [0.69-0.99], p=0.047) when all cases were included according to intention to
      treat. The differences were more pronounced after exclusion of 291 in the CTG+ST
      group and 283 in the CTG group with malformations or inadequate recording.
      INTERPRETATION: Intrapartum monitoring with cardiotocography combined with
      automatic ST-waveform analysis increases the ability of obstetricians to identify
      fetal hypoxia and to intervene more appropriately, resulting in an improved
      perinatal outcome.

PMID- 11520524
TI  - Relation between drug treatment and cancer in hypertensives in the Swedish Trial
      in Old Patients with Hypertension 2: a 5-year, prospective, randomised,
      controlled trial.
AB  - BACKGROUND: Is cancer related to hypertension and blood pressure? Do
      antihypertensive drugs promote cancer? Do antihypertensive drugs protect against
      cancer? We previously analysed the frequency of cardiovascular mortality and
      morbidity in elderly people who participated in the Swedish Trial in Old Patients
      with Hypertension 2 (STOP-Hypertension-2). We have also looked at the frequency
      of cancer in these patients. METHODS: We randomly assigned 6614 elderly patients
      with hypertension (mean age 76 years, median time of follow-up 5.3 years) to one
      of three treatment strategies: conventional drugs (diuretics or b-blockers),
      calcium antagonists, or ACE inhibitors. We matched the patients to the Swedish
      Cancer Registry and compared our findings with expected values based on age, sex,
      and calendar-year-specific reference frequencies for the general Swedish
      population. We also compared the number of cancers between the three treatment
      groups. FINDINGS: At baseline, 607 (9%) patients had previous malignant disease.
      Diagnoses were closely similar to the distribution of cancer types that might be
      seen in elderly patients. During follow-up, there were 625 new cases of cancer in
      590 patients. The frequency of cancer did not differ significantly between the
      treatment strategies, including all cancers and those at individual sites. The
      standardised incidence ratios (SIRs) for all cancers were also close to unity:
      0.92 (95% CI 0.80-1.06) for conventional drugs, 0.96 (0.83-1.10) for calcium
      antagonists, and 0.99 (0.86-1.13) for ACE inhibitors. INTERPRETATIONS: No
      difference in cancer risk was seen between patients randomly assigned to
      conventional drugs, calcium antagonists, or ACE inhibitors. Thus, the general
      message to the practising physician is that more attention should be given to
      getting the blood pressure down than to the risk of cancer.

PMID- 11520525
TI  - Effect of mutations in Pneumocystis carinii dihydropteroate synthase gene on
      outcome of P carinii pneumonia in patients with HIV-1: a prospective study.
AB  - BACKGROUND: Investigators have reported that patients infected with Pneumocystis
      carinii containing mutations in the DHPS (dihydropteroate synthase) gene have a
      worse outcome than those infected with P carinii containing wild-type DHPS. We
      investigated patients with HIV-1 infection and P carinii pneumonia to determine
      if DHPS mutations were associated with poor outcomes in these patients. METHODS:
      We compared presence of mutations at the DHPS locus with survival and response of
      patients to co-trimoxazole or other drugs. FINDINGS: For patients initially given
      co-trimoxazole, nine (14%) of 66 with DHPS mutant died, compared with nine (25%)
      of 36 with wild type (risk ratio50.55 [95% CI=0.24-1.25]; p=0.15). Ten (15%) of
      66 patients with a DHPS mutant did not respond to treatment, compared with 13
      (36%) of 36 patients with the wild type (0.42 [0.20-0.86]; p=0.02). For patients
      aged 40 years or older, four (14%) of 29 with the mutant and nine (56%) of 16
      with the wild type died (0.25 [0.09-0.67]; p=0.005). INTERPRETATION: These
      results, by contrast with those of previous studies, suggest that patients with
      wild-type P carinii do not have a better outcome than patients with the mutant
      when given co-trimoxazole. Our results suggest that presence of a DHPS mutation
      should be only one of several criteria guiding the choice of initial drug
      treatment of P carinii pneumonia in patients with HIV-1 infection.

PMID- 11520526
TI  - Effect of concomitant HIV infection on presentation and outcome of rotavirus
      gastroenteritis in Malawian children.
AB  - BACKGROUND: Rotaviruses represent important causes of severe diarrhoea in early
      childhood. We examined the effect of HIV infection on the presentation and
      outcome of rotavirus gastroenteritis in Malawian children. METHODS: Children
      younger than 5 years who were treated for acute gastroenteritis at the Queen
      Elizabeth Central Hospital in Blantyre from July, 1997, to June, 1999, were
      enrolled. Children with rotavirus diarrhoea, with and without HIV infection, were
      followed up for up to 4 weeks after hospital discharge. Rotavirus disease
      severity (assessed with a 20-point score), duration of rotavirus shedding, and
      seroresponse to rotavirus were compared between HIV-infected and HIV-uninfected
      children. FINDINGS: 786 inpatients (median age 8 months, 271 [34%] of whom were
      HIV-1-infected) and 400 outpatients (median age 9 months, 65 [16%] of whom were
      HIV-infected) were enrolled. Rotavirus was detected less frequently among HIV
      infected children (102 of 336 [30%]) than among HIV-uninfected children (348 of
      850 [41%], (relative risk 0.71 [95% CI 0.53-0.87], p=0.0007). There were no
      differences in rotavirus disease severity for hospitalised children with and
      without HIV infection, but HIV-infected children were more likely to die during
      follow-up (11/50 [22%]) than HIV-uninfected children (0/61, p<0.0001). Of 29 HIV
      infected and 45 HIV-uninfected children who completed follow-up, six (21%) HIV
      infected children shed rotavirus, compared with two (4%) HIV-uninfected children
      (4.66 [1.01-21.51], p=0.05), but shedding was not associated with diarrhoea.
      Three-quarters of children exhibited a four-fold rise of serum IgG or IgA to
      rotavirus, which did not vary by HIV status. INTERPRETATION: Malawian children
      with concomitant HIV infection resolved acute rotavirus infections. Rotavirus
      vaccine safety and immunogenicity in HIV-infected infants should now be
      determined.

PMID- 11520528
TI  - Flash pulmonary oedema.

PMID- 11520529
TI  - Spread of a multiresistant strain of Pseudomonas aeruginosa in an adult cystic
      fibrosis clinic.
AB  - We initiated a prospective surveillance study to investigate possible Pseudomonas
      aeruginosa cross-infection in our cystic fibrosis centre. We characterised
      isolates by pyocin typing and pulsed-field gel electrophoresis. 22 (14%) of 154
      patients with chronic P aeruginosa had isolates with similar and new pyocin and
      pulsed-field gel electrophoresis types. The shared isolates showed unusual
      phenotypic features: they were non-pigmented, non-motile, and resistant to a
      number of antipseudomonal antibiotics. Cross-infection by a multiresistant P
      aeruginosa strain has therefore occurred in patients attending our cystic
      fibrosis centre. We recommend microbiological surveillance in other cystic
      fibrosis centres.

PMID- 11520530
TI  - Superinfection with a transmissible strain of Pseudomonas aeruginosa in adults
      with cystic fibrosis chronically colonised by P aeruginosa.
AB  - Infection with transmissible strains of Pseudomonas aeruginosa can occur in
      uncolonised patients, but cross infection (superinfection) of patients already
      colonised withP aeruginosa has not been reported. With genotypic identification,
      we found superinfection by a multiresistant transmissible strain of P aeruginosa
      in four patients with cystic fibrosis (CF) who were already colonised by unique
      strains of P aeruginosa. No evidence of environmental contamination was found,
      but all patients became superinfected after contact with colonised individuals
      during inpatient stays. Inpatients with CF who are colonised with P aeruginosa
      should be separated by strain type. Such strain typing can only be reliably done
      by genomic methods, but this has resource implications.

PMID- 11520531
TI  - Length of gestation and birthweight in dizygotic twins.
AB  - Despite the longer gestation of girls, their birthweight is less than that of
      boys. Because unlike-sex twins provide a natural situation in which to
      investigate the influence of sex on gestation, we compared birthweight and
      gestation of 1929 same-sex and unlike-sex dizygotic pairs. Length of gestation in
      unlike-sex pairs was similar to that of female same-sex pairs, and significantly
      (0.4 weeks; p=0.02) longer than that of male same-sex pairs. Birthweight of girls
      from unlike-sex pairs was similar to that of girls from same-sex pairs, but boys
      from unlike-sex pairs weighed 78 g more than boys from same-sex pairs (p=0.001).
      These data show that in unlike-sex pairs it is the girl that prolongs gestation
      for her brother, resulting in a higher birthweight than that of same-sex boys.

PMID- 11520532
TI  - Occupational exposure to carbon black and risk of bladder cancer.
AB  - Exposure to carbon black has been linked to risk of lung and bladder cancer. We
      therefore investigated the frequency of these cancers in a group of 2286
      longshoremen who were exposed occupationally to carbon-black dust. We identified
      208 cancers (standardised incidence ratio 96, 95% CI 83-109), 53 lung cancers
      (108, 81-141), and 32 bladder cancers (130, 89-184). Longshoremen exposed to high
      concentrations of carbon black (n=14) had a significantly increased frequency of
      bladder cancer (204, 112-343). We conclude that the increase in bladder cancer in
      longshoremen is probably related to high exposure to carbon black.

PMID- 11520533
TI  - Old drugs to treat new variant Creutzfeldt-Jakob disease.

PMID- 11520534
TI  - Childhood obesity may be related to father's genes.

PMID- 11520535
TI  - Researchers question WHO protocol for treating HIV-infected patients.

PMID- 11520536
TI  - Diet and exercise delay onset of type 2 diabetes, say US experts.

PMID- 11520537
TI  - A marker for melanoma?

PMID- 11520538
TI  - Alternative medicine centre aims for mainstream status.

PMID- 11520539
TI  - China's rural health care gradually worsens.

PMID- 11520540
TI  - Bush supports limited funding for stem-cell research.

PMID- 11520543
TI  - Australia discusses national programme to improve quality of health care.

PMID- 11520544
TI  - Indian mental-health care reviewed after death of asylum patients.

PMID- 11520545
TI  - Belgian surgeon chosen to head International Olympic Committee.

PMID- 11520546
TI  - Decision analysis in patient care.
AB  - To help patients to fully participate in shared decision making is becoming an
      important goal in clinical practice and one which is receiving increasing
      attention in terms of the requisite skills and technological development. We
      discuss the potential application of decision analysis-a specific technology that
      has been introduced into clinical practice but to date only within research
      contexts-and examine the usefulness and feasibility of the technique for
      patients, particularly in settings where clinical presentations are diverse and
      characterised by uncertainty.

PMID- 11520547
TI  - Todd, Hughlings Jackson, and the electrical basis of epilepsy.
AB  - John Hughlings Jackson is widely credited with the first electrical theory of
      epilepsy (1873), which was confirmed by the experimental studies of Hitzig and
      Ferrier. His views are summarised in his famous Lumleian lectures to the Royal
      College of Physicians in 1890. Robert Bentley Todd, however, had earlier
      developed an electrical theory of epilepsy, which he presented in his own
      brilliant Lumleian lectures to the Royal College of Physicians in 1849. Todd was
      influenced by the electrical discoveries of his contemporary, Michael Faraday,
      and thought of the brain as having battery like properties that led to the sudden
      discharge of electrical energy (nervous force) in epilepsy. Unlike Hughlings
      Jackson, Todd was an anatomist and physiologist as well as a physician, and he
      did his own electrical experiments in rabbits to prove his theory, something
      Hughlings Jackson, who relied on Ferrier for scientific and experimental support,
      could never have done. There is no mention of Todd's Lumleian lectures in
      Hughlings Jackson's later lectures and writings, nor in those of Hitzig or
      Ferrier. Todd's remarkable observations and lectures, and his electrical theory
      of epilepsy deserve to be drawn to the attention of the medical and scientific
      community.

PMID- 11520548
TI  - Inappropriate drug donations: the need for reforms.

PMID- 11520550
TI  - Economic sanctions on Yugoslavia.

PMID- 11520549
TI  - The Global Health Fund: moral imperative or industry subsidy?

PMID- 11520557
TI  - A titbit.

PMID- 11520558
TI  - Interphase detection of immunoglobulin heavy chain gene translocations with
      specific oncogene loci in 173 patients with B-cell lymphoma.
AB  - To detect immunoglobulin heavy chain (IGH) gene translocations with specific
      oncogene loci, we established an interphase cytogenetic approach using double
      color fluorescence in situ hybridization (DC-FISH), which we used to analyze 173
      patients with B-cell lymphoma. DC-FISH using the IGH gene (14q32.3) in
      combination with c-MYC (8q24.1), BCL1 (11q13.3), BCL2 (18q21.3), BCL6 (3q27), and
      PAX-5 (9p13) gene probes detected IGH translocations in 70 (40.5%) of 173
      patients. The partner genes involved in IGH translocations were identified in 56
      (80%) of 70 patients, and fusion of the IGH gene with specific oncogenes was
      detected in 53 of 56 patients, particularly in interphase nuclei of 28 patients
      for whom cytogenetic analysis was not informative. The most common partner gene
      was BCL2 (19 patients; 27% of IGH translocation-positive patients), followed by
      BCL6 (16; 23%), BCL1 (11; 16%), c-MYC (7; 10%), and PAX-5 (2; 3%). These
      oncogenes were closely associated with subtypes of B-cell lymphoma. The other
      partners were 19q13 (BCL3), 6p25 (MUM1/IRF4), 1q36, and chromosome 8 identified
      in one patient each. Six of the nine patients with add(14)(q32) showed a BCL6/IGH
      translocation. Double translocations of the IGH gene were found in three
      patients; c-MYC+BCL1, c-MYC+BCL2, and c-MYC+BCL6 in each one. Interphase FISH
      using specific IGH-translocation probes is valuable for defining clinically
      meaningful subgroups of B-cell lymphoma.

PMID- 11520559
TI  - Chromosomal aberrations in neuroblastoma cell lines identified by cross species
      color banding and chromosome painting.
AB  - We have studied cytogenetic rearrangements in karyotypes of five neuroblastoma
      cell lines [SK-N-AS, SK-N-SH, SH-SY5Y, SK-N-MC, SMS-KCNR] by G-banding, cross
      species color banding (RxFISH), and fluorescence in situ hybridization (FISH)
      with chromosome painting probes. Each neuroblastoma cell line had unique modal
      karyotypic characteristics and showed a variable number of numerical and
      structural clonal cytogenetic aberrations. The number of rearranged chromosomes
      in SK-N-AS, SK-N-SH, SH-SY5Y, SK-N-MC, and SMS-KCNR was 11, 3, 7, 14 (tetraploid,
      20-21), and 6, respectively. The origins of abnormal chromosomes were effectively
      analyzed by RxFISH and FISH with multiple chromosome painting probes. The
      chromosomal origin of the homogeneously staining region in SH-SY5Y was identified
      as coamplification of chromosome bands 2p13 and 2p24 by chromosome
      microdissection and FISH. The non-random rearrangements of chromosomes were
      determined on 1p34 approximately p36, 6q16 approximately q21, 8q24, 9q34, 11q13
      approximately q23, 16q23 approximately q24, 17q21, and 22q31. These results may
      provide useful information for further molecular characterization of
      neuroblastoma.

PMID- 11520560
TI  - Characterization of t(11;19)(q23;p13.3) by fluorescence in situ hybridization
      analysis in a pediatric patient with therapy-related acute myelogenous leukemia.
AB  - This case presents a Caucasian girl diagnosed with early pre-B cell acute
      lymphoblastic leukemia at age 2 years. The only chromosomal anomaly detected in
      her bone marrow cells at this time was an add(12p). By age 4 years, she had a
      bone marrow and central nervous system (CNS) relapse of ALL and was treated with
      chemotherapy that included etoposide. She was in complete remission for 2 years
      following chemotherapy with etoposide, but later developed therapy-related acute
      myeloid leukemia (t-AML). At this time, a t(11;19)(q23;p13.3) rearrangement was
      detected in her bone marrow cells. The AML relapsed again 1 year after allogeneic
      bone marrow transplant (BMT). The presence of a chromosome 11 abnormality
      involving band 11q23 in this patient suggests that the transformation from ALL to
      t-AML was a consequence of etoposide included in her chemotherapy. Studies have
      shown that the 11q23 breakpoint in the t(11;19) rearrangement is consistent, and
      involves the MLL gene in t-AML patients. However, the breakpoint in 19p is
      variable in that it could be located either at 19p13.1 or 19p13.3 and thus could
      involve either of two genes: ELL (11-19 lysine-rich leukemia gene) on 19p13.1 or
      ENL (11-19 leukemia gene) on 19p13.3. In this study, the t(11;19)(q23;p13.3) was
      further characterized and the breakpoint regions were defined by fluorescence in
      situ hybridization (FISH) analysis.

PMID- 11520561
TI  - High frequency of allelic imbalance at regions of chromosome arm 8p in ovarian
      carcinoma.
AB  - Progressive genetic changes such as the inactivation of tumor suppressor genes
      (TSG) are thought to play an important role in the initiation and progression of
      ovarian cancer. Frequent nonrandom allelic imbalance (AI) at 8p11-p21 and 8p22
      pter suggests the existence of TSGs that may be involved in the carcinogenesis of
      several human malignancies. We investigated 70 ovarian tumors with 11 highly
      polymorphic markers spanning 8p12-p21 and 8p22-pter to produce an AI map of 8p in
      epithelial ovarian cancer. Allelic imbalance was demonstrated in 54 tumors (77%),
      most frequently occurring at D8S136 (54%) and at D8S1992 (55%). Poorly
      differentiated and advanced stage cancers were more often affected by AI (G1+G2
      vs. G3; 20% vs. 66%; stage I+II vs. III+IV, 36% vs. 54%, P<.001; Kruskal-Wallis
      test) than well differentiated and early stage tumors. There was no relationship
      between histological subtype and AI. Smallest regions of overlap (SRO) were
      delineated by analyzing 38 tumors with partial AI. This study provides compelling
      evidence for the involvement of TSGs on the short arm of chromosome 8, at 8p12
      p21 and at 8p23 in the development and progression of epithelial ovarian cancer.

PMID- 11520562
TI  - Clonal chromosomal aberrations accompanied by strong telomerase activity in
      immortalization of human B-lymphoblastoid cell lines transformed by Epstein-Barr
      virus.
AB  - Human B-lymphoblastoid cell lines transformed by Epstein-Barr (EBV-LCLs) are
      considered to be immortalized, although most of them show a normal diploid
      karyotype. Recently, we and others have shown that only part of EBV-LCLs is
      immortalized by developing strong telomerase activity that stabilizes the
      telomeres. In this study, we investigated the change in karyotypes during
      immortalization. All the eight immortalized cell lines developed clonal
      chromosomal aberrations accompanied by the development of strong telomerase
      activity. Interestingly, abnormal chromosomes were not shared among the
      immortalized cell lines. These results strongly suggest that chromosomal
      rearrangements and induction of strong telomerase activity are two events that
      take place in parallel in the process of immortalization of EBV-LCLs, and
      indicate that EBV-LCLs are clearly divided into two distinct groups, pre-immortal
      cell lines mostly with a normal diploid karyotype and post-immortal cell lines
      with a clonally abnormal karyotype.

PMID- 11520563
TI  - Differential gene expression associated with tumorigenicity of cultured green
      turtle fibropapilloma-derived fibroblasts.
AB  - Fibroblast cell lines derived from normal skin and experimentally induced
      fibropapillomas of green turtles (Chelonia mydas), were propagated in vitro and
      tested for tumorigenicity in immunodeficient mice. Differential display RT-PCR
      was used to identify differences in messenger RNA expression between normal and
      tumorigenic fibropapillomatosis (FP)-derived fibroblasts from the same
      individual. Four unique products that were apparently overexpresed in FP and
      three that were apparently underexpressed were cloned and sequenced. Differential
      expression was confirmed for three products by Northern blotting. Two
      overexpressed products showed extensive sequence matches to the known mammalian
      cellular genes, beta-hexosaminidase and chain termination factor. The product
      that was underexpressed in FP showed homology with mammalian thrombospondin, a
      known tumor-suppressor gene and an inhibitor of angiogenesis. All of the partial
      gene sequences identified are novel and will require full length cDNA sequencing
      to further analyze their identities. These results, however, provide the
      foundation for further investigation to determine the role of each of these gene
      products in FP pathogenesis and cellular transformation. The potential for some
      of these products to serve as biomarkers for FP is discussed.

PMID- 11520564
TI  - Mutations spanning P53 exons 5-9 detected by non-isotopic RNAse cleavage assay
      and protein expression in human colon cancer.
AB  - The non-isotopic assay (NIRCA), based on the observation that RNAse is able to
      specifically cleave a single mismatch in RNA/RNA duplexes, has been recently
      proposed to detect p53 mutations. To verify the use of this method as a valid
      screening for P53 mutations in a routinely collected cancer series, we used this
      assay on 3 cases with normal and 5 cases with abnormal P53 expression detected by
      Western blots. In all cases, P53 exons 5-6, 7 and 8-9 regions were analyzed.
      There were mutations only in the five overexpressed cases: two cases showed
      mutations in exon 5, one between intron 6 and exon 6 and two in the region
      spanning exons 8 and 9. Our experience showed NIRCA to be fast, reliable and
      providing the ability to study long target regions in a single step, thus making
      this assay useful for genetic screenings.

PMID- 11520565
TI  - Therapy-related refractory anemia with ringed sideroblasts in chronic lymphocytic
      leukemia. involvement of 3q21 region.
AB  - Therapy-related myelodysplastic syndrome/acute myelogenous leukemia (t-MDS/AML)
      is extremely rare in chronic lymphocytic leukemia (CLL) despite extensive use of
      alkylating agents. We present a case of heavily treated CLL with resultant
      therapy-related refractory anemia with ringed sideroblasts (RARS). A complex
      cytogenetic abnormality including involvement of 3q21 was detected and to our
      knowledge, is the first report of a RARS case with a 3q21 abnormality.

PMID- 11520566
TI  - Comparative genomic hybridization reveals non-random chromosomal aberrations in
      early preinvasive cervical lesions.
AB  - We performed CGH analysis on 34 cervical lesions, which included 8 cases of
      koilocytosis, 6 mild dysplasias and 20 moderate dysplasias. Chromosome
      aberrations were detected in 11 cases of which 9 were moderate dysplasias. A
      total of 55 chromosome arms were involved. The most frequent aberrations were
      losses of 5p and Xq, each of which was present in 5/34 cases. Gain of 3q was
      detected in two moderate dysplasias. This aberration is the most frequent copy
      number change in advanced-stage cervical carcinoma. A considerable number of the
      aberrations found in the preinvasive cases of this study are frequently present
      in invasive cervical tumors. The presence of apparently non-random chromosome
      aberrations in early preinvasive cervical lesions has not previously been
      described.

PMID- 11520567
TI  - Amplification of 3q26 approximately qter correlates with tumor progression in
      head and neck squamous cell carcinomas.
AB  - Biological characteristics of malignant tumors including head and neck squamous
      cell carcinoma (HNSCC) are greatly affected by genetic alterations. However, the
      relationship between chromosomal aberrations and pathologic tumor stage in HNSCC
      has not been elucidated. In 32 patients, DNA sequence copy number aberrations
      (DSCNA) were surveyed by comparative genomic hybridization (CGH) combined with a
      microdissection method. The average number of DSCNA was 15.3 per tumor and
      increased with tumor stage (P<.05). DNA copy number gain was detected at 3q26
      approximately qter in 29 tumors (91%), and 13 of these tumors displayed marked
      DNA amplification. Tumor stage was linked with this amplification (P<.05). The
      increase in DSCNA and amplification of 3q26 approximately qter are likely to be
      useful markers for estimating tumor progression in HNSCC.

PMID- 11520568
TI  - Minimal regions of chromosomal imbalance in retinoblastoma detected by
      comparative genomic hybridization.
AB  - Mutation of both alleles of the retinoblastoma gene (RB1) initiate oncogenesis in
      developing human retina, but other common genomic alterations are present in the
      tumors. In order to sublocalize the altered genomic regions, 50 retinoblastoma
      tumors were examined by comparative genomic hybridization (CGH). The minimal
      regions most frequent gained were 1q31 (52%), 6p22 (44%), 2p24-p25 (30%) and
      13q32-q34 (12%). The minimal region most frequently lost was 16q22 (14%). The
      overall total number of gains or losses evident on CGH was significantly greater
      in those tumors with either or both 6p or 1q gain, than in tumors with neither 6p
      nor 1q gain suggesting that chromosomal instability may be associated with
      acquisition of these changes. Genes mapping to 6p22 and 1q31 may be important in
      tumor development in retina subsequent to the loss of RB1 alleles.

PMID- 11520569
TI  - Sinonasal angiosarcoma with marrow involvement at presentation mimicking
      malignant lymphoma: cytogenetic analysis using multiple techniques.
AB  - Angiosarcoma of the head and neck most commonly involves the skin of the scalp or
      face; primary involvement of the sinonasal region is exceedingly rate. We report
      a patient with sinonasal angiosarcoma who showed marrow involvement at
      presentation. Marrow aspiration smears showed many large, often segregated blast
      like cells, mimicking malignant lymphoma. However, trephine biopsy revealed
      formation of anastomosing vascular spaces by the tumor cells and immunoreactivity
      for CD31, supporting a diagnosis of angiosarcoma. DNA ploidy analysis showed an
      apparent diploidy. Nevertheless, conventional cytogenetics demonstrated very
      complex chromosomal abnormalities with the presence of multiple hypodiploid
      clones, together with several near-triploid to near-tetraploid clones showing
      structural abnormalities involving chromosomes 1, 3, 4, 9, 14, 16, 17, 18, and
      22. The identification of these karyotypic changes has been facilitated by the
      application of comparative genomic hybridization and spectral karyotyping.

PMID- 11520570
TI  - Oligoclonal expansion of alphabeta T lymphocytes in Epstein-Barr virus-associated
      hemophagocytic lymphohistiocytosis with abnormal karyotypes.
AB  - We observed a fatal case of Epstein-Barr virus (EBV)-associated hemophagocytic
      lymphohistiocytosis (HLH) with an abnormal karyotype. Increased levels of
      alphabeta T cells of the patient were investigated using an inverse polymerase
      chain reaction (PCR) of the T-cell receptor variable region gene, followed by
      Jbeta-PCR and single-strand conformation polymorphism (SSCP) to confirm the
      clonality of specific alphabeta-T cell subsets. A high frequency (>15%) was
      recognized in Vbeta9 at onset, but not in any Vbeta and Valpha families 2 weeks
      after chemotherapy. High levels (>20%) of some Jbeta genes were detected in all
      Vbeta families investigated, and the predominant bias of the Jbeta2 gene relative
      to the Jbeta1 gene (86.1% versus 13.9% at onset, and 77.4% versus 23.5% after
      chemotherapy) was recognized in pan-alphabeta T cells. When each Vbeta-Jbeta
      fragment was compared among the samples at onset and after chemotherapy by SSCP
      analysis, several distinct bands were observed that indicate a clonal evolution.
      Thus, the findings suggest that some of the alphabeta T cell clones could be
      associated with abnormal karyotypes in EBV-HLH. The present findings provide
      molecular evidence of the presence of oligoclonal T cells in pan-alphabeta-T
      cells and clonal evolution during a short clinical course in EBV-HLH with
      abnormal karyotypes.

PMID- 11520571
TI  - Chronic myeloid leukemia with a rare variant Philadelphia translocation:
      t(9;10;22)(q34;q22;q11).
AB  - We report a 59-year-old, male, chronic myeloid leukemia patient with a rare
      variant Philadelphia (Ph) translocation t(9;10;22)(q34;q22;q11). Fluorescence in
      situ hybridization with whole chromosome paints was used to confirm the
      cytogenetic findings. With a BCR/ABL-specific probe, the known rearrangement on
      the derivative chromosome 22 was found. The prognostic implications as well as
      the relevance of the additional breakpoint region 10q22 are discussed.

PMID- 11520572
TI  - Detection of translocations involving the HOX11/TCL3-locus in 10q24 by interphase
      fluorescence in situ hybridization.
AB  - The t(10;14)(q24;q11) and its variant t(7;10)(q35;q24), which are recurrent in
      acute T-cell leukemia, lead to activation of the HOX11/TCL3-gene in chromosomal
      region 10q24 by juxtaposing this gene to one of the T-cell receptor loci. In the
      present study, we established a diagnostic assay for detecting these
      translocations by interphase fluorescence in situ hybridization (FISH). BAC
      clones flanking the HOX11/TCL3-locus were obtained from a fingerprinted BAC
      contig of chromosomal region 10q24. BAC clones located proximal and distal of the
      HOX11/TCL3-locus were differently labeled and applied to interphase-FISH in seven
      normal controls and eight T-cell neoplasms with t(10;14)(q24;q11) or
      t(7;10)(q35;q24). In over 1600 nuclei of controls, a considerable split defined
      as separation of each one signal for the proximal and distal probe by more than
      three times the signal diameter was observed in only one cell. In contrast, all T
      cell neoplasms with t(10;14) or t(7;10) contained at least 47% of nuclei with a
      signal split indicating a breakpoint in the HOX11/TCL3-locus. Thus, the
      established double-color FISH approach provides a new reliable and routinely
      applicable tool for diagnosing breakpoints in the HOX11/TCL3-locus.

PMID- 11520573
TI  - Significance of intron 6 sequence variations in the TP53 gene in Li-Fraumeni
      syndrome.
AB  - Many polymorphisms have been reported in the TP53 gene. Some of these are within
      the coding region, and may affect the function of the p53 protein, others are
      within introns or non-coding regions, and their significance is unclear.
      Recently, a number of publications have claimed that polymorphisms within intron
      6 are responsible for inherited predisposition to childhood malignancies,
      familial breast cancer, and Li-Fraumeni syndrome (LFS). We find no evidence for
      intron 6 sequence variants predisposing to LFS in our cohort of families and,
      furthermore, we show that some of the conclusions of other groups cannot be
      supported by data from our analysis.

PMID- 11520574
TI  - Analysis of p73 gene in meningiomas with deletion at 1p.
AB  - The p73 gene has been mapped to 1p36.33, a chromosome region that is frequently
      deleted in a wide variety of neoplasms including meningiomas. The protein encoded
      by p73 shows structural and functional similarities to p53 and may thus represent
      a candidate tumor suppressor gene. To determine whether p73 is involved in the
      development of meningiomas, we examined 30 meningioma samples with proven 1p
      deletion for mutations of p73. Sequence analysis of the entire coding region of
      the p73 gene revealed previously reported polymorphisms in eight cases. A tumor
      specific missense mutation as a result of an A-to-G transition with an Asn204Ser
      change was found in one meningioma that nevertheless retained the normal allele.
      These results suggest that if p73 plays a role in meningioma carcinogenesis, it
      must be in a manner different from the Knudson two-hit model.

PMID- 11520575
TI  - The human T-lymphotropic viruses: bench and bedside progress.

PMID- 11520576
TI  - HTLV-1 structural proteins.
AB  - HTLV-1 structural proteins do not appear to ensure virus transmission as
      efficiently as most other retrovirus structural proteins do, whereas all other
      retroviruses can be transmitted via either free virions or cell-to-cell contacts,
      infection by HTLV-1 by free virions is very inefficient, and effective infection
      requires the presence of HTLV-1 infected cells. This characteristic feature of
      HTLV-1 provides a unique tool which can be used to analyse retrovirus cellular
      transmission in the absence of simultaneous cell-free infection. Here we
      summarise what is known about HTLV-1 structural proteins and identify the
      questions about these proteins which remain to be answered.

PMID- 11520577
TI  - Soluble recombinant HTLV-1 surface glycoprotein competitively inhibits syncytia
      formation and viral infection of cells.
AB  - Efficient entry into, and infection of, human cells by human T-cell leukaemia
      virus type-1 (HTLV-1) is mediated by the viral envelope glycoproteins, gp46 and
      gp21. The gp46 surface glycoprotein binds to an as yet unidentified cell surface
      receptor, thereby, allowing the gp21 transmembrane glycoprotein to initiate
      fusion of the viral and cellular membranes. In the absence of membrane fusion
      viral penetration and entry into the host cell cannot occur. The envelope
      glycoproteins are also a major target for neutralising antibodies and cytotoxic T
      lymphocytes following a protective immune response, and represent ideal
      constituents for a recombinant HTLV-1 vaccine. Given the importance of the
      envelope proteins in HTLV-1 pathogenesis there is increasing interest in
      obtaining sufficient quantities of these proteins for biochemical, biophysical
      and biological analyses. We have now developed a system for production of large
      amounts of a glycosylated and functional form of soluble recombinant gp46
      (sRgp46), and have used this recombinant material for analysis of envelope
      function and receptor binding activity. We find that, the sRgp46 molecules
      expressed in our system are immunologically indistinguishable from the native
      virally expressed surface glycoproteins; that sRgp46 binds to T-cells in a dose
      dependent and saturable manner; and that cell surface binding by sRgp46 can be
      inhibited by neutralising antibodies. Importantly, we demonstrate that these
      sRgp46 molecules potently inhibit syncytia formation and viral infection of
      target cells, and that regions outwith the SU domain of envelope are not required
      for binding to target cells or for inhibiting membrane fusion. The sRgp46
      produced in our study will provide new opportunities to investigate envelope
      receptor interactions, and will be of utility in defining the conformationally
      sensitive antigenic determinants of the HTLV-1 surface glycoprotein.

PMID- 11520578
TI  - Expression and functional properties of proteins encoded in the x-II ORF of HTLV
      I.
AB  - With the aim of identifying viral proteins that contribute to the distinctive
      properties of HTLV-I biology and pathogenicity, several laboratories have
      investigated the coding potential of the X region of the genome, which includes
      five partially overlapping open reading frames (ORFs). We and others have shown
      that, in addition to the essential regulatory proteins Rex and Tax, a number of
      accessory proteins encoded in the X region can be produced by alternative
      splicing and multicistronic translation. One X region ORF, termed X-II, produces
      two protein isoforms named Tof/p30II and p13II, which are expressed from a doubly
      and singly-spliced mRNA, respectively. Initial functional analyses demonstrated
      that Tof/p30II is a nucleolar/nuclear protein that possesses a region capable of
      binding to RNA, and p13II is a mitochondrial protein that alters the morphology
      and function of this organelle. Together with data from other laboratories
      demonstrating the production of antibodies and CTL against x-II ORF products in
      HTLV-I infected subjects and the requirement of this ORF for efficient viral
      replication in vivo, these findings suggest that further characterization of
      Tof/p30II and p13II will yield insight into remaining undefined aspects of HTLV-I
      pathogenicity and replication.

PMID- 11520579
TI  - Oligonucleotide mapping of the core genomic RNA dimer linkage in human T-cell
      leukaemia virus type-1.
AB  - We have previously mapped the sequences required for dimerisation of the 5'
      leader of the human T-cell leukaemia virus type-1 (HTLV-1) genome. The smallest
      sequence necessary and sufficient for dimer formation, in vitro, was ascertained
      to be a 37 nucleotide (nt) region downstream of the splice donor and just
      upstream of the primer binding site. Deletion of a 32 base-pair sequence
      encompassing this region within the provirus was associated with a minor decrease
      in infectivity of the virus in an in vitro system. To further map and help
      elucidate the nature of the dimer linkage, we used RNA and DNA oligonucleotide
      competition assays to define the nucleotides involved. These experiments revealed
      that a 14 nt sequence containing a potential stem loop structure, formed from a
      palindromic sequence, is important for dimer formation. This was confirmed by the
      ability of this RNA sequence to form heterodimers with larger RNA transcripts
      from the same region, while sequences lacking this motif could not. RNA
      transcripts containing the reverse sequence, the same nucleotides in a random
      arrangement, and complementary DNA oligos, all failed to form heterodimers with
      the 14 nt sequence. The primary dimer initiation site of HTLV-1 has thus been
      located to a 14 nt palindrome containing sequence, and dimerisation is shown to
      be dependent on specific sense-sense RNA interactions.

PMID- 11520580
TI  - Functional changes in astrocytes by human T-lymphotropic virus type-1 T
      lymphocytes.
AB  - The human T-lymphotropic virus type-1 (HTLV-1) is the causative agent of a
      chronic progressive myelopathy (TSP/HAM) in which lesions of the central nervous
      system (CNS) are associated with infiltration of HTLV-1-infected T-cells. In a
      model that mimics the interaction between glial and T-cells, we show that
      transient contact with T-lymphocytes chronically infected with HTLV-1 induce
      profound metabolic alterations in astrocytes. Within the first week post-contact,
      an overall activation of astrocyte metabolism was observed as assessed by
      enhanced uptake of glutamate and glucose, and lactate release. In contrast,
      longer examination showed a reduced astrocytic accumulation of glutamate. The
      time course of the change in glutamate uptake was in fact biphasic. Previous
      observations indicated that HTLV-1 protein Tax-1 was involved in this delayed
      decrease, via the induction of TNF-alpha. The expression of the glial glutamate
      transporters, GLAST and GLT-1 decreased in parallel. These decreases in glutamate
      uptake and transporters' expression were associated with an imbalance in the
      expression of the catabolic enzymes of glutamate, GS and GDH, presumably due to
      Tax-1. Given the fact that impairment of glutamate management in astrocytes is
      able to compromise the functional integrity of neurons and oligodendrocytes, our
      results altogether give new insights into the physiopathology of TSP/HAM.

PMID- 11520581
TI  - Efficacy of 3'-azido 3'deoxythymidine (AZT) in preventing HTLV-1 transmission to
      human cord blood mononuclear cells.
AB  - The present study investigated the effect of 3'-azido 3'deoxythymidine (AZT)
      treatment on in vitro infection of human cord blood mononuclear cells (CBMCs)
      exposed to HTLV-1 by cocultivation with the MT-2 cell line. Cultures of CBMCs
      were grown in IL-2 and were either left untreated or were treated with
      concentrations of AZT ranging from 0.0078 to 32 microM. HTLV-1-infected cultures
      were monitored at different times of culture by evaluating proliferation
      activity, cell growth and the presence and expression of HTLV-1 genes. Results
      showed that untreated cultures infected with HTLV-1 were able to grow for several
      weeks, while those treated with AZT at 0.03 microM or higher concentrations were
      limited in their growth capacity. Moreover, the addition of AZT at the moment of
      infection significantly inhibited cell proliferation in a dose-dependent fashion.
      In the presence of AZT, detection of proviral DNA and, more remarkably, viral RNA
      expression were clearly reduced. In addition, treatment with AZT resulted in a
      noticeable decrease in Tax protein expression. Using treatment with relatively
      low doses of AZT, effective in exerting an antiviral action, cytotoxicity on
      CBMCs was not observed, whereas higher doses induced apoptosis in uninfected
      CBMCs. These data show that CBMCs are protected by AZT against HTLV-1
      transmission even at low, non-toxic doses.

PMID- 11520582
TI  - Treatment of adult T-cell leukaemia/lymphoma: current strategy and future
      perspectives.
AB  - Human T-cell leukaemia virus type I (HTLV-I) associated adult T-cell
      leukaemia/lymphoma (ATL) carries a very poor prognosis due to an intrinsic
      resistance of leukaemic cells to conventional or even high doses of chemotherapy
      and to an associated severe immunosuppression. Therefore, the potential role of
      conventional chemotherapy, high dose chemotherapy with autologous or allogeneic
      bone marrow transplantation remains to be defined. Important progress was
      achieved in the treatment of ATL with the combination of zidovudine (AZT) and
      interferon-alpha (IFN) which produces a high response rate in ATL patients with
      minimal side effects. This treatment seems to prolong the survival of patients
      much more than intensive chemotherapy. The success of this potentially anti
      retroviral approach in the treatment of ATL suggests the existence of continuous
      HTLV-I replication in vivo. These encouraging results may be improved by the use
      of higher doses of AZT and IFN combined with other anti-retroviral agents.
      However, since cure seems still elusive, new therapeutic approaches or new
      combinations are required. For example, biological mediators such as retinoid
      acid, which induces apoptosis of ATL cells in vitro, may reduce drug resistance
      and stimulates immunity to restore anti-tumour activity against ATL cells.
      Alternatively, immunotherapy with anti-interleukin-2 receptor monoclonal
      antibodies or injection of cytotoxic T-cells directed against virus antigens
      could be interesting approaches which may merit further investigations in the
      near future. Finally, the recent demonstration that the combination of arsenic
      trioxide (As) and IFN induces a specific degradation of the viral transactivator
      Tax followed by cell cycle arrest and apoptosis of HTLV-I positive cells may
      constitute a valuable addition to ATL treatment.

PMID- 11520583
TI  - The effect of antiretroviral therapy on HTLV infection.
AB  - No effective treatment for TSP/HAM has been described so far. Interventions with
      corticosteroids, plasmapheresis, interferon and, more recently, with
      antiretroviral drugs have been tried with poor results. The main HTLV replication
      mechanism is thought to be through clonal expansion of HTLV-infected cells, which
      excludes the involvement of the reverse transcriptase (RT) enzyme. However, a
      virological and clinical improvement has been noticed in HTLV-I carriers
      suffering from TSP/HAM receiving zidovudine or lamivudine. Herein, we describe
      the virological and clinical outcome in two TSP/HAM patients infected with HTLV-I
      treated with zidovudine plus lamivudine, and in two HTLV-II/HIV-1 co-infected
      patients receiving triple combinations including lamivudine. While, one TSP/HAM
      patient experienced a 2 log decrease in HTLV-I proviral load, an increase of 1
      log was observed in another patient after several months of treatment with
      zidovudine plus lamivudine. The two HTLV-II/HIV-1 co-infected patients showed an
      initial increase in HTLV-II proviral load after beginning HAART followed by a
      slight decline a few months later. Plasma HIV-1 RNA fell to <50 copies/ml in both
      patients after beginning therapy. None of the four HTLV positive patients
      developed genetic changes at the conserved YMDD domain within their respective RT
      genes, which could be related to lamivudine resistance. No clinical improvement
      was observed in one TSP/HAM patient after more than 1 year on treatment with
      nucleoside analogues. The inhibition of the HTLV RT along with the cytostatic
      effect of some nucleoside analogues, including zidovudine, could reduce HTLV
      replication, and therefore reduce HTLV proviral load. The clinical consequences
      of this effect need to be further examined.

PMID- 11520584
TI  - Pooling of samples for seroepidemiological surveillance of human T-cell
      lymphotropic virus types I and II.
AB  - We evaluated a straight forward pooling strategy for antibody screening of HTLV
      I/II, using panels of sera from various parts of the world including a total of
      43 HTLV-I and 54 HTLV-II positive specimens. Four antibody screening assays were
      included in the evaluation: the HTLV-I/II GE 80/81 (Murex Diagnostics), the HTLV
      I/HTLV-II Ab Capture ELISA (Ortho Diagnostics), the HTLV-I/II ELISA 3.0 (Genelabs
      Diagnostics) and the Serodia HTLV-I (Fujirebio). The Murex and Ortho assays
      represent a new generation of HTLV screening tests with a sandwich format
      incorporating both HTLV-I and HTLV-II synthetic and/or recombinant peptide
      antigens. The Genelabs assay is an indirect ELISA with recombinant HTLV-I and -II
      antigens and Serodia is a particle agglutination assay with HTLV-I whole viral
      lysate. Each HTLV-positive sample was included in pools of 1/1 up to 1/16, in two
      fold steps made in normal HTLV-negative blood donor serum from one up to nine
      donors. For HTLV-I, with the exception of one false negative sample in dilution
      1/16 with Genelabs ELISA, all assays were positive at all dilutions. The Murex
      assay had absorbance values at maximum levels for all samples at all dilutions.
      The other assays had gradually decreasing absorbance values although clearly
      above cut-off. For HTLV-II, the Murex assay correctly detected all samples to
      dilution 1/16 despite gradually decreasing signals. The Serodia assay had 100%
      sensitivity to dilution 1/4 while at 1/8 and 1/16 it decreased 82 and 80%,
      respectively. The Genelabs ELISA had gradually decreasing sensitivity for HTLV-II
      from 98 (1/1) to 33% (1/16) while the Ortho assay detected all specimens at all
      dilutions in a limited set of samples tested. Taken together, this evaluation has
      shown that pooling of samples may be an appropriate strategy for serosurveillance
      of HTLV. It is, however, crucial to limit the number of samples and to choose
      assays that allow the dilution caused by the pooling. Using the best performing
      assays in this evaluation for pools of e.g. five samples would leave a reasonable
      safety margin.

PMID- 11520586
TI  - Gingival recession-its significance and management.
AB  - OBJECTIVES: To review the prevalence and current concepts of the mechanisms and
      aetiology of gingival recession and present the principles of assessment and
      management of the patient with gingival recession. DATA AND SOURCES: The
      literature was searched for review and original research papers relating
      prevalence, mechanisms, aetiology, assessment, and treatment of gingival
      recession using Medline and manual tracing of references cited in key papers
      otherwise not elicited. STUDY SELECTION: Studies with gingival recession as focus
      and pertinent to key aspects of review. RESULTS: Gingival recession is a common
      condition and its extent and prevalence increase with age. Many factors including
      trauma and periodontal disease have a role in its aetiology. The patient may
      develop signs and symptoms including pain from exposed dentine, root caries and
      aesthetic concerns. Management of gingival recession requires thorough patient
      assessment, identification of aetiological factors, and recording and monitoring
      of the extent and severity of the condition. Treatment should be directed at
      prevention of further progression and the control of symptoms and disease. The
      patient's aesthetic concerns should be appreciated. Surgical treatment of
      recession may be indicated to cover exposed root surfaces. Many surgical
      techniques have been described with varied reported clinical effectiveness.
      CONCLUSIONS: Gingival recession should be thoroughly assessed and evaluated in
      order to offer the most suitable management.

PMID- 11520587
TI  - The measurement and prevention of erosion and abrasion.
AB  - OBJECTIVES: To develop a reproducible method to measure tooth wear and assess the
      protection given by dentine bonding agents in an erosive/abrasive wear regime.
      METHODS: Seal and Protect (Dentsply, UK) and Optibond Solo (Kerr, UK) were each
      applied to 20 extracted teeth and subjected to 3000 cycles in a reciprocating
      erosion/abrasion wear machine. A further 20 teeth, without protection, were
      subjected to the same wear regime and were either brushed in water or immersed in
      acid. Impressions were taken by a standardised technique and were scanned with a
      non-contacting laser profilometer. The amount of erosion was measured at the same
      co-ordinates before and after erosion using 2mm diameter metal discs as reference
      points. RESULTS: The amount of wear on Seal and Protect had a mean 24.8 microm
      (SD 57.4 microm) and for Solo it was 1.4 microm (24.5 microm), and this
      difference was statistically significant (p=0.02). There was no statistically
      significant difference in the wear measured on the teeth brushed in water or
      immersed in acid. The wear measured on the unprotected teeth was 243 microm (SD
      120 microm) and was statistically significantly different to the protected
      surfaces (p=0.001). CONCLUSION: Both Seal and Protect and Solo protected the
      teeth in this wear regime and the technique could be used clinically for patients
      with uncontrolled dental erosion.

PMID- 11520588
TI  - The reasons for the extraction of various tooth types in Scotland: a 15-year
      follow up.
AB  - OBJECTIVES: The aim of this survey was to investigate the reasons for extraction
      of the various tooth types in Scotland. This study replicated one which was
      undertaken 15 years earlier. A further aim, therefore, was to identify any
      changes in the frequency of extraction of each tooth type in the 15 years between
      the two studies. METHODS: The names of every fourth dentist on the list of the
      Scottish Dental Practice Board were obtained. Four hundred and twenty-five
      general dental practitioners were asked to record permanent tooth extractions for
      1 week. Data requested for each extraction were: the patient's age, gender and
      dental attendance pattern, the type of tooth removed and the reason for the
      extraction. RESULTS: Three hundred and fifty-two dentists participated (a
      response rate of 82.8%). There were 25% fewer teeth extracted per patient and 30%
      fewer per dentist than in the 1984 study. In 1999, more teeth of most types were
      extracted from regular attenders whereas, in 1984, more teeth of all types were
      extracted from irregular attenders. Premolars and first and second molars were
      the tooth types most frequently extracted in both surveys. In 1999 premolars were
      the teeth most commonly removed below 21 years of age, accounting for 57.5% of
      extractions in this age range. Molars accounted for 33.8% of extractions in this
      age range compared with 52% in 1984. Overall, caries was found to be the
      principal reason for loss of all tooth types apart from lower incisors which were
      extracted mainly for periodontal reasons. However, below 21 years, 84.5% of
      premolar extractions were performed for orthodontic purposes. CONCLUSIONS: Over
      the last 15 years, the overall number of extractions has reduced and the
      proportion of extractions from regular attenders has increased. Proportionately
      more premolars and fewer molars were extracted from under-21-year-olds. This
      observation can be explained by an increase in orthodontic extractions or a
      decline in extractions for caries in this age group. However, when extractions
      from the population as a whole are considered, caries and its sequelae remains
      the principal reason for loss of all tooth types other than lower incisors which
      are extracted mainly for periodontal reasons.

PMID- 11520589
TI  - An evaluation of the acidogenic potential of maltodextrins in vivo.
AB  - Maltodextrins are a group of oligosaccharides, which are being increasingly used
      as a source of carbohydrate in many commercially available foods and drinks. This
      study investigated the effect of three different maltodextrins on the pH of
      dental plaque, in vivo, in 10 adult volunteers using the plaque harvesting
      method. The three maltodextrins tested in this study were DE=5.5, 14.0 and 18.5
      (DE=dextrose equivalents), made up as 10% solutions. Also, three commercially
      available maltodextrin containing children's drinks were evaluated for their
      acidogenicity. 10% sucrose and 10% sorbitol solutions were used as positive and
      negative controls, respectively. The minimum pH achieved for DE=5.5, 14.0 and
      18.5 was 5.83+/-0.30, 5.67+/-0.24 and 5.71+/-0.29, respectively, and were
      significantly higher as compared with that for 10% sucrose (5.33+/-0.17). The
      area under the curve was the least for DE=5.5 (12.03+/-4.64), followed by DE=18.5
      (13.13+/-8.87) and DE=14.0 (17.35+/-6.43), but were all significantly smaller as
      compared with 10% sucrose (24.50+/-8.64). The minimum pH achieved for the infant
      drinks was 6.01+/-0.24, 5.99+/-0.28 and 5.8+/-0.19 for the Lemon Barley and
      Camomile Herbal baby drink, Mixed Citrus and Hibiscus baby drink, and Infant
      Milk, respectively. It was concluded that though maltodextrins appeared to be
      significantly less acidogenic than 10% sucrose, they can lead to a substantial
      drop in plaque pH and may, therefore, have a potential to cause demineralisation
      of enamel.

PMID- 11520590
TI  - Investigation to evaluate and validate the Leeds in situ device for the study of
      enamel remineralisation in vivo.
AB  - OBJECTIVES: Recently, a novel device to generate dental plaque in situ on a
      removable human enamel surface was described. The device permitted the recovery
      of plaque intact and undisturbed on its enamel substrate. The aim of this
      investigation was to determine the utility and robustness of this model for
      analysis of the effects of therapeutics on both enamel remineralisation and on
      the overlying biofilm composition. METHODS: Enamel slices were taken from
      extracted sound human teeth, sterilised and a 'flat' area ground on each slice.
      An artificial lesion was formed within this area using acidified gel and the
      hardness of the enamel within the area of the lesion was determined at five sites
      using a 'Vickers' indenter. A nylon ring was then attached over the area of the
      lesion with cyanoacrylate and the excess enamel removed to form the completed
      device. Two devices were attached to the upper molars of 22 volunteers. Each
      volunteer was randomly assigned to receive either a fluoride containing (1500
      ppm) or a fluoride free dentifrice. The devices were retained for a 4 week period
      whilst undertaking normal oral hygiene. All procedures were conducted according
      to GCP. After a 2 week break, the volunteers were fitted with two further
      devices, given dentifrice of the alternate type and the procedure repeated.
      Plaque from each device was harvested for microbiological analyses and the enamel
      subject to microhardness measurement. Then for each device the change in
      microhardness of the enamel within the lesion over the 4 week period was
      calculated. RESULTS: There were no significant differences in viable counts of
      total aerobic bacteria, mutans streptococci or lactobacilli, nor in acidic,
      aciduric or arginolytic populations in plaque from patients using the two
      different dentifrices. However, devices subjected to the fluoride containing
      dentifrice demonstrated a significantly greater increase in microhardness of the
      enamel (P<0.025). CONCLUSIONS: These results suggest that the novel in situ
      device is capable of measuring the effect of 1500 ppm fluoride on
      remineralisation of carious enamel over a 4 week period and is also well suited
      to determining concomitant effects on plaque ecology.

PMID- 11520591
TI  - Acid resistance of human enamel in vitro after bicarbonate application during
      remineralization.
AB  - OBJECTIVES: The aim of this study was to investigate the acid resistance of
      subsurface enamel lesions remineralized with bicarbonate solutions during
      remineralization. METHODS: Two experiments were carried out. In experiment 1,
      mineral uptake and acid resistance of remineralized enamel lesions were analyzed
      quantitatively by microradiography for mineral changes. Bicarbonate solutions of
      0.5, 5.0 and 50.0 mM were used. In experiment 2, to clarify acid resistance
      mechanisms, the pH changes in demineralizing solutions on the remineralized
      enamel surfaces were measured continuously. Only a bicarbonate solution of 5.0 mM
      was used. RESULTS: In experiment 1, the bicarbonate-treated groups were more acid
      resistant than the non-treated groups (p<0.05). However, no statistically
      significant difference was observed among the different concentrations of
      bicarbonate. In experiment 2, the pH rise of the bicarbonate group was greater
      than the other groups. CONCLUSION: It was found that bicarbonate-treated enamel
      lesions were resistant to acid. It would suggest that bicarbonate ions applied
      during remineralization may have penetrated into the subsurface lesions. These
      ions may have worked as buffer agents against the acid challenge and inhibited
      the decrease in pH.

PMID- 11520592
TI  - Fracture strength and survival rate of endodontically treated maxillary incisors
      with approximal cavities after restoration with different post and core systems:
      an in-vitro study.
AB  - OBJECTIVES: This study compared the fracture strength and survival rate of
      endodontically treated crowned maxillary incisors with approximal class III
      cavities and different core build-ups. METHODS: Sixty-four caries free human
      maxillary central incisors were selected for standardized size and quality,
      endodontically treated and prepared with approximal cavities 3mm in diameter.
      Group 1 was restored with titanium posts, group 2 received zirconia posts, in
      group 3 the root canal was partially filled with a hybrid composite. In the
      control group, only the access opening was restored. All teeth were prepared for
      and restored with full cast metal alloy crowns and subsequently exposed to 1.2
      million cycles in a computer-controlled chewing simulator with simultaneous
      thermocycling. In addition, the samples were loaded until fracture in a static
      testing device. RESULTS: One specimen with composite reinforced root canal did
      not survive the dynamic load test. The following median fracture strengths in
      Newtons for the different groups were: titanium post 1038, zirconia 1057,
      composite resin 750, control (no post) 1171. The fracture load in group 3
      (composite resin) was significantly lower (P<0.05) than in the other groups.
      CONCLUSIONS: The reconstruction of endodontically treated single rooted teeth
      with approximal cavities can be successfully performed by closure of the
      endodontic and additional cavities with composite. Cementation of endodontic
      posts offers comparable but no advantageous fracture resistance. Enlargement of
      the root canal space after completion of endodontic treatment should be avoided
      and cannot be compensated for by injection of composite resin. Less catastrophic
      failures were observed without post reconstruction.

PMID- 11520593
TI  - A morphological and tensile bond strength evaluation of an unfilled adhesive with
      low-viscosity composites and a filled adhesive in one and two coats.
AB  - OBJECTIVE: The purpose of this study was to measure the tensile bond strength
      (TBS) testing of resin composite to dentin of three low-viscosity composites, in
      association with an unfilled adhesive, and a filled adhesive one and two coats
      respectively, and to evaluate and compare the SEM morphological observations.
      METHODS: The labial surface of 120 bovine lower incisors were ground to obtain a
      flat dentin surface allowing demarcation of a 4 mm diameter area with adhesive
      tape. The teeth were randomly divided in six groups of 20 each. The dentin of
      each ground surface was etched with 35% H(3)PO(4) for 15s, followed by
      application of the respective adhesive: Single Bond (SB) for Groups 1, 2, 3 and
      6; Optibond Solo (OS) for Groups 4 and 5. In Groups 1 and 4, a resin composite
      rod with a wire loop was luted directly to the adhesive surface with Z100. Group
      2 received an intermediate layer of Flow It (FI) composite; Group 3 received an
      intermediate layer of Protect Liner F (PLF) composite; Group 5 received a second
      coat of OS; and Group 6 received an intermediate layer of an experimental low
      viscosity composite (EM). A resin composite rod was luted to the surface of each
      specimen with Z100 resin composite. All specimens were stored in distilled water
      at 37 degrees C for 24h prior to TBS testing. Each specimen was inspected by SEM
      and classified according to adhesive or cohesive failure mode. One specimen of
      each group was cut longitudinally, polished and prepared for SEM observation.
      RESULTS: The TBS values were: Group 1 (7.86MPa+/-2.28), Group 2 (7.62MPa+/-1.85),
      Group 3 (7.60MPa+/-2.14), Group 4 (7.96MPa+/-2.36), Group 5 (7.50MPa+/-2.70) and
      Group 6 (7.18MPa+/-2.40). No significant statistical differences were observed
      among the groups. However, the analyses of the failure mode presented a
      considerable variation. SIGNIFICANCE: The use of a filled adhesive or an unfilled
      adhesive along with a low-viscosity composite as an intermediate layer may
      provide a stress absorbing layer, whereby improving the preservation of the
      bonded interface area.

PMID- 11520594
TI  - An evaluation of the technique sensitivity of a hydrothermal low-fusing dental
      ceramic.
AB  - OBJECTIVES: To investigate the technique sensitivity in the manipulation of
      Duceram Low-Fusing Ceramic, a hydrothermal dental veneering material by employing
      bi-axial flexure tests. METHODS: Disc shaped specimens of Duceram-LFC dentine
      powder were condensed from varying powder contents manipulated with 0.33 ml of
      liquid. Bi-axial flexure (ball-on-ring) testing was employed to determine the
      mean bi-axial flexure strength, standard deviations and Weibull modulus (m).
      Apparent solid density and apparent porosity were also measured. RESULTS: Mean bi
      axial flexure strengths and standard deviations of specimens condensed from 0.82
      g of powder were 66.47 and 9.62MPa (m=7.23, 1.32) compared with 59.12 and 13.62
      MPa (m=4.19, 0.77) and 63.91 and 14.51MPa (m=4.46, 0.81) for powder contents of
      0.78 and 0.86 g, respectively. A decrease in apparent solid density and an
      increase in apparent porosity were also associated with increasing or decreasing
      the powder content of slurry consistencies. CONCLUSIONS: A slurry consistency was
      identified for Duceram-LFC specimens where the reliability of fracture strength
      data increased. The technique sensitivity in the manipulation of Duceram-LFC
      would appear to be confirmed due to the relatively small amount of powder
      required to complete the transition from a 'fluid' to a 'thick' slurry
      consistency compared with a conventional veneering dental porcelain.

PMID- 11520595
TI  - Macrophage migration inhibitory factor in hepatocellular carcinoma and liver
      cirrhosis; relevance to pathogenesis.
AB  - The levels of macrophage migration inhibitory factor (MIF), a proinflammatory and
      carcinogenic cytokine, were significantly higher in the sera from patients with
      hepatocellular carcinoma (HCC; 25.6+/-15.3 ng/ml, n=55) and liver cirrhosis (LC;
      18.9+/-10.7 ng/ml, n=26) compared with sera from patients with gastrointestinal
      cancer (6.8+/-7.5 ng/ml, n=29) and normal controls (5.6+/-1.2 ng/ml, n=45;
      P<0.01). Hepatocytes from patients with LC and HCC, but not from chronic
      hepatitis, expressed very high levels of MIF. A possible association between
      overexpression of MIF and hepatocarcinogenesis is suggested.

PMID- 11520596
TI  - Targeting superoxide dismutase to renal proximal tubule cells inhibits
      nephrotoxicity of cisplatin and increases the survival of cancer-bearing mice.
AB  - Because cis-diamminedichloroplatinum(II) (cisplatin) which generates reactive
      oxygen species induces renal dysfunction, administration of a large dose for
      killing cancer cells is highly limited. We recently synthesized a cationic
      superoxide dismutase (SOD) (hexamethylenediamine-conjugated SOD, AH-SOD) which
      rapidly accumulates in renal proximal tubule cells and inhibits oxidative injury
      of the kidney. Treatment of Ehrlich ascites tumor cells (EATC)-bearing mice with
      cisplatin sufficient for killing tumor cells increased their motality. The
      motality of cisplatin-treated EATC-bearing mice was markedly decreased by AH-SOD.
      These results suggest that targeting SOD to renal proximal tubule cells might
      permit the administration of high doses of cisplatin and related anticancer
      agents without causing renal injury.

PMID- 11520597
TI  - Overexpression of folate binding protein alpha is one of the mechanism explaining
      the adaptation of HT29 cells to high concentration of methotrexate.
AB  - The human colon adenocarcinoma cell line HT29 can be adapted to 10(-7)- 10(-4) M
      concentrations of methotrexate (MTX). Cells adapted to 10(-4) M MTX have an
      enterocyte-like phenotype with DHFR gene amplification. Presently, we
      hypothetized that an increased expression of folate binding protein (FBP) may
      participate to the MTX resistance of 10(-4) MTX HT29 cells. The cDNA
      FBPalpha/beta-actin ratio of amplified transcripts was 4.8- and 1.5- fold higher
      in 10(-4) and in 10(-7) M MTX HT29 respectively, than in standard type HT29
      cells. An increase of transcript level was observed when decreasing folic acid
      concentration. PI-PLC cleaved 7.7 times more membrane FBP in 10(-4) M than in 10(
      7) M MTX and wild type HT29 cells. In contrast to 10(-7) M MTX cells, growth of
      10(-4) M MTX cells was dependent on folic acid concentration and abolished at a
      concentration lower than 0.9 microM. In conclusion, the adaptive mechanism of
      HT29 cells resistant to 10(-4) M MTX is the result of the synergistic
      overexpression of both DHFR and FBPalpha. Overexpression of FBPalpha may be
      related to the enterocyte-like phenotype of the cells.

PMID- 11520598
TI  - Comparison of the uptake and clearance of Tc-99m MIBI, Tl-201 and Ga-67 in drug
      resistant lymphoma cell lines.
AB  - Tc-99m sestamibi (MIBI) has been used as a tumor-seeking agent. However, its role
      in detecting lymphomas has not been widely investigated. The aim of the present
      study was to determine the uptake and clearance characteristics of Tc-99m MIBI in
      vincristine-resistant lymphoma cell lines. In addition, thallium-201 (Tl-201) and
      gallium-67 (Ga-67) uptake and clearance characteristics were evaluated for
      comparison with Tc-99m MIBI. Drug-resistant lymphoma cell lines (monocyte-like,
      histiocytic lymphoma, human; B-lymphoma cell line, American Burkitt lymphoma,
      lymphoblastoid, human; Hodgkin's disease, lymphoid, human) were selected by
      multistep vincristine treatment up to 50 nM. After incubation of the
      radiotracers, Tc-99m MIBI, Tl-201 and Ga-67, in medium for 0, 10, 20, 30, 60 or
      120 min, the uptake and clearance of each radiotracer were measured in the drug
      resistant lymphoma cell lines. In addition, P-glycoprotein expression was
      determined by immunohistochemical study. In a comparison of the three
      radiotracers, the uptake of Tc-99m MIBI was the greatest in the studied wild-type
      lymphoma cell lines. Tc-99m MIBI uptake was much lower in drug-resistant tumor
      cell lines than in non-resistant cell lines. On the other hand, the uptake
      characteristics of Tl-201 did not differ between drug-resistant and non-resistant
      cells. Immunohistochemistry analyses of Ab-1 or JSB indicated that tumor cells
      expressed MDR-1 protein in all three cell lines. Tc-99m MIBI is a good
      radiotracer for detecting drug resistance in lymphoma cell lines.

PMID- 11520599
TI  - Neuroblastoma tumor cell-binding peptides identified through random peptide phage
      display.
AB  - Random peptide phage display libraries have been employed widely to identify
      protein-protein interactions, using as targets either purified proteins, intact
      cells, or organs. To isolate peptides that bind to human neuroblastoma cells, we
      have used a phage display approach with the neuroblastoma cell line WAC 2 as the
      target. In particular, two bacteriophages, t147 and t160, displaying peptides
      p147 and p160, respectively, were isolated by repeated display cycles. Binding of
      t147 and t160 to WAC 2 cells was abrogated by pretreatment with the peptides p147
      and p160, respectively, which strongly support that cellular binding of both
      phages is dictated by their displayed peptides. Immunofluorescence analysis by
      confocal light microscopy revealed that the major proportion of t147 remains on
      the surface of WAC 2 cells and that only a fraction is taken up into the cells.
      In contrast, the vast majority of t160 is internalized. K(+) depletion reduced
      the number of the phages internalized by the cells to approximately 20% for t160
      and to 10% for t147, indicating that the phage internalization was through
      receptor-mediated endocytosis. Phage t147 appears to bind to a range of tumor
      cell lines, including neuroblastoma, breast cancer, glioblastoma and C-cell
      carcinoma, but less so to non-tumor lines, such as erythrocytes, lymphocytes,
      monocytes and epithelial cells. Phage t160 bound to a range of neuroblastoma cell
      lines and a breast cancer cell line, but not to other tested cell lines. While
      neither of the displayed peptides conferred a narrow tissue specific binding
      ability, they do provide a basis for targeted drug delivery in selected
      experimental or natural tumor systems.

PMID- 11520600
TI  - Enhanced IkappaB kinase activity is responsible for the augmented activity of NF
      kappaB in human head and neck carcinoma cells.
AB  - The nuclear transcription factor kappaB (NF-kappaB) plays an important role in
      the development and progression of cancers. However, the mechanism by which
      cancer cells in the head and neck region acquire high NF-kappaB activity has not
      yet been clarified. In this study, we examined the NF-kappaB binding activity and
      the expression of the signal-transduction-related proteins of NF-kappaB in head
      and neck carcinoma cell lines. These cancer cells showed significantly higher NF
      kappaB binding activity than normal oral epithelial and salivary gland cells. We
      also demonstrated the increased phosphorylation and degradation of IkappaB-alpha
      protein in cancer cells. Thus, enhanced NF-kappaB activity in cancer cells is
      attributable to the rapid phosphorylation and degradation of IkappaB-alpha
      protein. To further elucidate the mechanism involved in this phenomenon, we
      analyzed both the expression levels of upstream kinases (IkappaB kinase- (IKK-)
      alpha, IKK-beta, IKK-gamma, and NF-kappaB-inducing kinase (NIK)) and the IKK
      activity in cells. Although there was no significant difference in the expression
      levels of NIK, IKK-beta, or IKK-gamma in cancer cell lines compared to those in
      normal cells, increased expression of IKK-alpha protein was observed in cancer
      cells. In addition, IKK activity was significantly augmented in cancer cells as
      compared to normal cells. Thus, our results suggest that enhanced NF-kappaB
      activity in head and neck cancer cells may be due to the augmentation of IKK
      activity.

PMID- 11520601
TI  - Tumor cell differentiation by butyrate and environmental stress.
AB  - The present study shows that stress signaling plays a role in differentiation of
      K562, PANC1, HT29 and HL60 tumor cells: (1) Butyrate induced differentiation in
      K562, PANC1, and HT29 cells can be inhibited by SB203580, a specific inhibitor of
      p38 stress activated protein kinase. (2) Heat shock and hyperosmolarity increase
      expression of differentiation markers in K562, HT29, HL60 and in K562, PANC1, and
      HT29 cells, respectively. (3) Conversely, environmental stress induced
      differentiation in K562, HT29, and PANC1 cells can be inhibited by SB203580 and
      quercetin, a compound with heat shock pathway inhibiting activity. (4) Butyrate
      and environmental stress enhance either additively or synergistically
      differentiation of K562, HT29, PANC1 or HL60 cells, respectively. Stress
      signaling pathways might be an interesting pharmacologic target for
      differentiation therapy of malignant disease.

PMID- 11520602
TI  - Feature extraction and classification of breast cancer on dynamic magnetic
      resonance imaging using artificial neural network.
AB  - A neural network system was designed to extract and analyze the quantitative data
      from time-intensity profile. These data was used to predict the outcome of biopsy
      in a group of patients with histopathologically proved breast lesions. The
      performance of an artificial neural network (ANN) was compared with radiologists
      using a database with 120 patients' records each of which consisted of 14
      quantitative parameters mostly derived directly from time-intensity profile. The
      network was trained and tested using the jackknife method and its performance was
      then compared with that of the radiologists in terms of sensitivity, specificity
      and accuracy using receiver operating characteristic curve (ROC) analysis. The
      network was able to classify correctly 107 of 120 original cases and yielded a
      better diagnostic accuracy (89%), compared with that of the radiologist (79%) by
      performing a constructive association between extracted quantitative data and
      corresponding pathological results (r=0.72, P<0.001).

PMID- 11520603
TI  - Reinitiated expression of EJras transgene in targeted epidermal cells of
      transgenic rabbits by cottontail rabbit papillomavirus infection.
AB  - Transgenic rabbits carrying the EJras oncogene have been established in our
      laboratory (Am. J. Pathol. 155 (1999) 315). The expression of the ras gene is
      targeted to the epidermal keratinocytes using the upstream regulatory region
      (URR) of the cottontail rabbit papillomavirus (CRPV). All of the transgenic
      rabbits develop keratoacanthomas at multiple sites in the skin at 2-3 days after
      birth, and the tumors spontaneously regress in 1.5-2 months. With regression of
      the keratoacanthomas, the rabbits appear normal and EJras expression is
      undetectable in their skin. To determine if CRPV infection would reinitiate the
      expression of the EJras transgene and make the rabbits more sensitive to
      tumorigenesis, the rabbits were infected with CRPV at 2 months of age when the
      keratoacanthomas had regressed. This study shows that CRPV infection of the
      transgenic rabbit skin could shorten the latency required for CRPV papilloma
      initiation, and significantly increase the tumor growth and persistence rate
      compared with non-transgenic rabbits. Furthermore, EJras expression became
      detectable in the CRPV induced papillomas in transgenic rabbits, but not in the
      papillomas of non-transgenic rabbits. These results indicate that CRPV infection
      is able to reinitiate the expression of the CRPV URR controlled EJras oncogene
      carried by the transgenic rabbits and that the expression of EJras can enhance
      the tumorigenesis of CRPV infection.

PMID- 11520604
TI  - Human prostate cancer cells adhere specifically to hemoglobin: a possible role in
      bone-specific metastasis.
AB  - From the supernatant of rabbit bone marrow, we isolated an organ-specific factor,
      which was related with the metastasis of prostate cancer to the bone and examined
      its adhesion to prostate cancer cells (PC-3). Molecular weight and amino acid
      sequence analyses of the active component obtained by high performance liquid
      chromatography revealed that a component identical to the alpha chain of
      hemoglobin accounted for 80% of the biological activity. Hemoglobin showed over
      50% adhesion to PC-3 cells but only 10% adhesion to human colon cancer cell
      lines, representative of organ non-specific metastasis, and leukemia cells line,
      representative of a non-solid tumor. Some substance in the bone marrow may
      promote the first step of adhesion of cancer cells to bone marrow in the
      metastasis of prostate cancer to the bone, possibly an amino acid sequence or
      some tertiary structure similar to hemoglobin.

PMID- 11520605
TI  - Loss of MHC class II inducibility in hyperplastic tissue in Rb-defective mice.
AB  - Retinoblastoma gene (Rb) defects occur frequently in human tumors. Studies of Rb
      defective human tumor cell lines and Rb-/- murine embryonic fibroblasts
      demonstrate that Rb is required for interferon-gamma (IFN-gamma) induced major
      histocompatibility complex (MHC) class II expression. MHC class II expressing
      tumors generate anti-tumor immune responses associated with tumor-specific
      infiltrating lymphocytes. The role of Rb in IFN-gamma induced MHC class II
      expression on an endogenous tumor was examined by immunohistochemical staining
      for IAbeta and Rb on tissues from Rb+/- mice. MHC class II IAbeta is not induced
      by IFN-gamma in Rb-deficient neoplastic cells, but remains inducible in related
      normal tissue.

PMID- 11520606
TI  - Differential osteopontin expression in lung cancer.
AB  - Osteopontin (OPN) is a phosphorylated glycoprotein with diverse functions
      including cancer development, progression and metastasis. Its expression is
      induced by a variety of stimuli such as TNF-alpha and Ras proto-oncogene.
      However, differential OPN expression and its regulation in each histologic type
      of lung cancer are not well established. In this study, we assessed expression of
      OPN in lung cancer tissues with immunohistochemical analysis. OPN was
      predominantly expressed in tumor cells of non-small cell lung cancer (NSCLC)
      tissues: 11 of 16 cases (68.8%) of squamous cell carcinoma (SCC), five of 24
      cases (20.8%) of adenocarcinoma (AD), but only two of 18 cases (11%) of small
      cell lung cancer (SCLC). Expectedly, OPN was principally expressed in NSCLC cell
      lines (H322 cells and HL460 cells) but not in SCLC cell line (H69 cells) by
      Western blotting and Northern blotting. Interestingly, Ras-p21 was specifically
      co-expressed with OPN staining in eight of eight cases with SCC (100%), whereas
      it was demonstrated in three of ten cases (30%) with AD and only one of 18 cases
      (5%) with SCLC. Collectively, these results suggest that OPN is mainly expressed
      in NSCLC, especially among SCC. OPN expression may be tightly regulated by Ras
      oncogene, and its concomitant induction with Ras activation may play a crucial
      role in the development of SCC.

PMID- 11520607
TI  - Hepatitis C virus core protein: intriguing properties and functional relevance.
AB  - Hepatitis C virus (HCV) often causes a prolonged and persistent infection, and an
      association between hepatocellular carcinoma (HCC) and HCV infection has been
      noted. The pathogenesis of liver damage is at least in part related to virus
      mediated factors. Understanding the molecular basis of pathogenesis is a major
      challenge in gaining insight into HCV-associated disease progression. Recent
      experimental evidence using HCV cloned genomic regions suggests that the core
      protein has numerous functional activities. These include its likely role in
      encapsidation of viral RNA, a regulatory effect on cellular and unrelated viral
      promoters, interactions with a number of cellular proteins, an modulatory role in
      programmed cell death or apoptosis under certain conditions, involvement in cell
      growth promotion and immortalization, induction of HCC in transgenic mice, and a
      possible immunoregulatory role. These intriguing properties suggest that the core
      protein, in concert with cellular factors, may contribute to pathogenesis during
      persistent HCV infection.

PMID- 11520608
TI  - Bacterial flagella and type III secretion systems.
AB  - Certain classes of pathogenic bacteria secrete virulence proteins in a Sec
      independent manner, by a mechanism known as type III secretion. The main body of
      the export apparatus specific for virulence proteins is identified as a needle
      complex, which has a similar structural organization to flagella. The two
      structures share several proteins with highly homologous amino acid sequences.
      Even where the sequence identity is low among flagellar proteins from various
      species, the physico-chemical properties of each protein remain homologous.
      Therefore, by comparing the physico-chemical properties of unidentified proteins,
      it is possible to find homologs among type III secretion systems.

PMID- 11520609
TI  - The effect of culture conditions on the mycelial growth and luminescence of
      naturally bioluminescent fungi.
AB  - The effects of temperature, light and pH on mycelial growth and luminescence of
      four naturally bioluminescent fungi were investigated. Cultures of Armillaria
      mellea, Mycena citricolor, Omphalotus olearius and Panellus stipticus were grown
      at 5 degrees C, 15 degrees C, 22 degrees C and 30 degrees C, under 24 h light, 12
      h light/12 h dark and 24 h dark, and at a pH ranging from 3.5 to 7 in three
      separate experiments. Temperature and pH had a significant effect on mycelial
      growth and bioluminescence, however light did not. Bioluminescence and mycelial
      growth were optimum at 22 degrees C and pH 3-3.5, the exception being M.
      citricolor for which bioluminescence and growth were optimum at pH 5-6 and pH 4,
      respectively. With the exception of M. citricolor, bioluminescence and mycelial
      growth were greater under 24 h darkness. An understanding of the effect of
      culture conditions on mycelial growth and luminescence is necessary for the
      future application of bioluminescent fungi as biosensors.

PMID- 11520610
TI  - Different in vivo localization of the Escherichia coli proteins CspD and CspA.
AB  - Two Csp proteins (CspA and CspD) were fused to the green fluorescent protein GFP
      and expressed from their natural promoters or from an inducible promoter.
      Fluorescence microscopy and computerized image analysis indicate that in
      Escherichia coli growing at 37 degrees C CspD localizes in the nucleoid like the
      control H-NS while CspA occupies a polar position away from the nucleoid.
      Following cold shock CspA maintains its location, while CspD is not sufficiently
      expressed to permit its localization. The different localization of CspA and CspD
      indicates that these proteins play different roles in the cell in spite of their
      extensive structural similarity.

PMID- 11520611
TI  - Glutamine synthetase from Acetobacter diazotrophicus: properties and regulation.
AB  - Glutamine synthetase from Acetobacter diazotrophicus, an endophyte originally
      isolated from sugarcane, was studied as a step in the identification of
      mechanisms underlying the role of A. diazotrophicus as a major supplier of fixed
      nitrogen to its host plant. The enzyme was purified and partially characterized.
      It was also shown that the enzyme is regulated by adenylylation in response to
      the nitrogen source. Interestingly, there is no upregulation of the synthesis of
      the enzyme under diazotrophic conditions, which is in contrast to the situation
      in enterics, e.g. Klebsiella pneumoniae.

PMID- 11520612
TI  - The sites of interaction of triphenyltetrazolium chloride with mitochondrial
      respiratory chains.
AB  - The inability of cells and microorganisms to reduce the colourless electron
      acceptor triphenyltetrazolium chloride (TTC) to a red formazan precipitate is
      commonly used as a means of screening for cells that have a dysfunctional
      respiratory chain. The site of reduction of TTC is often stated to be at the
      level of cytochrome c oxidase where it is assumed to compete with oxygen for
      reducing equivalents. However, we show here that TTC is reduced not by cytochrome
      c oxidase but instead by dehydrogenases, particularly complex I, probably by
      accepting electrons directly from low potential cofactors. The reduction rate is
      fastest in coupled membranes because of accumulation in the matrix of the
      positively charged TTC+ cation. However, the initial product of TTC reduction is
      rapidly reoxidised by molecular oxygen, so that generation of the stable red
      formazan product from this intermediate occurs only under strictly anaerobic
      conditions. Colonies of mutants defective in cytochrome oxidase do not generate
      sufficiently anaerobic conditions to allow the intermediate to form the stable
      red formazan. This revision of the mode of interaction of TTC with respiratory
      chains has implications for the types of respiratory-defective mutants that might
      be detected by TTC screening.

PMID- 11520613
TI  - BceS1, a new addition to the type III restriction and modification family.
AB  - The nucleotide sequence of an 11-kb chromosomal BglII fragment from Bacillus
      cereus American Type Culture Collection (ATCC) 10987 strain revealed two closely
      adjacent open reading frames organized in an operon, of which the deduced amino
      acids showed identity to the type III restriction and modification (R/M) subunits
      described in Gram-negative bacteria. An enhanced transcription level was revealed
      when the culture was grown in the presence of foreign DNA. A cell-free extract
      from this culture restricted pUC19, whereas from a plain medium the restriction
      was very weak. The in vitro methylation protected pUC 19 from restriction. The
      R/M system was designated BceS1 as this endonuclease required ATP and Mg2+ as
      cofactors like other type III endonucleases. BceS1 is the first chromosomal type
      III R/M system characterized in a Gram-positive bacterium.

PMID- 11520614
TI  - Identification of the green alga, Chlorella vulgaris (SDC1) using cyanobacteria
      derived 16S rDNA primers: targeting the chloroplast.
AB  - We have tested a set of oligonucleotide primers originally developed for the
      specific amplification of 16S rRNA gene segments from cyanobacteria, in order to
      determine their versatility as an identification tool for phototrophic
      eucaryotes. Using web-based bioinformatics tools we determined that these primers
      not only targeted cyanobacterium sequences as previously described, but also 87%
      of sequences derived from phototrophic eucaryotes. In order to qualify our
      finding, a type culture and environmental strain from the freshwater unicellular,
      green algae genus Chlorella Beijerinck, were selected for further study.
      Subsequently, we sequenced a 578-bp fragment of the 16S rRNA gene, which proved
      to be present within the chloroplast genome, performed sequence analysis and
      positively identified our solvent-degrading environmental strain (SDC1) as
      Chlorella vulgaris.

PMID- 11520615
TI  - Distribution of papG alleles among uropathogenic Escherichia coli isolated from
      different species.
AB  - The distribution of alleles I, II and III of the P adhesin gene papG among
      Escherichia coli isolated from urinary tract infections in humans, dogs and cats
      was studied by PCR. Allele I was present in 6% and 5% of the human and cat
      isolates. Allele II as such was present in 30% and 22%, or in association with
      allele III in 12% and 2% of the human and canine isolates, respectively. Allele
      III was present in 33% of the human strains and predominated largely over allele
      II in E. coli isolates from cystitis of animal origin (72% in dog and 95% in cat
      strains). The three different classes of the PapG adhesin have been suggested to
      play a role in host specificity, for example human versus canine specificity.
      Recent studies, however, showed papG III positive human and dog cystitis isolates
      to be largely indistinguishable. We found the Class II allele in animal isolates
      and detected for the first time in Europe the Class I allele in a different
      genetic background than the J96-like clonal group. Our findings show that
      uropathogenic E. coli isolates from different species can have the same papG
      alleles and thus may have zoonotic potential.

PMID- 11520616
TI  - Polymerase chain reaction assay for the detection of Bacillus cereus group cells.
AB  - Recent investigations have shown that members of the Bacillus cereus group carry
      genes which have the potential to cause gastrointestinal and somatic diseases.
      Although most cases of diseases caused by the B. cereus group bacteria are
      relatively mild, it is desirable to be able to detect members of the B. cereus
      group in food and in the environment. Using 16S rDNA as target, a PCR assay for
      the detection of B. cereus group cells has been developed. Primers specific for
      the 16S rDNA of the B. cereus group bacteria were selected and used in
      combination with consensus primers for 16S rDNA as internal PCR procedure
      control. The PCR procedure was optimized with respect to annealing temperature.
      When DNA from the B. cereus group bacteria was present, the PCR assay yielded a
      B. cereus specific fragment, while when non-B. cereus prokaryotic DNA was
      present, the consensus 16S rDNA primers directed synthesis of the PCR products.
      The PCR analyses with DNA from a number of non-B. cereus confirmed the
      specificity of the PCR assay.

PMID- 11520617
TI  - The shxVW locus is essential for oxidation of inorganic sulfur and molecular
      hydrogen by Paracoccus pantotrophus GB17: a novel function for lithotrophy.
AB  - The shxVW genes of Paracoccus pantotrophus were identified to be essential for
      lithotrophic oxidation of sulfur and hydrogen. shxV predicts a membrane protein
      which is 42% identical to CcdA of P. pantotrophus essential for cytochrome c
      biogenesis. shxW predicts a periplasmic thioredoxin. Disruption of shxV by an
      Omega-kanamycin interposon disabled the resulting mutant GB(Omega)V to grow with
      thiosulfate or molecular hydrogen and to express ShxW while cytochrome c
      formation was not affected. Mixotrophic growth with succinate and thiosulfate of
      strain GB(Omega)V revealed 2% of the thiosulfate-dependent oxygen uptake rate as
      compared to the wild-type while antigens of proteins essential for sulfur
      oxidation were present in both strains. Mixotrophic growth of strain GB(Omega)V
      with succinate and molecular hydrogen revealed neither hydrogenase activity nor
      antigens. Complementation analysis with plasmid pBHP6 carrying the shxVW genes
      revealed the wild-type phenotype of strain GB(Omega)V(pBHP6).

PMID- 11520618
TI  - Synthesis of six novel N,N-dialkyl derivatives of spermidine and effects on
      growth of the fungal plant pathogen Pyrenophora avenae.
AB  - Six novel N,N-dialkyl derivatives of spermidine were synthesised and examined for
      activity against the oat stripe pathogen Pyrenophora avenae. Two of these
      spermidine analogues, N,N-dimethyl-N1-(3-aminopropyl)-1,3-diaminopropane
      trihydrochloride (27) and N,N-dimethyl-N1-(3-aminopropyl)-1,4-diaminobutane
      trihydrochloride (28), reduced radial extension of P. avenae on plates when used
      at 2 mM, and caused more substantial reductions in fungal growth in liquid
      culture when used at 1 mM. Preliminary data suggest that neither compound
      affected polyamine biosynthesis, determined by following the incorporation of
      label from ornithine into polyamines and examining intracellular polyamine
      concentrations in fungal tissue.

PMID- 11520619
TI  - Characterisation of the yeast Pichia membranifaciens and its possible use in the
      biological control of Botrytis cinerea, causing the grey mould disease of
      grapevine.
AB  - Pichia membranifaciens strain FY-101, isolated from grape skins, was found to be
      antagonistic to Botrytis cinerea, the causal organism of the grey mould disease
      of the grapevine. When grown together on solid as well as liquid media, the yeast
      brings about the inhibition of this parasitic fungus, coagulation and leakage of
      its cytoplasm, and suppression of its ability to produce the characteristic grey
      mould symptoms on the grapevine plantlets. In vitro experiments confirm that this
      yeast can be used as a biological control organism against B. cinerea. An account
      of the molecular characterisation of P. membranifaciens (complete sequence of the
      ITS region of its ribosomal DNA, GenBank accession No. AF 270935), as well as the
      interaction between B. cinerea and the yeast, are given here.

PMID- 11520620
TI  - Identification of a secreted superoxide dismutase in Mycobacterium avium ssp.
      paratuberculosis.
AB  - Mycobacterium avium ssp. paratuberculosis (M. paratuberculosis), the causative
      agent of Johne's disease, is an important animal pathogen that has also been
      implicated in human disease. The major proteins expressed by M. paratuberculosis
      were analyzed by two-dimensional gel electrophoresis, and a superoxide dismutase
      (Sod) was identified from this protein profile. The M. paratuberculosis Sod has a
      molecular mass of 23 kDa and an isoelectric point of 6.1. Sequence analysis of
      the corresponding sodA gene from M. paratuberculosis indicates that this protein
      is a manganese-dependent enzyme. We show that the M. paratuberculosis Sod is
      actively secreted, suggesting that it may elicit a protective cellular immune
      response in the host during infection.

PMID- 11520621
TI  - ITS region of the rDNA of Pythium longandrum, a new species; its taxonomy and its
      comparison with related species.
AB  - Pythium longandrum (F-73.0) was isolated, from soil samples taken in Lille in
      northern France. Morphologically the fungus resembles closely Pythium rostratum,
      however its antheridial characters are unique. The oogonia of this species are
      provided with hypogynous and monoclinous antheridia. The antheridial cells are
      inflated and are probably the largest and longest for the genus. The internal
      transcribed spacer region of its nuclear ribosomal DNA indicates that it is
      entirely different from all other species of Pythium. This new species is
      characterized by its spherical to elongated sporangia, smooth-walled oogonia and
      hypogynous to monoclinous antheridia bearing long antheridial cells closely
      applied to the oogonia. Morphological features of this new species, together with
      the sequences of the ITS region of its nuclear ribosomal DNA and comparison with
      related species are discussed here.

PMID- 11520622
TI  - Novel sigmaF-dependent genes of Escherichia coli found using a specified promoter
      consensus.
AB  - Availability of whole genome information opens new bioinformatics approaches to
      study global regulation. We developed a program, named ScanProm, that allows to
      search a genome database for promoter consensus elements. The program uses a
      multiple alignment of previously identified components of a regulon as an input
      and generates a consensus profile. The profile is then optimized by adjusting the
      cutoff value for position-specific similarity assessment and used for a genome
      scan to search for unknown members of the regulon. The candidates obtained are
      scored by their similarity to the consensus profile. The ScanProm program was
      applied to search for novel members of the class III flagellar regulon of
      Escherichia coli. The search template included the previously defined 4 bp (-35)
      and 8 bp (-10) promoter elements, presumably recognized by the flagellar-specific
      sigmaF, with additional 4 bp at the 3' of the -35 consensus. The majority of
      highly scoring candidates obtained from the whole genome sequence scan were known
      class III genes, although several new genes were also identified. We tested 10
      novel highly scoring candidate class III genes by cloning their promoter
      fragments into a fusion vector designed to monitor the transcriptional activity
      with lacZ. Two of these genes, b2737(ygbK) and ppdAB, were found to be dependent
      on FlhDC, the master regulator of the flagellar genes. The regulation of these
      genes by sigmaF was further confirmed by comparing their expression in the wild
      type and fliA backgrounds. An overproduction or inactivation of these genes did
      not exhibit any notable phenotypes in motility or chemotaxis.

PMID- 11520623
TI  - Two new loci affecting cell division identified as suppressors of an ftsQ-null
      mutation in Streptomyces coelicolor A3(2).
AB  - Mutations in fts genes partially or completely block both vegetative cell
      division and sporulation septation in the filamentous bacterium Streptomyces
      coelicolor A3(2). Using a novel screen, we independently isolated two double
      mutant strains, each containing a spontaneous suppressor mutation, which
      partially restores division to an ftsQ-null mutant. Genetic complementation
      experiments revealed that the suppressor mutations alone confer no observable
      defect in sporulation. The suppressor mutations were genetically mapped to
      regions of the chromosome, distinct from each other and the division and cell
      wall cluster containing ftsQ. Therefore, the genes identified by the suppressor
      mutations were named sqnA and sqnB (suppressor of ftsQ-null) and may be
      representatives of a novel class of genes involved in cell division or the
      regulation of cell division in this mycelial organism.

PMID- 11520624
TI  - Immunoreactive epidermal growth factor receptors are present in gastrointestinal
      epithelial cells of preterm infants with necrotising enterocolitis.
AB  - INTRODUCTION: Epidermal growth factor (EGF) affects epithelial cell
      proliferation, differentiation and migration in the gastrointestinal tract of
      experimental animals, and increases proliferation when given intravenously to
      children with congenital microvillous atrophy or necrotising enteritis. The aim
      of the present study is to determine whether EGF receptors (EGFR) are present in
      the gut epithelium of preterm infants, and to discover whether neonatal
      necrotising enterocolitis (NEC) is associated with the absence of EGFR from
      mucosal cells. METHODS: Tissues were taken from involved colon and small
      intestine of four preterm infants with NEC, and control tissues were taken from
      four other neonates who had laparatomies for congenital malformations. Sections
      of the tissues were examined histopathologically after treatment with a
      monoclonal antibody against the external domain of the EGFR (Zymed Laboratories,
      San Francisco, CA, USA). RESULTS: Histopathological examination confirmed
      diagnosis of NEC in the involved bowel and controls showed appearance within
      normal limit. Immunoreactive EGFR were present on the epithelial cells of both
      the colon and small intestine, localised on the basolateral membrane of the cells
      of both subject and the controls. There was no apparent reduction in expression
      compared with controls. CONCLUSION: NEC in preterm infants is not associated with
      absence of EGFR. The presence of EGFR in gut epithelial cells raises the
      possibility of using EGF for prophylaxis or treatment of NEC.

PMID- 11520625
TI  - The characterization of superoxide production of human neonatal neutrophil.
AB  - To assess the role of neutrophil in neonatal host defense against microbial
      infection, we characterized the superoxide anion (O(2-)) production of neonatal
      neutrophil on a biochemical basis. After taking an appropriate informed consent,
      neutrophils were obtained from cord blood immediately after transvaginal delivery
      and divided into two groups: the Preterm group, 15 neonates (27-36 weeks'
      gestation) and the Term group, 15 neonates (37-41 weeks' gestation). Eleven
      healthy adults served as controls in the Adult group. The value of N-formyl
      methionyl-leucyl-phenylalanin (fMLP)-induced O(2-) production activity of
      neutrophils in the Preterm group using chemiluminescence assay was significantly
      lower than those values in both the Term and Adult groups (5.77+/-0.53x10(6) vs.
      11.1+/-0.94x10(6) and 10.7+/-0.63x10(6) cpm; mean+/-S.E.M., p<0.05). In phorbol
      12-myristate 13-acetate (PMA)-stimulation, the values of O(2-) production
      activity of neutrophils in both the Preterm and Term groups were significantly
      lower than that in the Adult group (13.0+/-1.66x10(6) and 18.0+/-1.44x10(6) vs.
      27.3+/-1.45x10(6) cpm, p<0.05). Scatchard analysis of [(3)H]fMLP binding to
      neutrophil demonstrated a two-receptor model in each group, and the number of
      high-affinity receptors per neutrophil in the Preterm group was significantly
      lower than those in other groups (p<0.05). However, cord blood levels of
      proinflammatory cytokines, such as interleukin (IL)-6, -8, and tumor necrosis
      factor-alpha (TNF-alpha) did not differ in either neonatal group. These results
      indicated that the fMLP-induced O(2-)production activity of neutrophils in the
      term neonates was enhanced at the level of the receptor and suggested that this
      enhanced production contribute to the neonatal host defense against microbial
      infection.

PMID- 11520626
TI  - Neurotransmitters and neuromodulators during early human development.
AB  - BACKGROUND: Neurotransmitters such as monoamines appear in the embryo before the
      neurones are differentiated. They may have other functions than neurotransmission
      during embryogenesis such as differentiation and neuronal growth. For example,
      serotonin may act as a morphogen. A number of neuropeptides are expressed during
      ontogenesis, but their function has been difficult to establish. Maybe some of
      them remain as evolutionary residues. Fast-switching neurotransmitters like the
      excitatory amino acids and the more ionotropic receptors dominate in the human
      brain, but appear probably later during evolution as well as during ontogeny.
      METHODS: The distribution of catecholamines during development has been analysed
      with a fluorescence method, while most of the other neurotransmitters have been
      mapped with immunohistochemical methods. The classical method to determine the
      physiological role of a neurotransmitter or modulator is to study the
      physiological effect of its antagonist, blocking the endogenous activity. By
      transgenic technique, the genes encoding for enzymes involved in the synthesis of
      neurotransmitters can be knocked-out. MAJOR FINDINGS: Pharmacological blocking of
      endogenous activity has, for example, demonstrated that adenosine suppresses
      fetal respiration. Knocking out the dopamine beta-hydroxylase gene results in
      fetal death, suggesting that noradrenaline is essential for survival. Some
      neurotransmitters change their effect during embryogenesis, e.g. GABA which is
      excitatory in the embryo, but inhibitory after birth due to a switch from a high
      to low chloride content in the nerve cells. It is possible that this is of
      importance for the wiring of neuronal network in early life. NMDA receptors
      dominate in the foetus, while kainate and AMPA receptors appear later. At birth,
      there is a surge of neurotransmitters such as catecholamines, which may be of
      importance for the neonatal adaptation. CONCLUSIONS: Neurotransmitters and
      modulators are not only important for the neural trafficking in the embryo, but
      also for the development of the neuronal circuits. Prenatal or neonatal stress
      (hypoxia), as well as various drugs, may disturb the wiring and cause long-term
      behavioural effects (fetal and neonatal programming).

PMID- 11520627
TI  - Home oxygen therapy in infants with bronchopulmonary dysplasia: assessment of
      parental anxiety.
AB  - BACKGROUND: It is conceivable that a complicated recovery course in a high-risk
      premature infant managed at home generates apprehension and anxiety in parents.
      AIMS: We attempted to define the evolution of anxiety levels in a population of
      parents of low-birth-weight premature infants with bronchopulmonary dysplasia
      enrolled in a prospective home O(2) therapy program. STUDY DESIGN: In the
      immediate pre-discharge [mean postnatal age 95 (45-158) days], a questionnaire
      (State-Trait Anxiety Inventory form Y) was given to all parents of the premature
      infants [mean birth weight 1106 (0.610-1.770) kg; mean gestational age 27.1 (24
      31) weeks] present for the discharge. Subsequently, the parents were assessed
      twice, initially after a week from the discharge of their infants and then at the
      end of the oxygen therapy phase [mean postnatal age 185 (60-361) days]. They
      included 10 mothers and 10 fathers, aged 33.5+/-0.5 and 37+/-0.2 years,
      respectively. RESULTS: Our results indicate that these parents present an
      increased state anxiety level upon hospital discharge of their oxygen-dependent
      premature infants, which decreases as the improvement of respiratory status and
      the cessation of oxygen-dependency become evident [mean+/-S.D. related to age (T)
      maternal values 47.1+/-7.0, 41.8+/-5.6, 39.1+/-4.7, respectively; mean+/-S.D.
      related to age (T) paternal values 42.2+/-8.5, 41.1+/-8.1, 40.5+/-8.2,
      respectively]. When assessed separately by parental gender, in the maternal
      group, state anxiety decreased significantly (ANOVA, p<0.05). CONCLUSIONS: These
      data indicate that although neonatologists generally define the discharge of
      prematures with chronic lung disease based upon the acquired stabilization of
      vital parameters, in the oxygen-dependent group, they should also pay special
      attention to the emotional support of the parents who we have identified as being
      at increased risk for pre-discharge anxiety.

PMID- 11520628
TI  - Doppler velocimetry in the adrenal artery in human fetuses.
AB  - BACKGROUND: Fetal hypoxia and/or acidosis causes redistribution of blood flow to
      the high-priority organs including the adrenal glands. Although this phenomenon
      is well described in the human cerebral and placental circulations using Doppler
      velocimetry, there are few reports about the adrenal glands. AIM: To clarify the
      gestational age-related changes in adrenal blood flow in normal fetuses and
      fetuses at risk of hemodynamic derangement. MATERIAL AND METHODS: In 153 normal
      cases, the resistance indices (RIs) calculated from the blood flow velocity
      waveforms (FVWs) in the middle adrenal artery (MAA) were obtained from 24 weeks
      to construct nomogram using regression analysis. Twenty-seven complicated cases
      were divided according to the 5%ile RI values in the MAA, and clinical outcomes
      were retrospectively compared. RESULT: The RI values in the MAA increased until
      31 weeks and decreased thereafter. The 50%ile regression curve was represented as
      RI=-0.000914 (weeks)(2)+0.0579 weeks-0.181. Of the 27 complicated cases, 13 had
      RIs in the MAA below the 5%ile. Cases with low RI had significantly higher RI
      ratio in regard of UA/MCA; higher occurrence of abnormal FHR patterns on
      observation; higher incidence of cesarean delivery for nonreassuring fetal well
      being status; earlier gestational age at delivery; lower birth weights and longer
      periods of admission to NICU than the cases with normal RI. CONCLUSION: We have
      described the nomogram for the RI in the MAA. In conditions of fetal hypoxia or
      acidemia, blood flow redistribution to the adrenal glands may occur and the
      analysis of the adrenal artery FVWs may be useful in detection of fetal altered
      hemodynamics.

PMID- 11520629
TI  - Fetal aortic blood flow assessment from the relationship between fetal aortic
      diameter pulse and flow velocity waveforms during fetal development.
AB  - BACKGROUND: Blood flow is calculated from mean velocity across the vessel and its
      cross-sectional area and is related to the fetal growth. AIM: To investigate the
      relationship between diameter pulse waveform (DPW) and flow velocity waveform
      (FVW) in the fetal descending aorta during fetal development. STUDY DESIGN:
      Doppler ultrasound and a phase-locked loop echo tracking system were used to
      measure the FVW and DPW in the fetal descending aorta, respectively. SUBJECTS: We
      studied 137 normal-growth fetuses (normal group, 20-40 weeks) and 51 fetuses with
      high umbilical artery pulsatility index (umbilical placental insufficiency, UPI
      group, 26-40 weeks). OUTCOME MEASURES: We measured the systolic (Sd), diastolic
      (Dd) diameters, time diameter integral (TDI) and time velocity integral (TVI) and
      then calculated the TVI x TDI and TVI to TDI ratio. RESULTS: Normal fetal growth
      was associated with an increase in Sd, Dd, pulse amplitude, TVI, TDI and TVI x
      TDI. The FVW began to resemble the DPW with decreasing downstream resistance
      produced by growth of the placenta. The TVI was increased relative to the TDI.
      The differences in Sd, Dd, TDI and TVI x TDI between the normal and UPI groups
      were not significant. The TVI was decreased relative to the TDI. There was a
      decrease in the TVI as a ratio of the TDI. The Dd per unit fetal weight was high
      in the compromised fetuses. Fetal outcome was examined in relation to the TVI to
      TDI ratio. Those with a low ratio (below 10th centile) exhibited significantly
      more adverse indices of fetal outcome. CONCLUSIONS: In fetal compromise there is
      an increase in diastolic pressure in association with high placental resistance,
      which causes a major increase in afterload. The efficient circulation associated
      with fetal growth might be represented by an increase in the ratio of the TVI to
      the TDI (an index of efficient circulation) when these waveform shapes resemble
      each other.

PMID- 11520630
TI  - The effect of monaural middle ear destruction on postnatal development of
      auditory response properties of mouse inferior collicular neurons.
AB  - This study examined the effect of monaural middle ear destruction on postnatal
      development of auditory response properties of inferior collicular (IC) neurons
      of the laboratory mouse, Mus musculus. Monaural middle ear destruction was
      performed on juvenile and adult mice and the auditory response properties of
      neurons in both ICs were examined 4 weeks thereafter. IC neurons of control mice
      typically had lower minimum thresholds, larger dynamic ranges and greater Q(10)
      values than IC neurons of experimental juvenile and adult mice. In experimental
      mice, neurons in the ipsilateral IC (relative to the intact ear) typically had
      longer latencies, higher minimum thresholds, and smaller dynamic ranges than
      neurons in the contralateral IC. In experimental adult mice, neurons in the
      ipsilateral IC had sharper frequency tuning curves than neurons in the
      contralateral IC. Clear tonotopic organization was only observed in the IC of
      control mice and experimental adult mice. However, the correlation of increasing
      minimum threshold with best frequency was observed for IC neurons in control mice
      but not in experimental juvenile and adult mice. Possible mechanisms for these
      different response properties are discussed.

PMID- 11520631
TI  - Carboplatin-induced oxidative stress in rat cochlea.
AB  - Carboplatin is currently being used in the clinic against a variety of human
      cancers. However, high dose carboplatin chemotherapy resulted in ototoxicity in
      cancer patients. This is the first study to show carboplatin-induced oxidative
      stress response in the cochlea of rat. Male Wistar rats were divided into two
      groups of six animals each and treated as follows: (1) control (normal saline,
      i.p.) and (2) carboplatin (256 mg/kg, i.p.). Animals in both groups were sedated
      with ketamine/xylazine and auditory brainstem-evoked responses were recorded
      before and 4 days after treatments. The animals were sacrificed on the fourth day
      and cochleae were harvested and analyzed. A significant elevation of the hearing
      threshold shifts was noted at clicks, 8, 16, and 32 kHz tone burst stimuli
      following carboplatin administration. Carboplatin significantly increased nitric
      oxide and malondialdehyde levels, xanthine oxidase and manganese-superoxide
      dismutase activities in the cochlea indicating enhanced flux of free radicals.
      Cochlear glutathione levels, antioxidant enzyme activities such as copper zinc
      superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and
      glutathione S-transferase and enzyme protein levels were significantly depleted 4
      days after carboplatin treatment. The data suggest that carboplatin induced free
      radical generation and antioxidant depletion, and caused oxidative injury in the
      cochleae of rats.

PMID- 11520632
TI  - Does exogenous GM1 ganglioside enhance the effects of electrical stimulation in
      ameliorating degeneration after neonatal deafness?
AB  - This study examined the combined effects of administration of exogenous GM1
      ganglioside and electrical stimulation on the cochlear nucleus (CN) of cats
      deafened neonatally by ototoxic drugs. Five normal hearing adult cats served as
      controls. Another 12 cats were deafened bilaterally by daily injections of
      neomycin sulfate (60 mg/kg) for 17-21 days after birth until auditory brainstem
      testing demonstrated profound hearing loss. Six of the deaf animals comprised the
      GM1 group, which received daily injections of GM1 ganglioside (30 mg/kg) for 28
      38 days during the period after profound deafness was confirmed, and prior to
      receiving a cochlear implant. The non-GM1 group (n=6) received no treatment
      during this interim period. All the deafened animals underwent unilateral
      cochlear implantation at 6-9 weeks postnatal and received several months (mean
      duration, 32 weeks) of chronic electrical stimulation (4 h/day, 5 days/week).
      Stimulation was delivered by intracochlear bipolar electrodes, using electrical
      signals that were designed to be temporally challenging to the central auditory
      system. Results showed that in the neonatally deafened animals, both the GM1 and
      non-GM1 groups, the volume of the CN was markedly reduced (to 76% of normal), but
      there was no difference between the animals that received GM1 and those that did
      not. The cross sectional areas of spherical cell somata in both GM1 and non-GM1
      groups also showed a highly significant reduction in size, to < or =75% of normal
      after neonatal deafening. Moreover, in both the GM1 and non-GM1 groups, the
      spherical cells in the CN ipsilateral to the implanted cochlea were significantly
      larger (6%) than cells in the control, unstimulated CN. Again, however, there was
      no significant difference between the GM1 group and the non-GM1 group in
      spherical cell size. These results contrast sharply with previous reports that
      exogenous GM1 prevents CN degeneration after neonatal conductive hearing loss and
      partially prevents spiral ganglion cell degeneration when administered
      immediately after ototoxic drug deafening in adult animals. Taken together,
      findings to date suggest that GM1 may be effective in preventing degeneration
      only if the GM1 is administered immediately at the time hearing loss occurs.

PMID- 11520633
TI  - The responses of single units in the inferior colliculus of the guinea pig to
      damped and ramped sinusoids.
AB  - Temporal asymmetry can have a pronounced effect on the perception of a sinusoid.
      For instance, if a sinusoid is amplitude modulated by a decaying exponential that
      restarts every 50 ms, (a damped sinusoid) listeners report a two-component
      percept: a tonal component corresponding to the carrier and a drumming component
      corresponding to the envelope modulation period. When the amplitude modulation is
      reversed in time (a ramped sinusoid) the perception changes markedly; the tonal
      component increases while the drumming component decreases. The long-term Fourier
      energy spectra are identical for damped and ramped sinusoids with the same
      exponential half-life. Modelling studies suggest that this perceptual asymmetry
      must occur central to the peripheral stages of auditory processing (Patterson and
      Irino, 1998). To test this hypothesis, we have recorded the responses of single
      units in the inferior colliculus of the anaesthetised guinea pig. We divided
      single units into three groups: onset, on-sustained and sustained, based on their
      temporal adaptation properties to suprathreshold tone bursts at the unit's best
      frequency. The asymmetry observed in the neural responses of single units was
      quantified in two ways: a simple total spike count measure and a ratio of the
      tallest bin of the modulation period histogram to the total number of spikes.
      Responses were more diverse than those observed with similar stimuli in a
      previous study in the ventral cochlear nucleus (Pressnitzer et al., 2000). The
      main results were: (1) The shape of the responses of on-sustained units to ramped
      sinusoids resembled the shape of the responses to damped sinusoids. This is in
      contrast to the response shapes in the VCN, which were always similar to the
      stimulating sinusoid. (2) Units classified as onsets often responded only to the
      damped stimuli. (3) All units display significant asymmetry in discharge rate for
      at least one of the half-lives tested and 20% showed significant response
      asymmetry over all of the half-lives tested. (4) A summary population measure of
      temporal asymmetry based on total spike count reveals the same pattern of results
      as that obtained psychophysically using the same stimuli (Patterson, 1994a).

PMID- 11520634
TI  - Chronic electrical stimulation of the auditory nerve using high surface area
      (HiQ) platinum electrodes.
AB  - High surface area cochlear implant electrodes with much smaller geometric surface
      areas than current designs might be used in the future to increase the number of
      stimulating electrodes along the carrier. Potential problems with an increase in
      charge density for a common stimulus resulting from decreasing the geometric
      surface area would be reduced by the enlarged real surface area of such
      electrodes. Electrochemically modified (HiQ) platinum (Pt) electrodes, with a
      real surface area approximately 75 times greater than the current standard Pt
      electrodes of the same geometric size, had shown in vitro a low polarization
      (Z(pol)) and electrode impedance (Z(e)), as well as a low residual direct current
      (DC). In this study we examined the chronic performance of HiQ electrodes in
      cats, which were bilaterally implanted with a two-channel HiQ or standard Pt
      scala tympani electrode array and unilaterally stimulated for periods of up to
      2390 h. Stimuli consisted of 50 micros/phase charge-balanced biphasic current
      pulses presented at 2000 pulses/s/channel with a 50% duty cycle. Electrode
      impedance (Z(e)), access resistance (R(a)) and polarization impedance (Z(pol))
      were calculated from current and voltage measurements obtained periodically
      throughout the implantation period. Immediately following implantation HiQ
      electrodes showed a significantly smaller Z(pol), resulting in a reduced Z(e)
      (P<0.0001) compared to standard electrodes, while there was no significant
      difference between R(a) of both electrode designs (P=0.91). Subsequently, Z(e)
      generally increased mainly due to a rise in R(a), which dominated Z(e) and
      obliterated the effect of a lower Z(pol) on Z(e) in HiQ electrodes. Peak R(a)
      levels correlated closely (r=0.85) with the amount of intracochlear fibrous
      tissue found adjacent to the array. Following explantation of the array, voltage
      waveforms for both electrode designs recorded in saline were again very similar
      to those recorded immediately after implantation. Mean DC levels were
      consistently lower for HiQ electrodes compared with standard electrodes (22.45 nA
      vs 134.7 nA). Histopathological examination of corresponding cochlear sections
      comparing the stimulated test side with the unstimulated control side showed no
      significant difference (P>0.05) for either animals implanted with HiQ electrodes
      (n=6) or standard electrodes (n=2). Nor were there any significant differences
      between the spiral ganglion cell density of the basal turn implanted with HiQ or
      standard electrodes for both the stimulated test (P=0.31) and the unstimulated
      control side (P=0.84). Although these findings are based on a small group of
      animals implanted with standard electrodes (n=2), and those negative statistical
      results could potentially be due to the small sample size, similar spiral
      ganglion cell survival was found in a previous study of a larger group of animals
      using standard electrodes stimulated with the same stimulus paradigm as in the
      present study [Xu et al. (1997) Hear. Res. 105, 1-29]. Our data indicate that
      while some initial advantages of HiQ electrodes are lost during chronic
      implantation due to intracochlear fibrous tissue growth, low DC levels and the
      high surface area appear to be maintained, suggesting that HiQ electrodes may
      have important clinical applications.

PMID- 11520635
TI  - Furosemide alters nonlinear capacitance in isolated outer hair cells.
AB  - The outer hair cell (OHC) from the organ of Corti plays a crucial role in hearing
      through its unique voltage-dependent mechanical responses. Furosemide, one of the
      loop diuretics, disrupts normal cochlear function. Here we report on direct
      effects of furosemide on OHC motility-related, voltage-dependent capacitance
      using the whole-cell patch-clamp technique. Extracellularly applied furosemide
      reversibly shifted the voltage at peak capacitance (V(pkC(m))) to positive
      levels. The shift, whose maximum approached 90 mV, evidenced a Hill coefficient
      of 1.5 and K(1/2) of 10 mM. Changes in the magnitude of nonlinear capacitance
      were not fully reversible. While it is clear that the overwhelming effect of
      furosemide on hearing results via its effects on the endolymphatic potential, the
      present results indicate that furosemide directly alters OHC motility and may, in
      part, contribute to sensory dysfunction.

PMID- 11520636
TI  - Detection and intensity discrimination of brief tones as a function of duration
      by hearing-impaired listeners.
AB  - For normal listeners, difference limens for intensity (DLs) for Gaussian-shaped
      tone pulses are largest at medium pulse durations (corresponding to about five
      cycles of the tonal carrier) when the pedestals are 10 dB above threshold, either
      in quiet or in a pink noise background. One explanation for this is that worst
      performance occurs when the internal representation of the tone pulses is most
      compact in time and frequency, affording minimal opportunity for 'multiple looks'
      (Van Schijndel et al., J. Acoust. Soc. Am. 105 (1999) 3425-3435). However, the
      mid-duration worsening is largest for medium overall levels, suggesting an
      involvement of compression on the basilar membrane (BM), which is also greatest
      at medium levels (Baer et al., J. Acoust. Soc. Am. 106 (1999) 1907-1916). If this
      is so, the mid-duration worsening should be reduced when BM compression is
      reduced by outer hair cell damage. To test this, subjects with sensorineural
      hearing losses were tested using 1-kHz or 4-kHz Gaussian-shaped tone pulses, in
      quiet or in pink noise that raised thresholds by 10-20 dB. For subjects with mild
      losses, poorest performance was sometimes found for medium durations. For more
      severe losses, intensity DLs tended to improve monotonically or remain roughly
      constant with increasing duration. Performance overall tended to be better for
      subjects with greater hearing losses. The results are more consistent with an
      explanation based on BM compression than with an explanation based on multiple
      looks.

PMID- 11520637
TI  - Delay analysis in the auditory brainstem of the rat: comparison with click
      latency.
AB  - Many cells in the auditory brainstem 'phase lock' to tone stimuli. From the
      changing phase relationship between the stimulus and the neural response in phase
      locking cells, the delay between them can be estimated. This delay, however, is
      consistently greater than the latency measured in response to click stimuli, an
      important discrepancy. In this paper the different measures of delay, namely
      phase delay, group delay and signal-front delay are re-examined. An improved
      method for computing the average group delay is presented, which accounts for the
      cyclical nature of the phase data. Data were collected from units in successive
      processing sites of auditory pathway: the auditory nerve, the cochlear nucleus,
      the trapezoid body and the medial nucleus of the trapezoid body. Low
      characteristic frequency (CF) units gave multimodal post-stimulus-time histograms
      in response to clicks, and showed stepwise decreases in latency with increasing
      intensity, with the appearance of earlier peaks in the response, rather than
      shifts in the timing of the peaks. The separation of peaks corresponded to the
      inverse of the unit's CF. High-CF units also showed a decline in click latency
      with intensity, but to a lesser degree than low CF units. We present an analysis
      which explains the difference between click latency and delay, and which in
      contrast to previous accounts is experimentally testable. We demonstrate that
      this new framework accounts for the discrepancy between the two measures of
      delay, and in addition accounts for the observed stepwise shifts in click latency
      for low-CF units.

PMID- 11520638
TI  - Temporal processing from the auditory nerve to the medial nucleus of the
      trapezoid body in the rat.
AB  - This investigation examines temporal processing through successive sites in the
      rat auditory pathway: auditory nerve (AN), anteroventral cochlear nucleus (AVCN)
      and the medial nucleus of the trapezoid body (MNTB). The degree of phase-locking,
      measured as vector strength, varied with intensity relative to the cell's
      threshold, and saturated at a value that depended upon stimulus frequency. A
      typical pattern showed decline in the saturated vector strength from
      approximately 0.8 at 400 Hz to about 0.3 at 2000 Hz, with similar profiles in
      units with a range of characteristic frequencies (480-32,000 Hz). A new
      expression for temporal dispersion indicates that this variation corresponds to a
      limiting degree of temporal imprecision, which is relatively consistent between
      different cells. From AN to AVCN, an increase in vector strength was seen for
      frequencies below 1000 Hz. At higher frequencies, a decrease in vector strength
      was observed. From AVCN to MNTB a tendency for temporal coding to be improved
      below 800 Hz and degraded further above 1500 Hz was seen. This change in temporal
      processing ability could be attributed to units classified as primary-like with
      notch (PL(N)). PL(N) MNTB units showed a similar vector strength distribution to
      PL(N) AVCN units. Our results suggest that AVCN PL(N) units, representing
      globular bushy cells, are specialised for enhancing the temporal code at low
      frequencies and relaying this information to principal cells of the MNTB.

PMID- 11520639
TI  - Auditory nerve fiber differences in the normal and neurofilament deficient
      Japanese quail.
AB  - A primary axonal disease affecting the central and peripheral nervous system was
      discovered in a mutant strain of the Japanese quail, named quiver (Quv). We have
      previously demonstrated altered auditory evoked potentials in the neurofilament
      (NF) deficient quail. In this current study we attempt to find relationships
      between the auditory evoked potential results and the histo-pathological
      abnormalities of the auditory neurons. No abnormalities in the external auditory
      meatus and tympanic cavity were observed in either Quv or control quails and the
      ganglion cell bodies and their nuclei appeared normal by light microscopy. The
      myelin staining pattern was found to be similar in both strains with hematoxylin
      and eosin and Kluver-Barrera staining. The frequency histograms of fiber and
      axonal diameters of myelinated fibers showed an unimodal pattern in both strains.
      In Quv quails myelinated fibers and their axoplasm were smaller in diameter than
      in controls resulting in smaller neural tissue mass. In electron microscopic
      observation the axons of the Quv quail were composed of mitochondria and
      microtubules and smooth endoplasmic reticuli. In Quv quail electron micrographs
      of cochlear nerve myelinated fibers NFs were not seen in the axons and the
      neuronal cell bodies. Our current findings indicate that the previously reported
      reduction of conduction velocity of auditory evoked potentials may be due to
      smaller fiber and/or axonal diameter. The g-ratio, myelin thickness and fiber
      circularity were found to be the same for both strains. In conclusion, loss of
      axonal cytoskeletal elements (NFs) correlates well with our electrophysiological
      findings. Reduced conduction velocity and severely distorted auditory evoked
      potentials in NF deficient quails seem to be primarily due to axonal hypotrophy.

PMID- 11520640
TI  - Distribution of immunophilin FKBP-12 protein and mRNA within the mammalian
      cochlea and cochlear nucleus.
AB  - Immunophilin FK binding protein-12 (FKBP-12), the soluble receptor for the
      immunosuppressant drug FK506, is involved in a number of neuronal activities
      including increased nerve regeneration in the peripheral nervous system and
      enhanced recovery in animal models of neurodegenerative diseases. In addition,
      FKBP-12 is tightly bound to the calcium release channel ryanodine receptor and
      physiologically interacts with the inositol 1,4,5-trisphosphate receptor. In
      nearly all cell types, release of intracellular Ca(2+) and subsequent second
      messenger signaling involves activation of these ion channels. We determined the
      distribution of FKBP-12 within the mammalian cochlea and dorsal cochlear nucleus
      (DCN) in order to gain insight into Ca(2+) regulation within the cochlea and to
      possibly identify potential cellular targets for neuroimmunophilin ligands that
      may prove useful in protection and recovery following ototoxic insult. FKBP-12
      protein and mRNA were found to be abundant throughout rat and guinea pig cochlea
      and DCN.

PMID- 11520641
TI  - Modeling temporal and compressive properties of the normal and impaired auditory
      system.
AB  - Three modifications of a psychoacoustically and physiologically motivated
      processing model [Dau et al., J. Acoust. Soc. Am. 102 (1997a) 2892-2905] are
      presented and tested. The modifications aim at simulating sensorineural hearing
      loss and incorporate a level-dependent peripheral compression whose properties
      are affected by hearing impairment. Model 1 realizes this difference by
      introducing for impaired listeners an instantaneous level-dependent expansion
      prior to the adaptation stage of the model. Model 2 and Model 3 realize a level
      dependent compression with time constants of 5 and 15 ms, respectively, for
      normal hearing and a reduced compression for impaired hearing. In Model 2, the
      compression occurs after the envelope extraction stage, while in Model 3,
      envelope extraction follows compression. All models account to a similar extent
      for the recruitment phenomenon measured with narrow-band stimuli and for forward
      masking data of normal-hearing and hearing-impaired subjects using a 20-ms, 2-kHz
      tone signal and a 1-kHz-wide bandpass noise masker centered at 2 kHz. A clear
      difference between the different models occurs for the processing of temporally
      fluctuating stimuli. A modulation-rate-independent increase in modulation
      response level for simulating impaired hearing is only predicted by Model 1 while
      the other two models realize a modulation-rate-dependent increase. Hence, the
      predictions of Model 2 and Model 3 are in conflict with the results of modulation
      matching experiments reported in the literature. It is concluded that key
      properties of sensorineural hearing loss (altered loudness perception, reduced
      dynamic range, normal temporal properties but prolonged forward-masking effects)
      can effectively be modeled by incorporating a fast-acting expansion within the
      current processing model prior to the nonlinear adaptation stage. Based on these
      findings, a model of both normal and impaired hearing is proposed which
      incorporates a fast-acting compressive nonlinearity, representing the cochlear
      nonlinearity (which is reduced in impaired listeners), followed by an
      instantaneous expansion and the nonlinear adaptation stage which represent
      aspects of the retro-cochlear information processing in the auditory system.

PMID- 11520642
TI  - Inter-ear variations in the eardrum impedance and stapes velocity in the human
      middle ear.

PMID- 11520643
TI  - Correlation of impedance at the TM with stapes velocity? Reply to the letter of
      D.H. Keefe.

PMID- 11520644
TI  - Epidemiological research on peripheral vascular disease.

PMID- 11520645
TI  - Prevalence and clinical implications of American Diabetes Association-defined
      diabetes and other categories of glucose dysregulation in older adults: the
      health, aging and body composition study.
AB  - Using data on history of diabetes, fasting glucose (FG) and the oral glucose
      tolerance test (OGTT), the authors contrasted cardiovascular disease (CVD) risk
      factors (body mass index, blood pressure, lipids and glycated hemoglobin) in 3052
      African-American and White adults aged 70-79 in mutually exclusive categories of
      diagnosed diabetes, undiagnosed diabetes defined by the American Diabetes
      Association (ADA), isolated post-challenge hyperglycemia (IPH; FG < 126 mg/dL and
      2 h post-OGTT > or = 200 mg/dL), impaired fasting glucose (IFG; FG > or = 110 but
      < 126 mg/dL), and individuals who were non-diabetic by both ADA and World Health
      Organization (WHO) criteria (FG < 126 mg/dL and 2 h post-challenge glucose < 200
      mg/dL). The prevalence of diagnosed diabetes, undiagnosed ADA diabetes and IPH
      were 15.2, 3.8 and 4.7%, respectively, with more diagnosed and undiagnosed ADA
      diabetes in African-Americans than Whites. Compared to mean glycated hemoglobin
      (HbA(1c)) among ADA/WHO non-diabetic individuals (6.0%), HbA(1c) was
      substantially higher in the diagnosed diabetes and undiagnosed ADA diabetes
      groups (8.0% and 7.7%), but not in the IPH group (6.3%). The diagnosed and
      undiagnosed ADA diabetic groups had worse CVD risk factor profiles than the
      ADA/WHO non-diabetic group. IPH subjects had elevated levels of some CVD risk
      factors, but differences were more modest than those for the diabetic groups.
      Among people with IPH, those who also had IFG had worse CVD profiles than those
      with IPH alone. Although the OGTT may identify additional adults with more CVD
      risk factors than normals, these differences appear to be clustered among those
      who also have IFG.

PMID- 11520646
TI  - Patterns of patient enrollment in randomized controlled trials.
AB  - We aimed to describe enrollment patterns in a large cohort of randomized
      controlled trials (RCTs) and evaluate whether early recruitment predicts the
      ability of RCTs to reach their target enrollment. We considered all 77 efficacy
      RCTs initiated by the AIDS Clinical Trials Group between 1986 and 1996 (28,992
      patients enrolled until November 1999). Thirteen RCTs (17%) failed to reach half
      their target recruitment. Enrollment trajectories showed that the initial rate of
      accrual determined the subsequent rates of enrollment. The target sample size was
      attained by 7/8, 11/14, 15/35 and 4/20 of trials with very rapid, rapid, moderate
      and slow enrollment during the first 3 months, respectively (P < 0.001).
      Enrollment during the first month or two strongly correlated with subsequent
      accrual (P < 0.001). The patient pool, the eligibility criteria, the
      attractiveness of a trial and adequacy of the network of clinical sites may
      influence RCT enrollment. Early enrollment offers strong evidence on the
      feasibility of a trial and is indicative of its future pace of recruitment.

PMID- 11520647
TI  - Retrospective classification of prostate-specific antigen tests: differentiating
      screening from diagnostic clinical encounters.
AB  - To assess the validity of retrospective medical chart review as a method of
      classifying prostate-specific antigen (PSA) tests as screening or diagnostic
      services, we reviewed PSA tests ordered at a university hospital (n = 95). PSA
      tests were reviewed by four raters: medicine resident (RES), oncologist (ONC),
      urologist (UR), medicine attending (GM)-and the physician who ordered the PSA
      test (ATTEND) using predefined standardized criteria. Agreement rates by
      individual rater and ATTEND were 0.79 (GM), 0.80 (ONC), 0.74 (UR), 0.83 (RES),
      for a composite percent agreement of 0.79. ATTEND incorrectly classified seven
      tests; exclusion of these tests raised agreement rates to 0.86 (GM), 0.86 (ONC),
      0.80 (UR), 0.90 (RES), for a group composite percent agreement of 0.86. Of note,
      two raters had higher agreement rates when evaluating screening PSA tests than
      when evaluating diagnostic PSA tests. Standardized criteria applied to medical
      charts provide a valid method of retrospectively classifying PSA tests.

PMID- 11520648
TI  - Self-reported preclinical disability identifies older women with early declines
      in performance and early disease.
AB  - There appears to be a preclinical stage of physical disability which precedes
      onset of task difficulty (disability) in those who develop disability
      progressively as a result of chronic disease. Such a stage provides a basis for
      identifying older adults at risk of becoming disabled. This cross-sectional study
      evaluated whether a preclinical stage of physical function identified by self
      report is associated with decrements in objective physical performance measures
      or increases in disease; that is, whether these measures, in those with
      preclinical disability, are intermediate between individuals who report no
      difficulty and no preclinical changes and those who report difficulty. The
      Women's Health and Aging Study II, an observational study of 436 women 70-80
      years of age who were among the two-thirds least disabled living in the
      community. Participants were sampled from the HCFA Medicare eligibility lists and
      were determined eligible if they reported no difficulty, or difficulty in only
      one of four domains of physical function: mobility, upper extremity, IADL and ADL
      tasks. At the first follow-up (18 months after baseline), participants completed
      questionnaires on physical functioning for tasks in each of these domains, with
      possible answer options for each task: they had (1) difficulty (disabled); (2) no
      difficulty and no modification of task performance (High Function); or (3) no
      difficulty but reported modification and/or change in frequency of task
      performance (a self-report measure of preclinical disability predictive of
      incident difficulty). At the same visit, standardized, objective measures of
      function and disease were obtained, including measured walk; chair stands;
      strength: hip flexion, knee extension, ankle dorsiflexion, and grip; balance:
      function reach, single leg stand, tandem stand; joint exam: hip pain on passive
      motion and knee pain or tenderness; spirometry; ankle:arm blood pressure ratio;
      visual function: acuity, contrast sensitivity, stereopsis; and graded treadmill
      exercise test. Data were analyzed from the first follow-up examination. Physical
      performance decreased, and disease frequency increased, in association with
      decreasing self-reported mobility function (in walking one-half mile and climbing
      10 steps), across three self-report categories: High Function, Preclinical
      Disability (Task Modification but No Difficulty) and Disability (Difficulty).
      These findings pertained for measures of walking speed, balance, strength, and
      knee and hip osteoarthritis. Self-reported level of function predicted
      differences in ranges as well as means for walking speed, balance and strength.
      These findings indicate a physiologic basis for self-reported function, including
      preclinical disability, specifically that different levels of disease severity,
      impairments and physical performance are concurrently associated with different
      categories of self-reported function. They also suggest new avenues for screening
      and intervention to prevent disability.

PMID- 11520649
TI  - Reliability of data on medical conditions, menstrual and reproductive history
      provided by hospital controls.
AB  - To assess the reliability of data on medical conditions, and menstrual or
      reproductive history, a sample of 294 controls interviewed in hospital between
      1989 and 1992 for an Italian case-control study on digestive tract neoplasms was
      re-interviewed at home during 1993. A high agreement between responses at the two
      interviews (kappa > or = 0.85) was observed for most medical conditions,
      including diabetes, cholelithiasis, hepatitis, duodenal ulcer, and, among female
      conditions, uterine fibromas, benign breast disease, hysterectomy and monolateral
      ovariectomy. For gastric ulcer and parotitis the reliability was less
      satisfactory (kappa = 0.35 and 0.20, respectively). The agreement was high (kappa
      > 0.80) also for age at menarche, menopausal status, type and age at menopause,
      number of children, age at first pregnancy, age at first and last birth, and
      spontaneous abortions. The agreement was lower for questions on menstrual pattern
      (kappa = 0.68) and induced abortions (kappa = 0.62). Thus, this study indicates
      that information on personal medical conditions, and menstrual or reproductive
      history, provided by hospital controls through an interviewer-administered
      questionnaire is satisfactory for the purposes of epidemiological inference, and
      that the interview setting does not substantially influence the recall of this
      information.

PMID- 11520650
TI  - The UK version of the Seattle Angina Questionnaire (SAQ-UK): reliability,
      validity and responsiveness.
AB  - The study assesses the reliability, validity and responsiveness of the UK version
      of the Seattle Angina Questionnaire (SAQ-UK). The instrument was anglicised and
      administered by self-completed postal questionnaire to 959 patients recruited
      from general practices in the North East of England. A total of 655 (68.3%)
      patients returned a completed questionnaire. Principal component analysis
      produced three important dimensions: physical limitations, anginal frequency and
      perception and treatment satisfaction. Four items that performed poorly were
      removed from the instrument. The removal of items greatly increased the number of
      computable scale scores. Estimates of internal reliability for the three
      dimensions ranged from 0.83-0.92. Estimates of test-retest reliability were above
      accepted standards. The correlation between the SAQ-UK scores and the SF-12,
      EuroQol and health transition was evidence for the validity of the instrument.
      The SAQ-UK produced responsiveness statistics that were comparable to the parent
      instrument and was more responsive to improvements in health than the generic
      instruments. The SAQ-UK is recommended as a measure of health outcome for the
      evaluation of angina management.

PMID- 11520651
TI  - Original article underweight, overweight and obesity: relationships with
      mortality in the 13-year follow-up of the Canada Fitness Survey.
AB  - The purpose of this study was to determine the risk of all-cause mortality in the
      Canadian population across the new WHO/NIH BMI categories for the classification
      of overweight and obesity. The sample includes 10,725 adult participants (20-69
      years) in the 1981 Canada Fitness Survey. A total of 593 deaths occurred during
      13 years of follow-up. Hazard ratios (HR) for mortality were estimated using Cox
      proportional hazards models. Compared to normal weight individuals, there is an
      increased risk of mortality in the underweight category (HR 1.63, 95% CI 0.93
      2.85) in addition to increasing levels of risk across the overweight (HR 1.16,
      95% CI 0.96-1.39), obese class I (HR 1.25, 95% CI 0.96-1.65) and obese class II
      and III (HR 2.96, 95% CI 1.39-6.29) categories. Similar patterns were observed in
      sex-specific analyses. Underweight, overweight and obese Canadians are all at
      increased risk of mortality compared to those who are normal weight.

PMID- 11520652
TI  - Sociodemographic factors and trends on overweight prevalence in children and
      adolescents in Aragon (Spain) from 1985 to 1995.
AB  - From 1985 to 1995, the Aragon School Health Examination Surveys staff has
      surveyed the whole population of children (age 6-7 years) and adolescents (age 13
      14 years). A total of 90,997 children (age 6-7 years) were examined in the nine
      cross-sectional surveys conducted between 1985 and 1995. A total of 106,284
      adolescents (age 13-14 years) were also examined. We defined overweight when the
      body mass index was > or = 95th percentile. The measure of association between
      overweight and the other variables studied was the odds ratio, which was
      calculated by logistic regression. In the children and adolescents studied, the
      probability to be overweight was higher in the rural than in the urban areas. In
      the adolescents, the probability to be overweight was higher in the public than
      in the private schools. Our results also show a significant increase in the
      prevalence of overweight children in the region of Aragon (Spain) during the 1985
      1995 decade, especially in males. Prevention of overweight in the populations at
      risk would help reduce social inequality in health, a major challenge for public
      health policy.

PMID- 11520653
TI  - Prevalence and outcomes of comorbid metabolic and cardiovascular conditions in
      middle- and older-age adults.
AB  - To estimate age group differences in the prevalence and outcomes of three common
      and often comorbid metabolic conditions (i.e., obesity, hypertension, and
      diabetes) and heart disease. DESIGN: Nationally representative prospective cohort
      study. SETTING: PARTICIPANTS' homes. PARTICIPANTS: 9825 adults aged 51 to 61
      years (middle-age) in 1992, and 7370 adults aged 70 years and over (older-age) in
      1993. MEASUREMENTS: Two-year dichotomous outcomes included: doctor visits,
      hospitalization, mobility difficulty, activity of daily living limitation, poor
      perceived health, and mortality. Odds ratios (OR) were adjusted for
      sociodemographic characteristics and history of cancer or lung disease. RESULTS:
      Those with one condition represented 80% and 70% of the middle- and older-age
      groups, respectively, while just 1-2% of each age group reported all three
      metabolic conditions. Thirteen percent and 32%, respectively, reported heart
      disease with or without metabolic conditions. Diabetes comorbid with other
      metabolic conditions, and particularly with heart disease, substantially elevated
      the risk of adverse outcomes such as health-related quality of life deficits,
      health services use, and mortality in both middle- and older-age adults. In the
      middle-age group, the OR was 6.81 for mortality in patients with a combination of
      obesity and diabetes and 6.10 in those with a combination of heart disease and
      diabetes. There also were significant ORs for mortality in middle-aged patients
      with heart disease (OR = 2.40), diabetes (OR = 2.63) and for those with a
      combination of obesity, hypertension, and diabetes (OR = 3.26). CONCLUSION: The
      impact of these often comorbid conditions underscores the importance of targeted
      and aggressive prevention, particularly among middle-age adults.

PMID- 11520654
TI  - Risk factors for clinical benign prostatic hyperplasia in a community-based
      population of healthy aging men.
AB  - We defined risk factors for a clinical diagnosis of benign prostatic hyperplasia
      (BPH) among subjects of the population-based Massachusetts Male Aging Study. In
      1987-89 1709 men aged 40-70 provided baseline risk factor data and were followed
      for a mean of 9 years; 1019 men without prostate cancer provided follow-up data.
      We classified men with clinical BPH at follow-up if they reported (1) frequent or
      difficulty urinating and were told by a health professional that they had an
      enlarged or swollen prostate or (2) if they reported having surgery for BPH. At
      follow-up the prevalence of clinical BPH was 19.4%, increasing from 8.4% of men
      aged 38-49 years to 33.5% of men aged 60-70 years (P < 0.001 for trend). Elevated
      free PSA levels (age- and total PSA-adjusted OR, top vs. bottom quartile ng/mL
      4.4, 95% CI 1.9-10.5), heart disease (age-adjusted OR 2.1, CI 1.3-3.3), and use
      of beta-blocker medications (OR 1.8, CI 1.1-3.0) increased odds for BPH, while
      current cigarette smoking (OR 0.5, CI 0.3-0.8) and high levels of physical
      activity (top vs. bottom quartile kcals/day OR 0.5, CI 0.3-0.9) decreased odds of
      BPH. All but the medication effects persisted in fully adjusted multivariable
      models. Total or fat calorie intake, sexual activity level, alcohol intake, body
      mass index, waist-hip ratio, diastolic blood pressure, a history of diabetes,
      hypertension, vasectomy, or serum levels of androgens or estrogens did not
      individually predict clinical BPH. We conclude that physical exercise and
      cigarette smoking appear to protect against development of clinical BPH. Elevated
      free PSA levels predict clinical BPH independent of total PSA levels. Risk
      associated with heart disease does not appear to be due solely to detection bias
      or to effects of heart disease medications. A wide variety of other
      characteristics appear to have no influence on risk for clinical BPH.

PMID- 11520655
TI  - Test validity of periodic liver function tests in a population of Japanese male
      bank employees.
AB  - The validity (sensitivity and specificity) of annual liver function tests,
      determined by assaying blood levels of aspartate aminotransferase, alanine
      aminotransferase and gammaglutamyl transpeptidase, was evaluated using the
      results of health checkups of male bank workers. The specificity of each liver
      function test to detect persons with fatty liver, excess alcohol users, and
      hepatic virus carriers, diagnosed respectively by ultrasound, detailed inquiry,
      and virus marker tests, was always higher than 80%, except for alanine
      aminotransferase in excess alcohol users (63.5%). However, the highest
      sensitivity to detect virus carriers was alanine aminotransferase to detect HCV
      antibody-positive workers, but it was only 45.5%. The highest sensitivity of the
      liver function tests to detect excess alcohol users in obese subjects was only
      33.3%. The highest sensitivity by liver function tests to detect fatty liver was
      35.7% which was inferior to that of the body mass index. These results indicate
      that the liver function tests mandated in the workplace periodic health checkups
      in Japan exhibit very low sensitivity for the detection of any of the proposed
      target clinical conditions.

PMID- 11520656
TI  - Quality of life: an index for identifying high-risk cardiac patients.
AB  - A sample of 945 cardiac patients admitted under emergency conditions completed a
      quality of life questionnaire 4 months post-discharge. Half (471) were randomly
      allocated to a group used to develop a logistic regression model to predict
      mortality and cardiovascular morbidity 8 months later. Age 65-85 years, ever
      having heart failure, experiencing another cardiovascular event since discharge,
      and low global quality of life (QOL) score were found to be predictive of these
      outcomes; an interaction between QOL and heart failure was also found. The model
      was used to formulate a risk index which was validated in the remaining 474
      patients. The index defines four levels of increasing risk of adverse outcomes,
      with rates in the development and validation groups, respectively, of: low risk
      4% and 9%; moderate risk 13% and 15%; high risk 31% and 33%; very high risk 52%
      and 40%. Scores in the emotional, physical and social QOL domains were also found
      to be predictive of adverse outcomes, suggesting that interventions in any of
      these areas may prove beneficial. The index may be useful for follow-up
      evaluation of cardiac patients.

PMID- 11520657
TI  - Clinical significance of falling blood pressure among older adults.
AB  - We assessed the prevalence of falling blood pressure among older adults and its
      relationship to subsequent outcomes, using public use data from four sites of the
      Established Populations for Epidemiologic Studies of the Elderly. Seventeen
      percent of subjects had a decrease in systolic blood pressure of 20 mm Hg or
      greater and 22% had a decrease in diastolic blood pressure of 10 mm Hg or greater
      between year 0 and year 3. Falling systolic and diastolic blood pressure was
      associated with increased all-cause mortality (OR 1.5, 95% CI 1.3, 1.7),
      cardiovascular mortality (OR 1.6, 95% CI 1.3, 1.9) and all cardiovascular events
      (OR 1.4, 95% CI 1.2, 1.6) in the subsequent 3 years (years 4 to 6). Increasing
      amount of fall in blood pressure was associated with increasing risk of
      mortality. The magnitude of effect of falling blood pressure on adverse outcomes
      declined and became nonsignificant after adjusting for comorbidity and functional
      status at baseline. Thus, falling blood pressure is common among older adults and
      is a marker for underlying poor health and subsequent mortality.

PMID- 11520658
TI  - A new model of integrated home care for the elderly: impact on hospital use.
AB  - The objective of the present study was to examine the effect of a home care
      program based on comprehensive geriatric assessment-Minimum Data Set for Home
      Care-and case management on hospital use/cost of frail elderly individuals. We
      determined all hospital admissions and days spent in hospital during the first
      year since the implementation of the home care program, and compared them to the
      rate of hospitalization that the same patients had experienced in the year
      preceding the implementation of such program. Following the implementation of
      this program, there was a significant reduction of the number of hospitalizations
      (pre 44% vs. post 26%, P < 0.001), associated with a reduction of hospital days,
      both at the individual patient level and for each admission. In conclusion, an
      integrated home care program based on the implementation of a comprehensive
      geriatric assessment instrument guided by a case manager has a significant impact
      on hospitalization and is cost-effective.

PMID- 11520659
TI  - Embryonic regionalization of the neocortex.
AB  - Understanding the development of the vertebrate brain and in particular that of
      the neocortex, where high brain functions reside, remains one of the most
      difficult and exciting tasks in biology. In this review, we discuss recent
      experimental evidence as well as different possibilities for the intrinsic
      regionalization of the embryonic dorsal telencephalon, which may be related to
      the formation of distinct functional areas in the adult neocortex.

PMID- 11520660
TI  - Function of the Drosophila TGF-alpha homolog Spitz is controlled by Star and
      interacts directly with Star.
AB  - Drosophila Spitz is a homolog of transforming growth factor alpha (TGF-alpha) and
      is an activating ligand for the EGF receptor (Egfr). It has been shown that Star
      is required for Spitz activity. Here we show that Star is quantitatively limiting
      for Spitz production during eye development. We also show that Star and Spitz
      proteins colocalize in Spitz sending cells and that this association is not
      coincident with the site of translation--consistent with a function for Star in
      Spitz processing or transmission. Finally, we have defined minimal sequences
      within both Spitz and Star that mediate a direct interaction and show that this
      binding can occur in vivo.

PMID- 11520661
TI  - A novel sox gene, 226D7, acts downstream of Nodal signaling to specify endoderm
      precursors in zebrafish.
AB  - Vertebrate endoderm development has recently become the focus of intense
      investigation. We have identified a novel sox gene, 226D7, which is important in
      zebrafish endoderm development. 226D7 was isolated by an in situ hybridization
      screening for genes expressed in the yolk syncytial layer (YSL) at the blastula
      stage. 226D7 is expressed mainly in the YSL at this stage and, during
      gastrulation, its expression is also detected in the forerunner cells and
      endodermal precursor cells. The expression of 226D7 is positively regulated by
      Nodal signaling. The knockdown of 226D7 using morpholino antisense
      oligonucleotides results in a lack of sox17-expressing endodermal precursor cells
      during gastrulation, and, consequently, lacks endodermal derivatives such as gut
      tissue. The effect is strictly restricted to the endodermal lineage, while the
      mesoderm is normally formed, a phenotype that is nearly identical to that of the
      casanova mutant (Dev. Biol. 215 (1999) 343). We further demonstrate that
      overexpression of 226D7 increases the number of sox17-expressing endodermal
      progenitor cells without upregulating the expression of the Nodal genes, cyclops
      and squint. Region-specific knockdown and overexpression of 226D7 by injection
      into the YSL suggest that 226D7 in the YSL is not involved in endoderm formation
      and 226D7 in the endoderm progenitor cells is important for endoderm development.
      Taken together, our data demonstrate that 226D7 is a downstream target of Nodal
      signal and a critical transcriptional regulator of early endoderm formation.

PMID- 11520662
TI  - The nuclear receptor Ftz-F1 and homeodomain protein Ftz interact through
      evolutionarily conserved protein domains.
AB  - The Drosophila homeodomain protein Fushi Tarazu (Ftz) and its partner, the orphan
      receptor Ftz-F1, are members of two distinct families of DNA binding
      transcriptional regulators. Ftz and Ftz-F1 form a novel partnership in vivo as a
      Hox/orphan receptor heterodimer. Here we show that the murine Ftz-F1 ortholog SF
      1 functionally substitutes for Ftz-F1 in vivo, rescuing the defects of ftz-f1
      mutants. This finding identified evolutionarily conserved domains of Ftz-F1 as
      critical for activity of this receptor in vivo. These domains function, at least
      in part, by mediating direct protein interactions with Ftz. The Ftz-F1 DNA
      binding domain interacts strongly with Ftz and dramatically facilitates the
      binding of Ftz to target DNA. This interaction is augmented by a second
      interaction between the AF-2 domain of Ftz-F1 and the N-terminus of Ftz via an
      LRALL sequence in Ftz that is reminiscent of LXXLL motifs in nuclear receptor
      coactivators. We propose that Ftz-F1 serves as a cofactor for Ftz by facilitating
      the selection of target sites in the genome that contain Ftz/Ftz-F1 composite
      binding sites. Ftz, on the other hand, influences Ftz-F1 activity by interacting
      with its AF-2 domain in a manner that mimics a nuclear receptor coactivator.

PMID- 11520663
TI  - An in situ screen for genes controlling cell proliferation in the optic tectum of
      the medaka (Oryzias latipes).
AB  - The optic tectum is a dorsal, prominent and well corticalised structure of the
      fish brain. It grows according to a pattern exceptional in the vertebrate central
      nervous system, by addition of radial columns of cells at its periphery. We took
      advantage of this peculiar feature to readily identify genes differentially
      expressed in the tectal proliferative (marginal) vs. post-mitotic (central)
      zones. Out of 500 medaka cDNA clones screened by WMISH, more than 100 were
      expressed in one or the other of these zones. Unexpectedly, we also identified a
      small class of genes expressed between these two zones. All the characterised
      genes of this class encode down regulators of the cell cycle. Therefore, such a
      screening strategy allows in particular cases to raise testable hypotheses on the
      involvement of genes in the control of the cell cycle, in addition to
      characterising unknown genes with patterned expression related to cell
      proliferation.

PMID- 11520664
TI  - Characterization of Wnt gene expression in developing and postnatal hair
      follicles and identification of Wnt5a as a target of Sonic hedgehog in hair
      follicle morphogenesis.
AB  - Mutations in WNT effector genes perturb hair follicle morphogenesis, suggesting
      key roles for WNT proteins in this process. We show that expression of Wnts 10b
      and 10a is upregulated in placodes at the onset of follicle morphogenesis and in
      postnatal hair follicles beginning a new cycle of hair growth. The expression of
      additional Wnt genes is observed in follicles at later stages of differentiation.
      Among these, we find that Wnt5a is expressed in the developing dermal condensate
      of wild type but not Sonic hedgehog (Shh)-null embryos, indicating that Wnt5a is
      a target of SHH in hair follicle morphogenesis. These results identify candidates
      for several key follicular signals and suggest that WNT and SHH signaling
      pathways interact to regulate hair follicle morphogenesis.

PMID- 11520665
TI  - Identification of ephrin-A3 and novel genes specific to the midbrain-MHB in
      embryonic zebrafish by ordered differential display.
AB  - Development of the tectum and the cerebellum is induced by a reciprocal inductive
      signaling between their respective primordia, the midbrain and the
      midbrain/hindbrain boundary (MHB). We set out to identify molecules that function
      in and downstream of this reciprocal signaling. Overexpression of LIM domain of
      the transcription factor Islet-3 (LIM(Isl-3)) leads to inhibition of this
      reciprocal signaling and to resultant defects in tectal and cerebellar
      development. We therefore searched for genes that may be either up- or down
      regulated by overexpression of LIM(Isl-3) by comparing the gene expression
      profiles in the midbrain and the MHB of normal embryos and embryos in which Islet
      3 function was repressed, using a combination of ordered differential display and
      whole-mount in situ hybridization. Among genes identified in this search, two
      cDNA fragments encoded Wnt1 and FGF8, which are already known to be essential for
      the reciprocal signaling between the midbrain and the MHB, confirming the
      effectiveness of our strategy. We identified four other partial cDNA clones that
      were specifically expressed around the MHB, ten cDNAs specifically expressed in
      the tectum, and three cDNAs expressed in neural crest cells including those
      derived from the midbrain level. The ephrin-A3 gene was specifically expressed in
      posterior tectum in a gradient that decreased anteriorly. Although ephrin-A2 and
      ephrin-A5 have been reported to be expressed in the corresponding region in mouse
      embryos, the superior/inferior colliculi, mouse ephrin-A3 is not expressed
      prominently in this region, suggesting that the role of ephrin-A3 in brain
      development may have been altered in the process of brain evolution.

PMID- 11520666
TI  - Tudor protein is essential for the localization of mitochondrial RNAs in polar
      granules of Drosophila embryos.
AB  - In Drosophila, polar plasm contains polar granules, which deposit the factors
      required for the formation of pole cells, germ line progenitors. Polar granules
      are tightly associated with mitochondria in early embryos, suggesting that
      mitochondria could contribute to pole cell formation. We have previously reported
      that mitochondrial large and small rRNAs (mtrRNAs) are transported from
      mitochondria to polar granules prior to pole cell formation and the large rRNA is
      essential for pole cell formation. Here we show that the localization of mtrRNAs
      is diminished in embryos laid by tudor mutant females, although the polar
      granules are maintained. We also found that Tud protein was colocalized with
      mtrRNAs at the boundaries between mitochondria and polar granules when the
      transport of mtrRNAs takes place. These observations suggest that Tud mediates
      the transport of mtrRNAs from mitochondria to polar granules.

PMID- 11520667
TI  - Tight transcriptional control of the ETS domain factors Erm and Pea3 by Fgf
      signaling during early zebrafish development.
AB  - Several molecules of the Fibroblast growth factor family have been implicated in
      the development of the vertebrate brain, but the effectors of these molecules
      remain largely unknown. Here we study Erm and Pea3, two ETS domain transcription
      factors, and show that their expression correlates closely with the domains of
      fgf8 and fgf3 expression. In situ hybridization analysis in wild-type and
      acerebellar (ace) mutant embryos defective for fgf8 demonstrates a requirement of
      Fgf8 for normal expression levels of erm and pea3 transcripts in and close to
      various domains of Fgf8 action, including the prospective midbrain-hindbrain
      region, the somites, the neural crest, the forebrain, and developing eyes.
      Morpholino-oligomer-assisted gene knock-down experiments targeted against fgf8
      and fgf3 suggest that Fgf3 and Fgf8 are co-regulators of these genes in the early
      forebrain anlage. Furthermore, inhibition of Fgf signaling by overexpression of
      sprouty4 or application of the Fgf inhibitor SU5402 leads to a loss of all erm
      and pea3 expression domains. Conversely, ectopically provided fgf3 mRNA or
      implanted beads coated with Fgf8 elicit ectopic transcription of erm and pea3.
      Both activation and loss of transcripts can be observed within short time frames.
      We conclude that both the transcriptional onset and maintenance of these factors
      are tightly coupled to Fgf signaling and propose that erm and pea3 transcription
      is a direct readout of cells to Fgf levels. Given the knowledge that has
      accumulated on the posttranslational control of ETS domain factors and their
      combinatorial interactions with other transcription factors, we suggest that the
      close coupling of erm and pea3 transcription to Fgf signaling might serve to
      integrate Fgf signaling with other signals to establish refined patterns in
      embryonic development.

PMID- 11520668
TI  - The Alzheimer-related gene presenilin-1 facilitates sonic hedgehog expression in
      Xenopus primary neurogenesis.
AB  - We analyzed the influence of presenilins on the genetic cascades that control
      neuronal differentiation in Xenopus embryos. Resembling sonic hedgehog (shh)
      overexpression, presenilin mRNA injection reduced the number of N-tubulin+
      primary neurons and modulated Gli3 and Zic2 according to their roles in
      activating and repressing primary neurogenesis, respectively. Presenilin
      increased shh expression within its normal domain, mainly in the floor plate,
      whereas an antisense X-presenilin-alpha morpholino oligonucleotide reduced shh
      expression. Both shh and presenilin promoted cell proliferation and apoptosis,
      but the effects of shh were widely distributed, while those resulting from
      presenilin injection coincided with the range of shh signaling. We suggest that
      presenilin may modulate primary neurogenesis, proliferation, and apoptosis in the
      neural plate, through the enhancement of shh signaling.

PMID- 11520669
TI  - Delta regulates keratinocyte spreading and motility independently of
      differentiation.
AB  - In human interfollicular epidermis stem cells lie in clusters surrounded by their
      differentiated daughters, transit amplifying cells, an arrangement that reflects
      differences in cell cohesiveness and motility. Keratinocytes expressing a
      dominant negative Delta1 mutant, Delta(T), lacking most of the cytoplasmic
      domain, acquired the motile behaviour of transit cells while retaining their stem
      cell identity. Conversely, overexpression of Delta1 promoted keratinocyte
      cohesiveness. The adhesive effects of Delta1 and Delta(T) were independent of SuH
      dependent Notch signalling. Delta(T) increased motility and spreading of
      individual keratinocytes and stimulated lamellipodia formation. Delta and
      Delta(T) colocalised with cortical actin and redistributed on Latrunculin
      treatment. We propose that Delta promotes keratinocyte cohesiveness by
      restricting motility and discuss potential mechanisms by which Delta could
      interact with the actin cytoskeleton.

PMID- 11520670
TI  - Over-expression of the SUV39H1 histone methyltransferase induces altered
      proliferation and differentiation in transgenic mice.
AB  - The development of multi-cellular organisms is regulated by the ordered
      definition of gene expression programmes that govern cell proliferation and
      differentiation. Although differential gene activity is mainly controlled by
      transcription factors, it is also dependent upon the underlying chromatin
      structure, which can stabilize transcriptional "on" or "off" states. We have
      recently isolated human (SUV39H1) and mouse (Suv39h1) histone methyltransferases
      (HMTases) and shown that they are important regulators for the organization of
      repressive chromatin domains. To investigate whether a SUV39H1-induced modulation
      of heterochromatin would affect mammalian development, we generated transgenic
      mice that over-express the SUV39H1 HMTase early during embryogenesis. SUV39H1
      transgenic mice are growth retarded, display a weak penetrance of skeletal
      transformations and are largely characterized by impaired erythroid
      differentiation, consistent with highest transgene expression in foetal liver. Ex
      vivo transgenic foetal liver cultures initially contain reduced numbers of cells
      in G1 but progress to immortalized erythroblasts that are compromised in
      executing an erythroid differentiation programme. The outgrowing SUV39H1
      immortalized erythroblasts can maintain a diploid karyotype despite deregulation
      of several tumour suppressor proteins and dispersed distribution of the
      heterochromatin component HP1. Together, these data provide evidence for a role
      of the SUV39H1 HMTase during the mammalian development and indicate a possible
      function for higher-order chromatin in contributing to the balance between
      proliferation and differentiation potentials of progenitor cells.

PMID- 11520671
TI  - Slit1 is specifically expressed in the primary and secondary enamel knots during
      molar tooth cusp formation.
AB  - The shape and diversity of the mammalian molar teeth is suggested to be regulated
      by the primary and secondary enamel knots, which are putative epithelial
      signaling centers of the tooth. In search of novel molecules involved in tooth
      morphogenesis, we analyzed mRNA expression of Slit1, -2 and -3, earlier
      characterized as secreted signals needed for axonal pathfinding and their two
      receptors Robo1 and -2 (Roundabout1 and -2) in the developing mouse first molar.
      In situ hybridization analysis showed that Slit1 mRNAs were expressed in the
      primary enamel knot of the bud and cap stage tooth germ and later the expression
      continued in the secondary enamel knots of the late cap and bell stage tooth. In
      contrast, expression of Slit2 and -3 as well Robo1, and -2 was largely restricted
      to mesenchymal tissue components of the tooth until the bell stage. At the late
      bud stage, however, Robo1 transcripts were evident in the primary enamel knot,
      and at the cap stage a pronounced expression was noted in the middle of the tooth
      germ covering the primary enamel knot and dental papilla mesenchyme. During the
      bell stage, Robo1 and Slit2 expression became restricted to the dental epithelia,
      while Slit3 continued in the dental mesenchyme. Prior to birth, Robo1 and -2 were
      co-localized in the predontoblasts. These results indicate that Slits and Robos
      display distinct, developmentally regulated expression patterns during tooth
      morphogenesis. In addition, our results show that Slit1 is the second known gene
      specifically located in the primary and secondary enamel knots.

PMID- 11520672
TI  - ske-T, a T-box gene expressed in the skeletogenic mesenchyme lineage of the sea
      urchin embryo.
AB  - T-box transcription factors regulate many developmental processes. Here we report
      the cloning and expression analysis of ske-T, a novel sea urchin T-box gene. The
      distribution of the maternal ske-T transcript is uniform in the egg and early
      embryonic stages while zygotic expression is restricted to the skeletogenic
      mesenchyme lineage.

PMID- 11520673
TI  - Expression patterns of group-I aristaless-related genes during craniofacial and
      limb development.
AB  - Aristaless-related proteins are structurally defined by the presence of a paired
      type homeodomain and an additional conserved domain, known as aristaless domain
      or OAR-domain. These proteins can be further categorized in three groups (Int. J.
      Dev. Biol., 43 (1999) 651). Group-I aristaless-related genes are linked to
      functions in the development of the craniofacial and appendicular skeleton and
      are expressed predominantly in the mesenchyme in stages from gastrulation through
      at least mid-gestation (Mech. Dev., 48 (1994) 245; Mech. Dev., 52 (1995) 51;
      Development, 124 (1997) 3999; Dev. Biol., 199 (1998) 11; Development, 126 (1999)
      495). In view of the highly redundant character of the functions of these genes
      in patterning craniofacial and limb structures, we found it important to directly
      compare their expression patterns at critical stages of craniofacial and limb
      development.

PMID- 11520674
TI  - Gene and cluster-specific expression of the Iroquois family members during mouse
      development.
AB  - Mammalian homologues of the Drosophila Iroquois homeobox gene complex, involved
      in patterning and regionalization of differentiation, have recently been
      identified (Mech. Dev., 69 (1997) 169; Dev. Biol., 217 (2000) 266; Dev. Dyn., 218
      (2000) 160; Mech. Dev., 91 (2000) 317; Dev. Biol., 224 (2000) 263; Genome Res.,
      10 (2000) 1453; Mech. Dev., 103 (2001) 193). The six members of the murine family
      were found to be organized in two cognate clusters of three genes each, Irx1, -2,
      -4 and Irx3, -5, -6, respectively (Peters et al., 2000). As a basis for further
      study of their regulation and function we performed a comparative analysis of the
      genomic organization and of the expression patterns of all six Irx genes. The
      genes are expressed in highly specific and regionalized patterns of ectoderm,
      mesoderm and endoderm derived tissues. In most tissues the pattern of expression
      of the clustered genes, especially of Irx1 and -2 and of Irx3 and -5,
      respectively, closely resembled each other while those of Irx4 and -6 were very
      divergent. Interestingly, the expression of cognate genes was found to be
      mutually exclusive in adjacent and interacting tissues of limb, heart and the
      laryncho-pharyncheal region. The results indicate that the Irx genes are
      coordinately regulated at the level of the cluster.

PMID- 11520675
TI  - Osr2, a new mouse gene related to Drosophila odd-skipped, exhibits dynamic
      expression patterns during craniofacial, limb, and kidney development.
AB  - We have isolated a new mouse gene, odd-skipped related 2 (Osr2), that encodes a
      zinc finger containing protein related to Drosophila Odd-skipped. The putative
      OSR2 protein shares 65% amino acid sequence identity overall and 98% sequence
      identity in the zinc finger region, respectively, with the previously reported
      Osr1 gene product. During mouse embryonic development, Osr2 expression is first
      detected at E9.25, specifically in the mesonephric vesicles. By E10.0, Osr2
      expression is also observed in the rostro-lateral mandibular mesenchyme
      immediately adjacent to the maxillary processes. In the developing limb buds,
      Osr2 is expressed in a unique mesenchymal domain and the onset of Osr2 expression
      follows a distinct dorsal to ventral developmental time sequence beginning in the
      forelimb and then in the hindlimb. Osr2 exhibits a dynamic expression pattern
      during craniofacial development, in the mandibular and maxillary processes as
      well as the developing palate. Osr2 is also expressed at sites of epithelial
      mesenchymal interactions during tooth and kidney development.

PMID- 11520676
TI  - A 1.8kb GFAP-promoter fragment is active in specific regions of the embryonic
      CNS.
AB  - The intermediate filament glial fibrillary acidic protein (GFAP) constitutes the
      major cytoskeletal protein in astrocytes (J. Neuroimmunol. 8 (1985) 203) and is
      traditionally referred to as a specific marker for astrocytes. To identify early
      glial precursors, we created GFAPpromoter-lacZ transgenic mice, using a 1.8kb 5'
      fragment of human GFAP. The expression of the transgene was first detected in the
      neuroepithelium at embryonic day 9.5. It was further found in the ventricular
      zone of the developing telencephalon, in the cerebellar primordium, trigeminal
      ganglia, and radial glia. Later, scattered beta-gal+ cells were seen in pons,
      brain stem and glia limitans. The results indicate that GFAP activity is
      regulated in a region-specific manner during central nervous system (CNS)
      development and that the gene is turned on in different cell types independently.

PMID- 11520677
TI  - Xenopus Dan, a member of the Dan gene family of BMP antagonists, is expressed in
      derivatives of the cranial and trunk neural crest.
AB  - Dan is the founding member of the Dan family of secreted cytokines. All members
      of this family--which includes Gremlin, Cerberus, Dante, PRDC, and several genes
      identified as expressed sequence tags in the mouse--characterized to date have
      been shown to antagonize signaling by the bone morphogenetic protein (BMP)
      family. During mouse embryogenesis, Dan is expressed in a restricted and dynamic
      pattern. Major sites of transcription include the somites, the myotome and the
      cranial, and facial and limb mesenchyme. Xenopus Dan (XDan) shares over 76% amino
      acid identity with mouse Dan (mDan). Here we report that in Xenopus embryos, XDan
      is expressed both as a maternal transcript and at later stages in populations of
      cells associated with the cranial and trunk neural crest. The conservation of Dan
      expression in cells of the head mesenchyme between Xenopus and mouse embryos
      suggests an important role for BMP antagonists in these tissues.

PMID- 11520678
TI  - Differential gene expression of Xenopus Pitx1, Pitx2b and Pitx2c during cement
      gland, stomodeum and pituitary development.
AB  - The members of the Pitx family of homeobox transcription factors have been
      involved in many aspects of vertebrate embryogenesis, like for example,
      development of teeth, eyes and limbs. We previously reported expression patterns
      and function of Pitx2c in the generation of laterality and asymmetric
      morphogenesis of heart and gastro-intestinal tract in mouse, frog and zebrafish
      (Development 126 (1999) 1225; Mech. Dev. 90 (2000) 41). Here we describe the
      differential expression of Pitx1, Pitx2b and Pitx2c during anterior ectodermal
      pattern formation and differentiation of cement gland, stomodeum and pituitary in
      the frog Xenopus laevis.

PMID- 11520679
TI  - Cloning of a novel retinoic-acid metabolizing cytochrome P450, Cyp26B1, and
      comparative expression analysis with Cyp26A1 during early murine development.
AB  - Tight regulation of retinoic acid (RA) distribution in the embryo is critical for
      normal morphogenesis. The RA-metabolizing enzymes Cyp26A1 and Cyp26B1 are
      believed to play important roles in protecting certain embryonic tissues from
      inappropriate RA signaling. We have cloned the murine Cyp26B1 cDNA and compared
      its expression pattern to that of Cyp26A1 from embryonic day (E) E7-E11.5 using
      in situ hybridization. Northern blot analysis shows the presence of two Cyp26B1
      transcripts of approximately 2.3 and 3.5 kb in embryonic limb bud. Whereas
      Cyp26A1 is expressed in gastrulating embryos by E7, Cyp26B1 is first expressed at
      E8.0 in prospective rhombomeres 3 and 5. Cyp26B1 expression expands to specific
      dorso-ventral locations in rhombomeres 2-6 between E8.5 and E9.5, whereas Cyp26A1
      hindbrain expression is limited to rhombomere 2 at E8.5. No (or very weak)
      Cyp26B1 expression is observed in the tail bud, a major site of Cyp26A1
      expression. Differential expression is seen in branchial arches, with Cyp26A1
      being mainly expressed in neural crest-derived mesenchyme, and Cyp26B1 in
      specific ectodermal and endodermal areas. Cyp26B1 is markedly expressed in the
      ectoderm and distal mesoderm of the limb buds from the beginning of their
      outgrowth. Cyp26A1 transcripts are seen later and at lower levels in limb
      ectoderm, and both transcripts are excluded from the apical ectodermal ridge.

PMID- 11520680
TI  - Foxn4--a new member of the forkhead gene family is expressed in the retina.
AB  - We report the cloning and expression of a novel murine forkhead/winged helix
      family member--Foxn4--that is expressed during neural development in the retina,
      the ventral hindbrain and spinal cord and dorsal midbrain. Retinal Foxn4
      expression is associated with the zone of proliferating progenitor cells. In the
      mouse mutant ocular retardation (or(J)), Foxn4 expression in the retina is
      significantly reduced and terminates prematurely.

PMID- 11520682
TI  - Biochemical and molecular characterization of serine proteases from larvae of
      Chrysomya bezziana, the Old World Screwworm fly.
AB  - The diversity of serine proteases secreted from Chrysomya bezziana larvae was
      investigated biochemically and by PCR and sequence analysis. Cation-exchange
      chromatography of purified larval serine proteases resolved four trypsin-like
      activities and three chymotrypsin-like activities as discerned by kinetic studies
      with benzoyl-Arg-p-nitroanilide and succinyl-Ala-Ala-Pro-Phe-p-nitroanilide.
      Amino-terminal sequencing of the three most abundant fractions gave two
      sequences, which were homologous to other Dipteran trypsins and chymotrypsins.
      Analysis of products generated by PCR of cDNA from whole larvae using specific
      primers based on the amino-terminal sequences and generic serine protease primers
      identified 22 different sequences, while phylogenetic analysis of the deduced
      amino acid sequences differentiated two trypsin-like and four chymotrypsin-like
      families. Phylogenetic comparisons with Dipteran and mammalian serine protease
      sequences showed that all the Chrysomya bezziana sequences clustered with
      Dipteran sequences. The Chrysomya bezziana chymotrypsin-like sequences segregated
      within a Dipteran cluster of chymotrypsin sequences, but were well dispersed
      amongst these sequences. The largest Chrysomya bezziana serine protease family,
      the trypB family, clustered tightly as a group, and was closely related to a
      Lucilia cuprina trypsin but distinct from Drosophila melanogaster alpha and beta
      trypsins. The trypB family contains ten highly homologous sequences and probably
      represents an example of concerted evolution of a trypsin gene in Chrysomya
      bezziana.

PMID- 11520683
TI  - Sequestration, metabolism and partial synthesis of tertiary pyrrolizidine
      alkaloids by the neotropical leaf-beetle Platyphora boucardi.
AB  - Platyphora boucardi leaf-beetles sequester tertiary pyrrolizidine alkaloids of
      the lycopsamine type acquired from their host-plant Prestonia portobellensis
      (Apocynaceae) and synthesize their own alkaloids from exogenous retronecine and
      aliphatic 2-hydroxy acids. Tracer studies with [14C]rinderine and its N-oxide
      revealed that P. boucardi sequesters both alkaloidal forms with the same
      efficiency, but accumulates exclusively tertiary alkaloids. There is no
      substantial alkaloid accumulation in the body outside the defensive glands.
      Feeding studies with [2H][14C]rinderine confirmed that P. boucardi specifically
      epimerizes rinderine to its stereoisomers intermedine and lycopsamine. Feeding
      studies with [2H][14C]retronecine proved the ability of P. boucardi to synthesize
      O7- and O9-(2-hydroxyisovaleryl)-retronecine and O7-lactyl-O9-(2
      hydroxyisovaleryl)-retronecine. Both, alkaloids of the lycopsamine type and self
      synthesized retronecine esters accumulate in the defensive secretions at
      concentrations up to 38 mM and 33 mM, respectively. The different biochemical
      strategies to maintain pro-toxic pyrrolizidine alkaloids and to prevent self
      poisoning, developed by specialized insects, are compared. There are two major
      findings: (1) the chemical defense mediated by plant acquired pyrrolizidine
      alkaloids in the taxonomically related palaearctic Oreina and neotropical
      Platyphora leaf beetles have been evolved independently, since the biochemical
      mechanisms of storing and maintaining the alkaloids is completely different in
      the two genera; (2) unexpected parallels exist between taxonomically unrelated
      Coleoptera and Lepidoptera in their ability to synthesize the same retronecine
      esters and to catalyze the same site-specific epimerizations of the lycopsamine
      stereoisomers.

PMID- 11520684
TI  - Periodic expression of an ecdysteroid-induced nuclear receptor in a lepidopteran
      cell line (IAL-PID2).
AB  - A set of DNA primers was designed within the DNA-binding domain of the Manduca
      hormone receptor 3 (MHR3) cDNA. These primers were used in RT-PCR to isolate a
      204 bp cDNA fragment from IAL-PID2 cells exposed to 10(-6) M 20-hydroxyecdysone
      (20E) for 12 h. The amino acid sequence deduced from the cDNA fragment presented
      100% identity with the zinc finger domain of Manduca hormone receptor 3 (MHR3),
      Galleria hormone receptor 3 (GHR3) and Choristoneura hormone receptor 3 (CHR3).
      This cDNA fragment was used as a probe on total RNA from IAL-PID2 cells exposed
      to 20E and hybridized to mRNA, the size of which was close to 4.5 kb and named
      Plodia hormone receptor 3 (PHR3). Kinetics of induction of PHR3 mRNA were similar
      to that of HR3 genes but varied according to the position of cells in their cell
      cycle. The non-steroidal ecdysone agonist, RH-5992 induced the expression of PHR3
      at lower concentrations than 20E. From sequence similarity, mRNA size, 20E and RH
      5992 inducibilities, we conclude that PHR3 transcript could encode a Plodia
      hormone receptor 3 involved in the genetic signalling cascade of 20E. Thanks to
      its periodic expression, this putative orphan nuclear receptor could serve as a
      suitable cellular marker for studying changes of epidermal cell sensitivity to
      20E during the cell cycle.

PMID- 11520685
TI  - Purification, molecular cloning, and properties of a beta-glycosidase isolated
      from midgut lumen of Tenebrio molitor (Coleoptera) larvae.
AB  - Two beta-glycosidases (M(r) 59k) were purified from midgut contents of larvae of
      the yellow mealworm, Tenebrio molitor (Coleoptera: Tenebrionidae). The two
      enzymes (betaGly1 and betaGly2) have identical kinetic properties, but differ in
      hydrophobicity. The two glycosidases were cloned and their sequences differ by
      only four amino acids. The T. molitor glycosidases are family 1 glycoside
      hydrolases and have the E379 (nucleophile) and E169 (proton donor) as catalytic
      amino acids based on sequence alignments. The enzymes share high homology and
      similarity with other insect, mammalian and plant beta-glycosidases. The two
      enzymes may hydrolyze several substrates, such as disaccharides, arylglucosides,
      natural occurring plant glucosides, alkylglucosides, oligocellodextrins and the
      polymer laminarin. The enzymes have only one catalytic site, as inferred from
      experiments of competition between substrates and sequence alignments. The
      observed inhibition by high concentrations of the plant glucoside amygdalin, used
      as substrate, is an artifact generated by transglucosylation. The active site of
      each purified beta-glycosidase has four subsites, of which subsites +1 and +2
      bind glucose with more affinity. Subsite +2 has more affinity for hydrophobic
      groups, binding with increasing affinities: glucose, mandelonitrile and
      nitrophenyl moieties. Subsite +3 has more affinity for glucose than butylene
      moieties. The intrinsic catalytic constant calculated for hydrolysis of the
      glucose beta-1,4-glucosidic bond is 21.2 s(-1) x M(-1). The putative
      physiological role of these enzymes is the digestion of di- and oligosaccharides
      derived from hemicelluloses.

PMID- 11520686
TI  - 8-O-acetylharpagide is not an ecdysteroid agonist.
AB  - We have reinvestigated the activity of 8-O-acetylharpagide, an iridoid glucoside,
      as an ecdysteroid agonist. Elbrecht et al. (Insect Biochem. Mol. Biol. 26 (1996)
      519) isolated a preparation of this compound from Ajuga reptans L. and ascribed
      ecdysteroid agonist activity on the basis of the induction of an ecdysteroid-like
      response in Drosophila melanogaster KcO cells, the displacement of
      [3H]ponasterone A from the Drosophila receptor and the activation of an
      ecdysteroid-regulated gene in a transactivation assay. We provide evidence that
      the agonist activity derives from contaminating ecdysteroids; A. reptans is a
      species rich in ecdysteroids. Purified 8-O-acetylharpagide is not active in the
      D. melanogaster B(II) cell bioassay, neither as an agonist nor as an antagonist,
      nor does it displace [3H]ponasterone A from dipteran or lepidopteran ecdysteroid
      receptor complexes.

PMID- 11520687
TI  - A conserved domain in arthropod cuticular proteins binds chitin.
AB  - Many insect cuticular proteins include a 35-36 amino acid motif known as the R&R
      consensus. The extensive conservation of this region led to the suggestion that
      it functions to bind chitin. Provocatively, it has no sequence similarity to the
      well-known cysteine-containing chitin-binding domain found in chitinases and some
      peritrophic membrane proteins. Using fusion proteins expressed in E. coli, we
      show that an extended form of the R&R consensus from proteins of hard cuticles is
      necessary and sufficient for chitin binding. Recombinant AGCP2b, a putative
      cuticular protein from the mosquito Anopheles gambiae, was expressed in E. coli
      and the purified protein shown to bind to chitin beads. A stretch of 65 amino
      acids from AGCP2b, including the R&R consensus, conferred chitin binding to
      glutathione-S-transferase (GST). Directed mutagenesis of some conserved amino
      acids within this extended R&R consensus from hard cuticle eliminated chitin
      binding. Thus arthropods have two distinct classes of chitin binding proteins,
      those with the chitin-binding domain found in lectins, chitinases and peritrophic
      membranes (cysCBD) and those with the cuticular protein chitin-binding domain
      (non-cysCBD).

PMID- 11520688
TI  - An acetylcholinesterase purified from the greenbug (Schizaphis graminum) with
      some unique enzymological and pharmacological characteristics.
AB  - An acetylcholinesterase (AChE, EC 3.1.1.7) was purified from the greenbug,
      Schizaphis graminum (Rondani). The maximum velocities (Vmax) for hydrolyzing
      acetylthiocholine (ATC), acetyl-(beta-methyl) thiocholine (AbetaMTC),
      propionylthiocholine, and S-butyrylthiocholine were 78.0, 67.0, 37.4, and 2.3
      micromol/min/mg, and the Michaelis constants (Km) were 57.6, 60.6, 31.3, and 33.4
      microM, respectively. More than 98% of AChE activity was inhibited by 10 microM
      eserine or BW284C51, but only 7% of the activity was inhibited by ethopropazine
      at the same concentration. Based on the substrate and inhibitor specificities,
      the purified enzyme appeared to be a true AChE. Nondenaturing polyacrylamide gel
      electrophoresis (PAGE) and isoelectric focusing of the purified AChE revealed
      three molecular forms. The isoelectric points were 7.3 for the major form and 6.3
      and 7.1 for two minor forms. The major form of purified AChE showed molecular
      masses of 129 kDa for its native protein and 72 kDa for its subunits on SDS-PAGE.
      However, the purified AChE exhibited some distinctive characteristics including:
      (1) lack of affinity to the affinity ligand 3-(carboxyphenyl) ethyldimethyl
      ammonium, which has been used widely in purification of AChE from various insect
      species; and (2) 20-200-fold higher substrate-inhibition thresholds for ATC and
      AbetaMTC than AChE from other insect species. These biochemical properties may
      reflect structural differences of AChE purified from the greenbug compared with
      that from other insect species.

PMID- 11520690
TI  - The shrimp FAMeT cDNA is encoded for a putative enzyme involved in the
      methylfarnesoate (MF) biosynthetic pathway and is temporally expressed in the
      eyestalk of different sexes.
AB  - Methylfarnesoate (MF), an analogue of the insect juvenile hormone III, has been
      implicated to play a vital role in the regulation of the growth and reproductive
      development in crustaceans. Farnesoic acid O-methyltransferase (FAMeT) is the key
      enzyme involved in catalyzing the final step in the MF biosynthetic pathway. In
      this study, we report the cloning and characterization of the cDNA encoding the
      putative FAMeT of the shrimp Metapenaeus ensis. FAMeT comprises 280 amino acid
      residues with a predicted molecular weight of 32kDa. The predicted putative FAMeT
      protein reveals a high degree of structural conservation of FAMeT with the
      lobsters. It shares 79 and 70% sequence identities with the putative FAMeTs of
      Homarus americanus and Panulirus interruptus, respectively. As revealed by the
      Southern blot analysis and genomic PCR, only one gene exists in the shrimp genome
      and the gene is uninterrupted in the coding region. The shrimp FAMeT mRNA is
      widely distributed in many tissues with the highest expression level observed in
      the central nervous system. A constant level of FAMeT expression is recorded in
      the ventral nerve cord of the juveniles and the mature females during the
      reproductive cycle. Unlike the ventral nerve cord, the eyestalk of the juvenile
      male, but not the female, expresses FAMeT. Further study shows that the eyestalk
      of the mature female expresses FAMeT during all stages of ovarian maturation. We
      speculate that FAMeT may be important for the regulation of eyestalk
      neuropeptides. This is the first extensive study on the molecular
      characterization, structural analysis and expression of the crustacean FAMeT.

PMID- 11520689
TI  - Two metal-binding peptides from the insect Orchesella cincta (Collembola) as a
      result of metallothionein cleavage.
AB  - Metallothionein (MT) is an ubiquitous heavy metal-binding protein which has been
      identified in animals, plants, protists, fungi and bacteria. In insects, primary
      structures of MTs are known only for Drosophila and the collembolan, Orchesella
      cincta. The MT cDNA from O. cincta encodes a 77 amino acid protein with 19
      cysteines. Isolations of the protein itself have demonstrated the presence of two
      smaller metal-binding peptides, whose amino acid sequences correspond to parts of
      the cDNA, and which apparently result from cleavage of the native protein. The
      present study was undertaken to complete the picture of cleavage sites within the
      MT protein by applying protein isolation techniques in combination with mass
      spectrometry and N-terminal sequence analysis. Further, recombinant expression
      allowed us to study the intrinsic stability of the MT and to perform in vitro
      cleavage studies. The results show that the MT from O. cincta is specifically
      cleaved at two sites, both after the amino acid sequence Thr-Gln (TQ). One of
      these sites is located in the N-terminal region and the other in the linker
      region between two putative metal-binding clusters. When expressed in Escherichia
      coli, the recombinant O. cincta MT can be isolated in an uncleaved form; however,
      this protein can be cleaved in vitro by the proteolytic activity of O. cincta. In
      combination with other studies, the results suggest that the length of the linker
      region is important for the stability of MT as a two domain metal-binding
      protein.

PMID- 11520692
TI  - Feedback connections and conscious vision.

PMID- 11520691
TI  - Cloning and characterization of a dopachrome conversion enzyme from the yellow
      fever mosquito, Aedes aegypti.
AB  - In this study we describe the purification and molecular cloning of a dopachrome
      conversion enzyme (DCE) from the yellow fever mosquito, Aedes aegypti. DCE
      catalyzes the conversion of L-dopachrome to 5,6-dihydroxyindole in the
      melanization pathway. Melanin biosynthesis is involved with crucial protective
      phenomena in mosquitoes, including egg chorion and cuticular tanning, wound
      healing, and the melanotic encapsulation immune response. The enzyme was purified
      to homogeneity by various chromatographic techniques from A. aegypti larvae and
      has a relative molecular mass of 51 kDa as-revealed by SDS-PAGE analysis.
      Physiochemical analysis of DCE revealed a pH optimum of 7.5-8.0 and substrate
      activity for L-dopachrome and aminochromes generated from dopa methyl ester,
      alpha-methyl dopa and dopamine. Trypsin digestion of the isolated DCE and
      subsequent reverse-phase separation resulted in the isolation of several
      polypeptide fragments, from which two partial internal amino acid sequences were
      obtained by Edman degradation. PCR amplification, using a degenerate primer based
      on one internal amino acid sequence and an oligo-dT primer, produced a 650 bp DNA
      fragment. Subsequent screening of an A. aegypti pupal cDNA library resulted in
      the isolation of a 1.6 kb clone containing coding sequence for both internal DCE
      amino acid sequences, thereby confirming the identity of the isolated gene
      product (pAaDce1) as DCE. Northern analysis revealed the constitutive expression
      of DCE message in developmental stages and adults, with the majority of
      transcript localized in the fat body and ovaries of adult females. AaDce1 mRNA
      increased in abundance above constitutive levels in adult females when a
      melanotic encapsulation immune response was initiated by the intrathoracic
      inoculation of Dirofilaria immitis microfilariae.

PMID- 11520694
TI  - Blinding revelations about rivalry.

PMID- 11520693
TI  - Finding words in a sea of speech.

PMID- 11520696
TI  - Contextual memory in a virtual world.

PMID- 11520695
TI  - At attention and intention.

PMID- 11520697
TI  - The brain as film director.

PMID- 11520699
TI  - Artificial passenger keeps you awake at the wheel.

PMID- 11520698
TI  - The popular face of cognitive science.

PMID- 11520700
TI  - Music to your baby's ears.

PMID- 11520701
TI  - When does action resist visual illusions?
AB  - Over the past decade, many studies of non-pathological individuals have reported
      functional dissociations between perceptual judgments and motor responses. These
      results suggested an interpretation of the ventral and dorsal streams in the
      primate visual system as independent modules for visual awareness and the visual
      guidance of actions. However, recent comparisons of perception and grasping
      responses in size-contrast displays have been widely reported to show that
      apparent dissociations are actually experimental artifacts. An overview of the
      literature suggests that the issue of visuomotor dissociations in healthy
      individuals is far from settled. Some results suggest that immunity from visual
      illusions might be found when task requirements emphasize observer-relative
      reference frames. These results suggest that the functional specialization of the
      two visual subsystems might be less rigid than originally posited.

PMID- 11520702
TI  - Language and perceptual categorisation.
AB  - In a pioneering set of experiments, Rosch investigated the colour processing of a
      remote traditional culture. It was concluded that colours form universally
      natural and salient categories. However, our own cross-cultural research, backed
      up by neuropsychological data and interference studies, indicates that perceptual
      categories are derived from the words in the speaker's language. The new data
      support a rather strong version of the Whorfian view that perceptual categories
      are organized by the linguistic systems of our mind.

PMID- 11520703
TI  - Chimpanzee social cognition.
AB  - In the late 1970s, Premack and Woodruff asked whether chimpanzees had a theory of
      mind. The answer to this question has remained elusive. Whereas some authors
      argue that chimpanzees are capable of mental state attribution, others maintain
      that they simply learn certain cues in ertain situations. Recent studies
      challenge both views. On the one hand, chimpanzees know much more about seeing
      than cue-based explanations suggest; on the other hand, this knowledge does not
      necessarily entail understanding of the mental states of others. The hypothesis I
      put forward here is that chimpanzees learn cues in social situations but that
      they are also capable of knowledge abstraction to solve novel problems.

PMID- 11520704
TI  - Cognitive and neural mechanisms of emotional memory.
AB  - A highly adaptive aspect of human memory is the enhancement of explicit,
      consciously accessible memory for emotional stimuli. Recent findings from
      neuroimaging, neuropsychological, drug and neural stimulation studies indicate
      that emotional stimuli engage specific cognitive and neural mechanisms that
      enhance explicit memory. Emotional arousal influences memory via factors that act
      during memory encoding (attention and elaboration) and factors that modulate
      memory consolidation. Across studies, the amygdala has been consistently
      implicated as playing a key role in enhancing explicit memory for both pleasant
      and unpleasant emotional stimuli through modulation of encoding and consolidation
      processes.

PMID- 11520705
TI  - Telling what we know: describing inner experience.
AB  - It is claimed that psychological science can obtain accurate reports about
      people's inner experience. We reconsider three criticisms of introspection:
      Nisbett and Wilson's critical review of introspection, the failure of
      introspectionists to agree about imageless thought, and Skinner's behavioral
      position. We show that rather than dismissing introspection, these criticisms
      point the way towards technical improvements in the methods used to produce
      accurate descriptions of inner experience. One such method, Descriptive
      Experience Sampling, is described and used as an example to illustrate our
      conclusion that, although exploring inner experience is not trivially easy, it
      can provide important knowledge for many areas in cognitive science.

PMID- 11520706
TI  - Is Chlamydia pneumoniae important in asthma? The first controlled trial of
      therapy leaves the question unanswered.

PMID- 11520707
TI  - Another piece of the inhaled corticosteroids-in-COPD puzzle.

PMID- 11520708
TI  - The air pollution detectives.

PMID- 11520709
TI  - Anticoagulants for acute respiratory distress syndrome: can they work?

PMID- 11520710
TI  - Do inhaled corticosteroids inhibit growth in children?

PMID- 11520711
TI  - Trial of roxithromycin in subjects with asthma and serological evidence of
      infection with Chlamydia pneumoniae.
AB  - An association has been reported between chronic infection with Chlamydia
      pneumoniae and the severity of asthma, and uncontrolled observations have
      suggested that treatment with antibiotics active against C. pneumoniae leads to
      an improvement in asthma control. We studied the effect of roxithromycin in
      subjects with asthma and immunoglobulin G (IgG) antibodies to C. pneumoniae > or
      = 1:64 and/or IgA antibodies > or = 1:16. A total of 232 subjects, from
      Australia, New Zealand, Italy, or Argentina, were randomized to 6 wk of treatment
      with roxithromycin 150 mg twice a day or placebo. At the end of 6 wk, the
      increase from baseline in evening peak expiratory flow (PEF) was 15 L/min with
      roxithromycin and 3 L/min with placebo (p = 0.02). With morning PEF, the increase
      was 14 L/min with roxithromycin and 8 L/min with placebo (NS). In the
      Australasian population, the increase in morning PEF was 18 L/min and 4 L/min,
      respectively (p = 0.04). At 3 mo and 6 mo after the end of treatment, differences
      between the two groups were smaller and not significant. Six weeks of treatment
      with roxithromycin led to improvements in asthma control but the benefit was not
      sustained. Further studies are necessary to determine whether the lack of
      sustained benefit is due to failure to eradicate C. pneumoniae.

PMID- 11520712
TI  - Prevalence of bronchial hyperresponsiveness among HIV-infected men.
AB  - HIV infection is associated with immune dysregulation primarily affecting T-cell
      function, whereas asthma is related to excessive T-cell activity. We compared the
      prevalence of asthma and related conditions among adult seropositive men with the
      prevalence among men of similar age drawn from the general population.
      Seropositive men had a significantly more frequent occurrence of wheezing (54.4
      versus 21.2%), bronchial hyperresponsiveness (BHR) to methacholine (26.2 versus
      14.4%), and an elevated total serum IgE (37.8 versus 25.7%). Differences in BHR
      were significant only among smokers. Among the seropositive men, FEV(1)/FVC and
      an elevated IgE were the principal determinants of BHR. Our results suggest that
      the frequency of asthma may be underestimated in HIV disease. Furthermore, the
      frequent occurrence of BHR in HIV-infected men who smoke (30.1%) suggests this
      group may be especially susceptible to the adverse effects of cigarette smoke.

PMID- 11520713
TI  - Alterations of placental vascular function in asthmatic pregnancies.
AB  - Asthma during pregnancy is associated with low-birthweight neonates at term but
      the mechanisms that cause this outcome are presently unknown. Changes in
      placental vascular function resulting from asthma or its treatment could
      contribute to altered fetal growth. We have prospectively followed women with
      asthma and a control group of women without asthma during their pregnancies,
      classified them based on asthma severity and glucocorticoid intake, and monitored
      fetal development and placental blood flow using Doppler ultrasound at 18 and 30
      wk gestation. The placentae from these women were collected after delivery and
      vascular responses to dilator and constrictor agonists assessed using an in vitro
      placental perfusion method. At 18 wk gestation, umbilical artery flow velocity
      waveforms were significantly reduced in the moderate and severe asthmatic groups
      and in those women using high-dose inhaled glucocorticoid for the treatment of
      their asthma (ANOVA, p < 0.05). However, at 30 wk gestation there were no
      significant differences in umbilical artery flow velocity between control and
      asthmatic women (ANOVA, p > 0.05). Corticotropin-releasing hormone (CRH), a
      potent vasodilator that acts via the nitric oxide pathway, caused a dose
      dependent vasodilatory response in all placentae in vitro. However, CRH-induced
      dilation was significantly reduced in moderate and severe asthmatics (ANOVA, p <
      0.05). Vasoconstrictor responses to potassium chloride and prostaglandin
      F(2alpha) were reduced in placentae from moderate and severe asthmatic women
      (ANOVA, p < 0.05). These studies demonstrate significant differences in placental
      vascular function in pregnancies complicated by asthma, which may relate directly
      to the asthma or be a consequence of the associated glucocorticoid treatment.
      These changes in vascular function in asthmatic pregnancies may contribute to the
      low-birthweight outcome observed in this condition.

PMID- 11520714
TI  - Discriminative capacity of bronchodilator response measured with three different
      lung function techniques in asthmatic and healthy children aged 2 to 5 years.
AB  - The primary aim of this study was to quantify and compare bronchodilator
      responsiveness in healthy and asthmatic children aged 2 to 5 yr. The secondary
      aim of the study was to compare discriminative capacity (i.e., sensitivity,
      specificity, and predictive values of the reversibility test for the diagnosis of
      asthma) for each of the lung function tests applied in the study. Specific airway
      resistance (sRaw) as measured by whole-body plethysmography, respiratory
      resistance as measured with the interrupter technique (Rint), and respiratory
      resistance and reactance at 5 Hz (Rrs5, Xrs5, respectively) as measured with the
      impulse oscillation technique were assessed before and 20 min after inhalation of
      terbutaline from a pressurized metered-dose inhaler via a metal spacer by 92
      children (37 healthy controls and 55 asthmatic subjects). The study of healthy
      children followed a randomized, double-blind, crossover design, whereas the study
      of asthmatic children was open. Baseline lung function was significantly
      decreased in asthmatic children as compared with healthy control subjects as
      reflected by all techniques used in the study. sRaw, Rint, and Rrs5, but not
      Xrs5, improved significantly with terbutaline as compared with placebo in healthy
      control subjects. Lung function improved to a significantly greater extent in
      asthmatic children than in control subjects as reflected by all methods. sRaw
      provided the best discriminative power of such a bronchodilator response, with a
      sensitivity of 66% and specificity of 81% at the cutoff level of a 25% decrease
      in sRaw after bronchodilator administration. In conclusion, bronchodilator
      response measured by sRaw allows a separation of asthmatic from healthy young
      children. This may help define asthma in this clinically difficult-to-manage
      group of young wheezy children. The sensitivity and specificity of the other
      methods used in the study were less than those of sRaw.

PMID- 11520715
TI  - Activated, cytotoxic CD8(+) T lymphocytes contribute to the pathology of asthma
      death.
AB  - This study investigates the presence of CD8(+) T lymphocytes and their possible
      association with viral infection in bronchi of victims of fatal asthma.
      Postmortem samples from the peribronchial region of the lung were obtained from
      seven patients who died an asthma death (AD), seven asthmatic patients who died
      of unrelated causes (AUC), and seven postmortem cases with no history of lung
      disease (control subjects). Using immunohistochemical techniques, the CD8(+)
      cytotoxic T-cell population in peribronchial tissue was characterized in three
      patient groups. The percentage of CD8(+) cells expressing the activation marker
      CD25 was higher in the AD group than in both the AUC and control groups (11.91 +/
      1.92% versus 3.93 +/- 1.63% and 1.09 +/- 0.56%, respectively (p < 0.001).
      Perforin expression, a marker of cytotoxicity, was highest in the AD group (9.16
      +/- 1.5%) compared with 1.39 +/- 0.9; 1.8 +/- 0.6% in the AUC and control groups
      respectively (p < 0.001). Expression of interleukin-4 (IL-4) and interferon gamma
      (IFN-gamma) by CD8(+) T cells was higher in the AD group than the control group
      (p < 0.05). Furthermore, the IFN-gamma/IL-4 ratio in the AD group was less than
      half that of the control group (1.46 +/- 0.2 versus 3.2 +/- 0.1; p = 0.02). Using
      polymerase chain reaction (PCR), viral genome for rhinovirus (RV) was detected in
      lung tissue from three of the seven cases in the AD group. Two of these cases
      also had detectable respiratory syncytial virus (RSV). Viral genome for RSV was
      detected in five of the AUC group and in one of these cases, RV was also
      detected. No viral genome was detected in the lungs of the control group. In
      conclusion, this study provides novel evidence of an aberrant CD8(+) T-cell
      population, possibly in response to viral infection in subjects who die of acute
      asthma.

PMID- 11520716
TI  - Work is related to a substantial portion of adult-onset asthma incidence in the
      Finnish population.
AB  - There are no population-based follow-up studies to estimate the fraction of
      asthma incidence that is attributable to work. In Finland, individuals with
      clinically well-established persistent asthma are registered for reimbursement of
      medication from the national health insurance scheme. We combined, at an
      individual level, these data with the population census data of 1985, 1990, and
      1995 to estimate the attributable fraction of work in adult-onset persistent
      asthma. Our follow-up study covered the entire 25- to 59-yr-old employed
      population of Finland in 1986-1998. Relative risks (RR) for occupational
      categories were estimated in comparison to those employed in administrative work.
      There were 49,575 incident cases of asthma. The attributable fraction of
      occupation was 29% (95% CI 25-33%) for men and 17% (95% CI 15-19%) for women. The
      risk was increased especially in agricultural work, manufacturing work, and
      service work. In addition to already established risk occupations of occupational
      asthma, such as food and beverage work, the analysis identified a large number of
      occupations with significant excess of asthma incidence. The results indicate
      that the impact of occupational factors in the inception of adult-onset
      persistent asthma, and consequently the potential for prevention, is much larger
      and more widely spread than generally assumed.

PMID- 11520717
TI  - Dose-dependent effects of inhaled mometasone furoate on airway function and
      inflammation after allergen inhalation challenge.
AB  - Comparisons of the potency of different inhaled corticosteroids, delivery
      devices, and treatment regimens in the management of asthma can only be made when
      outcome measurements display a dose-dependent effect. These outcomes have been
      difficult to identify. In this study, we compared in a randomized, double-blind,
      crossover design, the effects of 6 d treatment with placebo and three doses (50,
      100, and 400 microg, twice daily) of mometasone furoate delivered by dry powder
      inhaler (MF-DPI) on responses after allergen inhalation challenge. Twelve mild
      asthmatic subjects with dual responses after allergen inhalation were studied.
      Outcome measurements included early and late asthmatic responses, the change in
      methacholine airway responsiveness 24 h after challenge, and sputum eosinophilia
      measured 7 and 24 h after challenge. All three doses of MF-DPI demonstrated
      similar attenuation of early responses and allergen-induced airway
      hyperresponsiveness relative to placebo (p < 0.05). The late maximal %fall in
      FEV(1) after placebo treatment was 23.5% and was significantly reduced in a dose
      dependent manner to 12.3%, 11.0%, and 5.9% for the 50-, 100-, and 400-microg
      twice-daily treatments (p = 0.007). The allergen-induced increase in sputum
      eosinophilia (x10(4) cells/ml) 24 h after challenge during placebo treatment was
      60.2 and was significantly reduced to 24.0, 15.3, and 6.2 for the 50-, 100-, and
      400-microg twice-daily treatments. MF-DPI is effective at attenuating allergen
      induced early and late responses, airway hyperresponsiveness, and sputum
      eosinophilia, and dose-response effects exist for the attenuation of the late
      response.

PMID- 11520718
TI  - The kinetics of allergen-induced eotaxin level in nasal lavage fluid: its key
      role in eosinophil recruitment in nasal mucosa.
AB  - Eotaxin (CCL11) is a potent eosinophil chemoattractant belonging to the C-C
      chemokine. To evaluate the role of eotaxin in eosinophilic inflammation in nasal
      mucosa, we investigated the levels of eosinophil chemoattractants in nasal lavage
      fluids obtained after antigen challenge, compared with eosinophil counts and
      eosinophil protein X (EPX) levels. In subjects with allergic rhinitis, allergen
      challenge led to parallel increases in eosinophil counts, levels of EPX, and
      eotaxin concentrations in nasal lavage fluid. The levels of eotaxin in lavage
      samples showed strong correlation with lavage levels of eosinophil counts and
      EPX. Normal subjects had few, if any, eosinophils and EPX as well as the measured
      parameters in their nasal lavage fluids before and after antigen challenge. In
      our experiments of eosinophil endothelial transmigration (TEM) assay using the
      nasal microvascular endothelial cells, eotaxin showed the most potent effect
      among various eosinophil chemoattractants. In addition, treatment of eosinophils
      with anti-CCR-3 mAb significantly blocked eosinophil TEM induced by homogenate of
      nasal mucosa. These results indicate that eotaxin has an important role in
      eosinophil-dependent inflammation in nasal mucosa and suggest that blocking
      eotaxin or CCR-3 might be useful for new therapeutic tools of allergic rhinitis.

PMID- 11520719
TI  - Inhaled corticosteroids and the risk of mortality and readmission in elderly
      patients with chronic obstructive pulmonary disease.
AB  - There is considerable controversy concerning the utility of inhaled
      corticosteroids for the long-term treatment of patients with COPD. Recent studies
      have suggested that although inhaled corticosteroids do not alter the rate of
      decline in lung function, they may reduce airway hyperresponsiveness, decrease
      the frequency of exacerbations, and slow the rate of decline in the patients'
      health status. The relationship between inhaled corticosteroids and subsequent
      risk of hospitalization or mortality remains unknown. We therefore conducted a
      population-based cohort study using administrative databases in Ontario, Canada
      (n = 22,620) to determine the association between inhaled corticosteroid therapy
      and the combined risk of repeat hospitalization and all-cause mortality in
      elderly patients with COPD. Patients who received inhaled corticosteroid therapy
      postdischarge (within 90 d) had 24% fewer repeat hospitalizations for COPD (95%
      confidence interval [CI], 22 to 35%) and were 29% less likely to experience
      mortality (95% CI, 22 to 35%) during 1 yr of follow-up after adjustment for
      various confounding factors. This cohort study has suggested that inhaled
      corticosteroid therapy is associated with reduced COPD-related morbidity and
      mortality in elderly patients. Although not definitive, because of the
      observational nature of these findings, these data provide a compelling rationale
      for a large randomized trial to determine the effect of inhaled corticosteroids
      on COPD-related morbidity and mortality.

PMID- 11520720
TI  - Relationship between extent of pulmonary emphysema by high-resolution computed
      tomography and lung elastic recoil in patients with chronic obstructive pulmonary
      disease.
AB  - We investigated the relationship between the extent of pulmonary emphysema,
      assessed by quantitative high-resolution computed tomography (HRCT), and lung
      mechanics in 24 patients with chronic obstructive pulmonary disease (COPD). The
      extent of emphysema was quantified as the relative lung area with CT numbers < 
      950 Hounsfield Units (HU). Patients with COPD had severe airflow obstruction
      (FEV(1) 35 +/- 15% pred) and severe reduction of CO diffusion constant (DCO/VA 37
      +/- 19% pred). Maximal static elastic recoil pressure (Pst(max)) averaged 54 +/-
      24% predicted, and the exponential constant K of pressure-volume curves was 258
      +/- 116% predicted. Relative lung area with CT numbers < -950 HU averaged 21 +/-
      11% (range 1 to 38%). It showed a highly significant negative correlation with
      DCO/VA (r = -0.84, p < 0.0001), a weak correlation with FEV(1)% predicted, and no
      correlation with either Pst(max) or constant K. A significant relationship was
      found between the natural logarithm of K and the full width at half maximum of
      the frequency distribution of CT numbers, taken as an index of the heterogeneity
      of lung density (r = 0.68, p < 0.0005). We conclude that currently used methods
      of assessing the extent of emphysema by HRCT closely reflect the reduction of CO
      diffusion constant, but cannot predict the elastic properties of the lung tissue.

PMID- 11520721
TI  - The impact of aging and smoking on the future burden of chronic obstructive
      pulmonary disease: a model analysis in the Netherlands.
AB  - Chronic obstructive pulmonary disease (COPD) causes extensive disability,
      primarily among the elderly. On the World Health Organization ranking list of
      disability-adjusted life years (DALYs), COPD rises from the twelfth to the fifth
      place from 1990 to 2020. The purpose of this study is to single out the impact of
      changes in demography and in smoking behavior on COPD morbidity, mortality, and
      health care costs. A dynamic multistate life table model was used to compute
      projections for the Netherlands. Changes in the size and composition of the
      population cause COPD prevalence to increase from 21/1,000 in 1994 to 33/1,000 in
      2015 for men, and from 10/ 1,000 to 23/1,000 for women. Changes in smoking
      behavior reduce the projected prevalence to 29/1,000 for men, but increase it to
      25/ 1,000 for women. Total life years lost increase more than 60%, and DALYs lost
      increase 75%. Costs rise 90%; smokers cause approximately 90% of these costs. The
      model demonstrates the unavoidable increase in the burden of COPD, an increase
      that is larger for women than for men. The major causes of this increase are past
      smoking behavior and the aging of the population; changes in smoking behavior
      will have only a small effect in the nearby future.

PMID- 11520722
TI  - Marked sympathetic activation in patients with chronic respiratory failure.
AB  - The autonomic nervous system may be disturbed in chronic respiratory failure. We
      tested the hypothesis that there is increased sympathetic activity in patients
      with chronic hypoxemia. Furthermore, we examined the effect of short-term oxygen
      on muscle sympathetic nerve activity (MSNA) in these patients. We performed
      microneurography of the peroneal nerve in 11 patients with hypoxemia due to
      chronic obstructive pulmonary disease (COPD, n = 6) or lung fibrosis (n = 5) and
      in 11 healthy subjects matched for age and sex. MSNA was measured during normal
      breathing in all subjects. In eight patients and in seven control subjects, MSNA
      was also measured during nasal oxygen (4 L/min). MSNA was higher in the patients
      with chronic respiratory failure compared with the healthy subjects during normal
      breathing (61 +/- 5 versus 34 +/- 2 bursts/min, mean +/- SEM; p = 0.0002, paired
      t test). During oxygen administration, MSNA decreased from 63 +/- 6 to 56 +/- 6
      bursts/min in the patients (p = 0.0004, ANOVA); there was no change in
      sympathetic activity in the control subjects. For the first time, there is direct
      evidence of marked sympathetic activation in patients with chronic respiratory
      failure. This is partly explained by arterial chemoreflex activation and may play
      an important role in the pathogenesis of the disease.

PMID- 11520723
TI  - Tumor necrosis factor receptor 2 contributes to ozone-induced airway
      hyperresponsiveness in mice.
AB  - The purpose of this study was to determine whether tumor necrosis factor (TNF)
      contributes to airway hyperresponsiveness (AHR) and migration of
      polymorphonuclear leukocytes (PMN) into the airways following exposure to ozone
      (O(3)). Wild-type mice, TNF p55 or p75 receptor knockout mice (p55 TNFR -/- and
      p75 TNFR -/-), as well as double receptor knockout mice (p55/p75 TNFR -/-), were
      exposed to O(3). Three hours after cessation of O(3), airway responses to inhaled
      methacholine were determined by whole body plethysmography using changes in
      enhanced pause (Penh) as an index of airway narrowing. In wild-type mice, O(3)
      exposure (0.5 ppm, 3 h) caused a significant increase in airway responsiveness as
      indicated by a 1.2 log leftward shift in the methacholine dose- response curve.
      In contrast, in p55/p75 TNFR -/- mice, O(3) caused only a 0.5 log shift in the
      dose-response curve (p < 0.05 compared with wild-type). Similar results were
      obtained in p75 TNFR -/- mice. In contrast, O(3)-induced airway
      hyperresponsiveness was not different in WT and p55 TNFR -/- mice. During O(3)
      exposure (1 pm, 3 h), minute ventilation (V E) decreased by 64 +/- 4% in wild
      type, but only 24 +/- 5% in p55/p75 TNFR -/- mice, indicating that despite their
      reduced O(3)-induced AHR, the TNFR-deficient mice actually inhaled a greater dose
      of O(3). Similar results were obtained in p75 -/- mice, whereas changes in V E
      induced by O(3) were the same in wild-type and p55 -/- mice. PMN numbers in
      bronchoalveolar lavage fluid recovered 21 h after cessation of exposure to O(3)
      (2 ppm, 3 h) were significantly increased compared with after air exposure but
      were not different in wild-type and p55/p75 TNFR -/- mice. Our results indicate
      that TNF contributes to the AHR but not the PMN emigration induced by acute O(3)
      exposure. KEYWORDS: whole body plethysmography; polymorphonuclear leukocytes;
      minute ventilation; knockout mice; methacholine

PMID- 11520724
TI  - Effectiveness of CPAP treatment in daytime function in sleep apnea syndrome: a
      randomized controlled study with an optimized placebo.
AB  - Application of continuous positive airway pressure (CPAP) as the standard
      treatment for sleep apnea/hypopnea syndrome (SAHS) is a moot point. Studies on
      the effectiveness of this treatment have been challenged because of the lack of a
      suitable placebo. The recent description of a true placebo (sham CPAP) prompted
      us to conduct a randomized trial of CPAP or placebo to assess the effectiveness
      of CPAP in improving SAHS-related symptoms and daytime function in patients with
      moderate to severe SAHS. Forty-eight patients, stratified in four groups
      according to severity, were randomly allocated into two treatment groups (optimal
      and sham CPAP) for a 6-wk period. Of these, 45 completed follow-up (91% males;
      age: 54 +/- 10 yr; body mass index [BMI]: 32 +/- 6 kg/m(2); apnea-hypopnea index
      [AHI]: 54 +/- 19 events/h; and Epworth Sleepiness Scale [ESS]: 16 +/- 5). The
      ESS, a questionnaire on SAHS-related symptoms, Functional Outcomes Sleep
      Questionnaire (FOSQ), and the Short Form Health Survey (SF-36) were completed at
      inclusion and after treatment. After 10 d of washout, the placebo group was
      treated with optimal CPAP and reassessed before and after optimal CPAP. The group
      receiving optimal CPAP when compared with the group with sham CPAP showed
      considerably greater improvement in the relief of sleepiness (-9.5 versus -2.3, p
      < 0.001), other SAHS-related symptoms (-18.5 versus -4.5, p < 0.001), vigilance
      (+8.5 versus +3.4, p = 0.009), and general productivity (+4.0 versus +0.5, p =
      0.04) FOSQ scales. Both groups used a similar number of hours for the optimal and
      the sham CPAP (4.3 versus 4.5, (p = NS). The patients initially treated with
      placebo CPAP improved significantly more when optimal CPAP was applied for ESS (
      2.3 versus -6.7, p < 0.001) and other sleep apnea syndrome (SAS)-related symptoms
      (-4.5 versus -11.2, p = 0.02). Our study provides strong evidence of the
      effectiveness of CPAP treatment in improving symptoms and perceived health status
      in moderate to severe SAHS.

PMID- 11520725
TI  - Adaptive pressure support servo-ventilation: a novel treatment for Cheyne-Stokes
      respiration in heart failure.
AB  - Adaptive servo-ventilation (ASV) is a novel method of ventilatory support
      designed for Cheyne-Stokes respiration (CSR) in heart failure. The aim of our
      study was to compare the effect of one night of ASV on sleep and breathing with
      the effect of other treatments. Fourteen subjects with stable cardiac failure and
      receiving optimal medical treatment were tested untreated and on four treatment
      nights in random order: nasal oxygen (2 L/min), continuous positive airway
      pressure (CPAP) (mean 9.25 cm H(2)O), bilevel (mean 13.5/5.2 cm H(2)O), or ASV
      largely at the default settings (mean pressure 7 to 9 cm H(2)O) during
      polysomnography. Thermistor apnea + hypopnea index (AHI) declined from 44.5 +/-
      3.4/h (SEM) untreated to 28.2 +/- 3.4/h oxygen and 26.8 +/- 4.6/h CPAP (both p <
      0.001 versus control), 14.8 +/- 2.3/h bilevel, and 6.3 +/- 0.9/h ASV (p < 0.001
      versus bilevel). Effort band AHI behaved similarly. Arousal index decreased from
      65.1 +/- 3.9/h untreated to 29.8 +/- 2.8/h oxygen and 29.9 +/- 3.2/h CPAP, to
      16.0 +/- 1.3/h bilevel and 14.7 +/- 1.8/h ASV (p < 0.01 versus all except
      bilevel). There were large increases in slow-wave and rapid eye movement (REM)
      sleep with ASV but not with oxygen or CPAP. All subjects preferred ASV to CPAP.
      One night ASV suppresses central sleep apnea and/or CSR (CSA/CSR) in heart
      failure and improves sleep quality better than CPAP or 2 L/min oxygen.

PMID- 11520726
TI  - Effect of endotoxin on ventilation and breath variability: role of cyclooxygenase
      pathway.
AB  - To evaluate the effects of endotoxemia on respiratory controller function, 12
      subjects were randomized to receive endotoxin or saline; six also received
      ibuprofen, a cyclooxygenase inhibitor, and six received placebo. Administration
      of endotoxin produced fever, increased respiratory frequency, decreased
      inspiratory time, and widened alveolar-arterial oxygen tension gradient (all p <
      or = 0.001); these responses were blocked by ibuprofen. Independent of ibuprofen,
      endotoxin produced dyspnea, and it increased fractional inspiratory time, minute
      ventilation, and mean inspiratory flow (all p < or = 0.025). Endotoxin altered
      the autocorrelative behavior of respiratory frequency by increasing its
      autocorrelation coefficient at a lag of one breath, the number of breath lags
      with significant serial correlations, and its correlated fraction (all p < 0.05);
      these responses were blocked by ibuprofen. Changes in correlated behavior of
      respiratory frequency were related to changes in arterial carbon dioxide tension
      (r = 0.86; p < 0.03). Endotoxin decreased the oscillatory fraction of inspiratory
      time in both the placebo (p < 0.05) and ibuprofen groups (p = 0.06). In
      conclusion, endotoxin produced increases in respiratory motor output and dyspnea
      independent of fever and symptoms, and it curtailed the freedom to vary
      respiratory timing-a response that appears to be mediated by the cyclooxygenase
      pathway.

PMID- 11520727
TI  - Significance of the changes in the respiratory system pressure-volume curve
      during acute lung injury in rats.
AB  - The hypothesis that the changes in the respiratory system pressure- volume (PV)
      curve during pulmonary edema mainly reflect distal airway obstruction was
      investigated in rats. Normal rats had a well-defined upper inflection point (UIP)
      at low airway pressure. Airway occlusion by liquid instillation decreased
      compliance (Crs) and the volume (Vuip) of the UIP, and increased end-inspiratory
      pressure. The same changes were observed during the progression of edema produced
      by high volume ventilation (HV). Changes in Vuip and in Crs produced by HV were
      correlated with edema severity in normal rats or rats with lungs preinjured with
      alpha-naphthylthiourea. Vuip and Crs changes were proportional, reflecting
      compression of the PV curve on the volume axis and suggesting reduction of the
      amount of ventilatable lung at low airway pressure. In keeping with this
      explanation, the lower Vuip and Crs were before HV, the more severe HV-induced
      edema was in alpha-naphthylthiourea-injected rats. When edema was profuse, PV
      curves displayed a marked lower inflection point (LIP), the UIP at low pressure
      disappeared but another was seen at high volume above the LIP, and the
      correlation between Vuip changes and edema severity was lost. These observations
      may have clinical relevance in the context of the "open lung" strategy. KEYWORDS:
      ventilator-induced lung injury; respiratory mechanics; acute respiratory distress
      syndrome

PMID- 11520728
TI  - Helium-oxygen in the postextubation period decreases inspiratory effort.
AB  - After tracheal extubation, upper and total airway resistances may frequently be
      increased resulting in an increase in inspiratory effort to breathe. We tested
      whether breathing a helium-oxygen mixture (HeO(2)) would reduce inspiratory
      effort in the period after extubation. Eighteen consecutive patients with no
      chronic obstructive pulmonary disease who had received mechanical ventilation (>
      48 h) were successively studied immediately after extubation (N(2)O(2)), 15 min
      after breathing HeO(2), and after return to N(2)O(2). Effort to breathe, assessed
      by the transdiaphragmatic pressure swings (DeltaPdi) and the pressure-time index
      of the diaphragm (PTI), comfort, and gas exchange, were the main end points. The
      mean reduction of the transdiaphragmatic pressure under HeO(2) was 19 +/- 5%. All
      but three patients presented a decrease in transdiaphragmatic pressure under
      HeO(2), ranging from - 4 to - 55%, and a significant reduction in DeltaPdi was
      observed between HeO(2) and N(2)O(2) (10.2 +/- 0.7 versus 8.6 +/- 1.1 versus 10.0
      +/- 0.8 cm H(2)O for the three consecutive periods; p < 0.05). PTI also differed
      significantly between HeO(2) and N(2)O(2) (197 +/- 19 versus 166 +/- 22 versus
      201 +/- 23 cm H(2)O/s/min for the three periods; p < 0.05). Breathing HeO(2)
      significantly improved comfort, whereas gas exchange was not modified. We
      conclude that the use of HeO(2) in the immediate postextubation period decreases
      inspiratory effort and improves comfort.

PMID- 11520729
TI  - Physiological response to pressure support ventilation delivered before and after
      extubation in patients not capable of totally spontaneous autonomous breathing.
AB  - We designed a prospective, physiological study in 12 patients affected by chronic
      respiratory disorders. The study was aimed at assessing the diaphragm energy
      expenditure (PTPdi), lung resistance (RL) and elastance (EL), arterial blood
      gases (ABG), breathing pattern, and dyspnea measured by a visual analog scale
      during invasive pressure support ventilation (i-PSV) and noninvasive PSV (n-PSV).
      The ventilator settings were kept the same. Both i-PSV and n-PSV significantly
      reduced the PTPdi per minute, compared with that during a T-piece trial (204.4 +/
      93.8 cm H(2)O x s/min [i-PSV]; 197.5 +/- 119.8 [n-PSV]; 393.8 +/- 129.0 [T
      piece]). Expired tidal volume (VTe) was significantly higher (p < 0.05) during n
      PSV (615 +/- 166 ml) than during i-PSV (519 +/- 140 ml). The respiratory pump
      (PTPdi/VTe) was more effective (p < 0.05) with noninvasive ventilation (22.3 +/-
      2.3 cm H(2)O x s/L for i-PSV versus 17.2 +/- 3.3 for n-PSV). RL and EL were
      similar with the two modes of ventilation. Overall dyspnea was significantly (p <
      0.05) better during n-PSV than i-PSV, whereas ABG were similar. We have shown, in
      patients affected by stable chronic respiratory disorders not ready to sustain
      totally spontaneous breathing, that i-PSV and n-PSV are equally effective in
      reducing the PTPdi and in improving ABG, but that n-PSV seems to be better
      tolerated.

PMID- 11520730
TI  - Application of tracheal gas insufflation to acute unilateral lung injury in an
      experimental model.
AB  - In unilateral lung injury, application of global positive end-expiratory pressure
      (PEEP) may cause overdistension of normal alveoli and redistribution of blood
      flow to diseased lung areas, thereby worsening oxygenation. We hypothesized that
      selective application of tracheal gas insufflation (TGI) will recruit the injured
      lung without causing overdistension of the normal lung. In eight anesthetized
      dogs, left lung saline lavage was performed until Pa(O(2))/FI(O(2)) fell below
      100 mm Hg. Then, the dogs were reintubated with a Univent single lumen
      endotracheal tube that incorporates an internal catheter to provide TGI. After
      injury, increasing PEEP from 3 to 10 cm H(2)O did not change gas exchange,
      hemodynamics, or lung compliance. Selective TGI, while keeping end-expiratory
      lung volume (EELV) constant, improved Pa(O(2))/FI(O(2)) from 212 +/- 43 to 301 +/
      38 mm Hg (p < 0.01) while Pa(CO(2)) and airway pressures decreased (p < 0.01).
      During selective TGI, reducing tidal volume to 5.2 ml/kg while keeping EELV
      constant, normalized Pa(CO(2)), did not affect Pa(O(2))/FI(O(2)), and decreased
      end-inspiratory plateau pressure from 16.6 +/- 1.0 to 11.9 +/- 0.5 cm H(2)O (p <
      0.01). In unilateral lung injury, we conclude that selective TGI (1) improves
      oxygenation at a lower pressure cost as compared with conventional mechanical
      ventilation, (2) allows reduction in tidal volume without a change in alveolar
      ventilation, and (3) may be a useful adjunct to limit ventilator-associated lung
      injury.

PMID- 11520731
TI  - Elevated plasma surfactant protein-B predicts development of acute respiratory
      distress syndrome in patients with acute respiratory failure.
AB  - Surfactant protein-B is a lung specific protein secreted into the air spaces by
      pulmonary epithelial type II cells that leaks into the bloodstream in increased
      amounts in patients with ARDS. To test whether elevated plasma levels of
      surfactant protein-B would predict the development of ARDS in patients with acute
      hypoxemic respiratory failure, plasma and lung injury scores were collected at
      study entry and daily thereafter for 3 d from 54 patients admitted to our
      intensive care unit. ARDS was defined as a new bilateral infiltrate on chest
      radiograph and a lung injury score > or = 2.5. Twenty patients developed ARDS, of
      whom seven died. Although the initial lung injury score was not predictive of
      ARDS, the initial plasma surfactant protein-B was predictive (area under the
      curve = 0.77 [0.63 to 0.90], nonparametric receiver-operating characteristic
      analysis). In this cohort, plasma surfactant protein-B was particularly
      predictive of ARDS when applied to patients suffering a direct lung insult (area
      under the curve = 0.87 [0.72 to 1.02]), with a sensitivity of 85% (95% CI: 55 to
      98%) and specificity of 78% (40 to 97%) at a cutoff of 4,994 ng/ml.

PMID- 11520732
TI  - Prediction of psychiatric morbidity in severely injured accident victims at one
      year follow-up.
AB  - The objective of this study was to assess the prevalence of posttraumatic stress
      disorder (PTSD) and symptoms of depression and anxiety in severely injured
      accident victims 1 yr posttrauma and to predict psychiatric morbidity by means of
      variables assessed shortly after the accident. The sample consisted of 106
      consecutive patients with accidental injuries (mean Injury Severity Score = 21.9,
      mean Glasgow Coma Scale score = 14.4) admitted to the intensive care unit of a
      University Hospital. Patients with severe head injuries, suicide attempters, and
      victims of physical assault were excluded. At 1-yr follow-up, two patients (1.9%)
      had PTSD, and 13 (12.3%) had subsyndromal PTSD. Eighteen patients (17%) had
      clinically relevant symptoms of anxiety, and nine (8.5%) were depressed. Overall,
      27 patients (25.5%) showed some form of psychiatric morbidity (full or
      subsyndromal PTSD and/or anxiety and/or depression). Logistic regression
      analysis, using 1-yr psychiatric morbidity status as the dependent variable,
      allowed correct classification of 83.8% of patients 12 mo postaccident
      (specificity 91.8%, sensitivity 61.5%). Biographical risk factors and a sense of
      death threat contributed significantly to the predictive model. We conclude that
      a substantial proportion of severely injured accident victims develop some form
      of psychiatric morbidity that can be predicted to some degree by mainly
      psychosocial variables.

PMID- 11520733
TI  - Percutaneous pulmonary artery and vein stenting: a novel treatment for
      mediastinal fibrosis.
AB  - Mediastinal fibrosis is a rare consequence of infection with the fungus
      Histoplasma capsulatum that can lead to occlusion of large pulmonary arteries and
      veins and mainstem bronchi. Medical and surgical treatments for this disorder
      have been ineffective. We describe successful treatment for central pulmonary
      arterial and venous obstruction due to mediastinal fibrosis in four patients
      using percutaneously placed intravascular stents. Patients were severely limited,
      World Health Organization functional class III or IV. At the time of right and
      left heart catheterization, stents were placed in pulmonary arteries (n = 1),
      veins (n = 2), or both (n = 1) to relieve vascular obstruction resulting from
      mediastinal fibrosis. Immediate hemodynamic and clinical improvement was observed
      in all patients. Three of the four patients have had sustained improvement in
      exercise tolerance, from 3.5 mo to 4.5 yr after stent placement. The only
      complication was a self-limited pulmonary hemorrhage in one patient. Our initial
      experience suggests that percutaneous stent placement to relieve central
      pulmonary arterial or venous obstruction due to mediastinal fibrosis is an
      effective new treatment modality.

PMID- 11520734
TI  - Mutational and radiographic analysis of pulmonary disease consistent with
      lymphangioleiomyomatosis and micronodular pneumocyte hyperplasia in women with
      tuberous sclerosis.
AB  - Lymphangioleiomyomatosis (LAM) and multifocal micronodular pneumocyte hyperplasia
      (MMPH) produce cystic and nodular disease, respectively, in the lungs of patients
      with tuberous sclerosis. The objective of this study was to prospectively
      characterize the prevalence, clinical presentation, and genetic basis of lung
      disease in TSC. We performed genotyping and computerized tomographic (CT)
      scanning of the chest on 23 asymptomatic women with tuberous sclerosis complex
      (TSC). Cystic pulmonary parenchymal changes consistent with LAM were found in
      nine patients (39%). These patients tended to be older than cyst-negative
      patients (31.9 +/- 7.6 yr versus 24.8 +/- 11.6 yr, p = 0.09). There was no
      correlation between presence of cysts and tobacco use, age at menarche, history
      of pregnancy, or estrogen-containing medications. Three of the cyst-positive
      patients had a prior history of pneumothorax. Pulmonary function studies revealed
      evidence of gas trapping but normal spirometric indices in the cyst-positive
      group. All nine cyst-positive patients had angiomyolipomas (AML), which were
      larger (p < 0.05) and more frequently required intervention (p = 0.08) than cyst
      negative patients (8 of 14 with AMLs, p < 0.05). Ten patients (43%) had pulmonary
      parenchymal nodules. Pulmonary nodules were more common in women with cysts (78%
      versus 21%, p < 0.05), and 52% of all patients had either cystic or nodular
      changes. TSC2 mutations were identified in all cyst-positive patients who were
      tested (n = 8), whereas both TSC1 and TSC2 mutations were found in patients with
      nodular disease. Correlation of the mutational and radiographic data revealed one
      pair of sisters who were discordant for cystic disease, two mother- daughter
      pairs who were discordant for nodular disease, and no clear association between
      cyst development and a specific mutational type. This prospective analysis
      demonstrates that cystic and nodular pulmonary changes consistent with LAM and
      MMPH are common in women with TSC.

PMID- 11520735
TI  - Prevalence and clinical characteristics of lymphangioleiomyomatosis (LAM) in
      patients with tuberous sclerosis complex.
AB  - The true prevalence of pulmonary lymphangioleiomyomatosis (LAM) in patients with
      tuberous sclerosis complex (TSC) is unknown. The prevalence of LAM, radiological
      features, and lung function in patients with TSC was measured. The presence of
      LAM, as defined by the presence of cysts by high-resolution chest computed
      tomography (HRCT) scan, was determined in patients with TSC without prior
      pulmonary disease (Group 1). To determine the significance of early detection,
      severity of disease in screened patients (Group 1) was compared with that in
      patients with TSC with a prior diagnosis of LAM (Group 2). Forty-eight patients
      with TSC and no prior history of LAM were screened. Of the 38 females, 13 (34%)
      had LAM; LAM was absent in males. Lung function was preserved in patients with
      TSC who were found to have LAM by screening. In patients previously known to have
      LAM, FEV(1) and DL(CO) correlated inversely with severity of disease as assessed
      by CT scan. The prevalence of LAM in women with TSC was 34%, approximately 10
      fold that previously reported, consistent with a large hitherto unrecognized
      subclinical population of patients at risk for pulmonary complications.

PMID- 11520736
TI  - Prevention of cytomegalovirus infection-enhanced experimental obliterative
      bronchiolitis by antiviral prophylaxis or immunosuppression in rat tracheal
      allografts.
AB  - In this study, the prevention of rat cytomegalovirus (RCMV) infection-enhanced
      experimental obliterative bronchiolitis in rat tracheal allografts was
      investigated. RCMV infection markedly enhanced cell proliferation and
      histological changes of obliterative bronchiolitis, a form of chronic rejection
      after lung transplantation. These alterations were linked to increased
      interleukin (IL)-2 and tumor necrosis factor-alpha (TNF-alpha) immunoreactivity,
      and reduction of IL-10 expression. In recipient rats with acute RCMV infection,
      prophylaxis with either ganciclovir (DHPG) or hyperimmune serum (HIS) totally
      prevented RCMV infection-enhanced tracheal occlusion. DHPG treatment initiated
      during acute RCMV infection also reduced lesion development but markedly less
      than DHPG prophylaxis. Treatment of acute RCMV infection with HIS alone or in
      combination with DHPG had no significant effect on tracheal occlusion. Inhibition
      of the transcription of cytokines by high doses of cyclosporine A significantly
      reduced RCMV infection-enhanced tracheal obliteration. In rats with chronic RCMV
      infection, obliterative alterations were prevented by DHPG prophylaxis initiated
      at the time of transplantation. Prophylaxis either with DHPG or HIS did not
      affect the amount of infectious RCMV recovered from host salivary glands, nor
      were there differences seen in RCMV major immediate early DNA expression in
      tracheal allografts between different antiviral drug regimens.
      Immunohistochemical analysis of allografts revealed that inhibition of tracheal
      occlusion by antiviral prophylaxis was associated with a reduction in the number
      of ED1(+) macrophages and cells staining for Th1 cytokines and TNF-alpha, while
      immune modulation by cyclosporine A up-regulated IL-10 production. In conclusion,
      the results of the present study suggest that the CMV infection-enhanced chronic
      rejection develops independently of viral load but requires both immune
      activation and simultaneous CMV gene expression beyond immediate early genes.

PMID- 11520737
TI  - Role of CD4(+) CD25(+) regulatory T cells in T helper 2 cell-mediated allergic
      inflammation in the airways.
AB  - It has recently been shown that CD4(+) CD25(+) T cells are immunoregulatory T
      cells that prevent CD4(+) T cell-mediated organ-specific autoimmune diseases. To
      determine whether CD4(+) CD25(+) T cells downregulate Th2 cell-mediated allergic
      inflammation in the airways, we studied antigen-induced eosinophil recruitment in
      the airways in BALB/c Rag-2(-)(/-) mice transferred with CD4(+) CD25(+) T cell
      depleted or unfractionated T cells from ovalbumin-specific TCR transgenic mice.
      Antigen-induced eosinophil recruitment into the airways was significantly
      decreased in the mice transferred with CD4(+) CD25(+) T cell-depleted splenocytes
      as compared with those transferred with unfractionated splenocytes. On the other
      hand, the depletion of CD4(+) CD25(+) T cells increased antigen-induced
      neutrophil and T cell recruitment in the airways of the mice. The depletion of
      CD4(+) CD25(+) T cells also decreased antigen-induced IL-4 and IL-5 production in
      the airways of the mice. Finally, the depletion of CD4(+) CD25(+) T cells
      prevented antigen-induced Th2 cell differentiation in vitro but increased the
      differentiation of Th1 cells. These results indicate that CD4(+) CD25(+) T cells
      modulate the Th1 and Th2 cell balance toward Th2 cells and thus upregulate Th2
      cell-mediated allergic inflammation in the airways.

PMID- 11520739
TI  - Magnetic resonance imaging of the upper airway structure of children with
      obstructive sleep apnea syndrome.
AB  - The anatomical relationships between lymphoid, bony, and other tissues affecting
      the shape of the upper airway in children with obstructive sleep apnea syndrome
      (OSAS) have not been established. We therefore compared the upper airway
      structure in 18 young children with OSAS (age 4.8 +/- 2.1 yr; 12 males and 6
      females) and an apnea index of 4.3 +/- 3.9, with 18 matched control subjects
      (age, 4.9 +/- 2.0 yr; 12 males and 6 females). All subjects underwent magnetic
      resonance imaging under sedation. Axial and sagittal T1- and T2-weighted
      sequences were obtained. Images were analyzed with image-processing software to
      obtain linear, area, and volumetric measurements of the upper airway and the
      tissues comprising the airway. The volume of the upper airway was smaller in
      subjects with OSAS in comparison with control subjects (1.5 +/- 0.8 versus 2.5 +/
      1.2 cm(3); p < 0.005) and the adenoid and tonsils were larger (9.9 +/- 3.9 and
      9.1 +/- 2.9 cm(3) versus 6.4 +/- 2.3 and 5.8 +/- 2.2 cm(3); p < 0.005 and p <
      0.0005, respectively). Volumes of the mandible and tongue were similar in both
      groups; however, the soft palate was larger in subjects with OSAS (3.5 +/- 1.1
      versus 2.7 +/- 1.2 cm(3); p < 0.05). We conclude that in children with moderate
      OSAS, the upper airway is restricted both by the adenoid and tonsils; however,
      the soft palate is also larger in this group, adding further restriction.

PMID- 11520738
TI  - Inhibitors of mitogen-activated protein kinases differentially regulate
      eosinophil-activating cytokine release from human airway smooth muscle.
AB  - Airway smooth muscle (ASM) is a potential source of multiple proinflammatory
      cytokines during airway inflammation. In the present study, we examined a
      requirement for mitogen-activated protein (MAP) kinase activation for interleukin
      (IL)-1beta-stimulated GM-CSF, RANTES, and eotaxin release. IL-1beta induced
      concentration-dependent phosphorylation of p42/p44 extracellular signal-regulated
      kinases (ERKs), p38 MAP kinase, and c-Jun amino-terminal kinase (SAPK/JNK).
      p42/p44 ERK and p38 MAP kinase phosphorylation peaked at 15 min and remained
      elevated up to 4 h. SAPK/JNK phosphorylation also peaked at 15 min but fell to
      baseline within 60 min. SB 203580 selectively inhibited IL-1beta-stimulated
      activation of p38 MAP kinase; U 0126 was selective against p42/p44 ERK activity.
      SB 202474, an inactive analog, had no effect on p42/p44 ERK, p38 MAP kinase, or
      SAPK/JNK activation, or on eotaxin or RANTES release. Eotaxin release was
      inhibited by SB 203580 and U 0126, whereas RANTES release was prevented by U 0126
      only. GM-CSF release was inhibited by U 0126 but enhanced by SB 203580. These
      data indicate that RANTES release is dependent on p42/p44 ERK activation but
      occurs independently of p38 MAP kinase activity. Eotaxin release, however, is
      dependent on both p38 MAP kinase- and p42/p44 ERK-dependent mechanisms. GM-CSF
      release is p42/p44 ERK dependent and is tonically suppressed by a mechanism that
      is partially dependent on p38 MAP kinase, though direct inhibition of
      cyclooxygenase (COX) activity due to poor inhibitor selectivity may also
      contribute.

PMID- 11520740
TI  - Inflammatory lung injury after bronchial instillation of air pollution particles.
AB  - Epidemiologic investigation has established an association between exposure to
      particulate matter (PM) and human health in the Utah Valley. Reduction of
      particle mass during the temporary closure of a local steel mill was associated
      with diminished morbidity and mortality. We tested the hypothesis that the
      biologic effect of PM would reflect findings of epidemiology with a greater
      injury after exposure to an equal mass of particles from those years in which the
      mill was in operation. Filters containing PM were collected prior to closure of
      the steel mill, during the closure, and after its reopening. Aqueous extracts of
      the filters were prepared. One of three extracts (500 microg) was instilled
      through the bronchoscope into the lungs of nonsmoking volunteers. Twenty-four
      hours later, the same subsegment was lavaged. Exposure to aqueous extracts of PM
      collected before closure and after reopening of the steel mill provoked a greater
      inflammatory response relative to PM extract acquired during the plant shutdown.
      This is the first demonstration that pulmonary effects after experimental
      exposure of humans to PM can correlate with health outcomes observed in
      epidemiologic studies of the same material under normal exposure conditions.
      Findings suggest that mass may not be the most appropriate metric to use in
      assessing health effects after PM exposure but rather specific components must be
      identified and assessed.

PMID- 11520741
TI  - Reduced expression of endothelial nitric oxide synthase in pulmonary arteries of
      smokers.
AB  - Cigarette smoking has been associated with alterations in the structure and
      endothelial function of pulmonary arteries. Nitric oxide (NO) and endothelin-1
      are endothelium-derived mediators with opposite effects on vascular tone and cell
      growth. To investigate whether cigarette smoking could induce changes in the
      synthesis of these mediators in pulmonary arteries, we compared the expression of
      both endothelial NO synthase (eNOS) and endothelin-1 in the lungs of smokers with
      that in nonsmokers. Lung tissue samples of 23 smokers and nine nonsmokers were
      studied. Expression of eNOS and endothelin-1 in pulmonary artery endothelium was
      evaluated by immunohistochemistry. In protein extracts of lung tissue, the
      content of eNOS protein was assessed by Western blot analysis and that of
      endothelin-1 by radioimmunoassay. The immunohistochemical expression of eNOS in
      arterial endothelium and the eNOS protein content in lung tissue were lower in
      the smokers than in the nonsmokers. No differences were shown in cell expression
      and protein content of endothelin-1 between both groups. We conclude that
      cigarette smoking is associated with reduced expression of eNOS in pulmonary
      arteries. The diminished synthesis of nitric oxide may contribute to the
      alterations in the structure and endothelial function of pulmonary vessels in
      cigarette-smoke-induced respiratory disease.

PMID- 11520743
TI  - Retinopathy of prematurity--the "second lull"?

PMID- 11520744
TI  - Who needs an iridotomy?

PMID- 11520745
TI  - Sir Harold Ridley's vision.

PMID- 11520746
TI  - Blindness in children: control priorities and research opportunities.

PMID- 11520747
TI  - A randomised trial of the effect of intraoperative 5-FU on the outcome of
      trabeculectomy in east Africa.
AB  - AIMS: To determine if intraoperative application of 5-fluorouracil (5-FU)
      improves the prognosis for trabeculectomy in east Africa. METHODS: 68 eyes with
      chronic open angle glaucoma were included in a randomised trial of intraoperative
      5-FU versus placebo. Main outcome measures were intraocular pressures at 6 months
      and probability of failure at 2 years. RESULTS: 180 days after surgery the mean
      intraocular pressure (IOP) was 17.4 (SD 6.1) mm Hg in the placebo group and 16.9
      (5.8) mm Hg in the 5-FU group. By 2 years after trabeculectomy, the probability
      of successful IOP control was 70.6% in the placebo group, and 88.8% in the 5-FU
      group. The placebo group was 2.18 times (95% CI 0.67 to 7.15) more likely to
      require additional IOP lowering procedures than the 5-FU group. Among patients
      followed for 2 years, 30% lost 0.3 logMAR units of visual acuity. CONCLUSIONS:
      Trabeculectomy in Africa has an acceptable success rate which may be enhanced by
      the use of intraoperative 5-FU. It is estimated that this would cost
      approximately 1.25 pounds sterling per trabeculectomy failure prevented.

PMID- 11520748
TI  - Ipsilateral limbal translocation for treatment of partial limbal deficiency
      secondary to ocular alkali burn.
AB  - BACKGROUND/AIM: Chemical ocular burn, especially by alkali, may result in damage
      to the limbal stem cells, fundamental in maintaining the integrity of ocular
      surface. Clinically, patients manifest abnormal conjunctival-corneal healing with
      peripheral neovessels, chronic epithelial defect, severe stromal inflammation,
      and conjunctivalisation of the corneal, which is characteristic of limbal
      deficiency. Penetrating keratoplasty has a poor prognosis in these cases.
      Available therapeutic options included limbal autograft and allograft
      transplantation associated or not with human amniotic membrane transplant. The
      authors propose an alternative treatment with ipsilateral autologous limbal
      transplantation, transferring the healthy portion of the limbus from the
      partially burned eye to the deficient area in patients with partial limbal
      deficiency secondary to alkali burn. METHODS: Ipsilateral limbal autografts were
      performed in five patients with partial limbal deficiency secondary to alkali
      burn, transferring the healthy portion of the limbus to the burned area of the
      same eye, without intervening in the contralateral eye. RESULTS: All cases had
      regression of the limbal deficiency with improvement of visual acuity to a
      minimum of 20/60-20/20 (partial), without complications during the follow up
      period (range 7-11 months). CONCLUSION: Ipsilateral autologous limbal autograft
      is a therapeutic option for partial limbal deficient eyes.

PMID- 11520749
TI  - Influence of glistenings on the optical quality of acrylic foldable intraocular
      lens.
AB  - AIMS: To assess the influence of glistenings on the optical quality of acrylic
      foldable intraocular lens. METHODS: Several degrees of glistenings in the optic
      were experimentally created by immersing the lens in water at 37 degrees C for 48
      hours and then at 25 degrees C for 24 hours. Optical bench tests were carried out
      in water including measurements of spectral transmittance with the
      spectrophotometer, intensity of forward scattering using the integrating sphere
      photometer, modulation transfer function, and resolving power at various
      contrasts with and without the veiling glare light source. RESULTS: Glistenings
      of 1+ to 4+ degrees were created, among which the 4+ glistenings seemed to be
      extremely intense and thought to be beyond the range of clinical settings.
      Clinically feasible level of glistenings, up to 3+, did not adversely influence
      spectral transmittance, scattering, modulation transfer function, and resolving
      power at various contrasts. The 4+ glistenings caused mild to moderate
      deteriorations of the optical quality of the lens. CONCLUSION: The optical
      quality of the acrylic foldable intraocular lens is not significantly affected by
      the level of glistenings usually seen in the clinical setting.

PMID- 11520750
TI  - Results of vitrectomy performed at the time of phacoemulsification complicated by
      intravitreal lens fragments.
AB  - AIM: To evaluate outcome of vitrectomy performed at the time of
      phacoemulsification complicated by intravitreal lens material. METHODS: Clinical
      records associated with consecutive 8536 phacoemulsification procedures were
      reviewed retrospectively. RESULTS: 17 (0.20%) eyes had a posterior capsule
      rupture with retained lens material in the vitreous cavity that required
      vitrectomy. Final visual acuity was 0.5 or better in 14 eyes (82%) and 0.4 to 0.1
      in three eyes (18%). Retinal detachment occurred in one eye during vitrectomy and
      two after the surgery. Cystoid macular oedema was observed in two eyes and none
      developed glaucoma. The corneal endothelial cell loss was 5.7% (SD 6.8 %) (n=15)
      at 3-6 months postoperatively. CONCLUSIONS: Combined vitrectomy and intraocular
      lens implantation at the time of phacoemulsification complicated by intravitreal
      lens material is an option to be considered to reduce the risk of postoperative
      complications including secondary glaucoma and corneal endothelial cell damage.

PMID- 11520751
TI  - Surgical removal of subfoveal choroidal neovascularisation in highly myopic
      patients.
AB  - AIM: To analyse the visual results obtained in the treatment of subretinal
      choroidal neovascularisation (CNV) in patients with high myopia by vitrectomy and
      extraction of the neovascular membrane. METHODS: 22 eyes of 22 patients with high
      myopia (>-6 dioptres and/or axial length >26 mm) with subfoveal CNV treated by
      extraction of the CNV were analysed retrospectively. The patients' mean age was
      60.27 (SD 16.41) years (range 32-83 years). The mean follow up was 29.3 (9.9)
      months (range 12-42 months). RESULTS: Best corrected visual acuity (BCVA)
      preoperatively was 0.09 (0.07) (range 0.01-0.3). After treatment BCVA was 0.12
      (0.10) (range 0.01-0.4), a difference without statistical significance (p=0.03,
      Student's t test paired data). In four cases the CNV recurred, in three cases
      cataract developed that required extraction, and in one case retinal detachment
      occurred in the early postoperative period. Topical treatment was necessary in
      two cases to lower the intraocular pressure. CONCLUSIONS: The treatment of
      subfoveal CNV in highly myopic patients by surgical removal by vitrectomy does
      not achieve any significant improvement of the BCVA.

PMID- 11520752
TI  - Is the partial pressure of carbon dioxide in the blood related to the development
      of retinopathy of prematurity?
AB  - AIMS: To determine the role of carbon dioxide in the development of retinopathy
      of prematurity (ROP). METHODS: This was a retrospective cohort study of 25
      consecutive infants admitted to the neonatal unit with continuously recorded
      physiological data. The daily mean and standard deviation (SD) of transcutaneous
      carbon dioxide partial pressure (tcPCO(2)) was compared between infants who had
      stage 1 or 2 ROP and stage 3 ROP. The time spent hypocarbic (<3 kPa) and/or
      hypercarbic (>10 kPa and >12 kPa) was also compared between these groups.
      Intermittent arterial carbon dioxide tension was also measured and compared with
      the simultaneous tcPCO(2) data. RESULTS: There were no significant differences in
      carbon dioxide variability or time spent hypocarbic and/or hypercarbic between
      the ROP groups on any day. 86% of transcutaneous values were within 1.5 kPa of
      the simultaneous arterial value. CONCLUSION: TcPCO(2) measurement can be a very
      useful management technique. However, in this cohort neither variable blood
      carbon dioxide tension nor duration of hypercarbia or hypocarbia in the first 2
      weeks of life was associated with the development or severity of ROP.

PMID- 11520753
TI  - Rhodopsin mutations in Chinese patients with retinitis pigmentosa.
AB  - AIM: To determine the pattern of rhodopsin mutations in Chinese retinitis
      pigmentosa (RP) patients. METHODS: The rhodopsin gene was examined in 101 RP
      patients and 190 controls from Hong Kong. RESULTS: Three coding changes were
      identified: Pro347Leu, Ala299Ser, and 5211delC. Each protein sequence alteration
      was found in one patient. Ala299Ser also existed in two controls. CONCLUSION: The
      C-terminal nonsense mutation may cause mis-sorting of rhodopsin protein. The
      finding of controls with Ala299Ser suggests this is only the third missense
      alteration reported that does not cause RP. The expected frequency of rhodopsin
      mutations in RP is <7% (2/101=2.0%, 95% confidence interval: 0.2%-7.0%).

PMID- 11520754
TI  - Ascertainment of children with congenital cataract through the National
      Congenital Anomaly System in England and Wales.
AB  - BACKGROUND/AIMS: Congenital ocular anomalies contribute significantly to
      childhood visual morbidity, with congenital cataract being a major cause of
      visual impairment throughout the world. As in many other countries, a National
      Congenital Anomaly System (NCAS) exists in England and Wales to monitor the
      frequency of ocular and other anomalies in order to identify new public health
      hazards and inform aetiological research. The aim of this study was to assess
      level of ascertainment by the NCAS of children with congenital cataract. METHODS:
      Using independent ophthalmic and paediatric national active surveillance schemes,
      all infants (< or =1 year) newly diagnosed with congenital and infantile cataract
      in England and Wales in 1 year from September 1995 were identified. These
      notifications were compared with those made independently to the NCAS during the
      same period. The proportion of cases identified by the active surveillance
      schemes and also notified to the NCAS was determined. RESULTS: 10% (15/149) of
      eligible children with newly diagnosed congenital or infantile cataract were
      actually notified to the NCAS. A higher proportion of those diagnosed as neonates
      (16%, 14/85) than in later infancy (2%, 1/64) was ascertained through the NCAS.
      There is a need for better verification of notifications and reported information
      in the NCAS. CONCLUSION: Currently, ascertainment of congenital cataract through
      the NCAS is low and the system is likely to be insensitive to small but important
      changes in risk factors for this disorder. This limits its use for monitoring
      secular and other trends in ocular anomalies. Strategies to improve its future
      use are discussed, including enhancing the awareness and participation of
      ophthalmic professionals involved in managing children with anomalies.

PMID- 11520755
TI  - Comparison between anisometropic and strabismic amblyopia using functional
      magnetic resonance imaging.
AB  - AIMS: To assess calcarine activation with functional magnetic resonance imaging
      (fMRI) in patients with anisometropic and strabismic amblyopia. METHODS: 14
      amblyopes (eight anisometropic and six strabismic) were studied with fMRI using
      stimuli of checkerboards of various checker sizes and temporal frequencies. While
      T2* weighted MRI were obtained every 3 seconds for 6 minutes, patients viewed the
      stimuli monocularly with either the amblyopic or sound eye. RESULTS: Amblyopic
      eyes showed reduced calcarine activation compared with contralateral sound eyes
      in fMRI in all subjects. The calcarine activation from amblyopic eyes in
      anisometropic amblyopes was more suppressed at higher spatial frequencies, while
      that from amblyopic eyes in strabismic amblyopes was more suppressed at lower
      spatial frequencies. CONCLUSION: These results suggest that fMRI is a useful tool
      for the study of amblyopia in humans. The calcarine activation via amblyopic eyes
      because of anisometropia or strabismus has different temporospatial
      characteristics, which suggests differences in the neurophysiological mechanisms
      between two types of amblyopia.

PMID- 11520756
TI  - Anomalies of binocular function in patients with longstanding asymmetric
      keratoconus.
AB  - AIMS: To study binocular function in patients with longstanding asymmetric
      keratoconus. METHODS: In 20 adult patients with longstanding asymmetric
      keratoconus managed with a scleral contact lens a full clinical and orthoptic
      assessment was performed with and without the scleral contact lens in the poorer
      eye. RESULTS: All 20 patients had a corrected acuity of at least 6/9 in their
      better eye. With the scleral lens in situ the acuity of the poorer eye ranged
      from 6/6 to 6/60 and without the lens from 6/18 to hand movements. Patients were
      aged from 18 to 68 years and had worn a scleral contact lens for between 3 and
      106 months. Without the contact lens in their poorer eye all patients had a small
      exotropia and all showed suppression, with the exception of one patient who had a
      right hypertropia with diplopia. With the scleral lens in situ 12 patients had an
      exophoria or esophoria, six a microexotropia, and two a manifest exotropia with
      suppression. CONCLUSIONS: Binocular function breaks down in some adult patients
      with longstanding asymmetric keratoconus. This is probably caused by longstanding
      unilateral visual deprivation. There are similarities to the breakdown of
      binocular function seen in some patients with a longstanding dense unilateral
      adult onset cataract who can develop intractable diplopia following cataract
      surgery.

PMID- 11520757
TI  - Steroid management in giant cell arteritis.
AB  - AIM: Ocular involvement in giant cell arteritis (GCA) is an ophthalmic emergency
      which, if untreated, can progress to permanent blindness. There is little
      evidence in the literature to support current protocols for the acute treatment
      of GCA with steroids. The authors sought to review the effects of intravenous and
      oral steroids in GCA. METHODS: This retrospective study reviewed the records of
      100 consecutive patients with biopsy proved giant cell arteritis. 73 patients
      with visual loss who were treated at the Royal Victorian Eye and Ear Hospital
      (RVEEH) and St Vincent's Hospital were included in the final series. The authors
      studied the management of the patients in the first week after presentation,
      analysing types of treatment, dose, effect on visual acuity, and complications.
      RESULTS: All the patients except one had visual loss due to anterior ischaemic
      optic neuropathy (AION). 17 patients (23%) had bilateral eye involvement. Visual
      acuity improved in 21 of 73 patients (29%) by a mean of two Snellen chart lines
      after commencement of steroids. There was an increased likelihood of improved
      vision in the group who had intravenous steroids (40%) compared with those who
      received oral steroids (13%). In all except four patients (95%) vision remained
      stable at 1 month review. CONCLUSIONS: Prompt treatment of GCA with steroids
      leads to improvement of visual acuity in a significant number of cases.
      Intravenous steroids may offer a greater prospect of improvement compared with
      oral steroids. A prospective trial comparing intravenous with oral steroids is
      needed to validate these findings and would not expose elderly patients to
      unacceptable risks.

PMID- 11520758
TI  - Failure of amniotic membrane transplantation in the treatment of acute ocular
      burns.
AB  - AIM: To report the failure of amniotic membrane transplantation (AMT) for ocular
      surface reconstruction in patients with severe acute chemical and thermal burns.
      METHODS: Four eyes of three patients who suffered severe chemical (n=3) and
      thermal (n=1) burns were studied. The aim of AMT was to prevent symblepharon
      formation, promote conjunctival regeneration, inhibit corneal melting by
      promoting epithelialisation, and to protect the ocular surface while associated
      lid burns were treated. AMT was used to cover the entire ocular surface of all
      the severely burnt and ischaemic eyes, 2-3 weeks after the injury. Where
      indicated, AMT was repeated by itself or in combination with other procedures in
      all patients. RESULTS: Three of the four eyes developed symblepharon and
      progressive corneal melt requiring urgent tectonic keratoplasty. All four eyes
      had persistent epithelial defects. Less than 25% of conjunctival regeneration
      occurred in three eyes. Two eyes autoeviscerated, one patient underwent lid
      sparing exenteration for a painful blind eye and one eye became phthysical.
      CONCLUSIONS: AMT did not help to restore the ocular surface or preserve the
      integrity of the eye in all our patients with severe acute burns, when used by
      itself or in combination with other surgical procedures. This reflects the
      extreme severity of the ocular burns in these patients and, in turn, draws
      attention to the fact that the current classification system does not adequately
      reflect such severity. In the current system such burns would be grouped under
      grade IV injuries to the eye (more than 50% limbal ischaemia). The prognosis of
      patients with 100% limbal ischaemia is much worse than patients with just over
      50% limbal ischaemia. This inadequacy of the classification system probably also
      explains the difference between outcomes of management of grade IV burns (with
      AMT) in this series, compared with others.

PMID- 11520759
TI  - Treatment of fungal keratitis by penetrating keratoplasty.
AB  - AIM: To study the use of penetrating keratoplasty (PKP) for the treatment of
      severe fungal keratitis that could not be cured by antifungal medication.
      METHODS: A retrospective analysis of 108 cases of severe fungal keratitis in
      which PKP was performed served as the basis for this study. Fungal keratitis was
      diagnosed by KOH staining of corneal scrapings or by confocal microscopic imaging
      of the cornea. All patients received a combination of topical and oral antifungal
      medicines without steroids as the first course of therapy. Patients whose corneal
      infection was not cured or in whom the infection progressed during antifungal
      treatment were given a PKP. After surgery, the patients continued to receive
      antifungal therapy with gradual tapering of the dose over a 1-2 month period.
      Cyclosporine was used to prevent graft rejection beginning 2 weeks after PKP.
      Topical steroid only was administered to the patient whose donor graft was over
      8.5 mm and with a heavy iris inflammation 2 weeks after PKP. The surgical
      specimens were used for microbiological evaluation and examined
      histopathologically. The patients were followed for 6-24 months after PKP. Graft
      rejection, clarity of the graft, visual acuity, and surgical complications were
      recorded. RESULTS: Corneal grafts in 86 eyes (79.6%) remained clear during follow
      up. There was no recurrence of fungal infection and the visual acuity ranged from
      40/200 to 20/20. Complications in some patients included recurrent fungal
      infection in eight eyes (7.4%), corneal graft rejection in 32 eyes (29.6%),
      secondary glaucoma in two eyes (1.9%), and five eyes (4.6%) developed cataracts.
      98 of 108 of the recipient corneas had PAS positive fungal hyphae in tissue
      sections; 97 of 108 were culture positive for various fungi, including Fusarium
      (63), Aspergillus (14), Candida (9), Penicillium (4), and seven cases in which
      septate hyphae were seen but identification of the organism was not conclusive.
      CONCLUSIONS: PKP is an effective treatment for fungal keratitis that does not
      respond to antifungal medication. Early surgical intervention before the disease
      becomes advanced is recommended. It is critical that the surgical procedure
      remove the infected tissue in its entirety in order to effect a cure.

PMID- 11520760
TI  - Evaluation of potential organ culture media for eye banking using human donor
      corneas.
AB  - AIM: To evaluate the ability of different commercially available cell culture
      solutions to preserve human donor corneas during 3 weeks of "closed system" organ
      culture at physiological temperature. This screening was performed in an attempt
      to establish a rational basis for the development of a serum-free organ culture
      medium for eye banking. METHODS: 72 normal human donor corneas were organ
      cultured for 21 days at 31 degrees C in eight different test media (nine corneas
      in each group). The basic culture solutions included: minimal essential medium
      (MEM), MEM with stabilised L-glutamine, M199, DIF-1000, SFM, F99, and F99 with
      ascorbic acid, insulin, bFGF, transferrin, selenium, and lipids (termed F99-Sr).
      All media were supplemented with 2% fetal calf serum (FCS), except for MEM, which
      was also studied at 8% FCS. The evaluation parameters included: (1) the
      endothelial cell loss as evaluated using trypan blue staining; (2) the ability of
      keratocytes and endothelial cells to incorporate tritiated uridine into RNA as
      evaluated using autoradiography and digital image analysis; (3) the leakage of
      immunogenic keratan sulphate as assessed using ELISA; and (4) changes in storage
      medium pH, glucose, and lactate content. RESULTS: SFM induced the lowest
      endothelial cell loss of 14% (SD 2%) and the highest RNA synthesis rates of all
      test solutions supplemented with 2% FCS. Corneas stored in SFM also showed the
      least leakage of keratan sulphate and the highest glucose consumption and lactate
      production. In five media (MEM with 2% FCS, MEM with stabilised L-glutamine,
      M199, F99, and F99-Sr), comparable and intermediate potentials for organ culture
      were observed with endothelial cell loss of 16-19%. By contrast, 29% (4%) of the
      endothelium was lost after storage in DIF-1000. Interestingly, the use of 8% FCS
      (in MEM) had a marked protective effect on the endothelium, which showed the
      highest RNA synthetic activity combined with a cell loss of only 11% (4%),
      compared with 19% (6%) at 2% FCS (p<0.05). CONCLUSION: Among the present test
      solutions, SFM appears to be the most prominent candidate for a new corneal organ
      culture medium and should be further tested and possibly refined to effectively
      substitute serum addition.

PMID- 11520761
TI  - Quantification of the ultraviolet radiation (UVR) field in the human eye in vivo
      using novel instrumentation and the potential benefits of UVR blocking hydrogel
      contact lens.
AB  - BACKGROUND/AIMS: Certain degenerative eye conditions occur predominantly nasally,
      at the limbal region, and are associated with solar ultraviolet radiation (UVR)
      induced damage. The relative contribution to the in vivo ocular flux of (a) the
      reflection of UVR incident on the skin of the nose onto the nasal limbus, and (b)
      the focusing of UVR incident on the temporal side of the cornea onto the nasal
      limbus were examined. METHODS: A novel photodiode sensor array was used to
      measure the UVR field across the eye. In addition, a novel spectrometer set-up
      was used to measure the spectrum of radiation refracted across the cornea. The
      efficacy of UVR blocking hydrogel contact lenses in filtering incident UVR was
      assessed in vivo. RESULTS: Qualitative and quantitative data indicated an
      increase nasally of UVR. Photodiode readings showed a net UVR increase from the
      temporal to the nasal side. Transmission curves showed that most UVR incident on
      the limbal region is either absorbed by, or transmitted through, the ocular
      tissues. This radiation is filtered by UVR blocking soft contact lens.
      CONCLUSIONS: An increased UVR flux on the nasal side of the eye, due to
      reflection off the nasal skin, was identified in vivo. Any UVR passing through
      the cornea is either absorbed by the conjunctiva and/or transmitted through it
      onto the sclera where it is absorbed. UVR blocking hydrogel contact lenses can
      eliminate these sources of UVR.

PMID- 11520762
TI  - Histological findings of surgically excised choroidal neovascular membranes after
      photodynamic therapy.
AB  - AIM: To investigate effects of photodynamic therapy (PDT) on human choroidal
      neovascularisation (CNV). METHODS: Two patients with recurrences after PDT with
      verteporfin underwent surgical extraction of the CNV. Immediately after surgical
      excision the subfoveal neovascular membranes were divided for light microscopic
      and for electron microscopic processing. For light microscopy tissues were
      embedded in paraffin. Sections were stained with haematoxylin and eosin, and the
      periodic acid Schiff (PAS) reaction was performed to determine histological
      diagnosis and to ensure tissue quality. For electron microscopy the specimens
      were fixed in glutaraldehyde and embedded in epoxy resin. Semithin sections were
      stained with uranyl acetate and lead citrate and examined with a transmission
      electron microscope. RESULTS: Light microscopy showed thick fibrovascular
      membranes in both cases. On the outer surface remnants of retinal pigment
      epithelial cells resting on thickened inner aspect of Bruch's membrane were
      found. On the retinal side some outer segments were found. The membrane showed
      areas with irregularly shaped vessels. Electron photomicrographs showed occluded
      vessels within the CNV containing thrombotic masses and/or ultrastructural damage
      of the neovascular endothelium. Most of the vessels presented regressive changes
      with vacuolisation and fragmentation of the neovascular endothelium accompanied
      by disintegration of the endothelial cell layer. Extravasation of red blood cells
      was observed. Occasionally, vessels with normal endothelium containing intact red
      blood cells were observed. Some vessels contained immature endothelial cells. At
      some locations the retinal pigment epithelium cells (RPE) were metaplastic
      showing highly vacuolised cytoplasm. CONCLUSIONS: These findings suggest that the
      evidence of fluorescein leakage from the CNV and enlargement of the neovascular
      complex following PDT could be related to new vessel growth and recanalisation of
      occluded vessels. Additionally, RPE disturbances were observed in the specimens.
      This finding may be related to the original pathology or could indicate that PDT
      treatment may result in RPE atrophy.

PMID- 11520763
TI  - Optical coherence tomography of the vitreoretinal interface in macular hole
      formation.
AB  - AIMS: To image the vitreoretinal interface and provide further information on the
      pathogenesis of idiopathic macular hole formation. METHODS: Prospective
      recruitment of 80 eyes of 41 consecutive patients referred with a diagnosis of
      idiopathic full thickness macular hole (FTMH) to a teaching hospital retinal
      clinic. Both eyes of each patient underwent optical coherence tomography (OCT)
      imaging with vertical and horizontal scans centred on the fovea. RESULTS: A total
      of 30 eyes had stage 2 or 3 FTMHs and, of these, 21 had persistent vitreofoveal
      attachment and associated prefoveal opacities. 18 prefoveal opacities were
      identified by Goldmann contact lens examination and confirmed on OCT examination.
      Three prefoveal opacities were identified only on OCT examination. 10 eyes had
      stage 4 FTMHs and four cases were identified in whom the OCT appearance was
      consistent with impending, aborted, or lamellar macular holes. CONCLUSIONS: The
      wide range in OCT appearance of macular holes and associated prefoveal opacities
      suggests that, in at least some cases, a significant amount of retinal tissue is
      torn from the foveal area during macular hole formation. OCT imaging provides
      additional information on macular hole pathogenesis and is valuable in the
      planning of surgical intervention.

PMID- 11520764
TI  - Deletion in the OA1 gene in a family with congenital X linked nystagmus.
AB  - AIMS: To elucidate the molecular genetic defect of X linked congenital nystagmus
      associated with macular hypoplasia in three white males of a three generation
      family with clear features of ocular albinism in only one of them. METHODS: A
      three generation family with congenital nystagmus following X linked inheritance,
      and associated with macular hypoplasia was clinically examined (three males and
      two obligate carriers). Flash VEP was performed to look for albino misrouting.
      DNA samples were subjected to PCR and subsequent analysis using SSCP for all
      exons of the OA1 gene. RT-PCR was performed on a mRNA preparation from a naevus
      from one patient. PCR products presenting divergent banding patterns in SSCP and
      from the RT-PCR were sequenced directly using cycle sequencing with fluorescent
      chain termination nucleotides and electrophoresis in a capillary sequencer.
      RESULTS: The index case (patient 1, IV.1) was diagnosed with X linked OA1 at the
      age of 3 months because of typical clinical features: congenital nystagmus, iris
      translucency, macular hypoplasia, fundus hypopigmentation, normal pigmentation of
      skin and hair, and typical carrier signs of OA1 in his mother and maternal
      grandmother. Pigmentation of the iris and fundus had increased at the last
      examination at age 4 years. Albino misrouting was present at this age. In the
      maternal uncle (III.3, 51 years) who also suffered from congenital nystagmus
      there was clear macular hypoplasia and stromal focal hypopigmentation of the iris
      but no iris translucency or fundus hypopigmentation. Patient 3 (II.3, 79 years,
      maternal uncle of patient III.3) had congenital nystagmus and was highly myopic.
      The fundus appearance was typical for excessive myopia including macular changes.
      The iris did not show any translucency. Molecular genetic analysis revealed a
      novel 14 bp deletion of the OA1 gene at nt816 in exon 6. The mutation abolishes
      four amino acids (Leu 253-Ile-Ile-Cys) and covers the splice site. Nucleotides
      814/815 are used as a new splice donor thus producing a frame shift in codon 252
      and a new stop codon at codon 259. CONCLUSIONS: Macular hypoplasia without
      clinically detectable hypopigmentation as the only sign of X linked OA1 has been
      reported occasionally in African-American, Japanese, and white patients. The
      present family shows absent hypopigmentation in two patients of a white family
      with a deletion in the OA1 gene. We propose a model of OA1 that allows increase
      of pigmentation with age. We hypothesise that macular hypoplasia in all forms of
      albinism depends on the extracellular DOPA level during embryogenesis, and that
      in OA1 postnatal normalisation of the extracellular DOPA level due to delayed
      distribution and membrane budding/fusion of melanosomes in melanocytes results in
      increasing pigmentation.

PMID- 11520765
TI  - Effect of ABO blood group mismatching on corneal epithelial cells: an in vitro
      study.
AB  - AIM: To determine, in vitro, the effects of blood group ABO mismatching on
      corneal epithelial cells. METHODS: Corneal epithelial cell cultures were
      established from 32 human cadaver donor eyes. Epithelial cells (100 microl of 4 x
      10(2) cells per microl) were incubated for 4 hours with antibodies against blood
      group antigens A, B, and AB, with and without complement. Cell lysis was assayed
      by a chemiluminescent assay using Cytolite reagent. Live cells, remaining after
      incubation, were counted in a scintillation counter. The blood group of the
      donors was determined retrospectively, in a blinded manner. RESULTS:
      Retrospective tracing of donor blood groups was possible for 20 donors. In all
      cases the blood group corresponded with that suggested by the cell lysis assay.
      Significant cell lysis was observed when known A group cells were incubated with
      anti-A and anti-AB antibody, B group cells were incubated with anti-B and AB
      antibody, and AB group cells were incubated with anti-AB antibody. Lysis occurred
      only in the presence of complement. No lysis of O group cells was observed with
      any of the antibodies. In all cases, lysis was observed only with neat (serum)
      antibody concentrations. CONCLUSIONS: Blood group ABO mismatching results in
      significant lysis of corneal epithelial cells. The antibody concentration
      required for lysis equals that found in serum. Such levels of antibody are
      unlikely to be achieved in tears and/or aqueous. This may offer an explanation
      for the conflicting reports of the studies on the effect of blood group matching
      on corneal grafts. The variability in the outcome may reflect the levels of
      antibodies gaining access to the corneal cells and not the mismatching alone.

PMID- 11520766
TI  - Pentoxifylline influences the autocrine function of organ cultured donor corneas
      and enhances endothelial cell survival.
AB  - BACKGROUND/AIMS: Scientific interest in pentoxifylline has been reawakened owing
      to the recognised effects of this drug on immune functions, particularly its
      influence on cytokine production. In a previous study, the authors demonstrated
      that spiking of organ culture media with endotoxin elicited a marked enhancement
      in the release of IL-6 and IL-8 from corneal tissue and that these events
      coincided with degenerative changes in endothelial cells and a higher incidence
      of actual loss among this population. Since traces of donor derived endotoxin can
      be detected in up to 50% of corneal organ cultures, this substance may have a
      direct influence on graft viability or trigger inflammatory responses in the
      host. They, therefore, wished to ascertain whether supplementation of media with
      pentoxifylline improved endothelial cell survival in organ cultured donor
      corneas. METHODS: 12 fellow pairs of donor corneas were cultured for 20 days,
      with a change of medium on day 10: One of each pair was incubated in the absence,
      and the other in the presence, of pentoxifylline (25 microg/ml). Samples of
      medium were withdrawn at regular intervals during the course of incubation and
      screened for cytokines IL-6, IL-8, and prostaglandin E2 by ELISA. Endothelial
      cell morphology and numerical density were assessed on days 0, 10 and 20.
      RESULTS: Addition of pentoxifylline to organ culture media led to a significant
      improvement in endothelial cell survival. This drug also elicited a significant
      increase in the level of IL-6 and marginally suppressed that of IL-8 during the
      initial 10 day phase of incubation. During the second 10-20 day phase, the level
      of both IL-6 and IL-8 decreased significantly in the presence of pentoxifylline,
      the relation between these two cytokines being the inverse of that observed in
      the absence of the drug. No significant changes in the level of prostaglandin E2
      were apparent. CONCLUSION: The addition of pentoxifylline to organ culture media
      leads, ultimately, to a suppression of IL-6 and IL-8 secretion by corneal tissue.
      The potentially damaging effects of these cytokines are thereby quelled, as
      evidenced by the improvement in endothelial cell survival.

PMID- 11520767
TI  - Impression cytology following mitomycin C therapy for ocular surface squamous
      neoplasia.
AB  - BACKGROUND/AIMS: Topical mitomycin C (MMC) therapy has been used for treatment of
      ocular surface squamous neoplasia (OSSN) since 1994. Relatively few studies have
      reported the cellular changes in ocular surface following MMC. METHODS:
      Impression cytology was studied in four patients with ocular surface squamous
      neoplasia, either primary or recurrence after previous excisional biopsy. The
      authors studied samples obtained using Millipore filters at intervals between 4
      and 17 weeks after commencement of MMC, and compared them with pretreatment
      cytology. RESULTS: MMC induced changes of cytomegaly, cytoplasmic vacuolation,
      nucleomegaly with nuclear wrinkling, and binucleation or multinucleation were
      seen in some cells in all samples. However, nuclear/cytoplasmic (N/C) ratio in
      these enlarged cells was normal. These changes mimicked those seen following
      radiation therapy in uterine cervix. Changes of increased nuclear and cell size
      with increased N/C ratio were seen in some dysplastic cells. The predominant form
      of cell death was apoptosis with fewer cells showing necrosis. CONCLUSIONS: MMC
      appears to produce cell death in OSSN by apoptosis and necrosis. Cellular changes
      related to MMC mimic those caused by radiation-cytomegaly, nucleomegaly, and
      vacuolation. MMC related changes may persist in ocular surface epithelium for at
      least 8 months following MMC therapy.

PMID- 11520768
TI  - Should we aggressively treat unilateral congenital cataracts?

PMID- 11520769
TI  - Astigmatism and the analysis of its surgical correction.

PMID- 11520772
TI  - Regulated control by granulocyte-macrophage colony-stimulating factor AU-rich
      element during mouse embryogenesis.
AB  - In vitro studies have indicated that the granulocyte-macrophage colony
      stimulating factor (GM-CSF) gene expression is regulated at the
      posttranscriptional level by the AU-rich element (ARE) sequence present in its 3'
      untranslated region (UTR). This study investigated the importance of the ARE in
      the control of GM-CSF gene expression in vivo. For this purpose, transgenic mice
      bearing GM-CSF gene constructs containing or lacking the ARE (GM-CSF AU(+) or GM
      CSF AU(-), respectively) were generated. Both transgenes were under the
      transcriptional control of the immediate early promoter of the cytomegalovirus
      (CMV) to ensure their early, widespread, and constitutive expression. The
      regulation imposed by the ARE was revealed by comparing transgene expression at
      day 14 of embryonic development (E14); only the ARE-deleted but not the ARE
      containing construct was expressed. Although GM-CSF AU(+) embryos were
      phenotypically normal, overexpression of GM-CSF in E14 GM-CSF AU(-) embryos led
      to severe hematopoietic alterations such as abnormal proliferation of
      granulocytes and macrophages accompanied by an increased number of peroxidase
      expressing cells, their putative progenitor cells. These abnormalities compromise
      development because no viable GM-CSF AU(-) transgenic pups could be obtained.
      Surprisingly, by E18, significant accumulation of transgene messenger RNA was
      also observed in GM-CSF AU(+) embryos leading to similar phenotypic
      abnormalities. Altogether, these observations reveal that GM-CSF ARE is a
      developmentally controlled regulatory element and highlight the consequences of
      GM-CSF overexpression on myeloid cell proliferation and differentiation.

PMID- 11520773
TI  - Vascular cell adhesion molecule-1 (CD106) is cleaved by neutrophil proteases in
      the bone marrow following hematopoietic progenitor cell mobilization by
      granulocyte colony-stimulating factor.
AB  - Mobilized progenitor cells currently represent the most commonly used source of
      hematopoietic progenitor cells (HPCs) to effect hematopoietic reconstitution
      following myeloablative chemotherapies. Despite their widespread use, the
      molecular mechanisms responsible for the enforced egress of HPCs from the bone
      marrow (BM) into the circulation in response to mobilizing agents such as
      cytokines remain to be determined. Results of this study indicate that expression
      of vascular cell adhesion molecule-1 (VCAM-1) is strongly reduced in vivo in the
      BM during HPC mobilization by granulocyte colony-stimulating factor (G-CSF) and
      stem cell factor. Two serine proteases, namely, neutrophil elastase and cathepsin
      G, were identified, which cleave VCAM-1 and are released by neutrophils
      accumulating in the BM during the course of immobilization induced by G-CSF. The
      proposal is made that an essential step contributing to the mobilization of HPCs
      is the proteolytic cleavage of VCAM-1 expressed by BM stromal cells, an event
      triggered by the degranulation of neutrophils accumulating in the BM in response
      to the administration of G-CSF.

PMID- 11520774
TI  - Extracorporeal photopheresis in Sezary syndrome: hematologic parameters as
      predictors of response.
AB  - Data were analyzed from 23 patients with Sezary syndrome (defined by
      erythroderma, more than 10% circulating atypical mononuclear cells, and
      peripheral blood T-cell clone) undergoing monthly extracorporeal photopheresis as
      the sole therapy for up to 1 year. The cohort showed a significant reduction of
      skin scores during treatment (P =.001). Thirteen patients (57%) achieved a
      reduction in skin score greater than 25% from baseline at 3, 6, 9, or 12 months
      (responders). Reduction in skin score correlated with reduction in the Sezary
      cell count as a percentage of total white cell count (P =.03). Responders and
      nonresponders were compared. None of the measured parameters was significantly
      different between the 2 groups. It was assessed whether any of the baseline
      parameters predicted outcome. A higher baseline lymphocyte count was
      significantly associated with a decrease in skin score at 6 months (P <.05). A
      higher baseline Sezary cell count as a percentage of total white cell count
      predicted a subject was more likely to be a responder after 6 months of treatment
      (P =.021). No other parameters predicted responder status. These data show that
      the modest falls in CD4, CD8, and Sezary cell counts were seen in all patients
      and might have resulted from lymphocyte apoptosis. This mechanism could explain
      the more favorable response seen in patients with higher percentages of Sezary
      cells in the peripheral blood. Alternatively, minimum tumor burden might be
      required for the induction of a cytotoxic response. Analysis of tumor-specific
      cytotoxic T cells is needed to investigate these possibilities further.

PMID- 11520775
TI  - Attempts to improve treatment outcomes in acute myeloid leukemia (AML) in older
      patients: the results of the United Kingdom Medical Research Council AML11 trial.
AB  - In an attempt to improve induction chemotherapy for older patients with acute
      myeloid leukemia (AML),1314 patients were randomized to 1 of 3 induction
      treatments for 2 courses of DAT (daunorubicin, cytarabine, and thioguanine) 3 +
      10, ADE (daunorubicin, cytarabine, and etoposide) 10 + 3 + 5, or MAC
      (mitoxantrone-cytarabine). The remission rate in the DAT arm was significantly
      better than ADE (62% vs 50%; P =.002) or MAC (62% vs 55%; P =.04). This benefit
      was seen in patients younger and older than 70 years. There were no differences
      between the induction schedules with respect to overall survival at 5 years (12%
      vs 8% vs 10%). A total of 226 patients were randomized to receive granulocyte
      colony-stimulating factor (G-CSF) or placebo as supportive care from day 8 after
      the end of treatment course 1. The remission rate or survival were not improved
      by G-CSF, although the median number of days to recover neutrophils to 1.0 x
      10(9)/L was reduced by 5 days. Patients who entered remission (n = 371) were
      randomized to stop after a third course (DAT 2 + 7) or after 6 courses, ie, a
      subsequent COAP (cyclophosphamide, vincristine, cytarabine, and prednisolone),
      DAT 2 + 5, and COAP. The relapse risk (81% vs 73%), disease-free survival (16% vs
      23%), and overall survival at 5 years (23% vs 22%) did not differ between the 3
      course or 6-course arms. In addition to a treatment duration randomization, 362
      patients were randomized to receive 12-month maintenance treatment with low-dose
      interferon, but no benefit was seen with respect to relapse risk, disease-free
      survival, or overall survival.

PMID- 11520776
TI  - The predictive value of hierarchical cytogenetic classification in older adults
      with acute myeloid leukemia (AML): analysis of 1065 patients entered into the
      United Kingdom Medical Research Council AML11 trial.
AB  - Acute myeloid leukemia (AML) in older adults carries a poor prognosis, and the
      optimum treatment remains to be determined. In younger patients, treatment
      stratification is frequently based upon diagnostic karyotype, which was the most
      important prognostic factor in the UK Medical Research Council (MRC) AML10 trial.
      Considered here is whether karyotype is also predictive in older adults; this is
      done by studying 1065 cases from MRC AML11 (median age, 66 years). Three
      prognostic groups were distinguished on the basis of response to induction
      therapy and overall survival (OS). Those with t(15;17), t(8;21), or inv(16)
      composed the favorable risk group. Overall, these abnormalities predicted a
      superior complete remission (CR) rate (72%), reflecting relatively low levels of
      resistant disease (RD) (8%), and lower relapse risk (RR) (56%) associated with
      superior OS (34% at 5 years). Normal karyotype (CR, 63%; RD, 17%; RR, 78%; OS,
      15%) and other noncomplex abnormalities (CR, 53%; RD, 32%; RR, 85%; OS, 10%)
      composed the intermediate group; while complex karyotype predicted an extremely
      poor prognosis (CR, 26%; RD, 56%; RR, 91%; OS, 2%). Combining MRC AML10 and AML11
      (n = 2677) revealed that the most favorable changes were rarer in older patients
      (younger than 55 years, 24%; 55 years or older, 7%), while complex abnormalities
      were more common (6% vs 13%). This study suggests that hierarchical cytogenetic
      classification identifies biologically distinct subsets of AML that are
      represented in all age groups. Furthermore, it highlights the importance of
      karyotype as a critical independent determinant of outcome in older patients with
      AML, providing a potential framework for stratified treatment approaches.

PMID- 11520777
TI  - Alterations of the X-linked lymphoproliferative disease gene SH2D1A in common
      variable immunodeficiency syndrome.
AB  - X-linked lymphoproliferative (XLP) disease is a primary immunodeficiency caused
      by a defect in the SH2D1A gene. At least 3 major manifestations characterize its
      clinical presentation: fatal infectious mononucleosis (FIM), lymphomas, and
      immunoglobulin deficiencies. Common variable immunodeficiency (CVID) is a
      syndrome characterized by immunoglobulin deficiency leading to susceptibility to
      infection. In some patients with CVID, a defective btk or CD40-L gene has been
      found, but most often there is no clearly identified etiology. Here, 2 unrelated
      families in whom male members were affected by CVID were examined for a defect in
      the XLP gene. In one family previously reported in the literature as having
      progressive immunoglobulin deficiencies, 3 brothers were examined for recurrent
      respiratory infections, whereas female family members showed only elevated serum
      immunoglobulin A levels. A grandson of one of the brothers died of a severe
      Aspergillus infection secondary to progressive immunoglobulin deficiency, FIM,
      aplastic anemia, and B-cell lymphoma. In the second family, 2 brothers had B
      lymphocytopenia and immunoglobulin deficiencies. X-linked agammaglobulinemia
      syndrome was excluded genetically, and they were classified as having CVID. The
      occurrence of FIM in a male cousin of the brothers led to the XLP diagnosis.
      Because the SH2D1A gene was found altered in both families, these findings
      indicate that XLP must be considered when more than one male patient with CVID is
      encountered in the same family, and SH2D1A must be analyzed in all male patients
      with CVID. Moreover, these data link defects in the SH2D1A gene to abnormal B
      lymphocyte development and to dysgammaglobulinemia in female members of families
      with XLP disease.

PMID- 11520778
TI  - Rituximab therapy of patients with B-cell chronic lymphocytic leukemia.
AB  - Rituximab (IDEC-C2B8) is a chimeric antibody that binds to the B-cell surface
      antigen CD20. Rituximab has significant activity in follicular non-Hodgkin
      lymphomas. Much less is known about the effects in chronic lymphocytic leukemia
      (CLL). We have initiated a phase II trial to evaluate the efficacy and safety of
      rituximab in patients with CD20+ pretreated CLL. To avoid the rituximab
      associated toxicity, we restricted the tumor cell load, as measured by the number
      of circulating lymphocytes and the spleen size, in the first 2 cohorts of
      patients included in the study. Patients received 4 intravenous infusions of 375
      mg/m2 once a week over a period of 1 month. Of the 28 patients evaluable for
      response, 7 patients showed a partial remission (National Cancer Institute
      criteria) lasting for a median of 20 weeks, with 1 patient still in remission
      after 71 weeks. Based on lymphocyte counts only, we found at least a 50%
      reduction of lymphocyte counts lasting for at least 4 weeks in 13 (45%) of 29
      patients. Fifteen patients from 3 institutions were monitored for the
      immunophenotype profile of lymphocyte subsets. The number of CD5+CD20+ cells
      decreased significantly and remained low until day 28 after therapy. T-cell
      counts were not affected. With the exception of one rituximab-related death,
      adverse events in the remaining patients were mild. The results suggest that
      rituximab has clinical activity in pretreated patients with B-CLL. Toxicity is
      tolerable. Response duration after withdrawal of rituximab is rather short.
      Therefore, other modes of application and the combination with other agents need
      to be tested.

PMID- 11520779
TI  - Detection of gammopathy by serum protein electrophoresis for predicting and
      managing therapy of lymphoproliferative disorder in 911 recipients of liver
      transplants.
AB  - Monitoring of posttransplantation lymphoproliferative disorder (LPD) is usually
      based on imaging, which lacks sensitivity. A prospective study in 911 consecutive
      recipients of liver transplants was conducted to assess the value of gammopathy
      monitoring by serum protein electrophoresis (SPE) and to compare it with
      conventional follow-up methods. Patients systematically underwent SPE testing
      just before transplantation, at least twice during the first year after
      transplantation, and once a year thereafter. Patients with LPD underwent SPE
      testing every month. Immunofixation was done if abnormalities were detected by
      SPE. Gammopathy was observed in 114 patients, 18 of whom had onset of LPD. In 3
      other patients, LPD developed, but no gammopathy was detected before onset of LPD
      or while LPD was present. Multivariate analyses showed gammopathy (relative risk
      [RR], 65.3), more than one transplantation (RR, 7.5), and viral cirrhosis (RR,
      2.8) to be independent prognostic factors associated with occurrence of LPD. LPD
      was treated by reducing immunosuppression, with or without chemotherapy,
      administration of anti-CD20 monoclonal antibody, or surgery. The mortality rate
      was 24% (5 of 21 patients). Remission, which occurred in 13 patients, was
      associated with disappearance of gammopathy in 10 patients. In 5 patients,
      normalization of SPE results preceded the diagnosis of remission based on
      imaging, by a mean of 4 months. For diagnosis of LPD remission, the positive and
      negative predictive values of disappearance of gammopathy were 91% and 100%,
      respectively; and gammopathy monitoring was more sensitive than imaging (100% and
      38%, respectively). Gammopathy monitoring is an inexpensive, noninvasive,
      sensitive way to detect LPD and assess the efficacy of treatment. It could be
      used routinely in follow-up of recipients of transplants.

PMID- 11520780
TI  - Thrombopoietin therapy increases platelet yields in healthy platelet donors.
AB  - The recombinant thrombopoietins have been shown to be effective stimulators of
      platelet production in cancer patients. It was therefore of interest to determine
      if one of these, pegylated recombinant human megakaryocyte growth and development
      factor (PEG-rHuMGDF), could be used to increase platelet counts and consequently
      platelet yields from apheresis in healthy platelet donors. In a blinded, 2-cycle,
      crossover study, 59 platelet donors were randomized to receive a single
      subcutaneous injection of PEG-rHuMGDF (1 microg/kg or 3 microg/kg) or placebo and
      15 days later undergo platelet apheresis. Donors treated with placebo had a
      median peak platelet count after PEG-rHuMGDF injection of 248 x 10(9)/L compared
      with 366 x 10(9)/L in donors treated with 1 microg/kg PEG-rHuMGDF and 602 x
      10(9)/L in donors treated with 3 microg/kg PEG-rHuMGDF. The median maximum
      percentage that platelet counts increased from baseline was 10% in donors who
      received placebo compared with 70% in donors who received 1 microg/kg and 167% in
      donors who received 3 microg/kg PEG-rHuMGDF. There was a direct relationship
      between the platelet yield and the preapheresis platelet count: Placebo-treated
      donors provided 3.8 x 10(11) (range 1.3 x 10(11)-7.9 x 10(11)) platelets compared
      with 5.6 x 10(11) (range 2.6 x 10(11)-12.5 x 10(11)) or 11.0 x 10(11) (range 7.1
      x 10(11)-18.3 x 10(11)) in donors treated with 1 microg/kg or 3 microg/kg PEG
      rHuMGDF, respectively. Substandard collections (<3 x 10(11) platelets) were
      obtained from 26%, 4%, and 0% of the placebo, 1 microg/kg, and 3 microg/kg
      donors, respectively. No serious adverse events were reported; nor were there
      events that met the criteria for dose-limiting toxicity. Thrombopoietin therapy
      can increase platelet counts in healthy donors to provide a median 3-fold more
      apheresis platelets compared with untreated donors.

PMID- 11520781
TI  - Prophylactic platelet transfusions from healthy apheresis platelet donors
      undergoing treatment with thrombopoietin.
AB  - Many patients receiving dose-intensive chemotherapy acquire thrombocytopenia and
      need platelet transfusions. A study was conducted to determine whether platelets
      harvested from healthy donors treated with thrombopoietin could provide larger
      increases in platelet counts and thereby delay time to next platelet transfusion
      compared to routinely available platelets given to thrombocytopenic patients.
      Community platelet donors received either 1 or 3 microg/kg pegylated recombinant
      human megakaryocyte growth and development factor (PEG-rHuMGDF) or placebo and
      then donated platelets 10 to 15 days later. One hundred sixty-six of these
      platelet concentrates were then transfused to 120 patients with platelets counts
      25 x 10(9)/L or lower. Pretransfusion platelet counts (11 x 10(9)/L) were similar
      for recipients of placebo-derived and PEG-rHuMGDF-derived platelets. Early after
      transfusion, the median platelet count increment was higher in patients receiving
      PEG-rHuMGDF-derived platelets: 19 (range, -12-66) x 10(9)/L, 41 (range, 5-133) x
      10(9)/L, and 82 (range, -4-188) x 10(9)/L for placebo-, 1-microg/kg-, and 3
      micro/kg-derived platelets, respectively. This difference was maintained 18 to 24
      hours after transfusion. Transfusion-free intervals were 1.72, 2.64, and 3.80
      days for the recipients of the placebo-, 1-microg/kg-, and 3-micro/kg-derived
      platelets, respectively. The rate of transfusion-related adverse events was not
      different in recipients of placebo-derived and PEG-rHuMGDF-derived platelets.
      Therefore, when transfused into patients with thrombocytopenia, platelets
      collected from healthy donors undergoing thrombopoietin therapy were safe and
      resulted in significantly greater platelet count increments and longer
      transfusion-free intervals than platelets obtained from donors treated with
      placebo.

PMID- 11520782
TI  - Expression of complement inhibitors CD46, CD55, and CD59 on tumor cells does not
      predict clinical outcome after rituximab treatment in follicular non-Hodgkin
      lymphoma.
AB  - Rituximab is a chimeric monoclonal antibody that targets B-cell-specific antigen
      CD20 and an effective treatment for B-cell non-Hodgkin lymphoma. Although it is
      readily used in clinical practice, the exact mechanism of its antitumor effect is
      unclear. One potential mechanism involves complement-mediated cytotoxicity. It
      has been shown that rituximab induces complement-mediated cytotoxicity in
      follicular lymphoma cells in vitro, and complement inhibitors CD55 and CD59 may
      regulate this process. To determine whether complement inhibitors play a role in
      regulating the antitumor effect of rituximab, the expression of complement
      inhibitors CD46, CD55, and CD59 was analyzed in pretreatment tumor cells from 29
      rituximab-treated follicular lymphoma patients. Among them, 8 patients achieved
      complete responses, 11 patients achieved partial responses, and 10 patients
      showed no or minimal responses to rituximab treatment. Expression of surface
      CD20, CD46, CD55, and CD59 was determined by 2-color flow cytometry. Although the
      CD59 level was slightly lower in the complete response group, there was no
      statistically significant difference in the expression of individual complement
      inhibitor CD46 (mean channel fluorescence [MCF]: NR, 26.4; PR, 21.9; CR, 29.9),
      CD55 (MCF: NR, 16.4; PR, 14.9; CR, 23.2), or CD59 (MCF: NR, 41.6; PR, 40.6; CR,
      30.6), the combination of any 2 inhibitors, or all 3 on tumor cells from 3
      response groups. In addition, there was no difference in the rituximab-induced
      complement-mediated cytotoxicity in an in vitro assay using tumor cells from 3
      response groups. Thus, CD46, CD55, and CD59 expression on pretreatment tumor
      cells, or their susceptibility to in vitro complement-mediated killing, does not
      predict clinical outcome after rituximab treatment.

PMID- 11520783
TI  - Tetramer-based quantification of cytomegalovirus (CMV)-specific CD8+ T
      lymphocytes in T-cell-depleted stem cell grafts and after transplantation may
      identify patients at risk for progressive CMV infection.
AB  - Recovery of cytomegalovirus (CMV)-specific T-cell-mediated immunity after
      allogeneic hematopoietic stem cell transplantation (SCT) is critical for
      protection against CMV disease. The study used fluorochrome-conjugated tetrameric
      complexes of HLA-A2 molecules loaded with the immunodominant NLVPMVATV (NLV)
      peptide derived from the CMV protein pp65 to quantify A2-NLV-specific CD8+ T
      cells in partially T-cell-depleted grafts administered to 27 HLA-A*0201+ patients
      and to monitor recovery of these T cells during the first 12 months after SCT.
      None of the 9 CMV-seronegative patients became infected with CMV, whereas 14 of
      18 CMV-seropositive patients developed CMV antigenemia after SCT. CMV
      seropositive recipients of grafts from CMV-seronegative donors required more
      preemptive treatment with ganciclovir (GCV) than those of grafts from CMV
      seropositive donors (3 [1-6] versus 1 [0-3] courses, respectively; P =.009). The
      number of A2-NLV-specific CD8+ T cells in the grafts correlated inversely with
      the number of preemptive GCV courses administered (r = -0.61; P =.01). None of
      the 9 CMV-seronegative patients mounted a CMV-specific immune response as
      measured by monitoring A2-NLV-specific CD8+ T cells after SCT. Thirteen of 14 CMV
      seropositive patients without CMV disease recovered these T cells. In spite of
      preemptive GCV treatment, CMV disease developed in 4 patients, who all failed to
      recover A2-NLV-specific CD8+ T cells after SCT (P =.002). Thus, enumeration of
      HLA-restricted, CMV-specific CD8+ T cells in the grafts and monitoring of these T
      cells after SCT may constitute a rapid and sensitive tool to identify SCT
      recipients at risk for developing CMV disease.

PMID- 11520784
TI  - Phosphatidylinositol 3 kinase contributes to the transformation of hematopoietic
      cells by the D816V c-Kit mutant.
AB  - Stem cell factor (SCF) binds the receptor tyrosine kinase c-Kit and is critical
      for normal hematopoiesis. Substitution of valine for aspartic acid 816 (D816V)
      constitutively actives human c-Kit, and this mutation is found in patients with
      mastocytosis, leukemia, and germ cell tumors. Immortalized murine progenitor
      cells (MIHCs) transduced with wild-type c-Kit proliferate in response to SCF,
      whereas cells expressing D816V c-Kit (MIHC-D816V) are factor-independent and
      tumorigenic. However, the mechanisms mediating transformation by D816V c-Kit are
      unknown. The objective of this study was to identify signaling components that
      contribute to D816V c-Kit-mediated transformation. SCF stimulates association of
      p85PI3K with phosphorylated tyrosine 721 of wild-type c-Kit. Phosphatidylinositol
      3 kinase (PI3K) subsequently contributes to the activation of Akt and Jnks. In
      contrast, these studies demonstrated that the D816V c-Kit mutant was
      constitutively associated with phosphorylated p85PI3K, and, downstream of PI3K,
      Jnk 1 and Jnk 2 were activated but Akt was not. Interestingly, Erks 1 and 2 were
      not constitutively activated by D816V c-Kit. Thus, D816V c-Kit maintains the
      activity of PI3K but not of all signaling pathways activated by wild-type c-Kit.
      Further, all pathways downstream of PI3K are not constitutively active in MIHC
      D816V cells. Studies with a PI3K inhibitor and D816V/Y721F c-Kit, a mutant
      incapable of recruiting PI3K, indicate that constitutive activation of PI3K
      through direct recruitment by D816V c-Kit plays a role in factor-independent
      growth of MIHC and is critical for tumorigenicity.

PMID- 11520785
TI  - Growth factor withdrawal from primary human erythroid progenitors induces
      apoptosis through a pathway involving glycogen synthase kinase-3 and Bax.
AB  - The prevention of apoptosis is a key function of growth factors in the regulation
      of erythropoiesis. This study examined the role of the constitutively active
      serine/threonine kinase glycogen synthase kinase-3 (GSK3), a target of the
      phosphoinositide-3-kinase (PI3K)/Akt pathway, in the regulation of apoptosis in
      primary human erythroid progenitors. GSK3 phosphorylation at its key regulatory
      residues S21 (alpha isoform) and S9 (beta isoform) was high in steady-state
      culture, disappeared on growth factor withdrawal, and returned in response to
      treatment of cells with either erythropoietin or stem cell factor.
      Phosphorylation correlated with a PI3K-dependent reduction of 25% to 30% in
      measured GSK3 activity. LY294002, a specific inhibitor of PI3K, induced apoptosis
      in growth factor-replete erythroid cells to a degree similar to growth factor
      deprivation, whereas the Mek1 inhibitor U0126 had no effect, implicating PI3K and
      not mitogen-activated protein kinase in survival signaling. Growth factor
      deprived erythroblasts, which undergo apoptosis rapidly, were protected from
      apoptosis by both lithium chloride, a GSK3 selective inhibitor, and inhibition of
      caspase activity. However, the clonogenic potential of single cells, which more
      accurately reflects cell survival, was maintained by lithium chloride, but not by
      caspase inhibition. Furthermore, lithium chloride, but not caspase inhibition,
      prevented the appearance of the conformational form of Bax associated with
      apoptosis induction. In summary, GSK3 activity is suppressed by erythropoietin
      and stem cell factor in human erythroid progenitor cells, and increased GSK3
      activity, brought about by growth factor withdrawal, may regulate commitment to
      cell death through a caspase-independent pathway that results in a conformational
      change in Bax.

PMID- 11520786
TI  - Newly recognized cellular abnormalities in the gray platelet syndrome.
AB  - The gray platelet syndrome (GPS) is a rare congenital bleeding disorder in which
      thrombocytopenia is associated with increased platelet size and decreased alpha
      granule content. This report describes 3 new pediatric cases presenting with the
      classical platelet abnormalities of GPS within one family with normal parents.
      Examination of blood smears of the 3 patients demonstrated not only gray
      platelets, but also gray polymorphonuclear neutrophils (PMNs) with decreased or
      abnormally distributed components of secretory compartments (alkaline
      phosphatase, CD35, CD11b/CD18). Secondary granules were also decreased in number
      as assayed by immunoelectron microscopy. These data confirm that the secretory
      compartments in neutrophils were also deficient in this family. Megakaryocytes
      (MKs) were cultured from the peripheral blood CD34+ cells of the 3 patients for
      14 days, in the presence of thrombopoietin and processed for immunoelectron
      microscopy. Although von Willebrand factor (vWF) was virtually undetectable in
      platelets, vWF immunolabeling was conspicuous in cultured maturing MKs,
      particularly within Golgi saccules, but instead of being packaged in alpha
      granules, it was released into the demarcation membrane system. In contrast, P
      selectin followed a more classical pathway. Double-labeling experiments confirmed
      that vWF was following an intracellular pathway distinct from the one of P
      selectin. In these 3 new cases of GPS, the MKs appeared to abnormally process
      vWF, with secretion into the extracellular space instead of normal alpha-granule
      packaging. Furthermore, the secretory compartment of another blood cell line, the
      neutrophil, was also affected in this family of GPS.

PMID- 11520788
TI  - The Notch ligand, Delta-1, inhibits the differentiation of monocytes into
      macrophages but permits their differentiation into dendritic cells.
AB  - Notch-mediated cellular interactions are known to regulate cell fate decisions in
      various developmental systems. A previous report indicated that monocytes express
      relatively high amounts of Notch-1 and Notch-2 and that the immobilized
      extracellular domain of the Notch ligand, Delta-1 (Delta(ext-myc)), induces
      apoptosis in peripheral blood monocytes cultured with macrophage colony
      stimulating factor (M-CSF), but not granulocyte-macrophage CSF (GM-CSF). The
      present study determined the effect of Notch signaling on monocyte
      differentiation into macrophages and dendritic cells. Results showed that
      immobilized Delta(ext-myc) inhibited differentiation of monocytes into mature
      macrophages (CD1a+/-CD14+/- CD64+) with GM-CSF. However, Delta(ext-myc) permitted
      differentiation into immature dendritic cells (CD1a+CD14-CD64-) with GM-CSF and
      interleukin 4 (IL-4), and further differentiation into mature dendritic cells
      (CD1a+CD83+) with GM-CSF, IL-4, and tumor necrosis factor-alpha (TNF-alpha).
      Notch signaling affected the differentiation of CD1a-CD14+ macrophage/dendritic
      cell precursors derived in vitro from CD34+ cells. With GM-CSF and TNF-alpha,
      exposure to Delta(ext-myc) increased the proportion of precursors that
      differentiated into CD1a+CD14- dendritic cells (51% in the presence of Delta(ext
      myc) versus 10% in control cultures), whereas a decreased proportion
      differentiated into CD1a-CD14+ macrophages (6% versus 65%). These data indicate a
      role for Notch signaling in regulating cell fate decisions by bipotent
      macrophage/dendritic precursors.

PMID- 11520789
TI  - Erythropoietin (Epo) and EpoR expression and 2 waves of erythropoiesis.
AB  - Erythropoiesis occurs in 2 distinct waves during embryogenesis: the primitive
      wave in the extra-embryonic yolk sac (YS) followed by the definitive wave in the
      fetal liver and spleen. Even though progenitors for both cell types are present
      in the YS blood islands, only primitive cells are formed in the YS during early
      embryogenesis. In this study, it is proposed that erythropoietin (Epo) expression
      and the resultant EpoR activation regulate the timing of the definitive wave.
      First, it was demonstrated that Epo and EpoR gene expressions are temporally and
      spatially segregated: though EpoR is expressed early (embryonic days 8.0-9.5) in
      the yolk sac blood islands, no Epo expression can be detected in this extra
      embryonic tissue. Only at a later stage can Epo expression be detected intra
      embryonically, and the onset of Epo expression correlates with the initiation of
      definitive erythropoiesis. It was further demonstrated that the activation of the
      EpoR signaling pathway by knocking-in a constitutively active form of EpoR (R129C
      EpoR) can lead to earlier onset of definitive erythropoiesis in the YS. Thus,
      these results provide the first in vivo mechanism as to how 2 erythroid
      progenitor populations can coexist concurrently in the YS yet always
      differentiate successively during embryogenesis.

PMID- 11520787
TI  - The Fanconi anemia complementation group C gene product: structural evidence of
      multifunctionality.
AB  - The Fanconi anemia (FA) group C gene product (FANCC) functions to protect cells
      from cytotoxic and genotoxic effects of cross-linking agents. FANCC is also
      required for optimal activation of STAT1 in response to cytokine and growth
      factors and for suppressing cytokine-induced apoptosis by modulating the activity
      of double-stranded RNA-dependent protein kinase. Because not all FANCC mutations
      affect STAT1 activation, the hypothesis was considered that cross-linker
      resistance function of FANCC depends on structural elements that differ from
      those required for the cytokine signaling functions of FANCC. Structure-function
      studies were designed to test this notion. Six separate alanine-substituted
      mutations were generated in 3 highly conserved motifs of FANCC. All mutants
      complemented mitomycin C (MMC) hypersensitive phenotype of FA-C cells and
      corrected aberrant posttranslational activation of FANCD2 in FA-C mutant cells.
      However, 2 of the mutants, S249A and E251A, failed to correct defective STAT1
      activation. FA-C lymphoblasts carrying these 2 mutants demonstrated a defect in
      recruitment of STAT1 to the interferon gamma (IFN-gamma) receptor and GST-fusion
      proteins bearing S249A and E251A mutations were less efficient binding partners
      for STAT1 in stimulated lymphoblasts. These same mutations failed to complement
      the characteristic hypersensitive apoptotic responses of FA-C cells to tumor
      necrosis factor-alpha (TNF-alpha) and IFN-gamma. Cells bearing a naturally
      occurring FANCC mutation (322delG) that preserves this conserved region showed
      normal STAT1 activation but remained hypersensitive to MMC. The conclusion is
      that a central highly conserved domain of FANCC is required for functional
      interaction with STAT1 and that structural elements required for STAT1-related
      functions differ from those required for genotoxic responses to cross-linking
      agents. Preservation of signaling capacity of cells bearing the del322G mutation
      may account for the reduced severity and later onset of bone marrow failure
      associated with this mutation.

PMID- 11520790
TI  - Functional mapping of anti-factor IX inhibitors developed in patients with severe
      hemophilia B.
AB  - Development of inhibitory antibodies is a serious complication of treatment with
      repeated factor IX infusions in a minority of patients with hemophilia B. Such
      antibodies detected in 8 patients have been characterized. Typing studies
      revealed that patients' immune response toward factor IX is highly heterogeneous
      and involves immunoglobulin G (IgG) antibodies, preferentially IgG1 and IgG4. The
      preservation of the sequence and the 3-dimensional orientation of the amino acids
      constituting one epitope are highly important for the assembly of an antibody
      antigen complex. To localize the epitopes on the factor IX molecule, an original
      approach was designed using a set of factor X chimeras carrying regions of factor
      IX. Results showed that some patients' antibodies were directed against both the
      domain containing the gamma-carboxy glutamic acid residues (Gla domain) and the
      protease domain of factor IX. In contrast, no binding was observed to the
      epidermal growth factor-like domains or to the activation peptide. Functional
      characterization showed that the purified IgG from patients' serum inhibited the
      factor VIIIa-dependent activation of factor X. Moreover, patients' IgG directed
      against the Gla domain inhibited the binding of factor IX to phospholipids as
      well as the binding of factor VIII light chain to factor IXa. These data
      demonstrate that inhibitors appearing in patients with severe hemophilia B
      display specificity against restricted functional domains of factor IX.

PMID- 11520791
TI  - Localized reduction of atherosclerosis in von Willebrand factor-deficient mice.
AB  - To examine the role of the platelet adhesion molecule von Willebrand factor (vWf)
      in atherogenesis, vWf-deficient mice (vWf-/-) were bred with mice lacking the low
      density lipoprotein receptor (LDLR-/-) on a C57BL/6J background. LDLR-/-vWf+/+
      and LDLR-/-vWf-/- mice were placed on a diet rich in saturated fat and
      cholesterol for different lengths of time. The atherogenic diet stimulated
      leukocyte rolling in the mesenteric venules in both genotypes, indicating an
      increase in P-selectin-mediated adhesion to the endothelium. After 8 weeks on the
      atherogenic diet, the fatty streaks formed in the aortic sinus of LDLR-/-vWf-/-
      mice of either sex were 40% smaller and contained fewer monocytes than those in
      LDLR-/-vWf+/+ mice. After 22 weeks on the atherogenic diet (early fibrous plaque
      stage), the difference in lesion size in the aortic sinus persisted.
      Interestingly, the lesion distribution in the aortas of LDLR-/-vWf-/- animals was
      different from that of LDLR-/- vWf+/+ animals. In vWf-positive mice, half of all
      lesions were located at the branch points of the renal and mesenteric arteries,
      whereas lesions in this area were not as prominent in the vWf-negative mice.
      These results indicate that the absence of vWf primarily affects the regions of
      the aorta with disturbed flow that are prone to atherosclerosis. Thus, vWf may
      recruit platelets/leukocytes to the lesion in a flow-dependent manner or may be
      part of the mechano-transduction pathway regulating endothelial response to shear
      stress.

PMID- 11520792
TI  - Lipopolysaccharide activation of the MEK-ERK1/2 pathway in human monocytic cells
      mediates tissue factor and tumor necrosis factor alpha expression by inducing Elk
      1 phosphorylation and Egr-1 expression.
AB  - Lipopolysaccharide (LPS) induces human monocytes to express many proinflammatory
      mediators, including the procoagulant molecule tissue factor (TF) and the
      cytokine tumor necrosis factor alpha (TNF-alpha). The TF and TNF-alpha genes are
      regulated by various transcription factors, including nuclear factor (NF)
      kappaB/Rel proteins and Egr-1. In this study, the role of the MEK-ERK1/2 mitogen
      activated protein kinase (MAPK) pathway in LPS induction of TF and TNF-alpha gene
      expression in human monocytic cells was investigated. The MAPK kinase (MEK)1
      inhibitor PD98059 reduced LPS induction of TF and TNF-alpha expression in a dose
      dependent manner. PD98059 did not affect LPS-induced nuclear translocation of NF
      kappaB/Rel proteins and minimally affected LPS induction of kappaB-dependent
      transcription. In contrast, PD98059 and dominant-negative mutants of the Ras-Raf1
      MEK-ERK (extacellular signal-regulated kinase) pathway strongly inhibited LPS
      induction of Egr-1 expression. In kinetic experiments LPS induction of Egr-1
      expression preceded induction of TF expression. In addition, mutation of the Egr
      1 sites in the TF and TNF-alpha promoters reduced expression of these
      proinflammatory genes. It was demonstrated that LPS induction of the Egr-1
      promoter was mediated by 3 SRE sites, which bound an LPS-inducible complex
      containing serum response factor and Elk-1. LPS stimulation transiently induced
      phosphorylation of Elk-1 and increased the functional activity of a GAL4-Elk-1TA
      chimeric protein via the MEK-ERK1/2 pathway. The data indicate that LPS induction
      of Egr-1 gene expression is required for maximal induction of the TNF-alpha and
      TF genes in human monocytic cells.

PMID- 11520793
TI  - Regulation of P-selectin binding to the neutrophil P-selectin counter-receptor P
      selectin glycoprotein ligand-1 by neutrophil elastase and cathepsin G.
AB  - In the inflammatory response, leukocyte rolling before adhesion and
      transmigration through the blood vessel wall is mediated by specific cell surface
      adhesion receptors. Neutrophil rolling involves the interaction of P-selectin
      expressed on activated endothelium and its counter-receptor on neutrophils, P
      selectin glycoprotein ligand-1 (PSGL-1). Here, it is reported that P-selectin
      binding to neutrophils is lost under conditions that cause the release of
      proteinases from neutrophil primary granules. Treatment of neutrophils with the
      purified neutrophil granule proteinases, cathepsin G and elastase, rapidly
      abolished their capacity to bind P-selectin. This inactivation corresponded to
      loss of the N-terminal domain of PSGL-1, as assessed by Western blot analysis. A
      loss of intact PSGL-1 protein from the surfaces of neutrophils after the
      induction of degranulation was also detected by Western blot analysis. Cathepsin
      G initially cleaved near the PSGL-1 N-terminus, whereas neutrophil elastase
      predominantly cleaved at a more C-terminal site within the protein mucin core.
      Consistent with this, cathepsin G cleaved a synthetic peptide based on the PSGL-1
      N-terminus between Tyr-7/Leu-8. Under conditions producing neutrophil
      degranulation in incubations containing mixtures of platelets and neutrophils,
      the loss of PSGL-1, but not P-selectin, from platelet-neutrophil lysates was
      detected. Cathepsin G- or neutrophil elastase-mediated PSGL-1 proteolysis may
      constitute a potential autocrine mechanism for down-regulation of neutrophil
      adhesion to P-selectin.

PMID- 11520795
TI  - Platelet endothelial cell adhesion molecule-1 is a negative regulator of platelet
      collagen interactions.
AB  - The functional importance of platelet endothelial cell adhesion molecule-1 (PECAM
      1/CD31) in platelets is unclear. Because PECAM-1 represents a newly assigned
      immunoglobulin-ITIM superfamily member expressed on the surface of platelets, it
      was hypothesized that it may play an important regulatory role in modulating ITAM
      bearing receptors such as collagen (GP)VI receptor and FcgammaRIIA. To examine
      the functional role of PECAM-1 in regulating platelet-collagen interactions, 2
      different approaches were applied using recombinant human PECAM-1-immunoglobulin
      chimeras and platelets derived from PECAM-1-deficient mice. Stimulation of
      platelets by collagen-, (GP)VI-selective agonist, collagen-related peptide (CRP)
      , and PECAM-1-immunoglobulin chimera induced tyrosine phosphorylation of PECAM-1
      in a time- and dose-dependent manner. Activation of PECAM-1 directly through the
      addition of soluble wild-type PECAM-1-immunoglobulin chimera, but not mutant K89A
      PECAM-1-immunoglobulin chimera that prevents homophilic binding, was found to
      inhibit collagen- and CRP-induced platelet aggregation. PECAM-1-deficient
      platelets displayed enhanced platelet aggregation and secretion responses on
      stimulation with collagen and CRP, though the response to thrombin was
      unaffected. Under conditions of flow, human platelet thrombus formation on a
      collagen matrix was reduced in a dose-dependent manner by human PECAM-1
      immunoglobulin chimera. Platelets derived from PECAM-1-deficient mice form larger
      thrombi when perfused over a collagen matrix under flow at a shear rate of 1800
      seconds(-1) compared to wild-type mice. Collectively, these results indicate that
      PECAM-1 serves as a physiological negative regulator of platelet-collagen
      interactions that may function to negatively limit growth of platelet thrombi on
      collagen surfaces.

PMID- 11520794
TI  - Antineutrophil cytoplasm autoantibodies from patients with systemic vasculitis
      activate neutrophils through distinct signaling cascades: comparison with
      conventional Fcgamma receptor ligation.
AB  - In systemic vasculitis, interactions between antineutrophil cytoplasm
      autoantibodies (ANCAs) and neutrophils initiate endothelial and vascular injury.
      ANCAs directed against either myeloperoxidase (MPO) or proteinase 3 (PR3) can
      activate cytokine-primed neutrophils by binding cell surface-expressed MPO or
      PR3, with the concurrent engagement of Fcgamma receptors (FcgammaR). Because
      roles for phospholipase D (PLD) and phosphatidylinositol 3 kinase (PI3K) have
      been demonstrated in FcgammaR activation of neutrophils, this study investigated
      the hypothesis that ANCA stimulation of neutrophils involved a similar engagement
      of FcgammaR and activation of PLD and PI3K. Pretreatment of tumor necrosis factor
      (TNF) alpha-primed neutrophils with antibodies against FcgammaRII and FcgammaRIII
      inhibited MPO-ANCA and PR3-ANCA induced superoxide generation, confirming that
      FcgammaR ligation is involved in ANCA-mediated neutrophil activation. However,
      although stimulation of TNF-alpha-primed neutrophils by conventional FcgammaR
      ligation, either using antibody-mediated cross-linking of FcgammaR or aggregated
      IgG, induced PLD activation, ANCA stimulation did not. Moreover, although ANCA
      induced neutrophil activation results in significant PI3K activation-as assessed
      by phosphatidylinositol 3,4,5-triphosphate generation-conventional FcgammaR
      ligation, but not ANCA, activates the p85/p110 PI3K subtype. Inhibition of ANCA
      induced superoxide generation with pertussis toxin suggests that ANCAs activate
      the p101/p110gamma PI3K isoform. In addition, the kinetics of activation of
      protein kinase B differs between conventional FcgammaR ligation and ANCA
      stimulation of neutrophils. These results demonstrate that though ligation of
      FcgammaRIIa and FcgammaRIIIb may be necessary, it is likely that ANCAs require
      other membrane cofactors for neutrophil activation.

PMID- 11520796
TI  - Identification of anti-herpes simplex virus antibody-producing B cells in a
      patient with an atypical RAG1 immunodeficiency.
AB  - Mutations of the RAG1 or RAG2 protein that eliminate their recombination activity
      result in T-B-severe combined immunodeficiency (SCID), whereas mutations
      retaining partial recombination activity lead to Omenn syndrome, a peculiar SCID
      characterized by increased host T cells and absence of circulating B cells. The
      prognosis of this disease is fatal, unless hematopoietic stem cell
      transplantation is performed. This study reports a case of atypical SCID,
      carrying RAG1 mutations. The patient survived for 6 years without hematopoietic
      stem cell transplantation. The missense mutation, tested by in vivo recombination
      assay, revealed residual recombination activity. By the age of 5 years, the
      patient developed host B cells, but not T cells, possibly due to engrafted
      maternal T cells. In addition, the host B cells were able to produce antibodies,
      including anti-herpes simplex virus-antibodies. The fact that host B cells could
      produce antibodies in this patient could explain not only the mild phenotype
      observed but also, at least in part, how patients with Omenn syndrome produce
      immunoglobulin E and sometimes immunoglobulin M, as the same missense mutation of
      RAG1 gene has been reported in a patient with Omenn syndrome.

PMID- 11520797
TI  - Homophilic adhesion of human CEACAM1 involves N-terminal domain interactions:
      structural analysis of the binding site.
AB  - CEACAM1 on leukocytic, endothelial, and epithelial cells functions in homophilic
      adhesion, tumor suppression, regulating cell adhesion and proliferation, and in
      heterophilic adhesion as a receptor for E-selectin and Neisseria meningiditis,
      Neisseria gonorrhoeae, Haemophilus influenzae, and murine coronaviruses. The 8
      transmembrane isoforms of human CEACAM1 possess an extracellular N-terminal IgV
      domain, followed by variable numbers of IgC2 domains. To establish which key
      amino acids contribute specifically to CEACAM1 homophilic adhesion, exposed amino
      acids in the N-terminal domain of a soluble form of CEACAM1 were subjected to
      mutagenesis. Analyses of mutant proteins with conformationally dependent
      antibodies indicated that most mutations did not substantially affect the
      structural integrity of CEACAM1. Nevertheless, decreased adhesion was observed
      for the single mutants V39A or D40A (single-letter amino acid codes) in the CC'
      loop and for the triple mutants located in the GFCC'C" face of the N-terminal
      domain. Interestingly, whereas single mutations in R64 or D82 that are predicted
      to form a salt bridge between the base of the D and F beta strands close to the
      critical V39 and D40 residues also abolish adhesion, an amino acid swap (R64D and
      D82R), which maintains the salt bridge was without significant effect. These
      studies indicate that the CC' loop plays a crucial role in the homophilic
      adhesion of CEACAM1. They further predict that specific hydrophobic amino acid
      residues on the nonglycosylated GFCC'C" face of CEACAM1 N-terminal domain are not
      only involved in heterophilic interactions with Opa proteins and H influenzae,
      but are also critical for protein-protein interactions between 2 CEACAM1
      molecules on opposing cells.

PMID- 11520798
TI  - Regulation of interferon-gamma gene expression by nuclear factor of activated T
      cells.
AB  - Transcription factors of the nuclear factor of activated T cells (NFAT) family
      are thought to regulate the expression of a variety of inducible genes such as
      interleukin-2 (IL-2), IL-4, and tumor necrosis factor-alpha. However, it remains
      unresolved whether NFAT proteins play a role in regulating transcription of the
      interferon- gamma (IFN-gamma) gene. Here it is shown that the transcription
      factor NFAT1 (NFATc2) is a major regulator of IFN-gamma production in vivo.
      Compared with T cells expressing NFAT1, T cells lacking NFAT1 display a
      substantial IL-4-independent defect in expression of IFN-gamma mRNA and protein.
      Reduced IFN-gamma production by NFAT1(-/-)x IL-4(-/-) T cells is observed after
      primary in vitro stimulation of naive CD4+ T cells, is conserved through at least
      2 rounds of T-helper cell differentiation, and occurs by a cell-intrinsic
      mechanism that does not depend on overexpression of the Th2-specific factors GATA
      3 and c-Maf. Concomitantly, NFAT1(-/-)x IL-4(-/-) mice show increased
      susceptibility to infection with the intracellular parasite Leishmania major.
      Moreover, IFN-gamma production in a murine T-cell clone is sensitive to the
      selective peptide inhibitor of NFAT, VIVIT. These results suggest that IFN-gamma
      production by T cells is regulated by NFAT1, most likely at the level of gene
      transcription.

PMID- 11520799
TI  - Role for lipid rafts in regulating interleukin-2 receptor signaling.
AB  - Lipid rafts are plasma membrane microdomains characterized by a unique lipid
      environment enriched in gangliosides and cholesterol, leading to their
      insolubility in nonionic detergents. Many receptors are constitutively or
      inducibly localized in lipid rafts, which have been shown to function as
      platforms coordinating the induction of signaling pathways. In this report, the
      first evidence is provided for a role of these lipid microdomains in regulating
      interleukin-2 receptor (IL-2R) signaling. It is demonstrated that antibody- or
      ligand-mediated immobilization of components of lipid rafts, glycosyl
      phosphatidyl-inositol-anchored proteins, and the GM1 ganglioside, respectively,
      inhibit IL-2-induced proliferation in T cells. IL-2Ralpha is shown to be
      constitutively enriched in rafts and further enriched in the presence of
      immobilized anti-Thy-1. In contrast, IL-2Rbeta and IL-2Rgamma, as well as JAK1
      and JAK3, are found in soluble membrane fractions, and their localization is not
      altered by anti-Thy-1. IL-2-mediated heterotrimerization of IL-2R chains is shown
      to occur within soluble membrane fractions, exclusively, as is the activation of
      JAK1 and JAK3. As predicted by these results, the disruption of lipid raft
      integrity did not impair IL-2-induced signaling. Thus, the sequestration of IL
      2Ralpha within lipid microdomains restricts its intermolecular interactions and
      regulates IL-2R signaling through impeding its association with IL-2Rbeta and IL
      2Rgamma.

PMID- 11520800
TI  - HLA class II-restricted antigen presentation of endogenous bcr-abl fusion protein
      by chronic myelogenous leukemia-derived dendritic cells to CD4(+) T lymphocytes.
AB  - Bcr-abl fusion peptide-specific CD4+ T-lymphocyte clones have recently been shown
      to augment colony formation by chronic myelogenous leukemia (CML) cells in a bcr
      abl type-specific and HLA class II-restricted manner without addition of
      exogenous antigen. These findings suggest that CML cells can naturally process
      and present endogenous bcr-abl fusion protein to CD4+ T lymphocytes in the
      context of HLA class II molecules. To verify this possibility, the ability of CML
      derived dendritic cells (DCs) to present endogenous bcr-abl fusion protein to bcr
      abl fusion peptide-specific CD4+ T-lymphocyte clones was investigated. The bcr
      abl b3a2 peptide-specific and HLA-DRB1*0901-restricted CD4+ T-lymphocyte clones
      produced interferon-gamma in response to stimulation with monocyte-derived DCs
      from HLA-DRB1*0901+ patients with b3a2 type CML. In contrast, DCs from patients
      with HLA-DRB1*0901- or b2a2 type CML and those from healthy individuals did not
      exert stimulatory activity on bcr-abl-specific CD4+ T-lymphocyte clones. The
      response of CD4+ T-lymphocyte clones to CML-derived mature DCs was higher than
      that to immature DCs and was inhibited by anti-HLA-DR monoclonal antibody. These
      data suggest that CML-derived DCs can process and present endogenous bcr-abl
      fusion protein to CD4+ T lymphocytes.

PMID- 11520801
TI  - In vitro spontaneous lymphoproliferation in patients with human T-cell
      lymphotropic virus type I-associated neurologic disease: predominant expansion of
      CD8+ T cells.
AB  - Peripheral blood mononuclear cells (PBMCs) from patients with human T-cell
      lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic
      paraparesis (HAM/TSP) proliferate spontaneously in vitro. This spontaneous
      lymphoproliferation (SP) is one of the immunologic hallmarks of HAM/TSP and is
      considered to be an important factor related to the pathogenesis of HAM/TSP.
      However, the cell populations involved in this phenomenon have not yet been
      definitively identified. To address this issue, the study directly evaluated
      proliferating cell subsets in SP with a flow cytometric method using
      bromodeoxyuridine and Ki-67. Although both CD4+ and CD8+ T cells proliferated
      spontaneously, the percentage of proliferating CD8+ T cells was 2 to 5 times
      higher than that of CD4+ T cells. In addition, more than 40% of HTLV-I Tax11-19
      specific CD8+ T cells as detected by an HLA-A*0201/Tax11-19 tetramer proliferated
      in culture. In spite of this expansion of HTLV-I-specific CD8+ T cells, HTLV-I
      proviral load did not decrease. This finding will help elucidate the dynamics of
      in vivo virus-host immunologic interactions that permit the coexistence of high
      HTLV-I-specific CD8+ cytotoxic T-lymphocyte responses and high HTLV-I proviral
      load in HAM/TSP.

PMID- 11520802
TI  - Cytokine production by mouse myeloid dendritic cells in relation to
      differentiation and terminal maturation induced by lipopolysaccharide or CD40
      ligation.
AB  - Although it is known that dendritic cells (DCs) produce cytokines, there is
      little information about how cytokine synthesis is regulated during DC
      development. A range of cytokine mRNA/proteins was analyzed in immature (CD86-)
      or mature (CD86+) murine bone marrow (BM)- derived DCs. Highly purified, flow
      sorted, immature DCs exhibited higher amounts of interleukin-1alpha (IL-1alpha),
      IL-1beta, tumor necrosis factor-alpha (TNF-alpha), transforming growth factor
      beta1 (TGF-beta1), and macrophage migration inhibitory factor (MIF) mRNA/protein
      than mature DCs. After differentiation, DC up-regulated the levels of IL-6 and IL
      15 mRNA/protein and synthesized de novo mRNA/protein for IL-12p35, IL-12p40, and
      IL-18. Although immature BM-derived DCs did not stimulate naive allogeneic T
      cells, mature DCs elicited a mixed population of T helper (Th) 1 (mainly) and Th2
      cells in 3d-mixed leukocyte reactions. CD86+ BM DCs switched to different
      cytokine patterns according to whether they were terminally differentiated by
      lipopolysaccharide (LPS) or CD40 ligation. Although both stimuli increased IL-6,
      IL-12p40, IL-15, and TNF-alpha mRNA/protein levels, only LPS up-regulated
      transcription of IL-1alpha, IL-1beta, IL-12p35, and MIF genes. Although LPS and
      CD40 cross-linking increased the T-cell allostimulatory function of BM DCs, only
      LPS stimulation shifted the balance of naive Th differentiation to Th1 cells, a
      mechanism dependent on the up-regulation of IL-12p35 and not of IL-23. These
      results demonstrate that, depending on the stimuli used to terminally mature BM
      DCs, DCs synthesize a different pattern of cytokines and exhibit distinct Th cell
      driving potential.

PMID- 11520803
TI  - Interleukin-7 promotes survival and cell cycle progression of T-cell acute
      lymphoblastic leukemia cells by down-regulating the cyclin-dependent kinase
      inhibitor p27(kip1).
AB  - In normal T-cell development interleukin-7 (IL-7) functions as an antiapoptotic
      factor by regulating bcl-2 expression in immature thymocytes and mature T cells.
      Similar to what occurs in normal immature thymocytes, prevention of spontaneous
      apoptosis by IL-7 in precursor T-cell acute lymphoblastic leukemia (T-ALL) cells
      correlates with up-regulation of bcl-2. IL-7 is also implicated in leukemogenesis
      because IL-7 transgenic mice develop lymphoid malignancies, suggesting that IL-7
      may regulate the generation and expansion of malignant cells. This study shows
      that in the presence of IL-7, T-ALL cells not only up-regulated bcl-2 expression
      and escaped apoptosis but also progressed in the cell cycle, resulting in
      sequential induction of cyclin D2 and cyclin A. Down-regulation of p27kip1 was
      mandatory for IL-7-mediated cell cycle progression and temporally coincided with
      activation of cyclin-dependent kinase (cdk)4 and cdk2 and hyperphosphorylation of
      Rb. Strikingly, forced expression of p27kip1 in T-ALL cells not only prevented
      cell cycle progression but also reversed IL-7-mediated up-regulation of bcl-2 and
      promotion of viability. These results show for the first time that a causative
      link between IL-7-mediated proliferation and p27kip1 down-regulation exists in
      malignant T cells. Moreover, these results suggest that p27kip1 may function as a
      tumor suppressor gene not only because it is a negative regulator of cell cycle
      progression but also because it is associated with induction of apoptosis of
      primary malignant cells.

PMID- 11520804
TI  - Adhesion to fibronectin selectively protects Bcr-Abl+ cells from DNA damage
      induced apoptosis.
AB  - The phenotype of Bcr-Abl-transformed cells is characterized by a growth factor
      independent survival and a reduced susceptibility to apoptosis. Furthermore, Bcr
      Abl kinase alters adhesion features by phosphorylating cytoskeletal and/or
      signaling proteins important for integrin function. Integrin-mediated adhesion to
      extracellular matrix molecules is critical for the regulation of growth and
      apoptosis. However, effects of integrin signaling on regulation of apoptosis in
      cells expressing Bcr-Abl are largely unknown. The influence of adhesion on
      survival and apoptosis in Bcr-Abl+ and Bcr-Abl- BaF3 cells was investigated.
      p185bcr-abl-transfected BaF3 cells preadhered to immobilized fibronectin had a
      significant survival advantage and reduced susceptibility to apoptosis following
      gamma-irradiation when compared with the same cells grown on laminin, on
      polylysin, or in suspension. Both inhibition of Bcr-Abl kinase by STI571 and
      inhibition of specific adhesion reversed the fibronectin-mediated antiapoptotic
      effect in BaF3p185. The DNA damage response of Bcr-Abl- BaF3 cells was not
      affected by adhesion to fibronectin. In contrast to parental BaF3 cells, BaF3p185
      adherent to fibronectin did not release cytochrome c to the cytosol following
      irradiation. The fibronectin-mediated antiapoptotic mechanism in Bcr-Abl-active
      cells was not mediated by overexpression of Bcl-XL or Bcl-2 but required an
      active phosphatidylinositol 3-kinase (PI-3K). Kinase-active Bcr-Abl in
      combination with fibronectin-induced integrin signaling led to a
      hyperphosphorylation of AKT. Thus, cooperative activation of PI-3K/AKT by Bcr-Abl
      and integrins causes synergistic protection of Bcr-Abl+ cells from DNA damage
      induced apoptosis.

PMID- 11520805
TI  - Rapid extracellular release of cytochrome c is specific for apoptosis and marks
      cell death in vivo.
AB  - Diverse death stimuli including anticancer drugs trigger apoptosis by inducing
      the translocation of cytochrome c from the outer mitochondrial compartment into
      the cytosol. Once released, cytochrome c cooperates with apoptotic protease
      activating factor-1 and deoxyadenosine triphosphate in caspase-9 activation and
      initiation of the apoptotic protease cascade. The results of this study show that
      on death induction by chemotherapeutic drugs, staurosporine and triggering of the
      death receptor CD95, cytochrome c not only translocates into the cytosol, but
      furthermore can be abundantly detected in the extracellular medium. The
      cytochrome c release from the cell is a rapid and apoptosis-specific process that
      occurred within 1 hour after induction of apoptosis, but not during necrosis.
      Interestingly, elevated cytochrome c levels were observed in sera from patients
      with hematologic malignancies. In the course of cancer chemotherapy, the serum
      levels of cytochrome c in the majority of the patients grew rapidly as a result
      of increased cell death. These data suggest that monitoring of cytochrome c in
      the serum of patients with tumors might serve as a useful clinical marker for the
      detection of the onset of apoptosis and cell turnover in vivo.

PMID- 11520806
TI  - Allelic loss on chromosome 4 (Lyr2/TLSR5) is associated with myeloid, B-lympho
      myeloid, and lymphoid (B and T) mouse radiation-induced leukemias.
AB  - The CBA/H mouse model of radiation-induced acute myeloid leukemia (AML) was re
      examined using molecular approaches. In addition to the typical promyelocytic
      AMLs, 34% were reclassified as early pre-B lympho-myeloid leukemias (L-ML) based
      on leukemic blood cell morphology, immunoglobulin heavy-chain gene re
      arrangements (IgH(R)), or expression of both lymphoid (Vpre-B1 and Rag1) and
      myeloid (myeloperoxidase and lysozyme M) genes. Allelic loss on chromosome 4 was
      frequently detected in AMLs (53%) and L-MLs (more than 95%), and the preferential
      loss of the maternally transmitted allele suggests the locus may be imprinted. A
      minimally deleted region (MDR) maps to a 3.4-cM interval, which is frequently
      deleted in radiation-induced thymic lymphomas (TLSR5) and contains a recessive,
      maternally transmitted genetic locus (Lyr2) that confers resistance to
      spontaneous and radiation-induced pre-B and T cell lymphomas, suggesting they are
      one and the same. Thus, the Lyr2/TLSR5 locus is frequently implicated in myeloid,
      lymphoid (B and T), and mixed-lineage mouse leukemias and lymphomas. Epigenetic
      inactivation of one Lyr2/TLSR5 allele during normal mouse development suggests
      that only a single hit is required for its inactivation during leukemogenesis,
      and this may be a significant contributing factor to the efficiency of the
      leukemogenic process in the mouse.

PMID- 11520807
TI  - Detection of N-Ras codon 61 mutations in subpopulations of tumor cells in
      multiple myeloma at presentation.
AB  - Activating point mutations in codons 12, 13, or 61 of the K-ras and N-ras genes
      have been reported to occur in up to 40% of patients with multiple myeloma at
      presentation. In a study of 34 presentation myeloma cases using a sensitive
      polymerase chain reaction-restriction fragment length polymorphism strategy on
      enriched tumor cell populations, the present study detected N-ras codon 61
      mutation-positive cells in all patients. Quantitative plaque hybridization using
      allele-specific oligonucleotide probes showed that in the majority of patients,
      ras mutation-positive cells comprise only a subpopulation of the total malignant
      plasma cell compartment (range, 12%-100%). Using clonospecific point mutations in
      the 5' untranslated region of the BCL6 gene to quantitate clonal B cells in FACS
      sorted bone marrow populations from 2 patients, the representation of ras
      mutation-positive cells was independent of immunophenotype. These observations
      imply that mutational activation of N-ras codon 61 is a mandatory event in the
      pathogenesis of multiple myeloma; such mutations provide a marker of intraclonal
      heterogeneity that may originate at an earlier ontologic stage than
      immunophenotypic diversification of the malignant B cell clone.

PMID- 11520808
TI  - A proteolytically truncated form of free CD18, the common chain of leukocyte
      integrins, as a novel marker of activated myeloid cells.
AB  - An unusual CD18 monoclonal antibody (mAb) MEM-148 binds, in contrast to standard
      CD18 mAbs, specifically to peripheral blood monocytes and neutrophils activated
      by various stimuli such as phorbol myristate acetate, opsonized zymosan, heat
      aggregated immunoglobulin, and (after priming with lipopolysaccharide, tumor
      necrosis factor, or granulocyte-macrophage colony-stimulating factor) also by
      formyl-methionyl-leucyl-phenylalanine. In addition, in vivo activated neutrophils
      obtained from urine of patients following recent prostatectomy were also strongly
      positive for MEM-148. On the activated myeloid cells the mAb recognized a 65- to
      70-kd protein identified immunochemically and by mass spectrometric peptide
      sequencing as a membrane-anchored fragment of CD18 (the common chain of leukocyte
      integrins) produced by proteolytic cleavage. The CD18 fragment originated mainly
      from integrin molecules stored intracellularly in resting cells, it was
      unassociated with CD11 chains, and its formation was inhibited by several types
      of protease inhibitors. Thus, the 65- to 70-kd CD18 fragment represents a novel
      abundant activation marker of myeloid cells of so far unknown function but
      possibly involved in conformational changes in leukocyte integrin molecules
      resulting in increased affinity to their ligands.

PMID- 11520809
TI  - Cell surface tissue transglutaminase is involved in adhesion and migration of
      monocytic cells on fibronectin.
AB  - Expression of tissue transglutaminase (transglutaminase II, tTG) was shown to
      increase drastically during monocyte differentiation into macrophages; however,
      its role in monocytic cells remains largely unknown. This study describes a novel
      function of cell surface tTG as an adhesion and migration receptor for
      fibronectin (Fn). Two structurally related transglutaminases, tTG and the A
      subunit of factor XIII (FXIIIA), are expressed on the surface of monocytic cells,
      whereas only surface tTG is associated with multiple integrins of the beta1 and
      beta3 subfamilies. Both surface levels of tTG and the amounts of integrin-bound
      tTG are sharply up-regulated during the conversion of monocytes into macrophages.
      In contrast, a reduction in biosynthesis and surface expression of FXIIIA
      accompanies monocyte differentiation. Cell surface tTG is colocalized with beta1-
      and beta3-integrins in podosomelike adhesive structures of macrophages adherent
      on Fn. Down-regulation of surface tTG by expression of antisense tTG construct or
      its inhibition by function-blocking antibodies significantly decreases adhesion
      and spreading of monocytic cells on Fn and, in particular, on the gelatin-binding
      fragment of Fn consisting of modules I6II1,2I7-9. Likewise, interfering with the
      adhesive function of surface tTG markedly reduces migration of myeloid cells on
      Fn and its gelatin-binding fragment. These data demonstrate that cell surface tTG
      serves as an integrin-associated adhesion receptor that might be involved in
      extravasation and migration of monocytic cells into tissues containing Fn
      matrices during inflammation.

PMID- 11520810
TI  - Short survival of phosphatidylserine-exposing red blood cells in murine sickle
      cell anemia.
AB  - Several transgenic murine models for sickle cell anemia have been developed that
      closely reproduce the biochemical and physiological disorders in the human
      disease. A comprehensive characterization is described of hematologic parameters
      of mature red blood cells, reticulocytes, and red cell precursors in the bone
      marrow and spleen of a murine sickle cell model in which erythroid cells
      expressed exclusively human alpha, gamma, and betaS globin. Red cell survival was
      dramatically decreased in these anemic animals, partially compensated by
      considerable enhancement in erythropoietic activity. As in humans, these murine
      sickle cells contain a subpopulation of phosphatidylserine-exposing cells that
      may play a role in their premature removal. Continuous in vivo generation of this
      phosphatidylserine-exposing subset may have a significant impact on the
      pathophysiology of sickle cell disease.

PMID- 11520811
TI  - Genomic analysis of clinical samples with serologic ABO blood grouping
      discrepancies: identification of 15 novel A and B subgroup alleles.
AB  - Since the cloning in 1990 of complementary DNA corresponding to messenger RNA
      transcribed at the blood group ABO locus, polymorphisms and phenotype-genotype
      correlations have been reported by several investigators. Exons 6 and 7,
      constituting 77% of the gene, have been analyzed previously in samples with
      variant phenotypes but for many subgroups the molecular basis remains unknown.
      This study analyzed 324 blood samples involved in ABO grouping discrepancies and
      determined their ABO genotype. Samples from individuals found to have known
      subgroup alleles (n = 53), acquired ABO phenotypes associated with different
      medical conditions (n = 65), probable chimerism (n = 3), and common red blood
      cell phenotypes (n = 109) were evaluated by ABO genotype screening only. Other
      samples (n = 94) from apparently healthy donors with weak expression of A or B
      antigens were considered potential subgroup samples without known molecular
      background. The full coding region (exons 1-7) and 2 proposed regulatory regions
      of the ABO gene were sequenced in selected A (n = 22) or B (n = 12) subgroup
      samples. Fifteen novel ABO subgroup alleles were identified, 2 of which are the
      first examples of mutations outside exon 7 associated with weak subgroups. Each
      allele was characterized by a missense or nonsense mutation for which screening
      by allele-specific primer polymerase chain reaction was performed. The novel
      mutations were encountered in 28 of the remaining 60 A and B subgroup samples but
      not among normal donors. As a result of this study, the number of definable
      alleles associated with weak ABO subgroups has increased from the 14 previously
      published to 29.

PMID- 11520812
TI  - Interferon-gamma and interleukin-6 gene polymorphisms associate with graft-versus
      host disease in HLA-matched sibling bone marrow transplantation.
AB  - Proinflammatory cytokines including interferon-gamma (IFNgamma), interleukin-6
      (IL-6), and tumor necrosis factor-alpha (TNFalpha) are implicated in the
      pathogenesis of acute graft-versus-host disease (aGVHD). Cytokine gene
      polymorphism is associated with functional differences in cytokine regulation and
      altered clinical performance in a variety of diseases. Polymorphism in the
      IFNgammaIntron1 microsatellite (CA)n repeat has been linked with in vitro
      IFNgamma production and renal transplant rejection. The IL-6(-174)(G/C) single
      nucleotide polymorphism has been linked to in vitro and in vivo IL-6 production,
      juvenile chronic arthritis, and renal transplant rejection. This study examined
      the potential association of GVHD with IFNgamma and IL-6 polymorphisms in 80
      sibling bone marrow transplant (BMT) donor/recipient pairs. Patients homozygous
      for the IFNgammaIntron1 allele 3 had more severe (grade III-IV) aGVHD. Patients
      possessing the IL-6(-174)G allele had a trend toward higher grades of aGVHD, and
      those homozygous for the IL-6(-174)G allele were more likely to develop chronic
      GVHD (cGVHD). The associations of previously identified aGVHD severity-associated
      cytokine gene polymorphisms (TNFd and IL-10(-1064)) with severe aGVHD were
      reconfirmed. Logistic regression analysis confirmed the association of severe
      aGVHD with recipient genotype at IFNgammaIntron1 (odds ratio [OR] 3.92; P =.02),
      IL-10(-1064) (OR 4.61; P =.026) and TNFd (OR 3.29; P =.039), and that of cGVHD
      with recipient IL-6(-174) genotype (OR 4.25; P =.007), in addition to age, gender
      mismatch, and underlying disease. Assessment of cytokine genotype may potentially
      allow more accurate prediction of GVHD and appropriate adjustment of GVHD
      prophylaxis, as well as indicating novel areas for future studies of GVHD
      pathogenesis.

PMID- 11520813
TI  - Radiosensitivity of thymic interleukin-7 production and thymopoiesis after bone
      marrow transplantation.
AB  - Interleukin-7 (IL-7) is the major thymopoietic cytokine. Injections of IL-7 after
      murine bone marrow transplantation (BMT) correct defects in thymic
      differentiation, including thymic hypocellularity, abnormal differentiation of
      CD3- CD4- CD8- (triple-negative [TN]) thymocytes into CD4+ CD8+ (double-positive
      [DP]) cells, and antigen-specific mature T-lymphocyte proliferation. To determine
      whether IL-7 production is decreased in BMT recipients, BMT was performed with
      congenic murine donor-recipient strains and escalating doses of pre-BMT
      conditioning. Increasing doses of radiation resulted in decreased thymic
      cellularity and maturation from the TN to the DP stage. Quantitative reverse
      transcription-polymerase chain reaction analyses demonstrated that intrathymic
      production of IL-7 was significantly decreased in irradiated mice than in
      nonirradiated controls. Decline in IL-7 transcript levels was correlated with the
      dose of radiation administered. Analyses of the numbers of CD45- major
      histocompatibility complex class II+ thymic stromal cells suggested that the
      mechanism for the decreased IL-7 production was loss of IL-7-producing thymic
      stromal cells. Experiments indicated that pre-BMT conditioning with radiation led
      to decreased stromal production of IL-7 and consequent blocks in the maturation
      of thymocytes. They provided a mechanism for both the abnormal thymopoiesis
      observed after BMT and the previously observed beneficial effects of IL-7
      administration in murine models. Impaired production of IL-7 by thymic stroma may
      be a general model for the clinically observed adverse effects of cytotoxic
      therapy on thymopoiesis.

PMID- 11520814
TI  - Targeting Janus kinase 3 to attenuate the severity of acute graft-versus-host
      disease across the major histocompatibility barrier in mice.
AB  - To prevent the development of acute graft-versus-host disease (GVHD) in lethally
      irradiated C57BL/6 (H-2b) recipient mice transplanted with bone marrow-splenocyte
      grafts from major histocompatibility complex (MHC) disparate BALB/c mice (H-2d),
      recipient mice were treated with the rationally designed JAK3 inhibitor WHI-P131
      [4-(4'-hydroxyphenyl)-amino-6,7-dimethoxyquinazoline] (20 mg/kg, 3 times a day
      [tid]) daily from the day of bone marrow transplantation (BMT) until the end of
      the 85-day observation period. Total body irradiation (TBI)-conditioned, vehicle
      treated control C57BL/6 mice (n = 38) receiving bone marrow-splenocyte grafts
      from BALB/c mice survived acute TBI toxicity, but they all developed
      histologically confirmed severe multi-organ GVHD and died after a median survival
      time of 37 days. WHI-P131 treatment (20 mg/kg intraperitoneally, tid) prolonged
      the median survival time of the BMT recipients to 56 days. The probability of
      survival at 2 months after BMT was 11% +/- 5% for vehicle-treated control mice (n
      = 38) and 41% +/- 9% for mice treated with WHI-P131 (n = 32) (P <.0001). Notably,
      the combination regimen WHI-P131 plus the standard anti-GVHD drug methotrexate
      (MTX) (10 mg/m2 per day) was more effective than WHI-P131 or MTX alone. More than
      half the C57BL/6 recipients receiving this most effective GVHD prophylaxis
      remained alive and healthy throughout the 85-day observation period, with a
      cumulative survival probability of 70% +/- 10%. Taken together, these results
      indicate that targeting JAK3 in alloreactive donor lymphocytes with a chemical
      inhibitor such as WHI-P131 may attenuate the severity of GVHD after BMT.

PMID- 11520816
TI  - Vgamma2Vdelta2 T-cell receptor-mediated recognition of aminobisphosphonates.
AB  - Aminobisphosphonates, potent derivatives of bisphosphonates, are frequently used
      for the treatment of conditions such as osteoporosis and bone metastases that are
      characterized by excessive osteoclastic bone resorption. Using T-cell receptor
      (TCR) transfer studies, we show that recognition of antigenic
      aminobisphosphonates that are known to stimulate human gammadelta T cells in
      vitro and in vivo (potency: risedronate > alendronate > pamidronate) requires
      expression of the Vgamma2Vdelta2 TCR and is thus Vgamma2Vdelta2 TCR-dependent.
      Myeloma cells or monocytes pulsed with risedronate and then washed rendered these
      target cells sensitive to lysis by a Vgamma2Vdelta2 T-cell clone or cell line.
      These results suggest that Vgamma2Vdelta2 TCR-dependent recognition leading to
      direct cytolysis of aminobisphosphonate-sensitized osteoclast or tumor targets
      may be a mechanism whereby aminobisphosphonate treatment of cancers metastatic to
      bone decreases osteoclastic activity and tumor burden and also may account for
      the decreased osteoclastic activity associated with successful treatment of
      osteoporosis.

PMID- 11520815
TI  - Increased risk of deep-vein thrombosis in patients with multiple myeloma
      receiving thalidomide and chemotherapy.
AB  - The occurrence of deep-vein thrombosis (DVT) in patients with newly diagnosed
      multiple myeloma, who were randomly assigned to receive identical induction
      chemotherapy with or without thalidomide, are reported in this study. The 2 study
      arms were comparable with respect to key myeloma prognostic factors and known
      risk factors for DVT. One hundred patients received induction chemotherapy
      including 4 cycles of continuous infusion of combinations of dexamethasone,
      vincristine, doxorubicin, cyclophosphamide, etoposide, and cisplatin, and each
      patient completed at least one induction cycle. DVT developed in 14 of 50
      patients (28%) randomly assigned to receive thalidomide but in only 2 of 50
      patients (4%) not given the agent (P =.002). All episodes of DVT occurred during
      the first 3 cycles of induction. Administration of thalidomide was resumed safely
      in 75% of patients receiving anticoagulation therapy. Thus, thalidomide given in
      combination with multiagent chemotherapy and dexamethasone is associated with a
      significantly increased risk of DVT, which appears to be safely treated with
      anticoagulation and does not necessarily warrant discontinuation of thalidomide.

PMID- 11520817
TI  - Differential inhibition of adenosine diphosphate- versus thrombin receptor
      activating peptide-stimulated platelet fibrinogen binding by abciximab due to
      different glycoprotein IIb/IIIa activation kinetics.
AB  - The exposure of internal glycoprotein (GP) IIb/IIIa receptors has been proposed
      to explain the incomplete inhibition of aggregation of thrombin receptor
      activating peptide (TRAP)-stimulated platelets by abciximab. However, a marked
      and rapid externalization of GPIIb/IIIa was also observed upon stimulation with
      30 microM adenosine diphosphate (ADP). ADP-induced fibrinogen binding was
      completely inhibited by 10 microg/mL abciximab, 30 nM tirofiban, or 3 microg/mL
      eptifibatide, while fibrinogen binding induced by 100 microM TRAP was inhibited
      only by 50%. Interestingly, striking differences in fibrinogen binding kinetics
      in ADP- versus TRAP-stimulated platelets were observed. ADP-induced fibrinogen
      binding was much slower than that of abciximab. These differences in the
      fibrinogen binding rate were due to differential GPIIb/IIIa activation kinetics
      because the actual fibrinogen binding rate (measured by adding fibrinogen after
      platelet activation) was similar in ADP- and TRAP-stimulated platelets. Thus, the
      TRAP-induced GPIIb/IIIa activation rate would allow significant amounts of
      fibrinogen to occupy externalized GPIIb/IIIa receptors even in the presence of
      the inhibitor.

PMID- 11520818
TI  - Immunomodulatory effects of extracorporeal photochemotherapy in patients with
      extensive chronic graft-versus-host disease.
AB  - Extracorporeal photochemotherapy (ECP) has been associated with clinical
      improvement in several patients with acute and chronic graft-versus-host disease
      (cGVHD) after allogeneic bone marrow transplantation, but the mechanism of action
      is unknown. This study tested the hypothesis that in patients with cGVHD, ECP
      modulates alloreactivity by affecting activated lymphocyte populations or by
      altering the interaction between effector lymphocytes and antigen-presenting
      cells (APCs). Ten patients who had refractory cGVHD were treated with ECP, and
      the clinical response to and immunologic effects of this therapy were assessed.
      Seven patients had a response and 3 had no change in clinical manifestations of
      cGVHD. One patient died from catheter-related sepsis. Immunologic effects
      observed after ECP included normalization of inverted ratios of CD4 to CD8 cells,
      an increase in the number of CD3-CD56+ natural killer (NK) cells, and a decrease
      in CD80+ and CD123+ circulating dendritic cells. The results suggest that ECP
      modulates both NK cells and APC populations in patients with cGVHD.

PMID- 11520819
TI  - Doctoring deprived areas.

PMID- 11520820
TI  - The challenge of looking after people with dementia.

PMID- 11520821
TI  - Hand hygiene.

PMID- 11520822
TI  - The non-invasive diagnosis of pulmonary embolus.

PMID- 11520823
TI  - Patients and medical power.

PMID- 11520824
TI  - US consumer groups allege misleading drug claims.

PMID- 11520825
TI  - Bayer faces potential fine over cholesterol lowering drug.

PMID- 11520827
TI  - Woman fights for right to die with dignity.

PMID- 11520828
TI  - Drugs for malaria and psychosis may offer hope to people with CJD.

PMID- 11520829
TI  - Condom use seems to be reducing number of new HIV/AIDS cases.

PMID- 11520830
TI  - Rate of decline in US AIDS cases is slowing.

PMID- 11520831
TI  - Israeli minister orders hepatitis B vaccine for survivors of suicide bomb
      attacks.

PMID- 11520836
TI  - Treatment of Indian visceral leishmaniasis with single or daily infusions of low
      dose liposomal amphotericin B: randomised trial.
AB  - OBJECTIVE: To test short course, low dose liposomal amphotericin B as single or
      daily infusion treatment in Indian visceral leishmaniasis (kala-azar). DESIGN:
      Randomised, open label study. SETTING: Inpatient unit for leishmaniasis in Bihar,
      India. PARTICIPANTS: 91 adults and children with splenic aspirate positive for
      infection. INTERVENTIONS: Total dose of 5 mg/kg of liposomal amphotericin B given
      as a single infusion (n=46) or as once daily infusions of 1 mg/kg for five days
      (n=45). MAIN OUTCOME MEASURES: Clinical and parasitological cure assessed 14 days
      after treatment and long term definitive cure (healthy, no relapse) at six
      months. RESULTS: All but one person in each group had an initial apparent cure.
      During six months of follow up, three patients in the single dose group and two
      in the five dose group relapsed. Complete response (definitive cure) was
      therefore achieved in 84 of 91 subjects (92%): 42 of 46 patients in the single
      dose group (91%, 95% confidence interval 79% to 98%) and 42 of 45 in the five
      dose group (93%, 82% to 99%). Response rates in the two groups were not
      significantly different. CONCLUSION: Low dose liposomal amphotericin B (5 mg/kg),
      given either as a five day course or as a single infusion, seems to be effective
      for visceral leishmaniasis and warrants further testing.

PMID- 11520837
TI  - Screening for Down's syndrome: effects, safety, and cost effectiveness of first
      and second trimester strategies.
AB  - OBJECTIVE: To compare the effects, safety, and cost effectiveness of antenatal
      screening strategies for Down's syndrome. DESIGN: Analysis of incremental cost
      effectiveness. SETTING: United Kingdom. MAIN OUTCOME MEASURES: Number of liveborn
      babies with Down's syndrome, miscarriages due to chorionic villus sampling or
      amniocentesis, health care costs of screening programme, and additional costs and
      additional miscarriages per additional affected live birth prevented by adopting
      a more effective strategy. RESULTS: Compared with no screening, the additional
      cost per additional liveborn baby with Down's syndrome prevented was 22 000 pound
      sterling for measurement of nuchal translucency. The cost of the integrated test
      was 51 000 pound sterling compared with measurement of nuchal translucency. All
      other strategies were more costly and less effective, or cost more per additional
      affected baby prevented. Depending on the cost of the screening test, the first
      trimester combined test and the quadruple test would also be cost effective
      options. CONCLUSIONS: The choice of screening strategy should be between the
      integrated test, first trimester combined test, quadruple test, or nuchal
      translucency measurement depending on how much service providers are willing to
      pay, the total budget available, and values on safety. Screening based on
      maternal age, the second trimester double test, and the first trimester serum
      test was less effective, less safe, and more costly than these four options.

PMID- 11520838
TI  - Quality of care in private sector and NHS facilities for people with dementia:
      cross sectional survey.

PMID- 11520839
TI  - Prescriptions with potential drug interactions dispensed at Swedish pharmacies in
      January 1999: cross sectional study.

PMID- 11520840
TI  - Rationing in the NHS: audit of outcome and acceptance of restriction criteria for
      minor operations.

PMID- 11520841
TI  - Cohort survey of heart valve replacement patients: does the valve card scheme
      have room for improvement?

PMID- 11520842
TI  - Childhood deaths from acute appendicitis in England and Wales 1963-97:
      observational population based study.

PMID- 11520844
TI  - Qualitative study of pilot payment aimed at increasing general practitioners'
      antismoking advice to smokers.
AB  - OBJECTIVES: To elicit general practitioners' and practice nurses' accounts of
      changes in their clinical practice or practice organisation made to claim a pilot
      health promotion payment. To describe attitudes towards the piloted and previous
      health promotion payments. DESIGN: Qualitative, semistructured interview study.
      SETTING: 13 general practices in Leicester. PARTICIPANTS: 18 general
      practitioners and 13 practice nurses. RESULTS: Health professionals did not
      report substantially changing their clinical practice to claim the new payments
      and made only minimal changes in practice organisation. The new health promotion
      payment did not overcome general practitioners' resistance towards raising the
      issue of smoking when they felt that doing so could cause confrontation with
      patients. General practitioners who made the largest number of claims altered the
      way in which they recorded patients' smoking status rather than raising the topic
      of smoking more frequently with patients. PARTICIPANTS had strong negative views
      on the new payment, feeling it would also be viewed negatively by patients. They
      were, however, more positive about health promotion payments that rewarded
      "extra" effort-for example, setting up practice based smoking cessation clinics.
      CONCLUSIONS: General practitioners and practice nurses were negative about a new
      health promotion payment, despite agreeing to pilot it. Health promotion payments
      do not automatically generate effective health promotion activity, and
      policymakers should consider careful piloting and evaluation of future changes in
      health promotion payments.

PMID- 11520845
TI  - Intervention study to evaluate pilot health promotion payment aimed at increasing
      general practitioners' antismoking advice to smokers.

PMID- 11520846
TI  - Extracts from "clinical evidence": Infantile colic.

PMID- 11520848
TI  - Monitoring clinical trials--interim data should be publicly available.

PMID- 11520849
TI  - Regulating nursing homes: The challenge of regulating care for older people in
      Australia.

PMID- 11520850
TI  - Statistics notes: Concealing treatment allocation in randomised trials.

PMID- 11520852
TI  - Screening for type 2 diabetes. Undiagnosed diabetes must be detected.

PMID- 11520855
TI  - Cell cycle-dependent recruitment of HDAC-1 correlates with deacetylation of
      histone H4 on an Rb-E2F target promoter.
AB  - The transcription factor E2F, which is a key element in the control of cell
      proliferation, is repressed by Rb and other pocket proteins in growth-arrested
      differentiating cells, as well as in proliferating cells when they progress
      through early G1. It is not known whether similar mechanisms are operative in the
      two situations. A body of data suggests that E2F repression by pocket proteins
      involves class I histone deacetylases (HDACs). It has been hypothesized that
      these enzymes are recruited to E2F target promoters where they deacetylate
      histones. Here we have tested this hypothesis directly by using formaldehyde
      cross-linked chromatin immunoprecipitation (XChIP) assays to evaluate HDAC
      association in living cells. Our data show that a histone deacetylase, HDAC-1, is
      stably bound to an E2F target promoter during early G1 in proliferating cells and
      released at the G1-S transition. In addition, our results reveal an inverse
      correlation between HDAC-1 recruitment and histone H4 acetylation on specific
      lysines.

PMID- 11520856
TI  - Restoration of telomerase activity rescues chromosomal instability and premature
      aging in Terc-/- mice with short telomeres.
AB  - Reconstitution of telomerase activity is proposed as a potential gene therapy to
      prevent, or rescue, age-related diseases produced by critical telomere
      shortening. However, it is not known whether or not short telomeres are
      irreversibly damaged. We addressed this by re-introducing telomerase in late
      generation telomerase-deficient mice, Terc-/-, which have short telomeres and
      show severe proliferative defects. For this, we have crossed these mice with
      Terc+/- mice and analyzed telomere length, chromosomal instability and premature
      aging of the progeny. The Terc-/- progeny had one set of chromosomes with normal
      telomeres, whereas the other set remained with critically short telomeres; these
      mice presented chromosomal instability and premature aging. In contrast, Terc+/-
      progeny showed all chromosomes with detectable telomeres, and did not show
      chromosomal instability or premature aging. These results prove that critically
      short telomeres can be rescued by telomerase, and become fully functional, thus
      rescuing premature aging. This has important implications for the future design
      of telomerase-based gene therapy of age-related diseases.

PMID- 11520857
TI  - Converting MlyI endonuclease into a nicking enzyme by changing its
      oligomerization state.
AB  - N.BstNBI is a nicking endonuclease that recognizes the sequence GAGTC and nicks
      one DNA strand specifically. The Type IIs endonuclease, MlyI, also recognizes
      GAGTC, but cleaves both DNA strands. Sequence comparisons revealed significant
      similarities between N.BstNBI and MlyI. Previous studies showed that MlyI
      dimerizes in the presence of a cognate DNA, whereas N.BstNBI remains a monomer.
      This suggests that dimerization may be required for double-stranded cleavage. To
      test this hypothesis, we used a multiple alignment to design mutations to disrupt
      the dimerization function of MlyI. When Tyr491 and Lys494 were both changed to
      alanine, the mutated endonuclease, N.MlyI, no longer formed a dimer and cleaved
      only one DNA strand specifically. Thus, we have shown that changing the
      oligomerization state of an enzyme changes its enzymatic function. This
      experiment also established a protocol that could be applied to other Type IIs
      endonucleases in order to generate more novel nicking endonucleases.

PMID- 11520858
TI  - Impact of the six nucleotides downstream of the stop codon on translation
      termination.
AB  - The efficiency of translation termination is influenced by local contexts
      surrounding stop codons. In Saccharomyces cerevisiae, upstream and downstream
      sequences act synergistically to influence the translation termination
      efficiency. By analysing derivatives of a leaky stop codon context, we initially
      demonstrated that at least six nucleotides after the stop codon are a key
      determinant of readthrough efficiency in S. cerevisiae. We then developed a
      combinatorial-based strategy to identify poor 3' termination contexts. By
      screening a degenerate oligonucleotide library, we identified a consensus
      sequence -CA(A/G)N(U/C/G)A-, which promotes >5% readthrough efficiency when
      located downstream of a UAG stop codon. Potential base pairing between this
      stimulatory motif and regions close to helix 18 and 44 of the 18S rRNA provides a
      model for the effect of the 3' stop codon context on translation termination.

PMID- 11520859
TI  - Extracellular signal regulated kinase 5 (ERK5) is required for the
      differentiation of muscle cells.
AB  - Extracellular signal regulated kinase 5 (ERK5) is a novel member of the mitogen
      activated protein kinase (MAPK) family with a poorly defined physiological
      function. Since ERK5 and its upstream activator MEK5 are abundant in skeletal
      muscle we examined a function of the cascade during muscle differentiation. We
      show that ERK5 is activated upon induction of differentiation in mouse myoblasts
      and that selective activation of the pathway results in promoter activation of
      differentiation-specific genes. Moreover, myogenic differentiation is completely
      blocked when ERK5 expression is inhibited by antisense RNA. Thus, we conclude
      that the MEK5/ERK5 MAP kinase cascade is critical for early steps of muscle cell
      differentiation.

PMID- 11520860
TI  - A novel muscle LIM-only protein is generated from the paxillin gene locus in
      Drosophila.
AB  - Paxillin is a protein containing four LIM domains, and functions in integrin
      signaling. We report here that two transcripts are generated from the paxillin
      gene locus in Drosophila; one encodes a protein homolog of the vertebrate
      Paxillin (DPxn37), and the other a protein with only three LIM domains, partly
      encoded by its own specific exon (PDLP). At the myotendinous junctions of
      Drosophila embryos where integrins play important roles, both DPxn37 and PDLP are
      highly expressed with different patterns; DPxn37 is predominantly concentrated at
      the center of the junctions, whereas PDLP is highly enriched at neighboring sides
      of the junction centers, primarily expressed in the mesodermal myotubes. Northern
      blot analysis revealed that DPxn37 is ubiquitously expressed throughout the life
      cycle, whereas PDLP expression exhibits a biphasic pattern during development,
      largely concomitant with muscle generation and remodeling. Our results
      collectively reveal that a unique system exists in Drosophila for the generation
      of a novel type of LIM-only protein, highly expressed in the embryonic
      musculature, largely utilizing the Paxillin LIM domains.

PMID- 11520862
TI  - Stored proteinases and the initiation of storage protein mobilization in seeds
      during germination and seedling growth.
AB  - Though endopeptidases and carboxypeptidases are present in protein bodies of dry
      quiescent seeds the function of these proteases during germination is still a
      matter of debate. In some plants it was demonstrated that endopeptidases of dry
      protein bodies degrade storage proteins of these organelles. Other studies
      describe cases where this did not happen. The role that stored proteinases play
      in the initiation of storage protein breakdown in germinating seeds thus remains
      unclear. Numerous reviews state that the initiation of reserve protein
      mobilization is attributed to de novo formed endopeptidases which together with
      stored carboxypeptidases degrade the bulk of proteins in storage organs and
      tissues after seeds have germinated. The evidence that the small amounts of
      endopeptidases in protein bodies of embryonic axes and cotyledons of dry seeds
      from dicotyledonous plants play an important role in the initiation of storage
      protein mobilization during early germination is summarized here.

PMID- 11520861
TI  - Presenilin-dependent gamma-secretase processing of beta-amyloid precursor protein
      at a site corresponding to the S3 cleavage of Notch.
AB  - The presenilin (PS)-dependent site 3 (S3) cleavage of Notch liberates its
      intracellular domain (NICD), which is required for Notch signaling. The similar
      gamma-secretase cleavage of the beta-amyloid precursor protein (betaAPP) results
      in the secretion of amyloid beta-peptide (Abeta). However, little is known about
      the corresponding C-terminal cleavage product (CTFgamma). We have now identified
      CTFgamma in brain tissue, in living cells, as well as in an in vitro system.
      Generation of CTFgamma is facilitated by PSs, since a dominant-negative mutation
      of PS as well as a PS gene knock out prevents its production. Moreover, gamma
      secretase inhibitors, including one that is known to bind to PS, also block
      CTFgamma generation. Sequence analysis revealed that CTFgamma is produced by a
      novel gamma-secretase cut, which occurs at a site corresponding to the S3
      cleavage of Notch.

PMID- 11520863
TI  - Antisense-transformation reveals novel roles for class I beta-1,3-glucanase in
      tobacco seed after-ripening and photodormancy.
AB  - Little is known about the molecular basis for seed dormancy, after-ripening, and
      radicle emergence through the covering layers during germination. In tobacco,
      endosperm rupture occurs after testa rupture and is the limiting step in seed
      germination. Class I beta-1,3-glucanase (betaGLU I), which is induced in the
      micropylar endosperm just prior to its penetration by the radicle, is believed to
      help weaken the endosperm wall. Evidence is presented here for a second site of
      betaGLU I action during after-ripening. Tobacco plants were transformed with
      antisense betaGLU I constructs with promoters thought to direct endosperm
      specific expression. Unexpectedly, these transformants were unaffected in
      endosperm rupture and did not exhibit reduced betaGLU I expression during
      germination. Nevertheless, antisense betaGLU I transformation delayed the onset
      of testa rupture in light-imbibed, after-ripened seeds and inhibited the after
      ripening-mediated release of photodormancy. It is proposed that betaGLU I
      expression in the dry seed contributes to the after-ripening-mediated release of
      seed dormancy.

PMID- 11520864
TI  - The export of amino acid in the phloem is altered in wheat plants lacking the
      short arm of chromosome 7B.
AB  - Grain protein content is one of the major determinants of the baking and
      nutritional quality of wheat. It has previously been reported that the
      ditelosomic line of wheat (Triticum aestivum L.) CSDT7BL, where the short arm of
      chromosome 7B is missing, shows a lower grain protein concentration than the
      normal line, but a similar grain yield. In the present paper the growth and
      nitrogen (N) metabolism of wheat plants cv. Chinese Spring (CS) and its
      ditelosomic line CSDT7BL were compared. When plants were grown to maturity in
      pots with different N supplements, the wild-type line showed a higher grain
      protein concentration and a lower straw N concentration than the ditelosomic line
      at every N level analysed, suggesting a deficiency in the N remobilization
      capacity. When 15-d-old plants were grown in a growth cabinet in pots with sand,
      and supplied with nutrient solutions of different nitrate concentrations, the
      ditelosomic line showed no differences in N uptake per unit of root dry weight,
      nitrate reductase activity, nitrate, total N concentration or free amino acid
      concentration. However, the ditelosomic line showed a decreased capacity to
      export amino acids in the phloem under high N, independently of the N source.
      This deficiency was also observed under dark-induced senescence. The diminished
      export of amino acids to the phloem was principally caused by a decrease in the
      export of Glu, Asp, and Gln. It is suggested that the decrease in grain protein
      concentration in the ditelosomic line is a consequence of defective export in the
      phloem of these amino acids.

PMID- 11520865
TI  - Comparative study of the O(2), CO(2) and temperature effect on respiration
      between "Conference" pear cell protoplasts in suspension and intact pears.
AB  - The influence of the O(2) and CO(2) concentration and the temperature on the O(2)
      uptake rate of cool-stored intact pears and pear cell protoplasts in suspension
      was compared. Protocols to isolate pear cell protoplasts from pear tissue and two
      methods to measure protoplast respiration have been developed. Modified Michaelis
      Menten kinetics were applied to describe the effect of the O(2) and the CO(2)
      concentration on the O(2) uptake rate and temperature dependence was analysed
      with an Arrhenius equation. Both systems were described with a non-competitive
      type of CO(2) inhibition. Due to the inclusion of gas diffusion properties, the
      Michaelis-Menten constant for intact pears (2.5 mM) was significantly larger than
      the one for protoplasts in suspension (3 microM), which was in turn larger than
      the Michaelis-Menten constant obtained in mitochondrial respiration measurements
      described in the literature. It was calculated that only 3.6% of the total
      diffusion effect absorbed in the Michaelis-Menten constant for intact pears,
      could be attributed to intracellular gas diffusion. The number of cells per
      volume of tissue was counted microscopically to establish a relationship between
      the pear cell protoplast and intact pear O(2) uptake rate. A remarkable
      similarity was observed: values of 61.8 nmol kg(-1) s(-1) for protoplasts and
      87.1 nmol kg(-1) s(-1) for intact pears were obtained. Also, the inhibitory
      effect of CO(2) on the respiration rate was almost identical for protoplasts and
      intact pears, suggesting that protoplast suspensions are useful for the study of
      other aspects of the respiration metabolism.

PMID- 11520866
TI  - Small decreases in SBPase cause a linear decline in the apparent RuBP
      regeneration rate, but do not affect Rubisco carboxylation capacity.
AB  - The response of net photosynthetic CO(2) uptake (A) to increasing leaf
      intercellular CO(2) concentration (c(i)) was determined in antisense Nicotiana
      tabacum plants, derived from six independent transformation lines, displaying a
      range of sedoheptulose-1, 7-bisphosphatase (SBPase) activities. The maximum in
      vivo ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) carboxylation
      (V(c,max)) and RuBP regeneration (J(max)) rates were calculated from the steady
      state measurements of the A to c(i) response curves. In plants with reductions in
      SBPase activity of between 9% and 60%, maximum RuBP regeneration capacity
      declined linearly (r(2)=0.79) and no significant change in apparent in vivo
      Rubisco activity (V(c,max)) was observed in these plants. No correlation between
      V(c,max) and a decrease in capacity for RuBP regeneration was observed
      (r(2)=0.14) in the SBPase antisense plants. These data demonstrate that small
      decreases in SBPase activity limit photosynthetic carbon assimilation by reducing
      the capacity for RuBP regeneration.

PMID- 11520867
TI  - Single and double overexpression of C(4)-cycle genes had differential effects on
      the pattern of endogenous enzymes, attenuation of photorespiration and on
      contents of UV protectants in transgenic potato and tobacco plants.
AB  - To improve the efficiency of CO(2) fixation in C(3) photosynthesis, C(4)-cycle
      genes were overexpressed in potato and tobacco plants either individually or in
      combination. Overexpression of the phosphoenolpyruvate carboxylase (PEPC) gene
      (ppc) from Corynebacterium glutamicum (cppc) or from potato (stppc, deprived of
      the phosphorylation site) in potato resulted in a 3-6-fold induction of
      endogenous cytosolic NADP malic enzyme (ME) and an increase in the activities of
      NAD-ME (3-fold), NADP isocitrate dehydrogenase (ICDH), pyruvate kinase (PK), NADP
      glycerate-3-P dehydrogenase (NADP-GAPDH), and PEP phosphatase (PEPP). In double
      transformants overexpressing cppc and chloroplastic NADP-ME from Flaveria
      pringlei (fpMe1), cytosolic NADP-ME was less induced and pleiotropic effects were
      diminished. There were no changes in enzyme pattern in single fpMe1
      overexpressors. In cppc overexpressors of tobacco, the increase in endogenous
      cytosolic NADP-ME activity was small and changes in other enzymes were less
      pronounced. Determinations of the CO(2) compensation point (Gamma*) as well as
      temperature and oxygen effects on photosynthesis produced variational data
      suggesting that the desired decline in photorespiration occurred only under
      certain experimental conditions. Double transformants of potato (cppc/fpMe1)
      exhibited the most consistent attenuating effect on photorespiration. In
      contrast, photorespiration in tobacco plants appeared to be diminished most in
      single cppc overexpressors rather than in double transformants (cppc/fpMe1). In
      tobacco, introduction of the PEP carboxykinase (PEPCK) gene from the bacterium
      Sinorhizobium meliloti (pck) had little effect on photosynthetic parameters in
      single (pck) and double transformants (cppc/pck). In transgenic potato plants,
      increased PEPC activities resulted in a decline in UV protectants (flavonoids) in
      single cppc or stppc transformants, but not in double transformants (cppc/fpMe1).
      PEP provision to the shikimate pathway inside the plastids, from which flavonoids
      derive, might be restricted only in single PEPC overexpressors.

PMID- 11520868
TI  - Characterization of photosynthetic pigment composition, photosystem II
      photochemistry and thermal energy dissipation during leaf senescence of wheat
      plants grown in the field.
AB  - Photosynthetic pigment composition and photosystem II (PSII) photochemistry were
      characterized during the flag leaf senescence of wheat plants grown in the field.
      During leaf senescence, neoxanthin and beta-carotene decreased concomitantly with
      chlorophyll, whereas lutein and xanthophyll cycle pigments were less affected,
      leading to increases in lutein/chlorophyll and xanthophyll cycle
      pigments/chlorophyll ratios. The chlorophyll a/b ratio also increased. With the
      progression of senescence, the maximal efficiency of PSII photochemistry
      decreased only slightly in the early morning (low light conditions), but
      substantially at midday (high light conditions). Actual PSII efficiency,
      photochemical quenching and the efficiency of excitation capture by open PSII
      centres decreased significantly both early in the morning and at midday and such
      decreases were much greater at midday than in the early morning. At the same
      time, non-photochemical quenching, zeaxanthin and antheraxanthin contents at the
      expense of violaxanthin increased both early in the morning and at midday, with a
      greater increase at midday. The results in the present study suggest that a down
      regulation of PSII occurred in senescent leaves and that the xanthophyll cycle
      plays a role in the protection of PSII from photoinhibitory damage in senescent
      leaves by dissipating excess excitation energy, particularly when exposed to high
      light.

PMID- 11520869
TI  - Auxin herbicides induce H(2)O(2) overproduction and tissue damage in cleavers
      (Galium aparine L.).
AB  - The phytotoxic effects of auxin herbicides, including the quinoline carboxylic
      acids quinmerac and quinclorac, the benzoic acid dicamba and the pyridine
      carboxylic acid picloram, were studied in relation to changes in phytohormonal
      ethylene and abscisic acid (ABA) levels and the production of H(2)O(2) in
      cleavers (Galium aparine). When plants were root-treated with 10 microM
      quinmerac, ethylene synthesis was stimulated in the shoot tissue, accompanied by
      increases in immunoreactive levels of ABA and its precursor xanthoxal. It has
      been demonstrated that auxin herbicide-stimulated ethylene triggers ABA
      biosynthesis. The time-course and dose-response of ABA accumulation closely
      correlated with reductions in stomatal aperture and CO(2) assimilation and
      increased levels of hydrogen peroxide (H(2)O(2)), deoxyribonuclease (DNase)
      activity and chlorophyll loss. The latter parameters were used as sensitive
      indicators for the progression of tissue damage. On a shoot dry weight basis,
      DNase activity and H(2)O(2) levels increased up to 3-fold, relative to the
      control. Corresponding effects were obtained using auxin herbicides from the
      other chemical classes or when ABA was applied exogenously. It is hypothesized,
      that auxin herbicides stimulate H(2)O(2) generation which contributes to the
      induction of cell death in Galium leaves. This overproduction of H(2)O(2) could
      be triggered by the decline of photosynthetic activity, due to ABA-mediated
      stomatal closure.

PMID- 11520870
TI  - Trehalose metabolism in Arabidopsis: occurrence of trehalose and molecular
      cloning and characterization of trehalose-6-phosphate synthase homologues.
AB  - Axenically grown Arabidopsis thaliana plants were analysed for the occurrence of
      trehalose. Using gas chromatography-mass spectrometry (GC-MS) analysis, trehalose
      was unambiguously identified in extracts from Arabidopsis inflorescences. In a
      variety of organisms, the synthesis of trehalose is catalysed by trehalose-6
      phosphate synthase (TPS; EC 2.4.1.15) and trehalose-6-phosphate phosphatase (TPP;
      EC 3.1.3.12). Based on EST (expressed sequence tag) sequences, three full-length
      Arabidopsis cDNAs whose predicted protein sequences show extensive homologies to
      known TPS and TPP proteins were amplified by RACE-PCR. The expression of the
      corresponding genes, AtTPSA, AtTPSB and AtTPSC, and of the previously described
      TPS gene, AtTPS1, was analysed by quantitative RT-PCR. All of the genes were
      expressed in the rosette leaves, stems and flowers of Arabidopsis plants and, to
      a lower extent, in the roots. To study the role of the Arabidopsis genes, the
      AtTPSA and AtTPSC cDNAs were expressed in Saccharomyces cerevisiae mutants
      deficient in trehalose synthesis. In contrast to AtTPS1, expression of AtTPSA and
      AtTPSC in the tps1 mutant lacking TPS activity did not complement trehalose
      formation after heat shock or growth on glucose. In addition, no TPP function
      could be identified for AtTPSA and AtTPSC in complementation studies with the S.
      cerevisiae tps2 mutant lacking TPP activity. The results indicate that while
      AtTPS1 is involved in the formation of trehalose in Arabidopsis, some of the
      Arabidopsis genes with homologies to known TPS/TPP genes encode proteins lacking
      catalytic activity in trehalose synthesis.

PMID- 11520871
TI  - Are contents of Rubisco, soluble protein and nitrogen in flag leaves of rice
      controlled by the same genetics?
AB  - Genetic relations among the contents of Rubisco, soluble protein and total leaf
      nitrogen (N) in leaves of rice (Oryza sativa L.) were studied by quantitative
      trait loci (QTL) analysis with a population of backcross inbred lines (BILs) of
      japonica Nipponbarexindica Kasalath. The ratio of Rubisco to total leaf N in
      leaves is the main target in improving photosynthetic N-use efficiency in plants.
      QTLs controlling Rubisco content were not detected near QTLs for total leaf N
      content. These results indicate that contents of Rubisco and total leaf N are
      controlled by different genetics. QTLs that controlled the ratio of Rubisco to
      total leaf N (CORNs) were detected. These results suggest that some mechanism(s)
      may be involved in determining this ratio, while the contents of Rubisco and
      total leaf N are controlled in other ways. In elite BILs, the ratios of Rubisco
      to total leaf N were higher than those of both parents. These results suggest a
      good possibility of improving N-use efficiency by CORNs in cultivated rice. A QTL
      controlling Rubisco content was mapped near a QTL for soluble protein content on
      chromosome 8 at 5 d after heading and on chromosome 9 at 25 d. In each chromosome
      region, the peaks of both QTLs overlapped accurately, giving a high possibility
      of pleiotropic effects by the same genes. Different QTLs controlling soluble
      protein or Rubisco were detected from those detected at 5 d or 25 d after
      heading. This suggests that these traits are genetically controlled depending on
      the growth stages of leaves.

PMID- 11520872
TI  - Hydraulic conductivity of rice roots.
AB  - A pressure chamber and a root pressure probe technique have been used to measure
      hydraulic conductivities of rice roots (root Lp(r) per m(2) of root surface
      area). Young plants of two rice (Oryza sativa L.) varieties (an upland variety,
      cv. Azucena and a lowland variety, cv. IR64) were grown for 31-40 d in 12 h days
      with 500 micromol m(-2) s(-1) PAR and day/night temperatures of 27 degrees C and
      22 degrees C. Root Lp(r) was measured under conditions of steady-state and
      transient water flow. Different growth conditions (hydroponic and aeroponic
      culture) did not cause visible differences in root anatomy in either variety.
      Values of root Lp(r) obtained from hydraulic (hydrostatic) and osmotic water flow
      were of the order of 10(-8) m s(-1) MPa(-1) and were similar when using the
      different techniques. In comparison with other herbaceous species, rice roots
      tended to have a higher hydraulic resistance of the roots per unit root surface
      area. The data suggest that the low overall hydraulic conductivity of rice roots
      is caused by the existence of apoplastic barriers in the outer root parts
      (exodermis and sclerenchymatous (fibre) tissue) and by a strongly developed
      endodermis rather than by the existence of aerenchyma. According to the composite
      transport model of the root, the ability to adapt to higher transpirational
      demands from the shoot should be limited for rice because there were minimal
      changes in root Lp(r) depending on whether hydrostatic or osmotic forces were
      acting. It is concluded that this may be one of the reasons why rice suffers from
      water shortage in the shoot even in flooded fields.

PMID- 11520873
TI  - Differential expression of XET-related genes in the leaf elongation zone of F.
      pratensis.
AB  - Festuca pratensis Huds. is a forage grass with the ability to withstand harsh
      climatic conditions. However, its potential agronomic use is limited by its poor
      competitive ability, which can be traced to limitations in leaf growth. In order
      to characterize this process and to identify genes which might function as
      markers for leaf growth, three XET-related genes in the leaf elongation zone
      (LEZ) of F. pratensis are reported. A detailed expression analysis is presented
      of the three genes in two F. pratensis genotypes with contrasting leaf growth
      characteristics grown under two nitrogen levels. By means of a detailed spatial
      analysis of growth and XET encoding transcript pattern along the LEZ, a specific
      correlation is shown between FpXET1 expression and tissue elongation that is
      maintained under the different growth conditions, while the two other XETs
      expressed in the LEZ show different transcript dynamics. Tissue localization of
      FpXET1 and FpXET2 transcripts indicate an accumulation throughout young tissue,
      which is consistent with the encoded proteins playing roles in cell wall
      modification processes during growth. It is proposed that FpXET1 is a potential
      marker for tissue elongation and leaf growth in F. pratensis.

PMID- 11520874
TI  - QTL analysis of photosynthesis and water status traits in sunflower (Helianthus
      annuus L.) under greenhouse conditions.
AB  - The identification of QTL for several physiological traits in sunflower is
      described. Traits related to photosynthesis (leaf chlorophyll concentration, net
      photosynthesis and internal CO(2) concentration) and water status (stomatal
      conductance, transpiration, predawn leaf water potential, and relative water
      content) were evaluated in a population of recombinant inbred lines under
      greenhouse conditions. Narrow-sense heritabilities were low to average. Using an
      AFLP linkage map, 19 QTL were detected explaining 8.8-62.9% of the phenotypic
      variance for each trait. Among these, two major QTL for net photosynthesis were
      identified on linkage group IX. One QTL co-location was found on linkage group
      VIII for stomatal movements and water status. Coincident locations for QTL
      regulating photosynthesis, transpiration and leaf water potential were described
      on linkage group XIV. These results lead to the first description of the
      organization of genomic regions related to yield in sunflower.

PMID- 11520875
TI  - The relationship between photosystem II efficiency and quantum yield for CO(2)
      assimilation is not affected by nitrogen content in apple leaves.
AB  - Bench-grafted Fuji/M.26 apple (Malus domestica Borkh.) trees were fertigated with
      different concentrations of nitrogen by using a modified Hoagland's solution for
      45 d. CO(2) assimilation and photosystem II (PSII) quantum efficiency in response
      to incident photon flux density (PFD) were measured simultaneously in recent
      fully expanded leaves under low O(2) (2%) and saturated CO(2) (1300 micromol mol(
      1)) conditions. A single curvilinear relationship was found between true quantum
      yield for CO(2) assimilation and PSII quantum efficiency for leaves with a wide
      range of leaf N content. The relationship was linear up to a quantum yield of
      approximately 0.05 mol CO(2) mol(-1) quanta. It then became curvilinear with a
      further rise in quantum yield in response to decreasing PFD. This relationship
      was subsequently used as a calibration curve to assess the rate of non-cyclic
      electron transport associated with Rubisco and the partitioning of electron flow
      between CO(2) assimilation and photorespiration in different N leaves in response
      to intercellular CO(2) concentration (C(i)) under normal O(2) conditions. Both
      the rate of non-cyclic electron flow and the rate of electron flow to CO(2) or
      O(2) increased with increasing leaf N at any given C(i). The percentage of non
      cyclic electron flow to CO(2) assimilation, however, remained the same regardless
      of leaf N content. As C(i) increased, the percentage of non-cyclic electron flow
      to CO(2) assimilation increased. In conclusion, the relationship between PSII
      quantum efficiency and quantum yield for CO(2) assimilation and the partitioning
      of electron flow between CO(2) assimilation and photorespiration are not affected
      by N content in apple leaves.

PMID- 11520876
TI  - Direct measurement of sodium and potassium in the transpiration stream of salt
      excluding and non-excluding varieties of wheat.
AB  - The xylem-feeding insect Philaenus spumarius was used to analyse sodium and
      potassium fluxes in the xylem of intact, transpiring wheat plants. Two cultivars
      were compared: the salt-excluding (Chinese Spring) and the non-excluding
      (Langdon). Chinese Spring accumulated much less sodium in its leaves than the
      salt-sensitive Langdon. After 7 d in 150 mol m(-3) NaCl, the sodium concentration
      in the leaf sap of Langdon reached over 600 mol m(-3). This was some three-fold
      greater than that in Chinese Spring. Similar findings have previously been
      reported from these cultivars. The reduced ion accumulation was specific to
      sodium; accumulation of K(+) was unaffected by NaCl in Chinese Spring, such that
      it developed a much lower leaf Na(+)/K(+) ratio than Langdon. The spittlebug, P.
      spumarius was used to sample xylem sap from both cultivars. This approach showed
      that the leaf xylem sap of Chinese Spring had much lower levels of sodium than
      that of Langdon. In the 150 mol m(-3) NaCl treatment, sodium levels in the leaf
      xylem reached only 2-3 mol m(-3) in Chinese Spring, compared with 8-10 mol m(-3)
      in Langdon. Transpiration rates were found to be similar in the two varieties.
      The lower leaf xylem content alone was thus sufficient to account for the reduced
      accumulation of sodium in leaves of Chinese Spring. The mechanisms by which xylem
      sodium might be lowered are discussed and it is concluded that sodium is probably
      excluded from the xylem in the root of Chinese Spring.

PMID- 11520877
TI  - Arbuscular mycorrhizal fungi alter phosphorus relations of broomsedge (Andropogon
      virginicus L.) plants.
AB  - Broomsedge (Andropogon virginicus L.) is a dominant grass revegetating many
      abandoned coal-mined lands in West Virginia, USA. Residual soils on such sites
      are often characterized by low pH, low nutrients, and high aluminium. Experiments
      were conducted to assess the resistance of broomsedge to limited phosphorus (Pi)
      availability and to investigate the role that arbuscular mycorrhizal (AM) fungi
      play in aiding plant growth under low Pi conditions. Pregerminated mycorrhizal
      and non-mycorrhizal seedlings were grown in a sand-culture system with nutrient
      solutions containing Pi concentrations ranging from 10 to 100 microM for 8 weeks.
      Non-mycorrhizal plants exhibited severe inhibition of growth under Pi limitation
      (<60 microM). Colonization by AM fungi (combined Glomus clarum Nicolson & Schenck
      and Gigaspora gigantea (Nicol. & Gerd.) Gerd. & Trappe) greatly enhanced host
      plant growth at low Pi concentrations, but did not benefit growth when Pi was
      readily available (100 microM). In comparison to non-mycorrhizal plants,
      mycorrhizal plants had higher phosphorus use efficiency at low Pi concentrations
      and maintained nearly constant tissue nutrient concentrations across the gradient
      of Pi concentrations investigated. Manganese (Mn) and sodium (Na) accumulated in
      shoots of non-mycorrhizal plants under Pi limitation. Mycorrhizal plants
      exhibited lower instantaneous Pi uptake rates and significantly lower C(min)
      values compared to non-mycorrhizal plants. These patterns suggest that the
      symbiotic association between broomsedge roots and AM fungi effectively maintains
      nutrient homeostasis through changes in physiological properties, including
      nutrient uptake, allocation and use. The mycorrhizal association is thus a major
      adaptation that allows broomsedge to become established on infertile mined lands.

PMID- 11520878
TI  - Effect of temperature on cuticular transpiration of isolated cuticular membranes
      and leaf discs.
AB  - Cuticular transpiration was measured in the temperature range between 10 degrees
      C and 55 degrees C using tritiated water and five species (Vinca major L., Prunus
      laurocerasus L., Forsythia intermedia L., Citrus aurantium L., and Hedera helix
      L.). Cuticular water permeabilities measured with isolated cuticular membranes
      were not different from cuticular water permeabilities measured with leaf discs.
      Depending on the species cuticular water permeabilities increased by factors
      between 12 (V. major) to 264 (H. helix) when temperature was increased from 10
      degrees C to 55 degrees C. Arrhenius plots (lnP versus 1/T) of all investigated
      species were characterized by phase transitions occurring in the temperature
      range of 30-39 degrees C. Activation energies for water permeability across plant
      cuticles below and above the midpoint of phase transition were calculated from
      Arrhenius plots. Depending on the species they varied between 26 (F. intermedia)
      to 61 kJ mol(-1) (H. helix) below the phase transition and from 67 (V. major) to
      122 kJ mol(-1) (F. intermedia) above the phase transition. Since the occurrence
      of phase transitions always lead to significantly increased rates of cuticular
      transpiration it is argued that temperatures higher than 35 degrees C caused
      structural defects to the transport-limiting barrier of the plant cuticles of all
      species investigated.

PMID- 11520879
TI  - Does nitrogen supply affect the response of wheat (Triticum aestivum cv. Hanno)
      to the combination of elevated CO(2) and O(3)?
AB  - Spring wheat (Triticum aestivum cv. Hanno) was grown at ambient (350 micromol
      mol(-1)) or elevated CO(2) (700 micromol mol(-1)) in charcoal/Purafil-filtered
      air (CFA <5 nmol mol(-1)) or ozone (CFA +75 nmol mol(-1) 7 h d(-1)) at three
      levels of N supply (1.5, 4 and 14 mM NO(-3)), to test the hypothesis that the
      combined impacts of elevated CO(2) and O(3) on plant growth and photosynthetic
      capacity are affected by nitrogen availability. Shifts in foliar N content
      reflected the level of N supplied, and the growth stimulation induced by elevated
      CO(2) was dependent on the level of N supply. At 60 d after transfer (DAT),
      elevated CO(2) was found to increase total biomass by 44%, 29%, 12% in plants
      supplied with 14, 4 and 1.5 mM NO(-3), respectively, and there was no evidence of
      photosynthetic acclimation to elevated CO(2) across N treatments; the maximum in
      vivo rate of Rubisco carboxylation (V(cmax)) was similar in plants raised at
      elevated and ambient CO(2). At 60 DAT, ozone exposure was found to suppress plant
      relative growth rate (RGR) and net photosynthesis (A) in plants supplied with 14
      and 4 mM NO(-3). However, O(3) had no effect on the RGR of plants supplied with
      1.5 mM NO(-3) and this effect was accompanied by a reduced impact of the
      pollutant on A. Elevated CO(2) counteracted the detrimental effects of O(3) (i.e.
      the same ozone concentration that depressed RGR and A at ambient CO(2) resulted
      in no significant effects when plants were raised at elevated CO(2)) at all
      levels of N supply and the effect was associated with a decline in O(3) uptake at
      the leaf level.

PMID- 11520880
TI  - Interactive effects of soil temperature, atmospheric carbon dioxide and soil N on
      root development, biomass and nutrient uptake of winter wheat during vegetative
      growth.
AB  - Nutrient requirements for plant growth are expected to rise in response to the
      predicted changes in CO(2) and temperature. In this context, little attention has
      been paid to the effects of soil temperature, which limits plant growth at early
      stages in temperate regions. A factorial growth-room experiment was conducted
      with winter wheat, varying soil temperature (10 degrees C and 15 degrees C),
      atmospheric CO(2) concentration (360 and 700 ppm), and N supply (low and high).
      The hypothesis was that soil temperature would modify root development, biomass
      allocation and nutrient uptake during vegetative growth and that its effects
      would interact with atmospheric CO(2) and N availability. Soil temperature
      effects were confirmed for most of the variables measured and 3-factor
      interactions were observed for root development, plant biomass components, N-use
      efficiency, and shoot P content. Importantly, the soil temperature effects were
      manifest in the absence of any change in air temperature. Changes in root
      development, nutrient uptake and nutrient-use efficiencies were interpreted as
      counterbalancing mechanisms for meeting nutrient requirements for plant growth in
      each situation. Most variables responded to an increase in resource availability
      in the order: N supply >soil temperature >CO(2).

PMID- 11520881
TI  - High-resolution analysis of tomato leaf elongation: the application of novel time
      series analysis techniques.
AB  - This paper demonstrates the use of a novel suite of data-based, recursive
      modelling techniques for the investigation of biological and other time-series
      data, including high resolution leaf elongation. The Data-Based Mechanistic (DBM)
      modelling methodology rejects the common practice of empirical curve fitting for
      a more objective approach where the model structure is not assumed a priori, but
      instead is identified directly from the data series in a stochastic form.
      Further, this novel approach takes advantage of the latest techniques in optimal
      recursive estimation of non-stationary and non-linear time-series. Here, the
      utility and ease of use of these techniques is demonstrated in the examination of
      two time-series of leaf elongation in an expanding leaf of tomato (Lycopersicon
      esculentum L. cv. Ailsa Craig) growing in a root pressure vessel (RPV). Using
      this analysis, the component signals of the elongation series are extracted and
      considered in relation to physiological processes. It is hoped that this paper
      will encourage the wider use of these new techniques, as well as the associated
      Data-Based Mechanistic (DBM) modelling strategy, in analytical plant physiology.

PMID- 11520882
TI  - Discontinuous single electrode voltage-clamp measurements: assessment of clamp
      accuracy in Vicia faba guard cells.
AB  - The use of a discontinuous single electrode voltage-clamp (dSEVC) offers an
      attractive alternative to the patch-clamp technique, since whole-cell
      measurements can be performed with a single sharp electrode. Comparison of
      current-voltage relations, however, revealed a weaker voltage dependence of
      channels measured with the dSEVC compared to patch clamp. The accuracy of the
      dSEVC was tested on Vicia faba guard cells impaled with double-barrelled
      electrodes. The actual clamp potential was measured independently of the dSEVC,
      at the second barrel. The weaker voltage dependence of ion channels appeared to
      be due to an overestimation of the clamp potential by the dSEVC. The deviation
      between the intended and actual clamp potential showed a linear relationship with
      the injected current; on average a 126 mV deviation was found for a clamp current
      of 1 nA. The deviation was probably caused by a slow settling capacity at the
      electrode, not compensated by the dSEVC amplifier. It is concluded that the dSEVC
      method in its current state is only suited for the study of small ion
      conductances in plant cells.

PMID- 11520883
TI  - A fruit-specific and developmentally regulated endopolygalacturonase gene from
      strawberry (Fragaria x ananassa cv. Chandler).
AB  - A fruit-specific and developmentally regulated polygalacturonase gene (spG gene)
      from strawberry (Fragaria x ananassa cv. Chandler) has been cloned and
      characterized at a molecular and physiological level. Comparison analysis of the
      corresponding deduced sPG protein have shown that this strawberry gene is similar
      to Clade A endopolygalacturonase genes. Moreover, the spatio-temporal and
      hormonal gene expression pattern suggests a close relationship between the
      expression of this gene and the onset of the strawberry fruit ripening process
      and agrees with that of the production of oligosaccharins which have already been
      described as active molecules involved in fruit ripening. The results are
      discussed in terms of a putative role of this enzyme in the release of
      oligosaccharins from the strawberry fruit cell wall.

PMID- 11520884
TI  - Cryptogein affects expression of alpha3, alpha6 and beta1 20S proteasome subunits
      encoding genes in tobacco.
AB  - Twelve alpha and beta 20S proteasome subunits cDNAs showing 70-82% identity with
      the corresponding genes in Arabidopsis or rice, and features of eukaryotic
      proteasome subunits were cloned in tobacco. Only beta1-tcI 7, alpha3 and alpha6,
      20S proteasome subunits encoding genes were up-regulated by cryptogein, a
      proteinaceous elicitor of plant defence reactions. These results led to the
      hypothesis that the activation of beta1-tcI 7, alpha3 and alpha6 could induce a
      specific proteolysis involved in the hypersensitive response and systemic
      acquired resistance monitored by cryptogein.

PMID- 11520885
TI  - Eight cDNA encoding putative aquaporins in Vitis hybrid Richter-110 and their
      differential expression.
AB  - The nucleotide sequences of eight cDNAs encoding putative aquaporins obtained
      from a leaf Vitis hybrid Richter-110 cDNA library are reported. They encode
      proteins ranging from 249 to 287 amino acids with characteristic sequences that
      clearly include them within the MIP family. According to available database
      sequence homologies, they can be classified into four groups belonging to two
      subfamilies: PIP (PIP1 and PIP2) and TIP (gamma-TIP and delta-TIP). In order to
      elucidate the expression patterns of these putative aquaporins in the plant,
      specific probes were developed and tissue specific differential expression was
      tested by reverse Northern and compared with two reference genes (malic enzyme
      and glutamate dehydrogenase). Clearly, most of the putative aquaporins had higher
      expression in roots, whereas expression in shoot and leaves was generally weaker
      than the reference genes.

PMID- 11520887
TI  - Presynaptic autoreceptors.

PMID- 11520888
TI  - Autoreceptors do not regulate routinely neurotransmitter release: focus on
      adrenergic systems.
AB  - The theory that neurotransmitter release is regulated locally at the individual
      terminals of neurons has achieved a rapid and seemingly secure status in our
      understanding of neuronal function both in the periphery and in the central
      nervous system. This concept of negative feedback control through the monitoring
      of the perineuronal concentration of previously released transmitter has been
      extended to a multiplicity of transmitters and utilized to explain the mechanisms
      of action of diverse classes of drugs, ranging from antihypertensives to
      antidepressants. It is my view that negative feedback by terminal and by
      somadendritic receptors cannot account for the existing body of experimental
      work. Analyses of the profiles of action of agonists and antagonists, and of the
      per pulse release of transmitter in the absence of drugs in a variety if
      peripheral organ systems, as well as in superfused brain slices, demonstrates the
      need for alternate interpretations of the available data. Evidence is provided
      that the actions of agonists to inhibit transmitter release and that of
      antagonists to enhance release occur at different cellular loci and that the
      purported unitary action of these two classes that is so central to the validity
      of presynaptic theory is unsupportable.

PMID- 11520889
TI  - Presynaptic autoreceptors in the third decade: focus on alpha2-adrenoceptors.

PMID- 11520890
TI  - Partial resistance to malonate-induced striatal cell death in transgenic mouse
      models of Huntington's disease is dependent on age and CAG repeat length.
AB  - Transgenic Huntington's disease (HD) mice, expressing exon 1 of the HD gene with
      an expanded CAG repeat, are totally resistant to striatal lesion induced by
      excessive NMDA receptor activation. We now show that striatal lesions induced by
      the mitochondrial toxin malonate are reduced by 70-80% in transgenic HD mice
      compared with wild-type littermate controls. This occurred in 6- and 12-week-old
      HD mice with 150 CAG repeats (line R6/2) and in 18-week-old, but not 6-week-old,
      HD mice with 115 CAG repeats (line R6/1). Therefore, we show for the first time
      that the resistance to neurotoxin in transgenic HD mice is dependent on both the
      CAG repeat length and the age of the mice. Importantly, most HD patients develop
      symptoms in adulthood and exhibit an inverse relationship between CAG repeat
      length and age of onset. Transgenic mice expressing a normal CAG repeat (18 CAG)
      were not resistant to malonate. Although endogenous glutamate release has been
      implicated in malonate-induced cell death, glutamate release from striatal
      synaptosomes was not decreased in HD mice. Malonate-induced striatal cell death
      was reduced by 50-60% in wild-type mice when they were treated with either the
      NMDA receptor antagonist MK-801 or the caspase inhibitor zVAD-fmk. These two
      compounds did not reduce lesion size in transgenic R6/1 mice. This might suggest
      that NMDA receptor- and caspase-mediated cell death pathways are inhibited and
      that the limited malonate-induced cell death still occurring in HD mice is
      independent of these pathways. There were no changes in striatal levels of the
      two anti cell death proteins Bcl-X(L) and X-linked inhibitor of apoptosis protein
      (XIAP), before or after the lesion in transgenic HD mice. We propose that mutant
      huntingtin causes a sublethal grade of metabolic stress which is CAG repeat
      length-dependent and results in up-regulation over time of cellular defense
      mechanisms against impaired energy metabolism and excitotoxicity.

PMID- 11520891
TI  - Pentyl-4-yn-valproic acid enhances both spatial and avoidance learning, and
      attenuates age-related NCAM-mediated neuroplastic decline within the rat medial
      temporal lobe.
AB  - 2-N-Pentyl-4-pentynoic acid [pentyl-4-yn-valproic acid (VPA)] is an analogue of
      valproic acid that induces neuritogenesis and increases neural cell adhesion
      molecule (NCAM) prevalence in cultured neural cells. As memory consolidation
      involves synapse growth, aided by cell adhesion molecule function, we determined
      whether or not pentyl-4-yn-VPA had cognition-enhancing properties. Pentyl-4-yn
      VPA (16-85 mg/kg) significantly improved water maze learning and task retention
      when given prior to each training session. Acute administration of pentyl-4-yn
      VPA also influenced memory consolidation processes as, when given at 3 h post
      passive avoidance training, the amnesia induced by scopolamine given 6 h post
      training was prevented in a dose-dependent manner. Chronic administration of
      pentyl-4-yn-VPA (16.8 or 50.4 mg/kg) also significantly reduced escape latencies
      in the water maze task, 24 h following the last drug administration. This
      improved spatial learning was accompanied by enhanced neuroplasticity as the
      expression of NCAM polysialylated neurons in the infragranular zone of the
      dentate gyrus and in layer II of the perirhinal and piriform cortex was increased
      significantly following chronic drug treatment. The cognition-enhancing qualities
      of pentyl-4-yn-VPA, combined with its ability to attenuate the age-related loss
      of the NCAM polysialylation state, suggest that it may effectively slow the onset
      of cognitive decline.

PMID- 11520892
TI  - Modulation of NMDA-mediated excitotoxicity by protein kinase C.
AB  - Excessive activation of N-methyl-D-aspartate (NMDA) receptors leads to cell death
      in human embryonic kidney-293 (HEK) cells which have been transfected with
      recombinant NMDA receptors. To evaluate the role of protein kinase C (PKC)
      activation in NMDA-mediated toxicity, we have analyzed the survival of
      transfected HEK cells using trypan blue exclusion. We found that NMDA-mediated
      death of HEK cells transfected with NR1/NR2A subunits was increased by exposure
      to phorbol esters and reduced by inhibitors of PKC activation, or PKC down
      regulation. The region of NR2A that provides the PKC-induced enhancement of cell
      death was localized to a discrete segment of the C-terminus. Use of isoform
      specific PKC inhibitors showed that Ca(2+)- and lipid-dependent PKC isoforms
      (cPKCs), specifically PKCbeta1, was responsible for the increase in cell death
      when phorbol esters were applied prior to NMDA in these cells. PKC activity
      measured by an in vitro kinase assay was also increased in NR1A/NR2A-transfected
      HEK cells following NMDA stimulation. These results suggest that PKC acts on the
      C-terminus of NR2A to accentuate cell death in NR1/NR2A-transfected cells and
      demonstrate that this effect is mediated by cPKC isoforms. These data indicate
      that elevation of cellular PKC activity can increase neurotoxicity mediated by
      NMDA receptor activation.

PMID- 11520893
TI  - Transfection-enforced Bcl-2 overexpression and an anti-Parkinson drug,
      rasagiline, prevent nuclear accumulation of glyceraldehyde-3-phosphate
      dehydrogenase induced by an endogenous dopaminergic neurotoxin, N
      methyl(R)salsolinol.
AB  - An endogenous dopaminergic neurotoxin, N-methyl(R)salsolinol, was found to induce
      apoptosis in human dopaminergic SH-SY5Y cells by step-wise activation of
      apoptotic cascade; collapse in mitochondrial membrane potential, DeltaPsim,
      activation of caspases, and fragmentation of DNA. Recently, accumulation of
      gylceraldehyde-3-phosphate dehydrogenase (GAPDH) in nuclei was proposed to play
      an important role in apoptosis. In this paper, involvement of GAPDH in apoptosis
      induced by N-methyl(R)salsolinol was studied. The isoquinoline reduced DeltaPsim
      within 3 h, as detected by a fluorescence indicator, JC-1, then after 16 h
      incubation, GAPDH accumulated in nuclei by detection with immunostaining. To
      clarify the role of GAPDH in apoptotic process, a stable cell line of Bcl-2
      overexpressed SH-SY5Y cells was established. Overexpression of Bcl-2 prevented
      the decline in DeltaPsim and also apoptotic DNA damage induced by N
      methyl(R)salsolinol. In Bcl-2 transfected cells, nuclear translocation of GAPDH
      was also completely suppressed. In addition, a novel antiparkinsonian drug,
      rasagiline, prevented nuclear accumulation of GAPDH induced by N
      methyl(R)salsolinol in control cells. These results suggest that GAPDH may
      accumulate in nuclei as a consequence of signal transduction, which is
      antagonized by anti-apoptotic Bcl-2 protein family and rasagiline. The results
      are discussed in concern to intracellular mechanism underlying anti-apoptotic
      function of rasagiline analogues.

PMID- 11520894
TI  - Intraneuronal N-acetylaspartate supplies acetyl groups for myelin lipid
      synthesis: evidence for myelin-associated aspartoacylase.
AB  - Despite its growing use as a radiological indicator of neuronal viability, the
      biological function of N-acetylaspartate (NAA) has remained elusive. This is due
      in part to its unusual metabolic compartmentalization wherein the synthetic
      enzyme occurs in neuronal mitochondria whereas the principal metabolizing enzyme,
      N-acetyl-L-aspartate amidohydrolase (aspartoacylase), is located primarily in
      white matter elements. This study demonstrates that within white matter,
      aspartoacylase is an integral component of the myelin sheath where it is ideally
      situated to produce acetyl groups for synthesis of myelin lipids. That it
      functions in this manner is suggested by the fact that myelin lipids of the rat
      optic system are well labeled following intraocular injection of [14C-acetyl]NAA.
      This is attributed to uptake of radiolabeled NAA by retinal ganglion cells
      followed by axonal transport and transaxonal transfer of NAA into myelin, a
      membrane previously shown to contain many lipid synthesizing enzymes. This study
      identifies a group of myelin lipids that are so labeled by neuronal [14C]NAA, and
      demonstrates a different labeling pattern from that produced by neuronal
      [14C]acetate. High performance liquid chromatographic analysis of the
      deproteinated soluble materials from the optic system following intraocular
      injection of [14C]NAA revealed only the latter substance and no radiolabeled
      acetate, suggesting little or no hydrolysis of NAA within mature neurons of the
      optic system. These results suggest a rationale for the unusual
      compartmentalization of NAA metabolism and point to NAA as a neuronal constituent
      that is essential for the formation and/or maintenance of myelin. The relevance
      of these findings to Canavan disease is discussed.

PMID- 11520895
TI  - Dependence of excitotoxic neurodegeneration on mitochondrial aconitase
      inactivation.
AB  - Using the inactivation of mitochondrial and cytosolic aconitases as markers of
      compartment-specific superoxide (O2(-)) production, we show that oxygen-glucose
      deprivation (OGD) or excitotoxin exposure produce a time-dependent inactivation
      of mitochondrial, but not cytosolic, aconitase in cortical cultures. To determine
      if mitochondrial O2(-) production was an important determinant in neuronal death
      resulting from OGD, metalloporphyrins with varying superoxide dismutase (SOD)
      activity were tested for their ability to protect against mitochondrial aconitase
      inactivation and cell death. OGD-induced mitochondrial aconitase inactivation and
      cell death was inhibited by manganese tetrakis (4-benzoic acid) porphyrin
      (MnTBAP), manganese tetrakis (N-ethylpyridinium-2-yl) porphyrin (MnTE-2-PyP) and
      NMDA receptor antagonists. By contrast, NMDA- or kainate (KA)-induced
      mitochondrial aconitase inactivation and cell death was inhibited by MnTBAP, but
      not MnTE-2-PyP. Moreover, both MnTBAP and MnTE-2-PyP penetrated mitochondrial
      fractions of cortical cells. These data suggest that mitochondrial aconitase
      inactivation closely correlates with subsequent neuronal death following
      excitotoxicity produced by OGD or NMDA/KA exposure. Assessment of biological
      rather biochemical antioxidant activities better predicted neuroprotection by
      metalloporphyrins. Moreover, antioxidants that protect oxidant-sensitive
      mitochondrial targets such as aconitase may be useful as therapies for disease
      states involving excitotoxicity.

PMID- 11520896
TI  - Cyclic AMP-dependent protein kinase phosphorylates group III metabotropic
      glutamate receptors and inhibits their function as presynaptic receptors.
AB  - Recent evidence suggests that the functions of presynaptic metabotropic glutamate
      receptors (mGluRs) are tightly regulated by protein kinases. We previously
      reported that cAMP-dependent protein kinase (PKA) directly phosphorylates mGluR2
      at a single serine residue (Ser843) on the C-terminal tail region of the
      receptor, and that phosphorylation of this site inhibits coupling of mGluR2 to
      GTP-binding proteins. This may be the mechanism by which the adenylyl cyclase
      activator forskolin inhibits presynaptic mGluR2 function at the medial perforant
      path-dentate gyrus synapse. We now report that PKA also directly phosphorylates
      several group III mGluRs (mGluR4a, mGluR7a, and mGluR8a), as well as mGluR3 at
      single conserved serine residues on their C-terminal tails. Furthermore,
      activation of PKA by forskolin inhibits group III mGluR-mediated responses at
      glutamatergic synapses in the hippocampus. Interestingly, beta-adrenergic
      receptor activation was found to mimic the inhibitory effect of forskolin on both
      group II and III mGluRs. These data suggest that a common PKA-dependent mechanism
      may be involved in regulating the function of multiple presynaptic group II and
      group III mGluRs. Such regulation is not limited to the pharmacological
      activation of adenylyl cyclase but can also be elicited by the stimulation of
      endogenous G(s)-coupled receptors, such as beta-adrenergic receptors.

PMID- 11520897
TI  - Soluble forms of NCAM and F3 neuronal cell adhesion molecules promote Schwann
      cell migration: identification of protein tyrosine phosphatases zeta/beta as the
      putative F3 receptors on Schwann cells.
AB  - Neural cell adhesion molecule (NCAM) and F3 are both axonal adhesion molecules
      which display homophilic (NCAM) or heterophilic (NCAM, F3) binding activities and
      participate in bidirectional exchange of information between neurones and glial
      cells. Engineered Fc chimeric molecules are fusion proteins that contain the
      extracellular part of NCAM or F3 and the Fc region of human IgG1. Here, we
      investigated the effect of NCAM-Fc and F3-Fc chimeras on Schwann cell (SC)
      migration. Binding sites were identified at the surface of cultured SCs by
      chimera coated fluorospheres. The functional effect of NCAM-Fc and F3-Fc binding
      was studied in two different SC migration models. In the first, migration is
      monitored at specific time intervals inside a 1-mm gap produced in a monolayer
      culture of SCs. In the second, SCs from a dorsal root ganglion explant migrate on
      a sciatic nerve cryosection. In both systems addition of the chimeras
      significantly increased the extent of SC migration and this effect could be
      prevented by the corresponding anti-NCAM or anti-F3 blocking antibodies.
      Furthermore, antiproteoglycan-type protein tyrosine phosphatase zeta/beta
      (RPTPzeta/beta) antibodies identified the presence of RPTPzeta/beta on SCs and
      prevented the enhancing effect of soluble F3 on SC motility by 95%. The F3-Fc
      coated Sepharose beads precipitated RPTPzeta/beta from SC lysates. Altogether
      these data point to RPTPzeta/beta is the putative F3 receptor on SCs. These
      results identify F3 and NCAM receptors on SC as potential mediators of signalling
      occurring between axons and glial cells during peripheral nerve development and
      regeneration.

PMID- 11520898
TI  - Changes in the phosphorylation of initiation factor eIF-2alpha, elongation factor
      eEF-2 and p70 S6 kinase after transient focal cerebral ischaemia in mice.
AB  - Mice were subjected to 60 min occlusion of the left middle cerebral artery (MCA)
      followed by 1-6 h of reperfusion. Tissue samples were taken from the MCA
      territory of both hemispheres to analyse ischaemia-induced changes in the
      phosphorylation of the initiation factor eIF-2alpha, the elongation factor eEF-2
      and p70 S6 kinase by western blot analysis. Tissue sections from additional
      animals were taken to evaluate ischaemia-induced changes in global protein
      synthesis by autoradiography and changes in eIF-2alpha phosphorylation by
      immunohistochemistry. Transient MCA occlusion induced a persistent suppression of
      protein synthesis. Phosphorylation of eIF-2alpha was slightly increased during
      ischaemia, it was markedly up-regulated after 1 h of reperfusion and it
      normalized after 6 h of recirculation despite ongoing suppression of protein
      synthesis. Similar changes in eIF-2alpha phosphorylation were induced in primary
      neuronal cell cultures by blocking of endoplasmic reticulum (ER) calcium pump,
      suggesting that disturbances of ER calcium homeostasis may play a role in
      ischaemia-induced changes in eIF-2alpha phosphorylation. Dephosphorylation of eIF
      2alpha was not paralleled by a rise in levels of p67, a glycoprotein that
      protects eIF-2alpha from phosphorylation, even in the presence of active eIF
      2alpha kinase. Phosphorylation of eEF-2 rose moderately during ischaemia, but
      returned to control levels after 1 h of reperfusion and declined markedly below
      control levels after 3 and 6 h of recirculation. In contrast to the only short
      lasting phosphorylation of eIF-2a and eEF-2, transient focal ischaemia induced a
      long-lasting dephosphorylation of p70 S6 kinase. The results suggest that
      blocking of elongation does not play a major role in suppression of protein
      synthesis induced by transient focal cerebral ischaemia. Investigating the
      factors involved in ischaemia-induced suppression of the initiation step of
      protein synthesis and identifying the underlying mechanisms may help to further
      elucidate those disturbances directly related to the pathological process
      triggered by transient cerebral ischaemia and leading to neuronal cell injury.

PMID- 11520899
TI  - Relationship between dopamine-stimulated phospholipid methylation and the single
      carbon folate pathway.
AB  - In a previous study we demonstrated the ability of dopamine (DA) to stimulate
      phospholipid methylation (PLM) via a novel mechanism involving the D4 dopamine
      receptor (D4R) in which single-carbon folates appeared to be the primary source
      of methyl groups. To further understand the relationship between D4R-mediated PLM
      and folate metabolism, we examined the effect of several folate pathway
      interventions on the level of basal and DA-stimulated incorporation of [14C]
      labeled formate into phospholipids in cultured SH-SY5Y neuroblastoma cells. These
      interventions included: (i) Overexpression of methenyltetrahydrofolate synthetase
      (MTHFS). (ii) Treatment with 5-formylTHF. (iii) Treatment with the MTHFS
      inhibitor 5-formyltetrahydrohomofolic acid (5-formylTHHF). (iv) Growth in
      nucleoside-free media. 31P-NMR was also used to follow DA-induced changes in cell
      phospholipid composition. MTHFS overexpression and 5-formylTHHF treatment, both
      of which lower 5-methylTHF levels, each reduced basal PLM and its stimulation by
      DA. In contrast, 5-formylTHF, which increases 5-methylTHF, caused a dose
      dependent increase in both basal and DA-stimulated PLM. Growth in nucleoside-free
      media caused time-dependent changes in PLM, which were due to the absence of
      purine nucleosides. While basal PLM was maintained at a reduced level, DA
      stimulated PLM was initially increased followed by a later decrease. Together,
      these findings indicate a close functional relationship between single-carbon
      folate metabolism and DA-stimulated PLM, consistent with a role for 5-methylTHF
      as the methyl donor for the D4R-mediated process.

PMID- 11520900
TI  - Differential capacities of the RGS1, RGS16 and RGS-GAIP regulators of G protein
      signaling to enhance alpha2A-adrenoreceptor agonist-stimulated GTPase activity of
      G(o1)alpha.
AB  - Recombinant RGS1, RGS16 and RGS-GAIP, but not RGS2, were able to substantially
      further stimulate the maximal GTPase activity of G(o1)alpha promoted by agonists
      at the alpha2A-adrenoreceptor in a concentration-dependent manner. Kinetic
      analysis of the regulation of an alpha2A-adrenoreceptor-G(o1)alpha fusion protein
      by all three RGS proteins revealed that they had similar affinities for the
      receptor-G protein fusion. However, their maximal effects on GTP hydrolysis
      varied over threefold with RGS16 > RGS1 > RGS-GAIP. Both RGS1 and RGS16 reduced
      the potency of the alpha2A-adrenoreceptor agonist adrenaline by some 10-fold. A
      lower potency shift was observed for the partial agonist UK14304 and the effect
      was absent for the weak partial agonist oxymetazoline. Each of these RGS proteins
      altered the intrinsic activity of both UK14304 and oxymetazoline relative to
      adrenaline. Such results require the RGS interaction with G(o1)alpha to alter the
      conformation of the alpha2A-adrenoreceptor and are thus consistent with models
      invoking direct interactions between RGS proteins and receptors. These studies
      demonstrate that RGS1, RGS16 and RGS-GAIP show a high degree of selectivity to
      regulate alpha2A-adrenoreceptor-activated G(o1)alpha rather than G(i1)alpha,
      G(i2)alpha or G(i3)alpha and different capacities to inactivate this G protein.

PMID- 11520901
TI  - Deficiency of presenilin-1 increases calcium-dependent vulnerability of neurons
      to oxidative stress in vitro.
AB  - We examined the function of presenilin-1 (PS1) on neuronal resistance to
      oxidative stress. CNS neurons cultured from PS1-deficient mice exhibited
      increased vulnerability to H2O2 treatment compared with those from wild-type
      mice. Antioxidants protected the cultured neurons against the oxidative stress.
      An intracellular calcium chelator, BAPTA AM, as well as an L-type voltage
      dependent calcium channel blocker, nifedipine, rescued the neurons from H2O2
      induced death, while an N-type voltage-dependent calcium channel blocker, omega
      conotoxin, or calcium release blockers from ER stores, dantrolene and
      xestospongin C, failed to rescue them. Wild-type and PS1-deficient neurons showed
      comparable increases of cytoplasmic free calcium levels after exposure to H2O2.
      Taken together with the data that PS1-deficient neurons exhibited increased
      vulnerability to glutamate, these findings imply that PS1 confers resistance to
      oxidative stress on neurons in calcium-dependent manners.

PMID- 11520902
TI  - High-affinity sodium-vitamin C co-transporters (SVCT) expression in embryonic
      mouse neurons.
AB  - The sodium-vitamin C co-transporters SVCT1 and SVCT2 transport the reduced form
      of vitamin C, ascorbic acid. High expression of the SVCT2 has been demonstrated
      in adult neurons and choroid plexus cells by in situ hybridization. Additionally,
      embryonic mesencephalic dopaminergic neurons express the SVCT2 transporter.
      However, there have not been molecular and kinetic analyses addressing the
      expression of SVCTs in cortical embryonic neurons. In this work, we confirmed the
      expression of a SVCT2-like transporter in different regions of the fetal mouse
      brain and in primary cultures of neurons by RT-PCR. Kinetic analysis of the
      ascorbic acid uptake demonstrated the presence of two affinity constants, 103
      microM and 8 microM. A K(m) of 103 microM corresponds to a similar affinity
      constant reported for SVCT2, while the K(m) of 8 microM might suggest the
      expression of a very high affinity transporter for ascorbic acid. Our uptake
      analyses also suggest that neurons take up dehydroascorbic acid, the oxidized
      form of vitamin C, through the glucose transporters. We consider that the early
      expression of SVCTs transporters in neurons is important in the uptake of vitamin
      C, an essential molecule for the fetal brain physiology. Vitamin C that is found
      at high concentration in fetal brain may function in preventing oxidative free
      radical damage, because antioxidant radical enzymes mature only late in the
      developing brain.

PMID- 11520903
TI  - Dystroglycan contributes to the formation of multiple dystrophin-like complexes
      in brain.
AB  - In muscle, dystrophin anchors a complex of proteins at the cell surface which
      includes alpha-dystroglycan, beta-dystroglycan, syntrophins and dystrobrevins.
      Mutations in the dystrophin gene lead to muscular dystrophy and mental
      retardation. In contrast to muscle, little is known about the localization and
      the molecular interactions of dystrophin and dystrophin associated proteins
      (DAPs) in brain. In the present study, we show that alpha-dystroglycan and
      dystrophin are localized to large neurones in cerebral cortex, hippocampus,
      cerebellum and spinal cord. Furthermore, we show that dystroglycan is a member of
      three distinct dystrophin-containing complexes. Two of these complexes contain
      syntrophin and both dystrophin and syntrophin are enriched in post-synaptic
      densities. These data suggest that dystrophin and DAPs may have a role in the
      organization of CNS synapses. Interestingly, the enrichment for syntrophin in
      post-synaptic densities is not affected in mice mutant for all dystrophin
      isoforms. Thus in the brain, unlike in muscle, the association of syntrophin with
      dystrophin is not crucial for the DAP complex which suggests that it may be
      associated with other proteins.

PMID- 11520904
TI  - Selective cannabinoid CB1 receptor-mediated inhibition of inducible nitric oxide
      synthase protein expression in C6 rat glioma cells.
AB  - We have studied the effects of two cannabinoid receptor agonists, WIN 55,212-2
      and cannabinol, on nitric oxide (NO) production and inducible nitric oxide
      synthase (iNOS) expression in the C6 glioma cell line. After 24 h of
      lipopolysaccharide (LPS) (1 microg/mL) and interferon-gamma (IFN-gamma) (300
      U/mL) stimulation, a significant increase in NO production, evaluated as nitrite,
      was observed in the culture medium. WIN 55,212-2 (0.1-10000 nM) and cannabinol
      (0.3-30000 nM), dose-dependently inhibited nitrite production showing a different
      potency (WIN 55,212-2 EC(50): 4.2 nM; cannabinol EC(50): 700 nM). WIN 55,212-2
      (100 nM), given concomitantly to the stimulus also inhibited iNOS expression but
      had no effect when added to the cells 2 h after LPS/IFN-gamma, indicating a
      possible interference at the protein synthesis level or at an earlier step, as
      gene transcription. The cannabinoid CB1 receptor antagonist, SR141716A (0.1-100
      nM), but not the cannabinoid CB2 receptor antagonist, SR144528 (0.1-100 nM),
      reduced in a dose-related manner WIN 55,212-2-and cannabinol-induced inhibition
      of nitrite production. SR141161A also reversed the WIN 55,212-2-induced
      inhibition of iNOS expression. These data suggest that selective cannabinoid CB1
      receptor activation, by inhibiting iNOS expression and NO overproduction in glial
      cells, might be helpful in NO-mediated inflammation leading to neurodegeneration.

PMID- 11520905
TI  - Kynurenine pathway metabolism in human astrocytes: a paradox for neuronal
      protection.
AB  - There is good evidence that the kynurenine pathway (KP) and one of its products,
      quinolinic acid (QUIN), play a role in the pathogenesis of neurological diseases,
      in particular AIDS dementia complex. Although QUIN has been shown to be produced
      in neurotoxic concentrations by macrophages and microglia, the role of astrocytes
      in QUIN production is controversial. Using cytokine-stimulated cultures of human
      astrocytes, we assayed key enzymes and products of the KP. We found that human
      astrocytes lack kynurenine hydroxylase so that large amounts of kynurenine and
      the QUIN antagonist kynurenic acid were produced. However, the amounts of QUIN
      that were synthesized were subsequently completely degraded. We then showed that
      kynurenine in concentrations comparable with those produced by astrocytes led to
      significant production of QUIN by macrophages. These results suggest that
      astrocytes alone are neuroprotective by minimizing QUIN production and maximizing
      synthesis of kynurenic acid. However, it is likely that, in the presence of
      macrophages and/or microglia, astrocytes become indirectly neurotoxic by the
      production of large concentrations of kynurenine that can be secondarily
      metabolized by neighbouring or infiltrating monocytic cells to form the
      neurotoxin QUIN.

PMID- 11520906
TI  - Androgen-induced up-regulation of tubulin isoforms in neuroblastoma cells.
AB  - Androgens regulate the physiology of motor neurones both during development and
      in adult life. In particular, androgens increase the rate of axonal regeneration
      after axotomy, an effect correlated with the up-regulation of tubulin. In order
      to determine whether this was the result of a direct hormone action on neurones,
      we examined the effect of testosterone on microtubular proteins in human
      neuroblastoma SH-SY5Y cells. Treatment of proliferating SH-SY5Y cells with
      testosterone resulted in an up-regulation of alpha- and beta-tubulin. By
      contrast, no change in tubulin was observed either in cells differentiated into a
      neuronal phenotype by retinoic acid or in adrenal SW13 cells. We also show that
      an up-regulation of the ubiquitous beta(II)-tubulin and of the neurone-specific
      beta(III)-tubulin isoforms contributes to the overall increase in tubulin in
      response to androgen treatment. The increase in tubulin levels following
      testosterone treatment was abolished by co-incubation with antiandrogens,
      indicating that this effect is mediated through a classical mechanism of steroid
      action. The two microtubule-associated proteins, tau and MAP2b, remained
      unchanged following testosterone exposure. Thus, these results demonstrate that
      tubulin is a direct neuronal target of androgen regulation and suggest that
      dysregulation of tubulin expression may contribute to the pathogenesis of some
      motor neuronopathies.

PMID- 11520907
TI  - Temporal and spatial profile of caspase 8 expression and proteolysis after
      experimental traumatic brain injury.
AB  - Recent studies have demonstrated that the downstream caspases, such as caspase 3,
      act as executors of the apoptotic cascade after traumatic brain injury (TBI) in
      vivo. However, little is known about the involvement of caspases in the
      initiation phase of apoptosis, and the interaction between these initiator
      caspases (e.g. caspase 8) and executor caspases after experimental brain injuries
      in vitro and in vivo. This study investigated the temporal expression and cell
      subtype distribution of procaspase 8 and cleaved caspase 8 p20 from 1 h to 14
      days after cortical impact-induced TBI in rats. Caspase 8 messenger RNA levels,
      estimated by semiquantitaive RT-PCR, were elevated from 1 h to 72 h in the
      traumatized cortex. Western blotting revealed increased immunoreactivity for
      procaspase 8 and the proteolytically active subunit of caspase 8, p20, in the
      ipsilateral cortex from 6 to 72 h after injury, with a peak at 24 h after TBI.
      Similar to our previous studies, immunoreactivity for the p18 fragment of
      activated caspase 3 also increased in the current study from 6 to 72 h after TBI,
      but peaked at a later timepoint (48 h) as compared with proteolyzed caspase 8
      p20. Immunohistologic examinations revealed increased expression of caspase 8 in
      neurons, astrocytes and oligodendrocytes. Assessment of DNA damage using TUNEL
      identified caspase 8- and caspase 3-immunopositive cells with apoptotic-like
      morphology in the cortex ipsilateral to the injury site, and immunohistochemical
      investigations of caspase 8 and activated caspase 3 revealed expression of both
      proteases in cortical layers 2-5 after TBI. Quantitative analysis revealed that
      the number of caspase 8 positive cells exceeds the number of caspase 3 expressing
      cells up to 24 h after impact injury. In contrast, no evidence of caspase 8 and
      caspase 3 activation was seen in the ipsilateral hippocampus, contralateral
      cortex and hippocampus up to 14 days after the impact. Our results provide the
      first evidence of caspase 8 activation after experimental TBI and suggest that
      this may occur in neurons, astrocytes and oligodendrocytes. Our findings also
      suggest a contributory role of caspase 8 activation to caspase 3 mediated
      apoptotic cell death after experimental TBI in vivo.

PMID- 11520908
TI  - Neurotrophins prevent HIV Tat-induced neuronal apoptosis via a nuclear factor
      kappaB (NF-kappaB)-dependent mechanism.
AB  - HIV-1 associated dementia is thought to be caused by neuronal damage and death in
      response to the production of soluble neurotoxic factors by virally infected
      mononuclear phagocytes. These neurotoxins include HIV-1 Tat. The ability of
      neurotrophins to promote cell survival prompted us to examine whether
      neurotrophins might also be capable of opposing the pro-apoptotic effects of Tat.
      Here, we show that Tat-induced neuronal apoptosis in primary cultures of rat
      cerebellar granule cells and in neuronally differentiated human SK-N-MC cells is
      profoundly inhibited by brain-derived neurotrophic factor, nerve growth factor
      and activity-dependent neurotrophic factor nonamer peptide. These neurotrophins
      activated the transcription factor NF-kappaB, and inhibition of NF-kappaB
      activation using a super-repressor IkappaB-alpha mutant was found to block the
      survival-promoting activity of the neurotrophins. Reporter gene assays and
      immunoblot experiments revealed that the neurotrophins also up-regulated the
      expression of Bcl-2, at both the transcriptional and protein levels.
      Overexpression of the super-repressor IkappaB-alpha mutant prevented this
      induction of Bcl-2 expression. Moreover, overexpression of either Bcl-2, alone,
      or the RelA subunit of NF-kappaB, alone, protected neurons from Tat-induced
      apoptosis. These findings suggest that the activation of NF-kappaB by
      neurotrophic factors may promote survival of neurons exposed to Tat, via
      regulation of anti-apoptotic genes including Bcl-2.

PMID- 11520909
TI  - The enhancement of glucose uptake caused by the collapse of gap junction
      communication is due to an increase in astrocyte proliferation.
AB  - We have previously shown that several gap junction uncouplers increase the uptake
      of glucose in astrocytes. The aim of the present work was to study whether the
      increase in glucose uptake was a consequence of the inhibition of gap junction
      communication and the purpose of this effect. Our results show that alpha
      glycyrrhetinic acid and endothelin-1 increase the uptake of glucose in highly,
      but not in poorly, coupled astrocytes. This effect depended on connexin 43 levels
      and was abolished when the inhibition of gap junction communication was prevented
      by tolbutamide or ouabain. The inhibition of gap junctions increased the rate of
      glucose incorporation into DNA and RNA, which was inhibited by treatment with
      dehydroepiandrosterone, an inhibitor of glucose-6-phosphate dehydrogenase, the
      regulatory enzyme of the pentose phosphate pathway. The inhibition of gap
      junctions significantly increased astrocyte proliferation, which was counteracted
      by tolbutamide. These effects were not observed in poorly coupled astrocytes
      expressing low levels of connexin 43. The increase in astrocyte proliferation
      caused by gap junction inhibition was prevented when either glucose uptake or the
      pentose phosphate pathway were inhibited. We conclude that the inhibition of gap
      junction communication induces astrocyte proliferation, resulting in an
      enhancement of glucose uptake and its utilization through the pentose phosphate
      pathway to provide ribose-5-phosphate for the synthesis of nucleic acids.

PMID- 11520910
TI  - Proteasomal inhibition leads to formation of ubiquitin/alpha-synuclein
      immunoreactive inclusions in PC12 cells.
AB  - Proteasomal dysfunction has been recently implicated in the pathogenesis of
      several neurodegenerative diseases, including Parkinson's disease and diffuse
      Lewy body disease. We have developed an in vitro model of proteasomal dysfunction
      by applying pharmacological inhibitors of the proteasome, lactacystin or ZIE[O
      tBu]-A-leucinal (PSI), to dopaminergic PC12 cells. Proteasomal inhibition caused
      a dose-dependent increase in death of both naive and neuronally differentiated
      PC12 cells, which could be prevented by caspase inhibition or CPT-cAMP. A
      percentage of the surviving cells contained discrete cytoplasmic ubiquitinated
      inclusions, some of which also contained synuclein-1, the rat homologue of human
      alpha-synuclein. However the total level of synuclein-1 was not altered by
      proteasomal inhibition. The ubiquitinated inclusions were present only within
      surviving cells, and their number was increased if cell death was prevented. We
      have thus replicated, in this model system, the two cardinal pathological
      features of Lewy body diseases, neuronal death and the formation of cytoplasmic
      ubiquitinated inclusions. Our findings suggest that inclusion body formation and
      cell death may be dissociated from one another.

PMID- 11520911
TI  - Preconditioning-induced neuroprotection is mediated by reactive oxygen species
      and activation of the transcription factor nuclear factor-kappaB.
AB  - Preconditioning by a sublethal stimulus induces tolerance to a subsequent,
      otherwise lethal insult and it has been suggested that reactive oxygen species
      (ROS) are involved in this phenomenon. In the present study, we determined
      whether preconditioning activates the transcription factor nuclear factor-kappaB
      (NF-kappaB) and how this activation contributes to preconditioning-induced
      inhibition of neuronal apoptosis. Preconditioning was performed by incubating
      mixed cultures of neurons and astrocytes from neonatal rat hippocampus with
      xanthine/xanthine oxidase or FeSO4 for 15 min followed by 24 h of recovery which
      protected the neurons against subsequent staurosporine-induced (200 nM, 24 h)
      apoptosis. The cellular ROS content increased during preconditioning, but
      returned to basal levels after removal of xanthine/xanthine oxidase or FeSO4. We
      detected a transient activation of NF-kappaB 4 h after preconditioning as shown
      by immunocytochemistry, by a decrease in the protein level of IkappaBalpha as
      well as by electrophoretic mobility shift assay. Preconditioning-mediated
      neuroprotection was abolished by antioxidants, inhibitors of NF-kappaB activation
      and cycloheximide suggesting the involvement of ROS, an activation of NF-kappaB
      and de novo protein synthesis in preconditioning-mediated rescue pathways.
      Furthermore, preconditioning increased the protein level of Mn-superoxide
      dismutase which could be blocked by antioxidants, cycloheximide and kappaB decoy
      DNA. Our data suggest that inhibition of staurosporine-induced neuronal apoptosis
      by preconditioning with xanthine/xanthine oxidase or FeSO4 involves an activation
      of NF-kappaB and an increase in the protein level of Mn-superoxide dismutase.

PMID- 11520912
TI  - Stimulation of prefrontal cortex at physiologically relevant frequencies inhibits
      dopamine release in the nucleus accumbens.
AB  - The prefrontal cortex (PFC) is thought to provide an excitatory influence on the
      output of mesoaccumbens dopamine neurons. The evidence for this influence
      primarily arises from findings in the rat that chemical or high-intensity and
      high-frequency (60-200 Hz) electrical stimulations of PFC increase burst activity
      of midbrain dopamine neurons, and augment terminal release of dopamine in the
      nucleus accumbens. However, PFC neurons in animals that are engaged in PFC
      dependent cognitive tasks increase their firing frequency from a baseline of 1-3
      Hz to 7-10 Hz, suggesting that the commonly used high-frequency stimulation
      parameters of the PFC may not be relevant to the behavioral states that are
      associated with PFC activation. We investigated the influence of PFC activation
      at lower physiologically relevant frequencies on the release of dopamine in the
      nucleus accumbens. Using rapid (5-min) microdialysis measures of extracellular
      dopamine in the nucleus accumbens, we found that although PFC stimulation at 60
      Hz produces the expected increases in accumbal dopamine release, the same
      amplitude of PFC stimulation at 10 Hz significantly decreased these levels. These
      results indicate that activation of PFC, at frequencies that are associated with
      increased cognitive demand on this region, inhibits the mesoaccumbens dopamine
      system.

PMID- 11520913
TI  - Inhibition of neurite extension by overexpression of individual domains of LIM
      kinase 1.
AB  - Lin-11, Isl-1 and Mec-3 (LIM) kinases are serine/threonine kinases that
      phosphorylate cofilin, an actin depolymerizing protein. LIM kinases have a highly
      modular structure composed of two N-terminal LIM domains (LIM 1/2), a PSD-95, Dlg
      and ZO-1 (PDZ) domain and a C-terminal protein kinase domain. Here, we
      overexpressed individual domains of mouse LIM kinase 1 (LIMK1) in PC12 cells and
      investigated their effects on neurite outgrowth. Although none of the LIMK1
      domains had an effect on spontaneous neurite outgrowth, the N-terminal LIM 1/2
      domains strongly inhibited differentiation of PC12 cells after stimulation with
      both nerve growth factor (NGF) and the Rho-kinase inhibitor Y-27632. In contrast,
      the overexpressed PDZ domain reduced neurite outgrowth only when differentiation
      had been induced by Y-27632, but not by NGF. Our data suggest that the different
      non-catalytic N-terminal domains of LIMK1 contribute to the regulation of neurite
      extension by using distinct signal transduction pathways.

PMID- 11520914
TI  - Sequential organization of multiple movements: involvement of cortical motor
      areas.
AB  - Much of our normal behavior depends on the sequential execution of multiphased
      movements, or the execution of multiple movements arranged in a correct temporal
      order. This article deals with the issue of motor selection to arrange multiple
      movements in an appropriate temporal order, rather than the issue of constructing
      spatio-temporal structures in a single action. Planning, generating, and
      controlling the sequential motor behavior involves multiple cortical and
      subcortical neural structures. Studies on human subjects and nonhuman primates,
      however, have revealed that the medial motor areas in the frontal cortex and the
      basal ganglia play particularly important roles in the temporal sequencing of
      multiple movements. Cellular activity observed in the supplementary and
      presupplementary motor areas while performing specifically designed motor tasks
      suggests the way in which these areas take part in constructing the time
      structure for the sequential execution of multiple movements.

PMID- 11520915
TI  - Influence of dendritic conductances on the input-output properties of neurons.
AB  - A fundamental problem in neuroscience is understanding how a neuron transduces
      synaptic input into action potentials. The dendrites form the substrate for
      consolidating thousands of synaptic inputs and are the first stage for signal
      processing in the neuron. Traditionally, dendrites are viewed as passive
      structures whose main function is to funnel synaptic input into the soma.
      However, dendrites contain a wide variety of voltage- and time-dependent ion
      channels. When activated, the currents through these channels can alter the
      amplitude and time course of the synaptic input and under certain conditions even
      evoke all-or-none regenerative potentials. The synaptic input that ultimately
      reaches the soma is likely to be a highly transformed version of the original
      signal. Thus, a key step in understanding the relationship between synaptic input
      and neuronal firing is to elucidate the signal processing that occurs in the
      dendrites.

PMID- 11520917
TI  - Contributions of the medullary raphe and ventromedial reticular region to pain
      modulation and other homeostatic functions.
AB  - The raphe magnus is part of an interrelated region of medullary raphe and
      ventromedial reticular nuclei that project to all areas of the spinal gray.
      Activation of raphe and reticular neurons evokes modulatory effects in sensory,
      autonomic, and motor spinal processes. Two physiological types of nonserotonergic
      cells are observed in the medullary raphe and are thought to modulate spinal pain
      processing in opposing directions. Recent evidence suggests that these cells may
      modulate stimulus-evoked arousal or alerting rather than pain-evoked withdrawals.
      Nonserotonergic cells are also likely to modulate spinal autonomic and motor
      circuits involved in thermoregulation and sexual function. Medullary serotonergic
      cells have state-dependent discharge and are likely to contribute to the
      modulation of pain processing, thermoregulation, and sexual function in the
      spinal cord. The medullary raphe and ventromedial reticular region may set
      sensory, autonomic, and motor spinal circuits into configurations that are
      appropriate to the current behavioral state.

PMID- 11520918
TI  - Activation, deactivation, and adaptation in vertebrate photoreceptor cells.
AB  - Visual transduction captures widespread interest because its G-protein signaling
      motif recurs throughout nature yet is uniquely accessible for study in the
      photoreceptor cells. The light-activated currents generated at the photoreceptor
      outer segment provide an easily observed real-time measure of the output of the
      signaling cascade, and the ease of obtaining pure samples of outer segments in
      reasonable quantity facilitates biochemical experiments. A quiet revolution in
      the study of the mechanism has occurred during the past decade with the advent of
      gene-targeting techniques. These have made it possible to observe how
      transduction is perturbed by the deletion, overexpression, or mutation of
      specific components of the transduction apparatus.

PMID- 11520919
TI  - Activity-dependent spinal cord plasticity in health and disease.
AB  - Activity-dependent plasticity occurs in the spinal cord throughout life. Driven
      by input from the periphery and the brain, this plasticity plays an important
      role in the acquisition and maintenance of motor skills and in the effects of
      spinal cord injury and other central nervous system disorders. The responses of
      the isolated spinal cord to sensory input display sensitization, long-term
      potentiation, and related phenomena that contribute to chronic pain syndromes;
      they can also be modified by both classical and operant conditioning protocols.
      In animals with transected spinal cords and in humans with spinal cord injuries,
      treadmill training gradually modifies the spinal cord so as to improve
      performance. These adaptations by the isolated spinal cord are specific to the
      training regimen and underlie new approaches to restoring function after spinal
      cord injury. Descending inputs from the brain that occur during normal
      development, as a result of supraspinal trauma, and during skill acquisition
      change the spinal cord. The early development of adult spinal cord reflex
      patterns is driven by descending activity; disorders that disrupt descending
      activity later in life gradually change spinal cord reflexes. Athletic training,
      such as that undertaken by ballet dancers, is associated with gradual alterations
      in spinal reflexes that appear to contribute to skill acquisition. Operant
      conditioning protocols in animals and humans can produce comparable reflex
      changes and are associated with functional and structural plasticity in the
      spinal cord, including changes in motoneuron firing threshold and axonal
      conduction velocity, and in synaptic terminals on motoneurons. The corticospinal
      tract has a key role in producing this plasticity. Behavioral changes produced by
      practice or injury reflect the combination of plasticity at multiple spinal cord
      and supraspinal sites. Plasticity at multiple sites is both necessary-to insure
      continued performance of previously acquired behaviors-and inevitable-due to the
      ubiquity of the capacity for activity-dependent plasticity in the central nervous
      system. Appropriate induction and guidance of activity-dependent plasticity in
      the spinal cord is an essential component of new therapeutic approaches aimed at
      maximizing function after spinal cord injury or restoring function to a newly
      regenerated spinal cord. Because plasticity in the spinal cord contributes to
      skill acquisition and because the spinal cord is relatively simple and
      accessible, this plasticity is a logical and practical starting point for
      studying the acquisition and maintenance of skilled behaviors.

PMID- 11520920
TI  - Quantitative genetics and mouse behavior.
AB  - Quantitative differences are observed for most complex behavioral and
      pharmacological traits within any population. Both environmental and genetic
      influences regulate such individual differences. The mouse has proven to be a
      superb model in which to investigate the genetic basis for quantitative
      differences in complex behaviors. Genetically defined populations of mice,
      including inbred strains, heterogeneous stocks, and selected lines, have been
      used effectively to document these genetic differences. Recently, quantitative
      trait loci methods have been applied to map the chromosomal regions that regulate
      variation with the goal of eventually identifying the gene polymorphisms that
      reside in these regions.

PMID- 11520921
TI  - Early anterior/posterior patterning of the midbrain and cerebellum.
AB  - Transplantation studies performed in chicken embryos indicated that early
      anterior/posterior patterning of the vertebrate midbrain and cerebellum might be
      regulated by an organizing center at the junction between the midbrain and
      hindbrain. More than a decade of molecular and genetic studies have shown that
      such an organizer is indeed central to development of the midbrain and anterior
      hindbrain. Furthermore, a complicated molecular network that includes multiple
      positive and negative feedback loops underlies the establishment and refinement
      of a mid/hindbrain organizer, as well as the subsequent function of the
      organizer. In this review, we first introduce the expression patterns of the
      genes known to be involved in this patterning process and the quail-chick
      transplantation experiments that have provided the foundation for understanding
      the genetic pathways regulating mid/hindbrain patterning. Subsequently, we
      discuss the molecular genetic studies that have revealed the roles for many genes
      in normal early patterning of this region. Finally, some of the remaining
      questions and future directions are discussed.

PMID- 11520922
TI  - Neurobiology of Pavlovian fear conditioning.
AB  - Learning the relationships between aversive events and the environmental stimuli
      that predict such events is essential to the survival of organisms throughout the
      animal kingdom. Pavlovian fear conditioning is an exemplar of this form of
      learning that is exhibited by both rats and humans. Recent years have seen an
      incredible surge in interest in the neurobiology of fear conditioning. Neural
      circuits underlying fear conditioning have been mapped, synaptic plasticity in
      these circuits has been identified, and biochemical and genetic manipulations are
      beginning to unravel the molecular machinery responsible for the storage of fear
      memories. These advances represent an important step in understanding the neural
      substrates of a rapidly acquired and adaptive form of associative learning and
      memory in mammals.

PMID- 11520916
TI  - Neurotrophins: roles in neuronal development and function.
AB  - Neurotrophins regulate development, maintenance, and function of vertebrate
      nervous systems. Neurotrophins activate two different classes of receptors, the
      Trk family of receptor tyrosine kinases and p75NTR, a member of the TNF receptor
      superfamily. Through these, neurotrophins activate many signaling pathways,
      including those mediated by ras and members of the cdc-42/ras/rho G protein
      families, and the MAP kinase, PI-3 kinase, and Jun kinase cascades. During
      development, limiting amounts of neurotrophins function as survival factors to
      ensure a match between the number of surviving neurons and the requirement for
      appropriate target innervation. They also regulate cell fate decisions, axon
      growth, dendrite pruning, the patterning of innervation and the expression of
      proteins crucial for normal neuronal function, such as neurotransmitters and ion
      channels. These proteins also regulate many aspects of neural function. In the
      mature nervous system, they control synaptic function and synaptic plasticity,
      while continuing to modulate neuronal survival.

PMID- 11520923
TI  - alpha-Latrotoxin and its receptors: neurexins and CIRL/latrophilins.
AB  - alpha-Latrotoxin, a potent neurotoxin from black widow spider venom, triggers
      synaptic vesicle exocytosis from presynaptic nerve terminals. alpha-Latrotoxin is
      a large protein toxin (120 kDa) that contains 22 ankyrin repeats. In stimulating
      exocytosis, alpha-latrotoxin binds to two distinct families of neuronal cell
      surface receptors, neurexins and CLs (Cirl/latrophilins), which probably have a
      physiological function in synaptic cell adhesion. Binding of alpha-latrotoxin to
      these receptors does not in itself trigger exocytosis but serves to recruit the
      toxin to the synapse. Receptor-bound alpha-latrotoxin then inserts into the
      presynaptic plasma membrane to stimulate exocytosis by two distinct transmitter
      specific mechanisms. Exocytosis of classical neurotransmitters (glutamate, GABA,
      acetylcholine) is induced in a calcium-independent manner by a direct
      intracellular action of alpha-latrotoxin, while exocytosis of catecholamines
      requires extracellular calcium. Elucidation of precisely how alpha-latrotoxin
      works is likely to provide major insight into how synaptic vesicle exocytosis is
      regulated, and how the release machineries of classical and catecholaminergic
      neurotransmitters differ.

PMID- 11520924
TI  - Imaging and coding in the olfactory system.
AB  - Functional imaging methods permit analysis of neuronal systems in which activity
      is broadly distributed in time and space. In the olfactory system the dimensions
      that describe odorant stimuli in "odorant space" are still poorly defined. One
      way of trying to characterize the attributes of this space is to examine the ways
      in which its dimensions are encoded by the neurons and circuits making up the
      system and to compare these responses with physical-chemical attributes of the
      stimuli and with the output behavior of the animal. For documenting distributed
      events as they occur, imaging methods are among the few tools available. We are
      still in the early stages of this analysis; however, a number of recent studies
      have contributed new information to our understanding of the odorant coding
      problem. This paper describes imaging results in the context of other data that
      have contributed to our understanding of how odors are encoded by the peripheral
      olfactory pathway.

PMID- 11520925
TI  - The role of the cerebellum in voluntary eye movements.
AB  - In general the cerebellum is crucial for the control but not the initiation of
      movement. Voluntary eye movements are particularly useful for investigating the
      specific mechanisms underlying cerebellar control because they are precise and
      their brain-stem circuitry is already well understood. Here we describe single
      unit and inactivation data showing that the posterior vermis and the caudal
      fastigial nucleus, to which it projects, provide a signal during horizontal
      saccades to make them fast, accurate, and consistent. The caudal fastigial
      nucleus also is necessary for the recovery of saccadic accuracy after actual or
      simulated neural or muscular damage causes horizontal saccades to be dysmetric.
      Saccade-related activity in the interpositus nucleus is related to vertical
      saccades. Both the caudal fastigial nucleus and the flocculus/paraflocculus are
      necessary for the normal smooth eye movements that pursue a small moving spot. By
      using eye movements, we have begun to uncover basic principles that give us
      insight into how the cerebellum may control movement in general.

PMID- 11520926
TI  - Role of the reelin signaling pathway in central nervous system development.
AB  - The neurological mutant mouse reeler has played a critical role in the evolution
      of our understanding of normal brain development. From the earliest neuroanatomic
      studies of reeler, it was anticipated that the characterization of the gene
      responsible would elucidate important molecular and cellular principles governing
      cell positioning and the formation of synaptic circuits in the developing brain.
      Indeed, the identification of reelin has challenged many of our previous notions
      and has led to a new vision of the events involved in the migration of neurons.
      Several neuronal populations throughout the brain secrete Reelin, which binds to
      transmembrane receptors located on adjacent cells triggering a tyrosine kinase
      cascade. This allows neurons to complete migration and adopt their ultimate
      positions in laminar structures in the central nervous system. Recent studies
      have also suggested a role for the Reelin pathway in axonal branching,
      synaptogenesis, and pathology underlying neurodegeneration.

PMID- 11520927
TI  - Human brain malformations and their lessons for neuronal migration.
AB  - The developmental steps required to build a brain have been recognized as a
      distinctive sequence since the turn of the twentieth century. As marking tools
      for experimental embryology emerged, the cellular events of cortical histogenesis
      have been intensively scrutinized. On this rich backdrop, molecular genetics
      provides the opportunity to play out the molecular programs that orchestrate
      these cellular events. Genetic studies of human brain malformation have proven a
      surprising source for finding the molecules that regulate CNS neuronal migration.
      These studies also serve to relate the significance of genes first identified in
      murine species to the more complex human brain. The known genetic repertoire that
      is special to neuronal migration in brain has rapidly expanded over the past five
      years, making this an appropriate time to take stock of the emerging picture. We
      do this from the perspective of human brain malformation syndromes, noting both
      what is now known of their genetic bases and what remains to be discovered.

PMID- 11520928
TI  - Morphological changes in dendritic spines associated with long-term synaptic
      plasticity.
AB  - Dendritic spines are morphological specializations that receive synaptic inputs
      and compartmentalize calcium. In spite of a long history of research, the
      specific function of spines is still not well understood. Here we review the
      current status of the relation between morphological changes in spines and
      synaptic plasticity. Since Cajal and Tanzi proposed that changes in the structure
      of the brain might occur as a consequence of experience, the search for the
      morphological correlates of learning has constituted one of the central questions
      in neuroscience. Although there are scores of studies that encompass this wide
      field in many species, in this review we focus on experimental work that has
      analyzed the morphological consequences of hippocampal long-term potentiation
      (LTP) in rodents. Over the past two decades many studies have demonstrated
      changes in the morphology of spines after LTP, such as enlargements of the spine
      head and shortenings of the spine neck. Biophysically, these changes translate
      into an increase in the synaptic current injected at the spine, as well as
      shortening of the time constant for calcium compartmentalization. In addition,
      recent online studies using time-lapse imaging have reported increased
      spinogenesis. The currently available data show a strong correlation between
      synaptic plasticity and morphological changes in spines, although at the same
      time, there is no evidence that these morphological changes are necessary or
      sufficient for the induction or maintenance of LTP. Still, they highlight once
      more how form and function go hand in hand in the central nervous system.

PMID- 11520929
TI  - Stopping time: the genetics of fly and mouse circadian clocks.
AB  - Forward genetic analyses in flies and mice have uncovered conserved
      transcriptional feedback loops at the heart of circadian pacemakers. Conserved
      mechanisms of posttranslational regulation, most notably phosphorylation, appear
      to be important for timing feedback. Transcript analyses have indicated that
      circadian clocks are not restricted to neurons but are found in several tissues.
      Comparisons between flies and mice highlight important differences in molecular
      circuitry and circadian organization. Future studies of pacemaker mechanisms and
      their control of physiology and behavior will likely continue to rely on forward
      genetics.

PMID- 11520930
TI  - Neurodegenerative tauopathies.
AB  - The defining neuropathological characteristics of Alzheimer's disease are
      abundant filamentous tau lesions and deposits of fibrillar amyloid beta peptides.
      Prominent filamentous tau inclusions and brain degeneration in the absence of
      beta-amyloid deposits are also hallmarks of neurodegenerative tauopathies
      exemplified by sporadic corticobasal degeneration, progressive supranuclear
      palsy, and Pick's disease, as well as by hereditary frontotemporal dementia and
      parkinsonism linked to chromosome 17 (FTDP-17). Because multiple tau gene
      mutations are pathogenic for FTDP-17 and tau polymorphisms appear to be genetic
      risk factors for sporadic progressive supranuclear palsy and corticobasal
      degeneration, tau abnormalities are linked directly to the etiology and
      pathogenesis of neurodegenerative disease. Indeed, emerging data support the
      hypothesis that different tau gene mutations are pathogenic because they impair
      tau functions, promote tau fibrillization, or perturb tau gene splicing, thereby
      leading to formation of biochemically and structurally distinct aggregates of
      tau. Nonetheless, different members of the same kindred often exhibit diverse
      FTDP-17 syndromes, which suggests that additional genetic or epigenetic factors
      influence the phenotypic manifestations of neurodegenerative tauopathies.
      Although these and other hypothetical mechanisms of neurodegenerative tauopathies
      remain to be tested and validated, transgenic models are increasingly available
      for this purpose, and they will accelerate discovery of more effective therapies
      for neurodegenerative tauopathies and related disorders, including Alzheimer's
      disease.

PMID- 11520931
TI  - Maternal care, gene expression, and the transmission of individual differences in
      stress reactivity across generations.
AB  - Naturally occurring variations in maternal care alter the expression of genes
      that regulate behavioral and endocrine responses to stress, as well as
      hippocampal synaptic development. These effects form the basis for the
      development of stable, individual differences in stress reactivity and certain
      forms of cognition. Maternal care also influences the maternal behavior of female
      offspring, an effect that appears to be related to oxytocin receptor gene
      expression, and which forms the basis for the intergenerational transmission of
      individual differences in stress reactivity. Patterns of maternal care that
      increase stress reactivity in offspring are enhanced by stressors imposed on the
      mother. These findings provide evidence for the importance of parental care as a
      mediator of the effects of environmental adversity on neural development.

PMID- 11520932
TI  - Natural image statistics and neural representation.
AB  - It has long been assumed that sensory neurons are adapted, through both
      evolutionary and developmental processes, to the statistical properties of the
      signals to which they are exposed. Attneave (1954)Barlow (1961) proposed that
      information theory could provide a link between environmental statistics and
      neural responses through the concept of coding efficiency. Recent developments in
      statistical modeling, along with powerful computational tools, have enabled
      researchers to study more sophisticated statistical models for visual images, to
      validate these models empirically against large sets of data, and to begin
      experimentally testing the efficient coding hypothesis for both individual
      neurons and populations of neurons.

PMID- 11520933
TI  - Nerve growth factor signaling, neuroprotection, and neural repair.
AB  - Nerve growth factor (NGF) was discovered 50 years ago as a molecule that promoted
      the survival and differentiation of sensory and sympathetic neurons. Its roles in
      neural development have been characterized extensively, but recent findings point
      to an unexpected diversity of NGF actions and indicate that developmental effects
      are only one aspect of the biology of NGF. This article considers expanded roles
      for NGF that are associated with the dynamically regulated production of NGF and
      its receptors that begins in development, extends throughout adult life and
      aging, and involves a surprising variety of neurons, glia, and nonneural cells.
      Particular attention is given to a growing body of evidence that suggests that
      among other roles, endogenous NGF signaling subserves neuroprotective and repair
      functions. The analysis points to many interesting unanswered questions and to
      the potential for continuing research on NGF to substantially enhance our
      understanding of the mechanisms and treatment of neurological disorders.

PMID- 11520934
TI  - Flies, genes, and learning.
AB  - Flies can learn. For the past 25 years, researchers have isolated mutants,
      engineered mutants with transgenes, and tested likely suspect mutants from other
      screens for learning ability. There have been notable surprises-conventional
      second messenger systems co-opted for intricate associative learning tasks, two
      entirely separate forms of long-term memory, a cell-adhesion molecule that is
      necessary for short-term memory. The most recent surprise is the mechanistic
      kinship revealed between learning and addictive drug response behaviors in flies.
      The flow of new insight is likely to quicken with the completion of the fly
      genome and the arrival of more selective methods of gene expression.

PMID- 11520935
TI  - Medical education, evidence-based medicine, and the disqualification of physician
      scientists.

PMID- 11520936
TI  - Estrogen synthetase (aromatase) immunohistochemistry reveals concordance between
      avian and rodent limbic systems and hypothalami.
AB  - During amniote evolution, an early divergence occurred about 300 million years
      ago between the reptilian lines leading to the appearance of birds (anapsids) and
      mammals (synapsids). The different functional requirements of these vertebrate
      groups have involved divergent evolution of their brains. Even superficial
      examination reveals major anatomical differences between mammalian and avian
      brains, such as extensive development of the optic lobes and cerebellum in birds
      and a highly developed cortex in mammals. It has been nearly impossible to
      identify avian homologs of some mammalian brain regions by standard morphological
      criteria. This has long frustrated efforts at clarifying hypotheses regarding the
      anatomical location, field size, and regulation of brain functions shared between
      these two classes, despite the certainty that the principles of neurobiology
      apply equally at the cellular level in both groups. In an effort to remove this
      barrier, we have sought markers of common function that despite apparent
      anatomical dissimilarity, can allow recognition of homologous brain structures.
      We illustrate here how comparative analysis of the distribution of the steroid
      metabolizing enzyme estrogen synthetase (aromatase) may help to understand the
      differences and similarities in the limbic system and hypothalamus of birds and
      mammals.

PMID- 11520937
TI  - The role of thrombospondin-1 in tumor progression.
AB  - The role of thrombospondin-1 (TSP-1) in tumor progression is both complex and
      controversial. It is clear from the literature that the function of TSP-1 in
      malignancy depends on the presence of other factors and the level of TSP-1
      expression in the tumor tissue. High levels of TSP-1 secreted by tumors, which
      were engineered to overexpress TSP-1, inhibit tumor growth, while anti-sense
      inhibition of TSP-1 production in certain tumors also inhibits growth. Clearly,
      the presence of other factors in these experimental systems must be important.
      The role of TSP-1 in angiogenesis also depends on the levels of TSP-1, the
      presence and level of angiogenic stimulators such as basic fibroblast growth
      factor (bFGF), and the localization of TSP-1 in the tissue. Matrix-bound TSP-1
      promotes capillary tube formation in the rat aorta model of angiogenesis, while
      TSP-1 inhibits bFGF- induced angiogenesis in the rat cornea model. The inhibitory
      effect also depends on the proteolytic state of TSP-1 since the amino terminus
      promotes angiogenesis in the cornea model, while the remaining 140-kDa fragment
      inhibits bFGF-induced angiogenesis. Both the stimulatory and inhibitory effects
      of TSP-1 are likely due to upregulation of matrix-degrading enzymes and their
      inhibitors. These enzymes are critical for maintaining optimal matrix turnover
      during angiogenesis. These varied TSP-1-dependent mechanisms offer new targets
      for the development of anti-angiogenic therapeutics for the treatment of a
      variety of cancers, as well as other pathologies involving inappropriate
      angiogenesis such as diabetic retinopathy.

PMID- 11520938
TI  - Possible role of retinoids in hepatitis B virus-associated liver damage.
AB  - Liver damage following hepatitis B virus (HBV) infection may be due to the action
      of retinoids as modulators of viral replication. The reduced rate of survival of
      liver grafts in patients with HBV infection could also be due to the continued
      presence of the virus, stimulated by retinoids in the graft tissue. Subject to
      obtaining empirical support for this hypothesis, the use of retinoid-blocking
      agents could be explored to reduce the risk of liver damage in HBV infection and
      to enhance the survival of liver grafts. Continued use of such agents may need to
      be used in conjunction with anti-viral modalities such as HBV hyperimmune
      globulin and lamivudine to prevent recurrent liver damage and to increase the
      long-term viability of the graft.

PMID- 11520939
TI  - Hormonal modulation of food intake in response to low leptin levels induced by
      hypergravity.
AB  - A loss in fat mass is a common response to centrifugation and it results in low
      circulating leptin concentrations. However, rats adapted to hypergravity are
      euphagic. The focus of this study was to examine leptin and other peripheral
      signals of energy balance in the presence of a hypergravity-induced loss of fat
      mass and euphagia. Male Sprague-Dawley rats were centrifuged for 14 days at
      gravity levels of 1.25, 1.5, or 2 G, or they remained stationary at 1 G. Urinary
      catecholamines, urinary corticosterone, food intake, and body mass were measured
      on Days 11 to 14. Plasma hormones and epididymal fat pad mass were measured on
      Day 14. Mean body mass of the 1.25, 1.5, and 2 G groups were significantly (P <
      0.05) lower than controls, and no differences were found in food intake
      (g/day/100 g body mass) between the hypergravity groups and controls. Epididymal
      fat mass was 14%, 14%, and 21% lower than controls in the 1.25, 1.5, and 2.0 G
      groups, respectively. Plasma leptin was significantly reduced from controls by
      46%, 45%, and 65% in the 1.25, 1.5, and 2 G groups, respectively. Plasma insulin
      was significantly lower in the 1.25, 1.5, and 2.0 G groups than controls by 35%,
      38%, and 33%. No differences were found between controls and hypergravity groups
      in urinary corticosterone. Mean urinary epinephrine was significantly higher in
      the 1.5 and 2.0 G groups than in controls. Mean urinary norepinephrine was
      significantly higher in the 1.25, 1.5 and 2.0 G groups than in controls.
      Significant correlations were found between G load and body mass, fat mass,
      leptin, urinary epinephrine, and norepinephrine. During hypergravity exposure,
      maintenance of food intake is the result of a complex relationship between
      multiple pathways, which abates the importance of leptin as a primary signal.

PMID- 11520940
TI  - On the mechanism of hemozoin production in malaria parasites: activated
      erythrocyte membranes promote beta-hematin synthesis.
AB  - The ferriprotoporphyrin IX (FP) molecules released by intraerythrocytic malaria
      parasites during hemoglobin digestion are converted to beta-hematin and are
      stored in the parasites' food vacuoles. It has been demonstrated in cell-free
      medium that the incorporation of FP into beta-hematin under physiological
      conditions requires a catalyst from parasite lysates or pre-formed beta-hematin.
      In the present studies, lysates of Plasmodium falciparum-infected erythrocytes
      were suspended in 1 M NaOH and were washed with phosphate buffer, pH 7.6. When
      the cell extracts were incubated with hematin in 0.5 M sodium acetate buffer, pH
      5, for 20 hr at 37 degrees C, a large quantity of beta-hematin was formed. To
      determine whether parasite components were necessary for the beta-hematin
      formation, normal erythrocyte ghosts were similarly treated with 1 M NaOH and
      then incubated with hematin. In repeated experiments it was found that, on the
      average, 70% of the hematin was converted to beta-hematin. Membranes treated with
      HCl or CH(3)COOH also promoted the formation of beta-hematin, while untreated
      membranes were ineffective. The possibility that metabolic activities in the food
      vacuoles of malaria parasites may activate membrane fragments, from hemoglobin
      vesicles, to promote beta-hematin formation is discussed in this paper.

PMID- 11520941
TI  - Telomerase activity in Kaposi's sarcoma, squamous cell carcinoma, and basal cell
      carcinoma.
AB  - Patients with acquired immune deficiency syndrome (AIDS) often develop Kaposi's
      sarcoma (KS), an unusual skin tumor. The malignant nature of KS has long been
      disputed. Telomerase activity that maintains telomere length and ensures
      chromosomal stability, a frequently appearing marker in human malignancies, has
      been proposed to play a critical role in supporting continued cell growth, hence
      formation of tumors. We examined telomerase activity in tissue extracts from 22
      KS, 10 squamous cell carcinoma (SCC), and 22 basal cell carcinoma (BCC) using the
      telomeric repeat amplification protocol (TRAP). All of the tumor tissues were
      previously cryopreserved at -80 degrees C. In this study, all tumor samples
      tested were positive for telomerase activity. Consistent with the presence of the
      enzyme activity, the skin tumors had relatively long telomeres. Inhibitors in the
      tissue extracts of some samples needed to be diluted or extracted by phenol
      before the enzyme activity was detected in the TRAP assay. All KS as well as two
      other skin carcinoma samples revealed positive telomerase activity. Our finding
      supports telomerase's role in tumor cell immortality and suggests the true
      neoplastic nature of KS.

PMID- 11520942
TI  - Cholesterol-lowering effects of maitake (Grifola frondosa) fiber, shiitake
      (Lentinus edodes) fiber, and enokitake (Flammulina velutipes) fiber in rats.
AB  - The effects of mushroom fibers on serum cholesterol and hepatic low-density
      lipoprotein (LDL) receptor mRNA in rats were investigated. Rats were fed a
      cholesterol-free diet with 50 g/kg cellulose powder (CP), 50 g/kg maitake
      (Grifola frondosa) fiber (MAF), 50 g/kg shiitake (Lentinus edodes) fiber (SF), or
      50 g/kg enokitake (Flammulina velutipes) fiber (EF) for 4 weeks. There were no
      significant differences in the body weight, food intake, liver weight, cecum
      weight, and cecum pH among the groups. Cecal acetic acid, butyric acid, and total
      short-chain fatty acid (SCFA) concentrations in the SF and EF groups were
      significantly higher than those in the other groups. The serum total cholesterol
      concentration in the CP group was significantly higher than that in the MAF and
      EF groups. The very LDL (VLDL) + intermediate-density lipoprotein (IDL) + LDL
      cholesterol concentration in the CP group was significantly higher than that in
      the MAF, SF, and EF groups, whereas the high-density lipoprotein (HDL)
      cholesterol concentration in the EF group was significantly lower than that in
      the other groups at the end of the 4-week feeding period. The hepatic LDL
      receptor mRNA level in the EF group was significantly higher than that in the CP
      group. The fecal cholesterol excretion in the MAF, SF, and EF groups was
      significantly higher than that in the CP group. The results of this study
      demonstrate that MAF and EF lowered the serum total cholesterol level by
      enhancement of fecal cholesterol excretion, and in particular, by enhancement of
      hepatic LDL receptor mRNA in EF group.

PMID- 11520943
TI  - Retinoic acid combined with neurotrophin-3 enhances the survival and neurite
      outgrowth of embryonic sympathetic neurons.
AB  - Both nerve growth factor (NGF) and neurotrophin-3 (NT-3) are necessary for the
      survival of embryonic sympathetic neurons in vivo. All-trans retinoic acid (atRA)
      has been shown to promote neurite outgrowth and long-term survival of chick
      embryonic sympathetic neurons cultured in the presence of NGF. The present study
      shows that atRA can also potentiate the survival and neurite outgrowth-promoting
      activities of NT-3. This was accomplished by enhancing the survival of existing
      neurons, as cell proliferation was unaffected by exposure to atRA. atRA also
      enhanced neurite outgrowth of the NT-3-treated cells; however, the neurites
      appeared thicker and less branched than cells treated with atRA in combination
      with NGF. Using a quantitative PCR assay, trkA and p75(NTR) mRNAs, but not trkC
      mRNA, were increased ( approximately 1.5- to 2-fold) after 72 and 48 hr of
      exposure of the cultures to atRA, respectively. The atRA-induced increase in trkA
      mRNA may play a role in the enhanced survival of neurons cultured in the presence
      of either NGF or NT-3, as both neurotrophins have been shown to signal through
      this receptor. The time course of these mRNA changes would indicate that atRA
      does not regulate the neurotrophin receptor mRNA directly, rather, intervening
      gene transcription is required. Thus, during development, atRA may play a role in
      fine-tuning embryonic responsiveness to both NT-3 and NGF.

PMID- 11520944
TI  - Vagal influence on compensatory ovarian growth is important only briefly after
      hemicastration.
AB  - Hemicastration induces growth of the remnant ovary in the rat. As evidenced by
      the effects of total abdominal vagotomy, vagal innervation markedly influences
      this compensatory ovarian growth. In the present experiments, vagotomy inhibited
      compensatory ovarian growth when performed immediately after hemicastration, but
      not when delayed until 4.5 hr after hemicastration. Brief exposure of
      subdiaphragmal portion of the vagi nerves to 2% lidocaine shortly before
      hemicastration also inhibited compensatory growth. Fifteen minutes after
      hemicastration, markedly elevated tissue concentrations of cyclic adenosine
      monophosphate (cAMP) were recorded in the remnant ovaries. This accumulation of
      cAMP was inhibited by vagotomy that preceded hemicastration, as well as by
      lidocaine pretreatment of the vagi nerves, and partly by vagotomy that followed
      10 min after hemicastration. At 5 hr after hemicastration, tissue cAMP
      concentrations in the remnant ovaries were not elevated and were not affected by
      vagotomy. The present results suggest that vagal influence on the compensatory
      ovarian growth is important only during a short period of time after
      hemicastration (apparently shorter than 4.5 hr), and that it, at least briefly
      after hemicastration, includes neural input to the ovary.

PMID- 11520945
TI  - Dehydroepiandrosterone alters Zucker rat soleus and cardiac muscle lipid
      profiles.
AB  - High levels of serum free fatty acids (FFA) and lower proportions of
      polyunsaturated (PU) FAs, specifically arachidonic acid (AA), are common in
      obesity, insulin resistance (IR), and type 2 diabetes mellitus.
      Dehydrepiandrosterone (DHEA) decreases body fat content, dietary fat consumption,
      and insulin levels in obese Zucker rats (ZR), a genetic model of human youth
      onset obesity and type 2 diabetes. This study was conducted to investigate DHEA's
      effects on lean and obese ZR serum FFA levels and total lipid (TL) FA profiles in
      heart and soleus muscle. We postulated that DHEA alters serum FFA levels and
      tissue TL FA profiles of obese ZR so that they resemble the levels and profiles
      of lean ZR. If so, DHEA may directly or indirectly alter tissue lipids, FFA flux,
      and perhaps lower IR in obese ZR. Lean and obese male ZR were divided into six
      groups with 10 animals in each: obese ad libitum control, obese pair-fed, obese
      DHEA, lean ad libitum control, lean pair-fed, and lean DHEA. All animals had ad
      libitum access to a diet whose calories were 50% fat, 30% carbohydrate, and 20%
      protein. Only the diets of the DHEA treatment groups were supplemented with 0.6%
      DHEA. Pair-fed groups were given the average number of calories per day consumed
      by their corresponding DHEA group, and ad libitum groups had 24-h access to the
      DHEA-free diet. Serum FFA levels and heart and soleus TL FA profiles were
      measured. Serum FFA levels were higher in obese (approximately 1 mmol/L) compared
      to lean (approximately 0.6 mmol/L) ZR, regardless of group. In hearts,
      monounsaturated (MU) FA were greater and PU FA were proportionally lower in obese
      compared to the lean rats. In soleus, saturated and MU FA were greater and PU FA
      were proportionally lower in the obese compared to the lean rats. DHEA groups
      displayed significantly increased proportions of TL AA and decreased oleic acid
      in both muscle types. Mechanisms by which DHEA alters TL FA profiles are a
      reflection of changes occurring within specific lipid fractions such as FFA,
      phospholipid, and triglyceride. This study provides initial insights into DHEA's
      lipid altering effects.

PMID- 11520946
TI  - Effects of hypergravity exposure on the developing central nervous system:
      possible involvement of thyroid hormone.
AB  - The present study examined the effects of hypergravity exposure on the developing
      brain and specifically explored the possibility that these effects are mediated
      by altered thyroid status. Thirty-four timed-pregnant Sprague-Dawley rats were
      exposed to continuous centrifugation at 1.5 G (HG) from gestational Day 11 until
      one of three key developmental points: postnatal Day (P) 6, P15, or P21 (10
      pups/dam: 5 males/5 females). During the 32-day centrifugation, stationary
      controls (SC, n = 25 dams) were housed in the same room as HG animals. Neonatal
      body, forebrain, and cerebellum mass and neonatal and maternal thyroid status
      were assessed at each time point. The body mass of centrifuged neonates was
      comparatively lower at each time point. The mass of the forebrain and the mass of
      the cerebellum were maximally reduced in hypergravity-exposed neonates at P6 by
      15.9% and 25.6%, respectively. Analysis of neonatal plasma suggested a transient
      hypothyroid status, as indicated by increased thyroid stimulating hormone (TSH)
      level (38.6%) at P6, while maternal plasma TSH levels were maximally elevated at
      P15 (38.9%). Neither neonatal nor maternal plasma TH levels were altered,
      suggesting a moderate hypothyroid condition. Thus, continuous exposure of the
      developing rats to hypergravity during the embryonic and neonatal periods has a
      highly significant effect on the developing forebrain and cerebellum and neonatal
      thyroid status (P < 0.05, Bonferroni corrected). These data are consistent with
      the hypothesized role of the thyroid hormone in mediating the effect of
      hypergravity in the developing central nervous system and begin to define the
      role of TH in the overall response of the developing organism to altered gravity.

PMID- 11520947
TI  - Matrix metalloproteinases-2 and 9 do not play a role in the growth of
      preneoplastic liver lesions in F344 rats.
AB  - Matrix metalloproteinases- (MMPs) 2 and 9 (gelatinases A and B) have been
      implicated in tumor invasion and metastasis, and recent studies have shown
      increased levels of these enzymes during recovery from partial hepatectomy (PH)
      in rats. F344 rats are highly susceptible to the growth of glutathione S
      transferase 7-7- (GST 7-7) positive preneoplastic liver lesions promoted using
      the modified resistant hepatocyte (RH) protocol. Since the RH protocol consists
      of 2-acetylaminofluorene (2-AAF) followed by a PH, we reasoned that MMP-2 and -9
      might be critical for the growth of lesions. Using gelatin zymography, we
      examined the expression of these enzymes in the livers of F344 rats treated with
      the RH protocol and sacrificed on Days 2, 4, 7, 14, and 21 after 2-AAF/PH. We
      found increases in both pro- and active MMP-2 and -9 over baseline levels, with
      the highest levels occurring on Day 7 post-PH. Also, a 54-kDa band, likely to be
      proMMP-1, was elevated in a pattern similar to MMP-2 and -9. In contrast to F344
      rats, identically treated Copenhagen rats that are highly resistant to promotion
      of liver lesion growth using the RH protocol had significantly lower levels of
      proMMP-1 and -2. To test the importance of these MMPs to the growth of liver
      lesions, F344 rats that had been initiated with diethylnitrosamine were treated
      using the RH protocol. They then received either the MMP inhibitor batimastat (30
      mg/kg, intraperitoneally) or vehicle alone daily from Day 3 to 20 post-PH and
      were sacrificed on Day 21. There were no differences in the percentage of liver
      volume occupied by GST 7-7-positive lesions (19.1 +/- 4.84 vs 19.4 +/- 3.31,
      treated versus vehicle, mean +/- SEM) or liver weight as a percentage of body
      weight (4.11% +/- 0.15 vs 4.07% +/- 0.18, treated versus vehicle, mean +/- SEM)
      between the treated and control groups. Treatment of rats with batimastat clearly
      did not affect lesion growth or liver regeneration following the RH protocol.
      These results suggest that increases in gelatinase expression during the RH
      protocol are a result of the promotional stimulus rather than a mechanism by
      which 2-AAF/PH causes lesion growth.

PMID- 11520948
TI  - The organic content of the Tagish Lake meteorite.
AB  - The Tagish Lake meteorite fell last year on a frozen lake in Canada and may
      provide the most pristine material of its kind. Analyses have now shown this
      carbonaceous chondrite to contain a suite of soluble organic compounds
      (approximately 100 parts per million) that includes mono- and dicarboxylic acids,
      dicarboximides, pyridine carboxylic acids, a sulfonic acid, and both aliphatic
      and aromatic hydrocarbons. The insoluble carbon exhibits exclusive aromatic
      character, deuterium enrichment, and fullerenes containing "planetary" helium and
      argon. The findings provide insight into an outcome of early solar chemical
      evolution that differs from any seen so far in meteorites.

PMID- 11520949
TI  - Genetic basis for activity differences between vancomycin and glycolipid
      derivatives of vancomycin.
AB  - Small molecules that affect specific protein functions can be valuable tools for
      dissecting complex cellular processes. Peptidoglycan synthesis and degradation is
      a process in bacteria that involves multiple enzymes under strict temporal and
      spatial regulation. We used a set of small molecules that inhibit the
      transglycosylation step of peptidoglycan synthesis to discover genes that help to
      regulate this process. We identified a gene responsible for the susceptibility of
      Escherichia coli cells to killing by glycolipid derivatives of vancomycin, thus
      establishing a genetic basis for activity differences between these compounds and
      vancomycin.

PMID- 11520950
TI  - The Tagish Lake meteorite: a possible sample from a D-type asteroid.
AB  - A new type of carbonaceous chondrite, the Tagish Lake meteorite, exhibits a
      reflectance spectrum similar to spectra observed from the D-type asteroids, which
      are relatively abundant in the outer solar system beyond the main asteroid belt
      and have been inferred to be more primitive than any known meteorite. Until the
      Tagish Lake fall, these asteroids had no analog in the meteorite collections. The
      Tagish Lake meteorite is a carbon-rich (4 to 5 weight %), aqueously altered
      carbonaceous chondrite and contains high concentrations of presolar grains and
      carbonate minerals, which is consistent with the expectation that the D-type
      asteroids were originally made of primitive materials and did not experience any
      extensive heating.

PMID- 11520951
TI  - On the dynamic origins of allosteric activation.

PMID- 11520952
TI  - Human embryo research: lessons from history.

PMID- 11520953
TI  - The Gulf War's aftermath: Kuwait unveils plan to treat festering desert wound.

PMID- 11520954
TI  - Cosmology. Changing constants cause controversy.

PMID- 11520956
TI  - Materials science. Silicon lights the way to faster data flow.

PMID- 11520955
TI  - Scientific misconduct. Wellcome rules widen the net.

PMID- 11520957
TI  - Ecology. African elephant species splits in two.

PMID- 11520958
TI  - Virology. Finally, a handle on the hantaviruses.

PMID- 11520959
TI  - Animal care. Coulston loses NIH tie, faces hard times.

PMID- 11520960
TI  - Canada. Scientists want tougher endangered species law.

PMID- 11520962
TI  - Neuroscience. Nearby rival takes quieter course.

PMID- 11520961
TI  - Neuroscience. New brain institute struggles for traction.

PMID- 11520963
TI  - Neuroscience. Sharp edges into new terrain. Interview by Andrew Lawler.

PMID- 11520964
TI  - DNA forensics. Laying ghosts to rest in Bosnia.

PMID- 11520965
TI  - Astronomy. India seeks partners for 'Himalayan space telescope'.

PMID- 11520966
TI  - Ecological Society of America. Forests: no greenhouse antidote?

PMID- 11520967
TI  - Ecological Society of America. Breeding a hardier weed.

PMID- 11520968
TI  - Ecological Society of America. Case of the missing mammals.

PMID- 11520969
TI  - Infectious disease. Medical helminthology in the 21st century.

PMID- 11520970
TI  - Energy. Exploiting wind versus coal.

PMID- 11520971
TI  - Plant biology. Pollen tube guidance--right on target.

PMID- 11520972
TI  - Earthquakes. Himalayan seismic hazard.

PMID- 11520973
TI  - Bioremediation. Anaerobes to the rescue.

PMID- 11520974
TI  - Biomedicine. Tauists and beta-aptists united--well almost!

PMID- 11520975
TI  - Cell biology. Caveolae--not just craters in the cellular landscape.

PMID- 11520976
TI  - A portrait of Alzheimer secretases--new features and familiar faces.
AB  - The amyloid beta-peptide (Abeta) is a principal component of the cerebral plaques
      found in the brains of patients with Alzeheimer's disease (AD). This insoluble 40
      to 42-amino acid peptide is formed by the cleavage of the Abeta precursor
      protein (APP). The three proteases that cleave APP, alpha-, beta-, and gamma
      secretases, have been implicated in the etiology of AD. beta-Secretase is a
      membrane-anchored protein with clear homology to soluble aspartyl proteases, and
      alpha-secretase displays characteristics of certain membrane-tethered
      metalloproteases. gamma-Secretase is apparently an oligomeric complex that
      includes the presenilins, which may be the catalytic component of this protease.
      Identification of the alpha-, beta-, and gamma-secretases provides potential
      targets for designing new drugs to treat AD.

PMID- 11520977
TI  - Highly polarized photoluminescence and photodetection from single indium
      phosphide nanowires.
AB  - We have characterized the fundamental photoluminescence (PL) properties of
      individual, isolated indium phosphide (InP) nanowires to define their potential
      for optoelectronics. Polarization-sensitive measurements reveal a striking
      anisotropy in the PL intensity recorded parallel and perpendicular to the long
      axis of a nanowire. The order-of-magnitude polarization anisotropy was
      quantitatively explained in terms of the large dielectric contrast between these
      free-standing nanowires and surrounding environment, as opposed to quantum
      confinement effects. This intrinsic anisotropy was used to create polarization
      sensitive nanoscale photodetectors that may prove useful in integrated photonic
      circuits, optical switches and interconnects, near-field imaging, and high
      resolution detectors.

PMID- 11520978
TI  - Time-resolved measurement of dissipation-induced decoherence in a Josephson
      junction.
AB  - We determined the dissipation-induced decoherence time (DIDT) of a
      superconducting Josephson tunnel junction by time-resolved measurements of its
      escape dynamics. Double-exponential behavior of the time-dependent escape
      probability was observed, suggesting the occurrence of a two-level decay
      tunneling process in which energy relaxation from the excited to the ground level
      significantly affects the escape dynamics of the system. The observation of
      temporal double-exponential dependence enables direct measurements of the DIDT, a
      property critical to the study of quantum dynamics and the realization of
      macroscopic quantum coherence and quantum computing. We found that the DIDT was
      tau(d) > 11 micros at T = 0.55 K, demonstrating good prospects for implementing
      quantum computing with Josephson devices.

PMID- 11520979
TI  - Water-induced fabric transitions in olivine.
AB  - The interpretation of seismic anisotropy in Earth's upper mantle has
      traditionally been based on the fabrics (lattice-preferred orientation) of
      relatively water-poor olivine. Here we show that when a large amount of water is
      added to olivine, the relation between flow geometry and seismic anisotropy
      undergoes marked changes. Some of the puzzling observations of seismic anisotropy
      in the upper mantle, including the anomalous anisotropy in the central Pacific
      and the complicated anisotropy in subduction zones, can be attributed to the
      enrichment of water in these regions.

PMID- 11520980
TI  - Repeating deep earthquakes: evidence for fault reactivation at great depth.
AB  - We have identified three groups of deep earthquakes showing nearly identical
      waveforms in the Tonga slab. Relocation with a cross-correlation method shows
      that each cluster is composed of 10 to 30 earthquakes along a plane 10 to 30
      kilometers in length. Some of the earthquakes are colocated, demonstrating
      repeated rupture of the same fault, and one pair of events shows identical
      rupture complexity, suggesting that the temporal and spatial rupture pattern was
      repeated. Recurrence intervals show an inverse time distribution, indicating a
      strong temporal control over fault reactivation. Runaway thermal shear
      instabilities may explain temporally clustered earthquakes with similar waveforms
      located along slip zones weakened by shear heating. Earthquake doublets that
      occur within a few hours are consistent with events recurring before the thermal
      energy of the initial rupture can diffuse away.

PMID- 11520981
TI  - An ultradense polymorph of rutile with seven-coordinated titanium from the Ries
      crater.
AB  - We report the discovery of an ultradense post-rutile polymorph of titanium
      dioxide in shocked gneisses of the Ries crater in Germany. The microscopic
      diagnostic feature is intense blue internal reflections in crossed polarizers in
      reflected light. X-ray diffraction studies revealed a monoclinic lattice,
      isostructural with the baddeleyite ZrO2 polymorph, and the titanium cation is
      coordinated with seven oxygen anions. The cell parameters are as follows: a =
      4.606(2) angstroms, b = 4.986(3) angstroms, c = 4.933(3) angstroms, beta (angle
      between c and a axes) = 99.17(6) degrees; space group P2(1)/c; density = 4.72
      grams per cubic centimeter, where the numbers in parentheses are standard
      deviations in the last significant digits. This phase is 11% denser than rutile.
      The mineral is sensitive to x-ray irradiation and tends to invert to rutile. The
      presence of baddeleyite-type TiO2 in the shocked rocks indicates that the peak
      shock pressure was between 16 and 20 gigapascals, and the post-shock temperature
      was much lower than 500 degrees C.

PMID- 11520982
TI  - Large groundwater strontium flux to the oceans from the Bengal Basin and the
      marine strontium isotope record.
AB  - Strontium concentration and isotopic data for subsurface flowing groundwaters of
      the Ganges-Brahmaputra (G-B) delta in the Bengal Basin demonstrate that this is a
      potentially significant source of strontium to the oceans, equal in magnitude to
      the dissolved strontium concentration carried to the oceans by the G-B river
      waters. The strontium concentrations of groundwaters are higher by a factor of
      about 10 than typical G-B river waters and they have similar 87Sr/86Sr ratio to
      the river waters. These new data suggest that the present contribution of the G-B
      system to the rise in 87Sr/86Sr ratio in seawater is higher by at least a factor
      of 2 to 5 than the average over the past 40 million years.

PMID- 11520983
TI  - Genetic evidence for two species of elephant in Africa.
AB  - Elephants from the tropical forests of Africa are morphologically distinct from
      savannah or bush elephants. Dart-biopsy samples from 195 free-ranging African
      elephants in 21 populations were examined for DNA sequence variation in four
      nuclear genes (1732 base pairs). Phylogenetic distinctions between African forest
      elephant and savannah elephant populations corresponded to 58% of the difference
      in the same genes between elephant genera Loxodonta (African) and Elephas
      (Asian). Large genetic distance, multiple genetically fixed nucleotide site
      differences, morphological and habitat distinctions, and extremely limited
      hybridization of gene flow between forest and savannah elephants support the
      recognition and conservation management of two African species: Loxodonta
      africana and Loxodonta cyclotis.

PMID- 11520984
TI  - The ground state of the ventral appendage in Drosophila.
AB  - In Drosophila melanogaster, the antennae, legs, genitalia, and analia make up a
      serially homologous set of ventral appendages that depend on different selector
      genes for their unique identities. The diversity among these structures implies
      that there is a common ground state that selector genes modify to generate these
      different appendage morphologies. Here we show that the ventral appendage that
      forms in the absence of selector gene activity is leglike but consists of only
      two segments along its proximo-distal axis: a proximal segment and a distal
      tarsus. These results raise the possibility that, during evolution, leglike
      appendages could have developed without selector gene activity.

PMID- 11520985
TI  - Pollen tube attraction by the synergid cell.
AB  - In flowering plants, guidance of the pollen tube to the embryo sac (the haploid
      female gametophyte) is critical for successful fertilization. The target embryo
      sac may attract the pollen tube as the final step of guidance in the pistil. We
      show by laser cell ablation that two synergid cells adjacent to the egg cell
      attract the pollen tube. A single synergid cell was sufficient to generate an
      attraction signal, and two cells enhanced it. After fertilization, the embryo sac
      no longer attracts the pollen tube, despite the persistence of one synergid cell.
      This cessation of attraction might be involved in blocking polyspermy.

PMID- 11520986
TI  - Selective cleavage of D-Ala-D-Lac by small molecules: re-sensitizing resistant
      bacteria to vancomycin.
AB  - Pathogenic enterococci are becoming resistant to currently available antibiotics,
      including vancomycin, the drug of last resort for Gram-positive infections.
      Enterococci pose a significant public health threat, not least because of the
      risk of transferring vancomycin resistance to the ubiquitous Staphylococcus
      aureus. Vancomycin resistance is manifested by cell wall peptidoglycan precursors
      with altered termini that cannot bind the antibiotic. Small molecules with well
      oriented nucleophile-electrophile assembly and complementary chirality to the
      peptidoglycan termini were identified as catalytic and selective cleavers of the
      peptidoglycan precursor depsipeptide. These molecules were tested in combination
      with vancomycin and were found to re-sensitize vancomycin-resistant bacteria to
      the antibiotic.

PMID- 11520987
TI  - Enhanced neurofibrillary degeneration in transgenic mice expressing mutant tau
      and APP.
AB  - JNPL3 transgenic mice expressing a mutant tau protein, which develop
      neurofibrillary tangles and progressive motor disturbance, were crossed with
      Tg2576 transgenic mice expressing mutant beta-amyloid precursor protein (APP),
      thus modulating the APP-Abeta (beta-amyloid peptide) environment. The resulting
      double mutant (tau/APP) progeny and the Tg2576 parental strain developed Abeta
      deposits at the same age; however, relative to JNPL3 mice, the double mutants
      exhibited neurofibrillary tangle pathology that was substantially enhanced in the
      limbic system and olfactory cortex. These results indicate that either APP or
      Abeta influences the formation of neurofibrillary tangles. The interaction
      between Abeta and tau pathologies in these mice supports the hypothesis that a
      similar interaction occurs in Alzheimer's disease.

PMID- 11520988
TI  - Formation of neurofibrillary tangles in P301l tau transgenic mice induced by
      Abeta 42 fibrils.
AB  - beta-Amyloid plaques and neurofibrillary tangles (NFTs) are the defining
      neuropathological hallmarks of Alzheimer's disease, but their pathophysiological
      relation is unclear. Injection of beta-amyloid Abeta42 fibrils into the brains of
      P301L mutant tau transgenic mice caused fivefold increases in the numbers of NFTs
      in cell bodies within the amygdala from where neurons project to the injection
      sites. Gallyas silver impregnation identified NFTs that contained tau
      phosphorylated at serine 212/threonine 214 and serine 422. NFTs were composed of
      twisted filaments and occurred in 6-month-old mice as early as 18 days after
      Abeta42 injections. Our data support the hypothesis that Abeta42 fibrils can
      accelerate NFT formation in vivo.

PMID- 11520989
TI  - Activation by IKKalpha of a second, evolutionary conserved, NF-kappa B signaling
      pathway.
AB  - In mammals, the canonical nuclear factor kappaB (NF-kappaB) signaling pathway
      activated in response to infections is based on degradation of IkappaB
      inhibitors. This pathway depends on the IkappaB kinase (IKK), which contains two
      catalytic subunits, IKKalpha and IKKbeta. IKKbeta is essential for inducible
      IkappaB phosphorylation and degradation, whereas IKKalpha is not. Here we show
      that IKKalpha is required for B cell maturation, formation of secondary lymphoid
      organs, increased expression of certain NF-kappaB target genes, and processing of
      the NF-kappaB2 (p100) precursor. IKKalpha preferentially phosphorylates NF
      kappaB2, and this activity requires its phosphorylation by upstream kinases, one
      of which may be NF-kappaB-inducing kinase (NIK). IKKalpha is therefore a pivotal
      component of a second NF-kappaB activation pathway based on regulated NF-kappaB2
      processing rather than IkappaB degradation.

PMID- 11520990
TI  - Selective transcription and modulation of resting T cell activity by
      preintegrated HIV DNA.
AB  - The quiescent nature of most peripheral T cells poses an effective limitation to
      human immunodeficiency virus (HIV) replication and, in particular, to viral
      integration into the host chromatin. Two HIV proteins, Nef and Tat, increase T
      cell activity, but a requirement of integration for viral gene expression would
      preclude a role for these proteins in resting cells. Here, we report that HIV
      infection leads to selective transcription of the nef and tat genes before
      integration. This preintegration transcription in quiescent cells leads to
      increased T cell activation and viral replication.

PMID- 11520991
TI  - Representation of perceived object shape by the human lateral occipital complex.
AB  - The human lateral occipital complex (LOC) has been implicated in object
      recognition, but it is unknown whether this region represents low-level image
      features or perceived object shape. We used an event-related functional magnetic
      resonance imaging adaptation paradigm in which the response to pairs of
      successively presented stimuli is lower when they are identical than when they
      are different. Adaptation across a change between the two stimuli in a pair
      provides evidence for a common neural representation invariant to that change. We
      found adaptation in the LOC when perceived shape was identical but contours
      differed, but not when contours were identical but perceived shape differed.
      These data indicate that the LOC represents not simple image features, but rather
      higher level shape information.

PMID- 11520992
TI  - Wheezing and the management algorithms for pneumonia in developing countries.

PMID- 11520993
TI  - Improving antibiotic and bronchodilator prescription in children presenting with
      difficult breathing: experience from an urban hospital in India.
AB  - OBJECTIVE: To evaluate the relative frequency of other conditions that share a
      clinical overlap with pneumonia as defined by the WHO case management algorithm
      and to determine the possibility of refining the antibiotic and bronchodilator
      prescription on the basis of simple clinical features. DESIGN: Prospective
      observational. SETTING: Urban tertiary care center. METHODS: Two hundred
      children, between the ages of 6 months to 5 years, presenting with difficult
      breathing (as defined by WHO algorithm) were prospectively evaluated for the
      diagnosis and the need for bronchodilator and antibiotic therapy (clinician s
      diagnosis). An additional independent blinded evaluation of the chest X-rays was
      done by a radiologist after the study (radiologist-aided diagnosis). On the basis
      of reliable predictors (sensitivity > 70% and specificity > 70%) of antibiotic
      and bronchodilator prescription, irrespective of the exact diagnostic category,
      two viable modifications of WHO case management algorithm emerged, which were
      compared by paired proportion test. RESULTS: Acute asthma was the predominant
      condition (46% or 54%), pneumonia alone was rare (10%), co-existence of pneumonia
      with wheeze (bronchospasm) was more frequent (22% or 15%) and often diagnoses not
      related to the respiratory system were documented (18% or 17%). All the subjects
      in whom a preceding history of cough was not elicited had non-respiratory
      illnesses. An audible wheeze was appreciated in only 44 of the 150 cases (29.3%)
      with an auscultable wheeze. The two alternatives represented a significant (p <
      0.0001) improvement over the WHO algorithm preventing inappropriate usage of both
      antibiotics and bronchodilators, primarily by restricting over-prescription of
      the former (14% and 26.5% for proposed algorithms 1 and 2, respectively) and
      under-utilization of the latter (40%). The performance of the alternative
      algorithms for the radiologist-aided diagnosis was marginally better for over
      prescription of antibiotics (16.2% and 30.9% for proposed algorithms 1 and 2,
      respectively). CONCLUSION: It is feasible to amalgamate simple clinical features
      (history of: (i) previous similar episode of cough and difficult breathing, and
      (ii) fever) in the WHO case management algorithm to significantly refine the
      antibiotic (95% CI range 7% to 33%) and bronchodilator (35%; 95% CI 27% to 43%)
      prescription.

PMID- 11520994
TI  - Feeding problems in children with cerebral palsy.
AB  - OBJECTIVE: To determine the magnitude and extent of feeding problems in children
      with cerebral palsy (CP) and to evaluate the effectiveness of nutritional
      interventions. DESIGN: Prospective hospital based interventional study. METHOD:
      Children with cerebral palsy of either sex were enrolled randomly and their
      parents were interviewed for their perception about feeding problems, nutritional
      status and for their views about the expected outcome of feeding problems. Each
      case was assessed for feeding problems based on Gisel and Patrick feeding skill
      score; for nutritional status by measurement of weight, skinfold thickness (at
      biceps, triceps, suprailiac and subscapular), mid arm circumference and caloric
      intake; neurologically for type and severity of cerebral palsy and for
      developmental age by Gasell s developmental scale. Equal number of age and sex
      matched controls were included for comparison of nutritional status and
      developmental quotient. Various rehabilitation procedures were applied and their
      response was observed in the followup ranging from 3-10 months. RESULTS: One
      hundred children (76 boys and 24 girls) with cerebral palsy of mean age 2.5 years
      (range 1 to 9 years) and mean developmental age of 7.6 months (range 1 to 36
      months) were included in the study. Oral motor dysfunction (OMD) was found in all
      cases and in each category. Spastic quadriplegic cerebral palsy (SQCP) and
      hypotonic patients had significantly poor feeding skill score (p < 0.001). Mean
      duration of feeding session was 31.5 minutes (range 10-60 minutes). Main food of
      children with cerebral palsy consisted of liquid and semisolid diet. Children
      with poor OMD were unable to take solid food. Cases with seizures had
      significantly more feeding problems than those without seizures (p < 0.001).
      Parental awareness about feeding problems of their children was significantly low
      and they overestimated the nutritional status of their children. Anthropometric
      indicators were significantly lower than controls (p < 0.001). Spastic
      quadreparesis, hypotonia and poor feeding skill score had negative effect on
      nutritional status. Thirty per cent parents of cerebral palsy patients were
      pessimistic about the possibility of any improvement in feeding problems. After
      nutritional rehabilitation, good improvement was seen in feeding problems, OMD
      and nutritional status. CONCLUSION: Nutritional status of children with cerebral
      palsy is poor due to summation of several factors. Therefore, they should be
      thoroughly assessed for feeding problems and nutritional status in order to start
      timely nutritional rehabilitation which can significantly improve their
      nutritional status and quality of life.

PMID- 11520995
TI  - IAP guidelines for postgraduate medical education in pediatrics. Indian Academy
      of Pediatrics.

PMID- 11520996
TI  - Management of hypogammaglobulinemia.

PMID- 11520997
TI  - PALS guidelines 2000.

PMID- 11520998
TI  - Proteomics: challenge for the new millennium.

PMID- 11520999
TI  - The information highway: a threat to medical confidentiality.

PMID- 11521000
TI  - Use of percutaneous silastic central venous catheters in the management of
      newborn infants.

PMID- 11521001
TI  - Evaluation of cholestatic jaundice in young infants.

PMID- 11521002
TI  - Transient neonatal hyperglycemia.

PMID- 11521003
TI  - Comparison of urinary iodine excretion and goiter survey to determine the
      prevalence of iodine deficiency.

PMID- 11521004
TI  - Lactobacillus casei in the control of acute diarrhea--a pilot study.

PMID- 11521005
TI  - Cyclosporine pharmacokinetics in a renal allograft recipient.

PMID- 11521006
TI  - Hyperornithinemia associated with gyrate atrophy of the choroid and retina in a
      child with myopia.

PMID- 11521007
TI  - Carbohydrate-deficient glycoprotein syndrome (CDGS) 1a.

PMID- 11521008
TI  - Lipemia retinalis.

PMID- 11521009
TI  - Sideroblastic anemia.

PMID- 11521010
TI  - Tetanus immunization in injured individuals.

PMID- 11521012
TI  - Sion Hospital formulae for management of hypoglycemia.

PMID- 11521013
TI  - Steroid induced pica?

PMID- 11521014
TI  - Rusty-pipe syndrome.

PMID- 11521015
TI  - Standardization of Mantoux test.

PMID- 11521016
TI  - Colorectal carcinoma in children in developing countries.

PMID- 11521017
TI  - Calf circumference for identification of low birth weight babies.

PMID- 11521018
TI  - Children's orthopaedics in underdeveloped regions: making it better.

PMID- 11521019
TI  - Three weeks of Kirschner wire fixation for displaced lateral condylar fractures
      of the humerus in children.
AB  - The authors assessed whether a period of 3 weeks, rather than the commonly used 6
      weeks, of smooth Kirschner wire fixation and cast immobilization of the elbow was
      sufficient to achieve union of displaced fractures of the lateral humeral condyle
      treated by open reduction. The authors found only one nonunion in a case series
      of 104 children treated with 3 weeks of fixation. Infections occurred in two
      children (2%). Late review of 63 children (61%) showed abnormalities of elbow
      shape in 28 (44%) and wide surgical scars in 43 (68%). The abnormalities of elbow
      shape were mainly due to overgrowth of the lateral humeral condyle, to the
      formation of excessive amounts of bone over the outer surface of the condyle, or
      both. The authors' findings indicate that a period of 3 weeks of smooth Kirschner
      wire fixation and elbow immobilization is sufficient to achieve healing in most
      displaced fractures of the lateral humeral condyle treated by open reduction. The
      findings also indicate that new strategies are needed to reduce the occurrence of
      overgrowth of the lateral condyle, excessive formation of bone over the condyle,
      and wide scars.

PMID- 11521020
TI  - Radial neck fracture nonunion in children.
AB  - Radial neck nonunion in children is a rare complication of a displaced radial
      neck fracture. The authors conducted a retrospective review of nine cases of
      radial neck nonunion in an effort to identify risk factors for nonunion and to
      evaluate treatment options. Nine patients, average age 8.2 years, sustained
      displaced Salter-Harris type II fractures of the radial neck, with average
      angulation of 83 degrees and average displacement of 83%, and elbow dislocation
      or additional fracture in eight of nine patients. Initial treatment with open
      reduction achieved anatomical alignment of the fracture fragments in seven of the
      nine patients. Initial reduction was lost and radial neck nonunion developed in
      all patients. The nonunion was treated with observation, radial head and neck
      excision, or open reduction and internal fixation with bone graft, depending on
      the level of pain, deformity, and functional deficit. Healing of the nonunion did
      not necessarily lead to improvement of clinical symptoms. Severity of initial
      fracture displacement and inadequate fixation technique contributed to radial
      neck nonunion. Treatment of the nonunion should depend on the patient's pain,
      deformity, and functional restriction.

PMID- 11521021
TI  - Evaluation of the late neurologic deficits accompanied by hypertrophic scars and
      keloids in children with elbow fractures.
AB  - In this study, the relation between hypertrophic scar and keloid (HSc) lesions
      around incisions and late neurologic deficits was investigated in operated elbow
      fractures in children. Six elbow fracture patients with HSc lesions were
      evaluated for neurologic deficits with late onset. The fractures were all closed
      and treated with open reduction and internal fixation. No neurologic deficit was
      detected before surgery and in the early postoperative periods. Late neurologic
      deficits observed in these patients were evaluated according to British Medical
      Research Committee scoring scale on admission and after therapy. In the
      reoperations for neurologic deficits, the nerve segments were found to be
      compressed in intensive scar tissue. Typical pseudoneuromas were observed in the
      proximal part of compression; however, the corporal integrity of the nerves was
      not interrupted. External neurolysis were performed in all patients. Excellent
      improvements in sensory and motor functions were detected and no recurrence
      occurred in follow-up. Elbow fracture patients, especially those with HSc lesions
      around their incisions, should be followed up for possible neurologic deficits
      with late onset.

PMID- 11521022
TI  - Surgical treatment of posttraumatic elbow contracture in adolescents.
AB  - Thirteen adolescent patients with posttraumatic elbow contractures were treated
      with open surgical release at an average of 16.2 years of age. When possible, an
      extensile medial approach to the elbow was used. All patients were treated with 6
      weeks of postoperative continuous passive motion in addition to physical therapy
      and splinting. Eleven patients with >6 months of follow-up were evaluated at an
      average of 29 months after surgery. Average loss of extension improved from 57
      degrees to 15 degrees, and average flexion improved from 109 degrees to 123
      degrees. Average total arc of motion improved from 53 degrees to 107 degrees.
      Complications included one case of wound drainage requiring irrigation and
      debridement and one case of transient ulnar neuropraxia. One of the 13 patients
      was unable to tolerate postoperative therapy and showed loss of motion.

PMID- 11521023
TI  - Pediatric traumatic atlanto-occipital dislocation: five cases and a review.
AB  - Traumatic atlanto-occipital dislocation (AOD) has been thought to be a rare and
      fatal injury. Recently, more survivors, especially children, have been reported.
      During a 10-year period, the authors have encountered five children with
      traumatic AOD. A retrospective review of traumatic AOD in children from 1985 to
      1995 was performed. Clinical presentation, initial radiologic findings, and final
      outcome were emphasized. Distance from the dens to the basion and the ratio of
      Powers were measured from initial lateral cervical spine radiographs. The average
      distance from the dens to the basion was 9.8 mm. The average ratio of Powers was
      1.38. There were three survivors, two having a concomitant spinal cord injury.
      All survivors underwent a posterior occipitovertebral fusion. Three cases
      initially went undiagnosed. The diagnosis of AOD by lateral cervical spine
      radiographs can be difficult. The authors recommend detailed measurements of the
      initial cervical spine radiographs in pediatric patients at risk for traumatic
      AOD.

PMID- 11521024
TI  - Unusual upper cervical fracture in a 1-year-old girl.
AB  - Injuries to the child's cervical spine are rare and, unlike adults, most common
      from the occiput to C3. Most odontoid fractures in children occur through the
      basilar synchondrosis and only the dens is displaced anteriorly. The authors
      report the clinical and radiologic evaluation of a child who sustained an unusual
      cervical injury during a motor vehicle accident. The lesion consisted of an
      epiphyseal fracture-separation between the body and the neural arches of C2.
      There was also an associated spinal cord lesion.

PMID- 11521026
TI  - Supracondylar fractures of the femur in children.
AB  - Nonphyseal supracondylar fractures of the femur are considered to be uncommon in
      children and have received little attention in the literature. A retrospective
      review of femoral fractures in children at the authors' institution was
      undertaken to ascertain the incidence of supracondylar femoral fractures, the
      influence of associated musculoskeletal conditions, and pitfalls of management.
      In this study of 102 femoral fractures, there was an incidence of 12% of
      supracondylar fractures. Four of 12 patients had a significant predisposing
      musculoskeletal condition contributing to the genesis of the fracture. Five
      fractures were undisplaced and easily managed. Seven displaced fractures required
      intervention to achieve an adequate reduction. The literature is reviewed and a
      classification system for these fractures is presented. Treatment options are
      discussed and recommendations made based on this experience.

PMID- 11521025
TI  - Early versus late femoral fracture stabilization in multiply injured pediatric
      patients with closed head injury.
AB  - The purpose of this study was to analyze retrospectively pediatric femur fracture
      patients with concomitant head injury to determine whether time to fracture
      fixation affects central nervous system, orthopaedic, or additional
      complications. Twenty-five patients with a Head Abbreviated Injury Scale score of
      > or =3 and a femoral shaft fracture were reviewed. Patients were divided by time
      to treatment for their femur fracture. Average stay was 10.5 days for the early
      group and 18.5 days for the late group, the only statistically significant
      finding. Orthopaedic and central nervous system complications were similar
      between the two groups. Sixteen additional complications were found in the late
      group versus three for the early group. Femur fractures in the head-injured
      pediatric patient can be adequately addressed with early or late fixation with
      similar long-term outcomes. Early femur fracture fixation may decrease the length
      of hospital stay and the number of nonorthopaedic, nonneurologic complications.

PMID- 11521027
TI  - Ultrasound examination of ankle injuries in children.
AB  - Fourteen children with ankle injuries, an open tibia and fibula physis, and
      negative radiographs had ultrasonography of their injured ankles. Five had an
      anterior talofibular ligament injury and five had an anterior tibiofibular
      ligament injury. Four had normal ultrasound examinations. Only two had a physeal
      injury, both of which were associated with a ligament injury. Eleven children had
      only lateral ankle tenderness. Ultrasound of these 11 revealed ligamentous
      injuries, normal examinations, and the two physeal injuries. Ligamentous injury
      was not associated with other tenderness patterns.

PMID- 11521028
TI  - Physeal injury in a lightning strike survivor.
AB  - Electrical injuries resulting in physeal injury in children are an uncommon but
      well-recognized clinical entity. Almost all these injuries are sustained from man
      made electrical sources. To date, there have been no published cases of growth
      arrest after lightning strike. The authors report the case of a 12-year-old girl
      who survived a lightning strike 2 years ago and who presented with asymmetric
      growth arrest in both legs. The authors discuss the pathophysiology of lightning
      strike and consider the evidence for direct electrical injury versus ischemic
      insult to the physis as explanations for the cause of the growth arrest observed
      in this patient.

PMID- 11521029
TI  - In-line skating injuries in children: a 10-year review.
AB  - In-line skating is an increasingly popular recreational activity for both
      children and adults. As with any high-speed sport, traumatic injury is an
      associated hazard. It was the purpose of this study to focus on the injuries in
      children associated specifically with in-line skating with an emphasis on
      education and prevention. During a 9-year period, 331 injuries were identified,
      with 105 families completing an in-depth epidemiologic questionnaire. Sixty-one
      percent of the victims were boys, with an overall average age of 12 years. The
      upper extremity was most commonly injured (64%); the head and neck area was
      injured in 16% and the lower extremity in 20%. Fractures represented 38% of all
      injuries, with inexperience appearing to be the most common cause. An analysis of
      preventive strategies for childhood in-line skating was undertaken using Haddon's
      10 basic preventive principles. Educational programs regarding instruction in in
      line skating and the value of protective equipment need to be part of the school
      curriculum.

PMID- 11521030
TI  - The Pediatric Orthopaedic Society of North America pediatric orthopaedic
      functional health questionnaire: an analysis of normals.
AB  - Several questionnaires have been developed in an attempt to measure real-life
      functional levels of pediatric orthopaedic patients. One in particular was
      developed by the Pediatric Orthopaedic Society of North America (POSNA) in 1994.
      This POSNA instrument yields four functional assessment scores, a global function
      score, and a happiness score (each having a possible range from 0 to 100). In
      this study, the POSNA questionnaire was administered to the parents of 57 normal
      children and 27 normal adolescents to determine how normal respondents can be
      expected to score. Means, standard deviations, and other statistics were derived
      for the functional scores. It was concluded that normal children should respond
      quite high on all the scores, possibly 100. These results allow us to understand
      that a child scoring in the low 80s or less is functioning at a different level
      than the normal child.

PMID- 11521031
TI  - Assessment of quality of life in adolescent patients with orthopaedic problems:
      are adult measures appropriate?
AB  - New pressures of accountability brought on by a rapidly evolving system of health
      care financing have underscored the need for standardized, valid measures of
      patient outcome that reflect the effect of clinical intervention on all aspects
      of quality of life. In response, there has been a burgeoning interest in the area
      of outcomes assessment and measurement of quality of life after orthopaedic
      intervention in adults, but less attention has been focused on the assessment of
      broadly defined outcomes in children. In an effort to borrow from the broader
      adult experience in this area, the authors sought to examine whether the Medical
      Outcomes Study Short Form 36 (SF-36) or the EuroQol questionnaire, widely
      accepted adult health status measures, would be valid in this setting. These two
      measures were administered to 196 adolescent patients (10-18 years old) seeking
      orthopaedic evaluation. Tests of scale properties and construct validity show
      that these properties are maintained in this population, but neither instrument
      reflected known differences in health status among this cohort. Most importantly,
      both the SF-36 and the EuroQol exhibited serious ceiling effects (most
      respondents scored at the top of their scales), despite evidence indicating those
      patients often had suboptimal health status. Thus, neither the SF-36 nor the
      EuroQol is valid for use in this population. The assessment of pediatric health
      status demands outcomes measures specifically designed to reflect the unique
      needs of this population.

PMID- 11521032
TI  - Capturing quality of life in pediatric orthopaedics: two recent measures
      compared.
AB  - There is a clear need for standardized measures to assess health status that are
      valid and appropriate to the needs of children with orthopaedic problems. The
      Child Health Questionnaire and the American Academy of Orthopaedic Surgeons
      Pediatric Outcomes Data Collection Instrument, two new pediatric health status
      measures, were assessed for their ability to detect differences in health states
      in a pediatric orthopaedic population. The instruments have a range of scales
      designed to measure various aspects of physical and psychosocial health. Two
      hundred forty-two patients with wide-ranging diagnoses were enrolled in this
      cross-sectional study. The instruments exhibited ceiling effects in some domains
      but generally performed as they were intended in this large cohort. Using
      secondary factor analysis, it was shown that the domains of the instruments
      appropriately distinguish physical and psychosocial health. Several domains from
      each instrument discriminated between diagnosis groups and patients with varying
      numbers of comorbidities. Both of these measures show significant promise and
      have an important role in helping define the outcomes of children with
      orthopaedic problems.

PMID- 11521033
TI  - Review of the effect of early amniocentesis on foot deformity in the neonate.
AB  - A recent publication by the Canadian Early and Mid-Trimester Amniocentesis Trial
      Group reported an increase in orthopaedic foot deformities in infants whose
      mothers underwent an amniocentesis from 11 to 12 + 6 gestational weeks versus a
      group sampled between 15 to 16 + 6 gestational weeks. Because the sampling of the
      former group was at the time of maximum foot growth and maximum acquisition of
      amniotic fluid, the authors hypothesize that the foot deformities are secondary
      to decreased fetal movement during a key phase in foot and ankle development.

PMID- 11521034
TI  - Evaluation of the treatment of clubfeet with the Dimeglio score.
AB  - Between January 1994 and November 1997, 17 children with 25 clubfeet were treated
      and evaluated. This group was divided into a group of only conservatively treated
      feet (group A, n=13) and a group of feet which had conservative treatment and
      complementary operative treatment (group B, n=12). Both groups were evaluated
      according to the Dimeglio classification method in which the objective clinical
      evaluation is scored only. This was performed for the starting-point (at
      presentation until 2 weeks after birth), with the necessary information received
      from the patient's files where all the passive limitations were recorded in a
      standardized way and also for the end-point (at the time of the follow-up). After
      comparing these results to each other, all 25 feet had improved after treatment
      and the operative group had improved more than the conservative group, however
      the end result was equal, because the operated feet were more severely deformed
      before the treatment. After treatment, the results were considered acceptable in
      92% of the feet, comparable to 93%, 75-85%, 88%, 77%, and 96% in other studies.
      Moreover, the forefoot adduction was the most common residual sign in the treated
      feet, confirmed by results in other studies. We conclude that the Dimeglio method
      is an appropriate tool for the follow-up of clubfeet from birth to the end of
      treatment.

PMID- 11521035
TI  - A three-dimensional study of calcaneonavicular tarsal coalitions.
AB  - The authors studied 37 presumed calcaneonavicular tarsal coalitions from the
      Hamann-Todd Osteological Collection at the Cleveland Museum of Natural History.
      The anatomy of the coalitions and the associated subtalar and transverse tarsal
      joints was quite variable. The coalitions in 8 specimens completely spared the
      anterior facet of the calcaneus and in 7 specimens it was partially replaced by
      the navicular portion of the coalition, whereas in 22 specimens the anterior
      calcaneal facet was completely replaced by the navicular portion of the
      coalition. The authors suggest that the pathoanatomy of calcaneonavicular
      coalitions is not uniform and may involve the subtalar and transverse tarsal
      joints. This may have clinical relevance and contribute to the unsatisfactory
      results in feet undergoing coalition resection and soft tissue interposition.

PMID- 11521036
TI  - Three-dimensionally corrective external fixator system for proximal femoral
      osteotomy.
AB  - The authors introduce a technique of proximal femoral osteotomy using three
      dimensionally corrective external fixator systems for treatment of Legg-Calve
      Perthes disease and slipped capital femoral epiphysis, and describe the results
      of 47 hips in 44 children. Postoperative casting immobilization was not
      performed. All osteotomies gained the correction angle as planned. All
      osteotomies healed with no nonunions, malunions, device failures, or avascular
      necrosis. Complications occurred in 7 (15%) of 47 hips. Pin tract infection
      occurred in six (13%) hips; one of these (2%) needed debridement. The bulky
      external fixator caused slight inconvenience, but the current results indicate
      that the proximal femoral osteotomy using the external fixator system provided an
      easily repeatable intraoperative varus/valgus and flexion/extension correction
      compared with other internal fixation devices, and sufficient fixation for
      children without significant complications.

PMID- 11521037
TI  - The hip in Stickler syndrome.
AB  - Stickler syndrome is an autosomal dominant connective tissue disorder with a
      prevalence similar to that of Marfan syndrome. No previous study has examined hip
      pain or abnormalities in a large series of patients with Stickler syndrome. The
      purpose of this study was to describe hip abnormalities and their correlation
      with age and chronic hip pain in a cohort of 51 patients followed at the National
      Institutes of Health. Ten percent of patients had protrusio acetabuli, 21% coxa
      valga, and 34% of adults had hip osteoarthritis. Sixty-three percent of all
      patients and 79% of adults had chronic hip pain. In addition, 16% of adult
      patients had a history of femoral head failure during youth. Arthritic changes
      and adult age were associated with hip pain. In summary, hip abnormalities are
      commonly observed in Stickler syndrome. Young patients require careful evaluation
      of hip pain, and regular screening of children with Stickler syndrome may be
      indicated for early detection of hip complications.

PMID- 11521038
TI  - Vascular supply to slipped capital femoral epiphysis.
AB  - The etiology of avascular necrosis associated with slipped capital femoral
      epiphysis has not been well understood. The aims of this study were to clarify
      the blood supply to the slipped epiphysis and to examine whether this vascular
      supply is damaged before the reduction. Twelve patients (12 hips) underwent
      selective angiography of the medial circumflex femoral artery. There were seven
      stable slips and five unstable slips. All patients with slips underwent
      angiography before reduction, and one patient with an unstable slip underwent
      angiography both before and after reduction. The superior retinacular artery
      (SRA) was filled in all stable slips. This result was in accordance with the
      previous report that stable slips result in low rates of avascular necrosis. Of
      five unstable slips, the SRA was stained in two and was not filled in three. In
      one slip examined both before and after the manipulative reduction, the SRA was
      not seen before it but was well stained after it. These results have suggested
      that in some unstable slips the vascular injury occurs at the time of injury,
      before reduction, and that the reduction dose not necessarily contribute to the
      risk of avascular necrosis after slipped capital femoral epiphysis.

PMID- 11521039
TI  - Limited hip abduction in the infant.
AB  - This article addresses two important questions: What is the relationship between
      limited abduction and hip dysplasia in infants? Does untreated limited abduction
      in the infant ultimately lead to developmental dysplasia of the hip? In the
      authors' population of 683 babies, limitation of abduction had a sensitivity for
      the diagnosis of hip dysplasia of 69%, a specificity of 54%, a positive
      predictive value of 43%, and a negative predictive value of 78%. In the group
      with sonographically proven hip dysplasia, 70 of 226 babies (31%) showed no
      limitation of abduction, and in the group without dysplasia 210 of 457 (46%)
      showed manifest limitation of abduction. One hundred thirty-six babies with
      limited abduction but a normal sonographic examination were left untreated. They
      were re-examined at an average age of 5+3 years (range 2+0-9+5). All had
      developed normally, both clinically and radiographically.

PMID- 11521040
TI  - Pediatric tourniquets: analysis of cuff and limb interface, current practice, and
      guidelines for use.
AB  - There are few clear guidelines on the proper use of tourniquets in pediatric
      surgery, in particular on how to set the tourniquet pressure, how to select the
      most appropriate cuff, and whether to use some type of soft padding beneath the
      cuff for limb protection. The authors could find only one published study
      specifically addressing pediatric cuff pressures, and no studies showing what
      types of cuff and/or padding create the smoothest skin surface under the cuff. Of
      46 pediatric orthopaedic surgeons surveyed, 44 use a tourniquet 4.6 times per
      week on average and 2 have discontinued their use as a result of complications.
      To set cuff pressure, 13 of 44 use a standard value, 14 of 44 base pressure on
      age, extremity, and size, and 17 of 44 base cuff pressure on blood pressure.
      Thirty-four of 44 use skin protection under the cuff, but damage to the skin is
      common, accounting for 21 of the 67 reported complications. Nerve (15/67) and
      muscle (8/67) complications, related to both pressure and tourniquet time, were
      also reported. Using a molding and digital measurement technique, the authors
      compared the maximum wrinkle heights and the sums of all wrinkle heights in the
      skin surface under four different cuff/padding configurations. In a total of 44
      trials on the upper arms and thighs of two healthy child volunteers, one type of
      pediatric cuff with a matching limb-protection sleeve designed and recommended by
      the manufacturer (Delfi) produced significantly fewer, less severe pinches and
      wrinkles in the skin surface than a second type of tourniquet cuff (Zimmer) with
      or without two layers of commonly available cast padding, and a third type
      (Kidde) with padding. With the second type of cuff, using cast padding reduced
      skin wrinkling compared to applying the same cuff on unprotected skin. In view of
      the survey, clinical literature, and results of this study, a guideline for use
      of pediatric tourniquets is proposed.

PMID- 11521041
TI  - Prevalence of positive preoperative pregnancy testing in teenagers scheduled for
      orthopedic surgery.
AB  - The pregnancy status of female teenagers presenting for orthopaedic surgery is
      often unknown. Anesthetics may have teratogenic or abortive effects. The authors
      report the results of a screening program for unrecognized pregnancy in 532
      female teenagers presenting for orthopaedic surgery. Five patients with a
      positive urine human chorionic gonadotropin test were identified, for a
      prevalence of 1 positive result in 106 patients tested (0.9%). Surgery was
      cancelled in each case.

PMID- 11521042
TI  - Acute compartment syndrome in children: contemporary diagnosis, treatment, and
      outcome.
AB  - Compartment syndrome can be difficult to diagnose in a child, with delays in
      diagnosis leading to disastrous outcomes. Thirty-six cases of compartment
      syndrome in 33 pediatric patients were treated at the authors' institution from
      January 1, 1992, to December 31, 1997. There were 27 boys and 6 girls, with
      nearly equal upper and lower extremity involvement. Approximately 75% of these
      patients developed compartment syndrome in the setting of fracture. Pain, pallor,
      paresthesia, paralysis, and pulselessness were relatively unreliable signs and
      symptoms of compartment syndrome in these children. An increasing analgesia
      requirement in combination with other clinical signs, however, was a more
      sensitive indicator of compartment syndrome: all 10 patients with access to
      patient-controlled or nurse-administered analgesia during their initial
      evaluation demonstrated an increasing requirement for pain medication. With early
      diagnosis and expeditious treatment, >90% of the patients studied achieved full
      restoration of function.

PMID- 11521043
TI  - Congenital pseudarthrosis of the clavicle: a proposal for early surgical
      treatment.
AB  - We present a review of six cases of children with congenital pseudarthrosis of
      the clavicle, treated and followed up at the "La Fe" Hospital for Children. One
      of them had bilateral involvement. Five of them, including the bilateral case,
      were surgically treated at ages ranging from 18 months to 4 years. Bone graft and
      internal fixation with a Kirschner wire were used. Healing of the pseudarthrosis
      was obtained in all patients in 6-8 weeks. We discuss the suitability of early
      surgical treatment that, in our opinion, produces very satisfactory results.

PMID- 11521044
TI  - Unstable slipped capital femoral epiphysis.

PMID- 11521045
TI  - Preliminary traction in the treatment of developmental dislocation of the hip.

PMID- 11521047
TI  - The search for Lps: 1993-1998.

PMID- 11521048
TI  - Lps: another piece in the puzzle.

PMID- 11521050
TI  - Asystole following endotoxin administration.

PMID- 11521051
TI  - Signaling pathways involved in lipopolysaccharide stimulation of prostaglandin
      production by rat hypothalamic astroglial cells.
AB  - The aim of this study was to investigate the mechanisms through which bacterial
      lipopolysaccharide (LPS) stimulates prostaglandin (PG) production in rat
      hypothalamic astroglial cells in vitro. The latter were treated with LPS alone or
      LPS plus antagonists of the interleukin-1 (IL-1) and nitric oxide (NO) pathways,
      and the subsequent changes in cyclooxygenase (COX) activity were monitored by
      measuring a COX end-product, prostaglandin E2 (PGE2), released into the
      incubation medium. LPS produced a concentration-dependent increase in PGE2
      release from astroglia after 24 h incubation; experiments with selective
      antagonists showed that the increase in PGE2 release induced by LPS may be, at
      least in part, mediated by IL-1 and NO.

PMID- 11521052
TI  - Bacterial endotoxin (lipopolysaccharide) stimulates the rate of iron oxidation.
AB  - Bacterial endotoxin (lipopolysaccharide) has affinity for a number of cations,
      including iron. Previous investigations have demonstrated that lipopolysaccharide
      can affect the oxidation rate of iron; heme-bound ferrous iron in hemoglobin is
      oxidized to ferric iron when hemoglobin binds lipopolysaccharide. In the present
      study, we directly examined the interaction between lipopolysaccharide and iron.
      Lipopolysaccharide caused a concentration-dependent increase in the rate of iron
      oxidation, with up to a 23-fold increase in oxidation in the presence of 200
      microg/ml Escherichia coli lipopolysaccharide. This effect was seen both with
      several carbohydrate-rich smooth lipopolysaccharides and also with carbohydrate
      poor rough lipopolysaccharide. Extensively deacylated rough lipopolysaccharide
      had no effect, suggesting a role of the fatty acid components of
      lipopolysaccharide in this process. Purified lipid A produced inconsistent
      results: some preparations stimulated iron oxidation and others did not. A series
      of sugars, starches and a preparation of purified O-chain polysaccharide (the
      carbohydrate portion of the lipopolysaccharide macro-molecule) had no effect on
      the rate of iron oxidation, whereas phospholipid-enriched brain tissue extracts
      (similar to the lipid A component of lipopolysaccharide) stimulated oxidation. We
      conclude that the lipid moiety of bacterial lipopolysaccharide is responsible for
      the stimulation of iron oxidation. This process may contribute to the ability of
      lipopolysaccharide to cause oxidation of heme-bound iron in hemoglobin.

PMID- 11521053
TI  - Endotoxin tolerance protects against local hepatic ischemia/reperfusion injury in
      the rat.
AB  - Liver surgery and liver transplantation as well as circulatory shock are often
      associated with hepatic ischemia/reperfusion (I/R) injury. Recent evidence
      suggests that TNF-alpha plays a central role in I/R injury and, therefore, down
      regulation of TNF-alpha seems to be a promising way to protect against the
      deleterious consequences of I/R. Endotoxin tolerance represents a state of
      unresponsiveness to endotoxin and is associated with diminished TNF-alpha
      production. Thus, the effect of endotoxin tolerance on hepatic I/R injury of the
      liver was investigated in a rat model. I/R injury was induced by temporary
      ischemia of the left lateral liver lobe for 90 min followed by a 3 h observation
      period of reperfusion. I/R injury resulted in functional hepatic disorder
      characterized by a decrease both in bile flow and bile acid concentration and 50%
      mortality. This was prevented by induction of endotoxin tolerance. Hepatic TNF
      alpha mRNA expression after I/R of the liver was determined by RT-PCR. In
      untreated rats, TNF-alpha mRNA was induced in the liver 60 min after reperfusion
      and further increased until 3 h after reperfusion. In contrast, in endotoxin
      tolerant rats, no increases in TNF-alpha mRNA expression were detected. This
      suggests that induction of endotoxin tolerance protects against hepatic I/R
      injury possibly via down-regulation of intra-organ TNF-alpha expression.

PMID- 11521054
TI  - Induction of TNF-alpha and MnSOD by endotoxin: effect of E5531, a synthetic non
      toxic lipid A analog.
AB  - E5531, a synthetic lipid A analog, has been shown to inhibit endotoxin
      (lipopolysaccharide, LPS)-induced tumor necrosis factor-alpha (TNF-alpha)
      production by human monocytes and murine macrophages. Whether it also inhibits
      LPS induction of manganese superoxide dismutase (MnSOD) is not clear. In the
      current study, we demonstrated that E5531, while having no effect on TNF-alpha
      and MnSOD mRNAs by itself, markedly inhibited LPS- and lipid A-, but not TNF
      alpha-, induced increases in TNF-alpha and MnSOD mRNAs in human monocytes. In
      contrast, E5531 at concentrations and conditions that markedly inhibit LPS
      induced increases in TNF-alpha and MnSOD mRNAs, and TNF-alpha production by human
      monocytes, had no effect on murine peritoneal macrophages. These results
      demonstrate that E5531 is a potent LPS antagonist in human monocytes. However, it
      does not show antagonist action against LPS in murine macrophages in the range of
      concentrations tested, suggesting that E5531 is a more potent antagonist in
      humans than in mice.

PMID- 11521055
TI  - Lipopolysaccharides in the development of the Guillain-Barre syndrome and Miller
      Fisher syndrome forms of acute inflammatory peripheral neuropathies.
AB  - Guillain-Barre syndrome (GBS), an acute inflammatory polyneuropathy, is preceded
      in most cases by an infectious illness, and Campylobacter jejuni, a leading cause
      of acute gastroenteritis, is the most common antecedent to GBS and its ocular
      variant, Miller Fisher syndrome (MFS). O (Penner) serotyping is considered to
      distinguish between C. jejuni strains based on differences in lipopolysaccharide
      (LPS) structure. Serotypes of C. jejuni uncommon in enteritis, such as serotype
      O:19 and O:41, have been associated with GBS. Chemical studies on the core
      oligosaccharide (OS) of C. jejuni LPSs from serotypes including O:1, O:2, O:4,
      O:10, O:19, O:23, O:36 and O:41 have revealed structures that mimic human
      gangliosides including GM1, GD1a, GD2, GD3, and GM2. Research has focused on the
      view that molecular mimicry may be a factor in the pathogenesis of GBS. Serum
      antibodies against gangliosides, particularly GM1 ganglioside, are present in 30%
      of GBS patients, and are highly associated with MFS, but are generally absent in
      enteritis cases uncomplicated by neuropathy. Collective data from human and
      animal studies with anti-ganglioside antibodies suggest a pathogenic role for the
      antibodies. Many aspects of the pathogenesis of GBS are unclear, in particular
      how LPS is presented to T cells or the role of host factors in disease
      development.

PMID- 11521056
TI  - A monoclonal antibody recognizing the 3-deoxy-D-manno-oct-2-ulosonic acid (Kdo)
      trisaccharide alphaKdo(2-->4)alphaKdo(2-->4)alphaKdo of Chlamydophila psittaci
      6BC lipopolysaccharide.
AB  - A monoclonal antibody (mAb) S45-18 was generated against a synthetic
      neoglycoconjugate containing the trisaccharide alphaKdo(2-->4)alphaKdo(2-
      >4)alphaKdo (Kdo, 3-deoxy-D-manno-oct-2-ulopyranosonic acid) which represents a
      structure of the lipopolysaccharide (LPS) from Chlamydophila psittaci 6BC. The
      antibody was characterized by binding and inhibition assays in ELISA using: (i)
      the immunizing antigen and chemically synthesized derivatives thereof; (ii)
      chlamydial elementary bodies (EB); and (iii) LPS of Chl. psittaci 6BC and
      Chlamydia trachomatis L2. The specificity was determined in comparison to that of
      mAb S25-23 recognizing the alphaKdo(2-->8)alphaKdo(2-->4)alphaKdo trisaccharide
      which represents an epitope shared by all species of the family. MAb S45-18 bound
      to an epitope of the structure alphaKdo(2-->4)alphaKdo(2-->4)alphaKdo, with lower
      reactivity with the (2-->8)-(2-->4)-linked analog. Using chlamydial EB or LPS,
      mAb S45-18 bound preferentially to LPS and EB of Chl. psittaci. Therefore, Chl.
      psittaci LPS contains, in addition to the known genus-specific epitope, a species
      specific epitope.

PMID- 11521057
TI  - Phase variation of Coxiella burnetii strain Priscilla: influence of this
      phenomenon on biochemical features of its lipopolysaccharide.
AB  - During the phase variation of Coxiella burnetii, modifications in its
      lipopolysaccharide (LPS) component were investigated. The cloned phase I C.
      burnetii cells were passed serially in chicken embryo yolk sacs up to the egg
      passage (EP) 90. The LPSs from the cells in EPs 3, 12, 21, 40, 60, and 90 were
      all separated by steric exclusion chromatography into three major populations:
      the high, intermediate, and low molecular weight fractions, differing one from
      another in size and chemical composition. No noticeable shortening of the O
      polysaccharide chains was observed in the LPSs isolated during the C. burnetii
      cultivation. However, a redistribution of the existing LPS populations has been
      observed due to an increasing prevalence of those cells in the whole cell
      population that express LPS molecules with truncated O-chains and those being of
      R-type. In the high and intermediate molecular weight LPS populations, virenose
      and dihydrohydroxystreptose are lost gradually with the progress in phase
      variation. This occurs more readily with the former sugar. At present, the
      molecular mechanisms influencing the LPS modifications during the C. burnetii
      phase variation remain unclear.

PMID- 11521058
TI  - Time-dependent effect of LPS on PGE2 and TNF-alpha production by rat glial brain
      culture: influence of COX and cytokine inhibitors.
AB  - This study was undertaken to investigate the effect of lipopolysaccharide (LPS)
      stimulation on the time course of prostaglandin E2 (PGE2) and tumor necrosis
      factor alpha (TNF-alpha) production by rat glial brain culture. A concentration
      of 10 microg/ml LPS from Escherichia coli was used as stimulation treatment. The
      effect of pentoxifylline (PXF), nimesulide (NIM), indomethacin (INDO) and
      dexamethasone (DEX) on the regulation of PGE2 and TNF-alpha production was
      tested. Stimulation of rat glial cells with LPS resulted in different time
      dependent production patterns of PGE2 and TNF-alpha The time course of TNF-alpha
      elevation was short, reaching its peak at 6 h post LPS and decreasing to
      undetectable levels after 24 h. On the other hand, the time course of PGE2
      elevation was longer, starting at 6 h post LPS treatment and increasing 100-fold
      compared with basal levels, 24 h post LPS exposure. The COX inhibitors (NIM and
      INDO) and DEX were found to inhibit the LPS-induced elevation in PGE2 production,
      while PXF lacked such an inhibitory effect. Furthermore, NIM, DEX and PXF were
      found to reduce the LPS-induced elevation in TNF-alpha levels, while INDO caused
      a greater elevation in TNF-alpha levels. These results may cast further light on
      the LPS-induced production of PGE2 and TNF-alpha by rat glial cell cultures and
      the relation between the two systems.

PMID- 11521059
TI  - The role of Toll-like receptors and MyD88 in innate immune responses.
AB  - Toll-like receptors (TLRs) are phylogenetically conserved receptors that
      recognize pathogen associated molecular patterns (PAMPS). We previously generated
      mice lacking TLR2 and TLR4 and showed the differential role of TLR2 and TLR4 in
      microbial recognition. TLR4 functions as the transmembrane component of the
      lipopolysaccharide (LPS) receptor, while TLR2 recognizes peptidoglycan from Gram
      positive bacteria and lipoprotein. We also generated mice lacking MyD88, an
      adaptor involved in IL-1R/TLR signalings. The responses to a variety of bacterial
      components were completely abrogated in MyD88-deficient cells. However, unlike
      the signaling mediated by other bacterial components such as lipoprotein and
      bacterial DNA, activation of NF-kappaB and MAP kinases was induced in response to
      LPS even in the absence of MyD88, which indicates the existence of a MyD88
      independent pathway. We have recently found that the MyD88-independent pathway is
      involved in LPS-induced maturation of dendritic cells (DCs).

PMID- 11521060
TI  - Innate recognition of lipopolysaccharide by Toll-like receptor 4/MD-2 and
      RP105/MD-1.
AB  - The Toll family of receptors has been implicated in innate recognition and
      subsequent activation of defense programs against pathogens such as bacteria and
      fungi. TLR4, for example, signals the presence of lipopolysaccharide (LPS), a
      membrane constituent of Gram-negative bacteria. LPS signaling via TLR4 is greatly
      enhanced by a molecule referred to as MD-2, which is associated with the
      extracellular domain of TLR4. The TLR4/MD-2 complex, therefore, recognizes LPS.
      RP105, another member of the Toll family, has a striking similarity to TLR4 in
      that it is associated with an MD-2-like molecule MD-1. B-cells lacking RP105 are
      severely impaired in LPS-induced proliferation and antibody production. Studies
      employing transfectants showed that RP105/MD-1, like MD-2, enhances the LPS
      signaling via TLR4. RP105/MD-1 thus constitutes an LPS-signaling complex on B
      cells. These results suggest that a variety of cell surface molecules regulate
      LPS recognition/signaling by TLR4.

PMID- 11521061
TI  - Co-operative induction of pro-inflammatory signaling by Toll-like receptors.
AB  - Toll-like receptors (TLRs) mediate detection of a broad range of pathogens and
      pathogen-derived products including LPS, peptidoglycan, bacterial lipopeptides,
      and lipoteichoic acid. Recent evidence indicates that the broad specificity of
      TLRs may be a consequence of the interactions between different TLRs. In this
      report, we demonstrate that while a constitutively active TLR4 homodimer can
      induce the production of pro-inflammatory cytokines, homodimers of TLR2 and TLR6
      cannot. However, when co-expressed in the same cell, constitutively active TLR2
      and TLR6 strongly induce cytokine production, indicating that these TLRs require
      partners to productively signal. Since TLR4 signals as a homodimer, while TLR2
      and TLR6 do not, it is clear that, despite the conservation of their cytoplasmic
      signaling domains, the mechanisms by which they initiate signaling are different.
      We have localized the region of TLR4 that mediates its ability to signal as a
      homodimer to the membrane-proximal half of the cytoplasmic tail of the receptor.

PMID- 11521062
TI  - A horseshoe crab receptor structurally related to Drosophila Toll.
AB  - Innate immunity against microbial pathogens relies on the pattern recognition of
      cell wall components on invading microbes. Recent evidence has shown that a
      mammalian Toll-like receptor (TLR) is activated by bacterial lipopolysaccharides
      (LPS). The innate immunity in invertebrates is also triggered by LPS, as seen in
      the hemolymph coagulation in horseshoe crab. We report the cloning of a TLR from
      the Japanese horseshoe crab Tachypleus tridentatus. A cDNA coding for Tachypleus
      Toll was isolated from a hemocyte cDNA library and the open reading frame codes
      for a proprotein including a signal sequence. Like Drosophila Toll, Tachypleus
      Toll is a type I transmembrane protein with an extracellular domain consisting of
      two leucine-rich repeats flanked by two cystein-rich clusters and a cytoplasmic
      domain exhibiting striking similarity with the cytoplasmic domain of interleukin
      1 receptor. Tachypleus Toll is most similar to Drosophila Toll in the domain
      architecture and the overall length.

PMID- 11521063
TI  - Role of MD-2 in TLR2- and TLR4-mediated recognition of Gram-negative and Gram
      positive bacteria and activation of chemokine genes.
AB  - MD-2 is associated with TLR4 on the cell surface and enables TLR4 to respond to
      LPS. TLR2 without MD-2 does not respond to pure protein-free endotoxic LPS,
      ReLPS, and lipid A. MD-2 enables TLR2 to respond to non-activating LPS, ReLPS,
      and lipid A, and enhances TLR2-mediated responses to Gram-negative and Gram
      positive bacteria, protein-containing LPS, peptidoglycan, and lipoteichoic acid.
      MD-2 enables TLR4 to respond to a wide variety of endotoxic LPS partial
      structures, Gram-negative bacteria, and Gram-positive lipoteichoic acid, but not
      to Gram-positive bacteria, peptidoglycan, and lipopeptide. MD-2 physically
      associates with both TLR4 and TLR2, but the association with TLR2 is weaker than
      with TLR4. Also, MD-2 and TLR2 and TLR4 enhance each other's expression. The
      highest induced genes in human monocytes stimulated with Gram-positive and Gram
      negative bacterial cell wall components are chemokine genes, and IL-8 is the
      highest induced chemokine. Both Gram-positive and Gram-negative bacteria activate
      TLR2-->MyD88-->IRAK-->TRAF-->NIK-->IKK-->NF-->kappaB signal transduction pathway
      that induces transcription of the IL-8 gene. Therefore, TLR2 is a functional
      receptor for both Gram-positive and Gram-negative bacteria and it induces
      activation of IL-8.

PMID- 11521064
TI  - Structural requirements of muramylpeptides for induction of Toll-like receptor 2
      mediated NF-kappaB activation in CHO cells.
AB  - We previously demonstrated that Gram-positive bacteria activated immune cells via
      CD14 and Toll-like receptor 2 (TLR2). Although peptidoglycan, a major constituent
      of the bacterial cell wall, substituted for whole organisms, the essential
      structure of muramylpeptides required to stimulate the cells is not clear. We
      further investigated the critical determinant for recognition by CD14 and TLR2.
      Chinese hamster ovary (CHO) fibroblasts, which do not express a functional TLR2
      transcript, were transfected with TLR2 or TLR4. These cells were exposed to
      freeze-dried Staphylococcus epidermidis and were subsequently subjected to the
      pro-inflammatory transcription factor nuclear factor-kappaB (NF-kappaB)-dependent
      CD25 expression assay. Heterologous expression of human TLR2, but not TLR4, in
      CHO cells conferred immune responsiveness to freeze-dried S. epidermidis. A
      preparation of peptidoglycan from S. epidermidis substituted for whole organisms.
      Staphylococcus aureus lytic enzyme-digested product (SEPS) from peptidoglycan
      retained the activity, but hydrolysis of the glycan backbone in SEPS by M-1 endo
      N-acetylmuramidase resulted in loss of the activity. These findings showed that
      cellular activation by Gram-positive cell wall components was mediated by TLR2,
      but not TLR4, and indicated that the glycan backbone of peptidoglycan is critical
      for TLR2-mediated NF-kappaB activation.

PMID- 11521065
TI  - Differential roles of TLR2 and TLR4 in the host response to Gram-negative
      bacteria: lessons from a lipopolysaccharide-deficient mutant of Neisseria
      meningitidis.
AB  - The inflammatory response to bacterial infections plays an important role in the
      detection and elimination of invading micro-organisms. Various components of the
      bacterial cell wall are capable of activating this pro-inflammatory response. In
      the case of Gram-negative bacteria, lipopolysaccharide (LPS) is the dominant
      trigger, although other bacterial factors are also capable of activating this
      systemic inflammatory response. Recently, Toll-like receptors (TLRs) have been
      implicated in host responses to bacterial pathogens. Specifically, TLR4 mediates
      LPS responses while TLR2 plays a broader role in the recognition of a variety of
      bacteria and bacterial antigens. The experiments in this study were designed to
      examine the role of Gram-negative cell wall components, other than LPS, and their
      cellular receptors in the host response to infection using an LPS-deficient
      mutant of Neisseria meningitidis. Although less potent than the parental strain,
      we found the LPS-deficient mutant to be a capable inducer of the inflammatory
      response in a variety of cell types. Moreover, cellular activation by this mutant
      required expression of CD14 and TLR2.

PMID- 11521066
TI  - The lipemia of sepsis: triglyceride-rich lipoproteins as agents of innate
      immunity.
AB  - Bacterial endotoxin (LPS) elicits dramatic responses in the host including
      elevated plasma lipid levels due to the increased synthesis and secretion of
      triglyceride (TG)-rich lipoproteins by the liver, and the inhibition of
      lipoprotein lipase. This cytokine-induced hyperlipoproteinemia, clinically termed
      the "lipemia of sepsis", was customarily thought to represent the mobilization of
      lipid stores to fuel the host response to infection. However, since lipoproteins
      can also bind and neutralize LPS, we hypothesize that TG-rich lipoproteins (VLDL
      and chylomicrons) are also components of an innate, non-adaptive host immune
      response to infection. Herein we review data demonstrating the capacity of
      lipoproteins to bind LPS, protect against LPS-induced toxicity, and modulate the
      overall host response to this bacterial toxin. Lastly, we propose a pathway
      whereby lipoprotein-bound LPS may represent a novel, endogenous mechanism for
      regulating the hepatic acute phase response.

PMID- 11521067
TI  - Interferon-gamma counteracts reduced endotoxin responsiveness of whole blood
      following trauma and cardiopulmonary bypass.
AB  - Accidental as well as surgical trauma has been reported to cause reduced
      endotoxin responsiveness of blood in terms of cytokine production. In this study,
      the effect of interferon-gamma (IFN-gamma) on tumour necrosis factor-alpha (TNF
      alpha)-producing capacity of whole blood after severe trauma and cardiac surgery
      was investigated. Blood samples of severely injured patients were collected at
      the first day after trauma and of cardiac surgery patients before, 4 h and 2 days
      after cardiopulmonary bypass (CPB). The blood samples were incubated with INF
      gamma (0-100 U/ml) for 20 h and subsequently lipopolysaccharide (LPS)-induced TNF
      alpha production was determined. Compared to healthy donors, LPS-induced TNF
      alpha production was significantly reduced in blood cultures of trauma patients
      on day 1 after trauma and 4 h after CPB. Pre-incubation with IFN-gamma in vitro
      increased endotoxin-induced TNF-alpha production in volunteers' and all patients'
      blood specimens in a dose-dependent manner. IFN-gamma prompted an elevation of
      cytokine synthesis in CPB patients' blood which equalled that of volunteers,
      whereas it caused a lower rise in TNF-alpha production in blood of multiply
      injured patients, reaching levels of untreated donors only after incubation with
      100 U/ml IFN-gamma. These experiments show that hyporesponsiveness of whole blood
      induced by trauma or cardiac surgery with CPB is not irreversible, but can be
      counteracted by the immunostimulant IFN-gamma. IFN-gamma, therefore, could be
      applied clinically in trauma patients or after cardiac surgery to prevent or to
      resolve infection complications.

PMID- 11521068
TI  - Cellular activating properties and morphology of membrane-bound and purified
      meningococcal lipopolysaccharide.
AB  - Neisseria meningitidis, the cause of epidemic meningitis and acute lethal sepsis,
      synthesizes surplus lipopolysaccharides (LPSs) during growth, which are released
      as outer membrane vesicles (OMV) or "blebs". Meningococcal disease severity is
      related to plasma LPS levels. We have compared the biological activities of
      native outer membrane vesicles (nOMV) to those of purified Nm-LPS (Nm-LPS) and
      LPS-depleted OMV (dOMV) prepared from N. meningitidis. The LPS content of nOMV
      was determined spectrophotometrically by quantifying KDO and by silver-stained
      SDS-PAGE gels. The morphology of the preparations was studied by transmission
      electron microscopy. The Limulus amoebocyte lysate (LAL) assay was used to
      quantify LPS in the plasma solutions. The preparations were diluted in endotoxin
      free heparin plasma to equal amounts of LPS (w/w) in the range 50-5000 pg/ml. The
      biological reactivity was tested by: (i) a monocyte target-assay (monocyte purity
      > or =96%); and (ii) a whole blood model, measuring the secretion of TNF-alpha
      and IL-6 induction of procoagulant activity in monocytes (PCA). In both models,
      nOMV induced dose-dependent cell responses (TNF-alpha, IL-6, PCA) similar to
      purified Nm-LPS, whereas dOMV induced minimal responses. However, LAL activity
      was significantly higher for nOMV than for purified Nm-LPS and dOMV. The cellular
      responses of purified Nm-LPS and nOMV were reduced (>95%) by a specific anti-CD14
      antibody.

PMID- 11521069
TI  - Examination of chlorpromazine and other amphipathic drugs on the activity of
      lipopolysaccharide antagonists, E5564 and E5531.
AB  - The synthetic antagonists of lipopolysaccharide (LPS), E5531 and E5564, are
      analogs of the lipid A portion of LPS that not only lack agonistic activity but
      also inhibit the biological effects of LPS both in vitro and in vivo. The effects
      of LPS and these synthetic antagonists have been localized to the recently
      described Toll-like receptor 4 (TLR4). A recent report indicated that the
      naturally occurring LPS antagonist Rhodobacter sphaeroides LPS loses its
      antagonist properties and gains pro-inflammatory qualities in the presence of
      chlorpromazine and other amphipathic drugs. To determine whether these reported
      actions occur with our chemically defined LPS antagonists, we examined the
      effects of chlorpromazine, fluphenazine, trifluoperazine, and lidocaine on the
      antagonism elicited by RsLPS and E5531 in U373 cells, which produce IL-6 in
      response to LPS. We also tested the effects of these amphipathic molecules on the
      LPS-neutralizing activity of RsLPS and E5564 on LPS-induced TNF-alpha release in
      human whole blood. The results indicate that neither chlorpromazine,
      fluphenazine, trifluoperazine nor lidocaine alter the activity of E5531 or E5564
      in an in vitro cell system or human whole blood. Furthermore, chlorpromazine did
      not affect the antagonistic activity of RsLPS or E5564 on IL-6 generation by
      peripheral blood mononuclear cells. Thus, based on these data, our purified
      synthetic LPS-antagonists do not appear to lose their antagonistic properties
      and/or become agonists in the presence of amphipathic agents or drugs.

PMID- 11521070
TI  - Molecular mechanisms of NF-kappaB activation induced by bacterial
      lipopolysaccharide through Toll-like receptors.
AB  - Septic shock, caused by exaggerated host responses to various microbial products
      typified by lipopolysaccharide (LPS), remains the leading cause of death in
      trauma patients. Gaining insight into the nature of host interactions with LPS
      will certainly facilitate attempts to develop effective anti-sepsis drugs.
      Tremendous progress has been made during the past few years in understanding the
      mechanisms of pathogen-induced host responses. Toll-like receptor (TLR) 4 and 2
      have been implicated as major receptors for signaling initiated by LPS and many
      other microbial products following their binding to CD14. In addition, many
      signaling intermediates involved in LPS-induced cell activation, particularly
      activation of the transcription factor NF-kappaB, have been identified and
      characterized. Further investigations with these molecules will certainly reward
      us with more effective therapeutic drugs to treat septic shock as well as many
      other inflammatory and infectious disorders.

PMID- 11521071
TI  - LPS-induced immune response in Drosophila.
AB  - The study of the regulation of the inducible synthesis of antimicrobial peptides
      in Drosophila melanogaster has established this insect as a powerful model in
      which to study innate immunity. In particular, the molecular characterization of
      the regulatory pathway controlling the antifungal peptide drosomycin has revealed
      the importance of Toll receptors in innate immunity. We report here that
      injection of LPS into flies induces an immune response, suggesting that LPS
      receptors are used in Drosophila to detect Gram-negative bacteria infection. We
      have identified in the recently sequenced genome of Drosophila eight genes coding
      for Toll-like receptors in addition to Toll, which may function as LPS receptors.
      However, overexpression of a selection of these genes in tissue-culture cells
      does not result in up-regulation of the antibacterial peptide genes. These
      results are discussed in light of the recent data from genetic screens aimed at
      identifying the genes controlling the antibacterial response in Drosophila.

PMID- 11521072
TI  - Clinically-oriented therapies in sepsis: a review.
AB  - Our insight of the sepsis response has evolved to encompass not only the pro
      inflammatory but also an anti-inflammatory reaction following infection. Clinical
      trials have been designed to target either bacterial products, endotoxin in
      particular, or mediators involved in the sepsis response, but until recently the
      majority of them have given unfavorable results. In this article, we provide a
      scope of clinical trials that have been done in immunomodulation during sepsis
      whether or not they provide positive results. We will also discuss some of the
      reasons why those studies have been disappointing. Current and future trials with
      a better assessment of inflammatory status of patients and better-defined
      outcomes such as organ dysfunction are now underway.

PMID- 11521073
TI  - MALP-2, a Mycoplasma lipopeptide with classical endotoxic properties: end of an
      era of LPS monopoly?
AB  - Although some activities of LPS are shared by other bacterial components, for
      half a century LPS has been regarded as unique in displaying many
      pathophysiological activities. Here we report on a synthetic lipopeptide, MALP-2
      from Mycoplasma fermentans, which expresses potent endotoxin-like activity and
      whose lethal toxicity is comparable to that of LPS. With the exception of the
      Limulus lysate gelation test, in which MALP-2 was approximately 1000-fold less
      active than LPS, the synthetic lipopeptide induced all activities tested for, and
      in most cases to an extent comparable to that of LPS. Unlike LPS, the biological
      activities of MALP-2 were expressed both in LPS-responder and in LPS-non
      responder mice (BALB/c/l, C57BL10/ScCr), indicating that MALP-2 signaling, unlike
      that of LPS, is not transduced via the Toll-like receptor (Tlr) 4 protein.MALP-2
      expressed no toxicity in normal or sensitized Tlr2 knockout (Tlr2(-/-)) mice
      indicating that its toxic activity is induced via Tlr2 signaling. The
      phenomenology of the lethal shock induced by MALP-2 in normal or sensitized mice,
      i.e. the kinetics of its development and symptoms of illness exhibited by the
      treated animals, was very reminiscent of the lethal shock induced by LPS.

PMID- 11521074
TI  - Plasma constituents regulate LPS binding to, and release from, the monocyte cell
      surface.
AB  - Innate immunity to Gram-negative bacteria involves regulated mechanisms that
      allow sensitive but limited responses to LPS. Two important pathways that lead to
      host cell activation and LPS deactivation involve: (i) LPS interactions with CD14
      and Toll-like receptor 4 on cells (activation); and (ii) LPS sequestration by
      plasma lipoproteins (deactivation). Whereas these pathways were previously
      thought to be independent and essentially irreversible, we found that they are
      connected by a third pathway: (iii) the movement of LPS from host cells to plasma
      lipoproteins. Our data show that, in the presence of human plasma, LPS binds
      transiently to monocyte surfaces and then moves from the cell surface to plasma
      lipoproteins. Soluble CD14 enhances LPS release from cells in the presence of
      lipoproteins, whereas LPS binding protein and phospholipid transfer protein do
      not. The transfer of cell-bound LPS to lipoproteins is accompanied by reduced
      cell responses to the LPS, suggesting that the movement of LPS from leukocytes
      into lipoproteins may attenuate host responses to LPS in vivo. Preliminary data
      suggest that changes that occur in the plasma after trauma or during sepsis
      decrease LPS binding to leukocytes while greatly increasing the rate of LPS
      release from cells.

PMID- 11521075
TI  - Cytosolic protein ubiquitylation in normal and endotoxin stimulated human
      peripheral blood mononuclear cells.
AB  - The ubiquitin-proteasome pathway is regarded as playing a crucial role in protein
      breakdown in inflammation and sepsis as well as in the regulation of inflammatory
      cell responses. In this pathway, ubiquitylation of target proteins is believed to
      act as a recognition signal for degradation by the 26S proteasome. As yet neither
      the ubiquitylation rate of cytosolic proteins, as a result of the total ubiquitin
      protein ligase (tUbPL) activity, nor the specific ubiquitylation of calmodulin
      (ubiquitin-calmodulin ligase, uCaM-synthetase) has been determined in human
      mononuclear cells. Therefore, we studied cytosolic protein ubiquitylation in
      normal and in endotoxin (LPS)-stimulated human peripheral blood mononuclear cells
      (PBMNCs).PBMNCs from healthy volunteers were incubated with 0 or 100 ng/ml LPS
      for 18 h. Cytosolic extracts were obtained by hypotonic lysis and
      ultracentrifugation. TUbPL was measured as [(125)I]-[CT]-ubiquitin incorporation
      into the sum of cytosolic proteins. UCaM-synthetase activity was quantified with
      the fluphenazine (FP)-Sepharose affinity adsorption test. Endotoxin stimulation
      appears to inhibit tUbPL 3.7 +/- 2.7-fold to 48 +/- 43 fkat/mg (n = 6). UCaM
      synthetase in cultures (n = 5) without endotoxin was determined to be 91 +/- 32
      fkat/mg +Ca(2+) and 29 +/- 23 fkat/mg -Ca(2+). With endotoxin uCaM-synthetase was
      138 +/- 73 fkat/mg +Ca(2+) and 14 +/- 22 fkat/mg -Ca(2+). Ca(2+)-specificity
      (ratio +/- Ca(2+)) of uCaM-synthetase increases from 3.1 without LPS to 10 after
      LPS stimulation, which was caused by a 2-fold decrease in minus Ca(2+) activity
      and a 1.5-fold increase in plus Ca(2+) activity. The data indicate specific
      regulatory effects of endotoxin on the cytosolic ubiquitylation systems in human
      PBMNCs.

PMID- 11521076
TI  - MD-2 binds to bacterial lipopolysaccharide.
AB  - Many LPS binding proteins have been described, but the exact nature of the LPS
      receptors that signal cells remains unclear. MD-2 is a molecule that is found in
      association with Toll-like receptor 4, which has been shown to be a receptor for
      LPS. We have produced human MD-2 in baculovirus and tested it for LPS binding. MD
      2 binds the lipid A region of LPS without the need for LPS binding protein. These
      data suggest that MD-2 may be binding LPS as part of the TLR4 receptor complex.

PMID- 11521077
TI  - Lipopolysaccharide biosynthesis: which steps do bacteria need to survive?
AB  - A detailed knowledge of LPS biosynthesis is of the utmost importance in
      understanding the function of the outer membrane of Gram-negative bacteria. The
      regulation of LPS biosynthesis affects many more compartments of the bacterial
      cell than the outer membrane and thus contributes to the understanding of the
      physiology of Gram-negative bacteria in general, on the basis of which only
      mechanisms of virulence and antibiotic resistance can be studied to find new
      targets for antibacterial treatment. The study of LPS biosynthesis is also an
      excellent example to demonstrate the limitations of "genomics" and "proteomics",
      since secondary gene products can be studied only by the combined tools of
      molecular genetics, enzymology and analytical structural biochemistry. Thus, the
      door to the field of "glycomics" is opened.

PMID- 11521078
TI  - Cloning, sequencing, and functional analysis of three glycosyltransferases
      involved in the biosynthesis of the inner core region of Klebsiella pneumoniae
      lipopolysaccharide.
AB  - The genes encoding the 3-deoxy-D-manno-oct-2-ulosonic acid (Kdo) transferase
      (waaA) and heptosyltransferases I (waaC) and II (waaF) in Klebsiella pneumoniae
      were cloned from a DNA library by functional complementation of corresponding
      Escherichia coli and Salmonella enterica mutants. Sequence analyses revealed
      extensive homologies of the deduced proteins to their counterparts in other
      Enterobacteriaceae. However, differences were evident with regard to the
      chromosomal organization of the genes. To perform in vitro studies, the waaA,
      waaC and waaF genes were subcloned and expressed in the Gram-positive host
      Corynebacterium glutamicum. WaaA was characterized as a bifunctional enzyme
      capable of transferring two Kdo residues to a synthetic bisphosphorylated
      tetraacyl-lipid A precursor of E. coli (compound 406). In contrast, waaC and waaF
      were shown to encode specific glycosyltransferases catalyzing the consecutive
      transfer of two L-glycero-D-manno-heptose residues to Kdo(2)-406.

PMID- 11521079
TI  - Lipopolyamines as a therapeutic strategy in experimental Gram-negative bacterial
      sepsis.
AB  - Lipopolyamines are a class of polycationic amphiphilic compounds that have been
      shown to bind with high affinity to polyanionic macromolecules, including both
      DNA and bacterial lipopoly-saccharide (LPS). One of these compounds, termed
      DOSPER (1,3-di-oleoyloxy-2-(6-carboxyl-spermyl)- propylamide), is non-cytotoxic
      and has been shown to inhibit LPS-mediated cytokine release and lethality in
      endotoxin challenge models. In the study reported here, the activity of DOSPER
      was tested in neutropenic rats with invasive Gram-negative bacteremia caused by
      Pseudomonas aeruginosa. DOSPER alone was ineffective (0/8) at influencing
      mortality, but provided a significant survival advantage if administered in
      combination with a bactericidal antibiotic, ceftazidime (10/12; P<0.05).
      Ceftazidime alone was partially protective (6/12) while the control group had no
      survivors (0/8). DOSPER administration markedly reduced circulating endotoxin
      levels (P<0.01) and interleukin-6 levels (P<0.05) but had no significant effect
      on bacteremia and bacterial concentrations of P. aeruginosa in liver or spleen
      tissue. Lipopolyamines may be potentially valuable as a therapeutic adjunct in
      treatment of Gram-negative bacterial sepsis.

PMID- 11521080
TI  - Mouse B1 cell line responds to lipopolysaccharide via membrane-bound CD14.
AB  - The role of membrane-bound CD14 in the response of mouse B1 cell lines to
      lipopolysaccharide (LPS) was studied. The surface profile of mouse TH2.52 B cells
      was positive for CD5, IgM, B220, CD11b and F4/80, suggesting that TH2.52 cells
      carried the typical phenotype of B1 cells. Furthermore, TH2.52 B1 cells were
      found to express membrane-bound CD14, which plays a critical role in LPS
      recognition. TH2.52 B1 cells responded to a very low concentration of LPS and
      exhibited: (i) augmentation of DNA synthesis; (ii) activation of nuclear factor
      (NF)-kappaB; and (iii) phosphorylation of extracellular signal regulated kinase
      1/2 (Erk1/2). They were markedly inhibited by anti-CD14 antibody. Therefore, the
      expression of membrane-bound CD14 was suggested to provide high sensitivity to
      LPS for TH2.52 B1 cells.

PMID- 11521081
TI  - CD14: a bridge between innate immunity and adaptive IgE responses.
AB  - Total IgE levels are known to be under genetic control. Linkage studies have
      indicated that one or more loci on chromosome 5q may control total IgE, as well
      as asthma and bronchial hyperresponsiveness to non-specific stimuli. Our group
      has undertaken a systematic analysis of chromosome 5q, and has recently
      characterized five single nucleotide polymorphisms at position -1619, -1359, 
      1145, -809, and -159 in the promoter of the gene encoding CD14, the myeloid
      pattern recognition receptor that is critical for efficient innate immune
      responses to lipopolysaccharide and bacterial ligands. Individuals homozygous for
      the three major CD14 haplotypes found in the Children Respiratory Study
      population (n = 390) were analyzed for serum levels of total IgE and soluble
      CD14. A strong inverse correlation was found between these two parameters, i.e.
      carriers of the -1359T/-1145A/-159C haplotype had the highest levels of IgE, and
      the lowest levels of sCD14. Conversely, carriers of the -1359G/-1145G/-159T
      haplotype had the highest levels of sCD14 and the lowest IgE values. Our results
      suggest that genetic variation in CD14, a key gene of innate immunity, may
      modulate the effects that exposure to bacterial ligands has on the development of
      Th2 responses.

PMID- 11521082
TI  - A novel acute phase marker in cattle: lipopolysaccharide binding protein (LBP).
AB  - The host response to infection, the "acute phase response" is a highly conserved
      series of physiological reactions including marked changes in concentrations of
      plasma proteins. These proteins have been shown to participate in the immune
      response to infections. Several recent studies have elevated the role of acute
      phase proteins (APPs) as predictive markers in infection. APPs such as serum
      amyloid A and haptoglobin but not C-reactive protein (CRP) have been identified
      as markers of inflammation in cattle. In humans, lipopolysaccharide (LPS) binding
      protein (LBP) has certain biological functions in host defence and participates
      in acute phase reactions. We measured plasma levels of LBP in a group of 20
      calves experimentally infected with Gram-negative Mannheimia haemolytica
      (Pasteurella) in comparison to haptoglobin, the most widely studied APP in
      cattle. In infected calves, LBP levels rose significantly 6 h after infection,
      reaching a maximum at 24 h. Haptoglobin concentrations significantly rose after
      12 h, and peak responses were measured 48 h after infection. Thus, LBP may prove
      to be a diagnostic marker in cattle infection and is faster than haptoglobin in
      detecting sepsis.

PMID- 11521083
TI  - The involvement of Ran GTPase in lipopolysaccharide endotoxin-induced responses.
AB  - By functional cloning, we have established that Ran GTPase is involved in LPS
      induced signal transduction. This has been accomplished by several functional
      comparisons of the two cDNAs, Lps(n)/Ran (or RanT/n) and Lps(d)/Ran (or RanC/d),
      which were isolated from cDNA libraries of LPS responder and hyporesponder mice,
      respectively. The letter n refers to the "normal" phenotype and the letter d
      refers to the "deficient" phenotype. Consistent with our previous results, more
      animal studies indicated that adenoviral transduction of RanC/d cDNA, but not
      RanT/n cDNA, into sensitive mice conferred significant resistance against
      endotoxin challenge. Thus the incorporation of RanC/d cDNA into gene therapy
      protocols as a therapeutic sequence remains very attractive. At steady state,
      hematopoietic cells transduced with RanC/d cDNA led to about a 10-fold increase
      in exogenous Ran protein compared with RanT/n cDNA. Furthermore, our cumulative
      data suggest that a slight elevation of Ran protein in B cells enhances LPS
      responsiveness, but the same elevation of Ran in macrophages does not. On the
      other hand, a high level of overexpression of Ran in both macrophages and B cells
      down-regulates LPS signal transduction. Thus LPS-induced signal transduction in
      macrophages and B cells is likely to occur via different signaling pathways.

PMID- 11521084
TI  - Bacterial modification of LPS and resistance to antimicrobial peptides.
AB  - Antimicrobial peptides (APs) are ubiquitous in nature and are thought to kill
      micro-organisms by affecting membrane integrity. These positively charged
      peptides interact with negative charges in the LPS of Gram-negative bacteria. A
      common mechanism of resistance to AP killing is LPS modification. These
      modifications include fatty acid additions, phosphoethanolamine (PEtN) addition
      to the core and lipid A regions, 4-amino-4-deoxy-L-arabinose (Ara4N) addition to
      the core and lipid A regions, acetylation of the O-antigen, and possibly
      hydroxylation of fatty acids. In Salmonella typhimurium, LPS modifications are
      induced within host tissues by the two-component regulatory systems PhoPQ and
      PmrAB. PmrAB activation results in AP resistance by Ara4N addition to lipid A
      through the activation of at least 8 genes, 7 of which are transcribed as an
      operon. Loss of this operon and, therefore, Ara4N LPS modification, affects S.
      typhimurium virulence when administered orally. Transposon mutagenesis of Proteus
      mirabilis also suggests that LPS modifications affect AP resistance and virulence
      phenotypes. Therefore, LPS modification in Gram-negative bacteria plays a
      significant role during infection in resistance to host antimicrobial factors,
      avoidance of immune system recognition, and maintenance of virulence phenotypes.

PMID- 11521085
TI  - Structural variability and originality of the Bordetella endotoxins.
AB  - Structural studies of Bordetella endotoxins (LPSs) have revealed remarkable
      differences: (i) between their LPSs and those of other bacterial pathogens; (ii)
      among the LPSs of the seven identified Bordetella species; and (iii) among the
      LPSs of some Bordetella strains. The lipid As have the "classical"
      bisphosphorylated diglucosamine backbone but tend to have fewer and species
      specific fatty acid components compared to those of other genera. Nevertheless,
      three strains of B. bronchiseptica have at least three different fatty acid
      distributions; however, the recently identified B. hinzii and B. trematum LPSs
      had identical lipid A structures. The B. pertussis core is a dodecasaccharide
      multi-branched structure bearing amino and carboxylic groups. Another unusual
      feature is the presence of free amino sugars in the central core region and a
      complex distal trisaccharide unit containing five amino groups of which four are
      acetylated and one is methylated. The B. pertussis LPS does not have O-chains and
      that of B. trematum had only a single O-unit, unlike the LPSs of all the other
      species of the smooth-type. The O-chain-free cores of non-B. pertussis LPSs were
      always built on the B. pertussis core model but most were species-specifically
      incomplete. The LPS structures of three B. bronchiseptica strains were found to
      be different from each other. The O-chains of B. bronchiseptica and B.
      parapertussis were almost identical and had some features in common with B.
      hinzii O-chain. Serological analyses are consistent with the determined LPS
      structures.

PMID- 11521086
TI  - Outer membrane protein A (OmpA), peptidoglycan-associated lipoprotein (PAL), and
      murein lipoprotein (MLP) are released in experimental Gram-negative sepsis.
AB  - We previously showed that Escherichia coli bacteria incubated in normal human
      serum release complexes that contain three conserved Gram-negative bacterial
      outer membrane proteins (OMPs) and LPS. We have identified the OMPs as outer
      membrane protein A (OmpA), peptidoglycan-associated lipoprotein (PAL), and murein
      lipoprotein (MLP). These OMPs are conserved among enteric Gram-negative bacteria
      and are bound by IgG in antisera raised to heat-killed rough bacteria such as E.
      coli J5 (J5 IgG). The present experiments were performed to further analyze the
      release of these OMPs in a rat wound infection model of sepsis. Plasma was
      collected from thermally injured rats with E. coli O18 sepsis and filtered. LPS
      was affinity-purified from plasma filtrates using monoclonal antibody specific
      for the O-polysaccharide side chain of E. coli O18 LPS. Plasma filtrates were
      also incubated with J5 IgG conjugated to magnetic beads. Affinity-purified
      samples were analyzed for the OMPs by immunoblotting. OmpA, PAL, and MLP were
      released into septic rat blood in complexes with LPS. PAL was consistently
      present in samples affinity-purified using J5 IgG. The results indicate that
      OmpA, PAL, and MLP are released and circulate in experimental Gram-negative
      sepsis and suggest that a proportion of released OMPs are tightly associated with
      LPS.

PMID- 11521087
TI  - Regulated covalent modifications of lipid A.
AB  - Regulated covalent modifications of lipid A are implicated in virulence of
      pathogenic Gram-negative bacteria. The Salmonella PhoP/PhoQ-activated gene pagP
      is required for resistance to cationic antimicrobial peptides and for
      biosynthesis of hepta-acylated lipid A species containing palmitate.
      Interestingly, pagP encodes an unusual enzyme of lipid A biosynthesis localized
      in the outer membrane, whereas all previously characterized lipid A enzymes are
      cytoplasmic or associated with the inner membrane. PagP is not unique, however,
      as pagL encodes another outer membrane enzyme in Salmonella that deacylates the 3
      position of lipid A.S. typhimurium also synthesizes S-2-hydroxymyristate modified
      lipid A in a PhoP/PhoQ-dependent manner. We postulated that 2-hydroxylation might
      be catalyzed by a novel dioxygenase. Using well-characterized dioxygenase
      sequences as probes, tBLASTn searches revealed unassigned open reading frame(s)
      with similarity to mammalian aspartyl beta-hydroxylases in bacteria known to make
      2-hydroxyacylated lipid A. The S. typhimurium aspartyl beta-hydroxylase homologue
      (lpxO) was cloned and expressed in Escherichia coli K-12, which does not contain
      lpxO. Analysis of the resulting construct revealed that lpxO expression induces
      O(2)-dependent formation of 2-hydroxymyristate-modified lipid A in E. coli. LpxO
      may be an inner membrane enzyme that catalyzes Fe(2+)/ascorbate/alpha
      ketoglutarate dependent hydroxylation of lipid A. We propose that 2
      hydroxymyristate released from LPS inside infected animal cells might be
      converted to 2-hydroxymyristoyl coenzyme A, a potent inhibitor of protein N
      myristoyl transferase.

PMID- 11521088
TI  - Immunodepression in sepsis and SIRS assessed by ex vivo cytokine production is
      not a generalized phenomenon: a review.
AB  - Sepsis and non-infectious systemic inflammatory response syndrome (SIRS) are
      paradoxically associated with an exacerbated production of cytokines, as assessed
      by their presence in biological fluids, and a diminished ability of circulating
      leukocytes to produce cytokine upon in vitro activation. In this review, we
      depict that the observed cellular hyporeactivity is not a global phenomenon and
      that some signalling pathways are unaltered and allow the cells to respond
      normally to certain stimuli. Furthermore, we illustrate that during sepsis and
      SIRS, cells derived from tissues are either fully responsive to ex vivo stimuli
      or even primed, in contrast to cells derived from hematopoietic compartments
      (blood, spleen, etc.) which are hyporeactive. In addition to cytokine production,
      nuclear factor-kappa B (NF-kappa B) status within leukocytes can be used as a
      useful marker of hypo- or hyper-reactivity. We illustrate that the immune
      depression reported in sepsis and SIRS patients, often revealed by a diminished
      capacity of leukocytes to respond to lipopolysaccharide, is not a generalized
      phenomenon and that SIRS is associated with a compartmentalized responsiveness
      which involves either anergic or primed cells.

PMID- 11521089
TI  - Chemical structure and biological activity of a lipid A component from
      Helicobacter pylori strain 206.
AB  - The chemical structure of a lipid A, which was obtained as a minor component from
      lipopolysaccharide of Helicobacter pylori strain 206-1, was determined to be a
      glucosamine beta-(1 -6) disaccharide 1-(2-aminoethyl)phosphate acylated by (R)-3
      hydroxyoctadecanoic acid, (R)-3- hydroxyhexadecanoic acid, and (R)-3
      (octadecanoyloxy)octadecanoic acid at the 2-, 3- and 2'-positions, respectively.
      Compared with the other major lipid A from the same strain, which was previously
      reported [Suda Y, Ogawa T, Kashihara W et al. Chemical structure of lipid A from
      Helicobacter pylori strain 206-1 lipopolysaccharide. J Biochem 1997; 121: 1129-
      1133], the structure was very similar with one exception. An (R)-3
      hydroxyhexadecanoic acid was present at the 3-position of the novel lipid A
      component. The structure is apparently identical to one of the proposals by Moran
      et al. [Moran AP, Lindner B, Walsh EJ. Structural characterization of the lipid A
      component of Helicobacter pylori rough- and smooth-form lipopolysaccharides. J
      Bacteriol 1997; 179: 6453--6463], who concluded the same structure as the so
      called major lipid A from the H. pylori strain NCTC 11637 but without isolating a
      homogeneous component. The endotoxic properties and pro-inflammatory cytokine
      inducing activities of this novel tetra-acyl type lipid A were lower than those
      of previously reported major tri-acyl type lipid A.

PMID- 11521090
TI  - Cytokine synthesis in the liver of endotoxin-tolerant and normal rats during
      hemorrhagic shock.
AB  - In the present study the effects of endotoxin tolerance on hemorrhagic shock were
      investigated with particular focus on hepatic alterations. The following
      questions were addressed: (i) does hemorrhagic shock induce cytokine formation
      and heat shock response in the liver; and (ii) does endotoxin tolerance alter
      these reactions. Endotoxin tolerance was induced by repetitive daily injections
      of LPS for 5 days. Hemorrhagic shock was induced by hypovolemia (MAP 35 +/- 5
      mmHg). After 3 h, the animals were resuscitated by re-infusion of homologous
      blood. m-RNA was isolated from liver biopsies and the mRNA levels of tumor
      necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), interleukin-10 (IL-10)
      and heat shock protein 70 (HSP-70) were determined by RT-PCR. TNF-alpha was
      measured by ELISA in serum samples and in the supernatants of whole blood
      cultures. It was found that endotoxin tolerance reduced mortality caused by
      hemorrhagic shock from 80% to 20%. In parallel, TNF-alpha production in response
      to LPS in vivo and in vitro was significantly decreased. During hemorrhage and
      after resuscitation. increased mRNA levels were detected in hepatic biopsies for
      TNF-alpha, IL-6, IL-10 and HSP-70, with highest levels immediately after re
      infusion. Endotoxin-tolerant rats produced significantly lower levels of TNF
      alpha, while no differences were found for IL-10 and HSP-70. Within 30 min after
      reperfusion, significantly higher levels of IL-6 mRNA were found in hepatic
      biopsies from tolerant rats; these differences disappeared 2 h after reperfusion.

PMID- 11521091
TI  - Structural and serological characterisation of the O-antigenic polysaccharide of
      the lipopolysaccharide from Acinetobacter strain 96 (DNA group 11).
AB  - A polysaccharide containing D-Manp, L-Fucp (6-deoxygalactopyranose, fucose) and D
      GlcpNAc was isolated by mild acid hydrolysis, followed by gel-permeation
      chromatography, from the lipopolysaccharide derived from Acinetobacter strain 96
      (DNA group 11). The structure of the O-antigen was determined by compositional
      analysis and NMR spectroscopy of the polysaccharide as: [carbohydrate structure
      see text] A monoclonal antibody obtained after immunization of mice with heat
      killed bacteria of Acinetobacter strain 96 was shown to bind to the O-antigen and
      did not cross-react with any Acinetobacter O-antigen of known structure.

PMID- 11521092
TI  - A monoclonal antibody with specificity for the genus Klebsiella binds to a common
      epitope located in the core region of Klebsiella lipopolysaccharide.
AB  - A mouse monoclonal antibody (mAb) which has been obtained after immunization of
      mice with heat-killed Klebsiella pneumoniae strain R20/O1(-) followed by standard
      plasmacytoma cell fusion protocols was investigated for its ability to identify
      various species of the genus Klebsiella. Based on the published observation that
      the antibody binds to an epitope located in the core region of lipopolysaccharide
      (LPS) of strain R20/O1(-), we tested whether this epitope is shared and exposed
      by other species of the genus Klebsiella. The antibody was able to bind to LPS of
      clinical isolates of K. pneumoniae (n = 77), K. oxytoca (n = 50), K. terrigena (n
      = 49) and K. planticola (n = 50) in 93%, 98%, 96% and 100%, respectively, but did
      not bind to LPS of other Gram-negative genera (n = 159) as tested by Western
      blots and dot blots using proteinase K-digested whole cell lysates as antigens.
      Western blot analyses indicated that the antibody bound only to those LPS
      molecules which did not carry an O-antigen and that the antibody is thus
      different from those already published.

PMID- 11521093
TI  - Synthesis and immunochemical characterization of neoglycoproteins containing
      epitopes of the inner core region of Pseudomonas aeruginosa RNA group I
      lipopolysaccharide.
AB  - The disaccharide allyl 2-acetamido-2-deoxy-alpha-D-galactopyranosyl-(1-->3)-7-O
      carbamoyl-L-glycero-alpha-D-manno-heptopyranoside 5 (GalNAc-cmHep-allyl) was
      synthesized starting from 1 and 2. Compound 5, cmHep-allyl and the disaccharide
      cmHep-(1-->3)-Hep-allyl were converted into cysteamine-spacered derivatives and
      conjugated to bovine serum albumin (BSA) to yield the neoglycoconjugates 7--9,
      respectively. These conjugates were used to immunize mice and to prepare
      monoclonal antibodies (mAbs) which were characterized in comparison to mAbs
      obtained after immunization with heat-killed Pseudomonas aeruginosa strain H4.
      Two antibodies obtained after immunization with the neoglycoconjugates bound
      strongly to cmHep-BSA and with lower affinity to cmHep-Hep-BSA but did not bind
      to GalNAc-cmHep-BSA or to H4 LPS. Another antibody obtained after immunization
      with heat-killed bacteria bound to LPS and GalNAc-cmHep-BSA but not to cmHep-Hep
      BSA or cmHep-BSA

PMID- 11521094
TI  - Structural and biological characterisation of a novel tetra-acyl lipid A from
      Escherichia coli F515 lipopolysaccharide acting as endotoxin antagonist in human
      monocytes.
AB  - We here report on the structural analysis of a novel tetra-acyl lipid A (LA
      (tetra) ) isolated from Escherichia coli deep rough (Re)-mutant strain F515. In
      addition to the biologically active hexa-acyl E. coli-type lipid A (compound
      506), this incompletely acylated lipid A was found to be also present in the
      native LPS. Its structure was studied without further derivatisation by chemical
      analysis, matrix-assisted laser desorption/ionization mass spectrometry, and one-
      and two-dimensional (1)H- and (13)C-NMR spectroscopy. It was found to be
      structurally distinct from the tetra-acyl lipid A biosynthetic precursor Ia
      (compound 406) in lacking the primary (R)-3-hydroxytetradecanoic acid 14:0(3-OH)
      in position 3' ester-linked to the 'non-reducing' glucosamine (GlcN II). The
      hydroxyl group at the (R)-3-hydroxytetradecanoic acid attached to position 2' of
      GlcN II was found to be substituted by dodecanoic acid (12:0), thus forming a
      dodecanoyloxytetradecanoyl residue 14:0[3-O(12:0)]. The acylation pattern at the
      'reducing' GlcN I was identical to that of compound 406 in having two primary (R)
      3-hydroxy tetradecanoic acid residues [14:0(3-OH)] attached to positions 3 (ester
      linked) and 2 (amide-linked), respectively. In human mononuclear cells (hMNC) the
      new LA (tetra) antagonized LPS-induced release of interleukin-1 (IL-1),
      interleukin-6 (IL-6), and tumor necrosis factor (TNF) in a dose-dependent manner
      with identical antagonistic potency as compared with compound 406. Also like
      compound 406, it was found to be an agonist in murine macrophage-like J774.1
      cells.

PMID- 11521095
TI  - Influence of acyl chain fluidity on the lipopolysaccharide-induced activation of
      complement.
AB  - Lipopolysaccharides (LPSs, endotoxins) are the major amphiphilic constituents of
      the outer leaflet of the outer membrane of Gram-negative bacteria. They are known
      to activate the complement cascade to form lytic membrane pores. Here, we study
      the influence of the fluidity of the acyl chains of LPSs and lipid As on the
      formation of lytic pores. To this end, we have performed electrical measurements
      on asymmetric planar endotoxin/phospholipid bilayers as a reconstitution model of
      the outer membrane using two deep rough mutant LPSs (from Escherichia coli
      strains WBB01 and WBB25) and two lipid As (from E. coli WBB25 and Rhodobacter
      sphaeroides). The two LPSs and the two lipid As each differ in their acylation
      pattern which is correlated with the fluidity. The addition of human serum to the
      endotoxin side of the bilayers led to the formation of membrane pores, and pore
      formation correlated in each case with acyl chain fluidity, i.e. time required
      for the first lytic pore to be formed was shorter for the more fluid endotoxin.
      Furthermore, in the case of LPSs, the activation rate was higher for the more
      fluid membrane and the respective bacteria had a higher susceptibility to the
      growth inhibitory action of serum.

PMID- 11521096
TI  - TNF-alpha hyper-responses to Gram-negative and Gram-positive bacteria in
      Propionibacterium acnes primed or Salmonella typhimurium infected mice.
AB  - IFN-gamma-dependent hypersensitivity to LPS is inducible in mice by infection or
      pre-treatment with killed bacteria. Hypersensitive mice exhibit enhanced
      inflammatory responses to LPS, including the overproduction of TNF-alpha. Using
      Lps(n) BALB/c and Lps(d) BALB/c/l mice, primed with Propionibacterium acnes or
      infected with Salmonella typhimurium, we show that concurrently to
      hypersensitivity to LPS, a hypersensitivity to other constituents of killed Gram
      negative or Gram-positive bacteria and to staphylococcal enterotoxin B (SEB)
      develops. The TNF-alpha hyper-responses in sensitized mice induced by different
      Gram-positive bacteria, are generally weaker than those by Gram-negative bacteria
      and vary significantly, due to the absence of a common, LPS-equivalent component.
      Using IFN-gamma R(-/-) and the respective wild-type mice, we demonstrate that
      although sensitization to LPS and killed Listeria monocytogenes is exclusively
      IFN-gamma-dependent, an IFN-gamma-independent, moderate sensitization to certain
      TNF-alpha-inducing constituents in bacteria may develop in parallel.

PMID- 11521098
TI  - [Pelvic irradiation and anorectal function: a plea for sphincter-preserving
      radiation therapy].

PMID- 11521099
TI  - [Expandable metal stents in palliative treatment of malignant colorectal
      stricture. A report of 17 consecutive patients].
AB  - OBJECTIVE: Several endoscopic procedures have been used to avoid a colostomy in
      palliative treatment of occlusive colorectal cancer. The aim of this study was to
      evaluate in intent to treat the long term effectiveness and safety of self
      expanding metal stents as a palliative treatment in patients with neoplastic
      colonic obstruction. PATIENTS AND METHODS: From December 1997 to June 2000,
      seventeen patients were treated with 21 colonic stents. Sites of obstruction were
      high rectum in 3, sigmoid in 11 and left colon in 3. RESULTS: Stent placement was
      successful in 16/17 patients (94%). Relief of bowel obstruction occurred in 13
      patients (74%) in the first 48 hours. Expandable metal stent achieved an
      effective bowel transit until death in 9 of the 17 patients (53%). Clinical
      complications occurred in 6 patients (35%): 2 perforations, 2 migrations, 1
      rectal bleeding and 1 dislocation of the stent. Subsequent colostomy was done in
      5 patients. CONCLUSION: Colonic stenting is an alternative palliative treatment
      in malignant colorectal stricture. However, morbidity and need for subsequent
      colostomy should be taken into account.

PMID- 11521100
TI  - [Preoperative prognostic factors for squamous cell carcinomas of the thoracic
      esophagus].
AB  - AIM OF THE STUDY: To identify preoperative survival prognostic factors in
      patients with resectable squamous cell carcinoma of the thoracic esophagus.
      POPULATION: From January 1982 to September 1999, 868 patients underwent surgery
      for esophageal carcinoma in our department, including 493 for squamous cell
      carcinoma of the thoracic esophagus. The following parameters were
      retrospectively included in univariate and multivariate analysis: age, sex,
      undernutrition, dysphagia, tumor diameter and nodal involvement on the CT-scan,
      preoperative treatment, surgical technique, curative resection, pTNM
      classification, histologic type and postoperative complications. The actuarial
      survival was determined. RESULTS: Survival prognostic factors were dysphagia,
      nodal involvement on CT-scan and depth of tumor invasion at pathological
      examination. Three groups of patients were identified on the two preoperative
      variables: group 1: patients without dysphagia (n=102), group 2: patients with
      dysphagia but without nodal involvement on the CT- scan (n=244), group 3:
      patients with dysphagia and with nodal involvement on the CT- scan (n=147). The
      median survivals were 62.4, 19.1 and 14.4 months in groups 1, 2 and 3,
      respectively, and 5-year actuarial survivals were 50%, 21% and 11% (P<0.009).
      CONCLUSION: Our study confirms that dysphagia and nodal involvement on the CT
      scan are simple preoperative prognostic factors in patients with resectable
      squamous cell carcinoma of the thoracic esophagus.

PMID- 11521101
TI  - [Gastrointestinal stromal tumors].

PMID- 11521102
TI  - [Celiac disease of the adult].

PMID- 11521103
TI  - [Portal vein thrombosis: is anticoagulation indicated?].

PMID- 11521104
TI  - [Hepatitis C virus-related cirrhosis: is antiviral treatment mandatory?].

PMID- 11521105
TI  - [Evaluation of three testing strategies for detection of hepatitis C in a
      hospital medical consultation and in an HIV testing center].
AB  - AIMS: Testing for hepatitis C virus (HCV) is recommended. The purpose of this
      study was to evaluate the efficacy of HCV testing in a medical consultation
      without an appointment and in an HIV testing center based on three testing
      strategies: 1997 French Consensus Conference, "Lettre de la Direction Generale de
      la Sante" (January 1996), and extension to other risk factors. PATIENTS AND
      METHODS: For 6 months a free blood test was offered to any patient with a risk
      factor according to the literature. RESULTS: There were 1 736 new patients at the
      medical consultation and 1 616 at the testing center. The patients were younger
      at the testing center than at the medical consultation (31.1 vs 43.3 years;
      P<0.001). Acceptance of screening was better at the testing center (97.8% vs
      75.2%; P<0.001). There were more patients exposed to one of the risk factors at
      the testing center (31.2% vs 13.9%; P<0.001). Tests were more efficient at the
      testing center: 30 HCV positive patients/1 616 (1.86%) vs 11/1 736 (0.63%,
      P<0.01). Tests based on the 1997 French Consensus Conference provided detection
      in 27/30 (90%) of HCV positive patients at the testing center but only 4/11
      (36.3%) at the medical consultation (P<0.01). CONCLUSION: Testing was effective
      in both places but was more efficient at the testing center. Efficacy of the
      testing strategies differs significantly according to the place of screening. At
      the testing center, screening can be restricted to patients with a history of
      intravenous drug use and blood transfusion. At the medical consultation,
      screening should be extended to other risk factors.

PMID- 11521106
TI  - [Hepatitis E virus infection: epidemiology and prevention].

PMID- 11521107
TI  - [HIV-HBV coinfection and the liver].

PMID- 11521108
TI  - [Endoscopic aspect of ulcerated tumor-like gastritis associated with Helicobacter
      heilmannii].
AB  - We report on 5 cases with an endoscopic aspect exceptionally described of
      ulcerated tumor-like gastritis associated with Helicobacter heilmannii. This rare
      but ubiquitary bacteria, belonging to the same family as Helicobacter pylori, is
      epidemiologically and structuraly different. When these endoscopic lesions are
      detected, Helicobacter heilmannii has to be looked for carefully. The treatment,
      which is the same than for Helicobacter pylori, must lead to complete repair of
      endoscopic and histologic lesions.

PMID- 11521109
TI  - [Repetitive acute pancreatitis in a late-diagnosed cystic fibrosis: prevention of
      relapses by octreotide in the long term].
AB  - We report on the case of a 35 year-old woman who was initially admitted for acute
      pancreatitis in october 1995. The patient was suffering from asthma (since
      childhood) and diffuse abdominal pain (since adolescence). The diagnosis of
      cystic fibrosis was made fortuitously during a sterility evaluation. After
      extensive etiological screening the acute pancreatitis was considered to be a
      manifestation of the cystic fibrosis. Despite therapy with pancreatic enzymes,
      the patient continued to suffer from chronic abdominal pain. High intake of
      analgesics was required. Until December 1995, the patient was repeatedly admitted
      for episodes of acute pancreatitis. In January 1996, we initiated a preventive
      treatment with subcutaneous octreotide between 100 and 200 microgram, three time
      a day. Thereafter, there were fewer episodes of pancreatitis and the consumption
      of analgesics decreased. Side effects of octreotide were intermittent diarrhea
      and development of cholelithiasis that was complicated by biliary migration in
      November 1998. In June 1999, the prolonged-release form of the molecule was given
      without modification of the efficacy.

PMID- 11521110
TI  - [Portal vein thrombosis associated with a myeloproliferative disorder,
      prothrombin G20210A mutation, antiphospholipid syndrome, with repermeation during
      anticoagulant therapy].
AB  - Portal vein thrombosis, except in hepatocellular carcinoma and severe cirrhosis,
      is due to one or several prothrombotic disorders with or without a local
      precipitating factor. We report a case of a portal and splenic vein thrombosis,
      without cavernoma and varices which occurred in a 72-year-old man with abdominal
      pain and weakness. Three prothrombotic states including latent myeloproliferative
      disorder, antiphospholipid syndrome, and factor II G202101 mutation, were
      observed. Anticoagulant treatment resulted in complete repermeation of the portal
      and splenic veins without a hemorrhagic event. This illustrates that several
      prothrombotic states may occur in a single patient with portal vein thrombosis.
      Early anticoagulant therapy, in recent portal vein thrombosis, can result in
      repermeation.

PMID- 11521111
TI  - [Cervical osteosynthesis for myelopathy: an unusual cause of dysphagia].

PMID- 11521112
TI  - [Diagnosis of symptom-free celiac disease in a patient with persistent
      hypertransaminasemia of obscur origin].

PMID- 11521113
TI  - [Crohn's disease and poorly-differentiated rectal endocrine tumor].

PMID- 11521114
TI  - [Vigabatrin-induced cytolytic hepatitis].

PMID- 11521115
TI  - [Genetic incidence of Gilbert's syndrome in France].

PMID- 11521116
TI  - Introduction. The hormone continuum: accrual of women's health benefits.

PMID- 11521117
TI  - Current perspectives on oral contraceptive use.
AB  - Oral contraceptives are one of the most highly effective forms of contraception
      and provide many short- and long-term noncontraceptive health benefits. They
      control menstrual cycle irregularities, such as breakthrough bleeding and
      amenorrhea, and are effective in treating dysfunctional uterine bleeding. In
      addition, for decades after oral contraceptive use is discontinued they are
      associated with substantial decreases in the risk of ovarian cancer (up to 80%)
      and of endometrial cancer (40%-50%), and nearly eliminate benign functional
      ovarian cysts. Long-term oral contraceptive use confers protection against benign
      breast disease and colorectal cancer, may help prevent rheumatoid arthritis,
      decreases ectopic pregnancy and hospitalizations for pelvic inflammatory disease,
      and helps preserve bone mineral density to reduce risk of fractures. Large bodies
      of evidence from extensive research have clarified the perceived association of
      oral contraceptive use with cardiovascular disease and with breast cancer.
      Findings indicate that there is no increased risk of myocardial infarction or
      stroke associated with oral contraceptive use in healthy, nonsmoking,
      normotensive women. Although there is a 3- to 4-fold increased risk of venous
      thromboembolism with current oral contraceptive use, the absolute risk is very
      small and is half that associated with pregnancy. Women of all reproductive ages,
      including perimenopausal women, can realize many health benefits through oral
      contraceptive use, including improved health status later in life.

PMID- 11521118
TI  - Current perspectives on benefits and risks of hormone replacement therapy.
AB  - Hormone replacement therapy with estrogen alone or with added progestin relieves
      menopausal symptoms and physical changes associated with depleted endogenous
      estrogen levels. Estrogen replacement has also demonstrated a clear benefit in
      the prevention of osteoporosis. Hormone replacement therapy with added progestin
      maintains spinal bone density, protects against postmenopausal hip fractures, and
      provides these benefits even when therapy is started after age 60. More recently,
      additional benefits have emerged. Current estrogen and hormone replacement
      therapy users have a 34% reduction in the risk of colorectal cancer and a 20% to
      60% reduction in the risk of Alzheimer's disease. Until recently, the body of
      evidence indicated that hormone replacement therapy with estrogen only reduced
      cardiovascular disease risk by 40% to 50% in healthy patients; whether the
      findings of 3 ongoing trials will change this conclusion is pending availability
      of the final results. The many benefits of estrogen and hormone replacement
      therapy must be weighed against a slight increase in the risk of breast cancer
      diagnosis with use for 5 or more years, but which disappears following cessation
      of therapy. Overall, estrogen and hormone replacement therapy improves the
      quality of life and increases life expectancy for most menopausal women.

PMID- 11521119
TI  - Preclinical profiles of progestins used in formulations of oral contraceptives
      and hormone replacement therapy.
AB  - Progestins used in oral contraceptive formulations available in the United States
      include norgestimate, desogestrel, norethindrone, norethindrone acetate, and
      levonorgestrel. Progestins used in the United States in continuous and
      intermittent formulations of hormone replacement therapy are norgestimate,
      medroxyprogesterone acetate, and norethindrone acetate. The chemical structure of
      a progestin determines its relative binding affinity for the progesterone and
      androgen receptors, as well as the sex hormone binding globulin in human serum,
      and determines its clinical profile. Overall, the properties of levonorgestrel or
      norethindrone acetate in this regard differ from norgestimate and are more
      conducive to androgenic stimulation. Estrogen replacement offers cardioprotective
      effects in postmenopausal women. Progestins are added to hormone replacement
      therapy to counteract the well-known increased risk of endometrial hyperplasia
      associated with the use of unopposed estrogen. Animal models show that for some
      parameters, including improvement of lipid profiles, progestins can diminish the
      cardioprotective effect of estrogen. Initial animal studies of norgestimate
      combined with estrogen do not show an attenuation of estrogenic effects.

PMID- 11521120
TI  - Oral contraceptive use in perimenopause.
AB  - Perimenopause represents a transition period lasting about 5 years before the
      permanent cessation of spontaneous menses. During this transition, the emphasis
      of clinical care changes. Although women still need effective contraception
      during perimenopause, issues including loss of bone mineral density, menstrual
      cycle changes, and vasomotor instability also need to be addressed. Hormone
      replacement therapy is not the first-line treatment for women with symptomatic
      perimenopause because hormone replacement therapy neither suppresses ovulation
      nor provides contraception; also, it will not prevent and in fact may aggravate
      unpredictable perimenopausal bleeding. Oral contraceptives offer many benefits
      for healthy, nonsmoking, perimenopausal women. Oral contraceptive use by women in
      their 40s has been found to decrease the risk of postmenopausal hip fractures and
      regularize menses in women with dysfunctional uterine bleeding, reducing the need
      for surgical intervention for benign menstrual conditions. Use of oral
      contraceptives also can reduce long-term risk of endometrial and ovarian cancers.
      There is also good evidence that oral contraceptives relieve vasomotor symptoms
      in perimenopausal women. Oral contraceptives can be viewed as a strategy not only
      to improve perimenopausal symptoms, provide effective contraception, and reduce
      some long-term health risks, but also to enhance the quality of life for
      perimenopausal women.

PMID- 11521121
TI  - Combined oral hormone replacement therapy formulations.
AB  - Today, clinicians are challenged to address a woman's contraceptive needs during
      her reproductive and perimenopausal years and then provide her with a menopausal
      therapeutic option. This option should offer optimal symptom relief,
      noncontraceptive health benefits, and a good tolerability profile. The benefits
      of hormone replacement therapy include control of vasomotor symptoms, reduction
      of vulvovaginal atrophy, and protection against osteoporosis. Research also
      points to emerging hormone replacement therapy benefits such as protection
      against cardiovascular disease, colon cancer, and Alzheimer's disease. One of the
      primary considerations in the transition from oral contraceptive use to hormone
      replacement therapy is the tolerability profile of the progestin component of the
      hormone replacement therapy. Because progestin-related side effects are among the
      main reasons for discontinuation of hormone replacement therapy, the selection of
      a formulation that contains the same well-tolerated progestin as in the woman's
      oral contraceptive can be particularly important to successful use of hormone
      replacement therapy. Currently in the United States continuous combined hormone
      replacement therapy is available in 3 formulations and 1 continuous
      estrogen/intermittent progestin formulation. Although direct comparative trials
      are lacking, available data suggest that the new, continuous 17beta
      estradiol/intermittent norgestimate hormone replacement therapy formulation may
      offer advantages over regimens that contain older progestins with metabolic
      disadvantages.

PMID- 11521122
TI  - Alternatives for women through menopause.
AB  - Today, 42% of Americans use alternative nonprescription therapies to treat
      medical conditions; 46% of nonprescription alternative use for principal medical
      conditions is done without consulting either a medical doctor or a nonphysician
      practitioner of alternative therapy. Many nontraditional alternatives are used to
      treat the hot flashes and somatic complaints of menopause, for which options such
      as hormone replacement therapy and other prescription and over-the-counter drugs
      are also available. To date, no one agent treats all menopausal symptoms as
      effectively as estrogen. Selective estrogen-receptor modulators can help prevent
      osteoporosis but do not relieve menopausal symptoms. However, some women are
      unwilling or unable to take hormone replacement therapy, and some decide to
      discontinue therapy. Evidence supporting the use of some nonprescription
      alternatives for conditions related to menopause is limited. Patients need to be
      aware of the potential for drug interactions when these alternative therapies are
      used concomitantly with prescription drugs. The current evidence to support use
      of hormone replacement therapy, selective estrogen-receptor modulators, and
      nontraditional alternatives is reviewed here.

PMID- 11521123
TI  - Selection of oral contraceptives or hormone replacement therapy: patient
      communication and counseling issues.
AB  - Oral contraceptives and combination hormone replacement therapy are underused by
      most women. Among users, lack of compliance/adherence to oral contraceptive or
      hormone replacement therapy regimens can lead to discontinuation and deprive
      women of the full range of benefits achieved through hormone continuity. To
      prevent unintended pregnancy and to improve the health outcomes of women of all
      ages and the overall quality of life, adherence and continuation rates need to be
      improved for oral contraceptive and hormone replacement therapy use. Effective
      communication and counseling during the oral contraceptive and hormone
      replacement therapy regimen selection process and subsequent follow-up
      interactions are essential. Patients need to be informed in a clear and concise
      manner that, for most women, the benefits of oral contraceptives and hormone
      replacement therapy outweigh any associated health risks. Data should be
      presented without epidemiologic jargon and in terms that are easily understood.
      It is recommended that realistic expectations concerning the possible side
      effects, especially during the initial use of hormones, are established before
      use; furthermore, the selection of a formulation should take into account the
      unique needs of each patient.

PMID- 11521125
TI  - The cardiovascular specialist's role in lifestyle issues.

PMID- 11521127
TI  - Silent killers.

PMID- 11521126
TI  - Implementing hypertension recommendations.

PMID- 11521129
TI  - Myocardial scintigraphy correlates poorly with coronary angiography in the
      screening of transplant arteriosclerosis.
AB  - BACKGROUND: Coronary angiography remains an important screening tool for
      transplant coronary arteriosclerosis (TxCAD) after heart transplantation despite
      criticism that it underestimates the incidence of TxCAD. In an effort to improve
      TxCAD incidence estimation, several methods of screening have been proposed. In
      the present study, the incidence of TxCAD assessed by both yearly coronary
      angiography and stress myocardial scintigraphy imaging was reviewed. PATIENTS AND
      METHODS: Ninety-nine consecutive primary heart transplantations were performed
      from 1988 to 1999. The standard immunosuppression protocol consisted of the
      introduction of antilymphocyte globulin and steroids, while maintenance therapy
      was with cyclosporine, imuran and steroids. Coronary angiography and a stress 2
      methoxyisobutyl-isonitrile perfusion scan were performed yearly. TxCAD was
      defined by angiographic evidence of luminal abnormality by catheterization, or a
      perfusion abnormality at rest or after stress on myocardial scintigraphy.
      RESULTS: The mean recipient age was 49+/-12 years and the mean donor age was 33+/
      13 years. The etiology of heart failure was ischemic cardiomyopathy (50%),
      dilated cardiomyopathy (41%) and congenital heart disease (9%). The freedom from
      angiographic TxCAD was 92% at one year, 64% at five years and 35% at eight years.
      The freedom from nuclear imaging TxCAD was 92% at one year, 69% at five years and
      44% at eight years. However, a diagnosis of TxCAD by angiography only correlated
      with a diagnosis of TxCAD by nuclear imaging 52.8% of the time in the same
      patient, with a median time between studies of one month. CONCLUSION: The overall
      incidence of TxCAD diagnosed by angiography and nuclear imaging appears similar
      but correlates poorly in patients, casting doubt on the routine use of myocardial
      scintigraphy for screening TxCAD.

PMID- 11521128
TI  - A prospective, population-based study of low density lipoprotein particle size as
      a risk factor for ischemic heart disease in men.
AB  - BACKGROUND: The current interpretation of the increased risk of ischemic heart
      disease (IHD) associated with reduced low density lipoprotein (LDL) particle size
      is based entirely on data derived from relatively small case-control studies,
      with a lack of evidence from large, prospective, population-based cohort data.
      OBJECTIVES: To investigate the association between LDL particle size and incident
      IHD on the basis of data from the entire population-based, prospective cohort of
      men from the Quebec Cardiovascular Study. PATIENTS AND METHODS: Analyses were
      conducted in a cohort of 2057 men who were all initially free of IHD, and who
      were followed up over a five-year period, during which 108 first IHD events
      (myocardial infarction, angina or coronary death) were recorded. LDL particle
      size was measured by nondenaturing gradient gel electrophoresis. RESULTS: Cox
      proportional hazards analysis indicated that the relationship between LDL
      particle size and the risk of future IHD events was not linear. Men with an LDL
      particle size less than 256.0 A had a significant 2.2-fold increase in the five
      year rate of IHD (P<0.001) compared with men having an LDL particle size greater
      than 256.0 A. Multivariate and subgroup analyses indicated that small, dense LDL
      particles predicted the rate of IHD independent of LDL cholesterol,
      triglycerides, high density lipoprotein (HDL) cholesterol, apolipoprotein B and
      the total cholesterol to HDL cholesterol ratio. Finally, the magnitude of the
      increase in IHD risk attributed to lipid risk factors was modulated to a
      significant extent by variations in LDL particle size. CONCLUSIONS: The present
      study provides the first large scale, population-based, prospective evidence
      supporting the hypothesis that small, dense LDL particles may be associated with
      an increased risk of IHD. The results also suggest that information on LDL
      diameter may improve the ability to predict IHD risk accurately over traditional
      lipid variables.

PMID- 11521130
TI  - Focal arterial transgene expression after local gene delivery.
AB  - BACKGROUND: Gene therapy for the treatment of vascular disease is limited by a
      low transfection efficiency and/or undesired biological responses. OBJECTIVE: To
      determine the transfection efficiency of delivering a liposome/DNA complex into
      balloon-injured rabbit arteries systematically or using a local delivery
      catheter. METHODS: The cationic liposomes N-[1-(2,3-dioleoyloxy) propyl]-N,N,N
      trimethylammonium methyl-sulphate and dioleoyl-phosphatidylethanolamine were
      mixed 1:1 (wt/wt) and combined with the plasmid pCMV-AP containing the human
      placental alkaline phosphatase (AP) reporter gene. Before initiating the in vivo
      experiments, the optimal ratio of liposome to DNA complex and the persistence of
      transgene expression were determined in cultured vascular smooth muscle cells
      (SMC). In vivo, a Dispatch catheter was used for local delivery of the
      liposome/DNA complex into rabbit iliac arteries that had been balloon injured
      five days previously. The contralateral iliac or renal artery was also balloon
      injured, and liposomes with normal saline were delivered as a negative control.
      For the systemic delivery group, the liposome/DNA complex was delivered through
      an ear vein. RESULTS: AP expression in transfected SMC persisted for 28 days in
      vitro, although the percentage of transfected cells declined with time (eg, at 24
      h it was 27.3%+/-2.9%, at 28 days it was 0.4%+/-0.1%). SMC proliferation in vitro
      enhanced the transfection efficiency 12-fold. In vivo, local delivery resulted in
      low levels of transfection in arteries harvested one day postdelivery; however,
      six of seven arteries harvested three days postdelivery had multiple regions of
      focal transgene expression involving all three arterial layers. For the systemic
      delivery group, two of nine arteries expressed the transgene. No transgene
      expression was found in uninjured arteries in either the local or systemic
      delivery groups. However, with both local and systemic delivery, balloon-injured
      arteries that received liposomes and saline showed low levels of AP expression in
      either the neointima, media or adventitia, presumably due to systemic
      recirculation of the liposome/AP construct. CONCLUSIONS: Liposome-mediated gene
      transfection can be successfully performed to all vessel layers in vivo by using
      a local delivery catheter, and may provide a therapeutic opportunity for
      modulating atherosclerosis and restenosis. Unwanted transfection at a distance
      may occur with catheter-based local delivery and requires further refinement.

PMID- 11521131
TI  - Accelerated glycolysis and greater postischemic dysfunction in hypertrophied rat
      hearts are independent of coronary flow.
AB  - BACKGROUND: After ischemia, glycolysis and dysfunction are greater, while
      coupling of glucose oxidation to glycolysis is lower in hypertrophied hearts than
      in nonhypertrophied hearts. OBJECTIVE: To test the hypothesis that accelerated
      glycolysis, reduced coupling of glucose oxidation to glycolysis and increased
      postischemic dysfunction in hypertrophied hearts compared with nonhypertrophied
      hearts occur in the absence of differences in coronary flow. MATERIALS AND
      METHODS: Function, glycolysis and glucose oxidation were measured in isolated
      working control and hypertrophied rat hearts studied for 30 min before, and for
      40 min after no flow global ischemia for 20 min under conditions in which
      coronary flow was comparable between the two groups. The hearts were perfused
      with 1.2 mmol/L palmitate, 5.5 mmol/L [5-3H/U-14C]-glucose, 0.5 mmol/L lactate,
      100 mU/L insulin at a preload of 11.5 mmHg, and an afterload of 60 mmHg in
      control hearts or 80 mmHg in hypertrophied hearts. RESULTS: Despite comparable
      rates of coronary flow, functional recovery was lower in hypertrophied hearts
      than in control hearts. The rates of glycolysis were accelerated in hypertrophied
      hearts, while glucose oxidation did not significantly differ between the two
      groups. As a result, the coupling of glucose oxidation to glycolysis was lower in
      hypertrophied hearts than in control hearts. CONCLUSIONS: Increased postischemic
      dysfunction, accelerated glycolysis and reduced coupling of glucose oxidation to
      glycolysis in hypertrophied hearts compared with control hearts cannot be
      accounted for by differences in coronary flow. These data provide support for the
      concept that alterations in glucose metabolism contribute to the exaggerated
      postischemic dysfunction of hypertrophied hearts.

PMID- 11521133
TI  - World congress in Winnipeg.

PMID- 11521132
TI  - Atrial myxoma presenting as isolated unilateral blindness: a case report and
      review of the literature.
AB  - Myxomas are the most common primary cardiac tumours in adults. Systemic
      embolization is often the first presentation, with the central nervous system
      being the most common site. The present report reviews the literature and
      discusses a 29-year-old patient who presented with an isolated left retinal
      artery occlusion secondary to a previously undiagnosed left atrial myxoma.

PMID- 11521134
TI  - Smoggy days are here again.

PMID- 11521135
TI  - A need to improve communications between the Canadian Thoracic Society and its
      members.

PMID- 11521136
TI  - Youthful inspiration.

PMID- 11521137
TI  - Eighteen month follow-up of arterial blood gases in patients with chronic
      obstructive pulmonary disease.

PMID- 11521138
TI  - Influence of bulla volume on postbullectomy outcome.
AB  - OBJECTIVE: To quantify the contribution of the resected volume and the presence
      of associated, functionally significant emphysema to the postoperative
      improvement of pulmonary function after resection of giant lung bullae. DESIGN:
      Patients undergoing elective surgery for giant bullae who had had complete
      pulmonary function and radiographic studies performed were reviewed
      retrospectively. SETTING: All 25 patients underwent surgery at the thoracic
      surgery unit of the University of Pisa, Pisa, Italy. METHODS: Pulmonary function
      was assessed before and 12 months after surgery. On the chest radiograph, the
      location of bullae, and the signs of compression and emphysema were evaluated.
      The radiographic total lung capacity (TLC(x-ray)) and the volume of bullae were
      measured according to the ellipse method. Postoperatively, functional and
      radiographic changes were analyzed. The percentage change in forced expiratory
      volume in 1 s (Delta FEV(1)%) after surgery was the main outcome measure. The
      influence of factors related to emphysema and bulla volume on the functional
      improvement postbullectomy was assessed by stepwise multiple regression. RESULTS:
      Before surgery, the TLC(x-ray) overestimated the TLC measured by nitrogen
      washout, with a mean difference between the two measurements of 1.095 L. A close
      relationship was found between the TLC(x-ray) and the plethysmographic TLC (n=6;
      r=0.95). After surgery, dyspnea lessened (P<0.05) and FEV(1) increased (P<0.01).
      Statistically, the radiographic bulla volume was the single most important factor
      determining the Delta FEV(1)% (r=0.80, P<0.0001). CONCLUSIONS: These findings
      suggest that the preoperative size of bullae is the most important contributor to
      the improvement in ventilatory capacity after bullectomy, and that it is possible
      to predict the expected increase of postoperative FEV(1) from preoperative bulla
      volume.

PMID- 11521139
TI  - Sputum cell counts and exhaled nitric oxide in patients with gastroesophageal
      reflux, and cough or asthma.
AB  - BACKGROUND: Gastroesophageal reflux (GER) is commonly associated with chronic
      cough and asthma, but there is little or no information on the nature of any
      associated airway inflammation. OBJECTIVE: To observe whether the association
      with GER worsens airway inflammation in patients with chronic cough or asthma.
      PATIENTS AND METHODS: The airway inflammatory indexes in induced sputum and
      exhaled air were examined in a cross-sectional study of 11 patients with cough
      and GER, nine patients with mildly symptomatic asthma and GER, nine patients with
      mildly symptomatic asthma without GER and nine normal, healthy control subjects.
      GER was shown objectively by 24 h ambulatory pH recording. RESULTS: The sputum
      total cell count, the proportion of neutrophils and macrophages, and the
      fibrinogen level were normal in all four groups, with no significant differences
      among the groups. The sputum eosinophil and metachromatic cell percentages, and
      eosinophil cationic protein levels were normal in patients with cough and GER.
      They were significantly increased in patients with asthma compared with healthy
      subjects (P<0.01) and patients with cough (P<0.01), but were not different
      between groups with and without GER. Exhaled nitric oxide levels showed similar
      results (P<0.01). The correlations between the number of episodes of reflux and
      the proportion of sputum eosinophils, neutrophils or exhaled nitric oxide were
      modest but not significant. CONCLUSIONS: GER, when associated with cough or
      mildly symptomatic asthma, does not cause or aggravate existing airway
      inflammation as measured by induced sputum cell counts and fibrinogen level, or
      by exhaled nitric oxide.

PMID- 11521140
TI  - Spirometric predictors for the exclusion of severe hypoxemia in chronic
      obstructive pulmonary disease.
AB  - BACKGROUND: Controversy has existed over the need for routine arterial blood gas
      (ABG) analysis in patients with chronic obstructive pulmonary disease (COPD).
      Some authors recommend it in all patients with COPD, but others find it
      unnecessary if the forced expiratory volume in 1 s (FEV(1)) is 50% of predicted
      or greater. OBJECTIVES: To clarify this controversy, and to investigate
      correlations between severe hypoxemia and multiple spirometric parameters in
      patients with COPD with FEV(1) 50% of predicted or greater. PATIENTS AND METHODS:
      In 103 consecutive patients with COPD with FEV(1) 50% of predicted or greater,
      and without any other cardiopulmonary disorder, the incidence of severe hypoxemia
      (partial pressure of arterial oxygen less than 60 mmHg) was established by ABG
      analysis. Positive and negative predictive values (PPVs and NPVs, respectively)
      for severe hypoxemia for multiple spirometric parameters (FEV(1), FEV(1)/forced
      vital capacity [FVC], peak expiratory flow [PEF], maximal midexpiratory flow rate
      [FEF(25-75)]) were evaluated in a stepwise manner. RESULTS: Twenty-two patients
      (21%) were found to be severely hypoxemic. In the severely hypoxemic group, the
      mean values for FEV(1), FEV(1)/FVC, PEF and FEF(25-75) were 59.0+/-8.19%, 53.6+/
      11.3, 50.6+/-9.3 and 34.4+/-14.2% of predicted, respectively. The mean values for
      the same parameters in the other patients were 58.0+/-4.6%, 52.7+/-7.8, 51.5+/
      7.5 and 39.1+/-7.7% of predicted, respectively. Comparing these parameters
      between the two groups, only the difference in FEF(25-75) was statistically
      significant (P<0.01). Valid PPVs and NPVs could not be established for any of the
      parameters at any level, except for the NPV for FEF(25-75) 50% of predicted or
      greater, which was 92%. This threshold value resulted in a false negative finding
      in less than 5% of the patients with hypoxemia. CONCLUSIONS: The results of the
      present study showed that one in five patients with COPD with FEV(1) 50% of
      predicted or greater was severely hypoxemic. In such patients, hypoxemia may be
      excluded, and ABG analysis may not be needed when the FEF(25-75) is also 50% of
      predicted or greater. The FEV(1), FEV(1)/FVC and PEF parameters failed to predict
      or exclude severe hypoxemia.

PMID- 11521141
TI  - The use of guidelines for the empirical treatment of hospital-acquired pneumonia.
AB  - BACKGROUND: Several practice guidelines for the empirical antimicrobial treatment
      of hospital-acquired pneumonia (HAP) have been developed, but the acceptance and
      use of such guidelines are unknown. OBJECTIVE: To assess physicians' use of
      empirical HAP guidelines published by the American Thoracic Society (ATS) and by
      The University Health Network, Toronto, Ontario. DESIGN: A retrospective assembly
      and chart review. SETTING: A university teaching hospital. PATIENTS: One hundred
      fifteen consecutive patients who had been diagnosed with pneumonia more than 48 h
      after admission to hospital over a 10-month period. RESULTS: The charts of 115
      patients were reviewed. Seventy-five patients (65%) were treated empirically.
      Forty patients (35%) were treated based on microbiological data that were
      available before the initiation of antibiotics. Patients who received
      nonempirical treatment for HAP had a significantly greater acuity of illness than
      the empirically treated group. Thirty-seven patients (49%) who received empirical
      therapy were treated according to either ATS or hospital guidelines for HAP. The
      use of guideline-concordant antimicrobial therapy had no measurable effect on in
      hospital mortality (eight of 37 patients [21.6%] versus seven of 38 patients
      [18.4%], P=0.96) or median length of stay (19 days versus 21 days, P=0.30).
      Patients whose treatment did not follow guideline recommendations tended to
      receive appropriate antimicrobial coverage more often than did those patients
      whose treatment was guideline concordant (15 of 18 patients [83%] versus six of
      11 patients [55%], P=0.49). CONCLUSIONS: Institutional and ATS guidelines for the
      empirical treatment of HAP are less widely used than would be predicted by chance
      at The University Health Network. The clinical utility of these guidelines
      remains to be proven.

PMID- 11521142
TI  - The impact of a nationally coordinated pharmacy-based asthma education
      intervention.
AB  - OBJECTIVE: To assess the impact of a nationally coordinated pharmacy-based
      educational intervention on self-management behaviour and markers of asthma
      control in self-referred patients with asthma. DESIGN: An asthma clinic day was
      set up by a national chain of community pharmacies whereby pharmacists used a
      structured questionnaire to assess asthma control and self-care among self
      referred patients with doctor-diagnosed asthma. In a one-on-one counselling
      session, each patient's educational needs were identified and the appropriate
      education offered. A telephone follow-up 30 days later assessed the impact of
      teaching. SETTING: Community pharmacies across Canada. OUTCOME MEASURES: The
      follow-up questionnaire quantified the number of wheezing episodes or other
      symptoms per week, the number of night-time awakenings per week, and the
      frequency of use of reliever and preventive medications. RESULTS: Of 4080
      patients assessed, 22.2% used an inadequate inhaler technique, 16.4% used a short
      acting beta2-agonist excessively and 21.0% were not using an inhaled
      corticosteroid daily despite a frequency of symptoms that would suggest that it
      was needed. Common educational interventions included a review of inhaler
      technique (41.9%), a recommendation for regular inhaled corticosteroids (31.5%)
      and a referral to the primary care physician (21.0%). Thirty days after the
      educational intervention, patients reported significant decreases in the
      frequency of daytime asthma symptoms, the frequency of nocturnal symptoms and the
      frequency with which short acting beta2-agonists were used, while reporting
      significant increases in their use of preventive medication. CONCLUSIONS: A brief
      assessment and an educational intervention in the community pharmacy can produce
      significant short term improvements in patient-reported symptom control and
      appropriate self-management behaviour.

PMID- 11521143
TI  - Multum in parvo: explorations with a small bag of carbon dioxide.
AB  - A collection of 12 papers published between 1957 and 1972 are revisited. The
      papers had a common theme of the use of rebreathing carbon dioxide and explored a
      variety of topics in respiratory physiology. The first study established a method
      for the noninvasive and indirect estimation of arterial carbon dioxide pressure
      that was suitable for the routine clinical monitoring of respiratory failure and
      whose clinical utility remains to this day, but which also provided observations
      that were the stimulus for the studies that followed. The rate of rise in the
      partial pressure of carbon dioxide (PCO(2)) during rebreathing led to an analysis
      of body carbon dioxide storage capacity. Knowledge of carbon dioxide storage led
      to a method for quantifying lactate production in exercise without the need for
      blood sampling. The changes in ventilation that accompanied the increase in
      PCO(2) provided the basis for a rapid method for measuring aspects of breathing
      control (Read's method), which was later modified to measure the ventilatory
      response to hypoxia. The physiology of breath-holding was explored through
      observations of the fall in breath-holding time as PCO(2) climbed. Rebreathing
      also allowed increases in voluntary ventilation to be achieved without the
      development of alkalosis, leading to studies of maximal voluntary ventilation and
      respiratory muscle fatigue. Equilibration of PCO(2) during rebreathing was used
      to measure mixed venous PCO(2) during exercise and develop an integrated approach
      to the physiology of exercise in health and disease; alveolar-arterial
      disequilibrium in PCO(2) during exercise was uncovered. Equilibration of PCO(2),
      as well as PO(2), during rebreathing of carbon dioxide and nitrogen gas mixtures
      showed different time courses of venous gases at the onset of exercise. Starting
      with the rebreathing of carbon dioxide in oxygen mixtures in a small rubber bag,
      an astonishing range of topics in respiratory physiology was explored, with
      observations that remain valid, but in some respects unresolved, to the present
      day.

PMID- 11521144
TI  - Respiratory failure associated with the lipodystrophy syndrome in an HIV-positive
      patient with compromised lung function.
AB  - Protease inhibitors, used as treatment in human immunodeficiency virus (HIV)
      infection, are associated with a syndrome of peripheral lipodystrophy, central
      adiposity, hyperlipidemia and insulin resistance. An HIV-positive patient with
      chronic obstructive pulmonary disease is presented who developed the
      lipodystrophy syndrome that is associated with the use of protease inhibitors. It
      is postulated that the lipodystrophy syndrome further compromised his lung
      function, leading to respiratory failure. Patients who have pulmonary disease and
      are taking protease inhibitors require monitoring of clinical status and
      pulmonary function tests.

PMID- 11521145
TI  - Right atrial perforation secondary to implantable cardioverter defibrillator
      insertion.
AB  - Implantable cardioverter defibrillator (ICD) placements can be associated with
      serious complications. This paper reports a patient in whom percutaneous
      placement of an ICD resulted in a hemopneumothorax. This was due to an active
      fixation lead that perforated the right atrial wall and injured the adjacent lung
      parenchyma. The hemothorax was drained thoracoscopically, and the atrial injury
      was covered with fibrin glue.

PMID- 11521146
TI  - Representation of the visual field in the lateral intraparietal area of macaque
      monkeys: a quantitative receptive field analysis.
AB  - The representation of the visual field in the primate lateral intraparietal area
      (LIP) was examined, using a rapid, computer-driven receptive field (RF) mapping
      procedure. RF characteristics of single LIP neurons could thus be measured
      repeatedly under different behavioral conditions. Here we report data obtained
      using a standard ocular fixation task during which the animals were required to
      monitor small changes in color of the fixated target. In a first step,
      statistical analyses were conducted in order to establish the experimental limits
      of the mapping procedure on 171 LIP neurons recorded from three hemispheres of
      two macaque monkeys. The characteristics of the receptive fields of LIP neurons
      were analyzed at the single cell and at the population level. Although for many
      neurons the assumption of a simple two-dimensional gaussian profile with a
      central area of maximal excitability at the center and progressively decreasing
      response strength at the periphery can represent relatively accurately the
      spatial structure of the RF, about 19% of the cells had a markedly asymmetrical
      shape. At the population level, we observed, in agreement with prior studies, a
      systematic relation between RF size and eccentricity. However, we also found a
      more accentuated overrepresentation of the central visual field than had been
      previously reported and no marked differences between the upper and lower visual
      representation of space. This observation correlates with an extension of the
      definition of LIP from the posterior third of the lateral intraparietal sulcus to
      most of the middle and posterior thirds. Detailed histological analyses of the
      recorded hemispheres suggest that there exists, in this newly defined unitary
      functional cortical area, a coarse but systematic topographical organization in
      area LIP that supports the distinction between its dorsal and ventral regions,
      LIPd and LIPv, respectively. Paralleling the physiological data, the central
      visual field is mostly represented in the middle dorsal region and the visual
      periphery more ventral and posterior. An anteroposterior gradient from the lower
      to the upper visual field representations can also be identified. In conclusion,
      this study provides the basis for a reliable mapping method in awake monkeys and
      a reference for the organization of the properties of the visual space
      representation in an area LIP extended with respect to the previously described
      LIP and showing a relative emphasis of central visual field.

PMID- 11521147
TI  - Frequency response areas of neurons in the mouse inferior colliculus. I.
      Threshold and tuning characteristics.
AB  - Excitatory and inhibitory frequency response areas of 130 neurons of the central
      nucleus of the mouse inferior colliculus (ICC) were mapped by extracellular
      single-unit recordings and quantitatively evaluated with regard to thresholds,
      steepness of slopes of excitatory tuning, characteristic frequencies of
      excitation (CF(E)), inhibition (CFI), and bandwidths of response areas (sharpness
      of tuning). Two-tone stimuli were used to determine the shapes of inhibitory
      response areas. Class I neurons (n=54) had asymmetrical (with regard to the
      CF(E)) excitatory and inhibitory response areas, with inhibition above CF(E)
      having lower thresholds and covering larger areas than inhibition below CF(E).
      Quantitative relationships between CF(E) and CF(I) thresholds, and sharpness of
      tuning showed that the receptive fields of about two-thirds of these neurons had
      properties similar to auditory nerve fibers. Class II neurons (n=36) had small
      symmetrical or tilted excitatory areas of rather constant bandwidths and broad
      inhibitory areas reaching far into and often through the excitatory area, leading
      to closed excitatory areas in ten neurons. Class III neurons (n=32) had higher
      excitatory thresholds and the highest proportions of unilateral inhibitory areas
      compared with neurons of the other classes. Their excitatory area often widened
      symmetrically with increasing sound level. Their inhibitory areas did not overlap
      with the excitatory area. Class IV neurons (n=8) had two branches of excitatory
      areas (two-CFs(E)) and six of the neurons had a central inhibitory area in
      addition to the low- and high-frequency inhibitory areas. In most neurons, the
      shapes of excitatory response areas predicted the shapes of inhibitory areas.
      Altogether, 15 neurons from all 4 classes had areas of facilitation in addition
      to inhibitory areas. Facilitation in six class IV neurons occurred between the
      two branches of the excitatory area. All 130 neurons had large inhibitory areas,
      106 of them on both sides of the excitatory area. That is, sound processing in
      the ICC shows strong inhibitory components. The close relationships between
      excitatory and inhibitory CFs found here indicate that inhibitory projections to
      and interactions within the ICC are tonotopically organized comparable to the
      excitatory ones.

PMID- 11521148
TI  - Cerebellar unipolar brush cells are targets of primary vestibular afferents: an
      experimental study in the gerbil.
AB  - The unipolar brush cell (UBC) is an excitatory glutamatergic interneuron,
      situated in the cerebellar granular layer, that itself receives excitatory
      synaptic input on its dendritic brush from a single mossy fiber terminal in the
      form of a giant glutamatergic synapse. The UBC axon branches within the granular
      layer, giving rise to large terminals that synapse with both granule cell and UBC
      dendrites within glomeruli and resemble in morphological and functional terms
      those formed by extrinsic mossy fibers. So far, the only demonstrated extrinsic
      afferents to the UBC are the choline acetyltransferase (ChAT)-positive mossy
      fibers, some of which originate from the medial and descending vestibular nuclei.
      To ascertain whether UBCs are innervated by primary vestibular fibers, we
      performed a tract-tracing light and electron microscopic study of the
      vestibulocerebellum in gerbils. Macular and canal vestibular end-organs were
      individually labeled by injection of biotinylated dextran amine. After an
      appropriate survival time, gerbils were then processed for light and electron
      microscopic analysis of central vestibular projections. In the nodulus and uvula,
      labeled primary vestibular fibers formed mossy terminals synapsing with both
      granule cells and UBCs in all of the injected gerbils. Thus, innervation of UBCs
      by extrinsic mossy fibers carrying static and dynamic vestibular signals
      represents the first synapse of networks that contribute a powerful form of
      distributed excitation in the granular layer.

PMID- 11521149
TI  - Relationship between cocontraction, movement kinematics and phasic muscle
      activity in single-joint arm movement.
AB  - Patterns of muscle coactivation provide a window into mechanisms of limb
      stabilization. In the present paper we have examined muscle coactivation in
      single-joint elbow and single-joint shoulder movements and explored its
      relationship to movement velocity and amplitude, as well as phasic muscle
      activation patterns. Movements were produced at several speeds and different
      amplitudes, and muscle activity and movement kinematics were recorded. Tonic
      levels of electromyographic (EMG) activity following movement provided a measure
      of muscle cocontraction. It was found that coactivation following movement
      increased with maximum joint velocity at each of two amplitudes. Phasic EMG
      activity in agonist and antagonist muscles showed a similar correlation that was
      observable even during the first 30 ms of muscle activation. All subjects but one
      showed statistically significant correlations on a trial-by-trial basis between
      tonic and phasic activity levels, including the phasic activity measure taken at
      the initiation of movement. Our findings provide direct evidence that muscle
      coactivation varies with movement velocity. The data also suggest that
      cocontraction is linked in a simple manner to phasic muscle activity. The
      similarity in the patterns of tonic and phasic activation suggests that the
      nervous system may use a simple strategy to adjust coactivation and presumably
      limb impedance in association with changes in movement speed. Moreover, since the
      pattern of tonic activity varies with the first 30 ms of phasic activity, the
      control of cocontraction may be established prior to movement onset.

PMID- 11521150
TI  - Neural activity correlated with the preparation and execution of visually guided
      arm movements in the cingulate motor area of the monkey.
AB  - Recent anatomical and physiological studies have suggested that parts of the
      cingulate cortex are involved in the control of movement. These areas have been
      collectively termed the cingulate motor area (CMA). Currently almost nothing is
      known, however, about how neurons in the CMA actually participate in the control
      of movement. Therefore, we investigated the role of cells in the dorsal and
      ventral banks of the CMA (CMAd and CMAv, respectively) in the preparation and
      execution of visually guided arm movements. We recorded the activity of neurons
      while a monkey performed a visually guided, two-dimensional instructed delay
      task. A monkey was required to operate a joystick that moved a cursor from a
      centrally located hold target to one of four peripheral targets. Neurons were
      classified as exhibiting preparatory activity if the neural discharge during the
      postinstruction delay period was significantly higher than the preinstruction
      activity. Neurons were classified as exhibiting movement activity if the neural
      discharge was significantly elevated around the time of the movement. Of the 115
      task-related neurons studied, 18 (16%) exhibited only preparatory activity, 48
      (42%) exhibited only movement activity, and 49 (43%) exhibited both preparatory
      and movement activity. Neurons were further classified in terms of their
      directional tuning. For 51% of neurons with preparatory activity, that activity
      was directional. A significantly larger proportion of movement-related activity
      was directional (78%). For neurons with both directional preparatory and movement
      activity, the preferred directions were highly correlated (r=0.83). The median
      onset of movement activity was 10 ms before the beginning of movement (range -200
      to 200 ms). The patterns and directionality of task-related activity of CMA
      neurons observed in this study are similar to those previously reported for other
      cortical motor areas. Together, these data provide preliminary evidence that
      neurons in CMAd and CMAv play a role in both the preparation and execution of
      visually guided arm movements.

PMID- 11521151
TI  - Patients with the major and minor form of hyperekplexia differ with regards to
      disynaptic reciprocal inhibition between ankle flexor and extensor muscles.
AB  - The aim of the present study was to investigate the contribution of reciprocal
      inhibition to muscle tone by examining the transmission in the reciprocal
      inhibitory pathway in patients with a known defect in the glycine receptor. The
      study was performed in eight patients with hereditary hyperekplexia, six with the
      major form and two with the minor form of the disease. A mutation in the alpha1
      subunit of the glycine receptor had been demonstrated in the patients with the
      major form, whereas no mutation was seen in the patients with the minor form.
      Disynaptic reciprocal inhibition, which is presumed to be mediated by glycine,
      was not seen in the patients with the major form of the disease, while it could
      be evoked in the patients with the minor form of the disease. Presynaptic
      inhibition, which is presumed to be mediated by GABA, was seen in both types of
      patients. It is concluded that the major form of hereditary hyperekplexia is
      associated with impaired transmission in glycinergic reciprocal inhibitory
      pathways. The findings demonstrate the importance of reciprocal inhibition for
      the muscle tone in man, and it is suggested that the impaired reciprocal
      inhibition seen in patients with a defect in the glycine receptor may contribute
      to the increased muscle stiffness that is observed in these patients.

PMID- 11521152
TI  - Effects of intrathecal c-fos antisense oligodeoxynucleotide on adjuvant-induced
      thermal hyperalgesia.
AB  - We examined the effects of intrathecally preadministered injections of a
      phosphorothioate analog of c-fos antisense and mismatch oligodeoxynucleotides
      (ODNs) on the withdrawal latency to a thermal stimulus following unilateral
      injection of complete Freund's adjuvant (CFA) into the hind footpad of rats.
      Pretreatment with the c-fos antisense ODN significantly decreased the CFA-induced
      expression of c-Fos protein dose-dependently in ipsilateral laminae I/II (LI/II)
      of the dorsal horn (mean +/- SEM per section: 10 nM ODN, 43.9+/-1.3; 25 nM ODN,
      19.4+/-4.1) compared with pretreatment with the mismatch ODN (63.6+/-2.9; 60.6+/
      4.0) or saline (56.6+/-5.5). Animals pre-treated with 25 nM of the c-fos
      antisense ODN significantly increased the withdrawal latency to the noxious
      thermal stimulation (63.0-70.5%; compared with contralateral to the CFA
      injection) compared with animals pretreated with mismatch ODN (28.5-42.6%) or
      saline (26.4-45.3%) from 0 to 5 h after unilateral injection of CFA into the hind
      footpad. Pretreatment with 10 nM antisense ODN had a less significant effect.
      These results indicate that the expression of CFA-induced c-Fos in the dorsal
      horn might facilitate thermal nociception.

PMID- 11521153
TI  - Two-dimensional sound-localization behavior of early-blind humans.
AB  - To investigate whether the visual system is crucial for adequate calibration of
      acoustic localization cues, sound-localization performance of early blind humans
      was compared with that of sighted controls. Because a potential benefit of vision
      is mainly expected for targets within the two-dimensional (2D) frontal hemifield,
      localization was tested within this target range, while using sounds of various
      durations and spectral content. Subjects were instructed to point, in separate
      experimental sessions, either with their left arm, or with their nose, in the
      direction of the perceived target position as accurately as possible. The
      experiments required the use of all available sound-localization cues such as
      interaural differences in phase and intensity, as well as the complex spectral
      shape cues provided by the pinnae. In addition, for long-duration stimuli,
      subjects could have had access to head motion-induced acoustic feedback.
      Moreover, the two pointing methods allowed us to assess different response
      strategies for the two groups. In an additional series, subjects were instructed
      to respond as quickly as possible. The results show that, in general, 2D sound
      localization performance of blind subjects was indistinguishable from that of
      sighted subjects, both for broad-band noise and for pure tones. In the fast head
      pointing task, the latency distributions of both groups were equal. These
      findings suggest that visual feedback is not required to calibrate the available
      localization cues--including the idiosyncratic and complex spectral shape cues
      for elevation. Instead, the localization abilities of blind people show that the
      putative supervising role of vision may be supported, or taken over, by other non
      visual feedback systems. The results do not provide support for the hypothesis
      that blind people can hypercompensate for the loss of vision in the frontal
      hemifield by developing superior sound-localization abilities. Despite the
      general correspondence in localization behavior, some specific differences
      related to pointing strategies as well as to those between blind and sighted
      subjects were apparent. Most importantly, the reconstructed origin (bias) of arm
      pointing was located near the shoulder for the blind subjects, whereas it was
      shifted and located near the cyclopean eye for the sighted subjects. The results
      indicate that both early blind and sighted humans adequately transform the head
      centered acoustic target coordinates into the required reference frame of either
      motor system, but that the adopted response strategy may be specific to the
      subject group and pointer method.

PMID- 11521154
TI  - Effects of head immobilization on the coordination and control of head and body
      reorientation and translation during steering.
AB  - Changing the direction of locomotion involves lateral translation of the body in
      addition to body reorientation to align with the new travel direction. We
      designed this study to investigate the CNS control of these postural adjustments.
      The specific aims of the study were: first, to test the hypothesis that
      anticipatory head movements towards the new travel path are proactively
      controlled by the CNS to provide a stable frame of reference for body
      reorientation and, second, to investigate the relative contribution of foot
      placement and other mechanisms to the control of lateral body translation during
      steering. We achieved these aims by carrying out a comprehensive biomechanical
      analysis of participants performing a steering paradigm and observing the effects
      of immobilizing the head (by fixing it to the trunk) on postural control and the
      sequencing of body segment reorientation. Participants performed a task whereby
      they were visually cued to change their direction of walking by 30 degrees or 60
      degrees, left or right, at the midpoint of a 9-m path. The temporal sequence of
      body reorientation was consistent with previous findings that the head starts to
      turn in the direction of travel before the rest of the body. Translation of the
      centre of mass (COM) in the new travel direction was achieved both through
      alternate placement of the contralateral foot prior to the turn step and use of a
      hip strategy to control the body pendulum during swing. Immobilizing the head
      resulted in the following significant changes: earlier onset of trunk yaw with
      respect to cue delivery, later trunk roll onset and a reduction in trunk roll
      amplitude. These results provide valuable information regarding the biomechanics
      of steering and support the hypothesis that aligning the head with motor or
      locomotor goals using vision provides the CNS with a stable frame of reference,
      independent of gaze, that can be used to control the repositioning of the body in
      space.

PMID- 11521155
TI  - Anticipatory responses of dopamine neurons and cortical neurons reproduced by
      internal model.
AB  - Animals seem to learn and use internal models; they learn to anticipate
      predictable events, and their behavior in the sensory preconditioning paradigm
      reflects formation of novel associative chains. To investigate possible neural
      correlates, the temporal difference model (TD model) was extended to an internal
      model approach. The proposed model learns reward prediction error signals that
      resemble dopamine neuron activity. In contrast to the original TD model, the
      reward prediction error signals of the proposed model are influenced by the
      formation of novel associative chains in the sensory preconditioning experiment.
      This is consistent with experimental findings, as striatal dopamine concentration
      is influenced by the formation of novel associative chains in this paradigm.
      Comparison of the model architecture with biological neural networks suggests
      that chains of neurons with tonic anticipatory activity may underlie the
      formation of novel associative chains. These findings suggest that dopamine
      neuron activity may reflect the processing of an internal model.

PMID- 11521156
TI  - Experience-dependent modulation of motor corticospinal excitability during action
      observation.
AB  - The primate premotor cortex is endowed with an "action observation/execution
      matching system", that is, the same premotor neurons discharge when actions are
      performed and when actions are observed. Hence, this system predicts a strong
      visual input to the motor system. Whether this input is dependent on visual
      experience or not has not been previously investigated. To address this issue we
      compared corticospinal excitability while subjects viewed frequently observed and
      less frequently observed hand actions of others and of themselves. Motor
      corticospinal excitability was larger when the action orientations were as they
      are frequently observed (Self-away, subject's own hand facing out from the
      subject, or Other-toward, an unknown hand facing toward the subject) compared
      with less frequently observed actions (Self-toward, subject's own hand facing
      "toward" the subject, or Other-away, an unknown hand facing out from the
      subject). This finding suggests that the modulation of motor corticospinal
      excitability during action observation and hence the "action
      observation/execution matching system" is largely dependent upon visual
      experience.

PMID- 11521157
TI  - Local lateral connectivity of inhibitory clutch cells in layer 4 of cat visual
      cortex (area 17).
AB  - To characterise spatially a major component of the anatomical basis of local
      lateral inhibition in layer 4 of cat visual cortex (area 17), we analysed the
      lateral distribution of neuronal somata postsynaptic to electrophysiologically
      characterised GABAergic clutch (basket) cell axons (CC1 and CC2). We report two
      main results. First, the clutch cell axons appear to show isotropic lateral
      connectivity near their cell body (less than 50 microm radius), but beyond this
      core region they show anisotropic lateral connectivity, preferring particular
      angular sectors around their cell body. Second, we estimated the probability of
      lateral connection for each axon arbor as a function of radial distance from the
      parent soma. We found that this radial function has a brief rising phase, to a
      peak at 30-45 microm, and a longer, exponential decaying phase, with a space
      constant of around 50 microm. The shape of the radial connection probability
      function suggests that most lateral inhibitory connections of clutch cells are
      formed with neurons in nearest-neighbour cortical columns. Taken together, the
      results suggest that these individual layer-4 clutch cell axons may inhibit all
      (isotropic) nearest-neighbour cortical columns with a relatively high probability
      of connection, but outside this core region may provide a type of anisotropic
      lateral inhibition of cortical columns with a radially decreasing probability of
      connection.

PMID- 11521159
TI  - Decrease in the Ca2+-activated K+ current of pulmonary arterial smooth muscle in
      pulmonary hypertension rats.
AB  - Pulmonary hypertension exhibits acute elevation of vascular tone and
      hyperreactivity of pulmonary vasculature, which are closely related to patient
      mortality. In the present study, we investigated the characteristics of membrane
      currents of isolated pulmonary artery smooth muscle cells taken from rats with
      monocrotaline-induced pulmonary hypertension. Male Wistar rats were given a
      single subcutaneous injection of monocrotaline or saline, and then sacrificed
      between 18 to 21 days after the injection. The membrane currents in the smooth
      muscle cells from both groups of rats were compared using the whole-cell patch
      clamp technique. With 0.1 mM EGTA in the pipette, the densities of outward
      currents in monocrotaline-injected rats were smaller than those in control rats.
      When EGTA in patch pipettes was increased to 10 mM, the densities of the outward
      currents in monocrotaline-injected rats were equal to those of control rats. The
      Ca2+-activated K+ channel blockers (TEA, iberiotoxin) and nisoldipine were less
      effective on the outward currents of monocrotaline-injected rats. In the current
      clamp mode, a depolarization of membrane potential induced by 4-aminopyridine was
      greater in monocrotaline-injected rats than in control rats because of the
      reduced activity of the Ca2+-activated K+ channels. The Ca2+-activated K+
      channels were decreased in pulmonary hypertension. The reduced activity of the
      currents may be related to the vascular hyperreactivity in pulmonary
      hypertension.

PMID- 11521160
TI  - Evidence for a peripheral mechanism in cardiac opioid withdrawal.
AB  - Studies involving heart catecholaminergic systems in morphine-dependent rats have
      not established whether the adaptive changes observed in the heart during
      morphine withdrawal are mediated peripherally or centrally. In this study,
      naloxone (Nx), naloxone methiodide (NxM) and N-methyl levallorphan (NML),
      quaternary derivatives of Nx and levallorphan, respectively, that do not cross
      the blood-brain barrier, were administered to morphine-dependent rats and
      catecholamines and their metabolites determined in the right ventricle. Rats were
      made dependent on morphine by implantation of morphine pellets for 7 days. On day
      8 animals received s.c. injections of saline, Nx (1 mg/kg), NxM (5 mg/kg) or NML
      (5 mg/kg) and were decapitated 30 min later. Noradrenaline (NA) and its
      metabolites normetanephrine (NMN) and 3-methoxy-4-hydroxyphenylethyleneglycol
      (MHPG) and dopamine (DA) and its metabolite 3,4-dihydroxyphenylacetic acid
      (DOPAC) were determined by high-performance liquid chromatography with
      electrochemical detection. After NxM or NML administration to morphine-dependent
      rats there was a pronounced increase in NMN and DOPAC levels, as well as in NA
      and DA turnovers (as estimated by NMN/NA and DOPAC/DA ratios, respectively) in
      the right ventricle. Similarly, giving Nx to morphine-dependent rats increased
      NMN and DOPAC levels and NA and DA turnovers. In addition, in the paraventricular
      nucleus of the hypothalamus (PVN) NA and DA turnover, measured as the MHPG/NA or
      DOPAC/DA ratios, increased after Nx administration but not after NxM or NML These
      results suggest that the changes in cardiac sympathetic activity observed during
      morphine withdrawal are due to intrinsic mechanisms outside the central nervous
      system. These data may be important for understanding the adaptive changes
      induced in the heart in subjects dependent on opioids.

PMID- 11521161
TI  - Comparative effects of the novel vasotocin analogue F-180 vs. vasopressin and
      terlipressin on systemic and splanchnic isolated vessels from portal hypertensive
      rats.
AB  - F-180 has been proposed as a new vasopressin analogue for the treatment of portal
      hypertension. This study investigates the contractile profile of F-180 compared
      to vasopressin and its analogue terlipressin on isolated systemic and splanchnic
      vessels from sham-operated and partial portal vein ligated (PPVL) rats. F-180
      (10(-9)-10(-6) M), vasopressin (10(-11)-10(-8) M) and terlipressin (10(-9)-10(-4)
      M) induced contraction of the mesenteric vein, aorta, iliac, tail and mesenteric
      arteries. The order of potency in these vessels was vasopressin (pD2
      approximately 9) > F-180 (pD2 approximately 8) > terlipressin (pD2 approximately
      6). Significant (P<0.01) differences between sham-operated and PPVL rats were
      noticed exclusively in the mesenteric vein, being the maximal effect of the three
      agonists at least twice greater in PPVL rats than in sham-operated rats. The
      order of sensitivity to the vasoconstrictors in vessels from PPVL rats was aorta
      < mesenteric artery << iliac artery approximately equal tail artery approximately
      equal mesenteric vein. The contractile profile of these peptides in each vessel
      from PPVL animals was quite similar, except in the mesenteric vein and the aorta.
      F-180 showed higher efficacy (P<0.01) than terlipressin in the mesenteric vein
      and lower (P<0.05) efficacy than vasopressin in the aorta. These findings suggest
      the existence of a vasoconstrictor territorial selectivity for vasopressin and
      its analogues, which could justify the efficacy of these drugs in portal
      hypertension therapy. In particular, F-180 appears to be a viable alternative to
      the classic vasopressin analogues.

PMID- 11521162
TI  - Release of non-neuronal acetylcholine from the human placenta: difference to
      neuronal acetylcholine.
AB  - The synthesis and release of non-neuronal acetylcholine, a widely expressed
      signaling molecule, were investigated in the human placenta. This tissue is free
      of cholinergic neurons, i.e. a contamination of neuronal acetylcholine can be
      excluded. The villus showed a choline acetyltransferase (ChAT) activity of 0.65
      nmol/mg protein per h and contained 500 nmol acetylcholine/g dry weight. In the
      absence of cholinesterase inhibitors the release of acetylcholine from isolated
      villus pieces amounted to 1.3 nmol/g wet weight per 10 min corresponding to a
      fractional release rate of 0.13% per min. The following substances did not
      significantly modify the release of acetylcholine: oxotremorine (1 microM),
      scopolamine (1 microM), (+)-tubocurarine (30 microM), forskolin (30 microM),
      ouabain (10 microM), 4alpha-phorbol 12,13-didecanoate (1 microM) and tetrodotoxin
      (1 microM). Removal of extracellular calcium, phorbol 12,13-dibutyrate (1 microM)
      and colchicine (100 microM) reduced the acetylcholine release between 30% and
      50%. High potassium chloride (54 mM and 108 mM) increased the acetylcholine
      release slightly (by about 30%). A concentration of 10 microM nicotine was
      ineffective, but 100 microM nicotine enhanced acetylcholine release gradually
      over a 50-min period without desensitization of the response. The facilitatory
      effect of nicotine was prevented by 30 microM (+)-tubocurarine. Inhibitors of
      cholinesterase (physostigmine, neostigmine; 3 microM) facilitated the efflux of
      acetylcholine about sixfold, and a combination of both (+)-tubocurarine (30
      microM) and scopolamine (1 microM) halved the enhancing effect. In conclusion,
      release mechanisms differ between non-neuronal and neuronal acetylcholine.
      Facilitatory nicotine receptors are present which are activated by applied
      nicotine or by blocking cholinesterase. Thus, cholinesterase inhibitors increase
      assayed acetylcholine by two mechanisms, protection of hydrolysis and stimulation
      of facilitatory nicotine receptors.

PMID- 11521163
TI  - Beneficial effect of HCL-31D in murine models of endotoxaemia.
AB  - We evaluated the effect of HCL-31D, a novel cAMP-specific phosphodiesterase
      inhibitor, on the induction of inducible nitric oxide synthase (iNOS) in
      lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma)-treated rat aortic
      smooth muscle cells (RASMC) and on survival in a murine model of severe
      endotoxaemia. Treatment of cultured RASMC with LPS and IFN-gamma resulted in an
      increase of nitrite, tumour necrosis factor (TNF-alpha) production and induction
      of iNOS mRNA. However, incubation with HCL-31D (1 approximately 50 microM) for 24
      h caused significant attenuation of nitrite and TNF-alpha formation as well as
      iNOS mRNA induction in a dose-dependent manner but no effect on iNOS activity in
      RASMC. In addition, administration of HCL-31D (5 mg/kg, i.p.) resulted in that
      the increase of both plasma nitrate and TNF-alpha levels induced by LPS in vivo
      was significantly reduced in LPS-treated rats. Treatment of conscious mice with a
      high dose of LPS (60 mg/kg, i.p.) to ICR mice resulted in a 24-h survival rate of
      only 10%. However, administration of HCL-31D (5 mg/kg, i.p. at 0 h and 6 h after
      LPS) improved the 24-h survival to 50%, indicating that HCL-31D has a beneficial
      effect in murine model endotoxaemia. These effects may be mainly due to
      inhibition of TNF-alpha formation and of the induction of iNOS. We proposed that
      the elevation of cAMP levels by HCL-31D may be involved in the prevention of TNF
      alpha formation and iNOS induction.

PMID- 11521164
TI  - Involvement of cyclic GMP and potassium channels in relaxation evoked by the
      nitric oxide donor, diethylamine NONOate, in the rat small isolated mesenteric
      artery.
AB  - The relative functional importance of potassium channels and cGMP-dependent
      pathways in the relaxation of vascular smooth muscle to the novel nitric oxide
      donor, diethylamine NONOate (DEA NONOate), was investigated in a resistance
      artery. The contribution from cGMP-dependent signalling pathways was examined by
      exposing arteries to 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), a
      selective inhibitor of soluble guanylyl cyclase, while the contribution through
      potassium channels was assessed with different sub-type-selective potassium
      channel blockers. DEA NONOate (3 nM-10 microM) evoked sustained relaxation in
      isolated segments of the rat small mesenteric artery contracted with
      phenylephrine (pEC50=6.7+/-0.2; n=11). The relaxation was attenuated
      significantly by either ODQ (10 microM; pEC50=5.8+/-0.4; n=7) or charybdotoxin
      (ChTX; 50 nM; pEC50=6.3+/-0.2; n=4), a peptide blocker of large conductance,
      calcium-activated potassium channels (BK(Ca)). The inhibitory effects of ODQ and
      ChTX were additive (pEC50=5.1+/-0.4; n=9). The selective inhibitor of BK(Ca)
      channels, iberiotoxin (IbTX; 30 nM), and 4-aminopyridine (4-AP; 1 mM), an
      inhibitor of voltage-gated potassium channels (Kv), failed to modify DEA NONOate
      evoked relaxation. However, in the combined presence of both ODQ and either IbTX
      or 4-AP the relaxation was attenuated significantly (n=3). The blocker of ATP
      modulated potassium channels (K(ATP)), glibenclamide (10 microM), and of small
      conductance calcium-activated potassium channels (SK(Ca)), apamin (30 nM), each
      failed to affect ODQ-sensitive or -resistant relaxations to DEA NONOate (n=3). In
      conclusion, relaxation to DEA NONOate in the rat isolated, small mesenteric
      artery can occur via both cGMP-dependent (ODQ-sensitive) and -independent (ODQ
      resistant) mechanisms. However, the contribution made to relaxation by potassium
      channels appears to be unmasked following pharmacological attenuation of cGMP
      dependent signalling pathways. The inhibitory action of ChTX suggests part of the
      cGMP-insensitive component involves the activation of potassium channels, a
      suggestion supported by the inhibitory actions of 4-AP and IbTX in the absence of
      cGMP.

PMID- 11521165
TI  - Contribution of both the sarcolemmal K(ATP) and mitochondrial K(ATP) channels to
      infarct size limitation by K(ATP) channel openers: differences from
      preconditioning in the role of sarcolemmal K(ATP) channels.
AB  - The roles of sarcolemmal ATP-sensitive K+ (sarcK(ATP)) and mitochondrial ATP
      sensitive K+ (mitoK(ATP)) channels in the cardioprotection induced by K(ATP)
      channel openers remain unclear, though the mitoK(ATP) channel has been proposed
      to be involved as a subcellular mediator in cardioprotection afforded by ischemic
      preconditioning (PC). In the present study, selective inhibitors of the
      sarcK(ATP) and mitoK(ATP) channels were used to examine the role of each channel
      subtype in infarct size limitation by KATP channel openers. Isolated rabbit
      hearts were perfused in the Langendorff mode with monitoring of the activation
      recovery interval (ARI) and subjected to 30-min global ischemia/2-h reperfusion
      to induce infarction. Before ischemia, hearts received 10 microM pinacidil, 100
      microM diazoxide, or PC with or without preceding infusion of a sarcK(ATP)
      channel-selective blocker (5 microM HMR1098) or a mitoK(ATP) channel-selective
      blocker (100 microM 5-hydroxydecanoate, 5-HD). ARI, an index of action potential
      duration, was shortened from 118+/-3 ms to 77+/-5 ms after 10 min of ischemia in
      untreated control hearts. Pinacidil shortened ARI before ischemia from 113+/-2 ms
      to 78+/-5 ms and enhanced the ARI shortening during ischemia. Diazoxide did not
      affect ARI before ischemia but accelerated ischemia-induced shortening of ARI.
      Infarct size as a percentage of the left ventricle (%IS/LV) was reduced by
      pinacidil and diazoxide from the control value of 47.2+/-4.0% to 4.5+/-1.5% and
      5.2+/-1.2%, respectively. HMR1098 significantly inhibited the shortening of ARI
      by ischemia, pinacidil and diazoxide and partially blocked infarct size
      limitation by these K(ATP) channel openers (%IS/LV=32.6+/-4.2% and 23.4+/-5.3%,
      respectively). Infusion of 5-HD did not modify the change in ARI caused by the
      K(ATP) channel openers but completely abolished cardioprotection (%IS/LV=46.0+/
      6.2% with pinacidil and 57.2+/-7.0% with diazoxide). PC with two episodes of 5
      min ischemia limited %IS/LV to 21.6+/-4.0%, and this protection was not inhibited
      by HMR1098. Neither HMR1098 nor 5-HD alone modified infarct size. In conclusion,
      both sarcK(ATP) and mitoK(ATP) channels may contribute to the anti-infarct
      tolerance afforded by pinacidil and diazoxide.

PMID- 11521166
TI  - Modulation of the cardiac autonomic transmission of pithed rats by presynaptic
      opioid OP4 and cannabinoid CB1 receptors.
AB  - We studied the effects of nociceptin, the endogenous ligand of the opioid OP4
      receptor, and of two cannabinoid receptor agonists WIN 55,212-2 and CP-55,940
      (0.001-1 micromol/kg each) on the neurogenic tachycardia and bradycardia in
      pithed rats. Electrical stimulation (1 Hz, 1 ms, 50 V for 10 s) of the
      preganglionic sympathetic nerve fibres and injection of nicotine 2 micromol/kg or
      isoprenaline 0.5 nmol/kg increased heart rate by about 70 beats/min (bpm) in
      pithed rats pretreated with atropine 1.5-2 micromol/kg. The electrically induced
      tachycardia was reduced dose dependently by nociceptin, WIN 55,212-2 and CP
      55,940 (by 60, 30 and 20% at the highest dose, respectively). The OP4 and
      cannabinoid receptor agonists diminished the nicotine- but not the isoprenaline
      stimulated increase in heart rate. In pithed rats pretreated with propranolol 3
      micromol/kg, vagal stimulation (5 Hz, 1 ms, 15 V for 10 s) or injection of
      methacholine (5-10 nmol/kg) decreased heart rate by about 30 bpm. Nociceptin, but
      not WIN 55,212-2 or CP-55,940 decreased the vagal bradycardia dose dependently
      (the inhibitory effect of 1 micromol/kg was about 40%). Nociceptin failed to
      modify the methacholine-induced decrease in heart rate. The OP4 receptor
      antagonists naloxone benzoylhydrazone 5 micromol/kg and/or [Phe1Psi(CH2-NH)Gly2]
      nociceptin(1-13)NH2 0.7 micromol/kg, but not the OP(1-3) receptor antagonist
      naloxone 10 micromol/kg, diminished the inhibitory action of nociceptin on the
      neurogenic tachycardia and bradycardia. The inhibitory effect of both cannabinoid
      receptor agonists on the neurogenic tachycardia was abolished by the CB1 receptor
      antagonist SR 141716 0.1 micromol/kg. The present data suggest that the
      postganglionic sympathetic nerve fibres innervating the rat heart are endowed
      with presynaptic opioid OP4 and cannabinoid CB1 receptors, activation of which
      inhibits the neurogenic tachycardia. The parasympathetic nerve fibres innervating
      the heart and causing bradycardia are endowed with presynaptic opioid OP4 but not
      cannabinoid receptors.

PMID- 11521167
TI  - The role of sensory neuropeptides in motor innervation of the hamster isolated
      urinary bladder.
AB  - In this study we have characterized the role of sensory fibers and of the sensory
      peptides, neurokinin A (NKA) and calcitonin gene-related peptide (CGRP), on the
      contractile responses evoked by single pulse electrical field stimulation (EFS)
      in the hamster urinary bladder. EFS of the hamster isolated urinary bladder
      produced twitch contractions which were unaffected by atropine but abolished by
      tetrodotoxin. The P2 purinoreceptor antagonist PPADS (30 microM) inhibited
      twitches by 66+/-4% on its own and by 78+/-3% in the presence of atropine. The
      selective tachykinin NK2 receptor antagonist nepadutant produced a slight but
      consistent reduction of twitch amplitude (-21+/-3%) at 1 microM. Addition of
      nepadutant to atropine and PPADS did not further increase their inhibitory
      effect. The application of hCGRP (10-300 nM) produced a concentration-dependent
      inhibition of twitches (Emax -38+/-3%, EC50=12 nM) and a small reduction of tone
      (0.5+/-0.09 mN). Similar effects were obtained with capsaicin (0.1-10 microM)
      which inhibited EFS-evoked contractions with an EC50 of 100.0 nM and a maximal
      effect of 34+/-4% inhibition at 1 microM. Under submaximal parameters of
      stimulation NKA (10 nM) increased the amplitude of twitches by 45+/-6% and
      produced a concentration-dependent tonic contraction (EC50=55.9 nM). The CGRP1
      receptor subtype antagonist, hCGRP(8-37), increased by 29+/-8% the EFS-evoked
      contractions and significantly reduced the response to 0.1 microM CGRP. Capsaicin
      (10 microM) increased both CGRP-LI and NKA-LI release from superfused slices of
      hamster urinary bladder by about sixfold and by about 70%, over baseline,
      respectively. A second application of capsaicin was ineffective, indicating a
      complete desensitization of sensory nerve efferent function. In the hamster
      urinary bladder the sensory neuropeptides NKA and CGRP are co-released by sensory
      fibers after stimulation either by EFS or capsaicin. However, the role of CGRP
      appears functionally predominant.

PMID- 11521168
TI  - Neurotoxicity of mercury sulfide in the vestibular ocular reflex system of guinea
      pigs.
AB  - A traditional Chinese mineral medicine, cinnabar, naturally occurring mercuric
      sulfide (HgS), is still occasionally prescribed, but the neurotoxic effects of
      HgS have not been elucidated. In this paper, an animal model of the purified HgS
      intoxication was established in guinea pigs in order to study neurotoxicity and
      pathophysiology of the vestibular ocular reflex system (VOR). Guinea pigs were
      dosed with HgS by gastric gavage (0.01, 0.1 and 1.0 g/kg per day) for 7
      consecutive days. By means of caloric testing coupled with the
      electronystagmographic (ENG) recording in guinea pigs, we have found that HgS at
      a dose of 0.1 g/kg induced reversible caloric hypofunction pattern and at a
      higher dose of 1.0 g/kg induced irreversible hypofunction of caloric test.
      Monitoring the mercury contents of various tissues (blood, kidney, liver and
      cerebellum) by continuous flow and cold vapor atomic absorption spectrometry
      (AAS) revealed that a certain amount of HgS could be absorbed from the
      gastrointestinal tract and was detectable in these tissues. In addition to the
      induced dysfunction of VOR system, HgS also caused disturbance of motor
      performance in guinea pigs. In enzyme assay, Na+/K+-ATPase activity of cerebellum
      was also significantly inhibited by HgS. Morphological studies showed partial
      cell loss only in the cerebellar Purkinje cell layer, but not in the granule cell
      layer, nor in the vestibular labyrinth. All of these findings suggest that
      cerebellar Purkinje cells are the sensitive target site responsible for HgS
      inducing dysfunctions of both VOR system and the motor performance in guinea
      pigs. Thus, it is concluded that caloric test coupled with ENG recording in VOR
      system is certainly a sensitive biomarker for monitoring the neurotoxicity of
      HgS.

PMID- 11521170
TI  - The effect of high-dose pentaerythritol tetranitrate on the development of
      nitrate tolerance in rabbits.
AB  - Experimental studies with therapeutic doses of pentaerythritol tetranitrate
      (PETN) have shown unexpected actions such as a lack of nitrate tolerance and
      vasoprotective effects in atherosclerosis. We investigated the effect of a 3-week
      treatment with low- (6 mg kg(-1) day(-1), n=10) and high-dose (100 mg kg(-1) day(
      1), n=10) oral PETN given twice daily on the development of nitrate tolerance in
      rabbits. We measured aortic relaxation in response to acetylcholine, S-nitroso-N
      acetyl-D,L-penicillamine and PETN, constriction in response to phenylephrine and
      production of reactive oxygen species (ROS). Mean aortic pressure (AOPmean) and
      heart rate were measured after a single oral dose of PETN (50 mg kg(-1), n=6) and
      after increasing doses of pentaerythritol dinitrate (PEDN, n=5) and
      pentaerythritol mononitrate (PEMN, n=5) in anaesthetized rabbits. Oral PETN, even
      at high dosage, was not associated with nitrate tolerance. None of the aortic
      ring studies showed a difference in the responses to the vasodilators, while the
      vasoconstriction to phenylephrine was slightly reduced in both PETN groups. The
      production of vascular ROS was also not different. Oral PETN reduced AOPmean
      transiently (-19.3+/-4.4%, P<0.01 vs. controls) and i.v. administration of both
      PEMN and PEDN reduced AOPmean dose dependently (P<0.05, ANOVA). These results
      suggest that oral PETN elicits minor nitrate tolerance. This unique feature might
      be due to the slow onset of vasodilator activity of the predominantly active
      metabolites PEDN and PEMN and might contribute to the vasoprotective activity of
      PETN in atherosclerosis.

PMID- 11521169
TI  - Inhibition of caffeine-induced Ca2+ release by adenosine in mammalian skinned
      slow- and fast-twitch fibres.
AB  - The present study performed on chemically skinned skeletal fibres was designed to
      compare the effects of adenosine on the Ca2+ sensitivity of contractile proteins
      and on caffeine-induced Ca2+ release in rat slow- (soleus) and fast-twitch (edl)
      muscles. The tension-pCa relationships were obtained by exposing triton X-100 (1%
      v/v) skinned fibres sequentially to solutions of decreasing pCa in the presence
      or in absence of adenosine. Then, changes in caffeine contracture due to
      adenosine were recorded on saponin (50 microg/ml) skinned fibres. The results
      show that the sensitivity to Ca2+ of contractile proteins in the presence of
      different concentrations of caffeine was not significantly modified by adenosine.
      However, it was proposed that adenosine (0.1-2 mM) reduced the Ca2+ released by
      caffeine (0.1-10 mM) from the sarcoplasmic reticulum in slow- and fast-twitch
      fibres and that the soleus was more sensitive to adenosine than edl muscle. The
      effects of specific A2a and A1 agonists and antagonists were also tested on
      caffeine contractures. It was found that the A1 antagonist reduced adenosine
      effect on caffeine response. Then it is proposed that adenosine modulates the
      sarcoplasmic reticulum Ca2+ release by a direct effect on the RyR1 receptors
      and/or by an indirect effect mediated by A1 receptors located at the sarcoplasmic
      level.

PMID- 11521171
TI  - Diadenosine tetraphosphate-gating of cardiac K(ATP) channels requires intact
      actin cytoskeleton.
AB  - Diadenosine polyphosphates (ApnA) have been recently discovered in the heart, and
      their levels found to be regulated by ischemia. These signaling molecules are
      believed to regulate cellular processes that alarm a cell to metabolic stress. In
      particular, changes in cardiac diadenosine polyphosphates (ApnA) levels may
      contribute to the regulation of ATP-sensitive K+ (K(ATP)) channel activity, an
      ion channel that couples the cellular metabolic state with membrane excitability.
      A feature of myocardial ischemia is the disruption of the actin cytoskeleton
      which critically regulates the behavior of K(ATP) channels. Whether the integrity
      of actin microfilaments regulates the interaction of ApnA with K(ATP) channels is
      not known. The inside-out configuration of the patch-clamp technique was applied
      to cardiomyocytes isolated from guinea-pig heart. Following patch excision, the
      prototype dinucleotide, diadenosine tetraphosphate (Ap4A), inhibited K(ATP)
      channel opening. Treatment of the internal side of membrane patches with either
      cytochalasin B or DNase I, disrupters of the actin cytoskeleton, prevented Ap4A
      induced inhibition of K(ATP) channel opening. Application of purified actin to
      DNase-treated membrane patches restored the ability of Ap4A to close K(ATP)
      channels. This study shows that inhibition of cardiac K(ATP) channel by Ap4A, a
      putative alarmone, requires intact subsarcolemmal actin network. Such interaction
      between K(ATP) channels, the cardiomyocyte cytoskeleton and intracellular Ap4A
      could affect different channel-dependent functions.

PMID- 11521172
TI  - Lipopolysaccharide-induced subsensitivity of protease-activated receptor-2 in the
      mouse salivary glands in vivo.
AB  - Protease-activated receptor-2 (PAR-2) acts as a modulator of multiple
      physiological/pathophysiological functions including salivary exocrine secretion.
      Given the supersensitivity of endothelial PAR-2 under endotoxaemia, we
      investigated if endotoxin/lipopolysaccharide (LPS) could alter the sensitivity of
      PAR-2 in the salivary glands. The in vivo salivation in response to i.v.
      administration of the PAR-2-activating peptide SLIGRL-NH2, but not of carbachol,
      gradually decreased 6-20 h after LPS administration in the mice. The LPS-induced
      hyporeactivity to the PAR-2 agonist was partially reversed by repeated
      administration of aprotinin, a non-specific protease inhibitor. PAR-2 mRNA levels
      in the salivary glands, as assessed by the semi-quantitative RT-PCR analysis,
      remained unchanged following LPS challenge. Our findings indicate that in
      contrast to the supersensitivity of endothelial PAR-2 as described previously,
      subsensitivity of PAR-2 in the salivary glands develops during the LPS-induced
      systemic inflammation, which might involve desensitisation of PAR-2 by endogenous
      proteases.

PMID- 11521173
TI  - NF449: a subnanomolar potency antagonist at recombinant rat P2X1 receptors.
AB  - Antagonistic effects of the novel suramin analogue 4,4',4",4"'-(carbonylbis(imino
      5,1,3-benzenetriylbis(carbonylimino)))tetrakis-benzene-1,3-disulfonic acid
      (NF449) were studied on contractions of the rat vas deferens elicited by
      alpha,beta-methylene ATP (alphabetameATP; mediated by P2X1 receptors),
      contractions of the guinea-pig ileal longitudinal smooth muscle elicited by
      alphabetameATP (mediated by P2X3 receptors) or adenosine 5'-O-(2-thiodiphosphate)
      (ADPbetaS; mediated by P2Y1 receptors), ATP-induced increases of [Ca2+]i in human
      embryonic kidney (HEK) 293 cells (mediated by P2Y2 receptors), inward currents
      evoked by ATP in follicle cell-free Xenopus laevis oocytes expressing rP2X1 or
      rP2X3 receptors and degradation of ATP by ecto-nucleotidases in folliculated
      Xenopus laevis oocytes. In addition, NF449 was examined for its P2 receptor
      specificity in rat vas deferens (alpha1A-adrenoceptors) and guinea-pig ileum
      (histamine H1 and muscarinic M3 receptors). At native (pIC50=7.15) and
      recombinant (pIC50=9.54) P2X1 receptors, NF449 was a highly potent antagonist.
      The P2X3 receptors present in guinea-pig ileum (pIC50=5.04) or expressed in
      oocytes (pIC50 approximately 5.6) were much less sensitive for NF449. It also was
      a very weak antagonist at P2Y1 receptors in guinea-pig ileum (pIC50=4.85) and
      P2Y2 receptors in HEK 293 cells (pIC50=3.86), and showed very low inhibitory
      potency on ecto-nucleotidases (pIC50<3.5). NF449 (100 microM) did not interact
      with alpha1A-adrenoceptors or histamine H1 and muscarinic M3 receptors. Thus, the
      antagonism by NF449 is highly specific for P2 receptors. In conclusion, the
      subnanomolar potency at rP2X1 receptors and the rank order of potency, P2X1 >>
      P2X3 > P2Y1 > P2Y2 > ecto-nucleotidases, make NF449 unique among the P2 receptor
      antagonists reported to date. NF449 may fill the long-standing need for a P2X1
      selective radioligand.

PMID- 11521174
TI  - New clues for the developing human biliary system at the porta hepatis.
AB  - The human biliary system is formed from the hepatic diverticulum, a structure
      which develops from the embryonic foregut in the fourth week of gestation. The
      cephalic portion of the hepatic diverticulum lies within the septum transversum,
      and gives rise to entodermal cells which become the primitive hepatocytes. The
      caudal part of the hepatic diverticulum is molded by mesenchyme to form the
      gallbladder, cystic duct, and extrahepatic bile duct. The gallbladder is
      initially tubular in shape, and undergoes morphological changes to become
      saccular during the 11th week of gestation. The extrahepatic bile duct elongates
      and widens as gestation progresses, and intramural mucus glands develop. There is
      no solid stage during the development of the extrahepatic bile duct. The
      extrahepatic bile duct is a well-defined tubular structure by the 6th week of
      gestation, whereas the intrahepatic biliary system during this period of
      gestation is represented by the primitive ductal plate. The ductal plate
      undergoes structural changes from the 11th week of gestation, beginning at the
      porta hepatis and progressing through gestation to the periphery of the liver.
      This remodeling process shapes the ductal plate from a flat sheath of biliary
      epithelium surrounding the portal vein branches into a network of interconnecting
      tubular structures. Mesenchyme plays an important role in ductal plate
      remodeling. The intrahepatic biliary system is in luminal continuity with the
      extrahepatic bile duct throughout gestation at the porta hepatis. The major bile
      ducts at the porta hepatis are fully formed by the 16th week of gestation.

PMID- 11521175
TI  - Pathology and pathogenesis of intrahepatic bile duct loss.
AB  - In recent years, the pathology and pathogenesis of bile duct loss have been
      extensively studied, and a number of hepatobiliary diseases have been added to
      the list of ductopenic diseases. In addition, the biology of biliary epithelial
      cells is now being studied with respect to bile duct loss, as well as biliary
      epithelial neoplasia. In this review, recent advances in pathogenetic and
      pathological studies of intrahepatic bile duct loss are described, with an
      emphasis on immune-mediated cholangiopathies. The bile duct loss, an acquired and
      pathologic process that occurs in the biliary tree, is recognizable as an absence
      of bile duct in an individual portad tract, and also as such absence in the
      vicinity of parallel running hepatic arterial branches that constitute the portal
      triad. Immunostaining with biliary cytokeratin and other carbohydrate materials
      is useful for the identification of biliary elements in the inflamed portal
      tracts or fibrous septa. The underlying processes responsible for bile duct loss
      include immunological, ischemic, infectious, metabolic, and toxic processes. Bile
      duct loss in primary biliary cirrhosis and primary sclerosing cholangitis is
      immune-mediated, that in interventional radiology using hepatic arterial branches
      is related to biliary ischemia, while that in hepatic allograft rejection is
      related to both immunological and ischemic insults. Bacterial and viral
      cholangitis with bile duct loss is an example of infectious cholangitis. The
      biliary tree maintains its homeostasis by renewal and dropout, and bile duct loss
      occurs mainly via biliary apoptosis. In some patients with bile duct loss, such
      as occurs in drug-induced injuries, the bile ducts regenerate and finally
      redistribute in the liver, while in other types of bile duct loss, the loss is
      progressive and is followed by vanishing bile duct syndrome, leading to biliary
      cirrhosis or liver transplantation. More analysis of the biology of biliary
      epithelial cells is mandatory for the evaluation of the pathobiology of bile duct
      loss, as well as for the effective restoration of biliary epithelial cells, in
      ductopenic liver diseases.

PMID- 11521176
TI  - Pathogenesis and treatment of bile duct loss after liver transplantation.
AB  - The bile duct is one of the main targets of immune reaction after liver
      transplantation. Bile duct loss, termed ductopenia or vanishing bile duct
      syndrome, is a typical pathological finding of chronic rejection (CR). The
      mechanism of bile duct loss in allograft rejection is twofold: T-cell mediated
      cytotoxicity and ischemic sequelae caused by obliterative arteriopathy. Whether
      or not CR is reversible remains controversial. Accumulating data show the
      reversibility of bile duct injury caused by immunoreaction, but not the
      reversibility of injuries caused by ischemia. In our living-related liver
      transplantation program at Kyoto University Hospital, the incidence of
      ductopenia, which indicates the incidence of CR, was 14 of 423 patients (3.3%),
      comparable to the result for cadaveric liver transplantation. The onset was
      within 1 year, except in 2 patients. Of the 14 patients with ductopenia, 2
      recovered without re-transplantation, and of the remaining 12 patients, 7
      underwent re-transplantation, and the other 5 died without a chance of re
      transplantation. The diagnosis of ductopenia was based on the pathological
      findings, which specify that more than 50% of the portal triad does not contain
      visible bile ducts. Recently, staging criteria of CR were proposed by an
      international panel, who recommended splitting CR into an early stage and a late
      stage. At present, no specific immunosuppressive regimen for CR has been
      developed; however, early diagnosis based on these new criteria, and the earlier
      implementation of enforced immunosuppression, with conventional drugs, may be
      beneficial for a further reduction in CR.

PMID- 11521177
TI  - Current status of surgery and transplantation in the management of hepatocellular
      carcinoma: an overview.
AB  - Despite many therapeutic advances in the field of hepatocellular carcinoma over
      the past two decades, this disease continues to be a major cause of cancer
      related mortality worldwide. This review focuses on the recent advances in
      surgical technique, perioperative management, and transplantation of cirrhotic
      and noncirrhotic patients with hepatocellular carcinoma. Liver resection
      continues to be the mainstay of curative treatment in noncirrhotic patients and
      selected cirrhotic patients with small tumors and preserved liver function.
      Transplantation should be advocated for patients with poor liver function and
      localized lesions or for patients with large fibrolamellar carcinomas that are
      otherwise unresectable. Surgery has a definite role in the management of hepatic
      recurrences in the absence of systemic dissemination. Newer advances in the
      therapeutic armamentarium, such as cryotherapy, radiofrequency ablation,
      microwave coagulation, and ethanol injections are discussed, and their overall
      efficacy assessed.

PMID- 11521178
TI  - Technical innovation for noninvasive and early diagnosis of biliary atresia: the
      ultrasonographic "triangular cord" sign.
AB  - In this article, we introduce our experience regarding a new and noninvasive
      diagnostic tool, using ultrasonography, for the early and definite diagnosis of
      biliary atresia. We have focussed on the ultrasonographic image of the cone
      shaped periportal fibrous mass in infants with biliary atresia since 1992, and
      have finally identified a triangular or band-like periportal echogenicity
      ("triangular cord" sign), mainly cranial to the portal vein. Based on our
      experience and other reports from Japan and Singapore, the ultrasonographic
      triangular cord sign is a simple, time-saving, highly reliable, and definite tool
      in the diagnosis of biliary atresia from infantile intrahepatic cholestasis,
      representing a positive predictive value greater than 95%. We have proposed a new
      diagnostic strategy in the evaluation of infantile cholestasis, with emphasis on
      the ultrasonographic triangular cord sign.

PMID- 11521179
TI  - A new reconstructive procedure after segmental pancreatectomy: an experimental
      study of pancreatic end-to-end (duct-to-duct) anastomosis.
AB  - We produced experimental models of pancreatic end-to-end anastomosis, including
      ductal end-to-end anastomosis (with or without stent) and pancreaticojejunostomy,
      using mongrel dogs, with a view to evaluating reconstructive procedures after
      segmental pancreatectomy. We examined macroscopic findings, pancreatograms, and
      microangiographic and histopathological findings to determine whether pancreatic
      end-to-end anastomosis was as practicable as pancreaticojejunostomy. Macroscopic
      findings showed no suture failure in any animal in the end-to-end anastomosis
      group. Pancreatography revealed obstruction of the stent tube in the stent
      subgroup, but good patency in the no-stent subgroup. On the imaging of the
      microvasculature in the end-to-end anastomosis group, proliferation of
      neovascular vessels and formation of communicating vessels were detected.
      Histopathologically, no suture failure was detected, and the viability of the
      pancreatic end-to-end anastomosis was confirmed. From this experiment, we
      concluded it that it was possible to employ pancreatic end-to-end anastomosis
      after segmental pancreatectomy in the clinical situation.

PMID- 11521180
TI  - Comparison of ultrasonically activated scalpel versus conventional division for
      the pancreas in distal pancreatectomy.
AB  - PURPOSE: The goal of this study was to compare the benefits and complications of
      using an ultrasonically activated scalpel and conventional division of the
      pancreas in patients undergoing a distal pancreatectomy. METHODS: A retrospective
      review was performed of all patients who underwent distal pancreatectomy at the
      Department of Surgery, Koshigaya Municipal Hospital. In the ultrasonically
      activated scalpel (US) group (n = 11), the pancreas was divided using coagulation
      shears. The stump of the pancreas was left open without parenchymal suturing. In
      the conventional surgical division (CV) group (n = 20), the pancreas was cut with
      a knife and the stump was oversewn with interrupted mattress sutures. The main
      pancreatic duct was ligated in all patients in both groups. The postoperative
      courses in the two groups were then compared in terms of postoperative serum
      amylase levels and the incidence of pancreatic fistulas. RESULTS: The
      postoperative serum amylase levels were significantly lower in the US group than
      in the CV group (P < 0.01 on the day of operation). The incidence of pancreatic
      fistulas was also significantly lower in the US group (0%) than in the CV group
      (30%) (P = 0.04). CONCLUSIONS: The use of the ultrasonically activated scalpel
      was found to reduce the incidence of pancreatic fistula in distal pancreatectomy.
      Furthermore, the use of this device without any clamping or parenchymal suturing
      may reduce the damage to the remnant pancreas.

PMID- 11521181
TI  - Surgical treatment of recurrent hepatocellular carcinoma based on the mode of
      recurrence: repeat hepatic resection or ablation are good choices for patients
      with recurrent multicentric cancer.
AB  - Hepatocellular carcinomas (HCC) often recur after curvative resection. Recurrence
      in the remnant liver originates from intrahepatic metastasis (IM) from the
      primary resected tumor, and/or from multicentric (MC) occurrence. In order to
      achieve better survival after intrahepatic recurrence in HCC patients, we have
      surgically treated patients according to the recurrence pattern. In this study,
      we investigated the advantage of repeat surgery for MC recurrent HCC. The
      subjects were 176 patients who had undergone primary macroscopically complete
      tumor removal for HCC at our department from 1984 to 1999. Differential diagnosis
      of IM and MC recurrence was done by pathological analysis. Twenty-nine of the 149
      patients with recurrence (19.5%) underwent a total of 31 second and third
      operations. Of the 29 patients, 18 had MC (14 received repeat hepatectomy and 4,
      microwave tissue coagulation [MTC]), 7 had IM (4 had repeat hepatectomy and 3,
      MTC), and, in 4 patients, pathological investigation failed to determine the mode
      of recurrence. The 1-, 3-, and 5-year survival rates for MC patients after the
      repeat operations were 100%, 69.7%, and 58.1%, respectively, and the 1-, 3-, and
      5-year survival rates for the IM patients were 57.1%, 14.3%, and 14.3%,
      respectively. Survival after the repeat operation was significantly better in the
      MC group than in the IM group (P = 0.0016). Moreover, there was no significant
      difference between survival in the MC group after a repeat operation and survival
      in control patients after an initial hepatectomy (P = 0.9282). These results
      indicated that patients with resectable or ablative recurrent MC HCC have almost
      the same survival benefit after repeat operations as patients who undergo initial
      curative resection of HCC.

PMID- 11521182
TI  - Expansion of an ablated site and induction of apoptosis after microwave
      coagulation therapy in rat liver.
AB  - BACKGROUND/PURPOSE: Microwave coagulation therapy (MCT), one of the ablation
      therapies, has been widely used to treat liver cancers, yielding excellent
      clinical results. Despite its efficacy, the precise events that take place in the
      ablated liver after MCT remain unknown. We investigated sequential histologic
      changes around MCT sites and the relationship between MCT and apoptosis in rat
      liver. METHODS: One session of MCT at 30 W was applied to rat liver. The rats
      were killed at 0, 2, 6, 12, 24, 72, and 168 h after MCT. The liver surface area
      was measured for sequential evaluations of the size of the impaired field (i.e.,
      the liver surface affected by MCT). The size of the impaired field was assessed
      by measuring the area that showed macroscopic changes in color with a relatively
      clear border. To assess apoptosis, we examined terminal deoxynucleotidyl
      transferase d-uridine triphosphate nick end labeling stained sections, determined
      the positive cell count for DNA fragmentation, and observed DNA ladder formation
      by gel electrophoresis. Caspase-3 activity at the ablated margin was measured for
      the enzymatic evaluation of apoptosis. RESULTS: The impaired field gradually
      expanded through 12 h after MCT. Caspase-3 activity increased four fold from the
      baseline, peaking at 2 h after MCT, and DNA fragmentation, confirmed by DNA
      ladder formation, was significantly increased at 6 h. CONCLUSIONS: Alterations in
      the ablated liver tissue indicated that the activation of caspase-3 around the
      MCT site was followed by apoptosis and expansion of the impaired field. The
      expansion continued until 12 h after MCT, and this may be beneficial for the
      local control of liver cancer.

PMID- 11521183
TI  - Surgical bypass versus metallic stent for unresectable pancreatic cancer.
AB  - With the development of interventional radiology and endoscopy, the practice of
      inserting expandable metallic stents for malignant jaundice has become
      widespread. Many studies have compared surgical bypass with polyethylene stents,
      or metallic stents with polyethylene stents. However, few data are available on
      the comparison of surgical bypass and metallic stents. The aim of this study was
      to compare the patient's postprocedure course and the cost performance of
      surgical bypass and metallic stents in patients with unresectable pancreatic
      cancer. The parameters analyzed were the rates of procedural and therapeutic
      success, duration of hospital stay, prevalence of early and late complications,
      cost performance, and prognosis. The rates of procedural and therapeutic success
      were excellent with both palliative treatments. With surgical bypass, there was a
      low prevalence of late complications, but duodenal obstruction sometimes occurred
      in patients without gastric bypass. With metallic stents, there was shorter
      hospitalization and lower cost, but a higher prevalence of late complications.
      Stent occlusion tended to occur in patients with uncovered metallic stents. There
      was no difference in the prognosis between the two palliative treatments. Thus,
      in consideration of the poor prognosis of pancreatic cancer, in patients with
      unresectable pancreatic cancer, insertion of covered metallic stents would be
      preferable to surgical bypass, because of the subsequent short hospitalization
      and the low cost. On the other hand, in patients with a relatively long expected
      prognosis, or in those with existing duodenal obstruction, biliary bypass with
      gastrojejunostomy may provide an advantage.

PMID- 11521184
TI  - Double cancers in the common bile duct: molecular genetic findings with an
      analysis of LOH.
AB  - We report a 69-year-old man with double cancers in the common bile duct. One
      cancer was located between the superior and middle parts of the bile duct, while
      the other cancer was in the inferior part of the bile duct. Pylorus-preserving
      pancreatoduodenectomy was performed. There was no communication between the two
      cancers in either the mucosal layer or the subepithelial layer. On pathological
      examination, the upper cancer was diagnosed as poorly differentiated
      adenocarcinoma, while the lower one was found to be moderately differentiated
      adenocarcinoma. We analyzed loss of heterozygosity (LOH), using microsatellite
      markers on five chromosomal arms, in both the upper and the lower cancers. Both
      cancers showed common regions of LOH at 5q, 6q, 9p, 17p, and 18q, whereas the
      upper cancer showed one additional region of LOH at 8p, thus suggesting
      progression, due to the acquisition of the additional LOH, in the upper cancer.
      No LOH was observed in the region between the two cancers. The presence of one
      additional LOH in the upper cancer suggests that the upper cancer was a
      metastasis of the lower one.

PMID- 11521185
TI  - Left-hand-assisted laparoscopic resection of hepatocellular carcinoma in an
      accessory liver.
AB  - We report a left-hand-assisted laparoscopic resection of hepatocellular carcinoma
      that developed in an accessory liver in a 47-year-old man. Preoperative
      assessment of the location of the tumor and the feeder vessels by combined
      selective angiography and computed tomography studies predicted the feasibility
      of laparoscopic procedures for complete removal of the tumor. In an attempt to
      avoid direct contact of the tumor capsule with rigid instruments during the
      operation, left-hand-assisted procedures were attempted. The encapsulated mass, 6
      x 5 x 3 cm in size, was located on the posterior side of the left diaphragm, and
      a thin stalk between the tumor and the margin of the left lateral segment of the
      liver proper was recognized. Hand-assisted procedures ensured the complete
      mobilization of the lesion with an adequate margin, without any unexpected
      capsular tear. Left-hand-assisted laparoscopic procedures would be feasible for
      the easy and safe resection of localized hepatocellular carcinoma developing in
      an accessory liver.

PMID- 11521186
TI  - Eight multicentric hepatocellular carcinomas occurring in the same segment of the
      liver.
AB  - We present a rare case of eight multicentric hepatocellular carcinomas (HCCs)
      occurring in the same segment of the liver. In a 66-year-old Japanese man,
      multiple liver tumors were detected during follow-up of chronic hepatitis C
      infection, and he was admitted to our hospital in 1995. Ultrasonography (US)
      showed eight tumors, each measuring between 10 and 15 mm in diameter, in the
      right lobe, and a 10-mm tumor in the left lobe. Angio-ultrasonography (US) showed
      no enhancement of the tumors, and multicentric occurrence was suspected. Portal
      angio-US showed eight tumors in the right lobe located in the anterior segment.
      Accordingly, anterior segmentectomy and partial resection of the S3 subsegment
      were performed, in December, 1995. On histological examination, all eight tumors
      in the anterior segment and the tumor in the S3 subsegment were well
      differentiated HCC. The liver parenchyma showed cirrhosis. The grade and stage of
      hepatitis did not differ between the anterior segment and the S3 subsegment, but
      irregular regeneration of hepatocytes was more prominent in the anterior segment.
      The multicentric occurrence of HCCs in the anterior segment may be related to the
      more severe damage caused by chronic hepatitis in the anterior segment than in
      the left lobe of the liver.

PMID- 11521187
TI  - Nonfunctioning islet cell carcinoma of the pancreas associated with massive intra
      abdominal hemorrhage.
AB  - Pancreatic islet cell tumors are rarely associated with intra-abdominal
      hemorrhage. We report herein a rare case of nonfunctioning islet cell carcinoma
      associated with massive hemorrhage into the abdominal cavity caused by
      spontaneous rupture of the tumor. A 44-year-old man presenting with sudden upper
      abdominal pain was admitted to his local hospital on April 18, 1994. On April 19,
      a laparotomy was performed with the diagnosis of peritonitis. Massive hemorrhage
      of unknown origin occurred, and he was transferred to our hospital in a state of
      hypovolemic shock. Imaging findings revealed massive hematoma in the abdominal
      cavity and a hypervascular tumor arising from the body of the pancreas. Because
      the hemorrhage was life-threatening, an emergent re-laparotomy was performed on
      April 20. Apart from the massive hemorrhage, a pancreatic tumor (60 x 35 x 30 mm
      in size) with spontaneous rupture was noted. Distal pancreatectomy, combined with
      splenectomy and removal of the hematoma, was performed. Histological findings
      revealed an islet cell carcinoma of the pancreas with venous invasion. Peritoneal
      dissemination, liver metastasis, and lymph node metastasis were not observed. The
      patient is alive without recurrence 6 years and 5 months after the operation.

PMID- 11521188
TI  - Identification of p21 as a target of cycloheximide-mediated facilitation of CD95
      mediated apoptosis in human malignant glioma cells.
AB  - Human glioma cell lines differ in their requirement for the inhibition of protein
      synthesis to activate the CD95-dependent killing pathway. CD95 ligand (CD95L)
      induced mitochondrial cytochrome c release and processing of caspases 3, 7, 8 and
      9 in LN-18 cells in the absence of an inhibitor of protein synthesis,
      cycloheximide (CHX). These biochemical changes were observed in LN-229 cells only
      in the presence of CHX. The viral caspase inhibitor, cytokine response modifier
      (crm)-A, inhibited mitochondrial cytochrome c release, caspase processing and
      cell death under all conditions. Ectopic expression of BCL-X(L) prevented
      processing of caspase 8 in LN-18 cells but not in LN-229 cells. Thus, caspase 8
      activation is amplified through the release of cytochrome c in LN-18 cells but
      occurs mainly at the receptor in LN-229 cells. In contrast to BCL-2, BCL-X(L), X
      linked inhibitor-of-apoptosis protein (XIAP) and FLICE-inhibitory protein (FLIP),
      the levels of the cyclin-dependent kinase (CDK) inhibitor, p21Waf/Cip1, rapidly
      decreased in response to CHX. P21 antisense oligonucleotides promoted caspase
      activation and mitochondrial cytochrome c release and induced strong
      sensitization to CD95-mediated apoptosis. These data place potentiating effects
      of CHX (i) to the activation of caspase 8 at the receptor in LN-229 cells as well
      as (ii) to a down-stream target at least in LN-18 cells, but probably both cell
      lines, that may be identical with p21Waf/Cip1.

PMID- 11521189
TI  - Inhibitors of histone deacetylase arrest cell cycle and induce apoptosis in
      cervical carcinoma cells circumventing human papillomavirus oncogene expression.
AB  - Histone deacetylase (HDAC) inhibitors sodium butyrate and trichostatin A arrest
      human papillomavirus (HPV)-positive carcinoma cells in G1 to S transition of the
      cell cycle, which is paralleled by an up-regulation of the cyclin-dependent
      kinase inhibitors (CKIs) p21CIP1 and p27KIP1 as well as the complete loss of cdk2
      activity. Although HPV expression was hitherto thought to be required to maintain
      a proliferative phenotype of these cells, cdk2 suppression is achieved even in
      the presence of ongoing viral transcription. While CKIs normally cannot exert
      their cdk2-inhibitory function in the presence of the viral oncoprotein E7, co
      immunoprecipitation experiments revealed that E7 binding is prevented. Increase
      of p27KIP1 correlates with down-regulation of p45SKP2, a component of the
      ubiquitin-protein ligase SCF(SKP2) controlling the half-life of regulatory
      proteins during the cell cycle. HDAC inhibition also triggered an E7-dependent
      degradation of pRb, while the levels of E2F remained unaffected. The presence of
      free intracellular E2F and the concomitant up-regulation of CKIs during G1 arrest
      results in a 'conflicting growth situation', which finally renders the cells to
      undergo apoptosis. These data provide novel molecular insights into how the
      transforming potential of HPV can be bypassed and open new therapeutical
      perspectives for the treatment of cervical cancer.

PMID- 11521190
TI  - NF-kappaB/RelA transactivation is required for atypical protein kinase C iota
      mediated cell survival.
AB  - In chronic myelogenous leukemia (CML), the oncogene bcr-abl encodes a
      dysregulated tyrosine kinase that inhibits apoptosis. We showed previously that
      human erythroleukemia K562 cells are resistant to antineoplastic drug (taxol)
      induced apoptosis through the atypical protein kinase C iota isozyme (PKC iota),
      a kinase downstream of Bcr-Abl. The mechanism(s) by which PKC iota mediates cell
      survival to taxol is unknown. Here we demonstrate that PKC iota requires the
      transcription factor nuclear factor-kappaB (NF-kappaB) to confer cell survival.
      At apoptosis-inducing concentrations, taxol weakly induces IkappaB(alpha)
      proteolysis and NF-kappaB translocation in K562 cells, but potently induces its
      transcriptional activity. Inhibition of NF-kappaB activity (by blocking
      IkappaB(alpha) degradation) significantly sensitizes cells to taxol-induced
      apoptosis. Likewise, K562 cells expressing antisense PKC iota mRNA or kinase dead
      PKC iota (PKC iota-KD) are sensitized to taxol; these cells are rescued from
      apoptosis by NF-kappaB overexpression. Expression of constitutively active PKC
      iota (PKC iota-CA) upregulates NF-kappaB transactivation and rescues cells from
      apoptosis in the absence of Bcr-Abl tyrosine kinase activity. Using a chimeric
      GAL4-RelA transactivator, we find that taxol potently activates GAL4-RelA
      dependent transcription. This activation was further upregulated by expression of
      PKC iota-CA and inhibited by expression of PKC iota-KD. Our results indicate that
      RelA transactivation is an important downstream target of the PKC iota-mediated
      Bcr-Abl signaling pathway and is required for resistance to taxol-induced
      apoptosis.

PMID- 11521191
TI  - E1A modulates phosphorylation of p130 and p107 by differentially regulating the
      activity of G1/S cyclin/CDK complexes.
AB  - We have previously shown that the adenoviral 12S E1A protein modulates the
      phosphorylation status of p130 and p107 without apparent changes in the cell
      cycle dependent phosphorylation of the retinoblastoma protein. Here we report on
      the mechanisms by which E1A modifies differentially the phosphorylation status of
      pocket proteins. In human U-2 OS osteosarcoma cells transiently expressing E1A,
      ectopic expression of D-type cyclins alone or combined, but not cyclins E and/or
      A, fully rescues E1A-mediated block in hyperphosphorylation of p130 to form 3.
      However, cyclins E and A, individually or together, induce hyperphosphorylation
      of p130 to species with intermediate mobility. Phosphopeptide maps indicate that
      E1A inhibits phosphorylation of sites phosphorylatable by CDKs. One of these
      sites is Ser-1044. The effects of blocking the activities of endogenous and
      exogenous cyclins with p16 and dominant negative CDK2 in E1A expressing cells
      further indicate that p130 is phosphorylated by both D-type cyclin and cyclin
      E/CDK complexes and that E1A modulates the activity of these G1/S CDKs by
      independent mechanisms. Stable expression of E1A in MC3T3-E1 cells leads to
      downregulation of D-type cyclins, and upregulation of cyclins E and A. This is
      accompanied by increased CDK2 kinase activity. Downregulation of D-type cyclins
      in these cells correlates with a block on both p130 hyperphosphorylation to form
      3 and hyperphosphorylation of p107. This is rescued by D-type cyclins but not by
      cyclin E. In addition, we show that the upregulation of cyclins E and A is at
      least partially dependent on an intact pocket protein/E2F pathway, but
      downregulation of D-type cyclins is not. Moreover, we provide evidence that while
      the lack of a functional pRB pathway also results in a block on
      hyperphosphorylation of p130 to form 3, this is not sufficient to induce
      constitutive expression of p130 form 2b.

PMID- 11521192
TI  - Independent control of cell survival by Raf-1 and Bcl-2 at the mitochondria.
AB  - Bcl-2 family proteins play a critical role in the regulation of cell survival by
      controlling the activation of the cell death executing caspase machinery. Recent
      work demonstrated that they also provide a link between growth factor signaling
      and cell survival control. Raf-1 has been identified initially as an essential
      component of the mitogenic Ras-Raf-MEK-ERK cascade. However, expression of
      oncogenic Raf-1 also efficiently suppresses apoptotic cell death. This process
      requires mitochondrial translocation of Raf-1 which can be achieved either by co
      expression of the anti-apoptotic protein Bcl-2 or by fusion with the
      transmembrane domain of the yeast outer mitochondrial membrane protein Mas 70p.
      It is currently unclear how mitochondrial Raf-1 prevents apoptosis. One possible
      mechanism involves the phosphorylation of the pro-apoptotic protein Bad resulting
      in the restoration of Bcl-2 function. Alternatively, the role of Bcl-2 could be
      limited to the mitochondrial translocation of Raf-1 and survival signaling by Raf
      1 is Bcl-2 independent. To test for the mutual requirement of Raf-1 and Bcl-2 in
      apoptosis suppression the individual proteins were singly tested for survival
      activity in a genetic background which precludes the expression of the other. The
      results obtained in these studies demonstrate that ablation of Raf-1 or Bcl-2
      expression in fibroblast cells significantly increases the sensitivity towards
      doxorubicin induced cell death. Reversion of the mutant phenotype could be
      achieved in either case by introducing a functional bcl-2 gene or a mitochondria
      targeted version of oncogenic Raf-1, demonstrating that each protein by itself is
      sufficient to confer protection. Our data thus suggest the existence of two
      separate pathways of survival signaling at the mitochondria controlled either by
      Bcl-2 or by Raf-1.

PMID- 11521193
TI  - Bax translocation is crucial for the sensitivity of leukaemic cells to etoposide
      induced apoptosis.
AB  - Bax translocation from cytosol to mitochondria is believed to be a crucial step
      for triggering cytochrome c release from mitochondria. However, it is unclear
      whether Bax translocation is associated with Bax induction by DNA damaging
      agents. The induction of Bax in response to DNA damaging agents has been
      considered to be linked with p53. In this study, we used the p53 negative human
      chronic myeloid leukaemia K562 cell line. Bax up-regulation occurred at the whole
      cell level after DNA damage induced by etoposide. However, after incubation with
      etoposide, Bax failed to translocate to mitochondria and as a result, the
      apoptotic process was blocked. A Bax stable transfectant, the K/Bax cell line,
      expressed more Bax protein in the cytosol, mitochondria and nuclei. This Bax
      overexpression induced cytochrome c release, a reduction of cytochrome c oxidase
      activity and mitochondrial membrane potential (Delta(Psi)m). However, Bax-induced
      apoptosis was blocked downstream of mitochondria in K562 cells. The increased
      levels of mitochondrial Bax sensitized cells to etoposide-induced activation of
      caspases-2, -3 and -9 and apoptosis. However, after transient transfection with
      the Apaf-1 gene, K/Bax cells were sensitized to etoposide-induced caspase
      activation and apoptosis to a larger extent compared with Bax or Apaf-1
      transfection alone. We therefore conclude that two mechanisms contribute to the
      resistance of K562 cells to etoposide-induced apoptosis; firstly failure of Bax
      targeting to mitochondria and, secondly, deficiency of Apaf-1. Uncoupling of Bax
      translocation from Bax induction can occur in response to etoposide-induced DNA
      damage.

PMID- 11521194
TI  - Disruption of BRCA1 LXCXE motif alters BRCA1 functional activity and regulation
      of RB family but not RB protein binding.
AB  - The tumor suppressor activity of the BRCA1 gene product is due, in part, to
      functional interactions with other tumor suppressors, including p53 and the
      retinoblastoma (RB) protein. RB binding sites on BRCA1 were identified in the C
      terminal BRCT domain (Yarden and Brody, 1999) and in the N-terminus (aa 304-394)
      (Aprelikova et al., 1999). The N-terminal site contains a consensus RB binding
      motif, LXCXE (aa 358-362), but the role of this motif in RB binding and BRCA1
      functional activity is unclear. In both in vitro and in vivo assays, we found
      that the BRCA1:RB interaction does not require the BRCA1 LXCXE motif, nor does it
      require an intact A/B binding pocket of RB. In addition, nuclear co-localization
      of the endogenous BRCA1 and RB proteins was observed. Over-expression of wild
      type BRCA1 (wtBRCA1) did not cause cell cycle arrest but did cause down
      regulation of expression of RB, p107, p130, and other proteins (e.g., p300),
      associated with increased sensitivity to DNA-damaging agents. In contrast,
      expression of a full-length BRCA1 with an LXCXE inactivating mutation (LXCXE-
      >RXRXH) failed to down-regulate RB, blocked the down-regulation of RB by wtBRCA1,
      induced chemoresistance, and abrogated the ability of BRCA1 to mediate tumor
      growth suppression of DU-145 prostate cancer cells. wtBRCA1-induced
      chemosensitivity was partially reversed by expression of either Rb or p300 and
      fully reversed by co-expression of Rb plus p300. Our findings suggest that: (1)
      disruption of the LXCXE motif within the N-terminal RB binding region alters the
      biologic function of BRCA1; and (2) over-expression of BRCA1 inhibits the
      expression of RB and RB family (p107 and p130) proteins.

PMID- 11521195
TI  - The role of the insulin receptor substrate-1 in the differentiation of rat
      hippocampal neuronal cells.
AB  - H19-7/IGF-IR cells are rat hippocampal cells expressing a human IGF-I receptor,
      which differentiate to a neuronal phenotype when stimulated by IGF-I at 39
      degrees C. H19-7/IGF-IR cells have low levels of expression of insulin receptor
      substrate-l (IRS-1), a major substrate of the IGF-IR. IGF-I induces serine
      phosphorylation and down-regulation of the endogenous IRS-1 upon differentiation
      of H19-7/IGF-IR cells. The profound influence of IRS-1 on differentiation of H19
      7/IGF-IR cells was confirmed by transfecting these cells with a plasmid
      expressing mouse IRS-1. Over-expression of wild type IRS-1 in H19-7/IGF-IR cells
      abolishes IGF-I-induced differentiation at 39 degrees C. A mutant of IRS-1
      lacking the PTB domain loses the ability to inhibit the differentiation program.
      H19-7/IGF-IR/IRS-1 cells at 39 degrees C show a stronger and prolonged activation
      of Akt, when compared to H19-7/IGF-IR cells. The role of Akt in the inhibition of
      the differentiation program was confirmed by using the inhibitor of Class I PI3
      kinases LY29400, which restores IGF-I-induced differentiation of H19-7/IGF-IR/IRS
      1 cells. H19-7/IGF-IR/IRS-1 cells show a strong reduction in MAP kinases
      signaling, which is related to the superactivation of Akt. This was confirmed by
      expressing in H19-7/IGF-IR cells a constitutively active Akt, which inhibited MAP
      kinases activation in these cells. These experiments confirm the importance of
      MAPK in the mechanism of IGF-I-mediated differentiation of H19-7/IGF-IR cells

PMID- 11521196
TI  - Expression, cellular distribution and protein binding of the glioma amplified
      sequence (GAS41), a highly conserved putative transcription factor.
AB  - The glioma amplified sequence 41 (GAS41) was previously isolated by
      microdissection mediated cDNA capture from the glioblastoma multiforme cell line
      TX3868 and shown to be frequently amplified in human gliomas. We determined the
      complete cDNA sequence of the GAS41 gene, demonstrated that the GAS41 protein is
      evolutionarily conserved, specifically at the N-terminus, and identified the
      yeast transcription factor tf2f domain within the GAS41 sequence. A human
      multiple-tissue Northern blot revealed ubiquitous expression of GAS41 with the
      highest expression in human brain. After generating polyclonal antibodies we
      found GAS41 protein expression in the nucleus of the TX3868 cell line by Western
      blot analysis and immunofluorescence microscopy. The nuclear localization was
      confirmed for several human tumors including gliomas of different grades of
      malignancy. In neuroblastoma however, GAS41 was found in the nucleoli but not in
      the nucleoplasm. Yeast two-hybrid screening of the TX3868 cell line identified
      the nuclear mitotic apparatus protein (NuMA), the KIAA1009 protein, and prefoldin
      subunit 1 (PFDN1) as potential interacting partners of GAS41. We generated a
      polyclonal antibody against the KIAA1009 protein and we demonstrated that the
      KIAA1009 protein is a nuclear protein, which appears to be co-localized with the
      GAS41 protein and NuMA.

PMID- 11521197
TI  - Involvement of Wnt signaling pathway in murine medulloblastoma induced by human
      neurotropic JC virus.
AB  - By using the early genome of the human neurotropic polyomavirus, JCV, we have
      created transgenic animals that develop cerebellar primitive neuroectodermal
      tumors which model human medulloblastoma. Expression of T-antigen was found in
      some, but not all, tumor cells, and examination of the clonal cell lines derived
      from the tumor population showed enhanced tumorigenicity of cells expressing T
      antigen in comparison to T-antigen negative cells. Considering the earlier notion
      on the potential involvement of beta-catenin with human medulloblastoma, we
      investigated various components of the Wnt signaling pathway including beta
      catenin, its partner transcription factor, LEF-1, and their downstream target
      gene c-myc in these two cell populations. Immunohistochemical staining of the
      cells revealed enhanced nuclear appearance of beta-catenin in T-antigen positive
      cells. Results from Western blot showed higher levels of beta-catenin and LEF-1
      in T-antigen positive cells in comparison to those in T-antigen negative cells.
      The enhanced level of LEF-1 expression correlated with the increase in DNA
      binding activity of this protein in nuclear extracts of T-antigen positive cells.
      Results from Northern and Western blot analyses revealed that the level of c-myc
      expression is augmented both at the RNA and protein levels in T-antigen positive
      cells. These observations corroborated results from transfection studies
      indicating the ability of JCV T-antigen to stimulate c-myc promoter activity.
      Further, co-transfection experiments revealed that the amount of c-myc and T
      antigen protein in tumor cells may dictate the activity of JCV early promoter in
      these cells. These observations are interesting in light of recent discoveries on
      the association of JCV with human medulloblastoma and suggest that communication
      between JCV and the Wnt pathway may be an important event in the genesis of these
      tumors.

PMID- 11521198
TI  - Early-onset colorectal cancer with stable microsatellite DNA and near-diploid
      chromosomes.
AB  - Colorectal cancer has been described in terms of genetic instability selectively
      affecting either microsatellite sequences (MIN) or chromosome number and
      structure (CIN). A subgroup with apparently stable, near-diploid chromosomes and
      stable microsatellites (MACS) also exists. These distinctions are important,
      partly because of their value in highlighting different pathways of
      carcinogenesis, and partly because of their direct relevance to prognosis. Study
      of early-onset cancer has often proved a fruitful resource for the identification
      of the nature and function of cancer susceptibility genes. In a study of
      colorectal cancer with stable microsatellite DNA, we describe 22 early-onset
      tumours (mean age=33), compared with 16 late-onset tumours (mean age=68). Both
      groups contained carcinomas with the MACS phenotype, characterized by near
      diploid DNA content, as defined by flow cytometry, and minimal chromosome arm
      deletion or amplification (six or less events per genome), determined by
      comparative genomic hybridization (CGH). Minimal chromosome imbalance correlated
      strongly with diploid DNA content (P<0.001). The proportion of MACS cancers was
      significantly greater in early-onset as compared to late-onset tumours (64 vs
      13%, P=0.005). Of the chromosome arm imbalances commonly observed in late-onset
      tumours, only 18q- was observed more than twice amongst the 14 early-onset MACS
      tumours. Seventy-nine per cent of these MACS tumours were located in the distal
      colon, and 69% were at advanced clinico-pathological stages (with lymph node or
      distant metastasis). A positive family history of colorectal or other cancers was
      elicited in seven patients in the MACS early-onset group, and one additional
      patient in this group had a metachronous ovarian cancer. The results suggest that
      MACS cancer may have a genetic basis different from either MIN or CIN, and
      further studies of these cancers may lead to discovery of new mechanisms of
      colorectal carcinogenesis and cancer susceptibility.

PMID- 11521199
TI  - Genes for human general transcription initiation factors TFIIIB, TFIIIB
      associated proteins, TFIIIC2 and PTF/SNAPC: functional and positional candidates
      for tumour predisposition or inherited genetic diseases?
AB  - TFIIIB, TFIIIC2, and PTF/SNAPC are heteromultimeric general transcription factors
      (GTFs) needed for expression of genes encoding small cytoplasmic (scRNAs) and
      small nuclear RNAs (snRNAs). Their activity is stimulated by viral oncogenes,
      such as SV40 large T antigen and Adenovirus E1A, and is repressed by specific
      transcription factors (STFs) acting as anti-oncogenes, such as p53 and pRb. GTFs
      role as final targets of critical signal transduction pathways, that control cell
      proliferation and differentiation, and their involvement in gene expression
      regulation suggest that the genes encoding them are potential proto-oncogenes or
      anti-oncogenes or may be otherwise involved in the pathogenesis of inherited
      genetic diseases. To test our hypothesis through the positional candidate gene
      approach, we have determined the physical localization in the human genome of the
      11 genes, encoding the subunits of these GTFs, and of three genes for proteins
      associated with TFIIIB (GTF3BAPs). Our data, obtained by chromosomal in situ
      hybridization, radiation hybrids and somatic cell hybrids analysis, demonstrate
      that these genes are present in the human genome as single copy sequences and
      that some cluster to the same cytogenetic band, alone or in combination with
      class II GTFs. Intriguingly, some of them are localized within chromosomal
      regions where recurrent, cytogenetically detectable mutations are seen in
      specific neoplasias, such as neuroblastoma, uterine leyomioma, mucoepidermoid
      carcinoma of the salivary glands and hemangiopericytoma, or where mutations
      causing inherited genetic diseases map, such as Peutz-Jeghers syndrome. Their
      molecular function and genomic position make these GTF genes interesting
      candidates for causal involvement in oncogenesis or in the pathogenesis of
      inherited genetic diseases.

PMID- 11521201
TI  - The C-terminus of mutant p53 is necessary for its ability to interfere with
      growth arrest or apoptosis.
AB  - The ability to suppress wild type p53-independent apoptosis may play an important
      role in the oncogenicity of p53 mutant proteins. However, structural elements
      necessary for this activity are unknown. Furthermore, it is unclear whether this
      mutant p53 mediated inhibition is specific to the apoptotic pathway or a more
      general suppression of the cellular response to stress. We observed that an
      unmodified C-terminus was required for the suppression of apoptosis by the p53
      135(Ala to Val) oncogenic p53 mutant. It was also required for the novel activity
      of G2 arrest suppression, the predominant response at low levels of genotoxic
      stress. These observations are consistent with a model whereby mutant p53
      suppressive activity is not specific to the apoptotic pathway, but rather
      increases the threshold of genotoxic stress needed for a DNA damage response to
      occur. Furthermore, these observations indicate that it may be possible to
      selectively kill mutant p53 expressing cells based on the lower sensitivity of
      their growth arrest response.

PMID- 11521200
TI  - Expression of the gut-enriched Kruppel-like factor (Kruppel-like factor 4) gene
      in the human colon cancer cell line RKO is dependent on CDX2.
AB  - Gut-enriched Kruppel-like factor (GKLF or KLF4) is a zinc finger-containing,
      epithelial-specific transcription factor, that functions as a suppressor of cell
      proliferation. We previously showed that GKLF expression is decreased in
      intestinal and colonic adenomas, respectively, from multiple intestinal neoplasia
      (Min) mice and familial adenomatous polyposis (FAP) patients. This study shows
      that GKLF is induced upon activation of the adenomatous polyposis coli (APC)
      gene. However, among several human colon cancer cell lines surveyed, expression
      of GKLF is lowest in RKO, a line with wild-type APC and beta-catenin. RKO
      contains a mutated allele that encodes the putative tumor suppressor homeodomain
      protein, CDX2. We show that wild-type CDX2 activates the GKLF promoter and that
      the mutated CDX2 has a dominant negative effect on wild-type function. Our
      results may help explain the exceedingly low levels of GKLF expression detected
      in this cell line, which may in turn contribute to the tumor phenotype.

PMID- 11521202
TI  - The Brn-3a transcription factor plays a key role in regulating the growth of
      cervical cancer cells in vivo.
AB  - The cellular Brn-3a transcription factor is known to activate transcription of
      the genes encoding the human papilloma virus E6 and E7 proteins and is over
      expressed in women with cervical neoplasia. We show that cervical cell lines with
      reduced Brn-3a expression show a greatly reduced ability to form tumours in nude
      mice compared to control cells and also show reduced expression of the HPV E6 and
      cellular Bcl-2 oncogenes. These effects are also observed in cervical cells over
      expressing the related Brn-3b factor, which is known to antagonize activation of
      HPV gene expression by Brn-3a. These results demonstrate, for the first time,
      that inhibition of Brn-3a expression or enhanced Brn-3b expression can inhibit
      cervical cell-derived tumour growth in vivo as well as in vitro. Hence they
      establish Brn-3a as a key factor in cervical tumorigenesis and as a potential
      therapeutic target in human cervical neoplasia.

PMID- 11521203
TI  - Tuberous sclerosis causing mutants of the TSC2 gene product affect proliferation
      and p27 expression.
AB  - The autosomal dominant disease tuberous sclerosis (TSC) is caused by mutations in
      either TSC1 on chromosome 9q34, encoding hamartin, or TSC2 on chromosome 16p13.3,
      encoding tuberin. TSC is characterized by hamartomas that occur in many organs of
      affected patients and these have been considered to likely result from defects in
      proliferation control. Although the true biochemical functions of the two TSC
      proteins have not been clarified, a series of independent investigations
      demonstrated that modulated hamartin or tuberin expression cause deregulation of
      proliferation/cell cycle in human, rodent and Drosophila cells. In support of
      tuberin acting as a tumor suppressor, ectopic overexpression of TSC2 has been
      shown to decrease proliferation rates of mammalian cells. Furthermore,
      overexpression of TSC2 has been demonstrated to trigger upregulation of the
      cyclin-dependent kinase inhibitor p27. We report that three different naturally
      occurring and TSC causing mutations within the TSC2 gene eliminate neither the
      anti-proliferative capacity of tuberin nor tuberin's effects on p27 expression.
      For the first time these data provide strong evidence that deregulation of
      proliferation and/or upregulation of p27 are not likely to be the primary/only
      mechanisms of hamartoma development in TSC. These results demand reassessment of
      previous hypotheses of the pathogenesis of TSC.

PMID- 11521204
TI  - Evidence for oligoclonality and tumor spread by intraluminal seeding in
      multifocal urothelial carcinomas of the upper and lower urinary tract.
AB  - Multifocality and recurrence of urothelial carcinoma may result from either the
      field effect of carcinogens leading to oligoclonal tumors or monoclonal tumor
      spread. Previous molecular studies, favoring the monoclonality hypothesis, are
      mostly limited to the urinary bladder. We investigated genetic alterations in a
      total of 94 synchronous or metachronous multifocal tumors from 19 patients with
      at least one tumor both in the upper and lower urinary tract. Loss of
      heterozygosity (LOH) was determined using eight markers on chromosome 9 and one
      marker on 17p13 (p53). Microsatellite instability was investigated at six loci
      and protein expression of MSH2 and MLH1 was evaluated by immunohistochemistry. In
      addition, exons 5-9 of the p53 gene were sequenced. Deletions at chromosome 9
      were found in 73% of tumors and at 17p13 in 18% of tumors. There was no
      significant difference in the frequency of LOH in the upper and lower urinary
      tract. Deletions at 9p21 were significantly correlated with invasive tumor
      growth. The pattern of deletion revealed monoclonality of all tumors in nine
      patients. In five patients there were at least two tumor clones with different
      genetic alterations. In four of these patients the different clones occurred in
      the bladder and subsequently in the ureter and renal pelvis. All four patients
      with p53 mutations revealed identical mutations in all tumors. Thus, multifocal
      urothelial carcinomas are frequently monoclonal, whereas others show
      oligoclonality, providing molecular evidence for field cancerization.
      Intraluminal tumor cell seeding appears to be an important mechanism of
      multifocal occurrence and recurrence of urothelial carcinomas.

PMID- 11521206
TI  - Inherited disorders of cholesterol biosynthesis.
AB  - Defects of cholesterol biosynthesis comprise a heterogeneous group of disorders,
      most of which have only been recently described and more are likely to follow in
      the near future. Mevalonic aciduria (MVA) and hyperimmunoglobulinemia D syndrome
      (HIDS) are due to allelic defects in mevalonate kinase, an enzyme located
      proximally in the pathway of cholesterol and nonsterol isoprene biosynthesis.
      Clinically, patients affected with these disorders present with recurrent febrile
      attacks. This is the only manifestation in most patients with HIDS, and, in the
      case of classical mevalonic aciduria, is part of a severe multisystemic disease,
      including malformations, severe failure to thrive and neurological abnormalities.
      The other recognized defects of cholesterol biosynthesis are due to enzyme
      defects located distally in the pathway beyond the branching points of nonsterol
      isoprene biosynthesis and solely affecting cholesterol biosynthesis. Patients
      with these disorders all present with complex malformation syndromes involving
      different organ systems. The main characteristics of CHILD syndrome and Conradi
      Huenermann syndrome are skeletal defects and ichthyosiform skin involvement.
      Smith-Lemli-Opitz syndrome and desmosterolosis are generalized malformation
      syndromes involving many different organs including the central nervous
      system.The diagnosis of MVA and HIDS is based on determination of mevalonic acid
      in urine followed by determination of enzyme activity, whereas the search for the
      distally located defects of cholesterol biosynthesis requires sterol analysis in
      blood or tissues by GCMS. Rational therapeutic approaches have been described for
      HIDS, MVA and Smith-Lemli-Opitz syndrome.

PMID- 11521207
TI  - Cause of progression in Duchenne muscular dystrophy: impaired differentiation
      more probable than replicative aging.
AB  - Replicative aging of myogenic cells (satellite cells) owing to enhanced myofiber
      turnover is a common explanation of the progression of Duchenne muscular
      dystrophy (DMD). This hypothesis has been reexamined recently by telomere length
      measurements in dystrophic tissue. We evaluate the controversial results of these
      studies. We also review a large body of in vitro, animal (mdx), and patient data
      which indicate that impaired differentiation, but not replicative aging, is the
      leading cause of progression in DMD. We recommend in vivo investigations of cell
      kinetics in DMD muscle, as well as telomere length and telomerase analyses of DMD
      satellite cells in vitro for a definite judgement of the replicative aging
      hypothesis. Analogous investigations were helpful in AIDS research where
      replicative aging was embraced as a simple explanation of the paradigmatic CD4
      lymphocyte decline but had to be rejected in favour of more complex models of
      disturbed lymphocyte homeostasis and regeneration. The question of replicative
      aging versus impaired differentiation is relevant for the understanding of
      therapeutic failures and the design of new strategies. Impaired differentiation
      is compatible with the failure of myoblast transfer in DMD and calls for further
      studies on the myofiber environment. Replicative aging, on the other hand, could
      possibly be treated by telomerase gene delivery.

PMID- 11521208
TI  - Long-term outcome in children with congenital unilateral facial nerve palsy.
AB  - During a 20-year period (1980 - 1999) 12 children with isolated congenital
      unilateral facial nerve palsy were seen at our hospital. The only child delivered
      by forceps made a full recovery from his palsy within two months, whereas
      functional improvement in patients with non-traumatic delivery was generally
      poor. In two patients the palsy affected predominantly the upper periocular
      region. In 10 children the lower facial region seemed to be mainly involved.
      Cognitive outcome was within normal limits, with one exception. Conventional
      neuroimaging was not contributory to the understanding of the pathogenetic
      mechanisms. We conclude that the majority of congenital unilateral facial nerve
      palsies are not of traumatic origin and carry a poor functional prognosis.

PMID- 11521209
TI  - Audiometric abnormalities in children with Gaucher disease type 3.
AB  - Exogenous enzyme replacement therapy achieves satisfactory biomedical correction
      in Gaucher type 1 disease and may halt or reverse neurological progression in
      type 3, while it does not appear to influence the outcome in type 2. In view of
      the therapeutic possibilities, early detection and monitoring of type 3 Gaucher
      disease, as well as evaluation of the effectiveness of enzyme therapy on
      neuronopathic involvement is necessary. The objective of this study was to
      evaluate the extent of brainstem disease in children with proven Gaucher type 3,
      by means of an audiological test battery. We studied 9 patients with Gaucher type
      3 disease. The tests included baseline audiometric tests, as well as auditory
      brainstem evoked responses (ABR), acoustic reflexes and medial olivo-cochlear
      suppression by contralateral noise tests, that involve overlapping but not
      identical efferent and afferent pathways and brainstem structures. We found a
      constellation of abnormalities including bilaterally raised acoustic reflexes,
      poor medial olivo-cochlear suppression, and very poor brainstem evoked
      potentials. These abnormalities could be due to a single lesion in the
      dorsomedial brainstem, or to multiple lesions, and further study is needed to
      clarify this issue. Combined audiological tests may provide information on the
      severity of the neurological involvement and should therefore be part of a
      standard assessment for the diagnosis as well as for long term neurological
      monitoring of Gaucher type 3 patients.

PMID- 11521210
TI  - Autosomal recessive spastic ataxia of Charlevoix-Saguenay in two unrelated
      Turkish families.
AB  - Autosomal recessive spastic ataxia of Charlevoix-Saguenay is an early onset form
      of hereditary spastic paraplegia with a peculiar clinical presentation. In
      addition to cerebellar findings which manifest first with ataxic gait in early
      life and spasticity, on an evolutionary basis, there is axonal neuropathy,
      prominent myelinated fibers in the optic fundus, and evidence of cerebellar
      atrophy that can be detected by cranial MRI. Intelligence is usually normal,
      however lower IQs have also been documented. This disorder mainly originates from
      the Charlevoix-Saguenay region of Quebec. Here, we report two Turkish families
      linked to the disease locus on chromosome 13 q12. There was homozygosity and
      segregation of disease haplotypes in both families. This form of spastic ataxia
      may be more common than originally presumed.

PMID- 11521211
TI  - Fetal nucleated red blood cell counts in peripheral blood of mothers bearing Down
      syndrome fetus.
AB  - Currently, prenatal detection of Down syndrome and other most common aneuploidies
      relies on invasive procedures such as amniocentesis and villocentesis, and on non
      invasive screening tests such as second trimester maternal serum screening
      (Triple test), and first trimester screening (ULTRA-screen). However, it well
      known that invasive techniques carry a small risk of fetal loss, while both
      Triple test and ULTRA-screen are not diagnostic, may miss from 15 - 40 % of cases
      of Down syndrome, in addition to having a 5 - 8 % rate of false-positives. We now
      report clear evidence that the number of fetal nucleated red blood cells (FNRBCs)
      in the maternal circulation is remarkably higher in pregnant women carrying
      aneuploid fetuses, especially in cases of Down syndrome. These results are in
      agreement with the findings of other investigators using different methods, and
      suggest that the number of FNRBCs present in the maternal blood sample could be
      used as additional marker, in concert with existing screening tests, to improve
      non-invasive detection of Down syndrome, and other most common aneuploidies.

PMID- 11521212
TI  - Respiratory chain deficiency in Alpers syndrome.
AB  - Alpers syndrome is a progressive encephalopathy of early onset, characterized by
      rapid and severe developmental delay, intractable seizures and liver involvement
      in a previously healthy child. Here, we report on respiratory chain enzyme
      deficiency in the liver of four unrelated children presenting with epileptic
      encephalopathy and liver involvement diagnosed as Alpers syndrome. Interestingly,
      oxidative phosphorylation in skeletal muscle was normal in 4/4 and blood and CSF
      lactate in 3/4 patients. Liver involvement had a late clinical onset in patients
      with previously isolated epileptic encephalopathy. Based on these observations,
      we suggest 1. to give consideration to respiratory chain deficiency in the
      diagnosis of severe epileptic encephalopathy in childhood, even when no clinical
      or biological evidence of liver involvement or lactic acidosis is noted, and 2.
      to investigate the respiratory chain in a needle biopsy of the liver in children
      with epileptic encephalopathy prior to valproate administration if biochemical
      indications for respiratory chain disease or hepatic disturbance are noted, as
      this drug is believed to occasionally trigger hepatic failure and fatal outcome.

PMID- 11521213
TI  - Report of eight cases of occipital dermal sinus: an update, and MRI findings.
AB  - OBJECTIVE: We report our experience with 8 patients who were ultimately diagnosed
      as having occipital dermal sinuses. Clinical presentation, imaging findings and
      outcome are discussed, along with a review of the literature. STUDY DESIGN: In
      eight patients with occipital dermal sinuses, we retrospectively collected the
      following data: time to diagnosis, presenting signs, dermal anomalies, location
      of bone defects, intraparenchymal extension, surgical techniques and clinical
      outcome. Conventional radiography was performed in all patients; computerized
      tomography (CT) scans and magnetic resonance imaging (MRI) in all but two.
      RESULTS: Time to diagnosis ranged from 3 months to 9 years. Presenting symptoms
      were: infection of a cutaneous mass (n = 4), occipital mass (n = 2), intracranial
      hypertension related to intra-cerebral abscess (n = 2). In all patients, dermal
      sinus was located near the external protuberance of the occipital bone. In all
      patients but one, a cutaneous orifice was associated. Other cutaneous anomalies
      were: hairy nevus (n = 2) and subcutaneous cysts (n = 4). One patient had
      associated cranio-facial malformations. Plain skull films revealed linear bony
      defects in all cases but one; CT scans revealed linear bony defects in all cases,
      osteitis and intra-parenchymal abscesses if present but they did not allow the
      delineation of the sinus tract. MRI performed in six patients allowed a better
      appreciation of the malformation revealing intracranial abscess (n = 1), the
      sinus tract (n = 2), inclusion cysts (n = 2), and associated venous anomalies (n
      = 1). Surgery was performed in all patients: a complete removal of the dermal
      sinus was obtained in all patients but one; inclusion cysts were found in six
      patients. Total recovery without sequelae was obtained in all patients, except
      one who suffered from developmental delay and a polymalformative syndrome.
      CONCLUSIONS: In newborns, a meticulous visual exploration of the midline skin
      along the craniospinal axis is necessary to detect congenital dermal
      abnormalities. Early surgery is required to prevent severe intracranial
      infection. MRI could help to determine the surgical approach by delineation of
      the sinus tract, its extension into deeper tissues and its association with
      cysts, abscesses or venous anomalies.

PMID- 11521214
TI  - Functional MRI in a 6-year-old boy with unilateral cortical malformation:
      concordant representation of both hands in the unaffected hemisphere.
AB  - Functional magnetic resonance imaging (fMRI) was performed in a 6-year-old boy
      with a complex malformation of the right hemisphere who suffered from pharmaco
      refractory epilepsy. Clinical examination revealed left-sided hemiparesis and
      marked mirror movements of the opposite hand both during paretic and non-paretic
      hand movements. Functional MRI of repetitive unimanual grasping demonstrated that
      the two hands share a common cortical representation located in the central motor
      region of the unaffected left hemisphere. The affected right hemisphere did not
      show any activation during either task. This case study demonstrates the
      feasibility and usefulness of motor fMRI in young children before they undergo
      epilepsy surgery.

PMID- 11521215
TI  - Rett syndrome in a boy with a 47,XXY karyotype confirmed by a rare mutation in
      the MECP2 gene.
AB  - Rett syndrome (RTT) is an X-linked condition which affects almost exclusively
      females. Here we report the first case of RTT syndrome in a boy with an XXY
      chromosomal constitution. Mutation analysis of the MECP2 gene in the affected
      patient revealed a 423 C-->G substitution in exon 4, resulting in a new stop
      codon (Y141 X). This change was not present in both his parents or in his older
      sister. Taking into account the incidence of both RTT syndrome as well as of
      Klinefelter syndrome, the probability for the simultaneous occurrence of these
      two events is very low (about approximately 1 in 10 to 15,000,000 births).
      However, the recent identification of mutations in the MECP2 gene in affected
      males indicates that screening of the MECP2 gene should be considered also in
      males with severe mental retardation (MR) in whom the most common forms of MR
      have been excluded.

PMID- 11521216
TI  - Progressive elevation of liver enzymes in a child treated with sulthiame.

PMID- 11521217
TI  - Cyclin-dependent kinase inhibitors--a novel class of prognostic indicators.

PMID- 11521218
TI  - Reduced p21(WAF1/CIP1) expression is an early event in gallbladder carcinogenesis
      and is of prognostic significance for patients with carcinomas of the
      gallbladder.
AB  - The molecular basis underlying the development and progression of gallbladder
      carcinoma (GBC) remains poorly understood. To evaluate the roles of
      p21(WAF1/CIP1) and p53 in gallbladder carcinogenesis and to assess their
      prognostic significance for patients with GBC, we used immunohistochemistry to
      examine the expression of p21(WAF1/CIP1) and p53 protein in a series of
      surgically resected specimens, including normal epithelia, precancerous lesions
      adenoma, and dysplasia, and carcinomas of the gallbladder. Reduced p21(WAF1/CIP1)
      expression was frequently observed in carcinomas (18 of 37 lesions; 49%), and
      even in precancerous lesions adenomas (3 of 7; 43%) and dysplasias (5 of 5;
      100%). p53 overexpression was detected in 43% of the adenomas, 60% of the
      dysplasias and 57% of the carcinomas. There was an inverse relationship between
      p21(WAF1/CIP1) and p53 expression in GBCs (P =.01). Survival analysis indicated
      that reduced p21(WAF1/CIP1) expression was significantly associated with
      shortened disease-free and overall survival (P =.04 and.03, respectively) for
      patients with stages II to IV GBCs. These observations suggest that reduced
      p21(WAF1/CIP1) expression and p53 overexpression contribute to GBC from an early
      stage and that determination of p21(WAF1/CIP1) expression in surgically resected
      specimens would add prognostic information to conventional pathologic
      examinations for patients with advanced-stage GBC.

PMID- 11521219
TI  - Expression of p27(KIP1) and p21(WAF1/CIP1) in primary hepatocellular carcinoma:
      clinicopathologic correlation and survival analysis.
AB  - To investigate the possible roles of p27(KIP1) and p21(WAF1/CIP1), inhibitors of
      cyclin-dependent kinases, in hepatocellular carcinoma (HCC), we examined
      p27(KIP1) and p21(WAF1/CIP1) expression in primary HCC with immunohistochemistry
      and Northern blot hybridization and correlated the results with clinicopathologic
      features and survival. With immunohistochemistry, positive staining for p27(KIP1)
      and p21(WAF1/CIP1) protein was found in 54.3% and 63.8% of HCCs, respectively.
      Both p27(KIP1) and p21(WAF1/CIP1) scores of the tumors were significantly higher
      than those of the corresponding nontumorous livers (P <.0001 and.009,
      respectively). Higher levels of p27(KIP1) were associated with a lower incidence
      of direct liver invasion (P =.021) and, less significantly, with a low incidence
      of multiple tumor nodules (P =.056). Patients whose tumors had higher p27(KIP1)
      protein scores had longer disease-free survival (P =.011). For p21(WAF1/CIP1), in
      contrast to the overexpression of the p21(WAF1/CIP1) protein in HCC, the relative
      amounts of p21(WAF1/CIP1) messenger RNA (mRNA) in the tumors were found to be
      reduced compared with those of the nontumorous livers (P =.039). In conclusion,
      p27(KIP1) and p21(WAF1/CIP1) proteins were frequently overexpressed in HCC.
      Longer disease-free survival rates were seen in patients whose tumors had higher
      p27(KIP1) expression. The accumulation of p21(WAF1/CIP) protein in the presence
      of a reduced mRNA level suggests probable posttranslational protein
      stabilization, and the reduced transcription of p21(WAF1/CIP) may represent a
      form of dysfunction of cyclin-dependent kinase inhibitor involved in
      hepatocarcinogenesis.

PMID- 11521220
TI  - Atypical ductal hyperplasia and ductal carcinoma in situ of the breast associated
      with perineural invasion.
AB  - Perineural invasion is a histologic feature usually diagnostic of invasion in
      malignancies. In the breast, however, it has been associated with benign lesions
      such as sclerosing adenosis (SA), complex sclerosing lesion/radial scar (CSL/RS),
      and ductal carcinoma in situ (DCIS). This article describes perineural invasion
      associated with atypical ductal hyperplasia (ADH), florid hyperplasia without
      atypia (FH), and DCIS. All cases with a diagnosis of perineural invasion were
      selected from a series of 10,000 breast consult cases. Invasive mammary
      carcinomas were excluded. Fourteen cases of perineural invasion were found and
      associated with the following diagnoses: ADH (5), DCIS (3), FH (5), and ductal
      adenoma (1). Nine cases developed in CSL/RS, 4 cases in SA, and 1 case in a
      previous biopsy site of ductal adenoma; lesions were all less than 3 mm. The
      glands involving nerves showed cytologic and architectural features of the
      adjacent ADH, DCIS, and FH. Immunostaining for protein gene product (PGP) 9.5
      marked nerves, and smooth muscle actin antibody highlighted the myoepithelial
      cells around glands. Perineural invasion seen in association with DCIS and ADH,
      in a background of CSL/RS and SA, may pose difficulty in diagnosis, especially in
      small biopsy specimens. It should be assessed with care to avoid
      misinterpretation as invasive mammary carcinoma.

PMID- 11521221
TI  - Reduced expression of dystroglycan in breast and prostate cancer.
AB  - Cellular interactions with the extracellular matrix are an important factor in
      the development and progression of many types of cancer. Dystroglycan is a cell
      surface receptor for several extracellular matrix proteins and plays a central
      role in the formation of basement membranes in tissues. Because abnormalities in
      the structure and function of basement membranes are hallmarks of metastatic
      disease, we examined the status of dystroglycan expression in prostate and breast
      tumors. In 15 cases of surgically resected prostate cancer, we noted reduced
      expression of dystroglycan as judged by intensity of immunohistochemical
      staining. This reduction was most pronounced in high-grade disease. We found
      similar results in 6 cases of mammary ductal adenocarcinoma, suggesting that
      reduced expression of dystroglycan may be a conserved feature of epithelial
      neoplasia. These data suggest that reduced expression of dystroglycan in prostate
      and breast cancers may lead to abnormal cell-extracellular matrix interactions
      and thus contribute to progression to metastatic disease.

PMID- 11521222
TI  - Sertoli-stromal cell tumor of the ovary: immunohistochemical, ultrastructural,
      and genetic studies.
AB  - The Sertoli-stromal cell tumor (SSCT) of the ovary shows a histologic resemblance
      to developing or adult testes and is often associated with virilization caused by
      tumor-produced androgenic hormone. In spite of the unique manifestation of SSCT,
      detailed characteristics of this tumor are still obscure. The mechanism by which
      SSCT occurs has not yet been determined. Six SSCTs were studied
      immunohistochemically, ultrastructurally, and by polymerase chain reaction (PCR)
      for the presence of sex-determining region Y (SRY) gene and the X chromosome
      activation state. Immunohistochemically, Sertoli-like cells of SSCT were positive
      not only for alpha-inhibin but also low-molecular-weight cytokeratin. In control
      testes, the expression of alpha-inhibin and cytokeratin was limited to a Sertoli
      cell component and rete testis, respectively. Ultrastructurally, tumor cells
      composing hollow tubules had an elongated nucleus with deep indentation and
      annulate lamellae, which are characteristic structures of mature Sertoli cells.
      In addition, they had studded microvilli on the apical surface and frequent
      desmosomes, which are structures noted in the cells of rete testis.
      Histologically, tumor cells of hollow tubules sometimes pouted into the lumen, as
      did the cells of tubulae rete, entrance into rete testis from seminiferous
      tubules. All of these findings indicate that some tumor cells of a SSCT show
      simultaneous differentiation into both Sertoli cells and cells of rete testis.
      SRY gene was not detected in any cases, and the X chromosome activation pattern
      was the same as that of the female control.

PMID- 11521223
TI  - Expression of dendritic cells in ovarian tumors correlates with clinical outcome
      in patients with ovarian cancer.
AB  - Dendritic cells (DCs) are the most potent antigen-presenting cells and are
      thought to reflect the interaction between the host immune system and tumor
      cells. In a retrospective study, we analyzed the presence of DCs and memory
      lymphocytes in tumor biopsy specimens of 18 patients with ovarian cancer. These
      patients were followed up for 10 to 37 months. Within this period, 9 patients had
      no evidence of disease (NED, group A), and 9 patients had recurrence (group B).
      In group A, 5 cases were stage III, 1 was stage I, and 1 was stage II. In group
      B, 5 cases were stage III, 1 was stage III-IV, and 3 were stage IV. Our results
      show that the mean number of cells expressing the DC phenotype, HLA-DR(+)
      CD1a(+), in tumor biopsies was substantially higher in group A than in group B
      (HLA-DR(+): 37.8 +/- 18.2 v. 10.7 +/- 2.2, respectively; P <.005; CD1a(+): 9.5 +/
      11.3 v 2.1 +/- 3.7). On the other hand, the number of cells expressing the DC
      phenotype S-100 protein was substantially lower in group A than in group B (S
      100(+): 9.7 +/- 9.9 v 16.2 +/- 12.7), although the difference was not
      statistically significant. There was no difference in the number of tumor
      infiltrating CD45RO(+) cells between groups A and B (CD45RO(+): 39.1 +/- 28.5 v
      34.2 +/- 19.1). Our results show that the presence of relatively high numbers of
      defined DC subpopulations may have prognostic value in ovarian tumors.

PMID- 11521224
TI  - Expression of cell cycle regulators p57(KIP2), cyclin D1, and cyclin E in
      epithelial ovarian tumors and survival.
AB  - The search for new prognostic indicators is especially important in the diagnosis
      and treatment of ovarian cancer because clinicopathologic criteria currently used
      to predict survival are largely inadequate. We examined 2 groups of patients with
      epithelial ovarian cancer, 1 group of long-term survivors (>5 years), and 1 group
      of short-term survivors (<2 years) for levels of expression of the cell cycle
      regulators p57(KIP2), cyclin D1, and cyclin E and their relationship with
      survival. Our findings show that p57(KIP2) is not associated with prognosis, in
      contrast to p27(KIP1) expression, which is previously shown to be positively
      associated with long-term survival in univariate analysis (P =.001). Cyclin E
      expression, in contrast to cyclin D1 expression, is marginally associated with
      short-term survival in univariate analysis for a group of 53 women. Among the
      short-term survivors, 15 (65%) of 23 were positive for cyclin E expression,
      compared with only 11 (37%) of 30 long-term survivors (P = 0.054). This
      association remained significant (P =.04) in a logistic regression analysis
      adjusted simultaneously for performance status and extent of residual disease,
      the 2 strongest predictors of survival in our study. We also found a significant
      difference in the frequency of the cyclin E staining pattern between nonserous
      and serous ovarian tumor subtypes (P =.0002). Immunostaining for levels of cyclin
      E and p27(KIP1) expression may have potential as prognostic markers in the
      management of ovarian cancer.

PMID- 11521225
TI  - Adult-to-adult live donor liver transplantation: a short-term clinicopathologic
      study.
AB  - With the success of pediatric live donor liver transplantation (LDLT) and the
      continued shortage of cadaveric donors, adult-to-adult LDLT has been performed at
      some centers, including ours. We performed a detailed histologic review of all
      liver specimens obtained from 9 adult recipients at and after LDLT and correlated
      these findings with the patients' course and outcome. Five patients had
      histologic evidence of biliary tract pathology; 3 of 5 required surgical or
      radiologic intervention. The other 2 had clinically insignificant biliary
      disease. Diffuse hepatocytic hemorrhagic necrosis secondary to massive portal
      blood flow after portal venous revascularization resulted in graft failure and
      retransplantation in a single patient with severe preoperative portal
      hypertension. Two perioperative deaths were caused by sepsis and multiorgan
      failure (day 25) and generalized thrombosis related to factor V Leiden (day 6).
      The preoperative diagnosis, presence of portal vein thrombosis in the native
      liver, postoperative cholangiopathy, and subcapsular hemorrhagic necrosis in
      donor liver wedge biopsies did not affect the short-term outcome. In conclusion,
      biliary tract pathology is common after adult-to-adult LDLT but does not
      negatively affect graft or patient survival. Infrequent but catastrophic vascular
      complications related to portal hemodynamics or thrombosis can result in graft
      loss and/or patient death.

PMID- 11521226
TI  - Cholangiocytic apoptosis in chronic ductopenic rejection.
AB  - The significance of cholangiocytic apoptosis as a mechanism of ductopenia in
      liver rejection remains controversial. In a previous study, the presence but not
      the extent of ductal apoptosis was assessed by electron microscopy. Other
      previously published studies using an in situ hybridization method (in situ end
      labeling) produced conflicting results (no apoptosis v massive apoptosis). We
      studied 47 liver needle biopsies from 8 patients with chronic ductopenic
      rejection confirmed by pathologic examination of the failed grafts. These
      biopsies were performed because of graft dysfunction, during a period of several
      months before retransplantation, and they showed cholangiocytic injury with
      progressive ductal paucity. Terminal deoxynucleotidyl transferase-mediated
      deoxyuridine triphosphate-biotin nick-end labeling (TUNEL) was used to detect
      apoptosis (tissue digestion with proteinase K 20 microg/mL for 20 minutes). The
      interlobular bile ducts did not show labeling, even in lymphocytic cholangitis
      with obvious epithelial injury. However, there was minimal staining of ductular
      nuclei. Lymphocytic nuclei were also labeled. Apoptosis was not detectable in the
      vanishing interlobular bile ducts, even when more representative samples were
      studied and a more sensitive method was used. Unless apoptosis of cholangiocytes
      is an exceptionally rapid process escaping detection by conventional methods,
      ductopenia results mainly from ordinary, nonprogrammed cholangiocytic death.
      Apoptosis could still be involved in the pathogenesis of ductopenia by depleting
      cholangiocytic precursors, generally presumed to reside in ductules. This is a
      possible mechanism suggested by the following: (1) the established role of
      apoptosis in the homeostatic control of immature/progenitor cells, (2) the
      paucity of ductular proliferation in chronic rejection, (3) the previously
      reported decrease of ductular bcl-2 expression in rejection, and (4) the sporadic
      ductular TUNEL labeling seen in this study.

PMID- 11521227
TI  - Prognostic significance of the diameter of perineural invasion in radical
      prostatectomy specimens.
AB  - We assessed whether the quantification of cancer invasion into the perineural
      space influences the prognosis of patients treated with radical prostatectomy. We
      conducted a retrospective study of clinical and pathologic features in 640
      consecutive patients with clinical stage Tla-T3bNXM0 prostate cancer who were
      treated with radical retropubic prostatectomy by the same surgeon between 1989
      and 1995. None had received preoperative hormonal therapy or radiotherapy.
      Detailed pathologic analysis, including the presence and maximum diameter of
      perineural invasion (PNI), was performed by 2 pathologists. Treatment failure was
      defined as either a serum prostate-specific antigen (PSA) level > 0.4 ng/mL and
      rising or initiation of adjuvant therapy. The median follow-up time was 48 months
      (range, 1 to 111 months). Overall, PNI was detected in 477 patients (75%). The
      progression-free 5-year probability rate after prostatectomy for patients with
      PNI was 70% +/- 3% compared with 94% +/- 2% for patients without PNI (P <.001).
      The mere presence of PNI was not an independent predictor of progression in a Cox
      proportional hazards analysis when the other established prognostic factors
      (serum PSA level, pathologic stage, surgical margin, and tumor volume) were
      considered. However, the increasing diameter of the largest focus of PNI was
      strongly associated with other established prognostic factors and the probability
      of progression after radical prostatectomy. Although little adverse effect in
      patients with PNI < 0.25 mm was seen 5 years after surgery, those with a PNI
      diameter of 0.25 to 0.5 mm were significantly (P <.001) less likely to remain
      free of progression; only 36% of those with PNI of 0.5 to 0.75 mm (P <.001) and
      14% of those with PNI > or =0.75 mm (P =.002) were free of progression. In a Cox
      proportional hazard analysis, the PNI diameter was an independent predictor of
      prognosis. These results support that the measurement of the PNI diameter, easily
      recorded from prostatectomy specimens, could add important information to the
      prognosis of prostate cancer patients. Controversy regarding the significance of
      PNI may result from the lack of quantitative assessment of PNI in previous
      studies.

PMID- 11521228
TI  - Intraductal papillary components in invasive ductal carcinoma of the pancreas are
      associated with long-term survival of patients.
AB  - Most patients with pancreatic ductal carcinoma have a poor prognosis. However, in
      certain cases, 5-year survival can be achieved after surgical resection. Analysis
      of the pathologic findings associated with good survival rates will assist in
      identifying the optimum treatment. The clinicopathologic features of 67 patients
      who underwent surgical resection of ductal adenocarcinoma of the pancreas between
      1990 and 1996 were reviewed and correlated with survival rates. There were 42 men
      and 25 women, with a mean age of 62.1 years (range, 44 to 82 years). The mean
      greatest diameter of the tumor was 4.3 cm (range, 1.5 to 11 cm). Nineteen
      patients (29.4%) survived more than 3 years, and 9 (13.2%) survived more than 5
      years after surgical resection. The intraductal papillary component (IDPC) of the
      carcinoma was the main focus of the pathologic observations. IDPC was defined as
      intraductal papillary proliferative lesions seen in the tumor nodule with
      proliferative cells consistent with carcinomatous cellular atypia. IDPC was
      clearly present (++) in 24 patients and vaguely present (+) in 9 patients. Using
      the Mantel-Cox test, a statistically significant correlation was found between
      the presence of IDPC (either + or ++) and postoperative patient survival (P
      =.002). IDPC is a morphologic feature associated with longer patient survival and
      should be taken into consideration in assessing the pathway of tumor progression.

PMID- 11521229
TI  - Mast cell involvement in fibrodysplasia ossificans progressiva.
AB  - Fibrodysplasia ossificans progressiva (FOP) is a catastrophic genetic disorder of
      progressive heterotopic ossification associated with dysregulated production of
      bone morphogenetic protein 4 (BMP4), a potent osteogenic morphogen. Postnatal
      heterotopic ossification in FOP is often heralded by hectic episodes of severe
      post-traumatic connective tissue swelling and intramuscular edema, followed by an
      intense and highly angiogenic fibroproliferative mass. The abrupt appearance,
      intense size, and rapid intrafascial spread of the edematous preosseous
      fibroproliferative lesions implicate a dysregulated wound response mechanism and
      suggest that cells and mediators involved in inflammation and tissue repair may
      be conscripted in the growth and progression of FOP lesions. The central and
      coordinate role of inflammatory mast cells and their mediators in tissue edema,
      wound repair, fibrogenesis, angiogenesis, and tumor invasion prompted us to
      investigate the potential involvement of mast cells in the pathology of FOP
      lesions. We show that inflammatory mast cells are present at every stage of the
      development of FOP lesions and are most pronounced at the highly vascular
      fibroproliferative stage. Mast cell density at the periphery of FOP lesional
      tissue is 40- to 150-fold greater than in normal control skeletal muscle or in
      uninvolved skeletal muscle from FOP patients and 10- to 40-fold greater than in
      any other inflammatory myopathy examined. These findings document mobilization
      and activation of inflammatory mast cells in the pathology of FOP lesions and
      provide a novel and previously unrecognized target for pharmacologic intervention
      in this extremely disabling disease.

PMID- 11521230
TI  - Co-downregulation of cell adhesion proteins alpha- and beta-catenins, p120CTN, E
      cadherin, and CD44 in prostatic adenocarcinomas.
AB  - Cell adhesion molecule expression has been linked to disease outcome in prostatic
      adenocarcinomas (PACs). We evaluated the coordinated expression of catenin
      related proteins, E-cadherin, N-cadherin, and CD44s in PACs. Archival sections
      from 112 PACs were immunostained by an automated method (Ventana Medical Systems,
      Tucson, AZ) using monoclonal antibodies to alpha- and beta-catenins, p120CTN, E
      cadherin, N-cadherin, and CD44s proteins. Immunoreactivity was semiquantitatively
      scored, and results were evaluated for association between these markers.
      Staining results were also correlated with tumor grade, stage, ploidy,
      preoperative serum PSA, and postoperative biochemical disease recurrence.
      Decreased expression of alpha- and beta- catenins, p120CTN, E-cadherin, and CD44s
      proteins (range, 5% to 49%) was noted in PACs, and downregulation of each of
      these proteins correlated with high tumor grade (P =.02 to.0001). Although loss
      of E-cadherin and p120CTN each correlated with stage (E-cadherin, P =.02;
      p120CTN, P =.02) and ploidy (E-cadherin, P =.0001; p120CTN, P =.004),
      downregulation of CD44s correlated with ploidy (P =.002), serum PSA (P =.005),
      and postoperative disease recurrence (P =.02). N-cadherin was positive in only 5%
      of PACs and did not correlate with any prognostic parameters. alpha-Catenin
      downregulation correlated with decreased expression of E-cadherin (P =.0001).
      Additionally, decreased expression of each of these 2 proteins respectively
      correlated with loss of beta-catenin (P =.0001 and.004), p120CTN (P =.005
      and.001), and CD44s (P =.008 and.01). beta-Catenin expression levels correlated
      with p120CTN (P =.01). A trend for co-downregulation of CD44s and p120CTN and of
      CD44s and beta-catenin was observed. In conclusion, the significant association
      between decreased expression of various members of the CAM family of proteins
      supports their collective role in mediating cell-cell adhesion. Altered
      expression of these proteins may be of prognostic value in patients with prostate
      cancer.

PMID- 11521231
TI  - Altered global methylation of DNA: an epigenetic difference in susceptibility for
      lung cancer is associated with its progression.
AB  - Alterations in global DNA methylation have been observed in many cancers, but
      whether such alterations represent an epigenetic difference in susceptibility for
      the disease is unknown. The status of global DNA methylation also has not been
      reported in intact or specific types of cells involved in the carcinogenic
      process. To address these issues in lung carcinogenesis, we evaluated the status
      of global DNA methylation by using a monoclonal antibody specific for 5
      methylcytosine (5-mc) in randomly selected lung specimens of 60 cigarette smokers
      who developed squamous cell carcinoma (SCC) and 30 cigarette smokers who did not.
      5-mc immunostaining scores of DNA of SCC (0.61 +/- 0.42) and associated
      hyperplastic lesions (0.82 +/- 0.27) was significantly lower than those of DNA of
      histologically normal bronchial epithelial cells (0.99 +/- 0.52) and hyperplastic
      lesions (1.2 +/- 0.22) of noncancer specimens. The ratio of 5-mc scores between
      SCC and matched uninvolved bronchial epithelial cells was significantly
      associated with advanced stage and size of the tumor. The results suggest that
      alteration in global DNA methylation is an important epigenetic difference in
      susceptibility for the development of lung cancer. The reduced global DNA
      methylation in SCC compared with epithelial hyperplasia and its association with
      tumor size and disease stage is suggestive of its involvement in the progression
      of SCC. The results also indicate that normal methylation of DNA in epithelial
      hyperplastic lesions may prevent the transformation of these lesions to invasive
      cancer. If these results are confirmed, the status of DNA methylation in early
      lesions such as epithelial hyperplasia could be used to identify smokers who are
      at risk for the development of SCC.

PMID- 11521232
TI  - Relationship between Epstein-Barr virus and lymphoepithelioma-like carcinoma of
      the lung: a clinicopathologic study of 6 cases and review of the literature.
AB  - Lymphoepithelioma-like carcinoma (LELC) is a rare form of lung cancer, usually
      encountered in Chinese patients. Similar to nasopharyngeal carcinoma, LELC of the
      lung is strongly associated with Epstein-Barr virus (EBV) infection in Asian
      patients, but there is controversy over whether an association exists in patients
      from Western countries. To determine whether such a relationship exists, we
      retrospectively studied 6 cases of primary LELC of the lung, all of which were in
      Western patients. There were 4 men and 2 women, ranging in age from 49 to 75
      years. The tumors ranged from 1 to 4.5 cm in diameter. Four patients had stage I
      disease, 1 had stage IIb disease, and 1 had stage IIIa disease. All patients are
      alive without evidence of disease with a follow-up of 18 to 30 months. Formalin
      fixed, paraffin-embedded tissue was stained with hematoxylin-eosin for routine
      evaluation and immunostained for keratin and leukocyte common antigen (LCA). LCA
      staining was performed to exclude large-cell lymphoma. Immunoperoxidase staining
      (1:500 clone CS1-4; Dako, Carpinteria, CA) and in situ hybridization were
      performed to detect EBV. Tumors consisted of solid nests of undifferentiated
      tumor cells in a syncytial arrangement surrounded by heavy lymphoplasmacytic
      infiltrate. Tumor cells stained positively for keratin but negative for LCA. All
      6 cases were negative for EBV, suggesting no association between EBV and LELC in
      the Western population.

PMID- 11521233
TI  - Keratin 1 expression in endothelia and mesenchymal tumors: an immunohistochemical
      analysis of normal and neoplastic tissues.
AB  - Keratin polypeptides of the nonhair type, numbered 1 through 20 in the Moll
      catalog, are selectively expressed in normal and neoplastic tissues. Keratin 1
      (K1), the highest-molecular-weight keratin (67 kd), was generally considered
      specific for keratinizing squamous epithelia. However, recent studies have shown
      that it is an integral component of the multiprotein kininogen receptor of
      endothelial cells. A library of formalin-fixed, paraffin-embedded tissue samples
      was evaluated immunohistochemically (avidin-biotin peroxidase complex method) for
      K1 expression using a specific monoclonal antibody (Novocastra clone 34betaB4).
      The study group included a wide variety of normal tissues and 541 tumors of
      epithelial or mesenchymal derivation. The specificity of the antibody to K1 was
      verified in normal epithelial tissues, where the staining was essentially limited
      to the epidermis and Hassal corpuscles of the thymus and focally to other
      squamous epithelia. Among carcinomas, it was essentially limited to keratinizing
      squamous carcinomas. It was also regularly found in endothelial cells of normal
      capillaries, veins, and arteries. Capillary, cavernous, and venous hemangiomas
      often had endothelia with K1 positivity. Among the malignant vascular tumors,
      epithelioid hemangioendotheliomas were consistently positive (8 of 8). However,
      angiosarcomas had more variable expression (59 of 81 were positive), with well
      differentiated tumors generally having greater reactivity than poorly
      differentiated examples. Mesenchymal tumors with K1 expression included
      schwannomas (10 of 16), epithelioid sarcomas (26 of 37), and synovial sarcomas
      (19 of 68). In the last 2 tumor types, K1 reactivity was detected in both
      epithelioid and spindled neoplastic populations. In addition to its specificity
      for keratinizing squamous epithelia, K1 can be immunohistochemically detected in
      normal vascular endothelial cells and a spectrum of vascular tumors. However, its
      expression in poorly differentiated vascular tumors is variable, suggesting that
      this marker is poorly conserved in highly transformed endothelia. The unexpected
      K1 immunoreactivity in nonvascular soft tissue tumors, such as synovial sarcoma,
      epithelioid sarcoma, and schwannomas, requires further study.

PMID- 11521234
TI  - Pigmented intraosseous odontogenic carcinoma of the maxilla: a pediatric case
      report and differential diagnosis.
AB  - We report a pigmented intraosseous odontogenic carcinoma of the maxilla occurring
      in a 6-year-old Japanese boy. Grossly, the tumor showed solid, gray-yellow, and
      markedly pigmented appearance. Histology showed neoplastic growths of atypical
      epithelial cells that occasionally contained melanin pigments. Melanocytes with
      dendritic processes were often found in the tumor cell clusters, and solitary or
      aggregated melanophages were scattered within the dense fibrovascular stroma. The
      tumor cells were diffusely positive for cytokeratins and epithelial membrane
      antigen, and focally positive for vimentin, neuron specific enolase,
      neurofilament protein, carcinoembryonic antigen, and amelogenin. Ultrastructural
      studies showed well-developed intercellular junctions, mainly desmosomes, and
      glycogen particles. In addition, some tumor cells contained melanosomes and/or a
      few neurosecretory granules. We consider that the present tumor suggests a close
      association of ectoderm, mesenchyma, and neuroectoderm in embryogenesis of the
      tooth, and can raise a diagnostic confusion with melanotic neuroectodermal tumor.

PMID- 11521235
TI  - Aggressive uterine sarcoma with rhabdoid features: diagnosis by peritoneal fluid
      cytology and absence of INI1 gene mutation.
AB  - We report a primary uterine sarcoma with classic histologic, immunohistochemical,
      and ultrastructural features of a malignant extrarenal rhabdoid tumor (MERT). It
      arose in a 71-year-old woman who presented with postmenopausal bleeding, ascites,
      and a right pelvic mass. Malignant cells with rhabdoid morphology were identified
      by cytologic examination of the peritoneal fluid. Exploratory laparotomy revealed
      a 10-cm right adnexal mass and disseminated peritoneal tumor. Pathologic study
      showed diffuse expansion of the endometrial stroma by rhabdoid-like cells with
      transmural infiltration of the myometrium and extensive involvement of uterine
      serosa and right ovary by tumor. Neoplastic cells were immunoreactive for
      vimentin, cytokeratin, and epithelial membrane antigen, and cytoplasmic whorls of
      intermediate filaments were observed by electron microscopy. Fluorescence in situ
      hybridization (FISH) studies with chromosome 22-specific probes showed no loss of
      the INI1 gene, and no coding sequence mutation was identified.

PMID- 11521236
TI  - Are there histopathologic characteristics particular to fulminant hepatic failure
      caused by human herpesvirus-6 infection? A case report and discussion.
AB  - An 8-month-old boy was admitted to a neighboring hospital for severe liver
      dysfunction and drowsiness 4 days after a diagnosis of exanthem subitum. A
      diagnosis of fulminant hepatic failure was made, and liver biopsy was performed
      during the acute stage. The presence of human herpesvirus-6 variant B (HHV-6B)
      DNA was shown in liver tissue by polymerase chain reaction (PCR) and in the
      endothelium of the portal vein by in situ hybridization (ISH). Histologic
      examination showed microvesicular steatosis resembling that of Reye's syndrome,
      even though aspirin had not been prescribed. We considered HHV-6 to be the
      causative agent in this case and report what is perhaps the first precise
      histologic description of fulminant hepatic failure caused by HHV-6.

PMID- 11521237
TI  - Intrathyroidal water-clear cell parathyroid adenoma: a case report.
AB  - Adenomas of the parathyroid gland, the majority of which contain mixed cell
      populations, are the most frequent cause of primary hyperparathyroidism.
      Parathyroid adenomas composed exclusively of water-clear cells are exceptionally
      rare. Until now, only 2 cases have been reported in English literature. We report
      a water-clear cell adenoma of the parathyroid gland in an intrathyroidal
      position, which has not been described previously according to our knowledge.

PMID- 11521238
TI  - Thanatosomes and cardiomyocyte apoptotic bodies.

PMID- 11521241
TI  - Pathogenesis of Histoplasma capsulatum.
AB  - Histoplasma capsulatum is well adapted to be infectious and pathogenic for
      humans. As a soil fungus with no known requirement for interacting with a
      mammalian host as part of an obligate lifecycle, its plethora of strategies for
      successful pathogenesis is particularly remarkable. These features include the
      dimorphic mold-yeast transition, entry into host macrophages, subcellular
      localization, intracellular survival and proliferation during active infection,
      and persistence during clinically inapparent infection with the capacity for
      reactivation. To thrive within the harsh environment of a professionally
      phagocytic and antimicrobial host cell, H. capsulatum displays mechanisms for
      modulating its microenvironmental pH level, resisting host reactive oxygen and
      nitrogen intermediates and degradative enzymes, and withstanding nutrient
      starvation conditions, including acquisition of iron and calcium and biosynthesis
      of nucleic acid precursors. Attention has been focused on identifying virulence
      associated phenotypic traits and genes that are differentially expressed under
      relevant conditions, such as yeast morphotype-specific genes and genes that are
      up-regulated during infection. These studies, together with the increasing
      ability to perform molecular genetic manipulations in this fungus, may yield
      novel antifungal drug or vaccine targets as well as elucidating pathogenic
      mechanisms.

PMID- 11521242
TI  - Cell-mediated immunity to Histoplasma capsulatum.
AB  - Histoplasma capsulatum is a facultative intracellular pathogen, and the causative
      agent of the most common systemic fungal infection. Over the past several years,
      many new insights have been learned concerning the biology, biochemistry, and
      molecular genetics of this microorganism. This review focuses on the immunology
      of host defense against H. capsulatum yeasts with emphasis on the development of
      cell-mediated immunity, and the strategies used by the fungus to survive and
      multiply within macrophages.

PMID- 11521243
TI  - The epidemiology of histoplasmosis: a review.
AB  - Histoplasmosis is the most common endemic mycosis in the United States and has
      recently emerged as an important opportunistic infection among human
      immunodeficiency virus (HIV)-infected persons living in areas where it is
      endemic. In this article, we describe the epidemiologic and ecologic features of
      histoplasmosis, highlighting the implications for prevention. Surveillance and
      education of the public and health care providers are needed to determine the
      disease burden of histoplasmosis. Development of better diagnostic tests for
      detection of disease in humans and of the organism in the environment will help
      in designing better prevention strategies.

PMID- 11521244
TI  - Mediastinal fibrosis.
AB  - Mediastinal fibrosis is the least common, but the most severe, late complication
      of histoplasmosis. It should be differentiated from the many other less-severe
      mediastinal complications of histoplasmosis, and from other causes of mediastinal
      fibrosis. Posthistoplasmosis mediastinal fibrosis is characterized by invasive,
      calcified fibrosis centered on lymph nodes, which, by definition, occludes major
      vessels or airways.

PMID- 11521245
TI  - Laboratory diagnosis of histoplasmosis: update 2000.
AB  - Histoplasmosis is a common infection in endemic regions of North and Latin
      America, causing a broad spectrum of clinical findings. Although acute pulmonary
      infection, chronic pulmonary, and progressive disseminated histoplasmosis are the
      most commonly recognized clinical manifestations, pericarditis, rheumatologic
      syndromes, esophageal compression, and sarcoid-like manifestations are well
      recognized complications of histoplasmosis. Although excellent laboratory methods
      for diagnosis are available, diagnosis in many cases is missed or delayed because
      histoplasmosis is not considered in the differential. Physicians must be aware of
      the clinical syndromes and take advantage of epidemiologic clues. Furthermore,
      clinicians must be familiar with the uses and limitations of a battery of
      serologic and mycologic tests. Cultures, fungal stains, antigen detection, and
      serologic tests for antibodies are useful for diagnosis of histoplasmosis. All
      are reasonably specific and can serve as the basis for diagnosis in patients with
      compatible clinical findings. Each has certain limitations that must be
      recognized if they are to be used correctly. The approach to diagnosis of
      histoplasmosis will be reviewed.

PMID- 11521246
TI  - Treatment of histoplasmosis.
AB  - Histoplasmosis is an endemic mycosis, which is most prevalent in the Ohio and
      Mississippi valleys of North America. The causative organism is a dimorphic
      fungus, Histoplasma capsulatum. Histoplasmosis can present as a self-limited
      disease or cause life-threatening diseases resulting in considerable morbidity
      and mortality. Treatment is appropriate in patients with diffuse acute pulmonary
      infection, chronic pulmonary infection, mediastinal granuloma causing obstruction
      of important structures, or disseminated infection. Other chronic forms of
      disease such as fibrosing mediastinitis and broncholithiasis are unresponsive to
      pharmacologic treatment. Options for therapy include amphotericin B or one of its
      lipid formulations, and ketoconazole, itraconazole, or fluconazole. Recently,
      newer antifungal agents have been evaluated in animals models of histoplasmosis.
      Of these, a new triazole, posaconazole (SCH56592) appears most promising.
      Generally, amphotericin B or one of the lipid formulations is recommended as
      initial treatment in patients with more extensive diseases, felt to be ill enough
      to require hospitalization, and itraconazole for those who have milder illness,
      or to complete treatment after patients respond to amphotericin B. The role of
      intravenous formulation of itraconazole for severe histoplasmosis is unknown
      because studies comparing it with amphotericin B have not been conducted.

PMID- 11521247
TI  - Diagnostic case study: miliary tuberculosis and Pott's disease.

PMID- 11521248
TI  - The year in review. A panoply of product approvals.

PMID- 11521249
TI  - Soy. Health claims for soy protein, questions about other components.

PMID- 11521250
TI  - Escaping the prison of a past trauma. New treatment for post-traumatic stress
      disorder.

PMID- 11521251
TI  - Arthritis. Timely treatments for an ageless disease.

PMID- 11521252
TI  - Cosmetic laser surgery. A high-tech weapon in the fight against aging skin.

PMID- 11521253
TI  - Manufacturing misdeeds cost Abbott record-breaking payment.

PMID- 11521254
TI  - FDA takes action to enforce the law.

PMID- 11521255
TI  - Long-distance house calls. Telemedicine moves into the house.

PMID- 11521256
TI  - Pharmaceuticals: conspiracy to increase ritalin profits alleged.

PMID- 11521257
TI  - EMTALA: duty extends to even non-transferring emergency patients.

PMID- 11521258
TI  - Research guidelines: changes urged.

PMID- 11521259
TI  - Insurance: exclusion of contraception found discriminatory by EEOC.

PMID- 11521260
TI  - Medical practice: HCFA's proposed final rule for Stark II provisions.

PMID- 11521261
TI  - Bioethics: court strikes down Arizona ban on fetal tissue experiments.

PMID- 11521262
TI  - Malpractice: ruling on state-agent immunity overturned in Alabama.

PMID- 11521263
TI  - Relieving unnecessary, treatable pain for the sake of human dignity.

PMID- 11521264
TI  - Evidence: admissibility of attorney's health record.

PMID- 11521265
TI  - Antitrust: hospitals may grant C-section privileges only to obstetricians.

PMID- 11521266
TI  - Malpractice: damages limited to amount that Medicare paid out.

PMID- 11521267
TI  - The girl who cried pain: a bias against women in the treatment of pain.

PMID- 11521268
TI  - Pain management and provider liability: no more excuses.

PMID- 11521269
TI  - Argument against ethicists' testimony logically flawed.

PMID- 11521271
TI  - Two courts rule against admissibility of testimony.

PMID- 11521270
TI  - Test of admissibility should be framed another way.

PMID- 11521272
TI  - Race, ethnicity, and pain treatment: striving to understand the causes and
      solutions to the disparities in pain treatment.

PMID- 11521273
TI  - From confrontation to collaboration: collegial accountability and the expanding
      role of pharmacists in the management of chronic pain.

PMID- 11521274
TI  - Federal training requirements for responsible research: not going far enough.

PMID- 11521275
TI  - [Effect of highly active antiretroviral therapy (HAART) on hypergammaglobulinemia
      in HIV infected patients].
AB  - To investigate the mechanism of hypergammaglobulinemia in HIV infected patients,
      the effect of highly active antiretroviral therapy (HAART) on the
      hypergammaglobulinemia was analyzed. Involved in this study were 34 untreated, 21
      HAART-effective (complete response) and 14 HAART-non-effective (partial response)
      patients. Serum levels of HIV-RNA and gammaglobulin and immunoglobulin (Ig)
      isotypes were measured. Mean HIV-RNA levels of untreated and partial response
      patients were 1.6 x 10(4) copies/ml and 0.4 x 10(4) copies/ml, respectively. HIV
      RNA levels of all complete response patients were below 4.0 x 10(2) copies/ml.
      Mean gammaglobulin percentages of untreated, partial response and complete
      response patients were 24.4%, 21.8% and 17.9%, respectively (p < 0.01 in
      untreated vs complete response patients). Mean IgG levels in the three groups
      were 2,489 mg/dl, 1,947 mg/dl and 1,618 mg/dl, respectively (p < 0.001 in
      untreated vs complete response patients). IgA levels were high in some untreated
      patients and lower in complete response patients. IgE levels were increased in
      some untreated and partial response patients, but there was no significant
      difference among the three groups. These results suggested that the
      hypergammaglobulinemia found in HIV infected patients was associated with HIV
      replication. The activation mechanism might differ by Ig isotypes.

PMID- 11521276
TI  - [Epidemiological study on vancomycin-resistant enterococci from fecal samples in
      the east area of Japan].
AB  - Recently, Vancomycin-resistant enterococci (VRE) have become important nosocomial
      pathogens in the world. In Japan, the VRE-infection was first reported in 1996.
      However, an epidemiological study on VRE has not been aggressively done in Japan.
      We conducted a survey study to explore the incidence and antimicrobial
      susceptibility of vancomycin-resistant enterococci isolated from fecal samples at
      45 hospitals in the east area of Japan (Kanto, Koshinetsu, Tohoku, and Hokkaido)
      during June 1998 to March 1999. The Enterococcosel agar containing vanocomycin
      (BBL) was used for screening VRE from fecal samples in each hospital. The
      susceptibilities of the isolates to 8 antimicrobials were determined by the broth
      microdilution method and the definitions of resistance were based on current
      standards of the NCCLS standards. The VRE genotypes (vanA, vanB, vanC1, and van
      C2/3) were confirmed by amplifying the respective genes by PCR. Eight hundred and
      ninety four strains of enterococci were tested by the microtiter plates
      hybridization method (WAKUNAGA SEIYAKU, Japan). One thousand five hundred eighty
      three strains of enterococci were collected from 6,914 patients in 45 hospitals.
      These strains included 72 (4.5%) strains Enterococcus faecalis, 33 (2.1%) strains
      Enterococcus faecium, 17 (1.1%) strains Enterococcus avium, 1,040 (65.7%) strains
      Enterococcus gallinarum, 386 (24.4%) strains Enterococcus cassliflavus, and 35
      (2.2%) strains Enterococcus flavescens. These strains of vancomycin-resistant E.
      faecalis were isolated from 3 patients, two of these 3 strains had van A gene and
      other one had van B gene. Those 3 strains were in the Kanto area, and 2 of 3
      strains were in Tokyo, Generally, though van A type VRE was highly resistaant to
      both vancomycin and teicoplanin. In our study, two strains of van A type E.
      faecalis were highly resistant to vancomycin (MICs > 128 micrograms/ml) and
      susceptible to teicoplanin with MICs 4 micrograms/ml. Those two strains were
      different in susceptibilities of minocycline and ofloxacin. The result of the
      analysis of PFGE had also different patterns. VanB type E. fecalis was highly
      resistant to vancomycin and susceptible to teicoplanin (MICs 0.25 microgram/ml).
      For ampicillin and imipenem, 3 strains of E. faecalis were susceptible (MIC < or
      = 1 microgram/ml). One of 562 strains of E. gallinarum had vanB and vanC1 genes
      and was moderately resistant to vancomycin and susceptible to teicoplanin. All
      strains of E. casseliflavus and E. flavescens had vanC2/C3 gene only. All strains
      of E. faecium and E. avium did not detect van genes. From this result, it was
      supposed that VRE were very rare in the east of Japan.

PMID- 11521277
TI  - [Drug susceptibility of clinically isolated strains of Neisseria gonorrhoeae].
AB  - We investigated the drug susceptibilities of Neisseria gonorrhoeae by using 98
      strains of clinical isolates at Toho University Omori Hospital from 1994 to 1998.
      Minimum Inhibitory Concentrations (MICs) of 15 antimicrobial agents were
      determined with agar dilution methods according to the guidelines of NCCLS. Among
      these isolates, only 4 strains (4.1%) were found to be penicillinase producing N.
      gonorrhoeae. Ceftriaxone showed the most potent activity of which MICs of all
      strains were 0.06 microgram/ml or less. Macroride antimicrobial agents and
      minocycline also showed strong activities of which MICs of most of the strains
      were 0.06 microgram/ml or less. With the criteria of NCCLS, 10 strains (10.2%)
      were found to be resistant to ciprofloxacin and these 10 strains also showed
      cross resistance to other fluoroquiolones we tested. Our results also revealed
      that the number of resistant strains against fluoroquiolones abruptly increased
      from 1996 and indicate the needs of further surveillance of antimicrobial
      resistance in clinical isolates of N. gonorrhoeae.

PMID- 11521278
TI  - [Longitudinal study of serological response to Bartonella henselae by indirect
      fluorescence assay in cat scratch disease].
AB  - Sequential serologic testing for IgG and IgM titers to Bartonella henselae were
      evaluated by an indirect fluorescence assay (IFA) in patients with CSD. The IFA
      test for the detection of IgG and IgM antibodies to B. henselae in 52 CSD
      patients showed that 40 (76.9%) were positive for IgG antibody and 9 (17.3%) were
      positive for IgM antibody. Two or more consecutive serum samples from 30 patients
      with CSD were assessed. In regard to the detection of IgG antibody, 5 patients
      had rapidly elevated titers in the acute phase, 12 patients had high titers from
      the acute phase, and 5 patients had a positive titer 24 weeks after the onset. B.
      henselae IgM antibody kinetics varied widely between patients with CSD. The
      seropositive rate for the antibody to B. henselae was analyzed at overtime after
      the onset and we found that the IgG-seropositive rate was high from 2 weeks after
      the onset and low after 25 weeks. The sensitivity of the IgM IFA was low, and IgM
      antibody to B. henslelae was not detected from 9 weeks. The detection from
      consecutive serum samples of antibodies to B. henselae by IFA is very useful for
      diagnosis in the case of clinically suspected CSD.

PMID- 11521279
TI  - [Demonstration of Chlamydophila pneumoniae and Chlamydia stress protein, HSP-60
      in heart muscle tissue].
AB  - There has been much attention to the association between Chlamydophila pneumoniae
      and athrosclerosis since C. pneumoniae was demonstrated in macropharges, and
      vascular smooth muscle cells of atheroma tissues. There are few data
      demonstrating whether C. pneumoniae is present in other tissues than
      atherosclerotic tissues. We surveyed samples of heart tissue from 10 patients
      with ischemic heart disease and 10 patients with other disease by
      immunohistochemical staining with monoclonal antibodies against C. pneumoniae and
      Chlamydia stress protein 60 (C. HSP-60). In all, 11 out of 20 (55.0%) samples
      were positive for C. pneumoniae and 7 out of 20 (35.0%) for Chlamydia HSP-60. In
      patients with ischemic heart disease, positive rates were found significantly
      higher, that is, 9 out of 10 (90.0%) were positive for C. pneumoniae and 6 out of
      10 (60.0%) for Chlamydia HSP-60. These results indicate the common presence of C.
      pneumoniae in heart tissue in older patients with ischemic heart diseases.

PMID- 11521280
TI  - [A case of rhabdomyolysis associated with influenza A viral infection given an
      useful early diagnosis by Tc-99m bone agent scintigraphy].
AB  - Rhabdomyolysis is a syndrome resulting from skeletal muscle injury with release
      of muscle cell contents into the plasma. It is often associated with alcohol
      abuse, muscle compression and generalized seizure. It may also follow viral
      infections like influenza. Tecnetium-99m phosphate compounds are useful for bone
      scintigraphy. But proper interpretation of this bone agent scintigrams must
      include careful analysis of extraskeletal accumulations, such as cerebrospinal
      lesions, carcinoma, acute myocardial infarction, myocarditis and inflammatory
      myopathy. This case was a 74-year-old female who developed rhabdomyolysis
      associated with influenza A viral infection. We report the usefulness of
      Tecnetium-99m phosphate scintigraphy for early diagnosis, location and extent of
      the muscle damage of viral induced rhabdomyolysis.

PMID- 11521281
TI  - [Evaluation of m-TM agar, a new selective medium, for isolation of Neisseria
      gonorrhoeae from a pharynx specimen].

PMID- 11521282
TI  - [Incidence of amantadine-resistant influenza A virus isolated in 1999/2000.
      Epidemic season in Shizuoka Prefecture].

PMID- 11521283
TI  - [FGFs as multifunctional signaling molecules: diversity of structure and
      function].

PMID- 11521284
TI  - [Novel insights on the structure and function of ABC transporters].

PMID- 11521285
TI  - [Whole genome sequence of MRSA (methicillin-resistant Staphylococcus aureus)-
      pathogenesity is carried by mobile elements].

PMID- 11521286
TI  - [Reactive oxygen species and G proteins].

PMID- 11521287
TI  - [Molecular design of functional peptides which contain unnatural components:
      toward novel intracellular probes].

PMID- 11521288
TI  - [Cross talk between activation of phospholipase D and phospholipid signaling].

PMID- 11521289
TI  - [Regulation of protein phosphatase 1 by endogenous inhibitors: identification of
      I-4].

PMID- 11521290
TI  - [Regulation of the cytoskeletons by heterotrimeric G proteins through Rho family
      small G proteins].

PMID- 11521291
TI  - [The probability of impaired health in workers exposed to occupational hazards].
AB  - Complex descriptive, physiologic and hygienic studies covered various
      occupational groups of physical and mental work and revealed that health
      disorders probability depends on intensity of occupational factors. Increase in
      the intensity results in higher physiologic expenditure and greater incidence of
      occupational diseases. Symptoms of disorders appeared to depend on specificity of
      occupational factors.

PMID- 11521292
TI  - [The role of inhalation provocation tests in the diagnosis of occupational
      bronchial asthma].
AB  - Light industry female workers suffering from bronchial asthma demonstrated
      significant pulmonary ventilation disorders of mixed type with prevalent
      bronchial obstruction. Those changes prove long-standing harm caused by
      occupational factors. Inhalation provocative tests point out leading role of
      industrial dust in increased bronchial reactivity.

PMID- 11521293
TI  - [The status of the vegetative nervous system in vibration disease patients].
AB  - Vibration disease patients demonstrate severe vegetative disorders of peripheral
      and supersegmental levels of nervous system, also involved cerebral and
      cardiovascular structures, and minimal changes in respiratory and digestive
      systems. Findings are early signs of generalized vegetative disorders showing
      neurovascular changes both in upper and lower limbs. All vegetative disorders
      revealed are progressing.

PMID- 11521294
TI  - [Influence of low-frequency magnetotherapy and HF-puncture on the heart rhythm in
      hypertensive workers exposed to vibration].
AB  - The authors present results concerning use of low-frequency magnetic fields and
      HF-therapy for correction of vegetative homeostasis in workers with variable
      length of service, exposed to vibration, having early forms of arterial
      hypertension. The most positive changes of vegetative status and central
      hemodynamics are seen in workers with low length of service.

PMID- 11521295
TI  - [Methods to map traffic noise in cities].
AB  - The authors suggest a method evaluating acoustic situation on traffic pathways
      with restricted volume of direct measurements. The regression equations obtained
      could forecast equivalent noise levels changing with city growth and with shifts
      of traffic flow between routes.

PMID- 11521296
TI  - [Physiological-occupational requirements with reference to clothes protecting
      workers from low temperature and methods for the evaluation of heat insulation].
AB  - The authors specified a method regulating clothes production in accordance with
      physiologic and hygienic requirements that result from particular utilization
      conditions (ambient temperature, motion speed, energy expenditure, duration of
      exposure to cold). The article represents criteria for allowable heat state of
      human, requirements to heat insulation of clothes set and items (hat, mittens,
      and shoes) for various climate areas, for allowable duration of exposure to cold.

PMID- 11521297
TI  - [Occupational morbidity among workers of the Magnitogorsk metallurgic plant].

PMID- 11521298
TI  - [Influence of noise and infrasound on the vision organs].

PMID- 11521299
TI  - [Biological age and thermoregulation in female workers of the shoe production
      factory].

PMID- 11521300
TI  - [Clinico-immunological basis for the classification of occupational bronchial
      asthma].
AB  - The authors tackle problem of occupational bronchial asthma classification. The
      article deals with up-to-date diagnostic methods providing new materials on
      occupational bronchial asthma pathogenesis. Those methods justified definition of
      specific forms of occupational bronchial asthma. The authors defined:
      occupational bronchial asthma allergic, non-allergic, mixed.

PMID- 11521301
TI  - [Choice of the method of treatment of uncomplicated gastric and duodenal ulcers].
AB  - Three features of ulcer prevalence in Russia and therapeutic policy in ulcer
      consist of an increase of ulcerous patients number, a decrease of elective
      operations number for uncomplicated ulcers and an increase of emergency
      operations rate in complicate ulcer. Decrease of elective operations number leads
      to increase of emergency operations rate in complicated ulcer. The majority of
      complicated ulcers has long-term anamnesis, complications develop in chronic
      ulcers. Expansion of indications to elective operations in uncomplicated gastric
      and duodenal ulcer is advocated.

PMID- 11521302
TI  - [Use of present-day suturing instruments in gastrointestinal surgery].
AB  - Since 1993, 272 patients underwent surgery on gastrointestinal tract: 92--for
      gastric ulcer, 79--for duodenal ulcer, 29--for cancer of the stomach, 67--for
      cancer of the colon, 5--for other diseases. The main operations were resection of
      the stomach (195), hemicolectomy (23), abdominal-anal and anterior resection of
      the rectum (44). In 135 patients group 1 all stages of surgery on
      gastrointestinal tract were performed with "Auto Suture" instruments (USA). In
      137 patients group 2 anastomosis was created by two-layer nodal suture with
      Russian auto-suture instruments (UKL-60, UO-40) during some stages of operation.
      Postoperative complications occurred in 57 (20.9%) patients: 14 (5.1%) in group 1
      and 43 (15.8%) in group 2. Predominant complications were suppuration of the
      wound (7 and 14 cases, respectively), anastomositis (2 and 10), pneumonia (8-
      only in group 2), bleeding in anastomotic zone (5--only in group 2). After
      surgery 7 (2.6%) patients died due to causes not associated with method of
      surgery or anastomosis creation. Advantages of modern auto-suture instruments in
      surgery of gastrointestinal tract are demonstrated: reduction of surgery time,
      simplicity and reliability of anastomosis creation, possibility of use in hard to
      reach abdominal parts (low anterior resection of the rectum), better
      postoperative period, a 3-fold decrease of postoperative complications number.

PMID- 11521303
TI  - [Immune and enzyme disorders in patients with acute pancreatitis].
AB  - Analysis of immune and enzyme disorders in 85 patients with acute pancreatitis
      shows that persistent imbalance of immunoregulatory T-lymphocytes with
      suppression predominance; reduction of all immunoglobulines number, imbalance in
      phagocytic immunity with height of absorbing activity of neutropils and
      stimultaneous decrease of their digestive capacity are prognostically
      unfavourable for high risk of pyonecrotic complications and lethal outcome.  It
      is necessary to include immunocorrectors in combined therapy.  Direct assessment
      of leukocytic elastase activity and alpha-IP level in blood plasma permits to
      evaluate spreading of inflammatory process and it severity, efficacy and
      prognosis of treatment.

PMID- 11521304
TI  - [Diagnosis and treatment of acute adhesive small intestine obstruction].
AB  - Experience of treatment of 162 patients with acute adhesive intestinal
      obstruction (AAIO) is described. These patients had most often (23.3%)
      appendectomy in anamnesis. Conservative treatment was effective in 23 (14.2%)
      patients only. Surgical treatment was performed in 139 (85.8%) patients including
      traditional open operation in 79 (56.8%) patients, laparoscopic and laparoscopy
      assisted in 60 (43.2%). Advanced adhesive process with formation of single
      intestinal conglomerate, neglected forms of AAIO with paralytic ileus were
      indications to open operations; lethality in these operations was 17.7%.
      Laparoscopic operation was indicated in AAIO due to isolated commissure as well
      as in early adhesive obstruction; lethality was 1.7%. If diagnostic laparoscopy
      showed that AAIO is caused by intestinal deformation in small intestinal
      conglomerate or intestinal resection is required, laparoscopy-assisted operations
      were performed.

PMID- 11521305
TI  - [Treatment of villous adenoma of distal parts of the colon].
AB  - Results of treatment of 78 patients (mean age 64 years) operated for benign
      neoplasms of a colon distal part are presented. In histologic examination tubular
      adenoma was found in 34 cases, tubular-villose adenoma--in 27, villose adenoma
      with different degree of epithelium dysplasia--in 16. In 10 patients villous
      tumors were located in low-ampular part of the rectum at the distance less than 7
      cm from dermal-mucose line of the anal canal, in 27 patients--at 8 to 12 cm, in
      42--at 12 to 20 cm. Area of neoplasm base in 53 patients ranged from 1.0 to 2.0
      cm2, in 15--from 2.1 to 6 cm2, in 11-43 cm2, it was 14 cm2 on the average. For
      patients of the first group wire endoscopic polipectomy was adequate procedure.
      In 25% patients with neoplasm area more 2 cm2 recurrence of the disease was
      revealed from 3 months to 1 year after staged endoscopic polipectomy. Possibility
      of incomplete removal of creeping neoplasm at staged endoscopic electroexcision
      dictates the necessity of control colonoscopy 1 month after the procedure. If
      villous tumor recurs during 1 year in spite of repeated endoscopic procedures, it
      is reasonable to resect the colon because of danger of malignant transformation
      of the tumor. In 12 patients with villous adenomas location at 7-20 cm from the
      anal ring transanal endoscopic microsurgery (TEM) by G. Buess et al (1984) was
      performed. In follow-up for 25.8 months on the average recurrences of the disease
      were not revealed. TEM is thought as alternative to anterior resection of the
      rectum in benign tumors.

PMID- 11521306
TI  - [Principles of the treatment of surgical diseases in elderly and aged patients
      with diabetes mellitus].
AB  - Based on his experience of treatment of more than 5000 diabetic patients with
      surgical diseases, the author describes basic principles of management of these
      patients before, during and after operation. Combined treatment is based on
      compensation of diabetes, fluid-and-electrolyte balance and acid-base
      equilibrium. Blood glucose before operation must be limited to 8.3-8.7 mmol/l,
      ketoacidosis must be absent. During 3-4 days after operation doses of insulin
      must increase from 0.4-0.5 to 0.8-0.9 U/kg. Energy value of the diet must be not
      less than 9375-10,450 kJ bearing in mind glucose administered intravenously.
      Choice of the anesthetic method which has the least negative influence on
      carbohydrate metabolism and hemostasis as a whole is analyzed. Diabetic patients
      with surgical diseases can be operated with favourable outcome only in
      compensated diabetes and balanced homeostasis.

PMID- 11521307
TI  - [Correction of hyperglycemia in diabetic patients with postinjection abscesses].
AB  - Local use of oxytocin-antibacterial complexes in combination with treatment of
      diabetes including divided insulinotherapy in patients with postinjection
      abscesses and non-insulin-dependent diabetes led to compensation of diabetes and
      earlier sanation of suppurative focus compared with patients treated by local
      antibiotics only.

PMID- 11521308
TI  - [Surgical treatment of aneurysms of unpaired visceral branches of the abdominal
      aorta].
AB  - Aneurysms of unpaired visceral branches of the abdominal aorta are rare diseases
      but they are dangerous for life. Russian Research Center of Surgery RAMS has an
      experience of diagnosis and surgical treatment of 23 patients with aneurysms of
      the celiac trunk (2), superior mesenteric artery (4), inferior mesenteric artery
      (1), hepatic artery (4), splenic artery (7), gastroduodenal artery (2), inferior
      pancreatoduodenal artery (1), multiple aneurysms of celiac trunk and superior
      mesenteric artery (2). 21 of 23 patients were operated. 20 patients were
      discharged with complete recovery. 1 (4.8%) patient died due to gastroduodenal
      bleeding 4 months after surgery. The results show that patients with aneurysms of
      unpaired visceral branches of abdominal aorta require surgical treatment.

PMID- 11521309
TI  - [Features of surgical infection of soft tissues].
AB  - Microflora from surgical infection foci of soft tissues was studied in 92
      patients with local, 78 patients with spread and 10 patients with generalized
      forms of pyo-inflammatory processes. Increase of bacterial contamination of
      surgical infection foci, more frequent detection of gram-negative bacteria,
      associations of microorganisms, high antibiotics resistance and persistent
      characteristics of bacteria in spread and generalized forms of surgical
      infections were found. Increase of persistent potential of infective agents is
      significant for prolongation of the disease and generalization of infectious
      process.

PMID- 11521310
TI  - [Experience in clinical use of quamatel in upper gastrointestinal hemorrhage].

PMID- 11521311
TI  - [Endoscopic method of the treatment of acute suppurative lung abscesses].

PMID- 11521312
TI  - [Endoscopic papillosphincterotomy in papillary diverticula].

PMID- 11521313
TI  - [Surgical methods of the treatment of sequelae of trunk burns].

PMID- 11521314
TI  - [Academician B. V. Petrovskii -- Head of Hospital Surgical Clinic].

PMID- 11521315
TI  - [X-ray computed tomography in the diagnosis of mediastinitis].
AB  - Results of X-ray computed tomography (RCT) use in 21 patients treated for acute
      mediastinitis in N.V. Sklifosovsky Emergency Care Research Institute have been
      analyzed retrospectively. RCT proved able to defect accurate location, spreading
      and sizes of inflammatory disorders in the mediastinum are demonstrated.
      Semiotics of mediastinitis depending on location, spreading and phase of
      inflammatory process is presented.

PMID- 11521316
TI  - The shrinking pool of plans.

PMID- 11521317
TI  - When it comes to health care, employees want it all.

PMID- 11521318
TI  - Drugmakers exit the comfort zone.

PMID- 11521319
TI  - Managed care in the courtroom.

PMID- 11521320
TI  - Defined contribution, the undefined concept.
AB  - A new method for financing employee health benefits is said by many to be the
      hope of the future, but lack of understanding and a heavy dose of employer
      paternalism have kept the discussion theoretical.

PMID- 11521321
TI  - The view from Washington.

PMID- 11521322
TI  - The states' solutions.
AB  - Tired of waiting for Washington to act, governors and legislators are becoming
      reluctant reformers. A heady mix of proposals is seasoned by money problems and
      well stirred by neophyte legislators.

PMID- 11521323
TI  - It's a hard knocks life for providers ... and getting harder!

PMID- 11521324
TI  - The quality thing.

PMID- 11521325
TI  - Paper, paper everywhere.

PMID- 11521326
TI  - Getting down to the numbers. Can the value of health care really be quantified?

PMID- 11521327
TI  - Viewpoint: private employers and public health. Interview by Rick Service and
      Annmarie Geddes Lipold.

PMID- 11521328
TI  - A look into the crystal ball.

PMID- 11521329
TI  - A relapse of inflation.

PMID- 11521330
TI  - [No growth hormone to intensive care patients. Doubled mortality in an extensive
      multicenter study].

PMID- 11521331
TI  - [Gender perspective can result in better research on sex differences and
      revascularization].
AB  - This article focuses on how sex differences in revascularization, PTCA and CABG,
      are discussed in medical research. We selected and analyzed 10 articles
      identified through Medline, for the purpose of studying such discussions. Three
      explanatory models were identified by qualitative analysis: biological,
      psychosocial and discriminatory. Although the articles focused on sex differences
      in revascularization, the discussions in the articles on this issue were sparse.
      We demonstrate how a gender perspective can generate new questions and theories
      and contribute to a better prognosis for women and men with heart disease.

PMID- 11521332
TI  - [Management of cardiovascular diseases is characterized by male perspective.
      Women are subjected to incorrect management, diagnosis and treatment].
AB  - In women as well as in men cardiovascular disease is common, and almost as many
      women as men suffer from myocardial infarction every year in Sweden. In spite of
      this, studies on female cardiovascular disease are few in number. Knowledge about
      differences in risk factors, prevention, treatment and management is not common.
      Female cardiovascular disease starts approximately ten years later than in men
      and consequently most women are excluded from studies because of low age limits
      for inclusion. Primary preventive effects of e.g. acetylsalicylic acid, lipid
      lowering drugs, vitamins and exercise have only been studied in healthy men, but
      the conclusions have been applied on women as well. The effects of reducing
      triglyceride levels or abdominal obesity in women--important risk factors for
      cardiovascular disease--have not been studied in controlled randomized studies.
      In women, angina is a non-specific symptom, and false positive ECG's are much
      more frequent than in men. The fact that a woman has to present as a man in order
      to be treated professionally (the Yentl syndrome) is still at hand. There is a
      great need for spreading current knowledge regarding gender differences among
      colleagues and medical students.

PMID- 11521333
TI  - [Electrical conversion of atrial fibrillation. Superior effects of biphasic
      transthoracic method when compared with the conventional monophasic method].
AB  - Can biphasic electrical conversion of atrial fibrillation replace the standard
      monophasic method? This report reviews factors facilitating the electrical
      conversion of atrial fibrillation and describes a clinical trial, showing
      superior effects of biphasic versus monophasic electrical conversion of atrial
      fibrillation. We conclude that the most important factors for successful
      electrical conversion of atrial fibrillations are 1) a biphasic impulse, 2) low
      transthoracic impedance and 3) a short history of atrial fibrillation.

PMID- 11521334
TI  - [Done is done--and gone is gone. Sex reassignment is presently the best cure for
      transsexuals].
AB  - Sweden was the first country to legislate on sex reassignment procedures in 1972.
      Patients with gender dysphoria are in Sweden referred to one of six university
      clinics specialised in the field; all surgery, however, is centralised to the
      Karolinska Hospital in Stockholm. The aetiological strivings regarding
      transsexualism have to date been inconclusive; however, several lines of evidence
      speak in favour of an early biological influence on gender identity. The vast
      majority of studies addressing outcome have provided convincing evidence for the
      benefit of sex reassignment surgery in carefully selected cases. The current
      article summarises the state of the art regarding work-up and treatment of
      transsexuals.

PMID- 11521335
TI  - [Dientamoeba fragilis--an old parasite sparks new interest].
AB  - Dientamoeba fragilis is a protozoan parasite of the human colon with only the
      trophozoite stage identified. The exact mode of transmission is still unknown.
      Formerly considered to be apathogenic, several studies have suggested that D.
      fragilis has pathogenic properties. Common symptoms of the infection include
      diarrhea and abdominal pain. After reviewing the literature we suggest that
      treatment can be considered for patients with prolonged symptoms, provided no
      other causative agent has been found.

PMID- 11521336
TI  - [Botryomycosis--peculiar bacterial granuloma].
AB  - Botryomycosis is a chronic granulomatous infection, usually of skin or mucous
      membranes in predisposed individuals. Infection in internal organs may occur in
      immunosuppressed persons and is serious but uncommon. Trauma or foreign bodies
      and defective immune defense mechanisms predispose for the disease, which is
      mainly caused by Staphylococcus aureus, but also by other bacteria. The
      histopathological picture is diagnostic and biopsy is encouraged in granulomatous
      infections. Differential diagnoses may be mycobacteriosis, mycosis and
      parasitosis. If excision, the preferred treatment, is not radical, prolonged
      antibiotic treatment is required. The disease may become more widespread in
      connection with the common use of piercing in young immunocompetent persons.

PMID- 11521337
TI  - [Ethylene glycol and methanol poisoning. Fomepizole--an alternative antidote].

PMID- 11521338
TI  - [Inventory of internal medicine in Sweden. Medical safety is endangered by
      massive turnover per occupied bed].

PMID- 11521339
TI  - [NEPI evaluated by Danish and Norwegian experts].

PMID- 11521340
TI  - [A little prefix means so much--paradoxically].

PMID- 11521342
TI  - [General practice should be given it's rightful place within health care!].

PMID- 11521341
TI  - [Wilhelm Wernsted proved the origin of the immunity against polio. A stubborn
      fight against child paralysis].

PMID- 11521343
TI  - [Sick leave--rehabilitation--pension. A quality problem?].

PMID- 11521344
TI  - [The WMA must take action against capital punishment].

PMID- 11521345
TI  - [Surgery of excessive hand sweating in the past and now].

PMID- 11521346
TI  - [Draco's recall of certain anti-asthmatic agents makes children's treatment more
      expensive].

PMID- 11521348
TI  - [Training is required for users of a screening tests].

PMID- 11521347
TI  - [Let the methadone patients in Stockholm tell--with the possibility to change
      their program].

PMID- 11521349
TI  - [To compare male circumcision with Jehovah's Witnesses' refusal of blood
      transfusion is not relevant].

PMID- 11521350
TI  - [Thanks for better referrals of obese patients!].

PMID- 11521351
TI  - [Report on th SPUR-inspection of 2001. Specialist training in cardiology--better
      but can be further developed].

PMID- 11521352
TI  - The use of metronidazole in the treatment of periodontal diseases.
AB  - Diagnostic microbiology and the use of antibiotics should be considered as
      available tools in periodontal therapy. It appears that the dental health
      profession has yet to develop a consensus as to whether or not the use of
      antibiotics alone can wholly or partially replace traditional treatments such as
      debridement and surgery. The combined use of periodontal microbiology and
      antibiotic therapy, however, perhaps qualifies as an extension of traditional
      courses of treatment following a proper clinical diagnosis. Metronidazole offers
      the periodontist (therapist) the benefits of a high degree of efficacy and
      relatively few and/or mild adverse side effects. Also it is an antibiotic to
      which susceptible anaerobes have yet to develop clinical resistance. Therefore,
      it qualifies as the preferred drug against anaerobic infections under this
      combined treatment program.

PMID- 11521353
TI  - Bush draws a stem cell line.

PMID- 11521354
TI  - Overexposed.
AB  - Skin cancer: with temps rising, so are rates of this deadly. How scientists are
      hunting for new treatments--and better approaches to prevention.

PMID- 11521355
TI  - My life has been full of narrow escapes. John McCain and his wife, Cindy, on the
      senator's battle with melanoma.

PMID- 11521356
TI  - Valuing the donor more than the donation.
AB  - The "valuing the donor more than the donation" approach is based on a respect for
      each individual donor and their needs. In order for the long-term value of the
      donor/charity partnership to be realized, there must first be an appreciation of
      the need for a carefully cultivated relationship.

PMID- 11521357
TI  - The coordinated development approach.
AB  - A development office desires to emphasize major and planned gifts in order to
      build the results of its fund raising. Many institutions now have separated the
      three programs of giving and operate each as a separate entity. While there are
      certain unique steps that need to be taken for each program, the linkage and even
      overlap of these sources of revenue need to be crafted into a development
      operation.

PMID- 11521358
TI  - Everybody loves a party.
AB  - You should have some clear goals in mind before you start a special event. Early
      on, take the time to think things through carefully before giving any event a
      green light. You will be glad that you invested the time.

PMID- 11521359
TI  - Cutting through the e-maze: marketing strategy (Part II).

PMID- 11521360
TI  - Securing the major gift: persistence, respect and timing.
AB  - I have often said when a request has been made, "It has to be right for the
      donor." These two stories bear that out. A guiding principle for development
      officers should be: practice respect, be cognizant of timing, and keep at it ...
      be persistent.

PMID- 11521361
TI  - How to quote your way to better copy.

PMID- 11521362
TI  - Volunteerism under the magnifying glass.
AB  - Are you making a concerted effort to seek out and attract those volunteers who
      can really add value to your cause? Do you place as much emphasis on recruiting
      volunteers for the long-term as you do when hiring employees? Arguably, the
      answers to all of these questions should be a resounding "yes."

PMID- 11521363
TI  - A skin cancer primer for primary care.

PMID- 11521364
TI  - Pediatric exanthems: recognize the rash.

PMID- 11521365
TI  - The clinical challenge of onychomycosis.
AB  - Onychomycosis continues to be a difficult diagnosis to establish and treat.
      Better testing modalities need to be developed. Although new antimycotic agents
      [table: see text] are far more promising than previous treatments, relapse rates
      remain high. Patient education must be a mainstay of therapy. Establishing
      realistic expectations, providing a detailed treatment plan with follow-up, and
      reviewing preventive measures will enhance patient satisfaction and improve cure
      rates.

PMID- 11521366
TI  - The diagnostic value of a KOH.

PMID- 11521367
TI  - Scabies mites and lice. Identify and eradicate the unwelcome guest.

PMID- 11521368
TI  - Which technique to biopsy or remove a skin lesion?

PMID- 11521369
TI  - PAs and dermatology. Good times, nice work, and a special issue.

PMID- 11521370
TI  - Why taper prednisone in dermatology?

PMID- 11521371
TI  - [Risk factors and prevention of strokes].

PMID- 11521372
TI  - [Altered left ventricular diastolic function in patients with
      lymphogranulomatosis].
AB  - Impaired elastic characteristics of the left heart ventricle and restructuring of
      its diastolic bloodflow were revealed in 28 patients with Hodgkin's disease by
      complex Doppler echocardiographic study of intracardiac hemodynamics. The most
      pronounced disorders of the diastolic function were detected in patients with
      pericardial involvement. More pronounced tumor intoxication in patients with
      mixed-cell variant of the tumor resulted in remodeling of the left ventricle,
      left atrial dysfunction, and restructuring of the diastolic bloodflow, which
      indicated combined impairment of the left ventricular diastolic relaxation and
      left atrial contractility. Chemotherapy augmented disorders in diastolic
      bloodflow, the increase in the number of polychemotherapy courses being
      associated with a trend to deterioration of left-ventricular relaxation. Hence,
      tumor intoxication and drug cardiotoxicity determine the formation of central
      hemodynamic disorders, one of whose principal components is diastolic dysfunction
      of the left heart ventricle.

PMID- 11521373
TI  - [The role of quantitative determination of the volume fraction of interstitial
      collagen and fibronectin in the pathogenesis of myocardial remodeling in dilated
      cardiomyopathy].
AB  - The role of myocardial fibrosis in the pathogenesis of left-ventriclar remodeling
      was studied in patients with idiopathic and ischemic dilatation cardiomyopathy. 
      The percentage of volumic collagen fraction in the left-ventricular myocardium
      was significantly increased, this increase correlating with the degree of
      dilatation of  left-ventricular cavity.  A sufficient increase of plasma
      fibromectin level was observed in patients with idiopathic dilatation
      cardiomyopathy at all stages of circulatory insufficiency.

PMID- 11521374
TI  - [The assessment of adaptation potential of circulatory system in non
      coronarogenic myocardial disease].
AB  - Adaptive potential of the circulatory system was estimated in 223 patients with
      non-coronary myocardial lesions (80 patients had spinal osteochondrosis with
      cardialgia, 78 patients were obese and 65 patients had neurocirculatory asthenia
      of the cardial type) in tests with submaximal exercise. 21 healthy subjects
      served control. It was found that submaximal exercise in rehabilitation does not
      change the adaptive potential in healthy subjects, lowers this potential in
      patients with neurocirculatory asthenia and raises in obese patients.

PMID- 11521375
TI  - [On changes in the cardiovascular system of patients with respiratory syncytial
      infection].
AB  - Cardiovascular status was evaluated in 36 adult patients with respiratory
      syncytial infection, part of these coronary patients and the other part not.
      Respiratory syncytial infection had a negative impact on the cardiovascular
      system, particularly so in coronary patients, exacerbating the course of coronary
      disease and causing focal changes in the myocardium.

PMID- 11521376
TI  - [Chronic gastroduodenal erosions: clinical and pathogenetic characteristics,
      classification, differential treatment].
AB  - The etiology of chronic (complete) gastroduodenal erosions is not quite clear and
      is apparently multifactorial. A total of 100 patients with chronic gastroduodenal
      erosions were examined and divided into 5 representative groups, 20 pts each. For
      objective evaluation of the significance of various (probable) etiological and
      pathogenetic factors in development of chronic erosions, monotherapies with drugs
      with known pharmacodynamic effects were used (ranitidine, double and triple
      antihelicobacter protocols, dalargin, trental). Triple antihelicobacter protocol
      and trental proved to be the most effective in the treatment of chronic erosions
      (90 and 85%, respectively). Dalargin and double antihelicobacter protocol caused
      disappearance of complete erosions in 50% patients and ranitidine in only 15%.
      Analysis of the frequency of erosion epithelialization and Helicobacter pylori
      eradication under the effect of antibiotics showed a clear-cut positive
      correlation (r = 0.9) between these parameters, which indicated an important role
      of Helicobacter pylori in the pathogenesis of chronic gastroduodenal erosions.
      Moderate antihelicobacter activity of dalargin was revealed for the first time.
      The results of this study indicate that the majority of complete erosions are an
      individual nosological entity. Microcirculatory disorders in the antral part of
      the gastric mucosa and its contamination with Helicobacter pylori play an
      important role in the disease development; decreased cytoprotection and local
      immunity in the antral part of the stomach are also. The acidopeptic factor
      cannot cause complete erosions but is one of conditions for their formation.

PMID- 11521377
TI  - [Microcirculation in patients with viral hepatitis B taking ephedrone].
AB  - Circulation in ocular conjunctival vessels was studied in patients with viral
      hepatites B and B + C. Intravascular, vascular (mainly venular), and capillary
      changes were observed during the acute period of disease. The most common
      disorders were erythrocyte aggregation, venous congestion, and reduction of
      capillary network. Use of narcotics augments the disorders in blood delivery.
      Pathological changes in microcirculatory system did not normalize by the end of
      hospital stay.

PMID- 11521378
TI  - [Melatonin and cardiovascular performance regulation].

PMID- 11521379
TI  - [The effectiveness of 7-day combined Helicobacter eradication therapy in patients
      with peptic ulcer and chronic gastritis].
AB  - Epidemiological and clinical findings suggest that the spread of Helicobacter
      pylori (H.p.) infection as an etiological and pathogenetic agent is of prime
      importance for patients with pelvic ulcer and chronic gastritis. However, there
      are relatively scanty papers on the impact of therapy against H.p. on its
      eradication rate, symptom arrest, and the course of diseases. A great deal of
      drug combinations have been proposed to eradicate H.p. infection and some of them
      are even classical (omeprazole in combination with 2-3 antibiotics). The H.p.
      eradication with this combination for 7 days is as high as 85-90%. These regimens
      are recommended for practical application in Europe and Russia. The authors'
      studies in 90 patients (34 with duodenal ulcers, 34 with gastric ulcers, and 28
      with chronic duodenitis) indicate that lansofed used in 7-day combined therapy is
      highly effective in suppressing acid production, abolishing symptoms during an
      exacerbation of peptic ulcer (gastroduodenitis) and in eradicating H.p.
      infection. There is evidence for that the use of the agent in combination with 2
      and 3 anti-H.p. drugs rapidly arrest the symptoms of a disease, frequently
      diminishes an inflammatory process and lead to a remission.

PMID- 11521380
TI  - [Life quality, mental status and specific features of the course of diseases in
      patients with peptic ulcer].
AB  - At present, medicine pays a great attention to studies into life quality (LQ) in
      patients. A relationship is examined between LQ and the course of a disease and
      the personality traits of a patient. Sixty patients with peptic ulcer (PU) were
      included in this study. The questionnaires filled by the patients were used to
      assess their LQ and the factors that modify LQ to the greatest degree, as well as
      personality traits and pain perception in patients. The same aspect of the
      patients' life was additionally evaluated by physicians. Studies indicated that
      LQ in patients was regularly decreased with their worse health. At the same time,
      there were increases in the degree of emotional stress and in the proportion of
      patients with depressive-hypochondriac personality traits and higher pain
      perception. At the same time the patients' emotional experiences and
      neurotization rather than the course of a disease were found to predominantly
      affect LQ. This is likely to be borne in mind in managing such patients.

PMID- 11521381
TI  - [Poseidonol in the treatment of hyperlipidemia in patients with type 2 diabetes
      mellitus].
AB  - Thirty five patients with type 2 diabetes mellitus complicated by cardiovascular
      diseases received 6-month treatment for hyperlipidemia with poseidonol that
      represents a set of essential polyunsaturated fatty acids. This yielded good
      results as 11.6%-, 30%- and 24.2% decreases in the levels of cholesterol,
      triglycerides, and beta-lipoprotein, respectively, and a 9.9%- increase in alpha
      lipoprotein. Lipid metabolism became normal in 34.2% of the patients, the
      remaining had positive changes as normalization of 1 to 3 lipid parameters. The
      tolerance of the agent was good, no negative effect on hepatic and renal
      functions was found.

PMID- 11521382
TI  - [Choosing the dose of aprovel (irbesartan) in patients with chronic heart
      insufficiency].

PMID- 11521383
TI  - [Timely diagnosis of Marfan's syndrome].

PMID- 11521384
TI  - [Psychosomatic features in patients with essential hypertension].

PMID- 11521385
TI  - [Negative T wave in the 3rd standard ECG lead].

PMID- 11521386
TI  - [The peculiarity of ECG pattern in isolated right ventricular myocardial
      infarction].

PMID- 11521387
TI  - [Side effects of glucocorticosteroid therapy in a patient with bronchial asthma].

PMID- 11521388
TI  - [The Leopard syndrome in a patient with sebocystomatosis].

PMID- 11521389
TI  - [Hyperhomocysteinemia as a risk factor for cardiovascular disease].

PMID- 11521390
TI  - [Concomitant bifractionated radiotherapy and chemotherapy with cisplatin and 5
      fluorouracil in locally progressive, non-resectable epidermoid carcinomas of the
      pharynx: ten years experience at the Antoine Lacassagne center].
AB  - PURPOSE: Patients suffering from locally advanced unresectable squamous cell
      carcinoma of the oropharynx and hypopharynx treated with radiotherapy alone have
      a poor prognosis. More than 70% of patients die within 5 years mainly due to
      local recurrences. The aim of this study was to evaluate retrospectively the
      Antoine Lacassagne Cancer Center's experience in a treatment by concomitant bid
      radiotherapy and chemotherapy. Evaluation was based on analysis of the toxicity,
      the response rates, the survival, and the clinical prognostic factors. PATIENTS
      AND METHODS: From 1992 to 2000, 92 consecutive patients were treated in our
      single institution. All of them had stage IV, unresectable squamous cell
      carcinoma of the pharynx and they received continuous bid radiotherapy (two daily
      fractions of 1.2 Gy, 5 days a week, with a 6-h minimal interval between
      fractions). Total radiotherapy dose was 80.4 Gy on the oropharynx and 75.6 Gy on
      the hypopharynx. Two or three chemotherapy courses of cisplatin (CP)-5
      fluorouracil (5FU) were given during radiotherapy at 21-day intervals (third not
      delivered after the end of the radiotherapy). CP dose was 100 mg/m2 (day 1) and 5
      FU was given as 5-day continuous infusion (750 mg/m2/day at 1st course; 430
      mg/m2/day at 2nd and 3rd courses). Special attention was paid to supportive care,
      particularly in terms of enteral nutrition and mucositis prevention by low-level
      laser energy. RESULTS: Acute toxicity was marked and included WHO grade III/IV
      mucositis (89%, 16% of them being grade IV), WHO grade III dermatitis (72%) and
      grade III/IV neutropenia (61%). This toxicity was significant but manageable with
      optimised supportive care, and never led to interruption of treatment for more
      than 1 week, although there were two toxic deaths. Complete global response rate
      at 6 months was 74%. Overall global survival at 1 and 2 years was 72% and 50%
      respectively, with a median follow-up of 17 months. Prognostic factors for
      overall survival were the Karnofsky index (71% survival at 3 years for patients
      with a Karnofsky index of 90-100% versus 30% for patients with a Karnofsky index
      of 80% versus 0% for patients with a Karnofsky index of 60-70%, p = 0.0001) and
      tumor location (55% at 3 years for oropharynx versus 37% for panpharynx versus
      28% for hypopharynx, p = 0.009). CONCLUSION: These results confirm the efficacy
      of concomitant bid radiotherapy and chemotherapy in advanced unresectable tumor
      of the pharynx. The improvement in results will essentially depend on our
      capacity to restore in a good nutritional status the patients before beginning
      this heavy treatment.

PMID- 11521391
TI  - [Endometrial adenocarcinoma treated with combined radiotherapy and surgery: 437
      cases].
AB  - PURPOSE: To identify prognostic factors and treatment toxicity in a series of
      operable endometrial adenocarcinomas. PATIENTS AND METHODS: Between November 1971
      and October 1992, 437 patients (pts) with endometrial carcinoma, staged according
      to the 1988 FIGO staging system, underwent total abdominal hysterectomy and
      bilateral salpingo-oophorectomy without (n = 140) or with (n = 297) pelvic lymph
      node dissection. The chronology of RT was not randomized and depended on the
      usual practices of the surgical teams. Group I: 79 pts received preoperative
      uterovaginal brachytherapy (mean total dose [MD]: 57 Gy). Group II: 358 pts
      received postoperative RT (196 pts received vaginal brachytherapy alone [MD: 50
      Gy], 158 pts had external beam pelvis RT [EPRT] [MD: 46 Gy over 5 weeks] followed
      by vaginal brachytherapy [MD: 17 Gy], and 4 pts had EPRT alone [MD: 46 Gy over 5
      weeks]). The mean follow-up was 128 months. RESULTS: The 10-year disease-free
      survival rate was 86%. From 57 recurrences, 12 were isolated locoregionally.
      Multivariate analysis showed that independent factors decreasing the probability
      of disease-free survival were: histologic type (clear cell carcinoma, p = 0.038),
      largest histologic tumor diameter > 3 cm (p = 0.015), histologic grade (p =
      0.008), myometrial invasion > 1/2 (p = 0.0055), and 1988 FIGO staging system (p =
      9.10(-8)). In group II, the addition of EPRT did not seem to improve locoregional
      control. The postoperative complication rate was 7%. The independent factors
      increasing the risk of postoperative complications were FIGO stage (p = 0.02) and
      pelvic lymph node dissection (p = 0.011). The 10-year rate for grade 3 and 4 late
      radiation complications according to the LENT-SOMA scoring system was 3.1%. EPRT
      independently increased the 10-year rate for grade 3 and 4 late radiation
      complications (R.R.: 5.6, p = 0.0096). CONCLUSION: EPRT increases the risk of
      late radiation complications. After surgical and histopathologic staging with
      pelvic lymph node dissection, in a subgroup of intermediate risk patients (stage
      IA grade 3, IB-C and II), postoperative vaginal brachytherapy alone is probably
      sufficient to obtain a good therapeutic index. Results for patients with stage
      III tumor are not satisfactory.

PMID- 11521392
TI  - [Management of breast cancer in Madagascar].
AB  - PURPOSE: Retrospective analysis of management and outcome of breast cancer in
      Madagascar. PATIENTS AND METHODS: From January 1996 to December 1998, 259 women
      with breast cancer were seen in the only department of oncology of the island,
      located in Antananarivo. It is equipped with a cobalt unit (unavailable in 1996).
      There was no uniform policy on surgery. Chemotherapy and hormonotherapy were not
      available for all patients. Reduced equipment enabled a minimal pre-therapeutic
      workshop. RESULTS: Mean age was 48.5 years. One hundred and fifty-six women were
      premenopausal. The majority (69%) lived less than 50 km from the department.
      Tumours were at an advanced stage in 67% of the cases; the mean delay for
      diagnosis was 9.4 months. Treatments were done with curative intent in 118 cases
      and with palliative intent in 64 cases. Partial surgery (89) was adequate in
      40.5% of the cases; total mastectomy concerned 94 women. Axillary lymph node
      dissection was done in 94 cases and was positive in 76 cases. The number of
      involved nodes was noticed in 47 cases. Curative radiotherapy concerned 106
      patients, 41 after total mastectomy and 44 after lumpectomy, and was exclusive in
      21 cases. Palliative irradiation was done locally with hypofractionation for 35
      patients. Chemotherapy was performed in 86 women. The 4-year survival of the 136
      assessable patients was 73%. CONCLUSION: Improvement in breast cancer treatment
      outcome in Madagascar is the result of earlier diagnosis of the disease.
      Information and education of the population together with caregivers are
      necessary, because updating and improving technical equipment is not currently
      possible due to the economic problems that the country has to face.

PMID- 11521393
TI  - [Standards, Options and Recommendations for the management of stage I or II
      primary bronchial cancers treated exclusively with radiotherapy].
AB  - CONTEXT: The 'Standards, Options and Recommendations' (SOR) project, started in
      1993, is a collaboration between the Federation of the French Cancer Centres
      (FNCLCC), the 20 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 outcome for cancer patients. The methodology is based on literature review
      and critical appraisal by a multidisciplinary group of experts, with feedback
      from specialists in cancer care delivery. OBJECTIVES: To develop clinical
      practice guidelines according to the definitions of the Standards, Options and
      Recommendations project for the management of stage I and II non small cell lung
      carcinoma treated by radiotherapy alone. METHODS: Data were identified by
      searching Medline and personal reference lists of members of the expert groups.
      Once the guidelines were defined, the document was submitted for review to
      independent reviewers, and to the medical committees of the 20 French cancer
      centres. RESULTS: The main recommendations for the management of stage I and II
      non small cell lung carcinoma treated by radiotherapy alone are: 1) The curative
      external irradiation with a continual course is an alternative to surgery only in
      the case of medically inoperable tumors or because the patient refuses surgery;
      2) The external irradiation of the primary tumor only without the mediastinum
      could be proposed in peripheral stage IA. In proximal stage IA and IB, external
      irradiation should be carried out only as part of prospective randomised
      controlled trials comparing a localised irradiation of the primary tumor with a
      large irradiation of the mediastinum and the primary tumor. The treated volume
      must include the macroscopic tumoral volume with or without the microscopic
      tumoral volume and with a security margin from 1.5 to 2 cm; 3) There is a benefit
      to delivering a total dose in the primary tumor higher than 60 Gy in so far as
      the proposed irradiation, taking into account the respiratory function, does not
      increase the likelihood of severe adverse events due to radiation; and 4) The
      change in fractionation, the radiochemotherapy combination, the endobronchial
      brachytherapy with high dose rate alone or with external irradiation could be
      proposed only as part of prospective controlled trials for tumors classified as
      stage IB or II.

PMID- 11521394
TI  - Communication ecology of webbing clothes moth: 1. Semiochemical-mediated location
      and suitability of larval habitat.
AB  - We tested two hypotheses: 1) that there is semiochemical-mediated attraction of
      male and female webbing clothes moth (WCM), Tineola bisselliella (Hum.)
      (Lepidoptera: Tineidae) to suitable larval habitat; and 2) that selection of
      optimal larval habitat has fitness consequences. In binary or ternary choice
      arena bioassay experiments that prevented WCM from contacting test stimuli, males
      and females were attracted to dried but untanned animal pelts (red squirrel,
      muskrat, beaver, coyote, red fox and bobcat) and preserved horseshoe crab but not
      to unprocessed sheep's wool, demonstrating semiochemical-based recognition of,
      and discrimination between, potential larval habitats. Selection of habitat has
      fitness consequences for ovipositing females, because significantly more male and
      female WCM completed development when the larval diet consisted of intact animal
      pelt (hide plus hair) rather than hide or hair alone. Equal attraction of male
      WCM to muskrat pelt volatiles in Porapak Q or solvent extracts of muskrat pelts
      indicated that volatile semiochemicals could be obtained by both methods.

PMID- 11521395
TI  - Communication ecology of webbing clothes moth: 2. Identification of
      semiochemicals mediating attraction of adults to larval habitat.
AB  - Our objective was to identify the semiochemicals that mediate attraction of the
      webbing clothes moth (WCM), Tineola bisselliella (Lepidoptera: Tineidae), to
      suitable larval habitat. Coupled gas chromatographic-electroantennographic
      detection (GC-EAD) analyses of Porapak Q-captured bioactive volatiles from
      horseshoe crab, and dried but untanned vertebrate pelts revealed numerous EAD
      active volatiles. These volatiles were identified by comparative GC-mass
      spectrometry and GC-EAD analyses of natural and synthetic compounds. A blend of
      28 synthetic candidate semiochemicals attracted both male and female WCM.
      Experiments deleting various components determined that saturated aldehydes--but
      not unsaturated aldehydes, saturated hydrocarbons, saturated alcohols, or ketones
      -were essential for blend attractiveness. A blend of nonanal, the single most
      attractive aldehyde, in combination with geranylacetone was more attractive to
      WCM than the 28-component blend or dried, untanned animal pelt. Selection of
      larval habitat resides more with male than female WCM, as indicated by stronger
      EAD responses from male than female antennae to habitat-derived semiochemicals,
      and more selective and early response to habitat cues by males than females.
      Exploitation of nonanal and geranylacetone as resource-derived semiochemicals by
      both adult WCM and its larval parasitoid, Apanteles carpatus, is an example of
      convergent semiochemical parsimony.

PMID- 11521396
TI  - Capture rates of the European pine sawfly, Neodiprion sertifer, in pheromone
      traps, with special regard to effects of wind speed.
AB  - Males of the European pine sawfly, Neodiprion sertifer Geoffr., were marked and
      released downwind from pheromone traps, baited with 100 micrograms of the sex
      pheromone (2S,3S,7S)-3,7-dimethyl-2-pentadecyl acetate. Males were released 5 m
      downwind from one trap, or downwind from five traps, 50 m or 200 m away. The
      average capture rates after 24 hr were 21.5%, 17.7% and 3.8%, respectively. The
      capture rate was highest at moderate wind speeds (1-2 m/sec) in the 50 m
      experiments, whereas it decreased above wind speeds of 1.5 m/sec in the 200 m
      experiments. With no precipitation and > 13.5 degrees C during overcast, wind
      speed is presumably the most important climatic factor for N. sertifer males
      flying upwind to a pheromone source. Travel time, the elapsed time form take-off
      to landing on the trap, varied considerably, and the shortest recorded travel
      times were 1, 6 and 45 min for the 5, 50, and 200 m experiments, respectively.
      The trap efficiency i.e., number of captured males per number of males that
      landed on the trap, was estimated at 52% in the 5 m experiments. The sampling
      range after 24 hr was calculated at approximately 400 m by regression analysis.
      The combination of the males' flight ability during upwind progress and their
      longevity (12 days), suggests a potentially large seasonal sampling range of the
      traps used in this study.

PMID- 11521397
TI  - Dual chemical barriers protect a plant against different larval stages of an
      insect.
AB  - The host plants of the native American butterfly, Pieris napi oleracea, include
      most wild mustards. However, garlic mustard, Alliaria petiolata, a highly
      invasive weed that was introduced from Europe, appears to be protected from this
      insect. Although adults will oviposit on the plant, most larvae of P. n. oleracea
      do not survive on garlic mustard. We used feeding bioassays with different larval
      stages of the insect to monitor the isolation and identification of two bioactive
      constituents that could explain the natural resistance of this plant. A novel
      cyanopropenyl glycoside (1), alliarinoside, strongly inhibits feeding by first
      instars, while a flavone glycoside (2), isovitexin-6"-D-beta-glucopyranoside,
      deters later instars from feeding. Interestingly, the first instars are
      insensitive to 2, and the late instars are little affected by 1. Furthermore,
      differential effects of dietary experience on insect responses suggest that 1
      acts through a mechanism of post-ingestive inhibition, whereas 2 involves
      gustatory deterrence of feeding.

PMID- 11521398
TI  - Seasonal and population variation in flavonoid and alliarinoside content of
      Alliaria petiolata.
AB  - Pieris napi oleracea, an indigenous butterfly in North America, lays eggs on
      Alliaria petiolata, an invasive weed that was introduced from Europe. However,
      larval development on plants from different sources varies considerably. A.
      petiolata is a compulsive biennial, and its foliage is rich in apigenin
      flavonoids. We compared the chemistry of different vegetative forms from
      different populations in the vicinity of Ithaca, NY throughout the year.
      Significant differences occurred in the number of apigenin derivatives in
      different populations and vegetative forms, and seasonal variations in the
      amounts of these compounds were found. We have previously isolated two major
      compounds, alliarinoside [(2Z)-4-(beta-D-glucopyranosyloxy)-2-butenenitrile] (1)
      and isovitexin-6-O"-beta-D-glucoside (3), which negatively affect development of
      P. napi oleracea larvae. Comparative analyses of these compounds in two
      populations throughout the year showed that their concentrations reached maxima
      twice annually. Foliage is almost devoid of flavonoids in June-July. Thus,
      variation in the chemistry of the plant may account for observed variation in
      development rates and survival of the larvae. Several apigenin compounds were
      isolated and identified by spectral studies.

PMID- 11521399
TI  - Differences in host use efficiency of larvae of a generalist moth, Operophtera
      brumata on three chemically divergent Salix species.
AB  - The food selection, growth, and fecundity of insect herbivores are largely
      dictated by the chemical composition and nutritive values of plant foliage. We
      studied the host-use efficiency of larvae of the generalist moth, Operophtera
      brumata (Lepidoptera: Geometridae) on three chemically divergent but nutritively
      similar willows (Salix spp.). The 4th instars were able to use the salicylate
      free leaves of S. phylicifolia efficiently. Growth was slightly reduced on S.
      pentandra, which contained a moderate level of acetylated salicylates. The high
      concentration of salicylates found in the leaves of S. myrsinifolia seemed to
      provide efficient protection against non-specialized O. brumata. We also studied
      assimilation of nutrients and degradation of salicylates and other secondary
      compounds in the digestive tract of O. brumata larvae. Neither the assimilation
      of nitrogen nor of carbon were affected by secondary chemicals of ingested food.
      Salicylates were shown to be degraded to salicin and catechol, while further
      degradation of salicin to saligenin was rather slow. In an artificial diet
      experiment, we showed that two degradation products of salicylates, catechol and
      saligenin markedly reduced the growth of the larvae. Neither salicin nor
      chlorogenic acid affected larval growth. We conclude that salicylates reduced the
      growth of the generalist winter moth mainly by feeding deterrence caused by 6
      hydroxy-2-cyclohexenone and catechol. Compared to the deleterious effects of
      salicylates the effects of other secondary compounds were minor.

PMID- 11521400
TI  - Evaluation of vetiver oil and seven insect-active essential oils against the
      Formosan subterranean termite.
AB  - Repellency and toxicity of 8 essential oils (vetiver grass, cassia leaf, clove
      bud, cedarwood, Eucalyptus globules, Eucalyptus citrodora, lemongrass and
      geranium) were evaluated against the Formosan subterranean termite, Coptotermes
      formosanus Shiraki. Vetiver oil proved the most effective repellent because of
      its long-lasting activity. Clove bud was the most toxic, killing 100% of termites
      in 2 days at 50 micrograms/cm2. The tunneling response of termites to vetiver oil
      also was examined. Vetiver oil decreased termite tunneling activity at
      concentrations as low as 5 micrograms/g sand. Tunneling and paper consumption
      were not observed when vetiver oil concentrations were higher than 25
      micrograms/g sand. Bioactivity of the 8 oils against termites and chemical
      volatility were inversely associated. Listed in decreasing order of volatility,
      the major constituents of the 8 oils were: eucalyptol, citronellal, citral,
      citronellol, cinnamaldehyde, eugenol, thujopsene, and both alpha- and beta
      vetivone. Vetivor oil is a promising novel termiticide with reduced environmental
      impact for use against subterranean termites.

PMID- 11521401
TI  - Zanthoxylum piperitum, an Asian spice, inhibits food intake in rats.
AB  - We investigated the effects of a total extract from Zanthoxylum piperitum fruit,
      of the volatile components of extract, and of a non-volatile fraction containing
      the major alkylamides of Zanthoxylum (NVA) on food intake in rats. In Experiment
      1, three groups (A, B, C) of mildly food deprived rats were given one hour long
      feeding trials during which they were offered choices between an oat-bran wafer
      paired with vegetable oil and a wafer paired with a Zanthoxylum preparation in
      vegetable oil. Trials were divided into three blocks of two tests each. During
      Blocks 1 and 3, two wafers coated with vegetable oil were offered to establish
      baseline consumption. During Block 2, Group A was given choices between wafers
      coated with oil and wafers coated with total extract. Group B was offered oil
      coated wafers and wafers coated with the NVA fraction. Group C received two oil
      coated wafers. One was served on top of a screened dish containing a sample of
      total extract. In this manner, the rats were exposed to volatile compounds
      emanating from the extract but could not contact the extract. The second wafer
      was served on top of a screened sample of oil. RESULTS: In Blocks 1 and 3 trials,
      the rats fed indiscriminately from both wafers. During Block 2, total extract,
      the NVA fraction and the volatile compounds from extract all significantly
      reduced food consumption. In Experiment 2, habituation to the NVA fraction and to
      the volatile constituents of extract was examined in two additional groups (D,
      E), using the methods described above. Baseline consumption was tested in Blocks
      1 and 3 by offering two oil coated wafers. During Block 2, group D was given 10
      trials with oil coated and NVA-fraction coated wafers. Group E was given 10
      trials with oil coated wafers paired with the volatile constituents of total
      extract and with those of oil. RESULTS: Both groups failed to habituate to the
      Zanthoxylum stimuli. Wafers treated with the NVA fraction and wafers paired with
      the volatile constituents of extract were avoided throughout the 10 test days.

PMID- 11521402
TI  - Are chemical alarm cues conserved within salmonid fishes?
AB  - A wide diversity of fishes possess chemical alarm signalling systems. However, it
      is not known whether the specific chemicals that act as alarm signals are
      conserved within most taxonomic groups. In this study we tested whether cross
      species responses to chemical alarm signals occurred within salmonid fishes. In
      separate laboratory experiments, we exposed brook charr (Salvelinus fontinalis),
      brown trout (Salmo trutta), and rainbow trout (Oncorhynchus mykiss) to chemical
      alarm signals from each of the three salmonid species and from swordtails
      (Xiphophorus helleri). In each case, the test species responded with appropriate
      antipredator behavior to all three salmonids alarm cues, but did not react to
      swordtail cues. These data suggest that chemical alarm cues are partially
      conserved within the Family Salmonidae. For each species tested, the intensity of
      the response was stronger to conspecific alarm cues, than to heterospecific alarm
      cues, indicating that salmonids could distinguish between chemical cues of
      conspecifics versus heterospecifics. These results suggest that the chemical(s)
      that act as the alarm cues may be: 1) identical and that there may be other
      chemical(s) that allow the test fish to distinguish between conspecifics and
      heterospecifics, or 2) that the cues that act as signals are not identical, but
      are similar enough to be recognized.

PMID- 11521403
TI  - Attack cone avoidance during predator inspection visits by wild finescale dace
      (Phoxinus neogaeus): the effects of predator diet.
AB  - When confronted by potential predators, many prey fishes engage in predator
      inspection behavior. Previous authors have argued that by selectively avoiding
      the predator's head during an inspection visit (attack cone avoidance),
      individual inspectors may reduce their local risk of predation. In field trials,
      we investigated the effects of predator diet cues on the presence of 'attack cone
      avoidance' during predator inspection visits. Wild, free-ranging finescale dace
      (Phoxinus neogaeus) were exposed to the combined cues of a model predator and a
      distilled water control or the odor of a yellow perch (Perca flavescens) fed dace
      (with alarm pheromone), swordtail (Xiphophorus helleri) (lacking Ostariophysan
      alarm pheromone), or perch that were food deprived for four days. Finescale dace
      modified their predator inspection behavior following exposure to the odor of a
      perch fed dace (fewer dace present, reduced frequency of inspections, and an
      increased per capita inspection rate) compared to those exposed to the odor of a
      perch fed swordtails, perch that were food deprived, or a distilled water
      control. In addition, dace inspected the tail region more often only when the
      model predator was paired with the odor of a perch fed dace. In all other
      treatments, dace inspected the head region of the model predator more often.
      These data suggest that attack cone avoidance of inspecting prey fishes may be
      more likely to occur in high-risk situations, such as in the presence of
      conspecific alarm pheromones in the diet of potential predators.

PMID- 11521404
TI  - Avoidance response of juvenile Pacific treefrogs to chemical cues of introduced
      predatory bullfrogs.
AB  - Bullfrogs (Rana catesbeiana), native to eastern North America, were introduced
      into Oregon in the 1930's. Bullfrogs are highly efficient predators that are
      known to eat a variety of prey including other amphibians. In laboratory
      experiments, we investigated whether juvenile Pacific treefrogs (Hyla regilla)
      recognize adult bullfrogs as a predatory threat. The ability of prey animals to
      acquire recognition of an introduced predator has important implications for
      survival of the prey. We found that treefrogs from a population that co-occurred
      with bullfrogs showed a strong avoidance of chemical cues of bullfrogs. In
      contrast, treefrogs from a population that did not co-occur with bullfrogs, did
      not respond to the bullfrog cues. Additional experiments showed that both
      populations of treefrogs use chemical cues to mediate predation risk. Treefrogs
      from both populations avoided chemical alarm cues from injured conspecifics.

PMID- 11521405
TI  - Chemical composition of precloacal secretions of Liolaemus lizards.
AB  - Interspecific chemical variation of precloacal pore secretions of Liolaemus
      lizards was characterized in 20 species, and intraspecific chemical variation was
      characterized using nine individuals of L. bellii. The latitude (Chile, 18
      degrees to 33 degrees South latitude) and altitude (100 to 4350 m.a.s.l.) of the
      capture sites were recorded, as well as the number of precloacal pores of each
      lizard. Secretions were analyzed by GC-MS. A total of 49 compounds were found
      distributed among the 20 species of Liolaemus. Different chemical patterns
      occurred at intra- and interspecific levels. Compounds belonged to three main
      families: n-alkanes, long chain carboxylic acids, and steroids. Cholesterol and
      five carboxylic acids (tetradecanoic, hexadecanoic, hexadecenoic, octadecanoic,
      and Z-9-octadecenoic) appeared in all species. The number of precloacal pores
      correlated positively with altitude and negatively with latitude, suggesting that
      lizards produce more secretions under harsh environments.

PMID- 11521406
TI  - Allelochemicals in wheat (Triticum aestivum L.): production and exudation of 2,4
      dihydroxy-7-methoxy-1,4-benzoxazin-3-one.
AB  - An analytical technique employing gas chromatography and tandem mass spectrometry
      (GC/MS/MS) was employed to systematically screen fifty-eight wheat accessions for
      their differential production of 2,4-dihydroxy-7-methoxy-1,4-benzoxazin-3-one
      (DIMBOA) from three consecutive sources, i.e., the shoots, roots, and in the
      associated agar growth medium (collected as root exudates) of 17-day-old wheat
      seedlings. DIMBOA content differed significantly in the shoots, roots, or in the
      agar growth medium between accessions. DIMBOA accumulated differentially within
      the plant, with roots containing more DIMBOA than the shoots. Only 19% of
      accessions were able to exude DIMBOA from living roots into their growth medium,
      indicating the exudation of DIMBOA is accession-specific. DIMBOA level in root
      tissues is expected to be high when a high level of DIMBOA content is detected in
      the shoots. Wheat seedlings did not release detectable amounts of DIMBOA when the
      DIMBOA level was low in the root tissues. The valuable genetic material with high
      levels of DIMBOA in the shoots or roots identified in the present research could
      be used to breed for wheat cultivars with elevated allelopathic activity.

PMID- 11521407
TI  - Methodological setup to study allelochemical translocation in radish seedlings.
AB  - [Ring-U14C] p-hydroxybenzoic acid (POH) translocation during radish germination
      and early seedling growth was studied to compare two culture conditions
      (sterile/non-sterile) and two modes of POH extraction (ethanol/oxidizing).
      Quantification of POH in organs was performed by grinding them in a mortar with
      ethanol or by combusting them in a biological oxidizer. Comparison of these
      extraction methods revealed that the oxidizer provides higher POH concentrations
      than grinding. Uptake and translocation of POH into radish seedlings occurred in
      the first 24 hr with the highest accumulation in cotyledons. POH in cotyledons
      ranged from 8 to 12.4 mumol g-1 FW. Two forms of POH were found in seedlings, an
      ethanol-soluble one and a "bound" one. After 96 hr incubation, half of the
      recovered POH was "bound" in roots and hypocotyls. POH recovery in seedlings was
      also higher under axenic rather than non-axenic conditions. POH was degraded into
      14CO2 by microorganisms under non-sterile cultures, its concentration in culture
      medium decreased from 10(-3) to 10(-4) M between the first and the fourth day of
      incubation. Choice between sterile and non-sterile culture conditions as a method
      depends on particular research objectives. Non-sterile methods can be used to
      reflect natural processes whereas sterile methods can be used if the objective is
      to determine allelochemical penetration and biological effects on target plants.

PMID- 11521408
TI  - Women and coronary heart disease.
AB  - Coronary heart disease (CHD) is the leading cause of death in men and women in
      the United States. The incidence of CHD during midlife is lower in women than
      men, but the gap narrows with each decade. Because women have a longer life span
      than men, the absolute numbers of CHD deaths are roughly equal. Effective
      diagnosis of CHD in women requires the recognition of gender differences in
      presentation and pathogenesis. Women present with atypical symptoms and are less
      likely to have adequate primary prevention. This article discusses the
      differences between men and women in CHD and examines the assessment, diagnosis,
      and clinical management of CHD in women.

PMID- 11521409
TI  - Identifying poststreptococcal glomerulonephritis.
AB  - Expedient antimicrobial treatment of group A beta-hemolytic streptococcal
      tonsillopharyngitis prevents suppurative complications and rheumatic fever;
      however, timely therapy does not prevent acute poststreptococcal
      glomerulonephritis. Acute poststreptococcal glomerulonephritis is the most common
      form of postinfectious glomerulonephritis and a leading cause of acute and
      chronic renal failure in childhood. This article discusses clinical presentation,
      diagnostic workup, treatment, and prevention of poststreptococcal
      glomerulonephritis in adults and children in the primary care setting.

PMID- 11521411
TI  - The incompetent expert.

PMID- 11521410
TI  - Sjogren's syndrome: pathogenesis, diagnosis, and treatment.
AB  - Sjogren's syndrome (SS) is the most common autoimmune disorder among women.
      Symptoms occur when the infiltration of immune cells into the salivary and
      lacrimal glands causes a progressive decline in sight, smell, and taste. Although
      symptoms seriously disrupt quality of life, the disease's vague manifestations
      usually prevent individuals from seeking immediate help. By the time a diagnosis
      is rendered, significant systemic organ involvement may have occurred. Although
      there is no cure, clinician understanding of the epidemiology, etiology, and
      pathophysiology of SS enhances its symptomatic management in primary care
      settings.

PMID- 11521412
TI  - Forensic psychiatry and epidemiology: introduction.

PMID- 11521413
TI  - Mental disorder in federal offenders: a Canadian prevalence study.

PMID- 11521414
TI  - Childhood and adult victimization as risk factor for major depression.

PMID- 11521415
TI  - Criminal Justice System in Brazil: functions of a forensic psychiatrist.

PMID- 11521416
TI  - Forensic psychiatry services in Australia.

PMID- 11521417
TI  - Characteristics of psychiatric inpatients detained under civil commitment
      legislation: a Canadian study.

PMID- 11521418
TI  - Mental disturbances and criminological characteristics in crime-accused insane as
      recorded at the Judiciary Office in La Plata, Argentina, for 10 years.

PMID- 11521419
TI  - The major mental disorders and crime: stop debating and start treating and
      preventing.

PMID- 11521420
TI  - Delinquency and health among adolescents: multiple outcomes of a similar social
      and structural process.

PMID- 11521421
TI  - Reinforcing stereotypes: how the focus on forensic cases in news reporting may
      influence public attitudes towards the mentally ill.

PMID- 11521422
TI  - Patterns and mental health predictors of domestic violence in the United States:
      results from the National Comorbidity Survey.

PMID- 11521423
TI  - Redevelopment of forensic-psychiatric institutions in former East Germany.

PMID- 11521424
TI  - Impact of legal reforms on length of forensic assessments in Alberta, Canada.

PMID- 11521425
TI  - Gender differences in risk factors for violent behavior among economically
      disadvantaged African American and Hispanic young adolescents.

PMID- 11521426
TI  - [Effectiveness of bio-regulators in the treatment of diabetic retinopathy].
AB  - Treatment of diabetic retinopathy remains a most important problem of modern
      ophthalmology. Bioregulatory therapy has been widely used in recent years as one
      of promising trends in clinical medicine. The purpose of this study was to
      evaluate the efficiency of peptide bioregulators in combined treatment of
      diabetic retinopathy. A total of 104 patients were administered bioregulatory
      therapy (retinal preparation retinalamine, epiphysis preparation epithalamine,
      cerebral cortex preparation cortexine,) and 42 patients were controls. Peptide
      bioregulators in 90% cases promoted improvement of vision acuity, improved the
      ophthalmoscopic picture of the fundus oculi (resolution of hemorrhages,
      plasmorrhages, decreased macular edema) and in all cases improved the functional
      activity of the retina and retinal bloodflow. No negative changes in the clinical
      picture were observed after peptide bioregulators in any of the cases. Peptide
      bioregulators normalized carbohydrate metabolism (sugar level and glycosylated
      hemoglobin in the blood), phagocytosis, and improved the subjective well-being of
      patients. Hence, the data indicate a pathogenetic effect of this therapeutic
      method and its good prospects in ophthalmology.

PMID- 11521427
TI  - [Possibilities of photorefraction surgery in patients with subclinical retinal
      detachment in myopia].
AB  - Peripheral retinal abnormalities detected in examinations of 4840 patients with
      myopia are analyzed. The incidence of subclinical detachments of the retina was
      8.7%. Two-staged laser therapy of detachments and its results are discussed and
      laser refraction operations in such abnormalities of the fundus oculi are
      considered. Results of photorefraction operations of different types in patients
      previously operated on the retina by the laser method are analyzed. Only 5
      patients needed repeated laser therapy on the fundus oculi during 3 years
      postoperation. Hence, photorefraction correction of refraction abnormalities can
      be carried out in patients with subclinical detachments of the retina after
      previous effective laser therapy.

PMID- 11521429
TI  - [Time course of visual functions in patients with pigmentary retinal degeneration
      after surgical treatment with biomaterial "Alloplant"].
AB  - The effects of operations using alloplant biomaterial on the time course of
      visual functions were evaluated in patients with pigmented degeneration of the
      retina in various terms after surgery. 198 patients with terminal and subterminal
      stages of pigmented degeneration of the retina were operated on by inserting
      alloplant into the suprachoroidal space, after which they were observed for 1, 2,
      and 3-5 years. Visual acuity, kinetic and static visual fields were measured and
      computer perimetry was carried out. Analysis of the results indicates that the
      operation making use of alloplant leads to statistically significant improvement
      of visual fields and visual acuity and to stabilization of these functions during
      the periods of observations in patients with subterminal and terminal stages of
      pigmented degeneration of the retina. These data allow us to regard the operation
      with alloplant as one of the methods inhibiting the development of pigmented
      degeneration of the retina and in some cases improving the visual function.

PMID- 11521428
TI  - [Induction of posterior detachment of the vitreous body by intraoperative vitreo
      syneresis with injection of water-soluble polymers (an experimental-morphological
      study)].
AB  - The capacity of water-soluble polymers (polyethylenimine, polyvinylpyrrolidone
      with copolymers) to induce posterior detachment of the vitreous by its rapid
      condensation (vitreosynerysis) was studied in experiments on 14 rabbits.
      Histological studies showed that water-soluble polymers specifically react
      forming complexes with components of the vitreous. The vitreous shrinks under the
      effect of polyelectrolytes (vitreosynerysis), which leads to its posterior
      detachment 1.5 h after injection of the polymer into the vitreous cavity:
      complete detachment was attained in 2 animals and partial in 8. The degree of
      vitreosynerysis depends on the complex-forming activity of polyelectrolytes
      towards the vitreous components. Polymers used in our study exerted no toxic or
      traction effects on the adjacent structures of the eye.

PMID- 11521430
TI  - [New methods of measuring the mobility of ocular prosthesis in anophthalmia and
      their comparative study].
AB  - Methods for measuring the mobility of ocular prostheses in patients with
      anophthalmia were developed and compared between each other and with the
      traditional Forster method for measuring the prosthesis mobility along perimeter.
      The most accurate method is measurement of the angle tangent (method No. 3),
      while Forster measurement is the least accurate and most subjective. The most
      rapid method is making use of millimeter pattern, which can be used in early
      terms after surgery in adults and children. All methods are convenient, simple,
      and require no special training.

PMID- 11521431
TI  - [Activity of lacrimal plasmin-like enzymes in the evaluation of the corneal state
      after photorefraction surgery].
AB  - Forty-three patients (58 eyes) were observed, who used contact lenses for a long
      time before photorefraction operations (photorefraction keratectomy and laser
      specialized keratomileusis--PRK and LASIK). Measurements of lacrimal plasmin-like
      enzymes (PLE) were carried out before and after operations on a Uniscan II
      microreader. Corneal and conjunctival intactness was evaluated by Bengal rose
      staining. Before surgery PLE activity was 3.5 times higher than normally in the
      patients using contact lenses. After PRK and LASIK, PLE activity increased and
      was 25% lower after LASIK than after PRK. Based on the data of preoperative
      diagnosis (Bengal rose test, measurement of PLE activities, Norn and Schirmer
      tests), the patients with contact lens intolerance without hypoproduction of
      tears are recommended rehabilitation treatment with drugs activating the repair
      processes (Vitacic, etc.), while patients with contact lens intolerance and tear
      hypoproduction are recommended low concentrations of viscoelastic drugs (Vismed).

PMID- 11521432
TI  - [Ultraviolet irradiation of blood in combined treatment of traumatic
      endophthalmitis].
AB  - Thirty-five patients (35 eyes) with traumatic endophthalmitis were treated.
      Ultraviolet exposure of autoblood was used in 16 patients, the rest 19 were
      treated routinely (antibiotics, etc.). Use of ultraviolet exposure of the blood
      in combined therapy of traumatic endophthalmitis more rapidly (12.6 vs. 22.1
      days) and effectively (93.7 vs. 68.4%) arrested intraocular infection and more
      often preserved the objective vision (31.3 vs. 10.5%).

PMID- 11521433
TI  - [Results of combined radiotherapy of choroid melanomas].
AB  - Method of combined radiotherapy of choroid melanomas, proposed by the authors,
      includes transscleral irradiation of the tumor by rutenium ophthalmoapplicators
      and simultaneous intracorporeal irradiation with 59Fe. Twenty-seven patients were
      treated. Morphological examination of enucleated eyes showed the capacity of 57Fe
      to incorporate in tumor cell, and observations indicate that this method of
      treatment not only extends the indications for organ-sparing radiotherapy of
      uveal melanomas, but delays the development of distant metastases as well.

PMID- 11521434
TI  - [Diagnostic possibilities of fine-needle aspiration biopsy in malignant tumors of
      the orbit].
AB  - Cytological studies were carried out in 94 patients with malignant tumors of the
      orbit using fine-needle aspiration biopsy. Diagnostic potentialities of the
      method are shown. The method possesses the highest diagnostic informative value
      in evaluation of the type of the process (98.8%). Cytological characteristics of
      the most incident malignant tumors of the orbit are presented.

PMID- 11521435
TI  - [Comparative study of the role of cytokines in various eye diseases. 2. Diabetic
      retinopathy].
AB  - The role of cytokines in the pathogenesis of diabetic retinopathy and mechanism
      of action of laser coagulation of the retina were investigated. A total of 110
      patients with insulin-dependent diabetes mellitus without clinical signs of
      diabetic retinopathy and at various stages of its development (subclinical,
      manifest preproliferative, and proliferative) were observed. Twenty-four of them
      were subjected to laser coagulation of the retina and/or vitrectomy. Control
      group consisted of 30 healthy donors. Ten cytokines (alpha-IFN, gamma-IFN, GM
      CSF, TGF-beta 1, Il-1, Il-4, Il-6, Il-6sR, TNF alpha) were measured in the serum,
      lacrimal fluid, and vitreous and subretinal fluid collected during operations.
      The data indicate that excessive or insufficient local and/or systemic production
      of at least seven cytokines (TNF alpha, gamma-IFN, Il-6, Il-pR, alpha-IFN, Il-8,
      and RGF-beta 1) can affect the retinal involvement in the pathological process
      and development of proliferative retinopathy in patients with insulin-dependent
      diabetes mellitus. The authors defined the criteria which can be used in clinical
      practice for predicting the manifestation of diabetic retinopathy, progress of
      the pathological process with formation of proliferative diabetic retinopathy,
      and the results of treatment by laser coagulation of the retina. The authors
      consider early immunorehabilitations of diabetics with the aim of preventing the
      development and progress of diabetic retinopathy a promising approach to
      treatment.

PMID- 11521436
TI  - [Fundamental principles of diagnosis, differential diagnosis and treatment of
      ocular tuberculosis].
AB  - Results of author's many-year studies of ophthalmic tuberculosis are presented. A
      method for verification of tuberculous origin and a system of diagnosis and
      differential diagnosis have been developed, which ensure a universal approach to
      diagnosis of ophthalmic tuberculosis and essentially reduce the incidence of
      erroneous diagnoses. Schemes for optimizing etiotropic drug therapy are proposed,
      decreasing the duration of the basic course to 6 months due to increase in the
      number of effective drugs during the initial phase of therapy to 3-4 and
      obligatory combination of systemic and local treatment. The incidence of
      tuberculosis in risk group is analyzed. Tasks of phthisioophthalmologists and
      ophthalmologists of outpatient health centers in detection and treatment of
      patients with ophthalmic tuberculosis are formulated.

PMID- 11521437
TI  - [Contusion ruptures of the cornea after radial keratotomy].
AB  - Eleven cases with corneal ruptures along keratotomic cicatrices after severe
      contusions are analyzed and one case is described in detail. These cases evidence
      a high probability of parting of keratotomic incision because of eyeball
      contusion. Contusion injuries of the eyes previously subjected to radial
      keratotomy are characterized by extremely severe clinical course and outcomes
      with poor functional results. Coarse alterations of ocular membranes, observed
      clinically and morphologically, lead to development of pronounced posttraumatic
      uveitis. This dictates special care in carrying out primary surgical treatment,
      massive antiinflammatory and resolving therapy. The outcome of such injuries
      depends mainly on the number of corneal cicatrices after keratotomy and on the
      direction of contusion.

PMID- 11521438
TI  - [Incidence of keratoconus and associated disability among adolescent conscripts
      in the Republic of Armenia].
AB  - Of 131 adolescents examined before military service in 1997-1999, group III
      disability for functional disorders of the eye was acknowledged in 14 and group
      II in 23 boys. Keratocone was associated with allergic conjunctivitis in 30.5%
      cases.

PMID- 11521439
TI  - [Dirofilariasis in the practice of an ophthalmologist].
AB  - A youth aged 16 was hospitalized in ophthalmological department for surgical
      treatment of the lower eyelid chalazion of the left eye. No helminths were
      diagnosed before surgery. Opening of the chalazion resulted in release of a
      thread-shaped helminth into the wound; the helminth was identified as immature
      Dirofilaria repens female. A solid connective tissue capsule formed round the
      parasite. Routes of Dirofilarias infection, its vectors, permanent, intermediate,
      and accidental hosts, and prevalence are discussed.

PMID- 11521440
TI  - [Use of preserved amniotic membrane for reconstruction of the surface of the
      anterior eye segment].

PMID- 11521441
TI  - [Pseudoexfoliation syndrome].

PMID- 11521442
TI  - [Use of ultrasonic method of examination in the diagnosis of retinopathy of
      prematurity].
AB  - A total of 164 children (328 eyes) aged 2 months to 3 years with stages L-V
      retinopathy neonatorum (RN) were examined. Ultrasonic examination of children
      with RN is an important accessory method in complex examination of the eyes in
      children with RN with exudative and fibrous changes of the vitreous and massive
      hemorrhages. Indications for the use of ultrasonic method of examination in
      children with RN are defined in order to evaluate the need in preventive laser or
      for kryocoagulation of the retina or diagnosis of retinal detachment in RN,
      particularly before surgery. This method helps predict the disease course and
      evaluate the time course of the process.

PMID- 11521443
TI  - [Topographic mapping of visual evoked potentials in the diagnosis of visual
      system diseases].

PMID- 11521444
TI  - [Clinical and functional characteristics of changes in the optic nerve in
      juvenile diabetic retinopathy].
AB  - A total of 611 patients (1222 eyes) with insulin-dependent diabetes mellitus
      which manifested at the age of 1-15 years were examined. Optic nerve was examined
      in 3 groups: 1) 177 students of Kharkov boarding school for diabetic children, 2)
      78 patients aged 6-18 years treated on an outpatient basis, and 3) 356 patients
      aged 20-54 years. Optic nerve involvement was detected 43.5 times more often in
      patients with proliferative diabetic retinopathy than in those with
      preproliferative diabetic retinopathy and 3 times more often in group 2 than in
      group 1. Chromatic visocontrastometry detected impaired spatial contrast
      sensitivity before manifestation of disorders in visual acuity and visual field.
      The earliest disorders in spatial contrast sensitivity were detected by red-white
      patterns.

PMID- 11521445
TI  - Brain interleukin-1 is involved in blood interleukin-6 response to immobilization
      stress in rats.
AB  - Interleukin (IL)-6, a cytokine for host defense responses to infection and
      inflammation, is known to be induced by non-invasive physical or psychological
      stress, too. To test possible involvement of brain IL-1 in the stress-induced IL
      6 production, IL-1 mRNA expression in the hypothalamus, in parallel with blood IL
      6 level, was examined in rats subjected to restriction of their movement
      (immobilization stress). When rats were immobilized, the hypothalamic IL-1 beta
      mRNA level was increased in 1 hr, followed by progressive rises in the serum IL-6
      level. The immobilization-induced rise in serum IL-6 was mimicked by
      intracerebroventricular (icv) administration of IL-1 beta under normal
      conditions, whereas it was attenuated by icv injection of an IL-1 receptor
      antagonist. These results indicate that IL-1 in the hypothalamus plays a pivotal
      mediating role in the stress-induced peripheral IL-6 production.

PMID- 11521446
TI  - Immunohistochemical demonstration of chromogranin A in endocrine organs of the
      rat and horse by use of region-specific antibodies.
AB  - Chromogranin A (CgA) is an acidic glycoprotein that is co-stored with hormones or
      neurotransmitters in granular components of endocrine cells and neurons, and
      released together with them in response to adequate stimulation. In addition to
      acting as a packaging protein, CgA functions as a precursor molecule that yields
      several bioactive peptides by proteolytic cleavage. The purpose of this study is
      to elucidate how different the processing of CgA is among endocrine tissues by
      immunostaining using multiple region-specific antisera, and to evaluate the
      availability of region-specific antisera. When various endocrine organs of rats
      were immunostained with four region-specific antisera against rat CgA (CgA 1-28,
      94-130, 296-314, and 359-389), all amine/peptide-secreting endocrine tissues
      except the pineal body were stained positively. The adrenal medulla and gastric
      endocrine cells were equally intensely immunoreactive to all four antisera, while
      the other endocrine tissues, represented by pancreatic islets, showed different
      staining patterns depending on the antiserum. These results suggest that the
      processing of CgA differs from tissue to tissue. An antiserum against horse CgA
      335-365, corresponding to rat CgA 359-389 which shows the highest concentration
      in the plasma and urine of the rat, again stained all endocrine tissues of the
      horse except the pineal body. Therefore, the anti-horse CgA 335-365 serum is
      useful for immunohistochemical survey of horse CgA, and may make possible the
      establishment of a CgA assay system for the measurement of CgA in the plasma,
      urine and saliva.

PMID- 11521447
TI  - Allina defies geography to boost CHF outcomes systemwide.

PMID- 11521448
TI  - National certification program helps doctors boost diabetes care.
AB  - A national certification program launched by the American Diabetes Association
      allows health plans and providers to distinguish themselves from the pack when it
      comes to caring for diabetics.

PMID- 11521449
TI  - Bridging the gaps in chronic illness care for children.
AB  - Most disease management programs target the health of populations, not
      individuals. That's a successful strategy in adults, particularly for the high
      cost, relatively high-frequency conditions such as heart disease and diabetes. A
      Seattle hospital is showing that the principles of disease management are
      effective even among children, where high-cost conditions are much less frequent.

PMID- 11521450
TI  - The effects of breastfeeding and birth spacing on infant and early childhood
      mortality in Ethiopia.
AB  - Research conducted in developing countries clearly demonstrates the positive
      effects of breastfeeding and widely spaced births on infant survival. The
      evidence is less clear as to whether these beneficial effects extend into early
      childhood, and under what conditions. In this paper we examine the effects of
      breastfeeding and birth spacing on neonatal, post-neonatal, and early childhood
      mortality in Ethiopia using data from the 1990 National Family and Fertility
      Survey. Our results provide clear evidence that the increased mortality risks
      associated with closely-spaced births continue beyond the first year of life into
      early childhood. Competition between siblings for food and maternal attention is
      the most probable explanation for this finding. We also find that breastfeeding
      beyond the second year of life is associated with higher mortality. Given that
      delayed weaning in Ethiopia is a common response to food shortages, we interpret
      this finding as further evidence of the negative consequences of resource
      deprivation for child survival.

PMID- 11521451
TI  - Association between maternal age at menarche and newborn size.
AB  - The impact of maternal age at menarche on newborn size was tested using data from
      4,996 single births taking place at Vienna, Austria, between 1985 and 1995--so
      called teenager pregnancies were excluded from the present analyses. All women
      experienced pregnancies between the ages of 19 to 42 years. Maturational time was
      related significantly to infant weight and length independent of maternal age and
      behavioral variables such as smoking. Early maturation, i.e., age at menarche
      before the 12th birthday, was significantly associated with decreased newborn
      weight and size. The incidence of low-weight newborns was significantly higher in
      early-maturing mothers. The more favorable nutritional status of women whose
      menarche occurred relatively early was not able to compensate for the negative
      effects of early maturation on intrauterine growth. Higher circulating estrogen
      levels in early maturers preserved into adulthood are discussed as possible
      reasons for intrauterine growth retardation of the offspring of early-maturing
      mothers.

PMID- 11521452
TI  - Are Jewish deathdates affected by the timing of important religious events?
AB  - Earlier studies reported a decline in September mortality in New York City and
      Budapest during years when Yom Kippur was in the interval September 28 through
      October 3, and fewer deaths among Californians with Jewish surnames during the
      week preceding Passover than during the week after Passover. These studies
      suggest that some Jews are able to postpone their deaths until after the
      celebration of an important religious event. We reexamine these findings using
      new data and find no statistically persuasive evidence that Jewish deaths decline
      before religious holidays. We do find an increase in deaths in the weeks shortly
      before and after birthdays.

PMID- 11521453
TI  - Canadian Indian mortality during the 1980s.
AB  - This study concerns itself with an investigation of general and cause-specific
      mortality differentials between Canadian Registered Indians (a subset of all
      aboriginals) and the larger Canadian population over two points in time, 1981 and
      1991. Multivariate analyses are executed separately across four segments of the
      life cycle: adulthood, infancy, early childhood and late childhood. With respect
      to adults, Indians share relatively high rates of suicide, homicide and
      accidental causes of death; over time, their conditional risks of death due to
      cancer and circulatory afflictions have gone up significantly. Mortality
      disadvantages for the Indians are also pronounced in infancy, early childhood
      (ages 1-4) and late childhood (ages 5-14). Suicide, accidents, and violence
      constitute serious problems among 5-14 year olds, while infectious/parasitic,
      respiratory and circulatory complications, plus accidents and violence, are
      principle killers in infancy. For children aged 1-4, respiratory problems and
      accidents/violence are prime causes of premature death. This less-than-optimal
      mortality profile is reflective of persistent problems associated with prolonged
      socioeconomic marginalization. The temporal pattern of change in
      chronic/degenerative disease mortality among adult Indians suggests a movement of
      this population toward a mature stage of epidemiological transition.

PMID- 11521454
TI  - Fecundity of daughters born after short, intermediate, or long birth intervals.
      An analysis of family reconstitutions from The Netherlands, late 19th-early 20th
      century.
AB  - In an historical cohort study, we compared the reproductive performances of women
      born after short (< 14 completed months), intermediate (21-32 completed months),
      and long (> 39 completed months) birth intervals. Of the initial study base,
      comprising family reconstitutions of 1,425 women born between 1873 and 1902 in or
      around Rotterdam (The Netherlands) and married before age 45, a large portion
      (data of 1,001 women born between 1888 and 1902) was uninformative because of
      (unintended) selection on birth control behavior. Among the remaining 424 women,
      those born after very short birth intervals (less than 1 year) showed higher
      likelihood of childlessness and stillbirth in the offspring than those born after
      intermediate intervals (adjusted odds ratios (OR) and 95%-confidence intervals:
      7.7 [1.8-33.0] and 3.3 [1.3-8.3], respectively). The latter association, however,
      nearly disappeared after restriction to women whose preceding sibling lived at
      least 1 year. Women born after modestly short intervals (12-13 months) exhibited
      longer interpregnancy intervals. So did women born after long birth intervals,
      but this might well be attributable to intergenerational transmission of
      reproductive behavior. These results indicate that fecundability is reduced in
      women born after short birth intervals.

PMID- 11521455
TI  - The age pattern of fecundability: an analysis of French Canadian and Hutterite
      birth histories.
AB  - This paper analyzes the age pattern of effective fecundability from populations
      with no evidence of deliberate fertility control using a new convolution model of
      fecundability. The analysis is based on a sample of Hutterite birth histories
      from the mid-20th century, and birth histories of French Canadians from the 17th
      and 18th centuries. The main findings are as follows: 1) the level of effective
      fecundability is higher among the French Canadians compared to the Hutterites; 2)
      effective fecundability peaks at age 20 for the Hutterites, and in the early to
      mid-20s for the French Canadians; 3) Hutterite effective fecundability declines
      almost linearly from age 20 to 45, and French Canadian effective fecundability
      declines slowly from its peak to the early 30s, and more rapidly at older ages;
      and 4) the duration of postpartum amenorrhea is longer for the French Canadians
      than for the Hutterites. Because of the shorter periods of postpartum amenorrhea
      the Hutterites have about the same average number of children as the French
      Canadians, even though the French Canadians have higher effective fecundability.

PMID- 11521456
TI  - Determinants of current use of contraception and children ever born in Nepal.
AB  - This paper explores the extent to which women's work for earnings, education and
      couple communication over family planning influence current contraceptive use and
      children ever born in Nepal. Data came from the 1996 Nepal Family Health Survey.
      The findings indicate that education has a significant positive influence on
      current use of contraception and a significant negative influence on children
      ever born. There was virtually no relationship between women working and current
      use of contraception. However, in full models, there was a significant positive
      relationship for women who earn cash for work on current use and a significant
      negative relationship for children ever born. Working alone does not increase
      contraceptive use or reduce the number of children ever born in Nepal, but
      earning cash for work does. The husband/couple variables also proved to be
      important determinants of current use of contraception and children ever born.

PMID- 11521457
TI  - The impact of fertility intentions on behavior: the case of sterilization.
AB  - In this paper, we take a new approach to the question of whether or not
      intentions regarding future fertility affect fertility-related behavior. Our
      approach has three principal features: 1) it takes sterilization as its outcome,
      rather than pregnancy or birth; 2) it is based on a conceptual model in which
      fertility-related behavior is seen as determined by a long-range planning
      process, modified by unanticipated life course contingencies; and 3) it uses data
      on desired total family size. Using data from the National Survey of Families and
      Households, we find that achieving one's desired parity has a strong, persistent,
      and positive effect on the probability of sterilization, supporting our view of
      the long-term nature of fertility intentions. People do modify their behavior in
      the face of unanticipated contingencies, but those effects are unexpectedly
      small.

PMID- 11521458
TI  - Race and the inheritance of low birth weight.
AB  - This paper uses intergenerational data from the Panel Study of Income Dynamics
      (PSID) to address the black-white difference in propensities toward low birth
      weight (LBW). We determine that socioeconomic conditions account for some
      variation in low birth weight across race. Further, while race differences in the
      risk of low birth weight cannot be explained entirely, we find that the
      inheritance of parental birth weight status dramatically reduces the black-white
      gap in low birth weight. Intergenerational legacies of poor infant health explain
      the largest share of racial disparities in filial birth weight. We then try to
      assess whether this intergenerational transmission of low birth weight is indeed
      genetic by using grandparent-fixed effects models to factor out, to a great
      extent, family socioeconomic circumstances. We find that even within this
      framework, both father's and mother's birth weight status have an important
      impact on filial outcomes. However, the degree of inheritance is weaker for
      African Americans than for other races. Finally, we theorize that the importance
      of paternal birth weight status implies a genetic association that does not work
      through the uterine environment but rather through the fetus itself.

PMID- 11521459
TI  - Breastfeeding behavior and infant survival with emphasis on reverse causation
      bias: some evidence from Nigeria.
AB  - The possibility of selection bias in the estimation of the effects of
      breastfeeding on subsequent survival is implied by the clinical evidence that
      children who are healthier at birth are more likely to be breastfed than their
      less healthy counterparts who may be prone to difficulties in sustaining
      breastfeeding. This paper addresses an important problem in understanding the
      association of breastfeeding and child survival with regard to reverse causation.
      It utilizes data on the reported reason for weaning to assess the degree to which
      reverse causality may be responsible for observed associations. The analysis
      indicates that children who are weaned in the neonatal period because of illness
      or weakness to suckle, experience a much higher risk of dying than others. This
      is not mainly because of the cessation of breastfeeding, but because of the
      original factor, being their illness. Any biases imparted by an initial selection
      mechanism appear, therefore, to have influence on the effectiveness of
      breastfeeding behavior.

PMID- 11521460
TI  - Index of lipid peroxidation and glucose utilization in the cerebrospinal fluid in
      patients with cerebral infarction.
AB  - Cerebral ischemia could be observed as acute metabolic crisis, when oxygen and
      glucose supply is compromised and synthesis of energy is insufficient. Apart from
      the excitotoxicity, increased production of reactive oxygen species with
      consequent lipid peroxidation is also included in neuronal cell damage.
      Furthermore, these toxic compounds could also be produced during the process of
      secondary inflammation of ischemic tissue. In the early stage of ischemia, as a
      systemic response to acute stress, there is an increase in glucose level in
      cerebrospinal fluid (CSF) and peripheral blood. According to the metabolic crisis
      and acidosis in ischemic brain tissue we investigated index of lipid peroxidation
      (ILP) and glucose utilization (IGU) in CSF of 53 patients of both sexes, aged 55
      70 years with cerebral infarction. Control group comprised 15 patients with
      sudden onset of motor deficit subjected to diagnostic lumbar radiculography and
      suspected on discal genesis. ILP in CSF, as the indicator and sequela of neuronal
      cell membranes damage, was two fold increased in the acute period of cerebral
      infarction and maximal values (3.5 times) were noticed 24 hours after the
      ischemic episode compared to controls. Besides the increase in glucose
      concentration in peripheral blood and CSF of patients with cerebral infarction,
      IGU was decreased (37%) with minimal values (32%) 24 hours after the ischemia.
      These changes indicate that glucose is available but cells are incapable to
      metabolize it. We concluded that ILP and IGU in CSF of patients with cerebral
      infarction could be indicators of metabolic dysfunction and neuronal cell damage.
      Also, these results suggest the significance of polyvalent therapy including
      antioxidative and antiinflammatory agents in acute phase of cerebral ischemia.

PMID- 11521461
TI  - Variability of haptoglobin and alpha 2-macroglobulin in Albino Oxford and Dark
      Augustin inbred strains of rats before and after trauma.
AB  - Increased synthesis of acute-phase proteins (APP) in the liver represents the
      most prominent aspect of acute phase reaction (APR). Haptoglobin (Hp) and alpha 2
      macroglobulin (alpha 2-M) are among the most important APP in rats. In this study
      AO (Albino Oxford) and DA (Dark Augustin) inbred strains of rats, with different
      resistance to trauma, were used to compare concentrations of Hp, alpha 2-M, IL-1,
      IL-6 and TNF, before and after tourniquet trauma. Cytokines IL-1, IL-6 and TNF
      have an important role in APP gene expression. Our results showed that before
      trauma, more resistant AO rats had higher concentrations of Hp and alpha 2-M
      compared to DA rats. The influence of genetic elements of these differences is
      significant. Tourniquet trauma caused an early increase of IL-1, IL-6 and TNF
      activities in the serum which preceded the increase in the Hp and alpha 2-M
      concentrations but differences between strains were not found.

PMID- 11521462
TI  - [Hemotherapy in kidney transplantation].
AB  - A total of 40 kidney transplantations (37 males and 3 females) from living donors
      (Group I) and 10 kidney transplantations (6 males and 4 females) from cadavers
      (Group II) were performed in the period 1996-October 1999 at the Military Medical
      Academy (MMA). Lymphocytotoxic crossmatching was done before each kidney
      transplantation and results from all tests were negative for all recipients. All
      donors had the same blood group in ABO system as the recipients. In perioperative
      transfusion treatment (hemotherapy) determined quantity of filtered red blood
      cells (F-RBCs) and/or filtered platelets (F-PLT) were given to recipients
      according to intraoperative blood loss and their clinical state. Leukoreduction
      filters were used to prevent HLA alloimmunization. In only 4 (8%) recipients in
      group I transfusion therapy was not applied perioperatively. An average of 3.27
      units of F-RBCs (929.44 mL) was used intraoperatively in 36 (72%) recipients in
      group I, an average of 1.9 units of F-RBCs (521 mL) was used before kidney
      transplantation in 10 (20%) recipients in group I and an average of 2.65 units of
      F-RBCs (739.23 mL) was used postoperatively in 26 (52%) recipients. In all
      recipients from group II transfusion therapy was applied perioperatively. An
      average of 3.4 units of F-RBCs (953 mL) was used intraoperatively. An average of
      4.9 units (1.328 mL) and an average of 1.4 units of F-PLT were used
      postoperatively. All recipients well tolerated the therapy and no adverse effects
      of the therapy were observed. The need for transfusion therapy intraoperatively
      was approximatively same in both recipient groups, while in recipients from
      cadavers need for transfusion support in posttransplantation period was much
      higher.

PMID- 11521463
TI  - [Defense mechanisms in soldiers during the period of adaptation to the military
      environment].
AB  - An important role during the adaptation period to the military service in the
      first three months have the defense mechanisms, which belong to the adaptive
      functioning of an organism. The aim of this study was to determine the defense
      mechanisms of soldiers in adaptation to the military environment. The sample
      consisted of 144 adapted (group A) and 400 nonadapted (group NA) soldiers. The
      applied instruments were: Social-demographic questionnaire and DSQ-40 (Defense
      Style Questionnaire--short form). The results of this study show that soldiers of
      NA group use immature defense mechanisms and soldiers of group A use mature
      defense mechanisms. A significant correlation existed between soldiers of groups
      A and NA in the use of: mature defense style (p < 0.01), humor (p < 0.005) and
      sublimation (p < 0.001). It was concluded that there was a relationship between
      maturity of defense mechanisms and level of adaptation to the military service
      and factors of the family environment.

PMID- 11521464
TI  - [Neurologic manifestations after surgical interventions].
AB  - Administration of general anesthesia is rarely accompanied with newly developed
      postoperative neurological complications. We analyzed postoperative complications
      after general anesthesia where an urgent neurologic assistance was necessary. The
      investigation included 120 patients. The same neurologist performed neurologic
      examination and electroencephalography, and computerized tomography (CT) was
      performed if necessary. In 96 (80%) patients focal stimulative or destructive
      phenomena such as epi-seizures or neurologic deficit were not detected by
      neurologic examination. In 9 (7.5%) patients were detected consciousness crisis.
      In 6 patients (5%) were registered right extremities weakness with motor
      dysphasia, which was withdrawn in first 24 hours. In these cases EEG revealed
      weak activity in theta frequency, above frontoparietal regions, bilaterally. In 6
      (5%) patients was registered neurologic deficit of hemiparesis or semi-severe
      degree with development of ischemic lesion confirmed by CT. In 6 (5%) patients,
      CT scan revealed the presence of mild brain edema. Also, positive correlation
      between duration of anesthesia, age and metabolic disorders, specially diabetes
      mellitus, was found. We concluded that age, type of surgical intervention and
      duration of general anesthesia had the greatest influence on the development of
      neurologic disorders during and after general anesthesia, and the presence of
      metabolic disorders and previous brain damage increase the risk for the onset of
      these complications.

PMID- 11521465
TI  - [Echocardiographic evaluation of left ventricular diastolic function in patients
      with aortic valve stenosis].
AB  - Impairment of left ventricular diastolic function in aortic valve stenosis occurs
      very early and precedes the impairment of systolic function. Aim was to examine
      left ventricular diastolic function and its association with severity of
      myocardial hypertrophy and clinical picture. The paper comprised 78 patients with
      isolated aortic valve stenosis in whom were performed ultrasonography and
      catheterization. No significant differences in parameters of diastolic filling
      were observed in patients with mild hypertrophy and preserved systolic function
      compared to healthy subjects. In patients with moderate myocardial hypertrophy,
      left ventricular filling was decreased in an early diastole (Emax 51 +/- 5 cm/s,
      Evti 6.4 +/- 1.1 cm) and increased in late diastole (Amax 88 +/- 11 cm/s, Avti
      11.4 +/- 1.8 cm), while deceleration time was prolonged (DT 171 +/- 32 ms).
      Pulmonary vein flow was decreased during diastole (Dmax 33 +/- 5 cm/s, Dvti 7.6
      +/- 2 cm). Pseudonormalization of flow through mitral valve was observed in
      patients with pronounced hypertrophy of left ventricular wall (mass > 180 g/m2):
      increase of the velocity during the phase of fast left ventricular filling (Emax
      72 +/- 13 cm/s, Evti 9.8 +/- 2.1 cm), decrease during atrial contraction (Amax 31
      +/- 6 cm/s, Avti 3.7 +/- 0.4 cm), reduction in deceleration time (DT 116 +/- 11
      ms), while pulmonary vein flow velocity was increased during the early diastole
      (Dmax 64 +/- 17 cm/s, Dvti 10.7 +/- 2.2 cm). Likewise, significant correlation
      between clinical picture and type of blood flow through mitral valve was
      observed.

PMID- 11521466
TI  - [Results of medical selection of drivers and candidates for drivers of motor
      vehicles].
AB  - The aim of this study is the analysis of medical selection of drivers and
      candidates for car drivers. The examination included 41,561 drivers (36,008
      candidates for car drivers sent to preliminary medical examination, 5,175
      professional drivers sent to periodic medical examination and 378 drivers sent to
      special medical examination). At the preliminary medical examination, 1.5% of
      candidates for car drivers were declared to be incapable of driving and 8.4% of
      candidates had a limited driving ability. At the periodic medical examination,
      8.2% of drivers were declared to be incapable to driving and 26% of drivers had a
      limited driving ability. At the special medical examination, 34.9% of drivers
      were declared to be incapable for driving and 54.3% of drivers had a limited
      driving ability. The reasons for driving incapability and for limited driving
      ability were the disturbances of psychologic-psychiatric and neurologic state,
      cardiovascular diseases, endocrine diseases and sight disturbances. In our
      opinion, medical selection of drivers and candidates for car drivers is a
      significant preventive measure of traffic trauma. New, more subtle methods for
      determination of the latent disturbances must be developed. Periodic medical
      examination for amateurs in the period between the preliminary medical
      examination and 65 years of age must biobligatory.

PMID- 11521467
TI  - [Formulation of calcium acetate tablets].
AB  - The results of the testing of calcium acetate tablets, produced by direct
      compression and by wet granulation (Ph. Jug. IV) are presented. Tablet hardness,
      friability and disintegration were determined. The best properties were observed
      in the tablets produced with maize starch. This procedure is fast and simple, and
      compound tablets of calcium acetate fulfill the current requirements for this
      type of preparation.

PMID- 11521468
TI  - [Surgical treatment of Parkinson disease].

PMID- 11521470
TI  - [Clinical manifestations of the antiphospholipid syndrome].

PMID- 11521469
TI  - [Levels of patient irradiation in the radiodiagnostic use of ionizing irradiation
      in Serbia].

PMID- 11521471
TI  - [Erythrocyte concentrates and their substitutes in the treatment of patients with
      hypovolemia].

PMID- 11521472
TI  - [Crimean-Congo hemorrhagic fever].
AB  - Crimean-Congo hemorrhagic fever was for the first time recognized in Yugoslavia
      in 1971. In this paper were presented clinical and laboratory findings of a
      patient infected with Crimean-Congo hemorrhagic fever in Kosovo in 1999. The
      disease was manifested with fever, headache, vomiting, myalgia, abdominal pain,
      pharyngitis, conjuctival injection, diarrhoea, hypotension, gingival bleeding,
      skin hemorrhages, hematuria, hepatomegaly, splenomegaly, jaundice,
      thrombocytopenia, prolonged prothrombin and partial thromboplastin time, high
      serum fibrinogen degradation product, leukocytosis, mild anemia, elevated levels
      of bilirubin and serum aminotransferases. Diagnosis was set clinically,
      epidemiologically and supported by serological tests. Supportive management of
      hypotension, multi-organ failure, coagulation disturbances the patient was of the
      utmost in the treatment together with the isolation and prophylactic measures.

PMID- 11521473
TI  - [Tuberous sclerosis].
AB  - Tuberous sclerosis is a rare hereditary disease which appears immediately after
      birth of during the second and third year of life. It is a multiorgan disorder
      characterized by convulsions, mental retardation and focal angiofibromyoma. The
      main findings are brain lesions including tuberous and astrocytes hamarthomas by
      which this disease was named. Renal alterations are angiofibromyolipoma and
      cysts, which are present in 40-80% of patients. The diagnosis is based on
      clinical, radiological and histological findings. This disease has a progressive
      course and fatal outcome. The therapy is symptomatic and surgical. The aim of
      this paper was to present this rare disease, which occurred in this patient
      during fourth year of life. Besides brain changes the patient also has extensive
      morphological renal alterations and renal failure. She died in 40th year of life
      due to multiorgan dysfunction.

PMID- 11521475
TI  - Watch it! Attorneys general become more active as healthcare finances grab public
      eye.

PMID- 11521474
TI  - [Onychatrophy in a female patient with lichen planus].
AB  - A case of female patient with onychatrophy, as a single clinical manifestation of
      lichen planus is reported. Nail histopathologic and direct immunofluorescent
      findings confirmed the diagnosis.

PMID- 11521476
TI  - Christus shows market hunger.

PMID- 11521477
TI  - How much is too flexible? Critics say HHS decision to give states leeway may not
      reduce uninsured.

PMID- 11521478
TI  - Texas prosecutor probes free care.

PMID- 11521479
TI  - Showing them the way. Feds settle Mo. abortion-referral controversy that
      jeopardized clinic funding.

PMID- 11521480
TI  - Into the frying pan? Hospitals wary of plan to reform Medicare's contracting
      rules.
AB  - Hospital executives have plenty of horror stories to share when the topic is
      their Medicare fiscal intermediaries. In fact, some facilities have lost millions
      because of errors by these private contractors. Nevertheless, hospitals remain
      wary of change. "Sometimes the devil you know is better than the one you don't,"
      one billing consultant says.

PMID- 11521481
TI  - 2001 physician compensation report. Unequal opportunities. Anesthesiologists,
      radiologists lead the pay parade, while generalists lag behind.

PMID- 11521482
TI  - Buying trouble. Acquisition of struggling hospitals helps Sutter Health build
      market share.

PMID- 11521483
TI  - Nice try. Scully denies New York hospital's bid for higher Medicare rates.

PMID- 11521484
TI  - JCAHO database role worries AHA.

PMID- 11521485
TI  - AAHP in the lead. Exec, insurers defect from rival HIAA.

PMID- 11521487
TI  - Liability insurance for a physician assistant.

PMID- 11521486
TI  - Managed care on trial.

PMID- 11521488
TI  - Get the most out of modifiers.

PMID- 11521489
TI  - Financial survey. Women gain ground.

PMID- 11521490
TI  - The new IOM report: will it change your practice?

PMID- 11521491
TI  - The needlestick we fear the most.

PMID- 11521492
TI  - Doctors who go the extra mile. Tadeusz J. Majchrzak. Patients wonder when he
      sleeps.

PMID- 11521494
TI  - America's best medical society?

PMID- 11521493
TI  - Keep that insurer from blocking your disability claim.

PMID- 11521495
TI  - Hospital-stay guidelines: just plain weird.

PMID- 11521496
TI  - Indoor air and the public good.

PMID- 11521497
TI  - Chlorinated ethyl and isopropyl phosphoric acid triesters in the indoor
      environment--an inter-laboratory exposure study.
AB  - The chlorinated organo-phosphate triesters, tris(2-chloroethyl)-phosphate (TCEP)
      and tris(monochloroisopropyl)-phosphate (TCPP), are employed in consumer articles
      for indoor usage, e.g. flame retardants and plasticizers in foam material as well
      as in paints, varnishes and wallpapers. As a result of this widespread usage,
      employing domestic dust as a matrix, both chemicals have been detected in the
      indoor environment. TCEP was present in 85% of a total of 983 samples, whereas
      TCPP was found in 60-90% of 436 cases (with levels ranging from 0.1 to 375
      mg/kg). Since TCEP and TCPP residues in domestic dust are assumed to be
      condensates arising from primary sources, spot check analysis of various indoor
      materials was performed. The results show that soft foams, paints and wallpapers
      contained mainly TCEP, whereas in insulation and sealant foams high levels of
      TCPP were found. Moreover, TCEP can also be detected in indoor air in
      concentrations up to 6,000 ng/m3. On the basis of this data, we estimated the
      levels of indoor exposure via oral and inhalative ingestion.

PMID- 11521498
TI  - Phthalic esters in the indoor environment--test chamber studies on PVC-coated
      wallcoverings.
AB  - Phthalic acid esters are important additives in polyvinyl chloride (PVC)
      products. Since PVC plastisoles for the production of wallcoverings contain about
      30% phthalic acid esters, it is a crucial question whether these products can
      contribute to the pollution of the indoor environment. In this study, the
      emission of several technically relevant phthalates from PVC-coated wallcoverings
      were measured in emission test chambers under standard room conditions. During a
      14-day test period, both the chamber air concentrations and the condensation on a
      cooled plate (fogging) were determined. In the chamber air, maximum
      concentrations of 5.1 micrograms/m3 for di-n-butylphthalate (DBP), 2.08
      micrograms/m3 for di-pentylphthalate (DPP) and 0.94 microgram/m3 for di-(2
      ethylhexyl)phthalate (DEHP) were found. After 14 days of exposure, up to 60.4
      micrograms DEHP and 17.7 micrograms DPP could be quantified on the cooled plates
      of the fogging apparatus. The amounts of DBP and DIBP were significantly lower. A
      simple exposure calculation indicated no specific risk of an increased phthalate
      exposure in rooms with PVC wallcoverings.

PMID- 11521500
TI  - Influence of local airflow on the pollutant emission from indoor building
      surfaces.
AB  - This article reports the results of an investigation, based on fundamental fluid
      dynamics and mass transfer theory, carried out to obtain a general understanding
      of the mechanisms involved in the emissions from building materials in ventilated
      rooms. In addition, a generally applicable method for the prediction of surface
      emissions is proposed. The work focused on the emission of vapours and gases and
      no particulate emissions were considered. The methods used were numerical
      calculations by computational fluid dynamics (CFD) and full-scale laboratory
      experiments. It was found that the emissions are a strong function of air-change
      rate, local air velocity and local turbulence, as the mass transfer coefficient
      increases in proportion to these parameters. The findings further show that the
      mass transfer coefficient increases in proportion to the velocity when the
      emission is controlled by evaporation from the surface. With regard to diffusion
      controlled emissions, the mass transfer coefficient is unaffected by the
      velocity.

PMID- 11521499
TI  - Nitrous acid interference with passive NO2 measurement methods and the impact on
      indoor NO2 data.
AB  - Recent research has demonstrated that nitrous acid (HONO) is produced in indoor
      environments by NO2 reacting with interior surfaces, and is also emitted directly
      by some combustion sources. We have recently characterized the interference by
      HONO to NO2 measurements made by several commonly used continuous NO2 monitors.
      This paper reports on the effect of HONO on NO2 measurements made by passive
      sampling devices. The objective of this study was to evaluate this interference,
      and the accuracy and precision of passive samplers used for indoor NO2
      measurements. We report that HONO interferes quantitatively with three of the
      four NO2 passive samplers tested.

PMID- 11521501
TI  - Fungal extracellular polysaccharides, beta (1-->3)-glucans and culturable fungi
      in repeated sampling of house dust.
AB  - Fungal exposure inside homes has been associated with adverse respiratory
      symptoms in children and adults. While fungal assessment has traditionally relied
      upon questionnaires, fungal growth on culture plates and spore counts, new
      immunoassays for extracellular polysaccharides (EPS) and beta (1-->3)-glucans
      have enabled quantitation of fungal agents in house dust in a more timely and
      cost-effective manner, possibly providing a better measure of fungal exposure. We
      investigated associations among measurements of EPS, beta (1-->3)-glucans and
      culturable fungi obtained from 23 Dutch homes. From each home, dust samples were
      vacuumed from the living room floor twice during the Fall, Winter and Spring
      seasons for a total of six collections (every 6 weeks from October 1997 to May
      1998). Samples were sieved and fine dust was analyzed for EPS from Aspergillus
      and Penicillium spp. combined, beta (1-->3)-glucans and culturable fungi. EPS was
      positively associated with glucan; an increase from the 25th to the 75th
      percentile of glucan concentration was associated with a 1.6-fold increase in EPS
      concentration (95% CI = 1.3 to 2.0; p < 0.01). The most significant variables
      associated with EPS and glucan concentrations were the surface type that was
      vacuumed and the concentration of total culturable fungi (in colony forming units
      (CFU)/g dust), with an increase in CFU/g from the 25th to the 75th percentile
      associated with a 1.3 (1.1-1.6)-fold increase in glucan and a 1.7 (1.3-2.2)-fold
      increase in EPS concentrations. In addition, the within-home variation of EPS
      levels were smaller than those between homes (25,646 U/g vs. 50,635 U/g), whereas
      the variation of glucan levels was similar within and between homes (1,300 vs.
      1,205 micrograms/g). These positive associations suggest that house dust
      concentrations of beta (1-->3)-glucan, and particularly those of EPS, are good
      markers for the overall levels of fungal concentrations in floor dust which is a
      surrogate for estimating airborne fungal exposure.

PMID- 11521502
TI  - Differences in inflammatory responses and cytotoxicity in RAW264.7 macrophages
      induced by Streptomyces Anulatus grown on different building materials.
AB  - Streptomyces anulatus, an indicator microbe of mold in buildings, was grown on
      different building materials in order to study the impact of growth conditions on
      the ability of the spores of this microbe to induce toxicity and inflammatory
      responses. The microbes were grown for 2 months on sterilized and unsterilized
      wood, chipboard, concrete, plaster board and mineral wool in tight glass vessels
      under humid conditions. The highest microbial spore concentration was detected on
      the sterilized mineral wool followed by the sterilized plaster board and the
      unsterilized mineral wool. Mouse RAW264.7 macrophages were exposed in vitro for
      24 h to the spores of S. anulatus and the production of the inflammatory
      mediators, nitric oxide (NO), tumor necrosis factor alpha (TNF alpha),
      interleukin-6 (IL-6), interleukin-10 (IL-10) and cytotoxicity, were measured. The
      dose equivalent to 5 x 10(5) spores/ml of medium was used to compare the
      different materials. The most intense production of NO (11.6 microM), TNF alpha
      (560 pg/ml) and IL-6 (2800 pg/ml) in macrophages was induced by the spores grown
      on sterilized plaster board. They also caused the greatest loss of cell viability
      (39%). The spores grown on sterilized concrete induced significant production of
      NO (1.5 microM) and decreased cell viability (22%), and the spores grown on
      unsterilized and sterilized mineral wool increased production of NO (4.1 microM
      and 0.8 microM, respectively). The spores did not stimulate production of the
      anti-inflammatory cytokine IL-10. These results indicate that the ability of S.
      anulatus to induce inflammatory responses and cytotoxicity in macrophages is
      dependent on the growth conditions provided by different building materials.

PMID- 11521503
TI  - Investigating sources of response variability and neural mediation in human nasal
      irritation.
AB  - A major component of indoor air complaints is nasal irritation (NI), yet there is
      an extreme paucity of quantitative concentration-response data from normosmics
      (individuals who report normal odor sensation). Due to an assumption that NI is
      mediated solely by the activation of the trigeminal (fifth cranial) nerve, much
      of the small amount of available information has been obtained from anosmic
      individuals, who lack olfactory (first cranial) nerve input to the brain and,
      thus, only have nasal trigeminal input remaining. In a repeated measurements
      design, the NI responses of 31 normosmic and four anosmic individuals were
      quantified in response to a range of concentrations of propionic acid generated
      by an automated air-dilution olfactometer. A variance analysis approach was used
      to apportion different nested sources of variation (within-session, within
      individual, inter-individual) in NI responses. In contrast to anosmic NI and
      normosmic odor performance, NI response by normosmics exhibited considerable
      variation at all three levels. However, this variation did not obscure the
      observation that, in agreement with electrocortical measurements by Hummel et al.
      (1996), NI sensitivity in normosmics clearly exceeded that of anosmics. These
      observations provide support for enhanced research efforts to better understand
      the neural basis of NI so that its occurrence in actual environments may be
      effectively minimized.

PMID- 11521504
TI  - Comparison of two-level and three-level classifications of moisture-damaged
      dwellings in relation to health effects.
AB  - A total of 630 randomly selected dwellings were surveyed for visible signs of
      moisture damage by civil engineers, and questionnaire responses were collected
      from the occupants (a total of 1,017 adults) to analyse the association between
      moisture damage and occupant health. A three-level grading system was developed,
      which took into account the number of damage sites in buildings and estimated the
      severity of the damage. In the present study, this grading system was tested as
      an improved model of moisture damage-related exposure in comparison to a
      conventional two-category system: based on independent, technical criteria it
      also allowed dose-response to be estimated. The questionnaire probed 28
      individual health symptoms, based on earlier reported associations with building
      moisture and mould-related exposure. Criteria in evaluating the goodness of the
      selected exposure model were (1) dose-responsiveness and (2) higher risk compared
      to a two-level classification. Dose-responsiveness was observed with the three
      level classification in 7, higher risk in 10, and both criteria in 5 out of 28
      health symptoms. Two-level classification had higher risk in 4 health symptoms.
      Dose-dependent risk increases for respiratory infections and lower respiratory
      symptoms, and recurrent irritative and skin symptoms were observed with the three
      level classification using symptom score variables. Although the results did not
      unambiguously support the three-level model, they underline the importance of
      developing more accurate exposure models in assessing the severity of moisture
      damage.

PMID- 11521505
TI  - Low relative humidity and aircraft cabin air quality.
AB  - Mucosal irritation remains a common complaint among travelers and flight
      attendants in aircraft cabins. Despite the fact that very low humidity is
      routinely encountered, few studies of its effects have been conducted in the
      cabin environment. The authors reviewed chamber and field studies in the
      experimental literature to explore whether there is an association and, if so, at
      what level it was likely to be present. Subjects who participated in prior
      research were not always able to perceive low humidity or changes in the humidity
      level and, at times, this inability has been confused in the literature with the
      lack of a humidity effect. The studies with more powerful experimental designs
      have demonstrated the effects of low humidity, such as drying of the skin and
      mucus membranes, and that a modest increase in relative humidity seems to
      alleviate a great number of symptoms. The exposure duration below during which
      the effects of low humidity are not noticeable is in the order of 3 to 4 h. It is
      conceivable that some symptoms experienced by flight attendants and passengers,
      especially on flights lasting 3 h or longer, may stem from low humidity.

PMID- 11521506
TI  - Identification of a human LNX protein containing multiple PDZ domains.
AB  - Recently PDZ domains have been recognized as crucial organizers of protein
      complexes at the plasma membrane. Here we report the cloning of a novel 3.7-kb
      cDNA LNX from a human fetal brain cDNA library. The deduced amino acid sequence
      shares about 88% identity with the p70 form of Lnx, which is the mouse ligand of
      Numb protein X. Motif analysis reveals five protein-interaction modules
      conservative to those in the Lnx protein, including four PDZ domains and a NPXY
      motif for binding of the Numb PTB domain. Northern blot analysis shows that the
      length of the transcript in brain is distinct from those in other tissues. By
      radiation hybrid mapping, we localize the LNX gene to human chromosome 4q12
      between marker D4S1577 and marker D4S1594. We predict that LNX may be important
      for the organization of signaling complexes in Numb-involved pathways or pathways
      regulated by other PTB-containing proteins.

PMID- 11521507
TI  - Male hybrid sterility of mice with the genomic region of the KitW mutation and
      the KitS allele from Mus spretus.
AB  - Two congenic strains, C57BL-KitW and C57BL-KitS, were generated. The KitW allele
      originated from strain WB-KitW and the KitS allele from Mus spretus. The
      KitW/KitS males showed hybrid sterility with small testes, but the females were
      fertile. The development of the seminiferous tubules of KitW/KitS males stopped
      before the spermatocyte stage and they were almost free of sperm. The Kit gene is
      located at position 42 on chromosome 5. We investigated in the C57BL-KitS
      congenic strain which part of the chromosomal region adjacent to the KitS allele
      is introduced from SPR into a C57BL background. The region between positions 42
      and 44 was derived from SPR. Eleven amino acid substitutions of the KitS cDNA
      were detected by comparison with the sequence data of the +Kit cDNA from C57BL;
      seven were in the extracellular domain, one in the transmembrane domain, two in
      the kinase I domain, and one in the carboxy-terminal tail. The Kit mRNA derived
      from both KitW and KitS alleles was expressed in the sterile testes of KitW/KitS
      males.

PMID- 11521508
TI  - Loss of expression of alcohol dehydrogenase in adult males of Drosophila pachea.

PMID- 11521510
TI  - Genetic structure and heterozygosity variation between generations of Ophiopogon
      xylorrhizus (Liliaceae s.l.), an endemic species in Yunnan, southwest China.

PMID- 11521509
TI  - Effect of ionic concentration on the higher-order structure of prophenol oxidase
      in Drosophila melanogaster.
AB  - Phenol oxidase in Drosophila melanogaster occurs as precursors designated
      prophenol oxidases A1 and A3. Crossing experiments between isozyme variants
      proved that prophenol oxidase in this species is a homodimer. Prophenol oxidases
      were partially purified using ammonium sulfate fractionation, phenyl Sepharose,
      and DEAE-cellulose column chromatography. The preparations were mixed, then
      dialyzed against buffer containing varying salt concentrations. The resulting
      prophenol oxidase was analyzed by gel electrophoresis. At 20 mM KCl or NaCl, two
      bands of phenol oxidase were observed, corresponding to the parental ones as
      monomer, whereas at 200 mM KCl or NaCl, three bands appeared in the gel, one
      being a dimer. The monomer-dimer reversibility of the Drosophila prophenol
      oxidase depends on the salt concentrations. The phenol oxidase activity remained
      unaffected within the KCl concentrations tested. Considering the ionic
      concentration of Drosophila hemolymph, these results indicate that prophenol
      oxidase exists as a dimer in vivo, and the higher-order structure of prophenol
      oxidase can be altered reversibly by ionic concentrations in vitro.

PMID- 11521511
TI  - Male accessory gland secretory proteins in a few members of the Drosophila nasuta
      subgroup.
AB  - Male accessory gland secretory proteins in seven members of the Drosophila nasuta
      subgroup have been analyzed by SDS-PAGE. The study revealed remarkable simplicity
      in the patterns. The protein fractions, which migrate in three groups, could be
      categorized as "major" and "minor." The number of major fractions varies from a
      maximum of eight to a minimum of four. Group I consists of high molecular weight
      fractions, and group III, low molecular weight fractions. Among different members
      analyzed, the variation with respect to pattern and the number of fractions are
      confined largely to group III protein fractions, while group I and II fractions
      are found to be conserved to a greater extent. These proteins are PAS positive
      and group III fractions are not sensitive to silver staining. Analysis of these
      tissue specific proteins in the F1 and F2 of interspecific crosses and backcross
      progeny as well as volume analysis revealed that a 26-kD fraction in D. n. nasuta
      follows an autosomal pattern of inheritance, while a 55-kD and a 25-kD fraction
      in D. n. albomicans and a 24-kD fraction in D. n. kepulauana follow an X-linked
      pattern of inheritance.

PMID- 11521512
TI  - [Therapeutic efficacy of a topical tolnaftate preparation in guinea pig model of
      tinea pedis].
AB  - The therapeutic efficacy of a topical antifungal ointment containing 2%
      tolnaftate was studied in a guinea pig model of tinea pedis using the following
      four topical antifungal preparations commercially available as reference drugs:
      variotin (3,000 U/g ointment); phenyl-11-iodo-10-undecynoate (0.5% ointment);
      siccanin (1% ointment); and clotrimazole (1% cream). After the infection fully
      developed, the infected animals were treated twice daily with the testing drug or
      reference drug for consecutive four weeks. Therapeutic efficacy was mainly
      evaluated on the basis of the extent of the yield of fungal cultures from the
      infected skin tissues (infection intensity) at the end of the treatment period.
      In animal groups treated with tolnaftate as well as with three reference drugs,
      siccanin, phenyl-11-iodo-10-undecynoate and clotrimazole, the average infection
      intensity was significantly lower than that for untreated control group (P < 0.05
      0.005) although no culture-negative animal was seen in any treated animal group.
      Comparing with all the reference drugs, tolnaftate was the most highly effective
      and there was significant difference in the average infection intensity between a
      tolnaftate treated and each reference drug-treated groups (P < 0.01-0.005). These
      results confirm the clinical usefulness of the current tolnaftate preparation in
      the treatment of patients with tinea pedis and probably other clinical forms of
      dermatophytoses.

PMID- 11521513
TI  - [Effects of different variants of low-protein diet on progression of chronic
      renal failure and indices of nutritional status in predialysis stage].
AB  - AIM: To investigate effects of different variants of low-protein diet (LPD)
      (standard and with soy bean protein isolates) on inhibition of chronic renal
      failure (CRF) progression and prevention of protein-energy insufficiency in
      predialysis patients. MATERIALS AND METHODS: 150 patients with CRF were divided
      into three groups 50 patients each. Group 1 patients were given combined LPD with
      addition of soy bean isolate (0.4 g of protein per 1 kg of recommended body mass
      a day with standard diet and 0.2 g/kg with protein isolate SUPRO 760). Group 2
      patients were given standard LPD without additives (0.6 g/kg a day). Patients of
      group 3 received free diet. All the patients were normally supplied with energy
      (at least 30-35 kcal/day). In the course of 26 months, clinical, laboratory,
      anthropometric, expected and functional parameters were measured each 4 months.
      RESULTS: Progression of CRF inhibited in patients with restricted protein
      provision. LPD had no negative effect on laboratory indices. Soy bean isolate LPD
      was more effective in inhibition of the disease progression than the standard
      one. CONCLUSION: LPD can be used for a long time for inhibition of the
      progression of CRF provided energy requirements are met. LPD with food additives
      (soya bean protein isolates) hold perspective for correction of metabolic
      disorders.

PMID- 11521514
TI  - [Course of heart failure in patients with terminal chronic kidney failure on
      chronic hemodialysis].
AB  - AIM: To evaluate peculiarities of the course of cardiac failure (CF) in
      initiation of hemodialysis therapy (HT) in patients with terminal chronic renal
      failure (CRF) and 24 months after HT; to elucidate CF causes late in HT. MATERIAL
      AND METHODS: Cardiohemodynamics was studied in 152 patients with terminal CRF
      during 2 years of HT. RESULTS: At initiation of HT, cardiohemodynamics was
      characterized by hyperkinetic syndrome, high total peripheral resistance, weak
      left ventricular systolic function, diastolic dysfunction. Chronic HT for 2 years
      led to attenuation of hyperkinetic syndrome, improvement of left ventricular
      systolic function, highly increased bypass blood flow along the arteriovenous
      fistula. The correction of the blood flow along the arteriovenous fistula
      arrested manifestations of CF in all the patients. CONCLUSION: Drugs with
      positive inotropic action are contraindicated in patients with terminal CRF on
      chronic hemodialysis having CF. Regular measurements of blood flow along the
      arteriovenous fistula are recommended for early detection and correction of
      increased bypass blood flow.

PMID- 11521515
TI  - [Effects of acute pharmacological blockade of the renin-angiotensin system on
      intrarenal hemodynamics in patients with systemic lupus erythematosus and
      systemic scleroderma].
AB  - AIM: To evaluate effects of an ACE inhibitor captopril on intrarenal hemodynamics
      during acute test in patients with lupus nephritis (LN) and chronic sclerodermic
      nephropathy (CSN). MATERIAL AND METHODS: Renal hemodynamics was studied using
      ultrasound duplex scanning of renal vessels (UDS) on Vingmed SD-100 unit in 5
      patients with SLE with renal affection, 5 patients with scleroderma systematica
      (SS) with renal affection. The hemodynamic parameters were measured before and 1
      hour after administration of 50 mg captopril. RESULTS: LN were found to have low
      arterial perfusion. CSN patients exhibited low intrarenal blood flow in high
      resistance of small vessels. Captopril improved intrarenal hemodynamics
      (enhancement of linear and volume blood flow) in LN patients; in CSN renal artery
      dilated and resistance of small vessels reduced while renal arterial perfusion
      increased. CONCLUSION: Improvement of intrarenal hemodynamics in LN and CSN
      patients in response to captopril allows to recommend administration of ACE
      inhibitors in SLE and SS with renal damage. Ultrasonic duplex scanning of renal
      vessels provides detailed information about the condition of intrarenal vessels
      without invasion.

PMID- 11521516
TI  - [Kidney damage in primary antiphospholipid syndrome].
AB  - AIM: To characterize clinical manifestations, course and laboratory signs of
      nephropathy in primary antiphospholipid syndrome (PAS). MATERIAL AND METHODS: 6
      patients with PAS and renal affection were observed for 10 years since 1991. They
      were examined for anticardiolipin antibodies and/or lupus anticoagulant. Renal
      tissue was studied morphologically in one patient. RESULTS: In all the patients
      renal damage manifested with arterial hypertension associated with isolated
      proteinuria. The majority of the patients had renal dysfunction. All of them had
      elevated level of antibodies to cardiolipin primarily in combination with lupus
      anticoagulant. Histological changes of renal tissue presented with thrombotic
      microangiopathy of glomerular and extraglomerular vessels, intimal proliferation
      and vascular wall thickening with occlusion of their lumen which combined with
      morphological indicators of focal segmental glomerulosclerosis. CONCLUSION: The
      thrombotic process in the intrarenal vessels in PAS dictates the necessity to
      develop novel approaches to treatment of such patients. In addition to
      immunodepressants the treatment should include indirect anticoagulants and
      antiaggregants.

PMID- 11521517
TI  - [Relationship between mass of the left ventricular myocardium and uric acid
      metabolic imbalance in patients with arterial hypertension].
AB  - AIM: To analyse relationships between left ventricular myocardium mass (LVMM) and
      imbalance of uric acid metabolism in patients with arterial hypertension (AH).
      MATERIAL AND METHODS: Body mass index, waist/hip circumference index, levels of
      uric acid in the blood and urine, urinary excretion of albumin, LVMM were
      estimated in 106 patients with mild and moderate AH (70 males and 36 females,
      mean age 51 +/- 8.5 years). RESULTS: Hypertensive patients with and without
      metabolic imbalance of uric acid differ significantly by LVMM index. The latter
      was higher in metabolic imbalance of uric acid, being the highest if this
      imbalance combined with microalbuminuria. CONCLUSION: Imbalance of uric acid
      metabolism in AH patients may indicate affection of both the kidneys and the
      heart.

PMID- 11521518
TI  - [Urine fibrinolytic activity as an indicator of kidney damage in uric acid
      metabolic imbalance].
AB  - AIM: To determine functional fibrinolytic activity of the urine in patients with
      different forms of purine metabolism disorder. MATERIAL AND METHODS: Uricemia, 24
      h uricosuria, serum creatinine, GFR, maximal urinary specific gravity, urokinase
      activity in the urine, total fibrinolytic activity of the urine (TFAU), activity
      of plasminogen activator inhibitor (PAI) in blood were studied in 33 patients
      with genetically determined purine metabolism disorders. RESULTS: Patients with
      purine metabolism disorders vs controls had decreased TFAU and urokinase
      activity. There was no significant difference between the study and control
      groups in the levels of PAI in blood. No statistically significant difference was
      found between the patients with hyperuricemia and patients with hyperuricosuria
      in the levels of TFAU and urokinase activity, while the group with hyperuricemia
      was characterized by a decreased maximal specific urinary gravity. CONCLUSION: A
      decrease in TFAU and urokinase activity in patients with purine metabolism
      disorder was observed in the isolated hyperuricosuric stage of urite renal
      damage.

PMID- 11521520
TI  - [Role of the hemostatic system in the progression of acute glomerulonephritis].
AB  - AIM: To study basic parameters of hemostasis in the course of acute
      poststreptococcal glomerulonephritis (APSGN). MATERIAL AND METHODS: Platelets
      number and aggregation 4-platelet factor, Willebrand's factor, activated partial
      thromboplatelet time, antithrombin III, fibrin-monomeric complexes and products
      of degradation fibrinogen/fibrin were studied in 127 APSGN patients.
      Autocoagulation, prothrombin and thrombin tests were made. RESULTS: Progredient
      thrombinemia, stable elevation of Willebrand's factor, high aggregation activity
      of platelets and content of their degradation products evidence for intrarenal
      microthrombogenesis in APSGN, confirms direct involvement of platelet hemostasis
      in long-term inflammation in this disease. CONCLUSION: Mechanisms of APSGN
      development operate also through changes in hemostatic system.

PMID- 11521521
TI  - [Mesangiocapillary glomerulonephritis].

PMID- 11521519
TI  - [Effects of pathogenetic therapy on blood cholesterol in patients with
      glomerulonephritis].
AB  - AIM: To evaluate effects of corticosteroids, cytostatics, ACE inhibitors, Ang-II
      receptor blockers, HMG-CoA-reductase inhibitors on the levels of blood
      cholesterol in patients with progressive glomerulonephritis (PGN). MATERIAL AND
      METHODS: The influence of medications which are used for treatment of chronic
      glomerulonephritis on the serum levels of total cholesterol (TCh) was
      investigated in 53 patients with chronic glomerulonephritis and persistent
      nephrotic syndrome (NS). All the patients with NS or nephrotic range proteinuria
      were divided into five groups depending on the type of therapy: corticosteroids,
      cytotoxic agents, ACE inhibitors, Ang-II receptor blocker, HMG-CoA-reductase
      inhibitors. RESULTS: No negative change of serum TCh was revealed after the
      courses of treatment with corticosteroids and cytotoxic agents. Moreover,
      treatment with ACE inhibitors and Ang-II receptor blockers was accompanied with a
      significant reduction of the TCh level. CONCLUSION: ACE inhibitors and Ang-II
      receptor blockers affect some mechanisms of glomerulonephritis progression
      including hypercholesterolemia.

PMID- 11521522
TI  - [Mechanisms of biocidal action of neutrophils in patients with alcoholism and
      kidney damage of the chronic pyelonephritis type].
AB  - AIM: To study mechanisms of biocenosis action of neutrophils in alcoholics with
      chronic pyelonephritis (CP). MATERIAL AND METHODS: Functional potential of
      oxidase neutrophil system was studied in 37 males with chronic alcoholism stage
      II. 17 of them had CP. They were compared to 18 CP non-alcohol abusers
      (controls). RESULTS: CP alcoholics had lower potential of oxidase neutrophil
      system than controls and healthy subjects. CONCLUSION: Dysfunction of axygen
      dependent mechanisms of biocidic action of neutrophils in chronic alcoholics
      weakens the ability of the organism to eliminate infection and can entail defects
      in immune response.

PMID- 11521523
TI  - [Lupus nephritis in the middle of the 20th century and in the beginning of 21st
      century].

PMID- 11521524
TI  - [Heterogeneity of causes of proteinuria in patients with non-insulin dependent
      diabetes mellitus].
AB  - AIM: To make a retrospective clinicomorphological (autopsy) study of proteinuria
      causes. MATERIAL AND METHODS: The records have been analysed for 231 patients
      with non-insulin-dependent diabetes mellitus (NIDDM) over 60 years of age who
      died in a general hospital between 1990 and 1999. The choice of patients with
      diabetic nephropathy (DN) for a further morphological investigation was based on
      the presence of proteinuria (> 0.5 g/day), normal renal function. 72 patients met
      the above criteria. Of them 26 were women. RESULTS: Proteinuria occurred more
      frequently in men (63.4%). A morphological examination of the kidneys revealed
      diabetic glomerulosclerosis (diffuse and focal) in 48(67%) patients. In 24(33%)
      patients proteinuria resulted from non-diabetic affection of the kidneys:
      amyloidosis, atherosclerotic and/or hypertensive nephroangiosclerosis,
      membraneous and myelomic nephropathy, mesangioproliferative glomerulonephritis.
      Glomerular changes were not registered in 4 patients. 35(72%) DN patients had
      diabetic retinopathy which was not found in patients with non-diabetic renal
      affection. CONCLUSION: Diabetic retinopathy in patients with NIDDM and
      proteinuria allows to conclude that the latter is consequent to DN. The absence
      of diabetic retinopathy in such patients promotes a search for other causes of
      proteinuria.

PMID- 11521525
TI  - [Experience in the use of valsartan with the aim to inhibit progression of kidney
      failure in patients with chronic glomerulonephritis].
AB  - AIM: To assess the effect of valsartan, angiotensin-II receptor blocker type 1,
      on key factors of progression of chronic renal failure (CRF)--arterial
      hypertension (AH), proteinuria (PU), sodium excretion (SE)--in patients with
      chronic glomerulonephritis (CGN) and initial affection of renal function.
      MATERIAL AND METHODS: 11 patients (mean age 33.7 +/- 13.3 years, mean duration of
      nephritis 8.6 +/- 6.4 years, male to female ratio 8:3) with AH (AP > 140/90 mm
      Hg) and marked PU (> 1 g/day) who had not received immunosuppressive drugs for at
      least 6 months before the trial were given valsartan. It was administered after
      the period of "washing out" at the initial dose 80 mg/day with further addition
      of diuretics or raising the dose twice (in hyperuricemia) to decrease AP under
      140/90 mm Hg. The duration of the treatment was 3 months. RESULTS: After 3 months
      of valsartan therapy systolic arterial pressure fell from 162 +/- 18 to 138 +/-
      20 mm Hg (p < 0.05), diastolic pressure from 100 +/- 8 to 92 +/- 15 mm Hg (single
      measurements). 24-h monitoring of AP showed a significant lowering of mean 24-h
      and night systolic and diastolic AP, day-time diastolic AP, 24-h time index of
      systolic and diastolic AP. Initial antiproteinuric effect was observed after 1
      month of the treatment and after 3 months of therapy PU reduced significantly
      (from 5.7 +/- 6.0 g/day to 3.3 +/- 3.3 g/day). After 3 months sodium excretion
      significantly rose, while creatinine level and glomerular filtration rate did
      not. Potassium rose in one patient. CONCLUSION: In CGN with initial CRF valsartan
      in a dose 80-160 mg/day produces a pronounced antihypertensive and
      antiproteinuric actions, stimulates sodium excretion. No serious side effects
      were noted. It is necessary to continue studies on the ability of valsartan to
      inhibit progression of CRF.

PMID- 11521526
TI  - [Ischemic disease of the kidneys].

PMID- 11521527
TI  - [Nephro-protection: role of arterial pressure in progression of renal pathology.
      Does a nephro-protective effect depend on the choice of antihypertensive drug?].

PMID- 11521528
TI  - [Chronic aluminum intoxication in patients with terminal kidney failure on
      programmed hemodialysis (literature review)].

PMID- 11521529
TI  - [Extracorporeal therapy of rheumatoid arthritis].

PMID- 11521530
TI  - Costs and prevention of patient defection.
AB  - Although other industries have recognized that increased customer loyalty brings
      increased revenues and profitability, few medical practices have sought even to
      measure patient retention or loyalty. When patients leave a practice, new
      patients must be attracted to replace lost ones at significant cost, often
      invisible to and underestimated by physicians. Understanding the lifetime value
      of a patient may be one route that leads to better patient loyalty practices and
      enhanced profitability.

PMID- 11521531
TI  - Monitoring the pulse of your practice.

PMID- 11521532
TI  - Nonverbal aids for improving staff communication.
AB  - Speaking face-to-face is the most common form of communication between
      doctor(s)/office managers and members of the professional practice staff.
      However, several nonverbal aids can enhance understanding tremendously and may be
      used in addition to or instead of speaking. In this article, we will explore when
      and how to use the best nonverbal communication aids. These include memos, a
      staff bulletin board, an office mail center, correspondence routing, paycheck
      inserts, a staff newsletter, and staff surveys. This article also includes a
      sample staff survey and suggests situations that are not appropriate for using
      nonverbal aids.

PMID- 11521533
TI  - Office staff savvy: quality staff-patient communications as a loss prevention
      strategy.
AB  - Based on the prevalence of medical error that continues to make headlines, you
      would think that physicians are so busy defending medical malpractice lawsuits
      that they don't have time to practice medicine. Although many physicians may feel
      like this, in fact, it is not the case. Contrary to what the media would have you
      believing, it is not "the conspiracy of silence" that's keeping physicians out of
      court. It's good, old-fashioned effective communication: courtesy, empathy,
      friendliness, and professionalism. Because the complexity of health care delivery
      imposes ever-greater demands on physicians' time, medical office staff play a
      larger-than-ever role in defining the tenor of physician-patient relationships.
      It has become incumbent on staff to become the physicians' partners in
      effectuating patient relationships built on quality communications. This article
      will discuss ways in which office staff can utilize effective communications to
      improve physician-patient relationships, thereby reducing professional liability
      exposures.

PMID- 11521534
TI  - U.S. Supreme Court allows employers to require arbitration.

PMID- 11521535
TI  - Safety and compliance-related hazards in the medical practice: Part 2.

PMID- 11521537
TI  - Health care privacy: preparing for the brave new world.

PMID- 11521536
TI  - Physicians and the Americans With Disabilities Act: Part 1.

PMID- 11521538
TI  - The wireless Web and patient care.
AB  - Wireless computing, when integrated with the Web, is poised to revolutionize the
      practice and teaching of medicine. As vendors introduce wireless Web technologies
      in the medical community that have been used successfully in the business and
      consumer markets, clinicians can expect profound increases in the amount of
      patient data, as well as the ease with which those data are acquired, analyzed,
      and disseminated. The enabling technologies involved in this transformation to
      the wireless Web range from the new generation of wireless PDAs, eBooks, and
      wireless data acquisition peripherals to new wireless network protocols. The rate
      limiting step in the application of this technology in medicine is not technology
      per se but rather how quickly clinicians and their patients come to accept and
      appreciate the benefits and limitations of the application of wireless Web
      technology.

PMID- 11521539
TI  - Enterprise-wide patient monitoring improves care efficiency and lowers costs.
AB  - The Mid America Heart Institute (MAHI), located at Saint Luke's Hospital and a
      member of the Saint Luke's-Shawnee Mission Health System (SLSMHS) in Kansas City,
      Missouri, has implemented a revolutionary enterprise-wide patient monitoring
      solution via a network that connects multiple hospitals to provide real-time
      patient monitoring--a lifeline of patient data. The underlying technical
      infrastructure creates the foundation necessary to link metropolitan and rural
      facilities with instant acute care patient information. The result is an
      electronic extension of the MAHI and its proven care expertise to several
      hospitals throughout the region. This approach has yielded MAHI/SLSMHS numerous
      efficiencies, including reduced costs and standardized monitoring quality across
      the enterprise. In the process, they have garnered some unanticipated benefits:
      unique marketing exposure and a new way to build alliances with other hospitals.

PMID- 11521540
TI  - Did you remember to charge for that consult Saturday at 2 A.M.?

PMID- 11521541
TI  - Guidelines for billing liability insurance.

PMID- 11521542
TI  - Cultural difference, trust, and optimum care for minority patients.

PMID- 11521543
TI  - Variables affecting the financial viability of your practice.
AB  - Financial viability of physician practices depends upon multiple variables:
      capacity of the practice, the mix of managed care contracts, cost of care, make
      up of patient population, patient visit rates, and utilization of alternate
      methods of patient interaction. This article presents an introduction to these
      ideas; the second in this series will expand on the groundwork with a case
      scenario for a typical family practice. The articles present basic financial
      information in a practical manner, utilizing a series of worksheets to determine
      how these various items affect the bottom line.

PMID- 11521544
TI  - Delaying diabetes.

PMID- 11521545
TI  - Barry Marshall. A gutsy gulp changes medical science.

PMID- 11521546
TI  - Betty Ford. A first lady who always tells it like it is.

PMID- 11521547
TI  - Jeffrey Wigand. The insider who blew smoke at big tobacco.

PMID- 11521548
TI  - Bringing up bold babies.

PMID- 11521550
TI  - A framework for redesigning or fine-tuning your benefit package--results from a
      national survey of stressful life events.
AB  - The results of a national survey of stressful life events are introduced as a
      useful framework for redesigning or fine-tuning corporate benefit packages to
      better meet employee needs, as well as to attract and retain top talent. Among
      the specific recommendations are (a) expanded bereavement leave, (b) hospice
      services, (c) employee assistance program access, (d) child care/elder care and
      (e) group legal services. Offering benefits that enable individuals to cope more
      effectively with major life event stressors is viewed as a powerful way of
      strengthening the psychological contract between employee and employer.

PMID- 11521549
TI  - Trouble in paradise.

PMID- 11521551
TI  - Disability plans--mental condition limitations--ADA. Kimber v. Thiokol
      Corporation, Thiokol Corporation Disability Benefits plan, 196 F.2d 1092 (10th
      Cir. 1999).

PMID- 11521552
TI  - Disability insurance--ADA--benefits for mental disability, alcoholism and drug
      abuse. Weyer v. Twentieth Century Fox Film Corp., 198 F.3d 1104 (9th Cir. 2000).

PMID- 11521553
TI  - AIDS--ADA--handicap discrimination--ERISA plan--preemption. McNeil v. Time
      Insurance Company, 205 F.3d 179 (5th Cir. 2000).

PMID- 11521554
TI  - Health claim denial--standard of review--arbitrary and capricious--medically
      necessary. Carr v. The Gates Health Care Plan, 195 F.3d 292 (7th Cir. 1999),
      cert. denied, 120 S. Ct. 1675 (April 17, 2000).

PMID- 11521555
TI  - Fiduciary duty--HMOs--disclosure--physician compensation and financial
      incentives. Ehlmann v. Kaiser Foundation Health Plan of Texas, 198 F.3d 552 (5th
      Cir. 2000).

PMID- 11521556
TI  - Disclosure--severance from service--breach of fiduciary duty. Harte v. Bethlehem
      Steel Corporation, 214 F.3d 446 (3rd Cir. 2000) (opinion after rehearing).

PMID- 11521557
TI  - [Diagnostic imaging and evidence-based medicine].

PMID- 11521558
TI  - [Diagnostic imaging 2001].

PMID- 11521559
TI  - [Introduction of new preventive therapeutic principles].

PMID- 11521560
TI  - [New techniques for early diagnosis of lung cancer].

PMID- 11521561
TI  - [What can be seen by thoracic radiography--and when is additional diagnostic
      imaging necessary?].

PMID- 11521562
TI  - [Diagnostic imaging in the investigation of torture victims].

PMID- 11521563
TI  - [Diagnostic imaging in the investigation of multi-traumatized patients].

PMID- 11521564
TI  - [Selected interventional radiologic procedures].

PMID- 11521565
TI  - [New efforts in interventional radiology. Insertion and maintenance of central
      venous catheter].

PMID- 11521566
TI  - [Endovascular neuroradiological interventions].

PMID- 11521567
TI  - [Radiological classification of pituitary adenomas].
AB  - Magnetic resonance imaging (MRI) is the modality of choice in the diagnosis of
      pituitary pathology. A chronological outline and discussion of the radiological
      classifications of pituitary adenomas applied so far are presented, with a review
      in depth of the up-to-date classifications based on MRI. SIPAP is an MR
      classification used in Scandinavia. It is basically a six-figure number
      describing the extrasellar extension of the adenoma. Together with tumour size,
      it is a useful and simple method for registration of pituitary adenomas.

PMID- 11521568
TI  - [Diffusion-weighted MR imaging of the brain].

PMID- 11521569
TI  - [Proton MRS: a prognostic and diagnostic tool in the diagnosis of diffuse brain
      diseases].

PMID- 11521570
TI  - [Treatment of carotid-cavernous fistulas via endovascular approaches].
AB  - INTRODUCTION: Carotid cavernous fistulas are abnormal communications between the
      arterial system and the cavernous sinus. The patients present with pulsating
      exophthalmos, chemosis, and ophthalmoplegia. MATERIAL AND METHODS: Since 1995,
      eleven patients have been treated for carotid cavernous fistulas at Odense
      University Hospital using different endovascular approaches. Five of them were
      treated from the internal carotid artery, four with detachable balloons and one
      with Guglielmi detachable coils. Five patients were treated by venous approaches.
      In three cases, the superior ophthalmic vein was used, and in two the inferior
      petrosal sinus. One patient could not be treated. RESULTS: Ten of the eleven
      patients were treated successfully. Two of the balloons deflated in a few weeks.
      In one of the patients the carotid artery was subsequently occluded without
      problems. The other was not treated again because of age (90 years) and partial
      relief of the symptoms. In the other eight patients, the symptoms disappeared or
      were relieved. There were no complications during the procedures. The best and
      most stable results were achieved by the venous approaches. CONCLUSION:
      Endovascular treatment, especially the venous approach, should be the first
      choice in treating carotid cavernous fistulas.

PMID- 11521571
TI  - [Endovascular treatment of aortic aneurysm].

PMID- 11521572
TI  - [Endovascular treatment of uterine fibromas].
AB  - Uterine artery embolisation represents a promising new method of treating fibroid
      related menorrhagia and pelvic pain. The procedure is performed under local
      analgesia and intravenous sedation. Both uterine arteries are selectively
      catheterised under fluoroscopic control. Microparticles suspended in contrast
      medium are used to embolise the uterine vascular bed. Ischaemic pain during the
      first day is treated with intravenous morphine. Patients treated with
      embolisation can expect excellent results with respect to menorrhagia, pelvic
      pain, and reduction in the fibroid tumour volume. Women undergoing uterine
      embolisation retain their potential for future pregnancies. The procedure is well
      tolerated by patients, and possesses the advantages of shorter hospitalisation
      and recovery time, as compared to hysterectomy.

PMID- 11521573
TI  - [Use of ultrasound contrast media for the assessment of vascularization of breast
      tumors].

PMID- 11521574
TI  - [Anorectal ultrasonography].

PMID- 11521575
TI  - [Leukocyte scintigraphy: indications and diagnostic value].
AB  - Leukocyte scintigraphy is a diagnostic method that allows visualisation of
      pathological accumulation of leukocytes. Some important indications are reviewed
      with special emphasis on the diagnostic value and possible limitations. Leukocyte
      scintigraphy is valuable for diagnosing osteomyelitis in bones with a pre
      existing pathology, but probably not in chronic or vertebral osteomyelitis. The
      test is also valuable for detection of intra-abdominal abscess and vascular graft
      infection. Fever of unknown origin represents a diagnostic challenge. Although
      the sensitivity of leukocyte scintigraphy is only modest in this context, it
      seems to be a valuable addition to other tests performed in these patients.

PMID- 11521576
TI  - [Diagnostic imaging in the investigation of inflammatory bowel disease].

PMID- 11521577
TI  - [Therapeutic intervention in carotid stenosis].

PMID- 11521578
TI  - [Treatment of renovascular hypertension with percutaneous transluminal renal
      angioplasty].

PMID- 11521579
TI  - [Pulmonary arteriovenous malformations. Current therapeutic principles].
AB  - Pulmonary arteriovenous malformations are congenital vascular malformations in
      the lungs, which act as shunts so that the blood is not oxygenated or filtered.
      These patients are typically hypoxaemic with exercise intolerance and are at high
      risk of paradoxical emboli to the brain. About 25% of patients with the Rendu
      Osler-Weber syndrome (hereditary haemorrhagic telangiectasia) have these
      pulmonary malformations. A modern treatment strategy is embolisation with balloon
      or coils of the afferent arteries to the arteriovenous malformations. It is a
      minimally invasive procedure with a very high technical success and few
      complications. Embolisation prevents cerebral stroke and abscess and pulmonary
      haemorrhage and further raises the functional level. Screening for pulmonary
      arteriovenous malformations in patients at risk is recommended.

PMID- 11521580
TI  - [A snare device for removal of foreign bodies left after percutaneous
      transluminal angioplasty].

PMID- 11521581
TI  - [Treatment of recurrent epistaxis with endoscopic electrocoagulation of the
      sphenopalatine artery].
AB  - INTRODUCTION: Treatment of posterior epistaxis with an intranasal balloon
      catheter (double balloon--Epistat) or posterior balloon (Foley catheter) as a
      posterior packing combined with a gauze plug as the anterior packing is often
      very troublesome for the patient. In the western world, the introduction of
      endoscopic electrocoagulation or ligation of the sphenopalatine artery has proved
      to be effective in the treatment of persistent posterior epistaxis, and it
      reduces morbidity. We have therefore introduced the same treatment modality.
      MATERIAL AND METHODS: We have used this technique so far on six patients with
      persistent posterior epistaxis. They were admitted to the ENT Department, H:S
      Rigshospitalet, Copenhagen, during the period 1.4.2000-15.11.2000. RESULTS: The
      treatment terminated the epistaxis in all cases. One patient had anterior
      epistaxis postoperatively, and this was treated with ligation of the arterior
      ethmoidal artery. The time spent in hospital after the operation was 1-2 days.
      CONCLUSION: This method is recommended for the treatment of persistent posterior
      epistaxis, when functional endoscopic techniques are mastered. Early treatment
      reduces morbidity and cuts down the stay in hospital.

PMID- 11521582
TI  - [No effect of 33-degree hypothermia in acute traumatic brain injury].

PMID- 11521584
TI  - [On the concept of anxiety, a therapeutic model and its implications].

PMID- 11521583
TI  - [How much value can be attributed to medical documentation? Radiographic
      examination of a shoulder].

PMID- 11521585
TI  - [Medical scientific theory].

PMID- 11521586
TI  - [More on whiplash].

PMID- 11521587
TI  - [Use of angiotensin II receptor antagonists in patients with ACE inhibitor
      intolerance].

PMID- 11521588
TI  - [Significance of determination of medium weight molecules in urine in normal
      pregnancy, in complicated pregnancy and in newborns with hypoxia].
AB  - Women with normal gestation and with gestosis and diabetes and newborns exposed
      to chronic intrauterine hypoxia were examined in order to elucidate the
      diagnostic value of measuring the content of low- and medium-weight molecules
      (MWM) in the urine in some obstetrical and gynecological abnormalities. Urinary
      content of MWM was increased at late terms of pregnancy (25-40 weeks). In first
      degree nephropathy and type I diabetes without vascular complications the content
      of MWM in the urine did not change. A drop of MWM level was observed in second
      third-degree nephropathy and proteinuria, which can be attributed to impaired
      function of the kidneys. In healthy newborns no differences in MWM content were
      detected during the first day of life, but in newborns exposed to chronic
      intrauterine hypoxia MWM level was increased. Hence, measurement of MWM level in
      the urine can have prognostic significance in diseases involving gestosis and
      fetal hypoxia.

PMID- 11521589
TI  - [Detection of free histidine by thin-layer chromatography].

PMID- 11521590
TI  - [Free radical lipid peroxidation in workers of oil processing industry].
AB  - Free radical lipid peroxidation in erythrocytes, plasma, and urine was studied in
      workers engaged in oil processing industry. The examinees were divided into 3
      groups with different intensity of exposure to chemical factors: 1) 21 workers
      without contacts with chemicals; 2) 28 workers handling chemicals 2-3 times a
      weeks (risk group); 3) 46 workers permanently exposed to chemicals for 3-5 years.
      Control group consisted of 40 workers occupationally not exposed to chemicals.
      Free radical lipid peroxidation in erythrocytes, plasma, and urine was
      intensified in groups 2 and more so in group 3.

PMID- 11521591
TI  - [Magnetic resonance spectroscopy].
AB  - Life-time diagnosis of the initial pathological shifts in the organism remains an
      and still unsolved important problem of modern medicine. Magnetic resonance
      spectroscopy based on the nuclear magnetic resonance phenomenon is one of the
      methods which can help to solve this problem. Modern reports about the use of
      magnetic resonance spectroscopy in the diagnosis of various diseases are
      reviewed.

PMID- 11521592
TI  - [Erythron and renal pathology (review of literature)].

PMID- 11521593
TI  - [Evaluation of changes in erythrocyte functions and iron metabolism in patients
      with chronic renal failure treated by peritoneal dialysis].

PMID- 11521594
TI  - [Corynebacterium diphtheriae and conventional-pathogenic Corynebacteria
      (lecture)].

PMID- 11521596
TI  - [Characteristics of reversible aggregation of peripheral blood erythrocytes in
      children with acute pneumonia].
AB  - Acute pneumonia in children is associated with increase of the red blood cell
      aggregation characteristics. Pronounced changes in reversible aggregation of
      erythrocytes did not completely normalize after therapy and were the most
      pronounced in patients with complicated course of the disease, which necessitates
      intensifying the traditional methods for monitoring the efficiency of treatment
      and correction of traditional treatment protocols.

PMID- 11521595
TI  - [Universal algorithm of impairment of receptor endocytosis of saturated
      exogenous, saturated endogenous and essential polyenic fatty acids and the
      genesis of different hyperlipidemias types: facts and hypotheses].

PMID- 11521597
TI  - [The estimation of thrombocytopoiesis using automated blood analyzers].

PMID- 11521598
TI  - [Homeostasis and its correction in burn patients with gastrointestinal erosive
      ulcerative diseases].
AB  - Acute erosive ulcerative hemorrhage (EUH) is one of the most grave complications
      of burn disease, caused by impaired blood rheology, clotting, and protein status.
      Twenty-three patients with burns of 12-70% body surface were examined, 17-25% of
      burns being deep. The most pronounced changes in blood rheology and clotting with
      formation of erythrocyte aggregations, fibrin precipitation and imbalance of
      visceral proteins were observed during the shock stage (days 1-3), particularly
      pronounced in patients with acute EUH. Development of septicotoxemia favored
      secondary increase in blood clotting and rheological parameters, which led to
      thrombotic complications. The data helped improve the complex of infusion
      transfusion therapy for preventing and treating ulcerative and erosive lesions.

PMID- 11521599
TI  - [Systemic approach to clinical laboratory diagnosis of infectious endocarditis].

PMID- 11521600
TI  - [Use of bentonite clays as accumulation media for enterobacteria].
AB  - Bentonite media consisting of phosphate saline buffer and bentonite corpuscles of
      certain size are proposed as accumulation media for Enterobacteriaceae. The
      "attitude" of the studied bacteria to bentonite particles of different size is
      selective. Salmonella and Shigella multiply in medium consisting of 0.001 mm
      particles in 1% concentration similarly as in common growth media. The growth of
      Yersinia in medium of 0.05-mm corpuscles in 1% concentration was 3 Lg higher than
      in common growth medium. Bentonite media are cheap, easily available, and
      economic in comparison with common accumulation media.

PMID- 11521601
TI  - [Evaluation of endogenous intoxication by toxicouria using Tetrachimena
      pyriformis].

PMID- 11521602
TI  - [Genital infections in patients with radically treated cervix neoplasms].

PMID- 11521603
TI  - How can action research apply to health services?
AB  - The authors ask whether and how action research can apply to health services
      research, given action research's claim to be radically different from mainstream
      research. They analyze the key tenets of an idealized version of action research,
      comparing them with those of the approach characteristic of mainstream research.
      The authors conclude, firstly, that action research deserves all credit for
      pioneering flexible and imaginative ways of working. Yet, there is nothing in the
      fundamental logic of the mainstream approach to preclude it from adopting some of
      these. Action researchers therefore need to reconsider their critical stance
      toward mainstream research. Conversely, mainstream researchers need to reconsider
      their critical stance toward the ways of working pioneered by action research and
      to adopt them as appropriate.

PMID- 11521604
TI  - Health promotion and preventive measures: interpreting messages at midlife.
AB  - In this article, the authors provide important insight into the cultural messages
      that midlife women receive about preventive health care. Data were collected from
      24 rural women as part of an ongoing project on midlife women's health.
      Kleinman's model of the popular and professional health care sectors was used to
      examine the data. There is clear evidence of clashes between the orientations and
      expectations of these sectors. Women's experiences reveal some consistent themes
      that contextualize their preventive health pursuits: time constraints, claims for
      expert knowledge, salience of family history, and the inclusion of nonallopathic
      resources as part of the professional realm. At the macrolevel, messages
      regarding women's responsibility for their health are ubiquitous. At the
      microlevel, women must negotiate among competing messages and resources and a
      health care system that often confounds their efforts. These contradictions must
      be addressed before there are long-term effects on the health of midlife women.

PMID- 11521605
TI  - Social constructions of femaleness in writing about cancer.
AB  - This article uses a qualitative content analysis of writing about cancer since
      1900, with numeric summaries from Medline/PubMed searches, to propose that there
      is an implicit reliance in biomedicine on the idea that femaleness is
      pathological hence carcinogenic. Numeric summaries of rates of use of search
      terms for men and women and their sexual attributes are a backdrop for text
      sources that illustrate a greater tendency to see women in sexual terms and
      pathologize aspects of femaleness. This even extends into more frequent use of
      the term estrogen than testosterone in exclusively male cancer sites such as
      prostate and testicle. The analysis suggests that female focus and
      pathologization of femaleness come from social sex differentiation, heterosexual
      bias, and objectification of women as sex objects. This may be detrimental to
      both women and men because these social constructions may have focused cancer
      research on social classifications that are not physically relevant.

PMID- 11521606
TI  - Frontline talk: teachers' linguistic resources when talking about mental health
      and illness.
AB  - Talk about mental health and mental illness was examined using Potter and
      Wetherell's system of discourse analysis. Participants were 8 health coordinators
      (teachers) from a range of New Zealand secondary schools. They were interviewed
      on the topics of mental health and mental illness. Verbatim transcripts from the
      interviews were analyzed, and three mental health and illness linguistic
      resources were identified: a mental health as illness resource, a mental well
      being resource, and a mental illness resource. Each resource was examined, and
      the practical consequences of this language use was discussed in relation to the
      role of teachers as frontline mental health professionals.

PMID- 11521607
TI  - In the field with the Beck depression inventory.
AB  - Qualitative methods are typically and formally used only in the earliest phases
      of instrument development to generate items. Once these items are generated,
      instrument development usually then moves into the testing phases, where
      quantitative methods prevail. The achievement of psychometric credibility is
      presumed to depend largely on quantitative measures of reliability and validity.
      Or if qualitative methods are employed, their use is masked, unfocused, and/or
      unplanned. The planned use of qualitative methods is critical in every phase of
      instrument use and in all studies that depend for their results on instruments,
      and their use is critical in illuminating problems with existing instruments. The
      authors illustrate these points by drawing on the first author's experiences in
      the field with the Beck Depression Inventory in her research program on managing
      fatigue in persons with HIV/AIDS.

PMID- 11521608
TI  - The development of qualitative health research: taking stock.
AB  - The purpose of this article, which was a keynote presentation at the Qualitative
      Health Research Conference (QHR 2000) in Banff, Canada, is to provide a
      historical perspective of qualitative research in nursing over the past 20 years.
      Van Gennep's model of rites of passage is used as a heuristic. A discussion of
      the stages of stopping, waiting, transition, and entry is followed by speculation
      about the key characteristics necessary for qualitative research to be valued and
      valuable in the future.

PMID- 11521609
TI  - Validity in qualitative research.
AB  - Much contemporary dialogue has centered on the difficulty of establishing
      validity criteria in qualitative research. Developing validity standards in
      qualitative research is challenging because of the necessity to incorporate rigor
      and subjectivity as well as creativity into the scientific process. This article
      explores the extant issues related to the science and art of qualitative research
      and proposes a synthesis of contemporary viewpoints. A distinction between
      primary and secondary validity criteria in qualitative research is made with
      credibility, authenticity, criticality, and integrity identified as primary
      validity criteria and explicitness, vividness, creativity, thoroughness,
      congruence, and sensitivity identified as secondary validity criteria.

PMID- 11521610
TI  - Myth 94: qualitative health researchers will agree about validity.
AB  - In a recent editorial, Morse warned against qualitative health researchers
      turning their backs on fundamental concepts such as validity and called on them
      to think, reconsider, and undo. With a view to stimulating further dialogue, in
      this article the author explores where this thinking, reconsidering, and undoing
      might take us in relation to the concept of validity. Four perspectives on this
      issue are presented for discussion: the replication, parallel, diversification,
      and letting-go perspectives. Each is seen as worthy of consideration in its own
      right, and it is suggested that coexistence of the perspectives is possible
      despite their differences. The implications of various forms of coexistence are
      discussed in relation to the problem of criteria. It is recommended that
      qualitative health researchers learn to judge a variety of approaches in
      different but appropriate ways.

PMID- 11521611
TI  - Joint and individual interviewing in the context of cancer.
AB  - Joint interviewing lies somewhere between individual in-depth interviews and
      focus groups in the panoply of qualitative methodology, yet it has been little
      explored or described in health research. This article sets out to reflect on the
      process of choosing to combine joint and individual interviews in the context of
      a study on the needs of cancer patients and their carers. Questions of intrusion,
      inclusion, power, and difference caused the researchers to refine their research
      methods and become more responsive to the preferences of their participants. The
      article goes on to describe the kind of data generated by joint interviewing and
      to consider questions of analysis. The author concludes by suggesting that in
      appropriate circumstances, joint interviewing offers a valuable method of
      enquiry.

PMID- 11521613
TI  - Tingling rash in an older man.

PMID- 11521612
TI  - From meaning to meaning: the influence of translation techniques on non-English
      focus group research.
AB  - Language translation techniques are at the core of many cross-cultural
      qualitative research projects. The purpose of this article is to examine the
      impact of translation techniques on the collection and interpretation of non
      English to English qualitative data and, in particular, on focus-group data
      collection and analysis. The goal is to offer suggestions that will minimize
      potential threats to validity. This article includes a working definition of
      translation, a discussion of issues related to translation in quantitative
      research, a discussion of how translation issues differ in focus group research,
      evaluation criteria for translators and interpreters, and an example of
      translation techniques used in a research study of perimenopausal Hispanic women.

PMID- 11521614
TI  - Doors locked, heart open in a place of diversity and need.

PMID- 11521615
TI  - Sick building syndrome. Indoor air quality and your patients' health.

PMID- 11521616
TI  - The fainting patient. First and foremost, a meticulous evaluation.
AB  - It is sobering to consider the vast spectrum of causes of syncope. It is
      fortunate, however, that 30% to 74% of cases are assigned the correct cause on
      the basis of a thorough history and physical examination. However, a shotgun
      approach to evaluation is costly and may expose the patient to unnecessary risk
      and concern. Examples of diagnostic excess are routine CT scanning of the head
      and routine EEG, both of which have a very low yield on routine use. These
      procedures should only be used if they are necessary to answer questions raised
      by the initial evaluation.

PMID- 11521617
TI  - Witness a change of PA culture.

PMID- 11521618
TI  - "Will our baby be normal?" Answering questions asked by parents of premature
      infants.

PMID- 11521619
TI  - Help your patients surf the net safely.

PMID- 11521620
TI  - Are RNFAs a threat to PAs?
AB  - PAs are dependent practitioners, but that means we are an integral part of a
      team, and our value extends far beyond the operating room. Reimbursement for
      surgical services includes all services provided within a 60-day period of the
      operation. All care provided by a PA, therefore--care that an RNFA is neither
      trained nor allowed by law to perform--represents added value. Our presence and
      contribution save time, reduce the workload of the surgeon in and out of the
      operating room, and enhance care. Our mission, then, is to communicate our value
      not only to our employers but also to the hospitals in which we work and the
      communities that we serve. Are RNFAs a threat to PAs? As long as we remain
      multifaceted and promptly address misinformation disseminated about the PA
      profession, our value will speak for itself.

PMID- 11521621
TI  - Sorting out the common anemias.

PMID- 11521622
TI  - Evaluating an abnormal ECG. Reversed leads or cardiac trouble?

PMID- 11521623
TI  - A bullet in the head opened my eyes to the epidemic of youthful violence.

PMID- 11521624
TI  - Malaria--always a possibility in the febrile traveler or immigrant.

PMID- 11521625
TI  - When to screen for hepatitis C virus. Applying the principles of evidence-based
      medicine.

PMID- 11521627
TI  - Chicago yields the profession's biggest, busiest gathering.

PMID- 11521626
TI  - Diagnosing the mass in a child's painful foot.

PMID- 11521628
TI  - Coming home to treat deep venous thrombosis.

PMID- 11521629
TI  - A rural-urban comparison of patterns of physician assistant practice.
AB  - Access to primary care continues to be a concern in rural areas. The deficit of
      primary care providers in rural environments has the potential to increase the
      role of physician assistants (PAs) in the system of rural health care delivery.
      Little is known about the conditions, sites, and patterns of practice of PAs and
      their distribution in Pennsylvania, the state with the largest rural population.
      To learn more about these providers in rural and urban settings and their
      willingness to practice in underserved areas, the author conducted a census of
      all PAs who hold a Pennsylvania license. Survey results revealed significant
      rural-urban differences in socioeconomic, demographic, and practice profile
      parameters. Providers in rural areas are more likely than urban counterparts to
      practice primary care in a primary care practice setting; see more patients per
      week; and are the principal provider of care for a higher percentage of their
      patients. Experience with managed care is greater for urban PAs. A rural PA is
      more likely than an urban PA to practice in an underserved area. For both rural
      and urban PAs who practice primary care, significant differences were noted in
      their willingness to practice in a rural underserved area, compared to PAs who do
      not practice primary care.

PMID- 11521630
TI  - Pulmonary embolism. A difficult diagnosis demands an integrated approach.

PMID- 11521631
TI  - Diagnosis: your academy is strong and vibrant.

PMID- 11521632
TI  - A glimpse of Native Americans in the profession.

PMID- 11521633
TI  - The hospitalist PA: an emerging opportunity.

PMID- 11521634
TI  - Looking into tomorrow. Health workforce issues confronting physician assistants.
AB  - An important issue facing the physician assistant (PA) profession is how it can
      achieve a balance between supply of, and demand for, the services that PAs
      provide in the health workforce of the future. Recently, there has been debate
      and discussion about the implications of the recent expansion of the supply of
      PAs. In this article, we review and discuss (1) workforce data on physicians,
      PAs, and nurse practitioners and (2) projections of the number of these
      clinicians who will be trained in the future. We then analyze (1) data that
      describe the past 11 years of PA education and (2) data that address the
      experience of recent graduates of PA education programs who have sought
      employment. Some evidence suggests that, although demand has kept pace with
      expanding supply, a perception clearly exists that the PA job market may be
      tightening in some regions of the United States.

PMID- 11521635
TI  - Diastolic heart failure: management of an increasingly observed condition.

PMID- 11521636
TI  - Inside the VA, a difficult tour for PAs.

PMID- 11521637
TI  - In your practice. Recognizing child abuse and neglect.

PMID- 11521638
TI  - The sinister side of PA supply and demand.

PMID- 11521639
TI  - A linebacker with good cause for shoulder pain.

PMID- 11521640
TI  - The painful shoulder: is it impingement syndrome?

PMID- 11521641
TI  - Meralgia paresthetica. Case report in policewoman.

PMID- 11521642
TI  - How to choose between CT and MRI for musculoskeletal pain.

PMID- 11521643
TI  - Of osteoarthritis and venture capitalists.

PMID- 11521644
TI  - When speaking about imaging, image is everything.

PMID- 11521645
TI  - What are the management options for acute and chronic low back pain?

PMID- 11521646
TI  - Arthrocentesis to diagnose and treat acute gouty arthritis in the great toe.

PMID- 11521647
TI  - Why use intravenous filtration?

PMID- 11521648
TI  - The technological edge.

PMID- 11521649
TI  - Measuring pump performance.

PMID- 11521650
TI  - New guidance on the European declaration of conformity.

PMID- 11521651
TI  - Standards in the 21st century. Name that device!

PMID- 11521652
TI  - Welding and joining techniques.
AB  - There is a welding solution for most applications. As products must meet more
      stringent requirements or require more flexible processes to aid design or reduce
      cost, further improvements or totally new processes are likely to be developed.
      Quality control aspects are also becoming more important to meet regulation, and
      monitoring and control of welding processes and the standardised testing of
      joints will meet some if not all of these requirements.

PMID- 11521654
TI  - Switzerland. A hub of innovation.

PMID- 11521653
TI  - Plastic welding techniques based on torsional and circular motion.
AB  - The torsion ultrasonic welding process and the frequency decoupled circular
      friction process at low frequencies deliver low particle production. In addition,
      the even, circular movement of the circular welding process over the whole seam
      area and the freely selectable frequency open up applications in the medical
      field that cannot be achieved, or can only be achieved with difficulty, by
      traditional welding processes. The processes are fast and can be process
      controlled to a fine degree with a facility to be integrated into automation
      lines.

PMID- 11521655
TI  - New horizons for thermoplastic polymers.

PMID- 11521656
TI  - [Auditory neuropathy].
AB  - INTRODUCTION: Auditory neuropathy is a type of neurosensorial hypoacusis that
      produces significant impairment in language comprehension. Etiologically, this
      neuropathy has been related to perinatal hypoxia, hyperbilirubinemia, metabolic
      disorders and degenerative entities that affect the auditory pathway. PATIENTS
      AND METHODS: We report five children with this disorder. Two of the children were
      referred for otorhinolaryngeal assessment after failing the neonatal hearing
      screening and one was referred because of a history of perinatal hypoxia. The two
      eldest children were referred because of schooling problems and language
      impairment. In all the children, auditory brainstem response, otoacoustic
      emissions, tympanometry stapedius reflex were examined and liminal and condition
      orientation reflex audiometry were performed. After diagnosis, the children were
      followed-up for 3 consecutive years. RESULTS: In all five children, tympanogram
      and otoacoustic emissions were normal. The stapedius reflex and auditory
      brainstem responses with 80-90 dli stimuli were absent. Medium latency and
      conical and cognitive potentials were normal in the only child (aged 9 years) in
      whom they could be performed. In two children (aged 7 and 9 years), verbal
      discrimination was within the normal range for theft age. In all the children,
      audiometry revealed bilateral mild-to-moderate hypacusla, which did not change
      during follow up. CONCLUSIONS: Auditory neuropathy can be detected by the
      combined use of neonatal hearing screening techniques, auditory brainstem
      responses and otoacoustic emissions. Interest in the early identification and
      diagnosis of this disorder Is due to the clear benefit to language development
      secondary to the early treatment and rehabilitation of these children.

PMID- 11521657
TI  - [Control of a school outbreak of serogroup B meningococcal disease by
      chemoprophylaxis with azithromycin and ciprofloxacin].
AB  - OBJECTIVE: To assess the efficacy of azithromycin as a chemoprophylactic agent in
      meningococcal disease in pre-school aged children, and the safety of
      ciprofloxacin in children aged 6-16 years old. METHODS: After classic
      chemoprophylaxis with rifampicin failed to control a school outbreak of
      meningococcal disease in Cantabria (Spain), a second cycle of chemoprophylaxis
      was administered in the school. Azithromycin was administered in the nursery
      level (99 children, aged 3-5 years old) and ciprofloxacin was administered in the
      primary and secondary levels (795 children, aged 6-16 years old) and in the
      school's adult personnel (58 persons). The efficacy of chemoprophylaxis was
      studied through records of cases of meningococcal disease, the mandatory disease
      reporting system, and the school's absences. The safety of ciprofloxacin was
      studied using a questionnaire designed to determine the incidence of adverse
      osteoarticular effects, which was distributed to parents, school personnel and
      pediatricians within the school's area. RESULTS: The chemoprophylaxis
      administered controlled the outbreak. We collected 764 questionnaIres (response
      rate: 89.5 %). The incidence of arthralgia after ciprofloxacin was 0.9% in
      children and 3.3% in adults. All were mild and self-limiting without specific
      treatment, except in one patient (in the adult group) in whom arthralgia was
      present 1 month after prophylactic treatment. However, the arthralgia was so mild
      that the patient had not consulted her physician. Only three children had sought
      medical advice for arthralgia. Consequently, the incidence that would have been
      detected by the Spanish pharmacovigilance system would have been 0.4% in children
      and 0% in adults. CONCLUSIONS: Azithromycin was effective in controlling the
      outbreak in children aged between 3 and 5 years. Ciprofloxacin was safe and
      effective, with no serious or persistent osteoarticular effects in children. The
      incidence of arthralgia was lower in children than in adults.

PMID- 11521658
TI  - [Antiregurgitation formulas: are there any indications?].

PMID- 11521659
TI  - [Hyperthyroidism in newborn infants of mothers who had thyroidectomy for Graves'
      disease].

PMID- 11521660
TI  - [Fibrin net in the cerebrospinal fluid of children with tuberculous meningitis:
      an old, forgotten and effective method of early diagnosis].

PMID- 11521661
TI  - Where does DNA replication start in archaea?
AB  - Genome-wide measures of DNA strand composition have been used to find archaeal
      DNA replication origins. Archaea seem to replicate using a single origin (as do
      eubacteria) even though archaeal replication factors are more like those of
      eukaryotes.

PMID- 11521662
TI  - Neurobehavioral outcome of infants with sonographic lenticulostriate
      vasculopathy.

PMID- 11521663
TI  - Health care in blue and black and brown.

PMID- 11521664
TI  - Operational review: data and their analysis are essential.

PMID- 11521665
TI  - Operational reviews come in different shapes and sizes: the Regina Health
      District experience.

PMID- 11521666
TI  - Physician managers in the Canadian context.

PMID- 11521667
TI  - Matt Anderson, Chief Information Officer, University Health Network, Toronto,
      Ontario. Interview by Cynthia Martin.

PMID- 11521668
TI  - Privacy and publication.

PMID- 11521669
TI  - Climate change, air pollution and your health.

PMID- 11521670
TI  - Of needles, rituals, and injection behaviours: a comment on McBride et al.

PMID- 11521671
TI  - In dance scene drug surveys the sampling matters: comments on Riley et al.

PMID- 11521672
TI  - Joint heavy use of alcohol, cigarettes and coffee and the risk of suicide.

PMID- 11521673
TI  - Alcohol dependence treatment in Brazilian perspective.

PMID- 11521676
TI  - Bush stem cell decision limits research to existing cell lines.

PMID- 11521677
TI  - Baycol withdrawn from market.

PMID- 11521678
TI  - US Department of Health and Human Services gives states wider latitude in
      choosing services to be covered by Medicaid.

PMID- 11521679
TI  - Genome cartography through domain annotation.
AB  - The evolutionary history of eukaryotic proteins involves rapid sequence
      divergence, addition and deletion of domains, and fusion and fission of genes.
      Although the protein repertoires of distantly related species differ greatly,
      their domain repertoires do not. To account for the great diversity of domain
      contexts and an unexpected paucity of ortholog conservation, we must categorize
      the coding regions of completely sequenced genomes into domain families, as well
      as protein families.

PMID- 11521680
TI  - RuNAway Disease: A two cycle model for transmissible spongiform encephalopathies
      (TSEs) wherein SINE proliferation drives PrP overproduction.
AB  - BACKGROUND: Despite decades of research, the agent responsible for transmitting
      spongiform encephalopathies (TSEs) has not been identified. The Prion hypothesis,
      which dominates the field, supposes that modified host PrP protein, termed PrPSc,
      acts as the transmissible agent. This model fits the observation that TSE
      diseases elicit almost no immune reaction. Prion transmission has not been
      verified, however, as it has not been possible to produce pure PrPSc aggregates.
      One long-standing objection to the Prion model is the observation that TSE
      disease agents show classical genetic behaviours, such as reproducible strain
      variation, while also responding to selection for novel traits such as adaptation
      to new hosts. Moreover, evidence has been steadily accumulating that infectious
      titre is decoupled from the quantity (or even the presence) of PrPSc deposits.
      Rather awkwardly for the Prion hypothesis, PrP0/0 knockout mice have been found
      to incubate and transmit TSE agents (despite themselves being refractory to TSE
      disease). HYPOTHESIS: In this article, a new scheme, RuNAway, is proposed whereby
      uncontrolled proliferation of a type of parasitic gene, the small dispersed
      repeat sequences (SINEs), in somatic cells induces overproduction of PrP with
      pathogenic consequences. The RuNAway scheme involves twin tandem positive
      feedback loops: triggering the second loop leads to the pathogenic disease. This
      model is consistent with the long latency period and much shorter visible disease
      progression typical of TSEs.

PMID- 11521681
TI  - Life-style and serum lipids and lipoproteins.
AB  - In reviewing the trends and influences of life-style in this country on health
      and disease in the latter half of 20th century, we focused our attention on 4
      major habits of smoking, drinking, exercise and diets, and collected data on the
      Japanese to conduct a meta-analysis of their relationship with serum lipids and
      lipoproteins, which are the metabolic risk factors most closely related to
      atherosclerosis. 1) The percentage of smokers was 54.0% in adult males and 14.5%
      in adult females in 1999. In the data of 7,256 subjects (mean age 47 years) in 16
      papers, smoking increased triglycerides by 13 mg/dl (0.15 mmol/L) or in 559 non
      drinkers with a mean age of 49 years in 3 papers by 18 mg/dl (0.20 mmol/L), and
      decreased HDL-cholesterol by 3.5 mg/dl (0.09 mmol/L) with every 20 cigarettes
      smoked according to the regression equation. 2) As for drinking, the annual
      ethanol consumption per adult was 8.5L in 1996. The effects of alcohol on serum
      lipids were analyzed in 27,035 males (mean age 47 years) in 24 studies. Drinking
      elevated triglycerides by a mean of 10 mg/dl (0.11 mmol/L), and also HDL
      cholesterol by 2.5 mg/dl (0.06 mmol/L) per 23 g of alcohol intake (corresponding
      to 1 go of sake or 1 large bottle of beer). 3) Concerning exercise habit, 25% of
      males and 21% of females (mean age 47 years) regularly performed exercise such as
      jogging, swimming, aerobics, and tennis. However, walking was regarded as an easy
      exercise to be practiced by subjects of all ages. The effects of walking on serum
      lipids were studied in a total of 46,074 subjects (mean age 47 years) in 8
      populations. Triglycerides were significantly lower by 10 mg/dl (0.11 mol/L), and
      HDL-cholesterol higher by 3 mg/dl (0.08 mmol/L) in those who walked 6,000 or more
      steps/day than in those who walked less than 2,000 steps/day. The effects of
      harder exercise like jogging or swimming were analyzed in 2,242 subjects in 14
      papers (mean age 44 years). Triglycerides decreased by 10 mg/dl (0.11 mmol/L),
      and HDL-cholesterol elevated by 5 mg/dl (0.13 mmol/L) with an increase in the
      exercise intensity by one level of about 300 kcal. In exercise therapy,
      triglycerides were decreased by a mean of 20 mg/dl (0.23 mmol/L), and HDL
      cholesterol increased by a mean of 10 mg/dl (0.26 mmol/L) by exercise at a mean
      heart rate of about 135 bpm, which is equivalent to 50% VO2max for 30 minutes x 3
      times/week. 4) In nutritional trends, the mean energy intake in 52 postwar years
      averaged 2,116+/-84 kcal with no marked changes according to nutritional surveys.
      However, the percentage of fat in total energy intake was lowest at 7% in 1946,
      increased thereafter until it exceeded 20% in 1973, and surpassed 25% in 1988.
      The mean total cholesterol level of the Japanese increased by 28 mg/dl (0.72
      mmol/L) in the past 30 years and reached 204 mg/dl (5.28 mmol/L) in a survey in
      1990. 5) Concerning dietary habits, total cholesterol was lower by a mean of 13
      mg/dl (0.34 mmol/L), triglycerides lower by 40 mg/dl (0.45 mmol/L), and HDL
      cholesterol higher by 5 mg/dl (0.13 mmol/L) in the group who ate 7 or more
      Japanese-style meals in the 9 meals during 3 days than in the group who ate 3 or
      less Japanese-style meals in the 9 meals. When serum lipids were compared among
      individuals living in cities (8 groups; 3,613 subjects; mean age 51 years),
      agricultural villages (13 groups; 5,364 subjects; mean age 51 years), and fishing
      villages (9 groups; 1,071 subjects; mean age 52 years). Total cholesterol was
      lower by a mean of 10 mg/dl (0.26 mmol/L) in fishing villages than in cities, and
      triglycerides lower by a mean of 15 mg/dl (0.17 mmol/L) in fishing villages than
      in cities and agricultural villages. HDL-cholesterol was 5 mg/dl (0.13 mmol/L)
      higher in agricultural villages and 3 mg/dl (0.08 mmol/L) higher in fishing
      villages than in cities. 6) The effects of dietary therapy or guidance were
      evaluated in 585 subjects (mean age, 53 years) in 12 papers. Total cholesterol
      was reduced by 20 mg/dl (0.52 mmol/L), triglycerides by a mean of 40 mg/dl (0.45
      mmol/L), and HDL-cholesterol was increased by 5 mg/dl (0.13 mmol/L) by
      restriction of fat intake or restriction of the intake of saturated fat and
      dietary cholesterol. The results of these meta-analyses are considered to
      indicate the extent to which abnormalities of serum lipids are caused by a
      distorted life-style and the extent to which they are improved by correction of
      the life-style and exercise or dietary therapy. Correction of the life-style as a
      non-drug therapy may clearly improve hyperlipidemias or hypo-HDL-cholesterolemia
      so that this approach should be aggressively employed as part of the prevention
      and treatment for hyperlipidemias.

PMID- 11521682
TI  - Effect of bezafibrate treatment on the altered lipoprotein profiles in
      hypertriglyceridemic subjects.
AB  - The effects of bezafibrate treatment on lipoprotein metabolism were investigated
      in hypertriglyceridemic subjects. Bezafibrate, a fibric acid derivative, was
      administered at 200-400 mg/day to 8 patients with hyperlipoproteinemia (type IIb
      and IV) for 3-6 months. We evaluated the effects of bezafibrate on the plasma
      levels of total cholesterol(chol), triglyceride(TG), and apoB. In addition, the
      lipid and apoB contents were also analyzed in VLDL, IDL, LDL and HDL fractions
      before and after the treatment. It was revealed that plasma levels of chol, TG
      and apoB significantly decreased after the treatment, 236.3 vs 210.9,192.4 vs
      90.2 (p< 0.01) and 129.8 vs 116.2 (p<0.05) mg/dl respectively. VLDL-chol, VLDL-TG
      and VLDL-apoB dropped from 26.5,127.6 and 11.1 mg/dl to 9.1, 49.5 and 6.7 mg/dl
      respectively after the treatment. Regarding qualitative alterations of VLDL,
      TG/apoB, chol/apoB and TG + chol/apoB ratios in VLDL were significantly reduced,
      indicating that the size of VLDL was diminished by the treatment. In addition,
      HDL-chol increased from 40.4 to 60.8 mg/dl after the treatment. Consequently LDL
      chol/HDL-chol significantly decreased. In conclusion, bezafibrate administration
      decreased the TG, chol and apoB content in VLDL, suggesting a reduced number of
      VLDL. Significant rise of HDL-chol and decrease of LDL-chol/HDL-chol are
      additional beneficial effects following bezafibrate treatment.

PMID- 11521683
TI  - Regulation of hepatic high density lipoprotein binding protein, HB2, expression
      after administration of simvastatin to rabbits.
AB  - HB2 a candidate HDL receptor, is quite distinct from other HDL receptors in its
      structure. However, while changes in cellular cholesterol content, or a reduction
      in cholesterol biosynthesis accompany corresponding changes in HB2 expression,
      the level at which these changes occur have not been determined and the
      regulation and the function of HB2 remain uncertain. In order to further
      investigate the regulation of HB2, we administered simvastatin to rabbits to
      reduce cholesterol biosynthesis and follow changes in HB2 mRNA in various
      tissues. Six rabbits were given 15 mg/kg of simvastatin by oral administration
      daily and another six rabbits were given the same volume of saline as a control,
      for 21 days. They were then sacrificed to obtain samples of blood, liver, lung,
      jejunum and brain. Simvastatin reduced plasma total cholesterol by 47% and free
      cholesterol concentrations in liver and lung by 25 and 10%, respectively.
      Northern blot analysis showed that simvastatin lowered the expression of HB2
      significantly in the liver and lung by 54% and 42% respectively but not in the
      jejunum or brain. These results support the findings of a previous study showing
      that HDL binding activity of both HB1 and HB2, which was determined by ligand
      blotting using HDL3 as a ligand, were reduced after administering cholesterol
      lowering agents. (Arteriosclerosis, 10: 1045-1050,1990). The present study
      suggests that simvastatin down-regulated HB2 at the transcriptional stage.
      Although the complete physiological function of HB2 is unclear, it appears to
      play some role in the cholesterol metabolism, warranting further studies to
      elucidate the nature of this interaction.

PMID- 11521684
TI  - Hydrogen peroxide induced apoptosis of endothelial cells concomitantly with
      cycloheximide.
AB  - We examined whether or not hydrogen peroxide induced apoptosis of vascular
      endothelial cells. Cultured vascular endothelial cells from bovine carotid
      arteries were used. Apoptosis was determined by a propidium iodide assay. Under
      serum free conditions, treatment of the endothelial cells with hydrogen peroxide
      (H2O2) for 6 hours induced cytotoxicity (51Cr release) in a dose-dependent manner
      (10 micromol/l-1 mmol/l). Under the condition containing 10% serum, H2O2 did not
      induce cytotoxicity even at the highest concentration (1 mmol/l). However,
      concomitant treatment of endothelial cells with cycloheximide at a dose of 10
      microg/ml elicited endothelial cell apoptosis of by 15.6+/-1.7% at 6 hours after
      administration, even under the 10% serum condition. In addition, endothelial cell
      apoptosis due to H2O2 and cycloheximide was completely inhibited by zD-dcb (50
      micromol/l), an inhibitor of caspase. 1 mmol/l of 4, 4-diisothiocyanatostilbene
      2, 2-disulfonic acid (DIDS), which is a chloride bicarbonate exchanger blocker,
      partially inhibited the H2O2 and cycloheximide-induced endothelial cell
      apoptosis. On the other hand, cytotoxicity of endothelial cells due to H2O2 under
      serum free conditions was not inhibited by DIDS. These data suggested that
      hydrogen peroxide could induce endothelial cell apoptosis or cell membrane injury
      (51Cr release) in the presence or absence of an inhibitor of protein synthesis.

PMID- 11521685
TI  - Inhibition of low-density lipoprotein oxidation by astaxanthin.
AB  - Marine animals produce astaxanthin which is a carotenoid and antioxidant. In this
      study we determined the in vitro and ex vivo effects of astaxanthin on LDL
      oxidation. The oxidation of LDL was measured in a 1 ml reaction system consisting
      of increasing concentrations of astaxanthin (12.5, 25.0, 50.0 microg/ml), 400
      microM V-70 (2, 2'-azobis(4-methoxy-2, 4-dimethylvaleronitrile)), and LDL (70
      microg/ml protein). Astaxanthin dose, dependently significantly prolonged the
      oxidation lag time (31.5, 45.4, 65.0 min) compared with the control (19.9 min).
      For the ex vivo study 24 volunteers (mean age 28.2 [SD 7.8] years) consumed
      astaxanthin at doses of 1.8, 3.6,14.4 and 21.6 mg per day for 14 days. No other
      changes were made in the diet. Fasting venous blood samples were taken at days 0,
      +14. LDL lag time was longer (5.0, 26.2, 42.3 and 30.7% respectively) compared
      with day 0 after consuming astaxanthin at doses of 1.8, 3.6,14.4 and 21.6 mg for
      14 days compared with day 0, but there was no difference in oxidation of LDL
      between day 0 (lag time 59.9+/-7.2 min) and day 14 (57.2+/-6.0 min) in the
      control group. Our results provide evidence that consumption of marine animals
      producing astaxanthin inhibits LDL oxidation and possibly therefore contributes
      to the prevention of atherosclerosis.

PMID- 11521687
TI  - Elevated serum leptin concentrations in women with components of multiple risk
      factor clustering syndrome.
AB  - This cross sectional study was undertaken to determine whether serum leptin
      levels were associated with multiple risk factor (MRF) clustering syndrome. We
      examined the relationship between serum leptin concentrations and blood pressure
      (BP), serum lipids levels, calculated insulin resistance (HOMA-ratio) and
      adiposity among 581 Japanese adult women. The serum leptin was increased in
      female subjects with systolic (> or =160 mmHg) and diastolic > or =90 mmHg)
      hypertension compared with the normotensive females (mean+/-SE; 9.3+/-0.5 vs
      7.7+/-0.3; 10.2+/-0.6 vs 7.1+/-0.3 ng/ml, both p<0.001). Serum leptin was
      elevated in those with hyper-cholesterolemia (C; > or =220 mg/dl) and
      triglyceridemia (TG; > or =150 mg/dl) compared with the normolipidemia (9.4+/-0.4
      vs 7.8+/-0.3; 11.7+/-0.6 vs 7.5+/-0.2 ng/ml, both p <0.001). Serum leptin was
      also elevated in those with adiposity (BMI > or =26.4 kg/m2) and insulin
      resistance (HOMA-ratio > or =2.5) compared with the normal females (14.8+/-0.7 vs
      5.2+/-0.2; 11.3+/-1.1 vs 7.1+/-0.4ng/ml, both p<0.001). Even after adjusting for
      BMI or percent body fat mass (BFM), leptin levels remained to be elevated
      significantly in all these diseases. There was a positive correlation between
      serum leptin and systolic, diastolic BP, TC, TG, BMI, BFM, IRI and HOMA-ratio
      (r=0.12, p=0.005; r=0.24, p<0.0001; r=0.19, p<0.0001; r=0.35, p<0.0001; r=0.72,
      p<0.0001; r=0.73, p<0.0001; r=0.47, p< 0.0001; r=0.44, p<0.0001), and a negative
      correlation with HDL-C levels (r= -0.20, p< 0.0001). These correlations were also
      observed in leptin levels after adjusting for the BMI or BFM. Multiple regression
      analysis showed that BFM, HOMA-ratio and TG were significant determinants of
      leptin concentration before (t=12.6, p<0.0001; t=3.33, p=0.001; t=3.22, p=0.001)
      and after adjusting for BMI or BFM. These results suggest that because serum
      leptin levels were elevated in components of MRF clustering syndrome, leptin may
      have a pathophysiological role in MRF clustering syndrome.

PMID- 11521686
TI  - Gene expression induced by BO-653, probucol and BHQ in human endothelial cells.
AB  - 2, 3-Dihydro-5-hydroxy-2, 2-dipentyl-4, 6-di-tert-butylbenzofuran (BO-653) and
      probucol, which act as radical scavenging antioxidants, were developed as anti
      atherosclerotic medicines. In order to investigate the effect of these
      antioxidants on cell functions, we analyzed their ability to regulate gene
      expression in cultured human umbilical vein endothelial cells (HUVECs) using an
      oligonucleotide chip. Among 6,416 genes, 17 genes including those encoding
      mitochondrial proteins and proteins related to oxidative stress response were
      induced more than 3 fold by BO-653, probucol and tert-butylated hydroquinone
      (BHO). On the other hand, genes of three subunits of proteasome (PSMA2, PSMA3,
      PSMA4) were down-regulated by these antioxidants. A gene of cytochrome P-450 1A1
      isozyme, a drug-metabolizing phase I enzyme, was expressed only by BHQ treatment.
      These results suggested that anti-atherogenic antioxidants affected gene
      expression in HUVECs by which they might regulate cell functions against
      oxidative stress.

PMID- 11521688
TI  - Lysophosphatidylcholine enhances superoxide anions production via endothelial
      NADH/NADPH oxidase.
AB  - Reactive oxygen species (ROS) including superoxide anions (O2(-)) play a key role
      in atherogenesis, and endothelial cells have the ability to generate ROS. To
      investigate the enzymatic sources of ROS and the effects of
      lysophosphatidylcholine (LPC), an atherogenic lipid, we measured ROS production
      in cultured bovine aortic endothelial cells (BAECs) by the lucigenin-enhanced
      chemiluminescence (CL) method and electron spin resonance (ESR). BAEC homogenates
      had the enzymatic activity of NADH/NADPH oxidase. BAECs cultured on microcarrier
      beads generated O2(-) under basal conditions. The inhibition of NADH/ NADPH
      oxidase by diphenylene iodonium (DPI) significantly attenuated O2(-) production,
      whereas no inhibitors of other oxidases suppressed it. Although LPC enhanced O2(
      ) production approximately 3.1-fold, its action was suppressed by DPI. Tyrosine
      kinase inhibitors significantly attenuated LPC-induced O2(-) production. ESR with
      DMPO demonstrated that LPC increased the formation of the DMPO-hydroxyl adduct in
      dose- and time-dependent manners. These data suggest that the basal production of
      O2(-) in endothelial cells is mainly mediated by the NADH/NADPH oxidase system
      and that LPC activates this oxidase to enhance O2(-) production through a
      tyrosine kinase-dependent pathway. The enhancement of ROS production by LPC is
      probably involved in its atherogenic property.

PMID- 11521689
TI  - Three-dimensional optic nerve head algorithm for the detection of glaucomatous
      damage.
AB  - PURPOSE: To determine whether a three-dimensional optic disc algorithm could be
      useful in differentiating optic nerve heads (ONH) with a normal visual field from
      those with an abnormal visual field also when using a simultaneous stereoscopic
      computerised ONH analyser. METHODS: One eye was randomly chosen from 45 normals
      and 55 patients with glaucoma (mean deviation -7.7 +/- 9.0 dB, corrected pattern
      standard deviation 3.1 +/- 2.3 dB). All the subjects were examined with the
      Humphrey Perimeter (program 30-2) and with the Topcon Image-net X Rev-3.51 b.
      Using the topographic map of the system, the algorithm of the third moment or cup
      shape measure was applied to the numbers (the number of points ranged from 623 to
      1,883 depending on the size of the disc area) that identify the heights of all
      the points of the optic disc surface. Findings were analysed by means of the Mann
      Whitney U test and receiver operator characteristic curves. RESULTS: The
      sensitivity and specificity of this three-dimensional ONH algorithm applied to
      Topcon Image-net was 90.6% and 85.1% respectively. No difference was found
      between the groups for age, disc area and number of the analysed points.
      CONCLUSIONS: The algorithm of cup shape measure or third moment is a useful
      parameter to separate eyes with normal from those with abnormal visual field also
      when using a simultaneous stereoscopic system such as Image-net.

PMID- 11521690
TI  - Pars-plana vitrectomy in cystoid macular edema associated with intermediate
      uveitis.
AB  - BACKGROUND: Cystoid macular edema (CME) is a common complication in the course of
      intermediate uveitis. In spite of systemic therapy with steroids or carbonic
      anhydrase inhibitors, persistence of CME is observed. Pars plana vitrectomy (PPV)
      is known to influence the course of intermediate uveitis positively. The present
      study was performed to investigate the role of PPV in the therapy of CME in
      intermediate uveitis. MATERIALS AND METHODS: Forty-two eyes of 32 patients were
      re-examined after PPV for CME. In all eyes fluorescein angiography was performed.
      Average age at the time of surgery was 31.9 years (range 6-64 years). All
      patients had received systemic corticosteroid and/or immunosuppressive treatment
      during the course of their disease. In some patients systemic therapy with
      carbonic anhydrase inhibitors was performed. The mean duration of postoperative
      follow-up was 20.2 months (range 6-102 months). RESULTS: Preoperative visual
      acuity (VA) in all eyes was between 1/10 and 0.5. Total regression of CME after
      surgery was observed in 18 of 42 eyes (42.8%), partial improvement in 7 eyes
      (16.7%). In 13 of 42 eyes (30.9%) the CME remained unchanged. Twenty-one of 42
      eyes (50.0%) experienced a postoperative improvement of VA of 2 lines or more. In
      18 of 42 eyes (42.8%) there was no change; in 3 eyes (7.2%) VA was less. In the
      long-term follow-up the corresponding results were slightly worse (17/17/8 eyes)
      due to secondary complications. In the majority of patients systemic medical
      therapy could be reduced or discontinued. CONCLUSION: Pars-plana vitrectomy led
      to regression of CME in 59% of cases and to subsequent improvement of VA in 50%
      of eyes with intermediate uveitis. PPV should be considered soon after medical
      therapy has been shown to be ineffective.

PMID- 11521691
TI  - Transforming and insulin-like growth factors in the aqueous humour of patients
      with exfoliation syndrome.
AB  - BACKGROUND: Growth factors circulating with the aqueous may play an important
      role in the pathogenesis of exfoliation syndrome (XFS), which is characterized by
      excessive synthesis and accumulation of abnormal extracellular material. METHODS:
      We investigated the concentration of three ubiquitous growth factors (TGF-beta1,
      TGF-beta2 and IGF-1) in the aqueous humour of 50 patients with XFS (27 from
      Erlangen, 23 from Thessaloniki) and 54 age-matched controls (27 from Erlangen, 27
      from Thessaloniki). This study was performed in two centres, independently of
      each other, using different assay systems. RESULTS: In the aqueous humour samples
      collected in Erlangen, both the levels of total TGF-beta1 (P<0.001) and mature
      TGF-beta1 (P<0.05) were significantly increased in XFS patients compared with
      controls. Specifically, for total TGF-beta1 patients with XFS exhibited higher a
      mean value (90.5 +/- 37.4 pg/ml) than controls (30.2 +/- 8.3 pg/ml). The mean
      level of mature TGF-beta1 was also higher in XFS (14.2 +/- 2.8 pg/ml) than in
      controls (4.9 +/- 5.5 pg/ml). No difference was found between XFS and controls in
      the levels of total or mature TGF beta2 in the aqueous or in the level of these
      two growth factors in the serum. In aqueous humour samples collected in
      Thessaloniki a significant difference between XFS and controls was also observed
      for mature TGF-beta1 (XFS 17.06 +/- 11.02 pg/ml vs controls 9.01 +/- 5.69 pg/ml;
      P=0.006). No difference was observed in TGF-beta2 concentration or IGF-1
      concentration in the aqueous. No correlation could be established between protein
      concentration and the levels of the three growth factors measured. A significant
      correlation was found between age and protein concentration in XFS, but not in
      the controls. CONCLUSION: Since TGF-beta1 induces the synthesis and accumulation
      of extracellular matrix, it is hypothesized that TGF-beta1 plays an important
      role in the pathogenesis of XFS. Our data suggest that the increased levels of
      TGF-beta1 are most likely due to enhanced local synthesis.

PMID- 11521692
TI  - Alterations in expression of mucin, tenascin-c and syndecan-1 in the conjunctiva
      following retinal surgery and plaque radiotherapy.
AB  - PURPOSE: Disturbances of the ocular tear film layer and dry eye symptoms are
      common complications following retinal surgery and ocular tumour therapy.
      Examined were the histopathological changes of the conjunctiva following
      posterior segment surgery and plaque radiotherapy. METHODS: Biopsy specimens of
      the superior bulbar conjunctiva were obtained during cataract surgery between 2
      weeks and 7 years following vitrectomy (n=92) or plaque radiotherapy for uveal
      melanoma (n=20) and from control subjects without previous ocular surgery (n=29).
      These were examined using conventional histology (HE, PAS, Van Gieson) and
      immunochemistry [APAAP, using antibodies directed against MUC1, MUC5AC, syndecan
      1 and tenascin-C (TN-C)]. The histopathological changes were graded and
      statistical analysis was performed using Wilcoxon and Kruskal-Wallis rank sum
      tests. RESULTS: Conjunctival specimens of patients following vitrectomy or plaque
      radiotherapy for uveal melanoma demonstrated increased epithelial stratification,
      a significant decrease in the number of PAS- and MUC5AC-positive goblet cells,
      and distributional changes in expression of MUC1, syndecan- and TN-C within
      conjunctival epithelium or stroma. These alterations - in particular the goblet
      cell reduction and stromal fibrosis - were most prominent in those patients who
      had undergone radiotherapy. CONCLUSIONS: Posterior segment surgery can lead to
      morphological alterations of the conjunctiva and distributional changes in ocular
      mucins, which may cause dry eye symptoms.

PMID- 11521693
TI  - Retina-sparing laser treatment of occult CNV by vitrectomy and localised
      detachment of the macula.
AB  - BACKGROUND: Occult choroidal neovascularisation (CNV) was treated by a novel
      surgical approach. In order to spare the retina during laser photocoagulation of
      occult CNV, the retina was detached by subretinal infusion of a ringer solution.
      After localised detachment of the neural retina the CNV was transretinally
      coagulated by an endoprobe of a diode laser. METHODS: Twelve patients with occult
      CNV were treated in such a way. The mean duration of follow-up was 3.5 +/- 1.6
      months. After 4 weeks fluorescein angiography and indocyanine green angiography
      were performed in all patients. Laser exposure time was 1.1 +/- 0.7 s and laser
      energy was 1.2 +/- 0.7 W. RESULTS: In 10 of 12 patients the retina could be
      successfully detached and performed. In all cases the retina remained unchanged
      during laser photocoagulation. After 5 days subtle RPE atrophy and after 1 month
      obvious RPE atrophy was found. After 4 weeks, in 8 of 10 cases the CNV was
      completely occluded and no late leakage was found. Three months after operation,
      retinal atrophy could be seen in all cases. Visual acuity was lower in 6 and
      unchanged in 4 of 10 patients. CONCLUSION: Despite acute sparing of the neural
      retina the long-term effects are not better than after conventional laser
      photocoagulation, because secondary atrophy of the retina develops.

PMID- 11521694
TI  - Incidental retinal phototoxicity associated with ingestion of photosensitizing
      drugs.
AB  - BACKGROUND: to report on the possible correlation between incident retinal
      phototoxicity and the use of photosensitizing drugs. METHODS: four patients were
      examined because of scotomas and visual loss after an incidental exposure to a
      strong light source. One patient (two eyes) was exposed to standard camera flash;
      one patient (one eye) had a brief exposure to welding light; one patient (two
      eyes) underwent uncomplicated phacoemulsifications with intraocular lens
      implantation. The fourth patient had a severe retinal phototoxicity following a
      secondary intraocular lens implantation. All four patients underwent a thorough
      assessment including history of systemic drug use. These patients had
      ophthalmologic evaluation including: best corrected visual acuity (ETDRS charts),
      fundus examination, fluorescein and indocyanine green angiographies and were
      followed for 1 year. RESULTS: on presentation, the mean visual acuity was 7.5/20
      (range: 20/400-20/20). Fundus examination disclosed yellow-gray sub-retinal
      lesions in all affected eyes. Early phase fluorescein angiography showed one or
      multiple hypofluorescent spots surrounded by a halo of hyperfluorescent window
      defect. In the late phase, some of these spots leaked the fluorescein dye.
      Indocyanine green angiography demonstrated hypofluorescent spots throughout with
      ill-defined borders of hyperfluorescence observed during the late stages. The
      common finding in these four patients was the fact that they were all taking one
      or more photosensitizing drugs (hydrochlorothiazide, furosemide, allopurinol, and
      benzodiazepines). Three of the patients had a full visual recovery a few months
      after the phototoxicity. The fourth patient remained with a visual acuity of
      20/60 12 months after the light exposure. Despite the visual recovery, non
      homogeneous retinal pigment epithelial disturbances persisted in all affected
      eyes. CONCLUSION: phototoxicity following incidental light exposure may occur in
      patients taking drugs of photosensitizing potential. Therefore, the thorough
      history of systemic drug ingestion should be obtained if patients have exposure
      to strong light sources.

PMID- 11521695
TI  - Orbital presentations of giant cell arteritis.
AB  - BACKGROUND: giant cell arteritis (GCA) is a systemic vasculitis that may affect
      the optic nerve and cause blindness (e.g. ischemic optic neuropathy). Orbital
      inflammatory disease, however, is an uncommon presentation of GCA. PURPOSE: to
      alert clinicians to the orbital presentations of GCA. PATIENTS AND METHODS: a
      retrospective case series from tertiary care academic ophthalmic referral centers
      of four patients with orbital manifestations of giant cell arteritis. RESULTS:
      presentation of cases and review of the literature. In three cases, a temporal
      artery biopsy was diagnostic of GCA, but in one case, an orbital biopsy was
      needed to confirm the diagnosis. CONCLUSION: GCA can have orbital manifestations
      and clinicians should be aware of this unusual presentation of GCA in cases of
      presumed orbital inflammatory pseudotumor in the elderly.

PMID- 11521696
TI  - Impact of short-term versus long-term topical steroids on corneal
      neovascularization after non-high-risk keratoplasty.
AB  - PURPOSE: To analyze incidence and extent of corneal neovascularization (CN) after
      non-high-risk keratoplasty and to find out whether duration of postoperative
      topical steroid therapy (6 vs 12 months) affects CN, corneal endothelial cell
      count, pachymetry, aqueous flare values, and best-corrected visual acuity at 1
      year after keratoplasty. METHODS: Patients of the prospective Erlangen non-high
      risk keratoplasty study with available high-quality corneal photographs taken
      preoperatively and 1 year later were analyzed (n=136). Corneal photographs were
      evaluated by two independent observers in a standardized semiquantitative
      fashion. Slides were projected with 100x magnification and corneal vessels
      classified into five grades with regard to the limbus, sutures and host-graft
      junction in each of 12 corneal sectors. Incidence and extent of CN after
      keratoplasty and relation to short-term (0-6 months) versus long-term (0-12
      months) postoperative topical steroid therapy were analyzed. The effect of
      duration of topical steroid therapy on corneal endothelial cell count,
      pachymetry, aqueous flare values, and best corrected visual acuity was also
      analyzed. Of the 136 patients, 69 (51%) were randomly assigned to short-term and
      67 to long-term topical prednisolone acetate 1%. RESULTS: Fifty-eight percent of
      patients (n=79) developed a CN within 1 year after keratoplasty in at least one
      corneal sector (mean 3.1 +/- 2.2, range 1-10). At 1 year after keratoplasty, only
      in 12% of these patients did at least one vessel reach the host-graft junction or
      grow into the donor cornea, whereas in 51% vessels were seen beyond the outer
      suture ends of the double running suture without reaching the host-graft
      junction. In 37%, capillaries were located between limbus and outer suture ends.
      New vessels usually pointed directly or indirectly to the outer suture ends and
      usually were located around the 12 o'clock and 6 o'clock positions. There was no
      significant difference regarding incidence and extent of CN 1 year after
      keratoplasty between the long-term and the short-term group. Duration of topical
      steroid therapy had no significant effect on corneal endothelial cell count and
      thickness, aqueous flare values and best-corrected visual acuity at 6 and 12
      months postoperatively (only at 12 months, corneas in the long-term treatment
      group were slightly thicker; P=0.03). Interobserver correlation of vessel
      assessment was 0.77 (Kendall's tau B). CONCLUSIONS: CN is a common phenomenon
      after non-high-risk keratoplasty. New vessels rarely reach the host-graft
      junction, most commonly develop from the 6 o'clock and 12 o'clock positions and
      are usually located between epithelium and Bowman's layer (i.e., at the level of
      the superficial suture). The direction of vessel growth from the limbus towards
      the outer suture ends suggests release of angiogenic factors in this area.
      Prolongation of topical steroid therapy after non-high-risk keratoplasty beyond 6
      months in this study did not significantly influence incidence and extent of CN,
      corneal endothelial cell count, aqueous flare values and best-corrected visual
      acuity observed 1 year after keratoplasty.

PMID- 11521697
TI  - Comparative effects of antiglaucoma drugs on voltage-dependent calcium channels.
AB  - BACKGROUND: Experimental evidence suggests that substances able to interact with
      voltage-dependent Ca2+ channels (VDCCs) might be beneficial in glaucoma
      management. It was therefore of significance to show that beta-adrenoceptor
      antagonists used in glaucoma directly interact with L-type VDCCs. In the present
      study, the affinity of several antiglaucoma drugs (betaxolol, carteolol,
      levobunolol, timolol, brimonidine, dorzolamide, latanoprost and pilocarpine) for
      these and other VDCCs was investigated using radioligand binding assays.
      Experiments were also carried out to assess the effect of antiglaucoma drugs on
      the NMDA-stimulated Ca2+ influx into isolated rat retinas. METHODS: Competition
      radioligand binding studies to L-, N- and P/Q-type VDCCs were performed in rat
      cortical homogenates. The effects of antiglaucoma drugs on the NMDA-stimulated
      influx of 45Ca2+ were studied in isolated rat retinas. RESULTS: Only beta
      adrenoceptor antagonists significantly interacted with radioligand binding to L
      type VDCCs, with betaxolol displaying the highest potency. None of the
      antiglaucoma drugs tested showed any significant affinity for either N- or P/Q
      type VDCCs. Only beta-adrenoceptor antagonists attenuated the NMDA-stimulated
      45Ca2+ influx into isolated rat retinas, with betaxolol exhibiting at least 10
      times higher potency than timolol. Brimonidine, dorzolamide, latanoprost and
      pilocarpine did not elicit any significant effect on the NMDA-stimulated 45Ca2+
      influx. Additional experiments strongly suggested that the effect of betaxolol on
      the NMDA-stimulated 45Ca2+ resulted from inhibition of L-type VDCCs. CONCLUSION:
      Of the antiglaucoma drugs investigated, betaxolol displays the greatest L-type
      VDCC-blocking activity and this may be of clinical relevance. Such a
      characteristic could account for some of its described ocular actions.

PMID- 11521698
TI  - Migration of retinal pigment epithelial cells in vitro modulated by monocyte
      chemotactic protein-1: enhancement and inhibition.
AB  - BACKGROUND: The migration of retinal pigment epithelial (RPE) cells is an initial
      step in the development of proliferative vitreoretinopathy (PVR). This in vitro
      study was carried out to investigate the effects of monocyte chemotactic protein
      1 (MCP-1) on the migration and proliferation of RPE cells. METHODS: We used an in
      vitro wound healing model in which a small area of a confluent monolayer of human
      RPE (HRPE) cells was denuded with a razor blade. The cultures were subsequently
      incubated with MCP-1, IL-1beta, TNF-alpha, or combinations thereof. Neutralizing
      IgG1 of antihuman MCP-1, dexamethasone (DEX) or daunorubicin were also added to
      the cultures to test their inhibitory effects on migration of RPE cells. HRPE
      migration was measured as the number of cells that entered the denuded area. The
      effect of MCP-1 on proliferation of HRPE cells was examined by MTT assay.
      RESULTS: MCP-1 stimulated HRPE cell migration in a dose-dependent manner. IL
      1beta or TNF-alpha slightly stimulated HRPE cell migration, but adding anti-MCP-
      IgG1 significantly reduced this effect. MCP-1-induced migration could be
      inhibited by DEX but not by daunorubicin. MCP-1 did not show a significant effect
      on HRPE cell proliferation. CONCLUSION: MCP-1 stimulates HRPE cell migration,
      suggesting that this chemokine regulates the development of PVR at the initial
      stage. The migration of HRPE cells induced by IL-1beta and TNF-alpha may be
      associated with the MCP-1 that HRPE cells secretes under the stimulation of these
      two cytokines. The knowledge that MCP-1-induced migration of HRPE cells is
      inhibited by DEX may be useful in devising an effective treatment for PVR.

PMID- 11521699
TI  - Radiotherapy of exudative age-related macular degeneration; a clinical and
      pathologic study.
AB  - BACKGROUND: Radiotherapy has recently been employed to treat patients with
      exudative macular degeneration in order to prevent severe visual loss.
      Radiotherapy affects the evolution of exudative macular degeneration directly by
      endothelial toxicity, leading to capillary closure, and/or indirectly through its
      attenuating effects on the inflammatory response, mediated by macrophages and
      other inflammatory cells. METHODS: In this study we describe the histopathologic
      findings in a patient with exudative age-related macular degeneration (AMD) in
      both eyes whose right eye was treated with radiotherapy (5 times 2 Gy) 3 years
      before he died. The eyes were enucleated post mortem and investigated by light
      microscopy. Additionally, immunohistochemical investigation with antibodies
      against CD34 and CD68 was performed to identify patent endothelial cells and
      macrophages. RESULTS: Both eyes showed neovascular AMD consisting of mixed
      fibrocellular and fibrovascular membranes. Capillaries in both the
      choriocapillaris and the neovascular membrane were patent in both eyes.
      Macrophages were present in the choroidal neovascularization of both eyes.
      Neither preexistent choroidal, intraretinal, nor neovascular vessels showed
      increased wall thickness as sign of radiation damage. CONCLUSION: No radiation
      related histopathologic effect could be demonstrated 3 years after radiation
      therapy in this patient with AMD.

PMID- 11521700
TI  - Clinical-pathologic correlation in Coats' disease.

PMID- 11521701
TI  - Minimally invasive internal fixation history, essence and potential of a new
      approach.

PMID- 11521702
TI  - Minimally invasive reduction and osteosynthesis of articular fractures of the
      distal radius.
AB  - Treatment of displaced fractures of the distal radius has changed over the course
      of time. For many years, closed reduction with plaster immobilization was
      considered the treatment of choice. Subsequent use of pins and plaster,
      percutaneous pin fixation, and the development of external fixation devices all
      contributed to improving fracture stability. More recently a new generation of
      external fixation devices has been developed to permit distraction and palmar
      translation. In addition, over the past twenty years, we have seen the
      development of more sophisticated internal fixation devices for the treatment of
      displaced fractures of the distal radius. The indications for open reduction and
      internal fixation have been defined largely on the basis of numerous studies
      which support the concept that articular malreduction is predictive of traumatic
      arthritis and poor functional result. Knirk and Jupiter have reported poor
      results for intra-articular fractures of the distal radius having an articular
      step-off greater than 2 mm. More recently, wrist arthroscopy has been used to
      improve visualization of articular surfaces and aid fracture reduction. In
      addition, bone grafting techniques have been employed more frequently to
      accelerate fracture healing. With improvement in techniques, we are able to
      provide our patients with better functional results and return them to their
      activities of daily living and vocation more rapidly.

PMID- 11521703
TI  - Minimally invasive reduction and osteosynthesis of articular fractures of the
      humeral head.
AB  - Percutaneous reduction and fixation of severe humeral head fractures would be the
      treatment of choice since it will not increase the risk of necrosis already
      inherent in these fractures. Nevertheless, the question arises of whether
      anatomical reduction is possible with the percutaneous technique and whether the
      reduced fracture can be adequately stabilized. It is important to study the
      fracture closely before the operation in order to determine the fracture type and
      identify the relationship of the individual fragments to each other. Radiographs
      taken in at least two planes are essential and a CT scan with 3D reconstruction
      would be desirable. Besides extraarticular fractures, surgical neck fractures
      with avulsion of the greater tuberosity (B1 and B2 fractures) and valgus impacted
      fractures (C1 and C2 fractures) are good indications for this method due to the
      fact that in these cases intact connections to rotator cuff tendons or remnants
      of intact periosteum between fragments still exist. Less good indications are
      fractures with severe lateral displacement of the articular segment and severely
      displaced fracture dislocations (C2 and C3 fractures). From 1990 to 1999, a total
      of 88 patients with 37 B1 and B2 fractures and 41 C1 and C2 fractures were
      operated on percutaneously. The initial 27 patients with 9 B1 and B2 and 18 C1
      and C2 fractures were followed up. All B1 and B2 fractures showed good to very
      good functional results (Constant Score 91%). The Constant Score of the C1 and C2
      fractures was 87%. The necrosis rate of the C1 and C2 fractures was 11%. In
      conclusion, it can be said that the presence of soft tissue bridging of the
      various fragments is crucial for the reduction to gain benefit from the
      ligamentotaxis effect. Thus, fractures such as valgus impacted or three-part
      fractures are very good indications for this technique. It can also be stated
      that the necrosis rate is low or at least not increased compared to cases treated
      by open reduction. Since the fracture is not exposed, adhesion within the
      surrounding gliding surfaces is reduced and the rehabilitation period is shorter.

PMID- 11521704
TI  - Percutaneous management of unstable pelvic ring disruptions.
AB  - Percutaneous pelvic fixation stabilizes pelvic ring disruptions without extensive
      pelvic dissection. For this reason, these anterior and posterior percutaneous
      pelvic fixation techniques allow acute and definitive treatment. Successful
      percutaneous pelvic fixation techniques depend on accurate closed reduction,
      excellent intraoperative fluoroscopic imaging, and detailed preoperative
      planning. Early pelvic stability diminishes haemorrhage, provides patient
      comfort, and allows early patient mobilization from recumbency.

PMID- 11521705
TI  - A minimally invasive medial approach for proximal tibial fractures.
AB  - Numerous techniques have been described for MIPPO (minimally invasive
      percutaneous plate osteosynthesis) for metaphyseal or combined metaphyseal
      articular fractures of the proximal tibia. Surgical management is often
      complicated by the initial soft tissue damage, malalignment, remaining
      instability, or infection. In this prospective cohort study, we describe the
      diagnostic procedures vital for preoperative planning. These include plain
      radiographs and CT scans in case of articular fracture components. The techniques
      for temporary stabilization and definitive fracture care using 4.5 mm DCP, LC
      DCP, and LISS (Less Invasive Stabilization System) by limited medial incisions
      are described in a stepwise protocol. From 1996 to 1998, six fractures in six
      patients were studied. According to the AO classification, there were four type
      41 fractures and two type 42 fractures. One patient died of ARDS. All patients
      had an intact medial soft tissue coverage allowing a medial approach. One patient
      developed a compartment syndrome, which was addressed by lateral dermato
      fasciotomy prior to osteosynthesis. A LISS was used in three patients. The only
      complication related to surgery was in a patient with a four-part fracture with
      lateral comminution and a dislocated postero-medial fragment, which was reduced
      and buttressed with a short posteromedial 3.5 mm small fragment plate. This
      patient developed a deep, intraarticular infection, which was successfully
      treated with revision surgery; the implants were left in situ. At her latest
      follow-up at 18 months, she had a range of motion of 0/10/110, was back at work,
      and able to participate in recreational sports. The average time to healing was
      between 12 and 20 weeks postoperatively. There was no delayed healing,
      pseudarthrosis, recurrent fracture or late infection. None of the cases needed
      bone grafting. At the most recent follow-up, all patients were bearing full
      weight without walking aids. All cases achieved a neutral alignment and
      satisfactory range of movement. Though further data are needed we have sound
      reason to propagate a single medial approach and minimally invasive
      osteosynthesis as a sufficient and subtle technique for stabilization of these
      complicated fractures.

PMID- 11521706
TI  - Preliminary results and complications following limited open reduction and
      percutaneous screw fixation of displaced fractures of the acetabulum.
AB  - Twenty-four patients underwent attempted closed or limited open reduction of
      displaced acetabular fractures. If reduction was successful, the fractures were
      stabilized with percutaneous screws. Group 1 was composed of elderly patients
      with complex fractures and radiographic findings that were felt to be predictive
      of post-traumatic arthritis. In these patients, percutaneous screw fixation was
      used to improve fracture anatomy, allow mobilization and total hip replacement
      later, if necessary. In group 1, anatomical reduction was not felt to be a
      necessity. Group 2 was composed of young patients with simple fracture types. For
      group 2, anatomical reduction was the goal. In 23/24 patients, closed or limited
      open reduction was successful. In group 1, maximum displacement averaged 10 mm
      preoperatively, 3 mm postoperatively. In group 2, maximum displacement averaged 7
      mm preoperatively, 1 mm postoperatively. One elderly patient was lost to follow
      up and one died, leaving 21 patients with an average follow-up of 12 months. All
      the fractures healed. One patient had a transient femoral nerve palsy, and two
      elderly patients had minor losses of reduction due to unprotected ambulation
      after surgery. Five of the elderly patients have gone on to total hip
      arthroplasty. The average Harris Hip scores in groups 1 and 2 were 85 and 96,
      respectively.

PMID- 11521707
TI  - An introduction to the minimally invasive osteosynthesis of intra-articular
      calcaneal fractures.
AB  - The approach to the treatment of intra-articular calcaneal fractures has often
      been the subject of discussion. The results achieved with both operative and non
      operative management remain to some extent unpredictable. Minimally invasive
      osteosynthesis offers an alternative approach, especially in those cases in which
      open reduction would be hazardous and non-operative treatment inadequate. This
      technique requires minimal dissection and preserves subtalar motion almost
      completely. The authors believe that displaced intra-articular calcaneal
      fractures are best treated through operative intervention. Restoration of
      articular congruity is an integral, though not necessarily sufficient, component
      of a successful long-term outcome following calcaneal fracture. The extra
      articular dimensions of the calcaneus must be restored in order to tolerate
      standard shoe-wear, maintain a functional range of talocalcaneal motion and avoid
      subsequent tibiotalar arthrosis. However, in certain circumstances open reduction
      may be associated with an unacceptably high complication rate. In these cases,
      the authors have found a "minimally invasive" osteosynthesis technique useful in
      dealing with competing goals. In our experience, this technique can, when used
      appropriately, result in a functional recovery of the patient suffering a
      calcaneal fracture.

PMID- 11521708
TI  - The pure-tone hearing thresholds of otologically healthy 14-year-old children.
AB  - The mean pure-tone air conduction (AC) and bone conduction (BC) hearing
      thresholds (HT) of 534 randomly selected, caucasian, white, urban children with
      normal otoscopy, otomicroscopy and impedance audiometry, i.e. normal middle ear
      function, are presented here. Children with pathological middle ear findings or
      abnormal impedance audiometry were excluded. The average age was 13.8 years, SD
      0.5, at the date of examination. The mean air conduction thresholds varied
      between 0.6 dB at 1 kHz and 9.9 dB at 6 kHz, and the bone conduction thresholds
      varied between -1.1 dB at 0.5 kHz and 1.1 dB at 4 kHz. The pure-tone average
      (PTA) (the average of AC hearing thresholds of 0.5, 1 and 2 kHz) of all ears was
      1.5 dB. Ninety to ninety-eight per cent of pure-tone AC hearing thresholds at
      frequencies of 0.5-4 kHz were between -5 dB and 10 dB. The distributions are
      presented and compared.

PMID- 11521709
TI  - Normative values for tympanometry in 7- and 24-month-old children.
AB  - The objective was to determine normative values for tympanometric variables for 7
      and 24-month-old children and to assess the effect of various factors on these
      variables. Tympanometry was performed at scheduled health visits at 7 and 24
      months of age on children recruited to a prospective vaccine efficacy trial
      (n=2497 children at enrolment). Tympanograms obtained successfully from healthy
      ears with no recent otitis media were analysed. Normative values for static
      acoustic admittance (SAA), tympanometric peak pressure (TPP) and tympanometric
      width (TW) were calculated. The mean SAA was 0.25 cm3 at the 7-month visit
      compared to 0.34 cm3 at the 24-month visit. The TW decreased and TPP remained
      unchanged with age. Higher SAA values were found in boys. A history of recurrent
      acute otitis media and history of tympanostomy tubes were found to increase SAA
      and decrease TW at 24 months. In conclusion, age-specific normative values for
      interpretation of SAA and TW are necessary.

PMID- 11521710
TI  - Tympanic membrane displacement analyser tracing modifications induced by glycerol
      in Meniere's disease.
AB  - The aim of the study was to detect inner ear fluid pressure changes induced by
      glycerol in Meniere's disease (MD) by means of a tympanic membrane displacement
      analyser (TDA). The study group consisted of 25 MD patients. The Vi (maximum
      inward displacement of the tympanic membrane) and the Vm (mean displacement of
      the tympanic membrane) were measured at 10, 20 and 25 dB above the stapedial
      reflex threshold. Each patient received therapy based on glycerol. The control
      group consisted of 20 patients with non-hydropic sudden hearing loss. At 20 and
      25 dB above stapedial threshold MD patients had lower Vi values before therapy.
      After glycerol, we observed a Vi increasing in the hydropic ears in 68-96 per
      cent of patients. Since a Vi improvement implies a reduction of perilymph
      pressure, our results confirm the effectiveness of Vi in detecting specific
      action of glycerol in MD.

PMID- 11521711
TI  - Computer-assisted ABR interpretation using the automatic construction of the
      latency-intensity curve.
AB  - In this paper, we present a new computerised technique for the automatic
      construction of the latency intensity curve (LI curve). We take a pattern
      recognition approach determined by a priori information. We use knowledge gained
      from the audiogram and from physiological considerations. Therefore, we consider
      all recordings at different intensities as well as results from the extraction of
      a single auditory brainstem response (ABR) at a given stimulus intensity. We
      tested our method successfully: it allows us to prevent misrecognition errors in
      response detection or in latency measurements. Automatic recognition of the waves
      and recognition by the ear, nose and throat (ENT) specialist coincided in at
      least 90 per cent of cases. For wave V, the average deviation between the
      response thresholds given by our automatic recognition algorithm and those given
      by the ENT specialist was 5 dB, and the average deviation of the latencies was
      0.05 ms.

PMID- 11521712
TI  - Comparing signal to noise ratios of amplitude modulation following responses from
      four EEG derivations in awake normally hearing adults.
AB  - Amplitude modulation following responses (AMFR) or steady-state evoked potentials
      (SSEPs) can be used for the objective and frequency-specific estimation of
      hearing thresholds in awake and sleeping subjects. To be useful as a clinical
      tool, a high signal to noise ratio (SNR) is required for a minimal testing time.
      Four EEG derivations were compared in six relaxed, cooperative awake normally
      hearing adults to compare the SNRs. Stimuli comprised a 1 kHz carrier wave,
      amplitude modulated at 39 Hz and 90 Hz. They were presented for about 4.4 min in
      one ear at a level slightly above the behavioural threshold (10 dB SL). In the 39
      Hz condition, the SNRs from the different derivations did not differ
      significantly. However, in the 90 Hz condition one novel derivation (Cz-inion
      with ground at Pz) yielded a significantly lower noise level, about 60 per cent
      of the noise level of the other derivations. The SNR of this derivation was about
      50 per cent larger than from other derivations. Such an increase of the SNR
      implies that testing time is reduced by about 56 per cent as compared to
      conventional derivations in these subjects.

PMID- 11521713
TI  - Some experiences with hearing disability/handicap and quality of life measures.
AB  - To achieve detailed information on the outcome of hearing rehabilitation in a
      clinical setting, measurements of hearing disability and hearing handicap have
      been introduced, and the present study describes the preliminary experiences with
      these measures in a series of hearing-impaired subjects referred for audiological
      evaluation. To outline hearing disability/hearing handicap (HD/HH), before
      continuation or initiation of treatment, the Gothenburg profile and a generic
      health-related quality of life--the SF-36 questionnaire--were used to evaluate
      any adverse effects resulting from hearing disorders. The Gothenburg profile and
      the SF-36 questionnaire were mailed to 634 subjects appointed for audiological
      examination with a request to complete the questionnaires at home. Three
      questions were enclosed concerning the capacity to complete the questionnaires,
      showing that 1.9 per cent were incapable of completing them, 17.5 per cent needed
      assistance, 43.5 per cent completed the questionnaires, and 37.1 per cent did not
      respond to them. Thus the response rate was only 55.5 per cent and, in addition,
      these responses were characterised by missing data. An arbitrary criterion of an
      average score per question of >3 for the averaged HD and HH items respectively
      was applied, resulting in 72.7 per cent indicating HD, whereas 30.3 per cent
      indicated HH according to the items in the profile. Significant differences in
      hearing levels were found between those experiencing HD and HH having a score >3
      and those with a score <3. When analysing the general health status, general
      perception of health and social functioning, significantly lower scores were
      found for those experiencing HD/HH, whereas no significant differences were found
      between the total sample of hearing-impaired subjects and the age-matched
      population for these parameters. It is concluded that the present procedure
      cannot be implemented as a routine outcome measure in a clinical setting and
      alternative outcome measures should be considered.

PMID- 11521714
TI  - HER2--a discussion of testing approaches in the USA.
AB  - HER2 (neu, erbB-2), a receptor related to the human epidermal growth factor
      receptor, has now become more important as a predictive marker of treatment
      response. While the value and direction of the treatment/HER2 interaction may
      vary, depending on the agents, dose, or schedule of drug administration, there is
      little disagreement that HER2 testing is an important part of breast cancer
      evaluation. In 1998, trastuzumab (Herceptin) was approved for the treatment of
      HER2-positive metastatic breast cancer patients by the Food and Drug
      Administration of the USA. Patients with abnormal HER2 in their breast cancer
      cells (generally 2 or 3+ with the HercepTest, overexpression by other
      immunohistochemical assays or amplification by fluorescence in situ hybridization
      [FISH] assay) have demonstrated the greatest response to trastuzumab treatment.
      It is unclear which test (method, reagent, cut-off points, etc.) is best to use
      to evaluate HER2 for this purpose because parallel testing of the same cancers
      from patients who received trastuzumab has only recently been initiated and the
      data are limited. It is widely believed that breast cancers without HER2
      alterations will not be responsive to trastuzumab, although a clinical trial to
      test this specific hypothesis has not been initiated. There are also concerns
      that clonal heterogeneity for HER2 within a tumor, or between primary and
      metastatic cancer foci, may affect treatment response; yet we do not currently
      evaluate these parameters. Consensus regarding the best methods, reagents, or cut
      off points to define HER2 status for determining trastuzumab responsivity has not
      yet been reached. HER2 testing for other prognostic or predictive purposes, e.g.
      to determine whether patients are likely to respond to other agents, such as dose
      intensive doxorubicin, may be less. Data from the Cancer and Leukemia Group B
      trial 8541 (companion 8869) suggest that, with proper controls in high-volume
      laboratories, many of the available methods produce comparable results.

PMID- 11521715
TI  - HER2 overexpression in various tumor types, focussing on its relationship to the
      development of invasive breast cancer.
AB  - To date, poor standardization in HER2 status evaluation has precluded reliable
      comparison of overexpression rates in different tumors. However, standardized
      methodologies have been introduced recently for these analyses, and have
      identified frequencies of 51%, 44%, 26% and 25% in Wilm's tumor, bladder,
      pancreatic and breast carcinoma, respectively. Other tumors tested had
      frequencies below 20%. The frequency was greater than that predicted by gene
      amplification data in some tumor types, which may indicate overexpression due to
      gene deregulation, rather than gene amplification. Analysis of a large
      retrospective series of breast carcinomas demonstrated an association between
      HER2 positivity and a number of other prognostic markers. Together, these
      variables identify a subset of tumors with poor prognosis and early relapse post
      surgery. HER2 expression is relatively stable, with 95% concordance between the
      HER2 status of primary and metastatic lesions. However, contralateral tumors are
      unrestricted with regard to HER2 status. Preliminary data indicate that the HER2
      status of a hormone receptor-positive tumor may fluctuate according to the
      menstrual cycle. It is anticipated that the emerging wealth of standardized data
      for HER2 status will help to elucidate the role of HER2 in tumor progression.

PMID- 11521716
TI  - Modulation of p27/Cdk2 complex formation through 4D5-mediated inhibition of HER2
      receptor signaling.
AB  - The molecular mechanisms mediating the anti-proliferative effects of the murine
      anti-HER2 monoclonal antibody (4D5) were investigated in HER2-overexpressing
      human carcinoma cell lines. Treatment with 4D5 resulted in a dramatic
      accumulation of BT-474 breast carcinoma cells in G1; concomitant with reduced
      expression of proteins involved in sequestration of the cyclin E/Cdk2 inhibitor
      protein p27, increased association of p27 with Cdk2 complexes and Cdk2
      inactivation. No equivalent effects were observed in BT-474 cells treated with a
      control, non-inhibitory HER2 monoclonal antibody (FRP5) or in a HER2
      overexpressing cell line insensitive to 4D5 treatment (MKN7 gastric carcinoma
      cells), confirming the relationship between these molecular changes and 4D5
      mediated inhibition of proliferation. Increased p27 expression was also observed
      in 4D5-treated BT-474 cells; however an antisense approach demonstrated that this
      increase was not required for Cdk2 inactivation or establishment of the G1 block.
      These data suggest that 4D5 interferes with HER2 receptor signaling, resulting in
      downregulation of proteins involved in p27 sequestration. This causes release of
      p27, allowing binding and inhibition of cyclin E/Cdk2 complexes and inhibition of
      G1/S progression. This model was confirmed using a second 4D5-sensitive. HER2
      overexpressing breast tumor line (SKBR3), and suggests that the dependency of a
      given tumor cell on elevated HER2-receptor signaling for the maintenance of p27
      sequestration proteins may determine the clinical response to treatment with the
      humanized anti-HER2 monoclonal antibody Herceptin (trastuzumab).

PMID- 11521717
TI  - HER2 as a prognostic and predictive marker for breast cancer.
AB  - In recent years investigators have looked at the human epidermal growth factor
      receptor-2 (HER2), which is overexpressed in 20%-30% of breast cancer patients,
      with regard to its role as a prognostic and predictive factor. Although many
      studies have suggested that HER2 overexpression may be associated with a poor
      clinical outcome, other studies have not fully supported this observation. The
      inconsistencies between studies may be due in part to discrepancies between
      different HER2 testing methods. To overcome this problem, a
      radioimmunohistochemical method was developed to quantitatively measure HER2
      overexpression levels in breast tumor samples. The application of this method
      demonstrated that 85% of all breast tumor samples expressed HER2 at levels
      greater than normal. Of these, 23% expressed HER2 at levels between 45 and 480
      times greater than normal, and this was associated with poor clinical outcome.
      The investigation of HER2 status as a predictor of response to therapy has also
      yielded many conflicting results. Overall, it appears that HER2 overexpression
      may correlate with resistance to hormonal therapy, sensitivity to anthracycline
      based chemotherapy and resistance to CMF. With the development of targeted anti
      HER2 therapies, assessment of HER2 status will be important in stratifying
      patients to the most appropriate treatment regimens.

PMID- 11521718
TI  - HER2 status: a statistician's view.
AB  - The human epidermal growth factor receptor-2 (HER2) has been investigated as a
      prognostic and predictive factor in breast cancer. The studies undertaken have
      included retrospective subset analyses and this had led to problems with bias
      such that only marginal statistical significance can be given to the results
      obtained. Overall, the majority of studies have found that a HER2-positive status
      may predict a poor patient outcome. although some studies have contradicted this
      finding. As a predictor of response to treatment, the results on the value of
      HER2 status are less well defined. Many studies suggest that a HER2-positive
      status correlates with resistance to hormonal therapy. Furthermore, a number of
      studies have found that a HER2-positive status is associated with a relative
      resistance to CMF (cyclophosphamide. methotrexate, 5-fluorouracil) and
      chemosensitivity to anthracycline-based therapies. However, there are enough
      discrepancies between studies for the predictive value of HER2 status to be
      unproven at the present time. Large, well-defined and accurately reported
      prospective studies are required to determine with any statistical clarity the
      value of HER2 status as a prognostic or predictive factor in breast cancer. In
      the meantime, no therapeutic option should be overlooked based solely on the HER2
      status of a patient.

PMID- 11521719
TI  - The basic biology of HER2.
AB  - Human epidermal growth factor receptors (HER/erbB) constitute a family of four
      cell surface receptors involved in transmission of signals controlling normal
      cell growth and differentiation. A range of growth factors serve as ligands, but
      none is specific for the HER2 receptor. HER receptors exist as both monomers and
      dimers, either homo- or heterodimers. Ligand binding to HERI, HER3 or HER4
      induces rapid receptor dimerization, with a marked preference for HER2 as a dimer
      partner. Moreover, HER2-containing heterodimers generate intracellular signals
      that are significantly stronger than signals emanating from other HER
      combinations. In normal cells, few HER2 molecules exist at the cell surface, so
      few heterodimers are formed and growth signals are relatively weak and
      controllable. When HER2 is overexpressed multiple HER2 heterodimers are formed
      and cell signaling is stronger, resulting in enhanced responsiveness to growth
      factors and malignant growth. This explains why HER2 overexpression is an
      indicator of poor prognosis in breast tumors and may be predictive of response to
      treatment. HER2 is a highly specific and promising target for new breast cancer
      treatments. The recombinant human anti-HER2 monoclonal antibody (rhuMAb-HER2,
      trastuzumab, Herceptin) induces rapid removal of HER2 from the cell surface,
      thereby reducing its availability to heterodimers and reducing oncogenicity.

PMID- 11521720
TI  - Mechanism of action of anti-HER2 monoclonal antibodies.
AB  - The search for new methods of treating cancer, combined with advances in our
      understanding of carcinogenesis, molecular biology and technology, has resulted
      in the development of novel biologic agents with proven clinical efficacy. One
      such agent is trastuzumab (Herceptin), a humanized monoclonal antibody that
      targets the human epidermal growth factor receptor-2 (HER2). HER2 is a member of
      a family of receptors that interact with each other and various ligands to
      stimulate various intracellular signal transduction pathways involved in cell
      growth control. HER2 is overexpressed in 20%-30% of women with breast cancer and
      is associated with aggressive tumor characteristics and poor prognosis.
      Trastuzumab is the first humanized monoclonal antibody to be approved for
      therapeutic use and the first oncogene-targeted treatment with proven survival
      benefit in women with HER2-positive metastatic breast cancer. However, its
      mechanism of action has not been fully characterized and appears to be complex.
      This paper reviews current knowledge of the mechanism of action of trastuzumab,
      including HER2 protein downregulation, prevention of HER2-containing heterodimer
      formation, initiation of G1 arrest and induction of p27, prevention of HER2
      cleavage, inhibition of angiogenesis, and induction of immune mechanisms. The
      significance of these mechanisms for selection of concomitant chemotherapy is
      also considered.

PMID- 11521721
TI  - Pharmacologic insights into the future of trastuzumab.
AB  - A combination of factors has been responsible for improvements in cancer survival
      and cure rates. In addition to new therapies with novel/genetic targets, these
      include improvements in drug delivery, new schedules/sequencing of drug
      administration and the identification of combination therapies with greater
      activity/dose density than existing regimens. The recognition that such criteria
      can affect treatment outcome has led to their incorporation into clinical trials
      of new drugs. Furthermore, pharmacokinetic and pharmacodynamic parameters have
      become increasingly important for the rational selection of dose, administration
      route and schedule. The humanized monoclonal antibody trastuzumab (Herceptin) has
      been rationally developed to target the human epidermal growth factor receptor-2
      (HER2), which is overexpressed in 20%-30% of breast cancers and is associated
      with poor prognosis. Trastuzumab when administered i.v. on a weekly schedule
      either alone or in combination with taxanes, improves survival of women with HER2
      positive metastatic breast cancer. Based upon pharmacokinetic considerations,
      current studies are examining whether trastuzumab can be administered i.v. every
      three weeks or by the s.c. route. These regimens would have advantages for
      patients and medical staff in terms of acceptability, ease of administration and,
      potentially, cost effectiveness. Furthermore, various combinations of trastuzumab
      and chemotherapeutic agents are being explored with the aim of identifying the
      optimal combination regimen for clinical use. The rationale for these various
      studies and the studies themselves are described.

PMID- 11521722
TI  - Phase I and II clinical trials of trastuzumab.
AB  - This report summarizes the efficacy of trastuzumab (Herceptin) based on its
      completed clinical trial program in patients with HER2-positive metastatic breast
      cancer for phase I and II studies which have been completed to date and were
      integral in the submission that led to approval of trastuzumab for clinical use
      in the USA. There were three small-scale, phase I clinical trials conducted,
      which were primarily designed to determine the safety and pharmacokinetics of
      trastuzumab (10-500 mg) administered i.v. as single or weekly doses. This was
      followed by two phase II clinical trials of fixed-dose trastuzumab either as a
      single-agent or in combination with cisplatin in 46 and 39 patients, which
      produced overall response rates of 11.6%, and 24.3%, respectively. In a pivotal
      phase II clinical trial, trastuzumab was administered on a bodyweight-adjusted
      basis as a single agent to 222 patients with HER2-positive metastatic breast
      cancer who had relapsed after one or two prior chemotherapy regimens. The overall
      response rate was 21% when assessed in evaluable patients by the investigators
      and 15% when analyzed on an intent-to-treat basis by an independent Response
      Evaluation Committee. The pharmacokinetics of trastuzumab were evaluated in these
      studies and the results are summarized.

PMID- 11521723
TI  - Trastuzumab combined with chemotherapy for the treatment of HER2-positive
      metastatic breast cancer: pivotal trial data.
AB  - A pivotal, randomized, multicenter, phase III trial was conducted to compare
      chemotherapy in combination with trastuzumab (Herceptin) vs. chemotherapy
      (anthracycline plus cyclophosphamide [AC] or paclitaxel) alone as first-line
      treatment for HER2-positive metastatic breast cancer. Results from a total of 469
      patients, randomized to receive either chemotherapy alone or chemotherapy plus
      trastuzumab, revealed that the addition of trastuzumab improved time to disease
      progression significantly (7.6 vs. 4.6 months. P = 0.0001) compared with
      chemotherapy alone. The increase was higher in the trastuzumab plus paclitaxel
      subgroup (6.9 vs. 3.0 months, P = 0.0001) than in the trastuzumab plus AC
      subgroup (8.1 vs. 6.1 months. P = 0.0003). Patients receiving combination therapy
      also had a greater overall response rate (49% vs. 32%, P = 0.0002) and a longer
      median response duration (9.3 vs. 5.9 months, P = 0.0001) than those who received
      chemotherapy alone. Most importantly, median follow-up of 29 months revealed a
      significantly increased median survival in patients receiving trastuzumab plus
      chemotherapy (25.4 vs. 20.3 months, P < 0.025) compared with those receiving
      chemotherapy alone. Trastuzumab plus chemotherapy was well tolerated; adverse
      events were typically mild-to-moderate chills and fever and occurred in
      approximately 40% of patients, primarily following the first administration only.

PMID- 11521724
TI  - Tolerability in patients receiving trastuzumab with or without chemotherapy.
AB  - One of the major expectations from the use of humanized monoclonal antibodies in
      cancer therapy has been that of exploiting the specificity and sensitivity of the
      immune system to achieve selective therapeutic effects devoid of the often severe
      toxicity caused by chemotherapy. The tolerability of trastuzumab (Herceptin) as
      it emerged from the trials where the drug was used as a single agent or in
      combination with chemotherapy largely confirmed that expectation. Adverse events
      most frequently encountered include mild-to-moderate, transient effects related
      to administration of the first dose of trastuzumab. The incidence of severe or
      serious adverse effects attributable to trastuzumab was low. However, the
      occurrence of cardiac toxicity that was unexpectedly high, especially in patients
      previously or concomitantly treated with anthracyclines, could not be predicted
      on the basis of the putative mechanism of action of the antibody. The safety
      profile of trastuzumab is discussed here with a particular focus on
      cardiotoxicity and the issues relating to patient management during trastuzumab
      therapy.

PMID- 11521725
TI  - Ongoing trials with trastuzumab in metastatic breast cancer.
AB  - Following the pivotal clinical trials of trastuzumab (Herceptin), further phase
      II and III studies have been initiated. Preliminary results from a phase II, dose
      response study of single-agent trastuzumab in 113 HER2-positive metastatic breast
      cancer patients without prior chemotherapy for stage IV disease have shown that
      the overall response rate was 23% (six complete responses and 20 partial
      responses), with similar results using both standard- and high-dose regimens of
      trastuzumab. Another phase II study of trastuzumab plus paclitaxel, both given
      weekly, in 63 HER2-positive and -negative patients with metastatic breast cancer
      produced an overall response rate of 62% in HER2-positive and 44% in HER2
      negative patients. A further phase II study is underway to investigate the
      combination of trastuzumab plus docetaxel in 30 HER2-positive patients with
      metastatic breast cancer. Finally, a number of European studies are at an
      advanced stage of planning or are about to start patient recruitment. These
      include docetaxel +/- trastuzumab, aromatase inhibitor +/- trastuzumab, CMF
      (cyclophosphamide, methotrexate, 5-fluorouracil) +/- trastuzumab, vinorelbine +
      trastuzumab, all in HER2-positive patients, and epirubicin-cyclophosphamide (EC)
      + trastuzumab in HER2-positive patients vs. EC alone in HER2-negative patients.
      The results from these trials should be available over the next one to two years.

PMID- 11521726
TI  - Future directions in the adjuvant treatment of breast cancer: the role of
      trastuzumab.
AB  - Current evidence shows that adjuvant cytotoxic or hormonal therapy increases the
      disease-free and overall survival of patients. The analysis by the Early Breast
      Cancer Trialists' Collaborative Group (EBCTCG) showed that
      anthracycline/cyclophosphamide (AC)-containing regimens are more effective than
      those without AC, providing an 11% greater reduction in the risk of death
      compared with non-AC-containing regimens. In addition, paclitaxel and docetaxel
      have significant anti-tumor activity in previously treated patients and
      sequential treatment with paclitaxel may further reduce the risk of recurrence
      and improve survival. Tamoxifen is effective in reducing the risk of recurrence
      and death in patients with estrogen receptor (ER)-positive tumors. The addition
      of tamoxifen to combination chemotherapy in patients with ER-positive tumors
      further reduces the risk of recurrence and improves survival. Debate on the
      effectiveness of tamoxifen in HER2-positive patients is currently underway. A
      number of trials are in progress or planned to investigate the use of the anti
      HER2 monoclonal antibody trastuzumab (Herceptin) in the adjuvant setting. These
      include a National Surgical Adjuvant Breast and Bowel Project (NSABP) adjuvant
      trial (AC --> paclitaxel vs. AC --> paclitaxel + trastuzumab) and an Intergroup
      study (AC --> paclitaxel vs. AC --> paclitaxel + trastuzumab vs. AC -->
      paclitaxel --> trastuzumab). Results from these trials will determine whether
      this novel therapy has a survival benefit in early breast cancer.

PMID- 11521727
TI  - Targeting HER2 in other tumor types.
AB  - The human epidermal growth factor receptor-2 (HER2) is overexpressed/amplified in
      a range of tumor types including breast, ovarian, bladder, salivary gland,
      endometrial, pancreatic and non-small-cell lung cancer (NSCLC). HER2 is
      implicated in disease initiation and progression, associated with poor prognosis,
      and may also predict the response to chemotherapy and hormonal therapy. Anti-HER2
      monoclonal antibodies (MAbs) have been designed to specifically antagonize the
      function of the HER2 receptor in HER2-positive tumors. Clinical phase II and III
      trials have demonstrated the efficacy of the humanized anti-HER2 MAb, trastuzumab
      (Herceptin), both as a single agent and in combination with chemotherapy in HER2
      positive, metastatic breast cancer patients. However, the prevalence of HER2
      overexpression/amplification in various tumor types raises the possibility of
      using anti-HER2 MAbs to antagonize the abnormal function of overexpressed HER2
      receptors in HER2-positive tumors other than breast. Preliminary in vitro studies
      indicate that anti-HER2 MAbs suppress the proliferation of ovarian, gastric and
      NSCLC cell lines that overexpress the HER2 receptor. These results indicate that
      anti-HER2 MAbs may have important therapeutic significance in patients presenting
      with these or other human carcinomas. Clinical trials are either planned or
      underway to assess the therapeutic role of trastuzumab in NSCLC, bladder and
      ovarian cancer.

PMID- 11521728
TI  - Proposed treatment guidelines for HER2-positive metastatic breast cancer in
      Europe.
AB  - The human epidermal growth factor receptor-2 (HER2) is overexpressed/amplified in
      20%-30% of human breast tumors and is a marker for a poor prognosis. For these
      reasons, HER2 has been selected as a therapeutic target for breast cancer
      treatment. Oncologists can no longer ignore the importance of HER2 status for
      treatment algorithms in breast cancer. In light of the consequences of HER2
      status on treatment selection, further research is warranted to refine and
      standardize HER2 testing in order to minimize false-negative results and optimize
      selection of treatment pathways. The anti-HER2 monoclonal antibody (MAb)
      trastuzumab (Herceptin) has proven valuable in treating HER2-positive, advanced
      disease patients. and the availability of this novel biologic agent has important
      implications for clinical practice. This review describes a set of guidelines
      based on the current options for treatment of breast cancer. Two important
      factors have been taken into account in compiling these recommendations: (1) the
      lack of level I evidence to convincingly demonstrate the value of HER2 as a
      predictive marker for resistance or sensitivity to chemo- and hormonal therapy,
      and (2) the recently published pivotal phase II and III trial data proving the
      efficacy of trastuzumab as a single agent and in combination with chemotherapy in
      HER2-positive metastatic breast cancer.

PMID- 11521729
TI  - The role of overexpressed HER2 in transformation.
AB  - The HER family of receptors has an important role in the network of cell signals
      controlling cell growth and differentiation. Although the activity of the HER
      receptor is strictly controlled in normal cells, HER2 receptor overexpression
      plays a pivotal role in transformation and tumorigenesis. HER2 gene amplification
      and/or overexpression of the receptor has been detected in subsets of a wide
      range of human cancers including breast cancer, and is an indicator of poor
      prognosis. It is proposed that overexpressed HER2 in combination with HER3 causes
      high activity of cell-signaling networks, thereby resulting in tumor cell
      proliferation. Thus, the HER2 receptor is an attractive target for new anti
      cancer treatments. Monoclonal antibodies directed against the receptor are the
      most promising of these, and the humanized anti-HER2 monoclonal antibody
      trastuzumab (Herceptin) has shown significant clinical efficacy in clinical
      trials. The anti-tumor mechanisms of anti-HER2 monoclonal antibodies are not
      completely understood. However, some tumor types are not sensitive to
      trastuzumab, suggesting that the response of a tumor to trastuzumab may not only
      be dependent on overexpressed HER2, but may also be influenced by other members
      of the HER receptor family expressed in the tumor cell.

PMID- 11521730
TI  - Trastuzumab in the treatment of advanced breast cancer: single-center experience.
AB  - A significant number of women with advanced breast cancer fail to respond to
      standard-dose chemotherapy. From the beginning of 1999, 17 women with HER2
      positive advanced breast cancer received Herceptin as monotherapy or in
      combination with paclitaxel or other non-anthracyclines. Eight (47%) women
      previously received high-dose chemotherapy followed by haematopoiesis stem cell
      rescue. Three women received Herceptin alone, eleven Herceptin plus paclitaxel
      and three Herceptin and some of the other non-anthracyclines (CCNU, cisplatin and
      gemcitabine). In the group of patients who received Herceptin monotherapy, one
      has partial response (PR), one stable disease (SD) and in the third patient the
      disease progressed. Out of three patients who received Herceptin in combination
      with other non-anthracyclines, two have SD and one progressed. In the group of 11
      women who received Herceptin + Taxol, 7 (64%) patients achieved PR, 2 (18%) SD,
      and 2 (18%) had disease progression. Grade 3-4 neutropenia has been observed in
      four (23%) women. Febrile neutropenia was observed in two cases and resolved
      completely when antibiotics were introduced. Other grade 3 toxicity that has been
      noted is peripheral neuropathy in three (18%) patients, diarrhoea in four (23%)
      and onycholysis in one (6%). Serial heart ultrasound showed no significant
      decline in left ventricular ejection fraction. According to our preliminary
      experience, Herceptin therapy showed promising results in women with metastatic
      breast cancer.

PMID- 11521732
TI  - Hyperinflation: control of functional residual lung capacity.
AB  - Hyperinflation is the consequence of a dysbalance of static forces (determining
      the relaxation volume) and/or of the dynamic components. The relaxation volume is
      determined by an equilibrium between the elastic recoil of the lungs and of the
      chest walls. The dynamic components include the pattern of breathing, upper
      airway resistance and postinspiratory activity of inspiratory muscles. The
      respiratory and laryngeal muscles are under control and thus both static and
      dynamic hyperinflation can be secured. Our knowledge of the mechanism of
      increased FRC is based on clinical observations and on experiments. The most
      frequent stimuli leading to a dynamic increase of functional residual lung
      capacity (FRC) include hypoxia and vagus afferentation. Regulation of FRC is
      still and undetermined concept. The controlled increase of FRC, hyperinflation,
      participates in a number of lung diseases.

PMID- 11521731
TI  - Current use of HER2 tests.
AB  - Reliable detection of HER2 overexpression is important for the success of
      trastuzumab (Herceptin) therapy. Several methods are available for measuring HER2
      expression at the DNA, RNA or protein level. The method most frequently employed
      is immunohistochemical (IHC) detection of the HER2 receptor in paraffin sections.
      Advantages include the precise localization of the HER2 protein, the availability
      of paraffin material and the ease of the procedure. However, IHC can be
      influenced by the sensitivity/specificity of the antibody, tissue treatment and,
      in particular, subjective assessment. These disadvantages do not exist in the
      detection of gene amplification by fluorescence in situ hybridization (FISH) or
      polymerase chain reaction. However, FISH requires expensive equipment that is not
      widely available in pathology laboratories. Another approach quantitates shed
      HER2 antigen in the serum by an enzyme-linked immunosorbent assay. The key
      advantage of this method is the ease of sampling blood, however, serum HER2
      concentrations do not accurately reflect the tumor status. Furthermore, this
      method does not register single-cell expression, which is important for
      therapeutic decision making. For routine diagnostics, the combination of IHC and
      FISH is useful. In addition to improving the accuracy and comparability of HER2
      assays, these optimized protocols may further enhance the efficacy of trastuzumab
      therapy by selecting those patients most likely to respond.

PMID- 11521733
TI  - Hormone metabolism in the pulmonary circulation.
AB  - We measured hormonal levels in blood samples from pulmonary and radial arteries
      in 117 patients undergoing aorto-coronary by-pass surgery with the aim of
      investigating the role of the pulmonary vessel endothelium in hormone metabolism.
      Insulin and glucagon concentrations were significantly higher in pulmonary artery
      blood with respect to radial artery blood (73 +/- 65 vs. 65 +/- 47 pmol/l, p <
      0.005, and 80 +/- 49 vs. 73 +/- 51 ng/l, p < 0.01, respectively), while no
      difference was found for growth hormone, prolactin, C peptide, insulin-like
      growth factor I, follicle stimulating hormone, luteinizing hormone, thyroid
      stimulating hormone, parathyroid hormone, thyroglobulin, triiodothyronine,
      thyroxine, free triiodothyronine, and free thyroxine. Moreover, prolactin
      concentrations were more than twice the normal levels, this being an effect of
      propafol and the opiate fentanyl used for the general anesthesia. Assuming that
      the arteriovenous differences observed are a marker of peptide hormone
      degradation, our study has demonstrated that with similar kinetics insulin and
      glucagon secreted into portal circulation and escaping from hepatic extraction
      undergo further homeostatic removal of about 9-10 % in the pulmonary circulation
      before entering the general circulation.

PMID- 11521734
TI  - Ontogenetic development of energy-supplying enzymes in rat and guinea-pig heart.
AB  - The purpose of the present study was to compare the ontogenetic development of
      the activity of myocardial energy-supplying enzymes in two mammalian species,
      differing significantly in their level of maturation at birth. The animals were
      investigated during the late prenatal period and 2, 7, 14, 21, 25, 30, 63, 120
      and 730 days after birth in the rat and 2, 21, 84 and 175 days in the guinea-pig.
      The following enzymes were assayed in the right and left ventricular myocardium:
      lactate dehydrogenase (LDH, lactate uptake and/or formation), triose phosphate
      dehydrogenase (TPDH, carbohydrate metabolism), glycerol phosphate dehydrogenase
      (GPDH, glycerol-P shuttle)), hexokinase (HK, glucose phosphorylation), malate
      dehydrogenase (MDH, tricarboxylic cycle), citrate synthase (CS, tricarboxylic
      cycle) and hydroxyacyl-CoA dehydrogenase (HOADH, fatty acid breakdown). The rat
      heart, highly immature at birth, exhibits three different developmental patterns
      of energy-supplying enzymes, identical in both ventricles: (i) two mitochondrial
      enzymes of aerobic metabolism (CS, HOADH) and GPDH have a relatively low activity
      at the end of prenatal life; thereafter their activity steadily increases,
      approaching the adult levels between the 3rd and 4th postnatal weeks. A
      significant decrease was observed between the 4th and 24th months. (ii) MDH and
      LDH: prenatal values were significantly higher as compared with the 2nd postnatal
      day; after this period the activities increased up to adulthood (4 months) and
      decreased during senescence. (iii) The activities of HK and TPDH are
      characterized by only moderate changes during development. HK differs from all
      other enzymes by the highest prenatal values, which exceed even adult values. In
      contradiction to the rat heart, the developmental differences in more mature
      guinea-pig heart were significantly less pronounced. The only ontogenetic
      differences observed were the lower activities of enzymes connected with aerobic
      metabolism at the end of the prenatal period. Our results point to possible
      differences in the development of adaptive metabolic pathways in animals with
      different levels of maturation at birth.

PMID- 11521735
TI  - Dispersion of cell-to-cell uncoupling precedes low K+-induced ventricular
      fibrillation.
AB  - We hypothesize that hypokalemia-related electrolyte imbalance linked with
      abnormal elevation of intracellular free Ca2+ concentration can cause metabolic
      disturbances and subcellular alterations resulting in intercellular uncoupling,
      which favor the occurrence of malignant arrhythmias. Langendorff-perfused guinea
      pig heart (n = 44) was subjected to a standard Tyrode solution (2.8 mmol/l K+)
      followed by a K+-deficient solution (1.4 mmol/l K+). Bipolar ECG of the left
      atria and ventricle was continuously monitored and the incidence of ventricular
      fibrillation was evaluated. Myocardial tissue sampling was performed during
      stabilization, hypokalemia and at the onset of fibrillation. Enzyme activities of
      succinic dehydrogenase, glycogen phosphorylase and 5-nucleotidase were determined
      using in situ catalytic histochemistry. The main gap junction protein, connexin
      43, was labeled using mouse monoclonal antibody and FITC conjugated goat
      antimouse antibody. Ultrastructure was examined by transmission electron
      microscopy. The free Ca2+ concentration was measured by the indo-1 method in
      ventricular cell cultures exposed to a K+-free medium. The results showed that
      sustained ventricular fibrillation appeared within 15-30 min of low K+ perfusion.
      This was preceded by ectopic activity, episodes of bigeminy and tachycardia.
      Hypokalemia induced moderate reversible and sporadically irreversible subcellular
      alterations of cardiomyocytes and impairment of intercellular junctions, which
      were heterogeneously distributed throughout myocardium. Patchy areas with
      decreased enzyme activities and diminished immunoreactivity of connexin-43 were
      found. Furthermore, lack of external K+ was accompanied by an increase of
      intracellular Ca2+. The prevention of Ca2+ overload by either 1 mmol/l Ni2+
      (Na+/Ca2+ inhibitor), 2.5 micromol/l verapamil, 10 micromol/l d-sotalol or 10
      micromol/l tedisamil was associated with the protection against fibrillation. The
      results indicate that hypokalemia induces Ca2+ overload injury and disturbances
      in intercellular coupling. Dispersion of these changes throughout the myocardium
      may serve as the basis for microreentry circuits and thus favor fibrillation
      occurrence.

PMID- 11521736
TI  - A comparison of the effects of troglitazone and vitamin E on the fatty acid
      composition of serum phospholipids in an experimental model of insulin
      resistance.
AB  - The aim of this study was to investigate the effects of troglitazone (TRO)--a new
      insulin-sensitizing agent--on some metabolic parameters in an experimental model
      of hypertriglyceridemia and insulin resistance, hereditary hypertriglyceridemic
      rats, and to compare its effects with those of vitamin E, an antioxidant agent.
      Three groups of the above rats were fed diets with a high content of sucrose (70%
      of energy as sucrose) for four weeks. The first group was supplemented with TRO
      (120 mg/kg diet), the second one with vitamin E (500 mg/kg diet), and the third
      group served as the control. Vitamin E supplementation did not lower serum
      triglycerides (2.42 +/- 0.41 vs. 3.39 +/- 0.37 mmol/l, N.S.) while TRO did (1.87
      +/- 0.24 vs. 3.39 +/- 0.37 mmol/l, p < 0.01). Neither TRO nor vitamin E
      influenced the serum levels of free fatty acids (FFA). Both drugs influenced the
      spectrum of fatty acids in serum phospholipids--TRO increased the levels of
      polyunsaturated fatty acids (PUFA) n-6 (36.04 +/- 1.61 vs. 19.65 +/- 1.56 mol %,
      p < 0.001), vitamin E increased the levels of PUFA n-3 (13.3 +/- 0.87 vs. 6.79 +/
      0.87 mol %, p < 0.001) and decreased the levels of saturated fatty acids (32.97
      +/- 0.58 vs. 51.45 +/- 4.01 mol %, p < 0.01). In conclusion, TRO lowered the
      level of serum triglycerides but vitamin E did not have this effect in
      hypertriglyceridemic rats. Compared with TRO, vitamin E had a different effect on
      the spectrum of fatty acids in serum phospholipids.

PMID- 11521737
TI  - The effects of hyperoxia, hypoxia, and ischemia/reperfusion on the activity of
      cytochrome oxidase from the rat retina.
AB  - Cytochrome oxidase activity from the retina can be enhanced or depressed by free
      radical-mediated reactions both in positive and negative aspect. The greatest
      effect was exerted by ischemia/reperfusion, which significantly increased the
      fluorescent products of lipid peroxidation (358 %, P < 0.01) and inhibited the
      enzyme activity (14%, P < 0.001). After hyperoxia the fluorescent products
      slightly increased (192%, P < 0.05) as well as the enzyme activity (133 %, P <
      0.05). Hypoxia had no effect on any of these parameters. Specific changes in the
      composition of fluorophores after ischemia/reperfusion were revealed in the
      fluorescence spectra. The fact that increased lipid peroxidation after hyperoxia
      and after ischemia/reperfusion does not produce the same effect upon cytochrome
      oxidase activity might be explained by changes in the kinetic behavior of
      cytochrome oxidase. In the control enzyme preparation, two binding sites for
      cytochrome c were observed. One was of the low-affinity (Km = 60 microM) and the
      other of the high-affinity (Km = 1.12 microM). After in vitro-initiated lipid
      peroxidation, the low-affinity binding site was lost and the activity measured
      under "optimum" conditions at a single cytochrome concentration was higher than
      in the controls. This implies that oxidative damage to cytochrome oxidase in vivo
      can be site-specific and its extent should be estimated by performing detailed
      kinetic analysis as otherwise the results might be misleading.

PMID- 11521738
TI  - Detection of estrogenicity by bioassay on the mouse mammary gland in vivo.
AB  - The wide chemical diversity of estrogenic compounds precludes an accurate
      prediction of estrogenic activity on the basis of chemical structure or
      radioimmunological assay and thus requires that the potency of these compounds is
      defined by bioassay. The mammary duct growth response in intact prepubertal and
      adult gonadectomized female and male mice of the C3H/Di strain was used to assess
      the estrogenicity of synthetic compounds or their derivatives. The vehicle for
      tested compounds should be free of estrogenic and other hormonal effects. Olive
      oil or sunflower oil exerted estrogenic activities and were thus unsuitable as
      vehicles for the tested compounds. The absence of estrogenic activity, high
      solubility of different steroid hormones, and the low incidence of the
      inflammatory reactions at the injection site were achieved by using a vehicle
      containing benzyl alcohol, benzyl benzoate, butylhydroxyanisole,
      butylhydroxytoluene, ethyl oleate and ethanol. The bioassay was primarily
      designed to examine the effect of tested compounds on mammogenesis. The duration
      of hormone treatment was chosen to be long enough for induction of duct growth
      but too short to induce lobuloalveolar differentiation. Females were treated for
      10 days, males for 15 days. The proportional volume occupied by mammary
      epithelial structures was estimated by the modified Chalkley's technique. The
      mean coefficient of variation of quantitative evaluation of 10 different mammary
      glands obtained by two operators varied between 3.2 and 17.4%. The mean
      coefficient of variation of quintuplicate determinations of each mammary gland by
      one operator was 10.1%, and 11.1% by the other. The correlation coefficient
      between results of two operators was 0.994. Estrogens are primarily defined by
      their ability to increase the mitotic activity of female secondary sex organs.
      However, our results have shown that progesterone alone, if administered in a
      high dose, stimulates mammary growth in both intact prepubertal and OV-X female
      mice similarly as the synthetic progestatial steroid norethindrone with inherent
      estrogenic properties. In contrast, progesterone alone had no effect, in young
      intact or adult castrated males, but norethindrone did stimulate mammary growth.
      These results demonstrated that the mammary gland of males is a suitable model
      for estrogen screening.

PMID- 11521739
TI  - The effect of 5'-(N,N-dimethyl)-amiloride on cytotoxic activity of doxorubicin
      and vincristine in CEM cell lines.
AB  - Intracellular pH (pHi) plays an important role in anticancer drug accumulation in
      cancer cells. Resistant cells often express membrane P-glycoprotein responsible
      for active drug extrusion and participating in increased pHi. In the present
      paper, we report on the influence of Na+/H+-exchanger inhibitor, 5'-(N,N
      dimethyl)-amiloride (AMI), on the cytotoxic effects of doxorubicin (DOXO) and
      vincristine (VCR) in the parental CEM, and resistant CEM/DNR and CEM/VCR cell
      lines. The obtained results revealed a potentiating effect of AMI to both
      anticancer drugs in parental CEM line. However, AMI did not significantly
      potentiate the effect of DOXO or VCR in resistant CEM cell lines. We conclude,
      that inhibition of Na+/H+-exchanger by AMI is not sufficient for reversal of drug
      resistance in the tested CEM/DNR and CEM/VCR cell lines and the possible change
      in pHi does not affect the mechanisms of cell resistance.

PMID- 11521740
TI  - The activity of antioxidant enzymes and the content of uncoupling protein-1 in
      the brown adipose tissue of hypothyroid rats: comparison with effects of iopanoic
      acid.
AB  - The activity of antioxidant enzymes, copper-zinc superoxide dismutase (CuZnSOD),
      manganese superoxide dismutase (MnSOD) and catalase (CAT), as well as that of the
      mitochondrial FAD-dependent alpha-glycerophosphate dehydrogenase (alpha-GPD) in
      the rat interscapular brown adipose tissue (IBAT) were studied after the
      treatment with methimazole (MMI) for three weeks or with iopanoic acid (IOP) for
      five days. Besides, the mitochondrial concentration of uncoupling protein-1 (UCP
      1) and the activity of catecholamine degrading enzyme monoamine oxidase (MAO) in
      the IBAT as well as the activity of the catecholamine synthesizing enzyme,
      dopamine beta-hydroxylase (DBH) in rat serum were examined. Judging by the
      significantly enhanced level of serum DBH, which is an index of sympathetic
      activity, and that of IBAT MAO, the increase in MnSOD and CAT activities in the
      IBAT of hypothyroid (MMI-treated) rats seems to be due to elevated activity of
      sympathetic nervous system (SNS). However, CuZnSOD activity is not affected by
      SNS. On the contrary, IOP, which is a potent inhibitor of T4 deiodination into T3
      producing "local" hypothyroidism, did not change either SNS activity or
      activities of IBAT antioxidant enzyme. However, both treatments significantly
      decreased IBAT UCP-1 content and alpha-GPD activity suggesting that the optimal
      T3 concentration in the IBAT is necessary for maintaining basal levels of these
      key mitochondrial parameters.

PMID- 11521741
TI  - Changes of gastric lipase activity after ethanol and indomethacin administration:
      influence of pretreatment with allopurinol, pentoxifylline and L-DOPA.
AB  - Gastric lipase (GL) plays an important role in emulsification and digestion of
      food fat. Lipids are components of the hydrophobic mucus and mucosa barrier.
      Damage of the gastric mucosa may therefore be related to changes in the lipid
      content and GL activity. In the present paper, we studied the effect of
      administration of a single dose of 96 % ethanol (E) and indomethacin 20 mg x kg(
      1) (IND) on the activity of GL and on the concentrations of nonesterified fatty
      acids (NEFA) and triacylglycerols (TG) in the gastric mucosa of rats.
      Furthermore, we studied how these changes are affected by allopurinol (ALO),
      pentoxifylline (PX) and L-DOPA pretreatment 30 min before administration of E or
      IND. The effect of sialoadenectomy (SA) on these parameters was also evaluated.
      We found: 1) significant (p < 0.01) inhibition of GL activity after
      administration of E and IND and also ALO, as well as after pretreatment with ALO
      before E and PX before IND. L-DOPA administered alone stimulated GL activity, but
      its administration before IND significantly (p < 0.01) inhibited this enzymatic
      activity. GL activity was decreased to the threshold values in SA rats and after
      administration of E to SA animals. 2) NEFA concentrations were decreased after E
      and increased significantly (p < 0.01) after IND administration. A marked
      significant (p < 0.01) decrease in NEFA was found after PX and L-DOPA
      administration. The administration of ALO also lowered the concentration of NEFA.
      Pretreatment by drugs before E and IND resulted in a significant increase of NEFA
      in comparison with the drugs given alone (p < 0.05 for ALO + E; p < 0.01 for PX +
      IND). 3) TG were also decreased in all experimental groups in comparison with the
      control group, i.e. after E and IND, after ALO and SA and also after pretreatment
      by ALO before E. The concentration of TG decreased after PX, significantly (p <
      0.05) after L-DOPA and after pretreatment by PX before IND. Pretreatment by ALO
      before E and L-DOPA before IND resulted in the increase of TG in comparison with
      drugs alone. Thus, these results suggest certain protective effect of
      pretreatment with ALO, PX and L-DOPA against the E- and IND-induced decrease in
      NEFA and TG during injury of the gastric mucosa. On the other hand, inhibition of
      GL activity was also apparent after administration of these drugs before E and
      IND, which suggest presence of a persisting impairment of lipid digestion in the
      stomach.

PMID- 11521742
TI  - The osmotic component of ethanol and urea action is critical for their immediate
      stimulation of thyrotropin-releasing hormone (TRH) release from rat brain septum.
AB  - There is considerable evidence linking alcohol consumption and sedation and TRH
      in the brain septum. Moreover, innate septal TRH concentration is inversely
      related to the degree of ethanol preference. Recently we demonstrated in rats
      that four-week ethanol drinking increased the septal TRH content by 50 %. We had
      shown previously that ethanol induces neuronal swelling, which is known to evoke
      the secretion of hormones, peptides and amino acids from various types of cells.
      We have therefore explored the effect of hyposmotic medium and of 80 and 160 mM
      ethanol and 80 mM urea (both permeant molecules) in isosmotic and hyperosmotic
      (preventing cell swelling) media on the in vitro release of TRH by the rat
      septum. Lowering medium osmolarity resulted in a hyposmolarity-related increase
      in TRH secretion. Both ethanol and urea stimulated TRH release only in isosmolar
      solution. Our data indicate that ethanol in clinically relevant concentrations
      can induce TRH release from the septum by a mechanism involving neuronal
      swelling.

PMID- 11521743
TI  - Postnatal development of energy metabolism in the rat brain.
AB  - The activities of cytochrome c oxidase and F0F1-ATPase as well as the content of
      cytochromes cc1, aa3, and b were investigated in free brain mitochondria in the
      course of postnatal development and aging. The results show an increase of Vmax
      of both enzymes during postnatal development (between day 5 and 30). During the
      following phase ending at the age of 6 months, a decrease of F0F1-ATPase and
      cytochrome c oxidase activity occurs. From 6 to 12 months of age the activity of
      these enzymes did not change. The KM for both enzymes remained unchanged during
      the whole period observed. The content of cytochromes increased from the low
      values found in young rats, reached the highest values at around one month, and
      decreased till the age of 3 months. Later, their content in brain mitochondria
      did not markedly change. Our results suggest that the metabolic maturation of
      brain mitochondria differs in several aspects from the same process in other
      tissues, mainly in the time course. This is probably due to the unique role of
      neural tissue in the organism.

PMID- 11521744
TI  - Ibotenate lesion of the ventromedial hypothalamus lowers hyperthermic effects of
      prostaglandin E1.
AB  - This experiment tested the effects of an intracerebroventricular injection of
      prostaglandin E1 on the sympathetic activation and the thermogenic changes in
      rats with ibotenate lesions of the ventromedial hypothalamus. Under pentobarbital
      anesthesia, twelve Sprague-Dawley male rats were lesioned bilaterally in the
      ventromedial hypothalamus with an injection of ibotenic acid (30 nmol into each
      side). Sham lesions were carried out in other twelve control rats. After 48 h,
      all animals were anesthetized with ethyl-urethane. The firing rate of the
      sympathetic nerves innervating the interscapular brown adipose tissue and the
      colonic and interscapular brown adipose tissue temperatures were monitored before
      and after an intracerebroventricular injection of prostaglandin E1 (500 ng) or
      saline. Prostaglandin E1 induced an increase in the firing rate of sympathetic
      nerves and the colonic and interscapular brown adipose tissue temperatures. These
      effects were reduced by the ventromedial hypothalamic lesion. Since ibotenic acid
      destroys cell bodies, the findings indicate that neurons of the ventromedial
      hypothalamus play a considerable role in the control of sympathetic activation
      and the thermogenic changes during prostaglandin E1 hyperthermia.

PMID- 11521745
TI  - Ventilatory response to sustained hypoxia in carotid body denervated rats.
AB  - Hypoxia stimulates ventilation, but when it is sustained, a decline in the
      ventilatory response is seen. The mechanism responsible for this decline lies
      within the CNS, but still remains unknown. In this study, we attempted to
      elucidate the possible role of hypoxia-induced depression of respiratory neurons
      by comparing the ventilatory response to hypoxia in intact rats and those with
      denervated carotid bodies. A whole-body plethysmograph was used to measure tidal
      volume, frequency of breathing and minute ventilation (VE) in awake and
      anesthetized intact rats and rats after carotid body denervation during exposure
      to hypoxia (FIO2 0.1). Fifteen-minute hypoxia induced an initial increase of VE
      in intact rats (to 248% of control ventilation in awake and to 227% in
      anesthetized rats) followed by a consistent decline (to 207% and 196% of control
      VE, respectively). Rats with denervated carotid bodies responded with a smaller
      increase in VE (to 134% in awake and 114% in anesthetized animals), but without a
      secondary decline (145% and 129% of control VE in the 15th min of hypoxia). These
      results suggest that afferentation from the carotid bodies and/or the substantial
      increase in ventilation are crucial for the biphasicity of the ventilatory
      response to sustained hypoxia and that a central hypoxic depression cannot fully
      explain the secondary decline in VE.

PMID- 11521746
TI  - Activation of mitochondrial glycerophosphate cytochrome c reductase in
      regenerating rat liver by triiodothyronine.
AB  - Triiodothyronine administration before partial hepatectomy increased the activity
      of mitochondrial glycerophosphate cytochrome c reductase. The enzyme activity was
      further activated after partial hepatectomy during the regenerative process. Our
      findings showed that: a) the increase of glycerophosphate cytochrome c reductase
      induced by triiodothyronine was further potentiated by the regeneration process,
      b) the high activity of the glycerophosphate shuttle was maintained after partial
      hepatectomy during the period, when most of the liver tissue had again been
      recovered.

PMID- 11521747
TI  - Why do asthmatic subjects respond so strongly to inhaled adenosine?
AB  - Bronchospasm induced by adenosine is blocked by representatives of all the major
      classes of drugs used in the treatment of asthma. Understanding the mechanism of
      this bronchospasm may help understand the way these drugs work. Clinical studies
      have suggested involvement of neural pathways, mast-like cells and mediators such
      as histamine, serotonin and lipoxygenase products. There is a strong link between
      responsiveness to adenosine and eosinophilia. In different animal models A1, A2b
      and A3 adenosine receptor subclasses have all been implicated in inducing
      bronchospasm. whilst occupation of the A2a receptor generally has no, or the
      opposite effect. At least two different mechanisms, both involving neural
      pathways, exist. One, involving the adenosine A1 receptor, functions in mast cell
      depleted animals; the other requires interaction with a population of mast-like
      cells activated over A2b or A3 receptors. Not only histamine but also serotonin
      and lipoxygenase products released from the mast-like cells are potential
      mediators. In animal models good reactivity to adenosine receptor agonists is
      generally only found when the animals are first sensitized and exposed to
      allergen in ways likely to induce an allergic inflammation. An exception is the
      BDE rat, which reacts to adenosine receptor agonists such as APNEA or NECA even
      without allergen exposure. This rat strain does however show evidence of
      spontaneous eosinophilic inflammation in the lung even without immunization. As
      mast cells both release adenosine and respond to adenosine, adenosine provides a
      non-specific method of amplifying specific signals resulting from IgE/antigen
      interaction. This mechanism may not only have a pathological significance in
      asthma; it may be part of a normal bodily defense response that in asthmatic
      subjects is inappropriately activated.

PMID- 11521748
TI  - Involvement of corticotropin-releasing factor subtype 1 receptor in the
      acquisition phase of learned helplessness in rats.
AB  - To determine if CRF receptor subtype 1 (CRF1) is involved in the acquisition
      phase of LH, we administered CRF receptor antagonists, CRA 1000 and CP-154,526,
      60 min before (acquisition phase) or immediately after (consolidation phase)
      inescapable shocks on day 1, and 60 min before (retention phase) escape test on
      day 2. CRA1000 (10 mg/kg. p.o.) and CP-154,526 (30 mg/kg, p.o.) decreased the
      number of escape failures in the acquisition phase, but not in consolidation and
      retention phases. The tricyclic antidepressant, imipramine did not affect the
      number of escape failures in all 3 phases. Thus, the CRF1 receptor is apparently
      involved in the resultant escape failures in the acquisition phase of LH in rats.

PMID- 11521749
TI  - Increased kynurenic acid in the brain after neonatal asphyxia.
AB  - In the brain, L-kynurenine is an intermediate for the formation of kynurenic
      acid, a metabolite with neuroprotective activities, and a substrate for the
      synthesis of 3-hydroxy-kynurenine, a metabolite with neurotoxic properties. In
      the present study, alterations of L-kynurenine, 3-hydroxy-kynurenine and
      kynurenic acid levels were examined in the brain of neonatal (10 minutes old)
      rats after 5, 10, 15 or 20 minutes of asphyxia, and in the brain of the
      corresponding caesarean-delivered controls, using sensitive high-performance
      liquid chromatographic methods. Among kynurenines we found a marked time
      dependent increase of kynurenic acid levels, a moderately delayed increase of 3
      hydroxy-kynurenine, and a trend for a decrease of L-kynurenine content. Thus, the
      brain reacted rapidly to the oxygen deficit by increasing kynurenic acid levels
      by 44% already after 5 minutes of asphyxia, and the most prominent elevation of
      kynurenic acid (302% of control) was found after 20 minutes of asphyxia--the
      critical time limit of survival.

PMID- 11521750
TI  - Extended treatment with typical and atypical antipsychotic drugs differential
      effects on the densities of dopamine D2-like and GABAA receptors in rat striatum.
AB  - In situ radioligand binding and quantitative autoradiography have been used to
      measure the density of striatal D1-like, D2-like, and GABAA receptors in rats
      treated with haloperidol at 0.01 or 0.1 mg/kg/ day or chlorpromazine, olanzapine
      or clozapine at 0.1 or 1.0 mg/kg/day for 1, 3 or 7 months. [3H]SCH23390 binding
      to D1-like receptors was not changed by any drug treatments. There were
      significant increases in [3H]nemonapride binding to D2-like receptors at
      different time points due to treatment with haloperidol, chlorpromazine and
      olanzapine. By contrast, treatment with clozapine and olanzapine caused a time
      dependent decrease in [3H]muscimol binding to the GABAA receptor. These data
      suggest that treatment with atypical antipsychotic drugs, but not typical
      antipsychotic drugs, affect striatal GABAergic neurons. In addition, it would
      appear that clozapine might be unique in that it does not increase dopamine-D2
      like receptor density at doses which would be predicted to have antipsychotic
      effects in humans. The extent to which such changes are involved in the
      therapeutic effects of drugs such as olanzapine and clozapine remains to be
      determined.

PMID- 11521751
TI  - Humic acid induced growth retardation in a sertoli cell line, TM4.
AB  - Humic acid (HA) is a fluorescent deep brown organic, polymeric compound composed
      of phenolic acid. Intraperitoneal injection of HA in rats induced testicular
      morphological changes including degeneration of the seminiferous tubule,
      reduction in the number of Sertoli cells and spermatogonia, and a loss of
      spermatids. It was suggested that Sertoli cells may be involved in the
      progression of testicular atrophy. In this study, we used a mouse Sertoli cell
      Line, TM4, to investigate the effect of HA on Sertoli cells and the mechanism of
      the testicular atrophy induced by HA. We found that the cell growth of TM4 cells
      were reduced in 1 to 4 days of HA exposure. FACScan analysis of the DNA content
      of HA-treated TM4 cells revealed that there was no sub-G1 peak, indicating that
      the TM4 cells did not commit to the programmed cell death. However, a large
      proportion of TM4 cells were arrested at the G1 phase. The percentage of TM4
      cells at the G1 phase increased from 36% to 84% after HA treatment for 4 days.
      Western blot assay of HA-treated TM4 cells showed that the expression of cyclin
      D1 protein decreased while the expression of p27kiP1 protein increased. These
      results suggest that HA-induced testicular atrophy is linked in part to an
      inhibitory effect on the growth of Sertoli cells. This model may be useful in
      investigation of environmental agents inducing testicular atrophy.

PMID- 11521752
TI  - The potency of acyclovir can be markedly different in different cell types.
AB  - Acyclovir is an acyclic guanine analog with a considerable activity against
      herpes simplex viruses. We studied the antiherpetic activity of acyclovir in
      macrophages and fibroblast cell lines. Utilising a plaque reduction assay we
      found that acyclovir potently inhibited the HSV-1 replication in macrophages
      (EC50) = 0.0025 microM) compared to Vero (EC50 = 8.5 microM) and MRC-5 (EC50 =
      3.3 microM) cells. The cytotoxicity of acyclovir was not detected at
      concentrations < or = 20 microM, thus the selective index in macrophages was
      >8000. This marked difference in antiherpetic activity between macrophages and
      fibroblasts was not observed with Foscarnet and PMEA. We suggest that this potent
      antiviral effect of acyclovir is mainly due to a proficient phosphorylation of
      the drug and/or a favourable dGTP/acyclovir triphosphate ratio in macrophage
      cells.

PMID- 11521753
TI  - Induction of metallothionein in the livers of female Sprague-Dawley rats treated
      with 2,3,7 ,8-tetrachlorodibenzo-p-dioxin.
AB  - Metallothioneins (MTs) are cysteine-rich metal-binding proteins that exert
      cytoprotective effects against metal toxicity and external stimuli including
      ionizing or ultraviolet B irradiation. Since 2,3,7,8-tetrachlorodibenzo-p-dioxin
      (TCDD) is known to cause an exaggerated oxidative stress response in animals and
      in different organs, we have studied possible involvement of MT in the oxidative
      responses induced by TCDD. Female Sprague-Dawley (SD) rats (6-week old) were
      administered a single oral dose of TCDD that varied from 1.0 to 4.0 microg/kg
      body weight. The serum and tissues were collected 7 days after dosing. Indicators
      of oxidative damage were assessed. Significant increases in serum 8
      hydroxydeoxyguanosine (8-OHdG) levels were observed in the rats dosed with 2.0
      and 4.0 microg TCDD/kg bw. Only 4.0 microg TCDD/kg bw produced a decrease in
      reduced glutathione concentration in the liver. Immunohistochemical staining
      revealed a TCDD-induced increase in heme oxygenase-1 (HO-1) expression in the
      hepatic macrophages (Kupffer cells). Under these conditions, MT protein as well
      as the mRNAs of MT-I and MT-II, were dose-dependently induced in the liver by
      TCDD doses from 1.0 microg/kg bw. TCDD-induced MT was found to localize in the
      parenchymal cells of the liver. Serum concentrations of cytokines (TNF-alpha, IL
      1beta and IL-6) were not affected by TCDD. The hepatic concentrations of Cu, Zn
      and Fe were all increased significantly by TCDD administration. Our results
      suggest that MT levels are increased in the liver upon exposure to TCDD, perhaps
      by TCDD-generated reactive oxygen species, and that it may play a protective role
      in TCDD-induced oxidative stress responses as an antioxidant.

PMID- 11521754
TI  - Regional differences in peptide degradation by rat cerebral microvessels: a
      potential novel regulatory mechanism for communication between blood and brain.
AB  - The blood-brain barrier (BBB), composed of the microvessels of cerebral capillary
      endothelial cells, regulates the passage of peptides into the brain in several
      ways, mainly by saturable transport or passive diffusion. Here we describe an
      additional mechanism by which this regulatory function can occur. Cerebral
      microvessels were isolated from different regions of the brain and incubated with
      the mu-opiate selective endomorphin-1 (Tyr-Pro-Trp-Phe-NH2) or the opiate
      modulating Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2), both tetrapeptides selectively
      tritiated at the Pro. Degradation was determined by HPLC. For both peptides, the
      metabolism by microvessels from the cerebral cortex was much greater than that by
      microvessels from the hypothalamus or pons. For endomorphin-1, the least
      degradation was in the pons; for Tyr-MIF-1 there was no difference in metabolism
      by microvessels from the pons or hypothalamus. The results show a novel mechanism
      at the BBB by which the BBB can selectively regulate the activity of different
      peptides in different regions of the brain.

PMID- 11521755
TI  - The depressor effect of nitroglycerin is mediated by calcitonin gene-related
      peptide.
AB  - Previous investigations have suggested that vasodilator responses to
      nitroglycerin involve in stimulation of calcitonin gene-related peptide (CGRP)
      release. Therefore, we tested whether depressor effect of nitroglycerin is
      mediated by CGRP. A catheter was inserted into the left femoral artery to record
      blood pressure and drugs were administered through cannulae inserted into the
      right femoral vein. Nitroglycerin (15, 30, 60, 120 and 150 microg/kg) caused
      depressor effects in a dose-dependent manner. Nitroglycerin (30 or 150 microg/kg)
      caused a depressor effect with an increase in plasma concentrations of CGRP. The
      effects of nitroglycerin were significantly attenuated by methylene blue, an
      inhibitor of guanylate cyclase, or by pretreatment with capsaicin (50 mg x kg(
      1), s.c.), which depletes neurotransmitters in sensory nerves. The present study
      suggests that the depressor effect of nitroglycerin is related to stimulation of
      CGRP release in the rat.

PMID- 11521756
TI  - Bullatacin, a potent antitumor annonaceous acetogenin, inhibits proliferation of
      human hepatocarcinoma cell line 2.2.15 by apoptosis induction.
AB  - Bullatacin, isolated from the fruit of Annona atemoya, is one of the most
      potentially effective antitumor annonaceous acetogenins. Bullatacin was studied
      here for its ability to inhibit the proliferation of 2.2.15 cells, hepatitis B
      virus (HBV) DNA transfected human hepatocarcinoma cell line. It was found that
      bullatacin induced cytotoxicity of 2.2.15 cells in a time- and dose-dependent
      manner. Fifty percent effective dose (ED50) on day 1 of exposure to bullatacin
      were 7.8 +/- 2.5 nM for 2.2.15 cells. [3H]-Thymidine incorporation assays showed
      almost the same results. Bullatacin-treatment also reduced concentrations of
      hepatitis B surface antigen (HBsAg) in the cultured medium released from 2.2.15
      cells, coincident with the decrease in the cell proliferation. Analysis of
      mophological changes of bullatacin-treated 2.2.15 by inverted phase-contrast
      microscope and eletron microscopy revealed a possible model of action for
      bullatacin to inhibit proliferation of 2.2.15 cells by inducing apoptosis. Most
      of the bullatacin-induced cell death was found to be due to apoptosis, as
      determined by double staining with fluorescein-isothiocyanate (FITC)-labeled
      annexin V and propidium iodide (PI).

PMID- 11521757
TI  - Endogenous nitric oxide inhibits neutrophil adherence to lung epithelial cells to
      modulate interleukin-8 release.
AB  - To investigate the effect of neutrophil adherence to epithelial cells on the
      release of interleukin 8 (IL-8), we measured neutrophil adherence in the presence
      or absence of IFN-gamma+TNF-alpha+IL-1beta (cytomix) stimulation on cultured A549
      epithelial cells. The extent of neutrophil adherence to A549 epithelial cells was
      measured and the concomitant production of IL-8 and nitrite were assayed. The
      roles of adhesion molecules and nitrite in modulation of neutrophil adherence
      were examined by pretreatment with oversaturating ICAM-1 blocking antibody and L
      NAME (1 mM), respectively. There was a time-dependent spontaneous and cytomix
      induced release of IL-8 from epithelial cells, as well as a time-dependent
      increase in the magnitude of neutrophil adherence to epithelial cells.
      Stimulation of epithelial cells with cytomix induced a further increase in
      neutrophil adherence. Pretreatment with oversaturated ICAM-1 monoclonal antibody
      inhibited neutrophil adherence with or without cytomix stimulation. The
      inhibition of neutrophil adherence to epithelial cells with ICAM-1 monoclonal
      antibody or a semipermeable membrane downregulated the release of IL-8 with or
      without cytomix stimulation. Stimulation with cytomix decreased nitrite
      production. Both neutrophil adherence and L-NAME pretreatment significantly
      inhibited the production of nitrite. The inhibition of neutrophil adherence to
      epithelial cells with ICAM-1 monoclonal antibody or a semipermeable membrane
      upregulated nitrite production. Pretreatment with L-NAME failed to modify the
      spontaneous release of IL-8, but significantly enhanced the response to adherence
      and cytomix. In conclusion, endogenous nitric oxide may play a role in preventing
      neutrophil adherence to lung epithelial cells, thus modulating concomitant IL-8
      release.

PMID- 11521758
TI  - New joints for the Millennium: wear control in total replacement hip joints.
AB  - Hip joint replacement is described as the greatest achievement in orthopaedic
      surgery in the twentieth century. The field has been dominated for some forty
      years by implants based upon metallic femoral heads and stems and polymeric
      acetabular cups. At the dawn of the new Millennium, many alternative materials
      and designs are now being proposed or evaluated. The reasons for these
      developments and the current contributions of engineering science and tribology
      to advances in hip replacement are discussed. Illustrations are presented of the
      significant changes being proposed or introduced. While the new designs of total
      hip replacements offer exciting engineering contributions to the future of joint
      replacement, the long-term benefits to patients will depend upon the biological
      response to the new devices.

PMID- 11521759
TI  - Some failure modes of four clinical bone cements.
AB  - The fracture or failure behaviours of four commercial acrylic-based bone cements
      have been examined in tensile, bending and compression modes, and their
      mechanical properties are reviewed. It was found that Palacos R-40 bone cement
      had high radiopaque agent concentration, with high surface hardness. It exhibited
      a much lower bending strength and bending modulus compared with the other three
      bone cements (CMW1, CMW2000 and Simplex P). The textures of tensile fracture
      surfaces produced were similar for the four bone cements studied. The fracture
      surface was fragmented by crevices, which developed through the matrix and around
      large undissolved polymethylmethacrylate (PMMA) beads. Three bands with different
      features existed on the bending fracture surfaces, with an abrupt transition
      between them. It appears that the agglomerates of zirconium dioxide particles are
      implicated in Palacos R-40 bone cement fracture surface. The examination of
      compressive failed specimens revealed that a 'yielded crack band' existed across
      the transverse section. Plastic deformation resulted in the PMMA beads being
      squashed in the longitudinal direction and dilated in the transverse direction.

PMID- 11521760
TI  - Polymerization shrinkage of dental composite resins.
AB  - Aesthetic materials have always been a priority for the restoration of anterior
      teeth; increasingly, they have also gained prominence in the restoration of
      posterior teeth. This has been due to their advantages as an alternative to
      amalgam. Their drawbacks however, can include poor marginal adaptation,
      postoperative sensitivity and cuspal movement. These are particularly associated
      with the polymerization shrinkage accompanying the placement of composite resins.
      Consequently, a variety of methods have been used for determining the
      polymerization shrinkage. These range from dilatometer methods, specific gravity
      methods and deflecting disc systems to optical methods. In this work a unique
      method for the qualitative analysis of polymerization shrinkage was undertaken.
      This method utilized a miniature transducer and provided details of the shrinkage
      from within the material. The results indicated movement of material towards the
      initiating light, followed by a return movement away from it. The study was
      expanded to incorporate clinical aspects, whereby the composite resin was in
      direct contact with dental tissue, as in a restoration. Tests were performed with
      surface-treated cavity moulds, as in restoration placement, and without surface
      treatment. Results indicated that the shrinkage was highly dependent upon the
      region under investigation, as well as on the state of the surface.

PMID- 11521761
TI  - Improved mathematical model of the wear of the cup articular surface in hip joint
      prostheses and comparison with retrieved components.
AB  - This paper presents an analytical model of the cobalt-based alloy-ultra-high
      molecular weight polyethylene (UHMWPE) wear coupling. Based on a previous model
      in which the cup wear volume over a gait cycle (WG) was calculated under the
      simplifying assumption of an ideal rigid coupling, the current version proposes a
      more realistic wear simulation. All three components of the hip loading force
      were considered for the contact pressure calculation and all three components of
      the hip motion were taken into account for the sliding distance calculation. The
      contact pressure distribution was calculated on the basis of the Hertzian theory
      for the elastic contact of two bodies with non-conforming geometrical shapes. The
      wear factor was taken from hip simulator wear tests. The calculated WG is 67 x
      10(-6) mm3 for a standard reference patient. The parametric model simulations
      show that WG increases linearly with the patient weight, femoral head diameter
      and surface roughness. It increases non-linearly to a maximum and decreases to an
      asymptotic value with increasing cup/head clearance and with cup isotropic
      elastic modulus. The cup orientation in the pelvis affects only slightly the
      total amount of WG whereas it is the dominant factor affecting the shape of the
      wear distribution. The iso-wear maps show paracentral patterns at low cup
      inclination angles and marginal patterns at higher inclination angles. The
      maximum wear depth is supero-posterior when the cup is in neutral alignment and
      supero-anterior at increasing anteversion angles. Complex patterns with a
      combination of paracentral and marginal wear were obtained at specific clearance
      values and cup orientations. The results of the simulations are discussed in
      relation to the wear distribution measured on the articular surface of 12 UHMWPE
      components retrieved from failed hip joint prostheses, after a period of in situ
      functioning.

PMID- 11521762
TI  - Effect of blood flow, tumour and cold stress in a female breast: a novel time
      accurate computer simulation.
AB  - Breast cancer is a dreadful disease among women and early detection helps in
      achieving a cure. The mammogram is presently the standard tool for detecting
      breast abnormality, but its sensitivity is lower for women with dense breasts. It
      has been found that women with an abnormal thermogram are at a higher risk and
      have a poorer prognosis. However, performing and interpreting thermograms
      requires meticulous training. Computer simulations can be an additional tool to
      help the clinician in the interpretation. In this paper, a novel and flexible
      finite element model of a female breast is developed. Both steady state and time
      dependent solutions are obtained. Steady state solutions globally match
      experimental thermographic results with the proper choice of blood perfusion
      source terms, tissue thickness and geometric scaling factor. Although the
      simulations may not be useful in providing a unique solution (i.e. exact size and
      location of the tumour owing to the complex physiological relationship between
      the tumour and the breast surface temperature), it would nevertheless help in the
      'analysis by elimination'. An example of this type of analysis is also presented.

PMID- 11521763
TI  - A fracture movement monitoring system to aid in the assessment of fracture
      healing in humans.
AB  - This paper presents a new design for a device to monitor the motion of fracture
      fragments in diaphyseal tibial fractures. The device measures the motion that
      occurs at the fracture site when loaded by gait or by manipulation. It has
      undergone rigorous calibration and acceptance trials. The device has been used in
      ethically approved research clinics held at the North Staffordshire Hospital (40
      patients). The paper presents a selection of results obtained using the new
      device. The results demonstrate several new ways of assessing fracture healing by
      examining fracture site motion. The following conclusions were drawn: 1. If
      fracture monitoring devices are to be attached to bone screws, it is essential to
      minimize bone screw errors. To do this, each patient must have similar bone screw
      lengths, orientations, alignment and siting. This is only achievable using a
      peroperative reduction device. 2. If fracture stiffness is to be used as a
      measure of fracture healing, load rate should be controlled; at the very least
      strain rate should be controlled. 3. It is imperative that fracture stiffness be
      measured in more than one plane by a biplanar device so that asymmetry may be
      accommodated. 4. Fracture stiffness, on its own, is probably not a sufficiently
      rigorous measure of healing end-point. The quantifiably viscoelastic properties
      of healing callus should be taken into account.

PMID- 11521764
TI  - Three-dimensional metacarpophalangeal joint kinematics using two markers on the
      phalanx.
AB  - A protocol for analysing three-dimensional metacarpophalangeal (MCP) joint motion
      in vivo using two markers on the proximal phalanx is described. The analysis uses
      an assumption that the rotation of the phalanx about its own long axis is zero.
      In an experimental study 24 volunteers had surface markers applied to the dorsal
      surfaces of their hands and index and long finger proximal phalanges, with three
      dimensional marker positions recorded in two hand and finger postures in an
      incomplete box design using a test-retest protocol. Kinematic parameters from the
      optoelectronic system were compared with those obtained from three-dimensional
      reconstruction of bone landmarks and of the marker positions identified on
      stereoradiographs. Pronation/supination angles obtained from bone landmarks
      showed high test-retest variability, reflecting the difficulty in obtaining
      reliable pronation/supination data in small bones without the use of implanted
      markers. Changes in MCP joint extension and deviation angles determined using two
      surface markers agree with those obtained from bone landmarks. The results
      indicate a reproducible protocol for tracking MCP joint motion using only two
      phalangeal markers, suggesting that the 'no-rotation assumption' can be applied
      without affecting measures of extension and deviation motion in the normal joint.

PMID- 11521765
TI  - A novel instrumented ring for the measurement of grip force adjustments during
      precision grip tasks.
AB  - A wide range of scientific and clinical research studies use the measurement of
      grip force to quantify hand function and activities during daily living. Many
      applications of instrumented objects can be found in the biomechanical and
      neurophysiological literature. However, these were found not to be suitable for
      the measurement of grip force and force modulations during precision grip
      independently from the hand orientation. The low-cost precision grip force
      transducer described here is capable of recording magnitude, direction and
      modulation of the force exerted on a closed ring. The design is based on a
      standard proving ring, onto which a second set of strain gauges is applied. The
      outputs of both Wheatstone bridges yield a unique signature for every position
      under a two-point load. The tested aluminium ring had an outer diameter of 83 mm,
      a wall thickness of 3 mm and a height of 12 mm. With eight single bending strain
      gauges used, the maximum load was 100 N. During a grip task, tremor components
      from d.c. to 45 Hz could be detected. The newly developed ring might therefore
      find a use in many biomechanical and neurophysiological studies as a tool for
      measuring grip force and its fine modulations.

PMID- 11521766
TI  - Sources of age-related recognition difficulty for time-compressed speech.
AB  - Older people frequently show poorer recognition of rapid speech or time
      compressed speech than younger listeners. The present investigation sought to
      determine if the age-related problem in recognition of time-compressed speech
      could be attributed primarily to a decline in the speed of information processing
      or to a decline in processing brief acoustic cues. The role of the availability
      of linguistic cues on recognition performance was examined also. Younger and
      older listeners with normal hearing and with hearing loss participated in the
      experiments. Stimuli were sentences, linguistic phrases, and strings of random
      words that were unmodified in duration or were time compressed with uniform time
      compression or with selective time compression of consonants, vowels, or pauses.
      Age effects were observed for recognition of unmodified random words, but not for
      sentences and linguistic phrases. Analysis of difference scores (unmodified
      speech versus time-compressed speech) showed age effects for time-compressed
      sentences and phrases. The forms of time compression that were notably difficult
      for older listeners were uniform time compression and selective time compression
      of consonants. Indeed, poor performance in recognizing uniformly time-compressed
      speech was attributed primarily to difficulty in recognizing speech that
      incorporated selective time compression of consonants. Hearing loss effects were
      observed also for most of the listening conditions, although these effects were
      independent of the aging effects. In general, the findings support the notion
      that the problems of older listeners in recognizing time-compressed speech are
      associated with difficulty in processing the brief, limited acoustic cues for
      consonants that are inherent in rapid speech.

PMID- 11521767
TI  - Is there a relationship between speech and nonspeech auditory processing in
      children with dyslexia?
AB  - A group of 8 young teenagers with dyslexia were compared to age-matched control
      participants on a number of speech and nonspeech auditory tasks. There were no
      differences between the control participants and the teenagers with dyslexia in
      forward and simultaneous masking, nor were there any differences in frequency
      selectivity as indexed by performance with a bandstop noise. Thresholds for
      backward masking in a broadband noise were elevated for the teenagers with
      dyslexia as a group. If this deficit in backward masking had an influence on
      speech perception, we might expect the perception of "ba" versus "da" to be
      affected, as the crucial second formant transition is followed by a vowel. On the
      other hand, as forward masking is not different in the two groups, we would
      expect the perception of "ab" versus "ad" to be unaffected, as the contrastive
      second formant transition is preceded by a vowel. Overall speech identification
      and discrimination performance for these two contrasts was superior for the
      control group but did not differ otherwise. Thus, the clear group deficit in
      backward masking in the group with dyslexia has no simple relationship to the
      perception of crucial acoustic features in speech. Furthermore, the deficit for
      nonspeech analogues of the speech contrasts (second formants in isolation) was
      much less marked than for the speech sounds, with 75% of the listeners with
      dyslexia performing equivalently to control listeners. The auditory deficit
      cannot therefore be simply characterized as a difficulty in processing rapid
      auditory information. Either there is a linguistic/phonological component to the
      speech perception deficit, or there is an important effect of acoustic
      complexity.

PMID- 11521768
TI  - Human auditory brainstem response to temporal gaps in noise.
AB  - Gap detection is a commonly used measure of temporal resolution, although the
      mechanisms underlying gap detection are not well understood. To the extent that
      gap detection depends on processes within, or peripheral to, the auditory
      brainstem, one would predict that a measure of gap threshold based on the
      auditory brainstem response (ABR) would be similar to the psychophysical gap
      detection threshold. Three experiments were performed to examine the relationship
      between ABR gap threshold and gap detection. Thresholds for gaps in a broadband
      noise were measured in young adults with normal hearing, using both
      psychophysical techniques and electrophysiological techniques that use the ABR.
      The mean gap thresholds obtained with the two methods were very similar, although
      ABR gap thresholds tended to be lower than psychophysical gap thresholds. There
      was a modest correlation between psychophysical and ABR gap thresholds across
      participants. ABR and psychophysical thresholds for noise masked by temporally
      continuous, high-pass, or spectrally notched noise were measured in adults with
      normal hearing. Restricting the frequency range with masking led to poorer gap
      thresholds on both measures. High-pass maskers affected the ABR and
      psychophysical gap thresholds similarly. Notched-noise-masked ABR and
      psychophysical gap thresholds were very similar except that low-frequency,
      notched-noise-masked ABR gap threshold was much poorer at low levels. The ABR gap
      threshold was more sensitive to changes in signal-to-masker ratio than was the
      psychophysical gap detection threshold. ABR and psychophysical thresholds for
      gaps in broadband noise were measured in listeners with sensorineural hearing
      loss and in infants. On average, both ABR gap thresholds and psychophysical gap
      detection thresholds of listeners with hearing loss were worse than those of
      listeners with normal hearing, although individual differences were observed.
      Psychophysical gap detection thresholds of 3- and 6-month-old infants were an
      order of magnitude worse than those of adults with normal hearing, as previously
      reported; however, ABR gap thresholds of 3-month-old infants were no different
      from those of adults with normal hearing. These results suggest that ABR gap
      thresholds and psychophysical gap detection depend on at least some of the same
      mechanisms within the auditory system.

PMID- 11521769
TI  - Effects of abdominal trussing on breathing and speech in men with cervical spinal
      cord injury.
AB  - Abdominal trussing constitutes an inward fixation of the abdominal wall. In the
      context of speech habilitation/rehabilitation, it is sometimes used to supplant,
      in part, the function of a paralyzed or paretic abdominal wall. A paralyzed or
      paretic abdominal wall may be found in individuals with cervical spinal cord
      injury or in individuals with other neurologic disorders, such as muscular
      dystrophy. This research was designed to study the effects of trussing as a
      dinical treatment. A study was designed to systematically and precisely place the
      abdominal wall at one position (50% inward) to study the effects of trussing (as
      compared to an untrussed condition) on lung volume and oral reading in three men
      with cervical spinal cord injury (C5-C6). Results showed that abdominal trussing
      increased vital capacity, realized via an increase of inspiratory capacity,
      presumably by optimization of the function of the diaphragm. With the increase in
      inspiratory capacity, longer utterance duration for oral reading was observed.
      With increased utterance duration, more syllables were produced per utterance,
      and pauses occurred at appropriate linguistic locations. Oral reading samples for
      trussed and untrussed conditions were submitted to preference judgment by a group
      of 10 judges. For two of the three men studied, oral reading during trussing was
      preferred because of longer phrases and pauses taken at suitable linguistic
      boundaries. The findings from this study support clinical impressions that
      abdominal trussing may be useful in improving speech in individuals with a
      paralyzed or paretic abdomen whose breathing function for speech is diminished.

PMID- 11521770
TI  - Age-related changes in motor control during articulator visuomotor tracking.
AB  - The present study provides normative data on changes in visuomotor control of the
      oral-facial system across the lifespan. Control of the lower lip, jaw, and larynx
      (i.e., fundamental frequency) was examined using a nonspeech visuomotor tracking
      (VMT) task, where subjects move the articulator of interest to track a moving
      target on an oscilloscope screen. This task examines articulator motor control
      during movements that are similar to speech but that do not impose linguistic
      units or the demands of coordinating multiple structures. Accuracy and within-
      and between-subject variability in tracking performance were measured by cross
      correlation, gain ratio, phase shift, and target-tracker amplitude difference.
      Cross-correlation analyses indicated that performance of children (aged 8;2 to
      17;0 [years;months]) and older adults (aged 45;1 to 84;3) is poorer than that of
      younger adults (aged 17;1 to 45;0). Accuracy of movement amplitude tended to
      increase during development and decline with aging, whereas age did not appear to
      influence accuracy of temporal parameters in lip and jaw tracking. In contrast,
      age tended to influence individual variability in temporal but not amplitude
      parameters. Differences were noted between articulators. The data complement
      previous studies that considered accuracy and variability of articulator movement
      during speech. The VMT method and the data provided may be applied to assessment
      of impairments in the motor speech system and to differential diagnosis of motor
      speech versus linguistically based disorders.

PMID- 11521771
TI  - Phonological pattern frequency and speech production in adults and children.
AB  - Recent studies have suggested that both adults and children are sensitive to
      information about phonological pattern frequency; however, the influence of
      phonological pattern frequency on speech production has not been studied
      extensively. The current study examined the effect of phonological pattern
      frequency on the fluency and flexibility of speech production. Normal- and fast-
      rate nonsense-word repetitions of three groups of participants (preschool
      children, school-aged children, and adults) were analyzed. Subjective ratings of
      the wordlikeness of nonsense words, percentage phonemes correctly repeated, mean
      duration, and durational variability were measured. In the first experiment,
      ratings of the wordlikeness of nonsense words were found to correlate with the
      pattern frequency of sequences embedded in them. In the second analysis, it was
      found that children, but not adults, repeated infrequent sequences of phonemes
      less accurately than frequent sequences. In the third experiment, infrequent
      sequences were produced with longer durations than frequent ones, with children
      demonstrating a larger difference between frequent and infrequent sequences than
      adults. Phonological pattern frequency also influenced variability in duration:
      infrequent sequences of sounds were more variable than frequent ones. Thus, there
      appears to be an influence of phonological pattern frequency on speech, and, for
      some measures, a larger effect size is noted for children.

PMID- 11521772
TI  - Consistency of voice produced by patients with adductor spasmodic dysphonia: a
      preliminary investigation.
AB  - Adductor spasmodic dysphonia (ADSD) is an idiopathic focal laryngeal movement
      disorder causing involuntary and uncontrollable spasms in the vocal fold
      musculature, primarily during voice onset. Although phonatory instability has
      been reported through clinical observation and empirical study, no examination of
      phonatory performance consistency in ADSD has been done. Phonatory instability
      refers to phonatory unsteadiness and has been previously defined by the presence
      of acoustic aberrations during speech. Performance consistency pertains to
      variations in these phonatory aberrations across repeated trials or over time.
      This study focused on the phonatory performance consistency of those with ADSD by
      using three acoustic measures of phonatory instability. Twenty patients with ADSD
      were recorded during three trials of reading a standard passage. Eight of the 20
      patients were recorded twice during two separate recording sessions held
      approximately 6 months apart. The number of phonatory breaks, frequency shifts,
      and aperiodic segments were the dependent measures. Data were subjected to
      inferential statistical analysis to test for significant differences among the
      measures in two conditions: across three trials produced within one recording
      session and across multiple trials produced during two distinct recording
      sessions. No significant differences were found for any of the measures either as
      a function of trials recorded on the same day or across the two recording
      sessions. The data suggest a need for describing phonatory instability and
      performance consistency as separate entities with regard to neurological voice
      disorders.

PMID- 11521773
TI  - Emergence of a vowel system in a young cochlear implant recipient.
AB  - This report chronicles changes in vowel production by a congenitally deaf child
      who received a multichannel cochlear implant at 19 months. The emergence of
      Hannah's vowel system was monitored by transcribing vocalic segments from
      spontaneous utterances produced during two 30-minute recording sessions before
      implant surgery and 12 monthly recording sessions after her implant was
      activated. Vowel types were included in her inventory whenever transcribers
      independently agreed that a vocalization contained an allophone of a given vowel
      type. Hannah exhibited three vowel types before implantation. A total of nine
      different vowel types were observed during her first year of implant experience,
      and a full range of place and height categories was represented. Acoustic
      analyses revealed that Hannah's vowel space was near normal in size and that the
      formant structures of /i/ and /u/ were distinctive from other point vowels.
      Formant regions for /ae/ and /a/ showed some overlap. Taken together with a
      previous report of her vocal development (D. J. Ertmer & J. A. Mellon, 2001),
      Hannah appears to have made substantial progress in speech development during her
      first year of implant use.

PMID- 11521774
TI  - Neural systems for sentence processing in stuttering.
AB  - The role of neurolinguistic factors in stuttering was investigated by determining
      whether individuals who stutter display atypical neural functions for language
      processing, even with no speech production demands. Event-related brain
      potentials (ERPs) were obtained while 9 individuals who stutter (IWS) and 9
      normally fluent speakers (NS) read sentences silently. The ERPs were elicited by:
      (a) closed-class words that provide structural or grammatical information, (b)
      open-class words that convey referential meaning, and (c) semantic anomalies
      (violations in semantic expectation). In standardized tests, adult IWS displayed
      similar grammatical and lexical abilities in both comprehension and production
      tasks compared to their matched, normally fluent peers. Yet the ERPs elicited in
      IWS for linguistic processing tasks revealed differences in functional brain
      organization. The ERPs elicited in IWS were characterized by reduced negative
      amplitudes for closed-class words (N280), open-class words (N350), and semantic
      anomalies (N400) in a temporal window of approximately 200-450 ms after word
      onsets. The overall pattern of results indicates that alterations in processing
      for IWS are related to neural functions that are common to word classes and
      perhaps involve shared, underlying processes for lexical access.

PMID- 11521775
TI  - Effects of syllable affiliation and consonant voicing on temporal adjustment in a
      repetitive speech-production task.
AB  - This paper presents the results of an acoustic speech-production experiment in
      which speakers repeated simple syllabic forms varying in consonantal voicing in
      time to a metronome that controlled repetition rate. Speakers exhibited very
      different patterns of tempo control for syllables with onsets than for syllables
      with codas. Syllables with codas exhibited internal temporal consistency, leaving
      junctures between the repeated syllables to take up most of the tempo variation.
      Open syllables with onsets, by contrast, often exhibited nearly proportional
      scaling of all of the acoustic portions of the signal. Results also suggest that
      phonemic use of vowel duration as a cue to voicing acted to constrain temporal
      patterns with some speakers. These results are discussed with respect to possible
      models of local temporal adjustment within a context of global timing
      constraints.

PMID- 11521776
TI  - The modification of speech naturalness during rhythmic stimulation treatment of
      stuttering.
AB  - This study investigated the modification of speech naturalness during stuttering
      treatment. It systematically replicated an earlier study (Ingham & Onslow, 1985)
      that demonstrated that unnatural-sounding stutter-free speech could be shaped
      into more natural-sounding stutter-free speech by using regular feedback of
      speech-naturalness ratings during speaking tasks. In the present study, the some
      procedure was used with three persons who stutter-2 adolescent girls and 1 adult
      man-during rhythmic stimulation conditions. The two adolescent participants spoke
      only English, but Spanish was the first and English the second language (ESL) of
      the adult participant. For the 2 adolescents, it was demonstrated that their
      unnatural-sounding rhythmic speech could be shaped to levels found among normally
      fluent speakers without losing the fluency-inducing benefits of rhythmic speech.
      The findings indicate that speech-naturalness feedback may be a powerful
      procedure for overcoming a problematic aspect of rhythmic speech treatments of
      stuttering. However, it was not possible to deliver reliable speech-naturalness
      feedback to the adult ESL speaker, who also displayed a strong dialect. The study
      highlights the need to find strategies to improve interjudge agreement when using
      speech naturalness ratings with speakers who display a strong dialect.

PMID- 11521777
TI  - Influence of mothers' slower speech on their children's speech rate.
AB  - This study investigated the effects on children's speech rate when their mothers
      talked more slowly. Six mothers and their normally speaking 3-year-olds (3 girls
      and 3 boys) were studied using single-subject A-B-A-B designs. Conversational
      speech rates of mothers were reduced by approximately half in the experimental
      (B) conditions. Five of the six children appeared to reduce their speech rates
      when their mothers spoke more slowly. This was confirmed by paired t tests (p <
      .05) that showed significant decreases in the 5 children's speech rate over the
      two B conditions. These findings suggest that when mothers substantially decrease
      their speech rates in a controlled situation, their children also decrease their
      speech rates. Clinical implications are discussed.

PMID- 11521778
TI  - Recovery from early stuttering: additional issues within the Onslow & Packman
      Yairi & Ambrose (1999) exchange.

PMID- 11521779
TI  - Longitudinal studies of childhood stuttering: evaluation of critiques.

PMID- 11521780
TI  - Language development and symbolic play in children with and without familial risk
      for dyslexia.
AB  - The purposes of this study were to investigate (a) whether children in families
      with a positive history of dyslexia were more likely to show delays in language
      development than children without family risk and (b) whether a delayed onset of
      expressive language (late talking) predicted later language development. We
      analyzed the language development of 200 children longitudinally at 14, 24, 30,
      and 42 months and assessed their symbolic play at 14 months. Half of the children
      (N = 106) were from families with a history of dyslexia (the Dyslexia Risk [DR]
      group), and other children served as age-matched controls. Parental reports and
      structured tests were used to assess children's receptive and expressive language
      and symbolic play. No differences emerged between the two groups in receptive
      language, symbolic play, or on the Bayley MDI. The groups, however, diverged in
      expressive language measures. The maximum sentence length at 2 years and object
      naming and inflectional morphology skills at 3.5 years were higher for the
      control group than for the DR group. Reynell receptive score at 2.5 years
      provided the greatest unique contribution to the prediction of the children's
      receptive and expressive language. Children's risk status did not contribute to
      receptive language, but provided a significant contribution to their expressive
      language at 3.5 years, even after the variance associated with parental education
      and children's previous language skills was controlled. Late talkers in the DR
      group differed from the other members of the DR group in both receptive and
      expressive language at 3.5 years, although in the control group children with a
      late-talking history performed at age-level expectations. The findings suggest
      that children with a familial risk for dyslexia and with a history of late
      talking are at higher risk for delays in language acquisition than children
      without the familial risk for dyslexia.

PMID- 11521781
TI  - Syllable onsets II: three-element clusters in phonological treatment.
AB  - This study extends the application of the Sonority Sequencing Principle, as
      reported in J. A. Gierut (1999), to acquisition of word-initial 3-element
      clusters by children with functional phonological delays (ages in years;months:
      3;4 to 6;3). The representational structure of 3-element clusters is complex and
      unusual because it consists of an s-adjunct plus a branching onset, which
      respectively violate and conform to the Sonority Sequencing Principle. Given the
      representational asymmetry, it is unclear how children might learn these clusters
      in treatment or whether such treatment may even be effective. Results of a single
      subject staggered multiple-baseline experiment demonstrated that children learned
      the treated 3-element cluster in treatment but showed no further generalization
      to similar types of (asymmetric) onsets. Treatment of 3-element clusters did,
      however, result in widespread generalization to untreated singletons, including
      affricates. Moreover, there was differential generalization to untreated 2
      element clusters, with individual differences being traced to the composition of
      children's singleton inventories. Theoretically, the results suggest a segmental
      syllabic interface that holds predictive potential for determining the
      effectiveness and effects of clinical treatment as based on the notion of
      linguistic complexity.

PMID- 11521782
TI  - Grammatical morphology deficits in Spanish-speaking children with specific
      language impairment.
AB  - The focus of this study was the use of grammatical morphology by Spanish-speaking
      preschoolers with specific language impairment (SU). Relative to both same-age
      peers and younger typically developing children with similar mean lengths of
      utterance (MLUs), the children with SU showed more limited use of several
      different grammatical morphemes. These limitations were most marked for noun
      related morphemes such as adjective-agreement inflections and direct object
      clitics. Most errors on the part of children in all groups consisted of
      substitutions of a form that shared most but not all of the targets grammatical
      features (e.g., correct tense and number but incorrect person). Number errors
      usually involved singular forms used in plural contexts; person errors usually
      involved third person forms used in first person contexts. The pattern of
      limitations of the children with SU suggests that, for languages such as Spanish,
      additional factors might have to be considered in the search for clinical markers
      for this disorder. Implications for evaluation and treatment of language
      disorders in Spanish-speaking children are also discussed.

PMID- 11521783
TI  - Rapid auditory processing and phonological ability in normal readers and readers
      with dyslexia.
AB  - According to a prominent theory, the phonological difficulties in dyslexia are
      caused by an underlying general impairment in the ability to process sequences of
      rapidly presented, brief sounds. Two studies examined this theory by exploring
      the relationships between rapid auditory processing and phonological processing
      in a sample of 82 normally reading children (Study 1) and by comparing 17
      children with dyslexia to chronological-age and reading-age control participants
      on these tasks (Study 2). In the normal readers, moderate correlations were found
      between the measure of rapid auditory processing (Auditory Repetition Task, or
      ART) and phonological ability. On the ART, the dyslexia group performed at a
      level similar to that of the reading-age control group but obtained scores that
      were significantly below those of the chronological-age control group. This
      difference was due to a subgroup of 4 children in the dyslexia group who had
      particular difficulty with the ART. The phonological skills of these individuals
      were not worse than those of the children in the dyslexia group who were
      unimpaired on the ART. The discussion argues that there is no evidence that
      phonoogical difficulties are secondary to impairments of rapid auditory
      processing, as measured by the ART, and highlights the need to examine the
      strategic and cognitive demands involved in tasks of rapid auditory processing.

PMID- 11521784
TI  - Primary non-Hodgkin's lymphomas of the liver with nodular and diffuse
      infiltration patterns have different prognoses.
AB  - BACKGROUND: Primary liver non-Hodgkin's lymphomas have peculiar clinical and
      biological patterns. This study correlates these patterns with pathology and
      outcome. PATIENTS AND METHODS: Clinical records and histology of patients with
      primary liver non-Hodgkin's lymphoma, treated at our institution over a 20-year
      period, were reviewed. Lymphoproliferations occurring after liver transplantation
      were excluded. Survival analyses were performed with patients from the other
      published series (62 patients). RESULTS: Our series included eight patients.
      Three patients had a nodular liver infiltration, corresponding to a large B-cell
      lymphoma. Five patients had a diffuse liver infiltration, of whom three had a T
      cell lymphoma with predominant sinusoid infiltration, and two had a large B-cell
      lymphoma. Patients with diffuse liver infiltration presented with hepatomegaly,
      and two of these also had acute liver failure. Diffuse infiltration had a worse
      prognosis than nodular infiltration (P = 0.0033). Among these latter patients,
      those treated with an anthracycline-based chemotherapy had a better outcome (P <
      0.0001). CONCLUSIONS: Patients with primary liver lymphomas can be classified in
      two groups, depending on the type of infiltration. Those with nodular
      infiltration may benefit from anthracycline-based chemotherapy. Diffuse
      infiltration has a bad prognosis, and should be suspected in patients presenting
      with altered liver functions and hepatomegaly.

PMID- 11521785
TI  - A randomized trial of four cycles of adjuvant AC (adriamycin + cyclophosphamide)
      +/- two cycles of EP (etoposide + cisplatin) in node positive patients with
      breast cancer.
AB  - BACKGROUND: Four cycles of AC have been accepted as the standard chemotherapy in
      breast cancer. In the present randomized study we aimed to assess the efficacy of
      adjuvant etoposide + cisplatin (EP) combination following four cycles of standard
      adriamycin + cyclophosphamide (AC) in premenopausal patients with operable breast
      cancer and axillary lymph node metastasis. PATIENTS AND METHODS: Premenopausal
      patients with positive axillary lymph nodes following curative modified radical
      mastectomy were randomized to either four cycles of AC (82 patients) or four
      cycles of AC + two cycles of EP (83 patients). RESULTS: Median follow-up is 72
      months. All randomized and eligible patients are included in the analysis (AC: 80
      patients, AC + EP: 78 patients). The five-year disease-free survival (DFS) for
      the AC + EP group was significantly better when compared to AC group (45.5% vs.
      30.4%; P = 0.048). Again, the five-year overall survival (OS) of the whole group
      was in favor of AC + EP arm, though without statistical significance (68.6% vs.
      59.1%; P = 0.247). CONCLUSION: Two cycles of EP following four cycles of AC
      decreased the relapse rate in operable breast cancer patients.

PMID- 11521786
TI  - Combined modality treatment for locally advanced squamous-cell carcinoma of the
      oropharynx in a woman with Bloom's syndrome: a case report and review of the
      literature.
AB  - We describe a case of locally advanced unresectable squamous-cell carcinoma of
      the oropharynx in a young woman with Bloom's syndrome. She was treated with
      radical radiation therapy and concurrent chemotherapy (cisplatin and 5
      flurouracil). She was unable to complete treatment due to the development of
      severe side effects: confluent mucositis, moist desquamating skin reaction,
      severe diarrhea and severe myelosupression with neutropenic sepsis. The limited
      relevant literature is presented. We conclude that chemotherapy should be used
      with extreme caution in Bloom's syndrome patients.

PMID- 11521787
TI  - Carcinocythemia as the single extension of breast cancer: report of a case and
      review of the literature.
AB  - Carcinocythemia (carcinoma cell leukemia) has been previously described as a
      rare, late and dramatic event occurring in widespread tumoral disease. We report
      a case of carcinocythemia occurring in a patient with a particularly indolent
      breast cancer. When a large amount of circulating tumor cells (CTC) appeared in
      the blood smears, neither visceral macrometastases nor massive bone marrow
      infiltration could be detected. We isolated CTC to perform cell cycle analysis
      and to study the expression of adhesion molecules. A fraction of the CTC was
      proliferating in the bloodstream but we detected no relevant anomaly of adhesion
      properties in the CTC. A post-mortem biopsy disclosed an exclusive sinusoidal
      infiltration of the liver. We propose that in this case, carcinocythemia resulted
      from the release of CTC from the visceral microcirculation where the
      proliferation occurred.

PMID- 11521788
TI  - Intra-arterial hepatic chemotherapy (IAHC) for liver metastases from colorectal
      cancer: need of guidelines for catheter positioning, port management, and anti
      coagulant therapy.

PMID- 11521789
TI  - Paclitaxel plus organoplatins: still the gold standard in advanced ovarian
      cancer?

PMID- 11521790
TI  - Chemotherapy in cervical cancer: is cisplatin alone still the standard of care?

PMID- 11521791
TI  - The revitalization of thalidomide.

PMID- 11521792
TI  - Surgical management of hepatic metastases from colorectal malignancies.
AB  - Liver metastasis represents the major cause of death of patients who have been
      treated for colorectal adenocarcinoma. Spontaneous survival rarely exceeds two
      years. Surgery can offer long-term survival and resection should be considered
      when liver metastases can be totally resected with clear margins and when there
      is no non-resectable extra-hepatic disease. The choice between anatomical or
      wedge resection depends on the number and the location of the metastases but does
      not influence survival. Clamping methods limit blood loss. Operative mortality is
      generally less than 5%. The five-year survival rate after surgical resection
      varies from 20% to 45% according to several prognostic factors. The longer
      survival is observed in patients with fewer than four lesions, with lesions
      smaller than 4 cm, without extra-hepatic disease, with lesions that appeared more
      than two years after the resection of a stage I or II colorectal cancer and whose
      CEA level is normal. After resection, follow-up can detect hepatic recurrence
      that can be treated with repeat hepatectomy. The efficacy of systemic
      chemotherapy using new agents can increase the number of patients amenable to
      surgery. Regional therapies with cryotherapy or radiofrequency ablation can help
      to treat unresectable or non-totally resectable lesions and may improve survival.
      The effects on survival of adjuvant treatments, including pre- or postoperative
      systemic or postoperative intra-arterial chemotherapy, are currently under
      evaluation.

PMID- 11521793
TI  - Cancer genetics in oncology practice.
AB  - Cancer is a genetic disease caused by the progressive accumulation of mutations
      in critical genes that control cell growth and differentiation. Completion of the
      Human Genome Project promises to revolutionize the practice of Medicine,
      especially Oncology care. The tremendous gains in the knowledge of the structure
      and function of human genes will surely impact the diagnosis, prognosis and
      treatment of cancer. Moreover, it will lead to more effective cancer control
      through the use of genetics to quantify individual cancer risks. This article
      reviews the current status of genetic testing and counseling for cancer risk
      assessment and will suggest a framework for integrating such counseling into
      oncology practice.

PMID- 11521794
TI  - Phase I dose-finding and pharmacokinetic study of docetaxel and vinorelbine as
      first-line chemotherapy for metastatic breast cancer.
AB  - BACKGROUND AND PURPOSE: Anthracycline-containing regimens are widely used in
      advanced breast cancer. However, there is a need for new, non-anthracycline
      regimens that are active in patients for whom anthracyclines are contraindicated.
      The aim of this study was to determine the maximum tolerated dose (MTD), the dose
      limiting toxicities (DLTs) and recommended doses of docetaxel and vinorelbine as
      first-line chemotherapy in patients with metastatic breast cancer. The
      pharmacokinetics of both drugs was also evaluated. PATIENTS AND METHODS: Thirty
      four women with first-line metastatic breast cancer were treated with docetaxel,
      60-100 mg/m2 (day 1), and vinorelbine, 20-22.5 mg/m2 (days 1 and 5), repeated
      every three weeks and administered on an outpatient basis. RESULTS: Two MTDs were
      determined: MTD1 was defined at the dose level using docetaxel 75 mg/m2, and
      vinorelbine 22.5 mg/m2 DLT being a grade 3 stomatitis that was more related to
      the dose of vinorelbine than that of docetaxel. Therefore, the study continued
      with a fixed dose of vinorelbine, 20 mg/m2, and docetaxel 85-100 mg/m2. MTD2 was
      defined at the dose level combining docetaxel, 100 mg/m2, and vinorelbine, 20
      mg/m2; DLTs were grade 3 stomatitis and severe asthenia. Fluid retention was
      observed in 41% of patients but was never severe or a reason for patient
      discontinuation. In comparison with historical experience, Daflon 500 did not
      seem to increase the efficacy of the three-day corticosteroid premedication by
      further reducing the incidence or severity of fluid retention. No significant
      neurotoxicity was observed and no patient discontinued the study due to this site
      effect. Activity was observed at all dose levels and at all metastatic sites,
      with an overall response rate of 71% (95% CI: 52.0%-85.8%). The median time to
      progression was 31.4 weeks (95% CI: 12-48 weeks) and median survival was 15.6
      months (95% CI: 2.6-26.6 months). The pharmacokinetics of docetaxel and
      vinorelbine were not modified between day 1 and day 3 when the two drugs were
      combined with the day 1 administration schedule used in this study. CONCLUSION:
      The recommended doses for phase II studies are docetaxel, 75 mg/m2 (day 1), plus
      vinorelbine, 20 mg/m2 (days 1 and 5), repeated every three weeks. At these doses,
      the combination was found to be active and well tolerated.

PMID- 11521795
TI  - A National Cancer Institute of Canada clinical trials group phase II study of
      eniluracil (776C85) and oral 5-fluorouracil in patients with advanced squamous
      cell head and neck cancer.
AB  - BACKGROUND/PATIENTS AND METHODS: Thirty-two patients with recurrent head and neck
      cancer (HNC) following radiotherapy and/or surgery were treated with eniluracil
      (10 mg/m2) and 5-fluorouracil (5-FU) (1 mg/m2) (E5F) orally twice daily for 28
      days followed by a seven-day treatment free period. Thirty-five-day cycles were
      repeated until disease progression, unacceptable toxicity or patient refusal.
      Doses were modified for toxicity. Standard toxicity and response criteria were
      used. RESULTS: Thirty-two patients were accrued; thirty-two and twenty-eight
      patients were evaluable for toxicity and response, respectively. Twelve patients
      received three or more cycles of E5F. Drug related toxicities were usually grade
      1-2 intensity and included lethargy, nausea or diarrhea (> or = 25% of patients),
      and anorexia, rash or itch, stomatitis or vomiting (12%-24% of patients).
      Hematologic toxicity was generally mild; two patients experienced grade 3-5
      leukopenia or thrombocytopenia. No significant biochemical toxicity was seen. One
      patient was withdrawn (severe nausea and vomiting) and one patient died because
      of drug related toxicity (thrombocytopenia). In the final analysis there were one
      complete and four partial responses for a 15.6% overall response. CONCLUSIONS:
      E5F demonstrates activity in chemotherapy naive patients with advanced HNC cancer
      with acceptable toxicity profile. Further investigation of E5F with other active
      agents is warranted in HNC.

PMID- 11521796
TI  - Paclitaxel plus topotecan treatment for patients with relapsed or refractory
      aggressive non-Hodgkin's lymphoma.
AB  - BACKGROUND: Used as single agents, paclitaxel and topotecan have demonstrated
      promising activity in treating patients with relapsed aggressive non-Hodgkin's
      lymphoma (NHL). We conducted a phase II clinical trial to investigate the
      activity and tolerability of the combination of both drugs. PATIENTS AND METHODS:
      Patients with refractory or relapsed aggressive NHL who had previously been
      treated with a maximum of two prior chemotherapeutic regimens were given
      intravenous infusions of paclitaxel 200 mg/m2 over three hours on day one and
      topotecan 1 mg/m2 over 30 minutes daily from days one to five. All patients
      received daily subcutaneous injections of filgrastim (granulocyte colony
      stimulating factor) 5 microg/kg starting 24 hours after the last dose of
      chemotherapy until neutrophil recovery. Treatments were repeated every three
      weeks for a maximum of six courses. Patients who achieved partial remission or
      complete remission (CR) after at least two courses were offered stem cell
      transplantation, if eligible. RESULTS: Of the 71 patients eligible for this
      trial, 66 (93%) were evaluable for treatment response. The median age was 53
      years (range 23 to 74 years). Thirty-six percent of the patients had previously
      been treated with ara-C/platinum-based regimens, and 48% failed to achieve CR
      after primary induction therapy. Sixty-seven percent of the patients had elevated
      lactate dehydrogenase levels at the time of treatment initiation. The overall
      response rate was 48% (95% confidence interval (95% CI): 36%-61%). Patients who
      had primary refractory disease had a response rate of 31%, compared with 65% for
      patients who did not. Similarly, the response rate of patients who failed to
      achieve CR after their most recent previous therapy was 37%, compared with a 65%
      response rate in patients who relapsed from a first or second CR. The median
      duration of response was six months. A total of 199 courses were given, with a
      median of three courses per patient. Neutropenia at levels < or = 500 leukocytes
      per microliter was observed after 32% of the courses, and thrombocytopenia at
      levels < or = 20,000 platelets per microliter was observed after 17% of the
      courses. Grade 3-4 neutropenic fever occurred after 6% of the courses. Non
      hematologic toxic effects were predominantly grade 1-2. CONCLUSION: The
      combination of paclitaxel and topotecan is an effective first or second line
      salvage therapy for patients with relapsed or refractory aggressive NHL who had
      prior anthracycline- or platinum-based chemotherapy.

PMID- 11521797
TI  - A phase I-II study of synchronous chemoradiotherapy for poor prognosis locally
      advanced bladder cancer.
AB  - BACKGROUND: The management of locally advanced bladder cancer remains
      controversial with poor local control with radiotherapy alone. Synchronous
      chemotherapy regimens have yielded encouraging results in other primary sites.
      PATIENTS AND METHODS: Patients with T2-T4a N0/NX M0 bladder cancer were entered
      into this single centre phase I-II study. Patients received radiotherapy to 55 Gy
      in 20 fractions over four weeks. Concurrent chemotherapy was given with Mitomycin
      C 12 mg/m2 day 1 and 5-fluorouracil 500 mg/m2/24 hours weeks one and four of
      radiotherapy for five or seven days on each occasion. RESULTS: Thirty-one
      patients entered the trial from March 1998 to December 1999 (22: 5-day; 9: 7-day
      schedule). Median age was 68 (range 58-79) years, 23 males and 8 females. T2: 9
      (29%); T3a: 4 (12%); T3b: 9 (29%); T4: 9 (29%); TCC grade 2: 8 (26%) and grade 3:
      23 (74%); 14 of 31 had hydronephrosis. Ten of thirty-one had a GFR < 50 ml/min.
      Toxicity was mild to moderate with the five-day schedule. More severe toxicity
      was seen with the seven-day schedule: five of nine patients failed to complete
      planned therapy. Pathological complete response rate at three months was 74% (5
      day regimen) and 50% (7-day regimen). Overall 12-month survival was 65%.
      CONCLUSION: Chemoradiotherapy with the five-day schedule is feasible with
      acceptable toxicity in poor prognosis patients. A randomised trial is being
      launched.

PMID- 11521798
TI  - Impaired response of gastric MALT-lymphoma to Helicobacter pylori eradication in
      patients with autoimmune disease.
AB  - BACKGROUND AND AIMS: Gastric MALT-lymphoma is thought to be related to chronic
      antigenic stimulation provided by Helicobacter pylori (HP). As clonal expansion
      of gastric B cells not related to HP has been demonstrated in patients with
      autoimmune disease (AD), we have analysed whether AD adversely influences
      response of MALT-lymphoma following HP-eradication. PATIENTS AND METHODS:
      Retrospective analysis of all patients with early stage gastric MALT-lymphoma
      treated with HP-eradication was performed. The presence of AD was evaluated by
      personal questioning for specific symptoms and serologically by analysis of
      rheumatoid factor, antinuclear antibodies and thyroid autoantibodies. RESULTS: A
      total of 22 patients were identified receiving only antibiotic treatment for
      initial management, and six presented with an autoimmune condition: three had
      Sjogren's syndrome, one polymyalgia rheumatica, one autoimmune thyroiditis along
      with psoriasis, and one patient had only autoimmune thyroiditis. Successful
      eradication of HP was achieved in all patients, and 15 of 22 patients (68%)
      achieved complete response of the lymphoma, while none out of the six patients
      with an autoimmune disorder responded to HP-eradication. CONCLUSION: Apart from
      questioning the role of HP in the development of lymphoma in such patients, these
      results suggest that patients with autoimmune disease might not be optimal
      candidates for HP-eradication even in case of early stage lymphoma.

PMID- 11521799
TI  - The clinical value of [90Y-DOTA]-D-Phe1-Tyr3-octreotide (90Y-DOTATOC) in the
      treatment of neuroendocrine tumours: a clinical phase II study.
AB  - PURPOSE: The aim of this phase II study was to evaluate the tumour response of
      neuroendocrine tumours to targeted irradiation with the radiolabelled
      somatostatin analogue 90Y-DOTATOC. In addition, the palliative effect of 90Y
      DOTATOC treatment on the malignant carcinoid syndrome and tumour-associated pain
      was investigated. PATIENTS AND METHODS: Forty-one patients (mean age 53 years)
      with neuroendocrine gastroenteropancreatic and bronchial tumours were included.
      Eighty-two percent of the patients had therapy resistant and progressive disease.
      The treatment consisted of four intravenous injections of a total of 6000 MBq/m2
      90Y-DOTATOC, administered at intervals of six weeks. RESULTS: The overall
      response rate was 24%. For endocrine pancreatic tumours it was 36%. Complete
      remissions (CR) were found in 2% (1 of 41), partial remissions (PR) in 22% (9 of
      41), minor response in 12% (5 of 41), stable disease (SD) in 49% (20 of 41) and
      progressive disease (PD) in 15% (6 of 41). The median follow up was 15 months
      (range 1 month to 36 months). The median duration of response has not been
      reached at 26 months. The two-year survival time was 76 +/- 16%. Eighty-three
      percent of the patients suffering from the malignant carcinoid syndrome achieved
      a significant reduction of symptoms. The treatment was well tolerated. A
      reduction of pain score was observed in all patients (5 of 41) with morphine
      dependent tumour-associated pain. Side effects included grade III (NCIGC)
      pancytopenia in 5%, and vomiting shortly after injection in 23%. No grade III-IV
      renal toxicity was observed. CONCLUSION: Targeted radiotherapy with 90Y-DOTATOC
      is a novel, well-tolerated treatment for neuroendocrine tumours with a remarkable
      objective response rate, survival time, and symptomatic response.

PMID- 11521800
TI  - Carboplatin and gemcitabine in metastatic transitional cell carcinoma of the
      urothelium: effective treatment of patients with poor prognostic features.
AB  - PURPOSE: To evaluate the activity and toxicity of gemcitabine and carboplatin in
      consecutive patients presenting with locally advanced or metastatic transitional
      cell carcinoma of the urothelium (TCC). PATIENTS AND METHODS: Seventeen
      consecutive patients referred to a single institution with locally advanced or
      metastatic TCC were treated with carboplatin AUC 5 on day 1 and gemcitabine 1000
      mg/m2 on day 1 and 8 of a 21-day cycle. All patients were assessable for response
      and toxicity. Minimal eligibility criteria were used to minimize patient
      selection. RESULTS: Seventeen patients with measurable stage IV TCC of the
      urothelium were treated. The median age was 69 years (range 54-78), the median
      creatinine clearance was 56 ml/min (range 34-90) and 30% of patients had an ECOG
      performance score of two. Nine patients (53%) had visceral metastases and the
      majority of patients had multiple sites of metastases. There were three complete
      responses, seven partial responses, for an overall response rate of 58.8%.
      Responses were seen at all sites including the liver. One patient had a response
      within a previously irradiated field and three patients with prior chemotherapy
      had responses. Median overall survival was 10.5 months and median time to
      progression was 4.6 months. Toxicity was primarily haematologic with six patients
      having grade 3 neutropenia and six patients with grade 4 neutropenia. There were
      five cases of grade 3 and three cases of grade 4 thrombocytopenia. There were no
      episodes of febrile neutropenia and only one patient required admission for
      management of toxicity. Thirteen patients required dose reduction or delay due to
      neutropenia or thrombocytopenia. There were no treatment-related deaths.
      CONCLUSION: The combination of carboplatin and gemcitabine is active in
      metastatic transitional cell carcinoma of the urothelium with manageable toxicity
      in a relatively elderly group of patients with some poor prognostic features.

PMID- 11521801
TI  - Prevention of mucositis in bone marrow transplantation: a double blind randomised
      controlled trial of sucralfate.
AB  - Mucositis is still a leading side effect of high dose chemotherapy and
      irradiation delivered in autologous and allogeneic bone marrow transplantation.
      In this double blind randomised study, we tested the efficacy of sucralfate for
      the prevention of mucositis induced by such conditioning treatments. Treatment
      was started one day before conditioning regimen and patients were prospectively
      evaluated. The main endpoint was severe mucositis that was more frequent in the
      placebo group than in the sucralfate group (47% vs. 29%, P = 0.07). This trend
      was confirmed after adjustment on total body irradiation (TBI) (P = 0.06), the
      sole stratification parameter. Interestingly, patients receiving sucralfate
      showed a significant reduction of diarrhoea (25%) vs. 53%, P = 0.005). Overall,
      the preventive administration of sucralfate appears to be an effective procedure
      to diminish the occurrence of severe oral and intestinal mucositis in patients
      treated by high dose chemotherapy alone or combined with TBI before bone marrow
      transplantation.

PMID- 11521802
TI  - Etoposide phosphate with carboplatin in the treatment of elderly patients with
      small-cell lung cancer: a phase II study.
AB  - BACKGROUND: Although the average age of lung cancer patients is increasing, many
      elderly patients remain undertreated, mainly because of the fear of higher
      treatment toxicity in this category of patients. We conducted a study to evaluate
      the efficacy and tolerability of a combination therapy with carboplatin (C) and
      etoposide phosphate (EP) in elderly patients with Small-Cell Lung Cancer (SCLC).
      PATIENTS AND METHODS: Previously untreated patients older than 70 years with
      stage IIIB/IV SCLC received a combination of EP (100 mg/m2 D1, D2, D3) and C (D1,
      dose calculated according to the Calvert formula). Response rate, survival and
      toxicity were assessed. RESULTS: Thirty-eight patients (mean age 76 years, range
      70-88 years) received a total of 162 cycles. Eighteen patients (47%) received the
      six scheduled cycles. Thirty patients were evaluable for efficacy (2 CR and 20
      PR). The median survival was 237 days and the one-year probability of survival
      was 26%. The most common adverse effect was transient grade 3 or 4 neutropenia,
      observed during 57% of evaluable cycles, while five episodes of febrile
      neutropenia also occurred, with one fatal (bacteremia). It is noteworthy that no
      renal or liver toxicity was observed, and no mucitis was noted. Unfortunately, a
      relatively high proportion of patients died shortly after the start of the study.
      Although most deaths seemed unrelated to the treatment, the possibility of its
      exacerbatory effect on comorbidities, especially cardiovascular, cannot be
      excluded. CONCLUSION: The two-drug regimen of carboplatin and etoposide phosphate
      is feasible in most elderly patients with an acceptable toxicity, and the overall
      results suggest that patients even older than 70 years may benefit from full
      treatment. Therefore, consideration should be given to offering active treatment
      to most patients with SCLC, regardless of age but with special attention paid to
      comorbidities.

PMID- 11521803
TI  - Anthracycline-induced acute cardiotoxicity in adults treated for leukaemia.
      Analysis of the clinico-pathological aspects of documented acute anthracycline
      induced cardiotoxicity in patients treated for acute leukaemia at the University
      Hospital of Zurich, Switzerland, between 1990 and 1996.
AB  - BACKGROUND: Acute cardiotoxicity due to anthracyclines is a rare, but life
      threatening event. Interindividual sensitivity to anthracyclines is highly
      variable and cannot be predicted for the individual patient. PATIENTS AND
      METHODS: This is a retrospective study. Medical charts and autopsy reports of
      patients treated for acute leukemia between 1990 and 1996 at the University
      Hospital of Zurich, Switzerland were reviewed and searched for anthracycline
      associated acute cardiotoxicity. Patients with pre-existing heart disease known
      to be associated with cardiotoxicity were excluded. RESULTS: Seven patients
      treated for leukemia with proven anthracycline-associated acute cardiotoxicity
      were included. In six patients the direct cause of death was acute cardiotoxicity
      due to the treatment. One patient recovered from cardiac failure but died a few
      months later from refractory leukemia. Clinical symptoms were those of a heart
      failure. Pathological findings were dilatative cardiac hypertrophy and
      pericardial effusion. Microscopically the typical findings of myocardial fibrosis
      and perinuclear vacuolisated myocytes were seen. CONCLUSIONS: The awareness of
      acute adverse effects on cardiac performance by anthracyclines faciliates early
      recognition and prevention of heart failure. Reliable tests are needed for the
      early diagnosis of subclinical myocardial damage in order to identify patients at
      risk.

PMID- 11521804
TI  - Randomized phase III trial of bleomycin, vindesine, mitomycin-C, and cisplatin
      (BEMP) versus cisplatin (P) in disseminated squamous-cell carcinoma of the
      uterine cervix: an EORTC Gynecological Cancer Cooperative Group study.
AB  - PURPOSE: Three previous mitomycin-cisplatin-based chemotherapy trials conducted
      within the EORTC Gynecological Cancer Cooperative Group (GCCG) in patients with
      disseminated squamous-cell carcinoma of the uterine cervix (SCCUC) suggested that
      with such regimens a higher overall response rate and a higher complete response
      rate could be obtained compared to what might have been expected from cisplatin
      alone. In that respect the combination of bleomycin, vindesine (Eldesine),
      mitomycin C and cisplatin (BEMP) was the most promising. In the present study
      BEMP has been compared with the best single agent, cisplatin (P) in the
      expectation that improved response rates might translate into a better survival.
      PATIENTS AND METHODS: Eligible patients were those with SCCUC and disseminated
      measurable disease outside previously irradiated areas, aged < or = 75 years,
      with a WHO performance status < or = 2 and adequate bone marrow, renal, hepatic
      and pulmonary function, who gave consent according to regulations followed in
      individual institutions. Patients were randomized to BEMP: E 3 mg/m2 day 1, P 50
      mg/m2 day 1, B 15 mg (24-hour infusion) day 2-4 and M 8 mg/m2 (at alternate
      cycles), or P 50 mg/m2. The first four cycles were given every 3 weeks (induction
      phase). Subsequent cycles were given every four weeks (maintenance phase), during
      which B was deleted from BEMP (MEP). Patients failing on P could be treated with
      BEM. Of the 287 patients entered, 235 were eligible and 201 evaluable for
      response. RESULTS: BEMP induced a significantly higher response rate than P (42%
      vs. 25%, P = 0.006). There was no difference in complete response rate (11% vs.
      7%). BEMP was significantly more toxic than P (+/- BEM), both with respect to
      hematologic and nonhematologic toxicities. After a median follow-up of 6.1 years,
      survival curves were not significantly different. Median progression-free
      survival and overall survival were 5.3 and 10.1 months with BEMP and 4.5 and 9.3
      months with P (+/- BEM), respectively. In a multivariate analysis of prognostic
      factors for survival, a lower age (P = 0.003), a lower performance status (P =
      0.0001) and a short (<1 year) interval since diagnosis (P = 0.0152) were all
      associated with an increased risk of dying. For progression-free survival, lower
      age, prior radiotherapy, locoregional involvement and no prior surgery were
      associated with a high risk. Treatment with BEMP or P had no significant impact
      on survival, but for progression-free survival there was a trend in favor of BEMP
      (P = 0.0893). Adjusting for prognostic factors did not change the effect of
      treatment. CONCLUSIONS: Combination chemotherapy with BEMP produces more toxicity
      and more responses compared with cisplatin alone in patients with disseminated
      SCCUC, but this does not translate into a better survival. Therefore, in the
      palliative setting single-agent cisplatin should remain the standard therapy for
      these patients.

PMID- 11521805
TI  - Leanness and squamous cell oesophageal cancer.
AB  - BACKGROUND: Squamous cell oesophageal cancer is one of the few neoplasms
      inversely related to body mass index (BMI). However, it is not clear whether this
      is due to cancer-related weight loss or to other correlates of leanness. PATIENTS
      AND METHODS: 395 incident, histologically confirmed cases of squamous cell
      oesophageal cancer and 1,066 controls, admitted for acute, non-neoplastic
      diseases, in Italy and Switzerland. Odds ratios (ORs) were derived from multiple
      logistic regression, including terms for education, tobacco. alcohol, non-alcohol
      energy, fruit and vegetable intake. RESULTS: The ORs for the lowest vs. the
      highest quartile of BMI in the year before diagnosis were 2.0 in men, 1.6 in
      women, and 1.9 (95% confidence interval: 1.3-2.9) in both sexes combined. The
      association with leanness was stronger in heavy smokers, but was not accounted
      for by smoking and drinking, nor by differences in diet. Weight change in the
      decade prior to diagnosis showed no linear association with risk. However, cases
      were not leaner than controls at age 30 (OR = 0.6 for the lowest BMI quartile)
      and 50 (OR = 1.1). CONCLUSIONS: Leanness appears to be an indicator of squamous
      cell oesophageal carcinogenesis. However, low BMI in the distant past was
      unrelated to oesophageal cancer risk.

PMID- 11521806
TI  - Overexpression of the p73 gene is a novel finding in high-risk B-cell chronic
      lymphocytic leukemia.
AB  - The p73 protein shares structural and functional similarities with the tumour
      suppressor p53, but its role in neoplastic transformation is unknown. Alternative
      splicing leads to the expression of at least nine p73 C-terminal mRNA splice
      variants (alpha, beta, gamma, delta, epsilon, zeta, eta, eta1, theta). In this
      survey, we analyse the expression of p73 by real-time quantitative RT-PCR, its
      known C-terminal variants with an RT-PCR-Southern technique and by Western blot
      in samples of 51 patients with B-CLL, normal B lymphocytes from eight
      individuals, and five haematopoetic cell lines. p73alpha protein expression
      positively correlated with higher risk B-CLL stages (P = 0.046). Total p73 mRNA
      expression was higher (P = 0.01) and p73alpha protein more frequently detected (P
      = 0.008) in B-CLL compared with normal CD19+-B-lymphocytes. p73 C-terminal mRNA
      variants were expressed both in B-CLL and in normal B-lymphocytes, but their
      expression was biased since the gamma (P = 0.041), the theta (P < 0.001), and the
      eta variant (P = 0.033) prevailed in normal B-lymphocytes. In summary, we
      conclude that the accumulation of p73, the expression pattern of particular p73
      variants and its link to progression may play a distinct role in the molecular
      pathology B-CLL.

PMID- 11521807
TI  - Thalidomide in multiple myeloma, myelodysplastic syndromes and histiocytosis.
      Analysis of clinical results and of surrogate angiogenesis markers.
AB  - BACKGROUND: Thalidomide, as a single agent, has been recently found to induce a
      clinical response in one third of refractory or relapsed myeloma patients.
      Although it has been reported that thalidomide significantly inhibits
      angiogenesis. it is still unclear whether its clinical effect is mediated, at
      least in part, by its anti-angiogenic properties. PATIENTS AND METHODS: We
      evaluated thalidomide as a single agent in myeloma, myelodysplastic syndromes
      (MDS) and histiocytosis, i.e. hematological diseases characterized by increased
      angiogenesis, and measured prospectively a number of surrogate angiogenesis
      markers. RESULTS: Clinical responses were observed in 7 of 17 myeloma and 2 of 5
      MDS patients. The histiocytosis patient had a partial response. At the time of
      the best clinical response, plasma levels of angiogenic growth factors, vascular
      endothelial growth factor (VEGF) and basic-fibroblast growth factor (b-FGF), were
      significantly decreased, and flow cytometry indicated a decrease of activated
      endothelial cells in the bone marrow of responding MDS patients. CONCLUSIONS:
      These observations confirm thalidomide efficacy in myeloma, suggest a possible
      use in MDS and histiocytosis and may contribute to the prediction of clinical
      response and to understanding the mechanism of thalidomide's action.

PMID- 11521808
TI  - Thalidomide and dexamethasone combination for refractory multiple myeloma.
AB  - BACKGROUND: Thalidomide is effective in approximately 30% of patients with
      refractory multiple myeloma. Dexamethasone is active in 25% of patients with
      disease resistant to alkylating agents. We investigated the combination of
      thalidomide with dexamethasone as salvage treatment for heavily pretreated
      patients with multiple myeloma, in order to assess its efficacy and toxicity.
      PATIENTS AND METHODS: Forty-four patients with refractory myeloma were treated
      with thalidomide, 200 mg p.o. daily at bedtime, with dose escalation to 400 mg
      after 14 days, and dexamethasone, which was administered intermittently at a dose
      of 20 mg/m2 p.o. daily for four days on day 1-4, 9-12, 17-20, followed by monthly
      dexamethasone for four days. Patients' median age was 67 years. All patients were
      resistant to standard chemotherapy, 77% were resistant to dexamethasone-based
      regimens and 32% had previously received high-dose therapy. RESULTS: On an
      intention-to-treat basis twenty-four patients (55%) achieved a partial response
      with a median time to response of 1.3 months. The thalidomide and dexamethasone
      combination was equally effective in patients with or without prior resistance to
      dexamethasone-based regimens and in patients with or without prior high-dose
      therapy. Toxicities were mild or moderate and consisted primarily of
      constipation, morning somnolence, tremor, xerostomia and peripheral neuropathy.
      The median time to progression for responding patients is expected to exceed 10
      months and the median survival for all patients is 12.6 months. CONCLUSION: The
      combination of thalidomide with dexamethasone appears active in patients with
      refractory multiple myeloma. If this activity is confirmed, further studies of
      this combination as second-line treatment for patients resistant to conventional
      chemotherapy, and as primary treatment for patients with active myeloma, should
      be considered.

PMID- 11521810
TI  - Comments on model of biota-sediment accumulation factor for polycyclic aromatic
      hydrocarbons.

PMID- 11521809
TI  - Radiotherapy after breast-conserving surgery in small breast carcinoma: long-term
      results of a randomized trial.
AB  - BACKGROUND: Breast-conserving surgery followed by radiotherapy is a widely
      accepted form of treatment in patients with breast cancer of limited extent. Many
      attempts have been made to identify subgroups of patients who might avoid
      radiotherapy. PATIENTS AND METHODS: Between 1987 and 1989, 579 women with
      carcinoma of the breast were randomly assigned to quadrantectomy, axillary
      dissection and radiotherapy (299) and to quadrantectomy with axillary dissection
      without radiotherapy (280). Eligible patients were women with a breast carcinoma
      less than 2.5 cm in maximum diameter up to 70 years of age. Primary endpoints
      were intra-breast tumour reappearance (IBTR) and all-cause mortality. RESULTS:
      The number of IBTRs was significantly higher in patients treated with surgery
      alone (59 cases out of 273; 10-year crude cumulative incidence of 23.5%) than in
      patients treated with surgery plus radiotherapy (16 cases out of 294; 10-year
      crude cumulative incidence of 5.8%). The difference in IBTR frequency between the
      two treatments appeared to be particularly high in women up to 45 years of age,
      tending to decrease with increasing age up to no apparent difference in women
      older than 65 years. Overall survival curves for the two groups, did not differ
      significantly (P = 0.326). However, a limited survival advantage was evident
      after radiotherapy for node-positive women. CONCLUSIONS: After breast-conserving
      surgery radiotherapy appears indicated in all patients up to 55 years of age, in
      patients with positive axillary nodes, and in patients with extensive intraductal
      component at histology. The data suggest that radiotherapy may be avoided in
      patients older than 65, and may be optional in women aged 56-65 years with
      negative nodes.

PMID- 11521811
TI  - Identification and quantitation method for nonylphenol and lower oligomer
      nonylphenol ethoxylates in fish tissues.
AB  - Substantial research is currently focused on the toxicological effects of
      alkylphenol ethoxylates (APEs) and alkylphenols (APs) on aquatic animals.
      Considerable data are available on the concentrations of APEs and APs in river
      systems in the United States; however, few if any data are available on the
      tissue concentrations of fish living in these rivers. A reliable method for the
      analysis of nonylphenol (NP) and lower oligomer nonylphenol ethoxylates (NPE1-3)
      in fish tissues has been developed. Nonylphenol and NPE1-3 were extracted from
      fish tissues using extractive steam distillation. Normal phase high-performance
      liquid chromatography (HLPC) was used as a cleanup step prior to analysis by gas
      chromatography with mass selective detection (GC/MSD) using selected ion
      monitoring. Optimization of this technique resulted in consistent recoveries in
      excess of 70%, with the exception of NPE3 (17%). Method detection limits (MDLs)
      and limits of quantitation using the technique range from 3 to 20 and 5 to 29
      ng/g wet weight, respectively. Nonylphenol and NPE1 were detected in subsamples
      (n = 6) of a single common carp captured in the Las Vegas Bay of Lake Mead (NV,
      USA) at average concentrations of 184+/-4 ng/g and 242+/-9 wet weight,
      respectively. Nonylphenol ethoxylates were not detected in the carp collected at
      Lake Mead.

PMID- 11521812
TI  - Identification of hydroxylamino-dinitroso-1,3,5-triazine as a transient
      intermediate formed during the anaerobic biodegradation of hexahydro-1,3,5
      trinitro-1,3,5-triazine.
AB  - The metabolic fate of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) in a mixed
      culture incubated under methanogenic conditions was studied. Analysis by high
      performance liquid chromatography (HPLC) confirmed the loss of RDX and the
      formation of mono-, di-, and trinitroso-RDX as transient biodegradation
      intermediates. An additional peak observed in the HPLC chromatograms was
      identified by liquid chromatography-mass spectrometry as hydroxylamino-dinitroso
      1,3,5-triazine. This is the first report identifying hydroxylamino-dinitroso
      1,3,5-triazine as a transient intermediate produced during the anaerobic
      biodegradation of RDX.

PMID- 11521813
TI  - Polychlorinated naphthalenes, biphenyls, dibenzo-p-dioxins, and dibenzofurans as
      well as polycyclic aromatic hydrocarbons and alkylphenols in sediment from the
      Detroit and Rouge Rivers, Michigan, USA.
AB  - Sediment from the upper Detroit and lower Rouge Rivers in southeastern Michigan,
      USA, were analyzed to examine the distribution of polychlorinated naphthalenes
      (PCNs), biphenyls (PCBs), dibenzo-p-dioxins (PCDDs), and dibenzofurans (PCDFs) as
      well as polycyclic aromatic hydrocarbons (PAHs) and alkylphenolic compounds such
      as butylphenol, octylphenol, and nonylphenol (NP). Sediments from a non-point
      source location in Lake Michigan were also analyzed for target compounds.
      Concentrations of target compounds in the upper Detroit and lower Rouge Rivers
      varied considerably among locations, and notable spatial variation existed.
      Concentrations of PCNs and PCDDs/PCDFs in sediments from the upper Detroit and
      lower Rouge Rivers ranged from 0.08 to 187 ng/g and 69 to 1420 pg/g dry weight,
      respectively. Total PCBs, PAHs, and NP concentrations ranged from 8 to 25,000, 17
      to 44,000, and < 10 to 60,000 ng/g dry weight, respectively. Concentrations of
      all target compounds except PCNs were significantly correlated with total organic
      carbon content of sediments. Similarly, concentrations of PCBs, PCDDs, and PCDFs
      were significantly correlated with each other. The distribution of organic
      contaminants in the upper reaches of the Detroit River and lower Rouge River
      suggested the presence of localized, but multiple, sources of contamination for
      each compound class. Conners Creek combined sewer overflow has been identified as
      one of the potential sources for the upper Detroit River, where the highest
      concentrations PCBs and PCDDs/PCDFs were found. Polycyclic aromatic hydrocarbon
      and NP concentrations were consistently high in sediment from the lower Rouge
      River. Analysis of data from selected locations suggested that PCNs contributed a
      greater proportion of the dioxin-like activity than PCBs and PCDDs/PCDFs
      contributed.

PMID- 11521814
TI  - Benzo[a]pyrene and zinc solubilization by digestive fluids of benthic
      invertebrates--a cross-phyletic study.
AB  - Contaminant bioavailability via digestive exposure was examined for 18 species of
      marine benthic invertebrates, using incubation of digestive fluids with sediments
      that were spiked with either radiolabeled benzo-[a]-pyrene (BaP) or zinc.
      Interphyletic trends in contaminant solubilization were compared with measures of
      digestive biochemistry, including enzyme activities, surfactancy, pH, and fluid
      phase organic carbon, amino acids, and lipids. Contaminant solubilization ranged
      from values equal to that of a seawater control to as much as an order of
      magnitude higher but were lower than those obtained with commonly used chemical
      extractants. Digestive fluids from echinoderms and a cnidarian tended to be
      relatively weak, those from polychaetes and echiurans were relatively strong, and
      those from taxa such as sipunculans and mollusks were intermediate. These trends
      correlated strongly with concentrations or activities of digestive biochemicals
      but not with pH. These correlations are consistent with previous work on
      mechanisms of digestive solubilization of polycyclic aromatic hydrocarbons (PAH)
      and metals, though strong covariance among digestive parameters does not allow
      this approach to be used for identification of specific mechanism(s).

PMID- 11521815
TI  - Modeling zinc toxicity for terrestrial invertebrates.
AB  - Acute and chronic ecotoxicity tests with zinc were performed with the earthworm
      Eisenia fetida, the potworm Enchytraeus albidus, and the springtail Folsomia
      candida. To assess the influence of the soil type on zinc toxicity for these soil
      invertebrates, these tests were carried out in a standard artificial soil, a
      sandy and a loamy field soil. Based on the results of this experimental work and
      data taken from literature, models were developed relating the ecotoxicity of
      zinc to the most important parameters controlling bioavailability: pH and cation
      exchange capacity. Models were developed for E. fetida and F. candida using the
      regression technique partial least squares projection to latent structures (PLS).
      Acute as well as chronic toxicity data of both organisms could be normalized on
      the basis of the pH and the cation exchange capacity of the test soils. For other
      terrestrial invertebrates, not enough data were available to develop reliable
      models.

PMID- 11521816
TI  - Evaluating degradation rates of chlorinated organics in groundwater using
      analytical models.
AB  - The persistence and fate of organic contaminants in the environment largely
      depends on their rate of degradation. Most studies of degradation rate are
      performed in the lab where chemical conditions can be controlled precisely.
      Unfortunately, literature values for lab degradation studies often are orders of
      magnitude higher than for field-generated studies, calling into question the
      relevance of lab-generated values for characterizing the persistence of organic
      contaminants in the environment. Complicating analysis of this ostensible
      disparity between lab and field degradation values, field-generated values often
      do not account for effects of adsorption. Modeling with a newly derived
      analytical solution for first-order degradation coupled with advective losses and
      adsorption to solve for degradation constants is insensitive to uncertainties in
      field properties. Application to field data shows that accounting for advection
      and adsorption greatly affects the value of calculated degradation constants
      compared to disappearance constants, which do not account for these phenomena. In
      fact, degradation constants, calculated using these analytical solutions and
      field data, are in the range reported for lab-generated data. Using these
      analytical solutions, for the sulfate-reducing field conditions documented for
      this site, perchloroethene, trichloroethene, 1,1,1-trichloroethane, 1,1
      dichloroethane, and chloroethane all degraded with half-lives ranging from 5 to
      115 d. Consistent with other studies of sulfate-reducing conditions, cis-1,2
      dichloroethene did not chemically degrade at a measurable rate. When nonaqueous
      phase 1,1-dichloroethane is present, down-gradient concentrations vary in an
      annual sinusoidal pattern, apparently because of seasonal variation in dilution
      from groundwater recharge.

PMID- 11521817
TI  - Distribution, speciation, and bioavailability of lanthanides in the Rhine-Meuse
      estuary, The Netherlands.
AB  - Changing environmental conditions may influence the fate and bioavailability of
      lanthanides (part of the rare earth elements [Ln]) in estuaries. The aim of this
      study was to quantify the variation in estuarine lanthanide solid/water
      distribution, speciation, and bioaccumulation. The latter was studied in the
      amphipod Corophium volutator under field and laboratory conditions. Calculations
      with the chemical equilibrium model MINEQL+ indicate that dissolved lanthanides
      are complexed mainly to carbonates and dissolved organic matter. In the water
      phase, the relative abundance of the free ion, LnCO3, and humic complexes
      decreases from lanthanum to lutetium, whereas the relative abundance of Ln(CO3)2
      increases. Cerium and europium anomalies were found in the water. Europium
      anomalies were also found in some biota. The biota sediment accumulation factors
      (BSAFs) decreased across the series from lanthanum to lutetium. Regression
      analysis revealed that alkalinity correlated negatively with lanthanide uptake.
      This suggests that increasing complexation reduced bioavailability under the
      prevailing conditions. The BSAFs did not depend on salinity or pH, which may
      simplify sediment-quality criteria for fresh versus saline waters. Field BSAFs
      were significantly lower than laboratory values for the same sediments, which is
      explained by adaptation of the organisms to lanthanides.

PMID- 11521818
TI  - Accumulation of 137Cesium and 90Strontium from abiotic and biotic sources in
      rodents at Chornobyl, Ukraine.
AB  - Bank voles (Clethrionomys glareolus) and laboratory strains of house mice (Mus
      musculus BALB and C57BL) were relocated into enclosures in a highly contaminated
      area of the Red Forest near the Chornobyl (Ukraine) Reactor 4 to evaluate the
      uptake rates of 137Cs and 90Sr from abiotic sources. Mice were provided with
      uncontaminated food supplies, ensuring that uptake of radionuclides was through
      soil ingestion, inhalation, or water. Mice were sampled before introduction and
      were reanalyzed every 10 d for 137Cs uptake. Levels of 90Sr were assessed in
      subsamples from the native populations and in experimental animals at the
      termination of the study. Uptake rates in house mice were greater than those in
      voles for both 137Cs and 90Sr. Daily uptake rates in house mice were estimated at
      2.72 x 10(12) unstable atoms per gram (whole body) for 137Cs and 4.04 x 10(10)
      unstable atoms per gram for 90Sr. Comparable rates in voles were 2.26 x 10(11)
      unstable atoms per gram for 137Cs and 1.94 x 10(10) unstable atoms per gram for
      90Sr. By comparing values from voles in the enclosures to those from wild voles
      caught within 50 m of the enclosures, it was estimated that only 8.5% of 137Cs
      was incorporated from abiotic sources, leaving 91.5% being incorporated by uptake
      from biotic materials. The fraction of 90Sr uptake from abiotic sources was at
      least 66.7% (and was probably much higher). Accumulated whole-body doses during
      the enclosure periods were estimated as 174 mGy from intramuscular 137Cs and 68
      mGy by skeletal 90Sr in house mice over 40 d and 98 mGy from 137Cs and 19 mGy
      from 90Sr in voles over 30 d. Thus, uptake of radionuclides from abiotic
      materials in the Red Forest at Chornobyl is an important source of internal
      contamination.

PMID- 11521819
TI  - Experimental exposure of naive bank voles (Clethrionomys glareolus) to the
      Chornobyl, Ukraine, environment: a test of radioresistance.
AB  - Previous studies have demonstrated no difference in micronucleus (MN) frequencies
      between wild rodents chronically exposed to the environmental radiation
      contamination of the Chornobyl (Ukraine) exclusion zone and those inhabiting
      reference populations. The aim of the present study was to test the hypothesis
      that a population of bank voles (Clethrionomys glareolus) has developed
      radioresistance as a result of 14 years of chronic, low-dose radiation exposure.
      Naive voles were placed in environmental enclosures in the Red Forest region of
      the exclusion zone for 30 d. Blood samples were obtained at regular intervals,
      and the MN assay was used to assess chromosomal damage. Additionally,
      radionuclide uptake was monitored throughout the study, and dose was documented
      for each individual as well as for their offspring. Total dose for the voles
      experimentally exposed in this environment averaged 1.09 Gy (36.20 mGy d(-1)) for
      the 30-d study period. Our results indicate that exposure to radiation levels
      well above regulatory statutes did not result in an increased MN frequency.
      Furthermore, our results do not support the hypothesis that voles chronically
      exposed to these radiation levels have developed a genetic basis for
      radioresistance that is unique from that present in naive populations. The use of
      C. glareolus as a sentinel species for environmental studies of radiation
      contamination and the question of whether the MN assay is an appropriate endpoint
      for studies of low-dose, chronic radiation exposure are also discussed.

PMID- 11521820
TI  - Persistence of the effects of Jet-A in a microcosm with releases from the
      sediment.
AB  - This study investigates both the methods and the multispecies and functional
      level effects of a release of a complex hydrocarbon mixture from sediments using
      a 60-d modified mixed flask culture (MFC) microcosm. Neat Jet-A was injected and
      mixed into the sediment with one nondosed and three dosed concentrations.
      Univariate and multivariate statistical and graphical techniques were used to
      detect patterns in the data. A slow release of the test material from the spiked
      sediment layer was obtained, and constituents of Jet-A were detected. Functional
      parameters (such as pH) were generally better at determining treatment groups
      than structural parameters (population densities). Analysis of the ability of the
      various parameters to detect treatment differences confirms that there is not one
      best indicator for the status of an ecological structure. Transient but
      statistically significant outcomes were seen at initial treatment concentrations
      as low as 2 microl/L. The higher concentration treatment groups could be
      identified as distinguished from nondosed or lower treatments at the end of the
      63-d experiment. Each of the three multivariate techniques differed in their
      ability to distinguish treatment groups during the course of the experiment.

PMID- 11521821
TI  - The garden snail (Helix aspersa) as a bioindicator of organophosphorus exposure:
      effects of dimethoate on survival, growth, and acetylcholinesterase activity.
AB  - The garden snail (Helix aspersa) is currently used as bioindicator of metallic
      pollution. Our objective was to extend its use to organic chemicals by studying
      the effects and tissue concentrations of the organophosphorus pesticide
      dimethoate following dietary uptake. After exposure for four weeks to increasing
      doses of pesticide in the diet, the median lethal concentration (LC50) was
      determined to be 3,700 microg/g food. Clinical signs indicated a no-observed
      effect concentration of 100 microg/g and a lowest-observed-effect concentration
      of 250 microg/g. The growth parameters were decreased with increasing exposure to
      the pesticide. The median effective concentration (EC50), which was evaluated
      based on both shell diameter and dry weight inhibitions, was 665 and 424
      microg/g, respectively, and the EC10 was 180 and 145 microg/g, respectively.
      Accumulation in the viscera was related to the amount of dimethoate in the food.
      The bioconcentration factors were low (>6 x 10(-3)). Acetylcholinesterase (AChE)
      activity was strongly decreased (80% from 250 microg/g). In conclusion, we
      demonstrated that the species H. aspersa could be a useful sentinel organism for
      organophosphorus contamination surveys. Among the effects measured, the
      inhibition of AChE activities and clinical signs were the most sensitive,
      followed by the growth parameters. These results confirm the suitability of the
      garden snail for development of sublethal toxicity tests using primary consumers
      and aboveground organisms.

PMID- 11521822
TI  - Assessing the potential for pesticide leaching for the pine forest areas of
      Tenerife.
AB  - Currently, no guidelines cover use of pesticides in the forested areas of the
      Canary island of Tenerife. An index-based model (Li) was used to rank the
      leaching potential of 50 pesticides that are, or could be, used for management
      purposes in the pine forest areas of Tenerife. Once the pesticides with the
      greatest leaching potential were identified, regional-scale groundwater
      vulnerability assessments, with consideration for data uncertainties, were
      generated using soil, climatic, and chemical information in a geographic
      information system framework for all pine forest areas of the island. Process
      based simulations with the pesticide root zone model for the areas and pesticides
      of highest vulnerability were conducted to quantitatively characterize the
      leaching potentials. Carbofuran, hexazinone, picloram, tebuthiuron, and triclopyr
      were each identified as being potential leachers.

PMID- 11521824
TI  - Vitellogenin gene transcription: a relative quantitative exposure indicator of
      environmental estrogens.
AB  - We report the development of a quantifiable exposure indicator for measuring the
      presence of environmental estrogens in aquatic systems. Synthetic
      oligonucleotides, designed specifically for the vitellogenin gene (Vg)
      transcription product, were used in a reverse transcription-polymerase chain
      reaction (RT-PCR) protocol. This extremely sensitive and rapid method was able to
      detect vitellogenin gene transcription in male common carp (Cyprinus carpio)
      injected with 17beta-estradiol. Sequence analysis of the induced mRNA product
      confirmed a vitellogenin gene transcript with homology to rainbow trout and
      fathead minnow vitellogenin cDNA sequences. Relative levels of vitellogenin gene
      induction among individuals were quantified by incorporating 18S ribosomal RNA
      universal primers and Competimers in a PCR multiplex reaction with primers for
      vitellogenin. This method is more sensitive than current protocols, such as
      mortality, visible signs of stress, or other techniques that look for unscheduled
      gene expression, because it measures the appearance of primary transcripts at the
      nanogram level. In addition, this procedure does not sacrifice accuracy or
      reliability, even though the exposure to estrogen is within 1 d. This research
      will support the construction of regional stressor profiles, thereby providing a
      method for comparative environmental exposure assessment. It may also provide an
      in vivo screening method for potential endocrine-disrupting compounds.

PMID- 11521823
TI  - The sheepshead minnow as an in vivo model for endocrine disruption in marine
      teleosts: a partial life-cycle test with 17alpha-ethynylestradiol.
AB  - The sheepshead minnow (Cyprinodon variegatus Lacepede), an estuarine fish
      species, was exposed to 17alpha-ethynylestradiol (EE2) at nominal test
      concentrations of 0.2, 2, 20, 200, 400, 800, 1,600, and 3,200 ng/L. Fish were
      exposed for up to 59 d, from subadult stages to sexual maturity, under flow
      through conditions. The exposure period was followed by an evaluation of
      reproductive success and survival of progeny. The reproductive success of exposed
      sheepshead minnows, as determined from data on egg production from two subsequent
      spawning trials, was reduced in fish exposed to 200 ng/L EE2 and, in one spawning
      trial, in the 20-ng/L treatment. Hatching success was reduced in the progeny of
      fish exposed to 200 ng/L EE2, but survival was good among fry that successfully
      hatched. Histological examination indicated generalized edema, damage to gill
      epithelia, hepatic toxicity, fibrosis of the testis, and evidence of sex
      reversal, including testes-ova and spermatagonia-like cells in ovaries. The
      maximum acceptable toxicant concentration (MATC) for gonadal development in males
      was within the normal range of EE2 concentrations in sewage treatment plant
      effluents. The exposure regimen and choice of test organism, combined with
      histological examination, allowed independent evaluation of ecologically
      significant acute, reproductive and estrogenic endpoints. Estrogen receptor
      mediated effects occurred at concentrations where reproductive effects were
      measurable under standard reproduction assays. The sheepshead minnow appears to
      be a sensitive in vivo model for partial life-cycle testing of compounds that
      have the potential to disrupt the endocrine system as well as reproduction in
      estuarine and coastal marine fish species.

PMID- 11521825
TI  - Natural exposure of coastal river otters to mercury: relation to age, diet, and
      survival.
AB  - We evaluated effects of location (i.e., Jackpot Bay, a naturally contaminated
      site, and Herring Bay, reference site), diet as determined by stable isotopes,
      and age on mercury concentrations in individual river otters (Lontra canadensis)
      from Prince William Sound, Alaska, USA. We also investigated the effects of
      mercury accumulation on survival of river otters from these two locations. Our
      results indicated that mercury concentrations in fishes from Jackpot Bay were
      significantly higher than those in fishes from Herring Bay and those in pelagic
      fishes. In addition, a predominant intertidal fish diet in both areas influenced
      the accumulation of mercury concentrations in otters. Concentrations of mercury
      in fur of river otters from Jackpot Bay were significantly higher than those of
      animals from Herring Bay. Nonetheless, we did not detect significant differences
      in survival between otters inhabiting the two areas, suggesting that this natural
      contamination was not high enough to impair survival. Our ability to investigate
      the effects of various factors such as location, diet composition, and age on
      mercury accumulation and subsequent survival of individuals offers an example for
      a link between individual-based captive studies and population-level field
      investigations.

PMID- 11521826
TI  - Life history and spatial distribution of the enchytraeid worm Cognettia
      sphagnetorum (Oligochaeta) in metal-polluted soil: below-ground sink-source
      population dynamics?
AB  - We studied the life history, metal-avoidance behavior, spatial distribution, and
      population growth of enchytraeid worms (Cognettia sphagnetorum [Oligochaeta])
      originating from two sites: one uncontaminated, and another patchily polluted by
      heavy metals. Effects of patchy soil contamination on populations were studied in
      microcosms. In uncontaminated soil, worms from the polluted site had lower
      viability and reduced growth rate as juveniles but higher growth rate as adults
      compared to worms from the unpolluted site. They were also smaller in size at
      fragmentation (reproduction). Worms from the polluted site reached a larger
      population size than worms from the unpolluted site. Hence, worms from the
      polluted site seemed to allocate more energy to reproduction, because such a
      strategy can be highly adaptive when living in a less-polluted patch (the source)
      in, on average, a highly polluted environment. The C. sphagnetorum actively
      avoided Cu-contaminated soil, with the response being stronger in individuals
      from the contaminated site. When an unpolluted patch (the source) was surrounded
      by a toxic environment (the sink), worms were found in the sink, either because
      intraspecific competition overrode the avoidance behavior or because of random
      walk migration. As a result, total population size in these microcosms were as
      high as those in totally uncontaminated microcosms. Our results indicate that
      avoidance behavior and increased allocation to reproduction, together with the
      observed dispersal pattern, can be an adaptive strategy for C. sphagnetorum in
      the presence of small, less-polluted patches in, on average, a hostile
      environment. Hence, sink-source population regulation can explain spatial
      distribution and survival of C. sphagnetorum in patchily polluted field soils.
      When such population dynamics occur, this pattern should be taken into account
      when population densities in the field are monitored for ecological risk
      assessment procedures concerning toxicants.

PMID- 11521827
TI  - Effects of terbutryn on aufwuchs and Lumbriculus variegatus in artificial indoor
      streams.
AB  - The effects of the herbicide terbutryn on a simple lotic food web were
      investigated during a 72-d exposure period in five artificial indoor streams in a
      greenhouse. The model compound terbutryn, an s-triazine and an inhibitor of
      photosynthesis, was applied once in each stream at nominal concentrations of 0.6,
      6, 60, or 600 microg/L. Terbutryn concentrations in the water were analyzed by
      gas chromatography/mass spectrometry, and an overall time to 50% dissipation
      (DT50) of 28 d was calculated. The development of aufwuchs and the population
      growth and development of the oligochaete Lumbriculus variegatus were
      investigated. We determined that terbutryn was toxic to L. variegatus at 23.7
      mg/L (96-h median lethal concentration [LC50]) and 16.5 mg/L (96-h median
      effective concentration [EC50]) in static acute toxicity tests. Terbutryn
      decreased aufwuchs production at 0.6 microg/L in the experimental streams.
      Population growth of L. variegatus was decreased by 50% at 6 microg/L. The effect
      of terbutryn on the aufwuchs was a direct effect of decreases in the periphyton.
      However, the effects on L. variegatus were an indirect effect of terbutryn as a
      consequence of decrease in the aufwuchs food source and occurred at three-orders
      of-magnitude-lower concentrations of terbutryn than the acute toxicity effects.
      Our study demonstrates the utility of indoor lotic microcosm studies for
      evaluating both direct and indirect effects of contaminants on aquatic
      ecosystems.

PMID- 11521828
TI  - The use of carbamates, atropine, and 2-pyridine aldoxime methoiodide in the
      protection of Artemia salina against poisoning by carbophenothion.
AB  - The acute toxicity of carbophenothion to three age classes of Artemia salina was
      evaluated. An increase in toxicity of carbophenothion was found following longer
      development of A. salina. The effect of pretreatment with the nonselective
      muscarinic antagonist atropine, the two reversible acetylcholinesterase
      inhibitors physostigmine and pyridostigmine, and the cholinesterase-reactivating
      oxime 2-pyridine aldoxime methochloride (2-PAM) on carbophenothion-induced
      lethality in 24-h-old A. salina was also investigated. The lethal action of
      carbophenothion was completely prevented by pretreatment of A. salina with 2-PAM.
      Atropine and pyridostigmine afforded a maximal protection of approximately 87%
      and 72%, respectively, compared to control values. In contrast, physostigmine was
      ineffective. The inhibitory effects of combinations of 10(-5) M atropine with
      physostigmine, pyridostigmine, or 2-PAM were greater than those elicited by
      either drug alone, with the maximum protection afforded being 92.58%, 100%, and
      100%, respectively. In the presence of 10(-7) M atropine, neither pyridostigmine
      nor 2-PAM provided additional inhibition of the lethality compared to that with
      either drug alone, whereas the protection afforded by 10(-7) M atropine plus
      physostigmine increased as the concentration of carbamate increased (up to 10(-3)
      M). Pretreatment with pyridostigmine or physostigmine plus 2-PAM (10(-6) M)
      slightly enhanced the maximal inhibition of carbophenothion lethality compared to
      that with either drug alone. It is suggested that the most active combined
      pretreatment studied here was physostigmine plus atropine.

PMID- 11521829
TI  - Chemical and biological availability of sediment-sorbed benzo[a]pyrene and
      hexachlorobiphenyl.
AB  - This study examined the chemical and biological availability of two nonpolar
      organic compounds, benzo[a]pyrene (BaP) and hexachlorobiphenyl (HCBP), from a
      spiked sediment that was aged for varying amounts of time. Chemical availability
      was evaluated using four different solvent combinations to extract chemicals from
      the sediment. The extractability of BaP and HCBP from sediment using traditional
      solvents was then compared to the transfer efficiency (TE) of a benthic
      invertebrate (Lumbriculus variegatus) to relate chemical extractability to
      bioavailability in the organisms. Results indicated that water was the solvent
      that best approximated bioavailability for BaP, whereas comparisons for HCBP were
      inappropriate, because TE values exceeded 100%. The inability to obtain a
      reasonable TE estimate for HCBP was most likely due to the fact that the
      oligochaetes received a major portion of their uptake from interstitial water
      instead of ingestion of sediment particles, which invalidated an important
      assumption of the TE model. Overall, the results of this study indicate that
      exhaustive chemical extractions may be an inaccurate representation of the
      bioavailable fractions for some contaminants.

PMID- 11521830
TI  - Phototoxicity of anthracene and pyrene to glochidia of the freshwater mussel
      Utterbackia imbecillis.
AB  - The acute toxicity of photoactivated anthracene and pyrene to the glochidial
      larvae of the paper pondshell (Utterbackia imbecillis) was characterized in the
      laboratory using two sets of experiments. Acute toxicity tests designed to
      determine the overall sensitivity of glochidia to anthracene and pyrene were
      conducted under simulated sunlight (ultraviolet [UV]-A = 70+/-0.5 microW/cm2
      [mean +/- standard deviation]). The median lethal concentration (LC50) and median
      lethal dose (LD50) of anthracene at 24 h were 1.93 (95% CI, 0.87-3.02) microg/L
      and 1.94 (1.87-2.00) microg/g glochidia, respectively. The LC50 and LD50 for
      pyrene at 24 h were 2.63 (2.38-2.90) microg/L and 6.36 (5.82-6.94) microg/g
      glochidia, respectively. Acute toxicity tests designed to delineate the
      relationship between the rate of mortality and UV intensity were conducted under
      one of four different UV intensities (UV-A = 15, 31, 50, and 68 microW/cm2).
      Regression analyses revealed that time to death decreased as tissue residue
      concentrations and UV intensity increased for both compounds. Based on measured
      tissue residues, anthracene was 1.5-fold more potent than pyrene and 3-fold more
      potent than fluoranthene. The lower potency of fluoranthene is in agreement with
      previously developed structure-activity relationships; however, these
      relationships predict equal potency between anthracene and pyrene. These findings
      suggest that glochidia of freshwater mussels are sensitive to photoactivated
      anthracene and pyrene at environmentally relevant concentrations, that the time
      dependent mortality of glochidia can be accurately predicted through evaluating
      the product of tissue residue and light intensity, and that species-dependent
      factors may alter the predicted relative potencies of anthracene and pyrene.

PMID- 11521831
TI  - Linking ecological impact to metal concentrations and speciation: a microcosm
      experiment using a salt marsh meiofaunal community.
AB  - Microcosm experiments addressed the impact of a mixture of Cu, Cr, Cd, Pb, and Hg
      at three concentrations after 36 h, 12 d, and 30 d on a meiofauna-dominated salt
      marsh community. In addition to analyzing effects on meiofaunal abundances, the
      study quantified the sediment metal concentrations of all five metals and pore
      water concentrations, speciation, and ligand complexation of Cu. Abundances of
      deposit feeders such as the polychaete Streblospio benedicti, gastropods, and
      bivalves were impacted at lower metal concentrations than the mainly algal
      feeding copepods, ostracods, and nematodes. We suggest that this might be due to
      bulk ingestion of metal-contaminated sediments resulting in relatively higher
      metal exposure in the deposit feeders than in the other, nondeposit feeding taxa.
      Copepod and ostracod abundances decreased only in the highest metal treatment,
      where levels of inorganic Cu ([Cu']) in pore waters were similar to levels
      associated with both acute and subacute toxicity in published in vivo toxicity
      studies of marine copepods. The higher metal treatments yielded
      disproportionately higher pore-water [Cu] compared with sediment [Cu], suggesting
      saturation of sediment-associated ligands with increased additions of Cu.
      Similarly, the higher metal treatments appeared to reach saturation of the
      organic Cu ligands, with the excess pore-water [Cu] present in the more toxic,
      inorganic species of Cu. Acid-volatile sulfide (AVS) concentrations at sediment
      horizons inhabited by meiofauna were low and AVS was not considered a significant
      metal ligand at these depths. Since meiofauna are predominantly associated with
      oxic surface sediments, it is doubtful that AVS is a major factor controlling
      availability of free metal for exposure to these taxa.

PMID- 11521832
TI  - Screening of environmental contaminants for ecdysteroid agonist and antagonist
      activity using the Drosophila melanogaster B(II) cell in vitro assay.
AB  - The B(II) bioassay was developed as a rapid and reliable tool for detecting
      potential insect growth regulators acting as ecdysteroid receptor (ant)agonists.
      Based on an ecdysteroid-responsive cell line from Drosophila melanogaster, this
      microplate assay is ideally suited to the evaluation of environmental
      contaminants as potential endocrine disrupters. Data are presented for about 80
      potential environmental contaminants, including industrial chemicals, pesticides,
      pharmaceuticals, phytoestrogens, and vertebrate steroids, and are compared with
      data for known (ant)agonists. Apart from androst-4-ene-3,17-dione (a weak
      antagonist), vertebrate steroids were inactive at concentrations up to 10(-3) M.
      The vast majority of xenobiotics also showed no (ant)agonist activity. Among the
      industrial chemicals, antagonistic activity was observed for bisphenol A median
      effective concentration (EC50) of 1.0 x 10(-4) M and diethylphthalate (EC50 of
      2.0 x 10(-3) M). Some organochlorine compounds also showed weak antagonistic
      activity, including o,p'-dichlorodiphenyldichloroethylene (DDE), p,p'-DDE,
      dieldrin, and lindane (EC50 of 3.0 x 10(-5) M). For lindane, bisphenol A, and
      diethylphthalate, activity is not associated with impurities in the samples and,
      for lindane and bisphenol A at least, the compounds are able to compete with
      ecdysteroids for the ligand binding site on the receptor complex, albeit at
      concentrations very much higher than those found in the environment. The only
      pharmaceutical showing any detectable antagonist activity was 17alpha
      ethynylestradiol. In the context of recent publications on potential endocrine
      disruption in marine and freshwater arthropods, these findings suggest that, for
      some compounds (e.g., diethylstilbestrol), ecdysteroid receptor-mediated
      responses are unlikely to be involved in producing chronic effects. The B(II)
      assay has a potentially valuable role to play in distinguishing between endocrine
      mediated, which normally occur at submicromolar concentrations, and
      pharmacological effects in insects and crustaceans.

PMID- 11521833
TI  - Plant-facilitated mobilization and translocation of weathered 2,2-bis(p
      chlorophenyl)-1,1-dichloroethylene (p,p'-DDE) from an agricultural soil.
AB  - Field experiments were conducted to determine the uptake and translocation of
      highly weathered 2,2-bis(p-chlorophenyl)1,1-dichloroethylene (p,p'-DDE) from an
      agricultural soil. In soil containing known amounts of p,p'-DDE, experimental
      plots containing zucchini, pumpkin, or spinach were constructed. At destructive
      harvest, three soil fractions were collected that differed in the degree of
      influence exerted by the plant roots. The bulk soil was vegetation-free, the near
      root zone was within the area encompassed by the roots, and the rhizosphere
      remained physically attached to the roots at harvest. For each crop,
      statistically significant decreases were found in the concentration of p,p'-DDE
      in either the near-root zone or the rhizosphere relative to the bulk soil,
      suggesting plant-facilitated mobilization and/or degradation of the residue.
      Plant tissues were analyzed to determine the extent of contaminant removal from
      the soil and the magnitude of translocation through the shoot system. The
      concentration of p,p'-DDE in the roots of both zucchini and pumpkin was more than
      an order of magnitude larger than the bulk soil concentration, followed by
      significant translocation through the plant tissues to the fruit. The data
      indicate that certain plants may effectively accumulate residues of persistent
      organic pollutants in their tissues, suggesting phytoremediation as a possible
      treatment strategy.

PMID- 11521834
TI  - Multigeneration zinc acclimation and tolerance in Daphnia magna: implications for
      water-quality guidelines and ecological risk assessment.
AB  - Development of zinc tolerance is described for the cladoceran Daphnia magna
      Straus. Zinc tolerance (i.e., toxicity and deficiency) was monitored during
      successive generations of D. magna acclimated to different zinc concentrations.
      Survival, reproduction, carapax length measurements, and cellular energy
      allocation assessments were used as test endpoints. Special attention was paid to
      the consequences of zinc deficiency. The zinc acclimation concentration clearly
      influenced the overall fitness of the organism. After several generations of
      acclimation, an optimal concentration curve was observed, with an optimum zinc
      concentration between 300 and 450 microg/L. Zinc deficiency resulted in a lower
      zinc tolerance, a higher coefficient of variation for brood size, and an
      increased pH sensitivity. These results clearly indicate that (background) zinc
      concentrations present in test and culture media have to be considered in the
      evaluation of toxicity test results, especially when the toxicity data are used
      for water-quality guideline derivation and/or ecological risk assessment. Culture
      and test media containing very little or no zinc do not provide a basis for
      useful ecotoxicological data.

PMID- 11521835
TI  - Class III metallothioneins in response to cadmium toxicity in the marine
      microalga Tetraselmis suecica (Kylin) Butch.
AB  - Microalgae are one of the most important organisms in our ecosystems being
      seriously affected by metal pollution. However, the microalgae Tetraselmis
      suecica (Kylin) Butch is tolerant to cadmium; the concentration of this metal
      that reduces the population growth to 50% of the control growth level is 5.8 mg/L
      after 96 h of exposure. In this study, class III metallothioneins were
      investigated for their involvement as a possible tolerance mechanism in this
      microalga when exposed to cadmium. A set of these molecules was purified from
      these microalgal cells after exposure to the metal. These polypeptides were
      analyzed by capillary zone electrophoresis, which is a technique that allows the
      length of the metallothioneins synthesized by this microalga to be known. The T.
      suecica cells were able to synthesize class III metallothioneins of three to six
      subunits of (gamma-Glu-Cys). The most abundant polypeptide possessed four
      subunits, and (gamma-Glu-Cys)6-Gly was the largest polypeptide synthesized by
      this microalga and detected by this technique. Tolerance to cadmium as a function
      of increasing polypeptide length is also discussed.

PMID- 11521836
TI  - Zinc and cadmium body burdens in terrestrial oligochaetes: use and significance
      in environmental risk assessment.
AB  - Uptake and elimination kinetics of zinc and cadmium were studied in the
      oligochaetes Enchytraeus albidus and Eisenia fetida. Even at the highest exposure
      concentrations where E. fetida survived, the internal zinc concentration was
      still regulated to a constant level. Enchytraeus albidus could not regulate the
      internal zinc concentration as well, and the body burden increased after exposure
      to high zinc concentrations. After transfer to clean soil, the internal zinc
      concentration dropped back to the control level within a few weeks. For both
      species, internal cadmium concentrations did not reach equilibrium during the
      uptake experiments. The internal concentrations causing 50% reduction in cocoon
      production for E. fetida exposed to cadmium varied between different soil types,
      indicating that no fixed critical body burdens exist. For both zinc and cadmium,
      bioaccumulation factors decreased with increasing soil metal concentrations.
      Bioaccumulation factors may therefore be poor indicators of environmental risk.
      Their dependence on the total soil concentration makes bioaccumulation factors
      also unsuitable for assessing the influence of soil characteristics on the
      bioavailability of metals in contaminated field soils. For the same reason,
      uptake rate constants are probably not suited for this purpose.

PMID- 11521837
TI  - How water oxygenation level influences cadmium accumulation pattern in the
      Asiatic clam Corbicula fluminea: a laboratory and field study.
AB  - The level of O2 in water is highly variable in the aquatic environment and is a
      major ventilatory drive in all animals breathing water. Low O2 partial pressure
      (PO2) strongly stimulates ventilatory activity compared to air-equilibrated or O2
      enriched water. We studied the influence of ventilatory activity on the
      bioaccumulation rate of Cd in the freshwater Asiatic clam Corbicula fluminea for
      PO2 ranging from 4 to 40 kPa (2-20 mg/L at 15 degrees C) during steady-state
      exposure to controlled concentrations of Cd of approximately 2 or 0.5 microg/L
      under both laboratory and field conditions. The concentration of Cd in the
      expired water and its apparent extraction coefficient (EwCd) from the ventilated
      water were calculated. Results show that a low PO2 strongly enhanced Cd
      bioaccumulation rate in the whole soft body and modified the distribution pattern
      and the relative burden in the organs. Whatever the water PO2, values for the
      concentration of Cd in the expired water remained close to the Cd concentration
      in the inspired water and EwCd varied from 2 to 12%. Because the field results
      conformed to the laboratory analysis, the suggestion is made that the influence
      of O2 on bioaccumulation patterns of metals in water-breathers should be
      classified as of primary importance.

PMID- 11521838
TI  - An interlaboratory study on the use of steroid hormones in examining endocrine
      disruption.
AB  - In recent years, there has been an increased use of the measurement of sex
      steroid hormone levels in the blood of animals exposed to chemicals as an
      indicator of reproductive impairment or an alteration in endocrine function.
      Although levels of hormones are often compared among animals and laboratories,
      there has been no study to examine the between-laboratory variability in actual
      steroid measurements. Therefore, we initiated a study with white sucker collected
      from a site receiving pulp mill effluent, previously documented as having reduced
      steroid levels, to address this issue. Samples of plasma and media from in vitro
      gonadal incubations were delivered to eight outside laboratories with the ability
      to measure steroid hormones. These laboratories ranged from well-established fish
      endocrine laboratories to wildlife toxicology laboratories, which have recently
      implemented the methods to measure steroid hormones. In this study, we have
      considered both the absolute measure of steroid content between laboratories as
      well as the ability to discriminate between reference and exposed populations as
      important criteria when evaluating the utility of these measures. Of the eight
      outside laboratories conducting the analyses, six detected identical site
      differences in circulating levels of testosterone and 17beta-estradiol to those
      documented by our Burlington laboratory (ON, Canada). However, the absolute value
      of the steroid hormones measured in the plasma varied significantly (plasma
      testosterone 0.6-23.1 ng/ml, 17beta-estradiol 77.6-1782.7 pg/ml) with
      coefficients of variation of 70.4% and 60.3% respectively. Similar results were
      demonstrated for the measurement of steroid hormones in media following in vitro
      gonadal incubation. Although there was a fair amount of variability in the
      absolute measure of steroid hormone levels, we would predict a far greater
      coherence of interlaboratory results through the sharing of reagents and the use
      of a common methodology between laboratories. These results are very promising,
      providing evidence for the inclusion of steroid hormones in monitoring endocrine
      disruption in wildlife species.

PMID- 11521839
TI  - Combined effects of ultraviolet-B radiation and food shortage on the sensitivity
      of the Antarctic amphipod Paramoera walkeri to copper.
AB  - Investigations on the combined effects of ultraviolet (UV)-B radiation and
      anthropogenic toxicants have focused primarily on the chemical interactions
      between UV-B and organic compounds. Only a few studies have examined whether
      exposure to UV-B changes sensitivity to toxicants. This question is addressed in
      a laboratory study using the common shoreline Antarctic amphipod Paramoera
      walkeri and exposure to environmentally realistic levels of copper, UV-B
      radiation, and food shortage. Exposure to copper for 21 d in the absence of any
      additional stressors (food present, no UV-B) showed a lowest observable effective
      concentration (LOEC) of greater than 100 microg Cu/L. Exposure to copper and UV-B
      in combination, with no shortage of food, resulted in a LOEC of 45 microg Cu/L.
      When exposed to copper and UV-B, with shortage of food, a LOEC of 3 microg Cu/L
      was recorded. Hence, the combination of environmental stress from exposure to UV
      B radiation and shortage of food increases the sensitivity of P. walkeri to
      copper more than 30-fold. Increased metabolic energy requirements for defense
      mechanisms in response to toxicants and UV-B are discussed as possible
      explanations. It is concluded that consideration of environmental stressors in
      combination with toxicants increases the accuracy of ecological risk assessments
      of toxicants and should be part of the process for developing guidelines for
      ecologically acceptable concentrations of contaminants in the environment.

PMID- 11521840
TI  - Characterization of salinity-enhanced toxicity of aldicarb to Japanese medaka:
      sexual and developmental differences.
AB  - The effects of salinity, gender, and development on the acute toxicity of
      aldicarb were examined in the euryhaline fish, Japanese medaka (Oryzias latipes).
      The 96-h median lethal concentrations (LC50s) at 1.5 parts per thousand (per
      thousand) salinity were not significantly different between adults and juveniles
      but larvae were significantly more sensitive to aldicarb. A two-week exposure to
      increased salinity significantly enhanced the toxicity of 0.5 ppm aldicarb to
      both sexually mature male and female medaka. After 48 h of aldicarb exposure,
      mortality significantly increased (p < 0.05) in males from 13+/-5.7% at 1.5 per
      thousand, salinity to 56+/-5.7% at 20 per thousand; in females mortality
      significantly increased (p < 0.01) from 17+/-5.7% to 76+/-5.6%. A time-course
      study was conducted in which muscle acetylcholinesterase (AChE) inhibition was
      monitored after exposure to aldicarb. In general, AChE in females was inhibited
      to a greater degree at 12.0 and 20.0 per thousand salinity regimens than AChE in
      males. Muscle AChE in females residing at 20.0 per thousand was inhibited 93+/
      3.3% by 8 h of exposure to 0.95 ppm aldicarb, whereas in males the maximum
      inhibition was 80+/-7.4% after 8 h of exposure to 0.86 ppm aldicarb at 20 per
      thousand salinity. These results indicate that environmental factors, such as
      salinity, in addition to gender and development, have significant impacts on the
      acute toxicity of aldicarb to Japanese medaka.

PMID- 11521841
TI  - Mercury contamination and growth rate in two piscivore populations.
AB  - We found no relationship between fish growth rate and mercury concentration in a
      lake trout population and conditional support for an inverse relationship in a
      smallmouth bass population. A bioenergetics model indicated that mercury
      concentration was more responsive to dietary mercury intake than to growth rate.
      When biodilution is evident, it may bias contaminant versus fish size
      relationships.

PMID- 11521842
TI  - Application of a sigmapolycyclic aromatic hydrocarbon model and a logistic
      regression model to sediment toxicity data based on a species-specific, water
      only LC50 toxic unit for Hyalella azteca.
AB  - Two models, a sigmapolycyclic aromatic hydrocarbon (PAH) model based on
      equilibrium partitioning theory and a logistic-regression model, were developed
      and evaluated to predict sediment-associated PAH toxicity to Hyalella azteca. A
      sigmaPAH model was applied to freshwater sediments. This study is the first
      attempt to use a sigmaPAH model based on water-only, median lethal concentration
      (LC50) toxic unit (TU) values for sediment-associated PAH mixtures and its
      application to freshwater sediments. To predict the toxicity (i.e., mortality)
      from contaminated sediments to H. azteca, an interstitial water TU, calculated as
      the ambient interstitial water concentration divided by the water-only LC50 in
      which the interstitial water concentrations were predicted by equilibrium
      partitioning theory, was used. Assuming additive toxicity for PAH, the sum of TUs
      was calculated to predict the total toxicity of PAH mixtures in sediments. The
      sigmaPAH model was developed from 10- and 14-d H. azteca water-only LC50 values.
      To obtain estimates of LC50 values for a wide range of PAHs, a quantitative
      structure-activity relationship (QSAR) model (log LC50 - log Kow) with a constant
      slope was derived using the time-variable LC50 values for four PAH congeners. The
      logistic-regression model was derived to assess the concentration-response
      relationship for field sediments, which showed that 1.3 (0.6-3.9) TU were
      required for a 50% probability that a sediment was toxic. The logistic-regression
      model reflects both the effects of co-occurring contaminants (i.e., nonmeasured
      PAH and unknown pollutants) and the overestimation of exposure to sediment
      associated PAH. An apparent site-specific bioavailability limitation of sediment
      associated PAH was found for a site contaminated by creosote. At this site, no
      toxic samples were less than 3.9 TU. Finally, the predictability of the sigmaPAH
      model can be affected by species-specific responses (Hyalella vs Rhepoxynius);
      chemical specific (PAH vs DDT in H. azteca) biases, which are not incorporated in
      the equilibrium partitioning model; and the uncertainty from site-specific
      effects (creosote vs other sources of PAH contamination) on the bioavailability
      of sediment-associated PAH mixtures.

PMID- 11521843
TI  - Testing a multimedia compartmental model with monitoring data.
AB  - Based on its geographic similarity and nested structure, a chemical transport and
      transformation model developed in The Netherlands was adopted to a nine-parish,
      5,400-km2 area in southern Louisiana, USA, and tested for its ability to predict
      concentrations in the environment. SimpleBox 2.0 represents a class of models
      that compartmentalize the air, water, soil, sediment, and plants into boxes while
      maintaining a high degree of detail for processes within and between boxes. Past
      use has been in the evaluative mode, primarily where qualitative predictions of
      chemical behavior and distribution are made. Limited testing of model-predicted
      versus measured concentrations have been attempted. In recent years, quality and
      quantity of emission and monitoring data have improved dramatically. Such
      information was used in calibration and validation exercises with eight chemicals
      in the Louisiana chemical corridor, which receives inputs from urban, industrial,
      and agricultural sources. Geographically, the corridor was nested within the
      state of Louisiana, which was in turn nested within the continental United
      States. Parameter sensitivity studies, including transport coefficients,
      temperature, and degradation half-life revealed that the latter produces the
      largest range of variation in predicted concentrations. Published half-life data
      were used with benzene, vinyl chloride, 1,1,1-trichloethane, and atrazine in a
      calibration phase with 1995 monitoring data at steady state; this allowed
      selection of the appropriate emission database. A validation exercise was
      performed with toluene, styrene, trichloroethylene, and metribuzin. Predictions
      were compared to average measured concentrations. Atrazine and metribuzin reside
      primarily in the water; the others reside in the air. The predicted
      concentrations for benzene, metribuzin, and trichloroethylene were low by a
      factor of less than two. Vinylchloride, toluene, and 1,1,1-trichloroethane were
      low by factors between 3 and 10. Styrene and atrazine were low by factors of 45
      and 65, respectively.

PMID- 11521844
TI  - Comparison of different life-cycle impact assessment methods for aquatic
      ecotoxicity.
AB  - Human and ecotoxicity impact categories are problematic to quantify within life
      cycle impact assessment (LCIA) because their local scope makes them difficult to
      aggregate with the traditional global-impact categories used in life-cycle
      assessment (LCA). For being able to assess local impacts such as toxicity, LCIA
      developers increasingly include fate modeling into LCA. This article follows this
      development by comparing different LCIA methods for aquatic ecotoxicology and by
      investigating the importance of fate within LCIA, the necessity of considering
      freshwater and seawater compartments separately, and the key degradation and
      intermedia transfer processes involved. The methods are compared by assessing an
      example study of domestic clothes washing in former West Germany. Four LCIA
      methods are selected and applied to four substances emitted during the washing
      process. The conclusion is that the consideration of environmental fate does
      matter and that aquatic ecotoxic impacts can differ significantly for the same
      substance in freshwater and in marine ecosystems. The way (bio)degradation,
      photolysis, volatilization, and transfer from agricultural soils are considered
      plays an important role as do the system boundaries chosen. This means that the
      LCIA methodology should remain flexible so that appropriate methods can be chosen
      for different applications. Fate models being developed in the environmental risk
      assessment of chemicals can contribute to the further improvement of LCIA
      methods.

PMID- 11521845
TI  - Covariation in individuals' sensitivities to bitter compounds: evidence
      supporting multiple receptor/transduction mechanisms.
AB  - People vary widely in their sensitivities to bitter compounds, but the
      intercorrelation of these sensitivities is unknown. Our goal was to investigate
      correlations as a function of individual sensitivities to several bitter
      compounds representative of different chemical classes and, from these
      correlations, infer the number and variety of potential bitterness transduction
      systems for these compounds. Twenty-six subjects rated and ranked quinine HCl,
      caffeine, (-)-epicatechin, tetralone, L-phenylalanine, L-tryptophan, magnesium
      sulfate, urea, sucrose octaacetate (SOA), denatonium benzoate, and n
      propylthiouracil (PROP) for bitterness. By examining individual differences,
      ratings and rankings could be grouped into two general clusters-
      urea/phenylalanine/tryptophan/epicatechin, and quinine/caffeine/SOA/denatonium
      benzoate/tetralone/magnesium sulfate-none of which contained PROP. When subjects
      were grouped into the extremes of sensitivity to PROP, a significant difference
      was found in the bitterness ratings, but not in the rankings. Therefore, there
      are also subjects who possess diminished absolute sensitivity to bitter stimuli
      but do not differ from other subjects in their relative sensitivities to these
      compounds.

PMID- 11521846
TI  - Cross-modal attentional deficits in processing tactile stimulation.
AB  - In order to substantiate recent theorization on the possible links between the
      causes of the attentional blink and the psychological refractory period phenomena
      (e.g., Jolicoeur, 1999a), four experiments are reported in which two target
      stimuli, T1 and T2, were presented in different modalities at varying stimulus
      onset asynchronies (SOAs), with each stimulus being associated with a distinct
      task, Task1 and Task2. In Experiment 1, T1 was a tone, and Task1 was a speeded
      vocal response based on pitch. T2 was a brief press applied to either of two
      distal fingerpads, and Task2 was a speeded manual response based on tactile
      stimulus location. In Experiment 2, the same T1 as that used in Experiment 1 was
      presented, and in Task1 the subject either made a speeded vocal response based on
      pitch or ignored T1. T2 was a masked tactile stimulation, and Task2 was an
      unspeeded manual discrimination of the tactile stimulation location. This Task2
      was maintained in Experiments 3 and 4. The auditory T1 was replaced with a white
      digit embedded in a rapid serial visualization presentation of a stream of black
      letters, and in Task1 the subject either made an unspeeded decision based on T1
      identity or ignored T1. In all the experiments, the results showed an SOA-locked
      impairment in Task2. As SOA was decreased, reaction times in the speeded Task2 of
      Experiment 1 increased, and accuracy in the unspeeded Task2 of Experiments 2-4
      decreased. The SOA-locked impairment was almost eliminated when T1 could be
      ignored or was absent. The results are discussed in terms of central processing
      limitations as the cause of such effects.

PMID- 11521847
TI  - Stream segregation of narrow-band noise bursts.
AB  - Normally hearing adults heard rapid alternations of a pair of band-limited noise
      bursts that had flat spectra (in terms of equal-loudness weighting of components)
      and sharp band edges. The bursts differed in center frequency (CF), but were
      matched on overall intensity, on bandwidth (BW) on a log frequency scale, and
      (roughly) on pitch strength. Listeners judged the ease with which the sequence
      could be held together perceptually in a single auditory stream (vs. forming
      separate high and low streams). Involuntary segregation was examined as a
      function of the following measures of frequency separation of the alternating
      noise bands: (1) the closest band edges, (2) the most remote band edges, (3) the
      CFs of the bands on a logarithmic scale, and (4) the BWs. Segregation was best
      predicted from the separation of the two CFs on a log-frequency scale (very
      strong effect). Increasing the BWs of the two alternating bursts (the same size,
      in log frequency, for both bands) also led to greater segregation (very weak
      effect).

PMID- 11521848
TI  - Contextual influences on the internal structure of phonetic categories: a
      distinction between lexical status and speaking rate.
AB  - Previous research has shown that phonetic categories have a graded internal
      structure that is highly dependent on acoustic-phonetic contextual factors, such
      as speaking rate; these factors alter not only the location of phonetic category
      boundaries, but also the location of a category's best exemplars. The purpose of
      the present investigation, which focused on the voiceless category as specified
      by voice onset time (VOT), was to determine whether a higher order linguistic
      contextual factor, lexical status, which is known to alter the location of the
      voiced-voiceless phonetic category boundary, also alters the location of the best
      exemplars of the voiceless category. The results indicated that lexical status
      has a more limited and qualitatively different effect on the category's best
      exemplars than does the acoustic-phonetic factor of speaking rate. This
      dissociation is discussed in terms of a production-based account in which
      perceived best exemplars of a category track contextual variation in speech
      production.

PMID- 11521849
TI  - The use of sequential probabilities in the segmentation of speech.
AB  - The present investigation addresses the possible utility of sequential
      probabilities in the segmentation of spoken language. In a series of five word-
      spotting and two control lexical decision experiments, high- versus low
      probability consonant-vowel (Experiments 1, 2, 5, and 7) and vowel-consonant
      (Experiments 1, 3, 4, and 6) strings were presented either in the nonsense
      contexts of target words (Experiments 1-3) or within the target words themselves
      (Experiments 4-7). The results suggest that listeners, at least for sequences in
      the onset position, indeed use sequential probabilities as cues for segmentation.
      The probability of a sound sequence influenced segmentation more when the
      sequence occurred within the target words (Experiments 4-7 vs. Experiments 1-3).
      Furthermore, the effects were reliable only when the sequences occurred in the
      onset position (Experiments 1, 2, 5, and 7 vs. Experiments 1, 3, 4, and 6).

PMID- 11521850
TI  - Informational primacy of visual dimensions: specialized roles for luminance and
      chromaticity in figure-ground perception.
AB  - Three experiments were conducted to examine the distinct contributions of two
      visual dimensions to figure-ground segregation. In each experiment, pattern
      identification was assessed by asking observers to judge whether a near-threshold
      test pattern was the same or different in shape to a high-contrast comparison
      pattern. A test pattern could differ from its background along one dimension,
      either luminance (luminance tasks) or chromaticity (chromaticity tasks). In each
      task, performance in a baseline condition, in which the test pattern was intact,
      was compared with performance in each of several degradation conditions, in which
      either the contour or the surface of the figure was degraded, using either
      partial occlusion (Experiment 1) or ramping (Experiments 2 and 3) of figure
      ground differences. In each experiment, performance in luminance tasks was worst
      when the contour was degraded, whereas performance in chromaticity tasks was
      worst when the surface was degraded. This interaction was found even when spatial
      frequencies were fixed across test patterns by low-pass filtering. The results
      are consistent with a late (postfiltering) dual-mechanism system that processes
      luminance information to extract boundary representations and chromaticity
      information to extract surface representations.

PMID- 11521851
TI  - Differential activation solution to the motion correspondence problem.
AB  - The correspondence problem arises in motion perception when more than one motion
      path is possible for discontinuously presented visual elements. Ullman's (1979)
      "minimal mapping" solution to the correspondence problem, for which costs are
      assigned to competing motion paths on the basis of element affinities (e.g.,
      greater affinity for elements that are closer together), is distinguished from a
      solution based on the differential activation of directionally selective motion
      detectors. The differential activation account was supported by evidence that
      path length affects detector activation in a paradignm for which motion
      correspondence is not a factor. Effects on detector activation in this paradigm
      also were the basis for the successful prediction of path luminance effects on
      solutions to the motion correspondence problem. Finally, the differential
      activation account was distinguished from minimal mapping theory by an experiment
      showing that the perception of an element moving simultaneously in two directions
      does not depend on whether the two motions are matched in path-length determined
      affinity; it is sufficient that the activation of detectors responding to each of
      the two motion directions is above the threshold level required for the motions
      to be perceived. Implications of the differential activation solution are
      discussed for the stability of perceived motions once they are established, and
      the adaptation of perceived and unperceived motions.

PMID- 11521852
TI  - A Simon effect induced by induced moton and location: evidence for a direct
      linkage of  cognitive and motor maps.
AB  - It has been argued that two distinct maps of visual space are formed: a cognitive
      map that is susceptible to illusions, and a motor map that represents the
      physical world veridically. In the present study, subjects responded to a
      nonspatial attribute of a visual target stimulus by pressing a left or right key,
      while an illusory horizontal displacement of the target was induced. A Simon-type
      effect was obtained to the induced target motion or position shift-that is,
      responses were faster when the illusory target motion or location corresponded to
      the response position. Further experiments indicated that the observed effects
      cannot be accounted for by attentional shifts. These results suggest that the
      content of the cognitive map does not only influence perceptual judgments but is
      also responsible for the automatic activation of response codes. In other words,
      perception and action seem to be fed by a common, cognitively penetrable, spatial
      representation.

PMID- 11521853
TI  - Semantic codes are not used in integrating information across eye fixations in
      reading: evidence from fluent Spanish-English bilinguals.
AB  - The question of whether meaning can be extracted from unidentified parafoveal
      words was examined using fluent Spanish-English bilinguals. In Experiment 1,
      subjects fixated on a central cross, and a preview word was presented to the
      right of fixation in parafoveal vision. During the saccade to the parafoveal
      preview word, the preview was replaced by the target word, which the subject was
      required to name. In Experiment 2, subjects read sentences containing the target
      word, and, as in the naming task, a preview word was replaced by the target word
      when the subject's saccade crossed a boundary location. In both experiments,
      preview words were identical to the target word, translations, orthographic
      controls for the translations, or unrelated words in the opposite language. In
      both experiments, the preview benefit from the translation conditions was no
      greater than would be predicted by the orthographic similarity of the preview to
      the target. Hence, the data indicated that subjects obtained no useful semantic
      information from words seen parafoveally that enabled them to identify them more
      quickly on the subsequent fixation.

PMID- 11521854
TI  - Visual marking beside the mark: prioritizing selection by abrupt onsets.
AB  - In a standard visual marking experiment, observers are presented with a display
      containing one set of elements (old elements) followed after a certain time
      interval by a second set of elements (new elements). The task of observers is to
      search for a target among the new elements. Typically, the time to find the
      target depends only on the number of new elements in the display and not on the
      number of old elements, showing that observers search only among the new
      elements. This effect of prioritizing new elements over old elements is explained
      in terms of top-down inhibition of old objects-that is, visual marking (Watson &
      Humphreys, 1997). The present study addressed whether this prioritizing is in
      fact mediated by top-down inhibition of old objects, as suggested by Watson and
      Humphreys (1997), or whether it is mediated by the abrupt onsets of the newly
      presented elements (Yantis & Jonides, 1984). In three experiments, the
      presentations of the old and new elements were or were not accompanied by a
      luminance change. The results showed that if new elements were equiluminant with
      the background, no visual marking occurred, suggesting that new elements must
      have a luminance onset in order to be prioritized over old elements. Implications
      for current theories on visual selection are discussed.

PMID- 11521855
TI  - Visual search for dimensionally redundant pop-out targets: evidence for parallel
      coactive processing of dimensions.
AB  - In two visual search experiments, the detection of singleton feature targets
      redundantly defined on multiple dimensions was investigated. Targets differed
      from the distractors in orientation, color, or both (redundant targets). In
      Experiment 1, the various target types were presented either in separate blocks
      or in random order within blocks. Reaction times to redundant targets
      significantly violated the race model inequality (Miller, 1982), but only when
      there was constancy of the target-defining dimension(s) within trial blocks. In
      Experiment 2, there was dimensional variability within blocks. Consistent with
      Experiment 1, constancy of the target-defining dimension(s), but this time across
      successive trials (rather than within blocks), was critical for observing
      violations of the race model inequality. These results provide evidence for
      parallel-coactive processing of multiple dimensions, consistent with the
      dimension-weighting account of Muller, Heller, and Ziegler (1995).

PMID- 11521856
TI  - Driving attention with the top down: the relative contribution of target
      templates to the linear separability effect in the size dimension.
AB  - Bauer, Jolicoeur, and Cowan (1996a, 1996b, 1998) have shown that visual search
      for a target among distractors is apparently serial if the target is nonlinearly
      separable from the distractors in a particular feature space (e.g., color or
      size). In contrast, if the target is linearly separable from the distractors,
      search is relatively easy and seemingly spatially parallel. We examined the
      contribution of top-down knowledge of the target to the linear separability
      effect on search. Two visual search experiments were conducted using small,
      medium, or large circles as targets. In the first experiment, participants could
      use knowledge of the target to guide search, whereas, in the second, the target
      was unknown on each trial. Search for a medium (nonlinearly separable) target
      among small or large distractors benefited least from knowledge of the target as
      compared with search for a small or large target. Thus, the linear separability
      effect can be determined in part by use of top-down knowledge to facilitate the
      detection of targets at the ends of a continuum defining the stimuli.

PMID- 11521857
TI  - Alkyl modified anionic siloxanes as pseudostationary phases for electrokinetic
      chromatography. I. Synthesis and characterization.
AB  - Anionic water soluble siloxane polymers have been synthesized and characterized
      for electrokinetic chromatography. Siloxane polymers are of interest in
      electrokinetic chromatography because of the wide variety of chemistries that can
      be developed based on these backbones, including much of the stationary phase
      chemistry developed in the last 30 years. The siloxanes in this study have a
      sulfonate functional group. The siloxanes have different length alkyl chains (C8,
      C12, C18) attached to the backbone in differing densities. The methylene
      selectivity generally increases with increasing alkyl chain length and with
      increasing alkyl chain density. The electrophoretic mobility appears to pass
      through a maximum as more alkyl chain is added to the siloxane backbone. The
      efficiency also would seem to pass through a maximum as more alkyl chain is
      added. The chemical selectivities of the siloxane polymers are very different
      from sodium dodecyl sulfate but are similar to each other.

PMID- 11521858
TI  - Experimental demonstration of the possibility to perform shear-driven
      chromatographic separations in micro-channels.
AB  - The possibility to perform shear-driven chromatographic separations in micro
      channels is demonstrated, using a novel laser-jet printed microfluidic channel
      system. The obtained theoretical plate numbers are in fair agreement with the
      theoretical calculations. Theoretical extrapolations of the separation speeds and
      detection limits which can be achieved when further miniaturizing the current
      system are presented as well.

PMID- 11521859
TI  - Effect of pendant chain lengths and backbone functionalities on the chemical
      selectivity of sulfonated amphiphilic copolymers as pseudo-stationary phases in
      electrokinetic chromatography.
AB  - Amphiphilic copolymers of AMPS (2-acrylamido-2-methyl-1-propanesulfonic acid) and
      hydrophobic monomers with various chemical structures were synthesized,
      characterized and used as novel electrokinetic chromatography polymeric pseudo
      stationary phases, showing significant chemical selectivity differences from that
      of the conventional monomeric pseudo-stationary phase, sodium lauryl sulphate.
      Copolymers of AMPS and methacrylates with different pendant chain lengths (C8,
      C12 and C18) were investigated and no significant difference in chemical
      selectivity was observed among them. However, the spacer bonding chemistry was
      shown to contribute to significant chemical selectivity difference, e.g.
      poly(AMPS-lauryl methacrylate) showed different chemical selectivity from
      poly(AMPS-lauryl methacrylamide). Linear solvation energy relationship analysis
      of 20 solutes by eight different polymeric pseudo-stationary phases was employed
      to investigate the solute molecule structural contributions to the retention.
      Hydrogen-bonding properties (described by system constants b and a) of poly(AMPS
      alkyl methacrylamide) were found stronger than those of poly(AMPS-alkyl
      methacrylate).

PMID- 11521860
TI  - Microfabrication of polydimethylsiloxane electrospray ionization emitters.
AB  - Microfabricated polydimethylsiloxane (PDMS) emitters for electrospray ionization
      mass spectrometry (ESI-MS) were implemented as tips along the edge of the PDMS
      device by three methods which utilize soft lithography processes. These
      microfabrication methods for producing PDMS emitters as an integral part of a
      microfluidic device will facilitate development of more complex microfluidic
      analysis systems using ESI-MS.

PMID- 11521861
TI  - Extension of the application range of UV-absorbing organic solvents in capillary
      electrophoresis by the use of a contactless conductivity detector.
AB  - A contactless conductivity detection (CCD) system is used for capillary zone
      electrophoresis (CZE) with non-aqueous solvents of the buffering background
      electrolyte, which exhibit strong UV absorbance below 230 nm. It is found that
      the CCD characteristics with such solvents (propylene carbonate, N,N
      dimethylformamide and N.N-dimethylacetamide as examples) is the same as with
      aqueous solutions: the same signal and noise is obtained for a given electric
      conductance of the background electrolyte, independent of the kind of the
      solvent. Therefore CCD enables the extension of the application range to solvents
      with restricted use for common UV detection in CZE due to their unfavourable or
      even unfitting optical properties. The applicability of CCD is demonstrated by
      CZE of aliphatic ammonium compounds in these solvents.

PMID- 11521862
TI  - Sample stacking in laboratory-on-a-chip devices.
AB  - Sample stacking is a very important sample concentration technique. It has been
      used widely in capillary electrophoresis (CE). There are many different stacking
      techniques. One of the most popular techniques is called "field-amplified sample
      stacking" where an electric field discontinuity is set up across a concentration
      boundary. Charged analytes will then automatically stacked due to velocity
      changes after they cross the concentration boundary. There are several different
      strategies to perform sample stacking in microfluidic laboratory-on-a-chip
      devices. One could simply inject a plug of low concentration buffer containing
      sample into a channel surrounded by high concentration buffer. The electric field
      is then applied to stack the sample and move the whole plug into the separation
      channel. One could also stack the sample in a side channel adjacent to the
      separation channel. The disadvantage of this sample stacking technique is the
      difficulty in control of the precise location of stacked sample. We present a new
      sample stacking technique applied specifically to microfluidic laboratory-on-a
      chip devices. Up to hundreds of fold increases in sample concentration can be
      achieved. We have also combined this stacking with electrophoretic separation in
      the same device.

PMID- 11521863
TI  - Channel-specific coatings on microfabricated chips.
AB  - This paper reports channel-specific immobilization of fluorescein-5
      isothiocyanate (FITC)-labeled bovine serum albumin and beta-galactosidase on
      microchips with a central channel and two crossing channels; referred to as a
      double cross channel configuration. Solvent wells at the termini of all channels
      were used to store reagents. Coatings were applied in multiple steps using
      electroosmotically driven flow to deliver reagents to specific channels in the
      chip. The first step in all coating reactions was derivatization of the capillary
      walls with an organosilane having a reactive pendant functional group. As the
      silylating reagent was transported from the reagent storage well to a specific
      waste well, capillary walls in the route of transport were silylated. Flow was
      maintained throughout a reaction. The route of transport, and thus the
      specificity of channel coating, were controlled by the well to which negative
      potential was applied. Flow in a multichannel network takes the shortest route
      between the electrodes delivering the motive potential. The second reagent in the
      reaction was delivered from a different well and took a different path through
      the channel network, as did other reagents. Only the channel being coated was in
      the flow path of all the reagents used in the coating process. The zone of
      immobilization in the case of FITC-labeled albumin was determined with confocal
      fluorescence microscopy. Enzyme activity of immobilized beta-galactosidase (beta
      Gal) was monitored by following the hydrolysis of fluorescein mono-beta-D
      galactopyranoside to fluorescein with laser-induced fluorescence.

PMID- 11521864
TI  - Shah convolution differentiation Fourier transform for rear analysis in microchip
      capillary electrophoresis.
AB  - This paper first reports the application of Shah convolution differentiation
      Fourier transform for rear analysis. Rear analysis eliminates the need to create
      a well-defined and reproducible sample plug, thus making the operation simpler.
      The number of solution reservoirs, for microchip capillary electrophoresis (CE),
      could be reduced from the usual four to three. Sample bias in CE could be avoided
      too. The separation channel was first filled with the fluorescent sample
      solution, and subsequently flushed out with the buffer. The rear of each analyte
      zone gives rise to its flight of sigmoid-shaped steps in the time-domain. The
      time-domain detector signal was first differentiated and then Fourier transform
      was performed. The Fourier transform results were represented in the form of a
      magnitude plot. It is proposed that this would be as equally applicable to other
      separation techniques (e.g., chromatography) and detection methods (e.g.,
      absorption).

PMID- 11521865
TI  - Photopolymerized sol-gel frits for packed columns in capillary
      electrochromatography.
AB  - Porous sol-gel frits are fabricated in a capillary column by filling it with a
      solution of 3-(trimethoxysilyl)propyl methacrylate, hydrochloric acid, water,
      toluene (porogen), and a photoinitiator (Irgacure 1800) and exposing it to UV
      light at 365 nm for 5 min. The separation column (30 cm x 75 microm I.D.)
      contains between the inlet and outlet frits a 15-cm packed segment filled with 5
      microm silica particles modified with the chiral compound (S)-N-3,5
      dinitrobenzoyl-1-naphthylglycine. A detection window (1 mm long) is placed
      immediately after the outlet frit. To demonstrate the performance of this chiral
      separation column, mixtures of 16 different amino acids (three of which are not
      naturally occurring) derivatized with the fluorogenic reagent 4-fluoro-7-nitro
      2,1,3-benzoxadiazole were separated by capillary chromatography. The enantiomeric
      separation of the column results in a resolution ranging from 1.21 to 8.29, and a
      plate height ranging from 8.7 to 39 microm.

PMID- 11521866
TI  - Application of hydrophobic anion-exchange phases in capillary
      electrochromatography.
AB  - Capillary electrochromatography (CEC) requires stationary phases that enable
      appropriate electroosmotic propel under various conditions. Analyte retention can
      be controlled through hydrophobic or electrostatic interaction with the packing
      material. The development and characterization of new strong anion-exchange
      materials with additional hydrophobic moieties (SAX/C18 mixed-mode phases) is
      described. The synthesis was based on polymer encapsulation of porous silica. The
      phases were systematically characterized by means of elemental analyses, HPLC
      frontal analyses and CEC experiments. The studies focused on the influence of
      various parameters (e.g., pH, kind of buffer, capillary wall) on the
      electroosmotic flow (EOF). Phases with high anion-exchange capacity generated a
      fast and constant EOF over a wide pH range. Long-time stability of EOF and
      hydrophobic retention under CEC conditions were demonstrated within the course of
      100 consecutive injections. The applicability of the SAX/C18 phases in
      appropriate buffer systems is demonstrated for neutral, acidic and basic
      compounds.

PMID- 11521867
TI  - Electrochromatographic characterization of etched chemically-modified capillaries
      with small synthetic peptides.
AB  - In this investigation, various capillary electrochromatographic (CEC) experiments
      have been employed to characterize the properties of etched, chemically-modified
      surfaces of open tubular capillary columns with peptides as solute probes and
      under conditions of variable voltage, temperature and solvent composition. The
      separation performance of etched capillaries with either n-octadecyl or liquid
      crystal moieties derived from a cholesterol phase bonded to the surface were
      compared. With the liquid crystal bonded species, interesting and significantly
      different variations in retention behavior of peptides are obtained compared to
      those observed with the corresponding n-octadecyl modified surfaces by changes in
      temperature, solvent composition and field strength. These peptide separations
      illustrate the usefulness of this CEC approach for practical applications, where
      both the retention characteristics of the charged analytes as well as the
      selectivity differences due to the surface properties of the etched chemically
      modified surfaces of open tubular capillary columns can be rationally modulated.
      As in HPLC, appropriate choice of CEC experimental variables, including the
      chemical properties of the immobilized ligand(s), represents a powerful tool for
      optimizing resolution.

PMID- 11521868
TI  - Novel monolithic columns with templated porosity.
AB  - A new type of monolithic stationary phase was prepared within the confines of
      fused-silica tubing by in situ polymerization of divinylbenzene or ethylene
      dimethacrylate either with styrene or butyl methacrylate. The porosity of the
      monolith was dictated by silica beads packed in the capillary prior to flushing
      the column with the monomeric solution. Subsequent washing of the polymeric rod
      with sodium hydroxide rendered a porous monolith that was used for both micro-LC
      and capillary electrochromatography. The novelty of the approach presented herein
      lies in preparing the polymer within the confines of a fused-silica capillary.
      The challenges posed in this new context and their resolution are presented in
      detail. In addition, this study proposes that in addition to tailoring the pore
      size, the silica beads, through their surface chemistry, can influence the
      surface characteristics of the finished polymer monolith. For example, the data
      suggests that octadecyl modified silica particles interacted with hydrophobic
      moieties of monomers before initiation of polymerization, thus dictating their
      orientation in the resulting polymer.

PMID- 11521869
TI  - Ion chromatography on-chip.
AB  - On-chip separation of inorganic anions by ion-exchange chromatography was
      realized. Micro separation channels were fabricated on a silicon wafer and sealed
      with a Pyrex cover plate using standard photolithography, wet and dry chemical
      etching, and anodic bonding techniques. Quaternary ammonium latex particles were
      employed for the first time to coat the separation channels on-chip. Owing to the
      narrow depths of the channels on the chip, 0.5-10 microm, there were more
      interactions of the analytes with the stationary phase on the chip than in a 50
      microm I.D. capillary. With off-chip injection (20 nl) and UV detection, NO2-,
      NO3-, I-, and thiourea were separated using 1 mM KCl as the eluent. The linear
      ranges for NO2- and NO3- are from 5 to 1000 microM with the detection limits of
      0.5 microM.

PMID- 11521870
TI  - Determination of the molecular mass distribution of synthetic polymers by size
      exclusion electrochromatography.
AB  - The performance of size-exclusion electrochromatography (SEEC) for the mass
      distribution analysis of synthetic polymers was studied and compared to
      conventional, pressure-driven size-exclusion chromatography (SEC). Electroosmotic
      flow control, within-day, day-to-day and column-to-column repeatability were
      determined for SEEC with respect to retention and separation efficiency. It was
      shown that by using the retention ratio instead of the migration time, the
      precision of the mass distribution calculations is sufficiently high, and that
      similar distributions were obtained for a sample analyzed by pressure-driven SEC
      and by SEEC. Furthermore, hexafluoroisopropanol was demonstrated to be a new and
      potent solvent for SEEC. It was used for the separation of narrow
      polymethylmethacrylate standards and several commercially important polymers such
      as polycarbonate, polycaprolactam and poly(ethylene terephthalate), using UV
      detection in the deep UV region (195-230 nm).

PMID- 11521871
TI  - Capillary electrochromatographic enantioseparations using a packed capillary with
      a 3 microm OD-type chiral packing.
AB  - Enantiomer separations by capillary electrochromatography (CEC) using a packed
      capillary were investigated. As a chiral stationary phase, an OD-type packing
      material of 3 microm particle diameter, which is a silica-gel based material
      coated with cellulose tris(3,5-dimethylphenylcarbamate), was employed. The chiral
      packing was packed into a 100 microm I.D. fused-silica capillary by a pressurized
      method. Several racemic enantiomers were successfully resolved with acidic or
      basic buffers containing acetonitrile as mobile phases. The separation
      efficiencies obtained in this chiral CEC system were superior to those in the
      previously reported chiral CEC system using 5 microm particles. The typical plate
      heights obtained for several enantiomers were 4.6-6.6 microm or reduced plate
      heights of 1.5-2.2. Good repeatabilities in the migration time, peak height, and
      corrected peak area were observed as well as for the plate number. As an
      application study of this CEC system, an optical purity test was carried out by
      using benzoin enantiomers. A 1% content of one enantiomer in the other enantiomer
      was successfully separated and detected.

PMID- 11521872
TI  - On-chip definition of picolitre sample injection plugs for miniaturised liquid
      chromatography.
AB  - The fabrication of components for a miniaturised liquid chromatography system on
      silicon has recently been reported by our research group [J. Cap. Electrophoresis
      Microchip Technol. 6 (1999) 33; Analyst 125 (2000) 25]. To date, inlet and outlet
      connection ports, separation micro-channels (20-200 microm in width, 0.5-10
      microm in depth, 15-60 cm in length), and an intersection for picolitre injection
      have been etched on a silicon wafer and then sealed with a Pyrex cover plate on
      which platinum electrodes for on-chip detection have been patterned. The platinum
      electrodes have been used for the amperometric detection of phenol, using 20 nl
      off-chip injection. In this work we present our latest results obtained with on
      chip pressure driven picolitre injection, designed to realize the full
      capabilities of this micro-LC system. The injection volume is dependent on the
      micro-channel depth, width, and also on the intersection length, allowing
      injection in the low nanolitre to picolitre range.

PMID- 11521873
TI  - Microfabricated capillary array electrophoresis DNA analysis systems.
AB  - Microfabricated "laboratory-on-a-chip" systems are revolutionizing all aspects of
      genetic analysis. The development of capillary array electrophoresis (CAE)
      microchannel plate devices makes possible the performance of 96 or more high
      speed separations in parallel on a single wafer-scale device. The fluorescently
      labeled DNA samples are detected within the microchannels with a novel four-color
      rotary confocal fluorescence scanner. The capabilities of this system for
      genotyping are demonstrated through multiplex separations of short tandem repeat
      and hereditary haemochromatosis allele-specific amplicons. Furthermore, with
      newly developed folded channel designs that maintain high resolution, these CAE
      microplate systems are used to perform 96 high-quality DNA sequencing separations
      in parallel to approximately 500 bases per capillary in less than 30 min. These
      densely packed microfabricated device technologies will facilitate the even more
      rapid collection of vast amounts of genetic data in the future.

PMID- 11521874
TI  - Capillary-based fully integrated and automated system for nanoliter polymerase
      chain reaction analysis directly from cheek cells.
AB  - A miniaturized, integrated and automated system based on capillary fluidics has
      been developed for nanoliter DNA analysis directly from cheek cells. All steps
      for DNA analysis, including injecting aqueous reagents and DNA samples, mixing
      the solutions together, thermal cell lysis, polymerase chain reaction (PCR),
      transfer and injection of PCR product, separation, sizing and detection of those
      products are performed in a capillary-based integrated system. A small amount of
      cheek cells collected by a plastic toothpick is directly dissolved in the PCR
      cocktail in a plastic vial or mixed on-line with a small volume of PCR cocktail
      (125 nl) in the capillary. After thermal cell lysis and PCR in a microthermal
      cycler, the DNA fragments are mixed with DNA size standards and transferred to a
      micro-cross for injection and separation by capillary gel electrophoresis.
      Programmable syringe pumps, switching valves, multiposition and freeze-thaw
      valves are used for microfluidic control in the entire system. This work
      establishes the feasibility of performing all the steps of DNA analysis from real
      samples in a capillary-based nanoliter integrated system.

PMID- 11521875
TI  - Analysis of dopamine D4 receptor gene polymorphism using microchip
      electrophoresis.
AB  - A microfabricated electrophoresis device was used for rapid polymerase chain
      reaction product analysis in genotyping the dopamine D4 receptor gene (DRD4) 48
      base pairs repeat polymorphism. An allelic ladder, prepared from homozygous
      individuals, was used as internal standard during the microchip electrophoresis
      based analysis. Comparison of this novel separation method with the conventional
      slab gel and previously reported ultra-thin-layer techniques confirmed the
      reliability of this new method. Genotyping of 332 healthy Hungarian individuals
      gave the following allele frequencies: two-repeat: 0.089; three-repeat: 0.026;
      four-repeat: 0.674; five-repeat: 0.011; six-repeat: 0.002; seven-repeat: 0.189;
      eight-repeat: 0.011. The genotype frequencies obtained showed no deviation from
      the Hardy-Weinberg equilibrium (p>0.903), further underlying the reliability of
      this new genotyping technique.

PMID- 11521876
TI  - Peptide mapping by capillary zone electrophoresis: how close is theoretical
      simulation to experimental determination.
AB  - A multi-variable computer model is presented for the prediction of the
      electrophoretic mobilities of peptides at pH 2.5 from known physico-chemical
      constants of their amino acid residues. The model is empirical and does not claim
      any theoretical dependencies; however, the results suggest that, at least at this
      pH, peptides may be theoretically represented as classical polymers of freely
      joined amino acid residues of unequal sizes. The model assumes that the
      electrophoretic mobility can be represented by a product of three functions that
      return the contributions of peptide charge, length and width, respectively to the
      mobility. The model relies on accurate experimental determination of the
      electrophoretic mobilities of a diverse set of peptides, by capillary zone
      electrophoresis (CZE), at 22 degrees C, with a 50 mM phosphate buffer, at pH 2.5.
      The electrophoretic mobilities of a basis set of 102 peptides that varied in
      charge from 0.65 to 16 and in size from two to 42 amino acid residues were
      accurately measured at these fixed experimental conditions using a stable 10%
      linear polyacrylamide-coated column. Data from this basis set was used to derive
      the peptide charge, length, and width functions respectively. The main purpose of
      this endeavor is to use the model for the prediction of peptide mobilities at pH
      2.5, and for simulation of CZE peptide maps of protein digests. Excellent
      agreement was obtained between predicted and experimental electrophoretic
      mobilities for all categories of peptides, including the highly charged and the
      hydrophobic. To illustrate the utility of this model in protein studies it was
      used to simulate theoretical peptide maps of the digests of glucagon and horse
      cytochrome c. The resulting maps were compared and contrasted with their
      experimental counterparts. The potential of this approach and its limitations are
      discussed.

PMID- 11521877
TI  - Coupling continuous separation techniques to capillary electrophoresis.
AB  - One of the weak points of capillary electrophoresis is the need to implement
      rigorously sample pretreatment because its great impact on the quality of the
      qualitative and quantitative results provided. One of the approaches to solve
      this problem is through the symbiosis of automatic continuous flow systems (CFSs)
      and capillary electrophoresis (CE). In this review a systematic approach to CFS
      CE coupling is presented and discussed. The design of the corresponding interface
      depends on three factors, namely: (a) the characteristics of the CFS involved
      which can be non-chromatographic and chromatographic; (b) the type of CE
      equipment: laboratory-made or commercially available; and (c) the type of
      connection which can be in-line (on-capillary), on-line or mixed off/on-line.
      These are the basic criteria to qualify the hyphenation of CFS (solid-phase
      extraction, dialysis, gas diffusion, evaporation, direct leaching) with CE
      described so far and applied to determine a variety of analytes in many different
      types of samples. A critical discussion allows one to demonstrate that this
      symbiosis is an important topic in research and development, besides separation
      and detection, to consolidate CE as a routine analytical tool.

PMID- 11521878
TI  - Separation of antithrombin III variants by micellar electrokinetic
      chromatography.
AB  - The characterisation of proteins is still one of the most challenging analytical
      tasks in modern bioanalysis. Due to the complex structure of proteins, several
      analytical techniques are often required to get sufficient information.
      Antithrombin III (AT III), a high-molecular-mass plasma glycoprotein which is an
      important protease inhibitor and the main modulator of thrombin activity,
      circulates in plasma in two isoforms, the so-called AT III-alpha (90-95%) and 
      beta (5-10%). Micellar electrokinetic chromatography was used to analytically
      separate these AT III variants, which differ in their affinity to the
      polysaccharide heparin.

PMID- 11521879
TI  - Electrophoretic mobilities of cationic analytes in non-aqueous methanol,
      acetonitrile and their mixtures. Influence of ionic strength and ion-pair
      formation.
AB  - The mobilities of cationic analytes in organic solvents and water are compared,
      and the reasons for differences in the mobilities are discussed in detail. Actual
      mobilities (at background electrolyte concentration 10 mmol/l) of anilinium ions
      were determined by capillary zone electrophoresis in water, methanol,
      acetonitrile and mixtures of methanol and acetonitrile (in volume ratios 1:1, 1:3
      and 3:1). The actual mobilities correlated with the viscosity of the organic
      solvent: the products of actual mobility and viscosity were constant within 7%.
      However, these products were significantly larger in water. Larger products of
      mobility and viscosity in water were also found for unsubstituted anilinium when
      the absolute mobility (at zero ionic strength) was taken into consideration.
      Thus, ion-solvent interactions must be responsible for the seemingly high
      mobility in water compared with that in organic solvents. This finding can be
      explained by the effect of the ion on the water structure. Based on equilibrium
      constant for ion-pair formation given in the literature, about 20% of the main
      background electrolyte constituent (tetrapropylammonium perchlorate) is
      associated at 10 mmol/l concentration in acetonitrile. Comparison of the plot of
      the measured mobilities of the analytes vs. the square root of the corrected
      ionic strength of the background electrolyte in acetonitrile with the prediction
      based on the Debye-Huckel-Onsager theory showed the measured mobilities deviate
      negatively from the theoretical line. This is apparently due to ion pairing,
      which takes place for the analytes as well.

PMID- 11521880
TI  - On-line coupling of micro-enzyme reactor with micro-membrane chromatography for
      protein digestion, peptide separation, and protein identification using
      electrospray ionization mass spectrometry.
AB  - To miniaturize high-performance membrane chromatography, a poly(vinylidene
      fluoride) membrane medium, employed as the stationary phase, is sandwiched
      between two poly(dimethylsiloxane) substrates containing the microchannels. The
      microchannels are fabricated by the capillary molding technique, involving the
      use of capillaries as the channel template and the fluid inlet/outlet. The
      micro(micro)-membrane chromatography system is coupled with a micro-enzyme
      reactor containing immobilized trypsins for performing rapid protein digestion,
      peptide separation, and protein identification using electrospray ionization mass
      spectrometry. Separation performance of cytochrome c digest in micro-membrane
      chromatography is compared with the results obtained from a regular reversed
      phase micro-liquid chromatography. The efficacy and the potentials of micro
      membrane chromatography in tryptic mapping are reported. On-line integration of
      the micro-enzyme reactor with micro-chromatographic separation techniques and
      electrospray ionization mass spectrometry clearly provides a microanalytical
      platform for automated sample handling, minimized sample loss, and reduced sample
      consumption. It also provides enhanced detection sensitivity and dynamic range
      for the analysis of complex protein mixtures such as cell lysates in proteomics
      research.

PMID- 11521881
TI  - Capillary electrochromatography-laser-induced fluorescence method for separation
      and detection of dansylated dialkylamine tags in encoded combinatorial libraries.
AB  - LC-fluorescence and LC-MS methods have been previously reported for use in
      decoding bead-based combinatorial libraries. We present the use of capillary
      electrochromatography (CEC) for highly selective decoding in combination with
      laser-induced fluorescence (LIF) detection for high sensitivity. The results are
      compared to prior data obtained using HPLC with fluorescence detection. The use
      of CEC shows promise for miniaturization and multiplexing for future
      applications, and the use of LIF detection can allow for detection at sub-pmol
      amounts.

PMID- 11521882
TI  - Effect of various modes of pressurization on the separation in capillary
      electrochromatography.
AB  - In capillary electrophoresis and capillary electrochromatography, the driving
      factor of the separation is electroosmotic flow (EOF). Pressurized capillary
      electrochromatography, in which the separation is controlled by EOF as well as
      the pressure, becomes more and more attractive. We studied the influence of
      various pressures on capillary electrochromatographic separation. The results
      reveal that in pressurized capillary electrochromatography, which was performed
      by EOF combined with the forward and reverse pressure, the main driving factor is
      still the EOF. It was also found that, when reverse pressure was applied in
      capillary electrochromatography, the repeatability of the capillary
      electrochromatographic separation was increased dramatically.

PMID- 11521883
TI  - Competitive immunoassay for recombinant hirudin using capillary electrophoresis
      with laser-induced fluorescence detection.
AB  - A competitive immunoassay based on capillary electrophoresis (CE) with laser
      induced fluorescence (LIF) has been developed for the determination of
      recombinant hirudin (r-hirudin) in biological mixtures. Hirudin, a thrombin
      inhibitor, is a polypeptide of 65 amino acids. To check purity levels and perform
      pharmacokinetic studies of (r-hirudin), specific and reproducible analysis
      methods are demanded. The work involved the development of separation conditions
      allowing for routine analysis of plasma samples. In this study, r-hirudin was
      labeled with fluorescein isothiocyanate (FITC), and FITC-labeled r-hirudin was
      purified using high-performance liquid chromatography. The purified product was
      then mixed with the sample followed with the addition of anti-hirudin antibody.
      Free, antibody-bound, and tagged r-hirudin could be separated within 5 min by CE
      analysis using uncoated fused-silica capillary with high reproducibility. The
      developed method can be used to determine r-hirudin with good precision and a
      detection limit lower than 20 nM. This result demonstrates the feasibility of the
      CE-LIF immunoassay method for the determination of r-hirudin in plasma samples.

PMID- 11521884
TI  - Proteomics based on selecting and quantifying cysteine containing peptides by
      covalent chromatography.
AB  - This paper describes a procedure in which cysteine containing peptides from
      tryptic digests of complex protein mixtures were selected by covalent
      chromatography based on thiol-disulfide exchange. identified by mass
      spectrometry, and quantified by differential isotope labeling. Following
      disruption of disulfide bridges with 2,2'-dipyridyl disulfide, all proteins were
      digested with trypsin and acylated with succinic anhydride. Cysteine containing
      peptides were then selected from the acylated digest by disulfide interchange
      with sulfhydryl groups on a thiopropyl Sepharose gel. Captured cysteine
      containing peptides were released from the gel with 25 mM dithiothreitol (pH 7.5)
      containing 1 mM (ethylenedinitrilo)tetraacetic acid disodium salt and alkylated
      with iodoacetic acid subsequent to fractionation by reversed-phase liquid
      chromatography (RPLC). Fractions collected from the RPLC column were analyzed by
      matrix-assisted laser desorption ionization mass spectrometry. Based on isotope
      ratios of peptides from experimental and control samples labeled with succinic
      and deuterated succinic anhydride, respectively, it was possible to determine the
      relative concentration of each peptide species between the two samples. Peptides
      obtained from proteins that were up-regulated in the experimental sample were
      easily identified by an increase of the relative amount of the deuterated
      peptide. The results of these studies indicate that by selecting cysteine
      containing peptides, the complexity of protein digest could be reduced and
      database searches greatly simplified. When coupled with the isotope labeling
      strategy for quantification it was possible to determine proteins that were up
      regulated in plasmid bearing Escherichia coli when expression of plasmid proteins
      was induced. Up-regulation of several proteins of E. coli origin was also noted.

PMID- 11521885
TI  - Automated signature peptide approach for proteomics.
AB  - This paper addresses the issue of automating the multidimensional
      chromatographic, signature peptide approach to proteomics. Peptides were
      automatically reduced and alkylated in the autosampler of the instrument. Trypsin
      digestion of all proteins in the sample was then executed on an immobilized
      enzyme column and the digest directly transferred to an affinity chromatography
      column. Although a wide variety of affinity columns may be used, the specific
      column used in this case was a Ga(III) loaded immobilized metal affinity
      chromatography (IMAC) column. Ga(III)-IMAC is known to select phosphorylated
      peptides. Phosphorylated peptides selected by the affinity column from tryptic
      digests of milk were automatically transferred to a reversed-phase liquid
      chromatography (RPLC) column. Further fractionation of tryptic peptides on the
      RPLC column was achieved with linear solvent gradient elution. Effluent from the
      RPLC column was electrosprayed into a time-of-flight mass spectrometer. The
      entire process was controlled by software in the liquid chromatograph. With
      slight modification, it is possible to add multiple columns in parallel at any of
      the single column positions to further increase throughput. Total analysis time
      in the tandem column mode of operation was under 2 h.

PMID- 11521886
TI  - Characterization of the interaction between phospholipid and protein by capillary
      electrophoresis with laser-induced fluorescence detection.
AB  - We report an electrophoretic mobility shift-based method to study the
      interactions between phospholipids and proteins by capillary electrophoresis with
      laser-induced fluorescence detection. A fluorogenic dye, 3-(2-furoyl)quinoline-2
      carboxaldehyde (FQ), was used to label phosphatidylserine (PS). Then the FQ
      labeled PS (FQ-PS) was used as the fluorescent probe for monitoring the
      association between PS and bovine serum albumin (BSA). Two conjugates were
      observed to form between each PS species and BSA, indicating that two
      interactions exist between these PS species and BSA. We can also detect the
      competitive association with BSA between labeled PS and unlabeled PS. This method
      only needs a minute volume of sample. It is highly sensitive and can be used to
      detect the interaction between phospholipids and nanomolar concentrations of
      proteins, such as BSA.

PMID- 11521887
TI  - Detection of DNA adducts of benzo[a]pyrene using immunoelectrophoresis with laser
      induced fluorescence. Analysis of A549 cells.
AB  - Detection of benzo[a]pyrene diol epoxide (BPDE)-damaged DNA in a human lung
      carcinoma cell line (A549) has been performed using free zone affinity capillary
      electrophoresis with laser-induced fluorescence (LIF). Using BPDE as a model
      carcinogenic compound, the speed, sensitivity and specificity of this technique
      was demonstrated. Under free zone conditions, an antibody bound adduct was
      baseline-resolved from an unbound adduct in less than 2 min. The efficiencies of
      separation were in excess of 6 x 10(5) and 1 x 10(6) plates per meter for the
      antibody-bound and unbound adducts, respectively. Separation using a low ionic
      strength buffer permitted the use of a high electric field (830 V/cm) without the
      loss of resolving power. Using LIF detection, a concentration detection limit of
      roughly 3 x 10(-10) M was achieved for a 90-mer oligonuleotide containing a
      single BDPE. The use of formamide in the incubation buffer to enhance denaturing
      of DNA did not affect the stability of the complex between the antibody and the
      adducts. Using a fluorescently labeled BPDE-modified DNA adduct probe, a
      competitive assay was established to determine the levels of BPDE-DNA adducts in
      A549 cells.

PMID- 11521888
TI  - Analysis of post-harvest fungicides by micellar electrokinetic chromatography.
AB  - A method based on solid-phase extraction (SPE) and micellar electrokinetic
      chromatography (MEKC) was developed for the simultaneous determination of
      carbendazim, imazalil, methylthiophanate, O-phenylphenol, prochloraz,
      procimidone, thiabendazole and triadimefon residues in grape, lettuce, orange and
      tomato. Selectivity and resolution were studied changing the pH and the
      concentration of the buffer, the type and concentration of surfactant and the
      methanol content in the mobile phase. A buffer consisting of 4 mM borate with 75
      mM sodium cholate (pH 9.2) gave the best results. The recoveries of the
      fungicides in spiked fruit and vegetable samples ranged from 30 to 105%, and the
      limits of detection were between 0.1 and 1 mg kg(-1). The reproducibility and
      repeatability of the combination of SPE pretreatment and MEKC were good for all
      the compounds, except for imazalil and O-phenylphenol in oranges, due to some
      matrix compounds interfering with the separation. The method was applied to post
      harvest treated samples, and the fungicides were sometimes detected at
      concentration levels lower than maximum residue limits (MRLs).

PMID- 11521890
TI  - Liquid-liquid-liquid microextraction of nitrophenols with a hollow fiber membrane
      prior to capillary liquid chromatography.
AB  - A simple liquid-liquid-liquid microextraction device utilizing a 2 cm x 0.6 mm
      I.D. hollow fiber membrane was used to preconcentrate nitrophenols from water
      sample prior to capillary liquid chromatography (cLC) analysis. The extraction
      procedure was induced by the pH difference inside and outside the hollow fiber.
      The donor phase outside the hollow fiber was adjusted to pH approximately 1 with
      HCl; the acceptor phase was NaOH solution used at various concentrations. Organic
      solvent was immobilized into the pores of the hollow fiber. With stirring, the
      neutral nitrophenols outside the fiber were extracted into the organic solvent,
      then back extracted into 2 microl of basic acceptor solution inside the fiber.
      The acceptor phase was then withdrawn into a microsyringe and injected into the
      cLC system directly. This technique used a low-cost disposable extraction
      "device" and is very convenient to operate. Up to 380-fold enrichment of analytes
      could be achieved. This procedure could also serve as a sample clean-up step
      because large molecules and basic compounds were not extracted into the acceptor
      phase. The RSD (n=6) was less than 6.2%, while the linear calibration range was
      from 1 to 200 microg/ml with r>0.998. The procedure was applied to the analysis
      of seawater.

PMID- 11521891
TI  - Ionization of dichlorophenols for their analysis by capillary electrophoresis
      mass spectrometry.
AB  - In order to develop an advanced analytical method using capillary electrophoresis
      (CE) for non-volatile environmental pollutants such as endocrine disruptors,
      combination with mass spectrometry (MS) is necessary for their identification. We
      chose dichlorophenols (DCPs) as test samples because one of their isomers, 2,4
      DCP, is suspected to have endocrine disrupting effects. A preliminary study on
      their separation by CE-MS was performed using a laboratory-made electrospray
      ionization (ESI) interface. For the effective ionization of 2,4-DCP at the

PMID- 11521889
TI  - Optimizing separation conditions for polycyclic aromatic hydrocarbons in micellar
      electrokinetic chromatography.
AB  - We report the separation of polycyclic aromatic hydrocarbons (PAHs) using 0.1%
      poly(ethylene oxide) (PEO) in micellar electrokinetic chromatography (MEKC). In
      the presence of PEO, adsorption of PAHs on the capillary wall was reduced,
      leading to better resolution and reproducibility. Effects of tetrapentylammonium
      iodide (TPAI), dextran sulfate (DS), methanol, and sodium lauryl sulfate (SDS) on
      the separation of PAHs were elucidated. In terms of resolution and speed, DS,
      compared to TPAI, is a better additive for separation of PAHs. When using 0.1%
      PEO solution containing 45% methanol, 50 mM SDS, and 0.02% DS, separation of 10
      PAHs containing 2 to 5 benzene rings was accomplished in less than 12 min at 15
      kV in a commercial CE system. The method has also been tested for separating
      seven PAHs with high quantum yields when excited at 325 nm using a He-Cd laser.
      Unfortunately, separation of the seven PAHs was not achieved and sensitivity
      diminished under the same conditions. To optimize sensitivity, resolution and
      speed, a stepwise technique in MEKC has been proposed. The seven PAHs were
      resolved in 35 min at 15 kV when separation was performed in 0.1% PEO solution
      containing 35 mM SDS, 40% methanol and 0.02% DS for 2 min, and subsequently in
      0.1% PEO solution containing 20 mM SDS, 50% methanol, and 0.02% DS.

PMID- 11521892
TI  - Profiling of impurities in heroin by capillary electrochromatography and laser
      induced fluorescence detection.
AB  - Capillary electrochromatography (CEC) with laser-induced fluorescence (LIF)
      detection was investigated for the analysis of acidic and neutral impurities in
      heroin. The phenanthrene-like heroin impurities exhibit high native fluorescence
      when excited with a doubled argon ion laser (operating at 257 nm). The limit of
      detection for acetylthebaol is 66 pg ml(-1). CEC-LIF analysis of heroin samples
      of different geographical origin gave distinguishable peak-enriched
      chromatograms. A sulfonic acid C12 polymer monolith column provided similar
      resolving power to a 1.5 mm non-porous ODS column for the isocratic analysis of a
      refined heroin sample. Analysis of a crude heroin sample via a multi-step
      gradient CEC resolved a significantly higher number of peaks than gradient high
      performance liquid chromatography or micellar electrokinetic capillary
      chromatography.

PMID- 11521893
TI  - Therapeutic drug monitoring of antiepileptics by capillary electrophoresis.
      Characterization of assays via analysis of quality control sera containing 14
      analytes.
AB  - Quality assurance is an important aspect in therapeutic drug monitoring (TDM).
      Capillary electrophoresis (CE) assays for determination of (i) ethosuximide via
      direct injection of serum or plasma, (ii) lamotrigine after protein precipitation
      by acetonitrile and analysis of an aliquot of the acidified supernatant, and
      (iii) carbamazepine and carbamazepine-10,11-epoxide after solute extraction
      followed by analysis of the reconstituted extract are characterized via analysis
      of a large number of commercial quality control sera containing up to 14 analytes
      (9 of them are anticonvulsants) in sub-therapeutic, therapeutic and toxicologic
      concentration levels. CE data obtained in single determinations are shown to
      compare well with the spike values and the mean of data determined in other
      laboratories using immunoassays and/or high-performance liquid chromatography,
      values that are reported by the external quality control scheme. Carbamazepine
      and ethosuximide drug levels are also shown to agree well with those determined
      in our departmental drug assay laboratory using automated immunoassays. The
      presented data reveal the effectiveness of assay assessment via analysis of
      quality control sera and confirm the robustness of the assays for TDM in a
      routine setting.

PMID- 11521894
TI  - Capillary electrophoretic separation of uncharged polymers using polyelectrolyte
      engines. Theoretical model.
AB  - We recently demonstrated that the molecular mass distribution of an uncharged
      polymer sample can be analyzed using free-solution capillary electrophoresis of
      DNA-polymer conjugates. In these conjugates, the DNA is providing the
      electromotive force while the uncharged polydisperse polymer chains of the sample
      retard the DNA engine with different amounts of hydrodynamic drag. Here we
      present a theoretical model of this new analytical method. We show that for the
      most favourable, diffusion-limited electrophoresis conditions, there is actually
      an optimal DNA size to achieve the separation of a given polymer sample.
      Moreover, we demonstrate that the effective friction coefficient of the polymer
      chains is related to the stiffness of the two polymers of the conjugate, thus
      offering a method to estimate the persistence length of the uncharged polymer
      through mobility measurements. Finally, we compare some of our predictions with
      available experimental results.

PMID- 11521895
TI  - Simultaneous determination of hydrochlorothiazide and several inhibitors of
      angiotensin-converting enzyme by capillary electrophoresis.
AB  - A capillary electrophoresis method was developed for the simultaneous
      determination of hydrochlorothiazide and several angiotensin-converting enzyme
      (ACE) inhibitors: enalapril, lisinopril, quinapril, fosinopril, ramipril, and
      cilazapril. The most critical parameter is the pH of the running buffer.
      Separation was performed on a fused-silica capillary (52 cm total length x 75
      microm I.D.) using a sodium phosphate buffer (pH 7.25; 100 mM). The method was
      successfully applied to the quantitative determination of these compounds in
      their corresponding pharmaceutical formulation. The method was validated in terms
      of linearity of response, reproducibility and accuracy.

PMID- 11521896
TI  - Development and validation of a simple capillary zone electrophoresis method for
      the analysis of kanamycin sulfate with UV detection after pre-capillary
      derivatization.
AB  - Capillary zone electrophoresis was successfully applied to separate eight related
      substances of kanamycin and several minor unknowns from the main component.
      Strategies to enhance derivatization and selectivity and to optimize separation
      parameters involved the application of experimental designs. This chemometrical
      approach considers main effects as well as interactions of the influential
      parameters, thus conducting a more thorough investigation of the method than the
      common step-by-step approach. Central composite face centered designs established
      optimal separation conditions: 30 mM borax buffer, pH 10.0 containing 16.0% (v/v)
      methanol and optimal composition of derivatization reagent: 27 mg/ml 1,2-phthalic
      dicarboxaldehyde and 25 microl/ml mercaptoacetic acid in borate buffer, pH 10.4.
      The standard curves were linear over the concentration range of 0.007-1.01 mg/ml
      for the main component and 0.003-0.1 mg/ml for the related substances. The limit
      of quantitation was 0.14% (m/m) for the related substances and impurities (S/N=
      10). The assay method was used to determine the composition of several commercial
      samples. Quantitative analysis indicates potential usefulness of capillary
      electrophoresis as an alternative to the assay method prescribed in the European
      Pharmacopoeia and the United States Pharmacopeia.

PMID- 11521898
TI  - Selective and quantitative analysis of 4-hydroxybenzoate preservatives by
      microemulsion electrokinetic chromatography.
AB  - A microemulsion electrokinetic chromatography (MEEKC) method has been developed
      and validated for the determination of 4-hydroxybenzoates and their impurities.
      These materials are commonly known as parabens and are widely used as
      preservatives in foods, cosmetics and pharmaceuticals. The method was shown to be
      selective and quantitative for the methyl, ethyl, propyl and butyl esters of 4
      hydroxybenzoic acid. An internal standard, 4-hydroxyacetophenone, was employed to
      improve injection precision and detector linearity. In addition, 4-hydroxybenzoic
      acid, the major degradent, could also be monitored at the 0.1% (m/m) level. The
      method was successfully validated for assay and detection of the impurities in 4
      hydroxybenzoic acid methyl ester and 4-hydroxybenzoic acid propyl ester samples
      and for the determination of 4-hydroxybenzoic acid methyl ester in a liquid
      pharmaceutical formulation. The determination of paraben content by MEEKC in a
      liquid sample was consistent with HPLC analysis. This work is the first reported
      validated MEEKC method and shows that the methodology can be successfully
      implemented into routine quality control testing.

PMID- 11521897
TI  - Enantiomeric separation of R,S-naproxen by conventional and nano-liquid
      chromatography with methyl-beta-cyclodextrin as a mobile phase additive.
AB  - Chiral separations of R,S-naproxen mixtures were obtained on an achiral column
      (ODS) with methyl-beta-cyclodextrin as a mobile phase additive using conventional
      and nano-LC. The optimised mobile phase composition was 20 mmol l(-1) methyl-beta
      cyclodextrin, 20% (v/v) acetonitrile, and 50 mmol l(-1) sodium acetate buffer at
      pH 3 using hydrochloric acid for pH adjustment. In addition to UV detection at
      232 nm, amperometric detection was also investigated. Without using any internal
      standard, the reproducibility of amperometric detection (+1.05 V vs. Ag/AgCl)
      over a long analysis cycle in LC was greatly improved by choosing the peak area
      ratio between R- and S-naproxen as the analytical readout (the relative standard
      deviation was 2.11%) and enantiomeric purity could be assessed directly. This
      method was successfully employed for enantiomeric purity assessment in commercial
      naproxen tablets. Finally, successful transfer from conventional LC to nano-LC
      was realised, resulting in over 1000-fold reduction in reagent consumption.

PMID- 11521899
TI  - Analysis of 2beta-carbomethoxy-3beta-(4-fluorophenyl)-N-(3-iodo-E
      allyl)nortropane in rat plasma. II. Pharmacokinetic profile in male and female
      Sprague-Dawley rats evaluated by capillary electrophoresis.
AB  - This paper describes a pharmacokinetic study performed in Sprague-Dawley rats
      after i.v. administration of a single 6-mg/kg dose of 2beta-carbomethoxy-3beta-(4
      fluorophenyl)-N-(3-iodo-E-allyl)nortropane (Altropane). Plasma samples were
      collected from the retro-orbital sinus at times up to 3 h after drug
      administration, extracted by solid-phase extraction, and the drug levels
      determined by capillary electrophoresis (CE). Pharmacokinetic parameters were
      determined by a standard noncompartmental model using WinNonlin version 1.5. The
      maximum plasma concentrations, clearances of the drug, and areas under the curve
      for male and female rats were 5.74 and 7.26 microg/ml, 135.7 and 98.5 ml/kg x
      min, and 44.23 and 60.92 microg x min/ml, respectively. The drug was cleared very
      rapidly from the systemic circulation, with a terminal t(1/2) of 7 to 10 min and
      a mean residence time of about 11 min for both sexes. The volume of distribution
      was approximately 1 l/kg. No metabolites were detected when the samples were
      analyzed individually. However, after samples were pooled and concentrated,
      traces of two unknown peaks that may represent metabolites were detected in
      concentrates from the last two timepoints. Part I of this work [J. Chromatogr. A,
      895 (2000) 87] describes validation of CE methods for the analysis of aqueous and
      plasma samples of Altropane, including its solid-phase extraction from rat
      plasma.

PMID- 11521900
TI  - Determination of apparent binding constants of drugs by capillary electrophoresis
      using beta-cyclodextrin as ligand and three different linear plotting methods.
AB  - Capillary electrophoretic estimation of apparent binding constants (Kapp) for
      naproxen, salbutamol, indomethacine and procaine with beta-cyclodextrin is
      presented. While with naproxen and indomethacine this approach was
      straightforward and gave well compatible results by three different linearization
      plots (double reciprocal, x reciprocal and y reciprocal), with salbutamol a
      higher value than reported for the electromigration estimation of this magnitude
      was obtained (a fourfold increase). This difference is ascribed to the fact that
      the measurements were done in the acid region (while the reported values were
      obtained at higher pH values). As a matter of fact the values of Kapp, reported
      in this communication for salbutamol comply better with the value of Kapp (69.3)
      obtained by the solubility method.

PMID- 11521901
TI  - Potassium concentration differences in the vitreous humour from the two eyes
      revisited by microanalysis with capillary electrophoresis.
AB  - This paper presents a study of the variability of potassium concentrations in the
      vitreous humour of the two eyes of the same body at identical postmortem
      interval. The study was carried out by collecting microsample amounts (50 microl)
      of vitreous humour and by using an original method of capillary electrophoresis
      with indirect detection. The electrophoretic separations were carried out in a pH
      4.5 running buffer composed of 5 mmol/l imidazole, 5 mmol/l 18-crown-6 ether and
      6 mmol/l alpha-hydroxybutyric acid. Detection was by indirect UVabsorption at 214
      nm. Vitreous humour samples were collected from 57 medico-legal autopsies or
      external examinations of cases of sudden natural or violent deaths. All samples
      prior to analysis were diluted 1:20 with a 40 microg/ml aqueous solution of
      barium, the used internal standard, and finally injected by nitrogen pressure.
      The mean concentrations of potassium measured in the two eyes of all the cases
      included in the present study ranged from 4.1 to 23.5 mmol/l with the postmortem
      interval values varying from 7 to 144 h. A highly significant (P<0.0001) linear
      correlation was found between these two parameters as described by the equation:
      y=0.1698x+2.3587, r=0.89. The intra-eye variability of potassium concentrations
      was low with an average RSD of 3.89% (+/- 1.83 SD) (48 eyes, five samples per
      eye). No statistically significant difference was found between the potassium
      concentrations in the two eyes of the same subject in a group of 24 cases,
      excepting a single case.

PMID- 11521902
TI  - Use of beta-cyclodextrin in the capillary zone electrophoretic separation of the
      components of clandestine heroin preparations.
AB  - The present paper describes the methodological optimization and validation of a
      capillary zone electrophoresis method for the rapid determination of heroin,
      secondary products and additives present in clandestine heroin samples, by using
      20 mM beta-cyclodextrins in phosphate buffer, pH 3.23. Applied potential was 15
      kV and separation temperature was 24 degrees C; detection was by UV absorption at
      200 nm wavelength. Heroin samples were first dissolved in CHCl3-MeOH (96:4, v/v)
      and injected by pressure (0.5 p.s.i., 3 s; 1 p.s.i.=6894.76 Pa) after evaporation
      of the organic mixture and reconstitution in aqueous buffer. Under the described
      conditions, phenylethylamine (internal standard), morphine, monoacetylmorphine,
      heroin, acetylcodeine, papaverine, codeine and narcotine were baseline resolved
      in less than 10 min. The limit of detection was better than 1 microg/ml for each
      analyte. The study of the intra-day and day-to-day precision showed, in terms of
      migration times, RSDs < or = 0.71% and, in terms of peak areas, RSDs < or = 3.2%.
      Also, the evaluation of linearity and analytical accuracy of the method provided
      good results for all the analytes investigated, thus allowing its application to
      real cases of seized controlled drug preparations.

PMID- 11521903
TI  - Head-column field-amplified sample stacking in presence of siphoning. Application
      to capillary electrophoresis-electrospray ionization mass spectrometry of opioids
      in urine.
AB  - Capillary electrophoresis (CE) with head-column field-amplified sample stacking
      (FASS) in presence of a water plug inserted at the capillary tip is a robust
      approach providing a more than 1000-fold sensitivity enhancement when applied to
      low-conductivity samples that are analyzed in an integrated instrument. Employing
      modular systems comprising a small hydrodynamic buffer flow (siphoning) towards
      the capillary end and featuring UV absorption or electrospray ionization mass
      spectrometric (MS) detection, insertion of a water plug is demonstrated to
      deteriorate the performance of head-column FASS or making it unfunctional.
      Electroinjection in the absence of the water plug can be employed instead and is
      shown to provide a ng/ml sensitivity when applied to low conductivity samples.
      With some suction of sample into the capillary during electroinjection,
      contamination of the sample vial with buffer is thereby largely avoided.
      Electroinjection applied to the CE-ion trap MS-MS and MS-MS-MS analysis of
      twofold diluted urines, urinary solid-phase extracts and urinary liquid-liquid
      extracts is shown to provide much improved sensitivity compared to hydrodynamic
      injection of these samples. With electroinjection from diluted urine and urinary
      solid-phase extracts, the presence of free opioids and their glucuronic acid
      conjugates can be unambiguously confirmed in urines that were collected after
      single-dose administration of small amounts of opioids (tested with about 7 mg
      codeine and 25 mg dihydrocodeine, respectively). Thus, CE-multiple MS with direct
      electroinjection of opioids from untreated urines could prove to become a rapid
      and simple approach for unambiguous urinary testing of drug abuse. Procedures
      leading to the reduction of siphoning in modular CE setups are briefly discussed
      as well.

PMID- 11521904
TI  - Decrease in concentration of free catechins in tea over time determined by
      micellar electrokinetic chromatography.
AB  - Cancer chemoprevention is a new and important medical science and much interest
      has been focused on catechins, not only for their antioxidant activity, but also
      because of their known antimutagenic and antitumorigenic properties. Green tea
      and black tea, which are among the most popular beverages consumed worldwide,
      contain many different catechins. Due to the instability of catechins in
      solutions with neutral or basic pH values the concentrations of catechins in tea
      decrease in time. In this presentation we used micellar electrokinetic
      chromatography to determine the real concentration of catechins between 0 and 60
      min after the tea was brewed.

PMID- 11521905
TI  - Characterization of highly sulfated cyclodextrins.
AB  - A class of highly sulfated cyclodextrins (HS-CDs) was developed for enantiomeric
      separation of chiral compounds by capillary electrophoresis (CE). The HS-CDs were
      produced by a facile single-step direct sulfation of cyclodextrin using sulfur
      trioxide-trimethylamine complex in dimethylformamide. Characterization of the HS
      CDs by electrospray ionization mass spectrometry and by CE using a well
      established indirect detection method indicated the species have very narrow
      heterogeneity in terms of degree of sulfation. Elemental analysis of the HS-alpha
      , beta- and gamma-CDs showed that the average sulfate contents were 11, 12, and
      13 per CD molecule, respectively. The 13C NMR of HS-CDs is consistent with the
      structural assignment of nearly complete sulfation at C-6 primary hydroxyl groups
      and partial sulfation at the C-2 secondary hydroxyls (>70%), while the C-3
      hydroxyls remain unsubstituted. Enantiomeric separation by CE using the HS-CDs as
      chiral selectors showed that HS-alpha-, beta- and gamma-CDs complement each other
      by exhibiting different chiral selectivities, resulting in resolution of many
      chiral neutral, acidic and basic compounds of greatly varying structural
      features. The part of HS-CD that interacts with the guest molecule during
      complexation and, therefore, the receiving end of the cyclodextrin hydrophobic
      bucket was surrounded with largely regiospecifically substituted C-2 sulfates and
      intact C-3 hydroxyls, both at the equatorial positions. Such global regiospecific
      structural arrangement in HS-CDs provides differential diasteroisomeric
      complexation is proposed to be the principal contributing factor in the resolving
      racemates.

PMID- 11521906
TI  - Electrophoretron: a new method for enhancing resolution in electrokinetic
      separations.
AB  - Two capillaries, each of which have different surface preparations on their
      inside walls, are joined together to form a closed loop, and electrodes are
      placed inside the two capillaries. When the loop is filled with liquid and a
      potential difference is applied between the two electrodes, a circulating flow of
      liquid is established inside the loop because the resistance to flow is unequal
      in going from one electrode to another in a clockwise versus a counterclockwise
      direction. Consequently, a sample injected into this device, which we call an
      electrophoretron, repeatedly circulates between the two electrodes and the
      capillary separation column becomes effectively one of unlimited length. On each
      cycle the separation between analytes with different mobilities increases, thus
      enhancing resolution of analytes having nearly the same mobilities. The operation
      of a prototype electrophoretron is demonstrated.

PMID- 11521907
TI  - Factorial design of electrolyte systems for the separation of fatty acids by
      capillary electrophoresis.
AB  - In this work, a capillary zone electrophoretic methodology using UV indirect
      detection (224 nm) for the analysis of fatty acids (FAs) in saponified oils is
      proposed. The electrolyte consisted of a 5 mmol l(-1) phosphate buffer, pH 7.
      containing 4 mmol l(-1) sodium dodecylbenzenesulfonate (SDBS) as chromophore, 4
      mmol l(-1) dimethyl-beta-cyclodextrin and 45% acetonitrile (ACN). The composition
      of the electrolyte was optimized by a 2(3) factorial design with triplicate at
      the central point. The design established practical concentration boundaries for
      SDBS and ACN. In a defined concentration range of 2-4 l(-1), SDBS can certainly
      be used as a chromophore for indirect detection without imparting excessive
      baseline noise. For ACN, a suitable interval of 45-55% was found to enhance FAs
      solubilization without overflowing the system with bubble formation and current
      interruption. Additionally, the design revealed the importance of dimethyl-beta
      cyclodextrin in the resolution of difficult pairs and its function as a
      solubilizing agent for long chain FAs. At the optimized conditions, nine FAs from
      C10 to C20, including mono- di- and tri-unsaturated C18 fatty acids were baseline
      separated in less than 10 min. The proposed method was applied to the separation
      of FAs in edible oils and polyunsaturated fatty acid enriched margarine.
      Additionally, spectral monitoring at 206 nm was used to confirm peak identity in
      the samples.

PMID- 11521908
TI  - Separation and direct UV detection of lanthanides complexed with pyridine-2
      carboxylic acid by capillary electrophoresis.
AB  - Separation and detection of lanthanides by capillary zone electrophoresis in the
      presence of pyridine-2-carboxylic acid (picolinic acid) as UV-absorbing
      complexing agent were investigated. The resolution of partially complexed
      positively charged complexes is improved by using two buffer ligands competing
      with picolinic acid for metal ions. When hydroxyisobutyric acid (HIBA) and formic
      acid are used together as competing ligands, this provides complete separation of
      all 14 lanthanides with good peak shapes. An on-column separation of 14
      lanthanides was achieved in only 9 min using 0.8 mmol/l picolinic acid, 10 mmol/l
      HIBA and 25 mmol/l formic acid at pH 4.7. Determination of lanthanide complexes
      was performed by direct detection at 210 nm. Detection limits (signal-to-noise
      ratio=3) are ca. 0.53-0.96 microg/ml.

PMID- 11521909
TI  - Bonded dimethylacrylamide as a permanent coating for capillary electrophoresis.
AB  - A method for coating capillaries for capillary electrophoresis with chemically
      bonded polydimethylacrylamide has been developed, and the properties of the
      capillaries have been evaluated. The coated capillaries provided high separation
      efficiency, 12 x 10(5) theoretical plates/m was obtained for cytochrome c. The
      electroosmotic flow at pH 8.0 was 10 x 10(-10) to 6 x 10(-10) m2 V(-1) s(-1). The
      coated capillaries were quite stable at high pH. At least 150 runs could be done
      at pH 10 without appreciable performance deterioration. The excellent performance
      of the coated capillaries was illustrated by separation of basic proteins, acidic
      proteins, 9-fluorenylmethyl chloroformate-derivatized neurotransmitter amino
      acids, peptide reference mixtures and peptides digested from a bacteria protein.

PMID- 11521910
TI  - Omega-iodoalkylammonium salts as permanent capillary silica wall modifiers.
      Comparative analysis of their structural parameters and substituent effects.
AB  - Following previous work on the modification and inversion of electroendoosmotic
      flow (EOF) of naked silica by a cyclic diamine [1-(4-iodobutyl)-1,4
      dimethylpiperazin-1-ium iodide] [J. Chromatogr. A 894 (2000) 53], the present
      report considerably expands previous data by describing additional compounds of
      the same series of omega-iodoalkylammonium salts. Four of them are able to
      instantaneously reverse the EOF, thus producing a cationic surface with a highly
      stable reverse EOF. All these compounds are believed to become covalently
      attached to the silica surface via alkylation occurring by nucleophilic
      substitution of ionized silanols on the silica wall by the omega-iodo
      functionality in the modifier. The unique advantage of such compounds, as
      compared to adsorbed polymers or oligoamine EOF quenchers, is that they are not
      needed any longer in the background electrolyte, after the initial conditioning
      step inducing the covalent bond. It is additionally demonstrated, by running a
      mixture of cinnamic acid compounds, that some of the omega-iodoalkylammonium
      salts can act as modulators of analyte migration, thus inducing separations of
      otherwise identical compounds, such as isomeric species. Such interactions can
      only occur when the analytes drift close to the silica wall, and must be rapidly
      reversible, since no peak tailing or broadening is experienced.

PMID- 11521911
TI  - Capillary electrophoresis study on the micellization and critical micelle
      concentration of sodium dodecyl sulfate. Influence of solubilized solutes.
AB  - The influence of solubilized solutes on the micellization and critical micelle
      concentration (CMC) of sodium dodecyl sulfate (SDS) were investigated by means of
      capillary electrophoresis (CE). Three different structural types of test solutes,
      including chloropyridines. chlorophenols and cephalosporins with different
      binding strength to SDS micelles, were selected in this study. The variations of
      the effective electrophoretic mobility of these solutes as a function of SDS
      concentration in the premicellar and micellar regions were analyzed.
      Interestingly, the results indicate that, in the presence of these solubilized
      solutes, the micellization of SDS may occur over a range of SDS concentration,
      with the aggregate size increasing over this range. Depending on the nature of
      solubilized solutes and the extent of the interactions between solubilized
      solutes and SDS micelles, the CMC value of SDS may vary significantly. The
      incorporation of solubilized solutes into SDS micelles to form mixed micelles is
      proposed to interpret the migration behavior of solubilized solutes in CE.

PMID- 11521912
TI  - Regulation of electroosmotic flow and electrophoretic mobility of proteins for
      concentration without desalting.
AB  - Proteins were concentrated and separated in 0.6% poly(ethylene oxide) (PEO)
      solution using a capillary filled with Tris-borate (TB) buffer prior to analysis
      and detected by laser-induced native fluorescence using a pulsed Nd:YAG laser.
      During the concentration and separation, PEO solution entered the capillary by
      electroosmotic flow. When proteins dissolved in high salts (phosphate-buffered
      saline) were separated using 0.6% PEO solution prepared in 200 mM TB buffer, pH
      9.0, the limits of detection (LODs) at signal-to noise ratios=3 for carbonic
      anhydrase (CA) and alpha-lactalbumin (alpha-lac) were on the levels of sub microM
      and microM, respectively. The LOD values compared to those obtained in 38 mM TB
      buffer were relatively high, which is likely due to salt quenching, Joule heating
      and poor stacking. To improve sensitivity for analysis of proteins in high
      conductivity media, two on-line concentration approaches without desalting were
      developed. When using a capillary filled with 1.5 M TB buffer, pH 10.0, and PEO
      solution prepared in 800 mM TB buffer, pH 9.0, the LOD values for CA and alpha
      lac were 13.8 nM and 126.0 nM, respectively, which were about 4.7 and 11.2-fold
      sensitivity enhancements compared to those obtained by a conventional
      hydrodynamic injection (30 cm height for 10 s), respectively. The sensitivity was
      further improved by injecting a short plug of low pH buffer after protein
      injection using a capillary filled with 1.5 M TB buffer, pH 10.0, and PEO
      solution prepared in 400 mM TB buffer, pH 9.0. A linear relationship between the
      peak height and the injection volume up to 0.81 microl was obtained and the LOD
      values for CA and alpha-lac were down to 4.7 and 37.8 nM.

PMID- 11521913
TI  - Recommendations for using fluoride to prevent and control dental caries in the
      United States. Centers for Disease Control and Prevention.
AB  - Widespread use of fluoride has been a major factor in the decline in the
      prevalence and severity of dental caries (i.e., tooth decay) in the United States
      and other economically developed countries. When used appropriately, fluoride is
      both safe and effective in preventing and controlling dental caries. All U.S.
      residents are likely exposed to some degree to fluoride, which is available from
      multiple sources. Both health-care professionals and the public have sought
      guidance on selecting the best way to provide and receive fluoride. During the
      late 1990s, CDC convened a work group to develop recommendations for using
      fluoride to prevent and control dental caries in the United States. This report
      includes these recommendations, as well as a) critical analysis of the scientific
      evidence regarding the efficacy and effectiveness of fluoride modalities in
      preventing and controlling dental caries, b) ordinal grading of the quality of
      the evidence, and c) assessment of the strength of each recommendation. Because
      frequent exposure to small amounts of fluoride each day will best reduce the risk
      for dental caries in all age groups, the work group recommends that all persons
      drink water with an optimal fluoride concentration and brush their teeth twice
      daily with fluoride toothpaste. For persons at high risk for dental caries,
      additional fluoride measures might be needed. Measured use of fluoride modalities
      is particularly appropriate during the time of anterior tooth enamel development
      (i.e., age <6 years). The recommendations in this report guide dental and other
      health-care providers, public health officials, policy makers, and the public in
      the use of fluoride to achieve maximum protection against dental caries while
      using resources efficiently and reducing the likelihood of enamel fluorosis. The
      recommendations address public health and professional practice, self-care,
      consumer product industries and health agencies, and further research. Adoption
      of these recommendations could further reduce dental caries in the United States
      and save public and private resources.

PMID- 11521914
TI  - Current concepts of respiratory insufficiency syndromes after fracture.
AB  - Initial diligent resuscitation of the multiply-injured patient, with early
      fixation of the major orthopaedic injuries, has significantly reduced the
      incidence of post-traumatic respiratory complications from the unacceptably high
      levels which were seen 20 years ago. With these improvements we may be entering
      an era in which the risk of these complications is independent of the orthopaedic
      injury and is determined largely by the severity of injury to other body systems
      or by the immune and physiological status of the patient. Substantive proof of
      any beneficial effect from modification of the timing and technique of fracture
      stabilisation will be difficult to achieve without large multicentre randomised
      trials. It is conceivable that these interventions have a negligible effect on
      outcome or may actually be detrimental. Unravelling the basic molecular and
      cellular pathogenic processes of ARDS and FES will lead to improved therapeutic
      strategies for the treatment of this condition. For the present, however, the
      evidence suggests that expedient and appropriate early treatment of fractures in
      most instances protects against the development of post-traumatic respiratory
      insufficiency. Currently, the best and most effective therapeutic tool of the
      practising orthopaedic/trauma surgeon is prevention.

PMID- 11521915
TI  - Choosing an outcome measure.

PMID- 11521916
TI  - The floating shoulder. A multicentre study.
AB  - The aim of this retrospective study was to review a series of patients with
      ipsilateral fractures of the neck of the scapula and of the clavicle. Between
      1991 and 1996 a total of 79 general and orthopaedic surgeons treated 46 patients
      with a floating shoulder in The Netherlands. The records and radiographs of these
      patients were studied. Of the 35 patients available for follow-up, 31 had
      initially been treated conservatively and four by operation; three underwent
      secondary reconstructive surgery. The mean Constant score for the 28 patients
      treated conservatively was 76 and for the seven treated operatively it was 71 at
      a mean follow-up of 35 months. In six of the 28 patients treated conservatively
      the glenoid was dislocated caudally at the end of treatment; they had a score of
      42. In the 22 patients without this dislocation the score was 85. We conclude
      that this rare injury is not inherently unstable and, in the absence of caudal
      dislocation of the glenoid, conservative treatment gives a good functional
      outcome.

PMID- 11521917
TI  - The translated two-part fracture of the proximal humerus. Epidemiology and
      outcome in the older patient.
AB  - We have undertaken a five-year prospective study of 126 translated two-part
      fractures of the proximal humerus and present an analysis of the epidemiology and
      of the factors which affect outcome in elderly patients. The fracture has a
      unimodal age distribution and rarely affects adults under the age of 50 years.
      Analysis showed that patients with two-part translated fractures of the surgical
      neck tended to be independent and relatively fit, despite the fact that their
      mean age was 72 years. Outcome was determined by the age of each patient and the
      degree of translation on the initial anteroposterior radiograph. Surgery did not
      improve the outcome, regardless of the degree of translation.

PMID- 11521918
TI  - Comminuted fractures of the olecranon.  Management by bone graft from the iliac
      crest and multiple tension-band wiring.
AB  - Between 1993 and 1999, we treated ten patients with comminuted fractures of the
      olecranon by multiple tension-band wiring and a graft from the iliac crest. Their
      mean age was 35 years (19 to 56). The mean follow-up was for 28.5 months (15 to
      46) and the mean time to union of the fractures was four months (3 to 7). No
      patient reported difficulties with activities of daily living or symptoms of
      instability of the elbow. The mean flexion was to 135 degrees (125 to 145) with a
      mean flexion contracture of 15 degrees (10 to 30). The mean pronation was 70
      degrees (60 to 80) and mean supination 79 degrees (70 to 90). Only three patients
      had mild pain and loss of strength. Five patients had excellent and five good
      results with a mean Broberg and Morrey index score of 94.5 points (84 to 100).
      Our results compare favourably with those previously reported and the technique
      is thought to be a practical alternative to plate fixation in fractures with
      extreme comminution.

PMID- 11521919
TI  - Scaphoid blood flow and acute fracture healing.  A dynamic MRI study with
      enhancement with gadolinium.
AB  - We have investigated whether assessment of blood flow to the proximal scaphoid
      can be used to predict nonunion in acute fractures of the scaphoid. We studied 32
      fractures of the scaphoid one to two weeks after injury, by dynamic fat
      suppressed T1-weighted gradient-echo MRI after the intravenous administration of
      gadopentetate dimeglumine (0.1 mmol/kg body-weight). Steepest slope values (SSV)
      and percentage enhancement values (%E) were calculated for the distal and
      proximal fragments and poles. All the fractures were treated by immobilisation in
      a cast, and union was assessed by CT at 12 weeks. Nonunion occurred in four
      fractures (12%), and there was no statistically significant difference between
      the proximal fragment SSV and %E values for the fractures which united and those
      with nonunion. The difference between the proximal pole SSV and %E values for the
      union and nonunion groups reached statistical significance (p < 0.05), but with
      higher enhancement parameters for the nonunion group. Our results suggest that
      poor proximal vascularity is not an important determinant of union in fractures
      of the scaphoid.

PMID- 11521920
TI  - Scattered radiation during fixation of hip fractures.  Is distance alone enough
      protection?
AB  - We measured the scattered radiation received by theatre staff, using high
      sensitivity electronic personal dosimeters, during fixation of extracapsular
      fractures of the neck of the femur by dynamic hip screw. The dose received was
      correlated with that received by the patient, and the distance from the source of
      radiation. A scintillation detector and a water-filled model were used to define
      a map of the dose rate of scattered radiation in a standard operating theatre
      during surgery. Beyond two metres from the source of radiation, the scattered
      dose received was consistently low, while within the operating distance that
      received by staff was significant for both lateral and posteroanterior (PA)
      projections. The routine use of lead aprons outside the 2 m zone may be
      unnecessary. Within that zone it is recommended that lead aprons be worn and that
      thyroid shields are available for the surgeon and nursing assistants.

PMID- 11521921
TI  - Computerised measurement of tibiofemoral alignment.
AB  - Tibiofemoral alignment has a direct correlation with the survival of total knee
      arthroplasty. Traditionally, it has been measured using a goniometer on
      radiographs. We describe new software which measures this alignment on scanned
      radiographs by automatically detecting bones in the image. Two surgeons used
      conventional methods and two clerical officers used the computerised routine to
      assess 58 radiographs of the knee on two occasions. There were no significant
      differences between any of the paired comparisons. The largest mean difference
      detected was 1.19 degrees. Across all comparisons, the mean correlation was
      0.755. A standardised routine for measuring tibiofemoral alignment was the
      greatest factor in reducing error in our study. These results show that non
      medical staff can reliably use the software to measure tibiofemoral alignment. It
      has the potential to measure all the parameters recommended by the Knee Society.

PMID- 11521922
TI  - All-polyethylene versus metal-backed and stemmed tibial components in cemented
      total knee arthroplasty. A prospective, randomised RSA study.
AB  - We studied the quality of fixation of the tibial component using
      radiostereometric analysis (RSA) in 40 patients who had undergone a cemented
      Freeman-Samuelson total knee arthroplasty. They were prospectively randomised to
      either a stemmed metal-backed (MB) or non-stemmed all-polyethylene (AP) tibial
      component. The articulating geometry of the implants was identical, as was the
      operative technique and the postoperative regime. The study showed no
      complications of fixation using AP tibial components, and the migration was the
      same as that of their metal-backed counterparts. There was no bony collapse or
      increased subsidence of any part of the tibial component or increased incidence
      of radiolucent lines in the knees with AP components. Most AP implants were
      stable between one and two years after surgery, a finding known to be of positive
      prognostic significance when predicting future aseptic loosening.

PMID- 11521923
TI  - Fracture of the proximal tibia six months after Fulkerson osteotomy.  A report of
      two cases.
AB  - The Fulkerson osteotomy has proved to be a reliable treatment for subluxation of
      the patella due to malalignment. Aggressive rehabilitation in the early
      postoperative period is unwise since the proximal tibia is weakened by the
      oblique osteotomy. Early weight-bearing and unrestricted activity have caused
      fractures in a few patients. Even late in the postoperative period the osteotomy
      may adversely influence the biomechanical properties of the proximal tibia. We
      describe two athletes who sustained a fracture of the proximal tibia, during
      recreational activities, six months after a Fulkerson osteotomy. Both had been
      bearing full weight for about ten weeks without complaint. Bony healing of the
      osteotomy had been demonstrated on plain radiographs at ten and at 12 weeks.
      After a Fulkerson osteotomy, jogging and activities which impose considerable
      impact force should be discouraged for at least nine to 12 months.

PMID- 11521924
TI  - Endoscopic reconstruction of the anterior cruciate ligament with quadrupled
      hamstring tendons. A correlation between MRI changes and restored stability of
      the knee.
AB  - A total of 30 patients who underwent endoscopic reconstruction of the anterior
      cruciate ligament using quadrupled hamstring tendons, through a single drill hole
      in the femur, had MRI 24 to 28 months after operation. In 18 patients the scans
      revealed that both the anterior and posterior portions of the graft ran in
      parallel from the inside of the femoral to the tibial tunnel. In 12, the
      posterior bundle had moved anteriorly and the anterior bundle could not be
      identified at the anterodistal border of the femoral tunnel. The mean difference
      in the anterior laxity, when compared with the contralateral knee, was 2.0+/-1.7
      mm and 4.3+/-2.8 mm for the two types, respectively. Damage to the anterior
      bundle may occur when using the endoscopic technique because of biomechanical
      disadvantages, including concentration of loading and repetitive bending stress
      in the anterior bundle at the opening of the femoral tunnel.

PMID- 11521925
TI  - Radiological features predictive of aseptic loosening in cemented Charnley
      femoral stems.
AB  - The radiological features of the cement mantle around total hip replacements
      (THRs) have been used to assess aseptic loosening. In this case-control study we
      investigated the risk of failure of THR as predictable by a range of such
      features using data from patients recruited to the Trent Regional Arthroplasty
      Study (TRAS). An independent radiological assessment was undertaken on Charnley
      THRs with aseptic loosening within five years of surgery and on a control group
      from the TRAS database. Chi-squared tests were used to test the probability of
      obtaining the observed data by chance, and odds ratios were calculated to
      estimate the strength of association for different features. Several features
      were associated with a clinically important increase (>twofold) in the risk of
      loosening, which was statistically significant for four features (p < 0.01).
      Inadequate cementation (Barrack C and D grades) was the most significant feature,
      with an estimated odds ratio of 9.5 (95% confidence interval 3.2 to 28.4, p <
      0.0001) for failure.

PMID- 11521926
TI  - Acute rupture of tendon Achillis. A prospective randomised study of comparison
      between surgical and non-surgical treatment.
AB  - In a prospective, randomised, multicentre study, 112 patients (99 men and 13
      women, aged between 21 and 63 years) with acute, complete rupture of tendo
      Achillis were allocated either to surgical treatment followed by early functional
      rehabilitation, using a brace, or to non-surgical treatment, with plaster
      splintage for eight weeks. The period of follow-up was for two years. Evaluation
      was undertaken by independent observers and comprised interviews, clinical
      measurements, isokinetic muscle performance tests, heel-raise tests and an
      overall outcome score. The rate of rerupture was 20.8% after non-surgical and
      1.7% after surgical treatment (p < 0.001). Surgical and non-surgical treatment
      produced equally good functional results if complications were avoided. However,
      the rate of rerupture after non-surgical treatment was unacceptably high.

PMID- 11521927
TI  - Subtalar distraction bone block arthrodesis.
AB  - This retrospective study analyses the results of subtalar bone block distraction
      arthrodesis used in the treatment of late complications of calcaneal fractures,
      acute severely comminuted fractures, nonunion (and malunion) of attempted
      subtalar arthrodeses, avascular necrosis of the talus, and club-foot deformity.
      Of 39 patients (41 feet) who had this procedure, 35 (37 feet) returned for follow
      up after a mean of 70 months (26 to 140). There were 24 men (25 feet) and 11
      women (12 feet) with a mean age of 41 years (16 to 63). Each completed a
      standardised questionnaire, based on the hindfoot-scoring system of the American
      Orthopaedic Foot and Ankle Society and were reviewed both clinically and
      radiologically. Of the 37 operations, 32 (87%) achieved union. The mean hindfoot
      score (maximum of 94 points) increased from 21.1 points (8 to 46) preoperatively
      to 68.9 (14 to 82) at the final follow-up. The mean talocalcaneal and calcaneal
      pitch angles were 20.5 degrees and 4.9 degrees before operation, 25.9 degrees and
      8.3 degrees immediately after, and 24.6 degrees and 7.7 degrees at the final
      follow-up, respectively. The mean talar declination angle improved from 6.5
      degrees (-10 to 22) before operation to 24.8 degrees (14 to 32) at the final
      follow-up. The mean talocalcaneal height increased from 68.7 mm before operation
      to 74.5 mm immediately after and 73.5 mm at the final follow-up. Of the 37
      arthrodeses available for review, 32 were successful; 29 patients (30
      arthrodeses) were satisfied with the procedure. Minimal loss of hindfoot
      alignment occurred when comparing radiographs taken immediately after operation
      and at final follow-up.

PMID- 11521928
TI  - Treatment of bone-marrow oedema of the talus with the prostacyclin analogue
      iloprost. An MRI-controlled investigation of a new method.
AB  - Bone marrow oedema syndrome of the talus is a rare cause of pain in the foot,
      with limited options for treatment. We reviewed six patients who had been treated
      with five infusions of 50 microg of iloprost given over six hours on five
      consecutive days. Full weight-bearing was allowed as tolerated. The foot score as
      described by Mazur et al was used to assess function before and at one, three and
      six months after treatment. The mean score improved from 58 to 93 points. Plain
      radiographs were graded according to the Mont score and showed grade-I lesions
      before and after treatment, indicating that no subchondral fracture or collapse
      had occurred. MRI showed complete resolution of the oedema within three months.
      We conclude that the parenteral administration of iloprost may be used in the
      treatment of this syndrome.

PMID- 11521929
TI  - Tuberculosis of the thoracic spine.  A classification based on the selection of
      surgical strategies.
AB  - In spinal tuberculosis MRI can clearly demonstrate combinations of anterior and
      posterior lesions as well as pedicular involvement. We propose a classification
      system, using information provided by MRI, to help to plan the appropriate
      surgical treatment for patients with thoracic spinal tuberculosis. We describe a
      series of 47 patients, divided into four groups, based on the surgical protocol
      used in the management. Group A consisted of patients with anterior lesions which
      were stable with no kyphotic deformity, and were treated with anterior
      debridement and strut grafting. Group B comprised patients with global lesions,
      kyphosis and instability who were treated with posterior instrumentation using a
      closed-loop rectangle with sublaminar wires, and by anterior strut grafting.
      Group C were patients with anterior or global lesions as in the previous groups,
      but who were at a high risk for transthoracic surgery because of medical and
      possible anaesthetic complications. These patients had a global decompression of
      the cord posteriorly, the anterior portion of the cord being approached through a
      transpedicular route. Posterior instrumentation was with a closed-loop rectangle
      held by sublaminar wires. Group D comprised patients with isolated posterior
      lesions which required posterior decompression only. An understanding of the
      extent of vertebral destruction can be obtained from MRI studies. This
      information can be used to plan appropriate surgery.

PMID- 11521930
TI  - Anterior spinal decompression in HIV-positive patients with tuberculosis.  A
      prospective study.
AB  - total of 39 HIV-infected adults with spinal tuberculosis underwent anterior
      spinal decompression for neurological deficit. Fresh-frozen allografts were used
      in 38 patients. Antituberculous drugs were prescribed for 18 months, but
      antiretroviral therapy was not used. Six patients died within two years of
      surgery. Neurological recovery and allograft incorporation were observed at
      follow-up at a mean of 38 months, although the CD4/CD8 ratios were reversed in
      all patients. Adequate preoperative nutritional support and compliance with
      antituberculous treatment are essential in ensuring a satisfactory outcome.

PMID- 11521931
TI  - Primary glenoid dysplasia.  A review of 12 patients.
AB  - We reviewed 12 patients with primary glenoid dysplasia. Ten were assessed
      clinically and two from case notes and radiographs. We identified two groups
      according to the age at onset of symptoms. The first (seven patients) consisted
      of boys and younger men, all of whom developed symptoms before the age of 40
      years. All four children were free from pain, whereas the three adults in this
      group had varying degrees of this. Four patients had symptoms of instability. The
      second group consisted of older men (five patients) all of whom had noted the
      onset of symptoms, in the form of pain and stiffness, after the age of 40 years.
      All five had radiological evidence of osteoarthritis. Although the four children
      in our study had minimal symptoms, all eight adults had ongoing shoulder pain and
      dysfunction, despite a specific rehabilitation programme. Four patients required
      surgery; one had posterior stabilisation for instability and three arthroplasties
      of the shoulder for osteoarthritis.

PMID- 11521932
TI  - Low-energy extracorporeal shock-wave treatment (ESWT) for tendinitis of the
      supraspinatus. A prospective, randomised study.
AB  - We have performed a controlled, randomised study to analyse the effects of low
      energy shock-wave therapy (ESWT) on function and pain in tendinitis of the
      supraspinatus without calcification. There were 20 patients in the treatment
      group and 20 in the control group. The former group received 6,000 impulses
      (energy flux density, 0.11 mJ/mm2) in three sessions after local anaesthesia. The
      control group had 6000 impulses of sham ESWT after local anaesthesia. The
      patients were examined at six and 12 weeks after treatment by an independent
      observer who evaluated the Constant score and level of pain. We found an increase
      in function and a reduction of pain in both groups (p < or = 0.001). Statistical
      analysis showed no difference between the groups for the Constant score and for
      pain. We therefore do not recommend ESWT for the treatment of tendinitis of
      supraspinatus.

PMID- 11521933
TI  - The benefits of using patient-based methods of assessment. Medium-term results of
      an observational study of shoulder surgery.
AB  - We carried out a prospective study of 93 patients undergoing surgery for
      conditions of the rotator cuff during 1994 and 1995. They were assessed before
      operation and after six months, and four years, using the patient-based Oxford
      Shoulder Score (OSS), the SF-36 questionnaire and the Constant shoulder score.
      The response rates were higher for the OSS and SF-36. The correlation
      coefficients were high (r > 0.5) between all scores at each stage of the study.
      While all scores improved substantially at six months, the Constant score was
      reduced significantly at four years. This did not correlate with the patients'
      judgement of the change in symptoms or of the success of the operation. Our study
      suggests that patient-based measures of pain and function can reliably assess
      outcomes in the medium term after surgery to the shoulder.

PMID- 11521934
TI  - Supracondylar extension fracture of the humerus in children. Manipulative
      reduction, immobilisation and fixation using a U-shaped plaster slab with the
      elbow in full extension.
AB  - We present a method of manipulative reduction, immobilisation and fixation using
      a U-shaped plaster with the elbow in extension for extension-type supracondylar
      fractures of the humerus in children. When the elbow is in full extension, both
      the extensor and the flexor muscles are neutralised during manipulative reduction
      and the carrying angle can be easily assessed thus preventing cubitus varus, the
      most common complication. In order to evaluate the efficiency of this method, we
      compared the clinical results of the new method with those of conventional
      treatment. In a group of 95 children who sustained an extension-type
      supracondylar fracture of the humerus, 49 were treated by the new method and 46
      by the conventional method, reduction and immobilisation in a plaster slab with
      the elbow in flexion. Reduction and immobilisation were easily achieved and
      reliably maintained by one manipulation for all the children treated by the new
      method. In 12 children treated by the conventional method, the initial reduction
      failed and in seven secondary displacement of the distal fragment occurred during
      the period of immobilisation in plaster. All required a second or third
      manipulation. Of the 46 children, 28 (60.9%) had developed cubitus varus at a
      mean follow-up of 4.6 years when treated by the conventional method. None of the
      children treated by the new method developed cubitus varus. The mean score,
      according to the Hospital for Special Surgery (HSS) elbow scoring system, was 91
      points using the new method and 78 with the conventional method. The results were
      statistically significant with regard to the incidence of cubitus varus and the
      elbow score (p < 0.01) suggesting that the new method is reliable and gives a
      satisfactory outcome.

PMID- 11521935
TI  - Systematic pinning of displaced extension-type supracondylar fractures of the
      humerus in children. A prospective study of 116 consecutive patients.
AB  - We report the results of 116 consecutive displaced extension supracondylar
      fractures of the elbow in children treated during the first two years after the
      introduction of the following protocol; closed reduction under general
      anaesthesia with fluoroscopic control and lateral percutaneous pinning using two
      parallel pins or, when closed reduction failed, open reduction and internal
      fixation by cross-pinning. Eight patients were lost to follow-up during the first
      postoperative year. The mean follow-up for the remaining 108 was 27.9 months (12
      to 47, median 26.5). At the final follow-up, using Flynn's overall modified
      classification, the clinical result was considered to be excellent in 99 patients
      (91.6%), good in five (4.6%) and poor in four (3.7%). All the poor results were
      due to a poor cosmetic result, but had good or excellent function. Technical
      error in the initial management of these four cases was thought to be the cause
      of the poor results. The protocol described resulted in good or excellent results
      in 96% of our patients, providing a safe and efficient treatment for displaced
      supracondylar fractures of the humerus even in less experienced hands.

PMID- 11521936
TI  - Function of the upper limb after surgery for obstetric brachial plexus palsy.
AB  - We reviewed a consecutive series of 33 infants who underwent surgery for
      obstetric brachial plexus palsy at a mean age of 4.7 months. Of these, 13 with an
      upper palsy and 20 with a total palsy were treated by nerve reconstruction. Ten
      were treated by muscle transfer to the shoulder or elbow, and 16 by tendon
      transfer to the hand. The mean postoperative follow-up was 4 years 8 months. Ten
      of the 13 children (70%) with an upper palsy regained useful shoulder function
      and 11 (75%) useful elbow function. Of the 20 children with a total palsy, four
      (20%) regained useful shoulder function and seven (35%) useful elbow function.
      Most patients with a total palsy had satisfactory sensation of the hand, but only
      those with some preoperative hand movement regained satisfactory grasp. The
      ability to incorporate the palsied arm and hand into a co-ordinated movement
      pattern correlated with the sensation and prehension of the hand, but not with
      shoulder and elbow function.

PMID- 11521937
TI  - The osteoclastogenic molecules RANKL and RANK are associated with periprosthetic
      osteolysis.
AB  - Extensive osteolysis adjacent to implants is often associated with wear particles
      of prosthetic material. We have investigated if RANKL, also known as
      osteoprotegerin ligand, osteoclast differentiation factor or TRANCE, and its
      natural inhibitor, osteoprotegerin (OPG), may be important in controlling this
      bone loss. Cells isolated from periprosthetic tissues containing wear particles
      expressed mRNA encoding for the pro-osteoclastogenic molecules, RANKL, its
      receptor RANK, monocyte colony-stimulating factor (M-CSF), interleukin (IL)
      1beta, tumour necrosis factor (TNF)alpha, IL-6, and soluble IL-6 receptor, as
      well as OPG. Osteoclasts formed from cells isolated from periprosthetic tissues
      in the presence and absence of human osteoblastic cells. When osteoclasts formed
      in the absence of osteoblastic cells, markedly higher levels of RANKL mRNA
      relative to OPG mRNA were expressed. Particles of prosthetic materials also
      stimulated human monocytes to express osteoclastogenic molecules in vitro. Our
      results suggest that ingestion of prosthetic wear particles by macrophages
      results in expression of osteoclast-differentiating molecules and the stimulation
      of macrophage differentiation into osteoclasts.

PMID- 11521938
TI  - The inhibitory effects of colchicine on cell proliferation and mineralisation in
      culture.
AB  - Colchicine is often used in the treatment of diseases such as familial
      Mediterranean fever (FMF) and gout. We have previously reported that patients
      with FMF who had colchicine on a daily basis and who had a total hip arthroplasty
      showed no heterotopic ossification after surgery. The mechanism by which
      colchicine causes this clinical phenomenon has never been elucidated. We
      therefore evaluated the effect of various concentrations of colchicine on cell
      proliferation and mineralisation in tissue culture, using rat and human cells
      with and without osteogenic potential. Cell proliferation was assessed by direct
      cell counts and uptake of (3H)thymidine, and mineralisation by measuring the
      amount of staining by Alizarin Red. Our findings indicate that concentrations of
      colchicine of up to 3 ng/ml did not affect cell proliferation but inhibition was
      observed at 10 to 30 ng/ml. Mineralisation decreased to almost 50%, which was the
      maximum inhibition observed, at concentrations of colchicine of 2.5 ng/ml. These
      results indicate that colchicine at low concentrations, of up to 3 ng/ml, has the
      capacity to inhibit selectively bone-like cell mineralisation in culture, without
      affecting cell proliferation. Further clinical and laboratory studies are
      necessary to evaluate the effects of colchicine on biological processes involving
      the proliferation of osteoblasts and tissue mineralisation in vivo, such as the
      healing of fractures, the formation of heterotopic bone and neoplastic bone
      growth.

PMID- 11521939
TI  - Diagnosis of the level of intradural rupture of the rootlets in transaction
      lesions of the brachial plexus.
AB  - The precise point of intradural rupture in preganglionic traction injuries to the
      brachial plexus has been a subject of controversy. In this study of avulsed roots
      we have shown that rupture occurs at varying levels. True avulsion of the root
      with attached spinal cord tissue was seen in two cases and in the remainder
      rupture was peripheral to the central-peripheral transition zone. We have further
      shown that corpora amylacea marked the boundary between tissue of the central and
      peripheral nervous systems. This observation provides a basis for renewed work
      towards the direct repair of intradural ruptures of the ventral and dorsal roots.

PMID- 11521940
TI  - Changes in proximal femoral strain after insertion of uncemented standard and
      customised femoral stems.  An experimental study in human femora.
AB  - We have compared the changes in the pattern of the principal strains in the
      proximal femur after insertion of eight uncemented anatomical stems and eight
      customised stems in human cadaver femora. During testing we aimed to reproduce
      the physiological loads on the proximal femur and to simulate single-leg stance
      and stair-climbing. The strains in the intact femora were measured and there were
      no significant differences in principal tensile and compressive strains in the
      left and right femora of each pair. The two types of femoral stem were then
      inserted randomly into the left or right femora and the cortical strains were
      again measured. Both induced significant stress shielding in the proximal part of
      the metaphysis, but the deviation from the physiological strains was most
      pronounced after insertion of the anatomical stems. The principal compressive
      strain at the calcar was reduced by 90% for the anatomical stems and 67% for the
      customised stems. Medially, at the level of the lesser trochanter, the
      corresponding figures were 59% and 21%. The anatomical stems induced more stress
      concentration on the anterior aspect of the femur than did the customised stems.
      They also increased the hoop strains in the proximomedial femur. Our study shows
      a consistently more physiological pattern of strain in the proximal femur after
      insertion of customised stems compared with standard, anatomical stems.

PMID- 11521941
TI  - Fractured neck of femur in black patients.

PMID- 11521942
TI  - Presentation of material during talks.

PMID- 11521943
TI  - Symptoms and signs of irritation of the brachial plexus in whiplash injuries.

PMID- 11521944
TI  - How should orthopaedic surgeons respond to unsolicited e-mail?

PMID- 11521945
TI  - Cytochemical analysis of acid phosphatase activity in the venom secretory cells
      of Bothrops jararaca.
AB  - A study of the histochemical reaction for acid phosphatase (AcPase) in venom
      gland secretory cells from Bothrops jararaca was done to investigate the
      distribution of lysosomes and related structures in stages of high- and low
      protein synthesis. From this analysis, it was expected to gain insight into the
      cellular pathway by which AcPase is secreted into the venom. Two subtypes of
      AcPase reactivities were detected in the venom gland secretory cells: one was
      found in lysosomes and related structures and in some trans-Golgi network (TGN)
      elements and reacts with beta-glycerophosphate (betaGP) as substrate; the other
      was found in secretory vesicles, apical plasmalemma, lysosomes and related
      structures, and in some TGN elements, and reacts with cytidine monophosphate
      (CMP). The results are compatible with the possibility that there is a secretory
      via for AcPase in the venom gland of B. jararaca and that the elements composing
      this pathway are noted only when CMP is used as substrate. Large autophagosomes
      reactive to both betaGP and to CMP were commonly observed in the basal region of
      the secretory cells, and they were more abundant in the glands during the stage
      of low activity of protein synthesis.

PMID- 11521946
TI  - Apoptotic bone cells may be engulfed by osteoclasts during alveolar bone
      resorption in young rats.
AB  - The alveolar bone is a suitable in vivo physiological model for the study of
      apoptosis and interactions of bone cells because it undergoes continuous, rapid
      and intense resorption/remodelling, during a long period of time, to accommodate
      the growing tooth germs. The intensity of alveolar bone resorption greatly
      enhances the chances of observing images of the extremely rapid events of
      apoptosis of bone cells and also of images of interactions between osteoclasts
      and osteocytes/osteoblasts/bone lining cells. To find such images, we have
      therefore examined the alveolar bone of young rats using light microscopy, the
      TUNEL method for apoptosis, and electron microscopy. Fragments of alveolar bone
      from young rats were fixed in Bouin and formaldehyde for morphology and for the
      TUNEL method. Glutaraldehyde-formaldehyde fixed specimens were processed for
      transmission electron microscopy. Results showed TUNEL positive round/ovoid
      structures on the bone surface and inside osteocytic lacunae. These structures-
      also stained by hematoxylin--were therefore interpreted, respectively, as
      osteoblasts/lining cells and osteocytes undergoing apoptosis. Osteoclasts also
      exhibited TUNEL positive apoptotic bodies inside large vacuoles; the nuclei of
      osteoclasts, however, were always TUNEL negative. Ultrathin sections revealed
      typical apoptotic images--round/ ovoid bodies with dense crescent-like chromatin-
      on the bone surface, corresponding therefore to apoptotic osteoblasts/lining
      cells. Osteocytes also showed images compatible with apoptosis. Large osteoclast
      vacuoles often contained fragmented cellular material. Our results provide
      further support for the idea that osteoclasts internalize dying bone cells; we
      were however, unable to find images of osteoclasts in apoptosis.

PMID- 11521947
TI  - Hyaluronan affects protein and collagen synthesis by in vitro human skin
      fibroblasts.
AB  - Given the importance of hyaluronan (HA) for the homeostasis of connective tissues
      during embryogenesis and aging and its role in tissue repair, the aim of the
      present study was to examine the effect of exogenous HA on the synthesis of total
      protein, collagen and HA by in vitro human dermal fibroblasts. With differences
      between different cell strains, HA, at concentrations between 0.5 and 1 microM,
      induced a significant decrease in total protein synthesised and secreted into the
      medium compared to controls (P < 0.05), and particularly in collagen (-40%; P <
      0.05). The ratios between collagen types I and III and between collagen types V
      and I were normal. Pulse and chase experiments showed that protein degradation
      was normal. The presence of exogenous HA did not affect HA synthesis. Data
      strongly indicate that a relatively high concentration of HA in the extracellular
      space, such as during development and in the first phases of tissue repair, would
      partially limit the deposition of the extracellular matrix, and of collagen in
      particular. This would suggest a role for HA in delaying tissue differentiation
      during embryogenesis and in preventing fibrosis and scar formation in fetus and
      in the early phases of wound healing.

PMID- 11521949
TI  - Changes with age in the Golgi apparatus of rabbit spinal ganglion neurons.
AB  - We studied the Golgi apparatus in spinal ganglion neurons of rabbits aged 12, 42
      and 79 months. We found no structural changes, no indications of fragmentation,
      no indications of peripheral displacement affecting this organelle with advancing
      age. The volume of the perikaryon increased significantly with age, whereas the
      total volume of the Golgi apparatus remained essentially constant. Hence the mean
      percentage of perikaryal volume occupied by the Golgi apparatus decreased with
      age. This decrease was only in very minor part a consequence of lipofuscin
      accumulation, so that the ratio between the total volume of the Golgi apparatus
      and the functionally active volume of cytoplasm decreased with age. This decrease
      could be related to the reduced neuronal metabolism that occurs during ageing. It
      is possible that the delivery to the axon of newly synthesized proteins destined
      for fast transport is one of the Golgi apparatus roles that decrease with age.
      Finally, we found that the age-related quantitative changes in the Golgi
      apparatus did not differ between large light and small dark neurons.

PMID- 11521948
TI  - Ultrastructure and functional versatility of hirudinean botryoidal tissue.
AB  - In leeches, the botryoidal tissue is composed of two different cell types-
      granular botryoidal cells and flattened endothelial-like cells--localized in the
      loose connective tissue between the gut and the body wall sac. We have observed
      that the botryoidal tissue undergoes functional and structural modifications in
      response to the different needs arising during the life-cycle of the animal. In
      healthy, untreated leeches, botryoidal cells are organized in cords or clusters,
      sometimes surrounding few, small lacunae. Conversely, in wounded animals we have
      observed the transition of the botryoidal tissue from cluster/cord-like
      structures to a hollow/tubular architecture, typical of pre-vascular structures.
      We have documented in botryoidal cell cytoplasm the presence of large calcium
      storage. Moreover, the cytoplasm of botryoidal cells was filled with granules of
      different form and size, containing iron or melanin, as tested by classic
      histochemical methods. The presence of elements like iron and calcium was
      confirmed by the well-established EDS analysis. In response to a surgical wound,
      botryoidal tissue cells changed their shape and formed new capillary vessels.
      Concurrently, botryoidal cells secreted iron from cytoplasmic granules into the
      new cavity: this secretory activity appeared to be related to intracellular
      calcium fluctuations. At the end of the angiogenic process, botryoidal cells lost
      their contact with the basal lamina and moved freely in the circulating fluid
      towards the lesioned area. Interestingly, circulating botryoidal cells were found
      to carry melanin in the wounded area. This function is probably involved in
      defense processes. Thus, we have shown that stimulated botryoidal tissue displays
      a variety of striking structural, secretory and defensive activities.

PMID- 11521950
TI  - Immunolocalization of cytochrome P450 aromatase in rat testis during postnatal
      development.
AB  - Aromatization of androgens into estrogens in rat testis is catalyzed by the
      microsomal enzyme cytochrome P450 aromatase. In this work, aromatase cellular
      site was investigated in prepuberal, peripuberal and postpuberal testis, from 10
      , 21- and 60-day-old rats respectively. Paraffin-embedded testis sections were
      processed for P450arom immunostaining using a rabbit polyclonal antiserum
      generated against purified human placental cytochrome P450 aromatase. Next,
      biotinylated anti-rabbit IgG was applied, followed by ABC/HRP/complex
      amplification with diaminobenzidine as chromogen. Prepuberal testis sections
      showed a strong immunoreactivity of aromatase in Sertoli cell cytoplasm while
      interstitial cells were immunonegative. In peripuberal testis sections,
      cytoplasmic immunoreaction was weak in Sertoli cells, but it was strong in
      spermatocytes and sporadic in Leydig cells. Postpuberal testis sections displayed
      a moderate aromatase immunoexpression in spermatocytes while a strong
      immunostaining was observed in round and elongated spermatids, as well as in
      Leydig cells. These results indicate a different age-dependence of aromatase
      localization in rat testicular cells during gonadal development. In particular,
      inside the seminiferous tubules, the aromatization site moves from Sertoli cells
      to late germ cells, suggesting a proliferative role of aromatase in prepuberal
      testis and its subsequent involvement in meiotic and post-meiotic germ cell
      maturation.

PMID- 11521951
TI  - Structure and ultrastructure of the ventral prostate of isogenic mice (C57B1/6J)
      submitted to chronic alcohol ingestion.
AB  - Morphological and functional alterations caused by chronic alcohol ingestion in
      testes and accessory sex organs have been studied both in man and in laboratory
      animals. The aim of the present study was to examine the possible occurrence of
      deleterious effects of chronic alcohol ingestion on the secretory epithelium of
      the ventral prostate of mice. Twenty-four adult male C57BL/6J mice were divided
      into three groups. The alcohol-treated group was allowed to drink only 6% (v/v)
      ethanol, the isocaloric group received a diet of water/sucrose with a calorie
      content equivalent to a 6% alcohol solution and the control group received water.
      Both groups were fed ad libitum with solid Purina rat chow. After 120 days,
      animals from each group were anesthetized with ethyl ether, weighed and processed
      for light and transmission electron microscopy. The results demonstrated
      reduction in the glandular epithelium cell height and disorganization of the
      Golgi complex. Moreover, abundant membrane-bound structures, most likely
      representing cytoplasmic material, were observed, as well as accumulation of
      dense bodies. Statistical analysis showed that bodyweight gain was similar for
      both groups. In conclusion, chronic alcohol ingestion has harmful effects on the
      secretory epithelium cells of the ventral lobe of the prostate of mice after 120
      days of treatment.

PMID- 11521952
TI  - Ultrastructural changes in granulosa cells and plasma steroid levels after
      administration of luteinizing hormone-releasing hormone in the Western painted
      turtle, Chrysemys picta.
AB  - In this study we investigated the effects of treatment by luteinizing hormone
      releasing hormone (LHRH) on the morphology and steroid release of ovarian tissues
      in the Western painted turtle, (Chrysemys picta). In Experiment I, four adult
      female turtles were injected with synthetic mammalian LHRH (i.p., 500 pg/g
      bodyweight) and four with saline 2-3 weeks prior to ovulation. Granulosa cells
      from LHRH-treated turtles vs controls contained both preovulatory follicles (16
      20 mm in diameter) and small follicles (0.5-1.00mm in diameter) with increased
      RER, free ribosomes and mitochondria with swollen cristae. An increase in the
      amount of cytoskeletal material (microfilaments) was observed in granulosa cells
      of the experimental turtles compared to the controls. Cytoplasmic extensions of
      the oocyte and granulosa cells were longer in the small follicles of treated
      animals, accounting for the observed increase in the thickness of the zona
      pellucida (ZP) over the controls. In Experiment II, administration of LHRH (i.p.)
      to 10 turtles during the same period triggered a substantial increase in plasma
      progesterone and estradiol-17beta levels over the 10 saline-injected controls.
      This supports the idea that in this species, as in mammals, steroidogenic
      activity in the ovarian follicles are under the control of the hypothalamic
      pituitary axis. The ultrastructure and hormonal levels of the experimental
      animals were typical of untreated turtles just prior to ovulation. In this
      species the development of follicles and steroidogenesis can be stimulated
      prematurely by a releasing hormone from a nonreptilian origin.

PMID- 11521953
TI  - H-7 and fetal calf serum (FCS) act synergistically to increase apoptosis in the
      KB line of human oral carcinoma cells.
AB  - There is a high incidence of oral squamous cell carcinoma (SCC) worldwide. The
      survival rate is among the lowest of the major cancers and has not improved
      significantly over the past two decades. The KB line of human oral carcinoma
      cells is a useful experimental system for studies of the biology of oral SCC. In
      a previous study, we reported inhibition of KB cell proliferation and stimulation
      of desmosome formation in confluent cultures treated with 20 microM H-7 (1-(5
      isoquinolinylsulfonyl)-2-methylpiperazine). In the present study, the effects of
      this protein kinase C (PKC) inhibitor on the survival of KB cells were
      investigated. Apoptotic cells were detected using a combination of Hoechst 33258
      nuclear stain, TUNEL technique and ultrastructural analysis. Our results
      indicated that H-7 significantly increased apoptosis in KB cells in a dose
      dependent manner. Maximal stimulation occurred at 100 microM, the highest dose of
      H-7 tested. Apoptotic cells exhibited nuclear fragmentation, chromatin
      condensation and apoptotic bodies. Interestingly, H-7 and fetal calf serum (FCS)
      acted synergistically to increase apoptosis in KB cells, suggesting that there is
      a serum activated subpopulation of H-7 target cells in the cultures. The
      underlying mechanism of activation remains to be elucidated. Our study suggests
      that the PKC inhibitor H-7 is a potentially useful cytostatic agent for oral
      carcinoma cells.

PMID- 11521954
TI  - Acid polysaccharides in the skeletal matrix and calicoblastic epithelium of the
      stony coral Mycetophyllia reesi.
AB  - Like many corals the skeletal organic matrix and associated epithelium of
      Mycetophyllia reesi is physico-chemically unstable to preparative procedures for
      electron microscopy. Ethanol cryofracture of mineralized and demineralized
      material is accompanied by delamination of tissue and skeleton. Filamentous algae
      occur in the interface and account for some but not all of the separation
      artifact. Transmission microscopy accompanied by decalcification requires
      embedment in glycerol jelly to preserve the skeletal organic matrix. Even then,
      the matrix is not fixed and is not retained within the gel using standard double
      fixation with or without tannic acid as an additive. Ruthenium red, in
      combination with osmium, prevents the matrix from physical disruption, although
      positional artifacts relative to the calicoblastic epithelium are still evident.
      Inclusion of other glycan precipitating agents in the fixative sequence (Alcian
      blue, iron diamine or the detergent cetylpyridinium chloride) are more useful in
      preserving an acid polysaccharide-rich, fibrillar, extracellular matrix after
      demineralization. This material is not observed in SEM preparations. The
      calicoblast cells appear to be the source of this extracellular material that
      also appears to contribute to the composition of the mineralizing matrix.
      Moreover, a hyaluronan-like substance appears to play a significant role in
      matrix structure as suggested by its degradation by hyaluronidase.

PMID- 11521955
TI  - Desmocytes in the calicoblastic epithelium of the stony coral Mycetophyllia reesi
      and their attachment to the skeleton.
AB  - Desmocytes scattered over the surface of the corallum of the scleractinian
      Mycetophyllia reesi attach the calicoblastic tissue to the skeleton. The
      structure of the desmocyte is generally consistent with that of other
      scleractinians except for their more rectangular profiles and greater size.
      However, the extent of attachment is distinctive, and the mode of attachment to
      mineral is described for the first time. The skeleton contains dual rows of
      interconnected pits between the septa, within and among which desmocytes form
      virtually uninterrupted sheets. Desmocytes terminate with hemidesmosomes that
      attach the epithelium to a fibrillar basal lamina. Fibrils extend from the basal
      lamina into the skeletal matrix anchoring tissue firmly to the skeleton. In
      addition, the basal lamina itself appears to be incorporated within the organic
      matrix during growth, partitioning the skeleton into compartments. Because the
      skeletal organic matrix is physicochemically labile during demineralization,
      these intraskeletal details cannot be observed unless polycationic dyes such as
      Ruthenium red or other glycan precipitating agents are employed in the fixative
      sequence.

PMID- 11521956
TI  - Nuclear bodies in the oocyte nucleus of ground beetles are enriched in snRNPs.
AB  - Within the oocyte nucleus of many insect species, a variable number of intensely
      stained spherical bodies occur. These nuclear bodies differ significantly from
      nucleoli and their precise role in nuclei has not been elucidated yet. I have
      examined some of the histochemical properties as well as the molecular
      composition of these structures in a representative of ground (carabid) beetles.
      I demonstrate, using molecular markers, that the nuclear bodies are composed of
      small nuclear RNAs and associated proteins, including p80 coilin. Hence, they
      correspond to Cajal bodies (= coiled bodies) described in somatic cell nuclei as
      well as oocyte germinal vesicles in plant and animal organisms. It is suggested
      that Cajal bodies in the carabid germinal vesicle serve as a storage site for
      splicing factors.

PMID- 11521957
TI  - Peculiar digestion patterns of sponge-associated zoochlorellae in the caddisfly
      Ceraclea fulva.
AB  - The caddisfly Ceraclea fulva feeds exclusively on the freshwater sponge Ephydatia
      fluviatilis. Sponge spicules are accumulated in the insect midgut and arranged
      perpendicularly to the longitudinal axis of its gut. The peritrophic membrane of
      the midgut is so thick that it prevents spicules from damaging the epithelium
      during their transit. The digestion process of the endocellular zoochlorellae,
      which are vehiculated by the sponge cells, was examined by transmission electron
      microscopy (TEM). Zoochlorellae were seen in the midgut lumen, close to the
      peritrophic membrane and in the underlying space. Discrete algal cells became
      evident in tight apposition to the brush border of the midgut cells and were
      enveloped by the microvilli. Digestion progressed to the final transformation of
      the organism into membrane-delimited vacuoles.

PMID- 11521958
TI  - A descriptive and quantitative study of the keratocytes of the corneal stroma of
      albino rabbits using transmission electron microscopy.
AB  - The present morphometric study was designed to assess the dimensions and shape of
      keratocytes and their nuclei by transmission electron microscopy, and to assess
      these features in relation to the stromal lamellae. Corneas from 10 albino
      rabbits were fixed in 2% glutaraldehyde in cacodylate buffer (pH 7.4, 300
      mOsm/kg) and embedded in Spurr's epoxy resin. Both transverse and coronal thin
      sections through the corneal stroma were prepared. The stromal lamellae had an
      average thickness of 2.45+/-1.15 microm. The average cell thickness of the
      keratocytes was 1.34+/-0.46 microm (range 0.49-4.76 microm), with the apparent
      cell thickness being related to the average anterior-posterior thickness of the
      adjacent lamellae (r = 0.424, P = 0.001)). The relative length and thickness of
      the cell nucleus, in transverse section, was measured to be 0.65+/-0.13 and
      0.76+/-0.10 of the cell body section respectively. As assessed by planimetry, the
      area of the keratocyte cell body viewed in coronal section was 292+/-118 microm2,
      with a nucleus-to-cytoplasm ratio of 0.437+/-0.295. The electron micrographs
      confirmed the presence of gap junctions between keratocyte cell processes, and
      the occasional presence of centrioles in the cells. Some keratocyte processes
      were observed to extend from one face of the lamellae to the other, suggesting
      anterior-to-posterior cell communication. These studies indicate that the
      keratocyte cell thickness is influenced by the physical pressure exerted by
      adjacent stromal lamellae. The cell nucleus, while a dominant feature in
      transverse section, has a normal size in relation to the cell cytoplasm when
      viewed in coronal section.

PMID- 11521959
TI  - DSM-IV learning disorders in 10- to 12-year-old boys with and without a parental
      history of substance use disorders.
AB  - This research examined whether learning disorders (LDs) among 10- to 12-year-old
      boys are related to a parental history of alcohol and other substance use
      disorders (SUDs). Subjects were boys with (SA+; n = 179) and without (SA-; n =
      203) a parental history of SUDs. LD diagnoses were made according to DSM-IV
      criteria using several standardized intelligence tests, and mother and teacher
      reports of academic and cognitive difficulties. The results indicated a higher
      rate of DSM-IV LDs in SA+ compared to SA- boys. This association remained
      significant after accounting for the effects of socioeconomic status and
      ethnicity. SA+ boys with a lower socioeconomic status had particularly high rates
      of LDs (15.3%). The results suggest that LDs are associated with a parental
      history of SUDs. SA+ children with lower SES may be at particularly high risk for
      cognitive and academic difficulties.

PMID- 11521960
TI  - Early elementary school-aged child attachment to parents: a test of theory and
      implications for intervention.
AB  - Child attachment to parents has been shown in the literature to reduce the
      likelihood of problem behaviors through enhancing resiliency. Research examining
      attachment and its relationship to antisocial behavioral outcomes in adolescents
      has been shaped largely by social control theorists who have theorized that
      attachment to prosocial others inhibits the expression of antisocial behavioral
      outcomes (Hirschi, 1969). This paper seeks to expand the literature by
      investigating the development of child attachment to parent(s) during the early
      elementary school years as specified theoretically by the social development
      model (Catalano & Hawkins, 1996). Using structural equation modeling, the results
      support the theoretical model as proposed by the social development model. School
      aged children's attachment to parents can be successfully predicted by constructs
      outlined in the social development model. Finally, implications for interventions
      that enhance child attachment to parent(s) are discussed.

PMID- 11521961
TI  - Understanding the links among school misbehavior, academic achievement, and
      cigarette use: a national panel study of adolescents.
AB  - Relations among academic achievement, school bonding, school misbehavior, and
      cigarette use from 8th to 12th grade were examined in two national panel samples
      of youth (n = 3056). A series of competing conceptual models developed a priori
      was tested using structural equation modeling (SEM). The findings suggest that
      during middle adolescence the predominant direction of influence is from school
      experiences to cigarette use. School misbehavior and low academic achievement
      contribute to increased cigarette use over time both directly and indirectly. Two
      group SEM analyses involving two cohorts-gender and ethnicity- revealed that our
      findings are robust. In addition, comparisons between high school dropouts and
      nondropouts and between eighth-grade cigarette use initiators and nonusers
      revealed few differences in direction or magnitude of effects. Results suggest
      that prevention programs that attempt to reduce school misbehavior and academic
      failure, as well as to help students who misbehave and have difficulty in school
      constructively avoid negative school- and health-related outcomes, are likely to
      be effective in reducing adolescent cigarette use.

PMID- 11521963
TI  - Studies on effects of dietary fatty acids as related to their position on
      triglycerides.
AB  - This article reviews published literature on how the stereospecific structure of
      dietary triglycerides may affect lipid metabolism in humans. Animal studies have
      shown enhanced absorption of fatty acids in the sn-2 position of dietary
      triglycerides. Increasing the level of the saturated fatty acid palmitic acid in
      the sn-2 position (e.g., by interesterification of the fat to randomize the
      positions of the fatty acids along the glycerol backbone) has been shown in
      rabbits to increase the atherogenic potential of the fat without impacting levels
      of blood lipids and lipoproteins. In contrast, enhancing the level of stearic
      acid in the sn-2 position has not been found to affect either atherogenic
      potential or levels of blood lipids and lipoproteins in rabbits. Fatty acids
      other than palmitic and stearic have not been studied systematically with respect
      to possible positional effects. A limited number of human studies have shown no
      significant effects of interesterified fats on blood lipid parameters. However,
      it is unknown whether modifying the stereospecific structure of dietary
      triglycerides would affect atherogenicity or other long-term health conditions in
      humans. It is possible that incorporation of palmitic acid into the sn-2 position
      of milk fat is beneficial to the human infant (as a source of energy for growth
      and development) but not to human adults. Additional research is needed to
      determine whether processes like interesterification, which can be used to alter
      physical parameters of dietary fats (e.g., melting characteristics), may result
      in favorable or unfavorable long-term effects in humans.

PMID- 11521964
TI  - Dietary supplementation with conjugated linoleic acid increased its concentration
      in human peripheral blood mononuclear cells, but did not alter their function.
AB  - The purpose of this study was to examine if conjugated linoleic acid (CLA)
      supplementation of diets would alter fatty acid (FA) composition and function of
      peripheral blood mononuclear cells (PBMC). Seventeen women, 20-41 yr,
      participated in a 93-d study conducted at the Metabolic Research Unit. The same
      diet (19, 30, and 51% energy from protein, fat, and carbohydrate, respectively)
      was fed to all subjects throughout the study. Seven subjects (control group)
      supplemented their diet with six daily capsules (1 g each) of placebo oil
      (sunflower) for 93 d. For the other 10 subjects (CLA group), the supplement was
      changed to an equivalent amount of Tonalin capsules for the last 63 d of the
      study. Tonalin provided 3.9 g/d of a mixture of CLA isomers (trans-10,cis-12,
      22.6%; cis-11,trans-13, 23.6%; cis-9,trans-11, 17.6%; trans-8,cis-10, 16.6%;
      other isomers 19.6%), and 2.1 g/d of other FA. PBMC isolated on study days 30 and
      90 were used to assess intracellular cytokines by flow cytometry, secreted
      cytokines, and eicosanoid by enzyme-linked immonosorbent assay, and FA
      composition by gas-liquid chromatography. After supplementation, total CLA
      concentration increased from 0.012 to 0.97% (P < 0.0001) in PBMC lipids, but it
      did not significantly alter the concentration of other FA. CLA supplementation
      did not alter the in vitro secretion of prostaglandin E2, leukotriene B4,
      interleukin-1beta (IL-1beta), or tumor necrosis factor alpha (TNFalpha) by PBMC
      simulated with lipopolysaccharide, and the secretion of IL-2 by PBMC stimulated
      with phytohemagglutinin. Nor did it alter the percentage T cells producing IL-2,
      interferon gamma, and percentage of monocytes producing TNFalpha. The
      intracellular concentration of these cytokines was also not altered. None of the
      variables tested changed in the control group. Our results show that CLA
      supplementation increased its concentration in PBMC lipids, but did not alter
      their functions.

PMID- 11521962
TI  - The importance of neurobiological research to the prevention of psychopathology.
AB  - There is both a biological and environmental component to the neural substrates
      for various forms of psychopathology. Brain dysfunction itself not only
      constitutes a formidable liability to psychopathology, but also has an impact on
      environmental and social responses to the individual, compounding the risk for an
      adverse outcome. Environmental conditions, such as social and physical stimulus
      deprivation, poverty, traumatic stress, and prenatal drug exposure, can further
      compromise brain function in the context of existing liabilities. The
      relationship between genetic and environmental processes is interactive, fluid,
      and cumulative in their ability to influence an individual's developmental
      trajectory and alter subsequent behavioral outcomes. Given the codependent
      relationship between these processes, brain function is now believed to be
      malleable via manipulations of the environment in ways that may decrease
      liability for psychopathology. Research that explores these relationships and
      ways in which interventions can redirect this developmental track may
      substantially advance both the science and practice of prevention. Studies
      attempting to isolate the neurobiological effects of socioenvironmental factors
      are reviewed, implications for intervention strategies are discussed, and a
      future research agenda is proposed to provide greater insight into specific brain
      environment relationships. Armed with this knowledge, prevention scientists may
      eventually design programs that directly target these effects to reverse or
      attenuate negative outcomes.

PMID- 11521965
TI  - Fatty acid content of plasma lipids and erythrocyte phospholipids are altered
      following burn injury.
AB  - The objective of this study was to examine compositional and quantitative changes
      in fatty acids of plasma components and red blood cell phospholipids (PL)
      immediately following and during recovery from burn injury. Subjects (n = 10)
      with >10% total body surface area burn had blood drawn at specific timepoints (0
      to >50 d) following burn injury. Fatty acid composition of red blood cell PL and
      plasma PL, cholesteryl esters (CE), and triglycerides was determined using gas
      liquid chromatography after separating each fraction from extracted lipids by
      thin-layer chromatography. Total plasma PL and CE in burn patients were lower
      than in healthy control subjects with reduced 20:4n-6, n-6, and n-3 fatty acids
      and higher levels of monounsaturated and saturated fatty acids early after burn.
      CE levels remained half that of healthy control values up to 50 d post-burn. Red
      blood cell PL had decreased 20:4n-6 content and profiles similar to that of an
      essential fatty acid deficiency early after burn. These results suggest an
      impairment in lipoprotein and polyunsaturated fatty acid metabolism in the early
      post-burn period. Lower levels of 20:4n-6 and n-3 fatty acids in every plasma
      fraction suggest increased use of these fatty acids for wound healing and immune
      function following burn injury. Further work is needed to determine the ability
      of burn patients to utilize essential fatty acids in order to design nutritional
      intervention that promotes wound healing and immunological functions consistent
      with recovery in these patients.

PMID- 11521966
TI  - Regulation of intestinal apolipoprotein A-I synthesis by dietary
      phosphatidylcholine in newborn swine.
AB  - Phospholipid (PL) from both dietary sources and biliary secretions may be
      important in the regulation of intestinal apolipoprotein (apo) synthesis. We
      previously demonstrated the up-regulation of apo A-I secretion by
      phosphatidylcholine (PC) in a newborn piglet intestinal epithelial cell line. We
      hypothesized that dietary PC increases small intestinal apo A-I synthesis in vivo
      in the newborn piglet. Two-day-old female swine were fed by gavage for 48 h.
      Diets consisted of a formula containing 51% of calories as triacylglycerol
      providing 180 kcal/kg/24 h. The experimental group (+PC, n = 7) received 1 g/L
      added soybean PC, and the control group (-PC, n = 7) received no added PC. At the
      end of the study period, jejunal apo A-I, B, and A-IV synthesis was measured, and
      apo A-I mRNA levels were quantitated. Jejunal mucosal PL content and serum lipids
      and apo B and A-I levels were measured. Jejunal apo A-I synthesis was almost
      twice as high in the +PC group as compared to the -PC group with no difference in
      apo A-I mRNA levels. Jejunal content of PL was higher in the +PC group than in
      the -PC group. There were no differences in jejunal apo B and A-IV synthesis or
      serum levels of lipids and apo-lipoproteins between the two groups. Dietary PC
      supplementation in newborn swine up-regulated jejunal apo A-I synthesis. Apo A-IV
      synthesis, which is sensitive to fatty acid flux, was not significantly
      increased, which suggests a specific effect of PC on apo A-I synthesis. Lumenal
      PC may be important in the regulation of intestinal apo A-I synthesis in the
      neonate.

PMID- 11521967
TI  - Studies of phospholipid metabolism, proliferation, and secretion of stably
      transfected insulinoma cells that overexpress group VIA phospholipase A2.
AB  - A cytosolic 84 kDa Group VIA phospholipase A2 (iPLA2beta) that does not require
      Ca2+ for catalysis was cloned from Chinese hamster ovary (CHO) cells, murine
      P388D1 cells, pancreatic islet beta-cells, and other sources. Proposed iPLA2beta
      functions include participation in phosphatidylcholine (PC) homeostasis by
      degrading excess PC generated in CHO cells that overexpress CTP:phosphocholine
      cytidylyltransferase (CT), which catalyzes the rate-limiting step in PC
      biosynthesis; participation in biosynthesis of arachidonate-containing PC species
      in P388D1 cells by generating lysophosphatidylcholine (LPC) acceptors for
      arachidonate incorporation; and participation in signaling events in insulin
      secretion from islet beta-cells. To further examine iPLA2beta functions in beta
      cells, we prepared stably transfected INS-1 insulinoma cell lines that
      overexpress iPLA2beta activity eightfold compared to parental INS-1 cells or to
      INS-1 cells transfected with an empty retroviral vector that did not contain
      iPLA2beta cDNA. The iPLA2beta-overexpressing cells exhibit a twofold increase in
      CT activity compared to parental cells but little change in rates of [3H]choline
      incorporation into or disappearance from PC. Electrospray ionization (ESI) tandem
      mass spectrometric measurements indicate that iPLA2beta-overexpressing cells have
      1.5-fold higher LPC levels than parental INS-1 cells but do not exhibit increased
      rates of [3H]arachidonate incorporation into phospholipids, and incorporation is
      unaffected by a bromoenol lactone (BEL) suicide substrate inhibitor of iPLA2beta.
      The rate of appearance of arachidonate-containing phosphatidylethanolamine
      species visualized by ESI mass spectrometry is also similar in iPLA2beta
      overexpressing and parental INS-1 cells incubated with supplemental arachidonic
      acid, and this process is unaffected by BEL. Compared to parental INS-1 cells,
      iPLA2beta-overexpressing cells proliferate more rapidly and exhibit amplified
      insulin secretory responses to a protein kinase C-activating phorbol ester,
      glucose, and a cAMP analog. These findings suggest that iPLA2beta plays a
      signaling role in beta-cells that differs from housekeeping functions in PC
      biosynthesis and degradation in P388D1 and CHO cells.

PMID- 11521968
TI  - Metabolism of an oxysterol, 7-ketocholesterol, by sterol 27-hydroxylase in HepG2
      cells.
AB  - 7-Ketocholesterol (7K) is a quantitatively important oxysterol in both
      atherosclerotic lesions and macrophage foam cells. We reported recently that
      radiolabeled 7K delivered to rodents in a modified lipoprotein or chylomicron
      remnant-like emulsion, both cleared predominantly by the liver, was rapidly
      excreted into the intestine as water-soluble products, presumably bile acids.
      Herein, we aimed to elucidate the early or initial reactions in 7K metabolism.
      The hypothesis was tested that sterol 27-hydroxylase, a mitochondrial cytochrome
      P450 and the first enzyme of the acidic bile acid pathway, is responsible for the
      initial metabolism of 7K by HepG2 cells, a human hepatoblastoma cell-line. The 27
      hydroxylated product of 7K (27OH-7K) was shown to be the initial, lipid-soluble
      product of 7K metabolism. It was produced in mitochondrial incubations and whole
      cells and was readily released into the media from cells. Intact cells generated
      metabolites of 7K that had undergone conversion from lipid-soluble precursors to
      water-soluble products rapidly and extensively. Their production was ablated with
      cyclosporin A, a sterol 27-hydroxylase inhibitor. Furthermore, we demonstrated
      the effectiveness of two novel selective inhibitors of this enzyme, GW273297X and
      GI268267X. These inhibitors also ablated the production of water-soluble products
      by cells; and the inhibitor of choice, GW273297X, decreased the production of
      27OH-7K in mitochondrial preparations. This is the first study to demonstrate
      that sterol 27-hydroxylase plays an important role in the metabolism of
      oxysterols such as 7K in liver cells.

PMID- 11521969
TI  - Incorporation of alpha-linolenic acid and linoleic acid into human respiratory
      epithelial cell lines.
AB  - Animal and human studies designed to examine the effects of alpha-linolenic acid
      (ALA) and linoleic acid (LA) supplementation on the fatty acid composition of
      plasma and tissues have demonstrated a marked difference in incorporation into
      phospholipids of these 18-carbon precursors of the long-chain polyunsaturates.
      Whereas tissue phospholipid levels are linearly related to dietary ALA and LA,
      the levels of tissue LA can be 10-fold higher than tissue ALA even when dietary
      levels are equivalent. There is some dispute whether this disparity is due to ALA
      being more rapidly metabolized to its products or substantially oxidized by the
      liver, or whether LA but not ALA is readily incorporated into cellular
      phospholipids. We examined the level of incorporation of polyunsaturated fatty
      acids into human respiratory epithelial cell lines (A549, 16HBE) by determining
      the dose-dependent incorporation of ALA and LA as free fatty acid (5-150 microg
      FFA/mL). Cell membrane phospholipid ALA and LA were both increased up to
      approximately 20-30% total fatty acids, with a concomitant decrease predominantly
      in monounsaturated membrane fatty acids, before significant toxicity was observed
      (50 microg/mL). Our data support the concept that rather than any inherent
      inability by human cells to incorporate ALA into membrane phospholipids, the lack
      of ALA content in human and animal tissues in vivo is due to the rapid metabolism
      or oxidation of this fatty acid in the liver.

PMID- 11521970
TI  - Modeling of alpha-tocopherol loss and oxidation products formed during
      thermoxidation in triolein and tripalmitin mixtures.
AB  - The degradation of alpha-tocopherol and the formation of alpha-tocopherol and
      triacylglycerol oxidation products at high temperatures (150-250 degrees C) over
      a heating period (0-4 h) for a model system ranging between triolein and
      tripalmitin were modeled by use of an experimental design. The oxidation products
      of alpha-tocopherol formed under these conditions were alpha-tocopherolquinone (1
      .4-7.7%) and epoxy-alpha-tocopherolquinones (4.3-34.8%). The results indicate a
      very high susceptibility of alpha-tocopherol to capture peroxyl radicals upon
      oxidation, leading to the formation of polar tocopherol oxidation products. Both
      alpha-tocopherolquinone and epoxy-alpha-tocopherolquinones were not stable upon
      prolonged heating and were further degraded to other unknown oxidation products.
      The kinetics of alpha-tocopherol oxidation were significantly influenced by the
      triolein/tripalmitin ratio. By increasing the level of triacylglycerol
      unsaturation the rate of alpha-tocopherol recovery after heating increased
      significantly from 2.2 to 44.2% whereas in the meantime triacylglycerol
      polymerization increased from 0 to 3.7%.

PMID- 11521971
TI  - The occurrence of geometric polyprenol isomers in the rubber-producing plant,
      Eucommia ulmoides Oliver.
AB  - The chain length and geometric isomerism of polyprenols from Eucommia ulmoides
      Oliver were analyzed using supercritical fluid chromatography. After intensive
      effort to establish separation conditions for geometric isomers, a phenyl-bonded
      silica gel-packed column was found that cleanly separated poly-trans and -cis
      prenols. The presence of long-chain poly-trans prenols (>9 mers) was confirmed
      for the first time in plants. Trans isomers were found in the leaf, seed coat,
      and root, but not in the bark and seed. Poly-trans prenols in this plant may act
      as intermediates for trans-polyisoprene biosynthesis.

PMID- 11521972
TI  - Positional distribution of highly unsaturated fatty acids in triacyl-sn-glycerols
      of Artemia nauplii enriched with docosahexaenoic acid ethyl ester.
AB  - This paper presents the positional distribution of fatty acids in triacyl-sn
      glycerols (TAG) of Artemia nauplii used in aquaculture as a live food for marine
      fish larvae. The nauplii were enriched with docosahexaenoic acid (DHA) ethyl
      ester (EE) in the form of gelatin-acacia microcapsules for 4, 18, and 24 h. TAG
      of the initial, enriched, and unenriched Artemia nauplii were subjected to
      stereospecific analysis. A remarkable increase of DHA content in the enriched
      Artemia TAG confirmed the view that DHA-EE is effectively assimilated and
      incorporated into the TAG fraction of Artemia nauplii. TAG of the nauplii
      enriched with 25 mg/L of DHA-EE contained DHA at concentrations of 5.9-6.8, 4.3
      6.0, and 14.3-22.3 mol% in the sn-1, sn-2, and sn-3 positions, respectively. When
      the nauplii were enriched with 100 mg/L of DHA-EE, proportions of DHA in the sn
      1, sn-2, and sn-3 positions were 5.2-8.6, 3.9-6.0, and 12.2-25.4 mol%,
      respectively. In all of the enriched Artemia, DHA was preferentially located in
      the sn-3 position followed in sequence by the sn-1 and sn-2 positions. The lower
      content of DHA in the sn-1 and sn-2 positions was consistent with low content of
      this acid in 1,2-diacyl-sn-glycerophospholipids. When fish larvae are reared on
      Artemia nauplii enriched with EE-type DHA oil, the larvae feed on DHA esterified
      in TAG with a positional distribution pattern similar to that of marine mammals
      (sn-3 >> sn-1 > sn-2) rather than that of fish or marine invertebrates (sn-2 >>
      sn-3 > sn-1).

PMID- 11521973
TI  - Determination of stereochemical configuration of the glycerol moieties in
      glycoglycerolipids by chiral phase high-performance liquid chromatography.
AB  - This study reports a simple and sensitive method for determining the absolute
      configuration of the glycerol moieties in glycoglycerolipids. The method is based
      on chiral phase high-performance liquid chromatography (HPLC) separations of
      enantiomeric di- and monoacylglycerols released from glycosyldi- and
      monoacylglycerols, respectively, by periodate oxidation followed by
      hydrazinolysis. The released di- and monoacylglycerols were chromatographed as
      their 3,5-dinitrophenylurethane (3,5-DNPU) and bis(3,5-DNPU) derivatives,
      respectively. The derivatives were separated on two chiral phases of opposite
      configuration, (R)- and (S)-1-(1-naphthyl)ethylamine polymers for diacylglycerols
      and N-(R)- -(1-naphthyl)ethylaminocarbonyl-(S)-valine and N-(S)-1 -(1
      naphthyl)ethylamino-carbonyl-(R)-valine for monoacylglycerols. Clear enantiomer
      separations, which permit the assignment of the glycerol configuration, were
      achieved for sn-1,2(2,3)-diacyl- and sn-1(3)-monoacylglycerols generated from
      linseed oil triacylglycerols by partial Grignard degradation on all the chiral
      stationary phases employed. Using the method, we have determined the glycerol
      configuration in the glycosyldiacylglycerols (monogalactosyl-, digalactosyl-, and
      sulfquinovosyldiacylglycerols) and glycosylmonoacylglycerols (monogalactosyl-,
      digalactosyl-, and sulfoquinovosylmonoacylglycerols) isolated from spinach leaves
      and the coralline red alga Corallina pilulifera. The results clearly showed that
      the glycerol moieties in all the glycoglycerolipids examined have S-configuration
      (sn-1,2-diacyl- and sn-1-monoacylglycerols). The new method demonstrates that
      chiral phase HPLC provides unambiguous information on the configuration of the
      glycerol backbone in natural glycosyldi- and monoacylglycerols, and that the two
      step liberation of the free acylglycerols does not compromise glycerol chirality.

PMID- 11521974
TI  - Quantification of key odorants formed by autoxidation of arachidonic acid using
      isotope dilution assay.
AB  - Six odor-active compounds generated by autoxidation of arachidonic acid (AA) were
      quantified by isotope dilution assay (IDA), i.e., hexanal (1), 1-octen-3-one (2),
      (E,Z)-2,4-decadienal (3), (E,E)-2,4-decadienal (4), trans-4,5-epoxy-(E)-2-decenal
      (5), and (E,Z,Z)-2,4,7-tridecatrienal (6). Compound 1 was the most abundant
      odorant with about 700 mg/100 g autoxidized AA, which corresponds to 2.2 mol%
      yield. Based on the odor activity values (ratio of concentration to odor
      threshold), odorants 3 (fatty) and 5 (metallic) showed the highest sensory
      contribution followed by 1 (green), 2 (mushroom-like), 6 (egg white-like), and 4
      (fatty). For the first time, reliable quantitative results are reported for
      odorants 1-6 in autoxidized AA, in particular odorant 6, which is a
      characteristic compound found in autoxidized AA. Synthesis of deuterated 6,
      required for IDA, is described in detail. The formation of odorants 1-6 by
      autoxidation of AA is discussed with respect to the quantitative data.

PMID- 11521975
TI  - Tuberculous pleurisy: an unusual complication during treatment of Crohn disease
      with azathioprine.
AB  - A patient is presented with Crohn disease who developed tuberculous pleurisy
      while treated with azathioprine. The prevalence of opportunistic infections is
      discussed in patients with inflammatory bowel disease and treated with
      immunosuppressive regimes.

PMID- 11521976
TI  - Epidemiology of inflammatory bowel disease in Heraklion, Crete.

PMID- 11521977
TI  - Cyclooxygenase-2 in carcinogenesis of the gastrointestinal tract.

PMID- 11521978
TI  - Chronic oesophagitis in the cat.
AB  - BACKGROUND: Our understanding of the pathophysiology of gastro-oesophageal reflux
      disease (GERD) in man is limited. The aim of the present study was to establish a
      long-term (>1 year) animal model for reflux oesophagitis which would allow us to
      study various aspects of the development of chronic reflux oesophagitis. METHODS:
      Myotomy was carried out in the gastro-oesophageal junction in eight cats; seven
      other cats were sham-operated. Before the operation, and every 2 months
      thereafter, oesophagoscopy was carried out, biopsies were taken for histology,
      and manometry was performed to determine the lower oesophageal sphincter pressure
      (LESP). The cats were killed 1 year after the operation. RESULTS: The myotomy
      operation resulted in a significantly decreased LESP. In oesophageal biopsies
      from these cats, there was a varying degree of oesophagitis starting already 2
      months after surgery. In six of the eight myotomized cats there was hyperplasia
      of the stratum basale, and cardiac type metaplasia was observed in two cats. The
      control cats showed no significant changes in LESP or in the histology of the
      oesophagus. CONCLUSIONS: In cats followed for more than a year, myotomy in the
      gastro-oesophageal junction results in reflux oesophagitis similar to that seen
      in patients with chronic gastro-oesophageal reflux.

PMID- 11521979
TI  - Immunohistochemical markers for Barrett's esophagus and associations to
      esophageal Z-line appearance.
AB  - BACKGROUND: Data from previous studies on intestinal metaplasia at the
      gastroesophageal junction have been conflicting, which makes the diagnosis of
      Barrett's esophagus less obvious. This may partly be due to the lack of a
      reliable classification of the Z-line appearance. We previously proposed such a
      classification (the ZAP classification) that was shown to correlate with the
      prevalence of intestinal metaplasia. The use of different immunohistochemical
      techniques has increased in the study of intestinal metaplasia. In the present
      study our aim was to 1) evaluate the impact of different antibodies, namely
      cytokeratin (CK) 7, 13, and 20, CaCO3/73, and FBB2/29, in order to differentiate
      between Barrett's esophagus and cardia intestinal metaplasia, and 2) explore the
      staining patterns in different ZAP grades. METHODS: Thirty-nine specimens with
      intestinal metaplasia were compared--9 from Barrett's esophagus, 6 from cardia,
      and 24 from the Z-line. The Z-line specimens were evaluated with respect to ZAP
      grade. RESULTS: No differences were encountered regarding staining patterns for
      CK13 and CaCO3/73 in Barrett's esophagus and cardia. The staining pattern of
      CK7/20 was significantly different between Barrett's esophagus and cardia. CK7/20
      showed a rising frequency of Barrett's esophagus staining pattern with rising ZAP
      grade. CONCLUSION: CK7/20 is a feasible marker for Barrett's esophagus.
      Intestinal metaplasia in different ZAP grades differs regarding expression of
      immunohistochemical markers.

PMID- 11521980
TI  - Gastroesophageal acid reflux in patients with nutcracker esophagus.
AB  - BACKGROUND: Hypertensive esophageal contraction, called nutcracker esophagus
      (NE), is the most common motility abnormality associated with cardiac-like chest
      pain. However, its significance for the development of symptoms has been a matter
      of controversy for decades, and recently it has been suggested that NE might
      represent a primarily acid-related esophageal disorder. The frequency of acid
      related esophageal dysfunction is studied in an unselected group of patients with
      NE. METHODS: During the period March 1993 to June 1998, 572 consecutive patients
      underwent esophageal manometry and 24-h pH monitoring. RESULTS: A motility
      pattern consistent with NE was found in 45 subjects referred because of chest
      pain (n = 35), reflux dyspepsia only (n = 8) or epigastric pain (n = 2). Acid
      related esophageal dysfunction was noted in 30 (70%) of the NE patients; abnormal
      acid exposure time (n = 21), esophagitis (n = 2) or positive symptom index (n =
      7). In addition, an increased number of reflux episodes were found in another
      three subjects. NE was more prevalent in subjects referred for chest pain than in
      those referred for other symptoms (14.3% versus 4.5%; P < 0.0001) and,
      conversely, 78% of the patients with NE were referred because of chest pain.
      CONCLUSIONS: Various aspects of acid-related esophageal dysfunction occur
      frequently in patients with NE, suggesting that acid may play a role in the
      development of symptoms in NE. Nonetheless, given its association with chest
      pain, NE could be a marker of a subgroup of patients with acid reflux, distinct
      from other reflux patients.

PMID- 11521981
TI  - Insulin-like growth factor I accelerates gastric ulcer healing by stimulating
      cell proliferation and by inhibiting gastric acid secretion.
AB  - BACKGROUND: Given the importance of Insulin-Like Growth Factor I (IGF-I) to
      intestinal maintenance and the presence of IGF-I in salivary glands, we
      hypothesized that IGF-I participates in the healing of gastric ulcers. The aim of
      the study was to determine: 1) whether IGF-I applied locally would support
      gastric ulcer healing by increasing cell proliferation and 2) the effect of IGF-I
      on gastric acid secretion. METHODS: Gastric ulcers were induced with a cryoprobe.
      Immediately thereafter, IGF-I (0.4, 4.0 and 40 microg) or vehicle was infiltrated
      perifocally. In another group, animals received a daily dose of 40 micromol
      omeprazole subcutaneously. Ulcer healing was evaluated by ulcer size and
      histological examination at 7 days. Pentagastrin-stimulated gastric acid
      secretion was evaluated in conscious rats with gastric fistula, after IGF-I (400
      microg) had been injected intravenously. RESULTS: IGF-I significantly reduced
      ulcer size, but only at low doses (0.4 microg/kg body weight (BW), P = 0.008; 4
      microg/kg BW, P = 0.001). This effect was similar to omeprazole treatment.
      Histological examination after IGF-I administration showed increased cell
      proliferation, increased IGF-I content and down-regulated IGF-I receptors. The
      secretory studies demonstrated a significant decrease in gastric acid secretion
      30 min after IGF-I bolus injection (IGF-I: 53 +/- 11 microEq; vehicle: 116 +/- 5
      microEq; P=0.001), which lasted for more than 1 h. CONCLUSION: IGF-I stimulates
      gastric ulcer healing, stimulating cell proliferation and inhibiting gastric acid
      secretion.

PMID- 11521982
TI  - Increased risk of developing atrophic gastritis in patients infected with CagA+
      Helicobacter pylori.
AB  - BACKGROUND: To clarify the possible role of CagA positive (CagA+) Helicobacter
      pylori strains in the development of atrophic gastritis, the prevalence of
      antibodies to H. pylori and CagA (120 kD protein) was studied among subjects with
      atrophic and non-atrophic gastritis. METHODS: The study population was randomly
      selected among 12,252 Finnish men who were screened for atrophic corpus gastritis
      with serum pepsinogen I-assay (S-PGI). S-PGI level was used as a selection
      criterion. Group A consisted of 295 subjects with S-PGI <25 microg/l (low), group
      B of 320 subjects with S-PGI 25-100 microg/l (normal) and group C of 338 subjects
      with S-PGI >100 microg/l (high). Antibodies to H. pylori were measured with EIA
      and immunoblot analysis and antibodies to CagA with immunoblot analysis.
      Endoscopical and histological examinations were performed for 203 patients from
      group A. RESULTS: The prevalence of antibodies to H. pylori was significantly
      lower in group B than in groups A or C (P < 0.0001, chi-squared test). There was
      a significant association between the prevalence of antibodies to CagA and the
      lowered level of S-PGI (P < 0.0001, Jonckheere-Terpstra trend test). There was
      also a linear decrease in the prevalence of antibodies to CagA as the atrophic
      corpus gastritis became more severe (P < 0.0001, linear-by-linear trend test).
      CONCLUSION: The presence of antibodies to CagA seems to be associated with
      development of atrophic corpus gastritis.

PMID- 11521983
TI  - Treatment of non-ulcer dyspepsia: a meta-analysis of placebo-controlled
      prospective studies.
AB  - BACKGROUND: Dyspeptic symptoms are commonly reported complaints in clinical
      practice and are mostly the result of functional disorders. Empirical treatment
      with histamine H2-receptor blockers or gastroprokinetics for 2-4 weeks has
      frequently been proposed as first line management of these patients. The clinical
      trials which support the use of these agents, show a high variation in clinical
      success rate and benefit of these treatments. METHODS: The available clinical
      trials were evaluated, pooled where appropriate and subjected to a meta-analysis
      with the principal goal to provide valid treatment recommendations for patients
      with non-ulcer dyspepsia. In the present meta-analysis 19 studies on
      gastroprokinetics (cisapride, domperidone) and 10 studies on histamine H2
      receptor antagonists (cimetidine, ranitidine) were included. RESULTS: Based on
      these studies, a total of 1540 patients were evaluated for histamine H2-receptor
      antagonists (verum n = 786, placebo n = 754) and 1235 patients for
      gastroprokinetics (verum n = 616, placebo n = 619). The probability for treatment
      success compared to placebo was 0.2026 (0.1261; 0.2791) for histamine H2-receptor
      antagonists and 0.4029 (0.3042; 0.5069) for gastroprokinetics. CONCLUSIONS: Based
      on these data both treatments are significantly more effective than placebo in
      the symptomatic treatment of non-ulcer dyspepsia, with gastroprokinetics
      (cisapride, domperidone) being more effective than histamine H2-receptor
      antagonists (cimetidine, ranitidine).

PMID- 11521984
TI  - Dyspepsia in primary care: acid suppression as effective as prokinetic therapy. A
      randomized clinical trial.
AB  - BACKGROUND: While dyspeptic patients in primary care often receive empirical
      treatment with antisecretory drugs, a substantial number suffer from motility
      disturbances which may be associated with their complaints. We aimed to compare
      the effectiveness of treatment with antisecretory treatment with a prokinetic
      agent in uninvestigated dyspepsia. METHODS: 563 patients presenting dyspeptic
      complaints to the general practitioner with a low likelihood of organic (ulcer,
      reflux or malignant) disease, i.e. absence of alarm symptoms or a history of
      peptic ulcer disease or gastro-oesophageal reflux disease were included. They
      entered a randomized, double-blind trial of 4 weeks of ranitidine 150 mg bid
      compared with 4 weeks of cisapride 10 mg bid, with 3 months follow-up. Treatment
      failure was defined as no response to treatment or a relapse of symptoms within
      the follow-up period. Also studied were the effect on dyspepsia severity,
      response to treatment after 4 weeks, and time to relapse. RESULTS: For all
      randomized patients, the incidence of overall treatment success after 3 months
      follow-up with antisecretory treatment was 107/271 (39.5%) and with a prokinetic
      agent 122/282 (43.3%); the risk difference was 3.8% (95% CI -4.4% to 12.0%); the
      difference in symptom severity score after 4 weeks of treatment was 0.3; 95% CI 
      0.4% to 1.0%. For patients responding to 4 weeks of treatment, relapse-free time
      was 86 days in the prokinetic group and 79 days in the acid suppression group (P
      = 0.005). CONCLUSIONS: Antisecretory and prokinetic therapies are equally
      effective in primary care patients with uninvestigated dyspeptic complaints,
      though relapse rates are lower in patients treated with prokinetic treatment.

PMID- 11521985
TI  - Effects of the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester
      (L-NAME) on antropyloroduodenal motility and appetite in response to
      intraduodenal lipid infusion in humans.
AB  - BACKGROUND: Studies in animals indicate that endogenous nitric oxide (NO) is an
      important inhibitory neurotransmitter in the gastrointestinal tract and that it
      modulates food intake. We evaluate the role of NO mechanisms in mediating the
      effects of small intestinal nutrients on antropyloroduodenal motility and
      appetite in humans. METHODS: On 2 separate days, 8 healthy adult men received
      intravenous L-NAME 180 microg/kg/h or 0.9% saline (0-150 min); between 30 min and
      120 min, an intraduodenal lipid infusion (2 kcal/min) was administered, and at
      120 min subjects were offered a buffet meal (120-150 min). Antropyloroduodenal
      pressures were measured with a sleeve/sidehole manometric assembly. During the
      infusions, perceptions of hunger and fullness were assessed with visual analog
      questionnaires and amount and macronutrient content of food consumed at the
      buffet meal were quantified. Blood pressure and heart rate were monitored at
      regular intervals. RESULTS: Intraduodenal lipid infusion was associated with
      increases in fullness (P < 0.05) and in frequency of isolated pyloric pressure
      waves (P < 0.05) and basal pyloric pressure (P < 0.05); and decreases in hunger
      (P < 0.05) and in frequency of antral (P < 0.05) and duodenal (P < 0.05) pressure
      waves. L-NAME increased diastolic blood pressure (P = 0.08) and decreased heart
      rate (P < 0.05), but had no effect on antropyloroduodenal pressures or food
      intake. CONCLUSIONS: Intravenous administration of the systemic NO synthase
      inhibitor, L-NAME, in a dose that affects cardiovascular function in healthy
      humans does not modify the antropyloroduodenal motor and appetite responses to
      intraduodenal lipid infusion.

PMID- 11521986
TI  - Endomysial and tissue transglutaminase antibodies in coeliac sera: a comparison
      not influenced by previous serological testing.
AB  - BACKGROUND: Since transglutaminase was shown to be the antigen of endomysial
      antibodies (EMA), it has become possible to screen for coeliac disease (CD) with
      an enzyme-linked immunosorbent assay (ELISA) for transglutaminase antibodies
      (TTA). However, it is possible that sera used to show that TTA are found in CD
      were obtained from patients diagnosed because they were positive for EMA. So, a
      comparison between EMA and TTA has not been possible so far. METHODS: EMA and TTA
      were tested in sera from 52 controls and 56 untreated CD patients, who had not
      undergone serological testing. Samples were tested for TTA with an ELISA kit.
      Based on the ROC analysis of a pilot study, results were considered as either
      positive, borderline, or negative. EMA were analysed by indirect
      immunofluorescence on monkey oesophagus. RESULTS: Forty-nine CD patients were
      positive for TTA, six borderline, one negative. Forty-four controls were
      negative, seven borderline, one positive. If we consider borderline results to be
      positive, sensitivity is 98.2% and specificity 84.6%. EMA were positive in 53 CD
      patients; the controls were all negative. Performing TTA in all cases and EMA
      only in the few TTA borderline cases (12.0%) would have a sensitivity of 94.6%
      and a specificity of 98.1%. CONCLUSIONS: This study is the first to compare TTA
      with EMA. Due to 100% specificity and high sensitivity, EMA seems to be the most
      accurate coeliac antibody. Conversely, TTA offer advantages in terms of
      sensitivity and simplicity. A satisfactory strategy is to use TTA first and then
      EMA to confirm the borderline results.

PMID- 11521987
TI  - Familial occurrence of microscopic colitis: a report on five families.
AB  - BACKGROUND: The etiology and pathogenesis of microscopic colitis is unknown.
      Whether genetic predisposition is of importance, as in many other
      gastrointestinal diseases, is unknown. Familial occurrence of collagenous colitis
      has earlier been reported only in two families. METHODS: Familial occurrence of
      microscopic colitis was searched for in a Swedish national microscopic colitis
      register. RESULTS: Familial occurrence of microscopic colitis was identified in
      five families. In all families a sister-sister relationship was found. Two
      sisters with collagenous colitis had been living apart in different Nordic
      countries for many years before developing the disease. In one pair, the smoking
      sister had collagenous colitis and the never smoking sister had lymphocytic
      colitis. CONCLUSIONS: Considering the relative rarity of microscopic colitis,
      these findings indicate that a genetic predisposition may be of importance.

PMID- 11521988
TI  - Corticosteroids impair intestinal epithelial wound repair mechanisms in vitro.
AB  - BACKGROUND: Despite enormous progress in the medical treatment of inflammatory
      bowel diseases (IBD), corticosteroids still represent the most effective drugs in
      the management of acute IBD. Unfortunately, surgical intervention under
      concomitant therapy with corticosteroids is often complicated by impaired
      intestinal wound healing. Our aim was to assess the effects of the
      corticosteroids prednisolone and budesonide on different aspects of intestinal
      epithelial wound healing in vitro to identify potential causes for impaired
      intestinal wound healing under corticosteroid therapy. METHODS: The effects of
      both corticosteroids on intestinal epithelial cell function were studied in non
      transformed small intestinal epithelial intestinal epithelial cell line IEC-6
      cells and human colon cancer-derived HT-29 cells. Effects on epithelial migration
      were assessed using an in vitro wounding model. Effects on epithelial cell
      proliferation were assessed using colorimetric 3(4,5-dimethylthiazolyl-2)-2,5
      diphenyl tetrazolium bromide (MTT) assays. Transforming Growth Factor beta
      (TGFbeta) mRNA and protein expression were determined by semi-quantitative RT-PCR
      and ELISA. RESULTS: Prednisolone and budesonide caused a significant dose
      dependent inhibition of intestinal epithelial cell migration and proliferation in
      IEC-6 and HT-29 cells. Both corticosteroids induced apoptosis of intestinal
      epithelial cells in a dose-dependent fashion. Neither corticosteroid modulated
      the expression of TGFbeta mRNA and the synthesis of TGFbeta peptide. However,
      both corticosteroids stimulated the bioactivation of latent TGFbeta peptide.
      CONCLUSIONS: Prednisolone and budesonide inhibit intestinal epithelial cell
      restitution and proliferation in vitro. Both processes play a key role in the
      rapid resealing of the mucosal barrier following intestinal injury. Thus,
      impaired intestinal epithelial wound healing under corticosteroid therapy in vivo
      may be caused by inhibition of intestinal epithelial cell restitution and
      proliferation.

PMID- 11521989
TI  - A prospective randomized controlled trial of intravenous ciprofloxacin as an
      adjunct to corticosteroids in acute, severe ulcerative colitis.
AB  - BACKGROUND: The role of antibiotics in the treatment of ulcerative colitis is
      controversial. This study aims at assessing the therapeutic role of ciprofloxacin
      as an adjunct to corticosteroids in acute severe ulcerative colitis. METHODS: In
      this prospective, randomized, double-blind, placebo-controlled trial, 55
      consecutive patients fulfilling the criteria of Truelove and Witts for severe
      ulcerative colitis were randomized on admission to the hospital to receive
      intravenously ciprofloxacin (400 mg b.i.d.) (n = 29) or placebo (n = 27). All
      patients received parenteral nutrition, intravenous hydrocortisone (100 mg
      q.i.d.) and hydrocortisone enemas (100 mg b.i.d.). Patients were assessed after
      10 days of continuous treatment, or at any time a severe complication occurred.
      RESULTS: At study entry, there were no significant differences between treatment
      groups in any patient or disease-related parameter. Twenty-three of 29 patients
      (79.3%) treated with ciprofloxacin and 20 of 26 patients (77%) treated with
      placebo showed substantial improvement and were given oral steroids (P > 0.1).
      Six patients in each group did not improve (n = 10) or developed complications (n
      = 2). Nine of these 12 patients underwent emergency colectomy; three patients
      consented to receive intravenous cyclosporin but did not achieve remission of
      colitis and they underwent elective colectomy. There were no perioperative or
      late deaths. CONCLUSIONS: A short course of intravenous ciprofloxacin does not
      seem to augment the effect of corticosteroids for patients with acute, severe
      ulcerative colitis.

PMID- 11521990
TI  - p21/waf1/cip1 in gastric cancer: associations with histopathological subtypes,
      lymphonodal metastasis, prognosis and p53 status.
AB  - BACKGROUND: Cyclins and cyclin-dependent kinases are determining factors of the
      cell cycle. In the present study, we investigated the role of p21 and p53 in the
      biology of gastric cancer, focusing on its influence on progression and prognosis
      (n = 195). METHODS: P21 and p53 immunoreactivity was analysed
      immunohistochemically, applying monoclonal antibodies. The p53 status was
      comparatively evaluated by PCR-SSCP analysis of p53 mutations in selected
      tumours. RESULTS: Fifty-eight percent of the carcinomas were p21+ in more than 5%
      of the cancer cell nuclei, whereas 19% exhibited a p21 immunoreactivity in more
      than 20% of the nuclei. On the other hand, p53 was over-expressed (in more than
      50% of the nuclei) in about 45% of the specimens. P21 immunoreactivity in more
      than 5% of the nuclei was inversely related to the pN as well as pTNM cancer
      stage, whereas only a strong p21 expression (in >20% of the nuclei) was
      correlated with a better survival probability in a univariate analysis. The p53
      status was associated with lymphonodal metastasis, but not with prognostic data.
      In multivariate survival analyses, neither p21 nor p53 emerged as independent
      prognostic factors. Compared with the results of p53 mutation analysis by PCR
      SSCP. p21 immunoreactivity was reduced in p53-mutated cases. CONCLUSIONS: These
      features show an association of p21 over-expression with certain clinico
      pathological parameters of gastric cancer. In this context, our data suggest that
      p21 immunoreactivity in more than 5% of the tumour cells has a predictive value
      for the course of adenocarcinoma of the stomach.

PMID- 11521991
TI  - Effect of chronic administration of tauro-hyodeoxycholic acid on biliary bile
      acid composition and on biliary lipid secretion in humans.
AB  - BACKGROUND: Tauro-hyodeoxycholic acid is a hydrophilic bile acid of potential
      interest for treating cholestatic liver diseases. Bile acid pool is enriched with
      this bile acid during acute administration in patients with interrupted
      enterohepatic circulation. The aim of our study was to check the effect of
      chronic administration of tauro-hyodeoxycholic acid on biliary lipid composition
      and secretion in man with intact enterohepatic circulation. METHODS: We studied 7
      dyspeptic patients before and during taurohyodeoxycholic acid 750 mg/day given
      for 6-8 weeks. We measured bile acid composition in duodenal aspirate, and
      biliary lipid secretion was also measured in 5 of these patients using a duodenal
      perfusion technique. RESULT: Tauro-hyodeoxycholic was undetectable in duodenal
      aspirate in all patients before treatment, and was 2%, 4%, 5%, 7%, 7%, 8% and 13%
      of biliary bile acid during treatment in individual patients. The proportion of
      cholic, deoxycholic, chenodeoxycholic ursodeoxycholic and lithocholic acid was
      similar before and during treatment. Bile acid duodenal output remained unchanged
      during taurohyodeoxycholic by comparison with pretreatment with median difference
      -0.3 mmol (95% confidence interval 1.6 mmol). The corresponding difference for
      duodenal cholesterol and phospholipid output was 0.1 mmol (0.2 mmol) and 0.2 mmol
      (0.6 mmol). CONCLUSIONS: By contrast with acute administration in patients with
      interrupted enterohepatic circulation, chronic administration of tauro
      hyodeoxycholic to man with intact enterohepatic circulation has little effect on
      biliary lipid composition and secretion.

PMID- 11521992
TI  - TT virus infection in patients with primary hypogammaglobulinaemia: natural
      history and relationship to liver disease in the immunocompromised host.
AB  - BACKGROUND: TT virus (TTV) is a recently discovered human DNA virus with
      worldwide distribution, but with no clear disease association. The possibility of
      an enhanced TTV virulence in patients with immunodeficiencies has not yet been
      investigated but is of particular interest because other viruses have been
      demonstrated to cause severe and rapid liver disease in such patients. Here we
      analysed the characteristics of TTV infection in a large cohort of patients with
      primary hypogammaglobulinaemia (PHG) and whether TTV has a role in the frequently
      observed cryptogenic liver disease in these patients. METHODS: 83 Norwegian
      patients with PHG (serum immunoglobulin G < 2 g/L), receiving substitution
      treatment with immunoglobulins, were followed regularly for median 10.2 years
      (range 2-30). TTV DNA was sought in serum samples and three immunoglobulin
      preparations by polymerase chain reaction; TTV DNA quantitation, DNA sequencing
      and phylogenetic analysis were performed in selected samples. RESULTS: TTV DNA
      was detected in 27 of 83 (32.5%) patients and was not associated with a
      particular type of PHG. The prevalence of TTV infection was dependent on
      intravenous immunoglobulin administration, duration of therapy and patient's age.
      TTV DNA was found in two of three currently used immunoglobulin preparations. In
      the longitudinal study, whether TTV was cleared or newly acquired had no impact
      on liver function tests and no particular TTV strain was found in patients with
      more severe liver disease. CONCLUSIONS: TTV infection is common in patients with
      PHG. Treatment with immunoglobulins has a role in the transmission of TTV in
      these patients. However, we found no evidence of TTV-induced liver disease in
      this group of immunocompromised patients.

PMID- 11521993
TI  - Periampullary diverticula cause pancreatobiliary reflux.
AB  - BACKGROUND: Periampullary diverticula are associated with dysfunction of the
      sphincter of Oddi. Papillary dysfunction may allow reflux of pancreatic juice as
      well as intestinal contents into the common bile duct. We prospectively
      investigated pancreatobiliary reflux in patients with and without periampullary
      diverticula. METHODS: The ductal bile was sampled for amylase concentration
      during endoscopic retrograde cholangiopancreatography in 47 patients with
      choledocholithiasis (n = 29; with (n = 14) or without (n = 15) periampullary
      diverticula) or gallbladder cholesterol polyps (n = 18; with (n = 6) or without
      (n = 12) diverticula). RESULTS: The amylase concentration within the ductal bile
      was significantly higher in choledocholithiasis patients with periampullary
      diverticula (1621 +/- 587 IU/l) than in those without diverticula (1155 +/- 418
      IU/l). The amylase concentration tended to be higher in gallbladder polyp
      patients with diverticula (1087 +/- 275 IU/l) than in those without diverticula
      (833 +/- 272 IU/l). Irrespective of the presence or absence of diverticula,
      patients with bile duct stones had significantly higher amylase concentrations
      than those with gallbladder polyps. CONCLUSIONS: Periampullary diverticula cause
      pancreatobiliary reflux. Further investigation is required to determine the
      clinical implication of pancreatobiliary reflux.

PMID- 11521994
TI  - Increased turnover of Gc-globulin in patients with hepatic encephalopathy.
AB  - BACKGROUND: A low serum level (< 100 mg/L) of the actin-scavenger Gc-globulin is
      a prognostic marker of non-survival in fulminant hepatic failure (FHF). It is
      unknown whether decreased production or increased consumption (or both) is
      responsible for the low Gc-globulin levels. METHODS: Ten patients with FHF and
      four patients with acute or chronic liver disease (AOCLD) with hepatic
      encephalopathy (HE) grades II-IV were included. Eight patients with cirrhosis
      (chronic liver disease, CLD) without HE served as controls. Total, free, and
      actin-bound Gc-globulin were measured in samples from an artery, a central vein,
      and a hepatic vein. In 12 patients (9 FHF, 3 AOCLD), concentrations were measured
      before and after high volume plasmapheresis (HVP). RESULTS: Total Gc-globulin was
      reduced to 21%, 40%, and 43% of the normal level in the FHF, AOCLD, and CLD
      groups, respectively, whereas bound Gc-globulin was within normal range in all
      patients. The Gc:actin complex ratio was increased 3.8, 2.5, and 1.9-fold
      compared with normal levels. Total, free, and bound serum Gc-globulin levels did
      not differ among arterial, systemic venous, or hepatic venous blood. Total Gc
      globulin rose to >100 mg/L in all patients after HVP, whereas bound Gc-globulin
      remained unchanged. The Gc-globulin production rate in FHF and AOCLD patients was
      increased to 4.1 +/- 1.3 mg/min compared to literature values of 0.6 mg/min in
      healthy individuals. The estimated half-life of total Gc-globulin was shorter in
      the patients compared to healthy individuals (127 +/- 56 min and 870 min,
      respectively). CONCLUSIONS: Gc-globulin levels were reduced in patients with FHF
      and AOCLD because a 7-fold increase of Gc-globulin production rate could not
      compensate for the accelerated clearance. Bound Gc-globulin was maintained within
      normal levels in all circumstances studied, indicating a possible regulatory role
      of this parameter in the clearance of actin.

PMID- 11521995
TI  - Taking the hype out of hyperfibrinogenaemia?

PMID- 11521996
TI  - A novel transgenic mouse model of hyperfibrinogenemia.
AB  - Hyperfibrinogenemia is a risk predictor in several diseases, including
      cardiovascular disease. Nevertheless, it remains unknown whether elevated
      fibrinogen has an etiologic role in or is a reflection of disease pathogenesis,
      or both. To examine this question, we generated a mouse model of
      hyperfibrinogenemia. We isolated the mouse fibrinogen locus, containing the three
      fibrinogen genes, in a single P1 clone. This approximately 100 kb clone was
      injected into C57Bl/6J zygotes. Three transgenic lines were identified, two with
      elevated fibrinogen, 1.4- and 1.7-fold relative to normal. We characterized the
      line with the higher level. Northern blots of total RNA showed transgene
      expression was liver specific, and the message levels were 2- to 3-fold enhanced.
      Fibrinogen in transgenic mice was normal in both immunologic and clotting assays.
      Our data indicate that over-expression of all three fibrinogen genes is necessary
      to achieve hyperfibrinogenemia. We saw no increase in mortality or morbidity, no
      gross abnormalities in the organs, and no histologic differences in lung, liver,
      spleen or kidney, in transgenic mice relative to normal littermates. We conclude
      that elevated fibrinogen did not cause disease in mice. We anticipate that
      breeding these mice to other mouse models of disease will demonstrate whether
      hyperfibrinogenemia has a role in the initiation or progression of symptomatic
      disease.

PMID- 11521997
TI  - Moderate wine and alcohol consumption: beneficial effects on cardiovascular
      disease.

PMID- 11521998
TI  - Diagnostic accuracy of compression ultrasonography for the detection of
      asymptomatic deep venous thrombosis in medical patients--the TADEUS project.
AB  - We assessed the accuracy of venous compression ultrasonography (CUS) for the
      detection of asymptomatic deep vein thrombosis in 122 consecutive patients, with
      a mean age of 69 years, who were hospitalised in an internal medicine unit. All
      included patients had CUS within 48 h of admission. Twelve out of 17 patients
      with a positive CUS underwent phlebography, as the others withdrew their consent,
      whereas the remaining 105 patients with a negative serial CUS testing were
      clinically followed-up at 3 months. We found that CUS had a sensitivity and a
      specificity of respectively 1 (95% CI, 0.73 to 1) and 1 (95% CI, 0.96 to 1) for
      the detection of asymptomatic deep vein thrombosis. Kappa-coefficients for intra
      observer and inter-observer agreements were respectively 0.88 and 0.56. We
      concluded that venous compression ultrasonography, performed as described,
      fulfils requirements of a screening test that could be available for prophylactic
      clinical trials or epidemiological researches.

PMID- 11521999
TI  - The value of ultrasound screening for proximal vein thrombosis after total hip
      arthroplasty--a prospective cohort study.
AB  - The role of ultrasound screening for proximal deep-vein thrombosis (DVT)
      following major hip surgery is controversial. 202 consecutive patients, who had
      received warfarin prophylaxis after total hip arthroplasty underwent a bilateral
      ultrasound assessment of the proximal vein system (using the criterion of vein
      compressibility) before hospital discharge. In the 9 patients (4.5%; 95% CI, 2.1
      8.3%) with positive test anticoagulant treatment was successfully continued for
      three months. In all the remaining 193 patients the warfarin treatment was
      withdrawn. A second ultrasound test was performed 15 days later, and showed a new
      (asymptomatic) abnormality compatible with proximal DVT in 2 patients (1.0%; 95%
      CI, 0.1-3.7%). All other 191 patients remained asymptomatic until the completion
      of a 3-month follow-up period (rate of symptomatic thromboembolism, 0/191, 0%;
      95% CI, 0-1.9%). Because of the relatively high incidence of proximal DVT in
      patients undergoing major orthopaedic surgery under warfarin prophylaxis,
      screening for proximal DVT at hospital discharge in these patients is indicated.
      The negativity of this test has the potential of safely preventing the extension
      of anticoagulation beyond hospital stay. A larger controlled study in which the
      value of this strategy is tested against the prolongation of oral anticoagulation
      in patients with a negative ultrasound screening at discharge is indicated.

PMID- 11522000
TI  - A cross sectional study of antiphospholipid-protein antibodies in patients with
      venous thromboembolism.
AB  - OBJECTIVE: To look for an association between venous thromboembolism (VTE) and
      antiphospholipid antibodies (aPL) in patients without Systemic Lupus
      Erythematosus (SLE) when implementing, beside conventional assays, new tests for
      aPL screening directed towards purified proteic targets. METHODS: We conducted a
      cross-sectional, hospital-based study of consecutive unselected outpatients. We
      compared VTE+ patients to VTE- among 398 consecutive unselected outpatients
      referred for clinical suspicion of VTE. To detect aPL, the following ELISAs were
      performed: 1) a conventional standardized ELISA 2) an improved APA assay, 3) an
      anti-Beta2GPI ELISA, 4) an anti-Annexin V ELISA, 5) an anti-Prothrombin ELISA. We
      sought an association between VTE and aPL through a quantitative (t-test) and a
      qualitative comparison (chi-square test, according to the cut-off values set as
      the 95th percentile of aPL distribution). First we conducted an analysis of all
      patients. Then we stratified them into 2 subgroups, with or without a wellknown
      risk factor for VTE (prolonged immobilization >72h, surgery or trauma within the
      past three months, current malignancy). RESULTS: 61% of patients were classified
      as VTE-positive. Before stratification, we did not find any significant
      association between the VTE status and aPL. However, after stratification, in the
      subgroup without risk factors for VTE, the frequency of positive values as
      regards the anti Prothrombin antibodies detection was significantly higher in
      VTE+ patients (p = 0,04). CONCLUSION: The presence of anti Prothrombin antibodies
      might be an independent risk factor of VTE. However systematic screening for aPL
      in non SLE patients referred for VTE suspicion at the time of the thrombo-embolic
      event has little clinical relevance.

PMID- 11522001
TI  - Early inhibition of activated fibrinolysis predicts microbial infection, shock
      and mortality in febrile medical patients.
AB  - To evaluate the contribution of an imbalance between coagulation activation and
      fibinolysis activation and inhibition to morbidity and mortality in sepsis, we
      determined in medical hospitalized patients at inclusion (day 0) for fever
      (temperature above 38.0 degrees C axillary or 38.3 degrees C rectally), and daily
      thereafter for two days, circulating thrombin-antithrombin III (TAT) complexes,
      plasmin-alpha2-antiplasmin (PAP) complexes (day 0 only), tissue-type plasminogen
      activator (t-PA), plasminogen activator inhibitor-1 (PAI-1) and interleukin (IL)
      6, the latter as a marker of the inflammatory host response. Study variables were
      1) positive microbiological results for specimens from local sites associated
      with a clinical infection, positive blood cultures (including parasitemia) or
      both, within 7 days after inclusion, 2) development of shock, i.e. systolic blood
      pressure <90 mmHg or a reduction of 40 mmHg from baseline within 7 days after
      inclusion, and 3) death related to febrile illness within 28 days after
      inclusion. The peak plasma levels of TAT complexes were elevated in 44% and the
      PAP complexes in all patients. The t-PA and PAI-1 levels were elevated in 74 and
      94% of patients, respectively. Values for TAT and PAP did not differ among
      subgroups, while peak t-PA and IL-6 levels were higher in patients with positive
      microbiological results, developing shock or ultimately dying than in those
      without the complications (p<0.005). Peak PAI-1 levels were elevated in patients
      developing shock and ultimate death versus those with an uncomplicated course (p
      <0.05). Peak IL-6 related to PAI-1 and t-PA levels, which interrelated. Patients
      with elevated TAT levels had increased plasma levels of IL-6, PAP, PAI-1 and t-PA
      versus those with normal TAT (p <0.05). Our data indicate that inhibition of
      activated fibrinolysis, which may partly depend on both cytokinemia and
      activation of coagulation, predicts microbial infection, septic shock and
      mortality of febrile medical patients. This suggests an early pathogenic role of
      inhibition of activated fibrinolysis in the downhill course of serious microbial
      infection.

PMID- 11522002
TI  - Different effects of oral and transdermal hormone replacement therapies on factor
      IX, APC resistance, t-PA, PAI and C-reactive protein--a cross-sectional
      population survey.
AB  - The effects of hormone replacement therapy (HRT) on thrombosis risk, thrombotic
      variables, and the inflammatory marker C-reactive protein (CRP) may vary by route
      of administration (oral versus transdermal). We studied the relationships of 14
      thrombotic variables (previously related to cardiovascular risk) and CRP to
      menopausal status and to use of HRT subtypes in a cross-sectional study of 975
      women aged 40-59 years. Our study confirmed previously-reported associations
      between thrombotic variables and menopausal status. Oral HRT use was associated
      with increased plasma levels of Factor IX, activated protein C (APC) resistance,
      and CRP; and with decreased levels of tissue plasminogen activator (t-PA) antigen
      and plasminogen activator inhibitor (PAI) activity. Factor VII levels were higher
      in women taking unopposed oral oestrogen HRT. The foregoing associations were not
      observed in users of transdermal HRT; hence they may be consequences of the
      "first-pass" effect of oral oestrogens on hepatic protein synthesis. We conclude
      that different effects of oral and transdermal HRT on thrombotic and inflammatory
      variables may be relevant to their relative thrombotic risk; and suggest that
      this hypothesis should be tested in prospective, randomised studies.

PMID- 11522003
TI  - Impairment of the plasmin activation system in primary pulmonary hypertension:
      evidence for gender differences.
AB  - Primary pulmonary hypertension (PPH) is a rare disorder, with marked in-situ
      thrombosis of small pulmonary vessels occurring primarily in adult women. We
      investigated whether differences in the plasmin- and thrombin activation system
      are associated with the predominate affection of females. Plasma levels of
      plasminogen activator inhibitor type 1 (PAI-1), tissue-type plasminogen activator
      (t-PA), fibrinogen, thrombin-antithrombin (TAT) complexes, and prothrombin
      fragments (F1.2) were measured at baseline and after standardized venous
      occlusion (VO) in patients with PPH (24 female, 9 male). At baseline, females
      showed significant higher TAT levels (p = 0.05), higher t-PA antigen levels (p =
      0.01) and higher fibrinogen levels (p = 0.03) with positive correlation to mean
      pulmonary artery pressure (mPAP), as well as nonsignificant lower t-PA activity,
      higher PAI-1 antigen and activity and F1.2 levels. After VO, females showed a
      significantly blunted increase in t-PA antigen (p = 0.01) and t-PA activity (p =
      0.001), correlating with mPAP, as well as increased PAI-1 activity (p = 0.05). We
      hypothesize, that the observed presence of gender differences in the plasmin- and
      thrombin activation system in PPH leading to an antifibrinolytic/prothrombotic
      state might, in part, explain the female predominant incidence of this disease.

PMID- 11522004
TI  - Hospitalisation for upper gastrointestinal bleeding associated with use of oral
      anticoagulants.
AB  - The incidence of hospitalisation for upper GI bleeding with use of oral
      anticoagulants (OA) alone or in combination with other drugs was examined in a
      cohort of 4,204 users of OA, identified through record linkage between a
      population-based prescription database and a hospital discharge registry in
      Denmark, and compared with the incidence in the general population not exposed to
      OA. The standardised incidence ratio (SIR) was 2.8 (95% CI = 1.6-4.5) for use of
      OA alone. SIRs tended to be higher for use of OA combined with acetaminophen
      alone (4.4, 95% CI = 1.2-11.4), non-aspirin NSAIDs alone (8.0, 95% CI = 2.1 to
      20.4) or aspirin/corticosteroids alone (3.8, 95% CI = 0.8-11.0), respectively.
      These results indicate that use of OA is associated with a significantly
      increased risk of upper GI bleeding, with still higher risks associated with the
      concomitant use of other medications including acetaminophen. Further research is
      needed to clarify the extent to which drugs interacting with oral anticoagulants
      may cause GI bleeding and the mechanisms through which these associations
      operate.

PMID- 11522005
TI  - Characteristics of anticoagulant therapy and comorbidity related to
      overanticoagulation.
AB  - The risk of hemorrhage when using coumarin anticoagulants sharply increases when
      the International Normalised Ratio (INR) is > or =6.0. We performed a prospective
      cohort study with a nested case-control design among 17,056 outpatients of an
      anticoagulation clinic to determine the incidence of overanticoagulation and to
      study the association between overanticoagulation and characteristics of
      anticoagulant therapy and comorbidity. The incidence rate of an INR > or =6.0 was
      7.8 per 10,000 treatment days in prevalent users on the starting date and 22.5
      per 10,000 treatment days in incident users during the study period. 300 cases
      with an INR > or =6.0 were compared with 302 randomly selected matched controls
      with an INR within the target zone. Patients on acenocoumarol had an increased
      risk of an INR > or =6.0 compared to patients on phenprocoumon. Regarding
      comorbidity, impaired liver function, congestive heart failure, diarrhea and
      fever were risk factors for overanticoagulation. Increased monitoring of INR
      values if risk factors are present or avoidance of risk factors could prevent
      excess anticoagulation and potential bleeding complications.

PMID- 11522006
TI  - Anticardiolipin antibody assay: a methodological analysis for a better consensus
      in routine determinations--a cooperative project of the European Antiphospholipid
      Forum.
AB  - Despite the widely recognized practical importance of anticardiolipin (aCL)
      ELISA, the reliability of this test has been recently discussed. In order to
      investigate this area on European scale, we sent to 30 experienced centers a
      questionnaire focusing on the diagnostic procedures applied to patients with
      antiphospholipid syndrome (APS) and on the detailed protocols used to perform
      aCL. Anticardiolipin ELISA was found to be the most frequently performed test in
      patients with suspected APS, but significant difference was shown among the
      various protocols. The cross-laboratory multiple examination of ten serum samples
      evaluated independently by the 24 centers pointed out the difficulty in getting
      comparable results. Therefore a "consensus" protocol was derived from the aCL
      methods giving the best performance. The materials and reagents necessary to
      perform the "consensus" method, including, as putative standards, one IgG and one
      IgM monoclonal antibody (HCAL and EY2C9) were distributed to 19 Centers. The
      results of one IgG and one IgM aCL high positive sera measured in serial
      dilutions were compared. A progressive decrease in the variability of the values
      obtained for a given sample appeared evident when all the laboratories used the
      same standard, in their own in-house ELISA and even more in the "consensus"
      ELISA. Our data show that aCL ELISA standardization is necessary in order to
      obtain comparable results in different laboratories.

PMID- 11522007
TI  - Quantification of lupus anticoagulants in clinical samples using anti-beta2GP1
      and anti-prothrombin monoclonal antibodies.
AB  - Quantification of lupus anticoagulant (LA) in clinical samples is hampered by the
      lack of a suitable standard of activity. We evaluated the use of mAbs displaying
      LA activity for this purpose. As most patient samples contain both
      beta2Glycoprotein I (beta2GP1) and prothrombin dependent LA, a combination of two
      mAbs, one of each specificity, was added to normal plasma in a concentration from
      0 to 60 microg/ml. Eight assay systems using different reagents and instruments
      were used. The calibration curves were linear for all but one, with marked
      differences between the responsiveness to each mAb. A panel of plasmas from 69
      patients with persistent LA diagnosed using the SSC-ISTH criteria was tested. An
      antiphospholipid syndrome (APS) was present in 40, whereas 29 were asymptomatic.
      LA activities of individual plasmas varied between assays (p < 10(-4)), but
      homogeneous subgroups were identified. In a majority of samples, LA activity
      displayed a prothrombin-dependent profile, with a variable contribution of
      beta2GP1-dependent activity. The latter was associated to beta2GP1 antibodies
      detected by solid-phase immunoassay. By using 3 dilute Russell viper venom time
      assays, higher LA titers were found in APS, compared to asymptomatic patients (p
      <0.05).

PMID- 11522008
TI  - Beta2-glycoprotein I-dependent anticardiolipin antibodies preferentially bind the
      amino terminal domain of beta2-glycoprotein I.
AB  - Many of the autoantibodies in antiphospholipid syndrome (APS) are directed
      against beta2-glycoprotein I (beta2-GPI). Recent studies from our laboratories
      have indicated that the immunodominant binding epitope(s) for high titer,
      affinity purified antibodies from 11 APS patients are localized to the amino
      terminal domain (domain 1) of beta2-GPI. The present study employed surface
      plasmon resonance to localize the immunodominant domain in serum samples from a
      large cohort of patients with GPL values ranging from 21 to 230 units (n = 106
      patients). Eighty-eight percent of patients showed > or = threefold selectivity
      for beta2-GPI containing domain 1 relative to the domain deletion mutant that
      lacked domain 1. The domain 1 binding activity in patient serum was abolished by
      removing the IgG fraction from the serum and the binding activity could be fully
      reconstituted with the IgG fraction. Thus, analysis of serum samples from a large
      cohort of APS patients indicates that the immunodominant binding epitope(s) for
      anti-beta2 antibodies are localized to the amino terminal domain of beta2-GPI.

PMID- 11522009
TI  - A factor VIII minigene comprising the truncated intron I of factor IX highly
      improves the in vitro production of factor VIII.
AB  - The biosynthesis of coagulation factor VIII (FVIII) is hampered by successive
      controls that limit its production. To improve this production, a truncated
      intron I sequence of factor IX (TFIXI1) was inserted in FVIII cDNA in place of
      FVIII introns 1, 12 and 13 and also as a combination between introns 1 and 12,
      and introns 1 and 13. The intron 12 and 13 locations were targeted because this
      region was previously shown to contain a transcriptional silencer. The expression
      of FVIII in CHO and HepG2 cells revealed important variations in the properties
      of the minigenes depending on the TFIXI1 insertion sites. In FVIII intron 13
      location the TFIXI1 seemed to diminish the transcriptional silencer activity,
      whereas it was poorly spliced in intron 12 position. Among the five constructs,
      FVIII I1+13 leaded to a significant improvement in FVIII secretion (13 times)
      that was associated with a dramatic intracellular accumulation in cells.
      Therefore, the FVIII I1+13 minigene could represent a particular interest to
      produce recombinant FVIII in vitro as well as in the aim of gene therapy of
      haemophilia A.

PMID- 11522010
TI  - A sensitive immunochemical assay for measuring the concentration of the activated
      protein C-protein C inhibitor complex in plasma: use of a catcher antibody
      specific for the complexed/cleaved form of the inhibitor.
AB  - Activated protein C (APC) is a serine proteinase that regulates blood
      coagulation. In plasma it is inhibited mainly by the protein C inhibitor (PCI).
      The plasma concentrations of APC-PCI complex is increased in hypercoagulative
      states such as deep venous thrombosis. Formation of the APC-PCI complex induces a
      drastic conformational change in PCI that exposes new epitopes (neoepitopes) on
      the molecule. We have devised a simple immunofluorometric sandwich assay for
      measurements of the concentrations of APC-PCI complex, employing as the catcher,
      a monoclonal antibody that has a high affinity (K(D) = 4 x 10(-11) M) for a
      complexation-specific neoepitope that is expressed on PCI. A monoclonal antibody
      against protein C is employed as the tracer. The method gives a linear dose
      response curve (0.06-50 microg/l), has a low detection limit (0.06 microg/l) and
      no crossreactivity with native PCI at physiologic plasma concentrations. We have
      now determined the concentration of the APC-PCI complex in healthy individuals.

PMID- 11522011
TI  - Effect of melagatran on prothrombin time assays depends on the sensitivity of the
      thromboplastin and the final dilution of the plasma sample.
AB  - Prothrombin time (PT) assays are clotting methods that measure the activity of
      vitamin K-dependent coagulation factors (F) II, VII, and X. There are three main
      types of PT assays in general usage, namely the Quick assay, Owren's assay and PT
      dry chemistry test cards. PT assays were initially developed to monitor dose
      adjustments of vitamin K antagonists such as warfarin. The aim of the present
      study was to investigate whether commercially available PT assays are suitable
      for evaluating the anticoagulant activity of direct thrombin inhibitors.
      Melagatran, a reversible direct thrombin inhibitor, was added to human plasma at
      concentrations ranging from 0.1 to 2.0 micromol/l. Seventeen different
      commercially available PT kits were used, including thirteen Quick reagents, two
      Owren reagents and two PT test cards. The sensitivity of the different reagents,
      expressed as the concentration of melagatran that doubled the prothrombin time
      (IC50) varied widely, with Thromboplastin S and Thromboplastin HS being the most
      sensitive (IC50 = 0.9 micromol/l). The reagents with apparently the lowest
      sensitivity were the two Owren reagents Nycotest PT and SPA 50 with an IC50 of
      2.2 and 2.9 micromol/L, respectively. This is most likely due to a higher
      dilution of melagatran in these assays compared to the dilution in the Quick
      assays. The results were also dependent on the International Sensitivity Index
      (ISI) of each reagent. The concentration of melagatran that produced an
      International Normalized Ratio (INR) of 2 was calculated from dose-response
      curves for each assay, and these results revealed that reagents with a high ISI
      value gave an INR of 2 at much lower concentrations of melagatran (0.5-0.7
      micromol/L) than those with an ISI-values around one (0.9-1.2 micromol/L). It was
      found that INR depends not only on the plasma concentration of melagatran, but
      also on the sensitivity of the PT reagent and on the final dilution of the plasma
      sample in the prothrombin time assay. Thus, since the same melagatran
      concentration can be associated with widely varying PT/INR results depending on
      the specific assay used it is concluded that PT assays and INR can not be used to
      monitor melagatran activity.

PMID- 11522012
TI  - High affinity binding of heparin by necrotic tumour cells neutralises
      anticoagulant activity--implications for cancer related thromboembolism and
      heparin therapy.
AB  - We have observed a striking neutralisation of the anticoagulant activity of
      unfractionated heparin in the presence of a pancreatic carcinoma cell line (MIA
      PaCa-2) due to binding of around 9 microg of heparin per 10(7) cells (apparent
      Kd, 30 nM). The loss of anticoagulant activity was less marked in the presence of
      low molecular weight forms of heparin. Binding to the cell blocked acceleration
      of the thrombin:antithrombin interaction by heparin. Neutralisation of heparin
      activity was also shown to occur in the presence of a number of other tumour cell
      lines. FACS analysis demonstrated that live cells did not bind heparin and high
      affinity binding only occurred to dead MIA PaCa-2 cells. Heparin binding proteins
      accumulating in cell medium were identified as histone and ribosomal proteins
      that will become exposed during necrosis. The release of these proteins from
      cells within the necrotic core of a tumour or from cells killed during
      chemotherapy may abrogate the heparan sulphate/antithrombin system and possibly
      contribute to the idiopathic thromboembolism often associated with cancer
      (Trousseau's syndrome). The findings also suggest a reason for the reported
      advantage of LMWH over UFH in treating venous thromboembolism in cancer patients
      and in improving patient survival.

PMID- 11522014
TI  - Selection of phages that inhibit vWF interaction with collagen under both static
      and flow conditions.
AB  - Phages from a pentadecamer phage display library were selected for binding to vWF
      by affinity panning. Bound phages were selectively eluted with human collagen
      type I. After the third round of panning 95% of individual phage clones bound to
      vWF. The B8-phage inhibited the binding of collagen to vWF with an IC50 of 0.6 x
      10(10) phages/ml, and of vWF to collagen with an IC50 of 1.0 x 10(10) phages/ml
      at 0.5 microg/ml vWF. Under flow conditions, 1.5 x 10(11) B8-phage/ml nearly
      completely inhibited platelet deposition on a human collagen type I coated
      surface at a shear rate of 1200 s(-1), while phages without an insert had no
      effect. The peptide corresponding to the one displayed on the B8-phage competed
      with the phage for binding to vWF with an IC50 of 30 microg/ml (16 microM). The
      peptide furthermore inhibited vWF-binding to collagen with a maximum of 40% at a
      concentration of 1.25 mg/ml (650 microM), higher concentrations of peptide could
      not improve this. We thus have selected phages that are potent vWF-binders and
      that can be used as tools to detect vWF, to inhibit vWF-collagen interaction and
      to further analyse the role of vWF-collagen binding.

PMID- 11522013
TI  - Expression of protein S in the murine heart and cultured mouse cardiomyocytes is
      down-regulated by cytokines.
AB  - Protein S (PS), a co-factor of activated protein C, is a vitamin K-dependent
      anticoagulant protein and is known to be produced extrahepatically. In the
      present study, the concentration of PS mRNA was determined tissue by tissue in
      the mouse, and it was high in lung, adrenal and heart as well as in liver. We
      further investigated the effects of lipopolysaccharide (LPS), tumor necrosis
      factor-alpha (TNF-alpha), and interleukin-1 (IL-1) on the PS mRNA expression in
      murine tissues in vivo. Although LPS and TNF-alpha significantly decreased the
      expression level of PS mRNA in all tissues examined (e. g., lung, liver, heart,
      and kidney) and the PS antigen level in plasma, the suppressive effect of IL-1 on
      PS gene expression was limited to heart. More specifically, considerable amounts
      of PS mRNA and antigen were expressed in a cultured mouse cardiomyocyte cell
      line, and again, treatment with IL-1 decreased the PS expression in these cells.
      These observations raise a possibility that the expression of cardiac PS may
      contribute to the regional anticoagulant potential in heart, and suggest that the
      decreased PS expression by cytokines may result in an increase in the systemic
      and/or regional prothrombotic potential under inflammatory conditions.

PMID- 11522015
TI  - Fibrinolysis/proteolysis balance in stable angina pectoris in relation to
      angiographic findings.
AB  - The plasma fibrinolytic/proteolytic balance was assessed in 60 stable angina
      patients who underwent control coronary catheterization and the results were
      correlated with angiographic findings and control samples (n = 20). The
      concentrations of t-PA, PAI-1, collagenase (MMP-1), tissue inhibitor of MMP (TIMP
      1), plasmin-antiplasmin (PAP) complexes and alpha2-macroglobulin (alpha2-M) were
      measured in plasma samples. The results showed a significant increase of PAP (p
      <0.001) and a reduction of alpha2-M (p <0.001) in the group of patients when
      compared to controls, indicating a degree of fibrinolysis/proteolysis activation.
      There was no correlation between the different parameters analyzed and the extent
      of angiographically proven atherosclerosis (one or more stenotic vessels), while
      the t-PA levels were significantly elevated (p <0.03) in patients with coronary
      stenosis > or =75% or occlusion. We conclude that there is a disturbance of the
      plasma fibrinolysis/proteolysis in patients with stable angina not related to the
      extent of atherosclerosis. The t-PA levels may be a good marker for coronary
      occlusion in these patients.

PMID- 11522016
TI  - Enhanced fibrinolytic potential in mice with combined homozygous deficiency of
      alpha2-antiplasmin and PAI-1.
AB  - Alpha2-antiplasmin (alpha2-AP) and plasminogen activator inhibitor-1 (PAI-1) are
      the main physiological inhibitors of the plasminogen/plasmin system in mammalian
      plasma. In the present study, the relative importance of both inhibitors was
      evaluated with the use of mice with single or combined deficiency of alpha2-AP
      and PAI-1 in the same genetic background. Mice with combined deficiency (alpha2
      AP-/-:PAI-1-/-) are viable, develop normally and are fertile. After amputation of
      the tail, bleeding times are prolonged (>15 min) in alpha2-AP-/-: PAI-1-/- mice,
      as compared to double wild-type or single deficient mice (4.6 to 10 min).
      Spontaneous lysis after 4 h of intravenously injected 125I-fibrin labeled plasma
      clots is significantly higher in mice with alpha2-AP deficiency both in the PAI
      1+/+ background (89+/-2% versus 42+/-3%; p = 0.002) and in the PAI-1-/-
      background (83+/-4% versus 53+/-5%; p = 0.002). PAI-1 deletion in the alpha2
      AP+/+ or alpha2-AP-/- background, however, has no significant effect (p = 0.13 or
      0.18, respectively). Four hours after endotoxin injection, fibrin deposition in
      the kidneys is not significantly affected by PAI-1 deletion in mice with alpha2
      AP+/+ or alpha2-AP-/- background (p = 0.07 and 0.19, respectively). In contrast,
      alpha2-AP deletion causes significantly reduced fibrin deposition in the PAI-1+/+
      background (p = 0.01). Endotoxin injection causes a dramatic increase in PAI-1
      antigen levels in kidney extracts of PAI-1+/+ animals, without effect on alpha2
      AP levels. Taken together, these data indicate that the higher endogenous
      fibrinolytic capacity observed in mice with combined deficiency is mainly due to
      the lack of alpha2-AP and suggest a less important role for PAI-1.

PMID- 11522017
TI  - Plasma PAI-1 levels in obese children--effect of weight loss and influence of PAI
      1 promoter 4G/5G genotype.
AB  - An association between an increase in plasminogen activator inhibitor type 1 (PAI
      1) and obesity, and also between elevated levels of PAI-1 and the presence of PAI
      1 promoter 4G allele has been described in adults and can contribute to increased
      risk of cardiovascular disease. It has also been suggested that in adults a
      decrease in adiposity has beneficial effects on the haemostatic system. However,
      less information is available regarding adiposity and fibrinolysis in children.
      The aim of the present study is to evaluate the effect of weight loss and the
      influence of the PAI-1 promoter 4G/5G genotype on the fibrinolytic system and
      lipid parameters in obese children. The clinical groups included 102 obese
      children and 105 controls of similar age and sex distribution. A significant
      decrease in fibrinolytic activity due to a significant increase in PAI-1 antigen
      and activity levels was observed in the obese children in comparison with the
      control group. In obese children, no significant differences in PAI-1 levels
      between the PAI-1 4G/5G genotypes were obtained. A significant correlation was
      observed between PAI-1 antigenic and functional levels and body mass index (BMI),
      as well as between PAI-1 levels and both triglyceride and insulin levels. No
      correlation between PAI-1 levels and either cholesterol or glucose levels was
      observed. After a three-month period of treatment to reduce weight, an increase
      in fibrinolytic activity due to a decrease in PAI- levels was observed in the
      obese children who had reduced their BMI in comparison with the group of obese
      children who did not show a decrease in their BMI. No significant differences
      between the two groups with respect to the variations in tissue type plasminogen
      activator and fibrinogen levels were obtained after three months of intervention
      to reduce weight. A significant correlation was observed between variations in
      BMI and variations in PAI-1 levels, and a significant inverse correlation was
      also observed between previous PAI-1 levels and variation in PAI-1 levels.
      Therefore, the largest decrease in PAI-1 levels was observed in the obese
      children with the highest previous PAI-1 levels. In conclusion, a decrease in BMI
      in obese children shows a favourable effect on the fibrinolytic system due to a
      decrease in PAI-1 levels. However, no influence of 4G/5G genotype on PAI-1 levels
      was observed.

PMID- 11522018
TI  - Complementary roles for fibrin(ogen), thrombospondin and vWF in mediating shear
      dependent aggregation of platelets stimulated at threshold thrombin
      concentrations.
AB  - We have evaluated the relative contribution of the adhesive ligands, von
      Willebrand factor (vWF), fibrinogen (Fg) and thrombospondin (TSP), all surface
      expressed on washed platelets (WP) activated with a threshold thrombin
      concentration (approximately 0.04 U/ml), to platelet microaggregation (PA) at
      shear rates (G) from 300-2000 s(-1). In suspensions of thrombin-activated WP
      sheared immediately (tau0), all three ligands were required for optimal
      aggregation at all G, as shown by a 50-70% inhibition of capture efficiencies of
      PA (measured from initial rates of PA), by antibodies (Abs) directed against each
      protein. This aggregation involved both GPIb and GPIIbIIIa, as indicated by
      approximately 80% and 100% inhibition by Ab 6D1 and Ab 10E5, respectively. For WP
      preexposed to thrombin for 10 min to ensure maximal surface expression of
      secreted ligands and activated GPIIbIIIa (tau0), vWF was predominantly required
      at all G (63-75% inhibition by anti-vWF Ab), together with TSP (35-50% inhibition
      by anti-TSP Ab). Under these conditions, Fg was extensively converted to fibrin,
      so that fibrin, rather than Fg, could participate in microaggregation, with GPIb
      less required than GPIIbIIIa as indicated by a 30-60% inhibition by Ab 6D1 as
      compared to 100% inhibition by Ab 10E5. Our results show that interactions
      between multiple ligands and receptors favour microaggregation depending on shear
      and thrombin activation conditions.

PMID- 11522019
TI  - Platelets and phospholipids in tissue factor-initiated thrombin generation.
AB  - The influence of platelets on tissue factor (TF)-initiated thrombin generation in
      a reconstituted model of blood coagulation and in whole blood was evaluated. No
      thrombin generation was observed over 15 min in the reconstituted model when
      either TF or platelets and phospholipids were omitted. At 25 pM TF, the rates of
      thrombin generation were platelet and PCPS concentration-dependent and achieved
      maximum (1.0 nM/s) in the physiological range of platelet concentration. Similar
      rates were achieved in the absence of platelets when 1-2 microM phospholipid was
      used. However, the maximum rates of thrombin generation (5.2-6.0 nM/s) and the
      shortest initiation phase (1 min) were attained between 25 and 100 microM
      phospholipid. In the reconstituted model, an increase in platelet concentration
      from 0.125 x 10(8)/ml to 0.5 x 10(8)/ml decreased the duration of the initiation
      phase (in the absence of phospholipids) from 4.3 min to 2 min. Further increases
      in platelet concentration did not affect this phase. Sequential whole blood
      studies were conducted in blood of a chemotherapy patient who developed reduced
      platelet counts. The TF (12.5 pM) initiated clotting of patient's blood was
      accelerated from approximately 10 min to 5 min when the platelet concentration
      increased from 0.05 x 10(8)/ml to 0.11 x 10(8)/ml. Clotting times were
      essentially unchanged for platelet concentrations exceeding 0.5 x 10(8)/ml (range
      0.5-3.1 x 10(8)/ml). Similarly, clotting of whole blood obtained from healthy
      volunteers was not affected by the platelet count, which varied from 1.5 x
      10(8)/ml to 3.1 x 10(8)/ml (4.0+/-0.5 min). The data obtained in both models are
      consistent with in vivo observations that clinical bleeding is most likely to
      occur at platelet counts <0.1 x 10(8)/ml.

PMID- 11522020
TI  - Serial determinations of platelet counts in mice by flow cytometry.
AB  - Elucidation of the pathophysiological basis of platelet disorders in murine
      models requires a reliable method for the frequent determinations of platelet
      counts in individual mice. Here, we present a rapid, reproducible and accurate
      flow cytometric method for enumeration of platelets that involves fluorescent
      staining of platelets in whole blood with specific antibody and the addition of
      known numbers of fluorescent beads for standardization of the sample volume.
      Analysis of platelets obtained by tail bleeding indicated that this sampling
      procedure did not activate platelets, and that only five microliters of blood
      were required for platelet counting. Using this method, we followed platelet
      counts in mice infected with the relapsing fever spirochete Borrelia turicatae
      for 26 days, and found that this bacterium induces thrombocytopenia, a common
      manifestation of human relapsing fever. Therefore, this method can be used to
      follow the number and the activation state of circulating platelets from
      individual mice over extended periods of time and is applicable to a wide range
      of murine models of platelet disorders.

PMID- 11522021
TI  - Human endothelial cell-derived nuclear proteins that recognise polymorphic DNA
      elements in the von Willebrand factor gene promoter include YY1.
AB  - Four common base-change polymorphisms have been found in the von Willebrand
      factor gene promoter: (-1793 C/G, -1234 T/C, -1185 G/A and -1051 A/G). All four
      polymorphisms are in strong linkage disequilibrium and recent reports have
      indicated these polymorphisms are associated with plasma vWF:Ag levels suggesting
      that one or more of these elements influence regulation of the vWF gene. We
      report that human endothelial cell-derived trans-acting factors display allelic
      preferences in binding activity to each polymorphic site. The common A allele
      variant of the -1051 polymorphism and the rarer A allele variant of the -1185
      polymorphism provided specific binding of nuclear proteins. The G allele
      counterpart of these two variants did not produce any complex formation
      indicating that the nucleotide substitution at these positions alters the DNA
      binding ability of nuclear factors. The two alleles of the -1234 polymorphism
      produced two complexes with a similar migration pattern however stronger binding
      was found to the common T variant of this allele. Two specific complexes
      associated with the rarer G allele of the -1793 polymorphism, but only one
      associated with the C allele. Supershift experiments revealed that the trans
      acting factor YYI recognised the slower migrating complex formed on the -1234 T/C
      and the -1051 A polymorphic sites with a strong binding preference for the -1234
      T allele variant. The identification of YY1 as a component of the factors that
      recognise these elements suggests that this ubiquitous nuclear protein may play a
      role in the regulation of the vWF promoter.

PMID- 11522022
TI  - Glucose and insulin modulate the capacity of endothelial cells (HUVEC) to express
      P-selectin and bind a monocytic cell line (U937).
AB  - Diabetes mellitus is associated with increased prevalence of endothelial cell
      dysfunction and vascular diseases. Mechanisms leading to alterations in
      endothelial cell function are poorly understood. We report here that
      hyperglycaemia results in the expression of endothelial adhesion molecules
      involved in leukocyte adhesion and extravasation. Incubation of human umbilical
      cord endothelial cells (HUVEC) with 25 mM glucose induced the expression of P
      selectin. This effect was reversed by the addition of 1 nM insulin. Moreover,
      increased ICAM-1 expression was observed upon HUVEC incubation with 25 mM
      glucose. Increased adhesion of U937 cells (a monocytic cell line) to endothelial
      cells cultured with 25 mM glucose was observed. High glucose-induced monocytes
      cell adhesion was inhibited by an anti-P-selectin monoclonal antibody (LYP20).
      These results show that high glucose concentration activates endothelial cells
      leading to monocytes adhesion providing further evidence that hyperglycaemia
      might be implicated in vessel wall lesions contributing to diabetic vascular
      disease.

PMID- 11522023
TI  - Release of soluble urokinase receptor from vascular cells.
AB  - Urokinase-type plasminogen activator (uPA) and its cell surface-receptor (uPAR)
      regulate cellular functions linked to adhesion and migration and contribute to
      pericellular proteolysis in tissue remodelling processes. Soluble uPAR (suPAR) is
      present in the circulation, peritoneal and ascitic fluid and in the cystic fluid
      from ovarian cancer. We have investigated the origin and the vascular
      distribution of the soluble receptor, which accounts for 10-20% of the total
      receptor in vascular endothelial and smooth muscle cells. Phase separation
      analysis of the cell conditioned media with Triton X-114 indicated that suPAR
      associates with the aqueous phase, indicative of the absence of the glycolipid
      anchor. There was a polarized release of suPAR from cultured endothelial cells
      towards the basolateral direction, whereas the membrane-bound receptor was found
      preferentially on the apical surface. Both, uPAR and suPAR became upregulated 2-4
      fold after activation of protein kinase C with phorbol ester, which required de
      novo protein biosynthesis. Interleukin-1beta (IL-1beta), basic fibroblast growth
      factor (bFGF) or vascular endothelial growth factor increased suPAR release from
      endothelial cells, whereas platelet derived growth factor-BB, bFGF or IL-1beta
      stimulated suPAR release from vascular smooth muscle cells. Immune electron
      microscopy indicated that in atherosclerotic vessels (s)uPAR was observed on cell
      membranes as well as in the extracellular matrix.  These findings indicate that
      (s)uPAR from vascular cells is upregulated by proangiogenic as well as
      proatherogenic growth factors and cytokines, is preferentially released towards
      the basolateral side of endothelial cells and accumulates in the vessel wall.

PMID- 11522025
TI  - Synergistic induction of t-PA by vascular endothelial growth factor and basic
      fibroblast growth factor and localization of t-PA to Weibel-Palade bodies in
      bovine microvascular endothelial cells.
AB  - Endothelial cell migration is stimulated by members of the vascular endothelial
      growth factor (VEGF) and basic fibroblast growth factor (bFGF) families, and is
      dependent on extracellular proteolytic activity provided by enzymes of the
      plasminogen activator (PA) system. Here we report that in bovine microvascular
      endothelial cells (BME cells), bFGF principally increased urokinase-type PA (u
      PA) while tissue-type PA (t-PA) was increased mainly by VEGF. In bovine aortic
      endothelial cells (BAE cells), bFGF increased u-PA, whereas VEGF had no effect.
      Co-added bFGF and VEGF increased t-PA mRNA levels and enzyme activity in both
      cell types in a synergistic manner. Tissue-type plasminogen activator (t-PA)
      immunoreactivity colocalized with von Willebrand factor, a marker for Weibel
      Palade bodies. Co-added bFGF and VEGF increased the number of t-PA-positive cells
      as well as the number of t-PA-positive granules per cell. Localization of t-PA in
      regulated storage granules endows endothelial cells with the potential to rapidly
      increase proteolytic activity in the pericellular environment.

PMID- 11522024
TI  - A monoclonal antibody to platelet type III collagen-binding protein (TIIICBP)
      binds to blood and vascular cells, and inhibits platelet vessel-wall
      interactions.
AB  - TIIICBP is a new platelet receptor involved in platelet-type III collagen and
      platelet-subendothelium interactions. This receptor is composed of a doublet of
      72-68 kDa proteins. In this study, the major protein (68 kDa) was purified and
      used to produce monoclonal antibodies. One of these antibodies, 7F4, binds to
      platelets as confirmed by flow cytometry. 7F4 inhibited platelet contact,
      spreading and aggregation induced by type III collagen. Under flow conditions,
      7F4 prevented platelet interactions with type III collagen, endothelial cell
      matrix and the KOGEOGPK type II collagen octapeptide: the specific sequence
      recognized by TIIICBP. On the other hand, 7F4 had no effect on platelet-type I
      collagen interactions. TIIICBP was also detected on lymphocytes, granulocytes and
      monocytes. TIIICBP was expressed on endothelial cells and fibroblasts but not on
      smooth-muscle cells. These results show that TIIICBP is expressed on several cell
      types and participates in cell adhesion to the subendothelium.

PMID- 11522026
TI  - Classification and nomenclature of prothrombin activators isolated from snake
      venoms.

PMID- 11522027
TI  - Recommended abbreviations for von Willebrand Factor and its activities.

PMID- 11522028
TI  - The effects of transdermal and oral estrogen/progesterone regimens on free and
      total protein S in postmenopausal women.

PMID- 11522029
TI  - No increased risk of venous thrombosis in women taking tranexamic acid.

PMID- 11522030
TI  - Reassessment of the correlation between the von Willebrand Factor activity, the
      PFA-100, and the bleeding time in patients with von Willebrand disease.

PMID- 11522031
TI  - A new mutation trans to I278T cystathionine beta-synthase associated with Factor
      V Leiden causes mild homocystinuria but severe vascular disease.

PMID- 11522032
TI  - Molecular identity of platelet CD40 ligand (CD40L).

PMID- 11522033
TI  - Hallmark discoveries on TAFI date back to 1968.

PMID- 11522034
TI  - Efficacy of intravenous vitamin K in a case of massive warfarin overdosage.

PMID- 11522035
TI  - Economic impact of the introduction of the ProC Global assay in the screening
      strategy of protein C pathway abnormalities in unselected patients with a history
      of venous thromboembolism.

PMID- 11522036
TI  - Antithrombin does not directly promote the endothelial production of prostacyclin
      in cultured endothelial cells.

PMID- 11522037
TI  - High prevalence of Factor V Leiden mutation among healthy individuals and
      patients with deep venous thrombosis in Lebanon: is the eastern Mediterranean
      region the area of origin of this mutation?

PMID- 11522038
TI  - Rebuttal to: The usefulness of compression ultrasonography of the lower limbs in
      patients with a clinical suspicion of pulmonary embolism.

PMID- 11522039
TI  - The usefulness of compression ultrasonography of the lower limbs in patients with
      a clinical suspicion of pulmonary embolism.

PMID- 11522040
TI  - An ideal biological marker of Alzheimer's disease: dream or reality?
AB  - Senile dementia of Alzheimer's type (AD) is commonly characterized as a
      neurodegenerative disorder, which exhibits gradual changes of consciousness, loss
      of memory, perception and orientation as well as loss of personality and
      intellect. AD prevalence increases dramatically with age and is the fourth cause
      of death in Europe and in the USA. Currently, there are no available biological
      markers, which gives clinicians no other alternative than to rely upon clinical
      diagnosis by exclusion. There is no assay of objective ante mortem biochemical
      phenomena that relate to the pathophysiology of this disease. The pathophysiology
      of AD is connected with alterations in neurotransmission, plaque formation,
      cytoskeletal abnormalities and disturbances of calcium homeostasis. The search
      for a test, which is non-invasive, simple, cheap and user-friendly, should be
      directed at accessible body fluids. Only abnormalities replicated in large series
      across different laboratories fulfilling the criteria for a biological marker are
      likely to be of relevance in diagnosing AD. To date, only the combination of
      cerebrospinal fluid tau and Abeta42 most closely approximate an ideal biomarker
      of Alzheimer's disease. A short review on the role of biological markers in AD on
      the basis of the literature, contemporary knowledge and our own recent findings
      are presented.

PMID- 11522041
TI  - Antibodies against oxidized LDL--theory and clinical use.
AB  - Modification of low density lipoprotein (LDL) particles due to oxidation,
      glycation and binding of advanced glycation end-products (AGEs) or
      malondialdehyde (MDA, a final product of lipid peroxidation) is considered most
      important in the process of atherogenesis. Oxidatively modified LDL are
      distinguished by another receptor type, which was discovered on the surface of
      macrophages and was called the scavenger receptor. Uncontrolled intake of LDL
      converts macrophages to foam cells; their accumulation under the vascular
      endothelium is considered as the first stage of atherosclerosis. Oxidation of LDL
      is a complex process taking place in both the extra- and intracellular space. At
      the end of this oxidative process, modified LDL particles show chemotactic,
      cytotoxic and immunogenic properties. Oxidized LDL express a large number of
      epitopes and cause production of polyclonal autoantibodies against these
      products, especially against apoB100 modified by MDA and 4-hydroxynonenal.
      IgoxLDL (antibodies against oxidized LDL) can be demonstrated either directly in
      intimal lesions or as a component of circulating immune complexes. IgoxLDL do not
      form a homogeneous group but a varied mixture of antibodies-isoantibodies caused
      by HDL and LDL polymorphism, antibodies against the lipid phase of LDL and
      antibodies against modified apoB100 of the immunoglobulin class IgA or IgG.
      Antibodies against oxLDL were found in many diseases other than atherosclerosis
      such as diabetes mellitus, renovascular syndrome, uremia, rheumatic fever, morbus
      Bechtjerev or lupus erythematodes. Newborns have practically the same levels of
      IgoxLDL as their mothers; however, these values did not differ from those in the
      healthy population of non-pregnant women of the same age. The decrease in IgoxLDL
      titer was very slow and lasted many months; that is why this parameter cannot be
      considered suitable for describing the rapid changes during oxidative stress of
      the organism. Positive correlation of IgoxLDL with antiphospholipids and other
      antibodies was repeatedly demonstrated; their determination can thus be used as a
      marker for the description of total production of autoantibodies in various
      diseases. The changes and correlations of IgoxLDL, anti-beta-2-glycoprotein I IgG
      and antiphospholipid antibodies support the immunological link between thrombotic
      and atherosclerotic processes in the human body.

PMID- 11522042
TI  - Effect of ACE inhibitor captopril and L-arginine on the metabolism and on
      ischemia-reperfusion injury of the isolated rat heart.
AB  - We investigated the effects of in vivo treatment with the angiotensin-converting
      enzyme inhibitor (ACE-I) captopril and/or of in vitro administration of L
      arginine on the metabolism and ischemia-reperfusion injury of the isolated
      perfused rat myocardium. Captopril (50 mg/l in drinking water, 4 weeks) raised
      the myocardial content of glycogen. After 25-min global ischemia, captopril
      treatment, compared with the controls, resulted in lower rates of lactate
      dehydrogenase release during reperfusion (8.58 +/- 1.12 vs. 13.39 +/- 1.88
      U/heart/30 min, p<0.05), lower myocardial lactate contents (11.34 +/- 0.93 vs.
      21.22 +/- 4.28 micromol/g d.w., p<0.05) and higher coronary flow recovery (by
      25%), and prevented the decrease of NO release into the perfusate during
      reperfusion. In control hearts L-arginine added to the perfusate (1 mmol/l) 10
      min before ischemia had no effect on the parameters evaluated under our
      experimental conditions, presumably because of sufficient saturation of the
      myocardium with L-arginine. In the hearts of captopril-treated rats, L-arginine
      further increased NO production during reperfusion and the cGMP content before
      ischemia. Our results have shown that long-term captopril treatment increases the
      energy potential and has a beneficial effect on tolerance of the isolated heart
      to ischemia. L-arginine added into the perfusate potentiates the effect of
      captopril on the NO signaling pathway.

PMID- 11522043
TI  - Hyperoxia and recovery from hypoxia alter collagen in peripheral pulmonary
      arteries similarly.
AB  - Chronic hypoxia causes pulmonary hypertension, the mechanism of which includes
      altered collagen metabolism in the pulmonary vascular wall. This chronic hypoxic
      pulmonary hypertension is gradually reversible upon reoxygenation. The return to
      air after the adjustment to chronic hypoxia resembles in some aspects a hyperoxic
      stimulus and we hypothesize that the changes of extracellular matrix proteins in
      peripheral pulmonary arteries may be similar. Therefore, we studied the exposure
      to moderate chronic hyperoxia (FiO2 = 0.35, 3 weeks) in rats and compared its
      effects on the rat pulmonary vasculature to the effects of recovery (3 weeks)
      from chronic hypoxia (FiO2 = 0.1, 3 weeks). Chronically hypoxic rats had
      pulmonary hypertension (Pap = 26 +/- 3 mm Hg, controls 16 +/- 1 mm Hg) and right
      ventricular hypertrophy. Pulmonary arterial blood pressure and right ventricle
      weight normalized after 3 weeks of recovery in air (Pap = 19 +/- 1 mm Hg). The
      rats exposed to moderate chronic hyperoxia also did not have pulmonary
      hypertension (Pap = 18 +/- 1 mm Hg, controls 17 +/- 1 mm Hg). Collagenous
      proteins isolated from the peripheral pulmonary arteries (100-300 microm) were
      studied using polyacrylamide gel electrophoresis. A dominant low molecular weight
      peptide (approx. 76 kD) was found in hypoxic rats. The proportion of this peptide
      decreases significantly in the course of recovery in air. In addition, another
      larger peptide doublet was found in rats recovering from chronic hypoxia. It was
      localized in polyacrylamide gels close to the zone of alpha2 chain of collagen
      type I. It was bound to anticollagen type I antibodies. An identically localized
      peptide was found in rats exposed to moderate chronic hyperoxia. The apparent
      molecular weight of this collagen fraction suggests that it is a product of
      collagen type I cleavage by a rodent-type interstitial collagenase (MMP-13). We
      conclude that chronic moderate hyperoxia and recovery from chronic hypoxia have a
      similar effect on collagenous proteins of the peripheral pulmonary arterial wall.

PMID- 11522044
TI  - Efficiency of NO donors in substituting impaired endogenous NO production: a
      functional and morphological study.
AB  - Two exogenous NO donors were used to act as substitutes for impaired endogenous
      nitric oxide (NO) production due to inhibition of NO synthase in rats. Six weeks'
      lasting inhibition of NO synthase by NG-nitro-L-arginine methyl ester (L-NAME)
      induced stabilized hypertension. Simultaneously administered isosorbide-5
      mononitrate did not prevent the development of hypertension. Molsidomine,
      administered concomitantly with L-NAME, significantly attenuated the BP increase.
      However, BP was still found to be moderately increased compared to the initial
      values. Remarkable alterations in the geometry of the aorta, carotid and coronary
      artery found in NO-deficient hypertension were prevented in rats administered L
      NAME plus molsidomine at the same time. In spite of 6 weeks' lasting inhibition
      of NOS, the NOS activators acetylcholine and bradykinin induced BP decrease; the
      maximum hypotensive value did not differ from the values recorded in the controls
      or in animals treated with L-NAME plus molsidomine. Notably enough, the
      hypotension was similar to that found in rats administered L-NAME alone for six
      weeks. After NO synthase inhibition, Isosorbide-5-mononitrate does not substitute
      and molsidomine substitute only partially the impaired endogenous NO production.

PMID- 11522045
TI  - Terguride attenuates prolactin levels and ameliorates insulin sensitivity and
      insulin binding in obese spontaneously hypertensive rats.
AB  - Glucose tolerance, serum insulin, insulin receptors in epididymal fat tissue,
      circulating total cholesterol and triglyceride concentrations as well as serum
      prolactin were studied in obese and lean spontaneously hypertensive rats (SHR) of
      both sexes. Obese animals displayed insulin resistance and elevated insulin and
      triglyceride concentrations. Moreover, in obese rats the increased mass of
      epididymal fat tissue was accompanied with decreased capacity of high affinity
      binding sites of insulin receptors in the tissue plasma membranes. Terguride
      treatment lowered prolactin serum levels which was accompanied by ameliorated
      insulin sensitivity in obese animals of both sexes. In addition, terguride
      treatment decreased serum insulin and triglyceride concentrations in obese
      females and at the same time enhanced the affinity of high affinity insulin
      binding sites. Our results show that obesity in SHR is associated with a
      decreased capacity of insulin receptors and that prolactin may play a role in
      obesity-induced insulin resistance, particularly in female rats.

PMID- 11522046
TI  - Effect of leptin and insulin on chick embryonic muscle cells and hepatocytes.
AB  - In the present study we used the primary cultures of chick embryonic muscle and
      liver cells as a model for potential mutual combination effects of leptin and
      insulin, respectively. The influence of both homones on the proliferation and
      protein synthesis was dose-dependent and related to the age of embryos from which
      the cells were isolated. Leptin (10 and 100 ng/well) increased the proliferation
      (estimated by DNA content and incorporation of labeled thymidine into DNA) and
      protein synthesis (determined by incorporation of labeled leucine into proteins)
      of muscle cells. The effect of leptin and insulin in muscle cells was similar. In
      younger embryo (11-day-old) the lower dose of leptin was more effective than the
      higher one compared to the insulin effect. Mutual effects of leptin and insulin
      were neither additive nor synergistic and were equivalent to the effects of
      individual hormones. In hepatocytes the influence of leptin was dependent on the
      age at which the cells were isolated (11- and 19-day-old embryos). The presence
      of insulin neither potentiated nor inhibited the effect of leptin.

PMID- 11522048
TI  - Different influence of hypodynamy on calcium and phosphorus levels in bones of
      male and female Japanese quails.
AB  - The influence of long-term hypodynamy on the calcium and phosphorus levels was
      studied in the bones of Japanese quails. The hypodynamy evoked different changes
      in the calcium and phosphorus content in males and females. The calcium content
      in the marrow of femurs was only changed in the hens, while in cockerels it was
      significantly decreased in the upper part and marrow of the tibia. Furthermore,
      changes in the phosphorus content were observed only in the tibia of cockerels.

PMID- 11522047
TI  - Influence of amiodarone on urinary excretion of 6beta-hydroxycortisol in humans.
AB  - The present study was undertaken to evaluate the use of cortisol 6beta
      hydroxylation in defining the effect of amiodarone on cytochrome CYP3A activity.
      To accomplish this goal, the in vivo activity of CYP3A was estimated by measuring
      the 24-hour urinary excretion of 6beta-hydroxycortisol (6beta-OHC) and by
      calculating 24-hour ratio of 6beta-hydroxycortisol to urinary free cortisol
      (6beta-OHC/UFC ratio). Nine cardiac patients scheduled for amiodarone treatment
      were recruited to participate in this study. Urine was collected over a 24-hour
      period from each subject before the first amiodarone administration and during
      the third day of oral administration of amiodarone (200 mg four times daily as a
      loading dose). Three days of amiodarone treatment caused a significant decrease
      (p<0.05) in both the 6beta-OHC/UFC ratio and the 24-hour urinary excretion of
      6beta3-OHC. These results suggest that amiodarone is an inhibitor of CYP3A
      activity.

PMID- 11522049
TI  - Excitotoxicity of lathyrus sativus neurotoxin in leech retzius neurons.
AB  - The effects of Lathyrus sativus neurotoxin were studied on the cell membrane
      potential and cellular cation composition in Retzius nerve cells of the leech
      Haemopis sanguisuga, with ion-selective microelectrodes using liquid ion
      exchangers. Bath application of 10(-4) mol/l Lathyrus sativus neurotoxin for 3
      min depolarized the cell membrane potential and decreased the input resistance of
      directly polarized membrane in Retzius neurons. At the same time the cellular Na+
      activity increased and cellular K+ activity decreased with slow but complete
      recovery, while the intracellular Ca2+ concentration was not changed. Na+-free
      Ringer solutions inhibited the depolarizing effect of the neurotoxin on the cell
      membrane potential. Zero-Ca2+ Ringer solution or Ni2+-Ringer solution had no
      influence on the depolarizing effect of the neurotoxin on the cell membrane
      potential. It is obvious that the increase in membrane conductance and
      depolarization of the cell membrane potential are due to an influx of Na+ into
      the cell accompanied by an efflux of K+ from the cell.

PMID- 11522050
TI  - Excitability changes of cortical neurons during the postnatal period in rats
      exposed to prenatal hypobaric hypoxia.
AB  - Pregnant rats were exposed to intermittent hypobaric hypoxia (at a simulated
      altitude of 7000 m or 5000 m) and the excitability of cortical neurons of their
      pups was tested. Stimulation of the sensorimotor cortex of rats prenatally
      exposed to hypoxia shortened the duration of cortical afterdischarges in 12-day
      old rats, but did not change the excitability in 25-day-old animals. Shortening
      of the first afterdischarge in 35-day-old rats but the prolongation of the first
      afterdischarge in adult rats (as compared to the duration of cortical
      afterdischarges in rats not exposed to prenatal hypoxia) were registered. The
      possible mechanisms of different excitability of cortical neurons in rats
      prenatally exposed to hypobaric hypoxia are discussed.

PMID- 11522051
TI  - Analyses of lindane, vinclozolin, aldrin, p,p'-DDE, o,p'-DDT and p,p'-DDT in
      human serum using gas chromatography with electron capture detection and tandem
      mass spectrometry.
AB  - A sensitive, selective and reliable procedure was developed and validated to
      determine organochlorinated compounds, which present endocrine-disrupting
      effects, lindane, vinclozolin, aldrin, p,p'-DDT, o,p'-DDT and p,p'-DDE, in human
      serum. The analytical methodology combines serum extraction with organic
      solvents, clean-up of the organic extract using acid treatment with H2SO4,
      elution of the cleaned-up extract through liquid column chromatography system and
      analysis of the fraction eluted by gas chromatography (GC) with electron capture
      detection (ECD) and tandem mass spectrometry (MS-MS) detection mode. Performance
      characteristics, such as linearity, sensitivity, precision, accuracy or recovery,
      of both chromatographic methods were studied. The proposed analytical methodology
      was applied to analyse the target compounds in serum samples from women living in
      agricultural areas of Almeria (Spain). Comparison of the MS-MS and the ECD
      results was made and the advantage of the MS-MS operation mode to determine
      endocrine disrupting compounds in complex matrices is also presented.

PMID- 11522052
TI  - Simultaneous determination of unbound ropivacaine in rat blood and brain using
      microdialysis.
AB  - To investigate the pharmacokinetics of ropivacaine in rat blood and brain, a
      sensitive HPLC method and microdialysis were developed for the simultaneous
      determination of unbound ropivacaine in rat blood and brain. Adult, male Sprague
      Dawley rats (290-350 g) were anesthetized with sodium pentobarbital (50 mg/kg,
      i.p.). Two microdialysis probes were inserted, one into the jugular vein toward
      right atrium, and one into the brain striatum of rats. Ropivacaine (5 mg/kg,
      i.v.) was then administered via the femoral vein. Blood and brain dialysates were
      collected and eluted with a mobile phase containing methanol-acetonitrite-20 mM
      monosodium phosphoric acid (pH 5.5) (10:40:50, v/v/v) in a liquid chromatographic
      system. Separation of ropivacaine was achieved by a CN column (Phenomenex Luna,
      250x4.6 mm, particle size 5 microm; Torrance, CA, USA) within 10 min. The UV
      detector wavelength was set at 205 nm and the detection limit of ropivacaine was
      20 ng/ml. The intra- and inter-day accuracy and precision of the analyses were
      less than 10% in the ranges of 0.02-5 microg/ml. The pharmacokinetic data were
      calculated from the individual animal measurements of dialysate concentration
      versus time. This method exhibits no endogenous interference and its sensitivity
      is sufficient for the determination of biological samples. The present results
      confirm that microdialysis sampling followed by LC separation with UV detection
      represents a viable approach for the measurement of free ropivacaine in rat brain
      and plasma.

PMID- 11522053
TI  - Seasonal differences in ram seminal plasma revealed by partition in an aqueous
      two-phase system.
AB  - Seminal plasma plays an important role in maturation of spermatozoa through
      hormonal, enzymatic and surface-modifying events. We have previously shown that
      adsorption of seminal plasma proteins (SPPs) to the sperm cell surface partially
      restores the functional characteristics of damaged spermatozoa, reproducing those
      of live cells. In the present report, we investigate the hypothesis that seasonal
      differences in seminal plasma could affect its ability to recover membrane
      integrity of cold-shocked sperm. The effect of seminal plasma proteins, obtained
      in breeding (bsSPPs) and non-breeding (nbsSPPs) season, on cold-shocked ram
      spermatozoa previously freed from seminal plasma, was analysed by centrifugal
      counter-current distribution (CCCD) in an aqueous two-phase system as well as
      membrane integrity determination by fluorescence markers. Cold-shock treatment
      greatly lowered cell viability in both breeding and non-breeding season
      spermatozoa. The cold-shocked sperm viability obtained was approximately 20%. The
      loss of heterogeneity and the decrease in viability revealed by CCCD analysis was
      reversed by the addition of increasing amounts of bsSPP, which induced
      restoration of the surface characteristics of viable-like spermatozoa, as well as
      an increase in the number of recovered viable sperm. However, this restoring
      effect was much lower when nbsSPPs were added, even in a sixfold higher
      concentration than used with bsSPPs. Incubation of cold-shocked cells with both
      kinds of proteins performed in both seasonal periods, showed that the recovering
      effect was related to the season when the plasma sample was obtained rather than
      to the semen season. The addition of bsSPPs to cold-shocked sperm accounted for a
      nearly 50% reversion for both studied breeding seasons. However, the reversion
      percentages obtained with nbsSPPs were significantly lower (P<0.05) than those
      found with bsSPPs in both studied seasonal periods. This different reversion
      capacity of bsSPPs and nbsSPPs was related to a different protein composition, as
      revealed by comparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis
      analysis. The bands of 20, 21, 24, 36 and 67 kDa of the bsSP sample profile
      decreased in winter-spring SP, and were even less intensely stained in summer SP.
      Densitometric analysis of the stained gel patterns allows automatic comparison
      among the separated bands, and revealed an important decrease in the content of
      several bands. The 21.5 kDa band showed the highest decrease, lowering to 14% in
      June-August plasma with respect to the value obtained in September-December
      plasma.

PMID- 11522054
TI  - Determination of sameridine in blood plasma by nitrogen-selective gas
      chromatography.
AB  - A gas chromatographic method was developed and validated for the determination of
      sameridine in human plasma. Sameridine is a new type of compound with both local
      anaesthetic and analgesic properties, when administered intrathecally. The method
      is based on liquid-liquid extraction of sameridine from 1.0 ml of plasma,
      followed by gas chromatography with nitrogen-phosphorus detection. Method
      validation results showed that this method is very sensitive, selective and
      robust. The limit of quantification was 1 nM for 1.0 ml of human plasma in the
      low-level range (1.00-75.0 nM) and the between-day accuracy and precision were
      measured at 99-104% of nominal values and 3.4-5.6% (RSD), respectively.

PMID- 11522055
TI  - Immobilised metal-ion affinity chromatography purification of histidine-tagged
      recombinant proteins: a wash step with a low concentration of EDTA.
AB  - Immobilised metal-ion affinity chromatography (IMAC) is widely used for the
      purification of recombinant proteins in which a poly-histidine tag is introduced.
      However, other proteins may also bind to IMAC columns. We describe the use of a
      washing buffer with a low concentration of EDTA (0.5 mM) for the removal of
      proteins without histidine tag from IMAC columns. Four histidine-tagged
      recombinant proteins/protein complexes were purified to homogeneity from cell
      culture medium of insect cells by using an EDTA washing buffer. The presence of a
      low concentration of EDTA in washing buffers during IMAC may have a general
      application in the purification of histidine-tagged proteins.

PMID- 11522056
TI  - Polyhydroxyethylmethacrylate-based magnetic DNA-affinity beads for anti-DNA
      antibody removal from systemic lupus erythematosus patient plasma.
AB  - The aim of this study is to prepare magnetic poly(2-hydroxyethylmethacrylate)
      (mPHEMA) beads and to investigate their utility for the removal of anti-DNA
      antibodies from systemic lupus erythematosus (SLE) patient plasma. mPHEMA beads,
      in the size range of 80-120 microm, were produced by a modified suspension
      technique. Then, DNA was coupled onto mPHEMA beads by carbodiimide activation.
      The amount of ligand coupled was changed by changing the initial concentrations
      of carbodiimide and DNA. Human immunoglobulin G (HIgG) and anti-DNA antibody
      adsorption from aqueous solutions and human plasma were examined in a batch
      system. mPHEMA beads were characterized by swelling tests, electron spin
      resonance (ESR) and scanning electron microscopy. Important results obtained in
      this study are as follows: the swelling ratio of mPHEMA beads was 34%. The
      presence of magnetite particles in the polymeric structure was confirmed by ESR.
      The mPHEMA beads have a spherical shape and porous structure. Maximum DNA
      coupling of carbodiimide activated mPHEMA beads was 4.4 mg/g. Maximum HIgG
      adsorption from an aqueous solution was 47.5 mg/g. Anti-DNA antibody adsorption
      from SLE plasma was observed as 87.6 mg/g. Non-specific HIgG adsorption was 0.1
      mg/g. More than 90% of the adsorbed HIgG molecules and anti-DNA antibodies were
      desorbed succesfully by using NaSCN solution. It was possible to reuse these DNA
      affinity beads without significant losses in the antibody adsorption capacities.

PMID- 11522057
TI  - Diagnostic patterns of very-long-chain fatty acids in plasma of patients with X
      linked adrenoleukodystrophy.
AB  - Pattern recognition analysis on the levels of the very-long-chain fatty acids
      (VLCFAs) in plasma is described for the visual discrimination of X-linked
      adrenoleukodystrophy (X-ALD) patients from normal healthy group. Plasma VLCFA
      compositions of 58 normal subjects and 16 X-ALD patients were examined by gas
      chromatography as their methyl esters to determine the area percentages of
      behenic acid (C22:0), lignoceric acid (C24:0) and hexacosanoic acid (C26:0) in
      the total fatty acids, and the concentration (microg/ml) of C26:0. When star
      symbol plotting was applied to the VLCFA values of C22:0 (%), C24:0 (%), C26:0
      (%), C24:0/C22:0, C26:0/C22:0 and C26:0 (microg/ml) after normalization to the
      corresponding median values in normal group, the resulting deformed hexagonal
      star pattern was characteristic of each patient. Therefore, simple visual
      comparison with the equilateral hexagon of normal group average as the control
      pattern enabled one readily to discriminate X-ALD patients from the normal group.
      Additionally, canonical discriminant analysis performed on the six unnormalized
      VLCFA values correctly classified 74 plasma specimens into two separate clusters
      according to normal subject or X-ALD patient in the canonical plot.

PMID- 11522058
TI  - Simultaneous determination of six adenyl purines in human plasma by high
      performance liquid chromatography with fluorescence derivatization.
AB  - A sensitive method was developed for the simultaneous determination of six adenyl
      purines in human plasma by high-performance liquid chromatography. The adenyl
      purines (adenine, adenosine, AMP, ADP, ATP and cyclic AMP) were derivatized using
      2-chloroacetaldehyde for fluorescence detection, and the reaction and separation
      conditions were reinvestigated to improve sensitivity for small volume sample
      analysis. Each derivatized purine was separated on a Capcell Pack SG120A column
      with mobile phase consisting of 0.05 M citric acid-0.1 M dipotassium hydrogen
      phosphate (pH 4.0)-methanol (97+3). The detection limits were 100-1000 fmol/ml by
      fluorescence detection, some 500 times better than previous reports. The proposed
      method was applied to determine adenyl purines in human plasma. The purine levels
      were as follows: ATP (9.2-22.2 pmol/ml), ADP (5.5-22.2 pmol/ml), AMP (0.8-3.2
      pmol/ml). Other purines, adenine, adenosine, cAMP were lower than 0.1 pmol/ml.

PMID- 11522059
TI  - Separation of some mono-, di- and tri-unsaturated fatty acids containing 18
      carbon atoms by high-performance liquid chromatography and photodiode array
      detection.
AB  - Positional and geometric isomers of mono-, di- and tri-unsaturated fatty acids
      containing 18 carbon atoms were separated on commercially available reversed
      phase columns in gradient systems composed of acetonitrile and water, utilizing
      photodiode array detection. The biological samples were hydrolyzed with 2 M NaOH
      for 35-40 min at 85-90 degrees C. After cooling, the hydrolysates were acidified
      with 4 M HCl and the free fatty acids were extracted with dichloromethane. The
      organic solvent was removed in a gentle stream of argon. The fatty acids were
      determined after pre-column derivatization with dibromacetophenone in the
      presence of triethylamine. The reaction components were mixed and reacted for 2 h
      at 50 degrees C. Separations of derivatized fatty acids were performed on two C18
      columns (Nova Pak C18, 4 microm, 250x4.6 mm, Waters) by binary or ternate
      gradient programs and UV detection at 254 and 235 nm. The geometric and
      positional isomers of some unsaturated fatty acids were substantially retained on
      the C18 columns and were distinct from some saturated fatty acids, endogenous
      substances in biological samples or background interference. Only slight
      separation of critical pairs of cis-9 C18:1/cis-11 C18:1 and cis-6 C18:1/trans-11
      C18:1 was obtained. A ternate gradient program can be used for complete
      fractionation of a mixture of conjugated linoleic acid isomers (CLA) from cis-9,
      cis-12 and trans-9, trans-12 isomers of C18:2. The CLA isomers in the effluent
      were monitored at 235 nm. The CLA isomers were differentiated from saturated and
      unsaturated fatty acids using a photodiode array detector. The utility of the
      method was demonstrated by evaluating the fatty acid composition of duodenal
      digesta, rapeseed and maize oils.

PMID- 11522060
TI  - Determination of fluvastatin and its five metabolites in human plasma using
      simple gradient reversed-phase high-performance liquid chromatography with
      ultraviolet detection.
AB  - A simple gradient reversed-phase high-performance chromatographic method with
      ultraviolet detection for the determination of fluvastatin (FV) and its five
      metabolites, (M-2, M-3, M4, M-5 and M-7) in human plasma was developed and
      validated. The limit of quantification of FV and its five metabolites in human
      plasma was 10 ng ml(-1). The assay had satisfactory selectivity, recovery,
      linearity and precision accuracy. Stability studies showed that FV and its five
      metabolites were stable in plasma up to at least 1 month of storage at -30
      degrees C.

PMID- 11522061
TI  - Determination of mevalonic acid in human urine as mevalonic acid lactone by gas
      chromatography-mass spectrometry.
AB  - Mevalonic acid in urine is converted to its lactone form by incubation overnight
      at acidic pH, extracted and analysed by GC-MS. The lower limit of quantitation of
      7.5 ng/ml provides adequate sensitivity to measure changes in urinary excretion
      of MVA following administration of drugs which affect cholesterol synthesis. The
      assay is linear up to 300 ng/ml and has acceptable precision (<15%) and accuracy
      (<+/-20%) across the calibration range.

PMID- 11522062
TI  - Matrix solid-phase dispersion technique for the determination of a new
      antiallergic drug, bilastine, in rat faeces.
AB  - A matrix solid-phase dispersion (MSPD) procedure for the isolation and HPLC
      determination of a new antiallergic agent, bilastine, in rat faeces is presented.
      The effect on recovery of empirical variables such as nature, pH and volume of
      the washing and elution liquids and nature of the adsorbent has been tested. The
      best recoveries were attained using an octadecylsilyl sorbent, 10 ml of a 0.1 M
      NaHCO3-Na2CO3 aqueous buffer of pH 10.0 as washing solvent and 10 ml of methanol
      as elution solvent. The extracts were evaporated to dryness and reconstituted in
      mobile phase before their injection into a HPLC system, equipped with a Discovery
      RP-amide C16 column and a fluorescence detector. The method allows one to reach
      recoveries of 95.0% within the concentration range 0.05-10 microg/g, with within
      day repeatabilities of less than 5% and between-day repeatabilities of less than
      9% within this range. This method has been successfully applied to the excretion
      studies of bilastine in the rat.

PMID- 11522063
TI  - Screening method for 11-nor-delta9-tetrahydrocannabinol-9-carboxylic acid in
      urine using hollow fiber membrane solvent microextraction with in-tube
      derivatization.
AB  - An efficient and inexpensive screening technique for the simultaneous clean-up,
      extraction, and derivatization of 11-nor-delta9-tetrahydrocannabinol-9-carboxylic
      acid (THC-COOH) from urine has been developed. Using the principles of solvent
      microextraction in the form of a 20-microl volume of solvent placed inside a
      permeable hydrophobic polypropylene hollow fiber membrane, the analyte of
      interest is preconcentrated inside this tubing as the bulk sample solution is
      stirred for a given extraction time. The pH of the sample is raised by adding
      buffer after which the charged moiety is extracted as an ion pair with
      tetramethylammonium hydrogen sulfate. Using a mixture of N,O
      bis(trimethylsilyl)trifluoroacetamide and octane as the extraction solvent allows
      the GC-unstable carboxylic acid metabolite to be derivatized during the
      extraction without prior sample clean-up steps such as filtration of the urine.
      After an 8-min extraction, a 6-microl portion is drawn up with a syringe and
      directly injected into a gas chromatograph for separation and analysis. Samples
      as low as 10 ng ml(-1) were analyzed successfully and the limit of detection was
      estimated at 1.0 ng ml(-1) with relative standard deviations lower than 10% in
      the final protocol.

PMID- 11522064
TI  - Determination of esmolol in serum by capillary zone electrophoresis and its
      monitoring in course of heart surgery.
AB  - A new Capillary Zone Electrophoresis (CZE) procedure for determination of
      esmolol, an ultra-short-acting beta-blocker, in serum was developed.
      Dichloromethane was applied as a deproteination agent and it was used also for
      the inactivation of erythrocytal esterase and in the same time for the extraction
      of esmolol from blood. The re-extraction of esmolol from organic phase to water
      phase was performed by 0.01 M HCl. An aliquot of 200 ml of acid aqueous phase was
      used for the injection and analysis. CZE determination was done in 50 mM
      phosphate buffer (pH=8.0) with detection at 222 nm. The concentration detection
      limit of esmolol in serum was 0.051 microg/ml. This method was applied in an
      extensive heart surgery experiment on pigs (Sus scrofa).

PMID- 11522065
TI  - Determination of a thermally labile metabolite of a novel growth hormone
      secretagogue in human and dog plasma by liquid chromatography with ion spray
      tandem mass spectrometric detection.
AB  - A sensitive and selective assay for the determination of N-[1(R)-[(1,2-dihydro-1
      methylsulfonylspiro[3H-indole-3,4'-piperidin]-1'-yl)carbonyl]-2-(phenylmethoxy)
      ethyl]-2-hydroxyamino-2-methylpropanamide (I), a hydroxyl amine metabolite of a
      novel growth hormone secretagouge (II) has been developed utilizing high
      performance liquid chromatography with ion spray tandem mass spectrometric
      detection (HPLC-MS-MS). The analyte and an internal standard (III) were isolated
      from the basified biological matrix using a liquid-liquid extraction with methyl
      tert.-butyl ether (MTBE). The organic extract was evaporated to dryness at room
      temperature. The residue was reconstituted in the mobile phase and injected into
      the HPLC-MS-MS system. Multiple reaction monitoring using the precursor-->product
      ion combinations of m/z 545-->267 and 543-->267 was used to quantify I and III,
      respectively, after chromatographic separation under isocratic conditions. The
      assay was validated in the concentration range of 0.5 to 500 ng/0.1 ml in both
      human and dog plasma. The precision of the assay, expressed as relative standard
      deviation, was less than 10% over the entire concentration range with the
      exception of the low concentration of 0.5 ng/0.1 ml which was 14.0% for human
      plasma. The HPLC-MS-MS method provided sufficient sensitivity to completely map
      the pharmacokinetic time course of I following a single 5 mg dose of II to human
      subjects and a 0.5 mg/kg dose to beagle dogs.

PMID- 11522066
TI  - Determination of N-acetylation phenotype using caffeine as a metabolic probe and
      high-performance liquid chromatography with either ultraviolet detection or
      electrospray mass spectrometry.
AB  - A rapid, sensitive method using liquid chromatography-electrospray mass
      spectrometry (LC-ES-MS) was developed and evaluated for the simultaneous
      quantitative determination of caffeine metabolites 1U, 1X and AAMU in human
      urine. This method involved a simple dilution of urine samples. The
      chromatographic separation was achieved on a C18 reversed-phase column using a
      gradient of acetonitrile in 2 mM, pH 3.0 ammonium formate as mobile phase. After
      ionisation in an electrospray source, mass spectrometric detection was performed
      in the negative ion, selected ion monitoring mode. This method yielded acceptable
      accuracy and precision within the range 0.25-50 microg/ml. This analytical method
      was applied to investigate the N-acetylator phenotype of HIV-infected patients
      and compared with high-performance liquid chromatography with UV detection. Its
      specificity was better, which appeared to be absolutely necessary to prevent
      errors in metabolic ratios and phenotype interpretation.

PMID- 11522067
TI  - Enhancement of phase separation using a drop coalescer in an aqueous two-phase
      system.
AB  - The effect of a drop coalescer on phase separation in a PEG/salt aqueous two
      phase system (ATPS) in the absence and presence of protein has been investigated.
      Raschig rings of ceramic, PTFE and glass were used as a drop coalescer in order
      to separate the mixture into two phases. Among the three materials PTFE is the
      most effective in coalescing the dispersed drops, with the throughput with PTFE
      being twice that without the coalescer. Random packing gives good results for
      phase separation. Two types of fiber mesh coated with PTFE were also used as drop
      coalescers, one in a spirally folded form and the other in a three-dimensional
      lattice-form. Throughput in the PEG/salt system with the three-dimensional
      lattice-form is 1.2 times as high as that with the spirally folded form.
      Throughput with the coalescer formed by compiling PTFE Raschig rings and fiber
      mesh in lattice form is 1.6 and 1.2 times as high as the case of separate use of
      the fiber mesh and the PTFE Raschig rings, respectively. The hydrophobic surface
      of PTFE in the compiled coalescer has no significant effect on the recovery
      fraction of the protein in ATPS.

PMID- 11522068
TI  - Speciation and metabolism of selenium injected with 82Se-enriched selenite and
      selenate in rats.
AB  - Selenate and selenite injected intravenously into rats were speciated by the HPLC
      ICP MS method with use of an enriched stable isotope as the tracer. In dose
      relation experiments, 82Se-enriched selenate or selenite was injected
      intravenously into male Wistar rats of 8 weeks of age (three rats/group) at
      single doses of 10, 25, 50, 100 and 200 microg/kg body weight for the selenate
      group, and 2, 5, 10, 25 and 50 microg/kg body weight for the selenite group. The
      animals were sacrificed 1 or 24 h later, and the concentrations and distributions
      of 82Se in the liver, kidneys, serum, and urine remaining in the bladder or 24-h
      urine were determined. In time-course experiments, 82Se-enriched selenate and
      selenite were injected at doses of 50 and 10 microg/kg body weight, respectively,
      and the animals were sacrificed 5, 15, 30, 60 and 180 min later. It was suggested
      that selenate is directly taken up by the liver with an efficiency of
      approximately 1/2 compared with selenite, the latter being taken up by the liver
      after being metabolized to selenide in red blood cells. Although selenate and
      selenite were metabolized differently in the bloodstream, and also a part of only
      selenate was excreted directly into the urine, the 82Se taken up by the liver was
      shown to be metabolized in a manner indistinguishable between selenate and
      selenite. 82Se of selenite origin but not of selenate origin was suggested to
      undergo redox reaction in the bloodstream. These results suggest that although
      parenteral selenate is utilized less efficiently by the body, it is utilized in
      the liver in a similar manner to selenite much more safely.

PMID- 11522069
TI  - Selective and rapid liquid chromatography-mass spectrometry method for the
      quantification of rofecoxib in pharmacokinetic studies with humans.
AB  - An easy, rapid and selective method for the determination of rofecoxib in human
      plasma is presented. The analytical technique is based on reversed-phase high
      performance liquid chromatography coupled to atmospheric pressure chemical
      ionisation mass spectrometry (Finnigan Mat LCQ ion trap). The retention time of
      rofecoxib was 1.2 min. The method has been validated over a linear range from 1
      to 500 microg/l using celecoxib as internal standard. After validation, the
      method was used to study the pharmacokinetic profile of rofecoxib in 12 healthy
      volunteers after administration of a single oral dose (12.5 mg). The presented
      method was sufficient to cover more than 95% of the area under the curve. The
      pharmacokinetic characteristics (mean+/-SD) were tmax: 2.4+/-1.0 h, Cmax: 147+/
      34 microg/l, AUCinfinity: 2038+/-581 microg h/l and t 1/2: 11.3+/-2.1 h.

PMID- 11522070
TI  - Simple and rapid high-performance liquid chromatography method for the
      determination of ofloxacin concentrations in plasma and urine.
AB  - A high-performance liquid chromatographic method for the determination of
      ofloxacin in human plasma and urine was developed. The method involved
      deproteinisation of the sample with perchloric acid and analysis of the
      supernatant using a reversed-phase C18 column and fluorescence detection at an
      excitation wavelength of 290 nm and an emission wavelength of 460 nm. The assay
      was linear from 0.5 to 10.0 microg/ml. The relative standard deviation of intra-
      and inter-day assays was lower than 5%. The average recovery of ofloxacin from
      plasma was 93%. The method was evaluated in samples from healthy subjects whose
      drug levels were already measured by microbiological assay.

PMID- 11522072
TI  - Achilles tendon surgery and wound healing.

PMID- 11522071
TI  - Direct determination by high-performance liquid chromatography of sn-2
      monopalmitin after enzymatic lipase hydrolysis.
AB  - An alternative method to determine the sn-2 monopalmitin in infant formulas was
      developed and validated. This method offers many advantages over the traditional
      methods. It follows the official method in the first steps, purification of the
      fat or oil through an alumina column, and subsequently the triglycerides are
      incubated with pancreatic lipase in order to obtain the sn-2 monoglycerides. In
      traditional methods the sn-2 monoglycerides are separated by preparative thin
      layer chromatography and then, the 2-monoglycerides are converted into the
      corresponding fatty acid methyl esters and analysed by gas chromatography. In our
      method, separation, quantification and identification of the sn-2 monoglycerides
      were achieved by high-performance liquid chromatography with evaporative light
      scattering detection. The detection limit (0.19 microg), quantification limit
      (0.38 microg), linearity range (r=0.999, range 1-200 microg) and precision
      (SD=1.10) show the suitability of the proposed method. This method is faster,
      cheaper and simple and does not consume large quantities of reagents and
      materials.

PMID- 11522073
TI  - Single-incision technique misses the anatomical femoral anterior cruciate
      ligament insertion: a cadaver study.
AB  - We examined the arthroscopic appearance of the anterior cruciate ligament (ACL)
      attachment site on the femur in five fresh-frozen cadaver knees. First, the ACL
      was cut out, leaving a footprint of ligament-fibers with a length of 2 mm intact.
      The ACL was consistently found to insert on the lateral wall of the notch. No
      fibers were found to attach high in the roof of the notch at the 12 o'clock
      position. Secondly, we tried to reach the anatomical attachment site with a
      femoral aiming guide through a correctly placed tibial tunnel. This proved to be
      impossible. The closest position that could be reached was at the margin of the
      anatomical attachment site. Investigation of the distal femur after complete
      dissection confirmed these arthroscopic findings. Femoral aiming devices for use
      through the tibial tunnel aim for an isometric placement of the femoral tunnel,
      they do not aim for an anatomical position of the graft.

PMID- 11522074
TI  - A radiographic analysis of the relationship between the size and shape of the
      intercondylar notch and anterior cruciate ligament injury.
AB  - Notch-view radiographs were obtained from 108 persons with anterior cruciate
      ligament (ACL) injuries (55 women, 53 men) and 186 with intact ACL (94 women, 92
      men). Notch width, femur width, and notch width index were determined from each
      of the 294 radiographs. The notch was also categorized as either A-shaped or non
      A-shaped. Intrarater and interrater reliability ranged from 0.82 to 0.99 for
      notch width and femur width, respectively. Reliability within and between raters
      for the classification of notch shape ranged from 0.80 to 1.0. Notch width was
      significantly influenced by a 10 degree change in knee angle when repeated
      radiographs were taken. Femur width was not affected by knee angle across this
      range. Analysis revealed a higher proportion of A-shaped notches among women than
      men. However, notch shape was not related to injury status. Results showed a
      smaller notch width and notch width index in ACL-injured patients regardless of
      notch shape or gender. A-shaped notches were smaller than non-A-shaped notches
      regardless of injury status or gender. Both notch width and notch width index
      were found to be significant indicators of ACL injury. Knowledge of the shape of
      the notch added no useful information in differentiating patients based on injury
      status. Thus, regardless of gender, individuals who possess smaller notch
      dimensions appear to be at greater risk of injury than individuals with larger
      notches.

PMID- 11522075
TI  - Bone tunnel enlargement after anterior cruciate ligament reconstruction using
      hamstring tendons.
AB  - We retrospectively reviewed 87 anterior cruciate ligament reconstructions using
      autogenous hamstring tendons with the Endobutton technique to investigate the
      relationship between bone tunnel enlargement and clinical outcome and to identify
      factors that contribute to the enlargement. The clinical outcome was evaluated
      using the Lysholm score and KT-1000 arthrometer. The location of the femoral
      tunnel with respect to Blumensaat's line, the tibial tunnel with respect to the
      tibial plateau, and the angle between the femoral tunnel and Blumensaat's line
      (femoral tunnel angle) were measured. Bone tunnel enlargement was observed in 32
      patients (37%). Enlargement occurred in 22 of the femoral tunnels and 26 of the
      tibial tunnels. Enlargement of both tunnels occurred in 16 knees. There was no
      statistical difference in Lysholm scores or KT-1000 arthrometer measurements
      between the enlarged group and the unenlarged group. The femoral tunnel was
      placed more anteriorly in the enlarged femoral tunnel group than in the
      unenlarged femoral tunnel group. The tibial tunnel was placed more anteriorly in
      the enlarged tibial tunnel group than in the unenlarged tibial tunnel group. The
      femoral tunnel angle was significantly smaller in the enlarged femoral tunnel
      group than in the femoral unenlarged group. Gender, patient age, intraoperative
      isometricity, and graft size were not significant factors. Bone tunnel
      enlargement was not correlated with the clinical outcome measures. We conclude
      that the main factor associated with tunnel enlargement are the locations and
      angles of the tunnels. The windshield-wiper motion of the graft may be enhanced
      by changing tension in the graft due to tunnel malposition. An acute femoral
      tunnel angle may increase the mechanical stress on the anterior margin of the
      femoral tunnel.

PMID- 11522076
TI  - Atypical hamstrings electromyographic activity as a compensatory mechanism in
      anterior cruciate ligament deficiency.
AB  - Anterior cruciate ligament (ACL) deficiency may cause functional instability of
      the knee (noncopers), while other patients compensate and perform at the same
      level as before injury (copers). This pilot study investigated whether there is a
      compensatory electromyographic (EMG) activity of the hamstrings in copers,
      noncopers and control patients. Ten patients with an ACL deficiency were equally
      divided into two groups of copers and noncopers. All patients underwent gait
      analysis with EMG of six muscles around the knee. Ten healthy young men formed
      the control group. In contrast to noncopers, copers showed an atypical
      semitendinosus activity during stance phase; the corresponding trend was found in
      biceps femoris activity. There was no difference between copers and controls in
      knee extension during stance phase. The noncopers had less knee extension.
      Atypical hamstring muscle activity may thus be a compensatory mechanism by which
      copers enable themselves to perform on a normal level.

PMID- 11522077
TI  - Bilateral discoid medial menisci: association with bone changes in the tibia.
AB  - We present here the third case report of bilateral discoid medial menisci with
      associated bone changes. An 18-year-old man had bilateral medial tibial plateau
      depression (cupping) accompanying medial discoid menisci documented by magnetic
      resonance imaging and confirmed by arthroscopy. The patient was treated
      successfully by excision of the torn central anomalous discoid portion of the
      menisci using arthroscopic partial resection technique.

PMID- 11522078
TI  - Ultrasonography: an imaging modality enabling the diagnosis of bipartite patella.
AB  - Ultrasound was used to diagnose bipartite patella in seven adolescents with
      anterior knee pain, and the findings were compared to those from plain
      radiography and to those of a group of asymptomatic subjects. In all affected
      individuals the quadriceps and patellar tendons appeared normal on ultrasound.
      Sonographic examination of the patella demonstrated an irregularity of the bony
      contour with occurrence of a cleft between the main part of the patellar body and
      the large superolateral accessory ossicle. The signal detected in the interface
      between bones was less echogenic than bone reflecting its fibrocartilaginous
      nature. The correlation with conventional radiography was absolute, as was the
      inter- and intraobserver reliability. Ultrasound is thus proposed as a simple and
      reliable imaging modality in bipartite patella. We do not believe that it should
      replace the initial radiographic, but it can be used to evaluate the
      contralateral knee for bilaterality and as an adjunct to therapeutic procedures
      such as local injections to increase the accuracy of treatment.

PMID- 11522079
TI  - Bilateral peroneal nerve palsy after simultaneous bilateral total knee
      arthroplasty. Report of a case with rheumatoid arthritis.
AB  - In this study, we report on a 46-year-old female patient with bilateral severe
      gonarthrosis due to rheumatoid arthritis. Simultaneous bilateral cemented total
      knee arthroplasty was performed. Bilateral common peroneal nerve palsy was
      observed on the second postoperative day. The electromyographic diagnosis was
      "bilateral axonotmesis". Complete clinical and electromyographic motor recoveries
      were seen on both sides within 6 months postoperatively. The sensorial deficit
      was still present on one side at 2 years postoperatively. Preoperative severe
      flexion contracture and epidural anesthesia were assumed as the risk factors for
      the development of the nerve palsy in this patient.

PMID- 11522080
TI  - Tissue expansion for repair of severely complicated Achilles tendon ruptures.
AB  - We report on two patients with severely complicated Achilles tendon ruptures
      (ATR), including re-rupture, postoperative deep infection and subsequent tissue
      loss. Tissue expansion was used to facilitate tendon reconstruction and to ensure
      good healing potential with skin closure without tension. Tissue expansion is a
      valid option in patients with complicated ATR. The outcome for the two patients
      described here was good, with improved function and no major complications.

PMID- 11522081
TI  - Neovascularisation in Achilles tendons with painful tendinosis but not in normal
      tendons: an ultrasonographic investigation.
AB  - Chronic Achilles tendinosis is a condition with unknown aetiology and
      pathogenesis, most often, but not always, associated with painful nodular
      thickening of the tendon. In this investigation, 28 tendons (21 patients) with a
      painful nodule located at the 2-6 cm level in the tendon, and 20 normal (pain
      free) tendons, were examined with grey-scale ultrasonography combined with colour
      Doppler examination. In all tendons with a painful nodule, but not in any of the
      normal pain-free tendons, neovascularisation was seen in the area with tendon
      changes (localised widening of the tendon with focal hypo-echoic areas). In
      tendons with advanced changes, vessels were seen through the entire widened part
      of the tendons, and both arterial and venous blood flows were registered. The
      neovascularisation found in this investigation might have implications on the
      pathogenesis of chronic Achilles tendinosis.

PMID- 11522082
TI  - Stress fracture of the ulna in a professional tennis player using a double-handed
      backhand stroke.
AB  - Stress fractures of the ulna are uncommon injuries, but they have been reported
      in athletes from various sports. In tennis players stress fractures of the ulna
      are described exclusively in the nondominant forearm of athletes using a two
      handed backhand stroke. We report such a case in a 24-year-old tennis player,
      with special emphasis on diagnostic imaging, accurate grading of the injury, and
      specific treatment recommendations.

PMID- 11522083
TI  - The injury panorama in a Swedish professional ballet company.
AB  - We performed a combined retro- and prospective study of injuries in a Swedish
      professional, classical ballet company during 5 consecutive years. There were 390
      injuries incurred by 98 dancers over a 5-year period, i.e., 0.6 injuries/1000
      dance hours. Most injuries were considered to be due to overuse. The median sick
      leave was 2.3 weeks per injury. The foot and ankle region is vulnerable in
      classical ballet dancers, and overuse injuries can result in long periods of sick
      leave. Of the dancers employed for more than 1 year 95% were suffered injuries
      during the study period. We found considerable differences in the injury profile
      between male and female and between younger and older dancers. Male dancers
      suffered more frequently from acute injuries to the knee joint. Traumatic
      injuries were seen most frequently in male soloists. Female dancers more often
      suffered overuse injuries, especially to the foot and ankle region. The younger
      dancers more often suffered traumatic injuries, for example, ankle sprain, and
      also stress fractures.

PMID- 11522084
TI  - Effect of heparin on tendon degeneration: an experimental study on rats.
AB  - This study investigated the local effects of heparin on locally administered
      corticosteroid-induced experimental Achilles tendinitis. After performing
      Achilles degeneration, 28 rats were divided into two groups; one was treated with
      local heparin and the other with saline injections at 3 and 6-day intervals. The
      tendons and paratenons were excised after 60 or 75 days and evaluated
      histopathologically and statistically. Heparin-injected tendons and paratenons
      demonstrated significantly higher scores for most compared groups, thus worsening
      the degeneration. At the second part of the research, eight healthy tendons were
      injected with heparin at 3-day intervals for 1 month, and seven of them showed
      various degrees of degeneration. Heparin itself thus has a degenerative effect on
      the tendon and should not be used in the treatment of Achilles tendon
      degeneration.

PMID- 11522085
TI  - Autologous chondrocyte implantation: cells phenotype and proliferation analysis.
AB  - The phenotype and proliferation of human chondrocytes in culture were analyzed
      before they were implanted as autologous graft in cartilage lesions. During ten
      autologous chondrocyte implantations in articular cartilage lesions of the knee
      in ten patients, small amounts of cells to be implanted were collected and
      analyzed by morphology, cytochemistry (alcian blue, safranin-O), and
      immunocytochemistry (antibodies anti-S100 protein, anti-collagen types I and II,
      anti-chondroitin-S). In four cases the cells were also cultured for 3 weeks. At
      1, 10, and 20 days of culture cells were incubated with 1 microCi/ml
      [3H]thymidine for proliferation analysis. In all cases the cells showed the
      morphological appearance of mature chondrocytes, stained positively for alcian
      blue and safranin-O, and revealed a strong immunoreaction for S-100 protein, type
      II collagen, and chondroitin-S but not for type I collagen. Radioisotope assay of
      chondrocyte proliferation at 1, 10, and 20 days of culture revealed a progressive
      increase in [3H]thymidine incorporation. These findings indicate that the cells
      before autologous implantation maintain their differentiated phenotype of mature
      chondrocytes and proliferate greatly. This analysis is an essential step
      preceding wider use of this treatment in humans. However, other biological
      aspects of the autologous chondrocyte graft remain to be elucidated.

PMID- 11522086
TI  - Effect of recombinant human erythropoietin on adrenergic activity in normotensive
      hemodialysis patients.
AB  - Ten normotensive hemodialysis patients with severe anemia participated in the
      study. Human recombinant erythropoietin (rHuEpo) was administered i.v. 3 times a
      week in doses of 50 U/kg of body weight. During 12 weeks of observation, the mean
      hematocrit value increased from 19%, before start of therapy, to 32%.
      Simultaneous monitoring of serum plasma noradrenaline (NA) concentration showed
      an elevation from 202 to 281 pg/ml. An increase of NA concentration after a cold
      pressure stimulating test (CP) was not statistically significant after as
      compared to before treatment, but became statistically significant after 12 weeks
      of rHuEpo therapy (281 pg/ml before to 441 pg/ml after CP test, p < 0.01). The
      mean arterial blood pressure increased from 92 - 109 mmHg after 12 weeks of
      rHuEpo therapy (p < 0.001). We have demonstrated significantly increased NA blood
      concentrations after 12 weeks of rHuEPO therapy in normotensive patients, which
      correlated with increased MAP. This may suggest that the observed increase of
      noradrenaline concentration as a vasoactive substance after the CP test may
      contribute to hypertension during rHuEPO therapy.

PMID- 11522087
TI  - Influence of Bsml vitamin D receptor gene polymorphism on the response to a
      single bolus of calcitrol in hemodialysis patients.
AB  - AIMS: BsmI polymorphism of the vitamin D receptor gene has been linked to
      hyperparathyroidism severity and calcitriol levels. The aim of this study was to
      analyze the response to a single bolus of calcitriol in hemodialysis patients
      with the BB and bb genotype. PATIENTS: Twenty homozygous BsmI hemodialysis
      patients (9 BB and 11 bb). METHODS: Hyperparathyroidism was assessed comparing
      basal PTH levels, and in 17 patients, also measuring the inhibition with
      hypercalcemia. Patients were given a bolus of calcitriol and PTH in absolute
      terms and in percentages relative to the baseline values at 24, 48 and 72 hours
      after the bolus were measured. All biochemical parameters were compared between
      genotypes with univariant ANOVA and additionally, PTH relative values were
      compared with general factorial analysis of variance, adjusting for calcium and
      phosphorus. Means were also compared within each genotype between consecutive
      determinations with non-parametric Wilcoxon analysis, using each patient as
      his/her own control. The response to calcitriol was also assessed by the area
      under the curve for each patient and was subsequently compared between genotypes.
      RESULTS: There were no differences on hyperparathyroidism severity between the
      groups. The BB genotype showed a better response than bb to calcitriol 72 hours
      after the bolus (percentage relative to basal PTH value: BB: 63%, bb: 88.6%, p =
      0.03; BB vs bb with univariant ANOVA). When general factorial analysis of
      variance was applied, adjusting for serum calcium and phosphorus, genotype showed
      a significant influence on the response to calcitriol at 72 hours (p = 0.04).
      When each patient was used as his/her own control, the BB genotype showed a
      significant decrease in PTH levels at 48 and 72 hours (p = 0.00 baseline vs 48 h,
      and p = 0.01 baseline vs 72h) whereas the bb did not. CONCLUSIONS: BsmI
      polymorphism of the VDR gene induces differences on the response to a single
      bolus of calcitriol independently of calcium and phosphorus.

PMID- 11522088
TI  - Profiling hemodialysis patients with high ferritin levels.
AB  - AIMS: Hemodialysis patients receiving intravenous iron and erythropoietin may
      develop greatly elevated ferritin levels. Both iron overload and inflammation may
      account for this hyperferritinemia. The aim of this study was to try to identify
      the cause of the high ferritin level among individual patients. METHODS: Sixty
      seven chronic hemodialysis patients with ferritn levels < 700 microg/l were
      compared to 47 patients whose ferritin levels were > or = 700 microg/l. Clinical
      and laboratory data were collected and evaluated by cluster analysis which
      allowed patients to be placed into statistically dissimilar groups. RESULTS: The
      47 high ferritin patients segregated into 3 clusters consisting of 28, 3, and 16
      patients based on ferritin, zinc protoporphyrin, albumin, C-reactive protein, and
      hemoglobin. When contrasted with cluster 1, cluster 3 patients had higher levels
      of Zn-PP, CRP, and ferritin and lower levels of albumin and hemoglobin.
      CONCLUSIONS: Utilizing these data and the results of many other studies, we
      conclude that, relative to cluster 1, cluster 3 patients had a more intense
      inflammatory response that blocked iron mobilization required for erythrocyte
      production. Cluster analysis appears to be a useful method of analyzing clinical
      data of relatively small patient population.

PMID- 11522089
TI  - Etiology of bacterial septicemia in chronic dialysis patients in the United
      States.
AB  - AIMS: Previous studies have identified risk factors for and mortality associated
      with hospitalized septicemia (septicemia) in patients with end-stage renal
      disease (ESRD). However, the etiologies of septicemia in this population have not
      been determined. METHODS: 327,993 patients in the United States Renal Data System
      initiated on ESRD therapy between January 1, 1992, and June 30, 1997, who never
      received renal transplants were analyzed in a retrospective registry study of
      hospitalized cases of septicemia (ICD9 038.x). RESULTS: Of the study population,
      43,441 (13.2%) had septicemia. In logistic regression analysis, septicemia was
      associated with female gender, African American race, ESRD due to diabetes and
      obstruction/chronic pyelonephritis, increased age, and hemodialysis (vs.
      peritoneal dialysis). Polycystic kidney disease and glomerulonephritis were
      associated with decreased risk of septicemia. At initiation of dialysis, higher
      hemoglobin, and lower weight, creatinine, and albumin were associated with
      septicemia. Among patients with septicemia, the leading specified etiologies were
      Staphylococcus (34%) and miscellaneous Gram-negative rods (21.7%). Etiologies of
      septicemia were significantly associated with hemodialysis (Gram-positives and
      Pneumococcus), female gender (Gram-negatives except Pseudomonas), African
      American race (Staphylococcus), and diabetes (global). Hemodialysis (vs.
      peritoneal dialysis) and Staphylococcus as an etiology of septicemia were
      associated with repeated hospitalizations for septicemia. Septicemia was
      independently associated with patient mortality, and African Americans and
      females with septicemia were at disproportionately greater risk of mortality.
      CONCLUSIONS: This study identifies significant associations between septicemia
      and female gender, African American race, hemodialysis, and higher hemoglobin.
      Significant associations between etiologies of septicemia and patient subgroups
      are also identified.

PMID- 11522090
TI  - Hyperhomocysteinemia, diabetes mellitus, and carotid atherosclerosis
      independently increase atherosclerotic vascular disease outcome in Japanese
      patients with end-stage renal disease.
AB  - BACKGROUND: Patients with end-stage renal disease (ESRD) have high mortality from
      atherosclerotic/atherothrombotic vascular disease (AVD). However, the role of an
      elevated plasma total homocysteine (tHcy) level as a risk factor is uncertain in
      ESRD. METHODS: We enrolled 55 ESRD patients in a prospective follow-up study in
      order to evaluate the prognostic significance of their tHcy levels, common
      methylenetetrahydrofolate reductase (MTHFR) gene polymorphism, and other
      atherosclerotic risk factors, in combination with the results of B mode
      ultrasound for carotid arteries. RESULTS: Mean intima-media thickness of the
      common carotid artery (CCA-IMT) in ESRD patients was thicker than that in 102 age
      and sex-matched healthy controls. Carotid plaque was more frequently present in
      patients compared with controls, as was calcified plaque more common in patients
      (p < 0.001). Plasma tHcy levels (mean +/- SD) in patients (39.1 +/- 27.2 nmol/ml)
      were higher than that (8.8 +/- 2.7 nmol/ml) in controls (p < 0.001). Folic acid
      was the major determinant of elevated tHcy levels in ESRD patients. During the
      follow-up period of 31 +/- 3 months, 14 patients had one or more AVD
      complications, and 10 consequently died from AVD causes. Proportional hazards
      modeling showed that 5-year intervals of age (relative risk of 2.95, 95% CI 1.62 
      5.37), 10 nmol/ml intervals of tHcy levels (relative risk of 2.31, 95% CI 1.31 -
      4.08), and presence of diabetes mellitus (relative risk of 6.62, 95% CI 1.07 +/-
      40.8) were independent predictors of future AVD events, and tHcy levels (relative
      risk of 2.67, 95% CI 1.29 - 5.52) and age (relative risk of 2.10, 95% CI 1.15 -
      3.83) were those of AVD mortality. We also found a significant association
      between carotid plaque prevalence and AVD events (X(2) = 11.6, p = 0.001).
      CONCLUSION: Hyperhomocysteinemia, diabetes mellitus, and carotid atherosclerosis
      appeared to contribute independently to increase the risk of AVD outcome in
      Japanese patients with ESRD.

PMID- 11522091
TI  - Usefulness of long axis M-mode echocardiographic measurements for optimum
      dialysis in patients on maintenance hemodialysis: comparison with changes in
      plasma levels of atrial natriuretic peptide and brain natriuretic peptide.
AB  - It has been suggested that analyzing the left ventricular long axis motion can
      result in the sensitive detection of cardiac functional disorders. AIM: To
      evaluate the usefulness of left ventricular long axis indices in managing
      patients on maintenance hemodialysis. METHODS: Eighteen hemodialysis patients
      (mean age 51 +/- 10 years) as well as 16 healthy persons (mean age 49 +/- 9
      years) were examined. Echocardiograms were recorded, and the plasma
      concentrations of atrial natriuretic peptide (ANP) and brain natriuretic peptide
      (BNP) were measured before and after a session of hemodialysis. The following
      parameters were measured: the left atrial diameter (LAD) and end-diastolic left
      ventricular diameter (LVDd) from M-mode echocardiograms, the end-diastolic LV
      volume (LVEDV) and ejection fraction (EF) from 2-D echocardiography, the E/A
      ratio from transmitral Doppler, the atrial systolic excursion of long axis motion
      of the mitral ring (ALAM) and maximal lengthening rate of the mitral ring toward
      the left atrium during the early diastolic phase (MLRe) from LV long axis M-mode
      echocardiograms. RESULTS: LAD, LVDd, LVEDV, and ALAM showed a positive
      correlation with plasma levels of ANP and BNP. EF, the E/A ratio, and MLRe showed
      a negative correlation with plasma levels of ANP and BNP. Changes in ALAM and
      plasma levels of ANP during hemodialysis were larger in the subgroup of ALAM < or
      = 0.55 cm before hemodialysis than in the subgroup of ALAM < 0.55 cm before
      hemodialysis. CONCLUSION: These results indicate that the left ventricular long
      axis index can detect a disorder of left ventricular diastolic function, and that
      a hemodialysis patient whose ALAM before hemodialysis is < 0.55 cm is dialyzed
      with good volume control conditions.

PMID- 11522092
TI  - The initial attitudes of patients toward longer maintenance hemodialysis.
AB  - Longer hemodialysis (HD) as practiced in parts of Europe and Japan may improve
      both blood pressure control and patient survival. Nevertheless, in the USA, the
      trend has been to shorten dialysis time using larger dialyzers and increased
      blood flows. Many patients find the notion of shorter dialysis enticing. Most are
      unaware ofthe potential benefits of longer dialysis. We surveyed stable chronic
      HD patients in an urban area, the vast majority of whom received conventional 4
      hour treatments, regarding their attitude toward extending their dialysis time to
      5 hours. They were informed that longer dialysis has been associated with better
      blood pressure control and improved survival. One hundred and sixteen patients
      completed questionnaires during a single dialysis session. Forty-six (40%) agreed
      to extended dialysis while 70 (60%) did not. There was no difference between the
      groups with respect to the following variables: age, race, etiology of ESRD, time
      on dialysis, marital status, number of children at home, number residing in the
      household, education, or employment status. Male gender was associated with a
      positive response (p = 0.03). Various suggested and spontaneous reasons were
      given for a negative response. CONCLUSION: With minimally detailed information, 4
      in 10 patients were willing to extend their treatment time to 5 hours in the hope
      of improving morbidity and survival. No sociodemographic variable except gender
      was associated with a positive response.

PMID- 11522093
TI  - Familial hypomagnesemia-hypercalciuria in 2 siblings.
AB  - Familial hypomagnesemia-hypercalciuria with nephrocalcinosis and renal
      insufficiency in childhood is a rarely described disease. Two siblings of
      consanguineous Tunesian parents (first cousins), a 2-year-old boy and a 4-year
      old girl presented with renal insufficiency and severe bilateral
      nephrocalcinosis. Both were found to have decreased serum and intracellular
      magnesium concentrations, increased urinary excretion of magnesium and calcium,
      mild glomerular and severe tubular proteinuria and low citrate excretion in
      urine. Pathological biochemical findings and the severity of nephrocalcinosis of
      the boy compared to findings of the sister were strongly marked, Histology of the
      boy's kidney showed severe medullary nephrocalcinosis, tubular atrophy, focal
      lymphoplasmacellulary infiltration, focal cortical fibrosis, immature glomerula,
      segmental and global glomerulosclerosis. Subsequent mutation analysis revealed a
      homozygous frameshift mutation in the gene paracellin-1 in both affected
      individuals. Therapy consisted of sodium bicarbonate, cholecalciferol,
      calcitriol, hydrochlorothiazide, citrate salts and oral magnesium administration.
      Hypercalciuria decreased in both children by therapy with thiazide diuretics, but
      hypomagnesemia was unresponsive to magnesium administration. After a 32-month
      follow-up the boy commenced hemodialysis at the age of 5 years, whereas his
      sister showed no decline in renal function.

PMID- 11522094
TI  - Use of midodrine (Gutron) to treat permanent hypotension in a chronic
      hemodialysis patient.
AB  - Chronic hypotension, infrequent though possible in chronic renal failure patients
      on hemodialysis, has harmful consequences on their physical state and hence
      general well-being. These patients often experience acute intradialytic
      manifestations while non-pharmacologic interventions as pharmacologic agents are
      sometimes insufficient to improve symptoms. Well tolerated, midodrine appears to
      be a suitable and effective agent as it raises blood pressure significantly via
      its effect on peripheral alpha-adrenergic receptors. The authors describe their
      use of midodrine in a dialysis patient for the longest period of time reported up
      to now, documented by a pharmacokinetic study, confirming long-term both clinical
      efficacy and safety of the drug.

PMID- 11522095
TI  - Renal abscess: recovery without hospitalization and drainage.
AB  - BACKGROUND: Renal absceeses in childhood are rare and require hospitalization,
      antibiotic therapy and drainage. PATIENTS: Two cases of renal abscess in
      childhood are described. In both cases there was no history of either antecedent
      skin infection or urinary tract infection or reflux. Flank pain and fever had a
      sudden onset. RESULTS: The diagnosis was made in the first case by ultrasound and
      gadolinium-enhnaced magnetic resonance, in the second case ultrasound and
      computerized axial tomography were used. The patients were successfully treated
      at home with antibiotic therapy but without drainage. CONCLUSION: Renal abscesses
      must be suspected in children with loin pain, fever and leukocytosis. They may
      heal even without  hospitalization and drainage.

PMID- 11522096
TI  - Acute renal failure in a patient with paroxysmal nocturnal hemoglobinuria.
AB  - Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired disorder characterized
      by low-grade, chronic hemolytic anemia accompanied by either thrombocytopenia or
      leucopenia. Kidney involvement is usually benign and secondary to chronic tubular
      deposition of hemosiderin. Acute renal failure may occur in association with a
      hemolytic crisis. We report the case of a 70-year-old Caucasian woman with PNH
      who developed reversible acute renal failure requiring hemodialysis following a
      gastointestinal illness. Renal biopsy demonstrated acute tubular necrosis with
      considerable hemosiderin deposition, but no evidence of vascular thrombosis.

PMID- 11522097
TI  - Septic myositis in a chronic dialysis patient.

PMID- 11522098
TI  - Blood pressure and melatonin in chronic renal failure.

PMID- 11522099
TI  - RPA position on optimal length of observation after percutaneous renal biopsy.

PMID- 11522100
TI  - Effects of angiotensin-converting enzyme inhibitor and steroid therapy on
      proteinuria in FSGS: a retrospective study in a single clinic.
AB  - We retrospectively evaluated the response to steroids (S) +/- angioten-sin
      converting enzyme inhibitors (ACEI) vs. ACEI in nephrotic patients with FSGS seen
      in our clinic from 1992 - 1999. Of 48 patients with biopsy-proven FSGS, 30 had
      pre-therapy and follow-up evaluations of proteinuria. Of these, 22 were nephrotic
      (> or = 3 g protein/24 h). Twelve/22 were treated with S and 10/22 with ACEI +/-
      HMG-CoA reductase inhibitor (statin) alone. 92% of S patients received ACEI
      during follow-up, 83% concurrently with steroid treatment. The two cohorts (S vs.
      ACEI) were not different in age (34 +/- 12 vs. 33 +/- 12), sex (75% vs. 78%
      male), or ethnicity (83% vs. 83% African American). Mean follow-up time was 16
      (range 4 - 61 months) vs. 23 months (range 6 - 56 months). Mean S dose was 70 mg
      qd (range 60 - 100 mg), with mean treatment duration of 4 months. Nephrotic
      patients were compared with regard to degree of proteinuria at follow-up. There
      were no complete remissions (proteinuria < or = 200 mg/24 h) in either group.
      There was no difference in partial remissions (> 200 mg to < 3 g proteinuria/24
      h) between the two groups - 5/12 vs. 6/10 (p = 0.434). There was no difference in
      the proportion of patients progressing to ESRD. Although proteinuria decreased
      significantly with time in both groups, there was no significant treatment
      effect. There was no significant time or treatment effect on serum creatinine.
      Mean arterial pressure and serum cholesterol were not significantly different
      between the groups. Thus, treatment with S +/- ACEI is no more effective in
      reducing proteinuria in FSGS than treatment with ACEI alone.

PMID- 11522101
TI  - Angiotensin-converting enzyme inhibitors and probucol suppress the time-dependent
      increase in urinary Type IV collagen excretion of Type II diabetes mellitus
      patients with early diabetic nephropathy.
AB  - BACKGROUND: A multicenter prospective clinical trial was carried out in 9
      National Hospitals in Japan to elucidate the time-dependent change in urinary
      Type IV collagen excretion rate of Type II diabetes mellitus (DM) patients, and
      to investigate whether an angiotensin-converting enzyme inhibitor (ACE-I) or
      probucol is effective in preventing progression of renal involvement of diabetics
      by evaluating urinary Type IV collagen excretion. METHODS: Normo- and
      microalbuminuric patients with Type II DM were recruited. Patients were assigned
      to either the control (n = 88), ACE-I (n = 43) or probucol (n = 37) group and
      treated for 24 months. Besides albumin excretion rate (AER), urinary Type IV
      collagen excretion rate was also measured. RESULTS: Although, AER, urinary N
      acetyl-beta-D-glucosaminidase and beta2-microglobulin excretion rates in the
      control group did not vary over 24 months, urinary Type IV collagen excretion
      rate in the control group increased time-dependently (p < 0.01 vs baseline at 18
      months and p < 0.005 vs baseline at 24 months). In the ACE-I and probucol groups,
      time-dependent increases in urinary Type IV collagen excretion rates were not
      observed. In the ACE-I group, the urinary Type IV collagen excretion rate was
      significantly lower than that in the control group at 24 months (p < 0.05). In
      the probucol group, the urinary Type IV collagen excretion rate was significantly
      lower than that in the control group at 6 months (p < 0.05). In the ACE-I group,
      AER decreased significantly compared with baseline at 18 months (p < 0.05) and at
      24 months (p < 0.005). CONCLUSIONS: ACE-I has a beneficial effect and probucol
      may have a beneficial effect in preventing the progression of early diabetic
      nephropathy. Measurement of the urinary Type IV collagen excretion rate in
      combination with AER would be useful for the management of early renal
      involvement in Type II DM.

PMID- 11522103
TI  - Models for combining random and systematic errors. assumptions and consequences
      for different models.
AB  - A series of models for handling and combining systematic and random
      variations/errors are investigated in order to characterize the different models
      according to their purpose, their application, and discuss their flaws with
      regard to their assumptions. The following models are considered 1. linear model,
      where the random and systematic elements are combined according to a linear
      concept (TE = absolute value(bias) + z x sigma), where TE is total error, bias is
      the systematic error component, sigma is the random error component (standard
      deviation or coefficient of variation) and z is the probability factor; 2.
      squared model with two sub-models of which one is the classical statistical
      variance model and the other is the GUM (Guide to Uncertainty in Measurements)
      model for estimating uncertainty of a measurement; 3. combined model developed
      for the estimation of analytical quality specifications according to the clinical
      consequences (clinical outcome) of errors. The consequences of these models are
      investigated by calculation of the functions of transformation of bias into
      imprecision according to the assumptions and model calculations. As expected, the
      functions turn out to be rather different with considerable consequences for
      these types of transformations. It is concluded that there are at least three
      models for combining systematic and random variation/errors, each created for its
      own specific purpose, with its own assumptions and resulting in considerably
      different results. These models should be used according to their purposes.

PMID- 11522102
TI  - The impact of cardiac natriuretic peptide determination on the diagnosis and
      management of heart failure.
AB  - The long-predicted endocrine function of the heart has been proven by the
      discovery of atrial natriuretic peptide (atrial natriuretic factor, A-type
      natriuretic peptide; ANP) 20 years ago. This subsequently led to the description
      of a whole family of structurally similar but genetically distinct peptides, the
      natriuretic peptide family, which contributes to cardiovascular homeostasis.
      These looped peptides promote natriuresis and diuresis, act as vasodilators, and
      exert antimitogenic effects on cardiovascular tissues. Two members, ANP and brain
      natriuretic peptide (B-type natriuretic peptide; BNP) are secreted by the heart
      mainly in response to myocardial stretch induced by volume load. The natriuretic
      peptides are synthesized as preprohormones. The C-terminal endocrinological
      active peptides (ANP, BNP) and their N-terminal prohormone fragments are found in
      plasma. The natriuretic peptide system is activated to its highest degree in
      ventricular dysfunction. However, natriuretic peptides are increased in all
      patients with edematous disorders which lead to an increase in atrial tension or
      central blood volume, such as renal failure or ascitic liver cirrhosis. It could
      be demonstrated that in chronic heart failure patients and during the subacute
      phase of myocardial infarction, of all tested neurohormones, the cardiac
      natriuretic peptides were best markers to identify heart failure and the most
      powerful predictors of morbidity and mortality. Natriuretic peptides are
      independent markers for risk assessment. In comparative studies BNP was superior
      to ANP and its N-terminal prohormone fragments in myocardial infarction as well
      as in chronic heart failure patients. Less data on N-terminal proBNP (NT-proBNP)
      is available, but BNP and NT-proBNP appear to be equivalent markers. For primary
      care physicians natriuretic peptide measurement is useful to decide which patient
      with suspected heart failure warrants further investigation, particularly when
      assessment of left ventricular function is not readily available. Natriuretic
      peptides have an excellent negative predictive value, particularly in high risk
      patients. An increase in BNP is serious enough to warrant follow-up examinations.
      For the cardiologists the natriuretic peptides are helpful for guidance of
      therapy and monitoring disease course in heart failure patients and for risk
      stratification in heart failure and myocardial infarction.

PMID- 11522104
TI  - Nucleosomes in serum as a marker for cell death.
AB  - The concentration of nucleosomes is elevated in blood of patients with diseases
      which are associated with enhanced cell death. In order to detect these
      circulating nucleosomes, we used the Cell Death Detection-ELISAplus (CDDE) from
      Roche Diagnostics (Mannheim, Germany) (details at http:??biochem.roche.com). For
      its application in liquid materials we performed various modifications: we
      introduced a standard curve with nucleosome-rich material, which enabled direct
      quantification and improved comparability of the values within (CVintraassay:3.0
      4.11%) and between several runs (CVinterassay:8.6-13.5%), and tested the
      analytical specificity of the ELISA. Because of the fast elimination of
      nucleosomes from circulation and their limited stability, we compared plasma and
      serum matrix and investigated in detail the pre-analytical handling of serum
      samples which can considerably influence the test results. Careless venipuncture
      producing hemolysis, delayed centrifugation and bacterial contamination of the
      blood samples led to false-positive results; delayed stabilization with EDTA and
      insufficient storage conditions resulted in false-negative values. At
      temperatures of -20 degrees C, serum samples which were treated with 10 mM EDTA
      were stable for at least 6 months. In order to avoid possible interfering
      factors, we recommend a schedule for the pre-analytical handling of the samples.
      As the first stage, the possible clinical application was investigated in the
      sera of 310 persons. Patients with solid tumors (n=220; mean=361 Arbitrary Units
      (AU)) had considerably higher values than healthy persons (n=50; mean=30 AU;
      p=0.0001) and patients with inflammatory diseases (n=40; mean= 296 AU; p=0.096).
      Within the group of patients with tumors, those in advanced stages (UICC 4)
      showed significantly higher values than those in early stages (UICC 1-3)
      (p=0.0004).

PMID- 11522105
TI  - Comparative nuclear magnetic resonance studies of water permeability of red blood
      cells from maternal venous blood and newborn umbilical cord blood.
AB  - Comparative morphological and nuclear magnetic resonance (NMR) measurements of
      the diffusional permeability (Pd) were performed on red blood cells (RBCs) from
      maternal venous blood and fetal RBCs, isolated from cord blood taken at delivery.
      Fetal RBC had a diameter of 8.79+/-0.03 microm (mean+/-standard deviation, SD), a
      volume of 103 microm3 and a surface area of 157 microm2. We report here the first
      comparative measurements of Pd of maternal and fetal RBCs by using a Mn2+-doping
      NMR technique. The values of Pd were, in the case of maternal RBC, 3.7 x 10(-3)
      cm/s at 15 degrees C, 4.1 x 10(-3) cm/s at 10 degrees C, 4.9 x 10(-3) cm/s at 25
      degrees C, 5.2 x 10(-3) cm/s at 30 degrees C and 7.2 x 10(-3) cm/s at 37 degrees
      C. For fetal RBC all corresponding Pd values were almost half, namely 2.0 x 10(
      3) cm/s at 15 degrees C, 2.3 x 10(-3) cm/s at 20 degrees C, 2.8 x 10(-3) cm/s at
      25 degrees C, 3.4 x 10(-3) cm/s at 30 degrees C and 4.4 x 10(-3) cm/s at 37
      degrees C. The decreased Pd values of fetal RBCs were probably due to lower
      channel-mediated water permeability compared with adult RBCs. The values of the
      activation energy for water permeability (E(a,d)) were significantly higher for
      fetal RBCs (27.6+/-5.0 kJ/mol) than for adult RBCs (22.8+/-2.7 kJ/mol). A
      positive correlation between the Pd values of the two kinds of RBCs was found.
      This points to the genetic basis for the determination of RBC water permeability.

PMID- 11522106
TI  - Optimization of single-stranded conformation polymorphism (SSCP) analysis for
      screening for the estrogen receptor-alpha gene polymorphism P325P.
AB  - Since there are no theoretical models for single-stranded conformation
      polymorphism (SSCP) analysis, conditions for detecting specific mutation must be
      found experimentally. Previously, a time-consuming (22 hours) SSCP method was
      used for the detection of polymorphism in codon 325 (CCC to CCG; P325P) in exon 4
      of estrogen receptor-alpha gene. The aim of our work was to study different gel
      loading buffers, additives to polyacrylamide gel, voltages, running times and
      temperatures of electrophoresis, in order to develop a better and faster SSCP
      analysis for screening of P325P polymorphism. Our results show that a low ionic
      strength gel loading buffer and 10% addition of glycerol to the 8% polyacrylamide
      gel (37:1) are essential for the good separation of mutated and wild-type single
      stranded conformers of exon 4. The most suitable conditions for electrophoresis
      were 300 V, 5 h and 22 degrees C. We concluded that a much faster SSCP analysis
      for sreening of P325P polymorphism of estrogen receptor-alpha gene was developed.
      Although our final result could be applied only to the detection of the described
      genetic polymorphism, we hope that the results of our study will be helpful to
      analysts using SSCP analysis in their mutation screening programs.

PMID- 11522107
TI  - Serum total renin after tubal sterilization.
AB  - The effect of laparoscopic tubal sterilization by Hulka or Filshie clips on serum
      total renin levels was evaluated in 33 healthy, regularly menstruating women.
      Serum total renin levels were measured in the follicular (days 3 to 7) and in the
      luteal (days 20 to 24) phase during the cycle immediately preceeding the
      sterilization and 12 months after the procedure. The total renin secreted did not
      change after the sterilization. The follicular phase levels were lower (160 +/-
      113 and 170 +/- 93 ng/l, respectively) than luteal phase levels (230 +/- 124 and
      228 +/- 83 ng/l, respectively) in both cycles studied (p=0.0001 for both). The
      length of the menstrual cycle was not affected, either. Laparoscopic tubal
      sterilization caused no measurable changes in total renin secretion during one
      year follow-up.

PMID- 11522108
TI  - Oxidative stress and male IGF-1, gonadotropin and related hormones in diabetic
      patients.
AB  - Elevation of glucose concentration in diabetes may induce generation of oxygen
      free radicals such as superoxide (O2*-) and hydroxyl (*OH). The aim of the
      present study was to investigate the effect of the oxidative stress on the
      activities of blood superoxide dismutase (SOD), catalase (CAT), glutathione
      peroxidase (GSH-Px), glutathione reductase (GSSG-R) and aldose reductase, the
      levels of reduced glutathione (GSH), lipid peroxidation (thiobarbituric acid
      reactive substances; TBARS) and plasma levels of insulin-like growth factor-1
      (IGF-1), follicle-stimulating hormone (FSH), luteinizing hormone (LH) and
      testosterone in type 2 (non-insulin-dependent diabetes) patients and in healthy
      controls. Blood SOD, CAT, GSH-Px and GSSG-R were lower in type 2 diabetic
      patients compared with the the control group. Blood aldose reductase activity was
      elevated in patients with type 2 diabetes compared with the control group. GSH
      was decreased while TBARS concentration was increased in red blood cells (RBC)
      and leukocytes from the patients with type 2 diabetes mellitus in comparison to
      the control group. The mean values of plasma LH, FSH and testosterone were
      decreased, whereas the mean plasma IGF-1 concentration was increased in type 2
      diabetes compared with controls. These findings support the hypothesis that
      hyperglycemia enhances the activity of the polyol pathway and impairs the
      antioxidant status, particularly glutathione redox cycle, resulting in poorer
      defense against oxidative stress. In addition, decreased circulating testosterone
      and gonadotropin levels may reflect the oxidative stress exerted by diabetes.

PMID- 11522109
TI  - New PCR-based method for the Sp1 site polymorphism in the COL1A1 gene.
AB  - Polymorphism in the Sp1 binding site in the first intron of the COL1A1 gene has
      been related to increased risk of osteoporosis in several populations. To
      overcome the difficulties associated with the use of mismatch oligonucleotide
      primers in the original method for its detection, we developed a procedure
      involving PCR amplification of a 598-base pair sequence from the intron and its
      digestion with the restriction enzyme Van 91 I. The more frequent allele is
      recognized by the enzyme, whereas the reaction is abolished in the less frequent
      allele. Two convenience samples from the population in northern Finland,
      consisting altogether of 173 individuals, were studied. The overall frequencies
      were 0.864 for the G and 0.136 for the T allele, with a heterozygocity of 27.2%.
      The frequency of the T allele is towards the lower end of the range observed for
      other European populations.

PMID- 11522110
TI  - Comparability of serum and plasma concentrations of haemostasis activation
      markers.
AB  - Since serum and plasma D-dimer concentrations correlate very well, we evaluated
      the comparability of other haemostasis activation markers in plasma and serum.
      Prothrombin fragment F1+2, fibrin monomer and D-dimer concentrations were
      measured with commercially available immunoassays in serum and plasma. Serum to
      plasma ratios were evaluated to determine the direct (prothrombin fragment F1+2)
      and indirect (fibrin monomer, D-dimer) downstream influence of prothrombinase on
      the serum to plasma comparability. Prothrombin fragment F1+2 serum and plasma
      concentrations did not correlate (R2 = 0.09, ns), while an unexpected high degree
      of correlation was found for fibrin monomer (R2 = 0.66, p < 0.001), and, as
      expected, a very good correlation was found for D-dimer (R2 = 0.94, p < 0.001).
      Median serum to plasma ratios decreased from prothrombin fragment F1+2 (16.26) to
      fibrin monomer (2.24, p < 0.001) and D-dimer (1.00, p < 0.001), following a
      highly linear relationship (R2 = 0.93) Plasma and serum concentrations of the
      evaluated markers correlate the better the farther from prothrombinase activity
      the respective marker is generated. Serum is not suitable for prothrombin
      fragment F1+2 measurements, whereas fibrin monomer serum concentrations seem of
      value for research applications. With the used assay, serum seems an appropriate
      matrix for clinical D-dimer measurements. This would considerably simplify
      testing strategies. Validation in further clinical trials is needed.

PMID- 11522111
TI  - Importance of validation of immunoassays for intact proinsulin.
AB  - The aim of this study was to compare results obtained from two commercially
      available immunoassay kits for intact proinsulin. Fasting and post-prandial
      samples were obtained from both healthy subjects and patients with type 2
      diabetes mellitus and assays were carried out according to the manufacturers'
      instructions. Coefficient of variation of the duplicates in both assays was
      acceptable with the MLT Intact Proinsulin assay giving slightly better overall
      precision. Regression analysis indicated a good correlation between the assays
      (r=0.97), however, a procedure better designed to compare analytical methods
      demonstrated a considerable lack of agreement for some samples. Dilution of
      samples in the Dako assay greatly affected the results when compared to samples
      assayed undiluted, whereas in the MLT assay, dilution of samples produced the
      expected results. Repeat comparison, assaying samples neat in the MLT assay and
      diluted 1:5 in the Dako assay, resulted in a considerable improvement in the
      agreement between the Dako and MLT assays. This study underlines the importance
      of the use of validation procedures which demonstrate quantitative analytical
      recoveries from a variety of specimens over the working range of the assay method
      in question.

PMID- 11522113
TI  - Menopause, coronary artery disease and antioxidants.
AB  - The aim of this study was to examine the influence of menopause on the activity
      of primary intracellular antioxidant enzymes, superoxide dismutase (SOD),
      glutathione peroxidase (GPx) as well as on the level of total antioxidant status
      (TAS) in healthy women and women with coronary artery disease (CAD). We studied
      140 women divided into two groups. The first group (controls) consisted of 99
      healthy women aged between 18 and 55 years) classified into three subgroups: pre
      menopausal women (Pre-M; n=48), peri-menopausal women (Peri-M; n=22) and post
      menopausal women (Post-M; n=29). The second group consisted of 41 women with CAD
      aged between 48-68 years, classified into two subgroups: Peri-M (n=20) and Post-M
      (n=21). The activity of GPx and the level of TAS were significantly decreased in
      Peri-M (p<0.005) and Post-M groups (p<0.001) in comparison with the Pre-M group.
      SOD was decreased in Peri-M and Post-M groups compared with the Pre-M group, but
      this was statistically not significant. The activity of SOD and GPx as well as
      TAS were significantly decreased in the Post-M group compared with the Peri-M
      group with CAD (p<0.001). The activity of the antioxidant enzymes in Peri-M and
      Post-M groups was significantly decreased (p<0.02) in comparison with the control
      group. TAS was not changed in women with CAD in comparison with controls. In
      conclusion, menopause leads to the reduction of the level of antioxidants,
      especially in women with CAD.

PMID- 11522112
TI  - Plant sterol-enriched margarine lowers plasma LDL in hyperlipidemic subjects with
      low cholesterol intake: effect of fibrate treatment.
AB  - Phytosterols, found in fat-soluble fractions of plants, chemically resemble
      cholesterol and inhibit cholesterol absorption in the small intestine.
      Phytosterol consumption in human subjects reduces plasma total and low density
      lipoprotein-cholesterol (LDL-C) levels. The primary aim of this study was to
      determine the efficacy of a low-fat spread enriched with plant sterols in
      reducing total and LDL-C concentrations in primary hypercholesterolemia. The
      secondary objective was to evaluate whether patients receiving a lipid-lowering
      drug (fibrate) might differ in their response to plant sterols. The study was a
      randomized, double-blind, placebo-controlled two-period cross-over trial with two
      treatments and three periods. Both treatment periods lasted 2 months, with a
      washout period (2 months) between them. Spread enriched with plant sterols was
      compared to non-enriched control spread. Fortified fat spread provided 1.6 g/day
      of plant sterols derived from edible vegetable oils and fatty acids from
      sunflower seed oil. The plant sterol content consisted of sitosterol esters
      (50%), campesterol esters (25%), stigmasterol esters (20%) and 10% of other
      esters. Data in 53 hypercholesterolemic patients (31 females and 22 males) who
      completed the study were as follows: patients were 58+/-12 years of age with mean
      body mass index 23.5+/-2.8 kg/m2 (mean+/-SD). No adverse side-effects of the diet
      were reported. Plasma total cholesterol and LDL-C concentrations were
      significantly reduced by 6.4% and 8.8%, respectively, after using the spread
      enriched in plant sterols, as compared to controls (0.0% and 1.3%, respectively).
      No effect on high density lipoprotein-cholesterol (HDL-C) and lipoprotein(a)
      concentrations was detected. When subjects were divided in two subgroups
      according to fibrate treatment, supplementation with phytosterols decreased
      plasma cholesterol and LDL-C by 8.5% and 11.1%, respectively in the subgroup of
      patients treated with fibrates. In the group of patients who did not receive
      fibrates, consumption of plant sterol margarine reduced plasma cholesterol and
      LDL-C by 5.5% and 7.7%, respectively. Spread enriched with plant sterol esters
      significantly lowers blood total and LDL-C levels without affecting HDL-C
      concentrations, in a hypercholesterolemic population following a strict low
      cholesterol diet (NCEP step1). In addition, a combination of fibrate treatment
      and plant sterol ester-supplemented spread offers a safe and effective measure to
      significantly decrease abnormally high cholesterol levels. We conclude that
      phytosterol-enriched spread is a useful adjunctive therapy for
      hypercholesterolemic patients.

PMID- 11522114
TI  - Arterial tissue of arsenic, selenium and iron in Blackfoot disease patients.
AB  - In order to identify arsenic as one of the major factors that cause Blackfoot
      disease on the southwest coast of Taiwan, an atomic absorption spectrophotometric
      method was used to determine arsenic, selenium and iron concentrations in the
      tissue of plantar digital arteries. Samples from 31 patients with Blackfoot
      disease and 30 controls with road traffic accident or occupational injuries were
      studied. The results indicate that the arterial tissue from Blackfoot disease
      patients had higher arsenic concentration (3.06+/-1.42 microg/g) than that from
      healthy controls (0.59+/-0.28 microg/g). The variability was very large 418% at
      p<0.001. It was also noted that the concentrations of selenium (1.23+/-0.41
      microg/g and 1.05+/-0.13 microg/g in patients and controls respectively; with
      variability 17.1%) and iron (72.7+/-34.9 microg/g and 35.2+/-16.5 microg/g in
      patients and controls respectively; with variability 106.5%) were both higher
      than those of controls. However, only the iron concentration was significantly
      different (p<0.05).

PMID- 11522115
TI  - Evaluation of Aution Max AX-4280 automated urine test-strip analyser.
AB  - Aution Max AX-4280, an automated urine test-strip analyser, was evaluated in
      three centres. Method comparison, imprecision, carry-over, linearity, detection
      limit and drift studies were performed for glucose, protein, blood and leukocytes
      using Uriflet S 9UB strips. These strips enable measurement of pH, glucose,
      protein, blood, leukocytes, ketones, bilirubin, urobilinogen and nitrite.
      Specific gravity is determined by the refractive index method. Within-run and
      between-day imprecision, assessed using pooled urines and quality control
      materials, were good. No drift over 24 h or sample carry-over was observed.
      Method comparison with quantitative methods for glucose, protein and specific
      gravity yielded good correlations. Ascorbate negatively interfered with
      haemoglobin, glucose and nitrite measurements. Acetylsalicylic acid lowered pH,
      the effect being greatest when protein was absent. During the assessment period
      no malfunction or breakdown was reported. The Aution Max is easy to use and needs
      minimal maintenance.

PMID- 11522116
TI  - Evaluation of automated enzyme immunoassays for the detection of antibodies to
      extractable nuclear antigens.

PMID- 11522117
TI  - Metrological requirements for clinical laboratories.

PMID- 11522118
TI  - Manufacturer's drug interaction and postmarketing adverse event data: what are
      appropriate uses?
AB  - Governmental agencies overseeing pharmaceutical products use a risk/benefit
      approach to analyse data and make regulatory decisions. Comprehensive public
      dissemination of the safety profile of pharmaceutical products is part of an
      overall strategy for reducing risk associated with the use of any medical
      product. In the US, reports of postmarketing surveillance of approved drugs are
      in the public domain. Some, but not all, of the information in drug interaction
      studies is available to the public through the Freedom of Information Act (FOIA).
      However, there are concerns over the misuse of these data for commercial or other
      gain. The need to protect intellectual property and foster innovation in drug
      development, and concerns of legal liability are often cited as reasons to limit
      full public access to data from drug development studies. In contrast,
      intellectual freedom. public safety, and a mandate for transparent decision
      making processes by regulatory agencies are issues that support open access to
      these data. Ultimately. concern for the public safety justifies open access to
      postmarketing surveillance data, and to a lesser degree, data regarding drug
      interactions in marketed products, and should outweigh the potential loss of
      competitive advantage by pharmaceutical companies.

PMID- 11522119
TI  - Adverse gastrointestinal effects of mycophenolate mofetil: aetiology, incidence
      and management.
AB  - Mycophenolate mofetil (MMF) is a relatively new immunosuppressive drug. It
      inhibits inosine monophosphate dehydrogenase, a key enzyme in the de novo pathway
      of purine synthesis, and thus causes lymphocyte-selective immunosuppression.
      Large clinical trials have revealed the efficacy of MMF in the prevention of
      allograft rejection when administered together with cyclosporin or tacrolimus and
      corticosteroids. Although the adverse effect profile of MMF is comparatively
      benign, gastrointestinal adverse effects are a major concern. These effects are
      partially explained by the increased immune suppression, by the mode of action
      and by interactions, particularly with other immunosuppressants. The aetiology of
      the rarest gastrointestinal adverse effects is still not completely clear.
      Therapy depends upon the clinical gravity of the adverse effects and is therefore
      a case of waiting and ob- serving. An adjustment of dosage of immunosuppressants
      according to the clinical situation and, particularly in the case of MMF,
      spreading the total dosage over more than 2 daily doses are often sufficient.
      Should adverse effects persist for a longer period of time and be of a more
      serious nature, a comprehensive invasive diagnostic process is necessary,
      including endoscopy and biopsy and the search for opportunistic infections. In
      this case, dosage reduction or the complete withdrawal of MMF seems to be
      unavoidable. Severe gastrointestinal complications with MMF are rare, but when
      they do occur they may require extensive diagnosis and treatment. In the future,
      therapeutic drug monitoring and, where necessary, pharmacological modifications
      of MMF could lead to a further reduction of adverse effects with an equal or even
      increased efficacy.

PMID- 11522122
TI  - Safety profile of tolterodine as used in general practice in England: results of
      prescription-event monitoring.
AB  - BACKGROUND: Unstable bladder symptoms are a common problem in general practice.
      Drug therapy with anticholinergic drugs is frequently used in the management of
      this condition. However such drugs are associated with a high incidence of
      anticholinergic adverse effects. Tolterodine is a competitive anticholinergic
      agent, selective for the bladder as opposed to the salivary glands. OBJECTIVE: To
      monitor the safety of tolterodine as used in general practice patients in England
      for the treatment of urinary frequency, urgency and incontinence. DESIGN:
      Prospective observational cohort study. PATIENTS AND PARTICIPANTS: 14,526
      patients [mean age 62.7 (SD 16.4) years; 68.6% female]. METHODS: Patients
      prescribed tolterodine in general practice, soon after the release of the drug in
      the UK, were followed up for a minimum of 6 months using the technique of
      prescription-event monitoring (PEM). RESULTS: The most common adverse events
      reported were dry mouth, headache, malaise, constipation, dyspepsia, nausea and
      vomiting and pain in abdomen. We identified some uncommon events as possible
      adverse drug reactions--notably hallucinations, tachycardia and palpitations. The
      prevalence of these events was compared with that in patient cohorts for other
      drugs on the PEM database. The age- and sex-adjusted relative risk of
      hallucinations on tolterodine compared with 10 drugs of other therapeutic
      classes, and with terodiline, another drug indicated for bladder instability, was
      4.85 [95% confidence interval (CI) 2.72 to 8.66] and 1.25 (95% CI 0.62 to 2.53),
      respectively. There was no significant difference for tachycardia/palpitation in
      this comparison. CONCLUSIONS: Tolterodine is well tolerated in general practice
      at the recommended daily dose. Hallucinations, tachycardia and palpitations are
      infrequently associated with the drug.

PMID- 11522120
TI  - Risks and benefits of soy phytoestrogens in cardiovascular diseases, cancer,
      climacteric symptoms and osteoporosis.
AB  - Phytoestrogens, plant chemicals classified as isoflavones, coumestans and
      lignans, display estrogen-like activity because of their structural similarity to
      human estrogens and exhibit high affinity binding for the estrogen receptor beta.
      They are common components of food items such as grains, beans, fruits and nuts.
      Isoflavones are primarily found in soybeans and foods made from soy. In
      particular, significant therapeutic properties have been generally attributed to
      soy isoflavones, but most of the claims have been poorly, or not at all,
      confirmed by well designed clinical trials. Such is the case of the purported
      role of soy isoflavones in reducing plasma cholesterol levels. This link is now
      not supported by many authors or by appropriately designed clinical studies. The
      role of isoflavones in cancer prevention, particularly of tumours under endocrine
      control (breast, prostate and others) is again only supported by weak to
      nonexisting clinical evidence. A similarcase is that of the prevention/treatment
      of postmenopausal symptoms and osteoporosis. Disturbing data have been reported
      on potential negative effects of soy isoflavones on cognitive function in the
      aged, particularly relating to tofu intake. Recent studies have finally indicated
      a potential role for soy isoflavones in inducing chromosomal changes in cells
      exposed in vitro and potentiating chemical carcinogens. These findings may not,
      however, be extrapolated to clinical conditions. Available data do not appear to
      unequivocally support beneficial effects of soy isoflavones, and warn against
      their wide use, in the absence of satisfactory clinical findings.

PMID- 11522123
TI  - The effect of drugs and toxins on the process of apoptosis.
AB  - In this review we examine the modifying effect of specific drugs on apoptosis.
      Apoptosis is a type of cell death prevalent during many physiological and
      pathological conditions, consisting of several steps, namely, initiating stimuli,
      transduction pathways, effector mechanisms, nuclear fragmentation, and
      phagocytosis. Pharmacological substances such as glucocorticoids can either
      induce or inhibit the process of apoptosis in various cells depending on the type
      of drug and its concentration. Understanding the mechanisms of interaction of
      drugs with cells undergoing apoptosis could encourage novel therapeutic
      approaches to human diseases in which apoptosis has a critical role.

PMID- 11522121
TI  - Antiretroviral therapy in pregnancy: a focus on safety.
AB  - Antiretroviral compounds differ from most other new pharmaceutical agents in that
      they have become widely prescribed in pregnancy in the absence of proof of
      safety. They are prescribed for the treatment of the mother and to reduce the
      risk of transmission of HIV to the fetus. In the animal models tested to date, no
      increased risk of malformations has been demonstrated for some compounds whereas
      others have been associated with malformations or developmental abnormalities in
      rats, mice or rabbits and, in the case of efavirenz, monkeys. Zidovudine
      monotherapy is still prescribed to reduce the risk of mother-to-child
      transmission of HIV. Combinations of 3 or more compounds are recommended when
      treatment of the mother is deemed necessary because of advanced HIV infection.
      Until recently, in vitro toxicity studies relevant to pregnancy were restricted
      to single agents; no animal teratogenicity or carcinogenesis studies of
      combination therapy have been published. Despite many thousands of women having
      taken antiretroviral therapy to reduce the risk of transmission, documented
      experience in human pregnancy remains sadly lacking, with the possible exception
      of zidovudine which has been prescribed in clinical trials to several hundred
      mother-infant pairs. For other compounds and for the numerous permutations of
      combination therapy, data are available only from small phase I/II studies, from
      retrospective investigations and from the prospective arm of the Antiretroviral
      Pregnancy Register (i.e. pregnancies in women taking antiretrovirals who were
      registered before delivery and then followed up). Antiretroviral monotherapy and
      combination therapy is widely prescribed in pregnancy because: (i) with
      appropriate management, which includes antiretroviral therapy, the risk of mother
      to-child transmission can be reduced from 15 to 25% to less than 1%; (ii)
      pregnant women with advanced HIV infection require therapy; (iii) combination
      therapy with at least 3 compounds significantly reduces morbidity and mortality
      compared with dual or monotherapy; and (iv) the benefits of therapy for both the
      mother and the infant outweigh the risk. The choice of antiretroviral therapy in
      pregnancy may be influenced by the indication (prevention of transmission or
      maternal treatment), past antiretroviral therapy exposure/drug resistance,
      effects of pregnancy on the pharmacokinetics of the drug and factors influencing
      tolerability and adherence. In pregnancy, tolerability may be even more important
      than usual, especially if therapy exacerbates common complications of pregnancy,
      such as vomiting and glucose intolerance.

PMID- 11522124
TI  - Roles of cytochrome p450 in development.
AB  - Cytochrome P450 (CYP) forms are ubiquitous in nature, appearing in almost all
      phyla, with many forms appearing in any organism. About 50 different forms have
      been identified in man, and some of these are found in the embryo, some showing
      temporal dependence. Many of the forms of cytochrome P450 present in one species
      have homologues in other species. For example, CYP1A2 is present in many species,
      including man, rabbits, rodents, fish and fowl. The amino acid sequence identity
      of these homologues is often in excess of 70%. CYP26, too, has more than 61%
      identity in amino acid sequence between fish, fowl and mammals. In view of the
      high degree of conservation of sequence as well as of enzymatic activities, it is
      only reasonable to assume that such strong conservation of sequence also reflects
      a conservation of function. Since the 'xenobiotic metabolizing' enzymes predate
      the production of the many xenobiotics they are known to metabolize, perhaps it
      is reasonable to consider endobiotics as natural substrates for their metabolism.
      Of the identified forms of cytochrome P450 that are present in embryonic tissue,
      we consider the possibility that they serve the organism in support of
      morphogenesis of the embryonic tissue. These forms may either function to
      generate morphogenic molecules or to keep regions free of them, thereby creating
      temporal and spatial regions of morphogen action and supporting region-specific
      changes in cells. One known morphogen, retinoic acid, has the enzymes retinal
      dehydrogenase (RALDH) and CYP26 maintaining its actions, the former responsible
      for its generation and the latter for its elimination. Another form of cytochrome
      P450, CYP1B1 appears also to be involved in differentiation of tissue, with its
      absence resulting in primary congenital glaucoma. However, the nature of the
      morphogen it may maintain still remains to be elucidated.

PMID- 11522125
TI  - Effect of Maharishi Amrit Kalash on age dependent variations in mitochondrial
      antioxidant enzymes, lipid peroxidation and mitochondrial population in different
      regions of the central nervous system of guinea-pigs.
AB  - Age related changes in the mitochondria of different regions of the CNS of two
      age groups of guinea-pigs (10 months and 32 months) were studied. The activities
      of glutathione peroxidase (GPx) and glutathione reductase (GRd) decreased
      significantly (p <0.05) with age in the mitochondrial fractions of cerebral
      cortex, hypothalamus, cerebellum and spinal cord. A significant (p <0.05) age
      related decrease in mitochondrial numerical density was observed in all regions
      studied. Electron microscopic observations revealed various degenerative changes
      in the mitochondria with age. Treatment of the animals with the Ayurvedic herbal
      mixture "Maharishi Amrit Kalash" (MAK), 500 mg/kg body wt. daily for 2 months,
      significantly induced the activity of antioxidant enzymes, and also reversed the
      pathological changes to a considerable extent. MAK increased the activity of GPx
      significantly only in the 32 month-old animals. This shows the specificity of the
      action of MAK.

PMID- 11522126
TI  - Determination of beta-lactamase activities and antibiotic susceptibility of some
      Bacillus strains causing food poisoning.
AB  - Some Bacillus species are important food pathogens. For example, B. cereus is an
      opportunistic pathogen found in raw milk that is a common cause of food
      poisoning. It is of interest to investigate the virulant profiles of Bacillus
      strains isolated from foods and samples associated with food-poisoning outbreaks.
      Nineteen Bacillus strains were isolated from various milk samples. Beta-lactamase
      enzyme activities of these Bacillus strains were evaluated with iodometric and
      chromogenic cephalosporin (nitrocefin) test methods. Five of 19 Bacillus strains
      isolated were positive for beta-lactamase activity. Clavulanate-amoxycillin and
      cephazolin were chosen to test the antibiotic susceptibilities of the beta
      lactamase positive and negative Bacillus strains. Of the five beta-lactamase
      positive Bacillus strains, three were susceptible, and two strains intermediate
      to clavulanate-amoxycillin; one was susceptible, and four strains were
      intermediate to cephazolin. None of the beta-lactamase positive Bacillus strains
      was resistant to both antibiotics. Of the 14 beta-lactamase negative strains,
      five were susceptible to clavulanate-amoxycillin, four strains were intermediate,
      and five strains were resistant; three were susceptible, one intermediate, and
      ten beta-lactamase negative strains were resistant to cephazolin.

PMID- 11522127
TI  - Colony growth rates of microfungal isolates from the north and south facing
      slopes of Evolution Canyon, Mount Carmel, Israel, after irradiation at 10(6) rads
      60Co.
AB  - Species of microfungi were isolated from both the north facing slope (NFS) and
      the south facing slope (SFS) of Evolution Canyon, Mount Carmel, Israel. They were
      examined for growth rates before and after exposure to 10(6) rads of cobalt 60
      irradiation. Above 10(6) rads all growth ceased after 1 day following exposure.

PMID- 11522128
TI  - Monitoring of chemical fertilizers on toxicity of two carbamate insecticides to
      the cyanobacterium Anabaena PCC 7120.
AB  - The effects of individual chemical fertilizers (urea, superphosphate and potash)
      on the toxicity of two carbamate insecticides (carbaryl and carbofuran) to the
      nitrogen-fixing cyanobacterium Anabaena PCC 7120, were studied in vitro at
      partial lethal levels of each insecticide. Urea at 10 and 50 ppm levels reduced
      the toxicity due to carbaryl at 50 ppm partial lethal dose and due to carbofuran
      at 100 and 250 ppm partial lethal doses. Urea at 100 ppm enchanced the toxicity
      of both insecticides. Superphosphate at 10 ppm reduced the toxicity of carbaryl
      at 50 ppm and carbofuran at 100 and 250 ppm, but it enhanced the toxicity due to
      both insecticides at 50 ppm superphosphate. The toxicity due to carbaryl at 40
      and 60 ppm were reduced by 100 and 200 ppm potash, but higher potash levels
      caused enhancement of toxicity. Carbofuran toxicity at 100 ppm was reduced but at
      250 ppm the toxicity was enhanced with 100 ppm potash. Urea, superphosphate and
      potash caused no significant change in number of vegetative cells between the
      successive heterocysts at 10 and 50 ppm of urea and superphosphate, respectively,
      and 100 ppm of potash.

PMID- 11522129
TI  - Quantitative analysis of the elemental composition and the mass of bacterial
      polyphosphate bodies using STEM EDX.
AB  - The quantitative analysis of laboratory grown organisms (Plectonema boryanum and
      Staphylococcus aureus) revealed that a typical in vivo polyphosphate body (PPB)
      contains O (4.3 x 10(-8) microg), C (1.2 x 10(-8) microg), P (6.7 x 10(-9)
      microg), Mg (1.3 x 10(-9) microg), Ca (6.7 x 10(-10) microg), K (6.7 x 10(-10)
      microg), Fe (6.0 x 10(-10) microg), S (5.4 x 10(-10) microg) and Al (5.9 x 10(
      10) microg). Quantitative X-ray analysis of samples from nature showed PPB
      contain O (1.63 x 10(-8) microg), C (4.75 x 10(-9) microg), P (2.50 x 10(-9)
      microg), Mg (5.0 x 10(-10) microg), Ca (2.50 x 10(-10) microg), K (2.50 x 10(-10)
      microg), Fe (2.25 x 10(-10) microg) and S (2.0 x 10(-10) microg). The mass of an
      average polyphosphate body was 6.7 x 10(-8) microg for P. boryanum, 2.5 x 10(-8)
      microg for S. aureus and for microbes from the natural environment 6.3 x 10(-8)
      microg. The results indicate that the PPB may have other unknown functions in
      addition to essential element storage, acting as a detoxification method by
      sequestering heavy metals and providing a homeostasis system in the cell.

PMID- 11522130
TI  - Primary stages in photosignal transduction leading to step-up photophobic
      response in the unicellular eukaryote Blepharisma japonicum.
AB  - In order to elucidate the primary stage in the blepharismin phototransduction
      pathway, changes in the molecular structure of light-exposed blepharismins and
      oxyblepharismins, were examined. When exposed to light, blepharismins (pink form)
      were converted into oxyblepharismins (blue form) or dissociated into stentorins/p
      hydroxybenzaldehyde with an O2-requiring process, whereas light-exposed
      oxyblepharismins were not dissociated into stentorins/p-hydroxybenzaldehyde.
      Since both blepharismins and oxyblepharismins can activate the phototransduction
      chain leading to the step-up photophobic response presumably through the same
      pathway, dissociation of p-hydroxybenzaldehyde may not be involved in signal
      transduction. The fact that the step-up photophobic response requires O2, and
      both blepharismins and oxyblepharismins produce hydroxyl (OH) radicals probably
      derived from O2 implies that OH radicals may activate the photosignalling
      pathway. The step-up photophobic response was not suppressed by a spin trapping
      reagent for hydroxyl radicals. Other possible primary responses leading to the
      step-up photophobic response are discussed.

PMID- 11522131
TI  - Relationship between T lymphocyte responsiveness and T-helper1/T-helper2 type
      cytokine release in chronic hepatitis C: a critical reappraisal.
AB  - Recruitment of virus-specific T lymphocyte subpopulations to liver sites in
      chronic hepatitis C virus (HCV) infection implies a key role for the immune
      response in host-virus interaction. In spite of a multispecific and polyclonal
      cytotoxic function exerted by CD8+ lymphocytes, CD4-mediated activity is weak.
      This allows the infection to persist which in turn is responsible for the
      development of chronic hepatitis C (CH-C). Such a finding outlines the occurrence
      of a possible relationship between cytokine (CK) production by CD4 subsets, i.e.
      T helper (Th)1 or Th2 cells, and the clinical outcome. A prevalence of Th1
      derived CK occurs in infected liver, while increased amounts of Th2-related CK
      are usually found in peripheral blood. Moreover, peripheral blood mononuclear
      cell (PBMC) cultures from CH-C subjects exhibit an impaired interferon (IFN)
      gamma production and an increase of interleukin (IL)-12 p70 release after
      stimulation. The latter pattern seems to be due to the enhanced release of IL-12
      p40 homodimers, which antagonize IL-12 p70 bioactivity and favour IL-10-induced
      effects. These results suggest that further extensive studies on the imbalance of
      the CK network at a molecular level are required to improve the therapeutical
      approach in CH-C subjects.

PMID- 11522132
TI  - Do national medicinal drug policies and essential drug programs improve drug
      use?: a review of experiences in developing countries.
AB  - Increasing concerns regarding access to and appropriateness of medicinal drug use
      have led many governments in developing countries to develop national policies
      and regulations intended to increase the affordability, supply, safety, and
      rational use of pharmaceuticals. However, little is known about the intended and
      unintended impacts of these social experiments on actual drug use. We conducted a
      critical review and synthesis of the international literature in an attempt to
      define the current state of knowledge regarding drug policy effects on drug use,
      and to extract from the evidence important lessons for future policy and
      research. Literature sources included the archives and computerized databases,
      articles published in medical and pharmacy journals, as well as published
      annotated bibliographies. The evaluated interventions included three broad
      categories: (1) multi-component national drug policies including essential drug
      programs; (2) drug supply and cost-sharing programs; and (3) regulatory measures.
      Most of these studies utilized weak research designs that evaluated programs
      solely on the basis of post-intervention measures. Only two studies measured pre
      policy utilization, but did not include a control group. Thus, none of the
      results are conclusive, and the findings represent, at best, hypotheses for more
      rigorous studies of policy impacts. Some suggestive findings include an
      association between increases in the supply of essential drugs (combined with
      training) and more appropriate use of medications in primary care settings. In
      addition, preliminary data suggest some unintended effects of de-registration of
      drugs or upward reclassification of specific medicines. Similarly, loosening
      restrictions have sometimes been accompanied by increased dispensing of specific
      drugs by unqualified personnel. The available studies focused only on a few
      categories of national and regulatory policies. Because of poor study design, the
      results do not provide valid data to determine whether national drug policies
      improve drug use. Moreover, no studies have evaluated the effects of major and
      recent changes, such as increased use of product patents, national pharmaceutical
      insurance policies, and increased privatization of pharmaceutical products and
      services. Future studies need to explore the consequences of these emerging
      developments on drug access and use. Despite the difficulties inherent in
      evaluation of national policies, stronger research designs can and should be
      carried out. Interrupted time-series analysis and other more rigorous designs
      should become standard designs for policy evaluation in the same way that
      standard treatment guidelines are intended to guide medical practice.

PMID- 11522133
TI  - Navigating the time-space context of HIV and AIDS: daily routines and access to
      care.
AB  - Geographers have shown that daily activities and social networks are constrained
      by time-space, but there are also enabling facets or opportunities created by
      daily routines for accessing material and emotional resources, improving quality
      of life, and even challenging existing power relations. Time-geography in this
      paper is taken as a starting point to assess how individuals living with HIV and
      AIDS navigate the complex and often difficult time space contexts defining their
      access to services. The concept of time space windows of access is offered as a
      way to understand the opportunities created by daily routines and social network
      interaction even in highly marginalized social, economic, and political
      circumstances. Survey data and in-depth interviews conducted with a diverse group
      of persons living with HIV and AIDS are used to illustrate this conceptual
      argument. Results indicate that the time space characteristics of daily routines,
      such as frequency of activities, variety or heterogeneity in activities, and
      whether activities are self- or social network-oriented, serve to define the
      availability of temporal and spatial windows of access to services. In addition,
      daily routines seem to matter for specific types of services, and have a limited
      role to play in terms of primary medical services or those associated with basic
      needs. The implications of these findings for theorizing and for enhancing access
      to services are provided.

PMID- 11522134
TI  - Gender and health services use for a mental health problem.
AB  - This study addresses whether the predictors of seeking help for a mental health
      problem differ by gender. An adaptation of Andersen's Socio-Behavioral Model is
      used to identify factors associated with seeking care for a mental health
      problem. Data are derived from two waves of a community survey undertaken in 1992
      1993 and in 1993-1994 among a probability sample of adults (18-69 years),
      residing in poor areas of Puerto Rico. Paired data was used from those
      individuals who responded to both waves of the survey for a total of 3221
      community respondents. Responses from wave 1 were used to predict mental health
      service use in wave 2. The dependent variable is any use of outpatient mental
      health services in the year preceding the second interview. Logistic regression
      was used to model the effects of the independent variables on use. Males and
      females were found to use mental health services in nearly equal proportions.
      Gender did not have a main effect on use when other covariates were controlled.
      Significant interactions with gender were found for several predictors of use.
      The largest intervention effects were encountered in our need for care
      indicators. Having a definite need for mental health care and poor self-rated
      mental health had a larger effect on predicting use of services for men than they
      do for women. It is concluded that strategies designed to improve access to
      mental health services for minority disadvantaged populations ought to take into
      account gender differences in the predictors of use. Studies addressing factors
      influencing health services utilization for a mental health problem should
      consider stratifying their sample by gender. Future research should establish
      whether or not these findings are sustained with other population groups.

PMID- 11522135
TI  - Adoption of smart cards in the medical sector: the Canadian experience.
AB  - This research evaluates the factors influencing the adoption of smart cards in
      the medical sector (a smart card has a micro-processor containing information
      about the patient: identification, emergency data (allergies, blood type, etc.),
      vaccination, drugs used, and the general medical record). This research was
      conducted after a pilot study designed to evaluate the use of such smart cards.
      Two hundred and ninety-nine professionals, along with 7248 clients, used the
      smart card for a year. The targeted population included mostly elderly people,
      infants, and pregnant women (the most intensive users of health care services).
      Following this pilot study, two surveys were conducted, together with numerous
      interviews, to assess the factors influencing adoption of the technology. A
      general picture emerged. indicating that although the new card is well-perceived
      by individuals, tangible benefits must be available to motivate professionals and
      clients to adopt the technology. Results show that the fundamental dimension that
      needs to be assessed before massive diffusion is the relative advantage to the
      professional. The system must provide a direct benefit to its user. The relative
      advantage of the system for the professional is directly linked to the obligation
      for the client to use the card. The system is beneficial for the professional
      only if the information on the card is complete. Technical adequacy is a
      necessary but not sufficient condition for adoption.

PMID- 11522136
TI  - Innovation and regulation in human implant technologies: developing comparative
      approaches.
AB  - Human implant technologies are subject to continual innovation and proliferation,
      raising important issues for technology testing, healthcare sciences, clinical
      performance and risk assessment, and regulation. The regulatory environment of
      medical devices is being shaped by harmonisation of standards in the European
      Union. The aim of this paper is to compare the histories and current regulatory
      environment of two technologies, breast implants and artificial hips, and to
      consider the implications of this comparison for a sociological healthcare
      research agenda to investigate the issues raised. The main focus is upon
      developments in the United Kingdom. Major points of contrast between the two
      technologies include the institutional contexts in which clinical evidence has
      been marshalled for government attention; the relative importance of strategic
      alliances between clinicians and manufacturers in the innovation process; the
      degree of public controversy evident; the varying definitions of an 'adverse
      incident' within medical device vigilance systems; and in the UK the presence of
      a national register for breast implants but not for hip implants. Inter-national
      contrasts in these dimensions are noted. The analysis suggests that improved
      understanding is required of the institutional, organisational and professional
      processes involved in implant technology innovation and regulation. A comparative
      research agenda is proposed, focusing upon: innovativeness and proliferation;
      safety and technological standards; clinical and social outcomes; and
      consumer/user information and choice. It is concluded that research in these
      areas will enhance the 'evidence-base' for the evaluation of human implant
      technologies in the context of their innovatory and regulatory environments.

PMID- 11522137
TI  - Social deprivation, income inequality, social cohesion and dental caries in
      Brazilian school children.
AB  - This ecological study investigated the associations between social deprivation,
      income inequality and social cohesion and dental caries levels in school children
      of the Distrito Federal, Brazil. Three sources of data were used: (1) area-based
      data from a 1997 social survey carried out on 13,000 families, (2) 1995 census
      data collected for the Government of the Distrito Federal (GDF), and (3) dental
      caries data from a 1997 oral health survey on 7296 6-12-year-old school children.
      Results of simple linear regression showed that percent with less than eight
      years of education (P = 0.03) and percent who did not have a maid (P = 0.009),
      were negatively statistically significantly associated with the percent of
      children free of caries. None of the deprivation measures were statistically
      significantly associated with mean DMF-T scores (P > 0.05). GINI coefficient, an
      indicator of social inequalities, was negatively statistically significantly
      associated with both measures of dental caries experience, percent of caries free
      (P = 0.003) and mean DMF-T scores (P = 0.01). Per thousand number of homicides or
      attempted homicides, an indicator of social cohesion was of marginal statistical
      significance associated with caries experience. Results of multiple linear
      regression analyses showed that only the Gini coefficient remained statistically
      significantly associated with both dental clinical measures used, after adjusting
      for potential confounding. In conclusion, relative rather than absolute levels of
      income were stronger determinants of the onset of caries in this study.

PMID- 11522138
TI  - In their own words: a model of healthy aging.
AB  - Many previous studies have assessed the aging process by measuring clinical and
      functional variables. To supplement that quantitative understanding, we asked
      older people what constitutes their health and contributes to it. Using grounded
      theory-type methods, we analyzed semi-structured interviews with 22 study
      subjects, who were randomly selected from among those whose reported perceived
      health differed from that predicted by a regression model constructed from data
      from a randomized trial of a primary care intervention. We focused on disparate
      cases to identify factors that best discriminate between more and less healthy
      aging. Interview questions targeted perceptions of health; well-being; valued
      abilities, activities, and relationships; social support; control; sense of
      coherence; and personal outlook. A model of healthy aging emerged. To these older
      people health meant going and doing something meaningful, which required four
      components: something worthwhile to do, balance between abilities and challenges,
      appropriate external resources, and personal attitudinal characteristics (e.g.,
      positive attitude vs. "poor me"). By reframing healthy aging in older people's
      own terms, this model encourages interdisciplinary support of their desired goals
      and outcomes rather than only medical approaches to deficits and challenges.

PMID- 11522139
TI  - The reprofessionalisation of community pharmacy? An exploration of attitudes to
      extended roles for community pharmacists amongst pharmacists and General
      Practioners in the United Kingdom.
AB  - In the light of recent developments within the British National Health Service
      some sociologists have suggested that the medical profession's status is under
      threat. They have specified a range of factors contributing to this state of
      affairs, such as the new consumerism; however, it is thought that attempts by
      other, related occupations at reprofessionalisation are particularly significant
      in this trend. It may be possible to understand recent initiatives at extending
      community pharmacists' role within this framework. This paper suggests that while
      community pharmacy is developing strategies to enhance its professional status,
      it is not so much an attempt at usurping general practitioners'(GPs) (primary
      care doctors') role as a bid for survival, especially on the part of the rank and
      file. However, GPs do not necessarily see the initiatives in this light. Although
      many GPs are accommodating some changes in community pharmacy, they also perceive
      some of the initiatives as a threat to their autonomy and control, this was
      especially evident in representative bodies such as the Local Medical Committee.
      Doctors' accommodating attitudes were qualified with traditional attitudes of
      dominance such as 'limitation' and 'exclusion'. Such attitudes could prevent
      community pharmacy from achieving professional status. However, there is also
      evidence that pharmacists themselves contribute to this situation because many of
      them also attribute ultimate authority to doctors. Moreover, they are held back
      by internal occupational divisions particularly between retail pharmacists and
      employee pharmacists, with the former being the most insecure.

PMID- 11522140
TI  - The effects of sex and age of responders on the reliability of self-diagnosed
      infection: a study of self-reported urinary schistosomiasis in Tanzanian school
      children.
AB  - Self-reported schistosomiasis has been proven to be a reliable estimation of the
      prevalence of infection in school children. For the first time, this paper
      presents an investigation into the use of self-reported schistosomiasis to
      estimate the prevalence of urinary schistosomiasis, due to Schistosoma
      haematobium, in school children with particular emphasis on whether the age and
      sex of respondents influences the reliability of diagnosis. It is shown first,
      that the prevalence and intensity of infection vary with sex; infection in boys
      is always more prevalent and more intense than in girls of the same age and
      second, that age and sex influence the reliability of self-reported
      schistosomiasis as a diagnostic method. Age and sex are factors that should be
      considered when implementing control measures in endemic areas.

PMID- 11522141
TI  - Estimating the employment and earnings costs of mental illness--recent
      developments in the United States, Marcotte and Wilcox-Gok.

PMID- 11522142
TI  - Kinematic comparisons of 1996 Olympic baseball pitchers.
AB  - The aim of this study was to compare and evaluate the kinematics of baseball
      pitchers who participated in the 1996 XXVI Centennial Olympic Games. Two
      synchronized video cameras operating at 120 Hz were used to video 48 pitchers
      from Australia, Japan, the Netherlands, Cuba, Italy, Korea, Nicaragua and the
      USA. All pitchers were analysed while throwing the fastball pitch. Twenty-one
      kinematic parameters were measured at lead foot contact, during the arm cocking
      and arm acceleration phases, and at the instant of ball release. These parameters
      included stride length, foot angle and foot placement; shoulder abduction,
      shoulder horizontal adduction and shoulder external rotation; knee and elbow
      flexion; upper torso, shoulder internal rotation and elbow extension angular
      velocities; forward and lateral trunk tilt; and ball speed. A one-way analysis of
      variance (P < 0.01) was used to assess kinematic differences. Shoulder horizontal
      adduction and shoulder external rotation at lead foot contact and ball speed at
      the instant of ball release were significantly different among countries. The
      greater shoulder horizontal abduction observed in Cuban pitchers at lead foot
      contact is thought to be an important factor in the generation of force
      throughout the arm cocking and arm acceleration phases, and may in part explain
      why Cuban pitchers generated the greatest ball release speed. We conclude that
      pitching kinematics are similar among baseball pitchers from different countries.

PMID- 11522143
TI  - Season-of-birth bias in association football.
AB  - In this longitudinal study, we assessed the frequency of birth dates for boys
      selected for the Football Association National School. Birthdays were divided
      into three periods of the year: January to April, May to August and September to
      December. We compared data over a 5 year period and concluded that there is
      indeed a bias towards selecting older children. Furthermore, analysis of separate
      data revealed a shift of bias when comparing two different start dates, namely
      September and January. Our findings show that the youngest children from the
      January start date (born September to December) are selected significantly more
      often than the youngest children from the September start date (born May to
      August). Interestingly, even when the influence of body mass was reduced, the
      selection bias towards the older players remained.

PMID- 11522144
TI  - Creatine kinase, myosin heavy chains and magnetic resonance imaging after
      eccentric exercise.
AB  - The aim of this study was to examine the relationship between myosin heavy chain
      (MHC) release as a specific marker of slow-twitch muscle fibre breakdown and
      magnetic resonance imaging (MRI) of skeletal muscle injury after eccentric
      exercise. The effects of a single series of 70 high-intensity eccentric
      contractions of the quadriceps femoris muscle group (single leg) on plasma
      concentrations of creatine kinase and MHC fragments were assessed in 10 young
      male sport education trainees before and 1 and 4 days after exercise. To
      visualize muscle injury, MRI of the loaded thigh was performed before and 4 days
      after the eccentric exercise. All participants recorded an increase (P < 0.05) in
      creatine kinase after exercise. In five participants, T2 signal intensity was
      unchanged post-exercise compared with pre-exercise and MHC plasma concentration
      was normal; however, they showed an increase (P < 0.05) in creatine kinase after
      exercise. For the remaining five participants, there was an increase in T2 signal
      intensity of the loaded vastus intermedius and vastus lateralis. These changes in
      MRI were accompanied by an increase in MHC plasma concentration (P< 0.01) as well
      as an increase in creatine kinase (P < 0.01). We suggest that changes in MRI T,
      signal intensity after muscle damage induced by eccentric exercise are closely
      related to damage to structurally bound contractile filaments of some muscle
      fibres. Additionally, MHC plasma release indicates that this damage affects not
      only fast-twitch fibres but also some slow-twitch fibres.

PMID- 11522145
TI  - Effects of active, passive or no warm-up on metabolism and performance during
      high-intensity exercise.
AB  - The aim of this study was to determine the influence of type of warm-up on
      metabolism and performance during high-intensity exercise. Eight males performed
      30 s of intense exercise at 120% of their maximal power output followed, 1 min
      later, by a performance cycle to exhaustion, again at 120% of maximal power
      output. Exercise was preceded by active, passive or no warm-up (control). Muscle
      temperature, immediately before exercise, was significantly elevated after active
      and passive warm-ups compared to the control condition (36.9 +/- 0.18 degrees C,
      36.8 +/- 0.18 degrees C and 33.6 +/- 0.25 degrees C respectively; mean +/- sx)
      (P< 0.05). Total oxygen consumption during the 30 s exercise bout was
      significantly greater in the active and passive warm-up trials than in the
      control trial (1017 +/- 22, 943 +/- 53 and 838 +/- 45 ml O2 respectively). Active
      warm-up resulted in a blunted blood lactate response during high-intensity
      exercise compared to the passive and control trials (change = 5.53 +/- 0.52, 8.09
      +/- 0.57 and 7.90 +/- 0.38 mmol x l(-1) respectively) (P < 0.05). There was no
      difference in exercise time to exhaustion between the active, passive and control
      trials (43.9 +/- 4.1, 48.3 +/- 2.7 and 46.9 +/- 6.2 s respectively) (P= 0.69).
      These results indicate that, although the mechanism by which muscle temperature
      is elevated influences certain metabolic responses during subsequent high
      intensity exercise, cycling performance is not significantly affected.

PMID- 11522146
TI  - Energy conversion strategies during 100 m sprinting.
AB  - The aims of this study were to examine energy conversion strategies during 100 m
      sprinting and to determine whether there are opportunities for performance
      enhancement beyond the usual 'maximum effort throughout' strategy. The roles of
      aerodynamic drag and kinetic energy recovery on the overall whole-body energy
      balance are discussed. A mathematical model based on sprinting with maximum
      effort, converting chemical energy as rapidly as possible to mechanical energy,
      is used to calculate a reference performance. Subsequent calculations show the
      effect of inserting a period of constant-speed running on overall running time.
      The paper explores how the timing of entry into the second phase affects the
      overall running time. Overall, the calculations show that no benefits result from
      adopting a running strategy involving the insertion of a constant-speed phase;
      the analysis confirms that the strategy of running with maximum effort is the
      optimum. For a certain range of conditions, the insertion of a short period of
      constant-speed running has been shown to have a negligible effect on overall
      running time. For elite male athletes, the constant-speed phase may be entered
      between 55 and 60 m from the start line, while for elite female athletes the
      corresponding values are between 46 and 53 m from the start.

PMID- 11522147
TI  - The influence of self-efficacy and past behaviour on the physical activity
      intentions of young people.
AB  - The aim of the present study was to assess the influence of self-efficacy and
      past behaviour on young people's physical activity intentions using an augmented
      version of Ajzen's Theory of Planned Behaviour. We hypothesized that self
      efficacy would exhibit discriminant validity with perceived behavioural control
      and explain unique variance in young people's intentions to participate in
      physical activity. We also expected that past physical activity behaviour would
      attenuate the influence of attitude, subjective norms, perceived behavioural
      control and self-efficacy on intention. The sample comprised 1,152 young people
      aged 13.5 +/- 0.6 years (mean +/- s) who completed inventories assessing their
      physical activity intentions, attitudes, subjective norms, perceived behavioural
      control, self-efficacy and past physical activity behaviour. A confirmatory
      factor analysis demonstrated that the constructs of the Theory of Planned
      Behaviour achieved discriminant validity. Furthermore, the measures of attitudes,
      subjective norms, perceived behavioural control and self-efficacy were
      significantly related to their respective belief-based measures, supporting the
      concurrent validity of the measures of the Theory of Planned Behaviour. A non
      standard structural equation model demonstrated that attitude and self-efficacy
      were strong predictors of physical activity intention, but perceived behavioural
      control and subjective norms were not. Self-efficacy attenuated the influence of
      attitudes and perceived behavioural control on intention. Past behaviour
      predicted intention directly and indirectly through self-efficacy and attitude.
      The present findings demonstrate that young people with positive attitudes and
      high self-efficacy are more likely to form intentions to participate in physical
      activity. Furthermore, controlling for past physical activity behaviour revealed
      that the unique effects of self-efficacy and attitudes on young people's physical
      activity intentions were unaltered.

PMID- 11522148
TI  - Pre-shot EEG alpha-power reactivity during expert air-pistol shooting: a
      comparison of best and worst shots.
AB  - The aim of this study was to examine the proposal that pre-shot occipital
      electroencephalogram (EEG) alpha-power reactivity would not only associate with,
      but also have a causal role in, the relative success of performance outcome in
      expert air-pistol shooting. Six expert air-pistol shooters performed a sixty-shot
      match, individually, while electroencephalograms were captured from occipital and
      anterior-temporal electrode sites during the aiming period (3 x 2 s epochs)
      before shot release. The five best shots and five worst shots were selected for
      each shooter on the basis of four shot quality indicators, and pre-shot EEG alpha
      power for best shots was compared with that of worst shots. Occipital EEG alpha
      power was found to increase during epochs 1-3 before best shots, but to decrease
      before worst shots; it was significantly greater during the final pre-shot epoch
      of best shots. This finding suggests that visual attention to the pistol and
      target was gradually suppressed during the pre-shot period of best shots, whereas
      it gradually increased before worst shots. In addition, significantly greater EEG
      alpha power was found at the left than at the right anterior-temporal site,
      lending support to the robust findings of previous target-sport studies. We
      conclude that the participants were able to shoot at the target with greatest
      success when not having maximal visual attention on where the pistol was aimed
      and that suppression of visual attention during the final seconds of the pre-shot
      period is a necessary prerequisite for automatic shot execution, as controlled by
      mechanisms of intention.

PMID- 11522149
TI  - Nicotine patches in Japan.

PMID- 11522151
TI  - Abstracts of the International Continence Society 31st annual meeting. Seoul,
      Korea, 18-21 September 2001.

PMID- 11522150
TI  - Use of Shewhart's technique.

PMID- 11522152
TI  - International Society for Experimental Hematology 30th annual meeting. Tokyo,
      Japan, August 25-28, 2001. Abstracts.

PMID- 11522153
TI  - Sun exposure and sun-protection behaviors and attitudes among U.S. youth, 11 to
      18 years of age.
AB  - BACKGROUND: Adolescence is a high-risk period for the development of melanoma and
      nonmelanocytic skin cancers later in life. This study examines the prevalence and
      correlates of sun-protection practices among U.S. youth. METHODS: During July
      October, 1998, a national, population-based telephone survey was conducted (N =
      1,192 paired interviews of youth and their parents). Weighted prevalence and
      adjusted prevalence odds ratios and 95% confidence intervals were estimated.
      Multiple logistic regression analyses examined associations between
      sociodemographics, attitudes, and other modifiable correlates to specific
      behaviors. RESULTS: Routinely practiced sun-protection behaviors among youth on
      sunny days were wearing sunglasses (32%) or long pants (21%), staying in the
      shade (22%), and applying sunscreen (31%). Fifty-eight percent used a sunscreen
      with SPF > or =15 when at the beach or pool. Age, sex, and sun sensitivity were
      associated with substantial variation in some sun-protection behaviors. Factors
      associated with specific sun-protection behaviors included a lower appeal to
      tanning, a higher perceived benefit of sun protection, and information from
      family and friends about sun protection. CONCLUSION: Effective sun protection is
      practiced by less than one-third of U.S. youth. This baseline survey will help to
      monitor progress in skin cancer prevention in this critical age group in the
      future.

PMID- 11522154
TI  - Attention deficit hyperactivity disorder: a message from Preventive Medicine and
      your physician.

PMID- 11522155
TI  - Impact of skin cancer prevention on outdoor aquatics staff: the Pool Cool program
      in Hawaii and Massachusetts.
AB  - BACKGROUND: Aquatic staff, including lifeguards, are exposed to intense sunlight
      for many hours each day and are likely to be at a relatively high risk for
      developing skin cancer. However, no interventions have been specifically directed
      to staff at outdoor swimming pool sites. METHODS: We conducted a randomized
      controlled trial among aquatic staff at 28 outdoor pool sites in Hawaii and
      Massachusetts. Intervention pools received sun protection education and control
      pools received education on child injury prevention. Staff in both arms received
      orientation sessions and led instruction during swim lessons. Analysis of
      covariance was used to compare and test for changes in outcome variables (sun
      protection habits and sunburning rates of aquatic staff) and pool protection
      policies. Surveys were completed at the beginning and end of the summer. RESULTS:
      Surveys were completed by 220 aquatics staff at baseline; 194 surveys were
      completed at posttest. Compared with staff at control pools, sun protection
      policies (P < 0.04) and sunburning rates (P < 0.05) improved at sun protection
      pools from baseline to posttest. However, the difference in the mean score of all
      sun protection habits between the two study groups was nonsignificant.
      CONCLUSION: The Pool Cool sun protection intervention had significant effects on
      lifeguards' sunburn rates and pool sun safety policies but did not improve
      reported sun protection behaviors. More intensive strategies may be needed to
      influence aquatics workers who have already begun to adopt skin cancer prevention
      practices.

PMID- 11522156
TI  - Promoting sun safety among zoo visitors.
AB  - BACKGROUND: Each year, millions of children visit zoological parks, where they
      are exposed to long bouts of ultraviolet radiation (UVR). We conducted a study in
      the winter and replicated it in the summer to evaluate an intervention for
      reducing UVR exposure during the zoo visit. METHODS: Each study used a
      nonequivalent control group design: one zoological site received the intervention
      and a second received evaluation only. Key outcome measures consisted of observed
      prevalence of hat use by exiting children (N = 8,721 and 8,524, respectively, in
      winter and summer studies) and purchase rates of sunscreen and hats in zoo gift
      shops. Intervention consisted of tip sheets for parents, children's activities,
      prompts, and discounts off the price of sunscreen and sun-protective hats.
      RESULTS: In the summer study, sales of both sunscreen and target hats increased
      significantly at the intervention site relative to the control site, whereas in
      the winter study, only sunscreen sales at the intervention site had a significant
      (relative) increase. Children's hat use increased significantly at the
      intervention site, but only in the winter study. CONCLUSIONS: The multicomponent
      program was effective in promoting purchases of sun-safe items, but its impact on
      children's hat use was inconclusive.

PMID- 11522157
TI  - Smoking in Colombian medical schools: the hidden curriculum.
AB  - BACKGROUND: Tobacco companies are focusing their interest in less developed
      countries. In the absence of governmental opposition, physicians are expected to
      lead tobacco control efforts. We studied Colombian medical students' smoking
      prevalence and tobacco attitudes. METHODS: First- and fifth-year students from 11
      medical schools in seven Colombian cities answered anonymous, self-administered,
      38-item questionnaires. Additionally, smokers answered the Fagerstrom Test for
      Nicotine Dependence (FTND). RESULTS: Two thousand twenty-one students (males
      50.6%; age 15-44, median 19) completed the survey; average response rate was
      89.9%. Globally 25.9% of students were current smokers (males 27.9%, females
      24.0%). Living at higher altitude and attending private universities were
      associated with higher prevalence (P < 0.001). Males had a higher chance of
      having given up smoking (P < 0.05); 91.3% of current smokers would like to quit;
      67.3% of all smokers and 44.8% of daily smokers scored 0 in the FTND. Prevalence
      was similar among first- and fifth-years, but fifth-year students were more
      complacent with smoking in health centers and showed a lesser desire to quit.
      CONCLUSIONS: Medical students' smoking prevalence is similar to that of the
      general population. Tobacco control strategies need to be included in the
      curriculum. Nicotine addiction does not seem to be the main perpetuating factor.

PMID- 11522158
TI  - HIV/STD-protective benefits of living with mothers in perceived supportive
      families: a study of high-risk African American female teens.
AB  - BACKGROUND: The joint influence of living with the mother in a perceived
      supportive family may be an important HIV/STD-protective factor among sexually
      active female adolescents. METHODS: Sexually active African American female
      adolescents (N = 522) completed a self-administered survey and structured
      interview. Adolescents scoring high on family support and reporting that their
      mother lived with them were compared with the remaining adolescents in respect to
      unprotected vaginal sex (past 30 days), sex with a non-steady partner (past 6
      months), communication with sex partners, attitudes toward condoms, and perceived
      ability to negotiate condom use. Logistic regression analyses controlled for the
      influence of parent-adolescent communication about sex and parental monitoring.
      RESULTS: Adolescents residing with their mothers in a perceived supportive family
      were more likely to communicate with their sex partners about sexual risk (OR =
      1.53). They were less likely to report sex with a non-steady partner (OR = 0.51)
      or having unprotected sex with a steady partner (OR = 0.52) or any partner (OR =
      0.55). CONCLUSIONS: Controlled analyses suggest that living with the mother in a
      perceived supportive family is an important HIV/STD-protective factor among
      female adolescents. HIV/STD prevention programs for female adolescents that
      include the mothers may promote positive and lasting effects.

PMID- 11522159
TI  - Associations of depression, self-esteem, and substance use with sexual risk among
      adolescents.
AB  - BACKGROUND: Adolescents are the population at highest risk for acquiring sexually
      transmitted diseases (STDs). Previous research has suggested that mental health
      problems, including depression and low self-esteem, may play an important role in
      the development and maintenance of sexual risk behaviors. METHODS: National
      Longitudinal Study of Adolescent Health data from baseline interviews of 7th-12th
      graders reporting sexual intercourse in the preceding year were analyzed. Using
      logistic regression, associations of depressive symptoms, self-esteem, and
      substance use with condom nonuse at last sexual intercourse and with ever having
      had an STD were explored separately for each gender. RESULTS: Among boys (N =
      3,192), depressive symptoms were associated with an increased risk of condom
      nonuse at last sexual intercourse. The association between depressive symptoms
      and STD appeared to be mediated by alcohol and marijuana use. For girls (N =
      3,391), depressive symptoms were associated with a history of STD, but not with
      condom nonuse. Self-esteem was not significant in any model that included
      depressive symptoms. CONCLUSIONS: Adolescents with depressive symptoms are at
      risk for not using a condom and for having an STD. Further research is needed to
      elucidate the relationship among depression, substance use, and sexual risk to
      optimize STD prevention strategies for adolescents.

PMID- 11522160
TI  - Community-based cancer screening for underserved women: design and baseline
      findings from the Breast and Cervical Cancer Intervention Study.
AB  - BACKGROUND: Underutilization of breast and cervical cancer screening has been
      observed in many ethnic groups and underserved populations. Effective community
      based interventions are needed to eliminate disparities in screening rates and
      thus to improve prospects for survival. METHODS: The Breast and Cervical Cancer
      Intervention Study was a controlled trial of three interventions in the San
      Francisco Bay Area from 1993 to 1996: (1) community-based lay health worker
      outreach; (2) clinic-based provider training and reminder system; and (3) patient
      navigator for follow-up of abnormal screening results. Study design and a
      description of the interventions are reported along with baseline results of a
      household survey conducted in four languages among 1599 women, aged 40-75.
      RESULTS: Seventy-six percent of women ages 40 and over had had at least one
      mammogram, and most had had a clinical breast examination (88%) and Pap smear
      (89%). Rates were significantly lower for non-English-speaking Latinas and
      Chinese women (56 and 32%, respectively, for mammography), and maintenance
      screening (three mammograms in the past 5 years) varied from 7% (non-English
      speaking Chinese) to 53% (Blacks). Pap smear screening in the past 3 years was
      low among non-English-speaking Latinas (72%) and markedly lower among non-English
      speaking Chinese women (24%). The strongest predictors of screening behavior were
      having private health insurance and frequent use of medical services. Having a
      regular clinic and speaking English were also important. Race/ethnicity,
      education, household income, and employment status were, overall, not significant
      predictors of screening behavior. CONCLUSIONS: These baseline results support the
      importance of cancer screening interventions targeted to persons of foreign
      origin, particularly those less acculturated.

PMID- 11522162
TI  - Stability in consumption of fruit, vegetables, and sugary foods in a cohort from
      age 14 to age 21.
AB  - BACKGROUND: Eating behavior is an etiologic factor in the development of
      lifestyle-related diseases. Knowledge about the stability of eating behavior
      during the transition from adolescence to early adulthood has implication for
      dietary interventions for children and young adolescents. METHOD: Dietary data
      were collected by means of a short food frequency questionnaire as part of a
      Norwegian longitudinal cohort study on health behavior, lifestyle, and self
      reported health of adolescents. Of 885 14-year-old baseline participants, 521 21
      year-olds participated and 40% completed all surveys at each time point. RESULTS:
      Mean weekly frequency of consumption of fruit and vegetables decreased by 1-2.5
      times per week between ages 14 and 21, whereas that of sugar-containing soft
      drinks increased by almost 1 time per week between ages 15 and 16. Tracking of
      consumption patterns into young adulthood was seen for all four foods (P < 0.05
      for differences in means between the tracking groups). The proportions of
      individuals remaining in the same tracking categories at the major transition
      stages were 50-70%. Yet, some changed in the opposite direction of the observed
      trends. CONCLUSIONS: Despite the overall changes in mean weekly frequency of
      consumption and prevalence of daily consumers, relative ranking by frequency at
      age 14 indicated some stability of eating behavior into young adulthood.

PMID- 11522161
TI  - A randomized trial of a brief intervention to increase fruit and vegetable
      intake: a replication study among callers to the CIS.
AB  - BACKGROUND: Results are reported from a large randomized trial designed to
      increase fruit and vegetable consumption among callers to the National Cancer
      Institute's Cancer Information Service (CIS) (n = 1,717). METHODS: CIS callers
      assigned to the intervention group (n = 861) received a brief proactive
      educational intervention over the telephone at the end of usual service, with two
      follow-up mailouts. Key educational messages and print material derived from the
      NCI 5 A Day for Better Health program were provided to intervention participants.
      Participants were interviewed by telephone at 4 weeks (n = 1,307), 4 months (n =
      1,180), and 12 months for follow-up (n = 1,016). RESULTS: Results obtained from a
      single-item measure of fruit and vegetable consumption indicate a significant
      intervention effect of 0.88 servings per day at 4 weeks follow-up (P < 0.001),
      0.63 servings per day at 4 months follow-up (P < 0.001), and 0.43 servings per
      day at 12 months follow-up (P < 0.001). Using a 7-item food frequency measure, an
      intervention effect of 0.63 servings per day was obtained at 4 weeks follow-up (P
      < 0.001), compared with 0.39 servings per day at 4 months follow-up (P = 0.002)
      and 0.44 servings per day at 12 months follow-up (P = 0.002). A 24-h recall
      assessment included in the 4-month interviews also yielded a significant
      intervention effect of 0.67 servings per day (P = 0.015). The vast majority of
      callers (90%) endorsed the strategy of providing 5 A Day information proactively
      within the CIS. CONCLUSIONS: This brief educational intervention was associated
      with higher levels of self-reported fruit and vegetable intake at both short- and
      long-term follow-up. Additional research is recommended to test this or a similar
      intervention in diverse populations.

PMID- 11522164
TI  - Two-stage reconstruction of bilateral alveolar cleft using Y-shaped anterior
      based tongue flap and iliac bone graft.
AB  - OBJECTIVE: When an alveolar cleft is too large to close with adjacent mucobuccal
      flaps or large secondary fistula following a primary bilateral palatoplasty
      exists, a one-stage procedure for bone grafting becomes challenging. In such a
      case, we have used the tongue flap to repair the fistula and cleft alveolus
      followed by bone grafting to the cleft defect performed several months later. The
      purpose of this article is to report on our experiences with the use of an
      anteriorly based Y-shaped tongue flap to fit the palatal and labial alveolar
      defects and on the ultimate result of the bone graft. PATIENTS: A series of 14
      patients were treated with this approach from January 1994 to December 1998. The
      average age of the patients was 15.8 years (range 5 to 28 years). The mean period
      of follow-up following the second stage bone graft operation was 45.9 months
      (range 9 to 68 months). In 9 of the 14 patients, the long-fork type of a Y-shaped
      tongue flap was used for extended coverage of the labial-side alveolar defects
      with the palatal fistula; in the remaining patients, the short-forked design was
      used. RESULTS: All patients demonstrated a good clinical result after the initial
      repair of cleft alveolus and palatal fistula. There was no fistula recurrence,
      although partial necrosis of distal margin in long-forked tongue flap occurred in
      one patient. Furthermore, the bone graft, which was performed an average of 8
      months after the tongue flap repair, was always successful. Occasionally,
      transferred tongue tissue bulging interfered with the hygienic care of nearby
      teeth; however, these problems could be solved with proper contour-plasty
      performed afterward. No donor site complications such as sensory disturbance,
      change in taste, limitations in tongue movement, normal speech impairments, or
      tongue disfigurement were encountered. CONCLUSION: This two-stage reconstruction
      of a bilateral cleft alveolus using a Y-shaped tongue flap and iliac bone graft
      was very successful. It may be indicated for a bilateral cleft alveolus patient
      in which the direct closure of the cleft defect with adjacent tissue or the
      buccal flap is not easy because of scarred fibrotic mucosa and accompanied
      residual palatal fistula.

PMID- 11522163
TI  - Magnetic resonance imaging in the evaluation of occult submucous cleft palate.
AB  - OBJECTIVE: To explore the application of magnetic resonance imaging (MRI) in the
      evaluation of patients with occult submucous cleft palate and to use the MRI
      information obtained to aid in the treatment decision to perform surgery versus
      behavioral speech therapy. DESIGN: Prospective study with magnetic resonance (MR)
      images of subjects suspected of having occult submucous cleft palate. SETTING:
      Hospital and university-based. PATIENTS: Two girls who were 4 years old at the
      time of palatal surgery. INTERVENTION: Furlow double-opposing Z-plasty. MAIN
      OUTCOME MEASURES: MR images and clinical speech evaluations. RESULTS: MR images
      provided evidence of an interruption of levator veli palatini muscle tissue in
      the midline and a substantial attachment of levator muscle tissue to the
      posterior border of the hard palate. In addition, MR images for both subjects
      demonstrated remarkably similar bilateral encapsulating sheaths that contained
      nonmuscular tissue, as confirmed subsequently during surgery. The encapsulating
      sheaths interrupted the normal progression of the levator muscle sling across the
      midline. The MR images led to the decision to perform surgery instead of speech
      therapy. Hypernasality was markedly reduced in both subjects after surgery.
      CONCLUSIONS: MRI is an effective technique for diagnosing occult submucous cleft
      palate and may be an important aid in the treatment decision regarding surgery
      versus behavioral speech therapy for patients diagnosed with occult submucous
      cleft palate.

PMID- 11522165
TI  - Morphological characterization of the levator veli palatini muscle in children
      born with cleft palates.
AB  - OBJECTIVE: The aim of this study was to analyze, morphologically and
      biochemically, one of the soft palate muscles, the levator veli palatini (LVP),
      in children born with cleft palate. SUBJECTS AND METHODS: Biopsies were obtained
      from nine male and three female infants in connection with the early surgical
      repair of the hard and soft palate. Samples from five adult normal LVP muscles
      were used for comparison. The muscle morphology, fiber type and myosin heavy
      chain (MyHC) compositions, capillary supply, and content of muscle spindles were
      analyzed with different enzyme-histochemical, immunohistochemical, and
      biochemical techniques. RESULTS: Compared with the normal adult subjects, the LVP
      muscle from the infantile subjects with cleft had a smaller mean fiber diameter,
      a larger variability in fiber size and form, a higher proportion of type II
      fibers, a higher amount of fast MyHCs, and a lower density of capillaries. No
      muscle spindles were observed. Moreover, one-third of the biopsies from the
      infantile subjects with cleft LVP either lacked muscle tissue or contained only a
      small amount. CONCLUSIONS: The LVP muscle from children with cleft palate has a
      different morphology, compared with the normal adult muscle. The differences
      might be related to different stages in maturation of the muscles, changes in
      functional demands with growth and age, or a consequence of the cleft. The lack
      of contractile tissue in some of the cleft biopsies offers one possible
      explanation to a persistent postsurgical velopharyngeal insufficiency in some
      patients, despite a successful surgical repair.

PMID- 11522166
TI  - Change in levator veli palatini muscle activity of normal speakers in association
      with elevation of the velum using an experimental palatal lift prosthesis.
AB  - OBJECTIVE: The purpose of this study was to examine whether mechanical elevation
      of the velum can directly affect the levator veli palatini muscle (LVP) activity
      using normal speakers as subjects. DESIGN: Each subject was instructed to produce
      /mu/, /u/, /pu/, /su/, and /tsu/ in a speech task and to blow with maximum
      possible effort. Smoothed electromyographic activity of the LVP was recorded with
      an experimental palatal lift prosthesis (PLP) both in place and removed.
      PARTICIPANTS: Four normal speakers were used as subjects. RESULTS: LVP activity
      for all tasks was significantly smaller (p <.001; Student's t test) with the PLP
      in place than without the PLP for all subjects. An analysis of variance (p <.001)
      clarified that activity ranges of the LVP were significantly different between
      the removal and placement conditions for all the subjects. CONCLUSION: The result
      was similar to that previously obtained for patients with velopharyngeal
      incompetence wearing a PLP. It is possible that the decrease in the LVP activity
      in association with placement of a PLP is caused by the direct effect of
      mechanical elevation, which decreases the distance the velopharyngeal mechanisms
      must travel for complete closure of the velopharynx.

PMID- 11522168
TI  - Lip movement in patients with a history of unilateral cleft lip.
AB  - OBJECTIVE: The influence of a repaired cleft lip on the stability of coordination
      between upper and lower lip in nonspeech and speech tasks was investigated.
      DESIGN: First, we looked at the effects of a secondary cleft lip repair in three
      individuals. Second, we compared subjects with a history of repaired unilateral
      cleft lip and subjects with no history of cleft lip (controls). Lip coordination
      was measured using continuous estimates of relative phase. PARTICIPANTS: Subjects
      were nine children and adolescents with a primary unilateral cleft lip and palate
      repair and 4 participants without cleft matched for age across different age
      categories. RESULTS: In general, the averaged relative phase angle (RPA) angle
      values were smaller than 180 degrees, indicating an upper lip lead for lip
      closure. Controls showed a tendency toward a more symmetric type of coordination
      (close to 180 degrees), compared with subjects with a repaired unilateral cleft
      lip. The controls also showed less variation in coordination between the lips.
      For the more complex speech tasks, a general increase in variability of the RPA
      values for all subjects was observed, most likely suggesting a more flexible type
      of coordination. Regarding the effect of a secondary cleft lip repair, only one
      of the three patients showed a clearly less symmetric and less stable type of
      coordination, compared with preoperation results. CONCLUSIONS: There appear to be
      differences in lip coordination between speakers without and speakers with a
      repaired unilateral cleft lip. Furthermore, it seems that the stability of lip
      coordination tends to increase with age.

PMID- 11522167
TI  - Analysis of speech characteristics in children with velocardiofacial syndrome
      (VCFS) and children with phenotypic overlap without VCFS.
AB  - OBJECTIVE: To address two questions of theoretical importance regarding the
      profile and course of communication impairment associated with velocardiofacial
      syndrome (VCFS): (1) do speech characteristics of children with VCFS differ from
      a group of children with some of the phenotypic characteristics of VCFS who do
      not have the syndrome, and (2) do younger children with VCFS demonstrate speech
      patterns that differ from older children with VCFS? DESIGN: Prospective, cross
      sectional study comparing two groups of children at two age levels. PATIENTS:
      Thirteen children with VCFS and eight children with some of the phenotypic
      features of VCFS who did not have the syndrome. Children ranged in age from 3 to
      10 years. MAIN OUTCOME MEASURE: (1) Broad phonetic transcription of speech
      yielding measures of number of consonant types, Percent Consonant Correct, and
      percentage of glottal stops used; and (2) composite ratings of velopharyngeal
      function made from perceptual, aerodynamic, and endoscopic evaluations. RESULTS:
      Younger children with VCFS demonstrated greater speech impairment than older
      children with VCFS or the children without VCFS, such as smaller consonant
      inventories, greater number of developmental errors, greater severity of
      articulation disorder, and higher frequency of glottal stop use. The relationship
      between ratings of velopharyngeal function and the speech variables analyzed was
      not straightforward. CONCLUSIONS: Some young children with VCFS demonstrated
      speech impairment that is qualitatively and quantitatively different from older
      children with VCFS or children without VCFS. This finding supports the hypothesis
      that some children with VCFS demonstrate a profile of speech production that is
      different from normal but also may be specific to the syndrome.

PMID- 11522169
TI  - Nasal morphology and shape parameters as predictors of nasal esthetics in
      individuals with complete unilateral cleft lip and palate.
AB  - OBJECTIVE: The purpose of this study was to assess the ability of shape
      parameters of nasal morphology to predict esthetics in individuals with complete
      unilateral cleft lip and palate (CUCLP). METHODS: This retrospective study
      involved 28 patients with repaired CUCLP. Nostril morphology was analyzed using
      nose casts and a video-imaging technique. Calculated shape parameters included
      area, perimeter, centroid, angle of the principal axis, major and minor moments
      of area, anisometry, bulkiness, lateral offset, and three-dimensional
      internostril angles. Esthetics was assessed using a panel of six orthodontists
      who rated nasal esthetics from frontal, lateral, basal, and three-quarters view
      slides and from nose casts. Correlations between esthetics and the shape
      parameters were completed using the entire group as well as using two
      statistically determined subsets: those with the best and those with the worst
      esthetics. RESULTS: Nasal esthetics was related to only the perimeter and
      bulkiness parameter ratios. Symmetry of the perimeters between the right and left
      nostrils positively correlated with better esthetics using the entire sample
      group while symmetry of bulkiness between the right and left nostrils positively
      correlated with better esthetics using both the entire sample group and the best
      and worst subsets. CONCLUSIONS: Only perimeter and bulkiness showed positive
      correlations with nasal esthetics. The group of parameters used to assess nostril
      morphology had neither significant correlation with-nor predictive power for
      esthetics. Thus, an assessment of the entire nasal surface topography in three
      dimensions needs to be completed and assessed with respect to predictability of
      nasal esthetics.

PMID- 11522170
TI  - Phenotypic and molecular analyses of A/WySn mice.
AB  - OBJECTIVE: Since its first description, the A strain of mice have been utilized
      extensively as models to study the processes involved in clefting of the
      midfacial region. Of the A substrains, the A/WySn has a spontaneous rate of
      clefting of the lip of about 20% to 30%. The A/WySn mouse model was utilized in
      this study to analyze and compare the phenotypic and molecular changes in the
      midfacial region of embryos with and without cleft. RESULTS: Scanning electron
      microscopy and skeletal and cartilage preparations of newborn A/WySn pups showed
      the presence of bilateral and unilateral clefts of the lips and the disruption of
      the skeletal and cartilaginous components of the mice with clefts of the lip. The
      expression of the msx1 homeobox gene was analyzed by whole mount in situ
      hybridization of A/WySn embryos at different stages of midfacial development. The
      results showed that there was misregulation of the expression of the msx1 gene in
      embryos with cleft, with a persistence of expression in the distal growing tips
      of the midfacial processes and in areas that have fused in normal embryos without
      cleft. CONCLUSIONS: Although the genetic defect in A/WySn mice is not known, a
      possible candidate gene has been mapped to a corresponding human chromosome
      carrying retinoic acid receptor alpha, and there exists a possibility that msx1
      is in the same genetic pathway affected by the mutation of the gene in A/WySn.

PMID- 11522171
TI  - Histological investigation of the palatine bone in prenatal trisomy 21.
AB  - OBJECTIVE: The purpose of the present study was to investigate the horizontal
      part of the palatine bone in palates from human fetuses with trisomy 21 to
      improve the phenotypic classification of the genotypic anomaly. METHODS: Material
      from 23 human trisomy 21 fetuses was included in the study. The crown rump
      lengths of the fetuses ranged from 80 mm to 190 mm, corresponding to about 12 to
      21 weeks of gestational age. The material was examined histologically. RESULTS
      AND CONCLUSIONS: Histological examination demonstrated four different palatal
      phenotypes on the basis of the development of the horizontal part of the palatine
      bone: type I, palatine bone complete; type II, the mesial region of the
      horizontal part of the palatine bone is lacking; type III, complete absence of
      the horizontal part of the palatine bone; and type IV, auxiliary bones in the
      region of the transpalatine suture. This finding shows that different types of
      malformations may occur in the horizontal part of the palatine bone in human
      trisomy 21 fetuses.

PMID- 11522172
TI  - The prevalence of anomalies of the upper cervical vertebrae in subjects with
      cleft lip, cleft palate, or both.
AB  - OBJECTIVE: The purpose of this study was to examine the prevalence of cervical
      vertebral anomalies in individuals with cleft palate only (CPO) and bilateral
      (BCLP) and unilateral (UCLP) complete cleft lip and palate and make a comparison
      with a group without cleft. SETTING: This retrospective comparison was performed
      at the Dental Unit, Department of Plastic Surgery, National Hospital and at the
      Department of Orthodontics, Faculty of Dentistry, University of Oslo, Oslo,
      Norway. MATERIAL AND METHODS: Six hundred eleven subjects (334 boys, 277 girls)
      with three different cleft subtypes at age 6 years or older and 264 children (121
      boys, 143 girls) without clefts were included in this study. Their lateral
      cephalometric radiographs were studied for cervical vertebral anomalies and
      categorized into posterior arch deficiencies or fusions. RESULTS: In the total
      cleft sample, 111 subjects (18.2%) had cervical vertebral anomalies; of these, 10
      subjects had more than one anomaly. Posterior arch deficiency was found in 7.7%
      and fusions in 12.1%. In the sample without cleft, 9.1% had cervical vertebral
      anomalies, 5% posterior arch deficiency, and 4.1% fusions. When the cleft sample
      was divided into the three cleft subtypes, the prevalence of cervical vertebral
      anomalies was 25.6% in the CPO group, 16.3% in the BCLP group, and 11.1% in the
      UCLP group. Differences were statistically significant between the CPO and the
      group without cleft for both posterior arch deficiency and fusion anomalies (p
      <.01). CONCLUSION: Cervical vertebral anomalies occur more frequently in
      individuals with clefts as compared with those without clefts. This was
      statistically significant for the CPO group.

PMID- 11522173
TI  - Pure ectodermal dysplasia: retrospective study of 16 cases and literature review.
AB  - OBJECTIVE: To review the possible craniomaxillofacial deformative consequences
      associated with ectodermal dysplasias and embryonic malformations, which include
      dental ageneses. SETTING: Oral and Maxillofacial Surgery Department, University
      Hospital, Lille, France. PATIENTS: Sixteen patients (seven boys and nine girls,
      aged 4 to 34 years) with pure ectodermal dysplasia (no ectodermal dysplasia
      syndromes). INTERVENTIONS: All patients had a clinical examination. Seven (two
      boys and five girls, aged 4 to 25 years) had undergone plaster casts and
      radiographic and Delaire's cephalometric studies before being treated. MAIN
      OUTCOME MEASURES: All patients had tooth ageneses (from hypodontia to anodontia),
      associated with cutaneous dyshidrosis and hair and nail dystrophy. Most of them
      had a short face, with an unusual facial concavity, a maxillary retrusion, and a
      relative mandibular protrusion. MANAGEMENT RESULTS AND DISCUSSION: Depending on
      their ages and their orthopedic abnormalities, patients underwent either dental
      or prosthodontic, orthodontic, orthopedic, orthognathic, or implant treatment. So
      as not to interfere with the growth pattern, we preferred to reserve implant and
      orthognathic surgery for full-grown cases. CONCLUSIONS: Oral and maxillofacial
      surgeons must undertake a comprehensive approach to these patients to improve
      their dental, masticatory, growing, and orthognathic conditions.

PMID- 11522174
TI  - The effects of lactation education and a prosthetic obturator appliance on
      feeding efficiency in infants with cleft lip and palate.
AB  - OBJECTIVE: This prospective study examined the effect of lactation instruction
      and palatal obturation in decreasing time to feed, increasing intake, and on
      growth in eight breast milk bottle-fed newborn infants with cleft lip, cleft
      palate, or both. DESIGN: An A, B1, C1, B2, and C2 reversal design was used with
      eight mothers. In A, baseline data on minutes fed by breast were recorded. In B1,
      baseline on minutes fed with a Haberman bottle was recorded. In C1, minutes fed
      following lactation education and palatal obturation were documented. Lactation
      education was information given to mothers to recognize infant feeding cues and
      to have infant-led feedings. The palatal obturator was a passive molding
      appliance. In B2, the obturator was removed and minutes fed noted. In C2, the
      obturator was returned and lactation support provided. Mothers kept feeding logs,
      satisfaction was assessed, and infant breast milk intake and flow rate were
      recorded during each study phase. Routine nutrition evaluation of weight, height,
      weight for height, and feed volume was completed by a registered dietitian during
      and following completion of the study. RESULTS: Feeding times decreased with all
      infants, volume consumed increased with seven of eight infants, and flow rate
      increased with all infants. Mean feeding times during B1 and B2 phases (Haberman
      bottle only) were 34.4 and 32.3 minutes, respectively. Mean feeding times during
      C1 and C2 phases (obturation and lactation education) were 15.1 and 15.6 minutes.
      Volume of milk consumed during B1 and B2 feedings averaged 36.5 and 37 mL,
      compared with 67 mL and 76 mL during C1 and C2 phases. Growth as measured by
      height, weight gain, and weight for height during the study and the first 2 years
      of life compared favorably with that of children born without clefts.
      CONCLUSIONS: The combined use of a palatal obturator and lactation education
      reduced feeding time and increased volume intake and was associated with good
      growth. Mothers who had desired to breast-feed elected to use the obturator to
      support high-volume intake, decrease infant fatigue, and provide breast milk for
      nutrition.

PMID- 11522175
TI  - The oral health of children with clefts of the lip, palate, or both.
AB  - OBJECTIVE: The purpose of this study was to assess the prevalence of dental
      caries, developmental defects of enamel, and related factors in children with
      clefts. DESIGN: This cross-sectional prevalence study used standard dental
      indices for assessment. SETTING: Children underwent a dental examination under
      standard conditions of seating and lighting in the outpatient department of a
      dental hospital as part of an ongoing audit to monitor clinical outcomes.
      PARTICIPANTS: Ninety-one children aged 4, 8, and 12 years were included in the
      study. OUTCOME MEASUREMENTS: Dental caries were assessed by use of the decayed,
      missing, and filled index for primary teeth (dmft); Decayed, Missing, and Filled
      index for permanent teeth (DMFT) according to the criteria as used in the
      national survey of children's dental health in the United Kingdom. Developmental
      defects were assessed using the modified Developmental Defects of Enamel Index
      (Clarkson and O'Mullane, 1989). Dental erosion was assessed using the criteria
      derived for the national survey of children's dental health. RESULTS: Caries
      prevalence increased with age; 63% of patients at 4 years and 34% at 12 years
      were caries free. The mean dmft for the 4-year-olds was 1.3 with a mean DMFT for
      the 12-year-olds of 1.8. All the 4-year-olds had evidence of erosion of enamel in
      the primary teeth (incisors and first molars) and 56% of the 12-year-olds had
      erosion of permanent teeth (incisors and first permanent molars). Developmental
      defects of enamel became more prevalent with age, with at least one opacity in
      56% of 4-year-olds and 100% of 12-year-olds. Hypoplasia was not found in the
      primary dentition but affected permanent teeth in 38% of 8-year-olds and 23% of
      the 12-year-olds. CONCLUSION: This study has shown that dental disease is
      prevalent in these patients. These assessments not only provide a baseline on
      oral health parameters in young people with clefts but underline the need for a
      more aggressive approach to prevention of oral disease to optimize clinical
      outcome.

PMID- 11522176
TI  - The Tessier number 5 cleft with associated extremity anomalies.
AB  - OBJECTIVE: Oblique facial clefts are rare congenital deformities. They constitute
      0.22% of all facial malformations. In this case report, an oblique facial cleft
      defined as Tessier number 5 is presented. The number 5 cleft of Tessier is one of
      the most rare congenital facial clefts; review of the literature revealed 20
      patients. This case was also demonstrated with associated limb anomalies,
      suggesting that the patient may have been affected by the amnion rupture
      sequence. The teratology of these malformations is discussed, and attention is
      drawn to the amniotic rupture sequence as a possible cause.

PMID- 11522177
TI  - The faith of a coronal suture grafted onto midline synostosis inducing dura and
      deprived from tensile stress.
AB  - OBJECTIVE: To discuss possible reasons for the synostosis of a coronal suture
      that was transplanted onto synostosis inducing dura in a scaphocephalic human
      cranium. DESIGN: Case report. SETTING: Supraregional teaching hospital, center
      for craniofacial anomalies. PATIENT: A bathmocephalic boy, followed from age
      7(1/2) to 26 months. INTERVENTION: Radical synostosectomy, radial osteotomies in
      the parietal bone with outward fracturing of the barrel staves, and left-sided
      coronal suture transplantation onto the midline was undertaken at the age of 11
      months. METHODS: Computer tomography and clinical follow-up. RESULTS: The sutural
      graft, initially deprived from tensile stress and quickly exposed to the
      anomalous dura, turned synostotic in one year. CONCLUSIONS: Both cell signaling
      and biomechanical theories on calvarial morphogenesis, sutural development, and
      synostosis can apply. An animal experiment is recommended to test which
      hypothesis prevails.

PMID- 11522178
TI  - Single-follicular-unit hair transplantation to correct cleft lip moustache
      alopecia.
AB  - OBJECTIVE: To present the case of an 18-year-old boy with a cleft lip scar and an
      obligatory need for facial hair who underwent single-follicular-unit graft hair
      transplantation that resulted in significant moustache hair restoration in a
      single procedure. SETTING: The surgery was performed in an outpatient private
      practice setting using oral sedation and local anesthesia. RESULTS: Advances in
      instrumentation technology and an increased understanding of the anatomical
      clustering of hair follicles into so-called "follicular units" containing one to
      six hairs per unit has resulted in a rapid expansion of hair restoration surgery
      into new areas including female-pattern alopecia, scarring alopecias, and
      cosmetic surgery scars. These new techniques can be employed to create natural
      looking hair lines in front of artificial hair replacement systems; to improve
      unnatural looking, old "large-plug" hair transplants; and to correct
      discontinuity of eyebrows and hairlines in patients with congenital facial
      clefts. Increased awareness is needed to incorporate follicular-unit graft hair
      transplant surgery into the family of corrective surgery subspecialties.

PMID- 11522179
TI  - Do HIV type 1 RNA levels provide additional prognostic value to CD4(+) T
      lymphocyte counts in patients with advanced HIV type 1 infection?
AB  - Our objective was to assess whether HIV-1 RNA levels provide additional
      prognostic information beyond CD4(+) T lymphocyte counts in the prediction of
      subsequent HIV-1 disease progression among patients with advanced HIV-1 disease.
      In a nested case-control study conducted in patients with baseline CD4(+) T
      lymphocyte counts < 300 cells/mm(3) and receiving nucleoside reverse
      transcriptase inhibitors, 102 patients who progressed to an AIDS-defining event
      or death were matched within 10 CD4(+) T lymphocyte cells/mm(3) to patients who
      did not progress. The relationship between plasma HIV-1 RNA levels and HIV-1
      disease progression was studied using conditional logistic regression analysis,
      which adjusts for the matching by baseline CD4(+) T lymphocytes. We observed a
      0.10 log(10) copies/ml difference in baseline HIV-1 RNA levels between cases and
      their matched controls (p = 0.027). The relative risk for HIV-1 disease
      progression increased with increasing baseline HIV-1 RNA levels (odds ratio [OR]
      for a 3-fold higher HIV-1 RNA level, 1.42; 95% confidence interval [CI], 1.08-
      1.86), and remained important when also controlling for clinical status at
      baseline and CD4(+) T lymphocytes at 2 months (p = 0.038). Higher baseline HIV-1
      RNA levels were associated with HIV-1 disease progression among patients with a
      baseline CD4(+) T lymphocyte count of 100 cells/mm(3) or greater (OR, 1.80; 95%
      CI, 1.15--2.81), but not among patients with a baseline CD4(+) T lymphocyte count
      < 100 cells/mm(3) (OR, 1.09; 95% CI, 0.73--1.63). We concluded that HIV-1 RNA
      levels predict subsequent HIV-1 disease progression independent of CD4(+) T
      lymphocyte counts. The magnitude and importance of the prognostic information
      contained in the HIV-1 RNA levels appear to depend on the CD4(+) T lymphocyte
      counts.

PMID- 11522181
TI  - Metabolic abnormalities in HIV type 1-infected children treated and not treated
      with protease inhibitors.
AB  - Our objective was to determine whether HIV-infected children treated with
      protease inhibitors (PIs) have different blood lipid, insulin, and glucose levels
      and body composition than HIV-infected children not treated with PIs. A cross
      sectional cohort study was performed; in which 23 children were treated with
      combination antiretroviral therapy including a PI for at least 6 months and 12
      children were treated with nucleoside reverse transcriptase inhibitors only (no
      PI group). Levels of lipids, apolipoprotein B (apoB), insulin, and glucose were
      determined in the fasting state. Body composition and fat distribution were
      determined by anthropometric measurements and dual energy X-ray absorptiometry
      (DEXA) scan. Total cholesterol levels were higher in the PI-treated children
      (5.33 +/- 0.87 mM) than in the no-PI children (3.69 +/- 0.59 mM) (p < 0.0001).
      Similarly, low-density lipoprotein (LDL) levels were also elevated in the PI
      treated children (3.27 +/- 0.76 vs. 2.14 +/- 0.51 mM) (p < 0.0001). ApoB and high
      density lipoprotein (HDL), and to a lesser degree triglyceride levels, were also
      increased in the PI-treated children. Apart from percent arm fat as measured by
      DEXA, there were no differences between the two groups in measures of body
      composition or in their fasting glucose and insulin levels. The results from this
      cross-sectional cohort study suggest that the predominant lipid abnormalities
      associated with treatment with combination antiretroviral therapy including a PI
      in HIV-1-infected children are elevated total and LDL cholesterol.

PMID- 11522180
TI  - Thymidine analog and multinucleoside resistance mutations are associated with
      decreased phenotypic susceptibility to stavudine in HIV type 1 isolated from
      zidovudine-naive patients experiencing viremia on stavudine-containing regimens.
AB  - Studies have demonstrated that HIV-1 isolated from subjects experiencing
      virologic failure on stavudine (d4T)-containing regimens often contains thymidine
      analog mutations (TAMs), consisting of reverse transcriptase (RT) mutations M41L,
      D67N, K70R, L210W, T215Y/F, and K219Q/E, previously associated only with
      zidovudine (ZDV) resistance. In clinical study NZT40012, HIV-1 was isolated from
      86 ZDV-naive subjects experiencing viremia on d4T-based therapies (plasma HIV-1
      RNA > or =1000 copies/ml) and analyzed to examine the association between RT
      mutations and phenotypic resistance to d4T. Resistance-associated mutations were
      analyzed from HIV-1 isolated from 85 subjects. Of these, 24 samples (28%) had
      TAMs, and 30 samples (35%) had either TAMs and/or the Q151M multinucleoside
      resistance (MNR) mutation. Phenotypic susceptibility to d4T was determined by two
      commercially available methods. Statistically significant increases (p < 0.001)
      in phenotypic fold resistance to d4T were observed in virus with at least one TAM
      or MNR mutation. However, the mean increases in phenotypic resistance were 4-fold
      for the Antivirogram assay and 3-fold for the Phenosense HIV assay, only slightly
      above the levels used to designate decreased susceptibility to d4T. Subjects can
      experience viremia on d4T-containing regimens with virus exhibiting only small
      increases in IC(50), suggesting that relatively small changes in viral
      susceptibility to d4T may influence drug efficacy.

PMID- 11522182
TI  - HIV type 1 Tat inhibits tumor necrosis factor alpha-induced repression of tumor
      necrosis factor receptor p55 and amplifies tumor necrosis factor alpha activity
      in stably tat-transfected HeLa Cells.
AB  - The human immunodeficiency virus type 1 (HIV-1) Tat protein is a key regulatory
      protein in the HIV-1 replication cycle. Tat interacts with cellular
      transcriptional factors and cytokines, such as tumor necrosis factor (TNF-alpha),
      and alters the expression of a variety of genes in HIV-1-infected and noninfected
      cells. To further elucidate the mechanisms by which HIV-1 Tat amplifies the
      activity of TNF-alpha, we transfected the HIV-1 tat gene into an epithelial
      (HeLa) cell line. We observed that Tat-expressing cells had increased NF-kappa B
      dependent trans-activational activity due to enhanced NF-kappa B--DNA binding in
      response to TNF-alpha treatment. Tumor necrosis factor receptor (TNFR) p55 was
      the prominent receptor, as neutralizing antibodies to TNFR p55, but not to TNFR
      p75, blocked TNF-alpha-mediated NF-kappa B activation. Furthermore, tat
      transfected cells were more sensitive to TNF-alpha-induced cytotoxicity and only
      the neutralizing antibodies to TNFR p55 completely protected the cells. To
      determine whether TNFR p55 was involved in amplification of cellular response to
      TNF-alpha by HIV-1 Tat, we investigated the effect of TNF-alpha on TNFR p55
      expression in the tat-transfected cells. TNF-alpha treatment resulted in a
      reduction in both TNFR p55 mRNA and protein levels in the control cells but not
      in the tat-transfected cells as determined with Northern blot and Western blot
      analyses, respectively. Our results indicate that HIV-1 Tat may inhibit TNF-alpha
      induced repression of TNFR p55 and thereby amplify TNF-alpha activity in these
      stably transfected cells.

PMID- 11522183
TI  - HIV type 1 infection of human astrocytes is restricted by inefficient viral
      entry.
AB  - The mechanism by which HIV infects astrocytes is not known. We used the simian
      virus 40 (SV40)-transformed human astrocyte cell line, SVG-A, to investigate HIV
      infection of astrocytes. We previously reported that SVG-A cells are susceptible
      to low levels of CD4/CXCR4-independent infection by an X4 strain of HIV-1.
      Infection was greatly increased when the prototypical X4 receptors, CD4 and
      CXCR4, were expressed on the SVG-A cells (SVGCD4-X4). These data suggest that HIV
      1 enters astrocytes by a novel mechanism that is inefficient compared with
      CD4/CXCR4-mediated entry. In this article, we report high levels of early viral
      gene expression in both SVG-A and SVGCD4-X4 cells once the HIV entry pathway is
      circumvented. These data indicate that HIV-1 infection of SVG-A cells is
      restricted by inefficient viral entry rather than by post-entry events. As we
      were unable to detect infection of nontransformed primary astrocytes, we
      investigated whether SV40 transformation affects the susceptibility of astrocytes
      to HIV infection. To study this, we transformed primary fetal and adult
      astrocytes with the same origin-defective SV40 mutant that was used to transform
      the SVG-A cell line. We found that SV40 transformation did not alter the
      susceptibility of astrocytes to HIV infection. Furthermore, high levels of early
      viral gene expression were detected in these cells once the HIV entry process was
      by-passed. Taken together, the results of these studies indicate that HIV
      infection of human astrocytes is restricted by inefficient viral entry.

PMID- 11522184
TI  - Natural infection of wild-born mandrills (Mandrillus sphinx) with two different
      types of simian immunodeficiency virus.
AB  - We found a novel primate lentivirus in mandrill (Mandrillus sphinx). To clarify
      the evolutionary relationships and transmission patterns of human/simian
      immunodeficiency virus (HIV/SIV), we screened blood samples from 30 wild-born
      healthy Cameroonian mandrills. Five (16.7%) of them were seropositive for SIV.
      Three SIV strains were isolated from the five seropositive mandrills by
      cocultivation of their peripheral blood mononuclear cells (PBMCs) with PBMCs of
      rhesus macaques, a human T cell line (M8166), and/or a cynomolgus macaque T cell
      line (HSC-F). One of the newly isolated SIV strains was intravenously inoculated
      into two rhesus macaques and resulted in chronic infection. In the SIV-infected
      macaques at 45 weeks after inoculation, we observed a mild decline in the number
      of peripheral CD4(+) lymphocytes, lymphadenopathy, and blastic follicular
      dendritic cells with mild follicular hyperplasia in the peripheral lymph nodes. A
      phylogenetic analysis based on the pol sequence showed that the newly found SIVs
      from Cameroonian mandrills did not cluster with SIVmndGB1, which is the former
      representative strain of SIVmnd. The SIVmnds from Cameroon formed a new,
      independent lineage that branched before the root of the HIV-1/SIVcpz lineage
      with 996 of 1000 bootstrap replications. They clustered host specifically, and
      exhibited about 16.9% diversity at the level of nucleotide sequence among
      Cameroonian SIVmnd strains. These results indicate that the SIVmnds isolated in
      Cameroon are a novel type of SIVmnd and have infected Cameroonian mandrills for a
      long time. We therefore designated the Cameroonian SIVmnd as SIVmnd type 2 and
      redesignated SIVmndGB1 as SIVmnd type 1. To date, M. sphinx is the only primate
      species other than humans that is naturally infected with two different types of
      SIV.

PMID- 11522185
TI  - A divergent simian immunodeficiency virus from sooty mangabey with an atypical
      Tat-TAR structure.
AB  - SIVsm, the simian immunodeficiency virus that naturally infects sooty mangabeys
      in West Africa, is the closest lentiviral relative of human immunodeficiency
      virus type 2 (HIV-2). To determine the genetic characteristics of SIVsm in its
      natural host, we sequenced the full-length genome of SIVsmSL92b, a primary
      isolate obtained from a pet sooty mangabey in Sierra Leone. SIVsmSL92b proved to
      be the most divergent member of the HIV-2/SIVsm lineage found thus far, having as
      much as 35% nucleotide divergence from other HIV-2 genomes. A phylogenetic
      association between SIVsmSL92b and HIV-2 PA subtype E, which had been previously
      revealed by the analysis of partial gag sequences, was extended to the pol gene.
      SIVsmSL92b showed several divergent features, including a short Tat protein of
      104 residues and an atypical TAR structure. Specifically, only one of the
      duplicate TAR elements contained the conserved hexanucleotide loop sequence
      CUGGGX important for Tat-cyclin T1 binding. These features suggested that the
      mechanism of SIVsmSL92b Tat and TAR interaction differed from that described for
      HIV-2. Taken together, these findings indicated that the structural diversity
      within the HIV-2/SIVsm lineage was greater than previously appreciated.

PMID- 11522186
TI  - Tenofovir, adefovir, and zidovudine susceptibilities of primary human
      immunodeficiency virus type 1 isolates with non-B subtypes or nucleoside
      resistance.
AB  - New antiretroviral drugs with activity against strains of human immunodeficiency
      virus type 1 (HIV-1) with non-B subtypes and with resistance to current
      antiretroviral drugs are needed. The activity of two nucleotide analogs,
      tenofovir and adefovir (PMPA and PMEA, respectively), against non-B subtypes and
      nucleoside-resistant primary HIV-1 isolates was assessed. Tenofovir and adefovir
      were fully active against a panel of subtypes A, C, D, E, F, G, and group O
      primary HIV-1 isolates as compared with their respective activity against subtype
      B isolates. Moreover, the susceptibility of a panel of 10 primary HIV-1 isolates
      with >10-fold mean resistance to zidovudine, lamivudine, and abacavir was within
      2.2-fold of wild-type tenofovir susceptibility for each isolate. An oral prodrug
      of tenofovir, tenofovir disoproxil fumarate (DF), is currently in phase III
      clinical trials for the treatment of HIV-1 infection. These in vitro
      susceptibility results suggest that tenofovir DF may be active in vivo against
      HIV-1 with nucleoside resistance as well as against HIV-1 with non-B subtypes.

PMID- 11522187
TI  - HIV type 1 vaccine-induced T cell memory and cytotoxic T lymphocyte responses in
      HIV type 1-uninfected volunteers.
AB  - T cell memory to human immunodeficiency virus type 1 (HIV-1) antigens and anti
      HIV-1 cytotoxic T lymphocyte (CTL) activity were assessed after administration of
      live canarypox virus (ALVAC) expressing HIV-1 env, gag, and protease (vCP205)
      vaccine given alone, vCP205 given with SF-2 recombinant gp120 (rgp120) vaccine,
      and placebos at 0, 1, 3, and 6 months. Healthy, HIV-1-uninfected subjects
      reporting high-risk and low-risk behavior for HIV-1 were enrolled. Anti-HIV-1 Env
      CD8(+) CTLs (HIV-1(MN) and/or HIV-1 subtype B and C primary isolate sequences)
      were detected in 12 (60%) and anti-HIV-1 Gag CD8(+) CTLs in 7 (35%) of the 20
      vCP205 vaccine recipients tested by CTL assay 3.5 months after the final
      immunization. Fourteen days after the fourth immunization, lymphocyte
      proliferation in response to HIV-1 Gag antigen was detected in 14 (48%) of 29
      vCP205 vaccine recipients, but secreted cytokine levels to HIV-1 Gag antigen were
      not above unstimulated levels. Coadministration of SF-2 rgp120 vaccine with
      vCP205 vaccine enhanced lymphocyte proliferation in response to HIV-1 envelope
      glycoprotein and broadened the envelope-stimulated cytokine secretion pattern, so
      that it consisted of both Th1 and Th2 cytokines compared with only interferon
      gamma (IFN-gamma) after vCP205 vaccine given alone. There was a possible
      association between HIV-1 envelope glycoprotein-stimulated interleukin 2
      secretion and CD8(+) CTLs against HIV-1 envelope glycoprotein, and an inverse
      relation between lymphocyte proliferation and CTLs against HIV-1 Gag antigens.
      Thus, a durable anti-HIV-1 CD8(+) CTL response was detected after immunization
      with the live canarypox virus vaccine and preexisting helper T cell memory
      responses did not necessarily predict later CD8(+) CTL activity.

PMID- 11522188
TI  - Systemic and intestinal immune responses to HIV-2287 infection in Macaca
      nemestrina.
AB  - Nonhuman primate models of human AIDS have been used successfully to evaluate
      candidate vaccines and infection intervention therapies. Successes of
      pathogenicity studies in primate models have been limited because of the varied
      infection outcomes and characteristic low number of study animals. The acutely
      pathogenic HIV-2(287)--Macaca nemestrina model has shown promise both in
      antiviral drug evaluation and in pathogenicity studies. Here we describe virus
      replication, spread, and host responses during the first 28 days of HIV-2(287)
      infection. Focusing on 18 macaques from a larger 27-macaque study, we report
      changing virus loads, CD4(+) cell depletions, and antibody responses both
      systemically and in the mucosa of the small intestine. After intravenous
      inoculation, blood and intestinal tissue were collected from pairs of macaques at
      12 hr and 1, 2, 4, 6, 10, 14, 21, and 28 days postinfection. Specimens were
      examined for evidence of infection by quantitative cultures, in situ
      hybridization, lymphocyte subset monitoring, and antibody production. The data
      were presented serially as though all samples were collected from a single
      macaque. The highest blood virus loads were detected between days 10 and 14 and
      subsequently decreased through day 28. This coincided with a significant increase
      in ileum mucosa virus loads on day 10, which became undetectable by day 28. The
      lowest levels of CD4(+) cells were observed on days 21 and 28 in blood and ileum
      mucosa. CD4(+):CD8(+) cell ratios in blood and ileum dropped dramatically after
      day 10 to lowest levels by day 28. Intestinal virus loads were inversely
      correlated with CD4(+) cell and virus-specific antibody levels in the ileum after
      day 6. These results underscore the suitability of this model for pathogenicity
      studies as well as the importance of the intestinal lymphoid tissues as an
      initial site of virus replication and cell destruction during the acute,
      asymptomatic stage of AIDS development.

PMID- 11522189
TI  - Structural features of HIV envelope defined by antibody escape mutant analysis.
AB  - Two neutralizing antibodies specific for the V3 sequence of HIV envelope were
      used to generate escape variants from the HTLV(IIIB) founder virus. The full
      gp120 sequence of each variant was then analyzed to identify mutations
      responsible for immune escape. As predicted, most escape variants harbored amino
      acid changes in the V3 crown sequence. However, one variant differed from its
      founder only within the conserved C2 region. These findings, when analyzed in
      conjunction with crystallographic data, suggest a new three-dimensional model for
      HIV envelope folding, in which the V3 loop extends across the CD4-binding face of
      gp120 to associate with discontinuous C2 residues. This envelope configuration
      may provide an effective immune defense mechanism for HIV, as the highly variable
      residues of the V3 loop may shield conserved amino acids pertinent to viral
      infection.

PMID- 11522190
TI  - Full-length genome sequencing of HIV type 1 group O viruses isolated from a
      heterosexual transmission cluster in Senegal.
AB  - In a polygamous marriage in Senegal, the husband and his two spouses were
      infected with HIV-1 group O. This study provides new full-length genome sequences
      for the two spouses (99SE-MP1299 and 99SE-MP1300) and the 3'-end LTR-tat fragment
      (6084 bp) for the husband (98SE-42HALD). Phylogenetic tree and diversity plot
      analysis revealed that the new viruses belong to HIV-1 group O and that they are
      closely related to each other in a cluster around ANT-70. The intrafamilial
      transmission occurred at most 6 years ago. The interpatient variability was
      highest in the envelope region, and in some regions of the envelope the strains
      from the two spouses do not cluster together anymore. The source of infection was
      in Cameroon and confirms a slow but continuous spread of HIV-1 group O viruses.

PMID- 11522191
TI  - Molecular characterization of a highly divergent HIV type 1 isolate obtained
      early in the AIDS epidemic from the Democratic Republic of Congo.
AB  - Numerous complete human immunodeficiency virus type 1 (HIV-1) genomes have been
      characterized for contemporary viruses, but few isolates obtained early in the
      HIV-1 epidemic have been studied. In this article, we describe the molecular
      characterization of an HIV-1 isolate (83CD003) that was obtained from an AIDS
      patient in Kinshasa, Democratic Republic of Congo (DRC) in 1983. The complete
      83CD003 genome was sequenced in its entirety and found to encode uninterrupted
      open reading frames for all viral genes. Phylogenetic analysis revealed 83CD003
      was a member of the major (M) group of HIV -1, but did not group with any of the
      known subtypes. Rather, it formed an independent lineage in all regions of its
      genome that was roughly equidistant from representatives of all other subtypes.
      Similarly, 83CD003 also did not cluster with any of several unclassified group M
      sequences that have been reported more recently to circulate in the DRC,
      suggesting that it may represent an early group M lineage thai is either rare or
      has gone extinct. The molecular clone of 83CD003 yielded an infectious virus
      after transfection into mammalian cells and its biological properties can be
      further studied.

PMID- 11522192
TI  - Dynamic mimicry in an Indo-Malayan octopus.
AB  - During research dives in Indonesia (Sulawesi and Bali), we filmed a distinctive
      long-armed octopus, which is new to science. Diving over 24 h periods revealed
      that the 'mimic octopus' emerges during daylight hours to forage on sand
      substrates in full view of pelagic fish predators. We observed nine individuals
      of this species displaying a repertoire of postures and body patterns, several of
      which are clearly impersonations of venomous animals co-occurring in this
      habitat. This 'dynamic mimicry' avoids the genetic constraints that may limit the
      diversity of genetically polymorphic mimics but has the same effect of decreasing
      the frequency with which predators encounter particular mimics. Additionally, our
      observations suggest that the octopus makes decisions about the most appropriate
      form of mimicry to use, allowing it to enhance further the benefits of mimicking
      toxic models by employing mimicry according to the nature of perceived threats.

PMID- 11522194
TI  - Is the impact of environmental noise visible in the dynamics of age-structured
      populations?
AB  - Climate change has ignited lively research into its impact on various population
      level processes. The research agenda in ecology says that some of the
      fluctuations in population size are accountable for by the external noise (e.g.
      weather) modulating the dynamics of populations. We obeyed the agenda by assuming
      population growth after a resource-limited Leslie matrix model in an age
      structured population. The renewal process was disturbed by superimposing noise
      on the development of numbers in one or several age groups. We constructed models
      for iteroparous and semelparous breeders so that, for both categories, the
      population growth rate was matching. We analysed how the modulated population
      dynamics correlates with the noise signal with different time-lags. No
      significant correlations were observed for semelparous breeders, whereas for
      iteroparous breeders high correlations were frequently observed with time-lags of
      71 year or longer. However, the latter occurs under red-coloured noise and for
      low growth rates when the disturbance is on the youngest age group only. It is
      laborious to find any clear signs of the (red) noise- and age group-specific
      fluctuations if the disturbance influences older age groups only. These results
      cast doubts on the possibility of detecting the signature of external disturbance
      after it has modulated temporal fluctuations in age-structured populations.

PMID- 11522193
TI  - Patterns of coral-dinoflagellate associations in Acropora: significance of local
      availability and physiology of Symbiodinium strains and host-symbiont
      selectivity.
AB  - Like other reef-building corals, members of the genus Acropora form obligate
      endosymbioses with dinoflagellates (zooxanthellae) belonging to the genus
      Symbiodinium. Both Symbiodinium and its hosts are diverse assemblages, and the
      relationships between host and algal genotypes are unclear. In this study, we
      determined phylogenetic relationships between Symbiodinium isolates from a wide
      range of Acropora species and plotted the algal genotypes onto a molecular
      phylogeny of 28 Acropora species, using the same samples for the host and
      symbiont genotyping. In addition, we performed a preliminary survey of
      zooxanthella distribution in Acropora species from the central Great Barrier
      Reef. Three of the four known major zooxanthellae clades were represented in the
      168 samples examined, and within the major clade C, three distinct subclades were
      identified. No evidence was found for coevolution, but several clear patterns of
      specificity were identified. Moreover, composition of the zooxanthella pool
      varied among locales and in one host species we found light-related patterns of
      zooxanthella distribution.

PMID- 11522195
TI  - Genetic consequences of population decline in the European otter (Lutra lutra):
      an assessment of microsatellite DNA variation in Danish otters from 1883 to 1993.
AB  - The European otter (Lutra lutra) was common in Denmark until the 1960s, but its
      present distribution encompasses only a minor part of the country. The aim of
      this study was to assess whether the recent population decline has resulted in
      loss of genetic variability and to gain further insight into the dynamics of the
      population decline. This was done by analysing microsatellite DNA variation in
      contemporary and historical samples, the latter encompassing DNA samples
      extracted from museum specimens covering a time-span from the 1880s to the 1960s.
      Tests for differences in expected heterozygosity and the numbers of alleles in
      contemporary versus historical samples and a test for detecting population
      bottlenecks provided few indications of a recent bottleneck and loss of
      variability. However, a procedure for detecting population expansions and
      declines, based on the genealogical history of microsatellite alleles, suggested
      that a drastic long-term population decline has taken place, which could have
      started more than 2000 years ago, possibly due to ancient anthropogenic pressure.
      Finally, assignment tests and pairwise F(ST) values suggested weak but
      statistically significant genetic differentiation between the extant population
      and historical samples of otters from other regions in Denmark, more likely
      reflecting differentiation among original populations rather than recent drift.

PMID- 11522196
TI  - Separating the effects of predation risk and interrupted foraging upon mass
      changes in the blue tit Parus caeruleus.
AB  - The optimal amount of reserves that a small bird should carry depends upon a
      number of factors, including the availability of food and environmental predation
      risk levels. Theory predicts that, if predation risk increases, then a bird
      should maintain a lower level of reserves. Previous experiments have given mixed
      results: some have shown reduced reserves and some, increased reserves. However,
      the birds in these studies may have been interpreting a staged predation event as
      a period when they were unable to feed rather than a change in predation risk:
      theory predicts that, if the food supply within the environment is variable, then
      reserves should be increased. In the present study, we presented blue tits (Parus
      caeruleus) with a potential predator and compared this response (which could have
      been potentially confounded by perceived interruption effects) with a response to
      an actual interruption in the environment during both long and short daytime
      lengths. During long (but not short) days, the birds responded in line with
      theoretical predictions by increasing their reserves in response to interruption
      and reducing them in response to predation. These results are examined in the
      light of other experimental manipulations and we discuss how well experimental
      tests have tested the predictions made by theoretical models.

PMID- 11522197
TI  - The quality and isolation of habitat patches both determine where butterflies
      persist in fragmented landscapes.
AB  - Habitat quality and metapopulation effects are the main hypotheses that currently
      explain the disproportionate decline of insects in cultivated Holarctic
      landscapes. The former assumes a degradation in habitat quality for insects
      within surviving ecosystems, the latter that too few, small or isolated islands
      of ecosystem remain in landscapes for populations to persist. These hypotheses
      are often treated as alternatives, and this can lead to serious conflict in the
      interpretations of conservationists. We present the first empirical demonstration
      that habitat quality and site isolation are both important determinants of where
      populations persist in modern landscapes. We described the precise habitat
      requirements of Melitaea cinxia, Polyommatus bellargus and Thymelicus acteon, and
      quantified the variation in carrying capacity within each butterfly's niche. We
      then made detailed surveys to compare the distribution and density of every
      population of each species with the size, distance apart and quality of their
      specific habitats in all their potential habitat patches in three UK landscapes.
      In each case, within-site variation in habitat quality explained which patches
      supported a species' population two to three times better than site isolation.
      Site area and occupancy were not correlated in any species. Instead of
      representing alternative paradigms, habitat quality and spatial effects operate
      at different hierarchical levels within the same process: habitat quality is the
      missing third parameter in metapopulation dynamics, contributing more to species
      persistence, on the basis of these results, than site area or isolation. A
      reorientation in conservation priorities is recommended.

PMID- 11522198
TI  - Spatial Ultimatum Games, collaborations and the evolution of fairness.
AB  - It is often the case that individuals in a social group can perform certain tasks
      (such as hunting, for example) more efficiently if they collaborate with other
      individuals than if they act alone. In such situations one is necessarily faced
      with the problem of how the resource obtained as the result of such a
      collaboration should be divided among the collaborating individuals. If one of
      the individuals in the collaboration is in a position (through its dominance
      rank, for example) to impose a particular division of the resource on the other
      members of the collaboration then we show that an evolutionary dilemma arises
      which prevents such collaborations being evolutionarily stable. This dilemma,
      which is closely related to the well-known Ultimatum Game, results from the fact
      that in such situations natural selection favours individuals who, if dominant,
      offer smaller and smaller shares of the resource to the others and, if
      subdominant, will accept lower and lower offers. We also show, however, that this
      dilemma is naturally resolved in a spatially structured population with selection
      favouring the evolution of a fair division of the resource and consequently
      ensuring the evolutionary stability of collaborations of this type.

PMID- 11522199
TI  - The small world inside large metabolic networks.
AB  - The metabolic network of the catabolic, energy and biosynthetic metabolism of
      Escherichia coli is a paradigmatic case for the large genetic and metabolic
      networks that functional genomics efforts are beginning to elucidate. To analyse
      the structure of previously unknown networks involving hundreds or thousands of
      components by simple visual inspection is impossible, and quantitative approaches
      are needed to analyse them. We have undertaken a graph theoretical analysis of
      the E. coli metabolic network and find that this network is a small-world graph,
      a type of graph distinct from both regular and random networks and observed in a
      variety of seemingly unrelated areas, such as friendship networks in sociology,
      the structure of electrical power grids, and the nervous system of Caenorhabditis
      elegans. Moreover, the connectivity of the metabolites follows a power law,
      another unusual but by no means rare statistical distribution. This provides an
      objective criterion for the centrality of the tricarboxylic acid cycle to
      metabolism. The small-world architecture may serve to minimize transition times
      between metabolic states, and contains evidence about the evolutionary history of
      metabolism.

PMID- 11522200
TI  - Buoyant balaenids: the ups and downs of buoyancy in right whales.
AB  - A variety of marine mammal species have been shown to conserve energy by using
      negative buoyancy to power prolonged descent glides during dives. A new non
      invasive tag attached to North Atlantic right whales recorded swim stroke from
      changes in pitch angle derived from a three-axis accelerometer. These results
      show that right whales are positively buoyant near the surface, a finding that
      has significant implications for both energetics and management. Some of the most
      powerful fluke strokes observed in tagged right whales occur as they counteract
      this buoyancy as they start a dive. By contrast, right whales use positive
      buoyancy to power glides during ascent. Right whales appear to use their positive
      buoyancy for more efficient swimming and diving. However, this buoyancy may pose
      added risks of vessel collision. Such collisions are the primary source of
      anthropogenic mortality for North Atlantic right whales, whose population is
      critically endangered and declining. Buoyancy may impede diving responses to
      oncoming vessels and right whales may have a reduced ability to manoeuvre during
      free ascents. These risk factors can inform efforts to avoid collisions.

PMID- 11522201
TI  - Consequences of life history for inbreeding depression and mating system
      evolution in plants.
AB  - Many plants are perennial, but most studies of inbreeding depression and mating
      system evolution focus on annuals. This paper extends a population genetic model
      of inbreeding depression due to recessive deleterious mutations to perennials.
      The model incorporates life history and mating system variation, and
      multiplicative selection across many genetic loci. In the absence of substantial
      mitotic mutation, perennials have higher mean fitness and lower, or even
      negative, inbreeding depression than annuals with the same mating system. As in
      annuals, self fertilization exposes deleterious recessive mutations to selection,
      increasing mean fitness and decreasing inbreeding depression. Including mitotic
      mutation decreases mean fitness while increasing inbreeding depression.
      Perenniality introduces a kind of selective sieve, such that strongly recessive
      mutations contribute disproportionately to mean fitness and inbreeding
      depression. In the presence of high mitotic mutation, this selective sieve may
      provide a mechanistic basis for high inbreeding depression observed in some long
      lived perennials. Without substantial mitotic mutation, it is difficult to
      reconcile genetically based models of inbreeding depression with the empirical
      generalization that perennials outcross while related annuals self fertilize.

PMID- 11522202
TI  - Cryptic diversity in European bats.
AB  - Different species of bat can be morphologically very similar. In order to
      estimate the amount of cryptic diversity among European bats we screened the
      intra- and interspecific genetic variation in 26 European vespertilionid bat
      species. We sequenced the DNA of subunit 1 of the mitochondrial protein NADH
      dehydrogenase (ND1) from several individuals of a species, which were sampled in
      a variety of geographical regions. A phylogeny based on the mitochondrial (mt)
      DNA data is in good agreement with the current classification in the family.
      Highly divergent mitochondrial lineages were found in two taxa, which differed in
      at least 11% of their ND1 sequence. The two mtDNA lineages in Plecotus austriacus
      correlated with the two subspecies Plecotus austriacus austriacus and Plecotus
      austriacus kolombatovici. The two mtDNA lineages in Myotis mystacinus were
      partitioned among two morphotypes. The evidence for two new bat species within
      Europe is discussed. Convergent adaptive evolution might have contributed to the
      morphological similarity among distantly related species if they occupy similar
      ecological niches. Closely related species may differ in their ecology but not
      necessarily in their morphology. On the other hand, two morphologically clearly
      different species (Eptesicus serotinus and Eptesicus nilssonii) were found to be
      genetically very similar. Neither morphological nor mitochondrial DNA sequence
      analysis alone can be guaranteed to identify species.

PMID- 11522204
TI  - Decision rules, energy metabolism and vigour of hermit-crab fights.
AB  - Aggressive interactions between animals are often settled by the use of repeated
      signals that reduce the risk of injury from combat but are expected to be costly.
      The accumulation of lactic acid and the depletion of energy stores may constrain
      activity rates during and after fights and thus represent significant costs of
      signalling. We tested this by analysing the concentrations of lactate and glucose
      in the haemolymph of hermit crabs following agonistic interactions over the
      ownership of the gastropod shells that they inhabit. Attackers and defenders play
      distinct roles of sender and receiver that are fixed for the course of the
      encounter. Attackers perform bouts of 'shell rapping', which vary in vigour
      between attackers and during the course of the encounter, and are a key predictor
      of victory. In contrast to the agonistic behaviour of other species, we can
      quantify the vigour of fighting. We demonstrate, to our knowledge for the first
      time, an association between the vigour of aggressive activity and a proximate
      cost of signalling. We show that the lactate concentration in attackers increases
      with the amount of shell rapping, and that this appears to constrain the vigour
      of subsequent rapping. Furthermore, attackers, but not defenders, give up when
      the concentration of lactate is high. Glucose levels in attackers also increase
      with the amount of rapping they perform, but do not appear to influence their
      decision to give up. Defenders are more likely to lose when they have
      particularly low levels of glucose. We conclude that the two roles use different
      decision rules during these encounters.

PMID- 11522203
TI  - Arbovirus infection increases with group size.
AB  - Buggy Creek (BCR) virus is an arthropod-borne alphavirus that is naturally
      transmitted to its vertebrate host the cliff swallow (Petrochelidon pyrrhonota)
      by an invertebrate vector, namely the cimicid swallow bug (Oeciacus vicarius). We
      examined how the prevalence of the virus varied with the group size of both its
      vector and host. The study was conducted in southwestern Nebraska where cliff
      swallows breed in colonies ranging from one to 3700 nests and the bug populations
      at a site vary directly with the cliff swallow colony size. The percentage of
      cliff swallow nests containing bugs infected with BCR virus increased
      significantly with colony size at a site in the current year and at the site in
      the previous year. This result could not be explained by differences in the bug
      sampling methods, date of sampling, sample size of the bugs, age structure of the
      bugs or the presence of an alternate host, the house sparrow (Passer domesticus).
      Colony sites that were reused by cliff swallows showed a positive autocorrelation
      in the percentage of nests with infected bugs between year t and year t+1, but
      the spatial autocorrelation broke down for year t+2. The increased prevalence of
      BCR virus at larger cliff swallow colonies probably reflects the larger bug
      populations there, which are less likely to decline in size and lead to virus
      extinction. To the authors' knowledge this is the first demonstration of
      arbovirus infection increasing with group size and one of the few known
      predictive ecological relationships between an arbovirus and its vectors/hosts.
      The results have implications for both understanding the fitness consequences of
      coloniality for cliff swallows and understanding the temporal and spatial
      variation in arboviral epidemics.

PMID- 11522205
TI  - Disruptive sexual selection against hybrids contributes to speciation between
      Heliconius cydno and Heliconius melpomene.
AB  - Understanding the fate of hybrids in wild populations is fundamental to
      understanding speciation. Here we provide evidence for disruptive sexual
      selection against hybrids between Heliconius cydno and Heliconius melpomene. The
      two species are sympatric across most of Central and Andean South America, and
      coexist despite a low level of hybridization. No-choice mating experiments show
      strong assortative mating between the species. Hybrids mate readily with one
      another, but both sexes show a reduction in mating success of over 50% with the
      parental species. Mating preference is associated with a shift in the adult
      colour pattern, which is involved in predator defence through Mullerian mimicry,
      but also strongly affects male courtship probability. The hybrids, which lie
      outside the curve of protection afforded by mimetic resemblance to the parental
      species, are also largely outside the curves of parental mating preference.
      Disruptive sexual selection against F(1) hybrids therefore forms an additional
      post-mating barrier to gene flow, blurring the distinction between pre-mating and
      post-mating isolation, and helping to maintain the distinctness of these
      hybridizing species.

PMID- 11522206
TI  - Very large long-term effective population size in the virulent human malaria
      parasite Plasmodium falciparum.
AB  - It has been proposed that the virulent human malaria parasite Plasmodium
      falciparum underwent a recent severe population bottleneck. In order to test this
      hypothesis, we estimated the effective population size of this species from the
      patterns of nucleotide substitution at 23 nuclear protein-coding loci, using a
      variety of methods based on coalescent theory. Both simple methods and
      phylogenetically based maximum-likelihood methods yielded the conclusion that the
      effective population size of this species has been of the order of at least 10(5)
      for the past 300,000-400,000 years.

PMID- 11522207
TI  - Local reinforcement and recombination in classifier systems.
AB  - We investigate classifier systems' reward schemes by way of an example that
      highlights the interaction of local reward schemes and recombination. We contrast
      averaging schemes and maximizing schemes. Our example illustrates a sense in
      which certain recombination operators mesh more gracefully with averaging schemes
      than with maximizing schemes.

PMID- 11522208
TI  - An analysis of two-parent recombinations for real-valued chromosomes in an
      infinite population.
AB  - This paper concerns recombinations which produce offspring from two parents. We
      assume an infinite population and regard recombinations as transformations of
      stochastic variables represented as chromosomes. We then formalize recombinations
      with the probability density functions of stochastic variables represented as the
      parameters and describe the change of the probability density functions of
      chromosomes before and after recombination. Our formalization includes various
      proposed recombinations, such as multi-point, uniform, and linear crossover, as
      well as BLX-alpha. We also derive certain properties of the operators, such as
      diversification and decorrelation.

PMID- 11522209
TI  - Constructive genetic algorithm for clustering problems.
AB  - Genetic algorithms (GAs) have recently been accepted as powerful approaches to
      solving optimization problems. It is also well-accepted that building block
      construction (schemata formation and conservation) has a positive influence on GA
      behavior. Schemata are usually indirectly evaluated through a derived structure.
      We introduce a new approach called the Constructive Genetic Algorithm (CGA),
      which allows for schemata evaluation and the provision of other new features to
      the GA. Problems are modeled as bi-objective optimization problems that consider
      the evaluation of two fitness functions. This double fitness process, called fg
      fitness, evaluates schemata and structures in a common basis. Evolution is
      conducted considering an adaptive rejection threshold that contemplates both
      objectives and attributes a rank to each individual in population. The population
      is dynamic in size and composed of schemata and structures. Recombination
      preserves good schemata, and mutation is applied to structures to get population
      diversification. The CGA is applied to two clustering problems in graphs.
      Representation of schemata and structures use a binary digit alphabet and are
      based on assignment (greedy) heuristics that provide a clearly distinguished
      representation for the problems. The clustering problems studied are the
      classical p-median and the capacitated p-median. Good results are shown for
      problem instances taken from the literature.

PMID- 11522210
TI  - Design of graph-based evolutionary algorithms: a case study for chemical process
      networks.
AB  - This paper describes the adaptation of evolutionary algorithms (EAs) to the
      structural optimization of chemical engineering plants, using rigorous process
      simulation combined with realistic costing procedures to calculate target
      function values. To represent chemical engineering plants, a network
      representation with typed vertices and variable structure will be introduced. For
      this representation, we introduce a technique on how to create problem specific
      search operators and apply them in stochastic optimization procedures. The
      applicability of the approach is demonstrated by a reference example. The design
      of the algorithms will be oriented at the systematic framework of metric-based
      evolutionary algorithms (MBEAs). MBEAs are a special class of evolutionary
      algorithms, fulfilling certain guidelines for the design of search operators,
      whose benefits have been proven in theory and practice. MBEAs rely upon a
      suitable definition of a metric on the search space. The definition of a metric
      for the graph representation will be one of the main issues discussed in this
      paper. Although this article deals with the problem domain of chemical plant
      optimization, the algorithmic design can be easily transferred to similar network
      optimization problems. A useful distance measure for variable dimensionality
      search spaces is suggested.

PMID- 11522211
TI  - Form invariance and implicit parallelism.
AB  - Holland's schema theorem (an inequality) may be viewed as an attempt to
      understand genetic search in terms of a coarse graining of the state space.
      Stephens and Waelbroeck developed that perspective, sharpening the schema theorem
      to an equality. Of particular interest is a "form invariance" of their equations;
      the form is unchanged by the degree of coarse graining. This paper establishes a
      similar form invariance for the more general model of Vose et al. and uses the
      attendant machinery as a springboard for an interpretation and discussion of
      implicit parallelism.

PMID- 11522212
TI  - Adversarial search by evolutionary computation.
AB  - In this paper, we consider the problem of finding good next moves in two-player
      games. Traditional search algorithms, such as minimax and alpha-beta pruning,
      suffer great temporal and spatial expansion when exploring deeply into search
      trees to find better next moves. The evolution of genetic algorithms with the
      ability to find global or near global optima in limited time seems promising, but
      they are inept at finding compound optima, such as the minimax in a game-search
      tree. We thus propose a new genetic algorithm-based approach that can find a good
      next move by reserving the board evaluation values of new offspring in a partial
      game-search tree. Experiments show that solution accuracy and search speed are
      greatly improved by our algorithm.

PMID- 11522213
TI  - The changing incidence of four AIDS-related malignancies in a large urban center.

PMID- 11522214
TI  - Fungemia in HIV-infected patients: a 12-year study in a tertiary care hospital.
AB  - Opportunistic infections caused by fungi are common in human immunodeficiency
      virus (HIV)-infected patients. We focused on severe infections as indicated by
      detectable fungemia. Medical charts available for patients having positive blood
      cultures with fungi at the University of Geneva Hospital were retrospectively
      (1989 to 2000) reviewed. Of 328 patients with fungemia during the study period,
      315 (96%) medical charts were accessible. Of these 315 patients, 37 (12.2%) were
      HIV-positive, and 13 (35.1%) died within 6 months from their episode of fungemia.
      This was a lower mortality rate than for the HIV seronegative patients (45.8%).
      The median and average age of the 34 HIV-positive patients was 37.2 years, and 24
      (64.9%) were males. Cryptococcus neoformans (n = 14) and Candida albicans (n =
      12) were the most frequently identified species, followed by Candida glabrata (n
      = 3), of which 3 were mixed C. albicans + C. glabrata, Histoplasma capsulatum (n
      = 2), and Penicillium marneffei (n = 2). The frequency decreased significantly (p
      < 0.007) from the time period 1993 to 1996 (n = 21) to the period 1997 to 2000 (n
      = 6). Fungemias in HIV-infected patients have declined significantly since 1996.
      This coincides with the introduction of highly active antiretroviral therapy
      (HAART).

PMID- 11522215
TI  - HIV-associated wasting in the HAART era: guidelines for assessment, diagnosis,
      and treatment.
AB  - Wasting (malnutrition) and lipodystrophy are the two major nutritional
      alterations in human immunodeficiency virus (HIV)-infected individuals. Both
      wasting and lipodystrophy may involve a decrease in body fat content, while
      wasting-but not lipodystrophy-also includes the loss of lean body mass.
      Lipodystrophy has made the identification of wasting increasingly more difficult.
      The diagnosis of wasting depends on a definition of the condition that takes into
      account sex and cultural differences, as well as measurements of body cell mass.
      Patient management involves a concurrent, comprehensive approach designed to
      restore lost body cell mass and weight. The authors make recommendations for
      defining, diagnosing, and treating HIV-associated wasting. Specific therapies
      include testosterone replacement, other anabolic steroids, and recombinant human
      growth hormone. Other adjunctive measures, such as progressive resistance
      exercise and cytokine modulation, may also be utilized. Expected outcomes from
      effective treatment include restored body cell mass, improvement in quality of
      life, and reduced rates of hospitalization. Future directions for research should
      address the need for optimal treatment strategies.

PMID- 11522216
TI  - AIDS in South and Southeast Asia. Introduction and greeting. Presented at the
      observance of World AIDS Day, November 30, 2000 at the United Nations.

PMID- 11522217
TI  - Preventing transmission of HIV: a biological and medical perspective.

PMID- 11522218
TI  - HIV/AIDS: perspective on China.

PMID- 11522219
TI  - HIV/AIDS: perspective on India.

PMID- 11522220
TI  - HIV/AIDS: perspective on Thailand.

PMID- 11522221
TI  - HIV/AIDS: international perspective.

PMID- 11522222
TI  - PEP offered in New York.

PMID- 11522223
TI  - Parents want AIDS education.

PMID- 11522226
TI  - Cellular therapy: finishing the job.

PMID- 11522227
TI  - Hans-G. Klingemann, M.D., Ph.D. Interview by Vicki P. Glaser.

PMID- 11522228
TI  - Therapeutic potential of 4-1BB (CD137) as a regulator for effector CD8(+) T
      cells.
AB  - A fundamental problem of antitumor immunity is tumor-induced immunosuppression.
      Tumor cells often down-regulate expression of co-stimulatory molecules, tumor
      antigens, and major histocompatibility complex (MHC) molecules on tumor cells,
      secrete immunosuppressive substance such as transforming growth factor-beta (TGF
      beta) or interleukin-4 (IL-4), and induce apoptosis of effector T cells to escape
      surveillance. A major goal of antitumor or antivirus immunotherapy is to generate
      long-lived protective T cells that enable killing of target cells. In this
      review, we discuss the importance of 4-1BB for development or survival of
      functionally active effector CD8(+) T cells against tumors, virus infection, and
      allogeneic immune responses and for potential therapeutic application.

PMID- 11522229
TI  - The biology of natural killer cells and implications for therapy of human
      disease.
AB  - Natural killer (NK) cells are unique lymphocytes capable of lysing target cells
      without prior immunization. NK cells activated with cytokines, like interleukin-2
      (IL-2), have been used since the 1980s as adoptive immunotherapy against
      metastatic solid tumors, but their effectiveness has been limited. The mechanisms
      by which NK cells recognize their targets are complex, including newly identified
      receptors that recognize class I MHC molecules. Understanding these mechanisms
      may support the use of NK cells as clinical therapy against infectious diseases
      and cancer. We have been interested in the use of NK cells clinically for their
      potential to eradicate minimal residual disease and prevent relapses after
      autologous stem cell transplantation. Several strategies are discussed to
      increase the specificity and efficacy of NK cell therapy. One method is to
      increase the targeting of NK cells by the use of monoclonal antibodies. Another
      approach uses allogeneic NK cells to overcome the inhibitory receptor mechanisms
      that may block target cell lysis by recognition of class I molecules. These and
      other novel strategies may prove to be attractive and effective immunotherapeutic
      tools to manipulate NK cells to fight human disease.

PMID- 11522230
TI  - The graft-versus-tumor potential of allogeneic cell therapy: an update on donor
      leukocyte infusions and nonmyeloablative allogeneic stem cell transplantation.

PMID- 11522232
TI  - Specific T cell therapy in leukemia.

PMID- 11522231
TI  - Controlling culture dynamics for the expansion of hematopoietic stem cells.
AB  - The ex vivo expansion of hematopoietic stem cells (HSCs) is the subject of
      intense commercial and academic interest due to the potential of HSCs to be a
      renewable source of material for cellular therapeutics. Unfortunately, because
      methodologies have not yet been developed to grow clinically relevant numbers of
      HSCs (or their derivatives) consistently, the potential of this technology is
      limited. Manipulation of the in vitro culture microenvironment, primarily through
      cytokine supplementation, has been the predominant approach in studies attempting
      to expand primary human HSC numbers in vitro. While promising results have been
      obtained, it is becoming clear that novel methods must be developed before
      cellular therapies using these stem cells can become routine. Ideally,
      bioprocesses must be designed to target specifically the growth of stem cell
      populations while incorporating positive and negative feedback from potentially
      dynamic mature and maturing cell populations. The product of these culture
      systems should consist of not only HSCs, but also of cells that allow the
      engraftment of HSCs and, ideally, cells responsible for the immediate or
      accelerated functional support of patients. Development of such "designer
      transplants" will require combining optimal culture conditions capable of
      amplifying HSC numbers with novel approaches for finely controlling the number,
      functional capabilities, and characteristics of potentially therapeutic cells in
      these very complex cell culture systems.

PMID- 11522233
TI  - Preparation of autologous leukemia and lymphoma vaccines expressing alpha-gal
      epitopes.
AB  - This study describes a novel method for increasing the immunogenicity of
      autologous tumor vaccines in leukemia and lymphoma patients by exploiting the
      natural anti-Gal antibody for in situ targeting of the vaccinating cells to
      antigen-presenting cells (APCs). Incubation of leukemia or lymphoma cells with
      neuraminidase and recombinant alpha 1,3-galactosyltransferase results in the
      synthesis of many alpha-gal epitopes (Gal alpha 1-3Gal beta 1-4GlcNAc-R) on their
      cell membranes. Vaccination with such processed tumor cells results in the
      binding of the natural anti-Gal immunoglobulin G (IgG) antibody to these epitopes
      and opsonization of these cells for effective phagocytosis by APCs, such as
      dendritic cells and macrophages. These APCs may transport the vaccine to adjacent
      draining lymph nodes for subsequent effective processing and presentation of
      tumor-associated antigens (TAA) peptides to activate TAA-specific helper and
      cytotoxic T cells. Once the TAA-specific cytotoxic T cells are activated, they
      can leave the lymph node, circulate in the body, and seek metastatic cells
      expressing TAA to destroy them. Alternatively, activated helper T cells may
      provide the help required for B cells to produce antibodies to TAA on the
      leukemia or lymphoma cells. Because every patient receives his or her own TAA
      within the vaccinating cells, such vaccines are customized for the patient. These
      autologous tumor vaccines may be used as an adjuvant treatment that complements
      currently used treatment regimens by providing the immune system with an
      additional opportunity to be exposed effectively to autologous TAA.

PMID- 11522234
TI  - Optimal timing for the collection and in vitro expansion of cytotoxic CD56(+)
      lymphocytes from patients undergoing autologous peripheral blood stem cell
      transplantation.
AB  - To identify the optimal time for the collection of CD56(+) cytotoxic lymphocytes
      for adoptive immunotherapy in patients undergoing high-dose chemotherapy (HDCT)
      and peripheral blood stem cell (PBSC) transplantation, 18 breast cancer patients
      receiving either three cycles of epirubicin/paclitaxel (CT x 3) followed by HDCT
      and PBSC transplantation (n = 12) or CTx6 (n = 6) were studied. Blood samples
      were obtained before each CT/HDCT cycle, from PBSC collections, and repeatedly
      after autografting for up to 12 months. The number of CD56(+)3(-) and CD56(+)3(+)
      lymphocytes, their in vitro expandability with interleukin-2, and their
      cytotoxicity against MCF-7 and Daudi cells were analyzed. Six healthy females
      served as controls. CD56(+) cell counts in both treatment groups were subnormal
      but stable during the observation period. The cytotoxicity of the expanded
      CD56(+) cells was normal and unaffected by the treatment. The in vitro CD56(+)
      cell expandability (controls, 100 +/- 31-fold, mean +/- SEM) was normal before
      CT1 and CT2, but reduced in PBSC harvests performed after CT2 and application of
      G-CSF (21 +/- 6-fold; p < 0.01). After PBSC harvesting, the CD56(+) cell
      expandability increased to 185 +/- 74-fold and 170 +/- 69-fold (before CT3 and
      HDCT). This increase was not observed in those patients who did not undergo PBSC
      mobilization. Two weeks after autografting, the CD56(+) cell expandability was
      minimal (6 +/- 1-fold), and recovered to 34 +/- 6-fold. Thus, CT, HDCT and
      autografting do not alter the frequency and inducible cytotoxicity of CD56(+)
      cells in breast cancer patients. However, the proliferative capacity of CD56(+)
      cells obtained from PBSC harvests and after autografting is impaired. Therefore,
      instead of the PBSC graft, maximally expandable CD56(+) cells obtained at least 1
      week after PBSC collection should be considered for adoptive immunotherapy after
      PBSC autografting.

PMID- 11522235
TI  - Chimeric antigen receptors for the retargeting of cytotoxic effector cells.
AB  - T lymphocytes recognize specific antigens through interaction of the T cell
      receptor (TCR) with short peptides presented by major histocompatibility complex
      (MHC) class I or II molecules. For initial activation and clonal expansion, naive
      T cells are dependent on professional antigen-presenting cells (APCs) that
      provide additional co-stimulatory signals. TCR activation in the absence of co
      stimulation can result in unresponsiveness and clonal anergy. To bypass
      immunization, different approaches for the derivation of cytotoxic effector cells
      with grafted recognition specificity have been developed. Chimeric antigen
      receptors have been constructed that consist of binding domains derived from
      natural ligands or antibodies specific for cell-surface antigens, genetically
      fused to effector molecules such as the TCR alpha and beta chains, or components
      of the TCR-associated CD3 complex. Upon antigen binding, such chimeric receptors
      link to endogenous signaling pathways in the effector cell and generate
      activating signals similar to those initiated by the TCR complex. Since the first
      reports on chimeric antigen receptors, this concept has steadily been refined and
      the molecular design of chimeric receptors has been optimized. Aided by advances
      in recombinant antibody technology, chimeric antigen receptors targeted to a wide
      variety of antigens on the surface of cancer cells and of cells infected by human
      immunodeficiency virus (HIV) have been generated. In initial clinical studies,
      infusion of such cells into patients proved to be safe and transient therapeutic
      effects have been observed.

PMID- 11522236
TI  - Cellular immunotherapy of malignancies using the clonal natural killer cell line
      NK-92.
AB  - For years activated natural killer (A-NK) cells have been explored with respect
      to their efficacy in anticancer therapy, but, except for some anectdotal reports,
      no clear clinical benefit has been shown. However, as the understanding about the
      interactions of NK cells and tumor cells advances, the use of A-NK cells might be
      revisited with more sophisticated approaches that pay tribute to mechanisms which
      allow tumor cells to escape immune surveillance. Here the highly cytotoxic NK
      cell line NK-92 seems to be an attractive alternative for use in adoptive
      immunotherapy, because it was shown to exhibit substantial antitumor activity
      against a wide range of malignancies in vitro as well as in xenografted SCID
      mice. NK-92 cells are characterized by an almost complete lack of killer cell
      immunglobulin-like receptors (KIRs) yet conserved ability to perforin and
      granzyme B-mediated cytolytic activity, which make them unique among the few
      established NK and T cell-like cell lines. NK-92 is the only natural killer cell
      line that has entered clinical trials. Here we discuss the current status of
      development of this cell line for adoptive immunotherapy (AIT) of malignancies
      and review our first clinical experience in patients with advanced cancer who
      have received repeated transfusions of irradiated NK-92 in a phase I/II trial.
      Also we discuss issues that address safety aspects of immunotherapy with clonal
      cell lines and describe further manipulations, which hold the potential of
      significantly improving the clinical outcome of AIT with NK-92.

PMID- 11522237
TI  - Ex vivo purging of stem cell autografts using cytotoxic cells.
AB  - Autologous stem cell transplantation (SCT) is the treatment alternative offered
      to patients that cannot benefit from allogeneic transplantation due to lack of
      suitable donor or age limitations. However, the outcome of autologous SCT is
      largely hindered by the high relapse rate. Two major factors can account for
      relapse after autologous SCT: the persistence of residual malignant cells
      resistant to chemo/radiotherapy left either in the body or in the autograft.
      Therefore, the rationale for purging autografts of residual malignant cells comes
      from the limitations of conventional high-dose chemo/radiotherapy in achieving a
      complete eradication of residual tumor cells in the marrow. To date, different
      purging modalities have been exploited. Immunological methods of purging present
      the advantage of being non-cross-reactive with conventional chemotherapy. These
      immunologic methods include depletion using antibody targeting of the malignant
      cells, ex vivo activation/generation of the autologous cytotoxic cells, in
      particular that of natural killer/lymphokine-activated killer (NK/LAK) and
      cytokine-induced killer (CIK) cells, and ex vivo purging of autografts using
      cytotoxic cell lines. The generation of ex vivo-expanded and activated autologous
      cytotoxic cells (CTL or NK) has generated increasing interest for the treatment
      of different malignancies. Unfortunately, the isolation and expansion of these
      cells have proven to be technically difficult. As an alternative, the use of
      cytotoxic cell lines as immune effectors has been proposed. The two available
      human cytotoxic cell lines TALL104 and NK-92 are currently in clinical trials and
      a number of studies have suggested their effectiveness as an immunotherapeutic
      agent including for ex vivo purging of autografts.

PMID- 11522238
TI  - In vitro production of dendritic cells from human blood monocytes for therapeutic
      use.
AB  - Dendritic cells (DC) are professional antigen-presenting cells that are promising
      adjuvants for clinical immunotherapy. Methods to generate in vitro large numbers
      of functional human DC using either peripheral blood monocytes or CD34(+)
      pluripotent hematopoietic progenitor cells have been now developed. For this
      purpose, their in vitro production for further clinical use need to fit good
      manufacturing practice (GMP) conditions. In the present review, we give our
      experience of such a procedure: it includes collection of mononuclear cells by
      apheresis, separation of monocytes by elutriation, and culture of monocytes with
      GM-CSF + IL-13 + human serum (autologous patient's serum or AB serum) or in a
      serum-free medium (AIM V). The characteristics of monocyte-derived DC grown in
      these various conditions varied mainly regarding their phenotype and their
      morphology in confocal microscopy, whereas no significant differences were found
      in their capacity to phagocytize latex particles and to stimulate allogeneic
      (MLR) or autologous lymphocytes (antigen-presentation tests). The DC were also
      cryopreserved in bags (either by putting the bags directly in a -80 degrees C
      mechanical freezer or using a classical liquid nitrogen controlled-rate freezer
      at -1 degrees C/min) in a solution containing 10% dimethyl sulfoxide (Me(2)SO)
      and 2% human albumin in doses of DC available for several infusions. The mean
      recoveries after freezing and thawing were not statistically different (around
      70%). The immunophenotype of DC, as well as the T lymphocyte-stimulating
      capacity, were not modified by the freezing--thawing procedure. The results
      obtained demonstrate that the experimental conditions we set up are easily
      applicable in clinical trials and lead to large numbers of well-defined DC.
      Clinical trials using DC already published will be discussed.

PMID- 11522240
TI  - Stem cells: preparing for the pitfalls that must inevitably precede the promise.

PMID- 11522239
TI  - Differential effects of autologous serum on CD34(+) or monocyte-derived dendritic
      cells.
AB  - Dendritic cells (DC) with potentially important clinical applications have been
      generated from human peripheral blood monocytes and CD34(+) cells in the presence
      of recombinant cytokines granulocyte-macrophage colony-stimulating factor (GM
      CSF) + interleukin-4 (IL-4) and GM-CSF + tumor necrosis factor-alpha (TNF-alpha),
      respectively. Many of the studies generating DC have included fetal calf serum,
      which is not desirable due to the risk of immune reactions and infectious disease
      transmission. Additionally, low DC yields have been reported using serum-free
      media. In this study, we investigate supplementing serum-free media with
      autologous serum and plasma for DC generation from monocytes and CD34(+) cells.
      Our results show that functional DC can be reproducibly obtained in the presence
      of autologous serum using monocytes and CD34(+) cells as the starting
      populations. However, with the addition of autologous serum, a differential
      effect is observed in the phenotypic characterization of these culture-derived
      DC. Monocytes cultured for 7 days in X-VIVO 15 serum-free media in the presence
      of GM-CSF + IL-4 showed down-regulation of CD14 with increased expression of HLA
      DR, mannose receptor, CD80, and CD86, along with highly up-regulated CD1a(+)
      expression. The addition of autologous serum to serum-free media in monocyte
      cultures resulted in a dose-dependent decrease in the CD1a(+) expression
      generating a distinct subset of CD1a(+/-) cells expressing HLA-DR, mannose
      receptor, CD80, and CD86. Upon stimulation with CD40L cells, both monocyte
      derived DC subsets CD1a(+/-) and CD1a(++) were capable of maturation measured by
      CD83 and CD86 up-regulation. Data suggest the differences in the monocyte-derived
      DC in serum-free (CD1a(++)) or autologous serum (CD1a(+/-)) supplemented cultures
      is of a qualitative nature, rather than quantitative. CD1a(+) and CD14(+) cells
      expressing HLA-DR, mannose receptor, CD80, and CD86 were generated in 7 days from
      CD34(+) cells in serum-free media. A quantitative effect was obtained when
      cultures were supplemented with autologous serum, resulting in a significant
      enhancement of CD34-derived DC generated. These results demonstrate generation of
      DC from two different starting populations using serum-free media that can be
      enhanced with the addition of autologous serum. Interestingly, a differential
      effect was observed in the phenotypic characterization of these culture-derived
      DC.

PMID- 11522241
TI  - Episphalosomic syndrome : a MCA syndrome ressembling Fanconi anemia, with
      increased baseline level of chromosome breaks but no hypersensivity to
      clastogens.
AB  - We describe a child with facial dysmorphism (trigonocephaly, epicanthus, upturned
      nose, small ears), thumb hypoplasia, micropenis, jejunal atresia and moderate
      mental retardation with dysphasia. Cytogenetic workup revealed high spontaneous
      level of chromosomal aberrations (without specific pattern and no quadriradial
      figures) and borderline to absent hypersensitivity to mitomycin C, making a
      diagnosis of Fanconi anemia unlikely. The child described here shares
      similarities with a small number of previous reports. We suggest to refer to this
      entity as episphalosomic syndrome. Episphalosomic syndrome shows some clinical
      overlap with Fanconi anemia, but lacks its cytogenetic hallmark. The
      hematological complications of Fanconi anemia have not been reported in this
      entity.

PMID- 11522242
TI  - An unbalanced translocation 46,XX,+der(18)t(18;21)(q12.2;q11.2)mat,-21 associated
      with maternal isodisomy 18pter-->18q12.2.
AB  - We report a patient with a 46,XX,+der(18)t(18;21)(q12.2;q11.2)mat,-21 karyotype,
      in whom the rarely seen adjacent-2 segregation (according to the predicted
      pachytene diagram model) as well as two cross-overs, resulted in maternal
      isodisomy 18pter-->18q12.2.

PMID- 11522243
TI  - An infant with Turner-Down aneuploidy and massive capillary hemangioma of the
      orbit: a case report with review.
AB  - We report on a case of double aneuploidy involving Down and Turner cell lines in
      a female child with a massive capillary hemangioma of the left orbit and mild
      clinical features of Down syndrome. Cytogenetic findings with G-banding revealed
      mosaicism in her peripheral blood, i.e.
      mos45,X[48]/47,XX,+21[28]/46,XX[12/47,XXX[12]. Mosaicism of such nature is rare
      and to our knowledge the present case is the first reported of Turner-Down double
      aneuploidy mosaicism associated with an orbital capillary hemangioma. An
      annotated bibliography of earlier reported cases with documented karyotyping is
      also included.

PMID- 11522244
TI  - Xp22.3; Yq11.2 chromosome translocation and its clinical manifestations.
AB  - We report clinical and molecular investigations in a boy with karyotype
      46,Y,der(X)t(X;Y)(qter-->p22.3::q11.21-->qter) and his mother with karyotype
      46,X,der(X)t(X;Y)(qter-->p22.3::q11.21-->qter). Haplo-insufficiency for the
      Xp22.3-->pter chromosomal region in the boy resulted in postnatal growth
      retardation, developmental delay, partial ichthyosis and facial dysmorphism, but
      normal external genitals. His mother has a normal phenotype with normal stature
      and gonadal function but borderline intelligence. FISH-analysis showed a
      duplication of the Y-heterochromatin probe in the proband and a deletion of the
      Y933D4 probe in his mother. Molecular investigations situated the Xp22.3
      breakpoint between DXS278 and the KAL gene and the Yq11.21 breakpoint between the
      DYS391 and DYS390 in the proband and his mother. X-inactivation study was
      performed by analysis of the polymorphic CAG-repeat in the androgen-receptor gene
      as described showing a normal random (40% versus 60%) inactivation pattern in the
      mother. The manifestations in male and female with loss of the Xp22.3-->pter and
      gain of the Yq11.21-->qter chromosomal region are discussed.

PMID- 11522245
TI  - Condensed chromatin surface and NORs surface enhancement in mitogen-stimulated
      lymphocytes of Down syndrome patients.
AB  - Mitogen-stimulated lymphocytes of 20 Down syndrome (DS) patients with regular
      trisomy 21 contain more condensed chromatin surface (11.28 +/- 2.64 % of the
      total nuclear surface: mean +/- SD) and more nucleolus organiser regions surface
      (13.21 +/- 3.45 %) than that of 12 healthy controls: (8.84 +/- 2.23 and 9.12 +/-
      2.33 %, reciprocally). The source of this peculiarity has been investigated. A
      computer program was designed for the planimetric measurement of the condensed
      chromatin surface (CCs)/ total nuclear surface(TNs) and the nucleolus organiser
      regions surface (NORss) /TNs proportions in interphase nuclei. CCs/TNs and
      NORss/TNs of 100 maximally activated nuclei (MANs) were measured for each patient
      and control case. The difference was found highly significant (P<0.01). Nuclei
      with a diameter of >/= 17 micrometer measured on the slide (in flattened state)
      were considered as maximally activated nuclei (MANs). NORss/TNs enhancement and
      fluorescent in situ hybridisation (FISH) studies in MANs of DS patients indicate
      that this phenomenon is due to the over-expression (or lack of downregulative
      mechanism) of NORs (rDNA) to some extent, including the NOR of the supernumerary
      chromosome 21. No statistical difference was observed between 12 healthy controls
      and 5 Robertsonian translocation type of DS Patients (where the two involved NORs
      are missing) when the two parameters were considered.

PMID- 11522246
TI  - Fetal and placenta chromosome constitution in 237 pregnancy losses.
AB  - The aim of the study was to carry out cytogenetic analyses in pregnancy losses.
      Samples of cartilage and placenta tissue were obtained prospectively from 237
      pregnancy losses of more than 16 weeks of gestation (130 stillbirths, 97 induced
      abortions and 10 early neonatal deaths). Cartilage culture was performed in 222
      samples and placental culture was initiated in 224. The overall culture success
      rate was 83.5%, 72.3% in stillbirths, 97% in induced abortions and 100% in early
      neonatal death. An abnormal karyotype was detected in 52 cases: 6.9% in
      stillbirths, 43.6% in induced abortions and 20% in early neonatal deaths. The
      rate of discrepancy between the prenatal cytogenetic results in amniotic fluid
      and the post-termination karyotype was 3%. The tissue of choice for cytogenetic
      analysis was cartilage in induced abortions and early neonatal death, and
      placenta in stillbirth. The majority of cases had a chromosome abnormality:
      multiple congenital anomalies in 74.6%, and a single major anomaly in 9.7%.

PMID- 11522247
TI  - Dysmorphology and mental retardation: molecular cytogenetic studies in dysmorphic
      mentally retarded patients.
AB  - In an institutionalised population of 471 mentally retarded adult residents (436
      males and 35 females), 18 patients (16 males and 2 females) with dysmorphic
      features were selected to perform FISH studies by using subtelomeric probes to
      discover cryptic terminal deletions or duplications, undetectable with standard
      banding techniques. In the 13 investigated patients, no abnormalities were found
      with a selected battery of subtelomeric probes. The results of cryptic
      chromosomal rearrangement studies are variable but the frequency of positive
      diagnostic findings seems to be lower than previously expected.

PMID- 11522248
TI  - Cell-cycle kinetics of cell lines from patients with chromosomal mosaicism.
AB  - Lymphocyte cultures from five patients with chromosomal mosaicism (two
      47,XY,+21/46,XY, one 47,XX,+21/46,XX, one 45,X/46,XX, and one 47,XXY/46,XY) were
      studied using sister chromatid differential staining technique for cell kinetic
      evaluation. Aneuploid and normal cell lines were compared to identify changes in
      cellular proliferation in vitro that could be related to cellular selective
      advantage and cell-line-proportion changes occurring with age. Comparison of the
      percentage of cells in different cell generations in 48, 72, and 96 h-cultures
      shows no differences between the aneuploid and normal cell lines indicating that
      cell-cycle kinetics is similar in these cells in vitro.

PMID- 11522249
TI  - Prenatal diagnosis of chromosome disorders in Tunisian population.
AB  - Cytogenetic prenatal diagnosis (PND) is under national health program in most
      developed countries, while it concerns a small part of population at risk in
      developing countries. Finance is common reason of absence of PND development, but
      socio-cultural believes play an important role in Arab Muslim countries. In this
      paper we report results of 3110 fetal karyotypes carried out in a Tunisian
      population, by cultured amniocytes analysis. It is the largest report in a Muslim
      Arab country in our Knowledge. Abnormal karyotypes rate was 4.18% classified in
      two groups: bad prognosis (3.05%) and good prognosis (1.13%). Common
      amniocentesis indication was maternal age. The highest predictive value was
      observed in balanced karyotype and fetal ultrasound findings indications.
      Maternal serum markers were not commonly used for trisomy 21 screening. Pregnancy
      termination that is permitted by legal and religious authorities was accepted by
      94,74% parents. Information about PND outcomes was given by genetic counselling
      prior to fetal sampling, pregnancy interruption was discussed with parents at
      cytogenetic result announcement. The authors conclude that in order to prevent
      mental and physical handicap related to cytogenetic disorders we have to promote
      PND by education for population, genetic counselling and fetal ultrasound
      screening; all three methods available in Tunisia.

PMID- 11522250
TI  - Improved characterization of FSHD mutations.
AB  - Facioscapulohumeral muscular dystrophy (FSHD) is caused by the shortest alleles
      of the 3.3kb-tandem repeat array D4Z4 at 4q35. Molecular diagnosis of FSHD
      depends upon the separation of unusually large alleles by pulse-field
      electrophoresis after EcoRI and EcoRI/BlnI digestion. The exact number of alleles
      could not however be directly inferred from the size of DNA fragments owing to
      polymorphisms in the telomeric region of the locus. Knowing the exact repeat
      number of disease causing alleles may benefit genetic counselling, help to
      understand the mechanism of this singular disease and the population dynamics of
      subtelomeric sequences variations. We present here a partial digestion mapping
      method giving the exact number of repeats for disease causing alleles, and we
      suggest that most inaccuracies induced by common polymorphisms could be reduced
      by using EcoRV in place of EcoRI. After studying more than 300 DNA samples with
      both the standard method and this new method, we show that alleles size can be
      evaluated with a precision of less than one half repeat, and that the variations
      in length of the truncated repeat in the telomeric region of the D4Z4 locus can
      be evaluated. The results suggest that at least one intact chromosome 4 type
      repeat at 4q35 is needed to cause FSHD.

PMID- 11522251
TI  - Analysis of suppressor mutation reveals long distance interactions in the bc(1)
      complex of Saccharomyces cerevisiae.
AB  - Four totally conserved glycines are involved in the packing of the two cytochrome
      b hemes, b(L) and b(H), of the bc(1) complex. The conserved glycine 131 is
      involved in the packing of heme b(L) and is separated by only 3 A from this heme
      in the bc(1) complex structure. The cytochrome b respiratory deficient mutant
      G131S is affected in the assembly of the bc(1) complex. An intragenic suppressor
      mutation was obtained at position 260, in the ef loop, where a glycine was
      replaced by an alanine. This respiratory competent revertant exhibited a low
      bc(1) complex activity and was affected in the electron transfer at the Q(P)
      site. The k(min) for the substrate DBH(2) was diminished by an order of magnitude
      and EPR spectra showed a partially empty Q(P) site. However, the binding of the
      Q(P) site inhibitors stigmatellin and myxothiazol remained unchanged in the
      suppressor strain. Optical spectroscopy revealed that heme b(L) is red shifted by
      0.8 nm and that the E(m) of heme b(L) was slightly increased (+20 mV) in the
      revertant strain as compared to wild type strain values. Addition of a methyl
      group at position 260 is thus sufficient to allow the assembly of the bc(1)
      complex and the insertion of heme b(L) despite the presence of the serine at
      position 131. Surprisingly, reversion at position 260 was located 13 A away from
      the original mutation and revealed a long distance interaction in the yeast bc(1)
      complex.

PMID- 11522252
TI  - Identification of functional regions of Cbp3p, an enzyme-specific chaperone
      required for the assembly of ubiquinol-cytochrome c reductase in yeast
      mitochondria.
AB  - The Cbp3 protein of Saccharomyces cerevisiae is an enzyme-specific chaperone
      required for the assembly of ubiquinol-cytochrome c reductase of the
      mitochondrial respiratory chain. To gain preliminary insight into the role of
      Cbp3p during assembly, 29 independently isolated mutants were examined to define
      functional regions of the protein. Mutants were analyzed with respect to
      respiratory growth, ubiquinol-cytochrome c reductase assembly, and steady state
      amounts of enzyme subunits and Cbp3p. Three regions essential for Cbp3p activity
      were identified: regions 1 and 3 were required for Cbp3p function, while region 2
      was necessary for protein stability. Mutation of Glu134 in region 1 (Cys124
      through Ala140) impaired the ability of the Rieske FeS protein to assemble with
      the enzyme complex. Mutations targeted to region 3 (Gly223 through Asp229)
      primarily affected the 14 kDa subunit and cytochrome c(1) assembly. Gly223 was
      found especially sensitive to mutation and the introduction of charged residues
      at this site compromised Cbp3p functional activity. Region 2 (Leu167 through
      Pro175) overlapped the single hydrophobic domain of Cbp3p. Mutations within this
      area altered the association of Cbp3p with the mitochondrial membrane resulting
      in enhanced protein turnover. The role of the amino-terminus in Cbp3p activity
      was investigated using cbp3 deletion strains Delta12-23, Delta24-54, Delta56-96
      and Delta12-96. All mutants were respiratory competent, indicating that residues
      12-96 were not essential for Cbp3p function, stability or mitochondrial import.
      Analysis of carboxy-terminal deletion mutants demonstrated that the final 44
      residues were not necessary for Cbp3p function; however, alterations in the
      secondary structure of the extreme carboxy-terminal 17 residues affected assembly
      protein activity.

PMID- 11522253
TI  - Photosystem II of peas: effects of added divalent cations of Mn, Fe, Mg, and Ca
      on two kinetic components of P(+)(680) reduction in Mn-depleted core particles.
AB  - The catalytic Mn cluster of the photosynthetic oxygen-evolving system is oxidized
      via a tyrosine, Y(Z), by a photooxidized chlorophyll a moiety, P(+)(680). The
      rapid reduction of P(+)(680) by Y(Z) in nanoseconds requires the intactness of an
      acid/base cluster around Y(Z) with an apparent functional pK of <5. The removal
      of Mn (together with bound Ca) shifts the pK of the acid/base cluster from the
      acid into the neutral pH range. At alkaline pH the electron transfer (ET) from
      Y(Z) to P(+)(680) is still rapid (<1 micros), whereas at acid pH the ET is much
      slower (10-100 micros) and steered by proton release. In the intermediate pH
      domain one observes a mix of these kinetic components (see R. Ahlbrink, M.
      Haumann, D. Cherepanov, O. Bogershausen, A. Mulkidjanian, W. Junge, Biochemistry
      37 (1998)). The overall kinetics of P(680)(+) reduction by Y(Z) in Mn-depleted
      photosystem II (PS II) has been previously shown to be slowed down by divalent
      cations (added at >10 microM), namely: Mn(2+), Co(2+), Ni(2+), Cu(2+), Zn(2+)
      (C.W. Hoganson, P.A. Casey, O. Hansson, Biochim. Biophys. Acta 1057 (1991)).
      Using Mn-depleted PS II core particles from pea as starting material, we re
      investigated this phenomenon at nanosecond resolution, aiming at the effect of
      divalent cations on the particular kinetic components of P(+)(680) reduction. To
      our surprise we found only the slower, proton steered component retarded by some
      added cations (namely Co(2+)/Zn(2+)>Fe(2+)>Mn(2+)). Neither the fast component
      nor the apparent pK of the acid/base cluster around Y(Z) was affected.
      Apparently, the divalent cations acted (electrostatically) on the proton release
      channel that connects the oxygen-evolving complex with the bulk water, but not on
      the ET between Y(Z) and P(+)(680), proper. Contrastingly, Ca(2+) and Mg(2+), when
      added at >5 mM, accelerated the slow component of P(+)(680) reduction by Y(Z) and
      shifted the apparent pK of Y(Z) from 7.4 to 6.6 and 6.7, respectively. It was
      evident that the binding site(s) for added Ca(2+) and Mg(2+) were close to Y(Z)
      proper. The data obtained are discussed in relation to the nature of the metal
      binding sites in photosystem II.

PMID- 11522254
TI  - Quinolones and their N-oxides as inhibitors of photosystem II and the cytochrome
      b(6)/f-complex.
AB  - 4(1H)-quinolones (2-alkyl- (1), 2-alkyl-3-methyl- (2), 2-methyl-3-alkyl- (3), 1
      hydroxy-2-methyl-3-alkyl- (4) and 1-hydroxy-2-alkyl- (5)) with n-alkyl side
      chains varying from C(5) to C(17) have been synthesized and tested for biological
      activity in photosystem II and the cytochrome b(6)/f-complex. In photosystem II,
      quinolones 1 and 2 showed only moderate activity, whereas 3<5<4 (increasing
      activity) were potent inhibitors. Displacement experiments with [(14)C]atrazine
      indicated that the quinolones share an identical binding site with other
      photosystem II commercial herbicides. In the cytochrome b(6)/f-complex, only 3<4
      showed enhanced activity. Maximal inhibitory potency was achieved at a carbon
      chain length of 12-14 A. Further increase of the chain length decreased activity.
      In a quantitative structure-activity relationship inhibitory activity in
      photosystem II and the cytochrome b(6)/f-complex could be correlated to the
      physicochemical parameters lipophilicity pi and/or to STERIMOL L.

PMID- 11522255
TI  - Chlororespiration and the process of carotenoid biosynthesis.
AB  - The plastoquinone pool during dark adaptation is reduced by endogenous reductants
      and oxidized at the expense of molecular oxygen. We report here on the redox
      state of plastoquinone in darkness, using as an indicator the chlorophyll
      fluorescence kinetics of whole cells of a Chlamydomonas reinhardtii mutant strain
      lacking the cytochrome b(6)f complex. When algae were equilibrated with a mixture
      of air and argon at 1.45% air, plastoquinol oxidation was inhibited whereas
      mitochondrial respiration was not. Consequently, mitochondrial oxidases cannot be
      responsible for the oxygen consumption linked to plastoquinol oxidation.
      Plastoquinol oxidation in darkness turned out to be sensitive to n-propyl gallate
      (PG) and insensitive to salicylhydroxamic acid (SHAM), whereas mitochondrial
      respiration was sensitive to SHAM and PG. Thus, both PG treatment and partial
      anaerobiosis allow to draw a distinction between an inhibition of plastoquinol
      oxidation and an inhibition of mitochondrial respiration, indicating the presence
      of a plastoquinol:oxygen oxidoreductase. The possible identification of this
      oxidase with an oxidase involved in carotenoid biosynthesis is discussed in view
      of various experimental data.

PMID- 11522256
TI  - Genetic predisposition and the development of posttraumatic stress disorder in an
      animal model.
AB  - BACKGROUND: Exposure to extremely stressful events can lead to Posttraumatic
      stress disorder (PTSD). Due to the complexity of PTSD, animal models have been
      designed and advanced to address the role of psychosocial stressors in the
      etiology; however, the apparent role of genetics in susceptibility to PTSD-like
      behaviors in animals remains unexplored. METHODS: An animal model of congenital
      learned helpless (cLH) behavior has been used to study the effects of genetic
      disposition as a risk factor for the development of PTSD-like behaviors. Animals
      were monitored for changes in pain tolerance, spatial memory and hypothalamic
      pituitary-adrenal functioning after re-exposure to intermittent stress in the
      presence and absence of situational cues. RESULTS: Exposure to stress resulted in
      an increase in pain tolerance in the cLH animals. In the spatial memory test 80%
      of the cLH animals manifested a decrease in performance after exposure to stress.
      These animals also had a blunted poststress corticosterone response. CONCLUSIONS:
      The genetic learned helpless animal model exhibited physiologic symptoms of
      analgesia, cognitive deficits and hyporesponsivity of the hypothalamic-pituitary
      adrenal axis similar to those observed in human subjects with PTSD. It is
      proposed that the cLH model may be a valuable tool for exploring the role of
      genetic predisposition in the etiology of PTSD.

PMID- 11522257
TI  - Glucocorticoid feedback sensitivity and adrenocortical responsiveness in
      posttraumatic stress disorder.
AB  - BACKGROUND: Decreased basal cortisol levels have been reported in individuals
      with posttraumatic stress disorder (PTSD). There is evidence for enhanced
      negative feedback sensitivity of the hypothalamic-pituitary-adrenal (HPA) axis in
      PTSD, which could account for this, but other possible mechanisms have not been
      ruled out. We examined the HPA axis employing a metyrapone-cortisol infusion
      protocol designed to study negative feedback sensitivity. METHODS: Vietnam combat
      trauma-exposed subjects met DSM-IV criteria for PTSD. Exclusion criteria included
      substance abuse and most medications. Endogenous feedback inhibition was removed
      by blocking cortisol synthesis with oral metyrapone and reintroduced by
      intravenous infusion of cortisol. In a placebo condition, subjects received oral
      placebo and normal saline infusion. Serial blood samples drawn over 4 hours were
      assayed for adrenocorticotrophic hormone (ACTH), cortisol, and 11-deoxycortisol.
      Selected samples were assayed for cortisol binding globulin (CBG) and
      dehydroepiandrosterone (DHEA). RESULTS: Basal plasma cortisol was significantly
      decreased in PTSD subjects (n = 13) compared with control subjects (n = 16). No
      significant difference in the ACTH response to cortisol infusion following
      metyrapone was observed; however 11-deoxycortisol was significantly decreased in
      PTSD subjects. In addition, CBG was significantly increased in PTSD subjects, and
      DHEA was significantly decreased in both PTSD and combat-exposed control
      subjects. CONCLUSIONS: These observations suggest decreased adrenocortical
      responsiveness may be an additional or alternative mechanism accounting for low
      cortisol in PTSD.

PMID- 11522258
TI  - Regional cerebral blood flow correlated with flashback intensity in patients with
      posttraumatic stress disorder.
AB  - BACKGROUND: Nuclear imaging studies have examined cerebral blood flow (rCBF) in
      subjects with posttraumatic stress disorder (PTSD) using symptom evocation
      paradigms. To date, no such studies have investigated rCBF as related to
      subjects' reports of flashback intensity. METHODS: Subjects with varying
      traumatic histories and longstanding PTSD were studied using [15O]-H2O positron
      emission tomography with an auditory script of their traumatic event. Eight
      subjects had three resting scans followed by their script and additional scans.
      Heart rate responses as well as the presence of flashbacks and their intensity
      were recorded. rCBF was correlated with flashback intensity in each subject's
      scan. Combined analysis of all subjects' data yielded common regions related to
      the flashback experience. RESULTS: rCBF correlated directly with flashback
      intensity in the brainstem, lingula, bilateral insula, right putamen and left
      hippocampal and perihippocampal, somatosensory and cerebellar regions. Inverse
      correlations with rCBF were found in bilateral dorsolateral prefrontal, right
      fusiform and right medial temporal cortices. CONCLUSIONS: This study correlated
      flashback intensity and rCBF in a group of patients with chronic PTSD suggesting
      involvement of brainstem, and areas associated with motor control, complex
      visual/spatial cues and memory.

PMID- 11522259
TI  - Abnormal salivary cortisol levels in social phobic patients in response to acute
      psychological but not physical stress.
AB  - BACKGROUND: Little is known about the hypothalamic-pituitary-adrenal axis
      response to acute stressful behavioral challenges in patients with social phobia.
      METHODS: Eighteen patients with social phobia and 17 normal volunteers
      participated in two behavioral stressors: a speech task and physical exercise.
      RESULTS: Normal volunteers (n = 14) demonstrated a significant 50% increase in
      salivary cortisol levels to the speech task. Three nonresponding normal
      volunteers demonstrated a 17% decrease. In contrast, patients with social phobia
      demonstrated dichotomous changes. Seven social phobia patients demonstrated a
      significantly higher 90% increase in salivary cortisol to the speech task,
      whereas the remaining patients (n = 11) were nonresponders demonstrating a 32%
      decrease in cortisol. Both patient groups were significantly more anxious than
      the normal volunteers. In contrast to the response to a speech task, social
      phobics showed a cortisol response to physical exercise of similar magnitude as
      normal volunteers. CONCLUSIONS: The results indicated dichotomies in magnitude
      and in distribution of the cortisol response to a speech task between social
      phobia patients and normal volunteers. Social phobia patients responded
      differently than normal volunteers to a stressor associated with social
      evaluation but not to physical exercise. These results suggest adaptation of
      distinct biological processes specific to different stressful conditions in
      social phobia.

PMID- 11522260
TI  - Increased hippocampal BDNF immunoreactivity in subjects treated with
      antidepressant medication.
AB  - BACKGROUND: The cAMP signaling pathway, and its downstream neurotrophic factor
      BDNF, are major targets of antidepressant medications. Abnormalities in this
      pathway have previously been reported in postmortem brain of subjects with mood
      disorders. This study was designed to test whether the diagnosis of a mood
      disorder, or treatment with an antidepressant or mood stabilizer was associated
      with changes in hippocampal BDNF in postmortem brain. METHODS: Frozen postmortem
      anterior hippocampus sections were obtained from the Stanley Foundation
      Neuropathology Consortium. Tissue from subjects with major depression, bipolar
      disorder, schizophrenia and nonpsychiatric control subjects were stained for BDNF
      using immunohistochemistry. RESULTS: Increased BDNF expression was found in
      dentate gyrus, hilus and supragranular regions in subjects treated with
      antidepressant medications at the time of death, compared with antidepressant
      untreated subjects. Furthermore, there was a trend toward increased BDNF
      expression in hilar and supragranular regions in depressed subjects treated with
      antidepressants, compared with the subjects not on these medications at the time
      of death. CONCLUSIONS: These findings are consistent with recent studies
      measuring CREB levels in this same subject sample, and support current animal and
      cellular models of antidepressant function.

PMID- 11522261
TI  - MRI correlates of suicide attempt history in unipolar depression.
AB  - BACKGROUND: Suicide represents a major health problem in the United States, and
      prediction of suicide attempts is difficult. No structural neuroimaging studies
      have been done to specifically examine findings in patients who have attempted
      suicide. The objective of this study was to compare MRI findings in unipolar
      patients with and without a history of a suicide attempt. METHODS: In this post
      hoc analysis, 20 unipolar subjects with a history of a suicide attempt were
      matched by age and gender to unipolar subjects without a history of an attempt.
      Subjects were also matched on parameters such as cardiovascular history,
      electroconvulsive treatment history, and history of psychosis. Subjects with a
      history of any neurologic condition were excluded. There were no significant
      differences in age of onset of depression, number of episodes of depression, and
      Hamilton Depression scores between the two groups. T2-weighted magnetic resonance
      imaging (MRI) scans were rated using the Coffey and Boyko rating scales. RESULTS:
      Unipolar patients with a history of a suicide attempt demonstrated significantly
      more subcortical gray matter hyperintensities compared with patients without such
      a history. CONCLUSIONS: Patients with abnormal MRI findings may be at higher risk
      for mood disorders and suicide attempts because of disruption of critical
      neuroanatomic pathways. Gray matter hyperintensities in the basal ganglia may be
      especially associated with risk for suicide attempts.

PMID- 11522262
TI  - Decreased pituitary volume in patients with bipolar disorder.
AB  - BACKGROUND: Neuroendocrinologic investigations in bipolar disorder have suggested
      abnormalities in pituitary function. However, few imaging studies have evaluated
      possible anatomical differences in this brain structure in mood disorder
      patients. Our aim was to examine potential abnormalities in pituitary volume in
      patients with bipolar and in a comparison group of patients with unipolar
      disorder. METHODS: We measured the volumes of the pituitary gland in 23 patients
      with bipolar disorder (mean +/- s.d. = 34.3 +/- 9.9 years) and 13 patients with
      unipolar disorder (41.2 +/- 9.6 years), and 34 healthy control subjects (36.6 +/-
      9.6 years) using 1.5 mm thick T1-weighted coronal 1.5 T MRI images. All
      measurements were done blindly by a trained rater. RESULTS: Patients with bipolar
      disorder had significantly smaller pituitary volumes than healthy control
      subjects (mean volume +/- s.d. = 0.55 +/- 0.15 ml and 0.68 +/- 0.20 ml,
      respectively; ANCOVA, F = 8.66, p = 0.005), and than patients with unipolar
      disorder (0.70 +/- 0.12 ml, F = 5.98, p = 0.02). No differences were found
      between patients with unipolar disorder and healthy control subjects (F = 0.01, p
      = 0.91). CONCLUSIONS: To our knowledge, this is the first study that reports
      smaller pituitary volumes in bipolar disorder. Our findings suggest that
      detectable abnormalities in pituitary size are present in patients with bipolar
      disorder, which may reflect a dysfunctional HPA axis.

PMID- 11522263
TI  - Thalamic activation during an attention-to-prepulse startle modification
      paradigm: a functional MRI study.
AB  - BACKGROUND: Prepulse inhibition (PPI) of the startle reflex reflects early stages
      of information processing and is modulated by selective attention. Animal models
      indicate medial frontal-thalamic circuitry is important in PPI modulation. We
      report data from the first functional magnetic resonance imaging (fMRI) study
      examining whether attending to or ignoring a prepulse differentially activates
      brain areas within this circuitry. METHODS: Ten healthy subjects received
      structural and functional MRI. During fMRI acquisition, subjects heard intermixed
      attended and ignored tones serving as prepulses to the startle stimulus. Regions
      of interest were traced on structural MRI and coregistered to fMRI images.
      RESULTS: Greater amplitude fMRI blood-oxygen-level-dependent response to attended
      than ignored PPI conditions occurred in the right thalamus, and bilaterally in
      the anterior and mediodorsal thalamic nuclei, whereas the startle-alone condition
      showed deactivation. In transitional medial cortex (Brodmann Area 32), which is
      involved in affective processing of noxious stimuli, the startle-alone condition
      elicited the greatest response, the attended-PPI condition showed the smallest
      response, and the ignored-PPI condition was intermediate. CONCLUSIONS: These
      findings extend animal models to humans by indicating thalamic involvement in the
      modulation of PPI. Further fMRI investigations may elucidate other key structures
      in the circuitry underlying normal and disordered modulation of PPI.

PMID- 11522264
TI  - Evidence of abnormal amygdala functioning in borderline personality disorder: a
      functional MRI study.
AB  - BACKGROUND: Intense and rapidly changing mood states are a major feature of
      borderline personality disorder (BPD); however, there have only been a few
      studies investigating affective processing in BPD, and in particular no
      neurofunctional correlates of abnormal emotional processing have been identified
      so far. METHODS: Six female BPD patients without additional major psychiatric
      disorder and six age-matched female control subjects underwent functional
      magnetic resonance imaging (fMRI) to measure regional cerebral hemodynamic
      changes following brain activity when viewing 12 standardized emotionally
      aversive slides compared to 12 neutral slides, which were presented in random
      order. RESULTS: Our main finding was that BPD subjects but not control subjects
      were characterized by an elevated blood oxygenation level dependent fMRI signal
      in the amygdala on both sides. In addition, activation of the medial and
      inferolateral prefrontal cortex was seen in BPD patients. Both groups showed
      activation in the temporo-occipital cortex including the fusiform gyrus in BPD
      subjects but not in control subjects. CONCLUSIONS: Enhanced amygdala activation
      in BPD is suggested to reflect the intense and slowly subsiding emotions commonly
      observed in response to even low-level stressors. Borderline subjects' perceptual
      cortex may be modulated through the amygdala leading to increased attention to
      emotionally relevant environmental stimuli.

PMID- 11522265
TI  - Cerebral blood flow velocity in untreated panic disorder patients: a transcranial
      Doppler ultrasonography study.
AB  - BACKGROUND: The aim of this study was to compare resting cerebral blood flow
      velocity values of unmedicated patients in the acute phase of panic disorder with
      resting values of healthy control subjects. METHODS: Nineteen unmedicated panic
      disorder patients were assessed for degree of anxiety using the Hamilton Anxiety
      Scale. The patients and 20 healthy age-matched control subjects were then
      insonated at rest using transcranial Doppler ultrasonography (TCD). For TCD, the
      anterior, the middle, and the posterior cerebral arteries were insonated
      bilaterally in all patients. RESULTS: Compared with healthy age-matched control
      subjects, acute unmedicated panic disorder patients showed a significant increase
      in cerebral blood flow velocity, bilaterally in the middle and the anterior
      cerebral artery, and unilaterally in the left posterior cerebral artery. Cerebral
      blood flow velocity in the right middle cerebral artery correlated positively to
      the item "Fear" on the Hamilton Anxiety Scale, whereas pulsatility index in the
      posterior cerebral artery bilaterally and in the left middle cerebral artery
      correlated negatively to the item "Mood." CONCLUSIONS: Transcranial Doppler
      ultrasonography agrees well with validated psychometric methods. If follow-up
      studies confirm our findings, TCD could allow an objective assessment of the
      mental state of panic disorder patients and reliably discriminate panic disorder
      patients from normal control subjects.

PMID- 11522266
TI  - A pilot longitudinal study of hippocampal volumes in pediatric maltreatment
      related posttraumatic stress disorder.
AB  - BACKGROUND: Adult posttraumatic stress disorder (PTSD) is associated with
      decreased hippocampal volumes; however, decreased hippocampal volumes were not
      seen in pediatric maltreatment-related PTSD. We examined hippocampal volumes
      longitudinally to determine if a history of childhood traumatic stress alters
      hippocampal growth during puberty. METHODS: Magnetic resonance imaging was used
      to measure temporal lobes, amygdala, and hippocampal volumes in nine prepubertal
      maltreated subjects with pediatric maltreatment-related PTSD and nine
      sociodemographically matched healthy nonmaltreated yoked control subjects at
      baseline and after at least 2 years follow-up (during the later stages of
      pubertal development) using identical equipment and measurement methodology.
      RESULTS: Temporal lobe, amygdala and hippocampal volumes did not differ between
      groups at baseline, follow-up, or across time. CONCLUSIONS: Whereas these data
      are from a small sample, the results do not support hippocampal changes in
      pediatric maltreatment-related PTSD.

PMID- 11522269
TI  - Biochemical markers in breast cancer: which ones are clinically useful?
AB  - Breast cancer is the most common neoplasm affecting women in the Western world
      with approximately 1 in 11 developing the malignancy and 1 in 30 dying from the
      disease. For optimum management of these patients, assay of certain biochemical
      markers is necessary. Clinically, the most useful markers in breast cancer are
      the estrogen and progesterone receptors that are used to predict response to
      hormone therapy. Both American and European Expert Panels have recommended
      routine determination of these steroid hormone receptors in all patients with
      breast cancer. For surveillance of patients with diagnosed breast cancer, both CA
      15-3 and BR 27.29 can be used. Serial determinations of these markers have the
      potential to preclinically detect recurrent disease and monitor the treatment of
      advanced disease. However, the benefit of this monitoring on patient outcome or
      quality of life is not clear. New or potentially new markers for breast cancer
      include BRCA1 and BRCA2 for selecting patients at high risk of developing breast
      cancer, urokinase plasminogen activator and PA1-1 for assessing prognosis and HER
      2 for predicting response to the therapeutic antibody, Herceptin.

PMID- 11522270
TI  - Tumor markers in the laboratory: closing the guideline-practice gap.
AB  - Increasing interest in the use of tumor markers in the clinical management of
      cancer patients has encouraged development of guidelines by local, national and
      international groups. Such guidelines generally include recommendations about
      which markers are likely to be most helpful in given circumstances. Particular
      requirements and pitfalls in the preanalytical, analytical and postanalytical
      phases are highlighted. Establishing whether such guidelines are followed in
      routine practice is difficult, but some indication can be obtained through
      carefully designed local and national audit projects. Surveys through external
      quality assessment (proficiency testing) schemes provide a unique means of
      assessing practice and confirming trends. Such surveys suggest that although
      increasing numbers of laboratories in the United Kingdom now measure tumor
      markers, the quality of the service provided over the last ten years has been
      maintained or improved. While much has already been accomplished, further
      narrowing of the gap between theory and practice remains a challenge.

PMID- 11522271
TI  - Analytical evaluation of the Bio-Rad variant II automated HbA(1C) analyzer.
AB  - OBJECTIVES: To evaluate the analytical performance of the Bio-Rad Variant II
      HbA(1C) analyzer (a completely automated system for the quantification of
      glycohemoglobin [HbA(1C)] in blood). DESIGN AND METHODS: The analytical
      parameters of precision, linearity and analytical range were assessed and HbA(1C)
      results from the Variant II were compared to HbA(1C) results from the Bio-Rad
      Variant (a method certified by the National Glycohemoglobin Standardization
      Program). The effect of a variety of hemoglobin variants on HbA(1C) obtained on
      the system was investigated. RESULTS: Total imprecision was less than 5% and the
      results compared well with those from an established method. The method has a
      wide analytical range with no carryover between specimens. CONCLUSION: The
      HbA(1C) method on the Variant II gives acceptable analytical performance.

PMID- 11522272
TI  - Serum thyroxine binding capacity-dependent bias in five free thyroxine
      immunoassays: assessment with serum dilution experiments and impact on diagnostic
      performance.
AB  - OBJECTIVES: To assess the presence and magnitude of a serum thyroxine binding
      capacity (sBC)-dependent bias in five free thyroxine (FT(4)) immunoassays,
      compared with equilibrium dialysis (ED). The exhibited bias is confronted with
      clinical results from previous studies to evaluate its impact on FT(4)
      determination in sera with various sBC. DESIGN AND METHODS: The sera of three
      pregnant women and three non thyroidal ill (NTI) patients were serially diluted
      in an inert buffer to progressively decrease the sBC. FT(4) values were measured
      in diluted and undiluted samples with the six assays. RESULTS: As a function of
      increasing dilution performed on pregnancy sera, except for ED and Vitros ECi
      FT(4,) the other four FT(4) assay results decreased to different degrees, in the
      following order: two-step GammaCoat RIA< Elecsys< ADVIA:Centaur< Amerlex-MAB RIA.
      In sera from NTI patients, the decrease was more marked and found at high
      dilution with the Vitros ECi assay. Data from previous studies showed that FT(4)
      measured with biased assays were decreased only in samples from very severely NTI
      patients with low sBC and that FT(4) results in pregnancy sera with high sBC were
      not significantly biased. CONCLUSIONS: The dilution test is a sensitive alarm to
      assess sBC-dependent bias in FT(4) assays. For all FT4 assays and particularly
      when a bias is observed, documentation should be sought on the diagnostic
      performance of the assay and supported by a detailed clinical study including
      samples with low sBC. Physicians should still be educated about the limitations
      of FT(4) assays.

PMID- 11522273
TI  - Is there a relationship between plasma phenylalanine and cholesterol in
      phenylketonuric patients under dietary treatment?
AB  - OBJECTIVES: To study the lipid profile in a group of treated phenylketonuric
      patients (PKU; n = 61) compared with a group of inborn error of intermediary
      metabolism patients (IEM; n = 22), a group of hyperphenylalaninemic children
      (HPA; n = 37), and a control group without dietary restriction (n = 41). DESIGN
      AND METHODS: Phenylalanine was analyzed by ion exchange chromatography and
      triglycerides, cholesterol and HDL were determined by standard procedures with
      the Cobas Integra analyzer. RESULTS: Serum total cholesterol concentrations were
      significantly lower in PKU patients compared with IEM patients (whose cholesterol
      daily intake was similar to those of PKU patients), HPA children and the control
      group. A negative correlation was observed between cholesterol and phenylalanine
      concentrations in the PKU patients. CONCLUSIONS: Our findings support the
      hypothesis of a relationship between high plasma phenylalanine levels and an
      inhibition of cholesterogenesis, although the low cholesterol intake of the
      special diets may also decrease serum cholesterol values.

PMID- 11522274
TI  - Simultaneous PCR detection of beta - thalassemia and alpha - thalassemia 1 (SEA
      type) in prenatal diagnosis of complex thalassemia syndrome.
AB  - OBJECTIVE: To establish a rapid PCR method for simultaneous detection of beta
      thalassemia and alpha-thalassemia 1 genes for diagnosis of complex alphabeta
      thalassemia syndrome. DESIGN AND METHODS: Using multiplex allele specific PCR
      approach, we evaluated a simultaneous detection of the SEA type alpha-thalassemia
      1 and the common Southeast Asian beta-thalassemia and hemoglobin E genes. The
      system was tested on known cases of double heterozygote for alpha- and beta
      thalassemias and in a prenatal diagnosis of complex alphabeta-thalassemia
      syndrome. RESULTS: Co-inheritance of alpha-thalassemia 1 (SEA type) with each of
      the common beta-thalassemia genes in Southeast Asian and with hemoglobin E could
      be identified in a single PCR reaction. A successful application of this
      simultaneous detection system in prenatal diagnosis of a complex thalassemia
      syndrome caused by an EFBart's disease was demonstrated in a Thai family.
      CONCLUSION: We have shown that correct diagnosis of double heterozygosity for
      alpha-thalassemia 1 and beta-thalassemia or hemoglobin E could be obtained using
      a simultaneous multiplex PCR. These rapid PCR assays would facilitate
      characterization and prenatal diagnosis of complex thalassemia syndromes in the
      regions where both alpha- and beta-thalassemias and hemoglobin E are common.

PMID- 11522275
TI  - Lecithin:cholesterol acyl transferase G30S: association with atherosclerosis,
      hypoalphalipoproteinemia and reduced in vivo enzyme activity.
AB  - OBJECTIVES: A 69 yr old male was referred for assessment of a very low plasma HDL
      cholesterol and apolipoprotein AI concentration. At age 65, he had undergone
      triple vessel coronary bypass graft surgery. He had a strong family history of
      early coronary heart disease. We analyzed the molecular basis of his clinical and
      biochemical abnormalities. DESIGN AND METHODS: We used DNA sequencing to
      determine whether mutations in LCAT were present. We also evaluated plasma
      biochemistry and LCAT activity. RESULTS: DNA sequencing revealed that the patient
      was a heterozygote for the G30S mutation in the gene encoding lecithin:cholesteol
      acyl transferase (LCAT). His plasma was found to have half-normal LCAT activity.
      CONCLUSIONS: The findings in this patient suggest that rare dysfunctional
      mutations in candidate genes, such as LCAT, can contribute to the spectrum of
      patients ascertained because of low HDL cholesterol.

PMID- 11522276
TI  - An improved method for the rapid assessment of persisting chylomicron remnant
      concentrations.
AB  - Persisting chylomicron remnant concentrations have been linked to premature
      atherosclerosis. The analysis of persisting chylomicron remnant concentrations by
      an oral triglyceride tolerance test, however, is time-consuming for the study
      subjects and requires large resources in the laboratory. Therefore, only small
      numbers of subjects have been studied in the past. We describe major improvements
      of the testing procedure in regard of composition of the fatty meal, of patient
      testing, and measurement of postprandial remnants. Shifting the time of the
      (ready-to-use) fatty drink from the morning hours to bedtime was well accepted by
      the study subjects and allowed the analysis of blood samples drawn at the morning
      with minimal impact on the participants' time and with minimal interferences by
      confounding factors (e.g. smoking, additional food intake, physical activity).
      Chylomicron remnants were measured by fluorometry of the supernatant after
      ultracentrifugation. This procedure was sensitive, was specific for chylomicron
      remnants, and was easy to perform. The biological validity of the improved
      procedure was evaluated by studying type III hyperlipoproteinemia patients and
      normolipemic apolipoprotein (Apo) E2 homozygotes. In conclusion, this improved
      test permits the rapid testing for persisting chylomicron remnants in the
      clinical routine and in large epidemiological studies.

PMID- 11522277
TI  - Erythrocyte creatine as a marker of excessive erythrocyte destruction due to
      hypersplenism in patients with liver cirrhosis.
AB  - OBJECTIVE: Erythrocyte creatine is a sensitive marker of erythrocyte age, and can
      be used to detect slight and continuous hemolysis. Excessive blood cell
      destruction caused by increased spleen function is important evidence of
      hypersplenism. This study evaluates the usefulness of erythrocyte creatine as a
      sensitive marker of excessive erythrocyte destruction due to hypersplenism in
      patients with liver cirrhosis. DESIGN AND METHOD: Erythrocyte creatine was
      determined by an enzymatic method in 50 patients with postnecrotic liver
      cirrhosis and 50 healthy controls. The spleen size was measured by
      ultrasonography and expressed as a spleen index. RESULTS: The patients with
      splenomegaly showed significantly higher erythrocyte creatine than those without
      splenomegaly (p < 0.005) and healthy controls (p < 0.001), but there was no
      significant difference in erythrocyte creatine between healthy controls and those
      without splenomegaly. Fourteen (93%) of the 15 patients with abnormally high
      erythrocyte creatine (> 1.8 micromol/g hemoglobin) had splenomegaly. There were
      no significant differences in reticulocyte count between healthy controls and the
      patients with and without splenomegaly. Erythrocyte creatine showed good
      correlations with spleen index (r = 0.67; p < 0.001) and reticulocytes (r = 0.63;
      p < 0.001). CONCLUSIONS: Erythrocyte creatine can be used for predicting
      erythropoietic status and estimating hypersplenism in patients with liver
      cirrhosis.

PMID- 11522278
TI  - Determination of amino acids by ion-exchange chromatography on filter paper
      spotted blood samples stored at different temperatures and for different periods:
      comparison with capillary and venous blood.
AB  - OBJECTIVE: To determine whether the well-established filter paper spotted blood
      method used for the determination of some amino acids could be reliably used to
      measure all amino acids and whether amino acid results thus obtained are
      reproducible and comparable to the results obtained by measuring plasma amino
      acids in either capillary or venous blood. METHODS: This is a prospective study
      in which blood samples from a finger-prick were collected in capillary tubes and
      at the same time blotted on filter papers; another sample was taken from a vein,
      from 19 healthy volunteers aged between 18 and 24 yr after a strict 12-h
      overnight fast. Another 9 healthy adult volunteers provided blood samples on
      filter papers for the storage study; 9 samples were analyzed immediately; 9, 8
      and 4 samples were stored at -20 degrees C, -4 degrees C and room temperature
      respectively and analyzed after 14 days; 8 samples stored at -20 degrees C were
      analyzed after 4 weeks. RESULTS: Intra-sample reproducibility in the filter paper
      blood from the same individual was found to be mostly less than 20%, while for
      the capillary blood was less than 5%. The greatest variability was in cystine and
      methionine. There was no significant difference between results obtained from
      capillary blood and from venous blood, but there was a significant difference
      between amino acid concentrations in venous and capillary blood on the one hand
      and filter paper blood on the other. Storage at different temperatures and for a
      varied period of time showed little change except in serine, glutamate,
      ornithine, histidine, cystine and methionine. There was a 30% decrease in
      concentrations of most amino acids in filter paper blood when compared to
      capillary or venous blood probably because of loss in the extraction process.
      CONCLUSION: A new set of values for amino acids in filter paper blood in normal
      individuals is presented. Blood spotted filter paper could be used to screen
      practically all inborn errors of amino acid metabolism.

PMID- 11522279
TI  - Oxidative stress in polycystic ovary syndrome and its contribution to the risk of
      cardiovascular disease.
AB  - OBJECTIVES: To determine oxidant and antioxidant status in women with polycystic
      ovary syndrome (PCOS) and its contribution to the risk of cardiovascular disease.
      DESIGN AND METHODS: 27 women with PCOS were compared with regard to oxidant and
      antioxidant status with 18 age- and body mass index (BMI)-matched healthy.
      Oxidant status was evaluated by determination of erythrocyte malondialdehyde
      (MDA) concentration, while antioxidant status was evaluated by determination of
      erythrocyte reduced glutathione (GSH) concentration, and glutathione peroxidase
      (GSH-Px) and superoxide dismutase (SOD) activities. Area under curve (AUC) for
      glucose, AUC for insulin and the insulin sensitivity index (ISI) were calculated
      from two-hour OGTT. RESULTS: Women with PCOS were found to have higher AUC for
      glucose (p = 0.01), AUC for insulin (p < 0.001), MDA level (p = 0.009) and SOD
      activity (p = 0.04), and lower ISI (p < 0.001) and GSH level (p = 0.03) than the
      controls. In correlation analysis, a significant relationship was found between
      MDA levels and age (p < 0.01), BMI (p < 0.001), waist-to-hip ratio (p < 0.01),
      systolic and diastolic blood pressures (both p < 0.05), AUCs for glucose and
      insulin (both p < 0.05), ISI (r = -0.42, p < 0.05) and triglyceride (p < 0.01).
      CONCLUSIONS: An increase in oxidant status was found in women with PCOS, and this
      increase was related to central obesity, age, blood pressure, serum glucose,
      insulin and triglyceride levels and insulin resistance. In contrast, antioxidant
      status was observed to be insufficient. These findings suggest that increased
      oxidative stress may contribute to the increased risk of cardiovascular disease
      in women with PCOS.

PMID- 11522280
TI  - Do wine polyphenols modulate p53 gene expression in human cancer cell lines?
AB  - BACKGROUND: The p53 gene is an established tumor suppressor and an inducer of
      apoptosis. We here attempt to determine whether the putative anticarcinogenic
      properties attributed to red wine and its polyphenolic constituents depend, at
      least in part, upon their ability to modulate p53 expression in cancer cells.
      METHODS: Three human breast cancer cell lines (MCF-7, T47D; MDA-MB-486) and one
      human colon cancer cell line [Colo 320 HSR (+)] were treated for 24-h with each
      of four polyphenols [quercetin; (+)-catechin, trans-resveratrol; caffeic acid] at
      concentrations ranging from 10(-7) M to 10(-4) M, after which, p53 concentrations
      were measured in cell lysates by a time-resolved fluorescence immunoassay.
      RESULTS: None of the polyphenols tested affected p53 expression in the breast
      cancer cell lines T-47D and MDA-MB-486. p53 content of MCF-7 breast cancer cells
      (wild-type) was increased by caffeic acid, decreased by resveratrol, and showed a
      twofold increase with catechin, that reached borderline statistical significance;
      however, none of these effects were dose-responsive. Colo 320 HSR (+) cells (with
      a mutant p53 gene) had lower p53 content upon stimulation, reaching borderline
      statistical significance, but without being dose-responsive, in the presence of
      caffeic acid and resveratrol. Apart from toxicity at 10(-4) M, quercetin had no
      effect upon these four cell lines. CONCLUSIONS: The observed p53 concentration
      changes upon stimulation by polyphenols are relatively small, do not follow a
      uniform pattern in the four cell lines tested, and do not exhibit a dose-response
      effect. For these reasons, we speculate that the putative anticarcinogenic
      properties of wine polyphenols are unlikely to be mediated by modulation of p53
      gene expression.

PMID- 11522281
TI  - Serum cortisol/cortisone ratio after Synacthen stimulation.
AB  - OBJECTIVES: 11beta-Hydroxysteroid dehydrogenase (11beta-HSD) enzymes interconvert
      active cortisol and inactive cortisone. There is growing evidence that local
      tissue concentrations of cortisol are generally modulated by site specific
      different 11beta-HSD actions. While 11beta-HSD type 2 unidirectionally
      inactivates cortisol, type 1 isoform acts bidirectionally. 11beta-HSD type 1 is
      mainly localized in the liver and may thus restore circulating biologically
      inactive cortisone to active cortisol thereby modulating systemic glucocorticoid
      action; such a mechanism might be of importance in stressful situations. To study
      this hypothesis we investigated the influence of exogenous ACTH on serum
      cortisol/cortisone ratio. DESIGN AND METHODS: Paired serum samples that were
      submitted for routine analysis of cortisol before and 1 h after stimulation with
      250 microg ACTH (1-24) (Synacthen) were collected prospectively if the routine
      tests indicated normal adrenal function; 40 patients were included in the study,
      29 patients were female, 11 male, median age was 31 yr (range 14-70). Serum
      cortisol and cortisone were determined using LC-ESI/MS/MS with an online sample
      extraction system and tri-deuterated cortisol as the internal standard. RESULTS:
      While mean serum cortisol increased by 109% (mean basal concentration 373 nmol/L
      (SD 151 nmol/L), stimulated 781 nmol/L (SD 194 nmol/L)), mean serum cortisone
      significantly decreased after ACTH administration by 31% (p < 0.001, paired t
      test for differences). Mean serum cortisone was 70 nmol/L (SD 16 nmol/L) before
      and 48 nmol (SD 16 nmol/L) after ACTH administration; decrease in serum cortisone
      was observed in 34 (85%) of the patients. The ratio of serum cortisol/cortisone
      increased in all subjects (mean 5.4 (SD 1.9) before ACTH, and 16.2 (SD 6.2) after
      ACTH; p < 0.001). CONCLUSIONS: The data of our observational study suggest a
      modulation of peripheral metabolism of cortisol by ACTH with a stimulation of
      systemic 11beta-HSD type 1 activity, leading to restoration of inactive cortisone
      to biologically active cortisol.

PMID- 11522282
TI  - Pesticide induced alterations in acetylcholine esterase and gamma glutamyl
      transpeptidase activities and glutathione level in lymphocytes of human poisoning
      cases.

PMID- 11522283
TI  - Serum L-carnitine levels and lipoprotein compositions in chronic viral hepatitis
      patients.
AB  - OBJECTIVES: The aim of this study was to evaluate the serum L-carnitine levels
      and its effect on lipoproteins in chronic viral hepatitis B or C patients. DESIGN
      AND METHODS: Blood samples were taken from 41 patients and 30 healthy subjects
      after 12 h fasting. RESULTS: Patients' serum L-carnitine levels (11.19 +/- 6.67
      mg/L) (p < 0.0001) and hepatic enzyme activities (AST and ALT) (49.02 +/- 42.80
      and 58.35 +/- 57.51 U/L) (p < 0.0005) were significantly higher than controls'.
      Serum total (3.85 +/- 0.82 mmol/L), LDL (2.08 +/- 0.76 mmol/L) and HDL (1.02 +/-
      0.29 mmol/L) cholesterol levels were significantly lower in patients (p < 0.01).
      On the other hand triglyceride levels (1.65 +/- 0.85 mmol/L) were significantly
      higher in patients (p < 0.05). CONCLUSIONS: The higher L-carnitine levels of
      patients may result from the leakage of hepatic cellular carnitine. If there is a
      decreased hepatic cellular carnitine levels, this may affect the transport of
      acetyl moiety for cholesterol synthesis and alter lipoprotein composition.
      Further investigation is needed for hepatic tissue L-carnitine levels.

PMID- 11522284
TI  - Arginine and a polyarginine peptide inhibit alkaline phosphatase activity:
      possible consequences for cellular transport systems.

PMID- 11522285
TI  - Neurophilin-1 is a downstream target of transcription factor Ets-1 in human
      umbilical vein endothelial cells.
AB  - Transcription factor Ets-1 expressed in endothelial cells promotes angiogenesis.
      Here, we transiently overexpressed Ets-1 in human umbilical vein endothelial
      cells (HUVECs) and comprehensively searched for potential downstream targets of
      Ets-1 by cDNA microarray analysis. The expression of several angiogenesis-related
      genes including neuropilin-1 was augmented by the overexpression of Ets-1.
      Quantitative real-time RT-PCR and Western blotting confirmed the increase in the
      levels of neuropilin-1 mRNA and protein. In contrast, dominant negative ets-1
      decreased the levels of neuropilin-1 mRNA and protein. These results indicate
      that neuropilin-1 is a downstream target of Ets-1 in HUVECs.

PMID- 11522286
TI  - Calcitermin, a novel antimicrobial peptide isolated from human airway secretions.
AB  - The human airways are protected from pathogenic colonization by a blanket of
      fluid impregnated with innate antimicrobial effector molecules. Among several
      previously uncharacterized components, we isolated a peptide that had activity
      primarily targeting Gram-negative bacteria. We named the peptide 'calcitermin'
      since its amino acid sequence and mass were equivalent to the 15 C-terminal
      residues of the S100 protein, calgranulin C. The antimicrobial activity of
      calcitermin was enhanced in acidic buffers (pH 5.4) and in the presence of
      micromolar concentrations of ZnCl(2). Analysis revealed a putative zinc-binding
      consensus sequence as well as an alpha-helical conformation in structure
      promoting solvents.

PMID- 11522287
TI  - The Candida albicans Na(+)/H(+) antiporter exports potassium and rubidium.
AB  - The Candida albicans Cnh1p belongs to the family of Na(+)/H(+) antiporters (TC
      2.A.36) but it transports besides toxic sodium and lithium also rubidium and
      potassium. Upon heterologous expression in a Saccharomyces cerevisiae salt
      sensitive strain, the Cnh1p is targeted to the plasma membrane and its transport
      activity results in increased tolerance of cells to external alkali metal
      cations. The cation efflux activity of Cnh1p in S. cerevisiae depends on the
      gradient of protons across the plasma membrane, and a Cnh1p-mediated K(+) efflux
      is involved in a cell response to sudden rise of cytoplasmic pH.

PMID- 11522288
TI  - Multiple phosphorylation sites in RGS16 differentially modulate its GAP activity.
AB  - Regulators of G-protein signaling (RGS) are GTPase-activating proteins (GAP) for
      activated Galpha subunits. We found that mouse RGS16, when expressed in HEK293T
      cells, is phosphorylated constitutively at serine 194 based on in vivo
      orthophosphate labeling experiments, while serine 53 is phosphorylated in a
      ligand-dependent manner upon stimulation by epinephrine in cells expressing the
      alpha2A adrenergic receptor. Phosphorylation on both sites impairs its GAP
      activity and subsequent attenuation on heterotrimeric G-protein-stimulated
      extracellular signal-regulated protein kinase activity. This is the first report
      of RGS functional downregulation by phosphorylation via a G-protein-coupled
      receptor.

PMID- 11522289
TI  - Probing into the function of the gene product responsible for glycogen storage
      disease type Ib.
AB  - This study aimed at directly assessing glucose 6-phosphate (G6P) transport by
      intact rat liver microsomes. Tracer uptake from labeled G6P occurred with T(1/2)
      values that proved insensitive to unlabeled G6P or 100 microM vanadate, and could
      not be activated over background levels by intravesicular phosphate in the
      complete absence of G6P hydrolysis. [(32)P]Phosphate efflux was similarly
      unaffected by G6P or phosphate in the incubation medium. We conclude that the
      gene product responsible for glycogen storage disease type Ib is functionally
      distinct from the bacterial hexose phosphate transporter, which operates as an
      obligatory phosphate:phosphate or G6P:phosphate exchanger.

PMID- 11522290
TI  - Evidence of a tissue-restricting DNA regulatory element in the mouse IRBP
      promoter.
AB  - The expression of interphotoreceptor retinoid binding protein (IRBP) is limited
      to photoreceptor cells of the retina and pinealocytes of the pineal gland. We
      sought to define cis-elements of the mouse IRBP 5' flanking region that are
      required for this restricted activity. In vitro transient transfections of
      retinoblastoma and neuroblastoma cells and in vivo experiments with transgenic
      Xenopus laevis indicate that -1783/+101 and -156/+101 IRBP gene fragments
      directed expression predominantly to the retina and pineal, with minor neuronal
      expression elsewhere. In contrast, a -70/+101 fragment was less restrictive in
      controlling expression, exhibiting activity not only in retina, but also in
      forebrain, hindbrain, spinal cord, and motor neurons innervating gills.

PMID- 11522291
TI  - Requirement of ceramide for adhesion of Helicobacter pylori to
      glycosphingolipids.
AB  - Direct adhesion of Helicobacter pylori to immobilized glycosphingolipids (GSLs)
      was compared to that of their corresponding oligosaccharide-conjugated
      neoglycoconjugates in order to clarify the roles of the carbohydrate and lipid
      portions of GSLs in H. pylori adhesion. These bacteria were found to adhere to
      sulfatide, GM3, GalCer and LacCer, but not to ceramide, sphingomyelin, or
      polyacrylamides conjugated with beta-galactose, lactose, 3'-sialyllactose or 3'
      sulfo-beta-galactose. Furthermore, neoglycolipids or bovine serum albumin
      derivatives with corresponding oligosaccharides were unable to serve as the
      ligands. H. pylori adhesion to GalCer with alpha-hydroxyl fatty acid was much
      stronger than GalCer with the non-hydroxyl fatty acid. These results suggest that
      H. pylori recognize the conformation of GSL with alpha-hydroxyl fatty acid on
      solid phase.

PMID- 11522293
TI  - The protease inhibitor chagasin of Trypanosoma cruzi adopts an immunoglobulin
      type fold and may have arisen by horizontal gene transfer.
AB  - Chagasin, a protein from Trypanosoma cruzi, is the first member of a new family
      of tight binding cysteine protease inhibitors [Monteiro, A.C.S., Abrahamson, M.,
      Lima, A.P.C., Vannier-Santos, M.A. and Scharfstein, J. (2001) J. Cell Sci., in
      press] [corrected]. Despite its lack of significant sequence identity with known
      proteins, convincing structural models, using variable light chain templates,
      could be constructed on the basis of threading results. Experimental support for
      the final structure came from inhibition data for overlapping oligopeptides
      spanning the chagasin sequence. Chagasin therefore exemplifies a new protease
      inhibitor structural class and a new natural use for an immunoglobulin-like
      domain. Limited sequence resemblance suggests that chagasin may represent the
      result of a rare horizontal gene transfer from host to parasite.

PMID- 11522292
TI  - Pregnancy-associated plasma protein-A (PAPP-A) cleaves insulin-like growth factor
      binding protein (IGFBP)-5 independent of IGF: implications for the mechanism of
      IGFBP-4 proteolysis by PAPP-A.
AB  - Pregnancy-associated plasma protein-A (PAPP-A) has recently been identified as
      the proteinase responsible for cleavage of insulin-like growth factor binding
      protein (IGFBP)-4, an inhibitor of IGF action, in several biological fluids.
      Cleavage of IGFBP-4 by PAPP-A is believed to occur only in the presence of IGF.
      We here report that in addition to IGFBP-4, PAPP-A also cleaves IGFBP-5. Cleavage
      occurs at one site, between Ser-143 and Lys-144 of IGFBP-5. In the presence of
      IGF, IGFBP-4 and -5 are cleaved with similar rates by PAPP-A. Interestingly,
      cleavage of IGFBP-5 by PAPP-A does not require the presence of IGF, but is
      slightly inhibited by IGF. These findings have implications for the mechanism of
      proteolysis of IGFBP-4 by PAPP-A, suggesting that IGFBP-4 binds IGF, which then
      becomes a PAPP-A substrate. Using highly purified, recombinant proteins, we
      establish that (1) PAPP-A cleavage of IGFBP-4 can occur in the absence of IGF,
      although the rate of hydrolysis is very slow, and (2) IGF is unable to bind to
      PAPP-A. We thus conclude that IGF enhances proteolysis by binding to IGFBP-4, not
      by interaction with PAPP-A, which could not previously be ruled out.

PMID- 11522294
TI  - Apolipoprotein E isoform-specific disruption of phosphoinositide hydrolysis:
      protection by estrogen and glutathione.
AB  - The mechanism(s) by which the E4 isoform of apolipoprotein E (apoE4) influences
      Alzheimer's disease (AD) are not fully known. We report that apoE4, but not
      apoE3, disrupts carbachol-stimulated phosphoinositide (PI) hydrolysis in SH-SY5Y
      neuroblastoma cells. Carbachol responses were also disrupted by beta-amyloid
      (Abeta) (1-42) and apoE4/Abeta(1-42) complexes, but not by apoE3/Abeta(1-42).
      Glutathione and estrogen protected against apoE4 and Abeta(1-42) effects, as well
      as those of H(2)O(2). Estrogen protection was partially blocked by wortmannin,
      suggesting the involvement of phosphatidylinositol 3-kinase. An apoE4-induced
      disruption of acetylcholine muscarinic receptor-mediated signalling may explain
      the lower effectiveness of cholinergic replacement treatments in apoE4 AD
      patients. Also, the beneficial effect of estrogen in AD may be partially due to
      its ability to protect against apoE4- and Abeta(1-42)-mediated disruption of PI
      hydrolysis.

PMID- 11522295
TI  - Nitric oxide enhances MPP(+) inhibition of complex I.
AB  - There is evidence that 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP)
      toxicity is mediated through both inhibition of mitochondrial complex I and free
      radical generation. 7-Nitroindazole protects against MPTP toxicity in vitro and
      in vivo, and this appears to be related to its inhibition of nitric oxide (NO(*
      )) synthase. We now show that the NO(*-) generator, glutathione-N-oxide, enhances
      the inhibitory action of 1-methyl-4-phenylpyridinium (MPP(+)) on complex I
      activity in brain submitochondrial particles. We propose that the NO(*-)-induced
      reversible inhibition of complex IV (cytochrome oxidase) potentiates the MPP(+)
      induced irreversible free radical-mediated inhibition of complex I. Thus, NO(*-)
      may 'prime' the respiratory chain to the effects of MPP(+). These data provide
      evidence for an interaction between NO(*-) and MPP(+) at the level of the
      respiratory chain.

PMID- 11522296
TI  - Proteasome inhibitors induce Fas-mediated apoptosis by c-Myc accumulation and
      subsequent induction of FasL message in human glioma cells.
AB  - Proteasome inhibitors were shown previously to induce mitochondria-independent
      and caspase-3-dependent apoptosis in human glioma cell lines by unknown
      mechanisms. Here, we showed that treatment with proteasome inhibitors,
      lactacystin or acetyl-leucinyl-leucinyl-norleucinal, led to elevation of the
      steady-state c-Myc protein but not c-myc mRNA, suggesting the accumulation of c
      Myc protein by proteasome inhibitors. In addition, the marked association of c
      Myc protein with ubiquitin by treatment with proteasome inhibitors indicated the
      involvement of proteasome in c-Myc proteolysis and the stabilization of c-Myc
      protein by proteasome inhibitors in vivo. The expression of Fas (also termed CD95
      or APO-1) mRNA, if analyzed by reverse transcriptase polymerase chain reaction
      assay, was found to occur constitutively, and increased slightly by the treatment
      with proteasome inhibitors. In contrast, the expression of Fas ligand (FasL) mRNA
      was markedly induced temporarily before the activation of caspase-3 by the
      treatment. Agonistic anti-Fas antibody (CH11) induced apoptotic cell death,
      suggesting the presence of a functional Fas receptor. In addition, proteasome
      inhibitor-induced apoptosis was prevented by the addition of antagonistic anti
      FasL antibody (4A5) or z-IETD.fmk, a potent inhibitor of caspase-8, indicating
      the involvement of the Fas receptor-ligand apoptotic signaling system in
      proteasome inhibitor-mediated apoptosis. Thus, it is suggested that proteasome
      inhibitors cause the accumulation of c-Myc protein which induces transiently FasL
      message to stimulate the Fas receptor-ligand apoptotic signaling pathway.

PMID- 11522297
TI  - An internal segment (residues 58-119) of the hepatitis B virus X protein is
      sufficient to activate MAP kinase pathways in mouse liver.
AB  - The human hepatitis B virus X protein (HBx) is known as a dual-specificity
      transactivator stimulating the transcriptional machinery in the nucleus and
      signal transduction pathways in the cytoplasm. HBx-induced activation of mitogen
      activated protein kinase (MAPK) signaling cascades is considered to play an
      important role in hepatitis B virus-mediated hepatocarcinogenesis. Herein, we
      have identified the regions of HBx that are crucial for activating such signaling
      cascades in vivo. A truncated mutant incorporating regions C-E (amino acids 58
      140) was as effective as the full-length HBx in activating MAPKs and enhancing
      activator protein-1 binding activity. While deletion of region C (amino acids 58
      84) or D (amino acids 85-119) led to a drastic loss of function, region E (amino
      acids 120-140) was dispensable for the activation of signaling cascades. Overall,
      these findings provide the first evidence for the requirement of domain 58-119 of
      HBx in transmitting mitogenic signals to the nucleus in vivo.

PMID- 11522298
TI  - Lectin-like oxidized low density lipoprotein receptor-1 (LOX-1) supports cell
      adhesion to fibronectin.
AB  - Lectin-like oxidized lipoprotein receptor-1 (LOX-1) is a specific receptor for
      atherogenic oxidized low density lipoprotein (OxLDL) which belongs to the
      scavenger receptor family. In the present report, we show that LOX-1 can also
      support cell adhesion to fibronectin (FN) in a divalent cation-independent
      fashion. CHO-K1 cells stably expressing bovine LOX-1 (BLOX-1-CHO), but not
      untransfected CHO-K1 cells, can adhere to FN-coated plates, but not to collagen
      coated plates, in the presence of EDTA. BLOX-1-CHO adhesion to FN-coated plates
      can also be suppressed by scavenger receptor ligands, such as OxLDL, polyinosinic
      acid (poly I), and dextran sulfate, but not by native LDL, acetylated LDL,
      polycytidylic acid (poly C), or chondroitin sulfate. Cultured bovine aortic
      endothelial cells can similarly adhere to FN-coated plates, which was inhibited
      by OxLDL, poly I, and dextran sulfate in the presence of EDTA. LOX-1 may play an
      important role in cell adhesion to FN in an integrin-independent manner.

PMID- 11522299
TI  - The Pla surface protease/adhesin of Yersinia pestis mediates bacterial invasion
      into human endothelial cells.
AB  - The plasminogen activator Pla of Yersinia pestis belongs to the omptin family of
      enterobacterial surface proteases and is responsible for the highly efficient
      invasion of the plague bacterium from the subcutaneous infection site into the
      circulation. Y. pestis has been reported to invade human epithelial cells. Here,
      we investigated the role of Pla in bacterial invasion into human endothelial
      cells. Expression of Pla in recombinant Escherichia coli XL1(pMRK1) enhanced
      bacterial invasion into ECV304 cells. The invasiveness was not affected by
      substitution mutation at the residues S99 or D206 that are needed for the
      proteolytic activity of Pla. Pla-expressing bacteria adhered to the extracellular
      matrix of ECV304 cells. Only weak adhesion and poor invasion were seen with the
      recombinant E. coli XL1(pMRK2), which expresses the omptin homolog from E. coli.
      The results identify Pla as an invasion protein of Y. pestis and show that the
      invasive function does not involve the proteolytic activity of Pla.

PMID- 11522300
TI  - Phosphatidylserine induces apoptosis in CHO cells without mitochondrial
      dysfunction in a manner dependent on caspases other than caspases-1, -3, -8 and 
      9.
AB  - Treatment of Chinese hamster ovary K1 cells with phosphatidylserine (PS) caused
      typical apoptosis with distinct morphological and biochemical features in a dose-
      and time-dependent manner. However, unlike camptothecin-induced apoptosis,
      changes in mitochondrial transmembrane potential were not observed. In addition,
      cytochrome c release did not occur in PS-induced apoptosis. A pan caspase
      inhibitor, Z-VAD, significantly inhibited the apoptosis, but inhibitors of
      caspase-1, -3, -8 and -9 did not. Activities of caspase-1, -3, -8 and -9 were
      increased by treatment of the cells with camptothecin, but not with PS. These
      results suggest that PS-induced apoptosis occurs without the collapse of
      mitochondrial transmembrane potential and without the release of cytochrome c, in
      a manner independent of caspase-1, -3, -8 and -9.

PMID- 11522302
TI  - Binding specificity of siglec7 to disialogangliosides of renal cell carcinoma:
      possible role of disialogangliosides in tumor progression.
AB  - Previous studies indicate that expression of higher gangliosides in renal cell
      carcinoma (RCC) is correlated with metastatic potential, particularly in the
      lung. Out of five major gangliosides in RCC, three disialogangliosides
      (disialogalactosylgloboside, IV(3)NeuAcIII(6)NeuAcLc(4), and
      IV(4)GalNAcIV(3)NeuAcIII(6)NeuAcLc(4)) bind strongly to siglec7, which is
      expressed highly in monocytes and natural killer cells. Out of other gangliosides
      tested, 2-->6 sialylparagloboside, GD3, GD2, and GT1b, but not other lacto- or
      ganglio-series gangliosides, showed clear binding to siglec7. In view of
      preferential metastasis of RCC to the lung, and binding of RCC cell line TOS-1 to
      lung tissue sections as shown in our previous study, we examined expression of
      siglec7 in the lung. siglec7 is expressed highly in resident blood cells, but not
      in parenchymatous cells. TOS-1 cells aggregate together strongly through adhesion
      with peripheral blood mononuclear cells to form large clumps. This suggests the
      possibility that such aggregates may form embolisms of microvasculature,
      particularly in the lung, which initiate metastasis. Other possible roles of
      higher gangliosides in RCC in promoting metastasis and tumor progression are
      discussed.

PMID- 11522303
TI  - Numerical investigation of physiologically realistic pulsatile flow through
      arterial stenosis.
AB  - Numerical simulations of pulsatile blood flow in straight tube stenosis models
      were performed to investigate the poststenotic flow phenomena. In this study,
      three axisymmetrical and three asymmetrical stenosis models with area reduction
      of 25%, 50% and 75% were constructed. A measured human common carotid artery
      blood flow waveform was used as the upstream flow condition which has a mean
      Reynold's number of 300. All calculations were performed with high spatial and
      temporal resolutions. Flow features such as velocity profiles, flow separation
      zone (FSZ), and wall shear stress (WSS) distributions in the poststenotic region
      for all models are presented. The results have demonstrated that the formation
      and development of FSZs in the poststenotic region are very complex, especially
      in the flow deceleration phase. In axisymmetric stenoses the poststenotic flow is
      more sensitive to changes in the degree of stenosis than in asymmetric models.
      For severe stenoses, the stenosis influence length is shorter in asymmetrical
      models than in axisymmetrical cases. WSS oscillations (between positive and
      negative values) have been observed at various downstream locations in some
      models. The amplitude of the oscillation depends strongly on the axial location
      and the degree of stenosis.

PMID- 11522304
TI  - Sensitivity of predicted muscle forces to parameters of the optimization-based
      human leg model revealed by analytical and numerical analyses.
AB  - There are different opinions in the literature on whether the cost functions: the
      sum of muscle stresses squared and the sum of muscle stresses cubed, can
      reasonably predict muscle forces in humans. One potential reason for the
      discrepancy in the results could be that different authors use different sets of
      model parameters which could substantially affect forces predicted by
      optimization-based models. In this study, the sensitivity of the optimal solution
      obtained by minimizing the above cost functions for a planar three degrees-of
      freedom (DOF) model of the leg with nine muscles was investigated analytically
      for the quadratic function and numerically for the cubic function. Analytical
      results revealed that, generally, the non-zero optimal force of each muscle
      depends in a very complex non-linear way on moments at all three joints and
      moment arms and physiological cross-sectional areas (PCSAs) of all muscles.
      Deviations of the model parameters (moment arms and PCSAs) from their nominal
      values within a physiologically feasible range affected not only the magnitude of
      the forces predicted by both criteria, but also the number of non-zero forces in
      the optimal solution and the combination of muscles with non-zero predicted
      forces. Muscle force magnitudes calculated by both criteria were similar. They
      could change several times as model parameters changed, whereas patterns of
      muscle forces were typically not as sensitive. It is concluded that different
      opinions in the literature about the behavior of optimization-based models can be
      potentially explained by differences in employed model parameters.

PMID- 11522305
TI  - Strategies of muscular support of varus and valgus isometric loads at the human
      knee.
AB  - In this paper we studied how subjects activate their muscles in response to
      static varus and valgus loads at the knee. The muscles' contributions to the
      external moments were estimated using an EMG driven biomechanical model of the
      knee. The individual muscle activation and loading patterns were examined to
      identify the strategies that the nervous system uses to support varus and valgus
      knee moments. It was found that the (1) co-contraction of the hamstrings and
      quadriceps, and (2) activation of the gracilis and tensor fascia lata increased
      with the increasing magnitude of the varus and valgus moments. These 2 activation
      patterns provided positive support of valgus and varus loads at the knee The
      sartorius appears to be activated to provide positive support of valgus loads at
      the knee, whereas during varus moments this muscle increases the varus load on
      the knee, i.e. provides negative support. Generally, the hamstrings and
      quadriceps co-contraction contributed to most of the muscular support of the
      varus and valgus moments. In addition, co-contraction supported 11-14% of the
      external moment in pure varus and pure valgus respectively. It appears that there
      are activation strategies with the specific purpose to support varus and valgus
      moments, albeit small, which suggest dual goals of the neuromotor system during
      the support of varus and valgus moments.

PMID- 11522306
TI  - 3D-finite element analyses of cusp movements in a human upper premolar, restored
      with adhesive resin-based composites.
AB  - The combination of diverse materials and complex geometry makes stress
      distribution analysis in teeth very complicated. Simulation in a computerized
      model might enable a study of the simultaneous interaction of the many variables.
      A 3D solid model of a human maxillary premolar was prepared and exported into a
      3D-finite element model (FEM). Additionally, a generic class II MOD cavity
      preparation and restoration was simulated in the FEM model by a proper choice of
      the mesh volumes. A validation procedure of the FEM model was executed based on a
      comparison of theoretical calculations and experimental data. Different
      rigidities were assigned to the adhesive system and restorative materials. Two
      different stress conditions were simulated: (a) stresses arising from the
      polymerization shrinkage and (b) stresses resulting from shrinkage stress in
      combination with vertical occlusal loading. Three different cases were analyzed:
      a sound tooth, a tooth with a class II MOD cavity, adhesively restored with a
      high (25 GPa) and one with a low (12.5GPa) elastic modulus composite. The cusp
      movements induced by polymerization stress and (over)-functional occlusal loading
      were evaluated. While cusp displacement was higher for the more rigid composites
      due to the pre-stressing from polymerization shrinkage, cusp movements turned out
      to be lower for the more flexible composites in case the restored tooth which was
      stressed by the occlusal loading. This preliminary study by 3D FEA on adhesively
      restored teeth with a class II MOD cavity indicated that Young's modulus values
      of the restorative materials play an essential role in the success of the
      restoration. Premature failure due to stresses arising from polymerization
      shrinkage and occlusal loading can be prevented by proper selection and
      combination of materials.

PMID- 11522308
TI  - A novel low wearing differential hardness, ceramic-on-metal hip joint prosthesis.
AB  - Osteolysis and loosening of artificial joints caused by polyethylene wear debris
      has prompted renewed interest in alternative bearing materials for hip prosthesis
      designs. Lower wearing metal-on-metal (MOM) and ceramic-on-ceramic prostheses are
      being used more extensively, and there is considerable interest in further
      improving on their performance. This study investigated the wear properties and
      debris morphology of a novel differential hardness ceramic-on-metal (COM)
      prosthesis, in comparison with MOM articulations in a physiological anatomical
      hip joint simulator. The COM pairings were found to have wear rates approximately
      100-fold lower than the MOM pairings. The MOM pairings showed a higher "bedding
      in" wear rate (3.09+/-0.46mm(3)/10(6) cycles) in the first million cycles, which
      then reduced to a steady state wear rate of 1.23+/-0.5mm(3)/10(6) cycles. The
      wear rate of the COM pairings over the duration of the test was approximately
      0.01mm(3)/10(6) cycles with very little wear detected on the surface of the
      prosthesis components. The wear particles from both articulations were oval to
      round in shape and in the nanometer size range. After one million cycles the mean
      maximum diameter of the MOM and COM wear particles were 30+/-2.25 and 17.57+/
      1.37nm, respectively. After five million cycles the wear particles were
      statistically significantly smaller than at one million cycles, 13.9+/-0.72nm for
      the MOM pairings and 6.11+/-0.40nm for the COM pairings. The wear rates of the
      MOM prostheses were representative of clinical values. The use of differential
      hardness COM pairings dramatically reduced the wear rate compared to MOM hip
      prostheses. The wear particles from the MOM articulation were similar to
      particles found in retrieved tissues from around MOM prostheses. The extremely
      low wearing differential hardness COM bearings presented in this study produced
      far smaller volumetric particle loads compared to MOM prostheses currently used
      clinically.

PMID- 11522307
TI  - A nonlinear anisotropic model for porcine aortic heart valves.
AB  - The anisotropic property of porcine aortic valve leaflet has potentially
      significant effects on its mechanical behaviour and the failure mechanisms.
      However, due to its complex nature, testing and modelling the anisotropic porcine
      aortic valves remains a continuing challenge to date. This study has developed a
      nonlinear anisotropic finite element model for porcine heart valves. The model is
      based on the uniaxial experimental data of porcine aortic heart valve leaflet and
      the properties of nonlinear composite material. A finite element code is
      developed to solve this problem using the 8-node super-parameter nonlinear shells
      and the update Lagrangian method. The stress distribution and deformation of the
      porcine aortic valves with either uniform and non-uniform thicknesses in closed
      phase and loaded condition are calculated. The results showed significant changes
      in the stress distributions due to the anisotropic property of the leaflets.
      Compared with the isotropic valve at the same loading condition, it is found that
      the site of the peak stress of the anisotropic leaflet is different; the maximum
      longitudinal normal stress is increased, but the maximum transversal normal
      stress and in-plane shear stress are reduced. We conclude that it is very
      important to consider the anisotropic property of the porcine heart valves in
      order to understand the failure mechanism of such valves in vivo.

PMID- 11522309
TI  - Kinematic analysis of a multi-segment foot model for research and clinical
      applications: a repeatability analysis.
AB  - An unbiased understanding of foot kinematics has been difficult to achieve due to
      the complexity of foot structure and motion. We have developed a protocol for
      evaluation of foot kinematics during barefoot walking based on a multi-segment
      foot model. Stereophotogrammetry was used to measure retroreflective markers on
      three segments of the foot plus the tibia. Repeatability was evaluated between
      trial, between-day and between-tester using two subjects and two testers. Subtle
      patterns and ranges of motion between segments of the foot were consistently
      detected. We found that repeatability between different days or different testers
      is primarily subject to variability of marker placement more than inter-tester
      variability or skin movement. Differences between inter-segment angle curves
      primarily represent a shift in the absolute value of joint angles from one set of
      trials to another. In the hallux, variability was greater than desired due to
      vibration of the marker array used. The method permits objective foot measurement
      in gait analysis using skin-mounted markers. Quantitative and objective
      characterisation of the kinematics of the foot during activity is an important
      area of clinical and research evaluation. With this work we hope to have provided
      a firm basis for a common protocol for in vivo foot study.

PMID- 11522310
TI  - Lumbar back muscle activity of helicopter pilots and whole-body vibration.
AB  - Several studies have attributed the prevalence of low back pain (LBP) in
      helicopter pilots mainly to poor posture in-flight and whole-body vibration, with
      the latter hypothesis particularly related to a cyclic response of the erector
      spine (ES) muscle to vibration. This work aims to determine if helicopter
      vibration and the pilot's normal posture during flight have significant effects
      on the electromyogram (EMG) of the ES muscle. The bilateral surface EMG of the ES
      muscle at the L3 level was collected in 10 young pilots before and during a short
      flight in UH-50 helicopters. The vibration was monitored by a triaxial
      accelerometer fixed to the pilots' seat. Prior to the flight, the EMG was
      recorded for relaxed seated and standing postures with 0 degrees (P0) and 35
      degrees (P35) of trunk flexion. The effect of the posture during the flight was
      tested by comparing left and right EMG (normalized with respect to P35). The in
      flight muscle stress was evaluated by histograms of EMG activity, and compared to
      P0 values. Only one pilot in ten showed significant (p<0.05) correlation between
      the vibration and the EMG over cycles of vibration, and no consistent causal
      effect was found. The pilots' posture did not show significant asymmetric
      muscular activity, and low EMG levels were observed during most of the duration
      of the flight. The results do not provide evidence that LBP in helicopter pilots
      is caused by ES muscle stress in the conditions studied.

PMID- 11522311
TI  - Parametric finite element analysis of vertebral bodies affected by tumors.
AB  - The vertebral column is the most frequent site of metastatic involvement of the
      skeleton. Due to the proximity to the spinal cord, from 5% to 10% of all cancer
      patients develop neurologic manifestations. As a consequence, fracture risk
      prediction has significant clinical importance. In this study, we model the
      metastatically involved vertebra so as to parametrically investigate the effects
      of tumor size, material properties and compressive loading rate on vertebral
      strength. A two-dimensional axisymmetric finite element model of a spinal motion
      segment consisting of the first lumbar vertebral body (no posterior elements) and
      adjacent intervertebral disc was developed to allow the inclusion of a centrally
      located tumor in the vertebral body. After evaluating elastic, mixed, and
      poroelastic formulations, we concluded that the poroelastic representation was
      most suitable for modeling the metastatically involved vertebra's response to
      compressive load. Maximum principal strains were used to localize regions of
      potential vertebral trabecular bone failure. Radial and axial vertebral body
      displacements were used as relative indicators of spinal canal encroachment and
      endplate failure. Increased tumor size and loading rate, and reduced trabecular
      bone density all elevated axial and radial displacements and maximum tensile
      strains. The results of this parametric study suggest that vertebral tumor size
      and bone density contribute significantly to a patients risk for vertebral
      fracture and should be incorporated in clinical assessment paradigms.

PMID- 11522312
TI  - Stem surface roughness alters creep induced subsidence and 'taper-lock' in a
      cemented femoral hip prosthesis.
AB  - The clinical success of polished tapered stems has been widely reported in
      numerous long term studies. The mechanical environment that exists for polished
      tapered stems, however, is not fully understood. In this investigation, a
      collarless, tapered femoral total hip stem with an unsupported distal tip was
      evaluated using a 'physiological' three-dimensional (3D) finite element analysis.
      It was hypothesized that stem-cement interface friction, which alters the
      magnitude and orientation of the cement mantle stress, would subsequently
      influence stem 'taper-lock' and viscoelastic relaxation of bone cement stresses.
      The hypothesis that creep-induced subsidence would result in increases to stem
      cement normal (radial) interface stresses was also examined. Utilizing a
      viscoelastic material model for the bone cement in the analysis, three different
      stem-cement interface conditions were considered: debonded stem with zero
      friction coefficient (mu=0) (frictionless), debonded stem with stem-cement
      interface friction (mu=0.22) ('smooth' or polished) and a completely bonded stem
      ('rough'). Stem roughness had a profound influence on cement mantle stress, stem
      subsidence and cement mantle stress relaxation over the 24-h test period. The
      frictionless and smooth tapered stems generated compressive normal stress at the
      stem-cement interface creating a mechanical environment indicative of 'taper
      lock'. The normal stress increased with decreasing stem-cement interface friction
      but decreased proximally with time and stem subsidence. Stem subsidence also
      increased with decreasing stem-cement interface friction. We conclude that
      polished stems have a greater potential to develop 'taper-lock' fixation than do
      rough stems. However, subsidence is not an important determinant of the
      maintenance of 'taper-lock'. Rather subsidence is a function of stem-cement
      interface friction and bone cement creep.

PMID- 11522313
TI  - Resistance forces acting on suture needles.
AB  - Understanding the resistance forces encountered by a suture needle during tissue
      penetration is important for the development of robotic surgical devices and
      virtual reality surgical simulators. Tensile forces applied to skin and tendon
      during suturing were measured. Fresh sheep achilles tendons were tensioned with a
      static load 4.9 N, 9.8 N or 19.6 N and sheepskin with 0.98 N, 2.9 N or 4.9 N
      static load. A straight 2/0 cutting suture needle in series with a load cell on a
      materials testing machine penetrated the tissue at 90 degrees with a velocity of
      1, 5 or 10mm/s for each tissue tension (n=5). Continuous load versus displacement
      data was obtained and penetration load and stiffness were noted. The load versus
      displacement curve for skin during needle penetration demonstrated two
      characteristic peaks, corresponding to initial penetration and emergence of
      needle from the undersurface of the tissue. Increasing the tension within the
      tissue (skin and tendon) increased the amount of force required to penetrate the
      tissue with a suture needle (p<0.05). Needle displacement rate did not affect the
      resistance to needle penetration (p<0.05). This study provides a simple model for
      measuring force-feedback during needle penetration of soft tissues and is a good
      starting point for future studies of the penetration resistance properties of
      human tissues.

PMID- 11522314
TI  - Trabecular shear stress in human vertebral cancellous bone: intra- and inter
      individual variations.
AB  - Correlation of the mean and standard deviation of trabecular stresses has been
      proposed as a mechanism by which a strong relationship between the apparent
      strength and stiffness of cancellous bone can be achieved. The current study
      examined whether the relationship between the mean and standard deviation of
      trabecular von Mises stresses can be generalized for any group of cancellous
      bone. Cylindrical human vertebral cancellous bone specimens were cut in the
      infero-superior direction from T12 of 23 individuals (inter-individual group).
      Thirty nine additional specimens were prepared similarly from the T4-T12 and L2
      L5 vertebrae of a 63 year old male (intra-individual group). The specimens were
      scanned by micro-computed tomography (microCT) and trabecular von Mises stresses
      were calculated using finite element modeling. The expected value, standard
      deviation and coefficient of variation of the von Mises stress were calculated
      form a three-parameter Weibull function fitted to von Mises stress data from each
      specimen. It was found that the average and standard deviation of trabecular von
      Mises shear stress were: (i) correlated with each other, supporting the idea that
      high correlation between the apparent strength and stiffness of cancellous bone
      can be achieved through controlling the trabecular level shear stress variations,
      (ii) dependent on anatomical site and sample group, suggesting that the variation
      of stresses are correlated to the mean stress to different degrees between
      vertebrae and individuals, and (iii) dependent on bone volume fraction,
      consistent with the idea that shear stress is less well controlled in bones with
      low BV/TV. The conversion of infero-superior loading into trabecular von Mises
      stresses was maximum for the tissue at the junction of the thoracic and lumbar
      spine (T12-L1) consistent with this junction being a common site of vertebral
      fracture.

PMID- 11522315
TI  - An in situ calibration of an ultrasound transducer: a potential application for
      an ultrasonic indentation test of articular cartilage.
AB  - A change in mechanical properties of articular cartilage would be considered one
      of the most reliable signs of cartilage degeneration. While an indentation method
      has the potential to measure the cartilage properties in vivo, an accurate
      measurement of cartilage thickness in situ is technically difficult. An
      ultrasound transducer has often been used to measure the cartilage thickness.
      However, its accuracy is limited by the lack of an accurate measurement of the
      ultrasound speed of cartilage, for the ultrasound speed varies according to the
      pathological conditions of the tissue. Therefore, the objective of this study is
      to develop an in situ calibration method of predicting the true ultrasound speed
      of cartilage and thus allow the ultrasound transducer to measure the thickness of
      the tissue with great accuracy. By simultaneously implementing an indentation
      testing protocol using the ultrasound transducer as an indenter, this method can
      also provide an indentation stiffness measurement of cartilage. The feasibility
      of the proposed method was examined using normal and proteoglycan-depleted
      cartilage specimens. It was found that the true ultrasound speed measured by the
      in situ calibration method was sensitive to the proteoglycan depletion (1735+/-35
      m/s for normal, and 1598+/-28 m/s for proteoglycan-depleted cartilage), and that
      the measured cartilage thickness was consistently accurate regardless of the
      tissue condition. The measured indentation stiffness of articular cartilage was
      also sensitive to the tissue condition. Thus, this study demonstrates that the
      proposed ultrasonic indentation technique can be used to accurately identify the
      abnormality of articular cartilage in situ.

PMID- 11522316
TI  - Accuracy and repeatability of Roentgen stereophotogrammetric analysis (RSA) for
      measuring knee laxity in longitudinal studies.
AB  - Roentgen stereophotogrammetric analysis (RSA) can be used to assess temporal
      changes in anterior-posterior (A-P) knee laxity. However, the accuracy and
      precision of RSA is dependent on many factors and should be independently
      evaluated for a particular application. The objective of this study was to
      evaluate the use of RSA for measuring A-P knee laxity. The specific aims were to
      assess the variation or "noise" inherent to RSA, to determine the reproducibility
      of RSA for repeated A-P laxity testing, and to assess the accuracy of these
      measurements. Two experiments were performed. The first experiment utilized three
      rigid models of the tibiofemoral joint to assess the noise and to compare
      digitization errors of two independent examiners. No differences were found in
      the kinematic outputs of the RSA due to examiner, repeated trials, or the model
      used. In a second experiment, A-P laxity values between the A-P shear load limits
      of +/-60 N of five cadaver goat knees were measured to assess the error
      associated with repeated testing. The RSA laxity values were also compared to
      those obtained from a custom designed linkage system. The mean A-P laxity values
      with the knee 30 degrees, 60 degrees, and 90 degrees of flexion for the ACL
      intact goat knee (+/-95% confidence interval) were 0.8 (+/-0.25), 0.9 (+/-0.29),
      and 0.4 (+/-0.22) mm, respectively. In the ACL-deficient knee, the A-P laxity
      values increased by an order of magnitude to 8.8 (+/-1.39), 7.6 (+/-1.32), and
      3.1 (+/-1.20)mm, respectively. No significant differences were found between the
      A-P laxity values measured by RSA and the independent measurement technique. A
      highly significant linear relationship (r(2)=0.83) was also found between these
      techniques. This study suggests that the RSA method is an accurate and precise
      means to measure A-P knee laxity for repeated testing over time.

PMID- 11522317
TI  - A reevaluation and discussion on the threshold limit for hemolysis in a turbulent
      shear flow.
AB  - One major factor of red blood cell damage induced by artificial heart valves is
      the magnitude of turbulent shear stresses in the flow field. An often-cited
      threshold for hemolysis is 400 N/m(2) (Sallam and Hwang, Biorheology 21 (1984)
      783). This value, however, was measured with a one-component laser Doppler
      anemometer and was not calculated from the major principal Reynolds shear stress,
      therefore underestimating the threshold. This study performed flow field
      measurements under similar conditions, using a two-component laser Doppler
      anemometer and determining major principal Reynolds shear stress, to reevaluate
      the hemolytic threshold as 800 N/m(2) with an exposure time of 1 ms. The
      Kolmogorov length scales, approximately 9 microm, are capable of inflicting
      direct damage to the red blood cells. These results will serve as a more accurate
      reference in future heart valve design and testing.

PMID- 11522318
TI  - Passive transverse mechanical properties of skeletal muscle under in vivo
      compression.
AB  - The objective of the present study is to determine the passive transverse
      mechanical properties of skeletal muscle. Compression experiments were performed
      on four rat tibialis anterior muscles. To assess the stress- and strain
      distributions in the muscle during the experiment, a plane stress model of the
      cross section was developed for each muscle. The incompressible viscoelastic
      Ogden model was used to describe the passive muscle behaviour. The four material
      parameters were determined by fitting calculated indentation forces on measured
      indentation forces. The elastic parameters, mu and alpha, were 15.6+/-5.4 kPa and
      21.4+/-5.7, respectively. The viscoelastic parameters, delta and tau, were
      0.549+/-0.056 and 6.01+/-0.42 s. When applying the estimated material parameters
      in a three-dimensional finite element model, the measured behaviour can be
      accurately simulated.

PMID- 11522319
TI  - Decrease in level of APG-2, a member of the heat shock protein 110 family, in
      murine brain following systemic administration of kainic acid.
AB  - APG-2 belongs to the heat shock protein 110 family. Although kainic acid (KA)
      induced seizures are known to elicit expression of inducible heat shock protein
      70 (HSP70) in the brain, no investigation has been carried out on the APG-2 level
      after excitatory amino acid-induced seizures. By means of an immunoblot assay, we
      determined the levels of HSP70 and APG-2 in discrete brain structures of mice
      after a single intraperitoneal injection of KA or N-methyl-D-aspartic acid
      (NMDA). APG-2 level was significantly decreased in frontal cortex, hippocampus,
      and striatum three days after the administration of KA, while HSP70 level was
      increased in these regions following the administration. In any of these regions,
      APG-2 levels were returned to the control levels 10 days after the
      administration. However, no significant changes were observed in levels of both
      HSP70 and APG-2 in hypothalamus, midbrain, medulla-pons, and cerebellum of the
      mice. By contrast, NMDA administration did not significantly affect both levels
      in any of the regions examined. These findings indicate that the transient
      decrease in APG-2 expression is one of the intracellular events elicited by
      signals peculiar to KA, but not by those peculiar to NMDA, in telencephalon of
      murine brain.

PMID- 11522320
TI  - Repeated but not acute clomipramine decreases the effect of N-methyl-D-aspartate
      receptor activation on serotonergic transmission between the raphe nuclei and
      frontal cortex.
AB  - The effect of acute or repeated treatment with the antidepressant clomipramine
      (CIM) on N-methyl-D-aspartate (NMDA) evoked changes in extracellular 5
      hydroxytryptamine (5-HT) in the raphe nuclei and frontal cortex of the same rat
      has been studied using microdialysis. Acute injection of CIM (10 or 20 mg/kg)
      caused an increase in raphe extracellular 5-HT but did not significantly alter
      extracellular 5-HT in the frontal cortex. Infusion of 25 microM NMDA into the
      raphe decreased extracellular 5-HT in this region and increased terminal
      extracellular 5-HT in the frontal cortex. In contrast, infusion of 100 microM
      NMDA into the raphe was followed by an increase in local dialysate 5-HT and a
      decrease in 5-HT release in the cortex. When NMDA infusion, at either 25 or 100
      microM was preceded by one acute injection of CIM the effects of NMDA on 5-HT
      release in both brain structures were generally more marked than in vehicle
      injected controls. Repeated (15 day) treatment with CIM (10 or 20 mg/kg) caused a
      dose-dependent increase in basal extracellular 5-HT in both raphe and frontal
      cortex. In these animals, however, the effects of infusion of both 25 and 100
      microM NMDA on 5-HT release in raphe and frontal cortex were greatly attenuated
      or abolished. This suggests that adaptive functional changes occur in NMDA
      receptor function during treatment with an antidepressant. The possible
      significance of this in the aetiology and treatment of depression is discussed.

PMID- 11522321
TI  - Potentiation of NMDA receptor function through somatostatin release: a possible
      mechanism for the cognition-enhancing activity of GABA(B) receptor antagonists.
AB  - CGP 36742 is a weak GABA(B) receptor antagonist. However, it improves cognitive
      performances at low doses; it blocks GABA(B) receptors potently and selectively
      on somatostatinergic terminals; it prevents kynurenate from antagonising NMDA
      induced release of noradrenaline from rat brain slices potently. We here
      investigated whether and how somatostatin plays a role in the CGP 36742 activity.
      CGP 36742 increased the somatostatin-like immunoreactivity (SRIF-LI) release from
      hippocampal slices exposed to NMDA. In the kynurenate test with rat hippocampal
      slices SRIF-14 mimicked the effect of CGP 36742. CGP 36742 lost its activity in
      rats whose somatostatin content had been depleted with cysteamine. Exogenous SRIF
      14 reverted kynurenate antagonism in somatostatin-depleted slices. L362855, an
      sst(5) receptor agonist, but not the selective sst(1)-sst(4) agonists, L797591,
      L779976, L796778 and L803087, displayed activity in the kynurenate test. The
      effects of CGP 36742, SRIF-14 and L362855 were antagonised by the sst(5)
      preferring antagonist BIM-23056. The protein kinase C inhibitor GF 109203X
      prevented the reversal of the kynurenate antagonism by CGP 36742 or SRIF-14. In
      conclusion, by selectively blocking GABA(B) receptors on somatostatinergic
      terminals, CGP 36742 may disinhibit somatostatin release; the consequent
      activation of sst(5) receptors would potentiate the function of NMDA receptors
      coexisting with sst(5) receptors on noradrenergic neurons.

PMID- 11522322
TI  - Opioid and GABA receptors involved in mediation and modulation of tonic and
      stimulus-evoked inhibition of a spinal reflex in the decerebrated and spinalized
      rabbit.
AB  - The purposes of this study were to investigate: (i) the identity of the opioid
      peptide(s) mediating tonic and stimulus-evoked inhibition of the sural-medial
      gastrocnemius reflex of the decerebrated, spinalized rabbit and (ii) the
      modulation of these processes by endogenous GABA. The selective delta receptor
      antagonist naltrindole (100 nmol kg(-1) i.v.), the GABA(A) blocker bicuculline
      (300 nmol intrathecal, i.th.), and the GABA(B) antagonist CGP 35348 (1 micromol
      i.th.) increased gastrocnemius reflexes to 150-160% of pre-drug values, whereas a
      sub-maximal dose of naloxone (30 nmol kg(-1) i.v.) augmented reflexes to >500% of
      controls. Kelatorphan, an inhibitor of enkephalin metabolism (2 micromol i.th.),
      depressed gastrocnemius responses by 50% and potentiated the inhibitory effects
      of methionine enkephalin. Repetitive electrical stimulation of the superficial or
      common peroneal nerves inhibited reflexes for 15-20 min. This effect was
      significantly reduced by naltrindole and CGP 35348. It was not reduced by a low
      dose (30 nmol kg(-1) i.v.) of naloxone or by bicuculline. When naloxone and
      naltrindole were combined at 30 nmol kg(-1) each, stimulus-evoked inhibition was
      blocked. Given after bicuculline, naloxone at 100 nmol kg(-1) i.v. abolished
      peroneal-evoked inhibition, but a dose of 300 nmol kg(-1) was required to produce
      the same effect after CGP 35348. Kelatorphan augmented the depth and duration of
      inhibition evoked by peroneal nerve stimulation. These data are consistent with
      the involvement of enkephalin-like peptides in tonic and stimulus-evoked
      inhibition of the sural-gastrocnemius reflex. Tonic inhibition in rabbit spinal
      cord is dominated by opioids acting through mu receptors, whereas co-activation
      of delta, mu and GABA(B) receptors mediates stimulus-evoked inhibition. It is
      possible that GABA(B) receptors inhibit the release of spinal opioids while
      simultaneously supporting their actions at post-synaptic targets.

PMID- 11522323
TI  - Control of the efficiency of agonist-induced information transfer and stability
      of the ternary complex containing the delta opioid receptor and the alpha subunit
      of G(i1) by mutation of a receptor/G protein contact interface.
AB  - Fusion proteins were constructed between the delta opioid receptor and forms of
      the alpha subunit of G(i1) in which cysteine(351) was mutated to a range of amino
      acids. GDP reduced the binding of the agonist [(3)H]DADLE but not the antagonist
      [(3)H]naltrindole to both the receptor alone and all the delta opioid receptor
      Cys(351)XaaG(i1)alpha fusion proteins. For the fusion proteins the pEC(50) for
      GDP was strongly correlated with the n-octanol/H(2)O partition co-efficient of G
      protein residue(351). Fusion proteins in which this residue was either isoleucine
      or glycine had similar observed binding kinetics for [(3)H]DADLE. However, the
      rate of dissociation of [(3)H]DADLE was substantially greater for the glycine
      containing fusion protein than that containing isoleucine, indicating that more
      hydrophobic residues imbued greater stability to the agonist-receptor-G protein
      ternary complex. This resulted in a higher affinity of binding of [(3)H]DADLE to
      the fusion protein containing isoleucine(351). In expectation with the binding
      data, maximal DADLE-stimulated GTP hydrolysis by the isoleucine(351)-containing
      fusion protein was two-fold greater and the potency of DADLE seven-fold higher
      than for the version containing glycine. These results demonstrate that the
      stability of the ternary complex between delta opioid receptor, G(i1)alpha and an
      agonist (but not antagonist) ligand is dependent upon the nature of residue(351)
      of the G protein and that this determines the effectiveness of information flow
      from the receptor to the G protein.

PMID- 11522324
TI  - Ca(2+) influx through nonselective cation channels plays an essential role in
      endothelin-1-induced mitogenesis in C6 glioma cells.
AB  - Ca(2+) channels activated by endothelin-1 (ET-1) in C6 glioma cells (C6 cells)
      were characterized using whole-cell patch-clamps and by monitoring the
      intracellular free Ca(2+) concentration ([Ca(2+)](i)), when administering Ca(2+)
      channel blockers such as LOE 908 and SK&F 96365. Using this methodology, the
      Ca(2+) channels involved in ET-1-induced mitogenesis were identified. The patch
      clamp study and [Ca(2+)](i) monitoring showed that 10 nM ET-1 activated two types
      of Ca(2+)-permeable nonselective cation channels (NSCC); one was sensitive to LOE
      908 but resistant to SK&F 96365 (NSCC-1) and the other was sensitive to both LOE
      908 and SK&F 96365 (NSCC-2). Conversely, 0.1 nM ET-1 activated only NSCC-1.ET-1
      induced mitogenesis in a concentration-dependent manner, with the maximum effect
      arising at concentrations > or =10 nM. LOE 908 completely suppressed the 10 nM ET
      1-induced mitogenesis, whereas SK&F 96365 only partially suppressed it. The
      IC(50) values of these blockers for the ET-1-induced mitogenesis were similar to
      those for the 10 nM ET-1-induced increase in [Ca(2+)](i). In contrast, LOE 908
      completely suppressed 0.1 nM ET-1-induced mitogenesis, whereas SK&F 96365 did not
      affect it.Collectively, these results demonstrate that the sustained increase in
      [Ca(2+)](i), via NSCC-1 and NSCC-2, may be essential for ET-1-induced mitogenesis
      in C6 cells. Moreover, the sensitivity of NSCC-1 to ET-1 is higher than that of
      NSCC-2 to ET-1.

PMID- 11522325
TI  - Characterisation of [(125)I]-apamin binding sites in rat brain membranes with
      HE293 cells transfected with SK channel subtypes.
AB  - The pharmacology of [(125)I]-apamin binding sites was examined in rat cortical
      and hippocampal tissue and compared with membranes prepared from human embryonic
      kidney (HEK293) cells transfected with SK channel subtypes hSK1, rSK2 and rSK3.
      The K(D) of [(125)I]-apamin in rat cortex and hippocampus was similar to the
      apamin-sensitive subtypes, rSK2 and rSK3 (K(D) (pM): 6.4, 7.08, 6.56 and 8.94,
      respectively). In addition, [(125)I]-apamin had a K(D)=270.4pM for the putatively
      'apamin-insensitive' hSK1. Apamin had about a three-fold higher affinity than
      [(125)I]-apamin in brain tissue and in the cells expressing the different SK
      channel subtypes. Pancuronium, bicuculline and d-tubocurarine displayed
      micromolar affinity for all five-membrane preparations, whereas dequalinium and
      gallamine appear to show some subtype selectivity. Tetraethylammonium (TEA) and 4
      aminopyridine (4-AP) had millimolar affinity and linopirdine had no effect. In
      conclusion, the pharmacology of [(125)I]-apamin binding in the cortex and
      hippocampus was similar to that in the apamin-sensitive clones, rSK2 and rSK3. In
      addition, we demonstrated low affinity [(125)I]-apamin binding for hSK1 and
      identified compounds that show subtype selectivity. These data cast further doubt
      on the identification of SK1 as encoding for the K(+) channel responsible for the
      apamin-insensitive sAHP.

PMID- 11522326
TI  - Selective D3 receptor agonist effects of (+)-PD 128907 on dialysate dopamine at
      low doses.
AB  - An involvement of the D3 dopamine receptor in the modulation of extracellular
      dopamine concentrations is suggested by pharmacological studies. However, recent
      studies using D3 receptor knock out mice indicated that several functions
      previously attributed to the D3 receptor are mediated by other receptor types. In
      the present study, we used the no-net flux microdialysis technique to
      characterize: (i) basal dopamine dynamics in the ventral striatum of D3 knock out
      and wild type mice and (ii) the effects of the putative D3-receptor selective
      agonist (+)-PD 128907. Neither the extracellular dopamine concentration nor the
      in vivo extraction fraction, an indirect measure of basal dopamine uptake,
      differed between D3 knock out and wild type mice. Moreover, no differences in
      potassium (60 mM) or cocaine (5 or 20 mg/kg i.p.) evoked dopamine concentrations
      were detected between the two genotypes. However, intra-striatal or systemic
      administration of doses of (+)-PD 128907 that failed to modify dopamine
      concentrations in knock out mice significantly decreased dialysate dopamine
      concentrations in the wild type. Comparison of the concentration-response curve
      for (+)-PD 128907 revealed IC(25) values of 61 and 1327 nM in wild type and knock
      out mice, respectively, after intra-striatal infusions. Similar differences were
      obtained after systemic administration of the D3 preferring agonist (IC(25) 0.05
      and 0.44 mg/kg i.p. in wild type and knock out mice, respectively). We conclude
      that the activation of the D3 receptor decreases extracellular dopamine levels
      and that, at sufficiently low doses, the effects of (+)-PD 128907 on
      extracellular dopamine are selectively mediated by the D3 receptor.

PMID- 11522327
TI  - Effect of repeated treatment with tianeptine and fluoxetine on the central
      alpha(1)-adrenergic system.
AB  - Tianeptine (TIA) is an antidepressant drug which enhances the reuptake of
      serotonin but, in contrast to tricyclics, shows no affinity for neurotransmitter
      receptors. The present study was aimed at determining whether repeated TIA
      treatment induced adaptive changes in the alpha(1)-adrenergic system, similar to
      those reported by us earlier for tricyclic antidepressants. The experiments were
      carried out on male mice and rats. TIA was administered at a dose of 5 or 10mg/kg
      once or repeatedly (twice daily for 14 days) and fluoxetine (FLU), used as a
      reference compound, at a dose of 10mg/kg. The obtained results showed that TIA
      administered repeatedly potentiated the methoxamine- and phenylephrine (PHEN)
      induced exploratory hyperactivity in rats and clonidine-induced aggressiveness in
      mice, the effects mediated by alpha(1)-adrenoceptors. TIA given repeatedly (but
      not acutely) increased the binding (B(max)) of alpha(1)-adrenergic receptors in
      cerebral cortex for [(3)H]prazosin. However, the ability of the alpha(1)
      adrenoceptor agonist PHEN to compete for these sites was not significantly
      changed. The above results indicate that repeated TIA administration increases
      the responsiveness of the alpha(1)-adrenergic system (behavioural and biochemical
      changes). On the other hand, FLU did not affect any behavioural and biochemical
      changes in this system.

PMID- 11522328
TI  - Subunit-specific modulation of glycine receptors by neurosteroids.
AB  - The effects of pregnene and androstane steroids were studied on recombinant human
      glycine receptors (GlyRs) by whole-cell voltage-clamp electrophysiology. The
      3beta-sulphates of pregnenolone (PREGS) and dehydroepiandrosterone (DHEAS)
      inhibited GlyR currents with K(I) values of 2-20 microM for different (alpha(1),
      alpha(2), alpha(4) and beta) GlyR subunits. PREGS resulted in a parallel shift of
      the response curve of glycine for alpha(1) GlyRs. The inhibitory potencies of
      DHEAS relative to PREGS were decreased in transition from embryonic alpha(2)
      towards adult alpha(1)beta GlyRs. A decreased potency of DHEAS for alpha(4)
      versus alpha(2) GlyRs represents the first pharmacological difference reported
      between these subunits. A negative charge at C3 is required for GlyR antagonism
      but androsterone sulphate epimers at C3 inhibited without stereoselectivity. Some
      point mutations of alpha(1) GlyRs with characteristic functional consequences did
      not significantly affect the inhibitory potency of PREGS. Progesterone
      selectively inhibited alpha(2) GlyRs, while PREG and its acetic ester potentiated
      alpha(1) GlyRs. Coexpression of the alpha subunits with the beta subunit
      eliminated the enhancing effects of PREG and attenuated the inhibitory potencies
      of the neurosteroids. Based on these data we propose that neurosteroids might
      modulate perinatal GlyR activity and thereby influence neuronal development.

PMID- 11522329
TI  - Can gap-junction blockade preferentially inhibit neuronal hypersynchrony vs.
      excitability?
AB  - Epileptic activity involves a hypersynchronous firing of large populations of
      brain neurons, some of which are hyperexcitable. This study explored to what
      extent gap-junction blockade inhibits neuronal synchronization vs. neuronal
      excitability. We investigated the effects of the gap-junction blockers (GJBs) 1
      heptanol, 1-octanol and carbenoxolone vs. the loop diuretic furosemide on
      spontaneous and evoked epileptiform field potentials, induced in CA3 area of rat
      hippocampal slices by a 'high K(+)-low Ca(2+)' perfusion fluid. This milieu
      induced frequent (>30 min(-1)) spontaneous bursts, led single fimbrial stimuli to
      evoke repetitive population spikes (PSs), and increased PS amplitudes. Both
      furosemide and the three GJBs gradually reduced spontaneous field bursting, or
      even stopped it within one hour. The anti-bursting activity of carbenoxolone
      showed dose-response dependence in the concentration range 50-400 microM. 1
      heptanol and 1-octanol markedly and similarly depressed all the epileptiform
      markers of the evoked responses, whereas carbenoxolone did not reduce the number
      of repetitive PSs evoked by single stimuli. By its minor effect on evoked
      responses, carbenoxolone resembled furosemide, rather than its congeners GJBs.
      These results favor the possibility that selective gap-junction blockade might
      antagonize epileptic synchronization, without depressing neuronal excitability.

PMID- 11522330
TI  - Expression and regulation of phospholipase D during neuronal differentiation of
      PC12 cells.
AB  - To assess a possible role for phospholipase D (PLD) in PC12 cell signal
      transduction and differentiation, we have investigated the expression of PLD in
      PC12 cells and found that the differentiation factor, nerve growth factor (NGF)
      increased PLD1 protein expression and phorbol 12-myristate 13 acetate (PMA)
      induced PLD activity. During neuronal differentiation, this effect showed
      correlation to the protein expression levels of classical protein kinase C (PKC)
      isozymes, PKC-alpha and -beta II, but there was no significant increase in the
      protein level of RhoA, another regulatory factor for PLD activation.
      Interestingly, PLD1 was associated with PKC-alpha or beta II, and its association
      gradually increased as NGF-induced neuronal differentiation progressed. PKC
      inhibitor, Ro-31-8220, caused a significant inhibition of neurite outgrowth and
      PLD activity. Furthermore, PLD1 was constitutively associated with the Shc
      adaptor molecule, the overexpression of which is known to induce PLD activity and
      to induce neurite outgrowth. Taken together, the data in this study suggests that
      PLD1 is closely implicated in neuronal differentiation of PC12 cells.

PMID- 11522331
TI  - Effects of chronic Delta(9)-tetrahydrocannabinol treatment on hippocampal
      extracellular acetylcholine concentration and alternation performance in the T
      maze.
AB  - Delta(9)-Tetrahydrocannabinol (Delta(9)-THC), the psychoactive ingredient of
      cannabis sativa, reduces both extracellular hippocampal acetylcholine
      concentration and correct alternation tasks in the T-maze. The principal aim of
      this study was to determine whether a chronic Delta(9)-THC treatment would induce
      tolerance both to the reduction of extracellular hippocampal acetylcholine
      concentration and memory deficit produced by the drug. Our results show that a
      chronic Delta(9)-THC treatment (5mg/kg, i.p., twice daily for two weeks) did not
      produce tolerance to the inhibitory effects induced by the drug. Moreover, no
      strict temporal correlation between the two Delta(9)-THC effects was observed:
      the inhibition in extracellular acetylcholine concentration appeared only 80 min
      after treatment, while the reduction of correct alternation tasks in the T-maze
      began after 20 min. The cognitive and cholinergic effects induced by a chronic
      Delta(9)-THC treatment were completely blocked by the CB(1) cannabinoid receptor
      antagonist SR 141716A, indicating an involvement of CB(1) cannabinoid receptors
      in the persistent negative effects induced by the drug. These findings confirm
      the proposition that CB(1) cannabinoid receptors mediate the negative effects
      induced by Delta(9)-THC both on hippocampal extracellular acetylcholine
      concentration and correct alternation tasks in the T-maze, and they indicate that
      these effects may be differentiated. However, the major outcome of this work is
      the demonstration that no tolerance to the two inhibitory effects develops after
      a chronic Delta(9)-THC treatment.

PMID- 11522332
TI  - Behavioral and neurochemical changes following predatory stress in mice.
AB  - This article had several objectives. First it aimed at investigating the
      anxiogenic-like behaviors elicited by unavoidable cat exposure and/or cat odor
      across nine strains of mice (BALB/c, C57BL/6, C3H, CBA, DBA/2, NMRI, NZB, SJL,
      Swiss) in a modified version of the free-exploration test. The second objective
      was to investigate possible neurochemical changes following cat exposure in Swiss
      mice by measuring the turnover of dopamine (DA), noradrenaline (NA) and serotonin
      (5-HT) in several brain regions known to be involved in the modulation of
      emotional processes (hippocampus, hypothalamus and striatum). Finally, the third
      objective was to examine the effects of anxiolytic drug treatments on the
      anxiogenic responses elicited by a cat odor (i.e. a feces) in Swiss mice
      previously exposed to a cat using the free-exploration test. Results from the
      strain comparison showed that mice could be divided into three distinct groups:
      two non-reactive strains (NZB and SJL) which were relatively insensitive to
      predatory exposure and/or odor; five intermediate-reactive strains (Swiss, NMRI,
      CBA, C3H and BALB/c) which displayed clear anxiogenic-like responses only when
      exposed to both cat and, subsequently, to feces; and two high reactive strains
      (C57BL/6 and DBA/2) which showed anxiogenic-like reactions following cat
      exposure, regardless of the stimulus (clay or feces) present in the free
      exploration cage. Neurochemical data revealed that, while brain levels of NA, DA,
      5-HT in cat exposed Swiss mice were not significantly different from those of
      control animals, turnover rates of these monoamines were increased in the
      hippocampus (NA and 5-HT), hypothalamus and striatum (DA) after cat exposure.
      Results from pharmacological experiments indicated that repeated administration
      of the 5-HT reuptake inhibitor fluoxetine (5-20 mg/kg, twice a day, for 5 days)
      completely abolished avoidance of the cat feces in Swiss mice previously exposed
      to the predator. Neither acute nor repeated administration of the classical
      anxiolytic diazepam was able to reduce avoidance behavior of the anxiogenic
      stimulus in the free-exploration test. Taken together, these findings indicate
      that the exposure of mice to unavoidable predatory stimuli is associated with
      behavioral and neurochemical changes consistent with increased anxiety.

PMID- 11522333
TI  - Inhibition of the glutamate transporter by L-trans-PDC in the nucleus accumbens
      prevents the locomotor response to amphetamine.
AB  - Infusion in the nucleus accumbens of the glutamate uptake inhibitor L-trans-PDC
      prevented the amphetamine-induced locomotor response. Since L-trans-PDC has been
      shown to block the amphetamine-induced increase in glutamate but not in DA
      release, our result indicates that the glutamate transporter is an obligatory
      target for the activating properties of amphetamine.

PMID- 11522334
TI  - A comparison of membrane vs. intracellular estrogen receptor-alpha in GH(3)/B6
      pituitary tumor cells using a quantitative plate immunoassay.
AB  - The plasma membrane form of the estrogen receptor-alpha (mER-alpha) is involved
      in rapid estrogen-induced prolactin release from GH(3)/B6 rat pituitary tumor
      cells and can be detected immunocytochemically using several estrogen receptor
      alpha (ER-alpha) antibodies. We recently described staining of fixed cells via a
      biotin-avidin-alkaline phosphatase sandwich assay. From this protocol, we have
      developed a rapid, quantifiable 96-well plate immunoassay for mER-alpha, using a
      different alkaline phosphatase substrate, para-nitrophenylphosphate, which
      generates a soluble yellow product, para-nitrophenol. We also permeabilized cells
      with detergent during fixation to measure intracellular ER-alpha (iER-alpha) with
      the same assay and then compared intracellular versus membrane ER-alpha levels in
      two GH(3)/B6 cell subclones originally selected for high and absent mER-alpha
      expression by immunocytochemistry. While the F10 subclone expresses plentiful
      amounts of the mER-alpha, the D9 subclone has undetectable levels of mER-alpha
      using this assay. In addition, there is a seven-fold difference in iER-alpha
      expression between the high (F10) and no (D9) mER-alpha expressing subclones. In
      the high mER-alpha expressing cell line, the mER-alpha totals approximately one
      third of total cellular ER-alpha. Neither membrane or intracellular forms of ER
      beta were detected with this assay. The pNp assay allows convenient and
      quantitative comparison of multiple parameters of mER-alpha and iER-alpha
      regulation and should be applicable to other antigens that are expressed on the
      cell surface as well as intracellularly.

PMID- 11522335
TI  - Stability of salivary steroids: the influences of storage, food and dental care.
AB  - We studied influences of dental care, food and storage on the reproducibility of
      salivary steroid levels. Cortisol (F), 17OH-progesterone (17OHP) and Progesterone
      (P) were measured using adapted commercial radioimmunoassays. Saliva samples of
      healthy adults (n = 15; m:8; f:7) were collected directly before and after dental
      care, and directly before and after breakfast with various foodstuffs. A second
      experiment investigated stability of steroids under different storage conditions.
      Four series of identical saliva portions (I: Native saliva; II: Centrifuged
      saliva; III: Saliva with trifluor acetate (TFA); IV: Saliva with 0.5% NaN(3))
      were stored at room temperature and at 4 degrees C for up to three weeks. To
      demonstrate influences of repeated thawing and re-freezing of saliva on steroid
      values, saliva samples (n = 15) were divided into identical portions. These
      portions were frozen and re-thawed up to 5 times before measurement. Neither
      dental care nor intake of bread or milk effected the reproducibility of F, 170HP,
      and P. Steroid levels decreased significantly in the course of three weeks under
      different storage conditions (P < 0.001). This decrease was clinically relevant
      from the second week onward, with exception of NaN(3) treated samples. After
      repeated freezing and re-thawing 17OHP and P decreased slightly (about 5%). Only
      F decreased significantly after the third thawing (P < 0.001). The results show
      the usefulness of standardized handling of saliva samples for improving
      reproducibility and reliability of salivary steroid measurements.

PMID- 11522336
TI  - Production of 16beta-(acetoxy)acetoxy derivatives by reaction of 17-keto steroid
      enol acetates with lead (IV) acetate.
AB  - Treatment of enol acetates of 3beta-acetoxyandrost-5-en-17-one and its 5alpha
      reduced analog, 5alpha-androstan-17-one, and estrone acetate, 1-4, with
      Pb(OCOCH(3))(4) in acetic acid and acetic anhydride gave the previously
      unreported products, 16beta-(acetoxy)acetoxy-17-ketones 8-10 and 12, in 9-15%
      yields along with the known major products, 16beta-acetoxy-17-ketones 5-7 and 11.
      Similar treatment of the 16beta-acetoxy-17-ketones with the lead reagent did not
      yield the corresponding (acetoxy)acetates. Reaction of the enol acetate 3 with
      Pb(OCOCD(3))(4) in CD(3)COOD yielded principally the labeled (acetoxy)acetate 10
      d(3), which had a CD(3)COOCH(2)COO moiety at C-16beta. In contrast, when the
      deuterated enol acetate 3-d(3), which was obtained by treatment of the 17-ketone
      14 with (CD(3)CO)(2)O in the presence of LDA and which had a CD(3)COO moiety at C
      17, was reacted with Pb(OCOCH(3))(4), the resulting product was the labeled
      compound 10-d(2). This product had a CH(3)COOCD(2)COO function at C-16beta. Based
      on these results, along with further isotope-labeling experiments, it seems
      likely that the (acetoxy)acetate is produced through a lead (IV) acetate
      catalyzed migration of the 17-acetyl function of the enol acetate to the C-16beta
      position followed by attack of an acetoxy anion of the lead reagent.

PMID- 11522337
TI  - Aromatase in synovial cells from postmenopausal women.
AB  - Peripheral aromatization of androgens exerts estrogenic actions in many tissues.
      In this study, osteoarthritis synoviocytes were examined to clarify the possible
      action of adrenal androgen on synovial cell. Synoviocytes from postmenopausal
      women are able to express aromatase mRNA. By sequence analysis, the PCR fragment
      (485 bp) was determined to be 100% identical to that of human placental aromatase
      cDNA. Moreover, this study demonstrates that adrenal androgen, androstenedione,
      is converted to estrone (E(1)) and estradiol (E(2)) in synoviocytes by aromatase
      which is positively regulated by glucocorticoids such as dexamethasone. E(2)
      production reduced significantly IL-6 secretion. These data provide preliminary
      evidence that in situ estrogen production by synoviocytes may have a role in OA
      susceptibility. However the role of E(2) in OA is not clear and remains to be
      determined.

PMID- 11522338
TI  - Determination of 17alpha-hydroxypregnenolone in human plasma by routine isotope
      dilution mass spectrometry using benchtop gas chromatography-mass selective
      detection.
AB  - A first assay based on stable isotope dilution/gas chromatography-mass
      spectrometry has been developed for plasma 17alpha-hydroxypregnenolone, the
      leading marker of 3beta-hydroxysteroid dehydrogenase deficiency. Equilibration of
      plasma with internal standard was followed by solid phase extraction. After clean
      up using Sephadex LH-20 mini columns, heptafluorobutyrates were prepared as
      derivatives. Quantification was achieved by selected ion monitoring of m/z 467.0
      (analyte) and m/z 471.0 (internal standard). 0.030 pmol of 17alpha
      hydroxypregnenolone gave a signal to noise ratio of 3.7. Calibration plot was
      linear. Spiking experiments showed good accuracy with relative errors < 3.7%.
      Intraassay precision CV was 8.3% and interassay precision CV was 5.6%. Requiring
      small amounts of plasma, the rapid, convenient work up and the application of
      bench top GC/MS instrumentation proved our method suitable for routine clinical
      use in adults and children.

PMID- 11522339
TI  - Inhibition of human cytochrome P450 aromatase activity by butyltins.
AB  - Organotin compounds are widely used as antifouling agents and bioaccumulate in
      the food chain. Tributyltin chloride (TBT) has been shown to induce imposex in
      female gastropods. On the basis of this observation it has been suggested that
      TBT acts as an endocrine disrupter inhibiting the conversion of androgens to
      estrogens mediated by the aromatase cytochrome P450 enzyme. However, to date, the
      molecular basis of TBT-induced imposex and in particular its putative inhibitory
      effects on human aromatase cytochrome P450 activity have not been investigated.
      Therefore, we examined the effects of the organotin compounds tetrabutyltin
      (TTBT), TBT, dibutyltin dichloride (DBT) and monobutyltin trichloride (MBT) on
      human placental aromatase activity. TBT was found to be a partial competitive
      inhibitor of aromatase activity with an IC(50) value of 6.2 microM with 0.1
      microM androstenedione as substrate. TBT impaired the affinity of the aromatase
      to androstenedione but did not affect electron transfer from NADPH to aromatase
      via inhibiting the NADPH reductase. DBT acted as a partial but less potent
      inhibitor of human aromatase activity (65% residual activity), whereas TTBT and
      MBT had no effect. The residual activity of TBT-saturated aromatase was 37%. In
      contrast, human 3beta-HSD type I activity was only moderately inhibited by TBT
      (80% residual activity). Moreover, neither TTBT or DBT nor MBT inhibited the
      3beta-HSD type I activity. Together, these results suggest that the environmental
      pollutants TBT and DBT, both present in marine organisms, textile and plastic
      products, may have specific impacts on the metabolism of sex hormones in humans.

PMID- 11522340
TI  - A novel sterol from Chinese truffles Tuber indicum.
AB  - From the fruiting bodies of Ascomycetes Tuber indicum, a new steroidal glucoside
      with polyhydroxy ergosterol nucleus, tuberoside (2), has been isolated along with
      additional four known ergosterol derivatives, (22E, 24R)-ergosta-7, 22-dien
      3beta, 5alpha, 6beta-triol (1), 5alpha, 8alpha-epidioxy-(22E, 24R)-ergosta-6, 22
      dien-3beta-ol (3), (22E, 24R)-ergosta-5, 22-dien-3beta-ol (4), and (22E, 24R)
      ergosta-4, 6, 8(14), 22-tetraen-3-one (5). The structure of new compound was
      established as 3-O-beta-D-glucopyranosyl-(22E, 24R)-ergosta-7, 22-dien-5alpha,
      6beta-diol (2) on the basis of chemical and spectroscopic means ((1)H NMR, (13)C
      NMR, HMQC, HMBC, MS, and IR). This is the first example of isolation of a
      polyhydroxylated ergosterol glucoside from higher fungi in nature.

PMID- 11522341
TI  - alpha,beta-Dibenzyl-gamma-butyrolactone lignan alcohols: total synthesis of (+/-)
      7'-hydroxyenterolactone, (+/-)-7'-hydroxymatairesinol and (+/-)-8
      hydroxyenterolactone.
AB  - Two trans-alpha,beta-dibenzyl-gamma-butyrolactone lignans carrying a hydroxyl
      group at the beta-benzylic carbon atom and a alpha-hydroxy alpha,beta-dibenzyl
      gamma-butyrolactone lignan were synthesized in racemic form using the tandem
      conjugate addition reaction to construct the basic lignan skeleton. Subsequent
      reaction steps involved either a catalytic reduction of the regenerated keto
      group to the alcohol, or a hydrogenolysis to benzylic methylene followed by
      lactone enolate formation and oxidation to give the alpha-hydroxybutyrolactones.
      These procedures were applied for the synthesis of 7'-hydroxyenterolactones and
      7'-hydroxymatairesinols, and 8-hydroxyenterolactones, respectively. The
      diastereomeric mixtures of these compounds were separated either by HPLC
      techniques or column chromatography and the structures were elucidated using NMR
      spectroscopy.

PMID- 11522342
TI  - Synthesis and biological evaluation of novel daunorubicin-estrogen conjugates.
AB  - The synthesis of two novel daunorubicin-estrogen conjugates with a steroidal and
      a non-steroidal ligand was undertaken in an attempt to target the cytotoxicity of
      anthracycline to estrogen-receptor positive cells. These conjugates (3 and 4), in
      contrast to their corresponding ligands, displayed weak binding affinities of
      0.079 and 0.851 for the estrogen receptor. Conjugate 3 was consistently more
      cytotoxic than 4, which however showed some selectivity to estrogen receptor
      positive cell lines.

PMID- 11522344
TI  - Characterization of two cysteine proteinases secreted by Fasciola hepatica and
      demonstration of their kininogenase activity.
AB  - We have isolated and purified two cysteine proteinases of molecular weights 25
      and 26 kDa, secreted by Fasciola hepatica adult worm. Their 15 N-terminal
      residues were found to be identical to those of earlier described cathepsin L
      like enzymes, isolated from the same source, reported as CL1 and CL2.
      Radioimmunoassay experiments have shown that these CL1- (25 kDa) and CL2-like (26
      kDa) cysteine proteinases mediated kinin release from high molecular weight
      kininogen (HMWK). Lys-bradykinin (KRPPGFSPFR) was characterized as the kinin
      released from a synthetic fragment of HMWK from Leu373 to Ile393 (Abz
      LGMISLMKRPPGFSPFRSSRI-NH2) labeled with the fluorescent group Abz (ortho
      aminobenzoic acid). We examined the activity of CL1- and CL2-like on internally
      quenched fluorescent peptides containing HMWK sequences, in which Met379-Lys380
      or Arg389-Ser390 bonds were present in the middle of the molecules. These
      peptides were flanked by the fluorescent donor-acceptor pair Abz and EDDnp (N
      [2,4-dinitrophenyl] ethylenediamine). Peptidyl-methylcoumarin amides (MCA) were
      used to study the substrate specificity requirements. The enzymes presented
      significantly lower Km values at pH 8.0. The inverse was observed with the kcat
      values, which were higher at pH 5.0.

PMID- 11522345
TI  - Characterization of P-type ATPase 3 in Plasmodium falciparum.
AB  - We report the nucleotide sequence, derived amino acid sequence and expression
      profile of P-type ATPase 3 (PfATPase3) from Plasmodium falciparum. An open
      reading frame of 7362 nucleotides, interrupted by a single intron of 168 nt,
      encoded a protein product of 2394 amino acids with a predicted MW of 282791 Da.
      Hydropathy analysis of PfATPase3 revealed six amino-terminal and six carboxyl
      terminal membrane spanning regions (M1-12) flanking a large hydrophilic domain
      with a smaller hydrophilic loop between M4 and M5. Based on a phylogenetic
      comparison of conserved domains present in P-type ATPases from other organisms,
      PfATPase3 resembled a Type-V ATPase for which the transport affinity is unknown.
      The PfATPase3 topology was interrupted by four regions, termed 'inserts', unique
      to malarial P-type ATPases, which were high in asparagine residues and charged
      amino acids (inserts I1-I4). Inserts I1 and I3 also contained repeated amino acid
      motifs. The number and composition of repeated amino acid motifs in insert I3
      were variable in seven P. falciparum strains tested. PfATPase3 was 80.2% similar
      to the non-insert portions of P. yoelii ATPase3, although their inserts differed
      in length and composition. PfATPase3 mRNA was most abundant relative to beta
      tubulin during the latter half of the erythrocytic cycle and was also present in
      gametocytes. Using affinity-purified antibody to a 14 amino acid PfATPase3
      epitope, a 260 kDa protein was detected by Western analysis. Based on
      immunofluorescence, the PfATPase3 protein was located intracellularly in
      gametocytes and, to a lesser extent, in late erythrocytic stages.

PMID- 11522346
TI  - Two glycoforms are present in the GPI-membrane anchor of the surface antigen 1
      (P30) of Toxoplasma gondii.
AB  - SAG1 (P30) is the major surface protein of the Toxoplasma gondii tachyzoite, the
      life cycle stage associated with the acute phase of infection. The protein is
      inserted into the parasite's plasma membrane by a glycosyl-phosphatidylinositol
      anchor, a modification that is present on all T. gondii surface proteins
      characterized so far. Here we describe a detailed structural analysis of this
      anchor. GPI anchor peptides were isolated from [3H]glucosamine labeled purified
      P30 by protease digestion and phase partitioning. Neutral glycans were prepared
      from this material by dephosphorylation and deamination. Two glycoforms were
      characterized by gel filtration and high performance ion exchange chromatography
      in combination with exoglycosidase treatment. Both forms were shown to carry an N
      acetylgalactosamine bound to the first mannose of the conserved three-mannosyl
      core. Glycan B carries an additional terminal hexose linked to GalNAc. To
      identify the nature of this hexose, bulk anchor peptide was prepared and glycans
      were purified by aminopropyl-HPLC. Highly purified glycans were subjected to
      MALDI-TOF-MS and, after derivatization, to FAB-MS and methylation linkage
      analysis. The structures of the two anchors found on SAG1 were determined to be:
      Man-alpha1,2-Man-alpha1,6-Man-[GalNAc-beta1,4-]-alpha1,4-GlcN-PI and Man-alpha1,2
      Man-alpha1,6-Man [Glc-alpha1,4-GalNAc-beta1,4-]-alpha1,4-GlcN-PI. Comparison of
      these structures with free GPI glycolipid precursors characterized in T. gondii
      suggests that core modification of the anchor takes place prior to transfer to
      the protein.

PMID- 11522347
TI  - A protease inhibitor associated with the surface of Toxoplasma gondii.
AB  - Toxoplasma gondii has a broad host-range including man and a variety of warm
      blooded animals. The ability to infect and survive in this wide spectrum of hosts
      suggests highly evolved mechanisms to handle the harsh environments encountered.
      Here we show that extracellular tachyzoites are resistant to milligram levels of
      trypsin and describe the presence of an inhibitor of trypsin associated with the
      surface of T. gondii, TgTI. TgTI has an estimated molecular mass of 37000 dalton
      and is encoded by the TgTI-gene which is found at low abundance as an expressed
      sequence tag (EST) in both the bradyzoite and tachyzoite stages. The inhibitory
      binding region was found to be in the N-terminus of TgTI where aminoacid
      alignment to earlier described protease inhibitors demonstrates 75% similarity.
      In functional analysis, recombinant TgTI-protein inhibits the activity of trypsin
      approximately 10 times more efficiently than an inhibitor isolated from soybean.
      In contrast to other known trypsin inhibitors, TgTI also possesses a predicted
      membrane-binding region. Polyclonal antibodies raised against recombinant TgTI
      bind to the surface of the tachyzoite stage as seen both by immunofluorescence
      and immunoprecipitation of surface labelled parasite proteins. The high survival
      rate of the parasite in the upper gastrointestinal tract may be enhanced by the
      presence of the TgTI-molecule.

PMID- 11522348
TI  - Genomic organization and functional characterization of the Leishmania major
      Friedlin ribosomal RNA gene locus.
AB  - The sequence and gene organization of the ribosomal RNA (rRNA) genes of
      Leishmania major Friedlin (LmjF) were determined. Interestingly, the rDNA repeat
      unit contained a duplicated 526 bp fragment at the 3' end of the unit with two
      copies of the LSUepsilon rRNA gene. Our results suggested the presence of only
      approximately 24 copies of the rRNA unit per diploid genome in LmjF. Repetitive
      elements (IGSRE) of 63 bp occurred in the intergenic spacer (IGS) between the
      LSUepsilon and the SSU rRNA genes. Among the different rDNA units, the region
      containing the IGSRE fluctuated in length from approximately 1.3 to approximately
      18 kb. The transcription initiation site (TIS) of the rRNA unit was localized by
      primer extension to 1043 bp upstream of the SSU gene and 184 bp downstream of the
      IGSRE. Sequence comparison among several species of Leishmania showed a high
      degree of conservation around the TIS. Moreover, the IGSRE also showed
      considerable similarity between Leishmania species. In transient transfection
      assays, a fragment containing the TIS directed a 164- to 178-fold increase in
      luciferase activity over the no-insert control, indicating the presence of a
      promoter within this 391 bp fragment. The LmjF promoter region was also
      functional in other species of Leishmania. Nuclear run-on analyses demonstrated
      that only the rRNA-coding strand is transcribed, downstream of this RNA
      polymerase I (pol I) promoter. These experiments also suggested that
      transcription terminates upstream of the IGSRE.

PMID- 11522349
TI  - Cathepsin B-like cysteine proteases and Caenorhabditis elegans homologues
      dominate gene products expressed in adult Haemonchus contortus intestine.
AB  - Proteins expressed by nematode intestinal cells are potential targets for
      parasite control by immune or chemical based strategies. To expand our knowledge
      on nematode intestinal proteins, expressed sequence tags were generated for 131
      cDNA clones from the intestine of adult female Haemonchus contortus. An estimated
      55 distinct protein genes or gene families were identified. Predicted proteins
      represented diverse functions. Several predicted polypeptides were related to H.
      contortus proteins implicated in inducing protective immunity against challenge
      infections of this parasite. The dominant intestinal transcripts were represented
      by cathepsin B-like cysteine protease genes (cbl) (17% of protein coding
      expressed sequence tags (ESTs) analyzed). An estimated 11 previously undescribed
      cbl genes were identified, doubling the recognized members of this gene family.
      Multiple C-type lectin sequences were identified. Other notable sequences
      included a predicted Y-box binding protein, serine/threonine kinases and a cyclin
      E-like sequence. Predicted protein homologues were found in Caenorhabditis
      elegans for all but one H. contortus sequence (99%), while fewer homologues from
      other parasitic nematodes were found. Many of the proteases, lipase and C-type
      lectin homologues in C. elegans had apparent signal peptides, suggesting that
      they are secreted. Several gene products had no obvious similarity outside the
      phylum Nematoda. The ESTs identified intestinal genes with potential application
      to immune control, understanding of basic intestinal regulatory processes and
      refinement of nematode genomic resources.

PMID- 11522350
TI  - Molecular characterisation of mitochondrial and cytosolic trypanothione-dependent
      tryparedoxin peroxidases in Trypanosoma brucei.
AB  - In trypanosomatids, removal of hydrogen peroxide and other aryl and alkyl
      peroxides is achieved by the NADPH-dependent trypanothione peroxidase system,
      whose components are trypanothione reductase (TRYR), trypanothione, tryparedoxin
      (TRYX) and tryparedoxin peroxidase (TRYP). Here, we report the cloning of a multi
      copy tryparedoxin peroxidase gene (TRYP1) from Trypanosoma brucei brucei encoding
      a protein with two catalytic VCP motifs similar to the cytosolic TRYP from
      Crithidia fasciculata. In addition, we characterise a novel single copy gene
      encoding a second tryparedoxin peroxidase (TRYP2). TRYP2 shows 51% similarity to
      TRYP1, possesses a putative mitochondrial import sequence at its N-terminus and
      has a variant IPC motif replacing the second VCP motif implicated in catalysis in
      other 2-Cys peroxiredoxins. TRYP1 and TRYP2 were expressed in Escherichia coli,
      and the purified recombinant proteins shown to utilise hydrogen peroxide in the
      presence of NADPH, trypanothione, TRYR and TRYX from T. brucei, similar to the C.
      fasciculata cytoplasmic system. Western blots showed that TRYX, TRYP1 and TRYP2
      are expressed in both bloodstream and procyclic forms of the life cycle. To
      determine the precise localisation of TRYX, TRYP1 and TRYP2 in the parasite,
      polyclonal antibodies to purified recombinant TRYX and TRYP1 and monoclonal
      antibody to TRYP2 were generated in mice. In-situ immunofluorescence and
      immunoelectron microscopy revealed a colocalisation of TRYX and TRYP1 in the
      cytosol, whereas TRYP2 was principally localised in the mitochondrion.

PMID- 11522351
TI  - Characterization and expression of enzymatically active recombinant filarial
      prolyl 4-hydroxylase.
AB  - The cuticle of parasitic nematodes consists primarily of a network of collagen
      molecules. The enzyme responsible for collagen maturation is prolyl 4
      hydroxylase, making this enzyme a central activity in cuticle biosynthesis and a
      potentially important chemotherapeutic target. Adult and embryonic Brugia malayi
      are shown to be susceptible to inhibitors of vertebrate prolyl 4-hydroxylase,
      with exposed parasites exhibiting pathologies consistent with a disruption in
      cuticle biosynthesis. A full-length cDNA (Ov-phy-1) encoding a catalytically
      active alpha-subunit of Onchocerca volvulus prolyl 4-hydroxylase was isolated and
      characterized. The derived amino acid sequence of Ov-phy-1 encoded a peptide that
      was most similar to the two Caenorhabditis elegans prolyl 4-hydroxylase
      homologues and to the isoform II enzymes of vertebrates. Expressed sequence tag
      (EST) analysis and developmental polymerase chain reaction (PCR) studies
      demonstrated that Ov-phy-1 was expressed in L3 and adult parasites. The gene
      encoding the Ov-phy-1 open reading frame contained 11 introns, similar in
      structure to the gene encoding human prolyl 4-hydroxylase isoform I. Genomic
      Southern blot, EST and genomic PCR studies demonstrated that the O. volvulus
      genome contained between three and eight genes closely related to Ov-phy-1. Co
      expression of Ov-phy-1 with the O. volvulus homologue of protein disulfide
      isomerase in a baculovirus system resulted in the production of enzymatically
      active O. volvulus prolyl 4-hydroxylase. In vitro production of enzymatically
      active O. volvulus prolyl 4-hydroxylase should facilitate identification of
      specific inhibitors of the parasite enzyme.

PMID- 11522352
TI  - FMRFamide-related peptides in potato cyst nematodes.
AB  - This study presents data demonstrating the presence of FMRFamide-related peptides
      (FaRPs) in potato cyst nematodes (PCN). Five transcripts of FaRP encoding genes,
      designated gpflp-1 to gpflp-5, were characterised using RACE. In terms of ORFs,
      gpflp-1 was 444 base pairs (bp) long and coded for four copies of the FaRP, PF3
      (KSAYMRFamide) whilst gpflp-2 was 309 bp long and encoded one copy of the
      peptide, KNKFEFIRFamide. gpflp-3 (420 bp) Encoded two copies of KHEYLRFamide
      (AF2) and the genes gpflp-4 and gpflp-5 encoded a total of 11 FaRPs, most of
      which are novel to PCN. FMRFamide-related peptide (FaRP)-like immunoreactivity
      was observed in both PCN species, Globodera pallida and Globodera rostochiensis,
      using an antiserum raised against the invertebrate peptide, FMRFamide.
      Immunopositive neurones were found throughout the central nervous system in the
      ventral and dorsal nerve cords and the circumpharyngeal and perianal nerve rings.
      Reactive neurones were also present peripherally, innervating the highly muscular
      pharynx with a nerve net and ring-like structures. Positive immunostaining was
      also observed in neurones running toward the stylet protractor muscles and/or the
      anterior sensory apparatus. This study implicates a role for FaRPs in feeding,
      host penetration and sensory function of PCN. This is the first study to
      characterise FaRP encoding genes from a plant-parasitic nematode using a targeted
      PCR based RACE approach and further underlines the importance and diversity of
      this neuropeptide group in the phylum Nematoda.

PMID- 11522353
TI  - A Schistosoma mansoni Pad1 homologue stabilizes c-Jun.
AB  - We report the cloning and functional analysis of a Pad1 homologue (SmPOH) from
      Schistosoma mansoni. SmPOH encodes a protein of approximately 35 kDa with high
      amino acid identities to yeast Pad1 (65%) and its human homologue, POH1 (78%).
      Members of the Pad1 family are subunits of the 26S proteasome and have been
      implicated as positive modulators of transcription in yeast. Recombinant SmPOH
      expressed in COS7 cells exhibited a punctate pattern of distribution throughout
      the cytoplasm and nucleus, predominantly in the nuclear periphery, a distribution
      consistent with that of the cellular proteasome. Transient overexpression of
      SmPOH in COS7 cells caused a dose-dependent stimulation in AP-1 transcriptional
      activity, as determined by a reporter gene assay. This effect was associated with
      a pronounced increase in the levels of cellular c-Jun. In vitro degradation
      assays further demonstrated that SmPOH specifically decreased the rate of c-Jun
      degradation in a dose dependent manner. Taken together, these results suggest
      that SmPOH, and possibly other related Pad1 proteins, function as positive
      modulators of transcription by increasing the stability of cellular c-Jun, making
      elevated amounts of this protein available for transactivation of AP-1-responsive
      genes.

PMID- 11522354
TI  - Identification and characterization of genes encoding novel Rab proteins from
      Entamoeba histolytica.

PMID- 11522355
TI  - Characterization of the Ehrab8 gene, a marker of the late stages of the secretory
      pathway of Entamoeba histolytica.

PMID- 11522356
TI  - cAMP-specific phosphodiesterase TbPDE1 is not essential in Trypanosoma brucei in
      culture or during midgut infection of tsetse flies.

PMID- 11522357
TI  - Echinococcus granulosus antigen B is encoded by a gene family.

PMID- 11522358
TI  - Targeted disruption of an essential RNA-binding protein perturbs cell division in
      Trypanosoma brucei.

PMID- 11522359
TI  - Lack of expression of the dense granule protein GRA5 does not affect the
      development of Toxoplasma tachyzoites.

PMID- 11522360
TI  - The bacterial ParA-ParB partitioning proteins.
AB  - A pair of genes designated parA and parB are encoded by many low copy number
      plasmids and bacterial chromosomes. They work with one or more cis-acting sites
      termed centromere-like sequences to ensure better than random predivisional
      partitioning of the DNA molecule that encodes them. The centromere-like sequences
      nucleate binding of ParB and titrate sufficient protein to create foci, which are
      easily visible by immuno-fluorescence microscopy. These foci normally follow the
      plasmid or the chromosomal replication oriC complexes. ParA is a membrane
      associated ATPase that is essential for this symmetric movement of the ParB foci.
      In Bacillus subtilis ParA oscillates from end to end of the cell as does MinD of
      E. coli, a relative of the ParA family. ParA may facilitate ParB movement along
      the inner surface of the cytoplasmic membrane to encounter and become tethered to
      the next replication zone. The ATP-bound form of ParA appears to adopt the
      conformation needed to drive partition. Hydrolysis to create ParA-ADP or free
      ParA appears to favour a form that is not located at the pole and binds to DNA
      rather than the partition complex. Definition of the protein domains needed for
      interaction with membranes and the conformational changes that occur on
      interaction with ATP/ADP will provide insights into the partitioning mechanism
      and possible targets for inhibitors of partitioning.

PMID- 11522361
TI  - Parallel cascade identification and its application to protein family prediction.
AB  - Parallel cascade identification is a method for modeling dynamic systems with
      possibly high order nonlinearities and lengthy memory, given only input/output
      data for the system gathered in an experiment. While the method was originally
      proposed for nonlinear system identification, two recent papers have illustrated
      its utility for protein family prediction. One strength of this approach is the
      capability of training effective parallel cascade classifiers from very little
      training data. Indeed, when the amount of training exemplars is limited, and when
      distinctions between a small number of categories suffice, parallel cascade
      identification can outperform some state-of-the-art techniques. Moreover, the
      unusual approach taken by this method enables it to be effectively combined with
      other techniques to significantly improve accuracy. In this paper, parallel
      cascade identification is first reviewed, and its use in a variety of different
      fields is surveyed. Then protein family prediction via this method is considered
      in detail, and some particularly useful applications are pointed out.

PMID- 11522362
TI  - Molecular and enzymatic characterization of a levan fructotransferase from
      Microbacterium sp. AL-210.
AB  - Microbacterium sp. AL-210 producing a novel levan fructotransferase (LFTase) was
      screened from soil samples. The LFTase was purified to homogeneity by (NH4)2SO4
      fractionation, column chromatography on Resource Q, and Superdex 200HR. The
      molecular weight of the purified enzyme was estimated to be approximately 46 kDa
      by both SDS-PAGE and gel filtration, and the enzyme's isoelectric point was pH
      4.8. The major product produced from the levan hydrolysis by the enzyme reaction
      was identified by atmospheric pressure ionization mass spectrometry and NMR
      analysis as di-D-fructose-2,6':6,2'-dianhydride (DFA IV). The optimum pH and
      temperature for DFA IV production were 7.0 and 40 degrees C, respectively. The
      enzyme was stable at a pH range 7.0-8.0 and up to 40 degrees C. The enzyme
      activity was inhibited by FeCl2 and AgNO3. The enzyme converted the levan to DFA
      IV, with a conversion yield of approximately 44%. A gene encoding the LFTase
      (lftM) from Microbacterium sp. AL-210 was cloned and sequenced. The nucleotide
      sequence included an ORF of 1593 nucleotides, which is translated into a protein
      of 530 amino acid residues. The predicted amino acid sequence of the enzyme
      shared 79% of the identity and 86% of the homology with that of Arthrobacter
      nicotinovorans GS-9.

PMID- 11522363
TI  - Scale-up of a myoblast culture process.
AB  - The effects of different types of cell carriers, strategies for cell transfer on
      carriers, and of several fusion inhibitors on the growth kinetics of primary
      human myoblasts culture were studied in order to develop a bioprocess suitable
      for the treatment of Duchenne muscular dystrophy based on the transplantation of
      unfused cells. Our results indicate that myoblast production is larger on Cytodex
      1 and 3 than on polypropylene or polyester fabrics and on a commercial porous
      macrocarrier. Myoblast growth conditions with Cytodex 1 were further investigated
      to establish the bioprocess operating conditions. It was found that microcarrier
      density of 3 g DW l(-1), inoculum density of 2x10(5) cells ml(-1), and continuous
      agitation speed of 30-rpm result in final myoblast production comparable to
      static cultures. However, for all the culture conditions used, myoblasts growth
      kinetics exhibited a lag phase that lasted a minimum of 1 week prior to growth,
      the end of the lag phase correlating with the appearance of microcarrier
      aggregates. Based on this observation, we propose that aggregation promotes cell
      growth by offering a network of very large inter-particular pores that protect
      cells from mechanical stress. We took advantage of the presence of these
      aggregates for the scale-up of the culture process. Indeed, using myoblast-loaded
      microcarrier-aggregates instead of myoblast suspension to inoculate a fresh
      suspension of microcarriers significantly reduced the duration of the lag phase
      and allowed the scale-up of the bioprocess at the 500-ml scale. In order to
      ensure the production of unfused myoblasts, the efficiency of five different
      fusion inhibitors was investigated. Only calpeptin (9.1 microg ml(-1))
      significantly inhibited the fusion of the myoblasts, while TGFbeta (50 ng ml(-1))
      and LPA (10 microg ml(-1)) increased myoblasts growth but did not affect fusion,
      sphingosine (30 microg ml(-1)) induced a 50% death and NMMA (25 microg ml(-1))
      had no effect on either growth or fusion. Finally, transplantation trials on
      severe combined immunodeficient mice showed that microcarrier-cultured human
      myoblasts grown using the optimized bioprocess resulted in grafts as successful
      as myoblasts grown in static cultures. The bioprocess, therefore, prove to be
      suitable for the large-scale production of myoblasts required for muscular
      dystrophy treatment.

PMID- 11522364
TI  - Docosahexaenoic acid ethyl esters from Isochrysis galbana.
AB  - In order to produce docosahexaenoic acid (DHA), a culture of the microalgal
      strain Isochrysis galbana was implemented. In Erlenmeyer flasks, a natural
      seawater medium, the Provasoli 1/3 medium, was compared to the classical Jones
      medium for DHA production. The Provasoli 1/3 medium stimulated growth (0.44 d(
      1)), but influenced DHA accumulation negatively (0.240 pg cell(-1)). However, DHA
      production per liter of culture medium were of the same order of magnitude with
      both media (0.961 mg l(-1)). In a 2-l bioreactor, DHA production per liter of
      culture medium did not increase significantly between 4 and 8 days of culture.
      With a view to optimize DHA productivity, cells should be harvested at the end of
      exponential phase i.e. after 4 days of culture. Two strategies were then
      attempted to produce DHA ethyl esters. First, lipids from I. galbana were
      submitted to lipase-catalyzed transesterification with ethanol. Secondly, fatty
      acids from I. galbana were submitted to lipase catalyzed esterification with
      ethanol. In both cases, lipase from Candida antarctica was shown to be the best
      candidate, among the five tested, with conversion yields of 20 and 60% after 24 h
      of transesterification and esterification respectively.

PMID- 11522365
TI  - Cultivation of Polyporus squamosus for pectinase production in aqueous two-phase
      system containing sugar beet extraction waste.
AB  - Cultivation of the fungus Polyporus squamosus for pectinase production was
      studied in a polyethylene glycol/crude dextran aqueous two-phase system, with
      sugar beet extraction waste as pectin source. Fungal growth was restricted to the
      bottom phase and the amounts of biomass and exo-pectinase activity produced were
      superior to in homogeneous cultivation. The partition coefficients of endo
      pectinase and exo-pectinase were 4.26 and 2.78, respectively. The top phase
      yields in the single extraction step were about 90% for both pectinases.

PMID- 11522366
TI  - Effect of oleoresin capsicum (OC) and ortho-chlorobenzylidene malononitrile (CS)
      on ciliary beat frequency.
AB  - Tear gases are largely used to control civil unrest. Their incapacitating effects
      involve the eyes, skin, and respiratory tract. We aimed to evaluate the effects
      of ortho-chlorobenzylidene malononitrile (CS) and oleoresin capsicum (OC) on
      ciliary beat frequency (CBF) of mouse tracheal rings. Addition of 0.05% OC or
      0.01% CS induced a progressive decrease in CBF, from 11.5+/-0.5 to 4+/-0.1 Hz
      (P<0.05) and from 12.5+/-0.5 to 2.5+/-0.1 Hz (P<0.05), respectively, 30 min after
      exposure to the tear gas. Addition of exogenous ATP inhibited the effect of OC,
      suggesting that ATP could be used to counteract these adverse effects on CBF.
      However, ATP was inefficient against CS. Methylene blue and H7 inhibited the
      effects of OC, whereas indomethacin had no effect. None of these drugs affected
      the inhibitory action of CS. These results suggest that the inhibitory effect of
      OC is mediated through the guanylate cyclase-dependent pathway or protein kinase
      C-dependent phosphorylation. Another mechanism is probably involved in CS-induced
      inhibitory effect. Histological analysis of the trachea revealed an increase in
      mucus secretion after exposure to OC, and cytoplasmic vacuoles in epithelial
      cells after exposure to CS.

PMID- 11522367
TI  - Effect of isoproturon pretreatment on the biochemical toxicodynamics of anilofos
      in male rats.
AB  - Anilofos and isoproturon are important herbicides of organophosphorus and
      substituted phenylurea groups, respectively. Isoproturon is an inducer of hepatic
      drug-metabolizing enzymes. Animals and humans have the potential to be exposed to
      the mixture of these intentionally introduced environmental xenobiotics, but
      toxicological interactions between these herbicides are not known. Effects of
      isoproturon pretreatment (675 mg/kg/day for 3 consecutive days) on the toxic
      actions of anilofos administered orally as a single dose (850 mg/kg) were
      evaluated by determining some biochemical attributes in blood
      (erythrocyte/plasma), brain and liver of rats. Anilofos or isoproturon alone or
      in combination failed to produce any noticeable signs of cholinergic
      hyperactivity and behavioural alterations. Isoproturon did not potentiate the
      anticholinesterase action of anilofos in blood and liver. Inhibition of brain
      acetylcholinesterase was significantly protected. No significant alteration in
      anilofos-mediated production of lipid peroxidation was observed in erythrocyte
      and brain of isoproturon-pretreated rats, but it was significantly increased in
      liver. Anilofos did not affect GSH and GST. The isoproturon-mediated increase in
      GSH levels of brain (threefold) and liver (3.6-fold) was also not affected
      following combined administration. GST activity was increased in liver of rats
      given isoproturon alone (fourfold) or in combination with anilofos (2.8-fold).
      Activities of total ATPase, Mg2+-ATPase and Na+-K+-ATPase were not affected in
      rats given either anilofos alone or herbicides in sequence. With these
      treatments, there were no alterations in the protein content of plasma, brain and
      liver. Overall findings of the study indicate that isoproturon pretreatment does
      not alter the toxicity of anilofos, the GSH-GST metabolic pathway may not have a
      significant implication in the detoxification of anilofos and the production of a
      reactive oxygen species may be a factor in mediating anilofos toxicity.

PMID- 11522368
TI  - Prolonged exposure to one percent carbon monoxide causes a leucoencephalopathy in
      un-anaesthetised sheep.
AB  - A total of 15 Levine-prepared adult un-anaesthetised sheep were exposed to 1%
      carbon monoxide (CO) in air for between 45 and 150 min. This exposure caused a
      reversible increase in blood carboxyhaemoglobin concentration and heart rate, and
      a similarly reversible decrease in electroencephalographic frequency and level of
      consciousness. sheep were either normotensive or slightly hypertensive. Sheep
      brains were subsequently examined for histopathological changes at either 5 or 14
      days post- exposure. No dead neurons or apoptotic cells were seen, but most sheep
      given a prolonged exposure to CO had some axonal damage and associated gliosis.
      This damage was concentrated about necrotic micro-foci in the peri-ventricular
      white matter. These results suggest that a leucoencephalopathy is a primary
      consequence of acute and sub-acute CO toxicity.

PMID- 11522369
TI  - Altered expression of the carboxylesterases ES-4 and ES-10 by peroxisome
      proliferator chemicals.
AB  - The nonspecific carboxylesterases (EC.3.1.1.1) are a large group of enzymes that
      play important roles in the metabolism of foreign xenobiotics and endogenous
      lipids, including activators of the peroxisome proliferator-activated receptor
      alpha, a nuclear receptor that is the central mediator of peroxisome proliferator
      (PP) effects in the rodent liver. A number of reports have demonstrated that PP
      exposure leads to alterations in levels of carboxylesterases in the liver. In
      this study, we determined by Western blot analysis whether exposure to diverse PP
      results in alteration of expression of two highly expressed microsomal
      carboxylesterases. Chronic exposure to the PP WY-14,643 (WY) and gemfibrozil
      (GEM), but not di-n-butyl phthalate (DBP), led to decreases in ES-4 in male rat
      livers. ES-4 was increased in female rat livers treated with GEM. WY exposure led
      to decreases in ES-10 in male and female rat livers. ES-10 was increased in
      female rats treated with DBP. Compared with other end points that are altered
      within days after PP exposure, the downregulation of ES-4 and ES-10 by WY was
      considerably slower, occurring between 1 and 5 weeks of exposure. Decreased
      expression of ES-4 was observed at doses of WY or GEM as low as 10 or 8000 ppm,
      respectively, whereas decreased expression of ES-10 was more resistant to changes
      by any PP occurring only with WY at doses as low as 50 ppm. After chronic
      exposure to WY or diethylhexyl phthalate in wild-type mice, kidney, but not
      liver, expression of ES-4 and ES-10 was downregulated. These decreases in kidney
      ES expression were not observed in PPARalpha-null mice lacking a functional
      PPARalpha gene, demonstrating the importance of this transcription factor in
      these changes. These studies demonstrate that ES protein expression is under
      complex control by PP that is sex- and compound-dependent. These results lend
      support to the hypothesis that PP exposure leads to a reprogramming of expression
      of enzymes important in the metabolism of PPARalpha activators.

PMID- 11522370
TI  - Astroglial reaction during the early phase of acute lead toxicity in the adult
      rat brain.
AB  - The developing nervous system is susceptible to lead (Pb) exposure but less is
      known about the effect of this toxic agent in adult rat brain. Since astrocytes
      serve as a cellular Pb deposition site, it is of importance to investigate the
      response of astroglial cells in the adult rat brain in a model of acute lead
      exposure (25 mg/kg b.w. of lead acetate, i.p. for 3 days). An increased
      immunoreactivity of glial fibrillary acidic protein (GFAP) on Western blots was
      noticeable in fractions of astroglial origin-glial plasmalemmal vesicles (GPV)
      and in homogenates from the hippocampus and cerebral cortex but not in the
      cerebellum. The features of enhanced astrocytic reactivity (i.e. large
      accumulation of mitochondria, activated Golgi apparatus and increment of
      gliofilaments) were observed in electron microscopy studies in the same tissues.
      Total glutathione levels increased both in GPV fractions and in brain homogenates
      in the cerebellum (120% above control) and in hippocampus (30% above control).
      The results of current studies indicate that acute lead exposure is accompanied
      by astrocyte activation connected with the presence of the enhanced expression of
      GFAP. It may indicate lead-induced neuronal injury. At the same time, a regional
      enhancement of detoxicative mechanisms (GSH) was noticed, suggesting activation
      of astrocyte-mediated neuroprotection against toxic Pb action.

PMID- 11522371
TI  - Importance of soluble metals and reactive oxygen species for cytokine release
      induced by mineral particles.
AB  - The mechanisms for particle-induced health effects are not well understood, but
      inflammation seems to be of importance. Previously, we have shown that stone
      quarry particles with various mineral and metal content differed widely in
      potency to induce inflammatory cytokines (IL-6, IL-8 and TNF-alpha) in different
      types of lung cells. In this study we investigated if the observed cytokine
      responses were associated with the soluble or insoluble components of the stone
      particles and if there was a relationship between the differential cytokine
      release and generation of reactive oxygen species (ROS). Exposure of the human
      alveolar cell line A549 to the different particle leachates (pH 7.4 and 4.0) did
      not induce corresponding differential increases in the IL-8 release as observed
      with whole particles. Increase in ROS production, measured as dichlorofluorescein
      fluorescence, was only demonstrated after exposure of A549 cells to the pH 4.0
      extract from basalt. Furthermore, generation of ROS was found in neutrophils but
      not in A549 cells and primary macrophages after exposure to suspensions of the
      solid particles. However, no obvious differences in potency among the different
      particles were demonstrated. In summary, other mechanisms than particle-induced
      ROS formation seem to be responsible for the differential induction of IL-8.
      Furthermore, our findings indicate that the differential ability to induce IL-8
      release in lung cells is attributed to the solid components of the stone
      particles.

PMID- 11522372
TI  - Can toxicogenomics provide information on the bioreactivity of diesel exhaust
      particles?
AB  - Epidemiologists have linked increased cardio-respiratory hospital admissions,
      morbidity and mortality rates and increases in particulate matter with an
      aerodynamic diameter less than 10 microns (PM10) concentrations (Anderson et al.,
      1991). PM10 consist of a heterogeneous mixture of particles that include
      minerals, metal oxides, sea salt, biological components and soot. In urban
      locations, soot, especially ultrafine diesel exhaust particles (DEP), accounts
      for 20-80% by mass of the airborne PM10 arising from vehicular activities. In the
      experiment described here, control [NaCl] and 1.25 mg of DEP were instilled into
      rat lung and the responses assessed using changes in lung permeability,
      inflammation and epithelial cell markers in lavage fluid, with the addition of a
      new technique of gene expression profiling using macroarrays. The aim of the
      study was to use these macroarrays as a sensitive measurement of acute up- or
      down-regulation of genes that were taking place in the rat lung in response to
      the small instilled mass of DEP. DEP instillation caused a slight oedematous lung
      with no overt inflammation and ten out of a possible 207 (5%) rat stress genes
      were repeatedly changed in response to DEP instillation. Therefore, the
      conclusion from the macroarray analysis is in agreement with the conventional
      toxicology and suggest that DEP elicits a low bioreactive response in a healthy
      rat lung.

PMID- 11522373
TI  - Cytogenetic monitoring of croatian population occupationally exposed to a complex
      mixture of pesticides.
AB  - This paper describes a longitudinal study of possible genetic damage in Croatian
      workers occupationally exposed to a complex mixture of pesticides. The methods of
      choice were chromosomal aberration analysis, sister chromatid exchange analysis
      (SCE), micronucleus assay and comet assay. In order to determine primary
      genotoxic effects in workers, blood samples were taken after the workers spent 8
      months in the production of pesticides. During the production all subjects were
      simultaneously exposed to a complex mixture of pesticides containing atrazine,
      alachlor, cyanazine, 2,4-dichlorophenoxyacetic acid, and malathion. To detect DNA
      repair in lymphocytes of the same subjects the second series of blood samples was
      taken 8 months after the workers were removed from production. Regardless of the
      time sampling time the exposed workers showed an increased number of chromosomal
      aberrations, SCE frequency, micronucleus (MN) frequency, and values of comet
      assay parameters. After 8 months of non-exposure the workers showed a
      significantly decreased number of chromosomal aberrations, MN frequency, and DNA
      migration compared to the results of the first sampling, but it was still
      significantly higher than in controls. Furthermore, the SCE frequency in the
      exposed subjects did not drop after the 8 months of non-exposure, which indicates
      long-term exposure to a mixture of pesticides.

PMID- 11522374
TI  - L-tyrosine and nitric oxide synergize to prevent cytotoxic effects of superoxide.
AB  - We found previously that the nitric oxide donor DEA/NO enhanced lipid
      peroxidation, DNA fragmentation, and cytotoxicity in human bronchial epithelial
      cells (BEAS-2B) when they were cultured in LHC-8 medium containing the superoxide
      generating system hypoxanthine/xanthine oxidase (HX/XO). We have now discovered
      that DEA/NO's prooxidant action can be reversed by raising the L-tyrosine
      concentration from 30 to 400 microM. DEA/NO also protected the cells when they
      were cultured in Dulbecco's Modified Eagle's Medium (DMEM), whose standard
      concentration of L-tyrosine is 400 microM. Similar trends were seen with the
      colon adenoma cell line CaCo-2. Since HPLC analysis of cell-free DMEM or LHC-8
      containing 400 microM L-tyrosine, DEA/NO, and HX/XO revealed no evidence of L
      tyrosine nitration, our data suggest the existence of an as-yet uncharacterized
      mechanism by which L-tyrosine can influence the biochemical and toxicological
      effects of reactive nitrogen species.

PMID- 11522375
TI  - Primary culture system of adrenocortical cells from dogs to evaluate direct
      effects of chemicals on steroidogenesis.
AB  - The present study was conducted to confirm the usefulness of a primary culture
      system of adrenocortical cells from dogs for detecting the direct effects of the
      chemicals on adrenal cortex. Corticosteroid levels in the culture supernatant
      were measured using high-performance liquid chromatography (HPLC) following 24-h
      incubation with the chemicals. Ketoconazole, miconazole, metyrapone,
      aminoglutethimide, and 1-(o-chlorophenyl)-1-(p-chlorophenyl)-2,2-dichloroethane
      (o,p-DDD), which were known to inhibit cortisol production were evaluated in this
      system. Both viable cells and corticosteroid levels were decreased by o,p-DDD
      treatment. Other chemicals showed various inhibition patterns of corticosteroid
      levels as follows without affecting cell viability. Ketoconazole decreased total
      corticosteroids level by mainly due to the decreases in cortisol and 11
      deoxycortisol levels. Miconazole decreased cortisol and 11-deoxycortisol levels,
      however, slightly increased corticosterone level. Metyrapone decreased cortisol
      and corticosterone levels as 11-deoxycortisol and 11-deoxycorticosterone levels
      were increased. Aminoglutethimide decreased total corticosteroids level by mainly
      decreasing cortisol, corticosterone and 11-deoxycortisol levels. These results
      suggested that determination of the pattern of corticosteroid levels by HPLC in
      this system well reflected the mode of their action on steroidogenesis. Thus, we
      conclude this simple system was useful to determine the direct effects of
      chemicals on steroidogenesis in the adrenal cortex.

PMID- 11522377
TI  - Abamectin effects on aspartate aminotransferase and nitric oxide in rats.
AB  - Abamectin is widely used as an insecticide and an anthelmintic. A previous report
      indicated that abamectin was used to commit suicide and led to death in Taiwan.
      This investigation focused on the toxicological effects of abamectin on serum
      aspartate aminotransferase (AST) and nitrate/nitrite (NO) levels in rats. After
      rats were gavaged with abamectin ranging from 1 to 20 mg/kg/body weight, AST and
      NO levels were examined within 12 h. AST and NO levels were elevated in abamectin
      dosed rats in a dose-dependent manner. The least increase of AST corresponded to
      the highest enhancement of NO release at 6 h. A negative correlation coefficient
      (r=-0.55) between AST and NO was found. Both NG-nitro-L-arginine-methyl ester and
      aminoguanidine, inhibitors of nitric oxide synthase, increased the AST level
      induced by abamectin. These findings suggest that NO may be involved in the
      alteration of AST release induced by abamectin in rats.

PMID- 11522376
TI  - Induction of apoptotic cell death by a p53-independent pathway in neuronal SK-N
      MC cells after treatment with 2,2',5,5'-tetrachlorobiphenyl.
AB  - Apoptotic cell death is an active process, which is a critical feature of the
      regulated development of multicellular organisms. Polychlorinated biphenyls
      (PCBs) are ubiquitous environmental contaminants, some of which may be
      neurotoxic. This study investigates the 2,2', 5,5'-tetrachlorobiphenyl (PCB 52)
      induced apoptosis in human neuronal SK-N-MC cells, and the role of p53 in this
      response. Upon treatments with PCB 52, time- and concentration-dependent
      inhibition of the cell viability was observed. PCB 52 also caused apoptosis, as
      measured by cell morphology and DNA fragmentation. The capability of PCB 52 to
      induce apoptosis was associated with the proteolytic cleavage of specific target
      proteins, such as poly(ADP-ribose) polymerase (PARP) and beta-catenin proteins,
      suggesting the possible involvement of caspases. In general, DNA-damaging agents
      induce accumulation of the tumor suppressor protein p53, leading cells to either
      growth arrest in G1, or apoptosis. However, our data showed that both p53 and Bcl
      2 protein levels were decreased in a time-dependent manner during apoptosis after
      exposure to PCB 52. These results suggest that PCB 52 induced a p53-independent
      apoptosis in these cells.

PMID- 11522378
TI  - Gender-related differences in subacute fumonisin B1 hepatotoxicity in BALB/c
      mice.
AB  - Fumonisin B1 (FB1), a potent mycotoxin prevalent in corn, is a carcinogen and
      causative agent of various animal diseases. Species and sex variations to chronic
      FB1 toxicity have been reported. Free sphingoid bases and cytokine levels are the
      two major biochemical alterations of FB1 in vivo and may explain any sex
      differences in FB1 toxicity. Male and female BALB/c mice (5/group) were injected
      subcutaneously with either saline vehicle or 2.25 mg/kg/day of FB1 for 5 days.
      One day after the last injection females showed a greater increase in circulating
      alanine aminotransferase and greater number of apoptotic cells in liver after FB1
      treatment than males, indicating greater hepatotoxicity. Peripheral leukocytic
      counts, including neutrophils, were increased in females only after FB1
      treatment. The increased toxicity in females correlated with a greater increase
      of sphinganine and sphingosine levels in liver after FB1 treatment compared to
      males. No sex differences in kidney sphinganine or sphingosine levels were
      observed after FB1 treatment. Previously we have shown the induction of tumor
      necrosis factor alpha (TNFalpha) in FB1-induced hepatotoxicity. While in males
      FB1 treatment caused increased expression of TNFalpha, interleukin (IL)-12 p40,
      interferon gamma (IFNgamma), IL-1beta, IL-6 and IL-10, females showed an
      increased expression of IL-6 only, and a downward modulation of IFNgamma,
      indicating gender differences in cytokine pathways in liver activated by FB1. The
      basal expression of TNFalpha, IL-12 p40, IL-1beta and IFNgamma in liver of
      females was higher compared to males. Gender differences in alterations of free
      sphingoid bases and cytokine modulation after FB1 treatment suggest their
      possible involvement in sex-dependent differential hepatotoxicity in mice.

PMID- 11522379
TI  - Subchronic cadmium treatment affects the abundance and arrangement of
      cytoskeletal proteins in rat renal proximal tubule cells.
AB  - Disfunction of proximal tubules (PT) in cadmium (Cd) nephrotoxicity in mammals
      results from the diminished functional capacity of brush-border membrane (BBM)
      caused by (a) direct inhibition of BBM transporters by Cd, (b) shortening and
      loss of microvilli, and (c) loss of specific BBM transporters. The loss of
      transporters may partially result from impaired intracellular vesicle recycling
      due to loss or/and inhibition of vacuolar H+-ATPase in the PT cell organelles.
      Cytoskeleton plays an important role in vesicle-mediated recycling and processing
      of BBM transporters in PT cells. Experiments in vitro have indicated that Cd may
      affect the state of polymerization of some cytoskeletal proteins. In this work we
      studied the in vivo effect of CdCl2-treatment in rats (2 mg Cd/kg b. m., s.c.,
      daily for 14 days) upon abundance and arrangement of actin filaments, actin
      bundling protein villin, and microtubules (MT) in PT cells. Cd-treatment elicited
      a dramatic accumulation of Cd in the kidney cortex (200 microg/g tissue wet mass
      after 14 days) and a strongly increased abundance of metallothionein in PT cells.
      As revealed by immunocytochemistry in tissue cryosections, the staining intensity
      of actin and villin in PT cells of Cd-treated rats was generally decreased,
      without a marked change in their intracellular distribution, whereas MT became
      largely irregular, diminished in most cells, and lost in many cells. However, the
      immunoblots revealed an increased content of villin and alpha-tubulin in cortical
      tissue homogenates from Cd-treated rats, thus indicating an impaired bundling of
      actin and greatly depolymerized MT in cells intoxicated with Cd. The partial loss
      of apical actin and villin in PT cells of Cd-treated rats may reflect (or cause)
      shortening and loss of microvilli, whereas derangement and depolymerization of MT
      may contribute to the impairment of intracellular recycling of BBM proteins, and
      lead to the loss of BBM transporters.

PMID- 11522380
TI  - Carbon tetrachloride-induced changes in the activity of phase II drug
      metabolizing enzyme in the liver of male rats: role of antioxidants.
AB  - Glutathione S-transferases and glutathione play an important role in the
      detoxification of most toxic agents. In the present study, the protective effects
      of some antioxidants (L-ascorbic acid (AA), vitamin E (VE) or garlic) on carbon
      tetrachloride-induced changes in the activity of alanine amino transferase (ALT),
      aspartate amino transferase (AST), glutathione S-transferase (GST), and the level
      of glutathione (GSH) and thiobarbituric acid reactive substances (TBARS) were
      studied. The activities of ALT, and AST were assayed in plasma, whereas the
      activity of GST and the levels of GSH and TBARS were determined in the livers of
      rats. The current study included two experiments. In the first experiment,
      animals received single oral dose of CCl4 (400 mg/kg body weight) after
      administration of AA (100 mg/kg b.w.), VE (100 mg/kg b.w.) or garlic (800 mg/kg
      b.w.) as single oral doses. In the second experiment, rats received repeated oral
      doses of antioxidants for 12 consecutive days followed by a single oral dose of
      CCl4 on the 13th day and killed after that by 24 h. Treatment of male rats with
      CCl4 significantly increased the activity of ALT and AST in plasma, and the
      levels of both GSH and TBARS in the liver. On the other hand, CCl4 inhibited the
      activity of GST after single dose treatment. Single-dose treatments of rats with
      AA, VE or garlic prior to the administration of CCl4 could not restore the
      alterations in the activity of ALT and AST caused by CCl4 to the normal control
      level. However, repeated dose treatments with these agents restored such
      alterations to the normal level. We observed that VE is more effective than AA
      and garlic in restoring the inhibition of GST activity caused by CCl4 to the
      normal level after single dose treatments. On the other hand, AA and VE are more
      effective than garlic in restoring the induced TBARS level caused by CCl4 to the
      normal control level after repeated dose treatments. It has been observed that
      the tested antioxidants were able to antagonize the toxic effects of CCl4, and
      such counteracting effects were more pronounced when they were administered as
      repeated doses prior to administration of CCl4.

PMID- 11522381
TI  - Effect of benzoyl peroxide on antioxidant status, NF-kappaB activity and
      interleukin-1alpha gene expression in human keratinocytes.
AB  - Benzoyl peroxide (BP) is used as a topical treatment for acne. Besides its anti
      bacterial activity, the exact molecular mechanisms underlying its mode of action
      are not fully understood. In the current study, the effects of BP on cell
      viability, antioxidant status and, IL-1 and IL-8 gene expression were
      investigated in HaCaT keratinocytes. Keratinocytes incubated for 24 h with BP
      exhibited a dose-dependent cytotoxicity at concentrations above 250 microM.
      Furthermore, in the presence of 300 microM BP about 50% of the cellular vitamin E
      was depleted within the first 30 min. The intracellular ratio of oxidized to
      reduced glutathione (GSSG/GSH) was increased significantly starting 6 h after BP
      treatments indicating that BP reacts rapidly with targets in the cell membrane
      and more slowly with those in the cytosol. NF-kappaB transactivation was not
      significantly affected by BP. However, BP treatment of HaCaT keratinocytes
      resulted in a dose-dependent increase in IL-1alpha gene expression whereas no
      changes in IL-8 mRNA levels were observed. These results demonstrate that BP
      induces an inflammatory reaction mediated by oxidative stress by a pathway
      independent of the redox-sensitive transcription factor NF-kappaB.

PMID- 11522383
TI  - The alpha-Gal epitope (Galalpha1-3Galbeta1-4GlcNAc-R) in xenotransplantation.
AB  - Many patients with failing organs (e.g., heart, liver or kidneys), do not receive
      the needed organ because of an insufficient number of organ donors. Pig
      xenografts have been considered as an alternative source of organs for
      transplantation. The major obstacle currently known to prevent pig to human
      xenotransplantation is the interaction between the human natural anti-Gal
      antibody and the alpha-gal epitope (Galalpha1-3Galbeta1-4GlcNAc-R), abundantly
      expressed on pig cells. This short review describes the characteristics of anti
      Gal and of the alpha-gal epitope, their role in inducing xenograft rejection and
      some experimental approaches for preventing this rejection.

PMID- 11522384
TI  - ABH and Lewis histo-blood group antigens, a model for the meaning of
      oligosaccharide diversity in the face of a changing world.
AB  - Antigens of the ABH and Lewis histo-blood group family have been known for a long
      time. Yet their biological meaning is still largely obscure. Based on the
      available knowledge about the genes involved in their biosynthesis and about
      their tissue distribution in humans and other mammals, we discuss here the
      selective forces that may maintain or propagate these oligosaccharide antigens.
      The ABO, alpha 1,2fucosyltransferase and alpha 1,3fucosyltransferase enzyme
      families have been generated by gene duplications. Members of these families
      contribute to biosynthesis of the antigens through epistatic interactions. We
      suggest that the highly polymorphic genes of each family provide intraspecies
      diversity that allows coping with diverse and rapidly evolving pathogens. In
      contrast, the genes of low frequency polymorphism are expected to play roles at
      the cellular level, although they may be dispensable at the individual level. In
      addition, some members of these three gene families are expected to be
      functionally redundant and may either provide a reservoir for additional
      diversity in the future or become inactivated. We also discuss the role of the
      ABH and Lewis histo-blood group antigens in pathologies such as cancer and
      cardiovascular diseases, but argue that it is merely incidental and devoid of
      evolutionary impact.

PMID- 11522385
TI  - Nucleocytoplasmic O-glycosylation: O-GlcNAc and functional proteomics.
AB  - The molecular complexity that defines different cell types and their biological
      responses occurs at the level of the cell's proteome. The recent increase in
      availability of genomic sequence information is a valuable tool for the field of
      proteomics. While most proteomic studies focus on differential expression levels,
      post-translational modifications such as phosphorylation, glycosylation, and
      acetylation, provide additional levels of functional complexity to the cell's
      proteome. The reversible post-translational modification O-linked beta-N
      acetylglucosamine (O-GlcNAc) is found on serines and threonines of nuclear and
      cytoplasmic proteins. It appears to be as widespread as phosphorylation. While
      phosphorylation is recognized as a fundamental mechanism for controlling protein
      function, less is known about the specific roles of O-GlcNAc modification.
      However, evidence is building that O-GlcNAc may compete with phosphate at some
      sites of attachment. Aberrant O-GlcNAc modification has been linked to several
      disease states, including diabetes and Alzheimer's disease. Regulated enzymes
      catalyzing the addition (O-GlcNAc transferase, OGT) and removal (O-GlcNAcase) of
      the modification have been cloned and OGT is required for life at the single cell
      level. Here we review the properties of O-GlcNAc that suggest it is a regulatory
      modification analogous to phosphorylation. We also discuss the use of comparative
      functional proteomics to elucidate functions for this ubiquitous intracellular
      carbohydrate modification.

PMID- 11522386
TI  - O-GlcNAc expression in developing and ageing mouse brain.
AB  - In order to understand whether there is a specific role for the posttranslational
      N-acetylglucosamine modification linked O-glycosidically (O-GlcNAc) to serine and
      threonine residues of proteins during development and/or ageing of the brain, we
      investigated the O-GlcNAc expression of early postnatal cerebellar neurons as
      well as of mouse brain of different ages. In all cells either in culture or of
      cryosections mainly the nuclei and nuclear membranes were stained with an O
      GlcNAc specific monoclonal antibody. In cerebellar neurons in culture the level
      of expression could be manipulated by directly interfering with either the
      biosynthesis of GlcNAc or the removal of O-GlcNAc from proteins confirming the
      dynamic nature of this protein modification. O-GlcNAc was ubiquitously expressed
      in mouse brains from embryonic day 10 until late adulthood with some variations
      in expression strength from cell to cell. In addition, no significant difference
      in O-GlcNAc expression of subcellular fractions from brains of mice which age at
      an accelerated rate could be detected compared to normal mice. Taken together
      these observations support the view that the O-GlcNAc modification has important
      functional roles for physiological processes of neural cell throughout
      development, in adulthood and ageing.

PMID- 11522387
TI  - Glycobiology of surface layer proteins.
AB  - Over the last two decades, a significant change of perception has taken place
      regarding prokaryotic glycoproteins. For many years, protein glycosylation was
      assumed to be limited to eukaryotes; but now, a wealth of information on
      structure, function, biosynthesis and molecular biology of prokaryotic
      glycoproteins has accumulated, with surface layer (S-layer) glycoproteins being
      one of the best studied examples. With the designation of Archaea as a second
      prokaryotic domain of life, the occurrence of glycosylated S-layer proteins had
      been considered a taxonomic criterion for differentiation between Bacteria and
      Archaea. Extensive structural investigations, however, have demonstrated that S
      layer glycoproteins are present in both domains. Among Gram-positive bacteria, S
      layer glycoproteins have been identified only in bacilli. In Gram-negative
      organisms, their presence is still not fully investigated; presently, there is no
      indication for their existence in this class of bacteria. Extensive biochemical
      studies of the S-layer glycoprotein from Halobacterium halobium have, at least in
      part, unravelled the glycosylation pathway in Archaea; molecular biological
      analyses of these pathways have not been performed, so far. Significant
      observations concern the occurrence of unusual linkage regions both in archaeal
      and bacterial S-layer glycoproteins. Regarding S-layer glycoproteins of bacteria,
      first genetic data have shed some light into the molecular organization of the
      glycosylation machinery in this domain. In addition to basic S-layer glycoprotein
      research, the biotechnological application potential of these molecules has been
      explored. With the development of straightforward molecular biological methods,
      fascinating possibilities for the expression of prokaryotic glycoproteins will
      become available. S-layer glycoprotein research has opened up opportunities for
      the production of recombinant glycosylation enzymes and tailor-made S-layer
      glycoproteins in large quantities, which are commercially not yet available.
      These bacterial systems may provide economic technologies for the production of
      biotechnologically and medically important glycan structures in the future.

PMID- 11522388
TI  - Glycobiology of Plasmodium falciparum.
AB  - The human malaria parasite, Plasmodium falciparum, has as its only glycoconjugate
      GPI anchors. These structures, present in essentially all parasite surface
      proteins, are associated with disease pathology. In contrast, the parasite
      depends for essential recognition events on saccharides associated with host cell
      glycoproteins and proteoglycans.

PMID- 11522389
TI  - A challenge to the ultrasensitive chemical method for the analysis of oligo- and
      polysialic acids at a nanogram level of colominic acid and a milligram level of
      brain tissues.
AB  - Polysialic acid (polySia) is a functional epitope and is known: 1) to regulate
      normal fertilization of lower vertebrates and invertebrates; 2) to be expressed
      on neural cell adhesion molecule (NCAM) when the formation or re-arrangement of
      nervous tissues takes place during embryonic stages as well as in adults of
      higher vertebrates; and 3) to be re-expressed in several human tumors. Thus,
      polySia serves as oncodevelopmental antigen. To date sensitive biochemical
      diagnostic probes (antibodies and endo-N-acylneuraminidase) to detect polySia are
      known. However, these reagents are not commercially available yet and they are
      only reactive to specific types of polySia structure. Moreover, precise
      information not only on diversity but also on the length or degree of
      polymerization (DP) of extended polySia chains is considered important in
      understanding the molecular mechanism of biosynthesis of polySia chains and fine
      tuning of NCAM-NCAM adhesive interaction by polySia chain but cannot be obtained
      with these biochemical probes. We have been continuously making efforts to
      develop and improve the sensitivity of chemical methods for polySia analysis
      toward these challenging problems. This article presents our most recently
      developed chemical method for polySia analysis and its use in obtaining new
      information on DP of colominic acid samples and polySia chains present in rat
      brain tissues with the highest sensitivity that has ever been attained.

PMID- 11522390
TI  - N-glycolylneuraminic acid deficiency in humans.
AB  - Classic studies suggested that the common mammalian sialic acid N
      glycolylneuraminic acid (Neu5Gc) is an oncofetal antigen in humans, being
      immunogenic in adult humans and yet apparently expressed in human fetuses and
      tumors. We and others have recently found that the human deficiency of Neu5Gc can
      be explained by an inactivating mutation in the gene encoding CMP-N
      acetylneuraminic acid hydroxylase. Thus, Neu5Gc is not an oncofetal antigen in
      the classical sense, and other explanations must be found for the observed
      expression pattern. This review provides an update on this matter, and considers
      a variety of other old and new questions that arise from it.

PMID- 11522391
TI  - N-Glycolylneuraminic acid in human tumours.
AB  - N-Glycolylneuraminic acid (Neu5Gc) is an abundant sialic acid, occurring in the
      glycoconjugates of most deuterostome animals. Homo sapiens is a notable
      exception, since Neu5Gc is effectively absent from normal human tissues. This is
      due to a deletion in the human gene coding for CMP-Neu5Ac hydroxylase, the enzyme
      usually responsible for Neu5Gc biosynthesis. Despite this mutation, persistent
      reports in the literature suggest that Neu5Gc occurs in the glycoconjugates of
      many human tumours, where it might be responsible for the formation of so-called
      Hanganutziu-Deicher antibodies. However, the variety of systems studied and the
      various experimental approaches adopted have yielded a complex picture of Neu5Gc
      occurrence in human neoplasias. The aim of this paper is therefore to provide a
      critical review of the evidence for Neu5Gc in human tumours, paying particular
      attention to the analytical methods employed. The possible clinical applications
      of Neu5Gc-containing glycoconjugates and Hanganutziu-Deicher antibodies in the
      diagnosis and treatment of breast cancer and melanoma are also discussed. In view
      of the lack of CMP-Neu5Ac hydroxylase in human cells, alternative metabolic
      pathways for the biosynthesis of glycoconjugate-bound Neu5Gc are considered.

PMID- 11522392
TI  - Roles, regulation, and mechanism of polysialic acid function during neural
      development.
AB  - The polysialylated form of the neural cell adhesion molecule (PSA-NCAM) appeared
      during the evolution of vertebrates as a new mechanism for regulation of cell
      interactions. This large and abundant glycoprotein can exert steric effects at
      the cell surface that lead to the attenuation of cell-cell bonds mediated not
      only by NCAM but also a variety of other adhesion receptors. PSA-NCAM expression
      changes both as a result of developmental programs and physiological inputs. This
      global modulation of cell-cell attachment has been shown to facilitate cell
      migration, axon pathfinding and targeting, and plastic changes in the embryonic
      and adult nervous system.

PMID- 11522393
TI  - Mannose-binding plant lectins: different structural scaffolds for a common sugar
      recognition process.
AB  - Mannose-specific lectins are widely distributed in higher plants and are believed
      to play a role in recognition of high-mannose type glycans of foreign micro
      organisms or plant predators. Structural studies have demonstrated that the
      mannose-binding specificity of lectins is mediated by distinct structural
      scaffolds. The mannose/glucose-specific legume (e.g., Con A, pea lectin) exhibit
      the canonical twelve-stranded beta-sandwich structure. In contrast to legume
      lectins that interact with both mannose and glucose, the monocot mannose-binding
      lectins (e.g., the Galanthus nivalis agglutinin or GNA from bulbs) react
      exclusively with mannose and mannose-containing N-glycans. These lectins possess
      a beta-prism structure. More recently, an increasing number of mannose-specific
      lectins structurally related to jacalin (e.g., the lectins from the Jerusalem
      artichoke, banana or rice), which also exhibit a beta-prism organization, were
      characterized. Jacalin itself was re-defined as a polyspecific lectin which, in
      addition to galactose, also interacts with mannose and mannose-containing
      glycans. Finally the B-chain of the type II RIP of iris, which has the same beta
      prism structure as all other members of the ricin-B family, interacts
      specifically with mannose and galactose. This structural diversity associated
      with the specific recognition of high-mannose type glycans highlights the
      importance of mannose-specific lectins as recognition molecules in higher plants.

PMID- 11522394
TI  - Analysis of the interaction between lectins and tetra- and tri-saccharide mimics
      of the Sd(a) determinant by surface plasmon resonance detection.
AB  - The binding properties of a spacer-linked synthetic Sd(a) tetrasaccharide beta-D
      GalpNAc-(1-->4)-alpha-Neu5Ac-(2-->3)]-beta-D-Galp-(1-->4)-beta-D-GlcpNAc-(1-->O)
      (CH(2))(5)-NH(2) (1), two tetrasaccharide mimics beta-D-Galp-(1-->4)-alpha-Neu5Ac
      (2-->3)]-beta-D-Galp-(1-->4)-beta-D-GlcpNAc-(1-->O)-(CH(2))(5)-NH(2) (2) and beta
      D-GlcpNAc-(1-->4)-alpha-Neu5Ac-(2-->3)]-beta-D-Galp-(1-->4)-beta-D-GlcpNAc-(1-
      >O)-(CH(2))(5)-NH(2) (3), and two trisaccharide mimics beta-D-GalpNAc-(1-->4)-3-O
      (SO(3)H)-beta-D-Galp-(1-->4)-beta-D-GlcpNAc-(1-->O)-(CH(2))(5)-NH(2) (4) and beta
      D-GalpNAc-(1-->4)-3-O-(CH(2)COOH)-beta-D-Galp-(1-->4)-beta-D-GlcpNAc-(1-->O)
      (CH(2))(5)-NH(2) (5) with lectins from Dolichos biflorus (DBL), Maackia amurensis
      (MAL), Phaseolus limensis (PLL), Ptilota plumosa (PPL), Ricinus communis 120
      (RCL120) and Triticum vulgaris (wheat germ agglutinin, WGA) have been
      investigated by surface plasmon resonance (SPR) detection. MAL, PPL, RCL120 and
      WGA did not display any binding activity with compounds 1-5. However, DBL and
      PLL, both exhibiting GalNAc-specificity, showed strong binding activity with
      compounds 1, 4 and 5, and 1, 3, 4 and 5, respectively. The results demonstrate
      that SPR is a very useful analysis system for identifying biologically relevant
      oligosaccharide mimics of the Sd(a) determinant.

PMID- 11522395
TI  - Probing the cons and pros of lectin-induced immunomodulation: case studies for
      the mistletoe lectin and galectin-1.
AB  - When imagining to monitor animal cells through a microscope with resolution at
      the molecular level, a salient attribute of their surfaces will be the abundance
      of glycan chains. They present galactosides at their termini widely extending
      like tentacles into the extracellular space. Their spatial accessibility and
      their potential for structural variability endow especially these glycan parts
      with capacity to act as docking points for molecular sensors (sugar receptors
      such as lectins). Binding and ligand clustering account for transmission of post
      binding signals into the cell interior. The range of triggered activities has
      turned plant lectins into popular tools in cell biology and immunology. Potential
      for clinical application has been investigated rigorously only in recent years.
      As documented in vitro and in vivo for the galactoside-specific mistletoe lectin,
      its apparent immunomodulatory capacity reflected in upregulation of production of
      proinflammatory cytokines will not necessarily be clinically favorable but a
      double-edged sword. In fact, lectin application has been shown to stimulate tumor
      growth in cell lines, histocultures of human tumors and in two animal models
      using chemical carcinogenesis or tumor transplantation. When testing
      immunological effects of the endogenous lectin galectin-1, protection against
      disorders mediated by activated T cells came up for consideration. Elimination of
      these cells via CD7-dependent induction of apoptosis, and a shift to the Th2
      response by the galectin, are factors to ameliorate disease states. This result
      encourages further efforts with other galectins. Functional redundancy,
      synergism, diversity or antagonism among galectins are being explored to
      understand the actual role of this class of endogenous lectins in inflammation.
      Regardless of the results of further preclinical testing for galectin-1, these
      two case studies break new ground in our understanding how glycans as ligands for
      lectins convey reactivity to immune cells, with impact on the course of a tumor
      or autoimmune disease.

PMID- 11522396
TI  - Galectins as modulators of cell adhesion.
AB  - The galectins are a family of carbohydrate-binding proteins that are distributed
      widely in metazoan organisms. Each galectin exhibits a specific pattern of
      expression in various cells and tissues, and expression is often closely
      regulated during development. Although these proteins are found mainly in the
      cell cytoplasm, some are secreted from cells and interact with appropriately
      glycosylated proteins at the cell surface or within the extracellular matrix.
      These receptors include cell-adhesion molecules such as integrins, and matrix
      glycoproteins such as laminin and fibronectin isoforms. Recent studies have
      increased understanding of the roles of the galectins in regulating cell-cell and
      cell-matrix adhesion. These interactions are critically involved in modulation of
      normal cellular motility and polarity and during tissue formation, and loss of
      adhesive function is implicated in several disease states including tumour
      progression, inflammation and cystic development in branching epithelia such as
      kidney tubules. This review discusses recent progress in defining the
      specificities and mechanisms of action of secreted galectins as multifunctional
      cell regulators.

PMID- 11522397
TI  - Brain gangliosides: functional ligands for myelin stability and the control of
      nerve regeneration.
AB  - Gangliosides, sialylated glycosphingolipids which are the predominant glycans on
      vertebrate nerve cell surfaces, are emerging as components of membrane rafts,
      where they can mediate important physiological functions. Myelin associated
      glycoprotein (MAG), a minor constituent of myelin, is a sialic acid binding
      lectin with two established physiological functions: it is involved in myelin
      axon stability and cytoarchitecture, and controls nerve regeneration. MAG is
      found selectively on the myelin membranes directly apposed to the axon surface,
      where it has been proposed to mediate myelin-axon interactions. Although the
      nerve cell surface ligands for MAG remain to be established, evidence supports a
      functional role for sialylated glycoconjugates. Here we review recent studies
      that reflect on the role of gangliosides, sialylated glycosphingolipids, as
      functional MAG ligands. MAG binds to gangliosides with the terminal sequence
      'NeuAc alpha 3Gal beta 3GalNAc' which is found on the major nerve gangliosides
      GD1a and GT1b. Gangliosides lacking that terminus (e.g., GM1 or GD1b), or having
      any biochemical modification of the terminal NeuAc residue fail to support MAG
      binding. Genetically engineered mice lacking the GalNAc transferase required for
      biosynthesis of the 'NeuAc alpha 3Gal beta 3GalNAc' terminus have grossly
      impaired myelination and progressive neurodegeneration. Notably the MAG level in
      these animals is dysregulated. Furthermore, removal of NeuAc residues from nerve
      cells reverses MAG-mediated inhibition of neuritogenesis, and neurons from mice
      lacking the 'NeuAc alpha 3 Gal beta 3GalNAc' terminus have an attenuated response
      to MAG. Cross-linking nerve cell surface gangliosides can mimic MAG-mediated
      inhibition of nerve regeneration. Taken together these observations implicate
      gangliosides as functional MAG ligands.

PMID- 11522398
TI  - Structural analysis of glycolipids from Borrelia burgdorferi.
AB  - In this study the lipids of Borrelia burgdorferi, the causative agent of Lyme
      disease, were analyzed. Lipids comprise about 25-30% of the cell dry weight. The
      lipid fraction could be separated by HPTLC into 11 components. Staining of these
      components revealed two glycolipids and two phospholipids. The glycolipids
      represented about 50% of the total lipids and comprised only galactose as
      monosaccharide constituents. By means of mass spectrometric and gas
      chromatographic analysis both glycolipids could be identified as alpha-galactosyl
      diacylglycerolipids with different fatty acid compositions. The phospholipids
      were identified as phosphatidylcholine and phosphatidylglycerol. Immunoassays
      with sera from patients with Lyme disease showed antibody reactivity only to the
      glycolipids, which was present in all stages of the disease. Other lipid
      components seemed to be non-immunogenic in Lyme disease. The glycolipids of B.
      burgdorferi may be, thus, considered promising candidates for diagnosis and
      possibly also for vaccination.

PMID- 11522399
TI  - Chemical synthesis of a P(k)-antigenic globotriose analogue with a functionalized
      aglycon.
AB  - 6-Aminohexyl alpha-D-galactopyranosyl-(1-->4)-beta-D-galactopyranosyl-(1-->4)
      beta-D-glucopyranoside (2), a globotriose analogue with a functionalized aglycon,
      was synthesized, using alpha-D-galactopyranosyluronic acid-(1-->4)-D
      galactopyranosyluronic acid [di-GalA (3)] as the starting material, which is
      commercially available or can be readily prepared from pectin.

PMID- 11522401
TI  - c-DNA vaccination against parasitic infections: advantages and disadvantages.
AB  - Recently developed technology for DNA vaccination appears to offer the good
      prospect for the development of a multivalent vaccines that will effectively
      activate both the humoral and cell mediated mechanisms of the immune system.
      Currently, DNA vaccination against such important parasitic diseases like
      malaria, leishmaniosis, toxoplasmosis, cryptosporidiosis, schistosomosis,
      fasciolosis offers several new opportunities. However, the outcome of vaccination
      depends very much on vaccine formulations, dose and route of vaccine delivery,
      and the species and even strain of the vaccinated host. To overcome these
      problems much research is still needed, specifically focused on cloning and
      testing of new c-DNA sequences in the following: genome projects: different ways
      of delivery: design of vectors containing appropriate immunostimulatory sequences
      and very detailed studies on safety.

PMID- 11522402
TI  - Control of coccidiosis in chickens by vaccination.
AB  - Control of coccidiosis in chickens has relied upon managerial measurements and
      the prophylactic use of coccidiostatic drugs. With the emergence of Eimeria
      strains that are resistant to these drugs the use and number of commercially
      available vaccines has increased. In this review various aspects that contribute
      to the development of coccidiosis are discussed, and an overview of the currently
      marketed coccidiosis vaccines is presented. Three groups of vaccines can be
      distinguished based on the characteristics of the Eimeria species included in the
      products: vaccines based on live virulent strains, vaccines based on live
      attenuated strains, and vaccines based on live strains that are relatively
      tolerant to the use of ionophores. These latter vaccines combine the early
      protective effect of ionophore treatment with the late protective effect of
      vaccination. The impact of future developments such as recombinant-DNA vaccines
      and changes in consumer's attitude towards broiler production are discussed.

PMID- 11522403
TI  - Vaccination against gastrointestinal nematode parasites of ruminants using gut
      expressed antigens.
AB  - To date, proteins isolated from the surface of the gut of gastrointestinal
      nematodes, particularly Haemonchus contortus, have generally proved to be useful
      protective antigens and several are being progressed towards recombinant protein
      based vaccines. This paper describes the properties of some of the most promising
      antigens and summarises their performance in laboratory and field based trials.
      The antigens described include contortin, H11, H-gal-GP, GPI and cysteine
      proteinases. In addition, the discussion addresses the utility of selected
      antigens to protect against co-infecting nematode species such as Teladorsagia
      circumcincta and against related nematode infections such as Ostertagia ostertagi
      in cattle.

PMID- 11522404
TI  - Immunity to filarial nematodes.
AB  - Mosquito-borne filarial nematodes cause the severe, debilitating disease of human
      lymphatic filariasis. In areas endemic for this disease, differential responses
      range from putative immunity through asymptomatic microfilaraemic infection to
      chronic pathology. Current research in mouse models of infection is elucidating
      the immunological mechanisms that can lead to immunity against this disease. In
      this review, the importance of different immunological pathways are discussed in
      relation to their role in human disease and in terms of their ability to kill
      separate developmental stages of the filarial parasite.

PMID- 11522405
TI  - Cytokine regulation of resistance and susceptibility to intestinal nematode
      infection - from host to parasite.
AB  - Intestinal nematode infection is one of the most common forms of parasite
      infection worldwide. Both man and domestic stock suffer considerable morbidity
      from these infectious agents. The majority of our current understanding of the
      host parasite relationship to gut dwelling nematodes comes from well-defined
      laboratory models. One of the most informative over recent years has been study
      of whipworm infection in the mouse, Trichuris muris (T. muris). Infection in
      inbred strains of mouse shows a spectrum of response phenotypes reflecting the
      variation observed under natural conditions in the wild. Resistance and worm
      expulsion is mediated by CD4+ T helper two cells with a dominant role for
      interleukin (IL)-13. The effector mechanisms responsible for worm expulsion
      remain undefined but new evidence suggests a role for tumour necrosis factor
      alpha (TNF-alpha). Susceptibility to chronic infection is mediated through a T
      helper 1 (Th1) response characterised through the secretion of interferon gamma
      (IFN-gamma). A major new role for IL-18 has been defined in induction of a Th1
      response through a novel down-regulation of IL-13. Moreover, progression to
      chronic infection may involve the parasite itself. T. muris secretes a protein
      that shares epitopes with host IFN-gamma, which may interfere with host
      protective cytokine, mediated protection and thus, promotes its own survival.

PMID- 11522407
TI  - Toxoplasma gondii induction of interleukin-12 is associated with acute virulence
      in mice and depends on the host genotype.
AB  - The intracellular parasite Toxoplasma gondii can influence host resistance by
      modulating immune functions in various cell types. The stimulation of interleukin
      (IL)-12 production in macrophages, dendritic cells and neutrophils by T. gondii
      has been implicated to be important for skewing anti-parasite immunity early
      after infection as well as in mediating the pathologic effects induced by the
      parasite. The present study demonstrates secretion of IL-12 p40 and the bioactive
      p70 heterodimer by inflammatory macrophages following exposure to live Toxoplasma
      or tachyzoite lysate. Parasite induction of IL-12 occurred in a dose-dependent
      manner. Predigestion of T. gondii lysate with proteinase K abrogated its IL-12
      inducing activity, thus indicating that a parasite protein(s) triggers this
      response. Macrophages from various mouse inbred strains showed a differential
      responsiveness: cells from T. gondii-susceptible mice released more IL-12 upon
      toxoplasmic challenge than those from resistant mice, although the infection rate
      and intracellular parasite growth were similar. In triggering macrophage
      production of IL-12, tachyzoites proved superior to bradyzoites prepared from the
      same T. gondii isolate. Furthermore, parasites of a mouse-virulent isolate became
      less efficient inducers of IL-12 following attenuation. The parallel loss in
      macrophage stimulation in vitro and acute virulence in vivo suggests a linkage of
      both parasite capacities. Together with the correlation on host side between the
      genotype-dependent mouse susceptibility to infection and cellular responsiveness
      to the parasite trigger, these findings indicate that an overproduction of
      parasite-induced IL-12 might represent a basic mechanism of T. gondii
      pathogenicity.

PMID- 11522406
TI  - Comparison of the vaccine efficacy of gamma-irradiated Schistosoma japonicum
      cercariae with the defined antigen Sj62(IrV-5) in pigs.
AB  - Development of a vaccine against Schistosoma japonicum which can protect both man
      and the domestic animal zoonotic reservoirs of infection would be an invaluable
      tool in attempts to control this infection in those areas in which conventional
      control methods have failed to break transmission. The pig is a natural host of
      S. japonicum and because of its anatomical and immunological similarities to
      humans, it is a potentially valuable host for studies on S. japonicum in
      particular and schistosomes in general. Radiation-attenuated cercariae are highly
      effective in inducing immunity in experimental schistosomosis and there are
      promising reports of partial protection against schistosomes with recombinant
      derived individual antigens. In the present study we have set out to establish a
      protocol for inducing protection with gamma-irradiated cercariae in pigs and to
      assess the protective capacity of recombinant and naked DNA formulations of Sj62,
      a 62kDa region of S. japonicum myosin. The corresponding S. mansoni version or
      Sj62, recombinant IrV-5, has previously been implicated in irradiated vaccine
      immunity in S. mansoni infections and has been shown to induce high levels of
      immunity in a variety of hosts. Groups of pigs were immunised three times at 2
      week intervals with 2000 cercariae irradiated at 20krad, with Sj62 as a
      recombinant (rSj62) incorporated in Freund's adjuvant, a micellar preparation, or
      as a naked DNA construct. Vaccination with irradiated cercariae did not induce
      significant anti-Sj62 antibody but following intramuscular challenge with 2000
      cercariae, the vaccinated pigs showed >95% resistance as assessed by reduced
      faecal egg output, worm tissue egg burdens and also reduced septal fibrosis.
      Immunisation with each of the Sj62 formulations induced significant anti-Sj62
      antibody responses, the highest titre (>12,800) being with the Freund's
      preparation but none of the Sj62-immunised groups showed significant resistance
      to challenge. The data suggest that Sj62 shows little promise as a vaccine
      candidate for schistosomosis.

PMID- 11522408
TI  - Vaccination of dogs against heterologous Babesia canis infection using antigens
      from culture supernatants.
AB  - Soluble parasite antigens (SPA) from European Babesia canis can be used to
      protect dogs against a homologous but not heterologous challenge infection. In
      this study it is shown that when dogs are vaccinated with a mixture of SPA from
      both, a European B. canis isolate and a South African Babesia rossi isolate,
      protective immunity against heterologous B. canis infection is induced. Three
      groups of five beagle dogs each were vaccinated twice with graded doses of SPA
      derived from in vitro cultures of B. canis and B. rossi, with a 3-week interval.
      Saponin was used as adjuvant. Three weeks after booster vaccination immunological
      responsiveness against heterologous B. canis antigen was measured by
      seroconversion against infected erythrocytes and lymphocyte transformation using
      SPA. Upon vaccination dogs produced antibodies against infected erythrocytes and
      lymphoblastogenic responses against SPA in a dose-dependent manner. Dogs were
      then challenged with heterologous B. canis parasites. Dogs appeared to be
      protected against challenge infection, which was reflected in less severe
      decrease of packed cell volume (PCV) and reduced clinical signs. The level of
      protection to clinical signs (but not excessive PCV drop) was related to the
      level of SPA in plasma and spleen size, and not related to peripheral
      parasitaemia. The results suggest that vaccination with this bivalent vaccine
      primes T-helper cells that recognise common epitopes on SPA from an antigenically
      distinct B. canis isolate. These cells provide the essential Th signal to mount
      an effective and timely antibody response against SPA and parasites or
      parasitised erythrocytes, which prevents the further development of clinical
      babesiosis.

PMID- 11522409
TI  - An update on antileishmanial vaccine candidates and prospects for a canine
      Leishmania vaccine.
AB  - Dogs are the domestic reservoir for Leishmania infantum, the parasite causing
      zoonotic visceral leishmaniasis (VL) in both the Old and New Worlds. Since the
      available methods for canine leishmaniasis treatment and control have limited
      efficacy, the development of a canine Leishmania vaccine is highly desirable.
      Mechanisms of antileishmanial immune responses in murine, human, and canine
      infections are briefly presented. Vaccine candidates, including live or killed
      parasites, Leishmania purified fractions, defined recombinant parasite antigens,
      live recombinant bacteria expressing Leishmania antigens and antigen-encoding DNA
      plasmids, are reviewed. Finally, some practical requirements for the evaluation
      of vaccine candidates in dogs are indicated.

PMID- 11522410
TI  - Host responses against the fish parasitizing ciliate Ichthyophthirius
      multifiliis.
AB  - Recent studies have shown that fish are able to mount protective immune responses
      against various parasites. One of the best characterized parasite-host system in
      this context is the ciliate Ichthyophthirius multifiliis (Ich) parasitizing a
      range of freshwater fishes. Both specific and non-specific host defence
      mechanisms are responsible for the protection of fish against challenge
      infections with this ciliate. The specific humoral components comprise at least
      specific antibodies. The non-specific humoral elements included are the
      alternative complement pathway and probably lectins. Cellular factors involved in
      the specific response are B-cells and putative T-cells. The non-specific effector
      cells recognized are various leukocytes. In addition, goblet-cells and mast cells
      (EGC-cells) may have a function. The NCC-cell (suggested analogue to NK-cells in
      mammals) seems to play a role in the non-specific response. This well documented
      protective response in freshwater fishes against Ich has urged the development of
      anti-parasitic vaccines. Indeed, such products based on formalin killed parasites
      have been developed and found to offer the vaccinated host a satisfactory
      protection. However, the collection of parasites for vaccine production is
      extremely laborious. It involves keeping infected fish due to the fact that in
      vitro propagation of the parasite is still insufficiently developed. Gaining
      knowledge of amino acid sequences and its encoding DNA-sequences for the
      protective antigens (i-antigens) in the parasite was a major breakthrough. That
      achievement made it possible to produce a recombinant protein in E. coli and
      preliminary results indicated a certain protection of fish vaccinated with this
      product. Recent work has shown that the free-living and easily cultivated ciliate
      Tetrahymena can be transformed and express the i-antigen. This path seems to be
      promising for future development of vaccines against Ich. A novel approach in
      fish is the development of DNA-vaccines. Successful DNA-vaccination trials have
      been conducted in fish against viral infections and the technology also makes it
      possible to develop a DNA-vaccine against Ich. Other approaches to immuno
      protection against Ich have been the use of heterologous vaccines. Thus, both
      bath and injection vaccination using live or killed (un-transformed) Tetrahymena
      has been reported to offer treated fish a certain level of protection. Such
      protection could be explained by non-specific reactions and the efficacy and
      duration of this vaccination type should be further evaluated.

PMID- 11522411
TI  - Oncogenic osteomalacia associated with soft tissue chondromyxoid fibroma.
AB  - Oncogenic osteomalacia is a rarely described clinical entity characterized by
      hypophosphatemia, phosphaturia, and a low concentration of 1,25-dihydroxyvitamin
      D(3). It is most often associated with benign mesenchymal tumor and can be cured
      with surgical removal of the tumor. In this paper, we present a case of oncogenic
      osteomalacia caused by chondromyxoid fibroma in the soft tissue of the sole of
      the foot in a 56-year-old woman.

PMID- 11522412
TI  - MR imaging of nasopalatine duct cysts.
AB  - We describe the magnetic resonance (MR) features of two cases of nasopalatine
      duct cyst (NPDC), including the first presentation of T1-weighted images (WI).
      The signal intensity of the cases of NPDC showed homogeneous high signal
      intensity on both on T1 and T2WI, although most cysts of maxillofacial regions
      demonstrate low to intermediate signal intensity on T1WI. NPDC may commonly be of
      high signal intensity on T1WI, which is consistent with keratin and viscous
      fluids.

PMID- 11522413
TI  - The benign course of carotid-cavernous fistula in a child.
AB  - Carotid-cavernous fistulas (CCF) are reported very rarely in childhood and their
      clinical course and prognosis are uncertain. We report a 9-year-old boy presented
      with left eye swelling, neck pain and headache. The MRI findings suggested a CCF
      with enlarged left superior ophthalmic vein. Ocular Doppler ultrasonography
      revealed enlarged left superior ophthalmic vein, and arterialization of Doppler
      wave form. The cerebral angiogram showed normal anatomy. Control Doppler
      examination findings supported the diagnosis of closure of fistula. The clinical
      and radiological findings of this unusual presentation are discussed.

PMID- 11522414
TI  - Catheter-directed thrombolysis with transjugular access in portal vein thrombosis
      secondary to pancreatitis.
AB  - A case of portal vein thrombosis (PVT) secondary to pancreatitis is presented.
      Patient was treated with catheter-directed thrombolysis using urokinase solution.
      Because the percutaneous transhepatic approach is associated with higher risk of
      hemorrhage we used the catheter-directed thrombolysis via the transjugular
      intrahepatic access to restore the patency of the thrombosed portal vein. This
      case shows that catheter-directed thrombolysis with transjugular approach can be
      effectively used in the treatment of PVT.

PMID- 11522415
TI  - CT and MR imaging of localized amyloidosis.
AB  - The localized form of amyloidosis affecting the head and neck region is rare. The
      characteristic features of localized amyloidosis appeared as multiple nodules on
      the tongue, lip, and cheek on computed tomography (CT) and magnetic resonance
      imaging (MRI). Contrast-enhanced CT scans represented this lesion as a marked
      nodular enhancement. MR features of this lesion appeared slightly low on T1
      weighted images and slightly high on T2-weighted images compared with T1-T2
      images of residual normal tongue. Time contrast intensity curves obtained from
      dynamic MRI rapidly increased to reach a plateau and gradually decreased during
      the late and delayed phases. MR findings suggest that such lesions might be
      comprised of fibrous tissue with abundant vessels. This report suggests that
      dynamic MRI might be helpful for diagnosing localized amyloidosis.

PMID- 11522416
TI  - Magnetic resonance imaging characteristics of posterior scleritis mimicking
      choroidal mass.
AB  - We present imaging findings in a case of posterior scleritis, which may mimic
      tumoral mass lesion resulting in unnecessary enucleation. Magnetic resonance
      imaging was remarkable for a subretinal mass hypointense on T2 and hyperintense
      on T1 weighted images. A peripheral rim of hypointensity was noteworthy,
      suggestive of sclerouveal thickening. There was an ill-defined area of increased
      T2 signal intensity adjacent to globe at the site of nodular lesion implying an
      inflammatory process. A linear contrast enhancement was seen within the bulbus
      oculi which may represent detached retina by exudation or displaced retina due to
      thickened sclera and choroidal layers. The CSF space around the optic nerve was
      enlarged.

PMID- 11522417
TI  - Fat necrosis of the breast: clinical, mammographic and sonographic features.
AB  - OBJECTIVE: the purpose of this study was to describe and quantitate the clinical,
      mammographic and sonographic (US) features and to evaluate the evolution of fat
      necrosis in the breast. MATERIALS AND METHODS: a retrospective review of the
      clinical, mammographic and US findings of 126 fat necrosis lesions in 94
      patients, diagnosed between 1989 and 1999, was done. All the cases included in
      the study had at least 3 years follow-up mammograms. In addition, 48 patients
      with a total of 62 fat necrosis lesions, also had an US follow-up. Fat necrosis
      was diagnosed on the basis of histologic (n=25) and initial or follow-up imaging
      (n=69) findings. RESULTS: the predominant mammographic features of the 114
      lesions apparent on mammograms were radiolucent oil cyst (n=34, 26.9%), round
      opacity (n=16, 12.6%), asymmetrical opacity or heterogenicity of the subcutaneous
      tissues (n=20, 15.8%), dystrophic calcifications (n=34, 26.9%), clustered
      pleomorphic microcalcifications (n=5, 3.9%), and suspicious speculated mass (n=5,
      3.9%). In five patients with 12 (9.5%) palpable masses, mammograms were normal.
      The predominant US features of the 112 lesions apparent on sonograms were solid
      (n=18, 14.2%), anechoic with posterior acoustic enhancement (n=21, 16.6%),
      anechoic with posterior acoustic shadowing (n=20, 15.8%), cystic with internal
      echoes (n=14, 11.1%), cystic with mural nodule (n=5, 3.9%) and increased
      echogenicity of the subcutaneous tissues (n=34, 26.9%). In five patients with 14
      (11.1%) lesions, sonographic examination was normal. Mammographic follow-up
      showed that five of the radiolucent oil cysts developed curvilinear
      calcifications, six of the round opacities decreased in size and density, and
      another two disappeared. Eleven of the dystrophic calcifications became even more
      coarse. Six of the asymmetrical opacities became vague and one developed an oil
      cyst and coarse calcifications. The only nonoperated speculated mass developed a
      typical small radiolucent oil cyst in the centre. US follow-up showed that 18 of
      the 29 increased subcutaneous tissue echogenicity turned back to normal, while in
      the remaining 11 small cysts formed. In 19 solid appearing masses, 15 showed
      decrease in size, while four remained stable (biopsy disclosed fat necrosis). The
      four complex masses in two patients showed increase in size and appeared more
      cystic (FNAB was consistent with fat necrosis). CONCLUSION: a spectrum of imaging
      findings is associated with fat necrosis. Knowledge of the mammographic and US
      appearance and evolution of these patterns may enable imaging follow-up of these
      lesions, reducing the number of unnecessary biopsies.

PMID- 11522418
TI  - CT-guided preoperative needle localization of MRI-detected breast lesions.
AB  - To assess the value of accurate preoperative CT-guided needle localization of
      occult breast lesions, we reviewed a total of 39 needle-directed biopsies of
      breast tumors in 24 women. The average age was 52.9 years (range 31-67). All
      lesions were nonpalpable and mammographically, as well as sonographically occult.
      They were solely seen on MR-images. After demonstrating the suspicious region on
      CT scans, a hookwire was inserted. The correct position was confirmed by a
      control scan. The subsequent histopathological examination showed that 28 of the
      lesions (71.8%) were benign, among them mastopathy, fibrosis, fibroadenoma,
      papilloma, intramammary lymph node, liponecrosis and epitheliosis. Eleven lesions
      (28%) were malignant and showed either lobular, ductal or tubular cancer. Our
      results endorse that CT guided needle localization is a helpful method that
      allows a precise surgical excision of the suspect area with the removal of a
      minimal amount of breast tissue.

PMID- 11522419
TI  - Computed assisted detection of interval breast cancers.
AB  - OBJECTIVES: To examine interval cancer detection rate for a system of computer
      assisted detection (CAD) and its influence on radiologists'
      sensitivity/specificity in a screen-like retrospective review situation.
      MATERIALS AND METHODS: Three screening radiologists reviewed previous screen
      images of 59 interval cancers mixed with other screening mammograms (ratio 1:5)
      and non-mixed. Mixed interval cases were interpreted both without and with aid of
      CAD. RESULTS: CAD detected a number of 14 interval cancers while the three
      radiologists detected 17, 12 and 11 without and 16, 10 and 13 with CAD. Although
      CAD specificity was low (38%) no reduction in radiologists' specificity occurred
      using CAD (73%, 82% and 89% without and 78%, 90% and 92% with CAD). Non-mixed
      reading increased radiologists' detection rate to 21, 17 and 19 interval cancers
      respectively. CONCLUSION: Despite sufficiently high sensitivity for CAD alone no
      increase in radiologist sensitivity (or decrease in specificity) occurred with
      CAD. Improving CAD specificity, with unaffectedly high sensitivity, should make
      radiologists more inclined to revise interpretations according to CAD. The
      potential sensitivity increase, noted when using CAD as a double reader, could be
      realised in this way.

PMID- 11522420
TI  - Detection of lung cancer on the chest radiograph: a study on observer
      performance.
AB  - STUDY OBJECTIVES: to study the validity and observers consistency in the
      detection of lung cancer on the chest radiograph. MATERIALS AND METHODS: the
      chest radiographs of 100 clinical cases were interpreted by 14 observers. The
      radiographs were obtained from 30 patients with initially missed but
      histopathologically proven non-small cell lung cancer (NSCLC), 35 patients with
      other cardiopulmonary diseases and 35 patients with no abnormalities. The
      observers consisted of ten experienced radiologists, two-experienced chest
      physicians and two residents in radiology. All observers were unaware of the
      study design. The validity and observer consistency was determined for each
      observer. RESULTS: the mean sensitivity and specificity of the ten radiologists
      were 0.36 and 0.90. For the two chest physicians, the mean sensitivity and
      specificity were 0.29 and 0.96. For the two residents in radiology, mean
      sensitivity and specificity were 0.25 and 0.94. The mean interobserver kappa and
      mean intraobserver kappa for the radiologists were 0.38 and 0.54. For the two
      chest physicians, the mean interobserver kappa was 0.43, while the intraobserver
      kappa was 0.59. For the two residents in radiology, mean interobserver kappa was
      0.35 and the intraobserver kappa was 0.42. There was no significant relation
      between the consistency parameters and validity parameters. The interobserver and
      intraobserver kappa values showed good correlation. CONCLUSION: the validity of
      the chest radiograph and observers consistency in the detection of nodular lung
      cancer varies widely. The level of experience is likely to influence the
      diagnostic performance.

PMID- 11522421
TI  - MR imaging of meniscal cysts: evaluation of location and extension using a three
      layer approach.
AB  - PURPOSE: To analyze the extension of medial and lateral meniscal cysts relative
      to the capuloligamentous planes of the knee. MATERIALS AND METHODS: The MR images
      of 32 patients with meniscal cysts were reviewed. The location and extension of
      the meniscal cysts with reference to the capsule and ligaments were recorded.
      RESULTS: Most medial meniscal cysts were located posteromedially. Posteromedial
      meniscal cysts usually penetrated the capsule and were located between layer I
      and the fused layers II+III. From this site some extended anteriorly and then
      became located superficial to the superficial MCL. The location of lateral
      meniscal cysts was more varied. Anteriorly the cysts were located deep to the
      iliotibial band, whereas posterolateral cysts were located deep to the lateral
      collateral ligament. CONCLUSION: Although the site of capsular penetration of
      meniscal cysts is determined by the location of meniscal tears, the possible
      pathways of extension appear to be determined by the capsuloligamentous planes of
      the knee.

PMID- 11522422
TI  - Quiz case. Xanthogranulomatous pyelonephritis of the right kidney.

PMID- 11522424
TI  - Nicotinic receptor subtypes in human brain related to aging and dementia.
AB  - Neuronal nicotinic receptors are attracting increasing interest, beyond their
      role in relation to tobacco use, in the areas of human brain aging and disorders
      associated with dementia. Of the different receptor subtypes in the mammalian
      brain, many decline with normal aging in several different areas, including
      particularly cerebral cortex and hippocampus. There are further select subtype
      changes in the two most common forms of dementia in the elderly: Alzheimer's
      disease and dementia with Lewy bodies. The alpha4 subunit is most extensively
      reduced in the cortex in Alzheimer's disease, reflected in the loss of the high
      affinity binding site. There are also reductions in the low affinity binding site
      (alpha-bungarotoxin binding) in the thalamus in both disorders, which are likely
      to reflect the loss of the homomeric (most commonly alpha7) receptor subtype.
      Correlations exist between some of these receptor abnormalities and clinical and
      pathological features of the diseases. Targeting such receptors is a current
      therapeutic objective.

PMID- 11522426
TI  - Nicotinic acetylcholine receptors and neurodegenerative disease.
AB  - Nicotinic acetylcholine receptor (nAChR) in the central nervous system represents
      a new potential therapeutic target in neurodegenerative diseases, and this is
      driven by new findings in the molecular biology of nicotinic ion channel. Results
      of epidemiological studies have revealed that the incidence of Alzheimer's
      disease is lower among smokers compared with findings for nonsmokers, which seems
      to indicate that nicotine may influence cortical functions. We observed an
      increase in extracellular dopamine concentrations after administration of
      nicotine through a microdialysis tube. Nicotine might inhibit the uptake of
      dopamine through the nAChR, which could serve as a preventive factor against
      neurodegenerative diseases. We evaluated the ability of nicotine to protect
      neuronal cells from death by using the model system of serum- and nerve growth
      factor (NGF)-free cultures of PC12 cells. Serum and NGF deprivation induced rapid
      and massive death of these cells, which was inhibited by the addition of
      nicotine. These results suggest to us that nicotine may be involved in the
      protection of neuronal cells from death by means of nAChR. The effect of NGF and
      nicotine on the expression of nAChR subunits in PC12 cells was examined by using
      Northern blot analysis. Nerve growth factor increased the transcription of alpha5
      and beta4 subunits, whereas nicotine increased mRNA level encoding alpha5 and
      beta2 subunits. These results suggest to us that NGF changes the expression of
      nAChR in a subtype-specific manner over the course of differentiation, and
      disproportionate subunit expressions might be related to the neuroprotective
      effect exerted by nicotine.

PMID- 11522425
TI  - Potential regulation of nicotine and ethanol actions by alpha4-containing
      nicotinic receptors.
AB  - A restriction fragment length polymorphism (RFLP) associated with a major
      nicotinic receptor subunit (i.e., alpha4) has been identified in two mouse lines
      that were selectively bred for differences in sensitivity to ethanol. These mice,
      referred to as Long-Sleep (LS) and Short-Sleep (SS) mice, also differ in
      sensitivity to several effects of nicotine. The potential role of the alpha4 RFLP
      in regulating several responses to nicotine and ethanol was evaluated by using
      the LSxSS-derived recombinant inbred (RI) strains. Those RI strains that carried
      the LS-like alpha4 RFLP were more sensitive to the depressant effects of nicotine
      on Y-maze crossing and rearing activities and ethanol-induced increases in Y-maze
      crossing activity than were those RI strains that carry the SS-like alpha4 RFLP.
      The LS-like RI strains were also more sensitive to nicotine-induced hypothermia.
      The RFLP was not associated with strain differences in ethanol-induced body
      temperature or sleep time. The potential role of the RFLP in regulating ethanol
      and nicotine consumption was evaluated in heterogeneous stock (HS) mice. An
      association was found between the alpha4 RFLP and variation in ethanol
      consumption, but not in nicotine consumption, as measured in a four-bottle choice
      test. Recent studies of ethanol and tobacco abuse by human beings suggest that
      common genes may influence these two forms of substance abuse. The results of the
      studies reported here suggest that the alpha4 nicotinic receptor gene should be
      evaluated for its potential role in regulating ethanol and tobacco abuse in human
      beings.

PMID- 11522427
TI  - Nicotine and tobacco dependence: normalization or stimulation?
AB  - Nicotine and tobacco use produces mixed stimulant and depressant effects on
      various brain functions in animals and human beings. Results of
      electroencephalographic studies indicate that some tobacco smokers after 10-24 h
      of tobacco deprivation exhibit a decrease in dominant alpha rhythm, which,
      immediately after smoking, increases toward that of nonsmokers. This is evidence
      that tobacco smoking in smokers involves normalization of brain activity. Results
      of other studies of acute smoking effects in smokers show an increase in dominant
      alpha rhythm greater than that of nonsmokers. This is evidence that tobacco
      smoking produces stimulation of brain activity in smokers.

PMID- 11522428
TI  - Neurobiological mechanisms of nicotine craving.
AB  - Nicotine induces craving, but the degree of craving is believed to be milder than
      that with other abused drugs. In this article, the neurobiological mechanisms of
      craving for nicotine and other drugs are reviewed, focusing especially on three
      factors that can be involved in the development of craving. The first factor is
      the affective symptoms of withdrawal, the neural basis of which may involve
      neuroadaptations (desensitization) within the reward systems. Affective symptoms
      experienced during withdrawal from nicotine are milder than those experienced in
      withdrawal from other drugs, probably because of its mode of action on the reward
      systems, which is similar to that of natural rewards. The second factor is the
      conditioning process, in which environmental stimuli can gain properties of a
      secondary reinforcer. Nicotine has weak but reliable conditioning effects, and
      the brain region mediating those effects of nicotine involves the ventral
      tegmental area. The third factor is a cognitive (memory) process, but little is
      known about this area.

PMID- 11522429
TI  - Electroencephalographic characterization of cigarette smoking behavior.
AB  - The rewarding properties of used and abused substances are related to their
      ability to modulate central processes subserving mood, cognition, and behavior.
      Research into the motivationally relevant factors mediating substance use and
      abuse among human beings, including tobacco smoking, can strategically benefit
      from the utilization of noninvasive brain function measures that are able to
      probe the neurobiology of brain states in concert with substance ingestion. This
      paper reviews investigations from my laboratory with the use of neuroelectric
      tools, by means of quantitative electroencephalography, for the purpose of
      characterizing the central response to cigarette smoking. Prominent in these
      strategies is the acute smoking paradigm, whereby measures are focused on the
      profiling of central responsivity to smoke inhalation from a single cigarette and
      administration of test doses of nicotine. Complementing this approach are studies
      (1) in which receptor antagonists are administered in an attempt to explore
      putative transmitter systems regulating the acute smoking-induced
      electroencephalographic response and (2) in which electroencephalographic
      profiles of acute smoking are compared with electroencephalographic profiles
      resulting from administration of single doses of psychotropic substances.
      Completing these studies are attempts to monitor the electrocortical correlates
      of repeated smoking exposure and smoking deprivation, which, together with
      investigations examining smoker vs. nonsmoker differences and the effects of
      chronic life-long smoking, provide objective insights into the
      neuroelectrophysiology underlying the smoking habit.

PMID- 11522430
TI  - Nicotine, alcohol, methamphetamine, and inhalant dependence: a comparison of
      clinical features with the use of a new clinical evaluation form.
AB  - The purpose of the present study was to develop a new clinical evaluation form to
      compare the clinical features of nicotine dependence with those associated with
      alcohol, methamphetamine, and inhalant dependence. The clinical evaluation form
      consisted of six scoring items: subjective effects, tolerance, liking (of drug),
      social disturbance, withdrawal syndrome, and acute psychic and acute physical
      disorders. A preliminary clinical investigation was performed to test the
      validity of the evaluation form. Study subjects were those showing dependence on
      nicotine (n = 25), alcohol (n = 36), methamphetamine (n = 11), and inhalants (n =
      6). All subjects met the Diagnostic and Statistical Manual of Mental Disorders
      (4th ed.) diagnostic criteria for drug dependence, as defined by the Work Group
      for the chapter "Substance-Related Disorders": M. A. Schuckit, J. E. Helzer, L.
      B. Cottler, T. Crowley, P. E. Nathan, & G. E. Woody. Nicotine produced subjective
      effects, tolerance, liking, and psychic withdrawal symptoms, all of which were
      mild in degree. However, nicotine did not produce social disturbance, physical
      withdrawal symptoms, or acute psychic or acute physical disorders. With alcohol,
      acute psychic and acute physical disorders were prominent, and alcohol also
      produced a moderate degree of influence on various other items that were
      evaluated. Methamphetamine produced the most serious acute psychic and acute
      physical disorders with intensive subjective effects. Inhalants were
      characterized by an intensive degree of acute psychic disorders and subjective
      effects with mild withdrawal syndrome. Our study findings revealed that the
      clinical features of drug dependence could be evaluated by using the new clinical
      evaluation form. Further study is required to clarify the clinical features of
      nicotine dependence compared with those of other drugs of dependence.

PMID- 11522431
TI  - Epidemiological studies of tobacco smoking and dependence in Japan.
AB  - In this study, we attempted to determine the prevalence of tobacco or nicotine
      dependence in current smokers in Japan and to assess the relationship between
      alcoholism and tobacco or nicotine dependence. The subjects consisted of 246
      alcohol-dependent and 1,111 non-alcohol-dependent individuals. We used a
      questionnaire, consisting of items obtained from the World Health Organization's
      The ICD-10 Classification of Mental and Behavioural Disorders: Clinical
      Descriptions and Diagnostic Guidelines (ICD-10) and the American Psychiatric
      Association's Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM
      IV) criteria for tobacco or nicotine dependence. The prevalence of tobacco
      dependence diagnosed according to the ICD-10 criteria was 23.9% among all
      subjects. The prevalence of tobacco dependence diagnosed according to the ICD-10
      criteria was higher in alcohol-dependent individuals (58.1%) than in nondrinkers
      or social drinkers (12.8%). Alcohol-dependent subjects consumed significantly
      more nicotine per day than did nondrinkers or social drinkers. The prevalence of
      nicotine physical dependence diagnosed by using DSM-IV criteria for nicotine
      withdrawal was 2.4% in alcohol-dependent individuals, whereas only 0.3% of
      nondrinkers or social drinkers exhibited nicotine physical dependence. These
      results indicate to us that the potential for nicotine physical dependence is not
      much stronger than that reported among current smokers.

PMID- 11522432
TI  - Relapse prevention in alcoholics by cigarette smoking? Involvement of nicotinic
      dopaminergic mechanisms.
AB  - Because of a controversial view on the role of smoking in the recovery process of
      alcoholism, outcome data obtained for alcoholics who had been included in a long
      term clinical trial with a putative anticraving drug were analyzed. To avoid
      unknown interactions between the drug under study and smoking behavior, only
      placebo-treated patients were evaluated in this investigation. After 12 months of
      rehabilitation, there was no significant difference regarding abstinence rate
      between 48 smoking alcoholics (who reported that they smoked 32 cigarettes on
      average per day) and 15 nonsmoking alcoholics (33% vs. 20%). However, smokers
      tended to be abstinent longer than nonsmokers (173 vs. 114 days; P= .092). This
      possible advantage might be related to nicotinic effects on central dopamine
      systems in smokers, as indicated by higher growth hormone secretion after
      apomorphine stimulation obtained in smokers, compared with findings for
      nonsmokers (area under the curve during chronic intoxication: 2253 vs. 1247
      microg/min/l; P= .019). Multivariate regression analysis revealed a decreasing
      effect of ethanol blood level (P= .006) and the number of fullfilled
      International Classification of Diseases, 10th edition (ICD-10) criteria of the
      alcohol dependence syndrome (P= .012) on stimulated growth hormone secretion. In
      contrast, the reported number of smoked cigarettes per day had an increasing
      effect (P= .034), accounting for 6% of the variance of growth hormone secretion.
      However, differences in outcome could also be explained by other clinical
      features as smokers, compared with nonsmokers, were more frequently males (78.3%
      vs. 60.7%) and younger when studied at index episode (mean age 44.45 vs. 48.21
      years; P= .054), reported higher ethanol consumption in the month before hospital
      admission (262 g vs. 192 g; P= .044), and met more criteria for the ICD-10
      alcohol dependence syndrome (6.6 vs. 6.0; P= .047). Therefore, it cannot be
      stringently inferred from our data that a possible advantage of smoking for
      alcoholism recovery is causally related to the effects of nicotine on cerebral
      systems or human behavior, as our findings had not been based on a randomized
      design.

PMID- 11522433
TI  - Oral drug self-administration: an overview of laboratory animal studies.
AB  - Many abused drugs can be established as orally delivered reinforcers for rhesus
      monkeys and other animals. Benzodiazepines, barbiturates, opioids, psychomotor
      stimulants, dissociative anesthetics, and ethanol can come to serve as
      reinforcers when taken by mouth. The principal problems in establishing drugs as
      reinforcers by the oral route of administration are (1) aversive taste, (2) delay
      in onset of central nervous system effects, and (3) consumption of low volumes of
      drug solution. Strategies have been devised to successfully overcome these
      problems, and orally delivered drugs can be established as effective reinforcers.
      Reinforcing actions are demonstrated by consumption of greater volumes of drug
      solution than volumes of the water vehicle, and supporting evidence for
      reinforcing effects consists of the maintenance of behavior under intermittent
      schedules of reinforcement and the generation of orderly dose-response functions.
      This article presents an overview of studies of behavior reinforced by oral drug
      reinforcement. Factors that control oral drug intake include dose, schedule of
      reinforcement, food restriction, and alternative reinforcers. Many drugs,
      administered by the experimenter, can alter oral drug reinforcement. Relative
      reinforcing effects can be assessed by choice procedures and by persistence of
      behavior across increases in schedule size. In general, reinforcing effects
      increase directly with dose. Rhesus monkeys prefer combinations of reinforcing
      drugs to the component drugs. The taste of drug solutions may act as a
      conditioned reinforcer and a discriminative stimulus. Consequences of drug intake
      include tolerance and physiological dependence. Findings with orally self
      administered drugs are similar to many findings with other positive reinforcers,
      including intravenously self-administered drugs.

PMID- 11522434
TI  - Genetic analysis of the mu-opioid receptor in alcohol-dependent individuals.
AB  - On the basis of various study results, it is suggested that the ethanol-induced
      activation of the endogenous opioid system may play an important role in
      mediating the reinforcing effects of ethanol. The mesolimbic dopamine reward
      system is activated by both ethanol and opioids, and genetic differences in the
      sensitivity of the endogenous opioid system to alcohol may be an important factor
      determining the risk for the development of excessive alcohol consumption. Thus,
      variants of the mu-opioid receptor (muOR) gene may confer vulnerability to
      alcohol dependence. Five exon 1 variants of the muOR were investigated in 327
      alcohol-dependent and 340 healthy control subjects. The Val6 variant of the
      +17C/T polymorphism and the Asp40 variant of the +118A/G polymorphism showed a
      trend to an increased allele frequency in alcohol-dependent subjects. The latter
      polymorphism was investigated in more detail. The dopamine receptor agonist
      apomorphine causes an increase in growth hormone (GH) levels in the blood by
      stimulating the release of growth hormone-releasing hormone. beta-endorphin also
      activates this regulatory circuit. We found a blunted response in intoxicated
      alcohol-dependent subjects, but no difference in GH response between the groups
      of alcohol-dependent subjects with and without the variant Asp allele. However,
      alcohol-dependent subjects with the Asp allele showed a significantly higher GH
      response at day 7 after alcohol withdrawal and a tendency to lower novelty
      seeking. These results suggest to us that there is reduced dopaminergic neuronal
      activity in alcohol-dependent subjects with the muOR Asp40 allele, along with a
      compensating increase in dopamine receptor activity. The difference between the
      two groups of alcohol-dependent subjects can be demonstrated only under certain
      conditions such as alcohol withdrawal, which necessitates the adaptation of the
      neurones to a new homeostasis.

PMID- 11522435
TI  - Ethanol-related adaptive changes and physical dependence in rats after exposure
      to ethanol.
AB  - Adaptive changes that occur after chronic exposure to ethanol are an important
      component in the development of physical dependence. We have focused our research
      on ethanol-induced changes in the expression of several genes that may be
      important in adaptation. In this article, we describe adaptive changes at the
      level of the N-methyl-D-aspartate receptor, in the protein expression and
      activity of the Egr transcription factors, and in the expression of a novel gene
      of unknown function.

PMID- 11522436
TI  - Distribution of calbindin, parvalbumin and calretinin in the lateral geniculate
      nucleus and superior colliculus in Cebus apella monkeys.
AB  - We studied the distribution of the calcium-binding proteins calbindin,
      parvalbumin and calretinin, in the superior colliculus and in the lateral
      geniculate nucleus of Cebus apella, a diurnal New World monkey. In the superior
      colliculus, these calcium-binding proteins show different distribution patterns
      throughout the layers. After reaction for calretinin one observes a heavy
      staining of the neuropil with few labeled cells in superficial layers, a greater
      number of large and medium-sized cells in the stratum griseum intermediale, and
      small neurons in deep layers. The reaction for calbindin revealed a strong
      staining of neuropil with a large number of small and well stained cells, mainly
      in the upper half of the stratum griseum superficiale. Intermediate layers were
      more weakly stained and depicted few neurons. There were few immunopositive cells
      and little neuropil staining in deep layers. The reaction for parvalbumin showed
      small and medium-sized neurons in the superficial layers, a predominance of large
      stellate cells in the stratum griseum intermediale, and medium-sized cells in the
      deep layers. In the lateral geniculate nucleus of Cebus, parvalbumin is found in
      the cells of both the P and M pathways, whereas calbindin is mainly found in the
      interlaminar and S layers, which are part of the third visual pathway. Calretinin
      was only found in cells located in layer S. This pattern is similar to that
      observed in Macaca, showing that these calcium-binding proteins reveal different
      components of the parallel visual pathways both in New and Old World monkeys.

PMID- 11522437
TI  - Presence of neuronal nitric oxide synthase in autonomic and sensory ganglion
      neurons innervating the lacrimal glands of the cat: an immunofluorescent and
      retrograde tracer double-labeling study.
AB  - It is generally considered that parasympathetic postganglionic nerve fibers
      innervating the lacrimal gland (LG) arise from the pterygopalatine ganglion
      (PPG), while sympathetic and sensory innervations arise from the superior
      cervical ganglion (SCG) and trigeminal ganglion (TG), respectively. Recently, we
      reported for the first time that the parasympathetic innervation of the cat LG
      was also provided by the otic ganglion (OG) and ciliary ganglion (CG), and that
      the sensory innervation was also provided by the superior vagal ganglion (SVG)
      and superior glossopharyngeal ganglion (SGG). To determine if nitric oxide (NO)
      is a neurotransmitter of the autonomic and sensory neurons innervating the LG, we
      injected the cholera toxin B subunit (CTB) as a retrograde tracer into the cat
      LG, and used double-labeling fluorescent immunohistochemistry for CTB and nitric
      oxide synthase (NOS). We found that NOS-/CTB-immunofluorescent double-labeled
      perikarya were localized in the PPG, OG, TG, SVG and SGG, but not in the CG and
      SCG. The highest numbers of NOS-/CTB-immunofluorescent double-labeled neurons
      were found in the PPG and TG. In addition, we examined the presence of nitrergic
      nerve fibers in the LG using NADPH-d histochemistry and found that a large amount
      of NADPH-d-stained nerve fibers were distributed around the glandular acini and
      in the walls of glandular ducts and blood vessels. This study provides the first
      direct evidence showing that NO may act as a neurotransmitter or modulator
      involved in the parasympathetic and sensory regulation of lacrimal secretion and
      blood circulation, but may not be implicated in the sympathetic control of LG
      activities, and that nitrergic nerve fibers in the LG arise mainly from
      parasympathetic postganglionic neurons in the PPG and sensory neurons in the TG.
      The present results suggest that NO plays an important role in the regulation of
      LG activities.

PMID- 11522438
TI  - Alpha(1B) receptors are the main postsynaptic mediators of adrenergic excitation
      in brainstem motoneurons, a single-cell RT-PCR study.
AB  - Norepinephrine (NE) is an important modulator of brainstem motoneurons. It is
      released at high levels during wakefulness, whereas its reduced release during
      sleep may contribute to motor suppression, including upper airway hypotonia. To
      identify the receptors that mediate postsynaptic effects of NE in brainstem
      motoneurons of juvenile and adult rats, we determined the pattern of adrenoceptor
      mRNA expression and co-expression in retrogradely labeled and acutely dissociated
      hypoglossal (XII) motoneurons (n=121) using single-cell, real-time reverse
      transcription-polymerase chain reaction (RT-PCR). The alpha(1B) receptor mRNA was
      present in most motoneurons (33/39 or 85%). The remaining six adrenoceptor mRNA
      species investigated were consistently present in micropunches of tissue
      extracted from the XII nucleus, but were either rarely expressed in individual
      motoneurons (alpha(1A) mRNA in 15%, alpha(1D) in 14%, alpha(2B/C) in 2% of cells)
      or absent (alpha(2A), beta(1) and beta(2)). When present, the alpha(1A) and
      alpha(1D) mRNAs were co-expressed with alpha(1B) mRNA. The adrenoceptor mRNA
      expression profiles in dissociated locus coeruleus and inferior olive neurons
      were significantly different. We conclude that postsynaptic effects of NE in XII
      motoneurons are primarily mediated by alpha(1B) receptors; the effects ascribed
      to alpha(2) and/or beta adrenoceptors may be exerted presynaptically.

PMID- 11522439
TI  - Nitric oxide synthase-I containing cortical interneurons co-express antioxidative
      enzymes and anti-apoptotic Bcl-2 following focal ischemia: evidence for direct
      and indirect mechanisms towards their resistance to neuropathology.
AB  - Neuronal nitric oxide-I is constitutively expressed in approximately 2% of
      cortical interneurons and is co-localized with gamma-amino butric acid,
      somatostatin or neuropeptide Y. These interneurons additionally express high
      amounts of glutamate receptors which mediate the glutamate-induced
      hyperexcitation following cerebral injury, under these conditions nitric oxide
      production increases contributing to a potentiation of oxidative stress. However,
      perilesional nitric oxide synthase-I containing neurons are known to be resistant
      to ischemic and excitotoxic injury. In vitro studies show that nitrosonium and
      nitroxyl ions inactivate N-methyl-D-aspartate receptors, resulting in
      neuroprotection. The question remains of how these cells are protected against
      their own high intracellular nitric oxide production after activation. In this
      study, we investigated immunocytochemically nitric oxide synthase-I containing
      cortical neurons in rats after unilateral, cortical photothrombosis. In this
      model of focal ischemia, perilesional, constitutively nitric oxide synthase-I
      containing neurons survived and co-expressed antioxidative enzymes, such as
      manganese- and copper-zinc-dependent superoxide dismutases, heme oxygenase-2 and
      cytosolic glutathione peroxidase. This enhanced antioxidant expression was
      accompanied by a strong perinuclear presence of the antiapoptotic Bcl-2 protein.
      No colocalization was detectable with upregulated heme oxygenase-1 in glia and
      the superoxide and prostaglandin G(2)-producing cyclooxygenase-2 in neurons.
      These results suggest that nitric oxide synthase-I containing interneurons are
      protected against intracellular oxidative damage and apoptosis by Bcl-2 and
      several potent antioxidative enzymes. Since nitric oxide synthase-I positive
      neurons do not express superoxide-producing enzymes such as cyclooxygenase-1,
      xanthine oxidase and cyclooxygenase-2 in response to injury, this may
      additionally contribute to their resistance by reducing their internal
      peroxynitrite, H(2)O(2)-formation and caspase activation.

PMID- 11522440
TI  - Relationships of 5-hydroxytryptamine immunoreactive terminal-like varicosities to
      5-hydroxytryptamine-2A receptor-immunoreactive neuronal processes in the rat
      forebrain.
AB  - The distributions of 5-hydroxytryptamine (5-HT)-immunoreactive (IR) varicosities
      and 5-hydroxytryptamine-2A receptor (5-HT2A)-IR neuronal structures in the rat
      brain have previously been described individually. Using double labeling
      immunocytochemistry, the relationships between 5-HT2A-IR and 5-HT-IR elements in
      the forebrain of male rats has been studied at the light microscopic level. In
      neocortical regions (frontal, parietal and retrosplenial cortex), the strongest 5
      HT2A-IR was found in the apical dendrites of pyramidal cells in layers III-V,
      while 5-HT-IR terminal-like varicosities were present in all layers but most
      prominently in the outer layers. In other forebrain regions, the olfactory bulb,
      the hippocampal formation, and the islands of Calleja and Calleja magna,
      localized discrepancies were present between the 5-HT2A-IR neuronal profiles and
      the 5-HT-IR terminal-like varicosities. Hardly any additional juxtapositions
      between the 5-HT2A-IR neuronal profiles and 5-HT-IR terminal-like varicosities
      were revealed when the intraneuronal level of 5-HT was increased by monoamine
      oxidase inhibitor pretreatment (nialamide, 250 mg/kg, 3 h). Thus, in most
      forebrain regions, there were overall few juxtapositions between 5-HT terminal
      like varicosities and 5-HT2A-IR neuronal structures. This observation suggests
      that 5-HT2A receptor mediated 5-HT transmission in the rat forebrain is mainly a
      volume transmission process mediated via short distance diffusion in the extra
      cellular space.

PMID- 11522441
TI  - Neuroprotective adaptations in hibernation: therapeutic implications for ischemia
      reperfusion, traumatic brain injury and neurodegenerative diseases.
AB  - Brains of hibernating mammals are protected against a variety of insults that are
      detrimental to humans and other nonhibernating species. Such protection is
      associated with a number of physiological adaptations including hypothermia,
      increased antioxidant defense, metabolic arrest, leukocytopenia,
      immunosuppression, and hypocoagulation. It is intriguing that similar
      manipulations provide considerable protection as experimental treatments for
      central nervous system injury. This review focuses on neuroprotective mechanisms
      employed during hibernation that may offer novel approaches in the treatment of
      stroke, traumatic brain injury, and neurodegenerative diseases in humans.

PMID- 11522442
TI  - Proteasomes and proteasome inhibition in the central nervous system.
AB  - Although the proteasome is responsible for the majority of intracellular protein
      degradation, and has been demonstrated to play a pivotal role in a diverse array
      of cellular activities, the role of the proteasome in the central nervous system
      is only beginning to be elucidated. Recent studies have demonstrated that
      proteasome inhibition occurs in numerous neurodegenerative conditions, and that
      proteasome inhibition is sufficient to induce neuron death, elevate intracellular
      levels of protein oxidation, and increase neural vulnerability to subsequent
      injury. The focus of this review is to describe what is currently known about
      proteasome biology in the central nervous system and to discuss the possible role
      of proteasome inhibition in the neurodegenerative process.

PMID- 11522443
TI  - Induction of thioredoxin by ultraviolet-A radiation prevents oxidative-mediated
      cell death in human skin fibroblasts.
AB  - The present study analyzes the expression of the thioredoxin/thioredoxin
      reductase (Trx/TR) system in UVA-irradiated human skin fibroblasts. Irradiation
      increases the intracellular level of Trx and a time-dependent increase of Trx
      mRNA is observed. Our data indicate that Trx translocates from the cytoplasm to
      the nucleus. In addition, UV exposure results in an increase in TR synthesis. In
      order to evaluate the function of Trx/TR system, we investigated the antioxidant
      role of Trx in transient transfected cells. The ROS accumulation in UVA
      irradiated cells was assessed using flow cytometry. A 3-fold decrease in ROS
      production was observed in transiently transfected fibroblasts. These results
      indicate that Trx acts as an antioxidant protein in UVA irradiated fibroblasts.
      As ROS are inducers of cell death, this raises the question as to whether Trx is
      able to protect cells from apoptosis and/or necrosis induced by UVA. Six hours
      after UVA-irradiation, 29.92% of cells were annexin-V positive. This population
      was significantly reduced in Trx-transfected cells (8.58%). Moreover, this work
      demonstrates that Trx prevents the loss of the membrane potential of the
      mitochondria, the depletion of cellular ATP content, and the loss of cell
      viability induced by irradiation.

PMID- 11522444
TI  - Synthesis and biochemical applications of a solid cyclic nitrone spin trap: a
      relatively superior trap for detecting superoxide anions and glutathiyl radicals.
AB  - A novel cyclic nitrone spin trap, 5-tert-butoxycarbonyl 5-methyl-1-pyrroline N
      oxide (BMPO) as a pure white solid has been synthesized for the first time. BMPO
      offers several advantages over the existing spin traps in the detection and
      characterization of thiyl radicals, hydroxyl radicals, and superoxide anions in
      biological systems. The corresponding BMPO adducts exhibit distinct and
      characteristic electron spin resonance (ESR) spectral patterns. Unlike the 5,5
      dimethyl-1-pyrroline N-oxide (DMPO)-derived superoxide adduct, the BMPO
      superoxide adduct does not non-enzymatically decompose to the BMPO hydroxyl
      adduct. This feature is clearly perceived as a definite advantage of BMPO in its
      biological applications. In addition, the ESR spectrum of the BMPO glutathionyl
      adduct (BMPO/*SG) does not fully overlap with the spectrum of its hydroxyl
      adduct. This spectral feature is again distinctly different from that of DMPO
      because the ESR spectral lines of DMPO glutathionyl and hydroxyl radical adducts
      largely overlap. Finally, the ESR spectra of BMPO-derived adducts exhibit a much
      higher signal-to-noise ratio in biological systems. These favorable chemical and
      spectroscopic features make BMPO ideal for the detection of superoxide anions,
      hydroxyl and thiyl radicals in biochemical oxidation and reduction.

PMID- 11522445
TI  - Nicorandil decreases postischemic actin oxidation.
AB  - This study examined the hypothesis that preconditioning can decrease postischemic
      oxidative protein damage. Isolated rat hearts were subjected to 25 min of
      normothermic global ischemia followed by 45 min of reperfusion. These were
      compared with hearts pretreated with 20 microM nicorandil or preconditioned with
      two cycles of ischemia. Changes in the high energy phosphates, ATP and
      phosphocreatine, were followed using (31)P-NMR spectroscopy. Protein carbonyls
      were assessed using an immunoblot technique. Postischemic hemodynamic function
      and high energy phosphates recovered to significantly (p <.05) higher levels in
      nicorandil-treated and ischemic preconditioned hearts as compared to controls.
      Postischemic protein carbonyl formation was highest in control reperfused hearts
      but reduced to intermediate between control and preischemic hearts by ischemic
      preconditioning and virtually prevented by nicorandil pretreatment, with a
      prominent band at 43 kDa significantly affected (p <.05). Based on immunoshift
      and immunoprecipitation studies, this band was identified as a mixture of actin
      isoforms. These studies support the conclusion that nicorandil diminishes protein
      oxidative damage in general, and specifically actin oxidation, which in the
      presence of improved supply of high energy phosphates, leads to enhanced
      postischemic contractile function.

PMID- 11522446
TI  - Puromycin aminonucleoside induces apoptosis and increases HNE in cultured
      glomerular epithelial cells(1).
AB  - Puromycin aminonucleoside induces apoptosis and increases 4-hydroxy-2-nonenal
      (HNE) in cultured glomerular epithelial cells. We have previously reported the
      detachment of cultured glomerular epithelial cells (GECs) from their substrata by
      puromycin aminonucleoside (PAN) treatment. In this study we explored whether or
      not apoptosis was involved in the mechanisms of the detachment. DNA fragmentation
      on gel electrophoresis was clearly shown by 10(-3) M PAN treatment of GECs.
      Nuclear staining by Hoechst 33342 indicated the greatest number of apoptotic
      cells at 10(-3) M PAN for 48 h treatment. Similarly, TUNEL methods revealed
      maximal apoptotic cells at 10(-3) M PAN for 48 h treatment. Caspase-3 (like)
      protease activity increased at 10(-3) M PAN, and decreased at 2 x 10(-3) M PAN
      for 48 h treatment as well as at 10(-3) M PAN for 60 h treatment. Pretreatment
      with 2'-deoxycoformycin (DCF), inhibitor of adenosine deaminase, abolished these
      effects of PAN on cultured GECs. PAN treatment increased HNE, a lipid peroxide
      adduct, modified protein in cultured GECs, which was also prevented by
      pretreatment by DCF. These results for the first time indicate that the PAN
      induced detachment of GECs from culture substrata is mediated at least in part
      through apoptosis via oxidative stresses by adenosine deaminase activity.

PMID- 11522447
TI  - The hydrogen peroxide/copper ion system, but not other metal-catalyzed oxidation
      systems, produces protein-bound dityrosine.
AB  - Dityrosine formation leads to the cross-linking of proteins intra- or
      intermolecularly. The formation of dityrosine in lens proteins oxidized by metal
      catalyzed oxidation (MCO) systems was estimated by chemical and immunochemical
      methods. Among the four MCO systems examined (H(2)O(2)/Cu, H(2)O(2)/Fe
      ethylenediaminetetraacetic acid (Fe-EDTA), ascorbate/Cu, ascorbate/Fe-EDTA), the
      treatment with H(2)O(2)/Cu preferentially caused dityrosine formation in the lens
      proteins. The success of oxidative protein modification with all the MCO systems
      was confirmed by carbonyl formation estimated using 2,4-dinitrophenylhydrazine.
      The loss of tyrosine by the MCO systems was partly due to the formation of
      protein-bound 3,4-dihydroxyphenylalanine. The formation of dityrosine specific to
      H(2)O(2)/Cu was confirmed by using poly-(Glu, Ala, Tyr) and N-acetyl-tyrosine as
      a substrate. The dissolved oxygen concentration in the H(2)O(2)/Cu system hardly
      affected the amount of dityrosine formation, suggesting that dityrosine
      generation by the H(2)O(2)/Cu system is independent of oxygen concentration.
      Moreover, the combination of copper ion with H(2)O(2) is the most effective
      system for dityrosine formation among various metal ions examined. The addition
      of reducing agents, glutathione or ascorbic acid, into the H(2)O(2)/Cu system
      suppressed the generation of the dityrosine moiety, suggesting effective quench
      of tyrosyl radicals by the reducing agents.

PMID- 11522448
TI  - Impaired accumulation of granulocytes in the lung during ozone adaptation.
AB  - Respiratory alterations induced by an acute exposure to ozone (O(3))
      paradoxically resolve during multiday exposure. This adaptation is
      characteristically accompanied by a gradual attenuation of lung neutrophilia. As
      maintenance of neutrophilia at the site of inflammation is due to cytokine
      mediated delayed neutrophil apoptosis, which is associated with reduced levels of
      Bax, a proapoptotic protein, we sought to determine whether defects in these
      mechanisms could account for O(3) adaptation. Lung granulocytes obtained at
      different time points from calves exposed to 0.75 ppm O(3) for 12 h/d for 7
      consecutive days neither showed enhancement of survival nor Bax deficiency, when
      compared to blood granulocytes. To further investigate the effects of an
      exogenous oxidative stress on neutrophil survival, human granulocytes were
      treated with hydrogen peroxide alone, or in combination with
      granulocyte/macrophage colony-stimulating factor, an antiapoptotic cytokine. Both
      treatments led to rapid apoptosis associated with downregulation of Bcl-x(L) and
      Bcl-2, two antiapoptotic proteins. This study shows that O(3) adaptation is
      associated with a failure in the mechanisms leading to accumulation of
      neutrophils at the site of inflammation, and suggests that this defect is due to
      direct proapoptotic effects of exogenous oxidative stress on granulocytes.

PMID- 11522450
TI  - H(2)O(2)-mediated oxidative stress activates NF-kappa B in lens epithelial cells.
AB  - In the mammalian lens, intracellular oxidants produced by photo-oxidative
      processes and exposure to toxic chemicals constitute stresses that produce
      cellular oxidative damage, result in changes in gene expression, and are causally
      related to cataract formation. Currently, it is believed that H(2)O(2) is the
      major oxidant to which the lens is exposed. In this report, we examine the
      activation and regulation of the oxidant-sensitive transcription factor, NF-kappa
      B, by H(2)O(2)-mediated oxidative stress in lens epithelial cells. Lens
      epithelial cells treated with H(2)O(2) demonstrated at 1 h a strong activation of
      NF-kappa B which returned to basal levels by 2 h. Under proteasome inhibition
      using both MG132 and lactacystin, H(2)O(2)-mediated activation of NF-kappa B was
      prevented, implicating the involvement of proteasome degradation of I kappa B
      proteins as being necessary for this activation. However, Western blot analysis
      demonstrated no degradation of I kappa B-alpha, -beta, or -epsilon associated
      with H(2)O(2)-mediated NF-kappa B activation. In comparison, when cells were
      treated with the cytokine TNF-alpha, NF-kappa B was strongly activated and
      degradation of both I kappa B-alpha and -beta was observed. These results clearly
      demonstrate that H(2)O(2)-mediated oxidative stress activates NF-kappa B in lens
      epithelial cells, which may subsequently lead to changes in gene expression. The
      results also reveal that different signaling pathways in the activation of NF
      kappa B in lens epithelial cells are utilized by H(2)O(2) and TNF-alpha. These
      different pathways of NF-kappa B activation may be required to effect specific NF
      kappa B-dependent gene expression in response to these different stimuli.

PMID- 11522449
TI  - Glutamine potentiates TNF-alpha-induced tumor cytotoxicity.
AB  - L-glutamine (Gln) sensitizes tumor cells to tumor necrosis factor (TNF)-alpha
      induced cytotoxicity. The type and mechanism of cell death induced by TNF-alpha
      was studied in Ehrlich ascites tumor (EAT)-bearing mice fed a Gln-enriched diet
      (GED; where 30% of the total dietary nitrogen was from Gln). A high rate of Gln
      oxidation promotes a selective depletion of mitochondrial glutathione (mtGSH)
      content to approximately 58% of the level found in tumor mitochondria of mice fed
      a nutritionally complete elemental diet (standard diet, SD). The mechanism of
      mtGSH depletion involves a glutamate-induced inhibition of GSH transport from the
      cytosol into mitochondria. The increase in reactive oxygen intermediates (ROIs)
      production induced by TNF-alpha further depletes mtGSH to approximately 35% of
      control values, which associates with a decrease in the mitochondrial
      transmembrane potential (MMP), and elicits mitochondrial membrane
      permeabilization and release of cytochrome c. Mitochondrial membrane
      permeabilization was also found in intact tumor cells cultured with a Gln
      enriched medium under conditions of buthionine sulfoximine (BSO)-induced
      selective GSH synthesis inhibition. Enforced expression of the bcl-2 gene in
      tumor cells could not avoid the glutamine- and TNF-alpha-induced cell death under
      conditions of mtGSH depletion. However, addition of GSH ester, which delivers
      free intracellular GSH and increases mtGSH levels, preserved cell viability.
      These findings show that glutamine oxidation and TNF-alpha, by causing a change
      in the glutathione redox status within tumor mitochondria, activates the
      molecular mechanism of apoptotic cell death.

PMID- 11522451
TI  - Mechanism of clofibrate hepatotoxicity: mitochondrial damage and oxidative stress
      in hepatocytes.
AB  - Peroxisome proliferators have been found to induce hepatocarcinogenesis in
      rodents, and may cause mitochondrial damage. Consistent with this, clofibrate
      increased hepatic mitochondrial oxidative DNA and protein damage in mice. The
      present investigation aimed to study the mechanism by which this might occur by
      examining the effect of clofibrate on freshly isolated mouse liver mitochondria
      and a cultured hepatocyte cell line, AML-12. Mitochondrial membrane potential
      (Delta Psi(m)) was determined by using the fluorescent dye 5,5',6,6'-tetrachloro
      1,1', 3,3'-tetraethyl-benzimidazolylcarbocyanine iodide (JC-1) and
      tetramethylrhodamine methyl ester (TMRM). Application of clofibrate at
      concentrations greater than 0.3 mM rapidly collapsed the Delta Psi(m) both in
      liver cells and in isolated mitochondria. The loss of Delta Psi(m) occurred prior
      to cell death and appeared to involve the mitochondrial permeability transition
      (MPT), as revealed by calcein fluorescence studies and the protective effect of
      cyclosporin A (CsA) on the decrease in Delta Psi(m). Levels of reactive oxygen
      species (ROS) were measured with the fluorescent probes 5-(and-6)-carboxy-2',7'
      dichlorofluorescein diacetate (DCFDA) and dihydrorhodamine 123 (DHR123).
      Treatment of the hepatocytes with clofibrate caused a significant increase in
      intracellular and mitochondrial ROS. Antioxidants such as vitamin C,
      deferoxamine, and catalase were able to protect the cells against the clofibrate
      induced loss of viability, as was CsA, but to a lesser extent. These results
      suggest that one action of clofibrate might be to impair mitochondrial function,
      so stimulating formation of ROS, which eventually contribute to cell death.

PMID- 11522452
TI  - Effect of glutathione depletion on caspase-3 independent apoptosis pathway
      induced by curcumin in Jurkat cells.
AB  - Curcumin, a yellow pigment from Curcuma longa, exhibits anti-inflammatory,
      antitumor, and antioxidative properties. Although its precise mode of action has
      not been elucidated so far, numerous studies have shown that curcumin may induce
      apoptosis in normal and cancer cells. Previously, we showed that in Jurkat cells
      curcumin induced nontypical apoptosis-like pathway, which was independent of
      mitochondria and caspase-3. Now we show that the inhibition of caspase-3 by
      curcumin, which is accompanied by attenuation of internucleosomal DNA
      fragmentation, may be due to elevation of glutathione, which increased in
      curcumin-treated cells to 130% of control. We have demonstrated that glutathione
      depletion does not itself induce apoptosis in Jurkat cells; though, it can
      release cytochrome c from mitochondria and caspase-3 from inhibition by curcumin,
      as shown by Western blot. The level of Bcl-2 protein was not affected by
      glutathione depletion even upon curcumin treatment. Altogether, our results show
      that in Jurkat cells curcumin prevents glutathione decrease, thus protecting
      cells against caspase-3 activation and oligonucleosomal DNA fragmentation. On the
      other hand, it induces nonclassical apoptosis via a still-unrecognized mechanism,
      which leads to chromatin degradation and high-molecular-weight DNA fragmentation.

PMID- 11522453
TI  - ADP stimulates the respiratory burst without activation of ERK and AKT in rat
      alveolar macrophages.
AB  - Alveolar macrophages (AM) are the first line of defense against infection in the
      lungs. We previously showed that the production of superoxide and hydrogen
      peroxide, i.e., the respiratory burst, is stimulated by adenine nucleotides (ADP
      >> ATP) in rat AM through signaling pathways involving calcium and protein kinase
      C. Here, we further show that ADP induces a rapid increase in the tyrosine
      phosphorylation of several proteins that was reduced by the tyrosine kinase
      inhibitor genistein, which also inhibited the respiratory burst. Interestingly,
      ADP did not trigger the activation of the mitogen-activated protein kinases ERK1
      and ERK2, or that of protein kinase B/AKT, a downstream target of the
      phosphatidylinositol 3-kinase (PI3K) pathway. This is in contrast to another
      stimulus of the respiratory burst, zymosan-activated serum (ZAS), which activates
      both the ERK and PI3K pathways. Thus, this study demonstrates that the receptor
      for ADP in rat AM is not coupled to the ERK and AKT pathways and, that neither
      the ERK pathway nor AKT is essential to induce the activation of the NAPDH
      oxidase by ADP in rat AM while tyrosine kinases appeared to be required. The rate
      and amount of hydrogen peroxide released by the ADP-stimulated respiratory burst
      was similar to that produced by ZAS stimulation. The absence of ERK activation
      after ADP stimulation therefore suggests that hydrogen peroxide is not sufficient
      to activate the ERK pathway in rat AM. Nonetheless, as hydrogen peroxide was
      necessary for ERK activation by ZAS, this indicates that, in contrast to ADP, ZAS
      stimulates a pathway that is targeted by hydrogen peroxide and leads to ERK
      activation.

PMID- 11522454
TI  - Formation of nanomolar concentrations of S-nitroso-albumin in human plasma by
      nitric oxide.
AB  - S-Nitrosothiols are potentially important mediators of biological processes
      including vascular function, apoptosis, and thrombosis. Recent studies indicate
      that the concentrations of S-nitrosothiols in the plasma from healthy individuals
      are lower than previously reported and in the range of 30-120 nM. The mechanisms
      of formation and metabolism of these low nM concentrations, capable of exerting
      biological effects, remain unknown. An important issue that remains unresolved is
      the significance of the reactions of low fluxes of nitric oxide (NO) with oxygen
      to form S-nitrosothiols in a complex biological medium such as plasma, and the
      impact of red blood cells on the formation of S-nitrosothiols in blood. These
      issues were addressed by exposing plasma to varying fluxes of NO and measuring
      the net formation of S-nitrosothiols. In the presence of oxygen and physiological
      fluxes of NO, the predominant S-nitrosothiol formed is S-nitroso-albumin at
      concentrations in the high nM range (approximately 400-1000 nM). Although the
      formation of S-nitrosothiols by NO was attenuated in whole blood, presumably by
      erythrocytic hemoglobin, significant amounts of S-nitrosothiols within the
      physiological range of S-nitrosothiol concentrations (approximately 80 nM) were
      still formed at physiological fluxes of NO. Little is known about the stability
      of S-nitroso-albumin in plasma, and this is central to our understanding of the
      biological effectiveness of S-nitrosothiols. Low molecular weight thiols
      decreased the half-life of S-nitroso-albumin in plasma, and the stability of S
      nitroso-albumin is enhanced by the alkylation of free thiols. Our data suggests
      that physiologically relevant concentrations of S-nitrosothiols can be formed in
      blood through the reaction of NO with oxygen and proteins, despite the low rates
      of reaction of oxygen with NO and the presence of erythrocytes.

PMID- 11522455
TI  - Does the redox status of cytochrome C act as a fail-safe mechanism in the
      regulation of programmed cell death?
AB  - It has now become recognized that one of the key events in the induction of
      apoptosis, or programmed cell death, in both plants and animals is the release of
      cytochrome c from mitochondria. It is also known that oxidative stress imposed on
      cells can have a profound effect on the onset or progression of apoptosis. Here,
      we discuss how the redox status of cytochrome c, and thus its structure, can be
      altered by the presence of reactive oxygen species (ROS) and reduced glutathione
      (GSH). We suggest that cytochrome c will only induce programmed cell death if
      present in the cytoplasm in the oxidized state, and that the presence of high
      levels of cytoplasmic GSH maintain cytochrome c in an inactive (reduced) state,
      thus behaving as a fail-safe mechanism if cytochrome c is released by
      mitochondria when programmed cell death is not the required outcome. If the redox
      status of the cell is disturbed however, perhaps in the presence of hydrogen
      peroxide, GSH concentrations will drop, the cellular E(h) will rise, and
      cytochrome c will tend towards the oxidized state, allowing programmed cell death
      to proceed. Therefore, we propose that the redox state of cytoplasmic cytochrome
      c may be a key regulator of programmed cell death.

PMID- 11522457
TI  - Heme oxygenase: a font of multiple messengers.

PMID- 11522458
TI  - Seymour S. Kety and the genetics of schizophrenia.

PMID- 11522459
TI  - Alterations of thalamic activity in schizophrenia and in response to
      antipsychotic drugs: studies in the legacy of Seymour S. Kety.

PMID- 11522460
TI  - Smoking history and nicotine effects on cognitive performance.
AB  - This study examined the effects of abstinence from smoking, of smoking history,
      and of nicotine administration on visual attention (2-Letter Search Task), verbal
      information processing (Logical Reasoning Task), and working memory (N-Back
      Tasks). Fourteen smokers, 15 ex-smokers, and 9 never-smokers took part. All
      subjects participated in a training session (when smokers had been smoking ad
      libitum) and in two subsequent test sessions after administration of 4 mg
      nicotine gum or placebo, respectively. Smokers were 12-h abstinent when they
      received gum. An effect of acute nicotine administration (independent of smoking
      history) was seen only with respect to reaction time on the 2-Letter Search Task.
      Working memory performance was related to smoking history (smokers performed most
      poorly and never-smokers best). The Logical Reasoning Task showed no effects of
      either acute or chronic nicotine exposure. The findings indicate that nicotine
      may influence focusing of attention in smokers as well as nonsmokers, and that
      trait-like differences in some cognitive domains, such as working memory, may be
      either long-term effects or etiological factors related to smoking.

PMID- 11522461
TI  - Repeated lofexidine treatment attenuates stress-induced, but not drug cues
      induced reinstatement of a heroin-cocaine mixture (speedball) seeking in rats.
AB  - Alpha-2 adrenoceptor agonists (lofexidine, clonidine) are used to alleviate short
      term opioid withdrawal in humans. In rats, acute injections of these agents
      attenuate stress-induced reinstatement of heroin and cocaine seeking at time
      points that are beyond the acute drug withdrawal phase. Here, we studied whether
      exposure to lofexidine would attenuate reinstatement of a heroin-cocaine mixture
      (speedball) seeking induced by exposure to stress or to drug-associated cues.
      Rats were trained to lever press for speedball for 10 days, and the drug
      reinforced behavior was then extinguished for 11 days in the presence (Experiment
      1) or the absence (Experiment 2) of the drug cues. Subsequently, rats were tested
      for reinstatement of drug seeking after exposure to intermittent footshock stress
      (5-15 min; Experiment 1) or the drug cues (Experiment 2). Starting on day 7 of
      training, rats received daily injections of saline or lofexidine (0.1 or 0.2
      mg/kg). Repeated lofexidine treatment significantly attenuated footshock-induced
      reinstatement, but did not alter drug cues-induced reinstatement of speedball
      seeking. In addition, lofexidine did not have a consistent effect on speedball
      self-administration and extinction behavior. Results extend previous reports with
      acute drug injections, indicating that lofexidine maintains its effect on stress
      induced reinstatement after repeated treatment. The present data also suggest
      that the neurochemical events underlying stress- and drug cues-induced relapse
      are not identical.

PMID- 11522462
TI  - Predicting relapse to alcohol and drug abuse via quantitative
      electroencephalography.
AB  - A sensitive and specific screening test that would identify the subset of
      substance-abusing patients at highest risk for relapse would constitute an
      important advance for treatment planning. This study examined the relative value
      of quantitative electroencephalography as a rapid, inexpensive, and noninvasive
      measure of relapse potential. The subjects were 107 substance-dependent patients
      enrolled in residential treatment programs. All were unmedicated and free of the
      complicating effects of major medical and neurological disorders. Structured
      clinical interview data and a 5-minute recording of the resting, eyes-closed
      electroencephalogram were obtained after patients had verifiably maintained
      abstinence for 1-5 months. Patients were then monitored for relapse or successful
      abstinence by research staff for an ensuing 6-month period. ANCOVAs of EEG power
      spectral density within pre-defined frequency bands revealed an enhanced amount
      of high frequency (19.5-39.8 Hz) beta activity among the 48 patients who later
      relapsed compared to both 59 patients who maintained abstinence and 22 additional
      subjects with no history of substance dependence. Importantly, in subsequent
      logistic regression analyses, fast beta power was found to be superior to
      severity of illness, depression level, and childhood conduct problems in
      predicting relapse. With fast beta power as the sole predictor, the sensitivity,
      specificity, and positive and negative predictive value parameters for
      discriminating outcomes were 0.61, 0.85, 0.75, and 0.74, respectively. Additional
      ANCOVAs revealed that the EEG difference between relapse-prone and abstinence
      prone groups was related to the interaction of two premorbid factors, viz.,
      childhood Conduct Disorder and paternal alcoholism. The enhancement of fast beta
      electroencephalographic activity in patients who will later relapse most likely
      originates from a premorbid and subtle dysfunction involving frontal brain
      regions.

PMID- 11522463
TI  - Dissociable effects of antagonism of NMDA and AMPA/KA receptors in the nucleus
      accumbens core and shell on cocaine-seeking behavior.
AB  - The purpose of the present experiment was to investigate the involvement of NMDA
      and AMPA/KA receptors in the nucleus accumbens core and shell in the control over
      cocaine-seeking behavior by drug-associated cues. Rats were trained under a
      second-order schedule of reinforcement for cocaine with five infusions of cocaine
      being available in each daily session. The NMDA receptor antagonist AP-5 and the
      AMPA/KA receptor antagonist LY293558 were infused directly into the core or
      shell. LY293558 infused into the core produced a dose-dependent decrease in
      responding during both the first, cocaine-unaffected interval and also after
      cocaine had been self-administered in subsequent intervals. By contrast, AP-5
      infused into the core had no effect on responding. Infusion of AP-5 into the
      shell had the limited effect of decreasing responding during the second interval
      only. There were no effects of LY293558 infused into the shell. These results
      indicate that NMDA and AMPA receptor-mediated glutamate transmission in the core
      and shell are dissociably involved in cocaine-seeking behavior controlled in part
      by drug-associated cues.

PMID- 11522464
TI  - Enduring resistance to extinction of cocaine-seeking behavior induced by drug
      related cues.
AB  - The conditioning of cocaine's pharmacological actions with environmental stimuli
      is thought to be a critical factor in long-lasting relapse risk associated with
      cocaine addiction. To study the significance of environmental stimuli in enduring
      vulnerability to relapse, the resistance to extinction of drug-seeking behavior
      elicited by a cocaine-related stimulus was examined. Male Wistar rats were
      trained to associate discriminative stimuli (S(D)) with the availability of
      intravenous cocaine (S(+)) vs. the availability of non-rewarding (S(-)) saline
      solution, and then placed on extinction conditions during which intravenous
      solutions and S(D) were withheld. The rats were then presented with the S(+) or
      S(-) alone in 60-min reinstatement sessions conducted at 3-day intervals. To
      examine the long-term persistence of the motivating effects of the cocaine S(+),
      a subgroup of rats was re-tested following an additional three months of
      abstinence during which time the rats remained confined to their home cages. Re
      exposure to the cocaine S(+) selectively elicited robust responding at the
      previously active lever. The efficacy and selectivity of this stimulus to elicit
      responding remained unaltered throughout a 34-day phase of repeated testing as
      well as following the additional extended abstinence period. In pharmacological
      tests, conducted in a separate group of rats, the dopamine (DA) D(1) antagonist
      SCH 39166 (10 microg/kg), the D(2/3) antagonist nafadotride (1 mg/kg), and the
      D(2/3) agonist PD 128907 (0.3 mg/kg) suppressed the cue-induced response
      reinstatement while the D(1) agonist SKF 81297 (1.0 mg/kg) produced a variable
      behavioral profile attenuating cue-induced responding in some rats while
      exacerbating this behavior in others. The results suggest that the motivating
      effects of cocaine-related stimuli are highly resistant to extinction. The
      undiminished efficacy of the cocaine S(+) to induce drug-seeking behavior both
      with repeated testing and following long-term abstinence parallels the long
      lasting nature of conditioned cue reactivity and cue-induced cocaine craving in
      humans, and confirms a significant role of learning factors in long-lasting
      vulnerability to relapse associated with cocaine addiction. Finally, the results
      support a role of DA neurotransmission in cue-induced cocaine-seeking behavior.

PMID- 11522465
TI  - Subtypes of mania determined by grade of membership analysis.
AB  - Classical descriptions of mania subtypes extend back to Kraepelin; however, in
      marked contrast to the study of depression subtypes, validation of mania subtypes
      by multivariate statistical methods has seldom been attempted. We applied Grade
      of Membership (GOM) analysis to the rated clinical features of 327 inpatients
      with DSM-III-R mania diagnoses. GOM is a type of latent structure multivariate
      analysis, which differs from others of this type in making no a priori
      distributional assumptions about groupings. We obtained 5 GOM Pure Types with
      good face validity. The major Kraepelinian forms of "hypomania," "acute mania,"
      "delusional mania," and "depressive or anxious mania" were validated. The major
      new finding is of two mixed mania presentations, each with marked lability of
      mood. The first of these displayed a dominant mood of severe depression with
      labile periods of pressured, irritable hostility and paranoia, and the complete
      absence of euphoria or humor. The second mixed mania Pure Type displayed a true,
      incongruous mixture of affects: periods of classical manic symptoms with
      euphoria, elation, humor, grandiosity, psychosis, and psychomotor activation,
      switching frequently to moderately depressed mood with pressured anxiety and
      irritability. This multivariate analysis validated classical clinical
      descriptions of the major subtypes of mania. Two distinct forms of mixed manic
      episodes were identified. DSM-III-R criteria did not reliably identify either of
      these two natural groups of mixed bipolar patients. As occurs in depression, this
      clinical heterogeneity of mania may influence response to drug treatments.

PMID- 11522466
TI  - Influence of different antidepressant drugs on the effect of chronic variable
      stress on restraint-induced dopamine release in frontal cortex.
AB  - The aim of this study was to evaluate the influence of an early chronic variable
      stress procedure (CVS) associated or not with repeated administration of various
      antidepressants on cortical restraint-induced dopamine (DA) release in vivo.
      Animals were subjected to the CVS schedule and one day after submitted to
      persistent administration with vehicle, desipramine (DMI, 10 mg/kg, i.p.),
      fluoxetine (FLU, 10 mg/kg, i.p.) or phenelzine (PHE; 10 mg/kg, i.p.) and later on
      exposed to a 60-min restraint period. In addition, we also explored the effect of
      acute administration of these antidepressants on cortical DA overflow in response
      to restraint in CVS treated rats. A higher increase in cortical DA release in
      response to restraint was observed in CVS animals as compared with those without
      previous CVS. Persistent, but not acute, administration with DMI, FLU and PHE
      blocked the sensitized output induced by restraint following CVS exposure.

PMID- 11522467
TI  - Prolactin response to dl-fenfluramine challenge before and after treatment with
      paroxetine.
AB  - The prolactin response to dl-fenfluramine (an indirect central serotonin agonist)
      challenge has been used to assess serotonergic function and appears to be blunted
      in depressed patients. We used this method to determine whether the serotonergic
      deficit in depressed patients is corrected by treatment with paroxetine. Prior to
      treatment with paroxetine sixteen depressed patients received a placebo challenge
      followed by a dl-fenfluramine challenge the next day. The same two challenges
      were repeated after treatment. Prolactin baseline levels were measured before
      pill administration, and then hourly for 5 hours. Fenfluramine/norfenfluramine
      levels were assayed at each time point after drug administration. Treatment with
      paroxetine significantly increased the baseline prolactin level independently of
      treatment response but positively correlated with paroxetine dose. We found that
      pre-treatment prolactin response to dl-fenfluramine challenge did not predict
      clinical response to paroxetine, nor did the prolactin response change
      significantly after treatment. There was no significant difference in the post
      treatment prolactin response between treatment responders and treatment non
      responders. We found evidence of increased prolactin levels that may reflect
      effects of paroxetine in enhancing serotonin levels. Acute release of serotonin
      as measured by the prolactin response to fenfluramine is not altered by
      paroxetine treatment.

PMID- 11522468
TI  - Guanfacine treatment of cognitive impairment in schizophrenia.
AB  - Norepinephrine plays a significant role in the working memory functions of the
      prefrontal cortex by its actions at alpha-2a noradrenergic receptors. Guanfacine
      has demonstrated efficacy in reversing working memory deficits in non-human
      primate. In the present study the effect of guanfacine adjunctive treatment to
      neuroleptics on the cognitive performance of schizophrenic patients was
      investigated in a four week, placebo-controlled, double-blind, parallel design
      trial. The primary analyses revealed no significant differences between
      guanfacine and placebo treatment; however, exploratory non-parametric statistics
      revealed some significant and some trend differences between guanfacine and
      placebo on spatial working memory test performance and CPT reaction time in those
      subjects treated with atypical neuroleptics.

PMID- 11522469
TI  - Inverse agonist properties of antipsychotic agents at cloned, human (h) serotonin
      (5-HT)(1B) and h5-HT(1D) receptors.
AB  - The actions of diverse antipsychotics at cloned h5-HT(1B) and h5-HT(1D) receptors
      were examined employing [3H]-GR125,743 and [35S]-GTPgammaS for determination of
      affinities and efficacies, respectively. Compared with hD(2) receptors,
      haloperidol, chlorpromazine and olanzapine showed markedly (>100-fold) lower
      affinity for h5-HT(1D) and h5-HT(1B) receptors at which they expressed inverse
      agonist properties. Clozapine, risperidone and ocaperidone likewise behaved as
      inverse agonists at h5-HT(1B) and h5-HT(1D) receptors but their affinities were
      only approximately 10-fold lower than at hD(2) receptors. Moreover, ziprasidone,
      S16924 and ORG5222 interacted at h5-HT(1B) and h5-HT(1D) receptors with
      affinities similar to hD(2) sites. While S16924 and ORG5222 were inverse agonists
      at h5-HT(1B) and h5-HT(1D) sites, ziprasidone was an inverse agonist at h5-HT(1D)
      receptors yet a partial agonist at h5-HT(1B) receptors. These actions of
      antipsychotics were abolished by the selective, neutral antagonist, S18127. In
      conclusion, with the exception of ziprasidone, all antipsychotics were inverse
      agonists at h5-HT(1B) and h5-HT(1D) receptors, although they differed markedly in
      their potency at these sites as compared to hD(2) receptors.

PMID- 11522470
TI  - Caesarean section birth produces long term changes in dopamine D1 receptors and
      in stress-induced regulation of D3 and D4 receptors in the rat brain.
AB  - Schizophrenia is associated with increased birth complications and altered
      mesocorticolimbic dopaminergic (DA) transmission, whereas stress also influences
      psychotic symptoms. Given this, the present study tested effects of two birth
      complications, Caesarean section (C-section) birth with or without acute global
      anoxia, on brain DA receptors in rats at adulthood. Effects of repeated stress at
      adulthood were also tested. Before stress, C-sectioned rats showed increased D1
      like receptor binding in limbic areas, compared to vaginally born controls. There
      were no differences between birth groups in D2-like, D3, or D4-like receptor
      binding before stress. After stress, C-sectioned animals showed decreased D3
      receptors in accumbens and increased D4-like receptors in dorsal striatum,
      accumbens, and olfactory tubercles, compared to vaginal birth. This occurred
      because stress upregulated D3 receptors only with vaginal birth and upregulated
      D4-like receptors only with C-section. Animals born by C-section + anoxia showed
      no change in DA receptors relative to vaginal birth, before or after stress. It
      is concluded that interactions between an individual's experience of stress at
      adulthood, together with other environmental events in their history, such as
      birth complications, can be important determinants of brain DA receptor levels.

PMID- 11522471
TI  - Serotonin-dopamine interactions in the control of conditioned reinforcement and
      motor behavior.
AB  - These studies addressed the question of serotonin (5-HT)-dopamine (DA)
      interactions with regard to reward-related behavior and motor activity in rats.
      The first experiment evaluated the effect of chronic treatment with fluoxetine (7
      mg/kg/day), a serotonin-selective reuptake inhibitor, and buproprion (15
      mg/kg/day), a dopamine reuptake inhibitor, on responding for conditioned
      reinforcement (CR). Chronic fluoxetine, but not buproprion, enhanced CR
      responding, and also potentiated cocaine-induced increases in CR responding. In
      the second experiment, animals received intra-accumbens infusions of either 5-HT
      (0, 1, 5, and 10 microg) or DA (10, 20 microg) prior to the conditioned
      reinforcement test. Dopamine, but not 5-HT, selectively facilitated CR
      responding, although 5-HT non-specifically increased responding as well. In the
      third and fourth experiments, it was demonstrated that intra-accumbens 5-HT
      causes increased motor activity, which was partially blocked by DA antagonists.
      The results suggest that chronically increased levels of 5-HT may facilitate
      reward-related behavior, but most likely via indirect modulatory mechanisms
      affecting general arousal and motor tone.

PMID- 11522474
TI  - Passive skin penetration enhancement and its quantification in vitro.
AB  - The poor penetration of drugs into the skin (and, partially, the permeation
      across the stratum corneum) often limits the efficacy of topical formulations.
      Basically, skin penetration can be enhanced by the following strategies: (i)
      increasing drug diffusivity in the skin; (ii) increasing drug solubility in the
      skin, and/or (iii) increasing the degree of saturation of the drug in the
      formulation. In this article, we review the literature with respect to: (i)
      chemical penetration enhancers, which have been shown to influence the
      diffusivity and/or solubility of the drug in the skin and (ii) supersaturated
      formulations, in which the degree of saturation of the drug is increased compared
      to conventional formulations. In addition, three different in vitro methods,
      specifically, classic diffusion cell studies, attenuated total-reflectance
      Fourier transform infrared spectroscopy, and tape stripping in conjunction with
      an appropriate analytical technique, are considered, emphasizing their
      application to obtain quantitative values for skin transport parameters and to
      separate the kinetic or thermodynamic effects of an enhancement strategy.

PMID- 11522475
TI  - Combined effect of oleic acid and propylene glycol on the percutaneous
      penetration of tenoxicam and its retention in the skin.
AB  - The influence of oleic acid (OA) on the in vitro percutaneous absorption of
      tenoxicam (TEN) and its combined effect with propylene glycol (PG) was studied
      using Franz-type diffusion cells. Furthermore, at defined concentrations of OA,
      complexes of the drug with cyclodextrins (MbetaCD and gammaCD) were added because
      their combined use may be an interesting approach to raise TEN flux. In addition,
      the amount of TEN retained in the skin after topical administration of several
      formulations was determined. It was found that OA content markedly increased TEN
      absorption when compared to the control gel; the highest drug flux was obtained
      by 15% of OA. The absorption rate of TEN increased in parallel with increasing OA
      concentration, due to the alteration of the stratum corneum caused by this
      enhancer. Moreover, the action of OA is likely to be strongly dependent on the
      vehicle used since drug penetration tended to increase with increasing PG content
      in the vehicle, especially at the high OA concentrations. Contrary to our
      expectations, addition of CD complexes did not produce a significant further
      enhancement. Skin pretreatment with OA, independently of the vehicle used to
      dissolve the fatty acid, dramatically improved TEN percutaneous penetration. The
      amount of TEN retained in the skin was related to the flux values obtained with
      each formulation.

PMID- 11522476
TI  - In vitro assessment of the mucoadhesion of cholestyramine to porcine and human
      gastric mucosa.
AB  - Previous in vivo studies have suggested that the extended gastric residence and
      uniform intragastric distribution of cholestyramine may be due to mucoadherent
      properties. This series of in vitro investigations explored the possibility of
      the anion exchange resin exhibiting bioadhesive behaviour, and investigated the
      characteristics, such as particle size and surface charge, that may affect it.
      Tensile strength measurements were carried out to determine the mucoadhesion of
      cholestyramine and other test materials (resin particulates, polymers and
      hydrogels) with varying adhesive properties, to isolated porcine and human
      gastric mucosa. Optimal instrumental parameters for the system were determined
      initially and used; all procedures were carried out at room temperature (22
      degrees C). The particle size of cholestyramine did not affect mucoadhesion to
      either porcine or human gastric mucosa (P=0.673, porcine; P=0.969, human), whilst
      anionic exchangers were found to provide better mucoadhesion than cationic
      exchangers (P=0.0002, porcine; P=0.0009, human). In some instances, it was found
      that the detachment forces recorded were lower with human gastric mucosa than
      with porcine gastric mucosa, although this was not consistently statistically
      significant. A rank order of mucoadhesion was constructed from a comparison of
      cholestyramine with eight other test materials. Cholestyramine produced the
      second highest degree of mucoadhesion, with Carbopol producing the greatest
      adhesion. Dextran and polyethylene glycol did not display good mucoadhesion under
      these conditions. From the findings presented here, we have found that
      cholestyramine demonstrates good mucoadhesion to both porcine and human gastric
      mucosa when compared to other known bioadhesives. It is suggested that particle
      size does not contribute to this mucoadherent behaviour but the surface charge of
      the resin has a significant part to play.

PMID- 11522477
TI  - Effects of microemulsions on the stratum corneum and hydrocortisone penetration.
AB  - We tested a high-water-content hydrophilic microemulsion (ME 1) and a low-water
      content lipophilic microemulsion (ME 2) for their suitability for use in
      dermatology, in general, and as alternative hydrocortisone (HC) vehicles, in
      particular. The lipophilic component of both study products was isopropyl
      myristate. The surfactant/cosurfactant system of ME 1 consisted of two sucrose
      esters and that of ME 2 was a mixture of Tagat S and Plurololeat. Both MEs showed
      no in vitro irritability in the hen's egg test on chorioallantoic membranes. In
      14 subjects, stratum corneum water content was determined by corneometry and
      transepidermal water loss (TEWL) by the Tewameter before and after 3 days use of
      ME 1 or ME 2 as well as on two untreated control sites. ME 1 produced dehydration
      and increased TEWL as evidence of barrier compromise. ME 2 also produced an
      increase in TEWL but had no dehydrating effect. Subjects then underwent
      standardized washing with a surfactant solution. Under these conditions,
      pretreatment with ME 2 also produced dehydration, but to a lesser extent than did
      pretreatment with ME 1. In the same subjects, the impact of the two MEs on HC
      penetration (0.5%, 24h occlusion) was evaluated in terms of the chromameter
      determined blanching effect compared with that on a site treated only with an
      occlusive film dressing. The comparator was an ambiphilic cream (Basiscreme (BC)
      Deutscher Arzneimittel Codex (German Formulary)). Irritative skin redness
      produced by ME 1 was significant and that produced by ME 2 was slight but
      visible, compared with BC. HC penetration was demonstrable from all the study
      products via the blanching effect and was significantly greater from ME 1 and
      slightly greater from ME 2 than from BC. However, neither ME would improve HC
      therapy because the irritative effects were so great that the blanching effect of
      HC formulated in ME 1 was significantly smaller and that of HC in ME 2 slightly
      smaller than that of HC formulated in BC.

PMID- 11522478
TI  - Influence of the spacer on the inhibitory effect of different polycarbophil
      protease inhibitor conjugates.
AB  - Within the present study various polycarbophil (PCP)-serine protease inhibitor
      conjugates were synthesized and the influence of different spacers on their
      inhibitory efficacy was evaluated in vitro. Results demonstrated that 4.2+/-0.15
      units (n=3; +/-SD) of alpha-chymotrypsin were inhibited by 50% utilizing 0.86%
      (w/v) of a PCP-tetramethylenediamine (TMDA)-chymostatin 20:1 conjugate. In
      contrast, only 0.6+/-0.05 units (n=3; +/-SD) of alpha-chymotrypsin were inhibited
      by a corresponding PCP-poly(ethylene glycol) (PEG)-chymostatin conjugate.
      Inhibitory effects of PCP-TMDA-antipain and -elastatinal conjugates towards
      trypsin and elastase, respectively, were also significantly higher (P<0.05) than
      those of corresponding PCP-PEG-inhibitor conjugates. Hence, the great impact of
      the molecular size as well as the structure of the spacer on resulting polymer
      inhibitor conjugates could be demonstrated. The small and rigid C4-spacer TMDA
      (molecular weight (MW) 161.1) was thereby shown to be highly advantageous over a
      long, hydrophilic and flexible PEG-diamine spacer (MW 3400). Results obtained
      should provide helpful basic knowledge for the development of mucoadhesive
      polymer-inhibitor conjugates used as auxiliary agents for the oral administration
      of peptide drugs.

PMID- 11522479
TI  - Enhancing the permeation of marker compounds and enaminone anticonvulsants across
      Caco-2 monolayers by modulating tight junctions using zonula occludens toxin.
AB  - Zonula occludens toxin (Zot), a protein elaborated from Vibrio cholerae, has been
      shown to be capable of reversibly opening tight junctions between intestinal
      cells The objective of this study was to examine the effect of Zot on the flux of
      various molecules across Caco-2 cell monolayers. In addition, the transport of a
      series of anticonvulsants, the enaminones was also evaluated in the presence of
      Zot. The flux of [(14)C]mannitol, [(14)C]inulin and various enaminones across
      Caco-2 cell monolayers (n=6) was examined after pre-incubation for 1h with Zot (0
      or 4000ng/ml) or phosphate-buffered saline (PBS). At the end of the incubation
      period, the flux of radiolabeled compounds or enaminones (1x10(-4)M) was assessed
      over a 2-h period. In addition, dose-response studies with Zot (0, 1000, 2000 or
      4000ng/ml) were performed using mannitol. The flux of both mannitol and inulin
      significantly increased (P<0.05) in the presence of Zot. The transport of the
      enaminones with Zot ranged from 9.42 to 26.83x10(-5)cm/s vs. 4.68 to 13.83x10(
      5)cm/s without Zot. Zot significantly increased the transport of all agents
      tested. This suggests that the co-administration of drugs with Zot may be a
      useful delivery strategy to increase the intestinal permeability and hence oral
      absorption of poorly bioavailable agents.

PMID- 11522480
TI  - In vivo-in vitro study of biodegradable and osteointegrable gentamicin bone
      implants.
AB  - Three implants composed of phosphate (25% hydroxyapatite, 75% tricalcium
      phosphate), 20% poly(DL-lactide) (DL-PLA; weight-average molecular weight (Mw),
      30 kD) and 3% gentamicin sulphate (GS) were assayed in vitro and in vivo to study
      their release profiles as potential drug delivery systems to prevent or treat
      osteomyelitis. To prolong GS release, some implants were coated with poly(lactide
      co-glycolide) (PLGA; Mw, 100 kD; I-PLGA) or DL-PLA (Mw, 200 kD; I-PLA). GS levels
      were measured in bone, kidney and blood after implantation into the femur of
      rats. The release profiles show a burst in the first few days, followed by a
      slower release rate. After I-PLA implantation, bone antibiotic concentrations
      higher than the minimum bactericidal concentration were maintained for 4 weeks. A
      linear correlation between in vitro and in vivo GS release was found to continue
      until complete drug release. Histological and radiological analysis showed that
      the implants were well tolerated and gradual new bone formation was observed.

PMID- 11522481
TI  - Bioavailability of diazepam from aqueous-organic solution, submicron emulsion and
      solid lipid nanoparticles after rectal administration in rabbits.
AB  - The bioavailability of diazepam in rabbits after rectal administration of three
      formulations: organic-aqueous Relsed rectal solution (containing ethanol, benzyl
      alcohol and propylene glycol), submicron emulsion and solid lipid nanoparticles
      (SLN), was studied. Submicron emulsion contained MCT oil (20% w/w), egg lecithin
      and poloxamer; SLN were prepared with cetyl palmitate 10% w/v and non-ionic
      emulsifying agent, Plantacare. All formulations contained 4 mg/ml of diazepam and
      the dose administrated to rabbits was 2 mg/kg. In both submicron preparations
      nearly the same mean size of the dispersed particles (201-206 nm) and the
      fraction of the free drug in aqueous phase (0.9-1.5%) was determined. Besides
      very moderate prolongation of drug release, the submicron emulsion as a vehicle
      did not alter pharmacokinetics of diazepam when compared with the solution: the
      mean C(max) was 48.9+/-24.0 and 49.5+/-17.0 ng/ml, and area under the curve was
      134.0+/-42.3 and 186.8+/-59.8 ng h/ml, for solution and emulsion, respectively.
      The low relative bioavailability, 47% compared to the solution, was observed
      after administration of SLN. Transmission electron microscopy pictures revealed
      that some of diazepam is present on the surface of the SLN and this fraction was
      immediately absorbed, while the diffusion of the drug in the solid core was not
      efficient enough to allow a complete release. It may be concluded that submicron
      emulsion may be a good choice of an ethanol-free drug formulation, but lipid
      matrix, which is solid at body temperature, is not advantageous system for
      diazepam rectal delivery, even if delivered as a submicron dispersion.

PMID- 11522482
TI  - Effects of erythrocytes and serum proteins on lung accumulation of lipoplexes
      containing cholesterol or DOPE as a helper lipid in the single-pass rat lung
      perfusion system.
AB  - Plasmid DNA-cationic liposome complexes (lipoplexes) accumulate in the lung to a
      great extent immediately after intravenous administration, and gene expression
      occurs predominantly in the lung. However, the detailed mechanisms underlying the
      lung accumulation of lipoplexes are not fully understood. In this study, we
      investigated the effect of blood components on the lung accumulation of
      lipoplexes using a single-pass rat lung perfusion system. Two types of
      lipoplexes, Chol-containing lipoplex ([(32)P]DNA-DOTMA/Chol liposome complex) and
      DOPE-containing lipoplex ([(32)P]DNA-DOTMA/DOPE liposome complex), pre-incubated
      with whole blood, serum, or erythrocytes, were injected into the perfused lung
      via an artery. Similarly to in vivo observations, extensive lung accumulation was
      observed for both types of lipoplexes after incubation with whole blood during a
      single passage. The (32)P-labeled lipoplexes pre-incubated with erythrocytes
      showed similar lung accumulation, whereas their lung accumulation after
      incubation with serum was significantly reduced, suggesting that erythrocytes
      would be more responsible blood components for extensive uptake by the perfused
      lung. However, there was a clear difference in the amounts of the accumulated
      erythrocytes after intra-arterial injection between the two lipoplex
      formulations. A significant degree of erythrocyte accumulation was observed when
      the DOPE-containing lipoplex was injected, whereas the Chol-containing lipoplex
      failed to induce any significant erythrocyte accumulation in the lung. In vitro
      experiments showed that the major fraction of both lipoplexes was bound to
      erythrocytes. These data suggested that Chol-containing lipoplexes bound to
      erythrocytes before injection dissociate from the erythrocytes and are
      transferred to the lung capillary endothelial cells during their passage through
      the lung. In contrast, DOPE-containing lipoplexes bound to erythrocytes cause
      aggregation and are embolized in the lung capillary with erythrocytes. Thus, the
      present study demonstrated that the interaction with erythrocytes plays an
      important role in the lung accumulation of lipoplexes and that neutral helper
      lipid significantly affects this interaction.

PMID- 11522483
TI  - Eudragits: role as crystallization inhibitors in drug-in-adhesive transdermal
      systems of estradiol.
AB  - A transdermal steroidal delivery system usually contains a high concentration of
      drug to obtain high drug fluxes. The present investigation involved the
      development of drug-in-adhesive transdermal systems of estradiol using
      synthesized acrylate copolymer (EA) of 2-ethylhexyl acrylate and acrylic acid.
      The effect of several variables such as varying drug polymer ratios, effect of
      Eudragit RL PO and Eudragit E PO and effect of drying temperatures on prevention
      of drug crystallization in the formulation matrix was investigated. The systems
      free from drug crystals were evaluated and compared with a marketed formulation
      with respect to its skin permeation profile. The optimized formulation was also
      subjected to accelerated stability testing. Eudragit RL PO and Eudragit E PO were
      found to be effective as crystallization inhibitors in the transdermal matrix
      systems tested. Formulations fabricated with Eudragit E PO gave transparent
      systems with good film properties and a higher skin permeation profile as
      compared to that of the marketed system. Higher temperature and humidity
      conditions facilitated the formation of drug crystals, whereas no crystals were
      observed in the formulation matrix at 23+/-0.5 degrees C and at 30+/-1 degrees C
      for the period of 6 months studied.

PMID- 11522484
TI  - Properties of lipophilic matrix tablets containing phenylpropanolamine
      hydrochloride prepared by hot-melt extrusion.
AB  - The objective of the present study was to investigate the influence of
      formulation factors on the physical properties of hot-melt extruded granules and
      compressed tablets containing wax as a thermal binder/retarding agent, and to
      compare the properties of granules and tablets with those prepared by a high
      shear melt granulation (MG) method. Powder blends containing phenylpropanolamine
      hydrochloride, Precirol and various excipients were extruded in a single-screw
      extruder at open-end discharge conditions. The extrudates were then passed
      through a 14-mesh screen to form granules. The extrusion conditions and the
      optimum amount of wax to function as the thermal binder were dependent on the
      properties of the filler excipients. At the same wax level, drug release from
      tablets decreased in the order of using microcrystalline cellulose (MCC), lactose
      and Emcompress as the filler excipient. The observed differences in the
      dissolution properties of the tablets were due to the differences in the
      solubility, swellability and density of the filler excipients. Replacing Precirol
      with Sterotex K, a higher melting point wax, resulted in slightly increased
      dissolution rates, when the extrusion was performed at the same temperature
      conditions. Hot-melt extruded granules were observed to be less spherical than
      high-shear melt granules and showed lower values of bulk/tap densities. However,
      tablets containing MCC or lactose granules prepared by hot-melt extrusion (HME)
      exhibited higher hardness values. Slower drug release rates were found for
      tablets containing MCC by HME compared with MG. Analysis of the hot-melt extruded
      granules showed better drug content uniformity among granules of different size
      ranges compared with high-shear melt granules, resulting in a more reproducible
      drug release from the corresponding tablets.

PMID- 11522485
TI  - Biodegradable polymer nanocapsules containing a sunscreen agent: preparation and
      photoprotection.
AB  - Biodegradable polymer nanocapsules containing the lipophilic sunscreen, Parsol
      MCX (OMC), as the oil core were prepared by solvent displacement. We investigated
      the influence of polysorbate 85 (P-85) and poloxamer 188 (P-188) as stabilizing
      agents, the OMC loading capacity and the photoprotective potential of the
      formulations. The formation of nanocapsules is probably due to an interfacial
      instability arising from rapid diffusion of the solvent across the interface. The
      effectiveness of the stabilizing agents was attributed to their ability to
      inhibit coalescence during solvent diffusion. P-85 was a better stabilizer of
      poly(epsilon-Caprolactone)-nanocapsules than P-188. The OMC loading capacity was
      high (99+/-1% of OMC initial concentration). The in vitro release of OMC
      nanocapsules is governed by hydrophobicity and crystallinity of the polymer and
      by the high lipophilicity of the drug. The OMC-nanocapsules provided partial
      protection against UV-induced erythema, in a manner significantly better than a
      conventional gel.

PMID- 11522486
TI  - The effect of formulation and concentration of cholesteryl butyrate solid lipid
      nanospheres (SLN) on NIH-H460 cell proliferation.
AB  - Experimental factorial design was used to evaluate the influence of two factors
      involved in producing cholesteryl butyrate (chol-but) solid lipid nanospheres
      (SLN), microemulsion formulation and microemulsion/water ratio, on the effect of
      the SLN on the proliferation of NIH-H460, a non-small-cell lung carcinoma; six
      experimental settings were tested. The cells were treated with scalar
      concentrations of cholesteryl butyrate (from 0.008 to 1.000 mM) for each
      experimental condition; NIH-H460 cell growth was inhibited in all cases. The best
      experimental setting provided complete inhibition at 0.125 mM chol-but, while at
      the same concentration sodium butyrate provided only 38% inhibition.

PMID- 11522487
TI  - Electrolyte- and pH-stabilities of aqueous solid lipid nanoparticle (SLN)
      dispersions in artificial gastrointestinal media.
AB  - The influence of artificial gastrointestinal (GI) media on the physical stability
      of solid lipid nanoparticle (SLN) formulations consisting of different lipids and
      various surfactants/stabilizers has been investigated in vitro, with respect to
      ionic strength and pH. Laser diffractometry and zeta potential measurements were
      the techniques applied. Some SLN formulations already showed aggregation/particle
      growth in the presence of electrolytes at neutral pH. Other lipid nanodispersions
      remained physically stable with respect to the influence of electrolytes, but
      were pH-sensitive. It was possible to produce SLN that were GIT (gastrointestinal
      tract) stable by an optimized stabilizer composition. There is no optimal
      surfactant mixture for stabilization of any lipid, e.g. SLN consisting of the
      lipid Cutina CP showed GIT stability in combination with the stabilizer sugar
      ester S1670, whereas the stabilization with the surfactant mixture Tween 80/Span
      85 was not effective. Vice versa, the emulsifier Pluronic F68 stabilized the
      lipid Compritol ATO 888 but not the lipid Imwitor 900 sufficiently to avoid
      aggregation of the SLN dispersion in artificial GI media. The stabilizing
      properties depend obviously on the specific interactions of the lipid matrix with
      the emulsifier, e.g. anchoring of the stabilizer on the lipid surface and density
      on the surface.

PMID- 11522488
TI  - Stress relaxation studies of granules as a function of different lubricants.
AB  - Viscoelastic properties of granules may be studied using stress relaxation. The
      effect of viscoelastic properties of different lubricants, namely magnesium
      stearate (Mgst), talc and precirol, on granule compaction properties was examined
      using texture analyzer TA-XT2i at low pressure. Normalized compact curves of
      stress relaxation have been discussed in relation to some parameters
      (flowability, porosity, viscoelasticity as well as particle size). The literature
      shows that viscoelasticity is always present and it produces an accompanying
      plastic deformation.This study revealed that bonding in compacted granules
      lubricated with Mgst was higher than those in compacts lubricated with the other
      two lubricants being studied. When studying the partial porosity of granule beds,
      we see that this is the result of stored energy, like the tablet case and the
      problem of its capping. The small stress relaxation due to talc or precirol
      suggested that these materials deformed principally by energy storage. However, a
      qualitative characterization of Mgst as tablet lubricant would be that it avoids
      the accumulation of stress in the compact that causes the problem of capping due
      to the entrapped air and therefore facilitates the optimization of pharmaceutical
      manufacturing. It has been possible to normalize stress relaxation using the
      Wischert model, represented by the sum of several exponentials, according to the
      nature of the lubricant. The use of texture analyzer TA-XT2i was considered to be
      a good technique for the evaluation of the stress relaxation of solid particles
      in the compression process at low pressure. It permitted the observation that
      viscoelasticity is influenced by the lubricant used. The brittle fracture index,
      like Carr's index values, has been correlated with the viscoelastic
      characteristics of granules.

PMID- 11522489
TI  - Determination of the disintegration behavior of magnetically marked tablets.
AB  - The disintegration behavior of different tablets that were marked as magnetic
      dipoles by the incorporation of ferromagnetic black iron oxide and subsequent
      magnetization was studied using a specially developed measurement setup. This
      novel apparatus records the magnetic induction generated by the magnetic dipole
      moment of the tablets during their disintegration. It was found that the observed
      decrease of the magnetic induction can be used for a quantitative determination
      of the disintegration of tablets. In particular, it could be shown that the
      magnetic data provide information about the disintegration mechanism. For tablets
      with a minor influence of swelling on the disintegration mechanism a linear
      decline of the magnetic fluxes was observed. After addition of swelling
      disintegrants (crospovidone) the decline of the magnetic flux could be fitted by
      an exponential function, indicating the involvement of a disintegration force.
      Furthermore, the data demonstrate that using modern multichannel biomagnetic
      measurement equipment the monitoring of the disintegration behavior of
      magnetically marked tablets in humans will be possible.

PMID- 11522490
TI  - Development and validation of a nonaqueous titration with perchloric acid to
      determine sparfloxacin in tablets.
AB  - A simple, rapid and inexpensive method for the determination of sparfloxacin in
      tablets is described. The procedure is based on the use of volumetric dosage in a
      nonaqueous medium in glacial acetic acid with 0.1 M perchloric acid. The method
      validation yielded good results and included precision and accuracy. It was also
      found that the excipients in the commercial tablet preparation did not interfere
      with the assay.

PMID- 11522491
TI  - Controlled release of tramadol hydrochloride from matrices prepared using
      glyceryl behenate.
AB  - An inert matrix to control the release of tramadol HCl was prepared using
      glyceryl behenate as a matrix-forming agent. The matrices were prepared by either
      direct compression of a physical mixture of the drug and the matrix-forming agent
      or by compression of granules prepared by hot fusion of the drug and the matrix
      forming agent. The hot fusion method was found to be more effective than
      compression of physical mixtures in retarding the release of the drug from the
      matrix. Drug release was adjusted by using release enhancers, such as
      microcrystalline cellulose and lactose, and the results showed that higher
      release rates were obtained using lactose. However, the release of the drug was
      independent of the compression force and the pH of the dissolution medium. This
      study showed that glyceryl behenate is an appropriate waxy material that can be
      used as a matrix-forming agent to control the release of a water-soluble drug
      such as tramadol HCl.

PMID- 11522492
TI  - The use of mercury porosimetry in assessing the effect of different binders on
      the pore structure and bonding properties of tablets.
AB  - This study investigated the effect of binders with different deformability
      characteristics on the pore structure of tablets composed of binary mixtures. The
      pore structure was evaluated using mercury porosimetry. The pore size
      distribution in tablets of both individual components and binary mixtures
      indicated that the pores in pure binder tablets appeared not to exist to the same
      degree in composed tablets and were therefore unlikely to substantially
      contribute to the pore structure. It is therefore suggested that, because the
      binder undergoes extensive deformation and shearing during compaction, it will
      exist as relatively small lumps or aggregates or even primary particles that are
      located between the compound particles. Most of the pores in the binary tablets
      studied were thus found between particles of the compound and the binder phase.
      The most deformable binder, polyethylene glycol 3000, had the greatest effect on
      pore structure, reflected in the greatest increase in tablet strength. An attempt
      was also made to use mercury porosimetry data to qualitatively assess the effect
      of a binder on the dominating bond types in a tablet. The results indicated that
      addition of a binder caused a decrease in the probability of forming solid
      bridges.

PMID- 11522493
TI  - Evaluation of paracetamol suppositories by a pharmacopoeial dissolution test-
      comments on methodology.
AB  - Ph.Eur. and BP have introduced a dissolution apparatus for suppositories.
      Suitability of the apparatus for quality control of paracetamol suppositories was
      evaluated and the effect of experimental conditions on dissolution profiles was
      studied. Paracetamol suppositories containing 80-500 mg of the drug, on fatty
      base, were obtained from four manufacturers (A, B, C, D). The diffusion cell was
      modified by incorporation of an in-built thermoprobe and large difference (up to
      1.7 degrees C) between temperature in the water-bath and in the dissolution
      chamber was observed. This effect was avoided by increasing the length of tubing
      immersed in the thermostat at the inlet of the cell. The most reproducible
      results were observed for A and C suppositories, however from suppository C the
      total dose of paracetamol was released after 3.5-4.5 h while the release from
      suppository A was slow with only 40-87% of the total dose liberated during 6 h.
      Suppositories B did not melt at 37 degrees C and less than 5% of the drug was
      released. Fast release was observed after melting when the temperature was
      elevated to 39.5 degrees C. The results demonstrate clearly that essentially
      complete melting of a suppository in the dissolution chamber is required for an
      appropriate dissolution of paracetamol in vitro. Disintegration time, softening
      time, drop point and particle size of the suspended drug were measured and the
      relevance of these parameters for dissolution behaviour of the preparations was
      discussed.

PMID- 11522494
TI  - A case study of preservation of semi-solid preparations using the European
      Pharmacopoeia test: comparative efficacy of antimicrobial agents in zinc gelatin.
AB  - The present study was undertaken with the aim of finding an alternative
      preservative system to methyl parahydroxybenzoate in zinc gelatin, which was
      described in the monographs of the Swiss Pharmacopoeia (until Ph. Helv. 8) and in
      previous editions of the German Pharmacopoeia (until DAB 7). This antimicrobial
      agent has now been withdrawn in the DAB, because of its potential allergy risks.
      As for the USP and DAB-DDR zinc gelatin preparations, they have always been
      devoid of any preservative agent, probably relying on the mild antimicrobial
      activity of zinc. A literature survey did not reveal if such an aqueous
      preparation containing the water-insoluble zinc oxide shows efficacious
      antimicrobial activity by itself. Thus, a comparative evaluation of differently
      preserved zinc gelatin preparations was performed using a test for the efficacy
      of antimicrobial preservation that has been modified with regard to the European
      Pharmacopoeia (EP) test to take into account the solid state of the preparations
      and the bactericidal effect of the zinc. Three zinc gelatin preparations were
      checked, either: (i), without any agent; or (ii), with 0.1% methyl
      parahydroxybenzoate; or (iii), with 0.5% phenoxyethanol, a broad-spectrum
      antimicrobial agent almost devoid of allergy risks. The three preparations behave
      quite differently, in particular with respect to fungi. All three preparations
      passed the modified EP test as far as bacteria are concerned. Even zinc gelatin
      without preservative is very effective, not only because of the mild
      antimicrobial activity of zinc (the soluble fraction of zinc oxide in the liquid
      phase of zinc gelatin was determined to be 13 microg/ml), but most probably
      because of the low water activity of the preparation (measured as around 0.81),
      as shown by the absence of growth of a zinc-resistant strain of Pseudomonas
      aeruginosa. Zinc gelatin preserved with methyl parahydroxybenzoate has a weak,
      although satisfactory, activity against Staphylococcus aureus. Regarding fungi,
      gelatin without an antimicrobial agent and that preserved with methyl
      parahydroxybenzoate meet the requirements for efficacy against Candida albicans,
      but are only bacteriostatic against Aspergillus niger. As for zinc gelatin
      preserved with phenoxyethanol, it displays the best activity against C. albicans
      and, above all, appears to be the only formulation exhibiting fungicidal activity
      against A. niger. It is therefore recommended to preserve zinc gelatin with this
      antimicrobial agent, as recently adopted in Supplement 2000 of the Swiss
      Pharmacopoeia.

PMID- 11522496
TI  - Comparison of laser-Doppler flowmetry with biochemical indicators of endothelial
      dysfunction related to early microangiopathy in Type 1 diabetic patients.
AB  - The aim of this study was to compare biochemical markers of endothelial
      activation with microcirculation measured by laser-Doppler flowmetry in Type 1
      diabetic patients with or without microangiopathy. A total of 44 Type 1 diabetic
      patients were subdivided into those with (n=24) and without (n=20)
      microangiopathy according to ophthalmological findings and the presence or
      absence of microalbuminuria. The control group consisted of 25 healthy people of
      comparable age, sex, and body mass index. Postocclusive reactive hyperemia (PORH)
      and thermal hyperemia (TH, at 44 degrees C) were measured at the forearm. Serum N
      acetyl-beta-glucosaminidase (NAG) activity, serum E-selectin, and ICAM-1
      concentrations were used as biochemical markers of endothelial dysfunction. A
      significantly lower velocity of perfusion increase during postocclusive hyperemia
      (PORH(max) x t(1)(-1)) and during thermal hyperemia (TH(max) x t(2)(-1)) (P<.01)
      were accompanied by higher serum NAG activity (20.9+/-4.6 vs. 16.3+/-2.5 U l(-1),
      P<.01) in diabetic patients with microangiopathy as compared to healthy persons.
      An inverse relationship was found between PORH(max) x t(1)(-1) and NAG (r=-.33)
      results in diabetic patients. In addition, higher mean values of serum NAG
      activity, E-selectin, and ICAM-1 concentrations were associated with
      significantly lower values of microcirculation parameters (PORH(max) x t(2)(-1)
      and TH(max) x t(2)(-1)) in six patients without microangiopathy who had at least
      one of the above biochemical markers higher than mean+2 S.D. range. We suggest
      that serum NAG activity, E-selectin, and ICAM-1 concentrations may be used
      together with laser-Doppler flowmetry in Type 1 diabetic patients as early
      indicators of vascular changes in very early stage of diabetic microangiopathy.

PMID- 11522497
TI  - Long-term effect of epalrestat, an aldose reductase inhibitor, on the development
      of incipient diabetic nephropathy in Type 2 diabetic patients.
AB  - The aim of the present study was to elucidate the long-term effect of epalrestat,
      an aldose reductase inhibitor (ARI), on renal function in patients with type 2
      diabetes mellitus showing microalbuminuria. Patients were allocated to two groups
      (cases and controls) matched for age, BMI, and the extent of urinary albumin
      excretion (UAE). Thirty-five type 2 diabetic patients presenting microalbuminuria
      were included in this study: cases were treated with epalrestat (150 mg/day) for
      5 years. No significant changes were found in blood pressure, HbA1c, and total
      cholesterol in either group during the observation period. In the control group,
      UAE increased significantly (P<.01) from 82+/-12 mg/g Cr at the baseline to 301+/
      111 mg/g Cr at the end of the study, while UAE remained unchanged, 81+/-15 mg/g
      Cr at the baseline and 87+/-19 mg/g Cr at the end of the study, in the epalrestat
      treated group. Reciprocal creatinine measured by an enzyme assay decreased
      significantly (P<.01) in both groups; however, the reduction rate in the
      epalrestat-treated group was significantly (P<.05) smaller than that in the
      control group. These results suggest the potential usefulness of ARIs in
      preventing the progression of incipient diabetic nephropathy in patients with
      type 2 diabetes mellitus.

PMID- 11522495
TI  - The effects of HDV-insulin on carbohydrate metabolism in Type 1 diabetic
      patients.
AB  - The aim of this study was to compare the metabolic effects of a single equimolar
      subcutaneous injection of hepatic directed vesicle-insulin (HDV-insulin) and
      regular insulin on glucose levels and intermediary metabolism during a 75-g oral
      glucose tolerance test (OGTT). Nine Type 1 diabetic patients underwent two
      experiments separated by 4 weeks. Each experimental protocol consisted of an
      identical evening meal followed by overnight euglycemic control achieved by a
      continuous low-dose insulin infusion. The next morning a subcutaneous injection
      (0.1 U/kg) of HDV-insulin or regular insulin was administered 30 min before a 75
      g OGTT. The overnight basal insulin infusion was maintained unaltered throughout
      the 150-min OGTT. Plasma glucose, glucoregulatory hormones (insulin, glucagon,
      cortisol), and intermediary metabolites (lactate, alanine, glycerol, NEFA, beta
      hydroxybutyrate) were measured to assess the metabolic effects of the two insulin
      preparations. Compared to regular insulin, an equivalent subcutaneous dose of HDV
      insulin significantly lowered glucose levels during OGTT (mean reduction 2.2+/
      0.4 mmol/l; P<.005). Plasma levels of insulin and glucagon were equivalent during
      both series of experiments. Blood lactate, glycerol and plasma NEFA levels were
      not different during OGTT indicating similar peripheral action of the insulins.
      beta-Hydroxybutyrate levels were significantly reduced (P<.05) following HDV
      insulin supporting a preferential hepatic action of the preparation. We conclude
      that HDV-insulin can significantly lower plasma glucose excursions compared to an
      equivalent dose of regular insulin during an OGTT in Type 1 diabetic patients.
      The metabolic profile of equivalent peripheral insulin, glucagon and glycerol
      levels but reduced beta-hydroxybutyrate values support a hepatospecific effect of
      HDV-insulin.

PMID- 11522498
TI  - Secretion of GIP in responders to acarbose in obese Type 2(NIDDM) patients.
AB  - Acarbose has been shown to reduce postprandial hyperglycemia and to improve lipid
      parameters in diabetics via its inhibitory effects on intestinal alpha
      glucosidases. Response to acarbose may therefore be dependent upon gastric or
      pancreatic hormone function. To test this hypothesis, we treated 27 mild type 2
      (NIDDM) Japanese diabetics who were mildly obese with low-dose acarbose (150
      mg/day) for 3 months. We then performed a responder analysis to determine
      specific hormonal responses that may be associated with a good response to
      acarbose. At the end of the treatment period, a total of 15 evaluable patients
      was grouped as responders (n=6) and nonresponders (n=9) based on an effective
      decrease in postprandial glucose levels (>30 mg/day) and glycosylated hemoglobin
      (HbA1c) levels (>0.5%). There were no differences between the two groups in
      demographic variables or mean postprandial glucose levels at baseline. There was
      a small but significant increase in postprandial cholecystokinin (CCK) in
      responders, and fasting gastric inhibitory peptide (GIP) levels were
      significantly increased in responders and all patients after treatment. Serum
      leptin levels were reduced by treatment in our mildly obese responders and this
      was associated with a significant decrease in body weight. These results suggest
      that treatment with low-dose acarbose may reduce hyperglycemia in mild type 2
      Japanese patients and may improve metabolic control by regulating hormones
      involved in glycemic control and digestive absorption. Acarbose may provide a
      safe adjunct to help treat insulin resistance in type 2 patients.

PMID- 11522499
TI  - Follow-up of plasma semicarbazide-sensitive amine oxidase activity and
      retinopathy in Type 2 diabetes mellitus.
AB  - Plasma activity of the enzyme semicarbazide-sensitive amine oxidase (SSAO) is
      high in diabetes. Production of angiotoxic substances (an aldehyde, hydrogen
      peroxide, and ammonia) in vessel walls is catalysed by SSAO, suggesting a role
      for SSAO in the development of complications of diabetes. The objective of the
      present study was to follow up plasma SSAO activity (measured radiometrically),
      HbA(1c) (using ion exchange chromatography), and retinopathy (by fundus
      photography) after 2.8 years, in 34 patients with Type 2 diabetes. We also
      measured urinary levels of an SSAO substrate, methylamine, by fluorometric high
      performance liquid chromatography (HPLC). As at baseline, plasma SSAO activity
      was now higher in subjects with retinopathy (mean 19.5) than in subjects without
      retinopathy (mean 16.0), 95% confidence interval (CI) for difference 0.6-6.3 nmol
      benzylamine ml(-1) plasma h(-1). SSAO activity had not changed significantly
      since baseline, mean difference -1.65 and 95% CI for difference -3.76 to 0.46
      nmol benzylamine ml(-1) plasma h(-1). Mean HbA(1c) level remained higher for
      patients with retinopathy (now 7.9%) compared to those without retinopathy
      (6.1%), 95% CI for difference 0.6-3.0%. Comparing baseline and the present study,
      retinopathy was nonproliferative; level had worsened for five and improved for
      two patients. Urinary methylamine/creatinine ratio was lower in the group of
      patients with retinopathy (mean 0.99) than in those without retinopathy (mean
      1.78), 95% CI for difference 0.1-1.5 microg mg(-1). The results of the present
      study are compatible with a role for SSAO in the development of diabetic
      retinopathy.

PMID- 11522500
TI  - Inflammatory cytokines in vitreous fluid and serum of patients with diabetic
      vitreoretinopathy.
AB  - To determine whether inflammatory cytokines are increased in proliferative
      diabetic retinopathy. We measured concentrations of interleukin-6, 8 (IL-6, 8)
      and tumor necrosis factor (TNF)-alpha by enzyme-linked immunosorbent assay
      (ELISA) in vitreous and serum from 47 patients with proliferative diabetic
      retinopathy and 21 patients with vitreous noninflammatory retinopathies. Vitreous
      concentration of IL-6 were 64.7+/-12.8 pg/ml in proliferative diabetic
      retinopathy, much greater (P<.005) than in noninflammatory retinopathy (2.8+/-4.5
      pg/ml). Amounts of IL-8 in vitreous fluid also were greater in proliferative
      retinopathy than in noninflammatory retinopathy (34.0+/-11.5 vs. 6.1+/-2.0 pg/ml,
      P<.005). Concentrations of TNF-alpha in vitreous fluid were not statistically
      different in proliferative retinopathy from those in noninflammatory retinopathy.
      In sera, concentrations of IL-6 and IL-8 were not different between proliferative
      and noninflammatory retinopathy. However, serum TNF-alpha was much greater in
      proliferative retinopathy than in noninflammatory retinopathy (0.81+/-0.72 vs.
      0.09+/-0.00 pg/ml, P<.001). Elevated TNF-alpha in serum then may be
      diagnostically useful in proliferative diabetic retinopathy. And inflammatory
      cytokines in vitreous may be pathogenically important in this concentration.

PMID- 11522501
TI  - Skin temperature in the neuropathic diabetic foot.
AB  - Several authors have reported higher skin temperature in the feet of diabetic
      subjects with autonomic neuropathy. We reexamined this association in a cross
      sectional study of 712 veterans with diabetes mellitus. Potential subjects
      included all diabetic patients enrolled in a general internal medicine clinic at
      a veterans affairs healthcare system. Sensory neuropathy was defined as any pedal
      insensitivity to the 5.07 monofilament. Autonomic neuropathy was determined using
      standard cardiovascular reflex tests. An infrared surface scanner was used to
      measure foot skin temperature at multiple sites. Subjects with sensory neuropathy
      had lower mean plantar foot skin temperature than those without (28.4 degrees C
      vs. 28.9 degrees C, P=.0101). Autonomic neuropathy as a dichotomous variable was
      unrelated to foot skin temperature. Foot skin temperature, though, negatively
      correlated with greater drop in systolic blood pressure with standing, which is
      an indicator of autonomic neuropathy (r=-.08, P=.0385). Adjustment for potential
      confounding factors using multiple linear regression analysis resulted in
      diminution of the associations between foot skin temperature and sensory
      neuropathy or orthostatic blood pressure drop, but the latter association
      remained statistically significant in the right foot. Diabetic veterans with
      sensory or autonomic neuropathy do not have higher foot skin temperature. Our
      results suggest that skin temperature may be slightly lower with higher
      orthostatic blood pressure fall. Other causes exist for the frequently observed
      differences in skin temperature in the feet of diabetic subjects.

PMID- 11522502
TI  - Clinical evaluation of plasma high-density lipoprotein subfractions (HDL2, HDL3)
      in non-insulin-dependent diabetics with coronary artery disease.
AB  - STATEMENT OF THE PROBLEM: Low levels of high-density lipoprotein cholesterol (HDL
      C) have a strong association with coronary artery disease (CAD) in patients with
      non-insulin-dependent diabetes mellitus (NIDDM). In this study, we tried to
      evaluate whether one or both of the major HDL subclasses (HDL2, HDL3) is strongly
      associated with the risk of CAD in NIDDM subjects. METHODS: The separation of HDL
      subclasses was carried out by ultracentrifugation in a Beckman Airfuge. HDL2
      subclass was isolated from the supernatant and its cholesterol content was
      measured enzymatically. Plasma HDL3 cholesterol was calculated as the difference
      between results for total HDL cholesterol and HDL2 cholesterol. RESULTS: NIDDM
      patients with CAD had significantly higher triglyceride levels compared to either
      control (217.09+/-55.04 versus 89.62+/-31.29 mg/dl, P=.001) or CAD patients
      without NIDDM (217.09+/-55.04 versus 156.28+/-46.39 mg/dl, P<.05). However, in
      the diabetic patients with CAD, there was a statistically significant decrease in
      HDL cholesterol (39.63+/-8.59 versus 55.86+/-13.49 mg/dl, P<.01), HDL2
      cholesterol (8.74+/-3.28 versus 16.95+/-5.73 mg/dl, P<.001), and HDL3 cholesterol
      (31.23+/-7.41 versus 38.91+/-8.93 mg/dl, P<.05) in comparison to nondiabetic
      controls. Moreover, in the comparison between non-insulin-dependent diabetics
      with CAD and CAD subjects without NIDDM, HDL cholesterol (39.63+/-8.59 versus
      46.13+/-6.33 mg/dl, P<.05) and HDL2 cholesterol (8.74+/-3.28 versus 11.84+/-4.01
      mg/dl, P<.02) were significantly reduced, while HDL3 cholesterol levels were
      (31.23+/-7.41 versus 34.29+/-7.94 mg/dl, P=.92) unaltered. Additionally, the
      percentage reduction of cholesterol in HDL2 fraction was proportionately greater
      than the decrease in HDL3 subclass in both comparisons. Moreover, in NIDDM with
      CAD, HDL cholesterol was reduced by 29% and 14%, HDL2 cholesterol by 48% and 26%,
      and HDL3 cholesterol by 20% and 9%, compared relatively to controls and CAD
      subjects without NIDDM. CONCLUSIONS: In conclusion, HDL2 is the more variable
      subclass and reflects changes in HDL. This suggests that the protective role of
      total HDL against CAD is mainly mediated through HDL2 fraction. Therefore, HDL2
      might be a better predictor of coronary heart disease than total HDL, in non
      insulin-dependent diabetes mellitus.

PMID- 11522503
TI  - Serum lipoprotein(a) concentration as a cardiovascular risk factor in Kuwaiti
      type 2 diabetic patients.
AB  - Serum lipoprotein(a) [Lp(a)], a risk factor for coronary heart disease (CHD) in
      some nondiabetic populations, is largely under genetic control and varies among
      ethnic and racial groups. We evaluated serum Lp(a) concentration and its
      relationship with traditional CHD risk factors (age, sex, smoking, hypertension,
      dyslipidemia) as well as stage of diabetic nephropathy in 345 type 2 diabetic
      patients. Lp(a) concentration was skewed with median (2.5th, 97.5th percentiles)
      of 25.0 (8.1, 75.7) mg/dl. Twenty-three of 55 (41.8%) patients with CHD had
      increased (>30 mg/dl) Lp(a) compared with 102 of 290 (35.1%) patients without CHD
      (P=.35). Twelve of 27 (44.4%) female patients with CHD had increased Lp(a)
      compared to 11 of 28 (39.3%) males (P=.70). Lp(a) was significantly (P<.05)
      higher in females than males, but the logistic regression analysis showed
      significant association of Lp(a), LDL-C, and duration of diabetes mellitus (DM)
      with CHD in male patients only. Although female patients with CHD and
      macroalbuminuria had significantly (P<.05) higher Lp(a) than normoalbuminuric
      female patients without CHD, no such association was found in males and no
      significant association was found between Lp(a) and the degree of albuminuria.
      Partial correlation analysis controlling for age, sex, and BMI showed significant
      correlation of Lp(a) with total cholesterol only (P=.03) and no correlation was
      found with other lipid parameters. Multiple regression analysis did not show
      significant associations of Lp(a) with standard CHD risk factors, HbA(1c), and
      plasma creatinine. This study is in agreement with studies in other populations,
      which showed that Lp(a) may not be an independent risk factor for CHD in patients
      with DM. However, as Lp(a) could promote atherogenesis via several mechanisms,
      follow-up studies in our patients will confirm if increased Lp(a) concentration
      can partly account for the poorer prognosis when diabetic patients develop CHD.

PMID- 11522504
TI  - Type 1 diabetes with no diabetic complications, 62 years later.
AB  - We report a type 1 diabetes in an 88-year-old female patient discovered in 1938
      at the age of 26. She was promptly put on insulin, which lasted 62 years so far.
      This patient was highly remarkable because she portrayed a historical case of
      insulin-treated diabetes diagnosed in 1938. The absence of microangiopathy and
      specially retinopathy was quite singular, all the more reason that her diabetes
      was ill-controlled. Environmental or genetic factors may, one day, explain this
      unusual favourable outcome.

PMID- 11522505
TI  - Are we building good relationships?

PMID- 11522506
TI  - Bacteriophages: a rich store of new antibiotics?

PMID- 11522507
TI  - Milking nature for Alzheimer's treatment.

PMID- 11522508
TI  - Measles vaccine could treat lymphoma.

PMID- 11522511
TI  - Private prescription: The age of peers.

PMID- 11522512
TI  - Can smart bullets penetrate magic bullet-proof vests?

PMID- 11522513
TI  - Virogenomics: the future looks bright.

PMID- 11522514
TI  - Careful selection of physicians is required to allay public fears in clinical
      trials.

PMID- 11522515
TI  - Beyond the genome: turning data into knowledge.
AB  - Since the publication of the draft sequence of the human genome in April 2001
      (1,2), the pressure on life scientists to annotate and gain useful knowledge from
      the millions of As, Gs, Cs and Ts, is ever increasing. Now that the initial hype
      has passed, the life sciences field demands the technologies and computer power
      that can produce and analyze data in a high-throughput manner for drug discovery
      and disease diagnosis. Cambridge Healthtech Institute's Beyond Genome 2001
      conference(1) (17-22 June 2001, San Francisco, CA, USA) brought together the
      latest research in these technologies in a 'tri-conference' that encompassed the
      10th Annual Conference of Bioinformatics and Genome Research, the 3rd Annual
      Conference of In Silico Biology and the 5th Annual Conference of Proteomics.

PMID- 11522516
TI  - Understanding GPCRs - from orphan receptors to novel drugs.

PMID- 11522517
TI  - Finding drug targets in microbial genomes.
AB  - In this era of genomic science, knowledge about biological function is integrated
      increasingly with DNA sequence data. One area that has been significantly
      impacted by this accumulation of information is the discovery of drugs to treat
      microbial infections. Genome sequencing and bioinformatics is driving the
      discovery and development of novel classes of broad-spectrum antimicrobial
      compounds, and could enable medical science to keep pace with the increasing
      resistance of bacteria, fungi and parasites to current antimicrobials. This
      review discusses the use of genomic information in the rapid identification of
      target genes for antimicrobial drug discovery.

PMID- 11522518
TI  - Delivery systems for DNA-binding drugs as gene expression modulators.
AB  - Despite the large number of publications describing the synthesis and
      physicocharacterization of the binding between drugs and DNA, relatively few
      examine drug delivery systems (DDSs) for these molecules. The aim to find DDSs
      for DNA-binding drugs (DBDs) was prompted mainly to reduce the toxicity and/or
      enhance the tumor specificity of systemically administered drugs. With this in
      mind, we have reviewed the biological effects of some DBDs that are currently
      used as antitumor drugs and describe a brief selection of DDSs currently in
      clinical trials or on the market.

PMID- 11522519
TI  - Ion-exchange resins: carrying drug delivery forward.
AB  - Ion-exchange resins (IER), or ionic polymer networks, have received considerable
      attention from pharmaceutical scientists because of their versatile properties as
      drug-delivery vehicles. In the past few years, IER have been extensively studied
      in the development of novel drug-delivery systems (DDSs) and other biomedical
      applications. Some of the DDSs containing IER have been introduced into the
      market. In this review, the applications of IER in drug delivery research are
      discussed.

PMID- 11522520
TI  - Monitor: molecules and profiles.

PMID- 11522521
TI  - Novel antitumour molecules.

PMID- 11522522
TI  - Learned helplessness in the rat: improvements in validity and reliability.
AB  - Major depression has a high prevalence and a high mortality. Despite many years
      of research little is known about the pathophysiologic events leading to
      depression nor about the causative molecular mechanisms of antidepressant
      treatment leading to remission and prevention of relapse. Animal models of
      depression are urgently needed to investigate new hypotheses. The learned
      helplessness paradigm initially described by Overmier and Seligman [J. Comp.
      Physiol. Psychol. 63 (1967) 28] is the most widely studied animal model of
      depression. Animals are exposed to inescapable shock and subsequently tested for
      a deficit in acquiring an avoidance task. Despite its excellent validity
      concerning the construct of etiology, symptomatology and prediction of treatment
      response [Clin. Neurosci. 1 (1993) 152; Trends Pharmacol. Sci. 12 (1991) 131]
      there has been little use of the model for the investigation of recent theories
      on the pathogenesis of depression. This may be due to reported difficulties in
      reliability of the paradigm [Animal Learn. Behav. 4 (1976) 401; Pharmacol.
      Biochem. Behav. 36 (1990) 739]. The aim of the current study was therefore to
      improve parameters for inescapable shock and learned helplessness testing to
      minimize artifacts and random error and yield a reliable fraction of helpless
      animals after shock exposure. The protocol uses mild current which induces
      helplessness only in some of the animals thereby modeling the hypothesis of
      variable predisposition for depression in different subjects [Psychopharmacol.
      Bull. 21 (1985) 443; Neurosci. Res. 38 (200) 193]. This allows us to use animals
      which are not helpless after inescapable shock as a stressed control, but
      sensitivity, specificity and variability of test results have to be reassessed.

PMID- 11522523
TI  - Quantitative in situ hybridization for peptide mRNAs in mouse brain.
AB  - The objective was to determine the feasibility of using a radioactive capture
      method (Fuji FLA 2000) and image analysis system for the measurement of peptide
      mRNA levels in specific brain regions in mice. As a test mRNA, we chose
      vasopressin (VP) and oxytocin (OT) because they are expressed in abundance in the
      hypothalamic paraventricular (PVN) and supraoptic nuclei (SON). A comparison was
      made between free-floating and slide-mounted sections to determine which method
      yielded better results. Mouse brains were fixed in 4% paraformaldehyde (PFA) and
      processed for in situ hybridization using 35S-oligonucleotide probes for VP and
      OT. After overnight hybridization and high stringency washes, 25-microm brain
      sections and 14C standards were exposed to a BAS-IIIs Fuji imaging film over a
      range of times (4 h-6 days). Results showed that there was an intense
      hybridization reaction in the PVN and SON, making it possible to distinguish the
      specific brain regions. Using Image Gauge Software, the signal was quantified in
      PVN and SON. A comparison of the different exposure times showed that the signal
      could be measured after as little as 4 h. The intensity readings increased over
      time while the calculated radioactivity remained constant. The free-floating
      method was superior to the slide-based system, providing a lower background and a
      higher signal. The data illustrates the applicability of the phosphor imaging
      system for the reproducible measurement of mRNA levels in discrete regions of the
      mouse brain.

PMID- 11522524
TI  - Wavelet Transform in the analysis of the frequency composition of evoked
      potentials.
AB  - This technical paper deals with the application of the Wavelet Transform to the
      study of evoked potentials. In particular, Wavelet Transform gives an optimal
      time-dependent frequency decomposition of the evoked responses, something
      difficult to be achieved with previous methods such as the Fourier Transform. We
      describe in detail the protocol for implementing the decomposition based on the
      Wavelet Transform and apply it to two different types of evoked potentials. In
      the first case we study alpha responses in pattern visual evoked potentials and
      in the second case, we study gamma responses to bimodal (auditory and visual)
      stimulation. Although in this study we focus on methodological issues, we briefly
      discuss physiological implications of the present time-frequency analysis.
      Furthermore, we show examples of the better performance of the wavelet
      decomposition in comparison with Fourier-based methods.

PMID- 11522525
TI  - Determination of tetrahydrobiopterin in murine locus coeruleus by HPLC with
      fluorescence detection.
AB  - Tetrahydrobiopterin in the murine locus coeruleus was measured as its fully
      oxidized form, biopterin, using a HPLC coupled to a fluorescence detector,
      because tetrahydrobiopterin itself cannot be detected by such means. The
      differential oxidization method distinguished tetrahydrobiopterin-derived
      biopterin and dihydrobiopterin-derived biopterin. The protocol reported here is a
      rapid and sensitive method that facilitates the measurement of tissue and/or
      cellular tetrahydrobiopterin. Using this assay protocol, we were able to detect
      and quantify variations in the tetrahydrobiopterin content in the murine locus
      coeruleus.

PMID- 11522526
TI  - Methods for quantification of in situ hybridization signals obtained by film
      autoradiography and phosphorimaging applied for estimation of regional levels of
      calmodulin mRNA classes in the rat brain.
AB  - Comparative analysis of the regional abundances of the various mRNAs in neural
      tissues requires the quantitation of target nucleic acid sequences while their
      tissue distribution is preserved. A quantitative in situ hybridization protocol
      is presented for the assessment of regional levels of calmodulin (CaM) I, II and
      III mRNAs in the rat brain. Coronal brain cryostat sections were hybridized with
      multiple CaM [35S]cRNA probes and co-exposed to an autoradiographic film or
      storage phosphor screen, together with a membrane-based radioactive standard
      scale. The membrane scale was calibrated against a brain paste standard scale.
      Regression analyses of the sensitometric graphs of standard scales corresponding
      to the autoradiographic film and to the storage phosphor screen were performed by
      means of exponential (ROD=p(1)(1-exp[-p(2)x])) and linear (LI=ax) functions,
      respectively (ROD is relative optical density, LI is labeling intensity, and x is
      radioactivity). The ROD/LI values for the hybridized brain regions were converted
      into cRNA probe copy numbers (estimations of mRNA copy numbers) through use of
      the above standard scales. This method was applied to compare the regional
      abundances of multiple CaM mRNAs in the brains of control, dehydrated, chronic
      ethanol-treated and ethanol withdrawal-treated animals.

PMID- 11522527
TI  - A simple stereologic method for analysis of cerebral cortical microvessels using
      image analysis.
AB  - Previous methods for determining morphological features of vascular networks in
      cerebral cortex were subject to arbitrary variation and bias. Unbiased estimates
      of vessel number, volume, surface area and length can be obtained using
      stereology but these techniques tend to be tedious and time-consuming.
      Stereologic protocols generally require micrographs that have to be analyzed
      manually for intersections of vessels on grid points or lines. In this report, we
      provide a simpler and more precise method for measuring morphological features of
      cerebral cortical microvessels. Images of microvessels in 1 microm toluidine blue
      stained sections were captured using a popular image analysis software package.
      Luminal surfaces of endothelial cells were automatically traced using commonly
      available features; the two-dimensional data of vessels (diameter, area,
      perimeter and number of vessels) were automatically computed and transferred to a
      spreadsheet. Three-dimensional features were then determined using basic
      stereologic equations. The method eliminates the need for manual measurements and
      is particularly time- and cost-effective for quantitative studies where numerous
      images have to be evaluated.

PMID- 11522528
TI  - Holger Hyden's technique of preparation of single Deiters' neurons and study of
      permeability characteristics of their plasma membranes.
AB  - The protocols described here refer to Hyden's technique of isolation and
      microdissection of vestibular Deiters' neurons from adult mammals. The isolation
      of Deiters' cells from bovine is described and an example is given of the
      immunocytochemical visualization of their GABA(A) receptors by monoclonal
      antibodies against the beta(2/3) subunit. In addition, the protocol of the method
      for isolation of Deiters' cells from adult rabbit brain stem, the preparation of
      their plasma membranes and the study of their permeability characteristics is
      presented. Also in this case, examples of its application to the determination of
      chloride permeability and its modulation by GABA are given.

PMID- 11522529
TI  - Hypothalamic neuroactivity in specific processes and central regulation of body
      temperature and water intake.
AB  - The method described was designed to elucidate the role of a particular neuronal
      system or specific nucleus in the central nervous system (CNS) in controlling
      physiological and biological functions. The neurochemical aspects of the CNS
      regulatory mechanism and related networks remain to be further investigated.
      There is little information available about the relationship between
      neuroactivity in the specific brain nuclei and physiological or biological
      responses in mammals. An adequate analysis of this relationship provides valuable
      insight to clarify which nucleus and what types of neurons are truly involved in
      the excitation of physiological events and its regulation. In the present study,
      we used microdialysis for stimulation of the anterior hypothalamus (AH) and
      simultaneous analysis of cholinergic activity, and we investigated c-Fos-like
      immunoreactivity (Fos-IR) in the brain in the same animal following
      microdialysis. The nuclear protein c-Fos, the product of c-fos oncogene, has been
      used as a marker of neuronal activity at the cellular level in the brain. Various
      physiological and pharmacological stimuli have been shown to induce Fos-IR in
      specific neuronal populations located in various regions of the brain. However,
      there are few studies investigating the responses produced by c-Fos expression in
      specific regions in same animals. We showed the involvement of hypothalamic
      cholinergic mechanisms in the thermoregulatory and water regulatory processes
      using the above procedures.

PMID- 11522530
TI  - Procedure of bidirectional selective outbreeding for production of two rat lines
      differing in sensitivity to the sedative/hypnotic effect of gamma-hydroxybutyric
      acid.
AB  - The exogenous administration of gamma-hydroxybutyric acid (GHB), a constituent of
      the mammalian brain where it likely functions as a neurotransmitter or a
      neuromodulator, exerts a number of pharmacological effects, including sedation
      and hypnosis. The present paper describes a procedure for selective breeding of
      two rat lines which markedly differ in sensitivity to the sedative/hypnotic
      effect of GHB. Selective breeding originated from Wistar rats showing opposite
      sensitivity to the sedative/hypnotic effect of 1 g/kg GHB (i.p.). 'Sensitive'
      Wistar rats, defined as those individuals displaying values of r = sleep
      time/onset greater than the upper 15th percentile, were mated to generate the GHB
      sensitive (GHB-S) line; conversely, 'resistant' Wistar rats (r-values lower than
      the lower 15th percentile) were mated to generate the GHB-resistant (GHB-R) line.
      Upper and lower 15th percentiles were also used to establish the selection cut
      offs and criteria for rats of subsequent generations. Specifically, r-values of
      GHB-S rats were required to be r > or =8 on two separate tests with GHB; r-values
      of GHB-R rats were required to be r < or =2 on two separate tests with GHB. In
      each of the three generations produced to date, GHB-S rats showed significantly
      shorter onset, longer sleep times and greater r-scores than GHB-R rats. The
      selective breeding of GHB-S and GHB-R rats: (a) suggests that sensitivity to GHB
      is under genetic control, and (b) may constitute a unique model for investigation
      of the physiological function of GHB.

PMID- 11522531
TI  - A method to monitor corticomotor excitability during passive rhythmic movement of
      the upper limb.
AB  - A procedure is outlined in which the excitability of the corticomotor pathway is
      examined during rhythmic, passive upper limb movement. Using a custom built
      apparatus and software, wrist flexion-extension movements of a programmable
      frequency, amplitude and duration are induced while transcranial magnetic stimuli
      are delivered to the contralateral cortex over the area representing the flexor
      carpi radialis muscle. Stimuli are timed to occur during different phases of the
      movement cycle in order to examine the influence of ascending sensory input on
      the excitability of the corticospinal pathway. The protocol enables modulations
      in evoked responses to be analysed during movement of different frequencies and
      amplitudes, and permits alterations in cortical excitability to be examined by
      using paired pulse paradigms. The technique may also be utilised to examine
      hemispheric and segmental transfer if a stationary target limb is probed while
      the contralateral limb is passively moved. The protocol has potential use in
      examining corticomotor excitability in subjects with deficits in sensory and/or
      motor function, such as patients with Parkinson's disease or individuals
      recovering from stroke.

PMID- 11522532
TI  - Detection of the exogenous hGDNF in gerbils under the treatment with AxCAhGDNF
      adenoviral vector.
AB  - Glial cell line-derived neurotrophic factor (GDNF) is one of the most potent
      neurotrophic factors and promotes survival in many populations of cells. We
      examined the neuroprotective effect of an adenoviral vector encoding glial cell
      line-derived neurotrophic factor (AxCAhGDNF) on the transient global ischemia
      [Brain Res. 885 (2000) 273-282]. Gerbils received AxCAhGDNF or an adenoviral
      vector encoding bacterial beta-galactosidase gene (AxCALacZ) through
      administration into the lateral ventricle. Two days later, occlusion of the
      common carotid arteries for 5 min bilaterally using aneurysm clips produced
      transient global forebrain ischemia. Animals showed intense immunolabeling for
      GDNF in ependymal cells on 2, 4 and 7 days after the operation. The exogenous
      gene transducted by the adenovirus in the same cells was detected by in situ
      hybridization. The treatment with AxCAhGDNF significantly prevented the loss of
      hippocampal CA-1 pyramidal neurons 2 to 7 days after the operation, as compared
      to AxCALacZ treatment. Also terminal deoxynucleotidyl transferase-mediated dUTP
      biotin in situ nick end labeling (TUNEL) staining was markedly reduced in the
      case with AxCAhGDNF treatment at 7 days after the operation. In this paper, we
      describe in detail the techniques for the detection of the exogenous gene of
      hGDNF under the treatment with AxCAhGDNF.

PMID- 11522533
TI  - Designing clinical trials on gastric lymphomas and reporting outcomes.

PMID- 11522534
TI  - Post-transcriptional effects of interleukin-3, interferon-gamma, erythropoietin
      and butyrate on in vitro hemoglobin chain synthesis in congenital hemolytic
      anemia.
AB  - BACKGROUND AND OBJECTIVES: Various agents modulate hemoglobin synthesis. In vitro
      modulation of translation in hemoglobin chain synthesis was analysed in patients
      with congenital hemolytic anemia (n=32) and healthy controls (n=17). DESIGN AND
      METHODS: Enriched reticulocytes were co-incubated with (3)H-leucine and cytokines
      or butyrate. Reversed-phase chromatography enabled separation of alpha-, beta-
      and gamma-globin chains. Globin chain synthesis was calculated from measured (3)H
      leucine incorporation. Transferrin, erythropoietin, interleukin-3 and interferon
      gamma receptors were detected by flow cytometry. Reverse-transcription polymerase
      chain reaction (RT PCR) was used to demonstrate changes of RNA stability. RESULTS
      AND DISCUSSION: Interleukin-3, interferon-gamma and butyrate caused a significant
      2-fold increase (range 1.8-2.4; p<0.01) of the alpha- and beta-chain synthesis in
      congenital hemolytic anaemias. Analysis of gamma-globin chain synthesis revealed
      a lower, i.e. 1.4 fold increase (range 1.32 to 1.41; p<0.03). The absolute amount
      of globin synthesis was calculated to be 2.9 x 10(-12) g/reticulocyte/24h. After
      incubation with interleukin-3 the absolute additional synthesis of the alpha
      globin chain reached 1.31 x 10(-12) g/reticulocyte/24h, of the beta-globin chain,
      1.15 x 10(-12) g/reticulocyte/24h and of the gamma-globin chain, 0.26 x 10(-12)
      g/reticulocyte/24h. Butyrate and interferon-gamma had no or even an inhibiting
      effect on reticulocytes from normal controls, while interleukin-3 stimulated
      alpha- and gamma-chain synthesis (1.4 and 2.4 fold, respectively; p<0.03)
      suggesting an increase of fetal hemoglobin (HbF). Erythropoietin showed no
      stimulating influence. Membrane associated interleukin-3 receptors were detected
      in 0.78+/-0.14%, and interferon-gamma receptors in 0.1+/-0.015% of the red cells.
      Erythropoietin receptors were extremely rare (0.05+/-0.015%). The expression of
      transferrin receptors (CD71) correlated with the extent of globin chain
      stimulation. The alpha-, and beta-globin mRNA content of the reticulocytes after
      interleukin-3 incubation, as measured by RT-PCR, increased. INTERPRETATION AND
      CONCLUSIONS: Hemoglobin chain synthesis could be modulated post-transcriptionally
      by interleukin-3, interferon-gamma and butyrate. Transferrin receptor and globin
      RNA stability might be involved in this phenomenon.

PMID- 11522535
TI  - Aberrant phenotypes in acute myeloid leukemia: a high frequency and its clinical
      significance.
AB  - BACKGROUND AND OBJECTIVES: Immunophenotyping is an essential method for diagnosis
      and classification of acute myeloid leukemias (AML), and its extensive use could
      identify blast cell subpopulations with aberrant phenotypes rarely seen in normal
      myelopoiesis. The aberrant phenotypes have been correlated with clinical,
      morphological and prognostic features but their occurrence in AML differs in the
      various studies. DESIGN AND METHODS: In this study, we analyzed 35 cases of AML,
      examining them for aberrant phenotypes by multiparametric flow cytometry. Co
      expression of lymphoid-associated markers in myeloblasts and asynchronous antigen
      expression were correlated with clinical features. RESULTS: Aberrant phenotypes
      were found in 88.6% of the cases studied. In this group, cross-lineage antigen
      expression was present in 34.3% and asynchronous expression in 82.4% of the
      cases. CD7 was the most frequent lymphoid-associated antigen. Among the cases of
      asynchronous antigen expression, the most frequent phenotype was CD117(+) and/or
      CD34(+) in association with CD11c(+), followed by CD15(+) and CD65(+),
      corresponding to 67.6%, 61.7 and 50.0% of the cases, respectively. Twenty out of
      33 patients were available for complete remission assessment. The CD117(+)
      CD15(+) phenotype correlated significantly with complete remission achievement
      and with the lack of unfavorable chromosome associations. INTERPRETATION AND
      CONCLUSIONS: We conclude that aberrant phenotypes, as they are described here,
      are present in the great majority of cases of AML, asynchronous antigen
      expression being the most frequent example; and that CD117(+) CD15(+) phenotype
      shows a relevant association with clinical prognosis.

PMID- 11522536
TI  - Additional cytogenetic changes do not influence the outcome of patients with
      newly diagnosed acute promyelocytic leukemia treated with an ATRA plus
      anthracyclin based protocol. A report of the Spanish group PETHEMA.
AB  - BACKGROUND AND OBJECTIVES: To analyze in patients with de novo acute
      promyelocytic leukemia (APL) treated with an ATRA plus anthracyclin-based
      protocol if the presence of additional cytogenetic aberrations to the t(15;17)
      influences: 1. clinical and biological presenting features; 2. disease outcome.
      DESIGN AND METHODS: One hundred and thirteen patients with newly diagnosed APL
      enrolled in the APL-96 protocol of the Spanish PETHEMA group were studied by
      conventional karyotyping, FISH and RT-PCR for the PML-RARa fusion. Treatment was
      homogeneous in all cases and consisted of anthracyclines and ATRA. RESULTS:
      Additional chromosome aberrations were observed in 30% of cases. The most
      frequent secondary changes were +8 (14 cases), and abnormalities of chromosomes 9
      or 3 (4 patients each), and of chromosomes 1 and 8 (3 cases each). No clinical,
      biological, morphological, immunophenotypic or molecular differences were
      observed between the group of APLs with t(15;17) alone and the group of patients
      with additional changes. Patients with additional changes had a higher rates of
      complete remission (CR) and 4-year disease-free survival (DFS) (97%, and 97%,
      respectively) than patients with t(15;17) alone (CR, 70% and DFS, 84%) but these
      differences were not statistically significant. INTERPRETATION AND CONCLUSIONS:
      Patients with APL and additional cytogenetic abnormalities do not show different
      clinical, biological, morphological or molecular features as compared to patients
      with t(15;17) alone. The prognosis of patients with APL and t(15;17) alone and
      those with additional changes is similar in both groups. This study indicates
      that there is no rationale for administering more intensive treatment in APL
      patients with additional cytogenetic abnormalities receiving ATRA plus
      anthracycline-based chemotherapy.

PMID- 11522537
TI  - Aggressive salvage treatment is not appropriate for the majority of elderly
      patients with acute myeloid leukemia relapsed from first complete remission.
AB  - BACKGROUND AND OBJECTIVES: The prognosis of acute myeloid leukemia (AML) in the
      elderly is still poor because of different reasons, including a high incidence of
      relapse. The aim of this study was to investigate whether aggressive salvage
      chemotherapy (CHT) results in an actual survival advantage in elderly patients
      with relapsed AML, as well as to compare hospitalization and load of supportive
      treatment between patients receiving aggressive management or only palliation.
      DESIGN AND METHODS: One hundred and fifty consecutive patients with relapsed AML
      (median age 66 years) were analyzed. At relapse, 99 (66%) were treated with CHT,
      and 51 had palliative management. RESULTS: Second complete remission (CR2) was
      achieved in 36/99 patients (36%) receiving CHT, while no CR was observed in the
      other group (p<0.001). Induction death rate was 22%, while 41% were resistant to
      CHT. The median survival from relapse was 4 months for the whole patient
      population; according to management, it was 5 months and 3 months for CHT and
      palliation, respectively (p=0.01). As to patients given CHT, a CR1 duration of
      more than 12 months was the only parameter significantly related to a better
      clinical outcome (survival from relapse: 8 vs. 4 months, p=0.002; CR2 duration:
      11 vs. 5 months, p=0.001, respectively). Finally, patients managed with
      palliation required less hospitalization and less supportive therapy as compared
      to the CHT group. INTERPRETATION AND CONCLUSIONS: Aggressive chemotherapy results
      in an actual survival advantage only for a minority of elderly patients with
      relapsed AML, i.e. those with CR1 lasting for more than 12 months.

PMID- 11522538
TI  - Emotional and behavioral symptoms in children with acute leukemia.
AB  - BACKGROUND AND OBJECTIVES: The diagnosis of leukemia is probably one of the most
      severe stressors that children can experience and may be associated with
      emotional and behavioral symptoms indicating comorbidity with mental health
      disorders. This study aims to evaluate the presence of emotional and behavioral
      symptoms in children with acute leukemia exposed to chemotherapy from outpatient
      services at two university hospitals in Brazil. DESIGN AND METHODS: In this cross
      sectional study, emotional and behavioral symptoms were assessed using the
      Children Behavior Checklist (CBCL) in three groups of children aged 5-14 years:
      a) children with acute leukemia (n = 21); b) children with blood dyscrasias (n =
      21); c) children evaluated or treated in a pediatric outpatient service (n = 33).
      RESULTS: Children with blood dyscrasias had significantly few symptoms of
      externalization (delinquent and aggressive behavior) than pediatric controls (p<
      0.05). Children with leukemia did not differ from the two other groups regarding
      symptoms of externalization. No significant difference on the scores of the CBCL
      internalization dimension (anxiety, depression, somatic symptoms and withdrawn)
      was found among the three groups. INTERPRETATION AND CONCLUSIONS: These findings
      seem to indicate that children with acute leukemia do not have more emotional or
      behavioral symptoms than children with benign hematologic or physical diseases
      suggesting that comorbidity with mental disorders is not higher in children with
      acute leukemia than in children in the other two groups.

PMID- 11522539
TI  - Clinical tumor cell distribution pattern is a prognostically relevant parameter
      in patients with B-cell chronic lymphocytic leukemia.
AB  - BACKGROUND AND OBJECTIVES: B-cell chronic lymphocytic leukemia (B-CLL) cells are
      variably distributed among the major lymphoid compartments contributing to the
      heterogeneous clinical presentation and course of this disease. In order to
      evaluate this variable distribution we propose a model for its clinical
      assessment. DESIGN AND METHODS: We introduce the model for tumor distribution
      (TD) assessment based on TTM scoring system, where TD value represents percentage
      of total tumor mass infiltrating peripheral blood and bone marrow (TD=TM(1)/TTM).
      TD in B-CLL can be categorized into 3 subgroups: pure leukemia if TD=100%,
      predominantly leukemia if TD=50-99% and predominantly lymphoma TD<50%. RESULTS:
      Among 341 B-CLL patients there were 22.6%, 55.1%, 22.3%, pure leukemia,
      predominantly leukemia and predominantly lymphoma cases, respectively. TD
      parameter was strongly associated in univariate analysis with TTM size, Rai and
      Binet stages, spleen size and beta(2) microglobulin. TD was associated with
      response to therapy and survival, with higher TD values translated into higher
      response rates and longer survival. However, in univariate and multivariate Cox
      analysis TD displayed much stronger relationship with prognosis in female
      patients, where it is the strongest independent predictor of survival along with
      age and Binet stage. INTERPRETATION AND CONCLUSIONS: TD, a quantitative and
      simple clinical parameter, easily assessed in all patients, offers a reliable
      tool for evaluation of tumor cell distribution in B-CLL. It has independent and
      strong prognostic power in females, as opposed to males, possibly unmasking
      important, yet unrecognized, biological difference in B-CLL patients.

PMID- 11522540
TI  - Differentiation of monoclonal gammopathy of undetermined significance and
      multiple myeloma using flow cytometric characteristics of plasma cells.
AB  - BACKGROUND AND OBJECTIVES: The differential diagnosis between multiple myeloma
      (MM) and monoclonal gammopathy of undetermined significance (MGUS) may be
      uncertain in some cases; this problem is reflected by discrepancies between
      different classification systems with an accordance in only 2/3 of cases. We
      studied whether flow-cytometric characteristics of plasma cells (PC) can be used
      for the differentiation between MGUS and MM. DESIGN AND METHODS: Patients were
      divided into 3 groups: Group A included 13 myeloma patients with a plasma cell
      infiltration of the bone marrow of 10-30%, serum M-protein < or = 3.5 g/dL (IgG)
      or < or = 2 g/dl (IgA) and without bone lesions in conventional radiography.
      Group B consisted of 53 patients who fulfilled the Durie and Salmon diagnostic
      criteria including at least one major criterion, and group C individuals with
      MGUS (n=17). The ratio of immunophenotypically normal (i.e. CD19(+)/CD56(-)) to
      all bone marrow plasma cells (BMPC), the number of peripheral blood PC (PBPC),
      the percentage of BMPC in S-phase and the DNA content of BMPC were analyzed.
      RESULTS: All individuals with MGUS and no patient with MM in group A or group B
      had a ratio of phenotypically normal to all BMPC > or = 20%. The median of
      monoclonal PBPC was 0/microL (range 0-2/ microL) in MGUS, 1/microL (range 0
      30/microL) in MM group A and 2.4/microL (range 0-211/microL) in MM group B. The
      median percentage of BMPC in S-phase was 1.6% both in MGUS and in group A and 3%
      in group B. Aneuploidy was found in 12%, 11% and 41% in MGUS, group A and group
      B, respectively. INTERPRETATION AND CONCLUSIONS: The ratio of
      immunophenotypically normal to all BMPC was the only flow-cytometric parameter
      for the differentiation of MGUS and MM group A (p<0.0005). The other parameters
      were significantly different between MGUS and MM group B, but not group A.

PMID- 11522541
TI  - Frequently relapsing thrombotic thrombocytopenic purpura treated with cytotoxic
      immunosuppressive therapy.
AB  - BACKGROUND AND OBJECTIVES: Treatment of thrombotic thrombocytopenic purpura (TTP)
      with plasma exchange has reduced mortality rates from 90% in untreated cases to
      less than 20%. Despite plasma exchange, relapses may occur in as many as 40% of
      cases. Multiple relapses occur in a minority but pose a significant therapeutic
      challenge. Recent evidence supports the presence of an autoantibody which
      inhibits proteolysis of von Willebrand factor (vWF) in active TTP, allowing large
      multimers of vWF to form and promote platelet aggregation. Additional evidence
      suggests autoantibodies activate capillary endothelium and promote platelet
      aggregation in the microcirculation. Immunosuppression, thus, has a biologically
      plausible role in TTP. We describe three consecutive cases of relapsing TTP
      treated with cytotoxic therapy to highlight the potential role of
      immunosuppression. DESIGN AND METHODS: Cytotoxic immunosuppressive therapy with
      either cyclophosphamide or azathioprine was used in three consecutive patients
      with frequently relapsing TTP. RESULTS: All three patients have maintained
      remissions of 8 to 10 months without recurrence. INTERPRETATION AND CONCLUSIONS:
      Cytotoxic immunosuppressive therapy may have a role in inducing long-term
      remissions in recurrent TTP.

PMID- 11522542
TI  - Use of EDTA samples for prothrombin time measurement in patients receiving oral
      anticoagulants.
AB  - BACKGROUND AND OBJECTIVES: Oral anticoagulant therapy is commonly called for in
      health care. Hitherto sampling for prothrombin time (PT) has been measured on
      blood collected into a coagulation tube and diluted in citrate solution. Blood
      samples anticoagulated with EDTA are used for hematologic tests and the same
      sample could also be available for PT. DESIGN AND METHODS: We studied 107
      patients on oral anticoagulant therapy. Samples were taken by from both
      coagulation tubes (citrate) and EDTA tubes. The PT from both samples was measured
      with an ACL 7000 analyzer and reported in seconds and as an international
      normalized ratio (INR). The regression equation between citrate and EDTA samples
      was calculated in both units. We studied the clinical significance of INR results
      from both sample types and compared the effect of different combined
      thromboplastin reagents on the correlation equation between citrate and EDTA
      samples. RESULTS: The regression equation for PT by Owren's PT reagent from
      citrate (y) and EDTA (x) plasma was y = 1.11 x -0.24 INR, R(2)= 0.99. We observed
      no clinically significant difference between INR results from citrate and EDTA
      samples using the regression equation for INR calculation from EDTA samples. ISI
      depends on sample type (dilution, anticoagulant) and the difference is 0.117,
      10%. We calculated ISI for EDTA samples and no clinically significant difference
      was seen between citrate and EDTA INR results. INTERPRETATION AND CONCLUSIONS: A
      good correlation was observed between INR results with citrate and EDTA samples
      from patients receiving oral anticoagulants using Owren's PT reagent with the
      same citrate calibration. Using the regression equation (INR or sec) for analysis
      of INR results from EDTA samples is clinically acceptable and offers the
      possibility of using EDTA samples for PT measurement with citrate calibrators.
      Reagent international sensitivity index (ISI) values for citrate and EDTA samples
      differ from each other. ISI determination for EDTA samples requires mathematical
      calculation of EDTA ISI as in the present study or EDTA-based ISI calibrators.
      The regression equation for INR from citrate and EDTA samples depended on the
      reagent used, not only on sample dilution or anticoagulant.

PMID- 11522543
TI  - A rapid D-dimer assay in patients presenting at the emergency room with suspected
      acute venous thrombosis: accuracy and relation to clinical variables.
AB  - BACKGROUND AND OBJECTIVES: The measurement of D-dimer is claimed to have
      potential value in excluding deep vein thrombosis (DVT). New rapid methods have
      been proposed, but few clinical trials have assessed their performance in an
      emergency context. The different accuracies found between the D-dimer assays have
      been related to the test used (latex or ELISA), but other variables (such as
      population investigated, thrombus extension, duration of symptoms or concomitant
      heparin treatment) may be important, even if not sufficiently investigated.
      DESIGN AND METHODS: We evaluated the accuracy of a rapid semi-quantitative D
      dimer test (Dimertest, Dade Behring), with reference to: a) its use at an
      emergency unit; b) concomitant heparin administration; c) location of venous
      thrombosis (VT) (in the deep or superficial venous system limited to the great
      saphenous vein) and d) symptoms older than 14 days. RESULTS: Two hundred and
      ninety-eight patients suspected of having DVT and 116 suspected of thrombosis of
      the great saphenous vein (GSV) were investigated. In the DVT patients, the
      sensitivity, specificity, positive and negative predictive values were 77.4% (95%
      CI 68.9-85.9), 81.4% (95% CI 76.1-86.7), 65.4% (95% CI 56.5-74.3) and 88.8% (95%
      CI 84.2-93.4), respectively. Excluding patients receiving heparin and those with
      symptoms older than 15 days, the sensitivity and negative predictive value
      increased to 86.3% (95% CI 78.4-94.2) and 92.8% (95% CI 88.4-97.2), respectively.
      In patients with GSV thrombosis, the sensitivity, specificity, positive and
      negative predictive values were 48% (95% CI 34.5-61.5), 90.6% (95% CI 83.2-97.9),
      80.6% (95% CI 66.6-94.6) and 68.2% (95% CI 57.8-78.6), respectively. Excluding
      patients receiving heparin and those with symptoms older than 15 days, did not
      change the sensitivity or negative predictive value significantly. INTERPRETATION
      AND CONCLUSIONS: Our results show that previous or concomitant heparin
      administration, non-acute symptoms and thrombosis localized to superficial veins
      reduce the clinical usefulness of the D-dimer test as the rate of false negative
      results is increased.

PMID- 11522544
TI  - Infections caused by filamentous fungi in patients with hematologic malignancies.
      A report of 391 cases by GIMEMA Infection Program.
AB  - BACKGROUND AND OBJECTIVES: To evaluate the clinical characteristics of patients
      with hematologic malignancies developing a filamentous fungi infection (FFI) and
      to define the prognostic factors for their outcome. DESIGN AND METHODS: A
      retrospective study, conducted on patients admitted to 14 Hematology divisions of
      tertiary care or university hospitals, participating in the GIMEMA Infection
      Program, over a ten-year period (1988-1997). The study included patients with
      hematological malignancies and a histologically and/or microbiologically proven
      or probable FFI. RESULTS: We included 391 patients (male/female: 262/129, median
      age 49 years) with hematologic malignancies (225 acute myeloid leukemia, 67 acute
      lymphocytic leukemia, 30 chronic myeloid leukemia, 22 non-Hodgkin's lymphoma, 12
      myelodysplastic syndrome, 10 aplastic anemia, 7 Hodgkin's disease, 8 chronic
      lymphocytic leukemia, 5 multiple myeloma, and 5 hairy cell leukemia) who
      developed a proven FFI. Eighty percent of the patients had been neutropenic for
      an average of 14 days before the infection, and 71% had an absolute neutrophil
      count lower than 0.5 x 10(9)/L at the time of FFI diagnosis. The primary sites of
      infection were: lungs (85%), nose and paranasal sinus (10%), and other sites
      (5%). The diagnosis was made while still alive in 310 patients (79%), and at
      autopsy in the remaining 81 patients (21%). Chest X-ray was diagnostic in 77% of
      patients with pulmonary FFI, while computed tomography (CT) scan of the thorax
      was positive in 95% of cases. A significant diagnostic advantage for CT scan was
      observed in 145 patients who had both a chest X-ray and CT scan. Aspergillus was
      identified as the cause of FFI in 296 patients, Mucorales in 45 patients,
      Fusarium in 6 patients and other filamentous fungi species in 4 patients, while
      in a further 40 patients no agent was identifiable. The overall mortality rate
      three months after the diagnosis of FFI was 74%, and fungal infection had been
      the cause of death in 51% of patients. INTERPRETATION AND CONCLUSIONS: Our
      retrospective study shows that FFI still remains a life-threatening complication
      in neutropenic patients. Despite appropriate treatment, half of the patients die
      due to this complication. The use of glucocorticoids and recovery from
      neutropenia are the most important prognostic factors. Mucorales infections are
      associated with a significantly poorer prognosis than those due to Aspergillus
      spp.

PMID- 11522545
TI  - Recurrent A353V mutation in a Thai family with X-linked dyskeratosis congenita.

PMID- 11522546
TI  - Leptin concentrations in US adults.

PMID- 11522547
TI  - Diet, alcohol, and health: a story of connections, confounders, and cofactors.

PMID- 11522548
TI  - Statistical and psychobiological significance in developmental research.

PMID- 11522549
TI  - Individual metabolism should guide agriculture toward foods for improved health
      and nutrition.
AB  - Genomics and bioinformatics have the vast potential to identify genes that cause
      disease by investigating whole-genome databases. Comparison of an individual's
      geno-type with a genomic database will allow the prescription of drugs to be
      tailored to an individual's genotype. This same bioinformatic approach, applied
      to the study of human metabolites, has the potential to identify and validate
      targets to improve personalized nutritional health and thus serve to define the
      added value for the next generation of foods and crops. Advances in high
      throughput analytic chemistry and computing technologies make the creation of a
      vast database of metabolites possible for several subsets of metabolites,
      including lipids and organic acids. In creating integrative databases of
      metabolites for bioinformatic investigation, the current concept of measuring
      single biomarkers must be expanded to 3 dimensions to 1) include a highly
      comprehensive set of metabolite measurements (a profile) by multiparallel
      analyses, 2) measure the metabolic profile of individuals over time rather than
      simply in the fasted state, and 3) integrate these metabolic profiles with
      genomic, expression, and proteomic databases. Application of the knowledge of
      individual metabolism will revolutionize the ability of nutrition to deliver
      health benefits through food in the same way that knowledge of genomics will
      revolutionize individual treatment of dis-ease with pharmaceuticals.

PMID- 11522550
TI  - Family social class, maternal body mass index, childhood body mass index, and age
      at menarche as predictors of adult obesity.
AB  - BACKGROUND: Obesity is an increasingly prevalent nutritional disorder throughout
      the world and is a risk factor for many chronic diseases. The prevalence of
      obesity increases with age. OBJECTIVE: The objective was to evaluate the
      associations between BMI at 31 y of age and family social class during early
      childhood, maternal body mass index (BMI) before pregnancy, BMI at birth and at 1
      and 14 y of age, and age at menarche. DESIGN: This was a longitudinal study of
      the northern Finland birth cohort for 1966. Subjects were measured at birth and
      at 1, 14, and 31 y of age. The analysis was restricted to individuals for whom
      BMI data were available for all measurement points (n = 2876 males and 3404
      females). RESULTS: The mean BMI at birth was highest in offspring from the
      highest social classes, but BMI was inversely related to social class at 1 y.
      BMI, the waist-to-hip ratio, and the proportion of obese subjects were inversely
      related to social class at 31 y. The heavier the mother, the heavier the
      offspring from birth to 31 y. The paired analyses between maternal BMI and
      daughter's BMI at 31 y showed no significant difference in BMI after adjustment
      for the age difference. BMI at 14 y was the most important predictor of BMI at 31
      y. Early menarche in females was associated with a higher BMI at 14 and 31 y.
      CONCLUSIONS: Differences in BMI by social class are formed at least partly during
      early childhood. Low social class of the child's family, a high maternal BMI
      before pregnancy, a high BMI during adolescence, and early menarche are
      predictors of obesity in adulthood.

PMID- 11522551
TI  - Leptin concentrations in the United States: relations with demographic and
      anthropometric measures.
AB  - BACKGROUND: Leptin is a peptide that is strongly correlated with adiposity and is
      a potential determinant of obesity and its complications. OBJECTIVE: Leptin
      concentrations from a representative sample of the US population were examined in
      relation to demographic and anthropometric measures. DESIGN: Fasting serum leptin
      concentrations were measured in 6303 women and men aged > or =20 y in the third
      National Health and Nutrition Examination Survey. Anthropometric measures
      included body mass index, 4 skinfold thicknesses, and 4 body circumferences.
      Ethnic groups included non-Hispanic whites and blacks and Mexican Americans.
      RESULTS: The mean serum leptin concentration was much higher in women (12.7
      microg/L) than in men (4.6 microg/L). In a multivariate analysis, leptin
      concentrations were associated with the sum of 4 skinfold thicknesses, waist and
      hip circumferences, ethnicity, and age. These measures explained most of the
      variance in leptin concentrations in women (R2 = 0.69) and in men (R2 = 0.67).
      Triceps skinfold thickness, when substituted for the sum of skinfold thicknesses,
      performed nearly as well in women (R2 = 0.68) and men (R2 = 0.67). Leptin
      concentrations were slightly but significantly higher in non-Hispanic blacks than
      in non-Hispanic whites of both sexes when these anthropometric measures and age
      were controlled for; Mexican Americans had concentrations that were intermediate
      compared with the concentrations of non-Hispanic whites and blacks. CONCLUSIONS:
      In this large, representative sample of the US population, demographic and
      anthropometric measures predicted serum leptin concentrations in women and men.

PMID- 11522552
TI  - Abstention from filtered coffee reduces the concentrations of plasma homocysteine
      and serum cholesterol--a randomized controlled trial.
AB  - BACKGROUND: Elevated concentrations of plasma total homocysteine (tHcy) and serum
      total cholesterol are risk factors for ischemic heart disease (IHD). Previous
      studies showed that the consumption of very high doses of unfiltered coffee
      increases tHcy and total cholesterol. OBJECTIVE: A prospective intervention study
      was performed to assess the effects of coffee consumption on the concentrations
      of tHcy and total cholesterol by using doses and brewing methods common in
      southeastern Norway. DESIGN: The study was an unblinded, controlled trial with
      191 healthy, nonsmoking, coffee-drinking volunteers aged 24-69 y randomly
      assigned to 3 groups who were asked to consume for 6 consecutive weeks no coffee,
      1-3 cups (approximately 175-525 mL)/d, or > or =4 cups (approximately 700 mL)/d
      prepared in the manner to which they were accustomed. Blood samples were drawn
      when the subjects were randomly assigned and at 3 and 6 wk of the trial. Dietary
      data were collected by questionnaire. RESULTS: Ninety-seven percent of the
      participants reported being regular consumers of caffeinated filtered coffee.
      Abstention from coffee for 6 wk was associated with a decrease in the tHcy
      concentration of 1.08 micromol/L and a decrease in the total cholesterol
      concentration of 0.28 mmol/L in participants who had been drinking on average 4
      cups of filtered coffee daily for the past year. Adjustments for several possible
      confounders did not alter the results. CONCLUSION: Abstention from filtered
      coffee in doses that are commonly consumed was associated with lower
      concentrations of tHcy and total cholesterol.

PMID- 11522553
TI  - Effects of a National Cholesterol Education Program Step II Diet on
      apolipoprotein A-IV metabolism within triacylglycerol-rich lipoproteins and
      plasma.
AB  - BACKGROUND: Apolipoprotein (apo) A-IV is a major component of triacylglycerol
      rich lipoprotein (TRL) apolipoproteins. OBJECTIVE: We investigated the effects of
      dietary saturated fat and cholesterol restriction on the metabolism of TRL and
      plasma apo A-IV. DESIGN: We assessed TRL and plasma apo A-IV kinetics in 16 and 4
      subjects, respectively, consuming an average US (baseline) diet for 6 wk and a
      National Cholesterol Education Program Step II diet for 24 wk, respectively. At
      the end of each diet period, all subjects received a primed, constant infusion of
      deuterated leucine for 15 h with hourly feeding. Ratios of stable-isotope tracer
      to tracee were measured by using gas chromatography-mass spectrometry, and
      kinetic data were modeled by using SAAM II. RESULTS: Mean apo A-IV concentrations
      during the isotope infusion period were 6.9 +/- 2.6 mg/L in TRL and 2.2 +/- 3.2
      mg/L in plasma with the baseline diet; these values were 37.7% (P < 0.001) and
      19.4% (P < 0.01) lower with the Step II diet. Similar changes were observed in
      the fasting state between the 2 diets. The mean apo A-IV secretion rate decreased
      significantly from baseline by 59.6% in TRLs and by 40.2% in plasma. Significant
      correlations were observed between TRL apo A-IV concentrations and the secretion
      rate (r = 0.94, P < 0.001) and between TRL apo A-IV pool size and TRL-cholesterol
      concentrations (r = 0.48, P < 0.01). CONCLUSIONS: Our data indicate that the
      National Cholesterol Education Program Step II diet significantly decreases TRL
      and plasma apo A-IV concentrations compared with the average US diet and that
      this decrease is due to a decreased secretion rate.

PMID- 11522554
TI  - Waist and hip circumferences have independent and opposite effects on
      cardiovascular disease risk factors: the Quebec Family Study.
AB  - BACKGROUND: A high waist-to-hip ratio is associated with unfavorable
      cardiovascular disease risk factors. This could be due to either a relatively
      large waist or a small hip girth. OBJECTIVE: We sought to define the separate
      contributions of waist girth, hip girth, and body mass index (BMI) to measures of
      body composition, fat distribution, and cardiovascular disease risk factors.
      DESIGN: Three-hundred thirteen men and 382 women living in the greater Quebec
      City area were involved in this cross-sectional study. Percentage body fat,
      anthropometric measurements, and abdominal fat distribution were obtained and BMI
      (in kg/m2) and waist-to-hip ratio were calculated. Serum blood lipids were
      determined from blood samples collected after subjects had fasted overnight
      RESULTS: A large waist circumference in men and women (adjusted for age, BMI, and
      hip circumference) was associated significantly with low HDL-cholesterol
      concentrations (P < 0.05) and high fasting triacylglycerol, insulin, and glucose
      concentrations (P < 0.01). In women alone, a large waist circumference was also
      associated with high LDL-cholesterol concentrations and blood pressure. A narrow
      hip circumference (adjusted for age, BMI, and waist circumference) was associated
      with low HDL-cholesterol and high glucose concentrations in men (P < 0.05) and
      high triacylglycerol and insulin concentrations in men and women (P < 0.05).
      Waist and hip girths showed different relations to body fat, fat-free mass, and
      visceral fat accumulation. CONCLUSIONS: Waist and hip circumferences measure
      different aspects of body composition and fat distribution and have independent
      and often opposite effects on cardiovascular disease risk factors. A narrow waist
      and large hips may both protect against cardiovascular disease. These specific
      effects of each girth measure are poorly captured in the waist-to-hip ratio.

PMID- 11522555
TI  - Do eating habits differ according to alcohol consumption? Results of a study of
      the French cohort of the European Prospective Investigation into Cancer and
      Nutrition (E3N-EPIC).
AB  - BACKGROUND: The potential of dietary habits to confound the association between
      alcohol consumption and health needs further study. OBJECTIVE: We examined
      whether eating habits differed according to alcohol consumption in a large cohort
      of French women. DESIGN: This was a cross-sectional study of the French cohort of
      the European Prospective Investigation into Cancer and Nutrition (E3N-EPIC). The
      cohort was established in 1990 and includes 100000 women born between 1925 and
      1950. Dietary data were obtained between 1993 and 1995 by using self-administered
      food-frequency questionnaires. About 73000 questionnaires were analyzed, and
      women were placed into 7 categories of alcohol consumption. RESULTS: After
      adjustment for energy derived from alcohol, increasing alcohol consumption was
      associated with a higher total energy intake, a higher percentage of energy
      intake as protein and lipids, and higher intakes of cholesterol, fatty acids,
      retinol, iron, and vitamin E. Conversely, energy provided by carbohydrates
      decreased with increasing alcohol consumption, as did beta-carotene intake.
      Increasing alcohol consumption was associated with higher consumption of animal
      products, cheese, potatoes, oil, bread, and breakfast cereals and with lower
      consumption of vegetables and dairy products. CONCLUSION: In this population of
      middle-aged, highly educated French women, marked differences in dietary patterns
      and nutrient intakes were found according to alcohol consumption. Part of the
      detrimental effect of alcohol on health may be due to the less healthy dietary
      habits of drinkers. This points to a confounding role of eating habits and
      nutrient intakes in the relation between alcohol and health.

PMID- 11522556
TI  - Factors correlated with hypermetabolism in patients with amyotrophic lateral
      sclerosis.
AB  - BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a severe disease characterized
      by neurogenic amyotrophy and degeneration of upper and lower motor neurons.
      Although ALS patients usually experience reductions in fat-free mass (FFM),
      hypermetabolism via an undetermined source has also been reported. OBJECTIVE: The
      objective was to clarify the metabolic level of ALS patients. DESIGN: We measured
      the resting energy expenditure (REE) of 62 patients (32 men and 30 women) with
      ALS and investigated the factors correlated with metabolic level. Nutritional
      evaluation included bioelectrical impedance analysis, indirect calorimetry, and
      calculation of the body mass index. Neurologic assessment included an evaluation
      of peripheral and central neurologic deficit. Forced vital capacity was measured
      and smoking status was noted. A complete blood cell count was made and thyroid
      hormone and C-reactive protein concentrations were measured. RESULTS: Patients
      were hypermetabolic, by an average of approximately 10% more than in a reference
      healthy population. FFM, age, and the neutrophil count were significantly
      associated with REE. The only variable that contributed to the prediction of REE,
      REE/Z100 kHz (bioimpedance at 100 kHz), REE adjusted for FFM, or the ratio of
      measured REE to calculated REE was the neutrophil count, which explained only a
      small percentage of variance in the multiple regression analysis. Hypermetabolism
      was not associated with a reduction in respiratory function, tobacco use,
      hyperthyroidism, spasticity and fasciculation intensities, or infection.
      CONCLUSIONS: Our study corroborates the surprising finding that ALS patients are
      hypermetabolic. FFM, age, sex, manual muscular testing, the modified Norris limb
      score, weight, and an increase in circulating neutrophil counts correlated with
      the hypermetabolic state. Other factors may play a role in pathophysiologic
      processes that involve mitochondrial energy production or even sympathoadrenergic
      activation.

PMID- 11522557
TI  - Does it make a difference how and when you take your calcium? The acute effects
      of calcium on calcium and bone metabolism.
AB  - BACKGROUND: Calcium supplements are widely used to prevent osteoporosis. However,
      little is known about the metabolic effects of different dosages and of the
      timing of the dosages. OBJECTIVE: The aim was to study the effects of the timing
      of the dose (study 1), the effects of the size of the dose (study 2), and the
      effects of small repetitive doses (study 3) of calcium on calcium and bone
      metabolism in women. DESIGN: The investigation was conducted in 3 parts, each
      with 10 participants. In study 1, calcium loads (0 and 25 mg/kg body wt) were
      taken at 0900 and 2100. In study 2, calcium loads of 0, 250, and 1000 mg were
      taken at 0900. In study 3, calcium loads of 0 and 200 mg were taken 4 times/d.
      Markers of calcium and bone metabolism were followed. RESULTS: There was no
      significant difference in the response of serum parathyroid hormone (PTH) to the
      calcium load taken at 0900 and that at 2100. There was a significant dose
      response effect of the calcium load on serum ionized calcium (P = 0.00005) and
      serum PTH (P = 0.0003). Small calcium doses (200 mg) taken 4 times/d kept the PTH
      secretion at a lower level than during the control day (P = 0.016). None of the
      doses caused significant changes in the markers of bone formation and resorption
      measured. CONCLUSIONS: The calcium loads had no significant effect on the markers
      of bone formation and resorption measured, although even small calcium doses
      decreased serum PTH and increased serum ionized calcium concentrations rapidly.
      The effect was similar whether calcium was taken in the morning or in the
      evening.

PMID- 11522558
TI  - Carbonated beverages and urinary calcium excretion.
AB  - BACKGROUND: Intake of carbonated beverages has been associated with increased
      fracture risk in observational studies. The usual explanation given is that one
      or more of the beverage constituents increase urinary calcium. OBJECTIVE: We
      assessed the short-term effects on urinary calcium excretion of carbonated
      beverages of various compositions. DESIGN: An incomplete random block design was
      used to study 20-40-y-old women who customarily consumed > or =680 mL carbonated
      beverages daily. Four carbonated beverages were tested: 2 with caffeine and 2
      without. Two contained phosphoric acid as the acidulant and 2 contained citric
      acid. The study included one neutral control (water) and one positive control
      (skim or chocolate milk). Serving size was 567 mL for the carbonated beverages
      and water and 340 mL for the milks. Beverages were consumed with a light
      breakfast after an overnight fast; no other foods were ingested until urine
      collection was complete. pH, titratable and total acidity, sodium, creatinine,
      and calcium were measured in 2-h (morning) fasting and 5-h postbeverage urine
      specimens. RESULTS: Relative to water, urinary calcium rose significantly only
      with the milks and the 2 caffeine-containing beverages. The excess calciuria was
      approximately 0.25 mmol, about the same as previously reported for caffeine
      alone. Phosphoric acid without caffeine produced no excess calciuria; nor did it
      augment the calciuria of caffeine. CONCLUSIONS: The excess calciuria associated
      with consumption of carbonated beverages is confined to caffeinated beverages.
      Acidulant type has no acute effect. Because the caffeine effect is known to be
      compensated for by reduced calciuria later in the day, we conclude that the net
      effect of carbonated beverage constituents on calcium economy is negligible. The
      skeletal effects of carbonated beverage consumption are likely due primarily to
      milk displacement.

PMID- 11522559
TI  - A novel extrinsic reference method for assessing the vitamin A value of plant
      foods.
AB  - BACKGROUND: The amounts of vitamin A that are metabolically derived from specific
      carotene-containing foods are largely unknown. OBJECTIVE: We sought to develop an
      improved method for estimating the metabolic vitamin A potential of provitamin A
      carotenoids by using [2H4]retinyl acetate (d4-RA) as an extrinsic reference
      standard. DESIGN: Healthy subjects consumed a standardized test meal containing 6
      mg beta-carotene as either raw carrot or spinach, either 20 or 1 g added fat, and
      6.0 micromol d4-RA. Concentrations of unlabeled (d0) retinyl esters (RE), labeled
      (d4) RE, and carotenoids in the plasma triacylglycerol-rich lipoprotein fraction
      (d < 1.006 kg/L) were determined in serial blood samples with HPLC and gas
      chromatography-mass spectrometry. Baseline-corrected areas under the curve for d0
      RE, d4-RE, and carotenoids were calculated, and the masses of absorbed d0-retinol
      and carotenes were estimated assuming 80% absorption of the d4-RA reference dose.
      RESULTS: In trials with ample (20 g) fat (n = 6), 7 +/- 4% of the 6 mg beta
      carotene ingested was taken up as beta-carotene plus RE with 0.3 +/- 0.1 mg as
      retinol. Test meals without carotenes yielded no beta-carotene or d0-RE response
      and there was no effect of treatment (either fat amount or vegetable, n = 6) on
      the mean d4-RE area under the curve. The lower-than-expected vitamin A yields
      were attributed to poor intestinal uptake rather than to low conversion of beta
      carotene to RE. CONCLUSION: The triacylglycerol-rich lipoprotein and d4-RA
      method, which controls for variation in chylomicron kinetics in vivo and RE
      recovery during analysis, is useful for obtaining quantitative estimates of the
      vitamin A potential of single meals.

PMID- 11522560
TI  - Population-based study of alpha- and gamma-tocopherol in plasma and adipose
      tissue as biomarkers of intake in Costa Rican adults.
AB  - BACKGROUND: gamma-Tocopherol is the most abundant form of vitamin E in the US
      diet, but alpha-tocopherol concentrations are the highest in plasma and tissues.
      Although plasma and adipose tissue concentrations of alpha-tocopherol have been
      used as biomarkers of intake, the relation between gamma-tocopherol intake and
      concentrations in plasma and adipose tissue is unknown. OBJECTIVE: Our goal was
      to investigate in a randomly selected population from Costa Rica whether plasma
      or adipose tissue concentrations of alpha- and gamma-tocopherol are suitable
      biomarkers of intake. DESIGN: A total of 361 men (x +/- SD age: 55 +/- 11 y) and
      121 women (aged 59 +/- 10 y) completed a 135-item food-frequency questionnaire
      and provided a fasting blood sample and adipose tissue biopsy sample. RESULTS:
      Dietary gamma-tocopherol correlated with adipose tissue (r = 0.37, P < 0.001) and
      plasma (r = 0.42, P < 0.001) concentrations, regardless of supplement use.
      Dietary alpha-tocopherol correlated poorly with adipose tissue (r = 0.15, P <
      0.01) and plasma (r = 0.16, P < 0.001) concentrations, and these correlations
      were even lower when users of vitamin supplements (n = 24) were excluded (adipose
      tissue: r = 0.10, P < 0.05; plasma: r = 0.09, P < 0.05). Compared with subjects
      who reported palm shortening (36%) as the major type of fat used for cooking,
      subjects using soybean oil (52%) had higher amounts of both alpha- and gamma
      tocopherol in their diets. However, only gamma-tocopherol concentrations were
      higher in the plasma and adipose tissue of soybean oil users. CONCLUSIONS: Plasma
      and adipose tissue concentrations of gamma-tocopherol are equally good biomarkers
      of intake. The weak associations between alpha-tocopherol intake and plasma or
      adipose tissue concentrations suggest that these biomarkers are influenced more
      by factors other than alpha-tocopherol intake.

PMID- 11522562
TI  - Resting metabolic rate in obese and nonobese Chinese Singaporean boys aged 13-15
      y.
AB  - BACKGROUND: Previous studies investigating the hypothesis that a low resting
      metabolic rate (RMR) is a cause of obesity yielded discrepant findings. Two
      explanations for these findings are the use of imprecise methods to determine
      obesity and a failure to control for differences in fat mass (FM) and fat-free
      mass (FFM) when comparing RMR values. OBJECTIVE: This study tested the hypothesis
      that RMR is lower in obese than in nonobese boys (with the use of precise methods
      to quantify body fatness and with adjustment for differences in both FM and FFM).
      DESIGN: Forty Chinese Singaporean boys aged 12.8-15.1 y were recruited. Boys were
      classified as obese (n = 20) or nonobese (n = 20) on the basis of their adiposity
      index (ratio of FM to FFM: >0.60 = obese, <0.40 = nonobese) determined by dual
      energy X-ray absorptiometry. RMR was determined by using indirect calorimetry.
      RMR values were compared by using both linear (analysis of covariance) and log
      linear (analysis of covariance with log-transformed data) regression to control
      for differences in FM and FFM. RESULTS: Age, height, and FFM did not differ
      significantly between groups. Body mass was 13 kg greater and FM was 16 kg
      greater in the obese boys than in the nonobese boys (P < 0.001). After control
      for FFM and FM, RMR did not differ significantly between the groups. CONCLUSION:
      When body composition is appropriately controlled for, RMR does not differ
      significantly between obese and nonobese boys.

PMID- 11522561
TI  - Inverse association between trans isomeric and long-chain polyunsaturated fatty
      acids in cord blood lipids of full-term infants.
AB  - BACKGROUND: Previous studies showed significant inverse correlations between
      values of trans isomeric and long-chain polyunsaturated fatty acids in plasma
      lipids of preterm infants and healthy children aged 1-15 y. OBJECTIVE: We sought
      to evaluate the same correlations in full-term infants at birth. DESIGN: We
      studied healthy full-term infants (n = 42) born after normal pregnancies and
      deliveries. All infants had a family history of atopy (both parents or one of the
      parents and a sibling had atopic symptoms). The fatty acid composition of venous
      cord blood lipids was determined by high-resolution capillary gas-liquid
      chromatography. RESULTS: The mean (+/-SEM) sum of trans fatty acids was 0.49 +/-
      0.02% by wt in phospholipids, 2.47 +/- 0.20% by wt in cholesterol esters, 1.73 +/
      0.09% by wt in triacylglycerols, and 1.59 +/- 0.07% by wt in nonesterified fatty
      acids. Linear correlation analysis showed significant inverse correlations
      between the sum of trans fatty acids and both arachidonic acid and
      docosahexaenoic acid in phospholipids (r = -0.56, P < 0.001, and r = -0.48, P =
      0.01, respectively), cholesterol esters (r = -0.52, P < 0.001, and r = -0.39, P =
      0.018, respectively), and nonesterified fatty acids (r = -0.41, P = 0.007, and r
      = -0.41, P = 0.006, respectively). CONCLUSION: Because trans fatty acids in the
      fetal circulation must originate from the maternal diet, our results indicate
      that maternal exposure to trans fatty acids may represent a previously neglected
      variable that inversely influences long-chain polyunsaturated fatty acid status
      in full-term infants at birth.

PMID- 11522563
TI  - Effects of quality of energy on substrate oxidation in enterally fed, low-birth
      weight infants.
AB  - BACKGROUND: Carbohydrate and fat may differ in their ability to support energy
      requiring physiologic processes, such as protein synthesis and growth. If so,
      varying the constituents of infant formula might be therapeutically advantageous.
      OBJECTIVE: We tested the hypothesis that low-birth-weight infants fed a diet
      containing 65% of nonprotein energy as carbohydrate oxidize relatively more
      carbohydrate and relatively less protein than do infants fed an isoenergetic,
      isonitrogenous diet containing 35% of nonprotein energy as carbohydrate. DESIGN:
      Sixty-two low-birth-weight infants weighing from 750 to 1600 g at birth were
      assigned randomly and blindly to receive 1 of 5 formulas that differed only in
      the quantity and quality of nonprotein energy. Formula containing 544 kJ x kg(-1)
      x d(-1) with either 50%, 35%, or 65% of nonprotein energy as carbohydrate was
      administered to control subjects, group 1, and group 2, respectively. Groups 3
      and 4 received gross energy intakes of 648 kJ x kg(-1) x d(-1) with 35% and 65%
      of nonprotein energy as carbohydrate. Protein intake was targeted at 4 g x kg(-1)
      x d(-1). Substrate oxidation was estimated from biweekly, 6-h measurements of gas
      exchange and 24-h urinary nitrogen excretion. RESULTS: Carbohydrate oxidation was
      positively (r = 0.71, P < 0.0001) and fat oxidation was negatively (r = -0.46, P
      < 0.001) correlated with carbohydrate intake. Protein oxidation was negatively
      correlated with carbohydrate oxidation (r = -0.42, P < 0.001). Fat oxidation was
      not correlated with protein oxidation. Protein oxidation was less in infants
      receiving 65% of nonprotein energy as carbohydrate than in groups receiving 35%
      nonprotein energy as carbohydrate. CONCLUSION: These data support the hypothesis
      that energy supplied as carbohydrate is more effective than energy supplied as
      fat in sparing protein oxidation in enterally fed low-birth-weight infants.

PMID- 11522564
TI  - Randomized controlled trial of the effect of zinc supplementation on the mental
      development of Bangladeshi infants.
AB  - BACKGROUND: Zinc deficiency is thought to be common in young children in
      developing countries and some data suggest that it may detrimentally affect
      children's development. OBJECTIVE: Our goal was to assess the effect of zinc
      supplementation on the developmental levels and behavior of Bangladeshi infants.
      DESIGN: This was a randomized, double-blind, controlled trial conducted in Dhaka,
      Bangladesh. Three hundred one infants aged 1 mo were randomly assigned to receive
      either 5 mg elemental Zn or placebo daily for 5 mo, and subsequent growth and
      morbidity were observed. For the present study, developmental levels were
      assessed in a subsample of 212 infants at 7 and 13 mo of age with use of the
      Bayley Scales of Infant Development, and the infants' behavior during the tests
      was observed. The children's social backgrounds, weights, and lengths were also
      recorded. RESULTS: The children's nutritional status was generally poor. The zinc
      treated group had slightly lower scores on the mental development index of the
      Bayley Scales than did the placebo group (beta = 3.7, SE = 1.3, P < 0.005). This
      effect remained significant when nutritional status and social background were
      controlled for. No other significant differences between groups were noted.
      CONCLUSIONS: The mental development index scores of the zinc-treated group were
      slightly but significantly lower than those of the placebo group. This finding
      may have been due to micronutrient imbalance. Caution should be exercised when
      supplementing undernourished infants with a single micronutrient.

PMID- 11522566
TI  - Antioxidant vitamin status and carotid atherosclerosis in the elderly.
AB  - BACKGROUND: The oxidative modification of LDL is thought to play a crucial role
      in the initiation of atherosclerosis. Antioxidant vitamins can protect LDL from
      oxidation, and high intakes or blood concentrations of these vitamins have been
      linked with a reduced risk of cardiovascular disease. Few data are available on
      the importance of antioxidant vitamins in earlier stages of atherogenesis.
      OBJECTIVE: We investigated the cross-sectional relation between antioxidant
      vitamin status and carotid atherosclerosis in a group of elderly persons. DESIGN:
      The study sample comprised 468 men and women aged 66-75 y living in Sheffield,
      United Kingdom. Duplex ultrasonography was used to measure intima-media thickness
      and the degree of stenosis in the extracranial carotid arteries. Antioxidant
      vitamin status was assessed by measuring fasting plasma concentrations of vitamin
      C, vitamin E, and beta-carotene. RESULTS: In the men, after adjustment for age
      and cardiovascular disease risk factors, a 20% higher plasma vitamin C
      concentration was associated with a 0.004-mm smaller intima-media thickness; a
      20% higher beta-carotene concentration was associated with a 0.005-mm smaller
      intima-media thickness. Compared with men with high blood concentrations of beta
      carotene or cholesterol-adjusted vitamin E, those with low blood concentrations
      of these vitamins were 2.5 times as likely to have carotid stenosis of >30%. We
      found no significant trends between plasma concentrations of antioxidant vitamins
      and either measure of carotid atherosclerosis in the women. CONCLUSION: A high
      antioxidant vitamin status may help to prevent the initiation and progression of
      early atherosclerotic lesions in men.

PMID- 11522565
TI  - Implementation of a 4-y, high-fiber, high-fruit-and-vegetable, low-fat dietary
      intervention: results of dietary changes in the Polyp Prevention Trial.
AB  - BACKGROUND: The Polyp Prevention Trial (PPT) was a multicenter randomized
      clinical trial designed to determine the effects of a high-fiber (4.30 g/MJ),
      high-fruit-and-vegetable (0.84 servings/MJ), low-fat (20% of energy from fat)
      diet on the recurrence of adenomatous polyps in the large bowel. OBJECTIVE: Our
      goal was to determine whether the PPT intervention plan could effect change in 3
      dietary goals and to examine the intervention's effect on the intake of other
      food groups and nutrients. DESIGN: Participants with large-bowel adenomatous
      polyps diagnosed in the past 6 mo were randomly assigned to either the
      intervention (n = 1037) or the control (n = 1042) group and remained in the trial
      for 4 y. Three dietary assessment instruments were used to measure dietary
      change: food-frequency questionnaires (in 100% of the sample), 4-d food records
      (in a 20% random cohort), and 24-h dietary recalls (in a 10% random sample).
      RESULTS: Intervention participants made and sustained significant changes in all
      PPT goals as measured by the dietary assessment instruments; the control
      participants' intakes remained essentially the same throughout the trial. The
      absolute differences between the intervention and control groups over the 4-y
      period were 9.7% of energy from fat (95% CI: 9.0%, 10.3%), 1.65 g dietary
      fiber/MJ (95% CI: 1.53, 1.74), and 0.27 servings of fruit and vegetables/MJ (95%
      CI: 0.25, 0.29). Intervention participants also reported significant changes in
      the intake of other nutrients and food groups. The intervention group also had
      significantly higher serum carotenoid concentrations and lower body weights than
      did the control group. CONCLUSION: Motivated, free-living individuals, given
      appropriate support, can make and sustain major dietary changes over a 4-y
      period.

PMID- 11522567
TI  - Cognitive performance and glucose.

PMID- 11522569
TI  - Dietary ratio of animal to vegetable protein and rate of bone loss and risk of
      fracture in postmenopausal women.

PMID- 11522571
TI  - Appearances may not be deceiving: calculation deficits due to a brain structure
      abnormality in neurologically normal children.

PMID- 11522572
TI  - Presurgical evaluation of epilepsy.
AB  - An overview of the following six cortical zones that have been defined in the
      presurgical evaluation of candidates for epilepsy surgery is given: the
      symptomatogenic zone; the irritative zone; the seizure onset zone; the
      epileptogenic lesion; the epileptogenic zone; and the eloquent cortex. The
      stepwise historical evolution of these different zones is described. The current
      diagnostic techniques used in the definition of these cortical zones, such as
      video-EEG monitoring, MRI and ictal single photon emission computed tomography,
      are discussed. Established diagnostic tests are set apart from procedures that
      should still be regarded as experimental, such as magnetoencephalography, dipole
      source localization and spike-triggered functional MRI. Possible future
      developments that might lead to a more direct definition of the epileptogenic
      zone are presented.

PMID- 11522573
TI  - Calculation difficulties in children of very low birthweight: a neural correlate.
AB  - Learning difficulties, including problems with numeracy, are common in Western
      populations. Many children with learning difficulty are survivors of preterm
      birth. Although some of these children have neurological disabilities, many are
      neurologically normal, and the latter group provides us with an important
      opportunity to investigate the neural bases of learning problems. We have
      conducted a neuroimaging study of adolescent children who had been born preterm
      at 30 weeks gestation or less, to investigate the relationship between brain
      structure and a specific difficulty in arithmetic calculation. Using voxel-based
      morphometry, we have been able to demonstrate that there is an area in the left
      parietal lobe where children without a deficit in calculation ability have more
      grey matter than those who do have this deficit. To our knowledge, this is the
      first report establishing a structural neural correlate of calculation ability in
      a group of neurologically normal individuals.

PMID- 11522574
TI  - Pathological laughter and crying: a link to the cerebellum.
AB  - Patients with pathological laughter and crying (PLC) are subject to relatively
      uncontrollable episodes of laughter, crying or both. The episodes occur either
      without an apparent triggering stimulus or following a stimulus that would not
      have led the subject to laugh or cry prior to the onset of the condition. PLC is
      a disorder of emotional expression rather than a primary disturbance of feelings,
      and is thus distinct from mood disorders in which laughter and crying are
      associated with feelings of happiness or sadness. The traditional and currently
      accepted view is that PLC is due to the damage of pathways that arise in the
      motor areas of the cerebral cortex and descend to the brainstem to inhibit a
      putative centre for laughter and crying. In that view, the lesions 'disinhibit'
      or 'release' the laughter and crying centre. The neuroanatomical findings in a
      recently studied patient with PLC, along with new knowledge on the neurobiology
      of emotion and feeling, gave us an opportunity to revisit the traditional view
      and propose an alternative. Here we suggest that the critical PLC lesions occur
      in the cerebro-ponto-cerebellar pathways and that, as a consequence, the
      cerebellar structures that automatically adjust the execution of laughter or
      crying to the cognitive and situational context of a potential stimulus, operate
      on the basis of incomplete information about that context, resulting in
      inadequate and even chaotic behaviour.

PMID- 11522575
TI  - Changes in brain activity related to eating chocolate: from pleasure to aversion.
AB  - We performed successive H(2)(15)O-PET scans on volunteers as they ate chocolate
      to beyond satiety. Thus, the sensory stimulus and act (eating) were held constant
      while the reward value of the chocolate and motivation of the subject to eat were
      manipulated by feeding. Non-specific effects of satiety (such as feelings of
      fullness and autonomic changes) were also present and probably contributed to the
      modulation of brain activity. After eating each piece of chocolate, subjects gave
      ratings of how pleasant/unpleasant the chocolate was and of how much they did or
      did not want another piece of chocolate. Regional cerebral blood flow was then
      regressed against subjects' ratings. Different groups of structures were
      recruited selectively depending on whether subjects were eating chocolate when
      they were highly motivated to eat and rated the chocolate as very pleasant
      [subcallosal region, caudomedial orbitofrontal cortex (OFC), insula/operculum,
      striatum and midbrain] or whether they ate chocolate despite being satiated
      (parahippocampal gyrus, caudolateral OFC and prefrontal regions). As predicted,
      modulation was observed in cortical chemosensory areas, including the insula and
      caudomedial and caudolateral OFC, suggesting that the reward value of food is
      represented here. Of particular interest, the medial and lateral caudal OFC
      showed opposite patterns of activity. This pattern of activity indicates that
      there may be a functional segregation of the neural representation of reward and
      punishment within this region. The only brain region that was active during both
      positive and negative compared with neutral conditions was the posterior
      cingulate cortex. Therefore, these results support the hypothesis that there are
      two separate motivational systems: one orchestrating approach and another
      avoidance behaviours.

PMID- 11522576
TI  - Inhibition of matrix metalloproteinases and tumour necrosis factor alpha
      converting enzyme as adjuvant therapy in pneumococcal meningitis.
AB  - Matrix metalloproteinases (MMPs) and tumour necrosis factor alpha (TNF-alpha)
      converting enzyme (TACE) contribute synergistically to the pathophysiology of
      bacterial meningitis. TACE proteolytically releases several cell-surface
      proteins, including the proinflammatory cytokine TNF-alpha and its receptors. TNF
      alpha in turn stimulates cells to produce active MMPs, which facilitate leucocyte
      extravasation and brain oedema by degradation of extracellular matrix components.
      In the present time-course studies of pneumococcal meningitis in infant rats, MMP
      8 and -9 were 100- to 1000-fold transcriptionally upregulated, both in CSF cells
      and in brain tissue. Concentrations of TNF-alpha and MMP-9 in CSF peaked 12 h
      after infection and were closely correlated. Treatment with BB-1101 (15 mg/kg
      subcutaneously, twice daily), a hydroxamic acid-based inhibitor of MMP and TACE,
      downregulated the CSF concentration of TNF-alpha and decreased the incidences of
      seizures and mortality. Therapy with BB-1101, together with antibiotics,
      attenuated neuronal necrosis in the cortex and apoptosis in the hippocampus when
      given as a pretreatment at the time of infection and also when administration was
      started 18 h after infection. Functionally, the neuroprotective effect of BB-1101
      preserved learning performance of rats assessed 3 weeks after the disease had
      been cured. Thus, combined inhibition of MMP and TACE offers a novel therapeutic
      strategy to prevent brain injury and neurological sequelae in bacterial
      meningitis.

PMID- 11522577
TI  - The expression profile of matrix metalloproteinases (MMPs) and their inhibitors
      (TIMPs) in lesions and normal appearing white matter of multiple sclerosis.
AB  - In multiple sclerosis, matrix metalloproteinases (MMPs) are effectors of crucial
      pathogenetic steps, such as blood-brain barrier breakdown, invasion of brain
      parenchyma by immune cells and demyelination. However, only limited data are
      available on the types of MMPs induced in the course of multiple sclerosis, and
      on the role of their endogenous antagonists, the tissue inhibitors of
      metalloproteinases (TIMPs). We quantified the transcriptional expression of six
      MMPs and the four TIMPs in lesions and in normal appearing white matter (NAWM)
      from post-mortem multiple sclerosis brain tissue by real-time polymerase chain
      reaction, and compared levels with those in brain tissue from six control
      patients without neurological disease. The mRNA expression of MMP-7 and -9, but
      not of other metalloproteinases [MMP-2 and -3, and tumour necrosis factor (TNF)
      alpha-converting-enzyme] was equally upregulated throughout all stages of lesion
      formation with active inflammation, and in most of matched NAWM tissue. The
      transcription of cytokines TNF-alpha/beta and IL (interleukin)-2, known
      modulators of MMPs, was upregulated only in distinct stages of lesion formation,
      while their receptors were not induced at all, which suggests that additional
      signalling molecules participate in the sustained upregulation of MMP-7 and -9 in
      multiple sclerosis. None of the TIMPs showed a significant induction over
      baseline expression of controls. We hypothesize that an imbalance between MMP and
      TIMP expression may cause a persistent proteolytic overactivity in multiple
      sclerosis, that may be a factor for continuous tissue destruction, and hence for
      secondary disease progression.

PMID- 11522578
TI  - Roles of capsaicin-insensitive nociceptors in cutaneous pain and secondary
      hyperalgesia.
AB  - Polymodal nociceptors respond to mechanical, thermal and chemical stimuli.
      Whereas sensitivities to heat and to the irritant substance capsaicin have
      recently been linked via the properties of the vanilloid receptor type 1 receptor
      ion channel, sensitivity to noxious mechanical stimuli such as the pinpricks used
      in clinical neurology seems to be unrelated. We investigated the peripheral
      neural basis of pinprick pain using quantitative psychophysical techniques
      combined with selective conduction block by nerve compression and selective
      desensitization by topical capsaicin treatment. Complete A-fibre block by
      compression of the superficial radial nerve (criterion: loss of first pain
      sensation) lowered the stimulus-response function for pinprick pain (-82 +/- 6%
      versus baseline). Topical pretreatment of the skin with a 10% capsaicin cream
      also lowered the pinprick stimulus-response function (-32 +/- 10%), whereas laser
      evoked heat pain was eliminated completely (-96 +/- 2%). Under combined capsaicin
      desensitization and A-fibre blockade, pinprick pain was eliminated completely (
      98 +/- 1%). Intradermal injection of 40 microg capsaicin into normal skin between
      two skin areas that had been pretreated with either capsaicin cream or vehicle
      produced secondary hyperalgesia with a 260% enhancement of the stimulus-response
      function for pinprick pain in both areas. In contrast, axon reflexive flare
      spread only into the vehicle-treated area. These results suggest that capsaicin
      sensitive afferents, including polymodal A-fibre and C-fibre nociceptors, make a
      small contribution to pinprick pain and that capsaicin-insensitive C-fibres do
      not contribute significantly to either mechanical or heat pain. Pinprick pain is
      mediated primarily by capsaicin-insensitive A-fibre nociceptors, which include
      high-threshold mechanoreceptors and type I mechano-heat nociceptors. In addition,
      central sensitization to input from these A-fibre nociceptors is the primary
      mechanism that accounts for the enhanced pain in response to punctate mechanical
      stimuli in the zone of secondary hyperalgesia. These capsaicin-insensitive A
      fibre nociceptors may also mediate hyperalgesia in neuropathic pain.

PMID- 11522579
TI  - Arm tremor in cervical dystonia differs from essential tremor and can be
      classified by onset age and spread of symptoms.
AB  - The pathophysiology of arm tremor in patients with cervical dystonia (CD) and its
      relationship to other types of tremor is unclear. In the present study, we have
      compared the tremor in these patients with that seen in patients with essential
      tremor (ET) using two neurophysiological techniques: the triphasic EMG pattern
      accompanying ballistic wrist flexion movements; and reciprocal inhibition between
      forearm muscles. During ballistic wrist flexion movements, the latency of the
      second agonist EMG burst was later in ET than CD patients. This suggests that the
      mechanism of the arm tremor in CD may differ from that in ET. There was no group
      difference between reciprocal inhibition in patients with ET or CD. However,
      there was much more variability in the data from patients with CD. Because of
      this, we subdivided the CD patients into two groups, group A with normal levels
      of presynaptic inhibition and group B with reduced or absent presynaptic
      inhibition. A posteriori, it turned out that the patients in these two subgroups
      had similar clinical symptoms, but different clinical histories. The arm tremor
      of patients in group A started simultaneously with torticollis (mean onset age of
      arm tremor 40 years +/- 20.7 SD, interval between onset of arm tremor and
      torticollis 0 +/- 2.9 years) whereas it began much earlier (mean onset age 14
      years +/- 6 SD) and preceded onset of torticollis by a longer interval (21.6 +/-
      17.5 years) in patients of group B. Patients in group A also had less co
      contraction in their ballistic wrist movements between the first agonist and the
      antagonist burst than those patients in group B. We conclude that arm tremor in
      patients with CD may have a mechanism different from that seen in patients with
      ET. Moreover, the data imply that there are two subgroups of CD patients with arm
      tremor, one with a late and simultaneous onset of arm tremor and torticollis
      (group A), and another with an early onset of arm tremor and later development of
      torticollis (group B). These groups do not correspond to the currently proposed
      clinical subdivision of 'dystonic tremor' and 'tremor associated with dystonia'.

PMID- 11522580
TI  - The subthalamic nucleus in Parkinson's disease: somatotopic organization and
      physiological characteristics.
AB  - Single-cell recording of the subthalamic nucleus (STN) was undertaken in 14
      patients with Parkinson's disease submitted to surgery. Three hundred and fifty
      neurones were recorded and assessed for their response to passive and active
      movements. Thirty-two per cent were activated by passive and active movement of
      the limbs, oromandibular region and abdominal wall. All neurones with
      sensorimotor responses were in the dorsolateral region of the STN. Arm-related
      neurones were lateral (> or =14 mm plane) to leg-related neurones, which were
      found more medially (< or =12 mm). Representation of the oromandibular
      musculature was in the middle of the sensorimotor region (approximately 13 mm
      plane) and ventral to the arm and leg. Two hundred neurones were adequately
      isolated for 'off-line' analysis. The mean frequency of discharge was 33 +/- 17
      Hz (13-117 Hz). Three types of neuronal discharges were distinguished: irregular
      (60.5%), tonic (24%) and oscillatory (15.5 %). They were statistically
      differentiated on the basis of their mean firing frequency and the coefficient of
      variation of the interspike interval. Neurones responding to movement were of the
      irregular or tonic type, and were found in the dorsolateral region of the STN.
      Neurones with oscillatory and low frequency activity did not respond to movement
      and were in the ventral one-third of the nucleus. Thirty-eight tremor-related
      neurones were recorded. The majority (84%) of these were sensitive to movement
      and were located in the dorsolateral region of the STN. Cross power analysis (n =
      16) between the rhythmic neuronal activity and tremor in the limbs showed a peak
      frequency of 5 Hz (4-8 Hz). Neuronal activity of the substantia nigra pars
      reticulata was recorded 0.5-3 mm below the STN. Eighty neurones were recorded 'on
      line' and 27 were isolated for 'off-line' analysis. A tonic pattern of discharge
      characterized by a mean firing rate of 71 +/- 28 Hz (35-122 Hz) with a mean
      coefficient of variation of the interspike interval of 0.85 +/- 0.29 ms was
      found. In only three neurones (11%) was there a response to sensorimotor
      stimulation. The findings of this study indicate that the somatotopic arrangement
      and electrophysiological features of the STN in Parkinson's disease patients are
      similar to those found in monkeys.

PMID- 11522581
TI  - Suppression of experimental autoimmune neuritis by leflunomide.
AB  - Leflunomide is a new immunosuppressive drug whose active metabolite, A77 1726,
      impairs cellular nucleotide metabolism by inhibiting the dihydroorotate
      dehydrogenase (DHODH), a rate-limiting enzyme of de novo pyrimidine synthesis.
      Furthermore, A77 1726 suppresses tyrosine kinases involved in signal transduction
      pathways. We investigated the immunosuppressive effects of leflunomide in
      experimental autoimmune neuritis (EAN) in rats, which is a model of immune
      mediated neuropathies. In EAN that was actively induced by subcutaneous injection
      of peripheral nerve myelin, leflunomide completely prevented paraparesis if
      applied orally from the day of immunization. Leflunomide was much more effective
      than azathioprine, which did not mitigate EAN at all. Even when leflunomide was
      administered therapeutically after the appearance of the first neuropathical
      signs, it halted the progression and markedly reduced the severity and duration
      of EAN. Inflammatory infiltrates, demyelination and axonal degeneration in
      sciatic nerve sections of leflunomide-treated EAN rats were strongly reduced.
      Leflunomide-treated rats did not mount autoantibodies as specified by ELISA
      (enzyme-linked immunosorbent assay) with a mixture of peripheral myelin proteins,
      including P2 and myelin basic protein. In EAN that was adoptively transferred by
      injection of neuritogenic cells of a P2-specific T-helper line, application of
      leflunomide also clearly reduced signs of disease. Additional injection of
      uridine did not neutralize the effect of leflunomide. Similarly, transfer of
      neuritogenic P2-specific T cells, which were activated in the presence of A77
      1726 plus uridine in vitro, still resulted in reduced severity of adoptive
      transfer EAN in vivo, although proliferation of these cells in vitro was
      identical to that of control cells. The T-cell receptor-mediated in vitro
      activatability of a P2-specific T-cell hybridoma was diminished by high
      concentrations of A77 1726, as evidenced by reduced Ca(2+) flux into the cytosol.
      Together with the findings in adoptive transfer EAN, this indicates that the
      antiproliferative effect is probably not the only mechanism of immunosuppressive
      action by leflunomide. In summary, leflunomide suppresses EAN efficiently and may
      constitute a promising therapy for immune-mediated neuropathies.

PMID- 11522582
TI  - Short-term brain volume change in relapsing-remitting multiple sclerosis: effect
      of glatiramer acetate and implications.
AB  - The assessment of brain volume change with serial MRI provides an objective
      measure of an important component of the pathology of multiple sclerosis.
      Glatiramer acetate (GA) has a beneficial effect on clinical and MRI measures of
      disease activity and burden in patients with relapsing-remitting (RR) multiple
      sclerosis. This study investigated the impact of GA treatment on the development
      of brain atrophy in RR multiple sclerosis patients. The study consisted of a 9
      month, double-blind, placebo-controlled phase followed by a 9-month open-label
      phase. Patients were randomized to receive either 20 mg GA or placebo by daily
      subcutaneous injections and underwent brain MRI scans every month during the
      first phase, and every 3 months during the second phase of the study. Using a
      semi-automated segmentation technique based on local thresholding, brain volume
      was measured from seven contiguous periventricular slices from the scans obtained
      at baseline, the end of the double-blind phase and the end of the study. From the
      original trial cohort, image sets from 113 out of 119 patients randomized to GA,
      and 114 out of 120 randomized to placebo treatment were evaluated. Brain volume
      was significantly correlated with patients' disability at each time-point. No
      significant differences between placebo- and GA-treated patients were found for
      baseline brain volume and rate of brain volume change over the study, even though
      a possible late trend for treatment with GA to retard the loss of brain volume
      was observed. There was a significant, but modest, correlation between MRI
      activity during the double-blind phase, and brain volume change over the entire
      study among patients originally treated with placebo. The modest correlation
      between enhancement frequency and brain atrophy loss indicates that the
      suppression of inflammatory activity in RR multiple sclerosis patients is not
      fully and rapidly associated with a similar effect on the global
      neurodegenerative processes. This study also suggests that any effect of GA in
      preventing brain volume decrease is not evident early following institution of
      treatment.

PMID- 11522583
TI  - Size-selective neuronal changes in the anterior optic pathways suggest a
      differential susceptibility to injury in multiple sclerosis.
AB  - Axonal damage is found in both acute and chronic lesions of multiple sclerosis.
      Direct axon counting in post-mortem tissue has suggested that smaller axons might
      have a greater susceptibility to damage, but methodological limitations have
      precluded unequivocal interpretation. However, as neuronal and axonal sizes are
      linked and neuronal changes would be expected with retrograde or transsynaptic
      degeneration following axon injury, we hypothesized that an alternative strategy
      for studying this phenomenon would be to define multiple sclerosis-associated
      changes in neurones. To test this hypothesis, we measured both axonal loss and
      neuronal size changes in the anterior optic pathway [including the optic nerve
      (ON), optic tract (OT) and lateral geniculate nucleus] of the brains of eight
      patients who died with multiple sclerosis and in eight control brains. The ONs
      and OTs in brains from the multiple sclerosis patients showed a trend to smaller
      mean cross-sectional areas (ON, multiple sclerosis = 6.84 mm(2), controls = 9.25
      mm(2); and OT, multiple sclerosis = 6.45 mm(2), controls = 7.94 mm(2), P = 0.08)
      and had reduced axonal densities (ON, multiple sclerosis = 1.1 x 10(5)/mm(2),
      controls = 1.7 x 10(5)/mm(2); and OT, multiple sclerosis = 1.4 x 10(5)/mm(2),
      controls = 1.8 x 10(5)/mm(2), P = 0.006). Estimated total axonal counts were
      reduced by 32 (OT)-45% (ON) in the patients relative to controls (ON, multiple
      sclerosis = 8.1 x 10(5) axons, controls = 14.8 x10(5), P = 0.05; and OT, multiple
      sclerosis = 9.1 x 10(5), controls = 13.3 x 10(5), P = 0.02). The size
      distributions of the magnocellular cells in the lateral geniculate nucleus were
      similar for the two groups, but in multiple sclerosis brains the parvocellular
      cells were significantly smaller (mean sizes: multiple sclerosis = 226 microm(2),
      controls = 230 microm(2), P < 0.001) and had a larger variation in size,
      suggesting a greater proportion of atrophic neurones. Axon loss in the optic
      nerves of multiple sclerosis patients correlated strongly with measures of
      increased dispersion of cell sizes in the parvocellular layer (r = 0.8, P <
      0.04). These data demonstrate that both atrophy and decreased density contribute
      to the substantial axonal loss in the anterior visual pathway of these patients.
      This appears related to a relatively selective atrophy of the smaller neurones of
      the parvocellular layer in the lateral geniculate nucleus, supporting the
      hypothesis that smaller axons may be preferentially susceptible to injury in
      multiple sclerosis.

PMID- 11522584
TI  - Macrophagic myofasciitis lesions assess long-term persistence of vaccine-derived
      aluminium hydroxide in muscle.
AB  - Macrophagic myofasciitis (MMF) is an emerging condition of unknown cause,
      detected in patients with diffuse arthromyalgias and fatigue, and characterized
      by muscle infiltration by granular periodic acid-Schiff's reagent-positive
      macrophages and lymphocytes. Intracytoplasmic inclusions have been observed in
      macrophages of some patients. To assess their significance, electron microscopy
      was performed in 40 consecutive cases and chemical analysis was done by
      microanalysis and atomic absorption spectrometry. Inclusions were constantly
      detected and corresponded to aluminium hydroxide, an immunostimulatory compound
      frequently used as a vaccine adjuvant. A lymphocytic component was constantly
      observed in MMF lesions. Serological tests were compatible with exposure to
      aluminium hydroxide-containing vaccines. History analysis revealed that 50 out of
      50 patients had received vaccines against hepatitis B virus (86%), hepatitis A
      virus (19%) or tetanus toxoid (58%), 3-96 months (median 36 months) before
      biopsy. Diffuse myalgias were more frequent in patients with than without an MMF
      lesion at deltoid muscle biopsy (P < 0.0001). Myalgia onset was subsequent to the
      vaccination (median 11 months) in 94% of patients. MMF lesion was experimentally
      reproduced in rats. We conclude that the MMF lesion is secondary to intramuscular
      injection of aluminium hydroxide-containing vaccines, shows both long-term
      persistence of aluminium hydroxide and an ongoing local immune reaction, and is
      detected in patients with systemic symptoms which appeared subsequently to
      vaccination.

PMID- 11522585
TI  - Evidence for subcortical involvement in the visual control of human reaching.
AB  - To test whether the most rapid visually evoked reach adjustments are cortically
      organized in humans, we have measured their latency in a healthy subject with
      complete agenesis of the corpus callosum. This condition precludes direct
      communication between left and right cerebral cortices and so, in this subject, a
      purely cortical visuomotor process would be expected to produce longer-latency
      responses to a target that appears in the visual hemifield contralateral to the
      responding limb (crossed) compared with the ipsilateral hemifield (uncrossed). As
      predicted, when performing simple reaction time tasks that involved lifting a
      finger or an arm in response to a visual stimulus presented to either hemifield,
      this acallosal subject showed a significant crossed-uncrossed latency difference
      (mean 35.8 ms) that was not present in control subjects (group mean 2.2 ms). In
      contrast, when she reached for a target that unexpectedly jumped into either
      visual hemifield, the latencies of mid-flight adjustment were the same
      (approximately 120 ms) irrespective of either the target jump direction or which
      hand was used. This was not due to an early movement of the eyes bringing the
      target back on to the fovea since this subject's finger always deviated towards
      the new target position in advance of her eyes. Neither could it be explained by
      the use of ipsilateral corticospinal projections since transcranial magnetic
      stimulation over the motor cortex failed to evoke ipsilateral responses in arm or
      hand muscles. These results suggest that, even in humans, subcortical structures
      are involved in the fastest adjustments of the reaching arm made in response to
      fresh visual information. An additional finding in this subject was that, when
      reaching, the eye saccadic latency was greater by 36 ms on average when the
      target jumped right compared with left, irrespective of which hand was being
      used. This is the same value as the mean interhemispheric transfer time obtained
      in the simple reaction time tasks and may indicate right-hemispheric dominance
      for saccadic eye movement control.

PMID- 11522586
TI  - Material-specific lateralization in the medial temporal lobe and prefrontal
      cortex during memory encoding.
AB  - Numerous observations in patients with unilateral lesions of the medial temporal
      lobe (MTL) and the prefrontal cortex indicate that memory processes are
      lateralized according to content. Left-sided lesions interfere with verbal memory
      processes, whereas right-sided lesions interfere with visuospatial (non-verbal)
      memory processes. However, functional imaging studies have resulted in
      contradictory data, some studies showing lateralization in the prefrontal cortex
      determined by stage of processing (encoding versus retrieval) and others
      suggesting that lateralization is dependent on the type of material. Few studies
      have examined this issue in the MTL. In order to test the hypothesis that the
      lateralization of encoding processes in the MTL and frontal regions is dependent
      on the verbalizability of the material, we performed behavioural and functional
      imaging studies. We demonstrated differing verbalizabilities of three classes of
      non-verbal stimuli (scenes > faces > abstract patterns) using a dual-task verbal
      interference behavioural paradigm. A functional neuroimaging study of encoding
      was carried out using these three types of stimuli, plus words. During whole
      brain functional MRI at 1.5 T, eight normal right-handed adults were presented
      with alternating blocks of novel and repeated stimuli under intentional memory
      encoding conditions. Verbal encoding resulted in left-lateralized activation of
      the inferior prefrontal cortex and the MTL. Pattern encoding activated the right
      inferior prefrontal cortex and the right MTL. Scenes and faces resulted in
      approximately symmetrical activation in both regions. The data indicate that the
      lateralization of encoding processes is determined by the verbalizability of
      stimuli.

PMID- 11522587
TI  - Adenosine-mediated inhibition of striatal GABAergic synaptic transmission during
      in vitro ischaemia.
AB  - Several reports have shown that energy deprivation, as a result of hypoxia,
      hypoglycaemia or ischaemia, depresses excitatory synaptic transmission in
      virtually all brain areas. How this pathological condition affects inhibitory
      synaptic transmission is still unclear. In the present in vitro study, we coupled
      whole-cell patch clamp recordings from striatal neurones with focal stimulation
      of GABAergic nerve terminals in order to characterize the electrophysiological
      effects of combined oxygen and glucose deprivation (in vitro ischaemia) on
      inhibitory postsynaptic currents (IPSCs) in this brain area. We found that brief
      periods (2-5 min) of in vitro ischaemia invariably caused a marked depression of
      IPSC amplitude. This inhibitory effect was fully reversible on removal of the
      ischaemic challenge. It was coupled with an increased paired-pulse facilitation,
      suggesting the involvement of presynaptic mechanisms. Accordingly, the ischaemic
      inhibition of striatal GABAergic IPSCs was not caused by a shift in the reversal
      potential of GABA(A)-receptor mediated synaptic currents, and was independ- ent
      of postsynaptic ATP concentrations. Endogenous adenosine, acting on A1 receptors,
      appeared responsible for this presynaptic action as the ischaemic depression of
      IPSCs was prevented by CPT [8-(4-chlorophenylthio) adenosine] and DPCPX, two
      adenosine A1 receptor antagonists, and mimicked by the application of adenosine
      in the bathing solution. Conversely, ATP-sensitive potassium channels were not
      involved in the inhibition of IPSCs by ischaemia, as demonstrated by the fact
      that tolbutamide and glipizide, two blockers of these channels, were ineffective
      in preventing this electrophysiological effect. The early depression of GABA
      mediated synaptic transmission might play a role in the development of
      irreversible neuronal injury in the course of brain ischaemia.

PMID- 11522588
TI  - The course of corticofacial projections in the human brainstem.
AB  - Transcranial magnetic stimulation was used to investigate the corticofacial
      projections in 53 patients with (n = 28) and without (n = 25) central facial
      paresis due to unifocal ischaemic lesions at different brainstem levels. Lesion
      topography documented by MRI studies was correlated with the electrophysiological
      findings. In the majority of patients the corticofacial fibres travel within the
      ventromedial base of the pons and cross the midline at the level of the facial
      nucleus. In some individuals, however, we found evidence that corticolingual
      fibres form an 'aberrant bundle' in a paralemniscal position at the dorsal edge
      of the pontine base. In other patients the corticofacial fibres loop down into
      the ventral part of the upper medulla, cross the midline and ascend in the
      dorsolateral medullary region ipsilaterally to the facial nucleus. The findings
      suggest that facial paresis due to a brainstem lesion may present as
      contralateral supranuclear facial paresis by a lesion of the cerebral peduncle,
      pontine base, the aberrant bundle and the ventral medulla. Supranuclear facial
      paresis ipsilateral to the lesion side may result from a lesion in the lateral
      medulla, and facial paresis of the supranuclear type may be imitated by a lesion
      of the peripheral facial nerve in the dorsolateral medulla with involvement of
      the lower pons.

PMID- 11522590
TI  - Suppression of K(+)-induced hyperpolarization by phenylephrine in rat mesenteric
      artery: relevance to studies of endothelium-derived hyperpolarizing factor.
AB  - In intact mesenteric arteries, increasing [K(+)]o by 5 mM hyperpolarized both
      endothelial and smooth muscle cells. Subsequent exposure to 10 microM
      phenylephrine depolarized both cell types which were then repolarized by a 5 mM
      increase in [K(+)]o. In endothelium-denuded vessels, increasing [K(+)]o by 5 mM
      hyperpolarized the smooth muscle but K(+) had no effect after depolarization by
      10 microM phenylephrine. On subsequent exposure to iberiotoxin plus 4
      aminopyridine, the repolarizing action of 5 mM K(+) was restored. In endothelium
      intact vessels exposed to phenylephrine, pretreatment with a gap junction
      inhibitor (gap 27) reduced K(+)-mediated smooth muscle repolarization without
      affecting the endothelial cell response. It is concluded that phenylephrine
      induced efflux of K(+) via smooth muscle K(+) channels produces a local increase
      in [K(+)]o which impairs repolarization to added K(+). Thus, studies involving
      vessels precontracted with agonists which increase [K(+)]o maximize the role of
      gap junctions and minimize any contribution to the EDHF pathway from endothelium
      derived K(+).

PMID- 11522591
TI  - Assessment of agonism at G-protein coupled receptors by phosphatidic acid and
      lysophosphatidic acid in human embryonic kidney 293 cells.
AB  - Several different molecular species of phosphatidic acid (PA) bind to a G-protein
      coupled receptor (GPCR) to induce activation of the p42/p44 mitogen-activated
      protein kinase (p42/p44 MAPK) pathway in HEK 293 cells. PA is active at low
      nanomolar concentrations and the response is sensitive to pertussis toxin (which
      uncouples GPCRs from G(i/o)). The de-acylated product of PA, lysophosphatidic
      acid (LPA), which binds to members of the endothelial differentiation gene (EDG)
      family of receptors also stimulated p42/p44 MAPK in a pertussis toxin sensitive
      manner, but with an approximately 100 - 1000 fold lower potency compared with the
      different molecular species of PA. RT - PCR using gene-specific primers showed
      that HEK 293 cells express EDG2 and PSP24, the latter being a lipid binding GPCR
      out with the EDG cluster. We conclude that PA is a novel high potency GPCR
      agonist.

PMID- 11522592
TI  - Effects and mechanisms of emodin on cell death in human lung squamous cell
      carcinoma.
AB  - 1. Emodin (1,3,8-trihydroxy-6-methylanthraquinone) is an active component from
      the root and rhizome of Rheum palmatum that has been reported to exhibit
      antitumour effects, but the mechanism is not known. The study investigated the
      effects and mechanisms of emodin-induced cell death in human lung squamous
      carcinoma cell line CH27. 2. Emodin (50 microM)-induced CH27 cell apoptosis was
      confirmed by cell morphological change, sub-G1 formation in flow cytometry
      analysis, viability assay and degradation of focal adhesion kinase in this study.
      3. Emodin-induced apoptosis of CH27 cells does not involve modulation of
      endogenous Bcl-X(L) protein expression, but appears to be associated with the
      increased expression of cellular Bak and Bax proteins. This study also
      demonstrated the translocation of Bak and Bax from cytosolic to particulate
      fractions. 4. This study has shown that emodin-treated CH27 cells revealed the
      increases in the relative abundance of cytochrome c for the indicated time
      intervals in cytosolic fraction. 5. This study demonstrates that the activation
      of caspase-3, caspase-9 and caspase-8 is an important determinant of apoptotic
      death induced by emodin. 6. These results suggested that emodin induces CH27 cell
      death by Bax death pathway and Fas pathway.

PMID- 11522593
TI  - Effect of M40403 treatment of diabetic rats on endoneurial blood flow, motor
      nerve conduction velocity and vascular function of epineurial arterioles of the
      sciatic nerve.
AB  - 1. To further explore the effect of antioxidants in preventing diabetes-induced
      vascular and neural dysfunction we treated streptozotocin-induced diabetic rats
      daily with subcutaneous injections of 10 mg kg(-1) of M40403 (n=11) and compared
      the results obtained from 17 control rats and 14 untreated diabetic rats. M40403
      is a manganese(II) complex with a bis(cyclo-hexylpyridine)-substituted
      macrocyclic ligand that was designed to be a selective functional mimetic of
      superoxide dismutase. Thus, M40403 provides a useful tool to evaluate the roles
      of superoxide in disease states. 2. Treatment with M40403 significantly improved
      diabetes-induced decrease in endoneurial blood flow, acetylcholine-mediated
      vascular relaxation in arterioles that provide circulation to the region of the
      sciatic nerve, and motor nerve conduction velocity (P<0.05). M40403 treatment
      also reduced the appearance of superoxide in the aorta and epineurial vessels and
      peroxynitrite in epineurial vessels. Treating diabetic rats with M40403 reduced
      the diabetes-induced increase in thiobarbituric acid reactive substances in serum
      but did not prevent the decrease in lens glutathione level. Treating diabetic
      rats with M40403 did not improve sciatic nerve Na(+)/K(+) ATPase activity or the
      sorbitol, fructose or myo-inositol content of the sciatic nerve. 3. These studies
      provide additional evidence that diabetes-induced oxidative stress and the
      generation of superoxide and perhaps peroxynitrite may be partially responsible
      for the development of diabetic vascular and neural complications.

PMID- 11522594
TI  - A possible role of lipoxygenase in the activation of vanilloid receptors by
      anandamide in the guinea-pig bronchus.
AB  - 1. In the absence of indomethacin, anandamide did not contract the guinea-pig
      bronchus at concentrations up to 100 microM. In the presence of indomethacin (10
      microM), anandamide induced concentration-related contractions with a pEC(50)
      value of 5.18+/-0.11. It was significantly less potent than capsaicin (pEC(50)
      7.01+/-0.1). The anandamide uptake inhibitor AM404, produced only a 14.1+/-3.22%
      contraction at 100 microM. All experiments were conducted in the presence of PMSF
      (20 microM). 2. The vanilloid receptor antagonist, capsazepine (10 microM),
      significantly attenuated the contractile effect of anandamide, the response to
      100 microM anandamide being 40.53+/-7.04% in the presence of vehicle and 1.57+/
      8.93% in the presence of 10 microM capsazepine. The contractile actions of
      anandamide and AM404 were markedly enhanced by the peptidase inhibitor thiorphan.
      3. The log concentration-response curve of anandamide was unaltered by the CB1
      receptor antagonist, SR141716A. The pEC(50) values for anandamide were 4.88+/
      0.08 and 5.17+/-0.19 in the presence of vehicle and SR141716A (1 microM)
      respectively. 4. The lipoxygenase inhibitors 5,8,11,14-eicosatetraynoic acid
      (ETYA) and 5,8,11 eicosatriynoic acid (ETI) reduced the effect of 100 microM
      anandamide from 34.7+/-1.9% (vehicle) to 7.7+/-5% (ETYA, 10 microM) and from
      41.85+/-4.25% (n=6) (vehicle) to 10.31+/-3.54 (n=6) (ETI, 20 microM). Neither
      inhibitor significantly affected contraction of the tissue by substance P. 5.
      This study provides evidence that anandamide acts on vanilloid receptors in the
      guinea-pig isolated bronchus. These data raise the possibility that the
      contractile action of anandamide may be due, at least in part, to lipoxygenase
      metabolites of this fatty acid amide that are vanilloid receptor agonists.

PMID- 11522595
TI  - Angiotensin II reduces infarct size and has no effect on post-ischaemic
      contractile dysfunction in isolated rat hearts.
AB  - 1. In order to test the hypothesis that angiotensin II exacerbates myocardial
      ischaemia-reperfusion (IR) injury, we examined the effects of graded angiotension
      II concentrations of angiotensin II on IR injury in both working and non-working
      (Langendorff) isolated rat hearts. 2. Non-working hearts were subjected to 30 min
      aerobic perfusion (baseline) then 25 min of global, no-flow ischaemia followed by
      30 min of reperfusion either in the absence (control, n=7) or presence of 1 (n=6)
      or 10 nM (n=5) angiotensin II). Recoveries of LV developed pressure and coronary
      flow after 30 min reperfusion in control hearts (58+/-9 and 40+/-8% of baseline
      levels, respectively) were no different from hearts treated with 1 or 10 nM
      angiotensin II. Infarct size (determined at the end of reperfusion by
      triphenyltetrazolium chloride staining) was reduced by angiotensin II in a
      concentration-dependent manner (from a control value of 27+/-3 to 18+/-4% and 9+/
      3% of the LV, respectively). 3. Working hearts were subjected to 50 min pre
      ischaemic (pre-I) aerobic perfusion then 30 min of global, no-flow ischaemia
      followed by 30 min of reperfusion either in the absence (control, n=14) or
      presence of 1 (n=8), 10 (n=7) or 100 nM (n=7) angiotensin II). In controls, post
      ischaemic (post-I) left ventricular (LV) work and efficiency of oxygen
      consumption were depressed (43+/-9 and 42+/-10% of pre-I levels, respectively).
      The presence of angiotensin II throughout IR had no effect on LV work compared
      with control. 4. Thus, angiotensin II reduces infarct size in a concentration
      dependent manner but has no effect on contractile stunning associated with IR in
      isolated rat hearts.

PMID- 11522596
TI  - The mechanisms involved in the long-lasting neuroprotective effect of fluoxetine
      against MDMA ('ecstasy')-induced degeneration of 5-HT nerve endings in rat brain.
AB  - 1. It has been reported that co-administration of fluoxetine with 3,4
      methylenedioxymethamphetamine (MDMA, 'ecstasy') prevents MDMA-induced
      degeneration of 5-HT nerve endings in rat brain. The mechanisms involved have now
      been investigated. 2. MDMA (15 mg kg(-1), i.p.) administration produced a
      neurotoxic loss of 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) in cortex,
      hippocampus and striatum and a reduction in cortical [3H]-paroxetine binding 7
      days later. 3. Fluoxetine (10 mg kg(-1), i.p., x2, 60 min apart) administered
      concurrently with MDMA or given 2 and 4 days earlier provided complete
      protection, and significant protection when given 7 days earlier. Fluvoxamine (15
      mg kg(-1), i.p., x2, 60 min apart) only produced neuroprotection when
      administered concurrently. Fluoxetine (10 mg kg(-1), x2) markedly increased the
      K(D) and reduced the B(max) of cortical [3H]-paroxetine binding 2 and 4 days
      later. The B(max) was still decreased 7 days later, but the K(D) was unchanged.
      [3H]-Paroxetine binding characteristics were unchanged 24 h after fluvoxamine (15
      mg kg(-1), x2). 4. A significant cerebral concentration of fluoxetine plus
      norfluoxetine was detected over the 7 days following fluoxetine administration.
      The fluvoxamine concentration had decreased markedly by 24 h. 5. Pretreatment
      with fluoxetine (10 mg kg(-1), x2) failed to alter cerebral MDMA accumulation
      compared to saline pretreated controls. 6. Neither fluoxetine or fluvoxamine
      altered MDMA-induced acute hyperthermia. 7. These data demonstrate that
      fluoxetine produces long-lasting protection against MDMA-induced
      neurodegeneration, an effect apparently related to the presence of the drug and
      its active metabolite inhibiting the 5-HT transporter. Fluoxetine does not alter
      the metabolism of MDMA or its rate of cerebral accumulation.

PMID- 11522597
TI  - Suppression of granulocyte/macrophage colony-stimulating factor release from
      human monocytes by cyclic AMP-elevating drugs: role of interleukin-10.
AB  - 1. Granulocyte/macrophage colony-stimulating factor (GM-CSF) is a pro
      inflammatory cytokine secreted by cells of the monocyte/macrophage lineage and
      has been implicated in the pathogenesis of bronchitis and asthma. 2. In the
      present study we have evaluated the effect of several cyclic AMP-elevating agents
      on lipopolysaccharide (LPS)-induced GM-CSF release from human monocytes and the
      extent to which the anti-inflammatory cytokine, interleukin (IL)-10, is involved.
      3. LPS evoked a concentration-dependent generation of GM-CSF from human monocytes
      that was inhibited, at the mRNA and protein level, by 8-Br-cyclic AMP, cholera
      toxin, prostaglandin E2 (PGE2) and a number of structurally dissimilar
      phosphodiesterase (PDE) 4 inhibitors. 4. Pre-treatment of monocytes with a
      concentration of an anti-IL-10 monoclonal antibody that abolished the inhibitory
      action of a maximally effective concentration of exogenous human recombinant IL
      10, significantly augmented LPS-induced GM-CSF generation. This effect was
      associated with a parallel upwards displacement of the concentration-response
      curves that described the inhibition of GM-CSF by PGE2, 8-Br-cyclic AMP and the
      PDE4 inhibitor, rolipram, without significantly changing the potency of any drug.
      Consequently, the maximum percentage inhibition of GM-CSF release was reduced.
      Further experiments established that the reduction in the maximum inhibition of
      GM-CSF release seen in anti-IL-10-treated cells was not due to functional
      antagonism as rolipram, PGE2 and 8-Br-cyclic AMP were equi-effective at all
      concentrations of LPS studied. 5. These data indicate that cyclic AMP-elevating
      drugs attenuate the elaboration of GM-CSF from LPS-stimulated human monocytes by
      a mechanism that is not mediated via IL-10. Suppression of GM-CSF from monocytes
      may explain, at least in part, the efficacy of PDE4 inhibitors in clinical trials
      of chronic obstructive pulmonary disease.

PMID- 11522598
TI  - Adenosine A2A receptor antagonists are potential antidepressants: evidence based
      on pharmacology and A2A receptor knockout mice.
AB  - 1. Adenosine, an ubiquitous neuromodulator, and its analogues have been shown to
      produce 'depressant' effects in animal models believed to be relevant to
      depressive disorders, while adenosine receptor antagonists have been found to
      reverse adenosine-mediated 'depressant' effect. 2. We have designed studies to
      assess whether adenosine A2A receptor antagonists, or genetic inactivation of the
      receptor would be effective in established screening procedures, such as tail
      suspension and forced swim tests, which are predictive of clinical antidepressant
      activity. 3. Adenosine A2A receptor knockout mice were found to be less sensitive
      to 'depressant' challenges than their wildtype littermates. Consistently, the
      adenosine A2A receptor blockers SCH 58261 (1 - 10 mg kg(-1), i.p.) and KW 6002
      (0.1 - 10 mg kg(-1), p.o.) reduced the total immobility time in the tail
      suspension test. 4. The efficacy of adenosine A2A receptor antagonists in
      reducing immobility time in the tail suspension test was confirmed and extended
      in two groups of mice. Specifically, SCH 58261 (1 - 10 mg kg(-1)) and ZM 241385
      (15 - 60 mg kg(-1)) were effective in mice previously screened for having high
      immobility time, while SCH 58261 at 10 mg kg(-1) reduced immobility of mice that
      were selectively bred for their spontaneous 'helplessness' in this assay. 5.
      Additional experiments were carried out using the forced swim test. SCH 58261 at
      10 mg kg(-1) reduced the immobility time by 61%, while KW 6002 decreased the
      total immobility time at the doses of 1 and 10 mg kg(-1) by 75 and 79%,
      respectively. 6. Administration of the dopamine D2 receptor antagonist
      haloperidol (50 - 200 microg kg(-1) i.p.) prevented the antidepressant-like
      effects elicited by SCH 58261 (10 mg kg(-1) i.p.) in forced swim test whereas it
      left unaltered its stimulant motor effects. 7. In conclusion, these data support
      the hypothesis that A2A receptor antagonists prolong escape-directed behaviour in
      two screening tests for antidepressants. Altogether the results support the
      hypothesis that blockade of the adenosine A2A receptor might be an interesting
      target for the development of effective antidepressant agents.

PMID- 11522599
TI  - Dependency of detrusor contractions on calcium sensitization and calcium entry
      through LOE-908-sensitive channels.
AB  - 1. The subcellular mechanisms regulating stimulus-contraction coupling in
      detrusor remain to be determined. We used Ca(2+)-free solutions, Ca(2+) channel
      blockers, cyclopiazonic acid (CPA), and RhoA kinase (ROK) inhibitors to test the
      hypothesis that Ca(2+) influx and Ca(2+) sensitization play primary roles. 2. In
      rabbit detrusor, peak bethanechol (BE)-induced force was inhibited 90% by
      incubation for 3 min in a Ca(2+)-free solution. By comparison, a 20 min
      incubation of rabbit femoral artery in a Ca(2+)-free solution reduced receptor
      induced force by only 5%. 3. In detrusor, inhibition of sarcoplasmic reticular
      (SR) Ca(2+) release by 2APB, or depletion of SR Ca(2+) by CPA, inhibited BE
      induced force by only 27%. The CPA-insensitive force was abolished by LaCl3. By
      comparison, 2APB inhibited receptor-induced force in rabbit femoral artery by
      71%. 4. In the presence of the non-selective cation channel (NSCC) inhibitor, LOE
      908, BE did not produce an increase in [Ca(2+)]i but did produce weak increases
      in myosin phosphorylation and force. 5. Inhibitors of ROK-induced Ca(2+)
      sensitization, HA-1077 and Y-27632, inhibited BE-induced force by approximately
      50%, and in combination with LOE-908, nearly abolished force. 6. These data
      suggest that two principal muscarinic receptor-stimulated detrusor contractile
      mechanisms include NSCC activation, that elevates [Ca(2+)]i and ROK activation,
      that sensitizes cross bridges to Ca(2+).

PMID- 11522600
TI  - Real-time analysis of dopamine: antagonist interactions at recombinant human
      D2long receptor upon modulation of its activation state.
AB  - 1. Antipsychotic drugs may mediate their therapeutic effects not only by
      preventing the binding of dopamine but also by decreasing the propensity of the
      dopamine receptor to assume an active R* state. Ligand-mediated activation and
      blockade of the recombinant human D(2long) receptor was investigated in CHO-K1
      cells upon modulation of its R* state. 2. Both the Ala(371)Lys (A371K) and
      Thr(372)Arg (T372R) D2long receptor mutants could be activated in a ligand
      dependent manner via a chimeric G(alphaq/o) protein, and more efficaciously so
      than with the promiscuous G(alpha15) protein. 3. Dopamine and partial agonists
      (E(max): lisuride >> (+)-UH 232 approximately bromerguride) displayed dissimilar
      Ca(2+) kinetic properties at wild-type and mutant receptors. A371K and T372R
      D2long receptor mutants demonstrated an attenuated and enhanced maximal response
      to these partial agonists, respectively. 4. Dopamine antagonists were unable to
      block the transient high-magnitude Ca(2+) phase at the wild-type D2long receptor
      upon simultaneous exposure to antagonist and dopamine, while full blockade of the
      low-magnitude Ca(2+) phase did occur at a later time (onset-time: haloperidol <
      bromerguride < (+)-butaclamol). A similar, though more efficacious, antagonist
      profile was also found at the A371K mutant receptor. Conversely, the blockade of
      the low-magnitude Ca(2+) phase was attenuated (haloperidol) or almost absent [(+)
      butaclamol and bromerguride] at the T372R mutant receptor. 5. In conclusion,
      mutagenesis of the Ala(371) and Thr(372) positions affects in an opposite way the
      ligand-dependent activation and blockade of the D2long receptor. The observed
      attenuation of dopamine-mediated Ca(2+) signal generation with different decay
      times may underlie distinct properties of the dopaminergic ligands.

PMID- 11522601
TI  - Analysis of GABA(A)- and GABA(B)-receptor mediated effects on intracellular
      Ca(2+) in DRG hybrid neurones.
AB  - 1. Using pharmacological analysis and fura-2 spectrofluorimetry, we examined the
      effects of gamma-aminobutyric acid (GABA) and related substances on intracellular
      Ca(2+) concentration ([Ca(2+)]i) of hybrid neurones, called MD3 cells. The cell
      line was produced by fusion between a mouse neuroblastoma cell and a mouse dorsal
      root ganglion (DRG) neurone. 2. MD3 cells exhibited DRG neurone-like properties,
      such as immunoreactivity to microtubule-associated protein-2 and neurofilament
      proteins. Bath applications of capsaicin and alpha, beta-methylene adenosine
      triphosphate reversibly increased [Ca(2+)]i. However, repeated applications of
      capsaicin were much less effective. 3. Pressure applications of GABA (100
      microM), (Z)-3-[(aminoiminomethyl) thio] prop-2-enoic acid sulphate (ZAPA; 100
      microM), an agonist at low affinity GABA(A)-receptors, or KCl (25 mM),
      transiently increased [Ca(2+)]i. 4. Bath application of bicuculline (100 nM - 100
      microM), but not picrotoxinin (10 - 25 microM), antagonized GABA-induced
      increases in [Ca(2+)]i in a concentration-dependent manner (IC(50)=9.3 microM).
      5. Ca(2+)-free perfusion reversibly abolished GABA-evoked increases in [Ca(2+)]i.
      Nifedipine and nimodipine eliminated GABA-evoked increases in [Ca(2+)]i. These
      results imply GABA response dependence on extracellular Ca(2+). 6. Baclofen (500
      nM - 100 microM) activation of GABA(B)-receptors reversibly attenuated KCl
      induced increases in [Ca(2+)]i in a concentration-dependent manner (EC(50)=1.8
      microM). 2-hydroxy-saclofen (1 - 20 microM) antagonized the baclofen-depression
      of the KCl-induced increase in [Ca(2+)]i. 7. In conclusion, GABA(A)-receptor
      activation had effects similar to depolarization by high external K(+),
      initiating Ca(2+) influx through high voltage-activated channels, thereby
      transiently elevating [Ca(2+)]i. GABA(B)-receptor activation reduced Ca(2+)
      influx evoked by depolarization, possibly at Ca(2+)-channel sites in MD3 cells.

PMID- 11522602
TI  - The plasma protein extravasation induced by adenosine and its analogues in the
      rat dorsal skin: evidence for the involvement of capsaicin sensitive primary
      afferent neurones and mast cells.
AB  - 1. The contribution of sensory neurons and mast cells to the oedema evoked by
      adenosine A1 (N(6)-cyclopentyladenosine, CPA, 3 - 30 nmol site(-1)), A2 (5'N
      ethylcarboxamidoadenosine, NECA, 1 - 10 nmol site(-1)) and A3 receptor agonists
      (N6-[3-iodobenzyl]-N-methyl-5'-carboxiamidoadenosine, IB-MECA, 0.01 - 3 nmol
      site(-1)) was investigated in the rat skin microvasculature, by the extravascular
      accumulation of intravenously-injected (i.v.) 125I-albumin. 2. Intradermal (i.d.)
      injection of adenosine and analogues induced increased microvascular permeability
      in a dose-dependent manner (IB-MECA > NECA > CPA > adenosine). The non-selective
      adenosine receptor antagonist theophylline (5 - 50 nmol site(-1)) markedly
      inhibited adenosine, CPA or NECA but not IB-MECA-induced plasma extravasation.
      The A1 receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, 0.3 - 3
      micromol kg(-1), i.v.) significantly reduced CPA-induced plasma extravasation
      whereas responses to adenosine, NECA or IB-MECA were unchanged. The A2 receptor
      antagonist 3,7-dymethyl-1-proprargylxanthine (DMPX, 0.5 - 50 nmol site(-1))
      significantly reduced NECA-induced plasma extravasation without affecting
      responses to adenosine, CPA and IB-MECA. 3. The tachykinin NK1 receptor
      antagonist (S)-1-[2-[3-(3,4-dichlorphenyl)-1 (3-isopropoxyphenylacetyl) piperidin
      3-yl] ethyl]-4-phenyl-1 azaniabicyclo [2.2.2]octane chloride (SR140333), but not
      the NK2 receptor antagonist (S)-N-methyl-N[4-acetylamino-4-phenyl piperidino)-2
      (3,4-dichlorophenyl)butyl]-benzamide (SR48968), significantly inhibited the
      plasma extravasation evoked by higher doses of adenosine (100 nmol site(-1)), CPA
      (100 nmol site(-1)), NECA (1 nmol site(-1)) and IB-MECA (0.1 - 1 nmol site(-1)).
      In rats treated with capsaicin to destroy sensory neurons, the response to higher
      doses of adenosine, CPA and NECA, but not IB-MECA, was significantly inhibited.
      4. The effects of adenosine and analogues were largely inhibited by histamine and
      5-hydroxytryptamine (5-HT) antagonists and by compound 48/80 pretreatment. 5. In
      conclusion, our results provide evidence that adenosine A1 and A2, but not A3,
      receptor agonists may function as cutaneous neurogenic pro-inflammatory
      mediators; acting via microvascular permeability-increasing mechanisms that can,
      depending on dose of agonist and purine receptor under study, involve the
      tachykinin NK1 receptor and mast cell amines.

PMID- 11522603
TI  - Pharmacological and biochemical characterization of A3 adenosine receptors in
      Jurkat T cells.
AB  - 1. The present work was devoted to the study of A3 adenosine receptors in Jurkat
      cells, a human leukemia line. 2. The A3 subtype was found by means of RT-PCR
      experiments and characterized by using the new A3 adenosine receptor antagonist
      [3H]-MRE 3008F20, the only A3 selective radioligand currently available.
      Saturation experiments revealed a single high affinity binding site with K(D) of
      1.9+/-0.2 nM and B(max) of 1.3+/-0.1 pmol mg(-1) of protein. 3. The
      pharmacological profile of [3H]-MRE 3008F20 binding on Jurkat cells was
      established using typical adenosine ligands which displayed a rank order of
      potency typical of the A3 subtype. 4. Thermodynamic data indicated that [3H]-MRE
      3008F20 binding to A3 subtype in Jurkat cells was entropy- and enthalpy-driven,
      according with that found in cells expressing the recombinant human A3 subtype.
      5. In functional assays the high affinity A3 agonists Cl-IB-MECA and IB-MECA were
      able to inhibit cyclic AMP accumulation and stimulate Ca(2+) release from
      intracellular Ca(2+) pools followed by Ca(2+) influx. 6. The presence of the
      other adenosine subtypes was investigated in Jurkat cells. A1 receptors were
      characterized using [3H]-DPCPX binding with a K(D) of 0.9+/-0.1 nM and B(max) of
      42+/-3 fmol mg(-1) of protein. A2A receptors were studied with [3H]-SCH 58261
      binding and revealed a K(D) of 2.5+/-0.3 nM and a B(max) of 1.4+/-0.2 pmol mg(-1)
      of protein. 7. In conclusion, by means of the first antagonist radioligand [3H]
      MRE 3008F20 we could demonstrate the existence of functional A3 receptors on
      Jurkat cells.

PMID- 11522604
TI  - Dibutyryl-cyclic GMP induces peripheral antinociception via activation of ATP
      sensitive K(+) channels in the rat PGE2-induced hyperalgesic paw.
AB  - 1. Using the rat paw pressure test, in which increased sensitivity is induced by
      intraplantar injection of prostaglandin E2, we studied the action of several K(+)
      channel blockers in order to determine what types of K(+) channels could be
      involved in the peripheral antinociception induced by dibutyrylguanosine 3 : 5'
      cyclic monophosphate (DbcGMP), a membrane permeable analogue of cyclic GMP. 2.
      DbcGMP elicited a dose-dependent (50, 75, 100 and 200 microg paw(-1)) peripheral
      antinociceptive effect. The effect of the 100 microg dose of DbcGMP was
      considered to be local since only a higher dose (300 microg paw(-1)) produced
      antinociception in the contralateral paw. 3. The antinociceptive effect of DbcGMP
      (100 microg paw(-1)) was dose-dependently antagonized by intraplantar
      administration of the sulphonylureas tolbutamide (20, 40 and 160 microg) and
      glibenclamide (40, 80 and 160 microg), selective blockers of ATP-sensitive K(+)
      channels. 4. Charybdotoxin (2 microg paw(-1)), a selective blocker of high
      conductance Ca(2+)-activated K(+) channels, and apamin (10 microg paw(-1)), a
      selective blocker of low conductance Ca(2+)-activated K(+) channels, did not
      modify the peripheral antinociception induced by DbcGMP. 5. Tetraethylammonium (2
      mg paw(-1)), 4-aminopyridine (200 microg paw(-1)) and cesium (800 paw(-1)), non
      selective voltage-gated potassium channel blockers, also had no effect. 6. Based
      on this experimental evidence, we conclude that the activation of ATP-sensitive
      K(+) channels could be the mechanism by which DbcGMP induces peripheral
      antinociception, and that Ca(2+)-activated K(+) channels and voltage-dependent
      K(+) channels appear not to be involved in the process.

PMID- 11522606
TI  - [125I-His(9)]-ghrelin, a novel radioligand for localizing GHS orphan receptors in
      human and rat tissue: up-regulation of receptors with athersclerosis.
AB  - 1. Ghrelin is the recently identified endogenous ligand for the cloned growth
      hormone secretagogue receptor (GHS-R). We have characterized for the first time
      the binding of human [125I-His(9)]-ghrelin to normal human and rat tissue and
      demonstrated expression of this 'orphan' receptor that has previously been
      predicted to exist from mRNA. Furthermore, we have discovered that [125I-His(9)]
      ghrelin density is significantly increased in atherosclerosis. 2. [125I-His(9)]
      Ghrelin bound to non-diseased human heart (left ventricle) with an association
      rate constant (k(obs)) of 0.16+/-0.004 min(-1), a dissociation rate constant of
      0.068+/-0.0005 min(-1) (kinetically derived K(D) of 0.1 nM; n=5 individuals+/
      s.e.mean), a K(D) of 0.43+/-0.08 nM and B(max) of 7.8+/-0.9 fmol mg(-1) protein
      (n=6 individual+/-s.e.mean). 3. Specific [125I-His(9)]-ghrelin binding was to the
      human vasculature including aorta, coronary, pulmonary, arcuate arteries in the
      kidney and saphenous veins. In rat tissues, binding sites were also localized to
      the vasculature in peripheral tissues as well as the granular layer of the
      cerebellum in the CNS. 4. [125I-His(9)]-Ghrelin binding was significantly up
      regulated (3 - 4 fold) in both atherosclerotic coronary arteries and saphenous
      vein grafts with advanced intimal thickening, compared with normal vessels
      (P<0.05). 5. Our results suggest that the native receptor for [125I-His(9)]
      ghrelin may be widely distributed in the human cardiovascular system.
      Furthermore, changes in the density of this proposed ghrelin receptor implicates
      this new transmitter system in the development of atherosclerosis and may
      therefore represent a novel therapeutic target in the treatment of cardiovascular
      disease.

PMID- 11522605
TI  - Pharmacological characterization of adenosine receptors in PGT-beta mouse pineal
      gland tumour cells.
AB  - 1. The adenosine receptor in mouse pinealocytes was identified and characterized
      using pharmacological and physiological approaches. 2. Expression of the two
      adenosine receptor subtypes A2B and A3 was detected in mouse pineal glands and
      PGT-beta cells by polymerase chain reaction and nucleotide sequencing. 3.
      Adenosine and 5'-N-ethylcarboxamidoadenosine (NECA) evoked cyclic AMP generation
      but the A2)-selective agonist 2-(4-(2-carboxyethyl)phenylethylamino)adenosine-5'
      N-ethylcarboxamideadenosine (CGS 21680) and the A1-specific agonists R-N(6)-(2
      phenylisopropyl)adenosine (R-PIA) and N(6)-cyclopentyladenosine (CPA) had little
      effect on intracellular cyclic AMP levels. The A2B receptor selective antagonists
      alloxazine and enprofylline completely blocked NECA-mediated cyclic AMP
      accumulation. 4. Treatment of cells with the A3-selective agonist N(6)-(3
      iodobenzyl)-5'-(N-methylcarbamoyl)adenosine (IB-MECA) inhibited the elevation of
      the cyclic AMP level induced by NECA or isoproterenol in a concentration
      dependent manner with maximal inhibition of 40 - 50%. These responses were
      blocked by the specific A3 adenosine receptor antagonist MRS 1191. Pretreatment
      of the cells with pertussis toxin attenuated the IB-MECA-induced responses,
      suggesting that this effect occurred via the pertussis toxin-sensitive inhibitory
      G proteins. 5. IB-MECA also caused a concentration-dependent elevation in
      [Ca(2+)]i and IP3 content. Both the responses induced by IB-MECA were attenuated
      by treatment with U73122 or phorbol 12-myristate 13-acetate. 6. These data
      suggest the presence of both A2B and A3 adenosine receptors in mouse pineal
      tumour cells and that the A2B receptor is positively coupled to adenylyl cyclase
      whereas the A3 receptor is negatively coupled to adenylyl cyclase and also
      coupled to phospholipase C.

PMID- 11522607
TI  - Effects of ACE inhibition and angiotensin II type 1 receptor blockade on cardiac
      function and G proteins in rats with chronic heart failure.
AB  - 1. Inhibition of the renin-angiotensin system (RAS) improves symptoms and
      prognosis in heart failure. The experimental basis for these benefits remains
      unclear. We examined the effects of inhibition of ACE or blockade of angiotensin
      II type 1 (AT1) receptor on the haemodynamics, cardiac G-proteins, and collagen
      synthesis of rats with coronary artery ligation (CAL), a model in which chronic
      heart failure (CHF) is induced. 2. Rats were orally treated with the ACE
      inhibitor trandolapril (3 mg kg(-1) day(-1)) or the AT1 receptor blocker L-158809
      (1 mg kg(-1) day(-1)) from the 2nd to 8th week after CAL. CAL resulted in
      decreases in the left ventricular systolic pressure and its positive and negative
      dP/dt, an increase in the left ventricular end-diastolic pressure, and the
      rightward shift of the left ventricular pressure-volume curve. Long-term
      treatment with either drug improved these signs of CHF to a similar degree. 3.
      Cardiac Gsalpha and Gqalpha protein levels decreased, whereas the level of
      Gialpha protein increased in the animals with CHF. Long-term treatment with
      trandolapril or L-158809 attenuated the increase in the level of cardiac Gialpha
      protein of the animals with CHF without affecting Gsalpha and Gqalpha protein
      levels. Cardiac collagen content of the failing heart increased, whose increase
      was blocked by treatment with either drug. 4. Exogenous angiotensin I stimulated
      collagen synthesis in cultured cardiac fibroblasts, whose stimulation was
      attenuated by either drug. 5. These results suggest that blockade of the RAS, at
      either the receptor level or the synthetic enzyme level, may attenuate the
      cardiac fibrosis that occurs after CAL and thus affect the remodelling of the
      failing heart.

PMID- 11522608
TI  - Differential effects of anandamide on acetylcholine release in the guinea-pig
      ileum mediated via vanilloid and non-CB1 cannabinoid receptors.
AB  - 1. The effects of anandamide on [3H]-acetylcholine release and muscle contraction
      were studied on the myenteric plexus-longitudinal muscle preparation of the
      guinea-pig ileum preincubated with [3H]-choline. 2. Anandamide increased both
      basal [3H]-acetylcholine release (pEC(50) 6.3) and muscle tone (pEC(50) 6.3). The
      concentration-response curves for anandamide were shifted to the right by 1
      microM capsazepine (pK(B) 7.5 and 7.6), and by the combined blockade of NK1 and
      NK3 tachykinin receptors with the antagonists CP99994 plus SR142801 (each 0.1
      microM). The CB1 and CB2 receptor antagonists, SR141716A (1 microM) and SR144528
      (30 nM), did not modify the facilitatory effects of anandamide. 3. Anandamide
      inhibited the electrically-evoked release of [3H]-acetylcholine (pEC(50) 5.8) and
      contractions (pEC(50) 5.2). The contractile response to the muscarinic agonist
      methacholine was not significantly affected by 10 microM anandamide. 4. The
      inhibitory effects of anandamide were not changed by either capsazepine (1
      microM), SR144528 (30 nM) or CP99994 plus SR142801 (each 0.1 microM). SR141716A
      (1 microM) produced rightward shifts in the inhibitory concentration-response
      curves for anandamide yielding pK(B) values of 6.6 and 6.2. 5. CP55940 inhibited
      the evoked [3H]-acetylcholine release and contractions, and SR141716A (0.1
      microM) shifted the concentration-response curves of CP55940 to the right with
      pK(B) values of 8.4 and 8.9. 6. The experiments confirm the existence of release
      inhibitory CB1 receptors on cholinergic myenteric neurones. We conclude that
      anandamide inhibits the evoked acetylcholine release via stimulation of a
      receptor that is different from the CB1 and CB2 receptor. Furthermore, anandamide
      increases basal acetylcholine release via stimulation of vanilloid receptors
      located at primary afferent fibres.

PMID- 11522609
TI  - Inhibitory effects of brefeldin A, a membrane transport blocker, on the
      bradykinin-induced hyperpolarization-mediated relaxation in the porcine coronary
      artery.
AB  - 1. To elucidate the mechanism of the relaxation mediated by endothelium-derived
      hyperpolarizing factors (EDHFs), the effect of brefeldin A, a membrane transport
      blocker, on cytosolic Ca(2+) concentration ([Ca(2+)]i) and tension was determined
      in the porcine coronary arterial strips. We also examined the effect of brefeldin
      A on [Ca(2+)]i in the endothelial cells of the porcine aortic valve. 2. In the
      presence of 10 microM indomethacin and 30 microM N(G)-nitro-L-arginine (L-NOARG),
      both bradykinin and substance P induced a transient decrease in [Ca(2+)]i and
      tension in arterial strips contracted with 100 nM U46619 (thromboxane A2
      analogue). A 6 h pre-treatment with 20 microg ml(-1) brefeldin A abolished the
      bradykinin-induced relaxation, while it had no effect on the substance P-induced
      relaxation. 3. In the absence of indomethacin and L-NOARG, brefeldin A had no
      effect on the bradykinin-induced relaxation during the contraction induced by
      U46619 or 118 mM K(+). 4. The indomethacin/L-NOARG-resistant relaxation induced
      by bradykinin was completely inhibited by 3 mM tetrabutylammonium (non-specific
      Ca(2+)-activated K(+) channel blocker), while that induced by substance P was not
      inhibited by 3 mM tetrabutylammonium or 1 mM 4-aminopyridine (voltage-dependent
      K(+) channels blocker) alone, but completely inhibited by their combination. 5.
      Brefeldin A had no effect on the [Ca(2+)]i elevation in endothelial cells induced
      by bradykinin or substance P. 6. In conclusion, bradykinin produce EDHF in a
      brefeldin A-sensitive mechanism in the porcine coronary artery. However, this
      mechanism is not active in a substance P-induced production of EDHF, which thus
      suggests EDHF to be more than a single entity.

PMID- 11522610
TI  - Noradrenaline-induced changes in intracellular Ca(2+) and tension in mesenteric
      arteries from diabetic rats.
AB  - 1. The purpose of this investigation was to determine whether enhanced
      contractile responses to noradrenaline (NA) of mesenteric arteries from rats with
      chronic streptozotocin-induced diabetes are associated with increases in mean
      cytosolic [Ca(2+)]i. 2. [Ca(2+)]i was measured with fura 2-AM, and was monitored
      simultaneously with tension in perfused endothelium-denuded mesenteric arterial
      rings from 12 - 14 week diabetic rats and age- and gender-matched control rats.
      3. Basal [Ca(2+)]i (expressed as R(n), the normalized fura 2 ratio) was not
      significantly different in arteries from control and diabetic rats. Similarly, no
      differences between control and diabetic arteries in the tension or [Ca(2+)]i
      responses to 80 mM KCl in the presence of phentolamine were detected. 4. The rate
      of tension development, peak tension and integrated tension in response to 30
      microM NA were all significantly greater in diabetic than control arteries.
      However, this was not associated with enhancement of the corresponding [Ca(2+)]i
      responses in the diabetic arteries. 5. Peak contractile responses to perfusion
      with both 0.3 and 3 microM NA, but peak [Ca(2+)]i only in response to 0.3 microM
      NA, were significantly greater in diabetic than control arteries. 6. NA (30
      microM) produced a greater increase in both peak tension and [Ca(2+)]i in
      diabetic than control arteries perfused with Ca(2+)-free solution containing 1 mM
      EGTA. Neither the rate nor the magnitude of NA-induced Ca(2+) influx appeared to
      be altered in the diabetic arteries. 7. The enhanced sustained contractile
      response of diabetic arteries to NA appears to be dissociated from increases in
      [Ca(2+)]i, and may be due to other factors, such as an increase in the Ca(2+)
      sensitivity of the contractile proteins.

PMID- 11522611
TI  - Mechanism of action of angiotensin II in human isolated subcutaneous resistance
      arteries.
AB  - 1. Human isolated subcutaneous arteries were mounted in a myograph and isometric
      tension measured. In some experiments, intracellular calcium [Ca(2+)]i was also
      measured using fura-2. 2. Angiotensin II (100 pM - 1 microM) increased [Ca(2+)]i
      and tone in a concentration-dependent manner. The effects of angiotensin II (100
      nM) were inhibited by an AT1-receptor antagonist, candesartan (100 pM). 3.
      Ryanodine (10 microM), had no effect on angiotensin II-induced responses, but
      removal of extracellular Ca(2+) abolished angiotensin II-induced rise in
      [Ca(2+)]i and tone. Inhibition of Ca(2+) entry by Ni(2+) (2 mM), also inhibited
      angiotensin II responses. The dihydropyridine, L-type calcium channel antagonist,
      amlodipine (10 microM), only partially attenuated angiotensin II responses. 4.
      Inhibition of protein kinase C (PKC) by chelerythrine (1 microM), or by overnight
      exposure to a phorbol ester (PDBu; 500 nM) had no effect on angiotensin II
      induced contraction. 5. Genistein (10 microM), a tyrosine kinase inhibitor,
      inhibited angiotensin II-induced contraction, but did not inhibit the rise in
      [Ca(2+)]i, suggesting that at this concentration it affected the calcium
      sensitivity of the contractile apparatus. Genistein did not affect responses to
      norepinephrine (NE) or high potassium (KPSS). 6. A selective MEK inhibitor,
      PD98059 (30 microM), inhibited both the angiotensin II-induced contraction and
      rise in [Ca(2+)]i, but had no effect on responses to NE or KPSS. 7. AT1
      activation causes Ca(2+) influx via L-type calcium channels and a dihydropyridine
      insensitive route, but does not release Ca(2+) from intracellular sites.
      Activation of tyrosine kinase(s) and the ERK 1/2 pathway, but not classical or
      novel PKC, also play a role in angiotensin II-induced contraction in human
      subcutaneous resistance arteries.

PMID- 11522612
TI  - VEGF stimulation of endothelial cell PAF synthesis is mediated by group V 14 kDa
      secretory phospholipase A2.
AB  - 1. Vascular endothelial growth factor (VEGF) is a potent inducer of inflammation,
      and we have shown that this latter effect is mediated through endothelial cell
      (EC) PAF synthesis. Since the phospholipid remodelling pathway enzymes (CoA
      independent transacylase, CoA-IT; phospholipase A2, PLA2; and lyso-PAF
      acetyltransferase, lyso-PAF-AT) may participate in PAF synthesis, we assessed
      their contribution to VEGF-induced PAF synthesis in bovine aortic EC (BAEC) and
      human umbilical vein EC (HUVEC). 2. VEGF enhanced BAEC and HUVEC PAF synthesis by
      up to 28 and 4 fold above basal levels respectively. 3. A pretreatment with a CoA
      IT and lyso-PAF-AT inhibitor (Sanguinarin; 500 nM) blocked VEGF-induced PAF
      synthesis by 95%, a specific CoA-IT inhibitor (SKF45905; 10 - 50 microM) was
      without effect, confirming the crucial role of the PLA2 and lyso-PAF-AT. 4.
      Treatment with secreted PLA2 (sPLA2) inhibitors which have been shown to inhibit
      both groups IIA and V sPLA2 (SB203347; 10 microM and LY311727; 100 microM)
      blocked EC PAF synthesis by up to 90%, whereas selective inhibition of group IIA
      sPLA2 (LY311727; 1 microM) had no significant effect. 5. RT - PCR and Western
      blot analyses demonstrated the presence of group V sPLA2 whereas group IIA sPLA2
      was undetected in EC. 6. Treatment with cytosolic and calcium-independent PLA2
      inhibitors (Arachidonyl trifluoromethyl ketone, Bromoenol lactone, Methyl
      arachydonyl fluorophosphate, up to 50 microM) did not prevent but rather
      potentiated the VEGF effect on EC PAF synthesis. 7. These results provide
      evidence that with VEGF activation of EC cells, the group V sPLA2 provides
      substrate for EC PAF formation.

PMID- 11522613
TI  - NO-induced relaxation of labouring and non-labouring human myometrium is not
      mediated by cyclic GMP.
AB  - 1. In myometrial strips from near-term non-labouring human uterus, addition of
      oxytocin (OT) evoked dose-dependent (10 - 3000 nM) phasic contractions that were
      antagonized by atosiban (1 microM) and relaxed by addition of the nitric oxide
      donor S-nitroso L-cysteine (Cys-NO). In near-term labouring myometrium, however,
      addition of OT was ineffective at raising additional tone. 2. In both labouring
      and non-labouring tissue, Cys-NO mediated relaxation of spontaneous or OT-induced
      contractions (IC(50)=1 microM) was unaffected by prior addition of the guanylyl
      cyclase (GC) inhibitors ODQ (1H-[1,2,4]oxadiazolo[4,3,-alpha]quinoxalin-1-one; 1
      microM), or methylene blue (MB; 10 microM). 3. Elevation of intracellular cyclic
      GMP accompanying 30 microM Cys-NO addition in non-labouring tissue (7.5 fold) or
      in labouring tissues (2.5 fold) was completely blocked in tissues that had been
      pre-treated with ODQ or MB. 4. Charybdotoxin (ChTx), iberiotoxin (IbTx) and
      kaliotoxin (KalTx) all shifted the Cys-NO inhibition curve to the right and
      reduced the degree of relaxation produced by maximal Cys-NO treatment (100 microM
      in non-labouring tissue; in labouring tissue, KalTx prevented Cys-NO mediated
      relaxation in both stimulated and unstimulated tissue. 5. Addition of the NO
      donor S-nitroso N-acetyl penicillamine (SNAP) produced a dose-dependent
      relaxation of pregnant myometrium while 3-morpholinosyndonimine (SIN-1) did not.
      The failure of SIN-1 to relax OT-induced contractions was not due to a failure of
      the donor to stimulate myometrial GC. 6. We demonstrate that despite the ability
      of NO to stimulate myometrial GC in pregnant uterine muscle, relaxations are
      independent of cyclic GMP action. Effects of K(+)-channel inhibitors suggests
      that NO-induced relaxation in human uterine smooth muscle may be subserved by
      direct or indirect activation of one or more calcium-activated K(+)-channels.

PMID- 11522614
TI  - A novel tachykinin NK2 receptor antagonist prevents motility-stimulating effects
      of neurokinin A in small intestine.
AB  - 1. MEN 11420 (nepadutant) is a potent, selective and competitive antagonist of
      tachykinin NK2 receptors. 2. The objective of the present study was to assess the
      capability of the drug to antagonize the stimulatory effects of neurokinin A
      (NKA) on gastrointestinal motility, as well as to change the fasting migrating
      motor complex (MMC). 3. Thirty-four male volunteers were randomized to treatment
      with either placebo or MEN 11420 in a double-blinded manner. Effects of MEN 11420
      (8 mg intravenously) were evaluated as changes in phases I, II and III of MMC, as
      well as contraction frequency, amplitude and motility index during baseline
      conditions and during stimulation of motility using NKA (25 pmol kg(-1) min(-1)
      intravenously). 4. NKA preceded by placebo increased the fraction of time
      occupied by phase II, increased contraction frequency, amplitude and motility
      index. 5. MEN 11420 effectively antagonized the motility-stimulating effects of
      NKA. MEN 11420 reduced the phase II-stimulating effect of NKA. In addition, the
      stimulatory effect of NKA on contraction frequency and amplitude, as well as
      motility index were inhibited by MEN 11420. MEN 11420 did not affect the
      characteristics of MMC during saline infusion. 6. Plasma levels of MEN 11420
      peaked during the first hour after infusion and decreased to less than half
      during the first 2 h. 7. In conclusion, intravenous MEN 11420 effectively
      inhibited NKA-stimulated, but not basal gastrointestinal motility, and was well
      tolerated by all subjects.

PMID- 11522615
TI  - Influence of aldosterone on collagen synthesis and proliferation of rat cardiac
      fibroblasts.
AB  - 1. Previous in vivo studies in men and experimental animal models have shown that
      hyperaldosteronemia is correlated with cardiac fibrosis due to increased total
      collagen synthesis. As yet, it is unclear whether aldosterone has direct pro
      fibrogenic effect on cardiac fibroblasts, the fibrogenic effector cell in the
      myocardium, and if so which procollagens specifically are synthesized at higher
      rates. 2. The present study aims at establishing whether de novo collagen
      synthesis by cardiac fibroblasts is enhanced following exposure for 2x24 h to
      pharmacological (10(-7) - 10(-8) M), near-physiological (10(-9) M) or
      physiological (10(-10) - 10(-11) M) aldosterone concentrations. During the last
      24 h, cells were metabolically labelled with [35S]-methionine/[35S]-cysteine.
      Labelled procollagens were immunoprecipitated quantitatively using antibodies
      against specific procollagens. Contrary to expectations, 10(-7) M aldosterone
      inhibited significantly de novo synthesis of procollagens type I and IV (-35% and
      -42%, respectively). For procollagen type III, only a tendency towards inhibition
      was observed. At lower concentrations of aldosterone (10(-8) - 10(-10) M),
      synthesis of procollagens type I, III or IV was unaffected. 3. Cellular DNA
      synthesis under influence of aldosterone was evaluated by measuring BrdU
      incorporation. Cells were treated with aldosterone, while BrdU was added during
      the last 16 h of treatment. Aldosterone had no demonstrable effect on cellular
      proliferation. 4. Reverse transcription-polymerase chain reaction (RT - PCR)
      clearly demonstrated the presence of mineralocorticoid receptor mRNA in cardiac
      fibroblasts. 5. In spite of the expression of the mineralocorticoid receptor by
      cultured cardiac fibroblasts, the pro-fibrogenic effect of aldosterone as
      observed in vivo, is not likely to be due to a direct effect of this hormone in
      cardiac fibroblasts.

PMID- 11522616
TI  - Lipoxygenase modulation to reverse carcinogenesis.
AB  - New studies of the relationship between polyunsaturated fatty acid metabolismand
      carcinogenesis have led to novel molecular targets for cancer chemoprevention
      research. These targets include procarcinogenic lipoxygenases (LOXs), including 5
      , 8-, and 12-LOX, and anticarcinogenic LOXs, including 15-LOX-1 and possibly 15
      LOX-2. Recent studies indicate that 15-LOX-1 is down-regulated in colorectal
      cancer cells and that the ability of nonsteroidal anti-inflammatory drugs, a
      class of clinically active cancer chemopreventive agents, to induce apoptosis and
      growth inhibition in these cells was dependent on the induction of 15-LOX-1 and
      its metabolic product 13-S-hydroxyoctadecadienoic acid. Consistent with the
      colorectal studies, 15-LOX very recently has shown anticarcinogenic activity in
      esophageal and prostatic carcinogenesis. Inhibitors of other LOXs (e.g., 5-LOX)
      have preclinical anticarcinogenic activity and are being developed for clinical
      chemoprevention study. These and other LOX data led us to propose that the
      various LOX pathways exist in a dynamic balance that shifts during carcinogenesis
      toward 5-, 8-, and 12-LOX (and cyclooxygenase-2) and away from 15-LOX. A novel
      approach for cancer chemoprevention would involve LOX modulators, i.e., agents
      that can induce the anticarcinogenic and/or inhibit the procarcinogenic LOXs,
      thereby shifting the balance of LOX activities from procarcinogenic to
      anticarcinogenic metabolism of polyunsaturated fatty acids.

PMID- 11522617
TI  - Adeno-associated virus for cancer gene therapy.

PMID- 11522618
TI  - Cooperative interactions of laminin 5 gamma2 chain, matrix metalloproteinase-2,
      and membrane type-1-matrix/metalloproteinase are required for mimicry of
      embryonic vasculogenesis by aggressive melanoma.
AB  - Vasculogenic mimicry describes a process where aggressive tumor cells in three
      dimensional matrices mimic embryonic vasculogenesis by forming extracellular
      matrix (ECM)-rich, patterned tubular networks. Microarray gene chip analyses
      revealed significant increases in the expression of laminin 5 (Ln-5, gamma2
      chain) and matrix metalloproteinases (MMP)-1, -2, -9, and MT1-MMP (MMP-14) in
      aggressive compared with poorly aggressive melanoma cells. These components
      colocalized with developing patterned networks and antisense oligonucleotides to
      the Ln-5 gamma2 chain (but not sense oligonucleotides), and antibodies to MMP-2
      or MT1-MMP (but not MMP-9) inhibited the formation of these networks. Cultures
      which did not receive antibodies to either MMPs-2 or -14 contained the Ln-5
      gamma2 chain promigratory cleavage fragments. Poorly aggressive melanoma cells
      seeded on collagen I matrices preconditioned by the aggressive cells formed
      tubular networks along the Ln-5 gamma2 chain-enriched tracks deposited by the
      aggressive cells. These results suggest that increased expression of MMP-2 and
      MT1-MMP, along with matrix deposition of the Ln-5 gamma2 chain and/or its
      cleavage fragments, are required for vasculogenic mimicry by aggressive melanoma
      cells. Furthermore, the apparent recapitulation of laminin-rich, patterned
      networks observed in aggressive melanoma patients' tissue sections by aggressive
      melanoma tumor cells in three-dimensional culture may also serve as a model to
      help identify specific molecular targets which could function as templates for
      the coordinated migration of aggressive tumor cells and their proteolytic
      remodeling of the ECM and may have profound implications for the development of
      novel therapies directed at the ECM to alter tumor progression.

PMID- 11522619
TI  - Enhanced adenovirus transgene expression in malignant cells treated with the
      histone deacetylase inhibitor FR901228.
AB  - The presence of coxsackie and adenovirus receptor (CAR) and alpha(v) integrin on
      cell surfaces is required for efficient adenovirus infection. Treatment of cells
      with the histone deacetylase inhibitor FR901228 (depsipeptide) increased CAR and
      alpha(v) integrin RNA levels in six cancer cell lines. Sodium butyrate and
      trichostatin A, other histone deacetylase inhibitors, caused similar increases.
      Cells treated with FR901228 prior to infection had a 4-10-fold increase in
      transgene expression from a beta-galactosidase-expressing adenoviral vector.
      These studies suggest that FR901228 increases the efficiency of adenoviral
      transgene expression and may be useful in cancer gene therapy.

PMID- 11522620
TI  - Loss of annexin II heavy and light chains in prostate cancer and its precursors.
AB  - Annexin II mRNA coding for a calcium binding protein was found to be absent in
      prostate cancer by subtractive hybridization and Northern analysis. In contrast
      to high expression in normal and benign hyperplastic glandular and basal
      epithelium, Annexin II heavy (p36) and light (p11) chains in 31/31 prostate
      cancer specimens were lost immunohistochemically. In glands involved by prostate
      intraepithelial neoplasia, 65% lost both chains in glandular epithelial cells,
      whereas basal cells were all positively stained. Southern analysis of cancer DNA
      showed no noticeable deletion in p36 gene. LNCaP cells treated with 5-azacytidine
      re-expressed p36, suggesting methylation could be responsible for the silencing.

PMID- 11522621
TI  - Frequent alterations of the p14(ARF) and p16(INK4a) genes in primary central
      nervous system lymphomas.
AB  - To elucidate the role of p53/p16(INK4a)/RB1 pathways in the tumorigenesis of
      primary central nervous system lymphomas (PCNSLs), we have analyzed p14(ARF),
      p16(INK4a), RB1, p21(Waf1), and p27(Kip1) status in a series of their 18 sporadic
      cases of diffuse large B-cell lymphoma, using methylation-specific PCR,
      differential PCR, and immunohistochemistry. Homozygous deletion or methylation of
      p14(ARF) was detected in 10 (56%) PCNSLs, and they were almost entirely deletions
      (except 1 case). A total of 11 (61%) PCNSLs demonstrated homozygous deletion (6
      cases) or methylation (5 cases) of p16(INK4a). Six tumors showed both p14(ARF)
      and p16(INK4a) homozygous deletions. Hypermethylation of the RB1 and the
      p27(Kip1) promoter region was detected in 2 (11%) cases, whereas p21(Waf1)
      methylation was not detected in any. Immunohistochemistry revealed loss of
      p14(ARF) and p16(INK4a) expression in 10 (56%) samples, correlating with the gene
      status. Four cases showed independent negative immunoreactivity for pRB and
      p27(Kip1), and nearly one-half of cases (8 of 18; 44%) were characterized by lack
      of p21(Waf1) expression. These results indicate that inactivation of p14(ARF) and
      p16(INK4a) by either homozygous deletion or promoter hypermethylation represents
      an important molecular pathogenesis in PCNSLs. Hypermethylation of RB1,
      p21(Waf1), and p27(Kip1) appears to be of minor significance, these genes being
      independently methylated in PCNSLs.

PMID- 11522622
TI  - TSU-Pr1 and JCA-1 cells are derivatives of T24 bladder carcinoma cells and are
      not of prostatic origin.
AB  - We have shown previously that the putative prostate carcinoma cell lines TSU-Pr1
      and JCA-1 share a common origin. The observation that these cell lines have p53
      and Ha-ras mutations identical to those in bladder carcinoma cell line T24
      prompted us to investigate their possible interrelations. We used cytogenetics
      and DNA profiling to compare the genetic backgrounds of the three cell lines. At
      least 12 structural chromosomal abnormalities are shared between T24, TSU-Pr1,
      and JCA-1 cells. DNA profiles were identical for all three cell lines. These
      results clearly indicate that the cell lines TSU-Pr1 and JCA-1 are not of
      prostatic origin but are derivatives of the bladder carcinoma cell line T24. TSU
      Pr1 and, to a lesser extent, JCA-1 are frequently used as models in prostate
      cancer research, and numerous publications have appeared based on these lines.
      Several other T24 cross-contaminants have been identified in the past, and some
      of these, such as ECV304, continue to be used under the wrong identity. Our
      findings highlight the insidious problem that can occur when information
      regarding cross-contamination does not reach individual researchers and/or the
      importance of the problem is not fully acknowledged.

PMID- 11522623
TI  - Identification of AF17 as a downstream gene of the beta-catenin/T-cell factor
      pathway and its involvement in colorectal carcinogenesis.
AB  - To elucidate the molecular mechanism of colorectal carcinogenesis, we have been
      attempting to isolate genes involved in the beta-catenin/T-cell factor pathway.
      In the experiments reported here, analysis by cDNA microarray indicated that
      AF17, a fusion partner of the MLL gene in acute leukemias with t(11;17)(q23;q21),
      was transactivated according to accumulation of beta-catenin. Expression of AF17
      was significantly enhanced in 8 of the 12 colorectal cancer tissues examined.
      Introduction of a plasmid designed to express AF17 stimulated growth of NIH3T3
      cells, and fluorescence-activated cell sorter analysis indicated that the AF17
      regulation of cell-cycle progression was occurring mainly at the G(2)-M
      transition. Our results suggest that the AF17 gene product is likely to be
      involved in the beta-catenin-T-cell factor/lymphoid enhancer factor signaling
      pathway and to function as a growth-promoting, oncogenic protein. These findings
      should aid development of new strategies for diagnosis, treatment, and prevention
      of colon cancers and acute leukemias by clarifying the pathogenesis of these
      conditions.

PMID- 11522624
TI  - Mutability of p53 hotspot codons to benzo(a)pyrene diol epoxide (BPDE) and the
      frequency of p53 mutations in nontumorous human lung.
AB  - p53 mutations are common in lung cancer. In smoking-associated lung cancer,the
      occurrence of G:C to T:A transversions at hotspot codons, e.g., 157, 248, 249,and
      273, has been linked to the presence of carcinogenic chemicalsin tobacco smoke
      including polycyclic aromatic hydrocarbons suchas benzo(a)pyrene (BP). In the
      present study, we have used a highly sensitive mutation assay to determine the
      p53 mutation load in nontumorous human lung and to study the mutability of p53
      codons 157, 248, 249, and 250 to benzo(a)pyrene-diol-epoxide (BPDE), an active
      metabolite of BP in human bronchial epithelial BEAS-2B cells. We determined the
      p53 mutational load at codons 157, 248, 249, and 250 in nontumorous peripheral
      lung tissue either from lung cancer cases among smokers or noncancer controls
      among smokers and nonsmokers. A 5-25-fold higher frequency of GTC(val) to
      TTC(phe) transversions at codon 157 was found in nontumorous samples (57%) from
      cancer cases (n = 14) when compared with noncancer controls (n = 8; P < 0.01).
      Fifty percent (7/14) of the nontumorous samples from lung cancer cases showed a
      high frequency of codon 249 AGG(arg) to AGT(ser) mutations (P < 0.02). Four of
      these seven samples with AGT(ser) mutations also showed a high frequency of codon
      249 AGG(arg) to ATG(met) mutations, whereas only one sample showed a codon 250
      CCC to ACC transversion. Tumor tissue from these lung cancer cases (38%)
      contained p53 mutations but were different from the above mutations found in the
      nontumorous pair. Noncancer control samples from smokers or nonsmokers did not
      contain any detectable mutations at codons 248, 249, or 250. BEAS-2B bronchial
      epithelial cells exposed to doses of 0.125, 0.5, and 1.0 microM BPDE, showed G:C
      to T:A transversions at codon 157 at a frequency of 3.5 x 10(-7), 4.4 x 10(-7),
      and 8.9 x 10(-7), respectively. No mutations at codon 157 were found in the DMSO
      treated controls. These doses of BPDE induced higher frequencies, ranging from 4
      12-fold, of G:C to T:A transversions at codon 248, G:C to T:A transversions and
      G:C to A:T transitions at codon 249, and C:G to T:A transitions at codon 250 when
      compared with the DMSO-treated controls. These data are consistent with the
      hypothesis that chemical carcinogens such as BP in cigarette smoke cause G:C to
      T:A transversions at p53 codons 157, 248, and 249 and that nontumorous lung
      tissues from smokers with lung cancer carry a high p53 mutational load at these
      codons.

PMID- 11522625
TI  - Helicobacter pylori membrane protein 1: a new carcinogenic factor of Helicobacter
      pylori.
AB  - Considering a suspected link between Helicobacter pylori infection and human
      stomach cancer, a new H. pylori gene for membrane protein 1 (HP-MP1) was recently
      cloned. Because HP-MP1 induces release of inflammatory cytokines and tumor
      necrosis factor-alpha acts as both initiator and tumor promoter, we studied the
      possible involvement of HP-MP1 in carcinogenesis of H. pylori. Two cell lines,
      BALB/3T3 cells as control and v-Ha-ras-transfected BALB/3T3 cells (Bhas 42 cells)
      as putative initiated cells, were each transfected with HP-MP1, urease B genes,
      or vector alone. All of the Bhas/mpl clones showed strong expression of tumor
      necrosis factor-alpha gene and produced tumors in 100% of nude mice. Two Bhas/ure
      clones showed weak tumorigenicity; the other Bhas and BALB clones showed none.
      Results indicate strong carcinogenic activity of HP-MP1 in cooperation with viral
      Ras protein and weak activity of urease B.

PMID- 11522626
TI  - Estrogens do not modify MAP kinase-dependent nuclear signaling during stimulation
      of early G(1) progression in human breast cancer cells.
AB  - Estrogens are direct mitogens for hormone-responsive human breast cancercells,
      where they promote cell cycle progression and induce transcriptional activation
      of "immediate early" and cyclin genes. Nongenomic signaling by estrogens,
      including rapid changes of mitogen-activated protein(MAP) kinase and other signal
      transduction-cascades activity, has been proposed to be essential for the
      mitogenic actions of these hormones and their nuclear receptors. Because
      regulation of gene transcription is considered a key step in cell cycle control
      by mitogenic protein kinase cascades, here we investigated the possibility that
      estrogen might induce the activation of extracellular signal-regulated kinase
      (Erk) 1/2-, c-Jun NH(2)-terminal kinase-, p38- or protein kinase A-responsive
      transcription factors in the cell nucleus during stimulation of early G(1)
      progression, a timing coincident with the maximum effects of these hormones on
      such enzyme activity. No significant changes in protein kinase-mediated
      transcription factor activity could be detected here after estrogen stimulation
      of either MCF-7 or ZR-75.1 cells. Furthermore, these steroids were able to induce
      activation of the human CCND1 gene promoter, accumulation of cyclin D1 and pRb
      phosphorylation, all key events in cell cycle stimulation by mitogens, even in
      the presence of Erk1/2 activation blockade by a MAP kinase-activating kinase
      (Mek)1/2 inhibitor. Thus, estrogens do not appear to convey significant protein
      kinase-dependent signaling to the cell nucleus during the early phases of human
      breast cancer cell stimulation. Furthermore, hormonal regulation of G(1) gene
      transcription can occur even without additional activation of the Mek-Erk1/2
      pathway by estrogen receptors.

PMID- 11522627
TI  - Smoking increases carcinogenic polycyclic aromatic hydrocarbons in human lung
      tissue.
AB  - Tobacco smoke is a major source of human exposure to polycyclic aromatic
      hydrocarbons (PAHs). The concentration of PAHs in lung tissue would reflect an
      individual's dose, and its variation could perhaps reflect cancer risk. Eleven
      PAHs were measured in 70 lung tissue samples from cancer-free autopsy donors by
      gas chromatography-mass spectrometry. There were 37 smokers and 33 nonsmokers as
      estimated by serum cotinine concentration. The sum of PAH concentrations was
      higher in smokers (P = 0.01), and there was a dose-response relationship for
      greater smoking (P < 0.01). Smoking increased the concentration of five PAHs
      including benzo(a)pyrene, which increased approximately 2-fold. The risk for
      increasing carcinogenic PAHs (odds ratio, 8.20; 95% confidence interval, 2.39
      28.09) was 3-fold compared with noncarcinogenic PAHs (odds ratio, 2.61; 95%
      confidence interval, 0.75-9.12). A higher concentration of PAHs was detected in
      the lung tissue of males, although the estimated smoking was similar in males and
      females. Race was not associated with PAH concentrations overall, but PAH
      concentrations appeared to be higher in African-American males than in any other
      group. Age was weakly correlated with an increase in fluoranthene and pyrene. The
      measurement of PAHs in human lung tissue can be used to estimate the actual dose
      to the target organ.

PMID- 11522628
TI  - Therapeutic implications of enhanced G(0)/G(1) checkpoint control induced by
      coculture of prostate cancer cells with osteoblasts.
AB  - Osteoblastic metastases are common in lethal prostate cancer. Effective therapy
      for bone metastases is lacking. Thus, developing an appropriate in vitro
      screening system is critical to prioritize which of the newly developed agents
      should undergo additional expensive and time-consuming in vivo evaluation in bone
      metastases animal models. In the past, such in vitro screening evaluated the
      response of prostate cancer cells to chemotherapeutic agents in monoculture
      without the presence of osteoblasts. In such monoculture, prostate cancer cells
      have a high (i.e., >90%) proliferative growth fraction. In contrast, the growth
      fraction (i.e., mean: 7.1 +/- 0.8%; median: 3.1%) in 117 metastatic sites of
      prostate cancer obtained from 11 androgen ablation failing patients at "warm"
      autopsy was found to be >10-fold lower. To better mimic the lower growth fraction
      observed clinically, LNCaP human prostate cancer cells were cocultured with
      membrane-separated hFOB human osteoblasts. Such coculturing significantly lowered
      the growth fraction of the LNCaP cells (i.e., from >90 to <30%) without enhancing
      their low rate (i.e., <5%) of apoptosis. This lowering of the growth fraction was
      documented using flow cytometry, Ki-67 immunohistochemistry, and 5-bromo-2
      deoxyuridine incorporation. Using RNase protection assays, it was documented that
      coculture with osteoblasts causes enhanced p53, p27, and p21 expression leading
      to a decrease in the number of LNCaP cells entering the cell cycle (i.e.,
      enhanced number of LNCaP cells in G(0)-G(1) and a decrease in S and G(2)-M and
      thus the growth fraction). This osteoblast-induced enhanced G(0)-G(1) checkpoint
      control affected the chemosensitivity of LNCaP cells. This was documented by
      coculturing LNCaP cells with hFOB cells to condition the medium for 3 days to
      lower the growth fraction to <30% before exposing the LNCaP cells for 48 h to
      various concentrations of Taxol, doxorubicin, or thapsigargin (TG). In standard
      high (i.e., >90%) growth fraction cultures (i.e., cultures in the absence of
      osteoblast-conditioned medium), there was a dose-dependent and significant (P <
      0.05) increase in apoptosis of LNCaP cells exposed to Taxol or doxorubicin. In
      contrast, even the highest dose of Taxol (1 microM) did not enhance apoptosis of
      lower growth fraction LNCaP cells cultured in osteoblast-conditioned medium.
      Similarly, only the highest concentration of doxorubicin (1 microM) enhanced
      apoptosis in lower growth fraction cells. In contrast, 100 nM TG induced high
      levels of apoptosis in both lower and high-growth fraction LNCaP cultures. These
      results demonstrate that the osteoblast/LNCaP coculture system is a better in
      vitro screen than monoculture to identify proliferation-independent agents for
      the treatment of prostate cancer bone metastases, and TG is such an agent.

PMID- 11522629
TI  - Targeting oncolytic adenoviral agents to the epidermal growth factor pathway with
      a secretory fusion molecule.
AB  - Cancer gene therapy with conditionally replicating adenoviruses is a powerful way
      of overcoming low tumor transduction. However, one of the main remaining
      obstacles is the highly variable level of the coxsackie-adenovirus receptor
      expression on human primary cancers. In contrast, the epidermal growth factor
      receptor (EGFR) is overexpressed in various tumor types, and its expression
      correlates with metastatic behavior and poor prognosis. We constructed an
      adenovirus expressing a secretory adaptor capable of retargeting adenovirus to
      EGFR, resulting in a more than 150-fold increase in gene transfer. A replication
      competent dual-virus system secreting the adaptor displayed increased oncolytic
      potency in vitro and therapeutic gain in vivo. This approach could translate into
      increased efficacy and specificity in the treatment of EGFR overexpressing human
      cancers.

PMID- 11522630
TI  - scid Thymocytes with TCRbeta gene rearrangements are targets for the oncogenic
      effect of SCL and LMO1 transgenes.
AB  - SCL and LMO1 were both discovered by virtue of their activation by
      chromosomaltranslocation in patients with T-cell acute lymphoblastic leukemia (T
      ALL). Overexpression of SCL and LMO1 in the thymus of transgenic mice leads to T
      ALL at a young age. scid (severe combined immunodeficient) mice are unable to
      efficiently recombine antigen receptor genes and consequently display a
      developmental block at the CD4-CD8- to CD4+CD8+ transition. To test the
      hypothesis that this developmental block would protect SCL/LMO1 transgenic mice
      from developing T-ALL, we crossed the SCL and LMO1 transgenes onto a scid
      background. The age of onset for T-ALL in the SCL/LMO1/scid mice was
      significantly delayed (P < 0.001) compared with SCL/LMO1/wild-type mice.
      Intriguingly, all of the SCL/LMO1/scid malignancies displayed clonal, in-frame
      TCRbeta gene rearrangements. Taken together, these findings suggest that the
      "leaky" scid thymocyte that undergoes a productive TCRbeta gene rearrangement is
      susceptible to the oncogenic action of SCL and LMO1 and additionally suggests
      that TCRbeta gene rearrangements may be required for the oncogenic action of SCL
      and LMO1.

PMID- 11522631
TI  - Human Ogg1, a protein involved in the repair of 8-oxoguanine, is inhibited by
      nitric oxide.
AB  - NO-mediated inhibition of base excision DNA repair may potentiate oxidativeDNA
      damage in cells and could be relevant to carcinogenesis associated with chronic
      inflammation. Because 8-oxoguanine, a ubiquitous oxidative DNA lesion, is
      repaired predominantly by human 8-oxoguanine glycosylase (hOgg1), our aim was to
      determine whether NO directly inhibits its repair activity. Neither induction of
      NO-generating enzyme inducible NO synthase nor treatment with S-nitroso-N-acetyl
      D-L-pencillamine altered expression of hOgg1 in a human cholangiocarcinoma cell
      line (KMBC). In contrast, both treatments completely inhibited activity of hOgg1
      immunoprecipitated from KMBC cells overexpressing hOgg1 and in a cell-free
      system. Both NO and peroxynitrite were capable of inhibiting hOgg1 activity.
      Inhibition of hOgg1 protein was characterized by formation of S-nitrosothiol
      adducts and loss/ejection of zinc ions. Our data indicate that NO, an
      inflammatory mediator, directly inhibits a key base excision repair enzyme
      (hOgg1) responsible for base excision repair of 8-oxoguanine. These data support
      the concept that NO-mediated inhibition of DNA contributes to the mutagenic
      environment of chronic inflammation.

PMID- 11522632
TI  - Carbonic anhydrase (CA IX) expression, a potential new intrinsic marker of
      hypoxia: correlations with tumor oxygen measurements and prognosis in locally
      advanced carcinoma of the cervix.
AB  - There is increasing evidence that hypoxia-regulated gene expression influences
      tumor aggressiveness, contributing to the poorer outcome of patients with hypoxic
      tumors. The role of the transcriptional complex hypoxia-inducible factor-1 as an
      important mediator of hypoxia-regulated gene expression is one of the best
      documented pathways. Recently, it has emerged that certain tumor-associated
      carbonic anhydrases (CAs) can be added to the list of known hypoxia-inducible
      factor-responsive genes. Here we show that the immunohistochemical expression of
      the tumor-associated CA IX is correlated with the level of hypoxia in human
      cervical tumors. We performed a prospective study in 68 patients where needle
      electrodes were used to make direct measurements of tumor oxygenation levels. CA
      IX expression was evaluated immunohistochemically in pretreatment tumor biopsies.
      There was a significant positive correlation between the level of tumor hypoxia
      (HP5) and the extent of CA IX expression. A retrospective study of 130 squamous
      cell cervical carcinomas demonstrated that a semiquantitative immunohistochemical
      analysis of CA IX expression in tumor biopsies is a significant and independent
      prognostic indicator of overall survival and metastasis-free survival after
      radiation therapy. These studies provide clinical evidence that CA IX expression
      is up-regulated in hypoxic human cervical tumors and is associated with a poor
      prognosis. CA IX may act as an intrinsic marker of tumor hypoxia and poor outcome
      after radiation therapy. The level of CA IX expression may be used to aid in the
      selection of patients who would benefit most from hypoxia-modification therapies
      or bio-reductive drugs.

PMID- 11522633
TI  - Interstitial fluid pressure predicts survival in patients with cervix cancer
      independent of clinical prognostic factors and tumor oxygen measurements.
AB  - The purpose of this study was to determine the independent prognostic
      significanceof interstitial fluid pressure (IFP) measurements in cervix cancer. A
      total of 102 patients with newly diagnosed cervix cancer were accrued to this
      prospective study. There were 31 International Federation of Gynecology and
      Obstetrics stage IB or IIA tumors, 40 IIB tumors, and 31 IIIB tumors. The median
      size was 5 cm (range, 2-10 cm). Pelvic lymphadenopathy was identified
      radiographically in 20 patients. IFP was measured at examination under anesthesia
      using a wick-in-needle technique. Multiple measurements were made in each tumor.
      The mean IFP in individual tumors ranged from -3 to 48 mm Hg, and the median for
      the entire cohort was 19 mm Hg. Treatment consisted of external beam and
      intracavitary radiation without chemotherapy. Median follow-up was 2.5 years. The
      3-year disease-free survival of all of the patients was 53%. Disease-free
      survival was 34% in patients with IFP >19 mm Hg, and 68% in those with lower IFP
      (P = 0.002). To evaluate rigorously the independent prognostic significance of
      IFP measurements relative to established clinical factors, a multivariate model
      was first developed using stepwise selection of clinical covariates. Tumor size
      (P = 0.0003) and pelvic lymph node status (P = 0.0016) comprised the clinical
      model. IFP, when added to this model, provided additional independent prognostic
      information (P = 0.0013). IFP was also significant (P = 0.0027) when the clinical
      factors and hypoxic proportion as determined with the Eppendorf electrode were
      analyzed together. Patients with high IFP were more likely to recur both locally
      and at distant sites. This study is the first to document a strong, independent
      prognostic importance of pretreatment IFP measurements in cervix cancer. Patients
      with high IFP are significantly more likely than those with low IFP to recur
      after radiotherapy and die of progressive disease, independent of clinical
      prognostic factors and the results of tumor oxygen measurements.

PMID- 11522634
TI  - Secondary lymphoid organ chemokine reduces pulmonary tumor burden in spontaneous
      murine bronchoalveolar cell carcinoma.
AB  - The antitumor efficiency of secondary lymphoid organ chemokine (SLC), a CC
      chemokine that chemoattracts both dendritic cells (DCs) and T lymphocytes,was
      evaluated in SV40 large T-antigen transgenic mice that develop bilateral
      multifocal pulmonary adenocarcinomas. Injection of recombinant SLC in the
      axillary lymph node region led to a marked reduction in tumor burden with
      extensive lymphocytic and DC infiltration of the tumors and enhanced survival.
      SLC injection led to significant increases in CD4 and CD8 lymphocytes as well as
      DC at the tumor sites, lymph nodes, and spleen. The cellular infiltrates were
      accompanied by the enhanced elaboration of Type 1 cytokines and the
      antiangiogenic chemokines IFN-gamma inducible protein 10, and monokine induced by
      IFN-gamma (MIG). In contrast, lymph node and tumor site production of the
      immunosuppressive cytokine transforming growth factor beta was decreased in
      response to SLC treatment. In vitro, after stimulation with irradiated autologous
      tumor, splenocytes from SLC-treated mice secreted significantly more IFN-gamma
      and granulocyte macrophage colony-stimulating factor, but reduced levels of
      interleukin 10. Significant reduction in tumor burden in a model in which tumors
      develop in an organ-specific manner provides a strong rationale for additional
      evaluation of SLC in regulation of tumor immunity and its use in lung cancer
      immunotherapy.

PMID- 11522635
TI  - Mechanisms associated with tumor vascular shut-down induced by combretastatin A-4
      phosphate: intravital microscopy and measurement of vascular permeability.
AB  - The tumor vascular effects of the tubulin destabilizing agent disodium
      combretastatinA-4 3-O-phosphate (CA-4-P) were investigated in the rat P22 tumor
      growing in a dorsal skin flap window chamber implanted into BD9 rats. CA-4-P is
      in clinical trial as a tumor vascular targeting agent. In animal tumors, it can
      cause the shut-down of blood flow, leading to extensive tumor cell necrosis.
      However, the mechanisms leading to vascular shut-down are still unknown. Tumor
      vascular effects were visualized and monitored on-line before and after the
      administration of two doses of CA-4-P (30 and 100 mg/kg) using intravital
      microscopy. The combined effect of CA-4-P and systemic nitric oxide synthase
      (NOS) inhibition using N(omega)-nitro-L-arginine (L-NNA) was also assessed,
      because this combination has been shown previously to have a potentiating effect.
      The early effect of CA-4-P on tumor vascular permeability to albumin was
      determined to assess whether this could be involved in the mechanism of action of
      the drug. Tumor blood flow reduction was extremely rapid after CA-4-P treatment,
      with red cell velocity decreasing throughout the observation period and dropping
      to <5% of the starting value by 1 h. NOS inhibition alone caused a 50% decrease
      in red cell velocity, and the combined treatment of CA-4-P and NOS inhibition was
      approximately additive. The mechanism of blood flow reduction was very different
      for NOS inhibition and CA-4-P. That of NOS inhibition could be explained by a
      decrease in vessel diameter, which was most profound on the arteriolar side of
      the tumor circulation. In contrast, the effects of CA-4-P resembled an acute
      inflammatory reaction resulting in a visible loss of a large proportion of the
      smallest blood vessels. There was some return of visible vasculature at 1 h after
      treatment, but the blood in these vessels was static or nearly so, and many of
      the vessels were distended. The hematocrit within larger draining tumor venules
      tended to increase at early times after CA-4-P, suggesting fluid loss from the
      blood. The stacking of red cells to form rouleaux was also a common feature,
      coincident with slowing of blood flow; and these two factors would lead to an
      increase in viscous resistance to blood flow. Tumor vascular permeability to
      albumin was increased to approximately 160% of control values at 1 and 10 min
      after treatment. This could lead to an early decrease in tumor blood flow via an
      imbalance between intravascular and tissue pressures and/or an increase in blood
      viscosity as a result of increased hematocrit. These results suggest a mechanism
      of action of CA-4-P in vivo. Combination of CA-4-P with a NOS inhibitor has an
      additive effect, which it may be possible to exploit therapeutically.

PMID- 11522636
TI  - Amifostine protects against early but not late toxic effects of doxorubicin in
      infant rats.
AB  - The improved prognosis and increased expected lifetime among long-term survivors
      of childhood malignancies have made these patients especially sensitiveto the
      late toxicity of cancer therapy and prone to secondary malignancies. Recently,
      new strategies aiming to protect against cancer treatment toxicity have been
      developed, including the drug amifostine (Ethyol), which is suggested to protect
      normal tissues from the toxic effects of radiation and cytotoxic agents. In the
      present study, the possible protective effect of amifostine against toxicity
      induced by a single injection of doxorubicin (3 mg/kg) in immature rats was
      evaluated. Specifically, we evaluated the protection against long-term toxicity
      and the effects of amifostine on growing immature tissues. Amifostine (50-200
      mg/kg) given 15 min before doxorubicin had a significant protective effect
      against doxorubicin-induced early alopecia in young rats. Significant protection
      against cataract formation was obtained by the use of low-dose amifostine (50
      mg/kg). However, amifostine did not protect young rats against the late toxic
      effect of doxoubicin on linear growth, body weight, plasma leptin levels, and
      heart or testicular tissue. Worrisome, and in contrast to earlier studies in
      adult rats, an increased doxorubicin toxicity actually was observed and mortality
      was increased when the higher doses of amifostine (100-200 mg/kg) were used. The
      present results suggest that more data from growing immature animal models are
      needed to analyze the safety of amifostine treatment and its mechanisms of action
      before wider clinical use of this drug in pediatric cancer patients is
      recommended.

PMID- 11522637
TI  - A hepatocellular carcinoma-specific adenovirus variant, CV890, eliminates distant
      human liver tumors in combination with doxorubicin.
AB  - Hepatocellular carcinoma (HCC) is the third leading cause of cancer death in the
      world. Tumor resection remains the only curative treatment but is often not
      possible because of advanced stage and frequently unsuccessful because of
      intrahepatic or distant tumor recurrence. alpha-Fetoprotein (AFP), a tumor marker
      currently used for the diagnosis and management of HCC, is an oncofetal protein
      expressed in a majority of HCCs but rarely in normal hepatocytes. Because AFP
      gene expression is tightly regulated at the level of transcription, AFP
      transcriptional regulatory elements (TRE) are excellent candidates for generating
      HCC-specific oncolytic adenoviruses. We devised a new strategy for the AFP TRE to
      control an artificial E1A-IRES-E1B bicistronic cassette in an adenovirus 5 vector
      (Ad5) and constructed an HCC-specific oncolytic virus, CV890. In vitro, CV890
      expression of the E1A and E1B genes, virus replication, and cytopathic effects
      were examined by Northern blot, Western blot, virus yield assay, and 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay in AFP-producing cell
      lines (HepG2, Huh7, Hep3B, PLC/PRF/5, and SNU449), non-AFP-producing cell lines
      (Sk-Hep-1, Chang liver cell, LNCaP, HBL-100, PA-1, UM-UC-3, SW 780, Colo 201, and
      U118 MG), and non-AFP-producing human primary cells (lung fibroblast, bladder
      smooth muscle, and mammary epithelial). CV890 efficiently replicates in and
      destroys AFP-producing HCC cells as well as wild-type Ad5, but replication is
      highly attenuated in non-AFP-producing HCC cells or non-HCC cells. CV890 produced
      5,000-100,000-fold less virus than wild-type Ad5 in non-AFP-producing cells.
      CV890 was attenuated 100-fold more than CV732, a virus containing the AFP TRE
      driving the E1A gene alone, in non-AFP-producing cells. These studies
      demonstrated that expression of both E1A and E1B genes under the control of a
      bicistronic AFP-E1A-IRES-E1B cassette yielded improvements in virus specificity
      equivalent to driving the E1A and E1B genes with two independent TREs yet
      requires only one TRE thereby conserving genomic space within the virus.
      Significantly, CV890 produced nearly the same yield of virus in cells that
      produced AFP over a 75-fold range, from a low of 60 ng AFP/10(6) cells/10 days to
      as high as 4585 ng AFP/10(6) cells/10 days. In vivo, antitumor efficacy of CV890
      was examined in BALB/c-nu/nu mice containing large s.c. HepG2 or Hep3B tumor
      xenografts. Tumor volume of distant xenografts dropped below baseline 4 weeks
      after a single i.v. injection. Combination of CV890 with doxorubicin demonstrated
      synergistic antitumor efficacy, yielding complete elimination of distant Hep3B
      tumors 4 weeks after a single i.v. administration of both compounds. Our results
      support the clinical development of CV890 as an antineoplastic agent for the
      treatment of localized or metastatic HCC.

PMID- 11522638
TI  - Apoptotic signaling in polyamine analogue-treated SK-MEL-28 human melanoma cells.
AB  - N(1),N(11)-Diethylnorspermine (DENSPM) is a polyamine analogue with
      clinicalrelevance as an experimental anticancer agent and the ability to elicit a
      profound apoptotic response in certain cell types. Here, we characterize the
      polyamine effects and apoptotic signaling events initiated by treatment of SK-MEL
      28 human melanoma with 10 microM DENSPM. Maximal induction of the polyamine
      catabolic enzyme spermidine/spermine N(1)-acetyltransferase (SSAT) and polyamine
      pool depletion were seen by 16 h, whereas early apoptosis was first apparent at
      36 h. Intermediate events related to apoptotic signaling were sought between 16
      and 36 h. A loss of mitochondrial transmembrane potential (Deltapsi(m)) beginning
      at 24 h was followed by the release of cytochrome c into the cytosol at 30 h.
      Loss of mitochondrial integrity was accompanied by caspase-3 activation and
      poly(ADP-ribose) polymerase digestion from 30 to 36 h. The caspase inhibitor Z
      Asp-2,6-dichlorobenzoyloxymethylketone rendered cells resistant to analogue
      induced caspase-3 activation and reduced the apoptotic response in a dose
      dependent manner. Because polyamine reduction achieved by inhibitors of polyamine
      biosynthesis inhibited growth but did not cause apoptosis, we looked for
      alternative polyamine-related events, focusing on induction of SSAT. Three DENSPM
      analogues that differentially induced SSAT activity but similarly depleted
      polyamine pools revealed a close correlation between enzyme induction and
      cytochrome c release, caspase activation, and apoptosis. Dose-dependent
      inhibition of polyamine oxidase, an enzyme that oxidizes acetylated polyamines
      generated by SSAT and releases toxic by-products such as H(2)O(2) and aldehydes,
      prevented cytochrome c release, caspase activation, and apoptosis. Taken
      together, the findings indicate that DENSPM-induced apoptosis is at least
      partially initiated via massive induction of SSAT and related oxidative events
      and subsequently mediated by the mitochondrial apoptotic signaling pathway as
      indicated by cytochrome c release and caspase activation.

PMID- 11522639
TI  - Tumor cell lysate-pulsed human dendritic cells induce a T-cell response against
      pancreatic carcinoma cells: an in vitro model for the assessment of tumor
      vaccines.
AB  - Dendritic cells (DCs) are potent antigen-presenting cells and play a pivotal role
      in T cell-mediated immunity. DCs have been shown to induce strong antitumor
      immune responses in vitro and in vivo, and their efficacy is being investigated
      in clinical trials. Compared with vaccination strategies directed against a
      single tumor antigen, tumor-cell lysate as the source of antigen offers the
      potential advantage of inducing a broad T-cell response against multiple known,
      as well as unknown, tumor-associated antigens expressed by the individual tumor.
      We used pancreatic carcinoma cell lines to develop an in vitro model for
      monitoring T-cell responses induced by lysate-pulsed DCs. Monocyte-derived DCs of
      HLA-A2(+) donors were pulsed with lysate generated from the HLA-A2(+) pancreatic
      carcinoma cell line Panc-1. In some experiments, the immunogenic protein keyhole
      limpet hemocyanin (KLH) was added to the lysate. Subsequently, the antigen-loaded
      DCs were activated with tumor necrosis factor-alpha and prostaglandin E(2).
      Autologous mononuclear cells were cocultured with DCs in the presence of low-dose
      interleukin (IL)-2 and IL-7 and were restimulated weekly with new DCs. High
      levels of IL-12 and IFN-gamma could be detected in the supernatants, indicating a
      T-helper type 1-type immune response. This cytokine profile was associated with
      the expression of the activation marker CD69 on both T helper and CTLs and with
      an antigen-induced proliferative T-cell response. After 4 weeks, CTL-mediated
      cytotoxicity was assessed. Tumor cell lysis was specific for Panc-1 tumor cells
      and was MHC class I-restricted. Cytokine secretion, CD69 expression of T cells,
      and antigen-induced T-cell proliferation correlated with the cytotoxic activity
      and were more pronounced when KLH was added to the lysate. This is the first
      study to show that T cells specific for pancreatic carcinoma cells can be
      generated in vitro by lysate-pulsed DCs and that the T-cell response can be
      enhanced by KLH. This in vitro model can be applied to compare different
      strategies in the development of DC-based tumor vaccines.

PMID- 11522640
TI  - Immune and clinical responses in patients with metastatic melanoma to CD34(+)
      progenitor-derived dendritic cell vaccine.
AB  - Immunization to multiple defined tumor antigens for specific immune therapy of
      human cancer has thus far proven difficult. Eighteen HLA A*0201(+) patients with
      metastatic melanoma received injections s.c. of CD34(+)progenitor-derived
      autologous dendritic cells (DCs), which included Langerhans cells. DCs were
      pulsed with peptides derived from four melanoma antigens [(MelAgs) MelanA/MART-1,
      tyrosinase, MAGE-3, and gp100], as well as influenza matrix peptide (Flu-MP) and
      keyhole limpet hemocyanin (KLH) as control antigens. Overall immunological
      effects were assessed by comparing response profiles using marginal likelihood
      scores. DC injections were well tolerated except for progressive vitiligo in two
      patients. DCs induced an immune response to control antigens (KLH, Flu-MP) in 16
      of 18 patients. An enhanced immune response to one or more MelAgs was seen in
      these same 16 patients, including 10 patients who responded to >2 MelAgs. The two
      patients failing to respond to both control and tumor antigens experienced rapid
      tumor progression. Of 17 patients with evaluable disease, 6 of 7 patients with
      immunity to two or less MelAgs had progressive disease 10 weeks after study
      entry, in contrast to tumor progression in only 1 of 10 patients with immunity to
      >2 MelAgs. Regression of >1 tumor metastases were observed in seven of these
      patients. The overall immunity to MelAgs after DC vaccination is associated with
      clinical outcome (P = 0.015).

PMID- 11522641
TI  - Multidrug resistance-associated protein 3 is a tumor rejection antigen recognized
      by HLA-A2402-restricted cytotoxic T lymphocytes.
AB  - The identification of tumor rejection antigens recognized by CTLs and its
      application in peptide-based specific immunotherapy against melanomas have been
      extensively investigated in the past decade. However, only a small number of
      studies regarding these issues in other epithelial cancers have been reported. In
      this study, we show that a multidrug resistance-associated protein 3 (MRP3) is a
      tumor rejection antigen recognized by HLA-A2402-restricted CTLs established from
      T cells infiltrating into lung adenocarcinoma. MRP3 is expressed in differing
      quantities in tumor cells of various tissue types and origins. Four dominant MRP3
      derived antigenic peptides that are recognized by the CTLs have been identified,
      each possessing in vitro immunogenicity. Namely, these four peptides (MRP3-503,
      MRP3-692, MRP3-765, and MRP3-1293) can induce peptide-specific CTLs after in
      vitro stimulation with these peptides in peripheral blood mononuclear cell
      cultures of HLA-A24(+) cancer patients, with the CTLs expressing cytotoxicity
      against HLA-A2402(+) MRP3(+) tumor cells but not against either HLA-A2402(-) or
      MRP3(-) target cells. The peptide specificity of the cytotoxicity of the CTLs was
      further confirmed by using peptide-loaded HLA-A24(+) EBV-transformed B cells.
      Widespread MRP3 expression in various tumor cell lines and tumor tissues at the
      mRNA level was confirmed. Furthermore, reactivities of the MRP3-peptide-induced
      CTLs against tumor cells correlated with MRP3 expression in the tumor cells.
      These results suggest that MRP3 and its derived peptides described in the present
      paper are potential candidates for cancer vaccines in regard to HLA-A24(+)
      patients with various tumors, particularly for those tumors that show anticancer
      drug resistance.

PMID- 11522642
TI  - p63 expression is associated with p53 loss in oral-esophageal epithelia of p53
      deficient mice.
AB  - The p53 gene family, comprising p53, p63, and p73, has overlapping and
      distinctive functional roles. These members share structural similarities
      allowing for dynamic interplay in the activation of genes that are important in
      development and key cellular functions, such as the induction of apoptosis.
      Whereas p53 is a classical tumor suppressor gene, p63 and p73 do not share this
      feature in cancer formation and progression. The compensation in the expression
      level of these members in a background that is deficient for one of them has not
      been examined previously. Given the importance of p63 in the development and
      differentiation of oral-esophageal stratified squamous epithelia and the absence
      of oral-esophageal tumors in p53-null mice, we postulated and describe herein
      that p63 expression is associated with the loss of p53 in a p53-deficient
      background. Both full-length and amino-truncated forms of p63 are expressed and
      increased in oral-esophageal epithelia of p53-null mice when compared with wild
      type mice, and the induction of p21 may potentially be preserved through the
      increase of p63.

PMID- 11522643
TI  - Prediction of sensitivity of esophageal tumors to adjuvant chemotherapy by cDNA
      microarray analysis of gene-expression profiles.
AB  - We applied cDNA microarray analyses of 9216 genes to establish a genetic method
      for predicting the outcome of adjuvant chemotherapy to esophageal cancers. We
      analyzed expression profiles of 20 esophageal cancer tissues from patients who
      were treated with the same adjuvant chemotherapy after removal of tumor by
      operation, and we attempted to find genes associated with the duration of
      survival after surgery. By comparing expression profiles of those cancer tissues,
      we identified by statistical analysis 52 genes that were likely to be correlated
      with prognosis and possibly with sensitivity/resistance to the anticancer drugs.
      We also developed a drug response score based on the differential expression of
      these genes, and we found a significant correlation between the drug response
      score and individual patients' prognoses. Our results indicated that this scoring
      system, based on microarray analysis of selected genes, is likely to have great
      potential for predicting the prognosis of individual cancer patients with the
      adjuvant chemotherapy.

PMID- 11522644
TI  - MLL-ENL causes a reversible and myc-dependent block of myelomonocytic cell
      differentiation.
AB  - The translocation t(11;19) is a recurrent feature of a subgroup of acute
      leukemias occurring in infants. This event fuses the genes MLL and ENL and
      creates the leukemogenic oncoprotein MLL-ENL. We studied the effect of retroviral
      MLL-ENL expression in primary mouse hematopoietic cells and show here that MLL
      ENL requires the oncoprotein Myc to establish a reversible differentiation arrest
      of a myelomonocytic precursor population. MLL-ENL-transduced cells proliferated
      as immature myeloid cells in the presence of interleukin 3. The addition of
      granulocyte colony-stimulating factor reversed the maturation block set by MLL
      ENL and induced the development of mature granulocytes and macrophages
      accompanied by growth arrest. Gene expression analysis indicated a down
      regulation of the proto-oncogene c-myc and of several c-myc target genes during
      granulocyte colony-stimulating factor-mediated differentiation. The role of c-myc
      in the MLL-ENL transformation pathway was tested by modulating the effective Myc
      protein concentrations in MLL-ENL transduced cells. Cotransduction of dominant
      negative Myc neutralized the MLL-ENL effect and precluded transformation. In
      contrast, constitutive expression of Myc cooperated with MLL-ENL and caused the
      transformation of a cell population with an irreversible maturation arrest.

PMID- 11522645
TI  - Inverse regulation of cyclin B1 by c-Myc and p53 and induction of tetraploidy by
      cyclin B1 overexpression.
AB  - We have shown previously that mitotic spindle inhibitors allow the c
      Myconcoprotein to uncouple mitosis from DNA synthesis, resulting in the
      acquisition of tetraploidy. This can also occur in the absence of spindle
      inhibition if c-Myc deregulation is combined with inactivation of the p53 tumor
      suppressor. Under these conditions, cyclin B1 protein is induced but retains its
      normal cell cycle regulation. We now show that the cyclin B1 promoter is directly
      but oppositely regulated by c-Myc and p53. Enforced expression of cyclin B1 also
      induces tetraploidy, either after mitotic spindle inhibition or in the absence of
      such inhibition if cyclin B1 is coexpressed with c-Myc. Cyclin B1 represents a
      new class of c-Myc target genes that is also regulated by p53. It is also the
      first identified downstream effector of c-Myc able to produce the chromosomal
      instability that characterizes virtually all tumor cells.

PMID- 11522646
TI  - Role of HPC2/ELAC2 in hereditary prostate cancer.
AB  - The HPC2/ELAC2 gene on chromosome 17p was recently identified as a candidate gene
      for hereditary prostate cancer (HPC). To confirm these findings, we screened 300
      prostate cancer patients (2 affected members/family) from 150 families with HPC
      for potential germ-line mutations using conformation-sensitive gel
      electrophoresis, followed by direct sequence analysis. The minimum criteria for
      our families with HPC was the presence of 3 affected men with prostate cancer. A
      total of 23 variants were identified, including 13 intronic and 10 exonic
      changes. Of the 10 exonic changes, 1 truncating mutation was identified, a
      Glu216Stop nonsense mutation. This nonsense variant was found in 2 of 3 affected
      men in a single family. The remaining nine alterations included five missense,
      three silent, and one variant in the 3' untranslated region. To additionally test
      for potential associations of polymorphic variants and increased risk for
      disease, we genotyped two common polymorphisms, Ser217Leu and Ala541Thr, in 446
      prostate cancer patients from 164 families with HPC and 502 population-based
      controls. The frequency of the Leu217 variant was similar for patients (32.3%)
      and controls (31.8%), as was the frequency of the Thr541 variant (5.4% among
      patients versus 5.2% among controls). In contrast to previous reports, we found
      no association of the joint effects of Leu271 and Thr541 (odds ratio, 1.04; 95%
      confidence interval, 0.57-1.89). Overall, our results did not reveal any
      association between these two common polymorphisms and the risk for HPC. The
      finding of a nonsense mutation in the HPC2/ELAC2 gene confirms its potential role
      in genetic susceptibility to prostate cancer. However, our data also suggest that
      germ-line mutations of the HPC2/ELAC2 are rare in HPC and that the variants
      Leu217 and Thr541 do not appear to influence the risk for HPC. Cumulatively,
      these results suggest that alterations within the HPC2/ELAC2 gene play a limited
      role in genetic susceptibility to HPC.

PMID- 11522647
TI  - Activated extracellular signal-regulated kinases: association with epidermal
      growth factor receptor/transforming growth factor alpha expression in head and
      neck squamous carcinoma and inhibition by anti-epidermal growth factor receptor
      treatments.
AB  - The expression of the activated mitogen-activated kinases/extracellular signal
      regulated kinases (ERKs) ERK1 and ERK2 was characterized in 101 humanhead and
      neck squamous carcinoma specimens. Activated ERK1/2were detected at different
      levels in the majority of these tumors, as assayed by immunostaining with an
      antibody specific for the dually phosphorylated and activated ERK1 and ERK2.
      ERK1/2 activation levels were higher in tumors with advanced regional lymph node
      metastasis (P = 0.048) and in relapsed tumors (P = 0.021). The expression of
      epidermal growth factor (EGF) receptor (P = 0.037), transforming growth factor
      alpha (TGF-alpha; P < 0.001), and HER2 (P = 0.066; positive trend) correlated
      with activation of ERK1/2. In a multivariate analysis, both TGF-alpha (P <
      0.0001) and HER2 (P = 0.045) were independently correlated with ERK1/2
      activation. In turn, activation of ERK1/2 was associated with a higher Ki-67
      proliferative index (P = 0.002). In EGF receptor-dependent model cells (A431 and
      DiFi), a specific EGF receptor tyrosine kinase inhibitor ("Iressa"; ZD1839) and a
      chimeric anti-EGF receptor antibody ("Cetuximab"; C225) inhibited ERK 1/2
      activation at concentrations that inhibited autocrine cell proliferation. In
      patients on treatment with C225, the activation of ERK1/2 in skin, an EGF
      receptor-dependent tissue, was lower compared with control skin. Parallel changes
      were seen in keratinocyte Ki67 proliferation indexes in skin from C225-treated
      patients. Taken together, these studies provide support for a role of activation
      of ERK1/2 in head and neck squamous carcinoma and a correlation with EGF
      receptor/TGF-alpha expression. The inhibition of ERK1/2 activation in vitro and
      in vivo by compounds targeting the EGF receptor points to the interest of ERK1/2
      as potential surrogate markers of EGF-receptor signaling in clinical therapeutic
      studies.

PMID- 11522648
TI  - Endostatin-induced modulation of plasminogen activation with concomitant loss of
      focal adhesions and actin stress fibers in cultured human endothelial cells.
AB  - Endostatin, a M(r) 20,000 fragment of collagen XVIII, is able to inhibit
      angiogenesis and induce apoptosis in endothelial cells in vivo. We analyzed the
      effectsof recombinant endostatin on human microvascular endothelial cells,
      focusing on pericellular plasminogen activation and its targeting by the focal
      adhesion-associated cytoskeletal structures. Analysis of the proteolytic
      plasminogen activator system revealed that endostatin modulates the distribution
      of soluble and cell surface-associated urokinase-type plasminogen activator (uPA)
      and plasminogen activator inhibitor, type 1 (PAI-1). Casein zymographic and
      immunoprecipitation analyses indicated that endostatin exerts its effects by
      decreasing the levels of soluble uPA and PAI-1 and their complexes in a dose
      dependent manner. Immunofluorescence analysis of cell surface-associated uPA
      indicated that endostatin treatment caused the redistribution of receptor-bound
      uPA from focal contacts, resulting in diffuse cell surface staining. In
      accordance with this observation, immunofluorescence staining of the urokinase
      receptor revealed that endostatin treatment removed uPAR from focal adhesions.
      Accordingly, endostatin caused a rapid disassembly of focal adhesions as observed
      by immunofluorescence analysis of the focal adhesion proteins vinculin and
      paxillin. A prominent change in the cytoskeletal architecture was observed as the
      actin stress fiber network was dissociated in response to endostatin treatment.
      The effect of focal adhesion disassembly was reversible, persisting from 1 h up
      to 6 h. Our results suggest that the antiangiogenic activity of endostatin
      involves the modulation of focal adhesions and actin stress fibers and the down
      regulation of the urokinase plasminogen activator system.

PMID- 11522649
TI  - Role of signal transducer and activator of transcription 5 in nucleophosmin/
      anaplastic lymphoma kinase-mediated malignant transformation of lymphoid cells.
AB  - The NPM/ALK fusion gene, formed by the t(2;5) translocation in anaplastic large
      cell lymphoma, encodes a M(r) 75,000 hybrid protein that containsthe amino
      terminal portion of the nucleolar phosphoprotein nucleophosmin(NPM) joined to the
      entire cytoplasmic portion of the receptor tyrosine kinase anaplastic lymphoma
      kinase (ALK). NPM/ALK encodes a constitutively activated tyrosine kinase that
      belongs to the family of tyrosine kinases activated by chromosomal translocation.
      Our studies show that NPM/ALK, similar to other members of this family, activates
      signal transducer and activator of transcription 5 (STAT5) and that this
      activation is essential for lymphomagenesis. NPM/ALK-mediated activation of STAT5
      was demonstrated by detection of: (a) constitutive tyrosine phosphorylation and
      enhanced DNA binding ability of STAT5 in NPM/ALK-transformed cells; and (b)
      NPM/ALK-dependent stimulation of STAT5-mediated transactivation of the beta
      casein promoter. Retroviral infection of NPM/ALK+ cells with a dominant-negative
      STAT5B mutant (STAT5-DNM) inhibited the antiapoptotic activity of NPM/ALK in
      growth factor and serum-free medium. In addition, STAT5-DNM inhibited
      proliferation and diminished the clonogenic properties of NPM/ALK-positive cells.
      Finally, SCID mice injected with NPM/ALK+ cells infected with a virus carrying
      STAT5-DNM survived significantly longer than mice inoculated with NPM/ALK+ cells
      infected with the empty virus. Necropsy identified a widespread ALK+ lymphoma in
      lymph nodes and liver of the affected animals. Together, our data indicate that
      NPM/ALK-induced activation of STAT5 may play an important role in NPM/ALK
      mediated lymphomagenesis.

PMID- 11522650
TI  - Mapping extracellular pH in rat brain gliomas in vivo by 1H magnetic resonance
      spectroscopic imaging: comparison with maps of metabolites.
AB  - The value of extracellular pH (pH(e)) in tumors is an important factor in
      prognosisand choice of therapy. We demonstrate here that pH(e) can be mappedin
      vivo in a rat brain glioma by (1)H magnetic resonance spectroscopic imaging (SI)
      of the pH buffer (+/-)2-imidazole-1-yl-3-ethoxycarbonylpropionic acid (IEPA).
      (1)H SI also allowed us to map metabolites, and, to better understand the
      determinants of pH(e), we compared maps of pH(e), metabolites, and the
      distribution of the contrast agent gadolinium1,4,7,10-tetraazacyclododecane
      N,N',N",N"'-tetraaceticacid (Gd-DOTA). C6 cells injected in caudate nuclei of
      four Wistar rats gave rise to gliomas of approximately 10 mm in diameter. Three
      mmols of IEPA were injected in the right jugular vein from t = 0 to t = 60 min.
      From t = 50 min to t = 90 min, spin-echo (1)H SI was performed with an echo time
      of 40 ms in a 2.5-mm slice including the glioma (nominal voxel size, 2.2 microl).
      IEPA resonances were detected only within the glioma and were intense enough for
      pH(e) to be calculated from the chemical shift of the H2 resonance in almost all
      voxels of the glioma. (1)H spectroscopic images with an echo time of 136 ms were
      then acquired to map metabolites: lactate, choline-containing compounds (tCho),
      phosphocreatine/creatine, and N-acetylaspartate. Finally, T(1)-weighted imaging
      after injection of a bolus of Gd-DOTA gave a map indicative of extravasation. On
      average, the gradient of pH(e) (measured where sufficient IEPA was present) from
      the center to the periphery was not statistically significant. Mean pH(e) was
      calculated for each of the four gliomas, and the average was 7.084 +/- 0.017 (+/-
      SE; n = 4 rats), which is acid with respect to pH(e) of normal tissue. After
      normalization of spectra to their water peak, voxel-by-voxel comparisons of peak
      areas showed that N-acetylaspartate, a marker of neurons, correlated negatively
      with IEPA (P < 0.0001) and lactate (P < 0.05), as expected of a glioma surrounded
      by normal tissue. tCho (which may indicate proliferation) correlated positively
      with pH(e) (P < 0.0001). Lactate correlated positively with tCho (P < 0.0001),
      phosphocreatine/creatine (P < 0.001), and Gd-DOTA (P < 0.0001). Although lactate
      is exported from cells in association with protons, within the gliomas, no
      evidence was observed that pH(e) was significantly lower where lactate
      concentration was higher. These results suggest that lactate is produced mainly
      in viable, well-perfused, tumoral tissue from which proton equivalents are
      rapidly cleared.

PMID- 11522651
TI  - HOXB7: a key factor for tumor-associated angiogenic switch.
AB  - We had demonstrated previously a functional bridge between altered homebox (HOX)
      gene expression and tumor progression through HOXB7 transactivation of basic
      fibroblast growth factor. Here, we have studied whether HOXB7, in addition to
      basic fibroblast growth factor, may induce other genes directly or indirectly
      related to neoangiogenesis and tumor invasion. Parental, beta-galactosidase
      transduced, and HOXB7-transduced SkBr3 cell lines were examined for the
      expression of several growth factors and growth factor receptors involved in the
      proliferative and angiogenic processes. Vascular endothelial growth factor,
      melanoma growth-stimulatory activity/growth-related oncogenene alpha, interleukin
      8, and angiopoietin-2 were up-regulated by HOXB7 transduction. The exception was
      angiopoietin-1 expression that was abrogated. Additional analyses included the
      expression levels of enzymes such as matrix metalloprotease (MMP)-2 and MMP-9 and
      heparanase, capable of proteolytic degradation of extracellular matrix and
      basement membranes. Results showed an induction of only MMP-9. The functional
      implication of such a finding was tested using an in vitro coculture assay in a
      three-dimensional matrix. A delay of differentiation with persistent nests of
      proliferating cells was found in endothelial cells cocultured with HOXB7
      transduced SkBr3 cells. Tumorigenicity of these cells has been evaluated in vivo.
      Xenograft into athymic nude mice showed that SkBr3/HOXB7 cells developed tumors
      in mice, either irradiated or not, whereas parental SkBr3 cells did not show any
      tumor take unless mice were sublethally irradiated. Comparison of tumor nodules
      for vascularization by CD-31 and CD-34 immunostaining revealed an increased
      number of blood vessels in tumors expressing HOXB7. Together, the results
      indicate HOXB7 as a key factor up-regulating a variety of proangiogenic stimuli.
      Thus, HOXB7 gene or protein is a target to aim at to inhibit tumor-associated
      neoangiogenesis, considering the number and the redundancy of proangiogenic
      molecules that should be targeted one by one to theoretically achieve the same
      effect.

PMID- 11522652
TI  - Overexpression of IRF9 confers resistance to antimicrotubule agents in breast
      cancer cells.
AB  - IRF9/p48/ISGF3gamma (IRF9) is an IFN regulatory factor that mediates signaling by
      type I IFNs (IFNalpha and IFNbeta). After single-step selection of breast
      adenocarcinoma cells in paclitaxel, differential display and single gene analysis
      demonstrated that transcriptional activation of IRF9 and other IFN-responsive
      genes, independent of IFN, corresponded with resistance to antimicrotubule
      agents. Transient overexpression of IRF9 reproduced the drug-resistance phenotype
      and induced expression of IFN-responsive genes. However, drug resistance was not
      induced by overexpression of Stat1 or Stat2, or treatment with IFNalpha per se.
      Using a donor-matched array of cDNA prepared from human tumor and normal tissue
      from a variety of organs, we observed overexpression of IRF9 in approximately one
      half of breast and uterine tumors, which indicated that IRF9 may be important in
      signaling in these tumor types. These data identify a novel IFN-independent role
      for IRF9 in the development of resistance to antimicrotubule agents in breast
      tumor cells and may link downstream mediators of IFN signaling to drug resistance
      in human cancers.

PMID- 11522653
TI  - Constitutive expression of hypoxia-inducible factor-1alpha renders pancreatic
      cancer cells resistant to apoptosis induced by hypoxia and nutrient deprivation.
AB  - Hypovasculature is an outstanding characteristic of pancreatic cancers in imaging
      diagnosis, suggesting that blood supply is poor in pancreatic cancer tissues.
      Despite poor blood supply, pancreatic cancer cells survive and proliferate in
      severe hypoxia and nutrient deprivation. To demonstrate how pancreatic cancer
      cells adapt themselves to hypoxia and nutrient deprivation, we investigated the
      expression of hypoxia-inducible factor 1alpha (HIF-1alpha) protein and HIF-1
      inducible genes in human pancreatic cancer cell lines in comparison with other
      cancer cell lines. We found that HIF-1alpha protein was constitutively expressed
      in 15 of 20 pancreatic cancer cell lines (75%) but in none of other cancer cell
      lines tested in this study. The cells with constitutive expression of HIF-1alpha
      were more resistant to apoptosis induced by hypoxia and glucose deprivation than
      those without constitutive expression of HIF-1alpha. Transfection with HIF-1alpha
      transformed the latter cells resistant to apoptosis and increased in vivo
      tumorigenicity. Furthermore, anaerobic metabolism-associated genes, Glut1 and
      aldolase A, were more highly expressed in the cells with constitutive expression
      of HIF-1alpha than in the cells without it. These results suggest that
      constitutive expression of HIF-1alpha contributes to the survival and
      proliferation of pancreatic cancer cells in hypoxia and glucose deprivation
      through the activation of anaerobic metabolism.

PMID- 11522654
TI  - The role of the DNA mismatch repair system in the cytotoxicity of the
      topoisomerase inhibitors camptothecin and etoposide to human colorectal cancer
      cells.
AB  - The DNA mismatch repair (MMR) system is involved in the correction of base/base
      mismatches and insertion/deletion loops arising during replication. In addition,
      some of the MMR components participate in recombination and double-strand break
      repair as well as cell cycle regulation and apoptosis. The inactivation of MMR
      genes, usually hMSH2 or hMLH1, is associated with human colorectal cancers and is
      responsible for the characteristic microsatellite instability (MSI)+ phenotype of
      these tumors. Because MMR is assumed to modulate cytotoxicity to various
      chemotherapeutic agents that act upon DNA, our objectives have been to define its
      possible involvement in the cytotoxicity of topoisomerase inhibitors. We have
      shown that colorectal cancer cell lines defective in DNA MMR exhibit an increased
      sensitivity to both camptothecin, a topoisomerase I inhibitor, and etoposide, a
      topoisomerase II inhibitor. Sensitivity to these drugs cannot be predicted by
      measuring endogenous levels of topoisomerase I and II. Our results also indicate
      that neither p53 status, nor cell cycle alterations correlate with the
      sensitivity of colorectal cancer cells to topoisomerase inhibitors. On the other
      hand, our data showing that resistance to these drugs can be achieved by the
      functional complementation of hMLH1 in an hMLH1-defective cell line have allowed
      us to establish that MMR is a critical determinant for chemosensitivity.
      Interestingly, our observations provide the rationale for the better
      responsiveness of MSI+ tumors to CPT-11, a camptothecin derivative, which we have
      observed in patients with metastatic colorectal cancers.

PMID- 11522655
TI  - Suppression of beta-catenin inhibits the neoplastic growth of APC-mutant colon
      cancer cells.
AB  - Mutations involving the adenomatous polyposis coli (APC) tumor
      suppressorgene/beta-catenin signaling pathway have been identified in the
      majority of colon carcinomas. However, the role of aberrant beta-catenin
      signaling in the neoplastic growth of APC-mutant colon cancer cells has not been
      directly studied. To address this question, antisense oligonucleotides have been
      used to specifically down-regulate beta-catenin expression in APC-mutant human
      colon carcinoma cells. Antisense-mediated suppression of beta-catenin inhibits
      the in vitro proliferation, anchorage-independent growth, and cellular
      invasiveness of APC-mutant human colon carcinoma cells. The systemic
      administration of beta-catenin antisense oligonucleotides down-regulates beta
      catenin expression in vivo in human colon cancer xenografts in nude mice. Such
      treatment inhibits the tumorigenic growth of colon cancer xenografts and can
      completely eradicate tumors in some treated animals. These studies formally
      demonstrate the critical role of beta-catenin signaling in the neoplastic growth
      of APC-mutant colon cancer cells and suggest that strategies targeting beta
      catenin may be of use in the therapy of colon cancer.

PMID- 11522656
TI  - Activation of extracellular signal-regulated kinase and c-Jun-NH(2)-terminal
      kinase but not p38 mitogen-activated protein kinases is required for RRR-alpha
      tocopheryl succinate-induced apoptosis of human breast cancer cells.
AB  - RRR-alpha-tocopherol succinate (vitamin E succinate, VES) is a potent, selective
      apoptotic agent for cancer cells but not normal cells. VES has been shown to
      inhibit the growth of a wide variety of tumor cells in cell culture and animal
      models. Studies addressing mechanisms of action of VES-induced apoptosis have
      identified transforming growth factor-beta, Fas/CD95-APO-1, and mitogen-activated
      protein kinase (MAPK) signaling pathway involvement. Here we show that MAPKs, the
      extracellular signal-regulated kinases (ERK), and the stress-activated protein
      kinases, c-Jun NH2-terminal kinases (JNK), but not p38, are critical mediators in
      VES-induced apoptosis of human breast cancer MDA-MB-435 cells. VES activates
      ERK1/2 and JNK both in level and duration of kinase activity. Expression of
      dominant negative mutants of ERK1, MAPK/ERK activator-1, or JNK1 but not p38
      blocked phosphorylation of the substrate glutathione S-transferase-c-Jun and
      inhibited VES-induced apoptosis. Increased phosphorylation and transactivation
      activity of nuclear transcription factors c-Jun, ATF-2, and Elk-1 are observed
      after VES treatments; however, only c-Jun and ATF-2 appear to be involved in VES
      induced apoptosis based on antisense blockage experiments. Collectively, these
      results imply a critical role for ERK1 and JNK1 but not p38 in VES-induced
      apoptosis of human MDA-MB-435 breast cancer cells.

PMID- 11522657
TI  - Impact of ionizing radiation and genetic background on mammary tumorigenesis in
      p53-deficient mice.
AB  - Loss of p53 function is known to compromise cell cycle regulation, inductionof
      apoptosis, and DNA damage repair and can facilitate neoplastic transformation of
      cells. Mutations in the p53 gene are identified frequently in breast carcinomas.
      Li-Fraumeni patients inheriting a mutant p53 allele have an increased risk for
      developing tumors including breast cancer. Although mouse lines carrying
      mutations in the p53 gene have been generated, they die primarily of lymphoma and
      thus to date provide a limited model for the study of this disease and the role
      of p53 in nonfamilial breast cancer. An increasing body of literature suggests
      that the incidence of various tumors is determined largely by the genetic
      background on which mutations are studied. In addition, population studies and
      studies in animals suggest that environmental factors, together with genetic
      factors, determine overall risk for development of specific types of tumors. We
      therefore examined the impact of genetic background together with exposure to
      ionizing radiation on the development of tumors, particularly mammary tumors, in
      p53-deficient animals. We report here that modifier alleles present in the BALB/c
      strain increase the incidence of hemangiosarcomas [15 of 53 (28.3%); P = 0.0007]
      in p53(-/-) mice above rates reported previously in p53(-/-) mice on a mixed
      background as compared to the incidence observed in DBA/p53(-/-) mice. However,
      no increase in the frequency of mammary tumors is seen in these mice or in p53(-/
      ) DBA/2 animals, nor was an increase in mammary tumors observed in the DBA/2
      p53(+/-) mice, even after exposure to 5 Gy of whole-body ionizing radiation. In
      contrast, a significant increase in the incidence of mammary tumors was observed
      in similarly treated BALB/c p53(+/-) mice (37.3% versus 6.8%; P = 0.0007). This
      was accompanied by a comparable decrease in the incidence of lymphomas. These
      results show that environmental agents together with genetic factors can increase
      the frequency and decrease the latency of mammary tumors, leading to an incidence
      similar to that observed in Li-Fraumeni syndrome. Furthermore, it suggests that
      the risk of development of a particular type of tumor by individuals deficient in
      p53 after exposure to damaging agents can be influenced by modifier alleles.

PMID- 11522658
TI  - ErbB2/neu kinase modulates cellular p27(Kip1) and cyclin D1 through multiple
      signaling pathways.
AB  - It is well established that ErbB1 and ErbB2 can cooperate in mammary epithelial
      cell transformation. Therefore, to understand how ErbB1/ErbB2 signaling
      contributes to this process, we used the ErbB kinase inhibitor AG1478in ErbB2
      dependent BT-474 and SKBR-3 human breast cancer cells. These cells overexpress
      ErbB2 and also display moderate levels of ErbB1. Treatment with AG1478 resulted
      in rapid ErbB2 dephosphorylation, reversible G(1) arrest, and interruption of
      constitutive mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3
      kinase (PI3K)/Akt signaling. Consequently, both MAPK-dependent transcription of
      cyclin D1 and phosphorylation of the cyclin-dependent kinase (Cdk) inhibitor p27
      were inhibited. The inhibition of PI3K/Akt resulted in increased activity of
      glycogen synthase kinase-3beta, which phosphorylated cyclin D1, potentially
      reducing its steady-state levels. The loss of cyclin D1 reduced the amount of
      cyclin D1/Cdk4 complexes that can sequester p27 in the cytosol. This plus the
      reduced phosphorylation of p27 by MAPK enhanced the stability of p27 that
      associated with nuclear Cdk2 at high stoichiometry and inhibited its kinase
      activity. Antisense p27 oligonucleotides decreased p27 levels and abrogated the
      G(1) arrest induced by AG1478. Similarly, infection with an adenovirus encoding
      inducible cyclin D1 also counteracted the antiproliferative effect of AG1478.
      These data imply that: (a) modulation of both p27 and cyclin D1 are required for
      the growth arrest that results from blockade of the ErbB2 kinase; and (b) ErbB2
      overexpressing cells use both MAPK and PI3K/Akt to modulate p27 and cyclin D1
      and, hence, subvert the G(1)-to-S transition.

PMID- 11522659
TI  - The mechanism of the growth-inhibitory effect of coxsackie and adenovirus
      receptor (CAR) on human bladder cancer: a functional analysis of car protein
      structure.
AB  - The coxsackie and adenovirus receptor (CAR) is identified as a high-affinity
      receptor for adenovirus type 5. We observed that invasive bladder cancer
      specimens had significantly reduced CAR mRNA levels compared with superficial
      bladder cancer specimens, which suggests that CAR may play a role in the
      progression of bladder cancer. Elevated CAR expression in the T24 cell line (CAR
      negative cells) increased its sensitivity to adenovirus infection and
      significantly inhibited its in vitro growth, accompanied by p21 and
      hypophosphorylated retinoblastoma accumulation. Conversely, decreased CAR levels
      in both RT4 and 253J cell lines (CAR-positive cells) promoted their in vitro
      growth. To unveil the mechanism of action of CAR, we showed that the
      extracellular domain of CAR facilitated intercellular adhesion. Furthermore,
      interrupting intercellular adhesion of CAR by a specific antibody alleviates the
      growth-inhibitory effect of CAR. We also demonstrated that both the transmembrane
      and intracellular domains of CAR were critical for its growth-inhibitory
      activity. These data indicate that the cell-cell contact initiated by membrane
      bound CAR can elicit a negative signal cascade to modulate cell cycle regulators
      inside the nucleus of bladder cancer cells. Therefore, the presence of CAR cannot
      only facilitate viral uptake of adenovirus but also inhibit cell growth. These
      results can be integrated to formulate a new strategy for bladder cancer therapy.

PMID- 11522660
TI  - The neuropeptide pituitary adenylate cyclase-activating polypeptide and islet
      function.
AB  - The neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) is
      ubiquitously distributed in both the central and peripheral nervous systems and
      exerts a variety of effects. PACAP is a neuropeptide in pancreatic islets, where
      it has been suggested as a parasympathetic and sensory neurotransmitter. PACAP
      stimulates insulin secretion in a glucose-dependent manner, by an effect executed
      mainly through augmenting the formation of cAMP and stimulating the uptake of
      calcium. Accumulating evidence in animal studies points to a physiological
      importance of PACAP in the regulation of the insulin response to feeding. This
      review summarizes the current knowledge of islet actions and mechanisms and the
      function of PACAP.

PMID- 11522661
TI  - A role for hormone-sensitive lipase in glucose-stimulated insulin secretion: a
      study in hormone-sensitive lipase-deficient mice.
AB  - Endogenous lipid stores are thought to be involved in the mechanism whereby the
      beta-cell adapts its secretory capacity in obesity and diabetes. In addition,
      hormone-sensitive lipase (HSL) is expressed in beta-cells and may provide fatty
      acids necessary for the generation of coupling factors linking glucose metabolism
      to insulin release. We have recently created HSL-deficient mice that were used to
      directly assess the role of HSL in insulin secretion and action. HSL(-/-) mice
      were normoglycemic and normoinsulinemic under basal conditions, but showed an
      approximately 30% reduction of circulating free fatty acids (FFAs) with respect
      to control and heterozygous animals after an overnight fast. An intraperitoneal
      glucose tolerance test revealed that HSL-null mice were glucose-intolerant and
      displayed a lack of a rise in plasma insulin after a glucose challenge.
      Examination of plasma glucose during an insulin tolerance test suggested that HSL
      null mice were insulin-resistant, because plasma glucose was barely lowered after
      the injection of insulin. Freshly isolated islets from HSL-deficient mice
      displayed elevated secretion at low (3 mmol/l) glucose, failed to release insulin
      in response to high (20 mmol/l) glucose, but had a normal secretion when
      challenged with elevated KCl. The phenotype of heterozygous mice with respect to
      the measured parameters in vitro was similar to that of wild type. Finally, the
      islet triglyceride content of HSL(-/-) mice was 2-2.5 fold that in HSL(-/+) and
      HSL(+/+) animals. The results demonstrate an important role of HSL and endogenous
      beta-cell lipolysis in the coupling mechanism of glucose-stimulated insulin
      secretion. The data also provide direct support for the concept that some lipid
      molecule(s), such as FFAs, fatty acyl-CoA or their derivatives, are implicated in
      beta-cell glucose signaling.

PMID- 11522662
TI  - Isolation and functional characterization of recombinant GAD65 autoantibodies
      derived by IgG repertoire cloning from patients with type 1 diabetes.
AB  - The generation of human monoclonal autoantibodies is critical for understanding
      humoral immune responses in autoimmunity. In this study, we isolated the first
      human recombinant antibodies to glutamate decarboxylase (rGAD65ab) by IgG
      repertoire cloning, phage display of Fab fragments, and biopanning from two
      patients at onset of type 1 diabetes. We demonstrate that natural Ig heavy- and
      light-chain pairings of autoantibodies can be isolated by the recombinant
      approach and have a major selection advantage over other rGAD65ab. Among eight
      rGAD65ab, three (rGAD65ab A-C) displayed all functional and structural properties
      of known disease-related GAD65ab, including reactivity in the enzyme-linked
      immunosorbent assay (ELISA), radioimmunoassay (RIA), islet cell antibody (ICA)
      test, and variable gene usage. Dominant epitope recognition was directed to the
      previously defined epitope EP-1 in the middle of GAD65, corroborating its
      immunodominance in the molecule. New features, such as assay-dependent GAD65
      reactivity and new epitope recognition, were observed in two rGAD65ab (D and E).
      These antibodies were positive in the GAD65 ELISA and ICA test but not in the
      GAD65 RIA, providing the first examples for ICA with incongruent results in solid
      phase and fluid-phase assays. In conclusion, phage display-derived antibodies
      reflected well the natural autoantibody response in type 1 diabetes and may allow
      further characterization of assay-dependent features of GAD65ab and the
      recognition of epitopes in solid- but not fluid-phase assays.

PMID- 11522663
TI  - Heme oxygenase-1 induction in islet cells results in protection from apoptosis
      and improved in vivo function after transplantation.
AB  - Transplantation of islets of Langerhans represents a viable therapeutic approach
      for the treatment of type 1 diabetes. Unfortunately, transplanted islets are
      susceptible to allogeneic recognition and rejection, recurrence of autoimmunity,
      and destruction by local inflammation at the site of implantation. The last of
      these phenomena might not only result in functional impairment and death of islet
      cells but could also contribute to amplifying the subsequent specific immune
      response. Induction of islet cell protection against inflammation could therefore
      be postulated to be a powerful means to improve overall graft fate. Heme
      oxygenase-1 (HO-1) has been described as an inducible protein capable of
      cytoprotection via radical scavenging and apoptosis prevention. The purpose of
      the present study was to analyze whether HO-1 upregulation in a beta-cell line
      and in freshly isolated murine islets could result in protection from apoptosis
      and improve in vivo functional performance. HO-1 upregulation was induced
      reproducibly with protoporphyrins and was correlated with protection from
      apoptosis induced in vitro with proinflammatory cytokines or Fas engagement.
      Furthermore, in vivo HO-1 upregulation resulted in improved islet function in a
      model of marginal mass islet transplantation in rodents. Strategies aimed at
      inducing HO-1 upregulation might result in improved success in islet
      transplantation.

PMID- 11522664
TI  - Autoreactive diabetogenic T-cells in NOD mice can efficiently expand from a
      greatly reduced precursor pool.
AB  - A broad repertoire of pancreatic beta-cell autoreactive T-cells normally
      contributes to the development of type 1 diabetes in NOD mice. However, it has
      been unknown if a large reduction in the precursor pool from which autoreactive T
      cells are drawn would inhibit the development of type 1 diabetes. To address this
      issue, we reduced the precursor frequency of autoreactive T-cells in NOD mice
      through allelic exclusion induced by transgenic expression of an H2-Db class I
      restricted T-cell receptor (TCR) specific for a pathologically irrelevant
      lymphocytic choriomeningitis virus (LCMV) peptide. TCR allelic exclusion greatly
      reduced the pool of T-cells from which diabetogenic effectors could be derived in
      these NODxLCMV TCR Tg mice. Surprisingly, this did not impair their type 1
      diabetes susceptibility. Furthermore, a diabetogenic CD8 T-cell population that
      is prevalent in standard NOD mice was present at essentially equivalent levels in
      pancreatic islets of NODxLCMV TCR Tg mice. Other data indicated that the
      antigenic specificity of these CD8 T-cells is primarily the function of a shared
      TCR-alpha chain. Although the percentage of TCR transgenic T-cells decreased in
      NOD versus B6,D2 control mice, much higher total numbers of both the TCR
      transgenic and the nontransgenic T-cells accumulated in the NOD strain. This
      transgenic T-cell accumulation in the absence of the cognate peptide indicated
      that the NOD genetic background preferentially promotes a highly efficient
      antigen-independent T-cell expansion. This might allow diabetogenic T-cells in
      NOD mice to undergo an efficient expansion before encountering antigen, which
      would represent an important and previously unconsidered aspect of pathogenesis.

PMID- 11522665
TI  - Decrease in beta-cell mass leads to impaired pulsatile insulin secretion, reduced
      postprandial hepatic insulin clearance, and relative hyperglucagonemia in the
      minipig.
AB  - Most insulin is secreted in discrete pulses at an interval of approximately 6
      min. Increased insulin secretion after meal ingestion is achieved through the
      mechanism of amplification of the burst mass. Conversely, in type 2 diabetes,
      insulin secretion is impaired as a consequence of decreased insulin pulse mass.
      beta-cell mass is reported to be deficient in type 2 diabetes. We tested the
      hypothesis that decreased beta-cell mass leads to decreased insulin pulse mass.
      Insulin secretion was examined before and after an approximately 60% decrease in
      beta-cell mass achieved by a single injection of alloxan in a porcine model.
      Alloxan injection resulted in stable diabetes (fasting plasma glucose 7.4 +/- 1.1
      vs. 4.4 +/- 0.1 mmol/l; P < 0.01) with impaired insulin secretion in the fasting
      and fed states and during a hyperglycemic clamp (decreased by 54, 80, and 90%,
      respectively). Deconvolution analysis revealed a selective decrease in insulin
      pulse mass (by 54, 60, and 90%) with no change in pulse frequency. Rhythm
      analysis revealed no change in the periodicity of regular oscillations after
      alloxan administration in the fasting state but was unable to detect stable
      rhythms reliably after enteric or intravenous glucose stimulation. After alloxan
      administration, insulin secretion and insulin pulse mass (but not insulin pulse
      interval) decreased in relation to beta-cell mass. However, the decreased pulse
      mass (and pulse amplitude delivered to the liver) was associated with a decrease
      in hepatic insulin clearance, which partially offset the decreased insulin
      secretion. Despite hyperglycemia, postprandial glucagon concentrations were
      increased after alloxan administration (103.4 +/- 6.3 vs. 92.2 +/- 2.5 pg/ml; P <
      0.01). We conclude that an alloxan-induced selective decrease in beta-cell mass
      leads to deficient insulin secretion by attenuating insulin pulse mass, and that
      the latter is associated with decreased hepatic insulin clearance and relative
      hyperglucagonemia, thereby emulating the pattern of islet dysfunction observed in
      type 2 diabetes.

PMID- 11522666
TI  - Calpains play a role in insulin secretion and action.
AB  - Studies of the genetic basis of type 2 diabetes suggest that variation in the
      calpain-10 gene affects susceptibility to this common disorder, raising the
      possibility that calpain-sensitive pathways may play a role in regulating insulin
      secretion and/or action. Calpains are ubiquitously expressed cysteine proteases
      that are thought to regulate a variety of normal cellular functions. Here, we
      report that short-term (4-h) exposure to the cell-permeable calpain inhibitors
      calpain inhibitor II and E-64-d increases the insulin secretory response to
      glucose in mouse pancreatic islets. This dose-dependent effect is observed at
      glucose concentrations above 8 mmol/l. This effect was also seen with other
      calpain inhibitors with different mechanisms of action but not with cathepsin
      inhibitors or other protease inhibitors. Enhancement of insulin secretion with
      short-term exposure to calpain inhibitors is not mediated by increased responses
      in intracellular Ca2+ or increased glucose metabolism in islets but by
      accelerated exocytosis of insulin granules. In muscle strips and adipocytes,
      exposure to both calpain inhibitor II and E-64-d reduced insulin-mediated glucose
      transport. Incorporation of glucose into glycogen in muscle also was reduced.
      These results are consistent with a role for calpains in the regulation of
      insulin secretion and insulin action.

PMID- 11522667
TI  - Expression of the receptor tyrosine kinase KIT in mature beta-cells and in the
      pancreas in development.
AB  - In the pancreas, ligands of receptor tyrosine kinases (RTKs) are thought to be
      implicated in the development and function of the islets of Langerhans, which
      represent the endocrine part of the pancreas. In a previous study, we randomly
      screened by reverse transcriptase-polymerase chain reaction for RTKs expressed in
      the embryonic pancreas. One cDNA fragment that was cloned during this screen
      corresponded to the KIT receptor. The objective of the present study was to
      analyze the pattern of Kit expression in the pancreas. We demonstrated that Kit
      is expressed and functional in terms of signal transduction in the insulin
      producing cell line INS-1. Indeed, upon treatment with the KIT ligand (KITL), the
      extracellular signal-regulated protein kinase was phosphorylated, and the
      expression of early responsive genes was induced. We also demonstrated that Kit
      mRNAs are present in fetal and adult rat islets. We next used mice that had
      integrated the lacZ reporter gene into the Kit locus. In these mice, beta
      galactosidase (beta-gal) served as a convenient marker for expression of the
      endogenous Kit gene. Kit was found to be specifically transcribed in beta-cells
      (insulin-expressing cells), whereas no expression was found in other endocrine
      cell types or in the exocrine tissue. Interestingly, not all mature beta-cells
      expressed Kit, indicating that Kit is a marker of a subpopulation of beta-cells.
      Finally, by following beta-gal expression in the pancreas during fetal life, we
      found that at E14.5, Kit is expressed in both insulin- and glucagon-expressing
      cells present at that stage, and also in a specific cell population present in
      the epithelium that stained negative for endocrine markers. These data suggest
      that these Kit-positive/endocrine-negative cells could represent a subpopulation
      of endocrine cell precursors.

PMID- 11522668
TI  - A low-affinity Ca2+-dependent association of calmodulin with the Rab3A effector
      domain inversely correlates with insulin exocytosis.
AB  - The stimulus-response coupling pathway for glucose-regulated insulin secretion
      has implicated a rise in cytosolic [Ca2+]i as a key factor to induce insulin
      exocytosis. However, it is unclear how elevated [Ca2+]i communicates with the
      pancreatic beta-cell's exocytotic apparatus. As Rab3A is a model protein involved
      in regulated exocytosis, we have focused on its role in regulating insulin
      exocytosis. By using a photoactivatable cross-linking synthetic peptide that
      mimics the effector domain of Rab3A and microsequence analysis, we found
      calmodulin to be a major Rab3A target effector protein in pancreatic beta-cells.
      Coimmunoprecipitation analysis from pancreatic islets confirmed a Rab3A
      calmodulin interaction in vivo, and that it inversely correlated with insulin
      exocytosis. Calmodulin affected neither GTPase nor guanine nucleotide exchange
      activity of Rab3A. The calmodulin-Rab3A interaction was pH- and Ca2+-dependent,
      and it was preferential for GTP-bound Rab3A. However, Rab3A affinity for
      calmodulin was relatively low (Kd = 18-22 micromol/l at 10(-5) mol/l [Ca2+]) and
      competed by other calmodulin-binding proteins that had higher affinity (e.g.,
      Ca2+/calmodulin-dependent protein kinase-2 [CaMK-2] [Kd = 300-400 nmol/l at 10(
      5) mol/l [Ca2+]]). Moreover, the Ca2+ dependence of the calmodulin-Rab3A
      interaction (K0.5 = 15-18 micromol/l [Ca2+], maximal at 100 micromol/l [Ca2+])
      was significantly lower compared with that of the calmodulin-CaMK-2 association
      (K0.5 = 40 micromol/l [Ca2+], maximal at 1 mmol/l [Ca2+]). The data suggested
      that a transient Rab3A-calmodulin interaction might represent a means of
      directing calmodulin to the cytoplasmic face of a beta-granule, where it can be
      subsequently transferred for activation of other beta-granule-associated
      calmodulin-binding proteins as local [Ca2+]i rises to promote insulin exocytosis.

PMID- 11522669
TI  - Overexpression of metallothionein in pancreatic beta-cells reduces streptozotocin
      induced DNA damage and diabetes.
AB  - The release of reactive oxygen species (ROS) has been proposed as a cause of
      streptozotocin (STZ)-induced beta-cell damage. This initiates a destructive
      cascade, consisting of DNA damage, excess activation of the DNA repair enzyme
      poly(ADP-ribose) polymerase, and depletion of cellular NAD+. Metallothionein (MT)
      is an inducible antioxidant protein that has been shown to protect DNA from
      chemical damage in several cell types. Therefore, we examined whether
      overexpression of MT could protect beta-cell DNA and thereby prevent STZ-induced
      diabetes. Two lines of transgenic mice were produced with up to a 30-fold
      elevation in beta-cell MT. Cultured islets from control mice and MT transgenic
      mice were exposed to STZ. MT was found to decrease STZ-induced islet disruption,
      DNA breakage, and depletion of NAD+. To assess in vivo protection, transgenic and
      control mice were injected with STZ. Transgenic mice had significantly reduced
      hyperglycemia. Ultrastructural examination of islets from STZ-treated mice showed
      that MT prevented degranulation and cell death. These results demonstrate that MT
      can reduce diabetes and confirm the DNA damage mechanism of STZ-induced beta-cell
      death.

PMID- 11522671
TI  - Use of a cDNA array for the identification of genes induced in islets of suckling
      rats by a high-carbohydrate nutritional intervention.
AB  - Four-day-old rat pups that are raised artificially on a high-carbohydrate (HC)
      milk formula immediately develop hyperinsulinemia, which persists into adulthood
      without any further nutritional stimulus. cDNA array analysis was used to
      identify large-scale changes in gene expression patterns in islets from 12- and
      100-day-old HC rats in response to the HC dietary modification during the
      suckling period. It was observed that the expression of several genes that belong
      to clusters involved in beta-cell development and/or beta-cell function was
      significantly upregulated in islets from 12- and 100-day-old HC rats. It is
      inferred that in addition to predicted changes in gene expression, for example
      preproinsulin gene, global changes in gene expression contribute to the
      hyperinsulinemic state in the HC rat.

PMID- 11522670
TI  - The generalized aminoaciduria seen in patients with hepatocyte nuclear factor
      1alpha mutations is a feature of all patients with diabetes and is associated
      with glucosuria.
AB  - Hepatocyte nuclear factor-1alpha (HNF-1alpha) mutations are the most common cause
      of maturity-onset diabetes of the young. HNF-1alpha homozygous knockout mice
      exhibit a renal Fanconi syndrome with glucosuria and generalized aminoaciduria in
      addition to diabetes. We investigated glucosuria and aminoaciduria in patients
      with HNF-1alpha mutations. Sixteen amino acids were measured in urine samples
      from patients with HNF-1alpha mutations, age-matched nondiabetic control
      subjects, and age-matched type 1 diabetic patients, type 2 diabetic patients, and
      patients with diabetes and chronic renal failure. The HNF-1alpha patients had
      glucosuria at lower glycemic control (as shown by HbA1c) than type 1 and type 2
      diabetic patients, consistent with a lower renal glucose threshold. The HNF
      1alpha patients had a generalized aminoaciduria with elevated levels of 14 of 16
      amino acids and an increased mean Z score for all amino acids compared with
      control subjects (0.66 vs. 0.00; P < 0.0005). Generalized aminoaciduria was also
      present in type 1 diabetic (Z score, 0.80; P < 0.0001), type 2 diabetic (Z score,
      0.71; P < 0.0002), and chronic renal failure (Z score, 0.65; P < 0.01) patients.
      Aminoaciduria was not associated with microalbuminuria or proteinuria but was
      associated with glucosuria (1.00 glucosuria vs. 0.19 no glucosuria; P = 0.002).
      In type 1 diabetic patients, urine samples taken on the same day showed
      significantly more aminoaciduria when glucosuria was present compared with when
      it was absent (P < 0.01). In conclusion, HNF-1alpha mutation carriers have a
      mutation-specific defect of proximal tubular glucose transport, resulting in
      increased glucosuria. In contrast, the generalized aminoaciduria seen in patients
      with HNF-1alpha mutations is a general feature of patients with diabetes and
      glucosuria. Glucose may depolarize and dissipate the electrical gradient of the
      sodium-dependent amino acid transporters in the proximal renal tubule, causing a
      reduction in amino acid resorption.

PMID- 11522672
TI  - Combined treatment with benzylamine and low dosages of vanadate enhances glucose
      tolerance and reduces hyperglycemia in streptozotocin-induced diabetic rats.
AB  - Semicarbazide-sensitive amine oxidase (SSAO) is highly expressed in adipose
      cells, and substrates of SSAO, such as benzylamine, in combination with low
      concentrations of vanadate strongly stimulate glucose transport and GLUT4
      recruitment in 3T3-L1 and rat adipocytes. Here we examined whether acute and
      chronic administration of benzylamine and vanadate in vivo enhances glucose
      tolerance and reduces hyperglycemia in diabetic rats. Acute intravenous
      administration of these drugs enhanced glucose tolerance in nondiabetic rats and
      in streptozotocin (STZ)-induced diabetic rats. This occurred in the absence of
      changes in plasma insulin concentrations. However, the administration of
      benzylamine or vanadate alone did not improve glucose tolerance. The improvement
      caused by benzylamine plus vanadate was abolished when rats were pretreated with
      the SSAO-inhibitor semicarbazide. Chronic administration of benzylamine and
      vanadate exerted potent antidiabetic effects in STZ-induced diabetic rats.
      Although daily administration of vanadate alone (50 and 25 micromol x kg(-1) x
      day(-1) i.p.) for 2 weeks had little or no effect on glycemia, vanadate plus
      benzylamine reduced hyperglycemia in diabetic rats, enhanced basal and insulin
      stimulated glucose transport, and upregulated GLUT4 expression in isolated
      adipocytes. In all, our results substantiated that acute and chronic
      administration of benzylamine with low dosages of vanadate have potent
      antidiabetic effects in rats.

PMID- 11522673
TI  - Interactions of impaired glucose transport and phosphorylation in skeletal muscle
      insulin resistance: a dose-response assessment using positron emission
      tomography.
AB  - It has been postulated that glucose transport is the principal site of skeletal
      muscle insulin resistance in obesity and type 2 diabetes, though a distribution
      of control between glucose transport and phosphorylation has also been proposed.
      The current study examined whether the respective contributions of transport and
      phosphorylation to insulin resistance are modulated across a dose range of
      insulin stimulation. Rate constants for transport and phosphorylation in skeletal
      muscle were estimated using dynamic positron emission tomography (PET) imaging of
      2-deoxy-2[18F]fluoro-D-glucose ([18F]FDG) during insulin infusions at three rates
      (0, 40, and 120 mU/m2 per min) in lean glucose-tolerant, obese glucose-tolerant,
      and obese type 2 diabetic subjects. Parallel studies of arteriovenous fractional
      extraction across the leg of [18F]FDG and [2-3H] glucose were performed to
      measure the "lumped constant" (LC) (i.e., the analog effect) for [18F]FDG to
      determine whether this value is affected by insulin dose or insulin resistance.
      The value of the LC was similar across insulin doses and groups. Leg glucose
      uptake (LGU) also provided a measure of skeletal muscle glucose metabolism
      independent of PET. [18F]FDG uptake determined by PET imaging strongly correlated
      with LGU across groups and across insulin doses (r = 0.81, P < 0.001). Likewise,
      LGU correlated with PET parameters of glucose transport (r = 0.67, P < 0.001) and
      glucose phosphorylation (r = 0.86, P < 0.001). Glucose transport increased in
      response to insulin in the lean and obese groups (P < 0.05), but did not increase
      significantly in the type 2 diabetic group. A dose-responsive pattern of
      stimulation of glucose phosphorylation was observed in all groups of subjects (P
      < 0.05); however, glucose phosphorylation was lower in both the obese and type 2
      diabetic groups compared with the lean group at the moderate insulin dose (P <
      0.05). These findings indicate an important interaction between transport and
      phosphorylation in the insulin resistance of obesity and type 2 diabetes.

PMID- 11522674
TI  - Adipocyte produces matrix metalloproteinases 2 and 9: involvement in adipose
      differentiation.
AB  - Adipocyte hypertrophy and hyperplasia together with angiogenesis contribute to
      the growth of the fat mass. Because changes in the extracellular matrix (ECM)
      components are often associated with such cellular remodeling, we studied the
      adipocyte expression of the matrix metalloproteinases (MMPs) 2 and 9, two key
      enzymes involved in the modulation of ECM. The present study provides the first
      evidence that human adipose tissue produces and secretes MMP-2 and -9 as shown by
      gelatin zymography analysis performed on media conditioned by human subcutaneous
      adipose tissue and human preadipocytes in primary cultures and by reverse
      transcriptase-polymerase chain reaction (RT-PCR) analysis on transcripts from
      mature human adipocytes. The further characterization performed on the murine
      3T3F442A preadipocyte cell line demonstrates that MMP expression, assessed by RT
      PCR and Western blot analysis, as well as activity, assessed by gelatin
      zymography analysis, increased during the adipocyte differentiation, whereas the
      expression of tissue inhibitor metalloproteinases 1 and 2 were abolished or not
      affected, respectively. Finally, preadipocyte treatment with MMP inhibitors such
      as batimastat and captopril, as well as neutralizing antibodies, markedly
      decreased adipocyte differentiation as demonstrated by the inhibition in the
      appearance of lipogenic (triglycerides) and lipolytic (glycerol release and
      hormone-sensitive lipase expression) markers. These data suggest that MMP-2 and 
      9 could be important key regulators of adipocyte differentiation. Thus, the
      adipocyte-derived MMPs might represent a new target for the inhibition of adipose
      tissue growth.

PMID- 11522675
TI  - Abnormal glucose handling by the kidney in response to hypoglycemia in type 1
      diabetes.
AB  - The frequent occurrence of hypoglycemia in people with type 1 diabetes is
      attributed to abnormalities in the blood glucose counterregulatory response. In
      view of recent findings indicating that the kidney contributes to prevent and
      correct hypoglycemia in healthy subjects, we decided to investigate the role of
      renal glucose handling in hypoglycemia in type 1 diabetes. Twelve type 1 diabetic
      patients and 14 age-matched normal individuals were randomized to
      hyperinsulinemic-euglycemic (n = 6 diabetic subjects and n = 8 control subjects)
      or hypoglycemic (n = 6 each) clamps with blood glucose maintained either stable
      near 100 mg/dl (5.6 mmol/l) or reduced to 54 mg/dl (3.0 mmol/l). All study
      subjects had their renal vein catheterized under fluoroscopy, and net renal
      glucose balance and renal glucose production and utilization rates were measured
      using a combination of arteriovenous concentration difference with stable isotope
      dilution technique. Blood glucose and insulin were comparable in both groups in
      all studies. In patients with diabetes, elevations in plasma glucagon,
      epinephrine, and norepinephrine were blunted, and both the compensatory rise in
      endogenous glucose production and in the net glucose output by the kidney seen in
      normal subjects with equivalent hypoglycemia were absent. Renal glucose balance
      switched from a mean +/- SE baseline net uptake of 0.6 +/- 0.4 to a net output of
      4.5 +/- 1.3 micromol x kg(-1) x min(-1) in normal subjects, but in patients with
      diabetes there was no net renal contribution to blood glucose during similar
      hypoglycemia (mean +/- SE net glucose uptake [baseline 0.7 +/- 0.4] remained at
      0.4 +/- 0.3 micromol x kg(-1) x min(-1) in the final 40 min of hypoglycemia; P <
      0.01 between groups). We conclude that adrenergic stimulation of glucose output
      by the kidney, which represents an additional defense mechanism against
      hypoglycemia in normal subjects, is impaired in patients with type 1 diabetes and
      contributes to defective glucose counterregulation.

PMID- 11522676
TI  - PPARgamma ligands increase expression and plasma concentrations of adiponectin,
      an adipose-derived protein.
AB  - Insulin resistance and its dreaded consequence, type 2 diabetes, are major causes
      of atherosclerosis. Adiponectin is an adipose-specific plasma protein that
      possesses anti-atherogenic properties, such as the suppression of adhesion
      molecule expression in vascular endothelial cells and cytokine production from
      macrophages. Plasma adiponectin concentrations are decreased in obese and type 2
      diabetic subjects with insulin resistance. A regimen that normalizes or increases
      the plasma adiponectin might prevent atherosclerosis in patients with insulin
      resistance. In this study, we demonstrate the inducing effects of
      thiazolidinediones (TZDs), which are synthetic PPARgamma ligands, on the
      expression and secretion of adiponectin in humans and rodents in vivo and in
      vitro. The administration of TZDs significantly increased the plasma adiponectin
      concentrations in insulin resistant humans and rodents without affecting their
      body weight. Adiponectin mRNA expression was normalized or increased by TZDs in
      the adipose tissues of obese mice. In cultured 3T3-L1 adipocytes, TZD derivatives
      enhanced the mRNA expression and secretion of adiponectin in a dose- and time
      dependent manner. Furthermore, these effects were mediated through the activation
      of the promoter by the TZDs. On the other hand, TNF-alpha, which is produced more
      in an insulin-resistant condition, dose-dependently reduced the expression of
      adiponectin in adipocytes by suppressing its promoter activity. TZDs restored
      this inhibitory effect by TNF-alpha. TZDs might prevent atherosclerotic vascular
      disease in insulin-resistant patients by inducing the production of adiponectin
      through direct effect on its promoter and antagonizing the effect of TNF-alpha on
      the adiponectin promoter.

PMID- 11522677
TI  - Reduced oral wound healing in the NOD mouse model for type 1 autoimmune diabetes
      and its reversal by epidermal growth factor supplementation.
AB  - Using the NOD mouse, a model for type 1 diabetes, we examined how reduced
      concentrations of epidermal growth factor (EGF) in the saliva, after onset of
      type 1 diabetes, affect oral wound healing. Diabetic NOD/LtJ mice on insulin
      therapy, prediabetic NOD/LtJ, and age- and sex-matched BALB/cJ mice were given a
      cutaneous tongue punch and allowed to undergo normal healing. With diabetes onset
      and a reduction in saliva-derived growth factor levels, the rate of tongue wound
      healing was reduced compared with nondiabetic NOD/LtJ and healthy BALB/cJ mice.
      Addition of exogenous EGF to the drinking water did not accelerate the rate of
      healing in BALB/cJ or prediabetic NOD/LtJ; however, diabetic NOD/LtJ mice
      exhibited accelerated wound healing similar to healthy mice. These results
      demonstrate that loss of growth factors from saliva is associated with profoundly
      reduced oral wound healing, suggesting that therapeutic treatment with topical
      delivery may be beneficial to patients with type 1 diabetes and oral wound
      complications.

PMID- 11522678
TI  - Glucose and palmitic acid induce degeneration of myofibrils and modulate
      apoptosis in rat adult cardiomyocytes.
AB  - Several studies support the concept of a diabetic cardiomyopathy in the absence
      of discernible coronary artery disease, although its mechanism remains poorly
      understood. We investigated the role of glucose and palmitic acid on
      cardiomyocyte apoptosis and on the organization of the contractile apparatus.
      Exposure of adult rat cardiomyocytes for 18 h to palmitic acid (0.25 and 0.5
      mmol/l) resulted in a significant increase of apoptotic cells, whereas increasing
      glucose concentration to 33.3 mmol/l for up to 8 days had no influence on the
      apoptosis rate. However, both palmitic acid and elevated glucose concentration
      alone or in combination had a dramatic destructive effect on the myofibrillar
      apparatus. The membrane-permeable C2-ceramide but not the metabolically inactive
      C2-dihydroceramide enhanced apoptosis of cardiomyocytes by 50%, accompanied by
      detrimental effects on the myofibrils. The palmitic acid-induced effects were
      impaired by fumonisin B1, an inhibitor of ceramide synthase. Sphingomyelinase,
      which activates the catabolic pathway of ceramide by metabolizing sphingomyeline
      to ceramide, did not adversely affect cardiomyocytes. Palmitic acid-induced
      apoptosis was accompanied by release of cytochrome c from the mitochondria.
      Aminoguanidine did not prevent glucose-induced myofibrillar degeneration,
      suggesting that formation of nitric oxide and/or advanced glycation end products
      play no major role. Taken together, these results suggest that in adult rat
      cardiac cells, palmitic acid induces apoptosis via de novo ceramide formation and
      activation of the apoptotic mitochondrial pathway. Conversely, glucose has no
      influence on adult cardiomyocyte apoptosis. However, both cell nutrients promote
      degeneration of myofibrils. Thus, gluco- and lipotoxicity may play a central role
      in the development of diabetic cardiomyopathy.

PMID- 11522679
TI  - Overexpression of Cu2+/Zn2+ superoxide dismutase protects against early diabetic
      glomerular injury in transgenic mice.
AB  - Ex vivo and in vitro observations implicate superoxide as a mediator of cell
      injury in diabetes, but in vivo evidence is lacking. In the current studies,
      parameters of glomerular injury were examined in hemizygous nondiabetic
      transgenic mice (SOD) and streptozotocin-diabetic (D) transgenic mice (D-SOD),
      which overexpress human cytoplasmic Cu2+/Zn2+ superoxide dismutase (SOD-1), and
      in corresponding wild-type littermates (WT, D-WT) after 4 months of diabetes. In
      both SOD and D-SOD mice, renal cortical SOD-1 activity was twofold higher than
      values in the WT mice; blood glucose and glycosylated hemoglobin (GHb) levels did
      not differ in the two diabetic groups. Urinary albumin excretion, fractional
      albumin clearance, urinary transforming growth factor-beta (TGF-beta) excretion,
      glomerular volume, glomerular content of immunoreactive TGF-beta, and collagen
      alpha1 (IV) and renal cortical malondialdehyde (MDA) levels were significantly
      higher in D-WT mice compared with corresponding values in D-SOD mice. Glomerular
      volume, glomerular content of TGF-beta and collagen IV, renal cortical MDA, and
      urinary excretion of TGF-beta in D-SOD mice did not differ significantly from
      corresponding values in either the nondiabetic SOD or WT mice. In separate groups
      of mice studied after 8 months of diabetes, mesangial matrix area, calculated as
      a fraction of total glomerular tuft area, and plasma creatinine were
      significantly higher in D-WT but not in D-SOD mice, compared with corresponding
      values in the nondiabetic mice. In vitro infection of mesangial cells (MC) with a
      recombinant adenovirus encoding human SOD-1 increased SOD-1 activity threefold
      over control cells and prevented the reduction of aconitase activity, an index of
      cellular superoxide, and the increase in collagen synthesis that otherwise
      occurred in control MC in response to culture with 300 or 500 mg/dl glucose.
      Thus, increases in cellular SOD-1 activity attenuate diabetic renal injury in
      vivo and also prevent stimulation of MC matrix protein synthesis induced in vitro
      by high glucose.

PMID- 11522680
TI  - Changes in matrix proteoglycans induced by insulin and fatty acids in hepatic
      cells may contribute to dyslipidemia of insulin resistance.
AB  - Insulin resistance and type 2 diabetes are associated with elevated circulating
      levels of insulin, nonesterified fatty acids (NEFAs), and lipoprotein remnants.
      Extracellular matrix proteoglycan (PG) alterations are also common in macro- and
      microvascular complications of type 2 diabetes. In liver, extracellular heparan
      sulfate (HS) PGs contribute to the uptake of triglyceride-rich lipoprotein
      remnants. We found that HepG2 cells cultured with 10 or 50 nmol/l insulin or 300
      micromol/l albumin-bound linoleic acid changed their PG secretion. The
      glycosaminoglycans (GAGs) of the secreted PGs from insulin-treated HepG2 cells
      were enriched in chondroitin sulfate (CS) PGs. In contrast, cells exposed to
      linoleic acid secreted PGs with decreased content of CS. Insulin caused a
      moderate increase in mRNA for versican (secreted CS PG), whereas linoleic acid
      markedly decreased mRNA for versican in HepG2 cells, as did the peroxisomal
      proliferator-activated receptor-alpha agonist bezafibrate. The effects of insulin
      or linoleic acid on syndecan 1, a cell surface HS PG, were similar to those on
      versican, but less pronounced. The livers of obese Zucker fa/fa rats, which are
      insulin-resistant and have high levels of insulin, NEFAs, and triglyceride-rich
      remnants, showed increased expression of CS PGs when compared with lean
      littermates. These changes in PG composition decreased the affinity of remnant
      beta-VLDL particles to PGs isolated from insulin-treated HepG2 cells and obese
      rat livers. The results indicated that insulin and NEFAs modulate the expression
      of PGs in hepatic cells. We speculate that in vivo this exchange of CS for HS may
      reduce the clearance of remnant beta-VLDLs and contribute to the dyslipidemia of
      insulin resistance.

PMID- 11522681
TI  - Depressed levels of Ca2+-cycling proteins may underlie sarcoplasmic reticulum
      dysfunction in the diabetic heart.
AB  - In view of the depressed sarcoplasmic reticulum (SR) Ca2+-pump and Ca2+-release
      activities in the diabetic heart and the critical role of phosphorylation in
      regulating the SR function, we examined the status of Ca2+-calmodulin-dependent
      protein kinase (CaMK) and cAMP-dependent protein kinase (PKA)-mediated
      phosphorylations in the diabetic heart. Diabetes was induced in male Sprague
      Dawley rats by an injection of streptozotocin (65 mg/kg i.v.), and the animals
      were killed 6 weeks later for assessment of the ventricular SR function.
      Depressed cardiac performance and SR Ca2+-uptake and -release activities in
      diabetic animals were accompanied by a significant decrease in the level of SR
      Ca2+-cycling proteins, such as ryanodine receptor, Ca2+-pump ATPase, and
      phospholamban. On the other hand, the CaMK- and PKA-mediated phosphorylations of
      these Ca2+-cycling proteins, the endogenous SR CaMK and PKA activities, and the
      endogenous SR and cytosolic phosphatase activities were increased in the diabetic
      heart. Treatment of 3-week diabetic animals with insulin partially or fully
      prevented the diabetes-induced changes in cardiac performance, SR Ca2+-uptake and
      -release activites, and SR protein content, whereas the diabetes-induced changes
      in SR CaMK- and PKA-mediated phosphorylations and activities, as well as
      phosphatase activities, were not significantly affected. These results suggest
      that the reduced content of the Ca2+-cycling proteins, unlike alterations in PKA
      and phosphatase activities, appear to be the major defect underlying SR
      dysfunction in the diabetic heart.

PMID- 11522682
TI  - Human fructosamine-3-kinase: purification, sequencing, substrate specificity, and
      evidence of activity in vivo.
AB  - Nonenzymatic glycation appears to be an important factor in the pathogenesis of
      diabetic complications. Key early intermediates in this process are
      fructosamines, such as protein-bound fructoselysines. In this report, we describe
      the purification and characterization of a mammalian fructosamine-3-kinase
      (FN3K), which phosphorylates fructoselysine (FL) residues on glycated proteins,
      to FL-3-phosphate (FL3P). This phosphorylation destabilizes the FL adduct and
      leads to its spontaneous decomposition, thereby reversing the nonenzymatic
      glycation process at an early stage. FN3K was purified to homogeneity from human
      erythrocytes and sequenced by means of electrospray tandem mass spectrometry. The
      protein thus identified is a 35-kDa monomer that appears to be expressed in all
      mammalian tissues. It has no significant homology to other known proteins and
      appears to be encoded by genomic sequences located on human chromosomes 1 and 17.
      The lability of FL3P, the high affinity of FN3K for FL, and the wide distribution
      of FN3K suggest that the function of this enzyme is deglycation of
      nonenzymatically glycated proteins. Because the condensation of glucose and
      lysine residues is an ubiquitous and unavoidable process in homeothermic
      organisms, a deglycation system mediated by FN3K may be an important factor in
      protecting cells from the deleterious effects of nonenzymatic glycation. Our
      sequence data of FN3K are in excellent agreement with a recent report on this
      enzyme by Delpierre et al. (Diabetes 49:1627-1634, 2000).

PMID- 11522683
TI  - Skeletal muscle of stroke-prone spontaneously hypertensive rats exhibits reduced
      insulin-stimulated glucose transport and elevated levels of caveolin and
      flotillin.
AB  - Insulin resistance is of major pathogenic importance in several common human
      disorders, but the underlying mechanisms are unknown. The stroke-prone
      spontaneously hypertensive (SHRSP) rat is a model of human insulin resistance and
      is characterized by reduced insulin-mediated glucose disposal and defective fatty
      acid metabolism in isolated adipocytes (Collison et al. [Diabetes 49:2222-2226,
      2000]). In this study, we have examined skeletal muscle and cultured skeletal
      muscle myoblasts for defects in insulin action in the male SHRSP rat model
      compared with the normotensive, insulin-sensitive control strain, Wistar-Kyoto
      (WKY). We show that skeletal muscle from SHRSP animals exhibits a marked decrease
      in insulin-stimulated glucose transport compared with WKY animals (fold increase
      in response to insulin: 1.4 +/- 0.15 in SHRSP, 2.29 +/- 0.22 in WKY; n = 4, P =
      0.02), but the stimulation of glucose transport in response to activation of AMP
      activated protein kinase was similar between the two strains. Similar reductions
      in insulin-stimulated glucose transport were also evident in myoblast cultures
      from SHRSP compared with WKY cultures. These differences were not accounted for
      by a reduction in cellular GLUT4 content. Moreover, analysis of the levels and
      subcellular distribution of insulin receptor substrates 1 and 2, the p85alpha
      subunit of phosphatidylinositol 3'-kinase, and protein kinase B (PKB)/cAKT in
      skeletal muscle did not identify any differences between the two strains; the
      insulin-dependent activation of PKB/cAKT was not different between the two
      strains. However, the total cellular levels of caveolin and flotillin, proteins
      implicated in insulin signal transduction/compartmentalization, were markedly
      elevated in skeletal muscles from SHRSP compared with WKY animals. Increased
      cellular levels of the soluble N-ethylmaleimide attachment protein receptor
      (SNARE) proteins syntaxin 4 and vesicle-associated membrane protein (VAMP)-2 were
      also observed in the insulin-resistant SHRSP strain. Taken together, these data
      suggest that the insulin resistance observed in the SHRSP is manifest at the
      level of skeletal muscle, that muscle cell glucose transport exhibits a blunted
      response to insulin but unchanged responses to activation of AMP-activated
      protein kinase, that alterations in key molecules in both GLUT4 trafficking and
      insulin signal compartmentalization may underlie these defects in insulin action,
      and that the insulin resistance of these muscles appears to be of genetic origin
      rather than a paracrine or autocrine effect, since the insulin resistance is also
      observed in cultured myoblasts over several passages.

PMID- 11522684
TI  - Mutational screening of the CART gene in obese children: identifying a mutation
      (Leu34Phe) associated with reduced resting energy expenditure and cosegregating
      with obesity phenotype in a large family.
AB  - Cocaine- and amphetamine-regulated transcript (CART) inhibits feeding and induces
      the expression of c-Fos in hypothalamic areas implicated in appetite regulation.
      Furthermore, the CART peptide is found in neurons regulating sympathetic outflow,
      which in turn play an integral role in regulating body temperature and energy
      expenditure. The CART gene was screened by single-strand conformation
      polymorphism and automatic sequencing in 130 (72 girls) unrelated obese Italian
      children and adolescents. Their Z-scores (mean +/- SD) of relative to BMI
      percentiles was 3.9 +/- 1.8, and the average age at obesity onset was 4.7 +/- 2.6
      years. Two previously described silent polymorphisms were found in the 3'
      untranslated region: an adenine deletion at position 1457 in 9 patients (allele
      frequency 0.035) and an A/G substitution at position 1475 in 11 patients (allele
      frequency 0.042). We found no difference between the obese patients heterozygous
      for one of these polymorphisms and those patients homozygous for the wild allele
      with respect to their age of obesity onset, BMI Z-scores, and leptin levels. A
      missense mutation of G729C resulting in the substitution of Leu with Phe at codon
      34, within the NH2-terminal CART region, has been detected in the heterozygous
      state in a 10-year-old obese boy who has been obese since the age of 2 years. The
      patient belongs to a large family of obese subjects. The mutation cosegregated
      with the severe obesity phenotype over three generations and was not found in the
      control population. Resting metabolic rates were lower than expected in the
      propositus (-14%) and his mother (-16%), who carried the mutation. Leucine at
      codon 34, conserved in this position in the human and in the rat sequences,
      immediately precedes a couple of lysine residues that may well represent a
      dibasic processing site. The Leu34Phe mutation might alter the susceptibility to
      proteolysis of this potential processing site, likely altering the CART effect on
      thermogenesis and energy expenditure.

PMID- 11522685
TI  - Functional significance of the UCSNP-43 polymorphism in the CAPN10 gene for
      proinsulin processing and insulin secretion in nondiabetic Germans.
AB  - Recently, an association of the G allele in UCSNP-43 of calpain 10 with type 2
      diabetes and decreased glucose disposal was reported. Calpain 10 is also
      expressed in pancreatic islets. It is not known, however, whether and how this
      polymorphism contributes to the biological variation of beta-cell function. We
      studied 73 nondiabetic subjects from the southwest region of Germany (G/G, n =
      41; G/A, n = 29; and A/A, n = 3) using a modified hyperglycemic clamp (10 mmol/l
      glucose, added glucagon-like peptide 1, final arginine bolus). The genotype
      distribution was not different between subjects with normal glucose tolerance (n
      = 56) and those with impaired glucose tolerance (n = 17; P = 0.74, chi2 test).
      First-phase insulin secretion (adjusted for sex and insulin sensitivity from
      hyperglycemic clamp) was greater in G/G (2,747 +/- 297 pmol/min) than in G/A +
      A/A (1,612 +/- 156 pmol/min, P = 0.003). Insulin secretion in response to
      arginine (adjusted for insulin sensitivity) was also greater in G/G (9,648 +/-
      1,186 pmol/min) than in G/A + A/A (5,686 +/- 720 pmol/min, P = 0.04). The acute
      poststimulus proinsulin-to-insulin ratio was lower in G/G (1.6 +/- 0.4% first
      phase; 1.6 +/- 0.2% arginine) than in G/A + A/A (4.0 +/- 0.5% first phase, P <
      0.001; 2.5 +/- 0.4% arginine, P = 0.03). In conclusion, it appears unlikely that
      any association of the UCSNP-43 polymorphism alone with type 2 diabetes involves
      impairment of insulin secretion in our population of German Caucasians. This may
      be entirely different with specific haplotype combinations.

PMID- 11522686
TI  - Role of allelic variants Gly972Arg of IRS-1 and Gly1057Asp of IRS-2 in moderate
      to-severe insulin resistance of women with polycystic ovary syndrome.
AB  - To assess the role of insulin receptor, insulin receptor substrate (IRS)-1, and
      IRS-2 genes in insulin resistance, we explored the genomic DNA in women with
      polycystic ovary syndrome (PCOS) and a variable degree (mean +/- SE) of insulin
      resistance (homeostasis model assessment index for insulin resistance [HOMA(IR)]
      3.2 +/- 0.6, n = 53; control subjects 1.56 +/- 0.34, n = 102) using direct
      sequencing. Whereas no novel mutations were found in these genes, gene-dosage
      effects were found on fasting insulin for the Gly972Arg IRS-1 variant and on 2-h
      plasma glucose for the Gly1057Asp IRS-2 variant. The Gly972Arg IRS-1 variant was
      more prevalent in insulin-resistant patients compared with non-insulin-resistant
      individuals or control subjects (39.3 vs. 4.0 and 16.6%, P < 0.0031,
      respectively). A multivariate model that included BMI as a variable revealed
      significant effects of the Gly1057Asp IRS-2 variant on insulin resistance (P <
      0.016, odds ratio [OR] 7.2, 95% CI 1.29-43.3). HOMA(IR) was higher in carriers of
      both IRS variants than in those with IRS-2 mutations only or those with wild-type
      variants (6.2 +/- 2.3, 2.8 +/- 0.5, and 1.8 +/- 0.2, respectively; P < 0.01), and
      it was significantly associated with this genotype (P < 0.0085, OR 1.7, 95% CI
      1.09-2.99). We conclude that polymorphic alleles of both IRS-1 and IRS-2, alone
      or in combination, may have a functional impact on the insulin-resistant
      component of PCOS.

PMID- 11522687
TI  - Association of a novel point mutation (C159G) of the CTLA4 gene with type 1
      diabetes in West Africans but not in Chinese.
AB  - Here, we report on the detection of a novel point mutation of the CTLA4 gene at
      nucleotide position 159 (C-->G) leading to amino acid substitution at position 53
      (I-->M), as well as its association with type 1 diabetes in two ethnically
      distinct populations. Subjects included 182 unrelated type 1 diabetes children
      and 201 control subjects from Ghana, West Africa. The Chinese study population
      consisted of 350 type 1 diabetic children and 420 healthy control subjects from
      central China. Polymerase chain reaction-single-strand conformation polymorphism
      and sequence analysis were used to screen for polymorphisms in the CTLA4 gene.
      CTLA4 49 (A-->G) mutation conferred a risk of type 1 diabetes in the Chinese
      children (odds ratio 1.78, 95% CI 1.58-2.0), but not in the West African children
      (1.17, 0.84-1.64). On the other hand, the novel CTLA4 159 (C-->G) mutation
      conferred a risk of type 1 diabetes in the West African children (2.1, 1.54
      2.86), but not in the Chinese type 1 diabetic children. The novel CTLA4 gene
      polymorphism at nucleotide position 159 significantly associated with type 1
      diabetes in West Africans, but not in Chinese. On the other hand, the CTLA4 gene
      polymorphism at nucleotide position 49 significantly associated with type 1
      diabetes in Chinese, but not in West Africans.

PMID- 11522688
TI  - Genetic variation in the peroxisome proliferator-activated receptor-gamma2 gene
      (Pro12Ala) affects metabolic responses to weight loss and subsequent weight
      regain.
AB  - This study determined the effects of the peroxisome proliferator-activated
      receptor (PPAR)-gamma2 Pro12Ala variant on body composition and metabolism and
      the magnitude of weight regain in 70 postmenopausal women (BMI 25-40 kg/m(2)) who
      completed 6 months of a hypocaloric diet. At baseline, BMI, percent body fat,
      intra-abdominal and subcutaneous abdominal fat areas, resting metabolic rate,
      substrate oxidation, and postprandial glucose and insulin responses were not
      different between genotypes (Pro/Pro = 56, Pro/Ala and Ala/Ala = 14). The
      intervention similarly decreased body weight by 8 +/- 1% in women homozygous for
      the Pro allele and by 7 +/- 1% in women with the Ala allele (P < 0.0001). Fat
      oxidation did not change in Pro/Pro women but decreased 19 +/- 9% in women with
      the Ala allele (P < 0.05). Changes in glucose area were not different between
      groups; however, women with the Ala allele decreased their insulin area more than
      women homozygous for the Pro allele (P < 0.05). Weight regain during follow-up
      was greater in women with the Ala allele than women homozygous for the Pro allele
      (5.4 +/- 0.9 vs. 2.8 +/- 0.4 kg, P < 0.01). PPAR-gamma2 genotype was the best
      predictor of weight regain (r = 0.50, P < 0.01), followed by the change in fat
      oxidation (partial r = 0.35, P < 0.05; cumulative r = 0.58). Thus, the Pro12Ala
      variant of the PPAR-gamma2 gene may influence susceptibility for obesity.

PMID- 11522689
TI  - Young adults with diabetes: need for a new treatment paradigm.

PMID- 11522690
TI  - Organizing diabetes care: identify, monitor, prioritize, intensify.

PMID- 11522691
TI  - Can diabetes be prevented by vegetable fat?

PMID- 11522692
TI  - Noninvasive assessment of the diabetic patient for coronary artery disease.

PMID- 11522693
TI  - Characteristics of an adult population with newly diagnosed type 2 diabetes: the
      relation of obesity and age of onset.
AB  - OBJECTIVE: To determine whether adults diagnosed with type 2 diabetes at 18-44
      years of age (early type 2 diabetes) have different metabolic profiles at
      diagnosis than adults diagnosed at > or =45 years of age (usual type 2 diabetes).
      RESEARCH DESIGN AND METHODS: Within a health maintenance organization, we studied
      characteristics among 2,437 adults newly diagnosed with type 2 diabetes between
      1996 and 1998 who had measured weight, HbA(1c), blood pressure, and cholesterol
      within 3 months of diagnosis. We abstracted clinical data from electronic medical
      records. We compared mean and proportional differences with parametric t tests
      and chi(2) analyses, respectively. We used multiple logistic regression to
      identify the factors independently associated with the onset group (early vs.
      usual type 2 diabetes). RESULTS: There was an inverse linear relationship between
      BMI and age at diagnosis of type 2 diabetes (P < 0.001). On univariate analysis,
      adults with early type 2 diabetes were more obese (BMI 39 vs. 33 kg/m(2), P <
      0.001), were more likely to be female (P = 0.04), had slightly worse glycemic
      control (HbA(1c) 7.7 vs. 7.5%, P = 0.03), had a higher prevalence of diastolic
      hypertension (37 vs. 26%, P < 0.001), despite a lower prevalence of systolic
      hypertension (34 vs. 55%, P < 0.001), and had an equally high rate of abnormal
      lipids (82 vs. 78%, P = 0.13) than adults with usual type 2 diabetes. BMI, female
      gender, cholesterol, and diastolic and systolic blood pressure remained
      independently associated with onset group at multivariate analysis. CONCLUSIONS:
      Although both onset groups were on average obese, the inverse linear relationship
      of obesity and age of diabetes onset that we observed suggests that obesity is a
      continuous risk rather than a threshold risk for diabetes onset. Both onset
      groups had a high prevalence of cardiovascular disease risk factors.

PMID- 11522694
TI  - Dietary fat and incidence of type 2 diabetes in older Iowa women.
AB  - OBJECTIVE: To examine the associations between reported intakes of dietary fat
      and incident type 2 diabetes. RESEARCH DESIGN AND METHODS: We studied the
      relation between dietary fatty acids and diabetes in a prospective cohort study
      of 35,988 older women who initially did not have diabetes. Diet was assessed with
      a food frequency questionnaire at baseline, and 1,890 incident cases of diabetes
      occurred during 11 years of follow-up. RESULTS: After adjusting for age, smoking,
      alcohol consumption, BMI, waist-to-hip ratio, physical activity, demographic
      factors, and dietary magnesium and cereal fiber, diabetes incidence was
      negatively associated with dietary polyunsaturated fatty acids, vegetable fat,
      and trans fatty acids and positively associated with omega-3 fatty acids,
      cholesterol, and the Keys score. After simultaneous adjustment for other dietary
      fat, only vegetable fat remained clearly related to diabetes risk. Relative risks
      across quintiles of vegetable fat intake were 1.00, 0.90, 0.87, 0.84, and 0.82 (P
      = 0.02). Diabetes risk was also inversely related to substituting polyunsaturated
      fatty acids for saturated fatty acids and positively correlated to the Keys
      dietary score. CONCLUSIONS: These data support an inverse relation between
      incident type 2 diabetes and vegetable fat and substituting polyunsaturated fatty
      acids for saturated fatty acids and cholesterol.

PMID- 11522695
TI  - Clinical and psychological course of diabetes from adolescence to young
      adulthood: a longitudinal cohort study.
AB  - OBJECTIVE: To determine the clinical and psychological course of diabetes through
      adolescence and the relationship with glycemic control in young adulthood.
      RESEARCH DESIGN AND METHODS: A longitudinal cohort study of adolescents recruited
      from the register of the outpatient pediatric diabetes clinic. A total of 76
      individuals (43 male patients, 33 female patients) aged 11-18 years completed
      baseline assessments, and 65 individuals (86%) were reinterviewed as young adults
      (20-28 years of age). Longitudinal assessments were made of glycemic control
      (HbA(1c)), weight gain (BMI), and development of complications. Adolescents
      completed self-report questionnaires to assess emotional and behavioral problems
      as well as self-esteem. As young adults, psychological state was assessed by the
      Revised Clinical Interview Schedule and the self-report Brief Symptom Inventory.
      RESULTS: Mean HbA(1c) levels peaked in late adolescence and were worse in female
      participants (average 11.1% at 18-19 years of age). The proportion of individuals
      who were overweight (BMI >25.0 kg/m(2)) increased during the 8-year period from
      21 to 54% in female patients and from 2 to 28% in male patients. Serious diabetes
      related events included death in one patient and cognitive impairment in two
      patients. Individuals in whom diabetic complications developed (25% of male
      patients and 38% of female patients) had significantly higher mean HbA(1c) levels
      than those without complications (difference 1.9%, 95% CI 1.1-2.7, P < 0.0001).
      Behavioral problems at baseline were related to higher mean HbA(1c) during the
      subsequent 8 years (beta = 0.15, SEM (beta) 0.04, P < 0.001, 95% CI 0.07-0.24).
      CONCLUSIONS: The outcome for this cohort was generally poor. Behavioral problems
      in adolescence seem to be important in influencing later glycemic control.

PMID- 11522696
TI  - Neuropsychological profiles of children with type 1 diabetes 6 years after
      disease onset.
AB  - OBJECTIVE: To describe neuropsychological profiles and their relationship to
      metabolic control in children with type 1 diabetes 6 years after the onset of
      disease. RESEARCH DESIGN AND METHODS: Children with type 1 diabetes (n = 90),
      aged 6-17 years, who had previously been assessed soon after diagnosis and 2
      years later, were reevaluated 6 years after the onset of disease. Their
      neuropsychological profiles were compared with those of individuals in a
      community control group (n = 84), who had been assessed at similar intervals.
      Relationships between illness variables, such as age at the onset of disease and
      metabolic control history, and neuropsychological status were also examined.
      RESULTS: Six years after onset of disease, children with type 1 diabetes
      performed more poorly than control subjects on measures of intelligence,
      attention, processing speed, long-term memory, and executive skills. Attention,
      processing speed, and executive skills were particularly affected in children
      with onset of disease before 4 years of age, whereas severe hypoglycemia was
      associated with lower verbal and full-scale intelligence quotient scores.
      CONCLUSIONS: Neuropsychological profiles of children with type 1 diabetes 6 years
      after the onset of disease are consistent with subtle compromise of anterior and
      medial temporal brain regions. Severe hypoglycemia, particularly in very young
      children, is the most plausible explanation for neuropsychological deficits, but
      the contributory role of chronic hyperglycemia warrants further exploration.

PMID- 11522697
TI  - Developing a prediction rule from automated clinical databases to identify high
      risk patients in a large population with diabetes.
AB  - OBJECTIVE: To develop and validate a prediction rule for identifying diabetic
      patients at high short-term risk of complications using automated data in a large
      managed care organization. RESEARCH DESIGN AND METHODS: Retrospective cohort
      analyses were performed in 57,722 diabetic members of Kaiser Permanente, Northern
      California, aged > or =19 years. Data from 1994 to 1995 were used to model risk
      for macro- and microvascular complications (n = 3,977), infectious complications
      (n = 1,580), and metabolic complications (n = 316) during 1996. Candidate
      predictors (n = 36) included prior inpatient and outpatient diagnoses, laboratory
      records, pharmacy records, utilization records, and survey data. Using split
      sample validation, the risk scores derived from logistic regression models in
      half of the population were evaluated in the second half. Sensitivity, positive
      predictive value, and receiver operating characteristics curves were used to
      compare scores obtained from full models to those derived using simpler
      approaches. RESULTS: History of prior complications or related outpatient
      diagnoses were the strongest predictors in each complications set. For patients
      without previous events, treatment with insulin alone, serum creatinine > or =1.3
      mg/dl, use of two or more antihypertensive medications, HbA(1c) >10%, and
      albuminuria/microalbuminuria were independent predictors of two or all three
      complications. Several risk scores derived from multivariate models were more
      efficient than simply targeting patients with elevated HbA(1c) levels for
      identifying high-risk patients. CONCLUSIONS: Simple prediction rules based on
      automated clinical data are useful in planning care management for populations
      with diabetes.

PMID- 11522698
TI  - Treatment satisfaction with inhaled insulin in patients with type 1 diabetes: a
      randomized controlled trial.
AB  - OBJECTIVE: In patients with type 1 diabetes, glycemic control can be achieved as
      effectively with an inhaled insulin regimen, comprising preprandial inhaled
      intrapulmonary insulin plus a bedtime ultralente injection, as with a
      conventional subcutaneous insulin regimen involving two to three injections per
      day. Our objective was to compare patient satisfaction between inhaled insulin
      and subcutaneous insulin. RESEARCH DESIGN AND METHODS: Subjects with type 1
      diabetes participated in a 12-week open-label trial and were randomized to either
      an inhaled insulin regimen or a subcutaneous insulin regimen. Subjects (n = 69)
      were asked to complete a 15-item self-administered satisfaction questionnaire,
      the Patient Satisfaction with Insulin Therapy (PSIT) Questionnaire, at baseline
      and week 12. Outcomes included mean percentage changes in global (overall)
      satisfaction and two subscales: convenience/ease of use and social comfort.
      RESULTS: The mean percentage improvement in overall satisfaction with inhaled
      insulin (35.1%, 95% CI 18.0-52.2) was greater than with subcutaneous insulin
      (10.6%, 4.7-16.5) (P < 0.01), as was the improvement in convenience/ease of use:
      inhaled insulin 41.3% (22.9-59.6) versus subcutaneous insulin 11.2% (4.1-18.3; P
      < 0.01). Improvement in social comfort was greater with inhaled insulin but was
      not statistically significant. The 12-week change in HbA(1c) was associated with
      improved overall satisfaction (r = -0.27, P = 0.04). CONCLUSIONS: Inhaled insulin
      may offer the first practical, noninvasive alternative to insulin injections. For
      patients with type 1 diabetes, inhaled insulin maintains glycemic control and
      provides greater overall satisfaction and convenience/ease of use than
      subcutaneous insulin.

PMID- 11522699
TI  - Does microalbuminuria predict diabetic nephropathy?
AB  - OBJECTIVE: To describe risk factors associated with microalbuminuria (MA) in
      subjects with diabetes, investigate the predictive value of MA as a marker of
      risk for diabetic nephropathy (DN), and define risk factors associated with the
      development and progression of MA. RESEARCH DESIGN AND METHODS: We conducted a
      prospective longitudinal study of 23 diabetic subjects with persistent MA and 209
      diabetic subjects without MA who attended diabetes clinics at the University of
      Michigan Medical Center in 1989 and 1990. Both groups were examined at baseline
      and after 7 years. At baseline, urinary albumin-to-creatinine ratios were studied
      in random, first morning, and 24-h urine samples. At follow-up, a 12-h overnight
      urine sample was collected and analyzed for albumin and creatinine. At baseline,
      MA was defined by at least two separate urine specimens with albumin-to
      creatinine ratios between 30 and 299 microg albumin per milligram of creatinine.
      RESULTS: MA regressed in 56% of subjects with baseline MA without systematic
      application of corrective measures and developed in 16% of subjects without
      baseline MA. The predictive value positive of MA as a marker of risk for DN was
      43%, and the predictive value negative was 77%. In the combined cohort, the
      incidence and progression of MA were significantly associated with poor glycemic
      control and duration of diabetes between 10 and 14 years. CONCLUSIONS: MA may not
      be as sensitive and specific a predictor of DN as previously suggested. Other
      markers of risk for DN are needed for optimal clinical management.

PMID- 11522700
TI  - A biethnic community survey of cognition in participants with type 2 diabetes,
      impaired glucose tolerance, and normal glucose tolerance: the New Mexico Elder
      Health Survey.
AB  - OBJECTIVE: To determine whether elderly individuals with type 2 diabetes or
      impaired glucose tolerance are at increased risk for cognitive impairment
      compared with individuals with normal glucose tolerance. RESEARCH DESIGN AND
      METHODS: Elderly Hispanic individuals (n = 414) and non-Hispanic white
      individuals (n = 469) aged > or =65 years, randomly selected from the Medicare
      rolls of Bernalillo County (Albuquerque), NM, were recruited for an
      interview/examination that included an evaluation of glucose tolerance.
      Information on nine tests of cognitive function and two measures of depression
      allowed comparisons between diabetic status and these functions. Comparisons also
      were made between glycosolated hemoglobin concentrations and these cognitive
      tests in the 188 participants with diabetes. RESULTS: None of the mean scores on
      the tests of cognitive function was significantly lower in the participants with
      diabetes compared with those participants with normal glucose tolerance after
      adjustments for ethnicity, sex, age, level of education, and presence of
      depression, with or without elimination of those with dementia (Mini-Mental State
      Exam <18). Interestingly, participants with impaired glucose tolerance tended to
      score higher than those with normal glucose tolerance. No significant
      associations were found between glycosolated hemoglobin concentrations and
      cognitive test scores in participants with diabetes. CONCLUSIONS: We could not
      show any increased risk for cognitive impairment in participants with diabetes
      compared with those with normal glucose tolerance after adjustments for
      ethnicity, sex, age, education, and presence of depression, before or after
      elimination of dementia in this random sample from a biethnic population of
      predominantly community-dwelling elders.

PMID- 11522701
TI  - Elevated incidence of type 2 diabetes in San Antonio, Texas, compared with that
      of Mexico City, Mexico.
AB  - OBJECTIVE: To compare the incidence of type 2 diabetes between low-income Mexican
      Americans residing in San Antonio, Texas, and low-income residents in Mexico
      City, Mexico. RESEARCH DESIGN AND METHODS: Using data from the San Antonio Heart
      Study and the Mexico City Diabetes Study, we compared the incidence of type 2
      diabetes in 35- to 64-year-old low-income Mexican-American residents of San
      Antonio with similarly aged low-income residents of Mexico City. Because of the
      different follow-up times in the two studies, Poisson regression was used to
      compare the rates of diabetes. Potential risk factors for diabetes were also
      analyzed to determine whether they explained or contributed to a difference in
      incidence. RESULTS: The age- and sex-adjusted incidence of type 2 diabetes was
      significantly higher in San Antonio (RR 2.01) compared with Mexico City. This
      difference was seen primarily in the oldest age group (55-64 years of age) and
      remained statistically significant after adjusting for a number of diabetes risk
      factors, including demographic, anthropometric, and metabolic variables. Follow
      up rates were similar in both cities. CONCLUSIONS: We conclude that there was a
      higher incidence of type 2 diabetes in San Antonio than in Mexico City, and that
      difference occurred primarily in individuals in the oldest age group. The
      potential mediating factors we examined did not account for this difference.
      Other factors, such as exercise and diet, which were not available for analysis
      in this study, in addition to a cohort effect, may have contributed to the
      difference in incidence of type 2 diabetes in the two cities. In addition, there
      was no evidence of a higher case fatality among diabetic individuals from Mexico
      City compared with San Antonio.

PMID- 11522702
TI  - Genotype Arg/Arg, but not Trp/Arg, of the Trp64Arg polymorphism of the beta(3)
      adrenergic receptor is associated with type 2 diabetes and obesity in a large
      Japanese sample.
AB  - OBJECTIVE: Despite a large number of studies, no association of the Trp64Arg
      polymorphism of the beta(3)-adrenergic receptor gene with obesity and type 2
      diabetes has yet to be clearly elucidated. We examined the associations in a
      large population-based sample. RESEARCH DESIGN AND METHODS: A total of 1,685
      subjects (935 women and 750 men, aged 58.7 +/- 12.4 years) from a cohort
      population (n = 3,706) of the Funagata Diabetes Study were divided into three
      groups according to genotypes: Trp/Trp (n = 1,155), Trp/Arg (n = 486), and
      Arg/Arg (n = 44). Glucose tolerance was diagnosed according to the 1985 World
      Health Organization criteria. Subjects who had a BMI > or =30 kg/m(2) were
      considered obese. Associations with the traits related to obesity, diabetes,
      hypertension, and dyslipidemia were also examined. The chi(2) test and analysis
      of variance were used for the association studies and to assess the differences
      in the traits' values, respectively. RESULTS: More subjects with genotype Arg/Arg
      were obese and had diabetes (13.6% for each) than those with genotype Trp/Trp
      (3.29%, P < 0.001; and 4.16%, P = 0.007, respectively) or genotype Trp/Arg
      (2.06%, P < 0.001; and 5.97%, P = 0.051, respectively). No significant
      differences in the frequencies of occurrence of these conditions were observed
      between genotypes Trp/Arg and Trp/Trp. Traits related to obesity, such as percent
      body fat (28.82 +/- 7.95 vs. 25.93 +/- 7.21, P = 0.038) and BMI (25.07 +/- 3.84
      vs. 23.63 +/- 3.18, P = 0.018), were higher in the genotype Arg/Arg than in the
      genotype Trp/Trp groups. CONCLUSIONS: Genotype Arg/Arg, but not Trp/Arg, of the
      beta(3)-adrenergic receptor was associated with both obesity and type 2 diabetes
      in a large Japanese sample.

PMID- 11522703
TI  - Temporal trends in BMI among adults with diabetes.
AB  - OBJECTIVE: Increasing obesity within the general population has been accompanied
      by rising rates of diabetes. The extent to which obesity has increased among
      people with diabetes is unknown, as are the potential consequences for diabetes
      outcomes. RESEARCH DESIGN AND METHODS: Community medical records (hospital and
      ambulatory) of all Rochester, Minnesota, residents aged > or =30 years who first
      met standardized research criteria for diabetes from 1970 to 1989 (n = 1,306)
      were reviewed to obtain data on BMI and related characteristics as of the
      diabetes identification date (+/-3 months). Vital status as of 31 December 1999
      and date of death for those who died were obtained from medical records, State of
      Minnesota death tapes, and active follow-up. RESULTS: As of the identification
      date, data on BMI were available for 1,290 cases. Of the 272 who first met
      diabetes criteria in 1970-1974, 33% were obese (BMI > or =30), including 5% who
      were extremely obese (BMI > or =40). These proportions increased to 49% (P <
      0.001) and 9% (P = 0.012), respectively, for the 426 residents who first met
      diabetes criteria in 1985-1989. BMI increased significantly with increasing
      calendar year of diabetes identification in multivariable regression analysis.
      Analysis of survival revealed an increased hazard of mortality for BMI > or =41,
      relative to BMI of 23-25 (hazard ratio 1.60, 95% CI 1.09-2.34, P = 0.016).
      CONCLUSIONS: The prevalence of obesity and extreme obesity among individuals at
      the time they first met criteria for diabetes has increased over time. This is
      disturbing in light of the finding that diabetic individuals who are extremely
      obese are at increased risk of mortality compared with their nonobese diabetic
      counterparts.

PMID- 11522704
TI  - Smoking as a modifiable risk factor for type 2 diabetes in middle-aged men.
AB  - OBJECTIVE: To examine the effects of cigarette smoking, giving up smoking, and
      primary or secondary pipe or cigar smoking on the risk of type 2 diabetes.
      RESEARCH DESIGN AND METHODS: A prospective study followed 7,735 men aged 40-59
      years from general practices in 24 British towns for an average of 16.8 years.
      Incident cases of physician-diagnosed diabetes were ascertained by repeated
      postal questionnaires and systematic reviews of primary care records. RESULTS: A
      total of 290 incident cases of diabetes were found in 7,124 men with no history
      of diabetes, coronary heart disease, or stroke. Cigarette smoking was associated
      with a significant increase in risk of diabetes, even after adjustment for age,
      BMI, and other potential confounders. The benefit of giving up smoking was only
      apparent after 5 years of smoking cessation, and risk reverted to that of never
      smokers only after 20 years. The risk of diabetes in those who switched from
      smoking cigarettes to pipe or cigars remained equal to the risk in continuing
      cigarette smokers. Men who gave up smoking during the first 5 years of follow-up
      showed significant weight gain and subsequently higher risk of diabetes than
      continuing smokers. CONCLUSIONS: Cigarette smoking is an independent and
      modifiable risk factor for type 2 diabetes. Smoking cessation is associated with
      weight gain and a subsequent increase in risk of diabetes, but in the long term,
      the benefits of giving up smoking outweigh the adverse effects of early weight
      gain.

PMID- 11522705
TI  - Stress echocardiography for risk stratification of diabetic patients with known
      or suspected coronary artery disease.
AB  - OBJECTIVE: Coronary artery disease (CAD) is a leading cause of mortality and
      morbidity in diabetic patients; therefore, their risk stratification is a
      relevant issue. Because exercise tolerance is frequently impaired in these
      patients, pharmacological stress echocardiography (SE) has been suggested as a
      valuable alternative. Our aim was to evaluate the prognostic value of this
      technique in diabetic patients with known or suspected CAD. RESEARCH DESIGN AND
      METHODS: A total of 259 consecutive diabetic patients underwent pharmacological
      SE (dobutamine in 108 patients and dipyridamole in 151 patients) and follow-up
      for 24 +/- 22 months. A comparison between the prognostic value of SE and
      exercise electrocardiography (ECG) was made in a subgroup of 120 subjects.
      RESULTS: A total of 13 cardiac deaths and 13 nonfatal infarctions occurred during
      follow-up, and 58 patients were revascularized. Univariate predictors of outcome
      were known CAD, positive SE, rest and peak wall motion score index (WMSI), and
      peak/rest WMSI variation. Peak WMSI was the only significant and independent
      prognostic indicator (odds ratio 11; 95% CI 4-29, P < 0.0001) on multivariate
      Cox's analysis. After adjustment for the most predictive clinical and exercise
      ECG variables, SE provided 43% additional prognostic information (gain in X(2) =
      7, P < 0.01). Moreover, positive SE was associated with a significantly lower
      event-free survival. CONCLUSIONS: SE effectively predicts cardiac events in
      diabetic patients with known or suspected CAD and adds additional prognostic
      information as compared with exercise ECG.

PMID- 11522706
TI  - Clinically useful estimates of insulin sensitivity during pregnancy: validation
      studies in women with normal glucose tolerance and gestational diabetes mellitus.
AB  - OBJECTIVE: We examined whether selected indexes of insulin sensitivity derived
      from an oral glucose tolerance test (IS(OGTT)) or fasting glucose/insulin levels
      (IS(QUICKI) and IS(HOMA)) can be used to predict insulin sensitivity in women
      before and during pregnancy. RESEARCH DESIGN AND METHODS: A 2-h euglycemic
      hyperinsulinemic clamp (5 mmol/l glucose, 40 mU. m(-2). min(-1) insulin) and a
      120-min oral glucose tolerance test (75 g load pregravid, 100 g pregnant) were
      repeated on 15 women (10 with normal glucose tolerance [NGT] and 5 with
      gestational diabetes mellitus [GDM]) pregravid and during both early (12-14
      weeks) and late (34-36 weeks) pregnancy. An index of insulin sensitivity derived
      from the clamp (IS(CLAMP)) was obtained from glucose infusion rates adjusted for
      change in fat-free mass and endogenous glucose production measured using [6,6(
      2)H(2)]glucose. RESULTS: Univariate analysis using combined groups and periods of
      pregnancy resulted in significant correlations between IS(CLAMP) and IS(OGTT)
      (r(2) = 0.74, P < 0.0001), IS(QUICKI) (r(2) = 0.64, P < 0.0001), and IS(HOMA)
      (r(2) = 0.53, P < 0.0001). The IS(OGTT) provided a significantly better
      correlation (P < 0.0001) than either IS(QUICKI) or IS(HOMA.) Multivariate
      analysis showed a significant group effect (P < 0.0003) on the prediction model,
      and separate equations were developed for the NGT (r(2) = 0.64, P < 0.0001) and
      GDM (r(2) = 0.85, P < 0.0001) groups. When subdivided by period of pregnancy, the
      correlation between IS(CLAMP) and IS(OGTT) pregravid was r(2) = 0.63 (P =
      0.0002), during early pregnancy was r(2) = 0.80 (P < 0.0001), and during late
      pregnancy was r(2) = 0.64 (P = 0.0002). CONCLUSIONS: Estimates of insulin
      sensitivity from the IS(OGTT) during pregnancy were significantly better than
      from fasting glucose and insulin values. However, separate prediction equations
      are necessary for pregnant women with NGT and women with GDM.

PMID- 11522707
TI  - Total antioxidant status and coronary artery calcification in type 1 diabetes.
AB  - OBJECTIVE: Type 1 diabetes is associated with a high risk of coronary heart
      disease (CHD), despite the absence of dyslipidemia. Oxidative modification may
      render LDLs more atherogenic. We aimed to assess antioxidant status in type 1
      diabetes and its association with coronary artery calcification (CAC). RESEARCH
      DESIGN AND METHODS: Total antioxidant status (TAS) of serum was measured using
      the Trolox equivalent antioxidant capacity assay in 48 type 1 diabetic and 25
      nondiabetic subjects. The presence of CAC was assessed in the diabetic subjects
      using electron beam computed tomography. RESULTS: TAS was reduced in type 1
      diabetic subjects compared with nondiabetic subjects (Mann-Whitney U test, P <
      0.0001). There were associations between TAS and HbA(1c) (r = -0.43; P = 0.0026)
      and duration of diabetes (r = -0.35; P = 0.0157). Significant CAC was considered
      present if the Agatston score was >10. The diabetic subjects with significant CAC
      were older (P < 0.0001); had longer duration of diabetes (P = 0.0002); were more
      likely to have high blood pressure (P = 0.040); had higher total cholesterol
      concentration (P = 0.039), serum creatinine concentration (P = 0.003), and
      urinary albumin-to-creatinine ratio (P = 0.022); and had lower serum TAS (P =
      0.018) compared with those without significant calcification. In logistic
      regression with CAC as the dependent variable, TAS was entered as a predictor,
      and the effects on its predictive value of adding other explanatory variables in
      bivariate analyses were assessed. The power of TAS to predict CAC was independent
      of many of the traditional CHD risk factors. Whereas TAS as a predictor was no
      longer statistically significant when age or duration of diabetes were entered
      into the model, the odds ratio for a TAS concentration above the median value
      predicting significant CAC only increased from 0.19 to 0.26 and 0.32,
      respectively. CONCLUSIONS: TAS is reduced in type 1 diabetes and is associated
      with the presence of CAC.

PMID- 11522708
TI  - Congestive heart failure in type 2 diabetes: prevalence, incidence, and risk
      factors.
AB  - OBJECTIVE: To estimate the prevalence and incidence of congestive heart failure
      (CHF) in populations with and without type 2 diabetes and to identify risk
      factors for diabetes-associated CHF. RESEARCH DESIGN AND METHODS: We searched the
      inpatient and outpatient electronic medical records of 9,591 individuals
      diagnosed with type 2 diabetes before 1 January 1997 and those of an age- and sex
      matched control group without diabetes for a diagnosis of CHF. Among those
      without a baseline diagnosis of CHF, we searched forward for 30 months for
      incident cases of CHF. We constructed multiple logistic regression models to
      identify risk factors for both prevalent and incident CHF. RESULTS: CHF was
      prevalent in 11.8% (n = 1,131) of diabetic subjects and 4.5% (n = 435) of control
      subjects at baseline. We observed incident cases of CHF in 7.7% of diabetic
      subjects free of CHF at baseline (650 of 8,460) and in 3.4% of control subjects
      (314 of 9,156). In diabetic subjects, age, diabetes duration, insulin use,
      ischemic heart disease, and elevated serum creatinine were independent risk
      factors for both prevalent and incident CHF. Better glycemic control at baseline,
      and improved glycemic and blood pressure control at follow-up predicted the
      development of CHF. CONCLUSIONS: Despite controlling for age, duration of
      diabetes, presence of ischemic heart disease, and presence of hypertension,
      insulin use was associated with both prevalent and incident CHF. Why insulin use
      and better glycemic control both at baseline and follow-up independently
      predicted CHF deserves further study.

PMID- 11522709
TI  - Advanced glycation end products in nondiabetic patients with coronary artery
      disease.
AB  - OBJECTIVE: To investigate whether advanced glycation end products (AGEs)
      participate in the development of coronary artery disease (CAD) in nondiabetic
      and diabetic subjects. RESEARCH DESIGN AND METHODS: Serum concentrations of AGEs
      were measured using a newly established enzyme-linked immunosorbent assay in 48
      nondiabetic patients (normal glucose tolerance, n = 20; impaired glucose
      tolerance, n = 28) who received coronary angiography for the study of chest pain
      or suspected CAD. Insulin sensitivity was examined by the euglycemic
      hyperinsulinemic glucose clamp technique and was estimated as the mean glucose
      infusion rate during the last 30 min of clamp time (M value). RESULTS: Patients
      were classified into four groups based on the number of significantly stenosed
      vessels, defined as 0-, 1-, 2-, or 3-vessel disease. Serum concentrations of AGEs
      were significantly higher in nondiabetic subjects with CAD than in control
      subjects (2.42 +/- 0.65 vs. 1.96 +/- 0.40 mU/ml, P < 0.01) and significantly
      correlated with the number of significantly stenosed vessels (r = 0.678, P <
      0.001). M values significantly inversely correlated with serum concentrations of
      AGEs (r = -0.490, P < 0.05). In multiple regression analysis, with the number of
      significantly stenosed vessels as the dependent variable, serum concentrations of
      AGEs, 2-h plasma glucose, and areas under the plasma glucose response curve were
      independently associated. CONCLUSIONS: This pilot study indicates the relation
      between AGEs and the severity of CAD in nondiabetic patients. The measurement of
      serum AGE concentrations may be predictive of vascular damage.

PMID- 11522710
TI  - Variations of ambulatory blood pressure with position in patients with type 1
      diabetes: influence of disease duration and microangiopathy in a pilot study.
AB  - OBJECTIVE: To study the influence of position changes on 24-h ambulatory blood
      pressure (ABP) in normotensive or mildly hypertensive normoalbuminuric patients
      with type 1 diabetes. RESEARCH DESIGN AND METHODS: A cross-sectional evaluation
      of patients was staged according to the duration of diabetes (DD) and the
      presence of microangiopathy. We recruited 37 patients (30 men and 7 women), aged
      38 +/- 12 years, who were normotensive or mildly hypertensive (diastolic blood
      pressure [DBP] <105 mmHg) and free of antihypertensive treatment and
      microalbuminuria. They were included according to DD (group 1, <5 years; group 2,
      > or =10 years). An additional group of seven diabetic patients with
      microalbuminuria and mild untreated hypertension was also investigated. We
      recorded 24-h ambulatory blood pressure every 15 min with a position sensor,
      which allowed for the discrimination between standing or supine/sitting position
      in the patient. RESULTS: Mean daytime (10:00 A.M. to 8:00 P.M.) ABP in
      supine/sitting position did not significantly differ between groups 1 and 2.
      However, standing ambulatory systolic blood pressure (ASBP) and ambulatory DBP
      (ADBP) were significantly higher than supine/sitting ASBP and ADBP in group 1
      (DeltaSBP 4 +/- 5, DeltaDPB 4 +/- 6 mmHg, P < 0.01) but not in group 2 (DeltaSBP
      2 +/- 8, DeltaDBP 2 +/- 4 mmHg, P = NS). Patients free of microangiopathy
      presented with significantly higher ABP in standing position than in
      sitting/lying position, whereas patients with retinopathy and/or nephropathy
      exhibited no significant increase of ABP during standing. CONCLUSION: The
      monitoring of position during ambulatory measurement of blood pressure in type 1
      diabetic patients shows different patterns in relation to disease duration and
      the presence of microangiopathy.

PMID- 11522711
TI  - Insulin resistance syndrome predicts coronary heart disease events in elderly
      type 2 diabetic men.
AB  - OBJECTIVE: To investigate whether cardiovascular risk factors cluster with
      hyperinsulinemia in elderly type 2 diabetic subjects and, if so, whether this
      clustering predicts coronary heart disease (CHD) events during a 7-year follow
      up. RESEARCH DESIGN AND METHODS: Clustering of cardiovascular risk factors was
      analyzed by factor analysis. Cox regression models were used to investigate
      whether these clusters (factors) predict CHD events (CHD death or nonfatal
      myocardial infarction) during a 7-year follow-up in 229 type 2 diabetic subjects
      aged 65-74 years. RESULTS: There were 70 CHD events (21 in men and 49 in women)
      during the follow-up period. In diabetic men, components of the insulin
      resistance syndrome (IRS) loaded on Factor 1 (the insulin resistance factor),
      which reflected high fasting insulin, obesity (high BMI), central obesity (high
      waist-to-hip ratio), high total triglycerides, and a short duration of diabetes.
      Only this IRS factor predicted CHD events in multivariate Cox regression analysis
      (hazard ratio [HR] 1.71, 95% CI 1.08-2.71, P = 0.022). In diabetic women,
      components of IRS loaded on two factors, none of which predicted CHD events. In
      women, only Factor 4, characterized by advanced age, left ventricular hypertrophy
      on electrocardiogram, high alcohol consumption, high systolic blood pressure, and
      albuminuria, predicted CHD events in multivariate Cox regression analysis (1.34,
      1.03-1.74, P = 0.03). CONCLUSIONS: IRS is a risk factor for CHD in elderly type 2
      diabetic men.

PMID- 11522712
TI  - Admission plasma glucose: an independent risk factor in nondiabetic women after
      coronary artery bypass grafting.
AB  - OBJECTIVE: To investigate the relationship between admission plasma glucose and
      30-day mortality after primary isolated coronary artery bypass grafting (CABG) in
      nondiabetic patients. RESEARCH DESIGN AND METHODS: All nondiabetic patients with
      admission plasma glucose measurement undergoing primary isolated CABG from 1993
      to 1997 were included in this study. RESULTS: In 878 consecutive patients (155
      women), overall mortality was 3.4% (95% CI 2.3-4.8). The mortality rate in women
      (n = 11; 7.1%, 3.6-12.3) was higher than in men (n = 19; 2.6%, 1.6-4.1) (P =
      0.01). There was a positive correlation between plasma glucose and 30-day
      mortality among women only (P = 0.0001). There was a higher mortality rate in the
      upper two glucose quartiles (11.7%, 5.5-21.0) compared with the lower two
      quartiles (2.6%, 3.0-8.9) in the female patients (P = 0.03); a plasma glucose of
      6.0 mmol/l separated high- and low-mortality groups. Furthermore, women in the
      upper two glucose quartiles had a fourfold higher mortality rate than men in the
      similar quartiles (P = 0.002). Among men, there was no difference in mortality
      rate across glucose quartiles. In a multivariate analysis, admission plasma
      glucose, history of thyroid disease, left ventricular ejection fraction <0.35,
      operation bypass time, and perioperative myocardial infarction were independently
      associated with mortality. CONCLUSIONS: Women with admission plasma glucose < or
      =6.0 mmol/l and men across the whole range of glucose values had similar
      mortality rates after CABG. The surplus female mortality was found only in
      subjects with plasma glucose >6 mmol/l. Further studies are needed to appraise
      the possible influence of glucose status on outcome from CABG in nondiabetic
      subjects.

PMID- 11522713
TI  - Impaired incretin response after a mixed meal is associated with insulin
      resistance in nondiabetic men.
AB  - OBJECTIVE: To investigate whether features of the insulin resistance syndrome are
      associated with altered incretin responses to food intake. RESEARCH DESIGN AND
      METHODS: From a population-based study, 35 men were recruited, representing a
      wide spectrum of insulin sensitivity and body weight. Each subject underwent a
      hyperinsulinemic-euglycemic clamp to determine insulin sensitivity. A mixed meal
      was given, and plasma levels of gastric inhibitory polypeptide (GIP) and glucagon
      like peptide 1 (GLP-1), as well as insulin, glucagon, and glucose were measured.
      RESULTS: Insulin resistance was associated with impaired GIP and GLP-1 responses
      to a mixed meal. The total area under the curve (AUC) of the GIP response after
      the mixed meal was associated with insulin sensitivity (r = 0.54, P < 0.01).
      There was a significant difference between the highest and the lowest tertile of
      insulin sensitivity (P < 0.05). GLP-1 levels 15 min after food intake were
      significantly lower in the most insulin-resistant tertile compared with the most
      insulin-sensitive tertile. During the first hour, the AUC of GLP-1 correlated
      significantly with insulin sensitivity (r = 0.47, P < 0.01). Multiple linear
      regression analysis showed that insulin resistance, but not obesity, was an
      independent predictor of these decreased incretin responses. CONCLUSIONS: In
      insulin resistance, the GIP and GLP-1 responses to a mixed meal are impaired and
      are related to the degree of insulin resistance. Decreased incretin
      responsiveness may be of importance for the development of impaired glucose
      tolerance.

PMID- 11522714
TI  - The insertion/deletion polymorphism of the ACE gene is related to insulin
      sensitivity in overweight women.
AB  - OBJECTIVE: The ACE insertion/deletion (I/D) polymorphism has been identified as a
      genetic risk factor for coronary heart disease (CHD). The deletion (D) allele of
      the ACE gene may be associated with higher insulin sensitivity. Individuals who
      are homozygous for the DD allele have higher ACE levels and possibly more
      angiotensin II, which, when infused exogenously, causes an increase in insulin
      sensitivity. The purpose of this study was to investigate the association of the
      I/D polymorphism of the ACE gene with insulin sensitivity and CHD risk factors.
      RESEARCH DESIGN AND METHODS: The study included 66 women (ages 57 +/- 1 years)
      who were overweight or obese (means +/- SEM, BMI = 33 +/- 1 kg/m(2)) and
      sedentary (VO(2max) = 19.6 +/- 0.4 ml. kg(-1). min(1)). Total body fat mass and
      percent fat were determined by dual-energy X-ray absorptiometry, and abdominal
      fat was by computed tomography. Insulin sensitivity was measured during the last
      30 min of 3-h hyperinsulinemic-euglycemic clamps (40 mU. m(-2). min(-1)).
      Comparisons were made among women with the II (n = 9), ID (n = 36), and DD (n =
      21) genotypes. RESULTS: Age, percent body fat, waist-to-hip ratio, visceral and
      subcutaneous abdominal fat areas, plasma lipid levels, and systolic and diastolic
      blood pressures did not differ by ACE genotype. Fasting glucose and 2-h glucose
      levels were similar among genotypes, but fasting plasma insulin levels were lower
      in DD women than in ID women (P < 0.05). Glucose utilization was higher in women
      with the DD genotype than in women with the II genotype (53.1 +/- 3.9 vs. 36.0 +/
      3.8 micromol. kg(-1) FFM. min(-1), P = 0.01) and was higher in ID women than in
      II women (48.5 +/- 2.5 micromol. kg(-1) FFM. min(-1), P = 0.04). CONCLUSIONS:
      These data suggest that the I/D polymorphism is not associated with risk factors
      for CHD in overweight sedentary women; however, women who are homozygous for the
      D allele of the ACE gene are more insulin sensitive, whereas women who are
      homozygous for the I allele of the ACE gene have greater insulin resistance and
      potential risk for type 2 diabetes.

PMID- 11522715
TI  - Relations between ACE gene and ecNOS gene polymorphisms and resistive index in
      type 2 diabetic patients with nephropathy.
AB  - OBJECTIVE: ACE and endothelial cell nitric oxide synthase (ecNOS) genotypes have
      been reported to be related to the incidence of renal diseases and coronary
      artery diseases. In order to assess the effect of the gene polymorphism of both
      ACE and ecNOS on renal hemodynamic abnormality, we examined 155 Japanese patients
      with type 2 diabetes with various stages of nephropathy. RESEARCH DESIGN AND
      METHODS: The patients ranged in age from 40 to 72 years (92 men and 63 women).
      They were divided into four groups: group 1 consisted of patients with urinary
      albumin excretion (UAE) <30 mg/day (n = 69), group 2 had 30 < or = UAE < 300
      mg/day (n = 44), group 3 had UAE > or =300 mg/day and serum creatinine <1.5 mg/dl
      (n = 22), and group 4 had serum creatinine >1.5 mg/dl (n = 20). Intrarenal
      hemodynamics were studied by duplex Doppler sonography in patients with type 2
      diabetes. The ACE and ecNOS gene polymorphisms were examined by polymerase chain
      reaction. RESULTS: There were no significant differences in sex, BMI, and blood
      glucose level, but there were differences in HbA(1c) and lipoprotein profiles
      among the four groups. There were no significant differences in the distribution
      of ACE genotype or in the frequency of the ecNOS 4a allele among the four groups.
      Resistive index (RI) values of the interlobar arteries of group 4 were
      significantly higher than those of groups 1, 2, and 3, whereas the RI values were
      not significantly different among groups 1, 2, and 3. Multiple regression
      analysis showed that age, duration of diabetes, systolic and diastolic blood
      pressure, and creatinine clearance were significantly associated with the
      increased RI values, but that there was no significant association between RI
      values and the ecNOS genotype (R(2) = 0.613, P < 0.0001). CONCLUSIONS: These
      results suggest that intrarenal hemodynamic abnormalities are present as a
      feature of the progression of nephropathy in type 2 diabetes, and that they are
      associated with age, duration of diabetes, decreased creatinine clearance, and
      blood pressure, but not with the genetic factors of the ACE and ecNOS gene
      polymorphism in nephropathy of type 2 diabetes.

PMID- 11522716
TI  - Evidence of primary beta-cell destruction by T-cells and beta-cell
      differentiation from pancreatic ductal cells in diabetes associated with active
      autoimmune chronic pancreatitis.
AB  - OBJECTIVE: Diabetes associated with autoimmune chronic pancreatitis (ACP) is a
      subtype of diabetes that is responsive to corticosteroid treatment of progressive
      endocrine and exocrine dysfunction. However, little is known about pathological
      changes of islet and exocrine pancreas in ACP. RESEARCH DESIGN AND METHODS: We
      examined pancreatic specimens obtained on biopsy from four diabetic men with ACP
      (mean [range]: age 62 years [48-78], duration of ACP 3 months [1-5], duration of
      diabetes 1 month [0-3]) morphologically, immunohistochemically, and
      morphometrically. RESULTS: The pancreatic specimens in all cases exhibited
      inflammatory cell infiltration surrounding ductal cells and extensive fibrosis.
      Some islets were infiltrated with mononuclear cells with disrupted beta-cells.
      The subsets of T-cells infiltrated to the islets were mainly CD8(+). Islet beta
      cell volume was decreased; the mean percentage area of beta-cells in the islets
      in four cases with ACP were 16% (range 13-20) (P = 0.0015 vs. type 2 diabetic
      patients, 48% [27-73], n = 8; P = 0.0002 vs. nondiabetic control subjects, 58%
      [39-77], n = 7). Preserved ductal cells were surrounded predominantly by CD8(+)
      or CD4(+) T-cells. Some cytokeratin 19-positive ductal cells contained insulin
      and glucagon, representing upregulated differentiation of islet cells from ductal
      cells. Insulin promoter factor-1 (IPF-1) was hyperexpressed in insulin-containing
      ductal cells. CONCLUSIONS: Diabetes associated with ACP is caused by T-cell
      mediated mechanisms primarily involving islet beta-cells as well as pancreatic
      ductal cells. In ACP, ductal islet precursor cells were associated with IPF-1
      hyperexpression, suggesting a critical role of IPF-1 on islet cell
      differentiation and eventual beta-cell restoration.

PMID- 11522717
TI  - Muscle fiber composition and capillary density in Turner syndrome: evidence of
      increased muscle fiber size related to insulin resistance.
AB  - OBJECTIVE: To assess muscle fiber composition and capillary density in Turner
      syndrome, a condition linked with insulin resistance and increased frequency of
      type 2 diabetes, and link these findings with insulin sensitivity and physical
      fitness. RESEARCH DESIGN AND METHODS: A total of 10 patients with Turner syndrome
      who were off hormone replacement therapy (aged 32.7 +/- 8.9 years) and a control
      group of 14 normal women (aged 35.6 +/- 9.3 years) were studied. None of the
      participants had diabetes or any family history of type 2 diabetes. An oral
      glucose tolerance test was performed, and insulin sensitivity was assessed by
      homeostasis model assessment (HOMA) and a composite whole-body insulin
      sensitivity index (ISI(comp)). Physical fitness was assessed, and a muscle biopsy
      was obtained. RESULTS: Women with Turner syndrome were insulin resistant, as seen
      by a lower ISI(comp) (P = 0.003) and increased glucose (P < 0.0005) and insulin
      (P = 0.01) levels at 120 min. Impaired glucose tolerance was present in most
      Turner syndrome patients (6 of 10), but not in the control subjects. Women with
      Turner syndrome had an increased size of type IIa fibers (P = 0.01), whereas the
      size of their type I and IIa fibers were comparable with the control group. The
      groups did not differ in percentage of type I, Iia, or IIx fibers, and there was
      no difference in the capillary density. Significant correlations were found among
      ISI(comp), the HOMA index (R(HOMA)), and the mean area of type IIa fibers
      (ISI(comp): r = -0.632, P = 0.002; R(HOMA): r = 0.570, P = 0.006). Furthermore,
      capillaries/type IIa fibers correlated significantly with ISI(comp) (r = -0.618,
      P = 0.01). There were no significant correlations between VO(2max) and muscle
      fiber composition. CONCLUSIONS: Healthy women with Turner syndrome are
      characterized by impaired glucose tolerance, insulin resistance, low physical
      capacity, and enlarged type IIa muscle fibers, indicating diminished oxygen and
      substrate supply for metabolic processes. These findings could be indicative of a
      prediabetic state.

PMID- 11522718
TI  - Endothelial perturbation in children and adolescents with type 1 diabetes:
      association with markers of the inflammatory reaction.
AB  - OBJECTIVE: The progression of diabetic angiopathy is, in most cases,
      unpredictable. The aim of this study was to investigate early events that could
      influence the development of diabetic angiopathy. RESEARCH DESIGN AND METHODS:
      Circulating levels of von Willebrand factor (vWF) and tissue-plasminogen
      activator (tPA), defining endothelial perturbation, were measured in 40 young
      patients with type 1 diabetes. Patients were divided into two groups according to
      the duration of diabetes (group A, <1 year; group B, >1 year) and compared with a
      control group of age- and sex-matched healthy individuals. Prothrombin fragment 1
      and 2 (F(1+2)), tumor necrosis factor-alpha (TNF-alpha), and C-reactive protein
      (CRP) levels were also determined as markers of a prothrombotic state and
      inflammatory response. A total of 16 of the 20 children in group A were re
      examined after 12 months. RESULTS: Compared with either normal subjects or
      patients in group B, children in group A showed increased levels of vWF, tPA,
      F(1+2), TNF-alpha, and CRP. Significant direct correlations between TNF-alpha or
      CRP and either vWF, tPA, or F(1+2) were observed. Endothelial perturbation was
      shown in 70% of group A and 20% of group B. After 1 year, 16 of the 20 patients
      in group A showed a significant reduction in vWF, tPA, F(1+2), TNF-alpha, and CRP
      levels, whereas endothelial perturbation was reversed in 5 of these patients.
      CONCLUSIONS: Endothelial perturbation represents an early and, in some cases,
      reversible event in the chronology of type 1 diabetes in children. A correlation
      might exist between the initial inflammatory reaction and the appearance of
      endothelial perturbation.

PMID- 11522719
TI  - Diabetes and hypertension.

PMID- 11522720
TI  - Maternal transmission of type 2 diabetes varies by ethnic group: cross-sectional
      survey of Europeans and South Asians.

PMID- 11522721
TI  - Glucose instability is associated with a high level of circulating p-selectin.

PMID- 11522722
TI  - Epidemiology of nontraumatic lower-extremity amputation in area 7, Madrid,
      between 1989 and 1999: a population-based study.

PMID- 11522723
TI  - Increased risk of lower-extremity amputation among Caucasian diabetic patients on
      dialysis.

PMID- 11522724
TI  - Homogeneity of metabolic control in New South Wales and the Australian Capital
      Territory, Australia.

PMID- 11522725
TI  - Acute Charcot's arthropathy despite 11 years of normoglycemia after successful
      kidney and pancreas transplantation.

PMID- 11522726
TI  - Remnant-like particle cholesterol and insulin resistance in nonobese
      nonhypertensive Japanese glucose-tolerant relatives of type 2 diabetic patients.

PMID- 11522727
TI  - Glucodynamics and pharmacokinetics of 70/30 vs. 50/50 NPH/regular insulin
      mixtures after subcutaneous injection.

PMID- 11522728
TI  - Presence of autoantibodies to carbonic anhidrase II and lactoferrin in type 1
      diabetes: proposal of the concept of autoimmune exocrinopathy and endocrinopathy
      of the pancreas.

PMID- 11522729
TI  - Subcutaneous continuous glucose monitoring: feasibility of a new microdialysis
      based glucose sensor system.

PMID- 11522730
TI  - Serum concentrations of soluble vascular cell adhesion molecule-1 and E-selectin
      are elevated in insulin-resistant patients with type 2 diabetes.

PMID- 11522731
TI  - Response to Malone et al.

PMID- 11522733
TI  - Clinical research: at the crossroads.

PMID- 11522734
TI  - Intragastric volatile N-nitrosamines, nitrite, pH, and Helicobacter pylori during
      long-term treatment with omeprazole.
AB  - BACKGROUND & AIMS: This study evaluated the effect of long-term gastric acid
      suppressive therapy with omeprazole on intragastric levels of carcinogenic N
      nitrosamines and related parameters. METHODS: Forty-five patients on long-term
      omeprazole medication (mean, 35 months) and 13 healthy subjects without
      medication participated. Volatile N-nitrosamines were determined in gastric juice
      and urine. Intragastric pH, nitrite, nitrate, and H. pylori status were
      determined. DNA isolated from gastric biopsy specimens was analyzed for
      precarcinogenic alkyl-DNA adducts. RESULTS: The intragastric pH in patients was
      significantly higher compared with controls (P = 0.0001). Gastric nitrite levels
      in patients were nonsignificantly higher. There was no difference in total levels
      of intragastric volatile N-nitrosamines between patients and controls, however,
      urinary N-nitrosodimethylamine excretion was higher in patients (P = 0.001). On
      omeprazole, Helicobacter pylori-positive vs. -negative patients had a
      nonsignificantly higher intragastric nitrite level and higher urinary N
      nitrosodimethylamine excretion. No alkyl-DNA adducts could be detected in gastric
      epithelium. CONCLUSIONS: Increased intragastric pH caused by long-term treatment
      with omeprazole does not result in increased intragastric levels of nitrite and
      volatile N-nitrosamines. The significantly higher urinary N-nitrosamine excretion
      implies the risk of increased endogenous formation of N-nitrosamines during long
      term omeprazole treatment. This risk may be higher in H. pylori-positive
      patients.

PMID- 11522735
TI  - Symptoms associated with hypersensitivity to gastric distention in functional
      dyspepsia.
AB  - BACKGROUND & AIMS: Hypersensitivity to gastric distention has been reported in
      functional dyspepsia, but its characteristics and relevance to symptoms remain
      unclear. The aim of this study was to define hypersensitivity to gastric
      distention and its association to specific symptoms in functional dyspepsia.
      METHODS: We used a gastric barostat to study sensitivity to gastric distention in
      80 healthy subjects and in 160 functional dyspepsia patients. Demographic
      characteristics, gastric emptying, Helicobacter pylori status, gastric
      accommodation, and a dyspepsia symptom score were obtained from all patients and
      the relationship with visceral sensitivity was assessed using univariate and
      multivariate analysis. RESULTS: The increase of intra-balloon pressure over intra
      abdominal pressure needed to induce discomfort or pain is the most appropriate
      expression of sensitivity to gastric distention because it yields a meaningful
      lower range of normal and it is independent from age and body mass index.
      Hypersensitivity to gastric distention was found in 34% of the patients, who did
      not differ from the other patients in demographic and other pathophysiological
      characteristics. Hypersensitivity to distention was associated with a higher
      prevalence of postprandial pain, belching, and weight loss. CONCLUSIONS:
      Hypersensitivity to gastric distention is present in a subset of functional
      dyspepsia patients. It is associated with symptoms of postprandial epigastric
      pain, belching, and weight loss.

PMID- 11522736
TI  - Sacral nerve stimulation as a treatment for fecal incontinence.
AB  - BACKGROUND & AIMS: Sacral nerve stimulation is a proven therapeutic option for
      the treatment of some forms of urinary incontinence. Very recently, preliminary
      reports have given evidence for its efficacy in fecal incontinence (FI) too.
      METHODS: Since November 1998, 20 patients have been treated for severe FI. The
      cause of FI was mainly neurologic (n = 15), and was idiopathic in 5 patients.
      After temporary (subchronic) external stimulation over a period of 10-14 days,
      patients whose continence status improved underwent implantation of a permanent
      quadripolar lead and a subcutaneously implanted pulse generator. RESULTS: Acute
      (needle) testing revealed a positive pelvic floor response in 16 patients who
      underwent subsequent permanent implantation. The median number of incontinence
      episodes decreased from 6 episodes (3-15/21 days) to 2 (0-5/21 days). The time
      period of retention of a volume of saline causing an urge until definitive
      defecation was 2 minutes (range, 0-5 minutes) preoperatively and increased to 7.5
      minutes (2-15 minutes) postoperatively. Results of preoperative and postoperative
      (3 months) anal manometry showed a statistically significant increase in maximal
      resting and squeeze pressures. CONCLUSIONS: Sacral nerve stimulation seems to be
      a new and promising modality for patients with certain types of FI in whom
      conventional treatment options have failed to achieve an improvement.

PMID- 11522737
TI  - Intestinal cancer after cholecystectomy: is bile involved in carcinogenesis?
AB  - BACKGROUND & AIMS: Results concerning an association between cholecystectomy and
      right-sided colon cancer are inconsistent. Little is known about the relation
      between cholecystectomy and small bowel cancer. Therefore, we evaluated
      cholecystectomy and risk of bowel cancer. METHODS: Cholecystectomized patients,
      identified through the Swedish Inpatient Register, from 1965 through 1997, were
      followed up for subsequent cancer. The standardized incidence ratio (SIR)
      estimated relative risk. RESULTS: In total, 278,460 cholecystectomized patients,
      contributing 3,519,682 person-years, were followed up for a maximum of 33 years
      after surgery. Cholecystectomized patients had an increased risk of proximal
      intestinal adenocarcinoma, which gradually declined with increasing distance from
      the common bile duct. The risk was significantly increased for adenocarcinoma
      (SIR, 1.77; 95% confidence interval [CI], 1.37-2.24) and carcinoids of the small
      bowel (SIR, 1.71; 95% CI, 1.39-2.08), and right-sided colon cancer (SIR, 1.16;
      95% CI, 1.08-1.24). No association was found with more distal bowel cancer. The
      gradient was further pronounced when surgery of the common bile duct was
      included. The associations remained increased up to 33 years after
      cholecystectomy. No differences between sexes were found. CONCLUSIONS:
      Cholecystectomy increases the risk of intestinal cancer, a risk that declines
      with increasing distance from the common bile duct. Changes in the intestinal
      exposure to bile might be the underlying biological mechanism.

PMID- 11522738
TI  - Association between cholecystectomy and adenocarcinoma of the esophagus.
AB  - BACKGROUND & AIMS: Barrett's esophagus, which is linked to adenocarcinoma of the
      esophagus, is associated with reflux of bile. Duodenogastric reflux is increased
      after cholecystectomy. This study aims to evaluate if cholecystectomy is
      associated with an increased risk of adenocarcinoma of the esophagus. METHODS: A
      population-based cohort study of cholecystectomized patients in Sweden between
      1965 and 1997 cross-linked with the Swedish Cancer Register. RESULTS:
      Cholecystectomized patients had an increased risk of adenocarcinoma of the
      esophagus (standardized incidence ratio [SIR], 1.3; 95% confidence interval [CI],
      1.0-1.8). Esophageal squamous-cell carcinoma was not found to be associated with
      cholecystectomy (SIR, 0.9; 95% CI, 0.7-1.1). Patients with gallstone disease on
      whom surgery was not performed did not have an increased risk of adenocarcinoma
      or squamous-cell carcinoma of the esophagus. CONCLUSIONS: Cholecystectomy is
      associated with a moderately increased risk of adenocarcinoma of the esophagus,
      possibly by the toxic effect of refluxed duodenal juice on the esophageal mucosa.
      Further studies are needed regarding the link between bile reflux and esophageal
      carcinogenesis.

PMID- 11522739
TI  - Clinical studies in persistent diarrhea: dietary management with green banana or
      pectin in Bangladeshi children.
AB  - BACKGROUND & AIMS: Because of the beneficial intestinal effects of dietary
      fibers, we have evaluated the therapeutic effects of green banana or pectin in
      children with persistent diarrhea. METHODS: In a double-blind trial, 62 boys, age
      5-12 months, were randomly given a rice-based diet containing either 250 g/L of
      cooked green banana (n = 22) or 4 g/kg pectin (n = 19) or the rice-diet alone
      (control, n = 21), providing 54 kcal/dL daily for 7 days. Stool weight and
      consistency, frequency of vomiting and purging, and duration of illness were
      measured. RESULTS: Most children (60%) had no pathogens isolated from stools, 17%
      had rotavirus, 5% Vibrio cholerae, 4% Salmonella group B, and 11% had
      enterotoxigenic Escherichia coli infections. By day 3 posttreatment,
      significantly (P < 0.001) more children recovered from diarrhea receiving pectin
      or banana than controls (59%, 55%, and 15%, respectively). By day 4, these
      proportions correspondingly increased to 82%, 78%, and 23%, respectively, the
      study diet groups being significantly (P < 0.001) different than controls. Green
      banana and pectin significantly (P < 0.05) reduced amounts of stool, oral
      rehydration solution, intravenous fluid, and numbers of vomiting, and diarrheal
      duration. CONCLUSIONS: Green banana and pectin are useful in the dietary
      management of persistent diarrhea in hospitalized children and may also be useful
      to treat children at home.

PMID- 11522740
TI  - Role of acquired and hereditary thrombotic risk factors in colon ischemia of
      ambulatory patients.
AB  - BACKGROUND & AIMS: Hypercoagulable states may play an important role in the
      pathogenesis of colon ischemia. Aim of this study was to assess this hypothesis
      investigating the role of acquired and hereditary thrombotic risk factors in
      patients with definite diagnosis of colon ischemia. METHODS: We compared the
      frequency of antiphospholipid antibodies, protein C, protein S, and antithrombin
      deficiencies, factor V Leiden, prothrombin gene mutation G20210GA, and
      methylenetetrahydrofolate reductase C677T in 36 patients (23 men, 13 women; mean
      age, 64.8 years) with colon ischemia, 18 patients with diverticulitis, and 52
      healthy controls. RESULTS: The prevalence of antiphospholipid antibodies was
      significantly higher in patients with colon ischemia compared with inflammatory
      and healthy controls (19.4% vs. 0% and 1.9%). Among genetic factors, only factor
      V Leiden was significantly associated with colon ischemia (22.2% vs. 0% and
      3.8%). A combination of thrombophilic disorders was found in 25% of the cases.
      Overall, one or several prothrombotic abnormalities were present in 26 patients
      (72%). CONCLUSIONS: A comprehensive thrombophilic screening in colon ischemia
      reveals a congenital or acquired thrombophilic state in 72% of patients.
      Hereditary and acquired thrombotic risk factors may play an important role in the
      disease pathogenesis.

PMID- 11522742
TI  - Probiotic bacteria enhance murine and human intestinal epithelial barrier
      function.
AB  - BACKGROUND & AIMS: The probiotic compound, VSL#3, is efficacious as maintenance
      therapy in pouchitis and ulcerative colitis. The aim of this study was to
      determine the efficacy of VSL#3 as a primary therapy in the treatment of colitis
      in the interleukin (IL)-10 gene-deficient mouse. Mechanisms of action of VSL#3
      were investigated in T(84) monolayers. METHODS: IL-10 gene-deficient and control
      mice received 2.8 x 10(8) colony-forming units per day of VSL#3 for 4 weeks.
      Colons were removed and analyzed for cytokine production, epithelial barrier
      function, and inflammation. VSL#3 or conditioned media was applied directly to
      T(84) monolayers. RESULTS: Treatment of IL-10 gene-deficient mice with VSL#3
      resulted in normalization of colonic physiologic function and barrier integrity
      in conjunction with a reduction in mucosal secretion of tumor necrosis factor
      alpha and interferon gamma and an improvement in histologic disease. In vitro
      studies showed that epithelial barrier function and resistance to Salmonella
      invasion could be enhanced by exposure to a proteinaceous soluble factor secreted
      by the bacteria found in the VSL#3 compound. CONCLUSIONS: Oral administration of
      VSL#3 was effective as primary therapy in IL-10 gene-deficient mice, and had a
      direct effect on epithelial barrier function.

PMID- 11522741
TI  - Rho kinase regulates tight junction function and is necessary for tight junction
      assembly in polarized intestinal epithelia.
AB  - BACKGROUND & AIMS: Tight junctions are crucial determinants of barrier function
      in polarized intestinal epithelia and are regulated by Rho guanosine
      triphosphatase. Rho kinase (ROCK) is a downstream effector of Rho. METHODS: A
      specific inhibitor of ROCK, Y-27632, was used to examine the role of ROCK in the
      regulation of tight junctions in model intestinal (T84) cells by
      electrophysiologic, biochemical, morphologic, and molecular biologic approaches.
      RESULTS: ROCK inhibition induced reorganization of apical F-actin structures and
      enhanced paracellular permeability but did not alter the distribution or
      detergent solubility of tight junction proteins. Confocal microscopy showed
      colocalization of a subpool of ROCK with the tight junction protein zonula
      occludens 1. Inhibition of ROCK function by a dominant negative mutant of ROCK
      also produced reorganization of apical F-actin structures without disruption of
      tight junctions. ROCK inhibition in calcium switch assays showed that ROCK is
      necessary for the assembly of tight and adherens junctions. Upon calcium
      repletion, occludin, zonula occludens 1, and E-cadherin failed to redistribute to
      the intercellular junctions; assembly of the apical F-actin cytoskeleton was
      prevented; and barrier function failed to recover. CONCLUSIONS: We suggest that
      ROCK regulates intact tight junctions via its effects on the F-actin
      cytoskeleton. ROCK is also critical for assembly of the apical junctional
      proteins and the F-actin cytoskeleton organization during junctional formation.

PMID- 11522743
TI  - Genetic differences between adenocarcinomas arising in Barrett's esophagus and
      gastric mucosa.
AB  - BACKGROUND & AIMS: Barrett adenocarcinoma (BA+) and gastric adenocarcinoma
      comprise a related group of neoplasms that nevertheless have some distinct
      clinicopathologic characteristics. This study aimed at defining critical
      molecular abnormalities that may underlie differences between BA+ and gastric
      adenocarcinomas. METHODS: We used comparative genomic hybridization for the
      analyses of 34 xenografts of adenocarcinomas that arose from esophageal or
      gastric origin. RESULTS: All tumors, except one, exhibited DNA copy number
      alterations. Losses in 4q and 14q and gains at 2p and 17q were more frequent in
      proximal (esophageal, gastroesophageal junction [GEJ], and cardia) tumors than in
      distal (body and antrum) tumors (P <or= 0.050). These changes were significantly
      higher in BA+ compared with distal tumors (P <or= 0.040). In addition, losses in
      5q and gains at 20q were significantly higher in BA+ than in distal cancers (P
      <or= 0.040). Losses in 5q and 8p and gains at 2q, 6p, 12p, and 20q were
      significantly more frequent in BA+ tumors (P <or= 0.050) than in GEJ and cardiac
      tumors without associated Barrett's esophagus. Additionally, losses in 14q, which
      were common in proximal tumors, were more often seen in BA+ (P = 0.100) than in
      other proximal tumors. CONCLUSIONS: Although these adenocarcinomas share some
      common genetic alterations, the differences in the DNA copy numbers in BA+ cases
      suggest that unique genetic alterations may be involved in these cancers'
      development.

PMID- 11522744
TI  - Analysis of K-ras, APC, and beta-catenin in aberrant crypt foci in sporadic
      adenoma, cancer, and familial adenomatous polyposis.
AB  - BACKGROUND & AIMS: We have previously shown that aberrant crypt foci (ACF) are
      the putative precursor lesions of colorectal adenomas and subsequent cancer in
      humans using magnifying endoscopy. The present study was designed to investigate
      these genetic alterations in ACF biopsy specimens from normal subjects, familial
      adenomatous polyposis (FAP) or sporadic patients. METHODS: The non-FAP cases
      included 34 normal subjects, 35 colorectal adenoma patients, and 19 colorectal
      cancer patients; there were 4 FAP patients. Biopsies were performed on ACF by
      magnifying endoscopy. K-ras mutations were analyzed by 2-step polymerase chain
      reaction and restriction fragment length polymorphism, APC mutations by in vitro
      synthesized protein assay, and beta-catenin mutations by direct sequencing. Full
      length APC and beta-catenin were detected by immunofluorescence. RESULTS: In non
      FAP cases, K-ras mutations were detected in 82% (89/106) of nondysplastic ACF and
      63% (17/27) of dysplastic ACF. APC mutation and beta-catenin accumulation were
      not detected in non-FAP ACF, whereas in adenoma of these patients, positivity of
      APC mutation and beta-catenin accumulation were 78% (24/31), and that of K-ras
      mutation was 65% (20/31). FAP patients showed K-ras mutations in only 13% (1/8)
      of dysplastic ACF, which is the predominant form of ACF found in FAP. In FAP
      patients, somatic APC mutations were found in 100% of dysplastic ACF, as they are
      in adenoma. The frequency of K-ras mutations was 73% (8 of 11) in FAP adenoma.
      CONCLUSIONS: The data suggest that in sporadic colorectal carcinogenesis,
      assuming the biological implication of ACF as a precursor of adenomas, there is a
      route where K-ras mutation mainly occurs during the formation of ACF, which then
      become adenomas wherein APC mutation occurs. In FAP, however, somatic mutation of
      APC predominantly occurs during ACF formation, followed by K-ras mutation.

PMID- 11522745
TI  - Distinct chromosomal aberrations in Epstein-Barr virus-carrying gastric
      carcinomas tested by comparative genomic hybridization.
AB  - BACKGROUND & AIMS: Approximately 10% of gastric adenocarcinomas carry the human
      pathogenic Epstein-Barr virus (EBV). The role of EBV in the pathogenesis of these
      carcinomas remains to be established. METHODS: To obtain a comprehensive overview
      of chromosomal aberrations in EBV-carrying and EBV-negative gastric carcinomas we
      performed comparative genomic hybridization (CGH) on 44 gastric carcinomas, 10
      EBV-positive, and 34 EBV-negative. Additionally, DNA flow cytometry was done.
      RESULTS: Loss of chromosome 4p (P < 0.001) and of 11p (P < 0.02) was exclusively
      restricted to EBV-carrying gastric carcinomas. In addition, loss of 18q (P <
      0.02) was significantly more frequent in EBV-carrying gastric carcinomas. The
      latter involves loci, which have already been linked to gastric carcinogenesis
      such as the DCC and SMAD4 gene. In contrast, the losses on chromosome 4 and 11 do
      not yet harbor a gene related to gastric carcinogenesis. No significant
      correlation was found between DNA-ploidy and the EBV-status. A number of
      chromosomal aberrations were found at comparable frequencies in both groups,
      i.e., losses of chromosome 17, 12q, and loss of 1p. Interestingly, gains of 13q
      (10/34) and 3q (5/34) and loss of 1q (5/34) were solely observed in EBV-negative
      gastric carcinomas. CONCLUSIONS: These data indicate that EBV-carrying and EBV
      negative gastric carcinomas have different pathogenetic pathways in which EBV
      might play a crucial role.

PMID- 11522746
TI  - Macrophage migration inhibitory factor is an important mediator in the
      pathogenesis of gastric inflammation in rats.
AB  - BACKGROUND & AIMS: Macrophage migration inhibitory factor (MIF) has been shown to
      play a pivotal role in inflammatory and immune-mediated diseases. This study
      investigates the role of MIF in gastric inflammation. METHODS: Expression of MIF
      was examined in a rat gastric ulcer model induced by acetic acid, and the
      functional role of MIF in acute gastric ulcer was investigated by administration
      of a neutralizing anti-MIF antibody. RESULTS: MIF messenger RNA and protein were
      markedly up-regulated in acute gastric ulcer, which correlated with the
      accumulation of macrophages (P < 0.001) and neutrophils (P < 0.05) at the site of
      inflammation. Macrophages, like neutrophils, were the major inflammatory cells
      infiltrating the ulcer base and they strongly expressed inducible nitric oxide
      synthase. However, macrophages, not neutrophils, were a rich source of MIF
      production in acute gastric ulcer. In vivo and in vitro blockade of MIF with the
      neutralizing anti-MIF antibody significantly inhibited the marked up-regulation
      of MIF, tumor necrosis factor alpha, inducible nitric oxide synthase, and
      intercellular adhesion molecule-1. This was associated with the marked inhibition
      of macrophage (70% reduced) and neutrophil (60% reduced) accumulation and
      activation, thus reducing ulcer sizes and attenuating ulceration. CONCLUSIONS:
      This study has shown that MIF was markedly up-regulated during acute gastric
      ulcer. Inhibition of acute gastric ulcer by blockade of MIF indicates that MIF is
      a key inflammatory mediator and plays a pathogenic role in gastric inflammation.

PMID- 11522747
TI  - Short-chain fatty acids induce intestinal epithelial heat shock protein 25
      expression in rats and IEC 18 cells.
AB  - BACKGROUND & AIMS: Because short-chain fatty acids (SCFAs) and heat shock
      proteins (hsps) confer protection to intestinal epithelia cells (IECs), we
      studied whether SCFAs modulate IEC hsp expression. METHODS: Hsp 25, hsp72, and
      hsc73 protein expression in rat intestinal tissues and IEC-18 cells were
      determined by Western blot and immunohistochemistry. Cell survival under
      conditions of oxidant stress (monochloramine) was determined using (51)Cr release
      in hsp25 cDNA anti-sense and sense-transfected cells expressing minimal and
      increased hsp25, respectively. RESULTS: Butyrate induces a time- and
      concentration-dependent increase in hsp25, but not hsp72 or hsc73, protein
      expression in rat IEC-18 cells but not 3T3 fibroblasts. Other SCFAs, including
      the poorly metabolized isobutyate, also induced selective expression of hsp25.
      Butyrate treatment significantly improved the ability of IEC-18 cells to
      withstand oxidant (monochloramine) injury. This effect could be blocked in cells
      in which hsp25 induction by butyrate was blocked by stable hsp25 antisense
      transfection. Additionally, hsp25-transfected overexpressing IEC-18 cells showed
      increased resistance to monochloramine. In vivo, increasing dietary fiber
      increased colonic, but not proximal, ileal hsp25 while having no effect on hsp72
      or hsc73 expression. CONCLUSIONS: SCFAs, the predominant anions of colonic fluid
      derived from bacterial flora metabolism of luminal carbohydrates, protect IECs
      against oxidant injury, an effect mediated in part by cell-specific hsp25
      induction.

PMID- 11522748
TI  - Islet amyloid polypeptide is not a satisfactory marker for detecting pancreatic
      cancer.
AB  - BACKGROUND & AIMS: Islet amyloid polypeptide (IAPP) levels are elevated in
      pancreatic cancer and may be a useful marker of pancreatic cancer-associated
      diabetes. The aim of this study was to compare the sensitivity and specificity
      for pancreatic cancer of IAPP with that of CA19-9, examine clinical
      characteristics of diabetes in pancreatic cancer, and define the relationship of
      IAPP to diabetes of pancreatic cancer. METHODS: Fasting serum glucose, IAPP, and
      CA 19-9 were measured in 130 subjects with pancreatic cancer, 250 subjects with
      other pancreatic and peripancreatic diseases, and 116 controls. In pancreatic
      cancer patients, we noted tumor stage and the presence and duration of diabetes.
      RESULTS: IAPP was markedly elevated in pancreatic cancer, especially in patients
      with diabetes. However, the sensitivity of IAPP for pancreatic cancer was less
      than that of CA 19-9 (40% vs. 75%; P < 0.001). Diabetes was present in 46% of
      pancreatic cancers and 55% of resectable tumors. In pancreatic cancer with
      diabetes, the sensitivity of IAPP was only 50%. In resectable cancer it was 27%.
      CONCLUSIONS: IAPP is elevated in pancreatic cancer but is not sensitive enough to
      replace or complement existing tests. Diabetes occurs early and frequently in
      pancreatic cancer. Development of a sensitive and specific marker for pancreatic
      associated diabetes might lead to diagnosis of resectable pancreatic cancer.

PMID- 11522749
TI  - Acute hepatitis C without and with schistosomiasis: correlation with hepatitis C
      specific CD4(+) T-cell and cytokine response.
AB  - BACKGROUND & AIMS: Immune responses during the first few months of acute
      hepatitis C virus (HCV) infection seem crucial for viral control, but the
      relationship of these responses to natural history is poorly characterized.
      METHODS: This prospective study investigated the HCV-specific CD4(+) and cytokine
      responses in patients with acute HCV hepatitis with or without Schistosoma
      mansoni coinfection, a parasitic infection with T helper (Th) 2 immune bias. HCV
      specific CD4(+) proliferative responses and cytokine production in peripheral
      blood mononuclear cells were correlated with liver biopsy results at 6 months and
      at the end of follow-up. RESULTS: Whereas 5 of 15 patients with HCV alone
      recovered from acute HCV, all (17 of 17) patients with S. mansoni coinfection
      progressed to histologically proven chronic hepatitis. Coinfected patients had
      either absent or transient weak HCV-specific CD4(+) responses with Th0/Th2
      cytokine production. The magnitude of the HCV-specific CD4(+) response at week 12
      was inversely correlated with the fibrosis progression rate in chronically
      infected patients. CONCLUSIONS: Patients with acute hepatitis C and
      schistosomiasis coinfection cannot clear viremia and show rapid progression once
      chronic infection is established. This rapid progression is associated with a
      strong Th2 response in peripheral immune responses, suggesting that early
      development of vigorous Th1 responses not only facilitates clearance but delays
      disease progression.

PMID- 11522751
TI  - Hepatic autoantigens in patients with autoimmune polyendocrinopathy-candidiasis
      ectodermal dystrophy.
AB  - BACKGROUND & AIMS: Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy
      (APECED) is caused by mutations of both copies of the autoimmune regulator (AIRE)
      gene. It is characterized by susceptibility to mucocutaneous candidiasis and
      multiple autoimmune lesions. A serious disease component is hepatitis. To
      identify diagnostic autoantibodies for APECED hepatitis, sera from 64 patients
      with APECED were screened for autoantibodies established in the diagnosis of
      idiopathic autoimmune hepatitis, and for autoantibodies against 10 cytochrome
      P450s. METHODS: Screening methods were indirect immunofluorescence, Western blot,
      Ouchterlony gel diffusion, enzyme-linked immunosorbent assay, and
      immunoprecipitation. RESULTS: Anti-liver microsomal antibodies were detected in
      50% of the patients with APECED hepatitis and 11% of those without hepatitis.
      Prevalences of antinuclear, smooth muscle, anti-liver cytosol, anti-soluble liver
      protein/liver pancreas, and anti-CYP2D6 autoantibodies were 9%, 6%, 3%, 0%, and
      0%, respectively. CYP1A1, CYP2B6, CYP1A2, and CYP2A6 were identified as
      autoantigens. Thirty percent of patients with anti-CYP2A6 and 100% of patients
      with anti-CYP1A2 were affected by hepatitis. Despite the high specificity of anti
      CYP1A2 for APECED hepatitis, its sensitivity was low (50%). Anti-CYP2A6 and anti
      CYP1A2 were not detected in patients with autoimmune hepatitis (N = 68) or
      nonhepatitic controls (N = 81). CONCLUSIONS: Anti-CYP1A2 is a highly specific but
      insensitive marker for APECED hepatitis. No clinical correlation was observed for
      anti-CYP2A6. Autoimmune hepatitis and APECED hepatitis are characterized by
      different molecular targets of autoantibodies with no overlap.

PMID- 11522750
TI  - Biglycan is overexpressed in pancreatic cancer and induces G1-arrest in
      pancreatic cancer cell lines.
AB  - BACKGROUND & AIMS: Biglycan (PG-I), a component of the extracellular matrix
      (ECM), is overexpressed in pancreatic cancer. To determine possible matrix-tumor
      interactions, we investigated the effects of PG-I on pancreatic cancer. METHODS:
      PG-I expression in cell lines and tissue samples was examined by Northern blot
      and immunofluorescence. The effect of PG-I on proliferation was determined by
      measuring activity of Ras, ERK, Rb, [(3)H]-thymidine incorporation, and cell
      cycle analysis. Expression of cyclin A, B1, D1, E1, G1, PCNA, p21, and p27 was
      analyzed by Northern and Western blots. RESULTS: PG-I was overexpressed in the
      ECM of pancreatic cancer samples compared with normal pancreas or chronic
      pancreatitis tissues. Addition of transforming growth factor (TGF)-beta induced
      PG-I expression in HFL and HFFF2 fibroblasts as well as in the pancreatic cancer
      cell line PANC-1. PG-I inhibited growth of both TGF-beta-responsive and TGF-beta
      unresponsive pancreatic cancer cells by inducing G1-arrest, which is accompanied
      by an increase of p27 and reduction of cyclin A and proliferating cell nuclear
      antigen. Furthermore, endogenous Ras and ERK activation was partly reduced by PG
      I in vitro. CONCLUSIONS: The ECM protein PG-I inhibits growth by arresting
      pancreatic cancer cells in G1 and may be part of a host defense mechanism aimed
      at slowing down pancreatic tumor progression.

PMID- 11522752
TI  - Claudin-4: a new target for pancreatic cancer treatment using Clostridium
      perfringens enterotoxin.
AB  - BACKGROUND & AIMS: Recently, several members of the claudin family have been
      identified as integral constituents of tight junctions. Using expression
      profiling, we previously found claudin-4 to be overexpressed in pancreatic
      cancer. Because claudin-4 has been described as a receptor for the cytotoxic
      Clostridium perfringens enterotoxin (CPE), we investigated the effect of CPE on
      pancreatic cancer cells. METHODS: Expression of claudin-4 was analyzed by
      Northern blots. In vitro toxicity of CPE was determined by trypan blue exclusion
      and the (86)Rb-release assay. The in vivo effect of CPE was studied in claudin-4
      expressing nude mouse xenografts of the Panc-1 cell line. RESULTS: Expression
      analyses showed that claudin-4 was overexpressed in most pancreatic cancer
      tissues and cell lines and several other gastrointestinal tumors. CPE led to an
      acute dose-dependent cytotoxic effect, restricted to claudin-4-expressing cells
      and dependent on claudin-4 expression levels. Furthermore, transforming growth
      factor beta was identified as a negative modulator of both claudin-4 expression
      and susceptibility to CPE. In vivo, intratumoral injections of CPE in Panc-1
      xenografts led to large areas of tumor cell necrosis and significant reduction of
      tumor growth. CONCLUSIONS: Our findings suggest that targeting claudin-4
      expressing tumors with CPE represents a promising new treatment modality for
      pancreatic cancer and other solid tumors.

PMID- 11522754
TI  - Chromosomal allelic imbalance evolving from liver cirrhosis to hepatocellular
      carcinoma.
AB  - BACKGROUND & AIMS: Cirrhotic nodules have long been assumed to be the
      precancerous lesions of hepatocellular carcinoma (HCC). We thus investigated the
      allelic imbalance (AI) in cirrhotic nodules to define the genetic aberrations in
      early hepatocarcinogenesis. METHODS: One hundred eighty cirrhotic nodules from 7
      female patients with HCC were collected by microdissection. Their clonality
      nature was assessed by examining the X chromosome methylation pattern. AI in
      monoclonal cirrhotic nodules and the corresponding HCCs were analyzed with
      microsatellite polymorphic markers. RESULTS: One hundred one out of 180 nodules
      (56.1%) were monoclonal and the average fractional AI (FAI) was 21%, lower than
      the 40% in HCC. Their overall AI patterns differed significantly from that in HCC
      (P < 0.001) with FAI on 2q, 4q, 8p, and Xq higher than the mean value. Comparison
      of FAI in nodules (stratified by increasing total AI events) further revealed a
      progressive increase of FAI on 4q, 8p, and Xq. In contrast, FAI on 1p, 13q, 16q,
      and 17p were low in nodules but rose above the mean only in HCC. CONCLUSIONS:
      About half of the cirrhotic nodules are monoclonal and already have chromosome
      aberrations. AI on 4q, 8p, and Xq may be the earlier mutations, whereas AI on 1p,
      13q, 16q, and 17p occurs late in hepatocarcinogenesis.

PMID- 11522753
TI  - Gliotoxin stimulates the apoptosis of human and rat hepatic stellate cells and
      enhances the resolution of liver fibrosis in rats.
AB  - BACKGROUND & AIMS: Hepatic stellate cells (HSCs) play a pivotal role in liver
      fibrosis and stimulating their apoptosis could be an effective treatment for
      liver fibrosis. METHODS: Activated HSCs, hepatocytes, and rats with liver
      fibrosis were treated with gliotoxin. RESULTS: Addition of gliotoxin to activated
      (alpha-smooth muscle actin positive) rat and human HSCs resulted in morphologic
      alterations typical of apoptosis. Within 2-3 hours of incubation, caspase 3
      activity was markedly induced and caspase inhibitor 1 (Z-VAD-FMK)-sensitive
      oligonucleosome-length DNA fragments were detectable by gel electrophoresis of
      low molecular weight DNA. Apoptosis was widespread as judged by fluorescence
      activated cell sorter analysis and terminal deoxynucleotidyl transferase-mediated
      deoxyuridine triphosphate nick-end labeling staining in both rat and human HSCs
      at concentrations that had no effect on the viability of rat hepatocytes.
      Gliotoxin treatment significantly reduced the number of activated stellate cells
      and mean thickness of bridging fibrotic septae in livers from rats treated with
      carbon tetrachloride. CONCLUSIONS: These data demonstrate proof-of-concept that
      by up-regulating HSC apoptosis, the extent of fibrosis can be decreased in
      inflammatory liver injury.

PMID- 11522755
TI  - Nonalcoholic steatohepatitis.
AB  - Nonalcoholic steatohepatitis (NASH) is a condition characterized by hepatomegaly,
      elevated serum aminotransferase levels, and a histologic picture similar to
      alcoholic hepatitis in the absence of alcohol abuse. Most patients with NASH are
      obese women, and many have diabetes mellitus, hypercholesterolemia, or
      hypertriglyceridemia. NASH has also been associated with a number of metabolic
      conditions, surgical procedures, and drug treatments. Most patients are
      asymptomatic. The most common sign of NASH is hepatomegaly. Stigmata of chronic
      liver disease are rare. Laboratory abnormalities include a 2-4-fold elevation of
      serum aminotransferase levels; other liver function test results are usually
      normal. Histologically, there is moderate to severe macrovesicular steatosis and
      lobular hepatitis with necrosis or ballooning degeneration and/or fibrosis. The
      pathogenesis of NASH is poorly understood, but lipid peroxidation and oxidative
      stress are the leading culprits. The natural history of NASH is unknown, but NASH
      seems to be a stable disease in most patients. Treatment of NASH is unproven, but
      weight reduction is recommended in obese patients. Small pilot studies of several
      drugs have shown promise, but large randomized clinical trials are awaited.
      Orthotopic liver transplantation is the treatment of choice for end-stage liver
      disease secondary to NASH.

PMID- 11522756
TI  - Thrombophilia and colon ischemia: Aura popularis?

PMID- 11522757
TI  - Tumor genomics vs. tumor genetics: a paradigm shift?

PMID- 11522758
TI  - Is the appendix a vestigial organ? Its role in ulcerative colitis.

PMID- 11522759
TI  - What will you be when you grow up?

PMID- 11522760
TI  - A potential new hepatitis agent: making SEN-se of the data.

PMID- 11522761
TI  - Helicobacter pylori and nonulcer dyspepsia: looking beyond the bug.

PMID- 11522764
TI  - BrainImageJ: a Java-based framework for interoperability in neuroscience, with
      specific application to neuroimaging.
AB  - The Human Brain Project consortium continues to struggle with effective sharing
      of tools. To facilitate reuse of its tools, the Stanford Psychiatry Neuroimaging
      Laboratory (SPNL) has developed BrainImageJ, a new software framework in Java.
      The framework consists of two components-a set of four programming interfaces and
      an application front end. The four interfaces define extension pathways for new
      data models, file loaders and savers, algorithms, and visualization tools. Any
      Java class that implements one of these interfaces qualifies as a BrainImageJ
      plug-in-a self-contained tool. After automatically detecting and incorporating
      new plug-ins, the application front end transparently generates graphical user
      interfaces that provide access to plug-in functionality. New plug-ins
      interoperate with existing ones immediately through the front end. BrainImageJ is
      used at the Stanford Psychiatry Neuroimaging Laboratory to develop image-analysis
      algorithms and three-dimensional visualization tools. It is the goal of our
      development group that, once the framework is placed in the public domain, it
      will serve as an interlaboratory platform for designing, distributing, and using
      interoperable tools.

PMID- 11522763
TI  - A four-dimensional probabilistic atlas of the human brain.
AB  - The authors describe the development of a four-dimensional atlas and reference
      system that includes both macroscopic and microscopic information on structure
      and function of the human brain in persons between the ages of 18 and 90 years.
      Given the presumed large but previously unquantified degree of structural and
      functional variance among normal persons in the human population, the basis for
      this atlas and reference system is probabilistic. Through the efforts of the
      International Consortium for Brain Mapping (ICBM), 7,000 subjects will be
      included in the initial phase of database and atlas development. For each
      subject, detailed demographic, clinical, behavioral, and imaging information is
      being collected. In addition, 5,800 subjects will contribute DNA for the purpose
      of determining genotype- phenotype-behavioral correlations. The process of
      developing the strategies, algorithms, data collection methods, validation
      approaches, database structures, and distribution of results is described in this
      report. Examples of applications of the approach are described for the normal
      brain in both adults and children as well as in patients with schizophrenia. This
      project should provide new insights into the relationship between microscopic and
      macroscopic structure and function in the human brain and should have important
      implications in basic neuroscience, clinical diagnostics, and cerebral disorders.

PMID- 11522765
TI  - An integrated software suite for surface-based analyses of cerebral cortex.
AB  - The authors describe and illustrate an integrated trio of software programs for
      carrying out surface-based analyses of cerebral cortex. The first component of
      this trio, SureFit (Surface Reconstruction by Filtering and Intensity
      Transformations), is used primarily for cortical segmentation, volume
      visualization, surface generation, and the mapping of functional neuroimaging
      data onto surfaces. The second component, Caret (Computerized Anatomical
      Reconstruction and Editing Tool Kit), provides a wide range of surface
      visualization and analysis options as well as capabilities for surface
      flattening, surface-based deformation, and other surface manipulations. The third
      component, SuMS (Surface Management System), is a database and associated user
      interface for surface-related data. It provides for efficient insertion,
      searching, and extraction of surface and volume data from the database.

PMID- 11522766
TI  - A DBMS-based medical teleconferencing system.
AB  - This article presents the design of a medical teleconferencing system that is
      integrated with a multimedia patient database and incorporates easy-to-use tools
      and functions to effectively support collaborative work between physicians in
      remote locations. The design provides a virtual workspace that allows physicians
      to collectively view various kinds of patient data. By integrating the
      teleconferencing function into this workspace, physicians are able to conduct
      conferences using the same interface and have real-time access to the database
      during conference sessions. The authors have implemented a prototype based on
      this design. The prototype uses a high-speed network test bed and a manually
      created substitute for the integrated patient database.

PMID- 11522767
TI  - Considerations for the design of a Web-based clinical monitoring and educational
      system for elderly patients.
AB  - Designing a Web system for elderly patients requires attention to the users'
      functional impairments and inexperience with computers. The authors reviewed
      published guides for the design of Web-based clinical systems for elderly
      patients and identified additional design considerations that have not been
      reported in the literature. The resulting recommendations are related to the
      system interface, the training and support of users, and the content of Web
      pages. The recommendations can be used as design objectives for Web-based systems
      for elderly patients, which emphasize system usability and aim to optimize
      patients' error-free use of these systems.

PMID- 11522768
TI  - Evaluation of a computerized diagnostic decision support system for patients with
      pneumonia: study design considerations.
AB  - Planning the clinical evaluation of a computerized decision support system
      requires a strategy that encompasses the different aspects of the clinical
      problem, the technical difficulties of software and hardware integration and
      implementation, the behavioral aspects of the targeted users, and the discipline
      of study design. Although clinical information systems are becoming more widely
      available, only a few decision support systems have been formally evaluated in
      clinical environments. Published accounts of difficulties associated with the
      clinical evaluation of decision support systems remain scarce. The authors report
      on a variety of behavioral, logistical, technical, clinical, cost, and work flow
      issues that they had to address when choosing a study design for a clinical trial
      for the evaluation of an integrated, real-time decision support system for the
      automatic identification of patients likely to have pneumonia in an emergency
      department. In the absence of a true gold standard, they show how they created a
      credible, clinically acceptable, and economical reference standard for the
      diagnosis of pneumonia, to determine the overall accuracy of the system. For the
      creation of a reference standard, they describe the importance of recognizing
      verification bias and avoiding it. Finally, advantages and disadvantages of
      different study designs are explored with respect to the targeted users and the
      clinical setting.

PMID- 11522769
TI  - Evaluation of a command-line parser-based order entry pathway for the Department
      of Veterans Affairs electronic patient record.
AB  - OBJECTIVE: To improve and simplify electronic order entry in an existing
      electronic patient record, the authors developed an alternative system for
      entering orders, which is based on a command- interface using robust and simple
      natural-language techniques. DESIGN: The authors conducted a randomized
      evaluation of the new entry pathway, measuring time to complete a standard set of
      orders, and users' satisfaction measured by questionnaire. A group of 16
      physician volunteers from the staff of the Department of Veterans Affairs Puget
      Sound Health Care System-Seattle Division participated in the evaluation.
      RESULTS: Thirteen of the 16 physicians (81%) were able to enter medical orders
      more quickly using the natural-language-based entry system than the standard
      graphical user interface that uses menus and dialogs (mean time spared, 16.06 +/-
      4.52 minutes; P=0.029). Compared with the graphical user interface, the command-
      based pathway was perceived as easier to learn (P<0.01), was considered easier to
      use and faster (P<0.01), and was rated better overall (P<0.05). CONCLUSION:
      Physicians found the command- interface easier to learn and faster to use than
      the usual menu-driven system. The major advantage of the system is that it
      combines an intuitive graphical user interface with the power and speed of a
      natural-language analyzer.

PMID- 11522770
TI  - Physician satisfaction with two order entry systems.
AB  - OBJECTIVES: In the wake of the Institute of Medicine report, To Err Is Human:
      Building a Safer Health System (LT Kohn, JM Corrigan, MS Donaldson, eds;
      Washington, DC: National Academy Press, 1999), numerous advisory panels are
      advocating widespread implementation of physician order entry as a means to
      reduce errors and improve patient safety. Successful implementation of an order
      entry system requires that attention be given to the user interface. The authors
      assessed physician satisfaction with the user interface of two different order
      entry systems-a commercially available product, and the Department of Veterans
      Affairs Computerized Patient Record System (CPRS). DESIGN AND MEASUREMENT: A
      standardized instrument for measuring user satisfaction with physician order
      entry systems was mailed to internal medicine and medicine-pediatrics house staff
      physicians. The subjects answered questions on each system using a 0 to 9 scale.
      RESULTS: The survey response rates were 63 and 64 percent for the two order entry
      systems. Overall, house staff were dissatisfied with the commercial system,
      giving it an overall mean score of 3.67 (95 percent confidence interval [95%CI],
      3.37-3.97). In contrast, the CPRS had a mean score of 7.21 (95% CI, 7.00-7.43),
      indicating that house staff were satisfied with the system. Overall satisfaction
      was most strongly correlated with the ability to perform tasks in a
      "straightforward" manner. CONCLUSIONS: User satisfaction differed significantly
      between the two order entry systems, suggesting that all order entry systems are
      not equally usable. Given the national usage of the two order entry systems
      studied, further studies are needed to assess physician satisfaction with use of
      these same systems at other institutions.

PMID- 11522771
TI  - Human Brain Program Research Progress in biomedical imaging/neuroscience, 2001.

PMID- 11522772
TI  - UMLS concept indexing for production databases: a feasibility study.

PMID- 11522773
TI  - Medical informatics and health care in Oman.

PMID- 11522774
TI  - Prion protein protects human neurons against Bax-mediated apoptosis.
AB  - The function of the cellular prion protein (PrP) is still poorly understood. We
      present here an unprecedented role for PrP against Bax-mediated neuronal
      apoptosis and show that PrP potently inhibits Bax-induced cell death in human
      primary neurons. Deletion of four octapeptide repeats of PrP (PrPDeltaOR) and
      familial D178N and T183A PrP mutations completely or partially eliminate the
      neuroprotective effect of PrP. PrP remains anti-apoptotic despite truncation of
      the glycosylphosphatidylinositol (GPI) anchor signal peptide, indicating that the
      neuroprotective form of PrP does not require the abundant cell surface GPI
      anchored PrP. Our results implicate PrP as a potent and novel anti-apoptotic
      protein against Bax-mediated cell death.

PMID- 11522775
TI  - GRIM-19, a cell death regulatory gene product, is a subunit of bovine
      mitochondrial NADH:ubiquinone oxidoreductase (complex I).
AB  - The sequences of 42 subunits of NADH:ubiquinone oxidoreductase (complex I) from
      bovine heart mitochondria have been described previously. Seven are encoded by
      mitochondrial DNA, whereas the remaining 35 are nuclear gene products imported
      into the organelle from the cytoplasm. An additional protein, which does not
      correspond to any previously known subunit of the complex I assembly, has now
      been detected. Denaturing gels of subcomplex Ilambda, the hydrophilic arm of
      complex I, clearly show a hitherto unidentified band, which was digested with
      trypsin and subjected to mass-spectrometric analysis to provide several peptide
      sequences, used in cDNA cloning and sequencing. Measurement of the intact protein
      mass indicated that the N terminus is acetylated. The new complex I subunit
      (B16.6) is the bovine homolog of GRIM-19, the product of a cell death regulatory
      gene induced by interferon-beta and retinoic acid, thus providing a new link
      between the mitochondrion and its electron-transport chain and apoptotic cell
      death.

PMID- 11522776
TI  - CCAAT/enhancer-binding proteins alpha and beta negatively influence the capacity
      of tumor necrosis factor alpha to up-regulate the human cytomegalovirus IE1/2
      enhancer/promoter by nuclear factor kappaB during monocyte differentiation.
AB  - Recently we demonstrated that the ability of tumor necrosis factor alpha
      (TNFalpha) to stimulate the human cytomegalovirus (HCMV) IE1/2 enhancer/promoter
      activity in myeloid progenitor-like cells decreases when these cells
      differentiate into promonocytic cells. In addition, TNFalpha stimulation in the
      progenitor-like cell line HL-60 was shown to be mediated by nuclear factor kappaB
      (NF-kappaB) activation and its binding to the 18-base pair sequence motifs of the
      IE1/2 enhancer. We demonstrate here that the cell differentiation-dependent
      reduction of TNFalpha stimulation is not due to insufficient NF-kappaB activation
      but correlates with increased synthesis of the monocyte differentiation
      associated factors CCAAT/enhancer-binding protein (C/EBP) alpha and beta.
      Overexpression of C/EBPalpha/beta in HL-60 cells, which normally produce only
      very small amounts of C/EBP, stimulated the basal activity of the promoter in the
      absence of NF-kappaB but suppressed the stimulatory effect of TNFalpha. A novel
      C/EBP-binding site was identified in the IE1/2 enhancer directly downstream of a
      NF-kappaB site. In order to understand the mechanisms of interaction, we used an
      IE1/2 promoter mutant that failed to bind C/EBP at this position and several
      constructs that contained exclusively NF-kappaB- and/or C/EBP-binding sites
      upstream of the minimal IE1/2 promoter. We could demonstrate that C/EBPalpha/beta
      interacts with NF-kappaB p65 and displays inhibitory activity even in the absence
      of direct DNA binding by forming p65-C/EBP-containing protein complexes bound to
      the NF-kappaB site. Moreover, C/EBP binding to the DNA adjacent to NF-kappaB
      supports the down-regulatory effect of C/EBPs possibly due to stabilization of a
      multimeric NF-kappaB-C/EBP complex. Our results show that cell differentiation
      factors may interfere with TNFalpha-induced human cytomegalovirus gene
      (re)activation.

PMID- 11522777
TI  - Gene correction of integrin beta4-dependent pyloric atresia-junctional
      epidermolysis bullosa keratinocytes establishes a role for beta4 tyrosines 1422
      and 1440 in hemidesmosome assembly.
AB  - The cytoplasmic domain of beta4 integrin contains two pairs of fibronectin-like
      repeats separated by a connecting segment. The connecting segment harbors a
      putative tyrosine activation motif in which tyrosines 1422 and 1440 are
      phosphorylated in response to alpha6beta4 binding to laminin-5. Primary beta4
      null keratinocytes, obtained from a newborn suffering from lethal junctional
      epidermolysis bullosa, were stably transduced with retroviruses carrying a full
      length beta4 cDNA or a beta4 cDNA with phenylalanine substitutions at Tyr-1422
      and Tyr-1440. Hemidesmosome assembly was evaluated on organotypic skin cultures.
      beta4-corrected keratinocytes were indistinguishable from normal cells in terms
      of alpha6beta4 expression, the localization of hemidesmosome components, and
      hemidesmosome structure and density, suggesting full genetic and functional
      correction of beta4-null keratinocytes. In cultures generated from
      beta4(Y1422F/Y1440F) keratinocytes, beta4 mutants as well as alpha6 integrin,
      HD1/plectin, and BP180 were not concentrated at the dermal-epidermal junction.
      Furthermore, the number of hemidesmosomes was strikingly reduced as compared with
      beta4-corrected keratinocytes. The rare hemidesmosomes detected in
      beta4(Y1422F/Y1440F) cells were devoid of sub-basal dense plates and of inner
      cytoplasmic plaques with keratin filament insertion. Collectively, our data
      demonstrate that the beta4 tyrosine activation motif is not required for the
      localization of alpha6beta4 at the keratinocyte plasma membrane but is essential
      for optimal assembly of bona fide hemidesmosomes.

PMID- 11522778
TI  - Roles of the exposed aromatic residues in crystalline chitin hydrolysis by
      chitinase A from Serratia marcescens 2170.
AB  - Four exposed aromatic residues, two in the N-terminal domain (Trp-69 and Trp-33)
      and two in the catalytic domain (Trp-245 and Phe-232) of Serratia marcescens
      chitinase A, are linearly aligned with the deep catalytic cleft. To investigate
      the importance of these residues in the binding activity and hydrolyzing activity
      against insoluble chitin, site-directed mutagenesis to alanine was carried out.
      The substitution of Trp-69, Trp-33, or Trp-245 significantly reduced the binding
      activity to both highly crystalline beta-chitin and colloidal chitin. The
      substitution of Phe-232, which is located closest to the catalytic cleft, did not
      affect the binding activity. On the other hand, the hydrolyzing activity against
      beta-chitin microfibrils was significantly reduced by the substitution of any one
      of the four aromatic residues including Phe-232. None of the mutations reduced
      the hydrolyzing activity against soluble substrates. These results clearly
      demonstrate that the four exposed aromatic residues are essential determinants
      for crystalline chitin hydrolysis. Three of them, two in the N-terminal domain
      and one in the catalytic domain, play vital roles in the chitin binding. Phe-232
      appeared to be important for guiding the chitin chain into the catalytic cleft.
      Based on these observations, a model for processive hydrolysis of crystalline
      chitin by chitinase A is proposed.

PMID- 11522779
TI  - Regulation of cAMP-responsive element-binding protein-mediated transcription by
      the SNF2/SWI-related protein, SRCAP.
AB  - SRCAP (SNF2-related CPB activator protein) belongs to the SNF2 family of proteins
      whose members participate in various aspects of transcriptional regulation,
      including chromatin remodeling. It was identified by its ability to bind to cAMP
      responsive-binding protein (CREB)-binding protein (CBP), and it increases the
      transactivation function of CBP. The phosphoenolpyruvate carboxykinase (PEPCK)
      promoter was used as a model system to explore the role of SRCAP in the
      regulation of transcription mediated by factors that utilize CBP as a
      coactivator. We show that transcription of a PEPCK chloramphenicol
      acetyltransferase (CAT) reporter gene activated by protein kinase A (PKA) is
      enhanced 7-fold by SRCAP. In the absence of PKA this SRCAP-mediated enhancement
      does not occur, suggesting that SRCAP functions as a coactivator for PKA
      activated factors such as CREB. Replacing the PEPCK promoter binding site for
      CREB with a binding site for Gal4 (DeltaCRE (cAMP-responsive element) Gal4 PEPCK
      CAT reporter gene) blocks the ability of SRCAP to activate transcription despite
      the presence of PKA. Expression of a Gal-CREB chimera restores the ability of PKA
      to regulate transcription of the DeltaCRE Gal4 PEPCK gene and restored the
      ability of SRCAP to stimulate PKA-activated transcription. In addition, SRCAP in
      the presence of PKA enhances the ability of the Gal-CREB chimera to activate
      transcription of a Gal-CAT reporter gene that contains only binding sites for
      Gal4. SRCAP binds to CBP amino acids 280-460, a region that is important for CBP
      to function as a coactivator for CREB. Overexpression of a SRCAP peptide
      corresponding to this CBP binding domain acts as a dominant negative inhibitor of
      CREB-mediated transcription. Structure-function studies were done to explore the
      mechanism(s) by which SRCAP regulates transcription. These studies indicate that
      the N-terminal region of SRCAP, which contains five of the seven regions that
      comprise the ATPase domain, is not needed for activation of CREB-mediated
      transcription. SRCAP apparently has several domains that participate in the
      activation of transcription.

PMID- 11522780
TI  - Differential modulation of transcriptional activity of estrogen receptors by
      direct protein-protein interactions with the T cell factor family of
      transcription factors.
AB  - Two major signaling pathways, those triggered by estrogen (E(2)) and by the Wnt
      family, interact in the breast to cause growth and differentiation. The estrogen
      receptors ER(alpha) and ER(beta) are activated by binding E(2) and act as ligand
      dependent transcription factors. The effector for the Wnt family is the Tcf
      family of transcription factors. Both sets of transcription factors recognize
      discrete but different nucleotide sequences in the promoters of their target
      genes. By using transient transfections of reporter constructs for the
      osteopontin and thymidine kinase promoters in rat mammary cells, we show that Tcf
      4 antagonizes and Tcf-1 stimulates the effects of activated ER/E(2). For mutants
      of the former promoter, the stimulatory effects of ER(alpha)/E(2) can be made to
      be dependent on Tcf-1, and for the latter promoter the effects of the T cell
      factors (TCFs) are dependent on ER/E(2). Direct interaction between ERs and Tcfs
      either at the Tcf/ER(alpha)-binding site on the DNA or in the absence of DNA is
      established by gel retardation assays or by coimmunoprecipitation/biosensor
      methods, respectively. These results show that the two sets of transcription
      factors can interact directly, the interaction between ERs and Tcf-4 being
      antagonistic and that between ERs and Tcf-1 being synergistic on the activity of
      the promoters employed. Since Tcf-4 is the major Tcf family member in the breast,
      it is suggested that the antagonistic interaction is normally dominant in vivo in
      this tissue.

PMID- 11522781
TI  - Extracellular Toll-like receptor 2 region containing Ser40-Ile64 but not Cys30
      Ser39 is critical for the recognition of Staphylococcus aureus peptidoglycan.
AB  - Toll-like receptor 2 (TLR2) and CD14 function as pattern recognition receptors
      for bacterial peptidoglycan (PGN). TLRs and CD14 possess repeats of the leucine
      rich motif. To address the role of the extracellular domain of TLR2 in PGN
      signaling, we constructed CD14/TLR2 chimeras, in which residues 1-356 or 1-323 of
      CD14 were substituted for the extracellular domain of TLR2, and five deletion
      mutants of TLR2, in which the progressively longer regions of extracellular TLR2
      regions were deleted. PGN induced NF-kappaB activation in HEK293 cells expressing
      TLR2 but not in cells expressing CD14/TLR2 chimeras. The cells transfected with a
      deletion mutant TLR2(DeltaCys30-Ile64) as well as TLR2(DeltaCys30-Asp160) and
      TLR2(DeltaCys30-Asp305) failed to respond to PGN, indicating the importance of
      the TLR2 region Cys(30)-Ile(64). Although TLR2(DeltaCys30-Ser39) conferred cell
      responsiveness to PGN, the cells expressing TLR2(DeltaSer40-Ile64) failed to
      induce NF-kappaB activation. In addition, NF-kappaB activity elicited by PGN was
      significantly attenuated in the presence of synthetic peptide corresponding to
      the TLR2 region Ser(40)-Ile(64). From these results, we conclude that; 1) CD14
      cannot functionally replace the extracellular domain of TLR2 in PGN signaling; 2)
      the TLR2 region Cys(30)-Ser(39) is not required for PGN recognition; 3) the TLR2
      region containing Ser(40)-Ile(64) is critical for PGN recognition.

PMID- 11522782
TI  - Modification of Rab5 with a photoactivatable analog of geranylgeranyl
      diphosphate.
AB  - A photoprobe analog of geranylgeranyl diphosphate (2-diazo-3,3,3
      trifluoropropionyloxy-farnesyl diphosphate or DATFP-FPP) inhibits mevalonate
      dependent prenylation of in vitro translated Rab5 in rabbit reticulocyte lysate,
      suggesting that it competes for lipid binding to the Rab geranylgeranyl
      transferase. Modification of Rab5 with DATFP-FPP, demonstrated by gel mobility
      shift and Triton X-114 phase separation experiments, confirms that the enzyme
      uses the analog as a substrate. The sedimentation of DATFP-modified Rab5 as a
      larger mass complex on sucrose density gradients indicates that it binds to other
      factors in rabbit reticulocyte lysate. Most importantly, DATFP-Rab5 cross-links
      to these soluble factors upon exposure to UV light. Immunoprecipitation with
      antibodies raised against proteins known to interact with Rab5 reveals that the
      cross-linked complexes contain Rab escort protein and GDI-1. DATFP-Rab5 also
      associates with membranes in a guanosine-5'-O-(3-thiotriphosphate)-stimulated
      manner. However, although prenylated Rab5 can be cross-linked to two unknown
      membrane-associated factors by the chemical cross-linker disuccinimidyl suberate,
      these proteins fail to be UV cross-linked to membrane-bound DATFP-Rab5. These
      results strongly suggest that membrane-associated factors bind Rab5 through
      protein-protein interactions rather than protein-prenyl interactions. The
      modification of Rab5 with DATFP-FPP establishes a novel photoaffinity technique
      for the characterization of prenyl-binding sites.

PMID- 11522783
TI  - Structure of the induced antibacterial protein from tasar silkworm, Antheraea
      mylitta. Implications to molecular evolution.
AB  - The crystal structure of an antibacterial protein of immune origin (TSWAB),
      purified from tasar silkworm (Antheraea mylitta) larvae after induction by
      Escherichia coli infection, has been determined. This is the first insect
      lysozyme structure and represents induced lysozymes of innate immunity. The core
      structure of TSWAB is similar to c-type lysozymes and alpha-lactalbumins.
      However, TSWAB shows significant differences with respect to the other two
      proteins in the exposed loop regions. The catalytic residues in TSWAB are
      conserved with respect to the chicken lysozyme, indicating a common mechanism of
      action. However, differences in the noncatalytic residues in the substrate
      binding groove imply subtle differences in the specificity and the level of
      activity. Thus, conformational differences between TSWAB and chicken lysozyme
      exist, whereas functional mechanisms appear to be similar. On the other hand,
      alpha-lactalbumins and c-type lysozymes exhibit drastically different functions
      with conserved molecular conformation. It is evident that a common molecular
      scaffold is exploited in the three enzymes for apparently different physiological
      roles. It can be inferred on the basis of the structure-function comparison of
      these three proteins having common phylogenetic origin that the conformational
      changes in a protein are minimal during rapid evolution as compared with those in
      the normal course of evolution.

PMID- 11522784
TI  - GTPgammaS regulation of a 12-transmembrane guanylyl cyclase is retained after
      mutation to an adenylyl cyclase.
AB  - DdGCA is a Dictyostelium guanylyl cyclase with a topology typical for mammalian
      adenylyl cyclases containing 12 transmembrane-spanning regions and two cyclase
      domain. In Dictyostelium cells heterotrimeric G-proteins are essential for
      guanylyl cyclase activation by extracellular cAMP. In lysates, guanylyl cyclase
      activity is strongly stimulated by guanosine 5'-3-O-(thio) triphosphate
      (GTPgammaS), which is also a substrate of the enzyme. DdGCA was converted to an
      adenylyl cyclase by introducing three point mutations. Expression of the obtained
      DdGCA(kqd) in adenylyl cyclase-defective cells restored the phenotype of the
      mutant. GTPgammaS stimulated the adenylyl cyclase activity of DdGCA(kqd) with
      properties similar to those of the wild-type enzyme (decrease of K(m) and
      increase of V(max)), demonstrating that GTPgammaS stimulation is independent of
      substrate specificity. Furthermore, GTPgammaS activation of DdGCA(kqd) is
      retained in several null mutants of Galpha and Gbeta proteins, indicating that
      GTPgammaS activation is not mediated by a heterotrimeric G-protein but possibly
      by a monomeric G-protein.

PMID- 11522785
TI  - Discovery and structure of a potent and highly specific blocker of insect calcium
      channels.
AB  - We have isolated a novel family of insect-selective neurotoxins that appear to be
      the most potent blockers of insect voltage-gated calcium channels reported to
      date. These toxins display exceptional phylogenetic specificity, with at least a
      10,000-fold preference for insect versus vertebrate calcium channels. The
      structure of one of the toxins reveals a highly structured, disulfide-rich core
      and a structurally disordered C-terminal extension that is essential for channel
      blocking activity. Weak structural/functional homology with omega-agatoxin-IVA/B,
      the prototypic inhibitor of vertebrate P-type calcium channels, suggests that
      these two toxin families might share a similar mechanism of action despite their
      vastly different phylogenetic specificities.

PMID- 11522786
TI  - Characterization of glucokinase-binding protein epitopes by a phage-displayed
      peptide library. Identification of 6-phosphofructo-2-kinase/fructose-2,6
      bisphosphatase as a novel interaction partner.
AB  - The low affinity glucose-phosphorylating enzyme glucokinase shows the phenomenon
      of intracellular translocation in beta cells of the pancreas and the liver. To
      identify potential binding partners of glucokinase by a systematic strategy,
      human beta cell glucokinase was screened by a 12-mer random peptide library
      displayed by the M13 phage. This panning procedure revealed two consensus motifs
      with a high binding affinity for glucokinase. The first consensus motif,
      LSAXXVAG, corresponded to the glucokinase regulatory protein of the liver. The
      second consensus motif, SLKVWT, showed a complete homology to the bifunctional
      enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK-2/FBPase-2),
      which acts as a key regulator of glucose metabolism. Through yeast two-hybrid
      analysis it became evident that the binding of glucokinase to PFK-2/FBPase-2 is
      conferred by the bisphosphatase domain, whereas the kinase domain is responsible
      for dimerization. 5'-Rapid amplification of cDNA ends analysis and Northern blot
      analysis revealed that rat pancreatic islets express the brain isoform of PFK
      2/FBPase-2. A minor portion of the islet PFK-2/FBPase-2 cDNA clones comprised a
      novel splice variant with 8 additional amino acids in the kinase domain. The
      binding of the islet/brain PFK-2/ FBPase-2 isoform to glucokinase was comparable
      with that of the liver isoform. The interaction between glucokinase and PFK
      2/FBPase-2 may provide the rationale for recent observations of a fructose-2,6
      bisphosphate level-dependent partial channeling of glycolytic intermediates
      between glucokinase and glycolytic enzymes. In pancreatic beta cells this
      interaction may have a regulatory function for the metabolic stimulus-secretion
      coupling. Changes in fructose-2,6-bisphosphate levels and modulation of PFK
      2/FBPase-2 activities may participate in the physiological regulation of
      glucokinase-mediated glucose-induced insulin secretion.

PMID- 11522787
TI  - The muscle-specific protein phosphatase PP1G/R(GL)(G(M))is essential for
      activation of glycogen synthase by exercise.
AB  - In skeletal muscle both insulin and contractile activity are physiological
      stimuli for glycogen synthesis, which is thought to result in part from the
      dephosphorylation and activation of glycogen synthase (GS). PP1G/R(GL)(G(M)) is a
      glycogen/sarcoplasmic reticulum-associated type 1 phosphatase that was originally
      postulated to mediate insulin control of glycogen metabolism. However, we
      recently showed (Suzuki, Y., Lanner, C., Kim, J.-H., Vilardo, P. G., Zhang, H.,
      Jie Yang, J., Cooper, L. D., Steele, M., Kennedy, A., Bock, C., Scrimgeour, A.,
      Lawrence, J. C. Jr., L., and DePaoli-Roach, A. A. (2001) Mol. Cell. Biol. 21,
      2683-2694) that insulin activates GS in muscle of R(GL)(G(M)) knockout (KO) mice
      similarly to the wild type (WT). To determine whether PP1G is involved in
      glycogen metabolism during muscle contractions, R(GL) KO and overexpressors (OE)
      were subjected to two models of contraction, in vivo treadmill running and in
      situ electrical stimulation. Both procedures resulted in a 2-fold increase in the
      GS -/+ glucose-6-P activity ratio in WT mice, but this response was completely
      absent in the KO mice. The KO mice, which also have a reduced GS activity
      associated with significantly reduced basal glycogen levels, exhibited impaired
      maximal exercise capacity, but contraction-induced activation of glucose
      transport was unaffected. The R(GL) OE mice are characterized by enhanced GS
      activity ratio and an approximately 3-4-fold increase in glycogen content in
      skeletal muscle. These animals were able to tolerate exercise normally.
      Stimulation of GS and glucose uptake following muscle contraction was not
      significantly different as compared with WT littermates. These results indicate
      that although PP1G/R(GL) is not necessary for activation of GS by insulin, it is
      essential for regulation of glycogen metabolism under basal conditions and in
      response to contractile activity, and may explain the reduced muscle glycogen
      content in the R(GL) KO mice, despite the normal insulin activation of GS.

PMID- 11522788
TI  - Mapping CooA.RNA polymerase interactions. Identification of activating regions 2
      and 3 in CooA, the co-sensing transcriptional activator.
AB  - CooA is a CO-sensing protein that activates the transcription of genes encoding
      the CO-oxidation (coo) regulon, whose polypeptide products are required for
      utilizing CO as an energy source in Rhodospirillum rubrum. CooA binds to a
      position overlapping the -35 element of the P(cooF) promoter, similar to the
      arrangement of class II CRP (cAMP receptor protein)- and FNR (fumarate and
      nitrate reductase activator protein)-dependent promoters when expressed in
      Escherichia coli. Gain-of-function CooA variants were isolated in E. coli
      following mutagenesis of the portion of cooA encoding the effector-binding
      domain. Some of the mutations affect regions of CooA that are homologous to the
      activating regions (AR2 and AR3) previously identified in CRP and FNR, whereas
      others affect residues that lie in a region of CooA between AR2 and AR3. These
      CooA variants are comparable to wild-type (WT) CooA in DNA binding affinity in
      response to CO but differ in transcription activation, presumably because of
      altered interactions with E. coli RNA polymerase. Based on predictions of
      similarity to CRP and FNR, loss-of-function CooA variants were obtained in the
      AR2 and AR3 regions that have minimal transcriptional activity, yet have WT-like
      DNA binding affinities in response to CO. This study demonstrates that WT CooA
      contains AR2- and AR3-like surfaces that are required for optimal transcription
      activation.

PMID- 11522789
TI  - A mitogen-activated protein kinase-dependent signaling pathway in the activation
      of platelet integrin alpha IIbbeta3.
AB  - We have recently shown that the platelet integrin alpha(IIb)beta(3) is activated
      by von Willebrand factor (vWF) binding to its platelet receptor, glycoprotein Ib
      IX (GPIb-IX), via the protein kinase G (PKG) signaling pathway. Here we show that
      GPIb-IX-mediated activation of integrin alpha(IIb)beta(3) is inhibited by
      dominant negative mutants of Raf-1 and MEK1 in a reconstituted integrin
      activation model in Chinese hamster ovary (CHO) cells and that the integrin
      dependent platelet aggregation induced by either vWF or low dose thrombin is
      inhibited by MEK inhibitors PD98059 and U0126. Thus, mitogen-activated protein
      kinase (MAPK) pathway is important in GPIb-IX-dependent activation of platelet
      integrin alpha(IIb)beta(3). Furthermore, vWF binding to GPIb-IX induces
      phosphorylation of Thr-202/Tyr-204 of extracellular signal-regulated kinase 2
      (ERK2). GPIb-IX-induced ERK2 phosphorylation is inhibited by PKG inhibitors and
      enhanced by overexpression of recombinant PKG. PKG activators also induce ERK
      phosphorylation, indicating that activation of MAPK pathway is downstream from
      PKG. Thus, our data delineate a novel integrin activation pathway in which ligand
      binding to GPIb-IX activates PKG that stimulates MAPK pathway, leading to
      integrin activation.

PMID- 11522790
TI  - A mutant form of JAB/SOCS1 augments the cytokine-induced JAK/STAT pathway by
      accelerating degradation of wild-type JAB/CIS family proteins through the SOCS
      box.
AB  - Cytokines exert biological functions by activating Janus tyrosine kinases (JAKs),
      and JAK inhibitors JAB (also referred to as SOCS1 and SSI1) and CIS3 (SOCS3) play
      an essential role in the negative regulation of cytokine signaling. We have found
      that transgenic (Tg) mice expressing a mutant JAB (F59D-JAB) exhibited a more
      potent STAT3 activation and a more severe colitis than did wild-type littermates
      after treatment with dextran sulfate sodium. We now find that there is a
      prolonged activation of JAKs and STATs in response to a number of cytokines in T
      cells from Tg mice with lck promoter-driven F59D-JAB. Overexpression of F59D-JAB
      also sustained activation of JAK2 in Ba/F3 cells. These data suggested that F59D
      JAB up-regulated STAT activity by sustaining JAK activation. To elucidate
      molecular mechanisms related to F59D-JAB, we analyzed the effects of F59D-JAB on
      the JAK/STAT pathway using the 293 cell transient expression system. We found
      that the C-terminal SOCS-box played an essential role in augmenting cytokine
      signaling by F59D-JAB. The SOCS-box interacted with the Elongin BC complex, and
      this interaction stabilized JAB. F59D-JAB induced destabilization of wild-type
      JAB, whereas overexpression of Elongin BC canceled this effect. Levels of
      endogenous JAB and CIS3 in T cells from F59D-JAB Tg-mouse were lower than in wild
      type mice. We propose that F59D-JAB destabilizes wild-type, endogenous JAB and
      CIS3 by chelating the Elongin BC complex, thereby sustaining JAK activation.

PMID- 11522791
TI  - Cloning and characterization of a novel mouse AP-2 transcription factor, AP
      2delta, with unique DNA binding and transactivation properties.
AB  - AP-2 transcription factors are sequence-specific DNA-binding proteins expressed
      in neural crest and other tissues during mammalian development. Three mammalian
      genes, AP-2alpha, AP-2beta, and AP-2gamma, have been reported previously. A
      partial predicted AP-2 gene was identified in tandem with AP-2beta on human
      chromosome 6p12-p21.1. The orthologous mouse gene, which we named Ap-2delta, was
      identified from a fetal mouse head cDNA library. Northern analysis revealed two
      transcripts in embryonic and newborn mouse brain, with markedly higher steady
      state levels in the former. The predicted Ap-2delta protein comprised 452 amino
      acids and was highly similar to other AP-2 proteins across the DNA-binding and
      dimerization domains. Ap-2delta formed homodimers and heterodimers in vitro,
      bound an optimized AP-2 consensus DNA sequence, and transactivated gene
      expression in eukaryotic cells. Ap-2delta dimers bound poorly to an AP-2 binding
      sequence from the human metallothionein IIa promoter in vitro, revealing a
      sequence specificity not previously observed among other AP-2 proteins. The PY
      motif and critical residues in the transactivation domain, which are highly
      conserved in the AP-2 family and believed necessary for transactivation, were
      divergent in Ap-2delta. The unique protein sequence and functional features of Ap
      2delta suggest mechanisms, besides tissue-specific AP-2 gene expression, for
      specific control of target gene activation.

PMID- 11522792
TI  - Functional analysis of Streptococcus pneumoniae MurM reveals the region
      responsible for its specificity in the synthesis of branched cell wall peptides.
AB  - The recently identified murMN operon of Streptococcus pneumoniae encodes enzymes
      involved in the synthesis of branched structured muropeptides of the pneumococcal
      cell wall peptidoglycan. Its inactivation was shown to cause production of a
      peptidoglycan composed exclusively of linear muropeptides and a virtually
      complete loss of resistance in penicillin-resistant strains. The studies
      described in this communication follow up these observations in several
      directions. The substrate of the MurM-catalyzed reaction (addition of alanine or
      serine) was identified as the lipid-linked N-acetylglucosamine-muramyl
      pentapeptide. Different murM alleles from several penicillin-resistant S.
      pneumoniae strains, each with a characteristic branched peptide pattern, were
      cloned into pLS578, a pneumococcal plasmid capable of replicating in S.
      pneumoniae, and transformed into the penicillin-susceptible laboratory strain
      R36A. All transformants remained penicillin-susceptible; however, their cell wall
      composition changed in directions corresponding to the muropeptide pattern of the
      strain from which the murM allele was derived. This suggests that the muropeptide
      composition of the pneumococcal cell walls is determined by the particular murM
      allele carried by the cells. A 30-amino acid long sequence within the MurM
      protein was shown to be the main determinant of the specificity of the reaction
      (addition of alanine versus serine).

PMID- 11522793
TI  - Novel betacellulin derivatives. Separation of the differentiation activity from
      the mitogenic activity.
AB  - Betacellulin (BTC) is a member of the epidermal growth factor family. It has two
      biological activities: mitogenic activity in fibroblasts and vascular smooth
      muscle cells, and differentiation activity for the differentiation of pancreatic
      acinar AR42J cells into insulin-secreting cells. The previous finding that
      recombinant BTC promotes the neogenesis of beta-cells in a mouse model supports
      the possibility that BTC is a therapeutic protein. However, the mitogenic
      activity of BTC may not be needed for differentiation into beta-cells and may
      cause a side effect in clinical use. We prepared several derivatives of BTC to
      segregate the two activities, to decrease the mitogenic activity, and to maintain
      the differentiation activity. We succeeded in obtaining BTC derivatives
      segregated by the two biological activities by preparing truncated-type
      derivatives. A derivative of BTC, BTC24-76, with a truncated N-terminal 23 amino
      acids and C-terminal 4 amino acids, was 2.5-fold more active in differentiation
      and had one-tenth of the mitogenic activity. The derivatives described in the
      present study should be helpful in future applications as therapeutic proteins
      and in basic research for discovery of a BTC-specific receptor.

PMID- 11522794
TI  - Role of the cytoskeleton in mediating cAMP-dependent protein kinase inhibition of
      the epithelial Na+/H+ exchanger NHE3.
AB  - The Na(+)/H(+) exchanger NHE3 isoform mediates the entry of Na(+) into epithelial
      cells of the kidney and gastrointestinal tract. Hormones and pharmacological
      agents that activate cAMP-dependent protein kinase A (PKA) are potent inhibitors
      of native and ectopically expressed NHE3 in epithelial and Chinese hamster ovary
      AP-1 cells, respectively. Previous studies have shown that acute inhibition is
      coupled to direct phosphorylation of the exchanger, but this only partly accounts
      for the observed effects. In this report, we show that inhibition of NHE3
      activity by forskolin, an activator of adenylate cyclase, occurs without changes
      in surface expression of the exchanger but is associated with altered
      cytoskeletal structure. This effect resembles that obtained with cytochalasin D
      or latrunculin B, actin disrupting agents that also inhibit NHE3. Such
      similarities prompted us to further investigate the relationship between PKA
      induced inhibition of the exchanger and changes in the actin cytoskeleton.
      Inhibition of NHE3 by cytochalasin D does not require PKA, because the inhibitory
      effect is preserved in a mutant NHE3 that is not phosphorylated by PKA and in
      cells pretreated with the PKA inhibitor H89. In contrast, involvement of actin in
      the effect of cAMP on the exchanger is supported by the following observations:
      (i) jasplakinolide, an F-actin stabilizer, prevents the inhibition caused by
      forskolin, and (ii) constitutively active forms of RhoA and Rho kinase interfere
      with actin disruption by forskolin and also decrease inhibition of the
      transporter. These results suggest that reorganization of the cytoskeleton by PKA
      is involved in mediating inhibition of NHE3.

PMID- 11522795
TI  - Accelerated metabolism and exclusion of 4-hydroxynonenal through induction of
      RLIP76 and hGST5.8 is an early adaptive response of cells to heat and oxidative
      stress.
AB  - To explore the role of lipid peroxidation (LPO) products in the initial phase of
      stress mediated signaling, we studied the effect of mild, transient oxidative or
      heat stress on parameters that regulate the cellular concentration of 4
      hydroxynonenal (4-HNE). When K562 cells were exposed to mild heat shock (42
      degrees C, 30 min) or oxidative stress (50 microM H2O2, 20 min) and allowed to
      recover for 2 h, there was a severalfold induction of hGST5.8, which catalyzes
      the formation of glutathione-4-HNE conjugate (GS-HNE), and RLIP76, which mediates
      the transport of GS-HNE from cells (Awasthi, S., Cheng, J., Singhal, S. S.,
      Saini, M. K., Pandya, U., Pikula, S., Bandorowicz-Pikula, J., Singh, S. V.,
      Zimniak, P., and Awasthi, Y. C. (2000) Biochemistry 39, 9327-9334). Enhanced LPO
      was observed in stressed cells, but the major antioxidant enzymes and HSP70
      remained unaffected. The stressed cells showed higher GS-HNE-conjugating activity
      and increased efflux of GS-HNE. Stress-pre-conditioned cells with induced hGST5.8
      and RLIP76 acquired resistance to 4-HNE and H2O2-mediated apoptosis by
      suppressing a sustained activation of c-Jun N-terminal kinase and caspase 3. The
      protective effect of stress pre-conditioning against apoptosis was abrogated by
      coating the cells with anti-RLIP76 IgG, which inhibited the efflux of GS-HNE from
      cells, indicating that the cells acquired resistance to apoptosis by metabolizing
      and excluding 4-HNE at a higher rate. Induction of hGST5.8 and RLIP76 by mild,
      transient stress and the resulting resistance of stress-pre-conditioned cells to
      apoptosis appears to be a general phenomenon since it was not limited to K562
      cells but was also evident in lung cancer cells, H-69, H-226, human leukemia
      cells, HL-60, and human retinal pigmented epithelial cells. These results
      strongly suggest a role of LPO products, particularly 4-HNE, in the initial phase
      of stress mediated signaling.

PMID- 11522796
TI  - The transcription factor C/EBPbeta is essential for inducible expression of the
      cox-2 gene in macrophages but not in fibroblasts.
AB  - Cyclooxygenase-2 (COX-2) is the rate-limiting enzyme for the inducible synthesis
      of prostaglandins, and its up-regulated activity is thought to play a
      pathological role in diseases such as inflammatory bowel disease, rheumatoid
      arthritis, and cancer. Regulation of COX-2 expression is complex and appears to
      involve diversified mechanisms in different cell types and conditions. Here we
      make use of immortalized macrophages and fibroblasts that we have generated from
      C/EBPbeta-deficient mice to directly test and compare the specific role played by
      this factor in inducible COX-2 expression in these two cell types. We could
      demonstrate that COX-2 mRNA induction and promoter activity were profoundly
      impaired in C/EBPbeta(-/-) macrophages and could be rescued by expression of
      C/EBPbeta. The obligatory role of C/EBPbeta in COX-2 expression appeared to be
      mediated exclusively by the C/EBP element located at positions -138/-130 of the
      murine cox-2 promoter, and did not involve altered activity at the level of the
      other promoter elements described previously (the -402/-392 NF-kappaB site, the 
      59/-48 CRE/E box element, and a potential second C/EBP site located at positions 
      93/-85). In contrast, COX-2 induction was completely normal in C/EBPbeta
      deficient fibroblasts, thus highlighting the diversity of cell-specific molecular
      mechanisms in determining inducible COX-2 expression and prostaglandins
      production.

PMID- 11522797
TI  - Biochemical and structural assessment of the 1-N-azasugar GalNAc-isofagomine as a
      potent family 20 beta-N-acetylhexosaminidase inhibitor.
AB  - Azasugar inhibitors of the isofagomine class are potent competitive inhibitors of
      configuration-retaining beta-glycosidases. This potency results from the
      formation of a strong electrostatic interaction between a protonated endocyclic
      nitrogen at the "anomeric" center of the inhibitor and the catalytic nucleophile
      of the enzyme. Although the majority of retaining beta-glycosidases use a
      mechanism involving a carboxylate residue as a nucleophile, Streptomyces plicatus
      beta-N-acetylhexos-aminidase (SpHEX) and related family 20 glycosidases lack such
      a catalytic residue and use instead the carbonyl oxygen of the 2-acetamido group
      of the substrate as a nucleophile to "attack" the anomeric center. Thus, a strong
      electrostatic interaction between the inhibitor and enzyme is not expected to
      occur; nonetheless, the 1-N-azasugar (2R,3R,4S,5R)-2-acetamido-3,4-dihydroxy-5
      hydroxymethyl-piperidinium hydrochloride (GalNAc-isofagomine.HCl), which was
      synthesized and assayed for its ability to inhibit SpHEX, was found to be a
      potent competitive inhibitor of the enzyme (K(i) = 2.7 microm). A
      crystallographic complex of GalNAc-isofagomine bound to SpHEX was solved and
      refined to 1.75 A and revealed that the lack of a strong electrostatic
      interaction between the "anomeric" center of GalNAc-isofagomine and SpHEX is
      compensated for by a novel 2.8-A hydrogen bond formed between the equatorial
      proton of the endocyclic nitrogen of the azasugar ring and the carboxylate of the
      general acid-base residue Glu-314 of SpHEX. This interaction appears to
      contribute to the unexpected potency of GalNAc-isofagomine toward SpHEX.

PMID- 11522798
TI  - An accessible hydrophobic surface is a key element of the molecular chaperone
      action of Atp11p.
AB  - Atp11p is a soluble protein of mitochondria that binds unassembled beta subunits
      of the F(1)-ATPase and prevents them from aggregating in the matrix. In this
      report, we show that Atp11p protects the insulin B chain from aggregating in
      vitro and therefore acts as a molecular chaperone. The chaperone action of Atp11p
      is mediated by hydrophobic interactions. An accessible hydrophobic surface in
      Atp11p was identified with the environment-sensitive fluorescent probe 1,1'-bis(4
      anilino-5-napththalenesulfonic acid (bis-ANS). The spectral changes of bis-ANS in
      the presence of Atp11p indicate that the probe binds to a nonpolar region of the
      protein. Furthermore, the dye quenches the fluorescence of Atp11p tryptophan
      residues in a concentration-dependent manner. Although up to three molecules of
      bis-ANS can bind cooperatively to Atp11p, the binding of only one dye molecule is
      sufficient to virtually eliminate the chaperone activity of the protein.

PMID- 11522799
TI  - MyoD can induce cell cycle arrest but not muscle differentiation in the presence
      of dominant negative SWI/SNF chromatin remodeling enzymes.
AB  - Cell cycle arrest is critical for muscle differentiation, and the two processes
      are closely coordinated but temporally separable. SWI/SNF complexes are ATP
      dependent chromatin-remodeling enzymes that have been shown to be required for
      muscle differentiation in cell culture and have also been reported to be required
      for Rb-mediated cell cycle arrest. We therefore looked more closely at how
      SWI/SNF enzymes affect the events that occur during MyoD-induced myogenesis,
      namely, cell cycle regulation and muscle-specific gene expression, in cells that
      inducibly express dominant negative versions of Brahma (BRM) and Brahma-related
      gene 1 (BRG1), the ATPase subunits of two distinct SWI/SNF complexes. Although
      dominant negative BRM and BRG1 inhibited expression of every muscle-specific
      regulator and structural gene assayed, there was no effect on MyoD-induced
      activation of cell cycle regulatory proteins, and thus, cells arrested normally.
      In particular, in the presence or absence of dominant negative BRM or BRG1, MyoD
      was able to activate expression of p21, cyclin D3, and Rb, all of which are
      critical for cell cycle withdrawal in the G1/G0 phase of the cell cycle. These
      findings suggest that at least one basis for the distinct mechanisms that
      regulate cessation of cell proliferation and muscle-specific gene expression
      during muscle differentiation is that SWI/SNF-mediated chromatin-remodeling
      enzymes are required only for the latter.

PMID- 11522800
TI  - Attachment bonds between adult daughters and their older mothers: associations
      with contemporary caregiving.
AB  - This study examined associations between attachment bonds and the care that
      daughters were providing to their community-dwelling mothers. Adult daughters (40
      African American, 40 European American) completed assessments of adult
      attachment, instrumental and emotional caregiving, and caregiver burden. The
      author performed hierarchical linear regressions to examine the relationships
      between attachment dimensions (Security and Anxiety) and the provision of
      instrumental and emotional care. Both attachment dimensions were unrelated to the
      provision of instrumental care. In contrast, high scores on the Security
      dimension and low scores on the Anxiety dimension were associated with the
      provision of more emotional care to mothers. A final analysis revealed that high
      scores on the Security dimension were associated with less caregiver burden.
      These results suggest that practical care that daughters provide to their mothers
      may be independent of attachment patterns within the child-parent relationship,
      whereas affective, discretionary care may be promoted or hindered by attachment
      patterns. Moreover, the stress of caregiving may be mediated by a more secure
      attachment bond. The potential impact of adult attachment patterns has
      implications for both family intervention and public policy, given that more
      families are expected to participate in caregiving in coming decades.

PMID- 11522801
TI  - Sensory impairments and subjective well-being among aged African American
      persons.
AB  - The limited number of studies concerning the prevalence of hearing loss and
      vision impairment and their causes, and the lack of strategies to prevent or
      treat the deleterious effects of hearing loss and vision impairment, point to a
      significant gap in the knowledge base concerning aged minority populations. This
      cross-sectional study evaluated the relationship between vision and hearing
      impairment and psychological well-being among a sample of 988 elderly African
      American persons. Fair or poor vision or hearing was reported for 36.5% and 26%
      of our sample, respectively. Reported prevalence rates for these impairments are
      considerably higher than rates previously documented in comparable studies of
      elderly people conducted in general (i.e., predominantly White) populations.
      Eighty-four percent of our study participants attempted to improve their vision
      through the use of eyeglasses. By contrast, only 4.3% of individuals in the study
      who described their hearing as poor reported using hearing aids. Using
      multivariate analysis and other related variables that have previously been
      identified as common predictors of psychological well-being, the findings of this
      study suggest that poor vision is independently associated with a lower level of
      psychological well-being among aged African Americans even after adjusting for
      sociodemographic characteristics, functional limitations, perceived health
      status, and cognition. Poor hearing was also found to be associated with a lower
      level of psychological well-being; however, this relationship was not independent
      but was mediated by the effect of hearing on functional status. These data
      indicate considerable potential for improved psychological well-being for African
      American elderly people through visual and audiological rehabilitation.

PMID- 11522802
TI  - Development of a pain attitudes questionnaire to assess stoicism and cautiousness
      for possible age differences.
AB  - This study aimed to develop a pain attitudes questionnaire (PAQ) and examine its
      reliability and validity for use in assessing the constructs of stoicism and
      cautiousness relevant to pain perception. The questionnaire was administered to
      373 healthy community-dwelling individuals who were subsequently divided into
      four age groups to test for differences in stoicism and cautiousness, two
      attitudes that have previously been claimed to influence pain perception and
      report among older adults. Factor analysis revealed that two dimensions of
      stoicism and two dimensions of cautiousness are measured by the scale, with
      reticence and superiority characterizing the first construct and self-doubt and
      reluctance characterizing the second. There was support for the scale's
      reliability and validity. Age-related increase in degree of reticence to pain,
      self-doubt, and reluctance to label a sensation as painful was found, emphasizing
      the need for careful consideration of pain attitudes in older patients who may
      underreport their pain symptoms.

PMID- 11522803
TI  - Older adults' acceptance of psychological and pharmacological treatments for
      depression.
AB  - Two hundred participants aged 65 and older recruited from 4 different family
      medicine clinics rated the acceptability of 3 different treatments for geriatric
      depression: (a) cognitive therapy (CT), (b) cognitive bibliotherapy (CB), and (c)
      antidepressant medication (AM). Results showed that the acceptability of the
      treatments is a function of the severity of the symptoms of the depressed patient
      to whom they would be applied. CT and CB were rated as more acceptable than AM
      when patient symptoms were mild to moderate. However, CT was more acceptable than
      both CB and AM when patient symptoms were described as severe. Acceptability
      ratings were not related to the raters' own depressive symptoms. The practical
      implications of these results are discussed.

PMID- 11522804
TI  - Education and the risk of Alzheimer's disease: findings from the study of
      dementia in Swedish twins.
AB  - The association between dementia and education was studied in 143 twin pairs
      discordant for dementia, using a matched-pair design, and in 221 dementia cases
      and 442 unrelated controls from the same twin registry, using a case-control
      design. Low education was defined as 6 years or less of schooling. Case-control
      analyses with prevalent cases showed low education to be a risk for Alzheimer's
      disease but not dementia in general. Low education did not significantly predict
      incident cases. In the matched-pairs analysis, which controls for genetic and
      other familial influences, differences in education between demented twins and
      twin partners were not statistically significant. However, for Alzheimer's
      disease, odds ratios resulting from matched pairs and case-control analyses were
      similar. Twins' comparative reports about intellectual involvement earlier in
      their lives suggest a long-standing difference on this dimension, with less
      involvement by the twin who became demented.

PMID- 11522805
TI  - A longitudinal study of the relationship between levels of depression among
      persons with Alzheimer's disease and levels of depression among their family
      caregivers.
AB  - The purpose of this study was to examine the effects, over time, of depressive
      symptoms in persons with Alzheimer's disease on depression in their family
      caregivers. In a sample of 353 patients and caregivers, multilevel longitudinal
      analysis was used to accommodate an observational design in which the number of
      observation points and the intervals between points varied across caregivers. The
      rate of change (increase) in caregiver depression was predicted by the rate of
      change (increase) in patient depressive symptoms and by increase in patient
      dependency in instrumental activities of daily living (ADLs). Acceleration of the
      increase in caregiver depression was predicted by acceleration in patient
      dependency in instrumental and basic ADLs but not by acceleration in patient
      depressive symptoms. These findings indicate the importance of measuring the rate
      and acceleration of change in patient characteristics in order to understand
      caregiver depression. They also support early interventions for caregivers.

PMID- 11522806
TI  - A 5-year retrospective examination of cognitive screening test stages in normal
      older adults and patients with Alzheimer's disease: the Tajiri project.
AB  - One conception of aging and cognitive deterioration is that cognitive decline
      becomes common with age, and dementia may be regarded as one extreme of the
      continuum. An alternative conception is that the cognitive process is spared by
      the aging process itself and that cognitive functioning of normal older adults
      and those with slight cognitive impairment, a CDR (Clinical Dementia Rating)
      score of 0.5 (suspected dementia), should be different. We examined changes in
      the screening test performances of 170 older adults over a 5-year period and
      found the following: (a) The CDR 0 (normal) participants did not show remarkable
      changes even in the older groups and (b) the subitems of orientation, memory, and
      so forth were useful for distinguishing normal older adults from early
      Alzheimer's disease patients. The results support the idea that dementia is
      better conceptualized as an age-related than as an "aging-related" disorder and
      that a CDR score of 0.5 should be considered very mild Alzheimer's disease.

PMID- 11522807
TI  - Self-efficacy and the progression of functional limitations and self-reported
      disability in older adults with knee pain.
AB  - OBJECTIVES: The prospective relationships between self-efficacy beliefs, in
      conjunction with measures of knee pain and knee strength, and subsequent decline
      in both physical performance and self-reported disability among older adults with
      knee pain were examined. METHODS: In this prospective epidemiological trial, 480
      men and women aged 65 years and older who had knee pain on most days of the week
      and difficulty with daily activity were followed for 30 months. RESULTS: There
      was a significant interaction of baseline self-efficacy with baseline knee
      strength in predicting both self-reported disability and stair climb performance.
      Participants who had low self-efficacy and low strength at baseline had the
      largest 30-month decline in these outcomes. DISCUSSION: These data underscore the
      important role that self-efficacy beliefs play in understanding functional
      decline with chronic disease and aging. Self-efficacy beliefs appear to be most
      important to functional decline in older adults when they are challenged by
      muscular weakness in the lower extremities.

PMID- 11522808
TI  - Race differences in cognitive functioning among older adults.
AB  - OBJECTIVES: Explaining race differences in cognitive functioning in later life
      continues to challenge researchers. This study was an attempt to incorporate the
      clinical literature, emphasizing biological correlates of cognitive functioning,
      and the social research literature, emphasizing social inequalities and
      consequent health outcomes, in the examination of sources of race differences in
      cognitive functioning in older adults. METHODS: With data from Wave 1 of the
      Assets and Health Dynamics of the Oldest Old survey, the authors used structural
      equation models (LISREL 8.30) to estimate the direct effects of race on cognitive
      functioning and indirect effects through social and biological risk factors for
      the total sample (N = 5,955). RESULTS: Race had a direct association with
      cognitive functioning. Race also had indirect effects on cognitive functioning
      through social risk factors-education and health insurance. There did not appear
      to be indirect effects of race through biological risk factors. DISCUSSION: The
      direct and indirect effects of race through social risk factors attest to the
      importance of examining different ways through which race can influence cognitive
      functioning of older adults. This research also emphasizes the need for
      researchers to investigate more closely race differences in dimensions of
      cognitive functioning and cognitive functioning over time.

PMID- 11522809
TI  - Duration or disadvantage? Exploring nativity, ethnicity, and health in midlife.
AB  - OBJECTIVES: This study examined nativity as a risk factor for poor physical and
      emotional health for an ethnically diverse population making the transition into
      retirement. The authors addressed whether the health disadvantage observed for
      immigrants lessens with increased time spent in the country (supporting theories
      of assimilation) or increases with duration of residence (supporting theories of
      cumulative disadvantage). METHODS: The sample was drawn from Waves 1 and 2 of the
      Health and Retirement Study (HRS), an in-depth economic, social, and health
      database of persons in midlife and beyond. The analyses were restricted to 9,912
      native-born and 1,031 foreign-born individuals. RESULTS: The data revealed that
      after socioeconomic factors were controlled, foreign-born individuals were at
      higher risk of poor emotional health than their native-born counterparts.
      Although aging immigrants displayed worse health than the native-born population,
      this disadvantage was mediated by duration of residence (young age at migration)
      and socioeconomic incorporation. DISCUSSION: These findings extend our
      understanding of nativity and duration as risk factors for poor physical and
      emotional health. Immigrants may overcome the nativity disadvantages found for
      emotional distress with increased duration of residence, but the pattern becomes
      more complicated with the inclusion of race and Hispanic ethnicity.

PMID- 11522810
TI  - The relative effect of Alzheimer's disease and related dementias, disability, and
      comorbidities on cost of care for elderly persons.
AB  - OBJECTIVES: Our primary objectives were (a) to determine the relative impact of
      Alzheimer's disease and related dementias (ADRD), disability, and common comorbid
      health conditions on the cost of caring for community-dwelling elderly person and
      (b) to determine whether ADRD serves as an effect modifier for the effect of
      disability and common comorbidities on costs. METHODS: Participants were drawn
      from community respondents to the 1994 National Long Term Care Survey. The
      authors compared total cost of caring for persons without ADRD with that of those
      who had moderate and severe ADRD. Using regression analysis, the author
      identified the adjusted effect of ADRD, limitations in activities of daily living
      (ADLs), and common comorbidities on total costs. RESULTS: Persons with severe
      ADRD had higher median total costs ($10,234) than did persons with moderate ADRD
      ($4,318) and those without ADRD ($2,268, p <.001). However, disability measured
      by ADL limitations was a more important predictor of total cost than was ADRD
      status in both stratified and multivariate analyses. Comorbidities such as heart
      attack, stroke, and chronic obstructive pulmonary disease also increased costs.
      Severe ADRD was an effect modifier for ADL limitations, increasing the positive
      impact of disability on total costs among persons with severe ADRD, but not for
      comorbidities. DISCUSSION: Disability, severe ADRD, and comorbidity all had
      independent effects that increased total costs. Thus, any risk adjustment
      procedure should account for disability and comorbidity and not just ADRD status.

PMID- 11522811
TI  - Educational differences in the prevalence of mobility disability in old age: the
      dynamics of incidence, mortality, and recovery.
AB  - OBJECTIVES: Older people with less education have substantially higher prevalence
      rates of mobility disability. This study aimed to establish the relative
      contributions of incidence, recovery rates, and death to prevalence differences
      in mobility disability associated with educational status. METHODS: Data were
      from 3 sites of the Established Populations for Epidemiological Study of the
      Elderly, covering 8,871 people aged 65-84 years who were followed for up to 7
      years. Participants were classified on years of education received and as
      disabled if they needed help or were unable to walk up or down stairs or walk
      half a mile. A Markov model computed relative risks, adjusting for the effects of
      repeated observations on the same individuals. RESULTS: Differences between
      education groups in person-years lived with disability were large. The relative
      risk of incident disability in men with 0-7 years of education (vs. those with 12
      or more years) was 1.65 (95% CI = 1.37-1.97) and in women was 1.70 (95% CI = 1.15
      2.53). Both recovery risks and risks of death in those with disability were not
      significantly different across education groups in either gender. DISCUSSION:
      Higher incidence of disability is the main contributor to the substantially
      higher prevalence of disability in older people of lower socioeconomic status.
      Efforts to reduce the disparity in disability rates by socioeconomic status in
      old age should focus mainly on preventing disability, because differences in the
      course of mobility disability after onset appear to play a limited role in the
      observed prevalence disparities.

PMID- 11522812
TI  - Targeting risk for unmet need: not enough help versus no help at all.
AB  - OBJECTIVES: This study examined factors associated with unmet need for care among
      persons aged 18 and older who need help with daily living tasks. The analysis
      focused on two types of unmet need: not enough (or inadequate) help and no help
      at all. METHODS: The authors used multinomial logistic regression to examine
      differences between persons with long-term care needs who (a) had all their needs
      met; (b) received inadequate help; and (c) received no help at all. Data were
      from the Adult Followback to the National Health Interview Survey on Disability
      (NHIS-D) for 1994 and 1995. RESULTS: The determinants of inadequate care versus
      no care differed with respect to age, gender, level of impairment, and insurance
      status. Whereas age and gender were important in determining inadequate care,
      insurance coverage and availability of social support were key factors related to
      a situation of no care. DISCUSSION: The present study demonstrates that the
      characteristics of groups reporting inadequate care versus no care, and the
      factors associated with these situations, are quite different. Nevertheless, the
      most important demographic risk factors for both types of unmet need mirror
      demographic groups currently on the increase in the U.S. population.

PMID- 11522813
TI  - Childlessness and the psychological well-being of older persons.
AB  - OBJECTIVES: Rapid growth in the size of the childless elderly population has
      prompted concerns about the negative effects of childlessness on psychological
      well-being. This study adds to this line of inquiry by examining the effects of
      childlessness on two important dimensions of elderly persons' psychological well
      being: loneliness and depression. METHODS: Using the 1993 Asset and Health
      Dynamics Among the Oldest Old data set, the authors estimated logistic and
      ordinary least squares regression models of psychological well-being for a
      nationally representative sample of people aged 70 and older (N = 6,517).
      RESULTS: Childlessness per se did not significantly increase the prevalence of
      loneliness and depression at advanced ages, net of other factors. There also was
      no statistical evidence for the hypothesis that childlessness increases
      loneliness and depression for divorced, widowed, and never married elderly
      persons. Sex, however, altered how childlessness and marital status influenced
      psychological well-being. Divorced, widowed, and never married men who were
      childless had significantly higher rates of loneliness compared with women in
      comparable circumstances; divorced and widowed men who were childless also had
      significantly higher rates of depression than divorced and widowed women.
      DISCUSSION: The findings suggest that it is important to understand the
      consequences of childlessness in the context of marital status and sex.

PMID- 11522814
TI  - A critical evaluation of differential display as a tool to identify genes
      involved in legume nodulation: looking back and looking forward.
AB  - Screening for differentially expressed genes is a straightforward approach to
      study the molecular basis of a biological system. In the last 10 years,
      differential screening technology has evolved rapidly and currently high
      throughput tools for genome-wide transcript profiling, such as expressed sequence
      tags and microarray analysis, are becoming widely available. Here, an overview of
      this (r)evolution is given with emphasis on the differential display method,
      which for many years has been the preferred technique of scientists in diverse
      fields of research. Differential display has also been the method of choice for
      the identification of genes involved in the symbiotic interaction between
      Azorhizobium caulinodans and Sesbania rostrata. The advantages with respect to
      tissue specificity of this particular model system for legume nodulation and the
      results of a screening for early nodulation-related genes have been considered in
      the context of transcriptome analyses in other rhizobium-legume interactions.

PMID- 11522816
TI  - Kinetics and regulation of site-specific endonucleolytic cleavage of human IGF-II
      mRNAs.
AB  - Human insulin-like growth factor II (IGF-II) mRNA can be cleaved at a specific
      site in its 4 kb long 3'-UTR. This yields a stable 3' cleavage product of 1.8 kb
      consisting of a 3'-UTR and a poly(A) tail and an unstable 5' cleavage product
      containing the IGF-II coding region. After cleavage, the 5' cleavage product is
      targeted to rapid degradation and consequently is no longer involved in IGF-II
      protein synthesis. Cleavage is therefore thought to provide an additional way to
      control IGF-II gene expression. In this paper the kinetics and the efficiency of
      cleavage of IGF-II mRNAs are examined. The cleavage efficiency of IGF-II mRNAs
      carrying four different leaders (L1-L4) is enhanced in the highly structured
      leaders L1 and L3. Additionally, under standard cell culture conditions cleavage
      is a slow process that only plays a limited role in destabilisation and
      translation of the IGF-II mRNAs. However, in human Hep3B cells and CaCo2 cells
      which express IGF-II endogenously, cleavage is upregulated 3-5-fold at high cell
      densities. Regulated endonucleolytic cleavage of IGF-II mRNAs is restricted to
      cells in which IGF-II expression is related to specific cell processes.

PMID- 11522815
TI  - Ski interacts with the evolutionarily conserved SNW domain of Skip.
AB  - Ski interacting protein (Skip) has been found to bind to the highly conserved
      region of Ski, which is required for its transforming activity. Ski is a unique
      oncoprotein that is involved in inducing both transformation and differentiation.
      At the molecular level, Ski has been shown to exhibit either co-activator or co
      repressor activity depending on the cellular and promoter context. We were
      interested in further elucidating the biological implications of the Ski-Skip
      interaction. Here we have identified the SNW domain of Skip as the interaction
      region for Ski. This domain of Skip is highly conserved in all the Skip
      homologues identified from different species. Using a series of reporter
      plasmids, we show that Skip is a potent transcriptional activator of many
      different promoters, the activity of which was also mapped to the conserved core
      SNW domain of the protein. Addition of excess Ski further augmented the
      transcriptional activities of Skip, suggesting that one of the ways in which Ski
      brings about transformation is by binding and cooperating with the SNW domain of
      Skip in transcriptional activation.

PMID- 11522817
TI  - The srs2 suppressor of UV sensitivity acts specifically on the RAD5- and MMS2
      dependent branch of the RAD6 pathway.
AB  - The SRS2 gene encodes a helicase that affects recombination, gene conversion and
      DNA damage repair in the yeast Saccharomyces cerevisiae. Loss-of-function
      mutations in srs2 suppress the extreme sensitivity towards UV radiation of rad6
      and rad18 mutants, both of which are impaired in post-replication DNA repair and
      damage-induced mutagenesis. A sub-branch within the RAD6 pathway is mediated by
      RAD5, UBC13 and MMS2, and a comprehensive analysis of the srs2 effect on other
      known members of the RAD6 pathway reported here now demonstrates that suppression
      by srs2 is specific for mutants within this RAD5-dependent sub-system. Further
      evidence for the concerted action of RAD5 with UBC13 and MMS2 in DNA damage
      repair is given by examination of the effects of cell cycle stage as well as
      deletion of other repair systems on the activity of post-replication repair.
      Finally, it is shown that MMS2, like UBC13 and many other repair genes, is
      transcriptionally up-regulated in response to DNA damage. The data presented here
      support the notion that RAD5, UBC13 and MMS2 encode an ensemble of genetically
      and physically interacting repair factors within the RAD6 pathway that is
      coordinately affected by SRS2.

PMID- 11522819
TI  - Enzymatic properties of de novo-type mouse DNA (cytosine-5) methyltransferases.
AB  - We have purified GST-fused recombinant mouse Dnmt3a and three isoforms of mouse
      Dnmt3b to near homogeneity. Dnmt3b3, an isoform of Dnmt3b, did not have DNA
      methylation activity. Dnmt3a, Dnmt3b1 or Dnmt3b2 showed similar activity toward
      poly(dG-dC)-poly(dG-dC) for measuring de novo methylation activity, and toward
      poly(dI-dC)-poly(dI-dC) for measuring total activity. This indicates that the
      enzymes are de novo-type DNA methyltransferases. The enzyme activity was
      inhibited by NaCl or KCl at concentrations >100 mM. The kinetic parameter,
      K(m)(AdoMet), for Dnmt3a, Dnmt3b1 and Dnmt3b2 was 0.4, 1.2 and 0.9 microM when
      poly(dI-dC)-poly(dI-dC) was used, and 0.3, 1.2 and 0.8 microM when poly(dG-dC)
      poly(dG-dC) was used, respectively. The K(m)(DNA) values for Dnmt3a, Dnmt3b1 and
      Dnmt3b2 were 2.7, 1.3 and 1.5 microM when poly(dI-dC)-poly(dI-dC) was used, and
      3.5, 1.0 and 0.9 microM when poly(dG-dC)-poly(dG-dC) was used, respectively. For
      the methylation specificity, Dnmt3a significantly methylated CpG >> CpA. On the
      other hand, Dnmt3b1 methylated CpG > CpT >/= CpA. Immuno-purified Dnmt3a, Myc
      tagged and overexpressed in HEK 293T cells, methylated CpG >> CpA > CpT. Neither
      Dnmt3a nor Dnmt3b1 methylated the first cytosine of CpC.

PMID- 11522818
TI  - An enhancer element 6 kb upstream of the mouse HNF4alpha1 promoter is activated
      by glucocorticoids and liver-enriched transcription factors.
AB  - We have characterized a 700 bp enhancer element around -6 kb relative to the
      HNF4alpha1 transcription start. This element increases activity and confers
      glucocorticoid induction to a heterologous as well as the homologous promoters in
      differentiated hepatoma cells and is transactivated by HNF4alpha1, HNF4alpha7,
      HNF1alpha and HNF1beta in dedifferentiated hepatoma cells. A 240 bp sub-region
      conserves basal and hormone-induced enhancer activity. It contains HNF1, HNF4,
      HNF3 and C/EBP binding sites as shown by DNase I footprinting and electrophoretic
      mobility shift assays using nuclear extracts and/or recombinant HNF1alpha and
      HNF4alpha1. Mutation analyses showed that the HNF1 site is essential for
      HNF1alpha transactivation and is required for full basal enhancer activity, as is
      the C/EBP site. Glucocorticoid response element consensus sites which overlap the
      C/EBP, HNF4 and HNF3 sites are crucial for optimal hormonal induction. We present
      a model that accounts for weak expression of HNF4alpha1 in the embryonic liver
      and strong expression in the newborn/adult liver via the binding sites identified
      in the enhancer.

PMID- 11522820
TI  - A relationship between gene expression and protein interactions on the proteome
      scale: analysis of the bacteriophage T7 and the yeast Saccharomyces cerevisiae.
AB  - The relationship between the similarity of expression patterns for a pair of
      genes and interaction of the proteins they encode is demonstrated both for the
      simple genome of the bacteriophage T7 and the considerably more complex genome of
      the yeast Saccharomyces cerevisiae. Statistical analysis of large-scale gene
      expression and protein interaction data shows that protein pairs encoded by co
      expressed genes interact with each other more frequently than with random
      proteins. Furthermore, the mean similarity of expression profiles is
      significantly higher for respective interacting protein pairs than for random
      ones. Such coupled analysis of gene expression and protein interaction data may
      allow evaluation of the results of large-scale gene expression and protein
      interaction screens as demonstrated for several publicly available datasets. The
      role of this link between expression and interaction in the evolution from
      monomeric to oligomeric protein structures is also discussed.

PMID- 11522821
TI  - Epstein-Barr nuclear antigen 1 binds and destabilizes nucleosomes at the viral
      origin of latent DNA replication.
AB  - The EBNA1 protein of Epstein-Barr virus (EBV) activates latent-phase DNA
      replication by an unknown mechanism that involves binding to four recognition
      sites in the dyad symmetry (DS) element of the viral latent origin of DNA
      replication. Since EBV episomes are assembled into nucleosomes, we have examined
      the ability of Epstein-Barr virus nuclear antigen 1 (EBNA1) to interact with the
      DS element when it is assembled into a nucleosome core particle. EBNA1 bound to
      its recognition sites within this nucleosome, forming a ternary complex, and
      displaced the histone octamer upon competitor DNA challenge. The DNA binding and
      dimerization region of EBNA1 was sufficient for nucleosome binding and
      destabilization. Although EBNA1 was able to bind to nucleosomes containing two
      recognition sites from the DS element positioned at the edge of the nucleosome,
      nucleosome destabilization was only observed when all four sites of the DS
      element were present. Our results indicate that the presence of a nucleosome at
      the viral origin will not prevent EBNA1 binding to its recognition sites. In
      addition, since four EBNA1 recognition sites are required for both nucleosome
      destabilization and efficient origin activation, our findings also suggest that
      nucleosome destabilization by EBNA1 is important for origin activation.

PMID- 11522822
TI  - Inverted repeats as genetic elements for promoting DNA inverted duplication:
      implications in gene amplification.
AB  - Inverted repeats are important genetic elements for genome instability. In the
      current study we have investigated the role of inverted repeats in a DNA
      rearrangement reaction using a linear DNA substrate. We show that linear DNA
      substrates with terminal inverted repeats can efficiently transform Escherichia
      coli. The transformation products contain circular inverted dimers in which the
      DNA sequences between terminal inverted repeats are duplicated. In contrast to
      the recombination/rearrangement product of circular DNA substrates, which is
      exclusively one particular form of the inverted dimer, the rearrangement products
      of the linear DNA substrate consist of two isomeric forms of the inverted dimer.
      Escherichia coli mutants defective in RecBCD exhibit much reduced transformation
      efficiency, suggesting a role for RecBCD in the protection rather than
      destruction of these linear DNA substrates. These results suggest a model in
      which inverted repeats near the ends of a double-strand break can be processed by
      a helicase/exonuclease to form hairpin caps. Processing of hairpin capped DNA
      intermediates can then yield inverted duplications. Linear DNA substrates
      containing terminal inverted repeats can also be converted into inverted dimers
      in COS cells, suggesting conservation of this type of genome instability from
      bacteria to mammalian cells.

PMID- 11522823
TI  - Transcription activation by targeted recruitment of the RNA polymerase II CTD
      phosphatase FCP1.
AB  - Human FCP1 in association with RNAP II reconstitutes a highly specific CTD
      phosphatase activity and is required for recycling RNA polymerase II (RNAP II) in
      vitro. Here we demonstrate that targeted recruitment of FCP1 to promoter
      templates, through fusion to a DNA-binding domain, stimulates transcription. We
      demonstrate that a short region at the C-terminus of the FCP1 protein is required
      and sufficient for activation, indicating that neither the N-terminal phosphatase
      domain nor the BRCT domains are required for transcription activity of DNA-bound
      FCP1. In addition, we demonstrate that the C-terminus region of FCP1 suffices for
      efficient binding in vivo to the RAP74 subunit of TFIIF and is also required for
      the exclusive nuclear localization of the protein. These findings suggest a role
      for FCP1 as a positive regulator of RNAP II transcription.

PMID- 11522824
TI  - The highly conserved DNA-binding domains of A-, B- and c-Myb differ with respect
      to DNA-binding, phosphorylation and redox properties.
AB  - In the Myb family, as in other families of transcription factors sharing similar
      DNA-binding domains (DBDs), diversity of function is believed to rely mainly on
      the less conserved parts of the proteins and on their distinct patterns of
      expression. However, small conserved differences between DBDs of individual
      members could play a role in fine-tuning their function. We have compared the
      highly conserved DBDs of the three vertebrate Myb proteins (A-, B- and c-Myb) and
      found distinct functional differences. While A- and c-Myb behaved virtually
      identically in a variety of DNA-binding assays, B-Myb formed complexes of
      comparatively lower stability, rapidly dissociating under competitive conditions
      and showing less tolerance to binding site variations. The three protein domains
      also differed as substrates for protein kinases. Whereas PKA in theory should
      target the DBDs of A- and c-Myb, but not B-Myb, only c-Myb was phosphorylated by
      PKA. CK2 phosphorylated all three proteins, although on different sites in the N
      terminal region. Finally, B-Myb was remarkably sensitive to cysteine-directed
      oxidation compared to the other Myb proteins. Our data suggest that the small
      differences that have evolved between individual Myb family members lead to clear
      differences in DBD properties even if their sequence recognition remains the
      same.

PMID- 11522825
TI  - 5'- and 3'-terminal nucleotides in the FGFR2 ISAR splicing element core have
      overlapping roles in exon IIIb activation and exon IIIc repression.
AB  - The cell type-specific, mutually-exclusive alternative splicing of the fibroblast
      growth factor receptor 2 (FGFR2) pre-mRNA is tightly regulated. A sequence termed
      ISAR (intronic splicing activator and repressor) has been implicated as an
      important cis regulatory element in both activation of exon IIIb and repression
      of exon IIIc splicing in epithelial cells. In order to better understand how this
      single sequence could have dual roles, we transfected minigenes containing a
      series of 2-bp mutations in the 18 3'-most nucleotides of ISAR that we refer to
      as the ISAR core. Transfection of cells with dual-exon (IIIb and IIIc) minigenes
      revealed that mutation of terminal sequences of the core led to decreased exon
      IIIb inclusion and increased exon IIIc inclusion. Transfection of cells with
      single-exon IIIb minigenes and single-exon IIIc minigenes revealed that mutation
      of terminal sequences of the ISAR core led to decreased exon IIIb inclusion and
      increased exon IIIc inclusion, respectively. Nucleotides of the ISAR core
      responsible for exon IIIb activation appear to overlap very closely with those
      required for exon IIIc repression. We describe a model in which ISAR and a 5'
      intronic sequence known as IAS2 form a stem structure required for simultaneous
      exon IIIb activation and exon IIIc repression.

PMID- 11522826
TI  - DNA-binding activity and subunit interaction of the mariner transposase.
AB  - Mos1 is a member of the mariner/Tc1 family of transposable elements originally
      identified in Drosophila mauritiana. It has 28 bp terminal inverted repeats and
      like other elements of this type it transposes by a cut and paste mechanism,
      inserts at TA dinucleotides and codes for a transposase. This is the only protein
      required for transposition in vitro. We have investigated the DNA binding
      properties of Mos1 transposase and the role of transposase-transposase
      interactions in transposition. Purified transposase recognises the terminal
      inverted repeats of Mos1 due to a DNA-binding domain in the N-terminal 120 amino
      acids. This requires a putative helix-turn-helix motif between residues 88 and
      108. Binding is preferentially to the right hand end, which differs at four
      positions from the repeat at the left end. Cleavage of Mos1 by transposase is
      also preferentially at the right hand end. Wild-type transposase monomers
      interact with each other in a yeast two-hybrid assay and we have used this to
      isolate mutations resulting in reduced interaction. These mutations lie along the
      length of the protein, indicating that transposase-transposase interactions are
      not due to a single interaction domain. One such mutation which retains both DNA
      binding and catalytic activity has greatly reduced ability to excise Mos1 from
      plasmid DNA through coordinate cleavage of the two ends and transposition in
      vitro is lowered to a level 20-fold below that of the wild-type. This suggests
      that transposase-transposase interaction is required to form a synaptic complex
      necessary for coordinate cleavage at the ends of Mos1 during transposition. This
      mutant enzyme allows insertion at dinucleotides other than TA, including
      sequences with GC base pairs. This is the first example of a mariner/Tc1
      transposase with altered target specificity.

PMID- 11522827
TI  - Completion of RNA synthesis by viral RNA replicases.
AB  - How the 5'-terminus of the template affects RNA synthesis by viral RNA replicases
      is poorly understood. Using short DNA, RNA and RNA-DNA chimeric templates that
      can direct synthesis of replicase products, we found that DNA templates tend to
      direct the synthesis of RNA products that are shorter by 1 nt in comparison to
      RNA templates. Template-length RNA synthesis was also affected by the
      concentration of nucleoside triphosphates, the identity of the bases at specific
      positions close to the 5'-terminus and the C2'-hydroxyl of a ribose at the third
      nucleotide from the 5'-terminal nucleotide. Similar requirements are observed
      with two bromoviral replicases, but not with a recombinant RNA-dependent RNA
      polymerase. These results begin to define the interactions needed for the viral
      replicase to complete synthesis of viral RNA.

PMID- 11522828
TI  - Prediction of rho-independent transcriptional terminators in Escherichia coli.
AB  - A new algorithm called RNAMotif containing RNA structure and sequence constraints
      and a thermodynamic scoring system was used to search for intrinsic rho
      independent terminators in the Escherichia coli K-12 genome. We identified all
      135 reported terminators and 940 putative terminator sequences beginning no more
      than 60 nt away from the 3'-end of the annotated transcription units (TU).
      Putative and reported terminators with the scores above our chosen threshold were
      found for 37 of the 53 non-coding RNA TU and for almost 50% of the 2592 annotated
      protein-encoding TU, which correlates well with the number of TU expected to
      contain rho-independent terminators. We also identified 439 terminators that
      could function in a bi-directional fashion, servicing one gene on the positive
      strand and a different gene on the negative strand. Approximately 700 additional
      termination signals in non-coding regions (NCR) far away from the nearest
      annotated gene were predicted. This number correlates well with the excess number
      of predicted 'orphan' promoters in the NCR, and these promoters and terminators
      may be associated with as yet unidentified TU. The significant number of high
      scoring hits that occurred within the reading frame of annotated genes suggests
      that either an additional component of rho-independent terminators exists or that
      a suppressive mechanism to prevent unwanted termination remains to be discovered.

PMID- 11522829
TI  - Association of galectin-1 and galectin-3 with Gemin4 in complexes containing the
      SMN protein.
AB  - In previous studies we showed that galectin-1 and galectin-3 are factors required
      for the splicing of pre-mRNA, as assayed in a cell-free system. Using a yeast two
      hybrid screen with galectin-1 as bait, Gemin4 was identified as a putative
      interacting protein. Gemin4 is one component of a macromolecular complex
      containing approximately 15 polypeptides, including SMN (survival of motor
      neuron) protein. Rabbit anti-galectin-1 co-immunoprecipitated from HeLa cell
      nuclear extracts, along with galectin-1, polypeptides identified to be in this
      complex: SMN, Gemin2 and the Sm polypeptides of snRNPs. Direct interaction
      between Gemin4 and galectin-1 was demonstrated in glutathione S-transferase (GST)
      pull-down assays. We also found that galectin-3 interacted with Gemin4 and that
      it constituted one component of the complex co-immunoprecipitated with galectin
      1. Indeed, fragments of either Gemin4 or galectin-3 exhibited a dominant negative
      effect when added to a cell-free splicing assay. For example, a dose-dependent
      inhibition of splicing was observed in the presence of exogenously added N
      terminal domain of galectin-3 polypeptide. In contrast, parallel addition of
      either the intact galectin-3 polypeptide or the C-terminal domain failed to yield
      the same effect. Using native gel electrophoresis to detect complexes formed by
      the splicing extract, we found that with addition of the N-terminal domain the
      predominant portion of the radiolabeled pre-mRNA was arrested at a position
      corresponding to the H-complex. Inasmuch as SMN-containing complexes have been
      implicated in the delivery of snRNPs to the H-complex, these results provide
      strong evidence that galectin-1 and galectin-3, by interacting with Gemin4, play
      a role in spliceosome assembly in vivo.

PMID- 11522830
TI  - Reversal of methylation-mediated repression with short-chain fatty acids:
      evidence for an additional mechanism to histone deacetylation.
AB  - We have constructed a stable cell line, human embryonal kidney 293M+, containing
      a lacZ reporter gene controlled by an in vitro methylated hormone-responsive
      enhancer. Methylation of the enhancer-promoter abolishes lacZ expression
      controlled by ponasterone A (an analogue of ecdysone). Ponasterone A-induced
      expression is restored by the short-chain fatty acids valeric > butyric >
      propionic > acetic acid, but not by the histone deacetylase inhibitors
      trichostatin A and suberoylanilide hydroxamic acid (SAHA). lacZ expression is
      restored to levels approaching that from an unmethylated counterpart. Incubation
      with short-chain fatty acids alone does not promote demethylation of the lacZ
      promoter, however, some demethylation (30%) is observed when transcription is
      triggered by addition of ponasterone A. Similar levels of hyperacetylated
      histones H3 and H4 were observed in cells treated with short-chain fatty acids,
      trichostatin A or SAHA. In vivo DNase I footprinting indicates a more open
      chromatin structure at the promoter region for butyric acid-treated cells. A
      synergistic effect in reversing the methylation-mediated repression of the lacZ
      gene is obtained by combined treatments with the normally ineffective compounds
      trichostatin A and the short-chain fatty acid caproic acid. Our results suggest
      the existence of an alternative silencing mechanism to histone deacetylation in
      executing methylation-directed gene silencing.

PMID- 11522831
TI  - 5'-bis-pyrenylated oligonucleotides displaying excimer fluorescence provide
      sensitive probes of RNA sequence and structure.
AB  - Oligonucleotide conjugates bearing two pyrene residues attached to 5'-phosphate
      through a phosphoramide bond were synthesised. Fluorescence spectra of the
      conjugates show a peak typical of monomer emission (lambda(max) 382 nm) and a
      broad emission peak with lambda(max )476 nm, which indicates the excimer
      formation between the two pyrene residues. Conjugation of these two pyrene
      residues to the 5'-phosphate of oligonucleotides does not affect the stabilities
      of heteroduplexes formed by conjugates with the corresponding linear strands. A
      monomer fluorescence of the conjugates is considerably affected by the
      heteroduplex formation allowing the conjugates to be used as fluorescent
      hybridisation probes. The 5'-bis-pyrenylated oligonucleotides have been
      successfully used for investigation of affinity and kinetics of antisense
      oligonucleotides binding to the multidrug resistance gene 1 (PGY1/MDR1) mRNA. The
      changes of excimer fluorescence of the conjugates occurring during hybridisation
      depended on the structure of the binding sites: hybridisation to heavily
      structured parts of RNA resulted in quenching of the excimer fluorescence, while
      binding to RNA regions with a loose secondary structure was accompanied by an
      enhancement of the excimer fluorescence. Potentially, these conjugates may be
      considered as fluorescent probes for RNA structure investigation.

PMID- 11522832
TI  - ERB1, the yeast homolog of mammalian Bop1, is an essential gene required for
      maturation of the 25S and 5.8S ribosomal RNAs.
AB  - We have recently shown that the mammalian nucleolar protein Bop1 is involved in
      synthesis of the 28S and 5.8S ribosomal RNAs (rRNAs) and large ribosome subunits
      in mouse cells. Here we have investigated the functions of the Saccharomyces
      cerevisiae homolog of Bop1, Erb1p, encoded by the previously uncharacterized open
      reading frame YMR049C. Gene disruption showed that ERB1 is essential for
      viability. Depletion of Erb1p resulted in a loss of 25S and 5.8S rRNAs synthesis,
      while causing only a moderate reduction and not a complete block in 18S rRNA
      formation. Processing analysis showed that Erb1p is required for synthesis of 7S
      pre-rRNA and mature 25S rRNA from 27SB pre-rRNA. In Erb1p-depleted cells these
      products of 27SB processing are largely absent and 27SB pre-rRNA is under
      accumulated, apparently due to degradation. In addition, depletion of Erb1p
      caused delayed processing of the 35S pre-rRNA. These findings demonstrate that
      Erb1p, like its mammalian counterpart Bop1, is required for formation of rRNA
      components of the large ribosome particles. The similarities in processing
      defects caused by functional disruption of Erb1p and Bop1 suggest that late steps
      in maturation of the large ribosome subunit rRNAs employ mechanisms that are
      evolutionarily conserved throughout eukaryotes.

PMID- 11522834
TI  - Incorporation of a cationic aminopropyl chain in DNA hairpins: thermodynamics and
      hydration.
AB  - We report on the physicochemical effects resulting from incorporating a 5-(3
      aminopropyl) side chain onto a 2'-deoxyuridine (dU) residue in a short DNA
      hairpin. A combination of spectroscopy, calorimetry, density and ultrasound
      techniques were used to investigate both the helix-coil transition of a set of
      hairpins with the following sequence: d(GCGACTTTTTGNCGC) [N = dU, deoxythymidine
      (dT) or 5-(3-aminopropyl)-2'-deoxyuridine (dU*)], and the interaction of each
      hairpin with Mg(2+). All three molecules undergo two-state transitions with
      melting temperatures (T(M)) independent of strand concentration that indicates
      their intramolecular hairpin formation. The unfolding of each hairpin takes place
      with similar T(M) values of 64-66 degrees C and similar thermodynamic profiles.
      The unfavorable unfolding free energies of 6.4-6.9 kcal/mol result from the
      typical compensation of unfavorable enthalpies, 36-39 kcal/mol, and favorable
      entropies of approximately 110 cal/mol. Furthermore, the stability of each
      hairpin increases as the salt concentration increases, the T(M)-dependence on
      salt yielded slopes of 2.3-2.9 degrees C, which correspond to counterion releases
      of 0.53 (dU and dT) and 0.44 (dU*) moles of Na(+) per mole of hairpin. Absolute
      volumetric and compressibility measurements reveal that all three hairpins have
      similar hydration levels. The electrostatic interaction of Mg(2+) with each
      hairpin yielded binding affinities in the order: dU > dT > dU*, and a similar
      release of 2-4 electrostricted water molecules. The main result is that the
      incorporation of the cationic 3-aminopropyl side chain in the major groove of the
      hairpin stem neutralizes some local negative charges yielding a hairpin molecule
      with lower charge density.

PMID- 11522833
TI  - Rpm2p: separate domains promote tRNA and Rpm1r maturation in Saccharomyces
      cerevisiae mitochondria.
AB  - Rpm2p is a protein subunit of yeast mitochondrial RNase P and is also required
      for the maturation of Rpm1r, the mitochondrially-encoded RNA subunit of the
      enzyme. Previous work demonstrated that an insertional disruption of RPM2, which
      produces the C-terminally truncated protein Rpm2-DeltaCp, supports growth on
      glucose but cells lose some or all of their mitochondrial genome and become
      petite. These petites, even if they retain the RPM1 locus, lose their ability to
      process the 5'-ends of mitochondrial tRNA. We report here that if strains
      containing the truncated RPM2 allele are created and maintained on respiratory
      carbon sources they have wild-type mitochondrial genomes, and a significant
      portion of tRNA transcripts are processed. In contrast, precursor Rpm1r
      transcripts accumulate and mature Rpm1r is not made. These data show that one
      function of the deleted C-terminal region is in the maturation of Rpm1r, and that
      this region and mature Rpm1r are not absolutely required for RNase P activity.
      Finally, we demonstrate that full activity can be restored if the N-terminal and
      C-terminal domains of Rpm2p are supplied in trans.

PMID- 11522835
TI  - Five-base codons for incorporation of nonnatural amino acids into proteins.
AB  - Extension of the genetic code for the introduction of nonnatural amino acids into
      proteins was examined by using five-base codon-anticodon pairs. A streptavidin
      mRNA containing a CGGUA codon at the Tyr54 position and a tRNA(UACCG) chemically
      aminoacylated with a nonnatural amino acid were added to an Escherichia coli in
      vitro translation system. Western blot analysis indicated that the CGGUA codon is
      decoded by the aminoacyl-tRNA containing the UACCG anticodon. HPLC analysis of
      the tryptic fragment of the translation product revealed that the nonnatural
      amino acid was incorporated corresponding to the CGGUA codon without affecting
      the reading frame adjacent to the CGGUA codon. Another 15 five-base codons
      CGGN(1)N(2), where N(1) and N(2) indicate one of four nucleotides, were also
      successfully decoded by aminoacyl-tRNAs containing the complementary five-base
      anticodons. These results provide a novel strategy for nonnatural mutagenesis as
      well as a novel insight into the mechanism of frameshift suppression.

PMID- 11522836
TI  - Characterization of a multi-functional metal-mediated nuclease by MALDI-TOF mass
      spectrometry.
AB  - Mass spectrometric analysis of reaction products allows simultaneous
      characterization of activities mediated by multifunctional enzymes. By use of
      MALDI-TOF mass spectrometry, the relative influence of magnesium and manganese
      promoted exonuclease and phosphatase activities of Esherichia coli exonuclease
      III have been quantitatively measured, offering a rapid and sensitive alternative
      to radioactivity quantification and gel electrophoresis procedures for
      determination of reaction rate constants. Manganese is found to promote higher
      levels of exonuclease activity, which could be a source of mutagenic effects if
      this ion were selected as the natural cofactor. Several potential applications of
      these methods to quantitative studies of DNA repair chemistry are also described.

PMID- 11522837
TI  - Mechanism of mammalian mitochondrial DNA replication: import of mitochondrial
      transcription factor A into isolated mitochondria stimulates 7S DNA synthesis.
AB  - The light strand promoter of mammalian mitochondrial DNA gives rise to a primary
      transcript, but also to the RNA primer necessary for initiation of replication
      and 7S DNA synthesis as well as 7S RNA. Here we have studied the turnover of 7S
      DNA in isolated rat liver mitochondria and whether import of mitochondrial
      transcription factor A (mtTFA), which is necessary for transcription initiation,
      increases its rate of synthesis. 7S DNA was present as two species, probably due
      to two different sites of RNA-DNA transition. Time course and pulse-chase
      experiments showed that the half-life of this DNA is approximately 45 min. Import
      of mtTFA, produced in vitro, into the mitochondrial matrix in stoichiometric
      amounts significantly increased the rate of 7S DNA formation. We conclude that
      isolated rat liver mitochondria faithfully synthesize and degrade 7S DNA and that
      increased matrix levels of mtTFA are sufficient to increase its rate of
      synthesis, strongly supporting the hypothesis that this process is transcription
      primed.

PMID- 11522839
TI  - Synthesis and monitored selection of nucleotide surrogates for binding T:A base
      pairs in homopurine-homopyrimidine DNA triple helices.
AB  - A total of 16 oligodeoxyribonucleotides of general sequence 5'-TCTTCTZTCTTTCT-3',
      where Z denotes an N-acyl-N-(2-hydroxyethyl)glycine residue, were prepared via
      solid phase synthesis. The ability of these oligonucleotides to form triplexes
      with the duplex 5'-AGAAGATAGAAAGA-HEG-TCTTTCTATCTTCT-3', where HEG is a
      hexaethylene glycol linker, was tested. In these triplexes, an 'interrupting' T:A
      base pair faces the Z residue in the third strand. Among the acyl moieties of Z
      tested, an anthraquinone carboxylic acid residue linked via a glycinyl group gave
      the most stable triplex, whose UV melting point was 8.4 degrees C higher than
      that of the triplex with 5'-TCTTCTGTCTTTCT-3' as the third strand. The results
      from exploratory nuclease selection experiments suggest that a combinatorial
      search for strands capable of recognizing mixed sequences by triple helix
      formation is feasible.

PMID- 11522838
TI  - Determination of optimal sites of antisense oligonucleotide cleavage within
      TNFalpha mRNA.
AB  - Antisense oligonucleotides provide a powerful tool in order to determine the
      consequences of the reduced expression of a selected target gene and may include
      target validation and therapeutic applications. Methods of predicting optimum
      antisense sites are not always effective. We have compared the efficacy of
      antisense oligonucleotides, which were selected in vitro using random
      combinatorial oligonucleotide libraries of differing length and complexity, upon
      putative target sites within TNFalpha mRNA. The relationship of specific target
      site accessibility and oligonucleotide efficacy with respect to these parameters
      proved to be complex. Modification of the length of the recognition sequence of
      the oligonucleotide library illustrated that independent target sites
      demonstrated a preference for antisense oligonucleotides of a defined and
      independent optimal length. The efficacy of antisense oligonucleotide sequences
      selected in vitro paralleled that observed in phorbol 12-myristate 13-acetate
      (PMA)-activated U937 cells. The application of methylphosphonate:phosphodiester
      chimaeric oligonucleotides to U937 cells reduced mRNA levels to up to 19.8% that
      of the untreated cell population. This approach provides a predictive means to
      profile any mRNA of known sequence with respect to the identification and
      optimisation of sites accessible to antisense oligonucleotide activity.

PMID- 11522840
TI  - Detection of in vivo protein interactions between Snf1-related kinase subunits
      with intron-tagged epitope-labelling in plants cells.
AB  - Plant orthologs of the yeast sucrose non-fermenting (Snf1) kinase and mammalian
      AMP-activated protein kinase (AMPK) represent an emerging class of important
      regulators of metabolic and stress signalling. The catalytic alpha-subunits of
      plant Snf1-related kinases (SnRKs) interact in the yeast two-hybrid system with
      different proteins that share conserved domains with the beta- and gamma-subunits
      of Snf1 and AMPKs. However, due to the lack of a robust technique allowing the
      detection of protein interactions in plant cells, it is unknown whether these
      proteins indeed occur in SnRK complexes in vivo. Here we describe a double
      labelling technique, using intron-tagged hemagglutinin (HA) and c-Myc epitope
      sequences, which provides a simple tool for co-immunopurification of interacting
      proteins expressed in Agrobacterium-transformed Arabidopsis cells. This generally
      applicable plant protein interaction assay was used to demonstrate that
      AKINbeta2, a plant ortholog of conserved Snf1/AMPK beta-subunits, forms different
      complexes with the catalytic alpha-subunits of Arabidopsis SnRK protein kinases
      AKIN10 and AKIN11 in vivo.

PMID- 11522842
TI  - Quantitative target display: a method to screen yeast mutants conferring
      quantitative phenotypes by 'mutant DNA fingerprints'.
AB  - Whole genome sequencing of several microbes has revealed thousands of genes of
      unknown function. A large proportion of these genes seem to confer subtle
      quantitative phenotypes or phenotypes that do not have a plate screen. We report
      a novel method to monitor such phenotypes, where the fitness of mutants is
      assessed in mixed cultures under competitive growth conditions, and the abundance
      of any individual mutant in the pool is followed by means of its unique feature,
      namely the mutation itself. A mixed population of yeast mutants, obtained through
      transposon mutagenesis, was subjected to selection. The DNA regions (targets)
      flanking the transposon, until nearby restriction sites, are then quantitatively
      amplified by means of a ligation-mediated PCR method, using transposon-specific
      and adapter-specific primers. The amplified PCR products correspond to mutated
      regions of the genome and serve as 'mutant DNA fingerprints' that can be
      displayed on a sequencing gel. The relative intensity of the amplified DNA
      fragments before and after selection match with the relative abundance of
      corresponding mutants, thereby revealing the fate of the mutants during
      selection. Using this method we demonstrate that UBI4, YDJ1 and HSP26 are
      essential for stress tolerance of yeast during ethanol production. We anticipate
      that this method will be useful for functional analysis of genes of any microbe
      amenable to insertional mutagenesis.

PMID- 11522841
TI  - Development of an effective gene delivery system: a study of complexes composed
      of a peptide-based amphiphilic DNA compaction agent and phospholipid.
AB  - We recently described a basic technology to efficiently combine compacted DNA
      with phospholipids and hydrophobic peptides, to produce homogenous complexes that
      are completely resistant to nuclease. We have developed this technology further
      to form gene delivery complexes that transfect cells effectively in vitro. In
      addition to plasmid DNA, the complexes contained two basic components: (i) a DNA
      compacting peptide (-CGKKKFKLKH), either conjugated to lipid or extended to
      contain (WLPLPWGW-) and (ii) either phosphatidylethanolamine or
      phosphatidylcholine. Complexes containing a 5.5-fold charge equivalence (peptide
      charge/DNA charge) of WLPLPWGWCGKKKFKLKH and 5 nmol
      dimyristoleoylphosphatidylethanolamine/microg DNA produced the highest luciferase
      gene expression, exceeding 1 x 10(9) relative light units/s/mg protein (>3 microg
      luciferase per mg protein). These complexes transfected OVCAR-3, COS-7 and HeLa
      cells at either similar or superior levels when compared to polyethylenimine or
      lipofectamine complexes. With green fluorescent protein reporter gene, >50% of
      HeLa cells were positive 30 h after addition of these complexes. Furthermore,
      these optimal complexes were the least sensitive to pre-treatment of cells with
      chloroquine, indicating efficient endosomal escape. Our results indicated that
      self-assembling complexes of plasmid DNA, amphiphilic peptide and
      phosphatidylethanolamine are highly effective non-viral gene delivery systems.

PMID- 11522843
TI  - A novel method to isolate the common fraction of two DNA samples: hybrid specific
      amplification (HSA).
AB  - Hybrid specific amplification (HSA) is a novel simple method elaborated in order
      to isolate the common fraction of two DNA samples while avoiding the background
      due to repeated sequences. The method is based on the suppressive PCR principle,
      associated with a Cot1 pre-hybridization step. In recent work we demonstrated
      that hyperprolificity observed in Booroola ewes is associated with a mutation in
      the bone morphogenetic protein receptor IB gene (BMPR-IB). We applied HSA between
      ovarian cDNA and DNA from four BAC clones containing BMPR-IB in order to test for
      the presence of other genes expressed in ovary and to isolate additional BMPR-IB
      exon sequences. Of the 460 clones obtained, none contained repeated sequences. We
      successfully obtained 37 clones representing the major part of BMPR-IB coding
      sequence, together with 5'- and 3'-UTR sequences. Here we have successfully
      applied HSA to a particular tissue, but it should be possible to trap the common
      fraction of two DNA samples, whatever their nature.

PMID- 11522844
TI  - An efficient procedure for genotyping single nucleotide polymorphisms.
AB  - Analysis of single nucleotide polymorphisms (SNPs) has been and will be
      increasingly utilized in various genetic disciplines, particularly in studying
      genetic determinants of complex diseases. Such studies will be facilitated by
      rapid, simple, low cost and high throughput methodologies for SNP genotyping. One
      such method is reported here, named tetra-primer ARMS-PCR, which employs two
      primer pairs to amplify, respectively, the two different alleles of a SNP in a
      single PCR reaction. A computer program for designing primers was developed.
      Tetra-primer ARMS-PCR was combined with microplate array diagonal gel
      electrophoresis, gaining the advantage of high throughput for gel-based
      resolution of tetra-primer ARMS-PCR products. The technique was applied to
      analyse a number of SNPs and the results were completely consistent with those
      from an independent method, restriction fragment length polymorphism analysis.

PMID- 11522845
TI  - Linear 2' O-Methyl RNA probes for the visualization of RNA in living cells.
AB  - U1snRNA, U3snRNA, 28 S ribosomal RNA, poly(A) RNA and a specific messenger RNA
      were visualized in living cells with microinjected fluorochrome-labeled 2' O
      Methyl oligoribonucleotides (2' OMe RNA). Antisense 2' OMe RNA probes showed fast
      hybridization kinetics, whereas conventional oligodeoxyribonucleotide (DNA)
      probes did not. The nuclear distributions of the signals in living cells were
      similar to those found in fixed cells, indicating specific hybridization.
      Cytoplasmic ribosomal RNA, poly(A) RNA and mRNA could hardly be visualized,
      mainly due to a rapid entrapment of the injected probes in the nucleus. The
      performance of linear probes was compared with that of molecular beacons, which
      due to their structure should theoretically fluoresce only upon hybridization. No
      improvements were achieved however with the molecular beacons used in this study,
      suggesting opening of the beacons by mechanisms other than hybridization. The
      results show that linear 2' OMe RNA probes are well suited for RNA detection in
      living cells, and that these probes can be applied for dynamic studies of highly
      abundant nuclear RNA. Furthermore, it proved feasible to combine RNA detection
      with that of green fluorescent protein-labeled proteins in living cells. This was
      applied to show co-localization of RNA with proteins and should enable RNA
      protein interaction studies.

PMID- 11522847
TI  - Cyclooxygenase-2 and macula densa control of renin secretion.

PMID- 11522846
TI  - Selective 'stencil'-aided pre-PCR cleavage of wild-type sequences as a novel
      approach to detection of mutant K-RAS.
AB  - The enriched PCR widely used for detection of mutant K-RAS in either tumor
      tissues or circulating DNA was modified so that abundant wild-type K-RAS alleles
      are cleaved prior to PCR. We took advantage of an AluI recognition site located
      immediately upstream of the K-RAS codon 12. The site was reconstituted upon DNA
      denaturation followed by annealing with a 'stencil', a 16-bp synthetic
      oligonucleotide complementary to the wild-type sequence. As opposed to normal K
      RAS, the mutant allele forms, upon annealing with the stencil, a mismatch at the
      codon 12 which lies within the AluI enzyme binding site and partially inhibits
      its activity. The mismatch also lowers the melting temperature of the stencil
      mutant K-RAS double helix as compared to stencil-wild-type duplex, so that only
      the latter is double stranded and selectively digested by AluI at elevated
      temperatures. The proposed method of stencil-aided mutation analysis (SAMA) based
      on selective pre-PCR elimination of wild-type sequences can be highly
      advantageous for detection of mutant K-RAS due to: (i) an enhanced sensitivity
      because of reduced competition with a great excess of normal K-RAS, and (ii) a
      decrease in a number of false-positive results from Taq polymerase errors.
      Application of SAMA for generalized detection of DNA mutations is discussed.

PMID- 11522848
TI  - Statins: effects beyond cholesterol lowering.

PMID- 11522849
TI  - ADMA (asymmetric dimethylarginine): an atherosclerotic disease mediating agent in
      patients with renal disease?

PMID- 11522850
TI  - After 15 years of success--perspectives of erythropoietin therapy.

PMID- 11522851
TI  - Kt/V: finding the tree within the woods.

PMID- 11522852
TI  - Mycophenolate mofetil: implications for the treatment of glomerular disease.

PMID- 11522854
TI  - Long-term experience with Thomas shunt.

PMID- 11522853
TI  - Anti-interleukin-2 receptor antibodies: basiliximab and daclizumab.

PMID- 11522855
TI  - Long-term experience with the Thomas Shunt.

PMID- 11522856
TI  - Nuclear factor kappaB for the nephrologist.

PMID- 11522857
TI  - Regulation of endothelin-1 and transforming growth factor-beta1 production in
      cultured proximal tubular cells by albumin and heparan sulphate
      glycosaminoglycans.
AB  - BACKGROUND: Both endothelin-1 (ET-1) and transforming growth factor beta 1 (TGF
      beta1) have been implicated in the progression of interstitial fibrosis. In the
      present study we enquired if albumin influences the production of these factors
      in cultured human proximal tubular epithelial cells (PTEC) and if heparan
      sulphate glycosaminoglycans (HS-GAG) can inhibit this production. METHODS: ET-1
      and TGF-beta1 production in supernatants of PTEC was measured by RIA and ELISA
      respectively. In addition semi-quantitative reverse transcription polymerase
      chain reaction (RT-PCR) was performed to study differences in ET-1 and TGF-beta1
      mRNA expression. To demonstrate ET-1 or TGF-beta1 binding to heparin or HS-GAG,
      binding studies by means of dot blot analysis were carried out. RESULTS: TGF
      beta1 and ET-1 were both produced in different concentrations, depending on the
      PTEC culture tested. Human serum albumin (HSA) up-regulated the production of
      both factors in a time and dose dependent fashion. The production of these
      factors was inhibited by heparin under basal and stimulatory conditions. ET-1
      production was only inhibited by HS-GAG with a high degree of sulphation. For the
      inhibition of TGF-beta1 production, the sulphation of HS-GAG was less critical.
      TGF-beta1, but not ET-1 mRNA expression was inhibited by HS-GAG. Inhibition of
      sulphation of cell surface HS-GAG resulted in the inhibition of ET-1 but not TGF
      beta1 production. Both factors were able to bind to HS-GAG, although this
      required different amounts of HS-GAG sulphation for each factor. CONCLUSIONS: Our
      data demonstrate that in PTEC the release of pro-fibrogenic factors can be
      inhibited by HS-GAG. This may explain to some extent the beneficial effect of
      heparin in the treatment of interstitial fibrosis.

PMID- 11522858
TI  - Cultured rat glomerular epithelial cells show gene expression and production of
      transforming growth factor-beta: expression is enhanced by thrombin.
AB  - BACKGROUND: Glomerular crescents play an important role in progressive glomerular
      injury. The lesions consist of epithelial cells, macrophages, and deposits of
      fibrin and extracellular matrix. Transforming growth factor beta (TGF-beta)
      contributes to the modulation of cell growth and extracellular matrix synthesis.
      Thrombin is involved in fibrin formation in crescents. The purpose of this study
      was to examine whether glomerular epithelial cells (GEC) could produce TGF-beta,
      and if so, to clarify the role of TGF-beta in GEC proliferation. We also
      investigated whether thrombin could modulate the production of TGF-beta and
      extracellular matrix by GEC. METHODS: Bioassay using the TGF-beta-dependent mink
      pulmonary epithelial cell line (CCL-64), immunoblot analysis, and reverse
      transcriptase polymerase chain reaction (RT-PCR) were used to demonstrate TGF
      beta production by rat GEC. TGF-beta gene expression was examined by RT-PCR in
      GEC incubated with thrombin, and type IV collagen and fibronectin were quantified
      by enzyme immunoassay in culture supernatants of GEC incubated with thrombin or
      TGF-beta. RESULTS: TGF-beta activity was demonstrated in GEC supernatants by
      bioassay. Immunoblot analysis of concentrated culture supernatants using anti-TGF
      beta antibody revealed a 12.5-kDa protein, which was compatible with TGF-beta.
      Concentrated GEC supernatants inhibited GEC proliferation as well as porcine TGF
      beta. RT-PCR demonstrated TGF-beta gene expression in GEC. Thrombin (0.5-5.0
      U/ml) enhanced TGF-beta mRNA expression in a dose-dependent manner. Thrombin (5.0
      U/ml) and porcine TGF-beta (5.0 ng/ml) stimulated the production of type IV
      collagen and fibronectin by GEC. CONCLUSIONS: Rat GEC produce TGF-beta in vitro.
      Thrombin may participate in the progression of glomerulosclerosis in crescentic
      glomerulonephritis through the stimulation of TGF-beta production by GEC.

PMID- 11522859
TI  - Th2 predominance at the single-cell level in patients with IgA nephropathy.
AB  - BACKGROUND: Abnormalities of lymphocyte function have been reported to be
      involved in the pathogenesis of IgA nephropathy (IgA-N). The aim of this study
      was to investigate helper T (Th) predominance at the single-cell level, one of
      the abnormalities of lymphocyte function in IgA-N. METHODS: Using flowcytometry,
      we assessed the levels of circulating Th cells in IgA-N patients (n=30), and in
      normal individuals (n=30) based on the expression of intracellular Th1 cytokines
      for interleukin-2 (IL-2) and interferon-gamma (IFN-gamma), and of intracellular
      Th2 cytokines for IL-4, IL-10, and IL-13. Because the production of each cytokine
      had a specific time course, we examined cytokine synthesis at 3, 6, 9, and 12 h
      after stimulation. RESULTS: The percentages of IL-2-positive Th cells from IgA-N
      patients were significantly lower than in normal individuals at 6, 9, and 12 h,
      with the difference becoming greater with time. The number of IFN-gamma-positive
      Th cells in IgA-N patients was significantly lower than in normal individuals at
      9 h, and the number of IFN-gamma-positive Th cells increased more at 12 h than at
      3 h in both groups. IL-4 and IL-13 expression was increased in patients with IgA
      N at 6 h compared with normal individuals. In IgA-N patients, the percentage of
      IL-10-positive Th cells was significantly higher than that in normal individuals
      at each time-point. CONCLUSION: A polarization toward Th2 response at the
      stimulated lymphocyte level may lead to immune abnormalities in IgA-N.

PMID- 11522860
TI  - Clinical features and long-term outcome of obesity-associated focal segmental
      glomerulosclerosis.
AB  - BACKGROUND: Several cases of obesity-associated focal segmental
      glomerulosclerosis (OB-FSG) have been reported but little is known about the
      clinico-pathological features of this entity and its long-term outcomes. METHODS:
      We studied 15 obese patients (BMI 35+/-5.2 kg/m(2)) with biopsy-proven FSG. They
      were compared with a control group of 15 non-obese patients with idiopathic FSG
      (I-FSG). RESULTS: Mean proteinuria at the time of renal biopsy was 3.1+/-2 g/24 h
      in OB-FSG; it reached the nephrotic range (> or =3.5 g/24 h) during follow-up in
      12 patients (80%), but none of them had oedema, hypoproteinaemia, or
      hypoalbuminaemia. Proteinuria was more marked amongst I-FSG (6.5+/-4.2 g/24 h)
      and most of them developed oedema and biochemical nephrotic syndrome.
      Glomerulomegaly was observed in all renal biopsies from OB-FSG patients (mean
      glomerular diameter 256+/-24 microm in OB-FSG vs 199+/-26 microm in I-FSG,
      P<0.001). Twelve OB-FSG patients (80%) were treated with ACE inhibitors (ACEI)
      and proteinuria significantly decreased within the first 6 months of treatment
      but showed a later increase. None of the obese patients achieved a sustained
      weight loss. Seven (46%) patients with OB-FSG experienced a progressive renal
      insufficiency and five of them started intermittent dialysis. Kaplan-Meier
      estimated probabilities of renal survival after 5 and 10 years were 77 and 51%,
      respectively, in OB-FSG patients, and 52 and 30% in I-FSG (P<0.05). The risk of
      developing progressive renal failure among OB-FSG patients was statistically
      correlated with serum creatinine and creatinine clearance at presentation.
      CONCLUSIONS: OB-FSG indicates a poor prognosis with almost one-half of patients
      developing advanced renal failure. Knowledge of the clinico-pathological features
      of this entity (obesity, FSG lesions with glomerulomegaly, absence of nephrotic
      syndrome despite nephrotic-range proteinuria) should be helpful in establishing
      an accurate and early diagnosis.

PMID- 11522861
TI  - Thyroxine treatment induces upregulation of renin-angiotensin-aldosterone system
      due to decreasing effective plasma volume in patients with primary myxoedema.
AB  - BACKGROUND: In experimental animals and humans, hypothyroidism is associated with
      fluid retention and generalized oedema, increased antidiuretic hormone (ADH),
      decreased atrial natriuretic hormone (ANH), and decreased renin-angiotensin
      aldosterone system (RAAS), which subsequently can be corrected by thyroid hormone
      replacement. The purpose of this study was to determine the effect of thyroxine
      therapy on RAAS and neurohormones affecting water and electrolyte metabolism and
      the reason for these changes in patients with primary myxoedema. METHODS: We
      measured changes in the plasma renin activity (PRA), serum aldosterone (Aldo),
      ADH, ANH levels, serum and 24 h urinary electrolytes and osmolalities, and
      cardiac function in 22 female patients with primary myxoedema before and after
      correction of hypothyroidism. We also evaluated age-, sex-, and BMI-matched 15
      healthy control subjects (Cont). RESULTS: It took an average of 4.3 months
      (range, 3-9 months) to normalize thyroid function. The mean reductions of body
      weight and estimated plasma volume were 1.8+/-1.0 kg (P=0.002) and 8.5%
      (P<0.001), respectively. In addition, serum Na+ and osmolality and the
      haematocrit were significantly elevated after correction of hypothyroidism
      (P<0.01 and P<0.001, respectively). Increased F(E)Na and C(OSM) (P<0.05) levels
      in patients with hypothyroidism (Ho) compared with those in Cont did not change
      after thyroxine therapy (Eu). However, C(H(2)O), U(E)K, F(E)K, and TTKG levels as
      well as creatinine clearance (Ccr) were markedly increased in Eu compared with Ho
      and Cont (P<0.01, respectively). Increased plasma ADH concentration and decreased
      plasma ANH concentration were normalized compared to Cont after thyroxine therapy
      (P<0.001 and P<0.01, respectively). Low PRA and serum Aldo concentration in Ho
      were significantly increased in Eu (P<0.001 and P<0.01, respectively). In
      addition, increased left ventricular mass index and decreased cardiac output in
      Ho were normalized compared to Cont after thyroxine therapy (P<0.01,
      respectively) CONCLUSIONS: These findings suggest that the exaggerated
      upregulation of RAAS after correction of hypothyroidism in patients with primary
      myxoedema is associated with an increase in Ccr and a decrease in plasma volume
      resulting from water diuresis, natriuresis, osmotic diuresis and inappropriate
      changes in plasma ADH and ANH levels. The improved renal function coincided with
      an amelioration of cardiac function. These changes seem to be an adaptive
      response for preventing excessive plasma volume and weight loss after thyroxine
      therapy.

PMID- 11522862
TI  - Plasma levels of soluble CD30 are increased in children with chronic renal
      failure and with primary growth deficiency and decrease during treatment with
      recombination human growth hormone.
AB  - BACKGROUND: Previous studies have suggested that in vivo Th2 lymphocyte
      activation is related to increased soluble CD30 (sCD30) plasma levels. As various
      hormones (dehydroepiandrosterone, glucocorticoids, progesterone) can regulate the
      Th1/Th2 balance, and because growth hormone (GH) enhances lymphocyte function, we
      measured sCD30 plasma levels, before and after treatment with recombinant human
      GH (rhGH), in children with growth failure due to chronic renal failure (CRF) or
      to isolated GH deficiency in order to evaluate the potential effects of rhGH
      treatment on Th1/Th2 balance. METHODS: sCD30 plasma levels were determined by
      ELISA assay in 30 children with CRF (mean age 10.7+/-3.7 years), in five children
      with isolated GH deficiency (mean age 11.4+/-2.6 years), and in 10 normal
      controls (mean age 10.1+/-3.5 years). RESULTS: sCD30 levels were higher in the 30
      children with CRF than in the 10 controls (179.8+/-79.4 vs 11.3+/-10.9 U/ml,
      P<0.001) exhibiting an inverse correlation with glomerular filtration rate (GFR)
      (r=-0.7860, P<0.001). In 11 children with CRF, after 19.9+/-16.7 months of rhGH
      treatment, a decrease of sCD30 plasma level (170+/-50 vs 134+/-49 U/ml, P<0.01)
      was observed. The five children with primary GH deficiency had higher sCD30
      plasma level than controls (mean 147+/-105 vs 11+/-10 U/ml, P<0.004) and sCD30
      plasma levels decreased to 95.2+/-109.6 U/ml after rhGH treatment. CONCLUSIONS:
      The finding that rhGH treatment decreased sCD30 plasma levels in children with
      CRF, and that children with primary GH deficiency had higher sCD30 plasma levels
      than controls, suggest that GH may regulate CD30 expression and possibly the
      balance of Th1/Th2. Whether the uraemia-induced increase in sCD30 is due to
      decreased renal excretion, to overproduction or both, remains to be determined.

PMID- 11522863
TI  - Measurement of blood urea concentration during haemodialysis is not an accurate
      method to determine equilibrated post-dialysis urea concentration.
AB  - BACKGROUND: The double-pool urea kinetic model requires the measurement of the
      blood urea concentrations 30 min after haemodialysis (C(t+30)) to calculate
      equilibrated Kt/V. However, it has been suggested that urea concentrations 30 min
      before the end of dialysis (C(t-30)) may be representative of C(t+30). The aim of
      this study was to validate this suggestion. METHODS: Twenty-two patients
      underwent haemodialysis for 180, 210, and 240 min. For each patient in each
      dialysis session, urea exponential decay curve was calculated. Because we
      measured C(t+30), we calculated the time (T(c)) before the end of dialysis that
      blood urea concentrations would be the same as C(t+30). In an additional 33
      patients, we measured blood urea concentrations at T(c) and in C(t+30). RESULTS:
      We found that C(t-30) was significantly lower than C(t+30) independent of the
      duration of dialysis. However, there was a significant correlation between Kt/V(t
      30) and Kt/V(t+30). The T(c) was 45 min before the end of dialysis. In the
      additional 33 patients, C(t-45) and C(t+30) were 54+/-17 and 52+/-17 mg/dl (NS),
      and Kt/V(t-45) and Kt/V(t+30) were 1.27+/-0.21 and 1.29+/-0.18 (NS),
      respectively. There were significant correlations between C(t-45) and C(t+30)
      (r=0.96; P<0.001), and between Kt/V(t-45) and Kt/V(t+30) (r=0.82; P<0.001).
      However, when measurements were analysed individually, 48% of the data points
      from C(t-45) vs C(t+30), and 42% of the data points from Kt/V(t-45) vs Kt/V(t+30)
      fell out of the 95% confidence interval of regression line. CONCLUSIONS: Although
      C(t-45) is useful to estimate Kt/V when assessing mean values, it is not suitable
      when assessing patients individually. This study demonstrates that the best
      method to calculate equilibrated Kt/V was a blood sample for urea concentrations
      30 min after haemodialysis.

PMID- 11522864
TI  - Erectile dysfunction and the effects of sildenafil treatment in patients on
      haemodialysis and continuous ambulatory peritoneal dialysis.
AB  - BACKGROUND: Sexual dysfunction, including erectile dysfunction, is common in
      patients with uraemia. Despite successful treatment of male sexual dysfunction
      with sildenafil in non-uraemic population, its efficacy in dialysis patients is
      unknown. PATIENTS AND METHODS: In this study, 35 male HD patients (mean age 48+/
      12 years) and 15 male CAPD patients (mean age 44+/-12 years) were included. In
      the baseline period, haemoglobin, serum urea, and albumin, Kt/V, several hormonal
      parameters, Beck depression scale, and penile Doppler blood flow, (peak systolic
      velocity after intracavernous papaverine administration) were measured. The
      international index of erectile function (IIEF) form was used to evaluate
      erectile dysfunction. Sildenafil was given to patients with erectile dysfunction
      at a dose of 50-100 mg/day twice a week. RESULTS: The percentage of erectile
      dysfunction was similar between patients on HD (71%) and those on CAPD (80%).
      Patients with erectile dysfunction were significantly older and had lower free
      testosterone serum levels and penile blood flow than those without. In linear
      regression analysis for baseline IIEF score, penile blood flow was the only
      independent variable associated with erectile dysfunction. IIEF score increased
      to a similar extent after sildenafil treatment in both HD patients (from 8.10+/
      5.54 to 21.70+/-9.61, P<0.001) and CAPD patients (from 9.90+/-3.87 to 21.60+/
      10.18, P=0.011). Changes in IIEF scores after sildenafil treatment were
      associated with baseline penile blood flow as an independent variable by linear
      regression analysis. Adverse events observed during sildenafil treatment were
      dyspepsia in two patients and headache in one patient. CONCLUSION: The rate of
      erectile dysfunction is high in dialysis patients. Penile blood flow is the most
      important factor for predicting both the development of erectile dysfunction and
      the response to sildenafil therapy in such patients. Oral sildenafil is an
      effective, reliable, well-tolerated treatment for uraemic patients with erectile
      dysfunction.

PMID- 11522865
TI  - Dialysis improves endothelial function in humans.
AB  - BACKGROUND: Circulating inhibitors of endothelial function have been implicated
      in the pathogenesis of vascular disease in chronic renal failure. The aim of this
      study was to determine if lowering the plasma concentration of these and other
      dialysable toxins improves endothelial function. To do this we compared the acute
      effects on endothelial function of single episodes of haemodialysis with
      automated peritoneal dialysis. We hypothesized that endothelial function would
      improve after dialysis, with a greater effect seen after haemodialysis due to
      more substantial clearance of endothelial toxins per-treatment. METHODS: Subjects
      with end-stage renal failure undergoing haemodialysis (n=16) or automated
      peritoneal dialysis (n=14) were investigated. Endothelial function was determined
      using vascular ultrasound to measure flow-mediated dilatation of the brachial
      artery and was compared with the dilatation caused by sublingual glyceryl
      trinitrate. Endothelial function was assessed before and after a single dialysis
      treatment. Plasma concentrations of the inhibitors of endothelial function,
      asymmetric dimethyl-l-arginine and homocysteine were measured. Flow-mediated
      dilatation was expressed as percentage change from basal diameter and analysed
      using Student's t test. RESULTS: The plasma concentration of circulating
      inhibitors of endothelial function was reduced after haemodialysis but not
      peritoneal dialysis. Haemodialysis increased flow-mediated dilatation from 4.0+/
      1.0% to 5.8+/-1.2% (P<0.002). These changes persisted for 5 h but returned to
      baseline by 24 h. Automated peritoneal dialysis had no acute effect on flow
      mediated dilatation (5.9+/-1.1% vs 5.4+/-0.8% after, P>0.5). There were no
      effects of either dialysis modality on dilatation to glyceryl trinitrate.
      CONCLUSIONS: Short-term reduction of circulating inhibitors of endothelial
      function by haemodialysis is associated with increased flow-mediated dilatation.
      These data suggest that dialysable endothelial toxins have deleterious effects on
      endothelial function that are rapidly reversible.

PMID- 11522866
TI  - Production of monokines in patients under polysulphone haemodiafiltration is
      influenced by the ultrafiltration flow rate.
AB  - BACKGROUND: Chronic haemodialysis patients show various clinical signs of
      immunodeficiency and there is growing evidence that a dysregulated monocyte
      cytokine production is heavily involved in this deficiency. The production of
      monokines in vitro has been proposed to correlate closely with the in vivo immune
      status and to be of high clinical relevance in cuprophane haemodialysis. Even
      though it is well known that the biocompatibility of dialyser membranes has a
      significant impact on immune functions, little is known about the influence of
      the ultrafiltration flow rate (UFR). The aim of this study was to investigate the
      potential long-term effects of UFR on the production of interleukin-10 (IL-10),
      interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) in an intra-individual
      study design. METHODS: In 11 patients previously treated with polysulphone
      haemodiafiltration, UFR was reduced from 40-46 ml/min to 24-28 ml/min, then to 7
      10 ml/min before it was reinstated at 40-46 ml/min for periods of 4 weeks each.
      Monokine secretion into culture supernatants and mRNA expression (assessed using
      a novel Taqman PCR technique), were determined in a whole blood assay after
      lipopolysaccharide stimulation. RESULTS: Reduction of UFR led to a significant
      increase in IL-10 secretion and mRNA expression (P=0.012, P=0.001). Conversely, a
      substantial (but not complete) decrease was observed when UFR returned to initial
      levels. In contrast, supernatant concentrations of IL-1beta (P=0.04) and IL-6
      (P=0.003), and mRNA expression of both monokines (P<0.001, P<0.001) decreased
      significantly when UFR was reduced. Calculation of the IL-1beta/IL-10 ratio also
      revealed a decrease when UFR was reduced, with an increase again being observed
      when the initial degree of UFR was reinstated (P<0.001). CONCLUSIONS: These
      results indicate a significant impact of UFR on the production of monokines at
      both the transcriptional and the protein level. We suggest that middle molecule
      removal has to be considered as a possible pathophysiological mechanism to
      explain our findings. Since monokine production in vitro was shown to be closely
      correlated with the in vivo immune status in patients on cuprophane
      haemodialysis, further investigations are necessary to clarify the impact of UFR
      on the immunocompetence of patients under polysulphone haemodiafiltration.

PMID- 11522867
TI  - High blood soluble receptor p80 for tumour necrosis factor-alpha is associated
      with erythropoietin resistance in haemodialysis patients.
AB  - BACKGROUND: Inflammation is one of the major causes of resistance to
      erythropoietin (rHuEpo) treatment. Tumour necrosis factor-alpha (TNF-alpha), one
      of the most potent proinflammatory cytokines, is known to inhibit human
      erythropoiesis directly in vitro. Although blood levels of soluble receptors for
      TNF-alpha (sTNFRs) are elevated in haemodialysis (HD) patients, the role of sTNFR
      for rHuEpo responsiveness in HD patients remains to be clarified. METHODS: We
      measured serum sTNFR (p55 and p80) levels in 83 stable outpatients undergoing
      regular HD (age 62+/-1, HD duration 15+/-1 years). After dividing the patients
      into three groups according to rHuEpo dose: (low (L) <60, n=31; moderate (M) > or
      =60 to <120, n=31; high (H) > or =120 U/kg/week rHuEpo, n=21), we examined the
      relationship between serum sTNFR levels and the degree of renal anaemia and
      rHuEpo dosage. RESULTS: Haemoglobin was significantly higher in patients
      receiving low rHuEpo dosage (L, 10.5+/-0.2; M, 9.7+/-0.1; H, 9.5+/-0.2 g/dl,
      P<0.01 vs M and H groups). There were no differences in blood TNF-alpha, sTNFR
      p55, C-reactive protein, albumin, ferritin, or intact parathyroid hormone levels
      among the three groups. Body mass index and creatinine generation rate, a marker
      of whole-body muscle volume, were significantly reduced in group H (P<0.01).
      Serum sTNFR p80 levels were significantly higher in group H (4.88+/-0.45 ng/ml)
      than in L (3.73+/-0.14 ng/ml) and M (3.67+/-0.21 ng/ml) groups (P<0.05). The
      blood interleukin (IL)-6 level was also increased in patients requiring high
      rHuEpo doses (L, 5.5+/-0.5; M, 6.4+/-0.5; H, 10.2+/-2.0 pg/ml, P<0.05 vs L and H
      groups). A stepwise regression analysis revealed that gender and sTNFR p80 were
      significant predictors of rHuEpo dosage. A significant direct relationship was
      found between rHuEpo dose and sTNFR p80 (r=0.499) and IL-6 (r=0.439) values in
      women (P<0.01) but not in men. CONCLUSIONS: These findings suggest that high
      blood sTNFR p80 may contribute to the development of rHuEpo resistance in female
      patients undergoing long-term HD.

PMID- 11522868
TI  - Long-term experience with the Thomas shunt, the forgotten permanent vascular
      access for haemodialysis.
AB  - BACKGROUND: Vascular access complications are the main cause of hospitalization
      in dialysis patients. The difficulty in creating and maintaining vascular access
      after several years on haemodialysis (HD) remains the primary problem in these
      patients. The femoro-femoral Thomas shunt is a permanent vascular access that was
      used in the 1970s and is all but forgotten at present. We analysed our experience
      with the Thomas shunt since 1979 in patients with no other possibility of regular
      vascular access. METHODS: We retrospectively studied 27 Thomas shunts implanted
      in 10 patients, aged 27-75 years at the time of first shunt implantation. Prior
      to implantation of the Thomas shunt, these patients had experienced 80 failed
      vascular accesses (plus four patients on CAPD), with an average of 8.6 accesses
      per patient. All Thomas shunts were implanted in femoral vessels. Clinical data
      were extracted from hospital and dialysis unit records and were analysed for
      efficacy, complications, and duration of patency. RESULTS: Total follow-up was
      1176 months, with an average shunt duration of 43.7 months (range 3-151 months).
      One-, 2-, 3- and 6-year survival rates were 85, 57, 49 and 25% respectively. Five
      patients spent more than 10 years on HD using the Thomas shunt, and one patient
      had the same unit for 12.5 years. A high blood flow (450 ml/min) was obtained,
      without recirculation, due to the characteristics of this shunt. Efficacy,
      measured as percentage urea reduction (PRU), was high (on average 77.8+/-1.5%).
      The infection incidence was one episode every 37.5 patient-months, Staphylococcus
      species being the most commonly isolated. There were no shunt removals because of
      infection. The most important cause of shunt withdrawal was thrombosis, with an
      incidence of one episode every 7 patient-months. Percutaneous angioplasty was
      successful in the majority of stenosis episodes. CONCLUSIONS: This study
      indicates that the Thomas shunt provides a good permanent vascular access for HD
      patients who have no other possibility of a regular vascular access. This shunt
      offers high dialysis efficacy without recirculation and an access duration
      comparable to AV fistulae. For these reasons the Thomas shunt should continue to
      be used as a vascular access in HD.

PMID- 11522869
TI  - Relationship between gastric emptying and clinical and biochemical factors in
      chronic haemodialysis patients.
AB  - BACKGROUND: Gastroparesis is an important side-effect of end-stage renal disease
      because of its influence on nutritional status. METHODS: In this study, 56
      equilibrated haemodialysis patients were evaluated by radioisotopic examination
      for gastric emptying time. These data were correlated to anthropometrical as well
      as biochemical parameters. RESULTS: The half-life time for gastric emptying was
      83+/-34 min in the overall population, compared to 50+/-15 min in a normal
      reference population. Prealbumin, mean fibular nerve-conduction velocity and
      intra- as well as extracorpuscular folic acid were significantly different
      between patients with the lowest and highest gastric emptying times. Linear
      correlation analysis between the half-life for residual radioactivity and the
      remaining parameters yielded a significant correlation for blood urea nitrogen,
      serum folic acid, intracorpuscular folic acid, serum vitamin B(12), serum C
      reactive protein, serum prealbumin and mean fibular nerve-conduction velocity.
      CONCLUSIONS: This study demonstrates that gastric emptying is significantly
      delayed in end-stage renal disease patients. The delay is associated with changes
      in biochemical indicators of nutritional status such as serum albumin and
      prealbumin.

PMID- 11522870
TI  - Oral supplementation of branched-chain amino acid improves nutritional status in
      elderly patients on chronic haemodialysis.
AB  - BACKGROUND: Anorexia may be associated with decreased plasma levels of branched
      chain amino acids (BCAA). In malnourished elderly haemodialysis (HD) patients,
      oral BCAA supplementation may improve anorexia, resulting in improved nutritional
      status. METHODS: Among 44 elderly (age >70 years) patients on chronic HD, 28
      patients with low plasma albumin concentration (<3.5 g/dl) were classified as the
      malnourished group; they also suffered from anorexia. The other 16 patients did
      not complain of anorexia and were classified as the well-nourished group. We
      performed a 12-month, placebo-controlled, double-blind study on the malnourished
      group. Fourteen patients each received daily oral BCAA supplementation (12 g/day)
      or a placebo in random order in a crossover trial for 6 months. Body fat
      percentage, lean body mass, plasma albumin concentration, dietary protein and
      caloric intakes, and plasma amino acid profiles were monitored. RESULTS: Lower
      plasma levels of BCAA and lower protein and caloric intakes were found in the
      malnourished group as compared to the well-nourished group. In BCAA-treated
      malnourished patients, anorexia and poor oral protein and caloric intakes
      improved within a month concomitant with the improvement in plasma BCAA levels
      over the values in well-nourished patients. After 6 months of BCAA
      supplementation, anthropometric indices showed a statistically significant
      increase and mean plasma albumin concentration increased from 3.31 g/dl to 3.93
      g/dl. After exchanging BCAA for a placebo, spontaneous oral food intake
      decreased, but the favourable nutritional status persisted for the next 6 months.
      In 14 patients initially treated with a placebo, no significant changes in
      nutritional parameters were observed during the first 6 months. However, positive
      results were obtained by BCAA supplementation during the subsequent 6 months, and
      mean plasma albumin concentration increased from 3.27 g/dl to 3.81 g/dl.
      CONCLUSIONS: Normalization of low plasma levels of BCAA by oral supplementation
      can reduce anorexia and significantly improve overall nutritional status in
      elderly malnourished HD patients.

PMID- 11522871
TI  - Effects of ultrapure dialysis fluid on nutritional status and inflammatory
      parameters.
AB  - BACKGROUND: Malnutrition and chronic systemic inflammatory response syndrome not
      only coexist in uraemia, but may also have a bi-directional cause-and-effect
      relationship. To evaluate the role of dialysate-related cytokine induction in
      inflammatory response and nutritional status, we conducted a prospective
      comparison of two dialysis fluids differing in their microbiological quality.
      METHODS: Forty-eight early haemodialysis patients were assigned to either
      treatment with conventional (potentially microbiologically contaminated) or on
      line produced ultrapure dialysis fluid. Study parameters were bacterial growth,
      markers of systemic inflammation (C-reactive protein (CRP) and interleukin 6),
      and parameters of nutritional status (estimated dry weight, upper mid-arm muscle
      circumference, serum albumin concentration, insulin-like growth factor 1, leptin,
      and protein catabolic rate). Patients were followed for 12 months. RESULTS: There
      were no statistically significant differences in demographic and treatment
      characteristics, degree of bacterial contamination of the dialysate, markers of
      systemic inflammation, or parameters of nutritional status among the two
      treatment groups at recruitment. Changing from conventional to ultrapure dialysis
      fluid reduced significantly the levels of IL-6 (19+/-3 pg/ml to 13+/-3 pg/ml) and
      CRP (1.0+/- 0.4 mg/dl to 0.5+/-0.2 mg/dl), and resulted in significant increases
      in estimated dry body weight, mid-arm muscle circumference, serum albumin
      concentration, levels of the humoral factors, and in protein catabolic rate after
      12 months. Continuous use of conventional dialysis fluid (median 40-60 c.f.u./ml)
      was not associated with significant alterations in markers of inflammation (IL-6
      21+/-4 pg/ml vs 24+/-6 pg/ml, CRP 0.9+/-0.3 mg/dl vs 1.1+/-0.4 mg/dl) or of
      nutritional status at any time of the study. All differences in systemic
      inflammation and nutritional parameters observed during the study period (from
      recruitment to month 12) were significant between the two patient groups.
      CONCLUSIONS: Cytokine induction by microbiologically contaminated dialysis fluid
      has a negative impact on nutritional parameters of early haemodialysis patients.
      The microbiological quality of the dialysis fluid represents an independent
      determinant of the nutritional status in addition to known factors, such as dose
      of dialysis and biocompatibility of the dialyser membrane. Ultrapure dialysis
      fluid adds to the cost of the dialytic treatment, but may improve the nutritional
      status in long-term haemodialysis patients.

PMID- 11522872
TI  - Sevelamer hydrochloride (Renagel), a non-calcaemic phosphate binder, arrests
      parathyroid gland hyperplasia in rats with progressive chronic renal
      insufficiency.
AB  - BACKGROUND: It has been demonstrated that dietary phosphate restriction
      suppresses parathyroid hormone (PTH) secretion and parathyroid cell proliferation
      in experimental animals with chronic renal insufficiency (CRI) independently of
      serum calcium and 1,25(OH)(2)D3 levels. This study was conducted to examine
      whether sevelamer hydrochloride (Renagel); hereafter referred to as sevelamer), a
      non-calcaemic phosphate binder could inhibit the parathyroid gland (PTG)
      hyperplasia in rats with progressive CRI. METHODS: Male Sprague-Dawley rats were
      injected twice with low doses of adriamycin (ADR). Two weeks after the last
      injection of ADR, rats were fed a diet containing 1 or 3% sevelamer for 84 days.
      Time course changes of serum levels of calcium, phosphorus, and PTH were
      measured. At the end of study, serum 1,25(OH)(2)D3 levels were measured and the
      maximal two-dimension area of the PTG in paraffin section was calculated using an
      imaging analyser. RESULTS: Dietary sevelamer treatment inhibited the elevations
      of serum phosphorus, calciumxphosphorus product, and PTH levels that occurred as
      the study progressed. Sevelamer also suppressed maximal PTG area and there
      existed positive strong correlation between maximal PTG area and serum PTH levels
      at the end of the study. Serum phosphorus levels positively correlated well with
      serum PTH levels and maximal PTG area. In contrast, serum calcium or
      1,25(OH)(2)D3 levels did not show any correlation with serum PTH levels and
      maximal PTG area. CONCLUSIONS: Sevelamer treatment arrested hyperphosphataemia
      and PTG hyperplasia accompanied by the elevation of serum PTH levels. The
      correlation analysis suggests that reduced serum phosphorus levels contributed to
      the suppression of PTG hyperplasia and resulted in the reduction of PTH levels in
      this animal model after the sevelamer treatment. The management of phosphorus
      control started from early stage of CRI could prevent PTG hyperplasia and
      facilitate later management of secondary hyperparathyroidism.

PMID- 11522873
TI  - A prospective crossover trial comparing intermittent intravenous and continuous
      oral iron supplements in peritoneal dialysis patients.
AB  - BACKGROUND: Concomitant iron supplementation is required in the great majority of
      erythropoietin (Epo)-treated patients with end-stage renal failure. Intravenous
      (i.v.) iron supplementation has been demonstrated to be superior to oral iron
      therapy in Epo-treated haemodialysis patients, but comparative data in iron
      replete peritoneal dialysis (PD) patients are lacking. METHODS: A 12-month,
      prospective, crossover trial comparing oral and i.v. iron supplementation was
      conducted in all Princess Alexandra Hospital PD patients who were on a stable
      dose of Epo, had no identifiable cause of impaired haemopoiesis other than
      uraemia, and had normal iron stores (transferrin saturation >20% and serum
      ferritin 100-500 mg/l). Patients received daily oral iron supplements (210 mg
      elemental iron per day) for 4 months followed by intermittent, outpatient i.v.
      iron infusions (200 mg every 2 months) for 4 months, followed by a further 4
      months of oral iron. Haemoglobin levels and body iron stores were measured
      monthly. RESULTS: Twenty-eight individuals were entered into the study and 16
      patients completed 12 months of follow-up. Using repeated-measures analysis of
      variance, haemoglobin concentrations increased significantly during the i.v.
      phase (108+/-3 to 114+/-3 g/l) compared with each of the oral phases (109+/-3 to
      108+/-3 g/l and 114+/-3 to 107+/-4 g/l, P<0.05). Similar patterns were seen for
      both percentage transferrin saturation (23.8+/-2.3 to 30.8+/-3.0%, 24.8+/-2.1 to
      23.8+/-2.3%, and 30.8+/-3.0 to 26.8+/-2.1%, respectively, P<0.05) and ferritin
      (385+/-47 to 544+/-103 mg/l, 317+/-46 to 385+/-47 mg/l, 544+/-103 to 463+/-50
      mg/l, respectively, P=0.10). No significant changes in Epo dosages were observed
      throughout the study. I.v. iron supplementation was associated with a much lower
      incidence of gastrointestinal disturbances (11 vs 46%, P<0.05), but exceeded the
      cost of oral iron treatment by 6.5-fold. CONCLUSIONS: Two-monthly i.v. iron
      infusions represent a practical alternative to oral iron and can be safely
      administered to PD patients in an outpatient setting. Compared with daily oral
      therapy, 2-monthly i.v. iron supplementation in PD patients was better tolerated
      and resulted in superior haemoglobin levels and body iron stores.

PMID- 11522874
TI  - Effects of glucose dialysate on extracellular matrix production by human
      peritoneal mesothelial cells (HPMC): the role of TGF-beta.
AB  - BACKGROUND: Dialysate glucose has been implicated in the loss of peritoneal
      membrane function seen in long-term CAPD patients. METHODS: In order to
      investigate this in vitro, human peritoneal mesothelial cells (HPMC) were
      cultured in a 50:50 mix of dialysis solution and M199 for 12 h. The dialysate was
      laboratory manufactured and designed to be identical in composition to PD4 (LAB).
      The final glucose concentration ranged between 5 and 40 mmol/l. Experiments were
      conducted in the presence and absence of an anti-transforming growth factor-beta
      (TGF-beta) antibody. Cell viability was measured by lactate dehydrogenase (LDH)
      release. Fibronectin (FN) and TGF-beta protein were measured by ELISA, and FN
      gene expression was measured by Northern analysis. Separately, the effects of
      recombinant TGF-beta(1) added to M199: dialysate at 5 mmol/l glucose were
      investigated. RESULTS: Forty millimoles per litre d-glucose LAB caused a decrease
      in cell viability, as evidenced by an increase in LDH release (6.0+/-1.3 vs 2.6+/
      0.7%). This effect was dependent on osmolality. Forty millimoles per litre d
      glucose LAB stimulated a 15.4+/-4.6% increase in FN, a 46.5+/-18.3% increase in
      TGF-beta protein (both P<0.05), and 1.4+/-0.09-fold increase in FN mRNA compared
      with 5 mmol/l d-glucose LAB. Exogenous TGF-beta 0-1 ng/ml induced a dose
      dependent increase in FN protein (280+/-45% increase at TGF-beta 1 ng/ml,
      P<0.0001), and FN mRNA levels (10.0+/-1.8-fold at TGF-beta 1 ng/ml). The increase
      in FN in response to 40 mmol/l glucose was significantly reduced by anti-TGF-beta
      antibody to levels not different from control (93.8+/-6.6%, P<0.05 vs no Ab).
      CONCLUSIONS: These data suggest that the pro-fibrotic effect of glucose dialysate
      on HPMC is mediated through stimulation of TGF-beta, which promotes FN gene
      expression and protein production.

PMID- 11522875
TI  - Technical survival of CAPD catheters: comparison between percutaneous and
      conventional surgical placement techniques.
AB  - BACKGROUND: Percutaneous peritoneal dialysis catheter (PDC) placement is a well
      tolerated, rapidly performed bedside procedure that allows a rapid initiation of
      CAPD. We compared the technical survival of PDCs while comparing the mode of
      insertion. METHODS: We retrospectively reviewed 215 PDCs inserted over a 60-month
      period in 191 patients on CAPD therapy. Of these, 133 were placed percutaneously
      by nephrology staff (group P) and 82 were placed using conventional surgical
      techniques by surgical staff (group S). The total experience accumulated was 4000
      patient-months: 2260 patient-months in group P and 1740 patient-months in group
      S. RESULTS: The incidence of complications in PDCs did not differ between the
      groups (1 episode/33 patient-months in group P and 1 episode/29 patient-months in
      group S). Two episodes of early leakage and 9 episodes of late leakage were
      observed in group P compared with one early leakage and 4 episodes of late
      leakage in group S. Of the mechanical complications in group P, 8.86% were due to
      catheter malfunction, including catheter tip migration and obstruction, compared
      with 12.63% in group S. The incidence of catheter infections was 1 episode/73
      patient-months in group P and 1 episode/62 patient-months in group S.
      Significantly more catheters were removed in group S compared with group P (40%
      vs 16%, P<0.001). One-year and 2-year technical survivals were 90% and 82% in
      group P, and 73% and 60% in group S (P=0.0032), respectively. CONCLUSIONS:
      Percutaneous bedside placement of PDCs by nephrologists provides a safe and
      reliable access for peritoneal dialysis.

PMID- 11522876
TI  - Helical CT angiography in evaluation of live kidney donors.
AB  - BACKGROUND: Live kidney donor evaluation mandates anatomical and functional
      assessment of the donor kidney. Helical computed tomography (CT) with advanced 3
      D techniques provides detailed description of the vascular, parenchymal, and
      collecting system. METHODS: We compared the accuracy of helical CT angiography
      with intra-operative findings in the evaluation of 102 live kidney donors.
      RESULTS: Identification of vascular anomalies was best on direct viewing of the
      axial images using interactive scrolling through the images and cine-loop paging.
      In 204 kidneys evaluated, a single renal artery was present in 74.5% and a single
      renal vein in 87.5%. Multiple renal arteries were more common on the left side
      (31%) vs the right side (20%). Early branching of the arteries was seen with
      equal frequency (approximately equal to 10%) on either side. Multiple renal veins
      were more often on the right side (20%) vs the left side (5%), and one patient
      was found to have double inferior vena cava. CT angiographic findings were
      concordant with the intra-operative findings in 97% of the cases, missing a small
      renal vein, an accessory artery that was visualized in retrospect, and a very
      early branch that was read as accessory artery. CT also revealed cortical cysts
      (four cases), duplex collecting system (two cases), hydronephrosis (one case),
      renal stone (one case), and liver haemangioma (two cases). CONCLUSION: CT
      angiography is highly accurate for detecting vascular anomalies, and providing
      anatomical information. It may serve as the primary tool for donor evaluation.

PMID- 11522877
TI  - Low tacrolimus concentrations and increased risk of early acute rejection in
      adult renal transplantation.
AB  - BACKGROUND: A retrospective analysis was performed on adult renal transplant
      recipients to evaluate the relationship between tacrolimus trough concentrations
      and the development of rejection in the first month after transplant. METHODS: A
      total of 349 concentrations from 29 patients, measured by enzyme-linked
      immunosorbent assay (ELISA), were recorded. Based on an increased serum
      creatinine, 12 patients were considered to have organ rejection. Rejection was
      confirmed by biopsy in five of these. The median trough concentration of
      tacrolimus over the first month of therapy, or until the time of first rejection
      was compared in rejecters vs non-rejecters. RESULTS: Median trough concentrations
      of tacrolimus were found to be lower in biopsy-proven rejecters vs non-rejecters
      (P=0.03) and all rejecters vs non-rejecters (P=0.04). The average median
      concentration (+/-SD) in the biopsy-proven rejecter group was 5.09+/-1.16 ng/ml,
      compared to 9.20+/-3.52 ng/ml in the non-rejecter group. After exclusion of an
      outlier, the average median concentration in all rejecters was 5.57+/-1.47 ng/ml,
      compared with 9.20+/-3.52 ng/ml in non-rejecters. A rejection rate of 55% was
      found for patients with a median trough concentration between 0 and 10 ng/ml.
      This compared with no observed rejection in patients with a median concentration
      between 10 and 15 ng/ml. CONCLUSION: A significant relationship exists between
      organ rejection and median tacrolimus trough concentrations in the first month
      post-transplant, with patients displaying low concentrations more likely to
      reject. In order to minimize rejection in the first month after renal
      transplantation, trough concentrations greater than 10 ng/ml must be achieved.

PMID- 11522878
TI  - Association of mesangial IgM with IgM deposits in the macula densa: an indication
      of non-specific macromolecule transport rather than immune reactant?
AB  - BACKGROUND: We observed IgM deposits in the macula densa of the distal convoluted
      tubule in some renal biopsies with mesangial IgM deposits and did a systematic
      study to investigate the frequency of this phenomenon. We compared the findings
      with those in IgA disease. METHODS: A total of 30 renal biopsies with either
      isolated predominantly mesangial IgM, or mesangial IgA (+/-IgM) deposition, were
      retrieved from the files and reviewed independently by both authors. RESULTS:
      Eight showed strong macula densa IgM deposits and another three showed weak
      deposits in the macula densa on immunoperoxidase staining. A total of 14 biopsies
      also showed mesangial IgA deposition but IgA was not seen in the macula densa.
      CONCLUSIONS: These results confirm the association of IgM deposits in the macula
      densa with mesangial IgM, and suggest that mesangial IgM deposits may be a
      reflection of non-specific macromolecule transport rather than an immune
      reactant.

PMID- 11522879
TI  - Effect of acetate-free biofiltration on the anaemia of haemodialysis patients: a
      prospective cross-over study.
AB  - BACKGROUND: The discussion about the pathogenesis of renal anaemia, whether it is
      primarily due to relative erythropoietin (Epo) deficiency or to uraemic
      inhibition of erythropoiesis, is still open. Although it has so far not been
      possible to identify or isolate a substance retained in uraemia with a
      suppressive action directed specifically against red-cell production, dialysis
      therapy can improve the effect of both residual endogenous Epo and exogenous
      rHuEpo. To what extent the mode and/or the dose of dialysis influence Epo
      efficacy is as yet poorly understood. METHODS: This study was performed as a
      single-centre trial. The protocol included a run-in period of 4 months followed
      by a prospective cross-over study including 6 months each of acetate-free
      biofiltration (AFB) with a high-flux biocompatible membrane and standard
      bicarbonate dialysis (BD) with a low-flux cellulosic membrane in a random
      sequence. AFB is a haemodiafiltration technique based on a continuous post
      dilution infusion of a sterile isotonic bicarbonate solution. At the start of the
      run-in period (and for the entire length of the study), rHuEpo administration was
      withdrawn; patients whose haemoglobin (Hb) levels dropped at a level <8.0 g/dl at
      one single monthly check, had to be withdrawn from the study. A blood sample was
      collected every month for the blood gas analysis and for the determination of
      blood urea nitrogen, serum creatinine, sodium, potassium, calcium, phosphorus,
      Hb, erythrocyte, reticulocyte, leukocyte and thrombocyte cell counts, mean
      globular volume and haematocrit. An equilibrated single pool Kt/V(urea)>1.2 was
      mandatory in both treatment modalities. Serum iron, total iron-binding capacity,
      and ferritin were checked every 3 months. RESULTS: Twenty-three of 137
      haemodialysis patients were considered eligible for the trial on the basis of the
      entry criteria. Of these, 15 volunteered and only 10 completed the study. No
      significant differences in the haematological indices, in the biochemical
      parameters assessing body iron stores, or in i.v. iron dosage was observed when
      comparing AFB with BD treatments. The equilibrated single pool Kt/V(urea) was
      always >1.2 and in no case was a significant difference observed when comparing
      AFB with BD treatments. Treatment time was significantly different between the
      two treatments (262+/-2 min in BD and 249+/-1 in AFB, P<0.0001). Neither pre- nor
      post-dialysis systolic and diastolic blood pressures, pre-dialysis serum
      bicarbonate and pH, pre-dialysis serum sodium, potassium, calcium, or phosphorus
      were significantly different when comparing the two treatment modalities. All 10
      patients completed the 1-year follow-up without any major side-effects.
      CONCLUSIONS: Our study did not show any improvement of anaemia when treating a
      highly selected patient group, in the absence of any Epo therapy, with AFB
      compared with standard BD. Even though these conclusions cannot be extended in
      toto to the entire dialysis population, in which there is a large proportion of
      Epo-treated patients with Hb levels around 11 g/dl, we may nevertheless conclude
      that when patients are well selected, adequately dialysed, and not iron- and/or
      vitamin-depleted, the effect of a haemodiafiltration technique with a high-flux
      biocompatible membrane is less than might be expected from the results of
      uncontrolled studies.

PMID- 11522880
TI  - Atorvastatin improves endothelial function in renal-transplant recipients.
AB  - BACKGROUND: Hyperlipidaemia and endothelial dysfunction are common features in
      cyclosporin A (CsA)-treated renal transplant recipients. Endothelial dysfunction
      may contribute to the risk of premature atherosclerosis and cardiovascular death
      in these patients. A beneficial effect of statin therapy beyond cholesterol
      lowering may be an improvement of endothelial function. The present study was
      designed to assess the effect of atorvastatin on serum lipids and endothelial
      function in CsA treated renal transplant recipients. METHODS: This pilot study
      was an open trial of 4 weeks atorvastatin (10 mg per day) treatment in renal
      transplant recipients (n=22). All patients received a CsA- and prednisolone-based
      immunosuppressive regimen. Endothelial function was assessed in the forearm skin
      microvasculature by acetylcholine stimulation and laser Doppler flowmetry, before
      and after atorvastatin treatment. Serum lipids, plasma endothelin-1 (ET-1),
      nitric oxide (NO), and von Willebrand factor (vWF) were also measured. RESULTS:
      Both total and LDL cholesterol were significantly reduced by 26.8 +/- 8.4 and
      41.5 +/- 11.0% respectively, after 4 weeks of treatment. Endothelial function was
      significantly improved during atorvastatin treatment, area under the flux versus
      time curve (AUC)(ACh) was 538 +/- 362 AU x min before and 682 +/- 276 AU x min
      after treatment (P=0.042). Plasma NO levels also showed a borderline significant
      increase from 49 +/- 30 to 57 +/- 37 micromol/l during the treatment period
      (P=0.051), though plasma ET-1 (0.37+/-0.08 vs 0.37+/-0.12 fmol/ml) and vW (196+/
      57 vs 197+/-37%) were unchanged. CONCLUSION: Atorvastatin lowered serum
      cholesterol significantly and improved endothelial function in renal transplant
      recipients after 4 weeks of treatment. Plasma NO levels were increased during
      atorvastatin treatment, indicating a possible endothelial protective effect
      through an "endothelial-NO pathway".

PMID- 11522881
TI  - Conversion between bromcresol green- and bromcresol purple-measured albumin in
      renal disease.
AB  - BACKGROUND: Albumin measured by a bromcresol purple dye-binding assay (Alb(BCP))
      agrees more closely with the gold standard of immunonephelometry than does
      bromcresol green (Alb(BCG)) measurement. Both tests are in current clinical use.
      A method for converting between the two would be useful. METHODS: We measured
      albumin by bromcresol green and bromcresol purple in 535 patients, 155 of whom
      had renal disease. We randomly divided data from the patients with renal disease
      into two equal-sized sets, and used one set to derive, and the remaining set to
      validate, a regression equation relating the two values. RESULTS: The
      relationship Alb(BCG)=5.5+Alb(BCP) performed very well in both the renal patient
      validation set and in the data from 380 unselected in-patients and out-patients.
      Intraclass correlations for agreement between measured Alb(BCG) and predicted
      Alb(BCG) was 0.98 in both analyses. CONCLUSIONS: The ability to convert between
      these measurements will be of use in clinical situations where the absolute value
      of the serum albumin is important, when data from laboratories using different
      methodologies must be combined, and in the application of the Modification of
      Diet in Renal Disease formula to estimate glomerular filtration rate in patients
      whose albumin has been measured by bromcresol purple.

PMID- 11522882
TI  - Acute pancreatitis in a patient with partial lipodystrophy and
      membranoproliferative glomerulonephritis.

PMID- 11522883
TI  - Henoch-Schonlein purpura with IgG PR3-ANCA in a PiZZ alpha 1-antitrypsin
      deficient patient.

PMID- 11522884
TI  - Porphyria cutanea tarda precipitated by intravenous iron in a haemodialysis
      patient.

PMID- 11522885
TI  - Light chain deposit disease: a frequent cause of diagnostic difficulty.

PMID- 11522886
TI  - A child with polycystic kidney disease: do we have to care about associated
      malformations?

PMID- 11522887
TI  - Light from the renal biopsy.

PMID- 11522888
TI  - Diabetes mellitus, arterial hypertension and hilar adenopathy.

PMID- 11522889
TI  - Just another urinary tract infection?

PMID- 11522890
TI  - Acute renal failure in the nephrotic syndrome.

PMID- 11522891
TI  - Recurrent Goodpasture's disease with severe renal involvement after initial
      successful treatment.

PMID- 11522892
TI  - A hypothesis for endogenous opioid peptides in uraemic pruritus: role of
      enkephalin.

PMID- 11522893
TI  - Differential manipulation of the renin angiotensin system and epoietin
      requirements in maintenance haemodialysis patients.

PMID- 11522894
TI  - Anaphylactic reaction during haemodialysis on AN69 membrane in a patient
      receiving angiotensin II receptor antagonist.

PMID- 11522895
TI  - Olecranon bursitis in chronic haemodialysis patients.

PMID- 11522896
TI  - Comparison of peritonitis incidence in CAPD and automated peritoneal dialysis.

PMID- 11522897
TI  - Laryngeal tuberculosis with tongue involvement in a renal transplant recipient.

PMID- 11522898
TI  - Tumour-like calcinosis causing reversible tetraparesis in a patient on continuous
      ambulatory peritoneal dialysis.

PMID- 11522899
TI  - Pseudomembraneous colitis under therapy with mycophenolate mofetil following
      pancreas-kidney double transplantation.

PMID- 11522903
TI  - Structure and function of heterotrimeric G proteins in plants.
AB  - Heterotrimeric G proteins are mediators that transmit the external signals via
      receptor molecules to effector molecules. The G proteins consist of three
      different subunits: alpha, beta, and gamma subunits. The cDNAs or genes for all
      the alpha, beta, and gamma subunits have been isolated from many plant species,
      which has contributed to great progress in the study of the structure and
      function of the G proteins in plants. In addition, rice plants lacking the alpha
      subunit were generated by the antisense method and a rice mutant, Daikoku d1, was
      found to have mutation in the alpha-subunit gene. Both plants show abnormal
      morphology such as dwarfism, dark green leaf, and small round seed. The findings
      revealed that the G proteins are functional molecules regulating some body plans
      in plants. There is evidence that the plant G proteins participate at least in
      signaling of gibberellin at low concentrations. In this review, we summarize the
      currently known information on the structure of plant heterotrimeric G proteins
      and discuss the possible functions of the G proteins in plants.

PMID- 11522904
TI  - Guard-cell chloroplasts provide ATP required for H(+) pumping in the plasma
      membrane and stomatal opening.
AB  - To elucidate the role of guard-cell chloroplasts (GCCs) in stomatal movement, we
      investigated the effects of oligomycin, an inhibitor of oxidative
      phosphorylation, and 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU), an inhibitor
      of photosystem II, on fusicoccin (FC)-induced H(+) pumping and stomatal opening.
      FC was found to induce H(+ )pumping in guard-cell protoplasts (GCPs) from Vicia
      faba and stomatal opening in the epidermis of Commelina benghalensis; and, red
      light (RL) slightly stimulated these responses. Oligomycin strongly inhibited the
      pumping and stomatal opening in the dark. RL partially reversed the inhibitions,
      and DCMU decreased the effect of RL. FC activated the plasma membrane H(+)-ATPase
      (EC 3.6.1.35) in GCPs similarly irrespective of these treatments, indicating that
      the H(+)-ATPase activity was not the limiting step in H(+) pumping. Oligomycin
      significantly decreased the ATP content in GCPs in the dark. RL partially
      reversed this effect, and DCMU eliminated the effect of RL. A significant part of
      the ATP produced by photophosphorylation to H(+) pumping was indicated under RL.
      These results suggest that GCCs supply ATP to the cytosol under RL, and that the
      ATP is utilized by the plasma membrane H(+)-ATPase for H(+) pumping.

PMID- 11522905
TI  - Photoinhibition and light-induced cyclic electron transport in ndhB(-) and psaE(
      ) mutants of Synechocystis sp. PCC 6803.
AB  - The ndhB(-) and psaE(-) mutants of the cyanobacterium Synechocystis sp. PCC 6803
      are partly deficient in PSI-driven cyclic electron transport. We compared
      photoinhibition in these mutants to the wild type to test the hypothesis that PSI
      cyclic electron transport protects against photoinhibition. Photoinhibitory
      treatment greatly accelerated PSI cyclic electron transport in the wild type and
      also in both the mutants. The psaE(-) mutant showed rates of PSI cyclic electron
      transport similar to the wild type under all conditions tested. The ndhB(-)
      mutant showed much lower rates of PSI cyclic electron transport than the wild
      type following brief dark adaptation but exceeded wild type rates after exposure
      to photoinhibitory light. The wild type and both mutants showed similar rates of
      photoinhibition damage and photoinhibition repair at PSII. Photoinhibition at PSI
      was much slower than at PSII and was also similar between the wild type and both
      mutants, despite the known instability of PSI in the psaE(-) mutant. We conclude
      that photoinhibitory light induces sufficient PSI-driven cyclic electron
      transport in both the ndhB(-) and psaE(-) mutants to fulfill any role that cyclic
      electron transport plays in protection against photoinhibition.

PMID- 11522906
TI  - The transcriptional activation domain of the plant-specific Dof1 factor functions
      in plant, animal, and yeast cells.
AB  - Maize Dof1, one of the plant-specific Dof transcription factors, is involved in
      light-regulated gene expression. To elucidate the molecular mechanism underlying
      the activity of Dof1, in vivo functional analyses were carried out using
      transient expression assays with maize mesophyll protoplasts. The results suggest
      that the Dof domain alone, the region conserved among Dof factors, can mediate
      interaction with DNA in vivo and distinct Dof1 activities in greening and
      etiolated protoplasts. A region rich in basic amino acids was identified as a
      nuclear localization signal. Deletion analysis defined the transcriptional
      activation domain of 48 amino acids located in the C-terminus of Dof1. This
      activation domain was also found to be functional in both human cells and yeast,
      implying that Dof1 may stimulate transcription through a mechanism evolutionarily
      conserved among eukaryotes. A computer homology search with known transcription
      factors revealed that the activation domain of Dof1 displayed only a limited
      similarity to Activation domain II of animal transcription factor GATA-4.
      Mutational analysis revealed the critical role of a tryptophan residue within the
      activation domain of Dof1, as had been shown in Activation domain II of GATA-4.

PMID- 11522907
TI  - Iron-binding activity of FutA1 subunit of an ABC-type iron transporter in the
      cyanobacterium Synechocystis sp. Strain PCC 6803.
AB  - The futA1 (slr1295) and futA2 (slr0513) genes encode periplasmic binding proteins
      of an ATP-binding cassette (ABC)-type iron transporter in Synechocystis sp. PCC
      6803. FutA1 was expressed in Escherichia coli as a GST-tagged recombinant protein
      (rFutA1). Solution containing purified rFutA1 and ferric chloride showed an
      absorption spectrum with a peak at 453 nm. The absorbance at this wavelength rose
      linearly as the amount of iron bound to rFutA1 increased to reach a plateau when
      the molar ratio of iron to rFutA1 became unity. The association constant of
      rFutA1 for iron in vitro was about 1 x 10(19). These results demonstrate that the
      FutA1 binds the ferric ion with high affinity. The activity of iron uptake in the
      Delta futA1 and Delta futA2 mutants was 37 and 84%, respectively, of that in the
      wild-type and the activity was less than 5% in the Delta futA1/Delta futA2 double
      mutant, suggesting their redundant role for binding iron. High concentrations of
      citrate inhibited ferric iron uptake. These results suggest that the natural iron
      source transported by the Fut system is not ferric citrate.

PMID- 11522908
TI  - Effects of Ca(2+) and calmodulin on the motile activity of characean myosin in
      vitro.
AB  - It is well known that the cytoplasmic streaming of characean cells is readily
      inhibited by Ca(2+). However, neither the actin-activated MgATPase nor the in
      vitro motile activity of purified characean myosin were inhibited by Ca(2+).
      Recently, amino acid sequence of characean myosin was determined in our
      laboratory and the sequence revealed that characean myosin contains six
      calmodulin binding sites in the neck region. We also detected calmodulin in
      quickly prepared characean myosin fraction. It is, therefore, possible that the
      insensitivity of characean myosin to Ca(2+) is due to the dissociation of some
      calmodulin molecules from the neck region during the course of protein
      purification. To determine strictly the Ca(2+) sensitivity of characean myosin,
      we intentionally used crude preparation of characean myosin to reduce the
      possibility of calmodulin dissociation and examined the motile activity of
      characean myosin in vitro in the presence of excess characean calmodulin. We
      could not observe any drastic inhibition of characean myosin activity by Ca(2+).
      The results suggest that the brief cessation of cytoplasmic streaming is not
      caused by the direct inhibition of myosin activity by Ca(2+).

PMID- 11522909
TI  - Developmental analysis of a putative ATP/ADP carrier protein localized on
      glyoxysomal membranes during the peroxisome transition in pumpkin cotyledons.
AB  - In order to clarify the peroxisomal membrane proteins (PMPs), we characterized
      one of the major PMPs, PMP38. The deduced amino acid sequence for its cDNA in
      Arabidopsis thaliana contained polypeptides with 331 amino acids and had high
      similarity with those of Homo sapiens PMP34 and Candida boidinii PMP47 known as
      homologues of mitochondrial ATP/ADP carrier protein. We expected PMP38 to be
      localized on peroxisomal membranes, because it had the membrane peroxisomal
      targeting signal. Cell fractionation and immunocytochemical analysis using
      pumpkin cotyledons revealed that PMP38 is localized on peroxisomal membranes as
      an integral membrane protein. The amount of PMP38 in pumpkin cotyledons increased
      and reached the maximum protein level after 6 d in the dark but decreased
      thereafter. Illumination of the seedlings caused a significant decrease in the
      amount of the protein. These results clearly showed that the membrane protein
      PMP38 in glyoxysomes changes dramatically during the transformation of
      glyoxysomes to leaf peroxisomes, as do the other glyoxysomal enzymes, especially
      enzymes of the fatty acid beta-oxidation cycle, that are localized in the matrix
      of glyoxysomes.

PMID- 11522910
TI  - Inhibition of photosystems I and II and enhanced back flow of photosystem I
      electrons in cucumber leaf discs chilled in the light.
AB  - Pre-illumination of cucumber leaf discs at a chilling temperature in low
      irradiance white light resulted in accelerated re-reduction of P700(+) [the
      special Chl pair in the photosystem I (PSI) reaction centre] when the far-red
      measuring light was turned off. Measurements (in +/- methyl viologen or +/- DCMU
      conditions) of the re-reduction half time suggest that accelerated re-reduction
      of P700(+) appeared to be predominantly due to charge recombination and only
      partly due to reductants sustained by previous cyclic electron flow around PSI.
      Apparently, charge recombination in PSI was greatly enhanced by inhibition of
      forward, linear electron flow. Inhibition of PSII electron transport was observed
      to occur to a lesser extent than that of PSI, but only if the measurement of PSII
      functionality was free from complications due to downstream accumulation of
      electrons in pools. We suggest that promotion of controlled charge recombination
      and cyclic electron flow round PSI during chilling of leaves in the light may
      partly prevent further damage to both photosystems.

PMID- 11522911
TI  - Identification of Lhcb gene family encoding the light-harvesting chlorophyll-a/b
      proteins of photosystem II in Chlamydomonas reinhardtii.
AB  - The Lhcb gene family in green plants encodes several light-harvesting Chl a/b
      binding (LHC) proteins that collect and transfer light energy to the reaction
      centers of PSII. We comprehensively characterized the Lhcb gene family in the
      unicellular green alga, Chlamydomonas reinhardtii, using the expressed sequence
      tag (EST) databases. A total of 699 among over 15,000 ESTs related to the Lhcb
      genes were assigned to eight, including four new, genes that we isolated and
      sequenced here. A sequence comparison revealed that six of the Lhcb genes from C.
      reinhardtii correspond to the major LHC (LHCII) proteins from higher plants, and
      that the other two genes (Lhcb4 and Lhcb5) correspond to the minor LHC proteins
      (CP29 and CP26). No ESTs corresponding to another minor LHC protein (CP24) were
      found. The six LHCII proteins in C. reinhardtii cannot be assigned to any of the
      three types proposed for higher plants (Lhcb1-Lhcb3), but were classified as
      follows: Type I is encoded by LhcII-1.1, LhcII-1.2 and LhcII-1.3, and Types II,
      III and IV are encoded by LhcII-2, LhcII-3 and LhcII-4, respectively. These
      findings suggest that the ancestral LHC protein diverged into LHCII, CP29 and
      CP26 before, and that LHCII diverged into multiple types after the phylogenetic
      separation of green algae and higher plants.

PMID- 11522912
TI  - Short- and long-term effects of dehydroascorbate in Lupinus albus and Allium cepa
      roots.
AB  - Administration of 1 mM dehydroascorbate (DHA) results in a rapid and large
      increase in cellular ascorbate (AA) content in both Lupinus albus L. and Allium
      cepa L. root tips. Uptake of DHA from the medium occurs at a high rate within 10
      12 h of incubation, and is slowed down thereafter. In the first few h, DHA
      reduction to AA is apparently correlated to GSH depletion and slightly higher DHA
      reductase activity. DHA incubation also seems to induce new GSH synthesis. Longer
      DHA incubation (24 h) affects root growth by inhibiting cell proliferation. At
      this stage, an apparently generalised oxidation of SH-containing proteins is
      observed in DHA-treated roots. Treatment with 1 mM L-galactono-gamma-lactone, the
      last precursor of AA biosynthesis, results in an increase in AA content similar
      to that obtained with DHA, but stimulates growth and affects the redox state of
      SH-containing proteins in the opposite way. A possible multi-step mechanism of
      DHA reduction/removal is suggested and the hypothesis that DHA inhibits cell
      cycle progression by affecting the redox state of SH-containing proteins is
      discussed.

PMID- 11522913
TI  - Partial characterization of farnesyl and geranylgeranyl diphosphatases induced in
      rice seedlings by UV-C irradiation.
AB  - This study reports the identification and characterization of allyl
      diphosphatases (EC 3.1.7.1) in plants by using rice seedlings. Two distinct
      Mg(2+)-independent allyl diphosphatases, which convert farnesyl diphosphate (FDP)
      and geranylgeranyl diphosphate (GGDP) into farnesol and geranylgeraniol,
      respectively, were induced in rice seedlings irradiated with UV-C. Farnesyl
      diphosphatase (FDPase) and geranylgeranyl diphosphatase (GGDPase) are located in
      the microsomal fraction. The relative specific activity of FDPase was much higher
      than the specific activity of GGDPase. FDPase activity was inhibited by GGDP (50%
      inhibition at 5 microM) and geranyl diphosphate (50% inhibition at 100 microM).
      In contrast, GGDPase activity was inhibited 50% by 50 microM isopentenyl
      diphosphate or 100 microM FDP. The optimal pH for FDPase was 6.3 and for GGDPase
      was 7.9.

PMID- 11522914
TI  - Inhibition of the light-independent synthesis of chlorophyll in pine cotyledons
      at low temperature.
AB  - Cotyledons of Japanese black pine (Pinus thunbergii) were yellow when they
      developed in darkness at 8 degrees C since the light-independent synthesis of
      chlorophyll was almost completely inhibited in these cotyledons. The level of
      chlorophyll in dark-grown cotyledons was less than one-twentieth of that in light
      grown cotyledons at the same temperature. In the yellow cotyledons, levels of
      transcripts of cab, rbcS, rbcL and psbA genes were quite high. The large and
      small subunits of ribulose-1,5-bisphosphate carboxylase/oxygenase were also
      detected at relatively high levels in yellow cotyledons. However, the
      accumulation of the two apoproteins of the light-harvesting chlorophyll a/b
      binding protein of PSII was limited because of the limited supply of chlorophyll.

PMID- 11522915
TI  - Localization of CYP86B1 in the outer envelope of chloroplasts.
AB  - CYP86B1 was cloned from a cDNA library and the protein expressed in E. coli. The
      protein gave the expected carbon monoxide difference spectrum. Using in vitro
      import assays with isolated pea chloroplasts, CYP86B1 was shown to be associated
      with the outer chloroplastic envelope membrane. This study provides the first
      direct evidence for a chloroplast-localized cytochrome P450-dependent
      monooxygenase.

PMID- 11522916
TI  - Redox changes accompanying the degradation of seed storage proteins in
      germinating rice.
AB  - The mobilization of storage proteins (glutelins) in germinating rice seeds was
      accompanied by an ordered sequential combination of proteolysis and reduction of
      disulfide groups. Mobilization was followed by application of non
      reducing/reducing two dimensional-PAGE after monobromobimane labeling of the
      sulfhydryl groups of the proteins in intact seeds.

PMID- 11522917
TI  - Sequence-based detection of distantly related proteins with the same fold.

PMID- 11522918
TI  - A numerical measure of amino acid residues similarity based on the analysis of
      their surroundings in natural protein sequences.
AB  - A measure of similarity between amino acid residues based on the analysis of the
      surroundings of each residue in primary structures of native proteins is
      proposed. The statistical data used for this purpose were obtained from the
      analysis of 168,808 protein sequences, which comprise the Protein Identification
      Research database (release 63). Using various threshold values of the proposed
      measure, amino acid residues were classified into several groups. The
      classification elaborated differs essentially from groupings previously used. The
      numerical measure of amino acid residues similarity can be used in site-directed
      mutagenesis studies for the prediction of probability of local spatial
      rearrangements in proteins.

PMID- 11522919
TI  - A Web-based classification system of DNA-binding protein families.
AB  - Rational classification of proteins encoded in sequenced genomes is critical for
      making the genome sequences maximally useful for functional and evolutionary
      studies. The family of DNA-binding proteins is one of the most populated and
      studied amongst the various genomes of bacteria, archaea and eukaryotes and the
      Web-based system presented here is an approach to their classification. The
      DnaProt resource is an annotated and searchable collection of protein sequences
      for the families of DNA-binding proteins. The database contains 3238 full-length
      sequences (retrieved from the SWISS-PROT database, release 38) that include, at
      least, a DNA-binding domain. Sequence entries are organized into families defined
      by PROSITE patterns, PRINTS motifs and de novo excised signatures. Combining
      global similarities and functional motifs into a single classification scheme,
      DNA-binding proteins are classified into 33 unique classes, which helps to reveal
      comprehensive family relationships. To maximize family information retrieval,
      DnaProt contains a collection of multiple alignments for each DNA-binding family
      while the recognized motifs can be used as diagnostically functional
      fingerprints. All available structural class representatives have been
      referenced. The resource was developed as a Web-based management system for
      online free access of customized data sets. Entries are fully hyperlinked to
      facilitate easy retrieval of the original records from the source databases while
      functional and phylogenetic annotation will be applied to newly sequenced
      genomes. The database is freely available for online search of a library
      containing specific patterns of the identified DNA-binding protein classes and
      retrieval of individual entries from our WWW server
      (http://kronos.biol.uoa.gr/~mariak/dbDNA.html).

PMID- 11522920
TI  - Improved protein loop prediction from sequence alone.
AB  - The SLoop database of supersecondary fragments, first described by Donate et al.
      (Protein Sci., 1996, 5, 2600-2616), contains protein loops, classified according
      to structural similarity. The database has recently been updated and currently
      contains over 10 000 loops up to 20 residues in length, which cluster into over
      560 well populated classes. The database can be found at http://www
      cryst.bioc.cam.ac.uk/~sloop. In this paper, we identify conserved structural
      features such as main chain conformation and hydrogen bonding. Using the original
      approach of Rufino and co-workers (1997), the correct structural class is
      predicted with the highest SLoop score for 35% of loops. This rises to 65% by
      considering the three highest scoring class predictions and to 75% in the top
      five scoring class predictions. Inclusion of residues from the neighbouring
      secondary structures and use of substitution tables derived using a reduced
      definition of secondary structure increase these prediction accuracies to 58, 78
      and 85%, respectively. This suggests that capping residues can stabilize the loop
      conformation as well as that of the secondary structure. Further increases are
      achieved if only well-populated classes are considered in the prediction. These
      results correspond to an average loop root mean square deviation of between 0.4
      and 2.6 A for loops up to five residues in length.

PMID- 11522921
TI  - A fast method for predicting amino acid mutations that lead to unfolding.
AB  - Amino acid mutation(s) that cause(s) partial or total unfolding of a protein can
      lead to disease states and failure to produce mutants. It is therefore very
      useful to be able to predict which mutations can retain the conformation of a
      wild-type protein and which mutations will lead to local or global unfolding of
      the protein. We have developed a fast and reasonably accurate method based on a
      backbone-dependent side-chain rotamer library to predict the (folded or unfolded)
      conformation of a protein upon mutation. This method has been tested on proteins
      whose wild-type 3D structures are known and whose mutant conformations have been
      experimentally characterized to be folded or unfolded. Furthermore, for the cases
      studied here, the predicted partially folded or denatured mutant conformation
      correlate with a decrease in the stability of the mutant relative to the wild
      type protein. The key advantage of our method is that it is very fast and
      predicts locally or globally unfolded states fairly accurately. Hence, it may
      prove to be useful in designing site-directed mutagenesis, X-ray crystallography
      and drug design experiments as well as in free energy simulations by helping to
      ascertain whether a mutation will alter or retain the wild-type conformation.

PMID- 11522922
TI  - Protein minimization by random fragmentation and selection.
AB  - Protein-protein interactions are involved in most biological processes and are
      important targets for drug design. Over the past decade, there has been increased
      interest in the design of small molecules that mimic functional epitopes of
      protein inhibitors. BLIP is a 165 amino acid protein that is a potent inhibitor
      of TEM-1 beta-lactamase (K(i) = 0.1 nM). To aid in the development of new
      inhibitors of beta-lactamase, the gene encoding BLIP was randomly fragmented and
      DNA segments encoding peptides that retain the ability to bind TEM-1 beta
      lactamase were isolated using phage display. The selected peptides revealed a
      common, overlapping region that includes BLIP residues C30-D49. Synthesis and
      binding analysis of the C30-D49 peptide indicate that this peptide inhibits TEM-1
      beta-lactamase. Therefore, a peptide derivative of BLIP that has been reduced in
      size by 88% compared with wild-type BLIP retains the ability to bind and inhibit
      beta-lactamase.

PMID- 11522923
TI  - Design, production and characterization of FLIN2 and FLIN4: the engineering of
      intramolecular ldb1:LMO complexes.
AB  - The nuclear LIM-only (LMO) transcription factors LMO2 and LMO4 play important
      roles in both normal and leukemic T-cell development. LIM domains are
      cysteine/histidine-rich domains that contain two structural zinc ions and that
      function as protein-protein adaptors; members of the LMO family each contain two
      closely spaced LIM domains. These LMO proteins all bind with high affinity to the
      nuclear protein LIM domain binding protein 1 (ldb1). The LMO-ldb1 interaction is
      mediated through the N-terminal LIM domain (LIM1) of LMO proteins and a 38
      residue region towards the C-terminus of ldb1 [ldb1(LID)]. Unfortunately,
      recombinant forms of LMO2 and LMO4 have limited solubility and stability,
      effectively preventing structural analysis. Therefore, we have designed and
      constructed a fusion protein in which ldb1(LID) and LIM1 of LMO2 can form an
      intramolecular complex. The engineered protein, FLIN2 (fusion of the LIM
      interacting domain of ldb1 and the N-terminal LIM domain of LMO2) has been
      expressed and purified in milligram quantities. FLIN2 is monomeric, contains
      significant levels of secondary structure and yields a sharp and well-dispersed
      one-dimensional (1)H NMR spectrum. The analogous LMO4 protein, FLIN4, has almost
      identical properties. These data suggest that we will be able to obtain high
      resolution structural information about the LMO-ldb1 interactions.

PMID- 11522924
TI  - Thermostabilization by replacement of specific residues with lysine in a Bacillus
      alkaline cellulase: building a structural model and implications of newly formed
      double intrahelical salt bridges.
AB  - An alkaline, mesophilic endo-1,4-beta-glucanase from alkaliphilic Bacillus sp.
      strain KSM-64 was significantly thermostabilized by replacement of both Asn179
      and Asp194 with lysine by site-directed mutagenesis. Structural remodeling of the
      mutant enzyme newly generated by the double mutation suggested that Glu175-
      >Lys179 and Glu190-->Lys194 were the most plausible ion pairs, both of which
      involved side chains at the i and i + 4 positions on the alpha(4)-helix from
      Glu175 to Ser195. By molecular dynamics simulations, the N(zeta) hydrogens of
      Lys179 and Lys194 were found to coordinate with the carbonyl O(varepsilon1) and
      O(varepsilon2) of Glu175 and the carbonyl O(varepsilon1) of Glu190, respectively,
      with distances of around 2 A for all. These results confirm that the formation of
      these double intrahelical ion pairs (salt bridges) is responsible for the
      thermostabilization by the double mutation.

PMID- 11522925
TI  - The determinants of alpha-amylase pH-activity profiles.
AB  - The glycosyl hydrolases present a large family of enzymes that are of great
      significance for industry. Consequently, there is considerable interest in
      engineering the enzymes in this family for optimal performance under a range of
      very diverse conditions. Until recently, tailoring glycosyl hydrolases for
      specific industrial processes mainly involved stability engineering, but lately
      there has also been considerable interest in engineering their pH-activity
      profiles. We mutated four neutral residues (N190, F290, N326 and Q360) in the
      chimeric Bacillus Ba2 alpha-amylase to both charged and neutral amino acids. The
      results show that the pH-activity profile of the Ba2 alpha-amylase can be changed
      by inserting charged residues close to the active site. The changes in the pH
      activity profile for these neutral --> charged mutations do not, however,
      correlate with the predictions from calculations of the p K(a) values of the
      active site residues. More surprisingly, the neutral --> neutral mutations change
      the pH-activity profile as much as the neutral --> charged mutations. From these
      results, it is concluded that factors other than electrostatics, presumably the
      dynamic aspects of the active site, are important for the shape of the pH
      activity profiles of the alpha-amylases.

PMID- 11522926
TI  - Preparation and crystal structure of the recombinant alpha(1)/alpha(2) catalytic
      heterodimer of bovine brain platelet-activating factor acetylhydrolase Ib.
AB  - The intracellular form of mammalian platelet activating factor acetylhydrolase
      found in brain (PAF-AH Ib) is thought to play a critical role in control in
      neuronal migration during cortex development. This oligomeric complex consists of
      a homodimer of the 45 kDa (beta) LIS1 protein, the product of the causative gene
      for type I lissencephaly, and, depending on the developmental stage and species,
      one of three possible pairs of two homologous approximately 26 kDa alpha
      subunits, which harbor all of the catalytic activity. The exact composition of
      this complex depends on the expression patterns of the alpha(1) and alpha(2)
      genes, exhibiting tissue specificity and developmental control. All three
      possible dimers (alpha(1)/alpha(1), alpha(1)/alpha(2) and alpha(2)/alpha(2)) were
      identified in tissues. The alpha(1)/alpha(2) heterodimer is thought to play an
      important role in fetal brain. The structure of the alpha(1)/alpha(1) homodimer
      was solved earlier in our laboratory at 1.7 A. We report here the preparation of
      recombinant alpha(1)/alpha(2) heterodimers using a specially constructed bi
      cistronic expression vector. The approach may be useful in studies of other
      systems where pure heterodimers of recombinant proteins are required. The
      alpha(1)/alpha(2) dimer has been crystallized and its structure was solved at 2.1
      A resolution by molecular replacement. These results set the stage for a detailed
      characterization of the PAF-AH Ib complex.

PMID- 11522928
TI  - The end of Alzheimer disease II: commentary on "Decisions to treat or not to
      treat pneumonia in demented psychogeriatric nursing home patients".

PMID- 11522930
TI  - The association between caregiver burden and caregiver health-related quality of
      life in Alzheimer disease.
AB  - The burden experienced by family caregivers of individuals with Alzheimer disease
      (AD) affects the caregivers' overall health-related quality of life (HRQOL).
      Assessing the influence on HRQOL is an integral part of determining the efficacy
      and economic attractiveness of interventions for AD. Generic preference-weighted
      instruments such as the Health Utilities Index Mark 2 (HUI2) are recommended for
      measuring HRQOL for cost-effectiveness studies. However, these instruments focus
      on physical attributes and have not been tested in an AD caregiver population. We
      administered the HUI2 to a population of 679 caregivers to people with AD at 13
      community and institutional sites in the United States. We also administered the
      Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36), a caregiver time
      questionnaire, and a caregiver burden instrument. The mean global HUI2 utility
      score for caregivers was 0.87 and varied little by the affected person's setting
      of care and AD stage (range, 0.86-0.89; p > 0.2). The caregiver burden scales all
      varied by the affected person's setting of care, and some also varied by disease
      severity. The mental health component summary score of the SF-36 for caregivers
      varied across both disease stage and setting. Caregiver time increased for
      caregivers of AD-affected persons with more severe cognitive impairment. Generic
      preference-weighted instruments may not adequately capture differences in the
      burden of caregivers of those with AD. The development of condition-specific
      preference-weighted instruments may provide the means to better estimate HRQOL in
      AD caregivers.

PMID- 11522929
TI  - Decisions to treat or not to treat pneumonia in demented psychogeriatric nursing
      home patients: evaluation of a guideline.
AB  - We evaluated a new guideline, in the form of a "checklist of considerations," to
      support end-of-life decision making in the treatment of demented patients with
      pneumonia. Questionnaires were sent to nursing home physicians (NHPs) in The
      Netherlands at three times: before implementation of the checklist (concerning 91
      individual patients), during use of the checklist (concerning another 107
      individual patients), and after data collection (concerning the targeted patient
      category of demented nursing home patients with pneumonia as a whole). In the
      last questionnaire, one NHP from each nursing home (n = 55 NHPs) gave his or her
      general opinion about the checklist. We measured the usefulness of the checklist
      in supporting decision making and its frequency of actual use. The NHPs accepted
      the contents of the checklist for use in the targeted patient category. It was
      used in 46% of the incident cases of pneumonia. The checklist was considered more
      useful in supporting decision making for the targeted patient category (85% of
      the NHPs) than for the individual patient (47%). Possible explanations for this
      discrepancy in "usefulness" include the difference in the nature of the outcome
      measures and the fact that the checklist was used more frequently for the "easier
      cases." Information on individual patient level, patient category level, and
      nursing home and NHP characteristics is used to suggest checklist improvements.

PMID- 11522931
TI  - Caregivers' attitudes toward their family members' participation in Alzheimer
      disease research: implications for recruitment and retention.
AB  - Current levels of participation in Alzheimer disease (AD) research are
      inadequate, particularly among nonwhites. This study was conducted to examine
      caregivers' attitudes toward their family members' participation in AD research.
      Six focus group interviews were conducted with 38 white and 12 African-American
      caregivers of participants enrolled in clinical research projects. Both white and
      African-American families participated in research to help their care recipients
      and future generations, receive support from the clinical and research staff, and
      obtain feedback about patient status and research results. Among white
      caregivers, primary barriers to participation in research included the potential
      for no direct benefit, problems with the procedures and tests involved, lack of
      time and resources, and difficulty accepting the diagnosis. Among African
      American caregivers, primary barriers included general skepticism about the
      research process and firmly established attitudes about medical treatment and
      help seeking that serve as disincentives to research participation. To maximize
      the perceived benefits of research participation, potential participants should
      have access to regular personal contact with staff, information about health
      status changes in the care recipient, and the short-term and long-term results of
      the research studies in which they are participants. In addition, researchers
      should be sensitive to the concerns that may serve as barriers to participation,
      particularly among African Americans.

PMID- 11522932
TI  - Information and competency for consent to pharmacologic clinical trials in
      Alzheimer disease: an empirical analysis in patients and family caregivers.
AB  - This study was undertaken to evaluate (1) what information normal and Alzheimer
      disease (AD) participants are able to manage; (2) the correlation between the
      degree of competency and age, education and dementia scores, and the ability of
      dementia scores to predict incompetence; and (3) the capacity to retain consent
      related information. To fulfil these aims, a four-point competency rating scale
      (1 = incompetent, 2 = marginally competent, 3 = sufficiently competent, and 4 =
      completely competent) was used in 70 patients (Mini-Mental State Examination
      [MMSE] score >9; Global Deterioration Scale score <6) and in 40 cognitively
      normal caregivers. Patients were divided into two subgroups (competency ratings 1
      and 2 versus 3 and 4) to calculate positive and negative predictive values of
      MMSE and Alzheimer Disease Assessment Scale-cognitive (ADAScog) for
      absent/marginal competence. Main results were as follows: (1) 32.9% of AD
      patients were "incompetent" (no caregivers), 37.1% were "marginally competent"
      (20% caregivers), 18.6% were "sufficiently competent" (50% caregivers), and 11.4%
      were "completely competent" (30% caregiverss). (2) Competency ratings and age did
      not correlate in AD, whereas a negative correlation was significant in
      caregivers; competency ratings positively correlated to education in caregivers.
      (3) ADAScog and MMSE were the tests most significantly correlated to competency;
      MMSE score below 18 had a positive predictive value of 95% and a negative
      predictive value of 63.3%. The fact that 95% of patients with MMSE scores below
      18 are incompetent or marginally competent points to an urgent need for ethical
      procedures capable of creating a balance between difficulties in obtaining valid
      consent and a patient's right to benefit from advances in clinical research.

PMID- 11522933
TI  - Interobserver disagreements on clinical dementia rating assessment:
      interpretation and implications for training.
AB  - The Clinical Dementia Rating (CDR) is a widely used semiobjective instrument for
      staging dementia severity. A global CDR score is reported that is derived from
      individual scores in six domains. In this study, we examined both agreement and
      disagreement, among raters and with a gold standard, to identify domain-specific
      and global dementia severity level ratings that would most benefit from further
      training or greater emphasis in future training. We found that raters-in-training
      experienced the most difficulty with rating normal and questionable dementia.
      They also had the most trouble scoring the memory domain. When they disagreed
      with the gold standard, they nearly always gave higher ratings. A third,
      extremely experienced group of raters were uniform in their high levels of
      agreement on each domain and the global CDR and tended to give lower ratings if
      they disagreed with the gold standard. Analysis of the agreement and disagreement
      patterns suggested that greater emphasis on the memory, home and hobbies, and
      orientation domains during CDR training, and increasing the information provided
      for the judgment and problem solving domain on the standardized CDR worksheets,
      could improve the consistency of raters and increase the efficiency with which
      they are trained to use the CDR.

PMID- 11522934
TI  - An open-label, 24-week pilot study of the methyl donor betaine in Alzheimer
      disease patients.
AB  - We investigated the safety and tolerability of betaine in patients with Alzheimer
      disease (AD). Betaine is an alternative methyl donor, distinct from the folate
      and cobalamin-dependent conversion pathway between homocysteine and methionine.
      Betaine has been used successfully to reduce homocysteine levels in
      homocystinuria. The rationale for betaine in AD was to decrease serum
      homocysteine levels and to increase brain methionone and S-adenosylmethionine,
      both of which might delay disease progression. Hyperhomocysteinemia is a possible
      risk factor for AD. Eight patients with probable mild AD (7 men; mean age, 69.6
      years; mean Mini-Mental State Exam score, 23.7) received oral betaine (3 g twice
      daily) for 24 weeks. All patients were on donepezil 10 mg/day for at least 3
      months before entry and throughout the study. One patient suffered a myocardial
      infarction and withdrew after 6 weeks. Another patient, who completed the trial,
      experienced diarrhea and prostatitis. Four of the 7 patients who completed the
      trial were rated on the Clinician's Global Impression of Change as worse after 24
      weeks. On the cognitive portion of the AD Assessment Scale, 2 patients worsened
      by at least five points over 24 weeks, whereas the others had changes in scores
      of no more than two points either way. Six of 8 patients tolerated betaine for 24
      weeks without difficulty. Several patients worsened over 24 weeks, but as a pilot
      study without a control group, efficacy measurements cannot be interpreted. The
      current study provides a basis for pursuing larger controlled trials with betaine
      in AD. The homocysteine to S-adenosylmethionine pathway is of interest in AD
      therapeutics.

PMID- 11522936
TI  - Ca2+ signaling regulated by an ATP-dependent autocrine mechanism in astrocytes.
AB  - Although the mechanisms of Ca2+ wave propagation in astrocytes induced by
      mechanical stimulation have been well studied, it is still not known how the
      [Ca2+]i increases in the stimulated cells. Here, we have analyzed the mechanisms
      of [Ca2+]i increase in single, isolated astrocytes. Our results showed that there
      was an autocrine mechanism of Ca2+ regulation mediated by ATP in mechanically
      stimulated astrocytes. This autocrine mechanism induced the activation of
      phospholipase C via a G-protein, resulting in Ca2+ release from intracellular
      Ca2+ stores. A second pathway mediating a [Ca2+]i increase was via a Ca2+ influx
      from the extracellular space, which, interestingly, suppressed an intracellular
      Ca2+ oscillation. These two different Ca2+ cascades are involved in signal
      transduction and may function separately during intercellular communication.

PMID- 11522935
TI  - Group I mGluR antagonist AIDA protects nigral DA cells from MPTP-induced injury.
AB  - The effects of i.c.v. injection of AIDA, a group I mGluR antagonist, were studied
      on the nigral DA cells after MPTP-induced injury in the black mouse, using TH
      immunocytochemistry and unbiased stereology. MPTP reduced the total number of TH
      IR neurons by 55.2% and non-TH-IR neurons by 27.5%. A 15 min AIDA pre-treatment
      (10 nmol) selectively counteracted the loss of TH-IR cells caused by MPTP as
      evaluated 10 days after the insult without changing the total number of non
      neuronal cell nuclei. The results suggest that group I mGluR antagonists may have
      a neuroprotective role against MPTP-induced degeneration of DA neurons and thus
      probably also against neurodegenerative processes occurring in Parkinson's
      disease.

PMID- 11522937
TI  - Prostaglandin D2 synthase induces apoptosis in PC12 neuronal cells.
AB  - Apoptosis of neuronal cells is a proposed cause of certain neurological
      disorders. Here, we report on a 5- to 6-fold increase in apoptosis by exposure to
      prostaglandin D2 synthase (PGD2S) in PC12 neuronal cells. Apoptosis was detected
      by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end-labeling
      (TUNEL) assay, and appears to be mediated via caspase-3 activation.
      Neutralization with anti-PGD2S antibody or pre-treatment with selenium, which
      inhibits PGD2S enzymatic activity, both significantly inhibited the PGD2S-induced
      apoptosis, however, neither had any effect on the apoptosis induced by the known
      neuronal apoptotic inducer, glutamate. In addition, prostaglandins E1, E2, and
      F2alpha all inhibited the PGD2S-induced apoptosis while prostaglandin H2 had no
      significant effect. Furthermore, PGD2S isolated from human serum was more
      effective at inducing apoptosis then recombinantly expressed protein, presumably
      due to glycosylation. This novel role of PGD2S, as an inducer of apoptosis, may
      have implications in PC12 differentiation and possibly some neurological
      disorders.

PMID- 11522938
TI  - Huperzine A attenuates hydrogen peroxide-induced apoptosis by regulating
      expression of apoptosis-related genes in rat PC12 cells.
AB  - The present studies investigated effects of huperzine A (HupA), a selective
      acetylcholinesterase (AChE) inhibitor and promising anti-dementia agent, on
      hydrogen peroxide (H2O2)-induced apoptosis and the expression of apoptosis
      related genes in rat pheochromocytoma line PC12 cells. Transient exposure of the
      cells to H2O2 (100 microM) triggered a typical apoptosis as evidenced by
      chromatin condensation, nuclei fragmentation and DNA laddering. RT-PCR studies
      showed up-regulated p53 and Bax but lowered Bcl-2 mRNA levels with H2O2
      treatment. The results were further confirmed at protein levels by
      immunocytochemistry with specific antibodies. Preincubation with HupA (1 microM)
      significantly prevented the cells from apoptosis, attenuated H2O2-induced over
      expression of Bax and p53, and rehabilitated the level of Bcl-2. The present
      findings suggest that HupA exerts significant protection against H2O2-induced
      apoptosis, possibly through improving expression of apoptosis-related genes.

PMID- 11522939
TI  - NT-3 regulates BDNF-induced modulation of synaptic transmission in cultured
      hippocampal neurons.
AB  - BDNF and NT-3 can modulate the development and plasticity of central synaptic
      transmission. Although the expression of NT-3 and BDNF in the rodent hippocampus
      coincides during perinatal development, little is known about possible functional
      interactions between both neurotrophins in synaptic development. Here, we have
      investigated the effects of combined long-term application of NT-3 and BDNF on
      excitatory glutamatergic (mEPSC) and inhibitory GABAergic miniature synaptic
      currents (mIPSC) in cultured embryonic hippocampal neurons. Our results show that
      the BDNF-induced twofold increase in mEPSC frequency is abolished by pre
      treatment with NT-3. In addition, the NT-3-induced twofold downregulation of
      mIPSC frequency is reversed by BDNF. Finally, the BDNF-induced increase in c-fos
      expression is reduced by 50% after pre-treatment with NT-3. In summary, these
      data suggest an NT-3 controlled modulation of BDNF signalling in differentiating
      hippocampal neurons.

PMID- 11522940
TI  - Enhanced expression of I-kappaB with neurofibrillary pathology in Alzheimer's
      disease.
AB  - Inflammatory and immune responses are known to be involved in the pathogenesis of
      Alzheimer's disease (AD). NF-kappaB is a major transcription factor that plays a
      central role in the inflammatory and immune responses and is regulated by I
      kappaB through an autoregulatory feedback system. Southwestern
      immunohistochemistry and immunohistochemistry in our study demonstrated activated
      NF-kappaB in AD brains. However, there was also activated expression of I-kappaB
      in a distribution that corresponded to the neurofibrillary pathology of AD. These
      observations indicate that disruption of the autoregulatory mechanism of NF
      kappaB in brain regions with neurofibrillary pathology may play a role in the
      pathogenesis of AD.

PMID- 11522942
TI  - Processing specificity for human voice stimuli: electrophysiological evidence.
AB  - Recent neuroimaging studies have provided evidence for localized perceptual
      specificity in the processing of human voice stimuli, paralleling the specificity
      for human faces. This study attempted to delineate the perceptual features of
      human voices yielding selective processing, and to characterize its time-course.
      Electrophysiological recordings revealed a positive potential peaking at 320 ms
      post-stimulus onset, in response to sung tones compared with fundamental
      frequency-matched instrumental tones, when both categories were distracters in an
      oddball task. This voice-specific response (VSR) evoked under conditions
      different from those yielding positivity at that latency in other contexts,
      indicates the overriding salience of voice stimuli, possibly reflecting the
      operation of a gating system directing voice stimuli to be processed differently
      from other acoustic stimuli.

PMID- 11522941
TI  - Reduced IP3 sensitivity of IP3 receptor in Purkinje neurons.
AB  - The inositol 1,4,5-trisphosphate receptor (IP3R) is highly expressed in Purkinje
      neurons (PNs) and is thought to be essential for the induction of long-term
      depression at parallel-fiber-PN synapses. Here, by imaging the fluorescence
      intensity of the low-affinity Ca2+ indicator inside the Ca2+ stores in the
      permeabilized single PNs, we analyzed the kinetics of Ca2+ release via the IP3R
      in controlled cytoplasmic environments. The rate of Ca2+ release is dependent on
      the IP3 concentration with an EC50 of 25.8 microM, which is > 20-fold greater
      than that of the IP3R in the isolated preparations or in peripheral cells. This
      property would be advantageous in inducing the release of Ca2+ in a localized
      space adjacent to the site of synaptic inputs.

PMID- 11522943
TI  - Effect of menopause on cognitive performance in women with Down syndrome.
AB  - We compared cognitive function in nondemented pre- and postmenopausal women with
      Down syndrome, aged 21-57 years, with their age-matched male peers. The Woodcock
      Johnson Tests of Cognitive Ability-Revised were used to assess cognitive function
      at baseline and 2 years later. Premenopausal women performed better than their
      age-matched male peers, while postmenopausal women performed more poorly than age
      matched male peers (p = 0.007). Premenopausal women and young men showed no
      significant declines in cognition over time. Postmenopausal women, but not their
      age-matched male peers, showed significant declines in cognitive function. Our
      results support the hypothesis that cognitive declines in postmenopausal women
      are associated with estrogen deficiency rather than with age.

PMID- 11522944
TI  - Immunosuppressant FK506 does not exert beneficial effects in symptomatic G93A
      superoxide dismutase-1 transgenic mice.
AB  - The immunosuppressant drug FK506 has been shown to exert neuroprotective effects
      in various model systems via inhibition of the protein phosphatase calcineurin
      (CN). The enzyme Cu/Zn-superoxide dismutase (SOD1), which is mutated in a
      familial form of amyotrophic lateral sclerosis (ALS), is an endogenous regulator
      of CN. Altered function of CN may therefore be involved in the pathogenesis of
      ALS. We tested FK506 in a transgenic mouse model expressing mutated SOD1 for
      potential beneficial effects. This treatment, initiated after onset of symptoms,
      did not cause a reduction in the decline of motor function nor did it prolong
      survival. These results argue against a crucial role of CN in the process leading
      to motoneuronal degeneration in SOD1-mutated mice.

PMID- 11522945
TI  - NO donor SIN-1 potentiates monosynaptic reflexes in the cat spinal cord.
AB  - The effect produced by the nitric oxide donor SIN-1 on monosynaptic reflexes was
      examined. Experiments were performed on anesthetized, paralyzed and spinalized
      cats. Lumbar monosynaptic reflexes were produced by stimulation of Ia afferents.
      I.v. application of SIN-1 (500 microg/kg) produced a mean marked potentiation of
      704% of pre-drug control (100%) in the amplitude of monosynaptic reflexes. In
      addition, in other experiments a concentration-dependent effect on the amplitude
      of monosynaptic reflexes was observed after microinjections of SIN-1 into the
      ventral horn (1 microl; 10(-12) - 10(-3) M), with a mean facilitatory effect of
      355%. In both cases, the potentiation was reversible 45 min after i.v. or local
      application of SIN-1. These results provide the first evidence that monosynaptic
      reflexes can be potentiated by nitric oxide.

PMID- 11522946
TI  - BDNF induces glutamate release in cerebrocortical nerve terminals and in cortical
      astrocytes.
AB  - In this paper we report that BDNF is able to stimulate the release of glutamate
      not only in cerebrocortical nerve terminals, but also in cortical astrocytes. The
      process of glutamate release, in both nerve terminals and astrocytes, is
      dependent upon the extracellular and intracellular Ca2+ levels and involves
      exocytosis, since tetanus toxin treatment abolishes the release of glutamate from
      both preparations. Further, preincubation of nerve terminals or astrocytes with
      K252a (a tyrosine kinase inhibitor) inhibits BDNF-evoked glutamate release,
      suggesting the involvement of Trk B receptors in this process. In astrocytes, the
      level of BDNF-induced glutamate release is higher in immature than in more mature
      cells. The results suggest a new pathway of cross-talk between neurons and
      astrocytes, which may play a role in synaptic plasticity and neurotoxicity.

PMID- 11522947
TI  - Ca2+ -dependent activation of tyrosine hydroxylase involves MEK1.
AB  - Tyrosine hydroxylase (TOH) activity is regulated acutely by phosphorylation of
      serines 8, 19, 31 and 40. The only kinases known to phosphorylate Ser31 are the
      mitogen-activated protein kinases MAPK-1 and 2. The involvement of these kinases
      in TOH activation in situ was therefore investigated using intact bovine
      chromaffin cells. Nicotine, K+ and A23187 increased TOH activity over 10 min in a
      Ca2+-dependent manner. The response to all three was reduced by PD098059, a
      selective inhibitor of the upstream activator of MAPK, MEK1. In contrast, TOH
      activation by forskolin and phorbol dibutyrate were unaffected by PD098059. The
      results support a key role for MEK1/MAPK in the acute activation of TOH by
      nicotinic receptors and by other agonists that increase cytosolic Ca2+.

PMID- 11522948
TI  - Functional regeneration of a gravity sensory system during development in an
      insect (Gryllus bimaculatus).
AB  - The efficiency of the regenerated cercal gravity sensory system was investigated
      in adult crickets (Gryllus bimaculatus). Regeneration was induced by amputations
      of cerci during different periods of development. Numbers of gravity-sensitive
      (clavate) sensilla on regenerated and intact cerci were identical if amputations
      were performed up to four times before the 6th instar. If older instars were
      included, regenerated cerci had fewer clavate sensilla than intact cerci.
      Compensatory head responses induced by stimulation of either regenerated or
      intact gravity sense organs were identical if cerci were amputated up to three
      times. However, four or more amputations caused weaker responses in the
      regenerated than in the intact sense organs. These experiments make the existence
      of a sensitive period during development of the cercal gravity sensory system
      unlikely. They support the postulation that functional regeneration is influenced
      by neuroplastic processes and proprioceptive gravity sensitive systems.

PMID- 11522949
TI  - In vivo hydroxyl radical formation after quinolinic acid infusion into rat corpus
      striatum.
AB  - We studied the effect of an acute infusion of quinolinic acid (QUIN) on in vivo
      hydroxyl radical (.OH) formation in the striatum of awake rats. Using the
      microdialysis technique, the generation of.OH was assessed through
      electrochemical detection of the salicylate hydroxylation product 2,3
      dihydroxybenzoic acid (2,3-DHBA). The .OH extracellular levels increased up to 30
      times over basal levels after QUIN infusion (240 nmol/microl), returning to the
      baseline 2 h later. This response was attenuated, but not abolished, by
      pretreatment with the NMDA receptor antagonist MK-801 (10 mg/kg, i.p.) 60 min
      before QUIN infusion. The mitochondrial toxin 3-nitropropionic acid (3-NPA, 500
      nmol/microl) had stronger effects than QUIN on .OH generation, as well as on
      other markers of oxidative stress explored as potential consequences of .OH
      increased levels. These results support the hypothesis that early .OH generation
      contributes to the pattern of toxicity elicited by QUIN. The partial protection
      by MK-801 suggests that QUIN neurotoxicity is not completely explained through
      NMDA receptor overactivation, but it may also involve intrinsic QUIN oxidative
      properties.

PMID- 11522950
TI  - Disordered visual processing and oscillatory brain activity in autism and
      Williams syndrome.
AB  - Two developmental disorders, autism and Williams syndrome, are both commonly
      described as having difficulties in integrating perceptual features, i.e. binding
      spatially separate elements into a whole. It is already known that healthy adults
      and infants display electroencephalographic (EEG) gamma-band bursts (around 40
      Hz) when the brain is required to achieve such binding. Here we explore gamma
      band EEG in autism and Williams Syndrome and demonstrate differential
      abnormalities in the two phenotypes. We show that despite putative processing
      similarities at the cognitive level, binding in Williams syndrome and autism can
      be dissociated at the neurophysiological level by different abnormalities in
      underlying brain oscillatory activity. Our study is the first to identify that
      binding-related gamma EEG can be disordered in humans.

PMID- 11522951
TI  - Hyperpolarization-activated (Ih) current in mouse vestibular primary neurons.
AB  - The presence of a hyperpolarization-activated inward current (Ih) was
      investigated in mouse vestibular primary neurons using the whole-cell patch-clamp
      technique. In current-clamp configuration, injection of hyperpolarizing currents
      induced variations of membrane voltage with prominent time-dependent
      rectification increasing with current amplitudes. This effect was abolished by 2
      mM Cs+ or 100 microM ZD7288. In voltage-clamp configuration, hyperpolarization
      pulses from -60 mV to -140 mV triggered a slow activating and non inactivating
      inward current that was sensitive to the two blockers, but insensitive to 5 mM
      Ba2+. Changing Na+ and K+ concentrations demonstrated that Ih current is carried
      by both these monovalent cations. This is the first demonstration of a Ih current
      in vestibular primary neurons.

PMID- 11522952
TI  - Profile of phosphoprotein labelling in organotypic slice cultures of rat
      hippocampus.
AB  - In recent years organotypic slice cultures of hippocampal tissue of rats have
      been widely used to study factors involved in neuronal death. Here we used 2D
      electrophoresis to study the phosphoprotein profile in such cultures and the
      effect of oxygen/glucose deprivation on this profile. Cultures were prepared from
      7-day-old rats. After 14 days in culture the phosphorylation profile in the
      cultures, as shown by phospho-protein markers undergoing developmental change,
      closely resembled the profile of fresh tissue from 23-day-old rats. The results
      suggest that this model could be a good method to observe the development of the
      tissue and its response to an ischaemic lesion

PMID- 11522953
TI  - Alternative splicing of mGlu6 gene generates a truncated glutamate receptor in
      rat retina.
AB  - A novel splice variant of metabotropic glutamate receptor type 6 (mGlu6 receptor)
      was identified by reverse transcription-polymerase chain reaction amplification
      and sequence analysis of rat retina cDNA. The new rat receptor isoform (mGlu6b
      receptor) is characterized by an additional exon of 88 nucleotides containing an
      inframe stop codon, thus predicting the expression of a truncated protein of 508
      amino acids. In situ hybridization reveals mGlu6b receptor mRNA to be
      predominantly expressed in the outer part of the inner nuclear layer of rat
      retina, containing ON-bipolar cells. The mGlu6b protein would comprise the
      extracellular domain of the receptor containing the ligand-binding site, but
      would lack the transmembrane and intracellular portions, thus possibly acting as
      a retinal soluble receptor for glutamate.

PMID- 11522954
TI  - Strain differences in freezing behavior of PVG hooded and Sprague-Dawley rats:
      differential cortical expression of cholecystokinin2 receptors.
AB  - PVG hooded, but not Sprague-Dawley (SD), rats showed remarkable freezing behavior
      on cat exposure. Experiments using cDNA microarray and reverse transcriptase
      polymerase chain reaction (RT-PCR) demonstrated that cholecystokinin (CCK)2
      receptors were expressed to a greater extent in the PVG hooded rats. A CCK2
      antagonist, LY225910, inhibited freezing behavior in the PVG hooded rats while a
      CCK2 agonist, CCK-4, increased freezing behavior in the SD rats. These results
      strongly suggest that CCK2 receptors mediate the freezing behavior and the
      differential expression of these receptors underlie the strain difference in such
      behavior.

PMID- 11522955
TI  - Damage to the parietal lobe impairs bimanual coordination.
AB  - Moving the upper limbs at a common tempo according to a mirror or parallel mode
      represents elementary coordination dynamics. Previously, the role of the medial
      wall areas have been emphasized for successful production of these bimanual
      patterns. The involvement of the parietal lobe is less clear despite its
      importance for the representation of motor skill and sensorimotor integration.
      The objective of this study was to investigate temporal control in patients with
      parietal pathology when performing isofrequency configurations. As compared to
      control subjects, these patients showed desynchronization of movement
      trajectories that was most apparent during parallel patterns. These observations
      suggest the significant role of the parietal lobe for bimanual coordination which
      becomes increasingly relevant as a function of task complexity.

PMID- 11522956
TI  - Damage to nuclear DNA in Lewy body disease.
AB  - To assess the significance of damaged nuclear DNA in autopsy brain tissue in Lewy
      body disease (LBD), we examined the patterns of expression of two DNA repair
      enzymes (PARP and DNA-PKCS), TUNEL and caspase-3 activation, in sections of
      midbrain and frontal cortex from nine patients with LBD who had not received L
      DOPA, and from five neurologically normal controls. In LBD but not controls, many
      neurons and glia in the midbrain had translocated DNA-PKCS and PARP from the
      cytoplasm into the nucleus, particularly in the substantia nigra. LBD midbrains
      contained sparse TUNEL-positive neurons. Caspase-3 activity was largely
      restricted to microglia but was detected in an occasional nigral neuron. Nuclear
      DNA damage occurs in vivo in LBD but only rarely indicates neuronal apoptosis.

PMID- 11522957
TI  - NMDA receptors mediate hypoxic spine loss in cultured neurons.
AB  - We examined the pharmacology of dendritic morphologic changes in cultured
      cortical neurons exposed to sublethal oxygen-glucose deprivation (OGD). Confocal
      analysis of DiI-labeled neurons demonstrated transient dendritic swelling and
      spine loss after OGD. These morphological changes were reproduced by direct
      application of NMDA, kainate, veratridine, ionomycyin, and gramicidin, but not
      KCl. Blockade of voltage-gated sodium or calcium channels did not prevent OGD
      induced dendritic spine loss. In contrast, the NMDA receptor antagonist, MK-801,
      fully prevented these changes. An AMPA/kainate receptor antagonist, NBQX, had no
      effect by itself but reduced spine loss when added to MK-801. While alterations
      in dendrite morphology may be triggered by activation of disparate ion channels,
      rapid spine loss in hypoxic cortical neurons is mediated preferentially through
      activation of the NMDA subtype glutamate receptor.

PMID- 11522959
TI  - Proprioceptive input overrides vestibulo-spinal drive during human locomotion.
AB  - The aim of this study was to evaluate the influence of vestibulo-spinal drive on
      the performance of various locomotor-like movements. The extent of body rotation
      was assessed during walking (1 Hz and 2 Hz), running and hopping in place after
      vestibular stimulation (10 body rotations; 0.5 Hz). Compared to the controls,
      body rotations with eyes closed were larger during hopping than while running and
      smallest during walking independent of stepping frequency. A close correlation
      existed between the absolute duration of stance phase of the two legs and the
      rotation of the body. It is suggested that the amount of proprioceptive feedback
      from the legs determines the influence of vestibulo-spinal input on body
      movement.

PMID- 11522958
TI  - Altered dopaminergic transmission in the anorexic anx/anx mouse striatum.
AB  - We demonstrate abnormal dopaminergic neurotransmission in anorexic mice,
      homozygous for a recessive mutation (anx) causing starvation and motor
      disturbances. Isolated neurons from anx/anx striatum displayed a markedly
      increased activity of the Na+,K+-ATPase compared with normal littermates.
      Dopamine down-regulates Na+,K+-ATPase activity in striatal medium spiny neurons
      in rat, mouse and guinea pig. However, addition of dopamine in vitro failed to
      suppress the increased activity in anx/anx striatal neurons. Striatal dopamine
      and its metabolites, but not norepinephrine, were slightly but significantly
      lower in anx/anx mice than in normal littermates. We suggest that abnormal
      dopaminergic transmission may contribute to the anx phenotype.

PMID- 11522960
TI  - Expression of the kallikrein gene family in normal and Alzheimer's disease brain.
AB  - The human kallikrein gene family consists of 15 serine proteases. We examined the
      expression of the kallikrein genes in human cerebral cortex and hippocampus by RT
      PCR and compared their expression between Alzheimer's disease (AD) and control
      tissue. KLK1, 4, 5, 6, 7, 8, 10, 11, 13 and 14 are expressed in both cerebral
      cortex and hippocampus. KLK9 is expressed in cortex but not hippocampus, whereas
      KLK2, 3, 12 and 15 are not expressed in either tissue. We demonstrate an 11.5
      fold increase in KLK8 mRNA levels in AD hippocampus compared to controls. The
      KLK8 gene product, neuropsin, processes extracellular matrix and is important for
      neuronal plasticity. Therefore, the increase in KLK8 could have detrimental
      effects on hippocampal function in AD.

PMID- 11522961
TI  - Simultaneity of responses in a hierarchical visual network.
AB  - The pattern of anatomical connections between areas of the primate visual system
      is organized hierarchically. However, onset latencies in parietal and occipital
      stations are often simultaneous, and this seems to contradict hierarchical
      organization in its simplest interpretation, as serial organization. To
      understand the reasons for this contradiction, we simulated the cortical network
      for which there is onset data, including the network's hierarchical structure.
      The network's dynamics reproduced the simultaneous onset latencies reported in
      several dorsal areas. These results show that a strictly hierarchical visual
      system is compatible with much more complex dynamics than serial processing, and
      that hodological and biophysical properties, are more closely related to onset
      dynamics than is hierarchical organisation.

PMID- 11522962
TI  - Immunolocalization of voltage-gated potassium channel Kv3.1b subunit in the
      cochlea.
AB  - Immunohistochemical localization of voltage-gated potassium channel Kv3.1b
      subunit was studied in the cochlea. Intense Kv3.1b-like immunoreactivity was
      present in the type I, type III, type IV and suprastrial fibrocytes of the
      cochlear lateral wall. Immunostaining was also found in the interdental cells and
      the fibrocytes of the spiral limbus and in the supralimbal dark cells. K+ ions,
      which play a pivotal role in the mechanosensory transduction process in the inner
      ear, are recycled via gap junctional networks in the cochlea. These results
      suggest that the voltage-gated potassium channel, containing Kv3.1b, in the
      cochlear lateral wall fibrocytes may control the intracellular potential and play
      an important role in regulating the potassium ion recycling mechanism via gap
      junctions in the inner ear.

PMID- 11522963
TI  - Cajal-Retzius cell density as marker of type of focal cortical dysplasia.
AB  - Cajal-Retzius cells, identified using calretinin antiserum, were studied in layer
      I (LI) of adult human temporal cortex from epileptic patients with Taylor's focal
      cortical dysplasia and architectural dysplasia, in comparison with normal cortex.
      Both types of dysplasia showed LI hypercellularity, but only in architectural
      dysplasia was the density of Cajal-Retzius cells significantly increased. A
      subset of Cajal-Retzius cells were reelin immunoreactive, but none were GABA
      positive. These findings suggest that differences in the persistence of Cajal
      Retzius cells, which probably reflect different types of alteration during brain
      development, can assist in characterizing different forms of cortical dysplasia.

PMID- 11522964
TI  - Differential activation in parahippocampal and prefrontal cortex during word and
      face encoding tasks.
AB  - Episodic encoding is the first step in the formation of a memory trace. The
      relation between type of stimulus material and regional brain activation is not
      fully understood. We measured brain activation using fMRI in 12 healthy subjects
      during two experiments, word and face encoding. A widespread network of common
      activations in both tasks was present in the bilateral frontal (BA44/45),
      occipital (BA17/18/19) and fusiform gyri (BA37) as well as the right hippocampal
      formation (BA30). A region-of-interest-analysis for the hippocampal formation and
      dorsolateral prefrontal cortex (DLPFC) was performed additionally. During face
      encoding the right dorsal and during word encoding the bilateral ventral
      hippocampal region was activated. In the prefrontal cortex a lateralization to
      the left side was present only for word encoding. During encoding, activation in
      the inferior frontal and hippocampal cortex is modulated by the type of stimulus
      material.

PMID- 11522965
TI  - Amygdala response to both positively and negatively valenced stimuli.
AB  - Human lesion and functional imaging data suggest a central role for the amygdala
      in the processing of negative stimuli. To determine whether the amygdala's role
      in affective processing extends beyond negative stimuli, subjects viewed pictures
      that varied in emotional content (positive vs negative valence) and arousal level
      (high vs low) while undergoing functional magnetic resonance imaging. Amygdala
      activation, relative to a low arousal and neutral valence picture baseline, was
      significantly increased for both positively and negatively valenced stimuli and
      did not differ for the two valences. There were no laterality effects. Whereas
      arousal level appeared to modulate the amygdala response for negative stimuli,
      all positively valenced pictures (both high and low in arousal) produced
      significant amygdala responses. These results clearly demonstrate a role for the
      amygdala in processing emotional stimuli that extends beyond negative and fearful
      stimuli.

PMID- 11522966
TI  - What the brain needs for managing both hands at the same time.

PMID- 11522967
TI  - Methylene blue chromoendoscopy for detection of short-segment Barrett's
      esophagus.
AB  - BACKGROUND: The yield of intestinal metaplasia (IM) with randomly obtained biopsy
      specimens in patients with short lengths of columnar-appearing mucosa in the
      distal esophagus is low (30%-50%). Vital staining would be beneficial if it
      identified more patients with short-segment Barrett's esophagus (SSBE). Our aim
      was to compare the confirmation of IM in patients with suspected SSBE (columnar
      appearing mucosa <3 cm in length) by using methylene blue (MB)-directed versus
      random biopsies. METHODS: Consecutive patients undergoing EGD in whom columnar
      appearing mucosa less than 3 cm in length was visualized underwent MB staining.
      Stained areas within suspected SSBE segments were targeted for biopsies. All
      biopsy specimens were stained with H & E with alcian blue at pH 2.5 and evaluated
      by a single pathologist. A historical control group (different from patients
      undergoing MB staining) consisted of patients with less than 3 cm of columnar
      appearing mucosa in whom biopsy specimens were obtained randomly without MB
      staining. RESULTS: The MB group included 75 patients (mean age 63.8 +/- 10.9
      years) with a mean length of columnar-appearing mucosa of 1.2 cm (range 0.5-2.5
      cm). The control group included 83 patients (mean age 60.5 +/- 12.9 years) with a
      mean length of columnar-appearing mucosa of 1.16 cm (range 0.5-2.5 cm). IM (i.e.,
      confirmed SSBE) was detected in 61% of the MB group versus 42% of the control
      group (p = 0.0237). Patients in the MB group required significantly fewer
      biopsies (4.3 +/- 1.5 vs. 5.1 +/- 12.3, p = 0.0162). Confirmation of IM by length
      was as follows: less than 1 cm (irregular Z line), MB 17.4% versus control 25% (p
      = 0.73); 1 to less than 2 cm, MB 77% versus control 45% (p = 0.03); 2 to less
      than 3 cm, MB 90% versus control 58% (p = 0.02). CONCLUSIONS: MB chromoendoscopy
      significantly increases the detection of IM and requires fewer biopsies in
      patients with suspected SSBE with greater than 1 cm of columnar-appearing mucosa.
      It does not appear to be beneficial in patients with irregular Z lines (<1 cm).

PMID- 11522968
TI  - Comparison of methylene blue-directed biopsies and conventional biopsies in the
      detection of intestinal metaplasia and dysplasia in Barrett's esophagus: a
      preliminary study.
AB  - BACKGROUND: The diagnostic advantage of methylene blue (MB) chromoendoscopy in
      Barrett's esophagus is unclear. METHODS: Patients with columnar-lined esophagus
      (CLE) were enrolled into a prospective, randomized crossover trial of MB-directed
      biopsy versus conventional biopsy. RESULTS: Forty-seven patients (19 long-segment
      CLE; 28 short-segment CLE) were enrolled and underwent MB-directed biopsy.
      Sensitivity and specificity of MB for specialized intestinal metaplasia were 53%
      and 51%, respectively. Sensitivity and specificity of MB for dysplasia were 51%
      and 48%, respectively. Thirty-five patients (15 long-segment CLE; 20 short
      segment CLE) completed the crossover trial. Relative frequencies for specialized
      intestinal metaplasia were 73% and 71% from MB-directed and conventional biopsy
      specimens, respectively (p = 0.73). Relative frequencies for dysplasia were 20%
      and 18% from MB-directed and conventional biopsy specimens, respectively (p =
      0.65). In patients with long-segment CLE, dysplasia was diagnosed in 10 patients
      with MB and 7 patients with conventional biopsy methods (p = 0.25). The number of
      biopsy specimens per EGD was greater with MB, which may have influenced the
      diagnosis. Histologically, the grade of dysplasia was indefinite/low in nearly
      all of the dysplastic specimens. CONCLUSIONS: Results of MB-directed biopsy were
      similar to conventional biopsy in detecting specialized intestinal metaplasia and
      indefinite/low-grade dysplasia. MB was not useful in short-segment Barrett's
      esophagus.

PMID- 11522969
TI  - Complications of diagnostic and therapeutic colonoscopy within a defined
      population in Sweden.
AB  - BACKGROUND: Colonoscopy, introduced in the late 1960s, has become the principal
      method for diagnosis, treatment, and follow-up of colorectal diseases. Being
      invasive, colonoscopy is associated with a risk of complications. The aim of this
      study was to analyze the rate of complications of diagnostic and therapeutic
      colonoscopy in a population-based setting. METHODS: All colonoscopy records for
      1979 to 1995 in 1 Swedish county (population 258,000) were retrieved. Information
      was obtained about patients' demographics, date of examination, endoscopist,
      indications, findings, colonoscopy type, completion level, and complications.
      Records were linked to the Cause of Death Register and the Swedish Hospital
      Discharge Register to ascertain mortality and morbidity. RESULTS: In 6066
      colonoscopies, the overall morbidity was 0.4% (diagnostic 0.2%, therapeutic
      1.2%). The most frequent complications were bleeding (0.2%) and perforation
      (0.1%), with no colonoscopy-related mortality. Bleeding was confined to
      therapeutic colonoscopy and occurred immediately, mainly after removal of large
      polyps with thick stalks. Perforations at diagnostic colonoscopy occurred in the
      left colon; they were diagnosed sooner than perforations associated with
      therapeutic colonoscopy where the cecum was the most frequent site. The bleeding
      rate was correlated to the experience of the endoscopists. CONCLUSIONS:
      Colonoscopy is a safe procedure, and the rate of adverse events in this
      population-based setting was low.

PMID- 11522970
TI  - Patient experience and preferences toward colon cancer screening: a comparison of
      virtual colonoscopy and conventional colonoscopy.
AB  - BACKGROUND: Virtual colonoscopy has excellent sensitivity for the detection of
      cancer and polyps greater than 1 cm in diameter. For virtual colonoscopy to
      succeed as a screening test for colorectal neoplasia, it must be well tolerated
      and accepted by patients. Patients' experiences with virtual colonoscopy and
      conventional colonoscopy were assessed and compared. METHODS: Patients referred
      to the GI clinic for colonoscopy for any indication were recruited to undergo
      virtual colonoscopy before conventional colonoscopy. Patients were asked to
      complete a questionnaire twice: after virtual colonoscopy and after completing
      both tests. Three variables, overall pain, discomfort, and lack of respect, were
      assessed by using a 7-point Liken scale with higher scores denoting a worse
      experience. Patients' preferences for virtual colonoscopy versus conventional
      colonoscopy were determined with a time tradeoff technique. To verify response
      stability, patients were asked to return an additional questionnaire by mail at
      24 hours. RESULTS: Two hundred ninety-five patients completed the questionnaire
      immediately after the procedures, and 83 patients completed the questionnaire at
      24 hours. At both 0 and 24 hours, patients reported more pain, discomfort, and
      less respect after virtual colonoscopy than conventional colonoscopy (p < 0.01).
      The overall agreement (Kappa statistic) between times 0 and 24 hours was fair.
      Patients reported that they preferred conventional colonoscopy and would wait
      longer for conventional colonoscopy (mean = 4.9 weeks) than undergo a virtual
      colonoscopy (p < 0.01). CONCLUSIONS: Patients tolerate both virtual colonoscopy
      and conventional colonoscopy, although they report more pain, discomfort, and
      less respect undergoing virtual colonoscopy. Efforts to improve patient
      experience during virtual colonoscopy need to be investigated.

PMID- 11522971
TI  - A prospective study of EUS-guided celiac plexus neurolysis for pancreatic cancer
      pain.
AB  - BACKGROUND: Celiac plexus neurolysis, a chemical splanchnicectomy of the celiac
      plexus, is used to treat pain caused by pancreatic cancer. Most commonly, celiac
      plexus neurolysis is performed percutaneously under CT or fluoroscopic guidance,
      but can also be performed with EUS. The aim of this study was to prospectively
      assess the efficacy of EUS celiac plexus neurolysis in the management of pain
      caused by pancreatic cancer. METHODS: In this prospective study conducted in a
      community-based referral hospital, 58 patients with painful and inoperable
      pancreatic cancer were evaluated at 8 observation points before and after EUS
      celiac plexus neurolysis for up to 6 months. The following data were collected:
      age, gender, tumor location, vascular invasion, adjuvant therapy, and laboratory
      tests including prothrombin time, and complete blood counts were obtained at
      baseline (before EUS celiac plexus neurolysis); pain scores, morphine use, and
      adjuvant therapy were assessed at each observation. RESULTS: Pain scores were
      lower (p = 0.0001) 2 weeks after EUS celiac plexus neurolysis, an effect that was
      sustained for 24 weeks when adjusted for morphine use and adjuvant therapy. Forty
      five of the 58 patients (78%) experienced a decline in pain scores after EUS
      celiac plexus neurolysis. Chemotherapy with and without radiation also decreased
      pain after EUS celiac plexus neurolysis (p = 0.002). Procedure-related transient
      abdominal pain was noted in 5 patients; there were no major complications.
      CONCLUSIONS: EUS celiac plexus neurolysis is safe and controls pain caused by
      unresectable pancreatic cancer.

PMID- 11522972
TI  - Detection of choledocholithiasis by EUS in acute pancreatitis: a prospective
      evaluation in 100 consecutive patients.
AB  - BACKGROUND: ERCP is the standard for detection of choledocholithiasis in patients
      with acute biliary pancreatitis, and, if performed early, ERCP decreases
      morbidity. However, there are procedure-related complications. The aim of the
      present prospective study was to evaluate the ability of EUS to detect
      choledocholithiasis in patients presenting with acute pancreatitis. METHODS: The
      study group comprised 100 consecutive patients who presented with acute
      pancreatitis. EUS, and immediately thereafter, ERCP were performed by separate
      blinded examiners within 24 hours of admission. The diagnostic accuracy of EUS in
      identifying gallbladder stones was compared with that of transcutaneous US. The
      diagnostic accuracy of EUS in detecting choledocholithiasis was then compared
      with that of US and ERCP based on the results of endoscopic instrumentation of
      the bile duct after sphincterotomy. RESULTS: EUS was more sensitive than US in
      detecting gallbladder stones (100% vs. 84%, p < 0.005). The sensitivities of ERCP
      and EUS for choledocholithiasis were both 97%, and the overall accuracies were
      96% and 98%, respectively, with no significant difference. EUS detected the
      absence of choledocholithiasis in 65 of 66 patients (specificity = 98%).
      Endosonographic examination was successful in all patients, whereas ERCP was
      unsuccessful in 5 patients (p > 0.05). Post-endoscopic sphincterotomy bleeding
      developed in 4 patients; there was no EUS-related morbidity (p > 0.05).
      CONCLUSION: EUS is more sensitive than US in detecting biliary stones in patients
      with acute pancreatitis. It is as accurate as ERCP in detecting
      choledocholithiasis. EUS can be used to select patients with acute pancreatitis
      who require therapeutic ERCP, thus avoiding diagnostic ERCP and its associated
      potential for complications in the majority of patients.

PMID- 11522973
TI  - Frequency of mediastinal lymph node metastases in patients undergoing EUS
      evaluation of pancreaticobiliary masses.
AB  - BACKGROUND: Mediastinal lymph node metastases have rarely been reported in
      patients with pancreatic cancer. Our aim was to determine the frequency of
      mediastinal lymph node metastases in patients with pancreaticobiliary masses by
      using EUS-guided fine needle aspiration. METHODS: Sixty-six consecutive patients
      with pancreatobiliary masses were evaluated on EUS for the presence of
      mediastinal lymph node metastases. All masses were staged by commonly used EUS
      criteria by using sector scanning echoendoscopes. Mediastinal lymph nodes with
      EUS features that suggested malignancy were aspirated. RESULTS: Of the 66
      patients (mean age 65.6 years; 38 men), 4 had biliary masses, 5 had lesions of
      the major duodenal papilla, and 57 had pancreatic masses. Eleven patients (10
      pancreatic masses, 1 biliary mass) had enlarged mediastinal lymph node (12-30 mm)
      on EUS; in 2 patients these had a benign appearance and were not aspirated. Nine
      patients underwent EUS-guided fine needle aspiration: in 1 the cytology was
      inconclusive (patient subsequently had a negative Whipple resection); in 4 the
      mediastinal lymph node cytology was benign; the remaining 4 patients had
      adenocarcinoma cells in the aspirate from mediastinal lymph node. These 4
      pancreatic tumors were staged by EUS as T2N1M1 (1), as T4N0M1 (2, one later found
      to also have a lung mass), and T4N1M1 (1). CONCLUSION: Enlarged mediastinal lymph
      nodes were found on EUS in 16.6% (95% CI [7.7%, 25.6%]) of patients with
      pancreatobiliary masses and in 17.5% (95% CI [7.6%, 27.4%]) of patients with
      pancreatic masses. The frequency of mediastinal lymph node metastases in
      pancreatobiliary masses was 6.1% (95% CI [0.34%, 11.9%]) and in pancreatic masses
      7.0% (95% CI [0.4%, 13.6%]). Routine EUS evaluation of the mediastinum in
      patients with pancreatic masses is warranted.

PMID- 11522974
TI  - EUS in the detection of ascites and EUS-guided paracentesis.
AB  - BACKGROUND: The utility of EUS was evaluated for detection of ascites and EUS
      guided FNA of ascites in patients undergoing EUS for diagnosis and staging of GI
      malignancies. METHODS: A series (from March 1994 to October 1997) of 571
      consecutive patients who underwent upper EUS for various indications was
      retrospectively reviewed. Follow-up clinical information was obtained from
      referring physicians, subsequent CT, and telephone interviews. RESULTS: Eighty
      five patients (15% of series) were found to have ascites by EUS. Six did not have
      CT before EUS. Pre-EUS CT identified ascites in only 14 (18%) of the 79 patients
      who had pre-EUS CT. Of the patients in whom CT was negative for abdominal fluid
      (n = 65) and who had clinical follow-up, 13 of 58 (22%) subsequently had ascites
      develop that were detected by CT or physical examination. Overall, 31 of the 85
      patients underwent EUS-guided FNA paracentesis; the mean volume obtained was 7.9
      mL (range 1-40 mL). In 5 patients, malignant ascites was diagnosed by EUS-guided
      FNA; in these patients surgery was avoided. CONCLUSIONS: EUS is more sensitive
      than CT in detecting small amounts of ascites. A significant number (22%) of
      patients who had ascites by EUS subsequently had ascites develop that was
      detectable by CT or physical examination. EUS-guided paracentesis appears to be
      safe and effective and can identify malignant ascites.

PMID- 11522976
TI  - Expression of bacterial beta-glucuronidase in human bile: an in vitro study.
AB  - BACKGROUND: Bacterial beta-glucuronidase causes deconjugation of bilirubin
      diglucuronide resulting in the precipitation of calcium bilirubinate, which
      contributes to biliary sludge and stone formation. This process is attributed to
      enzyme activity produced by the aerobic enterobacteriaceae such as Escherichia
      coli and Klebsiella sp. The presence of Clostridium sp. was detected in 48 of 56
      intrahepatic stones by using polymerase chain reaction techniques and cultured
      Clostridium perfringens from 14 of 18 unblocked biliary stents. Such bacteria are
      reported to produce beta-glucuronidase activity. The aim of this study was to
      determine the proportion of biliary bacteria isolated from pigment stones and
      stents that produce beta-glucuronidase and to compare the enzyme activity
      expressed by the different bacteria in human bile. METHODS: A total of 202
      bacteria were isolated from blocked and unblocked biliary stents and pigment
      ductal stones recovered from patients. Of these, 61 bacteria expressed beta
      glucuronidase activity in brain heart infusion broth. These 61 bacteria were
      subsequently grown in human bile under aerobic or anaerobic conditions to the
      early stationary phase and assayed for beta-glucuronidase activity by using rho
      nitrophenyl beta-D glucuronide as substrate. Results were normalized and reported
      as units of enzyme activity per milligram protein of the bacteria. RESULTS: C.
      perfringens produced beta-glucuronidase enzyme activity that was 34-fold higher
      than that for E coli, Staphylococcus, Corynebacterium sp., Bacillus sp.,
      Enterococcus sp., Acinetobacter sp., Streptococcus sp., and Klebsiella sp.
      CONCLUSION: C. perfringens with its higher enzyme activity is more important in
      the deconjugation of bilirubin diglucuronide than E coli and Klebsiella sp.

PMID- 11522975
TI  - Bacteriologic analyses of bile and brown pigment stones in patients with acute
      cholangitis.
AB  - BACKGROUND: Bacteria play an important role in the formation of brown pigment
      stones through adherence and biofilm formation. Scanning electron microscopy of
      cross sections of these stones reveals a laminated appearance and various
      bacteria in the different layers. Our postulation was that different bacteria
      might be involved at different stages of stone formation. METHODS: By using
      standard bacteriologic cultures, the composition, morphology, and antibiotic
      sensitivity patterns of bacteria isolated from paired stone were compared with
      bile samples from 70 patients with acute cholangitis. A further comparison was
      made between bacteria isolated from the periphery and center of 3 randomly
      selected brown pigment stones. RESULTS: Ninety-one percent of bile and 99% of
      stone samples yielded positive cultures, with a total of 151 and 149 bacteria
      isolated from bile and stones, respectively. In 22 patients (33%), the bacteria
      isolated from the paired bile and stone samples were totally different. The mean
      percentage similarity of bacteria isolated from bile and stones was 39% (range 0%
      100%). Of the 59 pairs of similar bacteria isolated, the antibiotic sensitivity
      patterns were different in 24 (41%) cases. Of the 3 brown stones studied, either
      different bacterial species or the same bacteria but different strains with
      different antibiotic sensitivities were isolated from the center and periphery of
      the stones. CONCLUSIONS: Bacteria present in the different layers of brown
      pigment stones may represent the bacterial flora in bile at different times.
      Simple bile culture may not identify bacteria trapped inside the stone.

PMID- 11522977
TI  - Post-fundoplication symptoms: the role for endoscopic assessment of
      fundoplication integrity.
AB  - BACKGROUND: Fundoplication is now almost exclusively a laparoscopic procedure.
      The aim of this study was the comparison of the diagnostic usefulness of
      endoscopy and barium esophagram in the detection of fundoplication abnormalities.
      METHODS: Twenty-two patients presented with symptoms post-laparoscopic (Nissen)
      fundoplication that included dysphagia (14 patients), heartburn (5 patients),
      dyspepsia (2 patients), and chest pain (1 patient). Barium esophagram and upper
      endoscopy were performed in all patients and the results were compared. Key
      features included presence of esophagitis, resistance to endoscope passage,
      location of the wrap relative to the diaphragmatic hiatus, location of
      squamocolumnar junction greater than 1 cm proximal to the wrap zone, and the
      appearance of the wrap (intact, loose, disrupted, or tight). RESULTS: The key
      features explained symptoms in 20 of 22 patients. Endoscopy detected twice as
      many key features as radiography. Disruption of the wrap or excessive proximal
      location of the squamocolumnar junction proximal to the wrap zone were the most
      incriminating endoscopic findings. Resistance to endoscope passage was rarely
      encountered and the esophagram was more accurate in detecting an overly tight
      wrap. CONCLUSIONS: Endoscopic evaluation is more accurate than barium esophagram
      in detecting post-fundoplication abnormalities. The appearance of the
      fundoplication wrap and an abnormal proximal location of the squamocolumnar
      junction appear to be major endoscopic clues in diagnosis of post-fundoplication
      problems.

PMID- 11522978
TI  - Placement of esophageal self-expanding metallic stents without fluoroscopy.
AB  - BACKGROUND: Fluoroscopy is routinely used to guide the placement of self
      expanding metallic stents for the palliative treatment of patients with
      esophageal malignancy. This is a description of a novel method of stent placement
      without fluoroscopy. METHODS: This technique relies on a clear endoscopic view of
      the proximal radiopaque marker on the stent. This was achieved by the application
      of an external white marker at this level. A gastroscope was passed, allowing
      guidewire deployment and measurement of stricture length. The endoscope was
      reinserted and placed alongside the guidewire giving direct visualization of the
      proximal margin of the stricture. The stent delivery device was positioned,
      keeping the white mark visible proximal to the stricture, and the stent was
      deployed. RESULTS: Thirty consecutive patients with inoperable esophageal
      malignancy underwent endoscopic placement of self-expanding metal stents.
      Deployment in satisfactory position without fluoroscopy was successful in 23 of
      30 (77%); there were no complications. CONCLUSIONS: The majority of esophageal
      stents can be accurately positioned without fluoroscopy.

PMID- 11522979
TI  - Churg-Strauss syndrome with multiple colorectal tiny erosions.

PMID- 11522980
TI  - Biliary-duodenal fistula caused by metal stent.

PMID- 11522981
TI  - Hemobilia-induced occlusion of a biliary metal expandable stent.

PMID- 11522982
TI  - Hemosuccus pancreaticus: dorsal pancreatic duct stone and gastroduodenal artery
      pseudoaneurysm.

PMID- 11522983
TI  - Knitted nitinol stent insertion for various intestinal stenoses with a modified
      delivery system.
AB  - BACKGROUND: Insertion of metallic stents for esophageal stenoses is well
      established, but these stents are technically difficult to place elsewhere in the
      GI tract. Moreover, major complications have occurred when metal stents with
      sharp ends have been placed in these locations. The currently available flexible,
      blunt-ended, knitted nitinol stent is intended for use only in the esophagus.
      Because its short delivery system cannot reach segments of the gut distal to the
      esophagus, the delivery device was modified to facilitate intestinal access, and
      its performance was evaluated in the treatment of malignant intestinal
      obstructions. METHODS: The Ultraflex delivery system was modified by connecting
      an additional plastic tube and a suture cord; the length was increased from 95 cm
      to 150 cm or more. Stents used were 18 to 23 mm in diameter, and 10 to 15 cm in
      length. A knitted metal stent was inserted by using the modified delivery system
      in 10 patients (7 men, 3 women, mean age 68 years); 8 with gastric outlet, 1 with
      jejunal, and 1 with proximal colonic obstruction. RESULTS: Metal stent insertion
      was successful in all patients with significant relief of symptoms and
      restoration of the ability to eat. The patient with a jejunal stent required
      placement of a second stent because of bending of the initial stent. No major
      complications (migration or perforation) occurred. CONCLUSION: This technique
      appears to facilitate placement of a metal stent with blunt ends in the duodenum,
      small intestine, and proximal colon. Manufacturers should offer blunt-ended
      stents with long delivery devices.

PMID- 11522984
TI  - Combined antegrade and retrograde dilation: a new endoscopic technique in the
      management of complex esophageal obstruction.
AB  - BACKGROUND: Esophageal strictures that cause complete obstruction are often
      difficult to dilate with standard bougienage techniques. METHODS: A new technique
      was developed and applied, combined antegrade and retrograde dilation, for
      dilatation of complex esophageal strictures. The stomach is accessed and an
      endoscope (9.8 mm diameter) is directed under fluoroscopy in a retrograde fashion
      into the distal esophagus. A guidewire with a hydrophilic coating is advanced
      through the stricture and then pulled through the mouth with a simultaneously
      placed proximal endoscope. The guidewire is then used as a guide for antegrade
      esophageal dilatation. RESULTS: Ten patients with complex esophageal strictures
      (with and without fistulas) were treated with this technique. Three required a
      second combined antegrade and retrograde dilation procedure. All strictures were
      dilated and no perforations occurred. CONCLUSIONS: Combined antegrade and
      retrograde dilation is a safe and effective technique for dilation of complex
      obstructing esophageal lesions.

PMID- 11522985
TI  - EUS and histopathologic correlates in eosinophilic esophagitis.

PMID- 11522986
TI  - Cholesterol crystal embolization presenting as a colonic pseudotumor: case report
      and review.

PMID- 11522987
TI  - Biliary pneumonitis after proximal stent migration.

PMID- 11522988
TI  - Videoendoscopy with vital double dye staining (crystal violet and methylene blue)
      for detection of a minute focus of early stage adenocarcinoma in Barrett's
      esophagus: a case report.

PMID- 11522989
TI  - Proximal extension of cap polyposis confirmed by colonoscopy.

PMID- 11522990
TI  - Recurrence after endoscopic polypectomy of sigmoid colon carcinoma with
      submucosal invasion.

PMID- 11522991
TI  - Placement of additional stent for recanalizing procedure of occluded jejunal
      stent.

PMID- 11522992
TI  - Post-traumatic inflammatory pseudotumor of the esophagus.

PMID- 11522993
TI  - Gastric drainage of postoperative biloma.

PMID- 11522995
TI  - Methylene blue chromoendoscopy for Barrett's esophagus: coming soon to your GI
      unit?

PMID- 11522994
TI  - Endoscopic drape to avoid contamination of the operative field during laparotomy
      assisted endoscopy.

PMID- 11522996
TI  - Sky blue or murky waters: the diagnostic utility of methylene blue.

PMID- 11522997
TI  - Endoscopic sphincterotomy from a worldwide perspective.

PMID- 11522998
TI  - Placement of esophageal self-expandable metallic stents without fluoroscopy.

PMID- 11522999
TI  - Removal of traction-removable gastrostomy tubes with local anesthetic.

PMID- 11523000
TI  - Sunflower seed rectal bezoar in an adult.

PMID- 11523001
TI  - Lower endoscopy after curative colorectal cancer surgery: it's not just cancer
      surveillance.

PMID- 11523002
TI  - The analysis of clinical studies: the use of nonparametric techniques.

PMID- 11523003
TI  - Structural features of the mdg1 lineage of the Ty3/gypsy group of LTR
      retrotransposons inferred from the phylogenetic analyses of its open reading
      frames.
AB  - The increasing amount of data generated in recent years has opened the way to
      exhaustive studies of the relationships among different members of the Ty3/gypsy
      group of LTR retrotransposons, a widespread group of eukaryotic transposable
      elements. Former research led to the identification of several independent
      lineages within this group. One of the worse represented of them is that of mdg1,
      integrated so far only by the Drosophila retrotransposons mdg1 and 412. Our
      exhaustive database searches indicate the existence of three other Drosophila
      members of this lineage. Two of them correspond to elements already known,
      namely, Stalker and blood, but the third one is a new element, which we have
      called Pilgrim. This element is well represented within the D. melanogaster
      genome, as revealed by our Southern blot analysis of different strains. The case
      of Stalker is particularly remarkable, since its phylogenetic relationships
      clearly point to the mosaic origin of its genome. Finally, our analysis of the
      evolution of a small ORF preserved within the 5' leader region of these elements
      indicates different evolutionary rates, presumably as a result of distinct
      selective constraints.

PMID- 11523004
TI  - Common history at the origin of the position-function correlation in
      transcriptional regulators in archaea and bacteria.
AB  - Regulatory proteins in Escherichia coli with a helix-turn-helix (HTH) DNA binding
      motif show a position-function correlation such that repressors have this motif
      predominantly at the N terminus, whereas activators have the motif at the C
      terminus extreme. Using this initial collection we identified by sequence
      comparison the exhaustive set of transcriptional regulators in 17 bacterial and 6
      archaeal genomes. This enlarged set shows the same position-function correlation.
      The main question we address is whether this correlation is the result of common
      origin in evolution or the result of convergence. Evidence is presented
      supporting a common history at the origin of this correlation. We show the
      existence of a supergroup of eight repressor protein families sharing a conserved
      extended sequence comprising the classic HTH. Two of these repressor families
      (MarR and AsnC) originated before the divergence of Archaea and Bacteria. They
      are proposed at the origin of HTH-bearing transcriptional regulators currently
      present in Bacteria. The group of LysR proteins, with the HTH also at the N
      terminus, offers a control to the argument, since it shows clearly distinctive
      structural, functional, and evolutionary properties. This group of activator
      proteins, suggested to have originated within the Bacteria, has an advantageous
      gene organization to facilitate its horizontal transfer-used to conquer some
      Archaea-as well as negative autoregulation convenient for homeostasis, all of
      which agrees with this being the largest family in Bacteria. These results
      suggest that if shuffling of motifs occurred in Bacteria, it occurred only early
      in the history of these proteins, as opposed to what is observed in eukaryotic
      regulators.

PMID- 11523005
TI  - Special evolutionary properties of genes encoding a protein with a simple amino
      acid repeat.
AB  - We have examined the evolution of a gene, SM50, encoding a component of the
      spicule matrix, which plays an integral role in the formation of the echinoderm
      skeleton. This gene was originally characterized in Strongylocentrotus purpuratus
      and encodes an imperfect tandem repeat of six or seven amino acids. We have
      analyzed the sequence of this repeat in a number of sea urchin species and have
      determined that the repeat regions have undergone concerted evolution. There are
      differences in the repeat region between species, but the overall repeat
      structure is conserved, suggesting the repeat forms a structural domain important
      in biomineralization. The inherent conserved amino acid repeat structure promotes
      concerted evolution due to the high probability of misreplication and unequal
      crossing-over in the repeated segment of the gene. While there are constraints on
      the amino acids allowed in the repeat region, there are also variations, so that
      the sequences observed illustrate the balance between amino acid substitutions
      and concerted evolution. We have evidence that substitutions can alter the
      mechanisms of unequal crossing-over, altering the way concerted evolution occurs.
      The way in which concerted evolution occurred appears to be determined by the
      degree of sequence similarity between the repeats in a given gene, which
      influences how unequal crossing over may occur. We have mapped the differences in
      repeat regions on existing phylogenetic trees and indicate where concerted
      evolution has taken place. We also confirm an earlier report that Hemicentrotus
      pulcherrimus fits into the Strongylocentrotus genus and examine the evolution of
      the H. pulcherrimus SM50 repeat relative to other members of this genus.

PMID- 11523006
TI  - Both the conserved and the unique gene structure of stomach-specific calpains
      reveal processes of calpain gene evolution.
AB  - The proteins nCL-2 and nCL-2' are members of the Ca2+-dependent cysteine protease
      (calpain) superfamily, with stomach-specific expression. Like other typical
      calpains, nCL-2 has three distinct domains, a protease, a C2-like, and a 5EF-hand
      Ca2+-binding domain, as well as the N-terminal propeptide region. On the other
      hand, nCL-2' lacks the C2-like and 5EF-hand domains but is otherwise identical to
      nCL-2, except for the three C-terminal residues. To examine the stomach-specific
      and presumed alternative expression mechanisms of nCL-2 and nCL-2', we have
      cloned and characterized the mouse gene for nCL-2 and nCL-2'. The mouse nCL-2
      gene contains at least 23 exons, spanning more than 50 kb, and possesses an exon
      specific for nCL-2' in the middle. Therefore, nCL-2 and nCL-2' are generated by
      alternative splicing of the same gene, Capn8. Capn8 shows the highly conserved
      gene organization of the other typical calpain large subunit genes, CAPN1, CAPN2,
      CAPN3, CAPN9, CAPN11, and Capn12, except for the unique exon between exon 9 and
      exon 10 of Capn8, which encodes the 3' half of the nCL-2' transcript. No such
      exon in the corresponding regions was found in CAPN1, CAPN2, CAPN3, CAPN9, or
      CAPN11. Gene and cDNA structures of a presumed human orthologue of mouse nCL-2,
      CAPN8, were determined, revealing that it overlaps human CAPN2, the gene for the
      m-calpain large subunit, in head-to-head orientation at 1q32-41. These features
      of Capn8 and CAPN8 illustrate a process of calpain gene evolution, i.e., the
      protease, C2-like, and 5EF-hand domains presumably functioned as independent
      genes, and the calpain superfamily has evolved by ordered fusions of these
      ancestral gene units, with subsequent amplifications.

PMID- 11523007
TI  - Dinoflagellate nuclear SSU rRNA phylogeny suggests multiple plastid losses and
      replacements.
AB  - Dinoflagellates are a trophically diverse group of protists with photosynthetic
      and non-photosynthetic members that appears to incorporate and lose endosymbionts
      relatively easily. To trace the gain and loss of plastids in dinoflagellates, we
      have sequenced the nuclear small subunit rRNA gene of 28 photosynthetic and four
      non-photosynthetic species, and produced phylogenetic trees with a total of 81
      dinoflagellate sequences. Patterns of plastid gain, loss, and replacement were
      plotted onto this phylogeny. With the exception of the apparently early-diverging
      Syndiniales and Noctilucales, all non-photosynthetic dinoflagellates are very
      likely to have had photosynthetic ancestors with peridinin-containing plastids.
      The same is true for all dinoflagellates with plastids other than the peridinin
      containing plastid: their ancestors have replaced one type of plastid for
      another, in some cases most likely through a non-photosynthetic intermediate.
      Eight independent instances of plastid loss and three of replacement can be
      inferred from existing data, but as more non-photosynthetic lineages are
      characterized these numbers will surely grow.

PMID- 11523008
TI  - Molecular evolution of calmodulin-like domain protein kinases (CDPKs) in plants
      and protists.
AB  - Many genes for calmodulin-like domain protein kinases (CDPKs) have been
      identified in plants and Alveolate protists. To study the molecular evolution of
      the CDPK gene family, we performed a phylogenetic analysis of CDPK genomic
      sequences. Analysis of introns supports the phylogenetic analysis; CDPK genes
      with similar intron/exon structure are grouped together on the phylogenetic tree.
      Conserved introns support a monophyletic origin for plant CDPKs, CDPK-related
      kinases, and phosphoenolpyruvate carboxylase kinases. Plant CDPKs divide into two
      major branches. Plant CDPK genes on one branch share common intron positions with
      protist CDPK genes. The introns shared between protist and plant CDPKs presumably
      originated before the divergence of plants from Alveolates. Additionally, the
      calmodulin-like domains of protist CDPKs have intron positions in common with
      animal and fungal calmodulin genes. These results, together with the presence of
      a highly conserved phase zero intron located precisely at the beginning of the
      calmodulin-like domain, suggest that the ancestral CDPK gene could have
      originated from the fusion of protein kinase and calmodulin genes facilitated by
      recombination of ancient introns.

PMID- 11523009
TI  - Why are translationally sub-optimal synonymous codons used in Escherichia coli?
AB  - Natural selection favors certain synonymous codons which aid translation in
      Escherichia coli, yet codons not favored by translational selection persist. We
      use the frequency distributions of synonymous polymorphisms to test three
      hypotheses for the existence of translationally sub-optimal codons: (1) selection
      is a relatively weak force, so there is a balance between mutation, selection,
      and drift; (2) at some sites there is no selection on codon usage, so some
      synonymous sites are unaffected by translational selection; and (3)
      translationally sub-optimal codons are favored by alternative selection pressures
      at certain synonymous sites. We find that when all the data is considered, model
      1 is supported and both models 2 and 3 are rejected as sole explanations for the
      existence of translationally sub-optimal codons. However, we find evidence in
      favor of both models 2 and 3 when the data is partitioned between groups of amino
      acids and between regions of the genes. Thus, all three mechanisms appear to
      contribute to the existence of translationally sub-optimal codons in E. coli.

PMID- 11523010
TI  - Evolutionary dynamics of the human endogenous retrovirus family HERV-K inferred
      from full-length proviral genomes.
AB  - Several distinct families of endogenous retroviruses exist in the genomes of
      primates. Most of them are remnants of ancient germ-line infections. The human
      endogenous retrovirus family HERV-K represents the unique known case of
      endogenous retrovirus that amplified in the human genome after the divergence of
      human and chimpanzee lineages. There are two types of HERV-K proviral genomes
      differing by the presence or absence of 292 bp in the pol-env boundary. Human
      specific insertions exist for both types. The analyses shown in the present work
      reveal that several lineages of type 1 and type 2 HERV-K proviruses remained
      transpositionally active after the human/chimpanzee split. The data also reflect
      the important role of mosaic evolution (either by recombination or gene
      conversion) during the evolutionary history of HERV-K.

PMID- 11523011
TI  - Limitations of compositional approach to identifying horizontally transferred
      genes.
AB  - Genes with atypical G+C content and pattern of codon usage in a certain genome
      are possibly of exotic origin, and this idea has been applied to identify
      horizontal events. In this way, it was postulated that a total of 755 genes in
      the E. coli genome are relics of horizontal events after the divergence of E.
      coli from the Salmonella lineage 100 million years ago (Lawrence and Ochman,
      1998). In this paper we propose a new way to study sequence composition more
      thoroughly. We found that although the 755 genes differ in composition from other
      genes in the E. coli genome, the difference is minor. If we accepted that these
      genes are horizontally transferred, then (1) it would be more likely that they
      were transferred from genomes evolutionarily closely related to E. coli; but (2)
      the dating method used by Lawrence and Ochman (1997, 1998) largely underestimated
      the average age of introduced sequences in the E. coli genome, in particular,
      most of the 755 genes should be introduced into E. coli before, instead of after,
      the divergence of E. coli from the Salmonella lineage. Our study reveals that
      atypical G+C content and pattern of codon usage are not reliable indicators of
      horizontal gene transfer events.

PMID- 11523012
TI  - Viral eukaryogenesis: was the ancestor of the nucleus a complex DNA virus?
AB  - In the theory of viral eukaryogenesis I propose here, the eukaryotic nucleus
      evolved from a complex DNA virus. It is proposed that the virus established a
      persistent presence in the cytoplasm of a methanogenic mycoplasma and evolved
      into the eukaryotic nucleus by acquiring a set of essential genes from the host
      genome and eventually usurping its role. It is proposed that several
      characteristic features of the eukaryotic nucleus derive from its viral ancestry.
      These include mRNA capping, linear chromosomes, and separation of transcription
      from translation. In the model, phagocytosis and other membrane fusion-based
      processes are derived from viral membrane fusion processes and evolved in concert
      with the nucleus. The coevolution of phagocytosis and the nucleus rendered much
      of the host archaeal genome redundant since the protoeukaryote could obtain raw
      materials and energy by engulfing bacterial syntrophs/prey. This redundancy
      allowed loss of the archaeal chromosome, generating an organism with eukaryotic
      features. The evolution of phagocytosis allowed the eukaryotes to be the first
      organisms to occupy the niche of predator.

PMID- 11523013
TI  - [It can be done without embryonal stem cells!].

PMID- 11523014
TI  - [Intracoronary, human autologous stem cell transplantation for myocardial
      regeneration following myocardial infarction].
AB  - OBJECTIVE: The regenerative potential of human autologous adult stem cells on
      myocardial regeneration and neovascularisation after myocardial infarction may
      contribute to healing of the infarction area. But no clinical application has
      previously been reported. We here describe for the first time the results of this
      method applied in a patient who had sustained an acute myocardial infarction.
      HISTORY AND CLINICAL FINDINGS: 14 hours after the onset of left precordial pain a
      46-year-old man was admitted to our hospital for interventional diagnosis and
      treatment. Coronary angiography demonstrated occlusion of the anterior descending
      branch of the left coronary artery with transmural infarction. This was treated
      by percutaneous transluminal catheter angioplasty and stent placement. THERAPY
      AND RESULTS: Mononuclear bone marrow cells of the patient were prepared and 6
      days after infaction 1,2 infinity 107 cells were transplanted at low pressure via
      a percutaneous transluminal catheter placed in the infarct-related artery. Before
      and 10 weeks after this procedure left ventricular function, infarct size,
      ventricular geometry and myocardial perfusion were measured by (201)thallium
      SPECT both at rest and on exercise, together with bull's-eye analysis, dobutamine
      stress echocardiography, right heart catheterisation and radionuclide
      ventriculography. At 10 weeks after the stem cell transplantation the transmural
      infarct area had been reduced from 24.6 % to 15.7 % of left ventricular
      circumference, while ejection fraction, cardiac index and stroke volume had
      increased by 20-30 %. On exercise the end diastolic volume had decreased by 30 %
      and there was a comparable fall in left ventricular filling pressure (mean
      pulmonary capillary pressure). CONCLUSION: These results for the first time
      demonstrate that selective intracoronary transplantation of human autologous
      adult stem cells is possible under clinical conditions and that it can lead to
      regeneration of the myocardial scar after transmural infarction. The therapeutic
      effects may be ascribed to stem cell-associated myocardial regeneration and
      neovascularisation.

PMID- 11523016
TI  - [Changes in penile blood flow during cycling--how does one prevent a decreased
      perfusion?].
AB  - BACKGROUND AND OBJECTIVES: An increased incidence of erectile dysfunction has
      been observed in cycling enthusiasts. Compression of the perineal region during
      cycling seems to cause decreased penile perfusion. The resulting hypoxaemia in
      the corpus cavernosum is associated with penile fibrosis, which leads in the long
      run to erectile dysfunction. This study set out to determine if cycling can cause
      changes in penile perfusion and, if so, what precautions can be taken to avoid
      any associated health hazards, including whether various saddle forms and designs
      might influence penile blood flow. COHORTS AND METHODS: In 100 healthy athletic
      men (aged 36 +/- 6.2 years) transcutaneous penile oxygen pressure (tpO (2)) at
      the glans penis was measured during cycling in different positions and with
      different types of saddle, using a modified Clark oxygen electrode. RESULTS: The
      penile blood supply decreased significantly during cycling in a seated position.
      Cycling in a standing or reclining position (on a reclining bicycle) did not lead
      to any decrease in penile blood flow. Saddle width was the most important factor
      for ensuring adequate penile perfusion while cycling in a seated position.
      CONCLUSION: This study demonstrates that changing from a seated to a standing
      position during cycling leads to a significant increase in penile perfusion.
      Therefore we suggest frequent changes from a seated to a standing position during
      cycling. Additionally we suggest taking sufficient breaks during prolonged and
      vigorous bike tours, in order to avoid any possible health hazards. Another, not
      yet widespread, alternative for avoiding a reduction in penile blood flow is
      cycling on a reclining bicycle.

PMID- 11523017
TI  - [Acute gastrointestinal bleeding caused by distinct small intestinal
      diverticulosis].
AB  - HISTORY AND CLINICAL FINDINGS: A 58-year-old man was admitted to our hospital
      after an acute onset of rectal bleeding. He was known to have had recurrent
      duodenal ulcerative disease, once with upper gastrointestinal haemorrhage.
      Clinical examination was remarkable only for rectal bleeding. INVESTIGATIONS:
      After application of a nasogastric tube cherry-red blood was evacuated. Upper
      endoscopy showed only very small mucosal erosion in the stomach and coloscopy
      demonstrated several non-bleeding diverticula. Small bowel enteroclysis showed
      severe diverticulosis of the duodenum and jejunum. DIAGNOSIS, TREATMENT AND
      COURSE: We assumed that the extensive duodenojejunal diverticulosis was the most
      probable cause of this episode of gastrointestinal bleeding because of
      simultaneous signs of upper and lower gastrointestinal haemorrhage. Because this
      was the first such episode we preferred a conservative approach. At nineteen
      months follow-up there was no recurrence of bleeding. CONCLUSION:
      Gastrointestinal hemorrhage is a common cause of hospitalization. After exclusion
      of the more common bleeding sources small bowel diverticula should be considered
      as a possible rare cause. Surgical resection of the bleeding bowel part is the
      procedure of choice, but one of the major problems in such cases is to locate
      exactly the bleeding site. If the location is uncertain, a more conservative
      approach may be preferable, especially in haemodynamically stable patients with
      first-time diverticular bleeding.

PMID- 11523018
TI  - [Cerebral vasculitis as the initial manifestation of systemic lupus
      erythematosus].
AB  - HISTORY AND CLINICAL FINDINGS: A 41-year-old man was admitted to the hospital
      because of a series of seizures. History revealed increasing weakness and
      generalized myalgia following a severe respiratory tract infection three months
      previously. The clinical examination was dominated by reduced alertness and
      cognitive impairment. INVESTIGATIONS: Positive ANA titres pointed to an
      autoimmune disease; further laboratory tests revealed an antiphospholipid
      syndrome. The clinical diagnosis of systemic lupus erythematosus was supported by
      renal biopsy. Transcranial Doppler sono-graphy and magnetic resonance imaging
      with angiography revealed cerebral vasculitis with multiple intracerebral grey
      and white matter lesions. TREATMENT AND COURSE: In addition to an
      immunosuppressive therapy with corticosteroids and intravenous pulses of high
      dose cyclophosphamide, oral anticoagulation was given in order to prevent
      thromboembolic complications. Seizures were treated with valproate. A follow-up
      MRI revealed multiple glial cell reactions and reduced vasculitic changes.
      CONCLUSIONS: Initial neuropsychiatric symptoms and seizures prompted the
      diagnosis of systemic lupus erythematosus with cerebral vasculitis in a 41-year
      old patient. Approximately 20 % of all lupus patients initially present with
      neuropsychiatric disorders. Central nervous system involvement and renal
      complications determine the course and prognosis of the disease as well as
      therapeutic decisions. Particularly in young patients with neuropsychiatric
      symptoms systemic lupus erythematosus should be excluded routinely.

PMID- 11523019
TI  - [Glitazone--a new class of drugs for the treatment of type 2 diabetes].

PMID- 11523020
TI  - [Diagnosis of vascular ectasias of the gastric antrum (watermelon stomach)].

PMID- 11523021
TI  - [Whipple's disease--a rare systemic disease. Current status of diagnosis and
      treatment].

PMID- 11523022
TI  - Cancer therapy. New strategies and treatment modalities for optimizing patient
      outcomes.
AB  - In the postgenome era, development of novel targeted therapeutics is anticipated
      to accelerate, with the promise of specifically tailored strategies to treat
      specific molecularly characterized disease entities. Greater understanding of
      disease pathophysiology and pharmacologic actions at the molecular, cellular, and
      tissue levels have provided the basis for expanding the clinical application of
      available therapies such as recombinant human erythropoietin (r-HuEPO, epoetin
      alfa). The role of epoetin alfa in anemic cancer patients receiving chemotherapy
      has grown as our understanding of the relationship between anemia and quality of
      life in this patient population has evolved. With anemia and tumor hypoxia
      associated with poorer outcomes in various solid tumors, the potential impact of
      epoetin alfa on outcomes, as well as quality of life, in patients undergoing
      radiation or chemoradiation is of considerable interest. Anemia occurs almost
      universally in critically ill patients, resulting in substantial transfusion
      requirements. In this setting, the anemia appears to be consistent with anemia of
      chronic inflammatory disease and is potentially treatable by epoetin alfa. Recent
      preclinical studies indicate that erythropoietin exhibits neuroprotective effects
      in models of central nervous system injury, suggesting additional potential novel
      clinical applications for epoetin alfa worthy of careful investigation. Advances
      in the understanding of the ras genes and their functional proteins in signaling
      pathways involved in the development of cancer, particularly hematologic
      malignancies, over the last decade have prompted development of a new class of
      agents, farnesyl protein transferase inhibitors (FTIs), designed specifically to
      inhibit the initial step in Ras protein activation. Initial clinical evaluation
      of FTIs is ongoing, and preliminary results demonstrate antitumor activity in
      hematologic malignancies. Further identification and understanding of the
      function and complex interactions of proteins involved in diseases holds the
      promise of targeted therapies and improved patient outcomes.

PMID- 11523023
TI  - The negative impact of anemia on radiotherapy and chemoradiation outcomes.
AB  - In cancer patients, anemia is common and has been found to impair quality of life
      and reduce locoregional disease control conferred by radiotherapy. The prognostic
      importance of anemia in the radiation oncology setting may be related to a
      reduction of molecular oxygen levels, thereby attenuating radiation-induced
      damage and ultimate cell death. Substantially higher doses of radiation are
      required to eradicate malignant cells under the hypoxic conditions commonly
      identified in solid tumors. Consistent with this, patients with hypoxic solid
      tumors have been found to have shorter postradiation disease-free survival rates
      relative to patients with well-oxygenated tumors. An attempt to enhance
      intratumoral oxygenation via correction of anemia, a highly prevalent but
      modifiable condition, is therefore a reasonable approach to optimize radiotherapy
      and chemoradiation outcomes. Clinical studies investigating recombinant human
      erythropoietin (epoetin alfa) as an adjunct to radiotherapy have demonstrated its
      ability to increase and maintain hemoglobin (Hb) levels during the course of
      radiotherapy. In a study involving anemic patients undergoing chemoradiation for
      head and neck cancer, epoetin alfa extended locoregional control and survival to
      rates reported for patients with normal pretreatment Hb levels. Given the high
      prevalence and prognostic significance of anemia during radiotherapy, strategies
      that safely and effectively increase Hb levels may be of value for optimizing
      radiotherapy and chemoradiation outcomes.

PMID- 11523024
TI  - Farnesyl protein transferase inhibitors as targeted therapies for hematologic
      malignancies.
AB  - Farnesyl protein transferase inhibitors (FTIs) represent a new class of
      anticancer agents specifically targeting aberrant biologic processes involved
      with cellular transformation and malignancy. Originally developed to inhibit
      tumors by preventing activation of oncogenic ras genes via suppression of their
      posttranslational farnesylation, their anticancer activity appears to stem from
      their ability to inhibit farnesylation of various proteins that mediate signal
      transduction, growth, apoptosis, and angiogenesis. The safety, biologic activity,
      clinical response, and pharmacokinetics of R115777, a potent, orally active FTI,
      were recently investigated in a phase I dose-ranging study in patients with acute
      leukemias. Patients with acute myelogenous leukemia (AML), acute lymphocytic
      leukemia (ALL), or chronic myelogenous leukemia (CML) in blast crisis received
      R115777 100 mg, 300 mg, 600 mg, 900 mg, or 1,200 mg twice daily for 21 days.
      Cycles were repeated every 28 to 31 days for up to four cycles. An overall
      response rate of 29% (10/34 evaluable patients) was observed across all R115777
      doses. R115777 was well tolerated; common adverse events included fatigue,
      increased creatinine, nausea, and neutropenia. Dose-limiting toxicity occurred at
      1,200 mg twice daily. Farnesylation of lamin A and HDJ-2, examined as biologic
      end points, was inhibited by R115777 doses > or = 600 mg twice daily.
      Pharmacokinetic evaluation suggests that R115777 is concentrated in bone marrow
      at steady state. The biologic and antitumor activity and favorable tolerability
      of R115777 support further clinical evaluation alone and in combination therapy
      in hematologic malignancies.

PMID- 11523025
TI  - Anemia in the critically ill: the role of erythropoietin.
AB  - Anemia is a common clinical problem in critically ill patients and is associated
      with substantial red blood cell (RBC) transfusion requirements. However, RBC
      transfusion has significant risks, including adverse effects on the immune
      system. Although a low hemoglobin concentration may be tolerable, it may not be
      optimal for the critically ill patient. Thus, alternative therapies that can
      increase hemoglobin and avoid complications of RBC transfusion are desirable.
      Critically ill patients appear to have anemia identical to the anemia of chronic
      inflammatory disease with blunted erythropoietin production. Results of a recent
      randomized controlled trial in critically ill patients demonstrated that
      recombinant human erythropoietin (r-HuEPO, epoetin alfa) significantly reduced
      (by approximately 50%) the number of RBC units transfused (P <.002) and
      significantly increased hematocrit (P <.01) compared with placebo. There was no
      increase in mortality or adverse clinical events with therapy. Epoetin alfa may
      be an effective therapeutic approach to anemia in critically ill patients,
      decreasing the need for transfusion and achieving higher hemoglobin
      concentrations than generally attained with transfusion.

PMID- 11523026
TI  - Beyond erythropoiesis: novel applications for recombinant human erythropoietin.
AB  - Erythropoietin (EPO) primarily is produced in the kidney and acts as a principal
      mediator of the physiologic response to hypoxia by increasing red blood cell
      production. Astrocytes and neurons in the central nervous system (CNS) also are
      known to produce EPO in response to hypoxia/ischemia. EPO appears to play a
      neuroprotective role based on preclinical data demonstrating the ability of
      recombinant human erythropoietin (r-HuEPO) to shield neurons from
      hypoxic/ischemic stress when administered intracerebraventricularly. In CNS
      models, systemically administered r-HuEPO has not been intensely investigated
      because large glycosylated molecules generally were deemed incapable of crossing
      the blood-brain barrier (BBB). A collaborative research effort identified
      expression of EPO receptors on human brain capillaries and a specific receptor
      mediated transport of r-HuEPO across the BBB after a single intraperitoneal (IP)
      injection in rodents, with subsequent protection against various types of
      neuronal damage. For example, administration of r-HuEPO 24 hours before or up to
      6 hours after focal ischemic stroke significantly reduced the extent of
      infarction. r-HuEPO also attenuated concussive brain injury, kainate-induced
      seizure activity, and autoimmune encephalomyelitis. These preclinical findings
      suggest that r-HuEPO may have therapeutic potential for stroke, head trauma, and
      epilepsy; additional studies are needed to confirm and extend these encouraging
      observations in animal models.

PMID- 11523027
TI  - Biomimetic coprecipitation of calcium phosphate and bovine serum albumin on
      titanium alloy.
AB  - Titanium alloy implants were precoated biomimetically with a thin and dense layer
      of calcium phosphate and then incubated either in a supersaturated solution of
      calcium phosphate or in phosphate-buffered saline, each containing bovine serum
      albumin (BSA) at various concentrations, under physiological conditions for 48 h.
      Coated implants then underwent scanning electron microscopy, immunohistochemical
      evaluation, Fourier transform infrared spectroscopy, and X-ray diffraction. The
      quantity of BSA taken up by coatings and the kinetics of protein release were
      monitored colorimetrically. In coatings prepared by the coprecipitation of
      calcium phosphate and BSA, protein had become incorporated into the mineral
      crystal latticework. With increasing BSA concentration, matrices decreased in
      thickness, became more dense, showed lower crystallinity, and underwent a change
      in crystal geometry. The octacalcium phosphate structure manifested in the
      absence of protein was gradually transformed into a carbonated apatite form.
      Preformed mineral coatings became only superficially mantled with a layer of BSA,
      and the morphology of the mineral matrices themselves remained unchanged. At
      equivalent protein concentrations, coatings prepared by the coprecipitation of
      calcium phosphate released only a minute fraction of its protein component under
      physiological conditions, whereas preformed mineral matrices showed a "burst"
      release of their associated protein within a single 2-h period. The biomimetic
      coating can be a carrier for osteoinductive agents.

PMID- 11523028
TI  - The effects of surface chemistry and adsorbed proteins on monocyte/macrophage
      adhesion to chemically modified polystyrene surfaces.
AB  - Monocytes and macrophages play critical roles in inflammatory responses to
      implanted biomaterials. Monocyte adhesion may lead to macrophage activation and
      the foreign body response. We report that surface chemistry, preadsorbed
      proteins, and adhesion time all play important roles during monocyte adhesion in
      vitro. The surface chemistry of tissue culture polystyrene (TCPS), polystyrene,
      Primaria, and ultra low attachment (ULA) used for adhesion studies was
      characterized by electron spectroscopy for chemical analysis. Fibrinogen
      adsorption measured by (125)I-labeled fibrinogen was the lowest on ULA, higher on
      TCPS, and the highest on polystyrene or Primaria. Monocyte adhesion on protein
      preadsorbed surfaces for 2 h or 1 day was measured with a lactate-dehydrogenase
      method. Monocyte adhesion decreased over time. The ability of preadsorbed
      proteins to modulate monocyte adhesion was surface dependent. Adhesion was the
      lowest on ULA, higher and similar on TCPS or polystyrene, and the highest on
      Primaria. Monocyte adhesion on plasma or fibrinogen adsorbed surfaces correlated
      positively and linearly to the amount of adsorbed fibrinogen. Preadsorbed
      fibronectin, immunoglobulin G, plasma, or serum also promoted adhesion compared
      with albumin preadsorbed or uncoated surfaces. Overall, biomaterial surface
      chemistry, the type and amount of adsorbed proteins, and adhesion time all
      affected monocyte adhesion in vitro.

PMID- 11523029
TI  - Development of an artificial dermis preparation capable of silver sulfadiazine
      release.
AB  - This article describes the antibacterial effects of an artificial dermis
      impregnated with silver sulfadiazine (Ag-SD) in vitro as well as in vivo. In the
      in vitro test, silver release from the artificial dermis impregnated with Ag-SD,
      by immersion in collagenase solution was controlled by the degradation of the
      collagen sponge. The artificial dermis impregnated with 3% or higher doses of Ag
      SD completely suppressed the growth of Pseudomonas aeruginosa (Ps.) or
      Staphylococcus aureus (St.). The cytotoxicity test revealed that impregnation of
      5% or higher doses of Ag-SD suppressed the growth of fibroblasts. However, when
      the artificial dermis impregnated with Ag-SD was implanted into full-thickness
      skin defects on the backs of guinea pigs, no tissue damage was histologically
      observed around the implanted site of the dermis. In the in vivo test, the
      artificial dermis impregnated with 10% Ag-SD, which was grafted on experimentally
      contaminated wounds in the backs of guinea pigs, macroscopically suppressed
      degradation of the collagen sponge, and significantly reduced the growth of both
      Ps. and St., compared with artificial dermis without Ag-SD. We conclude that
      collagen sponge impregnated with Ag-SD is a promising artificial dermis
      applicable to treat contaminated wounds.

PMID- 11523030
TI  - Effect of albumin on brushite transformation to hydroxyapatite.
AB  - Brushite (CaHPO(4) x 2H(2)O) is a precursor to hydroxyapatite [HA,
      Ca(5)(PO(4))(3)OH]. It has been shown that a modified form of brushite, with
      potassium substituting for calcium at specific sites, demonstrated accelerated
      transformation to HA when exposed to nonproteinaceous Hanks' balanced aqueous
      salt solutions (HBSS). The biocompatibility of a transforming material is related
      to cellular response to the process, which is initiated by protein adsorption.
      The effect of adsorbed protein on the kinetics and chemistry of brushite
      transformation to HA, when exposed to HBSS containing bovine serum albumin (BSA),
      was examined using Fourier transform IR spectroscopy, X-ray diffraction, and
      energy dispersive spectrometry techniques. The effect of solution pH was also
      studied. Results show that, in the presence of a protein-free environment,
      transformation is faster in buffered medium than in nonbuffered medium. Moreover,
      curve fitting and second derivatives of the IR spectra show that some bands shift
      depending on whether the brushite transforms in a buffered or nonbuffered medium.
      Therefore, variation in pH affects both transformation rate and the associated
      chemistry. The presence of BSA in either buffered or nonbuffered medium retards
      the transformation in comparison to the corresponding BSA-free medium. The extent
      of this retardation increases with the increase in bulk concentration of BSA but
      does not alter the transformation chemistry. This suggests the retardation on the
      transformation rate is due to BSA adsorption coverage on the calcium phosphate
      ceramic. This may be due to the shielding of Ca(2+) and PO(4)(-3) sites,
      preventing their interaction with the HBSS.

PMID- 11523031
TI  - Manipulation of selective cell adhesion and growth by surface charges of
      electrically polarized hydroxyapatite.
AB  - Adherence of cells to a surface, such as a biomaterial surface, can be
      significantly influenced by the surface charge on that material. The
      applicability of electrically charged hydroxyapatite ceramics to selective cell
      adhesion was examined, and we show that polarized hydroxyapatite has significant
      effects on cell growth and adhesion. The surface charge applied to polarized
      hydroxyapatite promotes (i) enhanced colony formation of osteoblast-like cells,
      (ii) activation of gap junctions, and (iii) specific orienting of neuroblastoma
      cells. These findings will be of great utility and have significance in
      applications of tissue engineering, for example, in potential treatments for
      osteoporosis.

PMID- 11523032
TI  - The effect of host factors and capsule composition on the cellular overgrowth on
      implanted alginate capsules.
AB  - Microencapsulation of islets of Langerhans in alginate/poly-L-lysine
      (PLL)/alginate capsules may provide a method for transplantation in the absence
      of immunosuppression. The aim of this study was to investigate the problem of
      overgrowth on implanted capsules with regard to the composition of the capsules
      and host factors such as cytokine and nitric oxide production. Empty capsules
      were implanted to C57BL/6 mice for 1, 3, 7, or 28 days. Glucose oxidation rates
      showed the metabolic activity of the cellular overgrowth on retrieved capsules.
      DNA content, histological score, and retrieval rates were also measured to assess
      the overgrowth. It was noted that the pericapsular host reaction arose by day 7
      and had not increased further by day 28. Capsules of varying alginate
      compositions and different concentrations of PLL were implanted for 7 days to
      either C57BL/6 or Balb/c mice. Capsules were also implanted to mice lacking the
      inducible nitric oxide synthase enzyme. Glucose oxidation rates, DNA content, and
      histological score were positively correlated to each other and negatively
      correlated to retrieval rates. The pericapsular reaction was reduced if PLL was
      omitted from the capsule or if a high mannuronic acid alginate was used. Balb/c
      mice had reduced cellular overgrowth on implanted capsules and had reduced mRNA
      expression of interleukin-1 beta and tumor necrosis factor-alpha in their
      peritoneal macrophages. The capsular overgrowth seemed more severe in animals
      lacking inducible nitric oxide synthase compared with wild-type controls. It is
      concluded that alginate composition, PLL, and recipient factors such as nitric
      oxide production and cytokine expression affect the cellular overgrowth on
      implanted alginate capsules.

PMID- 11523033
TI  - Filler-coupling agent-matrix interactions in silica/polymethylmethacrylate
      composites.
AB  - The interactions of the silane coupling agent methacryloxypropyltrimethoxysilane
      (MPS) with both fumed silica and a polymethylmethacrylate (PMMA) resin matrix
      were investigated using thermogravimetric analysis and Fourier transform infrared
      spectroscopy. OX 50 fumed silica was silanated with MPS at concentrations of 1%
      and 5% in aqueous ethanol (95%), acetone, and anhydrous toluene. Methyl
      methacrylate was polymerized with the silanated fumed silica (5% wt/wt) to form
      composites. The amount of MPS adsorption on the fumed silica and the amount of
      PMMA attached to the silanated fumed silica were determined by thermogravimetric
      analysis. MPS could be removed from the fumed silica after washing with methanol,
      but not after it underwent a drying process at 25 degrees C under vacuum. After
      vacuum drying at 25 degrees C, two types of adsorbed silane were found, i.e.,
      firmly adsorbed and loosely adsorbed silane. The loosely adsorbed silane could
      desorb from silica and be incorporated into the polymer matrix through
      copolymerization with monomeric methyl methacrylate, resulting in crosslinking of
      the matrix. When the silanated silica was dried at 110 degrees C for 2 h, the
      loosely adsorbed silane was removed and the amount of firmly adsorbed silane
      increased. There was a positive correlation between the amount of firmly adsorbed
      MPS and the amount of PMMA attachment. The highest efficiency for PMMA attachment
      was found when MPS was adsorbed as a monolayer, because the loosely adsorbed
      silane did not contribute to the bonding of PMMA, and this suggested that not all
      of the double bonds of the MPS were accessible for reaction with the methacrylate
      monomer. Drying at 110 degrees C may also decrease the number of unsaturated
      double bonds of MPS.

PMID- 11523034
TI  - Three-dimensional cartilage formation by bone marrow-derived cells seeded in
      polylactide/alginate amalgam.
AB  - Bone marrow-derived cells are considered as candidate cells for cartilage tissue
      engineering by virtue of their ability to undergo chondrogenesis in vitro when
      cultured in high density or when embedded within a three-dimensional matrix in
      the presence of growth factors. This study evaluated the potential of human bone
      marrow-derived cells for cartilage tissue engineering by examining their
      chondrogenic properties within a three-dimensional amalgam scaffold consisting of
      the biodegradable polymer, poly-L-lactic acid (PLA) alone, and with the
      polysaccharide gel, alginate. Cells were suspended either in alginate or medium
      and loaded into porous PLA blocks. Alginate was used to improve cell loading and
      retention within the construct, whereas the PLA polymeric scaffold provided
      appropriate mechanical support and stability to the composite culture. Cells
      seeded in the PLA/alginate amalgams and the plain PLA constructs were treated
      with different concentrations of recombinant human transforming growth factor
      beta1 (TGF-beta 1) either continuously (10 ng/mL) or only for the initial 3 days
      of culture (50 ng/mL). Chondrogenesis was assessed at weekly intervals with
      cultures maintained for up to 3 weeks. Histological and immunohistochemical
      analysis of the TGF-beta 1-treated PLA/alginate amalgam and PLA constructs showed
      development of a cartilaginous phenotype from day 7 to day 21 as demonstrated by
      colocalization of Alcian blue staining with collagen type II and cartilage
      proteoglycan link protein. Expression of cartilage specific genes, including
      collagen types II and IX, and aggrecan, was detected in TGF-beta 1-treated
      cultures by reverse transcription-polymerase chain reaction analysis. The
      initiation and progression of chondrogenic differentiation within the polymeric
      macrostructure occurred with both continuous and the initial 3-day TGF-beta 1
      treatment regimens, suggesting that key regulatory events of chondrogenesis take
      place during the early period of cell growth and proliferation. Scanning electron
      microscopy revealed abundant cells with a rounded morphology in the PLA/alginate
      amalgam. These findings suggest that the three-dimensional PLA/alginate amalgam
      is a potential candidate bioactive scaffold for cartilage tissue engineering
      applications.

PMID- 11523035
TI  - Impact of a nickel-reduced stainless steel implant on striated muscle
      microcirculation: a comparative in vivo study.
AB  - The impairment of skeletal muscle microcirculation by a biomaterial may have
      profound consequences. With moderately good physical and corrosion
      characteristics, implant-quality stainless steel is particularly popular in
      orthopedic surgery. However, due to the presence of a considerable amount of
      nickel in the alloy, concern has been voiced in respect to local tissue
      responses. More recently a stainless steel alloy with a significant reduction of
      nickel has become commercially available. We, therefore, studied in vivo
      nutritive perfusion and leukocytic response of striated muscle to this nickel
      reduced alloy, and compared these results with those of the materials
      conventional stainless steel and titanium. Using the hamster dorsal skinfold
      chamber preparation and intravital microscopy, we could demonstrate that
      reduction of the nickel quantity in a stainless steel implant has a positive
      effect on local microvascular parameters. Although the implantation of a
      conventional stainless steel sample led to a distinct and persistent activation
      of leukocytes combined with disruption of the microvascular endothelial
      integrity, marked leukocyte extravasation, and considerable venular dilation,
      animals with a nickel-reduced stainless steel implant showed only a moderate
      increase of these parameters, with a clear tendency of recuperation. Titanium
      implants merely caused a transient increase of leukocyte-endothelial cell
      interaction within the first 120 min, and no significant change in macromolecular
      leakage, leukocyte extravasation, or venular diameter. Pending biomechanical and
      corrosion testing, nickel-reduced stainless steel may be a viable alternative to
      conventional implant-quality stainless steel for biomedical applications.
      Concerning tolerance by the local vascular system, titanium currently remains
      unsurpassed.

PMID- 11523036
TI  - Improvement of the long-term adhesive strength between metal stem and
      polymethylmethacrylate bone cement by a silica/silane interlayer system.
AB  - A loss of adhesive strength between metal stem and bone cement is clinically
      found to be a serious problem in total hip arthroplasty and causes many operative
      revisions. The objective of this study was to improve the long-term adhesive
      strength at this interface. A new silica/silane interlayer coating system is
      introduced. The layers are designed to bond the metal stem surface to the
      polymethylmethacrylate bone cement marginally leakage free. In vitro tensile
      tests were performed on specimens of TiAl6V4 and CoCrMo that were cemented by
      pairs with different bone cements with and without the new coating system. The
      specimens were stored in isotonic saline solution up to 150 days. The adhesive
      strength decreased about 75% within 30 days of storage on specimens of both metal
      alloys that were conventionally cemented without the new interlayer system. With
      the new coating, the high initial adhesive strength (40-50 MPa) could be
      stabilized for TiAl6V4 over 150 days. For the same 150-day storage period, the
      adhesive strength of the coated CoCrMo alloy still decreased but the decrease was
      only half that experienced by the uncoated CoCrMo. The loss of adhesive strength
      on CoCrMo specimens could be reduced if the metal surface was activated by a
      plasma treatment. The new coating interface system could help to considerably
      reduce revision operations caused by debonding effects at the interface
      metal/polymethylmethacrylate bone cement.

PMID- 11523037
TI  - Shear-induced platelet activation and adhesion on human pulmonary artery
      endothelial cells seeded onto hydrophilic polymers.
AB  - We evaluated platelet activation and adhesion on two plasma polymerized surfaces,
      N-vinyl pyrrolidone (NVP) and gamma-butyro lactone (GBL), which have been shown
      previously to promote endothelial cell growth and adhesion as well as fibronectin
      coated glass (1 microg/cm(2)) coverslips. Human pulmonary artery endothelial
      cells were seeded onto coverslips at a low density ( approximately 20,000
      cells/cm(2)) and grown to confluence (3-5 days). The materials, both with and
      without ECs, were then exposed to a shear rate of 400 s(-1) in a closed loop
      recirculating flow system containing human platelet-rich plasma. Plasma samples
      were taken at 0, 5, 15, 30, and 60 min and analyzed for platelet and coagulation
      activation. The coverslips were examined for EC coverage and platelet adherence.
      EC retention over a 1-h period was approximately 75% for all three materials. All
      three materials without ECs were highly platelet activating having similar P
      selectin expression, platelet factor 4 (PF4) release, mepacrine uptake, and
      microparticle production. Both microparticle production and platelet adhesion
      were significantly lower in EC-seeded materials. Dense granule and PF4 release
      were both slightly diminished in all three materials seeded with ECs. P-selectin
      expression was reduced slightly for GBL, but remained the same for the other two
      materials. The EC-seeded materials displayed favorable characteristics with
      respect to platelet activation and adhesion; however, they still demonstrated
      some thrombogenic tendencies due to EC loss and exposure of the underlying
      substrate. Therefore, both EC coverage and EC hemostatic function are important
      factors in determining the thromboresistance of an EC-seeded surface.

PMID- 11523038
TI  - Characterization of adsorbed protein films by time of flight secondary ion mass
      spectrometry.
AB  - Time of flight secondary ion mass spectrometry (ToF-SIMS) is a useful technique
      in the study of adsorbed protein films because of its high surface sensitivity
      and chemical selectivity. However, the protein mass spectra generated by ToF-SIMS
      are complex fragmentation patterns of a polymer consisting of 20 different
      monomers (i.e., amino acids). Principal component analysis (PCA) was implemented
      to classify several reference positive ion protein spectra according to protein
      and substrate type. Furthermore, the positive ion 74/102 and 120/130 SIMS
      intensity ratios, radiolabeled experiments, and PCA were used to track the
      relative surface concentrations of bovine serum albumin and bovine fibronectin in
      a binary adsorption experiment. In all cases, the combination of ToF-SIMS and PCA
      proved capable in classifying proteins by their type (in the case of pure protein
      spectra) and relative surface concentration (in the case of the binary protein
      spectra).

PMID- 11523039
TI  - TEM-EDX study of mechanism of bonelike apatite formation on bioactive titanium
      metal in simulated body fluid.
AB  - Bioactive titanium metal, which forms a bonelike apatite layer on its surface in
      the body and bonds to the bone through the apatite layer, can be prepared by NaOH
      and heat treatments to form an amorphous sodium titanate layer on the metal. In
      the present study, the mechanism of apatite formation on the bioactive titanium
      metal has been investigated in vitro. The metal surface was examined using
      transmission electron microscopy and energy dispersive X-ray spectrometry as a
      function of the soaking time in a simulated body fluid (SBF) and complemented
      with atomic emission spectroscopy analysis of the fluid. It was found that,
      immediately after immersion in the SBF, the metal exchanged Na(+) ions from the
      surface sodium titanate with H(3)O(+) ions in the fluid to form Ti-OH groups on
      its surface. The Ti-OH groups, immediately after they were formed, incorporated
      the calcium ions in the fluid to form an amorphous calcium titanate. After a long
      soaking time, the amorphous calcium titanate incorporated the phosphate ions in
      the fluid to form an amorphous calcium phosphate with a low Ca/P atomic ratio of
      1.40. The amorphous calcium phosphate thereafter converted into bonelike
      crystalline apatite with a Ca/P ratio of 1.65, which is equal to the value of
      bone mineral. The initial formation of the amorphous calcium titanate is proposed
      to be a consequence of the electrostatic interaction of negatively charged units
      of titania, which are dissociated from the Ti-OH groups, with the positively
      charged calcium ions in the fluid. The amorphous calcium titanate is speculated
      to gain a positive charge and to interact with the negatively charged phosphate
      ions in the fluid to form the amorphous calcium phosphate, which eventually
      stabilizes into bonelike crystalline apatite.

PMID- 11523040
TI  - In vitro effects of low-intensity ultrasound stimulation on the bone cells.
AB  - Mechanical perturbations serve as extracellular signals to a variety of cells,
      including bone cells. Low-intensity pulsed ultrasound produces significant
      multifunctional effects that are directly relevant to bone formation and
      resorption. Ultrasound stimulation has been shown to accelerate bone-defect
      healing and trabecular bone regeneration. In this study, we use an in vitro bone
      cell culture model to investigate the effect of low-intensity pulsed ultrasound.
      The rat alveolar mononuclear cell-calvaria osteoblast coculture system was used
      in this study. Before treatment, the bone cells were cultured for 3 days to
      facilitate their attachment and differentiation. Then, ultrasound exposure
      (frequency = 1 MHz, intensity = 0.068 W/cm(2)) or sham exposure for 20 min per
      day was applied until the end of the experiment. Half of the culture media were
      obtained on the 4th, 5th, 6th, 7th, 8th, 9th, and 10th days for the analysis of
      cytokines and biochemical parameters. At the end of the experiment, cells were
      fixed and stained for identification and quantification of the osteoblast and
      osteoclast cells. After low-intensity pulse ultrasound stimulation, the
      osteoblast cell counts were significantly increased, whereas the osteoclast cell
      counts were significantly decreased. The total alkaline phosphatase amount in the
      culture medium was increased after 7 days of ultrasound stimulation, and tumor
      necrosis factor-alpha in ultrasound-stimulated bone cells was significantly
      increased after the 7th day of culture and reached 474.77% of the control medium
      on the 10th day of culture. The results of this study suggest that low-intensity
      ultrasound treatment may have a stimulatory effect on bone-healing processes.

PMID- 11523041
TI  - Strong and macroporous calcium phosphate cement: Effects of porosity and fiber
      reinforcement on mechanical properties.
AB  - Because of its excellent osteoconductivity and bone-replacement capability, self
      setting calcium phosphate cement (CPC) has been used in a number of clinical
      procedures. For more rapid resorption and concomitant osseointegration, methods
      were desired to build macropores into CPC; however, this decreased its mechanical
      properties. The aims of this study, therefore, were to use fibers to strengthen
      macroporous CPC and to investigate the effects of the pore volume fraction on its
      mechanical properties. Water-soluble mannitol crystals were incorporated into CPC
      paste; the set CPC was then immersed in water to dissolve mannitol, producing
      macropores. Mannitol/(mannitol + CPC powder) mass fractions of 0, 10, 20, 30, and
      40% were used. An aramid fiber volume fraction of 6% was incorporated into the
      CPC-mannitol specimens, which were set in 3 mm x 4 mm x 25 mm molds and then
      fractured in three-point flexure to measure the strength, work of fracture, and
      modulus. The dissolution of mannitol created well-formed macropores, with CPC at
      40% mannitol having a total porosity of a 70.8% volume fraction. Increasing the
      mannitol content significantly decreased the properties of CPC without fibers
      (analysis of variance; p < 0.001). The strength (mean +/- standard deviation; n =
      6) of CPC at 0% mannitol was 15.0 +/- 1.8 MPa; at 40% mannitol, it decreased to
      1.4 +/- 0.4 MPa. Fiber reinforcement improved the properties, with the strength
      increasing threefold at 0% mannitol, sevenfold at 30% mannitol, and nearly
      fourfold at 40% mannitol. The work of fracture increased by 2 orders of
      magnitude, but the modulus was not changed as a result of fiber reinforcement. A
      scanning electron microscopy examination of specimens indicated crack deflection
      and bridging by fibers, matrix multiple cracking, and frictional pullout of
      fibers as the reinforcement mechanisms. Macroporous CPCs were substantially
      strengthened and toughened via fiber reinforcement. This may help extend the use
      of CPCs with macropores for bony ingrowth to the repair of larger defects in
      stress-bearing locations.

PMID- 11523042
TI  - X-ray diffractometric determination of crystalline phase content in bioactive
      glasses.
AB  - A rapid routine determination of the content of crystalline CaF(2) and Al(2)O(3)
      inclusions in bioactive glass ceramics is performed using X-ray diffractometry
      with a standard addition technique. Multiple ratio analysis, even using peaks
      with different broadenings, indicates that differences in crystallite properties
      (e.g., crystal imperfection, particle size and morphology, preferred orientation)
      between the unknown sample and standard do not bias the result. In this respect,
      an exact match between their crystallographic integrities does not seem to be
      required for a reliable estimation of the crystalline content with a relative
      standard deviation of 7%.

PMID- 11523044
TI  - Inflammation in human skin: a model to study chemokine-mediated leukocyte
      migration in vivo.
AB  - The structure of the skin, with the preferential unidirectional migration of
      inflammatory cells from blood vessels to the dermis and eventually to the
      epidermis, its accessibility for biopsies and local manipulations, and the clear
      definition of various inflammatory disorders, makes it an ideal in vivo model
      organ to study mechanisms of leukocyte recruitment during inflammation. A report
      in this issue of the Journal studied selected inflammatory skin disorders with
      different well-characterized inflammatory profiles to study the important role of
      the T-cell-attractant chemokines Mig (CXCL9) and IP-10 (CXCL10). These chemokines
      are highly expressed and participate in the recruitment of CXC receptor 3
      (CXCR3)+ effector T-cells and their migration to the site of inflammatory
      challenge. This indicates that the chemokines Mig and IP-10 are important
      mediators for T-cell dominated inflammatory reactions in the skin.

PMID- 11523045
TI  - Are some breast carcinomas polyclonal in origin?
AB  - This editorial comments on the important study by Going et al. published in the
      present issue of the Journal [1]. Using a molecular genetic assay based on the X
      chromosome inactivation principle, they found that 4 out of 12 breast carcinomas
      examined exhibited what the authors call "clonal mosaicism" that is, two or more
      monoclonal samples were mosaic (polyclonal) in respect of X chromosome
      inactivation between separate, morphologically homogeneous tumour areas. The
      authors very carefully discuss potential methodological errors that could have
      led to this surprising finding, which seems to run counter to the almost
      unanimously held conviction that carcinomas are monoclonal in origin, but none of
      these potential errors would explain the results. As often in such situations,
      the authors prudently state that further studies using independent analytical
      techniques are necessary to find out whether a significant proportion of mammary
      carcinomas are indeed polyclonal. However, there already exists a substantial
      body of evidence from cytogenetic studies of breast cancers indicating that many
      of them are polyclonal. Although there is still room for interpretation and some
      doubt remains as to exactly which role should be ascribed to the observed clonal
      heterogeneity in our models of carcinogenesis, it seems obvious that more
      attention than before ought to be paid to this now well documented fact.

PMID- 11523046
TI  - Differential expression of CXCR3 targeting chemokines CXCL10, CXCL9, and CXCL11
      in different types of skin inflammation.
AB  - Recruitment of activated T-cells to the skin is a common feature in a wide
      variety of inflammatory skin diseases. As CXCR3 activating chemokines CXCL10 (IP
      10), CXCL9 (Mig), and CXCL11 (IP-9/I-TAC) specifically attract activated T-cells,
      this study addressed the question of whether differences in the expression of
      these chemokines correlate with the site and cellular composition of the skin
      infiltrates in different types of inflammatory skin disease. Skin biopsies from
      lichen planus, chronic discoid lupus erythematosus, allergic patch test
      reactions, psoriasis, and Jessner's lymphocytic infiltration of the skin were
      investigated for chemokine expression using RNA in situ hybridization, and for
      the expression of CXCR3 using immunohistochemistry. The results showed
      differential expression of CXCL10, CXCL9, and CXCL11, which correlated with
      differences in the localization and cellular composition of the infiltrates.
      Whereas CXCL10 and CXCL11 were mainly expressed by basal keratinoctyes, CXCL9
      mRNA expression was located predominantly in the dermal infiltrates. Correlation
      with immunohistochemical data suggested that macrophages and activated
      keratinocytes were the main producers of these chemokines. CXCR3 was expressed by
      a majority of both CD4+ and CD8+ infiltrating T-cells, suggesting a functional
      interaction between locally produced chemokines and CXCR3-expressing T-cells. In
      conclusion, these findings indicate that these CXCR3 activating chemokines play a
      significant role in the recruitment and maintenance of T-cell infiltrates in the
      inflammatory skin diseases studied.

PMID- 11523047
TI  - Clonal origins of human breast cancer.
AB  - Tumours are usually considered as the clonal progeny of single transformed cells.
      An X-chromosome inactivation assay has been applied to exploring clonal
      relationships in human breast cancer. Analysis of X-inactivation in DNA extracted
      from microdissected in situ and invasive breast carcinoma by Hpa II restriction
      and polymerase chain reaction (PCR) of the androgen receptor exon I CAG
      polymorphism confirmed monoclonality in 105/133 samples of carcinoma cells from
      31/32 informative breast cancers. Clonality was identical in seven cases between
      in situ and invasive carcinoma. Unexpectedly, 4 of 12 cancers (33%) with two or
      more monoclonal samples available were mosaic (polyclonal) in respect of X
      chromosome inactivation between separate morphologically homogeneous tumour cell
      samples. Concordant clonality supports a common clonal origin of in situ and
      invasive breast cancers, but frequent apparently mosaic X-inactivation in breast
      cancer cannot be explained by non-tumour cell contamination. It is concluded that
      these carcinomas may be genuinely multiclonal. Possible mechanisms of
      multiclonality include simultaneous transformation of cell groups straddling X
      chromosome inactivation patch boundaries, tumour-initiating mutations prior to X
      inactivation, or recruitment of bystander stem cells by DNA transfer from
      necrotic or apoptotic tumour cells. Collision of independent cancers appears
      implausible at this frequency. Further studies using independent analytical
      techniques are required to test the important possibility that a significant
      proportion of mammary carcinomas are not monoclonal.

PMID- 11523048
TI  - Expression of amphiregulin and epidermal growth factor receptor in human breast
      cancer: analysis of autocriny and stromal-epithelial interactions.
AB  - Amphiregulin (AR) and its receptor, epidermal growth factor receptor (EGFR), were
      evaluated by dual immunostaining in a series of 84 invasive ductal breast
      carcinoma specimens, 33 of which were from locally advanced inflammatory (T4d)
      cancer. Co-expression of AR and EGFR was always found in non-malignant breast
      tissues adjacent to tumours (24/24). Alternatively, expression of AR and EGFR was
      found in invasive epithelial tumour cells in 50% and 17.8% of specimens,
      respectively. In tumour stroma, 59.5% and 30.9% of specimens, respectively, were
      positively stained. By univariate analysis, AR and EGFR expression in invasive
      carcinomas was correlated with large tumour size, inflammatory carcinoma, node
      involvement, Bloom-Richardson (SBR) grade III, and absence of oestrogen receptor.
      EGFR expression in stromal cells was correlated with non-inflammatory carcinoma.
      A putative autocrine loop with AR and EGFR expression in invasive carcinoma was
      detected in 14.3% of cases. Stromal expression of AR and EGFR expression in
      invasive tumour cells was detected in 11.9% of cases and related to poor
      prognostic parameters. By multivariate analysis, AR expression in invasive tumour
      was strongly related to inflammatory carcinoma (p=0.005) and marginally related
      to SBR grade III (p=0.07). EGFR expression in invasive tumour and stromal cells
      was correlated with absence of oestrogen receptor and non-inflammatory carcinoma
      (p=0.002 and p=0.015, respectively).

PMID- 11523049
TI  - Loss of alveolar basement membrane type IV collagen alpha3, alpha4, and alpha5
      chains in bronchioloalveolar carcinoma of the lung.
AB  - Type IV collagen, the major component of basement membrane (BM), is composed of
      six genetically distinct alpha(IV) chains. This study investigated for the first
      time the expression of these six alpha(IV) chains immunohistochemically, using
      alpha(IV) chain-specific monoclonal antibodies, in normal lung and in small (less
      than 2 cm in diameter) adenocarcinoma of the lung with a bronchioloalveolar
      growth pattern at the periphery. Small adenocarcinomas were histopathologically
      classified into three subtypes: bronchioloalveolar carcinoma (BAC) without
      collapse, BAC with collapse, and adenocarcinoma with bronchioloalveolar features.
      In normal lung, alveolar BM was composed of alpha1(IV)/alpha2(IV) chains and
      alpha3(IV)/alpha4(IV)/alpha5(IV) chains. In non-collapsed areas of BAC, alveolar
      BM was composed of linear alpha1(IV)/alpha2(IV) chains and discontinuous
      alpha3(IV)/alpha4(IV)/alpha5(IV) chains. In collapsed areas of BAC, alveolar BM
      was composed of linear and thick alpha1(IV)/alpha2(IV) chains only, because of
      the complete loss of alpha3(IV)/alpha4(IV)/alpha5(IV) chains. In invasive areas
      of adenocarcinoma with bronchioloalveolar features, alpha1(IV)/alpha2(IV) chains
      around the cancer cell nests were disrupted, in addition to the complete loss of
      alpha3(IV)/alpha4(IV)/alpha5(IV) chains. In conclusion, during the process of
      stromal invasion of lung adenocarcinoma, type IV collagen of alveolar BM is
      remodelled from the complete type, composed of
      alpha1(IV)/alpha2(IV)/alpha3(IV)/alpha4(IV)/alpha5(IV) chains, to the incomplete
      type, composed of only alpha1(IV)/alpha2(IV) chains, before the disruption of
      alpha1(IV)/alpha2(IV) chains. These findings may help to clarify the molecular
      mechanisms of cancer invasion.

PMID- 11523050
TI  - Absence of tpr-met and expression of c-met in human gastric mucosa and carcinoma.
AB  - The c-met proto-oncogene, encoding the hepatocyte growth factor receptor, can be
      activated by various mechanisms. These include, among others, gene amplification
      with concomitant overexpression and the tpr-met oncogenic rearrangement. In the
      case of gastric cancer, contradictory results on the presence of the tpr-met
      oncogenic rearrangement have been published. The current study aimed therefore to
      assess the prevalence of tpr-met expression in Caucasian gastric adenocarcinomas,
      to evaluate the importance of this oncogene in their carcinogenesis. In addition,
      the level of c-met expression was determined, to evaluate the role of this
      alternative mode of activation of the proto-oncogene. A series of Caucasian
      gastric adenocarcinomas (n=43) and normal gastric mucosal samples (n=14) was
      analysed for tpr-met and c-met expression. Expression of tpr-met mRNA in the
      samples was performed by two reverse transcriptase polymerase chain reaction (RT
      PCR) assays, with excellent correlation. The specificity of both methods was
      confirmed by direct sequencing of the PCR products of the MNNG-HOS cell line,
      which is known to contain the rearrangement. The level of c-met expression was
      assessed using semi-quantitative RT-PCR assays and immunohistochemistry (IHC).
      None of the normal gastric mucosal or gastric adenocarcinoma samples expressed
      tpr-met mRNA, as determined by both RT-PCR assays. Seventy per cent of the
      adenocarcinomas showed overexpression of c-met, according to elevated c-met mRNA
      levels, compared with the expression level of normal gastric mucosa. A
      significant correlation was found between the level of c-met mRNA and protein
      expression. In conclusion, these results strongly suggest that tpr-met activation
      does not play a role in Caucasian gastric carcinogenesis, while overexpression of
      the c-met gene occurs in the majority of Caucasian gastric adenocarcinomas.

PMID- 11523051
TI  - Apoptosis and cell-cycle regulatory proteins in colorectal carcinoma:
      relationship to tumour stage and patient survival.
AB  - The quantitative assessment of apoptotic index (AI) and mitotic index (MI) and
      the immunoreactivity of p53, bcl-2, p21, and mdm2 were examined in tumour and
      adjacent normal tissue samples from 30 patients with colonic and 22 with rectal
      adenocarcinoma. Individual features and combined profiles were correlated with
      clinicopathological parameters and patient survival data to assess their
      prognostic value. Increased AI was significantly associated with increased bcl-2
      expression (p<0.008) and the immunoprofiles that included bcl-2, but not with MI,
      p53, p21 or mdm2. AI was significantly associated with increased Dukes' stage
      from A, B to C (p<0.02) but not D, while MI showed a significant association with
      all Dukes' stages (p<0.05). No significant association was found between either
      AI or MI and prognosis. p53, p21, mdm2, and bcl-2 positivity were detected in
      65.4%, 53.8%, 65.4%, and 34.6% of cases, respectively. mdm2 was significantly
      associated with p53 (p<0.03) and p21 (p<0.04) expression and p53 immunoreactivity
      was more prevalent in rectal tumours (p<0.008). In univariate survival analysis,
      bcl-2 overexpression was associated with more favourable patient survival
      (p<0.03). Positive combined patterns p53+/p21+/bcl-2+ and p21+/mdm2+/bcl-2+
      (p<0.005); p53+/bcl-2+, p21+/bcl-2+, and mdm2+/bcl-2+ (p<0.01); and p53+/p21+
      (p<0.02) were also associated with favourable clinical outcome. In multivariate
      Cox survival analysis, bcl-2 (p<0.016) and Dukes' stage (p<0.0001) were the only
      significant independent prognostic indicators. In conclusion, bcl-2
      immunoreactivity was associated with apoptosis and could be used in combination
      with Dukes' stage as a means of predicting prognosis in colorectal cancer.

PMID- 11523052
TI  - Bcl-2 expression in pancreas development and pancreatic cancer progression.
AB  - Apoptosis is important for both tissue development and differentiation; its
      deregulation may contribute to tumourigenesis. In order to clarify the role of
      Bcl-2, an apoptosis-inhibiting protein, in pancreatic morphogenesis and tumour
      progression, its immunohistochemical expression was evaluated in 12 samples of
      fetal pancreas, in 10 samples of adult pancreas with ductal hyperplastic lesions,
      in 120 cases of primary pancreatic ductal adenocarcinoma, and in 43 synchronous
      metastatic lymph nodes. To evaluate the role of apoptosis in pancreatic cancer,
      p53 expression was also studied in tumour samples. Bcl-2 cytoplasmic acinar and
      ductal immunostaining was found in all fetal and adult tissue samples; ductal
      hyperplastic lesions were constantly negative. Thirty out of 120 (25%) tumours
      and 3 out of 43 (7%) lymph nodes expressed Bcl-2, whereas 67 out of 120 (56%)
      expressed nuclear p53. Well-differentiated tumours (G1) were more frequently Bcl
      2-positive (p=0.002); furthermore, there was an inverse correlation between Bcl-2
      and p53 expression in primary tumours (p=0.02). Neither Bcl-2 nor p53 influenced
      patients' prognosis, which was instead affected by N (p=0.02) and M (p<0.0001)
      status and stage of the disease (p=0.002). It is concluded that Bcl-2 regulates
      pancreatic morphogenesis and tissue homeostasis from early fetal to adult life
      and can be considered a phenotypic marker of normal exocrine pancreas. On the
      other hand, the lack of expression in preneoplastic lesions and the low
      positivity found in primary tumours and lymph node metastases suggest that Bcl-2
      does not play a centralrole in pancreatic tumourigenesis and cancer progression.

PMID- 11523053
TI  - Deletion at 3p25.3-p23 is frequently encountered in endocrine pancreatic tumours
      and is associated with metastatic progression.
AB  - For several reasons, chromosome 3p is thought to be involved in the pathogenesis
      of sporadic endocrine pancreatic tumours (EPTs): von Hippel-Lindau's disease (VHL
      gene at 3p25.5) is associated with EPTs; 3p is frequently involved in solid human
      tumours; and comparative genomic hybridization has identified frequent losses at
      3p in EPTs. This study investigated 99 benign and malignant tumours, including 20
      metastases, from 82 patients, by microsatellite loss of heterozygosity (LOH)
      analysis and fluorescence in situ hybridization (FISH) in order to evaluate the
      importance of chromosome 3p deletions in the molecular pathogenesis and
      biological behaviour of EPTs, to elaborate a common region of deletion, and to
      narrow down putative tumour suppressor gene loci. Allelic losses of 3p were found
      in 58/99 (58.6%) of tumours in 45/82 (54.9%) patients; analysis of seven
      microsatellite markers (3p26-p21) revealed a common region of LOH at 3p25.3-p23.
      The LOH frequency was significantly higher in malignant than in benign neoplasms
      (70.2% versus 28.0%; p=0.001). In addition, a strong correlation was found
      between the loss of alleles on chromosome 3p and clinically metastatic disease
      (LOH of 73.7% in metastasizing versus 41.5% in non-metastasizing tumours;
      p=0.008). EPTs from these patients showed a tendency towards losing large parts
      or the entire short arm of chromosome 3 with tumour progression. Furthermore,
      FISH analysis revealed complete loss of chromosome 3 in ten out of 37 EPTs (27%).
      These results indicate that a putative tumour suppressor gene at 3p25.3-p23 may
      play a role in the oncogenesis of sporadic EPTs and that losses of larger
      centromeric regions are associated with metastatic progression.

PMID- 11523054
TI  - In situ detection of telomerase enzymatic activity in human hepatocellular
      carcinogenesis.
AB  - Telomerase enzymatic activity has been detected in most human malignant tumours
      including hepatocellular carcinoma. In order to assess the cellular source, the
      topographic distribution, and the chronology of telomerase re-expression during
      human liver carcinogenesis, an in situ technique derived from the standard TRAP
      (telomeric repeat amplification protocol) assay was set up that allowed the
      detection of telomerase enzyme activity at the cellular level on frozen liver
      tissue sections. In situ TRAP (ISTRAP) was performed on 27 hepatocellular
      carcinomas (HCCs) and 57 non-tumour livers, including normal liver without HCC,
      liver samples adjacent to tumour with and without hepatic cirrhosis, and biopsies
      of chronic hepatitis. In HCC, telomerase was detected in the nuclei of liver
      tumour cells in 23/27 cases (85%), with a heterogeneous distribution within the
      tumour. This signal was also detected in clusters of hepatocytes in 16/26 (61%)
      samples of liver adjacent to HCC, in 10/23 (43%) cases of chronic viral hepatitis
      without adjacent HCC, and in scattered nuclei of 2/8 histologically normal
      livers. Comparison of the results obtained with ISTRAP and standard TRAP assays
      on tissue extracts suggests a gain in sensitivity with the in situ technique.
      This study confirms that telomerase is expressed in most HCCs and suggests that
      focal telomerase reactivation is an early event during human liver
      carcinogenesis. ISTRAP is a sensitive technique that allows the study of
      telomerase expression in the morphological context.

PMID- 11523055
TI  - Expression of Fas and Fas ligand in uveal melanoma: biological implication and
      prognostic value.
AB  - The interaction between Fas and Fas ligand is one possible immune escape
      mechanism used by tumour cells. In the present study, melanoma tissue from 103
      patients who underwent enucleation for malignant uveal melanoma (iris melanomas
      excluded) was stained by immunohistochemistry with monoclonal antibodies specific
      for Fas, Fas ligand, CD3, CD8, and CD68. Histological and clinical data for these
      tumours were assessed. Both Fas and Fas ligand were detected in uveal melanomas.
      Cells of the monocyte/macrophage lineage rather than T-cells were the predominant
      group of tumour-infiltrating cells. The metastasis-free 5-year survival rates in
      the univariate analyses were considerably lower in patients with tumours that
      lacked Fas ligand expression (< 35% of the tumour cells), in the presence of more
      than 50 CD8-positive cells in 20 high-power fields and in the presence of more
      than 100 CD3-positive cells in 20 high-power fields. Fas and Fas ligand
      expression was associated with scleral infiltration. After adjustment for scleral
      infiltration, the predictive value of both Fas and Fas ligand expression was
      markedly decreased. In addition, the CD3- and CD8-positive cell count was
      positively associated with the histological cell type. Cox proportional hazards
      models showed that the presence of CD3- and CD8-positive cells was not an
      independent prognostic factor after adjusting for histological cell type. This
      preliminary observation deserves further investigation, which may shed more light
      on the immune escape mechanisms of this tumour and thus enable novel therapeutic
      strategies. The clinical relevance of this observation is limited, as more
      predictive parameters have been described for uveal melanoma.

PMID- 11523056
TI  - Expression of the Sonic Hedgehog receptor "PATCHED" in basal cell carcinomas and
      odontogenic keratocysts.
AB  - Basal cell carcinoma (BCC) is a common invasive skin lesion in Caucasians.
      Odontogenic keratocysts (OKs) are developmental, non-inflammatory oral cysts.
      They can be sporadic and/or multiple and are locally destructive. Basal cell
      naevus syndrome (BCNS) comprises both multiple BCCs and multiple OKs, in addition
      to several other systemic manifestations. The genetic defect underlying this
      autosomal dominant syndrome is a germ line mutation in the Sonic Hedgehog
      receptor PATCHED (PTCH) gene. For this study, a rabbit anti-peptide PTCH
      antiserum was produced. Immunohistochemistry procedures were performed using PTCH
      antibody and commercially produced GLI-1 antibody (downstream member in the
      hedgehog pathway) to stain 11 BCNS-OKs, eight sporadic OKs, two BCNS-BCCs, and
      six sporadic BCCs. Most of these lesions had been previously screened for PTCH
      mutation. Most BCCs (n=7) demonstrated moderate staining, with the heaviest
      staining in the outer palisading cell layer, except a BCNS-BCC which had mutation
      proximal to the sequence used for production of immunogenic peptide; this
      demonstrated only weak staining. Although moderate to heavy staining with PTCH
      antibody was demonstrated in the epithelium of both types of OK (n=19), a quite
      different pattern of staining of the basal cell layer was observed in the two
      patient groups. In BCNS, OK staining was heaviest in basal epithelial layers. In
      contrast, staining in non-BCNS odontogenic keratocysts was exclusively located in
      the superficial epithelial layers. Up-regulation of PTCH and GLI-1 protein was
      demonstrated in both BCCs and OKs. The pattern of PTCH expression matched the
      PTCH transcript pattern previously reported in BCCs and appeared sufficiently
      characteristic in OKs to allow differentiation between syndromic and non
      syndromic cysts.

PMID- 11523057
TI  - Intrahepatic MxA expression is correlated with interferon-alpha expression in
      chronic and fulminant hepatitis.
AB  - Interferon-alpha (IFN-alpha) has potent pro-inflammatory and anti-viral
      functions. It exerts its effects by inducing intracellular proteins such as MxA.
      To analyse the role of intrahepatic interferon activation, IFN-alpha and MxA
      expression was studied by immunohistochemistry in explant livers of 20 patients
      with fulminant hepatic failure (FHF), 41 patients with chronic liver disease
      (CLD), and ten normal controls (NCs). In NCs only small numbers of Kupffer cells,
      but no hepatocytes, showed IFN-alpha and MxA expression. In contrast,
      significantly enhanced numbers of IFN-alpha- and MxA-positive Kupffer cells,
      along with small numbers of MxA-positive and larger numbers of IFN-alpha-positive
      lymphocytes, were found in CLD and in FHF. MxA protein was also expressed on
      hepatocytes and bile ducts in the vicinity of IFN-alpha-positive inflammatory
      infiltrates (hepatocytes: NCs: 0%, CLD: 8%, FHF: 68%; bile ducts: NCs: 19%, CLD:
      46%, FHF: 83%). A significant correlation was found between the numbers of IFN
      alpha- and MxA-positive cells (r=0.67, p<0.001). Thus, large amounts of IFN-alpha
      are released in the livers of patients with FHF, which is likely to contribute to
      immune-mediated liver cell damage. Intrahepatic MxA expression corresponds to IFN
      alpha produced particularly by infiltrating inflammatory cells, rather than by
      hepatocytes themselves.

PMID- 11523058
TI  - Distribution and activation of eosinophils in inflammatory bowel disease using an
      improved immunohistochemical technique.
AB  - Eosinophils are a recognized feature of inflammatory bowel disease (IBD), but
      their tissue distribution and functional importance in Crohn's disease (CD) and
      ulcerative colitis (UC) remain obscure. This study describes an improved
      immunohistochemical protocol to identify eosinophils in full thickness bowel wall
      specimens of IBD (n=40) and their in situ relationships with the chemoattractants
      eotaxin and RANTES. Eosinophils were identified using immunohistochemistry with a
      combination of monoclonal antibodies (EG1+EG2+MBP), an ultrasensitive technique
      superior to other methodologies, and their tissue distributions were related to
      those for eotaxin, RANTES, mast cells and neutrophils. Increased numbers of
      eosinophils (up to 400 cells/mm(2)) were observed in active, fulminant
      inflammation in both CD and UC, this being related to the severity of
      inflammation and not the diagnosis of the two disorders. The chemoattractants
      eotaxin (CCL11) and RANTES (CCL5) were upregulated in IBD tissues showing
      eosinophilia. Neutrophils and mast cells were commonly associated with eosinophil
      accumulations. Eosinophil numbers and their in situ activation are increased in
      active rather than chronic IBD. The observations strongly suggest a pivotal role
      for the eosinophil and its potent mediators in many pathophysiological symptoms
      of CD and UC, where it represents the major proportion of all granulocytic cells
      in active inflammatory bowel disease.

PMID- 11523059
TI  - Apoptosis induction by sennoside laxatives in man; escape from a protective
      mechanism during chronic sennoside use?
AB  - Chronic sennoside use induces melanosis coli (MC) and possibly increases
      colorectal cancer risk. Sennosides alter colonic crypt length, proliferative
      activity, and bcl-2 expression 18 h after administration. To investigate possible
      mechanisms for carcinogenesis, the effects of acute sennoside use and the
      presence of MC on colorectal epithelium were studied. Colorectal biopsies from 15
      subjects receiving sennosides 6 h before sigmoidoscopy (Sen), 15 controls (NSen),
      and 27 with MC [11 moderate (MMC) and 16 severe (SMC)]. were analysed for degree
      of apoptosis (H&E staining), immunohistochemical p53, p21/WAF and bcl-2
      expression, and proliferative activity (labelling index, LI). Apoptosis
      (p=0.0004), intensity of p53 staining (p=0.01), and p21/WAF expression (p=0.008)
      were increased in Sen and SMC compared with NSen and MMC. p53 expression was
      increased in Sen (p=0.004). No difference in bcl-2 expression or LI was observed.
      Crypts were shorter in Sen (p=0.05) and longer in SMC (p=0.04) than in NSen. It
      is concluded that sennosides acutely induce apoptosis of colonic epithelial
      cells, presumably by a p53, p21/WAF-mediated pathway, resulting in shorter
      crypts. In severe melanosis coli, apoptosis seems to be delayed, causing longer
      crypts without a rise in proliferative activity or bcl-2 expression. This escape
      from a presumably protective mechanism may enhance the risk of carcinogenesis
      during chronic sennoside use.

PMID- 11523060
TI  - Brain Abeta amyloidosis in APPsw mice induces accumulation of presenilin-1 and
      tau.
AB  - APPsw transgenic mice (Tg2576) overproducing mutant amyloid beta protein
      precursor (betaAPP) show substantial brain Abeta amyloidosis and behavioural
      abnormalities. To clarify the subsequent abnormalities, the disappearance of
      neurons and synapses and dystrophic neurite formation with accumulated proteins
      including hyperphosphorylated tau were examined. Tg2576 demonstrated substantial
      giant core plaques and diffuse plaques. The number of neurons was significantly
      decreased in the areas containing the amyloid cores compared with all other areas
      and corresponding areas in non-transgenic littermates in sections visualized by
      Nissl plus Congo red double staining (p<0.001). The presynaptic protein alpha
      synuclein and postsynaptic protein drebrin were also absent in the amyloid cores.
      betaAPP and presenilin-1 were accumulated in dystrophic neurites in and around
      the core plaques. Tau phosphorylated at five independent sites was detected in
      the dystrophic neurites in the amyloid cores. Thus, the giant core plaques
      replaced normal brain tissues and were associated with subsequent pathological
      features such as dystrophic neurites and the appearance of hyperphosphorylated
      tau. These findings suggest a potential role for brain Abeta amyloidosis in the
      induction of secondary pathological steps leading to mental disturbance in
      Alzheimer's disease.

PMID- 11523063
TI  - Improved RP-HPLC determination of quinine in plasma and whole blood stored on
      filter paper.
AB  - Analysis of quinine in plasma and whole blood samples dried on filter paper is
      described. Sample preparation involves liquid extraction of plasma and whole
      blood from the filter paper and subsequent solid-phase extraction using C8 Bond
      Elut cartridges. A reverse-phase liquid chromatography system with UV detection
      and fluorescence detection was used. The analytical characteristics of the method
      are reported, with a quantification limit of 0.1 microg mL(-1) and within an
      assay coefficient of variation of 5.6-8.4% in plasma and 6.5-12% in whole blood.
      Representative chromatograms are shown as a function of time for samples from
      human subjects after ingestion of a single 400-mg dose of quinine sulphate.
      Quinidine, dihydroquinine and metabolites are well separated from quinine with a
      resolution of above 1 (Rs>1).

PMID- 11523062
TI  - Pharmacokinetic assessment of an oral enalapril suspension for use in children.
AB  - The angiotensin-converting enzyme (ACE) inhibitor enalapril is commonly used to
      treat pediatric hypertension. Because some children are unable to swallow tablets
      or require doses less than the lowest available enalapril tablet, an enalapril
      suspension was developed. This study examined the relative bioavailability of
      enalapril suspension (10 mg) (S) compared with 10-mg marketed VASOTEC tablets (T)
      in 16 healthy adult subjects. The geometric mean ratio (S/T) estimate of urinary
      recovery of free enalaprilat, the active moiety, was 0.92 (90% confidence
      interval (CI): 0.80, 1.07). Urinary recovery data indicate that approximately 50%
      of the dose was absorbed (50% recovered in urine as enalapril plus enalaprilat)
      with about 30% of the dose recovered as free enalaprilat for both S and T. The
      geometric mean ratios (S/T) of serum AUC and C(max) were 1.01 (90% CI: 0.90,
      1.13) and 0.98 (90% CI: 0.83, 1.16), respectively. Suspension T(max) was slightly
      shorter (0.5 h) than that for tablet, but this difference is not clinically
      significant. Both formulations were well tolerated and there were no clinically
      significant adverse experiences. We conclude that the bioavailability of
      enalapril oral suspension 10-mg is similar to that of VASOTEC 10-mg tablet.
      Instructions for compounding enalapril are provided.

PMID- 11523064
TI  - Equally potent inhibitors of cholesterol synthesis in human hepatocytes have
      distinguishable effects on different cytochrome P450 enzymes.
AB  - Six 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (the
      present cholesterol-lowering drugs known as statins), lovastatin (L), simvastatin
      (S), pravastatin (P), fluvastatin (F), atorvastatin (A) and cerivastatin (C) are
      shown to be potent inhibitors of cholesterol synthesis in human hepatocytes, the
      target tissue for these drugs in man. All six inhibited in the nM range (IC(50)
      values: 0.2-8.0 nM). As daily used cholesterol-lowering drugs they are likely
      coadministered with other drugs. While several cytochrome P450 (CYP) enzymes are
      involved in drug metabolism in the liver and thus play an important role in drug
      drug interaction it was investigated which of these enzymes are influenced by the
      active forms of the six statins. These enzyme activities were studied in human
      liver microsomal preparations, and in simian and human hepatocytes in primary
      culture. The following CYP reactions were used: nifedipine aromatization
      (CYP3A4), testosterone 6beta-hydroxylation (CYP3A4), tolbutamide
      methylhydroxylation (CYP2C9), S-mephenytoin 4-hydroxylation (CYP2C19), bufuralol
      1'-hydroxylation (CYP2D6), aniline 4-hydroxylation (CYP2E1), coumarin 7
      hydroxylation (CYP2A6) and 7-ethoxyresorufin O-dealkylation (CYP1A1/2). In the
      human liver microsomes the statins (concentrations up to 400 microM) did not
      influence the CYP1A1/2 activity and hardly the CYP2A6 and CYP2E1 activities.
      Except P, the other five statins were stronger inhibitors of the CYP2C19 activity
      with IC(50) values around 200 microM and the same holds for the effect of A, C
      and F on the CYP2D6 activity. L and S were weaker inhibitors of the latter enzyme
      activity, whereas P did not influence both activities. About the same was
      observed for the statin effect on CYP2C9 activity, except that F was a strong
      inhibitor of this activity (IC(50) value: 4 microM). Using the assay of
      testosterone 6beta-hydroxylation the CYP3A4 activity was decreased by L, S and F
      with IC(50) values of about 200 microM and a little more by C and A (IC(50)
      around 100 microM). P had hardly an effect on this activity. To a somewhat less
      extent the same trend was seen when CYP3A4 activity was measured using nifedipine
      as substrate. The inhibitory effects observed in microsomes were verified in
      suspension culture of freshly isolated hepatocytes from Cynomolgus monkey (as a
      readily available model) and of human hepatocytes. In general the same trends
      were seen as in the human microsomes, except that in some cases the inhibition of
      the CYP activity was less, possibly by the induction of the particular CYP enzyme
      by incubation of the cells with a particular statin. F remained a strong
      inhibitor of CYP2C9 activity in human and monkey hepatocytes. A induced the
      CYP2C9 in monkey hepatocytes but was an inhibitor of the CYP2C9 in human
      hepatocytes. A, S, L and C were moderate inhibitors in both cellular systems of
      CYP3A4. P was not affecting any of the CYP activities in the three systems
      studied. It is concluded that different CYP enzymes interact with different
      statins and therefore differences in between these drugs are to be expected when
      drug-drug interaction is considered.

PMID- 11523065
TI  - Stereoselective pharmacokinetics of desbutylhalofantrine, a metabolite of
      halofantrine, in the rat after administration of the racemic metabolite or parent
      drug.
AB  - The main objective of this study was to determine the pharmacokinetics of the
      enantiomers of desbutylhalofantrine (DHF), a metabolite of halofantrine (HF), in
      the rat. Rats received either intravenous (2 mg/kg) or oral (7 mg/kg) (+/-)-DHF
      HCl, or (+/-)-HF HCl intravenously (3 mg/kg). Enantiomer concentrations in plasma
      were determined by a stereospecific assay. In all rats, the plasma concentrations
      of (+)-DHF exceeded those of (-)-DHF. After (+/-)-DHF, the mean (+):(-) ratios of
      AUC(0-infinity) after oral and intravenous dosing were 3.7 and 2.8, respectively.
      After intravenous doses of DHF, the (-):(+) enantiomeric ratios of Cl and V(dss)
      were approximately 2.8. There were no significant differences between the
      enantiomers in t(1/2) (mean 14-23 h) or t(max) (mean 10-12 h) after intravenous
      or oral administration of DHF. Oral bioavailability estimates of DHF enantiomers
      (>59%) were higher than those previously estimated for HF in the rat. The
      stereoselectivity in HF kinetics was not as pronounced as for DHF. It was
      estimated that over 44% of the dose of HF is metabolized to DHF enantiomers. It
      was concluded that DHF possesses a pharmacokinetic profile similar to that of HF,
      each possessing low values of clearance and high volume of distribution. DHF
      differed from HF in its degree of stereoselectivity in pharmacokinetics, and in
      its extent of oral bioavailability.

PMID- 11523067
TI  - Theory and practice in medical statistics.
AB  - The discipline of statistics generally, and that of medical statistics in
      particular, has evolved through two traditions, the theoretical and the
      practical. Their history, traced briefly here, shows recurrent points of contact
      and a process of gradual merging which is now almost complete. However, the
      current tendency to build complex mathematical and computing models may lead to
      over-confidence in their conclusions, when some crucial aspects of the data
      cannot easily be modelled satisfactorily. Illustrations are drawn from the use of
      formal stopping rules in the monitoring of clinical trials, and from the
      treatment of missing data and incomplete compliance with the trial protocol.

PMID- 11523068
TI  - The impact of the international guideline entitled Statistical Principles for
      Clinical Trials (ICH E9).
AB  - At the time of writing, the ICH E9 Note for Guidance entitled "Statistical
      principles for clinical trials" has been in force in Europe, Japan and the U.S.A.
      for almost a year. The purpose of this paper is to review the initial progress of
      E9 in terms of its degree of acceptance and also in terms of any early problems
      which have emerged. A different means of exploring these questions has been
      adopted in each of the three regions. From Europe there is a regulatory
      perspective on statistical issues which have been found to be incompletely
      covered within E9 and which have been important for specific regulatory
      decisions. From the U.S. there is a report of the results of a survey of U.S.
      pharmaceutical industry opinion concerning the effect of E9 on statistical
      practice in drug development. From Japan there is a discussion of the shortage of
      qualified statisticians in Japan and the difficulties that this causes when
      trying to implement E9. Some overall conclusions are drawn.

PMID- 11523069
TI  - Statistical considerations of FDA and CPMP rules for the investigation of new
      anti-bacterial products.
AB  - In this paper I investigate statistical properties of some guidance given by the
      FDA and by the CPMP on the planning, conduct and analysis of clinical trials with
      new anti-bacterial substances using an active control design. It is demonstrated
      that the non-inferiority margin proposed by the FDA has some undesirable
      features, and that the CPMP guidance may need further interpretation with respect
      to a statement that the non-inferiority margin may be smaller than 10 per cent
      for response rates >90 per cent. A new margin is proposed that combines the
      desirable properties from both the FDA and the CPMP guidance. It is also shown
      that the approximate unconditional tests that are in use in such trials are quite
      unreliable with respect to preserving the nominal type I error. Unconditional
      exact tests are presented as a remedy for this issue.

PMID- 11523070
TI  - Independent data monitoring committees: rationale, operations and controversies.
AB  - Data monitoring committees (DMCs) have become an increasingly common component of
      randomized clinical trials in recent years. As experience has accumulated, and
      more individuals and organizations have become involved in such activities, a
      variety of approaches to the operation of such committees has inevitably arisen.
      Because these committees play such a critical role in the process of new drug
      development, it is important to consider the implications of the different
      approaches that are being used. It is also timely to consider the present and
      possible future regulatory status of data monitoring committees. Published in
      2001 by John Wiley & Sons, Ltd.

PMID- 11523071
TI  - Non-parametric analysis of covariance for confirmatory randomized clinical trials
      to evaluate dose-response relationships.
AB  - In confirmatory randomized clinical trials that are designed to compare multiple
      doses of a test treatment with a control group and with one another, there are
      often statistical issues regarding compound hypotheses and multiple comparisons
      which need to be considered. In most cases the analysis plan needs a clear
      specification for the proposed order for conducting statistical tests (or for
      managing the overall significance level), which statistical methods will be used,
      and whether adjustment for covariates will be performed. There are several
      benefits of specifying non-parametric analysis of covariance (ANCOVA) for
      performing the primary confirmatory analyses. Only minimal assumptions are needed
      beyond randomization in the study design, whereas regression model based methods
      have assumptions about model fit for which departures may require modifications
      that are incompatible with a fully prespecified analysis plan. Non-parametric
      methods provide traditionally expected results of ANCOVA; namely, a typically
      small adjustment to the estimate for a treatment comparison (so as to account for
      random imbalance of covariates between treatment groups) and variance reduction
      for this estimate when covariates are strongly correlated with the response of
      interest. The application of non-parametric ANCOVA is illustrated for two
      randomized clinical trials. The first has a (3 x 4) factorial response surface
      design for the comparison of 12 treatments (that is, combinations of three doses
      of one drug and four doses of a second drug) for change in blood pressure; and
      the second example addresses the comparison of three doses of test treatment and
      placebo for time-to-disease progression. This clinical trial has comparisons
      among treatments made for a dichotomous criterion, Wilcoxon rank scores and
      averages of cumulative survival rates. In each example, the non-parametric
      covariance method provides variance reduction relative to its unadjusted
      counterpart.

PMID- 11523073
TI  - Sample size re-estimation: recent developments and practical considerations.
AB  - Interim findings of a clinical trial often will be useful for increasing the
      sample size if necessary to provide the required power against the null
      hypothesis when the alternative hypothesis is true. Strategies for carrying out
      the interim examination that have been described over the past several years
      include "internal pilot studies", blinded interim sample size adjustment and
      conditional power. Simulation studies show that the alternative methods generally
      control the type I error rate satisfactorily, although the power properties are
      more variable. The important issues associated with sample size re-estimation are
      strategic, not numeric. Clearly expressed regulatory preferences suggest that
      methods not requiring unblinding the data before completion of the trial would be
      most appropriate. Extending a trial has its risks. The investigators/patients
      enrolled later in the course of a trial are not necessarily the same as those
      recruited/entered early. Re-activating the enrollment process may be sufficiently
      complicated and expensive to justify enrolling more investigators/patients at the
      outset. Since sample size re-estimation adjusts the sample size on the basis of
      variability while efficacy interim analysis adjusts the sample size based on the
      basis of estimated effect size, both principles can be used in the same trial.
      Sample size re-estimation may not be advisable for trials involving extended
      follow-up of individual patients or, more generally, when the follow-up time is
      long relative to the recruitment time. In such cases, it may be better to
      estimate the sample size conservatively and introduce an interim efficacy
      evaluation.

PMID- 11523072
TI  - Applying sample survey methods to clinical trials data.
AB  - This paper outlines the utility of statistical methods for sample surveys in
      analysing clinical trials data. Sample survey statisticians face a variety of
      complex data analysis issues deriving from the use of multi-stage probability
      sampling from finite populations. One such issue is that of clustering of
      observations at the various stages of sampling. Survey data analysis approaches
      developed to accommodate clustering in the sample design have more general
      application to clinical studies in which repeated measures structures are
      encountered. Situations where these methods are of interest include multi-visit
      studies where responses are observed at two or more time points for each patient,
      multi-period cross-over studies, and epidemiological studies for repeated
      occurrences of adverse events or illnesses. We describe statistical procedures
      for fitting multiple regression models to sample survey data that are more
      effective for repeated measures studies with complicated data structures than the
      more traditional approaches of multivariate repeated measures analysis. In this
      setting, one can specify a primary sampling unit within which repeated measures
      have intraclass correlation. This intraclass correlation is taken into account by
      sample survey regression methods through robust estimates of the standard errors
      of the regression coefficients. Regression estimates are obtained from model
      fitting estimation equations which ignore the correlation structure of the data
      (that is, computing procedures which assume that all observational units are
      independent or are from simple random samples). The analytic approach is
      straightforward to apply with logistic models for dichotomous data, proportional
      odds models for ordinal data, and linear models for continuously scaled data, and
      results are interpretable in terms of population average parameters. Through the
      features summarized here, the sample survey regression methods have many
      similarities to the broader family of methods based on generalized estimating
      equations (GEE). Sample survey methods for the analysis of time-to-event data
      have more recently been developed and implemented in the context of finite
      probability sampling. Given the importance of survival endpoints in late phase
      studies for drug development, these methods have clear utility in the area of
      clinical trials data analysis. A brief overview of methods for sample survey data
      analysis is first provided, followed by motivation for applying these methods to
      clinical trials data. Examples drawn from three clinical studies are provided to
      illustrate survey methods for logistic regression, proportional odds regression
      and proportional hazards regression. Potential problems with the proposed methods
      and ways of addressing them are discussed.

PMID- 11523074
TI  - Sample size recalculation using conditional power.
AB  - The sample size required to achieve a given power at a prespecified absolute
      difference in mean response may depend on one or more nuisance parameters, which
      are usually unknown. Proposed methods for using an internal pilot to recalculate
      the sample size using estimates of these parameters have been well studied. Most
      of these methods ignore the fact that data on the parameter of interest from
      within this internal pilot will contribute towards the value of the final test
      statistic. We propose a method which involves recalculating the target sample
      size by computing the number of further observations required to maintain the
      probability of rejecting the null hypothesis at the end of the study under the
      prespecified absolute difference in mean response conditional on the data
      observed so far. We do this within the framework of a two-group error-spending
      sequential test, modified so as to prevent inflation of the type I error rate.

PMID- 11523075
TI  - The continual reassessment method and its applications: a Bayesian methodology
      for phase I cancer clinical trials.
AB  - We discuss the continual reassessment method (CRM) and its extension with
      practical applications in phase I and I/II cancer clinical trials. The CRM has
      been proposed as an alternative design of a traditional cohort design and its
      essential features are the sequential (continual) selection of a dose level for
      the next patients based on the dose-toxicity relationship and the updating of the
      relationship based on patients' response data using Bayesian calculation. The
      original CRM has been criticized because it often tends to allocate too toxic
      doses to many patients and our proposal for overcoming this practical problem is
      to monitor a posterior density function of the occurrence of the dose limiting
      toxicity (DLT) at each dose level. A simulation study shows that strategies based
      on our proposal allocate a smaller number of patients to doses higher than the
      maximum tolerated dose (MTD) compared with the original method while the mean
      squared error of the probability of the DLT occurrence at the MTD is not
      inflated. We present a couple of extensions of the CRM with real prospective
      applications: (i) monitoring efficacy and toxicity simultaneously in a
      combination phase I/II trial; (ii) combining the idea of pharmacokinetically
      guided dose escalation (PKGDE) and utilization of animal toxicity data in
      determining the prior distribution. A stopping rule based on the idea of
      separation among the DLT density functions is discussed in the first example and
      a strategy for determining the model parameter of the dose-toxicity relationship
      is suggested in the second example.

PMID- 11523076
TI  - Paradigm shifts in clinical trials enabled by information technology.
AB  - The use of the world wide web for clinical trials changes the processes of
      performing clinical research in several fundamental ways. Greatly improved
      security, monitoring capability, and accuracy and timeliness of study conduct can
      be achieved while lowering cost. Data quality is enhanced while co-ordinating
      centre effort is reduced. The web provides a natural environment for linking the
      various components of clinical research, leading to new levels of simplicity and
      efficiency. It also enhances opportunities for recruitment of study investigators
      and patients. Other information technology tools and databases can be used to
      assist in this regard as well. Web-based trials change the relationship of the
      investigator site to the study and the site to the co-ordinating centre.
      Different roles and responsibilities lead to simplified processes and more and
      higher quality data. Many standard co-ordinating centre activities, such as
      randomization, protocol implementation and amending, document tracking, adverse
      event reporting, site monitoring, report generation and data analysis are all
      fundamentally changed in a web-based trial. Opportunities are enhanced to
      identify potential investigators and support their successful study conduct. As
      the role of investigator sites is changed in web-based research, more primary
      care medical providers can be attracted to research, providing more typical
      patients to studies than those sometimes available through more traditional
      research sites, especially those at academic study sites. Other activities can
      now be co-ordinated electronically with the advent of the web. The Institutional
      Review Board (IRB) can use online tools to control investigator participation,
      resulting in improved study efficiency and patient safety. A web-based research
      pharmacy provides tremendous efficiencies in managing and distributing study
      medications. Financial payments to the sites can be performed and recorded
      electronically, or even administered based on timeliness and quality of the data.
      Our early experience with web-based trials indicates that there can be tremendous
      gains in study efficiency and accuracy by restructuring processes, roles and
      responsibilities through a comprehensive centralized, web-based trial. The future
      appears bright for web-based clinical trials.

PMID- 11523077
TI  - Enhancing the value delivered by the statistician throughout drug discovery and
      development: putting statistical science into regulated pharmaceutical
      innovation.
AB  - With the dawn of the 21st century, the pharmaceutical industry faces a
      dramatically different constellation of business and scientific predictors of
      success than those of just a few years ago. Significant advances in science at
      the genetic, molecular and cellular levels, combined with progress demonstrated
      around the globe with drug regulations, have increased business and competitive
      opportunities. This has occurred in search of better and cheaper medicines that
      reach patients with unmet medical needs as quickly as possible. Herein lie new
      opportunities for those who can help business and regulatory leaders make good
      decisions about drug development and market authorization as quickly and
      efficiently as possible in the presence of uncertainty. The statistician is
      uniquely trained and qualified to render such value. We show how the statistician
      can contribute to the process of drug innovation from the very early stages of
      drug discovery until patients, payers and regulators are satisfied. Indeed, the
      very nature of regulated innovation demands that efficient and effective
      processes are implemented which yield the right information for good decision
      making. The statistician can take the lead in setting a strategy that directs
      such processes in the direction of greatest value. This demands skills that
      enable one to identify important sources of variability and uncertainty and then
      leverage those skills to make decisions. If such decisions call for more
      information, then the statistician can render experimental designs which generate
      the right information needed to make the decision in an efficient, timely manner.
      To add value to the enterprise, statisticians will have to become more intimately
      associated with business and regulatory decisions by building on their
      traditional roles (for example, numerical analyst, tactician) and unique skill
      sets (for example, analysis, computation, logical thought and work process,
      precision, accuracy). Business and regulatory savvy, coupled with excellent
      communication and interpersonal skills, will allow statisticians to help create
      the knowledge needed to drive success in the future.

PMID- 11523078
TI  - Exact inference for categorical data: recent advances and continuing
      controversies.
AB  - Methods for exact small-sample analyses with categorical data have been
      increasingly well developed in recent years. A variety of exact methods exist,
      primarily using the approach that eliminates unknown parameters by conditioning
      on their sufficient statistics. In addition, a variety of algorithms now exist
      for implementing the methods. This paper briefly summarizes the exact approaches
      and describes recent developments. Controversy continues about the
      appropriateness of some exact methods, primarily relating to their conservative
      nature because of discreteness. This issue is examined for two simple problems in
      which discreteness can be severe--interval estimation of a proportion and the
      odds ratio. In general, adjusted exact methods based on the mid-P-value seem a
      reasonable way of reducing the severity of this problem.

PMID- 11523079
TI  - Computational tools for exact conditional logistic regression.
AB  - Logistic regression analyses are often challenged by the inability of
      unconditional likelihood-based approximations to yield consistent, valid
      estimates and p-values for model parameters. This can be due to sparseness or
      separability in the data. Conditional logistic regression, though useful in such
      situations, can also be computationally unfeasible when the sample size or number
      of explanatory covariates is large. We review recent developments that allow
      efficient approximate conditional inference, including Monte Carlo sampling and
      saddlepoint approximations. We demonstrate through real examples that these
      methods enable the analysis of significantly larger and more complex data sets.
      We find in this investigation that for these moderately large data sets Monte
      Carlo seems a better alternative, as it provides unbiased estimates of the exact
      results and can be executed in less CPU time than can the single saddlepoint
      approximation. Moreover, the double saddlepoint approximation, while
      computationally the easiest to obtain, offers little practical advantage. It
      produces unreliable results and cannot be computed when a maximum likelihood
      solution does not exist.

PMID- 11523080
TI  - A multiple imputation strategy for incomplete longitudinal data.
AB  - Longitudinal studies are commonly used to study processes of change. Because data
      are collected over time, missing data are pervasive in longitudinal studies, and
      complete ascertainment of all variables is rare. In this paper a new imputation
      strategy for completing longitudinal data sets is proposed. The proposed
      methodology makes use of shrinkage estimators for pooling information across
      geographic entities, and of model averaging for pooling predictions across
      different statistical models. Bayes factors are used to compute weights
      (probabilities) for a set of models considered to be reasonable for at least some
      of the units for which imputations must be produced, imputations are produced by
      draws from the predictive distributions of the missing data, and multiple
      imputations are used to better reflect selected sources of uncertainty in the
      imputation process. The imputation strategy is developed within the context of an
      application to completing incomplete longitudinal variables in the so-called Area
      Resource File. The proposed procedure is compared with several other imputation
      procedures in terms of inferences derived with the imputations, and the proposed
      methodology is demonstrated to provide valid estimates of model parameters when
      the completed data are analysed. Extensions to other missing data problems in
      longitudinal studies are straightforward so long as the missing data mechanism
      can be assumed to be ignorable.

PMID- 11523081
TI  - A method for the analysis of repeated binary outcomes in randomized clinical
      trials with non-compliance.
AB  - When analysing repeated binary data from randomized trials, the model-based
      approaches, such as generalized estimating equations, are frequently used. Such
      methods ignore compliance information and give the model-based intention-to-treat
      estimate of treatment effect. In this paper, the design-based (randomization
      based) semi-parametric estimation procedure is given in the estimation of causal
      risk difference. The resulting risk difference estimator is interpreted as an
      extension of the instrumental variables estimator for a binary outcome which has
      the causal interpretation. Extension of the proposed method to stratified
      analysis is given for data from stratified randomization or meta-analysis. It
      yields a Mantel-Haenszel type risk difference estimator. As a special case of
      stratified analysis, the pattern mixture model which stratifies the data by
      pattern of missing data is performed. Application of the proposed method to a
      trial in which endpoints were the occurrences of fever over three courses is
      provided. The same ideas are applied to the causal risk ratio estimation.

PMID- 11523082
TI  - Some statistical issues in modelling pharmacokinetic data.
AB  - A fundamental assumption underlying pharmacokinetic compartment modelling is that
      each subject has a different individual curve. To some extent this runs counter
      to the statistical principle that similar individuals will have similar curves,
      thus making inferences to a wider population possible. In population
      pharmacokinetics, the compromise is to use random effects. We recommend that such
      models also be used in data rich situations instead of independently fitting
      individual curves. However, the additional information available in such studies
      shows that random effects are often not sufficient; generally, an autoregressive
      process is also required. This has the added advantage that it provides a means
      of tracking each individual, yielding predictions for the next observation. The
      compartment model curve being fitted may also be distorted in other ways. A
      widely held assumption is that most, if not all, pharmacokinetic concentration
      data follow a log-normal distribution. By examples, we show that this is not
      generally true, with the gamma distribution often being more suitable. When
      extreme individuals are present, a heavy-tailed distribution, such as the log
      Cauchy, can often provide more robust results. Finally, other assumptions that
      can distort the results include a direct dependence of the variance, or other
      dispersion parameter, on the mean and setting non-detectable values to some
      arbitrarily small value instead of treating them as censored. By pointing out
      these problems with standard methods of statistical modelling of pharmacokinetic
      data, we hope that commercial software will soon make more flexible and suitable
      models available.

PMID- 11523083
TI  - Statistical issues in bioequivalence [correction of bioequivalance].
AB  - There has been much work recently on individual bioequivalence and the topic has
      attracted considerable controversy. Some previous controversies regarding average
      bioequivalence are examined. It is argued that a contributory factor in these
      controversies may have been confusion over the purpose of bioequivalence trials.
      It is concluded that this purpose needs further clarification before guidelines
      for individual bioequivalence can be established and indeed that such guidelines
      may turn out to be unnecessary.

PMID- 11523084
TI  - An introduction to quadrupole-time-of-flight mass spectrometry.
AB  - A brief introduction is presented to the basic principles and application of a
      quadrupole-time-of-flight (TOF) tandem mass spectrometer. The main features of
      reflecting TOF instruments with orthogonal injection of ions are discussed. Their
      operation and performance are compared with those of triple quadrupoles with
      electrospray ionization and matrix-assisted laser desorption/ionization (MALDI)
      TOF mass spectrometers. Examples and recommendations are provided for all major
      operational modes: mass spectrometry (MS) and tandem MS (MS/MS), precursor ion
      scans and studies of non-covalent complexes. Basic algorithms for liquid
      chromatography/MS/MS automation are discussed and illustrated by two
      applications.

PMID- 11523085
TI  - Analysis of multicomponent mass spectra applying Bayesian probability theory.
AB  - In this paper we develop a method for the decomposition of mass spectra of gas
      mixtures, together with the relevant calibration measurements. The method is
      based on Bayesian probability theory. Given a set of spectra, the algorithm
      returns the relative concentrations and the associated margin of confidence for
      each component of the mixture. In addition to the concentrations, such a data set
      enables the derivation of improved values of the cracking coefficients of all
      contributing species, even for those components for which the set does not
      contain a calibration measurement. This latter feature also allows one to analyze
      mixtures that contain radicals in addition to stable molecules. As an example, we
      analyze and discuss the mass spectra obtained from the pyrolysis of azomethane,
      which contain the radical CH3 apart from nitrogen and C1- and C2-hydrocarbons.

PMID- 11523086
TI  - Gas-phase basicities for ions from bradykinin and its des-arginine analogues.
AB  - Apparent gas-phase basicities (GB(app)s) for [M + H]+ of bradykinin, des-Arg1
      bradykinin and des-Arg9-bradykinin have been assigned by deprotonation reactions
      of [M + 2H]2+ in a Fourier transform ion cyclotron resonance mass spectrometer.
      With a GB(app) of 225.8 +/- 4.2 kcal x mol(-1), bradykinin [M + H]+ is the most
      basic of the ions studied. Ions from des-Arg1-bradykinin and des-Arg9-bradykinin
      have GB(app) values of 222.8 +/- 4.3 kcal x mol(-1) and 214.9 +/- 2.3 kcal x mol(
      1), respectively. One purpose of this work was to determine a suitable reaction
      efficiency 'break point' for assigning GB(app) values to peptide ions using the
      bracketing method. An efficiency value of 0.1 (i.e. approximately 10% of all
      collisions resulting in a deprotonation reaction) was used to assign GB(app)s.
      Support for this criterion is provided by the fact that our GB(app) values for
      des-Arg1-bradykinin and des-Arg9-bradykinin are identical, within experimental
      error, to literature values obtained using a modified kinetic method. However,
      the GB(app)s for bradykinin ions from the two studies differ by 10.3 kcal x mol(
      1). The reason for this is not clear, but may involve conformation differences
      produced by experimental conditions. The results may be influenced by salt-bridge
      conformers and/or by conformational changes caused by the use of a proton-bound
      heterodimer in the kinetic method. Factors affecting the basicities of these
      peptide ions are also discussed, and molecular modeling is used to provide
      information on protonation sites and conformations. The presence of two highly
      basic arginine residues on bradykinin results in its high GB(app), while the
      basicity of des-Arg1-bradykinin ions is increased by the presence of two proline
      residues at the N-terminus. The proline residue in the second position folds the
      peptide chain in a manner that increases intramolecular hydrogen bonding to the
      protonated N-terminal amino group of the proline at the first position.

PMID- 11523087
TI  - Simultaneous determination of all-trans, 9-cis, 13-cis retinoic acid and retinol
      in rat prostate using liquid chromatography-mass spectrometry.
AB  - Since retinoic acid (RA) and RA receptors are key developmental regulators during
      organogenesis, they might participate in the abnormal development of the prostate
      caused by early estrogen exposure. In order to test this assumption, a sensitive
      analytical method that can differentiate 9-cis, 13-cis, and all-trans RA in small
      tissue samples ( approximately 8 mg) is required. Since retinol is the metabolic
      precursor to RA, simultaneous quantification of retinol would also provide
      valuable information. Here, we report a liquid chromatography-mass spectrometry
      method for simultaneous determination of retinol and 9-cis, 13-cis, and all-trans
      RA in rat prostate. Mass spectrometric signal responses for RA were compared
      using positive ion atmospheric-pressure chemical ionization (APCI) and
      electrospray, as well as positive ion and negative ion APCI. Positive ion APCI
      was selected for all subsequent analysis for its better sensitivity, and to
      provide simultaneous determination of retinol and RA. Ventral prostate tissue
      samples were homogenized and extracted following simple protein precipitation
      without derivatization. Baseline separation of 9-cis, 13-cis, and all-trans RA
      standards was obtained by using a non-porous silica C18 column. Selected ion
      monitoring of the ions m/z 301 and m/z 269 was carried out for mass spectrometric
      quantitative analysis. The ion of m/z 301 corresponded to the protonated molecule
      of RA, whereas the ion of m/z 269 corresponded to loss of water or acetic acid
      from the protonated molecule of retinol or the internal standard retinyl acetate
      respectively. The method has a linear response over a concentration range of at
      least three orders of magnitude. The limit of quantitation was determined to be
      702 fmol all-trans RA injected on-column. The method showed excellent intra- and
      inter-assay reproducibility and good recovery, and is suitable for analyzing RA
      and retinol in small tissue samples (approximately 8 mg).

PMID- 11523088
TI  - In vitro immunosuppressive activity of tacrolimus dihydrodiol precursors obtained
      by chemical oxidation and identification of a new metabolite of SDZ-RAD by
      electrospray and electrospray-linked scan mass spectrometry.
AB  - Different tacrolimus epoxides and dihydrodiol epoxides arising from the chemical
      oxidation of the parent drug are described. Open-chain tautomeric forms involving
      the lactone function were identified for the tacrolimus epoxides. Moreover, the
      identification by electrospray and electrospray linked scan mass spectrometry of
      an SDZ-RAD C16-C27 O-demethyl 17, 18-19, 20-21, 22 tris-epoxide new metabolite
      isolated from pig liver microsomes is reported. The in vitro immunosuppressive
      activity, using mixed lymphocyte reactions of the two macrolide reported
      oxidation compounds are discussed.

PMID- 11523089
TI  - Mass spectrometric studies on small open-chain piperazine-containing ligands and
      their transition metal complexes.
AB  - Electrospray ionization Fourier transform ion cyclotron resonance mass
      spectrometry was used to characterize the complexes formed between open-chain
      piperazine-containing ligands and transition metal salts (Cobalt, Copper, Zinc,
      and Cadmium as chlorides, nitrates, and acetates). Only single-charged complexes
      were observed, formed of one ligand (L) and mainly one metal ion (M). Since the
      net charge of the complexes was one, a counterion (X) was attached to some of the
      complexes, with formation of [L + M + X]+ complexes, and a proton was lost from
      others, as in [L - H + M]+ complexes. In most cases the composition of the
      complexes was more dependent on the ligand than the metal salt. Collision-induced
      dissociation measurements showed that complexes with related composition often
      differed in structure, or that interactions between the ligand and the metal ion
      were not alike. The metal ion influenced considerably the fragmentation pathways
      of the ligands, so that the fragmentation products could be used to deduce the
      binding sites of the metal. The variations observed in fragmentation behavior of
      complexes possessing the same ligand but different metal ions can mostly be
      explained by the ionic radius and electronic configuration of the metal ion. The
      results indicated a preference of the piperazine ring of the coordinated ligand
      for the boat conformation.

PMID- 11523090
TI  - Tandem mass spectrum of a farnesyl transferase inhibitor--gas-phase
      rearrangements involving imidazole.
AB  - Compound 1 (1-(3-chlorophenyl)-4-[1-(4-cyanobenzyl)imidazolylmethyl]-2
      piperazinone hydrochloride) is a farnesyl transferase inhibitor intended for
      treatment of cancer. A detailed analysis of the electrospray ionization mass
      spectrometry and tandem mass spectrometry data of protonated 1 shows that in the
      gas phase, upon collision-induced dissociation, this ion undergoes complicated
      rearrangement and fragmentation. These processes include a novel two-step
      rearrangement. The first step involves a gas-phase intramolecular S(N)2 reaction
      that forms an intermediate. The second step consists of three competitive
      rearrangement/fragmentation pathways of the intermediate, giving rise to
      protonated 2, protonated methylene-imidazole, and a distonic methylimidazole
      radical cation. Deuterated 1 was studied under the same experimental conditions,
      and the results strongly support the proposed two-step rearrangement process. It
      is noted that the unique structure of 1, especially the imidazole ring of 1,
      plays a critical role in the rearrangement of protonated 1.

PMID- 11523091
TI  - Probing protein stabilization by glycerol using electrospray mass spectrometry.
AB  - This study shows that electrospray ionization mass spectrometry (ESI-MS),
      combined with a heated turbo ion-spray interface, allows monitoring protein
      stabilization by glycerol in solution. Measurements obtained with the two
      proteins lysozyme and cytochrome c are presented. The observed mass-to-charge
      (m/z) distributions reveal the stabilizing effect of the additive on the protein
      conformations against temperature and acid-induced unfolding, as well as against
      denaturation by acetonitrile. The data obtained with lysozyme allow detection of
      minor conformational changes upon glycerol addition to the native protein, and
      suggest that the protein structure in the presence of the additive is slightly
      compressed compared with its state in water. This result corroborates previous
      evidence obtained by nuclear magnetic resonance. It is also shown that analysis
      of the m/z distributions obtained by ESI-MS can lead to detection of partially
      folded and partially populated states in protein samples.

PMID- 11523092
TI  - Stable isotope dilution negative ion chemical ionization gas chromatography-mass
      spectrometry for the quantitative analysis of paroxetine in human plasma.
AB  - A sensitive and specific method for the quantitative determination of paroxetine
      in human plasma is presented. After solvent extraction from plasma with
      hexane/ethyl acetate (1 : 1) at alkaline pH and derivatization to the
      pentafluorobenzyl carbamate derivative, paroxetine was measured by gas
      chromatography-negative ion chemical ionization mass spectrometry. The
      carboxylate anion at m/z 372 was obtained at high relative abundance. [2H6]
      labeled paroxetine was used as an internal standard and its rapid and facile
      preparation from the unlabeled compound is described. Calibration graphs were
      linear within a range of 0.094-12.000 ng x ml(-1) using 1 ml of plasma and 0.469
      60 ng x ml(-1) using 200 microl of plasma. Intra-day precision was 1.47% (0.375
      ng x ml(-1)), 3.16% (3 ng x ml(-1)) and 1.37% (9 ng x ml(-1)) for the low-level
      method, and 3.37% (1.875 ng x ml(-1)), 2.72% (15 ng x ml(-1)) and 2.22% (45 ng x
      ml(-1)) for the high-level method. Inter-day precision was 1.65% (0.375 ng x ml(
      1)), 2.13% (3 ng x ml(-1)) and 1.66% (9 ng x ml(-1)) for the low-level method,
      and 1.10% (1.875 ng x ml(-1)), 1.56% (15 ng x ml(-1)) and 1.90% (45 ng x ml(-1))
      for the high-level method. At the limit of quantification (0.094 ng x ml(-1)),
      intra-day precision was 4.30% (low-level method) and 2.56% (high-level method),
      and inter-day precision was 3.23% (low-level method) and 3.00% (high-level
      method). The method is rugged, rapid and robust and has been applied to the batch
      analysis of paroxetine during pharmacokinetic profiling of the drug.

PMID- 11523093
TI  - Factors contributing to peak broadening and mass accuracy in the characterization
      of intact spores using matrix-assisted laser desorption/ionization coupled with
      time-of-flight mass spectrometry.
AB  - Factors contributing to peak broadening, accuracy and precision in mass
      assignment in the matrix-assisted laser desorption/ionization characterization of
      a lipopeptide desorbed from intact Bacillus spores were investigated. These
      spores were studied as an example of a thick, topologically irregular sample,
      which present a more difficult target than a pure peptide or protein. The type of
      matrix, matrix:sample ratio, laser fluence, and localized repetitive laser
      irradiation were all found to affect the full-width at half maximum of the
      biomarker. Both in-source and post-source phenomena were shown to contribute.
      Sample thickness had less effect. Precision and accuracy of mass assignment were
      also affected by matrix:sample ratio and laser fluence. In general, this sample
      was responsive to the same experimental variables as pure peptides, and the use
      of an internal standard produced significant improvements in precision and
      accuracy.

PMID- 11523094
TI  - Cross-checking of nanoelectrospray ionization mass spectrometry and computer
      simulation for the evaluation of the interaction strength of non-covalently bound
      enkephalins in solution.
AB  - Nanoelectrospray ionization mass spectrometry (nanoESI-MS) and computer
      simulation were applied to the characterization of non-covalent interactions of
      [Leu5]-enkephalin (LE) and its optical isomers, [D-Tyr1, Leu5]-enkephalin (Y-LE),
      [D-Phe4, Leu5]-enkephalin (F-LE) and [D-Tyr1, D-Phe4, Leu5]-enkephalin (YF-LE).
      The dimer formation tendencies of the optical isomers of LE were evaluated by
      nanoESI-MS using quadruply deuterated LE (H2N-Tyr-(2,2-d2)Gly-(2,2-d2)Gly-Phe-Leu
      COOH, d4-LE) as an internal standard. The relative interaction strengths of the
      optical isomers of LE were estimated to be Y-LE < F-LE < LE < YF-LE. Geometry
      optimization calculations were performed for interactions in vacuo and in water
      using a semi-empirical SCF method (PM3). The initial coordinate of the dimer
      structure of LE was taken from that obtained from single-crystalline x-ray
      diffraction analysis. Estimates of the interaction strengths of the dimer
      complexes were based on the heats of formation of a dimer complex (Hd) and the
      corresponding monomers (Hm) using the equation DeltaH = Hd - 2Hm. The values of
      DeltaH obtained from the calculations for interactions in water decreased in the
      order Y-LE > F-LE > LE > YF-LE. Since the smaller values of DeltaH correspond to
      stronger interactions between peptides, the results from computer simulations
      were qualitatively consistent with those obtained from the nanoESI experiments.
      The possibility of cross-checking these independent techniques was demonstrated
      using medium-sized molecules of biological importance. The agreement of the
      results from the two techniques suggested that nanoESI experiments, at least
      qualitatively, reflected the relative interaction strengths of non-covalently
      bound enkephalins in aqueous solution.

PMID- 11523095
TI  - Identification and characterization by high-performance liquid
      chromatography/electrospray ionization mass spectrometry of a new variant
      hemoglobin, Mataro [beta134(H12) Val > Ala.
AB  - This work illustrates the practical use of combined microbore reversed-phase high
      performance liquid chromatography (RP-HPLC) with electrospray ionization mass
      spectrometry (ESI-MS) in protein identification. The approach consisted of the
      detection of the abnormal beta-globin chain by ESI-MS analysis of mixtures of
      intact globins, which simultaneously provided their molecular masses. Separation
      of the polypeptide globin chains was carried out using microbore C4 RP-HPLC on
      line with ESI-MS. Direct peptide-mapping ESI-MS without previous chromatographic
      separation was performed in order to identify tryptic peptides from whole blood.
      For the sequence confirmation of the abnormal peptide containing the mutation
      point, C18 RP-HPLC tryptic separation of the globin mixture on-line with
      collision-induced dissociation (CID) fragmentation was done. The y series ions
      allowed the identification of the hemoglobin (Hb) variant as [beta134(H12) Val >
      Ala]. This new Hb was named Hb Mataro, after the city where it was detected.

PMID- 11523096
TI  - Gas-phase binding of non-covalent protein complexes between bovine pancreatic
      trypsin inhibitor and its target enzymes studied by electrospray ionization
      tandem mass spectrometry.
AB  - The potential of electrospray ionization (ESI) mass spectrometry (MS) to detect
      non-covalent protein complexes has been demonstrated repeatedly. However,
      questions about correlation of the solution and gas-phase structures of these
      complexes still produce vigorous scientific discussion. Here, we demonstrate the
      evaluation of the gas-phase binding of non-covalent protein complexes formed
      between bovine pancreatic trypsin inhibitor (BPTI) and its target enzymes over a
      wide range of dissociation constants. Non-covalent protein complexes were
      detected by ESI-MS. The abundance of the complex ions in the mass spectra is less
      than expected from the values of the dissociation constants of the complexes in
      solution. Collisionally activated dissociation (CAD) tandem mass spectrometry
      (MS/MS) and a collision model for ion activation were used to evaluate the
      binding of non-covalent complexes in the gas phase. The internal energy required
      to induce dissociation was calculated for three collision gases (Ne, Ar, Kr) over
      a wide range of collision gas pressures and energies using an electrospray
      ionization source. The order of binding energies of the gas-phase ions for non
      covalent protein complexes formed by the ESI source and assessed using CAD-MS/MS
      appears to differ from that of the solution complexes. The implication is that
      solution structure of these complexes was not preserved in the gas phase.

PMID- 11523097
TI  - Structural study on the carbohydrate moiety of calf intestinal alkaline
      phosphatase.
AB  - Surprisingly alkaline phosphatase (AP) (EC 3.1.3.1) of calf intestine is found in
      large amounts, e.g. 80%, within chyme. Most of the enzyme is present as a mixture
      of four differently hydrophobic anchor-bearing forms and only the minor part is
      present as an anchorless enzyme. To investigate whether changes in the N
      glycosylation pattern are signals responsible for large-scale liberation from
      mucosa into chyme, the glycans of the two potential glycosylation sites predicted
      from cDNA were investigated by matrix-assisted laser desorption/ionization and
      electrospray ionization mass spectrometry in combination with exoglycosidase
      treatment after tryptic digestion and reversed-phase chromatography. The glycans
      linked to Asn249 are at least eight different, mainly non-fucosylated,
      biantennary or triantennary structures with a bisecting N-acetylglucosamine. For
      the most abundant glycopeptide (40%) the following glycan structure is proposed:
      [carbostructure: see text]. The glycans linked to Asn410 are a mixture of at
      least nine, mainly tetraantennary, fucosylated structures with a bisecting N
      acetylglucosamine. For the most abundant glycopeptide (35%) the following glycan
      structure is proposed: [carbostructure: see text]. For the structures the linkage
      data were deduced from the reported specificities of the exoglycosidases used and
      the specificities of the transglycosidases active in biosynthesis. The majority
      of glycans are capped by alpha-galactose residues at their non-reducing termini.
      In contrast to the glycans linked to other AP isoenzymes, no sialylation was
      observed. Glycopeptide 'mass fingerprints' of both glycosylation sites and glycan
      contents do not differ between AP from mucosa and chyme. These results suggest
      that the observed large-scale liberation of vesicle-bound
      glycosylphosphatidylinositol (GPI)-anchored AP from mucosa into chyme is unlikely
      to be mediated by alteration of glycan structures of the AP investigated. Rather,
      the exocytotic vesicle formation seems to be mediated by the controlled
      organization of the raft structures embedding GPI-AP. (c) 2001 John Wiley & Sons,
      Ltd.

PMID- 11523099
TI  - Current literature in mass spectrometry.

PMID- 11523098
TI  - Matrix-assisted laser desorption/ionization mass spectrometry analysis of
      fluorophore-labeled oligonucleotides using ferulic acid.

PMID- 11523101
TI  - Nipple aspiration in diagnosis of breast cancer.
AB  - It has been shown that early detection of breast cancer saves lives. Mammography
      and physical examination are currently the most commonly utilized screening
      methods for breast cancer. Research is being carried out to optimize these
      screening methods, as well as to develop new techniques. This review summarizes
      the findings of the research focusing on the diagnostic techniques involving the
      breast ductal system to date. These tests include nipple fluid cytology, nipple
      fluid tumor markers, ductogram, and ductoscopy.

PMID- 11523102
TI  - What every surgical oncologist should know about digital mammography.
AB  - This article reviews the available information on digital mammography for
      surgeons who care for patients with breast cancer. The limitations of the current
      film-based technology and why digital mammography promises to improve breast
      cancer detection and breast lesion diagnosis are described. The basics of digital
      imaging technology are reviewed, including a description of image contrast and
      spatial resolution and its variance from currently available clinical digital
      mammography systems. The results of clinical trials completed to date are
      reported. An upcoming large screening trial for digital mammography, sponsored by
      the National Cancer Institute, is described. Future technological developments,
      including improvements in softcopy display, image processing, computer-aided
      detection and diagnosis (CADD), tomosynthesis, and digital subtraction
      mammography (DSM), are briefly discussed.

PMID- 11523103
TI  - MR imaging: breast cancer staging and screening.
AB  - This review describes the current knowledge and challenges of breast cancer
      staging and screening with MRI of the breast. Assessment of local disease extent,
      including tumor size, multicentricity, and chest wall invasion, can be obtained
      more accurately with MRI than with mammography. Moreover, international experts
      have established standardized reporting of MRI staging results, taking into
      account tumor size measurements and the number of breast quadrants involved.
      Results from MRI assessment of the axilla and skin are promising, but need
      further refinement. Preliminary results of the use of breast MRI in patients at
      high risk for breast cancer demonstrated a superiority of breast MRI over the
      combined use of mammography and high-frequency ultrasound. The role of MRI in
      this subset of patients may be confirmed by ongoing larger multicenter trials.
      Strict protocol conditions are mandatory to maintain a high standard of quality.
      Confirming the nature of "MRI-only" lesions with MRI-guided biopsy systems will
      allow changes in treatment planning. More accurate tumor diagnosis and tumor
      volume evaluation may allow minimally invasive treatment strategies.

PMID- 11523104
TI  - Image-guided breast biopsy.
AB  - Image-guided breast biopsy has become an attractive alternative to wire-localized
      excisional biopsy to evaluate women with nonpalpable abnormalities detected by
      breast imaging. We have organized a database from our institution that includes
      over 3,500 procedures. We have reviewed our institutional results and the
      literature pertaining to image-guided breast biopsy. Discussed in this review are
      the indications and contraindications for image-guided biopsy, common techniques
      employed, accuracy based on pathology, reimbursement issues, and the
      multidisciplinary approach used at our institution. The results of our review
      affirm our position that image-guided breast biopsy is the preferred technique to
      evaluate women with nonpalpable breast imaging abnormalities.

PMID- 11523105
TI  - Intraoperative ultrasound and other techniques to achieve negative margins.
AB  - Over the past few decades new procedures and technologies have been introduced
      into clinical practice for the evaluation and management of breast disease.
      Ultrasound is rapidly becoming a valued tool in the armamentarium of the breast
      surgeon. The use of ultrasound by radiologists and breast surgeons to evaluate
      nonpalpalable detected breast lesions has increased dramatically. With its easy
      portability and improvements in the technology, the use of ultrasound has now
      expanded into the operating room. In this work we review the value of
      intraoperative ultrasound and other techniques in obtaining and assessing margin
      status.

PMID- 11523106
TI  - Techniques of sentinel lymph node biopsy.
AB  - Axillary node status is the single most important prognostic factor for patients
      with primary breast carcinoma. During the last decade, one of the major advances
      in breast cancer has been the development of techniques that make axillary
      staging less morbid and more conservative. The sentinel lymph node (SLN) biopsy
      technique has received much attention as a possible alternative to axillary lymph
      node dissection (ALND). The SLN is defined as the first node in the regional
      lymphatic basin that receives drainage of the primary tumor. We will review the
      different techniques of lymphatic mapping for breast carcinoma, including
      radioactive and/or blue dye indicators, timing and site of injection, and
      preoperative lymphoscintigraphy. The SLN technique involves a multidisciplinary
      team. It is therefore important that each surgeon validate the technique in his
      or her own institution to ensure the successful and accurate assessment of the
      axilla. The SLN technique has modified the surgical management of breast cancer
      patients, although questions as to its safety have yet to be answered.

PMID- 11523107
TI  - Sentinel lymph node--why study it: implications of the B-32 study.
AB  - Surgical removal of the regional lymph nodes by a level I and level II axillary
      dissection remains the standard of care for patients with surgically resectable
      breast cancer. Axillary dissection provides accurate pathologic staging and
      excellent regional disease control, and likely provides a small benefit in
      patient survival. Axillary dissection, however, is associated with significant
      patient morbidity. Sentinel lymph node (SLN) biopsy procedures have been found to
      provide very accurate pathologic staging when compared to axillary dissection;
      however, their effect on regional disease control and patient survival is not yet
      known. The National Cancer Institute (NCI) has sponsored a Phase III prospective,
      randomized clinical trial (the B-32 trial) through the National Adjuvant Breast
      and Bowel Project (NSABP), to compare results of patients treated with SLN biopsy
      alone vs. SLN biopsy with completion axillary node dissection in patients with
      clinically node-negative breast cancer. Results of this trial will provide
      evidence of the safety of SLN biopsy procedures in the management of patients
      with breast cancer.

PMID- 11523108
TI  - Observation of the breast cancer patient with a tumor-positive sentinel node:
      implications of the ACOSOG Z0011 trial.
AB  - Axillary lymph node status has been the most important prognostic factor for
      breast cancer throughout the past century. During the past decade, intraoperative
      lymphatic mapping with sentinel lymph node dissection (SLND) has been
      investigated as an alternative staging modality. This technique may be as
      accurate as ALND, and certainly is less invasive. Adjuvant treatment
      recommendations, which historically were made on the basis of lymph node status
      alone, now take into account primary tumor features, molecular markers, and
      patient characteristics. This evolution of current treatment patterns is driven
      in part by the diminishing size of tumors, the simultaneous decrease in the
      presence of axillary metastases, and a better understanding of tumor-specific
      risk factors. How do these trends affect the interpretation of a tumor-positive
      sentinel node (SN)? Can an axilla with a positive SN be observed? Should it be
      observed? This review examines the implications of a positive SN in the context
      of smaller tumor size, decreased nodal disease, and increased reliance on
      alternative prognostic factors for treatment decisions. The historical data
      comparing ALND to no ALND in clinically node-negative patients is reviewed and
      discussed in the context of observation for a positive SN. These are the issues
      underlying the ACOSOG Z0010 and Z0011 trials.

PMID- 11523109
TI  - Pathologic analysis of sentinel lymph nodes.
AB  - The sentinel lymph node (SLN) procedure enables selective targeting of the first
      draining lymph node, where the initial metastases will form. A negative SLN
      predicts the absence of tumor metastases in the other regional lymph nodes with a
      high degree of accuracy. This means that in case of a negative SLN, regional
      lymph node dissection is no longer necessary. Besides saving patients the
      significant morbidity associated with lymph node dissection, it will also save
      costs. Crucial for the success of the SLN procedure is the screening of the SLN
      for metastases by the pathologist. To this end, several techniques are available
      such as standard histo- and cytopathological techniques, immunohistochemistry,
      flow cytometry, and molecular biological techniques. In this paper, the value of
      these methods for detecting SLN metastases is discussed. Some of these techniques
      have also appeared to be quite useful for intraoperative evaluation of SLNs. The
      standard protocol for detection of SLN metastases consists of extensive
      histopathological investigation including stepped sections stained with
      hematoxylin and eosin (HE) and immunohistochemistry. Intraoperative frozen
      section analysis and imprint cytology of SLNs have been shown to be reasonably
      reliable for detecting breast cancer metastases in SLNs. Further studies are
      necessary to establish the role of multiparameter flow cytometry and
      sophisticated molecular biological techniques such as reverse transcription
      polymerase chain reaction (RT-PCR) in detecting SLN metastases.

PMID- 11523110
TI  - Minimally invasive techniques in breast cancer treatment.
AB  - Breast conservation therapy has largely replaced mastectomy as the surgical
      treatment of choice for early-stage breast cancer. As the sentinel lymph node
      mapping procedure, rather than routine axillary node dissection, becomes the
      standard of care, the next challenge is how to treat the primary tumor without
      surgery. Minimally invasive ablation of the primary tumor is possible with a
      variety of approaches; the goal is to either excise the tumor percutaneously or
      cool it (with cryotherapy) or heat it (with radiofrequency ablation (RFA),
      focused ultrasound, or laser interstitial therapy) sufficiently to cause complete
      cell death. These developing technologies may provide treatment options that are
      psychologically and cosmetically more acceptable to the patient than traditional
      therapies, but they need further investigation to prove that they are
      oncologically sound. This new frontier of surgery without scalpels will require
      surgeons to develop radiologic expertise and to acquire a basic understanding of
      molecular biology.

PMID- 11523111
TI  - Reconstruction of urinary tract utilizing transverse colon conduit for a
      cystectomized patient with post-ureterocutaneostomy complications and sigmoid
      colon cancer.
AB  - A seventy-four years old man had been suffering from symptomatic and infectious
      complications associated with conjoined cutaneoureterostomy following the radical
      cystectomy for advanced transitional cell carcinoma of the bladder 3 years ago.
      He underwent urinary reconstruction using transverse colon conduit after
      diagnostic exclusion of recurrent urothelial tumor in the upper urinary tract,
      evaluation of performance status and endoscopic examination of the colon.
      Enteroscopy incidentally revealed he had an early stage adenocarcinoma in his
      sigmoid colon to be resected, and the resection was followed by the urinary
      diversion. Postoperatively he is satisfied to be free from urinary complications
      and frequently visits the outpatient clinic for painful and troublesome ureteral
      catheter exchange.

PMID- 11523112
TI  - [Cloning and characterization of a novel human cancer/testis-associated gene].

PMID- 11523113
TI  - [The role of macrophage migration inhibitory factor (MIF) for dextran sulfate
      sodium-induced colitis in mice].

PMID- 11523114
TI  - [Enhanced complement sensitivity of NK-T cells in the thymus and spleen and the
      possible mechanism].

PMID- 11523115
TI  - [Overexpression of the human HOXD3-antisense in melanoma cells results in
      decreased invasive activity].

PMID- 11523116
TI  - [Effect of CTLA4Ig gene transfer with adenovirus vector on allogeneic renal graft
      survival in the rat].

PMID- 11523117
TI  - [Gelsolin gene therapy using adenovirus vector for orthotopically implanted human
      urinary bladder carcinoma in nude mice].

PMID- 11523119
TI  - [Positron emission tomography (PET) study of the alterations in brain
      pharmacokinetics of methamphetamine in methamphetamine sensitized animals].
AB  - I investigated the differences in brain pharmacokinetics of [11C]methamphetamine
      ([11C]MAP) in normal and MAP sensitized animals using positron emission
      tomography (PET). [11C]MAP was synthesized by an automated on-line
      [11C]methylation system. I newly produced MAP sensitized dog and monkey by
      repeated MAP treatment. The maximal level of accumulation of [11C]MAP in the
      sensitized dog brain was 1.4 times higher than that in the control. This result
      suggests the changes in the pharmacokinetic profile of MAP in the brain affect
      the development or expression of MAP-induced behavioral sensitization. However,
      the overaccumulation of [11C]MAP in the sensitized monkey brain was not observed
      due to the influence of anesthesia.

PMID- 11523118
TI  - [Development of new synthetic reagents in Mitsunobu-type reaction].
AB  - The author's work in the past 10 years have been reviewed, focusing on their
      endeavor to find more effective and versatile reagents applicable to the
      Mitsunobu-type reactions. The project was originally planned to provide various N
      alkyl-N-allylacylamides, the substrates for the aza-Claisen rearrangement the
      authors have developed. The effort was rewarded by more colorful results than
      expected originally, introducing to the chemical community two new series of
      reagents, that is, azodicarboxamides, such as TMAD and DHTD, and phosphoranes,
      such as CMBP and CMMP. The former series mediates the Mitsunobu reaction between
      primary alcohols and various protonic acids (N- and C-nucleophiles) of pKa up to
      12, while the later, though needed a higher temperature, mediates the reactions
      of both primary and secondary alcohols with protonic acids of pKa of up to 23.5.
      Utilizing both the aza-Claisen rearrangement and new Mitsunobu reaction, a
      variety of natural products including isoirridomyrmecin, alpha-skytanthine,
      antimycin A3b as well as various alkaloids and pheromones were synthesized in
      reasonable ease.

PMID- 11523120
TI  - [Efficient gene delivery into dendritic cells by fiber-mutant adenovirus
      vectors].
AB  - Dendritic cells (DC) are professional antigen-presenting cells with a key
      function in the immune system as initiators of T-cell responses against microbial
      pathogens and tumors. Therefore, the immunization using DC loaded with tumor
      associated antigens is potential to represent a powerful method of inducing anti
      tumor immunity. Recent studies have demonstrated the usefulness of DC genetically
      modified by adenovirus vectors (Ad) to immunotherapy, while sufficient gene
      transduction into DC is required for high doses of Ad. Entry of Ad into target
      cells occurs by serial two steps: the binding of Ad-fiber knob to Coxsackie
      adenovirus receptor (CAR) on the cell surface, and the subsequent interaction
      between Arg-Gly-Asp (RGD) motif located in Ad-penton base and alpha v-integrins.
      The reverse transcription-polymerase chain reaction analysis revealed that the
      relative resistance of DC to Ad-mediated gene transfer was due to the absence of
      CAR expression, and that DC expressed adequate alpha v-integrins. Therefore, we
      investigated whether fiber-mutant Ad (FM-Ad) containing the RGD sequence in the
      fiber knob can efficiently transduce and express high levels of the foreign gene
      into DC. The gene delivery by FM-Ad was more efficient than that by conventional
      Ad in both murine DC lines and normal human DC. Furthermore, both antigen
      presentations via major histocompatibility complex class I molecules and in vivo
      antigen-specific cytotoxic T lymphocyte induction by DC transduced with antigen
      gene by FM-Ad were superior to those by DC applied with conventional AD. We
      propose that alpha v-integrin-targeted FM-Ad is a very powerful tool to implement
      DC-based vaccination strategies.

PMID- 11523121
TI  - [Synthesis and characterization of model system in biological related function-
      model compounds for investigation of metal-metal interaction and nucleobase
      aromatics interaction].
AB  - Several kinds of compounds available as model systems to investigation on metal
      metal interaction in metalloproteins and on interaction of aromatics with
      nucleobases in arene intercalation to DNA were synthesized and characterized by
      spectrometry. Double and triple layered porphyrinophanes linked with 1,1'- or 1,3
      disubstituted ferrocene moieties and their iron and cobalt complexes were
      prepared. Stabilities of their oxygenation complexes depended on bridging mode,
      lengths of alkyl linkers, distance between metals, and feature of hydrophobic
      cavity. Ferrocenophane derivatives in which nucleobase and aromatic hydrocarbon
      (naphthalene or anthracene) moieties substituted to their cyclopentadienyl rings
      in a stacking mode between the two chromophores were synthesized, as a model
      system of intercalation of aromatic condensed-ring hydrocarbons to DNA.
      Characterization of the ferrocenophanes by spectrometry and molecular modeling
      suggested that these chromophores interacted due to NH-pi hydrogen bonding and pi
      pi charge transfer. A number of porphyrin derivatives covalently connected with a
      nucleobase or a nucleobase pair in a face-to-face mode between the porphyrin and
      nucleobase moiety were synthesized. The spectroscopic behavior of the derivatives
      indicate a greater affinity of the guanine-cytosine pair for porphyrin in
      comparison with the adenine-thymine pair. These results are compatible with the
      already reported spectroscopic and kinetic properties of mixing system of DNA and
      porphyrin derivatives. Moreover, the fluorescence spectra of the nucleobase
      porphyrin derivatives gave a piece of evidence to cause DNA cleavage by
      photosensitizer via "type I" mechanism, in which direct action of singlet or
      triplet state of photosensitizer excited by laser irradiation brings about damage
      of cell or DNA.

PMID- 11523122
TI  - [Examination of factors affecting efficacy and adverse effect, for the
      retrospective study of vancomycin hydrochloride (VCM)].
AB  - Vancomycin hydrochloride (VCM) is widely used for treatment of methicillin
      resistant Staphylococcus aureus (MRSA) infections. However, this drug can cause
      sever adverse reactions, such as red neck syndrome, nephrotoxicity and
      ototoxicity. Thus, therapeutic drug monitoring (TDM) was bringing into effect for
      well effectiveness and to prevent side effects. In Kanto Medical Center NTT EC,
      TDM of VCM has been brought into effect since 1994. The date were accumulated
      from 200 patients. In this study, the retrospective research was carried out
      based on 117 cases selected from the above accumulated data, and then several
      factors such as VCM inducing side effect, a therapeutic effect, and the forecast
      of pharmacokinetic parameter using laboratory data were examined. Consequently,
      the high blood concentration trough level, the high value after 1 to 2 hours
      infusion, and the extension of t1/2 were brought forward as a nephrotoxicity
      causing factor, and more over each laboratory data (BUN, Cr, GOT, GPT, gamma-GTP,
      T-BiL, ALP, LDH) was high before infusion of VCM in patients with renal
      dysfunction. High value T-Bil and lower value TP were brought forward in patients
      with hepatic dysfunction, and high eosinophils and high blood concentration were
      brought forward after 1 or 2 hours infusion. In relation to side effects, it was
      found that the outbreak rate of side effects is high in patients with a
      complication of hypertension or diabetes. The administration term was considered
      as a factor which influences the therapeutic effects. The unchanged effect was
      10.9 +/- 7.9 days, the improved effect was 14.6 +/- 9.3 days, the remarkably
      improved effect was 17.7 +/- 14.1 days. As the administration term gets longer,
      the improvement rate was recognized to be an upward tendency. The difference in
      significant effects was recognized between unchanged and remarkably unchanged (p
      < 0.05) effects. As the forecast of pharmacokinetic parameter using the
      laboratory data, VCMt1/2 showed a significant correlation between Cr and T-BiL,
      and it was VCMt1/2 = 8.56CR + 2.169T-Bil + 7.1. This result shows that VCMt1/2
      can be estimated.

PMID- 11523123
TI  - [Efficiency improvement of dispensing of drugs for injection by a total automatic
      injection dispenser system including infusion fluids and its evaluation].
AB  - For the appropriate use of drugs for injection, injection dispensing by
      pharmacists has been initiated at various institutions. With this movement,
      automatic injection dispensers have actively been developed. In our hospital, an
      injection order system was connected with an automatic injection dispenser in
      November, 1997, and this integrated system has been operating in all wards.
      However, the efficiency of dispensing work was not satisfactory because there
      were limitations in the types and volume of drugs placed in the automatic
      injection dispenser. Therefore, we constructed an automatic injection dispenser
      system that allows us to use more than 100 ml infusion fluids and also to use
      drugs stored in a cool place, which could not be used in the conventional system.
      In the new system, two trays coming from an ampoulevial line and an infusion
      fluid line are automatically coordinated using a discharge lifter for each
      patient and transported into an injection cart. After the introduction of this
      system, the automatic dispenser utilization rate in terms of the number of used
      injections increased from 52.6% to 73.3%. In addition, since the dispensing time
      for infusion fluids and drugs stored in a cool place, which had been collected by
      man power, was reduced, it became possible to pay more attention to checking for
      prescription.

PMID- 11523124
TI  - [Establishment of an optimum bowel preparation method before gynecologic
      laparoscopic surgery].
AB  - OBJECTIVE: To establish a new method for preoperative bowel preparation that
      facilitates nursing care and minimizes the patient's discomfort during the
      clinical pathway of laparoscopic surgery. METHOD: A randomized controlled trial
      was conducted for the following two preparation methods. Twenty cases were
      assessed with Method 1 and 18 cases with Method 2. Method 1 (the conventional
      procedure): oral magnesium citrate is given in the afternoon of the day before
      surgery, followed by a glycerin enema in the night of the day before surgery and
      in the morning of the day of surgery. Method 2 (a new procedure): oral magnesium
      citrate is given in the afternoon of the day before surgery, followed by oral
      picosulfate in the night before the day of surgery and a bisacodyl suppository in
      the morning of the day of surgery. To evaluate the two methods we sent
      questionnaires to the surgeons (blinded to the method used), nurses, and
      patients. RESULTS: No statistical difference existed between the two methods in
      their effectiveness as a preoperative treatment. Facilitation of nursing care was
      significantly better in Method 2, and patients had considerably reduced
      discomfort with Method 2. DISCUSSION: Patients who received oral picosulfate and
      a bisacodyl suppository experienced much less discomfort and nursing care was
      easier when compared with the conventional method of administering a glycerin
      enema. Since an enema is disliked by young women and an effect comes out with
      discomfort very shortly after the administration, the degree of discomfort of
      patients would have become high. Picosulfate is an oral medicine and thereby the
      effect comes out mildly. That would be the reason why the degree of discomfort of
      patients was low. In the nursing care, an enema requires time for preparation and
      administration, while picosulfate is easy to administer, making the nursing care
      easier. Therefore, Method 2 was chosen as a preoperative bowel treatment for the
      clinical pathway. Thus, we could establish a new evidence-based method useful for
      the preoperative bowel preparation in the clinical pathway of laparoscopic
      surgery.

PMID- 11523125
TI  - Augmentation of the pharmacological action of corydalis tuber by saussurea root
      in isolated mouse ileum.
AB  - To understand the meaning of blending crude drugs in Chinese medicinal
      prescriptions, the influence of Saussurea root on the pharmacological action of
      Corydalis tuber was examined. Saussurea root increased the depression of
      acetylcholine-induced contraction caused by the hot water extract solution of
      Corydalis tuber in mouse ileum at low dosage, which showed no direct influence on
      acetylcholine. Dehydrocostuslactone in Saussurea root was characterized as the
      component having increasing activity and the relationship between the
      concentration of acetylcholine and the variation in the contraction depressed by
      Corydalis tuber alone or a mixture of the Corydalis tuber and
      dehydrocostuslactone was investigated for clarification of the mode of action.

PMID- 11523126
TI  - Supracostal approach--an excellent exposure for renal and adrenal surgery.
AB  - The supracostal extraperitoneal and extrapleural approach provides wide exposure
      during renal and adrenal operations without damaging the neurovascular bundles
      and spares the partial resection of rib. We performed renal and adrenal
      operations on 33 patients by this approach. The procedures were accomplished
      smoothly obtaining a broad surgical field without costal resection. Complications
      were rare and postoperative pain seemed to be mild. Hence, the supracostal
      approach is considered as a better method with excellent exposure to the kidney
      and adrenal and is anatomically comprehensive.

PMID- 11523127
TI  - Long-term results of neoadjuvant hormonal therapy prior to radical prostatectomy
      in patients with clinically localized prostate cancer: biochemical and
      pathological effects.
AB  - The objective of this study was to evaluate the long-term biochemical and
      pathological effects induced by neoadjuvant hormonal therapy (NHT) in patients
      with clinically localized disease. Between March 1993 and May 1997, 24 patients
      with clinically localized prostate cancer received NHT for 3 to 11 months
      (median: 5 months) using luteinizing hormone-releasing hormone analogue prior to
      radical prostatectomy and pelvic lymphadenectomy. The clinical stage was T1 in 1
      patient, T2 in 17 and T3 in 6, the pretreatment serum prostate-specific antigen
      (PSA) value was < or = 10 ng/ml in 5 patients, 10 to 20 ng/ml in 4 and > 20 ng/ml
      in 15 (mean: 34.7 micrograms/l), and the Gleason score was < or = 4 in 9
      patients, 5 to 7 in 11 and > 8 in 3. The mean prostate specific antigen (PSA)
      value 3 months after NHT had reduced below 2 ng/ml in 18 of the 24 patients
      (67%), and finally decreased by an average of 95% (i.e., 1.9 ng/ml) prior to
      surgery. The pathological stage was pT0 in 2 patients, pT2 in 10 and pT3 in 12.
      The incidence of organ-confined disease (OCD) was significantly higher in
      patients with clinical stage T1 or T2a than with T2b or T3, with pretreatment PSA
      values < or = 10 ng/ml than with PSA values > 10 ng/ml, and with PSA values < or
      = 2 than with PSA values > 2 at 3 months after NHT; in contrast, the Gleason
      score had no significant impact on the rate of OCD. After a median follow-up of
      49 months (range 34 to 85 months), 6 patients (25%) had a recurrence evidenced by
      rising PSA, and the 3-year recurrence-free survival rate was 79%. These results
      suggest that NHT appears not to be of significant additional benefit to patients
      who have a higher clinical T stage, higher pretreatment PSA values and/or in
      patients whose PSA values do not normalize early in the treatment process.

PMID- 11523128
TI  - [Effects of cernitin pollen-extract (Cernilton) on inflammatory cytokines in sex
      hormone-induced nonbacterial prostatitis rats].
AB  - Cernitin pollen-extract (Cernilton, CN) is a preparation made from eight kinds of
      pollen and has been used for various prostatic diseases in Japan and Europe. We
      reported previously that CN possessed a recovery action on the sex-hormone
      induced nonbacterial prostatitis in rats. To clarify the possible mechanism of
      action of CN, we investigated the effects of CN on inflammatory cytokines (IL-1
      beta, IL-6 and TNF-alpha) in the same model. Aged Wistar rats were castrated and
      injected 17 beta-estradiol (0.25 mg/kg/day, s.c.) for 30 days. CN (630 and 1,260
      mg/kg, p.o.) or testosterone (2.5 mg/kg, s.c.) was administered for the last 14
      days of the treatment of 17 beta-estradiol. In control rats, prostatic IL-6 and
      TNF-alpha contents were increased approximately 2-3 fold, and acinar glandular
      inflammation and stromal proliferation were found histopathologically, as
      compared with those of intact rats. On the other hand, CN decreased the increased
      contents of cytokines in a dose-dependent manner. The histopathological changes
      mentioned above were restored in rats treated with 1,260 mg/kg. Testosterone also
      ameliorated them significantly. These results indicate that CN has an anti
      inflammatory action, and that the inhibitory effect of CN on the prostatic
      inflammatory cytokine is an important factor in its action.

PMID- 11523129
TI  - [Serum CA19-9 levels in testicular germ cell tumor patients].
AB  - This study was designed to examine whether measurement of serum CA19-9 was useful
      in testicular germ cell tumor patients. We analyzed the clinical courses of 55
      testicular germ cell tumor cases diagnosed after high orchiectomy. The patients
      in this study consisted of 33 seminomas and 22 non-seminomatous germ cell tumors
      (NSGCT), and their mean age was 32.7 +/- 12.7 years (mean +/- SD). The mean
      follow-up period after the operation was 33.7 months. The positive rate of the
      pre-treatment serum CA19-9 level was 16.4% (3.0% in seminomas versus 36.4% in
      NSGCT, p = 0.0017). The pre-treatment serum CA19-9 levels in NSGCT patients were
      significantly higher than those in seminoma patients (46.6 +/- 50.0 U/ml versus
      10.6 +/- 9.6 U/ml, p = 0.0008). We divided the patients into two groups according
      to the detailed histological types, and found that the serum CA19-9 levels in the
      patients with embryonal carcinoma (EC) were significantly higher than in those
      without EC (p = 0.0160), and the levels in those with yolk sac tumor (YS) were
      higher than in those without YS (p = 0.0099). Moreover, the levels in those with
      either EC or YS were significantly higher than in those with neither EC nor YS (p
      = 0.0004). In 9 patients with a high serum pre-treatment CA19-9 level, the serum
      CA19-9 level was useful as a monitoring marker through the treatment or tumor
      progression. On the other hand, the pre-treatment serum CA19-9 level did not
      correlate with the clinical stage or prognosis. In conclusion, the phenomenon
      that the serum levels of CA19-9 increase in testicular germ cell tumor patients
      is not extremely rare, and in NSGCT, especially in EC or YS, the serum CA19-9 can
      be a useful tumor marker.

PMID- 11523130
TI  - [A case of retroperitoneal ancient schwannoma in the pelvis].
AB  - We treated a case of retroperitoneal ancient schwannoma in the pelvis detected
      incidentally at a health examination without clinical manifestation in a 59-year
      old Japanese man found to have hypertension. Computed tomography showed a
      heterogeneously enhanced 8 x 7 cm solid mass in the pelvic retroperitoneal space.
      Magnetic resonance imaging revealed an encapsulated tumor, showing a low
      intensity on the T1-weighted image, heterogeneously high intensity on the T2
      weighted image and the tumor homogeneously enhanced with Gd-DTPA. It was
      suspected to be a mesenchymal tumor. The tumor was resected en bloc. The
      histologic examination of the extirpated tumor was an ancient schwannoma. A total
      of 11 retroperitoneal ancient schwannoma cases were reviewed.

PMID- 11523131
TI  - [A case of renal cell carcinoma producing alpha-fetoprotein].
AB  - Renal cell carcinoma (RCC) producing alpha-fetoprotein (AFP) is a rare condition
      with only 11 cases reported in Japan to our knowledge. A 69-year-old man was
      admitted to our hospital for further examination of an incidental right renal
      tumor. Laboratory tests showed markedly increased serum level of AFP whereas both
      HBs antigen and anti-HCV antibody were negative. Computed tomography and magnetic
      resonance imaging imagings showed a right renal tumor but no tumor in liver,
      testis or lymph node. We performed right radical nephrectomy. Serum level of AFP
      declined within the normal range 7 weeks after nephrectomy according to its half
      life curve. The tumor specimen was composed mainly of granular cells.
      Immunohistochemical examination of the tumor cells proved the presence of AFP in
      the cytoplasm. The possibility of AFP as a tumor marker of renal cell carcinoma
      in this case was presented.

PMID- 11523132
TI  - [A case of enucleation for multiple renal cell carcinomas in unilateral kidney
      with microwave tissue coagulator].
AB  - A 67-year-old man, who had undergone left nephroureterectomy for ureteral tumor
      (transitional cell carcinoma, G1) eight years previously, was found to have two
      renal tumors in the residual right kidney by the follow-up computed tomography
      (CT). We performed non-ischemic enucleation for multiple tumors at the upper and
      lower pole in the unilateral kidney using a microwave tissue coagulator (MTC). We
      confirmed by means of ultrasonography during operation the absence of any other
      satellite tumors. The operation time was 154 minutes and bleeding during
      operation was 267 ml. There was no difference between creatinine before (0.73
      mg/dl) and after (0.79 mg/dl) operation. On the follow-up CT, there was a low
      density area after enucleation. This area gradually decreased and disappeared on
      enhanced CT 18 months after operation. We enucleated multiple renal cell
      carcinomas using MTC without reduction of renal function or remarkable side
      effects. These results suggested that non-ischemic enucleation using MTC would be
      useful for multiple renal cell carcinoma in the unilateral kidney.

PMID- 11523133
TI  - [A case of Bellini duct carcinoma producing granulocyte colony-stimulating factor
      (G-CSF)].
AB  - A case of Bellini duct carcinoma producing granulocyte colony-stimulating factor
      (G-CSF) is reported. The patient was a 75-year-old female with the chief
      complaint of appetite loss. Abdominal ultrasonography and abdominal computed
      tomography revealed left renal pelvic tumor. Left radical nephrouretrectomy was
      performed. The histopathological report showed Bellini duct carcinoma.
      Immunohistochemical staining using the anti-G-CSF antibody showed positive
      staining in the cancer cells. Preoperatively, the white blood cell count and
      serum G-CSF concentration were elevated to 34,100/microliter and 334 pg/ml
      respectively. After operation these values became normal. However, these values
      were elevated again and CT scan revealed a left pulmonary metastasis 3 months
      after the operation. In spite of chemotherapy, she died of brain metastases 7
      months after the operation.

PMID- 11523134
TI  - [Renal metastasis originating from pulmonary carcinoma: a case report].
AB  - A 61-year-old woman, who had undergone total right pneumonectomy 22 months before
      due to lung cancer (adenosquamous cell carcinoma) was admitted for macroscopic
      hematuria. Abdominal CT showed two renal tumors in the right kidney. Right
      radical nephrectomy was performed, because no imaging study showed any other
      metastasis. Pathological examination revealed adenosquamous cell carcinoma, which
      was the same pathology as the lung cancer had been. She died of the left lung
      metastasis 24 months after right radical nephrectomy. Her prognosis was thought
      to have been prolonged by the operation of right radical nephrectomy.

PMID- 11523135
TI  - [Cadaveric renal transplantation for Goodpasture's syndrome: a case report].
AB  - A 19-year-old man with a history of histologically-proven Goodpasture's syndrome
      (hemoptysis, rapidly progressive glomerulonephritis, and positive anti-glomerular
      basement membrane (anti-GBM) antibody) was maintained on hemodialysis for 21
      months. After steroid pulse therapy and plasmapheresis, his anti-GBM antibody
      disappeared. His stable condition on dialysis and a session of plasmapheresis
      prior to surgery allowed him to undergo cadaveric renal transplantation from a 34
      year-old man. The blood type was identical (group A and Rh (+)), and there was 1
      and 0 mismatch of HLA class 1 and 2, respectively. The initial immunosuppressants
      included cyclosporine, methylprednisolone, mizoribine, azathioprine, and anti
      lymphocyte globulin (ALG). The transplanted kidney regained function on day 6 and
      he was free from hemodialysis. Circulating anti-GBM antibody was negative after
      surgery. The graft has functioned well for almost 4 years after transplantation
      without any episodes of renal or pulmonary complications. To the best of our
      knowledge, this is the first report of renal transplantation for Goodpasture's
      syndrome in the Japanese literature.

PMID- 11523136
TI  - [A case of infected urachal cyst successfully drained by a catheter perforating
      the bladder].
AB  - A 42-year-old man complained of lower abdominal pain. Computed tomographic scan
      and magnetic resonance imaging revealed an infected urachal cyst. A drainage
      catheter, which had multiple holes over a 10 cm length from the catheter tip, was
      placed in the urachal cyst. The catheter was inserted from the subumbilicus
      region and the catheter tip was intended to be situated at the caudal end of the
      urachal cyst. However, the catheter tip accidentally perforated the bladder and
      urine flowed out of the bladder through the catheter. Because the urine diluted
      and washed out the pus in the urachal cyst, the infected urachal cyst was
      successfully drained. Percutaneous drainage and antibiotics allowed resolution of
      the inflammatory process. On the twenty-third day after catheter placement,
      excision of the urachal cyst and partial cystectomy were performed with relative
      ease and without any complications.

PMID- 11523137
TI  - [Ectopic prostatic tissue in retrotrigone of the bladder: a case report].
AB  - We herein report a case of ectopic prostatic tissue in the retrotrigone of the
      bladder. A 35-year-old man was referred to our hospital because of bladder tumor
      which was incidentally discovered on abdominal ultrasonography (US). US and
      computed tomography (CT) showed a tumor in the bladder wall 1.5 cm in diameter.
      Magnetic resonance imaging (MRI) revealed an invasive bladder tumor. Cystoscopy
      showed a non-papillary, wide-based tumor in the retrotrigone of the bladder.
      Transurethral resection of bladder tumor was carried out and pathological
      findings showed ectopic prostatic tissue. This is the 8th case of ectopic
      prostatic tissue in the Japanese literature.

PMID- 11523138
TI  - [Mucinous adenocarcinoma of the prostate: a case report].
AB  - A 64-year-old man presented to our department with urinary retention. Rectal
      examination revealed a small and soft prostate. PSA was within the normal limits.
      Computed tomography showed a low-density area around the prostatic urethra and
      urethrography revealed an irregular prostatic urethra compressed by the prostate.
      We performed transurethral resection of prostate (TUR-P). On resectoscopy, jelly
      like round substances were seen in the bladder. Prostatic urethra and bladder
      neck were covered with a jelly-like substance. Pathological diagnosis was
      mucinous adenocarcinoma of the prostate with bladder neck involvement. One month
      later after TUR-P, we performed radical cystoprostatectomy. Histological findings
      showed the cancer, of which 70-80% was composed of extracellular mucin lakes
      containing floating clumps of tumor cells. Mucin lake was stained with alcian
      blue and PAS. Immunohistochemical study revealed the tumor cells positive for
      carcinoembryonic antigen (CEA) and negative for prostatic specific antigen (PSA).

PMID- 11523139
TI  - [A case of primary adenocarcinoma of the female urethra].
AB  - A 53-year-old female visited our hospital with a complaint of acute urinary
      retention. Transvaginal ultrasonography, computed tomography and magnetic
      resonance imaging showed extreme thickening of the urethral wall.
      Histopathological examination of the transvaginal needle biopsy suggested well
      differentiated adenocarcinoma. She underwent total cysto-urethrectomy with
      partial vaginal wall resection and ileal conduit urinary diversion. Pathological
      diagnosis of the tumor was columnar adenocarcinoma invading into the vaginal wall
      and periurethral connective tissue. Fifty-eight cases of primary adenocarcinoma
      of the female urethra in the Japanease literature are briefly reviewed.

PMID- 11523140
TI  - Preputial calculi: a case report.
AB  - The patient was a 92-year-old male whose chief complaint was urinary retention.
      The X-ray film showed multiple overlapping calcification shadows in the penile
      region. Renal insufficiency was speculated to be due to post-renal obstruction.
      Under the diagnoses of closure of the preputial orifice by balanoposthitis
      followed by urinary retention and preputial calculi, an urgent dorsal incision of
      the prepuce was made. Then, stone removal and indwelling catheter placement were
      performed. Renal function recovered soon after the operation, and the patient
      could urinate freely without catheterization. This case reminds us of the
      significance of surgical treatment for phimosis in elderly patients.

PMID- 11523141
TI  - [Joint diseases of the elderly].

PMID- 11523142
TI  - [Defensins as a mechanism of host defense and innate immunity].
AB  - Antimicrobial peptides, including beta-defensins, are thought to be effective
      agents against opportunistic infections. In humans, three beta-defensins have
      been identified. The first human beta-defensin, hBD-1, is predominantly expressed
      in epithelia of the urogenital tract and has been reported to be constitutive.
      The second and third human beta-defensins, hBD-2 and hBD-3, were isolated from
      psoriatic skin and found to be predominantly expressed in skin and respiratory
      tract. Of note, the hBD-2 gene expression is inducible by various proinflammatory
      agents such as TNF-alpha, IL-1 beta, IL-8, LPS, bacteria, and yeasts. It has been
      shown that LPS-induced expression of hBD-2 in human tracheobronchial epithelial
      cells requires CD14, which may complex with Toll-like receptors (TLRs) to
      ultimately activate NF-kappa B. In addition, beta-defensins have been recently
      reported to promote immune responses by recruiting dendritic and T cells.
      Defensins may play a key role in the mechanism of host defense and innate
      immunity. These defensins, including hBD-2, might provide a new therapeutic
      approach to infectious diseases.

PMID- 11523143
TI  - [Clinical significance of white matter lesion in vascular dementia].

PMID- 11523144
TI  - [Oxidized low density lipoprotein and atherogenesis].

PMID- 11523145
TI  - [Insulin therapy for elder diabetic patients].

PMID- 11523146
TI  - [Molecular mechanism underlying the development of Alzheimer's disease:
      implications of apolipoprotein E and presenilin].

PMID- 11523147
TI  - [Hospitals for the chronic disease--from the viewpoint of services
      administration].

PMID- 11523148
TI  - [The present state and problems of long-team care hospitals].

PMID- 11523149
TI  - [Hospitals for the chronic diseases--from the stand point of a Miyagi Medical
      Association].

PMID- 11523150
TI  - [Hospitals for the chronic diseases--from the stand point of a local
      rehabilitation hospital].

PMID- 11523151
TI  - [Oral care and QOL for the elderly--the recent and future issue for health,
      medical and welfare services].

PMID- 11523152
TI  - [Oral health care by domiciliary visiting for home-bound elderly].

PMID- 11523153
TI  - [Effect of oral health care in prevention of aspiration pneumonia].

PMID- 11523154
TI  - [Oral status and oral care of dependent elderly].

PMID- 11523155
TI  - [Oral care reduces pneumonia of elderly patients in nursing homes, irrespective
      of dentate or edentate status].
AB  - Aspiration of oral secretions and their bacteria, especially gram-negative
      bacilli, is increasingly being recognized as an important factor in pneumonia. We
      investigated whether oral care reduces the frequency of pneumonia in the
      institutionalized elderly. Nurses or caregivers cleaned patients' teeth with
      toothbrushes after each meal, and scrubbed the oropharynx with an applicator with
      povidone iodine (1%) every day. Dentists or dental hygienists gave professional
      care once a week. During follow up, pneumonia decreased significantly in patients
      with oral care. Oral care was of benefit for both edentate as well as dentate
      subjects, although periodontal diseases might cause pneumonia. We suggest that
      oral care may be useful in preventing pneumonia in institutionalized elderly,
      irrespective of dentate or edentate status.

PMID- 11523157
TI  - [Study on risk factors of cerebral amyloid angiopathy].

PMID- 11523156
TI  - [Detection of exhaled CO as a simple non-invasive tool for monitoring acute
      exacerbations of asthma in the elderly].
AB  - Exhaled carbon monoxide (CO) concentrations were measured on a CO monitor by
      vital capacity maneuvers in asthmatic patients either receiving or not receiving
      inhaled corticosteroids, and in nonsmoking healthy control subjects. CO was
      detectable and measured reproducibly in the exhaled air of all subjects. The
      exhaled CO concentrations were higher in asthmatic patients not receiving inhaled
      corticosteroids and similar in asthmatic patients receiving inhaled
      corticosteroids and nonsmoking healthy control subjects (Am J Respir Crit Care
      Med 1997: 156: 1140-1143). All patients with inhaled corticosteroid treatment had
      reductions in exhaled CO concentration and eosinophil cell counts in sputum that
      were accompanied by an amelioration of airway obstruction. These results showed
      that detection of exhaled CO could be a simple non-invasive tool for monitoring
      airway inflammation and acute exacerbation of asthma.

PMID- 11523158
TI  - [Molecular biology of glutamate transporters in Alzheimer's disease].

PMID- 11523159
TI  - [Mechanism for endothelial dysfunction on age].

PMID- 11523160
TI  - [Pathogenesis of idiopathic Parkinson's disease].
AB  - The pathogenesis of idiopathic Parkinson's disease (PD) remains to be elucidated.
      The discovery of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) suggests
      that neurotoxins in the human brain may cause selective depletion of striatal
      dopamine neurons, a hallmark of PD. An endogenous isoquinoline, N
      methyl(R)salsolinol is a most promising neurotoxin candidate, and it was proved
      to be selectively toxic to dopamine neurons in the rat brain by in vivo
      experiments. The level of N-methyl(R)salsolinol in the cerebrospinal fluid
      obtained from PD patients was significantly higher than control. N
      Methyl(R)salsolinol is synthesized by 2 enzymatic reactions from dopamine;
      condensation of dopamine with acetaldehyde into (R)salsolinol by (R)salsolinol
      synthase and N-methylation of (R)salsolinol by neutral(R)salsolinol N
      methyltransferase. The second enzyme, which catabolizes the N-methylation of
      (R)salsolinol, was found to determine the level of the neurotoxin in the brain.
      The activity of neutral(R)salsolinol N-methyltransferase was examined using
      lymphocytes prepared from PD patients, normal controls and diseased controls as
      enzyme source. A significant increase in the activity was confirmed in
      lymphocytes from PD cases compared to normal- and diseased-control. Studies to
      clarify the environmental and genetic factors determining the activity of the
      enzyme are now under the way. The cytotoxicity of N-methyl(R)salsolinol was
      examined using a cultured cell model. N-Methyl(R)salsolinol was found to induce
      apoptotic cell death in a dose-dependent way. The mechanism of apoptosis was
      clarified to be mediated by collapse in mitochondrial membrane potential,
      activation of caspase 3 and fragmentation of nuclear DNA. In addition,
      propargylamines protected the cells from apoptosis. It was suggested that N
      methyl(R)salsolinol and propargylamines have specific binding sites in
      mitochondria which regulate the death signal transduction. Propargylamines might
      be applicable as neuroprotective drugs, which can be orally administrated to PD
      patients.

PMID- 11523161
TI  - [Genetic markers for prevention of osteoporosis].

PMID- 11523162
TI  - [Aged onset of amyloidosis caused by transthyretin gene mutations].
AB  - We have identified that familial amyloid polyneuropathy with middle age onset
      results from missense mutations of the transthyretin gene. In the present study,
      we investigated molecular abnormalities of transthyretin in elderly patients with
      cardiac amyloidosis or amyloid polyneuropathy, using DNA sequencing and protein
      sequencing. We detected 5 cases of transthyretin-related cardiac amyloidosis
      using immunohistochemical techniques. All of them had late-onset, mild or no
      peripheral neuropathy or autonomic dysfunctions, and no family history. Three had
      transthyretin Met30 and two transthyretin Ile50. We also found 15 patients with
      transthyretin-related amyloid polyneuropathy. All of them had late-onset and no
      contributory family history. Twelve had transthyretin Met30, two transthyretin
      Ile50, and one transthyretin Ser109. Clinical manifestations and sequencing
      procedures of six representative patients were also presented. Molecular
      investigation of transthyretin is needed for elderly patients with etiology
      unknown cardiac amyloidosis or amyloid polyneuropathy even if there is no family
      history of amyloidosis.

PMID- 11523163
TI  - [A four-year prospective study on the influence of serum elevated lipoprotein (a)
      concentration on ischemic heart disease and cerebral infarction in elderly
      patients with type 2 diabetes].
AB  - To clarify the influence of elevated serum lipoprotein (a) (Lp(a)) concentration
      on ischemic heart disease (IHD) and the perforating artery occlusion type of
      cerebral infarction (CI) in elderly patients with type 2 diabetes, we measured
      the serum levels of Lp(a) of type 2 diabetic patients (n = 158, 81 men and 77
      women). The group was followed up prospectively for 4 years and the incidence of
      IHD or CI was monitored. The diagnosis of CI was confirmed by computed tomography
      and that of IHD, which includes myocardial infarction and angina pectoris, was
      diagnosed by electrocardiogram and blood chemistry examination, Lp(a)
      concentrations of 20 mg/dl or more were identified as elevated Lp(a) levels and
      Lp(a) concentrations of less than 20 mg/dl were identified as normal Lp(a)
      levels. A Kaplan-Meier survival analysis (log-rank test) assessed the time to
      event rate stratified by an Lp(a) cutoff point of 20 mg/dl. The predictive value
      for CI or IHD events was assessed by multiple logistic regression analysis. The
      probability of IHD events was significantly higher in the elevated Lp(a) group
      than in the normal Lp(a) group without a history of IHD but was similar in the
      two groups for those patients with a history of IHD. There was no significant
      difference between the elevated Lp(a) group and the normal Lp(a) group with
      regard to CI events in patients without a history of CI and with a history of CI.
      On multiple logistic regression analysis, Lp(a), hyperlipidemia and a history of
      IHD were significant predictors of IHD and hypertension, hyperlipidemia and a
      history of CI were significant predictors of CI. These results show that elevated
      serum Lp(a) concentrations is an independent risk factor for IHD, but not for the
      perforating artery occlusion type of CI in type 2 elderly diabetic patients.

PMID- 11523164
TI  - [Comparison between the short program and the long program of post-operative
      rehabilitation of hip fracture for making the critical path].
AB  - Patients receiving operative treatment for fracture are good candidate for
      critical path management. Recently, we have developed a Short Program (SP) for
      post-operative rehabilitation of hip fractures. The purpose of this study was to
      evaluate the effectiveness, the safety and the cost efficiency of this SP, by
      comparing it with the former Long Program (LP) in terms of choosing the better
      program for the critical path. The enrolled patients were over 65 years old, had
      been able to walk by themselves with or without canes, were free from
      neurological diseases like hemiplegia and Parkinson's disease, and without
      pathological fractures. We enrolled 101 patients (mean age: 83.1) for the LP and
      143 patients (mean age: 82.8) for the SP. The operative procedure for these
      patients was internal fixation with a sliding hip screw or prosthetic replacement
      for a femoral head. Length of hospitalization, the rate of recovering walking
      ability, medical expenses during hospitalization, and the types and incidence of
      complications were investigated to determine differences between the SP and the
      LP. Length of hospitalization was significantly shorter in SP patients (p <
      0.01). The ratio of recovering walking ability was equal in both programs, while
      that among the patients with dementia was lower in the SP group. Medical expenses
      were significantly less in SP (p < 0.01). The SP had fever complications than the
      LP group (p < 0.05). As a result, the SP was superior to the LP in terms of
      effectiveness, safety and cost efficiency, thus it was considered to be suitable
      for critical path management of hip fracture cases. However, because recovery of
      walking ability was harder for patients over 85 years old with the SP than with
      the LP, a modified program is necessary for such older patients.

PMID- 11523165
TI  - [Effect of inhaled anticholinergic drug on pulmonary function and quality of life
      in elderly patients with chronic obstructive pulmonary disease].
AB  - Effects of inhaled anticholinergic drug on the physiological function of the
      respiratory system and quality of life (QOL) in elderly patients with chronic
      obstructive pulmonary disease (COPD) have not been fully elucidated. We examined
      the pulmonary function, static respiratory pressures, and ventilation during
      exercise, before and after inhalation of oxitropium bromide (OTB) in 12 male
      patients with COPD (mean age 82.1 +/- 0.6 years). QOL was measured with a St
      George's Respiratory Questionnaire (SGRQ) in the patients. Forced expiratory
      volume in one second was increased by the inhalation of OTB in the patients,
      whereas the ratio of residual volume to total lung capacity was decreased by the
      inhalation. Maximum inspiratory pressure was significantly increased after the
      administration of OTB. Dyspnea sensation during exercise measured on the Borg
      scale was reduced by the inhalation of OTB. The scores of SGRQ were improved by
      one-month treatment with OTB. These results suggest that the treatment with OTB
      are effective for both physiological function and several aspects of QOL in
      elderly patients with COPD.

PMID- 11523166
TI  - [Effects of acupuncture therapy on low back pain and/or knee pain in elderly
      patients].
AB  - In April 1999, 75 elderly patients (mean age: 79 years old) with low back pain
      and/or knee pain visited an acupuncture and physical therapy unit in a geriatric
      hospital. A cross-sectional study was carried out in order to evaluate the
      effects of acupuncture therapy on low back pain and/or knee pain in elderly
      patients. Among them, 60 patients answered that their pain diminished following
      their therapy. The proportion of patients who were treated with acupuncture
      therapy were higher in these 60 patients than the other 15 patients (55.5% vs.
      26.7%, p = 0.05). The result suggests that acupuncture therapy may be able to
      relieve low back pain and/or knee pain in elderly patients. However, 46% of the
      patients with acupuncture therapy were also treated with other types of physical
      therapy. Further studies should be recommended to confirm the effects of
      acupuncture therapy on low back pain and/or knee pain.

PMID- 11523167
TI  - [Present status and problems in medical care for demented patients using public
      counselling facilities].
AB  - To clarify the present status and problems in medical care for the elderly with
      dementia, 103 cases were studied according to the descriptive records obtained at
      a public counselling facility for dementia, based on interviews with patients'
      families. Their records were analysed based on their background, severity of
      dementia (clinical dementia rating: CDR), and counselling content. There were 75
      demented patients with a CDR score of 1 or more, and 50 of them were women aged
      54 to 90, while the remaining 25 men were aged 55 to 88. The consultation content
      was clustered into 5 codes: code 1, evaluation of dementia and/or dementia
      related symptoms including psychiatric symptoms and behavioral disturbance; code
      2, methods to manage patients; code 3, methods to take a patient to a medical
      institution; code 4, questions regarding medical treatment and drugs prescribed
      at present; code 5, information on the welfare resources provided. In most of the
      75 patients, the degree of dementia deteriorated insidiously without any physical
      symptoms. The key person and/or caregiver was usually an elderly spouse, and the
      family noticed dementia only after cognitive impairment progressed with or
      without troublesome symptoms. Hallucination was a common troublesome symptom.
      Concerning consultation content, codes 1, 2, and 3 were common, while 13 cases
      had dissatisfaction with their medical treatment. Therefore, it was necessary to
      explain the significance of early diagnosis of dementia to families and their
      caregivers. There were also many families who felt strain and wondered about what
      hospital or department to take the patient to. In addition, it seemed that
      explanation on the clinical course and adverse drug reactions, advice for the
      correspondence with psychiatric symptoms and abnormal behaviour, and information
      services concerning utilization of social resources was not yet sufficient.

PMID- 11523168
TI  - [Falling accidents among metropolitan elderly resulting in emergency ambulance
      transfer].
AB  - The aim of this study was to examine the frequency and number of falling
      accidents in the the elderly population and to investigate the characteristics of
      the accidents. The investigation was performed in 58 Tokyo metropolitan townships
      for a one-year period from September 1st, 1997, and the 517 cases, in which
      persons were over 65 years old, fell down were studied (136 men, 381 women). The
      yearly accident frequency for 1,000 elderly over 65 population was 4.13 cases for
      men and 7.88 cases for women, being 1.9 times higher in women. Also the number of
      accidents in each township was significantly correlated to the population of the
      elderly over 65 (men r = 0.674, women r = 0.846, p < 0.001). The analysis by age
      showed the percentage of accidents in single-family housing among the oldest-old
      population was significantly higher than the young-old population (p < 0.05) for
      both men and women. According to logistic regression analysis results, injured
      body part and the form of dwelling house were significantly correlated as risk
      factors of fracture (p < 0.05). The odds ratio of injured body part was 7.559
      (95% CI 4.926-11.598), and that of the form of dwelling house was 1.660 (95% CI
      1.067-2.584), showing that injury of limbs and the accidents in single-family
      housing would increase risk of fracture. Promoting preventative measures for
      falling accidents in single-family housing appears important in the prevention of
      falling accidents among the metropolitan elderly.

PMID- 11523169
TI  - [A case of gliomatosis cerebri in an elderly woman].
AB  - Gliomatosis cerebri is a rare form of glioma, which diffusely extends to both
      cerebral hemispheres. Because it sometimes fails to show severe neurological
      symptoms in spite of diffuse invasion, the antemortem diagnosis is difficult. We
      report a case of a 77-year-old woman, who was admitted with progressive left
      hemiparesis and dysarthralgia. Plain CT scan of the brain showed almost no
      abnormal findings. MRI T2-weighted image revealed widespread and nearly
      symmetrical extension of a high intensity area from the corpus callosum to the
      deep white matter of both cerebral hemispheres. Open biopsy of the brain showed
      glioblastoma multiforme, which finally confirmed the clinical diagnosis of
      gliomatosis cerebri. We also review the classic and recent literatures.

PMID- 11523170
TI  - [An elderly case of idiopathic dilatation of the right atrium in which right
      sided heart failure was exacerbated by drug-induced bradyarrhythmia].
AB  - We describe an elderly case of idiopathic dilatation of the right atrium in which
      right-sided heart failure was exacerbated by drug-induced bradyarrhythmia. An 84
      year-old man, who had a 10-year history of episodic edema, was treated with
      proscillaridin and verapamil hydrochloride at another hospital. He had
      experienced a poor appetite and general malaise 2 months previously, and
      exertional dyspnea 10 days previously. On admission, he had jugular venous
      dilatation, systemic edema, and hepatomegaly. On auscultation, a third heart
      sound originating from the right ventricle and systolic murmur of tricuspid
      regurgitation were heard. An admission electrocardiogram showed an atrial
      standstill and junctional escape rhythm with a QRS rate of 31 beats/minute. Chest
      roentgenogram revealed a bilateral pleural effusion and cardiomegaly with a
      cardiothoracic ratio of 76%, but no pulmonary congestion. Echocardiogram
      disclosed idiopathic dilatation of the right atrium and secondary tricuspid
      regurgitation. He was given a diagnosis of right-sided heart failure due to
      idiopathic dilatation of the right atrium exacerbated by bradyarrhythmia, which
      was suspected to derive from the side effects of proscillaridin and verapamil
      hydrochloride. Thus, these agents were withheld. In addition, the patient reduced
      sodium intake and was treated with diuretics and beta-adrenergic agonist.
      Thereafter, right-sided heart failure markedly improved. At the time of the last
      follow-up 16 months after discharge, he felt well.

PMID- 11523171
TI  - [CHF arising after low dose THP-COP chemotherapy in an elderly patient with
      malignant lymphoma].
AB  - A 76-year-old woman was admitted with a one-month history of low grade fever and
      dizziness. She had a palpable right supraclavicular lymph node. Abdominal
      ultrasonography showed swollen lymph nodes around the abdominal aorta. A specimen
      from the right supraclavicular lymph node showed malignant lymphoma (diffuse
      large B cell type). We started chemotherapy according to the low-dose THP-COP
      protocol (pirarubicin, cyclophosphamide, vincristine and prednisolone) on the
      31st hospital day. Since no adverse effects were detected after two low-dose
      cycles, the patient received a third course with standard doses on the 87th
      hospital day. The total dose of pirarubicin was 72 mg/m2. Two days after the
      third course started, she suffered from dyspnea caused by congestive heart
      failure. A chest X-ray showed advanced cardiomegaly, severe congestion and
      bilateral pleural effusion. These conditions improved with transvenous
      administration of diuretics, a vasodilator and phosphodiesterase inhibitor. In
      this case, congestive heart failure developed even though the total dose of
      pirarubicin was lower than in previous reports of this complication. When the THP
      COP protocol is indicated in elderly patients, cardiotoxicity should be monitored
      even if the total dose of pirarubicin is very low.

PMID- 11523172
TI  - [Swallowing rehabilitation in two elderly patients with cerebral infarction].
AB  - We report two cases of cerebral infarction in which swallowing function improved
      following swallowing rehabilitation. Patient 1 was an 82-year-old man, who was
      admitted due to rheumatoid arthritis and multiple cerebral infarction, suffering
      from aspiration pneumonia. The abnormality of swallowing was assessed by the
      water swallowing test and videofluorography. It has been reported that
      videofluorography is useful in the diagnosis of aspiration. Three weeks after the
      start of swallowing rehabilitation, the serum level of inflammatory markers and
      the chest X-ray had returned to normal. His score on the water swallowing test
      had improved. Patient 2 was a 68-year-old [correction of 62] man, who was
      admitted with severe hemiplegia, dysphagia and dysarthria. One month after the
      swallowing rehabilitation, videofluorography showed that the magnitude of
      aspiration into the trachea had decreased and the pooling of barium in the
      piriform sinus had disappeared. The patient could begin taking a little food by
      mouth. These results suggest that swallowing rehabilitation will be affect the
      clinical improvement of swallowing function and help preventing aspiration
      pneumonia in our hospital.

PMID- 11523173
TI  - [An elderly case of lung cancer presenting with symptoms of orbital metastasis].
AB  - An 88-year-old woman was first referred to an eye clinic in mid-May 2000 because
      of limitation of ocular movement. A right orbital tumor was recognized on orbital
      CT scans and she was referred to our hospital. A chest X-ray film showed an
      abnormal mass in the right middle lung field, so she was admitted for further
      investigations. Adenocarcinoma was diagnosed by transbronchial lung biopsy. The
      right orbital tumor was thought to be a metastasis from the lung cancer. She
      received radiation therapy for the metastatic orbital tumor. However, two months
      after the onset of symptoms, she died due to progressive systemic metastasis. In
      summary, we report an elderly lung cancer patient whose initial symptoms were
      related to orbital metastasis.

PMID- 11523174
TI  - Tech shock and the virtues of incrementalism.

PMID- 11523176
TI  - An update on certifying home health care.

PMID- 11523175
TI  - Compliance: a lose-lose situation?

PMID- 11523177
TI  - 'Work smarter, not harder' to save your practice money.

PMID- 11523178
TI  - Electronic paper & pencil: 6 easy steps to a low-cost electronic medical record.

PMID- 11523179
TI  - Coping with the stress of being sued.

PMID- 11523180
TI  - Putting clinical guidelines into practice.

PMID- 11523181
TI  - Spirituality and your practice.

PMID- 11523182
TI  - Outbreak of Salmonella paratyphi B var java due to contaminated alfalfa sprouts
      in Alberta, British Columbia and Saskatchewan.

PMID- 11523183
TI  - When to consider a COX-2 inhibitor for osteoarthritis of the knee.

PMID- 11523184
TI  - Understanding inflammatory disorders of the upper extremity.

PMID- 11523185
TI  - To prevent malpractice litigation, document the breast mass workup.

PMID- 11523186
TI  - What genetic testing can tell you about breast cancer risk.

PMID- 11523187
TI  - Hard choices when breast cancer threatens.

PMID- 11523188
TI  - Guidelines for ethical conduct for the PA profession.

PMID- 11523189
TI  - Dual diagnosis. Effective recognition and management of severe mental illness and
      substance abuse.

PMID- 11523190
TI  - Chronic hepatitis C: implications for the primary care clinician.
AB  - The seeds of an epidemic were sown 2 decades ago, and PAs need to be alert for
      those at risk for developing chronic hepatitis C before cirrhosis, liver failure,
      or liver cancer develops. Identifying the patient at risk is as uncomplicated as
      asking the right questions in the right setting.

PMID- 11523191
TI  - The sound of the whistle-blower above the noise.

PMID- 11523192
TI  - Reducing the dangers of pediatric pneumococcal disease with a new vaccine.

PMID- 11523193
TI  - Circumscribing the "essential obligations" of a profession.

PMID- 11523194
TI  - Hypercholesterolemia in elderly patients. Evidence-based medicine applied to a
      common clinical question.

PMID- 11523195
TI  - How physician assistants use and perceive complementary and alternative medicine.
AB  - The use of complementary and alternative medicine (CAM) is growing in the United
      States. Patients and their health care providers are increasingly accepting of
      complementary and alternative therapies. The purpose of this study was to
      identify physician assistants' (PAs') attitudes, beliefs, knowledge, training,
      recommendations for, and personal use of CAM. A random sample of 500 practicing
      PAs was sent a four-page, 78-item survey investigating their personal use of,
      recommendations for, and perceptions of the efficacy and safety of complementary
      and alternative therapies. Of PAs eligible to complete the survey, 50% responded.
      Chi-square analyses found a significant relationship between knowledge level and
      recommendation for CAM; status of use and belief that CAM exerts a placebo
      effect; status of use and recommendation for CAM; and source of information on
      CAM and recommendation for CAM. With the increasing prevalence of use of CAM, PAs
      need to be informed regarding CAM therapies.

PMID- 11523196
TI  - Minimizing the threat of nosocomial infection.

PMID- 11523197
TI  - Introduced into evidence. PAs are recommending, and using, CAM.

PMID- 11523198
TI  - Testing......3,2,1.

PMID- 11523199
TI  - Families with deaf members: American Annals of the Deaf, 1996 to 2000.
AB  - The authors provide an overview of 21 articles from several countries focusing on
      families with deaf members published in the literary issues of the American
      Annals of the Deaf from 1996 to 2000. Four categories were identified:
      Interaction and Involvement, Support Services, Stress and Coping, and Decision
      Making. The articles represent a commendable expansion of focus from the mother
      child dyad to increased attention to fathers, siblings, extended family members,
      and significant nonfamily members such as deaf adults. The heterogeneity of
      families was a striking factor, even within those studies dealing with relatively
      homogeneous populations. Services appeared to be most effective within middle
      class, educated family units, illustrating the need for more comprehensive
      services sensitive to the needs of families from less affluent backgrounds and
      with lower levels of education. In general, services to families with deaf
      children may be characterized as better than in the past but still in need of
      significant sensitivity and improvement. The presence of a deaf child in a family
      with hearing parents may cause stress, but parents have the flexibility to
      respond in a positive and beneficial way, especially when provided adequate
      information and support. The idea that hearing parents go through a grieving
      process involving the identification of deafness in their child seems to be an
      overstatement.

PMID- 11523200
TI  - Solving word problems: more than reading issues for deaf students.
AB  - Deaf and hearing college students were given 30 mathematics problems to solve.
      The initial 15 were presented as numeric/graphic problems, followed by 15
      corresponding word problems, with both conditions sequenced for a progressive
      increase in problem complexity. Each word problem described the kind of shape and
      measurement information that was presented in its corresponding numeric/graphic
      problem. The results showed that the deaf college students, regardless of reading
      level, were comparable in performance to the hearing college students when
      solving the numeric/graphic problems and the initial, least complex set of
      corresponding word problems. However, as the complexity of the descriptive
      information in the word problems increased along with the complexity of the
      problem situations, the performance scores of the deaf students decreased. No
      comparable decrease was observed in the hearing students' scores. While reading
      ability level was associated with the deaf students' lower scores when solving
      word problems, the analyses show that other factors also contributed.

PMID- 11523201
TI  - Parents as adult learners in family-centered early education.
AB  - Several concepts from the adult learning literature are described that relate to
      working with parents of young children who are deaf. It is proposed that an adult
      learner perspective makes an important contribution to the family-centered
      philosophy and knowledge base that guide the development of practice in early
      intervention. Three areas are discussed: the context for adult learning, that is,
      the life situation of adults, including their social roles and responsibilities
      and experience; learning related to transitions in the adult life cycle; and
      transformative learning, which examines the ways people make changes in how they
      understand their experience. Implications for practice in early childhood
      education are presented.

PMID- 11523202
TI  - A deaf child learns to read.
AB  - The purpose of the present study was to document the literacy development of a
      deaf child in a preschool setting. The child, Jeffrey (a pseudonym), was observed
      in his preschool deaf class for 9 months. Data came primarily from extensive
      field notes from observations of Jeffrey throughout the school day, with
      particular emphasis on his actions during literacy-related events. A secondary
      source of data was the transcript of an interview with Jeffrey's parents.
      Findings indicated that Jeffrey went through several levels as he learned to
      read: (a) focusing on pictures and illustrations in books, (b) reading familiar
      words in context, (c) focusing on sign print, (d) relating sign print to written
      English, and (e) reading written English independently.

PMID- 11523203
TI  - Egocentric language in deaf children.
AB  - Egocentric language is a generalization of Piaget's egocentric speech concept
      (1926/1969) investigated by Vygotsky (1962). Behaviors of eight children ages 2
      to 5 years with profound congenital deafness were analyzed using six classes of
      egocentric language: motor reaction activity, silent lips articulation, murmur,
      oral-facial mimics, body expression, and vocalization. No child had received oral
      or sign language training. All attended videotaped play sessions. Events in which
      children engaged in "dialogue" with themselves or a toy, while pursuing a
      specific solution, were observed. Such extralinguistic behavior moves the
      thinking process toward problem solving like that of hearing children.
      Consequently, teachers should not interrupt when a deaf child is playing with or
      signing or vocalizing to a toy, because this behavior may be the manifestation of
      a reflexive moment and the generator of a decision process fundamental for
      cognitive development. Vocalization by a deaf child does not indicate willingness
      to speak; it merely manifests symbolic reasoning. Silent lips articulation and
      oral-facial mimics have the same effect and can also be interpreted.

PMID- 11523204
TI  - HIV/AIDS knowledge and information sources among deaf and hearing college
      students.
AB  - A sample of 34 deaf undergraduate college students at Gallaudet University and 46
      hearing undergraduate college students at the University of Maryland Baltimore
      County completed a questionnaire that asked about their knowledge and sources of
      information concerning the human immunodeficiency virus and acquired
      immunodeficiency syndrome (HIV/AIDS). The deaf students had significantly lower
      scores on an "HIV/AIDS Knowledge Index" than the hearing students. This
      difference could not be explained by the deaf students' gender, class standing,
      family structure, or father's or mother's education level. The deaf students
      obtained more of their information about HIV/AIDS from family and friends than
      the hearing students, who relied to a greater extent on teachers, television, and
      reading material. The interpersonal sources used by the deaf students are more
      prone to factual errors than formal sources. Deaf students need methods of
      educating themselves about HIV/AIDS that are more accurate and that recognize the
      importance of sources as well as the content of information.

PMID- 11523205
TI  - Parental training and involvement in sexuality education for students who are
      deaf.
AB  - The study examined whether schools for the deaf were providing services to assist
      parents in communicating with their children about sexuality (including sexual
      signs) and whether parents were involved in the sexuality education curriculum
      within their child's school. The Sexuality Curriculum Questionnaire for Educators
      of Students Who Are Deaf (Getch & Gabriel, 1998) was completed by 71 educators
      teaching sexuality curricula in schools for the deaf across the United States.
      Results indicated that parents were more likely to be involved in approval and
      development of their children's sexuality education than to receive assistance
      with sexuality education from the schools. Although the level of parental
      participation in curriculum development and approval is encouraging, the number
      of parents actually participating in curriculum development and approval remains
      low.

PMID- 11523206
TI  - Unique issues faced by deaf individuals entering substance abuse treatment and
      following discharge.
AB  - Several barriers can frustrate a deaf individual's intention to enter a substance
      abuse treatment program. Because few specialized programs work with the Deaf, it
      is difficult to determine the factors that influence a deaf individual's desire
      to maintain sobriety following completion of a residential treatment program. A
      sample of 100 individuals was drawn from the Minnesota Chemical Dependency
      Program for Deaf and Hard of Hearing Individuals, a model hospital-based
      inpatient treatment program. The study participants were asked to complete
      pretreatment and posttreatment surveys upon admission and discharge,
      respectively, in addition to a follow-up survey, to help determine which
      background factors might be associated with different treatment outcomes for deaf
      and hard of hearing persons who completed treatment in the program. Results are
      presented for the pretreatment and posttreatment assessments, and for the follow
      up survey. Study limitations are discussed and recommendations are given for
      future treatment programs serving deaf and hard of hearing individuals.

PMID- 11523207
TI  - An analysis on the diagnostic values of transcranial Doppler and angiography in
      transient ischemic attack.
AB  - The accuracy and diagnostic values of transcranial Doppler (TCD) in transient
      ischemic attack (TIA) caused by the stenosis or occlusion of intracranial or
      extracranial blood vessels were investigated. Of the 50 TIA patients receiving
      routine TCD examinations, 39 cases (77%) were diagnosed as having unilateral or
      bilateral stenosis or occlusion of MCA, ACA, siphon segment of internal carotid
      artery, which was furthermore confirmed by digital subtraction angiography (DSA)
      or MRA, 11 (22%) cases were normal. An analysis on the TCD findings of the flow
      patterns and hemodynamic changes of the stenotic or occluded blood vessels was
      made in comparison with that obtained by angiography. It was showed that
      angiography demonstrated 17 unilateral MCA stenosis, 47 bilateral multi-stenosis,
      1 occlusion of the siphon segment of the internal carotid artery, while TCD
      revealed 17 unilateral stenosis, 64 bilateral stenosis, 1 occlusion respectively,
      with an accordance rate of 78.7%. It was concluded that the hemodynamic changes
      secondary to the stenosis of the basalcranial arteries, especially the moderate
      to severe stenosis or occlusion, might be an important risk factor for TIA. TCD
      examination achieved significant clinic values in the diagnosing of TIA.

PMID- 11523208
TI  - Effect of diazepam on the contents of amino acids and free radical during
      ischemia/reperfusion injury.
AB  - The protective effect and mechanism of diazepam on ischemia neurons during
      cerebral ischemia and reperfusion were studied. Sixty-three Wistar rats were
      divided randomly into nine groups: control group (n = 7), ischemia (is) groups
      including subgroups of is3 h, is3-h/rep1-h, is3-h/rep2-h, is3-h/rep3-h(n = 7 in
      each group), diazepam treated groups (10 mg/kg, i.p.), including subgroups of is3
      h, is3-h/rep1-h, is3-h/rep2-h, is3-h/rep3-h (n = 7 in each group) with Zea
      longa's animal model of middle cerebral artery occlusion. The comparison between
      the ischemia group and diazepam-treated group showed that diazepam could
      obviously decrease the production of glutamate, asparate, MDA and increase the
      synthesis and release of GABA, SOD and GSH-PX. It was concluded that diazepam
      exerted its protective effects on neurons through complex mechanisms of
      regulating the synthesis and release of excitotary/inhibitory amino acids and
      free radicals.

PMID- 11523209
TI  - Effect of jianpiyiqi prescription on the expression of heat shock proteins in
      acetic acid-induced chronic gastric ulcer rats.
AB  - To investigate the effect of Jianpiyiqi prescription on the expression of heat
      shock proteins (HSPs) and the changes of HSPs in gastric-ulcerated rats, the rat
      model of chronic gastric ulcer was induced by acetic acid. The SABC
      immunohistochemical method was used to observe HSP70 of mucosa around the gastric
      ulcer. Imaging analysis was performed. Western dot blot was used to detect HSPs
      contents in the plasma and gastric mucosal homogenate in each group. The results
      showed that HSP70 contents of the mucosa around the gastric ulcer in the model
      group and ranitidine-treated group were increased as compared with control group
      (P < 0.01). Jianpiyiqi could increase the expression of HSP70 of the mucosa
      around the gastric ulcer further as compared with that in the model group and
      ranitidine-treated group (P < 0.01). The HSP70 contents in the serum and mucosa
      in the model group and ranitidine-treated group were increased as compared with
      control group (P < 0.01, P < 0.05 respectively). HSP70 of serum and mucosa in the
      Jianpiyiqi-treated group was higher than in the model group and ranitidine
      treated group (P < 0.05, P < 0.01 respectively). It was concluded that HSP might
      play a role in the process of pathophysiology of gastric ulcer. Jianpiyiqi could
      enhance gastric ulcer-healing through the protective mechanism of HSPs.

PMID- 11523210
TI  - Immunophenotyping of lymphocyte T and B in the peripheral blood of systemic lupus
      erythematosus.
AB  - The immunophenotyping expression levels of lymphocyte in the peripheral blood
      from 21 patients with active systemic lupus erythematosus (SLE) were analyzed by
      using the immunofluorescence labeling-flow cytometry technique to investigate the
      immunophenotyping expression of lymphocytes T and B in the peripheral blood of
      active SLE patients and its clinical value. It was showed that, compared with
      normal controls, the expression of CD3+, CD4+ and the ratio of CD4+/CD8+ in the
      peripheral blood of these patients were decreased (P < 0.01), while the
      expression of CD8+, CD20+ was significantly increased (P < 0.01). It was
      suggested that both T and B cells in patients with active SLE involved in
      immunoregulation, were activated. The abnormal expression of lymphocyte
      immunophenotyping could influence the immune reaction in SLE patients, which
      might be one of the important pathogenesis factors in SLE.

PMID- 11523211
TI  - The clinic study on synchronous detection of HCV RNA in the plasma and PBMC of
      hepatitis C patients.
AB  - In order to increase the positive detection rate of HCV RNA in the patients with
      chronic hepatitis C (CHC), RT-PCR was used to synchronously detect HCV RNA in the
      plasma and peripheral blood mononuclear cells (PBMC) of 583 CHC patients with a
      continuously elevated level of ALT for more than one year. The results showed
      that the positive detection rate of HCV RNA in the plasma of the CHC patients was
      19.2%, while 24.5% in PBMC. It was demonstrated that the positive detection rate
      for HCV RNA in PBMC was obviously higher than that detected in plasma. To
      synchronously detect HCV RNA in PBMC by using RT-PCR can increase the positive
      detection rate of HCV RNA in the CHC patients.

PMID- 11523212
TI  - Study on Fas/Fas-L expression in liver tissue and hepatocyte apoptosis in
      patients with hepatitis gravis.
AB  - To explore the expression of Fas/Fas-L in liver tissue of hepatitis gravis
      patients and its implication in hepatocyte apoptosis, Fas/Fas-L expression and
      cell apoptosis was detected by the means of inmmunohistochemistry and terminal
      deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL). It was
      found that in the 20 patients with clinical hepatitis gravis, Fas in hepatocytes
      showed strong expression and Fas-L also showed intensive expression in
      infiltrating lymphocytes and scattering hepatocytes. The apoptosis existed in all
      the samples, scattering in the areas of inflammatory, necrotic area and hepatic
      lobule. It was suggested that the overexpression of Fas/Fas-L could cause the
      death of hepatocytes and thus the occurrence of hepatitis gravis. The apoptosis
      caused by Fas might be one of the important pathogeneses of hepatitis gravis.
      Among the detected samples, apoptosis and necrosis coexisted, indicating that
      both two types of cellular death were closely associated with the pathogenesis of
      hepatitis gravis.

PMID- 11523213
TI  - [Experimental research about effectiveness of transarterial chemoembolization
      (TACE) in an animal model of hepatocellular carcinoma].

PMID- 11523214
TI  - The changes of protein kinase C activity in peripheral blood lymphocytes in the
      patients with obstructive jaundice and the implication.
AB  - The roles of protein kinase C (PKC) signal pathway in the pathogenesis of
      obstructive jaundice were studied. PKC from cytosolic and membrane fractions of
      peripheral blood lymphocytes (PBL) in 51 patients with obstructive jaundice and
      16 cases of normal controls was isolated and purified. The activities of PKC were
      determined by radioactive isotope gamma-32P-ATP-catalyzing assay. The results
      showed that the total PKC activities in PBL in the patients with obstructive
      jaundice were significantly increased as compared with those in the normal
      controls (P < 0.01). Moreover, the membrane PKC activities and their percentages
      of the total PKC activities were higher in obstructive jaundice group than in
      those in the normal controls (P < 0.05). The total PKC activities in PBL in the
      patients with obstructive jaundice were significantly positively correlated with
      the levels of soluble IL-2 receptor (sIL-2R) (r = 0.58, P < 0.01) and the degree
      of jaundice (T-BIL) (r = 0.67, P < 0.01) in serum. It was concluded that the
      activities of PKC signal pathway was related with the degree of T-BIL. PKC signal
      pathway might took part in the activation of T-lymphocytes in the patients with
      obstructive jaundice and play an important role in the immune regulation and the
      assessment of pathosis in the patients with obstructive jaundice.

PMID- 11523215
TI  - Gene therapy of HSV-TK transferred by the EBV based expression vector on
      experimental hepatocellular carcinoma.
AB  - To study the therapeutic effects of herpes simplex virus thymidine kinase (HSV
      TK) gene transferred by the EBV-based expression vector (pDR2) on experimental
      hepatocellular carcinoma, pDR2-TK gene was delivered into human hepatocellular
      carcinoma cell line SMMC-7721 by using liposome-mediated transfection technique,
      and then gene expression was detected by RT-PCR, and the killing effects were
      examined through MTT method. In the nude mice hepatoma model, the antitumor
      effects of pDR2-TK/GCV system was evaluated in terms of tumor growth. MTT results
      showed that the pDR2-TK/GCV had cytotoxic effect and about 70% SMMC-7721 cells
      were killed when GCV was at 1000 mumol/L. In vivo experiment showed that the
      tumor size in nude mice with transferred pDR2-TK gene was significantly smaller
      than that in control group (P < 0.01). On the 10th day the tumor in 3 mice (60%)
      disappeared completely after GCV treatment. It is concluded that the pDR2-TK/GCV
      system has marked killing effects on the experimental hepatocellular carcinoma.

PMID- 11523216
TI  - Apoptosis and Fas system are significantly involved in the process of liver
      cirrhosis converting into hepatocellular carcinoma.
AB  - To investigate the roles of apoptosis and the Fas system (Fas, Fas ligand,
      soluble Fas) in the process of liver cirrhosis (LC) converting into
      hepatocellular carcinoma (HCC), expression of Fas and Fas ligand (FasL) in 49 LC
      and 36 HCC samples was detected by immunohistochemical method. Apoptosis was
      detected by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling
      (TUNEL) method. Serum soluble Fas (sFas) levels in 28 cases of LC and 27 cases of
      HCC were measured by enzyme-linked immunosorbent assay (ELISA) method. Compared
      with LC, apoptotic indices (AI) in HCC tissues were significantly reduced (P <
      0.001), expression of Fas was decreased (P < 0.05), and that of FasL was
      increased (P < 0.05). Serum sFas levels in HCC patients were significantly higher
      than those in normal controls. Down-regulation of Fas expression, up-regulation
      of FasL expression in hepatocytes and elevation of sFas level in serum might
      contribute to tumor escape from immune surveillance of the body. Apoptosis and
      the Fas system are significantly involved in the process of liver cirrhosis
      converting into hepatocellular carcinoma.

PMID- 11523217
TI  - Osteogenic potential of cultured bone marrow stromal cells transfected with
      transforming growth factor beta 1 gene in vitro.
AB  - To study the osteogenic potential of cultured bone marrow stromal cells (BMSCs)
      transfected with transforming growth factor beta 1 (TGF-beta 1) gene in vitro,
      cultured BMSCs were transfected with the complexes of pcDNA3-TGF-beta 1 and
      Lipofectamine Reagent in vitro. The cell proliferation was detected by MTT method
      and the morphological features of transfected BMSCs was observed. ALP stains and
      PNP method were used to measure ALP activity. In addition, the collagen type I
      propeptides and mineralized matrixes were examined by immunohistochemical
      staining and tetracycline fluorescence labeling respectively. The morphological
      and biological characters of the transfected BMSCs were similar to those of
      osteoblasts and the cell proliferation was promoted. The cell layer displayed
      strong positive reaction for ALP stains and immunohistochemical staining. ALP
      activity and collagen type I expression increased remarkably after transfection.
      Mineralized matrixes formed earlier and more in transfected BMSCs as compared
      with control group. It is concluded that transfecting with TGF-beta 1 gene could
      promote the osteogenic potential of cultured BMSCs.

PMID- 11523218
TI  - Human vascular endothelial growth factor cDNA cloning and expression in
      osteoblasts.
AB  - Human vascular endothelial growth factor (VEGF) cDNA was amplified by nested
      polymerase chain reaction method from the HL60 cells. Then a pCD-hVEGF165
      recombinant plasmid was constructed. Rabbit osteoblasts were transfected with pCD
      hVEGF165 plasmid by lipofectin mediated gene transfer. The transient expressive
      results were detected by immunohistochemical method. It was observed that the
      expression of human VEGF gene was detected 72 h after transfecting distinctly.

PMID- 11523219
TI  - The influence of phorbol ester on the effect of tamoxifen in breast cancer cells.
AB  - To investigate the correlation between the activity of kinases in the growth
      factor signal transduction pathway and the development of resistance of breast
      cancer to tamoxifen, reporter gene regulated by the regulating fragment of CCD1
      was transfected into the MCF-7 cells, and the influence of tamoxifen on the
      reporter gene expression was examined under different conditions of TPA
      treatment. Our results showed that the reporter gene expression was inhibited by
      tamoxifen and promoted by TPA. Furthermore, tamoxifen exerts an agonist effect on
      the reporter gene expression when the cells was treated by TPA previously for 12
      h. It is concluded that TPA could induce estrogen-like effect of tamoxifen on
      estrogen receptor positive breast cancer cells and it may be one of the
      mechanisms responsible for the development of tamoxifen resistance.

PMID- 11523220
TI  - Expression of androgen receptor in meningiomas.
AB  - In order to investigate the expression of androgen receptor (AR) in meningiomas
      and its relation to tumor proliferative potential, we examined the expression of
      AR and proliferating cell nuclear antigen (PCNA) by avidine-biotin complex
      immunohistochemistry in 39 cases of meningiomas. Of the 39 cases of meningiomas,
      20(51%) showed positive AR immunoreactivity. The AR expression positivity rates
      were 31% (6/19) in benign meningiomas, 58% (7/12) in atypical meningiomas, 87.5%
      (7/8) in malignant meningiomas, respectively. In addition to the tumor cells,
      cells of microvascular endothelial proliferation were frequently AR positive.
      Malignant meningiomas had a significantly higher percentage of AR positive cells
      compared with atypical and benign meningiomas (P < 0.05). The mean proliferating
      cell nuclear antigen labeling index (PCNA LI) was significantly higher in the
      malignant meningiomas when compared with atypical meningiomas (P < 0.05) and
      benign meningiomas (P < 0.05). AR positive meningiomas had higher PCNA LI than AR
      negative meningiomas (P < 0.05). The expression of AR in tumor tissues was
      significantly related with PCNA LI. These data indicated that AR in the
      meningiomas was correlated with histological grade and AR might participate in
      the growth of these tumors and tumor angiogenesis. The measurement of AR in these
      tumors may indirectly represent tumor growth potential.

PMID- 11523221
TI  - The effect of hydroxyapatite ultrofine powder on the immunity function of tumor
      bearing mice.
AB  - The inhibitory effect of hydroxyapatite ultrofine powder (HAUFP) on tumor and the
      effect on the immunity function of body were investigated. The levels of IL-2 in
      the spleen cells and serum TNF levels in the tumor-bearing mice at the 7th day
      and 14th after peritoneal injection of HAUFP were detected by using the methods
      of colorimetric analysis of MTT and crystal purple decoration, respectively. The
      disappearance of the ascites of the mice was observed. The results showed that
      the levels of IL-2 and TNF in the tumor-bearing mice were higher obviously in the
      drug-treated group than in the control group (P < 0.01), the ascites growth was
      inhibited. It was suggested that HAUFP could increase the levels of IL-2 and TNF
      of the tumor-bearing mice and improve the immune function of body.

PMID- 11523222
TI  - Novel gelatin-adriamycin sustained drug release system for intravesical therapy
      of bladder cancer.
AB  - To reduce recurrence in the patients with bladder cancer after tumor removal
      through open surgery or transurethral resection, a form of gelatin-adriamycin
      sustained drug release system was developed and its release kinetics both in
      vitro and in vivo, its efficacy in inhibiting BIU-87 bladder tumor cell growth in
      vitro and its safety in vivo were studied. The results showed that this system
      controlled adriamycin release over a period of 21 days in vitro and significantly
      inhibited BIU-87 cell growth. When this system was injected into rabbit bladder,
      it sustained adriamycin release for 12 days and the released drug could diffuse 1
      cm around the injection point. No major complications were observed except minor
      acute nonspecific cystitis that could be tolerated well by the animals. This
      study suggests the possibility of applying this system locally in treating
      bladder cancer.

PMID- 11523223
TI  - Total cavopulmonary connection for complex cardiac anomalies with the functional
      single ventricle.
AB  - From Aug. 1999 to Feb. 2001, 8 patients with complex congenital heart diseases,
      including 5 cases accompanied by hypoplastic left ventricle and 3 by hypoplastic
      right ventricle, were subjected to total cavopulmonary connection (TCPC). Eight
      cases underwent the operation under cardiopulmonary bypass and 7 of whom under no
      cardiac clamp. Seven cases received cavopulmonary anastomosis by flaring method
      and one case by end-side anastomosis. All the patients underwent the intracardiac
      tunnels to drain inferior vena cava and plus 4 mm fenestration except one. The
      results showed that 6 patients had postoperative oxygen saturation more than 90%,
      sinus rhythm, no anastomostic stoma obstruction, no flow regurgitation and CVP <
      16 cmH2O. Two (25%) patients died postoperatively from high venous pressure of 18
      20 cmH2O, finally from cardiac failure and anoxima. It was concluded that TCPC
      was an effective treatment for complex congenital cardiac diseases, especially
      with ventricular maldevelopment. Intracardiac tunnel plus 4 mm fenestration and
      flaring cavopulmonary anastomosis could prevent the postoperative complications.
      Larger anastomotic stoma, venous pressure less than 16 cmH2O and artery
      saturation more than 90% might indicate excellent TCPC procedures in our
      experience.

PMID- 11523224
TI  - Monitoring of biological responses of tumor cells after irradiation with 99mTc
      MIBI--an in vitro study.
AB  - To explore the possibility to employ 99mTc-MIBI to monitor biological response of
      tumor cells after irradiation and to observe the relation between the radiation
      doses and the uptake levels of 99mTc-MIBI in tumor cells, the cells were
      irradiated with a single dose of 2 Gy, 10 Gy and 20 Gy respectively. The uptake
      of 99mTc-MIBI in each dosage group was determined before and 24, 48, 72 h after
      irradiation respectively. Apoptosis index (AI), plating efficiency (PE) of tumor
      cells was simultaneously determined. There was a positive correlation between
      uptake levels of 99mTc-MIBI and AI(r = -0.91, P < 0.05). A negative correlation
      was noted between the uptake levels and PE (r = -0.86, P < 0.05). It is suggested
      that 99mTc-MIBI may be used as a tracer to monitor the change of viability state
      of tumor cells after being irradiated with different doses.

PMID- 11523225
TI  - Dynamic renal scintigraphy in diagnosis of upper urinary tract obstruction in
      transplanted kidney.
AB  - Nuclide renal dynamic imaging was performed on 88 (110 times) transplanted
      kidney. Two kinds of renal scintigraphic characteristics were identified in
      recipients with supravesical obstruction of the graft. First, the regular type
      was characterized by radioactivity defect area in kidney parenchyma during early
      uptake period followed by ureteropelvic retention. Second, the tubular type was
      typified by cortical retention and attenuation in collecting system during the
      whole test period with a special sign of "hollow kidney". Non-obstructive dilated
      calyces showed similar signs as the regular type. Acute rejection reaction and
      tubule necrosis demonstrated obstructive time-activity curves. However, the
      radioactivity retention appeared in cortex. It was suggested that dilated calyces
      and obstructive renogram might not be reliable evidence for upper urinary tract
      obstruction. The signs of radioactivity attenuation in kidney parenchyma during
      early uptake period followed by ureteropelvic retention may be more valuable for
      the evaluation. As for tubular obstruction, specified "hollow kidney" was the
      characteristic sign which is helpful for the diagnosis.

PMID- 11523226
TI  - A comparative study of the effects of magnetic stimulation and electric
      stimulation on peripheral nerve injury in rat.
AB  - The influence of pulsed magnetic stimulation (MS) on the sciatic nerve injury was
      investigated. Thirty rats were divided into three groups equally: MS group (A),
      electric stimulation (ES) group (B) and the control group (C). The MS and ES were
      applied immediately after the first 10 min of the sciatic nerve crush. Sciatic
      function index (SFI), toe spreading reflex (TSR), muscular weight and volume were
      measured after the experiment. The TSR of in the groups A and B occurred at 4th
      day while in the control group it occurs at 10th day. There was statistically
      significant difference in SFI between groups A and B (P < 0.01). The weight and
      volume of the gastrocnemius muscle were statistically greater in the groups A and
      B than in the control group (P < 0.01). The effect of MS was similar to that of
      ES. It was suggested that the application of MS immediately after the nerve
      injury might have an important clinical value as it can accelerate functional
      recovery and prevent or minimize muscle atrophy. The technique is easily to
      operate, non-invasion, painless and permits tolerance of high intensity output to
      be used.

PMID- 11523227
TI  - Y specific sequence gene analysis of single fetal nucleated erythroblasts from
      the peripheral blood of pregnant women.
AB  - The single cell isolation technique was used to detect fetal nucleated
      erythroblasts (FNRBCs) at a single cell level from the peripheral blood of
      pregnant women in order to investigate the feasibility of this method for
      noninvasive prenatal diagnosis. Single fetal nucleated erythroblasts were
      isolated from the peripheral blood samples from 51 pregnant women (14 to 26 weeks
      of gestation) by micromanipulation techniques after density gradient
      centrifugation. Nested polymerase chain reaction method was used to amplify the
      SRY gene. It was found that the concordance rate of amplification results with
      real fetal sex was 82.61%. The sensitivity and specificity were 80% and 87.50%
      respectively. It was suggested that it is feasible and promising in non invasive
      prenatal diagnosis to detect fetal nucleated erythroblasts at a single cell level
      by using micromanipulation techniques.

PMID- 11523228
TI  - Levels of lipid peroxides and superoxide dismutase in peritoneal fluid of
      patients with endometriosis.
AB  - In order to evaluate the changes of lipid perioxides (LPO) and superoxide
      dismutase (SOD) levels in peritoneal fluid in patients with endometriosis, the
      levels of LPO and SOD in peritoneal fluids from infertile women with
      endometriosis and with normal pelvis were measured. The result showed that the
      levels of LPO but SOD was elevated significantly in peritoneal fluid from women
      with endometriosis than in women with normal pelvis (P < 0.01). It is suggested
      that free oxygen radicals may be involved in the pathogenesis of endometriosis
      associated infertility.

PMID- 11523229
TI  - Study on the role of interleukin-4 in experimental murine systemic candidiasis.
AB  - In order to investigate the role of interleukin-4 (IL-4) in experimental murine
      systemic Candidiasis, we created the intact and dexamethasone-induced
      immunosuppressed murine systemic Candidiasis models. In these models, two-site
      ELISA and RT-PCR were applied to determine the level of IL-4 protein and mRNA
      expression in spleens respectively, clone forming units (CFUs) of infected
      kidneys were determined with the plating dilution method, and mean survival time
      (MST) of the mice was recorded. The results showed that, when compared with the
      controls, protein level of IL-4 increased in both intact mice infected with
      lethal doses of yeast (day 3, P < 0.05; day 7, P < 0.001) and immunosuppressed
      mice infected with sublethal doses of yeast (day 3, P > 0.05; day 7, P < 0.05).
      Furthermore, the level of IL-4 was higher on day 7 than on day 3 after infection
      (P < 0.001 and P < 0.05 respectively in two groups). The tendency of IL-4 mRNA
      expression was similar with that of IL-4 protein. As for fungal loads in kidneys,
      CFUs were significantly higher on day 7 than on day 3 after infection (P < 0.001
      in both groups). Mice in both groups succumbed to infection within several days.
      It was suggested that IL-4 might play a promoting role in the development of
      murine systemic Candidiasis.

PMID- 11523230
TI  - The expression of Fas/FasL in peripheral blood lymphocytes and the level of IL-2
      in serum of patients with condyloma acuminata.
AB  - In order to investigate the role of the expression of the Fas/FasL in peripheral
      blood lymphocytes (PBLC) and the level of IL-2 in serum of patients with
      condyloma acuminata (CA) in the immune pathogenesis of CA, flow cytometry,
      indirect immunofluorescence labeling and ELISA were performed to detect the
      expression of the apoptotic regulatory proteins Fas/FasL in PBLC and the level of
      IL-2 in serum of 60 patients with different course of CA. The results showed that
      the expression of Fas/FasL in PBLC of the group of short course in CA was
      significantly higher than that of the normal controls (P < 0.05); the expression
      of Fas, FasL in PBLC of the group of long course CA was significantly higher than
      that of the group of short course and the normal controls (P < 0.05 and P < 0.01,
      respectively); the level of IL-2 in serum of the group of short and long course
      CA was significantly lower than that of the group of normal controls (P < 0.01);
      the negative relation was revealed between the expression of Fas/FasL in PBLC and
      the level of IL-2 in serum of patients with CA (r = -0.76, P < 0.01). It was
      suggested that the abnormal apoptosis in PBLC and decreased level of IL-2 in
      serum of CA might play an important role in the course of CA.

PMID- 11523231
TI  - The anti-proliferative effect of inhibitor of telomerase on cultured retinal
      pigment epithelial cells.
AB  - In order to provide a new method for treating proliferative vitreoretinopathy
      (PVR), the effects of anti-proliferation and apoptosis induction of inhibitors of
      telomerase and heat shock protein 90 (Hsp90) on the cultured retinal pigment
      epithelial (RPE) cells were investigated. The rate of apoptosis cells was
      measured by using TUNEL on the cultured RPE cells, the co-cultured RPE cells with
      inhibitor of telomerase (camptothecin) or the co-cultured RPE cells with
      inhibitor of Hsp90 (geldanamycin). The cell proliferation status was measured in
      the above three groups by using MTT method. The rate of apoptosis in the RPE
      cells co-cultured with camptothecin or geldanamycin was increased remarkably (P <
      0.05). MTT showed the rate of growth inhibition was 8.4%, 32.3% and 72.3% at the
      concentrations of camptothecin 1 mumol/L, 5 mumol/L, 10 mumol/L, respectively,
      and 6.5%, 30.9%, 71.9% at the concentrations of geldanamycin 1 mumol/L, 5
      mumol/L, 10 mumol/L, respectively. It was concluded that telomerase and Hsp90 can
      promote the proliferation of the cultured RPE cells, while the inhibitor of them
      can induce apoptosis and inhibit the growth of the RPE cells.

PMID- 11523232
TI  - [Transmural ERP-dispersion from epi-, mid-and endomyocardium in healthy and
      hypertrophied dog myocardium].

PMID- 11523233
TI  - Comparison of arrhythmias among different left ventricular geometric patterns in
      essential hypertension.
AB  - The differences of arrhythmias among distinct left ventricular geometric patterns
      in the patients with essential hypertension were studied. 179 patients with
      essential hypertension received 24 h dynamic ECG recording, ambulatory blood
      pressure monitoring, echocardiography examination, etc. According to the
      examinations, left ventricular geometric patterns and arrhythmias were
      identified. The comparison of morbidity of arrhythmias between the left
      ventricular remodeling group and the normal geometric pattern group was
      performed. The multiple stepwise regression analysis was carried out to identify
      the independent determinants of arrhythmias. After these predictors were
      controlled or adjusted, the severity of arrhythmias among different left
      ventricular geometric patterns was compared. It was found that the morbidity of
      atrial arrhythmia, ventricular arrhythmia and complex ventricular arrhythmias in
      the left ventricular remodeling group was significantly higher than in the normal
      geometric pattern group respectively. There were many independent factors
      influencing on arrhythmias in essential hypertension. Of all these factors, some
      indices of left ventricular anatomic structure, grade of hypertension, left
      atrial inner dimension, E/A, diastolic blood pressure load value at night and day
      average heart rate and so on were very important. After the above-mentioned
      factors were adjusted, the differences of the orders of arrhythmias between
      partial geometric patterns were reserved, which resulted from the differences of
      the geometric patterns. Many factors contributed to arrhythmias of essential
      hypertension, such as grade of hypertension, LVMI, LA, PWT and so on. The
      severity of arrhythmias was different in different left ventricular geometric
      patterns.

PMID- 11523234
TI  - Effect of the vacuolation of Helicobacter pylori.
AB  - Cytotoxic test in vitro combined with cytochemical stain, fluorescent stain,
      transmission electronmicrograph was used to study the vacuolated effect by
      helicobacter pylori (H. pylori) (Toxin+) and its pathological mechanism. 78.26%
      patients with peptic ulcer associated with H. pylori was infected with H. pylori
      (Toxin+), while 42.86% patients with gastritis was infected with H. pylori
      (Toxin+). It was positive in vacuole with acridine orange and acid phosphatase
      stain. Transmission electronmicrograph of vacuole revealed the presence of
      abounding membrane. There was a closed relationship between infection with H.
      pylori (Toxin+) and peptic ulcer disease. The vacuole induced by H. pylori
      (Toxin+) was autophagosome, which was pathological phenomenon induced by toxin.

PMID- 11523235
TI  - Construction and expression of eukaryotic expressing vector pCH510 of polypeptide
      CH50 and its chemotaxis and antitumor function by in vivo transfection.
AB  - To construct an eukaryotic expressing vector that expresses CH50, a recombinant
      Cell I-Hep II bifunctional-domain polypeptide of human fibronectin, and to
      investigate the chemotaxis to immune cells and the inhibitory effect on the
      growth of tumor by the expression of the plasmid in vivo, the plasmid was
      constructed by DNA recombination. Gene transfection was performed in vitro and in
      vivo. The expressed product was identified by Western blot. The chemotaxis after
      gene transfection in vivo was observed by histotomy and staining of muscle
      tissues. The inhibition of gene transfection on solid tumor was observed in mice.
      The results showed that plasmid pCH510 was constructed by the recombination of
      the 5'-terminal noncoding region and signal peptide coding region of human
      fibronectin cDNA and cDNA fragment coding CH50 polypeptide with a 3'-terminal
      noncoding region of human FN cDNA, and the insertion of the recombinated fragment
      into plasmid pcDNA3. 1. After transfection with plasmid pCH510, NIH3T3 cells
      could produce CH50 polypeptide. The transfection of plasmid pCH510 by the
      injection in muscle of mouse could produce the effects of chemotaxis on immune
      cells and the inhibition on the growth of solid tumor. It is concluded that
      plasmid pCH510 can express in cells and in vivo in mouse. The expression of the
      plasmid in vivo has a chemotactic effect on immune cells and can inhibit the
      growth of solid tumor.

PMID- 11523236
TI  - Studies on metal phthalocyanine as a dual functional mimic enzyme.
AB  - Four phthalocyanines (iron tetracarboxylphthalocyanine, copper
      tetracarboxylphthalocyanine, manganese tetracarboxylphthalocyanine, cobalt
      tetracarboxylphthalocyanine) were used as dual functional mimic enzymes of
      superoxide dismutase (SOD) and catalase (CAT). The first function, eliminating O2
      , was proved by using riboflavine-methionine photoreduction method in the
      concentration range of 10(-5) to 10(-6) mol/L. The second function, clearing out
      H2O2, was demonstrated by means of spectrophotometry with the decomposing
      percentage being increased with the increase of the concentration of the
      imitating compounds. Measurements of metal phthalocyanines, SOD and CAT by the
      liver homogenate technique of mice showed that they had obvious action of
      decreasing the lipid peroxidation.

PMID- 11523237
TI  - The effect of polymorphisms of MTHER gene and vitamin B on hyperhomocysteinemia.
AB  - The relationship between hyperhomocysteinemia and coronary artery disease (CAD)
      was investigated and the influence of environmental factors (Folate, VitB12) and
      genetic factors [N5, N10-methylenetetrahydrofolate reductase gene (MTHFR) or
      MTHFR gene mutation] on plasma homocysteine (Hcy) levels and the risk of CAD
      observed. Fifty-one CAD patients and 30 CAD-free subjects were recruited in the
      study. The polymorphisms of MTHFR gene were analyzed by PCR-RFLP and plasma total
      Hcy levels were measured by high performance liquid chromatography with
      fluorescence detection. Plasma folate and vitamin B12 concentrations were
      measured by an automated chemiluminescence method. It was found that mean total
      plasma Hcy concentrations were significantly higher in CAD patients than in CAD
      free subjects (P < 0.01). The differences were also apparent among the three
      genotypes of MTHFR gene in CAD group (P < 0.05). There was no significant
      difference in the genotype distributions and allele frequencies between the two
      groups. A strong inverse correlation was found between folate or vitamin B12 and
      plasma Hcy levels according to MTHFR genotype (P < 0.01). It was concluded that
      hyperhomocysteinemia is a new independent risk factor for CAD. However, MTHFR
      gene mutation alone does not relate significantly to the morbidity of CAD since
      hyperhomocysteinemia and its influence on the risk of CAD are decided by both
      environmental and genetic factors. Supplementary treatment with vitamins B can
      effectively lower the plasma levels of Hcy, thus maybe reducing the risk of CAD.

PMID- 11523238
TI  - Model TJ-IV computer-assisted vectorcardiogram analysis system.
AB  - During last 16 years we have successfully developed the computer-assisted
      vectorcardiogram analysis systems: model TJ-I, TJ-II, and TJ-III, but some
      technical problems remained unresolved, such as the recognition accuracy for
      vectorcardiograms, measurement of the parameters of complicated QRS waves, the
      ratio of T loop length to width, and the area of spatial vectors etc. A new
      system, model TJ-IV was designed to resolve these technical problems. The system
      was equipped with a 586 computer with a CPU of 120 MHz. Special new low-noise
      amplifier was employed and C language was used for programming. Three graph
      recognition techniques were used to enhance the accuracy of VCG recognition. 32
      orthogonal electrocardiograms and vectorcardiograms were displayed and printed,
      and 566 parameters of vectorcardiograms were calculated. Our results with 150
      cases showed that the system had high accuracy of graph recognition, and
      parameter calculation and the results were essentially consistent with those of
      manipulative methods. We were led to concluded when compared with TJ-III system,
      the new version has higher accuracy of processing and measurement for
      vectorcardiograms, is able to process more vectorcardiographic parameters, with
      higher processing speed.

PMID- 11523239
TI  - Clinical study on the treatment of 325 cases of atrioventricular node reentrant
      tachycardia by radiofrequency catheter ablation.
AB  - In order to improve the efficacy of modified inferior method or middle method of
      radiofrequency catheter ablation (RFCA) in the treatment of atrioventricular node
      reentrant tachycardia (AVNRT), the clinical data of 325 cases of AVNRT from March
      1992 to Feb. 2000 being subjected to the treatment of RFCA were retrospectively
      analyzed. The results showed that the successful rate was increased and
      recurrence was decreased year by year. In the recent 4 years the effective rate
      was up to 100%. The complication of three grade of AVB occurred in 3% and
      recurrent rate in 9.1% before March 1996, but both of them were zero in the last
      3 years. The time of RFCA procedure and X-ray exposure was significantly reduced.
      It was concluded that ablating more than 3 targets by modified inferior method or
      middle method with energy titrating and strict endpoint was the crux of obtaining
      satisfactory therapeutic effects and preventing recurrence.

PMID- 11523240
TI  - [Electrocardiography of accessory atrioventricular pathway action of anterior
      septal and mid-septal].

PMID- 11523241
TI  - Short-coupled variant of torsade de pointes.
AB  - Presented in this paper were 3 cases of a special kind of polymorphic ventricular
      tachycardia (VT). The clinical manifestation was recurrent syncope without
      organic heart disease. The electrocardiogram (ECG) was characterized by normal QT
      intervals with short-coupled variant of torsade de pointes. The efficacy of
      treatment with class I, II, III antiarrhythmic drugs was not apparent but
      verapamil had an excellent therapeutic effect for it. This kind of VT had a high
      incidence of sudden death, so it was very important for physicians to identify
      and treat it promptly with long-term verapamil. The mechanism of short-coupled
      variant of torsade de pointes was unclear. It probably had some relationship with
      triggered activity or imbalance of autonomic nervous system.

PMID- 11523242
TI  - Effect of antisense oligodeoxynucleotide directed to NF-kappa B-RelA on Bcl-XL
      mRNA in extended drug resistance leukemia cell line HL-60/E6.
AB  - To explore the effect of NF-kappa B on bcl-x gene transcription in extended drug
      resistance leukemia cell line HL-60/E6, drug-resistant subline HL-60/E6 was
      derived by intermittently exposing HL-60 cells to 6 ng/ml epirubicin. Indirect
      immunofluorescence was used to demonstrate the location of NF-kappa B-RelA in HL
      60/E6 cells. FCM analysis and RT-PCR were used to detect the efficiency of
      liposome-mediated ODN transfection and the change of bcl-XL mRNA levels after 5
      mumol/L phosphorothioate (PS)-derivatized antisense (AS) oligodeoxynucleotide
      (ODN) directed to RelA was transferred into HL-60/E6 cells. The results showed
      that RelA remained persistently active and located at the nuclei of HL-60/E6
      cells, but in the cytoplasm of HL-60 cells, the efficiency of liposome-mediated
      ODN transfection was significantly higher than that of null ODN (P < 0.01 in 4 h,
      6 h, 12 h, 24 h). Exposure of HL-60/E6 cells to 5 mumol/L AS-PS-ODN directed to
      RelA led to a maximal 40% decline of bcl-XL mRNA levels within 8 h. The
      inhibition rate of bcl-XL mRNA was (15 +/- 1.79)%, (28 +/- 2.34)%, (40 +/-
      3.47)%, (20 +/- 1.54)%, in 4 h, 6 h, 8 h, 15 h, respectively, but it was less
      than 15% in control group. It was concluded that NF-kappa B was involved in
      regulating bcl-x transcription. It was suggested that NF-kappa B was an important
      factor for drug resistance in leukemia cells.

PMID- 11523243
TI  - Accuracy and consistency of respiratory inductive plethysmography for overnight
      tidal volume measurement.
AB  - To validate the accuracy and consistency of respiratory inductive plethysmography
      (RIP) in measuring tidal volume after an overnight sleep, tidal volumes of 18
      patients with suspected sleep-disordered breathing and 8 normal volunteers were
      measured simultaneously with RIP (VTRIP) and with an ultrasonic airflow meter
      (VTUFM) before and after an unstrained overnight sleep on supine and lateral
      decubitus. The bias of the VTRIP was expressed as (VTRIP-VTUFM)/ VTUFM.100%,
      limits of agreement between VTRIP and VTUFM was measured by averaged bias +/- 2
      s. Results showed that in normal subjects, the bias of RIP before and after
      overnight sleep was precise and consistent in both supine (0.7% and -1.6%) and
      lateral decubitus (3.7% and -0.56%). In these patients, the bias of RIP before
      and after sleep in supine also remained small (1.9% and 1.7%), but it became
      larger in lateral decubitus (24.5% and 20.4%) and 11.5% exceeded the limits of
      agreement observed in the evening. The patients' body mass indices (BMI) were
      higher than those of normal subjects (median 34.2 vs. 27.8 kg/m2). Pooled data
      showed that the bias of VTRIP in the morning on lateral decubitus but not on
      supine was correlated to BMI (Spearman R = 0.32, n = 52, P = 0.02). Thus, we were
      led to conclude that the accuracy of VTRIP overnight was precise and consistent
      in normal subjects, but the deviation of VTRIP measured on lateral decubitus in
      patients especially in those with excessive obesity was greater, thus, the method
      should not be used for quantitative determination.

PMID- 11523244
TI  - Three-dimensional ultrasonography in obstetrics: the clinical value.
AB  - To investigate the clinical value of three-dimensional ultrasonography (3DUS) in
      obstetrics, various 3DUS rendering methods including surface mode, transparent
      mode and multiplanar mode were employed to scan 30 fetuses in second and third
      trimester by using the transabdominal volume transducer. The results showed that
      surface mode could vividly demonstrate the surface morphologic features of the
      fetuses, as well as the stereo-shape and the spatial relationship among the
      surface structures. The face, limbs, umbilical cord and outer genitalia of the
      fetus could be well displayed by surface mode. Transparent mode could reveal the
      bony structures under the surface, such as ribs, vertebrae, crania, etc. The
      result was not affected by the sophisticated curvature of these bony structures
      and the success rate was up to 100%. When rendered by multiplanar mode, the
      region of interest (ROI) could be viewed from different directions. It should be
      concluded that 3DUS could serve as a supplement to two-dimensional
      ultrasonography (2DUS). 3DUS might play an important role in prenatal diagnosis
      and enhance the diagnostic confidence level of the physicians.

PMID- 11523245
TI  - The study of ovarian artery hemodynamics in patients with infertility by color
      Doppler energy.
AB  - Seventy-four cases of infertility were examined to study the hemodynamics of the
      bilateral ovarian arteries at 21st day during the corpus luteum phase by color
      Doppler energy(CDE) and color Doppler flow imaging (CDFI). All the patients were
      verified by laparoscopy, fallopian tube patency examination and ovarian function
      test. Twenty-two healthy women served as controls. The results showed that the
      difference of resistance index(RI) and pulsatility index (PI) of bilateral
      ovarian arteries between the infertility and the normal controls had statistical
      significance (P < 0.01), and the PI showed negative correlation with the
      thickness of endometrium (left side: r = 0.724, P < 0.01; right side: r = 0.756,
      P < 0.01). The results also showed that CDE was more sensitive than CDFI in
      displaying the ovarian arteries. It could be concluded that the elevated
      resistance of ovarian artery during the corpus luteum phase was one of the
      important factors that resulted in infertility.

PMID- 11523246
TI  - Effects of extracellular ATP on survival of sensory neurons in the dorsal root
      ganglia of rats.
AB  - ATP was added to the cultured sensory neurons obtained from the dorsal root
      ganglia of the neonatal rats and PBS was added to serve as control. MTT assays
      were conducted to evaluate the survival and activity of the cultured neurons. And
      the silicone regenerative chamber was used after the sciatic nerve incision of
      the mature SD rat. 1 mmol/L ATP was injected into the left chamber and 0.09%
      natrium chloride was injected into the right chamber as controls. The changes of
      nitric oxide synthase (NOS) activity in the corresponding dorsal root ganglia
      were measured histochemically and image analysis was also performed 4 days after
      the sciatic nerve injury. The results showed that extracellular ATP could enhance
      the survival of the neurons and the number of NOS positive neurons were
      significantly different between the ATP and control groups (P < 0.05). It was
      suggested that extracellular ATP had neurotrophic effect on neurons survival and
      could inhibit the NOS activity of the sensory neurons after the peripheral nerve
      incision, hence exerting the protective effect on the neurons, which was valuable
      for nerve regeneration after nerve injury.

PMID- 11523247
TI  - [Biomechanical study of the pedicular resorbable substitute in osteoporotic
      spine].

PMID- 11523248
TI  - Direct gene transfer into rabbit peripheral nerve in vivo.
AB  - Exogenous gene suture was used to achieve peripheral nerve anastomoses to probe
      into the feasibility that the sites of anastomoses of nerves directly transfer
      gene and thus enable gene to be expressed at the sites of anastomoses under the
      condition that perfect nerve anastomoses are ensured. PCMV beta plasmid
      containing cytomegalovirus promoter (CMV promoter) and Escherichia coli (E. coli)
      beta-Galactosidase (beta-Gal) structural gene (lacZ gene) was conducted. A soaked
      medical 8-0nylon suture was used to perform epineurial repair of rabbit sciatic
      nerve. In the control group a suture soaked in sucrose PBS was used, while in the
      experimental group a suture soaked in PCMV beta plasmid solution was applied. The
      sites of anastomoses of nerves by stages were taken out, and beta-Gal
      histochemical staining was performed and beta-Gal enzyme activity was assayed
      with 5-bromo-4-chloro-3-indolyl-beta-D-galactoside. Results showed that the sites
      of anastomoses of nerves were taken out 2 days, 7 days, 14 days and 30 days
      respectively after the operation. The beta-Gal histochemical stains at the sites
      of anastomoses showed no indigo positive cells at different stages in the control
      group, whereas displayed indigo positive cells in the experimental group. In the
      control group, no beta-Gal enzyme activity was detected at different stages after
      operation, but in the experimental group, beta-Gal enzyme activity could be
      detected from the 3rd day to the 30th day after operation. It was concluded that
      by using exogenous gene suture, exogenous gene could be transferred to the sites
      of peripheral nerve and expressed the exogenous gene expression products with
      bioactivity, which provided the feasibility of using gene therapy to accelerate
      the recovery of nerve function.

PMID- 11523249
TI  - Expression of multidrug-associated protein, P-glycoprotein, P53 and Bcl-2
      proteins in bladder cancer and clinical implication.
AB  - The expression of multidrug resistant proteins in bladder cancer and clinical
      implication was studied. Expression of multidrug-associated protein (MRP), P
      glycoprotein (P-gp), P53 and Bcl-2 proteins were detected by using
      immunohistochemical method in 40 specimens of bladder transitional cell
      carcinoma. The results showed that the positive rate of MRP, P-gp, P53 and Bcl-2
      was 52.5%, 57.5%, 47.5% and 62.5% respectively. The positive rate of MRP, P-gp,
      P53 and Bcl-2 in the grade I, II and III of tumors was 46.3%, 38.5%, 38.5%,
      23.1%; 52.9%, 39.8%, 47.1%, 76.4%; 60.0%, 80.0%, 60.0%, 90.0% respectively. The
      positive rate of MRP, P-gp, P53 and Bcl-2 in 24 primary tumor specimens was
      37.5%, 41.7%, 33.3%, 45.8% and that in 16 cases in recurrent specimens receiving
      chemotherapy 75.0%, 81.3%, 68.8%, 87.5% respectively. It was suggested the
      positive rate of MRP, P-gp, P53 and Bcl-2 was increased with the advance of tumor
      grade. The positive rate of four proteins in all recurrent cases was
      significantly increased (P < 0.05). The expression of MRP, P-gp, P53 and Bcl-2
      proteins might be the important factors for chemotherapy failure.

PMID- 11523250
TI  - Reactivity of human preformed natural antibodies with various porcine pancreatic
      cells.
AB  - The reactivity of human preformed natural antibodies (PNAbs) with various porcine
      pancreatic cells and its isotypes was investigated. Eighteen serum samples from
      patients with insulin-dependent diabetes mellitus (IDDM) and 20 serum samples
      from healthy human subjects were collected. The frozen sections of the pig
      pancreas were incubated with these sera, and subsequently incubated with FITC
      conjugated goat antihuman IgG and IgM monoclonal antibodies. The reactivity of
      human PNAbs with various porcine pancreatic cells was determined by indirect
      immunofluorescence staining technique. The results showed that 55.6% of IDDM
      patients and 55.0% of healthy human individuals contained PNAbs against porcine
      endocrine cells. However, the percentage of strongly reacting sera in the patient
      group was significantly increased as compared with that in the control group. All
      used sera from IDDM patients and 95% of sera from healthy controls could react to
      one or more of the various pancreatic cell types, including: endocrine cells,
      exocrine cells, vascular endothelial cells, ductal epithelial cells and
      macrophages. The isotypes of PNAbs contained both IgG and IgM. In view of
      strongly positive reactivity of PNAbs with various porcine pancreatic cells,
      pretransplantly cross-matching test and graft pretreatment may be necessary for
      survival of islet transplants.

PMID- 11523251
TI  - Ligustrazini inhibits endotoxin induced PAI-1 expression in human umbilical vein
      endothelial cells.
AB  - Plasminogen activator inhibitor 1 (PAI-1) is one of important coagulant factors.
      Endotoxin lipopolysaccharide (LPS) induces thrombosis by stimulating PAI-1
      secretion of vascular cells (EC). Using sandwich enzyme-linked immunosorbent
      assay (ELISA) and Northern blot, was investigated the effects of Chinese medicine
      ligustrazini on PAI-1 expression in EC and LPS-stimulated EC. The results showed
      that ligustrazini inhibited both basal and LPS-induced PAI-1 mRNA expression in
      EC. The effect of ligustrazini on LPS-induced PAI-1 secretion worked in a dose
      dependent manner. This study provided theoretic and experimental evidence for use
      of ligustrazini against septic shock and cardiovascular diseases.

PMID- 11523252
TI  - Effect of 17 beta-estradiol on the brain damage and metabolic changes in rats.
AB  - An in vivo model of glutamate excitotoxicity in which glutamate is applied to the
      cortex of rats through a microdialysis probe has been used to investigate the
      neuroprotective processes initiated by 17 beta-estradiol. Rats were pre-treated
      with 17 beta-estradiol i.v. before local application of glutamate. The
      experimental results showed that pre-treatment with 17 beta-estradiol
      significantly reduced the size of the glutamate-induced lesion. In the
      microdialysates, the peak of lactate observed immediately after glutamate
      application was significantly higher and longer lasting after 17 beta-estradiol
      pre-treatment. The level of extracellular glucose was markedly decreased
      concomitantly to the increase in lactate, but no difference could be observed
      with and without 17 beta-estradiol pre-treatment. These suggest a new
      neuroprotective mechanism of 17 beta-estradiol by activating glutamate-induced
      lactate production. This effect on lactate production and lesion reduction is
      estrogen receptor dependent and is abolished totally by estrogen antagonist
      tamoxifen. It was also demonstrated here that high lactate subserves estrogen
      neuroprotection during glutamate toxicity.

PMID- 11523253
TI  - The protective effect of propofol on erythrocytes during cardiopulmonary bypass.
AB  - To evaluate the relationship between erythrocyte injury and intracellular calcium
      ion overload, and the protective effect of propofol on erythrocytes during
      cardiopulmonary bypass (CPB), 40 children with congenital heart diseases who
      underwent surgical repair under CPB were studied. The patients were randomly
      divided into two groups: control group (group C) and propofol group (group P).
      Anesthesia was maintained in the patients in group P with 6 mg.kg-1.h-1 propofol,
      and those in the group C inhaled 1%-2% isoflurane. The blood samples were taken
      before CPB, at the 30th min of CPB, at the end of CPB, and 2 h and 24 h after CPB
      to measure the content of erythrocyte intracellular calcium ion (E-Ca2+), Ca(2+)
      Mg(2+)-ATPase and Na(+)-K(+)-ATPase activities, index filtration of erythrocytes
      (IF), mean corpuscular volume (MCV) and the concentration of plasma free
      hemoglobin (F-HB). Results showed that in the control group, E-Ca2+, IF, MCV and
      F-Hb were gradually increased and Ca(2+)-Mg(2+)-ATPase and Na(+)-K(+)-ATPase
      activities were decreased. The increase of E-Ca2+ was linearly paralleled to IF,
      MCV and F-Hb. In propofol group, all the above-mentioned parameters were
      significantly improved (P < 0.05). This study suggests that erythrocyte injury is
      related to elevation of intracellular calcium during CPB and propofol has a
      protective effect on erythrocyte injury.

PMID- 11523254
TI  - Cytokine-induced cell surface expression of adhesion molecules in vascular
      endothelial cells in vitro.
AB  - Regulation of the adhesion molecules expression by cytokine in vascular
      endothelial cells was investigated. Human umbilical vein endothelial cells
      (HUVEC) were stimulated with cytokines, TNF-alpha (1-250 U/ml) or IL-1 beta (0.1
      50 U/ml) for 24 h. HUVEC were also cultured with cytokines, TNF-alpha (100 U/ml)
      or IL-1 beta (10 U/ml), for 4-72 h, cell surface expression of adhesion molecules
      (ICAM-1 and VCAM-1) were detected and quantitated by immunocytochemical methods
      and computerized imaging analysis technique. Adhesion molecules expression were
      up-regulated by TNF-alpha, IL-1 beta in a concentration- and time-dependent
      manner. Some significant differences were observed between the effects of
      cytokines on the ICAM-1 and on VCAM-1 expression. Cytokines might directly induce
      the expression of ICAM-1 and VCAM-1 in vascular endothelial cells. Our
      observations indicate differential functions of the two adhesion molecules during
      the evolution of inflammatory responses in stroke.

PMID- 11523255
TI  - A randomized, controlled, single-blind trial of leflunomide in the treatment of
      rheumatoid arthritis.
AB  - The efficacy and safety of leflunomide (LEF) in the treatment of rheumatoid
      arthritis (RA) were evaluated and the comparison with methotrexate's (MTX's) was
      performed in a 12-week, single-blind, randomized, parallel trial for treating 81
      patients with RA. There were 56 cases in LEF group and 25 cases in MTX group. The
      dose of LEF was 20 mg per day and MTX 15 mg per week. All patients took oxaproxin
      simultaneously at the 4th to 6th week after the trail. The results showed that
      the general effective rate and notable effective rate were 94.64% and 73.21% in
      LEF group, 72% and 44% in MTX group, respectively, with the differences being
      statistically significant between the two groups (P < 0.05). LEF and oxaprozin
      could obviously improve the symptoms, signs and joint functions. The incidence of
      side reactions was lower in LEF group (17.86%) than in MTX group (40.00%, P <
      0.05). LEF had a good therapeutic effect for RA, especially for refractory RA and
      had slight side reactions, and could be regarded as a superior immunosuppressive
      agent used in the treatment of RA and other connective tissue diseases.

PMID- 11523256
TI  - Study on modification of the Misgav Ladach method for cesarean section.
AB  - 172 cases of pregnant women scheduled for delivery by cesarean section were
      randomly assigned to 59 cases in modification group with modified Misgav Ladach
      technique, 57 cases in Misgav Ladach group with Misgav Ladach technique and 56
      cases in Pfannenstiel group with Pfannenstiel technique from May to Dec. 1999.
      The modified points included: transversely incising the fascia 2 to 3 cm, then
      dividing it bluntly; without opening and dissociating the visceral peritoneum;
      two layers suturing of low transverse uterine incision; closing the skin by
      continuous suturing. Results showed the average delivery time in the modification
      group was (3.6 +/- 2.6) min and (5.7 +/- 2.9) min in the Misgav Ladach group (P <
      0.05). Median operating time was (28.3 +/- 5.4) min in modification group
      compared with (27.5 +/- 6.5) min in the Misgav Ladach group (P > 0.05). Average
      blood loss was (128 +/- 35) ml in modification group compared with (212 +/- 147)
      ml in the Pfannenstiel group (P < 0.05). It was concluded that the modified
      Misgav Ladach technique not only preserved all advantages of Misgav Ladach
      method, but also had additional advantages, such as faster in delivering the
      fetus, less damage, easier mastering for obstetricians.

PMID- 11523257
TI  - The role of nitric oxide in hyperoxic lung injury in premature rats.
AB  - To investigate the role of nitric oxide (NO) in hyperoxic lung injury, the 3-day
      old preterm rats were randomly assigned to four groups: group I (hyperoxia
      group), group II (hyperoxia + Nw-nitro-L-arginine methyl ester (L-NAME) group),
      group III (air group), and group IV (air + L-NAME) group. Group I and II were
      exposed to > or = 90% O2 for 3 or 7 days. Group II and IV received subcutaneous L
      NAMEy on daily basis (20 mg/kg). After 3 day or 7 day exposure, the lung wet
      weight/dry weight ratio (W/D), total protein and malondialdehyde (MDA) in
      bronchoalveolar lavage fluid (BALF) and lung pathology were examined in all
      groups. NO content, expression of endothelial NOS (eNOS) and inducible NOS (iNOS)
      in lungs were measured in group I and III. Our results showed that after 3 day
      exposure, group I appeared acute lung injury characterized by the increase of MDA
      content (P < 0.01) and the presence of hyperaemia, red cell extravasation and
      inflammatory infiltration; after 7 day exposure, except MDA, total protein and
      W/D were also increased in comparison with group III (P < 0.01, 0.05),
      pathological changes were more severe than those after 3 day exposure. After 3
      and 7 day exposure, total protein in group II was significantly increased as
      compared with group I (P < 0.01 for both). The pulmonary acute inflammatory
      changes were more obvious in group II than in group I. Occasionally, mild
      hemorrhage was detected in the lungs of group IV. BALF protein content in group
      IV was higher than that in group III after 7 day exposure (P < 0.01). After 3 and
      7 day exposure, NO content in BALF were all significantly elevated in group I as
      compared with group III (P < 0.01 for all). In the lungs of group I, strong
      immunostaining for iNOS was observed in airway and alveolar epithelia,
      inflammatory cells, which were stronger than those in group III. Expression of
      iNOS in rats after 7 day hyperoxic exposure was stronger than that after 3 day
      exposure. Shortly after 7 day exposure, stronger immunostaining for eNOS in
      airway epithelia in group I than that in group III was seen. Our study suggested
      that treatment with L-NAME worsened acute hyperoxic lung injury in preterm rats
      and also had a deleterious effect on the rats exposed to air, indicating that
      endogenous nitric oxide may play a protective role in rats under both
      physiological and hyperoxic status. Hyperoxia can significantly upregulate the
      expression of iNOS and eNOS in inflammatory cells, epithelia in the lungs of
      preterm rats, promote NO generation, which suggests that endogenous NO may
      mediate the hyperoxic pulmonary damage. Over-stimulation of iNOS may contribute
      to the pathogenesis of hyperoxic lung injury. NO may have dual roles in pulmonary
      oxygen toxicity.

PMID- 11523258
TI  - Stability of human follicle-stimulating hormone receptor mRNA in stably
      transfected cells.
AB  - In order to assess the impact of mRNA degradation on steady state levels of
      follicle-stimulating hormone receptor (FSHR) mRNA and on regulation of FSHR gene
      expression, the stability and half-life of FSHR mRNA were determined in
      transfected cells expressing recombinant FSHR. Time-dependent changes in FSHR
      mRNA content were determined by nuclease protection-solution hybridization assay
      (NPA) or by qualitative reverse transcription-competitive polymerase chain
      reaction (RT-PCR) in cultured hFSHR-YI cells, cell lines stably transfected with
      a human FSHR cDNA. FSHR mRNA content remained constant during 8 h control
      incubations of hFSHR-Y1 cells (NPA, 2.9 +/- 0.3 micrograms/mg RNA; RT-PCR, 2.7 +/
      0.3 micrograms/mg RNA). Actinomycin D (ActD, 5 micrograms/ml) inhibited mRNA
      synthesis, as assessed by incorporation of [3 H]uridine into total RNA, by 90%
      within 1 h in hFSHR-Y1 cells. No effect of ActD on cellular morphology or
      viability was observed. ActD caused a time-dependent decrease in FSHR mRNA
      content in hFSHR-Y1 cell lines with a lag time of 1 h. There were no significant
      differences in the rate of FSHR mRNA degradation between the two methods of mRNA
      quantification. The half-life of hFSHR mRNA was 3.6 +/- 0.2 h by NPA and 3.1 +/-
      0.1 h by RT-PCR. The results indicated that degradation of mRNA was an important
      process in maintenance of steady state expression of the FSHR gene in cells
      stably expressing recombinant receptor.

PMID- 11523259
TI  - A study of toxicity of 5-fluorouracil on bovine trabecular meshwork cells in
      vitro.
AB  - In order to explore whether the conventional use of 5-fluorouracil (5-Fu) had any
      toxic effects on trabecular meshwork cells, bovine trabecular meshwork cells were
      cultured in vitro and exposed to 5-Fu at different concentrations. The cellular
      morphology, ultrastructure, mortality and phagocytosis were studied under light
      microscopy, transmission electron microscopy and methods of Wright's stain. It
      was found that the toxic effects of 5-Fu on the cells were in a dose-dependent
      mode. 1 x 10(-1) mg/ml of 5-Fu caused a large part of cells rounded up, while 1 x
      10(-2) mg/ml of the drug only a rough appearance of the cell surface. Exposure to
      1 x 10(-2) mg/ml of 5-Fu made mitochrone swollen and rough endoplasmic reticulum
      enlarged, with the cell mortality being 50.5%. The latex microspheres engulfed in
      cytoplasm in cells receiving 1 x 10(-1) and 1 x 10(-2) mg/ml of 5-Fu were
      significantly decreased as compared with those in the control group (P < 0.01).
      It was concluded that the safe concentration of 5-Fu on bovine trabecular
      meshwork cells was 1 x 10(-2) mg/ml and the conventional dosage of 5-Fu in
      clinical practice would not cause injury to trabecular meshwork cells.

PMID- 11523260
TI  - A study on the expression of interleukin (IL)-10 and IL-12 P35, P40 mRNA in the
      psoriatic lesions.
AB  - To investigate the possible role of interleukin (IL)-10 and IL-12 in the
      pathogenesis of psoriatic lesions and to supply theoretical basis for the gene
      therapy for psoriasis, the expression of IL-10 and IL-12 P35, P40 mRNA in 12
      cases of psoriatic lesions and 6 normal skin tissues was detected by using RT-PCR
      technique. The results showed that the expression of IL-10 mRNA in the psoriatic
      lesions was significantly lower than that in the normal skin tissues (P < 0.001).
      The expression of IL-12 P35 was positive both in the psoriatic lesions and in the
      normal skin tissues. IL-12 P40 mRNA was expressed positively only in the
      psoriatic lesions but negatively in the normal skin tissues. It was suggested
      that IL-12 might take an important role in the occurrence and progression of
      psoriasis, but IL-10 might have certain role in the regression of psoriasis.

PMID- 11523261
TI  - The educational enrollment of immigrant youth: a test of the segmented
      assimilation hypothesis.
AB  - An analysis of 1990 census data on the educational enrollment of 15- to 17-year
      old immigrants to the United States provides partial support for predictions from
      both the segmented-assimilation hypothesis and the immigrant optimism hypothesis.
      Most immigrant adolescents, especially from Asia, are as likely as their native
      born peers to be enrolled in high school, or more so. The "at-risk" immigrant
      youths with above-average levels of nonenrollment that are not reduced with
      longer exposure to American society are primarily of Hispanic Caribbean origins
      (from Puerto Rico, the Dominican Republic, and Cuba). Recent Mexican immigrants
      who arrived as teenagers have nonenrollment rates over 40%, but Mexican youths
      who arrived at younger ages are only somewhat less likely to be enrolled in
      school than are native-born Americans.

PMID- 11523262
TI  - Differences in the locational attainment of immigrant and native-born households
      with children in New York City.
AB  - In this paper we use a data set created especially for New York City to evaluate
      whether the locational attainment of households with children, as indicated by
      the context of the neighborhoods in which they live, varies by their immigrant
      status. In addition, we evaluate whether the relationship between immigrant
      status and neighborhood conditions varies by the householder's race/ethnicity.
      Overall, when compared with native-born households with children, immigrant
      households with children live in neighborhoods of lower quality, characterized by
      higher teenage fertility rates and higher percentages of students in local
      schools scoring below grade level in math and of persons receiving AFDC, but
      lower rates of juvenile detention. Further analyses, however, revealed that
      race/ethnicity is far more potent than immigrant status per se in predicting
      where households with children live.

PMID- 11523263
TI  - How enduring were the inequalities among European immigrant groups in the United
      States?
AB  - A long-standing and unresolved issue in the study of racial and ethnic groups
      concerns the persistence of initial inequalities among groups. Recently it has
      surfaced again in the study of U.S. immigrant groups, in George Borjas's (1994)
      claim that the human capital differences among early-twentieth-century immigrant
      groups are reflected in the relative socioeconomic achievements of their third
      generations. Reexamining this claim, we find that Borjas's analysis hinges on a
      series of problematic decisions, such as his inclusion of non-European groups as
      well as his failure to take ethnically mixed ancestry into account and to
      compensate for the weak correspondence in eastern Europe between ethnic ancestry
      and the national frontiers of the early 1900s. We replicate a portion of his
      analysis, correcting for these problems. Our results reveal no correspondence
      between the literacy of the first generation and the educational attainment of
      the third among European groups. Borjas's analysis seems to go farthest astray in
      including non-Europeans, especially Mexicans, because of the more systematic
      legal and social liabilities suffered by these groups.

PMID- 11523264
TI  - Long-run convergence of ethnic skill differentials, revisited.
AB  - In my original study, "Long-Run Convergence of Ethnic Skill Differentials," I
      concluded that the ethnic differentials introduced by the Great Migration seemed
      to persist into the second and third generations. Alba, Lutz, and Vesselinov
      argue that my study contained a number of conceptual and data problems, and
      conclude that the correlation between the skills of the first and the third
      generations disappears when these problems are taken into account. My reanalysis
      of the Alba et al. data, however, documents a stronger link between the skills of
      the first and the third generations than suggested by those authors.

PMID- 11523265
TI  - Immigration and males' earnings inequality in the regions of the United States.
AB  - In this paper I investigate the impact of recent immigration on males' earnings
      distributions in the major regions of the United States. I use six counterfactual
      scenarios to describe alternative regional skill distributions and wage
      structures for the population of natives and long-term immigrants in the absence
      of recent immigration. I find that immigration over the last three decades can
      account for a substantial portion of the variation in inequality across the
      regions. Recent immigration has contributed moderately to national growth in
      males' earnings inequality, primarily by changing the composition of the
      population.

PMID- 11523266
TI  - Immigrants' welfare use and opportunity for contact with co-ethnics.
AB  - In this article we examine the relationship between immigrants' welfare use and
      their social capital, using the 1990 census. We measure community social capital
      using contact with co-ethnics and co-ethnics' economic inactivity, and examine
      the use of AFDC and SSI in two subpopulations: single-mother families and elderly
      units. Major findings are that the effects of social capital differ between
      immigrant single-mother families and elderly units; the effects of social capital
      differ between the young-at-arrival elderly and the old-at-arrival elderly; and
      the process of AFDC use is similar for immigrants and for natives, whereas the
      process of SSI use is more complicated for immigrants than for natives.

PMID- 11523267
TI  - A model of destination-language acquisition: application to male immigrants in
      Canada.
AB  - We develop a model using human capital theory and an immigrant adjustment process
      to generate hypotheses on the acquisition of destination-language skills among
      immigrants. The model is tested for adult male immigrants in the 1991 Census of
      Canada. Use of English or French is greater, the younger the age at migration,
      the longer the duration of residence, the higher the educational attainment, the
      farther the country of origin from Canada, and the linguistically closer the
      mother tongue to English or French, and among those who are not refugees, those
      from a former British, French, or American colony, and those who live in an area
      where fewer people speak the respondent's mother tongue. The explanatory
      variables based on birthplace have behavioral interpretations and possess almost
      as much explanatory power as the birthplace dummy variables.

PMID- 11523268
TI  - Circular, invisible, and ambiguous migrants: components of difference in
      estimates of the number of unauthorized Mexican migrants in the United States.
AB  - Based on an equation that can be used with available data and that provides a
      basis for facilitating decomposition analyses, this research estimates that about
      2.54 million total (as opposed to enumerated) unauthorized Mexicans resided in
      the United States in 1996. Comparing this figure with an estimate of about 2.70
      million released by the U.S. Immigration and Naturalization Service (INS) during
      the 1990s, we find that the two estimates involve different assumptions about
      circular, invisible, and ambiguous migrants. Such differences not only can have
      important policy implications; they can also be sizable and can operate in
      opposite directions, as illustrated by findings from a components-of-difference
      analysis. The results are also extrapolated to 2000, and implications for 2000
      census counts are discussed.

PMID- 11523269
TI  - Changes in children's time with parents: United States, 1981-1997.
AB  - In this paper we examine changes in the time American children spent with their
      parents between 1981 and 1997, and the contribution to these changes made by
      shifting patterns of female labor force participation, family structure, and
      parental education. We decompose changes into the parts attributable to changes
      in demographic characteristics and the parts probably due to changes in behavior.
      In general, children's time with parents did not decrease over the period; in two
      parent families it increased substantially. Population-level changes in
      demographic characteristics exerted only small direct effects on the time
      children spent with parents.

PMID- 11523270
TI  - Sibling, peer, neighbor, and schoolmate correlations as indicators of the
      importance of context for adolescent development.
AB  - We use nationally representative data to calculate correlations in achievement
      and delinquency between genetically differentiated siblings within a family,
      between peers as defined by adolescents' "best friend" nominations, between
      schoolmates living in the same neighborhood, and between grademates within a
      school. We find the largest correlations between siblings, especially identical
      twins. Grademate and neighbor correlations are small. Peer-based correlations are
      considerably larger than grademate and neighbor correlations but not larger than
      most sibling correlations. The data suggest that family-based factors are several
      times more powerful than neighborhood and school contexts in affecting
      adolescents' achievement and behavior.

PMID- 11523271
TI  - Brain imaging and language processing--an introduction to special issue papers.

PMID- 11523272
TI  - Functional anatomy of speech perception and speech production: psycholinguistic
      implications.
AB  - This paper presents evidence for a new model of the functional anatomy of
      speech/language (Hickok & Poeppel, 2000) which has, at its core, three central
      claims: (1) Neural systems supporting the perception of sublexical aspects of
      speech are essentially bilaterally organized in posterior superior temporal lobe
      regions; (2) neural systems supporting the production of phonemic aspects of
      speech comprise a network of predominately left hemisphere systems which includes
      not only frontal regions, but also superior temporal lobe regions; and (3) the
      neural systems supporting speech perception and production partially overlap in
      left superior temporal lobe. This model, which postulates nonidentical but
      partially overlapping systems involved in the perception and production of
      speech, explains why psycho- and neurolinguistic evidence is mixed regarding the
      question of whether input and output phonological systems involve a common
      network or distinct networks.

PMID- 11523273
TI  - Syntactic, prosodic, and semantic processes in the brain: evidence from event
      related neuroimaging.
AB  - The neural network supporting aspects of syntactic, prosodic, and semantic
      information processing is specified on the basis of two experiments using
      functional magnetic resonance imaging (fMRI). In these two studies, the
      presence/absence of lexical-semantic and syntactic information is systematically
      varied in spoken language stimuli. Inferior frontal and temporal brain areas in
      the left and the right hemisphere are identified to support different aspects of
      auditory language processing. Two additional experiments using event-related
      brain potentials investigate the possible interaction of syntactic and prosodic
      information, on the one hand, and syntactic and semantic information, on the
      other. While the first two information types were shown to interact early during
      processing, the latter two information types do not. Implications for models of
      auditory language comprehension are discussed.

PMID- 11523274
TI  - What's different in second-language processing? Evidence from event-related brain
      potentials.
AB  - German sentences which were either correct, contained a selectional restriction
      violation, or a word category violation were presented auditorily to 16 native
      speakers of German (L1 group) and to 16 native speakers of Russian, who had
      learned German after the age of 10 (L2 group). Semantic violations elicited an
      N400 effect for both groups, but with a reduced amplitude and a longer peak
      latency in the L2 group. Compared to correct sentences, sentences with a phrase
      structure violation elicited an early anterior negativity followed by a broad
      centro-parietal positivity in native speakers. By contrast, there was no
      differential modulation of the early anterior negativity in the L2 group. A late
      positivity was also elicited in the second language learners, but it was slightly
      delayed compared to that shown by native speakers. This pattern is discussed in
      terms of different degrees of automaticity with respect to the subprocesses
      involved in sentence comprehension.

PMID- 11523275
TI  - Prosodic boundaries, comma rules, and brain responses: the closure positive shift
      in ERPs as a universal marker for prosodic phrasing in listeners and readers.
AB  - Just as the false comma in this sentence, shows punctuation can influence
      sentence processing considerably. Pauses and other prosodic cues in spoken
      language serve the same function of structuring the sentence in smaller phrases.
      However, surprisingly little effort has been spent on the question as to whether
      both phenomena rest on the same mechanism and whether they are equally efficient
      in guiding parsing decisions. In a recent study, we showed that auditory speech
      boundaries evoke a specific positive shift in the listeners' event-related brain
      potentials (ERPs) that indicates the sentence segmentation and resulting changes
      in the understanding of the utterance (Steinhauer et al., 1999a). Here, we
      present three ERP reading experiments demonstrating that the human brain
      processes commas in a similar manner and that comma perception depends crucially
      on the reader's individual punctuation habits. Main results of the study are: (1)
      Commas can determine initial parsing as efficiently as speech boundaries because
      they trigger the same prosodic phrasing covertly, although phonological
      representations seem to be activated to a lesser extent. (2) Independent of the
      input modality, this phrasing is reflected online by the same ERP component,
      namely the Closure Positive Shift (CPS). (3) Both behavioral and ERP data suggest
      that comma processing varies with the readers' idiosyncratic punctuation habits.
      (4) A combined auditory and visual ERP experiment shows that the CPS is also
      elicited both by delexicalized prosody and while subjects replicate prosodic
      boundaries during silent reading. (5) A comma-induced reversed garden path turned
      out to be much more difficult than the classical garden path. Implications for
      psycholinguistic models and future ERP research are discussed.

PMID- 11523276
TI  - Functional neuroimaging studies of syntactic processing.
AB  - This paper reviews studies of the functional neuroanatomy of syntactic processing
      using positron emission tomography (PET) and functional magnetic resonance
      imaging (fMRI), focusing on interpretability of studies and the model of
      functional neuroanatomy that emerges from existing work. It is argued that
      existing studies suggest a specialization for one aspect of syntactic processing
      in the left inferior frontal cortex in proficient language users, with
      variability in this localization across the entire population.

PMID- 11523277
TI  - Syntactic working memory and the establishment of filler-gap dependencies:
      insights from ERPs and fMRI.
AB  - In this contribution, we review an ERP experiment and an fMRI experiment which
      investigated the processing of German wh-questions. On the basis of the ERP
      results, we will discuss current models of sentence processing and resource
      distribution during sentence comprehension. We argue that there exists a separate
      cognitive or neural resource that supports syntactic working memory processes
      necessary for the temporary maintenance of syntactic information for the parser.
      In the context of wh-movement, such a memory component is necessary for
      establishing filler-gap dependencies. The data obtained from the fMRI experiment
      will be used to discuss the results of previous neuroimaging studies of sentence
      processing. It is claimed that syntactic working memory, rather than syntactic
      processing per se, is supported by Broca's Area.

PMID- 11523279
TI  - We're in this together. All of us are responsible and accountable for one another
      at work.

PMID- 11523281
TI  - Drug & alcohol testing. Screening for safety.

PMID- 11523278
TI  - An event-related fMRI study of syntactic and semantic violations.
AB  - We used event-related functional magnetic resonance imaging to identify brain
      regions involved in syntactic and semantic processing. Healthy adult males read
      well-formed sentences randomly intermixed with sentences which either contained
      violations of syntactic structure or were semantically implausible. Reading
      anomalous sentences, as compared to well-formed sentences, yielded distinct
      patterns of activation for the two violation types. Syntactic violations elicited
      significantly greater activation than semantic violations primarily in superior
      frontal cortex. Semantically incongruent sentences elicited greater activation
      than syntactic violations in the left hippocampal and parahippocampal gyri, the
      angular gyri bilaterally, the right middle temporal gyrus, and the left inferior
      frontal sulcus. These results demonstrate that syntactic and semantic processing
      result in nonidentical patterns of activation, including greater frontal
      engagement during syntactic processing and larger increases in temporal and
      temporo-parietal regions during semantic analyses.

PMID- 11523282
TI  - Drug & alcohol testing. Is your corporate culture on drugs?

PMID- 11523283
TI  - Drug & alcohol testing. Oral fluid testing update.

PMID- 11523284
TI  - Chemical protective clothing.

PMID- 11523285
TI  - Well suited for HAZMAT?

PMID- 11523286
TI  - Monday morning blues.

PMID- 11523287
TI  - Dressing for safety success.

PMID- 11523288
TI  - Confined spaces. Minimizing the hazards.

PMID- 11523289
TI  - Construction safety. High-wire safety.

PMID- 11523291
TI  - Continuity of care: a reconceptualization.
AB  - Although continuity of care is considered an essential feature of good health
      care, researchers have used and measured continuity in many different ways, and
      no clear conceptual framework links continuity to outcomes. This article of
      offers a reconceptualization and definition of continuity based on agency theory.
      It posits that the value of continuity is to reduce agency loss by decreasing
      information asymmetry and increasing goal alignment. Three decades of empirical
      literature on continuity were examined to assess whether this model would provide
      greater clarity about continuity. Some authors measured improved information
      transfer, but more appeared to assume that continuity would lead to better
      information. Most authors appeared to have assumed that goal alignment was
      present and did not measure it. The model of continuity based on agency theory
      appears to provide a useful conceptual tool for health services research and
      policy.

PMID- 11523292
TI  - Relocation of the elderly.
AB  - In this article, the author reviews 78 studies addressing the relocation of the
      elderly. He begins by defining the four major forms of relocation and describing
      the trends in the current health care marketplace precipitating relocation
      events. Next, he reviews the major findings of studies assessing the potential
      negative and positive outcomes of relocation. These outcomes include changes in
      mortality rates, morbidity, and psychological or social changes. In addition,
      factors associated with successful relocation are presented. Finally, the primary
      contribution of this article is that the author assesses the strengths and
      limitations of this prior literature and combines the research he reviews in an
      analytic model. This model helps show some opportunities for future research in
      the relocation of the elderly.

PMID- 11523293
TI  - Medicare fees and small area variations in breast-conserving surgery among
      elderly women.
AB  - This study used data from Medicare files, the American Hospital Association's
      Annual Survey of Hospitals, and the 1990 census to investigate whether Medicare
      fees for breast-conserving surgery (BCS) and mastectomy (MST) affected the rate
      of BCS across 799 3-digit ZIP code areas in 1994. The full model, which was based
      on the conceptual framework of the supply of and demand for different treatments,
      explained 51 percent of the variation in BCS rates. Medicare fees were
      statistically significant and had the hypothesized effects: a 10 percent higher
      BCS fee was associated with a 7 to 10 percent higher BCS rate, while a 10 percent
      higher MST fee was associated with a 2 to 3 percent lower proportion receiving
      BCS. Other significant economic variables were proximity to a radiation therapy
      hospital, a teaching hospital or a cancer center, and the percentage of elderly
      women with incomes below the poverty rate, which were negatively related to the
      BCS rate. Variations in age, race, and metropolitan populations had small or
      insignificant effects. The single most important was the percentage of cases with
      one or more comorbidities.

PMID- 11523294
TI  - Can earnings decline cause a retirement flight of physicians? Financial
      compensation and the decision to stay in practice.
AB  - The authors analyze the historical correlation between annual change in the
      population of inactive physicians and annual change in the real net income earned
      by the average physician per hour of patient care. For a sample of nine census
      divisions across 8 years (1986-1989 and 1994-1997), two regression models
      conclude with 99% confidence that a fall in net income increases the outflow of
      physicians from active practice. Regression coefficients estimate that a $1.00
      fall in hourly net income increases the population of inactive physicians by 1.46
      percent after a 2-year period. Based on 1999 population data, the authors project
      that an earnings decline of $10.00 per patient care hour motivates 11,000
      physicians to retire early. With projections of between 50,000 and 150,000 excess
      practitioners in the U.S. health care system, the analysis suggests that
      deterioration in financial compensation can erase part but not all of a physician
      surplus through early retirement.

PMID- 11523295
TI  - [Image of the month. Souvenir of a trip to new Pangea].

PMID- 11523296
TI  - [Multidisciplinary management of the obese patient: example from the Obesity
      Center at the University of Liege].
AB  - Obesity is a mulfactorial disease whose prevalence is progressively increasing.
      Ideally, it requires a multidisciplinary management by medical doctors,
      dieticians, psychologists and kinetherapists. The new "Centre de l'Obesite" at
      the University of Liege aims at fulfilling such objectives with: 1) a first
      outpatient visit including the simultaneous participation of an endocrinologist,
      a dietician and a psychologist; 2) a structured and individualized programme of
      physical rehabilitation; 3) an individualized management of obese subjects as in
      (hospital) and/or outpatients, using medical and/or surgical approaches; and 4)
      an opportunity to benefit of other specialized medical advices, if necessary, in
      order to increase both the efficacy and safety of the treatment. Owing to the
      increasing importance of obesity and the well-known difficulties to succeed in
      treating it, general practitioners should consider this new centre as a valuable
      help rather than a competitive structure for the management of their patients,
      especially those with severe or morbid obesity.

PMID- 11523297
TI  - [Clinical case of the month. Report of a case of antiphospholipid syndrome].
AB  - This article reports a case of Anton-Babinski syndrome, due to right middle
      cerebral artery thrombosis and attributed to a likely primary antiphospholipid
      syndrome. It is always difficult to diagnose the latter, especially in the case
      of our patient who had a past history of multiple venous thromboses but also a
      heterozygosity for the mutation of the factor V of Leyden. We reviewed the
      literature dedicated to the prothrombotic events linked to the presence of these
      antiphospholipid antibodies: the lupus anticoagulant and the anticardiolipin
      antibodies.

PMID- 11523298
TI  - [What is the role of aceclofenac in the therapeutic arsenal against chronic
      osteoarthritis pathologies?].
AB  - The aim of this article is to critically review the potential role of aceclofenac
      in the treatment of inflammatory pain and chronic osteoarticular disorder, based
      on its activity on the mediators of inflammation, its effect on cartilage
      remodeling and on the results of clinical studies comparing aceclofenac with
      other NSAIDs in these disorders. Aceclofenac has an outstanding anti-inflammatory
      profile, involving besides a classical inhibition of prostaglandins E2, a
      decrease in the expression of several cytokines including interleukin 1 and tumor
      necrosis factor alpha. It also inhibits activated oxygen species production and
      influences cells adhesion. Aceclofenac and its main metabolite, 4
      hydroxyaceclofenac, has positive effects on cartilage anabolism combined with
      modulating effect of matrix catabolism. Clinically, aceclofenac has been
      consistently shown to have a similar efficacy than that of widely marketed NSAIDs
      and a tolerance profile at least as good, if not better than the profile observed
      for other NSAIDs in the treatment of osteoarthritis, rheumatoid arthritis and
      ankylosing spondylitis. As of today, no head to head comparison between
      aceclofenac and coxibs have been performed, nor for efficacy neither for
      tolerance. The specific profile of aceclofenac makes this NSAID an interesting
      candidate for long-term treatment of chronic rheumatic disorders as well as for
      treatment of acute inflammatory episodes.

PMID- 11523299
TI  - [Allergic thrombocytopenia to heparin].
AB  - Various heparin preparations can induce an allergic reaction in certain patients.
      This results in a fall in platelet count and, paradoxically, thrombosis. This
      phenomenon is called heparin induced thrombocytopenia type 2 (HIT-2), and should
      be distinguished from the mild and usually asymptomatic non-immunologic
      thrombocytopenia, that often occurs during therapy with heparin (HIT-1). In HIT
      2, platelets counts fall by at least fifty per cent between the fifth and the
      fourteenth day of therapy. Immediate interruption of heparin administration is
      required. It is due to intense platelet activation by circulating immune
      complexes containing antibodies to the heparin-platelet factor 4 complex. These
      complexes cause damage to endothelial cells, which increases the risk of
      thrombosis. This risk persists over the subsequent weeks after cessation of
      heparin and the correction of platelet count. Anticoagulation must be maintained,
      often using recombinant hirudin, which is progressively replaced by oral anti
      vitamin K agents.

PMID- 11523300
TI  - [Venous and arterial thromboembolism in a patient with factor V R506Q Leiden
      mutation and heparin-induced immuno-allergic reaction].
AB  - A forty-six-year old in-patient was treated with heparin for massive pulmonary
      embolism. During the hospitalization, the clinical evolution was unusual and
      characterised as follows: a) the extent of pulmonary embolism justified a
      thrombolysis by streptokinase; b) an acute thrombocytopenia occurred a few days
      later, preceded by a slower, but significant decrease of platelet count; c) a non
      occlusive aortic thrombosis developed, distal to renal arteries, causing distal
      embolisation, successfully treated by local fibrinolysis. The prompt correction
      of platelet count after interruption of heparin therapy confirmed the diagnosis,
      before the detection of antibodies against heparin-PF4 complexes. Heparin was
      immediately replaced by another direct anticoagulant, recombinant hirudin
      (lepirudine-Refludan), initially given alone and progressively replaced by an
      antivitamin K (Sintrom). The occurrence of distal embolism from aortic
      thrombosis, developed during the critical period, characterizes this syndrome,
      which appears rare but whose incidence is probably underestimated. A subsequent
      investigation for risk factors for venous thromboembolism in this patient
      revealed a heterozygous mutation of the Leiden type factor V in our patient, and
      also in others family members.

PMID- 11523301
TI  - [Environmental illnesses, illnesses of the 21st century. Respiratory tract
      pathology and indoor air pollution].
AB  - Air pollution becomes a major concern in the 21st century. There is of course a
      relation between outdoor pollution and pollution in the building where we live
      and work. Indoor pollution, nevertheless is characterized by a higher
      concentration of several pollutants. This article is a short review of the main
      chemical and biological substances present in the indoor environment which may
      impair the lung health.

PMID- 11523302
TI  - [Shone's syndrome: report of four cases and review of the literature].
AB  - The observation of four clinical cases of Shone's complex, two of them presenting
      first with predominant coarctation of the aorta, prompted us to review the
      pertinent literature. Patients with multiobstructive lesions of the left heart,
      including Shone's complex, represent a surgical challenge where the adequate
      management of mitral valve anomalies, subaortic stenosis, and coarctation
      constitutes the key prognostic factor for satisfactory mid-term outcome.

PMID- 11523303
TI  - [Resurgence of vein perforation surgery: SEPS (subfacial endoscopic perforator
      surgery)].
AB  - The treatment of venous ulcers is a challenge even in this era of modern
      medicine. The role of incompetent perforating veins in the pathophysiology of
      venous ulcers has been well documented. Open surgical interruption of incompetent
      perforating veins (Linton's procedure) may be complicated by important wound
      healing problems, and has never gained widespread acceptance as a first choice
      treatment. Recently, an endoscopic technique of subfascial interruption of
      perforating veins has been developed. This new procedure, with smaller scars and
      faster recovery, gives promising midterm results. The authors summarize their
      initial experience with subfascial endoscopic perforating surgery (SEPS) during
      the last three years (25 cases). They obtained ulcer healing in all cases. At 16
      month follow-up, 88% of patients remain ulcer free. Three patients developed a
      new minor ulceration in the era of lipodermatosclerosis. This less invasive
      technique is a promising tool in the management of patients with venous ulcer
      disease.

PMID- 11523304
TI  - [Introduction to paleopathology. At the sources of cancers in the dinosaurs].
AB  - Cancers were present on earth well before man. The most ancient clues for such
      diseases have been found in fossils of dinosaurs.

PMID- 11523305
TI  - [Internet addiction: a different kind of addiction?].
AB  - The concept of Internet addiction, also called Internet addictive disorder or
      pathological Internet use, entered the medical dictionary in 1995. More and more
      authors have been preoccupied with it lately, and the majority conclude that this
      condition, on which some people cast doubt a few years ago, well and truly
      exists. Several forms of Internet addiction appear to exist, categorised
      according to the type of misuse it is subjected to: "cybersex", "chat rooms",
      "net gaming", the pathological search for information or video games being the
      most frequent. Psychiatric disorders most usually associated with Internet
      addiction seem to be bipolar disorders. As a consequence, efficient drugs would
      be those that act as thymo-stabilisers, undoubtedly because they are also
      effective against those bipolar disorders. Psychotherapeutic treatments as
      discussion groups on the Internet or group therapies have not yet been evaluated.

PMID- 11523306
TI  - [Autopharmacology, sloths and physiology. Opinions on certain historical aspects
      and potential developments in physiology in Liege].
AB  - We recall the works of Bacq, Lecomte and Goffart, three physiologists from the
      University of Liege, on neurohumoral transmission, autacoids, sloths and monkeys
      in order to stress first that Physiology is a natural science of its own, and
      secondly that physiological studies aim at the understanding of the general
      mechanisms concurring to homeostasis.

PMID- 11523307
TI  - [Info-congress. Insulin therapy for preventing type 1 diabetes in high-risk
      relatives: negative results of the "Diabetes Prevention Trial-Type 1"].
AB  - The results of the American multicentre "Diabetes Prevention Trial-Type 1" were
      presented by J. Skyler during the last congress of the American Diabetes
      Association in Philadelphia on June 23, 2001. The prophylactic subcutaneous
      administration of low-dose insulin was not able to prevent the development of
      type 1 diabetes nor to preserve residual insulin secretion in young relatives at
      very high-risk of diabetes (> 50% in the next 5 years), selected upon genetic,
      immunological and metabolic criteria.

PMID- 11523309
TI  - Subchronic studies on modulation of feeding behavior and body weight by
      neurosteroids in female mice.
AB  - Neurosteroids have shown promising therapeutic potential in a wide variety of
      neuropsychiatric and cognitive disorders. However, little research has been done
      on their role for the treatment of eating disorders and regulation of energy
      balance in the body. In the present study, subchronic treatment with the
      neuroactive steroid progesterone (10 mg/kg s.c.) for 28 days produced significant
      increases in body weight and elicited marked hyperphagia as compared to a vehicle
      treated control group at all time intervals as observed on days 1, 7, 14, 21 and
      28. On the other hand, subchronic treatment with dehydroepiandrosterone sulfate
      (DHEAS) for 28 days at 10 mg/kg s.c. produced significant (p < 0.05) decreases in
      body weight and food intake at all time intervals on days 1, 7, 14 and 28
      suggesting that decreases in food intake are responsible for the reduction of
      body weight caused by DHEAS in this strain of female mice. Subchronic treatment
      with DHEAS (10 mg/kg s.c.) also significantly (p < 0.05) suppressed progesterone
      induced weight gain and hyperphagia as compared to the progesterone-treated group
      but not as compared to the vehicle-treated control group (except on day 1). In
      conclusion, the results of the present study suggest that progesterone-induced
      hyperphagia and weight gain can serve as a useful animal model of drug-induced
      obesity. The drugs useful in this model may have implications for the treatment
      of obesity caused by disturbances of ovarian hormone secretion in females.
      Furthermore, the study underscores the use of these neurosteroids for the
      treatment of eating disorders.

PMID- 11523308
TI  - Protein kinase inhibition exerts cardioprotective effects in myocardial
      ischemia/reperfusion via inhibition of superoxide release.
AB  - Staurosporine, a selective inhibitor of protein kinase C (PKC) in the low
      nanomolar range suppresses superoxide production from polymorphonuclear
      leukocytes (PMNs). Therefore, we hypothesized that staurosporine could attenuate
      PMN-induced cardiac dysfunction by inhibiting superoxide production from PMNs. We
      examined the effects of staurosporine in isolated ischemic (I) (20 min) and
      reperfused (R) (45 min) rat hearts perfused with PMNs. Staurosporine given at 5
      or 20 nM to hearts at R significantly improved left ventricular developed
      pressure (LVDP) (p < 0.01) and the maximal rate of development of LVDP
      (+dP/dtmax) (p < 0.05, 5 nM, and p < 0.01, 20 nM) compared to similar hearts
      perfused in the absence of staurosporine. Recombinant human superoxide dismutase
      (hSOD, 4 micrograms/ml) restored LVDP and +dP/dtmax to that of initial baseline
      at 45 min postreperfusion. Staurosporine also significantly reduced PMN adherence
      to the endothelium and infiltration into the myocardium by 38 to 48% (p < 0.01),
      whereas hSOD attenuated PMN infiltration and adherence by 74% (p < 0.001). These
      results provide clear evidence that inhibition or scavenging of superoxide
      release from PMNs significantly attenuates PMN-induced cardiac contractile
      dysfunction in the ischemic-reperfused rat heart and that a significant component
      of superoxide release from PMNs is mediated by PKC.

PMID- 11523311
TI  - Effects of lisinopril on streptozotocin-induced diabetic neuropathy in rats.
AB  - Streptozotocin (STZ)-induced diabetic neuropathy in rats was monitored by
      measuring the motor nerve conduction velocity (MNCV) and histopathology of the
      tibial nerve. Pretreatment with lisinopril (2 mg/kg p.o., 5 days prior to STZ and
      continued for 10 weeks) significantly (p < 0.01) prevented deterioration of MNCV
      as compared to STZ-diabetic animals. Nerve sections from the lisinopril
      pretreated group revealed less structural damage as compared to STZ-diabetic
      rats. However lisinopril had no effect on blood sugar, i.e., it did not alter the
      diabetic state. It is concluded that lisinopril prevents the development of
      experimental diabetic neuropathy in STZ-induced diabetic rats.

PMID- 11523310
TI  - Dietary supplementation of the pyridoindole antioxidant stobadine reduces
      vascular impairment in streptozotocin-diabetic rats.
AB  - We studied the influence of hyperglycemia lasting 1, 4, 6 and 8 months on the
      reactivity and ultrastructure of the aorta in Wistar rats. Moreover, the effect
      of the pyridoindole antioxidant stobadine ((-)-cis-2,8-dimethyl-2,3,4,4a,5,9b
      hexahydro-1H-pyrido[4,3-b]indole) on the changes induced by the 8-month
      hyperglycemia were studied. Hyperglycemia was induced by streptozotocin (STZ, 55
      mg/kg i.v.). In the functional study, responses to KCl, acetylcholine (ACh),
      noradrenaline (NA) and hydrogen peroxide were evaluated under isometric
      conditions. The first changes in aortic reactivity started after 1 month of
      hyperglycemia and were exhibited by significantly increased NA-induced
      contractions. Relaxant responses to acetylcholine were decreased, although not
      significantly. Prolongation of hyperglycemia to 4, 6 and 8 months did not cause
      any additional significant changes in responsiveness to NA. Decreased ACh-induced
      relaxation and increased contractile responses to H2O2 were observed in month 4.
      The functional responses were not substantially deteriorated by prolongation of
      hyperglycemia to 6 and 8 months. Ultrastructural examination of the diabetic
      aorta showed disturbances in normal tissue organization. An 8-month
      supplementation of stobadine in diabetic rats resulted in the protection of
      aortic function as well as its ultrastructure. These results suggest that
      abnormalities occurring in the aorta of diabetic rats might result from the
      damaging effects of oxygen free radicals.

PMID- 11523312
TI  - Continuous UVB irradiation to modify the biophysical properties and protein
      conformation of rat skin.
AB  - In order to determine the continuous irradiation effects of UVB on the skin of
      live Sprague Dawley (SD) rats, the changes in biophysical properties and protein
      conformation of the skin were studied. The continuous UVB irradiation affecting
      the water content, skin color and protein structure of the rat skin was
      investigated by using a skin surface hygrometer, a Chroma meter and an attenuated
      total reflection (ATR)/Fourier transform infrared (FT-IR) spectroscopy. Test
      areas on the dorsal skin were continuously irradiated with 600 +/- 10 microW/cm2
      UVB for 56 h. Part of the dorsal skin was covered with a bandage as a non
      irradiated control. The results indicated that the water content of the
      irradiated skin decreased with UVB irradiation, but the non-irradiated control
      skin exhibited a higher level of water content. The decrease in the skin's water
      binding capacity from cracks induced by continuous UVB irradiation, and the
      occlusive dressing of the non-irradiated skin to prevent water loss and form full
      hydration might be responsible for the results. The decrease of L* value and the
      increase in a*, b* and delta E values in the skin color parameters with UVB
      irradiation indicates an incremental darkening of the skin and a marked increase
      in erythema. However, there was no significant change in skin color for the non
      irradiated control skin. A slight modification of the protein secondary structure
      in the skin after continuous UVB irradiation was also evidenced by transforming
      the alpha-helix structure into a beta-sheet structure after long-term continuous
      UVB irradiation. Continuous UVB irradiation of SD rat skin may decrease the
      skin's water-binding capacity, cause darkening, increase erythema and modify the
      protein secondary structure of the skin.

PMID- 11523313
TI  - Acute hemodynamic effects during immunoadsorption in patients with dilated
      cardiomyopathy positive for beta 1-adrenoceptor autoantibodies.
AB  - In two recent studies immunoadsorption improved left ventricular function in
      patients with dilated cardiomyopathy (DCM) who were positive for
      cardiostimulatory autoantibodies against the human beta 1-adrenoceptor (beta 1
      AAB). In this study we invasively measured acute hemodynamics during
      immunoadsorption. Three patients with DCM, who were positive for beta 1-AAB (NYHA
      class III, left ventricular ejection fraction < 0.3), were treated with 1
      immunoadsorption session daily on 5 consecutive days. Immunoadsorption induced a
      strong decrease of cardiac index, whereas systemic vascular resistance increased.
      Baseline levels were reached again several hours after therapy ended. We conclude
      that during immunoadsorption substantial hemodynamic changes occur in patients
      positive for beta 1-AAB.

PMID- 11523314
TI  - Phenotype of cytochrome P450 CYP2D6 in patients with familial adenomatous
      polyposis.
AB  - This paper describes an attempt to establish the distribution of the oxidative
      phenotype of sparteine in patients with familial adenomatous polyposis (FAP). The
      oxidative polymorphism of sparteine was determined in 30 patients with FAP. One
      hundred and twenty-six normal subjects were examined as a control group. Subjects
      with urinary metabolic ratios (MR) greater than 20 (the metabolic ratio of
      sparteine/dehydrosparteines excreted in urine) were defined as poor metabolizers
      of sparteine. None of the patients were classified as poor metabolizers of
      sparteine, although 5 control subjects were. No significant differences were
      found in the distribution of frequencies between patients and control subjects.
      However, there was a higher metabolic ratio (mean 1.58 +/- 1.13) in 5 patients
      with malignant changes in large bowel adenomas compared with other FAP patients
      without malignant changes (mean MR 0.89 +/- 0.66).

PMID- 11523315
TI  - Long-term treatment with enalapril or losartan does not show antiproliferative
      effects in peripheral blood mononuclear cells.
AB  - The objective of this study was to evaluate the long-term effects of enalapril,
      an angiotensin-converting enzyme inhibitor, and losartan, an angiotensin type 1
      receptor antagonist, on the proliferation of peripheral blood mononuclear cells
      (PBMC) in patients with essential hypertension. Nine patients with a sitting
      diastolic blood pressure of > 95 mmHg and < 105 mmHg at the end of a 4-week
      placebo run-in period entered the double-blind phase of the study, which
      consisted of three 6-week periods during which patients were treated with
      placebo, enalapril (20 mg o.d.) or losartan (50 mg o.d.) The de novo synthesis of
      DNA, RNA and protein in PBMC was measured by [3H]-thymidine, [3H]-uridine or [3H]
      leucine incorporation, respectively. Neither enalapril nor losartan affected the
      proliferation of PBMC measured as de novo synthesis of DNA, RNA and protein. Our
      data show that proliferation was not affected during angiotensin-converting
      enzyme inhibition with enalapril and angiotensin receptor type 1 antagonism with
      losartan.

PMID- 11523317
TI  - The way in which intervention studies have "personality" and why it is important
      to meta-analysis.
AB  - Intervention studies represent webs of interrelated substantive and
      methodological characteristics that take on different patterns in different
      studies and different intervention areas. All too often, meta-analysts do not
      give close attention to the possibility that these interrelated differences among
      studies are related in complex ways to study effect sizes and, consequently, run
      considerable risk of reporting results that are misleading or flatly wrong. To
      remedy this situation, improvements are needed in both the method and practice of
      meta-analysis so that greater attention can be given to effect size variation,
      the generalizability of study results, and the systematic multivariate
      relationships between study characteristics and the effect sizes reported in
      those studies.

PMID- 11523316
TI  - Effect of short-term losartan treatment in patients with primary aldosteronism
      and essential hypertension.
AB  - The aim of this study was to investigate the effect of short-term treatment with
      losartan, a selective and competitive angiotensin II (AngII) receptor blocker, on
      vascular endothelial growth factor (VEGF), active renin and kallikrein activity
      (KA) in patients with essential hypertension and primary aldosteronism. Nine
      patients with primary aldosteronism (5 with Conn adenoma and 4 with idiopathic
      hyperaldosteronism) and 9 patients with essential hypertension were included in
      the study. Systolic and diastolic blood pressure decreased significantly after
      losartan treatment in both patient groups. Plasma and urinary Kallikrein activity
      were significantly higher in primary aldosteronism in comparison with essential
      hypertension. There were no significant changes in the active renin and
      aldosterone in patients with primary aldosteronism after treatment. Plasma and
      urinary KA decreased significantly after losartan administration in both groups.
      Serum VEGF levels in primary aldosteronism were not significantly different from
      those in essential hypertension and did not change significantly after treatment
      in either group. In conclusion, losartan, in usual therapeutic doses, lowers
      blood pressure in patients with primary aldosteronism and essential hypertension.
      This marked antihypertensive effect in primary aldosteronism could be explained
      predominantly by blockade of tissue renin-angiotensin system (RAS). The
      variations in KA could be due to hemodynamic changes. VEGF is not likely to be
      involved in the action of losartan.

PMID- 11523318
TI  - Conducting meta-analyses of HIV prevention literatures from a theory-testing
      perspective.
AB  - Using illustrations from HIV prevention research, the current article advocates
      approaching meta-analysis as a theory-testing scientific method rather than as
      merely a set of rules for quantitative analysis. Like other scientific methods,
      meta-analysis has central concerns with internal, external, and construct
      validity. The focus of a meta-analysis should only rarely be merely describing
      the effects of health promotion, but rather should be on understanding and
      explaining phenomena and the processes underlying them. The methodological
      decisions meta-analysts make in conducting reviews should be guided by a
      consideration of the underlying goals of the review (e.g., simply effect size
      estimation or, preferably theory testing). From the advocated perspective that a
      health behavior meta-analyst should test theory, the authors present a number of
      issues to be considered during the conduct of meta-analyses.

PMID- 11523319
TI  - Missing predictors in models of effect size.
AB  - Missing data occur frequently in meta-analysis. Reviewers inevitably face
      decisions about how to handle missing data, especially when predictors in a model
      of effect size are missing from some of the identified studies. Commonly used
      methods for missing data such as complete case analysis and mean substitution
      often yield biased estimates. This article briefly reviews the particular
      problems missing predictors cause in a meta-analysis, discusses the properties of
      commonly used missing data methods, and provides suggestions for ways to handle
      missing predictors when estimating effect size models. Maximum likelihood methods
      for multivariate normal data and multiple imputation hold the most promise for
      handling missing predictors in meta-analysis. These two model-based methods apply
      to a broad set of data situations, are based on sound statistical theory, and
      utilize all information available to obtain efficient estimators.

PMID- 11523320
TI  - From the general to the specific. Using meta-analytic reports in clinical
      decision making.
AB  - The purpose of this article is to describe how health practitioners can interpret
      the results from published meta-analytic reports of intervention effectiveness
      and efficacy studies, and then communicate those results, in a manner that helps
      patients make critical clinical and life decisions. The problem of using research
      evidence in clinical decision making is one of moving from generalized findings
      about intervention effectiveness to a prediction for a specific patient. To move
      toward a reasonable prediction, practitioners need information from a meta
      analytic report that enables them to identify and understand the distribution of
      outcome results that are most applicable to a specific patient. Relevancy,
      effectiveness, and interpretation forms of information are discussed in this
      article. The focus is on the interpretation of the effect size statistics d and r
      for understanding the variation in responses that the patient might experience
      with an intervention.

PMID- 11523321
TI  - The growth of health-related meta-analyses published from 1980 to 2000.
AB  - A MEDLINE search was conducted to estimate trends in the growth of health-related
      meta-analyses published during the past two decades. Employing a more specific
      than sensitive search strategy, and not supplementing these results with known
      sources of published meta-analyses or manual search strategies, 3,025 probable
      meta-analyses were selected from the 5,128 citations identified. The data showed
      a definitive upward (and generally linear) trend across time with no evidence for
      this genre of research either leveling off or decreasing.

PMID- 11523322
TI  - Evaluation of alcohol education programs on attitude, knowledge, and self
      reported behavior of college students.
AB  - This research was conducted as a pilot study to evaluate the effectiveness of two
      different types of alcohol education programs for college students. The
      educational programs were a teacher-centered motivational speech and "Alcohol
      101," a new student-centered CD-ROM interactive program. The research was
      conducted at a public university in the Northeastern United States. A
      pretest/posttest quasi-experimental control group design was used. The instrument
      used was the Student Alcohol Questionnaire (SAQ). Univariate analysis of
      covariance was used to test for postintervention differences across groups for
      attitudes and knowledge about alcohol and self-reported alcohol consumption
      behavior. A statistically significant difference between groups for the second
      postintervention measure of attitude was identified. No significant differences
      in knowledge that could be attributed to the interventions were found, and no
      statistically significant differences were found for self-reported behavior.

PMID- 11523323
TI  - Use of tree rings to investigate the onset of contamination of a shallow aquifer
      by chlorinated hydrocarbons.
AB  - Oaks (Quercus velutina Lam.) growing over a shallow aquifer contaminated by
      chlorinated hydrocarbons were studied to determine if it was possible to estimate
      the approximate year that contamination began. The annual rings of some trees
      downgradient from the contaminant release site contained elevated concentrations
      of chloride possibly derived from dechlorination of contaminants. Additionally, a
      radial-growth decline began in these trees at approximately the same time that
      chloride became elevated. Growth did not decline in trees that contained smaller
      concentrations of chloride. The source of elevated chloride and the corresponding
      reductions in tree growth could not be explained by factors other than
      contamination. On the basis of tree-ring evidence alone, the release occurred in
      the late 1960s or early 1970s. Contaminant release at a second location
      apparently occurred in the mid- to late 1970s, suggesting that the area was used
      for disposal for at least 5 years and possibly longer.

PMID- 11523324
TI  - Impact of urbanization on hydrochemical evolution of groundwater and on
      unsaturated-zone gas composition in the coastal city of Tel Aviv, Israel.
AB  - The coastal city of Tel Aviv was founded at the beginning of the 20th century.
      The number of its inhabitants and its water consumption increased rapidly. This
      study analyses a 15-year record (1934-1948) of pre-industrial development of
      groundwater chemistry in the urban area. Archive data on concentrations of major
      ions, dissolved gases (CO2 and O2), organic matter, and pH were available for
      each half-year during the period of 1934-1948. The major factors causing changes
      in the chemistry of groundwater flowing in three sandy sub-aquifers have been
      seawater encroachment due to overpumping, and infiltration of effluents from pit
      latrine collectors. Influence of these factors decreases with depth. Landward
      penetrating seawater passed through clayey coastal sediments, interbedded among
      sands and calcareous sandstones, and spread into the Kurkar Group aquifer. This
      has led to exchange of sodium (dominant in seawater) with calcium adsorbed on
      clay particles, enriching groundwater with calcium. Intensity of cation exchange
      decreases inland and with depth. Infiltration of pit-latrine effluents has
      introduced large amounts of ammonium into the unsaturated zone. Its rapid
      oxidation in unsaturated sediments has caused massive nitrate production,
      accompanied by pore-water acidification. This process induces dissolution of
      vadose carbonate, resulting in enrichment of groundwater recharge in calcium.
      Anthropogenically induced dissolution of calcite in the unsaturated zone has been
      the major factor for the increase of Ca2+ concentration in groundwater,
      accounting for about 80% of this increase. In the interface zone, an additional
      20% of calcium has been supplied by cation exchange. Owing to pH increase caused
      by denitrification in the aquifer, Ca(2+)-rich waters supersaturated with calcite
      could be formed, especially in the capillary fringe of the uppermost sub-aquifer,
      which could induce calcite precipitation and ultimately lead to the cementation
      of sandy aquifers. Urban development has caused drastic changes in the gas
      content in the unsaturated zone and in groundwater. Carbon dioxide was
      intensively generated by nitrification-denitrification processes, by hydration of
      urea, to a lesser degree by oxidation of organic matter, and probably by anoxic
      biodegradation of organics. Between 1934 and 1948, concentrations of CO2 in
      unsaturated sediment air rose from 3.2% to 7.6%. In the unsaturated zone, oxygen
      consumption for oxidation of ammonium and organic matter lowered O2
      concentrations in sediment air to unusually low values of 3.9-12.9%.
      Nitrification in the urban unsaturated zone could thus serve as a pump, sucking
      in atmospheric oxygen at a rate of about 0.3-0.5 g m-2 day-1. The extreme
      concentrations of CO2 and O2 in unsaturated sediments have been preserved due to
      production and consumption of gas under conditions of diminishing areas open to
      the atmosphere, uncovered by buildings and by roads.

PMID- 11523325
TI  - Biodegradation during contaminant transport in porous media: 3. Apparent
      condition-dependency of growth-related coefficients.
AB  - The biodegradation of organic contaminants in the subsurface has become a major
      focus of attention, in part, due to the tremendous interest in applying in situ
      biodegradation and natural attenuation approaches for site remediation. The
      biodegradation and transport of contaminants is influenced by a combination of
      microbial and physicochemical properties and processes. The purpose of this paper
      is to investigate the impact of hydrodynamic residence time, substrate
      concentration, and growth-related factors on the simulation of contaminant
      biodegradation and transport, with a specific focus on potentially condition
      dependent growth coefficients. Two sets of data from miscible-displacement
      experiments, performed with different residence times and initial solute
      concentrations, were simulated using a transport model that includes
      biodegradation described by the Monod nonlinear equations and which incorporates
      microbial growth and oxygen limitation. Two variations of the model were used,
      one wherein metabolic lag and cell transport are explicitly accounted for, and
      one wherein they are not. The magnitude of the maximum specific growth rates
      obtained from calibration of the column-experiment results using the simpler
      model exhibits dependency on pore-water velocity and initial substrate
      concentration (C0) for most cases. Specifically, the magnitude of micron
      generally increases with increasing pore-water velocity for a specific C0, and
      increases with decreasing C0 for a specific pore-water velocity. Conversely, use
      of the model wherein observed lag and cell elution are explicitly accounted for
      produces growth coefficients that are similar, both to each other and to the
      batch-measured value. These results illustrate the potential condition-dependency
      of calibrated coefficients obtained from the use of models that do not account
      explicitly for all pertinent processes influencing transport of reactive solutes.

PMID- 11523327
TI  - Non-aqueous-phase-liquid breakthrough during evaporative drying of clay barriers.
AB  - In this study, an attempt has been made to model a real field scenario, whereby
      an initially almost saturated clay liner in a waste site is gradually drying, due
      to evaporation at its lower boundary. A detailed conceptual model that deals with
      the penetration and breakthrough of non-aqueous-phase-liquid (NAPL) in clay
      liners is introduced. Water content of clay samples was monitored during ambient
      evaporation through apertures at the base of sample holders. Clay drying rate
      served as the primary parameter for the NAPL breakthrough study. The
      interconnection between drying rates, structural damage formation (cracks and
      suction) and NAPL penetration is especially addressed. The processes taking place
      in the clay samples during drying appear to be associated with the capillary
      effects between the different fluid phases in the vicinity of either the NAPL
      clay or the clay-air boundaries. A conceptual model of NAPL penetration and
      breakthrough of the clay layer has been considered, based on both indirect and
      direct observations of structural damages produced on either clay boundaries. A
      mutual interaction between these two boundaries is suggested and discussed. NAPL
      breakthrough is suggested to take place through cracks initiated on the upper
      soil surface.

PMID- 11523326
TI  - Biodegradation during contaminant transport in porous media: 4. Impact of
      microbial lag and bacterial cell growth.
AB  - Miscible-displacement experiments were conducted to examine the impact of
      microbial lag and bacterial cell growth on the transport of salicylate, a model
      hydrocarbon compound. The impacts of these processes were examined separately, as
      well as jointly, to determine their relative effects on biodegradation dynamics.
      For each experiment, a column was packed with porous medium that was first
      inoculated with bacteria that contained the NAH plasmid encoding genes for the
      degradation of naphthalene and salicylate, and then subjected to a step input of
      salicylate solution. The transport behavior of salicylate was non-steady for all
      cases examined, and was clearly influenced by a delay (lag) in the onset of
      biodegradation. This microbial lag, which was consistent with the results of
      batch experiments, is attributed to the induction and synthesis of the enzymes
      required for biodegradation of salicylate. The effect of microbial lag on
      salicylate transport was eliminated by exposing the column to two successive
      pulses of salicylate, thereby allowing the cells to acclimate to the carbon
      source during the first pulse. Elimination of microbial lag effects allowed the
      impact of bacterial growth on salicylate transport to be quantified, which was
      accomplished by determining a cell mass balance. Conversely, the impact of
      microbial lag was further investigated by performing a similar double-pulse
      experiment under no-growth conditions. Significant cell elution was observed and
      quantified for all conditions/systems. The results of these experiments allowed
      us to differentiate the effects associated with microbial lag and growth, two
      coupled processes whose impacts on the biodegradation and transport of
      contaminants can be difficult to distinguish.

PMID- 11523328
TI  - Numerical analysis of biological clogging in two-dimensional sand box
      experiments.
AB  - Two-dimensional models for biological clogging and sorptive trace transport were
      used to study the progress of clogging in a sand box experiment. The sand box had
      been inoculated with a strip of bacteria and exposed to a continuous injection of
      nitrate and acetate. Brilliant Blue was regularly injected during the clogging
      experiment and digital images of the tracer movement had been converted to
      concentration maps using an image analysis. The calibration of the models to the
      Brilliant Blue observations shows that Brilliant Blue has a solid biomass
      dependent sorption that is not compliant with the assumed linear constant Kd
      behaviour. It is demonstrated that the dimensionality of sand box experiments in
      comparison to column experiments results in a much lower reduction in hydraulic
      conductivity (factor of 100) and that the bulk hydraulic conductivity of the sand
      box decreased only slightly. However, in the central parts of the clogged area,
      the observations and simulations clearly show a complex picture of flow diverting
      the injected nutrients around the clogged area as fingers. The calibration of the
      model demonstrates that the physical and microbiological processes (advection,
      dispersion, attachment-detachment, growth-decay) are all needed to capture the
      progress of clogging.

PMID- 11523329
TI  - Effect of surface coatings, grain size, and ionic strength on the maximum
      attainable coverage of bacteria on sand surfaces.
AB  - The injection of bacteria in the subsurface has been identified as a potential
      method for in situ cleanup of contaminated aquifers. For high bacterial loadings,
      the presence of previously deposited bacteria can result in decreased deposition
      rates--a phenomenon known as blocking. Miscible displacement experiments were
      performed on short sand columns (approximately 5 cm) to determine how bacterial
      deposition on positively charged metal-oxyhydroxide-coated sands is affected by
      the presence of previously deposited bacteria. Approximately 8 pore volumes of a
      radiolabeled bacterial suspension at a concentration of approximately 1 x 10(9)
      cells ml-1 were introduced into the columns followed by a 2-pore-volume flush of
      cell-free buffer. It was found that the presence of Al- and Fe-coated sand
      increased both deposition rates and maximum fractional surface coverage of
      bacteria on the sediment surfaces. The effect of grain size on maximum bacterial
      retention capacity, however, was not significant. Decreasing ionic strength from
      10(-1) to 10(-2) M KCl resulted in noticeable decreases in sticking efficiency
      (alpha) and maximum surface coverage (thetamax) for clean silica sand--results
      consistent with DLVO theory. In columns containing positively charged Al- and Fe
      coated sands, however, changes in alpha and thetamax due to decreasing ionic
      strength were minimal. These findings demonstrate the importance of geochemical
      controls on the maximum bacterial retention capacity of sands.

PMID- 11523330
TI  - Measuring supportive and unsupportive responses during cancer treatment: a factor
      analytic assessment of the partner responses to cancer inventory.
AB  - This study examined the psychometric structure of a measure of positive and
      negative spouse responses to individuals with cancer, the Partner Responses to
      Cancer Inventory (PRCI). The forty-eight items were either developed by the
      authors or adapted from the Inventory of Socially Supportive Behaviors. Seven a
      priori subscales of the PRCI, four positive support scales and three negative
      spouse behavior scales, were hypothesized. The instrument was administered to 304
      cancer patients undergoing cancer treatment. Exploratory factor analyses yielded
      four factors that were subsequently confirmed by confirmatory factor analysis:
      (a) Emotional and Instrumental Support, (b) Cognitive Information and Guidance,
      (c) Encouraging Distancing and Self-Restraint, and (d) Criticism and Withdrawal.
      The measure satisfied standard criteria for internal consistency and construct
      validity, and thus may be useful for social support theory and research.

PMID- 11523331
TI  - Perceived stress and cellular immunity: when coping counts.
AB  - This cross-sectional study investigated whether active and avoidance coping
      methods were differentially related to immune function depending on stress level.
      Perceived stress and coping method were assessed in 173 healthy older adults and
      related to the number and percentage of CD3+, CD4+, and CD8+ T lymphocytes as
      well as the proliferative response of peripheral blood leukocytes to
      phytohemagluttinin (PHA) and concanavalin A (Con A). Both active and avoidance
      coping significantly interacted with perceived stress on proliferative responses
      to both mitogens. Higher levels of active coping were significantly related to a
      more vigorous proliferative response to PHA and Con A, particularly at high
      stress levels. At low stress levels, active coping was not significantly related
      to proliferative responses, whereas avoidance coping was significantly associated
      with a greater proliferative response to Con A. These results suggest that the
      relationships between certain coping methods and immune function depend on
      perceived stress level.

PMID- 11523332
TI  - Long-term efficacy of biobehavioral treatment of temporomandibular disorders.
AB  - This study evaluated the relative long-term efficacy of biofeedback, cognitive
      behavioral skills training (CBST), combined biofeedback and CBST (Combined), and
      no-treatment comparison groups in 108 patients suffering from chronic
      temporomandibular disorder (TMD). After an initial evaluation, patients were
      assigned to one of the four treatment conditions. The three biobehavioral
      treatment interventions consisted of 12 standardized sessions. Patients were
      reevaluated 1 year after completing treatment. Results demonstrated that patients
      who received the biobehavioral treatments reported significant improvement in
      subjective pain, pain-related disability, and mandibular functioning 1 year after
      receiving treatment. The no-treatment comparison group did not demonstrate such
      improvements. The combined biofeedback and CBST treatment produced the most
      comprehensive improvements across all outcome measures. These results again
      demonstrate the heuristic value of adopting a biopsychosocial perspective to the
      assessment and treatment of chronic medical/dental disorders such as TMD.

PMID- 11523335
TI  - Management of new-onset atrial fibrillation.

PMID- 11523334
TI  - Gender and alcohol use: the roles of social support, chronic illness, and
      psychological well-being.
AB  - Men and women differ in their use of alcohol, in their rates of chronic illnesses
      and psychological symptoms, and in the social support they receive. In this
      paper, we assess how the latter three factors are associated with alcohol use,
      and how these associations differ by gender. Respondents were 3,074 male and
      3,947 female randomly selected Health Maintenance Organization members who
      responded to a mail survey in 1990. Hierarchical multiple regression analyses
      indicate that social support is associated with alcohol consumption in similar
      ways for both genders, yet the associations between some demographic, physical
      health/functioning, and psychological well-being measures are different for men
      and women. Men with fewer role limits due to physical health drank more, while
      women with better psychological well-being drank less. Poor psychological well
      being may be a modifiable risk factor for increased alcohol use among women;
      practitioners should be alert for greater consumption among men with few
      functional limitations and good health.

PMID- 11523336
TI  - The danger of bacterial meningitis in the adult. 1.

PMID- 11523333
TI  - Heterogeneity in the social networks of young and older adults: prediction of
      mental health and cardiovascular reactivity during acute stress.
AB  - We examined the utility of a broad framework that separated positive, negative,
      and ambivalent social network members. One hundred thirty-three young and older
      participants completed the social relationships index, measures of mental health,
      and a cardiovascular reactivity protocol. Results replicated prior research on
      the beneficial influence of positive (supportive) ties on psychological outcomes.
      More important, analyses also revealed that the number of ambivalent network ties
      predicted age-related differences in depression and sympathetic control of heart
      rate reactivity during stress. The statistical interactions between age and
      ambivalent ties on cardiovascular responses during stress were not changed when
      statistically controlling for other social network categories, demographic
      variables, and various personality factors. These data suggest that social
      network ambivalence was a relatively unique predictor of cardiovascular
      reactivity and highlight the utility of separating the variance due to positive,
      negative, and ambivalent network ties. Implications for the study of social
      relationships, physiological processes, and health outcomes are also discussed.

PMID- 11523337
TI  - Targeting effective treatment of bacterial meningitis. 2.

PMID- 11523338
TI  - What makes the day an analysis of the content of physician assistants' practice.

PMID- 11523340
TI  - [Methotrexate-induced lung pathology in patients with rheumatoid arthritis].

PMID- 11523339
TI  - Monitoring the antiplatelet action of aspirin.

PMID- 11523341
TI  - [Tolerance to nitrates in clinical practice].

PMID- 11523342
TI  - [The role of systemic and regional immunological reactions in pathogenesis of
      periodic disease].

PMID- 11523343
TI  - [Prevalence of ischemic heart disease in subjects with risk factors].

PMID- 11523344
TI  - [Effects of clinical indices and anti-angina therapy on the quality of life in
      patients with stable angina pectoris].
AB  - AIM: To determine effects of basic clinical indices and various antianginal drugs
      on quality of life (QL) assessed with general and special questionnaire before
      and after selection of antianginal therapy in patients with stable angina
      pectoris. MATERIAL AND METHODS: The study enrolled 89 patients with stable angina
      (functional class II-IV). They were examined before and after decision on
      adequate therapy. QL was assessed with questionnaires Disease Impact Profile and
      Seatle Angina Questionnaire (SAQ). Factors essential for QL were determined with
      factor analysis and multiple regression methods. QL correlation with exercise
      tolerance was examined. RESULTS: SAQ has identified a positive correlation of
      some parts and total QL with exercise tolerance (p < 0.05). Treatment
      satisfaction correlated negatively with intensity of threshold load (p < 0.05).
      Factors affecting QL differed in patients with selected and non-selected therapy.
      QL was affected by anginal severity and complications, concomitant diseases with
      chest pain, harmful habits. Intake of non-selected drugs (beta-adrenoblockers,
      aspirin, ACE inhibitors, saluretics, benzodiazepins) may deteriorate QL.
      CONCLUSION: It is impossible to describe QL with clinical characteristics alone.
      This is an independent index which requires a special estimation.

PMID- 11523345
TI  - [The role of intracardiac hemodynamic parameters in prognosis of cardiac failure
      in myocardial infarction patients].
AB  - Two-dimensional echocardiography was used to study intracardiac hemodynamics (end
      systolic, end diastolic volumes and left atrial ejection fraction; end systolic,
      end diastolic volumes and left ventricular fraction; mean pressure in the
      pulmonary artery; myocardial mass of the left ventricle) in 49 patients 2, 10 and
      30 days after onset of macrofocal myocardial infarction (MI). It was found that
      patients with and without cardiac failure after one year of the diseases
      significantly differed by volume and function of the left ventricle and atrium
      registered since MI day 2. Probability of cardiac failure in the postinfarction
      period may be estimated since the disease day 2 by an increase in the end
      systolic and end-diastolic volumes and left ventricular ejection fraction. A
      restrictive type of left ventricular diastolic dysfunction is one of the early
      prognostic criteria of cardiac failure in postinfarction period.

PMID- 11523346
TI  - [Direct revascularization of the myocardium and left ventricular diastolic
      function in patients with ischemic heart diseases].
AB  - Echocardiography (echo-CG) and stress-doppler echo-CG were performed in 78
      patients with ischemic heart disease (IHD) before and 1 to 8 years after the
      operation of direct myocardial revascularization (DMR). Polyposition
      coronarography with shuntography was used as a reference method. After DMR,
      stress-doppler echo-CG showed in capable shunts (vs resting values) that in
      insignificant reduction of early filling maximal rate (73.6 +/- 4.2 cm/s and 68.8
      +/- 3.1 cm/s, respectively) the rate of late filling lowered significantly (64.7
      +/- 4.5 cm/s and 58.1 +/- 3.9 cm/s, respectively), time of early filling
      inhibition (0.24 +/- 0.02 s and 0.18 +/- 0.04 s, respectively) and time of
      isovolumic relaxation (104.2 +/- 1.5 ms and 100.1 +/- 1.2 ms, respectively). An
      opposite picture was observed in patients with occlusive shunts. Thus,
      improvement of left ventricular diastolic function in IHD patients after
      aortocoronary bypass operation occurred only in capable shunts. Time course
      changes in the readings of stress-doppler-echoCG can indirectly characterize
      shunt function after DMR.

PMID- 11523347
TI  - [Processes of left atrial remodeling in myocardial infarction survivors as shown
      by esophageal rheography].
AB  - To study the condition of the left atrium (LA) in patients with myocardial
      infarction (MI), 112 MI patients were compared to 24 healthy controls by the data
      obtained at ultrasonic investigation of the heart and esophageal rheography.
      73.2% of the patients early after MI showed dilated LA. There were also changes
      in the ascending part of the rheographic atrial wave at its registration from the
      esophagus. Its marked prolongation (> 40% of the duration of the whole LA
      systole) is associated with alterations in the myocardial wall tonicity. If the
      above value was less, the number of supraventricular extrasystoles significantly
      increased, episodes of cardiac fibrillation occurred. Changed tonicity of the LA
      wall was accompanied also with prominent prolongation of the electrophysiological
      parameters of transesophageal pacing characterizing pacemaker's function and
      atrioventricular conduction. This suggests involvement not only left but also
      right atrium. Conclusion is that LA tonicity in MI is damaged and can be studied
      with esophageal rheography.

PMID- 11523348
TI  - [Endocrine arterial hypertension in young women with hormone-dependent diseases
      of the reproductive system].

PMID- 11523349
TI  - [Intracardiac interrelations as a reflection of cardiac remodeling in obstructive
      pulmonary diseases].
AB  - Echocardiographic correlations between cardiac compartments were studied in 51
      patients with obstructive ventilation disorders due to pulmonary diseases. All
      the compartments were closely related depending on the severity of the bronchial
      obstruction. In aggravation of the latter, integration of the atria, right atrium
      and left ventricle, right and left ventricles of the heart increases. The
      integration also grows between structural-functional indices of the left
      ventricle. At initial stages of bronchial obstruction functional and hemodynamic
      performance of the left ventricle depends more on its size, while later more on
      the wall thickness. It is demonstrated that obstructive disorders of ventilation
      promote closer integration of cardiac compartments, mobilization of compensatory
      hemodynamic reactions. The left ventricle plays an essential role in realization
      of staged compensatory reactions of the heart. Remodeling of the heart in
      obstructive pulmonary diseases is reflected in altered intracardiac
      relationships.

PMID- 11523350
TI  - [Analysis of autopsy data on patients who died at home of pneumonia].
AB  - According to 2675 autopsy protocols on patients who died at home in 1995-1997,
      pneumonia occurred in 298 cases (61.0% of the primary and 39.0% of the secondary
      pneumonia). Primary pneumonia developed more frequently in males (85.2%), was
      bilateral (52.2%), macrofocal (45.2%), pyoserous (80.7%). Complications were seen
      in 27.5%, purulent ones occurred in 64.0% of patients. Secondary pneumonia was
      also more frequent in males (69.8%). It complicated cardiovascular diseases in
      69.0% of cases. Small-focal and serous secondary pneumonia accounted for 46.6 and
      44.8% of the total secondary pneumonia cases.

PMID- 11523351
TI  - [The role of immune disorders in the development of respiratory diseases in
      families].
AB  - Two-stage immunological examination was performed in 59 subjects aged 12-55 years
      from 27 families with respiratory pathology in three generations. Their proband
      had chronic bronchitis. Prognostic estimation of changes in the immune status was
      made with matrix statistic analysis. The findings show heterogenic
      characteristics of physiological systems of the examinees from families with
      chronic bronchitis and non-uniform metabolic processes leading to respiratory
      pathology and allergic diseases. Disorders in immunologic homeostasis in the
      descendants of the probands with chronic bronchitis, chief signs in pathogenesis
      of chronic bronchitis in three generations, essential immunological factors in
      allergic persons are outlined.

PMID- 11523352
TI  - [Clinico-immunological aspects of renal lesions in rheumatoid arthritis].
AB  - The aim of this study was to examine the incidence of different renal lesions in
      rheumatoid arthritis (RA) and to determine their relationships with the type of
      previous drug therapy and with the specific features of immune disorders. Ninety
      four patients, 84 (89.9%) females and 10 (10.6%) males) with RA whose mean age
      was 45.2 +/- 11.9 years and duration of the disease 7.5 +/- 6.5 years were
      examined. Most of them had degrees 2 and 3 PA (62.7 and 24.4%, respectively).
      Systemic manifestations were encountered in 60 (63.8%) patients. Eighty one
      patients took nonsteroidal antiinflammatory drugs (NSAID) continuously: 18
      patients for a year, 32 for 5 years, 14 for 6 to 10 years, and 17 for over 10
      years. All the patients underwent clinical, laboratory, and instrumental study of
      partial functions of the kidney. Immunological study involved solid-phase
      immunoassay of IgA and IgM rheumatoid factor, von Willebrand factor antigens
      (WF:Ag), C-reactive protein. The serum concentrations were measured by the
      Mancini method. Changes in urinalysis and/or signs of decreased glomerular and
      tubular functions were found in 69 (73.%) patients, 25 (26.6%) had arterial
      hypertension. Tubular dysfunctions were more common [31 (32.9%) patients]. Signs
      of early renal failure were detected in 20 (21.2%) patients. There were no cases
      of acute renal failure. Amyloidosis, glomerulonephritis, pyelonephritis were
      diagnosed in 5 (5.3%), 16 (17%), and 13 (13.8%) patients, respectively. The above
      renal lesions were concurrent in some patients. Renal lesion correlated with the
      progression and severity of RA, the presence of systemic manifestations, and age.
      There was no relationship of both 5- and 10-year use of NSAID to the symptoms of
      renal disease. The use of these drugs for over 10 years was concurrent with the
      signs of chronic renal failure and arterial hypertension. Analyzing immunological
      disorders showed an association of increased erythrocytic sedimentation rates and
      WF:Ag with amyloidosis, that of higher IgA concentrations with proteinuria and
      tubular dysfunctions. It is concluded that renal lesion is common in RA, there is
      a predominance of tubular interstitial changes. In rare cases nephropathy is
      characterized by a benign course and fails to result in uremia. The symptoms of
      renal diseases are largely associated with RA progression and severity and the
      patients' age. Prolonged continuous use of NSAID may contribute to the
      development of renal failure. Different immune mechanisms are involved in the
      pathogenesis of glomerular and tubular nephropathy in RA.

PMID- 11523353
TI  - [Features of ultrasound imaging of chronic pancreatitis in combination with
      duodenal ulcer].
AB  - Analysis of ultrasonic scanning images demonstrated that each form of chronic
      pancreatitis (CP) has its characteristic US features. For example, if CP runs in
      the presence of duodenal ulcer, the pancreas presents with blurred outline, high
      parenchymal echogenicity, diffuse structural heterogeneity, short-term
      visualization of the Wirsung's duct. There were also gastric hypersecretion and
      signs of fibrosing ductulitis. Biliary and alcoholic CP is characterized by the
      absence of dynamic changes of the Wirsung's duct diameter.

PMID- 11523354
TI  - [Hemostasis in patients with duodenal ulcer, Helicobacter pylori infection and
      positive chronic gastritis].

PMID- 11523355
TI  - [The use of replacement hormonal therapy in menopausal women for the correction
      of antithrombogenic activity of the vascular wall].

PMID- 11523356
TI  - [A case of diagnosis of familial Albright's disease].

PMID- 11523357
TI  - [Profuse intravesical hemorrhage caused by Rendu-Osler-Weber disease].

PMID- 11523358
TI  - [Current views on terminology and classification of neurocirculatory asthenia in
      children and adolescents].

PMID- 11523359
TI  - [Results of experimental and clinical trials of moxonidine presented at the 8th
      10th European Hypertension Conferences].

PMID- 11523360
TI  - [Spinal lesions in generalized and multiple organ forms of tuberculosis].
AB  - The paper presents the results of examination of 152 patients with generalized
      and multiorgan lesions, mainly involving the vertebral column. The tuberculous
      process is defined in 64.4% of the patients as a generalized one by virtually
      simultaneously involving several organs and primarily the spine and respiratory
      organs and in 35.6% as a multiorgan one when symptoms of tuberculous spondylitis
      or tuberculosis of other organs rather than the lung appear some period (3 years
      or more) after organ involvement. Recommendations are given for pre- and
      postoperative treatment. All the patients with a preserved pathological process
      in the lung underwent operations on the spine in early periods (1-3 months) after
      admission to hospital.

PMID- 11523361
TI  - [Magnetic resonance imaging in the diagnosis of tuberculous arthritis].
AB  - A complex of clinical radiation and MRI studies of the joint was conducted in 45
      patients with tuberculous arthritis. Two major forms of tuberculous lesion of the
      joint were identified: primary osseous tuberculous arthritis (79.6%) and
      tuberculous allergic synovitis (20.4%). In patients with tuberculous allergic
      synovitis, MRI revealed a nonspecific exudative proliferative response of the
      synovial membrane and edema of the bone marrow and periarticular tissues. In
      primary osseous tuberculous arthritis, MRI showed tuberculous inflammation foci
      in the epiphysis of the bone; proliferative changes in the synovial membrane,
      destruction of cartilaginous, fibrous, and osseous structures, as well as
      periarticular abscesses.

PMID- 11523362
TI  - [Ultrasound diagnosis of retroperitoneal abscesses in spinal tuberculosis].
AB  - Sixty four patients were examined to elucidate the capacities and accuracy of
      ultrasonography (USG) in the diagnosis of retroperitoneal abscesses by ultrasound
      and X-ray studies. They were all operated on. Retroperitoneal abscesses were
      detected in patients (58 observations). X-ray retroperitoneal abscesses aroused
      doubts in 23% of cases. Ultrasonographic evidence was erroneous in 4.9% of cases.
      USG may reveal accumulation or absence of liquid pus, define the extent and
      number of chambers of retroperitoneal abscesses, which is helpful in answering
      questions as what surgical access should be chosen and what scope of a surgical
      intervention made. The safety and cost-effectiveness of the procedure allows a
      follow-up to be made.

PMID- 11523363
TI  - [Lymphotropic therapy with antitubercular agents in the treatment of tuberculous
      epididymitis].
AB  - Whether endolymphatic intranodular injection (ELII) of isoniazid can be used in
      the combined treatment of male genital tuberculosis is considered. Clinical
      trials were performed and this method used in the combined treatment of
      tuberculous epididymitis was assessed. The bacteriostatic activity and blood and
      tissue concentration of the agent given as ELII were studied and compared with
      its intramuscular route of administration. The authors show it possible to employ
      scrotum ultrasound studies to evaluate the efficiency of treatment and estimate
      the scope of a surgical intervention. Based on the data of morphological study of
      postoperative specimens, the authors defined the time and worked out criteria for
      epididymectomy in tuberculous epididymitis.

PMID- 11523364
TI  - [Gastric tuberculosis in the past and present].
AB  - The paper presents a historical review of the literature on the rare form of
      extrapulmonary tuberculosis--gastric tuberculosis. It is more frequently
      associated with tuberculosis of other organs and observes as an isolated form.
      The disease has no specific clinical signs. It is diagnosed as gastric carcinoma
      or ulcer by X-ray and in most cases endoscopic studies. The diagnosis of gastric
      tuberculosis can be made only by histological study of the resected stomach or
      its biopsy specimen. Antibiotic treatment for tuberculosis yields a good effect.

PMID- 11523365
TI  - [Criteria for clinical recovery in ocular tuberculosis].
AB  - The paper analyzes the results of examination of 314 patients with ocular
      tuberculosis, 120 of them had quiescent tuberculosis. Thirty one patients
      underwent tuberculin tests; 122 had fluorescence angiography and photo stress
      test; 120, lacrimal crystallography. To determine the degree of recovery requires
      a complex of criteria: neither clinical signs of active tuberculous inflammation
      in the retina and medium of the eye, no clinical, X-ray, and laboratory
      manifestations of tuberculosis of other sites, or a focal and much significant
      overall response to tuberculin in doses of 2 TE and 50 TE. If there are
      contraindications to tuberculin tests, a conclusion on recovery should be made by
      using fluorescence angiography of the fundus of the eye, crystallography of the
      tear and/or photo stress test in combination with blood biochemical and
      immunological studies.

PMID- 11523366
TI  - [Diagnosis and treatment of patients with tuberculous spondylitis].
AB  - The case histories of 452 patients with tuberculous spondylitis whose age ranged
      from 20 to 78 years are analyzed. The site of the process is given by the
      portions of the spine. Different events occurring in 40.4% of the patients are
      outlined. A correct diagnosis was established only in 24.1% of the patients in
      the first 3 months of the onset of a disease. It required a longer time in the
      remaining patients and this amounted to over 12 months in 13.5%. In the
      preoperative period, all the patients received chemotherapy in terms of the
      sensitivity of a causative agent. Surgical treatment involved resection of a
      vertebral lesion area and replacement of vertebral bodies with an autograft or an
      implant. Chemotherapy was continued in the postoperative period.

PMID- 11523367
TI  - [Chemotherapy regimens in osteoarticular tuberculosis in children during surgical
      treatment stages].
AB  - The outcomes of treatment in 280 children with tuberculosis of bones and joints
      are analyzed. A general chemotherapy scheme for tuberculosis makes treatment
      regimens recommend for use in different forms of osteoarticular tuberculosis,
      which have been differentiated by the site and rate of an osseous and
      intrathoracic process and by the magnitude of their complications. The regimens
      differed in dosages, routes, and duration of administration of antituberculous
      drugs.

PMID- 11523368
TI  - [Experience in standardization of immunological diagnosis of extrapulmonary
      tuberculosis].
AB  - An uniform multi-levelled approach to immunodiagnosis of tuberculosis of
      different sites is proposed with regard to latest information on the local immune
      response based on the detection of tuberculosis antibodies in blood and
      biological fluids from anatomic lesion areas. If necessary, immunological
      diagnosis is specified by using a set of serological tests and Koch's provocative
      test, as well as data on specific T-lymphocyte proliferation.

PMID- 11523369
TI  - [Detection of urinary Mycobacterium antigens by latex agglutination test].
AB  - A simple procedure was developed to defect infection with Mycobacterium
      tuberculosis by detecting its antigens in the urine. Prolonged higher urinary
      antigen titers after tuberculin are suggestive of its great effect on the child.
      The fact that Mycobacterium antigen titers are equal in BCG-vaccinated children
      with positive and negative Mantoux tests proposes to change the approach to
      substantiating revaccinations.

PMID- 11523370
TI  - [Identification of L-forms of Mycobacterium tuberculosis complex by polymerase
      chain reaction (PCR)].
AB  - Polymerase chain reaction (PCR) was used to verify the tuberculous origin of L
      forms isolated from clinical non-respiratory samples from patients with
      extrapulmonary tuberculosis. PCR was made by using cultured L-forms obtained from
      negative and positive cultures. PCR used a total of 60 cultured L-forms different
      in the morphology of colonies and the rate of growth. The total count of L-forms
      yielding positive amplification with M. tuberculosis complex-specific primers was
      51 (85%). L-form passages were subjected to PCR analysis. A total of 14 third
      generation L-forms were examined. They turned out to be positive. Thus, the fact
      that L-forms isolated from nonrespiratory clinical samples from patients with
      tuberculosis are most commonly L-forms of M. tuberculosis was genetically
      substantiated.

PMID- 11523371
TI  - [Extrapulmonary tuberculosis].

PMID- 11523372
TI  - [Value of molecular biological methods in the diagnosis of urogenital
      tuberculosis].
AB  - Enzyme immunoassay (EIA) was used to study the diagnostic value of determination
      of serum Mycobacterium tuberculosis (MBT) antibodies in 41 patients with active
      urinary tract tuberculosis, 14 with inactive tuberculosis and 140 with
      nontuberculous diseases of the urinary system. The sensitivity of EIA was 73%
      with 88.6% sensitivity. Polymerase chain reaction revealed the causative agent of
      tuberculosis in the urine samples of 16 out of 17 patients with active urinary
      tract tuberculosis, negative tests were observed in 4 cured patients and 39
      patients with nontuberculous diseases of the urinary tract (100% specificity).

PMID- 11523373
TI  - [Spectrum of tuberculosis antibodies in patients with tuberculosis and borderline
      urinary tract diseases].
AB  - The spectrum of tuberculosis antibodies detectable by indirect hemagglutination
      test, complement consumption, passive hemaagglutilution test (PHAT), and enzyme
      linked immunosorbent assay (EISA) in patients with urinary tract diseases
      (tuberculosis, nonspecific disorders) was studied. In untreated bacteria
      isolating patients in the early phase of disease, antibodies were found in 61.8%,
      their different types were detectable at different rates so it is more advisable
      to explore responses by using several serological tests. During treatment there
      is an increase in antibody detection rates by ELISA. At this time only can PHAT
      and ELISA be made. High seropositive rates (85-100%) are ensured by PHAT and
      ELISA in new case in end-stage disease. The antibodies are detected in 75 of the
      pretreated patients with nephrotuberculosis largely by PHAT and ELISA.
      Examination of patients with nonspecific disease by ELISA clarifies the clinical
      status of these patients.

PMID- 11523374
TI  - [Case of histiocytosis X mistaken for generalized tuberculosis].

PMID- 11523375
TI  - [Patients with pneumoconiosis and the tuberculosis-pulmonary services].

PMID- 11523376
TI  - [Classification of neurological disorders in tuberculous spondylitis].
AB  - The paper summarizes surveys of over 2500 patients with tuberculous spondylitis
      complicated by neurological disorders of the spinal cord. The authors identified
      5 grades of these disorders: from reflex disorders to limb plegia and pelvic
      dysfunctions. The classification proposed made it possible to clearly systematize
      spinal cord disorders in patients with tuberculous spondylitis, to establish a
      topical diagnosis and the severity of spinal cord lesions, to choose surgical
      accesses and method for stabilizing the spine, and to make a research processing
      of clinical and neurological data.

PMID- 11523377
TI  - [Radionuclide methods in the evaluation of renal lesions in different forms and
      localizations of tuberculosis (literature review)].

PMID- 11523378
TI  - [State and prospects of the development of the surgery of bones, joints and spine
      in adults (history of the development of surgical tuberculosis)].

PMID- 11523379
TI  - [St. Petersburg Research Institute of Phthisio-pulmonology and the guidelines for
      practical health care (information analysis)].

PMID- 11523380
TI  - [Extrapulmonary tuberculosis in children in Russia (epidemiology, clinical forms
      and their study)].
AB  - The paper provides the data of comprehensive epidemiological and clinical studies
      made at the Clinic of Tuberculosis in Children and Adolescents. Research
      Institute of Phthisiopulmonology, I. M. Sechenov Moscow Medical Academy, Ministry
      of Health of the Russian Federation, in the past 15 years and dedicated to
      extrapulmonary tuberculosis in children and adolescents with tuberculosis. Due to
      the specific features of manifestations of extrapulmonary tuberculosis in
      childhood and adolescence and to the existing system of prevention and early
      detection of the disease in children and teenagers in the Russian Federation, the
      number of children with severe generalized extrapulmonary tuberculosis is not on
      the rise despite that the epidemiological situation has aggravated in the past 15
      years. The clinical features of most common forms of extrapulmonary tuberculosis
      are shown and measures for their monitoring proposed.

PMID- 11523381
TI  - [Clinical and radiographic manifestations of tuberculous spondylitis in adults].
AB  - Data on 348 adult patients with tuberculous spondylitis treated in 1994-1999 are
      analyzed. The radiation manifestations of spondylitis first occurring in
      maturity, which amount to 82.3% in the clinical setting were studied in 112
      patients. In 50% of cases, spondylitis was a manifestation of multiorgan
      tuberculosis. The proportion of those with onset in youth increased (27.9).
      Isolated lesions of the corpus vertebrae were more frequently detected. The
      processes involving 2 vertebrae were predominant (61.2%), but complicated by foci
      at new levels. There was a drastic increase in the proportion of disseminated and
      multi-levelled spondylitis involving 3-9 vertebrae (36.9%). The exudative
      component of the inflammation was much pronounced, abscesses were extensive in
      all forms of spondylitis. Spinal cord deficit was noted in 68% of cases of
      thoracic and cervical spondylitis. MRI should be used for early diagnosis and
      determination of the extent of a process.

PMID- 11523382
TI  - Is there a "best" way to detect and minimize publication bias? An empirical
      evaluation.
AB  - Using 14 meta-analyses that included both published (n = 199) and unpublished (n
      = 50) randomized trials, we evaluated the utility of different analytical
      approaches to detect, assess robustness, and minimize publication bias in meta
      analysis. The rank correlation and graphical tests indicated funnel plot
      asymmetry in 3 and 7 of the 14 meta-analyses, respectively. The file drawer
      number estimates using Iyengar-Greenhouse method were between 1.5 and 4.7 times
      smaller compared to Rosenthal's estimates. The median difference between the Trim
      and Fill estimates and the actual number of missing studies was 1 (range -4, 6).
      Weighted estimation methods adjusted for publication bias and provided estimates
      of intervention effect close to the reference standard, on average. We showed
      there are differences in the conclusions one would reach clinically based on the
      different analytical approaches dealing with publication bias. Our results also
      suggest that the appropriate use of these methods improves the reliability and
      accuracy of meta-analysis.

PMID- 11523383
TI  - Methods for exploring heterogeneity in meta-analysis.
AB  - In meta-analysis, when the difference in results between studies is greater than
      would be expected by chance, one needs to investigate whether the observed
      variation in results across studies is associated with clinical and/or
      methodological differences between studies. This article reviews methods used in
      meta-analysis for exploring heterogeneity, including statistical tests for
      homogeneity, methods for visually displaying results of primary studies, methods
      for reducing heterogeneity, methods for investigating sources of heterogeneity,
      and identification of moderator variables or effect modifiers. The investigation
      of sources of heterogeneity in meta-analysis is by nature exploratory, and
      therefore its results should always be interpreted with caution. However, careful
      investigation of heterogeneity may provide an important second level of evidence
      that can be useful in suggesting direction of future research. Sometimes, it may
      provide clinically important results by indicating who might benefit more or less
      from a treatment or how an intervention should be applied.

PMID- 11523384
TI  - The use of numbers needed to treat derived from systematic reviews and meta
      analysis. Caveats and pitfalls.
AB  - Numbers needed to treat (NNTs) may be used to present the effects of treatment
      and are the reciprocal of the absolute difference between treatment and control
      groups in a randomized controlled trial. NNTs are sensitive to factors that
      change the baseline risk of trial participants: the outcome considered;
      characteristics of patients; secular trends in incidence and case-fatality; and
      clinical setting. NNTs derived from pooled absolute risk differences in meta
      analyses are commonly presented and easily calculated by meta-analytic software
      but may be seriously misleading because of heterogeneity between trials included
      in meta-analyses. Meaningful NNTs are obtained by applying the pooled relative
      risk reductions calculated from meta-analyses or individual trials to the
      baseline risk relevant to specific patient groups. This process will give a range
      of NNTs depending on whether patients are at high, low, or intermediate levels of
      risk, rather than a potentially misleading single number.

PMID- 11523385
TI  - Using Bayesian inference to perform meta-analysis.
AB  - Bayesian modeling offers an elegant approach to meta-analysis that efficiently
      incorporates all sources of variability and relevant quantifiable external
      information. It provides a more informative summary of the likely value of
      parameters after observing the data than do non-Bayesian approaches. This leads
      to direct probabilistic inference about model parameters such as the average
      treatment effect, the between-study variance, and individual study treatment
      effects. The latter are weighted averages of the common mean and individual study
      means with weights reflecting the amount of information provided by each study
      relative to the others. Homogeneity among these posterior study estimates
      indicates that pooling these studies is appropriate; heterogeneity suggests that
      some cause of between-study variation should be explored. The author describes
      the construction of such models and shows how to use them to estimate a common
      mean and regression slopes. Two examples illustrate the additional inferences
      available with the Bayesian methodology.

PMID- 11523386
TI  - Examining theoretical models through research synthesis. The benefits of model
      driven meta-analysis.
AB  - Quantitative research synthesis methods can be used to examine theoretical models
      for substantive research questions. Model-driven syntheses can address more
      complex questions than have typically been addressed in quantitative reviews in a
      more systematic and organized manner than in a traditional narrative review. A
      rationale and set of objectives for syntheses involving models are reviewed. The
      author describes how to incorporate models into each stage of a review, outlining
      problems and limitations that may arise at each stage. Examples from several
      model-driven syntheses illustrate the points made in the article.

PMID- 11523387
TI  - Simple pooling versus combining in meta-analysis.
AB  - The simple pooling of data is often used to provide an overall summary of
      subgroup data or data from a number of related studies. In simple pooling, data
      are combined without being weighted. Therefore, the analysis is performed as if
      the data were derived from a single sample. This kind of analysis ignores
      characteristics of the subgroups or individual studies being pooled and can yield
      spurious or counterintuitive results. In meta-analysis, data from subgroups or
      individual studies are weighted first, then combined, thereby avoiding some of
      the problems of simple pooling. The purpose of this article is to describe how
      simple pooling differs from meta-analysis, provide a detailed analysis of why
      simple pooling can be a poor procedure, and show that combining by meta-analytic
      methods avoids such problems.

PMID- 11523388
TI  - [Clinical and pathogenetic features of CNS damage in children with diphtheria].
AB  - The paper presents clinical and neurological features of diphtheritic
      polyneuropathy in 110 patients aged from 6 months to 14 years. The pattern of
      neurological complications appeared to be quite different for nontoxic and toxic
      forms; electroneuromyographical criteria of preclinical diagnosis of nervous
      disorders were determined. The role of a vascular factor in demyelinating
      process' genesis, immunohomeostasis implications in severity and outcomes of
      diphtheritic polyneuropathies, prognostic factors of the unfavorable course of
      the disease were defined. Scientifically grounded differential approaches to
      therapy were presented including application of vasoactive neurometabolites
      optimizing the processes of sanogenesis.

PMID- 11523389
TI  - [Speech and motor disorders in Rett syndrome].
AB  - Rett syndrome (RS) is a severe genetically conditioned disorder of an early
      childhood with an definite clinical phenotype in girls. Motor and speech
      disturbances are noted as the essential part of RS clinical picture. The
      variability of motor dysfunction and degree of speech deterioration were noted at
      different stages of the illness. The aim of the present investigation was to
      study dynamics of both speech and motor disturbances during 2-5 years of the
      course of the illness and to analyze a correlation of motor and speech functions'
      disorders. The study was performed in 50 girls with classical RS aged from 12
      months to 14 years. The data obtained show a gradual involvement of different
      brain cortex structures in pathological process during the course of RS
      (especially of frontal and temporal-parietal regions) at the early stage of the
      illness and subsequent spread of the pathological process with successive
      involvement of subcortical structures, cerebellum, brain stem and eventually
      spinal cord. The neurophysiological investigation showed a strong correlation of
      speech and motor disturbances' degree with the EEG parameters. The level of theta
      activity was significantly lower and the level of alpha- and beta-activity was
      significantly higher in EEGs of RS patients with more preserved speech and motor
      functions. In discussion mechanisms of motor and speech disturbances in RS were
      considered.

PMID- 11523390
TI  - [Acute attack-like endogenic psychoses in adolescents].
AB  - A clinical cohort was formed of 80 patients. The main criteria for including
      patients into the cohort were both the age of 12-17 years by the moment of the
      psychosis manifestation and a course of the disease in form of the attacks. On
      the basis of the study of psychopathological structure of the attacks from their
      onset to the remission and the follow-up study (5-10 years from the first attack)
      the following types of the psychotic episodes were determined: affective-oneiroid
      (19 patients); catatonic-oneiroid (11 cases); affective-paranoid (25) and
      paranoid (25). According to the modern classification, attack-like progredient
      catatonic and paranoid schizophrenia (36 patients) and schizoaffective psychosis
      (44 individuals) were diagnosed. A differential approach to therapy and
      rehabilitation has been grounded for separate groups of the patients.

PMID- 11523391
TI  - [Individual profile of functional asymmetries in children with cerebral palsy in
      application of medical-training suit].

PMID- 11523392
TI  - [An experience of the application of rispolept in childhood schizophrenia].
AB  - The efficiency of rispolept was examined in open non-comparative study which
      included 32 patients 6.5-16 years of age with schizophrenic spectrum disorders.
      Efficiency of the drug was estimated by clinical psychopathologic method together
      with the evaluation according to the PANSS. 5 patients were additionally
      estimated according to the Children's Yale-Brown Obsessive Compulsive Scale (CY
      BOCS) for the obsessive-compulsive disorders (a children version). The drug was
      used during 6 weeks in therapeutic doses from 4 to 8 mg/day. Reduction of the
      symptoms was 42% according to the PANNS for the positive items and 39% for the
      negative ones. There was also a significant decrease of manifestations of the
      obsessive-compulsive symptomatology according to CY-BOCS and of the depressive
      symptomatology according to the PANSS. Side effects comprised by vasotonic
      reactions (2 cases), oculomotor (2 cases) and torsion (one case) dyskinesias,
      which quickly disappeared after the correctors' administration. Extrapyramidal
      disorders were observed only after the increase of the dose up to 6-8 mg/day (3
      cases). Results of the study have shown a high therapeutic efficiency of
      rispolept for childhood schizophrenia.

PMID- 11523393
TI  - [Contingent negative variations in headache in children].
AB  - The paper presents a study concerning contingent negative variation (CND) in
      period between the attacks in 29 children with migraine, in 26 cases with a
      headache of tension (HAT) and in 16 healthy children. The age of the children
      examined was 7-14 years. The role of the age factor was shown in dynamics of the
      behavioral and electrophysiological CND parameters. Differences of
      electrophysiological CND parameters in children with migraine, in children with
      HAT and in healthy children of the same age are discussed as well as the results
      of the complex clinical-neurophysiological estimation of the efficiency of the
      prophylactic therapy in groups. CND method was considered to be quite perspective
      for differential diagnosis of primary headache in children.

PMID- 11523394
TI  - [Actual problems of modern perinatal neurology].

PMID- 11523395
TI  - [Antigens of histocompatibility in children with myasthenia gravis].
AB  - HLA-phenotype was determined in 59 juvenile patients of Russian nationality and
      in their 50 relatives by means of lymphocytotoxic test. There was a positive
      association with HLA-A1, B8 and DR3 and the negative one--with HLA-A2, A9, B5,
      B7, and DR7. The frequencies of HLA-A1, B8, DR3 were higher in boys than in girls
      with myasthenia. There were no significant changes of HLA frequencies in ocular
      form of the disease in comparison with the healthy group. The frequencies of HLA
      B8 and DR3 were significantly higher in relatives of the patients with juvenile
      myasthenia than in control population.

PMID- 11523396
TI  - [Results of day polygraph study in children with spastic forms of cerebral
      palsy].
AB  - Integrative possibilities of non-specific brain systems of 30 patients with
      cerebral palsy (CP) aged 6-10 years were studied in the process of day polygraph
      examination including the record of EEG, skin-galvanic reflex and ECG both at
      physiological rest and at functional trials. 14 children had spastic diplegia, 8
      children--hemiparetic form on the right side and 8 patients--on the left. The
      results obtained have indicated a systemic disneuroontogenesis of the middle
      structures mainly with the intrasystemic, intersystemic and interhemispheric
      manifestations of disintegration. It is concluded that regulatory conditions were
      created for forming a stable pathologic system maintaining disneuroontogenesis
      for strengthening of epileptic seizures during afferent stimulation and for
      considerable reduction of functional adaptation. That affects the compensatory
      abilities of the brain in patients with CP.

PMID- 11523397
TI  - [Prevalence and structure of borderline mental disorders in adolescent groups].
AB  - 328 schoolchildren and students of 13-17 years of age were examined by clinical
      epidemiological method. Point prevalence of borderline mental disorders and of
      their separate clinical forms were compared in two groups: pupils of secondary
      schools (148 cases) and students of the professional technical schools (PTS) (180
      individuals). General prevalence of the borderline mental disorders was equal to
      58.2%. It was higher in the group of pupils of secondary schools (66.7%) as
      compared with PTS students (49.3%). Neurotic disorders were more frequently found
      in pupils, while pathology of the personality--in PTS students. As the adolescent
      were of the same age and were under the influence of the same biologic factors
      (puberty period), the conclusion is made that the main factors in the formation
      of these differences were related to the social and cultural conditions.

PMID- 11523398
TI  - [Transcranial micropolarization in restorative therapy of spastic forms of
      infantile cerebral palsy].

PMID- 11523399
TI  - [Preliminary results of biolan application in children with mental disorders].

PMID- 11523400
TI  - [Diagnosis and therapy of speech disorders in children with mental and
      neurological pathology].

PMID- 11523401
TI  - [Psychosomatic concepts and infantile cerebral paralysis].

PMID- 11523402
TI  - [Chronic posttraumatic headache in juveniles].
AB  - The paper presents a comparative analysis of biologic, social-culturological and
      psychological factors of the premorbid, peculiarities of personality as well as
      the conditions of getting a slight craniocerebral trauma (CCT) as well as the
      therapy in the acute period and a psychosocial situation during 1 year after the
      trauma in juveniles with chronic posttraumatic headache (PTH) (74 individuals)
      and without it (24 cases). As the main clinical variation of a chronic PTH was
      chronic PTH of tension, we studied comparative anamnestic data and peculiarities
      of personalities in 22 juveniles with a chronic headache of tension without PTH
      in the anamnesis. It was found common pathogenetic mechanisms of the development
      of both traumatic and non-traumatic cephalgias; the risk factors of PTH
      chronicity were identified, that was quite necessary for the elaboration of
      effective rehabilitation programs.

PMID- 11523403
TI  - [Combination of interferon-alpha and all-trans-retinoic acid as a treatment for
      maintaining remission in high-risk group patients with acute myeloid leukemia].
AB  - AIM: To evaluate the efficiency of combination of interferon-alpha (INF) and all
      trans-retinoic acid (ATRA) as a treatment for maintaining remission in high risk
      group patients with acute myeloid leukemia (AML). MATERIALS AND METHODS: Three
      day INF + ATRA course was administered every 3 months to 22 patients with AML
      from high risk group (impossibility of drug therapy during the first complete
      remission, resistant forms of AML, relapses, secondary AML, acute promyelocytic
      leukemia after attaining molecular remission). RESULTS: INF + ATRA during
      remission maintained a long first complete remission (median 18 months) in
      patients with primary AML after small-volume drug therapy, led to long first and
      second complete remissions (median 12 months) in patients with resistant AML, and
      induced and maintained molecular remissions in patients with acute promyelocytic
      leukemia.

PMID- 11523404
TI  - [Functional activity and expression of P-glycoprotein in chronic myeloid
      leukemia].
AB  - AIM: To evaluate the prognostic significance of P-glycoprotein (Pgp) in chronic
      myeloid leukemia (CML). MATERIALS AND METHODS: Functional activity (rhodamine 123
      test) and expression of Pgp (binding of UIC2 monoclonal antibodies by cells) were
      evaluated by flow cytofluorometry. A total of 141 samples of peripheral blood
      from 121 patients with various stages of CML were examined. RESULTS: The number
      of patients whose cells express functionally active Pgp increases during the
      blast crisis (BC) in comparison with the chronic phase (CP). Repeated testing of
      patients with BC and CP showed that Pgp-expressing cells can disappear from the
      peripheral blood of patients despite the treatment by Pgp preparations and
      substrates. However the number of cases with expression and functional activity
      of Pgp increases in the course of BC. Several patients in whom functionally
      active Pgp was not detected during diagnosis of BC had longer BC phase than
      patients with the active protein. CONCLUSION: These data suggest that active Pgp
      contributes to CML BC (presumably to patient's response to therapy) but this
      contribution is not decisive.

PMID- 11523405
TI  - [Study of the time course of mixed chimerism by fluorescent in situ hybridization
      in patients with chronic myeloid leukemia after allogenic transplantation of bone
      marrow].
AB  - AIM: To determine the type of chimerism in patients with chronic myeloid leukemia
      (CML) in various periods after allogenic transplantation of bone marrow (TBM) and
      its association with subsequent relapse. MATERIALS AND METHODS: Ten patients were
      examined after allogenic TBM, which was performed during the chronic phase of CML
      in 9 patients and during acceleration phase in 1. Two patients received therapy
      with donor lymphocytes during relapse after transplantation. Time course of
      chimerism and minimum residual illness was studied by standard cytogenetic
      methods, fluorescent in situ hybridization (FISH) with DNA probes to centromer
      sites of X and Y chromosomes and BCR and ABL genes. The studies were carried out
      30, 60, 90, 180 days, 9 months, 1 year, and then every 6 months after
      transplantation. RESULTS: Mixed chimerism was observed in all patients during 9
      months after TBM. The count of host cells was 0.1-5.8% in 8 patients; later the
      count of autologous cells was less than 1% in 5 patients, and in 3 patients
      complete donor chimerism was observed. Clinical hematological remission was
      stable in these patients. Relapses of leukemia with 40 and 83.1% host cells
      occurred in 2 patients 13 and 23 months after transplantation, respectively.
      Donor lymphocytes were transfused in order to induce the graft versus host
      effect, and in patient No. 2 restoration of donor hemopoiesis was attained.
      CONCLUSION: Highly sensitive FISH method with DNA probe to centromer sites of X
      and Y chromosomes detects early relapse of the disease and demonstrates the time
      course of donor hemopoiesis recovery after transfusion of donor lymphocytes. The
      data indicate that 9 months after transplantation molecular cytogenetic studies
      should be carried out more often (once a month), particularly in patients with
      poor prognosis, for earlier detection of the relapse and beginning of
      immunotherapy.

PMID- 11523406
TI  - [Induction of co-stimulatory molecules on the surface of blast cells in patients
      with acute myeloid leukemia].
AB  - AIM: To compare the capacity of ionophore for calcium ions and growth factors
      (granulocytic-macrophagal colony-stimulating factor, interleukin-4, tumor
      necrosis factor) to induce costimulatory molecules on the surface of blast cells
      from patients with acute myeloid leukemia (AML). MATERIALS AND METHODS: The study
      was carried out in 6 patients with primary and resistant AML using culturing and
      flow cytometry. RESULTS: Blast cells obtained from patients during diagnosis of
      AML and after drug therapy of resistant AML acquire the dendrite phenotype under
      the effects of growth factors and Ca ion ionophore. CONCLUSION: Calcium
      metabolism modulators can be used for creation of antileukemic vaccines.

PMID- 11523407
TI  - [Variants of clinical course of T-cell leukemia from large granular lymphocytes].

PMID- 11523408
TI  - [Changes in hemostasis system in patients with hereditary thrombophilia caused by
      mutation of blood coagulation factor V ( factor V Leiden)].
AB  - AIM: To study the incidence of mutation of Leyden's factor V in patients with
      venous thrombosis and the hemostatic system in carrier of this genetic defect.
      MATERIALS AND METHODS: A hundred and one patients aged 15-69 years who had venous
      thrombosis and 10 individuals with mutation of Leyden's factor V without
      manifestations in the history of thrombosis were examined. Factor V gene
      mutations and the thrombocyte and plasma links of hemostasis were determined by
      routine methods. RESULTS: The Leyden's factor V genotype Arg506-->Gln was
      detected in 17 of the 101 patients with venous thrombosis. Patients and
      asymptomatic individuals with this factor were found to have significant
      hypercoagulation, as evidenced by lower activated protein C-resistance index,
      higher factor VIII (von Willebrand's factor) activity, elevated von Willebrand's
      factor antigen levels, and enhanced intravascular platelet activation. In the
      presence of lupoid anticoagulant, hypercoagulation increased and protein C
      activity decreased. CONCLUSION: Detection of signs of hypercoagulation in
      patients with inherited thrombophilia at recovery in carriers of Leyden's factor
      V without clinical manifestations of thrombosis shows it necessary to make a
      particularly careful monitoring of the hemostatic system in these subjects. This
      is especially important for hypercoagulation-predisposing situations, such as
      pregnancy, surgical interventions, long-term immobilization, use of
      contraceptives, etc. when preventive measures may be used to prevent thrombotic
      events.

PMID- 11523409
TI  - [From the editorial board].

PMID- 11523410
TI  - [Apoptosis and proliferative activity of bone marrow cells in patients with
      aplastic syndromes as evidenced by trephine biopsy].
AB  - AIM: To clarify the effect of cyclosporin A (CSA) on the apoptosis and
      proliferative activity of bone marrow cells in patients with aplastic syndromes
      by trepanobiopsy evidence. MATERIALS AND METHODS: The TUNEL immunohistochemical
      assay was used to study apoptosis of bone marrow cells in the histological
      specimens from 24 patients: 8 with refractory anemia (RA), 8 with acute small
      proportion leukemias [RA with excessive blasts (RAEB) + RAEB in transformation
      (RAEBt)], 3 with acute non-lymphoblastic leukemia (ANLL), 5 with
      lymphogranulomatosis (LGM). Control apoptosis examination was made in 10 patients
      treated with CSA. The proliferative activity of bone marrow cell was evaluated by
      bone marrow histological specimens from 10 patients (8 patients with RA and 2
      with RAEB + RAEBt) at the onset of disease and during CSA therapy in the
      immunohistochemical test with primary nuclear antigen Ki-67 antigen antibodies.
      Changes in the proliferative activity and degree of apoptosis of bone marrow
      cells were assessed in relation to the cellularity detectable by the histological
      specimens. RESULTS: Patients with RA showed an increase in bone marrow cell
      apoptosis to 25.375 +/- 6.874 (-10.8 +/- 5.122 and 8.333 +/- 5.84 in controls and
      ANLL patients, respectively). The cells of hemopoiesis and stromal
      microenvironment are in the process of cell death. Higher bone marrow cellularity
      is observed in CSA-treated patients at clinical and hematological remission,
      which is followed by rises in the index of proliferation and the degree of
      apoptosis. CONCLUSION: The clinical effect of CSA in patients with aplastic
      syndromes is induced by its direct or mediated stimulating effect on pluripotent
      stem cells of hemopoiesis, by increasing bone marrow cellularity at the expense
      of clonal and/or normal hemopoiesis.

PMID- 11523411
TI  - [Effectiveness of cyclosporin A in the treatment of adult patients with aplastic
      anemia].
AB  - AIM: To evaluate the efficacy of cyclosporin A (CyA) at different stages of
      immunosuppressive therapy (IST) in patients with aplastic anemia (AA). MATERIALS
      AND METHODS: The efficacy of CyA was studied in 56 patients with AA. The agent
      was orally given in an initial dose of 10 mg/kg as solution or capsules. Its
      daily dose during a treatment course varies with the serum CyA levels and
      clinical tolerance. CyA was used in 17 patients at the first stage of treatment,
      in 8 with recurrent AA, and in 31 after ineffective previous therapy
      (antilymphocytic globulin therapy--ALGT, splenectomy). Erythropoiesis was
      evaluated by the count of erythrokaryocytes and by relative erythroid hyperplasia
      of the bone marrow and by using erythrokaryocytic PAS reaction, by calculating
      the total count of sideroblasts and ringed sideroblasts. RESULTS: A positive
      response was obtained in 41% of the patients with AA. Its pattern depended on the
      severity of AA, on CyA use regimens, and treatment duration: when treatment with
      CyA lasted 6-12 months, its efficacy considerably increased (positive responses
      in severe AA and mild AA being in 64 and 94%, respectively). It has been found
      that high (over 6%) baseline bone marrow ringed sideroblasts in patients with AA
      may be regarded as a poor predictor in the context of the efficacy of this agent.
      CONCLUSION: CyA is recommended for combined IST in patients with AA at the second
      stage of treatment (after antilymphocytic globulin administration) in order to
      perform long-term (12-month) immunosuppression by choosing the optimum dose on an
      individual basis and by continuously monitoring the quality of a response.

PMID- 11523413
TI  - [Preoperative embolization of the splenic artery in patients with blood system
      diseases].
AB  - AIM: To develop and introduce X-ray endovascular preocclusion of the splenic
      artery in general surgical patients with different forms of cytopenias as
      preparation for further surgical treatment. MATERIALS AND METHODS: Data on 12
      splenic arterial occlusions in patients with different diseases of the blood
      system. RESULTS: Despite the severity of the underlying process, the use of X-ray
      endovascular preocclusion of the splenic artery in patients with different
      hematological diseases made it possible to make the so-called bloodless
      splenectomy on short notice, then a required cavitary operation or in the
      immediate postembolization period if there were emergency indications or some
      time later if the patient's status allowed. CONCLUSION: When patients with blood
      system diseases attended by thrombocytopenia, anemia, leukopenia are indicated to
      have surgical treatment of some contaminant diseases, it is necessary to perform
      X-ray endovascular splenic arterial occlusion at the first stage, then make a
      major intervention when blood parameters have improved.

PMID- 11523412
TI  - [Treatment of acute lymphoblastic leukemia in adults as an unsolved problem].

PMID- 11523414
TI  - [Long-term effects of captopril treatment on the course of stable effort angina
      pectoris and structural-functional characteristics of platelets in patients with
      hypertension and ischemic heart disease].
AB  - AIM: To assess clinical efficacy and effect on platelet alterations of 12-month
      captopril monotherapy in essential hypertension (EH) patients with coronary heart
      disease (CHD). MATERIAL AND METHODS: A randomized placebo-controlled parallel
      study was performed. Arterial blood pressure (BP), frequency of angina pain
      attacks, standard submaximal bicycle exercise test (BET), echocardiography, ADP
      induced platelet aggregation (PA), levels of cholesterol (CH), lipid peroxidation
      products, intracellular Ca, Ca(++)-ATPase activity were studied before and 2
      weeks, 2, 6 and 12 months after captopril therapy in 68 males aged 35-58 years
      with moderate EH in combination with CHD, stable angina of effort and normal left
      ventricular ejection fraction (57.5 +/- 1.2%). RESULTS: In spite of a stable
      antihypertensive effect of C within all the treatment period, frequency of
      anginal pain attacks and number of positive BET markedly reduced only during 6
      months of C therapy. Left ventricular hypertrophy regression was not registered.
      Of all the platelet parameters only Ca(++)-ATPase, Ca and malonic dialdehyde
      (MDA) beneficial changes persisted for 12 month treatment period: Ca(++)-ATPase
      activity increased, Ca and MDA content reduced. The other platelet parameters
      were less persistent. BP lowering correlated with Ca(++)-ATPase, CH, MDA and PA
      changes whereas the number of anginal pain attack correlated with CH and PA
      reduction. CONCLUSION: A beneficial effect of captopril on BP persisted for 12
      months, on angina symptoms--for 6 months. One of the mechanisms of
      antihypertensive and antianginal effect of captopril is attributed to platelet
      alterations correction.

PMID- 11523415
TI  - [Constitutional pericentric inversions of chromosomes 5, 7 and 9 in patients with
      myeloid tumors].

PMID- 11523416
TI  - [Effective combined treatment of thymus carcinoma with complete eradication of
      tumor after neoadjuvant therapy in a patient with severe form of hemophilia A].

PMID- 11523417
TI  - [Combined radiation injuries: clinical syndromes, time course of skin burns,
      possible elements of pathogenesis].

PMID- 11523418
TI  - [Placental blood: alternative source of hemopoietic stem cells for
      transplantation. Creation of umbilical blood banks].

PMID- 11523419
TI  - [Experience in the use of losek (omeprazole) in gastroenterology].

PMID- 11523420
TI  - [History of creation and first years of activities of hospital clinics of the
      Medical Department of Moscow University].

PMID- 11523421
TI  - [Current strategies of pathogenetic therapy of Alzheimer's disease].
AB  - This is a review of the data available in the literature and the authors' own
      findings on pathogenetical rationale for the use and clinical study of current
      treatments for Alzheimer's disease (AD) (synonym: Alzheimer-type dementia). In
      the past decade many attempts have been made at targeting different links of the
      pathogenesis of a neurodegenerative process that underlie AD. Several areas of
      pathogenetical therapy for AD have been developed on the basis of experimental
      studies and pilot clinical tests. The most developed areas are as follows:
      various compensatory (replacement) treatments aimed at overcoming
      neurotransmitter deficit in different neuronal systems that are damaged in AD to
      a greater or lesser extent; neuroprotective therapy promoting increased viability
      (survival) of neurons and their plasticity, and vasoactive therapy. Rather new
      directions of AD pathogenetic therapy, such as antiinflammatory and hormonal
      therapy along with antiamyloid therapeutic strategies are still under study.

PMID- 11523422
TI  - [Pathogenesis and treatment of multiple sclerosis (state of the art in 2000)].
AB  - Multiple sclerosis is universally accepted to be a multifactorial disease whose
      pathogenesis is due to a complex of immunopathological and pathochemical
      reactions. The key assumption is that only early stages of immunopathological
      chain reactions involve specific recognition of antigens by autoreactive T cells
      and antibodies. These early events trigger a demyelinating process at whose later
      stages of importance are macrophages and glial cells, particularly those of
      microglia, which produce a great deal of biologically active substances and
      inflammatory mediators. A deeper insight into the pathogenesis of multiple
      sclerosis has provided new therapeutical approaches to treating this disease. In
      addition to that there are effective IFN-beta drugs (Betaferon, Rebif, Avonex)
      and Copaxone, other pathogenetically justified approaches are still under search.
      The next step of further studies is to identify subtypes of multiple sclerosis
      and to choose a therapy in accordance with its pathogenetical mechanisms.

PMID- 11523423
TI  - [Epilepsy: epidemiology and social aspects].

PMID- 11523424
TI  - [Molecular cytogenetic studies of chromosomal abnormalities and disorders in
      nervous and mental diseases: search for biological markers for diagnosis].
AB  - Molecular cytogenetic and cytogenetic studies of chromosomal disorders in
      patients with nervous and mental disorders were conducted using currently
      available approaches, including fluorescence in situ hybridization (FISH) with an
      original collection of centromeric, telomeric, region-specific DNA probes. A
      novel in situ hybridization protocol for rapid (15-30 min) chromosomal detection
      procedure and directly fluoresceinated DNA probes are recommended for use in
      mental retardation and congenital malformations. Chromosomal abnormalities could
      be detected in postnatal cases with chromosomal structural rearrangements,
      aneuplodies of gonosomes (including mosaicisms) and autosomes (including marker
      chromosomes). Molecular cytogenetics (or FISH diagnosis) can be used when
      classical cytogenetic methods are insufficient. The authors' experience shows
      that FISH should be utilized only as an adjunctive test for classical cytogenetic
      studies when banding techniques are ineffective; cytogenetic methods should be
      utilized for the preclinical diagnosis of Rett's syndrome. Detection by original
      probes gives an additional possibility in FISH analysis. Molecular cytogenetic
      methods are shown to provide a rapid accurate approach to studying and diagnosing
      chromosomal anomalies and disorders in mental retardation with congenital
      malformations and Rett's syndrome in children and to exploring aneuploidies in
      the postmortem cell samples from schizophrenic patients.

PMID- 11523425
TI  - [Progress in neurosciences: initiatives within the framework of the program
      "Brain Decade (1990-2000)"].
AB  - The paper describes basic scientific and practical results obtained in the past
      decade at the Research Institute of Neurology, Russian Academy of Medical
      Sciences, in the following areas: cerebrovascular diseases, degenerative and
      demyelinating diseases of the nervous system. Particular attention is paid to the
      development of national criteria for brain death, a concept of structural and
      functional levels of the vascular system, that of brain pathology in
      atherosclerosis and essential hypertension, rapid methods for evaluating neuronal
      apoptosis, a new method for diagnosing prionic diseases caused by a classical
      viruses, and a new method for histochemical diagnosis of the degree of reparative
      peripheral nerve processes in polyneuropathies and to the discovery of two new
      hereditary nervous system diseases, to direct DNA diagnosis of torsion dystonia,
      Wilson-Konovalov disease, Friedreich's disease, to the setting up of a national
      representative family register and DNA data bank for monogenous hereditary
      diseases, to the development of indications for craniocerebral bypass of cerebral
      vessels in multiple occlusions of great cerebral arteries and indications for
      programmable plasmapheresis in a number of autoimmune diseases of the nervous
      system, to the development of rehabilitative programmes for stabilogram
      biocontrol, markers of an active embologenous atherosclerotic plaque in the
      arteries supplying blood to the brain, etc.

PMID- 11523426
TI  - [Autoimmune mechanisms in the genesis of developmental abnormalities of the
      nervous system].
AB  - The level of autoantibodies to nerve growth factor (NGF) was measured in the sera
      of infants with mental dysontogenesis and of patients with different mental
      diseases. The findings suggest that the excessive levels of NGF autoantibodies
      are responsible for nervous malformations that underlie some nervous and mental
      diseases and that the body has a certain capacity to normalize clinical and
      immunochemical parameters. A particular pattern of manifestations of these
      disorders depends on some factors and primarily on genetic predisposition. NGF
      autoantibody levels are recommended to be estimated during screening of infants
      to form mental dysontogenesis risk groups.

PMID- 11523427
TI  - [Impaired cerebral glutamate metabolism in mental diseases (Alzheimer's disease,
      schizophrenia].
AB  - There is strong evidence for the involvement of the neurotransmitter glutamate
      system in the pathogenesis of Alzheimer's disease and schizophrenia. In these
      mental diseases, the brain shows changes in the levels of glutamate and in the
      function and expression of its transporters and receptors. Since the levels of
      glutamate are largely determined by the rate of its metabolism, the changes of
      its concentrations may be associated with dysfunctions of appropriate enzymes.
      Actually, disturbances of glutamate metabolic enzymes, such as glutaminase,
      glutamate decarboxylase, and glutamine synthetase were detected in the brain of
      patients with Alzheimer's disease. The alterations in the expression of glutamine
      synthetase, glutamine synthetase-like protein, and three isoenzymes of glutamate
      dehydrogenase in the frontal cortex of patients with schizophrenia suggest that
      there are impaired glutamate metabolism in this mental disease and Alzheimer's
      disease.

PMID- 11523428
TI  - [Levels and molecular heterogeneity of serotonin transporter protein in platelets
      of patients with different mental diseases: a comparative analysis with the use
      of monoclonal and polyclonal antibodies].
AB  - Polyclonal (PAb) and monoclonal (MAb) antibodies to CT2-epitope of the C-terminal
      fragment of serotonin transporter (SERT) protein were used to study the levels
      and molecular heterogeneity of platelet SERT in healthy donors and patients with
      affective (AD) and somatoform (SD) disorders, schizoaffective disorder (SAD) and
      schizophrenia. SERT was found to exist as high molecular wight (HMW) and low
      molecular weight (LMW) forms separated after electrophoresis. The levels of HMW
      and LMW forms of SERT were significantly, decreased in mentally ill patients as
      compared to healthy individuals. Unlike PAb, horse radish peroxidase (HRP)
      conjugated MAbs were more sensitive and specific to SERT and could detect the LMW
      form of SERT as a duplet protein form with MW about 40 and 43 kDa. The MAb to CT2
      C-terminal fragment of SERT conjugated with HRP is considered to be a new
      valuable tool for further investigation of SERT expression, properties, and
      posttranslation modification in the controls and in patients with different
      psychopathology.

PMID- 11523429
TI  - [Morphometric study of ultrastructural changes in oligodendroglial cells in the
      postmortem brain in endogenous psychoses].
AB  - A qualitative and quantitative electron microscopic study of oligodendroglial
      cells was performed in autoptic (4-6.5 hours after death) prefrontal area 10 in
      16 cases of schizophrenia, 6 cases of bipolar affective disorder and 16 normal
      controls, as well as in the caudate nucleus in same schizophrenic and control
      cases. The signs of reactive, regressive, and progressive changes of
      oligodendroglia were described in endogenous psychoses. ANOVA demonstrated a
      significant decrease in the area of the nucleus, in the volume density of
      euchromatin, in the volume density and count of mitochondria in oligodendroglial
      cells in the caudate nucleus and prefrontal area. In affective psychosis, there
      was a significant reduction in the area of the nucleus and in the volume density
      of euchromatin and slight changes in cellular organelles. No correlation between
      the changes and the postmortem interval, age, and neuroleptic therapy, as well as
      the most pronounced changes in oligodendroglial cells in subgroups of continuous
      schizophrenia and those with predominantly negative symptoms suggest the
      involvement of abnormal oligodendroglial cells in the pathogenesis of endogenous
      psychoses.

PMID- 11523430
TI  - [Quantitative EEG correlates of the human frontal lobe dysfunction].
AB  - Increased central-parietal EEG theta-2 activity (about 6.5 per sec) was found in
      children with cognitive disorders (in Rett's syndrome, fragile X-syndrome,
      infantile autism) and in elderly patients with Alzheimer-type dementia (with
      prevalence of neuropsychological "frontal" disorders) in the presence of
      suppressed alpha rhythm. This theta-activity was closely associated with
      cognitive deficits and possessed a specific functional topography, namely it
      focused in the parietal region and suppressed by both visual stimulation and
      motor tests. The similar EEG pattern was observed in some patients treated with
      neuroleptics and/or during hyperventilation. By taking into account the data
      available in the literature on motor, oculomotor, regional cerebral blood flow
      and the probability prediction in frontal lobar dysfunction, it is suggested that
      the theta-activity described appears in the visuomanual coordination system and
      is a physiological correlate of decreased functional status of frontal lobes.

PMID- 11523431
TI  - [Current approaches to the problem of autism in childhood].
AB  - The paper provides clinical and catamnestic descriptions of 240 children with
      infantile autism; 160 with atypical autism (of them 100 had schizophrenic
      attacks, 60 presented with mental retardation concurrent with atypical autism (in
      phenylketonuria, tuberose sclerosis, Down syndrome, Martin-Bell syndrome), 20
      with Asperger's syndrome, 60 with Rett's syndrome, 20 with psychogenic paraautism
      according the Nissen classification. The similarity of autism-like disorders and
      atypical autism was considered. Syndromal verifications in accordance with ICD-10
      (1994) and ICD-10 (1999) in Russian versions and clinical nosological
      verifications adopted in Russia were studied in all the examinees. New approaches
      to treating patients with autistic disorders were developed.

PMID- 11523432
TI  - Longitudinal changes in bone lead concentration: implications for modelling of
      human bone lead metabolism.
AB  - In this study, 539 occupationally exposed subjects received in vivo bone lead
      measurements using 109Cd excited K X-ray fluorescence (109Cd K XRF). Of these
      subjects, 327 had previously been measured five years earlier. Measurements were
      made from both tibia and calcaneus samples, taken to reflect cortical and
      trabecular bone, respectively. Changes in tibia lead concentration related
      negatively to initial tibia lead concentration and positively to both lead
      exposure between the measurement dates and initial calcaneus lead concentration.
      This finding confirmed and strengthened the interpretation of an earlier study
      involving fewer subjects. With the larger data set it was possible to examine
      subgroups of subjects. This showed that people aged less than 40 years had a
      shorter half-life for the release of lead from the tibia (4.9, 95% CI 3.6-7.8
      years) than did those older than 40 (13.8, 95% CI 9.7-23.8 years). Similarly,
      less intensely exposed subjects (lifetime average blood lead < or = 25 micrograms
      dL-1) had a shorter tibia lead half-life (6.2, 95% CI 4.7-9.0 years) than those
      with a lifetime average blood lead > 25 micrograms dL-1 (14.7, 95% CI 9.7-29.9
      years). Age and measures of lead exposure were strongly correlated; nevertheless,
      age matched subgroups with high and low intensity exposures showed clearance
      rates that were significantly different at the 10% level, with the lower exposure
      intensity again being associated with the faster clearance. These findings imply
      that current models of human lead metabolism should be examined with a view to
      adjusting them to account for kinetic rates varying with age and probably also
      with exposure level.

PMID- 11523433
TI  - Evaluation of the effect of data pre-treatment procedures on classical pattern
      recognition and principal components analysis: a case study for the geographical
      classification of tea.
AB  - A simple transformation that uses the half-range and central value has been used
      as a data pre-treatment procedure for principal component analysis (PCA) and
      pattern recognition techniques. The results obtained have been compared with the
      results from classical normalisation of data (mean normalisation, maximum
      normalisation and range normalisation), autoscaling and the minimum-maximum
      transformation. Three data sets were used in the study. The first was formed by
      determining 17 elements in 53 tea samples (901 pieces of data). The second and
      third data sets arose from two long-term drift studies performed to examine
      instrumental stability at standard and robust conditions. The instruments used
      were an inductively coupled plasma atomic emission spectrometer and an
      inductively coupled plasma mass spectrometer. Each drift diagnosis experiment
      consisted of replicate determinations of a test solution containing 15 analytes
      at 10 mg l-1 over 8 h without recalibration. Twenty-nine emission lines were
      determined 99 times, thus, each data set was formed by 2881 pieces of data. Data
      pre-treatment was applied to the three data sets prior to the use of principal
      component analysis, cluster analysis, linear discrimination analysis and soft
      independent modelling of class analogy. The study revealed that the half-range
      and central value transformation resulted in a better classification of the tea
      samples than that achieved using the classical normalisation. The loadings in the
      PCA for the long-term stability study, under both standard and robust conditions,
      were found to be similar to the drift trends only when the minimum-maximum
      transformation and the mean or maximum normalizations were used as data pre
      treatments.

PMID- 11523434
TI  - Bromine and iodine in 1997 UK total diet study samples.
AB  - Concentrations of bromine and iodine were analysed in samples from the 1997 UK
      Total Diet Study (TDS) using ICP-MS. The data has been used to estimate dietary
      exposures of UK consumers to these elements from the typical UK diet. Samples for
      the 20 TDS food groups were obtained from 20 towns in the UK in 1997 and analysed
      in 1998/99 for total bromine and total iodine concentrations. These samples were
      also analysed for 12 other elements. The UK regulatory authority had considered
      iodine recently, but had not considered bromine before. This survey provides up
      to-data baseline data for those two elements. Iodine concentrations are similar
      to those found in recent surveys. Levels of bromine were consistent with previous
      data where available. Dietary exposures to bromine and iodine were calculated to
      see if there were any risks to health from the levels of these elements found in
      the UK diet. The estimated population average exposure to iodine was 0.25 mg d-1,
      which is within the range of previous estimates (1995, 0.21 mg d-1; 1991, 0.17 mg
      d-1; 1985, 0.28 mg d-1). The estimated population average exposure to bromine was
      3.6 mg d-1.

PMID- 11523435
TI  - Brominated flame retardants in plasma samples from three different occupational
      groups in Norway.
AB  - Brominated flame retardants (BFRs) are widely used in plastics, textile coatings,
      electrical appliances and printed circuit boards to prohibit the development of
      fires. In order to investigate how exposure to BFRs is related to specific
      occupations, samples were obtained from Norwegian individuals working at an
      electronics dismantling facility, in the production of printed circuit boards, or
      as laboratory personnel. Nine BFRs were quantified in the plasma samples: 2,4,4'
      tribromodiphenyl ether (BDE-28), 2,2',4,4'-tetrabromodiphenyl ether (BDE-47),
      2,2',4,4',5-pentabromodiphenyl ether (BDE-99), 2,2',4,4',6-pentabromodiphenyl
      ether (BDE-100), 2,2',4,4',5,5'-hexabromodiphenyl ether (BDE-153), 2,2',4,4',5,6'
      hexabromodiphenyl ether (BDE-154), 2,2',3,4,4',5',6-heptabromodiphenyl ether (BDE
      183), 2,4,6-tribromophenol (TriBP) and tetrabromobisphenol A (TBBP-A). The BFRs
      were extracted from plasma using solid-phase extraction (SPE). The plasma lipids
      were decomposed by treatment with concentrated sulfuric acid directly on the SPE
      column, prior to the elution of the BFRs. Following diazomethane derivatization,
      the samples were analysed by gas chromatography-electron capture mass
      spectrometry. The subjects working at the electronics dismantling plant had
      significantly higher plasma levels of TBBP-A and BDE-153 compared to the other
      groups, and the heptabrominated congener BDE-183 was only detected in plasma from
      this group. TriBP was generally the most abundant BFR present, and the plasma
      concentrations were in the range 0.17-81 ng g-1 lipids. BDE-47 was the dominant
      BDE congener in all the individual samples and the levels were in the range 0.43
      14.6 ng g-1 lipids. The total amounts of the seven BDEs were 8.8, 3.9 and 3.0 ng
      g-1 lipids for the group of electronics dismantlers, circuit board producers and
      laboratory personnel, respectively. Generally, large variations in the individual
      concentration levels were found within the groups, especially in the group of
      electronics dismantlers, where the relative standard deviations for BDE
      concentrations were in the range 23-164%. The levels of BFRs were not correlated
      to age or the level of 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153). The present
      work indicates that the population in Norway is exposed to several BFRs, probably
      with food as a major source. The elevated level of higher brominated BDEs and
      TBBP-A in the plasma from the workers at the dismantling plant suggests an
      additional occupational exposure for these individuals. Thus, human exposure to
      BFRs seems to originate from a combination of different sources; however, further
      studies investigating plasma samples from a larger number of individuals are
      necessary for a more complete assessment of human exposure pathways to these
      environmental contaminants.

PMID- 11523436
TI  - Solvation descriptors for the polychloronaphthalenes: estimation of some
      physicochemical properties.
AB  - Solvation descriptors for the 75 polychloronaphthalenes have been derived from
      literature data on various properties. These descriptors (S, the
      dipolarity/polarizability; B, the hydrogen bond basicity; L, the logarithm of the
      gas-hexadecane partition coefficient; E, the excess molar refraction; V, the
      McGowan volume) have been used to estimate properties that may be environmentally
      relevant. Thus, for all 75 polychloronaphthalenes, we estimate values for the
      water-octanol partition coefficient, as log POCT, the aqueous solubility, as log
      S, the gas-water partition coefficient, as log KW, and the gas-dry octanol
      partition coefficient, as log KOCT. We further show that it is trivial to
      estimate other properties for all 75 polychloronaphthalenes; these properties
      include a number of gas-solvent and water-solvent partitions, air-plant and water
      plant partitions, and permeation of human skin from water.

PMID- 11523437
TI  - Chemical monitoring and evaluation of the water quality of the Douro River at the
      Crestuma-Lever dam.
AB  - Water taken from the Crestuma-Lever dam on the Douro River was evaluated
      considering the Portuguese Decree-law no. 236/98 of 1st August, 1998. This paper
      presents the metrological characteristics, validation of analytical methodologies
      and the data obtained from seasonal samplings. The test parameters selected are:
      temperature, pH, chloride, conductivity, carbon dioxide, alkalinity, hardness,
      oxidability, dissolved oxygen, BOD5, total suspended solids, sulfide, phosphate,
      silica, ammonium, nitrite, nitrate, sulfate, sodium, potassium, calcium,
      magnesium, iron, manganese, copper and zinc. From data analysis we can conclude
      that the water presented the following characteristics: a pH situated in the
      neutral zone; a median mineralization; a medium hardness; well oxygenated water;
      and a carbonate hardness exclusively due to bicarbonates. The temperature, pH,
      dissolved oxygen, ammonia, chlorides, sulfates, copper, zinc and BOD5 were
      compared with the legal limits presented in annexes XXI and I of Decree-law
      236/98. The results relating to total hardness, nitrites, calcium, magnesium,
      sodium, potassium, aluminium, sulfides and oxidability were compared with the
      legal values in annex VI as there are no limits relating to these parameters in
      annexes XXI and I.

PMID- 11523438
TI  - Organic contaminants and trace metals in flounder liver and sediment from the
      Amsterdam and Rotterdam harbours and off the Dutch coast.
AB  - Organic contaminants [polychlorinated biphenyls (PCBs), organochlorine pesticides
      (OCPs), polybrominated diphenylethers (PBDEs), nonylphenols], organotin compounds
      and trace metals (cadmium, chromium, mercury and zinc) were determined in
      flounder (Platichthys flesus) liver and sediment from the Amsterdam harbour
      (North Sea Canal) and Rotterdam harbour (Euromonding) and off the Dutch coast
      between the Amsterdam and Rotterdam harbour mouths in order to assess the level
      of contamination in these harbours and to study contamination gradients.

PMID- 11523439
TI  - Toxic effect caused on microflora of soil by pesticide picloram application.
AB  - The toxic effect of the herbicide picloram on the microbial population of a
      typical Brazilian red Latosol soil was studied in a series of microcalorimetric
      experiments. The activity of the soil was stimulated by the addition of 6.0 mg of
      glucose and 6.0 mg of ammonium sulfate, under 34.8% controlled moisture, to a
      1.50 mg soil sample, at 298.15 +/- 0.02 K. The net thermal effect due to the
      addition of the picloram to the soil was determined by interpreting the power
      time curves, which were recorded on the microcalorimeter. The total thermal
      effect evolved by the microorganisms was affected by the increasing doses of
      herbicide, and varied from 0 to 10.00 micrograms g-1. An increase in picloram
      exposure caused a decrease of the original thermal effect, reaching a null value
      above 20.89 micrograms of herbicide per gram of soil. The decreases of the
      thermal effect evolved by microorganisms and the increase of the lag phase period
      are associated with the death of the microbial population. The effects caused by
      picloram application in this typical Brazilian soil resulted in a strong effect
      on the soil microbial communities.

PMID- 11523440
TI  - Effect of ultrasonic agitation on the release of copper, iron, manganese and zinc
      from soil and sediment using the BCR three-stage sequential extraction.
AB  - An ultrasonic bath and an ultrasonic probe have been used to develop rapid
      versions of the three-stage Community Bureau of Reference (BCR, now the
      Standards, Measurement and Testing Programme) sequential extraction procedure.
      The effect of the ultrasonic treatments on the extraction of copper, iron,
      manganese and zinc from a sewage sludge-amended soil has been assessed.
      Recoveries similar to those of conventional shaking (i.e., conventional value, +/
      30%) could generally be obtained for copper, manganese and zinc, but not for the
      important matrix element iron. With the use of compromise sonication conditions,
      steps 1, 2 and 3 of the sequential extraction (excluding the hydrogen peroxide
      digestion in step 3, which was not performed with sonication) could be completed
      in 3, 5 and 1 min, respectively, using the ultrasonic probe, and in 3, 1 and 1 h,
      respectively, using the bath. The extraction procedures developed using the soil
      performed well when applied to lake sediment BCR CRM 601. Analyte partitioning
      was generally similar to that obtained with mechanical shaking, and overall metal
      recoveries were 84-98% of those obtained with the conventional BCR protocol,
      except for copper extracted with the probe (74%). Poorer performance (analyte
      recoveries, 58-104%) was obtained when the methods were applied to an intertidal
      sediment. This highlights the difficulty of developing a version of the BCR
      extraction, with ultrasonic assistance, which gives a performance equivalent to
      conventional shaking when applied to different substrates.

PMID- 11523441
TI  - Comparison of response of six different luminescent bacterial bioassays to
      bioremediation of five contrasting oils.
AB  - The performance of six different bioluminescent bacteria for the assessment of
      oil bioremediation was compared. Three contained lux genes linked to promoters
      from hydrocarbon degradation pathways: Pseudomonas fluorescens HK44 (pUTK21),
      Escherichia coli HMS174 (pOS25) and E. coli DH5 alpha (pGEc74, pJAMA7),
      responding to naphthalene, isopropylbenzene and octane, respectively. The other
      three expressed lux constitutively: E. coli HB101 (pUCD607) and P. putida F1
      (pUCD607) are genetically engineered, while Vibrio fischeri is naturally
      bioluminescent and was included to facilitate comparison with previous work. Five
      different oils (four crude oils plus diesel) were spiked into soil, and the
      progress of remediation was followed over a period of 119 d by monitoring both
      hydrocarbon disappearance and changes in the microbial response to soil extracts.
      The octane bioassay was the only one of the hydrocarbon-responsive bacterial
      assays to show any appreciable response, with up to 20-fold induction by light
      crude oils. Heavy crude oil and diesel elicited a much weaker response. The
      metabolic (lux constitutively expressed) bioassays showed that there was a
      general increase in toxicity over the course of the experiment, although toxicity
      to E. coli HB101 (pUCD607) appeared to be decreasing by the final sampling point.
      The metabolic bioassay response was much less variable between the different oils
      than for the first three, catabolic, strains.

PMID- 11523442
TI  - Approaches to soil remediation by complexometric extraction of metal contaminants
      with regeneration of reagents.
AB  - Complexometric equilibrations were performed with six chelating reagents to
      mobilise Cu, Mn, Pb and Zn from a contaminated urban soil. The metal-laden
      aqueous extract was treated with sodium diethyldithiocarbamate (DEDTC) to
      precipitate the heavy metals from solution while liberating the chelating
      reagent. The aqueous supernatant fraction was then re-combined with the soil
      particulates to extract more pollutants. A sparing quantity of EDTA
      (ethylenediaminetetraacetic acid; 10 mmol) mobilised 32-54% of the 5 mmol of
      heavy metals from the soil with three cycles but only 0.1 and 1.0% of the iron
      and magnesium, respectively, was removed. Whereas DPTA (1,3-diamino-2
      hydroxypropane-N,N,N',N'-tetraacetic acid) and citric acid also mobilised each of
      the heavy metals to some extent and continued to extract these metals during all
      three cycles, the DTPA (diethylenetriamine pentaacetic acid), although efficient
      initially, could not be recycled with these conditions. ADA [N-(2
      acetamido)iminodiacetate] and SCMC [(S)-carboxymethyl-L-cysteine] were selective
      for copper and zinc but mobilised only Cu when recycled. An alternate means of
      regenerating the chelating reagent involved treatment of the aqueous extract with
      magnesium (Mg0) granules. Excess HEDC [bis(2-hydroxyethyl)dithiocarbamate]
      mobilised appreciable quantities (19-57%) of heavy metals from the soil and
      retained its complexing activity when recycled. An appreciable fraction of the
      mobilised Pb and Cu and a portion of the Zn were cemented to the surfaces of the
      excess magnesium whereas virtually all of the Fe and Mn was removed from solution
      as insoluble hydroxides.

PMID- 11523443
TI  - Recycling of petroleum-contaminated sand.
AB  - The environmental impact of using petroleum-contaminated sand (PCS) as a
      substitute in asphalt paving mixtures was examined. An appreciable component of
      PCS is oily sludge, which is found as the dregs in oil storage tanks and is also
      produced as a result of oil spills on clean sand. The current method for the
      disposal of oily sludge is land farming. However, this method has not been
      successful as an oil content of < 1% w/w is required, and difficulty was
      encountered in reaching this target. The reuse of the sludge in asphalt paving
      mixtures was therefore considered as an alternative. Standard tests and
      environmental studies were conducted to establish the integrity of the materials
      containing the recycled sludge. These included physical and chemical
      characterization of the sludge itself, and an assessment of the mechanical
      properties of materials containing 0%, 5%, 22% and 50% oily sludge. The blended
      mixtures were subjected to special tests, such as Marshall testing and the
      determination of stability and flow properties. The experimental results
      indicated that mixtures containing up to 22% oily sludge could meet the necessary
      criteria for a specific asphalt concrete wearing course or bituminous base
      course. To maximize the assay from the recycled material, the environmental
      assessment was restricted to the 50% oily sludge mixture. Leachates associated
      with this particular mixture were assayed for total organic residue and certain
      hazardous metal contaminants. The results revealed that the organics were
      negligible, and the concentrations of the metals were not significant. Thus, no
      adverse environmental impact should be anticipated from the use of the recycled
      product. Our research showed that the disposal of oily sludge in asphalt paving
      mixtures could possibly yield considerable savings per tonne of asphalt concrete,
      and concurrently minimize any direct impact on the environment.

PMID- 11523444
TI  - Recycling of paint-contaminated grit.
AB  - The impact on the environment of using paint-contaminated grit (PCG) as a partial
      or full replacement for sand in Portland cement mortar and asphalt concrete
      mixtures was investigated. The grit waste material originated from abrasive
      blasting of offshore steel structures. There is a major environmental concern
      regarding the safe disposal of the spent blasting abrasives that contain paint
      chips or paint particles and other debris removed from the surface of the steel
      structures. This work investigated the potential reuse of PCG in Portland cement
      concrete (PCC) and hot mix asphalt concrete. Several studies were conducted to
      establish the integrity of the materials containing the recycled grit. These
      included the chemical and physical characterization of natural sand and PCG, the
      assay of leaches associated with the grit material for hazardous metal
      contaminants, such as Cr, Cd and Pb, and the assessment of the mechanical
      properties of the PCG-substituted mortars by applying special tests (such as
      Marshall stability and determination of the flow properties) to the PCG
      substituted asphalt concrete mixtures. The overall results demonstrated that the
      potential reuse of PCG in PCC and asphalt concrete mixtures would not pose any
      environmental threat and could produce several benefits, such as reduced disposal
      costs, protection of water sources from improper disposal practices and reduced
      costs in the production of natural aggregates and asphalt cement.

PMID- 11523445
TI  - A proficiency testing scheme for aromatic hydrocarbons in air by the manual
      thermal desorption-GC method: a comparison of laboratory performance with the
      uncertainty requirements of the European Union Ambient Air Directive.
AB  - The Workplace Analysis Scheme for Proficiency (WASP) is a proficiency testing
      scheme for the analysis of occupational hygiene and environmental air samples and
      is operated in the UK by the Health and Safety Laboratory. Since 1997, WASP has
      offered samples of benzene, toluene and m-xylene, at environmental levels on
      Tenax, and has about 35 laboratories participating, mostly from industry, local
      government and consultancy organisations in the UK. The results reported cover
      the first 10 rounds of the environmental analytes (1997-1999) and demonstrate the
      important role of proficiency testing in assessing the quality of laboratory
      performance. Estimates are obtained for within-laboratory precision and the total
      variability at each analyte level. The estimates of within-laboratory precision
      suggest that laboratories have more difficulty analysing toluene and m-xylene
      than benzene. Linear relationships for the reproducibility relative standard
      deviation (RSDT) with loading level are evident for the analytes at occupational
      levels. At environmental levels, the relationship between loading level and
      reproducibility is much less well defined. The standard deviation for the
      proficiency testing assessment for all three analytes at the environmental level
      is 14%, as derived from the benzene data. Expanded uncertainty estimates (k =
      1.96), for the analysis of samples since the scheme started, are obtained from
      the average total variance, and are 27% for benzene, 39% for toluene and 36% for
      m-xylene. Although the linear trend of performance against round number was not
      significant at the 95% level of confidence (p = 0.23 for benzene, p = 0.3 for
      toluene and p = 0.32 for m-xylene), there was a general improvement in RSDT from
      26-34% to about 8-13% 10 rounds later. Currently, for a laboratory to meet one of
      the data quality objectives in the Ambient Air Directive (indicative measurement
      of benzene, expanded uncertainty +/- 30% or less), it would have to achieve a
      level of analytical performance to satisfy the category 1 (best performance)
      limit of better than +/- 8.8%. In the last proficiency testing round, discussed
      in this paper, only 58% of laboratories obtained performance scores that
      indicated that they were able to consistently achieve this level of performance.

PMID- 11523446
TI  - Determination of isocyanic acid in air.
AB  - A method is presented for the determination of isocyanic acid (ICA), HNCO, in air
      samples as a di-n-butylamine (DBA) derivative. The method is based on sampling in
      midget impinger flasks containing 10 ml of 0.01 mol l-1 DBA in toluene.
      Quantification was made using liquid chromatography (LC) and electrospray mass
      spectrometry (MS) monitoring positive ions. The instrumental detection limit for
      the LC-MS was 10 fmol of ICA-DBA. ICA was generated by thermal decomposition of
      urea. A standard solution containing the DBA derivatives of ICA was prepared by
      collecting the emitted ICA in an impinger flask containing DBA. ICA in the
      reference solution was characterised by LC and time-of-flight (TOF) MS and
      quantified by LC chemiluminescent nitrogen detection (LC-CLND). The instrumental
      detection limit for the LC-CLND was 1 ng of nitrogen. ICA was emitted during
      thermal degradation of PFU resins and polyurethane (PUR) lacquers, from car metal
      sheets. ICA was the most dominant isocyanate and in PUR coating up to 8% of the
      total weight was emitted as ICA and for PFU resins up to 14% was emitted as ICA.
      When air samples were collected in an iron foundry during casting in sand moulds
      with furan resins, concentrations of ICA in the range 50-700 micrograms m-3 were
      found in the working atmosphere.

PMID- 11523447
TI  - Analysts in miniature.

PMID- 11523449
TI  - Pesticide regulation, product innovation and public attitudes.

PMID- 11523450
TI  - Radiology's new realms.

PMID- 11523451
TI  - The emergency room of the old Minneapolis General Hospital.

PMID- 11523452
TI  - Foreign exchanges.

PMID- 11523453
TI  - Health care planning for chemical and biological terrorism.

PMID- 11523454
TI  - Telemedicine in Minnesota. A primer for physicians.

PMID- 11523455
TI  - Consider schistosomiasis.

PMID- 11523456
TI  - Educator in an exploding field.

PMID- 11523457
TI  - The basics of new treatment for chronic hepatitis C.

PMID- 11523458
TI  - Hemotympanum from trauma.

PMID- 11523459
TI  - Trans-canine-fossa maxillary sinoscopy for biopsy via the Stammberger technique.

PMID- 11523460
TI  - Vascular abnormalities involving the vibratory margin of the vocal fold.

PMID- 11523461
TI  - ENG in 16-year-old with a history of dizziness since early childhood.

PMID- 11523462
TI  - Trigeminal neuropathy secondary to a meningioma.

PMID- 11523463
TI  - Distal esophageal diverticulum secondary to a reflux-induced stricture.

PMID- 11523464
TI  - On being a happy surgeon.

PMID- 11523465
TI  - Malignancy of the larynx in a child.
AB  - Squamous cell carcinoma of the larynx in children is rare. The management of
      laryngeal malignancy is more difficult in children than adults for several
      reasons: the aggressive nature of a tumor that is often diagnosed late in
      children; the delicacy of pediatric anatomic structures; intraoperative blood
      loss; long-term post-treatment complications; and psychological factors
      particular to children. A tracheostomized 13-year-old boy came to us with a 4
      month history of hoarseness, breathing difficulty, and swelling in the neck. A
      detailed examination revealed that a transglottic tumor had infiltrated the
      thyroid and cricoid cartilage, the upper two tracheal rings, and the thyroid
      gland. Such an infiltration has not been previously reported. The lesion proved
      to be a well-differentiated squamous cell carcinoma. We performed a wide-field
      total laryngectomy, which was followed by radiotherapy. Unfortunately, the child
      survived only 3 years postoperatively.

PMID- 11523466
TI  - Repair of a large septal perforation with a radial forearm free flap: brief
      report of a case.
AB  - We treated a 38-year-old man who had a large septal perforation that had been
      caused by chronic nasal inhalation of cocaine. We were able to repair the
      perforation with a left radial forearm free flap. Long-term followup indicates a
      successful closure of the defect and a natural thinning of the flap. The patient
      remains symptom-free more than 2 years following surgery.

PMID- 11523467
TI  - Effectiveness of the ultrasonic harmonic scalpel for tonsillectomy.
AB  - The Ultracision harmonic scalpel (UHS) cuts and coagulates tissue with high
      frequency ultrasound. We describe the results of our use of the UHS to perform
      tonsillectomies in 59 patients. The mean operative blood loss was 7 ml (range: 0
      to 75); 56% of patients experienced no measurable blood loss. The mean length of
      operating time was 8 minutes and 10 seconds (range: 3:45 to 20:25). Patients were
      assessed for 2 weeks for postoperative pain on the basis of a 10-point linear
      analog scale. The mean pain score on postoperative day 1 was 4.7; the score
      peaked at 6.0 on day 4 and fell to less than 3.0 by day 11. Patients returned to
      full function in an average of 10.9 days (range: 3 to 15). Three patients
      experienced secondary hemorrhage, one of whom required surgical intervention. We
      found the UHS to be a well-designed and easy-to-use instrument. Operating time
      was short, blood loss was minimal, and the degree of early postoperative pain was
      low. We believe that our findings are encouraging and that the UHS might well
      have a place in the surgical armamentarium for tonsillectomy.

PMID- 11523468
TI  - A metal ring that had been lodged in a child's nasopharynx for 4 years.
AB  - A considerable number of articles on foreign-body ingestion and inhalation have
      been reported in the literature. Of these, nasopharyngeal foreign bodies are
      rare. Unless they cause total obstruction, symptoms typically appear late.
      Foreign bodies, especially metal ones, can lodge in soft tissue, and their
      removal can be rather complicated. In this article, we describe the case of a 4
      year-old girl who had had a gold ring lodged in her nasopharynx. The history led
      us to determine that the ring had been there since the child was 3 months old. A
      flexible fiberoptic nasopharyngeal examination revealed that the ring was
      embedded in the nasal surface of the soft palate and was enclosed by a thin layer
      of mucosal membrane. With the patient under general anesthesia, we were able to
      remove the foreign body with a 0 degree endoscope.

PMID- 11523469
TI  - Treatment of chronic suppurative otitis media with Broncasma Berna.
AB  - Broncasma Berna, an inactivated bacterial vaccine, has been safely used
      throughout the world for 30 years for the prevention or treatment of various
      infectious processes. Until now, there has been no published report regarding its
      use as a treatment for chronic suppurative otitis media. In this small study,
      five such patients (median age: 57 years) underwent a series of seven 0.05-ml
      injections of Broncasma Berna. In all cases, their otorrhea diminished markedly
      and their tympanic membranes were almost completely dry. The cost of treatment
      was extremely low.

PMID- 11523470
TI  - Unilateral versus bilateral neck exploration in parathyroid surgery: an
      assessment of 55 cases.
AB  - We retrospectively evaluated the cases of 55 patients who had undergone surgery
      for primary hyperparathyroidism at our institution to determine whether their
      parathyroid glands were abnormal on both sides. Thirty-six of these patients had
      undergone a bilateral neck exploration, and 19 had had a unilateral
      investigation. Of the 36 bilaterally explored patients, 30 had a solitary adenoma
      and no parathyroid pathology on the opposite side, five patients had hyperplastic
      glands with more than one gland involved, and one patient had two adenomas. In
      the unilaterally explored group, all 19 patients had a solitary adenoma. There
      were no failures in the way of persistent hypercalcemia in either group. Based on
      our findings, we conclude that a unilateral neck exploration should be performed
      during surgery for primary hyperparathyroidism whenever a large parathyroid
      adenoma and a normal parathyroid gland are found on the same side. Bilateral
      exploration should be reserved for patients in whom pathology cannot be found on
      the initially explored side during surgery and for patients who have obvious
      parathyroid hyperplasia.

PMID- 11523471
TI  - Intra- and intersession reliability of acoustic rhinometry in measuring nasal
      cross-sectional area.
AB  - We evaluated the intrasession and intersession reliability of acoustic rhinometry
      in measuring nasal cross-sectional areas in 10 subjects. Subjects were measured
      under three conditions: with a Breathe Right nasal strip in place, with a sham
      strip in place, and with no strip in place. Two sets of three measurements were
      taken 1 week apart. The intrasession reliability both with and without the
      Breathe Right strip was very good (intraclass correlation coefficient [ICC]
      [2,1]: 0.97 and 0.98, respectively). The intersession reliability with and
      without the Breathe Right strip was not nearly as good (ICC [2,1]: 0.62 and
      0.67). The Breathe Right strip increased the mean nasal cross-sectional area by
      0.10 cm2 (17.4%). We conclude that acoustic rhinometry is a reliable way to
      measure nasal cross-sectional area during a single session of multiple tests, but
      it is not as reliable across sessions. We also determined that the Breathe Right
      nasal strip significantly increases nasal cross-sectional area.

PMID- 11523472
TI  - The treatment of allergic rhinitis with immunotherapy: a review of 1,000 cases.
AB  - We conducted a 10-year retrospective chart review of 1,000 immunotherapy-treated
      patients to evaluate the efficacy and safety of serial dilution quantitative
      intradermal testing in the management of allergic rhinitis. Three months after
      the initiation of immunotherapy, these patients had been assessed to ascertain
      whether or not they had experienced any overall improvement in their initial
      symptoms. Also included in this evaluation were determinations of each patient's
      use of medications as well as the incidence of adverse reactions to treatment and
      recurrent sinus infections. We found that 860 patients had achieved complete
      relief of their symptoms and required no other treatment; the remaining 140
      patients experienced a partial improvement and continued to use pharmacotherapy
      to control breakthrough symptoms. During skin testing, only one patient
      experienced a systemic reaction, which responded to subcutaneous epinephrine.
      There were no deaths. We conclude that serial dilution quantitative intradermal
      testing is safe and that quantification of skin reactivity in evaluating and
      treating allergic rhinitis with immunotherapy is completely effective in the vast
      majority of patients.

PMID- 11523473
TI  - Evaluation of post-tonsillectomy bleeding in the adult population.
AB  - A retrospective review of a consecutive series of 685 adult patients undergoing
      tonsillectomy was conducted. Determinations were made of the post-tonsillectomy
      bleeding rate, the need for intervention to control bleeding, and the blood
      transfusion rate. Statistical analysis was used to determine whether bleeding
      rates differed according to three criteria: gender, indication for tonsillectomy,
      and age. Post-tonsillectomy bleeding occurred in 35 patients (5.1%); five of
      these patients experienced bleeding during the first 24 hours postoperatively,
      and the remaining 30 experienced delayed bleeding. When it occurred, the mean
      time lapse between tonsillectomy and bleeding was 6.9 days (+/- 4.1). Twenty of
      the 35 patients (57.1%) required a procedure to control their bleeding, but no
      patient required a transfusion. There was no statistically significant difference
      in bleeding rates based on gender, the indication for surgery (chronic
      tonsillitis, obstructive sleep apnea syndrome, or to rule out neoplasia), and
      age. These results indicate that (1) post-tonsillectomy bleeding occurs in
      approximately 1 of 20 adults independent of individual patient characteristics,
      (2) more than half of patients who bleed are likely to require a procedure to
      control their hemorrhage, and (3) the need for transfusion is distinctly
      unlikely.

PMID- 11523474
TI  - Cost-effectiveness of two types of dysphagia care in head and neck cancer: a
      preliminary report.
AB  - We conducted a prospective, preliminary study to compare the cost-effectiveness
      of two different instrument-based techniques for diagnosing and managing
      dysphagia in 30 consecutive hospitalized patients with head and neck cancer. The
      two techniques are videofluoroscopy via modified barium swallow (MBS) and
      videoendoscopy via flexible endoscopic evaluation of swallowing with sensory
      testing (FEESST). Medicare was the primary insurer of all patients. Fifteen of
      these patients had their dysphagia diagnosed and managed by MBS and the other 15
      by FEESST. Cost-effectiveness was assessed by determining the average Medicare
      reimbursement for each procedure. We found that the mean reimbursements were
      $451.01 (+/- $50.55) for MBS and $321.23 (+/- $3.01) for FEESST. The mean
      reimbursement for FEESST was significantly lower than that for MBS (p < 0.0001;
      Mann-Whitney U test). We conclude that FEESST appears to be more cost-effective
      than MBS for the inpatient management of dysphagia in patients with head and neck
      cancer.

PMID- 11523475
TI  - Malignant fibrous histiocytoma arising in the upper posterior triangle of the
      neck.
AB  - We describe the case of a 59-year-old man who came to us with a right neck mass
      of 4 to 5 months' duration. A histologic diagnosis of malignant fibrous
      histiocytoma was made, and the patient underwent wide local excision and neck
      dissection followed by postoperative radiation therapy. We briefly discuss the
      characteristics and treatment of this rare entity.

PMID- 11523476
TI  - Chondrosarcoma of the larynx: a therapeutic challenge.
AB  - The diagnosis of laryngeal chondrosarcoma is likely to be missed because of its
      infrequent occurrence and its indolent pattern of growth. A 53-year-old woman
      came to our service with an 18-year history of hoarseness and increasing dyspnea.
      She had been previously documented as having left vocal fold paralysis and a
      bulging laryngeal mass. Computed tomography revealed the presence of a large
      calcified tumor that had caused a deformity of the larynx and an erosion of the
      arytenoid and cricoid cartilages. Direct laryngoscopy detected a large
      supraglottic mass with a normal-appearing mucosa. Total excision of the tumor was
      achieved through a lateral neck incision that spared the larynx. This case
      emphasizes the importance of a high index of suspicion for laryngeal
      chondrosarcoma in a patient who has unexplained vocal fold paralysis and a
      submucosal subglottic mass. Every effort should be made to take a conservative
      surgical approach that preserves laryngeal function when possible.

PMID- 11523477
TI  - Detection of sinus-induced orbital mycosis with standardized orbital
      ultrasonography: a case report.
AB  - Fungal involvement of the paranasal sinuses is frequently observed in the
      immunocompromised host, and it can become life-threatening if it is not
      diagnosed. Although the definitive diagnosis is made by tissue biopsy and
      culture, imaging is of vital importance in the clinical workup and in planning
      treatment. We present a case of fulminant ethmoidal sinusitis caused by
      Aspergillus flavus with orbital involvement in an immunocompromised patient.
      Standard computed tomography of the paranasal sinuses was complemented by the use
      of standardized orbital ultrasonography, which was able to identify the
      intraorbital extension. We discuss the role of standardized orbital
      ultrasonography as a complementary imaging modality in the diagnosis of fungal
      sinusitis and in the assessment of local extension. To the best of our knowledge,
      the role of SOU in diagnosing an orbital extension of a fungal infection of the
      paranasal sinuses has not been previously discussed in the literature.

PMID- 11523478
TI  - Stapes mobilization in otosclerosis.
AB  - We performed a retrospective chart study (including surgeon's notes and
      audiometric results) and an analysis of the archival temporal bones from a
      patient who had undergone surgery for stapes mobilization in both ears. The
      stapes footplate was submerged into the vestibule on the right (as a complication
      of surgery) and absent on the left. One interesting finding was that the
      patient's hearing had improved on the right despite the presence of the depressed
      footplate and that the air-bone gap had widened on the left despite the absence
      of complications on that side.

PMID- 11523479
TI  - Childhood vertigo: a case report and review of the literature.
AB  - Vertigo is a relatively uncommon pediatric complaint, with correct diagnosis made
      even more challenging by the patient's inherent difficulty in describing his or
      her symptoms. Confusion may exist among vertigo, dizziness, dysequilibrium,
      ataxia, pre-syncope or syncope, and seizure activity by both the pediatric
      patient and his or her family. A complete history and physical examination, as
      well as appropriate ancillary studies, may assist in clarifying the diagnosis.
      This paper attempts, via case report and literature review, to discuss the
      various etiologies of acute vertigo in the pediatric population, provide
      diagnostic clues, and evaluate some of the available diagnostic modalities.

PMID- 11523480
TI  - Touching.

PMID- 11523481
TI  - Culturally competent care.
AB  - OBJECTIVES: To define key concepts and summarize available guidelines that are
      important resources to assist nurses to provide culturally competent care. DATA
      SOURCES: Medline, anthropologic and epidemiologic literature, and National
      Institutes of Health documents. CONCLUSIONS: Controversy remains about the most
      appropriate language to use to describe features of diverse populations.
      IMPLICATIONS FOR NURSING PRACTICE: Becoming culturally competent begins by
      understanding terms and concepts that are essential in developing cultural
      awareness, knowledge, and skills. Sensitivity to language and the history of the
      development of some labels are important.

PMID- 11523482
TI  - Screening and early detection among racial and ethnic minority women.
AB  - OBJECTIVES: To highlight sociocultural factors reported to influence and
      strategies to promote breast and cervical cancer screening and early detection
      behaviors of racial and ethnic minority women. DATA SOURCES: Published articles,
      book chapters, and reports. CONCLUSIONS: The most successful strategies for
      promoting screening and early detection among racial and ethnic minority women
      are collaborative and include approaches that are culturally sensitive and
      appropriate. NURSING IMPLICATIONS: Intercultural and intracultural differences in
      racial and ethnic minority women challenge nurses to explore strategies that
      focus on the health care provider, the health care delivery system, and the
      individual woman within the context of the woman's culture.

PMID- 11523483
TI  - Cancer support groups: meeting the needs of African Americans with cancer.
AB  - OBJECTIVES: To describe culturally appropriate ways that cancer support groups
      can meet the needs of African Americans with cancer. DATA SOURCES: Research
      articles and clinical experience. CONCLUSIONS: Support groups are an important
      vehicle through which people cope with the emotional and physical impact of their
      cancer. Most support group participants are middle-class, white women. Faith
      based cancer support groups can address the needs of many African Americans with
      cancer by offering support and education within the context of a spiritually
      based life-style. IMPLICATIONS FOR NURSING PRACTICE: Coping strategies may vary
      among cultural groups. In order to be supportive, cancer support groups must be
      congruent with the values and beliefs of the group's members.

PMID- 11523484
TI  - Cultural beliefs of Asian Americans associated with terminal illness and death.
AB  - OBJECTIVES: Cultural competence often focuses on the skills of the professional;
      whereas, this article focuses on the needs of the patient. DATA SOURCES: Research
      studies, review articles, book chapters, and clinical practice. CONCLUSIONS:
      Patients benefit from health care professionals that are attuned and able to
      nurture patients in a process of identifying their needs regarding terminal
      illness and death. The health care professional's ability and sensitivity to be
      culturally aware, knowledgeable, and open directly influences the patient's
      quality of life and death. IMPLICATIONS FOR NURSING PRACTICE: As the population
      becomes more diverse, health care professionals must develop cultural competence
      to add value to themselves, the profession of nursing, and health care in the
      future.

PMID- 11523485
TI  - Qualitative research with diverse populations.
AB  - OBJECTIVES: To describe the benefits of conducting qualitative research with
      members of diverse cultures. DATA SOURCES: Research studies, articles and books
      on philosophy of science. CONCLUSIONS: Qualitative research with diverse
      populations is useful when little research exists on a topic, when there are no
      reliable and valid instruments for the groups, and when the appropriate language
      to use or the appropriate concepts and questions to ask are unclear.
      Participating in research that includes discussing your experiences has also been
      found to be valuable to those participating. IMPLICATIONS FOR NURSING PRACTICE:
      Qualitative studies with diverse groups are needed to understand the concepts
      that are important to members of these groups, and to guide us in asking the
      correct questions using correct language.

PMID- 11523486
TI  - Spirituality, culture, and cancer care.
AB  - OBJECTIVES: To explore the inter-relatedness of culture and spirituality in the
      context of cancer caregiving and to provide suggestions for improving clinical
      practice. DATA SOURCES: Research reports and theoretical and clinical papers from
      nursing and medicine. CONCLUSION: Understanding spiritual-cultural influences
      that affect responses to cancer are essential if a nurse is to provide effective
      care. Research has documented spiritual-cultural aspects of cancer prevention and
      screening, living and coping with cancer, and dying with cancer. This research
      suggests that African American and Hispanic cancer patients are more religious,
      recognize more spiritual needs, and benefit more from religious coping
      strategies, than do white Americans. IMPLICATIONS FOR NURSING PRACTICE:
      Strategies proposed for increasing a nurse's effectiveness while caring for
      clients with diverse spiritual-cultural beliefs and behaviors include: increasing
      awareness of personal spiritual-cultural values and beliefs, gaining knowledge
      about diverse religious traditions, and negotiation with clients when values and
      beliefs that compromise care conflict.

PMID- 11523487
TI  - Native American cultural aspects of oncology nursing care.
AB  - OBJECTIVE: To explain challenges Native American cancer patients experience
      throughout the continuum of cancer care. DATA SOURCE: Preliminary findings from
      the Native American Cancer Survivors Support Network, summaries from focus groups
      with Native American cancer survivors, and literature review. CONCLUSIONS:
      Cultural and family issues are diverse and affect cancer care situation in many
      different ways. IMPLICATIONS FOR NURSING PRACTICE: The oncology nurse needs to
      understand and respect the diversity among Native American cancer patients and to
      help the patient and provider find ways to allow for the inclusion of family
      members, spirituality, and traditional Indian medicine within the Western medical
      treatment model.

PMID- 11523488
TI  - Making inroads on cancer prevention and control with Asian Americans.
AB  - OBJECTIVES: To describe cancer incidence and mortality rates, risk factors, and
      some of the cancer screening and control programs for the Asian American
      population. DATA SOURCES: Medline, National Cancer Institute publications,
      textbooks, and census data. CONCLUSIONS: Progress has been made but much needs to
      be done in cancer prevention and control to lessen the cancer burden among Asian
      Americans. The diversity of this population requires a variety of strategies to
      influence cancer screening and control. IMPLICATIONS FOR NURSING PRACTICE: Health
      professionals need to understand how Asian cultures perceive health, diseases,
      and treatments. While efforts should be made to provide correct information about
      cancer screening and control measures, respect for different beliefs, values, and
      perceptions must be conveyed to build trust.

PMID- 11523489
TI  - Be ready to manage chronic obstructive pulmonary disease.

PMID- 11523490
TI  - Patient care by physician assistants and by physicians in an emergency
      department.
AB  - OBJECTIVE: Decreasing health care dollars have resulted in increased utilization
      of so-called midlevel practitioners. We compared emergency physicians with
      emergency department physician assistants (PAs) to determine whether PAs are an
      appropriate option for providing services rendered by physicians in this setting.
      METHODS: We undertook an observational retrospective review of a hospital
      database (July 1995 to June 1996) from an urban urgent-care facility. Collection
      of data was restricted to times of single-provider coverage. Every patient who
      visited the clinic was seen by the sole provider (physician or PA) on duty; no
      one was turned away. If a patient needed emergency care, he (or she) was
      transferred to the main emergency department at the hospital, as deemed
      appropriate by either provider after evaluation. Physicians and PAs were compared
      in regard to length of visit and total charges in 14 diagnostic groups. Adverse
      outcomes were not evaluated. Age, sex, race, and multiple diagnoses were
      controlled for by regression analysis. RESULTS: A total of 9,601 patient
      encounters were analyzed. PAs and physicians had a similar distribution of
      diagnostic groups. Respiratory infection and musculoskeletal disorders accounted
      for approximately 36% of visits; lacerations, gastrointestinal disorders, and
      otitis each accounted for 5% of visits. Overall, visits were 8 minutes longer and
      total charges $8 less when a patient was treated by a PA. Patients who had
      headache, otitis, respiratory infection, asthma, gastrointestinal or
      genitourinary disorder, cellulitis, laceration, or other musculoskeletal disorder
      had a longer visit when seen by a PA; the difference ranged from 5 to 32 minutes
      longer. In no diagnostic group was there a statistically significant greater
      length of visit or total charge because patients were seen by a PA. CONCLUSION:
      Despite a few large differences in some diagnostic groups, the two types of
      provider had, overall, small but clinically insignificant differences in length
      of visit and total charges. The magnitude of difference in length of visit and
      total charges strongly suggests that PAs, when compared with physicians, are a
      viable staffing option in an urgent care facility.

PMID- 11523491
TI  - Getting past the obvious in an ED case of altered mental status and ECG changes.

PMID- 11523492
TI  - The job at hand. Forging strategic relations with organized medicine.

PMID- 11523493
TI  - Electroconvulsive therapy. Potent intervention for the troubled mind.

PMID- 11523494
TI  - Considering nasal corticosteroids to treat allergic rhinitis.

PMID- 11523495
TI  - Changing the behavior of our patients.

PMID- 11523496
TI  - The complexities of treating shoulder pain.

PMID- 11523497
TI  - The stages of change for dietary fat and fruit and vegetable intake of patients
      at the outset of a cardiac rehabilitation program.
AB  - PURPOSE: To determine the stages of change for dietary fat and fruit and
      vegetable intake of cardiac patients entering a rehabilitation program. DESIGN: A
      cross-sectional study using a convenience sample of newly admitted cardiac
      rehabilitation patients. SETTING: Department of Pulmonary and Cardiac
      Rehabilitation, Moses H. Cone Memorial Hospital, Greensboro, North Carolina.
      SUBJECTS: Subjects (n = 226) were predominantly men, Caucasian, married, smokers
      with 9 to 12 years of education, and with primary diagnoses of coronary artery
      bypass graft. MEASURES: Stages of change and food frequency questionnaires were
      completed by subjects upon admission to cardiac rehabilitation. RESULTS: Subjects
      in action and maintenance stages for dietary fat reduction comprised 78.7% of the
      population. Subjects' percentage of energy from fat decreased linearly from the
      precontemplation stage (38.8%) to the maintenance stage (30.9%). Eighty-one
      percent of subjects were in precontemplation/contemplation for increasing fruit
      and vegetable intake. Daily servings of fruits and vegetables ranged from 2.6 for
      precontemplation to 5.1 for maintenance subjects. Age, body mass index (BMI),
      education, and family history for coronary disease were unrelated to stage of
      change for the dependent variables. CONCLUSIONS: Patients were in different
      stages of change for two nutritional behaviors linked to the same disease.
      Results support the need to assess patients for food behaviors and apply
      different educational interventions for each food behavior.

PMID- 11523498
TI  - Social influences, social norms, social support, and smoking behavior among
      adolescent workers.
AB  - PURPOSE: To examine the relationships between worksite interpersonal influences
      and smoking and quitting behavior among adolescent workers. DESIGN: The cross
      sectional survey assessed factors influencing tobacco use behavior. SETTING:
      During the fall of 1998, data were collected from 10 grocery stores in
      Massachusetts that were owned and managed by the same company. SUBJECTS: Eligible
      participants included 474 working adolescents ages 15 to 18. Eighty-three percent
      of workers (n = 379) completed the survey. MEASURES: The self-report
      questionnaire assessed social influences, social norms, social support,
      friendship networks, stage of smoking and quitting behavior, employment patterns,
      and demographic factors. RESULTS: Thirty-five percent of respondents were never
      smokers, 21% experimental, 5% occasional, 18% regular, and 23% former smokers.
      Using analysis of variance (ANOVA), results indicate that regular smokers were
      30% more likely than experimental or occasional smokers to report coworker
      encouragement to quit (p = .0002). Compared with regular smokers, never smokers
      were 15% more likely to report greater nonacceptability of smoking (p = .01). chi
      2 tests of association revealed no differences in friendship networks by stage of
      smoking. CONCLUSIONS: These data provide evidence for the need to further explore
      social factors inside and outside the work environment that influence smoking and
      quitting behavior among working teens. Interpretations of the data are limited
      because of cross-sectional and self-report data collection methods used in one
      segment of the retail sector.

PMID- 11523499
TI  - Evaluation of a Wellness-Based Mindfulness Stress Reduction intervention: a
      controlled trial.
AB  - PURPOSE: To determine if participation in a Wellness-Based Mindfulness Stress
      Reduction intervention decreases the effect of daily hassles, psychological
      distress, and medical symptoms. DESIGN: A randomized controlled trial of a stress
      reduction intervention with a 3-month follow-up. SETTING: A university setting in
      West Virginia. SUBJECTS: A total of 103 adults, with 59 in the intervention group
      and 44 in the control group. Eight-five percent of subjects completed the
      intervention. Fifty-nine percent and 61% of the intervention and control subjects
      completed the study, respectively. INTERVENTION: The intervention consisted of an
      8-week group stress reduction program in which subjects learned, practiced, and
      applied "mindfulness meditation" to daily life situations. The control group
      received educational materials and were encouraged to use community resources for
      stress management. MEASURES: The Daily Stress Inventory assessed the effect of
      daily hassles, the Revised Hopkins Symptom Checklist measured psychological
      distress, the Medical Symptom Checklist measured number of medical symptoms, and
      a Follow-up Questionnaire measured program adherence. RESULTS: Intervention
      subjects reported significant decreases from baseline in effect of daily hassles
      (24%), psychological distress, (44%), and medical symptoms (46%) that were
      maintained at the 3-month follow-up compared to control subjects (repeated
      measures analysis of variance [ANOVA]; p < .05). CONCLUSIONS: Self-selected
      community residents can improve their mental and physical health by participating
      in a stress reduction intervention offered by a university wellness program.

PMID- 11523500
TI  - Engaging ethnically diverse teens in a substance use prevention advocacy program.
AB  - Teen Activists for Community Change and Leadership Education is designed to
      engage high school students living in low-income neighborhoods in community
      advocacy efforts to transform their schools and communities so they do not
      reinforce use of alcohol, tobacco, and other drugs. This nine month intervention
      for 116 freshmen and sophomores in and near San Jose, California consisted of 30
      90 minute meetings. Social cognitive constructs of sense of community, perceived
      self-efficacy, outcome expectancies, incentive value, policy control, and
      leadership competence guided the program. No changes in individual use of
      alcohol, tobacco, and other drugs were observed by the end of the program, but
      improvements in community involvement and self-perception of many of the
      constructs were observed.

PMID- 11523501
TI  - The value of leadership in implementing and maintaining a successful health
      promotion program in the Naval Surface Force, U.S. Pacific Fleet.
AB  - A health promotion program called the "Green H Award" was implemented in 1996 for
      the SURFPAC commands, which represented 35,000 Navy and Marine personnel serving
      in the Naval Surface Force of the U.S. Pacific Fleet, in an effort to reduce
      rates of smoking, alcohol abuse, obesity, and poor fitness. Commands which had
      leadership involvement in their health promotion effort had higher levels of
      implementation, success, and maintenance. Measures of all these health risks
      improved substantially between 1996 and 1999; however, the response rates for the
      measures was highly variable.

PMID- 11523502
TI  - [Solitary mastocytoma associated with newborn infants' identification bracelets].
AB  - We report the case of solitary mastocytoma, which appeared under the
      identification bracelet on the left wrist of a 2-day-old newborn infant. Stroking
      the lesion elicited Darier's sign. Histopathologic examination of a punch biopsy
      specimen revealed a dense mast cell infiltrate of the dermis, which was confirmed
      by Giemsa and toluidine blue stains. We believe that this case represents and
      unusual reactive process.

PMID- 11523503
TI  - [Epstein-Barr virus myopericarditis simulating acute myocardial infarction].

PMID- 11523504
TI  - [Prevalence of positive Mantoux in a population of 1,016 Saharan children between
      the ages of 3 and 6 years].

PMID- 11523505
TI  - [Smoking in pediatrics].

PMID- 11523506
TI  - [Cerebral edema in a newborn infant with diabetic ketoacidosis].

PMID- 11523507
TI  - [Continuance of breast-feeding].

PMID- 11523508
TI  - [What does influence decisions about breastfeeding?].

PMID- 11523509
TI  - [Importance of influenza in the child. Intranasal influenza vaccine: another
      systematic vaccination?].

PMID- 11523510
TI  - [Incorrect dosage in the use of inhaled desmopressin associated with convulsions
      due to hypnatremia].

PMID- 11523511
TI  - [Altadis again directs its advertising at young people: now on the Internet].

PMID- 11523512
TI  - [The need to validate arm measurements in newborn infants].

PMID- 11523514
TI  - Bibliography. Current world literature. Anabolic and catabolic signals.

PMID- 11523513
TI  - Pediatric Emergency Medicine Fellowship Programs.

PMID- 11523515
TI  - Stocking opioids in community pharmacies.

PMID- 11523516
TI  - Re: Economic evaluation of the fentanyl transdermal system.

PMID- 11523517
TI  - Re: Economic evaluation of fentanyl.

PMID- 11523518
TI  - Bibliography. Current world literature. Endoscopic surgery.

PMID- 11523519
TI  - Has resistance spread to the community?

PMID- 11523520
TI  - MRSA and MRSE: is there an answer?

PMID- 11523521
TI  - Extended-spectrum beta-lactamases: how big is the problem?

PMID- 11523522
TI  - Is there a need for new antifungal agents?

PMID- 11523523
TI  - Is the use of narrow-spectrum antibiotics too narrow-minded in the treatment of
      severe infections?

PMID- 11523524
TI  - Novel mechanisms of the transendothelial migration of leukocytes.

PMID- 11523525
TI  - IL-10 and its homologs: important immune mediators and emerging immunotherapeutic
      targets.

PMID- 11523526
TI  - [Frontotemporal dementia with marked character change].

PMID- 11523527
TI  - [Esophageal stenosis 5 months after irradiation of a central bronchial
      carcinoma].

PMID- 11523528
TI  - Propensity of fluoroquinolones with different moieties at position 8 to cause
      resistance development in clinical isolates of Streptococcus pneumoniae.

PMID- 11523529
TI  - Effects of moxifloxacin on neutrophil phagocytosis, burst production, and killing
      as determined by a whole-blood cytofluorometric method.

PMID- 11523530
TI  - A gas chromatography/high-resolution mass spectrometry (GC/HRMS) method for
      determination of polybrominated diphenyl ethers in fish.
AB  - A method for the determination of polybrominated diphenyl ethers (PBDEs) in biota
      for routine analysis is described. The mass spectroscopic (MS) evaluation of 23
      brominated diphenyl ethers, under electron ionization and electron capture
      negative ion conditions using magnetic sector and quadrupole mass spectrometers,
      showed that high-resolution mass spectrometry (HRMS) under electron ionization
      conditions was the most reliable technique, with high selectivity and adequate
      sensitivity. The instrument detection limit for this method ranged for individual
      congeners between 4.8 and 0.1 pg for 3-bromodiphenyl ether (BDE-2) and 2,3',4,4'
      tetrabromodiphenyl ether (BDE-66), respectively, and method detection limit for
      each homologue group ranged between 5 pg/g for salmon certified reference
      material (CRM) and 93 pg/g for lake trout CRM. The effectiveness of this method
      was evaluated by analyzing the occurrence of PBDEs in commercially available CRMs
      comprising Lake Ontario lake trout, Pacific herring, and sockeye salmon. The
      average coefficients of variation for the replicate analyses of PDBEs in several
      tissue samples were: 25% for lake trout, 36% for Pacific herring, and 34% for
      sockeye salmon. The average deviations in the inter-laboratory study were: 14%
      for lake trout, 15% for Pacific herring, and 37% for sockeye salmon. Results
      indicated that the described method, based on gas chromatography/high-resolution
      mass spectrometry, is reliable for determining PBDE concentrations in biological
      tissues.

PMID- 11523532
TI  - Influence of the menstrual cycle on flight simulator performance after alcohol
      ingestion.
AB  - OBJECTIVE: Previous studies investigating the influence of the menstrual cycle on
      cognitive functioning of women after alcohol ingestion have obtained inconsistent
      results. The present study tested the hypothesis that flight simulator
      performance during acute alcohol intoxication and 8 hours after drinking differs
      between the menstrual and the luteal phase of the menstrual cycle. METHOD: White
      female pilots (N = 24) were tested during the menstrual and the luteal phases of
      their menstrual cycles. On each test day they performed a baseline simulator
      flight, consumed 0.67 g/kg ethanol, and performed an acute-intoxication and an 8
      hour-carryover simulator flight. RESULTS: Subjects reached highly significant
      increases in estradiol (E2) as well as progesterone (P) levels during the luteal
      test day. Yet, there were no significant differences in overall flight
      performance after alcohol ingestion between the menstrual and luteal phases
      during acute intoxication or at 8-hour carryover. We found no correlations
      between E, or P levels and overall flight performance. However, there was a
      statistically significant Phase x Order interaction: Pilots who started the
      experiment with their menstrual day were less susceptible to the effects of
      alcohol during the second test day than were pilots who started with their luteal
      day. CONCLUSIONS: The tested menstrual cycle phases and varying E2 and P levels
      did not significantly influence postdrink flight performance. Because the present
      study included a comparatively large sample size and because it involved complex
      "real world" tasks (piloting an aircraft), we believe that the present findings
      are important. We hope that our failure to detect menstrual cycle effects will
      encourage researchers to include women in their investigations of alcohol effects
      and human performance.

PMID- 11523531
TI  - Increased levels of tissue plasminogen activator antigen and factor VIII activity
      in nonvalvular atrial fibrillation: relation to predictors of thromboembolism.
AB  - INTRODUCTION: Given that nonvalvular atrial fibrillation (AF)-associated stroke
      can be either cardioembolic or atherothrombotic, we investigated the
      relationships between nonvalvular AF and hemostatic factors reflecting intrinsic
      thrombogenic and atherogenic potentials (tissue plasminogen activator [t-PA]
      antigen, plasminogen activator inhibitor-1, and factor VIII activity). We also
      evaluated the clinical applicability of these hemostatic factors by examining
      whether AF subjects with established clinical or echocardiographic predictors of
      thromboembolism had higher levels of these factors. METHODS AND RESULTS: Of the
      3,212 participants of a Chinese population-based study, 53 subjects (1.7%) with
      AF were identified. Among the hemostatic factors measured, t-PA antigen (median
      12.8 vs 8.1 ng/mL; P < 0.01) and factor VIII activity (median 155% vs 133%; P <
      0.05) were significantly higher in AF subjects after adjustment for age and sex.
      In multivariate analysis, features independently associated with t-PA antigen
      levels were AF, sex, body mass index, systolic blood pressure, total cholesterol,
      triglycerides, and left ventricular systolic dysfunction. Features independently
      associated with factor VIII activity levels included AF, age, and total
      cholesterol. Levels of both t-PA antigen and factor VIII activity were primarily
      elevated in AF subjects with predictors of thromboembolism (age > 75 years,
      hypertension, diabetes, and left ventricular systolic dysfunction), whereas in AF
      subjects with no thromboembolic predictors, plasma levels of hemostatic factors
      examined were similar to those without AF. CONCLUSION: We demonstrated that
      nonvalvular AF was independently associated with increased peripheral levels of t
      PA antigen and factor VIII activity. Levels of both hemostatic factors were
      primarily elevated in AF subjects with predictors of thromboembolism. Whether
      these hemostatic factors are independently predictive of future thromboembolic
      events in AF patients requires further investigation.

PMID- 11523533
TI  - Heavy drinking from the freshman year into early young adulthood: the roles of
      stress, tension-reduction drinking motives, gender and personality.
AB  - OBJECTIVE: This study investigated the relationship between stress (defined
      alternatively as negative life events and emotional distress) and heavy drinking
      across late adolescence and early young adulthood, as well as the roles of
      tension-reduction drinking motives and gender as moderators of that relationship.
      The role of personality variables (neuroticism, behavioral undercontrol and
      extraversion) as moderators also was explored. METHOD: The data were obtained
      from 485 individuals (255 women) participating in a five-wave longitudinal study
      that spanned 7 years. The effects on heavy drinking of stress (either negative
      life events or emotional distress), tension-reduction drinking motives, gender
      and personality were analyzed each year with hierarchical multiple regression.
      RESULTS: Stress (negative life events) was positively related to heavy drinking,
      but only for men with stronger tension-reduction drinking motives at Year 4 (age
      21). The relationship between tension-reduction drinking motives and heavy
      drinking was positive, developmentally graded, and moderated by gender, after the
      freshman year, the role of tension-reduction drinking motives in heavy drinking
      became less important for women, relative to men, a trend that grew stronger
      after the college years. Behavioral undercontrol played a limited role in the
      relationship of gender and tension-reduction drinking motives to heavy drinking.
      CONCLUSIONS: The findings have implications for theories of stress-related and
      stress-motivated drinking. Such theories should consider developmental processes,
      particularly the transition to adult drinking status at age 21 and the roles of
      tension-reduction drinking motives, gender and behavioral undercontrol.

PMID- 11523534
TI  - Bibliography. Current world literature. Corneal and conjunctival disorders.

PMID- 11523535
TI  - Atmospheric volatile organic compound measurements during the 1996 Paso del Norte
      Ozone Study.
AB  - Ambient air VOC samples were collected at surface air quality monitoring sites,
      near sources of interest, and aloft on the US (El Paso) and Mexican (Ciudad
      Juarez) side of the border during a six-week period of the 1996 Paso del Norte
      Ozone Study. Samples were collected at five sites, three on the US side and two
      on the Mexican side, during nine intensive operation days when high ozone levels
      were forecast for the area. Six other sites were sampled to characterize up-wind,
      down-wind and other emission sources. Samples for determining source profiles
      were collected for rush hour traffic, propane-powered bus exhaust, automobile
      paint shop emissions, propane fuels, and industrial manufacturing in Cd. Juarez
      and a refinery in El Paso. Most samples were collected in electro-polished
      stainless steel canisters for determination of C2 to C(10+) hydrocarbons by GC
      FID. Carbonyl samples were collected on DNPH impregnated cartridges at three
      surface sites during aircraft flights and analyzed by HPLC. This paper presents
      the spatial and temporal characteristics of VOC species concentrations and
      compositions to examine the differences and similarities of the various locations
      and time periods. Overall surface, total non-methane hydrocarbon values ranged
      from 0.1 to 3.4 ppmC with the highest concentrations being recorded in the
      morning and evening at five vehicle-dominated sites, three in Cd. Juarez and two
      in El Paso. Toluene in El Paso samples and propane, which is used as a cooking
      and transportation fuel in Cd. Juarez, were the most abundant hydrocarbons. The
      most abundant carbonyls were acetaldehyde, acetone and formaldehyde.

PMID- 11523536
TI  - [Alzheimer dementia--a disorder of lipoprotein metabolism?].

PMID- 11523537
TI  - [Historic evolution of physicians' reimbursement].

PMID- 11523539
TI  - Epstein-Barr virus (EBV) and human disease: facts, opinions and problems.
AB  - The human herpesvirus, Epstein-Barr virus (EBV), has classically been associated
      with two pathologies with frequencies approaching 100%. One of these, Burkitt's
      lymphoma (BL), is of B-cell origin and the other, nasopharyngeal carcinoma (NPC),
      is a tumour of poorly differentiated epithelial cells. More recently, EBV had
      been identified with frequencies from a few percent to 100% (in one case) with a
      variety of other malignancies. These include Hodgkin's disease (HD; where in the
      west, the frequency of association is about 50%), sino-nasal T-cell lymphomas,
      lymphoepitheliomas, some sarcomas and breast cancers, other cancers from the head
      and neck, and lymphomas arising in patients with immune dysfunctions. Since EBV
      is ubiquitous, with the vast majority of the world's population having met and
      seroconverted to the virus, the diversity of tumours with which it has now been
      associated represents a substantial health burden. In a recent IARC monograph,
      EBV was classified as a group 1 carcinogen. Here, the data on BL and NPC, as they
      relate to geographical restrictions, viral strain variation, co-factors in
      disease, and genetic components are reexamined. We raise the question whether in
      their origins, these tumours genuinely reflect distinct and independent events,
      as deemed at present, or may represent a response by different cell types to
      common extracellular factors. For example, a situation in Kenya apparently
      existed in the past, where both BL and NPC were observed in ethnic Africans with
      roughly equal frequencies; more recently, in Kenya, EBV has been identified in
      nearly 100% of the tumours in children with HD. We also consider tumours where
      the viral association is reportedly of low frequency, and offer explanations for
      these data, including the possibility of loss of the viral genome once malignancy
      has been initiated. If this phenomenon occurs as a frequent secondary event, EBV
      could be an even greater health risk than presently believed.

PMID- 11523540
TI  - Special issue in honor of Ruggero Montesano.

PMID- 11523541
TI  - The identification of human carcinogens and primary prevention of cancer.
AB  - Primary prevention is based on the incontrovertible logic that a most efficient
      way to decrease the risk for a disease is to avoid, or reduce to minimal
      attainable levels, exposures to agents that can cause the disease or contribute
      to an increase in risk for the disease. This notwithstanding, the adoption of
      primary prevention measures has often encountered serious obstacles and
      unjustifiable delays. The success of primary prevention has also been limited by
      the combined effect of: (a) the inefficient and/or incomplete use of the
      cumulated etiological knowledge: (b) the spectrum of target organs for human
      carcinogens which does not include some of the most common cancer sites, a
      limitation that may be related to a disregard of epidemiological results and case
      reports that provide evidence that is less than sufficient of a causal
      relationship between an exposure and human cancer: (c) the pressure that powerful
      economic interests may have exerted in a variegated way to interfere or delay
      implementation of preventive measures that could have decreased their profit, and
      (d) the decreased acceptance of the ability of experimental results to predict
      similar effects in humans, in spite of the evidence that positive carcinogenicity
      results in experimental animals have often preceded and could indeed have
      predicted similar results in humans.

PMID- 11523538
TI  - IL-5 induces proliferation and activation of microglia via an unknown receptor.
AB  - While the effects of interleukin-3 (IL-3) and granulocyte macrophage-colony
      stimulating factor (GM-CSF) on microglia are well documented, very little is
      known about the effects of a related cytokine, interleukin-5 (IL-5). We therefore
      undertook studies to determine how IL-5 alters various aspects of microglial
      functioning. Treatment of microglia with IL-5 resulted in the induction of
      proliferation at levels similar to those induced by GM-CSF. IL-5 also increased
      cellular metabolism of microglial cells. To determine whether increased
      metabolism correlated with activation of microglia, we measured levels of
      nitrite, a breakdown product of nitric oxide. Treatment of microglial cultures
      with IL-5 increased nitrite levels, while GM-CSF treatment had no effect.
      Treatment of microglia with IL-5 did not cause activation of the signal
      transduction pathways linked to the classical IL-5 receptor, STAT5A/5B and ERK1
      and ERK2. It is therefore likely that the effects of IL-5 on microglia are not
      mediated via the classical IL-5 receptor, but rather via a novel receptor.

PMID- 11523542
TI  - The interface between molecular biology and cancer research.
AB  - During the last thirty years, cancer research has been a remarkably fruitful
      resource for molecular biologists. Numerous fundamental discoveries in basic
      biology have come out of research into the properties of cancer cells; for
      example, the discovery of reverse transcriptase, RNA splicing and the protein
      kinases. Recently, information has started to flow in the other direction, and we
      are at last beginning to see molecular biology yielding discoveries of practical
      importance in the management and control of human cancer. Some of the past and
      possible future interactions of molecular biology and cancer research are
      discussed in this paper.

PMID- 11523543
TI  - Three steroidal alkaloids from Buxus microphylla.
AB  - Three new steroidal alkaloids have been isolated from the leaves and stems of
      Buxus microphylla Sieb et Zucc. They are buxmicrophylline B, C and D. Their
      structures were elucidated by extensive analysis of the spectral data.

PMID- 11523544
TI  - A new cardenolide uzarigenen-3-O-beta-D-xylopyranosyl (1-->2)-alpha-L
      rhamnopyranoside.
AB  - A new cardenolide C34H52O12, m.p. 225-226 degrees C, [M+ -H] 651 (EIMS) was
      isolated from the acetone soluble fraction of the concentrated 90% ethanolic
      extracts of the seeds of Tamarindus indica (Linn.). It was identified as
      uzarigenin-3-O-beta-D-xylopyranosyl (1 -->2)- alpha-L-rhamnopyranoside (I) by
      different colour reactions, chemical degradations and spectral analysis.

PMID- 11523545
TI  - Structures of two new diterpenoid dimers from bulbs of Fritillaria ebeiensis.
AB  - Two new ent-kauranoid diterpenoid dimers, fritillebin C (1) and fritillebin D
      (2), were isolated from the bulbs of Fritillaria ebeiensis G.D. Yu and G.Q. Ji.
      Their structures were determined to be ent-16beta-hydroxy-kauran-17-yl ent
      16beta3-kauran-17-oate (1); ent-16alpha-hydroxy-kauran-17-yl ent-16beta-kauran-17
      oate (2) by means of spectral analysis and chemical evidence.

PMID- 11523546
TI  - Structure elucidation of glycan of glycoconjugate LbGp3 isolated from the fruit
      of Lycium barbarum L.
AB  - The structure of the repeat unit of the glycan of glycoconjugate LbGp3 with
      pronounced immunoactivity, isolated from the fruit of Lycium barbarum L. was
      elucidated based on methylation analysis, partial acid hydrolysis and 1H, 13C NMR
      spectroscopy of the original glycan and products of its partial hydrolysis.

PMID- 11523547
TI  - A triterpene from Ficus pumila.
AB  - The leaves of Ficus pumila afforded a new neohopane (1) by silica gel
      chromatography. The structure of 1 was elucidated by 1D and 2D NMR and IR
      spectroscopy and mass spectrometry. It showed antimicrobial activity against
      Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis and Candida albicans
      with an average antimicrobial index of 0.5, 0.3, 0.3 and 0.7, respectively, at a
      concentration of 30 microg.

PMID- 11523548
TI  - Chemical constituents of Isodon melissoides.
AB  - Four new diterpenoids, melissoidesin E (1), F (2), G (4) and H (5), together with
      one known diterpenoid and two lignan glycosides, were isolated from aerial parts
      of Isodon melissoides. Their structures were established by spectral analysis and
      comparison with related compounds. The lignan glycosides (compounds 7 and 8) were
      the first examples to be isolated from the genus Isodon plants.

PMID- 11523549
TI  - Effects of genistein, a soybean-derived isoflavone, on proliferation and
      differentiation of B16-BL6 mouse melanoma cells.
AB  - Genistein, a soybean-derived isoflavone, may contribute to the lower cancer
      incidence in South Asian countries. In this study, the effects and molecular
      mechanisms of genistein on growth and differentiation of B16-BL6 mouse melanoma
      cells were investigated. Genistein suppressed the growth of these melanoma cells.
      The IC50 value is 15.5 microM. On the other hand, genistein induced the changes
      of cell shape and cytoskeletal network. The cytoskeletal filaments were induced
      to form a bundle along the direction of elongation of the cells. Moreover,
      tyrosine phosphorylation levels of cytoskeleton-associated proteins decreased
      after the cells were exposed to 20 or 30 microM of genistein for 3 days. All
      these morphological and molecular changes were accompanied by appearance of the
      differentiated phenotypes. Genistein induced the increase of cellular melanin
      content, enhancement of tyrosinase activity, and decrease of colonization
      potentials in soft agar in a time-dependent and dose-dependent manner. The
      effective concentration was no more than 10 microM after 3 days' exposure. The
      tumorigenic potentials of B16-BL6 cells in C57BL/6 mouse also decreased after
      exposure to 20 or 30 microM of genistein for 3 days. When expressions of tumor
      related genes were investigated in the differentiation-induced cells, the content
      of P53 dramatically increased while that of c-Myc protein decreased. Therefore,
      due to its ability to induce cellular and molecular changes, genistein suppressed
      the growth and induced differentiated phenotypes in B16-BL6 melanoma cells.

PMID- 11523550
TI  - Flavonoid glycosides from Thalictrum przewalskii.
AB  - A new flavonoid glycoside, 5,7-dihydroxy-4'-methoxyflavone-7-O-[6-O-(4-O-acetyl
      alpha-L-rhamnosyl)-3-O-beta-D-glucosyl]-6-O-acetyl-beta-D-glucoside and three
      known flavonoid glycosides, 5,7-dihydroxy-4-methoxyflavone-7-0-[6-0-(4-0-acetyl
      alpha-L-rhamnosyl)]-beta-D-glucoside, 3,5,7, 4'-tetrahydroxyflavonol-3-O-beta-D
      glucoside and 5,7-dihydroxy-4'-methoxyflavone-7-O-(6-O-alphaL-rhamnosyl)-beta-D
      glucoside were isolated from the whole plant of Thalictrum przewalskii. Their
      structures were determined on the basis of spectroscopic evidences.

PMID- 11523551
TI  - Evaluation of toxicity of some saponins on brine shrimp.
AB  - Toxicity of several types of saponins (1-11) against brine shrimp (Artemia
      salina) were evaluated. As a result, it was found that most tested compounds were
      not toxic to brine shrimp at high enough concentration. The most toxic saponin
      (1) to brine shrimp showed also cytotoxicity towards HL-60 tumor cell line using
      MTT assay. Brine shrimp model may thus be used as bench-top assay in finding
      cytotoxic components from saponin-containing fractions of plant extracts.

PMID- 11523552
TI  - A triterpenoid saponin from Albizia julibrissin.
AB  - A triterpenoid saponin (1) was obtained from the stem barks of Albizia
      julibrissin Durazz. Its structure was elucidated as 3-O-[beta-D-xylopyranosyl-(1 
      -> 2)-alpha-L-arabinopyranosyl-(1 --> 6)-beta-D-glucopyranosyl]-21-O-[(6S)-2
      trans-2-hydroxymethyl-6-methyl-6-O-beta-D-quinovopyranosyl-2, 7-octadienoyl]-16
      deoxy-acacic acid 28-O-beta-D-glucopyranosyl-(1 --> 3)-[alpha-L-arabinofuranosyl
      (1 --> 4)]-alpha-L-rhamnopyranosyl-(1 --> 2)-beta-D-glucopyranosyl ester (1),
      named as Julibroside J26, based on the chemical and spectral methods.

PMID- 11523553
TI  - Three new diterpenoids from Mallotus apelta Muell.Arg.
AB  - Three new diterpenoids, 10-hydroxy-cembrene-5-one, 6-hydroxy-cembrene-5,10-dione
      and 2alpha,4beta,15,16-tetrahydroxyl-dolabradane were isolated from the petroleum
      ether fraction of the alcoholic extract of Mallotus apelta Muell.Arg. Their
      structures were determined by spectral methods.

PMID- 11523554
TI  - Two new caffeyol glycosides from Forsythia suspensa.
AB  - Two new caffeoyl glycosides of phenethyl alcohol, suspensaside A (1) and
      suspensaside B (2), were isolated from the fruits of Forsythia suspensa. Also
      obtained in this investigation were two known compounds forsythiaside (3) and
      suspensaside (4). The structures of compounds 1 and 2 were established by ID and
      2D NMR techniques and chemical methods.

PMID- 11523555
TI  - Two dichromenes from Evodia lepta.
AB  - Two new dichromenes, dichromene C and dichromene D, were isolated from the aerial
      parts of Evodia lepta. Their structures were determined by spectroscopic
      analysis.

PMID- 11523556
TI  - Structure-activity relationships of ketolides vs. macrolides.
AB  - Since their discovery, the macrolide antimicrobials have proved clinically
      valuable for the treatment of respiratory tract infections, offering coverage
      against a broad spectrum of pathogens and excellent tolerability. However, the
      global increase in macrolide resistance among respiratory pathogens, particularly
      Streptococcus pneumoniae, threatens their future usefulness. The ketolides, of
      which telithromycin is the first to reach clinical development, represent a new
      generation of antimicrobials that have been developed with a view to overcoming
      the problem of macrolide resistance. Telithromycin is structurally derived from
      macrolides, and possesses several distinguishing features that are important for
      its improved microbiological profile. The L-cladinose at position C3 of the
      miacrolactone ring has been replaced with a keto function. This modification
      enables telithromycin to bind to its target without tripping the inducible
      resistance to macrolide-lincosamide-streptograminB (MLS(B)) drugs that many
      groups of pathogens exhibit. The C6 position has been modified by the addition of
      a methoxy group. This helps prevent hemiketalization of the C6 position with the
      3- and 9-keto groups, thereby conferring excellent acid stability, particularly
      at gastric pH values. Telithromycin is differentiated from other ketolide
      compounds by the addition of a large aromatic N-substituted carbamate extension
      from positions C11/C12. This carbamate extension improves binding of the drug to
      its target, the 50S ribosomal subunit, as demonstrated in in vitro experiments.
      Telithromycin binds to wild-type ribosomes with 10-fold greater affinity than
      erythromycin A and 6-fold greater affinity than clarithromycin; its affinity for
      MLS(B)-resistant ribosomes is > 20 times that of both macrolides. The increased
      ribosomal affinity of telithromycin correlates with its superior potency against
      Gram-positive cocci both in vitro and in vivo, and is one of the factors
      determining the drug's activity against MLS(B)-resistant respiratory pathogens.

PMID- 11523557
TI  - Safeguarding future antimicrobial options: strategies to minimize resistance.
AB  - Current antimicrobial therapy for community-acquired respiratory tract infections
      (RTIs) is empirical and is influenced by local differences in etiology and
      bacterial susceptibility. As the rates of resistance and cross-resistance to
      currently available classes of antimicrobial agents increase, their effectiveness
      becomes compromised. These issues demand improved strategies for antimicrobial
      usage, and the development of new agents that do not select resistance are
      essential to safeguard future antimicrobial efficacy. Strategies to minimize
      antimicrobial resistance among common RTIs include reducing antimicrobial
      consumption and controlling the development and spread of resistance through
      appropriate prescribing and the use of short-duration, once-daily treatments to
      improve patient compliance. Importantly, the ketolides, which are a new family of
      antimicrobials, have been recently developed specifically for the treatment of
      community-acquired RTIs. The first member of this new family, telithromycin, has
      been shown to have potent activity against common and atypical respiratory
      pathogens, including beta-lactam- and macrolide-resistant strains, and has a low
      potential to select for or induce cross-resistance. These properties, combined
      with its good tolerability across patient groups, make telithromycin an
      attractive option for the first-line empiric treatment of RTIs with the potential
      to limit the future development of resistance.

PMID- 11523558
TI  - Microbiological profile of telithromycin, the first ketolide antimicrobial.
AB  - Telithromycin, the first of the ketolide antimicrobials, has been specifically
      designed to provide potent activity against common and atypical/intracellular or
      cell-associated respiratory pathogens, including those that are resistant to beta
      lactams and/or macrolide-lincosamide-streptograminB (MLS(B)) antimicrobials.
      Against gram-positive cocci, telithromycin possesses more potent activity in
      vitro and in vivo than the macrolides clarithromycin and azithromycin. It retains
      its activity against erm-(MLS(B)) or mef-mediated macrolide-resistant
      Streptococcus pneumoniae and Streptococcus pyogenes and against Staphylococcus
      aureus resistant to macrolides through inducible MLS(B) mechanisms. Telithromycin
      also possesses high activity against the Gram-negative pathogens Haemophilus
      influenzae and Moraxella catarrhalis, regardless of beta-lactamase production. In
      vitro, it shows similar activity to azithromycin against H. influenzae, while in
      vivo its activity against H. influenzae is higher than that of azithromycin.
      Telithromycin's spectrum of activity also extends to the atypical, intracellular
      and cell-associated pathogens Legionella pneumophila, Mycoplasma pneumoniae and
      Chlamydia pneumoniae. In vitro, telithromycin does not induce MLS(B) resistance
      and it shows low potential to select for resistance or cross-resistance to other
      antimicrobials. These characteristics indicate that telithromycin will have an
      important clinical role in the empirical treatment of community-acquired
      respiratory tract infections.

PMID- 11523559
TI  - Pharmacodynamic and pharmacokinetic considerations in antimicrobial selection:
      focus on telithromycin.
AB  - The effectiveness of empirical treatment for respiratory tract infections (RTIs)
      with commonly available antimicrobials is threatened by the development of
      microbial resistance and cross-resistance between treatments. Pharmacokinetic and
      pharmacodynamic profiling of antimicrobial agents is increasingly being used to
      select the most appropriate treatment and dosage schedules for RTIs. In addition
      to enhancing management strategies with existing treatments, these profiles have
      played a key part in identifying dosage schedules for a new family of
      semisynthetic antimicrobials, the ketolides. The first member of this family,
      telithromycin, has potent activity against both common and atypical pathogens
      involved in RTIs and does not induce resistance to the macrolide-lincosamide
      streptogramin B (MLS(B)) antimicrobials in vitro. Its pharmacokinetic profile
      reveals that telithromycin can be administered once daily without regard for
      meals, requires no dose reduction in elderly patients or those with hepatic
      impairment, and penetrates rapidly into respiratory tissues and fluids, a feature
      probably related to its ability to concentrate inside white blood cells.
      Pharmacodynamic studies indicate that the area under the concentration-time curve
      (AUC):minimum inhibitory concentration (MIC) and the peak plasma concentration
      (Cmax):MIC ratios are important determinants of bacteriological outcome with
      telithromycin. Telithromycin has a high AUC:MIC ratio compared with macrolide
      antimicrobials, which is expected to result in enhanced antimicrobial activity.
      These properties of telithromycin, combined with its good tolerability and low
      propensity for drug interactions, provide the basis for potent and reliable
      treatment of RTIs with a convenient, once-daily regimen.

PMID- 11523560
TI  - Community-acquired pneumonia: the evolving challenge.
AB  - Community-acquired pneumonia (CAP) is a common disorder that has been the focus
      of a major international research effort to define its epidemiology, etiology and
      management. The microbial etiology of CAP is complex and severity assessment is
      important in identifying at-risk populations as well as defining therapeutic
      strategies. Laboratory investigations rarely influence initial therapy, which
      remains empirical. Guidelines have been developed in many countries in response
      to the need to optimize management and outcomes. However, many of these
      guidelines have been based on expert opinion rather than robust evidence. New
      evidence-based guidelines have been developed that take into account disease
      severity, the local distribution of pathogens and their likely susceptibility to
      antimicrobials, and that include newer treatment options. Macrolide and
      fluoroquinolone antimicrobials feature heavily in these new treatment
      recommendations. Promising new therapies continue to emerge that may offer
      advantages over fluoroquinolones and macrolides, in particular with regard to the
      problem of resistance. Of these, the ketolides are of special interest.
      Telithromycin, the first ketolide antibacterial, has been evaluated in the
      treatment of > 700 patients with CAP. A once-daily oral dose of telithromycin 800
      mg for 7-10 days produces clinical and bacteriological success rates > 90% and
      equivalent to standard comparator agents, whilst maintaining efficacy against
      resistant pathogens.

PMID- 11523561
TI  - Hereditary neuralgic amyotrophy.
AB  - Hereditary neuralgic amyotrophy (HNA) belongs to the group of recurrent focal
      neuropathies, the other major representative being hereditary neuropathy with
      liability to pressure palsies. The search for the HNA gene has now focused on a
      locus on chromosome 17q24-q25. Most HNA families show linkage to this locus, but
      recent evidence indicates that HNA is genetically heterogeneous. Detailed
      analysis of these unlinked families has broadened our perception of the HNA
      phenotype, and currently two different clinical courses can be discerned: the
      classical relapsing-remitting course and a chronic undulating course. After 5
      years of molecular genetic research, this disease remains enigmatic. At present,
      we can only speculate how such very diverse stimuli as immunizations, childbirth,
      infections, strenuous exercise, and immobilization can trigger painful attacks of
      brachial plexus palsies in genetically susceptible individuals.

PMID- 11523562
TI  - Leber hereditary optic neuropathy: clinical and molecular genetic findings.
AB  - Leber hereditary optic neuropathy (LHON) is a maternally inherited disease
      characterized by acute or subacute painless central visual loss usually in young
      adults, predominantly in males. Except for optic atrophy, LHON patients are
      usually otherwise healthy. Occasionally, LHON is associated with neurological,
      cardiac, and skeletal changes. The clinical course of LHON has several stages.
      Peripapillary microangiopathy is present from the beginning. Microangiopathy
      disappears as the disease progresses towards the end stages. Simultaneously, the
      retinal nerve fiber layer fades from view, first papillomacular nerve fiber
      bundles, and months later, the whole nerve fiber layer becomes atrophic. At the
      end stage the centrocecal scotoma is large and absolute. Loss of vision is
      usually permanent, but spontaneous recovery can occur. Despite a few attempts, no
      effective treatment to prevent or halt LHON has been found. Several mitochondrial
      DNA (mtDNA) mutations are associated with LHON, but the pathogenic processes
      leading to optic nerve atrophy are largely unknown. About 15% of the families are
      heteroplasmic, i.e., both mutant and wild type mtDNA coexist within an
      individual. The level of heteroplasmy between different tissues can vary
      markedly. mtDNA mutations are not sufficient to cause visual loss in LHON, since
      not all individuals harboring a pathogenic LHON mutation express the disease.
      There are additional genetic and/or environmental precipitating factors, but thus
      far they are unknown.

PMID- 11523563
TI  - Mapping of the second Friedreich's ataxia (FRDA2) locus to chromosome 9p23-p11:
      evidence for further locus heterogeneity.
AB  - Friedreich's ataxia (FRDA), the most-common form of autosomal recessive ataxia,
      is inherited in most cases by a large expansion of a GAA triplet repeat in the
      first intron of the frataxin (X25) gene. Genetic heterogeneity in FRDA has been
      previously reported in typical FRDA families that do not link to the FRDA locus
      on chromosome 9q13. We report localization of a second FRDA locus (FRDA2) to
      chromosome 9p23-9p11, and we provide evidence for further genetic heterogeneity
      of the disease, in a family with the classic FRDA phenotype.

PMID- 11523564
TI  - Novel mutation in the TOR1A (DYT1) gene in atypical early onset dystonia and
      polymorphisms in dystonia and early onset parkinsonism.
AB  - Dystonia is a movement disorder involving sustained muscle contractions and
      abnormal posturing with a strong hereditary predisposition and without a distinct
      neuropathology. In this study the TOR1A (DYT1) gene was screened for mutations in
      cases of early onset dystonia and early onset parkinsonism (EOP), which
      frequently presents with dystonic symptoms. In a screen of 40 patients, we
      identified three variations, none of which occurred in EOP patients. Two
      infrequent intronic single base pair (bp) changes of unknown consequences were
      found in a dystonia patient and the mother of an EOP patient. An 18-bp deletion
      (Phe323_Tyr328del) in the TOR1A gene was found in a patient with early onset
      dystonia and myoclonic features. This deletion would remove 6 amino acids close
      to the carboxy terminus, including a putative phosphorylation site of torsinA.
      This 18-bp deletion is the first additional mutation, beyond the GAG-deletion
      (Glu302/303del), to be found in the TOR1A gene, and is associated with a distinct
      type of early onset dystonia.

PMID- 11523565
TI  - Genetic susceptibility to MS: a second stage analysis in Canadian MS families.
AB  - Four published genome screens have identified a number of markers with increased
      sharing in multiple sclerosis (MS) families, although none has reached
      statistical significance. One hundred and five markers previously identified as
      showing increased sharing in Canadian, British, Finnish, and American genome
      screens were genotyped in 219 sibling pairs ascertained from the database of the
      Canadian Collaborative Project on Genetic Susceptibility to MS (CCPGSMS). No
      markers examined met criteria for significant linkage. Markers located at 5p14
      and 17q22 were analyzed in a total of 333 sibling pairs and attained mlod scores
      of 2.27 and 1.14, respectively. The known HLA Class II DRB1 association with MS
      was confirmed (P<0.0001). Significant transmission disequilibrium was also
      observed for D17S789 at 17q22 (P=0.0015). This study highlights the difficulty of
      searching for genes with only mild-to-moderate effects on susceptibility,
      although large effects of specific loci may still be present in individual
      families. Future progress in the genetics of this complex trait may be helped by
      (1) focussing on more ethnically homogeneous samples, (2) using an increased
      number of MS families, and (3) using transmission disequilibrium analysis in
      candidate regions rather than the affected relative pair linkage analysis.

PMID- 11523566
TI  - EGR2 mutation R359W causes a spectrum of Dejerine-Sottas neuropathy.
AB  - Heterozygous mutations in the early growth response gene 2 (EGR2), which encodes
      a zinc-finger transcription factor that regulates the late stages of myelination,
      cause myelinopathies including congenital hypomyelinating neuropathy, Dejerine
      Sottas neuropathy (DSN), and Charcot-Marie-Tooth disease type 1. We screened 170
      unrelated neuropathy patients without mutations involving the peripheral myelin
      protein 22 gene (PMP22), the myelin protein zero gene (MPZ), or the gap junction
      protein beta1 gene (GJB1) and identified two DSN patients with the heterozygous
      mutation R359W in the alpha-helix domain of the first zinc-finger of EGR2. We now
      report that this mutation is a recurrent cause of DSN, and that expressivity
      ranges from that typical for DSN to a more rapidly progressive neuropathy that
      can cause death by age 6 years. Furthermore, in contrast to patients with typical
      DSN, patients with the EGR2 R359W mutation have more respiratory compromise and
      cranial nerve involvement.

PMID- 11523567
TI  - Analysis of p53 mutation and expression in pleomorphic xanthoastrocytoma.
AB  - Pleomorphic xanthoastrocytoma (PXA) is a rare, superficially situated tumor that
      most frequently occurs in the temporal lobe of young adults and is often
      associated with seizures. It generally has a relatively favorable prognosis.
      Prior studies have shown that TP53 mutations may occur in up to 25% of PXAs,
      suggesting that PXA may have an etiology similar to diffuse astrocytoma rather
      than pilocytic astrocytoma. In the present study, we performed immunostaining for
      p53 protein and examined the mutation status of exons 5-8 of the p53 gene in 55
      PXAs, 8 of which had undergone one or multiple recurrences. Of 55 primary PXAs,
      35 (64%) showed staining in <1% of tumor cells, 15 (27%) in 1-10%, 4 (7%) in 11
      50%, and only 1 (2%) in >50%. No significant increase in p53 protein expression
      was noted in recurrences, even when associated with increased histological
      anaplasia. We found a TP53 heterozygous mutation in exon 7 in 1 of 47 primary
      tumors that yielded useable DNA, and in its recurrence 3 years later. This tumor,
      a grade II PXA, did not show signs of anaplastic transformation at recurrence.
      Eleven additional recurrences from 7 patients, 5 of which showed signs of
      histological anaplasia, did not show TP53 mutations in exons 5-8. Based on our
      data, the p53 mutation appears to be an uncommon (2%) genetic event in PXA
      formation and does not appear to be involved in tumor progression. Consequently,
      our findings suggest that the genetic events that underlie PXA formation differ
      from those involved in diffuse astrocytoma.

PMID- 11523568
TI  - Inter-laboratory comparison of DNA preservation in archival paraffin-embedded
      human brain tissue from participating centres on four continents.
AB  - DNA extracted from formalin-fixed and paraffin-embedded brain tissue is known to
      contain as yet ill-characterized inhibitors of the PCR process. As part of a
      project that aims to clarify the role of mitochondrial DNA sequence variation in
      human neurodegenerative diseases using DNA from various ethnic backgrounds, we
      have investigated factors that influence the preservation of archival DNA and its
      suitability for PCR. In this study, neuropathological tissue samples were
      analysed that had been routinely processed in 18 international centres on four
      continents. Following DNA extraction, PCR amplification of mitochondrial and
      nuclear DNA sequences was performed with and without additional purification of
      the template DNA. In addition, the DNA used for PCR was analysed by HPLC.
      Phosphate-buffered formalin proved to be a superior fixative compared with
      unbuffered aldehyde: DNA extraction resulted in greater yields, the molecular
      weight of the isolated DNA was higher and PCR was more successful. PCR inhibitors
      were identified as (1) high concentrations of small (<300 bp) DNA fragments that
      competitively compete with template DNA and (2) contaminants of the DNA template
      solution including denatured protein that cannot be completely removed by
      phenolic extraction. HPLC analysis did not reveal significant qualitative
      differences between DNA isolated from fresh-frozen tissue samples and DNA
      recovered from formalin-fixed, paraffin-embedded brain tissue. The fact that DNA
      could be amplified from the majority of tissue specimens in this study suggests
      that rare diseases and diseases where ethnic background plays an important role
      can be sampled for genetic polymorphism analysis on a global scale using archival
      neuropathological collections.

PMID- 11523569
TI  - An association between a subset of Finnish late-onset Alzheimer's disease and
      alpha2-macroglobulin.

PMID- 11523570
TI  - Information about occupational exposure to asbestos given to cases in an
      etiological study: ethical aspects.
AB  - The aim of the study is to consider some ethical aspects of the provision of
      information, to the cases or their families, about the assessment of occupational
      asbestos exposure obtained in a case-control study of malignant mesothelioma of
      the pleura. An informative letter with the result of the evaluation of their
      occupational exposure to asbestos was sent to the participating cases (and/or
      their family). Those whose exposure was classified as certain/probable were also
      informed of the legislation regarding occupational diseases. Of the 132 cases,
      32.6% of subjects and/or their families made telephone calls expressing interest
      in the content of the informative letter. Among the 63 cases classified as
      certain/probable exposure, this proportion was 47.6%. Out of 43 cases in which
      the age at diagnosis was < or = 65 years and the exposure to asbestos was
      certain/probable, only two (4.6%) were signed off work owing to occupational
      disease. Only one of the mesothelioma cases was recognized by the Spanish
      National Institute for Social Security (INSS) as having an occupational disease.
      The process of communication of the results of an epidemiological research should
      include the provision of information on the exposure data to each one of the
      subjects, and/or their families. There is a great disparity between the number of
      cases of certain/probable exposure to asbestos identified in our study, and the
      number registered as an occupational disease by the INSS.

PMID- 11523572
TI  - Classification methods for the identification of 'case' in epidemiological
      diagnosis of asthma.
AB  - The identification of the asthmatic 'case' in epidemiological research is a
      controversial issue. This study was aimed at classifying asthmatic subjects using
      a statistical decision rule that minimised the misclassification rate with
      respect to the clinicians' diagnosis. The rule was defined by a combination of
      predictors that are easily observed in epidemiological studies (asthma-like
      questions, physiological tests) without necessarily including the clinical
      opinion of expert physicians. From pooled data on 1103 subjects at the three
      Italian centres of the European Community Respiratory Health Survey (ECRHS) a
      post-consensus clinicians' diagnosis of asthma was obtained, and seven predictors
      were selected from among 18 potential candidates (specificity ranged from 64 to
      99%, but sensitivity ranged from 22 to 62%). This data set was processed with
      tree-structured classifier techniques (the Classification And Regression Trees,
      CART), classical discriminant analysis (Fisher's Linear Discriminant Function,
      LDF), and the neural network method (Multi-Layer Perceptron, MLP model). The
      results suggest that modifications of the 'classification tree' provide a more
      useful decision rule, sensitive (93%) and specific (85%), than either LDF or MLP.
      The decision tree is readily interpretable from a clinical perspective and uses
      five out of the seven predictors (in descending hierarchical order: ever had
      asthma, current asthma, shortness of breath, atopy and wheezing and breathless).
      The findings seem to indicate a considerable success with respect to previous
      epidemiological studies and await repetition in other ECHRS populations.

PMID- 11523571
TI  - Differences in trends of lung carcinoma by histology type in Israeli Jews and
      Arabs, 1981-1995.
AB  - Between 1981 and 1995 the national cancer register in Israel received reports on
      13,600 new cases of lung cancer. We evaluated the trends in total lung cancer and
      the histologic subtypes, in Jewish and Arab Israelis. During this period, the age
      adjusted incidence of lung cancer increased in the male Arab population, while
      for male Jews there was a non-significant decrease, for women in both population
      groups the rates were stable. When analyzed by age group, there was a significant
      decrease in incidence rates in Jewish males aged 75 years and older. An analysis
      by histologic subtypes showed two different trends. In the Jewish population, the
      age adjusted incidence rates of squamous cell carcinoma (SQCC) decreased and the
      incidence rates of adenocarcinoma (AC) increased, whereas in the Arab population
      the incidence rates of both subtypes increased, although statistically
      significantly only for SQCC. The changes found in the Jewish population are
      similar to those found in other western countries, where the rates of AC are
      increasing and the rates of SQCC are decreasing. The trends in the Arab
      population in Israel are different. This may be due to different trends in the
      prevalence of smoking in the two populations.

PMID- 11523573
TI  - Salmonella serotype Virchow causing salmonellosis in a Spanish region.
      Characterization and survey of clones by DNA fingerprinting, phage typing and
      antimicrobial resistance.
AB  - The diversity of Salmonella serotype Virchow organisms causing human
      salmonellosis in a Spanish region over 1990-1996 was studied by genetic and
      phenotypic procedures. Isolates showing identical DNA fingerprintings (ribotypes,
      RAPD-, REP- and ERIC-types) were clustered into the same lineage. Eight lineages
      were defined, of which only one caused diseases throughout the studied period.
      Eleven phage types (PTs) were represented, the most frequent being PTs 8, 19, 31,
      throughout the study period, and PT4a only during 1994. Class I integrons with
      variable regions of 1000-, 1600-, and 2300-bp in size were respectively present
      in 24, 3 and 5 multiresistant isolates; 43.5% of isolates were susceptible to
      antimicrobials, the rest were grouped into 17 R-profiles, including from one up
      to eight resistances. Plasmids could be recovered from 71.5% of isolates and
      grouped into 25 plasmid profiles (with 1-7 plasmids each); a 3.6 kb cryptic
      plasmid and a 60 kb virulence-plasmid were those most frequently found. Phage
      type, presence and size of integrons, and resistance profile were used to
      differentiate 39 clones. During the period studied 135 cases of Virchow
      salmonellosis were identified; 93 were apparently sporadic whereas the remainder
      were associated with four outbreaks. Infants under 1 year constituted the most
      frequent age group, with 30 gastroenteritis and two septicaemia episodes. In the
      four outbreaks, different clones falling into the prevalent lineage were
      implicated but each clone was involved in only one outbreak.

PMID- 11523575
TI  - Prevalence of hepatitis C infection among general practice patients in the Lyon
      area, France.
AB  - STUDY OBJECTIVE: To estimate the prevalence of hepatitis C virus (HCV) infection
      among patients in general practices. DESIGN AND PARTICIPANTS: A screening
      campaign requested by the French Health Insurance Fund and involving 271 general
      practitioners (GPs) and 96% of the 95 medical laboratories was conducted in the
      Lyon area. Each GP participated for one week and offered an HCV screening to all
      patients aged 18-69 years during this period. Risk factors were estimated by a
      medical questionnaire (MQ) filled in by the physician. MAIN RESULTS: From May to
      October 1997, 11,805 subjects were recruited into the study. Among them, 101 were
      known HCV positive. The MQ was filled up in 86% of the 11,704 remaining patients.
      Only 59% of those (6876/11,704) went to a laboratory to be tested. Fifty-one were
      ELISA positive of whom 30 were confirmed by RIBA or PCR. If we add 101 patients
      that were known HCV positive and estimate the prevalence among patients who did
      not go to the laboratory, this study gives a total estimated prevalence of 1.3%.
      CONCLUSIONS: The prevalence of HCV infection among patients of GPs is about 1.3%,
      very close to the estimate in the French general population. The substantial
      number of patients known HCV positive is probably related to the participation of
      GPs sensitised to HCV issues and who already have screened most of their HCV
      patients.

PMID- 11523574
TI  - High prevalence of HCV infection among the general population in a rural area of
      central Italy.
AB  - The hepatitis C virus infection (HCV) is the most frequent cause of hepatic
      infection in Europe. In Italy, anti-HCV positivity values are extremely variable,
      depending on the age and geographic location of the population being analysed.
      The aims of the study were: (1) evaluating positivity for anti-HCV antibodies in
      various age groups and determining the HBsAg in a mountainous and predominantly
      farming area in central Italy; (2) assessing some anamnestic and clinical
      variables through a questionnaire, submitted during the taking of blood samples,
      in order to determine HCV exposure and risk factors for the target population.
      344 subjects selected by random sampling among 3308 people, older than 16, were
      considered as the target population. A prevalence study was carried out. The
      sources of data were: blood samples taken to carry out the HCV positivity test; a
      questionnaire including items about exposures at risk and case-historical and
      clinical patient data. The risk of infection was evaluated by a multiple logistic
      regression model. The inferred HCV+ prevalence rate is 22.4/100 (95% confidence
      interval (CI): 20.8-24.1). An increasing age trend is shown with a higher
      positive predominance among females (28.99/100 vs. 14.29/100 in males). The
      positive HBsAg prevalence in the examined survey is 1.2/100. Variables associated
      with the HCV occurrence are case history of pneumonopathy (OR: 4.9) and exposure
      to parenteral therapies with glass syringes (OR: 3.3). This study is consistent
      with literature about the hypothesis of a north-south geographic gradient in the
      hepatitis C occurrence in Italy. Data clearly show the effects of the
      inappropriate use of medical or surgery practices on the population, with
      particular reference to the use of glass syringes. No elements prove that the
      farming features of the area may be predictive of HCV infection risk. The extent
      of the recorded prevalence values calls for the implementation of programmes
      aimed at detecting clusters or population areas at risk.

PMID- 11523576
TI  - High prevalence of Borrelia lusitaniae in Ixodes ricinus ticks in Tunisia.
AB  - To investigate whether ticks of the genus Ixodes are infected by Borrelia
      burgdorferi complex, 490 unfed Ixodes ricinus ticks were collected by flagging in
      three different areas of Tunisia in 1998. DNAs extracted from 81 adults, 60
      nymphs and 38 larvae were analysed after genic amplification of the non-coding
      spacer between the two copies of the rrl-rrf genes of B. burgdorferi sl. The
      prevalence of B. burgdorferi sl. in adults, nymphs and larvae was found to be 34,
      33.3 and 2.6%, respectively. All DNAs (n = 61) but one were identified as
      belonging to different genotypes of B. lusitaniae by analysis of the restriction
      fragment length polymorphism of amplification products. In addition, 290 adults,
      14 nymphs and 7 larvae were used to inoculate BSK-H medium to isolate
      spirochetes. Fifteen strains were isolated from adult ticks in the humid areas of
      Tunisia, whereas only one was obtained from larvae. Isolates were identified as
      B. lusitaniae (15/16) and B. garinii (1/16). These results provide new evidence
      for the existence of Lyme borreliosis in North Africa.

PMID- 11523577
TI  - Mortality of elderly subjects with self-reported asthma in a French cohort, 1991
      1996.
AB  - The objective of this study is to describe the mortality of subjects with self
      reported asthma aged 65 and over and to determine risk factors. PAQUID (Personnes
      Agees QUID) is a prospective cohort of 3777 elderly people, living at home in the
      South-west of France. The study of subjects with self-reported asthma started at
      3 year follow-up by using three epidemiological questions: 'Did you have an
      attack of wheezing that made you feel short of breath in the last 12 past
      months?', 'Have you ever had asthma?', 'Did you have at least one asthma attack
      in the previous 12 months?'. Data on mortality were available at 8-year follow
      up. Among the 2348 subjects who responded to these questions, 206 reported
      symptoms of asthma. Two groups were defined as 'pure asthma' and 'associated
      asthma' taking into account chronic bronchitis and smoking. Besides a gender
      difference, there was no statistical difference between those two groups so they
      were combined in a single group for further analysis. During the 5-year study
      period, 29.1% of subjects with self-reported asthma vs. 23.8% nonasthmatics died.
      A Cox model with delayed entry was used to calculate mortality rates. Interaction
      terms between each of the factors related to mortality and asthmatic status were
      analyzed to determine risk factors of mortality. Subjects with self-reported
      asthma had a higher risk of death than nonasthmatics (relative risk (RR): 1.49;
      95% confidence interval (CI) 1.1-1.9; p = 0.009). This risk was significant (RR:
      1.4; 95% CI: 1.05-1.8; p = 0.02) even after adjustment on morbidity variables.
      However no specific mortality risk factors were found for subjects with self
      reported asthma.

PMID- 11523578
TI  - The relation between self-rated health, socioeconomic status, body mass index and
      disability pension among middle-aged men.
AB  - The aim of this study was to assess the relations between self-rated health
      (SRH), socioeconomic status (SES), body mass index (BMI) and disability pension.
      Five birth-year cohorts of middle-aged male residents in Malmo, Sweden, were
      invited and 5313 with complete data constituted the cohort in this study. Each
      subject was followed for approximately 11 years. Of all subjects, 73% perceived
      their health as perfect and among obese men and blue collar workers, the
      corresponding figures were 67 and 68% respectively. The adjusted odds ratios for
      SRH less than perfect was 1.3 (CI: 1.1-1.7) for obese subjects and 1.7 (CI: 1.5
      1.9) for blue collar workers. The interaction between low SES and obesity was
      estimated to 11% which was not statistically significant. The adjusted relative
      risks (RR) of disability pension was 3.3 for subjects with SRH less than perfect,
      2.2 for blue collar workers and 2.0 for obese subjects, all statistically
      significant and only marginally less than the crude RR. Thus, SRH among middle
      aged men was associated with obesity as well as low SES, but no evidence of
      synergism between obesity and low SES in relation to SRH was found. Furthermore,
      poor SRH in particular, but also low SES and obesity, independently predicted
      disability pension.

PMID- 11523579
TI  - Trends in causes of death in the Aquitaine cohort of HIV-infected patients, 1995
      1997.
AB  - OBJECTIVE: To describe trends in the evolution of causes of death in a cohort of
      HIV-infected patients before and after the introduction of highly active
      antiretroviral treatment (HAART). METHODS: This descriptive study concerned all
      the patients of the Aquitaine cohort who died between 1995 and 1997. Causes of
      deaths were grouped into 13 'deaths due to an AIDS-defining underlying cause',
      and eight 'non AIDS' categories. Comparisons were performed between two
      comparable periods of 18 months, January 1995-June 1996 and July 1996-December
      1997 to focus on changes introduced by the prescription of HAART in June 1996.
      RESULTS: Five hundred and thirty-two deaths were notified in 36 months for a
      total of 3687 patients. The comparison between causes of deaths before and after
      June 1996 showed a significant difference between the two periods with a
      decreasing proportion of AIDS causes of death, from 82.7% to 72.2% (p = 0.007).
      CONCLUSION: HAART treatment has reduced the number and percentage of deaths due
      to AIDS-related causes among persons who died with HIV infection in South-western
      France.

PMID- 11523580
TI  - Occupational status and sleep-disordered breathing in a sample of French males.
AB  - Sleep-disordered breathing (SDB) and lower socio-professional status have in
      common a series of risk factors for ill health such as sedentary lifestyle,
      weight excess, heavy alcohol and tobacco consumption. We hypothesised that SDB
      will be more prevalent in lower socio-professional groups. A total of 496 male
      middle aged subjects (23-66 years) were tested with a protocol including a self
      completed structured sleep questionnaire (translation of the Madison sleep cohort
      study form), anthropometry (including neck, waist and hip girth) and a simple,
      non-invasive nose-throat examination by a specialist physician. The subjects were
      classified according to the 10 major groups of the ISCO-88 classification
      (International Labour Office). Our sampling base did not contain subjects in the
      major groups 1 (senior officials, legislators), 6 (fishery and agricultural
      workers), and zero (armed forces), thus these groups were not represented in the
      analysis. To improve the power of the statistical analysis, groups 3 and 4, 5 and
      7, 8 and 9 were merged, the analysis thus including four categories. The
      differences in demographic data were negligible; as expected, smoking was more
      prevalent in low socio-occupational groups (difference non-significant). A
      history of chronic bronchitis was more frequent in low socio-occupational groups,
      while a low physical job labour was more frequent in higher occupational groups.
      We did not find any differences in the prevalence of sleep-related respiratory
      disturbances (snoring, sleep apnoeas). This first study of the possible
      association between socio-occupational factors and sleep disordered breathing was
      negative, but we believe further studies, on larger samples, with a more
      homogeneous distribution of social groups are warranted.

PMID- 11523581
TI  - The distribution in specific IgE and the prevalence of allergic symptoms in 25-64
      years old inhabitants of an eastern and a western German city--results from
      Augsburg and Erfurt.
AB  - BACKGROUND: In an earlier study it has been found that allergic symptoms and
      sensitization in adults were more frequent in Hamburg (northern part of West
      Germany) compared to Erfurt (East Germany). The purpose of this study was to
      replicate these findings using data from Augsburg, a city from the southern part
      of West Germany. Furthermore the study population in this analysis was extended
      to higher age groups. METHODS: The prevalence of respiratory symptoms, assessed
      by a self-administered questionnaire, was compared in a random sample of adults,
      25-64 years of age, living in Augsburg (n = 1572) and Erfurt (n = 1648). From a
      subset (n = 754, resp. 1144) specific IgE to common aeroallergens were measured
      and atopic sensitization was defined as the presence of at least one positive
      specific IgE (CAP > 0). RESULTS: The prevalence of allergic rhinitis, wheezing,
      asthma and atopic sensitization was higher in Augsburg than in Erfurt (OR: 2.0;
      1.3; 2.1; 1.7; all p < 0.01). For these differences no specific explanation could
      be found, i.e. the percentage of sensitized persons was equally increased in
      Augsburg for asthmatics, patients with hay fever or asymptomatic subjects.
      Furthermore, sensitization was equally increased for all common allergens. The
      differences were largest for the youngest age group, but also existed for higher
      ages. CONCLUSIONS: The increased prevalence of allergies observed in Hamburg, a
      northern city of West Germany, is also found in Augsburg, a southern city of West
      Germany, both compared to Erfurt in East Germany. This supports the finding that
      unspecific causes related to western lifestyle play an important role. Further
      research is needed to identify the causal influences.

PMID- 11523582
TI  - Pulmonary tuberculosis and deprivation in hospitalised patients in Scotland.
AB  - During the last decades tuberculosis re-emerged in almost all over the world, in
      both developed and developing countries. Many risk factors were implicated to
      explain the re-emergences including the HIV epidemic. The aim of the study was to
      explore if tuberculosis is related with poverty in Scotland utilising routinely
      collected hospital discharge data for patients with pulmonary tuberculosis and
      postcode-derived Carstairs deprivation scores. The Carstairs and Morris index is
      composed of four indicators which were judged to represent material disadvantage
      in the population. A positive correlation was found between the cumulative
      incidence rate for hospitalised patients within each Health Board and the
      Carstairs deprivation score (r = 0.76, p < 0.01). A similar correlation was found
      between the cumulative incidence rate and the deprivation scores within each
      postcode sector (r = 0.47, p < 0.0001). These results supports findings by other
      researchers that poverty and tuberculosis are related, and might be one
      explanation for the recent re-emergence of tuberculosis.

PMID- 11523583
TI  - Risk factors for and relationship between bacterial vaginosis and cervicitis in a
      high risk population for cervicitis in Southern Iran.
AB  - In 1990, a study of the reproductive habits and cervical pathology in women of
      the Qashgha'i nomadic tribe, resulted in a high prevalence of cervicitis. This
      led us to explore the likely infectious agents responsible for a such high
      prevalence; to assess the difference in cervicitis rates between nomadic and non
      nomadic populations in the same area; and to determine the risk factors for and
      the relationship between cervicitis and bacterial vaginosis (BV). In 1996-1997 a
      study was carried out of 839 married women of the Qashgha'i, 274 of the Lor
      nomadic tribes, and 388 non-nomadic urban women. A gynaecological examination,
      Pap smear and vaginal secretion for assessing BV by gram staining were performed.
      Data was analysed by logistic regression. Backward stepwise regression was used
      to assess multivariable effects on risk of cervicitis. The prevalence of
      cervicitis was 88% in the Qashgha'i, 85% in the Lor and 71% in the urban
      population. In the multivariate backward stepwise regression analysis for
      predictors of cervicitis in the Qashgha'i, significant factors were decreased
      association with those over 40 (p < 0.004) and postpartum bleeding. In the Lor
      tribe the predictors were an increased risk after more than four pregnancies (p <
      0.01) and the use of contraception. Among the urban population, the risk of
      cervicitis was increased with the use of oral contraceptive previously (p < 0.03)
      or currently (p < 0.01). BV was strongly associated with cervicitis, with a
      relatively high attributable risk. Both sexual and childbirth exposures may be
      associated with cervicitis in these populations.

PMID- 11523584
TI  - Detection of Escherichia coli O157:H7 and other intestinal pathogens in patients
      with diarrhoeal disease.
AB  - Six hundred and six faeces specimens from patients with diarrhoea, aged 0->60 and
      living in the area of Fano (Italy), were examined for Escherichia coli O157:H7,
      Salmonella, Shigella and thermophilic Campylobacter spp. E. coli O157:H7 was not
      found, confirming the limited circulation of this bacterium in our country. On
      the other hand, Salmonellae were the most frequent pathogens (5.6%), followed by
      Campylobacters (2.3%) and Shigellae (0.3%).

PMID- 11523585
TI  - NRK-dependent phosphorylation of NAB-3: involvement in ACRK-13-mediated PUFFL
      activation or NEE-JRK activation of ACRO.

PMID- 11523586
TI  - Cloning of the ferrireductase that may be involved in iron transport in the small
      intestine: revisiting Crane's controversial oxidoreductase.

PMID- 11523587
TI  - The role of cerebral oedema in the pathogenesis of cerebral malaria.
AB  - It has been suggested that sequestration of parasitized red blood cells might
      contribute to the pathogenesis of cerebral malaria (CM), by hypoxia causing
      either: (i) compensatory vasodilatation with a resultant increase in the brain
      volume; or (ii) enhancing cytokine-induced nitric oxide (NO) production via
      induction of inducible NO synthase (iNOS). Available evidence suggests that
      cerebral oedema is the initiating and probably the most important factor in the
      pathogenesis of murine CM. The relevance of this model in the study of the
      pathogenesis of CM has been questioned. However, a closer look at published
      reports on both human and murine CM, in this review, suggests that the
      pathogenesis of the murine model of CM might reflect more closely the CM seen in
      African children than that seen in Asian adults. It is also proposed that the
      role of iNOS induction during CM is protective: that the primary purpose of iNOS
      induction is to inhibit the side effects of brain indoleamine 2,3-dioxygenase
      (IDO) induction and quinolinic acid accumulation during hypoxia.

PMID- 11523588
TI  - Vitamin E analogues as inducers of apoptosis: implications for their potential
      antineoplastic role.
AB  - Recent evidence suggests that vitamin E and its analogues, which have been used
      for many years as antioxidants, may not only protect cells from free radical
      damage but also induce apoptotic cell death in various cell types. While alpha
      tocopherol (alpha-TOH) is mainly known as an anti-apoptotic agent, its redox
      silent analogues either have no influence on cell survival (alpha-tocopheryl
      acetate, alpha-TOA), or induce apoptosis (alpha-tocopheryl succinate, alpha-TOS).
      Although precise mechanisms of apoptosis induction by alpha-TOS remain to be
      elucidated, there is evidence that this process involves both the
      antiproliferative and membrane destabilising activities of the agent. Alpha-TOS
      has been shown to induce apoptosis in malignant cell lines but not, in general,
      in normal cells, and to inhibit tumorigenesis in vivo. These features suggest
      that this semi-synthetic analogue of vitamin E could be a promising
      antineoplastic agent.

PMID- 11523589
TI  - Effect of the herbicide 4-CPA on human erythrocyte antioxidant enzymes in vitro.
AB  - To investigate the possible role of oxygen free radicals and oxidant stress in
      the toxic effects of phenoxyherbicides, we studied the in vitro effect of 4
      chlorophenoxyacetic acid (4-CPA) on various human erythrocyte antioxidant
      enzymes, namely glucose-6-phosphate dehydrogenase, catalase, selenium-dependent
      glutathione peroxidase, glutathione reductase and Cu/Zn-superoxide dismutase. 4
      CPA added in a dose of 1 ppm to human erythrocytes for 1 h caused a significant
      reduction in glucose-6-phosphate dehydrogenase (P <0.001) and catalase (P <0.001)
      activities, but did not significantly affect the activities of other enzymes.
      Such selective inactivation of specific erythrocyte antioxidant enzymes may play
      a role in the toxic effects of phenoxyherbicides.

PMID- 11523590
TI  - Influence of aging on Kupffer cell respiratory activity in relation to particle
      phagocytosis and oxidative stress parameters in mouse liver.
AB  - The influence of aging on the respiratory activity of stimulated Kupffer cells
      was investigated in the isolated perfused mouse liver in relation to colloidal
      carbon phagocytosis, and the content of glutathione (GSH) and protein carbonyls
      as parameters related to oxidative stress. Livers from aged (22 months) mice
      exhibited significant 35% and 65% decreases in the carbon uptake and in the
      carbon-induced O2 consumption compared to young (3 months) animals, respectively,
      with a concomitant 46% diminution in the carbon-induced O2 consumption/carbon
      uptake ratio. Hepatic GSH depletion was observed in aged mice compared to young
      animals, whereas protein oxidation was enhanced. It is concluded that aging leads
      to an impairment in the functional capacity of Kupffer cells reflected by a
      substantial reduction in their respiratory burst activity, lessened endocytic
      capacity and enhanced oxidative stress, that may contribute to increased
      susceptibility of the liver to noxious challenges.

PMID- 11523591
TI  - A comparative study by electron paramagnetic resonance of free radical species in
      the mainstream and sidestream smoke of cigarettes with conventional acetate
      filters and 'bio-filters'.
AB  - Tobacco smoking is the most important extrinsic cause, after the diet, for
      increasing morbidity and mortality in humans. Unless current tobacco smoking
      patterns in industrialised and non-industrialised countries change, cigarettes
      will kill prematurely 10 million people a year by 2025. Greece is at the top of
      the list of European countries in cigarette consumption. In 1997, a Greek tobacco
      company introduced a new 'bio-filter' (BF) claiming that it reduces substantially
      the risks of smoking. In a recent publication [Deliconstantinos G, Villiotou V,
      Stavrides J. Scavenging effects of hemoglobin and related heme containing
      compounds on nitric oxide, reactive oxidants and carcinogenic volatile
      nitrosocompounds of cigarette smoke. A new method for protection against the
      dangerous cigarette constituents. Anticancer Res 1994; 14: 2717-2726] it was
      claimed that the new 'bio-filter' (activated carbon impregnated with dry
      hemoglobin) reduces certain toxic substances and oxidants (like NO, CO, NOx,
      H2O2, aldehydes, trace elements and nitroso-compounds) in the gas-phase of the
      mainstream smoke. We have investigated by electron paramagnetic resonance (EPR)
      the mainstream and sidestream smoke of the BF cigarette, in comparison with three
      other cigarettes with similar tar and nicotine contents, that have conventional
      acetate filters. We found that BF cigarette smoke has similar tar radical species
      with the same intensity EPR signals to those of the other cigarettes. The ability
      of the aqueous cigarette tar extracts to produce hydroxyl radicals (HO*), which
      were spin trapped by DMPO, was very similar to, or even higher than, the other 3
      brands. The gas-phase of the mainstream smoke of the BF cigarette showed a 30-35%
      reduction in the production of oxygen-centered radicals (spin trapped with PBN).
      In the case of the sidestream smoke, BF cigarettes produced substantially higher
      concentrations of gas-phase radicals, compared to the other brands. These results
      suggest that BF is partially effective at removing some of the gas-phase oxidants
      but not effective in the reduction of tar and its radical species in the
      mainstream and sidestream smoke. It is well known from epidemiological studies
      that tar content is strongly associated with increasing risk to smokers of lung
      cancer. In our experiments, BF cigarettes produce a higher amount of tar and
      stable free radical species than the other 3 brands in the sidestream smoke
      (between puffs), thus potentially increasing risk to the smoker and passive
      smoker.

PMID- 11523592
TI  - The protective action of melatonin on indomethacin-induced gastric and testicular
      oxidative stress in rats.
AB  - Reactive oxygen species and lipid peroxidation play a role in the pathogenesis
      induced by the non-steroidal anti-inflammatory drug indomethacin. Melatonin (MLT)
      protection against indomethacin-induced oxidative tissue injury was investigated
      in gastric mucosa and testis of rats. MLT was administered intragastrically
      (i.g.) 30 min before the administration to fasted rats of 20 mg indomethacin/kg
      rat given i.g.. The area of gastric lesion as well as thiobarbituric acid
      reactive substances (TBARS) and lactate dehydrogenase (LDH) activity were found
      to be significantly increased 4 h after administration of indomethacin in rat
      gastric mucosa and testis indicating acute oxidative injury. MLT pretreatment
      reduced gastric lesion area to 80% of the indomethacin-treated rats and reduced
      the rise in TBARS concentration. MLT treatment reduced the LDH activity increase
      in testis but not in gastric mucosa. In indomethacin-treated rats, both the
      cytosolic Cu,Zn superoxide dismutase (Cu,Zn-SOD) and mitochondrial Mn-SOD
      activities were significantly diminished in gastric mucosa as well as the total
      SOD activity in testis. In addition, glutathione (GSH) content in both tissues
      was markedly decreased following indomethacin treatment. Pretreatment with MLT
      significantly ameliorated both the inhibition of SOD activity and the decreased
      GSH content in both tissues. Thus, these results show the effective
      antiperoxidative and preventive actions of MLT against indomethacin-induced
      gastric mucosal damage and testicular oxidative injury and we propose that this
      action might be relevant for its use with other free radical generating drugs.

PMID- 11523593
TI  - Intracellular redox status and antibiotic resistance in enterogastric micro
      aerophilic bacteria: evidence for the 'scavenging of oxygen' hypothesis.
AB  - Metronidazole and glutathione reduction activities were measured in situ in the
      micro-aerophilic bacteria Campylobacter coli and Helicobacter pylori employing
      14N- and 1H-nuclear magnetic resonance spectroscopy. The properties of these
      enzyme activities were investigated in matched pairs of strains with sensitive
      and resistant phenotypes to the antimicrobial metronidazole. The results
      indicated that the ability of each type of strain to reduce metronidazole
      corresponded to its sensitive or resistance phenotype. Higher levels of
      glutathione reduction and a significantly lower Ki for metronidazole were
      observed in sensitive strains compared to resistant strains. These findings
      suggested a relationship between the cellular machinery regulating intracellular
      redox status in C. coli and H. pylori, and the effects of metronidazole on these
      bacteria, which supported the 'scavenging of oxygen' hypothesis.

PMID- 11523594
TI  - Relative susceptibilities of mitochondrial and nuclear DNA to damage induced by
      hydrogen peroxide in two mouse germ cell lines.
AB  - The objective of this study was to determine the relative susceptibilities to the
      damaging effects of hydrogen peroxide of DNA in the mitochondrial and nuclear
      compartments of two murine germ cell lines. We used a quantitative polymerase
      chain reaction assay (QPCR) to measure gene- and mitochondrial-specific DNA
      damage and examined for the presence of alkali-labile sites using alkaline gel
      electrophoresis. No DNA damage was observed in a nuclear gene (beta-globin) in
      response to hydrogen peroxide treatment. In addition, no increase in alkali
      labile sites was observed. However, mitochondrial DNA suffered extensive damage
      which increased in a dose-dependent manner. These results demonstrate that the
      nuclear DNA in these germ cell lines is relatively resistant to peroxide-mediated
      DNA damage, and that mitochondrial DNA is a sensitive biomarker for oxidative
      stress in these cells.

PMID- 11523596
TI  - Inhibition of protein oxidation by the macrophage-synthesised antioxidant 7,8
      dihydroneopterin.

PMID- 11523595
TI  - Real time analysis of breath volatiles using SIFT-MS in cigarette smoking.
AB  - The selected ion flow tube mass spectrometry (SIFT-MS) technique enables real
      time analysis of trace volatiles at ppb levels without preconcentration steps or
      chemical derivatization. Most previous studies of trace compounds on the breath
      were analyzed using gas chromatography where enhanced detection sensitivity was
      achieved by concentrating the breath using cryogenic or adsorption trapping
      techniques. In this paper, we have examined volatile organic substances,
      isoprene, acetone, ammonia and ethanol in breath before and after smoking a
      cigarette. It is interesting that isoprene levels increased in all the subjects
      after smoking one cigarette with a mean increase of 70%. The mean increase for
      acetone was found to be 22%. In contrast to isoprene, a decreasing ethanol level
      was observed in all the subjects except one with the negative mean decrease of
      28%. Further SIFT-MS studies also have high-lighted some organic substances
      produced even by unburned cigarettes, US and New Zealand products. Certain US
      brands have shown much higher levels of volatile species than cigarettes produced
      in New Zealand.

PMID- 11523597
TI  - Co-oxidation of 2,2,5,7,8-pentamethyl-6-chromanol and diphenyl disulfide with 3
      chloroperoxybenzoic acid.
AB  - The aim of this study was to determine whether disulfides could serve as
      protective antioxidants for alpha-tocopherol or vice versa. The chosen reaction
      system was a co-oxidation of the model compound of alpha-tocopherol, 2,2,5,7,8
      pentamethyl-6-chromanol (PMC), and diphenyl disulfide (1) by 3
      chloroperoxybenzoic acid. The rate of oxidation of the disulfide was
      approximately twice as fast as that of PMC when each compound was oxidised
      separately. However, when they were co-oxidised, the rate of loss of PMC
      increased while that of the disulfide decreased. The reason appeared to be that
      the disulfide was preferentially oxidised to the thiosulfinate (2) and the
      thiosulfonate (3) which then reacted with unchanged PMC to form compound (4), the
      major product, and benzenethiol. Benzenethiol was then re-oxidised to the
      disulfide.

PMID- 11523598
TI  - Antioxidant activity of 5-alkoxymethyl-6-chromanols.
AB  - The 5-alkoxymethyl-2,2,7,8-tetramethyl-6-chromanols (II) are excellent
      antioxidants against autoxidising safflower oil (ASO), although not as good as
      2,2,5,7,8-pentamethyl-6-chromanol (I), the model compound of alpha-tocopherol.
      The aim of this work was to determine whether the rate of reaction of (II) with
      the radicals diphenylpicrylhydrazyl (DPP*) and galvinoxyl (ArO*) was directly
      proportional to their antioxidant activity against ASO. Compounds (II) reacted
      faster with DPP* than with ArO* but, in each case, slower than compound (I). The
      rates of reaction of I and II with both radicals followed the order I > II (R =
      H) > II (R = CH3) > II (R = other alkyls) and were directly proportional to their
      antioxidant activity against ASO.

PMID- 11523599
TI  - The 'pivotal antioxidant' hypothesis for the role of flavonoids in their
      reduction of HO* radical-induced damage on DNA.

PMID- 11523600
TI  - Phagocyte-derived reactive oxygen species and the immunology and pathology of
      murine malaria.

PMID- 11523601
TI  - Terminology of pacemaker reentrant tachycardias.

PMID- 11523602
TI  - Magnetocardiographic intra-QRS fragmentation analysis in the identification of
      patients with sustained ventricular tachycardia after myocardial infarction.
AB  - The aim of this study was to investigate if magnetocardiographic (MCG) analysis
      of cardiac micropotentials within the QRS complex can identity patients prone to
      ventricular arrhythmias, and to compare it to MCG time-domain, late-field
      analysis. The study population consisted of 136 patients with remote MI, 53 with
      and 83 without a history of VT. After averaging and high pass filtering of
      multichannel MCG signals, time-domain parameters describing the end-QRS activity
      and fragmentation index M and score S describing the whole QRS complex were
      computed. Fragmentation and time-domain parameters differed between the VT and
      control groups: fragmentation index M was 12 +/- 3 versus 9 +/- 2 (P <0.001),
      fragmentation score S was 83 +/- 42 versus 56 +/- 21 (P < 0.001), and filtered
      QRS duration was 144 +/- 32 versus 114 +/- 19 ms (P < 0.001) in VT and control
      groups, respectively. A combination of fragmentation parameters yielded 87%
      sensitivity and 61% specificity in VT identification. Corresponding figures for a
      time-domain parameter combination were 81% and 72%. Sensitivity of time-domain
      analysis was 88% and specificity was 75% in a subgroup with anterior MI. In
      multivariate analysis, fragmentation and time-domain analyses discriminated VT
      patients from controls independently of the extent of coronary artery disease or
      left ventricular dysfunction. MCG in postinfarction patients reveals pathology
      associated with propensity to ventricular arrhythmias inside and not only at the
      end of the QRS complex. MCG seems most accurate in the anterior infarct location.

PMID- 11523603
TI  - A randomized comparison of the straight linear approach with electrogram mapping
      focal approach in selective slow pathway ablation.
AB  - The aim of this study was to evaluate the efficacy and safety of the anatomic
      linear approach in selective AVN slow pathway ablation, in comparison to the
      widely used electrogram mapping focal approach. It remains undetermined whether
      or not anatomic linear ablation has a greater potential for eliminating slow
      pathway conduction than does focal ablation. Fifty consecutive patients (21 men,
      29 women, age 56 +/- 14 years) with common type AVNRT were randomly assigned to
      the linear approach (25 patients) or local electrogram mapping approach (25
      patients). A linear lesion was created between the tricuspid annulus, at the
      midlevel of the coronary sinus (CS) ostium, and the anterior aspect of the CS
      infundibulum. In 22 (88%) patients in the linear group, the AVNRT was
      successfully eliminated by 1.5 +/- 0.8 linear RF applications without any
      complications. All 25 patients in the focal group satisfied the endpoint criteria
      after 3.8 +/- 2.4 focal RF deliveries. The success rate did not significantly
      differ between the two groups. Out of the 22 patients with a successful outcome
      in the linear group, 17 (77%) attained complete abolition of the slow pathway
      conduction, whereas this was observed in only eight (32%) patients in the focal
      group (P < 0.005). The session time was significantly shorter in the linear
      group. Recurrence of the tachycardia was not documented in any patient during a
      mean follow-up of 18 +/- 8 months except one with residual slow pathway
      conduction in the focal ablation group. In conclusion, the anatomic linear
      approach can be performed safely and possesses a greater potential for slow
      pathway interruption compared to the electrogram mapping focal approach.

PMID- 11523604
TI  - Waveform optimization for internal atrial defibrillation: effects of waveform
      rounding, phase duration, and voltage swing.
AB  - The aim of this study was to compare the efficacy of internal atrial
      defibrillation by conventional truncated exponential biphasic waveforms with and
      without waveform rounding (1-2 phases) and to determine optimal duration for this
      novel double rounded waveform. Atrial fibrillation, induced by rapid electrical
      stimulation, was converted by internal shocks through defibrillation catheters
      (lateral right atrium and coronary sinus) in anesthetised sheep. Rounding the
      leading edges of the conventional biphasic waveform (Ventritex HVS-02; settings
      100/-50 V, 150/-70 V, and 200/-100 V; n = 8) reduced delivered peak and trough
      voltages, currents, and energy (by > or = 21 %, P < 0.001; for double (both
      phases) rounded) without decreasing cardioversion success. At 100/-50 V the
      efficacy of single (first phase) rounded (53 +/- 13%; mean +/- SEM) and double
      rounded (59 +/- 11%) shocks was similar to the conventional waveform (56 +/-
      14%). Double rounded waveform (phase durations 1-20 ms) efficacy was optimum at 6
      10 ms phase duration (100% success at 10-ms phase duration; 1.52 +/- 0.04 J
      delivered energy; n = 6). Successful cardioversion by conventional, single
      rounded, and double rounded biphasic waveforms (duration 6 ms each phase),
      conventional monophasic, rounded monophasic (duration 12 ms), and a damped sine
      waveform correlated strongly with peak-to-trough voltage swing within the
      waveform (r = 0.882; P < 0.01; n = 8). For internal atrial defibrillation,
      rounding both phases of the conventional biphasic waveforms, the double rounded
      waveform, permits similar efficacy to the conventional truncated exponential
      biphasic waveform at reduced peak voltage, current, and delivered energy. Optimum
      phase duration is 6-10 ms (tested range 1-20 ms).

PMID- 11523606
TI  - Adaptive filtering in exercise high resolution ECG as applied to the hypertrophic
      cardiomyopathy.
AB  - The application of adaptive filtering to ECG signals has been investigated for
      many years. This study shows that the exercise high resolution ECG (HRECG) can
      also be processed successfully in a similar way. Two groups were included
      consisting of 20 healthy individuals and 24 patients with hypertrophic
      cardiomyopathy (HCM). The HRECG parameters for both groups were similar (QRSdur:
      107 +/- 7 vs 114 +/- 18 ms NS, LAS: 25 +/- 8 vs 22 +/- 6 ms NS). In the first
      step, the HRECG signal was acquired at rest to obtain the averaged reference
      pattern. The next step was associated with peak exercise in which one could
      calculate short duration averaging (approximately 30 beats) or apply adaptive
      filtering in which the exercise component (EC) was extracted. Exercise was
      performed in the supine position on a bicycle ergometer. The load of 50 W was
      incremented by 50-W steps in 3-minute intervals and the test was ended by
      fatigue. Signals were recorded in X, Y, and Z bipolar leads with a 20-Hz high
      pass filter. The short time average QRS duration mostly was abbreviated in normal
      individuals in contrast to HCM patients in which ventricular activity prolonged
      with sensitivity, specificity, and negative and positive predictive values: 79%,
      65%, 73%, and 72%, respectively. The adaptive recurrent filtration (ARF) after
      cutoff of the EC at the level of 70 ms (this level is the EC mean value of both
      groups) showed the following statistics: 63%, 90%, 88%, and 90%. The Student's t
      test as applied to the duration of EC allowed a statistically significant
      difference between normals and HCM patients (66 +/- 4 vs 71 +/- 6 ms, P < 0.0052)
      and between HCM patients with and without ventricular tachyarrhythmia and DS (74
      +/- 6 vs 69 +/- 6 ms, P < 0.046).

PMID- 11523605
TI  - The effects of atrial electrical remodeling on atrial defibrillation thresholds.
AB  - Electrical remodeling of atrial fibrillation may account for the increase in
      atrial defibrillation thresholds over time. The aim of this study was to examine
      the time course of electrical remodeling and the benefit of early defibrillation
      on the defibrillation threshold. Twenty-six mongrel dogs weighing 27.6 +/- 3.3 kg
      were induced into AF by repeated high output burst atrial pacing. Eight dogs were
      paced for multiple time periods of 5, 20, 40, and 60 minutes. Five dogs each had
      burst pacingfor 4 hours and 8 hours, and eight dogs were paced at a high rate
      (640 beats/min) for 48 hours. Biphasic atrial defibrillation shocks with a pulse
      width of 3/3 ms synchronized to the left apical electrogram were delivered to
      coil electrode catheters positioned in the lateral left and right atria.
      Defibrillation voltage was increased from 50 V in 20- to 30-V steps until
      defibrillation was successful. As the pacing period increased, a decrease in
      atrial fibrillation cycle lengths and atrial effective refractory period was not
      observed before 8 hours. Similarly, the defibrillation threshold did not change
      significantly until the 8-hour pacing period was reached. The defibrillation
      thresholds were 69 +/- 28 V for 5 minutes, 64 +/- 20 V for 20 minutes, 99 +/- 85
      V for 40 minutes, 78 +/- 51 V for 60 minutes, 78 +/- 38 V for 4 hours, 124 +/- 33
      V for 8 hours, and 133 +/- 32 V for 48 hours (mean +/- SD) (P < 0.05). Atrial
      electrical remodeling in a rapid atrial pacing canine model is not observed until
      after 4 hours of burst atrial pacing. The atrial defibrillation threshold
      increases with increasing duration of burst atrial pacing, and follows a similar
      time course to other parameters of electrical remodeling.

PMID- 11523607
TI  - Recognition and correction of subcuticular malposition of pacemaker pulse
      generators.
AB  - Implantation of a cardiac pacemaker should be in the tissue plane deep to the
      subcutaneous tissue (i.e., between the fatty layer and the pectoralis fascia of
      the chest wall). Five patients with pacemaker implants between the cutis and the
      subcutaneous fat presented months later with chronic, unremitting, and often
      excruciating pain. The pulse generator in each case seemed excessively
      superficial and displaced, appeared too large for its known size, and was
      seemingly fixed to the overlying skin with exquisite sensitivity to light touch
      by a garment or palpation. Each had multiple consultations and treatments for
      pain, all without effect other than the temporary relief of local anesthesia. In
      three patients with obvious large subcutaneous fatty layers, the pulse generator
      was markedly superficial. Wound cultures were sterile in each case. Correction
      consisted of operative repositioning of the pulse generator into the readily
      developed subcutaneous tissue plane. In each patient, total and permanent relief
      of pain was achieved. Subcuticular positioning of permanent pacemaker pulse
      generators causes chronic pain that is readily relieved by operative
      repositioning of the pulse generator in the proper tissue plane.

PMID- 11523608
TI  - Holter monitoring in AL amyloidosis: prognostic implications.
AB  - The heart is involved in more than one third of patients with primary (AL)
      amyloidosis at diagnosis and it is by far the most common cause of death. Rhythm
      and conduction abnormalities generally represent the terminal event. The aims of
      this study were to determine the spectrum of Holter abnormalities found in AL
      amyloidosis and to assess their prognostic significance, particularly in relation
      to sudden death. Fifty-one patients with AL amyloidosis were included, and all of
      them had a complete history, physical examination, two-dimensional
      echocardiography, and 24-hour Holter monitoring. Fifty-five percent of these
      patients had echographic signs of heart involvement and 23% had heart failure.
      Complex ventricular arrhythmias were found in 57% of patients, couplets in 29%,
      and nonsustained ventricular tachycardia in 18%. Overall median survival was 23.4
      months. Congestive heart failure, echocardiographic abnormalities, and Holter
      abnormalities adversely affected survival. The multivariate analysis demonstrated
      that interventricular septum thickness and couplets were independent predictors
      of survival. The presence of couplets correlated with sudden death. Holter
      monitoring may contribute to assessing the prognosis of patients with AL
      amyloidosis.

PMID- 11523609
TI  - A randomized study on the effects of pacemaker programming to a lower output on
      projected pulse generator longevity.
AB  - The programmability of cardiac pacemakers enables the physician at follow-up to
      adjust the pacing pulse under consideration of the 100% safety margin with
      respect to the individual pacing threshold. The purpose of reducing the output is
      to prolong pacemaker longevity. The aims of this prospective, randomized trial
      were to compare the effects of nominal output versus a lower output on projected
      pacemaker longevity in single and dual chamber pacemakers. The secondary aim was
      to assess how many patients can be programmed to 2.5 V/0.4 ms instead of the
      nominal 3.5-V setting with > or = 100% safety margin. The patients received the
      same types of VVI or DDD pacemakers that were connected in the ventricle to the
      steroid-eluting, high impedance pacing lead. At the 3-month follow-up, patients
      with ventricular pacing thresholds < or = 0.15 ms at 2.5-V pulse amplitude were
      randomized to 3.5 V or 2.5 V amplitude at 0.4-ms pulse duration. Lead function
      and projected device longevity were assessed with the pacemaker's telemetry 6 and
      12 months after implantation. Of patients implanted with a VVI pacemaker, at the
      3-month follow-up, 3 patients had pacing thresholds > 0.15 ms at 2.5 V and 139
      patients could be randomized. A reprogramming to a higher output was necessary in
      one patient. The mean percentage of ventricular pacing was about 40% throughout
      the study time. The programming to 2.5-V output resulted in an insignificant
      increase of device longevity from 117.9 +/- 18.7 months in the nominal group to
      123.7 +/- 11.9 months at the 12-month follow-up (P = 0.16). Of patients implanted
      with a DDD pacemaker, 166 patients underwent randomization. The mean percentage
      of ventricular pacing was 85% in the ventricle and 35% in the atrium. The 2.5-V
      setting significantly prolonged pacemaker longevity from 98.1 +/- 21.3 to 112.0
      +/- 13.6 months (P < 0.0001). In three (1%) patients a late increase of the
      pacing threshold was observed. Due to the low ventricular pacing thresholds, the
      2.5-V/0.4-ms setting provided, 3 months after implantation, a > or = 100% safety
      margin in 99% of the patients. Programming to a lower output slightly increased
      projected pacemaker longevity compared to the nominal 3.5-V setting. Longevity
      increasedfor 5% in patients with single andfor 14% in dual chamber pulse
      generators.

PMID- 11523610
TI  - Far-field R wave oversensing in a dual chamber arrhythmia management device:
      predisposing factors and practical implications.
AB  - Initial experience with the Medtronic Jewel 7250, the ICD designed to detect and
      treat ventricular and supraventricular tachyarrhythmias, is very promising. Its
      effectiveness, however, depends on sensing performance, which has not yet been
      systematically examined. The aim of the study was to determine the incidence of,
      predisposing factors for, and practical implications of far-field R wave
      oversensing (FFRWOS) in this dual chamber ICD. During a total follow-up of 797
      months in 48 patients who had the Jewel 7250, follow-up strip charts, 12-channel
      Holter recordings and, in particular cases, Holter recordings with intracardiac
      markers were analyzed for the presence of FFRWOS. FFRWOS was documented in ten
      (21.3%) patients. Compared to other lead locations, the right atrial appendage
      lead position was most frequently associated with FFRWOS (7/27 vs 3/21, P <
      0.05). Patients with FFRWOS had significantly more treated and nontreated atrial
      episodes, many of which were judged to have been detected inappropriately. In one
      case, inappropriate atrial antitachycardia pacing due to R wave oversensing
      triggered sustained ventricular tachycardia, terminated eventually with a high
      energy shock. In dual chamber ICDs, FFRWOS may represent a frequent phenomenon
      possibly leading to serious consequences. For atrial leads, a lateral atrial wall
      position seems to be preferable. In most cases, FFRWOS can be eliminated by
      optimization of atrial sensing parameters. Given the possibility of ventricular
      proarrhythmia with atrial pacing therapy, the capability of ventricular backup
      defibrillation in respective devices is at least reassuring.

PMID- 11523611
TI  - Cycle length-associated modulation of the regional dispersion of ventricular
      repolarization in a canine model of long QT syndrome.
AB  - Previous tridimensional activation mapping showed that the development of
      functional conduction block at the onset of torsades de pointes was regionally
      heterogeneous; conduction block was frequently observed in the LV and the
      interventricular septum (IVS) but not in the RV, in the canine anthopleurin-A (AP
      A) model of long QT syndrome (LQTS). This may be related to the distribution of
      myocytes with M celllike electrophysiological characteristics. To better
      understand the regional difference of arrhythmogenicity in LQTS, the authors
      investigated cycle length related modulation of ventricular repolarization among
      three different layers: the endocardium (End), mid-myocardium (Mid), and
      epicardium (Epi) of the LV and RV and at two different areas: the Epi and septum
      (Sep) in the IVS. The LQT3 model was produced by AP-A in dogs. Using constant
      pacing and single premature stimulation (S1S2), the ventricular repolarization
      pattern was analyzed from 256 unipolar electrograms. Activation-recovery
      intervals (ARIs) were used to estimate local repolarization. In seven
      experiments, AP-A increased regional ARI dispersion to 88.1 +/- 36.0 ms in the
      LV, to 72.9 +/- 35.7 ms in the IVS, and to 23.0 +/- 8.7 ms in the RV at the
      pacing cycle length (CL) of 1,000 ms. Development of the large ARI dispersion was
      due to greater ARI prolongation at the Mid site in the LV and at Sep site in the
      IVS. As the S1S2 interval was shortened, regional ARI dispersion decreased
      gradually, and finally, ARI dispersion showed a reversal gradient of
      repolarization between the Mid and Epi sites in the LV and between the Sep and
      Epi sites in the IVS. Two factors contributed to create the reversal gradient of
      repolarization: (1) a difference in restitution kinetics at the Mid site in the
      LV and at the Sep site in the IVS, characterized by a larger delta ARI and slower
      time constant (tau), and (2) a difference in diastolic intervals at each site
      resulting in different input to restitution at the same CL. However, the RV
      showed small alteration in the transmural dispersion of repolarization in the
      S1S2 protocol. S2 created heterogeneous functional conduction block in the LV and
      IVS but not in the RV. In the LQT3 model, the arrhythmogenicity of torsades de
      pointes is primarily due to dispersion of repolarization in the LV and IVS
      because of prominent distribution of M cells. The RV seems to participate
      passively in reentrant excitation during torsades de pointes.

PMID- 11523612
TI  - A randomized, double-blind, placebo-controlled evaluation of the efficacy and
      safety of intravenously administered dofetilide in patients with Wolff-Parkinson
      White syndrome.
AB  - Pharmacological conversion of arrhythmias in Wolff-Parkinson-White (WPW) syndrome
      is often frequently undertaken. Current antiarrhythmic drugs used for conversion
      can be associated with significant side effects and variable efficacy. Fifteen
      male patients (mean age 34, range 18-63 years) with WPW syndrome and atrial
      fibrillation or AVRT induced in the electrophysiology laboratory were enrolled in
      a prospective, randomized, placebo-controlled crossover study. Patients were
      randomized to one of two doses of intravenous dofetilide or placebo. Patients who
      failed to respond to this initial infusion received a second higher dose infusion
      of dofetilide. With the initial infusion, six of ten dofetilide patients
      converted to sinus rhythm compared to one of five placebo patients. After a
      second infusion of dofetilide for placebo patients and higher dose dofetilide for
      low dose dofetilide patients, the overall conversion rate was 71% with dofetilide
      compared with 20% for placebo (P = 0.046). Atrial fibrillation converted to sinus
      rhythm in 82% of patients who received dofetilide. Intravenous dofetilide was
      safe and effective at converting induced atrial fibrillation in patients with WPW
      syndrome.

PMID- 11523613
TI  - Catheter ablation of ventricular tachycardia in patients with coronary heart
      disease: part I: Mapping.

PMID- 11523614
TI  - An unusual broad complex tachycardia: what is the diagnosis?

PMID- 11523615
TI  - Washing machine associated 50 Hz detected as ventricular fibrillation by an
      implanted cardioverter defibrillator.
AB  - This case report describes a patient with an automatic ICD who suffered a
      defibrillation shock without warning symptoms. An electrical interference can be
      observed in the stored EGM of the episode. The patient explained that the moment
      he felt the shock he was touching a washing machine. After correct grounding of
      this machine the patient did not suffer more inappropriate shocks.

PMID- 11523616
TI  - Biventricular pacing using two pacemakers and the triggered VVT mode.
AB  - Pacemaker dependent patients exhibit interventricular conduction delay due to
      right ventricular lead placement. The addition of a transvenous coronary sinus
      lead for biventricular pacing has been shown to be effective. Venous stenosis and
      thrombosis postpacemaker implantation can occur in up to 35% of patients. This
      report describes a patient with a preexisting left-sided dual chamber pacemaker
      and chronic left subclavian vein occlusion that was upgraded to a biventricular
      system byplacing a coronary sinus lead and single chamber ventricular triggered
      pacemaker on the opposite side.

PMID- 11523617
TI  - Delayed restoration of atrioventricular synchrony with beat-to-beat mode switch.
AB  - This case report describes a patient with complete AV block and a VDD pacemaker
      who experienced repetitive episodes of symptomatic bradycardia. Episodes occurred
      due to activation of an automatic beat-to-beat mode switch algorithm. After mode
      switch to VDI operation, the pacemaker failed to immediately switch back to AV
      synchronous pacing when regular sinus rhythm (> or = 100 beats per minute)
      resumed despite adequate P wave sensing. Dizziness was felt for up to several
      minutes of asynchronous pacing at the lower rate limit until VDD mode was
      restored. Episodes were completely eliminated by programming the mode switch
      function from an automatic beat-to-beat algorithm to a fixed rate algorithm.

PMID- 11523618
TI  - Electrocardiographic diagnosis of acute myocardial infarction in the presence of
      ventricular paced rhythm.
AB  - ST-segment deviation was recently described as the only ECG finding that was
      useful in the diagnosis of acute myocardial infarction during right ventricular
      pacing. This report shows that the same sign may also indicate the amount of
      myocardium in jeopardy and the coronary artery responsible.

PMID- 11523619
TI  - Lead configuration for defibrillator implantation in a patient with congenital
      heart disease and a mechanical prosthetic tricuspid valve.
AB  - The authors devised a nonthoracotomy defibrillation system for a patient with a
      prosthetic tricuspid valve using existing technology and previously established
      implantation techniques. Their lead configuration deviates substantially from
      existing designs in its primary use of a coronary sinus defibrillation coil and a
      left-sided subcutaneous array to distribute current across the ventricular
      myocardium.

PMID- 11523620
TI  - Successful prevention of recurrent ventricular fibrillation by intravenous
      isoproterenol in a patient with Brugada syndrome.
AB  - Intravenous administration of isoproterenol restored the ST-segment configuration
      to nearly normal in the right precordial leads and completely prevented
      spontaneous VF attacks in a patient with Brugada syndrome. The formation of a
      Brugada-type ECG has been attributed to the transmural dispersion of
      repolarization of the right ventricular epicardium and related to modulation of
      the autonomic nervous system. Our case may provide clues to the
      pathophysiological mechanism of this syndrome.

PMID- 11523621
TI  - Sinus node recovery after 25 years of atrial flutter.
AB  - This case report demonstrates that the sinus node can recover relatively quickly
      even after being suppressed by atrial flutter for 25 years, and that a permanent
      pacemaker may not always be necessary in all patients with sinus arrest after a
      successful atrial flutter ablation.

PMID- 11523622
TI  - Reprocessing of electrophysiology catheters: clinical studies, regulations, and
      recommendations. A report of the NASPE Task Force on Reprocessing of
      Electrophysiological Catheters. North American Society of Pacing and
      Electrophysiology.

PMID- 11523623
TI  - Tall cell papillary thyroid carcinoma metastatic to femur: evidence for thyroid
      hormone synthesis within the femur.
AB  - A 67-year old man with a 3-month history of left hip pain had a history of Graves
      disease, treated with 131I 20 years before admission, and papillary thyroid
      carcinoma, treated with cervical lymphadenopathy 9 years before admission.
      Removal of a 3.5- x 5-cm mass from the left femur revealed it to be a tall cell
      variant of papillary thyroid carcinoma. Removal of this mass resulted in his
      thyrotropin level increasing from 2 (presurgery) to 23 mIU/mL, whereas his
      thyroxine level simultaneously decreased from 5.79 (presurgery) to 2.29 microg/dL
      12 days after surgery despite continuation of levothyroxine of 0.137 mg/day. On
      histological examination, the tall cell variant in the femur was producing
      abundant thyroglobulin. This first case of a metastatic papillary thyroid
      carcinoma in bone producing thyroid hormone to the extent that the patient became
      hypothyroid after removal of this metastasis illustrates that metastatic thyroid
      lesion(s) may produce significant amounts of thyroid hormone.

PMID- 11523624
TI  - Hypercalcemia in a patient with B-cell acute lymphoblastic leukemia: a role of
      proinflammatory cytokine.
AB  - The complication of hypercalcemia is reported to occur only in 2.5-4.8% of
      patients with acute lymphoblastic leukemia (ALL). We herein report a 53-year-old
      female patient with early B-cell ALL, complicated with extreme hypercalcemia
      (15.2 mg/dL). Bone X-ray revealed osteolytic changes in many locations. Serum
      1,25(OH)2vitaminD3 and parathyroid hormone (PTH) levels were suppressed below
      normal ranges on admission. The circulating parathyroid hormone-related protein
      (PTHrP) value was within a normal range (< 1.1 pmol/L). Serum concentrations of
      tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and soluble IL-2 receptor
      were increased to 72 pg/ml, 25.3 pg/ml, and 1469 U/ml, respectively. Following
      the induction chemotherapy, the serum calcium level was promptly normalized
      accompanied with decreases in serum TNF-alpha, IL-6 and soluble IL-2 receptor
      values to 34 pg/ml, 6.35 pg/ml, and 737 U/ml, respectively. Serum PTHrP values
      remained within detectable levels. To our knowledge, this is the first case of B
      cell ALL in a patient who developed hypercalcemia with elevated concentrations of
      TNF-alpha, IL-6, and soluble IL-2 receptor, but not related to PTHrP. High
      circulating proinflammatory cytokines may have contributed to development of ALL
      induced osteolysis and hypercalcemia in the present case.

PMID- 11523625
TI  - Adult isolated hypoplasia of left pulmonary artery with exertional angina and
      abnormal exercise stress test: a case report and treatment implication.
AB  - Pulmonary artery hypoplasia, either congenital or acquired, is a rare abnormality
      seen in adults. We reported the first case of adult, isolated, left pulmonary
      artery hypoplasia, with exertional angina and prominent ST depression in exercise
      stress test, that seemed to be caused by exertional hypoxemia. Several
      vasodilators, including nitroglycerin, prostaglandin E1, and nifedipine, were
      administered individually, each with subsequent hemodynamic monitoring, pulse
      oximetric monitoring, and exercise test. Vasodilator administrations reduced
      pulmonary vascular resistance (baseline, 599; vasodilators, 306, 211, and 284
      dyne x sec x m2/cm5, respectively) and attenuated ST depression (by 52, 72, and
      27%, respectively) but without an immediate benefit on exercise tolerance. All
      vasodilators except nifedipine ameliorated exertional hypoxemia (expressed by
      arterial oxygen saturation during peak exercise, baseline, 69%; vasodilators, 85,
      78, and 65%, respectively). Additional oxygen supply after nitroglycerin
      administration further benefited exertional hypoxemia (arterial oxygen
      saturation, 96%) and exercise ST depression (attenuated by 82%).

PMID- 11523626
TI  - A case of myoedema and normal pressure hydrocephalus.
AB  - A cachectic 55-year-old man presented with ataxia and metabolic instability. On
      physical examination, he had prominent myoedema in all muscle groups. In
      addition, a CT scan and lumbar puncture showed extensive nonobstructive
      hydrocephalus. Further clinical evaluation revealed elevated creatine
      phosphokinase and liver enzyme levels, although the patient was euthyroid. The
      patient improved neurologically and metabolically with supportive therapy but the
      myoedema persisted. Previous cases have emphasized that myoedema is a localized,
      electrically silent, benign myopathic disorder of unknown cause. As with a
      previous case with ventricular enlargement, myoedema may be part of systemic
      pathology. Finally, as in most other reports, myoedema is a rare condition; only
      3 cases (of 44) with palpable (but not visible) myoedema were uncovered in this
      study.

PMID- 11523627
TI  - Prevalence of glomerulopathies in autopsies of patients infected with the
      hepatitis C virus.
AB  - BACKGROUND: Several reports have shown hepatitis C virus (HCV) infection to be
      associated with various extrahepatic manifestations, including certain forms of
      glomerulopathy. The most frequently reported glomerulonephritis in patients
      infected with HCV is either membranoproliferative glomerulonephritis (MPGN) or
      cryoglobulinemic glomerulonephritis, and HCV has been directly implicated in
      their pathogenesis. Other investigators have reported a higher prevalence of HCV
      infection in patients with membranous glomerulonephritis, IgA nephropathy, and
      focal segmental glomerulosclerosis (FSGS). However, the prevalence of these
      glomerulopathies in patients infected with HCV is unknown. METHODS: We conducted
      a 5-year retrospective review to determine prevalence of glomerulopathies in
      autopsies of patients infected with HCV. The renal histology on the autopsy
      reports was carefully reviewed for appropriate diagnosis of glomerulonephritis.
      RESULTS: Of the 114 autopsies of patients infected with HCV during this period,
      the majority had been incarcerated and had state-mandated autopsies. The mean age
      of the patients was 46.8 +/- 10 years (+/- SD; range, 19-87). Of the 114
      patients, 46 were white, 37 were African American, and 31 were Hispanic. The
      glomerulopathies seen were 3 MPGN, 2 membranous, 3 HIV-associated nephropathy, 1
      idiopathic FSGS, 1 minimal change glomerulonephritis, and 3 diabetic nephropathy.
      CONCLUSION: We conclude that although HCV is reported to be associated with
      membranoproliferative and membranous glomerulonephritis, their prevalence in
      these patients is not common.

PMID- 11523628
TI  - Multiple antibiotic changes during the first 72 hours of hospitalization.
AB  - BACKGROUND: Increasing concern about inappropriate antibiotic use prompted us to
      examine whether our patients were receiving frequent and perhaps unwarranted
      changes of antibiotic therapy. METHODS: We evaluated antibiotic prescribing by
      the physicians in the Emergency Department and by those on the inpatient medical
      service during the first 72 hours of hospitalization in 119 patients admitted
      with suspected serious infections to an acute care, university-affiliated,
      municipal teaching hospital. The appropriateness of antibiotic prescriptions was
      assessed independently and retrospectively by 2 infectious disease specialists
      (each based at a different hospital) using a 4-grade scale (from 1 = wrong choice
      to 4 = appropriate). Of their evaluations of the 427 antibiotic regimens given to
      the 119 patients during 4 defined intervals during their first 72 hours of
      hospitalization, 90% agreed with each other within 1 grade. Their evaluations
      were then compared with the selections that had been made at each interval by the
      prescribing physicians. RESULTS: Successive prescribing physicians changed the
      antibiotic regimens in 77% of cases during the first 24 hours and in 56% during
      the next 48, often without apparent clinical or microbiologic indications. By 72
      hours, the 119 patients had received a mean of 3.1 +/- 1.3 (+/-SD) different
      antibiotics, and 40 received between 4 and 7. Only 7% of the patients had no
      change in the regimen prescribed originally. CONCLUSIONS: Many patients had
      multiple changes of antibiotics, often unnecessarily, resulting in exposure to
      too many agents.

PMID- 11523629
TI  - The relationship between age and fever magnitude.
AB  - BACKGROUND: Infections are an important cause of morbidity and mortality in older
      people; however, they are often difficult to diagnose because the signs and
      symptoms of infection in older people are frequently atypical. Fever, one of the
      most important signs of infection, is a case in point. Preliminary evidence
      suggests that the febrile response in older persons is blunted, leading to the
      clinical maxim, "the older, the colder." The objective of this study was to
      assess the effect of age on the febrile response to moderate-to-severe pneumonia
      in hospitalized patients adjusted for the effect of anatomic site at which the
      temperature was measured. METHODS: This is a retrospective cohort study of 320
      hospitalized patients with moderate-to-severe pneumonia. The study was designed
      to assess the effect of age on the febrile response to moderate-to-severe
      pneumonia in hospitalized patients, adjusting for the effect of the anatomic
      location of the temperature measurement. The highest temperature of each day and
      the anatomic sites at which temperatures were taken (axillary, oral, rectal, or
      other) on days 1 and 2 of infection and at hospital discharge. Baseline
      demographic information, including age, were obtained for each patient. RESULTS:
      There were 320 patients (median age, 64 years; range, 18-97 years). Using a
      linear regression model, significant inverse correlations were found between age
      and the temperature for patients on the first and second days of hospitalization
      (P < 0.001). For each decade increase in age, the average temperature on the
      first 3 days of infection was lower by 0.15 degrees C. Temperature at discharge,
      a surrogate for baseline temperature, also decreased at an equal rate with age.
      CONCLUSION: In this study, the febrile response to infections was reduced with
      increasing age and baseline temperatures were generally lower in older patients.

PMID- 11523630
TI  - Frequency of ophthalmic assessments among elderly whites and African Americans
      with eye disease and impact on visual function.
AB  - OBJECTIVES: To study the difference in patterns of utilization of eye-care
      services among white and African American senior citizens with eye disease and
      its impact on visual function. METHODS: This study involved cross-sectional
      assessments of visual function using the Activities of Daily Vision Scale (ADVS),
      as well as retrospective self-recall of history of eye disease and frequency of
      ophthalmic assessments. Participants included 99 consecutive elderly patients
      with history of eye disease who were attending the outpatient medical clinics at
      Nassau University Medical Center, a community teaching hospital in Long Island,
      New York. RESULTS: White Americans constituted 52% of the study sample and
      African Americans constituted the remaining 48%. African American subjects were
      less likely than whites to report visiting an eye specialist over the previous 5
      years (69% versus 88%, P < 0.05). African American subjects who reported
      undergoing ophthalmic assessments over the past 5 years showed a trend of having
      higher ADVS scores (indicating better visual function) compared with those who
      did not report such history (86 +/- 12 versus 79 +/- 15, P = 0.098). On the other
      hand, reporting such history had no apparent relation to the ADVS scores in
      whites. CONCLUSIONS: African American elderly ambulatory medical patients with
      eye disease were less likely than their white counterparts to report use of eye
      care services. The use of eye-care services in African American but not white
      subjects was linked to better visual function as assessed by the ADVS.

PMID- 11523631
TI  - Mechanisms involved in tumor necrosis factor-alpha induction of insulin
      resistance and its reversal by thiazolidinedione(s).
AB  - Insulin resistance (IR) remains one of the major pathogenic mechanisms for non
      insulin-dependent type 2 diabetes mellitus. We have previously modelled IR in H
      411E liver cells in culture. In past experiments, we used both labeled glucose
      uptake, lipogenesis, and stimulation of calmodulin gene expression to quantify
      the ability of the antidiabetic drugs (pioglitazone and metformin) to reverse
      tumor necrosis factor-alpha (TNF-alpha)-induced IR in these insulin-treated
      cells. In these current experiments, H-411E liver cells were rendered IR by a
      combination of TNF-alpha and insulin. In other experiments, the ability of C2
      ceramide (Cer) to inhibit insulin action and induce IR was assessed as well as
      the phospholipase C inhibitor D609 to reverse IR induced by these TNF-alpha-like
      agents. C2 Cer, like TNF-alpha, inhibited insulin action. D609 reversed TNF-alpha
      induced--and to a lesser extent, C2 Cer-induced--IR. At selected times, the cells
      were also treated with troglitazone (TRG) in 2 groups: (1) 1-time exposure and
      (2) chronic exposure followed by acute exposure. TRG concentrations ranged from
      0.015 to 15.0 micromol/L. Our data demonstrate a powerful effect of TRG in
      reducing IR and restoring insulin sensitivity in TNF-alpha-treated H-411E cells.
      Furthermore, pretreatment with TRG, reflecting chronic exposure, as in human
      clinical use, was more potent than 1-time acute exposure. These data support the
      efficacy of using thiazolidinediones (TRG) in human type 2 diabetes, and support
      the use of this cell culture model to further study the effects of
      thiazolidinediones on TNF-alpha-induced insulin resistance.

PMID- 11523632
TI  - Factor V Leiden: a clinical review.
AB  - Factor V Leiden is the most prevalent genetic thrombophilia in people of European
      descent. Since its discovery, much clinical information has been gathered
      regarding the distribution and prevalence of the genetic mutation, the mechanism
      of thrombophilia, and its association with clinical thromboembolic events.
      Although its association with venous thromboembolism is clear, the role of Factor
      V Leiden in other disease states is not clear. A review of the literature
      regarding the mechanism of hypercoagulability, genetic versus functional
      diagnostic tests, screening issues, relationship to arterial thromboses,
      pregnancy and pregnancy complications, and treatment are discussed.

PMID- 11523633
TI  - Transnational perspectives on women's domestic work: experiences of Brazilian
      immigrants in the United States.
AB  - This article focuses on immigrant women's transnational experiences and
      perceptions of paid and unpaid domestic work. The dominance of work was an
      evident theme throughout the interviews with 26 Brazilian women who had been
      employed in domestic or food service work in the United States. Various
      intersections of gender, class, culture, and migration were evident in the
      women's changing definitions of work, measures of the quantity and quality of
      their paid and unpaid domestic work, and perceptions of their own fluid
      identities as Brazilian women, domestic workers, and immigrants. Through their
      daily lives and work experiences these immigrant women made concerted efforts to
      forge, maintain, or recreate contacts and connections with values and
      perspectives from both Brazilian and U.S. society. In the process they created
      dynamic transnational understandings and perspectives on women's domestic work.

PMID- 11523634
TI  - Job strain and self-reported health among working women and men: an analysis of
      the 1994/5 Canadian National Population Health Survey.
AB  - This paper explores the associations, for working women and men, of high strain
      jobs with self-rated health in the 1994/95 Canadian National Population Health
      Survey (NPHS). NPHS data were obtained on men (n = 4230) and women (n = 4043),
      aged 18-64 who answered an abbreviated version oF the job content questionnaire
      (JCQ). Using the upper and lower tertiles of psychological demands and decision
      latitude as cut points we classified workers into high strain and other jobs.
      Self-rated health was the outcome. We used polytomous logistic regression
      analyses and controlled for potential personal and home confounders; two risk
      parameters were estimated: for the odds of reporting poor/fair and good health
      both vs. very good/excellent health. High strain work was reported by 11% of
      women and 9% of men. After adjusting for potential confounders, high job strain
      was consistently associated with worse self-rated health in both models for each
      gender.

PMID- 11523635
TI  - Women workers confront one-eyed science: building alliances to improve women's
      occupational health.
AB  - Women suffer many health problems related to their work, but attempts to improve
      their situation face obstacles at two levels: recognition of their problems and
      ability to organize to prevent them. Recognition by occupational health
      specialists has been delayed due in part to: A perception that women's issues
      have been included in research focussed on male workers; pressure to deal with
      more visible issues of mortality and well-established illness; ignorance of
      women's working conditions; methodological biases and inadequacies. Recognition
      by unions is slowed when women and their concerns are absent from union
      membership and/or governing structures. Feminist health advocates have not often
      participated in these struggles, due to social class differences and difficulties
      in linking with some male-dominated unions. Also, due to the wide variety of
      hazardous working conditions, they do not emerge from population-based analyses
      of health determinants in the same way as do domestic violence, tobacco or
      poverty. The authors describe three alliances necessary for successful research,
      policy and practice in women's occupational health: between feminist and working
      class organizations; between feminists and occupational health scientists;
      between researchers and women workers.

PMID- 11523636
TI  - Gender differences in condom usage among rural crack-using men and women.
AB  - Consistent condom use is an important aspect of decreasing HIV transmission risk
      in heterosexual crack cocaine using populations. This study explores gender
      differences in attitudes and motivations to use condoms within a rural,
      economically disadvantaged sample. Qualitative data analysis identified recurrent
      themes regarding condom use and assessed how themes varied among men and women.
      Analyses showed that men and women exhibit different rationales for condom use,
      while both reported inconsistencies between their knowledge about safe sex,
      receptivity to condom use, and applications in practice. The findings suggest
      that prevention programs should be tailored to increase consistent condom use
      among main partners of crack smokers at risk for HIV.

PMID- 11523637
TI  - A test of factors mediating the relationship between unwanted sexual activity
      during childhood and risky sexual practices among women enrolled in the NIMH
      Multisite HIV Prevention Trial.
AB  - This study examined both the direct and indirect associations between unwanted
      sexual activity during childhood and HIV-related sexual practices of adult women.
      The sample consisted of 3,346 women recruited from sexually transmitted disease
      (STD) clinics and health service organizations. The findings demonstrated that
      participants who reported unwanted sexual activity as a child (USC) were more
      likely than women who did not report such experience to indicate that they had
      problems with alcohol, used drugs, received money or drugs in exchange for sex,
      had unwanted sex, and used mental health services. The women reporting USC also
      noted a greater number of unprotected sex acts, a greater number of partners, and
      a greater proportion of sex acts accompanied by drugs or alcohol in the past 90
      days. Mediated analyses showed that drug use, exchange of sex for money/drugs,
      unwanted sex, and to a lesser extent, problems with alcohol mediated the
      relationship between USC and unprotected sex acts, number of partners, and sex
      under the influence of drugs and alcohol. These findings suggest that
      participation in non-sexual risky behaviors among women who report USC may be a
      bridge to participation in sexual behaviors that increase their risk of HIV
      infection.

PMID- 11523638
TI  - Filipino domestic workers in Hong Kong: health related behaviors, health locus of
      control and social support.
AB  - A total of 290 female Filipino domestic helpers residing in Hong Kong completed a
      concurrent cross sectional survey designed to provide an initial report of basic
      data which measured mental health symptoms, health-related behaviors, health
      locus of control and social support. The four top ranking symptoms of mental
      distress reported included waking in the early hours, loneliness, worry and
      taking a long time to get to sleep. In general, the level of health related
      behaviors was high, with a satisfactory diet and low rates of alcohol, nicotine
      and coffee consumption. However, few women surveyed had previously had a Pap
      smear. There were also low scores for other preventive health practices.
      Reinforcement for health behaviors was seen as either a matter of chance or being
      influenced by powerful others for two thirds of the women. The conclusion
      highlights the intersection between gender, immigration and social class by
      drawing attention to issues of acceptance and accessibility of healthcare
      services for immigrant within host countries. In addition, cultural directions
      for immigrant health education are outlined.

PMID- 11523639
TI  - Women's work: volunteer AIDS care giving in northern Thailand.
AB  - Because persons with AIDS in Thailand usually are cared for by their families,
      and because government AIDS policy relies upon this assistance for the care of
      the country's sick, the research reported here addressed the questions: Who are
      the home and community care givers for PWA? What kind of care do they give? And,
      What is the impact of care giving on the care giver(s)? Informants were drawn in
      1998-99 from a long-term birth cohort study of a non-clinical urban population in
      the country's province of highest AIDS mortality, ChiangMai. The study was part
      of a larger, exploratory ethnographic study of the interplay among health,
      reproduction and development among persons born in 1964 and their mothers that I
      began in 1973. Findings include that among care-givers, parents, overwhelmingly
      mothers, and wives considered it their place, duty and moral benefit to care for
      adult children or husbands sick with AIDS.

PMID- 11523640
TI  - Predictors of social support and caregiver outcomes.
AB  - PURPOSE: This study identified predictors of caregiver's burden, satisfaction,
      depression, and social support. Little has been done to identify predictors of
      social support for caregivers at risk for negative outcomes. DESIGN:
      Correlational descriptive study. METHODS: A subset of interview data from a
      larger intervention study was utilized. Independent variables were caregiver/care
      recipient characteristics and social support. Dependent variables included
      caregiver burden, satisfaction, depression, anxiety, and hostility. RESULTS:
      Eighty-one caregiver/care-recipient dyads from the community participated in this
      study. Caregivers were women with a mean age of 67.53 years (range 39-86).
      Difficulty arranging assistance from confidante or friends correlated
      significantly and positively with caregiver burden (r = .38; p <.001) and
      depression (r = .34; p = .002), and negatively with satisfaction (r = -.28; p =
      .013). FINDINGS/IMPLICATIONS: Arranging assistance is more important than
      frequency of social network contact with respect to burden and depression. The
      findings indicate a need for further investigation and the consideration of
      interventions for at risk caregivers.

PMID- 11523641
TI  - Influence of employment characteristics on postpartum mothers' health.
AB  - BACKGROUND/PURPOSE: Over half of mothers with infants under one year are
      employed. This study explored the work experiences of women who returned to
      employment during the first year and the relationship of employment
      characteristics to maternal health. DESIGN/METHODS: Longitudinal, repeated
      measures during pregnancy and 1,4, 8, and 12 months postpartum. Data on
      employment characteristics and health status gathered between 1990-95 by
      questionnaire from 149 employed, partnered women residing in a large urban area
      in the northwestern United States. RESULTS: Work-family interference increased
      significantly between pregnancy and each postpartum occasion (p <.001). Between
      19-34% of the variance in health status at each measurement occasion was
      explained by employment characteristics. Work-family interference consistently
      contributed to the variance in health status. CONCLUSIONS: New models are needed
      to further understand the complex interplay of work and family lives.

PMID- 11523642
TI  - Women's work and symptoms during midlife: Korean immigrant women.
AB  - PURPOSE: To describe how Korean immigrant women tend to describe their work
      experiences within their daily lives and how they relate their work to the
      symptoms experienced during midlife. DESIGN: Cross-sectional study using
      methodological triangulation. Using a convenience sampling method, 119 Korean
      immigrant women were recruited for the quantitative phase, and 21 among the 119
      women were recruited for the qualitative phase. Data were collected using both
      questionnaires and in-depth interviews. The data were analyzed using descriptive
      and inferential statistics and thematic analysis. FINDINGS AND DISCUSSIONS: The
      symptoms that the women experienced during midlife were influenced by their work
      experience, which was complicated by their cultural heritage, gender issues
      embedded in their daily lives, and immigration transition. IMPLICATIONS:
      Complexities and diversities in women's work need to be incorporated in
      menopausal studies.

PMID- 11523643
TI  - Preface: women's work, health and quality of life: it is time we redefine women's
      work.

PMID- 11523644
TI  - Molecular characterisation of two novel maize LRR receptor-like kinases, which
      belong to the SERK gene family.
AB  - Genes encoding two novel members of the leucine-rich repeat receptor-like kinase
      (LRR-RLK) superfamily have been isolated from maize (Zea mays L.). These genes
      have been named ZmSERK1 and ZmSERK2 since features such as a putative leucine
      zipper (ZIP) and five leucine rich repeats in the extracellular domain, a proline
      rich region (SPP) just upstream of the transmembrane domain and a C-terminal
      extension (C) after the kinase domain identify them as members of the SERK
      (somatic embryogenesis receptor-like kinase) family. ZmSERK1 and ZmSERK2 are
      single-copy genes and show 79% identity among each other in their nucleotide
      sequences. They share a conserved intron/exon structure with other members of the
      SERK family. In the maize genome, ZmSERK1 maps to position 76.9 on chromosome arm
      10L and ZmSERK2 to position 143.5 on chromosome arm 5L, in regions generally not
      involved in duplications. ZmSERK1 is preferentially expressed in male and female
      reproductive tissues with strongest expression in microspores. In contrast,
      ZmSERK2 expression is relatively uniform in all tissues investigated. Both genes
      are expressed in embryogenic and non-embryogenic callus cultures.

PMID- 11523645
TI  - Amitrole treatment of etiolated barley seedlings leads to deregulation of
      tetrapyrrole synthesis and to reduced expression of Lhc and RbcS genes.
AB  - The effect of amitrole, known as an inhibitor of carotenoid biosynthesis, upon
      tetrapyrrole biosynthesis and its regulation has been studied. Etiolated barley
      (Hordeum vulgare L.) seedlings, grown in 125 microM amitrole, accumulated high
      levels of 5-aminolevulinate, Mg-protoporphyrin, Mg-protoporphyrin monomethyl
      ester, and protochlorophyllide. The amitrole-treated seedlings did not form
      paracrystalline prolamellar bodies, and the induction of Lhc and RbcS gene
      expression was reduced by non-photooxidative, low-intensity light. None of these
      events was observed upon treatment of the seedlings with 100 microM norflurazon,
      another inhibitor of carotenoid biosynthesis. The effect of amitrole cannot be
      explained solely by interaction with a presumed feedback inhibition of 5
      aminolevulinate synthesis since incubation with amitrole and 5-aminolevulinate
      indicated that deregulation also occurs at later steps of tetrapyrrole
      biosynthesis. A possible relationship between this deregulation and
      ultrastructural changes is discussed. In connection with previously published
      data, we discuss Mg-protoporphyrin and its monomethyl ester as possible
      candidates for a "plastid signal" that operates as a negative factor, reducing
      the expression of Lhc and RbcS genes in this higher plant.

PMID- 11523646
TI  - Roles of the fructans from leaf sheaths and from the elongating leaf bases in the
      regrowth following defoliation of Lolium perenne L.
AB  - The study of carbohydrate metabolism in perennial ryegrass (Lolium perenne L. cv.
      Bravo) during the first 48 h of regrowth showed that fructans from elongating
      leaf bases were hydrolysed first whereas fructans in mature leaf sheaths were
      degraded only after a lag of 1.5 h. In elongating leaf bases, the decline in
      fructan content occurred not only in the differentiation zone (30-60 mm from the
      leaf base), but also in the growth zone. Unlike other soluble carbohydrates, the
      net deposition rate of fructose remained positive and even rose during the first
      day following defoliation. The activity of fructan exohydrolase (FEH; EC
      3.2.1.80) was maximal in the differentiation zone before defoliation and
      increased in all segments, but peaked in the growth zone after defoliation. These
      data strongly indicate that fructans stored in the leaf growth zone were
      hydrolysed and recycled in that zone to sustain the refoliation immediately after
      defoliation. Despite the depletion of carbohydrates, leaves of defoliated plants
      elongated at a significantly higher rate than those of undefoliated plants,
      during the first 10 h of regrowth. This can be partly attributed to the transient
      increase in water and nitrate deposition rate. The results are discussed in
      relation to defoliation tolerance.

PMID- 11523647
TI  - Immunolocalization of plasma-membrane H+-ATPase and tonoplast-type
      pyrophosphatase in the plasma membrane of the sieve element-companion cell
      complex in the stem of Ricinus communis L.
AB  - Plasma-membrane-located primary pumps were investigated in the sieve element (SE)
      companion cell complex in the transport phloem of 2-week-old stems of Ricinus
      communis L. and, for comparison, in stems of Cucurbita pepo L. and in the
      secondary phloem of Agrobacterium tumefaciens-induced crown galls as a typical
      sink tissue. The plasma-membrane (PM) H+-ATPase and the tonoplast-type
      pyrophosphatase (PPase) were immunolocalized by epifluorescence and confocal
      laser scanning microscopy (CLSM) upon single or double labeling with specific
      monoclonal and polyclonal antibodies. Quantitative fluorescence evaluation by
      CLSM revealed both pumps in one membrane, the sieve-element PM. Different PM H+
      ATPase antibody clones, raised against the PM H+-ATPase of Zea mays coleoptiles,
      induced in mouse and produced in mouse hybridoma cells, discriminated between
      different phloem cell types. Clones 30D5C4 and 44B8A1 labeled sieve elements and
      clone 46E5B11D5 labeled companion cells, indicating the existence of different
      phloem PM H+-ATPase isoforms. The results are discussed in terms of energization
      of SE transporters for retrieval of leaking sucrose, K+ and amino acids, as one
      of the unknown roles of ATP found in SEs. The function of the PPase could be
      related to phloem sucrose metabolism in support of ATP-requiring processes.

PMID- 11523648
TI  - Involvement of local intercellular communication in the differentiation of zinnia
      mesophyll cells into tracheary elements.
AB  - The transdifferentiation of isolated mesophyll cells of zinnia (Zinnia elegans
      L.) into tracheary elements (TEs) has been well studied as a model of plant cell
      differentiation. In order to investigate intercellular communication in this
      phenomenon, two types of culture method were developed, in which mesophyll cells
      were embedded in a thin sheet of agarose gel and cultured on solid medium, or
      embedded in microbeads of agarose gel and cultured in liquid medium. A
      statistical analysis of the two-dimensional distribution of TEs in the thin-sheet
      cultures demonstrated their aggregation. In the microbead cultures, the frequency
      of TE differentiation was shown to depend on the local cell density (the cell
      density in each microbead): TE differentiation required local cell densities of
      more than 10(5) cells ml(-1). These results suggest that TE differentiation
      involves cell-cell communication mediated by a locally acting diffusible factor.
      This presumptive factor was characterized by applying a modified version of the
      sheet culture, which used two sheets of different cell densities, a low-density
      sheet and a high-density sheet. Differentiation of TEs in the former could be
      induced only by bringing it into contact with the latter. Insertion of a 25-kDa
      cutoff membrane between the high-density and low-density sheets severely
      suppressed such induction of TEs in the low-density sheet while a 300-kDa-cutoff
      membrane suppressed induction only slightly. Insertion of agarose sheets
      containing immobilized pronase E or trypsin also interfered with the induction of
      TEs in the low-density sheets. Thus, a proteinaceous macromolecule of 25-300 kDa
      in molecular weight was assumed to mediate the local intercellular communication
      required for TE differentiation. This substance was designated "xylogen" with
      reference to its xylogenic activity. The time of requirement for xylogen during
      TE differentiation was assessed by experiments in which cells in the low-density
      sheet were separated from xylogen produced in the high-density sheet at various
      times by insertion of a 25-kDa-cutoff membrane between the two sheets, and was
      estimated to be from the 36th hour to the 60th hour of culture (12-36 h before
      visible thickening of secondary cell walls of TEs).

PMID- 11523649
TI  - Molecular and physiological characterisation of a 14-3-3 protein from lily pollen
      grains regulating the activity of the plasma membrane H+ ATPase during pollen
      grain germination and tube growth.
AB  - A 14-3-3 protein has been cloned and sequenced from a cDNA library constructed
      from mRNAs of mature pollen grains of Lilium longiflorum Thunb. Monoclonal
      antibodies (MUP 5 or MUP 15) highly specific against 14-3-3 proteins recognised a
      30-kDa protein in the cytoplasmic fraction of many various lily tissues (leaves,
      bulbs, stems, anther filaments, pollen grains, stigmas) and in other plants
      (Arabidopsis seedlings, barley recombinant 14-3-3). In addition, 14-3-3 proteins
      were detected in a microsomal fraction isolated from pollen grains and tubes, and
      the amount of membrane-bound 14-3-3 proteins as well as the amount of the plasma
      membrane (PM) H+ ATPase increased during germination of pollen grains and tube
      growth. No change was observed in the cytoplasmic fraction. A further increase in
      the amount of 14-3-3 proteins in the microsomal fraction was observed when pollen
      grains were incubated in germination medium containing 1 microM fusicoccin (FC)
      whereas the number of 14-3-3s in the cytoplasmic fraction decreased. Fusicoccin
      also protected membrane-bound 14-3-3 proteins from dissociation after washing
      with the chaotropic salt KI. Furthermore, FC stimulated the PM H+ ATPase
      activity, the germination frequency and the growth rate of pollen tubes, thus
      indicating that a modulation of the PM H+ ATPase activity by interaction with 14
      3-3 proteins may regulate germination and tube growth of lily pollen.

PMID- 11523650
TI  - Kinetic analysis of boron transport in Chara.
AB  - The permeability of biological membranes to boric acid was investigated using the
      giant internodal cells of the charophyte alga Chara corallina (Klein ex Will.
      Esk. R.D. Wood). The advantage of this system is that it is possible to
      distinguish between membrane transport of boron (B) and complexing of B by plant
      cell walls. Influx of B was found to be rapid, with equilibrium between the
      intracellular and extracellular phases being established after approximately 24 h
      when the external concentration was 50 microM. The intracellular concentration at
      equilibrium was 55 microM, which is consistent with passive distribution of B
      across the membrane along with a small amount of internal complexation. Efflux of
      B occurred with a similar half-time to influx, approximately 3 h, which indicates
      that the intracellular B was not tightly complexed. The concentration dependence
      of short-term influx measured with 10B-enriched boric acid was biphasic. This was
      tentatively attributed to the operation of two separate transport systems, a
      facilitated system that saturates at 5 microM, and a linear component due to
      simple diffusion of B through the membrane. Vmax and Km for the facilitated
      transport system were 135 pmol m(-2) s(-1) and 2 microM, respectively. The
      permeability coefficient for boric acid in the Chara plasmalemma estimated from
      the slope of the linear influx component was 4.4 x 10(-7) cm s(-1) which is an
      order of magnitude lower than computed from the ether:water partition coefficient
      for B.

PMID- 11523651
TI  - Physiological relevance of fructose 2,6-bisphosphate in the regulation of spinach
      leaf pyrophosphate:fructose 6-phosphate 1-phosphotransferase.
AB  - A major problem in defining the physiological role of pyrophosphate:fructose 6
      phosphate 1-phosphotransferase (PFP, EC 2.7.1.90) is the 1,000-fold discrepancy
      between the apparent affinity of PFP for its activator, fructose 2,6-bisphosphate
      (Fru-2,6-P2), determined under optimum conditions in vitro and the estimated
      concentration of this signal metabolite in vivo. The aim of this study was to
      investigate the combined influence of metabolic intermediates and inorganic
      phosphate (Pi) on the activation of PFP by Fru-2,6-P2. The enzyme was purified to
      near-homogeneity from leaves of spinach (Spinacia oleracea L.). Under optimal in
      vitro assay conditions, the activation constant (Ka) of spinach leaf PFP for Fru
      2,6-P2 in the glycolytic direction was 15.8 nM. However, in the presence of
      physiological concentrations of fructose 6-phosphate, inorganic pyrophosphate
      (PPi), 3-phosphoglycerate (3PGA), phosphoenolpyruvate (PEP), ATP and Pi the Ka of
      spinach leaf PFP for Fru-2,6-P2 was up to 2000-fold greater than that measured in
      the optimised assay and Vmax decreased by up to 62%. Similar effects were
      observed with PFP purified from potato (Solanum tuberosum L.) tubers. Cytosolic
      metabolites and Pi also influenced the response of PFP to activation by its
      substrate fructose 1,6-bisphosphate (Fru-1,6-P2). When assayed under optimum
      conditions in the gluconeogenic direction, the Ka of spinach leaf PFP for Fru-1,6
      P2 was approximately 50 microM. Physiological concentrations of PPi, 3PGA, PEP,
      ATP and Pi increased Ka up to 25-fold, and decreased Vmax by over 65%. From these
      results it was concluded that physiological concentrations of metabolites and Pi
      increase the Ka of PFP for Fru-2,6-P2 to values approaching the concentration of
      the activator in vivo. Hence, measured changes in cytosolic Fru-2,6-P2 levels
      could appreciably alter the activation state of PFP in vivo. Moreover, the same
      levels of metabolites increase the Ka of PFP for Fru-1,6-P2 to an extent that
      activation of PFP by this compound is unlikely to be physiologically relevant.

PMID- 11523652
TI  - Changes in acidity and in proton transport at the tonoplast of grape berries
      during development.
AB  - As in many fruits, the induction of grape berry (Vitis vinifera L.) ripening
      results in intense breakdown of malic acid. Using membrane fractions, we tested
      the hypothesis that changes in acidity resulted from malate vacuolar
      decompartmentation. The hydrolytic activities of the two primary vacuolar pumps
      inorganic pyrophosphatase (V-PPase; EC 3.6.1.1) and vacuolar ATPase (V-ATPase; EC
      3.6.1.3) increased throughout development with an acceleration during ripening,
      as confirmed by Western blotting and analysis of transcript expression. The ratio
      of V-PPase activity to V-ATPase activity was always in favour of V-PPase and
      reached its maximum value at veraison. The rate of anion transport strongly
      increased during ripening. Before ripening, tonoplast passive permeability was
      low, but rose during ripening. Our data indicate that tonoplast leakage
      dramatically increased during ripening. This leakage is probably the prime cause
      of malate decompartmentation, amplified by the incapacity of oxidative
      phosphorylation to face increased energy demand.

PMID- 11523653
TI  - In situ localization of endogenous cytokinins during shooty tumor development on
      Eucalyptus globulus Labill.
AB  - Our previous results demonstrated that endogenous cytokinins are involved in the
      shooty potential of tumors initiated on Eucalyptus globulus plantlets inoculated
      with Agrobacterium tumefaciens strain 82.139 [A. Azmi et al. (1997a) Plant Sci
      127: 81-90]. In order to investigate whether or not these hormones are
      distributed homogeneously in the tumors prior to the onset of bud regeneration,
      decapitated hypocotyls were inoculated with the strain C58pMP90/T139 GUS-INT
      harboring the wild transferred DNA (T-DNA) of strain 82.139 tagged with the beta
      glucuronidase (gus)-reporter gene. In situ immunolocalization of zeatin,
      dihydrozeatin and isopentenyladenine was performed in the developing tumors and
      combined with the histo-enzymological beta-glucuronidase assay. It was found that
      the expression of the T-DNA was restricted to only some small areas located
      deeply in the tumors. These sites were also provided with a high cytokinin signal
      while the untransformed parts of the tumors displayed a weaker signal, except in
      the early differentiating tracheary elements. The regenerated buds were
      untransformed and originated from superficial parts of the tumors provided with a
      moderate signal for cytokinins. The method of colocalization of both cytokinins
      and gus expression developed here might be helpful for further studies concerning
      the role of these hormones in controlling gene expression at cell and tissue
      levels.

PMID- 11523654
TI  - In-situ analysis of pectic polysaccharides in seed mucilage and at the root
      surface of Arabidopsis thaliana.
AB  - Pectic polysaccharides are a complex set of macromolecules of the primary cell
      wall matrix with distinct structural domains. The biosynthesis, organisation and
      function of these domains within cell wall matrices are poorly understood. An
      immersion immunofluorescence labelling technique was developed for the in-situ
      analysis of pectic polysaccharides at the surface of seeds and seedlings of
      Arabidopsis thaliana (L.) Heynh., and used to investigate the occurrence of
      pectic homogalacturonan (HG) and rhamnogalacturonan-I (RG-I) epitopes. Seed
      mucilage appeared to consist of two regions: a highly methyl-esterified HG was a
      major component throughout the mucilage, while an inner region with relatively
      low porosity was stabilized by calcium-based HG cross-linking. The small size and
      transparency of Arabidopsis roots allowed the occurrence of pectic HG and RG-I
      epitopes at root surfaces to be directly determined on whole-mount preparations.
      Pectic epitopes were not distributed evenly over root surfaces and were notably
      absent from lateral root apices and from the surface of root hairs. The use of
      defined antibody probes in the immersion immunolabelling protocol will be useful
      for the analysis of the influence of growth conditions and genetic factors on
      pectic polysaccharides in Arabidopsis.

PMID- 11523655
TI  - Detoxification of cadmium in tobacco plants: formation and active excretion of
      crystals containing cadmium and calcium through trichomes.
AB  - In tobacco (Nicotiana tabacum L.), long and short trichomes can be distinguished
      morphologically. The established function of long trichomes is to exude a sticky
      gum containing diterpenes, whereas that of short trichomes is not known. When
      tobacco seedlings were exposed to toxic levels of cadmium (Cd), growth was
      retarded, but trichome number was increased up to 2-fold in comparison with
      untreated samples. Observation by variable-pressure scanning electron microscopy
      (VP-SEM) indicated that large crystals of 150 microm in size were formed on head
      cells of both short and long trichomes. An energy-dispersive X-ray analysis
      system fitted with VP-SEM revealed the crystals to contain amounts of Cd and
      calcium (Ca) at much higher concentrations than in the head cells themselves.
      Transmission electron microscopy demonstrated crystal formation in amorphous
      osmiophilic deposits in vacuoles. When seedlings were treated with Cd in the
      presence of Ca, tolerance was increased in proportion to the increase in Ca
      concentration. These results indicate that tobacco plants actively exclude toxic
      Cd by forming and excreting Cd/Ca-containing crystals through the head cells of
      trichomes.

PMID- 11523656
TI  - Subfractionation of eyespot apparatuses from the green alga Spermatozopsis
      similis: isolation and characterization of eyespot globules.
AB  - Despite the well-characterized function of the green-algal eyespot apparatus as a
      combined absorption/reflection screen for the photoreceptor for phototaxis,
      little is known about the proteins involved in the formation of this complex
      organelle. We therefore purified the carotenoid-rich lipid globules, which are
      the most conspicuous component of the eyespot sensu strictu from Spermatozopsis
      similis Preisig et Melkonian. Electron microscopy and an average
      carotenoid:chlorophyll ratio of 51, confirmed the high purity of the fraction.
      The diameter of isolated globules (approx. 112 nm) fell within their in vivo
      range (90-120 nm). Absorption spectra in aqueous media peaked at 535 nm. The
      predominant carotenoids were beta/psi-, beta, beta- and delta-carotene. Freeze
      fracture studies with cells and whole-mount electron microscopy of isolated
      globules demonstrated regularly arranged particles at the globule surface. Sodium
      dodecyl sulfate polyacrylamide gel electrophresis revealed specific enrichment of
      10 tightly bound major proteins and several minor proteins with the globules.
      Proteases were used to analyze their topology and function. Upon treatment with
      thermolysin, globules were released from a fraction enriched in isolated eyespot
      apparatuses. Major proteins of these globules, and those treated with thermolysin
      after isolation, were identical. However, the purified proteins were sensitive to
      thermolysin, indicating that domains of them are normally hidden in the globule
      matrix. In contrast, pronase degraded all globule-associated proteins in situ.
      These globules were not stable and easily fused, whereas thermolysin-treated
      globules were relatively stable. Lipase did not affect globule stability. These
      results indicate that the five thermolysin-resistant proteins (apparent Mr
      values: 56, 52, 32, 29, 27 kDa) are close to the surface and might be crucial for
      globule stabilization, whereas the thermolysin-accessible proteins are probably
      involved in globule/globule interactions and/or globule/eyespot-membrane
      interactions.

PMID- 11523657
TI  - Non-photosynthetic enhancement of growth by high CO2 level in the nitrophilic
      seaweed Ulva rigida C. Agardh (Chlorophyta).
AB  - The effects of increased CO2 levels (10,000 microl l(-1)) in cultures of the
      green nitrophilic macroalga Ulva rigida C. Agardh were tested under conditions of
      N saturation and N limitation, using nitrate as the only N source. Enrichment
      with CO2 enhanced growth, while net photosynthesis, gross photosynthesis, dark
      respiration rates and soluble protein content decreased. The internal C pool
      remained constant at high CO2, while the assimilated C that was released to the
      external medium was less than half the values obtained under ambient CO2 levels.
      This higher retention of C provided the source for extra biomass production under
      N saturation. In N-sufficient thalli, nitrate-uptake rate and the activity of
      nitrate reductase (EC 1.6.6.1) increased under high CO2 levels. This did not
      affect the N content or the internal C:N balance, implying that the extra N
      assimilation capacity led to the production of new biomass in proportion to C.
      Growth enhancement by increased level of CO2 was entirely dependent on the
      enhancement effect of CO2 on N-assimilation rates. The increase in nitrate
      reductase activity at high CO2 was not related to soluble carbohydrates or
      internal C. This indicates that the regulation of N assimilation by CO2 in U.
      rigida might involve a different pathway from that proposed for higher plants.
      The role of organic C release as an effective regulatory mechanism maintaining
      the internal C:N balance in response to different CO2 levels is discussed.

PMID- 11523658
TI  - Pectin secretion and distribution in the anther during pollen development in
      Lilium.
AB  - Using the monoclonal antibodies JIM 5 and 7, pectin was immunolocalized and
      quantitatively assayed in three anther compartments of Lilium hybrida during
      pollen development. Pectin levels in both the anther wall and the loculus
      increased following meiosis, were maximal during the early microspore stages and
      declined during the remainder of pollen ontogenesis. In the microspores/pollen
      grains, pectin was detectable at low levels during the microspore stages but
      accumulated significantly during pollen maturation. During early microspore
      vacuolation, esterified pectin epitopes were detected both in the tapetum
      cytoplasm and vacuoles. In the anther loculus, the same epitopes were located
      simultaneously in undulations of the plasma membrane and in the locular fluid. At
      the end of microspore vacuolation, esterified pectin epitopes were present within
      the lipids of the pollenkitt, and released in the loculus at pollen mitosis.
      Unesterified pectin epitopes were hardly detectable in the cytoplasm of the young
      microspore but were as abundant in the primexine matrix as in the loculus. During
      pollen maturation, both unesterified and esterified pectin labelling accumulated
      in the cytoplasm of the vegetative cell, concurrently with starch degradation. In
      the mature pollen grain, unesterified pectin epitopes were located in the
      proximal intine whereas esterified pectin epitopes were deposited in the distal
      intine. These data suggest that during early microspore development, the tapetum
      secretes pectin, which is transferred to the primexine matrix via the locular
      fluid. Further, pectin is demonstrated to constitute a significant component of
      the pollen carbohydrate reserves in the mature grain of Lilium.

PMID- 11523659
TI  - Sucrose transporters in two members of the Scrophulariaceae with different types
      of transport sugar.
AB  - In order to study differences between sugar transport in oligosaccharide
      translocating and sucrose-translocating species, two members of the
      Scrophulariaceae, Asarina barclaiana Pennell and Alonsoa meridionalis O. Kuntze,
      were analysed regarding minor-vein anatomy, sugar concentrations in leaves and
      phloem sap, and expression of sucrose transporters. The minor veins of Asarina
      barclaiana possess mainly transfer cells and modified intermediary cells and
      those of Alonsoa meridionalis have intermediary cells and ordinary companion
      cells. Phloem sap from these plants was collected by the laser-aphid-stylet
      technique. The main carbon transport forms in Asarina were sucrose and in Alonsoa
      raffinose and stachyose. The sum of the carbohydrate concentrations in the phloem
      sap of both species was as high as that in apoplastic phloem loaders. In Asarina
      the ratio of the sucrose concentration in the phloem to that in the cytosol of
      source cells was about 35 and the corresponding ratio in Alonsoa was about two.
      Sucrose transporter cDNAs were isolated from leaves of both species. By means of
      semi-quantitative reverse transcription-polymerase chain reaction, sucrose
      transporter mRNA was detected in different organs and also in the phloem sap.
      This is the first time that sucrose transporters have been found in
      oligosaccharide-translocating species and that the mRNA of these sucrose
      transporters has been localized directly in the phloem sap. Taken together, our
      observations indicate that Asarina is an apoplastic phloem loader, while the
      results for Alonsoa are ambiguous: some properties are typical of the symplastic
      phloem-loading mechanism, but probably a sucrose transporter is involved in
      loading and/or retrieval of sucrose into the phloem.

PMID- 11523661
TI  - When worlds collide.

PMID- 11523660
TI  - Auxin-induced elongation of short maize coleoptile segments is supported by 2,4
      dihydroxy-7-methoxy-1,4-benzoxazin-3-one.
AB  - Endogenous extractable factors associated with auxin action in plant tissues were
      investigated, especially their effects on elongation of 1-mm coleoptile segments
      of maize (Zea mays L.), in the presence of saturating 10 microM indole-3-acetic
      acid (IAA). The relative growth response, to auxin alone, was much smaller in
      segments shorter than 2-3 mm compared to 10-mm segments. Fusicoccin-induced
      elongation, however, was less affected by shortening the segments. A reduced
      auxin response may result from the depletion through cut surfaces of a substance
      required for IAA-mediated growth. Sucrose, phenolics like flavonoids, and
      vitamins were ruled out as the causal factors. A partially purified methanol
      extract of maize coleoptiles supported longterm, auxin-controlled elongation. The
      active material was also found among substances bleeding from scrubbed maize
      coleoptiles. The active factor from maize was further purified by HPLC and
      characterised by the UV spectrum and its pH shift. This factor was identified as
      2,4-dihydroxy-7-methoxy-1,4-benzoxazin-3-one (DIMBOA) by mass spectroscopy.
      Activity tests confirmed that pure DIMBOA from other sources sustained auxin
      induced elongation of short maize coleoptile segments. However, DIMBOA only
      partially restored the activity lost from short segments. This indicates that an
      additional factor, other than DIMBOA, is required. Extracts from Avena or
      Cucurbita did not contain the factor DIMBOA; it was active on maize elongation,
      but not on Avena coleoptiles or Cucurbita hypocotyls. This narrow specificity and
      the lack of DIMBOA action in short-term tests with maize indicate that DIMBOA is
      not the general auxin cofactor but may specifically "spare" the co-auxin in
      maize.

PMID- 11523662
TI  - The oath of Hippocrates: an historical review.
AB  - This presentation is designed to share with fellow neurosurgeons a topic, namely
      the oath of Hippocrates, that has been a subject of fascination to physicians,
      scholars, historians, and even the public for the past 2500 years. Its moral and
      ethical message has exhibited remarkable resiliency through the ages, in varied
      cultures. Although its language may appear odd, its precepts are as valid today
      as they were in Hippocrates' time. This can be best understood through an
      historical review of the oath's transmission and acceptance in different eras of
      western history. The longevity of the oath, however, is clearly attributable to
      its intrinsic merit, its high moral reverent tone, and a literary eloquence that
      placed Hippocrates among the best writers of antiquity. Despite the fame of its
      author, the oath has experienced a life of its own, from relative obscurity
      during the Dark Ages to reverential study since the Renaissance. Five aspects are
      considered in this discussion, i.e., 1) oaths in antiquity; 2) a biographical
      sketch of Hippocrates; 3) the chain of transmission from antiquity to modern
      times; 4) comments on other oaths, prayers, codes, and credos; and 5) an analysis
      and some personal views of the oath.

PMID- 11523663
TI  - Sine qua non: the formulation of a theory of neurosurgery.
AB  - Fundamental postulates underlying the fabric of biomedicine are rarely discussed,
      much less seen in print. Scientific surgery and its subspecialties are relatively
      new fields, and their philosophical basis has received little attention since
      Halsted's day. During the last quarter century, we have "reinvented"
      neurosurgery, and a concatenation of forces is escalating that is further
      accelerated by technological change. Social, economic, political, and scientific
      climates concurrently exert unusually stressful influences on all practitioners,
      irrespective of the individual setting. This provides a reason to reexamine what
      neurosurgeons do and why, and to attempt to define the guidelines of theoretical
      basis for the specialty of neurosurgery and its procedures. This article examines
      the accomplishments of past generations in an effort to establish surgical
      substrata and proceeds to attempt to readdress elements of a theoretical basis of
      our current practice.

PMID- 11523664
TI  - Transplantation of embryonic dopaminergic neurons.

PMID- 11523665
TI  - Is transplantation to treat Parkinson's disease dead?

PMID- 11523666
TI  - Cell transplantation in Parkinson's disease: implications for human clinical
      trials.

PMID- 11523667
TI  - Fetal cell implantation to treat Parkinson's disease: questions for the future.

PMID- 11523668
TI  - Serial [18F] fluorodeoxyglucose positron emission tomography after human neuronal
      implantation for stroke.
AB  - OBJECTIVE: There is no known effective treatment for chronic stroke. In this
      report, we used positron emission tomography (PET) with [18F]fluorodeoxyglucose
      (FDG) to map the metabolic brain response to neuronal cell implantation in the
      first human neuroimplantation trial for stroke. METHODS: Twelve patients (nine
      men, three women; mean age +/- standard deviation, 60.8+/-8.3 yr) with chronic
      basal ganglia infarction and persistent motor deficit underwent FDG PET within 1
      week before and 6 and 12 months after stereotactic implantation of human neuronal
      cells. Serial neurological evaluations during a 52-week postoperative period
      included the National Institutes of Health stroke scale and the European stroke
      scale. RESULTS: Alterations in glucose metabolic activity in the stroke and
      surrounding tissue at 6 and 12 months after implantation correlated positively
      with motor performance measures. CONCLUSION: FDG PET performed as part of an
      initial open-label human trial of implanted LBS-Neurons (Layton BioScience,
      Sunnyvale, CA) for chronic stroke demonstrates a relationship between relative
      regional metabolic changes and clinical performance measures. These preliminary
      findings suggest improved local cellular function or engraftment of implanted
      cells in some patients.

PMID- 11523669
TI  - Prophylactic hyperdynamic postoperative fluid therapy after aneurysmal
      subarachnoid hemorrhage: a clinical, prospective, randomized, controlled study.
AB  - OBJECTIVE: To investigate the role of prophylactic hyperdynamic postoperative
      fluid therapy in preventing delayed ischemic neurological deficits attributable
      to cerebral vasospasm. METHODS: We designed a prospected, randomized, controlled
      study and included 32 patients with subarachnoid hemorrhage. Sixteen patients
      received hypervolemic hypertensive hemodilution fluid therapy; the other 16
      patients received normovolemic fluid therapy. All patients were monitored for at
      least 12 days, with clinical assessments, transcranial Doppler recordings, single
      photon emission computed tomographic (SPECT) scanning, and routine computed
      tomographic scanning. For fluid balance monitoring, a number of blood samples
      were obtained on a daily basis and continuous central venous pressure and mean
      arterial blood pressure measurements were performed for both groups. All patients
      received intravenous nimodipine infusions between Day 1 and Day 12. End points of
      this study were clinical outcomes, clinically evident and transcranial Doppler
      sonography-evident vasospasm, SPECT findings, complications, and costs. Clinical
      examinations (using the Glasgow Outcome Scale) performed 1 year after discharge,
      together with neuropsychological assessments and SPECT scanning, were the basis
      for the evaluation of clinical outcomes. RESULTS: No differences were observed
      between the two groups with respect to cerebral vasospasm (as observed clinically
      or on transcranial Doppler recordings). When regional cerebral blood flow was
      evaluated by means of SPECT analysis performed on Day 12 after subarachnoid
      hemorrhage, no differences were revealed. One-year clinical follow-up assessments
      (with the Glasgow Outcome Scale), including SPECT findings and neuropsychological
      function results, did not demonstrate any significant group differences. Costs
      were higher and complications were more frequent for the hyperdynamic therapy
      group. CONCLUSION: Neither early nor late outcome measures revealed any
      significant differences between the two subarachnoid hemorrhage treatment models.

PMID- 11523670
TI  - Risk factors for subarachnoid hemorrhage.
AB  - OBJECTIVE: Cigarette smoking has been demonstrated to increase the risk of
      subarachnoid hemorrhage (SAH). Whether cessation of smoking decreases this risk
      remains unclear. We performed a case-control study to examine the effect of
      smoking and other known risk factors for cerebrovascular disease on the risk of
      SAH. METHODS: We reviewed the medical records of all patients with a diagnosis of
      SAH (n = 323) admitted to Johns Hopkins Hospital between January 1990 and June
      1997. Controls matched for age, sex, and ethnicity (n = 969) were selected from a
      nationally representative sample of the Third National Health and Nutrition
      Examination Survey. We determined the independent association between smoking
      (current and previous) and various cerebrovascular risk factors and SAH by use of
      multivariate logistic regression analysis. A separate analysis was performed to
      determine associated risk factors for aneurysmal SAH. RESULTS: Of 323 patients
      admitted with SAH (mean age, 52.7+/-14 yr; 93 were men), 173 (54%) were
      hypertensive, 149 (46%) were currently smoking, and 125 (39%) were previous
      smokers. In the multivariate analysis, both previous smoking (odds ratio [OR],
      4.5; 95% confidence interval [CI], 3.1-6.5) and current smoking (OR, 5.2; 95% CI,
      3.6-7.5) were significantly associated with SAH. Hypertension was also
      significantly associated with SAH (OR, 2.4; 95% CI, 1.8-3.1). The risk factors
      for 290 patients with aneurysmal SAH were similar and included hypertension (OR,
      2.4; 95% CI, 1.8-3.2), previous smoking (OR, 4.1; 95% CI, 2.7-6.0), and current
      smoking (OR, 5.4; 95% CI, 3.7-7.8). CONCLUSION: Hypertension and cigarette
      smoking increase the risk for development of SAH, as found in previous studies.
      However, the increased risk persists even after cessation of cigarette smoking,
      which suggests the importance of early abstinence from smoking.

PMID- 11523671
TI  - Blood clot resolution in human cerebrospinal fluid: evidence of first-order
      kinetics.
AB  - OBJECTIVE: To determine the kinetics of blood clot resolution in human
      cerebrospinal fluid. METHODS: Computed tomographic scans of 17 adult patients
      with intraventricular hemorrhages were analyzed. Intraventricular clot volume was
      determined and analyzed over time to determine both a standardized percentage
      rate and an absolute rate of clot resolution. Results were analyzed by use of
      regression for cross sectional time-series data. To determine the kinetics of
      intraventricular clot resolution, the effect of the clot volume on the percentage
      rate of clot resolution, clot half-life, and absolute rate of clot resolution was
      analyzed. The potential effect of age, sex, type of hemorrhage, and treatment
      with external ventricular drainage on the percentage rate of clot resolution was
      assessed. RESULTS: The percentage rate of clot resolution was 10.8% per day (95%
      confidence interval, 9.05-12.61 %), and it was independent of initial clot
      volume, age, sex, type of underlying hemorrhage, and use of external ventricular
      drainage. The absolute rate of clot resolution varied directly with the maximal
      clot volume (R2 = 0.88; P < 0.001). The percentage clot resolution data are
      consistent with events during the first 24 to 48 hours that antagonize clot
      resolution. CONCLUSION: These findings demonstrate that intraventricular blood
      clot resolution in patients with intraventricular hemorrhage follows first-order
      kinetics. The thrombolytic enzyme system responsible for intraventricular clot
      resolution seems to be saturated at 24 to 48 hours after the initial hemorrhage.

PMID- 11523672
TI  - Nitric oxide and subarachnoid hemorrhage: elevated level in cerebrospinal fluid
      and their implications.
AB  - OBJECTIVE: Nitric oxide (NO) plays an important role in the pathogenesis of
      neuronal injury after brain ischemia, and decreased levels of NO have been
      implicated in the pathogenesis of vasospasm after subarachnoid hemorrhage (SAH).
      In this study, we measured the ventricular cerebrospinal fluid (CSF) NO levels in
      patients with SAH and correlated the levels with clinical grade and middle
      cerebral artery velocities measured with transcranial Doppler ultrasound.
      METHODS: All patients with spontaneous SAH documented on computed tomography and
      with an external ventricular drain inserted within 24 hours of hemorrhage were
      included in the study. A total of 16 patients were studied between August 1999
      and August 2000. CSF was collected serially at the time of surgery and
      subsequently at daily intervals. It was collected during the time that the
      external ventricular drain remained patent and in situ. NO levels were measured
      by photometric analysis by using a nitrite/nitrate assay kit (Cayman Chemical,
      Ann Arbor, MI). RESULTS: The peak NO level in patients with SAH ranged from 9.96
      to 168.16 micromol, with a median of 36.93 micromol. The levels were
      significantly elevated as compared with the control group (5.16 micromol, P <
      0.05). The median NO level in patients with poor-grade SAH was 67.14 micromol as
      compared with 27.42 micromol in patients with good-grade hemorrhage (P < 0.05).
      No correlation was seen between CSF NO levels and middle cerebral artery
      velocities. The median NO level was 33.2 micromol in patients with a poor outcome
      as compared with 30.25 micromol in patients with a good outcome (P > 0.05).
      CONCLUSION: This study showed that NO levels are elevated after spontaneous SAH,
      and the degree of elevation is higher in patients with poor-grade SAH.

PMID- 11523673
TI  - A new mode of percutaneous upper thoracic phenol sympathicolysis: report of 50
      cases.
AB  - OBJECTIVE: Our previous study demonstrated that a high concentration of phenol
      (75-90%) with minimal volume (0.02 ml) can elicit serious degeneration of
      ganglion cells of the stellate ganglia in cats. Another previous study in our
      clinical patients demonstrated that approximately 84 to 90% of the upper thoracic
      (T2-T3) sympathetic trunks can be found under an endoscope on the ventral side of
      the T2-T3 rib heads. In this report, we present a new mode of dorsal percutaneous
      thoracic phenol sympathicolysis (PTPS) for the treatment of palmar hyperhidrosis
      or axillary bromidrosis. METHODS: Fifty patients with palmar hyperhidrosis or
      axillary bromidrosis were injected with 75% phenol into a total of 98 sides of
      the T2-T3 or T3-T4 sympathetic trunks and ganglia. The injected volume was 0.6 to
      1.2 ml (average, 0.8 ml) for each side. The technique of dorsal percutaneous
      injection was performed under local anesthesia or local with intravenous general
      anesthesia and under the guidance of a C-arm fluoroscope. RESULTS: Forty patients
      (80%) showed satisfactory results, including cessation of sweating. The success
      rates of PTPS were 83.7% (41 of 49 patients) on the left side and 91.8% (45 of 49
      patients) on the right side. The skin temperature of the thumb increased by 5.3
      to 5.4 degrees C approximately 1 hour after the phenol injection in patients with
      satisfactory results, whereas it increased by only 1.3 to 2.7 degrees C in
      patients who had unsatisfactory results. CONCLUSION: PTPS may be a good
      alternative to endoscopic sympathectomy to treat palmar hyperhidrosis and
      axillary bromidrosis. The skin temperature of the thumb is still a useful index
      to evaluate preliminarily whether PTPS has been successful.

PMID- 11523674
TI  - Incidentally identified syringomyelia associated with Chiari I malformations: is
      early interventional surgery necessary?
AB  - OBJECTIVE: The purpose of this study was to analyze clinical data and magnetic
      resonance imaging (MRI) findings for patients with asymptomatic, incidentally
      identified syringomyelia associated with Chiari I malformations who were
      monitored for more than 10 years, and to clarify the natural history of these
      lesions. METHODS: The clinical records of nine patients who had not been
      surgically treated and were regularly subjected to neurological and MRI
      examinations were analyzed. In MRI studies, the axial diameter of the syrinx at
      the widest level, the longitudinal extent of the syrinx, and the extent of
      tonsillar herniation into the spinal canal were analyzed. As a control, MRI
      findings for 11 patients with symptomatic syringomyelia associated with Chiari I
      malformations who had been surgically treated were also analyzed, and these MRI
      parameters were statistically compared between the asymptomatic and symptomatic
      groups. RESULTS: One patient underwent surgery, because of neurological changes,
      7 years after the first visit. None of the remaining patients demonstrated any
      neurological change during the follow-up period (11.2+/-0.7 yr), and all of them
      have been faring well without surgery. No statistically significant differences
      in MRI findings between the asymptomatic and symptomatic groups were observed.
      CONCLUSION: The long-term clinical courses of patients with asymptomatic,
      incidentally identified syringomyelia associated with Chiari I malformations were
      observed to be benign. MRI parameters did not provide predictable values to
      recommend interventional surgery. Unless changes in neurological or MRI findings
      are detected, early interventional surgery is not necessary.

PMID- 11523675
TI  - Carotid endarterectomy with regional anesthesia.
AB  - The senior author (REH) has changed his technique for performing carotid
      endarterectomy from the use of general anesthesia to the use of cervical block
      anesthesia. Because a randomized study was not performed, it is difficult to
      separate effects of increased surgical experience from those caused by a change
      in anesthetic regimen. Nonetheless, there has been a substantial decrease in
      complications, length of hospital stay, and costs concomitant with the change to
      regional anesthesia; we think there is a causal relationship. The use of cervical
      block anesthesia has practically eliminated the non-stroke-related complications
      associated with carotid endarterectomy in our practice. The technique for
      performing carotid endarterectomy under cervical block anesthesia is described in
      detail.

PMID- 11523676
TI  - Cerebral revascularization using radial artery grafts for the treatment of
      complex intracranial aneurysms: techniques and outcomes for 17 patients.
AB  - OBJECTIVE: The goal of this report is to illustrate the use of radial artery
      grafts as bypass conduits in the management of complex intracranial aneurysms and
      to describe a new "pressure distension technique" to eliminate postoperative
      vasospasm, which was a common problem early in our experience. METHODS: This
      study included a series of 17 patients who were surgically treated between 1994
      and January 2001 for complex intracranial aneurysms. Five patients were
      surgically treated without the pressure distension technique; for 12 patients,
      the technique was used to reduce postoperative vasospasm. Fourteen of the
      patients had anterior circulation aneurysms, and three had posterior circulation
      aneurysms. Five of the patients had undergone previous attempts at direct
      clipping or excision and reconstruction of the aneurysm in question, and
      embolization had been performed for one patient with a carotid-cavernous fistula.
      Thirteen patients underwent permanent revascularization combined with proximal
      occlusion, trapping, or clipping, and four patients underwent temporary
      revascularization for cerebral protection during anticipated prolonged occlusion
      of the parent vessel during aneurysm dissection. Surgical techniques are
      described, with particular reference to vessel collection and bypass techniques.
      RESULTS: The outcomes for this group of patients, considering the complexity of
      the aneurysms and their "inoperability," with respect to direct clipping, were
      satisfactory. The aneurysms were completely obliterated for all patients, and the
      grafts were patent for all except one patient on postoperative angiograms. There
      were two deaths, one attributable to systemic sepsis and the other attributable
      to cardiac arrest during a transbronchial biopsy. The postoperative Glasgow
      Outcome Scale scores were either better or the same for all other patients,
      compared with their preoperative scores. Three of the five patients treated
      before the institution of the pressure distension technique experienced vasospasm
      of the graft, with two of those patients requiring angioplasty. For one of those
      patients, angioplasty led to rupture of the graft. Vasospasm was not observed for
      any of the 12 patients for whom the pressure distension technique was used. We
      observed no morbidity related to radial artery collection. CONCLUSION:
      Revascularization techniques are occasionally necessary for the surgical
      treatment of complicated intracranial aneurysms. The merits of the use of the
      radial artery as a bypass conduit are discussed. Radial artery grafts should be
      considered as alternatives to saphenous vein and superficial temporal artery
      grafts. The problem of vasospasm of the artery has been solved with the pressure
      distention technique.

PMID- 11523677
TI  - Image-guided placement of eye muscle electrodes for intraoperative cranial nerve
      monitoring.
AB  - OBJECTIVE: Monitoring of the oculomotor system during cranial base or brainstem
      surgery requires extraocular intraorbital insertion of electromyography
      electrodes. We investigated the use of image-guidance technology for anatomically
      correct intraorbital electrode placement. METHODS: For neuronavigation, an
      optical tracking system was used in a standard fashion. Needle electrodes were
      inserted percutaneously into the lateral rectus, inferior rectus, and superior
      oblique muscle along the axis of a hand-held pointer or by means of an electrode
      applicator to allow direct tracking with the navigation system. Electromyographic
      monitoring was performed by multichannel recordings of free running or evoked
      activity from the selected muscles. RESULTS: We have used this method in 10
      patients; 5 had cranial base tumors and 5 underwent operations for brainstem
      lesions. No additional instruments or resources were required compared with the
      routine setup, and no intraorbital structures were injured. Successful monitoring
      of oculomotor, trochlear, or abducent nerve function was possible in each case.
      CONCLUSION: This method may have the potential to increase the safety and success
      rate of intraoperative electro-ophthalmography during microsurgery focused on
      preservation of neurological function.

PMID- 11523678
TI  - Surgical exposure and resection of the vertical portion of the petrous internal
      carotid artery: anatomic study.
AB  - OBJECTIVE: The goals were to determine which surgical approaches, i.e., the
      preauricular subtemporal infratemporal fossa (PSI), postauricular transtemporal
      (PAT), and/or subtemporal middle fossa (SMF) approaches, provide optimal exposure
      of the anterior, posterior, medial, and lateral aspects of the vertical segment
      of the petrous internal carotid artery (VPCA) and to determine the length of the
      VPCA that can be resected before a vein graft is necessary. METHODS: Using 22
      cadaveric specimens, we compared the length of exposure of the VPCA provided by
      the PSI, PAT, and SMF approaches. The segment of the VPCA that was exposed with
      each approach was measured in millimeters and expressed as a percentage of the
      total length of the VPCA. Resection of the VPCA in 1-mm increments was performed
      until a graft would be necessary; the total length of the resected segment was
      recorded in millimeters and was also expressed as a percentage of the total
      length of the VPCA. RESULTS: The PSI approach provided average exposures of 14.1
      mm (95% of the total exposure possible) of the anterior aspect and 14.3 mm (96%)
      of the lateral aspect of the VPCA; resection of less than 2.3 mm (16%) of the
      VPCA could be repaired with an end-to-end anastomosis. The PAT approach provided
      average exposures of 10.5 mm (71 %) of the lateral aspect and 10.0 mm (76%) of
      the posterior aspect of the VPCA; resection of less than 2.8 mm of the VPCA could
      be repaired with an end-to-end anastomosis. The SMF approach provided average
      exposures of 6.1 mm (45%) of the anterior aspect and 5.4 mm (41 %) of the lateral
      aspect of the VPCA; resection of less than 2.4 mm (24%) of the VPCA could be
      repaired with an end-to-end anastomosis. CONCLUSION: Lesions on the anterior and
      lateral aspects of the VPCA can be fully exposed with the PSI approach or
      partially exposed with the less invasive SMF approach. Lesions on the posterior
      aspect of the artery are best exposed with the PAT approach. Lesions on the
      medial aspect of the VPCA cannot be exposed unless the VPCA is mobilized in the
      PSI approach. Resection of less than approximately 2.5 mm (20%) can be repaired
      with an end-to-end anastomosis, regardless of the approach used.

PMID- 11523679
TI  - Vascular smooth muscle cell differentiation in human cerebral vascular
      malformations.
AB  - OBJECTIVE: The pathogenesis of central nervous system vascular malformations
      likely involves the abnormal assembly, differentiation of vascular smooth muscle
      cells (VSMC), or both in association with dysmorphic vessel wall. We hypothesize
      that intracranial arteriovenous malformations (AVMs) and cerebral cavernous
      malformations (CCMs) exhibit distinct patterns of expression of molecular markers
      of differentiation and maturity of VSMCs. We further speculate that the unique
      VSMC phenotype in the different lesions is not necessarily maintained in cell
      culture. METHODS: Paraffin-embedded sections of five AVMs, CCMs, and control
      brain tissues were stained immunohistochemically with antibodies to alpha-smooth
      muscle actin (alpha-SMA), myosin heavy chain, and smoothelin, a novel marker for
      contractile VSMC phenotype. Large (> or =100 microm) and small (<100 microm)
      vessels were counted and assessed for immunoexpression of each protein, then
      categorized according to expression of one or more of these markers. Cultured
      nonendothelial cells isolated from four other excised AVM and CCM lesions were
      assessed for immunoexpression of the same antibodies. RESULTS: Alpha-SMA was
      universally expressed in all vessels in AVMs and in control brains. It was
      expressed in the subendothelial layer of 97% of large caverns and 85% of small
      caverns and in scattered intercavernous connective tissue fibrocytes in CCMs.
      Myosin heavy chain was expressed in the majority of brain and AVM vessels, except
      for normal veins, and in the subendothelial layer of more than half of the
      caverns in CCMs. Smoothelin expression was less prevalent in large vessels in
      AVMs than in control brains and was not found in any caverns in CCMs (large
      vessels in control brains, 40.9%; AVMs, 21.9%; CCMs, 0%; P < 0.0001). Cultured
      AVM and CCM nonendothelial cells expressed alpha-SMA, but myosin heavy chain was
      expressed weakly in cells from only one CCM. Smoothelin was negative in all
      cells. CONCLUSION: We describe vessels with various stages of VSMC
      differentiation in AVMs and CCMs. The subendothelial layer of CCMs commonly
      expresses alpha-SMA and less commonly expresses myosin heavy chain. Expression of
      smoothelin was less prevalent in large AVM vessels than in normal brain, which
      may reflect the loss of contractile property associated with hemodynamic stress.
      It is difficult to evaluate VSMC differentiation in culture because of phenotypic
      change.

PMID- 11523680
TI  - Immunomodulation of glioma cells after gene therapy: induction of major
      histocompatibility complex class I but not class II antigen in vitro.
AB  - OBJECTIVE: Acquired immunity has been demonstrated in Fischer rats bearing
      syngeneic 9L tumors after herpes simplex virus (HSV) thymidine kinase (TK) gene
      transfection and ganciclovir treatment. The nature of this immunity in rats and
      its relevance to the HSV TK/ganciclovir protocol for human subjects remain to be
      determined. In this study, levels of major histocompatibility complex (MHC) Class
      I and II antigen expression were measured before and after HSV TK transfection,
      in an effort to document immunomodulatory changes caused by gene therapy.
      METHODS: Tumor cells from the 9L gliosarcoma cell line, three primary human
      glioma cultures, and the human glioma cell line U87 MG were transduced with HSV
      TK vector-containing supernatant from fibroblast-producing cells (titer of 5 x
      10(6) colony-forming units/ml) and selected in G418 medium for neomycin
      resistance. Clones were pooled or individually selected for cell-killing assays
      with ganciclovir, to confirm TK expression (10(3) cells/well in a 96-well dish).
      Northern analyses using MHC Class I and Class II complementary deoxyribonucleic
      acid probes were performed on blots containing total ribonucleic acid from wild
      type tumor cells and HSV TK transfectants. A beta-actin complementary
      deoxyribonucleic acid probe served as an internal control. Cell surface
      expression was confirmed with flow cytometry. The induction of MHC Class I was
      tested for cycloheximide and genistein sensitivity. RESULTS: All cell cultures
      exhibited increases in MHC Class I but not MHC Class II expression, as determined
      by Northern analysis densitometry and flow cytometry. Cycloheximide treatment did
      not diminish the up-regulation of MHC Class I after retroviral transfection,
      implicating a signal transduction pathway that does not require ongoing protein
      synthesis. Genistein pretreatment of cell cultures did diminish the up-regulation
      of MHC Class I, implicating a tyrosine kinase in the signaling cascade.
      CONCLUSION: Induction of MHC Class I in rat and human glioma cells after HSV TK
      retroviral gene therapy is a primary effect that is dependent on tyrosine kinase
      activity. Specific immune responses generated after transfection may represent an
      important general side effect of gene therapy protocols. Elucidation of the
      mechanism of immunomodulation after gene therapy will likely yield safer and more
      effective clinical protocols.

PMID- 11523681
TI  - Transforming growth factor beta-coated platinum coils for endovascular treatment
      of aneurysms: an animal study.
AB  - OBJECTIVE: To test the hypothesis that coating platinum coils with transforming
      growth factor beta (TGFbeta) would improve the cellular proliferation within
      experimental aneurysms relative to uncoated coils. MATERIALS AND METHODS:
      Elastase-induced saccular aneurysms were created in 12 New Zealand White rabbits.
      These aneurysms were embolized with platinum coils, either "control" (unmodified)
      coils or "test" (coated with TGFbeta) coils. Subjects were killed either 2 weeks
      (n = 3, control; n = 3, test) or 6 weeks (n = 3, control; n = 3, test) after
      embolization. Aneurysm tissue was embedded in plastic, sectioned, and stained
      with hematoxylin and eosin. The thickness of tissue covering the coils at the
      coil-lumen interface was measured by use of a digital microscope, and was
      compared between groups by use of the Student's t test (P < or = 0.05). RESULTS:
      Two-week implantation samples demonstrated mean thickness of tissue overlying
      TGFbeta-coated coils of 36+/-15 microm and mean thickness of overlying control
      coils of 3+/-5 microm, indicating significantly thicker tissue growth covering
      test versus control coils (P = 0.02). Six-week implantation samples demonstrated
      mean thickness of tissue overlying TGFbeta-coated coils of 86+/-74 microm versus
      mean thickness overlying control coils of 37+/-6 mu; this difference did not
      reach statistical significance (P = 0.30). Thickness of tissue covering TGFbeta
      coated coils did not change significantly from 2 to 6 weeks (P = 0.31). Tissue
      thickness over control coils increased significantly between 2 and 6 weeks (P =
      0.002). CONCLUSION: TGFbeta-coated platinum coils undergo earlier cellular
      coverage than standard platinum coils, but differences in coverage between coated
      and control coils are no longer present at later time points. These data suggest
      that improvements in intra-aneurysmal cellular proliferation resulting from coil
      modifications, although significant in the early postembolization phase, may
      dissipate over time.

PMID- 11523682
TI  - Effects of centrally administered arginine vasopressin and atrial natriuretic
      peptide on the development of brain edema in hyponatremic rats.
AB  - OBJECTIVE: Centrally released arginine vasopressin (AVP) and atrial natriuretic
      peptide (ANP) have been shown to participate in brain volume regulation. The aim
      of the present study was to evaluate the effects of centrally administered AVP
      and ANP on the time course of development of brain edema in vivo in hyponatremic
      rats, using diffusion-weighted magnetic resonance imaging. METHODS: We performed
      intracerebroventricular (ICV) administration of 120 microg AVP, 20 microg ANP, or
      physiological saline into the right lateral ventricle in 18 rats. Twenty-five
      minutes after the treatment, we induced systemic hyponatremia by the
      intraperitoneal administration of 140 mmol/L dextrose solution. Serial diffusion
      weighted imaging scans were obtained up to 96 minutes after the start of the
      hyponatremia. Changes in the brain extra-to intracellular volume fraction ratio
      were estimated as changes in the apparent diffusion coefficient (ADC). RESULTS:
      No change in the ADC was observed after the ICV injection of saline or AVP. The
      onset of hyponatremia induced a rapid and marked ADC reduction in both groups,
      indicating an increased intracellular space. However, the ADC decrease became
      significantly more pronounced in the ICV AVP group (83.3+/-4.7% of baseline
      level, mean +/- standard deviation) than in the saline group (93.7+/-3.3% of
      baseline, P < 0.001) after 78 minutes of hyponatremia. The ICV injection of ANP
      induced a prompt ADC increase to 111.5+/-10.0% (P < 0.05) of the baseline level,
      indicating a rapid reduction in the intracellular compartment. In the initial
      phase of hyponatremia, the ADC values in the ANP group were consistently higher
      than those in the saline group, decreasing finally to 86.9+/-9.6% after 96
      minutes of hyponatremia. CONCLUSION: Our findings demonstrate the opposite
      effects of AVP and ANP on the intracellular volume fraction of the brain during
      the development of cellular brain edema, with an immediate effect on ANP and a
      delayed effect on AVP. The results emphasize the direct effects of these hormones
      on the cellular volume regulatory mechanisms in the brain during the development
      of cerebral edema.

PMID- 11523683
TI  - Long-term activation of the glutamatergic system associated with N-methyl-D
      aspartate receptors after postischemic hypothermia in gerbils.
AB  - OBJECTIVE: The objective of this study was to investigate whether hypothermia
      would suppress secondary damage in the chronic postischemic stage, in terms of
      glutamate excitotoxicity. METHODS: Gerbils underwent 5 minutes of ischemia via
      bilateral common carotid artery occlusion. Seven groups were studied, as follows:
      1) ischemia without treatment group; 2) intraischemic hypothermia group; 3)
      postischemic hypothermia group (32 degrees C for 4 h); 4) MK-801 treatment group
      (2 mg/kg, every other day for 1 mo); 5) postischemic hypothermia with MK-801
      treatment for 1 week group (2 mg/kg, every other day); 6) postischemic
      hypothermia with MK-801 treatment for 1 month group (2 mg/kg, every other day);
      and 7) sham-treated control group. One month after ischemia, histological changes
      in hippocampal CA1 neurons (assessed using hematoxylin and eosin staining) and
      memory function (assessed using an eight-arm radial maze) were studied.
      Extracellular glutamate concentrations were monitored by microdialysis during
      ischemia and hypothermia. Staining of microglia was performed 1 week and 1 month
      after ischemia. RESULTS: MK-801 alone, postischemic hypothermia alone, and
      postischemic hypothermia with MK-801 treatment for 1 week failed to prevent
      ischemic neuronal damage and memory function decreases 1 month after the insult
      (P < 0.05 versus control). However, the postischemic hypothermia with MK-801
      treatment for 1 month group exhibited significant protective effects (not
      significant [P > 0.05] compared with the control group). Extracellular glutamate
      levels for the intraischemic hypothermia group were significantly low, compared
      with the postischemic hypothermia group. There was no microglial activation in
      the postischemic hypothermia at 1 week and 1 month after ischemia groups.
      CONCLUSION: Postischemic hypothermia and long-term intermittent administration of
      MK-801 demonstrated significant neuronal protection, indicating that long-term
      glutamatergic activation, with changes in N-methyl-D-aspartate receptors, plays a
      role in neuronal damage in the chronic postischemic stage.

PMID- 11523684
TI  - Focal intracranial infections due to Propionibacterium acnes: report of three
      cases.
AB  - OBJECTIVE AND IMPORTANCE: Except for its role in shunt infections,
      Propionibacterium acnes has been of little interest to neurosurgeons. The rarity
      and indolent nature of focal intracranial infections by P. acnes limit their
      recognition. Three cases of serious intracranial infection due to this organism
      are described. CLINCAL PRESENTATION: Three patients with histories of
      immunosuppression and neurosurgical procedures developed nonspecific, delayed
      presentations (5 wk to 5 yr after surgery) of intracranial infections. In two
      patients, radiological investigations showed enhancing lesions that were later
      found to be brain abscesses. A subdural empyema was found in the third patient.
      INTERVENTION: All three patients underwent surgical drainage of the purulent
      collections. P. acnes was isolated in each case, and each patient was treated
      with a 6-week course of intravenous penicillin. All three patients made good
      recoveries, and subsequent imaging showed no recurrence of the infectious
      collections. CONCLUSION: P. acnes is an indolent organism that may rarely cause
      severe intracranial infections. This organism should be suspected when an
      intracranial purulent collection is discovered in a patient with a history of
      neurosurgical procedures. Immunosuppressed patients may be susceptible to this
      otherwise benign organism. Surgical drainage and treatment with intravenous
      penicillin should be considered standard therapy.

PMID- 11523685
TI  - A neurocytoma and an associated lenticulostriate artery aneurysm presenting with
      intraventricular hemorrhage: case report.
AB  - OBJECTIVE AND IMPORTANCE: Hemorrhage associated with central neurocytoma has been
      described previously, but never in association with an aneurysm originating from
      a feeding artery. We present the first reported case of a central neurocytoma in
      a patient with intraventricular hemorrhage caused by rupture of an aneurysm on a
      lenticulostriate artery that supplied the tumor. CLINICAL PRESENTATION: A 35-year
      old man who presented with an intraventricular hemorrhage underwent magnetic
      resonance imaging and cerebral angiography that disclosed a right lateral
      intraventricular mass and a 7-mm fusiform aneurysm from a lateral
      lenticulostriate branch of the right middle cerebral artery. INTERVENTION: The
      patient underwent a contralateral transcallosal exploration and resection of the
      tumor, with excision of the adjacent lenticulostriate artery aneurysm.
      Pathological review demonstrated that the tumor was a neurocytoma. The aneurysm
      was discrete from the tumor but occurred on a vessel that supplied the tumor.
      CONCLUSION: Previous reports have demonstrated that intraventricular neurocytoma
      may present with tumor hemorrhage. In this case, an aneurysm separate and
      distinct from the tumor was the bleeding culprit, and the aneurysm was on an
      artery that fed into the tumor. Any such aneurysm must be identified and treated
      appropriately for therapy to be complete.

PMID- 11523686
TI  - Successful surgical relief of seizures associated with hamartoma of the floor of
      the fourth ventricle in children: report of two cases.
AB  - OBJECTIVE AND IMPORTANCE: To discuss the physiopathology and surgical handling of
      seizures due to hamartoma of the floor of the fourth ventricle in two children.
      CLINICAL PRESENTATION: Two girls aged 3 years at the time of their operations
      presented with seizures due to a lesion of the floor of the fourth ventricle. The
      seizures began within the first days of life and consisted of hemifacial
      contraction, then head deviation, blinking of the eyelids, and intermittent
      dysautonomic manifestations. The interictal neurological condition seemed normal
      in one patient and showed a slight development delay in the other. An ictal
      electroencephalogram showed slow waves in the posterior areas. A magnetic
      resonance imaging scan revealed a mass that remained unchanged on serial
      examinations bordering the fourth ventricle, with an isointense signal on T1
      weighted sequences and high-intensity signals on T2-weighted sequences without
      gadolinium enhancement. An ictal single-photon emission computed tomographic scan
      showed hyperperfusion in the lesion in both girls. INTERVENTION: The operation
      consisted of resection and disconnection of the lesion. An electrical recording
      was obtained in one patient during the operation while she was anesthetized; the
      recording, made by means of a depth electrode with five contacts inside the
      lesion, indicated that repetitive theta rhythmic discharges were present.
      Neuropathology was consistent with a hamartoma. In both girls, the seizures
      disappeared after their operations, and antiepileptic drugs were withdrawn
      (follow-up periods, 8 and 3 yr, respectively). CONCLUSION: Considering the
      results of single-photon emission computed tomography, the intralesional
      electrical record, and the relief of seizures after the operation, we postulate
      that the seizures arose from inside the lesion. This particular kind of
      noncortical seizure is similar to gelastic seizure due to hypothalamic hamartoma.

PMID- 11523687
TI  - Bilateral resective epilepsy surgery in a child with tuberous sclerosis: case
      report.
AB  - OBJECTIVE AND IMPORTANCE: Surgical intervention can reduce the burden of seizures
      in selected patients with tuberous sclerosis and medically refractory epilepsy.
      CLINICAL PRESENTATION: A child presented with tuberous sclerosis and severe
      epilepsy beginning in the first month of life and delayed development before 1
      year of age. Video-electroencephalographic monitoring at the age of 1 year
      revealed a left temporal seizure focus. Repeat videoelectroencephalography at 2
      years of age revealed a right posterior quadrant seizure focus. Bilateral
      subdural electrodes were placed, confirming independent seizure onsets from the
      right parietal area (overlying a tuber) and prominent interictal activity over
      the left superior temporal region. INTERVENTION: The right parietal focus was
      resected, and electrodes were maintained over the left temporal focus. After
      right parietal resection, ictal discharges were recorded over the left temporal
      region; a corticectomy was performed 2 days later. No tonicoclonic or complex
      partial seizures have occurred during a follow-up period of more than 24 months.
      Simple partial motor seizures involving the right foot have been reduced by more
      than 80%, and other simple partial seizures have been eliminated.
      Postoperatively, there has been marked improvement in the patient's cognitive and
      motor developmental status. CONCLUSION: In selected patients with bilateral
      seizure foci involving separate lobes, aggressive bilateral surgery can be safe
      and effective.

PMID- 11523688
TI  - Virtual movements activate primary sensorimotor areas in amputees: report of
      three cases.
AB  - OBJECTIVE: In our multidisciplinary pain clinic, three patients with amputated
      limbs and with surgical indications for chronic motor cortex stimulation for
      phantom limb pain were selected for their ability to voluntarily move the missing
      limb. The sensation of being able to move a missing limb at will occurs quite
      frequently among traumatic amputees, but the ability to control it sufficiently
      to perform a functional magnetic resonance imaging (fMRI) examination is more
      rarely encountered. We used motor fMRI to study these virtual movements. METHODS:
      In two patients with upper-limb amputations, movements of the stump, the normal
      hand, and the missing arm were studied. In a third patient with both legs
      amputated, movements of the stumps and of the missing feet were studied. The fMRI
      data were analyzed with the Statistical Parametric Map 96 software and
      reformatted for integration into anatomic slices. RESULTS: Virtual movements of
      the missing limbs produced contralateral primary sensorimotor cortex and central
      sulcus activations in the patients with upper-limb amputation. Interhemispheric
      and bilateral activations were found in the patient with both legs amputated.
      These activation areas were different from the stump activation areas.
      Additionally, the significance thresholds chosen to generate the activation maps
      in virtual movements (although individual) were globally the same as those used
      to detect motor activation in the normal side of the patients. CONCLUSION:
      Cortical areas devoted to the missing limb seem to persist for several years
      after amputation. The precentral activations found in our patients are in
      agreement with the statement that the neural mechanisms involved in the mental
      representation of an action and in its execution are the same. Data from fMRI can
      be used to evaluate phantom limb virtual movements and to study cortical
      reorganization phenomena that can appear with time or as a result of some
      therapies. In these patients, fMRI data may be useful in assisting the
      neurosurgeon in the placement of chronic motor cortex electrodes.

PMID- 11523689
TI  - M2/M2 side-to-side rescue anastomosis for accidental M2 trunk occlusion during
      middle cerebral artery aneurysm clipping: technical note.
AB  - OBJECTIVE: A technically feasible and rapid technique for revascularizing the
      main branches of the middle cerebral artery (MCA) is described. This technique is
      applied mainly when clipping of an MCA aneurysm is complicated and occlusion of
      the origin of an MCA main branch results. METHODS: M2/M2 side-to-side anastomosis
      was applied in two patients in whom unplanned M2 occlusion occurred during the
      course of complicated MCA aneurysm clipping. The first patient underwent an
      emergency procedure after temporoparietal intracerebral hemorrhage. Unilateral
      mydriasis precluded preoperative angiographic workup, and a complex large MCA
      aneurysm was found as the source of hemorrhage. Shaping of the aneurysm neck by
      bipolar coagulation and clipping resulted in accidental occlusion of the superior
      trunk, and patency could not be regained despite multiple clip corrections. The
      second patient had an unruptured multilobulated aneurysm 8 mm in maximum
      diameter. Continuity of the inferior trunk was lost during clipping because of a
      tear at the origin. In both instances, side-to-side anastomosis was placed
      approximately 15 mm from the bifurcation, where the MCA main trunks ran side by
      side for a length of approximately 5 mm. RESULTS: After intracerebral hemorrhage,
      the first patient recovered to a level of moderate disability within 2 months.
      Substantial hemiparesis and expressive dysphasia remained as sequelae of the
      intracerebral hemorrhage. Digital subtraction angiography 2 months after the
      emergency procedure confirmed patency of the side-to-side anastomosis. The second
      patient was neurologically intact after recovery from anesthesia. Before
      discharge from the hospital on postoperative Day 8, digital subtraction
      angiography confirmed patency of the anastomosis. CONCLUSION: The MCA main
      branches usually run in close proximity for a short segment at the bottleneck
      entrance to the insular cistern. M2/M2 side-to-side anastomosis at this site is a
      rapid and feasible mode of revascularization of an M2 trunk accidentally occluded
      during complicated MCA aneurysm clipping.

PMID- 11523690
TI  - Dural reconstruction with fascia, titanium mesh, and bone screws: technical note.
AB  - OBJECTIVE: After the resection of cranial base tumors, there may not be enough
      free dural margin left for reconstruction after involved bone and dura have been
      removed. In such a situation, dural reconstruction becomes a problem. We propose
      a new technique of dural closure in such cases. METHODS: A fascial graft is
      prepared from either fascia lata, abdominal fascia, pericranium, or temporal
      fascia and is trimmed to a size slightly larger than that of the dural defect.
      The fascial graft is placed over the dural defect and affixed to the underlying
      bone with a piece of titanium mesh, titanium screws, or both. The graft is then
      reinforced with fibrin glue. RESULTS: This method of dural reconstruction has
      been used in five patients with basal meningiomas. Three were in the petromastoid
      area, and two were in the planum-ethmoid area. None of these patients experienced
      postoperative cerebrospinal fluid leak, and none experienced any complications
      related to the reconstruction. CONCLUSION: This technique of dural reconstruction
      can be used in selected cases of basal tumors without enough free dural margin to
      sew into a fascial graft.

PMID- 11523691
TI  - Subfascial implantation of intrathecal baclofen pumps in children: technical
      note.
AB  - OBJECTIVE: Indwelling intrathecal drug delivery systems are becoming increasingly
      important as a method of neuromodulation within the nervous system. In
      particular, intrathecal baclofen therapy has shown efficacy and safety in the
      management of spasticity and dystonia in children. The most common complications
      leading to explantation of the pumps are skin breakdown and infection at the pump
      implantation site. The pediatric population poses particular challenges with
      regard to these complications because appropriate candidates for intrathecal
      baclofen therapy are often undernourished and thus have a dearth of soft tissue
      mass to cover a subcutaneously implanted baclofen pump. We report a technique of
      subfascial implantation that provides greater soft tissue coverage of the pump,
      thereby reducing the potential for skin breakdown and improving the cosmetic
      appearance of the implantation site. METHODS: Eighteen consecutively treated
      children (average age, 8 yr, 7 mo) with spasticity and/or dystonia underwent
      subfascial implantation of a baclofen pump. These children's mean weight of 42.9
      lb is less than the expected weight for a group of children in this age group,
      ranging from 4 years, 8 months, to 15 years, 7 months. In all patients, the pump
      was inserted into a pocket surgically constructed between the rectus abdominus
      and the external oblique muscles and the respective anterior fascial layers.
      RESULTS: At an average follow-up of 13.7 months, no infection or skin breakdown
      had occurred at the pump surgical site in any of the 18 patients. CONCLUSION: At
      this early follow-up, the subfascial implantation technique was associated with a
      reduced rate of local wound and pump infections and provided optimal cosmetic
      results as compared with that observed in retrospective cases.

PMID- 11523692
TI  - OHRP orders Johns Hopkins University to suspend human subjects research.

PMID- 11523693
TI  - Pressure on Bush builds as debate over stem cell research escalates.

PMID- 11523694
TI  - Matrix metalloproteinases: from biology to therapeutic strategies in
      cardiovascular disease.
AB  - In this comprehensive review of matrix remodeling, one central theme that bears
      re-emphasis is the extensivecross-talk and dynamic interactions that exist
      between terminally differentiated, postmitotic cells, proliferative cells, and
      the ECM of the cardiovascular system. The activities of MMPs and TIMPs constitute
      a well-orchestrated contest to maintain tissue integrity and homeostasis.
      Overexpression of MMPs tilts the balance in favor of irreversible tissue
      destruction of joints (eg, as in rheumatic disease), and efforts to curtail such
      errant pathways are ongoing (123). Thrombolytic therapy and percutaneous
      transluminal coronary angioplasty represent effective strategies for restoring
      antegrade flow in occluded vessels, but multiple factors preclude most patients
      with AMI from receiving either of these treatments. Tissue healing and remodeling
      is a process in which the biology of MMPs becomes universally applicable. Basic
      lessons from the biochemistry and enzymology of MMPs, combined with the
      mechanisms of gene expression, will undoubtedly impact the development of future
      therapies involving MMPs and their endogenous inhibitors. In addition, formidable
      challenges, ranging from bioavailability to tissue penetration and toxicity in
      animal models, face investigators using existing pharmacotherapeutics. For
      congenital diseases, such as Marfan syndrome, which primarily affects the
      connective tissue, future therapies may be targeted to the underlying
      pathobiology involving MMPs. Strategies aimed at correction of the genetic defect
      may be complemented by those to prevent or ameliorate fundamental imbalances in
      matrix turnover and deposition. The future challenge for cardiovascular medicine
      is to appropriately shift the pendulum, not to the exclusion of, but to the
      recognition of the dynamic interaction that exists between myocyte and nonmyocyte
      populations, which clearly affect the pathogenesis of many acquired and genetic
      disorders.

PMID- 11523695
TI  - Vascular expression of integrin-associated protein and thrombospondin increase
      after mechanical injury.
AB  - BACKGROUND: Integrin-associated protein (IAP) is a thrombospondin (TSP)-binding,
      Gi protein-coupled cell surface receptor. The vascular function of IAP has not
      been defined, and it is not known whether TSP and IAP are expressed at the same
      time in injured arteries. METHODS: Left brachial arteries of baboons were injured
      using balloon withdrawal technique. Arteries were harvested 1 week after injury,
      and immunohistochemistry and in situ hybridization were performed using standard
      techniques. Uninjured right brachial arteries served as a control. Proliferation
      studies were performed using cultured human aortic smooth muscle cells (SMC).
      RESULTS: We found significant IAP expression in the media and neointima 7 days
      after injury using BRIC-126, an immunoglobulin (Ig) G2b monoclonal antibody that
      recognizes IAP with high specificity. In contrast, IAP staining in the uninjured
      vessel was only observed in the endothelium. Concurrent with IAP expression, TSP
      mRNA and protein expression in the neointima and media was enhanced 1 week after
      injury. In cultured SMC, activation of IAP was sufficient to elicit a
      proliferative response. TSP-induced proliferation was inhibited by antibodies
      that block TSP binding to IAP and mimicked by 4N1K, a 10-amino acid peptide
      derived from the IAP binding site within the carboxyl terminus of TSP.
      CONCLUSIONS: Vascular expression of IAP and TSP increased after mechanical injury
      and activation of IAP elicited a proliferative response in cultured SMC. These
      findings support the hypothesis that IAP participates in vascular healing
      responses.

PMID- 11523696
TI  - Increased soluble P-selectin levels in hepatitis C virus-related chronic
      hepatitis: correlation with viral load.
AB  - BACKGROUND: Platelet functional abnormalities are commonly found in patients with
      chronic liver disease; however, their nature and clinical significance are still
      a matter of discussion. METHODS: Soluble P-selectin (sP-selectin, a marker of in
      vivo platelet activation) levels, lipid pattern, and clotting activity were
      investigated in 39 patients with histologically confirmed chronic C hepatitis.
      RESULTS: Serum factor VIIc (P < 0.01), total cholesterol (P < 0.005), high
      density lipoprotein (P < 0.001), and low density lipoprotein (P<0.05) levels were
      lower in patients compared with healthy subjects, whereas triglyceride and
      fibrinogen levels were similar in both groups. Platelet counts were lower in
      chronic hepatitis patients compared with controls (P < 0.0001), and approximately
      20% of patients had thrombocytopenia (platelet counts < 110 x 10(3)/microL).
      Platelet-associated immunoglobulin G (PAIgG) was present in 30.8% of patients.
      Plasma sP-selectin levels were higher in hepatitis C patients compared with
      controls (P < 0.0001), and significant differences were observed with respect to
      the Scheuer score (P < 0.01). The analysis of the distribution of plasma sP
      selectin showed the presence of higher levels in patients with low platelet
      counts compared with patients with normal platelet counts and controls (P <
      0.0001); moreover, sP-selectin levels did not correlate with the presence of
      PAIgG. On the other hand, sP-selectin levels directly correlated with serum
      hepatitis C virus (HCV)-RNA (P < 0.05) and inversely correlated with platelet
      count, blood lipids, and factor VIIc. CONCLUSIONS: The results obtained in this
      study support the hypothesis that HCV infection might be directly responsible for
      a condition of in vivo platelet activation in patients with chronic C hepatitis.

PMID- 11523698
TI  - Distribution and mRNA expression of insulin-like growth factor system in
      pulmonary lymphangioleiomyomatosis.
AB  - BACKGROUND: Insulin-like growth factors (IGF-1 and IGF-2), the IGF-1 receptor
      (IGF-1R), and IGF-binding proteins (IGFBPs) are involved in normal pulmonary
      development and in the pathogenesis of smooth muscle cell tumors. METHODS: To
      evaluate the role of the IGF system in lymphangioleiomyomatosis (LAM), we used
      immunohistochemical and in situ hybridization techniques to characterize the
      expression of IGF-1, IGF-2, IGF-1R, and IGFBP-2, -4, -5, and -6 in lung tissue
      from 18 LAM patients. RESULTS: IGF-1, ICGF-2, IGF-1R, IGFBP-1, IGFBP-2, IGFBP-4,
      IGFBP-5, and IGFBP-6 were expressed by LAM cells. Reactivity and mRNA expression
      for IGF-2 were observed in LAM cells and resembled that found in normal smooth
      muscle cells during pulmonary development as well as in smooth muscle cell
      tumors. IGFBP-2, IGFBP-4, and IGFBP-6 were associated with spindle-shaped LAM
      cells, whereas IGFBP-5 was associated mainly with epithelioid LAM cells.
      CONCLUSIONS: These findings suggest that the IGFBPs modulate the effects of the
      IGFs on LAM cells. Thus, the patterns of localization and expression of
      components of the IGF system in LAM strongly suggest that these agents are
      involved in the proliferation of LAM cells.

PMID- 11523699
TI  - Susceptibility to cytomegalovirus infection may be dependent on the cytokine
      response to the virus.
AB  - BACKGROUND: Cytomegalovirus (CMV) infection is an important cause of morbidity
      and mortality in an immunocompromised host. Pulmonary infection with CMV results
      in an inflammatory response, which includes the local production of cytokines.
      Cytokine production stimulated by CMV infection serves to activate a series of
      immunologic responses involved in viral clearance. Previous work has demonstrated
      that different mouse strains express variable sensitivity to CMV infection.
      METHODS: Using mouse strains that express sensitive (BALB/cj) and resistant
      (C57BL/6) CMV phenotypes, we asked whether the differences in susceptibility to
      infection were caused by differences in pulmonary cytokine production after
      intraperitoneal infection with CMV. RESULTS: C57 mice demonstrated a higher total
      bronchoalveolar lavage (BAL) and BAL lymphocyte count at 3 and 7 days after
      intraperitoneal infection compared with BALB mice. There were no differences in
      BAL cytokine production; however, we were able to demonstrate differences in CMV
      DNA load in the lungs of BALB mice compared with that of C57 mice. In addition,
      there appeared to be increased whole-lung production of the TH2 cytokine IL-10 in
      the BALB mice versus the C57 mice. CONCLUSIONS: This observation suggests that
      the genetic susceptibility to CMV infection may, in part, be regulated by
      differences in cytokines production within the local environment.

PMID- 11523697
TI  - Magnitude of peroxisome proliferator-activated receptor-gamma activation is
      associated with important and seemingly opposite biological responses in breast
      cancer cells.
AB  - BACKGROUND: The nuclear receptor peroxisome proliferator-activated receptor-gamma
      (PPARgamma) has become a potential target for the prevention and treatment of
      breast cancer. However, recent in vitro and in vivo studies have raised the
      question of whether activation of PPARgamma leads to the promotion or reduction
      of tumor formation. Studies using several cancer cell lines, animal models, and a
      variety of PPARgamma agonists have shown discordant results, including changes in
      cellular proliferation, differentiation, and apoptosis of cancer cells and
      tumors. METHODS: We studied the effects of low-, moderate-, and high-dose
      treatment of the PPARgamma ligands 15-deoxy-delta1214 prostaglandin J2 (15dPGJ2)
      and troglitazone (TGZ) on parameters of cell growth, differentiation, and
      apoptosis in the epithelial breast cancer cell line MDA-MB-231. RESULTS: The
      biologic effects of these compounds depend largely on ligand concentration and
      the degree of PPARgamma activation. For example, low concentrations of 15dPGJ2
      (<2.5 microM) and TGZ (<5 microM) increased cellular proliferation, but
      concentrations of 15dPGJ2 > or = 10 microM and of TGZ at 100 microM blocked cell
      growth. TGZ (100 microM) slowed cell cycle progression, and 15dPGJ2 (10 microM)
      caused an S-phase arrest in the cell cycle and induced morphological
      characteristics consistent with apoptosis. Expression of CD36, a marker of
      differentiation in these cells, was induced by 2.5 microM 15dPGJ2 or 5 to 100
      microM TGZ. However, higher concentrations of 15dPGJ2 did not alter CD36
      expression. Transcriptional activation studies demonstrated that 15dPGJ2 is a
      more potent PPARgamma ligand than TGZ. Regardless of the ligand used, though, low
      transcriptional activation correlated with an increased cellular proliferation,
      whereas higher levels of activation correlated with cell cycle arrest and
      apoptosis. CONCLUSIONS: PPARgamma activation induces several important and
      seemingly opposite changes in neoplastic cells, depending on the magnitude of
      PPARgamma activation. These data may explain, at least in part, some of the
      discordant results previously reported.

PMID- 11523700
TI  - Tacrolimus and cyclosporine A inhibit allostimulatory capacity and cytokine
      production of human myeloid dendritic cells.
AB  - Myeloid dendritic cells (DCs) are pivotal in the recognition of alloantigens and,
      therefore, in the induction of allograft rejection. Induction of alloreactive T
      cell proliferation by myeloid DCs depends on the maturation of DCs, the
      expression of costimulatory molecules, and the cytokine environment. This study
      investigated the effects of tacrolimus and cyclosporine A (CsA) on DC maturation
      and allostimulatory capacity. Myeloid DCs were propagated from normal blood
      monocytes with interleukin (IL) 4 and GM-CSF for 7 days in the presence or
      absence of tacrolimus (FK506; 10 nM) or CsA (1 microg/mL). Exposure of DCs during
      maturation to tacrolimus or CsA resulted in no significant change in the
      expression of DC phenotypic markers, including CD80, CD86, and HLA Class I and II
      antigens determined by flow cytometry. T cell proliferation in one-way, mixed
      leukocyte reaction experiments revealed a decreased allostimulatory capacity of
      DCs that matured in the presence of tacrolimus or CsA compared with untreated
      controls (P<0.02). Production of inflammatory cytokines, tumor necrosis factor
      alpha (P<0.04) and IL-12 (P<0.04) in response to lipopolysaccharide (1 microg/mL)
      or staphylococcal enterotoxin B (1 microg/mL) induction was significantly reduced
      in DCs exposed to tacrolimus or CsA during maturation. In contrast, production of
      the immuninhibitory cytokine IL-10 was not decreased in tacrolimus- or CsA
      treated DCs. These results suggest that tacrolimus and CsA inhibit the
      allostimulatory capacity of in vitro-generated myeloid DCs without significant
      effects on DC phenotypic maturation. Decreased production of IL-12 and tumor
      necrosis factor alpha, but not of IL-10, is likely to contribute to the impaired
      accessory-cell function of tacrolimus- and CsA-treated DCs. Thus, tacrolimus and
      CsA can inhibit recognition of alloantigens by decreasing the accessory-cell
      capacity of monocyte-derived myeloid DCs.

PMID- 11523701
TI  - Early onset of lipid peroxidation after human traumatic brain injury: a fatal
      limitation for the free radical scavenger pharmacological therapy?
AB  - BACKGROUND: On the basis of the contradiction between data on experimental head
      trauma showing oxidative stress-mediated cerebral tissue damage and failure of
      the majority of clinical trials using free radical scavenger drugs, we monitored
      the time-course changes of malondialdehyde (MDA, an index of cell lipid
      peroxidation), ascorbate, and dephosphorylated ATP catabolites in cerebrospinal
      fluid (CSF) of traumatic brain-injured patients. METHODS: CSF samples were
      obtained from 20 consecutive patients suffering from severe brain injury. All
      patients were comatose, with a Glasgow Coma Scale on admission of 6 +/- 1. The
      first CSF sample for each patient was collected within a mean value of 2.95 hours
      from trauma (SD=1.98), after the insertion of a ventriculostomy catheter for the
      continuous monitoring of intracranial pressure. During the next 48 hours, CSF was
      withdrawn from each patient once every 6 hours. All samples were analyzed by an
      ion-pairing high-performance liquid chromatographic method for the simultaneous
      determination of MDA, ascorbic acid, hypoxanthine, xanthine, uric acid, inosine,
      and adenosine. RESULTS: In comparison with values recorded in 10 herniated-lumbar
      disk, noncerebral control patients, data showed that all CSF samples of brain
      injured patients had high values (0.226 micromol/L; SD=0.196) of MDA
      (undetectable in samples of control patients) and decreased ascorbate levels
      (96.25 micromol/L; SD=31.74), already at the time of first withdrawal at the time
      of hospital admission. MDA was almost constant in the next two withdrawals and
      tended to decrease thereafter, although 48 hours after hospital admission, a mean
      level of 0.072 micromol/L CSF (SD=0.026) was still recorded. The ascorbate level
      was normalized 42 hours after hospital admission. Changes in the CSF values of
      ATP degradation products (oxypurines and nucleosides) suggested a dramatic
      alteration of neuronal energy metabolism after traumatic brain injury.
      CONCLUSIONS: On the whole, these data demonstrate the early onset of oxygen
      radical-mediated oxidative stress, proposing a valid explanation for the failure
      of clinical trials based on the administration of oxygen free radical scavenger
      drugs and suggesting a possible rationale for testing the efficacy of lipid
      peroxidation "chain breakers" in future clinical trials.

PMID- 11523702
TI  - Epistatic quantitative trait loci for alcohol preference in mice.
AB  - Alcohol consumption is a complex trait, responding to the influence of various
      genes and environmental influences acting in a quantitative fashion. Various
      studies in alcohol consumption processes have identified quantitative trait locus
      (QTL) regions across the mouse genome that appear to contribute to this
      phenotype. The purpose of this study was to examine the influence of interactions
      between alleles at different loci, a phenomenon known as epistasis, on previously
      identified QTLs for alcohol consumption in mice. A multiple regression model was
      developed and applied to test for the significance of the interaction between two
      QTLs and to quantify this interaction. Our results indicate the presence of
      epistasis between loci on mouse chromosomes 2 and 3 accounting for 7-8% of the
      variation in alcohol preference, respectively.

PMID- 11523704
TI  - Mapping quantitative trait loci for circadian behavioral rhythms in SMXA
      recombinant inbred strains.
AB  - SM/J and A/J inbred strain of mice have different characteristics in circadian
      behaviors such as free-running period (tau), phase relationship (psi) between
      light-dark cycles and activity rhythms, and amount of wheel-running activity. To
      determine the genes which affect these behaviors, a quantitative trait locus
      (QTL) analysis using SMXA recombinant inbred strains derived from SM/J and A/J
      mice was performed. Concerning tau, two regions on chromosomes (Chrs) 7 and 18
      surpassed the genome-wide suggestive level. As for psi, one suggestive QTL was
      detected on Chr 7. The QTLs which affect daily activity counts under light-dark
      cycles and constant darkness were mapped to the same chromosomal regions on Chrs
      1 and 17, respectively. The provisional QTLs detected in the present study might
      be useful for understanding the complex mechanism regulating circadian behaviors.

PMID- 11523703
TI  - Behavioral profiles of genetically selected aggressive and nonaggressive male
      wild house mice in two anxiety tests.
AB  - Artificially selected aggressive (SAL) and non-aggressive (LAL) male house mice
      were tested in a hexagonal tunnel maze and light-dark preference (LD) box to
      determine if the bidirectional selection for aggressive behavior leads to a
      coselection for different levels of trait anxiety. The tunnel maze consists of an
      open, brightly lit central arena surrounded by a complex system of
      interconnecting tunnels. As in the LD box, animals which spend less time and are
      less active in the brightly illuminated section of the maze are considered to
      have higher anxiety levels. In the tunnel maze, the LAL mice showed more
      exploration and spent more time in the central arena than the SAL animals, but
      only during the final 2 min of the 6-min test. This reduced preference for the
      central arena was not due to general inactivity or a failure of the SAL to find
      the central arena and indicates a higher level of state anxiety in the aggressive
      animals. In contrast, no "anxiety-like" differences were found in the LD box,
      either for the percentage of time spent in the light compartment or for the
      number of crossings. SAL males actually showed higher levels of moving and
      rearing, and lower levels of freezing, than did LAL males.

PMID- 11523705
TI  - Multivariate models of mixed assortment: phenotypic assortment and social
      homogamy for education and fluid ability.
AB  - Phenotypic assortment is assumed to be the principal mechanism of spouse
      similarity in most biometrical studies. Other assortment mechanisms, such as
      social homogamy, may be plausible. Two models are presented that consider
      phenotypic assortment and social homogamy simultaneously (i.e., mixed
      assortment), where selective associations between social background factors
      (Model I) versus selective associations between total environments (Model II)
      distinguish the models. A series of illustrative analyses was undertaken for
      education and fluid ability available on a sample of 116 Swedish twin pairs and
      their spouses. On the basis of several fit criteria Model I was preferred over
      Model II. Both social homogamy and phenotypic assortment may contribute to spouse
      similarity for educational attainment and fluid ability. Furthermore, spouse
      similarity for fluid ability may arise indirectly from social homogamy and
      phenotypic assortment for educational attainment. Power analyses indicated
      greater observed power for Model I than Model II. Additional power analyses
      indicated that considerably more twin-spouse sets would be needed for Model II
      than Model I, to resolve social homogamy and phenotypic assortment. Effects of
      misspecification of mechanisms of spouse similarity are also briefly discussed.

PMID- 11523706
TI  - Genetic and environmental contributions to the association between body height
      and educational attainment: a study of adult Finnish twins.
AB  - The nature of the association between body height and educational attainment
      found in previous studies remains to be clarified. The aim of this study was to
      examine factors contributing to this association by using a large Finnish twin
      data set (8798 adult twin pairs) gathered by questionnaire in 1981. A bivariate
      twin analysis was used to determine whether the genetic and environmental factors
      behind body height and educational attainment correlate with each other. A high
      heritability was found for body height (h2 = 0.78 in men and h2 = 0.75 in women),
      and a moderate heritability for education (h2 = 0.47 and h2 = 0.43,
      respectively). Shared environmental effects were also important in body height
      (c2 = 0.12 in men and c2 = 0.11 in women) and education (c2 = 0.36 and c2 = 0.43,
      respectively). A high correlation (r(c) = 0.77 in men, r(c) = 0.58 in women) of
      shared environmental factors education and body height, and weaker correlations
      (r = 0.11 and r = 0.08, respectively) of unshared environmental factors were
      found. The correlation of genetic factors between these two characteristics was
      not statistically significant. The results suggest that the association between
      body height and education is due mainly to nongenetic family factors.

PMID- 11523707
TI  - Parental education and child's verbal IQ in adoptive and biological families in
      the National Longitudinal Study of Adolescent Health.
AB  - This study compared adoptive children and matched, biological children to
      estimate the genetic and environmental effect of years of mothers' and fathers'
      education on children's verbal intelligence (VIQ), as assessed by knowledge of
      vocabulary words. Adoptive and biological adolescent children in the National
      Longitudinal Study of Adolescent Health (Add Health) were matched for sex, age,
      parental education, and ethnicity. The adolescents all resided with two parents.
      Structural equation modeling was employed using Mx to estimate the genetic and
      transmissible environmental components of the correlation between parental
      education and children's VIQ. The mother-child and father-child correlations in
      biological families were .41 and .36, respectively, vs .16 and .18 in adoptive
      families. As suggested by these correlations, both genetic and shared
      environmental influences were statistically significant in the Mx models. We
      conclude that parental education exerts a modest shared environmental effect,
      explaining no more than 3 to 4% of the variation in verbal intelligence.

PMID- 11523708
TI  - Pseudoaneurysms of the femoral artery: recommendation for a method of repair.
AB  - PURPOSE: Formation of an anastomotic aneurysm in the femoral artery is one of the
      major complications after femoral artery surgery. The aim of this study was to
      assess the method of repair of femoral anastomotic aneurysms and their outcome in
      a District General Hospital. METHODS: A retrospective consecutive cohort of
      anastomotic femoral aneurysms, operated between 1977 and 1998, were studied.
      RESULTS: Twelve patients with a total of 19 pseudoaneurysms were treated. Five of
      the aneurysms were repaired using a vein patch and two had re-suturing of the
      anastomosis. Twelve aneurysms were repaired with complete revision of the
      anastomoses using interposition grafts. There were no recurrences in the
      interposition graft group whilst two recurred in the seven aneurysms repaired
      using re-suturing/vein patch. CONCLUSION: Interposition grafting would appear to
      be the method of choice for repair of femoral pseudoaneurysms as the outcome was
      better than that with re-suturing or using a patch closure technique.

PMID- 11523709
TI  - Treatment and outcome of cystosarcoma phyllodes in Brunei: a 13-year experience.
AB  - Cystosarcoma phyllodes is a rare tumour of the breast whose clinical behaviour
      does not correlate well with histological findings. The optimal treatment of this
      tumour remains controversial. A retrospective study on the treatment and outcome
      of women diagnosed with cystosarcoma phyllodes between 1986 and 1998 in Brunei
      was undertaken. Twenty-seven women were diagnosed over the 13-year study period.
      Follow-up was complete in 26 cases. The mean age at diagnosis was 35 years. There
      were 19 (73%) histologically benign lesions, 3 (12%) borderline lesions and 4
      (15%) malignant lesions. The mean follow-up period was 37 months. Four patients
      (16%) had recurrences after surgery (1 benign, 1 borderline and 2 malignant
      lesions). Mean time to recurrence was 9 months. Breast-conserving surgery with
      adequate resection margin is advocated in benign and borderline lesions. For
      malignant lesions, simple mastectomy without routine axillary dissection is
      recommended. More research is required to determine the role of adjuvant
      chemotherapy and radiotherapy in the management of malignant cystosarcoma
      phyllodes [corrected].

PMID- 11523710
TI  - Island pectoralis major myocutaneous flap for pharyngo-oesophageal strictures
      prior to oesphagocoloplasty.
AB  - Pharyngo-oesophageal strictures are not uncommon in corrosive injuries either
      alone or in association with dense strictures further down the oesophagus.
      Strictures at the pharyngo-oesophageal junction require preliminary correction
      prior to oesophageal bypass since surgical bypass to the pharynx above the
      cricopharyngeal junction is associated with risk of aspiration. A one stage
      island pectoralis major myocutaneous flap has been used in four patients who had
      a non-dilatable dense cricopharyngeal stricture leading to a segment of near
      normal oesophagus followed by dense stricturing of the thoracic oesophagus. This
      procedure was followed by oesphagocolic bypass at a second stage from the
      cervical oesophagus to the stomach. The preliminary pectoralis major flap
      correction avoids problems such as aspiration or choking associated with pharyngo
      colic anastomosis for oesophageal bypass. All four patients had uncomplicated
      healing. Post-operative endoscopy showed easy passage through the cricopharynx
      with a dilated cervical oesophagus partly lined by skin. Normal swallowing was
      restored by a second stage oesphago-colic bypass 6 weeks after the pectoralis
      major flap repair in two patients while the other two are awaiting the second
      stage. Island pectoralis major myocutaneous flap is simple, has a dependable
      vascularity and offers one stage correction for isolated cricopharyngeal
      corrosive stricture. It can also be used prior to oesophagocolic bypass in
      patients who have further strictures in the thoracic oesophagus.

PMID- 11523711
TI  - Management of simple renal cysts in children.
AB  - Simple renal cysts are uncommon in children and their presentation and management
      has changed with increasing use of ultrasound scans. The aim of this study was to
      review our experience and highlight some peculiarities in diagnosis and
      management of these cases. Eight cases were diagnosed and two symptomatic cases
      underwent aspiration under ultrasound guidance; one case recurred and required re
      aspiration. Differentiation of simple renal cysts from other cystic lesions of
      the kidney, aspiration of symptomatic cysts and the importance of long-term
      follow-up are discussed.

PMID- 11523712
TI  - The effect of sentinel lymph node biopsy on the Nottingham Prognostic Index in
      breast cancer patients.
AB  - The Nottingham Prognostic Index (NPI) is a prognostic variable suitable for the
      stratification of breast cancer patients for adjuvant systemic treatment. The
      impact of sentinel node biopsy (SNB) and of the assessment of nodal involvement
      was evaluated in 136 successful SNB procedures completed by axillary dissection
      (AD). The three strategies assessed included SNB and AD in all cases, AD only in
      SN-positive cases, and AD only if the SN contained macrometastases. Isolated
      tumour cells in lymph nodes were regarded either as metastases or as negative
      findings. The success rate and accuracy of SNB were 90% and 96%, respectively.
      The NPI was influenced by variations in the surgical staging strategy and the
      definition of nodal involvement, in at most, five patients. Adjuvant systemic
      treatment, indicated on the basis of the NPI is less influenced by staging
      strategies and definitions of metastases than that given on the basis of nodal
      status alone.

PMID- 11523713
TI  - Career advice--the role of appraisal.
AB  - The purpose of this article is to discuss the benefits of and to illustrate a
      framework for appraisal. The place of career advice in this process is mentioned,
      as is a brief discussion on assessment. From the point of view of the individual
      doctor, information to help him/her choose an appropriate career path should be
      readily available. It is more likely that a doctor will perform well throughout
      their career if in a career or occupation that suits them.

PMID- 11523714
TI  - Risk group-based management of differentiated thyroid carcinoma.
AB  - A number of controversies exist in the treatment of differentiated thyroid
      carcinoma with respect to the extent of surgery, use of radioactive iodine and
      post-operative thyroxine suppression. Recent recognition of prognostic factors
      has helped to assign patients, based on their risk profile, as being at high risk
      of developing recurrence. This has facilitated the development of a selective
      approach to therapy, thus, avoiding unnecessary treatment and reducing morbidity
      without compromising treatment outcome. This review attempts to evaluate the
      current concepts of management of differentiated thyroid carcinoma in the light
      of these new developments.

PMID- 11523715
TI  - James Wardrop (1782-1869): from Whitburn to Windsor Castle.
AB  - The medical career of a Scottish doctor, James Wardrop, in the 19th century is
      described. An early interest in the developing science of Pathology in the Royal
      College of Surgeons of Edinburgh was expanded further when he moved to London,
      due to financial needs. Despite being outside the London teaching hospital scene,
      he continued to publish and teach in the private schools of the time. His
      interest in ophthalmology led him to describe what we now know as retinoblastoma,
      with recommendation for treatment. He also described sympathetic ophthalmitis and
      performed paracentesis in acute angle-closure glaucoma. He became surgeon to the
      Prince of Wales, later King George IV, but his criticism of other medical men at
      court led to his exclusion from the King at the scene of his death. He owned a
      notable collection of pictures and presented two of them to the National Gallery
      of Scotland on its foundation in 1850. In recent years, his work has been
      recognised by leading ophthalmologists, particularly in the USA. The Library of
      the Royal College of Surgeons of Edinburgh contains several of his works, and his
      portrait hangs in the College.

PMID- 11523716
TI  - Combined treatment of a proliferative peri-orbital haemangioma with a tuneable
      dye laser and intra-lesional steroids to prevent deprivation amblyopia.
AB  - Rapidly proliferating haemangiomas of the face may obscure vision with the
      development of deprivation amblyopia. Early intervention is required to prevent
      complications. We present a case successfully treated with a combination of
      pulsed dye laser and intralesional steroid injection. The current management of
      haemangiomas is reviewed.

PMID- 11523717
TI  - Aquaporins and the surgeon: cautionary tales.
AB  - Nephrogenic diabetes insipidus (NDI) presents an uncommon but formidable clinical
      challenge in the surgical patient. Two recent cases of NDI with differing
      aetiology are presented. These cases and a review of the literature illustrate
      well the diagnosis, fluid and electrolyte imbalances seen and the strategy of
      treatment required in the post-operative setting. The central role of the
      recently discovered aquaporin channels in this condition is briefly outlined.
      Nephrogenic diabetes insipidus has a diverse aetiology and many of the hazards of
      the condition are peculiar to the surgical setting. The importance of management
      in a high dependency environment is highlighted.

PMID- 11523718
TI  - Surgical treatment of a tomaculous neuropathy.
AB  - Compressive neuropathy of the ulnar nerve at the elbow is the second most common
      nerve entrapment in the upper limb. Eight possible anatomical points of
      constriction have been identified. The most common constriction being the
      intermuscular septum proximally or between the two heads of the flexor carpi
      ulnaris in the cubital canal distally. Surgical release is successful in 80-90%
      of cases. Certain rare genetic conditions can predispose susceptible peripheral
      nerves to similar compressive neuropathies but there is no literature on surgical
      treatment of such patients. We present a case of hereditary neuropathy with
      liability to pressure palsy (HNPP) often known as 'tomaculous' neuropathy, in a
      patient with ulnar nerve symptoms who underwent a surgical release.

PMID- 11523719
TI  - Near total transection of the trachea following percutaneous dilatational
      tracheostomy.
AB  - The bedside procedure of percutaneous dilatational tracheostomy (PDT) in the
      intensive care unit continues to gain popularity. Percutaneous dilatational
      tracheostomy is recommended as simple, safe and cost-effective. The procedure can
      be associated with serious life-threatening complications. We report a case of
      near total transection of the trachea following PDT.

PMID- 11523720
TI  - Talc serodesis--report of four cases.
AB  - Talc is a known stimulator of fibrosis in biological systems. We present four
      cases in which instillation of talc in to serous cavities have produced
      obliteration of these cavities. No side-effects were noted.

PMID- 11523721
TI  - Post-partum ovarian vein thrombosis.
AB  - Post-partum ovarian vein thrombosis (POVT) is uncommon, but the true incidence is
      not known. Ninety per cent of cases present as right iliac fossa pain within 10
      days of delivery. Anti-coagulation and intravenous antibiotics are the mainstay
      of treatment. We report three cases that were referred to our unit. These cases
      illustrate the difficulty in the clinical diagnosis of POVT and highlight the
      importance of its inclusion in the differential diagnoses of an acute abdomen in
      post-partum patients. POVT can be accurately diagnosed by appropriate noninvasive
      investigations and a laparotomy avoided.

PMID- 11523722
TI  - Fireworks injury: temporal bone penetration and a wooden intra-cranial foreign
      body.
AB  - We describe a case of a teenager sitting in a car, who was struck by a fireworks
      missile. The unusual presentation of a large wooden foreign body penetrating
      through the temporal bone and lodging in the brain is detailed. The management is
      discussed.

PMID- 11523723
TI  - Measures of exposure versus measures of rate and extent of absorption.
AB  - Regulatory assessment of bioavailability and bioequivalence in the US frequently
      relies on measures of rate and extent of absorption. Rate of absorption is not
      only difficult to measure but also bears little clinical relevance. This paper
      proposes that measures of bioavailability and bioequivalence for drugs that
      achieve their therapeutic effects after entry into the systemic circulation are
      best expressed in terms of early [partial area under the concentration-time curve
      (AUC)], peak plasma or serum drug concentration and total AUC exposure for a
      plasma or serum concentration-time profile. With suitable documentation, these
      systemic exposure measures can be related to efficacy and tolerability outcomes.
      The early measure is recommended for an immediate release drug product where a
      better control of drug absorption is needed, for example to ensure rapid onset of
      a therapeutic effect or to avoid an adverse reaction from a fast input rate. The
      3 systemic exposure measures for bioavailability and bioequivalence studies can
      provide critical links between product quality and clinical outcome and thereby
      reduce the current emphasis on rate of absorption.

PMID- 11523724
TI  - Clinical pharmacokinetics of sirolimus.
AB  - Sirolimus (previously known as rapamycin), a macrocyclic lactone, is a potent
      immunosuppressive agent. Sirolimus was recently approved by the US Food and Drug
      Administration, on the basis of 2 large, double-blind, prospective clinical
      trials, for use in kidney transplant recipients at a fixed dosage of 2 or 5
      mg/day in addition to full dosages of cyclosporin and prednisone. However,
      despite the fixed dosage regimens used in these pivotal trials, pharmacokinetic
      and clinical data show that sirolimus is a critical-dose drug requiring
      therapeutic drug monitoring to minimise drug-related toxicities and maximise
      efficacy. Assays using high performance liquid chromatography coupled to mass
      spectrometry, although cumbersome, are the gold standard for evaluating other
      commonly used assays, such as liquid chromatography with ultraviolet detection,
      radioreceptor assay and microparticle enzyme immunoassay. Sirolimus is available
      in oral solution and tablet form. It has poor oral absorption and distributes
      widely in tissues, displaying not only a wide inter- and intrapatient variability
      in drug clearance, but also less than optimal correlations between whole blood
      concentrations and drug dose, demographic features or patient characteristics.
      Furthermore, the critical role of the cytochrome P450 3A4 system for sirolimus
      biotransformation leads to extensive drug-drug interactions, among which are
      increases in cyclosporin concentrations. Thus, sirolimus is now being used to
      reduce or eliminate exposure to cyclosporin or corticosteroids. The long
      elimination half-life of sirolimus necessitates a loading dose but allows once
      daily administration, which is more convenient and thereby could help to improve
      patient compliance. This review emphasises the importance of blood concentration
      monitoring in optimising the use of sirolimus. The excellent correlation between
      steady-state trough concentration (at least 4 days after inception of, or change
      in, therapy) and area under the concentration-time curve makes the former a
      simple and reliable index for monitoring sirolimus exposure. Target trough
      concentration ranges depend on the concomitant immunosuppressive regimen, but a
      range of 5 to 15 microg/L is appropriate if cyclosporin is being used at trough
      concentrations of 75 to 150 microg/L. Weekly monitoring is recommended for the
      first month and bi-weekly for the next month; thereafter,concentration
      measurements are necessary only if warranted clinically.

PMID- 11523726
TI  - Drug interactions with irbesartan.
AB  - Irbesartan is an angiotensin II receptor antagonist indicated for the treatment
      of patients with hypertension. Although irbesartan does not require
      biotransformation for its pharmacological activity, it does undergo metabolism
      via the cytochrome P450 (CYP) 2C9 isoenzyme and negligible metabolism by the
      CYP3A4 isoenzyme. The long term treatment of patients with hypertension is
      generally required for effective management of the disease, and the use of
      concurrent medications is usually inevitable. This paper reviews the drug and
      food interaction trials involving irbesartan that have been conducted to date.
      Based on the available literature, no significant interactions have been
      identified between irbesartan and hydrochlorothiazide, nifedipine, simvastatin,
      tolbutamide, warfarin, magnesium and aluminum hydroxides, digoxin or food.
      Fluconazole did increase the steady-state peak plasma concentration (by 19%) and
      area under the concentration-time curve (by 63%) of irbesartan, but these
      increases are not likely to be clinically significant. In summary, irbesartan has
      demonstrated minimal potential for drug or food interactions in trials conducted
      to date.

PMID- 11523725
TI  - Pharmacogenetics of warfarin elimination and its clinical implications.
AB  - Warfarin is one of the most widely prescribed oral anticoagulants. However,
      optimal use of the drug has been hampered by its >10-fold interpatient
      variability in the doses required to attain therapeutic responses.
      Pharmacogenetic polymorphism of cytochrome P450 (CYP) may be associated with
      impaired elimination of warfarin and exaggerated anticoagulatory responses to the
      drug in certain patients. Clinically available warfarin is a racemic mixture of
      (R)- and (S)-warfarin, and the (S)-enantiomer has 3 to 5 times greater
      anticoagulation potency than its optical congener. Both enantiomers are
      eliminated extensively via hepatic metabolism with low clearance relative to
      hepatic blood flow. CYP2C9 is almost exclusively responsible for the metabolism
      of the pharmacologically more active (S)-enantiomer. Several human allelic
      variants of CYP2C9 have been cloned, designated as CYP2C9*1 (reference sequence
      or wild-type allele), CYP2C9*2, CYP2C9*3 and CYP2C9*4, respectively. The allelic
      frequencies for these variants differ considerably among different ethnic
      populations. Caucasians appear to carry the CYP 2C9*2 (8 to 20%) and CYP2C9*3 (6
      to 10%) variants more frequently than do Asians (0% and 2 to 5%, respectively).
      The metabolic activities of the CYP2C9 variants have been investigated in vitro.
      The catalytic activity of CYP2C9*3 expressed from cDNA was significantly less
      than that of CYP2C9*1. Human liver microsomes obtained from individuals
      heterozygous for CYP2C9*3 showed significantly reduced (S)-warfarin 7
      hydroxylation as compared with those obtained from individuals genotyped as
      CYP2C9*1. The influence of the CYP2C9*3 allele on the in vivo pharmacokinetics of
      (S)-warfarin has been studied in Japanese patients. Patients with the homozygous
      CYP2C9*3 genotype, as well as those with the heterozygous CYP2C9*1/*3 genotype,
      had significantly reduced clearance of (S)-warfarin (by 90 and 60%, respectively)
      compared with those with homozygous CYP2C9*1. The maintenance dosages of warfarin
      required in Japanese patients with heterozygous and homozygous CYP2C9*3 mutations
      were significantly lower than those in patients with CYP2C9*1/*1. In addition,
      86% of British patients exhibiting adequate therapeutic responses with lower
      maintenance dosages of warfarin (<1.5 mg/day) had either the CYP2C9*2 or CYP2C9*3
      mutation singly or in combination, whereas only 38% of randomly selected patients
      receiving warfarin carried the corresponding mutations. Furthermore, the former
      group showed more frequent episodes of major bleeding associated with warfarin
      therapy. These data indicate that the CYP2C9*3 allele may be associated with
      retarded elimination of (S)-warfarin and the resulting clinical effects. However,
      relationships between CYP2C9 genotype, enzyme activity, metabolism of probe
      substrates, dosage requirements and bleeding complications should be interpreted
      with caution, and further studies are required.

PMID- 11523727
TI  - Population pharmacokinetics of ifosfamide and its dechloroethylated and
      hydroxylated metabolites in children with malignant disease: a sparse sampling
      approach.
AB  - OBJECTIVE: To assess the feasibility of a sparse sampling approach for the
      determination of the population pharmacokinetics of ifosfamide, 2- and 3
      dechloroethyl-ifosfamide and 4-hydroxy-ifosfamide in children treated with single
      agent ifosfamide against various malignant tumours. DESIGN: Pharmacokinetic
      assessment followed by model fitting. PATIENTS: The analysis included 32 patients
      aged between 1 and 18 years receiving a total of 45 courses of ifosfamide 1.2, 2
      or 3 g/m2 in 1 or 3 hours on 1, 2 or 3 days. METHODS: A total of 133 blood
      samples (median of 3 per patient) were collected. Plasma concentrations of
      ifosfamide and its dechloroethylated metabolites were determined by gas
      chromatography. Plasma concentrations of 4-hydroxy-ifosfamide were measured by
      high-performance liquid chromatography. The models were fitted to the data using
      a nonlinear mixed effects model as implemented in the NONMEM program. A cross
      validation was performed. RESULTS: Population values (mean +/- standard error)
      for the initial clearance and volume of distribution of ifosfamide were estimated
      at 2.36 +/- 0.33 L/h/m2 and 20.6 +/- 1.6 L/m2 with an interindividual variability
      of 43 and 32%, respectively. The enzyme induction constant was estimated at
      0.0493 +/- 0.0104 L/h2/m2. The ratio of the fraction of ifosfamide metabolised to
      each metabolite to the volume of distribution of that metabolite, and the
      elimination rate constant, of 2- and 3-dechloroethyl-ifosfamide and 4-hydroxy
      ifosfamide were 0.0976 +/- 0.0556, 0.0328 +/- 0.0102 and 0.0230 +/- 0.0083 m2/L
      and 3.64 +/- 2.04, 0.445 +/- 0.174 and 7.67 +/- 2.87 h(-1), respectively.
      Interindividual variability of the first parameter was 23, 34 and 53%,
      respectively. Cross-validation indicated no bias and minor imprecision (12.5 +/-
      5.1%) for 4-hydroxy-ifosfamide only. CONCLUSIONS: We have developed and validated
      a model to estimate ifosfamide and metabolite concentrations in a paediatric
      population by using sparse sampling.

PMID- 11523728
TI  - Validity and reliability of triaxial accelerometers for inclinometry in posture
      analysis.
AB  - There is a need for objective and quantitative methods for measuring posture and
      movement, so that, for instance, exposure-response relationships for work-related
      musculoskeletal disorders can be established. Inclinometry data have been
      obtained from triaxial accelerometers based on uniaxial solid-state
      accelerometers used in conjunction with a computer program to perform co-ordinate
      transformations. The transducer can be mounted in an arbitrary orientation on a
      body segment, since if two reference positions are recorded, the co-ordinate
      system of the transducer can be transformed to that of the body segment. The
      angular error of the system is small (1.3 degrees), the reproducibility is high
      (0.2 degrees), and the inherent angular noise is small (0.04 degrees) and
      independent of the orientation of the device. Under quasi-static conditions, the
      angular velocities can be derived from the inclinometry data. The angular and the
      angular-velocity errors can be approximated using the relative deviation of the
      acceleration magnitude from gravitation. For applications involving a high degree
      of movement, the accelerometer data are still valid, although they cannot be
      interpreted as inclination. Used in combination with the computer program, the
      transducer can be used to measure posture and movement under static and quasi
      static conditions, which occur in most areas of occupational work. It is shown
      that spherical co-ordinates can be used to present the inclinometry data.

PMID- 11523729
TI  - Development of computer-based environment for simulating the voluntary upper-limb
      movements of persons with disability.
AB  - Upper-limb orthotic systems have been designed for restoring the upper-limb
      functions of individuals with disabilities resulting from spinal cord injury
      (SCI), stroke and muscular dystrophy. These systems employ either functional
      electrical stimulation or external power. It is proposed that, instead of time
      consuming and complicated monitoring using sensors and motion analysis, a
      software simulator with both angular displacement and acceleration parameters can
      facilitate the design of a control strategy for an orthosis. Reaching movements
      of three cervical SCI subjects are used to verify the simulator. A motion
      analysis system is used to measure the range of motion and joint angles during
      hand reaching. Results indicate that quaternion and spline curve techniques are
      suitable for interpolation of the hand reaching movements. The information needed
      for good simulation only compress the shoulder and elbow joint angles in a few
      key postures. Stimulated acceleration signals on the upper-arm segment have a
      high correlation coefficient (> 0.9) and a small root mean squared error (< 0.11
      g) with a real bi-axial accelerometer.

PMID- 11523730
TI  - Measurements of steady turbulent flow through a rigid simulated collapsed tube.
AB  - Axial and transverse components of liquid velocity are measured by laser Doppler
      anemometer in a perspex tube that has been deformed at one point to resemble the
      shape of the throat of a partially collapsed flexible tube, conveying fluid while
      being compressed externally. The Reynolds number is 5900. The flow down-stream of
      the throat consists of two side-jets with reverse flow extending all across the
      cross-section between them. The jets spread out around the central retrograde
      flow zone, initially forming crescents of high-speed forward flow and then, at
      three diameters downstream, an almost complete annulus of forward flow around a
      central zone of lower-speed but now forward flow. Comparison is made between the
      features of this turbulent flow and those of a previously investigated laminar
      flow through the same geometry. In both, retrograde flow ceases between two and
      three diameters downstream of the centre of the throat. However, the laminar flow
      is annular at three diameters downstream, whereas here the jets remain
      influential at that station. The maximum normalised turbulence intensity exceeds
      1.35.

PMID- 11523731
TI  - Estimation and significance testing of cross-correlation between cerebral blood
      flow velocity and background electro-encephalograph activity in signals with
      missing samples.
AB  - Cross-correlation between cerebral blood flow (CBF) and background EEG activity
      can indicate the integrity of CBF control under changing metabolic demand. The
      difficulty of obtaining long, continuous recordings of good quality for both EEG
      and CBF signals in a clinical setting is overcome, in the present work, by an
      algorithm that allows the cross-correlation function (CCF) to be estimated when
      the signals are interrupted by segments of missing data. Methods are also
      presented to test the statistical significance of the CCF obtained in this way
      and to estimate the power of this test, both based on Monte Carlo simulations.
      The techniques are applied to the time-series given by the mean CBF velocity
      (recorded by transcranial Doppler) and the mean power of the EEG signal, obtained
      in 1 s intervals from nine sleeping neonates. The peak of the CCF is found to be
      low (< or = 0.35), but reached statistical significance (p < 0.05) in five of the
      nine subjects. The CCF further indicates a delay of 4-6s between changes in EEG
      and CBF velocity. The proposed signal-analysis methods prove effective and
      convenient and can be of wide use in dealing with the common problem of missing
      samples in biological signals.

PMID- 11523732
TI  - Detection of alpha electro-encephalogram onset following eye closure using four
      location-based techniques.
AB  - Detection of alpha activity in the electro-encephalogram (EEG) has been used
      extensively in neurophysiological studies. Previously applied alpha
      parameterisation techniques, which utilise the amplitude information from a pair
      of differential electrodes, are often susceptible to interference from artifact
      signals. This is an issue if the purpose of detecting the change in alpha wave
      synchronisation is the basis of an environmental control system (ECS). An
      alternative approach to alpha activity detection is proposed that utilises the
      information from an array of electrodes on the scalp to estimate the apparent
      location of alpha activity in the brain. Four methods are described that
      successfully detect the onset of alpha EEG increase following eye closure by
      monitoring the apparent location of alpha activity in the head. The methods use
      Bartlett beamforming, a four-sphere anatomical head model, the MUSIC algorithm
      and a new 'power vector' technique. Of the methods described, the power vector
      technique is found to be the most successful. The power vector technique detects
      the alpha increase associated with eye closure in times that are, on average, 33%
      lower than previously applied alpha detection methods.

PMID- 11523733
TI  - Facilitation of motor evoked potentials in the anterior tibial muscle by
      repetitive subthreshold electrical stimulation.
AB  - Subthreshold electrical stimulation with an intensity less than the threshold for
      evoking M-waves is applied repetitively to the common peroneal nerve via surface
      electrodes. The stimulation intensity is varied by adjusting the pulse width from
      0 to 240 micros, while the pulse interval (40 ms) and current amplitude are kept
      constant. Single magnetic stimuli are applied to the motor cortex using a
      circular coil. Motor evoked potentials are recorded from the anterior tibial
      muscle in six normal subjects for various subthreshold stimulation intensities.
      Signal processing (filtering in the time and frequency domains) removes the
      artifact caused by the subthreshold electrical stimulation from the motor evoked
      potential. Statistically significant motor evoked potential facilitation (p <
      0.05) is observed for pulse widths ranging from 72 to 240 micros in all the
      tested subjects. A pulse width corresponding to 90% of the electrical threshold
      facilitated the motor evoked potential in five of the six subjects.

PMID- 11523734
TI  - Noninvasive characterisation of multiple ventricular events using
      electrocardiographic imaging.
AB  - Distributions of epicardial potentials, calculated from body surface
      electrocardiograms (ECGs), were investigated to determine if they could enable
      detection of multiple sites of ventricular activity. An anatomical model of the
      human ventricular myocardium was used to simulate activation sequences initiated
      at nine different ventricular pairs of sites. From these sequences, body surface
      ECGs were simulated at 352 sites on the torso surface and then used to
      reconstruct epicardial potentials at 202 sites. The criterion for detection of
      dual ventricular events was the presence of two distinct primary potential minima
      in the reconstructed epicardial potentials. The shortest distance between the two
      events in the right ventricle that resulted in the reconstruction of epicardial
      potential patterns, featuring two minima, was 27 mm; the distance between the two
      events in the left ventricle was 23 mm. When Gaussian white noise in the
      simulated body surface potentials was increased from 3 microV to 15 microV and 50
      microV, dual events became more difficult to distinguish. Findings indicate that
      calculated epicardial potentials provide useful visual information about the
      presence of multiple ventricular events that is not apparent in features of body
      surface ECGs, and could be particularly helpful in optimising mapping procedures
      during difficult or unsuccessful radiofrequency ablations of accessory pathways.

PMID- 11523735
TI  - Effect of fibre rotation on the initiation of re-entry in cardiac tissue.
AB  - Transmural rotation of cardiac fibres can have a big influence on the initiation
      of re-entry in the heart. However, owing to computational demands, this has not
      been fully explored in a three-dimensional model of cardiac tissue that has a
      microscopic description of membrane currents, such as the Luo-Rudy model. Using a
      previously described model that is computationally fast, re-entry in three
      dimensional blocks of cardiac tissue is induced by a cross-shock protocol, and
      the activity is examined. In the study, the effect of the transmural fibre
      rotation is ascertained by examining differences between a tissue block with no
      rotation and ones with 1, 2 and 3 degrees of rotation per fibre layer. The
      direction of the re-entry is significant in establishing whether or not re-entry
      can be induced, with clockwise re-entry being easier to initiate. Owing to the
      rotating anisotropy that results in preferential propagation along the fibre
      axis, the timing of the second stimulus in the cross-shock protocol has to be
      changed for different rates of fibre rotation. The fibre rotation either
      increases or decreases the window of opportunity for re-entry, depending on
      whether the activation front is perpendicular or parallel to the fibre direction.
      By varying the transmural extent of the S2, it is found that a deeper stimulus
      has to be applied to the blocks with fibre rotation to create re-entry.
      Increasing the transmural resistance also tends to reduce the extent of the S2
      required to induce re-entry. Results suggest that increasing fibre rotation
      reduces the susceptibility of the tissue to re-entry, but that more complex
      spatiotemporal patterns are possible, e.g. stable figure-of-eight re-entries and
      transient rotors. Three mechanisms of re-entry annihilation are identified: front
      catchup, filling of the excitable gap and core wander.

PMID- 11523737
TI  - Application of empirical mode decomposition to heart rate variability analysis.
AB  - The analysis of heart rate variability, involving changes in the autonomic
      modulation conditions, demands specific capabilities not provided by either
      parametric or non-parametric spectral estimation methods. Moreover, these methods
      produce time-averaged power estimates over the entire length of the record.
      Recently, empirical mode decomposition and the associated Hilbert spectra have
      been proposed for non-linear and non-stationary time series. The application of
      these techniques to real and simulated short-term heart rate variability data
      under stationary and non-stationary conditions is presented. The results
      demonstrate the ability of empirical mode decomposition to isolate the two main
      components of one chirp series and three signals simulated by the integral pulse
      frequency modulation model, and consistently to isolate at least four main
      components localised in the autonomic bands of 14 real signals under controlled
      breathing manoeuvres. In addition, within the short time-frequency range that is
      recognised for heart rate variability phenomena, the Hilbert amplitude component
      ratio and the instantaneous frequency representation are assessed for their
      suitability and accuracy in time-tracking changes in amplitude and frequency in
      the presence of non-stationary and non-linear conditions. The frequency tracking
      error is found to be less than 0.22% for two simulated signals and one chirp
      series.

PMID- 11523736
TI  - Estimation of frequency shift in cardiovascular variability signals.
AB  - Spectral analysis of heart rate (HR) and blood pressure (BP) oscillations has
      traditionally concentrated on spectral power, although a shift in spectral
      frequency characterises the variability better than power in some cases.
      Experimental data were obtained from 14 healthy males in control and
      pharmacological blockade conditions. When parasympathetic control was reduced, LF
      oscillations of HR and BP tend to shift towards lower frequencies. Three
      parameters were compared to estimate the spectral shift within the low frequency
      (LF, 0.04-0.15 Hz) band in HR and BP variability: mean (fmean), median (fmed),
      and central frequency (fc). Parameter variance (pSTD) and sensitivity to noise
      were also estimated using realistic HR, systolic BP (SBP) and diastolic BP (DBP)
      data. fmean showed the lowest parameter variance both for an autoregressive (AR)
      method (SBP pSTD 3.1 vs 4.8 vs 4.7 mHz for fmean, fmed and fc, respectively;
      p<0.001) and an FFT method (SBP pSTD 4.7 vs 7.7 mHz for fmean and fmed,
      respectively; p<0.001). Furthermore, fmean was least sensitive to noise. fc
      showed the poorest performance being especially sensitive to noise. To analyse
      the spectral shift, fmean is preferred, since it performs better than fc, which
      has been used in most previous studies. To quantify the frequency of oscillations
      in cardiovascular signals, the mean frequency is recommended, with analyses
      across different spectral bands.

PMID- 11523738
TI  - Computer simulation of the baroregulation in response to moderate dynamic
      exercise.
AB  - A baroregulation model, based on a previous pulsatile non-linear multielement
      cardiovascular model, is extended and used to study short-term regulation
      mechanisms. Using this model, the responses of several cardiovascular variables
      to different exercise levels are simulated and compared with the experimental
      data reported in the literature. The impact of physiological or pathological
      changes on the short-term regulation of arterial pressure under the stimulus of
      moderate dynamic exercise is then studied. The simulation results indicate that
      baroreflex feedback plays a critical role in the short-term regulation of
      arterial pressure. When the baroreflex gain decreases to one-third of the normal
      value, the response of the mean arterial pressure to moderate dynamic exercise
      and post-exercise recovery time increases by factors of 1.7 and 2.3,
      respectively. Clinical data from 36 subjects (two groups: normal and
      hypertensive) are collected to validate the model. Computer simulations for the
      hypertensive group show that the elastic modulus of the arterial vessel wall is
      increased by 1.5 times, and peripheral resistance is increased by 1.3 times the
      normal value, and the baroreflex gain decreases from 0.55 (for the normal group)
      to 0.40. The simulation results for normal and hypertensive groups agree well
      with the clinical data.

PMID- 11523739
TI  - Numerical simulations of unsteady flows in a stenosed coronary bypass graft.
AB  - Using the finite element method, physiological blood flows through a three
      dimensional model of a coronary graft are numerically analysed. The model
      includes a stenosis shape in the host artery upstream from the anastomosis.
      Recirculating areas, secondary flows, wall shear stress (WSS) and spatial wall
      shear stress gradients (WSSGs) are studied for different flow repartitions and at
      different times in the cycle. The temporal and spatial evolutions of the
      recirculating areas downstream from the stenosis, their interactions with the
      flow issued from the graft and their associated WSSs highlight that the presence
      of the stenosis in the recipient artery is essential for prediction of the
      evolution of a grafting at the beginning of its implantation. The areas
      downstream from the stenosis expansion, non-existent for a host artery without
      stenosis, are submitted to low and oscillating WSS between -0.5 and 0 Nm(-2). The
      stagnation point on the recipient artery floor is subjected to high positive and
      negative WSSGnd values, and its location is dependent on the residual flow
      through the stenosis.

PMID- 11523740
TI  - Myo-electric signals to augment speech recognition.
AB  - It is proposed that myo-electric signals can be used to augment conventional
      speech-recognition systems to improve their performance under acoustically noisy
      conditions (e.g. in an aircraft cockpit). A preliminary study is performed to
      ascertain the presence of speech information within myo-electric signals from
      facial muscles. Five surface myo-electric signals are recorded during speech,
      using Ag-AgCl button electrodes embedded in a pilot oxygen mask. An acoustic
      channel is also recorded to enable segmentation of the recorded myo-electric
      signal. These segments are processed off-line, using a wavelet transform feature
      set, and classified with linear discriminant analysis. Two experiments are
      performed, using a ten-word vocabulary consisting of the numbers 'zero' to
      'nine'. Five subjects are tested in the first experiment, where the vocabulary is
      not randomised. Subjects repeat each word continuously for 1 min; classification
      errors range from 0.0% to 6.1%. Two of the subjects perform the second
      experiment, saying words from the vocabulary randomly; classification errors are
      2.7% and 10.4%. The results demonstrate that there is excellent potential for
      using surface myo-electric signals to enhance the performance of a conventional
      speech-recognition system.

PMID- 11523742
TI  - Critical micelle concentrations of allelopathic substances produced by
      Nannochloris oculata which affect a red tide organism, Gymnodinium breve.
AB  - Laboratory cultures of the green algae Nannochloris oculata and Nannochloris
      eucaryotum are known to cause lysis of Gymnodinium breve, which is Florida's red
      tide organism. Two cytolytic agents were previously identified as methyl
      palmitate and methyl stearate. In this study, the critical micelle concentrations
      of these substances were determined by ultraviolet light and turbidimetric
      methods to be 3.5 +/- 0.3 ppm (methyl stearate) and 4.3 +/- 0.6 (methyl
      palmitate). There were no significant differences in results obtained using the
      two methods.

PMID- 11523741
TI  - Nuclear liver glycoproteins at different stages of chicken embryo development.
AB  - In order to examine whether the patterns of nuclear and chromatin glycoproteins
      change during development the glycoproteins of foetal and adult chicken liver
      were investigated. Nuclear and chromatin proteins from both sources were
      separated by SDS-PAGE, transferred onto Immobilon-P transfer membrane or
      nitrocellulose and tested for concanavalin A (Con A), Galanthus nivalis
      agglutinin (GNA) and Aleuria aurantia agglutinin (AAA) binding. Results revealed
      a similarity in the profiles of nuclear and chromatin glycoproteins recognized by
      Con A from 14-, 16-, 18-day foetal and adult chicken liver. Generally GNA and AAA
      reacted more weakly with glycoproteins from foetal liver compared with the same
      glycoproteins from adult liver.

PMID- 11523743
TI  - Translocation of unstable heterochromatin as the mechanism of sister chromatid
      exchange formation: a proposed hypothesis.
AB  - The phenomenon of sister chromatid exchange has remained an enigma in that the
      actual mechanism for its formation has never been elucidated. It has long been
      suspected that the process involves some form of breakage and rejoining of DNA,
      but that hypothesis has never been proved. Recent work in this laboratory using
      cells from a premature aging disorder (Werner's syndrome) has promulgated the
      hypothesis that heterochromatin may not be an integral structure of chromosomes,
      but rather serves as a surface feature or covering. Furthermore, heterochromatin
      in Werner's syndrome chromosomes was found to be unstable and easily sloughed-off
      the chromosome surface. In this investigation evidence is presented which shows
      that incorporation of bromodeoxyuridine into DNA causes instability in the
      purported heterochromatin covering, resulting in translocation of segments of
      heterochromatin from the unifilarly-substituted chromatid to the bifilarly
      substituted sister chromatid. Such translocation may represent the long-elusive
      mechanism of sister chromatid exchange formation.

PMID- 11523744
TI  - Growth retardation and osteomalacia as a result of ifosfamide nephrotoxicity in a
      3-year-old boy whose genotype reveals the genes encoding glutathione S
      transferases GSTM1 and GSTT1.
AB  - A case of a child with growth retardation and prolonged osteomalacia, as a result
      of chronic renal tubulopathy, following successful therapy for a sacral-coccygeal
      germinal tumour, is described. The male patient was enrolled into the research
      programme for the evaluation of the association between deletion of the genes
      encoding a number of classes of glutathione S-transferases (GST) and adverse
      reactions to alkylating agents. His genotype revealed the genes encoding
      glutathione transferase classes GSTM1 and GSTT1, but these enzymes did not
      provide adequate protection for the tubular cells, from the toxic effects of
      ifosfamide metabolites. Intense chemotherapy resulted in an increased risk of
      chronic side effects. Further studies are necessary for increased understanding
      of the inter-individual variability in the extent and nature of ifosfamide
      nephrotoxicity.

PMID- 11523745
TI  - Steroid hormones regulate programmed cell death: a review.
AB  - Programmed cell death (PCD) is a physiologically active process which is
      essential for the proper functioning of any living tissue. The steroid hormones
      modulate the programme in the immunological and reproductive organs and tissues,
      such as the thymus gland, circulating thymocytes, uterus, vagina, testis, ovary
      and prostrate gland. The influence of steroid hormones on cell death is tissue
      specific; the same hormone can inhibit PCD in one tissue, and may promote PCD in
      another tissue. The roles of apoptosis and terminal differentiation have been
      examined, and the regulation of PCD by steroid hormones, assessed.

PMID- 11523746
TI  - Equivalence of the mediation, confounding and suppression effect.
AB  - This paper describes the statistical similarities among mediation, confounding,
      and suppression. Each is quantified by measuring the change in the relationship
      between an independent and a dependent variable after adding a third variable to
      the analysis. Mediation and confounding are identical statistically and can be
      distinguished only on conceptual grounds. Methods to determine the confidence
      intervals for confounding and suppression effects are proposed based on methods
      developed for mediated effects. Although the statistical estimation of effects
      and standard errors is the same, there are important conceptual differences among
      the three types of effects.

PMID- 11523747
TI  - Modeling prevention program effects on growth in substance use: analysis of five
      years of data from the Adolescent Alcohol Prevention Trial.
AB  - The efficacy of prevention programs is typically determined through analysis of
      covariance. To date, a growth curve modeling approach is not used extensively in
      program evaluation. However, for longitudinal data there are several advantages
      to using this approach as compared to methods comparing means at two time points
      in a piecemeal fashion. In this study, latent growth curve models were used to
      evaluate the effect of a program on the average level of drug use, rate of change
      (growth) of drug use, and acceleration or deceleration in the rate of change of
      drug use. The study relied on data from the Adolescent Alcohol Prevention Trial,
      a randomized longitudinal drug use prevention program. The program consists of
      drug use information, resistance skills training, and normative education
      components. Data regarding cigarette and alcohol use were collected over a 5-year
      period, grade 7 to grade 11. Students receiving the normative education program
      had significantly lower average levels of reported cigarette and alcohol use,
      lower rates of growth for reported cigarette and alcohol use, and less
      deceleration of reported levels of cigarette and alcohol use as compared with the
      control group. Growth curve analysis is a powerful and effective tool with which
      to model change and program efficacy.

PMID- 11523748
TI  - Ethnic and gender differences in psychosocial risk, protection, and adolescent
      alcohol use.
AB  - Theoretical models suggest that many diverse psychosocial factors contribute to
      the etiology of substance use among youth. It has been suggested that substance
      use is a function of the total number of etiologic factors, rather than a
      specific type or set of factors. This study examined whether cumulative
      psychosocial risk and protection measured in the 7th grade predicted alcohol use
      in the 9th grade across ethnically diverse samples of adolescents. Participants
      consisted of black (n = 775) and Hispanic (n = 467) inner-city youth and white
      suburban youth (n = 708). Prevalence rates for alcohol use and risk/protection
      varied more widely based on ethnic group compared to gender. Black youth reported
      the fewest risk factors and lowest levels of alcohol use, white youth reported
      the most risk factors and highest levels of alcohol use, and Hispanic youth
      reported the fewest protective factors and intermediate levels of alcohol use.
      Despite these differences, structural equation modeling indicated that a latent
      factor consisting of cumulative risk, protection, and their interaction
      significantly predicted later alcohol use for the combined sample as well as for
      each ethnic/ gender subgroup. However, the proportion of variance explained in
      alcohol use varied across subgroups, and moderator analyses indicated that
      protection significantly buffered the effects of risk differentially across
      subgroups. The strongest protective effects were observed among black inner-city
      youth. Findings suggest that prevention approaches should focus on enhancing
      protection in addition to reducing risk, particularly among youth with lower
      levels of psychosocial protection.

PMID- 11523749
TI  - Modeling factors influencing enrollment in family-focused preventive intervention
      research.
AB  - The reported study tests an extension of a previously supported model of family
      context and health belief predictors of parental inclination to enroll in
      preventive interventions. The extended model addresses limitations in the prior
      investigation; it examines the role of intervention-related beliefs and
      inclinations on actual enrollment in a skills training intervention research
      project. Model testing was conducted with a sample of 635 parents of 6th graders
      who completed a prospective participation factor survey and were recruited for an
      intervention research project 6 months later. The model fit was strong and all
      but one of the primary hypothesized effects were supported. Notably, both stated
      inclination to enroll in an intervention and in the research project had
      significant positive effects on actual project enrollment occurring 6 months
      later. Perceived intervention benefits and barriers had significant effects on
      both types of stated inclination to enroll. Examination of modification indices
      for the model suggested an additional path linking educational attainment with
      actual enrollment.

PMID- 11523750
TI  - Influence of a family-directed program on adolescent cigarette and alcohol
      cessation.
AB  - Programs to reduce adolescent cigarette or alcohol use by users in general
      populations have only recently been evaluated. Moreover, in spite of the
      substantial influence families have on their children, few family-directed
      programs designed to reduce the prevalence of adolescent smoking and drinking
      have been rigorously evaluated. This paper reports the findings of research
      designed to determine whether a family program reduced use of cigarettes or
      alcohol by users. The program consisted of a series of booklets mailed to
      families and follow-up telephone calls by health educators. A randomized
      experimental design involved families with children ages 12-14 throughout the
      United States. Data were collected by telephone at baseline and 3 and 12 months
      after the program was completed. No statistically significant program effects
      were observed for cessation or decrease in smoking and drinking by users.

PMID- 11523751
TI  - Do parent-imposed delayed licensure and restricted driving reduce risky driving
      behaviors among newly licensed teens?
AB  - Motor vehicle crashes are the leading cause of death and injury to teenagers.
      Crash risks result from their age, inexperience, and risky driving. The purpose
      of this study was to determine whether parent-imposed delayed licensure and
      restricted driving are related to fewer teenage risky driving behaviors. At
      baseline, 275 teenagers with a learner's permit and one of their parents were
      interviewed about driving attitudes and teenage behaviors. One year later, 161 of
      the teenagers had since obtained a provisional license and were reinterviewed
      about time of licensure, parental restrictions on driving, and driving attitudes
      and behaviors. The results indicated that parents delayed licensure until teens
      were "ready," and limited their driving in terms of trip and risk conditions.
      Higher levels of risky driving behaviors were predicted by younger ages at
      licensure and fewer limits on driving in the first month, in addition to male
      gender, higher conflict over driving, lower perceptions of dangers related to
      driving, more problem behaviors at baseline, and more high-risk driving (e.g., at
      night, teenage passengers). Overall, the results indicate that a combination of
      being older at licensure and restricting driving under high-risk conditions at
      licensure may be an effective way to curb teens' risky driving behaviors.

PMID- 11523752
TI  - Neighborhood characteristics of alcohol-related pedestrian injury collisions: a
      geostatistical analysis.
AB  - This study conducted a geostatistical analysis of ecological data to examine the
      relationships of neighborhood characteristics, including alcohol availability and
      alcohol consumption patterns to pedestrian injury collisions. The central
      research question asked whether it was possible to identify unique neighborhood
      characteristics related to alcohol- and non-alcohol-involved pedestrian injuries.
      It was hypothesized that greater numbers of alcohol-involved pedestrian injuries
      would be observed in areas with greater concentrations of alcohol outlets, even
      after adjusting for socioeconomic characteristics, environmental factors, and
      drinking patterns of neighborhood residents. It was also hypothesized that
      independent of drinking patterns and alcohol availability, greater numbers of
      pedestrian injuries would be observed in areas with higher unemployment, lesser
      income, greater population, and a predominance of younger or older age
      populations. Archival and individual-level data from a general population
      telephone survey were obtained from four California communities. The survey data
      included sociodemographic and drinking pattern measures. Archival data included
      environmental measures relevant to pedestrian travel and measures of alcohol
      availability. Units of analysis were geographic areas within each community
      defined by the spatial clustering of telephone survey respondents. The results
      showed that alcohol-involved pedestrian collisions occurred more often in areas
      with greater bar densities and greater population, and where the local population
      reported drinking more alcohol per drinking occasion. Pedestrian collisions not
      involving alcohol occurred more often in lower income areas with greater
      population and cross-street densities, and in areas having either younger or
      older age populations. The identification of neighborhood variables associated
      with pedestrian collisions has important implications for policy formation and
      targeted prevention efforts.

PMID- 11523753
TI  - The Hutchinson Smoking Prevention Project: a lesson on inaccurate media coverage
      and the importance of prevention advocacy.

PMID- 11523754
TI  - Effects of the Positive Action program on achievement and discipline: two matched
      control comparisons.
AB  - This paper reports on the effectiveness of an integrated comprehensive school
      model for character development, problem behavior prevention, and academic
      achievement enhancement. The Positive Action program consists of a school
      curriculum, together with schoolwide climate, family, and community components.
      As evaluated here, the yearly K-6 curriculum consists of over 140 fifteen-to
      twenty-minute lessons per year delivered in school classrooms on an almost daily
      basis. The program is based on theories of self-concept, learning, behavior, and
      school ecology. We use a matched control design and school-level achievement and
      disciplinary data to evaluate program effects on student performance and behavior
      in two separate school districts. The program improved achievement by 16% in one
      district and 52% in another, and reduced disciplinary referrals by 78% in one
      district and 85% in the other. We discuss implications of these replicated
      findings for the prevention of substance abuse and violence, the improvement of
      school performance, and the reform of American schools.

PMID- 11523756
TI  - Breastfeeding and HIV transmission.

PMID- 11523755
TI  - Preventive intervention effects on developmental progression in drug use:
      structural equation modeling analyses using longitudinal data.
AB  - This study examined the plausibility of the gateway hypothesis to account for
      drug involvement in a sample of middle school students participating in a drug
      abuse, prevention trial. Analyses focused on a single prevention approach to
      exemplify intervention effects on drug progression. Improvements to social
      competence reduced multiple drug use at 1- and 2-year follow-ups. Specific
      program effects disrupted drug progression by decreasing alcohol and cigarette
      use over 1 year and reducing cigarette use over a 2-year period. Controlling for
      previous drug use, alcohol was integrally involved in the progression to multiple
      drug use. Subgroup analyses based on distinctions of pretest use/nonuse of
      alcohol and cigarettes provided partial support for the gateway hypothesis.
      However, evidence also supported alternate pathways including cigarette use as a
      starting point for later alcohol and multiple drug use. Findings underscore the
      utility of targeting more than one gateway substance to prevent escalation of
      drug involvement and reinforce the importance of social competence enhancement as
      an effective deterrent to early-stage drug use.

PMID- 11523757
TI  - The S549R (T-->G) cystic fibrosis gene mutation.

PMID- 11523758
TI  - Moderate immunization coverage levels in East Delhi: implications for disease
      control programmes and introduction of new vaccines.
AB  - A vaccination coverage survey conducted in East Delhi in September 1999 showed
      that only 58.6 per cent of the children aged 12-23 months had received the full
      course of the vaccines recommended under the national immunization programme.
      Coverage with the third dose of DTP and oral polio vaccines was around 71 per
      cent, and with BCG and measles vaccines was 83 and 59 per cent, respectively.
      Drop-out rates between DTP1 and DTP3 and between DTP1 and measles immunization
      were 13.8 and 28.7 per cent, respectively. Nine per cent of the children had not
      received a single dose of any vaccine. The main reason for failure to immunize
      was lack of information. There was a marginal increase in DTP3 and OPV3
      immunization coverage levels as recorded through a previous survey in 1996, a
      drop in coverage with measles vaccine from 64.3 to 59 per cent, and a significant
      increase in tetanus toxoid immunization coverage of pregnant women from 79.4 to
      93 per cent. The percentage of children who had not received any vaccine declined
      from 13 to 9 per cent in the period between the two surveys. Coverage with
      hepatitis B vaccine at 14 per cent was only marginally higher than the baseline
      rate of 9 per cent before the vaccine was made available, free of cost, through
      government and municipal corporation health facilities.

PMID- 11523759
TI  - Single small enhancing computed tomographic lesion in Indian children--I:
      Evolution of current concepts.
AB  - Single, small (<20 mm) enhancing CT lesions are the commonest cause of focal
      seizures in Indian children and are also frequently reported from other tropical
      countries. They often resolve spontaneously on follow-up and have therefore led
      to controversies regarding their etiology and appropriate management. Initially,
      these lesions were often considered to be tuberculomas. However, as research
      progressed over the last two decades, solitary cysticercus granuloma has been
      found to be the most likely cause for these lesions. In this article we discuss
      the evolution of current etiological concepts regarding single, small enhancing
      CT lesions among Indian children, and an approach towards management.

PMID- 11523760
TI  - Thrombocytopoenia as marker for HIV exposure in the neonate.
AB  - Thrombocytopoenia is a well-described marker of human immunedeficiency virus type
      1 (HIV) infection of children. After documenting thrombocytopoenia in a HIV
      exposed neonate, who was subsequently shown not to be infected, we evaluated
      thrombocytopoenia (platelets < 150 x 10(9)/l) as a marker for HIV exposure in
      newborns. This is, to our knowledge, the first study of thrombocytopoenia in HIV
      exposed neonates. A retrospective hospital-based descriptive study was performed
      over an 18-month period (July 1997-December 1998). Patients were recruited either
      through identification of known HIV-positive mothers or neonates with
      thrombocytopoenia who were then screened for HIV exposure. For eligibility,
      neonates with either HIV antibodies or direct evidence of infection (p24
      antigenaemia or HIV RNA detected by polymerase chain reaction after 1 month of
      age) were included. Thirty-four HIV-exposed (HIV-ELISA positive) neonates were
      identified, of whom 16 (47 per cent) had thrombocytopenia. In 12 (35 per cent),
      no underlying cause other than HIV was identified. Nine thrombocytopoenic babies
      were infected and seven uninfected. Unexplained thrombocytopoenia, while an
      imperfect marker, should alert the physician to the possibility of HIV exposure.
      It does not necessarily imply HIV infection. A prospective study is recommended
      to evaluate further the sensitivity and specificity of this marker.

PMID- 11523761
TI  - Serum C-reactive protein concentrations in Malaysian children with enteric fever.
AB  - To investigate the role of serum C-reactive protein (CRP) in the diagnosis of
      typhoid fever, we studied 227 febrile Malaysian children hospitalized during a 12
      month period. The children were: culture-positive for Salmonella typhi (Group 1;
      n = 108); culture-negative but with typical clinical features of typhoid fever
      (Group 2; n = 60); or had non-typhoidal illness (Group 3; n = 59). Group 1
      children had the highest serum CRP concentrations (geometric mean [SD range]; 43
      [12-150] mg/l vs. 26 [8-85] mg/l in Group 2 and 21 [4-110] mg/l in Group 3; p <
      0.001). In regression analysis, age, patient group and fever duration were
      independently associated with serum CRP (p < 0.05) but gender was not. In Group 1
      patients, there was a significant positive association between serum CRP and
      Widal O and H agglutinin titres. In receiver-operator characteristic (ROC)
      analysis of serum CRP for Groups 1 and 2 combined, compared with Group 3, the
      area under the curve (AUC) was 0.65. These data show that the serum CRP is
      highest in culture-positive children with enteric fever and reflects the immune
      response to the infection in this group. Nevertheless, serum CRP had relatively
      low sensitivity and specificity for confirmed or clinically diagnosed typhoid
      fever (68 and 58 per cent, respectively at 'cut-off' concentration 30.0 mg/l),
      and an AUC value only moderately above that associated with no predictive power
      (0.5). Although of limited use as a primary diagnostic test, a raised serum CRP
      may still have a place as one of a range of features that facilitate assessment
      of a febrile child in a typhoid-endemic area.

PMID- 11523762
TI  - Postnatal zidovudine in prevention of vertical HIV-1 transmission in a service
      setting.
AB  - We sought to determine the efficacy of a 4-6 week course of zidovudine (ZDV) in a
      group of infants exposed to HIV-1. A retrospective chart review was conducted on
      HIV-1-exposed neonates identified from February 1998 to August 1999. These
      infants received ZDV and their mothers were counselled regarding the risks and
      benefits of breastfeeding. After informed consent was obtained, the HIV-1-status
      of the infant was determined by RNA-PCR after 1 month of age. Thirty-three HIV-1
      exposed neonates were identified; seven infants were excluded, five because of
      insufficient data and two because of maternal ZDV administration. In all but
      three, the diagnosis was suspected because of maternal illness, 19 of 26 mothers
      having either stage 3 or 4 disease. The transmission rate was 15.4 per cent (4 of
      26). Errors in ZDV administration were detected in 20 neonates of whom four were
      infected (p = 1; Fischer's exact test). Antenatal diagnosis of HIV-1 status was
      associated with fewer medication errors in HIV-1-exposed neonates (p = 0.017,
      Fisher's exact test). It was concluded that a transmission rate of 15.4 per cent
      in symptomatic mothers suggests efficacy. Under similar circumstances,
      transmission rates varying between 37 and 67 per cent have been reported.
      Antenatal diagnosis is significantly associated with compliance to the regimen.
      Early identification of at-risk neonates and familiarity with the regimen may
      improve the outcome.

PMID- 11523763
TI  - Hepatitis B--a major threat to childhood survivors of leukaemia/lymphoma.
AB  - This prospective descriptive study was undertaken to determine: the proportion of
      paediatric oncology patients with prior exposure to hepatitis B at cancer
      diagnosis; the risk and risk factors for acquisition of hepatitis B infection
      during chemotherapy; and the development of a prevention policy. Sixty African
      children were included in this study. At the time of cancer diagnosis, 67.7 per
      cent had not been exposed to hepatitis B, and none had active infection. After
      follow-up (median of 20 months; range 4-81 months) 23.3 per cent had active
      hepatitis B infection, which was subclinical in the majority of cases. The
      diagnosis of leukaemia/lymphoma posed a major risk factor for the acquisition of
      active hepatitis B infection (chi-square 7.0; p-value = 0.008), probably due to
      intensive chemotherapy regimens and severity of immunosuppression. No association
      with gender, age, place of origin, or number of blood transfusions was found.
      Patients with leukaemia/lymphoma were at an increased risk for horizontal
      transmission of hepatitis B. A policy of active surveillance for infective
      carriers of hepatitis B infection and passive immunization of seronegative
      immunosuppressed patients must be implemented to limit the endemic infection in
      paediatric oncology units.

PMID- 11523764
TI  - Comparison of safety of glucose oral rehydration solution and maize oral
      rehydration therapy for home management of diarrhoea in Kenya.
AB  - Safety margins and variability in the composition of glucose and maize-based oral
      rehydration therapy (ORT) prepared by mothers in a rural district of Western
      Kenya, are reported here. In a 2-year longitudinal field study, packets
      containing glucose ORS and a home solution made with maize and table salts, were
      provided to the mothers of 6180 children in Kakamega District in two separate sub
      locations. Experienced and trained field workers supported by community
      registered nurses provided training for the preparation and use of ORT during
      weekly visits to every household. On four occasions separated by 4-6 months, a 5
      per cent random sampling was done of the home-prepared solutions actually used
      for the treatment of children with diarrhoea. The water used for preparing ORT
      was also sampled. Samples of 174 glucose-based ORT, 148 maize-salt ORT, and 201
      samples of water were analysed. Only 2 per cent of the maize-based ORT were above
      120 meq/1 sodium (i.e., the safe range of sodium concentration) compared to 17.8
      per cent for glucose solutions (p < 0.001). Home water samples contained
      substantial amounts of salt, which could unpredictably affect the final
      composition of the ORT solutions. We conclude that maize-salt ORT had a better
      margin of safety than glucose-based ORS.

PMID- 11523765
TI  - Treatment of childhood fevers and other illnesses in three rural Nigerian
      communities.
AB  - The seeking of healthcare for childhood illnesses was studied in three rural
      Nigerian communities of approximately 10,000 population each. The aim was to
      provide a baseline understanding of illness behaviour on which to build a
      programme for the promotion of prepackaged chloroquine and cotrimoxazole for
      early and appropriate treatment of childhood fevers at the community level. A
      total of 3117 parents of children who had been ill during the 2 weeks prior to
      interview responded to questions about the nature of the illness and the actions
      taken. Local illness terms were elicited, and the most prevalent recent illness
      and the actions taken. Local illness terms were elicited, and the most prevalent
      recent illnesses were 'hot body' (43.9 per cent), malaria, known as iba (17.7 per
      cent), and cough (7.4 per cent). The most common form of first-line treatment was
      drugs from a patent medicine vendor or drug hawker (49.6 per cent). Only 3.6 per
      cent did nothing. Most who sought care (77.5 per cent) were satisfied with their
      first line of action, and did not seek further treatment. The average cost of an
      illness episode was less than US$2.00 with a median of US$1.00. Specifically,
      chloroquine tablets cost an average of US 29 cents per course. Analysis found a
      configuration of signs and symptoms associated with chloroquine use, to include
      perception of the child having malaria, high temperature and loss of appetite.
      The configuration positively associated with antibiotic use consisted of cough
      and difficult breathing. The ability of the child's care-givers, both parental
      and professional, to make these distinctions in medication use will provide the
      foundation for health education in the promotion of appropriate early treatment
      of childhood fevers in the three study sites.

PMID- 11523766
TI  - The prevalence of hepatitis B, hepatitis C and human immune deficiency virus
      markers in multi-transfused patients.
AB  - All patients presenting with hereditary hemolytic anemia, (n = 143) over a period
      of 18 months were enrolled in a study to evaluate the prevalence of hepatitis B,
      hepatitis C and HIV in multi-transfused patients in Jordan, and to identify
      possible related risk factors. All patients were treated in the Thalassemia Unit
      at Princess Rahma Teaching Hospital. Relevant clinical data were collected. Blood
      specimens were taken from these patients and tested for HbsAg, HbsAb, hepatitis
      core IgMAb, hepatitis core IgGAb, HCVAb, and ELISA for HIV. Fifty-eight (40.5 per
      cent) of the specimens were HCVAb positive, while only five (3.5 per cent) of
      them were positive for HBsAg. None of the specimens were positive for HIV. The
      frequency of blood transfusion and the time of diagnosis before or after 1995,
      were investigated as possible risk factors for viral seropositivity. Only the
      time of diagnosis was a statistically significant risk factor for HCVAb
      positivity (OR = 4.49; p = 0.005). In conclusion, hepatitis C acquisition is a
      serious risk for multi-transfused patients in Jordan. Hepatitis B is relatively
      less common. Blood screening initiated after 1995 in Jordan has significantly
      reduced the risk of hepatitis C associated with blood transfusion.

PMID- 11523767
TI  - Long-term neurological outcome of acute encephalitis.
AB  - To understand the viral etiology of acute childhood encephalitis in Elazig,
      Eastern Turkey, 36 children aged between 4 months and 14 years who were treated
      in a regional medical center between January 1995 and June 1999 were studied.
      Viral etiology was identified in 16 of 34 (47.1 per cent) cases and the most
      frequently detected pathogens was mumps (seven cases, 20.6 per cent). No specific
      etiology was found in 18 (52.9 per cent) cases. Among the survivors, mental
      and/or focal neurological deficits persisted in 18 (52.9 per cent). Two children
      died and 32 survived, of whom 16 were left with no neurological sequel, 10 had
      persistent neurological sequel, and eight recovered with some degree of handicap.
      Improvement in the general health and sanitation of the population, and the
      universal use and development of new vaccination will significantly reduce the
      incidence of viral encephalitis.

PMID- 11523768
TI  - Brain abscess following mastitis in a 3-month-old infant.
AB  - Neonatal mastitis is rare and generally carries a good prognosis, once treated
      appropriately, but systemic spread could lead to complications. A case of a 3
      month-old infant is presented who developed a brain abscess associated with
      neonatal mastitis.

PMID- 11523769
TI  - Peripheral gangrene complicating Salmonella typhi septicaemia in a Gambian
      infant.
AB  - A 1-year-old malnourished boy, who presented with Salmonella typhi septicaemia
      with a 4-day history of febrile illness, dehydration and severe anaemia,
      developed bilateral dry gangrene of the hands and feet. Although he improved
      appreciably, he suffered auto-amputation of the distal phalanges of the left foot
      after 3 weeks of illness. A high index of suspicion and prompt treatment is
      highly critical in the treatment of septicaemia in young children.

PMID- 11523770
TI  - Ciprofloxacin susceptible Salmonella typhi with treatment failure.

PMID- 11523771
TI  - The burden of pneumonia among children.

PMID- 11523772
TI  - The inverted repeats of IS1384, a newly described insertion sequence from
      Pseudomonas putida strain H, represent the specific target for integration of
      IS1383.
AB  - Analysis of a region on plasmid pPGH1 from Pseudomonas putida strain H that is
      flanked by two copies of IS1383 has revealed an additional element with the
      typical features of a bacterial insertion sequence. This new IS element,
      designated IS1384, contains a single ORF of 972 bp, and is flanked by 9-bp
      inverted repeats. Based on sequence homology and structural characteristics of
      the putative transposase it encodes, IS1384 belongs to the IS5 subgroup of the
      IS5 family. Two copies of IS1384 are present on plasmid pPGH1, whereas none could
      be detected on the chromosome of P. putida strain H. Sequence analysis revealed
      the presence of two truncated copies of IS1384 on the second plasmid in this
      strain, pPGH2. The inverted repeats of all IS1384 copies (including the truncated
      ones) are interrupted by the integration of an IS1383 element. All integrations
      were found to be site- and orientation-specific. PCR studies and sequence data
      indicate that IS1383 can form a circular intermediate on excision. In the
      circular form, the previously described 13-bp inverted repeats of IS1383 are
      separated by 10 bp that are identical to the 5-bp motif that flanks each side of
      the element when it is integrated in its target. We provide evidence that these
      additional nucleotides, although not of inverted symmetry, represent an essential
      part of the inverted repeats. Furthermore, the data indicate that IS1383
      integrated into the inverted repeats of IS1384 by a site-specific recombination
      rather than a site-specific insertion event.

PMID- 11523773
TI  - Multiple allelism as a control mechanism in metabolic pathways: GBSSI allelic
      composition affects the activity of granule-bound starch synthase I and starch
      composition in potato.
AB  - Multiple allelism in heterozygous autopolyploid species like potato not only
      occurs for genes that affect morphological characteristics but also for genes
      involved in metabolic pathways. Based on a combination of Southern and PCR
      analyses, at least eight alleles encoding granule-bound starch synthase I
      (GBSSI), which is responsible for amylose biosynthesis, have been identified in
      potato. These alleles were grouped into four classes, distinguishable by Southern
      analysis, and subdivided based on PCR. Despite the heterozygous and polyploid
      character of potato it was possible to assign variation in GBSSI activity to the
      allelic composition at the GBSSI loci within a large population of Solanum
      tuberosum cultivars and Solanum breeding lines. Moreover, the availability of an
      amf allele made it possible to reduce heterogeneity and enabled us to demonstrate
      an effect of GBSSI allelic composition on amylose content. The major difference
      between the alleles identified was the absence or presence of a 140-bp fragment
      at a site 0.5 kb upstream of the ATG start codon of the gene for GBSSI. The
      absence of this 140-bp fragment had a major effect on GBSSI activity and amylose
      content, while the presence of small deletions and simple sequence repeats had no
      obvious effect.

PMID- 11523774
TI  - The cell division genes ftsQ and  ftsZ, but not the three downstream open reading
      frames YFIH, ORF5 and ORF6, are essential for growth and viability in
      Brevibacterium lactofermentum ATCC 13869.
AB  - The three ORFs (YFIH, ORF5 and ORF6) located downstream of the cell division
      genes ftsQ and ftsZ in Brevibacterium lactofermentum were disrupted by single
      homologous recombination events between internal fragments of the corresponding
      genes and the chromosomal sequences. The phenotypes of the disrupted mutants were
      similar to that of the wild type, suggesting that these genes are dispensable for
      growth and viability. However, using different plasmid constructs, it was not
      possible to obtain disrupted ftsZ or ftsQ mutants by single crossover events.
      When the ftsZ or ftsQ gene sequence was disrupted in vitro and used to replace
      the homologous chromosomal gene by double recombination, only single
      recombination events took place, and therefore no disruptants were obtained. It
      may be concluded therefore that, as in Escherichia coli, the cell division genes
      ftsQ and ftsZ are indispensable for growth and viability of B. lactofermentum.
      Northern hybridisation analyses performed using internal fragments of the genes
      coding for YFIH, ORF5 and ORF6 allowed us to dissect their transcriptional
      organization and to confirm the disruption of these genes.

PMID- 11523775
TI  - Gene insertion and replacement in Schizosaccharomyces pombe mediated by the
      Streptomyces bacteriophage phiC31 site-specific recombination system.
AB  - The site-specific recombination system used by the Streptomyces bacteriophage
      phiC31 was tested in the fission yeast Schizosaccharomyces pombe. A target strain
      with the phage attachment site attP inserted at the leu1 locus was co-transformed
      with one plasmid containing the bacterial attachment site attB linked to a ura4+
      marker, and a second plasmid expressing the phiC31 integrase gene. High
      efficiency transformation to the Ura+ phenotype occurred when the integrase gene
      was expressed. Southern analysis revealed that the attB-ura4+ plasmid integrated
      into the chromosomal attP site. Sequence analysis showed that the attBxattP
      recombination was precise. In another approach, DNA with a ura4+ marker flanked
      by two attB sites in direct orientation was used to transform S. pombe cells
      bearing an attP duplication. The phiC31 integrase catalyzed two reciprocal cross
      overs, resulting in a precise gene replacement. The site-specific insertions are
      stable, as no excision (the reverse reaction) was observed on maintenance of the
      integrase gene in the integrant lines. The irreversibility of the phiC31 site
      specific recombination system sets it apart from other systems currently used in
      eukaryotic cells, which reverse readily. Deployment of the phiC31 recombination
      provides new opportunities for directing transgene and chromosome rearrangements
      in eukaryotic systems.

PMID- 11523776
TI  - Sna41goa1, a novel mutation causing G1/S arrest in fission yeast, is defective in
      a CDC45 homolog and interacts genetically with polalpha.
AB  - Proteins involved in the initiation of DNA replication play critical roles in the
      assembly and loading of replication complexes at replication origins. To gain
      further insight into the regulation of initiation, we screened in fission yeast
      for temperature-sensitive mutants which arrested at the G1/S boundary, and
      isolated nine mutants which arrested with a 1C DNA content at 36 degrees C. By
      linkage analysis, two complementation groups were identified which were not
      allelic to known G1 arrest mutations. One of the mutants isolated, sna41goul,
      arrested with a G1 DNA content and expressed a pleiomorphic phenotype, i.e., a
      mixture of cut and cdc phenotypes, at 36 degrees C. The point of arrest was
      identified as after START but before the hydroxyurea-induced block, by taking
      advantage of the mutant rad26.a14, which has a defect in an early S phase
      specific checkpoint, and by performing reciprocal shift experiments. sna41 goal
      is allelic to sna41+, which is homologous to the CDC45 gene of budding yeast, and
      the mutation lies in a motif that is highly conserved in Cdc45-related proteins.
      The temperature sensitivity of the sna41goal mutant can be suppressed to some
      extent by ts mutations in polalpha. Our genetic results are consistent with a
      model in which Cdc45 plays crucial roles in the assembly of the replication
      apparatus at replication origins.

PMID- 11523777
TI  - Dual control of the nodA operon of Azorhizobium caulinodans ORS571 by a nod box
      and a NifA-sigma54-type promoter.
AB  - Earlier studies have shown that the Azorhizohium caulinodans nodA promoter is
      controlled by a host plant-derived flavonoid signal via the transcription
      activator NodD. Here, we report that the transcription of the nodA operon is also
      under the control of NifA-RpoN. A NifA-sigma54-type promoter, P2nodA, is present
      upstream of the nod-box consensus motif of the nodA gene and directs expression
      of a nodA-uidA reporter gene both in free-living bacteria under nitrogen fixation
      conditions and in bacteroids. Mutation of P2nodA reduced, under certain
      conditions, the efficiency of nodulation and accelerated nodule senescence,
      suggesting that the dual control may help to optimize nodule initiation and
      function in the natural context of the symbiosis.

PMID- 11523778
TI  - Disruption of their palindromic arrangement leads to selective loss of DNA
      methylation in inversely repeated gus transgenes in Arabidopsis.
AB  - The transgene locus KH15, which is highly susceptible to silencing in Arabidopsis
      thaliana, contains two inversely repeated beta-glucuronidase (gus) genes
      separated by a palindromic sequence and has a low GUS activity, was found to be
      heavily methylated in the gus coding sequence and in the center of the inverted
      repeat. The locus KHsb67, which is less prone to silencing, was found to be less
      densely methylated in the non-repetitive region that separates the inversely
      repeated gus genes. After the removal of one of the gus genes by Cre-mediated
      recombination, methylation in both loci decreased or was totally lost. Despite
      the presence of a 732-bp palindromic sequence in the deletion line derived from
      KH15, this sequence was not methylated. Whereas the KH15 locus triggers
      methylation of homologous gus genes when placed in trans to them, the deletion
      derivative did not, suggesting that the capacity for cross-talk was severely
      affected by disruption of the palindromic arrangement. This result suggests that
      the transcribed palindromic sequences are required to maintain the methylation of
      both symmetrically and non-symmetrically arranged cytosines.

PMID- 11523779
TI  - Coordinate positive regulation of genes encoding [NiFe] hydrogenases in
      Methanococcus voltae.
AB  - Two transcription units encoding selenium-free [NiFe] hydrogenases in
      Methanococcus voltae are transcribed only upon selenium deprivation. Their
      products replace or complement selenocysteine-containing isoenzymes. The
      transcription units are linked by a 453-bp intergenic region, and are subject to
      both positive and negative transcriptional regulation. The mechanism of positive
      regulation was studied in detail. Mutations in identical 11-bp putative activator
      recognition sites close to each promoter showed that each site is involved in the
      activation of both promoters. Sequence-specific DNA-affinity chromatography
      yielded a 55-kDa protein which specifically recognized the 11-bp sequence. We
      consider this protein to be a transcriptional activator for both transcription
      units.

PMID- 11523780
TI  - Proteins that genetically interact with the Saccharomyces cerevisiae
      transcription factor Gal11p emphasize its role in the initiation-elongation
      transition.
AB  - The GAL11 gene encodes a transcription factor that is a component of the
      SRB/Mediator sub-complex of the RNA polymerase II holoenzyme in the yeast
      Saccharomyces cerevisiae. In agreement with this biochemical characterization,
      Gal11p has been found to be required for optimal production of mRNA from many
      yeast promoters, and recessive mutations in GAL11 have been shown to cause
      pleiotropic defects. Despite this progress, the role of Gal11p in gene regulation
      remains largely unknown. In a multicopy suppressor analysis of a gal11delta
      mutation we have identified genes encoding proteins that are part of, or can
      interact with, the RNA polymerase II transcription complex, as well as factors
      involved in cell cycle regulation. Among the suppressors that are clearly related
      to the transcriptional apparatus, Gal11p genetically interacts with components of
      the SRB/Mediator complex, as well as with factors such as TFIIE and TFIIH that
      are required for promoter clearance and transcription elongation by RNA
      polymerase II. These findings, taken together with published results of
      biochemical and genetic analyses, suggest a role for Galllp at the interface
      between the SRB/Mediator complex and the general transcription factors TFIIE and
      TFIIH, which modulate, via phosphorylation of the CTD, the activity of the RNA
      polymerase II during the transition between initiation and elongation.

PMID- 11523781
TI  - Synergism between base excision repair, mediated by the DNA glycosylases Ntg1 and
      Ntg2, and nucleotide excision repair in the removal of oxidatively damaged DNA
      bases in Saccharomyces cerevisiae.
AB  - In Saccharomyces cerevisiae, inactivation of the two DNA N-glycosylases Ntg1p and
      Ntg2p does not result in a spontaneous mutator phenotype, whereas simultaneous
      inactivation of Ntglp, Ntg2p and Radlp or Rad14p, both of which are involved in
      nucleotide excision repair (NER), does. The triple mutants rad1 ntg1 ntg2 and
      rad14 ntg1 ntg2 show 15- and 22-fold increases, respectively, in spontaneous
      forward mutation to canavanine resistance (CanR) relative to the wild-type strain
      (WT). In contrast, neither of these triple mutants shows an increase in the
      incidence of Lys+ revertants of the lys1-1 ochre allele. Furthermore, the rad1
      ntg1 ntg2 mutant is hypersensitive to the lethal effect of H2O2 relative to WT,
      rad1 and ntg1 ntg2 mutant strains. Moreover, the rad1 ntg1 ntg2 strain is
      hypermutable (CanR and Lys+) upon exposure to H2O2, relative to WT, rad1 and ntg1
      ntg2 strains. Mutagen sensitivity and enhanced mutagenesis in the rad1 ntg1 ntg2
      triple mutant, relative to the other strains tested, were also observed upon
      exposure to oxidizing agents such as tertbutylhydroperoxide and menadione. In
      contrast, the sensitivity of the rad1 ntg1 ntg2 triple mutant to gamma
      irradiation does not differ from that of the WT. However, the triple mutant shows
      an increase in the frequency of Lys+ revertants recovered after gamma
      irradiation. The results reported in this study demonstrate that base excision
      repair (BER) mediated by Ntglp and Ntg2p acts synergistically with NER to repair
      endogenous or induced lethal and mutagenic oxidative DNA damage in yeast. The
      substrate specificity of Ntg1 p and Ntg2p, and the spectrum of lesions induced by
      the DNA-damaging agents used, strongly suggest that oxidized DNA bases,
      presumably oxidized pyrimidines, represent the major targets of this repair
      pathway.

PMID- 11523782
TI  - High mutation rate and mutational bias at (TAA)n microsatellite loci in chickpea
      (Cicer arietinum L.).
AB  - Microsatellites, very short tandemly repeated DNA sequences, are being
      extensively used in evolutionary genetics and molecular breeding of crop plants,
      because of their high degree of allelic variability, which is presumably caused
      by a high rate of mutation that changes microsatellite array length. In humans
      and various animals, mutation rates vary greatly and fall within the range of 10(
      3) to 10(-6). In plants, the mutation rate at microsatellite loci seems to be
      higher than in animals, but no experimental estimates are available yet. Here, we
      report high spontaneous mutation rates (micro) and mutational bias at fifteen
      perfect (TAA)n microsatellite loci in inbred populations of chickpea. We show a
      significantly higher mutation rate, averaged across all loci, in the long-lived
      variety Ghab 2 (mu = 1.0 x 10(-2); detected in 16,050 allele-generations)
      compared to the variety Syrian Local (mu = 3.9 x 10(-3); detected in 15,600
      allele-generations), which has a short life-span, with the majority of mutants
      (96.9%) in both varieties differing by < or = 1 repeat unit. Compared to animals,
      higher mutation rates in chickpea are likely to be due to the presence of long
      (TAA)n microsatellite repeat arrays and the larger number of DNA replications
      that meristematic initials of the plants undergo before reaching the reproductive
      phase. Thus, the long-lived variety undergoes more DNA replications, resulting in
      an accumulation of more mutations than in the variety with the shorter life-span.

PMID- 11523783
TI  - Genome-wide dissection of Fusarium resistance in tomato reveals multiple complex
      loci.
AB  - Resistance to different pathogenic races of Fusarium oxysporum f. sp. lycopersici
      (F. o. lycopersici) was explored at two genomic levels in tomato. Six independent
      Fusarium resistance loci were identified by comparing the responses of a complete
      set of 53 lines carrying different introgressed regions of the Lycopersicon
      pennellii genome in a L. esculentum background. The loci confer varying degrees
      of resistance to different races of the pathogen. Corresponding map positions
      from different tomato species were aligned and in some cases revealed parallel
      resistance to F. o. lycopersici with qualitative changes in race specificities.
      One of the loci identified corresponds to the previously characterized complex
      resistance locus I2, which is involved in resistance to F. o. lycopersici race 2.
      A novel member of this locus, I2C-5, which belongs to the NBS-LRR family of
      resistance genes, was cloned and shown to confer partial resistance in transgenic
      plants. Thus, at a particular complex locus gene members can confer full or
      partial resistance to F. o. lycopersici race 2. The results of our whole-genome
      mapping analysis underline the robust independent origin of resistance to a
      particular disease and demonstrate the conservation of resistance features at
      syntenic loci, together with the rapid diversification of genes for innate
      resistance within loci.

PMID- 11523784
TI  - Identification of genes required for growth under ethanol stress using transposon
      mutagenesis in Saccharomyces cerevisiae.
AB  - The yeast Saccharomyces cerevisiae exhibits high ethanol tolerance compared with
      other microorganisms. The mechanism of ethanol tolerance in yeast is thought to
      be regulated by many genes. To identify some of these genes, we screened for
      ethanol-sensitive S. cerevisiae strains among a collection of mutants obtained
      using transposon mutagenesis. Five ethanol-sensitive (ets) mutants were isolated
      from approximately 7,000 mutants created by transforming yeast cells with a
      transposon (mTn-lacZ/LEU2)-mutagenized genomic library. Although these mutants
      grew normally in a rich medium, they could not grow in the same medium containing
      6% ethanol. Sequence analysis of the ets mutants revealed that the transposon was
      inserted in the coding regions of BEM2, PAT1, ROM2, VPS34 and ADA2. We
      constructed deletion mutants for these genes by a PCR-directed disruption method
      and confirmed that the disruptants, like the ets mutants, were ethanol sensitive.
      Thus, these five genes are indeed required for growth under ethanol stress. These
      mutants were also more sensitive than normal cells to Calcofluor white, a drug
      that affects cell wall architecture, and Zymolyase, a yeast lytic enzyme
      containing mainly beta-1,3- glucanase, indicating that the integrity of the cell
      wall plays an important role in ethanol tolerance in S. cerevisiae.

PMID- 11523785
TI  - Genetic selection in Saccharomyces of mutant mammalian adenylyl cyclases with
      elevated basal activities.
AB  - We show that co-expression of rat Galphas together with type I, II, IV, or VI
      mammalian adenylyl cyclase (AC) can suppress the growth defect of cyr1 strains of
      Saccharomyces cerevisiae, which lack a functional endogenous AC. Complemention of
      cvr1 is not observed in the absence of Galphas, indicating that the mammalian ACs
      retain their normal regulatory behavior in yeast. Selection for Galphas
      independent growth of (cyr1 strains expressing type IV AC yielded several ACIV
      mutants with enhanced basal activity, each of which had a single amino acid
      substitution in the conserved C1a or C2a region of the protein. Expression of two
      of the mutant ACs in HEK293 cells resulted in increased levels of cAMP and
      elevated adenylyl cyclase activity. Further selection for reverting mutations in
      one of these constitutively active AC mutants yielded three independent
      intragenic suppressor mutations. The distribution of the activating and
      suppressor mutations throughout both C1a and C2a is consistent with a model in
      which the enhanced basal activity results from an increase in the affinity
      between C1a and C2a. These results demonstrate the utility of Saccharomyces as a
      tool for the identification of informative mutant forms of mammalian ACs.

PMID- 11523786
TI  - Site-directed mutagenesis and phylogenetic comparisons of the Escherichia coli
      Tus protein: DNA-protein interactions alone can not account for Tus activity.
AB  - The Tus protein of Escherichia coli is capable of arresting DNA replication in an
      orientation-dependent manner when bound to specific sequences in the bacterial
      chromosome called Ter sites. Arrest of DNA replication has been postulated to
      occur either by a barrier mechanism, where Tus acts as a physical block to
      replication fork progression, or through protein-protein interactions between Tus
      and some component of the replication fork. A previous mutational analysis of Tus
      suggested that the amino acids in the L1 loop might play a role in replication
      arrest. Site-directed mutagenesis of amino acids in the L1 loop and other amino
      acid residues on the "non-permissive" face of Tus was performed to identify
      residues that affected Tus function. One mutant, E47Q, gave results that are
      inconsistent with the barrier model, showing a greater affinity for the Ter site
      (with a t 1/2 of 348 min versus 150 min for wild-type Tus) but a reduced ability
      to arrest DNA replication in vivo. In addition to the site-directed mutagenesis
      studies, the tus genes of Salmonella, Klebsiella, and Yersinia were sequenced and
      the proteins expressed in E. coli to assess their ability to arrest DNA
      replication. The results presented here support a role for protein-protein
      interactions in Tus function, and suggest that residues E47 and E49 participate
      in replication fork arrest.

PMID- 11523787
TI  - Ionising radiation induces the expression of PARP-1 and PARP-2 genes in
      Arabidopsis.
AB  - By screening for Arabidopsis genes activated by ionising radiation (IR)-induced
      DNA damage, we have isolated a cDNA hybridising with a 3.2-kb mRNA that
      accumulates rapidly and strongly in irradiated cell suspensions or whole plants.
      The cDNA codes for a 110-kDa protein that is highly homologous to the 116-kDa
      vertebrate poly(ADP-ribose) polymerase (PARP-1). It is recognised by a human anti
      PARP-1 antibody, binds efficiently to DNA strand interruptions in vitro, and
      catalyses DNA damage-dependent (ADP-ribose) polymer synthesis. We have named this
      protein AtPARP-1. We have also extended our observations to the Arabidopsis app
      (AtPARP-2) gene, demonstrating for the first time that IR-induced DNA strand
      interruptions induce rapid and massive accumulation of AtPARP-1 and AtPARP-2
      transcripts, whereas dehydration and cadmium preferentially induce the
      accumulation of AtPARP-2 transcripts. The IR-induced PARP gene expression seen in
      Arabidopsis is in striking contrast to the post-translational activation of the
      PARP-1 protein that is associated with genotoxic stress in animal cells. AtPARP-1
      transcripts accumulate in all plant organs after exposure to ionising radiation,
      but this is followed by an increase in AtPARP-1 protein levels only in tissues
      that contain large amounts of actively dividing cells. This cell-type specific
      accumulation of AtPARP-1 protein in response to DNA damage is compatible with a
      role for the AtPARP-1 protein in the maintenance of DNA integrity during
      replication, similar to the role of "guardian of the genome" attributed to its
      animal counterpart.

PMID- 11523788
TI  - Isolation and characterization of four novel parsley proteins that interact with
      the transcriptional regulators CPRF1 and CPRF2.
AB  - The common plant regulatory factors (CPRFs) from parsley are transcription
      factors with a basic-leucine-zipper motif that bind to cis-regulatory elements
      frequently found in promoters of light-regulated genes. Proposed to function in
      concert with members of other transcription factor families, CPRFs regulate the
      transcriptional activity of many target genes. Here, we report that, in contrast
      to CPRF2, which operates as a transcriptional activator, CPRF1 functions as
      repressor in vivo. Two-hybrid screens using CPRF1 and CPRF2 as "baits" resulted
      in the isolation of four novel parsley proteins which interact with either CPRF1
      or CPRF2 in vivo. Three of these factors represent new parsley bZIP factors,
      designated CPRF5-CPRF7, whereas the fourth, named CPRF1-interacting protein
      (CIP), shows no homology to any other known protein. CPRF5 and CIP specifically
      interact with CPRF1, whilst CPRF6 and CPRF7 exclusively form heterodimers with
      CPRF2. CPRF5, CPRF6 and CPRF7 are transcription factors that exhibit sequence
      specific DNA-binding as well as transactivation abilities, whereas the function
      of CIP remains elusive. The newly isolated CPRFs and CIP are constitutively
      localized in the nucleus in parsley protoplasts. Furthermore, mRNA accumulation
      studies revealed that the expression of these novel bZIP genes and CIP is not
      altered by exposure to light. We discuss the possible roles of the newly
      identified proteins in CPRF1- and CPRF2-dependent target gene expression.

PMID- 11523789
TI  - Characterization and mapping of Rpi1, a late-blight resistance locus from diploid
      (1EBN) Mexican Solanum pinnatisectum.
AB  - Solanum is a diverse genus with over 200 species occupying a range of habitats
      from the Southwestern United States to Central Chile. Germplasm evaluations have
      focused on species that can be crossed with S. tuberosum, while Mexican diploid
      (2n = 2x = 24) Solanum species with an Endosperm Balance Number (EBN) of 1 have
      received less attention because of poor crossability due to their ploidy and EBN.
      Recent changes in Phytophthora infestans populations have increased the need for
      new sources of genetic resistance to this fungus. We have characterized
      resistance to P. infestans in the Mexican 2x(1EBN) species S. pinnatisectum. An
      interspecific hybrid between resistant S. pinnatisectum and susceptible S.
      cardiophyllum plants was backcrossed to S. cardiophyllum to generate a family
      segregating for late-blight resistance. The diploid (1EBN) genetic map generated
      with 99 RFLP markers revealed extensive synteny with previously published potato
      maps. A single dominant late-blight resistance locus (Rpi1) from S. pinnatisectum
      was mapped to chromosome 7, a region previously not associated with late-blight
      resistance. Characterization of the P.infestans isolate used for disease
      evaluations revealed that it possessed the avirulence gene corresponding to the
      R9 resistance locus, indicating that Rpi1 could possibly correspond to R9.

PMID- 11523790
TI  - Molecular cloning and characterization of a gene encoding the 29-kDa proteasome
      subunit from Trypanosoma cruzi.
AB  - Antiserum raised against purified Trypanosoma cruzi proteasomes was used to
      isolate two cDNA clones, tcpr29 and tcpr29B, and the corresponding genomic
      sequence, termed tcpr29A. Both cDNAs and the gene contain a 798-bp ORF, coding
      for a 266-amino acid protein, with a predicted molecular mass of 29 kDa. Sequence
      comparisons show that the protein encoded by tcpr29 belongs to the alpha6
      subfamily of proteasome subunits. Southern analysis indicated that tcpr29 subunit
      is encoded by a single-copy gene which maps to chromosome 20 of the CL Brener
      clone. Allelic variants were found in other T. cruzi isolates, suggesting
      heterozygosity for the gene in some and homozygosity in other strains. A spliced
      leader addition site was identified 123 bp upstream from the start codon,
      generating a stable 1.5-kb transcript. Western analysis revealed that tcpr29A is
      constitutively expressed during the life cycle of the parasite.

PMID- 11523791
TI  - A homologue of the Rad18 postreplication repair gene is required for DNA damage
      responses throughout the fission yeast cell cycle.
AB  - Cells activate DNA repair pathways and cell cycle checkpoints when they suffer
      damage to their genome. They also activate tolerance pathways that facilitate
      survival. In Escherichia coli, a mechanism known as postreplication repair (PRR)
      is used to bypass lesions that would otherwise present a physical block to DNA
      polymerase. PRR has also been proposed to occur in eukaryotic cells, although the
      partitioning of DNA synthesis to a discrete S-phase would suggest that it is only
      operative within a defined period of the cell cycle. Eukaryotic PRR has been most
      extensively studied in the budding yeast Saccharomyces cerevisiae. Two important
      genes for components of this repair pathway are RAD6, which encodes an ubiquitin
      conjugating enzyme, and RAD18, which encodes a RING-finger protein and forms a
      heterodimer with Rad6p. Rad18p can also bind to DNA. We report here the
      identification of the Schizosaccharomyces pombe homologue of RAD18, which we have
      denoted rhp18. rhp18 mutants are hypersensitive to DNA-damaging agents, but show
      this hypersensitivity throughout the cell cycle. rhp18 mutants are characterised
      by a longer than usual DNA damage checkpoint arrest that is required for their
      residual viability following irradiation. Genetic analyses show that rhp18
      controls a unique DNA damage repair/tolerance pathway that extends beyond the
      requirement to tolerate damage during S-phase, suggesting a broader definition of
      the function of this eukaryotic PRR protein.

PMID- 11523792
TI  - Defective plasmid partition in ftsH mutants of Escherichia coli.
AB  - FtsH is an ATP-dependent protease that is essential for cell viability in
      Escherichia coli. The essential function of FtsH is to maintain the proper
      balance of biosynthesis of major membrane components, lipopolysaccharide and
      phospholipids. F plasmid uses a partitioning system and is localized at specific
      cell positions, which may be related to the cell envelope, to ensure accurate
      partitioning. We have examined the effects of ftsH mutations on the maintenance
      of a mini-F plasmid, and have found that temperature-sensitive ftsH mutants are
      defective in mini-F plasmid partition, but not replication, at permissive
      temperature for cell growth. A significant fraction of replicated plasmid
      molecules tend to localize close together on one side of the cell, which may
      result in failure to pass the plasmid to one of the two daughter cells upon cell
      division. By contrast, an ftsH null mutant carrying the suppressor mutation sfhC
      did not affect partitioning of the plasmid. The sfhC mutation also suppressed
      defective maintenance in temperature-sensitive ftsH mutants. Using this new
      phenotype caused by ftsH mutations, we also isolated a new temperature-sensitive
      ftsH mutant. Mutations in ftsH cause an increase in the lipopolysaccharide/
      phospholipid ratio due to stabilization of the lpxC gene product, which is
      involved in lipopolysaccharide synthesis and is a substrate for proteolysis by
      the FtsH protease. It is likely that altered membrane structure affects the
      localization or activity of a putative plasmid partitioning apparatus located at
      positions equivalent to 1/4 and 3/4 of the cell length.

PMID- 11523793
TI  - Enhancers and core promoter elements are essential for the activity of a cryptic
      gene activation sequence from tobacco, tCUP.
AB  - Cryptic gene regulatory elements are sequences that are inactive at their native
      locations in the genome but have the ability to become functional when positioned
      adjacent to genes. We have recently isolated such a cryptic sequence from
      tobacco, tCUP, that can act as a promoter. A 135-bp fragment spanning extending
      from position -197 to -62, relative to the transcription start site, was found to
      promote GUS expression in all of the major organs of transgenic Arabidopsis
      plants. Furthermore, this 135-bp fragment complemented the -46 minimal promoter
      of CaMV 35S and conferred constitutive expression on transgenic Arabidopsis
      plants. An electrophoretic mobility-shift assay showed that nuclear proteins
      prepared from tobacco leaves interact with the 135-bp fragment. tCUP has a core
      promoter that lacks the TATA consensus sequence but addition of a TATA-box
      sequence increased the core promoter activity by three-fold. The sequence
      surrounding the transcription start site of tCUP has sequence similarity with the
      initiator element (Inr), and deletion of this sequence significantly reduced
      promoter activity, suggesting that an essential Inr element may exist in the tCUP
      core promoter. Fusion of the GCC-box enhancer element from pathogenesis-related
      genes to the core promoter elevated tCUP core promoter activity. Our study
      indicates that cryptic promoters are similar in composition and organization to
      promoters associated with expressed genes and that their promoter elements can be
      combined to create composite promoters that are fully functional. This data
      provides direct evidence that the expression pattern of plant genes can be
      influenced by cryptic gene regulatory elements when they are brought into
      juxtaposition with genes through DNA rearrangements.

PMID- 11523794
TI  - Drosophila RNase H1 is essential for development but not for proliferation.
AB  - Ribonucleases H (RNases H) recognize and specifically degrade RNA that is bound
      to complementary DNA and are thought to be involved in DNA replication and
      transcriptional regulation. Though it was previously shown that bacterial RNases
      H participate in DNA synthesis, none of the known mutations in RNase H genes in
      either prokaryotes or lower eukaryotes is lethal. Here, we report the
      characterization of the first loss-of-function mutation in an RNase H1 gene in a
      metazoan organism, Drosophila melanogaster. Genetic studies of this mutant showed
      that this gene is essential for metamorphosis in Drosophila. However, disruption
      of the RNase H1 gene does not affect proliferation, but probably alters the
      regulation of gene expression. The lethal phenotype of this mutant also
      demonstrates that RNase H1 activity in Drosophila cannot be provided by other
      cellular RNase H activities. Analysis of the developmental and spatial expression
      profiles of a reporter gene placed under the control of the RNase H1 promoter
      revealed increased expression in several larval tissues. In salivary glands this
      increase was shown to be inducible by treatment with ecdysone.

PMID- 11523795
TI  - Structure, expression and products of the ribosomal RNA operons of
      Rhodopseudomonas palustris No. 7.
AB  - Rhodopseudomonas palustris strains carry one or two ribosomal rRNA operons, and
      those with duplicated rrn operons grow faster. The two rrn operons in R.
      palustris No. 7 are virtually identical over a 54,70-bp stretch containing the
      genes for 16S rRNA, tRNAile, tRNAala, 23S rRNA and 5S rRNA, as well as the
      intergenic spacers and part of the extragenic spacer. In R. palustris, unlike
      most bacteria with multiple rrn operons, the putative promoter sequences of the
      two operons are highly diverged, suggesting possible functional differentiation.
      By simultaneous primer-extension analysis of both pre-rRNAs, we detected a two
      fold higher level of expression from rrnA under photoautotrophic conditions.
      Alteration of the conditions of growth leads to changes in the relative levels of
      expression of the two operons. Within the 5,470-bp segment, only two sequence
      differences are found between the 23S rRNA genes; one is at the center of the 23S
      rRNA molecule and affects a site of unknown function, and the other is within or
      immediately adjacent to sequences involved in processing of the 5' 23S rRNA IVS.
      In vitro processing of 5' IVS-containing 23S rRNA precursors from each operon
      does not reveal any detectable difference between them. The 5' ends of the mature
      16S, 23S, and 5S rRNAs were determined by primer-extension analysis, and the 3'
      end of 23S rRNA was determined by RNA linker ligation-mediated cDNA cloning. The
      5' and 3' ends of the R. palustris 23S rRNA molecule are extensively processed,
      suggesting that, unlike the situation in the established eubacterial model, these
      ends cannot basepair.

PMID- 11523796
TI  - Intracellular apolipoprotein E affects Amyloid Precursor Protein processing and
      amyloid Abeta production in COS-1 cells.
AB  - The apoE gene has been identified as a major susceptibility locus for late-onset
      Alzheimer's disease (LOAD). The epsilon4 allele greatly reduces age of onset of
      LOAD as compared to the wild-type 3 allele. The molecular mechanism(s) underlying
      the association has not yet been fully elucidated. The apoE protein has been
      shown to physically interact with the Abeta region of the Amyloid Precursor
      Protein (APP), but also with the ectodomain of the APP holoprotein itself. In
      this study we have used apoE fusion proteins containing either the ER retention
      sequence KDEL or trans-Golgi network (TGN) signal sequence in order to define
      potential apoE-mediated alterations in APP protein processing. Co-expression and
      pulse-chase experiments showed that a functional apoE:APP interaction occurs
      intracellularly which directly affects maturation and subsequently the secretion
      kinetics of APP. In addition, an epsilon4 allele-specific induction of Abeta
      production has been demonstrated. apoE3 resulted in increased Abeta production
      only when targeted to the ER, as observed in cells transfected with an apoE3KDEL
      fusion protein as well as following treatment with brefeldin A. The findings
      suggest that in cells that express both apoE and APP, such as astrocytes and
      microglia, a functional apoE:APP interaction may occur which modulates APP
      processing and Abeta production.

PMID- 11523797
TI  - Promoter sequences regulated by the calcineurin-activated transcription factor
      Crz1 in the yeast ENA1 gene.
AB  - In Saccharomyces cerevisiae the transcription of the ENA1 gene is modulated by
      multiple transduction pathways that respond to osmotic, ionic and nutrient
      stresses. We have investigated the molecular mechanisms involved in ENA1
      induction by the calcium-calcineurin-activated transcription factor Crzl/Tcn1. We
      found in the ENA1 promoter a calcium-responsive, Crzl-dependent upstream
      activating region (UASENA1) located between -713 bp and 826 bp relative to the
      translation start. This region contains two separate control elements: the
      upstream element (5'-GAATGGCTG-3') between -813 and -821 binds Crzlp with lower
      affinity and mostly contributes to basal ENA1 expression, whereas the downstream
      element (5'-GGGTGGCTG-3') between 727 and 719 binds Crz1p with higher affinity
      and is a major determinant of the induction response to calcium.

PMID- 11523798
TI  - Genetic variation in parthenogenetic Caucasian rock lizards of the genus Lacerta
      (L. dahli, L. armeniaca, L. unisexualis) analyzed by DNA fingerprinting.
AB  - Multilocus DNA fingerprinting has been used to study the variability of some mini
      and microsatellite sequences in parthenogenetic species of Caucasian rock
      lizards of the genus Lacerta (L. dahli, L. armeniaca and L. unisexualis). We
      demonstrate that these clonally reproducing lizards possess species-specific DNA
      fingerprints with a low degree of intra- and interpopulation variation. Mean
      indices of similarity obtained using M13 DNA, (GACA)4 and (TCC)50 as probes were
      0.962 and 0.966 in L. dahli and L. armeniaca, respectively. The mean index of
      similarity obtained using M 13 and GATA probes in L. unisexualis was estimated to
      be 0.95. However, despite the high degree of band-sharing, variable DNA fragments
      were revealed in all populations with the microsatellite probes. An particularly
      high level of variability was observed for (TCC)n microsatellites in populations
      of L. unisexualis. In fact TCC-derived DNA fingerprints were close to being
      individual-specific, with a mean index of similarity of 0.824. Fingerprint
      analysis of parthenogenetic families of L. armeniaca showed that all maternal
      fragments were inherited together by the progeny, and no differences in
      fingerprint patterns were observed. On the other hand, while identical DNA
      fingerprints were obtained from L. unisexualis families with M13 and (GATA)4
      probes, use of the (TCC)50 probe revealed remarkable intrafamily variation in
      this species. It is assumed that the genetic heterogeneity observed in
      parthenogenetic populations may be explained, at least in part, by the existence
      of genetically unstable microsatellite loci. Our data serve to illustrate
      processes of spontaneous mutagenesis and the initial stages of clonal
      differentiation in natural populations of the lizard species studied.

PMID- 11523799
TI  - Identification of paralogous HERV-K LTRs on human chromosomes 3, 4, 7 and 11 in
      regions containing clusters of olfactory receptor genes.
AB  - A locus harboring a human endogenous retroviral LTR (long terminal repeat) was
      mapped on the short arm of human chromosome 7 (7p22), and its evolutionary
      history was investigated. Sequences of two human genome fragments that were
      homologous to the LTR-flanking sequences were found in human genome databases:
      (1) an LTR-containing DNA fragment from region 3p13 of the human genome, which
      includes clusters of olfactory receptor genes and pseudogenes; and (2) a fragment
      of region 21q22.1 lacking LTR sequences. PCR analysis demonstrated that LTRs with
      highly homologous flanking sequences could be found in the genomes of human,
      chimp, gorilla, and orangutan, but were absent from the genomes of gibbon and New
      World monkeys. A PCR assay with a primer set corresponding to the sequence from
      human Chr 3 allowed us to detect LTR-containing paralogous sequences on human
      chromosomes 3, 4, 7, and 11. The divergence times for the LTR-flanking sequences
      on chromosomes 3 and 7, and the paralogous sequence on chromosome 21, were
      evaluated and used to reconstruct the order of duplication events and retroviral
      insertions. (1) An initial duplication event that occurred 14-17 Mya and before
      LTR insertion - produced two loci, one corresponding to that located on Chr 21,
      while the second was the ancestor of the loci on chromosomes 3 and 7. (2)
      Insertion of the LTR (most probably as a provirus) into this ancestral locus took
      place 13 Mya. (3) Duplication of the LTR-containing ancestral locus occurred 11
      Mya, forming the paralogous modern loci on Chr 3 and 7.

PMID- 11523800
TI  - Transcription of mutS- and mutL-homologous genes during meiosis in Saccharomyces
      cerevisiae and identification of a regulatory cis-element for meiotic induction
      of MSH2.
AB  - We have analysed the levels of mRNA transcripts of the mutS- and mutL-homologous
      genes of the yeast Saccharomyces cerevisiae during the course of meiosis, by
      quantitative RT-PCR. We found that all mutS homologues (MSH1-6) were induced
      during meiosis, whereas no evidence for regulation of the mutL homologues (PMS1,
      MLH1-3) was obtained. Temporal expression patterns indicative of co-regulation
      were observed for the gene pairs MSH4/MSH5 and MSH2/ SPO11. Sequence comparisons
      of the 5' flanking regions revealed similar sequence stretches in the respective
      gene pairs, which may constitute regulatory elements. Similar sequences were also
      found in the 5' flanking regions of the pairs MSH1/MSH3 and MSH1/MSH6. Upstream
      of MSH2 three closely spaced sequences similar to UASH elements were found, which
      - surprisingly are located within the coding region of SPO21. Deletion of these
      elements resulted in loss of meiotic induction of MSH2. Genetic analysis of
      homozygous deletion mutants did not reveal any differences from wild type with
      respect to genetic distance estimates, aberrant segregation, or suppression of
      homoeologus recombination in an interspecies cross with Saccharomyces paradoxus.

PMID- 11523801
TI  - The N-terminal region of Sgs1, which interacts with Top3, is required for
      complementation of MMS sensitivity and suppression of hyper-recombination in sgs1
      disruptants.
AB  - The SGS1 gene of Saccharomyces (cerevisiae is a homologue of the genes affected
      in Bloom's syndrome, Werner's syndrome, and Rothmund-Thomson's syndrome.
      Disruption of the SGS1 gene is associated with high sensitivity to methyl
      methanesulfonate (MMS) and hydroxyurea (HU), and with hyper-recombination
      phenotypes, including interchromosomal recombination between heteroalleles. SGS1
      encodes a protein which has a helicase domain similar to that of Escherichia coli
      RecQ. A comparison of amino acid sequences among helicases of the RecQ family
      reveals that Sgs1,WRN, and BLM share a conserved region adjacent to the C
      terminal part of the helicase domain (C-terminal conserved region). In addition,
      Sgs1 contains two highly charged acidic regions in its N-terminal region and the
      HRDC (helicase and RNaseD C-terminal) domain at its C-terminal end. These regions
      were also found in BLM and WRN, and in Rqh1 from Schizosaccharomyces pombe. In
      this study, we demonstrate that the C-terminal conserved region, as well as the
      helicase motifs, of Sgs1 are essential for complementation of MMS sensitivity and
      suppression of hyper-recombination in sgs1 mutants. In contrast, the highly
      charged acidic regions, the HRDC domain, and the C-terminal 252 amino acids were
      dispensable for the complementation of these phenotypes. Surprisingly, the N
      terminal 45 amino acids of Sgs1 were absolutely required for the suppression of
      the above phenotypes. Introduction of missense mutations into the region encoding
      amino acids 4-13 abolished the ability of Sgsl to complement MMS sensitivity and
      suppress hyper-recombination in sgs1 mutants, and also prevented its interaction
      with Top3, indicating that interaction with Top3 via the N-terminal region of
      Sgs1 is involved in the complementation of MMS sensitivity and the suppression of
      hyper-recombination.

PMID- 11523802
TI  - Functional analysis of the yeast Ran exchange factor Prp20p: in vivo evidence for
      the RanGTP gradient model.
AB  - Numerous cellular processes rely on the movement of macromolecules into and out
      of the nucleus. The primary regulator of this movement is the small GTPase Ran.
      Like other small GTPases, the nucleotide-bound state of Ran is regulated by
      effectors that enhance the rate of nucleotide exchange or hydrolysis. Current
      models for vectorial nuclear transport suggest that it is the strict
      compartmentalization of these Ran effector molecules that generates a gradient of
      RanGTP between the nucleus and the cytoplasm to impart directionality to the
      transport process. Here we investigate the mechanism by which the Ran exchange
      factor is targeted to the nucleus, and test the impact of disrupting this nuclear
      compartmentalization on nucleocytoplasmic transport in vivo. Our results indicate
      that in Saccharomycces cerevisiae the nucleotide exchange factor Prp20p can be
      targeted to the nucleus via a classical nuclear localization sequence. This
      transport mechanism is dependent both on Ran and the receptor that recognizes the
      nuclear localization sequence, importin alpha. Mutations in the evolutionarily
      conserved nuclear localization sequence only partially inhibit nuclear import of
      Prp20p, suggesting the existence of a secondary mechanism for this critical
      nuclear targeting. In an in vivo test of the RanGTP gradient model, we
      demonstrate that overexpression of a functional cytoplasmic exchange factor
      inhibits cell growth and blocks both protein import and RNA export in wild-type
      cells that contain the endogenous nuclear Prp20 protein. Taken together, our
      results provide in vivo evidence for the idea that the compartmentalization of
      the exchange factor serves as a mechanism for establishing directional nuclear
      transport.

PMID- 11523803
TI  - The origin and maintenance of the small repeat in the bean mitochondrial genome.
AB  - The genesis of small repeats involved in infrequent recombinations in plant
      mitochondrial genomes remains unclear. We propose that at least some of the small
      repeats are generated in a similar way to the large, highly recombinogenic, plant
      mitochondrial repeats. A 314-bp sequence was detected as a small, rarely
      recombining mitochondrial repeat in the genus Phaseolus. Two of the
      recombinational forms were predominant, while two others were found in
      substoichiometric amounts in the species P. vulgaris, P. polyanthus and P.
      coccineus. However, the pairs of predominant and substoichiometric forms were
      distinct in each genome, indicating that a mechanism other than recombination is
      responsible for their maintenance in high or low copy number. In P. lunatus,
      which is phylogenetically quite remote from the other species examined, only one
      form of the 314-bp repeat was predominant, while the other forms were present in
      substoichiometric amounts. In this genome, we also identified sequences
      containing the terminal 11 or 7 bp of the 314-bp repeat. These configurations
      could serve as intermediates during generation of the repeat. We presume that two
      site-specific recombinations between the intermediates and the predominant form
      found in P. lunatus resulted in creation of the two new forms of the repeat. The
      fourth form of the repeat appeared after a further recombination that occurred at
      the substoichiometric level. The nature of this recombination, whether site
      specific or homologous, is discussed. Beyond the evident similarities between the
      model presented in this work and the three-recombination models previously
      proposed to explain the formation of large, frequently recombining repeats, we
      did not detect any specific deletion associated with generation of the repeat.

PMID- 11523804
TI  - Metal transporters that contribute copper to metallochaperones in Saccharomyces
      cerevisiae.
AB  - Copper metallochaperones represent a new family of soluble, low-molecular-weight
      proteins that function to deliver copper to specific sites within a cell. How the
      metallochaperones acquire their copper, however, is not known. In this study, we
      have conducted a survey of known metal ion transporters in bakers' yeast,
      Saccharomyces cerevisiae, to identify those that contribute copper to pathways
      involving the metallochaperones Atxlp and Lys7p. The results indicatethat, in
      addition to the well known Ctr1p and Ctr3p high-affinity copper transporters, the
      metallochaperones can acquire their copper through pathways involving the
      relatively non-specific divalent metal ion transporter Fet4p and the putative low
      affinitycopper transporter Ctr2p. We have examined the localization of Ctr2p
      using an epitope tagged version of the protein and find that Ctr2p does not
      localize to the cell surface but may operate at the level of the vacuole to
      mobilize intracellular copper. Inaddition to Ctrlp, Ctr2p, Ctr3p and Fet4p, other
      metal transport systems can act as upstream donors of copper for the
      metallochaperones when copper availability in the medium is increased. Although
      the nature of these auxiliary systems is unknown, they do not appear to involve
      the yeast members of the Nramp family of divalent transporters, or uptake
      mechanisms that involve endocytosis. Since vastly different metal transporters
      located at either the cell surface or intracellular sites can all contribute
      copper to metallochaperones, it is unlikely that the metallochaperones directly
      interact with the metal transporters to obtain the metal.

PMID- 11523805
TI  - A family of DNA repeats in Aspergillus nidulans has assimilated degenerated
      retrotransposons.
AB  - In the course of a chromosomal walk towards the centromere of chromosome IV of
      Aspergillus nidulans, several cross-hybridizing genomic cosmid clones were
      isolated. Restriction mapping of two such clones revealed that their restriction
      patterns were similar in a region of at least 15 kb, indicating the presence of a
      large repeat. The nature of the repeat was further investigated by sequencing and
      Southern analysis. The study revealed a family of long dispersed repeats with a
      high degree of sequence similarity. The number and location of the repeats vary
      between wild isolates. Two copies of the repeat contained degenerated long
      terminal-repeat (LTR) retrotransposons, which were named Dane1 and Dane2 (for
      Degenerated Aspergillus nidulans element). The pattern of degeneration suggested
      that a process similar to the repeat-induced point-mutation (RIP) phenomenon,
      first described in Neurospora crassa, may have operated in A. nidulans. The data
      indicate that this family of repeats has assimilated mobile elements that
      subsequently degenerated but then underwent further duplications as a part of the
      host repeats.

PMID- 11523806
TI  - The flanking regions of PsaD drive efficient gene expression in the nucleus of
      the green alga Chlamydomonas reinhardtii.
AB  - The nuclear gene PsaD encodes an abundant chloroplast protein located on the
      stromal side of the Photosystem I complex. We have cloned and sequenced a genomic
      fragment containing the PsaD gene from the green alga Chlamydomonas reinhardtii.
      Sequence comparison with its cDNA revealed that the PsaD ORF contains no introns.
      Thus, the regulatory sequences required for high-level expression of PsaD must
      lie in the flanking promoter and untranslated regions. We used this genomic
      fragment to construct a vector that allows for high-level expression of
      endogenous and exogenous genes, as well as cDNAs that could not be expressed from
      existing vectors. It is also possible to use the PsaD transit sequence to target
      the expressed protein to the chloroplast compartment.

PMID- 11523807
TI  - Regulation of tRNA5Leu-encoding gene leuX that is associated with a pathogenicity
      island in the uropathogenic Escherichia coli strain 536.
AB  - Pathogenicity islands (PAls) contain virulence determinants and are often linked
      to tRNA loci. The leuX gene encoding tRNA5Leu is associated with PAI II536 of the
      uropathogenic E. coli strain 536 (O6:K15:H31) and is important for the expression
      of virulence factors in this strain. Transcription of leuX differs from that of
      the majority of tRNA genes including the major leucyl-tRNA gene leuV.
      Availability of the tRNAsLeu can be linked with the efficient expression of
      virulence determinants. Transcription of leuX and letV was studied to gain
      further insights into the regulation of this tRNA gene and its role during the
      expression of virulence determinants. leuX but not letV transcripts accumulated
      in stationary phase. While leuX transcription was unchanged or slightly up
      regulated by an increase in growth temperature, osmolarity or ethanol
      concentration, that of leuV was reduced. The heat shock-specific sigma factor
      RpoH was shown to affect transcription of leuX but not of leuV. These results
      demonstrate that transcription of a tRNA gene can be specifically influenced by
      an alternative sigma factor. Our finding expands our knowledge of the regulation
      of tRNA gene transcription and represents an additional mode of regulation of
      gene expression that can also affect bacterial virulence.

PMID- 11523808
TI  - Transcriptional profile of Toxoplasma gondii-infected human fibroblasts as
      revealed by gene-array hybridization.
AB  - To investigate the host-cell response to infection with the obligate
      intracellular pathogen Toxoplasma gondii, the transcriptional profiles of
      infected and uninfected human fibroblasts (HFF) were determined by hybridization
      to gene arrays representing nearly 600 genes. Transcripts that displayed a
      greater than five-fold increase in level relative to uninfected controls were
      also examined by RT-PCR and Northern analysis, resulting in the identification of
      13 genes that were strongly up-regulated after infection with T. gondii.
      Comparisons with the transcriptional profiles of fibroblasts infected with
      Salmonella typhimurium and Chlamydia trachomatis allowed the identification of
      genes which are specifically induced in T. gondii-infected cells. While most of
      the up-regulated genes were induced on infection with all three pathogens, the
      genes for the transferrin receptor and MacMARCKS were up-regulated in Toxoplasma
      infected fibroblasts only. Expression of the transferrin receptor protein was
      examined by Western analysis and found to be specifically elevated in Toxoplasma
      infected fibroblasts. Genes which are specifically induced in T. gondii-infected
      cells are particularly interesting for further studies, since they might be used
      to dissect specific interactions of this pathogenic parasite with its host cell.

PMID- 11523809
TI  - Functional cloning of an endo-arabinanase from Aspergillus aculeatus and its
      heterologous expression in A. or oryzae and tobacco.
AB  - Functional cloning in yeast has been used to isolate full-length cDNAs encoding
      an endo-alpha-1,5-L-arabinanase from the filamentous fungus Aspergillus
      aculeatus. Screening of a cDNA library constructed in a yeast expression vector
      for transformants that hydrolysed AZCL-arabinan identified 44 Saccharomyces
      cerevisiae clones all harbouring the same arabinanase-encoding cDNA. The cloned
      cDNA was expressed in A. oryzae and the recombinant enzyme was purified and
      characterized. The mode of action of the enzyme was studied by analysis of the
      digestion pattern towards debranched arabinan. The digestion profile obtained
      strongly suggests that the enzyme is an endo-arabinanase. In addition, the
      feasibility using Nicotiana tabacum as an alternative host for arabinanase
      expression was investigated.

PMID- 11523810
TI  - Pantothenate synthetase from Fusarium oxysporum f. sp. lycopersici is induced by
      alpha-tomatine.
AB  - The steroidal glycoalkaloid alpha-tomatine which is present in tomato
      (Lycopersicum sculentum) is assumed to protect the plant against phytopathogenic
      fungi. We have isolated a gene from the fungal pathogen Fusarium oxysporum f. sp.
      lycopersici that is induced by this glycoalkaloid. This gene, designated panC,
      encodes a predicted protein with a molecular mass of 41 kDa that shows a high
      degree of sequence similarity to pantothenate synthetases from yeast, plants and
      bacteria. Recombinant PanC protein from F. oxysporum has been over-expressed in
      Escherichia coli and purified to homogeneity. It shows pantothenate synthetase
      activity in the presence of D-pantoate, beta-alanine and ATP. The panC gene from
      F. oxysporum functionally complements an E. coli panC mutant, demonstrating that
      the PanC protein functions in vivo as a pantothenate synthetase. Southern
      analysis of F. oxysporum genomic DNA from other formae speciales indicates that
      there is a single copy of the pantothenate syntethase gene in this fungus. The
      presence of a STRE consensus sequence (CCCCT) in the promoter region of the gene
      suggests that the induction of panC may be part of a cellular stress response
      triggered by alpha-tomatine.

PMID- 11523811
TI  - Functional cloning, based on azole resistance in Saccharomyces cerevisiae, and
      characterization of Rhizopus nigricans redox carriers that are differentially
      involved in the P450-dependent response to progesterone stress.
AB  - The filamentous fungus Rhizopus nigricans responds to treatment with progesterone
      by inducing P450-associated redox carriers. Selection for azole resistance
      following expression of a cDNA library constructed with RNA from progesterone
      treated R. nigricans in the yeast Saccharomyces cerevisiae led to the
      identification of CPR1-FL and CYB5-1 cDNAs, which code for functionally competent
      NADPH-cytochrome P450 reductase and cytochrome b5, respectively. The central
      region (CPR2-CS) of an additional reductase gene sharing 66% identity with CPR1
      FL was cloned from progesterone-induced mRNA by RT-PCR, using primers based on
      consensus sequences. Northern analysis of the 2.1-kb transcripts revealed that,
      of the two cloned reductase genes, only CPR1-FL mRNA was strongly induced by
      progesterone; transcription of CYBS-1 and CPR2-CS mRNAs was not significantly
      affected. Analysis of the subcellular localization and function of the R.
      nigricans reductase in yeast indicated that the CPR1-FL cDNA and a derivative
      (CPR1-S) truncated at the first ATG codon gave rise to functionally equivalent
      products that were found in both cytosolic and microsomal fractions. In contrast,
      addition of an in-frame initiation codon at the 5' end of the CPR1-FL sequence
      resulted in localization of the activity mainly to the microsomes, and improved
      ketoconazole resistance but decreased NADPH-cytochrome c reductase activity in
      the host strain. These findings suggest that, of the three genes for P450
      associated redox carriers investigated, only CPR1-FL is associated with the
      progesterone response and that its major transcript encodes a reductase that
      shows an unusual pattern of subcellular localization.

PMID- 11523812
TI  - Neural crest patterning and the evolution of the jaw.
AB  - Here we present ideas connecting the behaviour of the cranial neural crest during
      development with the venerable, perhaps incorrect, view that gill-supporting
      cartilages of an ancient agnathan evolved into the skeleton of an early
      gnathostome's jaw. We discuss the pattern of migration of the cranial neural
      crest ectomesenchyme in zebrafish, along with the subsequent arrangement of
      postmigratory crest and head mesoderm in the nascent pharyngeal segments
      (branchiomeres), in diverse gnathostomes and in lampreys. These characteristics
      provide for a plausible von Baerian explanation for the problematic inside
      outside change in topology of the gills and their supports between these 2 major
      groups of vertebrates. We consider it likely that the jaw supports did indeed
      arise from branchiomeric cartilages.

PMID- 11523813
TI  - Early development of the neural plate, neural crest and facial region of
      marsupials.
AB  - Marsupial mammals have a distinctive reproductive strategy. The young are born
      after an exceptionally short period of organogenesis and are consequently
      extremely altricial. Yet because they must be functionally independent in an
      essentially embryonic condition, the marsupial neonate exhibits a unique suite of
      adaptations. In particular, certain bones of the facial region, most cranial
      musculature and a few additional structures are accelerated in their development.
      In contrast, central nervous system structures, especially the forebrain, are
      markedly premature at birth, resembling an embryonic d 11 or 12 mouse. This
      review examines the developmental processes that are modified to produce these
      evolutionary changes. The focus is on the early development of the neural plate,
      neural crest and facial region in the marsupial, Monodelphis domestica, compared
      with patterns reported for rodents. Neural crest begins differentiation and
      migration at the neural plate stage, which results in large accumulations of
      neural crest in the facial region at an early stage of development. The early
      accumulation of neural crest provides the material for the accelerated
      development of oral and facial structures. The first arch region is massive in
      the early embryo, and the development of the olfactory placode and frontonasal
      region is advanced relative to the forebrain region. The development of the
      forebrain is delayed in marsupials relative to the hindbrain or facial region.
      These observations illustrate how development may be modified to produce
      evolutionary changes that distinguish taxa. Further, they suggest that
      development is not necessarily highly conserved, but instead may be quite
      plastic.

PMID- 11523814
TI  - Beyond the Hox: how widespread is homeobox gene clustering?
AB  - The arrangement of Hox genes into physical clusters is fundamental to the
      patterning of animal body plans, through the phenomenon of colinearity. Other
      homeobox genes are often described as dispersed, implying they are not arranged
      into clusters. Contrary to this view, however, two clusters of non-Hox homeobox
      genes have been reported: the amphioxus ParaHox gene cluster and the Drosophila
      93D/E cluster (referred to here as the NKL cluster). Here I examine the antiquity
      of these gene clusters, their conservation and their pattern of evolution in
      vertebrate genomes. I argue that the ParaHox gene cluster arose early in animal
      evolution, and duplicated in vertebrates to give the four clusters in human and
      mouse genomes. The NKL cluster is also ancient, and also duplicated to yield four
      descendent clusters in mammalian genomes. The NKL and Hox gene clusters were
      originally chromosomal neighbours, within an ancient and extensive array of at
      least 30 related homeobox genes. There is no necessary relationship between
      clustering and colinearity, although it is argued that the ParaHox gene cluster
      does show modified spatial colinearity. A novel hypothesis for the evolution of
      ParaHox gene expression in deuterostomes is presented.

PMID- 11523815
TI  - The development and evolution of the pharyngeal arches.
AB  - A muscularised pharynx, with skeletal support, serving the dual functions of
      feeding and respiration, is a fundamental vertebrate characteristic.
      Embryologically, the pharyngeal apparatus has its origin in a series of bulges
      that form on the lateral surface of the embryonic head, the pharyngeal arches,
      whose development is complex. These structures are composed of a number of
      disparate embryonic cell types: ectoderm, endoderm, neural crest and mesoderm,
      whose development must be coordinated to generate the functional adult apparatus.
      In the past, most studies have emphasised the role played by the neural crest,
      which generates the skeletal elements of the arches, in directing pharyngeal arch
      development, but it has also become apparent that the endoderm plays a prominent
      role in directing arch development. Neural crest cells are not required for arch
      formation, their regionalisation nor to some extent their sense of identity.
      Furthermore, the endoderm is the major site of expression of a number of
      important signalling molecules, and this tissue has been shown to be responsible
      for promoting the formation of particular components of the arches. Thus
      vertebrate pharyngeal morphogenesis can now be seen to be a more complex process
      than was previously believed, and must result from an integration of both neural
      crest and endodermal patterning mechanisms. Interestingly, this also mirrors the
      fact that the evolutionary origin of pharyngeal segmentation predates that of the
      neural crest, which is an exclusively vertebrate characteristic. As such, the
      evolution of the vertebrate pharynx is also likely to have resulted from an
      integration between these 2 patterning systems. Alterations in the interplay
      between neural crest and endodermal patterning are also likely to be responsible
      for the evolutionary that occurred to the pharyngeal region during subsequent
      vertebrate evolution.

PMID- 11523816
TI  - Derivation of the mammalian skull vault.
AB  - This review describes the evolutionary history of the mammalian skull vault as a
      basis for understanding its complex structure. Current information on the
      developmental tissue origins of the skull vault bones (mesoderm and neural crest)
      is assessed for mammals and other tetrapods. This information is discussed in the
      context of evolutionary changes in the proportions of the skull vault bones at
      the sarcopterygian-tetrapod transition. The dual tissue origin of the skull vault
      is considered in relation to the molecular mechanisms underlying osteogenic cell
      proliferation and differentiation in the sutural growth centres and in the
      proportionate contributions of different sutures to skull growth.

PMID- 11523817
TI  - Evolution and development of teeth.
AB  - Teeth as a feeding mechanism in an oral cavity (mouth) are functionally and
      locationally linked with jaws. In fossils, teeth found in the oral cavity are
      usually linked with jaws, although mineralised structures with the same histology
      as teeth are known in fossils before jaws appeared. Denticles in the skin occur
      in both fossil and extant fish. Pharyngeal denticles also occur in both extant
      and fossil gnathostomes but in only a few fossil agnathans (thelodonts). Complex
      structures with dentine and enamel have been described in the earliest jawless
      vertebrates, conodonts. Such fossils have been used to suggest that teeth and
      jaws have evolved and developed independently. Our understanding of the
      developmental biology of mammalian tooth development has increased greatly in the
      last few years to a point where we now understand some of the basic genetic
      interactions controlling tooth initiation, morphogenesis and patterning. The aim
      of this review is to see what this developmental information can reveal about
      evolution of the dentition.

PMID- 11523818
TI  - Conserved developmental processes constrain evolution of lungfish dentitions.
AB  - Although the 3 genera of living lungfish have different-shaped adult tooth
      plates, their larval stages have similar patterns of development. The sequence in
      the pattern of initiation of teeth and their modification through ontogeny in
      Neoceratodus hatchlings provides a developmental model for fossil hatchling tooth
      plates (smallest 1-2 mm) recovered as 3-dimensional dentitions from
      Andreyevichthys. This Late Devonian lungfish demonstrates that these also have a
      similar dentition pattern and suggests strongly conserved developmental
      processes. We postulate that a specific pattern of development, derived within
      lungfish, has been conserved in extant forms through evolution from the earliest
      known lungfish. The most basal early dipnoan, Diabolepis speratus, is also known
      from juveniles with tooth plates formed in this pattern. The lungfish pattern is
      in marked contrast to the typical linear rows of teeth with lingual replacement
      for each tooth position, characteristic of most osteichthyan and chondrichthyan
      dentitions. Uniquely for lungfish, teeth are only added to the lateral ends of
      the radial rows in the palatal and lingual dentition and are consolidated into
      dental plates without loss through shedding. It is proposed that this tooth
      pattern is set up from primordial teeth at the patterning stage of the dentition,
      one in each dentate region of the larval jaws. Although in post-Devonian lungfish
      marginal dentate bones are absent in the adult, in both the fossil and extant
      hatchling, teeth are present and function on some of the marginal bones. This
      pattern of development and loss is described and we conclude that in both forms
      it is also based on a radial pattern of successive tooth initiation. We propose
      that this ontogenetic pattern constrained the phylogenetic pattern of adult form,
      through evolution of dipnoan dentitions from 360 MYBP until the present. The
      universality amongst dipnoans and the implications for such a conserved
      constraint in the developmental module for the dentition is discussed.

PMID- 11523819
TI  - The vertebrate segmentation clock.
AB  - Vertebrate somitogenesis has been shown to be associated with a molecular
      oscillator, the segmentation clock, whose periodicity matches that of the process
      of somitogenesis. The existence of such a clock in presomitic mesoderm (PSM)
      cells was originally proposed in theoretical models such as the 'clock and
      wavefront'. Molecular evidence for the existence of this clock in vertebrates has
      been obtained on the basis of the periodic expression of several genes, most of
      which are related to the Notch signalling pathway. These genes are expressed in a
      dynamic sequence which appears as a wave sweeping caudo-rostrally along the whole
      PSM once during each somite formation. Notch-pathway mouse and fish mutants lose
      the dynamic expression of the cycling genes, indicating that Notch signalling is
      required for their periodic expression, or is required to coordinate the
      oscillations between PSM cells. Therefore Notch signalling is either part of the
      mechanism of the oscillator itself or acts as a cofactor required for cycling
      gene expression. A further potentially important role for the segmentation clock
      is to periodically activate Notch signalling in the rostral presomitic mesoderm,
      thereby generating the periodic formation of somite boundaries.

PMID- 11523820
TI  - The role of the notochord in vertebral column formation.
AB  - The backbone or vertebral column is the defining feature of vertebrates and is
      clearly metameric. Given that vertebrae arise from segmented paraxial mesoderm in
      the embryo, this metamerism is not surprising. Fate mapping studies in a variety
      of species have shown that ventromedial sclerotome cells of the differentiated
      somite contribute to the developing vertebrae and ribs. Nevertheless, extensive
      studies in amniote embryos have produced conflicting data on exactly how
      embryonic segments relate to those of the adult. To date, much attention has
      focused on the derivatives of the somites, while relatively little is known about
      the contribution of other tissues to the formation of the vertebral column. In
      particular, while it is clear that signals from the notochord induce and maintain
      proliferation of the sclerotome, and later promote chondrogenesis, the role of
      the notochord in vertebral segmentation has been largely overlooked. Here, we
      review the established role of the notochord in vertebral development, and
      suggest an additional role for the notochord in the segmental patterning of the
      vertebral column.

PMID- 11523821
TI  - The role of Bapx1 (Nkx3.2) in the development and evolution of the axial
      skeleton.
AB  - The bagpipe-related homeobox-containing genes are members of the NK family,
      bagpipe (bap) was first identified in Drosophila and there are three different
      bagpipe-related genes in vertebrates. Only two of these are found in mammals, the
      Nkx3.1 and the Bapxl (Nkx3.2) gene. The targeted mutation in the mouse Bapxl gene
      shows a vertebral phenotype in which the ventromedial elements are lacking; these
      are the centra and the intervertebral discs. In addition, a region of gastric
      mesenchyme is abnormal. This mesenchyme surrounds the posterior region of the
      presumptive stomach and duodenum, and in the mutant fails to support normal
      development of the spleen. In Drosophila, bagpipe has a role in gut mesoderm and
      the mutant embryos have no midgut musculature. Thus bap related genes in mouse
      and Drosophila have roles in patterning gut mesoderm; however, neither of the
      mammalian genes has a discernible role in the gut musculature. In contrast, both
      mammalian genes have roles in developmental processes that have appeared recently
      in evolution. The Bapxl gene found in fish, amphibians, birds and mammals appears
      to have derived vertebrate specific functions sometime after the split between
      the jawless fish and gnathostomes.

PMID- 11523822
TI  - The evolution of the pectoral girdle.
AB  - The pectoral girdle articulates the forelimb with the axial skeleton in all
      vertebrates with paired anterior appendages. The structure of the pectoral girdle
      and its position along the axial skeleton has changed significantly during
      vertebrate evolution. These morphological changes have been well described, but
      there is little comparative embryology to indicate how these changes may have
      occurred. It is equally obscure how the muscles that connect the head with the
      pectoral girdle have maintained appropriate attachments even though these 2
      structures have become separated. Here I review the changes in the pectoral
      girdle across different vertebrate taxa, indicating, where known, the
      developmental mechanisms underlying these changes. I also suggest how the
      muscular connections between the head and pectoral girdle have been maintained
      between these once adjacent bones, displaced during vertebrate evolution.

PMID- 11523823
TI  - Evolutionary aspects of positioning and identification of vertebrate limbs.
AB  - Emerging developmental studies contribute to our understanding of vertebrate
      evolution because changes in the developmental process and the genes responsible
      for such changes provide a unique way for evaluating the evolution of morphology.
      Endoskeletal limbs, the locomotor organs that are unique to vertebrates, are a
      popular model system in the fields of palaeontology and phylogeny because their
      structure is highly visible and their bony pattern is easily preserved in the
      fossil records. Similarly, limb development has long served as an excellent model
      system for studying vertebrate pattern formation. In this review, the evolution
      of vertebrate limb development is examined in the light of the latest knowledge,
      viewpoints and hypotheses.

PMID- 11523824
TI  - Morphogenesis and evolution of vertebrate appendicular muscle.
AB  - Two different modes are utilised by vertebrate species to generate the
      appendicular muscle present within fins and limbs. Primitive Chondricthyan or
      cartilaginous fishes use a primitive mode of muscle formation to generate the
      muscle of the fins. Direct epithelial myotomal extensions invade the fin and
      generate the fin muscles while remaining in contact with the myotome. Embryos of
      amniotes such as chick and mouse use a similar mechanism to that deployed in the
      bony teleost species, zebrafish. Migratory mesenchymal myoblasts delaminate from
      fin/limb level somites, migrate to the fin/limb field and differentiate entirely
      within the context of the fin/limb bud. Migratory fin and limb myoblasts express
      identical genes suggesting that they possess both morphogenetic and molecular
      identity. We conclude that the mechanisms controlling tetrapod limb muscle
      formation arose prior to the Sarcopterygian or tetrapod radiation.

PMID- 11523825
TI  - The development and evolution of crossveins in insect wings.
AB  - The formation of crossveins in Drosophila was an important early case study in
      understanding the role of the environment in the development and evolution of
      morphological structures. More recent work has shown that signalling processes
      play a crucial role in the formation of crossveins in Drosophila and that the
      interaction of a heat shock factor, Hsp90, with components of signal transduction
      pathways may account for the sensitivity of these structures to environmental
      perturbations. A new model for the development of crossveins is presented that
      divides the formation of crossveins into 3 separate stages. First, the number and
      placement of the crossveins is determined by signalling along the proximal-distal
      axis of the wing. This signal may involve the cdc42 gene product and the Jun-N
      terminal Kinase signal transduction pathway. Then, during the second stage, an
      inductive signal from the dorsal wing epithelium is sent to the ventral wing
      epithelium at locations specified by the first signal. The second signal appears
      to involve the BMP-like signalling pathway. Finally, in the third stage, a domain
      of vein competent cells is defined by the signalling from the EGF-receptor-Map
      Kinase signal transduction pathway, and the exact location of the veins is
      eventually determined within that domain by Notch-Delta signalling interactions.
      By altering components of these 3 stages, insects can independently regulate the
      presence or absence, the number and placement, and the thickness and flexibility
      of the crossveins. This capacity for the modulation of crossvein structure in
      many different ways may have contributed to the evolution of different modes of
      insect flight.

PMID- 11523826
TI  - Insect oenocytes: a model system for studying cell-fate specification by Hox
      genes.
AB  - During insect development, morphological differences between segments are
      controlled by the Hox gene family of transcription factors. Recent evidence also
      suggests that variation in the regulatory elements of these genes and their
      downstream targets underlies the evolution of several segment-specific
      morphological traits. This review introduces a new model system, the larval
      oenocyte, for studying the evolution of fate specification by Hox genes at single
      cell resolution. Oenocytes are found in a wide range of insects, including
      species using both the short and the long germ modes of development. Recent
      progress in our understanding of the genetics and cell biology of oenocyte
      development in the fruitfly Drosophila melanogaster is discussed. In the D.
      melanogaster embryo, the formation of this cell type is restricted to the first 7
      abdominal segments and is under Hox gene control. Oenocytes delaminate from the
      dorsal ectoderm of A1-A7 in response to an induction that involves the epidermal
      growth factor receptor (EGFR) signalling pathway. Although the receptor itself is
      required in the presumptive oenocytes, its ligand Spitz (Spi) is secreted by a
      neighbouring chordotonal organ precursor (COP). Thus, in dorsal regions, local
      signalling from this component of the developing peripheral nervous system
      induces the formation of oenocytes. In contrast, in lateral regions of the
      ectoderm, Spi signal from a different COP induces the formation of secondary COPs
      in a homeogenetic manner. This dorsoventral difference in the fate induced by Spi
      ligand is controlled by a prepattern in the responding ectoderm that requires the
      Spalt (Sal) transcription factor. Sal protein is expressed in the dorsal but not
      lateral ectoderm and acts as a competence modifier to bias the response to Spi
      ligand in favour of the oenocyte fate. We discuss a recently proposed model that
      integrates the roles of Sal and the EGFR pathway in oenocyte/chordotonal organ
      induction. This model should provide a useful starting point for future
      comparative studies of these ectodermal derivatives in other insects.

PMID- 11523827
TI  - Regeneration as an evolutionary variable.
AB  - Regeneration poses a distinctive set of problems for evolutionary biologists, but
      there has been little substantive progress since these issues were clearly
      outlined in the monograph of T. H. Morgan (1901). The champions at regeneration
      among vertebrates are the urodele amphibians such as the newt, and we tend to
      regard urodele regeneration as an exceptional attribute. The ability to
      regenerate large sections of the body plan is widespread in metazoan phylogeny,
      although it is not universal. It is striking that in phylogenetic contexts where
      regeneration occurs, closely related species are observed which do not possess
      this ability. It is a challenge to reconcile such variation between species with
      a conventional selective interpretation of regeneration. The critical hypothesis
      from phylogenetic analysis is that regeneration is a basic, primordial attribute
      of metazoans rather than a mechanism which has evolved independently in a variety
      of contexts. In order to explain its absence in closely related species, it is
      postulated to be lost secondarily for reasons which are not understood. Our
      approach to this question is to compare a differentiated newt cell with its
      mammalian counterpart in respect of the plasticity of differentiation.

PMID- 11523828
TI  - Evolution of vertebrate forebrain development: how many different mechanisms?
AB  - Over the past 50 years and more, many models have been proposed to explain how
      the nervous system is initially induced and how it becomes subdivided into gross
      regions such as forebrain, midbrain, hindbrain and spinal cord. Among these
      models is the 2-signal model of Nieuwkoop & Nigtevecht (1954), who suggested that
      an initial signal ('activation') from the organiser both neuralises and specifies
      the forebrain, while later signals ('transformation') from the same region
      progressively caudalise portions of this initial territory. An opposing idea
      emerged from the work of Otto Mangold (1933) and other members of the Spemann
      laboratory: 2 or more distinct organisers, emitting different signals, were
      proposed to be responsible for inducing the head, trunk and tail regions. Since
      then, evidence has accumulated that supports one or the other model, but it has
      been very difficult to distinguish between them. Recently, a considerable body of
      work from mouse embryos has been interpreted as favouring the latter model, and
      as suggesting that a 'head organiser', required for the induction of the
      forebrain, is spatially separate from the classic organiser (Hensen's node). An
      extraembryonic tissue, the 'anterior visceral endoderm' (AVE), was proposed to be
      the source of forebrain-inducing signals. It is difficult to find tissues that
      are directly equivalent embryologically or functionally to the AVE in other
      vertebrates, which led some (e.g. Kessel, 1998) to propose that mammals have
      evolved a new way of patterning the head. We will present evidence from the chick
      embryo showing that the hypoblast is embryologically and functionally equivalent
      to the mouse AVE. Like the latter, the hypoblast also plays a role in head
      development. However, it does not act like a true organiser. It induces pre
      neural and pre-forebrain markers, but only transiently. Further development of
      neural and forebrain phenotypes requires additional signals not provided by the
      hypoblast. In addition, the hypoblast plays a role in directing cell movements in
      the adjacent epiblast. These movements distance the future forebrain territory
      from the developing organiser (Hensen's node), and we suggest that this is a
      mechanism to protect the forebrain from caudalising signals from the node. These
      mechanisms are consistent with all the findings obtained from the mouse to date.
      We conclude that the mechanisms responsible for setting up the forebrain and more
      caudal regions of the nervous system are probably similar among different classes
      of higher vertebrates. Moreover, while reconciling the two main models, our
      findings provide stronger support for Nieuwkoop's ideas than for the concept of
      multiple organisers, each inducing a distinct region of the CNS.

PMID- 11523829
TI  - Otx genes in evolution: are they involved in instructing the vertebrate brain
      morphology?
AB  - Previous mouse models have indicated that Otx1 and Otx2 play an important role in
      brain and sense organ development and, together with the Drosophila orthodenticle
      (otd) gene, they share a high degree of reciprocal functional equivalence.
      Interestingly, mouse models replacing the same region of the Otx2 locus with
      Otx1, otd or lacZ genes have revealed the existence of a differential post
      transcriptional control between the visceral endoderm (VE) and epiblast cells.
      Indeed Otx1, otd or lacZ mRNA were transcribed in both tissues but translated
      only in the VE. Embryos lacking OTX1 or OTD proteins in the epiblast and derived
      tissues, such as the neuroectoderm and axial mesendoderm (AME), fail to maintain
      the anterior identity and result in a headless phenotype. This finding leads us
      to hypothesise that, during evolution, the specification of the vertebrate-type
      brain may have required epiblast cells to translate Otx2 mRNA in order to
      establish maintenance properties. The establishment of this regulatory control
      might have been reflected into a remarkable reorganisation of the rostral CNS
      architecture and might have represented an important event in the evolution of
      the vertebrate head. Current data suggest that the Otx2 replaced region and in
      particular the 3' untranslated region (UTR), may contain regulatory element(s)
      necessary to translate and/or stabilise Otx2 mRNA in epiblast and its
      derivatives.

PMID- 11523831
TI  - Evolution of neural crest and placodes: amphioxus as a model for the ancestral
      vertebrate?
AB  - Recent studies of protochordates (ascidian tunicates and amphioxus) have given
      insights into possible ancestors of 2 of the characteristic features of the
      vertebrate head: neural crest and placodes. The neural crest probably evolved
      from cells on either side of the neural plate-epidermis boundary in a
      protochordate ancestral to the vertebrates. In amphioxus, homologues of several
      vertebrate neural crest marker genes (BMP2/4, Pax3/7, Msx, Dll and Snail) are
      expressed at the edges of the neural plate and/or adjacent nonneural ectoderm.
      Some of these markers are also similarly expressed in tunicates. In
      protochordates, however, these cells, unlike vertebrate neural crest, neither
      migrate as individuals through embryonic tissues nor differentiate into a wide
      spectrum of cell types. Therefore, while the protochordate ancestor of the
      vertebrates probably had the beginnings of a genetic programme for neural crest
      formation, this programme was augmented in the earliest vertebrates to attain
      definitive neural crest. Clear homologues of vertebrate placodes are lacking in
      protochordates. However, both amphioxus and tunicates have ectodermal sensory
      cells. In tunicates these are all primary neurons, sending axons to the central
      nervous system, while in amphioxus, the ectodermal sensory cells include both
      primary neurons and secondary neurons lacking axons. Comparisons of developmental
      gene expression suggest that the anterior ectoderm in amphioxus may be homologous
      to the vertebrate olfactory placode, the only vertebrate placode with primary,
      not secondary, neurons. Similarly, biochemical, morphological and gene expression
      data suggest that amphioxus and tunicates also have homologues of the
      adenohypophysis, one of the few vertebrate structures derived from nonneurogenic
      placodes. In contrast, the origin of the other vertebrate placodes is very
      uncertain.

PMID- 11523832
TI  - Origin of the vertebrate inner ear: evolution and induction of the otic placode.
AB  - The vertebrate inner ear forms a highly complex sensory structure responsible for
      the detection of sound and balance. Some new aspects on the evolutionary and
      developmental origin of the inner ear are summarised here. Recent molecular data
      have challenged the longstanding view that special sense organs such as the inner
      ear have evolved with the appearance of vertebrates. In addition, it has remained
      unclear whether the ear originally arose through a modification of the amphibian
      mechanosensory lateral line system or whether both evolved independently. A
      comparison of the developmental mechanisms giving rise to both sensory systems in
      different species should help to clarify some of these controversies. During
      embryonic development, the inner ear arises from a simple epithelium adjacent to
      the hindbrain, the otic placode, that is specified through inductive interactions
      with surrounding tissues. This review summarises the embryological evidence
      showing that the induction of the otic placode is a multistep process which
      requires sequential interaction of different tissues with the future otic
      ectoderm and the recent progress that has been made to identify some of the
      molecular players involved. Finally, the hypothesis is discussed that induction
      of all sensory placodes initially shares a common molecular pathway, which may
      have been responsible to generate an 'ancestral placode' during evolution.

PMID- 11523830
TI  - Asymmetry in the epithalamus of vertebrates.
AB  - The epithalamus is a major subdivision of the diencephalon constituted by the
      habenular nuclei and pineal complex. Structural asymmetries in this region are
      widespread amongst vertebrates and involve differences in size. neuronal
      organisation, neurochemistry and connectivity. In species that possess a
      photoreceptive parapineal organ, this structure projects asymmetrically to the
      left habenula, and in teleosts it is also situated on the left side of the brain.
      Asymmetries in size between the left and right sides of the habenula are often
      associated with asymmetries in neuronal organisation, although these two types of
      asymmetry follow different evolutionary courses. While the former is more
      conspicuous in fishes (with the exception of teleosts), asymmetries in neuronal
      organisation are more robust in amphibia and reptiles. Connectivity of the
      parapineal organ with the left habenula is not always coupled with asymmetries in
      habenular size and/or neuronal organisation suggesting that, at least in some
      species, assignment of parapineal and habenular asymmetries may be independent
      events. The evolutionary origins of epithalamic structures are uncertain but
      asymmetry in this region is likely to have existed at the origin of the
      vertebrate, perhaps even the chordate, lineage. In at least some extant
      vertebrate species, epithalamic asymmetries are established early in development,
      suggesting a genetic regulation of asymmetry. In some cases, epigenetic factors
      such as hormones also influence the development of sexually dimorphic habenular
      asymmetries. Although the genetic and developmental mechanisms by which
      neuroanatomical asymmetries are established remain obscure, some clues regarding
      the mechanisms underlying laterality decisions have recently come from studies in
      zebrafish. The Nodal signalling pathway regulates laterality by biasing an
      otherwise stochastic laterality decision to the left side of the epithalamus.
      This genetic mechanism ensures a consistency of epithalamic laterality within the
      population. Between species, the laterality of asymmetry is variable and a clear
      evolutionary picture is missing. We propose that epithalamic structural
      asymmetries per se and not the laterality of these asymmetries are important for
      the behaviour of individuals within a species. A consistency of the laterality
      within a population may play a role in social behaviours between individuals of
      the species.

PMID- 11523833
TI  - Academic achievement of low birthweight children at age 11: the role of cognitive
      abilities at school entry.
AB  - We examine the extent to which deficits in academic achievement in low
      birthweight (LBW) children at age 11 are explained by deficits in cognitive
      abilities at school entry. Data come from a longitudinal study of a stratified
      sample of LBW and normal birthweight (NBW) children from an innercity and middle
      class suburbs in the Detroit area. Woodcock-Johnson Psychoeducational Battery
      Revised was used to measure reading and math at age 11. WISC-R and specific
      neuropsychologic tests were administered at age 6. On reading, the LBW-NBW
      difference was -3.6 points (SE = 1.2). The difference was explained almost
      entirely by IQ at age 6. On math, the LBW-NBW difference was -6.1 points (SE =
      1.1). The difference on math was trivial and not significant, when IQ and
      neuropsychological tests at age 6 were controlled. Level of LBW was unrelated to
      reading, but it had a gradient relationship with math, with birthweight < or =
      1,500 g associated with a greater deficit than heavier LBW. The results imply
      that most of the LBW-NBW gap in academic achievement at age 11 could be
      eliminated by eliminating differences in cognitive abilities at age 6.
      Interventions to improve academic performance of LBW children should focus on the
      preschool years.

PMID- 11523834
TI  - Low self-esteem and hopelessness in childhood and suicidal ideation in early
      adulthood.
AB  - This study examined the longitudinal relationship between family characteristics
      in early childhood. self-esteem, hopelessness and thoughts of self-harm in the
      midchildhood years, and suicidal ideation at ages 18 and 21. Path analysis was
      used to establish separate models for boys and girls. The results suggested
      different pathways to later suicidal ideation for boys and girls. For boys,
      suicidal ideation seemed to have stronger roots in childhood, with significant
      paths from low self-esteem and hopelessness to early thoughts of self-harm and
      thence to later ideation. For girls, self-esteem had a small but significant
      direct effect on later suicidal ideation. The findings provide support for the
      idea that individual characteristics such as feelings of hopelessness and low
      self-esteem act as "generative mechanisms," linking early childhood family
      characteristics to suicidal ideation in early adulthood.

PMID- 11523835
TI  - Reactive and proactive aggression: predictions to physical violence in different
      contexts and moderating effects of parental monitoring and caregiving behavior.
AB  - This study aimed at (a) comparing the links of proactive and reactive aggression
      at 13 years of age to delinquency-related violence and dating violence at ages 16
      and 17, and (b) examining the moderating effects of parental supervision, and
      mother's and father's warmth and caregiving behaviors on these links. Based on a
      sample of 525 Caucasian boys, the results showed that proactive aggression
      uniquely predicted delinquency-related violence, whereas reactive aggression
      uniquely predicted later dating violence. The relation between proactive
      aggression and delinquency-related violence, however, was moderated by parental
      supervision. The relation between reactive aggression and dating violence was
      moderated by mother's warmth and caregiving behavior. The implications of the
      findings for the theoretical and practical distinction between proactive and
      reactive aggression are discussed.

PMID- 11523836
TI  - Childhood and adolescent onset conduct disorder: a test of the developmental
      taxonomy.
AB  - Hypotheses generated by a developmental taxonomy that distinguishes between
      childhood and adolescent onset conduct disorders were tested. Hypotheses
      predicted that (1) individual and familial factors would be more strongly related
      to childhood onset conduct disorder, whereas ethnic minority status and exposure
      to deviant peers would be more strongly related to adolescent onset conduct
      disorder and (2) individuals with childhood onset disorder would be more likely
      to commit violent and victim oriented offenses than individuals with adolescent
      onset conduct disorder. The first hypothesis was strongly supported and the
      second hypothesis was partially supported. Implications for early identification
      of youth at risk for chronic offending are discussed.

PMID- 11523837
TI  - Dynamic analyses of mother-child interactions in functional and dysfunctional
      dyads: a synergetic approach.
AB  - Describes the application of a new analytical approach (derived from synergetics,
      a complex dynamic systems theory) to home observational data of mother-child
      interactions in average dyads and dyads with children referred for disruptive
      behavior problems at home and school (n = 11 in each group). Results show that
      (1) the two groups differed in their daily interactions in predictable ways, and
      (2) the most frequent patterns of interactions observed in the two groups brought
      them back repeatedly to behave in similar ways toward each other. The findings
      are in keeping with a body of literature on mother-child interactions. However,
      they add to it by providing multivariate. graphical representations of these
      interactions and by offering a conceptual framework within which to move from an
      observational to an inferential level of analysis. At that level, the
      transactional processes that are characteristic of functional and dysfunctional
      relationships may become apparent.

PMID- 11523838
TI  - The structure of negative emotions in adolescents.
AB  - This study examined the structure of negative emotions in a sample of nonclinical
      adolescents, using an approach that exclusively relied on child self-report. A
      large sample of adolescents (N = 968) completed self-report questionnaires
      measuring symptoms of fear, anxiety, and depression. Confirmatory factor analysis
      provided support for the notion that fear, anxiety, and depression are distinct
      yet correlated components of negative emotions. This result is in agreement with
      recent empirical findings and current theoretical notions on the structure of
      negative emotions in children and should be taken as an encouragement for
      researchers to develop more specific measures for assessing fear, anxiety, and
      depression in children.

PMID- 11523839
TI  - A confirmatory factor analysis on the DSM-IV ADHD and ODD symptoms: what is the
      best model for the organization of these symptoms?
AB  - Confirmatory factor analysis (CFA) was used to evaluate five different models for
      the organization of the DSM-IV ADHD and oppositional defiant disorder (ODD)
      symptoms (Model 1: a single factor model; Model 2: an ADHD and ODD two factor
      model; Model 3a: an inattention (INA), hyperactivity/impulsivity (HYP/IMP), and
      ODD three factor model; Model 3b: an INA, HYP/IMP, and ODD three factor model
      where the three IMP symptoms cross-load on the ODD factor; Model 4: an INA, HYP,
      IMP, and ODD four factor model). To evaluate these models, maternal ratings of
      ADHD and ODD symptoms were obtained at outpatient pediatric clinics on 742
      children not in treatment and 91 children in treatment for ADHD. Model 3a
      resulted in a good fit as well as a significantly better fit than Model 2. Model
      3a was also equivalent across treatment status, gender, and age groupings for the
      most part. Though Models 3b and 4 provided a statistically better fit than Model
      3a, the improvement in fit was small and other model selection criteria argued
      against these more complex models.

PMID- 11523840
TI  - Effects of methylphenidate on kinematic aspects of handwriting in hyperactive
      boys.
AB  - Poor handwriting in hyperactive children often contributes to academic failure.
      Beneficial effects of methylphenidate on the quality of handwriting have been
      shown. Using a digitizing tablet, the handwriting of 21 hyperactive boys was
      examined both during methylphenidate treatment and following withdrawal of the
      drug. Half of the hyperactive boys were tested first on methylphenidate and then
      following withdrawal of the drug and the remaining hyperactive boys were examined
      in the reverse order. Twenty-one control boys underwent the same examination.
      Velocity and acceleration of handwriting movements were measured. Furthermore,
      every writing specimen was independently rated by four examiners regarding the
      quality of handwriting. Following withdrawal of the drug, the quality of
      handwriting specimens of hyperactive boys was poorer than during treatment with
      methylphenidate. Statistical comparison of writing movements of hyperactive boys
      on and off methylphenidate revealed that the medication resulted in a
      deterioration in handwriting fluency. The results showed that following
      withdrawal of medication, hyperactive children did not differ from control boys
      in handwriting movements. The improvement in hyperactive behavior through
      methylphenidate was associated with increased legibility and greater accuracy of
      handwriting. The intention to write neatly may interfere with the fluent writing
      process.

PMID- 11523841
TI  - Stress and development: biological and psychological consequences.

PMID- 11523842
TI  - Early adverse experience as a developmental risk factor for later
      psychopathology: evidence from rodent and primate models.
AB  - Increasing evidence supports the view that the interaction of perinatal exposure
      to adversity with individual genetic liabilities may increase an individual's
      vulnerability to the expression of psycho- and physiopathology throughout life.
      The early environment appears to program some aspects of neurobiological
      development and, in turn, behavioral, emotional, cognitive, and physiological
      development. Several rodent and primate models of early adverse experience have
      been analyzed in this review, including those that "model" maternal separation or
      loss, abuse or neglect, and social deprivation. Accumulating evidence shows that
      these early traumatic experiences are associated with long-term alterations in
      coping style, emotional and behavioral regulation. neuroendocrine responsiveness
      to stress, social "fitness,' cognitive function, brain morphology,
      neurochemistry, and expression levels of central nervous system genes that have
      been related to anxiety and mood disorders. Studies are underway to identify
      important aspects of adverse early experience, such as (a) the existence of
      "sensitive periods" during development associated with alterations in particular
      output systems. (b) the presence of "windows of opportunity" during which
      targeted interventions (e.g., nurturant parenting or supportive-enriching
      environment) may prevent or reverse dysfunction, (c) the identity of gene
      polymorphisms contributing to the individual's variability in vulnerability, and
      (d) a means to translate the timing of these developmental "sensitive periods"
      across species.

PMID- 11523843
TI  - Effects of early stress on brain structure and function: implications for
      understanding the relationship between child maltreatment and depression.
AB  - Child abuse is associated with markedly elevated rates of major depression (MDD)
      in child, adolescentt, and adult cohorts. This article reviews preclinical (e.g.,
      animal) studies of the effects of early stress and studies of the neurobiological
      correlates of MDD in adults and children, and it highlights differences in the
      neurobiological correlates of MDD and stress at various developmental stages. The
      preclinical studies demonstrate that stress early in life can alter the
      development multiple neurotransmitter systems and promote structural and
      functional alterations in brain regions similar to those seen in adults with
      depression. Preclinical and clinical studies suggest, however, that long-term
      neurobiological changes associated with early stress can be modified by
      familial/genetic factors, the quality of the subsequent caregiving environment,
      and pharmacological interventions. Little is known about how developmental
      factors interact with experiences of early stress and these other modifying
      factors. Moreover, in cases of child maltreatment, the effects of early abuse are
      often exacerbated by failures in the child protection system and repeat out-of
      home placements. Given the number of factors that impact on the long-term outcome
      of maltreated children, multidisciplinary research efforts are recommended to
      address this problem-with foci that span from neurobiology to social policy.

PMID- 11523844
TI  - Stress and development: behavioral and biological consequences.
AB  - Childhood abuse is an important public health problem; however, little is known
      about the effects of abuse on the brain and neurobiological development. This
      article reviews the behavioral and biological consequences of childhood abuse and
      places them in a developmental context. Animal studies show that both positive
      and negative events early in life can influence neurobiological development in
      unique ways. Early stressors such as maternal separation result in lasting
      effects on stress-responsive neurobiological systems, including the hypothalamic
      pituitary-adrenal (HPA) axis and noradrenergic systems. These studies also
      implicate a brain area involved in learning and memory, the hippocampus. in the
      long-term consequences of early stress. Clinical studies of patients with a
      history of abuse also implicate dysfunction in the HPA axis and the noradrenergic
      and hippocampal systems; however, there are multiple questions related to
      chronicity of stress, developmental epoch at the time of the stressor, presence
      of stress-related psychiatric disorders including posttraumatic stress disorder
      and depression. and psychological factors mediating the response to trauma that
      need to be addressed in this field of research. Understanding the effects of
      abuse on the development of the brain and neurobiology will nevertheless have
      important treatment and policy implications.

PMID- 11523845
TI  - Glucocorticoid effects on memory function over the human life span.
AB  - Glucocorticoids (GCs), produced by the stress-responsive hypothalamic-pituitary
      adrenal axis, are well recognized for their regulatory role in peripheral
      metabolism. GCs are also known to regulate various brain functions, with well
      described effects on human cognition. Increased GC exposure in humans-including
      exposure to the endogenous GC, cortisol-at levels associated with stress,
      decreases memory and learning function. These results extend evidence from in
      vitro studies of synaptic and cell function and evidence from animals indicating
      the GCs can regulate substrates of memory function. While considerable evidence
      details these effects in adult humans and animals, relatively less is know about
      the effect of GCs on cognitive function in children and older adults.
      Investigators have suggested that children, particularly preschool-aged children,
      may be vulnerable to adverse consequences of increased GC secretion resulting
      from stress and neuropsychiatric diseases such as depression. Adverse GC effects
      on memory substrates and memory function in the adult have also fostered concern
      that age-related changes, including changes in GC receptors and changes in
      circulating cortisol levels, could lead to age-related increases in the adverse
      effect of GCs on brain function. Investigators have reported an association
      between age-related increases in cortisol levels and age-related memory decline,
      but this association may or may not be due to a direct effect of cortisol on
      memory substrates. A number of possible treatment approaches to prevent or
      remediate adverse GC-induced effects are under development. In general, the use
      of safe and effective agents for blocking adverse GC effects on brain functions
      including memory may offer benefits to individuals suffering acute and chronic
      stressors and could prevent brain changes relevant to stress, aging, and stress
      related neuropsychiatric diseases.

PMID- 11523846
TI  - Low cortisol and a flattening of expected daytime rhythm: potential indices of
      risk in human development.
AB  - Since the work of Hans Selye, stress has been associated with increased activity
      of the limbic-hypothalamic-pituitary-adrenocortical (LHPA) axis. Recently, a
      number of studies in adults have shown that this neuroendocrine axis may be
      hyporesponsive in a number of stress-related states. Termed hypocortisolism, the
      paradoxical suppression of the LHPA axis under conditions of trauma and prolonged
      stress presently challenges basic concepts in stress research. Adverse conditions
      that produce elevated cortisol levels early in life are hypothesized to
      contribute to the development of hypocortisolism in adulthood. However, as
      reviewed in this paper, hypocortisolism also may be a common phenomenon early in
      human childhood. Although preliminary at this point, the ubiquity of these
      findings is striking. We argue that developmental studies are needed that help
      explicate the origins of low cortisol and to determine whether the development of
      hypocortisolism is, in fact, preceded by periods of frequent or chronic
      activation of the LHPA axis. We also argue that developmental researchers who
      incorporate measures of salivary cortisol into their studies of at-risk
      populations need to be aware of the hypocortisolism phenomenon. Lower than
      expected cortisol values should not necessarily be relegated to the file drawer
      because they contradict the central dogma that stress must be associated with
      elevations in cortisol. Lastly, we note that evidence of low cortisol under
      adverse early life conditions in humans adds to the importance of understanding
      the implications of hypocortisolism for health and development.

PMID- 11523847
TI  - Developmental traumatology: the psychobiological development of maltreated
      children and its implications for research, treatment, and policy.
AB  - In this review, a developmental traumatology model of child maltreatment and the
      risk for the intergenerational cycle of abuse and neglect using a mental health
      or posttraumatic stress model was described. Published data were reviewed that
      support the hypothesis that the psychobiological sequelae of child maltreatment
      may be regarded as an environmentally induced complex developmental disorder.
      Data to support this view, including the descriptions of both psychobiological
      and brain maturation studies in maltreatment research, emphasizing the
      similarities and differences between children, adolescents, and adults, were
      reviewed. Many suggestions for important future psychobiological and brain
      maturation research investigations as well as public policy ideas were offered.

PMID- 11523848
TI  - Major depression and the stress system: a life span perspective.
AB  - From a transactional developmental perspective, the authors review findings from
      studies of animals and humans regarding a proposed relation between stress system
      abnormalities and major depression. The stress system has evolved to promote
      successful adaptation across the life span, but disruptions in its functioning
      may increase the risk of pathological outcomes. Emphasis is placed on the role of
      prenatal and early postnatal experience in contributing to individual differences
      in postnatal stress reactivity, which may interact with cognitive and
      psychosocial vulnerabilities to increase susceptibility to later onset of
      depression. Findings regarding cognitive, psychosocial, and medical sequelae of
      depression are also reviewed, with a focus on the possible mediating role of the
      stress system. The authors highlight the importance of multidisciplinary,
      longitudinal studies in attempting to gain a deeper understanding of the complex
      developmental processes involved in the onset and course of depression.

PMID- 11523849
TI  - Developmental vulnerabilities to the onset and course of bipolar disorder.
AB  - Different types of psychosocial stressors have long been recognized as potential
      precipitants of both unipolar and bipolar affective episodes and the causative
      agents in posttraumatic stress disorder (PTSD). New preclinical data have
      revealed some of the neurobiological mechanisms that could convey the long-term
      behavioral and biochemical consequences of early stressors. Depending on the
      timing, quality, quantity, and degree of repetition, maternal deprivation stress
      in the neonatal rodent can be associated with lifelong anxiety-like behaviors,
      increases in stress hormones and peptides. and proneness to drug and alcohol
      administration, in association with acute changes in the rate of neurogenesis and
      apoptosis (preprogrammed cell death) and decrements in neurotrophic factors and
      signal transduction enzymes necessary for learning and memory. Patients with
      bipolar illness who have a history of early extreme adversity (physical or sexual
      abuse in childhood or adolescence), compared with those without, show an earlier
      onset of illness, faster cycling frequencies, increased suicidality, more Axis I
      and Axis II comorbidities (including alcohol and substance abuse), and more time
      ill in more than 2 years of prospective follow-up. These findings are subject to
      a variety of interpretations, but to the extent that the more severe course of
      bipolar illness characteristics are directly and causally related to these early
      stressful experiences, early recognition and treatment of high-risk children
      could be crucial in helping to prevent or ameliorate the long-term adverse
      consequences of these stressors.

PMID- 11523850
TI  - Developmental effects of early immune stress on aggressive, socially reactive,
      and inhibited behaviors.
AB  - The origins of individual differences in social development are examined in
      relation to early stress (immune challenge) and social milieu (maternal behavior)
      in a genetic-developmental analysis using an animal model. Neonatal male mice (5
      or 6 days of age) from two lines of mice selectively bred for high versus low
      levels of inter-male aggressive behavior received a standard immune challenge
      (i.p. injections of 0.05 mg/kg endotoxin or saline). Animals were reared by their
      line-specific biological dam or by a foster dam from a line bred without
      selection. Adult levels of social behaviors were assessed in a dyadic test (age
      45-50 days). Mice from the high-aggressive line show more developmental
      sensitivity to immune challenge than mice from the low-aggressive line, and line
      differences persist regardless of the early maternal environment. As adults,
      endotoxin-treated mice from the high-aggressive line have lower levels of
      aggressive behavior, longer latency to attack, and higher rates of socially
      reactive and inhibited behaviors compared to saline controls. Developmental
      effects of endotoxin in the low-aggressive line are minimal: endotoxin increases
      socially reactive behaviors, compared to saline controls, but only for mice
      reared by their biological dams. Rearing by foster dams increases social
      exploration in the low-aggressive line. The findings raise novel questions
      regarding the openness of behavioral systems to effects of nonobvious but
      omnipresent features of the environment, such as antigenic load, how these
      effects are integrated to affect social development and psychopathology, and the
      nature of intrinsic factors that contribute to individual differences in
      sensitivity to early stressors.

PMID- 11523851
TI  - Salivary cortisol levels in children adopted from romanian orphanages.
AB  - Six and a half years after adoption. 6- to 12-year-old children reared in
      Romanian orphanages for more than 8 months in their first years of life (RO. n =
      18) had higher cortisol levels over the daytime hours than did early adopted (EA,
      < or = 4 months of age, n = 15) and Canadian born (CB, n = 27) children. The
      effect was marked, with 22% of the RO children exhibiting cortisol levels
      averaged over the day that exceeded the mean plus 2 SD of the EA and CB levels.
      Furthermore, the longer beyond 8 months that the RO children remained
      institutionalized the higher their cortisol levels. Cortisol levels for EA
      children did not differ in any respect from those of CB comparison children. This
      latter finding reduces but does not eliminate concerns that the results could be
      due to prenatal effects or birth family characteristics associated with orphanage
      placement. Neither age at cortisol sampling nor low IQ measured earlier appeared
      to explain the findings. Because the conditions in Romanian orphanages at the
      time these children were adopted were characterized by multiple risk factors,
      including gross privation of basic needs and exposure to infectious agents, the
      factor(s) that produced the increase in cortisol production cannot be determined.
      Nor could we determine whether these results reflected effects on the limbic
      hypothalamic-pituitary-adrenal axis directly or were mediated by differences in
      parent-child interactions or family stress occasion by behavioral problems
      associated with prolonged orphanage care in this sample.

PMID- 11523852
TI  - Maternal prenatal, postpartum, and concurrent stressors and temperament in 3-year
      olds: a person and variable analysis.
AB  - The study was based on the assumption that stressors in the lives of pregnant and
      parenting women are processes that affect prenatal, postpartum, and concurrent
      maternal hormones and emotions and that these processes affect child temperament.
      The hypotheses were tested in a group of 67 young mothers and their 3-year-old
      children. Mothers were clustered into groups based on longitudinal patterns of
      hormones and emotions at prenatal, postpartum. and 3-year follow-up assessments.
      The analyses focused on relating maternal patterns of hormones and emotions to
      the child's temperament at age 3 years. Temperament was assessed by questionnaire
      and observation of behavior during a challenging situation. Illustrative findings
      included the following. Verbal aggression and nonverbal aggression were
      significantly higher in children of mothers in the low prenatal hormone cluster
      than children of mothers in the high prenatal hormone cluster. Children of
      mothers in the postpartum low testosterone (T), estradiol (E2), and
      androstenedione (delta4-A) and medium cortisol (Cort) cluster (mainly low hormone
      cluster) exhibited significantly more physical aggression than children of
      mothers in the medium T and A4-A, high E2 and low Cort cluster. Maternal patterns
      of hormones, emotions, and parenting attitudes and practices were related to
      multiple aspects of temperament when the children were age 3 years. The findings
      support the important role of maternal biological and psychological processes in
      the development of child temperament.

PMID- 11523853
TI  - Can poverty get under your skin? basal cortisol levels and cognitive function in
      children from low and high socioeconomic status.
AB  - It is well known that individuals from more advantaged social classes enjoy
      better mental and physical health than do individuals within lower classes.
      Various mechanisms have been evoked to explain the association between
      socioeconomic status (SES) and health. One mechanism that has received particular
      attention in recent years is stress. It has been shown that individuals lower in
      SES report greater exposure to stressful life events and a greater impact of
      these events on their life than individuals higher in SES. In order to measure
      whether the development of the relationship between SES and mental health is
      sustained by exposure to high levels of glucocorticoids, we measured morning
      salivary cortisol levels as well as cognitive function (memory, attention, and
      language) in 307 children (from 6 to 16 years of age) from low versus high SES in
      the Montreal area in Canada. The results revealed that low SES children from 6 to
      10 years old present significantly higher salivary cortisol levels when compared
      to children from high SES. This difference disappears at the time of school
      transition, and no SES differences are observed in salivary cortisol levels
      during high school. However, children from low and high SES do not differ with
      regard to memory or to attentional and linguistic functions. Also, mothers of low
      SES children reported higher feelings of depression and more unhealthy behaviors,
      while mothers of high SES children reported higher stress related to work or
      family transitions. Altogether, these results show that low SES in young children
      is related to increased cortisol secretion, although the impact of SES on
      cortisol secretion is absent after transition to high school. These data are
      interpreted within the context of the equalization process of class patterning.
      Four social explanatory factors are suggested to explain the disappearance of SES
      differences in basal cortisol levels after school transition, taking into account
      the influence of family environment on the child's secretion of stress hormones.

PMID- 11523854
TI  - Diverse patterns of neuroendocrine activity in maltreated children.
AB  - Cortisol regulation was investigated in a sample of school-aged maltreated (n =
      175) and demographically comparable low-income nonmaltreated (n = 209) children
      in the context of a day camp research program. Overall group differences between
      maltreated and nonmaltreated children were not found for average morning or
      average afternoon cortisol levels. However, significant variations were found
      that were based on the subtypes of maltreatment that the children had
      experienced. Maltreated children who had been both physically and sexually abused
      (as well as neglected or emotionally maltreated) exhibited substantial elevations
      in morning cortisol levels; children who had high (>1 SD) cortisol levels in both
      the morning and afternoon were also overrepresented in the multiple abuse group.
      Developmental timing of maltreatment did not account for these group differences,
      whereas the severity of sexual abuse was implicated. In contrast to the multiple
      abuse group, a subgroup of physically abused children showed evidence of a trend
      toward lower morning cortisol relative to nonmaltreated children with a
      significantly smaller decrease in cortisol levels from morning to afternoon. The
      findings are discussed in terms of the diversity of atypical cortisol regulation
      patterns that are exhibited among maltreated children.

PMID- 11523855
TI  - Adrenocortical activity in at-risk and normally developing adolescents:
      individual differences in salivary cortisol basal levels, diurnal variation, and
      responses to social challenges.
AB  - The purpose of this study was to examine adrenocortical activity (basal, diurnal
      variation, and responses to social stressors) in adolescents at risk for
      psychopathology. Salivary cortisol levels were examined in normally developing
      and at-risk youth with internalizing and externalizing symptoms ranging from
      subclinical to clinical levels. Adolescents showed expected patterns of diurnal
      variation, with high early morning cortisol levels and a pattern of decline
      throughout the day. Females showed higher midday and late afternoon levels than
      males, and these patterns interacted with risk status. Internalizing problems
      sometimes were associated with gradual rather than steep declines in basal
      cortisol production. Both immediate and delayed cortisol reactivity to a social
      performance stressor were associated with internalizing symptoms. There was no
      evidence of relations between externalizing problems and underarousal of the
      hypothalamic-pituitary-adrenal (HPA) system. These and other results suggest that
      gender is an important moderating factor linking psychopathology. development,
      and context with HPA axis functioning in adolescence.

PMID- 11523856
TI  - Developmental changes in cortisol secretion in normal and at-risk youth.
AB  - Adolescence is associated with an increase in the rate of certain psychiatric
      symptoms, and it is typically the developmental period when prodromal features of
      the major psychiatric disorders emerge. This is especially true of schizophrenia,
      with the majority of patients showing a marked postpubertal rise in schizotypal
      signs that predates the onset of clinical symptoms in early adulthood. Cross
      sectional studies of youth have revealed a positive correlation between age and
      saliva cortisol level, suggesting a normative maturational increase in activity
      of the hypothalamic-pituitary-adrenal (HPA) axis. It has been hypothesized that
      this increase may trigger the expression of symptoms in vulnerable individuals.
      The present longitudinal study measured cortisol secretion and its relation with
      symptom development in samples of youth with schizotypal personality disorder
      (SPD), other personality disorders, or no Axis II disorder. The findings indicate
      moderate stability in cortisol levels across a 2-year period, with a longitudinal
      increase in cortisol levels over time. Cortisol levels at the first and second
      assessments were correlated with the severity of SPD symptoms at follow-up. The
      results are consistent with the notion that the HPA axis undergoes a postpubertal
      maturational process that moderates the expression of psychiatric symptoms.

PMID- 11523857
TI  - Childhood trauma and risk for PTSD: relationship to intergenerational effects of
      trauma, parental PTSD, and cortisol excretion.
AB  - Among the adverse mental health consequences of childhood trauma is the risk
      related to the development of posttraumatic stress disorder (PTSD) in adulthood.
      Other risk factors for PTSD. including parental trauma exposure and parental
      PTSD, can also contribute to the experience of child trauma. We examined
      associations between childhood trauma and PTSD in 51 adult children of Holocaust
      survivors and 41 comparison subjects. in consideration of parental trauma
      exposure and parental PTSD. We also examined these variables in relation to 24-hr
      urinary cortisol levels. Adult offspring of Holocaust survivors showed
      significantly higher levels of self-reported childhood trauma, particularly
      emotional abuse and neglect. relative to comparison subjects. The difference was
      largely attributable to parental PTSD. Self-reported childhood trauma was also
      related to severity of PTSD in subjects, and emotional abuse was significantly
      associated with 24-hr mean urinary cortisol secretion. We conclude that the
      experience of childhood trauma may be an important factor in the transmission of
      PTSD from parent to child.

PMID- 11523858
TI  - Propriety, scientific integrity, and publication.

PMID- 11523859
TI  - Characterization of light penetration in rat tissues.
AB  - OBJECTIVE: The goal of this study is to determine the optical properties of
      different rat tissues with respect to spatial intensity variation and light
      distribution. We are interested mainly in the wavelength of 630 nm. Nevertheless,
      for liver tissue we have used 514 nm and 670 nm as well. BACKGROUND DATA: In the
      past, many articles have been written about the interaction of lasers with rat
      tissues. However, the technique of imaging the light distribution allows us to
      obtain the spatial scattering as well as an effective attenuation coefficient for
      the light intensity. METHODS: Slices of different rat tissues were placed between
      two microscope slide mounts (spaced by 3 mm). A laser beam was irradiated on the
      sandwiched tissue. A CCD camera placed on the side, orthogonal to the beam path,
      recorded the intensity distribution of the scattered light. Analysis of this
      spatial intensity profile allowed determining the variation of the intensity as
      the light penetrates the tissue. RESULTS: We have found that abdominal wall fat
      presents the lowest exponential decay when compared with liver, muscle, and
      kidney. The obtained values provided good data about the light distribution in
      those tissues when irradiated with a nondiffuse laser beam. For all tissues, we
      observed a spherical light distribution and exponential decay. Cirrhotic liver
      shows much stronger decay than healthy liver. These results are useful for
      several applications of laser for biostimulation a phototherapy.

PMID- 11523860
TI  - Conservative closure of antro-oral communication stimulated with laser light.
AB  - OBJECTIVE: To evaluate application of laser biostimulation in the treatment of
      antro-oral communications. BACKGROUND DATA: Sixty-one patients between the ages
      of 14 and 58 were subjected to biostimulation with laser light. Therapy was
      performed with a CTL 1106 biostimulative laser of 30 mW power with a tip-emitting
      light of 830-nm wavelength. METHODS: Three cycles of laser irradiation were
      performed in a continuous mode. During one cycle, 3.5 min of extraoral
      irradiation of 4J with the contact "sweeping" method or the "woodpecker
      technique" was made through the facial skin to the suborbital region, 3.5 min of
      intraoral irradiation of 4J with the contact "point" method to the region of
      maxillary sinus floor, and 3.5 min of intraoral one of 4J with the contact
      "point" method to the alveolar process at the site of the antro-oral
      communication. The above cycle of irradiation was repeated for 4 days. RESULTS:
      After 4 days of laser therapy, a complete closure of antro-oral communication
      occurred. CONCLUSION: Laser therapy can be recommended as an effective method of
      treatment in this type of complication following tooth extraction.

PMID- 11523861
TI  - Office-based CO2 laser-assisted tympanic membrane fenestration addressing otitis
      media with effusion.
AB  - OBJECTIVE: To use the CO2 laser-assisted tympanic membrane fenestration in office
      settings, under local anesthesia, as the sole treatment for patients with chronic
      otitis media with effusion (OME). BACKGROUND DATA: This new treatment ensures
      artificial ventilation of the middle ear for several weeks, and provides an
      intermediate solution between ordinary lancet-made tympanocentesis and
      transtympanic ventilation tube insertion. The operative technique is already well
      codified, and preliminary studies have demonstrated that tympanic membrane
      fenestration does not expose patients to any major hazard. METHODS: We treated 30
      ears in 21 children and 29 ears in 24 adults. All patients had presented with OME
      persistent for more than 3 months. The laser tympanostomy was performed under
      local anesthesia, as an outpatient procedure, using a CO2 flash-scanning laser in
      conjunction with a handpiece (OTOLAM). Using a power of 12 W to 17 W, a single
      laser pulse usually sufficed to create a 2-mm-diameter circular perforation in
      the anteroinferior quadrant of the eardrum. RESULTS: The tympanic membrane
      fenestration allows avoiding ventilation tube insertion in 63% of children and
      75% of adults. CONCLUSIONS: The CO2 laser-assisted tympanic membrane fenestration
      seems a valid therapeutic option addressing OME. This study should be pursued on
      a larger scale to define more precisely the indications of the laser
      tympanostomy.

PMID- 11523862
TI  - Treatment of lymphangioma with Nd:YAG laser irradiation: a case report.
AB  - OBJECTIVE: In this case report, the treatment of a buccal lymphangioma in a 9
      year-old female was done using the Nd:YAG laser and the clinical outcome was
      evaluated. BACKGROUND DATA: The treatment of lymphangioma with the laser surgery
      using Nd:YAG and CO2 laser has become favorable due of a lack of postoperative
      pain and hemorrhage. METHODS: The lesion was treated with a pulsed Nd:YAG laser
      (d-lase 300, American Dental Laser, Detroit, MI). An exposure of 10 min each was
      performed at an interval of 10 days by the noncontact method with the energy
      density of 1 W, 10 Hz. RESULTS: It was observed that there was a great reduction
      of the lesion and a considerable reduction of the external facial volume. As the
      excision of the lesion was avoided in our present study, there was no pain and
      hemorrhage. A remarkable reduction of the tumor size could be observed visually
      within the five laser exposures. CONCLUSIONS: It can be concluded that if Nd:YAG
      laser therapy is used for reducing the tumor size as a primary treatment, the
      operation becomes easy and the recurrence may be less than with the conventional
      treatment, and an option of a surgical or laser excision could be reserved.

PMID- 11523863
TI  - The use of Er:YAG, Nd:YAG and Ga-Al-As lasers in periapical surgery: a 3-year
      clinical study.
AB  - OBJECTIVES: In an attempt to increase the successful rate of endodontic surgical
      procedures this study proposes the use of an association of three lasers in
      apicectomy: Er:YAG laser, (wavelength 2.94 microm pulse mode), Nd:YAG laser
      (wavelength 1.064 microm, pulse mode), and Ga-Al-As laser, (wavelength of 790 nm,
      continuous wave). BACKGROUND DATA: Previous studies have shown the low success
      rate of apicectomy by conventional methods due to the presence of remaining
      bacteria in the surgical site. METHODS: The Er:YAG laser was used to perform
      osteotomy and root resection without vibration, discomfort, less contamination of
      the surgical site, and no smear-layer on the dentine surface. The Nd:YAG laser
      irradiation through a fiber performed sealing of the dentinal tubules and
      bacterial reduction of the cavity bone. In addition, the improvement of healing
      and better post-operative achieved with the Ga-Al-As laser encourages the use of
      those lasers in periapical surgeries. RESULTS: Three years follow-up examination
      of the clinical case showed radiographically significant decrease of the
      radiolucent periapical area and no clinical signs and symptoms. CONCLUSION: The
      outcome of this clinical case indicates that the use of those lasers could be
      considered an alternative, suitable, and useful method to perform an apicectomy.

PMID- 11523865
TI  - Laser literature watch.

PMID- 11523864
TI  - Comparative study of influence on tensile bond strength of a composite to dentin
      using Er:YAG laser, air abrasion, or air turbine for preparation of cavities.
AB  - OBJECTIVES: The purpose of this study was to evaluate, in vitro, the tensile bond
      strength of the Single Bond (3M) adhesive system placed over dentin surfaces
      treated with air turbine, Er:YAG laser without contact and in focused or air
      abrasion. SUMMARY BACKGROUND DATA: The use of dentin adhesives is a well
      established clinical routine among the dentists. However, there have been few
      reports comparing the influence of the Er:YAG laser, air abrasion, and air
      turbine on the Single Bond tensile bond strength of adhesives systems to dentin
      fact that could influence which tools dentists select for use in cavity
      preparations. METHODS: Twenty-three extracted retained human molars were used in
      this study. The coronal portion was divided in two parts and fixed in acrylic
      resin; the occlusal surface was abraded to a 2-mm width with a mechanic lathe
      until the dentin surface was completely exposed. The dental portions were divided
      into three groups of 15 each and treated with Er:YAG laser, air abrasion, or air
      turbine. A 3 mm hole in the center of each tooth was marked off using contact
      paper. Single Bond (3M) adhesive system was applied after acid phosphoric at 35%
      application for 15 sec over dentin surfaces. A resin composite cone was built
      into the delimited area to accomplish the tensile bond strength test on the EMIC
      universal test machine. The specimens were then evaluated by stereoscopy to
      determine the type of failures into the dentin-adhesive-resin composite surface.
      RESULTS: The tensile test was performed using the universal testing machine EMIC
      DL-2000 at a cross-head speed of 0.5 mm/min. The average results were: air
      turbine (17.52 MPa), Er:YAG laser (16.65 MPa) and air abrasion (15.83 MPa).
      Statistical treatment by ANOVA and Tukey's test (p < 0.01) showed no significant
      differences between the groups tested. The tensile bond strength test to the
      dentin showed no significant difference among the three groups when the Single
      Bond was used after the 35% phosphoric-acid conditioning. The stereoscopy showed
      a predominant adhesive failure in all groups. CONCLUSION: These results suggest
      that Single Bond tensile bond strength is the same as dentin prepared by Er:YAG
      laser, air abrasion, or air turbine.

PMID- 11523866
TI  - The predictive impact of domestic violence on three types of child maltreatment.
AB  - OBJECTIVE: This exploratory study investigated the co-occurrence of domestic
      violence and three types of child maltreatment: physical child abuse,
      psychological child abuse, and child neglect. METHOD: A sample of 2544 at-risk
      mothers with first-born children participated in a home-visiting child abuse
      prevention program. A longitudinal design using multiple data collection methods
      investigated the effect of domestic violence during the first 6 months of child
      rearing on confirmed physical child abuse, psychological child abuse, and child
      neglect up to the child's first 5 years. RESULTS: Logistic regressions revealed
      significant relationships between domestic violence and physical child abuse,
      psychological child abuse, and child neglect. These effects were significant
      beyond the significant effects of known risks of maltreatment, as measured by the
      Kempe Family Stress Inventory (KFSI). Domestic violence occurred in 59 (38%) of
      the 155 cases of confirmed maltreatment. Domestic violence preceded child
      maltreatment in 46 (78%) of the 59 cases of co-occurrence, as indicated by
      independent home observations and child protective service records. CONCLUSIONS:
      The findings indicate that domestic violence during the first 6 months of child
      rearing is significantly related to all three types of child maltreatment up to
      the child's fifth year. Domestic violence and risks factors measured on the KFSI
      continue to contribute to all three types of maltreatment up to the child's fifth
      year. Prevention programs would be wise to provide services to at-risk families
      until the child is at least 5 years old. Addressing concurrent problems during
      treatment may enhance intervention.

PMID- 11523867
TI  - The incidence of witnessing interparental violence and some of its psychological
      consequences among Arab adolescents.
AB  - OBJECTIVES: The study had two aims. First, it sought to examine the incidence of
      interparental psychological aggression and physical violence witnessed by Arab
      adolescents. Second, it sought to assess the implications of such exposure on
      adolescents' feelings of hopelessness, psychological adjustment problems, and
      self-esteem. METHOD: A cross-sectional survey was conducted among a sample of
      1640 Arab adolescents from Israel. Different forms of the Conflict Tactics Scales
      (CTS) were utilized to measure the extent of interparental psychological
      aggression and physical violence witnessed by adolescents. The Hopelessness Scale
      for Children (HSC), the Psychological Adjustment Scale (PAS), and the Rosenberg
      Self-Esteem Scale (RSE) were used to measure the above-mentioned psychological
      states. RESULTS: The results indicate that Arab adolescents witness high rates of
      psychological aggression and physical violence between their parents.
      Furthermore, regression and multiple regression analyses revealed that
      significant amounts of the variance in adolescents' hopelessness, psychological
      adjustment problems, and low self-esteem are explained by witnessing different
      patterns of interparental psychological aggression and physical violence, beyond
      the amounts of variance in these criterion variables that can be attributed to
      some sociodemographic characteristics of the adolescents, their parents, and
      families. CONCLUSIONS: The results provided strong support for the hypothesis
      that witnessing interparental aggression and violence has a strong detrimental
      impact on adolescents' psychological states. Furthermore, the results emphasize
      the need for further research into the effects of witnessing other patterns of
      psychological aggression and physical violence in adolescents' nuclear and
      extended families. It would also be worthwhile to investigate the risk factors
      that predispose violence in the family and the consequences of those factors.

PMID- 11523868
TI  - Childhood sexual abuse, parenting and postpartum depression--a 3-year follow-up
      study.
AB  - OBJECTIVE: This study is the second and final phase of a 3-year follow-up study
      of women who had been admitted with a major depressive episode in the postpartum
      period, along with their children and partners where present. The effect of a
      maternal sexual abuse history on the women's well-being and child outcome
      compared to those women without such a history is highlighted. METHOD: Forty-five
      of an original cohort of 56 women were seen with their child where possible, when
      the child was an average of 36.8 months old. Twenty-two women had no history of
      sexual abuse, and 23 gave a history of childhood sexual abuse. Women were
      assessed with respect to well-being, relationships, parenting stress and
      psychiatric history since recruitment. The child's behavior and cognitive
      development was also assessed. RESULTS: Women with a history of sexual abuse
      rated higher depression and anxiety scores (p < .05), and had greater life
      stresses (p < .05). Their partners rated themselves as more comforting and their
      children as more disturbed (p < .05). Over time, this group had failed to improve
      as much as the nonabuse group on these measures. There was no difference in child
      cognitive scores between groups. CONCLUSIONS: A history of sexual abuse in women
      who become depressed postpartum may have long term implications for the woman's
      mental health, her relationship with her child, as well as the emotional
      development of her child. It is critical to offer women in this high-risk group
      supports in an attempt to minimize these difficulties and any long-term adverse
      effects.

PMID- 11523869
TI  - Psychiatric co-morbidity in caregivers and children involved in maltreatment: a
      pilot research study with policy implications.
AB  - OBJECTIVE: The purpose of this study was to determine the lifetime incidence of
      mental disorders in caregivers involved in maltreatment and in their maltreated
      child. METHODS: Lifetime DSM-III-R and IV psychiatric diagnoses were obtained for
      53 maltreating families, including at least one primary caregiver and one proband
      maltreated child or adolescent subject (28 males, 25 females), and for a
      comparison group of 46 sociodemographically, similar nonmaltreating families,
      including one proband healthy child and adolescent subject (22 males, 22
      females). RESULTS: Mothers of maltreated children exhibited a significantly
      greater lifetime incidence of anxiety disorders (especially post-traumatic stress
      disorder), mood disorders, alcohol and/or substance abuse or dependence disorder,
      suicide attempts, and comorbidity of two or more psychiatric disorders, compared
      to control mothers. Natural fathers or mothers' live-in mates involved in
      maltreatment exhibited a significantly greater lifetime incidence of an alcohol
      and/or substance abuse or dependence disorder compared to controls. The majority
      of maltreated children and adolescents reported anxiety disorders, especially
      post-traumatic stress disorder (from witnessing domestic violence and/or sexual
      abuse), mood disorders, suicidal ideation and attempts, and disruptive disorders.
      Most maltreated children (72%) suffered from comorbidity involving both emotional
      and behavioral regulation disorders. CONCLUSIONS: Families involved in
      maltreatment manifest significant histories of psychiatric comorbidity. Policies
      which target identification and treatment of comorbidity may contribute to
      breaking the intergenerational transmission of maltreatment.

PMID- 11523870
TI  - The factors of child physical abuse in Korean immigrant families.
AB  - OBJECTIVE: This study explores Korean immigrant mothers' attitudes toward child
      physical abuse based on an ecological perspective. METHOD: One hundred and forty
      four Korean immigrant mothers who came to the US after age 16 and have at least
      one child under 18 years old participated in this study. Data were collected
      using instruments translated in Korean that measure mothers' attitudes toward
      child physical abuse in four areas: degree of agreement with physical abuse,
      conflict tactics, belief in the use of physical punishment, and perceptions
      regarding physical abuse. RESULTS: This study found that the following variables
      affect Korean immigrant mothers' attitudes toward child physical abuse at
      ecological levels of the environment: amount of time spent with children,
      experience of corporal punishment as a child, children's gender and age, family
      acculturation conflicts, mothers' age, and length of time in US at the micro
      level; involvement in their children's school and involvement in social
      organizations at the meso level; level of education and reported stress of
      immigrant life at the exo level; value of children in Korean culture, familiarity
      with Child Protective Services (CPS), perceived discrimination, and value of
      corporal punishment at the macro level. CONCLUSIONS: This study suggests the
      importance of cultural sensitivity in social work practice when working with
      Korean immigrants. It also implies that intervention and prevention efforts of
      child abuse should be targeted at more than one level of the environment.

PMID- 11523871
TI  - Child sexual abuse and incest: community-based intervention.
AB  - OBJECTIVE: The primary aim of this article is to determine the effectiveness of
      community intervention in the case of child sexual abuse. The article describes
      and analyses an actual case in a small urban community in Israel. METHOD: After
      several incidents of child sexual abuse, much of it incestuous, were brought to
      light in the community, they were discussed openly, contained, and punished. A
      community campaign, in which community activists as well as all the service
      providers were involved, was organized by community social workers. Individual,
      group, and community interventions were used. RESULTS: The continuation of the
      abuse has been checked, and, so far, there is no evidence to suggest its
      resurgence. Community apathy to child sexual abuse seems to have been halted and
      reversed. The involvement of community residents, particularly the activists, has
      increased, and this appears to be the major factor in changed community norms
      toward child sexual abuse. CONCLUSION: Implications of the individual, group, and
      community interventions are discussed. An integrated program of intervention
      practices is advocated to contain and prevent the incidence of child sexual abuse
      and incest.

PMID- 11523872
TI  - Psychological functioning and family discord among African-American adolescent
      females with and without a history of childhood sexual abuse.
AB  - OBJECTIVES: The aim was to examine the rate of childhood sexual abuse along with
      the factors (age of abuse onset, type of perpetrator, and duration of the abuse),
      as well as the relationship of these factors to psychological functioning among
      females with a history of childhood abuse. Second, to determine whether levels of
      psychological functioning and family discord differ among females with and
      without a history of childhood sexual abuse. METHOD: A cross-sectional design was
      used. Two hundred and forty-nine adolescent females were recruited from a
      community-based health program. Two trained female interviewers administered an
      anonymous survey that assessed childhood sexual abuse, psychological functioning,
      and family environment. RESULTS: Fifty-seven (22.9%) of those surveyed reported
      childhood sexual abuse, of which 44.3% were intrafamilial and 55.7% were
      interfamilial. Age at onset ranged from 3 years to 17 years; 62.5% reported that
      the sexual abuse occurred 1 to 4 times; 27.9% reported a duration ranging from 1
      year to 13 years; and 9.6% reported a duration of 1 month to 7 months. Multiple
      regression analysis revealed that a greater duration predicted higher levels of
      depression and lower levels of self-esteem among females with a history of sexual
      abuse. Females with a history of childhood sexual abuse scored significantly
      lower on measures of self-esteem and mastery, and significantly higher on
      measures of physical and emotional abuse. CONCLUSIONS: Results indicate that
      adolescent females with a history of childhood sexual abuse suffer an array of
      negative sequelae that include psychological and family distress.

PMID- 11523873
TI  - A comparison of physical and sexual abuse: histories of sexual and non-sexual
      offenders with intellectual disability.
AB  - OBJECTIVES: To review patterns of physical and sexual abuse in cohorts of sexual
      offenders and nonsexual offenders with intellectual disability. METHOD: Forty-six
      sexual offenders were compared with 48 male nonsexual offenders in relation to
      their experiences of sexual and physical abuse in childhood. Comprehensive
      assessments were taken over a period of at least one year, and were conducted
      independently by a range of professionals. RESULTS: Thirty-eight percent of the
      sexual offenders and 12.7% of the nonsexual offenders had experienced sexual
      abuse, while 13% of the sexual offenders and 33% of the nonsexual offenders had
      experienced physical abuse. CONCLUSIONS: Sexual abuse seems a significant
      variable in the history of sexual offenders, while physical abuse seems a
      significant variable in the history of nonsexual offenders. The results support
      the view that the "cycle of abuse" is neither inevitable nor an adequate
      explanation of future offending.

PMID- 11523874
TI  - No wash-over.

PMID- 11523875
TI  - Scope of the OSCE.

PMID- 11523876
TI  - Internet access to dental register.

PMID- 11523878
TI  - Prescribing limitations.

PMID- 11523877
TI  - Prescribing limitations.

PMID- 11523880
TI  - Clinical protocols.

PMID- 11523879
TI  - Lead exposure.

PMID- 11523881
TI  - Competency in sedation.
AB  - Conscious sedation has become an integral part of the undergraduate dental
      curriculum. The attributes of the competent graduate in sedation are defined and
      all providers of sedation education should be aiming towards this standard. It is
      important that students receive appropriate theoretical and practical training
      which must include hands-on clinical experience in sedation techniques.

PMID- 11523882
TI  - Integrating posterior crowns with partial dentures.
AB  - This article outlines those considerations which are important in integrating
      posterior crowns with partial dentures. Planning the support and retention of the
      denture prior to crown construction will enhance patient treatment. Modification
      of the crown preparation to incorporate rest seats, retentive areas, guide planes
      and a planned path of insertion may be necessary.

PMID- 11523883
TI  - Learning styles.
AB  - Before we can draw up our plan we need to first look at learning itself, and be
      aware that a number of different learning styles exist which can influence our
      choice of appropriate training.

PMID- 11523884
TI  - Oral submucous fibrosis in a 11-year-old Bangladeshi girl living in the United
      Kingdom.
AB  - A case of oral submucous fibrosis occurring in a 11-year-old Bangladeshi girl is
      presented. This paper reviews the aetiology, clinical presentation and treatment
      modalities of oral submucous fibrosis. This case highlights the link between oral
      submucous fibrosis and the regular use of areca-nut (paan) and the newer
      transcultural oral tobacco products. This association has been reported among
      children resident in the Indian sub-continent but is unrecorded for United
      Kingdom residents. The case report underlines the danger that children face with
      products which are clearly targeted at them by the tobacco industry.

PMID- 11523885
TI  - Caries incidence following restoration of shortened lower dental arches in a
      randomized controlled trial.
AB  - CONTEXT: Removable partial dentures used to restore the shortened lower dental
      arch may adversely affect the remaining natural teeth and are associated with a
      low prevalence of use. OBJECTIVE: To report the findings for caries incidence 2
      years after restoration of lower shortened arches with bilateral cantilever resin
      bonded bridges (RBBs) and conventional partial dentures (RPDs). DESIGN:
      Randomised controlled trial. SETTING: Secondary care PATIENTS: 25 male and 35
      female subjects of median age 67 years. were randomly allocated to 'bridge' and
      'denture' treatment groups of 30 patients each matched for age and sex. Caries
      incidence was recorded during dental examinations 3 months, 1 and 2 years after
      insertion of new lower prostheses. INTERVENTIONS: Cantilever RBBs and
      conventional RPDs with cast metal frameworks. RESULTS: There was a highly
      significant difference in the frequency of new caries lesions, 11 and 51 in the
      bridge and denture groups respectively (P < 0.01). 20 out of 27 bridge patients
      and 9 of 23 denture patients had no caries experience. Multivariate modeling
      identified treatment group as the only significant predictor of caries
      occurrence. CONCLUSIONS: Two years after restoration of lower shortened arches
      for an elderly sample of patients, there was a significantly greater incidence of
      new and recurrent caries lesions in subjects restored with RPDs compared with
      cantilever RBBs.

PMID- 11523886
TI  - The use of fibre-optic transillumination in general dental practice.
AB  - OBJECTIVE: To assess the use of fibre-optic transillumination (FOTI) as a
      diagnostic tool in general dental practice. DESIGN: A cross-over quantitative
      study for the diagnosis of approximal carious lesions by two clinical methods
      with a qualitative component. SUBJECTS AND METHODS: Seven GDPs were trained to
      use FOTI as an adjunct to their usual clinical examination to diagnose approximal
      caries. After 12 weeks of use in their practices four of the GDPs took part in
      two assessment sessions, set a week apart, using 29 volunteer patients. Each
      patient was examined on two separate occasions by each GDP using either their
      standard clinical examination technique alone or supplemented by FOTI
      examination. The order of the techniques was randomised. Radiographs of each
      patient were also examined separately. An experienced FOTI user also examined the
      patients to provide a benchmark. From standard charts the number of enamel and
      dentinal lesions on approximal surfaces was summed and comparisons made between
      the techniques. Six GDPs took part in one-to-one interviews. MAIN OUTCOME
      MEASURES: Mean numbers ofcarious lesions recorded by each clinician using each
      technique. RESULTS: There was a trend for all GDPs to find more enamel and
      dentinal lesions using FOTI, than with their standard clinical examination with
      or without radiographs. All GDPs found the FOTI technique a useful adjunct. They
      used FOTI in different ways and found a variety of uses for it other than caries
      diagnosis. CONCLUSIONS: The

PMID- 11523887
TI  - The bonding of composite resin to moist enamel.
AB  - OBJECTIVE: To determine the effect on the bond strength of modern dentine bonding
      agents to etched enamel of surface contamination with water. DESIGN: Fifteen bond
      strength measurements were made for bonds prepared to both moist and dry etched
      enamel for each of three test and one control materials. RESULTS: For two
      materials (Scotchbond 1 and Prime and Bond 2.1) the bond strength was not
      affected by the presence of water on the etched enamel surface. A mean bond
      strength in excess of 25 MPa was achieved for both materials under all
      conditions. One material (Optibond Solo) showed a 30% increase in bond strength
      when bonds were formed under wet condition (21.10 MPa compared with 15.35 MPa).
      The bond strength of the control material, a conventional unfilled bonding resin,
      decreased markedly with aqueous contamination (9.14 MPa compared with 26.75 MPa).
      CONCLUSION: Etched enamel should be rehydrated routinely prior to bonding
      composite resin to its surface using a water displacing dentine bonding system.

PMID- 11523888
TI  - Planning oral rehabilitation: case-based computer assisted learning in clinical
      dentistry.
AB  - The partially edentulous adult offers a unique and problem-rich resource as a
      basis for a case-based learning scenario in clinical dentistry in the field of
      planning oral rehabilitation. However, there is little resource material
      available to help students negotiate the territory between diagnosis and
      treatment options of discrete conditions and treatment sequencing once decisions
      have been made. To address the educational void surrounding the teaching and
      learning of oral rehabilitation strategies, the authors have developed a CD-ROM
      'Interactive Learning in Dentistry: Decision making in the oral rehabilitation of
      the partially edentulous adult'. The disc emphasises the distinction between
      'doing' and 'planning to do' in the decision-making process. After using the disc
      the students should be able to apply a generic framework to formulate a custom
      oral rehabilitation plan for their own patient. The disc was evaluated by final
      year students from the Faculty of Dentistry, University of Sydney. Response to
      the program was essentially positive and comments from students have impacted on
      further development.

PMID- 11523889
TI  - Just a little something.

PMID- 11523891
TI  - Novel haloarchaeal 16S rRNA gene sequences from Alpine Permo-Triassic rock salt.
AB  - Prokaryotic diversity in Alpine salt sediments was investigated by polymerase
      chain reaction (PCR) amplification of 16S rRNA genes, sequencing of cloned
      products, and comparisons with culturable strains. DNA was extracted from the
      residue following filtration of dissolved Permo-Triassic rock salt. Fifty-four
      haloarchaeal sequences were obtained, which could be grouped into at least five
      distinct clusters. Similarity values of three clusters to known 16S rRNA genes
      were less than 90%-95%, suggesting the presence of uncultured novel taxa; two
      clusters were 98% and 99% similar to isolates from Permo-Triassic or Miocene salt
      from England and Poland, and to Halobacterium salinarum, respectively. Some rock
      salt samples, including drilling cores, yielded no amplifiable DNA and no cells
      or only a few culturable cells. This result suggested a variable distribution of
      haloarchaea within different strata, probably consistent with the known geologic
      heterogeneity of Alpine salt deposits. We recently reported identical culturable
      Halococcus salifodinae strains in Permo-Triassic salt sediments from England,
      Germany, and Austria; together with the data presented here, those results
      suggest one plausible scenario to be an ancient continuous hypersaline ocean
      (Zechstein sea) populated by haloarchaea, whose descendants are found today in
      the salt sediments. The novelty of the sequences also suggested avoidance of
      haloarchaeal contaminants during our isolation of strains, preparation of DNA,
      and PCR reactions.

PMID- 11523890
TI  - Identification and molecular characterization of an endoglucanase gene, celS,
      from the extremely thermophilic archaeon Sulfolobus solfataricus.
AB  - A genomic region upstream of the alcohol dehydrogenase (Ssadh) gene was cloned
      and sequenced from a library of Sulfolobus solfataricus MT4 strain. The isolated
      4,040-bp DNA fragment revealed an open reading frame (celS), lying in the
      opposite direction to Ssadh, which showed significant similarity to endo-beta-1,4
      glucanases from Pyrococcus furiosus, Thermotoga maritima, and Thermotoga
      neapolitana. celS was shown to be a functional gene in vivo: a specific celS mRNA
      was detected by primer extension analysis showing a unique initiation
      transcription site coinciding with the ATG translation initiation codon. The
      specific gene product was detected as an extracellular cellulase after enzyme
      staining by carboxymethyl cellulose (CMC) SDS-PAGE, showing a molecular weight in
      agreement with that deduced from the open reading frame. Depending on growth
      conditions, different levels of cellulase activity and specific celS transcript
      were detected, revealing an inductive effect of CMC and suggesting a repressive
      role of glucose.

PMID- 11523892
TI  - Cloning, expression, and structure analysis of carbamate kinase-like carbamoyl
      phosphate synthetase from Pyrococcus abyssi.
AB  - Pyrococcus abyssi, a hyperthermophilic archaeon found in the vicinity of deep-sea
      hydrothermal vents, grows optimally at temperatures around 100 degrees C.
      Carbamoyl phosphate synthetase (CPSase) from this organism was cloned and
      sequenced. The active 34-kDa recombinant protein was overexpressed in Escherichia
      coli when the host cells were cotransformed with a plasmid encoding tRNA
      synthetases for low-frequency Escherichia coli codons. Sequence homology suggests
      that the tertiary structure of P. abyssi CPSase, resembling its counterpart in
      Pyrococcus furiosus, is closely related to the catabolic carbamate kinases and is
      very different from the larger mesophilic CPSases. P. furiosus CPSase and
      carbamate kinase form carbamoyl phosphate by phosphorylating carbamate produced
      spontaneously in solution from ammonia and bicarbonate. In contrast, P. abyssi
      CPSase has intrinsic bicarbonate-dependent ATPase activity, suggesting that the
      enzyme can catalyze the phosphorylation of the isosteric substrates carbamate and
      bicarbonate.

PMID- 11523893
TI  - Metallosphaera sedula TA-2, a calditoglycerocaldarchaeol deletion strain of a
      thermoacidophilic archaeon.
AB  - A spherical thermoacidophilic archaeon, strain TA-2, was obtained from acidic hot
      springs located in Ohwaku Valley, Hakone, Japan. This isolate is an obligate
      aerobic chemoorganoheterotroph that grows optimally at about 75 degrees C, pH
      2.8. The G + C content of DNA from TA-2 is 47 mol%. The 16S rRNA gene from TA-2
      showed more than 99% similarity with those of Metallosphaera sedula and
      Metallosphaera prunae and less than 92% similarity with other members of the
      order Sulfolobales. DNA-DNA hybridization experiments showed more than 93%
      genomic DNA homology among TA-2, M. sedula DSM5348T, and M. prunae DSM10039T.
      However, TA-2 lacks calditoglycerocaldarchaeol derivatives, which are usually
      found in the membrane lipids of members of the order Sulfolobales. Therefore,
      calditoglycerocaldarchaeol may not be essential for survival in thermophilic and
      acidophilic environments. The isolate was deposited as Metallosphaera sedula TA-2
      (JCM 9064, IFO 15160).

PMID- 11523894
TI  - Chromosomally encoded arsenical resistance of the moderately thermophilic
      acidophile Acidithiobacillus caldus.
AB  - Arsenical resistance is important to bioleaching microorganisms because these
      organisms release arsenic from minerals such as arsenopyrite during bioleaching.
      The acidophile Acidithiobacillus caldus KU was found to be resistant to the
      arsenical ions arsenate, arsenite, and antimony via an inducible, chromosomally
      encoded resistance mechanism. Because no apparent alteration of the toxic ions
      was observed, Acidithiobacillus (At.) caldus was tested to determine if it was
      resistant as a result of decreased accumulation of toxic ions. Reduced
      accumulation of arsenate and arsenite by induced At. caldus cells supported this
      hypothesis. It was also found that, with the addition of an energy source,
      induced At. caldus could transport arsenate and arsenite out of the cell against
      a concentration gradient. The lack of efflux in the absence of an added energy
      source and in the presence of inhibitors suggested that efflux was energy
      dependent. Induced At. caldus also expressed arsenate reductase activity,
      indicating that At. caldus has an arsenical resistance mechanism that is
      analogous to previously described systems from other Bacteria. Southern
      hybridization analysis showed that At. caldus and other gram-negative acidophiles
      carry an Escherichia coli arsB homologue on the chromosome.

PMID- 11523895
TI  - A novel replication element from an Antarctic plasmid as a tool for the
      expression of proteins at low temperature.
AB  - Genetic manipulation of Antarctic bacteria has been very limited so far. This
      article reports the isolation and molecular characterization of a novel plasmid,
      pMtBL, from the Antarctic gram-negative bacterium Pseudoalteromonas haloplanktis
      TAC 125. This genetic element, 4,081 bp long, appeared to be a multicopy cryptic
      replicon with no detectable transcriptional activity. By an in vivo assay, the
      pMtBL autonomous replication sequence was functionally limited to an AluI plasmid
      fragment of about 850 bp. This novel cold-adapted replication element showed
      quite a broad host range profile: it was cloned into a mesophilic genetic
      construction, obtaining a cold-adapted expression vector that was able to promote
      the production of P. haloplanktis A23 alpha-amylase in a psychrophilic bacterium.
      This study represents the first report of successful recombinant production of a
      cold-adapted protein in an Antarctic host.

PMID- 11523896
TI  - Archaeal RecA homologues: different response to DNA-damaging agents in mesophilic
      and thermophilic Archaea.
AB  - Two archaeal proteins, RadA and RadB, share similarity with the RecA/Rad51 family
      of recombinases, with RadA being the functional homologue. We have studied and
      compared the RadA and RadB proteins of mesophilic and thermophilic Archaea. In
      growing cells, RadA levels are similar in mesophilic Methanococcus species and
      the hyperthermophile Methanococcus jannaschii. Treatment of cells with mutagenic
      agents (methylmethane sulfonate or UV light) increased the expression of RadA (as
      evidenced by higher levels of both mRNA and protein) in all organisms tested, but
      the increase was greater in the mesophiles than in the thermophiles M. jannaschii
      and Sulfolobus solfataricus. Recombinantly expressed RadA proteins from the
      mesophile M. voltae and the thermophile M. jannaschii were similar in their
      ATPase- and DNA-binding activities. All the data are consistent with proposals
      that RadA plays the same role as eukaryotic Rad51. Surprisingly, the data also
      suggested that the thermophiles do not need more RadA protein or activity than
      the mesophiles. On the other hand, RadB is not coregulated with RadA, and its
      role remains unclear. Neither RadA nor RadB from a mesophile or from a
      thermophile rescued the UV-sensitive phenotype of an Escherichia coli recA- host.

PMID- 11523897
TI  - Enzymatic synthesis and hydrolysis of xylogluco-oligosaccharides using the first
      archaeal alpha-xylosidase from Sulfolobus solfataricus.
AB  - The first, recently identified, archaeal alpha-xylosidase from Sulfolobus
      solfataricus (XylS) shows high specificity for hydrolysis of isoprimeverose
      [alpha-D-xylopyranosyl-(1,6)-D-glucopyranose, (X)], the p-nitrophenyl-beta
      derivative of isoprimeverose, and xyloglucan oligosaccharides and has
      transxylosidic activity, forming, in a retaining mode, interesting alpha
      xylosides. This article describes the synthesis of isoprimeverose, the
      disaccharidic repeating unit of xyloglucan, of the p-nitrophenyl-beta derivative
      of isoprimeverose, and of a trisaccharide based on isoprimeverose that is one of
      the trisaccharidic building blocks of xyloglucan. A substrate structure-activity
      relationship is recognized for both the hydrolysis and the synthesis reactions of
      XylS, it being a biocatalyst (i) active hydrolytically only on X-ending
      substrates liberating a xylose molecule and (ii) capable of transferring xylose
      only on the nonreducing end glucose of p-nitrophenyl-(PNP)-beta-D-cellobioside.
      The compounds synthesized by this enzyme are a starting point for enzymological
      studies of other new enzymes (i.e., xyloglucanases) for which suitable substrates
      are difficult to synthesize. This study also allows us to define the chemical
      characteristics of the xylose-transferring activity of this new archaeal enzyme,
      contributing to building up a library of different glycosidases with high
      specific selectivity for oligosaccharide synthesis.

PMID- 11523898
TI  - KATP channel-independent glucose action: an elusive pathway in stimulus-secretion
      coupling of pancreatic beta-cell.

PMID- 11523899
TI  - Regulatory mechanisms of female germ cell apoptosis during embryonic development.

PMID- 11523901
TI  - Immediate-Type allergy against human insulin associated with marked eosinophilia
      in type 2 diabetic patient.
AB  - We describe a type 2 diabetic patient who showed immediate-type allergy against
      human insulin associated with marked eosinophilia at initial insulin therapy.
      Three months after initiation of insulin therapy, he noticed itchy skin wheals at
      the site of the insulin injection. Laboratory data at that time showed marked
      eosinophilia (2,512 /mm3) and progression of renal dysfunction. Skin test with
      semisynthetic human insulin and protamine sulfate resulted in local immediate
      skin reactions such as itchy erythema and wheals. Histopathology of the biopsy
      specimen from skin showed perivascular infiltration of lymphocytes and numerous
      eosinophils in the dermis and subcutaneous fat. Although the titer of total IgE
      antibody was within normal range, that of insulin-specific IgE antibody was high.
      Insulin administration was discontinued to preserve his insulin secretion, and
      stable control of his hyperglycemia was obtained by initiating nateglinide
      treatment (360 mg/day). His itchy skin lesions disappeared within two weeks after
      cessation of the insulin therapy and both eosinophilia and renal dysfunction
      gradually improved. Although the widespread use of human insulin in diabetic
      patients has greatly reduced the incidence of insulin allergy, the possibility of
      human insulin allergy should be kept in mind when initiating such therapy.

PMID- 11523900
TI  - Involvement of the cholinergic pathway in the pathogenesis of pituitary Cushing's
      syndrome.
AB  - Transsphenoidal adenomectomy is currently the first choice for treatment of
      patients with pituitary ACTH-dependent Cushing's syndrome. However,
      pharmacotherapy is prescribed for some patients, e.g., unsuccessful surgery. We
      treated a woman in whom pituitary Cushing's syndrome was improved while she was
      on antimuscarinic cholinergic agents, atropine sulphate and pirenzepine
      hydrochloride. The diminished effect of anticholinergics on ACTH and cortisol was
      incidentally identified in an inferior petrosal sinus sampling procedure. A
      single intramuscular injection of atropine significantly decreased both ACTH
      (43.9 pg/ml to less than 12.0; normal, 12.0-40.0 pg/ml) and cortisol (29.9
      microg/dl to 13.6; normal, 7.6-23.6 microg/dl). An M1-muscarinic receptor
      specific antagonist, pirenzepine hydrochloride, also had a diminishing effect on
      these hormones and this inhibiting effect was partially blocked by the
      simultaneous administration of an anticholinesterase agent, pyridostigmine
      bromide. Chronic oral ingestion of these agents led to improvement in clinical
      symptoms, and urinary 17-hydroxycorticosteroid and 17-ketosteroid levels were at
      normal to upper-normal levels. This is the first documentation of involvement of
      the cholinergic system in the pathogenesis of pituitary Cushing's syndrome.

PMID- 11523902
TI  - Growth hormone and gonadotropin-releasing hormone analog therapy in
      haploinsufficiency of SHOX.
AB  - We report on GH (0.5 IU or 0.17 mg/kg/week) and GnRH analog (GnRHa, 60 microg/kg,
      every 4 weeks) therapy in SHOX haploinsufficiency. Case 1 was a 46,XY boy with
      microdeletion of the Y chromosomal pseudoautosomal region. At 7 years of age, he
      exhibited short stature (-3.9 SD) with a reduced growth rate (3.8 cm/year), short
      4th metacarpals, and mild Madelung deformity. GH therapy resulted in a marked
      increase in height velocity (10.7 cm/year in the first year). Case 2 was a 46,XX
      girl with a heterozygous nonsense mutation of SHOX (C674T). At 6 years of age,
      she presented with short stature (-3.3 SD) with a low height velocity (4.0
      cm/year). GH therapy caused a moderate increase in height velocity (6.6 cm/year
      in the first year and 6.0 cm/year in the second year) before puberty. Because of
      breast development, she received GnRHa from 9 8/12 years of age. At 10 10/12
      years of age, she had mild shortening and borderline curvature of radius. Case 3
      was a girl with a 46,X,der(X)t(X;2)(p22.3;p21) karyotype. She was treated with GH
      from 6 to 14 years of age, and also with GnRHa from 12 to 15 years of age. Her
      height remained around mean -4 SD, with no discernible alteration of height
      velocity. At 17 years of age, she had short stature (-4.1 SD), bilateral cubitus
      valgus, Madelung deformity, and full breast development. The results suggest that
      GH therapy may have variable statural effects in SHOX haploinsufficiency as in
      most disorders including Turner syndrome, and that GnRHa therapy after pubertal
      entry may be insufficient to prevent the development of skeletal lesions such as
      Madelung deformity.

PMID- 11523903
TI  - Painless thyroiditis associated with severe inflammatory reactions in amyloid
      goiter: a case report.
AB  - We report the case of a 64-year-old woman with rheumatoid arthritis (RA)
      associated with high grade fever, malaise, and painless swelling of thyroid
      gland. Laboratory findings showed severe systemic inflammatory reactions,
      including increases in various cytokines such as IL-6. Gallium-67 citrate imaging
      revealed intense uptake in the painlessly enlarged thyroid gland. Histologically,
      biopsied specimens of thyroid showed diffuse amyloid infiltrations, which
      included amyloid A (AA) protein. Biopsies of rectum and stomach revealed similar
      amyloid depositions, indicating that the amyloid had a secondary origin,
      potentially due to RA. All clinical symptoms were relieved by intravenous
      pulsatile administration of methylprednisolone followed by oral prednisone,
      resulting in prolonged hypothyroid status. To our knowledge, this is the first
      case report in Japan describing painless thyroiditis with severe inflammatory
      reactions in amyloid goiter.

PMID- 11523904
TI  - Aldosterone-producing adenoma with prolonged amelioration by dexamethasone.
AB  - Secretion of aldosterone from aldosterone-producing adenoma (APA) is to some
      degree under the control of ACTH and the suppressible effect of glucocorticoid on
      plasma aldosterone concentration (PAC) and blood pressure has been reported to be
      transient. We report a rare case of aldosteronism due to APA in which PAC and
      blood pressure were well controlled with small dose dexamethasone for over one
      year. No chimeric gene of glucocorticoid-remediable aldosteronism (GRA) was found
      in DNA of APA and leukocytes from peripheral blood and 17alpha-hydroxylase
      deficiency (17-OH-D) was ruled out by endocrinological examinations, this case
      indicates the possibility of an unknown mechanism of ACTH-dependent APA.

PMID- 11523905
TI  - Free radical-mediated tolbutamide desensitization of K+ATP channels in rat
      pancreatic beta-cells.
AB  - To study the effects of hydroxyl radicals on the sensitivity of the ATP-sensitive
      K+ (K+ ATP) channel to tolbutamide, we used patch clamp and microfluorometric
      techniques in pancreatic beta-cells isolated from rats. cell-attached membrane
      patches, exposure of the cells to 0.3 mM H2O2 increased the probability of
      opening of K+ATP channels in the presence of 2.8 mM glucose. Tolbutamide dose
      dependently inhibited the K+ATP channel with half-maximal inhibition (IC50) at
      0.8 microM before and immediately after exposure to H2O2. After prolonged
      exposure (>20 min) to H2O2, the IC50 was increased to 15 microM. The presence of
      both ATP and ADP at concentrations ranging from 0.01 to 0.1 mM in the inside-out
      bath solution significantly enhanced the inhibition of the channels by 10 microM
      tolbutamide. Addition of 0.3 mM H2O2 induced a transient minute increase in the
      cytoplasmic Ca2+ concentration ([Ca2+]i) within 10 min, followed by a sustained
      pronounced increase in [Ca2]i. After more than 20 min of exposure of cells to
      0.3mM H2O2, [Ca2]i was increased to above 2 microM. Treatment of the cytoplasmic
      face of inside-out membrane patches with 1 microM Ca2+ attenuated the tolbutamide
      sensitivity of the K+ATP channel, but not the ATP-sensitivity of the channel.
      These findings indicate that H2O2 reduces tolbutamide sensitivity by inducing a
      sustained increase in [Ca2+]i.

PMID- 11523906
TI  - Serum concentration of androstenediol and androstenediol sulfate in patients with
      hyperthyroidism and hypothyroidism.
AB  - Androstenediol (5-androsten-3beta, 17beta-diol, ADIOL) and androstenediol 3
      sulfate (ADIOLS) are active metabolites of dehydroepiandrosterone (DHEA) and DHEA
      sulfate (DHEAS), respectively, and have estrogenic activity and immunoregulatory
      function. We examined serum concentrations of ADIOL, ADIOLS, DHEA, DHEAS and
      pregnenolone sulfate (5-pregnen-3beta-ol-20-one sulfate, PREGS) in patients with
      Graves' thyrotoxicosis (male/female 9/14), hypothyroidism (11/20) and in normal
      controls (14/29). In hypothyroidism serum levels of all these steroids were
      significantly decreased in both genders. In hyperthyroidism, in contrast, serum
      levels of ADIOLS (male 1.49 +/- 0.69, female 0.64 +/- 0.31 micromol/l), DHEAS
      (male 7.43 +/- 3.91, female 5.13 +/- 2.03 micromol/l), and PREGS (male 1.13 +/-
      0.58, female 1.07 +/- 0.85 micromol/l) were markedly increased, but serum
      concentrations of ADIOL and DEHA were not significantly different from controls
      (ADIOLS male 0.36 +/- 0.33, female 0.14 +/- 0.09 micromol/l; DHEAS male 2.88 +/-
      1.70, female 1.86 +/- l1.03pmol/l; PREGS male 0.18 +/- 0.12, female 0.11 +/- 0.08
      micromol/l; ADIOL male 3.76 +/- 1.35, female 1.91 +/- 1.17 nmol/l; DHEA male 9.23
      +/- 3.49, female 13.5 +/- 10.8nmol/l). Serum concentrations of all these steroids
      correlated with the serum concentration of the thyroid hormones in these
      patients. Serum albumin and sex hormone-binding globulin concentrations were not
      related to these changes in the concentrations of steroids. These findings
      indicate that serum concentrations of ADIOLS, ADIOL, DHEAS, DHEA and PREGS were
      decreased in hypothyroidism, whereas serum ADIOLS, DHEAS and PREGS concentrations
      were increased but ADIOL and DHEA were normal in hyperthyroidism. Thyroid hormone
      may stimulate the synthesis of these steroids and sulfotransferase is speculated
      to be increased in hyperthyroidism. Increased ADIOLS might contribute to
      menstrual disturbances and gynecomastia in hyperthyroidism.

PMID- 11523907
TI  - Development of growth hormone and adrenocorticotropic hormone deficiencies in
      patients with prenatal or perinatal-onset hypothalamic hypopituitarism having
      invisible or thin pituitary stalk on magnetic resonance imaging.
AB  - A gradual loss of anterior pituitary hormones is suspected in patients treated
      with irradiation due to brain tumors. Development of growth hormone deficiency
      (GHD) with age has been documented in patients with idiopathic GHD. A gradual
      loss of adrenocorticotropic hormone (ACTH) secretion has been also shown in a
      patient with severe GHD and an invisible pituitary stalk on magnetic resonance
      imaging (MRI). The purpose of this longitudinal and cross-sectional study was to
      evaluate the gradual loss of growth hormone (GH) and ACTH in a homogeneous group
      of patients with hypopituitarism. Twenty-eight patients (23 males, 5 females)
      from four hospitals were diagnosed as having prenatal or perinatal-onset
      hypothalamic hypopituitarism. They had an abnormal pituitary stalk on MRI
      (invisible in 18 patients, thin in 10 patients) without any other organic disease
      of the brain. Each patient had GHD upon initial evaluation. Height (n=20) was
      analyzed as standard deviation score (SDS). Longitudinal (n=8) and cross
      sectional (n=28) GH secretion capacity was evaluated by GH peaks, in response to
      insulin tolerance test (ITT) and growth hormone releasing factor test (GRF test).
      Longitudinal (n=10) and cross-sectional (n=28) ACTH secretion capacity was
      evaluated by cortisol peaks in response to ITT. Height SDS decreased each year in
      all the untreated patients after birth. GH peaks decreased gradually with age.
      Longitudinal data showed decreased GH peaks with age in seven out of eight
      patients using ITT and in all four patients using GRF tests. Cortisol peaks also
      decreased gradually together with signs and symptoms for adrenal deficiency such
      as general fatigue. Cortisol peaks of less than 414 nmol/L (15 microg/dl) in
      response to ITT were seen in 24% of the tests before age 10 and 56% before age
      25. In conclusion, GHD and ACTH deficiency developed gradually in patients with
      prenatal or perinatal-onset hypothalamic hypopituitarism who had invisible or
      thin pituitary stalks examined by MRI.

PMID- 11523908
TI  - An ectopic ACTH-producing carcinoid tumor localized by the measurement of ACTH in
      the bronchial lavage.
AB  - We report a case of an ectopic ACTH-producing carcinoid in the lung. Typical
      Cushingoid appearance, elevated plasma ACTH and serum cortisol, bilateral
      enlargement of the adrenal glands, absence of pituitary adenoma and negativity in
      petrosus sinus venous sampling indicated the ectopic ACTH syndrome. Venous
      samplings from a lung tumor which was detected by the chest X-ray, did not show
      any step-up of ACTH. However, ACTH concentration in the bronchoscopic lavage was
      as high as that in the peripheral blood. Removal of the tumor, which was an ACTH
      producing carcinoid, resulted in normalization of ACTH and cortisol
      concentrations. Measurement of ACTH in the bronchoscopic lavage was useful for
      the diagnosis of ectopic ACTH-producing tumor.

PMID- 11523909
TI  - ATP-Sensitive potassium channels modulate glucose transport in cultured human
      skeletal muscle cells.
AB  - Several lines of evidence suggest that ATP-sensitive potassium (KATP) channels
      are involved in glucose uptake by insulin target tissues. The aim of the present
      study was to prove directly the effect of KATP channel activity on glucose
      transport into cultured human skeletal muscle cells. We used potassium channel
      openers PCO-400 and nicorandil alone or in combination with channel blockers
      glibenclamide and gliclazide to examine their effects on insulin- or high glucose
      concentration-induced glucose uptake using 2-deoxy-D-3H-glucose or 3-O-methyl-D
      3H-glucose as tracer, respectively. PCO-400 inhibited the basal (non-stimulated)
      uptake of 2-DG or 3-OMG at the glucose concentration of 5 mM. PCO-400 and
      nicorandil dose-dependently inhibited insulin-stimulated glucose uptake, and
      their inhibitory effects were reversed by glibenclamide or gliclazide. In
      addition, PCO-400 inhibited high glucose concentration-facilitated glucose
      transport in the absence of insulin, and this effect was also antagonized by both
      sulfonylurea drugs. Regarding the mechanism by which KATP channels modulate
      glucose transport, we focused on protein kinase C (PKC), because PKC has been
      supposed to participate in both insulin- and high glucose concentration
      stimulated glucose transport. PMA (phorbol 12-myristate 13-acetate) dose
      dependently reversed the PCO-400-induced suppression of insulin-stimulated
      glucose uptake. On the other hand, PCO-400 at the concentration that inhibited
      glucose uptake caused no alteration of membrane-associated PKC activity in the
      presence of insulin or PMA. From these results we conclude that KATP channels
      modulate the basal and insulin-or high glucose level-stimulated glucose transport
      in skeletal muscle through a mechanism independent of PKC.

PMID- 11523910
TI  - The influence of long-term different diabetic therapies on plasma leptin in type
      2 diabetic subjects.
AB  - The aim of this study was to assess the effect of the long-term different
      diabetic therapies on the plasma leptin level in type 2 diabetic subjects. We
      measured plasma leptin, body fat and fasting plasma insulin in 96 type 2 diabetic
      male subjects. They had received the same treatment regimen for more than one
      year (3.5 +/- 2.3 years, mean +/- SD) and were weight-stable over the previous
      three months. The distribution was as follows: diet control group: 32, oral
      hypoglycemic agent (OHA) group: 32, and insulin group: 32. The results showed
      that the plasma leptin level of the different therapy groups was all positively
      correlated with body fat. The fasting insulin levels were significantly higher (p
      < 0.0001) in the insulin group than those in the other two groups. The fasting
      insulin of the OHA group was also greater than that of the diet group but was not
      statistically significant. The leptin concentrations were significantly higher in
      the insulin group (p < 0.001) and OHA group (p = 0.0082) than that in the diet
      group. The leptin concentrations of insulin group were also significantly higher
      (p = 0.0021) than that of the OHA group. Stepwise multiple regression analysis
      revealed that the significant differences in the leptin level of whole group was
      mainly affected by fasting insulin (p < 0.0001), followed by fat percentage (p =
      0.001), fat distribution (p = 0.009) and fasting sugar (p = 0.02), whereas there
      was no association of leptin with age, height, glycosylated hemoglobin A1c,
      lipid, or blood pressure. We concluded that long-term different diabetic
      therapies may affect the plasma leptin level, which is mediated mainly by insulin
      changes. This insulin effect is independent of body fat and may be superior to
      the fat effect on plasma leptin in the type 2 diabetic patients.

PMID- 11523911
TI  - A case of thyrotoxicosis with pancytopenia.
AB  - We report a 49-year-old man with primary hyperthyroidism who presented with
      pancytopenia. The patient presented with leg edema, sinus tachycardia,
      cardiomegaly, and pleural effusions, all from congestive heart failure.
      Laboratory data showed pancytopenia and primary hyperthyroidism; echocardiogram
      showed diffuse hyperkinesis of the left ventricular wall and right ventricular
      overloading. The bone marrow was moderately hypercellular and compatible with
      arrested hematopoiesis. Pancytopenia and heart failure improved after
      administration of methimazole and diuretics. However, high levels of thyroid
      hormone recurred with pancytopenia 4 months after admission. Therefore, subtotal
      thyroidectomy was performed, and the levels of thyroid hormones and peripheral
      blood cell counts have remained normal. Pancytopenia may be caused by
      hyperthyroidism.

PMID- 11523912
TI  - Glutamate is not a major conveyer of ATP-sensitive K+ channel-independent glucose
      action in pancreatic islet beta cell.
AB  - Insulinotropic action of glucose can be categorized as 1) triggering of release,
      2) augmentation of exocytosis elicited by Ca2+, and 3) time-dependent
      potentiation (TDP) of the exocytotic machinery. Glucose-induced closure of ATP
      sensitive K+ (K+ATP) channel is required for the first but not for the latter
      two. We examined the legitimacy of a novel hypothesis that glutamate is a
      conveyer of the K+ATP channel-independent glucose action, using intact rat
      pancreatic islets. To this end, we compared glucose and cell permeable glutamate
      donors such as dimethylglutamate and glutamine for their potency of augmentation
      and TDP in the presence of diazoxide (250 micromol/l), a K+ATP channel opener.
      One millimolar leucine was employed as an activator of glutamate dehydrogenase
      (GDH) as needed. A high concentration (16.7 mmol/l) of glucose applied
      simultaneously with a depolarizing concentration (50 mmol/l) of K+ augmented
      (5.80 fold) insulin release elicited by the latter. Pretreatment of the islets
      with 16.7 mmol/l glucose caused TDP so that insulin release subsequently elicited
      by 50 mmol/l K+ alone was enhanced (4.70 fold). The augmentation and TDP caused
      by dimethylglutamate and glutamine (10 mmol/l each), respectively, were very weak
      (12% of the glucose effect utmost), and dramatically enhanced upon activation of
      GDH by leucine. Insulinotropic effect of the glutamate donors, but not that of 50
      mmol/l K+, was eliminated by 2 mmol/l NaN3, a mitochondrial poison. Glutamate per
      se serves as a weakly metabolizable mitochondrial fuel, but not a direct conveyer
      of the K+ATP channel-independent glucose action in the islet beta cell.

PMID- 11523913
TI  - Expression of prolactin-releasing peptide in human placenta and decidua.
AB  - The aims of this study were to determine whether the human placenta and decidua
      express PRL-releasing peptide (PrRP) mRNA and whether PrRP regulates PRL
      secretion from cultured human decidual cells. PrRP gene expression was analyzed
      by reverse transcription (RT)-PCR, and the level of the gene expression was
      quantified by a ribonuclease protection assay. PrRP gene expression was detected
      in both the placenta and decidua. These tissues expressed PrRP mRNA throughout
      pregnancy and the level of PrRP mRNA expression somewhat increased during
      midpregnancy. Placental and decidual cells also expressed PrRP mRNA, in vitro. To
      determine whether PrRP affects decidual PRL secretion, human endometrial stromal
      cells and decidual cells were cultured and treated with or without 1 microM
      PrRP31. PrRP31 did not affect PRL secretion in either short or long term
      incubation. Moreover, the RT-PCR analysis indicated that human decidua does not
      express the PrRP receptor, hGR3, mRNA. These findings suggest that PrRP produced
      by the human placenta and decidua does not affect decidual PRL secretion due to a
      lack of the receptor, and that it may play other roles during pregnancy.

PMID- 11523914
TI  - Plasma brain natriuretic peptide concentration in patients with Graves' disease.

PMID- 11523915
TI  - Biology, life table and host specificity of the mushroom pest, Brennandania lambi
      (Acari: Pygmephoroidea).
AB  - Biology and life table parameters of Brennandania lambi (Krczal) were studied at
      different temperatures while feeding on white mushroom (Agaricus bisporus)
      mycelium cultured on mushroom compost. The duration of egg and larva development,
      preoviposition and oviposition period, female longevity, and the time to 50%
      mortality declined as temperature increased from 16 to 28 degrees C. The
      threshold temperature of development (female) was 9 degrees C and the thermal
      constant for completion of development (female) was 195 day-degrees. At 16, 20.
      24 and 28 degrees C, the total fecundity (eggs/female) was 71, 67, 66 and 57,
      respectively and the daily fecundity rate (eggs/female/day) was 5.6, 8.7, 8.7 and
      9.1, respectively. The sex ratio (female/male) ranged from 1.9 to 2.1 at 16-28
      degrees C. At 16, 20, 24 and 28 degrees C, the intrinsic rate of natural increase
      (rm) was 0.11, 0.18, 0.22 and 0.27, respectively, and the population doubling
      time was 6.1. 3.9. 3.2 and 2.5 days, respectively. All life stages of the mite
      died when exposed to 35 degrees C constant temperature for 24h. or to 32 degrees
      C constant temperature for 12 days or to 31-35 degrees C (average 32.9 degrees C)
      ambient temperature for 4 days. Brennandania lambi completed development only
      when fed on Ag. bisporus mycelium growing on mushroom compost. It could not
      survive on mushroom mycelia of Auricularia auricula. Au. polytricha, Ganoderma
      lucidum, Hericium erinaceus, Lentinus edodes, Pleurotus ostreatus, P. sajor-caju
      and Tremella juciformis.

PMID- 11523916
TI  - The occurrence of mites in cereal-based foods destined for human consumption and
      possible consequences of infestation.
AB  - Seven categories of cereal-based food products purchased at food retail outlets
      in UK were examined for the presence of mites by analysing 20 g samples using a
      flotation method. Mites were found in 21% of 571 samples, which were examined
      soon after purchase, and in 38% of 421 samples, derived from the 571 samples
      which were examined after 6 weeks of storage in volunteers' homes. Most of the
      samples where mites were detected had fewer than five mites. However, a few
      samples contained more than 20 mites with a maximum of 428 mites detected in a
      single sample. Sixteen families, genera or species of mites were recovered. The
      most common species were Acarus siro. Tyrophagus putrescentiae, Lepidoglyphus
      destructor and Glycyphagus domesticus. The level of contamination was broadly
      similar for each of the seven categories of products examined. It is likely that
      infestation occurs at every stage of food processing and storage. This is the
      first study of its kind and there is no reason to believe that results from
      similar studies carried out in other temperate countries would be markedly
      different. Increase in the percentage of contaminated samples following storage
      in a domestic situation suggests that the domestic environment is an important
      factor in developing infestation. The implications of mite contamination on food
      quality and on human health are briefly discussed.

PMID- 11523917
TI  - How species-specific is the phoretic relationship between the broad mite,
      Polyphagotarsonemus latus (Acari: Tarsonemidae), and its insect hosts?
AB  - Broad mite, Polyphagotarsonemus latus (Acari: Tarsonemidae), is a serious plant
      pest in tropical and subtropical regions. Phoretic associations between broad
      mite and two genera of whiteflies (Insecta: Homoptera: Aleyrodidae). namely
      Bemisia and Trialeurodes, have been reported from different parts of the world.
      Our purpose was to determine the specificity of the association between the mite
      and its phoretic hosts. Two host plants, potatoes and cucumbers, were used to
      study these relationships in the laboratory. Insects frozen for 24 h were used as
      potential phoretic hosts in all experiments. Attachment levels were monitored by
      counting the number of mites attached to each insect. All tests were conducted
      for 4-6 h. as attachment to Bemisia tabaci on potato shoots leveled off after 4
      h, increasing only marginally after 8 h. Attachment levels to thrips (the western
      flower thrips, Frankliniella occidentalis) and to allate aphids (Myzus persicae)
      was negligible relative to the attachment to B. tabaci. Broad mite also attached
      to the whiteflies Dialeurodes citri, Aleyrodes singularis and Trialeurodes lauri,
      the latter being the least attractive species (including B. tabaci). Washing B.
      tabaci with pentane greatly reduced attachment. Using cucumbers as hosts did not
      substantially change the general trend, but attachment levels were lower. The
      phoretic relationship between broad mite and its insect hosts appears to be
      specific to whiteflies, with some whiteflies having a higher potential as
      phoretic hosts.

PMID- 11523918
TI  - Distortion of the spermathecae of phytoseiid mites (Acari: Phytoseiidae) in slide
      preparation.
AB  - The shape and dimensions of the spermathecae are taxonomically important
      characteristics in phytoseiid mites. In experiments with Neoseiulus californicus
      (McGregor) and Typhlodromus pyri Scheuten, the shape of the cervix of the
      spermatheca changed considerably and its diameter was increased by 42-49% when
      mites were flattened, compared to being mounted with 140 microm spacers
      underneath the coverslips. Dimensions of the dorsal shield were also affected by
      flattening. increasing by 3-5%.

PMID- 11523919
TI  - Purification and characterization of aspartate aminotransferase from developing
      embryos of the camel tick Hyalomma dromedarii.
AB  - Aspartate transaminase (AST) activity in the camel tick Hyalomma dromedarii was
      followed throughout embryogenesis. During purification of AST to homogeneity, ion
      exchange chromatography lead to four separate forms (termed I, II, III and IV).
      AST II with the highest specific activity was pure after chromatography on
      Sephacryl S-300. The molecular mass of AST II was 52 KDa for the native enzyme,
      composed of one subunit of 50 KDa. AST II had a Km value of 0.67mM for a
      ketoglutarate and 15.1 mM for aspartate. AST II had a pH optimum of 7.5 with heat
      stability up to 50 degrees C for 15 min. The enzyme was activated by MnCl2, and
      inhibited by CaCl2, MgCl2. NiCl2, and ZnCl2.

PMID- 11523920
TI  - Evidence for the utility of the Bm86 antigen from Boophilus microplus in
      vaccination against other tick species.
AB  - The Bm86 antigen, as originally identified in Boophilus microplus, is the basis
      of commercial tick vaccines against this tick species. The potential for using
      this antigen or homologues of the antigen in vaccination against other tick
      species has been assessed. We have conducted vaccine trials in cattle using the
      B. microplus-derived recombinant Bm86 vaccine (TickGARD) using pairs of
      vaccinated calves and control calves. These were infested with B. microplus and
      Boophilus decoloratus larvae simultaneously. For both species, the numbers of
      engorged female adult ticks, their weight and egg-laying capacity were all
      reduced, leading to a reduction in reproductive capacity of 74% for B. microplus
      and 70% for B. decoloratus. Hyalomma anatolicum anatolicum ticks were fed both as
      immatures as well as adults on vaccinated calves and non-vaccinated controls.
      There was an overall 50% reduction in the total weight of nymphs engorging on
      vaccinated calves, and a suggestion of a subsequent effect on feeding adults. For
      Hyalomma dromedarii there was a 95% reduction in the number of nymphs engorging
      and a further 55% reduction in weight of those ticks surviving. Rhipicephalus
      appendiculatus and Amblyomma variegatum ticks were fed simultaneously both as
      immatures and subsequently as adults. There was no evidence for a significant
      vaccination effect. Finally, the amino acid sequence of a Bm86 homologue found in
      H. a. anatolicum unequivocally demonstrated the conservation of this molecule in
      this species. Our strategy for the development of multivalent anti-tick vaccines
      is discussed in relation to these findings.

PMID- 11523921
TI  - Ornithodoros porcinus ticks, bushpigs, and African swine fever in Madagascar.
AB  - African swine fever (ASF) has recently made its appearance in Madagascar. Ticks
      of the Ornithodoros moubata group, considered to be O. porcinus Walton, 1962 were
      formerly known to occur in western Madagascar, but seem to have disappeared from
      that region. However, three new sites where they occur were found in the humid
      and cool central highlands of Anatananarivo province. These ticks are known to be
      efficient reservoirs and vectors of ASF and constitute a considerable
      complication to the control of the disease. The authors also discuss another
      potentially complicating factor, the presence of a species of African bushpig,
      Potamochoerus larvatus.

PMID- 11523922
TI  - Mobile phones and your health.

PMID- 11523923
TI  - Timely topic: Premalignant lesions associated with adenocarcinoma of the upper
      gastrointestinal tract.
AB  - The changing incidence of adenocarcinomas, particularly in the oesophagus and
      gastric cardia, has led to the rapid expansion of screening programmes aimed at
      detecting the precursor lesion of dysplasia before adenocarcinoma develops. The
      pathologist now has an important role in first diagnosing patients at risk for
      developing dysplasia, and then correctly classifying dysplasia when it occurs.
      Barrett's oesophagus has had different diagnostic criteria in previous years but
      is currently diagnosed by the presence of intestinal metaplasia of any length in
      the true oesophagus. Intestinal metaplasia confined only to the gastro
      oesophageal junction or cardia is of uncertain significance but is probably
      common, with less risk of progressing to dysplasia or malignancy. In the stomach,
      patients with autoimmune atrophic gastritis and Helicobacter-associated
      multifocal atrophic gastritis have an increased risk of adenocarcinoma, but
      screening protocols are not well-developed compared with those used for Barrett's
      oesophagus. Dysplasia of glandular epithelium can be classified using well
      described criteria. Low grade dysplasia is the most common type and regresses or
      remains stable in the majority of patients. High grade dysplasia is more ominous
      clinically, with a propensity to coexist with or progress to adenocarcinoma.

PMID- 11523924
TI  - Suggestions for HER-2/neu testing in breast carcinoma, based on a comparison of
      immunohistochemistry and fluorescence in situ hybridisation.
AB  - The arrival of Herceptin (Trastuzumab), an antibody against the HER-2 oncogene
      found in a proportion of breast carcinomas and other carcinomas, has emphasised
      the need for a standardised technique for demonstrating overexpression of HER-2.
      We compared the Dako A485 antibody and Dako HercepTest kit (HT) on a series of
      122 breast carcinomas. Fluorescence in situ hybridisation (FISH) (Vysis) was
      performed on all cases with positive or equivocal immunohistochemical results.
      The Dako A485 showed HER-2 overexpression in 53% of carcinomas, while the HT
      showed 21% positive (HT 2+ 8%, HT 3+ 13%) and 79% negative (HT 0 67%, HT 1+ 12%).
      FISH for HER-2 gene amplification on all the HT 1+ and HT 2+ cases was negative,
      whereas FISH analysis of all HT 3+ cases was positive, with the exception of one
      case which could not be analysed for technical reasons. When histological subtype
      was analysed, only grade 3 infiltrating duct carcinomas were FISH-positive,
      suggesting that histological grading and subtyping may be able to triage
      carcinomas suitable for HER-2 testing. We suggest that the HT or a similar
      standardised immunohistochemical study for HER-2 can be used to screen breast
      carcinomas. We then recommend FISH where the carcinoma is HT 2+. FISH may also be
      appropriate in high grade, HT 1+ carcinomas where there are doubts regarding
      optimal tissue fixation or block storage conditions.

PMID- 11523925
TI  - pS2 expression in infiltrating ductal carcinoma of the breast correlates with
      oestrogen receptor positivity but not with histological grade and lymph node
      status.
AB  - This investigation was carried out to gain insight into the prevalence of pS2
      expression in invasive ductal breast carcinoma in the Malaysian population and
      its correlation with oestrogen receptor (ER) protein expression and tumour
      aggressiveness. Seventy consecutive infiltrating ductal breast carcinomas treated
      with mastectomy and axillary lymph node clearance were investigated, using the
      standard avidin-biotin complex immunoperoxidase method with microwave antigen
      retrieval and commercial monoclonal antibodies (Dako), for expression of pS2 and
      human ER. This was correlated against histological grade (modified Bloom and
      Richardson) and the presence of axillary lymph node metastasis of these
      carcinomas. Four (5.7%) were grade 1, 40 (57.1%) grade 2 and 26 (37.1%) grade 3
      tumours. A total of 45 (64%) showed histological evidence of axillary lymph node
      metastasis. Forty (57%) were ER-positive, while 31 (44%) were pS2-positive. There
      was a statistically significant correlation between pS2 and ER expressions (chi2
      test with Yates correction: P<0.005). There was no correlation between pS2
      expression and histological grade (P>0.1) and the presence of lymph node
      metastasis (P>0.1). Our findings support the views that pS2 may be a co-marker of
      endocrine responsiveness in invasive breast cancer and that it does not influence
      breast cancer biology in terms of potential for metastatic spread.

PMID- 11523926
TI  - Distinctive microvillous brush border staining with HBME-1 distinguishes pleural
      mesotheliomas from pulmonary adenocarcinomas.
AB  - HBME-1 is an antimesothelial monoclonal antibody that recognises an unknown
      antigen on microvilli of mesothelioma cells. The aim of this study was to
      evaluate the staining pattern with respect to antibody dilution, cellular
      distribution and intensity of immunohistochemical staining with HBME-1 in pleural
      mesotheliomas compared with pulmonary adenocarcinomas. A total of 27 pulmonary
      adenocarcinomas and 26 mesotheliomas were stained with commercially available
      HBME-1 at various antibody dilutions and evaluated for the site (membranous, +/-
      microvillous brush border or cytoplasmic), intensity and percentage of cells
      staining. On light microscopy, 23 mesotheliomas showed distinctive microvillous
      brush border staining with HBME-1 (three mesotheliomas--two sarcomatoid and one
      poorly differentiated--were negative). Twenty-five adenocarcinomas showed
      membranous +/- cytoplasmic staining but lacked the distinctive microvillous brush
      border staining. In a subgroup of tumours studied by electron microscopy
      following immunogold labelling by HBME-1, all of 16 mesothelioma cases showed
      strong immunogold labelling in the membranes of the long microvilli. In contrast,
      the 12 cases of pulmonary adenocarcinomas showed minimal labelling in the
      membranes of the short microvilli, but staining was seen within vesicles, often
      near the surface of the cells. This study shows that the presence of a
      distinctive microvillous brush border by immunohistochemical staining with HBME-1
      allows distinction between pleural mesotheliomas and pulmonary adenocarcinomas
      (sensitivity of 88%, specificity of 100%). The difference in the ultrastructural
      distribution of immunogold labelling with HBME-1 between mesotheliomas and
      adenocarcinomas underscores the light microscopy findings.

PMID- 11523927
TI  - The accuracy and interobserver reproducibility of endometrial dating.
AB  - Although controversial, diagnosis of luteal phase defect (LPD) includes the
      morphological assessment of endometrial development. This study was conducted to
      determine if refresher training in the histological criteria could improve the
      accuracy and interobserver reproducibility of endometrial dating. Seventy-eight
      endometrial biopsies were dated by a reference panel of two pathologists and then
      reviewed twice by a study panel of four pathologists. In the first review, usual
      practice was applied. Prior to the second review, they studied a standard
      document of histological criteria. Samples were dated as proliferative, secretory
      (post-ovulatory day, POD), menstrual, and undatable. Accuracy levels based on the
      reference dating and agreement levels using kappa values were calculated per
      review and compared. The kappa for overall dating was 0.683 in the first review
      and 0.696 in the second. The respective first and second review kappa values were
      0.736 and 0.771 for proliferative, and 0.794 and 0.764 for secretory. Amongst
      those dated as secretory in the first and second reviews, respectively, 31 and
      28% were assigned the same POD by any two panellists, 68 and 63% were dated to
      within 1 day, and 77 and 71% were dated to within 2 days. Accuracy levels per
      panellist for overall dating were very high in both reviews but were low for
      individual PODs. Accuracy and interobserver reproducibility were unaffected by
      refresher training, suggesting the limits of histological dating have been
      reached.

PMID- 11523928
TI  - The immunoexpression of Tn, sialyl-Tn and T antigens in chronic active gastritis
      in relation to Helicobacter pylori infection.
AB  - The simple mucin-type carbohydrate antigens Tn, sialyl-Tn and T represent the
      mucin core oligosaccharide structures that are produced in the initial steps of
      mucin biosynthetic pathway. Utilising monoclonal antibodies anti-Tn antigen, anti
      sialyl-Tn antigen and anti-T antigen, we have investigated the expression of the
      simple mucin-type carbohydrate antigens in 47 biopsy specimens of antral mucosa
      with chronic active gastritis, 25 of which had Helicobacter pylori infection. The
      Tn immunoreactivity, localised at the supranuclear region of surface and
      glandular mucous cells, was observed in all samples, independently from H. pylori
      status. The sialyl-Tn antigen, mainly localised in the cytoplasm of glandular
      mucous cells and in goblet cells vacuoles, was seen in 56% of the cases with H.
      pylori infection and in 41% of the cases in the H. pylori-negative group. In
      addition, the T antigen was found in the cytoplasm of surface and glandular
      mucous cells in 16% of the H. pylori-positive group, whereas the percentage of
      positive cases was reduced to 5% in H. pylori-negative patients, with an
      exclusive localisation in the cytoplasm of glandular mucous cells; after
      neuraminidase treatment, the percentage of T antigen-positive cases was increased
      to 28% in H. pylori-positive cases and to 27% in negative cases. No significant
      relationships between H. pylori infection and Tn, sialyl-Tn or T antigen
      immunoexpression were encountered in our cases. Therefore, we maintain that the
      inflammatory infiltrate may itself play an important role in the expression of
      simple mucin-type carbohydrate antigens in chronic active antral gastritis.

PMID- 11523929
TI  - A comparison of the patterns of laminin expression in fibroadenoma, fibrocystic
      diseases, pre-invasive and invasive ductal breast carcinoma.
AB  - The basement membrane (BM), of which laminin is a major glycoprotein component,
      is an important barrier to tumour cells which must be breeched before metastatic
      spread can occur. We have compared the pattern of laminin expression in a range
      of benign and malignant breast lesions to better understand the process of tumour
      progression. A total of 162 cases of breast samples, comprising 18 fibroadenomas,
      22 cases of fibrocystic disease, 96 cases of invasive ductal carcinoma and 26
      carcinomas with intraductal components, were evaluated for laminin expression by
      a standard immunoperoxidase method on formalin-fixed, paraffin-embedded
      histological sections, using a commercial antibody against human laminin. The
      pattern of laminin expression was charted as follows: Type I, > 70% of BM
      complete/continuous; Type II, > 70% of BM moderately disrupted; Type III, > 70%
      of BM completely disrupted. The Type I pattern was observed in all cases of
      fibroadenoma and fibrocystic diseases, and in 77% of intraductal carcinoma
      components. Various patterns of BM disruption were observed in invasive ductal
      carcinoma. Severity of BM disruption correlated with histological grade of the
      carcinomas (P < 0.001). Small-sized tumours, those without lymphatic invasion and
      lymph node-negative tumours showed more complete patterns of laminin expression.
      The current study suggests that tumour cells with high histological grade possess
      an enhanced capacity to disrupt the basement membrane, an important step in the
      metastatic process. The detection of BM disruption by immunohistochemical
      staining for laminin is technically easy and may be usefully applied for the
      differentiation of in situ and microinvasive carcinoma.

PMID- 11523930
TI  - Isolated dissection of the coronary artery: a postmortem study of seven cases.
AB  - We present the clinical and postmortem findings in seven adults (four females and
      three males), who died with dissection of the coronary arteries. The median age
      was 56 years. Five of the coronary artery dissections (CADs) were spontaneous and
      two followed trauma: one a motor vehicle accident, the other occurred during
      angiography. Four cases died suddenly or within 30 minutes. Three had symptoms of
      at least 24 hours duration and, not unexpectedly, had histological evidence of
      myocardial infarction. Four dissections involved the left anterior descending
      coronary artery, two the right coronary artery and one a dominant circumflex
      artery. Histological examination of the dissected arteries in four cases
      demonstrated necrosis of the medial smooth muscle which was intimately related to
      intimal tears and/or an inflammatory reaction. From a review of the literature
      and this study of seven cases, we conclude that CAD is multifactorial in
      causation and has a wide spectrum of clinical presentations. Presently the role
      of coronary vasospasm and prior trauma appears underestimated, and in many cases
      of CAD the nature of the primary initiating event remains open to speculation.

PMID- 11523931
TI  - Squamous cell carcinoma in situ arising in inflammatory cloacogenic polyps:
      report of two cases with PCR analysis for HPV DNA.
AB  - Inflammatory cloacogenic polyp (ICP) is regarded as part of the spectrum of
      pathological changes encountered in mucosal prolapse syndrome (MPS)/solitary
      rectal ulcer. We present the clinicopathological features of two females with
      squamous cell carcinoma in situ arising in their ICPs. Human papillomavirus (HPV)
      type 16 was demonstrated in the areas of squamous carcinoma in situ in both
      polyps by polymerase chain reaction. These cases highlight the need for close
      scrutiny of the squamous components of these lesions.

PMID- 11523932
TI  - Solitary fibrous tumour of the oral cavity: report of two cases.
AB  - The solitary fibrous tumour is an uncommon, benign neoplasm of adults involving
      the pleura. It is now recognised to occur in extrapleural sites. Only a limited
      number of cases have been reported in the oral cavity. This paper reports two
      further cases, which presented as clinically benign masses in the palate and
      buccal mucosa respectively.

PMID- 11523933
TI  - Small atypical leiomyomas: report of two cases.
AB  - We describe two small atypical leiomyomas. The first was a 6-mm de novo lesion in
      a 53-year-old woman. The second was a 3-mm focus in a 12-mm leiomyoma in a 45
      year-old woman. Both lesions showed moderate atypia and a mitotic rate of six per
      10 high-power fields. Coagulative necrosis was not seen. Neither patient had
      received exogenous oestrogen or progestogen. There was no evidence of recurrence
      or metastasis in either patient after 60 months of follow-up. Our report provides
      evidence that atypical uterine leiomyomas may arise either de novo or within a
      leiomyoma.

PMID- 11523934
TI  - Broadsheet: Clinical and laboratory features of rubella.

PMID- 11523935
TI  - Broadsheet: Biochemical markers of coronary heart disease.

PMID- 11523936
TI  - Effect of global system for mobile communication (gsm)-like radiofrequency fields
      on vascular permeability in mouse brain.
AB  - The effect of global system for mobile communication (GSM) radiofrequency fields
      on vascular permeability in the brain was studied using a purpose-designed
      exposure system at 898.4 MHz. Mice (n= 30) were given a single far field, whole
      body exposure for 60 minutes at a specific absorption rate of 4 W/kg. Control
      mice were also sham-exposed (n = 10) or permitted free movement in a cage (n =
      10) to exclude any stress-related effects. Vascular permeability changes were
      detected using albumin immunohistochemistry and the efficacy of this vascular
      tracer was confirmed with a positive control group exposed to a clostridial toxin
      known to increase vascular permeability in the brain. No significant difference
      in albumin extravasation was detected between any of the groups at the light
      microscope level using the albumin marker.

PMID- 11523937
TI  - Enteroaggregative Escherichia coli infection in a rabbit model.
AB  - Type strains of enteroaggregative Escherichia coli EAEC (17-2, serotype O3:H2; JM
      221, serotype O92:H33), isolates from an adult and a child with diarrhoea and an
      asymptomatic colonised child were used to orally infect adult rabbits. The
      experimental animals were followed up and sacrificed at defined time periods.
      Colonisation of both small and large intestine was seen with all strains and
      isolates used. Isolates from an adult patient with diarrhoea (MP 27) and from an
      asymptomatic colonised child from the community (KM 1337) were recovered from the
      small intestine during the first week of infection and subsequently from the
      large intestine. A total of seven rabbits was infected with MP 27; while
      colonising the gastrointestinal tract of all seven rabbits, this isolate caused
      diarrhoea in only one. On ultrastructural examination, the rabbits infected with
      17-2 showed invasion of lymphoid follicles. Bacteria were seen in intercellular
      spaces and within M cells, a finding that has not previously been described. It
      is clearly possible to produce gut colonisation by oral infection with EAEC in
      adult rabbits with normal flora.

PMID- 11523938
TI  - A comparison of the sensitivity of APTT reagents to the effects of enoxaparin, a
      low-molecular weight heparin.
AB  - Low-molecular weight heparin (LMWH) is the product of enzymatic or chemical
      degradation of unfractionated heparin (UFH). It has been found to have better bio
      availibility, more predictable dose response and can be used as an alternative to
      UFH for prophylaxis and treatment of thrombotic disorders. It is claimed that no
      laboratory monitoring is necessary for LMWH therapy; however, for the aged, renal
      impaired, obese or grossly underweight, monitoring of dose effect with anti-Xa
      assay is recommended. The activated partial thromboplastin time (APTT), which is
      the test of choice for UFH monitoring, is believed to be insensitive to the
      effect of LMWH. The sensitivity of the APTT to heparin lies in the APTT reagent
      used. In this study, eight different APTT reagents were used to compare the APTT
      with anti-Xa activity in ex vivo plasma from patients who were on enoxaparin
      (LMWH, Clexane) therapy. It was found that, as with UFH, APTT reagents show
      variable sensitivity to LMWH. The APTTs from all eight reagents were found to
      have a linear relationship to anti-Xa activity. The APTT results using three of
      the reagents gave an indication of the use of LMWH therapy. It was also found
      that patients who were lupus anticoagulant (LA)-positive had much more prolonged
      APTTs when on LMWH therapy; however, a linear correlation between APTT and anti
      Xa was not present in these patients.

PMID- 11523939
TI  - Diagnosis of enteric pathogens in children with gastroenteritis.
AB  - The aim of this study was to determine the isolation trends of common and
      emerging pathogens in children over a 12-month period. The study group included
      412 children under 6 years with diarrhoea who were either hospitalised, or seen
      in the outpatients department of The Sydney Children's Hospital. Pathogens were
      detected in 137 (33%) samples, with rotavirus most common (40%), followed by
      adenovirus (26%), astrovirus (12%), Campylobacter jejuni (12%), Salmonella spp.
      (10%) and Giardia lamblia (< 1 %). Giardia-specific antigen (GSA) was detected in
      11 of 382 (3%) using an enzyme immunoassay (EIA), and this included four samples
      in which cysts of G. lamblia were detected by microscopy. Using electron
      microscopy (EM), viruses were detected in 29 of 120 (24%) samples from
      hospitalised children and 53 of 171 (31%) outpatients (P = 0.23). Amongst this
      subset, Norwalk-like viruses (NLVs) were detected by RT-PCR in 10 samples
      including six of 14 with small round viruses, one of seven with small viral-like
      particles (SVLPs), and three of 126 EM-negative samples. Lactoferrin, detected by
      EIA, was 59% more likely to be positive in samples infected with
      salmonella/campylobacter than in samples in which bacterial pathogens were not
      isolated. As an indicator for infection with these bacterial agents, the assay
      showed a sensitivity and specificity of 95 and 40.3%, respectively. A routine
      microbiological analysis of stools from children of this age group should include
      a screen for foodborne bacterial agents and rotavirus. Tests for adenovirus,
      astrovirus and NLVs should be secondary. The cost-effectiveness of including the
      EIAs for lactoferrin and G. lamblia in the routine testing protocol needs to be
      evaluated.

PMID- 11523940
TI  - Surveillance of antibiotic resistance in invasive isolates of Neisseria
      meningitidis in Australia 1994-1999.
AB  - A total of 1434 strains of Neisseria meningitidis isolated from cases of invasive
      meningococcal disease (IMD) in Australia between 1994 and 1999 were examined by
      standard methods for susceptibility to antibiotics used for treatment and
      prophylaxis. The proportion of isolates fully susceptible to penicillin decreased
      from 45% in 1994 to 26% in 1999 (P<0.001). All the other isolates were less
      sensitive to penicillin except for two meningococci with a penicillin MIC of 1
      mg/l. The geometric mean penicillin MIC increased from 0.045 to 0.065 mg/l from
      1994 to 1999. There was no significant difference in the geometric mean
      penicillin MICs of serogroup B and serogroup C meningococci. Penicillin
      susceptibility was significantly associated with a poorer outcome. Isolates from
      survivors of IMD had a higher geometric mean penicillin MIC (0.06 mg/l) than
      those from fatal cases (0.048 mg/l) (P< 0.001). This suggests that factors other
      than the decrease in susceptibility to penicillin observed were more relevant to
      outcome in IMD. All isolates were fully susceptible to ceftriaxone. Rifampicin
      resistance was infrequent (eight isolates in 6 years) and sporadic. A single
      isolate had decreased quinolone susceptibility. Despite the significant shift in
      susceptibility to penicillin recorded, this group of antibiotics remains a
      suitable treatment for IMD in Australia.

PMID- 11523941
TI  - Isolation of Helicobacter pylori after transport from a regional laboratory of
      gastric biopsy specimens in saline, Portagerm pylori or cultured on chocolate
      agar.
AB  - Multiple gastric biopsies were taken from 288 patients in Port Lincoln, South
      Australia. One biopsy was used for a CLOtest and the other three were transported
      to a central laboratory in Adelaide in physiological saline, Portagerm pylori
      transport medium or after culture on a chocolate agar plate which was placed in a
      Biobag. Helicobacter pylori was isolated from 18.3% of patients. There was a
      95.7% concordance between culture results and the CLOtest result. Recovery rates
      after transport on chocolate agar, Portagerm pylori and in saline were 90.2, 90.2
      and 84.3%, respectively.

PMID- 11523942
TI  - Proteome analysis of Helicobacter pylori: major proteins of type strain NCTC
      11637.
AB  - Proteome analysis involves the simultaneous resolution and display of proteins
      produced by an organism, followed by the quantitation, characterisation and
      identification of these proteins. As part of an ongoing study mapping and
      comparing the proteins expressed by various strains of the pathogenic bacterium
      Helicobacter pylori, we have resolved and identified 93 of the most abundant
      proteins expressed by type reference strain NCTC 11637. Proteins were separated
      by two-dimensional gel electrophoresis and stained with Coomassie G250. Intensely
      stained spots were excised and digested with trypsin, and the resulting peptides
      were characterised by mass spectrometry. Proteins were then identified by
      correlating actual peptide profiles with theoretical profiles generated from
      published nucleotide sequences. Ninety-three of the most intensely-stained
      protein spots were identified as the products of 35 genes, giving a ratio of 2.7
      protein gene-products per gene. The products of the tsaA, pfr, ureA and ureB
      genes were amongst several proteins present in multiple isoforms. Peptide mass
      fingerprinting data were used to identify probable post-translational protein
      modifications. These results suggest that H. pylori proteins are subject to a
      high degree of post-translational modification. Comparative proteomics of H.
      pylori strains should greatly assist in investigating the pathogenic properties
      of this bacterium.

PMID- 11523943
TI  - Confirmation of invasive meningococcal disease by single point estimation of IgM
      antibody to outer membrane protein of Neisseria meningitidis.
AB  - OBJECTIVES: The sensitivity of laboratory confirmation of invasive meningococcal
      disease (IMD) by culture or PCR is affected by prior antibiotic treatment and
      decreasing use of early lumbar puncture. Serological diagnosis of IMD is not
      widely used because of reliance on paired serum samples. The application of
      single point estimations of IgM antibodies in the diagnosis of IMD was explored.
      DESIGN: Outer membrane proteins from a mix of commonly encountered meningococcal
      serotypes were partially purified and used as an antigen in an enzyme immunoassay
      for the detection of IgM antibody. The cut-off for the assay was derived using
      sera from blood bank donors and the accuracy then evaluated with sera from
      patients with culture-confirmed IMD, other bacterial infections and culture
      proven nasopharyngeal colonisation with Neisseria meningitidis. RESULTS: The
      coefficient of variability of the assay was < 10% in negative, mid- and high
      range positive sera and the specificity of the assay was at least 93%. In sera
      collected from 49 adult patients at various times after positive blood or CSF
      culture-confirmed IMD, the assay had a sensitivity of 100% in specimens collected
      between 5 and 18 days. At the time of isolation of meningococci from either blood
      or CSF, eight of 29 sera were IgM-positive, but beyond 70 days no positive
      results were detected. No differences were seen in the IgM responses in patients
      from whom different serogroups of N. meningitidis were recovered. CONCLUSIONS:
      Serological examination by single point IgM enzyme immunoassay (EIA) offers the
      possibility of an expanded laboratory confirmation of IMD in adults for samples
      taken between 5 and 18 days after onset.

PMID- 11523944
TI  - Test and teach. Laboratory characterisation of paraproteins. Heavy chain disease.

PMID- 11523945
TI  - Test and teach. Is it cancer? Renal tubular epithelial dysplasia.

PMID- 11523946
TI  - Spinal chloroma presenting with triplegia in an aleukaemic patient.
AB  - Malignant myeloid blast cells may occasionally form a solid mass in tissues
      outside the haemopoietic system. These tumours are known as chloromas or
      granulocytic sarcomas. Chloromas occur most commonly in the context of acute
      myelogenous leukaemia but, rarely, they occur in the absence of other
      haematological disease, and may be misdiagnosed as lymphoma. A case of a
      previously well 35-year-old woman presenting with rapidly progressive triplegia
      caused by a paraspinal and extradural cervical chloroma with no evidence of bone
      marrow or other haematological involvement is described. Few cases of spinal cord
      compression caused by chloroma in otherwise healthy patients have been reported.
      Morphological features of myeloid differentiation, histochemistry and
      immunohistochemistry, may all aid in rapid diagnosis and allow early and
      appropriate therapy.

PMID- 11523948
TI  - Focal nodular hyperplasia with calcification and ossification.
AB  - We describe a 33-year-old woman with Crohn's disease, who presented with
      recurrent episodes of small bowel obstruction. A solitary liver lesion was
      discovered incidentally by abdominal ultrasound. Pathological examination of the
      resected specimen revealed features typical of focal nodular hyperplasia together
      with uncommon findings including calcification, ossification and fibrous
      obliteration of blood-filled "cysts", changes more commonly associated with
      regression in hepatic haemangiomas. This report strengthens the favoured
      hypothesis that a vascular malformation underlies the pathogenesis of focal
      nodular hyperplasia.

PMID- 11523947
TI  - Multiple small intestinal stromal tumours in a patient with previously
      unrecognised neurofibromatosis type 1: immunohistochemical and ultrastructural
      evaluation.
AB  - Neurofibromatosis type 1 could be associated with multiple gastrointestinal
      stromal tumours, although their presence is not considered among the major
      diagnostic criteria. We present here a case of a 50-year-old female complaining
      of abdominal pain, with about 100 small intestinal stromal tumours. This finding
      prompted us to suspect a neurofibromatosis which was clinically confirmed
      afterwards. Light microscopy examination revealed a low-grade stromal tumour with
      skeinoid fibres. Mixed neural-interstitial cells of Cajal origin or,
      alternatively, neural differentiation of interstitial cells of Cajal are
      discussed on the basis of immunophenotype (CD117+, CD34+) and ultrastructure. A 2
      year follow-up did not indicate an aggressive course in the case of this
      neoplasm.

PMID- 11523949
TI  - Cystadenoma of the seminal vesicle: report of a case with ultrastructural
      findings.
AB  - Cystadenomas of the seminal vesicles are extremely rare benign tumours. We have
      not been able to find more than 10 cases in the literature. A benign cystadenoma
      of the seminal vesicle is described in a 49-year-old man. The clinical
      presentation, gross appearance, microscopic characteristics, immunohistochemical
      and ultrastructural findings of this uncommon tumour are discussed. The purpose
      of this paper is to report an unusual case of cystadenoma of the seminal vesicle
      and review the 10 previously reported cases in the English literature.

PMID- 11523950
TI  - Tissue factor assays: correlation with current prognostic tumour markers.

PMID- 11523951
TI  - A review of the nature and treatment of sleep disorders in individuals with
      developmental disabilities.
AB  - This paper describes research on the prevalence, correlates, and treatment of
      sleep disorders in individuals with developmental disabilities. A significant
      number of individuals with developmental disabilities have disordered sleep,
      although prevalence estimates vary from 13% to 86%. Constitutional variables,
      including age, presence of physical and sensory impairments, and certain genetic
      syndromes and medical conditions appear to be related to sleep disturbance, but
      the evidence is mainly correlational and therefore cannot be said to show a
      causal relation. While a number of behavioral interventions have proven effective
      in the treatment of sleep disturbance, and drug therapy involving melatonin
      appears promising, epidemiologic work on the correlates of sleep disorders appear
      to have had little impact on treatment. Consideration of the nature of sleep
      disorders may enhance treatments for individuals with developmental disabilities.

PMID- 11523952
TI  - The adaptive behavior scale-residential and community (part I): towards the
      development of a short form.
AB  - A potential 24-item short form (SABS) of the 73-item Adaptive Behavior Scale
      Residential and Community (Part I) (ABS-RC2; Nihira et al., 1993a, b) was
      developed, based on data from two diverse UK samples of adults with intellectual
      disabilities living in residential services (n = 560 and 254). SABS factor and
      total scores showed good internal reliability in both samples (alpha 0.89-0.98),
      and were highly correlated with their full ABS-RC2 Part I equivalents (r = 0.97
      0.99). Regression equations were calculated for SABS factor and total scores
      against their full ABS-RC2 Part I equivalents. Levels of agreement between
      predicted quartile scores (derived from the regression equations) and actual full
      ABS-RC2 Part I quartile scores were high (kappa 0.75-0.89; percentage agreement
      82%-92%). It is concluded that the SABS is a potentially useful research tool,
      although further work is clearly needed to establish the reliability and cross
      cultural validity of the instrument.

PMID- 11523953
TI  - The UCLA reading and writing program: an evaluation of the beginning stages.
AB  - Some individuals with developmental disabilities fail to acquire functional
      speech despite extensive teaching efforts. To help such individuals develop
      functional communication skills, a "reading and writing" program was developed.
      This study was designed to evaluate early parts of the program. Acquisition,
      transfer, and maintenance of "reading and writing" skills was examined and
      compared with the acquisition, transfer, and maintenance of sign language.
      Participants were four children with autism, who scored within the mentally
      retarded range on standardized tests of intellectual, adaptive, and language
      functioning, and three 3-year-old non-disabled children. A simultaneous-treatment
      design was employed to compare the rate of acquisition of "reading and writing"
      skills to the rate at which the participants acquired receptive and expressive
      signs. For the participants with autism, acquisition of "reading and writing" was
      more successful than receptive and expressive signing on all variables assessed.
      All non-disabled participants acquired all of the "reading and writing" and sign
      language skills, but participants with autism did not. However, "reading" was
      acquired slightly quicker by the participants with autism than the non-disabled
      participants, and the participants with autism also showed some evidence of
      better transfer and maintenance than the non-disabled participants did.

PMID- 11523954
TI  - Using multiple microswitches to promote different responses in children with
      multiple disabilities.
AB  - We examined the use of multiple microswitches to enhance different responses and
      environmental control with two boys with multiple disabilities. Four and three
      microswitches were used for the two boys, respectively. The microswitches were
      introduced individually. Once responding was established, two or three
      microswitches would be simultaneously available to allow the boys a wider range
      of response opportunities and a greater, more differentiated environmental input.
      Data showed that both boys learned to respond to the individual microswitches.
      The simultaneous availability of two or three microswitches promoted high levels
      of cumulative responding. Implications of the findings are discussed.

PMID- 11523955
TI  - Teaching students to self-regulate their behavior: the differential effects of
      student-vs. teacher-delivered reinforcement.
AB  - The effects of selected student-directed learning strategies on the classroom
      behavior of six students with varying disabilities in general education were
      examined using a multiple baseline design across groups. Target behaviors
      included academic, study, and social skills. Results indicated increases in
      student target performance for all participants, however, differential effects
      were observed across groups and reinforcement conditions (student-vs. teacher
      delivered). Additionally, anecdotal reports obtained from the cooperating teacher
      and students supported the study's findings. The implications of these findings
      are discussed.

PMID- 11523957
TI  - The enactment of national health insurance: a Boolean analysis of twenty advanced
      industrial countries.
AB  - The scholarly literature on health care politics has generated a series of
      hypotheses to explain U.S. exceptionalism in health policy and to explain the
      adoption of national health insurance (NHI) more generally. Various cultural,
      institutional, and political conditions are held to make the establishment of
      some form of national health insurance policy more (or less) likely to occur. The
      literature is dominated by national and comparative case studies that illustrate
      the theoretical logic of these hypotheses but do not provide a framework for
      examining the hypotheses cross-nationally. This article is an initial attempt to
      address that void by using Boolean analysis to examine systematically several of
      the major propositions that emerge from the case study literature on the larger
      universe of twenty advanced industrial democracies. This comparative analysis
      offers considerable support for the veto points hypothesis while still finding
      each of the factors examined to be relevant in certain scenarios. We conclude
      with a discussion of the implications of these findings for future research and
      for advocates of national health insurance in the United States.

PMID- 11523958
TI  - Medical savings accounts in Singapore: a critical inquiry.
AB  - With the United States currently experimenting with medical savings accounts
      (MSAs), it is appropriate to revisit the Singapore experience, where the practice
      has been in place for a decade and half. Singapore runs a modern, effective
      health system at a fraction of the cost of most systems operating in the
      developed West. Although MSAs contribute to the framework of a cultural rhetoric
      of personal responsibility for health care, this article argues that the heart of
      the Singapore system of health funding, with its financial discipline, is
      government control of inputs and outputs and strict rationing of health services
      according to wealth.

PMID- 11523959
TI  - Medical savings accounts in Singapore: what can we know?

PMID- 11523960
TI  - Behind the ideology and theory: what is the empirical evidence for medical
      savings accounts?

PMID- 11523961
TI  - Values and health policy: the case of Singapore.

PMID- 11523962
TI  - The impact of South Africa's new constitution on the organization of health
      services in the post-apartheid era.
AB  - This essay evaluates the transformation of the health care system in South Africa
      in the five years following the end of apartheid. This period has witnessed
      dramatic and wide-ranging changes in the roles of the central and provincial
      governments as well as many of the same problems related to decentralization as
      have been seen elsewhere in the world. The importance of effective
      intergovernmental relations to the creation of a national health system is
      highlighted. Negotiation. contracting, and coordination skills and mechanisms
      need to be strengthened to ensure a more effective national health system within
      a decentralized political system.

PMID- 11523964
TI  - Auto hypocrisy.

PMID- 11523963
TI  - Pegram v. Herdrich: On peritonitis, preemption, and the elusive goal of managed
      care accountability.
AB  - Managed care presents the paradox of organizations having real power over
      people's lives without there being clear or consistent means of ensuring
      accountability. In Pegram v. Herdrich, the United States Supreme Court struggled
      with whether "fiduciary duties" under the federal Employee Retirement Income
      Security Act (ERISA) could be used to counterbalance the incentives that HMOs
      have to deny necessary care. Given press coverage of the case, however, it was
      easy to get the impression that the managed care industry itself was on trial in
      Pegram. This report examines the political and legal forces underlying the
      dispute and analyzes the Supreme Court's unanimous rejection of the notion of
      federally imposed duties for HMOs. In the absence of ERISA fiduciary obligations,
      attention must now shift to developments in state tort law, the scope of federal
      ERISA preemption, and the prospect of legislative reform. The report concludes
      with an exploration of how the elusive goal of managed care accountability might
      be pursued in the wake of Pegram.

PMID- 11523965
TI  - Role of agitation in prediction of outcomes after traumatic brain injury.
AB  - OBJECTIVE: To determine the role of agitation in the prediction of traumatic
      brain injury rehabilitation outcomes. DESIGN: A longitudinal study of 340
      consecutive patients admitted to an acute traumatic brain injury rehabilitation
      unit was conducted. Outcomes under study included rehabilitation length of stay,
      discharge destination, functional independence at discharge (FIM instrument),
      productivity at 1-yr follow-up, and life satisfaction at 1-yr follow-up
      (Satisfaction with Life Scale). RESULTS: Univariate analyses suggested that the
      presence of agitation in rehabilitation is predictive of a longer length of stay
      and decreased functional independence in the cognitive realm at discharge. In
      addition, individuals who exhibit agitation at any time during rehabilitation are
      less likely to be discharged to a private residence. However, multivariate
      analyses indicated that cognitive functioning at admission to rehabilitation (FIM
      cognitive) mediates the relationship between the presence of agitation and length
      of rehabilitation, as well as between agitation and FIM cognitive at discharge.
      Similar results were found when discharge residence was the dependent variable;
      however, agitation also contributed some unique variance to the prediction. Lower
      cognitive functioning at admission to rehabilitation was associated with the
      occurrence of agitation during rehabilitation, longer length of stay, lower
      cognitive functioning at discharge, and a decreased likelihood that an individual
      would be discharged to a private residence. CONCLUSIONS: The results of the
      multivariate analyses support the contention that agitation and cognition are
      intimately related, with the long-term effects of the former being at least
      partially driven by the latter. These findings support the importance of
      systematically monitoring both agitation and cognition when applying
      interventions to reduce agitation.

PMID- 11523966
TI  - Predicting outcomes of patients in Japan after first acute stroke using a simple
      model.
AB  - OBJECTIVE: Prediction of patient outcome can be useful as an aid to clinical
      decision making. Many studies, including my own, have constructed predictive
      multivariate models for outcome following stroke rehabilitation therapy, but
      these have often required several minutes work with a pocket calculator. The aim
      is to develop a simple, easy-to-use model that has strong predictive power.
      METHODS: Four hundred sixty-four consecutive patients with first stroke who were
      admitted to a rehabilitation hospital during a period of 19 mo were enrolled in
      the study. Sex, age, the stroke type, Functional Independence Measure total score
      on admission (X), onset to admission interval (number of days from stroke onset
      to rehabilitation admission), and length of rehabilitation hospital stay (number
      of days from hospital admission to discharge) were the independent variables.
      Functional Independence Measure total score at discharge (Y) was the dependent
      variable. RESULTS: Stepwise multiple regression analysis resulted in the model
      containing age (P < 0.0001), X (P < 0.0001), and onset to admission interval (P <
      0.0001). The equation was: Y = 68.6 - 0.32 (age) + 0.80X - 0.13 (onset to
      admission interval), a multiple correlation coefficient (R) = 0.82, and a
      multiple correlation coefficient squared (R2) = 0.68. Simple regression analysis
      revealed the relation between Xand Y: Y = 0.85X + 37.36, and R = 0.80 R2 = 0.64.
      In fact, plots of X vs. Ywere nonlinear, but seemed to be able to be linearized
      by some form of equation. It was found that there is a linear relation between
      logX and Y. The equation is Y = 106.88x - 95.35, where x = logX, R = 0.84, and R2
      = 0.70. The correlation is improved by a regression analysis of a natural
      logarithmic transformation of X (R = 0.84 vs. R = 0.82). CONCLUSION: The results
      in this study confirm that the simple regression model using a logarithmic
      transformation of X (R = 0.84) has predictive power over the simple regression
      model (R = 0.80). This model is well validated and clinically useful.

PMID- 11523967
TI  - Isokinetic measurement of trunk muscle strength in women with chronic low-back
      pain.
AB  - OBJECTIVES: To investigate the relationships among chronic low-back pain and
      obesity, total spinal range of motion, and trunk muscle strength. The short-term
      impact of trunk muscle strengthening exercises on this condition was also
      examined. DESIGN: A controlled, prospective study of trunk muscle strengths of
      patients with chronic low-back pain and the short-term impact of exercise on
      strength. The study group consisted of 25 female patients who had been
      experiencing low-back pain for at least 3 mo, and the control group included 20
      age-matched women without known low-back trouble. The Davenport Index was used to
      calculate the body mass indexes of all subjects. The Oswestry Disability
      Questionnaire was used to assess pain in the study group. Full flexion and
      extension ranges of motion were measured, then isokinetic measurements of trunk
      muscles were performed at 60-, 120-, and 180-degrees/sec velocities. Isometric
      measurements were also recorded for both flexors and extensors at a 60-degree
      angle. RESULTS: Increased body mass index and decreased trunk muscle strength
      were found to be directly associated with chronic low-back pain (P < 0.05). After
      a 15-day standard trunk strengthening exercise program in the patient group,
      trunk muscle strength was found to be increased (P < 0.05). CONCLUSIONS: Obesity
      and decrease in trunk muscle strength are important factors in chronic low-back
      pain, and a trunk muscle strengthening program will be helpful in reducing the
      pain.

PMID- 11523968
TI  - Intersection syndrome in Buriram Hospital: a 4-yr prospective study.
AB  - OBJECTIVE: To determine the prevalence, demographic characteristics, symptoms,
      treatment, and outcome of patients who presented to Buriram Provincial hospital
      and were diagnosed with intersection syndrome. DESIGN: This was a 4-yr
      prospective study that included all patients with new complaints of forearm and
      hand pain who presented to Buriram hospital as inpatients or outpatients.
      RESULTS: The prevalence of intersection syndrome was found to be 0.37% of all
      patients (8080) with arm or hand pain. Of the 30 patients presenting with
      intersection syndrome, all had forearm pain, 22 (73.3%) had swelling, and 12
      (40%) had crepitus noted in the intersected region. Fourteen (46.7%) patients
      reported pain provoked with twisting hand motions with radial deviations, 4
      (13.3%) with pulling, and 12 (40%) with combinations of multiple hand movements
      (threshing, planting, hammering, hand washing, spraying and cementing). The
      majority of the patients were male (70%) farmers (60%). Twenty-nine patients
      received nonoperative treatment, including modified work activities to reduce
      stress on the wrist, nonsteroidal anti-inflammatory, and analgesic medications.
      One patient received only analgesic medication. One patient additionally required
      a resting hand splint. Every patient was seen for follow-up within the next 7
      days. By 12-18 months posttreatment, there were only 14 patients (46.6%)
      remaining in follow-up, none with any symptom recurrence. CONCLUSION:
      Intersection syndrome is a relatively uncommon, overused syndrome that is
      associated with repeated radial deviation of the wrist and responds favorably to
      conservative treatment.

PMID- 11523969
TI  - Developing meaningful Fear of Falling Measures for community dwelling elderly.
AB  - OBJECTIVE: The objective of this study is to demonstrate how a Rasch analytic
      approach can be used to create fear of falling measures that remain connected to
      the meaningful descriptions provided by the instrument items. DESIGN: The
      University of Illinois at Chicago Fear of Falling Measure was developed using
      focus groups and consists of 19 common activities designed to represent an
      increasing level of concern about falling among older adults. RESULTS: Rasch
      analysis of responses from 106 community dwelling elderly revealed that the two
      middle rating scale categories (a little worried and moderately worried) were not
      being used in the expected fashion. After modification of the rating scale, Rasch
      analysis showed that the three items causing the least worry (get dressed, get
      on/off toilet, and get in/out of bed) were statistically erratic. CONCLUSION:
      Final analysis demonstrated that the remaining 16 items represented a
      unidimensional construct that, in general, supported the original expected item
      difficulty hierarchy. Because person and item measures were calibrated on the
      same linear scale person measures are translatable to item descriptions. This
      connection provides meaning to the numeric values obtained from the instrument
      and provides a basis for setting clinically relevant criteria for interventions.

PMID- 11523970
TI  - Relationship between self-reported disability and caregiver hours.
AB  - OBJECTIVE: In a large, population-based cohort of patients with spinal cord
      dysfunction, we assessed the relationship between self-reported physical function
      and hours of care received. DESIGN: Data were obtained by a cross-sectional, self
      administered survey used to help establish a national registry of veterans with
      spinal cord dysfunction. Participants were originally identified from Department
      of Veterans Affairs databases as having a high probability of spinal cord
      dysfunction. All 13,542 respondents reporting spinal cord dysfunction and also
      having complete data on physical function and caregiver hours (CGHs) were
      included. Physical function was measured using the Self-Reported Functional
      Measure, and CGHs were obtained from a self-report of hours of caregiving
      received during the last 2 wk. RESULTS: The relationship between self-reported
      disability and CGHs was strong (Spearman correlation = -0.70). Subjects with
      moderate levels of disability had the most variability in CGHs. After stratifying
      by total Self-Reported Functional Measure score, the strongest predictors of CGHs
      were instrumental activities of daily living and individual Self-Reported
      Functional Measure items, explaining a moderate amount of variation in CGHs.
      CONCLUSION: These data support the construct validity of the Self-Reported
      Functional Measure and suggest that self-reported disability measures can be of
      use in describing the clinical epidemiology of patients with spinal cord
      dysfunction.

PMID- 11523971
TI  - Manual and oral apraxia in acute stroke, frequency and influence on functional
      outcome: The Copenhagen Stroke Study.
AB  - OBJECTIVES: To determine the frequency of manual and oral apraxia in acute stroke
      and to examine the influence of these symptoms on functional outcome. DESIGN:
      Seven hundred seventy six unselected, acute stroke patients who were admitted
      within seven days of stroke onset with unimpaired consciousness were included. If
      possible, the patients were assessed for manual and oral apraxia on acute
      admission. Neurologic stroke severity including aphasia was assessed with the
      Scandinavian Stroke Scale, and activities of daily living function was assessed
      with the Barthel Index. All patients completed their rehabilitation in the same
      large stroke unit. RESULTS: Six hundred eighteen patients could cooperate with
      the apraxia assessments. Manual apraxia was found in 7% of subjects (10% in left
      and 4% in right hemispheric stroke; chi2 = 9.0; P = 0.003). Oral apraxia was
      found in 6% (9% in left and 4% in right hemispheric stroke; chi2 = 5.4; P =
      0.02). Both manual and oral apraxia were related to increasing stroke severity,
      and manual, but not oral, apraxia was associated with increasing age. There was
      no gender difference in frequency of apraxia. Patients with either type of
      apraxia had temporal lobe involvement more often than patients without. When
      analyzed with multiple linear and logistic regression analyses, neither manual
      nor oral apraxia had any independent influence on functional outcome. CONCLUSION:
      Apraxia is significantly less frequent in unselected patients with acute stroke
      than has previously been assumed and has no independent negative influence on
      functional outcome.

PMID- 11523972
TI  - Nontraumatic vs. traumatic spinal cord injury: a rehabilitation outcome
      comparison.
AB  - OBJECTIVE: Nontraumatic spinal cord injury (SCI) represents a significant
      proportion of individuals admitted for SCI rehabilitation; however, there is
      limited literature regarding their outcomes. As our society continues to age and
      nontraumatic injuries present with greater frequency, further studies in this
      area will become increasingly relevant. The objective of this study was to
      compare outcomes of patients with nontraumatic SCI with those with traumatic SCI
      after inpatient rehabilitation. DESIGN: A longitudinal study with matched block
      design was used comparing 86 patients with nontraumatic SCI admitted to a SCI
      rehabilitation unit and 86 patients with traumatic SCI admitted to regional model
      SCI centers, controlling for age, neurologic level of injury, and American Spinal
      Injury Association impairment classification. Main outcome measures included
      acute and rehabilitation hospital length of stay, FIM scores, FIM change, FIM
      efficiency, rehabilitation charges, and discharge-to-home rates. RESULTS: Results
      indicate that when compared with traumatic SCI, patients with nontraumatic SCI
      had a significantly (P < 0.01) shorter rehabilitation length of stay (22.38 vs.
      41.35 days) and lower discharge FIM scores (57.3 vs. 65.6), FIM change (18.6 vs.
      31.0), and rehabilitation charges ($25,050 vs. $64,570). No statistical
      differences were found in acute care length of stay, admission FIM scores, FIM
      efficiency, and community discharge rates. CONCLUSIONS: The findings indicate
      that patients with nontraumatic SCI can achieve rates of functional gains and
      community discharge comparable with traumatic SCI. Whereas patients with
      traumatic SCI achieved greater overall functional improvement, patients with
      nontraumatic SCI had shorter rehabilitation length of stay and lower
      rehabilitation charges. These findings have important implications for the
      interdisciplinary rehabilitation process in the overall management and outcome of
      individuals with nontraumatic SCI.

PMID- 11523973
TI  - Meralgia paresthetica as the presenting feature of chronic appendicitis.
AB  - Meralgia paresthetica is an entrapment syndrome of the lateral cutaneous nerve of
      the thigh manifesting as paresthesia, pain, numbness, or sensory loss in the
      distribution of the nerve. A variety of causes have been described; however, the
      etiology often remains unknown. On the basis of our investigations with a patient
      with meralgia paresthetica, we determined that an inflammatory rather than
      mechanical effect on the lateral cutaneous nerve of the thigh may account for the
      pathogenesis; however, a certain conclusion about this issue can not be made.

PMID- 11523975
TI  - Multicenter clinical trials to establish the benefit of early intervention in
      spinal cord injury.

PMID- 11523974
TI  - Resident research education in physical medicine and rehabilitation: a practical
      approach.
AB  - The Accreditation Council for Graduate Medical Education includes training in
      research as a required component of physical medicine and rehabilitation
      residency programs. Unfortunately, there is a lack of practical information on
      how to meet this requirement. In this paper, information is provided for
      individuals involved in resident education on how to teach residents about
      research.

PMID- 11523976
TI  - The influence of the surface treatment and saliva on the color of two porcelains.
AB  - The color of an object is a psychophysical phenomenon. Regarding its physical
      aspect, the amount of light reflected from the surface of an object is taken into
      consideration many times. Two brands of porcelain were used to make 10 specimens
      that were submitted to the following treatments: glaze, grinding, polishing and
      overglaze. All samples were analyzed with or without saliva. The final color
      differences of the ceramic were evaluated using a spectrophotometer, and
      reflectance curves were obtained. Results showed that there were no differences
      between the brands of porcelain. Saliva did not interfere with the color of the
      porcelain, but re-established the original one, after the grinding process had
      altered it. The polishing also contributed to re-established the original color.
      The overglaze altered the original color, with or without saliva.

PMID- 11523977
TI  - Development of Ag-Pd-Au-Cu alloys for multiple dental applications. Part 2.
      Mechanical properties of experimental Ag-Pd-Au-Cu alloys containing Sn or Ga for
      ceramic-metal restorations.
AB  - Eighteen Ag-Pd-Au-Cu alloys, consisting of nine Ag-Pd-Au-Cu mother compositions
      (Pd: 20, 30 or 40%, Au: 20%, Cu: 10, 15 or 20%, Ag: balance) containing either 5%
      Sn or 5% Ga as an additive metal, were experimentally prepared. Tensile strength,
      proof stress, elongation, elastic modulus, and Vickers hardness of these alloys
      were evaluated to clarify the potential of these alloys for use as ceramic-metal
      restorations as well as the effects of the Pd and Cu contents on their mechanical
      properties. The tensile strength, proof stress, elongation, elastic modulus and
      Vickers hardness of the 18 experimental alloys were in the range of 410.0-984.0
      MPa, 289.7-774.3 MPa, 2.2-23.7%, 81.3-123.0 GPa and 135.7-332.3 HV1,
      respectively. Ten of the 18 experimental alloys can be used for ultra-low fusing
      ceramics based on their proof stress, elastic modulus, elongation and hardness.
      Between the Ga- and Sn-added alloys, differences in tensile strength, proof
      stress, elongation and hardness were found at several Ag-Pd-Au-Cu compositions.

PMID- 11523978
TI  - Application of electrolyzed acid water to sterilization of denture base part 1.
      Examination of sterilization effects on resin plate.
AB  - Bactericidal activities of electrolyzed strong and weak acid waters for acrylic
      denture base resin were evaluated in order to discuss the applicability of these
      waters for sterilization of denture base. Only 1-minute immersion in the
      electrolyzed strong or weak acid water could completely eliminate the attached
      bacteria, Staphylococcus aureus 209P, on the resin plate. When the resin was
      relined with tissue conditioner, 5-minute immersion or 1- to 2-minute ultrasonic
      cleaning reduced the number of the bacteria from 10(5)/cm2 level to 10(1)/cm2 and
      no surviving bacteria could be detected after 10-minute treatment. These findings
      suggest that both the electrolyzed strong and weak acid waters are well
      applicable to the disinfectant for acrylic denture base showing excellent
      bactericidal activities in a significantly shorter treatment as compared with the
      conventional denture cleaning.

PMID- 11523979
TI  - Cold crucible levitation melting of biomedical Ti-30 wt%Ta alloy.
AB  - Recently, titanium-tantalum alloys have been studied as implant materials for
      dental and orthopedic surgery. However, titanium and tantalum are difficult to
      mix by common arc melting and induction melting, because of their high melting
      point and the marked difference between their densities (Ti: 1,680 degrees C, 4.5
      g/cm3, Ta: 2,990 degrees C, 16.6 g/cm3). Thus, the Cold Crucible Levitation
      Melting (CCLM) method was chosen to produce a Ti-30 wt%Ta binary alloy in the
      present study. The CCLM furnace, with 1 kg capacity, consisted of a water-cooled
      crucible comprising oxygen-free high purity copper segments and coils wrapped
      around the crucible and connected to a frequency inverter power supply. A
      qualified ingot of 1.0 kg of Ti-30 wt%Ta alloy was obtained. The ingot was
      characterized from the surface quality, chemical composition distribution and
      microstructure, and finally the melting process was discussed.

PMID- 11523980
TI  - Clinical evaluation of an electron-ionizing toothbrush with a tooth paste
      containing stannous fluoride in treatment of dentine hypersensitivity following
      periodontal surgery.
AB  - The purpose of this study was to examine the effect of an electro-ionizing
      toothbrush with stannous fluoride in the treatment of dentin hypersensitivity
      following periodontal surgery. Thirty-two volunteers with dentin hypersensitivity
      were divided in two equal groups each using different methods: (Group I) stannous
      fluoride dentifrice and hyG Brnde ionizing brush without a battery and (Group II)
      stannous fluoride dentifrice and hyG Brnde ionizing brush with a battery. The
      volunteers brushed their teeth for 3 minutes twice a day for 12 weeks following
      one either of the test protocols. Mechanical (No 23 dental explorer), chemical
      (lemon juice) and thermal (dental air-water syringe) tests were used for the
      evaluation of the degree of dentin hypersensitivity. A subjective assessment of
      the degree of hypersensitivity for each stimulus was recorded. The evaluations
      were repeated at 4, 8 and 12 weeks after surgical treatment. The second group
      showed significantly less sensitivity than the first group. The findings appear
      to suggest that the ionizing brush may be an effective adjunct for the treatment
      of dentin hypersensitivity in post-periodontal surgery.

PMID- 11523981
TI  - Evaluation of the surface roughness of compomer by laser scanning microscopy.
AB  - The purpose of this study was to evaluate the effect of alcoholic and low pH soft
      drinks on the surface roughness of compomer restorative materials. There were
      five tested materials and four immersion media. Specimens were immersed in test
      solutions for a 10-day period at a temperature of 37 degrees C. Measurement of
      the surface texture was carried out using a laser scanning microscope (a non
      contact laser stylus tracing method). This was also used to produce the Laser
      Scanning Microscope Image (LSM Image). Specimens immersed in orange juice and
      whisky displayed higher values for Ra & Rz than specimens immersed in soft drinks
      and deionized water. LSM Image showed a difference between the control and the
      examined side, especially for specimens immersed in low pH soft drinks this could
      be due to the erosive effect of the media. Alcoholic and low pH soft drinks
      caused deterioration of the materials surface, which may lead to a clinically
      detectable rough and dull surface.

PMID- 11523982
TI  - A novel engineered subtilisin BPN' lacking a low-barrier hydrogen bond in the
      catalytic triad.
AB  - The low-barrier hydrogen bond (LBHB) between the Asp and His residues of the
      catalytic triad in a serine protease was perturbed via the D32C mutation in
      subtilisin BPN' (Bacillus protease N'). This mutant enzyme catalyzes the
      hydrolysis of N-Suc-Ala-Ala-Pro-Phe-SBzl with a k(cat)/K(m) value that is only 8
      fold reduced from that of the wild-type (WT) enzyme. The value of k(cat)/K(m) for
      the corresponding p-nitroanilide (pNA) substrate is only 50-fold lower than that
      of the WT enzyme (DeltaDeltaG++ = 2.2 kcal/mol). The pK(a) controlling the
      ascending limb of the pH versus k(cat)/K(m) profile is lowered from 7.01 (WT) to
      6.53 (D32C), implying that any hydrogen bond replacing that between Asp32 and
      His64 of the WT enzyme most likely involves the neutral thiol rather than the
      thiolate form of Cys32. It is shown by viscosity variation that the reaction of
      WT subtilisin with N-Suc-Ala-Ala-Pro-Phe-SBzl is 50% (sucrose) to 100% (glycerol)
      diffusion-controlled, while that of the D32C construct is 29% (sucrose) to 76%
      (glycerol) diffusion-controlled. The low-field NMR resonance of 18 ppm that has
      been assigned to a proton shared by Asp32 and His64, and is considered diagnostic
      of a LBHB in the WT enzyme, is not present in D32C subtilisin. Thus, the LBHB is
      not an inherent requirement for substantial rate enhancement for subtilisin.

PMID- 11523983
TI  - Characterization of the metal receptor sites in Escherichia coli Zur, an
      ultrasensitive zinc(II) metalloregulatory protein.
AB  - The Escherichia coli Zur protein is a Fur homologue that regulates expression of
      Zn(II) uptake systems. The zinc-loaded form of Zur is proposed to bind DNA and
      repress transcription of the znuABC genes. Recent in vitro data indicate that the
      transcriptional activity of Zur is half-maximal when free Zn(II) concentrations
      are in the sub-femtomolar range, making it the most sensitive Zn(II)
      metalloregulatory protein reported to date. Previous results indicate that Zur
      binds at least one zinc; however, little else is known about Zn(II) binding. We
      have purified E. coli Zur to homogeneity and found that it has two Zn(II) binding
      sites per monomer with different coordination environments. Using Zn(II) binding
      assays, ICP-AES analysis, and Zn EXAFS analysis, we show that one zinc is tightly
      bound in an S(3)(N/O) coordination environment. Both Co(II) and Zn(II) were
      substituted into the second metal binding site and probed by EXAFS and UV-visible
      absorption spectroscopy. These studies indicate that Co(II) is bound in an
      S(N/O)(3) coordination environment with tetrahedral geometry. The Zn(II) EXAFS of
      Zn(2)Zur, which is consistent with the results for both sites, indicates an
      average coordination environment of S(2)(N/O)(2), presumably due to one S(N/O)(3)
      site and one S(3)(N/O) site. These studies reveal the coordination environments
      that confer such exceptional zinc sensitivity and may provide the foundation for
      understanding the molecular basis of metal ion selectivity. A comparison of the
      metal binding sites in Zur with its Fe(II)-sensing homologue Fur provides clues
      as to why these two proteins with similar structures respond to two very
      different metal ions.

PMID- 11523984
TI  - The structure of lipoprotein(a) and ligand-induced conformational changes.
AB  - Lipoprotein(a) is composed of low-density lipoprotein linked both covalently and
      noncovalently to apolipoprotein(a). The structure of lipoprotein(a) and the
      interactions between low-density lipoprotein and apolipoprotein(a) were
      investigated by electron microscopy and correlated with analytical
      ultracentrifugation. Electron microscopy of rotary-shadowed and unidirectionally
      shadowed lipoprotein(a) prepared without glycerol revealed that it is a nearly
      spherical particle with no large projections. After extraction of both
      lipoprotein(a) and low-density lipoprotein with glycerol prior to rotary
      shadowing, the protein components were observed to consist of a ring of density
      made up of nodules of different sizes, with apolipoprotein(a) and apolipoprotein
      B-100 closely associated with each other. However, when lipoprotein(a) was
      treated with a lysine analogue, 6-aminohexanoic acid, much of the
      apolipoprotein(a) separated from the apolipoprotein B-100. In 6-aminohexanoic
      acid-treated preparations without glycerol extraction, lipoprotein(a) particles
      had an irregular mass of density around the core. In contrast, lipoprotein(a)
      particles treated with 6-aminohexanoic acid in the presence of glycerol had a
      long tail, in which individual kringles could be distinguished, extending from
      the ring of apolipoprotein B-100. The length of the tail was dependent on the
      particular isoform of apolipoprotein(a). Dissociation of the noncovalent
      interactions between apolipoprotein(a) and low-density lipoprotein as a result of
      shear forces or changes in the microenvironment may contribute to selective
      retention of lipoprotein(a) in the vasculature.

PMID- 11523985
TI  - Structures of heparin-derived disaccharide bound to cobra cardiotoxins: context
      dependent conformational change of heparin upon binding to the rigid core of the
      three-fingered toxin.
AB  - Glycosaminoglycans (GAGs) have been suggested to be a potential target for cobra
      cardiotoxin (CTX) with high affinity and specificity via a cationic belt at the
      concave surface of the polypeptide. The interaction of GAGs, such as high
      molecular weight heparin, with CTXs not only can induce aggregation of CTX
      molecules but also can enhance their penetration into membranes. The binding of
      short chain heparin, such as a heparin-derived disaccharide [DeltaUA2S(1-->4)
      alpha-D-GlcNS6S], to CTX A3 from Taiwan cobra (Naja atra), however, will not
      induce aggregation and was, therefore, investigated by high-resolution (1)H NMR.
      A novel heparin binding site on the convex side of the CTX, near the rigid
      disulfide bond-tightened core region of Cys38, was identified due to the
      observation of intermolecular NOEs between the protein and carbohydrate. The
      derived carbohydrate conformation using complete relaxation and conformational
      exchange matrix analysis (CORCEMA) of NOEs indicated that the glycosidic linkage
      conformation and the ring conformation of the unsaturated uronic acid in the
      bound state depended significantly on the charge context of CTX molecules near
      the binding site. Specifically, comparative binding studies of several heparin
      disaccharide homologues with two CTX homologues (CTX Tgamma from Naja nigricollis
      and CTX A3) indicated that the electrostatic interaction of N-sulfate of
      glucosamine with NH(3)(+)zeta of Lys12 and of the 2-O-sulfate of the unsaturated
      uronic acid with NH(3)(+)zeta of Lys5 played an important role. These results
      also suggest a model on how the CTX-heparin interaction may regulate heparin
      induced aggregation of the toxin via the second heparin binding site.

PMID- 11523986
TI  - A structural motif of acetylcholinesterase that promotes amyloid beta-peptide
      fibril formation.
AB  - Acetylcholinesterase (AChE) has been found to be associated with the core of
      senile plaques. We have shown that AChE interacts with the amyloid beta-peptide
      (Abeta) and promotes amyloid fibril formation by a hydrophobic environment close
      to the peripheral anionic binding site (PAS) of the enzyme. Here we present
      evidence for the structural motif of AChE involved in this interaction. First, we
      modeled the docking of Abeta onto the structure of Torpedo californica AChE, and
      identified four potential sites for AChE-Abeta complex formation. One of these,
      Site I, spans a major hydrophobic sequence exposed on the surface of AChE, which
      had been previously shown to interact with liposomes [Shin et al. (1996) Protein
      Sci. 5, 42-51]. Second, we examined several AChE-derived peptides and found that
      a synthetic 35-residue peptide corresponding to the above hydrophobic sequence
      was able to promote amyloid formation. We also studied the ability to promote
      amyloid formation of two synthetic 24-residue peptides derived from the sequence
      of a Omega-loop, which has been suggested as an AChE-Abeta interacting motif.
      Kinetic analyses indicate that only the 35-residue hydrophobic peptide mimics the
      effect of intact AChE on amyloid formation. Moreover, RP-HPLC analysis revealed
      that the 35-residue peptide was incorporated into the growing Abeta-fibrils.
      Finally, fluorescence binding studies showed that this peptide binds Abeta with a
      K(d) = 184 microM, independent of salt concentration, indicating that the
      interaction is primarily hydrophobic. Our results indicate that the homologous
      human AChE motif is capable of accelerating Abeta fibrillogenesis.

PMID- 11523987
TI  - Base sequence effects in bending induced by bulky carcinogen-DNA adducts:
      experimental and computational analysis.
AB  - The covalent binding of bulky mutagenic or carcinogenic compounds to DNA can lead
      to bending, which could significantly alter the interactions of DNA with critical
      replication and transcription proteins. The impact of adducts derived from the
      highly reactive bay region enantiomeric (+)- and (-)-anti-7,8-diol-9,10-epoxide
      derivatives of benzo[a]pyrene (BPDE) are of interest because the (+)-7R,8S,9S,10R
      anti-BPDE enantiomer is highly tumorigenic in rodents, while the (-)-7S,8R,9R,10S
      anti-BPDE enantiomer is not. Both (+)- and (-)-anti-BPDE bind covalently with DNA
      predominantly by trans addition at the exocyclic amino group of guanine to yield
      10S (+)- and 10R (-)-trans-anti-[BP]-N(2)-dG adducts. We have synthesized a
      number of different oligonucleotides with single (+)- and (-)-trans-anti-[BP]
      N(2)-dG adducts (G) in the base sequence context XG*Y, where X and Y are
      different DNA bases. The G* residues were positioned at or close to the center of
      11 base pair ( approximately 1 helical turn) or 16 base pair ( approximately 1.5
      turns) duplexes. All bases, except for X and Y and their partners, were
      identical. These sequences were self-ligated with T4 ligase to form multimers
      that yield a ladder of bands upon electrophoresis in native polyacrylamide gels.
      The extent of bending in each oligonucleotide was assessed by monitoring the
      decrease in gel mobilities of these linear, self-ligated oligomers, relative to
      unmodified oligonucleotides of the same base sequence. The extent of global
      bending was then estimated using a sequence-specific three-dimensional model from
      which the values of the base-pair step parameter roll adjacent to the lesion site
      could be extracted. We find that (+)-trans-anti-[BP]-N(2)-dG adducts are
      considerably more bent than the (-) isomers regardless of sequence and that A-T
      base pairs flanking the [BP]-N(2)-dG lesion site allow for local flexibility
      consistent with adduct conformational heterogeneity. Interestingly, the fit of
      computed versus observed gel mobilities using classical reptation treatments
      requires enhancement of unmodified DNA flexibility in gels, compared to aqueous
      salt solution. The differences in bending between the two stereoisomeric adduct
      duplexes and the observed base sequence context effects may play a significant
      role in the differential processing of these lesions by cellular replication,
      transcription, and repair enzymes.

PMID- 11523988
TI  - Solution structure of a guanine-N7-linked complex of the mitomycin C metabolite
      2,7-diaminomitosene and DNA. Basis of sequence selectivity.
AB  - 2,7-Diaminomitosene (2,7-DAM), the major metabolite of the antitumor antibiotic
      mitomycin C, forms DNA adducts in tumor cells. 2,7-DAM was reacted with the
      deoxyoligonucleotide d(GTGGTATACCAC) under reductive alkylation conditions. The
      resulting DNA adduct was characterized as d(G-T-G-[M]G-T-A-T-A-C-C-A-C) (5),
      where [M]G stands for a covalently modified guanine, linked at its N7-position to
      C10 of the mitosene. The adducted oligonucleotide complements with itself,
      retaining 2-fold symmetry in the 2:1 drug-duplex complex, and provides well
      resolved NMR spectra, amenable for structure determination. Adduction at the N7
      position of G4 ([M]G, 4) is characterized by a downfield shift of the G4(H8)
      proton and separate resonances for G4(NH(2)) protons. We assigned the
      exchangeable and nonexchangeable proton resonances of the mitosene and the
      deoxyoligonucleotide in adduct duplex 5 and identified intermolecular proton
      proton NOEs necessary for structural characterization. Molecular dynamics
      computations guided by 126 intramolecular and 48 intermolecular distance
      restraints were performed to define the solution structure of the 2,7-DAM-DNA
      complex 5. A total of 12 structures were computed which exhibited pairwise rmsd
      values in the 0.54-1.42 A range. The 2,7-DAM molecule is anchored in the major
      groove of DNA by its C10 covalently linked to G4(N7) and is oriented 3' to the
      adducted guanine. The presence of 2,7-DAM in the major groove does not alter the
      overall B-DNA helical structure. Alignment in the major groove is a novel feature
      of the complexation of 2,7-DAM with DNA; other known major groove alkylators such
      as aflatoxin, possessing aromatic structural elements, form intercalated
      complexes. Thermal stability properties of the 2,7-DAM-DNA complex 5 were
      characteristic of nonintercalating guanine-N7 alkylating agents. Marked sequence
      selectivity of the alkylation by 2,7-DAM was observed, using a series of
      oligonucleotides incorporating variations of the 5'-TGGN sequence as substrates.
      The selectivity correlated with the sequence specificity of the negative
      molecular electrostatic potential of the major groove, suggesting that the
      alkylation selectivity of 2,7-DAM is determined by sequence-specific variation of
      the reactivity of the DNA. The unusual, major groove-aligned structure of the
      adduct 5 may account for the low cytotoxicity of 2,7-DAM.

PMID- 11523989
TI  - Identification of amino acids in the tetratricopeptide repeat and C-terminal
      domains of protein phosphatase 5 involved in autoinhibition and lipid activation.
AB  - Protein phosphatase 5 (PP5) exhibits low basal activity due to the autoinhibitory
      properties of its N-terminal and C-terminal domains but can be activated
      approximately 40-fold in vitro by polyunsaturated fatty acids. To identify
      residues involved in regulating PP5 activity, we performed scanning mutagenesis
      of its N-terminal tetratricopeptide repeat (TPR) domain and deletion mutagenesis
      of its C-terminal domain. Mutating residues in a groove of the TPR domain that
      binds to heat shock protein 90 had no effect on basal phosphatase activity.
      Mutation of Glu-76, however, whose side chain projects away from this groove,
      resulted in a 10-fold elevation of basal activity without affecting arachidonic
      acid-stimulated activity. Thus, the interface of the TPR domain involved in PP5
      autoinhibition appears to be different from that involved in heat shock protein
      90 binding. We also observed a 10-fold elevation of basal phosphatase activity
      upon removing the C-terminal 13 amino acids of PP5, with a concomitant 50%
      decrease in arachidonic acid-stimulated activity. These two effects were
      accounted for by two distinct amino acid deletions: deleting the four C-terminal
      residues (496-499) of PP5 had no effect on its activity, but removing Gln-495
      elevated basal activity 10-fold. Removal of a further three amino acids had no
      additional effect, but deleting Asn-491 resulted in a 50% reduction in
      arachidonic acid-stimulated activity. Thus, Glu-76 in the TPR domain and Gln-495
      at the C-terminus were implicated in maintaining the low basal activity of PP5.
      While the TPR domain alone has been thought to mediate fatty acid activation of
      PP5, our data suggest that Asn-491, near its C-terminus, may also be involved in
      this process.

PMID- 11523990
TI  - Site-directed sulfhydryl labeling of the lactose permease of Escherichia coli:
      helices IV and V that contain the major determinants for substrate binding.
AB  - Helices IV and V in the lactose permease of Escherichia coli contain the major
      determinants for substrate binding [Glu126 (helix IV), Arg144 (helix V), and
      Cys148 (helix V)]. Structural and dynamic features of this region were studied by
      using site-directed sulfhydryl modification of 48 single-Cys replacement mutants
      with N-[(14)C]ethylmaleimide (NEM) in the absence or presence of ligand. In right
      side-out membrane vesicles, Cys residues in the cytoplasmic halves of both
      helices react with NEM in the absence of ligand, while Cys residues in the
      periplasmic halves do not. Five Cys replacement mutants at the periplasmic end of
      helix V and one at the cytoplasmic end of helix V label only in the presence of
      ligand. Interestingly, in addition to native Cys148, a known binding-site
      residue, labeling of mutant Ala122 --> Cys, which is located in helix IV across
      from Cys148, is markedly attenuated by ligand. Furthermore, alkylation of the
      Ala122 --> Cys mutant blocks transport, and protection is afforded by substrate,
      indicating that Ala122 is also a component of the sugar binding site.
      Methanethiosulfonate ethylsulfonate, an impermeant thiol reagent shown clearly in
      this paper to be impermeant in E. coli spheroplasts, was used to identify
      substituted Cys side chains exposed to water and accessible from the periplasmic
      side. Most of the Cys mutants in the cytoplasmic halves of helices IV and V, as
      well as two residues in the intervening loop, are accessible to the aqueous phase
      from the periplasmic face of the membrane. The findings indicate that the
      cytoplasmic halves of helices IV and V are more reactive/accessible to thiol
      reagents and more exposed to solvent than the periplasmic half. Furthermore,
      positions that exhibit ligand-induced changes are located for the most part in
      the vicinity of the residues directly involved in substrate binding, as well as
      the cytoplasmic loop between helices IV and V.

PMID- 11523991
TI  - Membrane-spanning peptides induce phospholipid flop: a model for phospholipid
      translocation across the inner membrane of E. coli.
AB  - The mechanism by which phospholipids translocate (flop) across the E. coli inner
      membrane remains to be elucidated. We tested the hypothesis that the membrane
      spanning domains of proteins catalyze phospholipid flop by their mere presence in
      the membrane. As a model, peptides mimicking the transmembrane stretches of
      proteins, with the amino acid sequence GXXL(AL)(n)XXA (with X = K, H, or W and n
      = 8 or 12), were incorporated in large unilamellar vesicles composed of E. coli
      phospholipids. Phospholipid flop was measured by assaying the increase in
      accessibility to dithionite of a 2,6-(7-nitro-2,1,3-benzoxadiazol-4
      yl)aminocaproyl (C(6)NBD)-labeled phospholipid analogue, initially exclusively
      present in the inner leaflet of the vesicle membrane. Fast flop of C(6)NBD
      phosphatidylglycerol (C(6)NBD-PG) was observed in vesicles in which
      GKKL(AL)(12)KKA was incorporated, with the apparent first-order flop rate
      constant (K(flop)) linearly increasing with peptide:phospholipid molar ratios,
      reaching a translocation half-time of approximately 10 min at a 1:250
      peptide:phospholipid molar ratio at 25 degrees C. The peptides of the series
      GXXL(AL)(8)XXA also induced flop of C(6)NBD-PG, supporting the hypothesis that
      transmembrane parts of proteins mediate phospholipid translocation. In this
      series, K(flop) decreased in the order X = K > H > W, indicating that peptide
      lipid interactions in the interfacial region of the membrane modulate the
      efficiency of a peptide to cause flop. For the peptides tested, flop of C(6)NBD
      phosphatidylethanolamine (C(6)NBD-PE) was substantially slower than that of
      C(6)NBD-PG. In vesicles without peptide, flop was negligible both for C(6)NBD-PG
      and for C(6)NBD-PE. A model for peptide-induced flop is proposed, which takes
      into account the observed peptide and lipid specificity.

PMID- 11523992
TI  - Membrane cholesterol modulates serotonin transporter activity.
AB  - The synaptic actions of the neurotransmitter serotonin are terminated by a
      selective high-affinity reuptake mediated by the serotonin transporter (SERT). To
      gain insight into the modulation of the functional properties of this integral
      membrane protein by cholesterol, a main component of the lipid bilayer, we stably
      expressed the rat SERT in human embryonic kidney 293 cells and, upon altering the
      cholesterol content of these cells by different means, analyzed SERT activity.
      Depletion of the level of membrane cholesterol by treatment with either the
      cholesterol chelating agent methyl-beta-cyclodextrin (MbetaCD), cholesterol
      oxidase, or the cholesterol-binding fluorochrome filipin resulted in a decrease
      in SERT activity due to both a loss of affinity of substrate and ligand binding
      and a concomitant reduction of the maximal transport rate. In cholesterol
      depleted membranes, cholesterol levels could be restored to those found in
      untreated membranes by incubation of the membranes with an MbetaCD-cholesterol
      complex, which correlated with a reversal of the cholesterol depletion-mediated
      decrease in the level of high-affinity binding. This was not the case when other
      steroids, such as ergosterol, 5-cholestene, or pregnenolone, were substituted
      into cholesterol-depleted membranes. These results suggest that membrane
      cholesterol modulates the functional properties of the SERT by specific molecular
      interactions which are needed to stabilize the transporter in its optimally
      active form.

PMID- 11523993
TI  - Protein-induced formation of cholesterol-rich domains.
AB  - A major protein of neuronal rafts, NAP-22, binds specifically to cholesterol. We
      demonstrate by circular dichroism that NAP-22 contains a significant amount of
      beta-structure that is not sensitive to binding of the protein to membranes,
      suggesting that a major portion of the protein does not insert deeply into the
      membrane. The free energy of binding of NAP-22 to liposomes of
      dioleoylphosphatidylcholine with 40% cholesterol is -7.3 +/- 0.5 kcal/mol. NAP-22
      mixed with dipalmitoylphosphatidylcholine and 40% cholesterol partitions into the
      detergent insoluble fraction in the presence of 1% Triton X-100. NAP-22 also
      causes this insoluble fraction to become enriched in cholesterol relative to
      phospholipid, again demonstrating the ability of this protein to segregate
      cholesterol and phospholipids into domains. Differential scanning calorimetry
      results demonstrate that NAP-22 promotes domain formation in liposomes composed
      of cholesterol and phosphatidylcholine. This is shown by NAP-22-promoted changes
      in the shape and enthalpy of the phase transition of phosphatidylcholine as well
      as by the appearance of cholesterol crystallite transitions in membranes composed
      of phosphatidylcholine with either saturated or unsaturated acyl chains. In situ
      atomic force microscopy revealed a marked change in the surface morphology of a
      supported bilayer of dioleoylphosphatidylcholine with 0.4 mole fraction of
      cholesterol upon addition of NAP-22. Prior to the addition of the protein, the
      bilayer appears to be a molecularly smooth structure with uniform thickness.
      Addition of NAP-22 resulted in the rapid formation of localized raised bilayer
      domains. Remarkably, there was no gross disruption or erosion of the bilayer but
      rather simply an apparent rearrangement of the lipid bilayer structure due to the
      interaction of NAP-22 with the lipid. Our results demonstrate that NAP-22 can
      induce the formation of cholesterol-rich domains in membranes. This is likely to
      be relevant in neuronal membrane domains that are rich in NAP-22.

PMID- 11523994
TI  - Regulation of CTP: phosphocholine cytidylyltransferase activity by the physical
      properties of lipid membranes: an important role for stored curvature strain
      energy.
AB  - CTP:Phosphocholine cytidylyltransferase (CT) catalyzes the key step in
      phosphatidylcholine (PC) synthesis. CT is activated by binding to certain lipid
      membranes. The membrane binding affinity of CT can vary from micromolar to
      millimolar K(d), depending on the lipid composition of the target membrane. Class
      II CT activators like diacylglycerols and unsaturated phosphatidylethanolamines
      (PE) favor inverted lipid phase formation. The mechanism(s) governing CT's
      association with class II lipid membranes and subsequent activation are
      relatively unknown. We measured CT activation by vesicles composed of PC and one
      of three unsaturated PEs, dioleoylglycerol (DOG), or cholesterol. For each lipid
      system, we estimated the stored curvature strain energy of the monolayer when
      confined to a relatively flat bilayer. CT binding and activation correlate very
      well with the curvature strain energy of several chemically distinct class II
      lipid systems, with the exception of those containing cholesterol, in which CT
      activation was less than the increase in curvature strain. CT activation by
      membranes containing DOG was reversed by inclusion of specific lysolipids, which
      reduce curvature strain energy. LysoPC, which has a larger positive curvature
      than lysoPE, produced greater inhibition of CT activation. Stored curvature
      strain energy is thus an important determinant of CT activation. Membrane
      interfacial polarity was investigated using a membrane-anchored fluorescent
      probe. Decreases in quenching of this interfacial probe by doxyl-PCs in class II
      membranes suggest the probe adopts a more superficial membrane location. This may
      reflect an increased surface hydrophobicity of class II lipid membranes, implying
      a role for surface dehydration in CT's interactions with membranes containing
      class II lipids. Cholesterol, a poor activator of CT, did not affect the
      positioning of the polarity-sensitive probe, suggesting that one reason for its
      ineffectiveness is an inability to enhance surface hydrophobicity.

PMID- 11523995
TI  - Receptor-G protein gamma specificity: gamma11 shows unique potency for A(1)
      adenosine and 5-HT(1A) receptors.
AB  - G protein coupled receptors activate signal transducing guanine nucleotide
      binding proteins (G proteins), which consist of an alpha subunit and a betagamma
      dimer. Whole cell studies have reported that receptors signal through specific
      betagamma subtypes. Membrane reconstitution studies with the adenosine A(1) and
      alpha(2A) adrenergic receptors have reached a similar conclusion. We aimed to
      test the generality of this finding by comparing the gamma subtype specificity
      for four G(i)-coupled receptors: alpha(2A) adrenergic; A1 adenosine (A(1)-R); 5
      hydroxytryptamine(1A) (5-HT(1A)-R); mu opioid. Membranes were reconstituted with
      Galpha(i)(1) and five gamma subtypes (dimerized to beta1). Using a sensitive
      alpha-betagamma binding assay, we show that all recombinant betagamma (except
      beta1gamma1) had comparable affinity for alpha(i)(1). Using high affinity agonist
      binding as a measure of receptor-G protein coupling, betagamma-containing gamma11
      was the most potent for A(1)-R and 5-HT(1A)-R (p < 0.05, one way ANOVA) while
      gamma7 was most potent for the other two receptors. gamma11 was 3-8-fold more
      potent for the A(1)-R than were the other gamma subtypes. Also, gamma11 was 2-8
      fold more potent for A(1)-R than at the other receptors, suggesting a unique
      coupling specificity of the A(1)-R for gamma11. In contrast, the discrimination
      by receptors for the other betagamma subtypes (beta1 and gamma1, gamma2, gamma7,
      and gamma10) was limited (2-3-fold). Thus the exquisite betagamma specificity of
      individual receptors reported in whole cell studies may depend on in vivo
      mechanisms beyond direct receptor recognition of betagamma subtypes.

PMID- 11523996
TI  - Role of prenylation in the interaction of Rho-family small GTPases with GTPase
      activating proteins.
AB  - The role of prenylation in the interaction of Rho-family small GTPases with their
      GTPase activating proteins (GAPs) was investigated. Prenylated and nonprenylated
      small GTPases were expressed in Sf9 insect cells and Escherichia coli,
      respectively. Nucleotide binding to and hydrolysis by prenylated and
      nonprenylated proteins were identical, but three major differences were observed
      in their reactions with GAPs. (1) Membrane-associated GAPs accelerate GTP
      hydrolysis only on prenylated Rac1 and RhoA, but they are inactive on the
      nonprenylated form of these proteins. The difference is independent of the
      presence of detergents. In contrast to Rac1 and RhoA, nonprenylated Cdc42 is able
      to interact with membrane-localized GAPs. (2) Full-length p50RhoGAP and
      p190RhoGAP react less intensely with nonprenylated Rac1 than with the prenylated
      protein, whereas no difference was observed in the reaction of isolated GAP
      domains of either p50RhoGAP or Bcr with the different types of Rac1. (3) Fluoride
      exerts a significant inhibitory effect only on the interaction of prenylated Rac1
      with the isolated GAP domains of p50RhoGAP or Bcr. The effect of fluoride is not
      influenced by addition or chelation of Al(3+). This is the first detailed study
      demonstrating that prenylation of the small GTPase is an important factor in
      determining its reaction with GAPs. It is suggested that both intramolecular
      interactions and membrane targeting of GAP proteins represent potential
      mechanisms regulating Rac signaling.

PMID- 11523997
TI  - Hydrophobic modulation of heme properties in heme protein maquettes.
AB  - We have investigated the properties of the two hemes bound to histidine in the
      H10 positions of the uniquely structured apo form of the heme binding four-helix
      bundle protein maquette [H10H24-L6I,L13F](2), here called [I(6)F(13)H(24)](2) for
      the amino acids at positions 6 (I), 13 (F) and 24 (H), respectively. The primary
      structure of each alpha-helix, alpha-SH, in [I(6)F(13)H(24)](2) is Ac
      CGGGEI(6)WKL.H(10)EEF(13)LKK.FEELLKL.H(24)EERLKK.L-CONH(2). In our nomenclature,
      [I(6)F(13)H(24)] represents the disulfide-bridged di-alpha-helical homodimer of
      this sequence, i.e., (alpha-SS-alpha), and [I(6)F(13)H(24)](2) represents the
      dimeric four helix bundle composed of two di-alpha-helical subunits, i.e., (alpha
      SS-alpha)(2). We replaced the histidines at positions H24 in [I(6)F(13)H(24)](2)
      with hydrophobic amino acids incompetent for heme ligation. These maquette
      variants, [I(6)F(13)I(24)](2), [I(6)F(13)A(24)](2), and [I(6)F(13)F(24)](2), are
      distinguished from the tetraheme binding parent peptide, [I(6)F(13)H(24)](2), by
      a reduction in the heme:four-helix bundle stoichiometry from 4:1 to 2:1.
      Iterative redesign has identified phenylalanine as the optimal amino acid
      replacement for H24 in the context of apo state conformational specificity.
      Furthermore, the novel second generation diheme [I(6)F(13)F(24)](2) maquette was
      related to the first generation diheme [H10A24](2) prototype, [L(6)L(13)A(24)](2)
      in the present nomenclature, via a sequential path in sequence space to evaluate
      the effects of conservative hydrophobic amino acid changes on heme properties.
      Each of the disulfide-linked dipeptides studied was highly helical (>77% as
      determined from circular dichroism spectroscopy), self-associates in solution to
      form a dimer (as determined by size exclusion chromatography), is
      thermodynamically stable (-DeltaG(H)2(O) >18 kcal/mol), and possesses
      conformational specificity that NMR data indicate can vary from multistructured
      to single structured. Each peptide binds one heme with a dissociation constant,
      K(d1) value, tighter than 65 nM forming a series of monoheme maquettes. Addition
      of a second equivalent of heme results in heme binding with a K(d2) in the range
      of 35-800 nM forming the diheme maquette state. Single conservative amino acid
      changes between peptide sequences are responsible for up to 10-fold changes in
      K(d) values. The equilibrium reduction midpoint potential (E(m7.5)) determined in
      the monoheme state ranges from -156 to -210 mV vs SHE and in the diheme state
      ranges from -144 to -288 mV. An observed heme-heme electrostatic interaction (>70
      mV) in the diheme state indicates a syn global topology of the di-alpha-helical
      monomers. The heme affinity and electrochemistry of the three H24 variants
      studied identify the tight binding sites (K(d1) and K(d2) values <200 nM) having
      the lower reduction midpoint potentials (E(m7.5) values of -155 and -260 mV) with
      the H10 bound hemes in the parent tetraheme state of [H10H24-L6I,L13F](2), here
      called [I(6)F(13)H(24)](2). The results of this study illustrate that
      conservative hydrophobic amino acid changes near the heme binding site can
      modulate the E(m) by up to +/-50 mV and the K(d) by an order of magnitude.
      Furthermore, the effects of multiple single amino acid changes on E(m) and K(d)
      do not appear to be additive.

PMID- 11523998
TI  - Novel heme ligation in a c-type cytochrome involved in thiosulfate oxidation: EPR
      and MCD of SoxAX from Rhodovulum sulfidophilum.
AB  - The SoxAX complex of the bacterium Rhodovulum sulfidophilum is a heterodimeric c
      type cytochrome that plays an essential role in photosynthetic thiosulfate and
      sulfide oxidation. The three heme sites of SoxAX have been analyzed using
      electronic absorption, electron paramagnetic resonance, and magnetic circular
      dichroism spectroscopies. Heme-3 in the ferric state is characterized by a Large
      g(max) EPR signal and has histidine and methionine axial heme iron ligands which
      are retained on reduction to the ferrous state. Hemes-1 and -2 both have thiolate
      plus nitrogenous ligand sets in the ferric state and give rise to rhombic EPR
      spectra. Heme-1, whose ligands derive from cysteinate and histidine residues,
      remains ferric in the presence of dithionite ion. Ferric heme-2 exists with a
      preparation-dependent mixture of two different ligand sets, one being
      cysteinate/histidine, the other an unidentified pair with a weaker crystal-field
      strength. Upon reduction of the SoxAX complex with dithionite, a change occurs in
      the ligands of heme-2 in which the thiolate is either protonated or replaced by
      an unidentified ligand. Sequence analysis places the histidine/methionine
      coordinated heme in SoxX and the thiolate-liganded hemes in SoxA. SoxAX is the
      first naturally occurring c-type cytochrome in which a thiolate-coordinated heme
      has been identified.

PMID- 11523999
TI  - Rapid electron transfer to photosystem I and unusual spectral features of
      cytochrome c(6) in Synechococcus sp. PCC 7002 in vivo.
AB  - Cytochrome c(6) donates electrons to photosystem I (PS I) in Synechococcus sp.
      PCC 7002. In this work, we provide evidence for rapid electron transfer (t(1/2) =
      3 micros) from cytochrome c(6) to PS I in this cyanobacterium in vivo, indicating
      prefixation of the reduced donor protein to the photosystem. We have investigated
      the cytochrome c(6)-PS I interaction by laser flash-induced spectroscopy of
      intact and broken cells and by redox titrations of membrane and supernatant
      fractions. Redox studies revealed the expected membrane-bound cytochrome f, b(6),
      and b(559) species and two soluble cytochromes with alpha-band absorption peaks
      of 551 and 553 nm and midpoint potentials of -100 and 370 mV, respectively. The
      characteristics and the symmetrical alpha-band spectrum of the latter correspond
      to typical cyanobacterial cytochrome c(6) proteins. Rapid oxidation of cytochrome
      c(6) by PS I in vivo results in a unique, asymmetric oxidation spectrum, which
      differs significantly from the spectra obtained for cytochrome c(6) in solution.
      The basis for the unusual cytochrome c(6) spectrum and possible mechanisms of
      cytochrome c(6) fixation to PS I are discussed. The occurrence of rapid electron
      transfer to PS I in cyanobacteria suggests that this mechanism evolved before the
      endosymbiotic origin of chloroplasts. Its selective advantage may lie in
      protection against photo-oxidative damage as shown for Chlamydomonas.

PMID- 11524000
TI  - Ligand binding and the catalytic reaction of cytochrome caa(3) from the
      thermophilic bacterium Rhodothermus marinus.
AB  - The ligand-binding dynamics and the reaction with O(2) of the fully (five
      electron) reduced cytochrome caa(3) from the thermohalophilic bacterium
      Rhodothermus (R.) marinus were investigated. The enzyme is a proton pump which
      has all the residues of the proton-transfer pathways found in the mitochondrial
      like enzymes conserved, except for one of the key elements of the D-pathway, the
      helix-VI glutamate [Glu(I-286), R. sphaeroides numbering]. In contrast to what
      has been suggested previously as general characteristics of thermophilic enzymes,
      during formation of the R. marinus caa(3)-CO complex, CO binds weakly to Cu(B),
      and is rapidly (k(Ba) = 450 s(-1)) trapped by irreversible (K(Ba) = 4.5 x 10(3))
      binding to heme a(3). Upon reaction of the fully reduced enzyme with O(2), four
      kinetic phases were resolved during the first 10 ms after initiation of the
      reaction. On the basis of a comparison to reactions observed with the bovine
      enzyme, these phases were attributed to the following transitions between
      intermediates (pH 7.8, 1 mM O(2)): R --> A (tau congruent with 8 micros), A -->
      P(r) (tau congruent with 35 micros), P(r) --> F (tau congruent with 240 micros),
      F --> O (tau congruent with 2.5 ms), where the last two phases were associated
      with proton uptake from the bulk solution. Oxidation of heme c was observed only
      during the last two reaction steps. The slower transition times as compared to
      those observed with the bovine enzyme most likely reflect the replacement of
      Glu(I-286) of the helix-VI motif -XGHPEV- by a tyrosine in the R. marinus enzyme
      in the motif -YSHPXV-. The presence of an additional, fifth electron in the
      enzyme was reflected by two additional kinetic phases with time constants of
      approximately 20 and approximately 720 ms during which the fifth electron
      reequilibrated within the enzyme.

PMID- 11524001
TI  - Redox properties of human manganese superoxide dismutase and active-site mutants.
AB  - The redox potential of human manganese superoxide dismutase (MnSOD) has been
      difficult to determine because of the problem of finding suitable electron
      mediators. We have found that ferricyanide and pentacyanoaminoferrate can be used
      as electron mediators, although equilibration is very slow with a half-time near
      6 h. Values of the midpoint potential were determined both by allowing enzyme and
      mediators to equilibrate up to 38 h and by reductive titration adding dithionite
      to enzyme and mediator. An overall value of the midpoint potential was found to
      be 393 +/- 29 mV. To elucidate the role of His30 and Tyr34 in the active site of
      human MnSOD, we have also measured the redox properties of the site-specific
      mutants His30Asn (H30N) and Tyr34Phe (Y34F) and compared them with the wild-type
      enzyme. Crystal structures have shown that each mutation interrupts a hydrogen
      bond network in the active site, and each causes a 10-fold decrease in the
      maximal velocity of catalysis of superoxide dismutation as compared with wild
      type. The present study shows that H30N and Y34F human MnSOD have very little
      effect, within experimental uncertainty, on the redox potential of the active
      site metal. The redox potentials determined electrochemically were 365 +/- 28 mV
      for H30N and 435 +/- 30 mV for Y34F MnSOD. These results suggest that the role of
      His30 and Tyr34 is more in support of catalysis, probably proton transport, and
      not in the tuning of the redox potential.

PMID- 11524002
TI  - Laser flash induced electron transfer in P450cam monooxygenase: putidaredoxin
      reductase-putidaredoxin interaction.
AB  - The P450cam monooxygenase from Pseudomonas putida consists of three redox
      proteins: NADH-putidaredoxin reductase (Pdr), putidaredoxin (Pdx), and cytochrome
      P450cam. The redox properties of the FAD-containing Pdr and the mechanism of Pdr
      Pdx complex formation are the least studied aspects of this system. We have
      utilized laser flash photolysis techniques to produce the one-electron-reduced
      species of Pdr, to characterize its spectral and electron-transferring
      properties, and to investigate the mechanism of its interaction with Pdx. Upon
      flash-induced reduction by 5-deazariboflavin semiquinone, the flavoprotein forms
      a blue neutral FAD semiquinone (FADH(*)). The FAD semiquinone was unstable and
      partially disproportionated into fully oxidized and fully reduced flavin. The
      rate of FADH(*) decay was dependent on ionic strength and NAD(+). In the mixture
      of Pdr and Pdx, where the flavoprotein was present in excess, electron transfer
      (ET) from FADH(*) to the iron-sulfur cluster was observed. The Pdr-to-Pdx ET
      rates were maximal at an ionic strength of 0.35 where a kinetic dissociation
      constant (K(d)) for the transient Pdr-Pdx complex and a limiting k(obs) value
      were equal to 5 microM and 226 s(-1), respectively. This indicates that FADH(*)
      is a kinetically significant intermediate in the turnover of P450cam
      monooxygenase. Transient kinetics as a function of ionic strength suggest that,
      in contrast to the Pdx-P450cam redox couple where complex formation is
      predominantly electrostatic, the Pdx-Pdr association is driven by
      nonelectrostatic interactions.

PMID- 11524003
TI  - Thiolate-imidazolium ion pair is not an obligatory catalytic entity of cysteine
      peptidases: the active site of picornain 3C.
AB  - Cysteine peptidases are thought to attack the substrate by a thiolate-imidazolium
      ion-pair, as demonstrated with the most extensively studied papain. Picornavirus
      proteinases (picornains), a different family of cysteine peptidases, are
      structurally related to the trypsin family of serine peptidases, whose
      catalytically competent histidine operates as a general base catalyst. Measuring
      the absorbance change upon alkylation of picornains at 250 nm, where the
      nondissociated thiol group has a negligible absorbance relative to the ionized
      form, one can test the ionization state of the catalytic cysteine. For such
      studies, we have prepared and used a mutated variant of the poliovirus proteinase
      3C, which contains a single thiol group. The pH dependence of the molar
      extinction coefficient has undoubtedly shown that picornain 3C contains an
      ordinary thiol group rather than the usual ion-pair. Therefore, the imidazole
      assistance, demonstrated in alkylation reactions, is presumably general base
      catalysis, as found with serine peptidases. Kinetic studies on k(cat)/K(m) gave
      large inverse deuterium isotope effects, which may overcompensate the reverse
      values characteristic of the potential general base catalysis. The inverse
      effects is associated with the stabilization of the protein structure in heavy
      water.

PMID- 11524004
TI  - Physiological implications of the contrasting modulation of the activities of the
      epsilon- and zeta-isoforms of diacylglycerol kinase.
AB  - We have shown that the requirement of the epsilon-isoform of diacylglycerol
      kinase for diacylglycerols containing arachidonic acid is specific for this
      substrate and cannot be replaced by the presence of an arachidonoyl group in
      other places in the membrane; rather, it has to be present on the substrate
      itself. In addition, we demonstrate that the increased activity shown toward 1
      stearoyl-2-arachidonoylglycerol by the epsilon-isoform of diacylglycerol kinase
      is not a consequence of altered membrane physical properties but is rather a
      specific interaction with the arachidonoyl group. We have also compared the
      modulation of the activity of the epsilon-isoform of diacylglycerol kinase with
      that of the zeta-isoform with regard to some of the intermediates involved in
      phosphatidylinositol cycling. One of the products of the hydrolysis of
      phosphatidylinositol diphosphate is diacylglycerol enriched in arachidonic acid.
      The activity of the epsilon-isoform is known to be specific for this form of
      diacylglycerol. We show that in contrast, the activity of the zeta-isoform is
      lower against 1-stearoyl-2-arachidonoylglycerol compared with dioleoylglycerol.
      We demonstrate that addition of phosphatidylserine, as well as other anionic
      phospholipids including L-alpha-phosphatidylinositol 4,5-bisphosphate, strongly
      inhibits the epsilon-isoform, but these anionic lipids increase the activity of
      the zeta-isoform. Addition of Ca(2+), which is released from internal stores as a
      consequence of phosphatidylinositol cycling, promotes the activity of the epsilon
      isoform of this enzyme but has little effect on the zeta-isoform. The contrasting
      conditions required for maximal activity of these two isoforms of diacylglycerol
      kinase, as well as their different substrate specificity, suggest that they have
      different physiological roles in signal transduction.

PMID- 11524006
TI  - Regulation of human cystathionine beta-synthase by S-adenosyl-L-methionine:
      evidence for two catalytically active conformations involving an autoinhibitory
      domain in the C-terminal region.
AB  - Cystathionine beta-synthase (CBS), condensing homocysteine and serine, represents
      a key regulatory point in the biosynthesis of cysteine via the transsulfuration
      pathway. Inherited deficiency of CBS causes homocystinuria. CBS is activated by S
      adenosyl-L-methionine (AdoMet) by inducing a conformational change involving a
      noncatalytic C-terminal region spanning residues 414-551. We report the
      purification of two patient-derived C-terminal mutant forms of CBS, S466L and
      I435T, that provide new insight into the mechanism of CBS regulation and indicate
      a regulatory function for the "CBS domain". Both of these point mutations confer
      catalytically active proteins. The I435T protein is AdoMet inducible but is 10
      fold less responsive than wild-type (WT) CBS to physiologically relevant
      concentrations of this compound. The S466L form does not respond to AdoMet but is
      constitutively activated to a level intermediate between those of WT CBS in the
      presence and absence of AdoMet. Both mutant proteins are able to bind AdoMet,
      indicating that their impairment is related to their ability to assume the fully
      activated conformation that AdoMet induces in WT CBS. We found that I435T and WT
      CBS can be activated by partial thermal denaturation but that the AdoMet
      stimulated WT, S466L, and a truncated form of CBS lacking the C-terminal region
      cannot be further activated by this treatment. Tryptophan and PLP fluorescence
      data for these different forms of CBS indicate that activation by AdoMet, limited
      proteolysis, and thermal denaturation share a common mechanism involving the
      displacement of an autoinhibitory domain located in the C-terminal region of the
      protein.

PMID- 11524005
TI  - Contribution of aromatic-aromatic interactions to the anomalous pK(a) of tyrosine
      9 and the C-terminal dynamics of glutathione S-transferase A1-1.
AB  - Most cytosolic glutathione S-transferases (GSTs) exploit a hydrogen bond between
      an active site Tyr and the bound glutathione (GSH) cofactor to lower the pK(a) of
      the GSH and generate the nucleophilic thiolate anion, GS(-). In human (hGSTA1-1)
      and rat (rGSTA1-1) homologues, the active site Tyr-9 has a low pK(a) of 8.1-8.3,
      for which the functional significance is unknown. Crystal structures of GSTA1-1
      suggest that weakly polar interactions between the electropositive ring edge of
      Phe-10 and the pi-cloud of Tyr-9, in the apoenzyme, could stabilize the
      tyrosinate anion and also modulate the pK(a) of GSH. Upon binding a product GSH
      conjugate, Phe-10 moves away from Tyr-9, allowing the highly dynamic C-terminus
      to "close" over the active site. To explore the role of Phe-10 in modulating the
      Tyr-9 pK(a) and in ligand binding, rGSTA1-1 mutants F10Y, F10L, and F10A were
      characterized. The pK(a)s of Tyr-9 in the apoenzymes were 8.2 +/- 0.2, 8.7 +/-
      0.2, and 9.3 +/- 0.1, respectively, for F10Y, F10L, and F10A, compared to 8.3 +/-
      0.2 for the "wild type". The experimentally determined pK(a)s qualitatively
      paralleled the energies required to remove a proton predicted by ab initio
      calculations using model compounds constrained to the coordinates of rGSTA1-1.
      The pK(a) of GSH in the binary complex was significantly less affected by these
      substitutions. In contrast, F220I and F220Y C-terminal mutations caused the pK(a)
      of Tyr-9 to decrease modestly. For the binary complex with S-hexyl-GSH, which
      induces the "closed" conformation, Tyr-9 retains a low pK(a) and the Phe-10
      substitutions have significant effects. Presumably, Phe-10 plays a critical
      structural role in stabilizing the closed conformation. The mutations F10L and
      F10A also slowed the rate of GSH conjugate binding by 10-20-fold, as measured by
      stopped-flow fluorescence. The effects of Phe-10 substitution were large for both
      steps of the biphasic binding reaction, suggesting the importance of aromatic
      interactions throughout the reaction coordinate. A unified view of the C-terminal
      dynamics of GSTA1-1 is discussed, which emphasizes the coupling between Tyr-9
      ionization, active site solvation, and C-terminal dynamics.

PMID- 11524007
TI  - Cation-dependent stability of subtilisin.
AB  - Subtilisin BPN' contains two cation binding sites. One specifically binds calcium
      (site A), and the other can bind both divalent and monovalvent metals (site B).
      By binding at specific sites in the tertiary structure of subtilisin, cations
      contribute their binding energy to the stability of the native state and increase
      the activation energy of unfolding. Deconvoluting the influence of binding sites
      A and B on the inactivation rate of subtilisin is complicated, however. This
      paper examines the stabilizing effects of cation binding at site B by using a
      mutant of subtilisin BPN' which lacks calcium site A. Using this mutant, we show
      that calcium binding at site B has relatively little effect on stability in the
      presence of moderate concentrations of monovalent cations. At [NaCl] =100 mM,
      site B is >or=98% occupied with sodium, and therefore its net occupancy with a
      cation varies little as subtilisin is titrated with calcium. Exchanging sodium
      for calcium results in a 5-fold decrease in the rate of inactivation. In
      contrast, because of the high selectivity of site A for calcium, its occupancy
      changes dramatically as calcium concentration is varied, and consequently the
      inactivation rate of subtilisin decreases approximately 200-fold as site A
      becomes saturated with calcium, irrespective of the concentration of monovalent
      cations.

PMID- 11524008
TI  - Stabilizing mutations and calcium-dependent stability of subtilisin.
AB  - Stability is a property of subtilisin which has proven particularly amenable to
      enhancement via random mutagenesis and screening, yet the effects of most
      stabilizing mutations are not understood in structural and energetic detail. This
      paper seeks to explain the longstanding observation that stabilizing mutations
      are usually calcium-dependent in their stabilizing effect, irrespective of their
      proximity to the calcium binding sites. Stabilizing mutations in subtilisin fall
      into one of three classes. The largest class of mutations stabilize only in the
      presence of excess calcium. A smaller number of mutations stabilize independently
      of [calcium], and a few mutations stabilize only in the presence of chelating
      agents, such as EDTA. This study compares the effects of mutations from each
      class when introduced into subtilisin BPN' and two calcium-free versions of
      subtilisin. The calcium-dependent effects of mutations can be explained by
      considering subtilisin to be in conformational equilibrium between two
      structurally similar but energetically distinct states: N and N*. The equilibrium
      from the N* to the N state can be altered either by calcium binding to site A or
      by mutation. Mutations which stabilize only in the presence of calcium stabilize
      the N state relative to N*. Mutations which stabilize only in the presence of
      chelants stabilize the N* state relative to N. As a byproduct of this analysis,
      we have developed a hyperstable variant of subtilisin whose inactivation at high
      temperature in the presence of EDTA is 10(5) times slower than wild-type
      subtilisin.

PMID- 11524009
TI  - Steady-state kinetic characterization of substrates and metal-ion specificities
      of the full-length and N-terminally truncated recombinant human methionine
      aminopeptidases (type 2).
AB  - The steady-state kinetics of a full-length and truncated form of the type 2 human
      methionine aminopeptidase (hMetAP2) were analyzed by continuous monitoring of the
      amide bond cleavage of various peptide substrates and methionyl analogues of 7
      amido-4-methylcoumarin (AMC) and p-nitroaniline (pNA), utilizing new fluorescence
      based and absorbance-based assay substrates and a novel coupled-enzyme assay
      method. The most efficient substrates for hMetAP2 appeared to be peptides of
      three or more amino acids for which the values of k(cat)/K(m) were approximately
      5 x 10(5) M(-1) min(-1). It was found that while the nature of the P1' residue of
      peptide substrates dictates the substrate specificity in the active site of
      hMetAP2, the P2' residue appears to play a key role in the kinetics of
      peptidolysis. The catalytic efficiency of dipeptide substrates was found to be at
      least 250-fold lower than those of the tripeptides. This substantially diminished
      catalytic efficiency of hMetAP2 observed with the alternative substrates MetAMC
      and MetpNA is almost entirely due to the reduction in the turnover rate (k(cat)),
      suggesting that cleavage of the amide bond is at least partially rate-limiting.
      The 107 N-terminal residues of hMetAP2 were not required for either the
      peptidolytic activity of the enzyme or its stability. Steady-state kinetic
      comparison and thermodynamic analyses of an N-terminally truncated form and full
      length enzyme yielded essentially identical kinetic behavior and physical
      properties. Addition of exogenous Co(II) cation was found to significantly
      activate the full-length hMetAP2, while Zn(II) cation, on the other hand, was
      unable to activate hMetAP2 under any concentration that was tested.

PMID- 11524010
TI  - Heterocycle formation in vibriobactin biosynthesis: alternative substrate
      utilization and identification of a condensed intermediate.
AB  - The iron-chelating peptide vibriobactin of the pathogenic Vibrio cholerae is
      assembled by a four-subunit nonribosomal peptide synthetase complex, VibE, VibB,
      VibH, and VibF, using 2,3-dihydroxybenzoate and L-threonine as precursors to two
      2,3-dihydroxyphenyl- (DHP-) methyloxazolinyl groups in amide linkage on a
      norspermidine scaffold. We have tested the ability of the six-domain VibF subunit
      (Cy-Cy-A-C-PCP-C) to utilize various L-threonine analogues and found the beta
      functionalized amino acids serine and cysteine can function as alternate
      substrates in aminoacyl-AMP formation (adenylation or A domain), aminoacyl-S
      enzyme formation (A domain), acylation by 2,3-dihydrobenzoyl- (DHB-) S-VibB
      (heterocyclization or Cy domain), heterocyclization to DHP-oxazolinyl- and DHP
      thiazolinyl-S-enzyme forms of VibF (Cy domain) as well as transfer to DHB
      norspermidine at both N(5) and N(9) positions (condensation or C domain) to make
      the bis(oxazolinyl) and bis(thiazolinyl) analogues of vibriobactin. When L
      threonyl-S-pantetheine or L-threonyl-S-(N-acetyl)cysteamine was used as a small
      molecule thioester analogue of the threonyl-S-VibF acyl enzyme intermediate, the
      Cy domain(s) of a CyCyA fragment of VibF generated DHB-threonyl-thioester
      products of the condensation step but not the methyloxazolinyl thioesters of the
      heterocyclization step. This clean separation of condensation from cyclization
      validates a two-stage mechanism for threonyl, seryl, and cysteinyl
      heterocyclization domains in siderophore and antibiotic synthetases. Full
      heterocyclization activity could be restored by providing CyCyA with the
      substrate L-threonyl-S-peptidyl carrier protein (PCP)-C2, suggesting an important
      role for the protein scaffold component of the heterocyclization acceptor
      substrate. We also examined heterocyclization donor substrate specificity at the
      level of acyl group and protein scaffold and observed intolerance for
      substitution at either position.

PMID- 11524011
TI  - Conformation of the gamma subunit at the gamma-epsilon-c interface in the
      complete Escherichia coli F(1)-ATPase complex by site-directed spin labeling.
AB  - Structure-function relationships of the gamma-epsilon-c subunit interface of
      F(O)F(1) ATP synthase, a region of subunit interactions important in coupling
      between catalysis and transport, were investigated by site-directed spin labeling
      and electron paramagnetic resonance (EPR) spectroscopy. The EPR line widths and
      collision accessibilities of 18 spin-labeled, unique cysteine F(1) mutants from
      gammaLeu198 to gammaLeu215 indicate an alternating pattern in the mobility and
      accessibility parameters for positions gamma201-209, which is reminiscent of a
      beta-strand. Labels at positions gamma204 and gamma210 show tertiary contact upon
      F(1) binding to F(O) and gammaD210C has reduced coupling efficiency. gammaE208C
      could not be spin labeled, but the uncoupling effects of gammaE208K are
      suppressed by second-site mutations in the polar loop of subunit c [Ketchum, C.
      J. and Nakamoto, R. K. (1998) J. Biol. Chem. 273, 22292-22297]. The restricted
      mobility and accessibility of spin labels in the odd-numbered positions between
      gamma201 and gamma207 plus the 2-4-fold higher values in k(cat) for ATP
      hydrolysis of these same mutant F(1) indicate that the interactions of these
      residues with the epsilon subunit mediate its inhibitory activity. Disrupted
      interactions with epsilon subunit also cause reduced coupling efficiency. We
      propose a model for the gamma-epsilon-c interface of Escherichia coli F(O)F(1)
      ATP synthase in which side chains from the odd-numbered residues of the
      gammaLys201-gammaTyr207 beta-strand directly and functionally interact with the
      epsilon subunit, while the even-numbered, acidic residues gammaAsp204,
      gammaGlu208, and gammaAsp210 interact with the F(O) sector, probably with subunit
      c. gamma Subunit interactions with both subunits in this region are important for
      coupling efficiency.

PMID- 11524012
TI  - Distinct site specificity of two pea histone deacetylase complexes.
AB  - We report on the site specificity of two intact pea histone deacetylase
      complexes. HD1 deacetylates lysines 5 and 16 of H4 in the order K16 > K5, while
      in the case of H3 the preferred order is K4 >> K18 approximately K9. The
      specificity of the HD2 complex is markedly different. The preferred residues in
      H4 are K8 approximately K5 > K16, while in H3 deacetylation, the complex HD2
      prefers sites 4 and 18. To obtain these results, we have used a novel procedure
      based on the SPOT technique, a method to synthesize peptides on membrane
      supports. Different sets of membranes with sequentially overlapping histone
      peptides containing acetylated lysines in the sites corresponding to all in vivo
      acetylatable residues were incubated with the complexes. The acetyl groups
      removed by the deacetylase activity were then replaced by radioactive acetate by
      treating the membranes with labeled acetic anhydride. The subsequent counting of
      the membranes allows the quantification of the acetate removal in the histone
      deacetylase reaction in a way that circumvents some of the inconveniences of
      other available procedures.

PMID- 11524013
TI  - Diepoxybutane and diepoxyoctane interstrand cross-linking of the 5S DNA
      nucleosomal core particle.
AB  - Diepoxyalkanes form interstrand cross-links in DNA oligomers preferentially at 5'
      GNC sites. We have examined cross-linking by 1,2,3,4-diepoxybutane (DEB) and
      1,2,7,8-diepoxyoctane (DEO) within a fragment of the 5S RNA gene of Xenopus
      borealis in both the free and nucleosomal states. Sites and efficiencies of
      interstrand cross-linking were probed through denaturing polyacrylamide gel
      electrophoresis and quantitative phosphorimagery. Both agents targeted 5'-GNC
      sites for cross-linking in the restriction fragment in its free state, and DEO
      also targeted 5'-GNNC sites. Monoalkylation occurred at all deoxyguanosines. The
      sites for both monoalkylation and interstrand cross-linking were similar in
      nucleosomal and free DNA, and cross-linked DNA was cleanly incorporated into the
      core particle structure. These findings suggest that the 5S core particle is able
      to tolerate any structural abnormalities induced by diepoxide cross-linking.

PMID- 11524014
TI  - Membrane immunoglobulins are stabilized by interchain disulfide bonds occurring
      within the extracellular membrane-proximal domain.
AB  - Membrane-bound immunoglobulins have, in addition to the transmembrane and
      cytoplasmic portions, an extracellular membrane-proximal domain (EMPD), absent in
      the secretory forms. EMPDs of immunoglobulin isotypes alpha, gamma, and epsilon
      contain cysteines whose role has so far not been elucidated. Using a genetic
      strategy, we investigated the ability of these cysteines to form disulfide
      bridges. Shortened versions of human membrane immunoglobulins, depleted of
      cysteines known to form intermolecular disulfide bonds, were constructed and
      expressed on the surface of a B-cell line. The resulting membrane proteins
      contain a single chain fragment of variable regions (scFv) linked to the
      dimerizing domain from the immunoglobulin heavy chains (CH3 for alpha and gamma
      or CH4 for epsilon isotypes), followed by the corresponding EMPD and the
      transmembrane and cytoplasmic domains. The two functional membrane versions of
      the epsilon chain, containing the short and long EMPD, were analyzed. Our results
      show that the single cysteine within alpha1L and gamma1 EMPD and the short
      version of epsilon EMPD form an interchain disulfide bond. Conversely, the
      cysteine resident in the epsilon transmembrane domain remains unreacted. epsilon
      long EMPD contains four cysteines; two are involved in interchain bonds while the
      remaining two are likely forming an intrachain bridge. Expression of a full
      length membrane epsilon heavy chain mutant, in which Cys(121) and Cys(209) within
      domain CH2 (involved in interchain bridges) were mutated to alanines, confirmed
      that, within the complete IgE, EMPD cysteines form interchain disulfide bonds. In
      conclusion, we unveil evidence for additional covalent stabilization of membrane
      bound immunoglobulins.

PMID- 11524015
TI  - Purification and functional analysis of a novel leucine-zipper/nucleotide-fold
      protein, BZAP45, stimulating cell cycle regulated histone H4 gene transcription.
AB  - Regulation of histone gene transcription at the G1/S phase transition via the
      Site II cell cycle control element is distinct from E2F-dependent mechanisms
      operative at the growth factor-related restriction point. E2F-independent
      activation of histone H4 gene expression combines contributions of several
      promoter factors, including HiNF-M/IRF2 and the HiNF-D/CDP-cut complex which
      contains pRB, CDK1, and cyclin A as non-DNA binding subunits. Mutational analyses
      suggest additional rate-limiting factors for Site II function. Using sequence
      specific Site II DNA affinity chromatography, we identified a 45 kDa protein
      (KIAA0005 or BZAP45) that is embryonically expressed and phylogenetically
      conserved. Based on amino acid sequence analysis, BZAP45 contains a unique
      decapeptide that is part of a putative leucine-zipper protein with a nucleotide
      (ATP or GTP) binding fold. Bacterial expression of a full-length cDNA produces a
      45 kDa protein. Binding studies reveal that highly purified BZAP45 does not
      interact with Site II, suggesting that BZAP45 function may require partner
      proteins. Forced expression of BZAP45 strongly stimulates H4 promoter (nt -215 to
      -1)/CAT reporter gene activity. Deletion analyses and point mutations indicate
      that BZAP45 enhances H4 gene transcription through Site II. Thus, BZAP45 is a
      novel regulatory factor that contributes to transcriptional control at the G1/S
      phase transition.

PMID- 11524016
TI  - A monomer is the minimum functional unit required for channel and ATPase activity
      of the cystic fibrosis transmembrane conductance regulator.
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR) normally functions
      as a phosphorylation-regulated chloride channel on the apical surface of
      epithelial cells, and lack of this function is the primary cause for the fatal
      disease cystic fibrosis (CF). Previous studies showed that purified,
      reconstituted CFTR can function as a chloride channel and, further, that its
      intrinsic ATPase activity is required to regulate opening and closing of the
      channel gate. However, these previous studies did not identify the quaternary
      structure required to mediate conduction and catalysis. Our present studies show
      that CFTR molecules may self-associate in CHO and Sf9 membranes, as complexes
      close to the predicted size of CFTR dimers can be captured by chemical cross
      linking reagents and detected using nondissociative PAGE. However, CFTR function
      does not require a multimeric complex for function as we determined that
      purified, reconstituted CFTR monomers are sufficient to mediate regulated
      chloride conduction and ATPase activity.

PMID- 11524017
TI  - Slow photo-cross-linking kinetics of benzophenone-labeled voltage sensors of ion
      channels.
AB  - Voltage-gated ion channels have voltage sensors that move in response to changes
      in membrane potential. This movement regulates the gates that control access of
      ions to the permeation pathway. To study the coupling between voltage sensors and
      gates, we immobilize the voltage sensors, using a bifunctional photo-cross
      linking reagent that can be attached to an introduced cysteine, and observe the
      consequences for gate movement [Horn, R., Ding, S., and Gruber, H. J. (2000) J.
      Gen. Physiol. 116, 461-475]. UV irradiation of the benzophenone adduct attached
      to the cysteine residue immobilizes the voltage sensors, S4 segments, of both
      Na(+) and Shaker K(+) channels. Here we examine the kinetics of S4 immobilization
      after a brief UV flash. Immobilization has an exponential time course with time
      constants of >200 ms for Shaker and 17 ms for Na(+) channels, whereas the triplet
      excited state lifetime of the benzophenone adduct is <1 ms. This result suggests
      that H-atom abstraction by benzophenone is rapid and that the rate-limiting step
      in immobilization is the recombination of alkyl and ketyl free radicals generated
      by H-abstraction. H-Abstraction is also 2.7-fold more efficient at a
      hyperpolarized voltage than at a depolarized membrane potential in Shaker S4
      segments. S4 immobilization after a UV flash can be prevented by depolarization
      of Shaker channels, suggesting that movement in the activation pathway is capable
      of separating the ketyl and alkyl free radicals. Exploiting the unique charge
      movement and gating properties of the L382V mutant of Shaker, we show that free
      radical separation follows S4 movement itself and is relatively independent of
      the movement of activation gates.

PMID- 11524018
TI  - Quaternary and domain structure of glycoprotein processing glucosidase II.
AB  - Glucose trimming from newly synthesized glycoproteins regulates their interaction
      with the calnexin/calreticulin chaperone system. We have recently proposed that
      glucosidase II consisted of two different subunits, alpha and beta. The alpha
      subunit is the catalytic component, and deletion of its homologue in yeast
      obliterates glucosidase II activity. Deletion of the homologue of the
      noncatalytic beta subunit in Schizosaccharomices pombe drastically reduces
      glucosidase II activity, but the role of the beta subunit in glucosidase II
      activity has not been established. Furthermore, a direct interaction between
      alpha and beta subunits has not been demonstrated. Using chemical cross-linking
      and hydrodynamic analysis by analytical ultracentrifugation, we found that the
      two subunits form a defined complex, composed of one catalytic subunit and one
      accessory subunit (alpha(1)beta(1)) with a molecular mass of 161 kDa. The complex
      had an s value of 6.3 S, indicative of a highly nonglobular shape. The asymmetric
      shape of the alpha(1)beta(1) complex was confirmed by its high susceptibility to
      proteases. The beta subunit could be proteolytically removed from the
      alpha(1)beta(1) complex without affecting catalysis, demonstrating that it is not
      required for glucosidase II activity in vitro. Furthermore, we isolated a
      monomeric C-terminal fragment of the alpha subunit, which retained full
      glucosidase activity. We conclude that the catalytic core of glucosidase II
      resides in a globular domain of the alpha subunit, which can function
      independently of the beta subunit, while the complete alpha and beta subunits
      assemble in a defined heterodimeric complex with a highly extended conformation,
      which may favor interaction with other proteins in the endoplasmic reticulum
      (ER). Through its C-terminal HDEL signal, the beta subunit may retain the
      complete alpha(1)beta(1) complex in the ER.

PMID- 11524019
TI  - Activity and stability of a thermostable alpha-amylase compared to its mesophilic
      homologue: mechanisms of thermal adaptation.
AB  - To elucidate how enzymes adapt to extreme environmental conditions, a comparative
      study with a thermostable alpha-amylase from Bacillus licheniformis (BLA) and its
      mesophilic homologue from Bacillus amyloliquefaciens (BAA) was performed. We
      measured conformational stability, catalytic activity, and conformational
      fluctuations on the picosecond time scale for both enzymes as a function of
      temperature. The objective of this study is to analyze how these properties are
      related to each other. BLA shows its maximal catalytic activity at about 90-95
      degrees C and a strongly reduced activity (only 20% of the maximum) at room
      temperature. Although B. licheniformis itself is a mesophilic organism, BLA shows
      an activity profile typical for a thermophilic enzyme. In contrast to this, BAA
      exhibits its maximal activity at about 80 degrees C but with a level of about 60%
      activity at room temperature. In both cases the unfolding temperatures T(m) are
      only 6 degrees C (BAA, T(m) = 86 degrees C) and 10 degrees C (BLA, T(m) = 103
      degrees C), respectively, higher than the temperatures for maximal activity. In
      contrast to many previous studies on other thermophilic-mesophilic pairs, in this
      study a higher structural flexibility of the thermostable BLA was measured as
      compared to the mesophilic BAA. The findings of this study neither indicate a
      proportionality between the observed dynamics and the catalytic activity nor
      support the idea of more "rigid" thermostable proteins, as often proposed in the
      concept of "corresponding states".

PMID- 11524020
TI  - Flexibility and bioactivity of insulin: an NMR investigation of the solution
      structure and folding of an unusually flexible human insulin mutant with
      increased biological activity.
AB  - The structure and folding of a novel human insulin mutant, [Thr(B27) --> Pro,
      Pro(B28) --> Thr]insulin (PT insulin), in aqueous solution and in mixtures of
      water and 2,2,2-trifluoroethanol (TFE) have been studied by NMR spectroscopy. It
      was found that PT insulin has a highly flexible structure in pure water and is
      present in at least two different conformations, although with an overall
      tertiary structure similar to that of native insulin. Furthermore, the native
      helical structures are poorly defined. Surprisingly, the mutant has a biological
      activity about 50% higher than native insulin. In contrast, in TFE/water solution
      the mutant reveals a propensity of forming a well-defined structure at the
      secondary structure level, similar to monomeric native insulin. Thus, as shown by
      a detailed determination of the structure from 208 distance restraints and 52
      torsion angle restraints by distance geometry, simulated annealing, and
      restrained energy minimization, the native insulin helices (A2-A7, A13-A19, and
      B10-B19) as well as the beta-turn (B20-B23) are formed in 35% TFE. However, the
      amount of tertiary structure is decreased significantly in TFE/water solution.
      The obtained results suggest that only an overall tertiary fold, as observed for
      PT insulin in pure water, is necessary for expressing the biological activity of
      insulin, as long as the molecule is flexible and retains the propensity to form
      the secondary structure required for its receptor binding. In contrast, a compact
      secondary structure, as found for native insulin in solution, is unnecessary for
      the biological activity. A model for the receptor binding of insulin is suggested
      that relates the increased bioactivity to the enhanced flexibility of the mutant.

PMID- 11524021
TI  - Brain and spinal cord atrophy in multiple sclerosis: role as a surrogate measure
      of disease progression.
AB  - Magnetic resonance imaging (MRI) reveals that brain and spinal cord atrophy occur
      early in the course of multiple sclerosis (MS), far earlier than originally
      anticipated. This has important implications for the early treatment of patients
      with MS, as atrophy is thought to reflect destructive, irreversible pathology,
      and subclinical impairment if not overt disability. Several recent trials in MS
      have included atrophy as a secondary or exploratory measure of treatment
      efficacy. While measured cerebral volume or spinal cord area changes are small
      over 1 to 3 year intervals, they are sufficiently large that with current
      methodologies the atrophy measures should provide conclusive information as to
      the effectiveness of therapeutic interventions in halting progressive atrophy.
      Atrophy measures may also provide an important metric for the evaluation of
      disease in primary progressive MS, and in testing combined therapies and
      neuroprotective agents, where conventional MRI methodologies may be relatively
      weak.

PMID- 11524022
TI  - Homocysteine levels in patients with stroke: clinical relevance and therapeutic
      implications.
AB  - High plasma levels of the amino acid homocysteine have been implicated in the
      development of vascular diseases, including stroke. Elevated plasma levels of
      total homocysteine (tHcy) above 15 micromol/L are present in less than 5% of the
      general population, but in as many as 50% of patients with stroke (and other
      atherothromboembolic vascular diseases). However, it remains uncertain whether a
      high tHcy level is a causal risk factor for stroke and should be lowered, or is a
      marker of another factor associated with stroke (e.g. acute tissue damage or
      tissue repair after an acute vascular event) and therefore should not be lowered.
      Plasma levels of tHcy can be lowered effectively by folic acid, vitamin B(6) and
      vitamin B(12) supplementation, and controlled trials have shown some beneficial
      effects on surrogate markers of vascular function. However, these markers are not
      established vascular risk factors or valid predictors of 'hard' clinical vascular
      outcome events. Until it has been shown in large randomised trials [such as the
      ongoing Vitamins to Prevent Stroke Study (VITATOPS) and the Vitamins in Stroke
      Prevention (VISP) study] that multivitamin therapy reduces the rate of recurrent
      stroke and other serious vascular events in patients with prior stroke or
      transient ischaemic attack, widespread screening for, and treatment of, high tHcy
      levels remains experimental and cannot be recommended.

PMID- 11524023
TI  - Aetiology and treatment of sleep disturbances during perimenopause and
      postmenopause.
AB  - The sudden and predictable cessation of ovarian endocrinological function at
      menopause results in a marked decrease of endogenous estrogen and progestogen
      secretion. In addition to cessation of menstruation, a wide range of biological
      functions, including sleep, are affected. Sleep disturbances are more common in
      women than in men and their incidence increases with age. There are 2 distinct
      mechanisms by which menopause is known to affect sleep quality. One is menopausal
      insomnia, which can be considered as part of the symptomatology of the
      climacterium. Another is sleep-disordered breathing, where impairment of sleep
      quality is secondary to sleep apnoea or partial upper airway obstruction during
      sleep. The former is effectively controlled with conventional estrogen
      replacement therapy, whereas the latter could potentially be improved with
      progestogens. Many age-related conditions without a direct link with the
      menopause should also be considered when treating postmenopausal sleep disorders.

PMID- 11524024
TI  - Combination nicotine replacement therapy for smoking cessation: rationale,
      efficacy and tolerability.
AB  - Currently available nicotine replacement therapy (NRT) medications provide
      effective treatment for tobacco dependence, typically doubling success rates
      compared with placebo. A strategy for further improving the efficacy of NRT is to
      combine one medication that allows for passive nicotine delivery (e.g.
      transdermal patch) with another medication that permits ad libitum nicotine
      delivery (e.g. gum, nasal spray, inhaler). The rationale for combining NRT
      medications is that smokers may need both a slow delivery system to achieve a
      constant concentration of nicotine to relieve cravings and tobacco withdrawal
      symptoms, as well as a faster acting preparation that can be administered on
      demand for immediate relief of breakthrough cravings and withdrawal symptoms.
      This article reviews 5 published studies that have examined the effectiveness of
      combination NRT compared with monotherapy in providing withdrawal relief and
      smoking cessation, and examines other factors relevant to the promotion of
      combination NRT for treating tobacco dependence. The data show that there are
      conditions under which combinations of NRT products provide greater efficacy in
      relieving withdrawal and enabling cessation than monotherapy, but the findings
      are not robust and additional research is warranted to better understand the
      magnitude and generality of the benefits of combination therapy. There are also
      regulatory and commercial obstacles that must be considered. Nonetheless,
      combination NRT has the potential to provide effective treatment of tobacco
      dependence in persons whose dependence is refractory to currently available
      treatments.

PMID- 11524026
TI  - Methylphenidate (OROS formulation).
AB  - Methylphenidate is a CNS stimulant that is thought to block the reuptake of
      dopamine and noradrenaline (norepinephrine) into the presynaptic neuron. A
      sustained release (OROS formulation of the drug has been developed for use in
      children with attention deficit/hyperactivity disorder (ADHD). In children aged 6
      to 12 years with ADHD, the maximum plasma concentration of OROS methylphenidate
      18 to 54 mg was reached after approximately 7 to 8 hours. In adults, the plasma
      concentration-time profile of OROS methylphenidate differed markedly from that of
      the sustained release and immediate release (IR) methylphenidate formulations. In
      a clinical trial involving 282 children with ADHD, once daily OROS
      methylphenidate 18 to 54 mg was significantly more effective than placebo and
      demonstrated an effect similar to IR methylphenidate 5 to 15 mg 3 times daily in
      reducing the symptoms of ADHD. OROS methylphenidate demonstrated sustained
      efficacy in a 1-year noncomparative study involving children with ADHD. In
      clinical trials, the OROS formulation of methylphenidate had a tolerability
      profile similar to that of IR methylphenidate.

PMID- 11524030
TI  - When should triptans be taken during a migraine attack?
AB  - The common strategy to treat a migraine attack as soon as it begins, made for
      classical acute antimigraine treatments such as ergotamine and analgesics, has
      not been transposed to the triptans. The recommendation to delay triptan intake
      until headache intensity is at least moderate is merely a habit generated by the
      protocol used in triptan trials and a nonvalidated attempt to reduce costs. It is
      also favoured by the few studies suggesting that sumatriptan is less effective
      when given early in an attack, especially during the aura phase. Recent
      retrospective analyses of small numbers of 'protocol violators' in controlled
      trials of sumatriptan suggest that the drug is more efficient when taken while
      the headache is mild. Pain-free responses and therapeutic gains over aspirin
      (acetylsalicylic acid)-metoclopramide or ergotamine-caffeine combinations were
      increased under these conditions. The available circumstantial evidence is
      reviewed and discussed. Before any conclusion can be drawn and recommendation
      made, results are awaited from randomised controlled trials specifically
      addressing whether or not triptans are more efficient in mild headache.
      Meanwhile, there seems to be no medical reason to withhold treatment of a mild
      headache with a triptan as long as triptan intake does not exceed 1 or 2 doses
      per week. Most mild headaches in patients with migraine appear indeed to be mild
      migraine attacks, even when the headache characteristics are those of tension
      type headache.

PMID- 11524025
TI  - Smoking in patients receiving psychotropic medications: a pharmacokinetic
      perspective.
AB  - Many psychiatric patients smoke, and are believed to be heavier smokers than
      those without psychiatric disorders. Cigarette smoking is one of the
      environmental factors that contributes to interindividual variations in response
      to an administered drug. Polycyclic aromatic hydrocarbons (PAHs) present in
      cigarette smoke induce hepatic aryl hydrocarbon hydroxylases, thereby increasing
      metabolic clearance of drugs that are substrates for these enzymes. PAHs have
      been shown to induce 3 hepatic cytochrome P450 (CYP) isozymes, primarily CYP1A1,
      1A2 and 2E1. Drug therapy can also be affected pharmacodynamically by nicotine.
      The most common effect of smoking on drug disposition in humans is an increase in
      biotransformation rate, consistent with induction of drug-metabolising enzymes.
      Induction of hepatic enzymes has been shown to increase the metabolism and to
      decrease the plasma concentrations of imipramine, clomipramine, fluvoxamine and
      trazodone. The effect of smoking on the plasma concentrations of amitriptyline
      and nortriptyline is variable. Amfebutamone (bupropion) does not appear to be
      affected by cigarette smoking. Smoking is associated with increased clearance of
      tiotixene, fluphenazine, haloperidol and olanzapine. Plasma concentrations of
      chlorpromazine and clozapine are reduced by cigarette smoking. Clinically,
      reduced drowsiness in smokers receiving chlorpromazine, and benzodiazepines,
      compared with nonsmokers has been reported. Increased clearance of the
      benzodiazepines alprazolam, lorazepam, oxazepam, diazepam and demethyl-diazepam
      is found in cigarette smokers, whereas chlordiazepoxide does not appear to be
      affected by smoking. Carbamazepine appears to be minimally affected by cigarette
      smoke, perhaps because hepatic enzymes are already stimulated by its own
      autoinductive properties. Cigarette smoking can affect the pharmacokinetic and
      pharmacodynamic properties of many psychotropic drugs. Clinicians should consider
      smoking as an important factor in the disposition of these drugs.

PMID- 11524031
TI  - Do statins afford neuroprotection in patients with cerebral ischaemia and stroke?
AB  - An emerging body of evidence indicates that beta-hydroxy-beta-methylglutaryl
      coenzyme A (HMG-CoA) reductase inhibitors, or 'statins', provide neuroprotection
      in addition to reducing ischaemic stroke. Statins reduce the incidence of
      ischaemic stroke by stabilising atherosclerotic plaques in the precerebral
      vasculature and through antithrombotic actions, and the neuroprotective effects
      of statins may confer significant clinical benefit. Some of these neuroprotective
      effects are likely to be cholesterol independent and mediated by the interruption
      of isoprenoid biosynthesis. Therapy with statins may modulate endothelial
      function and preserve blood flow to regions exposed to an ischaemic insult. In
      particular, statin-mediated preservation of endothelial nitric oxide synthase
      activity in cerebral vasculature, especially in the ischaemic penumbra, may limit
      neurological deficit. Moreover, putative anti-inflammatory and antioxidant
      properties of statins may confer additional neuroprotection. Further large
      clinical trials are necessary to address the role of statin therapy in the
      primary prevention of stroke, small vessel cerebrovascular disease and vascular
      dementia.

PMID- 11524032
TI  - CNS involvement in primary Sjogren's syndrome: prevalence, clinical aspects,
      diagnostic assessment and therapeutic approach.
AB  - Among the systemic manifestations of primary Sjogren's syndrome, neurological
      involvement is still an intriguing and debated issue. Although peripheral nervous
      system abnormalities are a well documented occurrence with a reported prevalence
      ranging from 10 to 20%, opinions differ as to the prevalence of CNS disease, with
      suggestions from 'nonexistent' to 'very common'. The lack of agreement probably
      reflects the different populations selected, different inclusion criteria and
      lack of rigorous epidemiological studies. In our experience, CNS involvement was
      detected in 7 of 87 (8%) unselected consecutive patients observed over a period
      of 5 years. The spectrum of CNS involvement is wide, including focal, diffuse,
      neuropsychiatric and spinal cord symptoms, frequently characterised by insidious
      onset, remitting course and, sometimes, progressive evolution. The diagnostic
      approach enabling early recognition of this complication relies on careful
      clinical assessment using history and physical examination combined with
      neuropsychological testing and instrumental, laboratory and imaging
      investigations such as magnetic resonance imaging, single photon emission
      computed tomography, electrophysiological testing and CSF analysis. The clinical
      picture often shows spontaneous remission, but when overt neurological symptoms
      occur or become progressive, therapeutic interventions with high dose
      corticosteroids and cytotoxic agents, such as intravenous cyclophosphamide pulse
      therapy, may be indicated.

PMID- 11524033
TI  - Harnessing the clinical potential of antiepileptic drug therapy: dosage
      optimisation.
AB  - For patients with epilepsy, effective seizure control is the most important
      determinant of good quality of life. To achieve this, antiepileptic drug (AED)
      dosages should be individualised to maximise therapeutic benefit and to avoid
      most--if not all--adverse effects. Several studies suggest that, in routine
      clinical practice, dosage individualisation is often suboptimal. This may lead to
      patients receiving unnecessarily large dosages. Conversely, it may lead to
      patients switching to an alternative therapy (when clinical response is deemed
      insufficient), without exploration of the full dosage range. Indeed, dosage
      optimisation--which should involve consideration of the treatment setting and
      individual patient characteristics--can be a complicated process requiring skill
      and patience. In general neurological practice, most AEDs should be started at a
      low dosage and gradually titrated upwards. Starting dosages are similar in most
      types of epilepsy; however, if a rapid onset of therapeutic action is required,
      phenytoin, phenobarbital (phenobarbitone), levetiracetam and gabapentin are
      probably the best tolerated AEDs for starting at full dosage. The initial target
      maintenance dosage of an AED should be based on the dose-response profile of the
      drug, and on specific patient characteristics. Usually, the lowest effective
      daily dose expected to provide seizure control should be used, although various
      factors (e.g. stage and severity of epilepsy, pharmacokinetic and pharmacodynamic
      considerations, attitude of the patient) will markedly influence dosage
      selection. If seizures are not controlled on the initial target dose, the dosage
      should be increased gradually until complete seizure control is achieved or
      intolerable adverse effects occur. In most patients who fail to respond to the
      initially prescribed drug, switching to another AED (monotherapy) is the best
      option. Combination therapy may be appropriate for patients unresponsive to 2 or
      more sequential monotherapies. Therapeutic drug monitoring (measurement of serum
      drug concentrations) is useful in various settings, such as when drug
      interactions are expected, toxicity is suspected, or when AEDs with nonlinear
      pharmacokinetics (e.g. phenytoin, carbamazepine) are used. No indications
      currently exist for routine therapeutic drug monitoring of the newer AEDs. In
      summary, dosage regimens of AEDs should be assessed regularly, and adjusted if
      necessary, so that patients can derive optimal therapeutic benefit. For patients
      considered 'difficult to treat' (i.e. those in whom seizures remain incompletely
      controlled after several attempts at treatment), referral to a specialist is
      recommended.

PMID- 11524034
TI  - Secondary prevention of stroke in patients with nonvalvular atrial fibrillation:
      optimal intensity of anticoagulation.
AB  - Nonvalvular atrial fibrillation (NVAF) is frequently seen in elderly people and
      has become a main cause of cardioembolic stroke. The efficacy of anticoagulation
      for primary prevention of stroke or transient ischaemic attacks (TIAs) in
      patients with NVAF has been established by prospective, randomised and controlled
      trials. Warfarin decreased the frequency of all strokes by 68% and the rate of
      the combined outcome of stroke, systemic embolism or death by 48%.
      Anticoagulation with warfarin using international normalised ratios (INRs)
      ranging from 2.0 to 3.0 is recommended for patients with NVAF, who have any of
      the risk factors identified by the Atrial Fibrillation Investigators (AFI)
      [previous stroke or TIA, history of hypertension, diabetes mellitus, advanced age
      (> or = 65 years old), congestive heart failure and coronary artery disease], the
      American College of Chest Physicians (ACCP) [increased age (> 75 years old),
      prior stroke, hypertension and heart failure], or the Stroke Prevention in Atrial
      Fibrillation (SPAF) investigators [women > 75 years old, prior stroke, systolic
      blood pressure > 160mm Hg, recent heart failure, and fractional shortening < 25%
      on echocardiography]. For the secondary prevention of stroke, the efficacy of
      adjusted-dose warfarin therapy has been demonstrated by 2 major randomised
      trials. SPAF III (INR 2.0 to 3.0) demonstrated a lower incidence of ischaemic
      stroke or systemic embolism (3.4 %/year) compared with low fixed-dose warfarin
      plus aspirin (acetylsalicylic acid) [11.9%]. The European Atrial Fibrillation
      Trial [EAFT] (INR 2.5 to 4.0) showed a lower incidence of all stroke (4.0 %/year)
      with adjusted-dose warfarin compared with placebo (12.0 %/year). The incidence of
      major bleeding in the adjusted-dose warfarin group in SPAF III and EAFT was 2.4
      and 2.8 %/year, respectively. EAFT incidence rates for the occurrence of a first
      ischaemic or haemorrhagic complication analysed by INR range indicated that the
      rate was lowest at INRs of 2.0 to 2.9, and higher with INRs of 3.0 to 3.9.
      Therefore, the optimal intensity of anticoagulation for prevention of recurrent
      stroke seems to be an INR of between 2.0 and 3.0, as for primary prevention.
      Retrospective and prospective studies from Japan reported that in the elderly,
      haemorrhagic complications occur frequently with INRs above 2.6 and major
      ischaemic events cannot be prevented at INRs below 1.6. Therefore, an INR target
      between 1.6 and 2.6 may be an alternative for secondary prevention of stroke in
      elderly patients with NVAF who have a potential risk of bleeding, to avoid both
      major ischaemic and haemorrhagic events. Antiplatelets may be administered in
      patients who are unable to manage taking warfarin properly or who have a high
      risk of falling and subsequently sustaining a head injury, although the efficacy
      of antiplatelets for secondary prevention of stroke in NVAF has not yet been
      established.

PMID- 11524035
TI  - Adverse effects of antiepileptic drugs on bone structure: epidemiology,
      mechanisms and therapeutic implications.
AB  - Antiepileptic drugs (AEDs) were first associated with disorders of bone in both
      adults and children in the late 1960s. The most severe manifestations of these
      disorders are osteopenia/osteoporosis, osteomalacia and fractures. Bone disease
      has been described in several groups of patients receiving AEDs. Groups
      identified as being more vulnerable to AED-associated bone disease include
      institutionalised patients, postmenopausal women, older men and children.
      Radiological and histological evidence of bone disease is found in patients
      taking AEDs. Numerous biochemical abnormalities of bone metabolism have also been
      described. The severity of bone and biochemical abnormalities is thought to
      correlate with the duration of AED exposure and the number of AEDs used. In
      monotherapy, the AEDs most commonly associated with altered bone metabolism are
      phenytoin, primidone and phenobarbital (phenobarbitone). To date there have been
      no reports of altered bone metabolism in individuals receiving the newer
      anticonvulsants (specifically lamotrigine, topiramate, vigabatrin and
      gabapentin). The mechanisms of AED-associated bone disease are not clearly
      elucidated; however, several theories have been proposed to explain the link. No
      definitive guidelines for evaluation or treatment have yet been determined.

PMID- 11524037
TI  - Influence of beta1-adrenoceptor blockade on the gene expression of adenylate
      cyclase subtypes and beta-adrenoceptor kinase in human atrium.
AB  - There is accumulating evidence of cross-regulation between stimulatory G-protein
      (G(s))-coupled receptors in human atrium. Chronic beta(1)-adrenoceptor antagonist
      treatment can sensitize beta(2)-adrenoreceptors, 5-HT(4) receptors, histamine
      H(2) receptors and possibly beta(4)-adrenoreceptors. To investigate the mechanism
      of such cross-talk between G(s)-coupled receptors, we have measured the mRNA
      expression of the cardiac adenylate cyclases (types IV, V, VI and VII) and of
      beta-adrenoceptor kinase 1 in human atria using TaqMan quantitative PCR, and
      compared expression between patients chronically receiving a beta(1)-adrenoceptor
      antagonist and non-treated patients. The results showed no difference in gene
      expression between the two groups of patients; however, significant positive
      correlations of gene expression between adenylate cyclase subtypes were found. We
      conclude that beta(1)-adrenoceptor antagonists do not change the absolute levels
      of gene expression of adenylate cyclase subtypes in human atrium. The co-ordinate
      regulation among adenylate cyclase subtypes and the influence of beta(1)
      adrenoceptor antagonists need to be investigated further.

PMID- 11524036
TI  - Venlafaxine extended-release: a review of its use in the management of major
      depression.
AB  - Venlafaxine inhibits presynaptic reuptake of serotonin (5-hydroxytryptamine; 5
      HT) and noradrenaline (norepinephrine). Venlafaxine extended-release (XR) has
      been investigated in patients with major depression and in patients with major
      depression with associated anxiety in randomised, double-blind, multicentre
      trials. A therapeutic response in patients with major depression was evident at
      week 2 of treatment with venlafaxine XR 75 to 225 mg/day in a placebo-controlled
      trial. By week 4, the drug was significantly more effective than placebo at
      reducing both the Hamilton Rating Scale for Depression (HAM-D) and Montgomery
      Asberg Depression Rating Scale (MADRS) total scores. Furthermore, cumulative
      relapse rates were lower among recipients of venlafaxine XR 75 to 225 mg/day than
      placebo recipients after 3 and 6 months in another trial. Venlafaxine XR 75 to
      150 mg/day was significantly more effective than venlafaxine immediate-release
      (IR) 75 to 150 mg/day or placebo during a 12-week study. Reductions from baseline
      in all 4 efficacy parameters (HAM-D, MADRS, HAM-D depressed mood item and the
      Clinical Global Impression Severity of Illness scale) were significantly higher
      among patients treated with venlafaxine XR than venlafaxine IR or placebo at week
      12 (using an intent-to-treat, last observation carried forward analysis).
      Venlafaxine XR 75 to 225 mg/day was compared with fluoxetine 20 to 60 mg/day in
      patients with major depression in 2 randomised, double-blind, placebo-controlled,
      multicentre studies. Remission rates were significantly in favour of venlafaxine
      XR recipients in one study: 37, 22 and 18% of patients treated with venlafaxine
      XR, fluoxetine or placebo, respectively, achieved full remission (HAM-D total
      score < or = 7 at end-point). In the other trial, venlafaxine XR and fluoxetine
      had comparable efficacy in reducing HAM-D and Hamilton Rating Scale for Anxiety
      (HAM-A) total scores compared with placebo. However, the HAM-A response rate was
      significantly higher with venlafaxine XR than with fluoxetine at week 12. In a
      comparative study involving paroxetine, reductions from baseline in HAM-D and
      MADRS total scores in patients given venlafaxine XR 75 mg/day or paroxetine 20
      mg/day for 12 weeks were significant, but no significant differences between
      treatment groups were evident. Discontinuation rates because of unsatisfactory
      clinical response were similar among patients treated with venlafaxine XR,
      fluoxetine or paroxetine. Adverse events pertaining to the digestive (nausea, dry
      mouth), nervous (dizziness, somnolence, insomnia) and urogenital (abnormal
      ejaculation) systems as well as sweating were the most frequently reported
      adverse events during 8 to 12 weeks of treatment in 3 randomised, double-blind,
      multicentre trials. Comparative studies with fluoxetine and paroxetine
      demonstrated a similar adverse event profile to venlafaxine XR. CONCLUSION:
      Venlafaxine XR has shown efficacy in the treatment of major depression and was at
      least as effective as fluoxetine or paroxetine and more effective than
      venlafaxine IR. Furthermore, it is effective at reducing symptoms of anxiety in
      depressed patients. The incidence of adverse events in recipients of venlafaxine
      XR is similar to that in patients receiving treatment with well established
      selective serotonin reuptake inhibitors. As an effective and well tolerated
      antidepressant, venlafaxine XR should be considered as a first-line
      pharmacological treatment in patients with major depression.

PMID- 11524038
TI  - Beneficial effect of beta-adrenergic blockade on left ventricular function in
      haemodialysis patients.
AB  - Congestive heart failure is a common and serious complication in patients
      undergoing chronic dialysis. However, there have been no studies on preferential
      medical therapies to improve left ventricular function in haemodialysis patients.
      Beta-blocker treatment is known to improve left ventricular function in patients
      with dilated cardiomyopathy; moreover, plasma levels of noradrenaline and
      natriuretic peptides are sensitive markers of left ventricular dysfunction. The
      present study investigated whether beta-blocker treatment could improve left
      ventricular function in haemodialysis patients with a dilated left ventricle. Our
      study group comprised 14 haemodialysis patients with a dilated left ventricle,
      who had undergone maintenance haemodialysis for a mean of 11 years. The following
      haemodynamic parameters were evaluated before and after 4 months of treatment
      with the beta-blocker metoprolol: left ventricular dimension at end-systole and
      end-diastole, and fractional shortening. Plasma levels of noradrenaline, atrial
      natriuretic peptide and brain natriuretic peptide were also determined. Dry body
      weight and haemoglobin concentration showed no significant change after compared
      with before treatment with metoprolol. Heart rate decreased significantly, from
      79+/-9 beats/min to 69+/-9 beats/min, but systolic blood pressure remained
      unchanged. The left ventricular dimension both at end-systole and at end-diastole
      was decreased, and fractional shortening increased significantly. Plasma levels
      of noradrenaline did not change significantly, but those of atrial natriuretic
      peptide and brain natriuretic peptide decreased markedly [from 100+/-89 pg/ml to
      46+/-29 pg/ml (P=0.0051) and from 549+/-516 pg/ml to 140+/-128 pg/ml (P=0.0035)
      respectively]. In conclusion, beta-blocker therapy with metoprolol can markedly
      attenuate left ventricular remodelling and decrease the plasma levels of
      natriuretic peptides in haemodialysis patients with a dilated left ventricle.

PMID- 11524039
TI  - Post-load glucose measurements in oral glucose tolerance tests correlate well
      with 1,5-anhydroglucitol, an indicator of overall glycaemic state, in subjects
      with impaired glucose tolerance.
AB  - Using both cross-sectional and longitudinal methods, we investigated the
      relationship between post-load serum glucose concentration in a 75 g oral glucose
      tolerance test (OGTT) and overall glycaemic state in subjects with impaired
      glucose tolerance (IGT). Glycaemic state was assessed by measuring glycated
      haemoglobin (HbA1c) and the serum concentration of 1,5-anhydroglucitol (1,5-AG).
      In the cross-sectional study, the concentration of 1,5-AG, while remaining within
      a normal range, was reduced to a degree proportional to the post-load glycaemic
      level. Although the correlation between HbA1c and post-load plasma glucose was
      relatively weak (r=0.281, P<0.001), a significant inverse correlation (r=-0.824,
      P<0.0001) was found between 1,5-AG and mean post-load plasma glucose
      concentration in 211 subjects with IGT. Fasting plasma glucose (r=-0.539,
      P<0.0001) and 2 h plasma glucose (r=-0.621, P<0.0001) were correlated with 1,5-AG
      less strongly than was post-load glycaemia. Both 1,5-AG and HbA1c were correlated
      weakly but significantly with the fasting insulin concentration. In the
      longitudinal study we measured 1,5-AG and mean post-load plasma glucose with an
      OGTT once yearly for 10 years in 15 subjects with IGT. Strong inverse
      correlations were seen between 1,5-AG and mean post-load plasma glucose in each
      subject (range of r values among subjects of -0.584 to -0.978). These findings
      suggest a close relationship between post-load plasma glucose concentration
      measured by OGTT and overall glycaemic state in subjects with IGT.

PMID- 11524040
TI  - Increased DNA oxidative susceptibility without increased plasma LDL oxidizability
      in Type II diabetes: effects of alpha-tocopherol supplementation.
AB  - In vivo supplementation studies of the antioxidant alpha-tocopherol in human Type
      II diabetes have used surrogate, rather than direct, markers of oxidative
      damage/antioxidant protection and have used higher doses of alpha-tocopherol than
      used in coronary secondary prevention trials. We tested the hypothesis that oral
      alpha-tocopherol in a dosage regimen used in secondary prevention trials would
      reduce directly observed oxidatively induced single-strand breaks in lymphocyte
      DNA in Type II diabetes. We studied 40 people with Type II diabetes and 30
      controls in a randomized, double-blind, placebo-controlled trial of 400 i.u. of
      oral alpha-tocopherol daily for 8 weeks. Lymphocyte DNA single-strand breaks and
      low-density lipoprotein (LDL) particle size and oxidizability were measured at
      baseline, after 8 weeks, and after 4 weeks washout. Polymorphisms in the gene for
      the antioxidant enzyme paraoxonase-1 gene (position 192) were measured. The
      diabetics had increased DNA oxidative susceptibility (P=0.008), without increased
      LDL oxidative susceptibility. There was a direct relationship between DNA
      oxidative susceptibility and baseline plasma alpha-tocopherol in the diabetes
      group alone (r=0.421, r(2)=0.177 and P=0.023), but DNA and LDL oxidative
      susceptibility were not influenced by alpha-tocopherol supplementation in either
      group in this regimen. Paraoxonase-1 gene polymorphisms did not contribute to LDL
      or DNA oxidative susceptibility or response to alpha-tocopherol. Increased DNA
      oxidative susceptibility, therefore, can occur in Type II diabetes without
      increased LDL oxidative susceptibility, but alpha-tocopherol supplementation in
      this regimen has no influence on DNA or LDL oxidative susceptibility in Type II
      diabetes or controls. Polymorphisms in the paraoxonase gene (position 192) are
      not associated with differences in oxidative susceptibility or responses to alpha
      tocopherol.

PMID- 11524041
TI  - Importance of glycolytically derived ATP for Na+ loading via Na+/H+ exchange
      during metabolic inhibition in guinea pig ventricular myocytes.
AB  - The increase in the intracellular Na+ concentration ([Na+](i)) during myocardial
      ischaemia is crucial for ischaemia/reperfusion cell injury, and the cardiac
      subtype of the Na+/H+ exchanger (NHE-1) has been shown to be a major pathway for
      Na(+) loading. While the importance of glycolytically derived ATP for the optimal
      functioning of membrane transporters and channels has been suggested, whether NHE
      1 is actually activated during myocardial ischaemia remains controversial. Here
      we examined whether the activity of NHE-1 is predominantly dependent on
      intracellular ATP generated by glycolysis, and whether the additional inhibition
      of glycolysis can affect the increase in ([Na+](i)) during the inhibition of
      oxidative phosphorylation in intact guinea pig ventricular myocytes. The
      selective inhibition of glycolysis by 2-deoxyglucose prevented the recovery of
      intracellular pH and the transient increase in ([Na+](i)) following intracellular
      acidosis induced by a NH(4)Cl pre-pulse. During severe metabolic inhibition (SMI;
      induced by amobarbital and carbonyl cyanide m-chlorophenylhydrazone in a glucose
      free perfusate), most myocytes changed from rod-shaped to contracted forms by
      approximately 15 min. ([Na+](i)) increased linearly until rigor contracture
      occurred, but after rigor contracture the rate of increase was blunted. The
      increase in ([Na+](i)) during SMI was suppressed significantly by an inhibitor of
      NHE-1, hexamethylene amiloride. The increase in the intracellular Mg(2+)
      concentration, which can reciprocally indicate depletion of intracellular ATP,
      was small during the initial 10 min of SMI, but became larger from just a few
      minutes before rigor contracture. In the presence of 2-deoxyglucose, the time to
      rigor during SMI was shortened, but the increase in ([Na+](i)) before rigor
      contracture was not significant, and was much less than that in the absence of 2
      deoxyglucose. It is concluded that ATP generated by glycolysis is essential to
      activate NHE-1, and that the dependence of NHE-1 on glycolysis might affect the
      increase in ([Na+](i)) observed during myocardial ischaemia.

PMID- 11524042
TI  - Mechanics of the carotid artery wall and baroreflex sensitivity after acute
      ethanol administration in young healthy volunteers.
AB  - The effects of ethanol administered orally (300 mg/kg in 250 ml of water) or
      intravenously (7.5 mg.min(-1).kg(-1) in 250 ml of saline over 40 min) on common
      carotid haemodynamics, wall mechanics and baroreflex sensitivity were compared
      with the effects of the intravenous infusion of 250 ml of saline. Ethanol or
      saline was administered to 10 healthy volunteers after 30 min of supine rest, and
      measurements were obtained 40 min (median; range 34-46 min) after administration.
      After ethanol administration, the plasma alcohol level rose from 0 to 0.3+/-0.07
      g/l. Mean arterial blood pressure had risen slightly at 20 min, but was
      normalized by 40 min, the time at which the haemodynamic study was performed.
      Heart rate decreased after infusion of either saline or alcohol, but was
      unchanged after oral ethanol administration. Both oral and intravenous ethanol
      administration were associated with significant decreases in baroreflex
      sensitivity, carotid shear stress and blood velocity, compared with resting
      values, while the mean carotid artery diameter was increased, and blood viscosity
      and mean blood flow were unchanged. No changes were observed in these parameters
      after saline administration. Ethanol, administered either intravenously or
      orally, increased the stiffness of the carotid artery and decreased the
      pulsatility (systo-diastolic changes) of its diameter. A direct, statistically
      significant correlation was found between the decrease in shear stress and the
      decrease in baroreflex heart rate control sensitivity after both modes of alcohol
      administration, while no such correlation was found between the increase in the
      Peterson elastic modulus and the decrease in carotid diameter pulsatility on the
      one hand or the decrease in baroreflex sensitivity on the other. In conclusion,
      reduced shear stress associated with vasodilatation of the carotid artery wall
      may contribute to the decrease in baroreflex sensitivity observed after acute
      ethanol administration.

PMID- 11524043
TI  - Peripheral vascular and nerve function associated with lower limb amputation in
      people with and without diabetes.
AB  - Multiple factors, including peripheral vascular disease and neuropathy,
      contribute to the development and perpetuation of complications of the lower
      extremities in diabetes. The main aim of the present study was to assess the
      peripheral vascular and nerve status of diabetic and non-diabetic subjects that
      had undergone lower limb amputation. Various non-invasive tests of peripheral
      vascular and nerve function were carried out on subjects who had undergone
      unilateral lower limb amputation and were now attending a Rehabilitation Centre.
      The control group (n=23), the diabetic amputee group (n=64) and the non-diabetic
      amputee group (n=32) were age-matched. Only the diabetic amputee group had
      evidence of medial arterial calcification. Transcutaneous oxygen levels were
      significantly lower in the diabetic amputee group (median 43 mmHg; interquartile
      range 33-49 mmHg) than in the control (59; 56-74 mmHg) and non-diabetic amputee
      (57; 43-65 mmHg) groups (control compared with diabetic amputee group, P<0.001;
      diabetic amputee compared with non-diabetic amputee group, P<0.01). The same
      trend was found for carbon dioxide levels in the skin [mmHg: diabetic amputees,
      25 (21-37); controls, 38 (32-42); non-diabetic amputee, 34 (31-39)] (control
      compared with diabetic amputee, P<0.01; diabetic amputee compared with non
      diabetic amputee, P<0.05). Vibration and pressure perception measurements (which
      assess Abeta nerve fibre function) showed that both the diabetic amputee and non
      diabetic amputee subjects had significantly greater impairment than the controls.
      However, measures of Aalpha and C nerve fibre function were abnormal only in the
      diabetic amputee group. Thus the peripheral vascular and nerve functions of age
      matched diabetic and non-diabetic subjects having undergone lower limb amputation
      show specific differences, with non-diabetic amputees exhibiting signs of
      neuropathy. This indicates that factors characteristic of diabetes (such as
      hyperglycaemia and non-enzymic glycation) are associated with calcification,
      lower oxygen and carbon dioxide levels in the skin, and abnormal Aalpha and C
      nerve fibre function.

PMID- 11524044
TI  - Effects of extracellular pH on tumour necrosis factor-alpha production by
      resident alveolar macrophages.
AB  - Cellular acid-base status has been found to exert selective actions on the
      effector functions of activated macrophages (mphi). We examined the effects of
      extracellular pH (pH(o)) on the production of tumour necrosis factor-alpha (TNF
      alpha) induced by lipopolysaccharide (LPS) in resident alveolar mphi. Cells were
      obtained by bronchoalveolar lavage of rabbits, activated in vitro with LPS, and
      cultured at pH(o) 5.5, 6.5 or 7.4 for up to 18 h. The relative abundance of TNF
      alpha mRNA peaked at approximately 2 h. The peak transcript abundance was
      increased at lower pH(o) values. This finding probably reflected pre
      transcription/transcription effects of pH, in as much as the stability of TNF
      alpha mRNA induced with phorbol ester was unaffected by the experimental pH(o)
      values. TNF-alpha secretion by LPS-treated mphi decreased at lower pH(o) values.
      The TNF-alpha content of mphi-conditioned media decreased progressively with
      decrements in pH(o). The reduced TNF-alpha secretion at pH(o) 5.5 was accompanied
      by an increase in the cytosolic TNF-alpha content (compared with that at pH(o)
      7.4), indicating that pH(o) altered TNF-alpha secretion due, in part, to the
      intracellular retention of synthesized cytokine (i.e. a post-translation effect).
      The data show that pH(o) has multiple effects (pre-transcription/transcription
      and post-translation) on TNF-alpha production induced by LPS in resident alveolar
      mphi. These results suggest that the role of alveolar mphi in inflammatory
      responses is modulated by pH(o), which may be important in tumours/abscesses and
      sites of infection where the external milieu is acidic.

PMID- 11524045
TI  - Interactions between nitric oxide and renal nerves in the excretion of a saline
      load in obese Zucker rats.
AB  - The present study investigated the potential role of nitric oxide (NO) and its
      interaction with renal sympathetic nerves in modulating the excretory responses
      to an acute saline volume expansion (VE), of 10% of body weight, in the
      innervated and denervated kidneys of both lean and obese Zucker rats. This was
      done using the NO synthase inhibitors N(G)-nitro-L-arginine methyl ester (L
      NAME), 7-nitroindazole and aminoguanidine. In lean rats, cumulative urinary
      sodium excretion (cuU(Na)V) after 40 min of VE in the innervated kidney was
      enhanced by 48% in L-NAME-treated rats compared with that in untreated rats, but
      this was not the case for the denervated kidney. VE in untreated obese rats
      raised cuU(Na)V to a lesser extent than in the untreated lean rats, by 36% and
      46% in the denervated and innervated kidneys respectively (both P<0.001). L-NAME
      treatment of obese rats increased cuU(Na)V after VE compared with that in
      untreated obese rats, by 48% in the denervated kidney and by 136% in the
      innervated kidney (both P<0.001). The magnitude of cuU(Na)V after VE in both
      kidneys of 7-nitroindazole-treated obese rats was not different from that in
      untreated obese rats. However, cuU(Na)V was raised (P<0.01) by 56% in the
      innervated, but not the denervated, kidney of aminoguanidine-treated obese rats.
      These data show that NO is partially involved in mediating the reflex renal
      responses to VE in Zucker rat strains. NO, possibly generated by endothelial NO
      synthase, exerts its effects in obese rats through a renal-nerve-independent
      mechanism, while the effect of NO generated by inducible NO synthase requires
      intact renal innervation.

PMID- 11524046
TI  - Cytokine up-regulation in ischaemic/reperfused lungs perfused with University of
      Wisconsin solution and normal saline.
AB  - Ischaemia/reperfusion (I/R) lung injury using University of Wisconsin solution
      (UW) as perfusate has not been well studied. Isolated rat lungs were challenged
      with various periods of ischaemia and/or reperfusion. Haemodynamics, lung weight
      gain (LWG), capillary filtration coefficient (K(fc)), tissue pathology, the
      concentrations of cytokines in the perfusate, and mRNAs for the various cytokines
      in the lung tissues were measured. I/R induced a permeability type of pulmonary
      oedema, as reflected by increases in LWG and K(fc). LWG and K(fc) in the
      I(45)R(60)(UW) group (45 min of ischaemia followed by 60 min of reperfusion with
      UW) were only 2% and 5% respectively of those in the I(45)R(60)(NS) group (where
      NS is normal saline). LWG and K(fc) in the UW group had both increased by 180
      min, to values similar to those in the I(45)R(60)(NS) group. However, these
      findings show that UW was remarkably effective at preventing LWG after 60 min of
      reperfusion, and was more than 3-fold more effective than NS in delaying LWG. For
      longer ischaemic times only, or the same period of ischaemia followed by longer
      reperfusion periods, greater lung injury occurred. I/R lung injury also induced
      increased concentrations of tumour necrosis factor-alpha (TNF-alpha), interleukin
      1 and interleukin 6 in the perfusate, and increased the mRNAs for these cytokines
      in lung tissue. A significant correlation was obtained between TNF-alpha
      concentration and LWG. TNF-alpha production in the I(45)R(60)(UW) group was only
      7% of that in the I(45)R(60)(NS) group. However, TNF-alpha mRNA expression in the
      I(45)R(60)(UW) group was 80% of that in the I(45)R(60)(NS) group. This indicates
      that transcription/translation do not correlate well with cytokine production,
      and also suggests that one reason for the effectiveness of UW in delaying LWG may
      be because it delays TNF-alpha production. In summary, ischaemia or I/R caused a
      permeability-type pulmonary oedema that was associated with leucocyte
      infiltration and the up-regulation of various cytokines, regardless of the
      perfusion fluid. Except for pulmonary hypertension, less severe I/R lung injury
      and delayed cytokine production in lungs perfused with UW, the pattern of injury
      associated with I/R challenge was similar to that in lungs perfused with NS. We
      propose that more or long-acting protective agents are required as additives in
      order to modify UW to produce an optimal preservation solution.

PMID- 11524047
TI  - Sequential changes in in vivo muscle and liver protein synthesis and plasma and
      tissue glutamine levels in sepsis in the rat.
AB  - We have investigated sequential changes in skeletal muscle and hepatic protein
      synthesis following sepsis, and their relationship to changes in circulating and
      tissue glutamine concentrations. Male Wistar rats underwent caecal ligation and
      puncture (CLP) or sham operation, with starvation, and were killed 24, 72 or 96 h
      later. A group of non-operated animals were killed at the time of surgery.
      Protein synthesis was determined using a flooding dose of L-[4-(3)H]
      phenylalanine, and glutamine concentrations were measured by an enzymic
      fluorimetric assay. Protein synthesis in gastrocnemius muscle fell in all groups.
      Gastrocnemius total protein content was reduced after CLP and at 72 and 96 h
      after sham operation. After CLP, protein synthesis was lower at 24 h, and total
      protein content was lower at 72 and 96 h, than in sham-operated animals. CLP was
      associated with increased liver protein synthesis at all time points, whereas
      there was no change after sham operation. Liver protein content did not change
      after CLP, but was lower at 72 and 96 h after sham operation than in non-operated
      animals. Plasma glutamine concentrations were reduced at 24 h after sham
      operation, and at 72 and 96 h after CLP. Muscle glutamine concentrations were
      reduced in all groups, with the decrease being greater following CLP than after
      sham operation. In the liver, glutamine concentrations were unchanged after CLP,
      but increased after sham operation. In rats with sepsis, decreases in muscle
      protein synthesis and content are associated with markedly reduced muscle
      glutamine concentrations. Plasma glutamine concentrations are initially
      maintained, but fall later. In liver, protein synthesis is increased, while
      glutamine concentrations are preserved. These results support a peripheral-to
      splanchnic glutamine flux in sepsis.

PMID- 11524048
TI  - Differential effects of cilostazol and pentoxifylline on vascular endothelial
      growth factor in patients with intermittent claudication.
AB  - Cilostazol is a new phosphodiesterase inhibitor with anti-platelet and
      vasodilatory properties. Cilostazol and pentoxifylline are the only two drugs
      that have been approved for the treatment of patients with intermittent
      claudication. However, the mechanisms by which exercise tolerance is improved
      remain unclear. Vascular endothelial growth factor (VEGF) is a potent endothelial
      mitogen that results in angiogenesis when overexpressed in human subjects. To
      assess the potential role of VEGF in the improvement in exercise tolerance, we
      investigated plasma levels of VEGF in 50 patients with intermittent claudication
      who were allocated randomly to groups receiving cilostazol (n=17), pentoxifylline
      (n=17) or placebo (n=16). Patients given either cilostazol or pentoxifylline
      showed a significant improvements in maximal walking distance compared with the
      placebo group (34 m and 33 m respectively, compared with 5 m; both P<0.05).
      Neither cilostazol nor pentoxifylline increased the ankle-brachial index after
      treatment. Circulating VEGF levels were increased (from 116+/-29 to 169+/-45
      pg/ml; P=0.002), and the levels of VEGF were correlated significantly with
      exercise tolerance in a positive direction (r=0.88, P=0.004), in those patients
      treated with cilostazol that did not have diabetes mellitus. In contrast, VEGF
      levels remained stable after the administration of pentoxifylline. These findings
      suggest that VEGF may contribute to the cilostazol-related improvement in
      exercise tolerance in non-diabetic patients. However, pentoxifylline did not
      affect VEGF levels, although a similar improvement in maximal walking distance
      was achieved. Thus the mechanisms involved in the pentoxifylline-treated group
      were different from those in the cilostazol-treated group, and require further
      study.

PMID- 11524049
TI  - Haemodynamics of the pressor effect of oral water in human sympathetic
      denervation due to autonomic failure.
AB  - Oral water ingestion increases blood pressure in normal elderly subjects and in
      patients suffering from autonomic failure, but the time course of the
      haemodynamic changes is not known. We therefore studied 14 subjects with
      documented sympathetic denervation due to pure autonomic failure, with continuous
      haemodynamic recordings obtained before and after ingestion of 500 ml of
      distilled water at room temperature. The time course of changes in values of
      systolic and diastolic beat-by-beat finger blood pressure, heart rate, stroke
      volume, cardiac output, ejection fraction and total peripheral resistance were
      analysed. Systolic blood pressure rose from 115+/-8 mmHg (mean+/-S.E.M.) to 133+/
      8 mmHg (P<0.001), and diastolic blood pressure from 64+/-4 to 73+/-4 mmHg
      (P<0.001), with the pressor response beginning a few minutes after water
      ingestion, plateauing between 10 and 35 min (peak at 14 min), and returning to
      baseline at 50 min. Heart rate fell from 71+/-2.5 to 67+/-2 beats/min (P<0.001),
      and total peripheral resistance increased from 1.31+/-0.19 to 1.61+/-0.24 m-units
      (P<0.001). There were no significant changes in ejection fraction, stroke volume
      or cardiac output. This study confirmed a pressor response to oral water in
      subjects with sympathetic denervation. The temporal profile of the response did
      not favour reflexly mediated sympathetic activation. As subjects with autonomic
      failure are prone to salt and water depletion, and since blood pressure is
      exquisitely sensitive to such changes, it may be that the observed response is
      due to repletion or restoration of intravascular and extravascular fluid volume.

PMID- 11524050
TI  - Benefits and barriers associated with participation in food programs in three low
      income Ontario communities.
AB  - Our objective was to identify the benefits and barriers associated with
      participation in food programs. We did a content analysis of focus groups with
      parents (n=21), teachers (n=10), project staff (n=21), and children (n=17) in
      three low-income Ontario communities. The key benefits identified by the three
      adult groups were hunger alleviation and social contact opportunities for both
      parents and children. Parents also benefited from volunteering with and/or
      participating in food programs because neighbourhood support networks developed.
      Teachers reported that children who attended breakfast programs became more
      attentive in school. The food programs also provided an opportunity for nutrition
      education. Offering food as part of all community programs (not just those
      designed to increase food availability) encouraged participation and increased
      attendance. Children thought that attending food programs kept them healthy, and
      helped them work harder in school. Parents' pride was the main barrier to
      participation in programs; however, parents who were actively involved in program
      delivery did not feel stigmatized accepting food. To encourage participation,
      nutrition professionals should collaborate with local residents to develop and
      implement community-based food programs.

PMID- 11524051
TI  - Body mass index and the risk of recurrent coronary events following acute
      myocardial infarction.
AB  - Although excess adiposity appears to increase the risk of coronary heart disease
      in the general population, its importance in patients with established coronary
      disease is less defined. We evaluated a population-based inception cohort of
      survivors to hospital discharge following first acute myocardial infarction (AMI)
      (n = 2,541) to assess the association between body mass index (BMI) and the risk
      of recurrent coronary events and to explore the mechanisms for this relation.
      Using Cox proportional-hazards regression, we assessed the risk of recurrent
      coronary events associated with levels of adiposity as defined by BMI and then
      investigated potential mechanisms through which adiposity conferred risk by
      examining how adjustment for diabetes mellitus, systemic hypertension, and
      dyslipidemia affected the association. Forty-one percent of the cohort were
      overweight (BMI 25 to 29.9), and 27.8% were obese (BMI > or =30). After
      adjustment for other risk factors, the risk of recurrent coronary events (n =
      418) increased as BMI increased, especially among those who were obese. Using a
      BMI of 16 to 24.9 as the reference group, for mildly overweight patients (BMI 25
      to 27.4), the relative risk (RR) was 0.93 (95% confidence interval [CI] 0.70 to
      1.24); it was 1.16 for more severe overweight patients (BMI 27.5 to 29.9; 95% CI
      0.87 to 1.55). For patients with class I obesity (BMI 30 to 34.9), the RR was
      1.49 (95% CI 1.12 to 1.98), and for class II to III obesity (BMI > or =35), the
      RR was 1.80 (95% CI 1.30 to 2.48). We estimated that clinical measurements of
      diabetes, hypertension, and dyslipidemia explained approximately 43% of this
      risk. Thus, excess adiposity as measured by BMI was associated with an increased
      risk of recurrent coronary events following AMI, particularly among those who
      were obese.

PMID- 11524052
TI  - Reasons for higher in-hospital mortality >24 hours after percutaneous
      transluminal coronary angioplasty in women compared with men.
AB  - Women have a higher in-hospital mortality rate than men after percutaneous
      transluminal coronary angioplasty (PTCA). To determine reasons for this, we
      analyzed the outcome of PTCA at our institution from 1989 to 1995 for 5,989
      patients (2,101 women). Women were older than men (66.8 +/- 10.9 vs 61.0 +/- 11.2
      years, respectively; p <0.0001) and more likely to have diabetes mellitus,
      hypertension, or a history of congestive heart failure than men. In-laboratory
      complications at the time of PTCA were similar for women and men. During the
      first 24 hours after PTCA, women were more likely than men to become hypotensive
      (0.33% vs 0.08%, p = 0.04) and had a higher rate of vascular injury than men
      (1.6% vs 0.6%, p <0.001). More than 24 hours after the procedure, women had a
      significantly higher mortality rate (1.2% vs 0.52%, p = 0.017), which was no
      longer significantly different after adjustment for age (odds ratio 0.72, 95%
      confidence interval 0.39 to 1.32). Multivariate correlates of death >24 hours
      after PTCA were age, a prior history of congestive heart failure, vascular
      injury, and use of thrombolytic agents. Of those dying >24 hours after the
      procedure, 67% of women suffered a noncardiac-related death compared with only
      10% of men (p <0.001). The noncardiac death rate was 0.8% for women and 0.05% for
      men. These deaths were related to renal failure, vascular complications,
      bleeding, hypotension, and stroke, especially hemorrhagic stroke. In conclusion,
      immediate procedural complications at PTCA were similar for women and men;
      however, mortality was higher for women >24 hours after PTCA and before discharge
      due to a higher rate of noncardiac death.

PMID- 11524053
TI  - Usefulness of serial electrocardiograms for diagnosis of acute myocardial
      infarction.
AB  - The purpose of this study was to determine whether the automated detection of
      acute myocardial infarction (AMI) by utilizing artificial neural networks was
      improved by using a previous electrocardiogram (ECG) in addition to the current
      ECG. A total of 4,691 ECGs were recorded from patients admitted to an emergency
      department due to suspected AMI. Of these, 902 ECGs, in which diagnoses of AMI
      were later confirmed, formed the study group, whereas the remaining 3,789 ECGS
      comprised the control group. For each ECG recorded, a previous ECG of the same
      patient was selected from the clinical electrocardiographic database. Artificial
      neural networks were then programmed to detect AMI based on either the current
      ECG only or on the combination of the previous and the current ECGs. On this
      basis, 3 assessors--a neural network, an experienced cardiologist, and an intern-
      separately classified the ECGs of the test group, with and without access to the
      previous ECG. The detection performance, as measured by the area under the
      receiver operating characteristic curve, showed an increase for all assessors
      with access to previous ECGs. The neural network improved from 0.85 to 0.88 (p =
      0.02), the cardiologist from 0.79 to 0.81 (p = 0.36), and the intern from 0.71 to
      0.78 (p <0.001). Thus, the performance of a neural network, detecting AMI in an
      ECG, is improved when a previous ECG is used as an additional input.

PMID- 11524054
TI  - An anti-CD11/CD18 monoclonal antibody in patients with acute myocardial
      infarction having percutaneous transluminal coronary angioplasty (the FESTIVAL
      study).
AB  - Maximal benefits of coronary reperfusion after acute myocardial infarction (AMI)
      with ST-segment elevation may be attenuated by neutrophil-mediated reperfusion
      injury. Inflammatory mediators released from potentially viable myocytes cause
      activation of neutrophils, which traverse the endothelium and enter the
      myocardium. This process involves interaction between the neutrophil-expressed
      CD11/CD18 and endothelial-expressed intercellular adhesion molecule-1 (ICAM-1).
      Preclinical studies have shown that monoclonal antibodies (MAb) to CD18 can limit
      infarct size and preserve left ventricular function. We sought to determine the
      initial clinical safety and tolerability of Hu23F2G (LeukArrest), a humanized MAb
      to CD11/CD18, in patients with AMI who underwent percutaneous transluminal
      coronary angioplasty (PTCA). Sixty patients with AMI were randomized to low- (0.3
      mg/kg) or high-dose (1.0 mg/kg) Hu23F2G or to placebo immediately before PTCA. We
      found no clinically significant differences in vital signs, physical examination,
      laboratory evaluation, or need for subsequent cardiac interventions. In Hu23F2G
      treatment groups, serum concentration of Hu23F2G increased rapidly to 3,234 +/-
      1,298 microg/L (low-dose group) and 15,558 +/- 4409 microg/L (high-dose group)
      between 5 and 60 minutes, then declined over 72 hours to near-baseline values.
      Myocardial single-photon emission computed tomographic imaging 120 to 260 hours
      after PTCA showed no statistically significant differences in final left
      ventricular defect size. Hu23F2G was well tolerated, with no increase in adverse
      events, including infections. Thus, Hu23F2G appears safe and well tolerated in
      patients undergoing PTCA for AMI.

PMID- 11524055
TI  - A risk score system for predicting adverse outcomes and magnitude of benefit with
      glycoprotein IIb/IIIa inhibitor therapy in patients with unstable angina
      pectoris.
AB  - Clinical outcomes of patients with unstable angina are variable. We sought to
      identify predictors of adverse clinical outcomes in patients with unstable angina
      and to investigate whether these factors would predict the magnitude of benefit
      achieved with platelet glycoprotein IIb/IIIa inhibition. We analyzed 20 variables
      in the 1,915 patients enrolled in the Platelet Receptor Inhibition for Ischemic
      Syndrome Management in Patients Limited by Unstable Signs and Symptoms trial.
      Five independent predictors were identified: age >65 years, prior coronary artery
      bypass grafting, antecedent aspirin use, antecedent beta-blocker use, and ST
      depressions on the presenting electrocardiogram. A risk score system was created
      using these predictors in which patients were assigned 1 point for the presence
      of each risk factor. There was a progressive increase in the rate of the
      composite end point of death, myocardial infarction, or refractory ischemia at 7
      days with an increasing number of risk factors. For patients treated with heparin
      alone, the composite end point event rate was 6.5% in the group with 0 or 1
      predictor, 14.6% in the group with 2 predictors, 22.7% in the group with 3
      predictors, and 37.1% in the group with 4 or 5 predictors (p <0.00001). When
      dividing patients into low- (0 or 1 point), medium- (2 or 3 points), and high
      risk (4 or 5 points) groups, the addition of tirofiban to heparin therapy was
      associated with no significant benefit in the low-risk group, a 5.2% absolute
      reduction in the medium-risk group (p = 0.05), and a 16% absolute reduction in
      the high-risk group (p = 0.0055). Thus, we have developed a risk score system
      using 5 variables that can be used to identify patients at high risk for death
      and cardiac ischemic events and who experience the greatest benefit from the
      addition of a glycoprotein IIb/IIIa inhibitor to their treatment regimen.

PMID- 11524056
TI  - Vascular closure devices and the risk of vascular complications after
      percutaneous coronary intervention in patients receiving glycoprotein IIb-IIIa
      inhibitors.
AB  - Vascular closure devices offer advantages over traditional means of obtaining
      hemostasis after percutaneous coronary intervention (PCI) in terms of patient
      comfort and time to ambulation. We investigate whether such devices also reduce
      the risk of vascular complications in selected patient populations. We conducted
      a retrospective analysis of all patients who underwent PCI at our institution
      between January 1998 and December 1999. Of 3,151 consecutive patients, 3,027 were
      eligible to receive vascular closure devices. Of these, 1,485 received a closure
      device and 1,409 received glycoprotein IIb-IIIa antagonists. The overall vascular
      complication rate, as defined by the need for surgical repair or transfusion, or
      the development of arteriovenous fistula, pseudoaneurysm, or large hematoma, was
      4.20%. By univariate analysis, the use of closure devices was associated with a
      lower vascular complication rate (3.03% vs 5.52%; p = 0.002) and a shorter length
      of hospital stay (2.77 vs 3.97 days, p <0.001). Multivariate analysis showed a
      significant reduction in vascular complications with closure devices (odds ratio
      0.59, p = 0.007). For the subgroup of patients receiving glycoprotein IIb-IIIa
      antagonists, the use of closure devices was associated with an even more
      pronounced reduction in the risk of vascular complications (odds ratio 0.45, p
      <0.008). Thus, the use of closure devices in selected patients undergoing PCI is
      associated with a low rate of vascular complications and decreased length of
      stay. This benefit was most marked for patients receiving glycoprotein IIb-IIIa
      antagonists.

PMID- 11524057
TI  - Trends in outcome and costs of coronary intervention in the 1990s.
AB  - Our objective was to examine trends in outcome and cost of percutaneous coronary
      intervention (PCI) between 1990 and 1999. PCI has become the most common form of
      myocardial revascularization in recent years, rivaling the more established
      coronary artery bypass surgery. There has been increasing interest in improving
      outcome of PCI while also seeking to minimize cost. A total of 21,755 patients
      undergoing PCI were evaluated. Clinical data were gathered from the Emory
      Cardiovascular Database and financial data from the UB92 formulation of the
      hospital bill. Charges were reduced to cost using departmental cost-to-charge
      ratios. Costs were inflated to 1999 dollars using medical care inflation rates.
      Mortality varied without a significant trend from 0.63% to 0.44% (p = 0.64). The
      Q-wave myocardial infarction rate decreased from 0.68% to 0.40% (p = 0.0003).
      Emergent coronary surgery decreased from 3.50% to 1.25% (p <0.0001). Mean
      hospital inflation-adjusted cost decreased from $10,478 to $8,367 (p <0.0001).
      Length of stay after the procedure decreased from 2.8 to 1.8 days (p <0.0001).
      Outcome of PCI continues to improve, with a decrease in coronary surgery and Q
      wave myocardial infarction but with no significant change in mortality. This was
      accomplished while also decreasing costs and length of stay. Whether these
      favorable trends will continue remains to be seen.

PMID- 11524058
TI  - Effect of rosuvastatin on low-density lipoprotein cholesterol in patients with
      hypercholesterolemia.
AB  - Rosuvastatin is a new, synthetic, orally active statin, with marked low-density
      lipoprotein (LDL) cholesterol-lowering activity. We conducted 2 dose-ranging
      studies. In the first study, after a 6-week dietary run-in, 142 moderately
      hypercholesterolemic patients were randomized equally to receive double-blind
      placebo or rosuvastatin 1, 2.5, 5, 10, 20, or 40 mg or open-label atorvastatin 10
      or 80 mg once daily for 6 weeks; in the second study, conducted to extend the
      rosuvastatin dose range, 64 patients were randomized to double-blind, once-daily
      placebo or rosuvastatin 40 or 80 mg (1:1:2 ratio) for 6 weeks. Data from both
      studies were combined for analysis of lipid effects. No statistical comparison of
      atorvastatin arms with placebo or rosuvastatin was performed. Rosuvastatin was
      associated with highly significant dose-dependent reductions in LDL cholesterol
      compared with placebo (p <0.001); decreases ranged from 34% (1 mg) to 65% (80
      mg). Linear regression analysis indicated an additional 4.5% LDL cholesterol
      reduction for each doubling of the rosuvastatin dose. Across the dose range,
      approximately 90% of LDL cholesterol reduction occurred within the first 2 weeks
      of treatment. Significant, dose-dependent reductions in total cholesterol and
      apolipoprotein B with rosuvastatin were also observed (p <0.001). High-density
      lipoprotein cholesterol increases and triglyceride reductions were consistently
      observed and statistically significant at some dose levels. All lipid ratios were
      significantly reduced at all rosuvastatin dose levels (p <0.001). Adverse events
      were similar across placebo and active treatments. No significant increases in
      alanine aminotransferase or creatine kinase were seen in any patient. Over 6
      weeks, rosuvastatin produced large, rapid, dose-dependent LDL cholesterol
      reductions and was well tolerated in hypercholesterolemic patients.

PMID- 11524059
TI  - Usefulness of the Framingham risk score and body mass index to predict early
      coronary artery calcium in young adults (Muscatine Study).
AB  - The value of a coronary artery disease prediction algorithm, the Framingham risk
      score (score), for detecting coronary artery calcium (CAC) was examined in 385
      men and 472 women, aged 29 to 43 years. Scores were compared in subjects with and
      without CAC and were also used to predict presence of CAC. Receiver-operating
      characteristic curves were computed to compare different prediction models. The
      score model was compared with age only, natural logarithm of body mass index
      (lnBMI) only, and score plus lnBMI models. CAC was detected in 30% of men and 16%
      of women. The mean score was significantly higher in men and women with CAC. For
      every 2-point increase in the score, the odds of CAC increased by 30% in women
      and 20% in men. Significant associations between CAC status and risk factors were
      observed for age in women, and high- density lipoprotein cholesterol and blood
      pressure in men and women. The area under the receiver-operating characteristic
      curve for the score was 0.67 and 0.57 for women and men, respectively. When lnBMI
      was added to the score model, the area increased to 0.76 in women (lnBMI p
      <0.0001, score p <0.005). For men, the area increased from 0.57 to 0.67, and the
      score was no longer significant (p >0.60) in the model with lnBMI (p <0.0001).
      Score predicts CAC in asymptomatic young adults. Inclusion of lnBMI in the score
      model adds significantly to the prediction of CAC in women and men. The lnBMI
      model has a greater predictive value than the score in this young population.

PMID- 11524060
TI  - Survival benefit with an implanted defibrillator in relation to mortality risk in
      chronic coronary heart disease.
AB  - Although improved patient survival has been reported in several randomized trials
      with the implanted cardioverter-defibrillator, <15% of patients treated with
      defibrillators during trials receive life-saving benefit from this therapy. We
      evaluated the survival benefit from defibrillator therapy in relation to the
      severity of the mortality risk in patients with coronary heart disease. Using
      data from the Multicenter Automatic Defibrillator Implantation Trial, we
      partitioned the study population into high- and low-risk subsets for each of 3
      physiologically meaningful risk factors (ejection fraction, QRS duration, and
      history of heart failure requiring therapy). Risk of death was evaluated by Cox
      proportional-hazards regression analyses in patients with single and multiple
      risk factors. The defibrillator was associated with a significant (p = 0.002)
      reduction in mortality only in high-risk subsets with ejection fraction <0.26,
      QRS duration > or =0.12 second, and history of heart failure requiring treatment.
      The Cox hazard ratio for the risk of death progressively increased >1.0 as a
      function of the number of risk factors present. Defibrillator therapy was
      associated with a progressive reduction in the hazard ratio <1.0 (improved
      survival) at each increased level of mortality risk. Patients at the highest
      mortality risk (all 3 risk factors; hazard ratio 4.33) achieved the largest
      mortality reduction (hazard ratio 0.20) from defibrillator therapy. In patients
      with chronic coronary heart disease, the magnitude of the survival benefit from
      the implanted defibrillator is directly related to the severity of cardiac
      dysfunction and its associated mortality risk.

PMID- 11524061
TI  - Effect of regression of left ventricular hypertrophy from systemic hypertension
      on systolic function assessed by midwall shortening (HOT echocardiographic
      study).
AB  - Depressed midwall shortening has been shown to be an independent predictor of
      cardiovascular morbid events in hypertensive patients with left ventricular (LV)
      hypertrophy despite normal endocardial fractional shortening. The effects of LV
      mass changes in hypertensive patients on midwall shortening are unclear. To
      determine the impact of LV hypertrophy regression on LV systolic function
      assessed at the endocardium and the midwall level, 508 patients (58% men, 57%
      Caucasians, mean age 60 +/- 7 years) participating in the Hypertension Optimal
      Treatment study were prospectively studied by serial echocardiography at
      baseline, year 1, year 2, and at the end of the study. The Hypertension Optimal
      Treatment study was designed to challenge the existence of the J-curve phenomenon
      in hypertension. This study enrolled men and women between 50 and 80 years of age
      with mild to moderate hypertension. Patients were treated with a regimen based on
      felodipine with the addition of other antihypertensive drug classes as needed to
      reduce the diastolic blood pressure to a predefined target of < or =80, < or =85,
      or < or =90 mm Hg. From baseline to year 1, year 2, and end of the study, body
      mass index was unchanged (30.4, 30.1, 30.2, and 30.5 kg/m(2)); however, diastolic
      blood pressure was significantly reduced (99, 83, 80, and 80 mm Hg, p <0.0001),
      as was systolic blood pressure (161, 139, 137, and 134 mm Hg, p <0.0001) and LV
      mass index (117, 119, 107, and 106 g/m(2), p <0.0001). Over the same period of
      observation the endocardial fractional shortening did not change significantly
      (40%, 42%, 43%, and 44%); however, shortening at the midwall level showed
      improvement (20%, 21%, 22%, and 30%, p <0.001). In conclusion, midwall shortening
      is a more sensitive index of systolic function in subjects with pressure-overload
      hypertrophy, and it identifies high-risk patients who may benefit from a more
      aggressive antihypertensive program. The disparity between midwall and
      endocardial shortening suggests reduced myofibril function in patients with
      hypertension-induced hypertrophy.

PMID- 11524062
TI  - Prognostic importance of marital quality for survival of congestive heart
      failure.
AB  - Mounting evidence indicates that social support is associated with better
      outcomes of cardiovascular disease and reduced all-cause mortality. Much less is
      known about the specific contribution of marital functioning to these outcomes,
      and the potential prognostic significance of marital quality for congestive heart
      failure (CHF) has not been explored. Interview and observational measures of
      marital quality obtained from 189 patients with CHF (139 men and 50 women) and
      their spouses were examined as predictors of patient survival up to 48 months
      after assessment and compared with prediction based on illness severity (New York
      Heart Association [NYHA] class). Four-year survival rates were 52.5% and 68% for
      male patients and female patients, respectively. In Cox regression analyses, a
      composite measure of marital quality predicted 4-year survival as well as the
      patient's concurrent NYHA class did (both p <0.001). Adjusting for CHF severity
      did not diminish the prognostic significance of marital functioning, and
      prediction of survival from marital quality appeared stronger for female than for
      male patients. Thus, when marital quality and NYHA class are considered jointly,
      they both make independent, statistically significant contributions to the
      prediction of patient mortality.

PMID- 11524063
TI  - Mortality and readmission of hospitalized patients with congestive heart failure
      and preserved versus depressed systolic function.
AB  - Patients with congestive heart failure (CHF) and preserved systolic function are
      very common. Despite the high prevalence of this syndrome, very little
      information is known regarding its mortality and morbidity (e.g., readmission),
      or the efficacy of drugs. The purpose of this study was to compare the clinical
      characteristics and prognosis among consecutively hospitalized patients with CHF
      and preserved versus depressed left ventricular systolic function. Patients with
      severe aortic or mitral valve disease were excluded from the study. Patients were
      categorized based on the values of ejection fraction (EF) as having "preserved"
      (EF>50%), "intermediate" (EF 40% to 50%), or "depressed" (EF<40%) systolic
      function. Clinical characteristics as well as mortality and hospital readmission
      rates during 2.4 years of follow-up were recorded for each patient. Sixty-one
      patients (35%) had preserved systolic function, 73 (43%) had depressed function,
      and 38 (22%) had intermediate function. Patients with preserved systolic function
      were more often women and had a higher prevalence of left ventricular hypertrophy
      (all p <0.05). At follow-up, cumulative survival probabilities were similar
      between patients with preserved systolic function and those with systolic
      dysfunction (p = 0.84). Readmission rates were also comparable between preserved
      and depressed systolic function (36% vs 48%; p = NS). The prognosis of CHF
      patients with preserved systolic function was similar to those with systolic
      dysfunction. In light of these findings, effective therapeutic strategy for this
      subset of patients is needed.

PMID- 11524064
TI  - Value of quantitative analysis of mitral regurgitation jet eccentricity by color
      flow Doppler for identification of flail leaflet.
AB  - Early surgical intervention improves the outcome of patients with mitral
      regurgitation (MR) secondary to flail leaflet. Current criteria for the diagnosis
      of flail leaflet require a detailed definition of mitral valve anatomy, which is
      often challenging by transthoracic echocardiography (TTE) and, occasionally, even
      by transesophageal echocardiography (TEE). We studied 57 patients (mean age 63 +/
      15 years) with anatomically confirmed flail mitral leaflet and a control group
      of 57 patients (mean age 68 +/-14 years) with at least moderate MR but no flail
      leaflet. In patients with flail mitral leaflet, the mean angle formed by the axis
      of the MR jet and the plane of the mitral annulus was 33 +/- 11 degrees and 29 +/
      16 degrees when measured with TTE and TEE, respectively. In controls the mean
      angle was 66 +/- 16 degrees and 66 +/- 17 degrees by TTE and TEE, respectively (p
      <0.0001). Based on receiver- operating characteristic analysis, the optimal
      cutoff jet angle value for diagnosing flail mitral leaflet was 45 degrees with
      TTE (sensitivity 88%, specificity 88%), and 47 degrees by TEE (sensitivity 88%,
      specificity 88%). MR jet angles < or =45 degrees were also correctly identified
      by visual assessment of TTE images in >90% of cases, with good interobserver
      agreement (k = 0.76). Thus, quantitative analysis of MR jet eccentricity by color
      flow Doppler is highly sensitive and specific for diagnosing flail mitral
      leaflet.

PMID- 11524065
TI  - Comparison of two aspirin doses on ischemic stroke in post-myocardial infarction
      patients in the warfarin (Coumadin) Aspirin Reinfarction Study (CARS).
AB  - The Coumadin Aspirin Reinfarction Study demonstrated that combination treatment
      with fixed dose warfarin (1 or 3 mg) + aspirin 80 mg was not superior to aspirin
      160 mg alone after myocardial infarction for reducing nonfatal reinfarction,
      nonfatal stroke, and cardiovascular death. In this analysis, we examined the
      importance of aspirin dose in the protection against the secondary end point of
      ischemic stroke. The comparison arms for this analysis were warfarin 1 mg +
      aspirin 80 mg versus aspirin 160 mg. In the Coumadin Aspirin Reinfarction Study,
      2,028 patients were randomized to aspirin 80 mg plus warfarin 1 mg, and 3,393
      were randomized to aspirin 160 mg alone. A predictive model for ischemic stroke
      was developed using the Cox proportional-hazards model. A reduced Cox
      proportional-hazards model was developed to test for the effect of aspirin dose
      on ischemic stroke in predefined subgroups. The incidence of ischemic stroke was
      lower in patients treated with aspirin 160 mg than in patients treated with
      aspirin 80 mg + warfarin 1 mg (0.6% vs 1.1%; p = 0.0534). Age, previous stroke or
      transient ischemic attack, and aspirin dose were independent predictors of
      ischemic stroke. In addition, the highest risk patients, those with Q-wave
      myocardial infarction and male patients, appeared to receive greater benefit from
      aspirin 160 mg than from aspirin 80 mg + warfarin 1 mg. The results of this
      secondary analysis suggest that aspirin 160 mg is more effective than aspirin 80
      mg + warfarin 1 mg in preventing ischemic stroke in post-myocardial infarction
      patients.

PMID- 11524066
TI  - Alfred Lewis Galabin and the first human documentation of atrioventricular block.
AB  - Using an apexcardiogram, Galabin was the first person to document
      atrioventricular (AV) block in humans. He performed his studies while working as
      a house officer at Guy's Hospital, London, United Kingdom. His patient was 34
      years old, experienced attacks of near syncope, and had a pulse rate that varied
      between 25 and 30 beats/min. A laddergram of the patient's apexcardiogram
      suggests advanced AV block with 3 to 1 and 2 to 1 AV conduction with Wenckebach
      periodicity. We review the history of AV block beginning with the introduction of
      graphic recordings in 1847 by Ludwig, and include the contributions of Stannius,
      Luciani, Gaskell, Wenckebach, Hay, and Mobitz. Although he is little known today
      among cardiovascular physicians, we recognize Galabin as the first person to
      demonstrate AV block in humans.

PMID- 11524067
TI  - West meets East: breaking barriers to prevention in Asia and America.

PMID- 11524068
TI  - Effect of ingestion of purple grape juice on endothelial function in patients
      with coronary heart disease.

PMID- 11524069
TI  - Incidence of new coronary events in older persons with diabetes mellitus and
      prior myocardial infarction treated with sulfonylureas, insulin, metformin, and
      diet alone.

PMID- 11524070
TI  - Relation of pathologic Q waves at presentation and time to streptokinase therapy
      with early changes in infarct-related artery flow and ventricular wall motion.

PMID- 11524071
TI  - How many patients with ischemic cardiomyopathy exhibit viable myocardium?

PMID- 11524072
TI  - Incidence, management, and outcome of stent loss during intracoronary stenting.

PMID- 11524074
TI  - Clinical characteristics and possible mechanism of paroxysmal atrial fibrillation
      induced by intracoronary injection of acetylcholine.

PMID- 11524073
TI  - Effect of diltiazem on the recurrence rate of paroxysmal atrial fibrillation.

PMID- 11524075
TI  - Mapping and ablation of atrial arrhythmias after surgical correction of
      congenital heart disease guided by a 64-electrode basket catheter.

PMID- 11524076
TI  - Evidence for increased peripheral production of tumor necrosis factor-alpha in
      advanced congestive heart failure.

PMID- 11524077
TI  - Association between mitral annular calcium and carotid artery stenosis and role
      of age and gender.

PMID- 11524078
TI  - Efficacy of nonsurgical septal reduction therapy in symptomatic patients with
      obstructive hypertrophic cardiomyopathy and provocable gradients.

PMID- 11524079
TI  - Late follow-up of occlusion of the patent ductus arteriosus with the Rashkind
      device with emphasis on long-term efficacy and risk for infections.

PMID- 11524080
TI  - Comparison of results of closure of secundum atrial septal defect by surgery
      versus Amplatzer septal occluder.

PMID- 11524081
TI  - Usefulness of corticosteroid therapy in decreasing epinephrine requirements in
      critically ill infants with congenital heart disease.

PMID- 11524082
TI  - Intensive isotonic training modifies basal and exercise Doppler indexes of
      systolic function: a comparative study of athletes and sedentary men.

PMID- 11524083
TI  - Growth factor expression during the development of atrophic non-union.
AB  - The aim of the study was to determine, for the first time, the distribution of
      expression of several important growth factors during the development of atrophic
      non-unions using an animal model. The sites of expression of TGFbeta, PDGF, FGFb,
      and BMP 2/4 were determined at the osteotomy sites of both normally healing bones
      and within atrophic non-unions at 1 and 8 weeks after operation using
      immunolocalization techniques. At 1 week after operation, the osteotomy gaps of
      the control group contained fracture haematoma and surrounding granulation
      tissue, whereas the osteotomy gaps of the non-union group contained only
      haematoma. The tissues of both the non-union and control groups demonstrated the
      same presence and distribution of growth factors. By 8 weeks after the operation,
      the control group osteotomy gaps were filled with bone within which the active
      osteoblasts stained positively for each of the growth factors. At 8 weeks, the
      osteotomy gaps of the non-union group contained only fibrous tissue, which failed
      to stain positively for any of the factors. These findings suggest that the
      development of atrophic non-union is not directly due to a lack of these four
      growth factors.

PMID- 11524084
TI  - Clinical pathways--can they be used in trauma care. An analysis of their ability
      to fit the patient.
AB  - This study prospectively evaluated the appropriateness and ability of clinical
      pathways to fit trauma patients in five key conditions, severe head injury,
      fractured ribs, fractured pelvis, fractured femur and blunt abdominal trauma, who
      were admitted to a single Level 1 Trauma Centre, between February and July 1999.
      Each pathway consisted of 14 elements of care divided into observable outcomes.
      Failure to achieve an outcome resulted in a variance or deviation from the
      pathway, which was assessed by the number of non-applicable variances.
      Appropriateness of clinical pathways was assessed by the applicability index (the
      number of non-applicable variances divided by the potential variances). Critical
      mismatches occurred when non-applicable variances exceeded 50% of potential
      variances. 146 patients, with the mean age 41.9 years (S.D. 20.7), mean ISS 11.1
      (S.D. 10.7) were enrolled; 18 with severe head injury, 59 with fractured ribs, 13
      with fractured pelvis, 20 with fractured femur and 36 with blunt abdominal
      trauma. Critical mismatch occurred in seven patients. Applicability indexes were
      87 for head, 93 for ribs, 92 for blunt abdominal trauma, 91 for femur and 92 for
      the pelvic pathway. Patient assessment, pain management, skin integrity and
      patient education were the most appropriate key elements of care, discharge
      planning, patient satisfaction, treatment and activity were least applicable.
      This study identified, for the first time, that clinical pathways are clinically
      appropriate for major trauma conditions.

PMID- 11524085
TI  - Penetrating cardiac injuries: a complex challenge.

PMID- 11524087
TI  - Penetrating trauma in patients older than 55 years: a case-control study.
AB  - BACKGROUND: Multiple studies have compared young and elderly blunt trauma
      patients, and concluded that, because elderly patients have outcomes similar to
      young patients, aggressive resuscitation should be offered regardless of age.
      Similar data on penetrating trauma patients are limited. STUDY DESIGN: In a
      retrospective review, 79 patients with penetrating injuries and age > or =55 were
      blindly matched for Injury Severity Score (ISS) and Abbreviated Injury Scores
      (AIS) with 79 penetrating trauma patients aged 15-35 years, who were admitted to
      the hospital over the same 4 year period (June 1994-June 1998). Mortality rates
      and length of stay in the intensive care unit (ICU) and the hospital were
      compared between the two groups. RESULTS: The average ISS for all patients was 12
      (range 1-75) and identical for both groups. Both groups had similar injuries and
      were evaluated by an equal number and type of diagnostic studies. The mean ISS
      was not different between severely injured older and younger patients who
      required ICU admission or died. Among 32 nonsurvivors (18 older and 14 younger),
      older patients were more likely than younger patients to present with normal
      vital signs, although the comparison did not reach statistical significance (50%
      vs. 13%, P=0.25). There was a clinically significant trend for longer ICU (15+/
      30 vs. 3+/-2 days, P=0.096) and hospital stay (10+/-18 vs. 6+/-8 days, P=0.08)
      among older patients, but mortality rates were similar (23% in older vs. 18% in
      younger, P=NS). Furthermore, these outcome parameters showed no difference when
      both groups were classified according to severity of injury or physiologic
      response. CONCLUSIONS: Following penetrating trauma, older patients arriving
      alive and admitted to the hospital are as likely to survive as younger patients
      who have injuries of similar severity, but at the expense of longer ICU and
      hospital stays.

PMID- 11524086
TI  - The role of oral contrast administration immediately prior to the computed
      tomographic evaluation of the blunt trauma victim.
AB  - BACKGROUND: It is unclear whether the administration of oral contrast followed by
      immediate computerised tomographic (CT) scanning presents a significant risk of
      aspiration and whether it is useful in the diagnosis of hollow viscus injury.
      OBJECTIVE: Determine the number of intestinal perforations diagnosed by oral
      contrast enhanced CT scans for blunt trauma and identify those who developed
      aspiration pneumonitis causally related to oral contrast administration. METHODS:
      We analysed a database of consecutive blunt trauma admissions over a 2-year
      period. The majority received oral contrast immediately prior to CT scanning. We
      determined the number of intestinal perforations identified by abdominal CT
      confirmed at laparatomy and the number of cases of aspiration pneumonia. RESULTS:
      Nine (1%) of the 1173 CT scans identified enteric perforations. Oral contrast
      enhanced CT scans demonstrated pneumoperitoneum (3), extraluminal contrast
      extravasation (2), and the presence of free fluid with small bowel wall
      thickening (8). In this same cohort, eight (0.7%) cases of aspiration pneumonia
      were diagnosed within 48 h of admission in patients with a mean GCS of 4.25; only
      one (0.1%) was temporally related to oral contrast administration. In a
      prospective study, none of the 65 consecutive patients who received oral contrast
      had witnessed aspiration. CONCLUSIONS: Oral contrast administration given
      immediately prior to CT scanning does not increase the risk of clinically
      significant aspiration and assists in the detection of enteric perforation.

PMID- 11524088
TI  - Further experience of nonagenarians with hip fractures.
AB  - Our purpose was to investigate the factors after predictive outcome 3 months
      after the injury in terms of mortality and effective independent walking of
      nonagenarians with hip fracture. A prospective study was carried out for 2 yr in
      the orthopaedic wards on patients referred to geriatricians. The data were
      subjected to logistic regression forward stepwise analysis. Eighty-nine patients
      were included in the study; 55 (61.8%) had a trochanteric fracture and 86
      required a surgical procedure. Before the fracture, 83 patients (93.3%) were able
      to walk by themselves or with minimal supervision. Forty-three patients (48.3%)
      had an American Society of Anaesthesiologists' of III-IV score. The mean number
      of postoperative complications was four. Mean hospital stay was 18.2 days. Within
      3 months, 19 patients (21.3%) had died and 58 (69%) were living in their previous
      residence. Thirty-three (50% of living patients) were able to walk by themselves
      or with minimal help within 3 months of the fracture. Predictive variables for 3
      month mortality were pre-fracture dependence on others for personal toilet and
      the presence of cognitive impairment. Predictive variables for independent
      efficient walking were bowel control and absence of cognitive impairment before
      the fracture, as well as no development of bed sores during hospitalization.These
      nonagenarian patients with hip fractures show low perioperative mortality,
      frequently return to their previous accommodation and present a limited recovery
      of walking ability.

PMID- 11524089
TI  - Internal fixation of ankle fractures in the very elderly.
AB  - The management of ankle fracture in the elderly remains controversial. A review
      of the early results of open reduction and internal fixation (ORIF) in 74
      patients over the age of 70 years (average 76 years) was undertaken to identify
      the early complications, length of stay, return to pre-injury mobility and
      residential status. This revealed 1% deep infection, 9% delayed wound healing, 5%
      malunion, and 3% mortality. In 12% of patients, soft bone and comminution
      precluded fixation of one malleolus. The average length of stay for patients who
      walked with Zimmer frame (116+/-65 days) before injury was significantly longer
      than those who walked independently or with sticks (19+/-15 days; P<0.01). The
      inability of the patients to weight-bear early led to lengthy hospital stays and
      difficult socio-economic problems. However, the majority (85%) of patients
      regained their pre-injury mobility and residential status. We conclude that ORIF
      of ankle fractures in the elderly carries a significant risk of wound edge
      necrosis with delayed wound healing but the incidence of deep infection is
      relatively low. Poor bone quality presents technical difficulties but the
      majority of patients can expect good outcome.

PMID- 11524090
TI  - Vertebral artery injury in cervical spine trauma.
AB  - Forty-seven patients with cervical spine trauma were evaluated prospectively with
      magnetic resonance imaging (MRI) and angiography (MRA) to determine the incidence
      of vertebral artery injury. Twelve patients (25%) had vertebral artery injuries
      (one bilateral), and occlusion was identified in nine patients and dissection in
      four. The vertebral artery injury did not result in neurological dysfunction. No
      specific treatment was instituted for the vascular injury, and in four patients,
      MRA showed no evidence of recanalization at follow-up.

PMID- 11524091
TI  - Clinical features, patterns of referral and out of hospital transport events for
      patients with suspected isolated spinal injury.
AB  - BACKGROUND: Prehospital diagnostic accuracy and risks of transportation
      associated neurological deterioration for patients with spinal injury remain
      imprecise. METHODS: Retrospective review of medical records for patients with
      suspected spinal injury assessed and escorted by medically staffed team. RESULTS:
      One hundred and ninety six patients had follow up for spinal injury, 61% with
      actual injury. Of the 196 patients, 93% involved helicopter transport, 3.5% road
      vehicle and 3.5% fixed wing transports. Fifty one percent were interhospital
      transfers. Medical team's scene diagnostic accuracy of spinal injury was 31%.
      Scene medical interventions were those consistent with current paramedical
      skills. Of interhospital transferred patients, 19% had no injury. Cervical
      injuries as part of mixed injuries were the most often missed injuries. Abnormal
      neurological findings occurred equally amongst patients with and without spinal
      injury. Transport related incidents were documented for 15%. Interhospital
      transport patient related incidents occurred for 12% helicopter and 36% road
      vehicle transports (P=0.094). No transport related neurological injury or other
      morbidity was documented. CONCLUSION: Prehospital diagnosis of spinal injury,
      even by medical teams remains imprecise. Choice of helicopter transport, based
      purely upon the suspected presence of spinal injury could not be supported.

PMID- 11524092
TI  - Prophylactic carpal tunnel decompression during buttress plating of the distal
      radius--is it justified?
AB  - Our objective was to evaluate the role of carpal tunnel decompression in
      preventing median nerve dysfunction after buttress plating of the distal radius.
      We studied 69 consecutive patients with distal radial fractures managed by volar
      plating over a 4-year period. (1995-1998). Patients' clinical notes were assessed
      for symptoms of median nerve dysfunction and all the patients were followed up
      for a minimum period of 6 months. Twenty-four patients had prophylactic carpal
      tunnel decompression and 45 patients did not. Forty-two patients (61%) were women
      and 27 patients (39%) men. The average age of the patients was 56 years, (range
      24-81 years). Overall 17 patients (25%) developed median nerve dysfunction post
      operatively of which nine patients had and eight patients did not have formal
      prophylactic tunnel decompression, respectively; this was not statistically
      significant (P=0.08). In addition prophylactic decompressed patients had more
      than twice the relative odds=2.7 (confidence interval: CI=0.94-4.76) of
      developing median nerve dysfunction. All cases resolved spontaneously except for
      three cases that required carpal tunnel decompression. We conclude that
      prophylactic median nerve decompression does not alter the course of median nerve
      dysfunction and may increase post-operative morbidity.

PMID- 11524094
TI  - Trans iliac-sacral-iliac bar stabilisation to treat bilateral lesions of the
      sacro-iliac joint or sacrum: anatomical considerations and clinical experience.
AB  - The use of trans iliac-sacral-iliac bars is an alternative to sacro-iliac screws
      in the treatment of bilateral lesions of the posterior pelvic ring, and the same
      biomechanical principles can be applied. Of 20 patients, ten men and ten women, a
      CT-scan of the pelvis was performed to study the individual and common safe area
      at the level of S1 and S2. The location and maximal diameter of the individual
      safe area were studied using a computer-navigation system, displaying images in
      sagittal, coronal and axial anatomic planes together with a 3-D reconstruction.
      The common safe area was studied using three points: upper- (UA) and lower
      anterior corner (DA) of S1 and S2, and the centre of the safe area. It would have
      been possible to place an iliac-sacral-iliac bar (5 mm or more) in S1 and S2 in
      all the men, but in the women a bar could only have been inserted in only five in
      S1 and eight in S2. A statistically significant difference between men and women
      was found at S1 (P=0.033) but not at S2 (P=0.211). No significant correlation was
      found between the diameter of the safe area at both levels in men and women and
      age, height, and weight. Furthermore, no common safe area of 5 mm or more was
      measured at the same levels.Four patients were treated using trans iliac-sacral
      iliac bars. Three were placed under fluoroscopic control in combination with a
      frame, and in one patient an image-guided system was used. A postoperative CT
      confirmed the correct position of the bars in each patient. The complexity and
      individual variability of the sacrum makes complex preoperative planning of the
      iliac-sacral-iliac path mandatory.

PMID- 11524093
TI  - Operative management of acetabular fractures in Oxford.
AB  - We reviewed the epidemiology and complications of 79 patients who had operative
      treatment for an acetabular fracture undertaken at this hospital, in the first 5
      years of a pelvic and acetabular fracture service. The median Injury Severity
      Score was 18 (range, 9-41). Sixty-five patients (82%) had an important injury of
      at least one other system. Eighteen patients (23%) had a sciatic nerve injury on
      presentation. Thirty-seven patients (47%) had a post-operative complication, but
      this did not affect the outcome in the majority. The re-operation rate was
      5%.Seventy-four patients (94%) had clinical and radiological follow-up for a mean
      of 2.6 years. Fifty-five patients (74%) had a good or excellent result, which was
      associated with early operation and an anatomical reduction. Poor outcome was
      associated with delay to surgery, failure to achieve or maintain reduction, and
      femoral head damage at the time of injury.

PMID- 11524096
TI  - How much do we know about the giving and receiving of information?

PMID- 11524097
TI  - The development of the Chemotherapy Symptom Assessment Scale (C-SAS): a scale for
      the routine clinical assessment of the symptom experiences of patients receiving
      cytotoxic chemotherapy.
AB  - The management of symptoms experienced by patients receiving cytotoxic
      chemotherapy influences quality of life during treatment. Symptom management may
      be improved through a structured approach to symptom assessment. This paper
      describes the development of the Chemotherapy Symptom Assessment Scale (C-SAS), a
      24-item scale designed for the routine assessment of symptoms experienced by
      patients receiving cytotoxic chemotherapy. The scale development process focused
      both upon the psychometric properties and the clinical usefulness of the scale.
      Patients and health professionals played a significant role in item selection and
      scale design in order to maximise the clinical utility of the C-SAS.

PMID- 11524098
TI  - A 35-item version of the Caring Dimensions Inventory (CDI-35): multivariate
      analysis and application to a longitudinal study involving student nurses.
AB  - The present study was designed to investigate the perceptions of caring among
      student nurses and how these develop throughout the course of a programme of pre
      registration nurse education. A 35-item version of the caring dimensions
      inventory was administered to a cohort of nursing students in a department of
      nursing in Scotland at entry to the programme, after 12 months and after 24
      months on the programme. Caring was largely perceived through a technical
      dimension, demonstrated by factor analysis, but other dimensions such as
      intimacy, support and unnecessary and inappropriate aspects of nursing also
      became apparent as students progressed through the programme.

PMID- 11524099
TI  - Making sense of the voices.
AB  - Hearing voices is a common occurrence, and an experience of many people in
      psychiatric/mental health care. Nurses are challenged to provide care, which is
      empowering and helps people who hear voices. Nursing practice undertaken in
      partnership with the voice hearer and informed by a working explanatory model of
      hallucinations offers greater helping potential. This paper uses Slade's (1976.
      The British Journal of Social and Clinical Psychology 15, 415-423.) explanatory
      model as a framework for exploring interventions which may assist people in
      exerting some control over the experience and which might be used alongside
      pharmacological interventions. Principles and practical ideas for how nurses
      might assist people to cope with and make sense of the experience are explored.

PMID- 11524100
TI  - The palliative management of fungating malignant wounds--generalising from
      multiple-case study data using a system of reasoning.
AB  - The project focused on individual experiences, from 45 participants, of living
      with a fungating wound and the performance of wound dressings in reducing the
      impact of the wounds on daily living. A case study design was adopted. This posed
      a key methodological challenge in the form of the contentious epistemological
      issue, characterised in the literature as the "nomothetic-idiographic dilemma".
      This issue concerns the nature of knowledge generated from an individual case and
      its generalisability. A system of reasoning was adopted as the analytic strategy,
      within a theory-driven evaluation, to abstract general issues from the case study
      data to construct explanations of symptom control and dressing performance. The
      latter were generalised beyond the individual cases with the use of theory. This
      paper focuses on the methodological issues that are inherent in the use of a case
      study design and the nature of the evidence generated. The system of reasoning is
      described and illustrated using data from a single participant with advanced
      uterine cancer and a fungating nodule in the groin.

PMID- 11524101
TI  - Partnerships identified within primary health care literature.
AB  - Primary health care promotes partnership in nursing. The purpose of this study
      was to delineate defining characteristics of partnerships within primary health
      care and to identify strategies to facilitate the development of these
      partnerships. Findings from this integrative review of the literature include the
      development of a partnership framework that emerged from the meanings inherent in
      the prefixes of words used to describe "multi", "inter", and "intra"
      partnerships. Also, the findings revealed characteristics of partner
      expectations, attributes of active and passive participation, and strategies to
      foster, and barriers to hinder, active participation. Using the developed
      partnership framework, implications for practice, education, and research have
      been discerned.

PMID- 11524102
TI  - The meaning of health-related quality of life in a Korean sample.
AB  - This study describes the impact of diabetes and the meaning of health-related
      quality of life (HRQOL) for 22 male and female patients in Korea. Open-ended
      interviews yielded six HRQOL themes: health, overall well-being, harmonious
      relationships and family responsibilities, a rewarding life, spiritual life, and
      material support. The physical impact of diabetes included decreased energy,
      limitations, and physical suffering; while its psychological/spiritual impact
      extended to general stress, helplessness, fear, depression, anger, and
      relationship with God. Like Americans, Koreans valued health, psychological well
      being and interpersonal support. In addition, the Koreans valued smooth,
      harmonious interpersonal relationships, overall well-being pertaining to living a
      comfortable and honorable life.

PMID- 11524103
TI  - Physical activity of Korean immigrant women in the U.S.: needs and attitudes.
AB  - The purpose of the study was to explore women's own needs for and attitudes
      toward physical activity among Korean immigrant women in the US using feminist
      approach and transition theory. This was a cross-sectional study consisting of
      quantitative and qualitative phases. Using convenience sampling methods, 54
      Korean immigrant women were recruited for the quantitative phase, and 15 women
      among them were recruited for the qualitative phase. Questionnaires and semi
      structured interviews were used to collect data. The data were analyzed using
      descriptive and inferential statistics and thematic analysis. The findings
      indicated that the women's needs for and attitudes toward physical activity were
      influenced by the contexts of their culture and immigration, and deeply
      associated with the women's daily experiences. Some implications for future
      research and nursing practice are proposed based on the findings.

PMID- 11524104
TI  - Balancing and compromising: nurses and patients preserving integrity of self and
      each other.
AB  - This paper brings together the perspective of both nurses and patients of the
      experience of nursing care delivery in acute care hospital settings. Initially,
      two grounded theory studies of the phenomenon of high-quality nursing care were
      conducted concurrently and in the same settings; one focussed on patients'
      experiences (Irurita, 1993. From person to patient: nursing care from the
      patient's perspective. Department of Nursing Research, Sir Charles Gairdner
      Hospital), the other on those of nurses (Williams, 1994. Unpublished report,
      Department of Nursing Research Sir Charles Gairdner Hospital, Perth, Western
      Australia). Similarities between the findings of both studies led the authors,
      using grounded theory methods, to re-examine and compare the findings and raw
      data, with additional data collected by theoretical sampling. The previous
      findings were integrated and extended, resulting in the development of a theory
      of Balancing and Compromising in response to the shared problem of threats to
      integrity, especially encountered when broader environmental and contextual
      conditions were unfavourable. This reciprocal process used by nurses and patients
      to preserve their own and each other's integrity involved: contributing to care-
      cooperating; prioritising and rational sacrificing; justifying compromised care
      and lowering expectations; and protecting self by attracting or repelling. Both
      positive and negative outcomes resulted.

PMID- 11524105
TI  - A study of the use of past experiences in clinical decision making in emergency
      situations.
AB  - Making decisions to call emergency assistance to patients is an important
      dimension of nursing practice. Most usually these decision making situations are
      uncertain and it is expected nurses rely on past clinical experiences. This
      study, approved by the ethics committees of both a university and an area health
      service, aimed to describe nurses' reliance on past experiences and identify
      associated judgement strategies (heuristics). Thirty-two registered nurses with
      five or more years experience were interviewed. Main findings were: nurses did
      use their past experiences and these experiences were used in the form of the
      three "classic" heuristics, representativeness, availability and anchoring and
      adjustment. It can be concluded past experiences are intrinsic to decision making
      and this has implications for both the clinical components of nursing educational
      programs and staffing allocations made by administrators. Some nurses, however,
      did not include referral to past experiences in their decision-making accounts
      which may be a limitation of the study design.

PMID- 11524106
TI  - Nurses' judgements of self-neglect: a factorial survey.
AB  - Self-neglect can be understood as the failure to engage in those activities which
      a given culture deems necessary to maintain a socially accepted standard of
      personal and household hygiene and carry out activities needed to maintain health
      status. Self-neglect is bound up in a discourse which equates dirt with disease
      and in which transgressions of self-care norms can be labelled as a medical
      syndrome. The notion of self-neglect as a social construction is the theoretical
      perspective which provides the framework for the study reported here. Judgements
      regarding self-neglect may be social judgements influenced by professional
      socialisation and cultural values. The belief that different groups of nurses may
      have different constructions of self-neglect will be investigated and the factors
      which influence these judgements will be explored in three groups of nurses. The
      inclusion of nursing students will allow some picture to emerge as to whether
      judgements develop over time or are relatively constant across the career path,
      albeit within the limitations of a non-longitudinal design.

PMID- 11524107
TI  - Responding to uncertainty in nursing practice.
AB  - Uncertainty is a fact of life for practising clinicians and cannot be avoided.
      This paper outlines the model of uncertainty presented by Katz (1988, Cambridge
      University Press, Cambridge, UK. pp. 544-565) and examines the descriptive and
      normative power of three broad theoretical and strategic approaches to dealing
      with uncertainty: rationality, bounded rationality and intuition. It concludes
      that nursing research and development (R&D) must acknowledge uncertainty more
      fully in its R&D agenda and that good-quality evaluation studies which directly
      compare intuitive with rational-analytical approaches for given clinical problems
      should be a dominant feature of future R&D.

PMID- 11524108
TI  - Taxol biosynthetic genes.
AB  - The function and properties of heterologously expressed full-length cDNA clones,
      isolated from a Taxus cDNA library and specific to Taxol biosynthesis, are
      summarized. Recombinant enzymes are described that catalyze early steps of the
      pathway, including taxadiene synthase, taxadien-5alpha-ol-O-acetyltransferase and
      taxadien-5alpha-yl acetate 10beta-hydroxylase, and that catalyze late steps,
      including 10-deacetylbaccatin III-10beta-O-acetyltransferase and taxane 2alpha-O
      benzoyltransferase. The properties of Taxus geranylgeranyl diphosphate synthase
      are also described; although this synthase does not mediate a committed step of
      Taxol biosynthesis, it does provide the universal plastidial diterpenoid
      precursor, geranylgeranyl diphosphate, for initiating Taxol biosynthesis.

PMID- 11524109
TI  - 18O pattern and biosynthesis of natural plant products.
AB  - Oxygen atoms in plant products originate from CO(2), H(2)O and O(2), precursors
      with quite different delta18O values. Furthermore their incorporation by
      different reactions implies isotope effects. On this base the resulting non
      statistical 18O distributions in natural compounds are discussed. The delta18O
      value of cellulose is correlated to that of the leaf water, and the observed 18O
      enrichment (approximately +27 per thousand) is generally attributed to an
      equilibrium isotope effect between carbonyl groups and water. However, as soluble
      and heterotrophically synthesised carbohydrates show other correlations, a non
      statistical 18O distribution - originating from individual biosynthetic reactions
      - is postulated for carbohydrates. Similarly, the delta18O values of organic
      acids, carbonyl compounds, alcohols and esters indicate water-correlated, but
      individual 18O abundances (e.g. O from acyl groups approximately +19% above
      water), depending upon origin and biosyntheses. Alcoholic groups introduced by
      monooxygenase reactions, e.g. in sterols and phenols, show delta18O values near
      +5 per thousand, in agreement with an assumed isotope fractionation factor of
      approximately 1.02 on the reaction with atmospheric oxygen (delta18O=+23.5 per
      thousand). Correspondingly, a "thermodynamically ordered isotope distribution" is
      only observed for oxygen in some functional groups correlated to an origin from
      CO(2) and H(2)O, not from O(2). The individual isotopic increments of functional
      groups permit the prediction of global delta18O values of natural compounds on
      the basis of their biosynthesis.

PMID- 11524110
TI  - Mechanisms of survival of necrotrophic fungal plant pathogens in hosts expressing
      the hypersensitive response.
AB  - The hypersensitive response (HR), elicited when resistant hosts are infected by
      incompatible races of biotrophic fungi, has been researched extensively. New
      studies on host responses to necrotrophic fungi are beginning to show that when
      the HR occurs in hosts colonized by necrotrophs, fungal growth is accelerated
      rather than retarded. We review current knowledge about how necrotrophs survive
      in host plants in which the HR is expressed. We discuss how necrotrophs cope with
      the environmental factors formed as a result of the HR. Necrotrophs contain an
      array of enzymes, which can help in exploiting the hostile environment in order
      to colonize the host and to remove or inactivate active oxygen species (AOS).
      Among this array of enzymes are superoxide dismutase (SOD), peroxidases,
      catalase, and perhaps laccases and polyphenol oxidases. Of these, only SOD and
      catalase have been studied in any detail. The precise significance of SOD and
      catalase in host invasion and fungal resistance is still not adequately known.
      The importance of different peroxidases is also still far from clear. We
      speculate that AOS species may trigger the response of necrotrophs to the host
      environment.

PMID- 11524111
TI  - Cloning of parsley flavone synthase I.
AB  - A cDNA encoding flavone synthase I was amplified by RT-PCR from leaflets of
      Petroselinum crispum cv. Italian Giant seedlings and functionally expressed in
      yeast cells. The identity of the recombinant, 2-oxoglutarate-dependent enzyme was
      verified in assays converting (2S)-naringenin to apigenin.

PMID- 11524112
TI  - First cyclotide from Hybanthus (Violaceae).
AB  - Hypa A, a novel macrocyclic polypeptide containing 30 amino acid residues, has
      been isolated from the n-butanol extract of the Argentine plant Hybanthus
      parviflorus. The sequence, cyclo-(SCVYIPCTITALLGCSCKNKVCYNGIPCAE), was determined
      by automated Edman degradation, quantitative amino acid analysis and nanospray
      MS/MS(2). Three intramolecular disulfide bridges stabilize the cyclic peptide
      backbone of hypa A. Using these structural features to classify the peptide as a
      cyclotide, we extended the distribution of that substance class to a new genus,
      and now propose a uniform nomenclature for cyclotides.

PMID- 11524113
TI  - 7-Deoxyloganin 7-hydroxylase in Lonicera japonica cell cultures.
AB  - The activity of 7-deoxyloganin 7-hydroxylase, an enzyme catalyzing the conversion
      of 7-deoxyloganin into loganin, was detected in a microsomal preparation from the
      cell suspension cultures of Lonicera japonica. It was dependent on NADPH and
      molecular oxygen. The enzymatic reaction was inhibited by carbon monoxide as well
      as by several cytochrome P450 inhibitors, especially ketoconazole, indicating
      that the reaction was mediated by cytochrome P450. The enzyme showed substrate
      specificity for 7-deoxyloganin. The K(m) values for 7-deoxyloganin and NADPH were
      estimated as 170 and 18 microM, respectively, from Lineweaver-Burk plots.

PMID- 11524114
TI  - Purification and characterization of two alpha-amylase inhibitors from seeds of
      tepary bean (Phaseolus acutifolius A. Gray).
AB  - Two proteinaceous alpha-amylase inhibitors termed alphaAI-Pa1 and alphaAI-Pa2
      were purified from seeds of a cultivated tepary bean (Phaseolus acutifolius A.
      Gray, cv. PI311897). The two inhibitors differed in their specificity towards
      alpha-amylases of insect pests such as bruchids, although neither showed any
      inhibitory activity against alpha-amylases of mammalian, bacterial or fungal
      origin. AlphaAI-Pa2 resembles two common bean inhibitors, alphaAI-1 and alphaAI
      2, in several characteristics such as N-terminal amino acid sequences and
      oligomeric structure being composed of alpha and beta subunits. In contrast
      alphaAI-Pa1 is composed of a single glycopolypeptide with a molecular mass of 35
      kDa, and its N-terminal amino acid sequence resembled that of seed lectins in
      tepary bean and common bean. The information on the two tepary bean alpha-amylase
      inhibitors may be useful not only for providing insight into critical structure
      for the specificity towards different alpha-amylase enzymes but also for
      enhancing insect resistance in crops.

PMID- 11524115
TI  - Characterization of alpha-galactosidases from germinating soybean seed and their
      use for hydrolysis of oligosaccharides.
AB  - Raffinose oligosaccharides (RO) are the major factors responsible for flatulence
      following ingestion of soybean derived products. Removal of RO from seeds or
      soymilk would then have a positive impact on the acceptance of soy-based foods.
      Enzymic hydrolysis of the RO is accomplished by alpha-galactosidase. While the
      content of RO decreases during seed germination, the activity of alpha
      galactosidase increases substantially. Two alpha-galactosidases were isolated
      from germinating seeds by partition in an aqueous two-phase system followed by
      ion-exchange and affinity chromatography. One of the enzyme preparations (P1)
      showed a single protein with M(r) of 33 kDa, and the second (P2) had two proteins
      with M(r) of 31 and 33 kDa. Maximal activities against the synthetic substrate
      rho-nitrophenyl-alpha-D-galactopyranoside (rhoNPGal) were detected at pH 5.0-5.5
      and 45-50 degrees C. Both enzymes were fairly stable at 40 degrees C, but lost
      most of their activities after 30 min at 50 degrees C. The K(m) values for
      hydrolysis of rhoNPGal by the P1 and P2 enzymes were 1.55 and 0.76 mM,
      respectively. The K(m) values determined for hydrolysis of raffinose and
      melibiose by the P2 enzyme were 5.53 and 5.34 mM, respectively and galactose was
      a competitive inhibitor (K(i)=0.65 mM). To different extents, both enzymes were
      sensitive to inhibition by galactose, melibiose, CuSO(4), and SDS. Sucrose and
      beta-mercaptoethanol showed discrete inhibitory effects on both enzymes.

PMID- 11524116
TI  - Effect of the Cnr mutation on carotenoid formation during tomato fruit ripening.
AB  - The characteristic pigmentation of ripe tomato fruit is due to the deposition of
      carotenoid pigments. In tomato, numerous colour mutants exist. The Cnr tomato
      mutant has a colourless, non-ripening phenotype. In this work, carotenoid
      formation in the Cnr mutant has been studied at the biochemical level. The
      carotenoid composition of Ailsa Craig (AC) and Cnr leaves was qualitatively and
      quantitatively similar. However, Cnr fruits had low levels of total carotenoids
      and lacked detectable levels of phytoene and lycopene. The presence of normal
      tocopherols and ubiquinone-9 levels in the ripe Cnr fruits suggested that other
      biosynthetically related isoprenoids were unaffected by the alterations to
      carotenoid biosynthesis. In vitro assays confirmed the virtual absence of
      phytoene synthesis in the ripe Cnr fruit. Extracts from ripe fruit of the Cnr
      mutant also revealed a reduced ability to synthesise the carotenoid precursor
      geranylgeranyl diphosphate (GGPP). These results suggest that besides affecting
      the first committed step in carotenoid biosynthesis (phytoene synthase) the Cnr
      mutation also affects the formation of the isoprenoid precursor (GGPP).

PMID- 11524117
TI  - Effect of culture conditions on the synthesis of vitamin D(3) metabolites in
      Solanum glaucophyllum grown in vitro.
AB  - In cultured Solanum glaucophyllum we have recently described the operation of a
      light-independent pathway of 1alpha,25-dihydroxy-vitamin D(3)
      (1alpha,25(OH)(2)D(3)) biosynthesis which involves similar intermediates as in
      vertebrates. In this work we investigated factors influencing the formation of
      1alpha,25(OH)(2)D(3) and related sterols in S. glaucophyllum grown in vitro in
      darkness. Callus tissue and cells cultured in Murashige and Skoog medium in the
      absence of light were employed. Lipids were extracted with chloroform-methanol.
      The remaining water soluble fraction was incubated with beta-glucosidase to
      release vitamin D(3) compounds from their glycoconjugated derivatives followed by
      organic solvent extraction. Vitamin D(3) derivatives were isolated by Sephadex LH
      20 and high-performance liquid chromatography (HPLC). HPLC or competitive protein
      binding assays with intestine 1alpha,25(OH)(2)D(3) receptor and serum vitamin D
      binding protein were used to quantify the metabolites. The levels of
      1alpha,25(OH)(2)D(3) in calli varied according to the tissue explant origin, e.g.
      stem>leaf>fruit. For all organs, the metabolite was mainly present as free sterol
      (>80% of total). There were larger amounts of 25(OH)D(3) than
      1alpha,25(OH)(2)D(3). It was found that Ca(2+), auxin and kinetin are important
      factors upregulating 1alpha,25(OH)(2)D(3) synthesis in S. glaucophyllum tissue
      and cells. Irradiation with UV light increased vitamin D(3) but not
      1alpha,25(OH)(2)D(3) levels. In agreement with these results, incubation of cells
      with [3H]25(OH)D(3) revealed a low conversion rate to [3H]1alpha,25(OH)(2)D(3).
      The operation of a light-dependent pathway formation of vitamin D(3) coupled to
      higher expression of 25(OH)D(3)-1alpha-hydroxylase may account for the large
      concentrations of 1alpha,25(OH)(2)D(3) normally found in differentiated field
      grown plants.

PMID- 11524118
TI  - Seasonal variation in leaf glucosinolates and insect resistance in two types of
      Barbarea vulgaris ssp. arcuata.
AB  - Leaves from natural populations of Barbarea vulgaris ssp. arcuata (Brassicaceae)
      in Denmark were examined for glucosinolate content and resistance to the crucifer
      specialist flea beetle Phyllotreta nemorum. Two types of the plant (P- and G
      type) could be recognized. Leaves of the G-type contained the glucosinolates
      (only side chains mentioned): (S)-2-hydroxy-2-phenylethyl- (2S), indol-3-ylmethyl
      (4) and in trace amount (R)-2-hydroxy-2-phenylethyl- (2R), 2-phenylethyl- (1)
      and 4-methoxyindol-3-ylmethyl- (5). Leaves of the P-type were dominated by 2R and
      4, and had only trace amounts of 1, 2S, and 5 but contained in addition the
      previously unknown (R)-2-hydroxy-2-(4-hydroxyphenyl)ethyl- (3R). The epimer, (S)
      2-hydroxy-2-(4-hydroxyphenyl)ethyl- (3S) was found in populations believed to be
      hybrids, and in B. orthoceras. 2S, 2R, desulfo 2S,-2R, -3S and -3R were isolated
      and identified by NMR and MS. Acylated glucosinolates or allylglucosinolate were
      not detected in leaves. The glucosinolate content in August was variable, 3-46
      micromol/g dry wt, but was low in most populations, 3-15 micromol/g dry wt. In
      general, the glucosinolate content increased during the autumn, to 35-75
      micromol/g dry wt in November. The G-type was resistant to neonate larvae of
      Phyllotreta nemorum in August and September (survival in 3-day bioassay typically
      0%), and gradually lost the resistance in October and November (survival in 3-day
      bioassay 40-90%), and there was no correlation between glucosinolate content and
      resistance. Neither did glucosinolates explain the difference in resistance
      between the P-type (always susceptible) and the G-type (resistant in the summer
      season).

PMID- 11524119
TI  - Taxonomy of gymnospermae: multivariate analyses of leaf fatty acid composition.
AB  - The fatty acid composition of photosynthetic tissues from 137 species of
      gymnosperms belonging to 14 families was determined by gas chromatography.
      Statistical analysis clearly discriminated four groups. Ginkgoaceae, Cycadaceae,
      Stangeriaceae, Zamiaceae, Sciadopityaceae, Podocarpaceae, Cephalotaxaceae,
      Taxaceae, Ephedraceae and Welwitschiaceae are in the first group, while
      Cupressaceae and Araucariaceae are mainly in the second one. The third and the
      fourth groups composed of Pinaceae species are characterized by the genera Larix,
      and Abies and Cedrus, respectively. Principal component and discriminant analyses
      and divisive hierarchical clustering analysis of the 43 Pinaceae species were
      also performed. A clear-cut separation of the genera Abies, Larix, and Cedrus
      from the other Pinaceae was evidenced. In addition, a mass analysis of the two
      main chloroplastic lipids from 14 gymnosperms was performed. The results point to
      a great originality in gymnosperms since in several species and contrary to the
      angiosperms, the amount of digalactosyldiacylglycerol exceeds that of
      monogalactosyldiacylglycerol.

PMID- 11524120
TI  - Occurrence and characterization of oils rich in gamma-linolenic acid (III): the
      taxonomical value of the fatty acids in Echium (Boraginaceae).
AB  - Fourteen species of the genus Echium (Fam. Boraginaceae) collected in the
      Macaronesia were surveyed in a search for high levels of gamma-linolenic acid
      (GLA, 18:3omega6) in the seed oil. High amounts of this fatty acid were found in
      all of them, ranging from 18.85% (E. pitardii var. pitardii) to 27.42% (E.
      gentianoides) on total seed fatty acids. The GLA content related to total seed
      weight was also significant, ranging from 1.26% (E. handiense) to 8.22% (E.
      gentianoides). In addition, considerable amounts of stearidonic acid (SA,
      18:4omega3) were detected, ranging from 3.78% (E. bonnetii var. bonnetii) to
      8.81% (E. pininana) on total fatty acids. Besides all the perennial species, the
      four herbaceous Echium taxa endemic to the Macaronesia also showed high GLA
      percentages. This is in contrast to the low GLA level found in continental Echium
      species, all of them bearing an herbaceous habit. These results are in good
      agreement with the available genetic data and show the ability of GLA to
      discriminate between Macaronesian and continental Echium species. The analysis of
      five other Macaronesian species belonging to plant families rich in GLA are also
      reported.

PMID- 11524121
TI  - Constituents of Eugenia sandwicensis with potential cancer chemopreventive
      activity.
AB  - A triterpenoid, 3beta-cis-p-coumaroyloxy-2alpha,23-dihydroxyolean-12-en-28-oic
      acid (1), and two natural products, 3beta-trans-p-coumaroyloxy-2alpha,23
      dihydroxyolean-12-en-28-oic acid (2) and 23-trans-p-coumaroyloxy-2alpha,3beta
      dihydroxyolean-12-en-28-oic acid (3), were isolated from a chloroform-soluble
      extract of the stems of Eugenia sandwicensis, along with 10 known compounds. Of
      these compounds, 2 showed significant inhibitory activity (79.2% at 4 microg/ml)
      in a 7,12-dimethylbenz[a]anthracene-induced mouse mammary organ culture assay
      system of relevance to cancer chemoprevention. Gallic acid was isolated as an
      antioxidative constituent of an ethyl acetate-soluble extract of E. sandwicensis
      stems. Isolates 1-3 were characterized on the basis of spectral and chemical
      evidence.

PMID- 11524122
TI  - Stress induced carbazole phytoalexins in Glycosmis species.
AB  - Induced formation of a series of carbazole alkaloids was observed in leaves of
      Glycosmis parviflora and G. pentaphylla after wounding, UV-irradiation, and
      particularly after inoculation with the fungus Botrytis cinerea. Chemical
      variation between different provenances and even individuals of G. parviflora led
      to an accumulation of different derivatives from which three proved to be
      undescribed natural products. Their structures were identified by spectroscopic
      methods and named carbalexins A, B, and C. Bioautographic tests on TLC plates
      with Cladosporium herbarum exhibited strong antifungal activity for the new
      carbalexins as well as for the already known 2-hydroxy-3-methylcarbazole, but
      only weak effects for the pyranocarbazole glycoborinine. Detailed experiments
      with marked infection areas confirmed the restricted accumulation of carbazole
      derivatives which could not be detected in non-infected areas of the same leaf.
      Apart from carbazoles, in some individuals of G. parviflora an additional
      accumulation of the pyranoquinolones flindersine and methylflindersine was
      induced, which supports the already previously discussed biogenetic connections
      between carbazoles and prenylated quinolones.

PMID- 11524123
TI  - Structure and characterization of the crown gall opines heliopine, vitopine and
      rideopine.
AB  - The crown gall opines heliopine from tumors induced by octopine type
      Agrobacterium tumefaciens strains A6, A136(pTiB6-806), E9, A652 and 1590-1 and
      vitopine from tumor induced by grapevine strains S4 and T2 are identical to
      synthetic N2-(1'R-carboxyethyl)-L-glutamine. Tumors produced by strains S4 and T2
      do not contain octopine or lysopine, but they do contain heliopine and the new
      opine rideopine identified as N-(4'-aminobutyl)-D-glutamic acid. Grapevine
      strains S4 and T2 grow normally on tumor heliopine or synthetic heliopine and on
      tumor and synthetic rideopine as well as on rideopine lactam as sole carbon
      source. While octopine strains A6 and A136(pTiB6-806) do not grow on heliopine,
      mutant colonies do appear after a few weeks. Heliopine catabolism by octopine
      strains is not induced by octopine.

PMID- 11524124
TI  - The antioxidant activity of aqueous spinach extract: chemical identification of
      active fractions.
AB  - In previous studies we have elucidated the presence of powerful, natural
      antioxidants (NAO) in water extracts of spinach leaves and demonstrated their
      biological activity in both in vitro and in vivo systems. In the present study,
      the chemical identity of several of these antioxidant components is presented.
      Spinach leaves were extracted with water and the 20,000 g supernatant which
      contained the antioxidant activity was extracted with a water:acetone (1:9)
      solution. The 20,000 g supernatant obtained was further purified on reverse phase
      HPLC using C-8 semi-preparative column. Elution with 0.1% TFA resulted in five
      hydrophilic peaks. Elution with acetonitrile in TFA resulted in seven additional
      hydrophobic peaks. All the peaks were detected at 250 nm. All the fractions
      obtained showed antioxidant activity when tested using three different assays.
      Based on 1H and 13C NMR spectroscopy four of the hydrophobic fractions were
      identified as glucuronic acid derivatives of flavonoids and three additional
      fractions as trans and cis isomers of p-coumaric acid and others as meso
      tartarate derivatives of p-coumaric acid. The present study demonstrates for the
      first time the presence of both flavonoids and p-coumaric acid derivatives as
      antioxidant components of the aqueous extract of spinach leaves.

PMID- 11524125
TI  - Isolation of an anti-HIV diprenylated bibenzyl from Glycyrrhiza lepidota.
AB  - The organic soluble extract from the leaves of Glycyrrhiza lepidota showed
      moderate activity in the US National Cancer Institute in vitro anti-HIV-1
      bioassay. Chromatographic separation of this extract resulted in the
      identification of a new diprenylated bibenzyl as the compound responsible for the
      observed anti-viral activity. Extensive spectroscopic experiments provide the
      complete 1H NMR and 13C NMR spectral assignments to support the proposed
      structure. Known compounds glepidotin B and glepidotin A were also isolated from
      the extract and shown to be inactive in the anti-viral assay.

PMID- 11524126
TI  - Betalains of Celosia argentea.
AB  - The betalains of yellow, orange and red inflorescences of common cockscomb
      (Celosia argentea var. cristata) were compared and proved to be qualitatively
      identical to those of feathered amaranth (Celosia argentea var. plumosa). In
      addition to the known compounds amaranthin and betalamic acid, the structures of
      three yellow pigments were elucidated to be immonium conjugates of betalamic acid
      with dopamine, 3-methoxytyramine and (S)-tryptophan by various spectroscopic
      techniques and comparison to synthesized reference compounds; the latter two are
      new to plants. Among the betacyanins occurring in yellow inflorescences in trace
      amounts, the presence of 2-descarboxy-betanidin, a dopamine-derived betacyanin,
      has been ascertained. The detection of high dopamine concentration may be of
      toxicological relevance in use of yellow inflorescences as a vegetable and in
      traditional Chinese medicine, common uses for the red inflorescences of common
      cockscomb.

PMID- 11524127
TI  - Acylated flavone C-glycosides from Cucumis sativus.
AB  - Leaves of Cucumis sativus plants treated with silicon and infected with
      Sphaerotheca fuliginea yielded five new acylated flavone C-glycosides identified
      as isovitexin 2"-O-(6"'-(E)-p-coumaroyl)glucoside (6), isovitexin 2"-O-(6"'-(E)-p
      coumaroyl)glucoside-4'-O-glucoside (7), isovitexin 2"-O-(6"'-(E)
      feruloyl)glucoside-4'-O-glucoside (11), isoscoparin 2"-O-(6"'-(E)-p
      coumaroyl)glucoside (9), and isoscoparin 2"-O-(6"'-(E)-feruloyl)glucoside-4'-O
      glucoside (12). The known flavone-glycosides isovitexin (1), saponarin (2),
      saponarin 4'-O-glucoside (3), vicenin-2 (4), apigenin 7-O-(6"-O-p
      coumaroylglucoside) (5), isovitexin 2"-O-(6"'-(E)-feruloyl)glucoside (8) and
      isoscoparin 2"-O-(6"'-(E)-feruloyl)glucoside (10), were also identified in this
      plant material.

PMID- 11524128
TI  - 3(2H)-Benzofuranones and chromanes from liquid cultures of the mycoparasitic
      fungus Coniothyrium minitans.
AB  - Two 3(2H)-benzofuranones and three chromanes were isolated from the mycoparasitic
      fungus Coniothyrium minitans. Their structures and absolute stereochemistry were
      determined by spectroscopic methods.

PMID- 11524129
TI  - Cytotoxic 7,20-epoxy ent-kauranoids from Isodon xerophilus.
AB  - Four 7,20-epoxy ent-kaurane diterpenoids, xerophilusins G (1) and I-K (2-4), were
      isolated from the leaves of Isodon xerophilus, along with four known ones,
      enanderianin C (5), rosthorin A (6), longikaurin B (7), and rabdoternin D (8).
      Their structures were determined primarily using NMR spectroscopic techniques.
      The structure and stereochemistry of 3 were confirmed by X-ray crystallography.
      Compounds 4 and 7 exhibited broad cytotoxicity against four kinds of human tumor
      cells (K562, HL-60, HCT, and MKN-28 cells) in the range of 2.23-15.35 and 0.30
      8.61 microg/ml, respectively.

PMID- 11524130
TI  - Quorum-sensing in Gram-negative bacteria.
AB  - It has become increasingly and widely recognised that bacteria do not exist as
      solitary cells, but are colonial organisms that exploit elaborate systems of
      intercellular communication to facilitate their adaptation to changing
      environmental conditions. The languages by which bacteria communicate take the
      form of chemical signals, excreted from the cells, which can elicit profound
      physiological changes. Many types of signalling molecules, which regulate diverse
      phenotypes across distant genera, have been described. The most common signalling
      molecules found in Gram-negative bacteria are N-acyl derivatives of homoserine
      lactone (acyl HSLs). Modulation of the physiological processes controlled by acyl
      HSLs (and, indeed, many of the non-acyl HSL-mediated systems) occurs in a cell
      density- and growth phase-dependent manner. Therefore, the term 'quorum-sensing'
      has been coined to describe this ability of bacteria to monitor cell density
      before expressing a phenotype. In this paper, we review the current state of
      research concerning acyl HSL-mediated quorum-sensing. We also describe two non
      acyl HSL-based systems utilised by the phytopathogens Ralstonia solanacearum and
      Xanthomonas campestris.

PMID- 11524131
TI  - The tripartite ATP-independent periplasmic (TRAP) transporters of bacteria and
      archaea.
AB  - Until recently, extracytoplasmic solute receptor (ESR)-dependent uptake systems
      were invariably found to possess a conserved ATP-binding protein (the ATP-binding
      cassette protein or ABC protein), which couples ATP hydrolysis to the
      translocation of the solute across the cytoplasmic membrane. While it is clear
      that this class of ABC transporter is ubiquitous in prokaryotes, it is now firmly
      established that other, unrelated types of membrane transport systems exist which
      also have ESR components. These systems have been designated tripartite ATP
      independent periplasmic (TRAP) transporters, and they form a distinct class of
      ESR-dependent secondary transporters where the driving force for solute
      accumulation is an electrochemical ion gradient and not ATP hydrolysis.
      Currently, the most well characterised TRAP transporter at the functional and
      molecular level is the high-affinity C4-dicarboxylate transport (Dct) system from
      Rhodobacter capsulatus. This consists of three proteins; an ESR (DctP) and small
      (DctQ) and large (DctM) integral membrane proteins. The characteristics of this
      system are discussed in detail. Homologues of the R. capsulatus DctPQM proteins
      are present in a diverse range of prokaryotes, both bacteria and archaea, but not
      in eukaryotes. The deduced structures and possible functions of these homologous
      systems are described. In addition to the DctP family, other types of ESRs can be
      associated with TRAP transporters. A conserved family of immunogenic
      extracytoplasmic proteins is shown to be invariably associated with TRAP systems
      that contain a large DctQM fusion protein. All of the currently known archaeal
      systems are of this type. It is concluded that TRAP transporters are a widespread
      and ancient type of solute uptake system that transport a potentially diverse
      range of solutes and most likely evolved by the addition of auxiliary proteins to
      a single secondary transporter.

PMID- 11524132
TI  - Genomic style of proteins: concepts, methods and analyses of ribosomal proteins
      from 16 microbial species.
AB  - We have introduced the concept of genomic 'style' of proteins. By style we
      understand those properties of a large set of proteins which are specific to the
      genome of one species (species primary-self) and different from the genome of
      another species (species contrasted-self). To characterise the style, we took
      advantage of the frequencies of amino acids and dipeptides present in non
      identical segments of the complete set of orthologous ribosomal proteins encoded
      by 16 microbial species. We confirm the dependence of the overall amino acid
      composition on the genomic (G+C) content, and introduce a rectification procedure
      making it possible to extricate appropriate species-specific characteristics,
      which are no longer related to this content. The rectified frequencies are used
      to calculate inter-species distance matrices, and to build genomic evolutionary
      trees. Remarkably, the phylograms derived from the frequencies of non-identical
      residues in proteins closely resemble the classical phylograms based upon the
      conservation of identical residues in ribosomal RNAs. We believe that the concept
      of genomic style of proteins can be a useful tool for the study of evolution.

PMID- 11524133
TI  - Translocation of proteins across the cell envelope of Gram-positive bacteria.
AB  - In contrast to Gram-negative bacteria, secretory proteins of Gram-positive
      bacteria only need to traverse a single membrane to enter the extracellular
      environment. For this reason, Gram-positive bacteria (e.g. various Bacillus
      species) are often used in industry for the commercial production of
      extracellular proteins that can be produced in yields of several grams per liter
      culture medium. The central components of the main protein translocation system
      (Sec system) of Gram-negative and Gram-positive bacteria show a high degree of
      conservation, suggesting similar functions and working mechanisms. Despite this
      fact, several differences can be identified such as the absence of a clear
      homolog of the secretion-specific chaperone SecB in Gram-positive bacteria. The
      now available detailed insight into the organization of the Gram-positive protein
      secretion system and how it differs from the well-characterized system of
      Escherichia coli may in the future facilitate the exploitation of these organisms
      in the high level production of heterologous proteins which, so far, is sometimes
      very inefficient due to one or more bottlenecks in the secretion pathway. In this
      review, we summarize the current knowledge on the various steps of the protein
      secretion pathway of Gram-positive bacteria with emphasis on Bacillus subtilis,
      which during the last decade, has arisen as a model system for the study of
      protein secretion in this industrially important class of microorganisms.

PMID- 11524134
TI  - Classification and phylogeny of hydrogenases.
AB  - Hydrogenases (H2ases) catalyze the reversible oxidation of molecular hydrogen and
      play a central role in microbial energy metabolism. Most of these enzymes are
      found in Archaea and Bacteria, but a few are present in Eucarya as well. They can
      be distributed into three classes: the [Fe]-H2ases, the [NiFe]-H2ases, and the
      metal-free H2ases. The vast majority of known H2ases belong to the first two
      classes, and over 100 of these enzymes have been characterized genetically and/or
      biochemically. Compelling evidence from sequences and structures indicates that
      the [NiFe]- and [Fe]-H2ases are phylogenetically distinct classes of proteins.
      The catalytic core of the [NiFe]-H2ases is a heterodimeric protein, although
      additional subunits are present in many of these enzymes. Functional classes of
      [NiFe]-H2ases have been defined, and they are consistent with categories defined
      by sequence similarity of the catalytic subunits. The catalytic core of the [Fe]
      H2ases is a ca. 350-residue domain that accommodates the active site (H-cluster).
      A few monomeric [Fe]-H2ases are barely larger than the H-cluster domain. Many
      others are monomeric as well, but possess additional domains that contain redox
      centers, mostly iron-sulfur. Some [Fe]-H2ases are oligomeric. The modular
      structure of H2ases is strikingly illustrated in recently unveiled sequences and
      structures. It is also remarkable that most of the accessory domains and subunits
      of H2ases have counterparts in other redox complexes, in particular NADH
      ubiquinone oxidoreductase (Complex I) of respiratory chains. Microbial genome
      sequences are bringing forth a significant body of additional H2ase sequence data
      and contribute to the understanding of H2ase distribution and evolution.
      Altogether, the available data suggest that [Fe]-H2ases are restricted to
      Bacteria and Eucarya, while [NiFe]-H2ases, with one possible exception, seem to
      be present only in Archaea and Bacteria. H2ase processing and maturation involve
      the products of several genes which have been identified and are currently being
      characterized in the case of the [NiFe]-H2ases. In contrast, near to nothing is
      known regarding the maturation of the [Fe]-H2ases. Inspection of the currently
      available genome sequences suggests that the [NiFe]-H2ase maturation proteins
      have no similar counterparts in the genomes of organisms possessing [Fe]-H2ases
      only. This observation, if confirmed, would be consistent with the phylogenetic
      distinctiveness of the two classes of H2ases. Sequence alignments of catalytic
      subunits of H2ases have been implemented to construct phylogenetic trees that
      were found to be consistent, in the main, with trees derived from other data. On
      the basis of the comparisons performed and discussed here, proposals are made to
      simplify and rationalize the nomenclature of H2ase-encoding genes.

PMID- 11524135
TI  - Interactions between cadmium and zinc in the organism.
AB  - It is well known that many toxic effects of cadmium (Cd) action result from
      interactions with essential elements, including zinc (Zn). These interactions can
      take place at different stages of absorption, distribution in the organism and
      excretion of both metals and at the stage of Zn biological functions. Exposure to
      Cd leads to disturbance in Zn in the organism on the one hand, while dietary Zn
      intake has an important effect on Cd absorption, accumulation and toxicity on the
      other. The Zn status of the body is important in relation to development of Cd
      toxicity. Numerous data show that increased Zn supply may reduce Cd absorption
      and accumulation and prevent or reduce the adverse actions of Cd, whereas Zn
      deficiency can intensify Cd accumulation and toxicity. In this review, the
      interactions between these two trace elements in humans and animals are discussed
      on the basis of the available literature and our own results, against the
      background of general population exposure to Cd and common nutritional deficiency
      of Zn.

PMID- 11524136
TI  - Effect of onion consumption by rats on hepatic drug-metabolizing enzymes.
AB  - Fruits and vegetables or their natural constituents which increase detoxication
      enzymes and/or reduce activating enzymes are considered as good candidates to
      prevent chemically-induced carcinogenesis. In this study, rats were fed a diet
      supplemented with 20% onion powder for 9 days. Several cytochrome P450 (CYP)s
      enzymes (CYP 1A, 2B, 2E1, 3A), which are involved in carcinogen activation, were
      determined by measuring their enzyme activities using specific substrates. In
      addition, phase II enzymes activities such as UDP-glucuronosyltransferase (UGT)
      and glutathione S-transferase (GST), involved in detoxication of carcinogens,
      were measured. Protein levels of CYPs and GST A1/A2, A3/A5, Ml, M2 and P1 were
      measured using antibodies in Western blots. Consumption of onion induced CYP 1A
      and CYP 2B activities while it decreased CYP 2E1 activity. This later
      modification was accompanied by a decrease of CYP 2E1 levels. The same dietary
      treatment caused a slight increase of the total GST activity. The relative
      proportions of GST subunits were modified. GST Al/A2 subunits were increased
      while GST A3/A5 and GST M2 subunits were decreased and GST M1 and P1 were not
      modified. Onion consumption also increased p-nitrophenol UGT activity. Taken
      together, these results suggest that the decrease of CYP 2E1 and the increase of
      phase II enzymes by onion can afford protection against some carcinogens, while
      the decrease of some GST subunits could increase the genotoxic effects of other
      chemicals. The modulating effect of onion could be ascribed to alk(en)yl
      polysulphides and/or glycosides of flavonols, which were identified in the onion
      powder.

PMID- 11524137
TI  - Modulation of glyoxalase, glutathione S-transferase and antioxidant enzymes in
      the liver, spleen and erythrocytes of mice by dietary administration of fenugreek
      seeds.
AB  - There is a growing interest in understanding the biological effect of time-tested
      folk medicinal plants. In the present work, the effect of dietary administration
      of fenugreek seeds on the glyoxalase system and antioxidant enzymes as well as
      levels of glutathione (GSH) have been examined in different tissues of mice.
      Swiss albino mice were fed with diet containing powdered fenugreek for 4 weeks.
      The mode and magnitude of effect was found to depend on the dose of fenugreek and
      type of tissue. The diet containing 1 and 2% of fenugreek enhanced the specific
      activity of gly I, whereas 5 and 10% inhibited its activity in the liver.
      However, on the other hand, the specific activity of gly II decreased
      continuously with dose. Dietary administration of fenugreek seeds resulted in an
      increase of GSH levels and the glutathione S-transferase (GST) activity in the
      liver. Fenugreek (1 and 2%) showed no appreciable change in superoxide dismutase
      (SOD) and catalase. However, 5 and 10% doses of fenugreek supplementation
      inhibited their activities. In the case of spleen, a significant change in gly I
      was observed only at 10% fenugreek. In addition, a significant increase was also
      observed with GSH levels. Fenugreek treatment up to 5% showed a small but
      consistent increase in erythrocytes. In the case of GST, the activity enhanced
      with dose. Significant elevation of catalase activity was observed with a 10%
      dose of fenugreek. The significance and relevance of these findings are suggested
      in relation to mechanistic aspects.

PMID- 11524138
TI  - Lack of effect of furfural on unscheduled DNA synthesis in the in vivo rat and
      mouse hepatocyte DNA repair assays and in precision-cut human liver slices.
AB  - The ability of furfural to induce unscheduled DNA synthesis (UDS) in hepatocytes
      of male and female B6C3F(1) mice and male F344 rats after in vivo administration
      and in vitro in precision-cut human liver slices has been studied. Preliminary
      toxicity studies established the maximum tolerated dose (MTD) of furfural to be
      320 and 50 mg/kg in the mouse and rat, respectively. Furfural was dosed by gavage
      at levels of 0 (control), 50, 175 and 320 mg/kg to male and female mice and 0, 5,
      16.7 and 50 mg/kg to male rats. Hepatocytes were isolated by liver perfusion
      either 2-4 h or 12-16 h after treatment, cultured in medium containing
      [3H]thymidine for 4 h and assessed for UDS by grain counting of autoradiographs.
      Furfural treatment did not produce any statistically significant increase or any
      dose-related effects on UDS in mouse and rat hepatocytes either 2-4 h or 12-16 h
      after dosing. In contrast, UDS was markedly induced in mice and rats 2-4 h after
      treatment with 20 mg/kg dimethylnitrosamine and 12-16 h after treatment of mice
      and rats with 200 mg/kg o-aminoazotoluene and 50 mg/kg 2-acetylaminofluorene (2
      AAF), respectively. Precision-cut human liver slices from four donors were
      cultured for 24 h in medium containing [3H]thymidine and 0-10 mM furfural. Small
      increases in the net grain count (i.e. nuclear grain count less mean cytoplasmic
      grain count) observed with 2-10 mM furfural were not due to any increase in the
      nuclear grain count. Rather, it was the result of concentration-dependent
      decreases in the mean cytoplasmic grain counts and to a lesser extent in nuclear
      grain counts, due to furfural-induced cytotoxicity. In contrast, marked increases
      in UDS (both net grain and nuclear grain counts) were observed in human liver
      slices treated with 0.02 and 0.05 mM 2-AAF, 0.002 and 0.02 mM aflatoxin B(1) and
      0.005 and 0.05 mM 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine. This study
      demonstrates that furfural does not induce UDS in the hepatocytes of male and
      female B6C3F(1) mice and male F344 rats after oral treatment at doses up to the
      MTDs. Moreover, human liver slice studies suggest that furfural is also not a
      genotoxic agent in human liver.

PMID- 11524139
TI  - Effects of the calcium channel blocker verapamil and sulphydryl reducing agent
      dithiothreitol on atractyloside toxicity in precision-cut rat renal cortical and
      liver slices.
AB  - The effects of dithiothreitol (DTT), a sulfhydryl-containing agent and verapamil
      (VRP), a calcium channel blocker as possible cytoprotectants against the
      atractyloside-induced toxicity were characterized in rat kidney and liver slices
      in vitro using multiple markers of toxicity. Precision-cut slices (200 microM
      thick) were either incubated with atractyloside (2 mM) or initially preincubated
      with either DTT (5 mM) or VRP (100 microM) for 30 min followed by exposure to
      atractyloside (2 mM) for 3 h at 37 degrees C on a rocker platform rotated at
      approximately 3 rpm. All of the toxicity parameters were sensitive to exposure to
      atractyloside, but treatment with DTT or VRP alone did not provide any indication
      of damage to the tissues. Preincubation of slices containing either DTT or VRP
      for 30 min provided total protection against atractyloside-induced increase in
      LDH leakage in both kidney and liver slices. Increased induction of lipid
      peroxidation by atractyloside in liver slices was completely abolished by DTT and
      VRP. Both DTT and VRP provided partial protection against atractyloside-induced
      inhibition of gluconeogenesis in both kidney and liver slices. Atractyloside
      induced ATP depletion in both kidney and liver slices was partially abolished by
      VRP but not DTT. The significant depletion of GSH in the kidney slices by
      atractyloside was completely reversed by DTT only, while VRP alone reversed the
      same process in liver slices. Decreased MTT reductive capacity and significant
      increase in ALT leakage caused by atractyloside in liver slices was partially
      reversed. Complete protection was achieved with both DTT and VRP against
      atractyloside-induced inhibition of PAH uptake in kidney slices. These findings
      suggest that both DTT and VRP exert cytoprotective effects in atractyloside
      induced biochemical perturbation, effects that differ in liver and kidney. The
      effect of these agents on atractyloside has provided us with a further
      understanding of the molecular mechanism of its action.

PMID- 11524140
TI  - Assessment of embryo/fetotoxicity and teratogenicity of azadirachtin in rats.
AB  - To evaluate the potential effect of exposure to azadirachtin technical 12%
      throughout major organogenesis, rats were fed orally with 500, 1000 and 1500
      mg/kg/day azadirachtin on gestation days 6-15 and examined for evidence of
      embryo/fetotoxicity and teratogenic effects. Technical azadirachtin at different
      doses did not produce any significant adverse effects in reproductive parameters.
      Significant embryo/fetotoxic effects were not observed at tested dose levels as
      evidenced by total number of implantations, post-implantation loss and fetal
      weight. There were no major malformations, while some minor variants found in
      high doses were not compound or dose related. The absence of anomalies in fetal
      gross, visceral morphology and skeleton suggests that technical azadirachtin is
      not teratogenic in rats at the doses tested.

PMID- 11524142
TI  - Effect of chronic protein restriction on motor co-ordination and brain
      neurotransmitters in albino rats.
AB  - In this study we evaluated the motor co-ordination in Wistar strain albino rats
      that were maintained on a protein-restricted diet for a period of 1 year
      immediately after the weaning period, by substituting 75% of the normal diet with
      a carbohydrate-rich diet deficient in protein, for a period of 1 year immediately
      after the weaning period. This type of chronic protein restriction caused
      disturbances in motor co-ordination. It also caused a significant reduction in
      the basal levels of dopamine, norepinephrine, epinephrine and serotonin along
      with their metabolites homovanillic acid (HVA), vanillyl mandelic acid (VMA) and
      5-hydroxy indoleacetic acid (5HIAA) and precursor L-dopa in the corpus striatum
      and cerebellum. Changes in these neurotransmitters could have caused altered co
      ordination in the protein-restricted animals.

PMID- 11524141
TI  - Possible role of metal redistribution, hepatotoxicity and oxidative stress in
      chelating agents induced hepatic and renal metallothionein in rats.
AB  - A study was planned to investigate possible role of oxidative stress, hepato- and
      nephrotoxicity and essential metal redistribution following administration of
      amino and thiol chelating agents on hepatic and renal metallothionein (MT) and
      the levels of some metalloenzymes in male rats. Animals were administered 50
      mg/kg, intraperitoneally, twice daily for 15 consecutive days; a dose of three
      amino and four thiol chelators and were sacrificed 24 h after the last dose. The
      results indicate no evidence of oxidative stress in hepatic and renal tissues of
      rats administered thiol and amino chelators, except for some marginal changes in
      the animals treated with calcium disodium ethylenediaminetetraacetic acid (EDTA)
      and D-penicillamine (DPA). Redistribution of essential metal (particularly zinc),
      hepato- and nephrotoxicity seems to play a significant role in influencing the MT
      induction by amino chelators. Redistribution of essential metals may also be
      playing a significant role in a number of metalloenzymes, especially by amino
      chelators compared to thiol chelators. It can thus be concluded that toxic
      effects of chelating agents, including metal redistribution and hepatotoxicity,
      might be playing a crucial role in the metallothionein induction.

PMID- 11524143
TI  - Gene expression profiling of the tau mutant (P301L) transgenic mouse brain.
AB  - To provide a global analysis of the influence of Tau neuropathology at molecular
      level, we used cDNA arrays representing 8832 genes to determine the mRNA
      expression profile in transgenic mice expressing the most common frontotemporal
      dementia and parkinsonism linked to chromosome 17 (FTDP-17) Tau mutation (P301L)
      (Nat. Genet. (2000) 402). Genes whose expression is associated with development
      of neurofibrillary tangles and neuron loss in P301L mice with motor and
      behavioral deficits were identified. The data suggest that a major mechanism
      underlying P301LTau neurodegeneration primarily involved altered expression of
      genes contributing to inhibition of apoptosis and intracellular transport. We
      propose that the expression of mutated P301L may lead to select altered
      expression of genes which may cause neurodegeneration in FTDP-17.

PMID- 11524144
TI  - Clonal composition of human adamantinomatous craniopharyngiomas and somatic
      mutation analyses of the patched (PTCH), Gsalpha and Gi2alpha genes.
AB  - Craniopharyngioma is the most common childhood tumor and thought to arise from
      embryonic remnants of Rathke's pouch. The paucity of published data on the
      molecular basis of these tumors prompted us to examine 22 adamantinomatous
      craniopharyngiomas looking for genetic abnormalities. Using the X-linked
      polymorphic androgen receptor gene as a tool for X-chromosome inactivating
      analysis, we found that a subset of craniopharyngiomas are monoclonal and
      therefore are probably due to acquired somatic genetic defects. Thus, we
      investigated these tumours for mutations within three candidate genes, Gsalpha,
      Gi2alpha and patched (PTCH). Using single stranded conformational polymorphism
      (SSCP), denaturing gradient gel electrophoresis and direct sequencing, the
      presence of somatic mutations in these genes could not be demonstrated in any
      tumor. Our data indicate that a subset of craniopharyngiomas are monoclonal and
      the mutations in the PTCH, Gsalpha, and Gi2alpha contribute little if any to
      craniopharyngioma development.

PMID- 11524145
TI  - A region of the rat N-methyl-D-aspartate receptor 2A subunit that is sufficient
      for potentiation by phorbol esters.
AB  - N-methyl-D-aspartate (NMDA) receptors are modulated by protein kinase C (PKC) in
      vivo and in heterologous expression systems. In heterologous expression systems,
      PKC-mediated modulation is subunit specific with NR2A-containing receptors being
      potentiated by phorbol 12-myristate 13-acetate (PMA), while NR2C-containing
      receptors are inhibited or unaffected. In the present study we have produced
      chimeric receptors containing NR2A and NR2C to define the components of NR2A
      which are sufficient for potentiation by PMA. Amino acids 1105-1400 of NR2A
      placed onto the C-terminus of NR2C at amino acid 1102 was the minimum region
      sufficient for producing a PMA-stimulated receptor. This suggests that this
      region contains structural determinants for PKC-mediated potentiation of NR2A
      receptors.

PMID- 11524146
TI  - Temporal and spatial patterns of DNA fragmentation following focally or
      systemically-evoked status epilepticus in rats.
AB  - Status epilepticus (SE) triggers neuronal degeneration comprised of both necrotic
      and apoptotic components. Here we determined whether internucleosomal DNA
      fragmentation reflects the severity of SE-induced neuronal damage. We utilized
      both a systemic (kainic acid) and a focally-induced model of SE in rats. DNA
      fragmentation was analyzed in rhinal cortex and hippocampus at various time
      points following SE episodes of varying durations (30-120 min). Radioactively
      labeled DNA fragments were analyzed by agarose gel electrophoresis and quantified
      by liquid scintillation counting. The spatial and temporal characteristics of the
      SE-evoked DNA fragmentation indicated that this marker of apoptosis appears as
      early as 8 h after SE and reaches peak expression at 48 h. This method permitted
      us to quantitatively monitor the evolution of the apoptotic component of cell
      death over the acute post-injury period (8-72 h). Moreover, in both models of SE,
      the DNA fragmentation varied directly as a linear function of the duration of SE
      between 30 and 120 min suggesting that this marker should be highly responsive to
      neuroprotective intervention.

PMID- 11524147
TI  - Novel polymorphism in the 5'-upstream region of the human 5-HT6 receptor gene and
      schizophrenia.
AB  - The localization of 5-hydroxytryptamine6 (5-HT6) receptor in the limbic and
      cortical regions, and the high affinity of atypical antipsychotic drugs such as
      clozapine for the receptor, suggest the possible involvement of the receptor in
      the pathogenesis of schizophrenia. In this study, we searched systematically for
      polymorphisms in the 5'-upstream region of the human 5-HT6 receptor gene. We
      identified a trinucleotide repeat polymorphism, (GCC)2/3, at a nucleotide
      position between -1093 and -1085 bp upstream from the translation start site.
      Subsequent case-control association study did not demonstrate significant
      differences of genotype and allele frequency between 206 controls and 246
      patients with schizophrenia. Our results suggest that the 5-HT6 receptor gene
      polymorphism does not confer increased susceptibility to schizophrenia.

PMID- 11524148
TI  - Reduction of cortical amyloid beta levels in guinea pig brain after systemic
      administration of physostigmine.
AB  - Overproduction of the peptide amyloid beta (Abeta) is thought to be a critical
      pathogenetic event in Alzheimer's disease (AD). Decreasing A production may
      therefore slow or halt the progression of AD. In vitro work has indicated that
      cholinergic muscarinic receptor agonists may reduce cellular production of Abeta.
      Here we show that systemic administration of physostigmine, an
      acetylcholinesterase inhibitor, lowers Abeta levels in vivo. Guinea pigs treated
      for 10 days with s.c. physostigmine had levels of cortical AbetaN-40 and N-42
      which were 57% and 72%, respectively, of those in control animals. Levels of
      cortical beta-amyloid precursor protein were not significantly affected by drug
      treatment. These results suggest that cholinergic therapy may affect the course
      of AD by limiting Abeta accumulation.

PMID- 11524149
TI  - Region-specific decrease in 5-HT1A and 5-HT1B binding sites after intra
      hippocampal ibotenic acid injections in the rat.
AB  - The cellular location of 5-HT1A and 5-HT1B binding sites in the hippocampus was
      investigated using a stereotaxic unilateral lesion of the CA1 field by ibotenic
      acid, followed by autoradiography on brain sections with the specific ligands
      [3H]8-OH-DPAT and S-CM-G[125I]TNH2, respectively. As compared to the
      contralateral side of the lesion, the ipsilateral side exhibited a decrease in
      the density of 5-HT1A binding sites in the strata oriens and radiatum of CA1, and
      of 5-HT1B binding sites in the dorsal subiculum and stratum oriens of CA1. The
      results demonstrate that 5-HT1A binding sites are located on dendrites whereas 5
      HT1B binding sites are located on axon terminals of CA1 pyramidal cells.

PMID- 11524150
TI  - The changes in the expressions of gamma-aminobutyric acid transporters in the
      gerbil hippocampal complex following spontaneous seizure.
AB  - To identify the roles of gamma-aminobutyric acid (GABA) transporter in
      epileptogenesis and the recovery mechanisms in spontaneous seizure, a
      chronological and comparative analysis of GABA transporters (GAT) expression was
      conducted. GAT-1 immunoreactivity was more strongly detected in the pre-seizure
      group of seizure sensitive (SS) gerbils than that seen in the seizure resistant
      group. 30 min postictal, the density of GAT-1 immunoreactivity was significantly
      decreased in the hippocampal complex, as compared to pre-seizure group. 12 h
      after seizure on-set, the GAT immunodensity recovered to the pre-seizure level.
      Following the onset of seizure, GAT-3 immunoreactivity remained unchanged. These
      results suggest that the increase of GAT-1 expression in the SS gerbil
      hippocampus may affect epileptogenesis in this animal, and the alteration of
      immunoreactivity following seizure may be compensatory responses to modulate
      seizure activity.

PMID- 11524151
TI  - Visual attention to words of native versus later acquired languages: a
      magnetoencephalographic study in humans.
AB  - We recorded evoked magnetic fields while short words were visually presented in
      different languages with an oddball paradigm. The task was to count how many
      words were in a target language when most of the words were in another language
      and there were also non-target deviants in a third language. When native words
      (Finnish) were targets, they evoked a selection response at the latency of 300
      600 ms. However, when the task was to count non-native words among native
      standards, in addition to the targets, also the non-target foreign words evoked
      the selection response. These results may reflect differences in the selection
      process for native versus non-native words brought about by different proficiency
      levels of the languages.

PMID- 11524152
TI  - The blink reflex and the corneal reflex are followed by cortical activity
      resembling the nociceptive potentials induced by trigeminal laser stimulation in
      man.
AB  - Laser stimulation of the supraorbital regions evokes brain potentials (LEPs)
      related to trigeminal nociception. The aim of this study was to record the R2
      component of the blink reflex and the corneal reflex in 20 normal subjects,
      comparing the scalp activity following these reflexes with the nociceptive
      potentials evoked by CO2 laser stimulation of supraorbital regions. Cortical and
      muscular reflexes evoked by stimulation of the first trigeminal branch were
      recorded simultaneously. The R2 component of the blink reflex and the corneal
      reflex were followed by two cortical peaks, which resembled morphologically N-P
      waves of LEPs. The two peaks demonstrated a difference in latency of
      approximately 40 ms, which is consistent with activation time of nociception.
      This finding suggests that these reflexes are induced by activation of small pain
      related fibers.

PMID- 11524153
TI  - Dipole orientation differs between high frequency oscillations and N20m current
      sources in human somatosensory evoked magnetic fields to median nerve
      stimulation.
AB  - The dipole orientation of equivalent current source for the high frequency
      oscillations (HFOs) above 300 Hz and that for the underlying N20m were compared.
      Somatic magnetic fields were recorded over the left hand somatosensory area to
      right median nerve stimulation at the wrist with a wide-bandpass (0.1-2000 Hz).
      The HFOs and underlying N20m were extracted by digital filtering of 300-900 Hz
      and 1-300 Hz, respectively. We found that the orientation of the HFOs and
      underlying N20m current sources differs and that the HFO source orientation shows
      a more divergent pattern than the N20m. These results suggest that the
      somatosensory HFOs are not generated from the pyramidal cell population in area
      3b which produces the underlying N20m and that they may reflect activities of the
      non-pyramidal neuron population.

PMID- 11524154
TI  - Lysyl oxidase, the extracellular matrix-forming enzyme, in rat brain injury
      sites.
AB  - Lysyl oxidase is an extracellular enzyme that catalyzes cross-linkages of
      extracellular matrix proteins. We hypothesized that this enzyme is secreted by
      cells attracted to central nervous system injury sites and is involved in
      extracellular matrix modulation and in scar formation. Specific antibodies for
      immunohistochemistry and enzyme activity measurements were used to detect the
      presence of lysyl oxidase after longitudinal knife cuts in adult rat forebrain.
      Immunoreactivity was observed within the core of injury sites from 1 and up to 30
      days postoperative, with less staining at 2 and 5 days, and was not associated
      with glial fibrillary acidic protein-positive astrocytes. Enzyme activity
      increased transiently in injury site regions with a peak (200% of control) at 10
      days postoperative. These results are the first to provide evidence for a time
      dependent appearance of active extracellular lysyl oxidase in brain injury sites.
      They imply that enzyme molecules are synthesized and secreted by cells attracted
      to brain injury sites and participate in extracellular matrix modulation.

PMID- 11524155
TI  - Bisphenol-A differently affects estrogen receptors-alpha in estrous-cycling and
      lactating female rats.
AB  - The effect of long-term exposure to bisphenol-A (BPA) on estrogen receptor-alpha
      (ER) immunoreactivity was studied in the medial preoptic area, arcuate nucleus
      and the ventromedial nucleus of the hypothalamus of estrous cycling and lactating
      female rats. Pregnant/lactating or estrous cycling rats were exposed to BPA (40
      mg/Kg/day) or peanut oil. Lactating females showed fewer ER-immunoreactive cells
      than non-lactating females in the medial preoptic area and ventromedial nucleus
      of the hypothalamus. BPA induced an increase in ER-immunoreactive cells in the
      medial preoptic nucleus irrespective of lactation. BPA only induced a decrease in
      ER-immunoreactive cells in the arcuate nucleus of the lactating group; oil
      induced an increase in ER-immunoreactive cells in the lactating with respect to
      non-lactating group. The results demonstrate that exposure of adult females to
      BPA modifies the number of ERs.

PMID- 11524156
TI  - Peripheral capsaicin receptors increase in the inflamed rat hindpaw: a possible
      mechanism for peripheral sensitization.
AB  - The vanilloid receptor-1 (VR1) is activated by capsaicin, heat and protons and is
      localized on primary sensory neurons. The present study investigates whether VR1
      increases in the inflamed hindpaw thereby contributing to the peripheral
      sensitization and heat hyperalgesia that characterizes the inflamed state. Forty
      eight hours after intraplantar injection of Complete Freund's Adjuvant into one
      hindpaw, there is a significant increase in the proportion of VR1-labeled
      unmyelinated axons in digital nerves in the inflamed (32.8 +/- 5.9%) compared to
      normal (17.1 +/- 2.6%) hindpaws (t-test, P<0.01). A few, small diameter
      myelinated axons are labeled in normal and inflamed rats with no change in
      percentages following inflammation. The data suggest that an increase in number
      of unmyelinated sensory axons expressing VR1 may be one mechanism underlying
      peripheral sensitization of nociceptors in inflammation.

PMID- 11524157
TI  - Human anterior and frontal midline theta and lower alpha reflect emotionally
      positive state and internalized attention: high-resolution EEG investigation of
      meditation.
AB  - EEG spectral power and coherence estimates in the individually defined delta,
      theta, alpha-1, alpha-2, and alpha-3 bands were used to identify and characterize
      brain regions involved in meditative states, in which focused internalized
      attention gives rise to emotionally positive "blissful" experience. Blissful
      state was accompanied by increased anterior frontal and midline theta
      synchronization as well as enhanced theta long-distant connectivity between
      prefrontal and posterior association cortex with distinct "center of gravity" in
      the left prefrontal region (AF3 site). Subjective scores of emotional experience
      significantly correlated with theta, whereas scores of internalized attention
      with both theta and alpha lower synchronization. Our results propose selective
      associations of theta and alpha oscillating networks activity with states of
      internalized attention and positive emotional experience.

PMID- 11524158
TI  - Presynaptic modulation by group III metabotropic glutamate receptors (mGluRs) of
      the excitatory postsynaptic potential mediated by mGluR1 in rat cerebellar
      Purkinje cells.
AB  - Purkinje neurons were recorded from rat cerebellar slices. Parallel fibres
      stimulation elicited a fast excitatory postsynaptic potential (EPSP) mediated by
      ionotropic glutamate (iGluR) -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid
      (AMPA) receptors followed by the inhibitory gamma-aminobutyric acidA (GABAA)
      dependent postsynaptic potential. In the presence of antagonists for iGluRs and
      for GABAA receptors, brief tetanic activation evoked a slow metabotropic
      glutamate receptor (mGluR)-dependent EPSP (mGluR-EPSP). This mGluR-EPSP was
      blocked by the selective mGluR1 antagonists LY367385 and CPCCOEt, but not by the
      mGluR5 antagonist MPEP. Group II agonists affected neither iGluR-EPSP nor mGluR
      EPSP. Conversely, L-AP4 and L-SOP, group III mGluR agonists, inhibited both iGluR
      and mGluR-EPSPs. The depolarisations evoked by both AMPA and group I agonists
      were unaffected, indicating a presynaptic action of group III mGluRs. These data
      suggest that glutamate released by parallel fibres activates group III mGluR
      autoreceptors, depressing both iGluR- and mGluR1-mediated EPSPs.

PMID- 11524159
TI  - Partial agonistic action of endomorphins in the mouse spinal cord.
AB  - The partial agonistic properties of endogenous mu-opioid peptides endomorphin-1
      and endomorphin-2 for G-protein activation were determined in the mouse spinal
      cord, monitoring the increases in guanosine-5'-o-(3-[35S]thio)triphosphate
      binding. The G-protein activation induced by endogenous opioid peptide beta
      endorphin in the spinal cord was significantly, but partially, attenuated by co
      incubation with endomorphin-1 or endomorphin-2. The data indicates that
      endomorphin-1 and endomorphin-2 are endogenous partial agonists for mu-opioid
      receptor in the mouse spinal cord.

PMID- 11524160
TI  - Chronic loss of ovarian function decreases transport of leptin into mouse brain.
AB  - Loss of ovarian function, such as occurs with menopause in human beings and
      ovariectomy in rodents, results in weight gain. Using multiple-time regression
      analysis, a sensitive technique for quantifying blood-to-brain transport of
      peptides and polypeptides, we found that mice ovariectomized for at least 5 weeks
      had markedly reduced entry of the satiety factor leptin into brain. The rate of
      entry of leptin into brain remained reduced half a year later. The results
      suggest that the weight gain resulting from loss of ovarian function could be
      explained by decreased transport of leptin into the brain.

PMID- 11524161
TI  - Fluorogenic RT-PCR assay (TaqMan) for detection and classification of bovine
      viral diarrhea virus.
AB  - A single tube fluorogenic RT-PCR-based 'TaqMan' assay was developed for detection
      and classification of bovine viral diarrhea virus (BVDV). TaqMan-PCR was
      optimized to quantify BVD virus using the ABI PRISM 7700 sequence detection
      system and dual-labeled fluorogenic probes. Two different gene specific labeled
      fluorogenic probes for the 5' untranslated region (5' UTR) were used to
      differentiate between BVD types I and II. Sensitivity of the single tube TaqMan
      assay was compared with two-tube TaqMan assay and standard RT-PCR using 10-fold
      dilutions of RNA. Single tube TaqMan assay was 10-100-fold more sensitive than
      the two-tube TaqMan assay and the standardized single tube RT-PCR. Specificity of
      the assay was evaluated by testing different BVD virus strains and other bovine
      viruses. A total of 106 BVD positive and negative pooled or single serum samples,
      field isolates and reference strains were tested. Quantitation of cRNA from types
      I and II BVD virus was accomplished by a standard curve plotting cycle threshold
      values (C(T)) versus copy number. Single tube TaqMan-PCR assay was sensitive,
      specific and rapid for detection, quantitation and classification of BVD virus.

PMID- 11524162
TI  - Mycoplasma conjunctivae infection is self-maintained in the Swiss domestic sheep
      population.
AB  - Bacteriological and serological investigations were performed to assess whether
      the domestic sheep population is a reservoir of Mycoplasma conjunctivae in
      Switzerland. Among a sample of 69 sheep showing clinical signs of infectious
      keratoconjunctivitis (IKC) in three Swiss cantons, M. conjunctivae was identified
      53 times (76.8%). A commercially prepared indirect ELISA was used to detect M.
      conjunctivae antibodies in 674 sera of adult sheep. We analysed a stratified
      random sample of 123 sheep herds from 25 out of the 26 Swiss cantons. At least
      one positive animal was detected in 89.4% of the herds. In positive herds
      (n=110), 57.1% of the individual animals tested positive. To assess the
      importance of sheep's age in the spread of M. conjunctivae, 209 sera of adult
      sheep and 93 lamb sera among eight sheep herds were analysed using the indirect
      ELISA. Seroprevalence in 2-6-month-old lambs was 50.5%, indicating that the IKC
      agent is spread in sheep flocks during raising. Lambs experimentally infected
      with M. conjunctivae carried the agent for 8 and 23 weeks, respectively,
      depending on the strain used for challenge. We conclude that the M. conjunctivae
      infection is endemic and self-maintained in the domestic sheep population in
      Switzerland.

PMID- 11524163
TI  - Genetic analysis of virulence factors of Mannheimia (Pasteurella) haemolytica A1.
AB  - Using a molecular genetic approach, the genes that code for the various virulence
      factors of Mannheimia haemolytica A1 have been cloned for detailed
      characterizations. These included analysis of the encoded proteins, their
      biological activities, secretion of the molecules from the bacterium as well as
      their use in a vaccine component. Two newly characterized antigens of M.
      haemolytica A1 have been identified. The first one is a TonB-dependent iron
      regulated outer-membrane receptor that is distinct from the transferrin binding
      proteins. The 84kDa Irp protein exhibits features including a TonB box and a 50
      amino acid region that can adopt occluded beta-barrel structures similar to the
      "plug" domain of the Escherichia coli FhuA and FepA crystal structures.
      Homologues of Irp were identified by analysis of the genome sequences of a number
      of Gram negative mucosal pathogens, including Neisseria meningitidis and N.
      gonorrhoeae. The Neisserial irp genes were cloned by PCR and expressed the 84kDa
      protein as expected, demonstrating that they are functional genes. In addition to
      being regulated by iron and Fur, irp(Mh) undergoes phase variation by a slipped
      strand mispairing mechanism and may represent a contingency locus for iron
      acquisition during an infection. Another locus that codes for a putative adhesin
      molecule has also been partially characterized. This putative adhesin protein is
      highly homologous with the high-molecular-weight adhesin proteins of non-piliated
      non-typable strains of Haemophilus influenzae (NTHi) including Hia, Hsf, HMW1,
      HMW2. Currently, we have cloned the DNA that codes for 2223 amino acids (225kDa)
      and is still missing the stop codon. It is anticipated that when complete, the
      protein could be close to 240kDa, similar to the molecular mass of Hsf. Though
      incomplete, analysis of the adhesin showed that it exhibits characteristics of
      autotransporter (AT) proteins. The role of this high-molecular-weight adhesin in
      infection is being investigated.

PMID- 11524164
TI  - Detection of Brucella melitensis in semen using the polymerase chain reaction
      assay.
AB  - An evaluation of the polymerase chain reaction (PCR) for detection of Brucella
      melitensis DNA in bovine and ovine semen was performed. Since semen contains
      different components that inhibit PCR amplification, a protocol was used to
      purify Brucella-DNA from bovine and ovine semen samples prior to conducting
      amplification of the targeted DNA. When separated fractions of naturally Brucella
      contaminated semen were analyzed by the PCR, most of B. melitensis DNA were
      present in the seminal fluid and non-sperm fractions. The PCR examination results
      for detection of B. melitensis DNA in different semen fractions were compared
      with the results for traditional cultural methods of Brucella from semen. The PCR
      was more sensitive than the traditional cultural methods since it detected
      Brucella-DNA in 12 (10%) out of 120 semen samples while direct culture detected
      only 7 (5.8%) in the same semen samples. The limit of detection by PCR was 100
      CFU/ml of semen. In addition, the results of PCR were available in one day,
      whereas isolation and identification of Brucella organisms required days or even
      weeks. The PCR may be used as a supplementary test for detection of B. melitensis
      in semen.

PMID- 11524165
TI  - Longitudinal study of Salmonella enterica in growing pigs reared in multiple-site
      swine production systems.
AB  - Intensive longitudinal investigations of breeding and growing pig populations in
      two multiple-site swine production systems were conducted in NC, USA. Five
      cohorts of sows and individually identified growing pigs from their litters were
      serially sampled in order to determine the prevalence and serotypes of Salmonella
      enterica in each stage of production based on fecal culture. In addition to fecal
      samples, feed and environmental samples were obtained. Fifteen different
      serotypes were isolated from the two systems, the most frequently isolated
      serotypes were S. typhimurium var Mbandaka and S. typhimurium var Copenhagen. Pig
      prevalence estimates ranged from 0 to 48.1%. Environmental contamination was
      frequently encountered despite cleaning and disinfection. Feed was rarely (2/800,
      0.25%) identified as S. enterica positive. We observed highly variable patterns
      of S. enterica prevalence and serotype profiles within cohorts over time and
      among cohorts within systems. These observations indicate that point estimates of
      S. enterica prevalence and serotypes cannot be considered as reliable indicators
      of the S. enterica status of farms, and that uncontrolled studies of
      interventions to control S. enterica may yield misleading results. These findings
      are critical to the design of epidemiological studies of S. enterica on swine
      farms and may suggest that cohort level, as opposed to farm or company level
      events or management practices, may be important as potential risk factors for S.
      enterica fecal shedding in market age pigs.

PMID- 11524166
TI  - Tetracycline-resistance genes of Clostridium perfringens, Clostridium septicum
      and Clostridium sordellii isolated from cattle affected with malignant edema.
AB  - The minimal inhibitory concentrations (MICs) of 10 antimicrobial agents against a
      total of 33 isolates of Clostridium perfringens, Clostridium septicum and
      Clostridium sordellii from cattle affected with malignant edema in Japan was
      determined. The low MIC activities of benzylpenicillin confirm the place of
      benzylpenicillin as the antibiotics of choice for treatment of malignant edema.
      Five (22%) of 23 C. septicum strains, five (71%) of seven C. perfringens strains
      and all strains of C. sordellii showed resistance to oxytetracycline. These
      oxytetracycline-resistant strains carried tetracycline-resistance genes [tetA(P),
      tetA408(P), tetB(P) and tetM]. The sequences of the tetracycline-resistance genes
      of some C. septicum strains were completely or nearly completely identical to
      those of strains belonging to other clostridiual species. This is the first
      report of resistance of C. septicum to tetracycline.

PMID- 11524167
TI  - Virulence properties of Escherichia coli isolated from ostriches with respiratory
      disease.
AB  - Eight Escherichia coli isolates from ostriches with respiratory disease were
      investigated for the presence of genes encoding the following adhesins: type 1
      pili (fim), pili associated with pyelonephritis (pap), S fimbriae (sfa),
      afimbrial adhesin (afaI), temperature regulated adhesin, curli (crl, csgA) and
      temperature-sensitive hemagglutinin (tsh). Genes for heat labile (LT) and heat
      stable (STa and STb) enterotoxins, Shiga toxins (stx1 and stx2), cytotoxic
      necrotizing factor 1 (cnf), alpha-haemolysin (hly) and aerobactin (aer)
      production were also investigated. Other characteristics investigated were the
      presence of hemagglutination activity, growth on an iron-deficient medium,
      aerobactin production, serum resistance, adherence to chicken tracheal cells,
      pathogenicity for day-old chicks, and serogroup. Serogrouping showed that four
      isolates belonged to serogroup O2, two to serogroup O78, one to serogroup O9, and
      one to serogroup O21. The virulence genes found were: fim in all eight isolates,
      csgA in seven, aer in six, and pap, crl and tsh in one isolate each. All isolates
      analyzed were positive for mannose-resistant hemagglutination, adhered in vitro
      to ciliated tracheal epithelium, grew on iron-deficient medium, and showed serum
      resistance. Pathogenicity tests on day-old chickens revealed one highly
      pathogenic isolate, three of low pathogenicity and four isolates with
      intermediate pathogenicity.

PMID- 11524170
TI  - Proteolysis of insulin-like growth factor binding proteins during preovulatory
      follicular development in cattle.
AB  - The present study was conducted to evaluate changes in follicular fluid (FF)
      insulin-like growth factor binding protein (IGFBP) proteolytic activity and
      levels of steroids and IGFBP during follicular development in cattle. Estrous
      cycles of cows were synchronized with two injections of prostaglandin F2alpha
      (PGF) 11 d apart and follicular growth monitored via daily rectal ultrasonography
      in order to identify the dominant follicle. All cows were ovariectomized 48 hr
      after the second injection of PGF. Follicular fluid was collected individually
      for all follicles > 5 mm and pooled for small (1 to 5 mm) follicles. Follicular
      fluid estradiol and androstenedione levels were greater (P < 0.05) and
      progesterone and IGFBP-3 levels not different (P > 0.10) in large dominant than
      in small (1 to 5 mm) or large (>5 mm) subordinate follicles, whereas IGFBP-2, -4
      and -5 levels were less (P < 0.05) in large dominant than in small or large
      subordinate follicles. To evaluate proteolysis of IGFBPs, FF was incubated with
      recombinant human (125) I-labeled IGFBP-2, -3, -4, and -5 and proteins separated
      by 12% SDS-PAGE. Follicular fluid caused little or no proteolysis of (125)I
      lableled IGFBP-2 or -3. However, cleavage of (125)I-labeled IGFBP-4 and -5 by FF
      from large dominant follicles was greater (P < 0.05) than by FF from small or
      large subordinate follicles indicating that a protease to IGFBP-4 and -5 exists
      in estrogen dominant follicles. We conclude that lower levels of IGFBP-2 in
      estrogen dominant follicles of cattle are not due to increased proteolysis,
      whereas decreases in IGFBP-4 and -5 levels are likely due, in part, to increased
      protease activity. Changes in IGFBP may alter levels of bioavailable IGFs that
      stimulate steroidogenesis and mitogenesis in developing bovine follicles.

PMID- 11524172
TI  - Insulin resistance induced in dairy steers by tumor necrosis factor alpha is
      partially reversed by 2,4-thiazolidinedione.
AB  - The aim of this study was to determine whether 2,4-thiazolidinedione (2,4-TZD)
      influences the effects of peripheral insulin action in steers given recombinant
      bovine tumor necrosis factor (TNF) alpha (rbTNF). Steers were treated once daily
      for 9 d (d0 - d8) with either s.c. injection of rbTNF (2.5 microg/kg), rbTNF +
      i.v. injection of 2,4-TZD (2.0 mg/kg), or s.c. injection of saline (control). The
      plasma glucose, NEFA, and insulin concentrations in the rbTNF-treated group
      increased compared to those in the control and rbTNF + 2,4-TZD groups, whereas
      glucagon concentration decreased. A single i.v. injection of insulin (0.2 U/kg),
      glucose (112.5 mg/kg), or growth hormone (GH)-releasing hormone (GHRH) (0.25
      microg/kg) was performed on d4, d6, and d8, respectively. In the insulin
      challenge, the net area under the glucose curve (AUC) was smaller in the rbTNF
      group than in the control and rbTNF + 2,4-TZD groups. In the glucose challenge,
      the net insulin AUC was smaller in rbTNF + 2,4-TZD group than in rbTNF group. In
      the GHRH challenge, there was no difference in GH responses to GHRH between the
      rbTNF and rbTNF + 2,4-TZD groups, respectively. We conclude that 2,4-TZD
      treatment partially reverses the impairment of peripheral insulin action caused
      by rbTNF injection in steers.

PMID- 11524171
TI  - Ghrelin in domestic animals: distribution in stomach and its possible role.
AB  - Ghrelin, a novel growth-hormone-releasing acylated peptide, was recently isolated
      from rat and human stomachs. In rat, peripheral or central administration of
      ghrelin stimulates the secretion of growth hormone (GH) from the pituitary gland.
      Recent work suggests that ghrelin plays an important role in energy homeostasis,
      body weight, and food intake. We examined the distribution of cells
      immunoreactive to ghrelin in the stomachs of domestic animals and rats, using a
      polyclonal antibody for the N-terminal fragment of rat ghrelin [1-11]. We
      measured the plasma levels of ghrelin before and after feeding in cows, and GH
      levels after central administration of ghrelin in Shiba goats, to elucidate the
      possible role of ghrelin. Immunostained cells were widely distributed from the
      neck to the base of the oxyntic gland in all animals. The plasma ghrelin
      concentration in cows decreased significantly 1 h after feeding, and then
      recovered to pre-feeding levels. Administration of ghrelin into the third
      ventricle in Shiba goats dramatically increased the plasma GH concentration dose
      dependently. These results suggest that ghrelin plays an important role in GH
      secretion and feeding regulation in domestic animals.

PMID- 11524173
TI  - A local increase in the mammary IGF-1: IGFBP-3 ratio mediates the mammogenic
      effects of estrogen and growth hormone.
AB  - A single epithelium-free mammary fat pad was surgically prepared in each of
      twenty-five one-month-old, Friesian heifers. At 18 mo of age, heifers were
      randomly assigned to one of four treatment groups. Treatments were: control (C),
      growth hormone (GH), estrogen (E) or growth hormone + estrogen (GE). Hormones
      were administered for 40 hr before the animals were sacrificed to provide mammary
      samples of parenchyma (PAR), intact fat pad (MFP), and epithelium-free or
      "cleared" fat pad (CFP). IGF-1 and IGF binding protein-3 (IGFBP-3) mRNA was
      highest in CFP and MFP whereas the protein products were highest in PAR. IGFBP-2,
      a 28-kDa IGFBP and a 24-kDa IGFBP were more abundant in CFP and MFP. E and GH
      increased incorporation of [(3)H]thymidine into DNA of PAR. Incorporation of
      [(3)H]thymidine into the DNA of MFP or CFP was minimal. Coincident with the
      changes observed in mammary epithelial proliferation, E increased IGF-1 protein
      in MFP and PAR, and to a lesser extent in CFP. E tended to increase IGF-1 mRNA
      levels in MFP, but not CFP implying that the regulation of IGF-1 expression is
      modulated by adjacent epithelium. GH and E reduced IGFBP-3 protein in PAR and
      increased the 24-kDa IGFBP in CFP and MFP. Increased proliferation of mammary
      parenchymal cells was associated with increased IGF-1 and reduced IGFBP-3 protein
      in mammary tissue. An increase in the ratio of mammary IGF-1: IGFBP-3 likely
      increases the proportion of the mammary IGF-1 available to stimulate
      proliferation. These data also indicate that stromal: epithelial interactions
      regulate the IGF-1 axis in mammary tissue.

PMID- 11524174
TI  - Structure of the genes for porcine endometrial secreted and membrane folate
      binding proteins.
AB  - The endometrium of the pig produces two types of folate binding proteins (FBP)
      which, based on their sequences, are likely to be membrane (m) and secreted (s)
      forms. A clone containing both a gene coding for the sFBP cDNA and a gene coding
      for the mFBP was isolated from a yeast artificial chromosome (YAC) library. Each
      gene was subcloned and sequenced. The gene for sFBP spanned 4.4 kbp and included
      5 exons. The mFBP gene spanned 7.0 kbp and also contained 5 exons. Structures of
      the genes were very similar for the last three exons, and this similarity was
      shared with other known FBP/folate receptor (FR) gene sequences. Unexpectedly,
      portions of introns 3 and 4 of both genes were highly homologous, suggesting the
      possibility that sequences within these introns served some as yet unknown
      function. In contrast, the structures of the 5' exons differed between the two
      genes and other known FBP/FR genes. Comparison of putative promoter regions for
      the two genes with promoter regions for human FBP/FR genes revealed significant
      sequence homology between sFBP and human gammaFBP and between mFBP and human
      alphaFR. These regions of homology may play a role in control of transcription of
      each gene.

PMID- 11524176
TI  - Mutational analysis of ethanol interactions with G-protein-coupled inwardly
      rectifying potassium channels.

PMID- 11524177
TI  - Ethanol-induced conditioned taste aversion in the rat: effects of 5,7
      dihydroxytryptamine lesion of the dorsal raphe nucleus.

PMID- 11524178
TI  - Further investigation of citalopram on alcohol consumption in heavy drinkers:
      responsiveness possibly linked to the DRD2 A2/A2 genotype.

PMID- 11524179
TI  - Ethanol preference in Maudsley and RXNRA recombinant inbred strains of rats.

PMID- 11524180
TI  - Chronic ethanol intoxication enhances the production of cytokine-induced
      neutrophil chemoattractant and macrophage inflammatory protein-2 by hepatocytes
      after human immunodeficiency virus-1 glycoprotein 120 vaccination.
AB  - Chemokines are implicated in the pathogenesis of alcoholic liver disease and
      human immunodeficiency virus-1 (HIV-1) infection. Thus, this work examined the
      regulation of chemokines --i.e., cytokine-induced neutrophil chemoattractant
      (CINC) and macrophage inflammatory protein-2 (MIP-2)--produced by hepatocytes
      after HIV-1 glycoprotein 120 (gp120) vaccination in Wistar rats fed with ethanol
      for 30 weeks. HIV-1 gp120 in complete Freund's adjuvant was given by
      intrainguinal route at a dose of 5 g/kg, followed by two booster shots in
      incomplete Freund's adjuvant at a weekly interval. Samples were taken 1 week
      after the last injection was given. Results show that anti-HIV-1 gp120 antibody
      titer was suppressed by 40% in the ethanol-fed rats, compared with findings in
      the parallel controls. However, serum CINC and MIP-2 levels were more elevated in
      the ethanol-fed rats than in the pair-fed group. The likely sources of these
      chemokines are the hepatocytes. After HIV-1 gp120 treatment, isolated hepatocytes
      obtained from the ethanol-fed group produced more CINC and MIP-2 than did those
      of pair-fed rats. Concomitantly, mRNA expression for these two chemokines and
      hepatic sequestration of neutrophils were upregulated. Ethanol feeding alone
      suppressed chemokine release, but it did not alter mRNA expression in isolated
      hepatocytes. Administration of Freund's adjuvant (without HIV-1 gp120) did not
      induce chemokine release in vivo and did not prime isolated hepatocytes for
      enhanced chemokine production in vitro. These results show that chronic ethanol
      intoxication affects the ability of the host to respond to HIV-1 gp120
      vaccination.

PMID- 11524181
TI  - Effects of nicotine on ethanol dependence and brain damage.
AB  - Almost all alcoholics (80%-95%) smoke tobacco. When alcoholics binge, they
      achieve high, sustained blood alcohol levels, become physically dependent, and
      often suffer loss of cognition and other higher cortical functions. Nicotine
      could have a modulatory effect on ethanol drinking behavior and ethanol-induced
      brain damage through its cholinergic actions. To determine whether nicotine
      altered alcohol dependence, alcohol-induced brain damage, or both, a rat model of
      binge drinking was used to study the effects of nicotine on the alcohol
      withdrawal syndrome and its associated brain damage. After administration of the
      last dose of ethanol in a 4-day binge model, rats remained intoxicated for
      approximately 5 h, slowly returned to a neutral state, and entered a hyperexcited
      period, which peaked around 24 h and lasted a total of 60 h. Behavioral signs of
      withdrawal included splayed limbs, tremors, and seizures. Continuous transdermal
      nicotine did not alter the duration or severity of ethanol withdrawal. The 4-day
      binge ethanol treatment caused considerable brain damage in the perirhinal
      cortex, entorhinal cortex, ventral dentate gyrus, and olfactory bulb as
      visualized with amino cupric silver stain. Nicotine alone caused little or no
      brain damage and did not markedly alter binge ethanol-induced damage in cortical
      or hippocampal regions. In the olfactory bulb, nicotine reduced ethanol-induced
      brain damage. Although results of other studies seem to indicate that nicotine
      increases alcohol consumption, our findings indicate that nicotine does not
      markedly change the development of alcohol dependence or alcohol-induced cortical
      damage.

PMID- 11524182
TI  - Visual axis opacification after pediatric intraocular lens implantation.

PMID- 11524183
TI  - Therapeutic lamellar keratoplasty with an automated microkeratome.
AB  - Penetrating keratoplasty (PKP) is the predominant form of corneal transplantation
      because both manual and automated lamellar keratoplasty are technically difficult
      and lead to complications such as irregularities and scarring. A microkeratome
      for laser in situ keratomileusis can be used to overcome these disadvantages. We
      describe a technique of lamellar keratoplasty performed with an automated
      microkeratome to treat corneal opacities in the anterior third of the cornea.
      This easy, accurate technique leads to good visual results and represents a good
      alternative to PKP in treating anterior corneal opacities.

PMID- 11524184
TI  - Pigment vacuum iridectomy for phakic refractive lens implantation.
AB  - I present a technique designed to ensure an atraumatic patent basal iridectomy
      for phakic refractive lens implantation. The technique divides the iridectomy
      procedure into 2 steps. First, the stromal layer is removed by surgical excision.
      Then, the pigment layer is removed by gentle vacuum aspiration with a 25 gauge
      cannula. Atraumatic, small, basal peripheral iridectomies that are functional and
      cosmetically pleasing have been performed in 12 eyes. There were no cases of
      large amounts of pigment debris deposited in the trabecular meshwork as checked
      by gonioscopy. Pigment vacuum iridectomy may be a reliable procedure to ensure a
      proper basal iridectomy in any type of anterior segment eye surgery.

PMID- 11524185
TI  - Bimanual Sinskey hook technique to enlarge a preexisting capsulorhexis.
AB  - We describe a technique of enlarging a small primary capsulorhexis. Two Sinskey
      hooks are introduced through the side ports. One hook is placed above the
      anterior capsulorhexis margin with its tip pointing down, and the other is placed
      beneath the anterior capsulorhexis margin with its tip pointing up. A small nick
      is made between the tips of the 2 hooks, and the capsulorhexis is extended with a
      Utrata capsulorhexis forceps. This technique does not require additional
      instrumentation, impart zonular stress, or disturb wound architecture or
      integrity.

PMID- 11524186
TI  - Temporary graft for closed-system cataract surgery during corneal triple
      procedures.
AB  - Performing phacoemulsification during a triple corneal procedure has many
      advantages. Operating in a closed chamber makes surgery easier and safer. In some
      cases, however, a dense corneal opacity may prevent closed-chamber surgery,
      necessitating the use of an open-sky technique. In these cases, a temporary
      corneal graft using a corneal button not suitable for penetrating keratoplasty is
      proposed to allow phacoemulsification and foldable intraocular lens implantation
      through a corneal tunnel. The temporary corneal graft is replaced with a
      permanent graft after these steps are completed. This technique was effective in
      3 patients with cataract and dense corneal opacity.

PMID- 11524187
TI  - 1998 European Cataract Outcome Study: report from the European Cataract Outcome
      Study Group.
AB  - PURPOSE: To collect clinical data on cataract surgery to allow participating
      surgeons to compare their performance with that of their colleagues in an
      anonymous manner. SETTING: Surgeons from 31 surgical units providing cataract
      surgery in 13 European countries. METHODS: Every patient at each participating
      unit having surgery during 1 study month was evaluated. Data were reported to the
      coordinating center at the time of surgery and at the final examination. When the
      study was closed 6 months after surgery, all participants were provided with the
      outcomes from their own patients so they could compare them with outcomes from
      other centers. RESULTS: The study included preoperative and intraoperative data
      on 2950 patients. Complete follow-up data were available for 2731 patients. The
      surgical audit included surgically induced astigmatism, proximity of target
      refraction, and the frequency of major complications. For each variable, a large
      variation in outcome between participating centers was found. Most centers had
      results both above and below average for different variables. CONCLUSION:
      Cataract surgery data collected from 31 units in 13 European countries allowed
      participants to compare their performance with that of their colleagues in an
      anonymous manner. Significant variation was found in the outcomes among the
      units, with many units reporting results above and below the averages.

PMID- 11524188
TI  - Necessity of vitrectomy when optic capture is performed in children older than 5
      years.
AB  - PURPOSE: To determine whether anterior vitrectomy is necessary when optic capture
      is performed in children between 5 and 12 years old with congenital cataract.
      SETTING: Iladevi Cataract and IOL Research Center, Ahmedabad, India. METHODS:
      This prospective randomized controlled study comprised 41 eyes of 25 children
      whose mean age was 83.57 months (range 60 to 144 months). Intraocular lens (IOL)
      implantation with optic capture through a primary posterior continuous
      curvilinear capsulorhexis was performed in all the eyes. The IOL haptics were bag
      fixated. Patients were randomly assigned to 1 of 2 groups. Vitrectomy was
      performed in 1 group (n = 21 eyes) and not performed in the other group (n = 20
      eyes). The mean follow-up was 21.04 months. A Student t test and chi-square test
      were used for statistical analysis. RESULTS: All eyes in the vitrectomy group and
      30% in the no-vitrectomy group had a clear visual axis at the last follow-up (P
      <.001) The visual axis was obscured as a result of anterior vitreous fibrosis in
      70% of eyes in the no-vitrectomy group. High-contrast visual acuity was not
      significantly different between groups (P =.28). Low-contrast sensitivity was
      significantly better in the vitrectomy group (P =.02). Eighteen eyes (85.7%) in
      the vitrectomy group and 16 eyes (80%) in the no-vitrectomy group developed
      deposits on the IOL (P =.62). The deposits were present at the last follow-up in
      4 eyes (19.0%) in the vitrectomy group and in 6 eyes (30.0%) in the no-vitrectomy
      group (P =.85). Three eyes (14.3%) in the vitrectomy group and 8 eyes (40.0%) in
      the no-vitrectomy group developed synechias (P =.06). CONCLUSION: The results
      suggest that anterior vitrectomy is necessary with optic capture in children with
      congenital cataract who are between 5 and 12 years old.

PMID- 11524189
TI  - Effect of optic size on posterior capsule opacification: 5.5 mm versus 6.0 mm
      AcrySof intraocular lenses.
AB  - PURPOSE: To determine the effect of intraocular lens (IOL) optic diameter on
      posterior capsule opacification (PCO) using digital retroillumination images.
      SETTING: Eye Department, St. Thomas' Hospital, London, United Kingdom. METHODS:
      In this prospective study, 60 patients with senile cataract had routine
      phacoemulsification by a single surgeon and received standardized medication. The
      patients were divided into 2 equal groups. The first group received a 5.5 mm 3
      piece AcrySof IOL (MA30BM, Alcon) inserted in the bag. The second group received
      a 6.0 mm 3-piece AcrySof IOL (MA60BM, Alcon). Retroillumination images were
      obtained 1, 30, 90, 180, and 360 days postoperatively. The percentage area of PCO
      was calculated objectively by dedicated software at 90, 180, and 360 days. At 1
      day, the degree of capsulorhexis-IOL contact was determined by inspecting the
      images. RESULTS: Throughout the follow-up, there was less PCO in the 6.0 mm optic
      group than in the 5.5 mm optic group, and the difference reached significance 1
      year postoperatively (P =.0017). At 1 year, the median percentage of PCO was 1.5%
      (95% confidence interval [CI] 1.4-5.3) in the 6.0 mm group and 6.9% (95% CI 5.8
      18.0) in the 5.5 mm group. CONCLUSIONS: A larger IOL optic diameter was
      associated with less PCO.

PMID- 11524190
TI  - Determinants of visual outcome after pars plana vitrectomy for posteriorly
      dislocated lens fragments in phacoemulsification.
AB  - PURPOSE: To evaluate the visual outcome of patients with posteriorly dislocated
      lens fragments after phacoemulsification managed with pars plana vitrectomy (PPV)
      and identify risk factors for poor visual outcome. SETTING: Vitreo-Retinal
      Service, St. Paul Eye Unit, Liverpool, United Kingdom. METHODS: The medical
      records of all patients who had PPV for posteriorly dislocated lens fragments
      after phacoemulsification between March 1993 and August 1998 were retrospectively
      reviewed. Demographics, preexisting eye conditions, details of the previous
      cataract surgery, findings at presentation, details of the vitreoretinal
      procedure, final visual acuity, and complications observed during the follow-up
      were evaluated. Univariate and multiple regression analyses were used to
      determine the significance of these clinical variables as determinants of poor
      visual outcome (visual acuity 6/12 or worse). RESULTS: Of the 106 patients
      identified, 89 had a full set of data and were included in the study. In 79
      patients (89%), PPV was performed from 1 to 357 days (median 15 days) after
      cataract extraction. In 10 patients (11%), PPV was done on the same day as the
      cataract surgery. Sixty-two patients (69%) had a final visual acuity of 6/12 or
      better. Preexisting eye disease (P <.01), PPV delayed for more than 4 weeks (P
      <.03), occurrence of retinal detachment after vitrectomy (P <.01), and the use of
      ultrasound (US) fragmentation (P <.01) were statistically significantly
      correlated with a poor visual outcome. CONCLUSIONS: Posterior dislocated lens
      fragments after phacoemulsification were safely retrieved using PPV. It appears
      that intervening early (within 4 weeks) and avoiding the use of US fragmentation
      are associated with a better visual outcome and reduced rate of postoperative
      complications.

PMID- 11524191
TI  - Cataract surgery under topical anesthesia in patients with coexisting glaucoma.
AB  - PURPOSE: To evaluate and compare levels of patient discomfort and complications
      during phacoemulsification with implantation of a foldable intraocular lens (IOL)
      under topical lidocaine hydrochloride in patients with and without various forms
      of chronic open-angle and chronic angle-closure glaucoma. SETTING: Two university
      eye centers in Germany. METHODS: This prospective nonrandomized comparative study
      comprised 176 eyes of 176 patients with various forms of chronic open-angle
      glaucoma and chronic angle-closure glaucoma. Eyes with cataract and without a
      glaucoma diagnosis or history of intraocular surgery served as a control group (n
      = 212). All patients received a minimum of 5 doses (2 drops per dose) of topical
      lidocaine hydrochloride 2% before standard temporal clear corneal
      phacoemulsification and foldable IOL implantation. No intracameral anesthetic
      injection was given, and no systemic sedatives were used. The main outcome
      measures were the number of complications and adverse events. RESULTS: The
      intraoperative complication rate in all patients (n = 388) was capsule tear,
      1.3%; zonule tear, 1.8%; vitreous loss, 1.0%; iris prolapse, 0.8%. No
      statistically significant differences in intraoperative or early postoperative
      complications were found between the glaucoma and control groups. The mean pain
      scores of patients were 0.38 +/- 1.1 (SD) in the glaucoma group and 0.36 +/- 0.8
      in the control group (P =.21) Patient preference for cataract surgery under
      topical anesthesia was similar in both groups. CONCLUSIONS: Surgery-related
      complications and patient discomfort were similar in patients with and without
      glaucoma who had phacoemulsification and IOL implantation under topical
      anesthesia. These results indicate that topical anesthesia is safe for routine
      phacoemulsification with foldable IOL implantation in patients with glaucoma and
      does not compromise patient comfort.

PMID- 11524192
TI  - Topical plus intracameral lidocaine versus retrobulbar anesthesia in
      phacotrabeculectomy: prospective randomized study.
AB  - PURPOSE: To compare the efficacy and safety of topical and retrobulbar anesthesia
      for phacotrabeculectomy. SETTING: Hospital Ramon y Cajal, Madrid, Spain. METHODS:
      This prospective study comprised 60 patients (60 eyes) having phacotrabeculectomy
      surgery. Patients were randomly assigned to 1 of 2 groups receiving topical
      anesthesia plus intracameral lidocaine 1% or retrobulbar anesthesia. Patients
      were asked to document the discomfort they experienced during the administration
      of the anesthetic agent, during surgery, and postoperatively using a numeric pain
      scale. Complications and surgical conditions were also evaluated. RESULTS: The
      retrobulbar group reported significantly more discomfort during administration of
      the anesthetic agent than the topical group (P < .001). The topical group
      reported significantly more discomfort intraoperatively (P < .01). Eyelid
      squeezing and eyeball movement were more common in the topical group; however,
      neither was a problem to the surgeon. There was no difference in surgical
      conditions (P = .38) or the postoperative pain scores between the 2 groups (P =
      .06). One patient receiving topical anesthesia developed a suprachoroidal
      hemorrhage intraoperatively. CONCLUSIONS: Topical anesthesia supplemented with
      intracameral lidocaine was an effective alternative to retrobulbar anesthesia for
      phacotrabeculectomy. Although the degree of patient discomfort was significantly
      higher during surgery under topical anesthesia, the method avoids the pain and
      complications associated with a retrobulbar injection.

PMID- 11524193
TI  - Effect of sub-Tenon's and peribulbar anesthesia on intraocular pressure and
      ocular pulse amplitude.
AB  - PURPOSE: To compare the effect of peribulbar and sub-Tenon's anesthesia on
      intraocular pressure (IOP) and ocular pulse amplitude (OPA) in the injected eye
      and the fellow noninjected (control) eye. SETTING: Tel Aviv Medical Center, Tel
      Aviv, Israel. METHODS: This prospective study measured IOP and OPA at baseline
      and 1 and 10 minutes after administration of lidocaine anesthesia in 40
      consecutive adult patients having elective cataract surgery. RESULTS: The IOP
      remained stable throughout the study with both modes of anesthesia. One minute
      after injection of the anesthetic agent, the OPA was significantly decreased in
      the injected eyes in both the sub-Tenon's (24%; P < .05) and peribulbar (25%; P <
      .05) groups. The decrease in the OPA in the sub-Tenon's group (14%; P < .05) was
      detectable after 10 minutes in the control eyes. In the peribulbar anesthesia
      group, the OPA in the control eyes increased significantly (9%; P < .05) 1 minute
      after injection of the anesthetic agent, returning to preinjection levels 10
      minutes after the injection. CONCLUSIONS: The OPA in the eyes in which lidocaine
      was injected decreased significantly in both the sub-Tenon's and peribulbar
      groups. These findings have implications for the management of patients whose
      ocular circulation may be compromised.

PMID- 11524194
TI  - Effect of topical brimonidine on intraocular pressure after small incision
      cataract surgery.
AB  - PURPOSE: To evaluate the effect of brimonidine 0.2% on intraocular pressure (IOP)
      after small incision cataract surgery. SETTING: Department of Ophthalmology,
      University of Vienna, Vienna, Austria. METHODS: This prospective randomized study
      comprised 80 eyes of 40 patients scheduled for small incision cataract surgery in
      both eyes. In each patient, 1 eye was randomly assigned to receive 1 drop of
      brimonidine 0.2% or no treatment (control) immediately after surgery. The fellow
      eye received the other assigned treatment. All patients had standardized surgery
      by the same surgeon with sodium hyaluronate 1%, a temporal 3.5 mm sutureless
      posterior limbal incision, phacoemulsification, and implantation of a foldable
      intraocular lens. The IOP was measured preoperatively as well as 6 and 20 to 24
      hours and 1 week postoperatively. RESULTS: Six hours after surgery, the mean
      increase in IOP was 4.7 mm Hg +/- 6.1 (SD) in the brimonidine group and 4.6 +/-
      5.3 mm Hg in the control group. In each group, 17 eyes (43%) had an IOP increase
      of 5 mm Hg or more. Twenty to 24 hours after surgery, the mean increase in IOP
      was 1.5 +/- 4.2 mm Hg in the brimonidine group and 1.6 +/- 4.4 mm Hg in the
      control group. There were no statistically significant between-group differences
      at any measurement. CONCLUSIONS: In both groups, IOP significantly increased 6
      hours and 20 to 24 hours after small incision cataract surgery. Brimonidine 0.2%
      failed to reduce the IOP increase observed after small incision cataract surgery.

PMID- 11524195
TI  - Comparison of ketorolac tromethamine 0.5% and rimexolone 1% to control
      inflammation after cataract extraction. Prospective randomized double-masked
      study.
AB  - PURPOSE: To compare the efficacy of a topical nonsteroidal anti-inflammatory
      agent (ketorolac tromethamine 0.5%) with that of a topical steroid (rimexolone
      1%) to control inflammation after cataract surgery. SETTING: Storm Eye Institute,
      Department of Ophthalmology, Medical University of South Carolina, Charleston,
      South Carolina, USA. METHODS: Thirty-six patients were prospectively and randomly
      assigned to receive topical treatment with either ketorolac tromethamine 0.5% or
      rimexolone 1% starting the day after routine cataract extraction. Treatment was
      masked to both patient and investigator. Each patient had uneventful small
      incision phacoemulsification with placement of a foldable posterior chamber
      intraocular lens. Patients used 1 of the 2 antiinflammatory agents 4 times each
      day starting 24 hours after surgery. No antiinflammatory medications were used
      preoperatively, intraoperatively, or for 24 hours postoperatively. Signs and
      symptoms of inflammation, intraocular pressure (IOP), and Kowa cell and flare
      measurements were evaluated 1, 4, 7, and 30 days postoperatively. RESULTS: There
      was no statistically significant difference in any measurement of postoperative
      inflammation between the 2 groups. There was no difference in objective or
      subjective cell and flare measurements. In addition, there was no difference in
      IOP measurements between groups. CONCLUSIONS: Ketorolac tromethamine 0.5% was as
      effective as rimexolone 1% in reducing inflammation after cataract surgery. These
      results suggest that ketorolac tromethamine 0.5% is a safe and effective
      antiinflammatory alternative to steroids after cataract extraction.

PMID- 11524196
TI  - Traumatic wound dehiscence after cataract extraction.
AB  - PURPOSE: To study the visual outcome and factors associated with it in patients
      with traumatic dehiscence of a cataract surgery wound. SETTING: Department of
      Ophthalmology and the Brown School of Public Health and Community Medicine, The
      Hebrew University-Hadassah Medical School, Jerusalem, Israel. METHODS: A
      retrospective observational study of 37 eyes of 37 consecutive patients with
      traumatic wound dehiscence of a cataract surgery wound was conducted. A complete
      ophthalmic evaluation was performed in all patients. Statistical analysis was
      done to identify factors associated with the best corrected visual acuity at the
      end of follow-up. RESULTS: Patients had extracapsular cataract extraction (n =
      29), intracapsular cataract extraction (n = 4), or lensectomy (n = 4). No patient
      had phacoemulsification via a small incision. A univariate analysis showed that
      factors associated with a worse visual outcome included the presence at
      presentation of hyphema (P = .05), intraocular lens dislocation or loss (P =
      .006), vitreous hemorrhage (P = .0002), scleral rupture (P = .001), a long
      interval from surgery to trauma (P < .0001), and fall as the cause of trauma (P <
      .0001). In a multivariate model, only a surgery-to-trauma interval longer than 8
      weeks was associated with a worse visual outcome (P < .0001). Visual acuity
      immediately after trauma was a poor predictor of final visual acuity.
      CONCLUSIONS: Visual outcome after traumatic wound dehiscence of a cataract
      surgery wound was strongly associated with the interval from surgery to trauma.
      Other factors were less reliable predictors of visual outcome. Traumatic wound
      dehiscence only moderately affected visual outcome after cataract surgery in most
      cases.

PMID- 11524197
TI  - Phacoemulsification combined with silicone oil removal through a posterior
      capsulorhexis.
AB  - PURPOSE: To evaluate the technique of silicone oil removal through a posterior
      capsulorhexis combined with phacoemulsification and intraocular lens (IOL)
      implantation. SETTING: Dr. Rajendra Prasad Center for Ophthalmic Sciences, New
      Delhi, India. METHODS: Fifteen eyes of 15 patients had phacoemulsification with
      removal of silicone oil, which had been used for intraocular tamponade after a
      previous pars plana vitrectomy. Eyes with a stable retina were included in the
      series. In all eyes, the silicone oil was removed through a planned posterior
      capsulorhexis after phacoemulsification. The parameters evaluated were the
      primary diagnosis, duration between silicone oil instillation and
      phacoemulsification, type of cataract, preoperative and postoperative best
      corrected visual acuities (BCVAs), and complications such as frequency of retinal
      redetachment and secondary cataract. RESULTS: Vitreoretinal surgery with silicone
      oil instillation was performed for rhegmatogenous-tractional detachment resulting
      from Eales' disease in 6 eyes and from proliferative diabetic retinopathy in 2
      eyes, for primary rhegmatogenous retinal detachment in 6 eyes, and for traumatic
      rhegmatogenous detachment in 1 eye. The mean duration between the silicone oil
      instillation and phacoemulsification was 7.5 months +/- 3.8 (SD). Fourteen eyes
      had posterior subcapsular cataract, and 10 had nuclear sclerosis. Preoperative
      BCVA was worse than 6/60 in all eyes. The BCVA was 6/60 or better in 9 eyes after
      a minimum follow-up of 6 months. Two eyes had choroidal detachment in the early
      postoperative period. No eye had vitreous hemorrhage, retinal redetachment,
      secondary cataract, clinically significant endothelial decompensation or macular
      edema, or a dislocated IOL. CONCLUSION: The results indicate that silicone oil
      removal through a posterior capsulorhexis during phacoemulsification is a viable
      option and can be performed in selected cases of cataract with previous silicone
      oil instillation and a stable retina.

PMID- 11524198
TI  - Anterior chamber intraocular lens for high myopia: five year results.
AB  - PURPOSE: To evaluate the effectiveness of the surgical correction of high myopia
      5 years after anterior chamber intraocular lens (IOL) implantation and to analyze
      the lens position and related complications. SETTING: Federal University of Sao
      Paulo-Escola Paulista de Medicina, Sao Paulo, Brazil. METHODS: This prospective
      study comprised 26 eyes that were implanted with an anterior chamber IOL (model
      ZB5M) and had a minimum follow-up of 5 years. Before and after surgery, manifest
      and cycloplegic refractions were done; slitlamp examination was performed;
      anterior chamber depth was measured; and keratometry, ophthalmoscopy, and central
      corneal endothelial cell count were performed. At the last follow-up,
      computerized biomicroscopy of the anterior segment was also done. RESULTS: The
      spherical equivalent decreased from -16.5 diopters (D) +/- 4.1 (SD)
      preoperatively to -0.9 +/- 0.9 D postoperatively. At the last examination, 57.7%
      of eyes had a spherical equivalent refraction within +/-1.0 D of emmetropia. Of
      eyes with a preoperative best spectacle-corrected visual acuity of 20/40 or
      better, 73.3% had an uncorrected visual acuity of 20/40 or better
      postoperatively. The mean tilt caused by the IOL was 4.4 +/- 2.7 degrees (range
      0.5 to 12.2 degrees) and the mean IOL decentration, 0.3 +/- 0.2 mm (range 0.02 to
      0.8 mm). The mean decrease in the endothelial cell count was 1.5%, with a mean
      cell density of 2808 +/- 305 cells/mm2 preoperatively and 2765 +/- 242 cells/mm2
      postoperatively. Pupillary ovalization was observed in 12 eyes (46.1%).
      CONCLUSIONS: The anterior chamber IOL safely and effectively corrected high
      myopia.

PMID- 11524199
TI  - Changes in measured intraocular pressure after hyperopic photorefractive
      keratectomy.
AB  - PURPOSE: To investigate the effect of hyperopic photorefractive keratectomy (PRK)
      on intraocular pressure (IOP) measurements. SETTING: University of Ottawa Eye
      Institute, Ottawa Hospital, Ottawa, Canada. METHODS: In this retrospective cohort
      study, IOP and central corneal thickness (CCT) were measured preoperatively and
      at 1, 2, 3, 6, 12, 18, and 24 months in 191 eyes that had hyperopic PRK with the
      VISX Star excimer laser. All corrections applied were between +1.00 and +6.50
      diopters (D) of sphere and less than 3.75 D of cylinder. RESULTS: At all
      postoperative examinations, the mean IOP in the hyperopic PRK group was 1.0 to
      1.8 mm Hg lower than the preoperative IOP (P <.001). A large range of IOP changes
      was found across the population; eg, at 6 months, 49% of the eyes had a change in
      IOP from baseline of at least +/-3 mm Hg. A mean reduction of 19 microm of CCT
      was found with pachymetry after surgery (P < .001). The change in IOP readings
      postoperatively was not correlated with age, sex, keratometric readings, or
      applied correction. Changes in IOP were strongly correlated with preoperative IOP
      at all time points and with preoperative CCT at 18 and 24 months (P < .001).
      After hyperopic PRK, the measured IOP was more likely to increase in patients
      with preoperative IOPs less than 14.5 mm Hg and more likely to decrease in
      patients with preoperative IOPs above 14.5 mm Hg. CONCLUSION: Changes in IOP
      after hyperopic PRK were similar to changes after myopic PRK, despite only
      minimal changes in the CCT. This suggests that hyperopic PRK results in
      biomechanical effects that modify the elastic properties of the cornea beyond the
      changes in rigidity expected from central corneal thinning. There was a strong
      negative correlation between the measured preoperative IOP and the change in IOP
      postoperatively that was likely the result of regression of the mean effect.

PMID- 11524200
TI  - 200 Hz flying-spot technology of the LaserSight LSX excimer laser in the
      treatment of myopic astigmatism: six and 12 month outcomes of laser in situ
      keratomileusis and photorefractive keratectomy.
AB  - PURPOSE: To evaluate safety, efficacy, predictability, and stability in the
      treatment of myopic astigmatism with laser in situ keratomileusis (LASIK) and
      photorefractive keratectomy (PRK) using the 200 Hz flying-spot technology of the
      LaserSight LSX excimer laser. SETTING: SynsLaser Clinic, Tromso, Norway. METHODS:
      This retrospective study included 110 eyes treated with LASIK and 87 eyes treated
      with PRK that were available for evaluation at 6 and 12 months, respectively. The
      mean preoperative spherical equivalent (SE) was -5.35 diopters (D) +/- 2.50 (SD)
      (range -1.13 to -11.88 D) in the LASIK eyes and -4.72 +/- 2.82 D (range -1.00 to 
      15.50 D) in the PRK eyes. The treated cylinder was 4.00 D in both groups. Eleven
      (8.5%) LASIK eyes and 8 (7.4%) PRK eyes had secondary surgical procedures before
      6 and 12 months, respectively, and were excluded when the 6 and 12 month outcomes
      were analyzed. RESULTS: None of the eyes lost 2 or more lines of best spectacle
      corrected visual acuity. Seventy-seven percent of the LASIK eyes and 78% of the
      PRK eyes achieved an uncorrected visual acuity of 20/20 or better; 98% in both
      groups achieved 20/40 or better. The SE was within +/-0.5 D of the desired
      refraction in 83% of the LASIK eyes and 77% of the PRK eyes; it was within +/-1.0
      D in 97% and 98%, respectively. The cylinder correction had a mean magnitude of
      error of 0.04 +/- 0.31 D (range -0.96 to +0.85 D) in the LASIK eyes and 0.02 +/-
      0.37 D (range -1.44 to +0.72 D) in the PRK eyes. Refractive stability was
      achieved at 1 month and beyond in the LASIK eyes and at 3 months and beyond in
      the PRK eyes. CONCLUSION: The outcomes of this study are comparable to those
      achieved with lasers that use small-beam technology with a lower frequency, as
      well as with other types of delivery systems. They suggest that the 200 Hz
      technology used in the LaserSight LSX excimer laser is safe, effective, and
      predictable and that with LASIK and PRK the results are stable when treating low
      to moderate myopia and astigmatism up to 4.0 D.

PMID- 11524201
TI  - Myopic and hyperopic laser in situ keratomileusis retreatments: indications,
      techniques, limitations, and results.
AB  - PURPOSE: To assess the efficacy of myopic and hyperopic laser in situ
      keratomileusis (LASIK) retreatment procedures. SETTING: Mater Private Hospital,
      Dublin, Ireland. METHODS: Retreatment was defined as either lifting the
      previously created flap or when this was not possible, cutting a new flap. Fifty
      six patients were retreated, 17 with hyperopia (Group 1) and 39 with myopia
      (Group 2). The mean preoperative spherical equivalent in Group 1 was +3.79
      diopters (D) +/- 1.53 (SD) (range +1.75 to +8.12 D) and in Group 2, -5.46 +/-
      2.87 D (range -0.38 to -15.25 D). RESULTS: The indications for retreatment were
      undercorrection, decentration, epithelial ingrowth, and central island.
      Postoperatively, the mean spherical equivalents in Groups 1 and 2 were +1.11 +/-
      2.02 D (range -1.75 to +5.50 D) and -1.02 +/- 2.20 D (range +4.75 to -9.00 D),
      respectively. In Group 1, the uncorrected visual acuity (UCVA) was 6/12 or better
      in 5.8% preoperatively and in 35% postoperatively. In Group 2, the UCVA was 6/12
      or better in 5.1% preoperatively and in 59.0% postoperatively. Although 29% of
      the hyperopic eyes and 8% of the myopic eyes lost 1 Snellen line of best
      corrected visual acuity (BCVA), there was an improvement (of 1 or more lines) in
      BCVA in 12% and 49%, respectively. In cases that were decentered preoperatively,
      the postoperative optical zone ablation centration was better in 85.7% of Group 1
      eyes and 61.5% of Group 2 eyes. Corneal complications following retreatment
      included peripheral scarring, epithelial ingrowth, Bowman's folds, and
      keratectasia. CONCLUSIONS: Both myopic and hyperopic retreatments resulted in a
      stable refractive outcome. Myopic retreatments were superior to hyperopic
      retreatments in both efficacy and safety.

PMID- 11524202
TI  - Valacyclovir inhibition of recovery of ocular herpes simplex virus type 1 after
      experimental reactivation by laser in situ keratomileusis.
AB  - PURPOSE: To determine whether the systemic administration of valacyclovir
      (Valtrex) reduces ocular shedding of herpes simplex virus type 1 (HSV-1) after
      laser in situ keratomileusis (LASIK) in the New Zealand White (NZW) rabbit
      latency model. SETTING: Department of Ophthalmology, University of Pittsburgh
      School of Medicine, Pittsburgh, Pennsylvania, USA. METHODS: New Zealand White
      rabbits latently infected with HSV-1 W strain were divided into 3 groups. The
      first received 100 mg/kg/day of valacyclovir; the second, 200 mg/kg/day of
      valacyclovir; and the third (control), saline. One half the total dose of
      valacyclovir was delivered via intraperitoneal injections twice daily for 7 days
      beginning with 1 dose before LASIK. The HSV-1 ocular shedding was determined from
      eye cultures for 7 days after LASIK. RESULTS: The administration of both 100
      mg/kg/day and 200 mg/kg/day of valacyclovir significantly reduced the number of
      eyes (1/16 in both groups) and the total number of HSV-1 shedding days (1/122 and
      2/122, respectively) from which HSV-1 was recovered compared to the control group
      (7/16 [P =.0396] and 14/129 [P <.007], respectively). CONCLUSIONS: Systemic
      administration of valacyclovir significantly reduced HSV-1 ocular shedding after
      LASIK in the NZW rabbit latency model. The clinical implications of this study
      suggest that patients with a history of recurrent ocular herpes may be able to
      safely have LASIK with less risk of a recurrent herpetic episode while on
      valacyclovir antiviral prophylaxis.

PMID- 11524203
TI  - Dilation of Schlemm's canal in viscocanalostomy: comparison of 2 viscoelastic
      substances.
AB  - PURPOSE: To study the injection of viscoelastic material into Schlemm's canal
      adjacent to and 6.0 mm from the scleral flap during viscocanalostomy in an
      autopsy eye model. SETTING: Department of Ophthalmology, Storm Eye Institute,
      Medical University of South Carolina, Charleston, South Carolina, USA. METHODS:
      Viscocanalostomy was performed in 8 postmortem human globes. Sodium hyaluronate
      (Healon GV or Healon5) was injected into 1 side of Schlemm's canal, with the
      other side serving as a control in some eyes. The eyes were prepared for light
      microscopic analysis, and serial pathologic sections were taken adjacent to the
      flap and 6.0 mm circumferentially from the flap. The area of Schlemm's canal was
      calculated and compared using t tests. RESULTS: Injecting viscoelastic material
      enlarged the area of Schlemm's canal adjacent to and 6.0 mm from the flap
      significantly more than not injecting viscoelastic material. While there was no
      difference between the viscoelastic materials in dilating Schlemm's canal at the
      flap, with Healon5 there was a small but statistically significantly greater
      dilation 6.0 mm from the flap. No full-thickness breaks in the trabecular
      meshwork were noted adjacent to or 6.0 mm from the flap. CONCLUSION: Injecting
      viscoelastic material significantly increased the cross-sectional area of
      Schlemm's canal and may play a role in the success of viscocanalostomy. Further
      study is needed to elucidate the mechanism of this procedure.

PMID- 11524204
TI  - In vitro adherence of Staphylococcus epidermidis to silicone punctual plugs and
      collagen implants.
AB  - PURPOSE: To evaluate in vitro adherence of Staphylococcus epidermidis to silicone
      punctal plugs and collagen implants. SETTING: Loyola University Medical Center,
      Maywood, Illinois, USA. METHODS: Silicone punctal plugs and collagen implants
      were exposed to S epidermidis (3 x 10(8) colony forming units/mL) for 0, 5, 30,
      and 60 minutes, rinsed in sterile saline, and processed for light, scanning
      (SEM), and transmission (TEM) electron microscopy. Scanning electron microscopy
      (x2000) was used to quantify bacteria/mm2 adhering to the devices. RESULTS: The
      mean S epidermidis/mm2 +/- (SD) adhering to each device were as follows:
      baseline, silicone punctal plug, 1593 +/- 899, and collagen implant, 7168 +/-
      2895 (P =.000, paired Student t test); 5 minutes, silicone punctal plug, 3833 +/-
      537, and collagen implant, 6571 +/- 2240 (P =.008); 30 minutes, silicone punctal
      plug, 13 988 +/- 9076, and collagen implant, 10 404 +/- 1731 (P =.2616); and 60
      minutes, silicone punctal plug, 12 644 +/- 10 402, and collagen implant, 11 748
      +/- 2685 (P =.8056). CONCLUSIONS: Staphylococcus epidermidis adhered
      significantly more to collagen implants than to silicone punctal plugs at 0 and 5
      minutes. No significant difference in bacterial adherence was seen at 30 and 60
      minutes. For both devices, bacterial adherence increased with increasing
      exposure.

PMID- 11524205
TI  - Extracellular matrix production of lens epithelial cells.
AB  - PURPOSE: To examine extracellular matrix (ECM) production of lens epithelial
      cells (LECs) and their regulation by cytokines. SETTING: Research Laboratory,
      International Intraocular Implant Training Center, Tianjin Medical University,
      People's Republic of China. METHODS: Bovine LECs were cultured with or without
      tumor necrosis factor alpha (TNF-alpha) and transforming growth factor beta2 (TGF
      beta2). Immunohistochemistry and in situ hybridization were used to detect the
      expression of ECM. The slides were quantified by computer analysis. RESULTS:
      Laminin expression was increased by both TNF-alpha and TGF-beta2. The expression
      of type IV collagen at the mRNA level was upregulated by TNF-alpha and TGF-beta2.
      Its protein expression was promoted by only TNF-alpha. CONCLUSIONS: Type IV
      collagen and laminin are the main components of the lens capsule. Their
      production of LECs could be increased by cytokines derived from the aqueous humor
      or LECs. This may lead to ECM deposition and capsule fibrosis during the
      development of posterior capsule opacification.

PMID- 11524206
TI  - Complications of foldable intraocular lenses requiring explantation or secondary
      intervention--2000 survey update.
AB  - A survey of the complications associated with foldable intraocular lenses (IOLs)
      that required explantation or secondary intervention was sent to members of the
      American Society of Cataract and Refractive Surgery and was also available to
      members of the European Society of Cataract and Refractive Surgeons. Preoperative
      data about visual acuity, patient signs and symptoms, and complications were
      assessed, and postoperative results and outcomes were analyzed. Complications and
      symptoms for each of the major groups of foldable IOLs explanted were tabulated
      separately: 3-piece monofocal silicone; 3-piece acrylic; 1-piece (plate-type)
      silicone; and multifocal silicone. A total of 259 surveys returned for
      evaluation. Accurate IOL power measurements as well as meticulous surgical
      technique, IOL loading and insertion, and proper patient counseling/selection
      remain the most important factors in avoiding complications with foldable IOLs.

PMID- 11524207
TI  - In vivo confocal microscopy of corneal epithelial ingrowth through a laser in
      situ keratomileusis flap buttonhole.
AB  - We report a case of epithelial ingrowth through a buttonhole 6 months after laser
      in situ keratomileusis. Elevation topography showed irregular astigmatism and an
      unreliable pachymetric map. In vivo confocal microscopy showed an epithelial
      basal cell mosaic with prominent borders and distinct nuclei. No corneal nerves
      were identified in any image. Cells in the anterior stroma possessed bright,
      reflective nuclei and appeared to form clusters. The interface between the
      stromal bed and the flap had formation of nests of fibrotic tissue and epithelial
      cells.

PMID- 11524208
TI  - Ultrastructure of the lamellar corneal wound after laser in situ keratomileusis
      in human eye.
AB  - A 30-year-old patient with keratoconus, a stable refraction, and normal central
      corneal thickness had laser in situ keratomileusis (LASIK). Six months later, she
      had uneventful penetrating keratoplasty for keratectasia. The lamellar LASIK
      interface could not be clearly identified by light microscopy. The corneal wound
      site did not stain for methyl metalloproteinase 1 or 2. Both the corneal flap
      undersurface and the stromal bed were devoid of interconnections and cells.
      Throughout the lamellar incision, including the laser-ablated zone, the surface
      was smooth on scanning electron microscopy. The collagen fibrils on both sides of
      the incision remained well aligned with one another, indicating good flap
      apposition. Under higher magnification transmission electron microscopy, some
      collagen fragments were found in the interface, especially adjacent to the hinge.
      The diameter of the collagen fibrils along the lamellar wound were identical to
      those farther from the incision. The absence of bridging collagen fibrils and
      cells between the flap undersurface and the stromal bed confirms the clinically
      known lack of wound repair at the interface and explains the easy separation of
      the flap from the stromal bed months after LASIK and the possible formation of an
      interface fluid pocket.

PMID- 11524209
TI  - Minimizing the risk of recutting with a Hansatome over an existing Automated
      Corneal Shaper flap for hyperopic laser in situ keratomileusis enhancement.
AB  - We report a case series of 4 eyes to discuss the intraoperative complications of
      recutting a laser in situ keratomileusis (LASIK) flap with a Hansatome
      microkeratome over an existing 160 microm Automated Corneal Shaper flap for the
      retreatment of hyperopia. In the eyes that were recut, slivers of stroma were
      apparent on reflection of the flap; the slivers were located centrally in the 180
      microm eye and peripherally in the 160 microm eyes. Recutting a flap for LASIK
      retreatment runs the risk of visually significant stromal irregularities.

PMID- 11524210
TI  - Traumatic phacocele.
AB  - We report a case of traumatic phacocele in a 42-year-old patient with a history
      of congenital glaucoma and bilateral goniotomies as an infant. Her left eye had
      little vision and poorly controlled intraocular pressure but was comfortable
      until her presentation after blunt trauma. Phacocele or subconjunctival
      dislocation of the crystalline lens is a rare consequence of blunt trauma,
      particularly in a patient whose only previous ocular surgery was goniotomy more
      than 40 years ago.

PMID- 11524211
TI  - Cataract surgery in a patient with Brown-McLean syndrome.
AB  - The Brown-McLean syndrome is defined by corneal edema that involves the
      peripheral 2.0 to 3.0 mm of cornea, sparing the central cornea. This syndrome is
      usually associated with previous cataract surgery but has been reported rarely in
      patients with other predisposing factors such as angle-closure glaucoma or
      spontaneous lens absorption with iridodonesis. We describe the clinical course of
      a 50-year-old man with myotonic dystrophy who had Brown-McLean syndrome with no
      identifiable predisposition for peripheral corneal edema. Although this syndrome
      appears to be the result of peripheral endothelial dysfunction, this patient was
      able to tolerate cataract extraction without developing central corneal edema.

PMID- 11524212
TI  - Adolescents and an AIDS vaccine?

PMID- 11524213
TI  - Adolescents' interpretations of conditional confidentiality assurances.
AB  - PURPOSE: To improve physicians' discussions of confidentiality policies with
      adolescent patients. METHOD: Fifty-three students completed private
      semistructured interviews designed to explore adolescents' interpretations of a
      statement explaining both the protections and limitations of confidentiality.
      RESULTS: Results suggest strategies for explaining conditional confidentiality in
      a way adolescents' understand and trust.

PMID- 11524214
TI  - Metformin to restore normal menses in oligo-amenorrheic teenage girls with
      polycystic ovary syndrome (PCOS).
AB  - PURPOSE: To describe our clinical experience in using Metformin combined with a
      high protein-low carbohydrate diet to restore normal menstrual cycles in teenaged
      females with polycystic ovary syndrome (PCOS). METHODS: To enter the study,
      patients had to have well-documented PCOS, be oligo- (six cycles or less in the
      preceding year) or amenorrheic (absence of menstrual cycles for 1 year), and not
      have exclusionary diseases or drugs. Accompanying a high protein-low carbohydrate
      diet, Metformin (1.5-2.55 g/day) was given for 10.5 +/- 6.4 months (range, 4.5
      26.5 months). Follow-up every 8-10 weeks for > or =6 months was scheduled with
      interval history, review of menstrual status, assessment of any Metformin-related
      side effects, brief physical examination, and determination of weight and blood
      pressure. RESULTS: All 11 girls had normal fasting blood glucose and
      glycohemoglobin. Pre-Metformin, five girls were amenorrheic, three had only one
      menstrual cycle in the previous year, and three had > or =6 cycles/year. With
      Metformin, 10 of 11 girls (91%) resumed regular normal menses; 39% of 38 follow
      up visits with regular normal menstrual cycles were ovulatory with normal luteal
      phase serum progesterone (> or =2.3 ng/mL). Of the 11 girls, nine (82%) lost
      weight; five girls lost > or =11 lb and seven lost > or =5 lb. After adjusting
      for weight reduction, with Metformin, estradiol and progesterone rose (p
      =.0014,.027, respectively) (changes consistent with resumption of regular normal
      menses), total plasma cholesterol fell (p =.026), and there was a downward trend
      in testosterone (p =.068). CONCLUSION: Metformin safely ameliorates the
      endocrinopathy of PCOS in previously oligo-amenorrheic teenage females with PCOS,
      facilitating resumption of normal menses in most girls.

PMID- 11524215
TI  - Health care information sources for adolescents: age and gender differences on
      use, concerns, and needs.
AB  - OBJECTIVES: To assess adolescents' sources of health care information, explore
      beliefs about topics which health care providers should address and about those
      which have been addressed, and identify topics that are embarrassing for
      adolescents to discuss with providers. METHODS: Participants included a
      nationally representative sample of 3153 boys and 3575 girls in 5th through 12th
      grades who completed the Commonwealth Fund survey. Data were analysed by
      inspection of percentages and bivariate associations. RESULTS: Boys (41.7%) and
      girls (58.4%) identified their mother as the primary resource for health care
      information. Younger boys and girls (grades five and six) were more likely than
      older boys and girls (grades 10 to 12) to ask their mother first about health
      issues (boys 54.4% vs. 35.2%; girls 71.7% vs. 46.4%). Doctors, nurses, or school
      nurses were also frequently identified as the first person asked about health
      issues (boys 23.9%, girls 18.2%). Most adolescents indicated that providers
      should address the following topics: drugs (65.0%); smoking (58.5%); sexually
      transmitted diseases (61.4%); alcohol use (56.2%); and good eating behaviors
      (56.8%). However, fewer adolescents reported that providers have actually
      discussed these issues with them; only 23.1% to 34.2% of adolescents reported
      having discussed the first four topics with them. Many youth noted that it would
      be embarrassing for them to discuss these issues with their providers.
      CONCLUSIONS: Adolescents report that parents and health care providers are key
      sources of health-related information. Although adolescents may be embarrass
      having discussions with their health care providers, adolescents do believe that
      these topics should be addressed. Adolescents' embarrassment about discussing
      sensitive health topics highlights the importance of providers initiating and
      facilitating these discussions.

PMID- 11524216
TI  - Contraceptive dispensing and selection in school-based health centers.
AB  - PURPOSE: To determine whether initiation of on-site dispensing of hormonal
      contraceptives (oral contraceptive pill, Depo-provera, and Norplant) in six urban
      school-based health centers reduced time to initial selection, and increased
      their consistent use among sexually active females. METHODS: Participants were
      sexually active females who received family planning care in a school year before
      (1994-1995 cohort) or after (1996-1997 cohort) the initiation of on-site
      dispensing. Data on contraception and sexual behavior were collected at each
      family planning visit. Cohorts were compared using Student's t-tests and Chi
      square tests, analysis of covariance, and logistic regression. RESULTS: About 59%
      of the 1994-1995 cohort selected hormonal contraceptives at the first or second
      visit; this increased to 72% of the 1996-1997 cohort (chi(2) = 11.3; p <.001).
      After adjustment for cohort differences, the 1996-1997 cohort consistently
      selected hormonal contraceptives a longer period of time, although the difference
      did not reach statistical significance (adjusted means: 1994-1995 cohort = 73
      days, 1996-1997 cohort = 81 days; t = 1.6, p <.10). CONCLUSION: Sexually active
      females receiving family planning care select methods of hormonal contraception
      sooner and somewhat more consistently when the clinics in their high schools can
      dispense contraceptives on-site.

PMID- 11524217
TI  - Where do adolescents get their condoms?
AB  - PURPOSE: To determine where adolescents obtain their condoms; the availability
      and accessibility of condoms; condom availability in relationship to different
      sexually transmitted disease (STD) rates; and the availability of safer sex
      information in places where condoms are sold. METHODS: We conducted a random
      digit-dialed telephone survey of 259 14-19-year-old adolescents in Monroe County,
      New York. Self-reported health services use, knowledge and use of confidential
      services, and where adolescents obtained or intended to obtain condoms were
      assessed. Research assistants visited all retail establishments in five areas of
      similar population size with gonorrhea rates from 887 to 12,427 per 100,000
      adolescents to assess how available and accessible condoms were in each store.
      Perceived access and actual condom availability and accessibility were compared
      using Chi-square and Student's t-tests. RESULTS: Trained interviewers dialed
      11,800 numbers in 1993, identifying 4449 (40%) households among 11,065 numbers
      reached successfully. Of these, 393 (8.8%) had eligible adolescents and 259 (66%)
      completed interviews. Most adolescents reported obtaining, or planning to obtain,
      condoms in stores rather than from free health care settings. Adolescents who
      have used condoms more often reported having obtained them without cost than
      having purchased them. Condoms were available at 101 (83%) of 122 stores
      identified. All drug stores and 75% of supermarkets sold condoms and displayed
      them openly. Most small grocery stores also sold condoms (92%), but were less
      likely to openly display them. No stores displayed or provided safer sex
      information. Areas with higher STD rates had more stores (p <.01), and more
      stores that sold condoms (p <.01). There was no difference in condom cost by
      area. CONCLUSIONS: Many adolescents obtain their condoms in retail stores. Condom
      accessibility varied by store type and area STD rate. Increasing condom
      visibility in private grocery stores may increase the accessibility of condoms to
      adolescents in areas with highest STD rates.

PMID- 11524218
TI  - Correct condom application among African-American adolescent females: the
      relationship to perceived self-efficacy and the association to confirmed STDs.
AB  - PURPOSE: To assess condom application ability and the relationship between
      perceived ability and demonstrated ability. Also, to examine the association
      between high-demonstrated condom application ability and recent sexual risk
      behaviors and laboratory-diagnosed sexually transmitted diseases (STDs) among
      African-American adolescent females. METHODS: A purposeful sample of sexually
      active African-American females (n = 522) completed a structured interview and
      provided vaginal swab specimens for STD testing. Subsequent to the interview,
      adolescents demonstrated their condom application skills using a penile model. A
      9-item scale assessed adolescents' perceived self-efficacy to apply condoms.
      Sexual risk behaviors assessed by interview were noncondom use at last
      intercourse and the last five intercourse occasions for steady and casual sex
      partners as well as any unprotected vaginal sex in the past 30 days and the past
      6 months. RESULTS: Approximately 28% of the sample tested positive for at least
      one STD and nearly 26% self-reported a history of STDs. Controlled analyses
      indicated that adolescents' self-efficacy for correct use was not related to
      demonstrated skill. Adolescents' demonstrated ability was not related to any of
      the sexual risk behaviors. Likewise, recent experience applying condoms to a
      partner's penis and demonstrated ability were not related to laboratory-diagnosed
      STDs or self-reported STD history. CONCLUSIONS: Adolescents may unknowingly be at
      risk for human immunodeficiency virus and STD infection owing to incorrect condom
      application. Further, high-demonstrated ability to apply condoms was not related
      to safer sex or STDs. Reducing sexual risk behaviors may require more than
      enhancing adolescent females' condom application skills and may require
      addressing other relational skills.

PMID- 11524219
TI  - Protective role of health values in adolescents' future intentions to use
      condoms.
AB  - PURPOSE: To examine the protective role of health values in adolescents'
      intentions to use condoms. METHODS: Two hundred thirty-six sexually active
      adolescents who were attending a municipal sexually transmitted diseases clinic
      were interviewed, using standardized and constructed instruments, regarding their
      previous condom use, health values, condom attitudes, social norms regarding
      condoms, self-efficacy regarding condoms, and intentions to use condoms in the
      future. Correlations and hierarchical multiple regression analyses were conducted
      to examine the direct and indirect effects of health values on intentions to use
      condoms. RESULTS: Health values were significantly correlated with intentions to
      use condoms with main and casual sexual partners, and accounted for a significant
      amount of variance in intentions to use condoms with casual sexual partners,
      after controlling for demographic variables, past condom use, and constructs from
      the Theory of Planned Behavior. Health values were also found to moderate the
      relationship between condom attitudes and intentions to use condoms with casual
      partners. CONCLUSIONS: Efforts to include health values as a protective factor in
      health behavior theory and risk-reduction interventions are warranted.

PMID- 11524220
TI  - Social cognitive correlates of sexual experience and condom use among 13- through
      15-year-old adolescents.
AB  - PURPOSE: To examine the role of self-efficacy, outcome expectancies, and
      perception of peer attitudes in the delay of onset of sexual activity among 13-
      through 15-year-old adolescents. We also explored the role of self-efficacy,
      outcome expectancies, and perception of friends' condom use behavior in
      explaining the use of condoms among sexually active adolescents. METHODS: This
      study was part of a larger cross-sectional study to evaluate personal
      characteristics and maternal factors associated with early initiation of sexual
      intercourse. Mothers and adolescents were recruited from a community-based
      organization that offered afterschool and summer programs for youth. Enrollment
      was limited to adolescents aged 13-15 years and their mothers. Mothers and
      adolescents completed separate interviews. For adolescents, the interviews
      included the assessment of the variables in the present study. Each interview
      lasted about 60 min and was conducted by a trained interviewer. Data were
      analyzed using descriptive statistics and regression analysis. The average age of
      the 405 adolescent participants was 13.86 years, and approximately 30% of them
      had engaged in sexual intercourse. Slightly more than half (56%) of participants
      were male, and 82% were African-American. RESULTS: Participants who were less
      likely to believe that their friends favored intercourse for adolescents and who
      held more favorable attitudes about the personal benefits of abstaining from sex
      were less likely to have initiated sexual intercourse. Among sexually active
      adolescents, those who expressed confidence in putting on a condom, and in being
      able to refuse sex with a sexual partner, and who expressed more favorable
      outcome expectancies associated with using a condom were more likely to use
      condoms consistently. CONCLUSIONS: Human immunodeficiency virus and pregnancy
      prevention programs should emphasize peer influences in both the initiation of
      sexual intercourse and the use of safer sex practices among sexually active
      adolescents, as well as personal attitudes about consequences to self and
      confidence in negotiating safer sex practices with one's partner.

PMID- 11524221
TI  - The importance of hepatitis B vaccination among adolescents.
AB  - OBJECTIVE: To examine whether teens who have received an education about
      hepatitis B and demonstrated content mastery can apply this knowledge to evaluate
      their own risk of acquiring hepatitis B. METHODS: Nine hundred forty-three
      participants received a standard education and completed a questionnaire about
      hepatitis B; 769 participants who correctly answered the questions pertaining to
      risk factors for transmission participated. The questionnaire assessed
      demographic factors, self-reported risk behaviors, and attitudes toward hepatitis
      B and the immunization. Self-reported likelihood of acquiring hepatitis B and
      importance of hepatitis B immunization were measured on a 10-point Likert scale
      and served as outcome variables. Relationships were analyzed using frequency
      analysis, Mann-Whitney U and Kruskal-Wallis analysis of variance. RESULTS:
      Participants who were nonwhite (p <.001), had their bills paid by Medicaid (p
      =.007), were lower academic achievers (p =.011), had had sexual intercourse (p
      =.003), and had had a sexually transmitted disease (STD) (p =.028) were more
      likely to report that the hepatitis B immunization was more important to their
      health. Participants who reported they had smoked tobacco (p =.018) or consumed
      alcohol (p =.001) recently, had had sexual intercourse (p <.001), or had been
      diagnosed with an STD (p <.001) were more likely to report being at higher risk
      for acquiring hepatitis B. CONCLUSIONS: Most teens considered the hepatitis B
      immunization important to their health. Most adolescents did not think they were
      at significant risk for contracting hepatitis B; however, teens who reported
      increased individual risk factors also reported increased perceived risk of
      disease.

PMID- 11524222
TI  - Adolescent pregnancy 1 year later: the effects of abortion vs. motherhood in
      Northeast Brazil.
AB  - PURPOSE: To determine social and behavioral consequences of pregnancy and how
      these differed according to the pregnancy outcome (live birth or abortion) 1 year
      after the event. METHODS: This was a prospective study of two groups of young
      women aged 12-18 years, one attending prenatal services and the other admitted
      for abortion complications at the same hospital in northeast Brazil. Adolescents
      who gave birth were subsequently classified as having intended or unintended
      pregnancies, and those who aborted were divided between those who terminated
      their pregnancies and those who miscarried. Baseline data were collected between
      1995 and 1997 from all teens who met the eligibility criteria. Information was
      collected through one-on-one interviews using a questionnaire that was structured
      and precoded. Multiple logistic regression was used to identify characteristics
      that predicted outcomes at 1 year. RESULTS: Teens who terminated their
      pregnancies were the most likely to be in school or working 1 year later. They
      also showed the greatest increase in self-esteem. The young mothers, however, had
      the highest self-esteem but perceived the impact of pregnancy on their lives as
      being more negative than they did initially. Group affiliation was not associated
      with the quality of partner relationships, which tended to deteriorate over time.
      The young mothers used contraception at 1 year at higher rates and had
      experienced fewer subsequent pregnancies than the two abortion groups.
      CONCLUSIONS: The experience of adolescent pregnancy for this group of teens
      produced mixed findings, some more negative than others. Interventions to
      decrease the adolescent's desire to have a baby will have to be tailored
      differently from those designed to prevent an unintended pregnancy, but both are
      needed.

PMID- 11524224
TI  - Acquisition, segmentation and tracking of the cerebral vascular tree on 3D
      magnetic resonance angiography images.
AB  - This paper presents a method for the detection, representation and visualisation
      of the cerebral vascular tree and its application to magnetic resonance
      angiography (MRA) images. The detection method is an iterative tracking of the
      vessel centreline with subvoxel accuracy and precise orientation estimation. This
      tracking algorithm deals with forks. Centrelines of the vessels are modelled by
      second-order B-spline. This method is used to obtain a high-level description of
      the whole vascular network. Applications to real angiographic data are presented.
      An MRA sequence has been designed, and a global segmentation of the whole
      vascular tree is realised in three steps. Applications of this work are accurate
      3D representation of the vessel centreline and of the vascular tree, and
      visualisation. The tracking process is also successfully applied to 3D contrast
      enhanced MR digital subtracted angiography (3D-CE-MRA) of the inferior member
      vessels. In addition, detection of artery stenosis for routine clinical use is
      possible due to the high precision of the tracking algorithm.

PMID- 11524225
TI  - Segmentation of brain 3D MR images using level sets and dense registration.
AB  - This paper presents a strategy for the segmentation of brain from volumetric MR
      images which integrates 3D segmentation and 3D registration processes. The
      segmentation process is based on the level set formalism. A closed 3D surface
      propagates towards the desired boundaries through the iterative evolution of a 4D
      implicit function. In this work, the propagation relies on a robust evolution
      model including adaptive parameters. These depend on the input data and on
      statistical distribution models. The main contribution of this paper is the use
      of an automatic registration method to initialize the surface, as an alternative
      solution to manual initialization. The registration is achieved through a robust
      multiresolution and multigrid minimization scheme. This coupling significantly
      improves the quality of the method, since the segmentation is faster, more
      reliable and fully automatic. Quantitative and qualitative results on both
      synthetic and real volumetric brain MR images are presented and discussed.

PMID- 11524226
TI  - CURVES: curve evolution for vessel segmentation.
AB  - The vasculature is of utmost importance in neurosurgery. Direct visualization of
      images acquired with current imaging modalities, however, cannot provide a
      spatial representation of small vessels. These vessels, and their branches which
      show considerable variations, are most important in planning and performing
      neurosurgical procedures. In planning they provide information on where the
      lesion draws its blood supply and where it drains. During surgery the vessels
      serve as landmarks and guidelines to the lesion. The more minute the information
      is, the more precise the navigation and localization of computer guided
      procedures. Beyond neurosurgery and neurological study, vascular information is
      also crucial in cardiovascular surgery, diagnosis, and research. This paper
      addresses the problem of automatic segmentation of complicated curvilinear
      structures in three-dimensional imagery, with the primary application of
      segmenting vasculature in magnetic resonance angiography (MRA) images. The method
      presented is based on recent curve and surface evolution work in the computer
      vision community which models the object boundary as a manifold that evolves
      iteratively to minimize an energy criterion. This energy criterion is based both
      on intensity values in the image and on local smoothness properties of the object
      boundary, which is the vessel wall in this application. In particular, the method
      handles curves evolving in 3D, in contrast with previous work that has dealt with
      curves in 2D and surfaces in 3D. Results are presented on cerebral and aortic MRA
      data as well as lung computed tomography (CT) data.

PMID- 11524227
TI  - Atlas-assisted localization analysis of functional images.
AB  - OBJECTIVE: This paper introduces a method for localization analysis of functional
      images assisted by a brain atlas. The usefulness of the system developed, based
      on this method, is analyzed for human brain mapping and neuroradiology. MATERIALS
      AND METHODS: We use an enhanced and extended electronic Talairach-Tournoux brain
      atlas, containing segmented and labeled subcortical structures, Brodmann's areas,
      and gyri. The brain atlas serves as a tool for anatomy referencing, segmentation,
      labeling, registration, and providing 3D anatomical relationships. The process of
      localization analysis is decomposed into five steps: data loading, feature
      extraction, data normalization, identification and editing of loci, and getting
      labels and values. This analysis is supported by near real-time data-to-atlas
      warping based on the Talairach transformation. Metanalysis is enabled by merging
      the current and external lists of activation loci. RESULTS: We have designed,
      developed, tested, and deployed a commercial system for atlas-assisted
      localization analysis of functional images. This is the first system where an
      electronic version of the Talairach-Tournoux brain atlas is used interactively
      for analysis of functional images. This system runs on personal computers and
      provides functions for a rapid normalization of anatomical and functional
      volumetric data, data segmentation and labeling, readout of Talairach
      coordinates, and data display. It also is empowered with several unique features
      including: interactive warping facilitating fine tuning of the data-to-atlas fit,
      a backtracking mechanism to compensate for missing landmarks and enhancing the
      outcome of the overall process of data analysis, navigation on the triplanar
      formed by the data and the atlas, multiple-images-in-one display with atlas
      anatomy-function blending, a fast locus-controlled generation of results, editing
      of loci, multiple label display, and saving and reading of loci. The system
      normalizes a single image in near real-time (0.7 s), so analysis of anatomical
      and functional datasets can be done on-the-fly regardless of the number of
      slices. The same task performed by the state-of-the-art non-linear registration
      methods may require up to several days. CONCLUSIONS: The system is a useful tool
      for atlas-assisted localization analysis and a helpful adjunct to
      function/location metanalysis in human brain mapping research. It is also a step
      forward in bringing the atlas and the clinical data together within a practical
      and powerful solution that is fast and flexible, yet low-cost and affordable.

PMID- 11524228
TI  - Creating a high-resolution spatial/symbolic model of the inner organs based on
      the Visible Human.
AB  - Computerized three-dimensional models of the human body, based on the Visible
      Human Project of the National Library of Medicine, so far do not reflect the rich
      anatomical detail of the original cross-sectional images. In this paper, a
      spatial/symbolic model of the inner organs is developed, which is based on more
      than 1000 cryosections and congruent fresh and frozen CT images of the male
      Visible Human. The spatial description is created using color-space segmentation,
      graphic modeling, and a matched volume visualization with subvoxel resolution. It
      is linked to a symbolic knowledge base, providing an ontology of anatomical
      terms. With over 650 three-dimensional anatomical constituents, this model offers
      an unsurpassed photorealistic presentation and level of detail. A three
      dimensional atlas of anatomy and radiology based on this model is available as a
      PC-based program.

PMID- 11524229
TI  - What is the role of melatonin within the anterior pituitary?
AB  - The pineal hormone, melatonin, is uniquely defined by its role as hormonal time,
      but the processes whereby cells extract temporal information from the melatonin
      signal are not understood. Melatonin receptors are expressed in the pars
      tuberalis (PT) and, during fetal and perinatal life, in the pars distalis (PD).
      Functional studies suggest that the PT mediates the seasonal effects of melatonin
      on prolactin secretion, whilst the PD may be involved in photoperiodic
      programming of the developing gonadotrophic axis. To understand these effects at
      the cellular level we need to know the phenotype of melatonin-responsive cells.
      This review summarises current understanding in this area, and highlights present
      shortcomings. A case is presented for exploring the hypothesis that there is a
      functional association between melatonin receptor expression and cell
      differentiation in the anterior pituitary.

PMID- 11524230
TI  - Expression of the adrenomedullin binding protein, complement factor H, in the
      pancreas and its physiological impact on insulin secretion.
AB  - Adrenomedullin (AM) is a ubiquitous peptide hormone which, among other functional
      roles, reduces insulin secretion in the pancreas. Recently we have described the
      interaction between AM and the complement regulator protein factor H, which
      results in mutual modulation of their respective functions. Here we identify the
      expression of factor H in the beta cells of the rat pancreatic islets by
      immunohistochemistry and multiple immunofluorescence followed by confocal
      microscopy. In addition, double immunogold staining under the electron microscope
      showed coexistence of insulin and factor H immunoreactivities within the same
      secretory granules; interestingly, factor H staining was found in the electron
      lucent haloes whereas the insulin antibody labeled preferentially the dense
      cores. The existence of factor H mRNA in the pancreas was confirmed by RT-PCR and
      in situ hybridization. The function of factor H in the pancreas was investigated
      with an insulin secretion assay. Addition of factor H to freshly isolated islets
      in the presence of AM resulted in a further reduction in insulin secretion with a
      concomitant elevation of cAMP, suggesting that factor H increases AM function in
      glucose homeostasis. The expression of factor H in the pancreas may play other
      important roles such as protection against complement-mediated cell lysis.

PMID- 11524232
TI  - Decreased galanin mRNA levels in growth hormone-releasing hormone neurons after
      perinatally induced growth retardation.
AB  - Intrauterine growth retardation (IUGR) is associated with persistent postnatal
      growth retardation accompanied by dysfunction of the hypothalamic components of
      the growth hormone (GH) axis. At the adult stage, this is reflected by increased
      somatostatin (SS) and decreased neuropeptide Y (NPY) mRNA levels, whereas the GH
      releasing hormone (GHRH) mRNA levels are normal and the output of GH remains
      unchanged. To extend our insight into the hypothalamic control of GH secretion in
      growth retarded rats, we determined galanin (GAL) mRNA levels at the adult stage
      of perinatally malnourished (i.e. IUGR and early postnatally food restricted)
      rats. Analyses included comparison of GAL mRNA levels in GHRH neurons in
      perinatally malnourished adult rats using a semi-quantitative double labeling in
      situ hybridization technique. We report that IUGR is accompanied by a 60%
      decrease in GAL mRNA levels in all GHRH neurons in the male IUGR group whereas a
      tendency towards a decrease was observed in the male early postnatally food
      restricted (FR) group. These effects became more pronounced when the analysis was
      restricted to GHRH neurons coexpressing GAL mRNA i.e. decreased GAL mRNA levels
      were seen in both male and female IUGR rats and in FR males. These data show that
      GAL mRNA levels in GHRH neurons are persistently decreased after perinatal
      malnutrition. Taking these results together with our previous data on SS, NPY and
      GHRH mRNA levels, we can conclude that IUGR leads to a reprogramming of the
      hypothalamic regulation of GH secretion.

PMID- 11524231
TI  - GRO-alpha in normal and pathological thyroid tissues and its regulation in
      thyroid-derived cells.
AB  - Thyroid glands affected by Graves' disease (GD) show striking leukocytic
      infiltration, mainly by T-cells. The mechanisms by which the various leukocytes
      are maintained in the thyroid are unknown. Growth-regulated oncogene-alpha (GRO
      alpha) in interaction with its receptor CXCR2 is a chemoattractant for both T
      cells and neutrophils and may be one of the chemokines involved in the cell
      maintenance. GRO-alpha and CD18 mRNA as a marker of leukocytic infiltration were
      quantified in thyroid tissue using competitive RT-PCR. We found very high GRO
      alpha mRNA levels in all thyroid tissues. In GD patients (n=16), the GRO-alpha
      mRNA did not correlate with the CD18 mRNA level or thyroid peroxidase and TSH
      receptor antibodies in patients' sera. In thyroid autonomy (n=10), the GRO-alpha
      mRNA levels were significantly lower in autonomous single adenomas compared with
      the corresponding normal tissue. In order to define the cellular source of GRO
      alpha mRNA and protein, we examined various thyroid-derived cells. Thyrocytes,
      thyroid-derived leukocytes and fibroblasts showed basal GRO-alpha mRNA and
      protein expression, which was remarkably upregulated by different stimuli in
      vitro. The expression of GRO-alpha by thyroid carcinoma cell lines confirms that
      thyrocytes may actually produce GRO-alpha. As shown by flow cytometry and
      immunohistology, CD68+ monocytes/macrophages are the only cell population
      strongly expressing CXCR2 in the thyroid.

PMID- 11524233
TI  - Repeated in vivo determinations of bone mineral density during parathyroid
      hormone treatment in ovariectomized mice.
AB  - The recent development of different genetically modified mice with potentially
      interesting bone phenotypes has increased the demand for effective non-invasive
      methods to evaluate effects on bone of mice during growth and development, and
      for drug evaluation. In the present study, the skeleton was analyzed by repeated
      in vivo scans using dual energy X-ray absorptiometry (DXA) and peripheral
      quantitative computed tomography (pQCT). Ovariectomized (ovx) mice treated with
      parathyroid hormone (PTH) were used as an animal model to evaluate these two
      techniques at different times after the onset of treatment. Female mice (6 weeks
      of age) were allocated randomly to four groups: (1) sham-operated+vehicle; (2)
      ovx+vehicle; (3) sham-operated+PTH(1-84) 150 microg/kg per day; (4) ovx+PTH. Six
      weeks after ovariectomy the drug treatment began and was continued for 8 weeks.
      The total body bone mineral content (BMC) and total body areal bone mineral
      density (BMD) were measured by DXA. Ovariectomy reduced total body BMC and total
      body areal BMD by 6.2+/-1.7% and 2.6+/-0.9% respectively. No effect of PTH on
      total body BMC was seen during the treatment period. The trabecular volumetric
      BMD was measured by pQCT. Ovariectomy reduced the trabecular volumetric BMD by
      52+/-6.7%. The pQCT technique detected a clear effect on trabecular volumetric
      BMD after 2 weeks of PTH treatment (ovx 94+/-29% and sham-operated 46+/-10% more
      than vehicle-treated). The cortical bone was measured in a mid-diaphyseal pQCT
      scan of the tibia. Ovariectomy reduced the cortical BMC by 9+/-2%. PTH treatment
      for 8 weeks increased cortical BMC in ovx mice. In conclusion, the pQCT technique
      is more sensitive than the DXA technique in the detection of bone loss after
      ovariectomy and increased bone mass after PTH treatment in mice. Notably, the
      pQCT, but not the DXA, technique detected a dramatic effect as early as after 2
      weeks of PTH treatment. Dynamic pQCT measurements will be useful for monitoring
      skeletal changes during growth and development, and for drug evaluation in mice.

PMID- 11524234
TI  - Effect of diethylstilbestrol on cell proliferation and expression of epidermal
      growth factor in the developing female rat reproductive tract.
AB  - To evaluate mechanisms of cell proliferation in the fetal female rat reproductive
      tract, diethylstilbestrol (DES) effects on cell division and estrogen receptor
      (ER), epidermal growth factor (EGF) and EGF receptor (EGF-R) expressions were
      determined from gestational day (GD) 15.5 to 21.5. Reproductive tracts were
      evaluated within three regions along the Mullerian duct axis; these were
      proximal, middle and caudal, which differentiate into oviduct, uterus and upper
      vagina respectively. In fetuses from non-treated dams, epithelial and mesenchymal
      proliferation, as evaluated by 5-bromo-2'-deoxyuridine incorporation, was
      decreased with development in all regions of the Mullerian duct. EGF levels were
      determined by immunohistochemistry. Mullerian epithelial EGF immunoreactivity was
      intense in the proximal and middle regions on GDs 15.5 and 17.5. EGF staining
      remained intense only in the proximal epithelia by GD 19.5 and was weak in the
      caudal epithelium, but substantially reduced throughout epithelia in all regions
      by GD 21.5. Thus, decreased cell proliferation correlated with decreased EGF
      expression in the developing Mullerian duct. DES (100 microg/kg body weight) was
      injected from GD 15 to 19 and female fetuses were collected on GD 19.5. DES
      increased Mullerian duct cell proliferation in the proximal epithelium and
      mesenchyme but decreased it in the caudal epithelium compared with oil-treated
      controls. No proliferative DES effect was observed in any cell type in the middle
      region. Mullerian duct EGF immunoreactivity was suppressed by DES compared with
      oil. Competitive RT-PCR indicated DES also decreased mRNAs for EGF, ERbeta1 and
      ERbeta2, but not ERalpha and EGF-R. These results indicate EGF may be an
      important regulatory factor of Mullerian duct cell proliferation, and that DES
      may alter cell proliferation by disrupting normal EGF, ERbeta1 and ERbeta2
      expression in the developing female rat reproductive tract.

PMID- 11524235
TI  - Comparisons of the effects of tamoxifen, toremifene and raloxifene on enzyme
      induction and gene expression in the ovariectomised rat uterus.
AB  - This study compares the actions of oestradiol, tamoxifen, toremifene and
      raloxifene on enzyme and gene expression in uterine tissues of ovariectomised
      rats over 72 h. The time-course for the induction of ornithine decarboxylase by
      the compounds showed a rapid biphasic response, while for creatine kinase brain
      type (BB) there was a continued increase over 72 h. The efficacy of induction
      showed that, with both markers, oestradiol gave the highest induction level,
      followed by tamoxifen or toremifene and then raloxifene. RT-PCR demonstrated that
      all compounds decreased oestrogen receptor (ER) alpha, ERbeta and ERbeta2 gene
      expression, 8-24 h after the first dose, suggesting that down-regulation of ER is
      not the primary cause of the difference in efficacy between these compounds.
      Using cDNA arrays, expression of 512 genes was examined in the uteri of
      oestradiol- or tamoxifen-treated rats. Both compounds resulted in the up
      regulation of heat-shock protein 27, telomerase-associated protein 1 and
      secretin. However, most surprising was the marked down-regulation of Wilms'
      tumour and retinoblastoma genes. We speculate that this may result in a loss of
      regulation of the transition from the G1 to the S phase in the cell cycle and may
      make cells more vulnerable to the carcinogenic effects of tamoxifen in this
      tissue.

PMID- 11524236
TI  - Granulosa cells of the cumulus oophorus are different from mural granulosa cells
      in their response to gonadotrophins and IGF-I.
AB  - There are two types of granulosa cells: those which surround the oocyte are
      cumulus cells (CC) and those which surround the antrum are mural granulosa cells
      (MGC). These cells are under the influence of several hormones and growth
      factors, the most important of which are gonadotrophins and IGF-I. In this
      article, we report novel observations on the differences between these two types
      of granulosa cells and their interaction with gonadotrophins and IGF-I. We were
      able to conduct physiological studies on the role of IGF-I by using an analogue
      of IGF-I which does not bind to IGF-I-binding proteins (LR3-IGF-I). Immature rats
      received saline, equine chorionic gonadotrophin (eCG), LR3-IGF-I or eCG plus LR3
      IGF-I by infusion using a pump from 24-29 days of age. The rats were killed and
      the ovaries removed. Surface follicles were punctured and MGC and oocyte cumulus
      complexes were removed. These were cultured in saline (control) and in three
      different doses of FSH. Cell replication was assessed by 3H-thymidine
      incorporation and differentiation was evaluated by the measurement of
      progesterone secretion. It was noted that CC replicated ten times more than MGC.
      Similarly, progesterone secretion by CC was six times more than by MGC. In vivo
      exposure to gonadotrophins (eCG) positively influenced in vitro treatment with
      FSH in both cell types. This phenomenon was observed in both cell replication and
      progesterone secretion. The IGF-I analogue had a positive effect on cell
      replication of MGC but a negative effect on the cell replication of CC. With
      respect to progesterone secretion, the IGF-I analogue had a negative effect on CC
      but a positive effect on MGC. In conclusion, CC behaved differently from MGC in
      response to gonadotrophins and the IGF-I analogue. IGF-I and FSH acted
      additively, synergistically or antagonistically in different circumstances.

PMID- 11524237
TI  - Coeliac ganglion adrenergic activity modifies ovarian progesterone during
      pregnancy: its inter-relationship with LH.
AB  - Most of the fibres that constitute the superior ovarian nerve (SON) originate at
      the neuronal bodies of the coeliac ganglion and innervate rat ovarian stroma
      cells. The purpose of this work was to study the part played by innervation on
      ovarian release of progesterone on day 15 and at the end of pregnancy in an
      integrated in vitro system known as the coeliac ganglion-SON-ovary system. We
      also investigated, in the same system, whether there is some kind of inter
      relationship between the effect of adrenergic agents and LH on progesterone
      release on day 15 of pregnancy. The coeliac ganglion and the ovary were incubated
      in separate compartments, linked by the SON. The ovary was immersed in 2 ml
      buffer solution (ovarian compartment) and the coeliac ganglion was immersed in 2
      ml of a different buffer solution (ganglion compartment). Under these conditions,
      the accumulation of progesterone in the ovarian compartment medium was used as an
      endpoint. Conditions were standardised on day 15 of pregnancy, when the decrease
      in the release of ovarian progesterone caused by non-specific stimulation on the
      ganglion with KCl (56 mM) demonstrated the functional integrity of the system.
      Neural influence was evaluated by the addition of adrenergic agents at a
      concentration of 10(-6)M to the coeliac ganglion. On day 15 of pregnancy,
      noradrenaline and propranolol increased progesterone release while phentolamine
      diminished it. The existence of ganglionic tone was assessed by analysing
      progesterone basal levels at different stages of pregnancy. The highest secretion
      of progesterone was found to take place on day 15, diminishing as pregnancy
      advanced. In addition, adrenergic neural participation was studied during the
      physiological luteolysis occurring at the end of pregnancy. Major findings were
      that noradrenaline increased ovarian accumulation of progesterone on day 19 and
      decreased it on day 20, while propranolol and phentolamine diminished
      progesterone release on both days. In additional studies, some neuroendocrine
      aspects were investigated at a peripheral level. The addition of LH only to the
      ovarian compartment did not affect progesterone secretion. However, when LH in
      the ovarian compartment was accompanied by noradrenaline, propranolol or
      phentolamine in the ganglion compartment, the release of progesterone decreased.
      It can be concluded that modifications of the neural state of the coeliac
      ganglion affect ovarian progesterone secretion and the physiology of pregnancy
      via the SON. The results may confirm that the coeliac ganglion-SON-ovary system
      provides a direct link between the autonomic nervous system and physiological
      events during pregnancy.

PMID- 11524238
TI  - Insulin-like growth factor-binding protein-1 in umbilical artery and vein of term
      fetuses with signs suggestive of distress during labor.
AB  - Insulin-like growth factor-binding protein-1 (IGFBP-1) is believed to be an
      inhibitory factor for fetal growth. The regulation of IGFBP-1 secretion in the
      fetus is uncertain, although insulin and oxygen tension (PO2) and saturation are
      thought to play a role. We studied IGFBP-1 levels in umbilical cord artery (UA)
      and vein (UV) of 98 singleton fetuses at term with clinical signs of distress
      during labor, i.e. meconium-stained liquor or/and an abnormal fetal heart rate
      tracing. Blood gas values and serum C-peptide and IGFBP-1 concentrations were
      measured in both UA and UV. Twenty-five fetuses had an UA pH<7.20. The
      concentrations of IGFBP-1 were similar in UA and UV and were highly correlated
      (r=0.98). IGFBP-1 levels were inversely correlated with birth weight, with
      increased concentrations in small-for-gestational age fetuses (< or =10th weight
      percentile). IGFBP-1 levels were negatively correlated with C-peptide
      concentrations, and remained so after correction for birth weight (r=-0.37 for
      both UA and UV; P<0.001); more specifically, IGFBP-1 levels were increased in the
      lowest C-peptide quartile (<0.23 nmol/l) compared with the other quartiles. In
      addition, IGFBP-1 levels were inversely correlated with PO(2) values (r=-0.39 in
      UA and r=-0.34 in UV; P<0.001); quartiles of UA and UV PO2 showed a gradual
      increase in IGFBP-1 concentrations with lower PO2 values. A regression model with
      C-peptide and PO2 values as independent variables predicted IGFBP-1
      concentrations (R2 of model was 0.25 and 0.22 for UA and UV respectively;
      P<0.001). Other blood gas values (pH, PCO2, HCO3- and base deficit) did not
      correlate with IGFBP-1 levels. The data of this study indicate that serum IGFBP-1
      levels in term fetuses are determined by both insulin and PO2 levels, and suggest
      that acute hypoxemia stimulates IGFBP-1 secretion in the fetus.

PMID- 11524239
TI  - Dietary soy-phytoestrogens decrease testosterone levels and prostate weight
      without altering LH, prostate 5alpha-reductase or testicular steroidogenic acute
      regulatory peptide levels in adult male Sprague-Dawley rats.
AB  - Nutritional factors, especially phytoestrogens, have been extensively studied for
      their potential beneficial effects against hormone-dependent and age-related
      diseases. The present study describes the short-term effects of dietary
      phytoestrogens on regulatory behaviors (food/water intake, locomotor activity and
      body weight), prostate weight, prostate 5alpha-reductase enzyme activity,
      reproductive hormone levels, and testicular steroidogenic acute regulatory
      peptide (StAR) levels in adult Sprague-Dawley rats. Animals were fed either a
      phytoestrogen-rich diet containing approximately 600 microg/g isoflavones (as
      determined by HPLC) or a phytoestrogen-free diet. After 5 weeks of consuming
      these diets, plasma phytoestrogen levels were 35 times higher in animals fed the
      phytoestrogen-rich vs phytoestrogen-free diets. Body and prostate weights were
      significantly decreased in animals fed the phytoestrogen-rich diet vs the
      phytoestrogen-free fed animals; however, no significant change in prostate 5alpha
      reductase enzyme activity was observed between the treatment groups. Locomotor
      activity levels were higher in the phytoestrogen-rich vs the phytoestrogen-free
      animals during the course of the treatment interval. Plasma testosterone and
      androstenedione levels were significantly lower in the animals fed the
      phytoestrogen-rich diet compared with animals fed the phytoestrogen-free diet.
      However, there were no significant differences in plasma LH or estradiol levels
      between the diet groups. Testicular StAR levels were not significantly different
      between the phytoestrogen-rich vs the phytoestrogen-free fed animals. These
      results indicated that consumption of dietary phytoestrogens resulting in very
      high plasma isoflavone levels over a relatively short period can significantly
      alter body and prostate weight and plasma androgen hormone levels without
      affecting gonadotropin or testicular StAR levels. The findings of this study
      identify the biological actions of phytoestrogens on male reproductive
      endocrinology and provide insights into the protective effects these estrogen
      mimics exert in male reproductive disorders such as benign prostatic hyperplasia
      and prostate cancer.

PMID- 11524240
TI  - Androgen responsiveness of the pituitary gonadotrope cell line LbetaT2.
AB  - Androgens have a profound effect on the hypothalamic-pituitary axis by reducing
      the synthesis and release of the pituitary gonadotropin LH. The effect on LH is
      partly a consequence of a direct, steroid-dependent action on pituitary function.
      Although androgen action has been well studied in vivo, in vitro cell models of
      androgen action on pituitary gonadotropes have been scarce. Recently, an LH
      expressing cell line, LbetaT2, was generated by tumorigenesis targeted to the LH
      producing cells of the mouse pituitary. The purpose of these studies was to
      determine the presence of androgen receptor (AR) and establish its function in
      this cell line. RT-PCR analysis indicated that the LbetaT2 cell line expresses AR
      mRNA. Transient transfection assays, using the mouse mammary tumor virus (MMTV)
      promoter, showed that a functional AR is also present. Testosterone (TEST),
      dihydrotestosterone (DHT), 7alpha-methyl-19-nortestosterone (MENT), and
      fluoxymesterone (FLUOXY) increased reporter gene activity in the rank order of
      potencies MENT>DHT> TEST>FLUOXY. Additionally, activation of MMTV promoter
      activity by DHT in LbetaT2 cells was diminished by the AR antagonists casodex and
      2-hydroxy-flutamide, indicating that the effects of DHT are mediated through AR.
      In summary, these studies showed that the LbetaT2 cell line is a useful model for
      the evaluation and molecular characterization of androgen action in pituitary
      gonadotropes.

PMID- 11524241
TI  - Regulation of proliferation of prostate epithelial cells by 1,25-dihydroxyvitamin
      D3 is accompanied by an increase in insulin-like growth factor binding protein-3.
AB  - The biologically active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25
      (OH)2D3) has been shown to regulate the proliferation of human prostate
      epithelial cell lines. Since the insulin-like growth factor (IGF) system is
      involved in the transformation process of epithelial cells, the following study
      was undertaken to determine if the IGF system, in particular IGF binding protein
      3 (IGFBP-3), is altered by 1,25-(OH)2D3 in normal prostate epithelial cells as
      part of a mechanism for inhibition of transformation. Two cell systems were used
      in this study: (1) primary cultures of benign human prostate epithelial cells
      (PECs) and (2) an SV40-T immortalized prostate epithelial cell line (P153) that
      is non-tumorigenic. 1,25-(OH)2D3 was added to parallel sets of PECs and P153
      cells in addition to the presence or absence of IGF-I or des(1-3)IGF-I. Treatment
      with 1,25-(OH)2D3 resulted in significant growth inhibition of both PECs and P153
      cells. Furthermore, 1,25-(OH)2D3 inhibited IGF-induced proliferation, but this
      was partially reversed by high concentrations of IGF-I. Western ligand blots of
      condition media demonstrated a significant increase in IGFBP-3; likewise Northern
      blots demonstrated an increase in mRNA for IGFBP-3. Proliferation assays using an
      antibody designed to block the IGF-independent effects of IGFBP-3 failed to
      reverse the inhibitory effect of 1,25-(OH)2D3. Thus, IGFBP-3 acts in an IGF
      dependent manner to inhibit cell growth of benign prostate epithelial cells.

PMID- 11524242
TI  - Biochemical and functional analysis of a conserved IGF-binding protein isolated
      from rainbow trout (Oncorhynchus mykiss) hepatoma cells.
AB  - Rainbow trout (Oncorhynchus mykiss) serum contains several IGF-binding proteins
      (IGFBPs) that specifically bind to IGFs. The structures of these fish IGFBPs have
      not been determined and their physiological functions are poorly defined. In this
      study, we identified a 30 kDa IGFBP present in rainbow trout serum and secreted
      by cultured trout hepatoma cells. This IGFBP binds to IGFs but not to insulin.
      This IGFBP was purified to homogeneity using a three-step procedure involving
      Phenyl-Sepharose chromatography, IGF-I affinity chromatography and reverse-phase
      HPLC. Affinity cross-linking studies indicated that this IGFBP binds to IGF-I
      with a higher affinity than to IGF-II. N-terminal sequence analysis of the trout
      IGFBP suggests that it shares high sequence identity with that of human IGFBP-1
      in the N-terminal region. When added to cultured fish and human cells, the trout
      IGFBP inhibited IGF-I-stimulated DNA synthesis and cell proliferation in a
      concentration-dependent manner. The inhibitory effect of the fish IGFBP was
      comparable to those of human IGFBP-1 and -4. These results indicate that the
      IGFBP molecule is structurally and functionally conserved in evolutionarily
      ancient vertebrate species such as bony fish.

PMID- 11524243
TI  - p38 mitogen-activated protein (MAP) kinase but not p44/p42 MAP kinase is involved
      in prostaglandin E1-induced vascular endothelial growth factor synthesis in
      osteoblasts.
AB  - We investigated the mechanism underlying vascular endothelial growth factor
      (VEGF) synthesis stimulated by prostaglandin E1 (PGE1) in osteoblast-like MC3T3
      E1 cells. PGE1 induced the phosphorylation of both p44/p42 mitogen-activated
      protein (MAP) kinase and p38 MAP kinase. SB203580, a specific inhibitor of p38
      MAP kinase, inhibited the PGE1-stimulated VEGF synthesis as well as PGE1-induced
      phosphorylation of p38 MAP kinase. PD98059, an inhibitor of the upstream kinase
      that activates p44/p42 MAP kinase, which reduced the PGE1-induced phosphorylation
      of p44/p42 MAP kinase, had little effect on the VEGF synthesis stimulated by
      PGE1. AH-6809, an antagonist of the subtypes of the PGE receptor, EP1 and EP2, or
      SC-19220, an antagonist of EP1 receptor, did not inhibit the PGE1-induced VEGF
      synthesis. H-89, an inhibitor of cAMP-dependent protein kinase, and SQ22536, an
      inhibitor of adenylate cyclase, reduced the VEGF synthesis induced by PGE1.
      Cholera toxin, an activator of G(s), and forskolin, an activator of adenylate
      cyclase, induced VEGF synthesis. SB203580 and PD169316, another specific
      inhibitor of p38 MAP kinase, reduced the cholera toxin-, forskolin- or 8bromo
      cAMP-stimulated VEGF synthesis. However, PD98059 failed to affect the VEGF
      synthesis stimulated by cholera toxin, forskolin or 8-bromoadenosine-3',5'-cyclic
      monophosphate (8bromo-cAMP). SB203580 reduced the phosphorylation of p38 MAP
      kinase induced by forskolin or 8bromo-cAMP. These results strongly suggest that
      p44/p42 MAP kinase activation is not involved in the PGE1-stimulated VEGF
      synthesis in osteoblasts but that p38 MAP kinase activation is involved.

PMID- 11524244
TI  - Effects of transforming growth factors-alpha and -beta on proliferation and
      apoptosis of rat theca-interstitial cells.
AB  - Ovarian development, follicular growth and atresia require mechanisms regulating
      proliferation and death of ovarian cells including theca-interstitial (T-I)
      cells. Transforming growth factors-alpha and -beta (TGF-alpha and TGF-beta) are
      well recognized local modulators of T-I function. This study was performed to
      evaluate the effects of TGF-alpha and TGF-beta on ovarian T-I cell proliferation,
      differentiation and apoptosis. T-I cells from immature Sprague-Dawley rats were
      purified and incubated in chemically defined media. Proliferation was assessed by
      [3H]thymidine incorporation assay and by cell counting. Steroidogenically active
      cells were identified histochemically by detection of 3beta-hydroxysteroid
      dehydrogenase (3beta-HSD) activity. DNA was extracted and apoptosis was
      identified by detection of internucleosomal DNA cleavage producing the
      characteristic 'ladder pattern' of low-molecular weight (LMW) DNA following
      agarose gel electrophoresis. Quantification of apoptosis was carried out with the
      aid of 3'-end labeling of DNA fragments with [32P]-dideoxy-ATP. TGF-alpha and TGF
      beta stimulated [3H]thymidine incorporation by 2.2- to 3.1-fold and 1.7- to 3.4
      fold respectively (P<0.005). A combination of TGF-alpha and TGF-beta produced a
      synergistic increase in DNA synthesis by 6.7-fold (at 1 ng/ml of each TGF-alpha
      and TGF-beta; P<0.001) and tenfold (at 10 ng/ml of each TGF-alpha and TGF-beta;
      P<0.001). Cell counting revealed that TGF-alpha increased the total number of
      cells 2.8-fold and TGF-beta 2.8-fold. The combination of TGF-alpha and TGF-beta
      increased the total cell count 3.2-fold, compared with control (P<0.05). The
      percentage of the steroidogenically active cells was 37+/-9% (mean+/-s.e.m. ) in
      the control cultures, 50+/-5% in the presence of TGF-alpha, 42+/-8% in the
      presence of TGF-beta, and 47+/-13% in the presence of both TGF-alpha and TGF
      beta. TGF-alpha decreased apoptosis by 63+/-14% (P=0.02) while TGF-beta had no
      statistically significant effect. TGF-alpha in combination with TGF-beta produced
      the greatest inhibition of apoptosis by 73+/-8% (P=0.01). These findings
      demonstrate that TGF-alpha and -beta stimulate proliferation of both
      steroidogenically active and inactive T-I cells. Furthermore, TGF-alpha alone and
      in combination with TGF-beta protects T-I cells from apoptotic death. These
      effects of TGFs may be important in physiologic maintenance of ovarian
      mesenchymal growth and homeostasis as well as in pathophysiologic conditions
      associated with excessive growth of the T-I compartment, such as polycystic ovary
      syndrome.

PMID- 11524245
TI  - Transforming growth factor-beta2 antibody attenuates fibrosis in the experimental
      diabetic rat kidney.
AB  - Diabetic nephropathy is characterised by an increase in glomerular and tubular
      fibrosis that compromises kidney function. The transforming growth factor-betas
      (TGF-betas) have been shown to play a major role in fibrosis and we have shown
      that TGF-beta2, in particular, increases co-ordinately with fibrogenesis in the
      diabetic kidney. The aim of this study was to investigate the changes in
      expression of extracellular matrix molecules in the diabetic kidney, with and
      without systemic administration of a recombinant human monoclonal antibody to TGF
      beta2. Streptozotocin-induced diabetic rats were split into two groups. The first
      were treated with 5 mg/kg irrelevant control IgG4 (placebo) and the second
      treated with 5 mg/kg isoform-specific recombinant monoclonal anti-TGF-beta2 IgG4
      (termed CAT-152) systemically every second day for 14 days. A further group of
      six non-diabetic rats was also used as a control. Various biological parameters
      were measured daily throughout the experimental period, and on termination of the
      experiment at 14 days Western blotting was performed on kidney cortices for
      procollagen-I C-propeptide, which is an indicator of the rate of collagen-I
      synthesis within the kidney. In the placebo-treated diabetic rats, blood glucose,
      food consumption, urinary albumin excretion (UAE) and kidney weights were all
      significantly higher than in the non-diabetic group (P<0.05, n=24, by ANOVA). In
      the anti-TGF-beta2-treated diabetic rats, kidney weights and UAE levels were
      decreased when compared with those in placebo-treated diabetics. Western blotting
      for the procollagen-I C-propeptide in kidney cortices showed a significant
      increase in levels in placebo-treated diabetic rats compared with non-diabetic
      controls over the 14 day diabetic period, indicating initiation of fibrogenesis.
      By contrast, in anti-TGF-beta2-treated diabetic rats, levels of the propeptide
      remained at non-diabetic levels. In summary, a significant suppression of kidney
      fibrosis was seen in anti-TGF-beta2-treated diabetic rats, compared with placebo
      treated diabetic rats. We conclude that systemic delivery of CAT-152, a
      neutralising anti-TGF-beta2 antibody, during the acute stages of diabetic
      nephropathy reduces the rate of pathogenic fibrosis in the kidney.

PMID- 11524246
TI  - Programming hyperglycaemia in the rat through prenatal exposure to
      glucocorticoids-fetal effect or maternal influence?
AB  - In a previous study, we showed that exposure of rats to dexamethasone (Dex)
      selectively in late pregnancy produces permanent induction of hepatic
      phosphoenolpyruvate carboxykinase (PEPCK) expression and hyperglycaemia in the
      adult offspring. The mechanisms by which glucocorticoids cause this programming
      are unclear but may involve direct actions on the fetus/neonate, or
      glucocorticoids may act indirectly by affecting maternal postnatal nursing
      behaviour. Using a cross-fostering paradigm, the present data demonstrate that
      switching the offspring at birth from Dex-treated dams to control dams does not
      prevent induction of PEPCK or hyperglycaemia. Similarly, offspring born to
      control dams but reared by Dex-treated dams from birth maintain normal glycaemic
      control. During the neonatal period, injection of saline per se was sufficient to
      cause exaggeration in adult offspring responses to an oral glucose load, with no
      additional effect from Dex. However, postnatal treatment with either saline or
      Dex did not alter hepatic PEPCK activity. Prenatal Dex permanently raised basal
      plasma corticosterone levels, but under stress conditions there were no
      differences in circulating corticosterone levels. Likewise, Dex-exposed rats had
      similar plasma catecholamine concentrations to control animals. These findings
      show that glucocorticoids programme hyperglycaemia through mechanisms that
      operate on the fetus or directly on the neonate, rather than via effects that
      alter maternal postnatal behaviour during the suckling period. The hyperglycaemic
      response does not appear to result from abnormal sympathoadrenal activity or
      hypothalamic-pituitary-adrenal response during stress.

PMID- 11524247
TI  - Molecular genetic diagnostic program of multiple endocrine neoplasia type 2A and
      familial medullary thyroid carcinoma syndromes in Hungary.
AB  - Medullary thyroid carcinoma (MTC) occurs usually in sporadic form, but about a
      quarter of the cases are hereditary and appear as part of one of the multiple
      endocrine neoplasia type 2 (MEN2) syndromes. Mutations in the RET protooncogene
      are known to be the cause of the MEN2A and familial medullary thyroid carcinoma
      (FMTC) syndromes in the majority of the families. Direct DNA testing allows
      prophylactic thyroidectomy to be offered to individuals carrying a mutation in
      the above codons, and in mutation-negative cases it reduces the yearly screening
      related burden on family members at risk of the disease. By DNA sequencing and
      PCR-restriction fragment length polymorphisms, 65 MTC probands were examined for
      mutations in residues 609, 611, 618, 620 of exon 10, and in residues 634, 768,
      804 of exons 11, 13, and 14 respectively of the RET protooncogene. In our study,
      mutations in the above codons were detected in all of the 14 clinically MEN2A and
      FMTC families. One of these mutations, TGC609 TCC has not been reported
      previously. Of the 14 probands with the mutation, 25 relatives also had the
      identified mutation and 18 relatives proved to be non-carriers. Among the 51
      probands with clinically sporadic MTC, none was found to carry a mutation in the
      above positions even if indirect signs of MTC, pheochromocytoma or
      hyperparathyroidism could be detected in some families. The frequency of the
      TGC634AGC mutation is unexpectedly high in our samples, which can probably be
      attributed to a founder effect. We conclude that screening for mutations in these
      codons is effective in families fulfilling the strict clinical criteria of MEN2A
      or FMTC.

PMID- 11524248
TI  - Thyroid hormone stimulation of osteocalcin gene expression in ROS 17/2.8 cells is
      mediated by transcriptional and post-transcriptional mechanisms.
AB  - We investigated the mechanism of thyroid hormone regulation of osteocalcin (OC)
      gene expression in osteoblast-like cells (ROS 17/2.8). Treatment with tri
      iodothyronine (T3) (10(-8) M) increased OC mRNA levels by approximately 3-fold
      after 24 h and reached a maximum, approximately 5.4-fold, after 48 h. The mRNA
      levels of other bone-specific genes, alkaline phosphatase and osteopontin, were
      not affected by T3 treatment. Interestingly, T3 induction of OC mRNA varied
      according to cell density: approximately 4-fold at approximately 1x10(5)
      cells/dish and 1.5-fold at 40-60x10(5) cells/dish. The magnitude of OC mRNA
      induction by T3 was approximately 40% lower than induction by 1,25
      dihydroxyvitamin D3 (1,25D3) alone, and the combination of T3+1,25D3 did not
      further stimulate OC mRNA levels. T3 induction of OC mRNA was not affected by
      treatment with cycloheximide (10 microg/ml) for 5 h indicating that new protein
      synthesis is not required for the response. To study the half-life of OC mRNA,
      ROS 17/2.8 cells were incubated with actinomycin D. The basal half-life of OC
      mRNA (means+/-s.e.m.) was 6.4+/-0.2 h which was increased significantly with
      either T3 or 1,25D3 treatment to 10.9+/-0.6 h and 13.5+/-0.4 h respectively. T3
      modestly up-regulated the rate of OC gene transcription (1.7+/-0.2-fold) as
      determined by run-off assay. T3 did not induce a reporter construct containing
      the rat OC gene (rOC) 5'-flanking region (to -1750 bp) or the previously
      described rOC vitamin D response element, when transfected into ROS 17/2.8 cells.
      In conclusion, T3 up-regulates the OC mRNA expression in ROS 17/2.8 cells in a
      dose-, time- and cell confluence-dependent fashion, and does so by
      transcriptional and post-transcriptional mechanisms. The greater T3 induction of
      OC expression in ROS 17/2.8 cells at low cell density is consistent with findings
      of thyroid hormone action on bone development.

PMID- 11524249
TI  - Telomerase activity in primary cultures of normal adrenocortical cells.
AB  - Telomerase activity was measured in isolated cells from bovine and human adrenal
      cortex, in cells in primary culture, in cells in later passages in culture, and
      in cells genetically modified by expression of hTERT (human telomerase reverse
      transcriptase). Telomerase activity in freshly isolated bovine adrenocortical
      cells and in human adrenal cells from donors of various ages (6-79 years) was
      very low or undetected. However, primary bovine adrenocortical cell cultures were
      strongly positive for telomerase activity, and primary human adrenocortical cell
      cultures were weakly positive. Both cell types proliferate in primary culture but
      proliferation of bovine cells is much more vigorous. When primary bovine cells
      were subcultured to make successively secondary and tertiary cultures, telomerase
      activity declined strongly, and was undetected by the third passage. There was
      only a slight decrease in growth rate over this period. Levels of the telomerase
      RNA component did not change with passage number when assessed by semi
      quantitative competitive RT-PCR. When both bovine and human cells were infected
      with a retrovirus encoding hTERT, telomerase activity in the cells was very high.
      We conclude that in the adrenal cortex, as in some other tissues, TERT expression
      is regulated and upregulation of telomerase activity is associated with rapid
      proliferation in primary culture. Telomerase activity is not maintained, and
      introduction of TERT is required for stable telomerase activity and for
      immortalization.

PMID- 11524250
TI  - Association of phlebotomy and subcutaneous bolus injection of deferoxamine for
      the treatment of anemic patients with iron overload.

PMID- 11524251
TI  - A case of juvenile myelomonocytic leukemia presenting with a B-lymphoblastic
      immunophenotype.

PMID- 11524252
TI  - CD7(+) acute leukemia switching from a lymphoid to a myeloid phenotype.

PMID- 11524253
TI  - Urinary proteins in multiple myeloma: strong correlation with the indices of
      tumor burden.

PMID- 11524254
TI  - Bone marrow infiltrate by atypical histiocytic cells with cytoplasmatic Birbeck
      granules as initial presentation of an acute monoblastic leukemia.

PMID- 11524255
TI  - Polyclonal T-cell expansions in a HIV(+) patient with atypical cutaneous
      lymphoproliferative disorder, large granular lymphocyte proliferation and SENV
      infection.

PMID- 11524256
TI  - Childhood cutaneous natural killer/T lymphoma successfully treated with only one
      course of chemotherapy and incomplete tumor resection.

PMID- 11524257
TI  - Myelofibrosis with myeloid metaplasia with fatty bone marrow: report of a new
      case.

PMID- 11524258
TI  - Increased endothelial and platelet soluble selectins in heparin-induced
      thrombocytopenia associated with thrombosis.

PMID- 11524259
TI  - Genetic risk factors for thrombosis in a Basque population and its possible
      contribution to the analysis of a complex disease such as thrombophilia.

PMID- 11524260
TI  - Use of interleukin-11 after autologous stem cell transplant: report of three
      cases and a very brief review of the literature.

PMID- 11524261
TI  - Hypereosinophilia in acute lymphoblastic leukemia: an association to be
      remembered.

PMID- 11524262
TI  - Simultaneous occurrence of multiple myeloma and chronic myeloid leukemia.

PMID- 11524264
TI  - Sea-blue histiocytes in bone marrow of patient with Niemann-Pick disease type B.

PMID- 11524263
TI  - Immunoglobulin D plasmacytoma carrying aberrant expression of CD33 associated
      with aggressive visceral involvement.

PMID- 11524265
TI  - Adult T-cell leukemia showing different immunophenotypes in invaded organs.
AB  - We report here a case of adult T-cell leukemia (ATL) who presented acute renal
      failure and skin eruption. Renal and skin biopsies showed diffuse invasion of ATL
      cells. Furthermore, the surface phenotype of tumor cells taken from the bone
      marrow (BM) or peripheral blood (PB)(CD4-CD8-) differed from that of cells taken
      from the kidney or skin (CD4+CD8-). These findings suggested that CD4-CD8-ATL
      cells in the BM and PB had differentiated to CD4+CD8- cells in the kidney and
      skin.

PMID- 11524266
TI  - Prothrombotic study in full term neonates with arterial stroke.

PMID- 11524267
TI  - Acute myeloid leukemia precipitated by dengue virus infection in a patient with
      hemoglobin H disease.
AB  - We report a unique case of refractory acute myeloid leukemia (AML) precipitated
      by dengue virus induced marrow aplasia in a Chinese patient with hemoglobin (Hb)
      H disease. The quick temporal sequence of the three marrow abnormalities:
      hereditary hemoglobinopathy, reactive viral induced marrow change and malignant
      neoplastic process is highly unusual. Neither HbH disease nor viral induced
      marrow aplasia has known associations with AML. We propose that this unique case
      of AML may be caused by cytokine hyperstimulation in a stressed marrow.

PMID- 11524268
TI  - Successful treatment of hepatosplenic candidiasis in an elderly patient with
      acute myeloid leukemia using liposomal daunorubicin and fluconazole.
AB  - Fungal infections are an increasing cause of morbidity and mortality in patients
      with haematological malignancies. The organism most often responsible are Candida
      spp., particurarly Candida Albicans. This report describes our experience in a 63
      year-old man who developed symptoms of hepatosplenic candidiasis caused by
      Candida tropicalis after treatment for acute myeloid leukaemia (AML). The fungal
      infection was successfully controlled using fluconazole, and the patient has been
      disease-free for more than 11 months after antileukemic chemotherapy without any
      recurrence of Candida infections. Our experience suggests that AML and
      chemotherapy associated fungal infections can be controlled with an appropriate
      therapeutic regimen.

PMID- 11524269
TI  - Prophylaxis of transmission of hepatitis B virus with anti hepatitis B immune
      gamma ev in an allogeneic transplant of hematopoietic precursors.

PMID- 11524270
TI  - Bone marrow metastatic infiltration of a rabdoid pancreatic tumor.

PMID- 11524271
TI  - Complete haematological response with granulocyte colony stimulating factor (G
      CSF) and hydroxyurea in relapsed acute myeloid leukaemia (AML) of the elderly.

PMID- 11524272
TI  - Paget's disease associated with myelofibrosis and myeloid metaplasia--a common
      pathophysiology ?

PMID- 11524273
TI  - Transient erythoblastopenia in coeliac disease.

PMID- 11524285
TI  - Evolving concepts of cerebrospinal fluid physiology.
AB  - This article reviews the basic known functions of cerebrospinal fluid (CSF). The
      traditional concepts of CSF production and absorption are reviewed and recent
      challenges to these concepts are discussed. MR imaging studies have begun to
      elucidate the complex interaction between pulsatile CSF movement, bulk CSF flow,
      and intracranial compliance. An understanding of a variety of disorders,
      including hydrocephalus and Chiari malformations, continue to evolve as knowledge
      of CSF physiology is increased.

PMID- 11524286
TI  - Pathophysiologic consequences of hydrocephalus.
AB  - Hydrocephalus-induced damage is dependent on the rate and magnitude of
      ventricular dilatation, the proximity to the ventricle, and the developmental
      stage at which the disturbance occurs. It is mediated through a combination of
      mechanical, ischemic, and metabolic-toxic disturbances. Developmental processes,
      including myelin production, can be impaired. Periventricular axons are the
      primary target, however. The potential for reversal of damage by shunting
      diminishes as the duration and severity of hydrocephalus increases. Ancillary
      pharmacologic means for preventing hydrocephalus-induced brain damage are worth
      pursuing.

PMID- 11524287
TI  - Etiology and clinical course of hydrocephalus.
AB  - This article discusses the incidence, various causes, and different clinical
      presentations in children and adults with hydrocephalus.

PMID- 11524288
TI  - Diagnostic tools in hydrocephalus.
AB  - MR imaging is the premier imaging modality for diagnosing the various forms and
      causes of hydrocephalus. Although CT is satisfactory for imaging in the axial
      plane, MR imaging is capable of imaging in any plane to better demonstrate any
      cause of observation. MR imaging also is more sensitive than CT to interstitial
      edema (transependymal flow of cerebrospinal fluid [CSF]) and to the hyperdynamic
      CSF flow seen with shunt-responsive normal-pressure hydrocephalus (NPH). MR
      imaging also is sensitive to the presence of deep white matter ischemia that may
      contribute to the cause of the idiopathic form of NPH.

PMID- 11524289
TI  - Methods and complications in surgical cerebrospinal fluid shunting.
AB  - This article reviews the standard techniques of cerebrospinal fluid (CSF) shunt
      procedures and comments on advantages and disadvantages between various
      techniques. Complications of these procedures also are discussed.

PMID- 11524290
TI  - Shunt malfunctions.
AB  - Shunt failure remains a disheartening complication of shunt surgery. The number
      of adjustable factors in attempting to reduce the rate is small. The clinical
      presentation and timing of shunt malfunction are well documented. Although the
      shunt design trials have been negative to date, valves have important effects
      that have not as yet been translated to improved outcome.

PMID- 11524291
TI  - Epidemiology, diagnosis, treatment, and prevention of cerebrospinal fluid shunt
      infections.
AB  - Soon after cerebrospinal fluid (CSF) shunts became available in the late 1950s,
      infection was recognized as a serious complication of their use, although the
      bacterial cause of the infections and the way in which they arose was not
      clarified for a number of years. Subsequent research has since revealed their
      etiology and provided data that have improved the understanding of aspects of
      diagnosis, treatment, and prevention.

PMID- 11524292
TI  - The slit ventricle syndrome.
AB  - This article reviews the collection of entities that still are described as slit
      ventricle syndrome, discusses the various diagnoses, and reviews the
      investigation and treatment of children with small ventricles after ventricular
      shunting.

PMID- 11524293
TI  - Endoscopic methods of hydrocephalus treatment.
AB  - This article discusses the use of the endoscope in treatment of hydrocephalus
      without shunting. The selection of candidates for third ventriculostomy and
      choroid plexus coagulation are described together with the overall published
      rates of success with each technique. A summary of the nature and frequency of
      complications of third ventriculostomy are given after reviewing published data
      on over a thousand patients who have had the operation to date. The role of other
      endoscopic techniques, such as septal fenestration and decompression of
      obstructing cysts, also are discussed.

PMID- 11524294
TI  - Congenital hydrocephalus.
AB  - Congenital hydrocephalus results from a variety of causes, some of the most
      common include spina bifida (myelomeningocele), aqueductal stenosis, and Dandy
      Walker malformation. In addition, a number of cases result from genetic causes,
      other malformations, postinfectious, or neoplastic conditions. Outcome varies
      with cause but can be favorable. Most cases still are managed with shunting,
      although endoscopic modalities also can be considered.

PMID- 11524295
TI  - Posthemorrhagic hydrocephalus of infancy.
AB  - For a variety of anatomic and physiologic reasons, premature infants, especially
      those of very low birth weight, are most likely to sustain an intraventricular
      hemorrhage (IVH) and subsequent posthemorrhagic hydrocephalus (PHH). When to
      initiate treatment and what that treatment should be remains controversial. This
      article discusses the pathophysiology and clinical presentation of IVH and PHH
      and provides a guideline for when and how to treat hydrocephalus in this
      population. Fibrinolytic therapy and neurodevelopmental outcomes are reviewed.

PMID- 11524296
TI  - Adult-onset hydrocephalus.
AB  - Adult-onset hydrocephalus can be acquired from other pathologies, congenital with
      a late onset, or idiopathic. Subarachnoid hemorrhage, normal-pressure
      hydrocephalus, tumors, and aqueductal stenosis are the most frequent causes, and
      clinical presentation may be acute or chronic. The pathophysiology of the more
      chronic form involves hypoxia and blood vessel changes. The treatment of adult
      hydrocephalus is dependent on its setting and may involve ventroposterior or
      ventroanterior shunting or endoscopic procedures.

PMID- 11524297
TI  - Normal-pressure hydrocephalus.
AB  - This article presents a brief history of normal-pressure hydrocephalus, its
      clinical presentation, and different theories on its pathophysiology. The
      different diagnostic tests, differential diagnosis, and its treatment are
      presented.

PMID- 11524298
TI  - Pseudotumor cerebri.
AB  - Pseudotumor cerebri is a disorder affecting mainly young, obese women. There is
      no known cause or single pathophysiologic mechanism to explain the disorder. The
      diagnosis is based on the triad of: (1) papilledema, (2) elevated intracranial
      pressure with a normal cerebrospinal fluid constituency, and (3) normal central
      nervous system imaging studies. Treatment involves various maneuvers to lower the
      intracranial pressure, including medicine and surgery.

PMID- 11524299
TI  - Frontal lobe changes in alcoholism: a review of the literature.
AB  - Alcohol can induce a wide spectrum of effects on the central nervous system.
      These effects can be recognized at the neurophysiological, morphological and
      neuropsychological levels. Several studies of the effect of alcohol on the
      frontal lobes were identified for review from MedLine, PsychLIT databases and by
      manual searching. In this review article, the different changes are examined in
      detail. Computed tomography studies have reported changes of frontal lobe in
      alcoholism, while magnetic resonance imaging studies supported these findings.
      Neurophysiological studies with positron emission tomography and single photon
      emission computed tomography have reported a decreased frontal lobe glucose
      utilization and reduced cerebral blood flow. There is also evidence from
      neuropsychological studies that there are specific deficits in alcoholism that
      suggest frontal lobe dysfunction. Considered together, these studies lend a
      strong credence to the concept of frontal lobe pathology in alcoholism. However,
      frontal lobe is not an isolated part of the brain and should be considered with
      its heavy connections to different cortical and subcortical areas of the brain.

PMID- 11524300
TI  - Ethanol modulates rat hepatic DNA repair functions.
AB  - To further explore how ethanol may act at the DNA level, studies have been made
      of DNA repair mechanisms in male Wistar rats given ethanol either as an acute
      intragastric dose (5 g/kg) or continuously in a liquid diet (5% w/v) to provide
      36% of the caloric intake. These treatments generate significant levels of free
      radicals with evidence of damage to DNA. The acute ethanol dose significantly
      inhibited O(6)-alkylguanine-DNA alkyltransferase (ATase) activity by 21-32%
      throughout the 24-h post-treatment period and this was confirmed by
      immunohistochemical detection of the ATase protein in hepatic nuclei. Twelve
      hours after the ethanol treatment, the activities of the DNA glycosylases,
      alkylpurine-DNA-N-glycosylase (APNG) and 8-oxoguanine-DNA glycosylase (OXOG
      glycosylase) were each increased by approximately 44%. In contrast, when given
      chronically via the liquid diet, ethanol initially had no effect on ATase
      activity, but after 4 weeks ATase activity was increased by 40%. Following
      ethanol withdrawal, ATase activity remained elevated for at least 12 h, but, by
      24 h, the activity had fallen to the uninduced control level. DNA glycosylase
      activities were again affected differently. After 1 week of dietary ethanol
      exposure, there was no effect on APNG activity but it was inhibited by 19% at 4
      weeks. OXOG glycosylase activity, on the other hand, was increased by 53% after 1
      week, but decreased by 40% after 4 weeks. Although some of these changes in DNA
      repair capacity were relatively small, over time, their potential impact on the
      repair of endogenous or exogenous alkylation and/or oxidation damage in DNA would
      be substantial. These studies indicate possible mechanisms for the co
      carcinogenic effects of ethanol.

PMID- 11524301
TI  - Cholinergic nerves mediate acetaldehyde action in the gastrointestinal tract.
AB  - The regulation mechanism of inhibition of intestinal ethanol absorption induced
      by high acetaldehyde (AcH) concentration in blood was investigated. We used
      atropine (AT), atropine methylbromide (ATMB), pirenzepine (PI), bethanechol (BE)
      and pilocarpine (PL) with or without cyanamide (CY; a potent inhibitor of
      aldehyde dehydrogenase, which induces high AcH concentration in blood). The K(a)
      (absorption rate constant) value after the CY-alone pretreatment was
      significantly lower than that in controls. In the high AcH-induced cases, the
      values of K(a) in AT and ATMB pretreatments were similar to controls, but the
      value of K(a) in PI pretreatment was lower than that in controls. The values of
      K(a) in the case of BE pretreatment with and without high AcH levels were lower
      than in controls. The K(a) value in the PL with CY was significantly lower than
      that with CY alone. However, its action was blocked by ATMB pretreatment. These
      results suggest that high blood AcH concentrations inhibit intestinal ethanol
      absorption through the peripheral cholinergic nerves via muscarinic receptors,
      except for the muscarinic M(1) receptor, compared to other subtypes of muscarinic
      receptors.

PMID- 11524302
TI  - Effects of acute and chronic ethanol administration on the response of mouse
      adipose tissue hormone-sensitive lipase to alpha(2)-adrenoceptor activation bu UK
      14304.
AB  - Untreated (control) obese CBA mice had lower hormone-sensitive lipase (HSL)
      activity and cAMP levels in brown adipose tissue than normal lean mice, but white
      adipose tissue HSL activity and cAMP were similar in obese and lean mice. In the
      obese mice, chronic ethanol treatment increased HSL activity and cAMP levels in
      both brown and white adipose tissue to above the levels in lean mice. In the lean
      mice, chronic ethanol only stimulated white adipose tissue. UK 14304 [5-bromo-6
      (2-imidazolin-2-ylamino)-quinoxaline: 2 mg/kg] inhibited HSL activity in both
      brown and white adipose tissues in lean mice, but a higher dose (3 mg/kg) was
      required to produce the same inhibition in obese mice. After chronic ethanol
      adipose tissues were more sensitive to UK 14304; only half the dose being
      required to produce the same level of lipase inhibition. We propose that,
      although chronic ethanol consumption increases cAMP levels in adipose tissue,
      particularly in obese mice, it also sensitizes the tissues to alpha(2)
      adrenoceptor stimulation. These effects may explain the increased sympathetic
      nervous system activity observed in alcohol withdrawal.

PMID- 11524303
TI  - Effect of ethanol exposure on Xenopus embryo lipid composition.
AB  - Exposure to ethanol is known to alter cell membranes both chemically and
      biophysically; these effects may be related to the development of tolerance and
      physical dependence. In the present study, the effects of various concentrations
      of ethanol (1-250 mM) on the lipid composition after the first 6 days of Xenopus
      embryo development were investigated, using an in vitro fertilization technique.
      Lipid analysis revealed: (1) a decrease of the cholesterol/phospholipid molar
      ratio mainly derived from a higher content of phospholipids; (2) an increase of
      phospholipid unsaturated fatty acids, especially C20:4 and C20:5, with ethanol
      concentration of 150-250 mM; (3) a decrease of lipid-bound sialic acid with
      ethanol concentrations of > or =5 mM. These results underline that
      sialoglycoconjugates are a more sensitive target of alcohol in comparison with
      other lipid components. The cultured embryo method certainly represents a useful
      model for investigation of the direct effects of ethanol on lipid metabolism,
      excluding maternal interference which can lead to misinterpretation of data.

PMID- 11524304
TI  - Alcoholic polyneuropathy: a clinical and epidemiological study.
AB  - In the present study, we investigated the frequency of polyneuropathy in a sample
      of 296 alcoholics who were admitted to the 'S. Maugeri' Medical Centre for
      detoxification from October 1997 to November 1999. Results revealed a high
      frequency of polyneuropathy in the sample under study. The disorder was often
      clinically asymptomatic and demonstrable only on electroneurographic
      investigation. Significant correlations were found between polyneuropathy, the
      duration of alcoholism, the type of alcoholic beverage consumed (wine) and the
      presence of liver disease and macrocytosis.

PMID- 11524305
TI  - The gin epidemic: much ado about what?
AB  - While there is no doubt that the era of the 'gin epidemic' was associated with
      poverty and social unrest, the surge in gin drinking was localized to London and
      was a concomitant, not the cause, of these problems. The two main underlying
      social problems were widespread overcrowding and poverty. The former was related
      to an unprecedented migration of people from the country to London. The latter
      stemmed from an economic ideology called 'poverty theory', whose basic premise
      was that, by keeping the 'inferior order' in poverty, English goods would be
      competitive and would remain that way since workers would be completely dependent
      on their employers. Widespread overcrowding and poverty led to societal unrest
      which manifested itself in increased drunkenness when cheap gin became available
      after Parliament did away with former distilling monopolies that had kept prices
      high. Reformers ignored the social causes of this unrest and, instead, focused on
      gin drinking by the poor which they feared was endangering England's wealth and
      security by enfeebling its labour force, and reducing its manpower by decreasing
      its population. Part of this hostility was also related to gin itself. While
      drunkenness was often spoken of affectionately when it was induced by beer,
      England's national drink, gin was considered a foreign drink, and therefore less
      acceptable. These concerns were voiced less often after the passage of the
      Tippling Act of 1751, which resulted in an increase in gin prices and decreased
      consumption. However, the second half of the century was also a period in which
      England's military victory over the French gave it new wealth and power, which
      dispelled upper-class fears about an enfeebled and dissolute working class. It
      was also an era when new public health measures, such as mass inoculation against
      smallpox, and a decrease in the marrying age, led to a population increase that
      dispelled reformist fears about manpower shortages. The conclusion is that, while
      the lower cost of gin sparked the 'gin epidemic', the social unrest associated
      with this unprecedented surge in gin consumption was exacerbated, rather than
      caused, by the increase in drinking.

PMID- 11524306
TI  - Study of Axis-Shield new %CDT immunoassay for quantification of carbohydrate
      deficient transferrin (CDT) in serum.
AB  - Carbohydrate-deficient transferrin (CDT) in serum has emerged as a useful
      biochemical marker for identifying current alcohol misuse and monitoring
      abstinence. This study evaluated the performance of Axis-Shield new %CDT
      turbidimetric immunoassay (TIA; microtitre and Cobas Mira applications).
      Comparison was made with the previous Axis %CDT-TIA immunoassay (reference value
      <5.5%) and %CDT with the high-performance liquid chromatography (HPLC) technique
      (reference value <1.2%). The new %CDT assay measures primarily the asialo,
      monosialo and disialo transferrin isoforms, and the result is expressed as the
      amount relative to total transferrin. The analytical precision (coefficient of
      variation: CV) of the %CDT assay ranged between 3.1 and 8.5% for kit controls and
      serum samples. The %CDT values in serum from healthy social drinkers [i.e.
      Alcohol Use Disorders Identification Test (AUDIT) score 1-7 for men, and 1-5 for
      women] were 2.07 +/- 0.37% (mean +/- SD, range 1.4-3.3%, n = 100) and this was
      not significantly different from healthy non-drinkers (1.88 +/- 0.43%, 1.3-2.9%,
      n = 14), whereas abstinent alcohol patients showed slightly higher values (2.26
      +/- 0.41, 1.7-3.4, n = 25). In chronic heavy drinkers (mean daily intake 225 +/-
      137 g ethanol according to self-report), the %CDT values were markedly increased
      (6.33 +/- 4.01%, 1.2-18.0%, n = 107). There was no significant difference in %CDT
      values between male and female social drinkers. The reference value of the new
      %CDT assay to be used in clinical practice was tentatively set at <3.0%, which is
      slightly higher than that obtained by receiver operating characteristics (ROC)
      curve analysis (<2.8%) and that proposed by the manufacturer in the Instruction
      Manual (<2.6%). The %CDT assay showed good overall correlation with %CDT-TIA (r =
      0.986, P < 0.0001) and %CDT-HPLC (r = 0.978, P < 0.0001). The specificity of the
      %CDT assay in healthy social drinkers was 98% (%CDT-TIA 100%, %CDT-HPLC 99%) and
      the sensitivity for any drinking during last week in the alcohol patients was 75%
      (%CDT-TIA 71%, %CDT-HPLC 80%). The new Axis-Shield %CDT assay can be recommended
      for routine use. However, whenever a positive immunoassay test result could lead
      to serious consequences for the individual, it is recommended to confirm the CDT
      result by the HPLC technique.

PMID- 11524307
TI  - Acamprosate during and after acute alcohol withdrawal: a double-blind placebo
      controlled study in Spain.
AB  - To test acamprosate's role as an aid in preventing relapse after detoxification,
      296 alcohol-dependent patients entered a prospective, multicentre, randomized,
      double-blind, parallel comparison of acamprosate treatment consisting of two 333
      mg tablets given three times daily for 180 days with matching placebo treatment.
      Unlike previous studies, acamprosate was prescribed from the start of alcohol
      withdrawal, rather than after the detoxification process. During the treatment
      period, 110 patients dropped out. The two treatment groups were balanced with
      regard to baseline values and reasons for discontinuation. There was no
      difference between the groups in the severity of withdrawal symptoms as measured
      by the CIWA-Ar (Clinical Institute Withdrawal Assessment for Alcohol scale).
      Acamprosate given during withdrawal did not cause unwanted effects. The
      cumulative abstinence duration (CAD, main end-point) was 19 days longer in the
      acamprosate treatment group than the placebo treatment group (analysis of
      variance on ranks, P = 0.0006) and the stable recovery duration, defined as the
      number of abstinent days between the last relapse into any drinking and the end
      of the trial, was 16 days longer in the acamprosate treatment group (P = 0.021).
      Continuous abstinence, estimated by survival analysis on time to first relapse,
      was achieved by 35% of acamprosate-treated patients and 26% of placebo-treated
      patients (log rank P = 0.068). The geometric mean of the ratio final/baseline
      values for serum carbohydrate-deficient transferrin was 0.802 (placebo) and 0.733
      (acamprosate) (P = 0.059). The geometric mean of the ratio final/baseline values
      for serum gamma-glutamyltransferase was 0.496 (placebo) and 0.415 (acamprosate)
      (P = 0.024) which corroborated the greater abstinence reported by the acamprosate
      group.

PMID- 11524308
TI  - Naltrexone versus acamprosate: one year follow-up of alcohol dependence
      treatment.
AB  - Naltrexone and acamprosate reduce relapse in alcohol dependence. They have not
      yet been compared in a published trial. The aim of this study was to compare the
      efficacy of these compounds in conditions similar to those in routine clinical
      practice. Random allocation to a year of treatment with naltrexone (50 mg/day) or
      acamprosate (1665-1998 mg/day) was made in 157 recently detoxified alcohol
      dependent men with moderate dependence (evaluated using the Addictions Severity
      Index and Severity of Alcohol Dependence Scale). All were patients whom a member
      of the family would accompany regularly to appointments. Alcohol consumption,
      craving and adverse events were recorded weekly for the first 3 months, and then
      bi-weekly, by the treating psychiatrist who was not blinded. At 3-monthly
      intervals, investigators who were blinded to the treatment documented patients'
      alcohol consumption based on patients' accounts, information given by the
      psychiatrists when necessary, and reports from patients' families. Serum gamma
      glutamyltransferase (GGT) was also measured. Efforts were made to sustain the
      blindness of the investigators. The same investigator did not assess the same
      patient twice. The integrity of the blindness was not checked. There was no
      difference between treatments in mean time to first drink (naltrexone 44 days,
      acamprosate 39 days) but the time to first relapse (five or more drinks in a day)
      was 63 days (naltrexone) versus 42 days (acamprosate) (P = 0.02). At the end of 1
      year, 41% receiving naltrexone and 17% receiving acamprosate had not relapsed (P
      = 0.0009). The cumulative number of days of abstinence was significantly greater,
      and the number of drinks consumed at one time and severity of craving were
      significantly less, in the naltrexone group compared to the acamprosate group, as
      was the percentage of heavy drinking days (P = 0.038). More patients in the
      acamprosate than the naltrexone group were commenced on disulfiram during the
      study. Naltrexone patients attended significantly more group therapy sessions,
      though this could not explain their better outcome. There were non-significant
      trends for the naltrexone group to comply better with medication, to stay in the
      study longer, and to show greater improvement over baseline in serum GGT.

PMID- 11524309
TI  - A double-blind randomized placebo-controlled trial of lofexidine in alcohol
      withdrawal: lofexidine is not a useful adjunct to chlordiazepoxide.
AB  - Lofexidine is an alpha-adrenoceptor agonist which has proved useful in opiate
      withdrawal and which, through its attenuation of noradrenergic activity, might be
      a valuable adjunct in the management of alcohol withdrawal. The objective of this
      study was to compare the clinical effectiveness and patient retention with
      adjunctive lofexidine versus placebo in the treatment of alcohol withdrawal under
      chlordiazepoxide cover. This was done in a prospective double-blind randomized
      placebo-controlled trial with 72 alcohol-dependent adults referred and admitted
      for in-patient alcohol detoxification. The adjunctive lofexidine group
      experienced significantly more severe withdrawal symptoms, greater hypotensive
      problems, more adverse effects, and no better rates of retention in treatment.
      Lofexidine provides no discernible benefit as an adjunctive medication (to
      chlordiazepoxide) in alcohol detoxification and, on the basis of our study,
      appears to be contra-indicated.

PMID- 11524310
TI  - At which drinking level to advise a patient? General practitioners' views.
AB  - This study examined the views of 64 general practitioners (GPs) on how much a
      patient has to drink to be advised by them and compared the results to the
      recommended Finnish threshold values of heavy drinking. The levels stated by GPs
      were not too high to prevent early-phase intervention in heavy drinking; rather,
      they were so low that numerous moderate drinkers were also included. The mean
      (SD) level was 15.5 (6.5) drinks for male and 11.0 (4.6) drinks for female
      patients per week. These are about two-thirds of the Finnish threshold values of
      heavy drinking. Attempting to advise such high proportions of patients, including
      both heavy and moderate drinkers, might mean a discouraging burden for GPs.
      However, there may be a discrepancy between GPs' statements about when to advise
      and when they actually do so.

PMID- 11524312
TI  - Epidural anesthesia and analgesia for coronary artery bypass graft surgery: still
      forbidden territory?

PMID- 11524313
TI  - Pain medicine and anesthesiologists: a new section of the journal.

PMID- 11524314
TI  - A prospective randomized study of the potential benefits of thoracic epidural
      anesthesia and analgesia in patients undergoing coronary artery bypass grafting.
AB  - We performed an open, prospective, randomized, controlled study of the incidence
      of major organ complications in 420 patients undergoing routine coronary artery
      bypass graft surgery with or without thoracic epidural anesthesia and analgesia
      (TEA). All patients received a standardized general anesthetic. Group TEA
      received TEA for 96 h. Group GA (general anesthesia) received narcotic analgesia
      for 72 h. Both groups received supplementary oral analgesia. Twelve patients were
      excluded-eight in Group TEA and four in Group GA-because of incomplete data
      collection. New supraventricular arrhythmias occurred in 21 of 206 patients
      (10.2%) in Group TEA compared with 45 of 202 patients (22.3%) in Group GA (P =
      0.0012). Pulmonary function (maximal inspiratory lung volume) was better in Group
      TEA in a subset of 93 patients (P < 0.0001). Extubation was achieved earlier (P <
      0.0001) and with significantly fewer lower respiratory tract infections in Group
      TEA (TEA = 31 of 206, GA = 59 of 202; P = 0.0007). There were significantly fewer
      patients with acute confusion (GA = 11 of 202, TEA = 3 of 206; P = 0.031) and
      acute renal failure (GA = 14 of 202, TEA = 4 of 206; P = 0.016) in the TEA group.
      The incidence of stroke was insignificantly less in the TEA group (GA = 6 of 202,
      TEA = 2 of 206; P = 0.17). There were no neurologic complications associated with
      the use of TEA. We conclude that continuous TEA significantly improves the
      quality of recovery after coronary artery bypass graft surgery compared with
      conventional narcotic analgesia.

PMID- 11524315
TI  - Intraoperative plateletpheresis and autologous platelet gel do not reduce chest
      tube drainage or allogeneic blood transfusion after reoperative coronary artery
      bypass graft.
AB  - Platelet-rich plasma (PRP) is postulated to decrease postoperative mediastinal
      chest tube drainage (MCTD) and allogeneic blood transfusions (ABT) after surgery
      with cardiopulmonary bypass. However, recent metaanalysis of the literature
      reveals that few good quality (therapeutic yield) trials that show a benefit have
      been published. The potential hemodynamic instability caused by plateletpheresis
      has not been emphasized. We studied the effect of plateletpheresis on MCTD, ABT,
      and hemodynamic stability in reoperative coronary artery bypass graft patients, a
      group perceived to be at high risk for ABT. Ninety patients were randomly
      assigned to Pheresis or Control groups. epsilon-Aminocaproic acid was given to
      all patients. Hemodynamic instability was assessed by degree of volume and
      inotrope resuscitation required. Part of the sequestered platelet volume was used
      to make autologous platelet gel, which was applied as a wound sealant. Mean
      pheresis yield was 30% +/- 7% of the circulating platelet mass or 6.4 +/- 2.2
      allogeneic platelet unit equivalents. Total MCTD did not differ between the
      groups. There were no differences in mean packed red blood cell, platelet, and
      plasma transfusion rates. Overall, 52% of the Pheresis group received ABT, versus
      55% of the Control group. Fifty-three percent of the Pheresis group patients
      exhibited significant hemodynamic instability, versus 27% of the Control group (P
      < 0.05). This study was unable to show any reduction in MCTD or ABT, although the
      plateletpheresis technique may offset platelet dysfunction caused by aspirin or
      increased blood exposure to nonbiologic surfaces, or it may compensate for lack
      of antifibrinolytic use. The significantly increased incidence of hemodynamic
      instability in the Pheresis group means that the risk/benefit ratio must be
      determined for individual cardiac surgical units.

PMID- 11524316
TI  - The in vitro effects of remifentanil, sufentanil, fentanyl, and alfentanil on
      isolated human right atria.
AB  - Because some clinical studies have suggested that opioids used in anesthesia may
      have different deleterious hemodynamic effects, we compared the direct myocardial
      effects of cumulative concentrations of remifentanil, sufentanil, fentanyl, and
      alfentanil on inotropic and lusitropic variables of isolated human myocardium in
      vitro. Human right atrial trabeculae, obtained from patients scheduled for
      coronary bypass surgery or aortic valve replacement, were suspended vertically in
      an oxygenated (95% oxygen/5% CO(2)) Tyrode's modified solution ([Ca(2+)](o) = 2.0
      mM, 37 degrees C, pH 7.40, stimulation frequency 1 Hz). The effects of cumulative
      concentrations (10(-11), 10(-10), 10(-9), 10(-8), 10(-7), and 10(-6) M) of
      remifentanil (n = 8), sufentanil (n = 8), fentanyl (n = 8), and alfentanil (n =
      8) on inotropic and lusitropic variables of isometric twitches were measured.
      Remifentanil, sufentanil, and fentanyl did not modify active isometric force and
      peak of the positive force derivative as compared with the Control group.
      Alfentanil induced a dose-dependent decrease in active isometric force and peak
      of the positive force derivative. This effect was abolished in the presence of
      [Ca(2+)](o) = 4.0 mM. None of these opioids altered lusitropic variables.

PMID- 11524317
TI  - The effects of propofol on the contractility of failing and nonfailing human
      heart muscles.
AB  - We determined the direct effects of propofol on the contractility of human
      nonfailing atrial and failing atrial and ventricular muscles. Atrial and
      ventricular trabecular muscles were obtained from the failing human hearts of
      transplant patients or from nonfailing hearts of patients undergoing coronary
      artery bypass surgery. Isometric contraction variables were recorded before and
      after propofol was added to the bath in concentrations between 0.056 and 560
      microM. The effects of propofol were compared with its commercial vehicle
      intralipid. To test beta-adrenergic effects in the presence of propofol, 1 microM
      isoproterenol was added at the end of each experiment. To determine the cellular
      mechanisms responsible for the actions of propofol, we examined its effects on
      actomyosin ATPase activity and sarcoplasmic reticulum (SR) Ca(2+) uptake in
      nonfailing atrial tissues. Propofol caused a concentration-dependent decrease in
      maximal developed tension in all muscles, which became significant (P < 0.05) at
      concentrations exceeding the clinical range (> or =56 microM). Isoproterenol
      restored contractility to the level achieved before exposure to propofol (P >
      0.05 compared with baseline). Failing ventricular muscle exposed to propofol
      exhibited somewhat diminished ability to recover contractility in response to
      isoproterenol (P < 0.05 versus failing muscle exposed to intralipid only).
      Propofol induced a concentration-dependent decrease in the uptake of Ca(2+) into
      SR vesicles. At the same time, in the presence of 56 microM propofol, the Ca(2+)
      activated actomyosin ATPase activity was shifted leftward, demonstrating an
      increase in myofilament sensitivity to Ca(2+). We conclude that propofol exerts a
      direct negative inotropic effect in nonfailing and failing human myocardium, but
      only at concentrations larger than typical clinical concentrations. Negative
      inotropic effects are reversible with beta-adrenergic stimulation. The negative
      inotropic effect of propofol is at least partially mediated by decreased Ca(2+)
      uptake into the SR; however, the net effect of propofol on contractility is
      insignificant at clinical concentrations because of a simultaneous increase in
      the sensitivity of the myofilaments to activator Ca(2+).

PMID- 11524318
TI  - A comparison of sevoflurane, target-controlled infusion propofol, and
      propofol/isoflurane anesthesia in patients undergoing carotid surgery: a quality
      of anesthesia and recovery profile.
AB  - In a prospective randomized study in patients undergoing carotid endarterectomy,
      we compared the hemodynamic effects, the quality of induction, and the quality of
      recovery from a hypnotic drug for the induction of anesthesia with sevoflurane, a
      target-controlled infusion (TCI) of propofol, or propofol 1.5 microg/kg followed
      by isoflurane. All patients were premedicated with midazolam and received
      sufentanil 0.4 microg/kg at induction. The induction of anesthesia was associated
      with a decrease in arterial blood pressure in all groups, but this was least
      pronounced in the Sevoflurane group. There were similar a number of episodes of
      hypotension, hypertension, and tachycardia among groups, but the incidence of
      bradycardia was less in the TCI group (P < 0.05) compared with the other groups.
      The duration of episodes of hypotension was shorter (P < 0.05) in the TCI
      Propofol group (1.9 +/- 2.3 min) compared with the Sevoflurane group (4.7 +/- 3.6
      min). The duration of episodes of bradycardia was significantly lower (P < 0.05)
      in the TCI Propofol group (0.1 +/- 0.5 min) in comparison with the Propofol Bolus
      group (2.5 +/- 3.9 min). Similar doses of vasoactive drugs were used in all
      groups. The induction of anesthesia with sevoflurane was associated with inferior
      conditions for intubation in comparison with both Propofol groups, although the
      time to intubation was faster in the Sevoflurane group (P < 0.05). The recovery
      characteristics were similar in the three groups.

PMID- 11524319
TI  - Are leukocytes in salvaged washed autologous blood harmful for the recipient? The
      results of a pilot study.
AB  - To explore whether polymorphonuclear leukocytes (PMNL) are activated to the
      priming threshold through intraoperative blood salvage, and are thus able to
      induce endothelial damage, we investigated chemotactic response (n = 20) and
      respiratory burst (RB; n = 20) of PMNL without (basal respiratory burst, bPMNL
      RB) and after in vitro stimulation with formyl-Met-Leu-Phe (fMLP-RB) and phorbol
      myristate acetate (PMA-RB). Blood was processed with a continuous autotransfusion
      device (CATS). Heparin (Heparin group) and sodium citrate (Citrate group) were
      used alternately as an anticoagulant for each half of the chemotaxis and RB
      studies. Comparison of measurements from the processed autologous erythrocyte
      concentrates (paEC) to pre- and intraoperative arterial blood samples showed no
      statistically significant difference for any test of PMNL functional responses in
      an orthopedic patient population. Analysis of intraindividual changes
      demonstrated a significantly increased bPMNL-RB (both groups, P = 0.0032; Heparin
      group, P = 0.0098), fMLP-RB (both groups, P = 0.0484; Citrate group, P = 0.0371),
      and PMA-RB (Citrate group, P = 0.002) in the paEC compared with intraoperative
      arterial samples, whereas the chemotactic response did not change. Nevertheless,
      median values of all RB measurements in the paEC were within the range of pre-
      and intraoperative values, indicating that PMNLs contained in the paEC are
      neither impaired nor activated to the priming threshold. The results confirm the
      clinical experience that intraoperative blood salvage is safe to use during major
      orthopedic surgery and questions the beneficial effect of special leukocyte
      removing filters.

PMID- 11524320
TI  - The effect of perioperative aspirin therapy in peripheral vascular surgery: a
      decision analysis.
AB  - Patients who undergo infrainguinal revascularization surgery are at increased
      risk for perioperative thrombotic complications. Aspirin decreases thrombotic
      events in the nonoperative setting; however, aspirin is often discontinued to
      avoid perioperative hemorrhagic complications. We used a decision analysis to
      determine whether aspirin should be discontinued before infrainguinal
      revascularization surgery. Two strategies were compared: aspirin cessation 2 wk
      before surgery and aspirin continuation throughout the perioperative period.
      Clinical events examined included myocardial infarction, thrombotic
      cerebrovascular accident, hemorrhagic cerebrovascular accident, gastrointestinal
      hemorrhage, and incisional hemorrhagic complications. Event rates and effect of
      aspirin were obtained by using MEDLINE. The outcomes were perioperative
      mortality, life expectancy, and quality-adjusted life expectancy. According to
      the model, continued aspirin use decreased perioperative mortality rates from
      2.78% to 2.05%. Continued aspirin use increased life expectancy from 14.83 to
      14.89 yr and increased quality-adjusted life expectancy from 14.72 to 14.79 yr.
      Aspirin increased the number of hemorrhagic complications by 2.46%, primarily
      because of an increased incidence of non-life-threatening complications.

PMID- 11524321
TI  - Resensitization of blood pressure response to mu-opioid peptide agonists after
      acute desensitization.
AB  - IV administration of mu-opioid peptide agonists (DAMGO, DALDA, and [Dmt(1)]DALDA)
      results in a transient, naloxone-sensitive, increase in blood pressure in awake
      sheep. Despite significant differences in pharmacokinetics, these blood pressure
      responses all last < 15 min. The lack of correlation between half-life and
      duration of action suggested rapid desensitization. When a second dose of the
      same agonist was repeated 30 min later, the response was completely abolished. An
      increase in blood pressure and rapid desensitization was also observed with the
      kappa-opioid agonist (U50488H), whereas delta-agonists (DPDPE and DELT) had no
      effect on blood pressure. The response to DAMGO was abolished after prior
      exposure to DAMGO or DALDA, but there was no evidence of cross-desensitization
      between mu and delta, or mu and kappa, opioid agonists. Full resensitization of
      the blood pressure response occurred by 4 h for DAMGO (t(1/2) = 15 min) and by 48
      h for [Dmt(1)]DALDA (t(1/2) = 1.8 h). These data support our hypothesis that the
      transient nature of the blood pressure response to mu-opioid agonists is caused
      by rapid desensitization and suggest that the rate of resensitization is
      dependent on the pharmacokinetics of the agonist.

PMID- 11524322
TI  - Acute renal failure after radiofrequency liver ablation of metastatic carcinoid
      tumor.
AB  - IMPLICATIONS: We report a case of prolonged radiofrequency liver ablation for
      metastatic carcinoid tumor complicated by hemolysis, rhabdomyolysis, and
      transient acute renal failure. Brief radiofrequency liver ablation procedures or
      those for a small number of tumor sites are not associated with these
      complications.

PMID- 11524323
TI  - EMLA versus nitrous oxide for venous cannulation in children.
AB  - We compared EMLA cream with nitrous oxide (N(2)O) for providing pain relief
      during venous cannulation in children. In a prospective, double-blinded,
      randomized study, 40 children, 6-11 yr, ASA status I or II, undergoing scheduled
      surgery received either EMLA cream and inhaled air and oxygen (Group EMLA) or a
      placebo cream and inhaled 70% N(2)O in oxygen (Group N(2)O) before venous
      cannulation. Pain was evaluated with a visual analog scale and the Objective Pain
      Scale. The ease of venous cannulation and the observer's assessment of its
      efficacy for preventing pain were assessed. Heart rate, blood pressure,
      respiratory rate, and oxygen saturation were compared before and after venous
      cannulation. Visual analog scale scores (4.4 +/- 7.5 vs 3.9 +/- 9.3 mm, P =
      0.85), Objective Pain Scale scores (median 0 [0-6] vs 0 [0-1], P = 0.61),
      efficacy (median 0 [0-1] vs 0 [0-1], P = 0.59), and ease of venous cannulation (0
      [0-2] vs 0 [0-1], P = 0.84) were not different between EMLA and N(2)O groups,
      respectively. There was no statistical difference between the groups for the
      physiologic variables. Minor side effects were significantly more common in the
      N(2)O group (11 of 20) than in the EMLA group (7 of 20) (P = 0.0248). We conclude
      that both techniques provided adequate pain relief during venous cannulation, as
      demonstrated by the low pain scores.

PMID- 11524324
TI  - The assessment of the proximal left pulmonary artery by transesophageal
      echocardiography and computed tomography in neonates and infants: a case series.
AB  - IMPLICATIONS: Transesophageal echocardiography (TEE) is often used during
      surgical repair of congenital heart disease. In our case series of 256 newborns
      and infants, we found that a left paracarinal view of TEE could visualize the
      proximal left pulmonary artery, a frequent blind spot for TEE, in most patients,
      except in a few cases with anatomic variations of the esophagus in the right
      lateral to the vertebra.

PMID- 11524325
TI  - The effect of preoperative epidural morphine on postoperative analgesia in
      children.
AB  - IMPLICATIONS: We examined the effects of preoperative epidural morphine
      associated with general anesthesia on postoperative morphine requirements. Twenty
      one children older than 6 yr scheduled for major surgery were randomly assigned
      to two groups, a control group and an epidural group that received a single
      epidural morphine injection.

PMID- 11524326
TI  - Interscalene brachial plexus block with continuous intraarticular infusion of
      ropivacaine.
AB  - Providing intraarticular analgesia with a continuous infusion of local anesthetic
      via a disposable infusion pump has gained popularity. Despite the prevalence of
      this technique, data comparing this method of analgesia to conventional regional
      anesthesia are not available. We present a prospective study that compared a
      single-dose interscalene block with a single-dose interscalene block plus
      continuous intraarticular infusion of local anesthetic. Forty patients scheduled
      for shoulder arthroscopy were entered in this prospective, double-blinded study.
      All patients received an interscalene brachial plexus block as their primary
      anesthetic. Patients were randomly assigned to 1 of 2 groups: 1. interscalene
      block with 1.5% mepivacaine (40 mL) followed by a postoperative intraarticular
      infusion of 0.5% ropivacaine at 2 mL/h, or 2. interscalene block with 0.5%
      ropivacaine (40 mL) followed by a postoperative intraarticular infusion of 0.9%
      saline (placebo) at 2 mL/h. Postoperative infusions were maintained for 48 h.
      Visual analog scale pain scores and postoperative oxycodone consumption were
      measured for 48 h. Visual analog scale scores at rest and with ambulation in the
      Mepivacaine/Intraarticular Ropivacaine group were reduced when compared with the
      Ropivacaine/Saline group (rest: P = 0.003, ambulation: P = 0.006). Oxycodone
      consumption was also decreased (28 +/- 21 mg vs 44 +/- 28 mg, P = 0.046),
      respectively. We conclude that a brachial plexus block with 1.5% mepivacaine and
      a continuous intraarticular infusion of 0.5% ropivacaine at 2 mL/h provides
      improved analgesia for minor surgery at 24 and 48 h versus a single-injection
      interscalene block with 0.5% ropivacaine.

PMID- 11524327
TI  - Intraoperative small-dose ketamine enhances analgesia after outpatient knee
      arthroscopy.
AB  - Ketamine may prevent postoperative hyperalgesia. In patients undergoing
      arthroscopic meniscectomy using general anesthesia, we tested whether a single
      intraoperative dose of ketamine enhanced postoperative analgesia and improved
      functional outcome compared with a typical multimodal analgesic regimen. After
      the induction of anesthesia, 50 patients were randomly assigned to ketamine (0.15
      mg/kg IV just after the induction of anesthesia) or a vehicle placebo.
      Standardized general anesthesia included propofol, alfentanil, and nitrous oxide.
      Bupivacaine (0.5%) and morphine (5 mg) were given intraarticularly at the end of
      surgery. Postoperative analgesia was initially provided with morphine and
      subsequently with naproxen sodium (550 mg orally twice daily) and Di-Antalvic
      (400 mg acetaminophen and 30 mg dextropropoxyphene) as needed. Pain scores,
      analgesic requirements, side effects, and ability to walk were assessed in the
      ambulatory unit and at home for three postoperative days. Times to awakening and
      to discharge were similar in the two groups. However, the Ketamine group had
      significantly less postoperative pain at rest and during mobilization on Days 0,
      1, and 2. Furthermore, they consumed significantly fewer Di-Antalvic tablets than
      the control group (13 [7-17] vs 27 [16-32], median [25%-75% interquartile
      range]). Patients given ketamine were also able to walk for longer periods of
      time on the first postoperative day. In conclusion, adding small-dose ketamine to
      a multimodal analgesic regimen improved postoperative analgesia and functional
      outcome after outpatient knee arthroscopy.

PMID- 11524328
TI  - The effect of bispectral index monitoring on end-tidal gas concentration and
      recovery duration after outpatient anesthesia.
AB  - We performed this study to determine whether instituting monitoring of bispectral
      index (BIS) throughout an entire operating room would affect end-tidal gas
      concentration (as a surrogate for anesthetic use) or speed of recovery after
      outpatient surgery. Primary caregivers (n = 69) were randomly assigned to a BIS
      or non-BIS Control group with cross-over at 1-mo intervals for 7 mo. Data were
      obtained in all outpatients except for those having head-and-neck surgery. Mean
      end-tidal gas concentration and total recovery duration were compared by unpaired
      t-test. Overall, 469 patients (80%) received propofol for induction and
      sevoflurane for maintenance. This homogeneous group was selected for statistical
      analysis. Mean end-tidal sevoflurane concentration was 13% less in the BIS group
      (BIS, 1.23%; Control, 1.41%; P < 0.0001); differences were most evident when
      anesthesia was administered by first-year trainees. Mean BIS values were 47 in
      the BIS-Monitored group. Total recovery was 19 min less with BIS monitoring in
      men (BIS group, 147 min; Controls, 166 min; P = 0.035), but not different in
      women. We conclude that routine application of BIS monitoring is associated with
      a modest reduction in end-tidal sevoflurane concentration. In men, this may
      correlate with a similar reduction (11%) in recovery duration.

PMID- 11524330
TI  - The inhibitory effect of bupivacaine on prostaglandin E(2) (EP(1)) receptor
      functioning: mechanism of action.
AB  - Prostaglandin E(2) receptors, subtype EP(1) (PGE(2)EP(1)) have been linked to
      several physiologic responses, such as fever, inflammation, and mechanical
      hyperalgesia. Local anesthetics modulate these responses, which may be due to
      direct interaction of local anesthetics with PGE(2)EP(1) receptor signaling. We
      sought to characterize the local anesthetic effects on PGE(2)EP(1) signaling and
      elucidate mechanisms of anesthetic action. In Xenopus laevis oocytes, recombinant
      expressed PGE(2)EP(1) receptors were functional (half maximal effect
      concentration, 2.09 +/- 0.98 x 10(-6) M). Bupivacaine, after incubation for 10
      min, inhibited concentration-dependent PGE(2)EP(1) receptor functioning (half
      maximal inhibitory effect concentration, 3.06 +/- 1.26 x 10(-6) M). Prolonged
      incubation in bupivacaine (24 h) inhibited PGE(2)-induced calcium-dependent
      chloride currents (I(Cl(Ca))) even more. Intracellular pathways were not
      significantly inhibited after 10 min of incubation in bupivacaine. But I(Cl(Ca))
      activated by intracellular injection of GTPgammaS (a nonhydrolyzable guanosine
      triphosphate [GTP] analog that activates G proteins, irreversible because it
      cannot be dephosphorylated by the intrinsic GTPase activity of the alpha subunit
      of the G protein) was reduced after 24 h of incubation in bupivacaine, indicating
      a G protein-dependent effect. However, inositol 1,4,5-trisphosphate- and CaCl(2)-
      induced I(Cl(Ca)) were unaffected by bupivacaine at any time points tested.
      Therefore, bupivacaine's effect is at phospholipase C or at the G protein or the
      PGE(2)EP(1) receptor. All inhibitory effects were reversible. We conclude that
      bupivacaine inhibited PGE(2)EP(1) receptor signaling at clinically relevant
      concentrations. These effects could, at least in part, explain how local
      anesthetics affect physiologic responses such as fever, inflammation, and
      hyperalgesia during the perioperative period.

PMID- 11524329
TI  - Neither nalbuphine nor atropine possess special antishivering activity.
AB  - The special antishivering action of meperidine may be mediated by its kappa or
      anticholinergic actions. We therefore tested the hypotheses that nalbuphine or
      atropine decreases the shivering threshold more than the vasoconstriction
      threshold. Eight volunteers were each evaluated on four separate study days: 1)
      control (no drug), 2) small-dose nalbuphine (0.2 microg/mL), 3) large-dose
      nalbuphine (0.4 microg/mL), and 4) atropine (1-mg bolus and 0.5 mg/h). Body
      temperature was increased until the patient sweated and then decreased until the
      patient shivered. Nalbuphine produced concentration-dependent decreases (mean +/-
      SD) in the sweating (-2.5 +/- 1.7 degrees C. microg(-1). mL; r(2) = 0.75 +/-
      0.25), vasoconstriction (-2.6 +/- 1.7 degrees C. microg(-1). mL; r(2) = 0.75 +/-
      0.25), and shivering (-2.8 +/- 1.7 degrees C. microg(-1). mL; r(2) = 0.79 +/-
      0.23) thresholds. Atropine significantly increased the thresholds for sweating
      (1.0 degrees C +/- 0.4 degrees C), vasoconstriction (0.9 degrees C +/- 0.3
      degrees C), and shivering (0.7 degrees C +/- 0.3 degrees C). Nalbuphine reduced
      the vasoconstriction and shivering thresholds comparably. This differs markedly
      from meperidine, which impairs shivering twice as much as vasoconstriction.
      Atropine increased all thresholds and would thus be expected to facilitate
      shivering. Our results thus fail to support the theory that activation of kappa
      opioid or central anticholinergic receptors contribute to meperidine's special
      antishivering action.

PMID- 11524331
TI  - Xenon does not affect human platelet function in vitro.
AB  - We sought to determine whether xenon affects platelet glycoprotein expression and
      platelet-related hemostasis in vitro at a clinically relevant concentration.
      Human whole blood was stimulated with either adenosine diphosphate or the
      thrombin receptor agonist peptide (TRAP)-6 after incubation with 65% xenon.
      Halothane at 2 minimum alveolar anesthetic concentration was used as a positive
      control. Platelet function and activation were evaluated with two-color flow
      cytometry. The expression of the platelet glycoproteins GPIIb/IIIa, GPIb, and P
      selectin were detected with fluorochrome-conjugated monoclonal antibodies. In
      vitro measurement of platelet-related hemostasis under conditions of high shear
      stress was performed in citrated whole blood with a platelet function analyzer
      (PFA-100((R))) by using collagen/epinephrine and collagen/adenosine diphosphate
      cartridges. Xenon did not affect basal or agonist-induced expression of platelet
      membrane glycoproteins, activation-dependent conformational changes of the
      GPIIb/IIIa receptor, expression of P selectin, or PFA closure times. In contrast,
      halothane reduced TRAP-6-induced activation of the GPIIb/IIIa complex.
      Furthermore, collagen/epinephrine-induced PFA closure time was significantly
      prolonged. These results demonstrate that xenon does not affect the unstimulated
      or agonist-induced platelet glycoprotein expression, activation of GPIIb/IIIa, or
      platelet-related hemostasis.

PMID- 11524332
TI  - A comparison of atenolol, labetalol, esmolol, and landiolol for altering human
      neutrophil functions.
AB  - IMPLICATIONS: Neutrophils play a pivotal role in the antibacterial host defense
      system. Atenolol, labetalol, esmolol, and landiolol at clinically relevant
      concentrations failed to change neutrophil functions. Our findings indicate that
      we may be able to use these beta-antagonists without great caution in clinical
      settings.

PMID- 11524333
TI  - Propofol-induced bronchoconstriction: two case reports.
AB  - IMPLICATIONS: Bronchoconstriction was induced by anesthetic induction with
      propofol in two patients with allergic diseases. One had severe bronchospasm
      improved by epinephrine. Propofol should be used with caution in patients with
      allergic disease.

PMID- 11524334
TI  - Opioid overdose in a patient using a fentanyl patch during treatment with a
      warming blanket.
AB  - IMPLICATIONS: This case describes the narcotic overdose associated with the use
      of a fentanyl transdermal patch in a patient being rewarmed with an external
      warming blanket during surgery. The clinical manifestation and the presumed
      pharmacokinetic mechanism responsible for the fentanyl overdose are discussed.

PMID- 11524335
TI  - Improving standard cardiopulmonary resuscitation with an inspiratory impedance
      threshold valve in a porcine model of cardiac arrest.
AB  - To improve the efficiency of standard cardiopulmonary resuscitation (CPR), we
      evaluated the potential value of impeding respiratory gas exchange selectively
      during the decompression phase of standard CPR in a porcine model of ventricular
      fibrillation. After 6 min of untreated cardiac arrest, anesthetized farm pigs
      weighing 30 kg were randomized to be treated with either standard CPR with a sham
      valve (n = 11) or standard CPR plus a functional inspiratory impedance threshold
      valve (ITV(TM)) (n = 11). Coronary perfusion pressure (CPP) (diastolic aortic
      minus right atrial pressure) was the primary endpoint. Vital organ blood flow was
      assessed with radiolabeled microspheres after 6 min of CPR, and defibrillation
      was attempted 11 min after starting CPR. After 2 min of CPR, mean +/- SEM CPP was
      14 +/- 2 mm Hg with the sham valve versus 20 +/- 2 mm Hg in the ITV group (P <
      0.006). Significantly higher CPPs were maintained throughout the study when the
      ITV was used. After 6 min of CPR, mean +/- SEM left ventricular and global
      cerebral blood flows were 0.10 +/- 0.03 and 0.19 +/- 0.03 mL. min(-1). g(-1) in
      the Control group versus 0.19 +/- 0.03 and 0.26 +/- 0.03 mL. min(-1). g(-1) in
      the ITV group, respectively (P < 0.05). Fifteen minutes after successful
      defibrillation, 2 of 11 animals were alive in the Control group versus 6 of 11 in
      the ITV group (not significant). In conclusion, use of an inspiratory impedance
      valve during standard CPR resulted in a marked increase in CPP and vital organ
      blood flow after 6 min of cardiac arrest.

PMID- 11524336
TI  - Learning endotracheal intubation in a clinical skills learning center: a
      quantitative study.
AB  - This study aimed to develop statistical models describing the learning of
      endotracheal intubation (ETI). We collected data from 100 subjects undergoing ETI
      training with intubatable medical models and manikins (airway trainers). Trainees
      initially viewed a video about ETI and an instructor demonstrated the technique.
      Subjects then made up to 17 supervised trials. Each trial was scored as a success
      or failure; this score was the primary outcome used in analyses. Random effects
      and population-averaged logit models, and a learning model intended to quantify
      the relative contributions of failed and successful trials to the learning
      process, were fitted to the data. The logit models provided evidence of
      differences in difficulty between different airway trainers and differences in
      success rate related to previous ETI experience. Trainees became familiar with an
      airway trainer after multiple trials, as demonstrated by a 50% decrease in the
      odds of successful ETI when starting on a new trainer. The learning model
      indicated that a trainee learns about as much from 1 successful ETI as from 12
      (95% confidence interval, 2-23) failed trials. The results demonstrate the
      feasibility of statistical modeling of the learning of ETI and provide insight
      into the learning process.

PMID- 11524337
TI  - Fiberoptically-guided insertion of transtracheal catheters.
AB  - IMPLICATIONS: Regular use of the transtracheal catheter (TTC) both offers an
      opportunity for training for the difficult airway and facilitates elective
      endoscopic surgery. Fiberoptic guidance and exploratory puncture improve the
      insertion of the TTC.

PMID- 11524338
TI  - A simple and inexpensive nasal cannula to prevent rebreathing for spontaneously
      breathing patients under surgical drapes.
AB  - IMPLICATIONS: A new nasal cannula that provides oxygenation and suctioning
      simultaneously prevents rebreathing during surgery in spontaneously breathing
      patients under surgical drapes. When air is not suctioned, inspired CO(2) levels
      increase significantly, whereas suctioning prevents this increase. Expiratory
      CO(2), respiratory rate, heart rate, and arterial blood pressure remain stable
      regardless of suctioning.

PMID- 11524339
TI  - Hospital profitability per hour of operating room time can vary among surgeons.
AB  - The operating margins (i.e., profits) of hospitals are decreasing. An important
      aspect of a hospital's finances is the profitability of individual surgical
      cases, which is measured by contribution margin. We sought to determine the
      extent to which contribution margin per hour of operating room (OR) time can vary
      among surgeons. We retrospectively analyzed 2848 elective cases performed by 94
      surgeons at the Stanford University School of Medicine. For each case, we
      subtracted variable costs from the total payment to the hospital to compute
      contribution margin. We found moderate variability in contribution margin per
      hour of OR time among surgeons, relative to the variability in contribution
      margins per OR hour among each surgeon's cases (Cohen's f equaled 0.29, 95% lower
      confidence interval bound 0.27). Contribution margin per OR hour was negative for
      26% of the cases. These results have implications for hospitals for which OR
      utilization is extensive, and for which elective cases are only scheduled if they
      can be completed during regularly scheduled hours. To increase or achieve
      profitability, managers need to increase the hours of lucrative cases, rather
      than encourage surgeons to do more and more cases. Whether the variability in
      contribution margin among surgeons should be used to more optimally (profitably)
      allocate OR time depends on the scheduling objectives of the surgical suite.

PMID- 11524340
TI  - Differential secretion of atrial and brain natriuretic peptide in critically ill
      patients.
AB  - Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are cardiac
      hormones with natriuretic, vasorelaxant, and aldosterone-inhibiting properties.
      We analyzed the plasma of 178 critically ill patients for ANP, BNP, aldosterone,
      and serum sodium concentration, as well as serum and urine osmolality and sodium
      filtration fraction. Mean plasma concentrations of ANP and BNP were increased in
      critically ill patients compared with healthy controls (ANP, 14.3 +/- 5.8 pmol/L
      versus 8.8 +/- 3.2 pmol/L, P < 0.05; BNP, 26.2 +/- 10.7 pmol/L versus 4.6 +/- 2.8
      pmol/L, P < 0.0001). The relative increases in ANP concentrations were comparable
      in all diseases. BNP concentrations, by contrast, showed a wider variation. The
      largest BNP concentrations were observed in patients who underwent cardiac
      surgical procedures and in patients with subarachnoid hemorrhage. ANP, but not
      BNP, was correlated with aldosterone levels (r = 0.4, P < 0.001), serum sodium (r
      = 0.42, P < 0.001), sodium filtration fraction (r = 0.3, P < 0.001), serum
      osmolality (r = 0.25, P < 0.01), urinary osmolality (r = -0.24, P < 0.01), and
      central venous pressure (r = 0.22, P < 0.01). ANP and BNP concentrations were
      increased in critically ill patients; however, this did not correlate with the
      severity of illness or mortality. Our data support a regulatory role for ANP in
      the maintenance of water and electrolyte balance. The physiologic role of BNP, by
      contrast, is less clear. ANP and BNP are not predictors for the severity of
      illness and mortality in critically ill patients.

PMID- 11524341
TI  - A noninvasive investigation of muscle energetics supports similarities between
      exertional heat stroke and malignant hyperthermia.
AB  - Exertional heat stroke (EHS) is usually triggered by strenuous exercise performed
      under hot and humid environmental conditions. Although the pathogenesis of an EHS
      episode differs from that of a clinical malignant hyperthermia (MH) crisis, both
      conditions share some similarities in symptoms, such as the abnormal increase in
      core temperature. By use of (31)P magnetic resonance spectroscopy, we analyzed
      the muscle energetics of 26 post-EHS subjects for whom in vitro
      halothane/caffeine contracture tests were abnormal and investigated possible
      similarities with subjects susceptible to MH. An early decrease of pH was noted
      during the first minute of exercise in EHS subjects as compared with controls.
      EHS subjects were divided into two subgroups according to the diagnostic score
      previously developed for MH subjects. The 19 subjects (73%) with a score higher
      than 2 displayed significantly larger caffeine-induced and earlier ryanodine
      induced contractures on muscle biopsies as compared with the rest of the group (7
      subjects). The results demonstrate that muscle energetics are abnormal in
      subjects who have experienced EHS and suggest a possible link between MH and EH,
      although all EHS cannot be considered as MH.

PMID- 11524342
TI  - The influence of atracurium, cisatracurium, and mivacurium on the proliferation
      of two human cell lines in vitro.
AB  - We tested the influence of atracurium and cisatracurium (final concentrations: 0,
      0.96, 3.2, 9.6, 32, and 96 microM) on proliferation of human cells (hepatoma
      HepG2 cells and human umbilical vein endothelial cells) in vitro. In additional
      experiments, glutathione, N-acetylcysteine, or carboxyl esterase was added before
      the addition of either relaxant. The number of cells counted after 72 h of
      incubation was expressed as a percentage of the mean cell number in wells
      incubated without additives. Atracurium and cisatracurium progressively decreased
      cell proliferation in a concentration-dependent pattern. With human umbilical
      vein endothelial cells, atracurium or cisatracurium (3.2 microM) decreased the
      cell count to 67.7 % (SD, 14.8%) and 50% (SD, 8.6%), respectively. Cell
      proliferation was not inhibited by mivacurium. The results were similar to those
      with HepG2 cells. Glutathione, N-acetylcysteine, and carboxyl esterase partially
      reversed the effects of atracurium and cisatracurium. When incubated in a buffer
      with glutathione, atracurium decreased the number of glutathione-sulfhydryl
      groups. The findings that atracurium and cisatracurium inhibit proliferation of
      human cell lines in vitro, but that mivacurium does not, and that this effect is
      alleviated by glutathione and N-acetylcysteine, as well as by the carboxyl
      esterase, indicate that the inhibition may be caused by the reactive acrylate
      metabolites.

PMID- 11524343
TI  - The effects of topical and intravenous ketamine on cerebral arterioles in dogs
      receiving pentobarbital or isoflurane anesthesia.
AB  - To evaluate the effects of ketamine on cerebral arterioles, we used a closed
      cranial window technique in mechanically ventilated, anesthetized dogs. Fourteen
      dogs were assigned to one of the following two basal-anesthesia groups:
      pentobarbital 2 mg. kg(-1). h(-1) or isoflurane 0.5 MAC (n = 7 each). We
      administered three different concentrations of ketamine (10(-7), 10(-5), and 10(
      3) M) under the window and measured arteriolar diameters. For comparison, in
      another 14 dogs we examined the effect of systemic (IV) ketamine (1 mg/kg and 5
      mg/kg) using the same two basal anesthetics. We measured diameters before and
      after ketamine administration, and we evaluated the effect of ketamine on CO(2)
      reactivity of the cerebral arterioles. Neither topical nor systemic ketamine
      dilated pial arterioles in either basal-anesthesia group. CO(2) reactivity of
      pial arterioles was reduced under systemic ketamine in both basal-anesthesia
      groups. The results indicate that although ketamine does not dilate pial
      arteriolar diameters when topically or IV administered, IV ketamine does
      attenuate hypercapnic vasodilation in dogs under basal pentobarbital or
      isoflurane anesthesia. These results provide some insight that ketamine is
      suitable for supplementary neurosurgical anesthesia.

PMID- 11524344
TI  - Metaraminol infusion for maintenance of arterial blood pressure during spinal
      anesthesia for cesarean delivery: the effect of a crystalloid bolus.
AB  - We randomly allocated women having elective cesarean delivery to receive either
      no bolus (Control Group, n = 31) or 20 mL/kg lactated Ringer's solution (Bolus
      Group, n = 35) IV before spinal anesthesia. An infusion of metaraminol started at
      0.25 mg/min was titrated to maintain systolic arterial blood pressure in the
      target range 90%-100% of baseline. The total dose of metaraminol required up to
      the time of uterine incision was similar between the Control Group and the Bolus
      Group (3.62 +/- 1.20 vs 3.27 +/- 1.39 mg, P = 0.3). However, the Control Group
      required more metaraminol in the first 5 min (1.29 +/- 0.60 vs 0.96 +/- 0.58 mg,
      P = 0.025) and a faster maximum infusion rate (0.45 +/- 0.20 vs 0.32 +/- 0.13
      mg/min, P = 0.002) compared with the Bolus Group. There was no difference between
      groups in regards to changes in systolic arterial blood pressure or heart rate
      over time, or maternal or neonatal outcome. We conclude that when metaraminol is
      used to maintain arterial pressure during spinal anesthesia for cesarean
      delivery, crystalloid bolus is not essential provided that sufficient vasopressor
      is given in the immediate postspinal period.

PMID- 11524345
TI  - Rebound perioperative hyperkalemia in six patients after cessation of ritodrine
      for premature labor.
AB  - IMPLICATIONS: This report describes six patients who had marked hyperkalemia 60
      150 min after cessation of intravenous ritodrine, which had been administered for
      management of preterm labor. Abnormal electrocardiographic findings are very
      important clues for a prompt diagnosis of hyperkalemia.

PMID- 11524346
TI  - The use of a computer-based decision support system facilitates primary care
      physicians' management of chronic pain.
AB  - We tested whether computer-based decision support (CBDS) could enhance the
      ability of primary care physicians (PCPs) to manage chronic pain. Structured
      summaries were generated for 50 chronic pain patients referred by PCPs to a pain
      clinic. A pain specialist used a decision support system to determine appropriate
      pain therapy and sent letters to the referring physicians outlining these
      recommendations. Separately, five board-certified PCPs used a CBDS system to
      "treat" the 50 cases. A successful outcome was defined as one in which new or
      adjusted therapies recommended by the software were acceptable to the PCPs (i.e.,
      they would have prescribed it to the patient in actual practice). Two pain
      specialists reviewed the PCPs' outcomes and assigned medical appropriateness
      scores (0 = totally inappropriate to 10 = totally appropriate). One year later,
      the hospital database provided information on how the actual patients' pain was
      managed and the number of patients re-referred by their PCP to the pain clinic.
      On the basis of CBDS recommendations, the PCP subjects "prescribed" additional
      pain therapy in 213 of 250 evaluations (85%), with a medical appropriateness
      score of 5.5 +/- 0.1. Only 25% of these chronic pain patients were subsequently
      re-referred to the pain clinic within 1 yr. The use of a CBDS system may improve
      the ability of PCPs to manage chronic pain and may also facilitate screening of
      consults to optimize specialist utilization.

PMID- 11524347
TI  - The injectable cyclooxygenase-2-specific inhibitor parecoxib sodium has analgesic
      efficacy when administered preoperatively.
AB  - Preoperative administration of analgesics may prevent or reduce hyperalgesia and
      inhibit inflammation and pain by reducing the synthesis of prostaglandins in
      response to surgical injury. We evaluated in this placebo-controlled study the
      analgesic efficacy and safety of single doses of parecoxib sodium (20, 40, and 80
      mg IV) when administered before oral surgery. Efficacy assessments were recorded
      during the 24-h period after completion of surgery. All doses of parecoxib sodium
      were consistently and significantly superior to placebo as measured by time to
      rescue medication, proportion of patients requiring rescue medication, patient's
      global assessment, and pain intensity. There were no significant differences
      between the Parecoxib Sodium 40- and 80-mg groups, suggesting that the analgesic
      effect of preoperatively administered parecoxib sodium reaches a plateau at 40 mg
      in this model. Forty-eight percent of the Parecoxib Sodium 40-mg group required
      rescue medication in the 24-h study period, compared with 93% of patients in the
      Placebo group. Overall, there were fewer adverse events in parecoxib sodium
      treated patients compared with placebo. These findings suggest that preoperative
      administration of parecoxib sodium, the injectable prodrug of the cyclooxygenase
      2 specific inhibitor valdecoxib, is effective, safe, and well tolerated for
      treating postoperative pain.

PMID- 11524348
TI  - The release of spinal prostaglandin E2 and the effect of nitric oxide synthetase
      inhibition during strychnine-induced allodynia.
AB  - The removal of spinal glycinergic inhibition by intrathecal strychnine produces
      an allodynia-like state in rodents. Our objective was to measure spinal
      prostaglandin E2 (PGE2) release during strychnine-allodynia and examine the
      effects of Nomega-nitro-L-arginine (L-NOARG), an inhibitor of nitric oxide
      synthetase. Under halothane, rats were fitted with intrathecal and spinal
      microdialysis catheters, and microelectrodes implanted into the locus coeruleus
      for measurement of catechol oxidation current (CAOC) using voltammetry. Animals
      were then administered urethane and treated as follows: 1) baseline control 10
      min, intrathecal strychnine (40 microg) 10 min, 10 min of hair deflection, and 2)
      10-min control followed by intrathecal strychnine (40 microg) with hair
      deflection for 60 min. Spinal dialysate samples were collected for PGE2 levels
      determined by using immunoassay. In separate experiments, the effect of
      intrathecal strychnine (40 microg) followed by hair deflection was studied in
      rats pretreated with intrathecal l-NOARG (50 nmol). After intrathecal strychnine,
      hair deflection significantly increased spinal PGE2 release (619% +/- 143%),
      locus coeruleus CAOC (181% +/- 6%), and mean arterial pressure (123% +/- 2%) P <
      0.05. Pretreatment with intrathecal l-NOARG significantly inhibited strychnine
      allodynia. In this model, hair deflection evokes spinal PGE2 release, locus
      coeruleus activation, and an increase in mean arterial pressure. L-NOARG
      pretreatment attenuated the locus coeruleus CAOC, a biochemical index of
      strychnine-allodynia, suggesting a mediator role of nitric oxide. A mediator role
      of nitric oxide is also implicated, helping to explain the pathophysiology of
      this allodynic pain.

PMID- 11524349
TI  - The efficacy of epinephrine or vasopressin for resuscitation during epidural
      anesthesia.
AB  - Cardiopulmonary resuscitation (CPR) during epidural anesthesia is considered
      difficult because of diminished coronary perfusion pressure. The efficacy of
      epinephrine and vasopressin in this setting is unknown. Therefore, we designed
      this study to assess the effects of epinephrine versus vasopressin on coronary
      perfusion pressure in a porcine model with and without epidural anesthesia and
      subsequent cardiac arrest. Thirty minutes before induction of cardiac arrest, 16
      pigs received epidural anesthesia with bupivacaine while another 12 pigs received
      only saline administration epidurally. After 1 min of untreated ventricular
      fibrillation, followed by 3 min of basic life-support CPR, Epidural Animals and
      Control Animals randomly received every 5 min either epinephrine (45, 45, and 200
      microg/kg) or vasopressin (0.4, 0.4, and 0.8 U/kg). During basic life-support
      CPR, mean +/- SEM coronary perfusion pressure was significantly lower after
      epidural bupivacaine than after epidural saline (13 +/- 1 vs 24 +/- 2 mm Hg, P <
      0.05). Ninety seconds after the first drug administration, epinephrine increased
      coronary perfusion pressure significantly less than vasopressin in control
      animals without epidural block (42 +/- 2 vs 57 +/- 5 mm Hg, P < 0.05), but
      comparably to vasopressin after epidural block (45 +/- 4 vs 48 +/- 6 mm Hg).
      Defibrillation was attempted after 18 min of CPR. After return of spontaneous
      circulation, bradycardia required treatment in animals receiving vasopressin,
      especially with epidural anesthesia. Systemic acidosis was increased in animals
      receiving epinephrine than vasopressin, regardless of presence or absence of
      epidural anesthesia. We conclude that vasopressin may be a more desirable
      vasopressor for resuscitation during epidural block because the response to a
      single dose is longer lasting, and acidosis after multiple doses is less severe
      compared with epinephrine.

PMID- 11524350
TI  - Systemic toxicity and resuscitation in bupivacaine-, levobupivacaine-, or
      ropivacaine-infused rats.
AB  - We compared the systemic toxicity of bupivacaine, levobupivacaine, and
      ropivacaine in anesthetized rats. We also compared the ability to resuscitate
      rats after lethal doses of these local anesthetics. Bupivacaine, levobupivacaine,
      or ropivacaine was infused at a rate of 2 mg. kg(-1). min(-1) while
      electrocardiogram, electroencephalogram, and arterial pressure were continuously
      monitored. When asystole was recorded, drug infusion was stopped and a
      resuscitation sequence was begun. Epinephrine 0.01 mg/kg was administered at 1
      min intervals while external cardiac compressions were applied. Resuscitation was
      considered successful when a systolic arterial pressure > or =100 mm Hg was
      achieved within 5 min. The cumulative doses of levobupivacaine and ropivacaine
      that produced seizures were similar and were larger than those of bupivacaine.
      The cumulative doses of levobupivacaine that produced dysrhythmias and asystole
      were smaller than the corresponding doses of ropivacaine, but they were larger
      than those of bupivacaine. The number of successful resuscitations did not differ
      among groups. However, a smaller dose of epinephrine was required in the
      Ropivacaine group than in the other groups. We conclude that the systemic
      toxicity of levobupivacaine is intermediate between that of ropivacaine and
      bupivacaine when administered at the same rate and that ropivacaine-induced
      cardiac arrest appears to be more susceptible to treatment than that induced by
      bupivacaine or levobupivacaine.

PMID- 11524351
TI  - What constitutes an effective but safe initial dose of lidocaine to test a
      thoracic epidural catheter?
AB  - To investigate the effects of age and dose on the spread of thoracic epidural
      anesthesia, we placed thoracic epidural catheters in 50 surgical patients divided
      into groups by age (Group I [young], 18-51 yr; Group II [old], 56-80 yr) and
      randomly assigned patients to receive either 5 mL (A) or 9 mL (B) of 2% lidocaine
      (plain) injected via the epidural catheter. Hemodynamic variables were measured
      (heart rate, mean arterial blood pressure, noninvasive impedance cardiac index)
      at baseline and every 5 min for 30 min. Detectable blockade occurred within 8 min
      after injection of 3 + 2 mL or 3 + 6 mL in 48 of 50 patients. Maximum spread of
      analgesia to pinprick occurred 15-23 min after completion of local anesthetic
      injection and was significantly different between age and volume groups by two
      way analysis of variance (Group IA [young 5], 10.9 +/- 4.0 dermatomes; Group IIB
      [young 9], 13.9 +/- 4.5 dermatomes; Group IIA [old 5], 14.1 +/- 5.6 dermatomes;
      and Group IIB [old 9], 17.4 +/- 5.1 dermatomes). Minor decreases in mean arterial
      blood pressure (8%-17%) and heart rate (4%-11%) were noted. Two patients in the
      Old 9 group required IV ephedrine or ephedrine/atropine to treat hypotension and
      bradycardia. We conclude that given the rapid onset (3-8 min), extensive spread
      (11-14 dermatomal segments), and consistent hemodynamic stability, thoracic
      epidural anesthesia should be initiated with lidocaine 100 mg (5 mL 2% lidocaine)
      to establish proper location of the catheter in the epidural space in both
      younger and older patients.

PMID- 11524353
TI  - A systematic review of the peripheral analgesic effects of intraarticular
      morphine.
AB  - The analgesic effects of intraarticular morphine are controversial. To
      systematically evaluate the effects, we performed a review of the literature and
      a metaanalysis of the peripheral effects of morphine injected intraarticularly.
      Research databases were searched to identify articles in which peripheral
      analgesic effects of morphine were studied in patients undergoing arthroscopic
      knee procedures under local, regional, or general anesthesia. The review was
      performed on three issues: does morphine injected intraarticularly produce
      analgesia, is it a dose-dependent effect, and, if so, is the effect systemic or
      mediated via peripheral opioid receptors? Visual analog score (VAS) and analgesic
      consumption were studied during the early phase (0-2 h), intermediate phase (2-6
      h), and late phase (6-24 h) postoperatively after injection of morphine
      intraarticularly. Metaanalysis of these effect variables was performed by the
      weighted-analysis technique, and the essential homogeneity assumption was tested
      by the chi(2) test. Forty-five articles could be identified in which the effects
      of morphine were studied in a prospective, randomized manner, and 32 of these
      studies included a placebo control. Pooled analyses of data from 19 studies
      suitable for metaanalysis showed an improvement in analgesia after morphine
      compared with placebo in the order of 12-17 mm on the VAS during all three phases
      of treatment. Studies with high quality scores showed somewhat smaller
      improvements. Total analgesic consumption could not be analyzed statistically,
      but the number of studies showing decreased analgesic consumption or no
      differences between groups was identical (six and six). No clear dose-response
      effect was seen when VAS was used as a measure of pain, but it was seen when area
      under the curve was used as a measure of pain. A systemic effect of peripherally
      injected morphine was not possible to exclude because of the very limited data
      available. We conclude from this metaanalysis that intraarticularly administered
      morphine has a definite but mild analgesic effect. It may be dose dependent, and
      a systemic effect cannot be completely excluded.

PMID- 11524352
TI  - A comparison of epidural levobupivacaine 0.5% with or without epinephrine for
      lumbar spine surgery.
AB  - Levobupivacaine, the S(-) isomer of bupivacaine, is less cardiotoxic than racemic
      bupivacaine. In this prospective, randomized, double-blinded study of epidural
      anesthesia, we compared the onset, extent, and duration of sensory and motor
      blockade produced by plain 0.5% levobupivacaine (15 mL, 75 mg) with that of 0.5%
      levobupivacaine with the addition of 1:400,000 or 1:200,000 epinephrine in 117
      patients undergoing elective spine surgery. The time to onset of adequate sensory
      block (T10 dermatome) was similar in all groups (12.4 +/- 6.6 min for plain
      levobupivacaine, 13.9 +/- 7.9 min for levobupivacaine with 1:400,000 epinephrine,
      and 12.7 +/- 4.9 min for levobupivacaine with 1:200,000 epinephrine), with an
      average peak block height of T5. Time to complete regression of sensory blockade
      was also similar between groups (357 +/- 119 min for plain levobupivacaine, 378
      +/- 98 min for levobupivacaine with 1:400,000 epinephrine, and 348 +/- 80 min for
      levobupivacaine with 1:200,000 epinephrine). Peak serum levobupivacaine levels
      were reduced in each of the epinephrine-containing groups. We conclude that 0.5%
      levobupivacaine with or without 1:200,000 or 1:400,000 epinephrine produced
      effective epidural anesthesia in patients having lumbar spine surgery.
      Epinephrine 1:400,000 is as effective as 1:200,000 in reducing the resultant
      serum levobupivacaine levels after epidural anesthesia.

PMID- 11524354
TI  - The enhancement of sensory blockade by clonidine selectively added to mepivacaine
      after midhumeral block.
AB  - Clonidine added to local anesthetics results in an increased duration of
      anesthesia or analgesia after brachial plexus block. We investigated the effect
      of selective application of clonidine to the median and musculocutaneous nerves
      during midhumeral block, a technique allowing selective nerve blocks with the use
      of different local anesthetics. Initially, 58 patients scheduled for hand surgery
      were prospectively enrolled to receive a midhumeral block. These patients were
      randomly allocated into two groups. The Control group (n = 28) received 10 mL of
      plain mepivacaine 1.5% for each nerve (median, musculocutaneous, ulnar, and
      radial). The Clonidine group (n = 30) received 10 mL of plain mepivacaine 1.5%
      for each nerve, but the median and musculocutaneous nerves also received a dose
      of 50 microg clonidine. One patient in the Control group and two patients in the
      Clonidine group with a failed block were therefore excluded from the analysis.
      The onset time of surgical anesthesia was recorded. The durations of sensory and
      motor blocks were checked every 15 min. The plasma mepivacaine concentration was
      analyzed from 10 patients in each group. Onset times for complete sensory block
      were similar between the two groups. Adding 50 microg clonidine to the median and
      musculocutaneous nerves resulted in a significant increase in the duration of
      sensory block in these nerves (P < 0.0001). Recovery of motor block was not
      different between the two groups. No significant difference was found between the
      two groups in the mean plasma mepivacaine concentration.

PMID- 11524355
TI  - The relationship between pneumatic tourniquet time and the amount of pulmonary
      emboli in patients undergoing knee arthroscopic surgeries.
AB  - Near-fatal pulmonary embolism can occur immediately after tourniquet release
      after orthopedic surgeries. In this study, we determined the relationship between
      tourniquet time and the occurrence of pulmonary emboli in 30 patients undergoing
      arthroscopic knee surgeries, by using transesophageal echocardiography. The right
      atrium (RA) was continuously monitored by transesophageal echocardiography, and
      the number of emboli present was assessed with the following formula: Amount of
      emboli = 100 x [(total embolic area in the RA after tourniquet release) - (total
      area of emboli or artifact in the RA before tourniquet release)]/(RA area). The
      area was assessed 0-300 s after tourniquet release by using image-analysis
      software. The peak amount of emboli appeared approximately 50 s after tourniquet
      release. In addition, there was a significant correlation between amount of
      emboli (Ae [%]) and tourniquet time (Ttq [min]): (Ae = 0.1 x Ttq - 1.0, r =
      0.795, P < 0.01). This study suggests that acute pulmonary embolism may occur
      within 1 min of tourniquet release and that the number of emboli is dependent on
      Ttq.

PMID- 11524357
TI  - The pressor response and airway effects of cricoid pressure during induction of
      general anesthesia.
AB  - Cricoid pressure (CP) has been used to protect the patient from regurgitation and
      gastric insufflation. Because the hemodynamic effects of CP have not been
      evaluated independently, we designed this prospective study. Eighty ASA I adult
      patients were prospectively included in the study. Patients were randomly divided
      into Cricoid and Placebo groups. In the Cricoid group, after the induction of
      anesthesia, bimanual CP was performed, and in the Control group, simple placement
      of hands without exerting pressure was performed. Peak inspiratory pressure and
      exhaled tidal volume were recorded before and during the application of CP.
      Arterial blood pressure and heart rate were recorded before and after application
      of CP. The data were compared between and within groups by using the mixed-design
      analysis of variance. Peak inspiratory pressure increased and tidal volume
      decreased significantly after the application of CP compared with the Control
      group and baseline values. Arterial blood pressure and heart rate increased
      significantly after the application of CP compared with the baseline values and
      with those of the Control group. The result of this study shows that CP can cause
      a relatively strong pressor response.

PMID- 11524356
TI  - Prolonging viability of swine muscle biopsy specimens in malignant hyperthermia
      testing.
AB  - In North America, the caffeine halothane contracture test (CHCT) is the standard
      test for the diagnosis of malignant hyperthermia (MH). Current CHCT protocol
      recommends that the test be completed within 5 h of muscle excision. The purpose
      of this study was to investigate whether the period of skeletal muscle viability
      could be extended to 24 h. We tested the gracilis muscle from normal (n = 8) and
      MH-susceptible swine (n = 8). After baseline (1-2 h after excision) CHCT, the
      remaining muscles were placed into one of the following four treatment groups. In
      Groups 1 and 2, the muscles remained under tension and were stored in Krebs
      buffer (pH 7.4) at 23 degrees C-25 degrees C (clamped-warm) and 4 degrees C
      (clamped-cold), respectively. In Groups 3 and 4, the muscle strips were
      dissected, and the ends were tied with silk sutures, cut from the clamp, and
      placed in Krebs buffer at 23 degrees C-25 degrees C (free-warm) and 4 degrees C
      (free-cold), respectively. The responses of the treatment groups to halothane
      (3%) and caffeine (0.5-32 mM) were tested 22-26 h after excision. The clamped
      warm storage was the only storage method to correctly diagnose MH susceptibility
      in all muscle strips tested. This finding was also confirmed in muscle stored
      under clamped-warm conditions and shipped overnight to another testing center for
      a parallel CHCT.

PMID- 11524358
TI  - Atropine for the treatment of hiccup after laryngeal mask insertion.
AB  - IMPLICATIONS: We describe three patients in whom hiccups were treated
      successfully by atropine. Although further clinical investigation is needed,
      atropine may be useful in the treatment of hiccups after the laryngeal mask
      airway insertion.

PMID- 11524359
TI  - Fourteenth annual meeting of the Society for Pediatric Anesthesia, San Francisco,
      California, October 13, 2000.

PMID- 11524360
TI  - False negative BIS? Maybe, maybe not!

PMID- 11524361
TI  - Experimental cervical spine injury and airway management methods.

PMID- 11524362
TI  - Pediatric endotracheal tubes: the advantage of outer diameter.

PMID- 11524363
TI  - Rattling of unidirectional valves due to water obstructing the ventilator hose.

PMID- 11524364
TI  - Heparin effect after hepatic artery anastomosis during liver transplantation.

PMID- 11524365
TI  - Considerations in the use of COX-2 inhibitors in spinal fusion surgery.

PMID- 11524366
TI  - Grading intubation conditions: how and by whom?

PMID- 11524367
TI  - Extended femoral nerve sheath block after total hip arthroplasty.

PMID- 11524368
TI  - Generation of a database containing discordant intron positions in eukaryotic
      genes (MIDB).
AB  - MOTIVATION: Intron sliding is the relocation of intron-exon boundaries over short
      distances and is often also referred to as intron slippage or intron migration or
      intron drift. We have generated a database containing discordant intron positions
      in homologous genes (MIDB--Mismatched Intron DataBase). Discordant intron
      positions are those that are either closely located in homologous genes (within a
      window of 10 nucleotides) or an intron position that is present in one gene but
      not in any of its homologs. The MIDB database aims at systematically collecting
      information about mismatched introns in the genes from GenBank and organizing it
      into a form useful for understanding the genomics and dynamics of introns thereby
      helping understand the evolution of genes. RESULTS: Intron displacement or
      sliding is critically important for explaining the present distribution of
      introns among orthologous and paralogous genes. MIDB allows examining of intron
      movements and allows mapping of intron positions from homologous proteins onto a
      single sequence. The database is of potential use for molecular biologists in
      general and for researchers who are interested in gene evolution and eukaryotic
      gene structure. Partial analysis of this database allowed us to identify a few
      putative cases of intron sliding. AVAILABILITY:
      http://intron.bic.nus.edu.sg/midb/midb.html

PMID- 11524369
TI  - Representation of amino acids as five-bit or three-bit patterns for filtering
      protein databases.
AB  - MOTIVATION: We propose representing amino acids by bit-patterns so they may be
      used in a filter algorithm for similarity searches over protein databases, to
      rapidly eliminate non-homologous regions of database sequences. The filter
      algorithm would be based on dynamic programming optimization. It would have the
      advantage over previous filter algorithms that its substitution scoring function
      distinguishes between conservative and non-conservative amino acid substitutions.
      RESULTS: Simulated annealing was used to search for the best five-bit or three
      bit patterns to represent amino acids, where similar amino acids were given
      similar bit-patterns. The similarity between amino acids was estimated from the
      BLOSUM45 matrix. Representing amino acids by these five-bit and three-bit
      patterns, the Escherichia coli PhoE precursor and the bacteriophage PA2 LC
      precursor were aligned. The alignments were nearly the same as that obtained when
      BLOSUM45 was used to score substitutions. AVAILABILITY: The C code of the
      optimization algorithm for searching for the optimal bit-pattern representation
      of amino acids is available from the authors upon request.

PMID- 11524370
TI  - Amino acid similarity matrices based on force fields.
AB  - MOTIVATION: We propose a general method for deriving amino acid substitution
      matrices from low resolution force fields. Unlike current popular methods, the
      approach does not rely on evolutionary arguments or alignment of sequences or
      structures. Instead, residues are computationally mutated and their contribution
      to the total energy/score is collected. The average of these values over each
      position within a set of proteins results in a substitution matrix. RESULTS:
      Example substitution matrices have been calculated from force fields based on
      different philosophies and their performance compared with conventional
      substitution matrices. Although this can produce useful substitution matrices,
      the methodology highlights the virtues, deficiencies and biases of the source
      force fields. It also allows a rather direct comparison of sequence alignment
      methods with the score functions underlying protein sequence to structure
      threading. AVAILABILITY: Example substitution matrices are available from
      http://www.rsc.anu.edu.au/~zsuzsa/suppl/matrices.html. SUPPLEMENTARY INFORMATION:
      The list of proteins used for data collection and the optimized parameters for
      the alignment are given as supplementary material at
      http://www.rsc.anu.edu.au/~zsuzsa/suppl/matrices.html.

PMID- 11524371
TI  - AL2CO: calculation of positional conservation in a protein sequence alignment.
AB  - MOTIVATION: Amino acid sequence alignments are widely used in the analysis of
      protein structure, function and evolutionary relationships. Proteins within a
      superfamily usually share the same fold and possess related functions. These
      structural and functional constraints are reflected in the alignment conservation
      patterns. Positions of functional and/or structural importance tend to be more
      conserved. Conserved positions are usually clustered in distinct motifs
      surrounded by sequence segments of low conservation. Poorly conserved regions
      might also arise from the imperfections in multiple alignment algorithms and thus
      indicate possible alignment errors. Quantification of conservation by attributing
      a conservation index to each aligned position makes motif detection more
      convenient. Mapping these conservation indices onto a protein spatial structure
      helps to visualize spatial conservation features of the molecule and to predict
      functionally and/or structurally important sites. Analysis of conservation
      indices could be a useful tool in detection of potentially misaligned regions and
      will aid in improvement of multiple alignments. RESULTS: We developed a program
      to calculate a conservation index at each position in a multiple sequence
      alignment using several methods. Namely, amino acid frequencies at each position
      are estimated and the conservation index is calculated from these frequencies. We
      utilize both unweighted frequencies and frequencies weighted using two different
      strategies. Three conceptually different approaches (entropy-based, variance
      based and matrix score-based) are implemented in the algorithm to define the
      conservation index. Calculating conservation indices for 35522 positions in 284
      alignments from SMART database we demonstrate that different methods result in
      highly correlated (correlation coefficient more than 0.85) conservation indices.
      Conservation indices show statistically significant correlation between
      sequentially adjacent positions i and i + j, where j < 13, and averaging of the
      indices over the window of three positions is optimal for motif detection.
      Positions with gaps display substantially lower conservation properties. We
      compare conservation properties of the SMART alignments or FSSP structural
      alignments to those of the ClustalW alignments. The results suggest that
      conservation indices should be a valuable tool of alignment quality assessment
      and might be used as an objective function for refinement of multiple alignments.
      AVAILABILITY: The C code of the AL2CO program and its pre-compiled versions for
      several platforms as well as the details of the analysis are freely available at
      ftp://iole.swmed.edu/pub/al2co/.

PMID- 11524372
TI  - Evaluation of protein multiple alignments by SAM-T99 using the BAliBASE multiple
      alignment test set.
AB  - MOTIVATION: SAM-T99 is an iterative hidden Markov model-based method for finding
      proteins similar to a single target sequence and aligning them. One of its main
      uses is to produce multiple alignments of homologs of the target sequence.
      Previous tests of SAM-T99 and its predecessors have concentrated on the quality
      of the searches performed, not on the quality of the multiple alignment. In this
      paper we report on tests of multiple alignment quality, comparing SAM-T99 to the
      standard multiple aligner, CLUSTALW. RESULTS: The paper evaluates the multiple
      alignment aspect of the SAM-T99 protocol, using the BAliBASE benchmark alignment
      database. On these benchmarks, SAM-T99 is comparable in accuracy with ClustalW.
      AVAILABILITY: The SAM-T99 protocol can be run on the web at
      http://www.cse.ucsc.edu/research/compbio/HMM-apps/T99-query.html and the
      alignment tune-up option described here can be run at
      http://www.cse.ucsc.edu/research/compbio/HMM-apps/T99-tuneup.html. The protocol
      is also part of the standard SAM suite of tools.
      http://www.cse.ucsc.edu/research/compbio/sam/

PMID- 11524373
TI  - Support vector machine approach for protein subcellular localization prediction.
AB  - MOTIVATION: Subcellular localization is a key functional characteristic of
      proteins. A fully automatic and reliable prediction system for protein
      subcellular localization is needed, especially for the analysis of large-scale
      genome sequences. RESULTS: In this paper, Support Vector Machine has been
      introduced to predict the subcellular localization of proteins from their amino
      acid compositions. The total prediction accuracies reach 91.4% for three
      subcellular locations in prokaryotic organisms and 79.4% for four locations in
      eukaryotic organisms. Predictions by our approach are robust to errors in the
      protein N-terminal sequences. This new approach provides superior prediction
      performance compared with existing algorithms based on amino acid composition and
      can be a complementary method to other existing methods based on sorting signals.
      AVAILABILITY: A web server implementing the prediction method is available at
      http://www.bioinfo.tsinghua.edu.cn/SubLoc/. SUPPLEMENTARY INFORMATION:
      Supplementary material is available at
      http://www.bioinfo.tsinghua.edu.cn/SubLoc/.

PMID- 11524374
TI  - The Bioinformatics Template Library--generic components for biocomputing.
AB  - MOTIVATION: The efficiency of bioinformatics programmers can be greatly increased
      through the provision of ready-made software components that can be rapidly
      combined, with additional bespoke components where necessary, to create finished
      programs. The new standard for C++ includes an efficient and easy to use library
      of generic algorithms and data-structures, designed to facilitate low-level
      component programming. The extension of this library to include functionality
      that is specifically useful in compute-intensive tasks in bioinformatics and
      molecular modelling could provide an effective standard for the design of
      reusable software components within the biocomputing community. RESULTS: A novel
      application of generic programming techniques in the form of a library of C++
      components called the Bioinformatics Template Library (BTL) is presented. This
      library will facilitate the rapid development of efficient programs by providing
      efficient code for many algorithms and data-structures that are commonly used in
      biocomputing, in a generic form that allows them to be flexibly combined with
      application specific object-oriented class libraries. AVAILABILITY: The BTL is
      available free of charge from our web site http://www.cryst.bbk.ac.uk/~classlib/
      and the EMBL file server http://www.embl-ebi.ac.uk/FTP/index.html

PMID- 11524375
TI  - Genotype transposer: automated genotype manipulation for linkage disequilibrium
      analysis.
AB  - The purpose of this work is to provide the modern molecular geneticist with tools
      to perform more efficient and more accurate analysis of the genotype data they
      produce. By using Microsoft Excel macros written in Visual Basic, we can
      translate genotype data into a form readable by the versatile software
      'Arlequin', read the Arlequin output, calculate statistics of linkage
      disequilibrium, and put the results in a format for viewing with the software
      'GOLD'. AVAILABILITY: The software is available by FTP at:
      ftp://xcsg.iarc.fr/cox/Genotype_Transposer/. SUPPLEMENTARY INFORMATION: Detailed
      instruction and examples are available at:
      ftp://xcsg.iarc.fr/cox/Genotype&_Transposer/. Arlequin is available at:
      http://lgb.unige.ch/arlequin/. GOLD is available at:
      http://www.well.ox.ac.uk/asthma/GOLD/.

PMID- 11524376
TI  - Polylink: to support two-point linkage analysis in autotetraploids.
AB  - SUMMARY: Polylink runs under Microsoft Windows (95 or later). It performs various
      calculations that are useful for investigating two-point linkage analysis for
      autopolyploids, based on the random chromosome pairing model. These include
      calculation of offspring phenotypic probabilities as functions of the
      recombination fraction, calculation of theoretical standard errors for the
      maximum likelihood estimator of and numerical computation of maximum likelihood
      estimates. It also includes simulation facilities. AVAILABILITY: Polylink is free
      and available from Xiangming Xu via email

PMID- 11524377
TI  - GRR: graphical representation of relationship errors.
AB  - SUMMARY: A graphical tool for verifying assumed relationships between individuals
      in genetic studies is described. GRR can detect many common errors using
      genotypes from many markers. AVAILABILITY: GRR is available at
      http://bioinformatics.well.ox.ac.uk/GRR.

PMID- 11524378
TI  - Multi-query sequence BLAST output examination with MuSeqBox.
AB  - SUMMARY: MuSeqBox is a program to parse BLAST output and store attributes of
      BLAST hits in tabular form. The user can apply a number of selection criteria to
      filter out hits with particular attributes. MuSeqBox provides a powerful
      annotation tool for large sets of query sequences that are simultaneously
      compared against a database with any of the standard stand-alone or network
      client BLAST programs. We discuss such application to the problem of annotation
      and analysis of EST collections. AVAILABILITY: The program was written in
      standard C++ and is freely available to noncommercial users by request from the
      authors. The program is also available over the web at
      http://bioinformatics.iastate.edu/bioinformatics2go/mb/MuSeqBox.html.

PMID- 11524379
TI  - DBAli: a database of protein structure alignments.
AB  - SUMMARY: The DBAli database includes approximately 35000 alignments of pairs of
      protein structures from SCOP (Lo Conte et al., Nucleic Acids Res., 28, 257-259,
      2000) and CE (Shindyalov and Bourne, Protein Eng., 11, 739-747, 1998). DBAli is
      linked to several resources, including Compare3D (Shindyalov and Bourne,
      http://www.sdsc.edu/pb/software.htm, 1999) and ModView (Ilyin and Sali,
      http://guitar.rockefeller.edu/ModView/, 2001) for visualizing sequence alignments
      and structure superpositions. A flexible search of DBAli by protein sequence and
      structure properties allows construction of subsets of alignments suitable for a
      number of applications, such as benchmarking of sequence-sequence and sequence
      structure alignment methods under a variety of conditions. AVAILABILITY:
      http://guitar.rockefeller.edu/DBAli/

PMID- 11524380
TI  - HOMSTRAD: adding sequence information to structure-based alignments of homologous
      protein families.
AB  - summary: We describe an extension to the Homologous Structure Alignment Database
      (HOMSTRAD; Mizuguchi et al., Protein Sci., 7, 2469-2471, 1998a) to include
      homologous sequences derived from the protein families database Pfam (Bateman et
      al., Nucleic Acids Res., 28, 263-266, 2000). HOMSTRAD is integrated with the
      server FUGUE (Shi et al., submitted, 2001) for recognition and alignment of
      homologues, benefitting from the combination of abundant sequence information and
      accurate structure-based alignments. AVAILABILITY The HOMSTRAD database is
      available at: http://www-cryst.bioc.cam.ac.uk/homstrad/. Query sequences can be
      submitted to the homology recognition/alignment server FUGUE at: http://www
      cryst.bioc.cam.ac.uk/fugue/.

PMID- 11524381
TI  - Structure prediction meta server.
AB  - The Structure Prediction Meta Server offers a convenient way for biologists to
      utilize various high quality structure prediction servers available worldwide.
      The meta server translates the results obtained from remote services into uniform
      format, which are consequently used to request a jury prediction from a remote
      consensus server Pcons. AVAILABILITY: The structure prediction meta server is
      freely available at http://BioInfo.PL/meta/, some remote servers have however
      restrictions for non-academic users, which are respected by the meta server.
      SUPPLEMENTARY INFORMATION: Results of several sessions of the CAFASP and
      LiveBench programs for assessment of performance of fold-recognition servers
      carried out via the meta server are available at http://BioInfo.PL/services.html.

PMID- 11524382
TI  - Easier threading through web-based comparisons and cross-validations.
AB  - We have developed a WWW server for the integration and comparison of protein
      structure predictions performed by five different servers. Users submit an amino
      acid sequence to a selected set of these prediction methods. Results are gathered
      on a web-based page in order to facilitate comparison and analysis. All the
      alignments are further evaluated through a common threading tool making their
      comparisons easier. AVAILABILITY: The meta-server is available free at
      http://www.infobiosud.cnrs.fr/bioserver SUPPLEMENTARY INFORMATION:
      http://www.infobiosud.cnrs.fr/bioserver/hah1.html

PMID- 11524383
TI  - MRBAYES: Bayesian inference of phylogenetic trees.
AB  - SUMMARY: The program MRBAYES performs Bayesian inference of phylogeny using a
      variant of Markov chain Monte Carlo. AVAILABILITY: MRBAYES, including the source
      code, documentation, sample data files, and an executable, is available at
      http://brahms.biology.rochester.edu/software.html.

PMID- 11524384
TI  - SIR: a simple indexing and retrieval system for biological flat file databases.
AB  - SUMMARY: SIR is a Simple Indexing and Retrieval tool for indexing and searching
      biological flat file databases. SIR is a cross-platform solution entirely written
      in Python. Since the package is very small and installation is trivial, this
      would be an ideal solution for database providers to provide a custom retrieval
      tool to access them. AVAILABILITY: The modules will be made available at
      http://www.EMBLHeidelberg.de/~chenna/PySAT/sir.html

PMID- 11524386
TI  - C-reactive protein: linking inflammation to cardiovascular complications.

PMID- 11524387
TI  - Annulus paradoxus: transmitral flow velocity to mitral annular velocity ratio is
      inversely proportional to pulmonary capillary wedge pressure in patients with
      constrictive pericarditis.
AB  - BACKGROUND: The early diastolic velocity of the mitral annulus (E') is reduced in
      patients with diastolic dysfunction and increased filling pressures. Because
      transmitral inflow early velocity (E) increases progressively with higher filling
      pressures, E/E' has been shown to have a strong positive relationship with
      pulmonary capillary wedge pressure (PCWP) and left ventricular end-diastolic
      pressure. However, previous studies have primarily involved patients without a
      pericardial abnormality. In constrictive pericarditis (CP), E' is not reduced,
      despite increased filling pressures. This study evaluated the relationship
      between E/E' and PCWP in patients with CP. METHODS AND RESULTS: We studied 10
      patients (8 men; mean age, 64+/-7 years) with surgically confirmed CP. Doppler
      echocardiography was performed to measure early and late diastolic transmitral
      flow velocities. Tissue Doppler echocardiography was performed to measure E'.
      PCWP was measured with right heart catheterization. All patients were in sinus
      rhythm. Mean E and E' were 91+/-15 cm/s and 11+/-4 cm/s, respectively. Mean PCWP
      was 25+/-6 mm Hg. E' was positively correlated with PCWP (r=0.69, P=0.027). There
      was a significant inverse correlation between E/E' and PCWP (r=-0.74, P=0.014).
      Despite high left ventricular filling pressures, E/E' (mean, 9+/-4) was <15 in
      all but 1 patient. CONCLUSIONS: Paradoxical to the positive correlation between
      E/E' and PCWP in patients with myocardial disease, an inverse relationship was
      found in patients with CP.

PMID- 11524388
TI  - Activation of signal transducer and activator of transcription 3 protects
      cardiomyocytes from hypoxia/reoxygenation-induced oxidative stress through the
      upregulation of manganese superoxide dismutase.
AB  - BACKGROUND: Mice with cardiac-specific overexpression of signal transducer and
      activator of transcription 3 (STAT3) are resistant to doxorubicin-induced damage.
      The STAT3 signal may be involved in the detoxification of reactive oxygen species
      (ROS). METHODS AND RESULTS: The effects of leukemia inhibitory factor (LIF) or
      adenovirus-mediated transfection of constitutively activated STAT3 (caSTAT3) on
      the intracellular ROS formation induced by hypoxia/reoxygenation (H/R) were
      examined using rat neonatal cardiomyocytes. Either LIF treatment or caSTAT3
      significantly suppressed the increase of H/R-induced ROS evaluated by 2',7'
      dichlorofluorescin diacetate fluorescence. To assess whether ROS are really
      involved in H/R-induced cardiomyocyte injury, the amount of creatine
      phosphokinase in cultured medium was examined. Both LIF treatment and caSTAT3
      significantly decreased H/R-induced creatine phosphokinase release. These results
      indicate that the gp130/STAT3 signal protects H/R-induced cardiomyocyte injury by
      scavenging ROS generation. To investigate the mechanism of scavenging ROS, the
      effects of LIF on the induction of antioxidant enzymes were examined. LIF
      treatment significantly increased the expression of manganese superoxide
      dismutase (MnSOD) mRNA, whereas the expression of the catalase and glutathione
      peroxidase genes were unaffected. This induction of MnSOD mRNA expression was
      completely blocked by adenovirus-mediated transfection of dominant-negative
      STAT3. Moreover, caSTAT3 augmented MnSOD mRNA and its enzyme activity. In
      addition, the antisense oligodeoxyribonucleotide to MnSOD significantly inhibited
      both LIF and caSTAT3-mediated protective effects. CONCLUSIONS: The activation of
      STAT3 induces a protective effect on H/R-induced cardiomyocyte damage, mainly by
      inducting MnSOD. The STAT3-mediated signal is proposed as a therapeutical target
      of ROS-induced cardiomyocyte injury.

PMID- 11524389
TI  - Improvement of left ventricular remodeling and function by hydroxymethylglutaryl
      coenzyme a reductase inhibition with cerivastatin in rats with heart failure
      after myocardial infarction.
AB  - BACKGROUND: Hydroxymethylglutaryl coenzyme A reductase inhibitors (statins)
      attenuate angiotensin II-induced cellular signaling. Because angiotensin II is
      involved in left ventricular (LV) remodeling after myocardial infarction (MI), we
      examined the effects of statin treatment in an experimental model of chronic
      heart failure after MI. METHODS AND RESULTS: Rats with extensive MI were treated
      with placebo or cerivastatin (0.3 mg/kg per day) as a dietary supplement or via
      gavage for 11 weeks starting on the 7th postoperative day. Infarct size and
      cholesterol levels were similar among all groups. LV cavity area, an index of LV
      dilatation, was reduced in MI rats on cerivastatin compared with placebo. LV end
      diastolic pressure was increased in MI rats on placebo (24.1+/-4.1 mm Hg versus
      sham: 5.1+/-0.3 mm Hg; P<0.01), and it was significantly reduced by cerivastatin
      treatment (13.7+/-2.7 mm Hg; P<0.05 versus placebo). Cerivastatin partially
      normalized LV dP/dt(max) and dP/dt(min), indices of LV systolic and diastolic
      function, which were significantly reduced in MI rats on placebo. Improvement of
      LV function by cerivastatin was accompanied by a reduced expression of collagen
      type I and beta-myosin heavy chain. LV endothelial nitric oxide synthase was
      increased, whereas the nitrotyrosine protein level was decreased in MI rats by
      cerivastatin treatment. CONCLUSIONS: Cerivastatin improved LV remodeling and
      function in rats with heart failure. This effect was associated with an
      attenuated LV expression of fetal myosin heavy chain isoenzymes and collagen I.
      Statin treatment may retard the progression of chronic heart failure.

PMID- 11524390
TI  - Association of heart rate variability with occupational and environmental
      exposure to particulate air pollution.
AB  - BACKGROUND: Airborne particulate matter has been linked to excess morbidity and
      mortality. Recent attention has focused on the effects of particulate exposure on
      cardiac autonomic control. Inhaled particulates may affect the autonomic nervous
      system either directly, by eliciting a sympathetic stress response, or
      indirectly, through inflammatory cytokines produced in the lungs and released
      into the circulation. METHODS AND RESULTS: This longitudinal study examined the
      association of particulates </=2.5 microm in diameter (PM(2.5)) with heart rate
      variability (HRV) in an occupational cohort (N=40). Continuous monitoring of
      exposure and HR was performed during and away from work. PM(2.5) levels were
      higher than ambient levels typically reported in Boston, 0.167+/-3.205 mg/m(3)
      (geometric mean+/-geometric SD). We found a 2.66% decrease (95% CI, -3.75% to 
      1.58%) in the 5-minute SD of normal RR intervals (SDNN) for every 1 mg/m(3)
      increase in the 4-hour moving PM(2.5) average and a 1.02% increase (95% CI, 0.59%
      to 1.46%) in HR after adjusting for potential confounding factors. The decrease
      in SDNN became larger as the averaging interval increased. CONCLUSIONS: Workers
      experienced altered cardiac autonomic control after exposure to occupational and
      environmental PM(2.5). There appears to be either a long-acting (several hours)
      and a short-acting (several minutes) component to the mechanism of action that
      may be related to the production of cytokines and the sympathetic stress
      response, respectively, or a cumulative effect that begins shortly after exposure
      begins. The clinical significance of these effects in a healthy working
      population is unclear.

PMID- 11524391
TI  - Incremental prognostic value of elevated baseline C-reactive protein among
      established markers of risk in percutaneous coronary intervention.
AB  - BACKGROUND: Established methods of risk assessment in percutaneous coronary
      intervention have focused on clinical and anatomical lesion characteristics.
      Emerging evidence indicates the substantial contribution of inflammatory
      processes to short-term and long-term outcomes in coronary artery disease.
      METHODS AND RESULTS: Within a single-center registry of contemporary percutaneous
      coronary revascularization strategies with postprocedural creatine kinase and
      clinical events routinely recorded, we assessed the association of baseline C
      reactive protein with death or myocardial infarction within the first 30 days.
      Predictive usefulness of baseline C-reactive protein within the context of
      established clinical and angiographic predictors of risk was also examined. Among
      727 consecutive patients, elevated baseline C-reactive protein before
      percutaneous coronary intervention was associated with progressive increase in
      death or myocardial infarction at 30 days (lowest quartile, 3.9%, versus highest
      quartile, 14.2%; P=0.002). Among clinical and procedural characteristics,
      baseline C-reactive protein remained independently predictive of adverse events,
      with the highest quartile of C-reactive protein associated with an odds ratio for
      excess 30-day death or myocardial infarction of 3.68 (95% CI, 1.51 to 8.99;
      P=0.004). A predictive model that included baseline C-reactive protein quartiles,
      American College of Cardiology/American Heart Association lesion score, acute
      coronary syndrome presentation, and coronary stenting appears strongly predictive
      of 30-day death or myocardial infarction within this population (C-statistic,
      0.735) and among individual patients (Brier score, 0.006). CONCLUSIONS: Elevated
      baseline C-reactive protein portends heightened risk of 30-day death or
      myocardial infarction after coronary intervention. Coupled anatomic, clinical,
      and inflammatory risk stratification demonstrates strong predictive utility among
      patients undergoing percutaneous coronary intervention and may be useful for
      guiding future strategies.

PMID- 11524392
TI  - Relation between Gd-DTPA contrast enhancement and regional inotropic response in
      the periphery and center of myocardial infarction.
AB  - BACKGROUND: Gd-DTPA contrast-enhanced (CE) MRI identifies patterns of early
      hypoenhancement and delayed hyperenhancement in acute myocardial infarction, but
      their clinical significance for the prediction of myocardial viability remains
      controversial. Therefore, we closely examined the relationship between these CE
      patterns and regional inotropic response to low-dose dobutamine infusion at a
      regional level. METHODS AND RESULTS: Thirteen dogs underwent CE and tagged MRI at
      rest and during 5 microg. kg(-1). min(-1) dobutamine 48 hours after MI. CE
      patterns and 3D regional strains were measured in 96 segments per animal.
      Segments were categorized as being normofunctional (n=828) if resting
      circumferential shortening was within the range of remote myocardium, or
      dysfunctional (n=420) if not. Inotropic response in resting dysfunctional
      segments was assessed according to CE patterns. Significant improvement of radial
      thickening (from +12+/-1% [mean+/-SEM] to +22+/-2%, P<0.05) and circumferential
      shortening (from +1+/-1% to -5+/-1%, P<0.05) strains occurred in dysfunctional
      myocardium with normal CE pattern but not in myocardium with early
      hypoenhancement. Delayed hyperenhanced myocardium displayed a more complex
      behavior. Circumferential stretching improved in the peripheral regions (from
      +4+/-1% to -2+/-2%, P<0.05), where the infarct was nontransmural (38+/-3%
      transmurality), but not in centrally hyperenhanced regions (from +4+/-1% to +1+/
      1% P=NS), where the infarct was 66+/-3% transmural. CONCLUSIONS: Inotropic
      reserve was confined to dysfunctional myocardium with normal contrast enhancement
      but not to myocardium with early hypoenhancement. Inotropic response in delayed
      hyperenhanced myocardium is influenced by transmurality of necrosis. These
      observations support the use of CE MRI for the clinical detection of myocardial
      viability.

PMID- 11524393
TI  - Online myocardial viability assessment in the catheterization laboratory via NOGA
      electroanatomic mapping: Quantitative comparison with thallium-201 uptake.
AB  - BACKGROUND: The aim of this prospective study was to investigate the concordance
      between quantitative resting (201)Tl uptake as an established myocardial
      viability index and the electrical activity of the heart, determined by NOGA
      nonfluoroscopic electroanatomic mapping. METHODS AND RESULTS: The myocardial
      resting and late resting thallium uptakes of 384 myocardial segments from 32
      patients (27 males aged 65+/-8 years) with previous myocardial infarction and
      chronic stable angina were compared with unipolar voltage potentials and local
      shortening of the left ventricle as assessed by electroanatomic mapping. The
      quantitative thallium uptake data were analyzed by polar map analysis by division
      into 12 comparable myocardial segments, as represented in electroanatomic mapping
      images. Unipolar voltage potentials exhibited a significant logarithmic
      correlation with both resting and late resting thallium uptake (attenuation
      corrected: r=0.660 and r=0.744; non-attenuation corrected: r=0.623 and r=0.721).
      Receiver operator characteristic analyses revealed unipolar voltage cutoff points
      of 12.0 mV (predictive accuracy 0.853, P< 0.001; sensitivity/specificity 81%) for
      normal myocardium and 6.4 mV (predictive accuracy 0.901, P< 0.001;
      sensitivity/specificity 82%) for nonviable myocardium assessed by attenuation
      corrected (201)Tl late resting images and of 12.7 mV (predictive accuracy 0.822,
      P<0.001; sensitivity/specificity 75%) and 6.5 mV (predictive accuracy 0.808,
      P<0.001; sensitivity/specificity 73%) for non-attenuation-corrected late resting
      (201)Tl images. CONCLUSIONS: These results indicate that the unipolar voltage
      potentials obtained by electroanatomic mapping correlate well with standard
      quantitative late resting (201)Tl imaging for the evaluation of myocardial
      viability; thus, NOGA endocardial mapping provides useful "online" data at the
      time of catheterization, especially when information from other methods for
      viability assessment is unavailable.

PMID- 11524394
TI  - Patients with end-stage congestive heart failure treated with beta-adrenergic
      receptor antagonists have improved ventricular myocyte calcium regulatory protein
      abundance.
AB  - BACKGROUND: Alterations in Ca(2+)-handling proteins are thought to underlie the
      deranged Ca(2+) transients that contribute to deterioration of cardiac function
      in congestive heart failure (CHF). Clinical trials in CHF patients have shown
      that treatment with beta-adrenergic receptor antagonists (betaB) improves cardiac
      performance. The present study determined whether the abundance of Ca(2+)
      handling proteins is different in failing hearts from patients treated or
      untreated with beta B. METHODS AND RESULTS: Ca(2+) regulatory protein abundance
      was compared in LV myocardium of 10 nonfailing hearts (NF group) and 44 failing
      hearts (CHF group) removed at transplantation. Analysis was performed in betaB
      treated (betaB-CHF) and non-betaB treated (non-betaB-CHF) patients and in 4
      subgroups: ischemic cardiomyopathy (ICM, n=10), nonischemic dilated
      cardiomyopathy (DCM, n=10), ICM with betaB therapy (betaB-ICM, n=12), and DCM
      with betaB therapy (betaB-DCM, n=12). Sarcoplasmic reticulum Ca(2+) ATPase,
      phospholamban, and Na(+)-Ca(2+) exchanger protein abundance were determined by
      use of Western blot analysis. Ca(2+) transients were measured with fluo-3.
      Sarcoplasmic reticulum Ca(2+) ATPase was significantly less abundant whereas
      phospholamban and Na(+)-Ca(2+) exchanger were not significantly altered in non
      betaB-CHF versus NF. Sarcoplasmic reticulum Ca(2+) ATPase in the betaB-ICM and
      betaB-DCM was greater than in non-betaB-CHF and were not different than in NF.
      Ca(2+) transients in non-betaB-CHF myocytes had significantly smaller peaks and
      were prolonged versus NF myocytes. Ca(2+) transients from betaB-CHF myocytes had
      shorter durations than in betaB-CHF myocytes. CONCLUSIONS: betaB treatment in CHF
      patients can normalize the abundance of myocyte Ca(2+) regulatory proteins and
      improve Ca(2+)-handling.

PMID- 11524395
TI  - Subvalvular gradients in patients with valvular aortic stenosis: prevalence,
      magnitude, and physiological importance.
AB  - BACKGROUND: Although subvalvular gradients in patients with aortic stenosis have
      been described, their behavior and response to exercise have not been well
      characterized. METHODS AND RESULTS: Left ventricular and aortic pressures and
      linear flow velocity were measured with a catheter-tip manometer at rest and
      during supine exercise in 27 patients with valvular aortic stenosis. A
      subvalvular gradient was measured in each patient that represented, on average,
      48% of the total resting transvalvular gradient. With exercise, both total (rest:
      80+/-26 mm Hg; exercise: 90+/-25 mm Hg) and subvalvular gradients (rest: 37+/-13
      mm Hg; exercise: 60+/-22 mm Hg) increased significantly. There was a significant
      inverse relationship between change in exercise cardiac output and total and
      subvalvular gradients. However, only the exercise subvalvular gradient predicted
      cardiac output response. CONCLUSIONS: Subvalvular pressure gradients are
      universally present in patients with severe aortic stenosis and comprise
      approximately half of the total transvalvular gradient. The extent of exercise
      cardiac output increase is inversely related to the subvalvular gradient
      magnitude.

PMID- 11524396
TI  - Atrial therapies reduce atrial arrhythmia burden in defibrillator patients.
AB  - BACKGROUND: Approximately 25% of patients who receive an implantable cardioverter
      defibrillator (ICD) to treat ventricular tachyarrhythmias have documented atrial
      tachyarrhythmias before implantation. This study assessed the ability of device
      based prevention and termination therapies to reduce the burden of spontaneous
      atrial tachyarrhythmias. METHODS AND RESULTS: Patients with a standard indication
      for the implantation of an ICD and 2 episodes of atrial tachyarrhythmias in the
      preceding year received a dual-chamber ICD (Medtronic 7250 Jewel AF) that uses
      pacing and shock therapies for prevention and/or termination of atrial
      tachyarrhythmias. In a multicenter trial, patients were randomized to 3-month
      periods with atrial therapies "on" or "off" and subsequently crossed over.
      Analysis was performed on the 52 of 269 patients who had episodes of atrial
      tachyarrhythmia and had >/=30 days of follow-up with atrial therapies on and off.
      The atrial therapies resulted in a reduction of atrial tachyarrhythmia burden
      from a mean of 58.5 to 7.8 h/mo. A paired analysis (Wilcoxon signed-rank test)
      showed that the median difference in burden (1.1 h/mo) was highly significant
      (P=0.007). When the subgroup of 41 patients treated only with atrial pacing
      therapies was analyzed, the reduction in burden persisted (P=0.01). CONCLUSIONS:
      In this study, patients with a standard ICD indication and atrial
      tachyarrhythmias had a significant reduction in atrial tachyarrhythmia burden
      with use of atrial pacing and shock therapies.

PMID- 11524397
TI  - Staphylococcus aureus bacteremia in patients with permanent pacemakers or
      implantable cardioverter-defibrillators.
AB  - BACKGROUND: Although cardiac device infections (CDIs) are a devastating
      complication of permanent pacemakers or implantable cardioverter-defibrillators,
      the incidence of CDI in patients with bacteremia is not well defined. The
      objective of this study was to determine the incidence of CDI among patients with
      permanent pacemakers or implantable cardioverter-defibrillators who develop
      Staphylococcus aureus bacteremia (SAB). METHODS AND RESULTS: A cohort of all
      adult patients with SAB and permanent pacemakers or implantable cardioverter
      defibrillators over a 6-year period was evaluated prospectively. The overall
      incidence of confirmed CDI was 15 of 33 (45.4%). Confirmed CDI occurred in 9 of
      the 12 patients (75%) with early SAB (<1 year after device placement). Fifteen of
      21 patients (71.5%) with late SAB (>/=1 year after device placement) had either
      confirmed (6 of 21, 28.5%) or possible (9 of 21, 43%) CDI. In 60% of the patients
      (9 of 15) with confirmed CDI, no local signs or symptoms suggesting generator
      pocket infection were noted. CONCLUSIONS: The incidence of CDI among patients
      with SAB and cardiac devices is high. Neither physical examination nor
      echocardiography can exclude the possibility of CDI. In patients with early SAB,
      the device is usually involved, and approximately 40% of these patients have
      obvious clinical signs of cardiac device involvement. Conversely, in patients
      with late SAB, the cardiac device is rarely the initial source of bacteremia, and
      there is a paucity of local signs of device involvement. The cardiac device is
      involved, however, in >/=28% of these patients.

PMID- 11524398
TI  - Maternal energy stores and diet composition during pregnancy program adolescent
      blood pressure.
AB  - BACKGROUND: Fetal undernutrition is hypothesized to program blood pressure (BP)
      later in life. Human epidemiological studies that use birth weight as a proxy for
      fetal malnutrition fail to identify specific aspects of maternal nutrition
      responsible for programming. METHODS AND RESULTS: We examined how maternal
      nutrition during pregnancy and infant birth weight relate to systolic and
      diastolic BP (SBP and DBP) in 2026 Filipino adolescents. Data were collected
      prospectively during the Cebu (Philippines) Longitudinal Health and Nutrition
      Survey. Women were assessed at approximately 30 weeks gestation, and children
      were followed from birth through adolescence. Regression models were used to
      examine how the mothers' total energy intake, percentage of energy from protein
      and fat, triceps skinfold thickness during pregnancy, and infant birth weight
      relate to adolescent BP, controlling for current age, height, and body mass index
      and other potential confounders. Maternal triceps skinfold thickness was
      significantly inversely related to SBP among boys and to DBP in boys and girls.
      Maternal nutrition variables attenuated but did not eliminate an inverse birth
      weight-SBP relationship in boys. SBP was significantly inversely related to the
      mothers' percent of dietary energy from protein in boys. Among girls, SBP and DBP
      were inversely related to the mothers' percentage of calories from fat. There was
      no evidence of confounding of these relationships by current diet, maturation
      status, physical activity, or socioeconomic status. CONCLUSIONS: Maternal diet
      composition and energy stores in the form of subcutaneous fat have long-term
      effects on offspring BP in adolescence.

PMID- 11524399
TI  - Reduced sarco/endoplasmic reticulum Ca(2+) uptake activity can account for the
      reduced response to NO, but not sodium nitroprusside, in hypercholesterolemic
      rabbit aorta.
AB  - BACKGROUND: Hypercholesterolemia (HC) impairs acetylcholine-induced relaxation
      but has little effect on that caused by the NO donor sodium nitroprusside (SNP),
      suggesting that acetylcholine releases less NO from the endothelium in HC. The
      relaxation to authentic NO gas, however, is also impaired in HC aortic smooth
      muscle, indicating an abnormal smooth muscle response. NO relaxes arteries by
      both cGMP-dependent and -independent mechanisms, and the response involves
      calcium (Ca(2+)) store refilling via the sarco/endoplasmic reticulum calcium
      ATPase (SERCA). We studied the involvement of cGMP and SERCA in the smooth muscle
      response to NO and SNP in HC rabbit aorta. METHODS AND RESULTS: A selective
      guanylyl cyclase inhibitor, 1H-[1,2,4]-oxadiazole-[4,3-a]quinoxalin-1-one,
      eliminated SNP-induced relaxation but only partially blocked NO-induced
      relaxation in both normal and HC aorta. The residual relaxation to NO was still
      less in HC and, in both normal and HC aorta, was abolished by concomitant
      administration of the SERCA inhibitor cyclopiazonic acid (CPA). In contrast, CPA
      did not affect SNP-induced relaxation in either normal or HC aorta. SERCA
      activity measured by (45)Ca(2+) uptake was markedly decreased in HC, although
      SERCA2 protein expression did not change significantly. CONCLUSIONS: These data
      suggest that NO-induced relaxation but not that to SNP is partially mediated by
      cGMP-independent Ca(2+) uptake into sarco/endoplasmic reticulum and that reduced
      sarco/endoplasmic reticulum Ca(2+) pump function can account for the impaired
      response to NO in HC.

PMID- 11524400
TI  - Implantation of bone marrow mononuclear cells into ischemic myocardium enhances
      collateral perfusion and regional function via side supply of angioblasts,
      angiogenic ligands, and cytokines.
AB  - BACKGROUND: Bone marrow implantation (BMI) was shown to enhance angiogenesis in a
      rat ischemic heart model. This preclinical study using a swine model was designed
      to test the safety and therapeutic effectiveness of BMI. METHODS AND RESULTS: BM
      derived mononuclear cells (BM-MNCs) were injected into a zone made ischemic by
      coronary artery ligation. Three weeks after BMI, regional blood flow and
      capillary densities were significantly higher (4.6- and 2.8-fold, respectively),
      and cardiac function was improved. Angiography revealed that there was a marked
      increase (5.7-fold) in number of visible collateral vessels. Implantation of
      porcine coronary microvascular endothelial cells (CMECs) did not cause any
      significant increase in capillary densities. Labeled BM-MNCs were incorporated
      into approximately 31% of neocapillaries and corresponded to approximately 8.7%
      of macrophages but did not actively survive as myoblasts or fibroblasts. There
      was no bone formation by osteoblasts or malignant ventricular arrhythmia. Time
      dependent changes in plasma levels for cardiac enzymes (troponin I and creatine
      kinase-MB) did not differ between the BMI, CMEC, and medium-alone implantation
      groups. BM-MNCs contained 16% of endothelial-lineage cells and expressed basic
      fibroblast growth factor>>vascular endothelial growth factor>angiopoietin 1
      mRNAs, and their cardiac levels were significantly upregulated by BMI. Cardiac
      interleukin-1beta and tumor necrosis factor-alpha mRNA expression were also
      induced by BMI but not by CMEC implantation. BM-MNCs were actively differentiated
      to endothelial cells in vitro and formed network structure with human umbilical
      vein endothelial cells. CONCLUSIONS: BMI may constitute a novel safety strategy
      for achieving optimal therapeutic angiogenesis by the natural ability of the BM
      cells to secrete potent angiogenic ligands and cytokines as well as to be
      incorporated into foci of neovascularization.

PMID- 11524401
TI  - Ischemic preconditioning attenuates cardiac sympathetic nerve injury via ATP
      sensitive potassium channels during myocardial ischemia.
AB  - BACKGROUND: During myocardial ischemia, massive norepinephrine (NE) is released
      from the cardiac sympathetic nerve terminals, reflecting the sympathetic nerve
      injury. A brief preceding ischemia can reduce infarct size; this is known as
      ischemic preconditioning (PC). The effect of PC on sympathetic nerves, however,
      including its underlying mechanisms in dog hearts, has remained unclear. Thus,
      this study was designed to elucidate whether the activation of ATP-sensitive
      potassium (K(ATP)) channels is involved in the mechanism of cardiac sympathetic
      nerve protection conferred by PC. METHODS AND RESULTS: Interstitial NE
      concentration was measured by the in situ cardiac microdialysis method in 45
      anesthetized dogs. Five minutes of ischemia followed by 5 minutes of reperfusion
      was performed as PC. In the controls, the dialysate NE concentration (dNE)
      increased 15-fold after the 40-minute ischemia. PC decreased dNE at 40-minute
      ischemia by 59% (P<0.01), which was reversed by glibenclamide. A K(ATP) channel
      opener, nicorandil (25 microg. kg(-1). min(-1) IV), decreased dNE at 40 minutes
      of ischemia by 76% (P<0.01), which was also reversed by glibenclamide. During the
      PC procedure, no significant increase in dNE was detected, even with the uptake-1
      inhibitor desipramine. CONCLUSIONS: Cardiac sympathetic nerve injury during
      myocardial ischemia was attenuated by PC via the activation of K(ATP) channels,
      but the trigger of the PC effect is unlikely to be NE release in dog hearts.

PMID- 11524403
TI  - Right atrial septal electrode for reducing the atrial defibrillation threshold.
AB  - BACKGROUND: The atrial defibrillation threshold (ADFT) energy of the standard
      lead configuration, right atrial appendage (RAA) to coronary sinus (CS), was
      reduced by >50% with the addition of a third electrode traversing the atrial
      septum in a previous study. This study determined whether the ADFT would be
      lowered by a more clinically practical third electrode placed in the right atrium
      along the atrial septum (RSP). METHODS AND RESULTS: Sustained atrial fibrillation
      was induced in 8 closed-chest sheep with burst pacing and maintained with
      pericardial infusion of acetyl-beta-methylcholine chloride. A custom-made, dual
      defibrillation catheter was placed with electrodes in the lateral RA, CS, and
      RSP. A separate defibrillation catheter was also placed in the RAA. ADFT
      characteristics of RAA-->CS and 6 other single- or sequential-shock
      configurations were determined in random order by using biphasic, truncated
      exponential waveforms in a multiple-reversal protocol. The delivered-energy, peak
      voltage, and peak-current ADFTs for the sequential-shock configuration CS-
      >RSP/RA-->RSP (0.53+/-0.31 J, 86+/-22 V, and 1.6+/-0.6 A, respectively) were
      significantly lower than those of RAA-->CS (1.14+/-0.64 J, 157+/-34 V, and 2.5+/
      1.1 A, respectively). The ADFT characteristics of RAA-->CS and RA-->CS were not
      significantly different, nor were those of CS-->RSP/RA-->RSP and CS-->RSP/RAA-->
      RSP. CONCLUSIONS: The ADFT of the standard RAA-->CS configuration may be markedly
      reduced with an additional electrode situated at the RSP.

PMID- 11524402
TI  - Noninvasive quantification of the contractile reserve of stunned myocardium by
      ultrasonic strain rate and strain.
AB  - BACKGROUND: We sought to investigate ultrasonic strain rate and strain as new
      indices to quantify the contractile reserve of stunned myocardium during
      dobutamine infusion. METHODS AND RESULTS: Stunning of the left ventricular
      posterior wall was induced in 9 closed-chest pigs after 30 minutes of severe
      hypoperfusion followed by 60 minutes of reperfusion of the left circumflex
      coronary artery territory. A second group of 7 animals had no coronary occlusion
      and served as normal controls. An incremental dobutamine infusion protocol was
      used in both groups. Changes in regional radial function were monitored by use of
      ultrasound-derived maximal systolic radial strain rate (SR) and systolic strain
      (epsilon). In the control group, dobutamine induced an increase in both SR and
      maximal dP/dt, which correlated linearly (r=0.85). Conversely, epsilon values
      increased at low doses of dobutamine (2.5 to 5 microg. kg(-1). min(-1)) but
      decreased during higher infusion rates (10 to 20 microg. kg(-1). min(-1)). During
      circumflex hypoperfusion, SR and epsilon of the posterior wall decreased from
      5.0+/-0.3 s(-1) and 63+/-6% to 2.9+/-0.3 s(-1) and 27+/-4%, respectively
      (P<0.01). After 60 minutes of reperfusion, SR and epsilon failed to fully resume
      because of stunning, averaging 3.6+/-0.2 s(-1) and 35+/-3%, respectively (P=0.12
      versus ischemia, P<0.05 versus baseline). During dobutamine infusion, SR
      increased at 5 microg. kg(-1). min(-1) and exceeded baseline values at 20 microg.
      kg(-1). min(-1) (P<0.05), whereas epsilon increased only at high doses and
      remained below baseline levels (P<0.05). CONCLUSIONS: The changes in regional
      function of stunned myocardium during inotropic stimulation could be
      characterized by use of ultrasonic deformation parameters. During dobutamine
      infusion, strain-rate values quantified the contractile reserve better than
      strain values.

PMID- 11524404
TI  - Long-QT syndrome-associated missense mutations in the pore helix of the HERG
      potassium channel.
AB  - BACKGROUND: Mutations in the human ether-a-go-go-related gene (HERG) cause
      chromosome 7-linked long-QT syndrome (LQTS), an inherited disorder of cardiac
      repolarization that predisposes affected individuals to arrhythmia and sudden
      death. METHODS AND RESULTS: Here, we characterize the physiological consequences
      of 3 LQTS-associated missense mutations (V612L, T613M, and L615V) located in the
      pore helix of the HERG channel subunit. Mutant HERG subunits were heterologously
      expressed in Xenopus oocytes alone or in combination with wild-type HERG
      subunits. Two-microelectrode voltage-clamp techniques were used to record
      currents, and a single oocyte chemiluminescence assay was used to assay surface
      expression of epitope-tagged subunits. When expressed alone, V612L and T613M HERG
      subunits did not induce detectable currents, and L615V induced very small
      currents. Coexpression of mutant and wild-type HERG subunits caused a dominant
      negative effect that varied for each mutation. CONCLUSIONS: These findings define
      the physiological consequences of mutations in HERG that cause LQTS and indicate
      the importance of the pore helix of HERG for normal channel function.

PMID- 11524405
TI  - Advances in the understanding of myocarditis.

PMID- 11524406
TI  - Multislice spiral computed tomography of subacute myocardial infarction.

PMID- 11524407
TI  - Rapid development of a large systemic-to-pulmonary vein fistula after
      bidirectional Glenn shunt and successful closure with an Amplatzer duct occluder.

PMID- 11524408
TI  - Interpretation of trials on provisional stent implantation.

PMID- 11524409
TI  - Amiodarone in the new ACLS guidelines.

PMID- 11524410
TI  - 2000 Guidelines for Cardiopulmonary Resuscitation Emergency Cardiovascular Care.

PMID- 11524411
TI  - Role for complement as an intermediate between C-reactive protein and
      intercellular adhesion molecule-1 expression?

PMID- 11524412
TI  - Risk reduction and the program on the surgical control of the hyperlipidemias.

PMID- 11524413
TI  - Nitric oxide in vascular endothelial growth factor synthesis and signaling.

PMID- 11524414
TI  - Access of a membrane protein to secretory granules is facilitated by
      phosphorylation.
AB  - Peptidylglycine alpha-amidating monooxygenase (PAM), an integral membrane protein
      essential for the biosynthesis of amidated peptides, was used to assess the role
      of cytosolic acidic clusters in trafficking to regulated secretory granules.
      Casein kinase II phosphorylates Ser(949) and Thr(946) of PAM, generating a short,
      cytosolic acidic cluster. P-CIP2, a protein kinase identified by its ability to
      interact with several juxtamembrane determinants in the PAM cytosolic domain,
      also phosphorylates Ser(949). Antibody specific for phospho-Ser(949)-PAM-CD
      demonstrates that a small fraction of the PAM-1 localized to the perinuclear
      region bears this modification. Pituitary cell lines expressing PAM-1 mutants
      that mimic (TS/DD) or prevent (TS/AA) phosphorylation at these sites were
      studied. PAM-1 TS/AA yields a lumenal monooxygenase domain that enters secretory
      granules inefficiently and is rapidly degraded. In contrast, PAM-1 TS/DD is
      routed to regulated secretory granules more efficiently than wild-type PAM-1 and
      monooxygenase release is more responsive to secretagogue. Furthermore, this
      acidic cluster affects exit of internalized PAM-antibody complexes from late
      endosomes; internalized PAM-1 TS/DD accumulates in a late endocytic compartment
      instead of the trans-Golgi network. The increased ability of solubilized PAM-1
      TS/DD to aggregate at neutral pH may play an important role in its altered
      trafficking.

PMID- 11524415
TI  - Calcium-sensitive regions of GCAP1 as observed by chemical modifications,
      fluorescence, and EPR spectroscopies.
AB  - Guanylyl cyclase-activating proteins are EF-hand Ca(2+)-binding proteins that
      belong to the calmodulin superfamily. They are involved in the regulation of
      photoreceptor membrane-associated guanylyl cyclases that produce cGMP, a second
      messenger of vertebrate vision. Here, we investigated changes in GCAP1 structure
      using mutagenesis, chemical modifications, and spectroscopic methods. Two Cys
      residues of GCAP1 situated in spatially distinct regions of the N-terminal domain
      (positions 18 and 29) and two Cys residues located within the C-terminal lobe
      (positions 106 and 125) were employed to detect conformational changes upon
      Ca(2+) binding. GCAP1 mutants with only a single Cys residue at each of these
      positions, modified with N,N'-dimethyl-N-(iodoacetyl)-N'-(7-nitrobenz-2-oxa-1,3
      diazol-4-yl)ethylenediamine, an environmentally sensitive fluorophore, and with
      (1-oxy-2,2,5,5-tetramethylpyrroline-3-methyl)methanethiosulfonate, a spin label
      reagent, were studied using fluorescence and EPR spectroscopy, respectively. Only
      minor structural changes around Cys(18), Cys(29), Cys(106), and Cys(125) were
      observed as a function of Ca(2+) concentration. No Ca(2+)-dependent
      oligomerization of GCAP1 was observed at physiologically relevant Ca(2+)
      concentrations, in contrast to the observation reported by others for GCAP2.
      Based on these results and previous studies, we propose a photoreceptor
      activation model that assumes changes within the flexible central helix upon
      Ca(2+) dissociation, causing relative reorientation of two structural domains
      containing a pair of EF-hand motifs and thus switching its partner, guanylyl
      cyclase, from an inactive (or low activity) to an active conformation.

PMID- 11524416
TI  - Demethylase activity is directed by histone acetylation.
AB  - Mammalian genomes are compartmentalized into dense inactive chromatin that is
      hypermethylated and active open chromatin that is hypomethylated. It is generally
      accepted that this bimodal pattern of methylation is established during
      development and is then faithfully inherited through subsequent cell divisions by
      a maintenance DNA methyltransferase (DNMT1). The pattern of methylation is
      believed to direct local histone acetylation states. In contrast to this well
      accepted consensus, we show here using a transient transfection model that an
      active demethylase is involved in shaping patterns of methylation in somatic
      cells. Demethylase activity is directed by the state of histone acetylation, and
      therefore, the resulting methylation pattern is determined by local histone
      acetylation states contrary to the accepted model. Our data support a new model
      suggesting that the pattern of methylation is maintained by a dynamic balance of
      methylation and demethylation activities and the local state of histone
      acetylation. This provides a simple mechanism for explaining why active genes are
      not methylated.

PMID- 11524417
TI  - Crystal structure and substrate binding modeling of the uroporphyrinogen-III
      decarboxylase from Nicotiana tabacum. Implications for the catalytic mechanism.
AB  - The enzymatic catalysis of many biological processes of life is supported by the
      presence of cofactors and prosthetic groups originating from the common
      tetrapyrrole precursor uroporphyrinogen-III. Uroporphyrinogen-III decarboxylase
      catalyzes its conversion into coproporphyrinogen-III, leading in plants to
      chlorophyll and heme biosynthesis. Here we report the first crystal structure of
      a plant (Nicotiana tabacum) uroporphyrinogen-III decarboxylase, together with the
      molecular modeling of substrate binding in tobacco and human enzymes. Its
      structural comparison with the homologous human protein reveals a similar
      catalytic cleft with six invariant polar residues, Arg(32), Arg(36), Asp(82),
      Ser(214) (Thr in Escherichia coli), Tyr(159), and His(329) (tobacco numbering).
      The functional relationships obtained from the structural and modeling analyses
      of both enzymes allowed the proposal for a refined catalytic mechanism. Asp(82)
      and Tyr(159) seem to be the catalytic functional groups, whereas the other
      residues may serve in substrate recognition and binding, with Arg(32) steering
      its insertion. The crystallographic dimer appears to represent the protein dimer
      under physiological conditions. The dimeric arrangement offers a plausible
      mechanism at least for the first two (out of four) decarboxylation steps.

PMID- 11524418
TI  - Contribution of extracellular Glu residues to the structure and function of
      bacteriorhodopsin. Presence of specific cation-binding sites.
AB  - Single and multiple mutants of extracellular Glu side chains of bacteriorhodopsin
      were analyzed by acid and calcium titration, differential scanning calorimetry,
      and thermal difference spectrophotometry. Acid titration spectra show that the
      second group protonating with Asp(85) is revealed in E204Q in the absence of Cl(
      ) but is not observed in the triple mutant E9Q/E194Q/E204Q or in the quadruple
      mutant E9Q/E74Q/E194Q/E204Q. The results point to Glu(9) as the second group
      protonating cooperatively with Asp(85). Comparison of the apparent pK(a) of
      Asp(85) protonation in water and in the deionized forms and results of calcium
      titration suggest that cation-binding sites are of low affinity in the multiple
      Glu mutants. Like for deionized wild type bacteriorhodopsin, differential
      scanning calorimetry reveals a lack of the pretransition in the multiple mutants,
      whereas in E9Q it appears at lower temperature and with lower cooperativity.
      Additionally, at neutral pH the band at 630 nm arising from cation release upon
      temperature increase is absent for the multiple mutants. Based on these results,
      we propose the presence of two cation-binding sites in the extracellular region
      of bacteriorhodopsin having as ligands Glu(9), Glu(194), Glu(204), and water
      molecules.

PMID- 11524419
TI  - Antioxidative function and substrate specificity of NAD(P)H-dependent alkenal/one
      oxidoreductase. A new role for leukotriene B4 12-hydroxydehydrogenase/15
      oxoprostaglandin 13-reductase.
AB  - There are several known routes for the metabolic detoxication of alpha,beta
      unsaturated aldehydes and ketones, including conjugation to glutathione and
      reduction and oxidation of the aldehyde to an alcohol and a carboxylic acid,
      respectively. In this study, we describe a fourth class of detoxication that
      involves the reduction of the alpha,beta-carbon=carbon double bond to a single
      bond. This reaction is catalyzed by NAD(P)H-dependent alkenal/one oxidoreductase
      (AO), an enzyme heretofore known as leukotriene B4 12-hydroxydehydrogenase, 15
      oxoprostaglandin 13-reductase, and dithiolethione-inducible gene-1. AO is shown
      to effectively reduce cytotoxic lipid peroxidation products such as 4-hydroxy-2
      nonenal (HNE) (k(cat) = 4.0 x 10(3) min(-1); k(cat)/K(m) = 3.3 x 10(7) min(-1) M(
      1)) and acrolein (k(cat) = 2.2 x 10(2) min(-1); k(cat)/K(m) = 1.5 x 10(6) min(-1)
      M(-1)) and common industrial compounds such as ethyl vinyl ketone (k(cat) = 9.6 x
      10(3) min(-1); k(cat)/K(m) = 8.8 x 10(7) min(-1) M(-1)) and 15-oxoprostaglandin
      E1 (k(cat) = 2.4 x 10(3) min(-1); k(cat)/K(m) = 2.4 x 10(9) min(-1) M(-1)).
      Furthermore, transfection of human embryonic kidney cells with a rat liver AO
      expression vector protected these cells from challenge with HNE. The
      concentration of HNE at which 50% of the cells were killed after 24 h increased
      from approximately 15 microM in control cells to approximately 70 microM in AO
      transfected cells. Overexpression of AO also completely abolished protein
      alkylation by HNE at all concentrations tested (up to 30 microM). Thus, we
      describe a novel antioxidative activity of a previously characterized bioactive
      lipid-metabolizing enzyme that could prove to be therapeutically or
      prophylactically useful due to its high catalytic rate and inducibility.

PMID- 11524421
TI  - Identification and characterization of RA-GEF-2, a Rap guanine nucleotide
      exchange factor that serves as a downstream target of M-Ras.
AB  - The Ras family small GTPase Rap is regulated by an array of specific guanine
      nucleotide exchange factors (GEFs) in response to upstream stimuli. RA-GEF-1 was
      identified as a novel Rap GEF, which possesses a Ras/Rap1-associating (RA)
      domain. Here we report a protein closely related to RA-GEF-1, named RA-GEF-2.
      Like RA-GEF-1, a putative cyclic nucleotide monophosphate-binding domain, a Ras
      exchanger motif, a PSD-95/DlgA/ZO-1 domain, and an RA domain in addition to the
      GEF catalytic domain are found in RA-GEF-2. However, RA-GEF-2 displays a
      different tissue distribution profile from that of RA-GEF-1. RA-GEF-2 stimulates
      guanine nucleotide exchange of both Rap1 and Rap2, but not Ha-Ras. The RA domain
      of RA-GEF-2 binds to M-Ras in a GTP-dependent manner, but not to other Ras family
      GTPases tested, including Ha-Ras, N-Ras, Rap1A, Rap2A, R-Ras, RalA, Rin, Rit, and
      Rheb, in contrast to the RA domain of RA-GEF-1, which specifically binds to Rap1.
      In accordance with this, RA-GEF-2 colocalizes with activated M-Ras in the plasma
      membrane in COS-7 cells, suggesting a role of RA-GEF-2 in the regulation of Rap1
      and Rap2, particularly in the plasma membrane. In fact, an increase in the level
      of the GTP-bound form of plasma membrane-located Rap1 was observed when
      coexpressed with RA-GEF-2 and activated M-Ras. Thus, RA-GEF-2 acts as a GEF for
      Rap1 and Rap2 downstream of M-Ras in the plasma membrane, whereas RA-GEF-1 exerts
      Rap GEF function in perinuclear compartments including the Golgi apparatus.

PMID- 11524420
TI  - Different subtypes of alpha1-adrenoceptor modulate different K+ currents via
      different signaling pathways in canine ventricular myocytes.
AB  - Multiple subtypes (alpha1A, alpha1B, and alpha1D) of alpha1-adrenoreceptors
      (alpha1ARs) co-exist in the heart and mediate a variety of cellular functions. We
      studied alphaAR modulation of inward rectifier (IK1) and transient outward (Ito)
      K(+) currents in canine ventricular myocytes. Phenylephrine at 10 microM
      depressed only Ito without affecting IK1 and at 100 microM inhibited both Ito and
      IK1. The effect of phenylephrine on Ito was abolished by (+)niguldipine (10 nm)
      to inhibit alpha1AARs but not by chloroethyclonidine (10 microM) to inactivate
      alpha1BARs nor by BMY-7378 to antagonize alpha1DARs. In contrast, phenylephrine
      inhibition of IK1 was reversed only by BMY-7378 (1 nm). PDD (100 nm, phorbol
      ester activator of protein kinase C (PKC)) simulates and bisindolylmaleimide (50
      nm, PKC inhibitor) weakens phenylephrine modulation of Ito but not IK1.
      Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) inhibitor KN-93 and
      inhibitor peptides abolished the effects of phenylephrine on IK1. Enhancement of
      PKC or CaMKII activities was seen in alpha1aAR- or alpha1dAR-transfected HEK293
      cells and in myocytes pretreated with 10 or 100 microM phenylephrine,
      respectively. Our data suggest that different subtypes of alpha1ARs selectively
      modulate different cardiac K(+) currents via different signal transduction
      mechanisms; alpha1AARs mediate Ito regulation via PKC, and alpha1DARs mediate IK1
      regulation via CaMKII.

PMID- 11524422
TI  - The complete pathway for catalytic activation of the mitogen-activated protein
      kinase, ERK2.
AB  - The mitogen-activated protein (MAP) kinase ERK2 is an essential signal
      transduction molecule that mediates extracellular signaling by all polypeptide
      growth factors. Full activation of ERK2 requires phosphorylation at both a
      threonine residue (Thr(183)) conserved in most protein kinases as well as a
      tyrosine residue (Tyr(185)) unique to members of the mitogen-activated protein
      kinase family. We have characterized the kinetic role of phosphorylation at each
      site with respect to the overall activation mechanism, providing a complete
      picture of the reaction steps involved. Phosphorylation at Tyr(185) serves to
      configure the ATP binding site, while phosphorylation at both residues is
      required to stabilize binding of the protein substrate, myelin basic protein.
      Similar control mechanisms are employed to stabilize ATP and myelin basic protein
      in the phosphoryl group transfer reaction, accounting for the enormous increase
      in turnover rate. The mechanism of ERK2 activation is kinetically similar to that
      of the cell cycle control protein, cdk2/cyclinA. Phosphorylation of Tyr(185) in
      ERK2 and association of cyclinA with cdk2 both serve to stabilize ATP binding.
      Subsequent phosphorylation of both enzymes on threonine serves to stabilize
      binding of the phosphoacceptor substrate.

PMID- 11524423
TI  - Spring, a novel RING finger protein that regulates synaptic vesicle exocytosis.
AB  - The synaptosome-associated protein of 25 kDa (SNAP-25) interacts with syntaxin 1
      and vesicle-associated membrane protein 2 (VAMP2) to form a ternary soluble N
      ethylmaleimide-sensitive fusion protein attachment protein receptor (SNARE)
      complex that is essential for synaptic vesicle exocytosis. We report a novel RING
      finger protein, Spring, that specifically interacts with SNAP-25. Spring is
      exclusively expressed in brain and is concentrated at synapses. The association
      of Spring with SNAP-25 abolishes the ability of SNAP-25 to interact with syntaxin
      1 and VAMP2 and prevents the assembly of the SNARE complex. Overexpression of
      Spring or its SNAP-25-interacting domain reduces Ca(2+)-dependent exocytosis from
      PC12 cells. These results indicate that Spring may act as a regulator of synaptic
      vesicle exocytosis by controlling the availability of SNAP-25 for the SNARE
      complex formation.

PMID- 11524424
TI  - Analysis of allosteric effector binding sites of potato ADP-glucose
      pyrophosphorylase through reverse genetics.
AB  - ADP-glucose pyrophosphorylase (AGPase) is a key regulatory enzyme of bacterial
      glycogen and plant starch synthesis as it controls carbon flux via its allosteric
      regulatory behavior. Unlike the bacterial enzyme that is composed of a single
      subunit type, the plant AGPase is a heterotetrameric enzyme (alpha2beta2) with
      distinct roles for each subunit type. The large subunit (LS) is involved mainly
      in allosteric regulation through its interaction with the catalytic small subunit
      (SS). The LS modulates the catalytic activity of the SS by increasing the
      allosteric regulatory response of the hetero-oligomeric enzyme. To identify
      regions of the LS involved in binding of effector molecules, a reverse genetics
      approach was employed. A potato (Solanum tuberosum L.) AGPase LS down-regulatory
      mutant (E38A) was subjected to random mutagenesis using error-prone polymerase
      chain reaction and screened for the capacity to form an enzyme capable of
      restoring glycogen production in glgC(-) Escherichia coli. Dominant mutations
      were identified by their capacity to restore glycogen production when the LS
      containing only the second site mutations was co-expressed with the wild-type SS.
      Sequence analysis showed that most of the mutations were decidedly nonrandom and
      were clustered at conserved N- and C-terminal regions. Kinetic analysis of the
      dominant mutant enzymes indicated that the K(m) values for cofactor and
      substrates were comparable with the wild-type AGPase, whereas the affinities for
      activator and inhibitor were altered appreciably. These AGPase variants displayed
      increased resistance to P(i) inhibition and/or greater sensitivity toward 3
      phosphoglyceric acid activation. Further studies of Lys-197, Pro-261, and Lys
      420, residues conserved in AGPase sequences, by site-directed mutagenesis
      suggested that the effectors 3-phosphoglyceric acid and P(i) interact at two
      closely located binding sites.

PMID- 11524425
TI  - Exocytosis of catecholamine (CA)-containing and CA-free granules in chromaffin
      cells.
AB  - Recent evidence suggests that endocytosis in neuroendocrine cells and neurons can
      be tightly coupled to exocytosis, allowing rapid retrieval from the plasma
      membrane of fused vesicles for future use. This can be a much faster mechanism
      for membrane recycling than classical clathrin-mediated endocytosis. During a
      fast exo-endocytotic cycle, the vesicle membrane does not fully collapse into the
      plasma membrane; nevertheless, it releases the vesicular contents through the
      fusion pore. Once the vesicle is depleted of transmitter, its membrane is
      recovered without renouncing its identity. In this report, we show that
      chromaffin cells contain catecholamine-free granules that retain their ability to
      fuse with the plasma membrane. These catecholamine-free granules represent 7% of
      the total population of fused vesicles, but they contributed to 47% of the fusion
      events when the cells were treated with reserpine for several hours. We propose
      that rat chromaffin granules that transiently fuse with the plasma membrane
      preserve their exocytotic machinery, allowing another round of exocytosis.

PMID- 11524426
TI  - Typical demethylation events in cloned pig embryos. Clues on species-specific
      differences in epigenetic reprogramming of a cloned donor genome.
AB  - We investigated whether a genomic demethylation process occurs in pig
      preimplantation embryos produced by either normal fertilization or somatic cell
      nuclear transfer. The methylation status of the centromeric satellite and the PRE
      1 short interspersed element (SINE) sequences was characterized using bisulfite
      sequencing technology. Typical demethylation processes were identified in these
      repetitive sequences of the cloned donor genome during cleavage, the patterns of
      which were similar to the ones detected in fertilized counterparts. These
      findings are different from previous observations with cloned bovine embryos
      where various repeated regions of the donor genome exhibited aberrant methylation
      patterns. Our results indicate that species-specific differences exist in
      modifying the epigenetic status of cloned donor genomes.

PMID- 11524427
TI  - Conformational heterogeneity in the C-terminal zinc fingers of human MTF-1: an
      NMR and zinc-binding study.
AB  - The human metalloregulatory transcription factor, metal-response element (MRE)
      binding transcription factor-1 (MTF-1), contains six TFIIIA-type Cys(2)-His(2)
      motifs, each of which was projected to form well-structured betabetaalpha domains
      upon Zn(II) binding. In this report, the structure and backbone dynamics of a
      fragment containing the unusual C-terminal fingers F4-F6 has been investigated.
      (15)N heteronuclear single quantum coherence (HSQC) spectra of uniformly (15)N
      labeled hMTF-zf46 show that Zn(II) induces the folding of hMTF-zf46. Analysis of
      the secondary structure of Zn(3) hMTF-zf46 determined by (13)Calpha chemical
      shift indexing and the magnitude of (3)J(Halpha-HN) clearly reveal that zinc
      fingers F4 and F6 adopt typical betabetaalpha structures. An analysis of the
      heteronuclear backbone (15)N relaxation dynamics behavior is consistent with this
      picture and further reveals independent tumbling of the finger domains in
      solution. Titration of apo-MTF-zf46 with Zn(II) reveals that the F4 domain binds
      Zn(II) significantly more tightly than do the other two finger domains. In
      contrast to fingers F4 and F6, the betabetaalpha fold of finger F5 is unstable
      and only partially populated at substoichiometric Zn(II); a slight molar excess
      of zinc results in severe conformational exchange broadening of all F5 NH cross
      peaks. Finally, although Cd(II) binds to apo-hMTF-zf46 as revealed by intense S(
      )-->Cd(II) absorption, a non-native structure results; addition of stoichiometric
      Zn(II) to the Cd(II) complex results in quantitative refolding of the
      betabetaalpha structure in F4 and F6. The functional implications of these
      results are discussed.

PMID- 11524428
TI  - Distinct Albino3-dependent and -independent pathways for thylakoid membrane
      protein insertion.
AB  - The homologous proteins Oxa1, YidC, and Alb3 mediate the insertion of membrane
      proteins in mitochondria, bacteria, and chloroplast thylakoids, respectively.
      Depletion of YidC in Escherichia coli affects the integration of every membrane
      protein studied, and Alb3 has been shown previously to be required for the
      insertion of a signal recognition particle (SRP)-dependent protein, Lhcb1, in
      thylakoids. In this study we have analyzed the "global" role of Alb3 in the
      insertion of thylakoid membrane proteins. We show that insertion of two
      chlorophyll-binding proteins, Lhcb4.1 and Lhcb5, is almost totally blocked by
      preincubation of thylakoids with anti-Alb3 antibodies, indicating a requirement
      for Alb3 in the insertion pathway. Insertion of the related PsbS protein, on the
      other hand, is unaffected by Alb3 antibodies, and insertion of a group of SRP
      independent, signal peptide-bearing proteins, PsbX, PsbW, and PsbY, is likewise
      completely unaffected. Proteinase K is furthermore able to completely degrade
      Alb3, but this treatment does not affect the insertion of these proteins. Among
      the thylakoid proteins studied here, Alb3 requirement correlates strictly with a
      requirement for stromal factors and nucleoside triphosphates. However, the
      majority of proteins tested do not require Alb3 or any other known form of
      translocation apparatus.

PMID- 11524429
TI  - Stabilization of cortical actin induces internalization of transient receptor
      potential 3 (Trp3)-associated caveolar Ca2+ signaling complex and loss of Ca2+
      influx without disruption of Trp3-inositol trisphosphate receptor association.
AB  - Ca(2+) influx via plasma membrane Trp3 channels is proposed to be regulated by a
      reversible interaction with inositol trisphosphate receptor (IP(3)R) in the
      endoplasmic reticulum. Condensation of the cortical actin layer has been
      suggested to physically disrupt this interaction and inhibit Trp3-mediated Ca(2+)
      influx. This study examines the effect of cytoskeletal reorganization on the
      localization and function of Trp3 and key Ca(2+) signaling proteins. Calyculin-A
      treatment resulted in formation of condensed actin layer at the plasma membrane;
      internalization of Trp3, Galpha(q/11), phospholipase Cbeta, and caveolin-1; and
      attenuation of 1-oleoyl-2-acetyl-sn-glycerol- and ATP-stimulated Sr(2+) influx.
      Importantly, Trp3 and IP(3)R-3 remained co-localized inside the cell and were co
      immunoprecipitated. Jasplakinolide also induced internalization of Trp3 and
      caveolin-1. Pretreatment of cells with cytochalasin D or staurosporine did not
      affect Trp3 but prevented calyculin-A-induced effects. Based on these data, we
      suggest that Trp3 is assembled in a caveolar Ca(2+) signaling complex with
      IP(3)R, SERCA, Galpha(q/11), phospholipase Cbeta, caveolin-1, and ezrin.
      Furthermore, our data demonstrate that conditions which stabilize cortical actin
      induce loss of Trp3 activity due to internalization of the Trp3-signaling
      complex, not disruption of IP(3)R-Trp3 interaction. This suggests that
      localization of the Trp3-associated signaling complex, rather than Trp3-IP(3)R
      coupling, depends on the status of the actin cytoskeleton.

PMID- 11524430
TI  - Src family kinases mediate receptor-stimulated, phosphoinositide 3-kinase
      dependent, tyrosine phosphorylation of dual adaptor for phosphotyrosine and 3
      phosphoinositides-1 in endothelial and B cell lines.
AB  - DAPP-1 (dual-adaptor for phosphotyrosine and 3-phosphoinositides-1) is a broadly
      distributed pleckstrin homology (PH) and Src homology 2 domain containing protein
      that can bind phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P(3)) and
      can be phosphorylated on tyrosine 139 and internalised in response to activation
      of type I phosphoinositide 3-kinases (PI3K). Tyrosine phosphorylation of DAPP-1
      appears important for appropriate intracellular targeting and creates a potential
      binding site for Src homology 2 domain-containing proteins. In endothelial cells
      overexpressing wild-type platelet-derived growth factor beta (PDGFbeta)
      receptors, which express Bmx and Src as their major Btk (Bruton's tyrosine
      kinase) family and Src family tyrosine kinases, respectively, PDGF can stimulate
      PI3K-dependent tyrosine phosphorylation of DAPP-1. Transient overexpression of
      Src most effectively, compared with Bmx and Syk, augments basal and PDGF
      stimulated tyrosine phosphorylation of DAPP-1, whereas overexpression of dominant
      negative Src, but not dominant-negative Bmx, inhibits PDGF-stimulated
      phosphorylation of DAPP-1. Cells expressing mutant PDGFbeta (Y579F/Y581F)
      receptors (which fail to bind and activate Src-type kinases) fail to tyrosine
      phosphorylate DAPP-1 in response to PDGF. We show that in DT40 chicken B cell
      lines, antibody stimulation leads to PI3K-dependent tyrosine phosphorylation of
      DAPP-1 that is lost in Lyn- or Syk-deficient cell lines but not Btk-deficient
      cell lines. PI3K-dependent activation of PKB is only lost in Syk-deficient lines.
      Finally, in vitro we find lipid-modified Src to be the most effective DAPP-1
      tyrosine kinase (versus Syk, Lyn, Btk, and Bmx); phosphorylation of DAPP-1 but
      not Src autophosphorylation is stimulated approximately 10-fold by
      PtdIns(3,4,5)P(3) (IC(50) = 150 nm) and phosphatidylinositol 3,4-bisphosphate but
      not by their nonbiological diastereoisomers and depends on PH domain mediated
      binding of DAPP-1 to PtdIns(3,4,5)P(3)-containing membranes. We conclude that Src
      family kinases are responsible for tyrosine phosphorylation of DAPP-1 in vivo and
      that PI3K regulation is at the level of PH domain-mediated translocation of DAPP
      1 to PI3K products in the membrane.

PMID- 11524431
TI  - TNFalpha and oxLDL reduce protein S-nitrosylation in endothelial cells.
AB  - Nitric oxide (NO) plays an important role in the regulation of the functional
      integrity of the endothelium. The intracellular reaction of NO with reactive
      cysteine groups leads to the formation of S-nitrosothiols. To investigate the
      regulation of S-nitrosothiols in endothelial cells, we first analyzed the
      composition of the S-nitrosylated molecules in endothelial cells. Gel filtration
      revealed that more than 95% of the detected S-nitrosothiols had a molecular mass
      of more than 5000 Da. Moreover, inhibition of de novo synthesis of glutathione
      using N-butyl-sulfoximine did not diminish the overall cellular S-NO content
      suggesting that S-nitrosylated glutathione quantitatively plays only a minor role
      in endothelial cells. Having demonstrated that most of the S-nitrosothiols are
      proteins, we determined the regulation of the S-nitrosylation by pro-inflammatory
      and pro-atherogenic factors, such as TNFalpha and mildly oxidized low density
      lipoprotein (oxLDL). TNFalpha and oxLDL induced denitrosylation of various
      proteins as assessed by Saville-Griess assay, by immunostaining with an anti-S
      nitrosocysteine antibody, and by a Western blot approach. Furthermore, the
      caspase-3 p17 subunit, which has previously been shown to be S-nitrosylated and
      thereby inhibited, was denitrosylated by TNFalpha treatment suggesting that S
      nitrosylation and denitrosylation are important regulatory mechanisms in
      endothelial cells contributing to the integrity of the endothelial cell
      monolayer.

PMID- 11524432
TI  - Modification of epidermal growth factor-like repeats with O-fucose. Molecular
      cloning and expression of a novel GDP-fucose protein O-fucosyltransferase.
AB  - The O-fucose modification is found on epidermal growth factor-like repeats of a
      number of cell surface and secreted proteins. O-Fucose glycans play important
      roles in ligand-induced receptor signaling. For example, elongation of O-fucose
      on Notch by the beta1,3-N-acetylglucosaminyltransferase Fringe modulates the
      ability of Notch to respond to its ligands. The enzyme that adds O-fucose to
      epidermal growth factor-like repeats, GDP-fucose protein O-fucosyltransferase (O
      FucT-1), was purified previously from Chinese hamster ovary (CHO) cells. Here we
      report the isolation of a cDNA that encodes human O-FucT-1. A probe deduced from
      N-terminal sequence analysis of purified CHO O-FucT-1 was used to screen a human
      heart cDNA library and expressed sequence tag and genomic data bases. The cDNA
      contains an open reading frame encoding a protein of 388 amino acids with a
      predicted N-terminal transmembrane sequence typical of a type II membrane
      orientation. Likewise, the mouse homolog obtained from an expressed sequence tag
      and 5'-rapid amplification of cDNA ends of a mouse liver cDNA library encodes a
      type II transmembrane protein of 393 amino acids with 90.4% identity to human O
      FucT-1. Homologs were also found in Drosophila and Caenorhabditis elegans with
      41.2 and 29.4% identity to human O-FucT-1, respectively. The human gene (POFUT1)
      is on chromosome 20 between PLAGL2 and KIF3B, near the centromere at 20p11. The
      mouse gene (Pofut1) maps near Plagl2 on a homologous region of mouse chromosome
      2. POFUT1 gene transcripts were expressed in all tissues examined, consistent
      with the widespread localization of the modification. Expression of a soluble
      form of human O-FucT-1 in insect cells yielded a protein of the predicted
      molecular weight with O-FucT-1 kinetic and enzymatic properties similar to those
      of O-FucT-1 purified from CHO cells. The identification of the gene encoding
      protein O-fucosyltransferase I now makes possible mutational strategies to
      examine the functions of the unusual O-fucose post-translational modification.

PMID- 11524433
TI  - Role of PI 3-kinase, Akt and Bcl-2-related proteins in sustaining the survival of
      neurotrophic factor-independent adult sympathetic neurons.
AB  - By adulthood, sympathetic neurons have lost dependence on NGF and NT-3 and are
      able to survive in culture without added neurotrophic factors. To understand the
      molecular mechanisms that sustain adult neurons, we established low density,
      glial cell-free cultures of 12-wk rat superior cervical ganglion neurons and
      manipulated the function and/or expression of key proteins implicated in
      regulating cell survival. Pharmacological inhibition of PI 3-kinase with LY294002
      or Wortmannin killed these neurons, as did dominant-negative Class IA PI 3
      kinase, overexpression of Rukl (a natural inhibitor of Class IA PI 3-kinase), and
      dominant-negative Akt/PKB (a downstream effector of PI 3-kinase). Phospho-Akt was
      detectable in adult sympathetic neurons grown without neurotrophic factors and
      this was lost upon PI 3-kinase inhibition. The neurons died by a caspase
      dependent mechanism after inhibition of PI 3-kinase, and were also killed by
      antisense Bcl-xL and antisense Bcl-2 or by overexpression of Bcl-xS, Bad, and
      Bax. These results demonstrate that PI 3-kinase/Akt signaling and the expression
      of antiapoptotic members of the Bcl-2 family are required to sustain the survival
      of adult sympathetic neurons.

PMID- 11524435
TI  - Physiological regulation of [beta]-catenin stability by Tcf3 and CK1epsilon.
AB  - The wnt pathway regulates the steady state level of beta-catenin, a
      transcriptional coactivator for the Tcf3/Lef1 family of DNA binding proteins. We
      demonstrate that Tcf3 can inhibit beta-catenin turnover via its competition with
      axin and adenomatous polyposis for beta-catenin binding. A mutant of beta-catenin
      that cannot bind Tcf3 is degraded faster than the wild-type protein in Xenopus
      embryos and extracts. A fragment of beta-catenin and a peptide encoding the NH2
      terminus of Tcf4 that block the interaction between beta-catenin and Tcf3
      stimulate beta-catenin degradation, indicating this interaction normally plays an
      important role in regulating beta-catenin turnover. Tcf3 is a substrate for both
      glycogen synthase kinase (GSK) 3 and casein kinase (CK) 1epsilon, and
      phosphorylation of Tcf3 by CKIepsilon stimulates its binding to beta-catenin, an
      effect reversed by GSK3. Tcf3 synergizes with CK1epsilon to inhibit beta-catenin
      degradation, whereas CKI-7, an inhibitor of CK1epsilon, reduces the inhibitory
      effect of Tcf3. Finally, we provide evidence that CK1epsilon stimulates the
      binding of dishevelled (dsh) to GSk3 binding protein (GBP) in extracts. Along
      with evidence that a significant amount of Tcf protein is nonnuclear, these
      findings suggest that CK1epsilon can modulate wnt signaling in vivo by regulating
      both the beta-catenin-Tcf3 and the GBP-dsh interfaces.

PMID- 11524434
TI  - Functional specialization of calreticulin domains.
AB  - Calreticulin is a Ca2+-binding chaperone in the endoplasmic reticulum (ER), and
      calreticulin gene knockout is embryonic lethal. Here, we used calreticulin
      deficient mouse embryonic fibroblasts to examine the function of calreticulin as
      a regulator of Ca2+ homeostasis. In cells without calreticulin, the ER has a
      lower capacity for Ca2+ storage, although the free ER luminal Ca2+ concentration
      is unchanged. Calreticulin-deficient cells show inhibited Ca2+ release in
      response to bradykinin, yet they release Ca2+ upon direct activation with the
      inositol 1,4,5-trisphosphate (InsP3). These cells fail to produce a measurable
      level of InsP3 upon stimulation with bradykinin, likely because the binding of
      bradykinin to its cell surface receptor is impaired. Bradykinin binding and
      bradykinin-induced Ca2+ release are both restored by expression of full-length
      calreticulin and the N + P domain of the protein. Expression of the P + C domain
      of calreticulin does not affect bradykinin-induced Ca2+ release but restores the
      ER Ca2+ storage capacity. Our results indicate that calreticulin may play a role
      in folding of the bradykinin receptor, which affects its ability to initiate
      InsP3-dependent Ca2+ release in calreticulin-deficient cells. We concluded that
      the C domain of calreticulin plays a role in Ca2+ storage and that the N domain
      may participate in its chaperone functions.

PMID- 11524437
TI  - Cotyledon cells of Vigna mungo seedlings use at least two distinct autophagic
      machineries for degradation of starch granules and cellular components.
AB  - alpha-Amylase is expressed in cotyledons of germinated Vigna mungo seeds and is
      responsible for the degradation of starch that is stored in the starch granule
      (SG). Immunocytochemical analysis of the cotyledon cells with anti-alpha-amylase
      antibody showed that alpha-amylase is transported to protein storage vacuole
      (PSV) and lytic vacuole (LV), which is converted from PSV by hydrolysis of
      storage proteins. To observe the insertion/degradation processes of SG into/in
      the inside of vacuoles, ultrastructural analyses of the cotyledon cells were
      conducted. The results revealed that SG is inserted into LV through autophagic
      function of LV and subsequently degraded by vacuolar alpha-amylase. The autophagy
      for SG was structurally similar to micropexophagy detected in yeast cells. In
      addition to the autophagic process for SG, autophagosome-mediated autophagy for
      cytoplasm and mitochondria was detected in the cotyledon cells. When the embryo
      axes were removed from seeds and the detached cotyledons were incubated, the
      autophagosome-mediated autophagy was observed, but the autophagic process for the
      degradation of SG was not detected, suggesting that these two autophagic
      processes were mediated by different cellular mechanisms. The two distinct
      autophagic processes were thought to be involved in the breakdown of SG and cell
      components in the cells of germinated cotyledon.

PMID- 11524436
TI  - An effector region in Eps8 is responsible for the activation of the Rac-specific
      GEF activity of Sos-1 and for the proper localization of the Rac-based actin
      polymerizing machine.
AB  - Genetic and biochemical evidence demonstrated that Eps8 is involved in the
      routing of signals from Ras to Rac. This is achieved through the formation of a
      tricomplex consisting of Eps8-E3b1-Sos-1, which is endowed with Rac guanine
      nucleotide exchange activity. The catalytic subunit of this complex is
      represented by Sos-1, a bifunctional molecule capable of catalyzing guanine
      nucleotide exchange on Ras and Rac. The mechanism by which Sos-1 activity is
      specifically directed toward Rac remains to be established. Here, by performing a
      structure-function analysis we show that the Eps8 output function resides in an
      effector region located within its COOH terminus. This effector region, when
      separated from the holoprotein, activates Rac and acts as a potent inducer of
      actin polymerization. In addition, it binds to Sos-1 and is able to induce Rac
      specific, Sos-1-dependent guanine nucleotide exchange activity. Finally, the Eps8
      effector region mediates a direct interaction of Eps8 with F-actin, dictating
      Eps8 cellular localization. We propose a model whereby the engagement of Eps8 in
      a tricomplex with E3b1 and Sos-1 facilitates the interaction of Eps8 with Sos-1
      and the consequent activation of an Sos-1 Rac-specific catalytic ability. In this
      complex, determinants of Eps8 are responsible for the proper localization of the
      Rac-activating machine to sites of actin remodeling.

PMID- 11524439
TI  - Resistance training reduces susceptibility to eccentric exercise-induced muscle
      dysfunction in older women.
AB  - This study evaluated the effect of age on susceptibility to muscular weakness and
      damage caused by eccentric (ECC) exercise and determined whether this
      susceptibility was altered by resistance training. Young and older women
      performed concentric (CON) and ECC one repetition maximum (1 RM) strength tests
      of the quadriceps femoris. Older women also performed knee extension training for
      12 weeks. An unaccustomed bout of ECC knee extension exercise was performed
      before and after training, and CON and ECC 1 RM were reassessed for 11 days after
      the ECC bout. Magnetic resonance imaging was used to evaluate changes in muscle
      water content associated with muscle damage. Before training, older subjects
      showed a larger decline in CON (p =.008) and ECC (p =.03) strength induced by the
      unaccustomed ECC bout, compared with the young subjects. One day following the
      ECC bout, the older women showed a 24% reduction in CON and a 27% reduction in
      ECC 1 RM, compared with only 6% (CON) and 10% (ECC) in the younger women. A
      magnetic resonance imaging evaluation indicated that edema or damage was
      significantly greater in the older untrained women than it was in young women (p
      <.05), but the resistance-trained older women showed no greater muscle injury
      than the young women (p >.05). Resistance-trained older women showed no greater
      decline than sedentary young women in either CON (p >.05) or ECC (p >.05)
      strength. In conclusion, sedentary older women are more susceptible to ECC
      induced muscle dysfunction, but resistance training reduces this susceptibility.

PMID- 11524438
TI  - Age-related changes in the autophagic proteolysis of rat isolated liver cells:
      effects of antiaging dietary restrictions.
AB  - Autophagy is a process that sequesters and degrades organelles and macromolecular
      constituents of cytoplasm for cellular restructuring and repair and as a source
      of nutrients for metabolic use in early starvation. The effects of two antiaging
      dietary regimens (initiated in rats at the age of 2 months), namely, 40% dietary
      restriction (DR) and every-other-day ad-libitum feeding, that exhibited different
      effects on metabolism and similar effects on longevity on the age-related changes
      in the regulation of autophagic proteolysis were studied by monitoring the rate
      of valine release in the incubation medium from isolated liver cells of male
      albino Sprague-Dawley rats aged 2, 6, 12, 18, 24, and 27 months. (The liver cells
      were incubated in vitro with added amino acids and 10(-7) M insulin or glucagon.)
      Age-matched male albino Sprague-Dawley rats fed ad libitum served as a control.
      Results show that in ad-libitum-fed rats, after a transient increase by age 6
      months, autophagic proteolysis and regulation by amino acid exhibit a dramatic
      age-related decline, and that the age-related changes are prevented by dietary
      antiaging intervention. A comparison shows that the protective effects of DR and
      every-other-day ad-libitum feeding are partially different in 24-month-old rats
      (but the beneficial effects of the two diets on regulation of autophagic
      proteolysis are always similar). With regard to endocrine regulation, results
      confirm that the liver cell response to glucagon (but not to insulin) declines
      with increasing age, and they show that antiaging DRs significantly improve the
      effects of glucagon (and have no effect on the response to insulin). The
      interactions of age by diet, glucagon (and in older rats, insulin), and amino
      acids are significant. It is concluded that DR significantly improves the
      susceptibility of liver cells to lysosomal degradation, and it prevents decline
      with increasing age. It is suggested that improved liver autophagy and lysosomal
      degradation might be part of the antiaging mechanisms of DR.

PMID- 11524440
TI  - Food restriction enhances endogenous and corticotropin-induced plasma elevations
      of free but not total corticosterone throughout life in rats.
AB  - Chronic food restriction (FR), which retards many aging processes, enhances the
      endogenous diurnal peak of plasma total corticosterone (B) in young rats.
      Although the FR-dependent enhancement of total B disappears in aged rats,
      increased levels of the bioavailable fraction, free B, appear to be maintained.
      In young rats, we previously found that the FR-induced increase in the diurnal
      peak of total B is associated with increased adrenal response to corticotropin,
      also known as adrenocorticotropic hormone (ACTH). Here we show that the FR
      enhanced adrenal response of total B to ACTH disappears with age but that the
      enhanced response of free B is maintained. We measured the endogenous diurnal
      peak and the response to ACTH of total and free B in 10-, 16-, and 22-month-old
      ad-libitum fed and FR male Fischer 344 rats in the afternoon, when plasma B
      peaks. At 10 and 16 months, FR rats showed enhanced total plasma B responses to
      ACTH relative to ad-libitum fed rats, but not at 22 months. By contrast, the
      response of free B to ACTH was enhanced by FR at all ages. The effect of FR on
      patterns of endogenous total and free diurnal B in these three age groups
      paralleled the ACTH-response data. The enhanced adrenocortical response of FR
      rats to ACTH does not reflect an increased expression of ACTH-receptor (ACTH-R)
      mRNA, because ACTH-R mRNA/microg adrenal RNA and ACTH-R mRNA/mg adrenal weight
      did not differ between ad-libitum fed and FR rats at any age.

PMID- 11524441
TI  - Relationship between muscle strength and the time taken to complete a
      standardized walk-turn-walk test.
AB  - We examined the effects of age and gender on the relationship between knee
      strength and walking time during a walk-turn-walk test in 176 male and 168 female
      generally healthy participants of the Baltimore Longitudinal Study of Aging who
      were aged 21-89 years. Subjects were timed as they walked 50 ft (15.24 m), turned
      around, and walked back to the starting point, both at a comfortable pace and as
      fast as possible. Isokinetic concentric knee extensor strength was measured at 30
      degrees /s by using a Kin-Com dynamometer. Both comfortable and fast gait times
      increased with increasing age for both women and men, starting in middle age. An
      interaction was found between gender and age showing that older women are slower
      than older men at both paces. Gait time decreased linearly with increasing knee
      extensor strength, plateauing at higher strength levels (>130 N m for comfortable
      gait, and 190 N m for fast gait). Most women occupied the linear part of the
      curve below the plateau. Adjustment for body size, age, physical activity, and
      particularly number of steps to complete the task removed the relationship
      between strength and gait time for the comfortable gait. Women took longer to
      complete the walk-turn-walk test than men at older ages, were on the linear part
      of the strength-gait time relationship, and used more steps to complete the task,
      all of which may contribute to their greater likelihood of frailty in later
      years.

PMID- 11524442
TI  - Effect of chronic aminoguanidine treatment on age-related glycation,
      glycoxidation, and collagen cross-linking in the Fischer 344 rat.
AB  - Aminoguanidine (AG) is an inhibitor of protein modification by the advanced
      Maillard reaction. We evaluated its effects in preventing age-related collagen
      cross-linking, glycation, and glycoxidation in Fischer 344 rats by administering
      the drug in their drinking water at 1 g/l from the time they were 6 months until
      they were 24 months of age. Body weight and food and water consumption were
      consistently recorded throughout the study. Plasma glucose was measured by the
      glucose oxidase method, and collagen cross-linking was assessed by tail tendon
      break time (TBT) in urea. Glycation (furosine) and glycoxidation (pentosidine and
      carboxymethyllysine) were assessed by high-performance liquid chromatography in
      acid hydrolysates of skin and tendon collagen. Water consumption dramatically
      increased (p <.0001) after 20 months of age and was accelerated in the control
      versus AG-treated rats (p <.0001). Plasma glucose increased approximately 20% at
      age 19 months in both groups (p <.0001). TBT, glycation, and glycoxidation all
      increased significantly (p <.0001) with age. However, except for a modest
      decrease of TBT at all ages that approached significance (p =.077), AG had no
      effect on collagen glycation or glycoxidation. These results are important
      because they suggest that alpha,beta-dicarbonyl compounds that can be trapped by
      aminoguanidine do not play a major role in collagen aging in the rat. Instead,
      post-Amadori pathways involving oxidative or nonoxidative fragmentation of the
      Amadori product emerge as the more likely mechanism of collagen cross-linking in
      aging.

PMID- 11524443
TI  - Nonage versus age.

PMID- 11524444
TI  - Milestone or genomania? The relevance of the Human Genome Project to biological
      aging and the age-related diseases.

PMID- 11524445
TI  - Effects of functional ability and training on chair-rise biomechanics in older
      adults.
AB  - BACKGROUND: Difficulty in rising from a chair is common in older adults and may
      be assessed by examining the biomechanics of the rise. The purposes of this study
      were (i) to analyze the biomechanics of rise performance during chair-rise tasks
      with varying task demand in older adults with varying rise ability and (ii) to
      determine whether a strength-training program might improve chair-rise success
      and alter chair-rise biomechanics, particularly under situations of increased
      task demand. METHODS: A training group (n = 16; mean age, 82 years) completed a
      12-week strength-training regimen while a control group (n = 14; mean age, 84
      years) participated in a seated flexibility program. Outcomes included the
      ability to complete seven chair-rise tasks, and, if the chair-rise tasks were
      successful, the biomechanics of these rises. Chair-rise task demand was increased
      by lowering the seat height, restricting the use of hands, increasing rise speed,
      and limiting foot support. RESULTS: At baseline, increased chair-rise task demand
      generally required increased task completion time, increased anterior center of
      pressure (COP) placement, increased momentum, increased hip flexion, and
      increased hip and knee torque output. Those unable to rise at 100% knee height
      without the use of their hands (task NH-100), compared with those able to rise
      during task NH-100, followed this pattern in requiring increased time, more
      anterior placement of the COP, and increased hip flexion to rise in the least
      demanding tasks allowing the use of hands. However, the unable subjects generated
      less momentum and knee torque in these tasks. At 12 weeks, and compared with
      baseline and controls, the training group demonstrated changes in chair-rise
      biomechanics but no significant changes in rise success. The training subjects,
      as compared with the controls, maintained a more posterior COP, increased their
      vertical and horizontal momentum, maintained their knees in greater extension,
      and maintained their knee-torque output. CONCLUSIONS: These data demonstrate that
      subtle yet significant changes can be demonstrated in chair-rise performance as a
      result of a controlled resistance-training program. These biomechanical changes
      may represent a shift away from impairment in chair-rise ability, and, although
      the changes are small, they represent how training may reduce rise difficulty.

PMID- 11524446
TI  - Prevalence [correction of prevalance] of functional blindness, visual impairment,
      and related functional deficits among elderly Mexican Americans.
AB  - BACKGROUND: This report describes the prevalence and correlates of functional
      blindness and visual impairment among older Mexican Americans, using data on 2800
      respondents from the Hispanic Established Populations for the Epidemiological
      Study of the Elderly. METHODS: Bivariate and multivariate logistic regression
      analyses were used to examine the associations between corrected bilateral
      distant vision and sociodemographic characteristics, selected health conditions,
      self-reported health status, health care utilization, and functional dependence
      on the basis of assistance needed for basic and instrumental activities of daily
      living (ADLs). RESULTS: Using a modified Snellen test for distance visual acuity,
      5% of older Mexican Americans were found to be functionally blind, and 13.5% were
      found to be visually impaired. Vision loss was significantly associated with
      older age, lower education, hypertension, diabetes, poor self-rated health, and
      hospitalization during the year prior to the interview. Over 50% of functionally
      blind subjects required assistance with at least one basic ADL, compared with 15%
      of those who were visually impaired and 8% of those who were not visually
      impaired. CONCLUSIONS: The prevalence of functional blindness in this sample of
      elderly Mexican Americans was higher than reported for the general elderly
      population, yet they also have higher rates of adequate vision because of the low
      prevalence of visual impairment. The results suggest a need for more research on
      the prevalence and impact of functional blindness and visual impairment on the
      health of older Mexican Americans.

PMID- 11524447
TI  - Construct validation and test-retest reliability of the seniors in the community:
      risk evaluation for eating and nutrition questionnaire.
AB  - BACKGROUND: We performed two studies. Study 1 was a construct validation of
      Seniors in the Community: Risk Evaluation for Eating and Nutrition (SCREEN), a 15
      item questionnaire for assessing nutritional risk. In Study 2, we examined the
      test-retest reliability of SCREEN. METHODS: Study 1 was a cross-sectional study,
      and Study 2 was a cohort study. For Study 1, ten diverse community sites were
      used to recruit participants. A total of 128 older adults attended a clinic to
      provide medical and nutritional history and anthropometric measurements. A
      dietitian interviewed each participant. Dietitians used clinical judgment to rate
      the probability of nutritional risk from 1 (low risk) to 10 (high risk).
      Spearman's rho correlation and receiver operating characteristic curves were
      completed. An abbreviated SCREEN was developed through multiple linear regression
      analysis. In Study 2, SCREEN was randomly distributed to members of a seniors'
      recreation center where a self-selected sample (n = 124) completed two mailed
      SCREENs, 4 weeks apart. The test-retest reliability was estimated through paired
      correlations of total scores and individual items. RESULTS: In Study 1, total and
      abbreviated SCREEN scores were significantly associated with the dietitian
      nutritional risk rating (rho = -.47 and rho = -.60, respectively). Study 2
      revealed that the test-retest reliability of SCREEN was adequate. CONCLUSIONS:
      SCREEN appears to be a valid and reliable tool for identifying community-dwelling
      older adults at risk for impaired nutritional states.

PMID- 11524448
TI  - The Minnesota Senior Health Options program: an early effort at integrating care
      for the dually eligible.
AB  - BACKGROUND: Duplication of funding and resultant inefficiencies have prompted
      active consideration of pooling the funding for persons covered by both Medicare
      and Medicaid into a single managed care program. This study reports the initial
      results of the first such program. METHODS: A sample of enrollees in Minnesota
      Senior Health Options (MSHO) and two sets of controls (within the same catchment
      area and outside it) as well as their families were interviewed to assess their
      functional status and satisfaction with their medical care. Respondents included
      those living in the community and those living in nursing homes. RESULTS: The
      MSHO and control samples were generally alike in terms of demographics and
      illness patterns. The differences that were found reflected those attributable to
      geographic location more than program. The groups were also similar with regard
      to functional status. There were few satisfaction differences among the community
      dwelling samples, but the MSHO nursing residents and especially their families
      expressed more satisfaction with several aspects of care. CONCLUSIONS: Whereas no
      causal conclusions about outcomes can be drawn from a cross-sectional sample,
      there is no indication that managed care for the dually eligible population has
      profound impacts on care. However, the system of care provided to nursing home
      residents is appreciated over traditional care.

PMID- 11524449
TI  - Predictor index of mortality in dementia patients upon entry into long-term care.
AB  - BACKGROUND: The purpose of this study was to develop an algorithm that predicts
      survival in patients with dementia upon entry into long-term care. There are, as
      yet, no predictive equations developed for those in the late stages of
      Alzheimer's disease (AD). METHODS: This was a prospective, observational study of
      132 patients with dementia (61% with AD) followed for up to 5.0 years (median of
      41.0 months) after admission to a long-term care facility for dementia patients.
      Information on demographic characteristics, physical health, and cognitive,
      emotional, and behavioral characteristics was collected shortly after admission
      and entered as predictors of time until death in Cox regressions. Findings were
      used to derive an index predicting mortality. RESULTS: There were 60 deaths among
      the 132 patients (45.4% mortality), with an average survival of 22.4 months in
      those who died. Better physical health and the presence of delusions were
      associated with longer survival. These two variables were aggregated into the
      Copper Ridge Index (CRI). Each one-point increase on the CRI was associated with
      a four-fold greater likelihood of death over 5 years. CONCLUSIONS: A predictive
      equation incorporating measures of general physical health and delusions
      accurately predicted time to death in dementia patients in long-term care.

PMID- 11524450
TI  - Evaluating eye-body coordination during unrestrained functional activity in older
      persons.
AB  - BACKGROUND: Traditional paradigms for the study of ocular-motor control restrain
      subject motion and have not adequately quantified the sensorimotor strategies
      used by older persons to control gaze while performing activities of daily
      living. The purpose of our study was to describe eye-head-trunk coordination
      during a functional activity in freely moving community-dwelling older persons.
      METHODS: Thirty-five community-dwelling older persons (age range 71-92 years)
      participated in this study. Surface electro-oculography was used with an
      electromagnetic tracking device to measure vertical eye movement and linear and
      angular head position while each subject performed a stand-from-chair task.
      RESULTS: Standing from a chair involved low-frequency head motion (median z =
      0.25 Hz; median pitch = 0.32 Hz). The distribution of phase for eyes versus
      vertical body motion were skewed toward head-trunk leading, suggesting that eye
      motion follows vertical body motion. Vertical gaze, however, was in phase with
      and moved in the same direction as head pitch. CONCLUSIONS: Gaze (eye position in
      space) was an active, integrated component of the standing motion. The results
      imply that both the oculomotor system and the head motor system in older persons
      are coordinated to direct gaze and, when necessary, work to suppress the
      vestibuloocular reflex. The interaction of eye-head-trunk motion provides a basis
      for understanding how a breakdown in the gaze control mechanisms in older persons
      might contribute to the risk of falling and fall-related injuries.

PMID- 11524451
TI  - Effect of aging and diabetes on the enteroinsular axis.
AB  - BACKGROUND: The current studies were designed to examine the effect of aging and
      diabetes on the enteroinsular axis. METHODS: Healthy young control subjects (n =
      10 young; age 23 +/- 1 years; body mass index [BMI] 24 +/- 1 kg/m(2)), healthy
      elderly subjects (n = 10; age 80 +/- 2 years; BMI 26 +/- 1 kg/m(2)), and elderly
      patients with type 2 diabetes (n = 10; age 76 +/- 2 years; BMI 26 +/- 2 kg/m(2))
      underwent a 3-hour oral glucose tolerance test (glucose dose 40 gm/m(2)).
      RESULTS: Insulin responses were not different between young controls and elderly
      patients with diabetes but were significantly lower in elderly patients with
      diabetes and young controls than in elderly controls (young control: 178 +/- 27
      pM; elderly control: 355 +/- 57 pM; elderly diabetes: 177 +/- 30 pM; p <.05
      elderly control vs young control and elderly diabetes). Total glucagon-like
      peptide 1 (GLP-1) responses were not significantly different between young and
      elderly controls and patients with diabetes (young control: 15 +/- 2 pM; old
      control: 8 +/- 2 pM; elderly diabetes: 12 +/- 3 pM; p = ns). Active GLP-1
      responses were also not different between young and elderly controls and patients
      with diabetes (young control: 5 +/- 1 pM; old control: 6 +/- 1 pM; elderly
      diabetes: 7 +/- 1 pM; p = ns). However, the difference between total and active
      GLP levels was significantly greater in the young controls (young control: 10 +/-
      2 pM; old control: 2 +/- 2 pM; elderly diabetes: 4 +/- 2 pM; p <.05, young vs
      elderly). Glucose-dependent insulinotropic polypeptide responses were not
      different between young and elderly controls and between elderly controls and
      patients with diabetes but were significantly higher in elderly patients with
      diabetes than in young controls (young control: 97 +/- 12 pM; elderly control:
      121 +/- 16 pM; elderly diabetes: 173 +/- 27 pM; p <.05, young vs elderly
      diabetes). Glucagon responses were reduced in elderly controls but were similar
      in young controls and elderly patients with diabetes (young control: 15 +/- 1 pM;
      elderly control: 9 +/- 1 pM; elderly diabetes: 16 +/- 1 pM; p <.01 elderly
      control vs young control and elderly diabetes). Dipeptidyl peptidase IV levels
      were lower in both elderly controls and patients with diabetes when compared with
      young controls (young control: 0.17 +/- 0.01; elderly control: 0.15 +/- 0.01;
      elderly diabetes: 0.15 +/- 0.01 DeltaOD/20 minutes; p <.05, elderly vs young).
      CONCLUSIONS: We conclude that normal aging and diabetes are associated with
      multiple changes in the enteroinsular axis.

PMID- 11524452
TI  - Comparison of elderly nonfallers and fallers on performance measures of
      functional reach, sensory organization, and limits of stability.
AB  - BACKGROUND: Previous literature indicates that balance impairment is a primary
      risk factor in the occurrence of falls, which has led clinicians to develop gross
      standardized balance assessment tests to distinguish elderly nonfallers from
      fallers. The purpose of this study was to compare functional reach (FR), limits
      of stability (LOS), and sensory organization among elderly nonfallers and
      fallers. METHODS: FR was examined in 15 elderly nonfallers and 10 idiopathic
      fallers who were at least 60 years of age. Forceplate measures from the NeuroCom
      Smart Balance Master system, which included the LOS test and the sensory
      organization test (SOT), were used to quantify limits of stability and balance.
      Associations among the three tests were examined. RESULTS: There was no
      significant difference in mean FR distance between elderly nonfallers and fallers
      using the functional reach test. FR distance did not correlate with anterior
      displacement on the LOS test. There was a significant difference in mean
      composite score on the SOT between nonfallers and fallers as well as a
      significant positive correlation between the SOT composite score and anterior
      displacement on the LOS test for fallers. CONCLUSIONS: The results suggest that
      FR measures do not differentiate nonfallers from fallers. In contrast, this study
      demonstrates that using the SOT protocol could differentiate elderly nonfallers
      from fallers for balance impairment. Caution should be used when interpreting
      information from the FR test in determining a balance-impaired population.

PMID- 11524453
TI  - How quickly can healthy adults move their hands to intercept an approaching
      object? Age and gender effects.
AB  - BACKGROUND: The upper extremities are often used to protect the head and torso
      from impact with an object or with the ground. We tested the null hypotheses that
      neither age nor gender would affect the time required for healthy adults to move
      their upper extremities into a protective posture. METHODS: Twenty young (mean
      age 25 years) and twenty older (mean age 70 years) volunteers, with equal gender
      representation, performed a seated arm-movement task under three conditions:
      Condition 1, in which subjects were instructed to raise the hands upon cue as
      quickly as possible from thigh level to a shoulder height target; Condition 2, in
      which subjects were instructed as in Condition 1 with the addition of
      intercepting a swinging pendulum at the prescribed hand target; and Condition 3,
      in which subjects were instructed as in Condition 2 but were asked to wait as
      long as possible before initiating hand movement to intercept the pendulum. Arm
      movements were quantified using standard kinematic techniques. RESULTS: Age (p
      <.01) and gender (p <.05) affected hand movement times. In Conditions 1 and 2,
      the older women required 20% longer movement times than the other subject groups
      (335 vs 279 milliseconds; p <.01). In Condition 3, shorter movement times were
      achieved by young men (20%; p =.002) and older women (10%; p =.056) as compared
      with their respective performance in Conditions 1 and 2 because they did not
      fully decelerate their hands. The other groups slowed their movements in
      Condition 3. CONCLUSIONS: Age, gender, and perceived threat significantly
      affected movement times. However, even the slowest movement times were well
      within the time available to deploy the hands in a forward fall to the ground.

PMID- 11524454
TI  - Lateral stability during forward-induced stepping for dynamic balance recovery in
      young and older adults.
AB  - BACKGROUND: Balance dysfunction related to lateral instability has been
      associated with falls and fall-related injuries among older individuals.
      Protective stepping for dynamic balance recovery requires the effective control
      of lateral body motion. This study investigated the relationship between aging,
      falls, and lateral stability during forward-induced stepping for dynamic balance
      recovery. METHODS: Forward steps were induced by a motor-driven waist-pull system
      in 12 younger adults, 20 healthy community-dwelling older adult nonfallers, and
      18 older adults who had reported falls. Group differences in kinetic and
      kinematic stepping characteristics for a range of postural disturbance magnitudes
      were evaluated. RESULTS: Despite group similarities in anticipatory postural
      adjustments for minimizing lateral instability, the older fallers demonstrated
      significantly greater sideways body motion toward the stepping side at first-step
      foot contact and a more laterally directed foot placement. During the first step,
      forward-stepping characteristics were generally comparable between the groups,
      but the older fallers had an earlier liftoff time and longer step duration.
      CONCLUSIONS: During forward-induced protective stepping, otherwise healthy older
      adults who had experienced falls showed particular differences in their control
      of lateral body motion that were not attributable to changes in anticipatory
      postural mechanisms. Aging changes in controlling lateral body motion during
      protective stepping appear to involve factors that intervene between the first
      step liftoff and foot contact and/or adaptations in stepping patterns related to
      prior planning.

PMID- 11524455
TI  - Regulation of hyperpolarization-activated HCN channel gating and cAMP modulation
      due to interactions of COOH terminus and core transmembrane regions.
AB  - Members of the hyperpolarization-activated cation (HCN) channel family generate
      HCN currents (I(h)) that are directly regulated by cAMP and contribute to
      pacemaking activity in heart and brain. The four different HCN isoforms show
      distinct biophysical properties. In cell-free patches from Xenopus oocytes, the
      steady-state activation curve of HCN2 channels is 20 mV more hyperpolarized
      compared with HCN1. Whereas the binding of cAMP to a COOH-terminal cyclic
      nucleotide binding domain (CNBD) markedly shifts the activation curve of HCN2 by
      17 mV to more positive potentials, the response of HCN1 is much less pronounced
      (4 mV shift). A previous deletion mutant study suggested that the CNBD inhibits
      hyperpolarization-gating in the absence of cAMP; the binding of cAMP shifts
      gating to more positive voltages by relieving this inhibition. The differences in
      basal gating and cAMP responsiveness between HCN1 and HCN2 were proposed to
      result from a greater inhibitory effect of the CNBD in HCN2 compared with HCN1.
      Here, we use a series of chimeras between HCN1 and HCN2, in which we exchange the
      NH(2) terminus, the transmembrane domain, or distinct domains of the COOH
      terminus, to investigate further the molecular bases for the modulatory action of
      cAMP and for the differences in the functional properties of the two channels.
      Differences in cAMP regulation between HCN1 and HCN2 are localized to sequence
      differences within the COOH terminus of the two channels. Surprisingly, exchange
      of the CNBDs between HCN1 and HCN2 has little effect on basal gating and has only
      a modest one on cAMP modulation. Rather, differences in cAMP modulation depend on
      the interaction between the CNBD and the C-linker, a conserved 80-amino acid
      region that connects the last (S6) transmembrane segment to the CNBD. Differences
      in basal gating depend on both the core transmembrane domain and the COOH
      terminus. These data, taken in the context of the previous data on deletion
      mutants, suggest that the inhibitory effect of the CNBD on basal gating depends
      on its interactions with both the C-linker and core transmembrane domain of the
      channel. The extent to which cAMP binding is able to relieve this inhibition is
      dependent on the interaction between the C-linker and the CNBD.

PMID- 11524457
TI  - Arterial branching within the confines of fractal L-system formalism.
AB  - Parametric Lindenmayer systems (L-systems) are formulated to generate branching
      tree structures that can incorporate the physiological laws of arterial
      branching. By construction, the generated trees are de facto fractal structures,
      and with appropriate choice of parameters, they can be made to exhibit some of
      the branching patterns of arterial trees, particularly those with a preponderant
      value of the asymmetry ratio. The question of whether arterial trees in general
      have these fractal characteristics is examined by comparison of pattern with
      vasculature from the cardiovascular system. The results suggest that parametric L
      systems can be used to produce fractal tree structures but not with the
      variability in branching parameters observed in arterial trees. These parameters
      include the asymmetry ratio, the area ratio, branch diameters, and branching
      angles. The key issue is that the source of variability in these parameters is
      not known and, hence, it cannot be accurately reproduced in a model. L-systems
      with a random choice of parameters can be made to mimic some of the observed
      variability, but the legitimacy of that choice is not clear.

PMID- 11524456
TI  - Volume-dependent ATP-conductive large-conductance anion channel as a pathway for
      swelling-induced ATP release.
AB  - In mouse mammary C127i cells, during whole-cell clamp, osmotic cell swelling
      activated an anion channel current, when the phloretin-sensitive, volume
      activated outwardly rectifying Cl(-) channel was eliminated. This current
      exhibited time-dependent inactivation at positive and negative voltages greater
      than around +/-25 mV. The whole-cell current was selective for anions and
      sensitive to Gd(3)+. In on-cell patches, single-channel events appeared with a
      lag period of approximately 15 min after a hypotonic challenge. Under isotonic
      conditions, cell-attached patches were silent, but patch excision led to
      activation of currents that consisted of multiple large-conductance unitary
      steps. The current displayed voltage- and time-dependent inactivation similar to
      that of whole-cell current. Voltage-dependent activation profile was bell-shaped
      with the maximum open probability at -20 to 0 mV. The channel in inside-out
      patches had the unitary conductance of approximately 400 pS, a linear current
      voltage relationship, and anion selectivity. The outward (but not inward) single
      channel conductance was suppressed by extracellular ATP with an IC(50) of 12.3 mM
      and an electric distance (delta) of 0.47, whereas the inward (but not outward)
      conductance was inhibited by intracellular ATP with an IC(50) of 12.9 mM and
      delta of 0.40. Despite the open channel block by ATP, the channel was ATP
      conductive with P(ATP)/P(Cl) of 0.09. The single-channel activity was sensitive
      to Gd(3)+, SITS, and NPPB, but insensitive to phloretin, niflumic acid, and
      glibenclamide. The same pharmacological pattern was found in swelling-induced ATP
      release. Thus, it is concluded that the volume- and voltage-dependent ATP
      conductive large-conductance anion channel serves as a conductive pathway for the
      swelling-induced ATP release in C127i cells.

PMID- 11524458
TI  - Functional effects of central core disease mutations in the cytoplasmic region of
      the skeletal muscle ryanodine receptor.
AB  - Central core disease (CCD) is a human myopathy that involves a dysregulation in
      muscle Ca(2)+ homeostasis caused by mutations in the gene encoding the skeletal
      muscle ryanodine receptor (RyR1), the protein that comprises the calcium release
      channel of the SR. Although genetic studies have clearly demonstrated linkage
      between mutations in RyR1 and CCD, the impact of these mutations on release
      channel function and excitation-contraction coupling in skeletal muscle is
      unknown. Toward this goal, we have engineered the different CCD mutations found
      in the NH(2)-terminal region of RyR1 into a rabbit RyR1 cDNA (R164C, I404M,
      Y523S, R2163H, and R2435H) and characterized the functional effects of these
      mutations after expression in myotubes derived from RyR1-knockout (dyspedic)
      mice. Resting Ca(2)+ levels were elevated in dyspedic myotubes expressing four of
      these mutants (Y523S > R2163H > R2435H R164C > I404M RyR1). A similar rank order
      was also found for the degree of SR Ca(2)+ depletion assessed using maximal
      concentrations of caffeine (10 mM) or cyclopiazonic acid (CPA, 30 microM).
      Although all of the CCD mutants fully restored L-current density, voltage-gated
      SR Ca(2)+ release was smaller and activated at more negative potentials for
      myotubes expressing the NH(2)-terminal CCD mutations. The shift in the voltage
      dependence of SR Ca(2)+ release correlated strongly with changes in resting
      Ca(2)+, SR Ca(2)+ store depletion, and peak voltage-gated release, indicating
      that increased release channel activity at negative membrane potentials promotes
      SR Ca(2)+ leak. Coexpression of wild-type and Y523S RyR1 proteins in dyspedic
      myotubes resulted in release channels that exhibited an intermediate degree of SR
      Ca(2)+ leak. These results demonstrate that the NH(2)-terminal CCD mutants
      enhance release channel sensitivity to activation by voltage in a manner that
      leads to increased SR Ca(2)+ leak, store depletion, and a reduction in voltage
      gated Ca(2)+ release. Two fundamentally distinct cellular mechanisms (leaky
      channels and EC uncoupling) are proposed to explain how altered release channel
      function caused by different mutations in RyR1 could result in muscle weakness in
      CCD.

PMID- 11524459
TI  - Neutralization of gating charges in domain II of the sodium channel alpha subunit
      enhances voltage-sensor trapping by a beta-scorpion toxin.
AB  - beta-Scorpion toxins shift the voltage dependence of activation of sodium
      channels to more negative membrane potentials, but only after a strong
      depolarizing prepulse to fully activate the channels. Their receptor site
      includes the S3-S4 loop at the extracellular end of the S4 voltage sensor in
      domain II of the alpha subunit. Here, we probe the role of gating charges in the
      IIS4 segment in beta-scorpion toxin action by mutagenesis and functional analysis
      of the resulting mutant sodium channels. Neutralization of the positively charged
      amino acid residues in the IIS4 segment by mutation to glutamine shifts the
      voltage dependence of channel activation to more positive membrane potentials and
      reduces the steepness of voltage-dependent gating, which is consistent with the
      presumed role of these residues as gating charges. Surprisingly, neutralization
      of the gating charges at the outer end of the IIS4 segment by the mutations
      R850Q, R850C, R853Q, and R853C markedly enhances beta-scorpion toxin action,
      whereas mutations R856Q, K859Q, and K862Q have no effect. In contrast to wild
      type, the beta-scorpion toxin Css IV causes a negative shift of the voltage
      dependence of activation of mutants R853Q and R853C without a depolarizing
      prepulse at holding potentials from -80 to -140 mV. Reaction of mutant R853C with
      2-aminoethyl methanethiosulfonate causes a positive shift of the voltage
      dependence of activation and restores the requirement for a depolarizing prepulse
      for Css IV action. Enhancement of sodium channel activation by Css IV causes
      large tail currents upon repolarization, indicating slowed deactivation of the
      IIS4 voltage sensor by the bound toxin. Our results are consistent with a voltage
      sensor-trapping model in which the beta-scorpion toxin traps the IIS4 voltage
      sensor in its activated position as it moves outward in response to
      depolarization and holds it there, slowing its inward movement on deactivation
      and enhancing subsequent channel activation. Evidently, neutralization of R850
      and R853 removes kinetic barriers to binding of the IIS4 segment by Css IV, and
      thereby enhances toxin-induced channel activation.

PMID- 11524460
TI  - KcsA: it's a potassium channel.
AB  - Ion conduction and selectivity properties of KcsA, a bacterial ion channel of
      known structure, were studied in a planar lipid bilayer system at the single
      channel level. Selectivity sequences for permeant ions were determined by
      symmetrical solution conductance (K(+) > Rb(+), NH(4)(+), Tl(+) >> Cs(+), Na(+),
      Li(+)) and by reversal potentials under bi-ionic or mixed-ion conditions (Tl(+) >
      K(+) > Rb(+) > NH(4)(+) >> Na(+), Li(+)). Determination of reversal potentials
      with submillivolt accuracy shows that K(+) is over 150-fold more permeant than
      Na(+). Variation of conductance with concentration under symmetrical salt
      conditions is complex, with at least two ion-binding processes revealing
      themselves: a high affinity process below 20 mM and a low affinity process over
      the range 100-1,000 mM. These properties are analogous to those seen in many
      eukaryotic K(+) channels, and they establish KcsA as a faithful structural model
      for ion permeation in eukaryotic K(+) channels.

PMID- 11524461
TI  - Altered state dependence of c-type inactivation in the long and short forms of
      human Kv1.5.
AB  - Evidence from both human and murine cardiomyocytes suggests that truncated
      isoforms of Kv1.5 can be expressed in vivo. Using whole-cell patch-clamp
      recordings, we have characterized the activation and inactivation properties of
      Kv1.5DeltaN209, a naturally occurring short form of human Kv1.5 that lacks
      roughly 75% of the T1 domain. When expressed in HEK 293 cells, this truncated
      channel exhibited a V(1/2) of -19.5 +/- 0.9 mV for activation and -35.7 +/- 0.7
      mV for inactivation, compared with a V(1/2) of -11.2 +/- 0.3 mV for activation
      and -0.9 +/- 1.6 mV for inactivation in full-length Kv.15. Kv1.5DeltaN209
      channels exhibited several features rarely observed in voltage-gated K(+)
      channels and absent in full-length Kv1.5, including a U-shaped voltage dependence
      of inactivation and "excessive cumulative inactivation," in which a train of
      repetitive depolarizations resulted in greater inactivation than a continuous
      pulse. Kv1.5DeltaN209 also exhibited a stronger voltage dependence to recovery
      from inactivation, with the time to half-recovery changing e-fold over 30 mV
      compared with 66 mV in full-length Kv1.5. During trains of human action potential
      voltage clamps, Kv1.5DeltaN209 showed 30-35% greater accumulated inactivation
      than full-length Kv1.5. These results can be explained with a model based on an
      allosteric model of inactivation in Kv2.1 (Klemic, K.G., C.-C. Shieh, G.E.
      Kirsch, and S.W. Jones. 1998. Biophys. J. 74:1779-1789) in which an absence of
      the NH(2) terminus results in accelerated inactivation from closed states
      relative to full-length Kv1.5. We suggest that differential expression of
      isoforms of Kv1.5 may contribute to K(+) current diversity in human heart and
      many other tissues.

PMID- 11524462
TI  - Buy some today: can generics be safely substituted for brand-name drugs?

PMID- 11524463
TI  - Is a muscle biopsy in Duchenne dystrophy really necessary?

PMID- 11524465
TI  - Malignant rolandic-sylvian epilepsy in children: diagnosis, treatment, and
      outcomes.
AB  - OBJECTIVE: To describe the diagnosis, treatment, and outcomes in children with
      malignant rolandic-sylvian epilepsy (MRSE), defined as a form of epilepsy
      characterized by sensorimotor seizures, medical refractoriness, normal MRI,
      frontocentrotemporal EEG spikes, rolandic-sylvian spike sources on
      magnetoencephalography (MEG), and cognitive problems. METHODS: A retrospective
      chart analysis of seven patients who had shown these characteristics and
      undergone extensive diagnostic testing, including MEG and intracranial video-EEG
      was performed. RESULTS: Interictal scalp EEG spikes were seen over the
      frontocentrotemporal regions bilaterally (6) and unilaterally (1). MEG showed
      spike sources in the perisylvian region in two patients (both bilateral) and in
      the perirolandic fissure in five (two bilateral). Three patients required
      bilateral subdural strips to lateralize seizures before electrocorticography.
      Final electrocorticograms showed an ictal onset zone around the rolandic (four
      cases) and rolandic-sylvian regions (three cases). Six patients showed
      neuropsychological deficits. After cortical excision and multiple subpial
      transection, three were seizure free and four had seizures rarely (30 months'
      mean follow-up). No child had a permanent deficit in sensorimotor or cognitive
      functions, although two showed exacerbation of preexisting attentional deficits.
      Tissue analysis showed definite evidence of neuronal migration disorders (3) and
      gliosis (2). CONCLUSIONS: MEG was helpful for localizing both malignant rolandic
      sylvian neuronal activities and functional cortex. Successive neuropsychological
      assessments are necessary to detect cognitive deterioration and indicate remedial
      programming. If, after careful observation over at least 5 years, surgery is
      considered to control refractory seizures, intracranial video-EEG is needed to
      localize the epileptogenic zone.

PMID- 11524464
TI  - Effect of food on absorption of Dilantin Kapseals and Mylan extended phenytoin
      sodium capsules.
AB  - BACKGROUND: Because of phenytoin's narrow therapeutic index and nonlinear
      pharmacokinetics, food-induced alterations in absorption may markedly influence
      drug concentrations and, in turn, safety and effectiveness. Potential food
      associated differences between 100-mg Mylan (Mylan Pharmaceuticals) extended
      release phenytoin sodium capsules and Parke-Davis 100-mg Dilantin Kapseals were
      examined. METHODS: A single-dose, two-way crossover study was conducted in 24
      healthy subjects to determine the effect of a high-fat meal on the
      pharmacokinetics of both formulations. Pharmacokinetic parameters were estimated
      by noncompartmental methods. The impact of switching products on steady-state
      phenytoin concentrations was investigated through simulation using
      pharmacokinetic data previously obtained from 30 epileptic patients. RESULTS:
      Based on AUC(0-infinity), bioavailability of the Mylan product administered with
      food was 13% lower than that observed with Dilantin Kapseals. Simulations of
      substituting the Mylan product for Dilantin suggested that the 13% decrease in
      bioavailability would result in a median 37% decrease (range 19 to 58%) in plasma
      phenytoin concentrations when the drug is given with food; in 46% of patients,
      phenytoin concentrations would likely fall below the therapeutic range of 10 to
      20 mg/L. Simulations of substituting Dilantin for the Mylan product suggested
      that the 15% increase in bioavailability would result in a median 102% increase
      (range 24 to >150%) in plasma phenytoin concentrations, with 84% of patients
      having phenytoin concentrations above the therapeutic range. CONCLUSIONS: Results
      suggest that when taking phenytoin sodium with food, product switches may result
      in either side effects or loss of seizure control.

PMID- 11524466
TI  - Bilateral hippocampal atrophy: consequences to verbal memory following temporal
      lobectomy.
AB  - BACKGROUND: Bilateral hippocampal damage is a risk factor for memory decline
      after anterior temporal lobectomy (ATL). OBJECTIVE: To investigate verbal memory
      outcome in patients with temporal lobe epilepsy (TLE) with either unilateral or
      bilateral hippocampal atrophy as measured by MRI. METHODS: The authors selected
      60 patients with TLE who had undergone ATL (left = 31, right = 29). They
      determined normalized MRI hippocampal volumes by cursor tracing 1.5-mm slices
      from three-dimensional MRI acquisition. Hippocampal volumes were defined as
      atrophic if the volumes were below 2 SD for control subjects. Bilateral
      hippocampal atrophy was present in 10 patients with left TLE and 11 patients with
      right TLE. The authors assessed acquisition, retrieval, and recognition
      components of verbal memory both before and after ATL. RESULTS: Groups did not
      differ across age, education, intelligence, age at seizure onset, or seizure
      duration. Seizure-free rates after ATL were 70% or higher for all groups. Before
      surgery, patients with left TLE displayed worse verbal acquisition performance
      compared with patients with right TLE. Patients with left TLE with bilateral
      hippocampal volume loss displayed the lowest performance across all three memory
      components. After surgery, both groups of patients with left TLE exhibited worse
      verbal memory outcome compared with patients with right TLE. Bilateral
      hippocampal atrophy did not worsen outcome in the patients with right TLE. A
      higher proportion of patients with left TLE with bilateral hippocampal atrophy
      experienced memory decline compared with the other TLE groups. CONCLUSION:
      Bilateral hippocampal atrophy in the presence of left TLE is associated with
      worse verbal memory before and after ATL compared with patients with unilateral
      hippocampal volume loss or right TLE with bilateral hippocampal volume loss.

PMID- 11524467
TI  - High-dose estradiol improves cognition for women with AD: results of a randomized
      study.
AB  - OBJECTIVE: To characterize the cognitive and neuroendocrine response to treatment
      with a high dose of estrogen for postmenopausal women with AD. METHODS: Twenty
      postmenopausal women with AD were randomized to receive either 0.10 mg/day of 17
      beta-estradiol by skin patch or a placebo patch for 8 weeks. Subjects were
      evaluated at baseline, at weeks 3, 5, and 8 during treatment, and again 8 weeks
      after treatment termination. During each visit, cognition was assessed with a
      battery of neuropsychological tests, and blood samples were collected to measure
      plasma estradiol as well as several other neuroendocrine markers of interest.
      RESULTS: Significant effects of estrogen treatment were observed on attention
      (Stroop Color Word Interference Test), verbal memory (Buschke Selective Reminding
      Test), and visual memory (Figure Copy/Memory). In addition, women treated with
      estrogen demonstrated improved performance on a test of semantic memory (Boston
      Naming Test) compared with subjects who received a placebo. Estrogen appeared to
      have a suppressive effect on the insulin-like growth factor (IGF) system such
      that plasma concentration of IGF binding protein-3 was significantly reduced and
      plasma levels of estradiol and IGF-I were negatively correlated during estrogen
      treatment. CONCLUSIONS: Administration of a higher dose of estrogen may enhance
      attention and memory for postmenopausal women with AD. Although these findings
      provide further clinical evidence to support a cognitive benefit of estrogen for
      women with AD, studies evaluating the effect of estradiol administration, in
      particular, using larger sample sizes and for longer treatment durations are
      warranted before the therapeutic potential of estrogen replacement for women with
      AD can be firmly established.

PMID- 11524468
TI  - A 24-week, randomized, double-blind study of donepezil in moderate to severe
      Alzheimer's disease.
AB  - OBJECTIVE: To investigate the efficacy and safety of donepezil in patients with
      moderate to severe AD (standardized Mini-Mental State Examination [sMMSE] scores
      of 5 to 17; Functional Assessment Staging score < or =6 at baseline). METHODS:
      Two-hundred ninety patients were randomized to treatment in this 24-week, double
      blind, placebo-controlled trial. Patients received either donepezil 5 mg/day for
      the first 28 days and 10 mg/day thereafter as per the clinician's judgment (n =
      144) or placebo (n = 146). The primary outcome measure was the Clinician's
      Interview-Based Impression of Change with caregiver input (CIBIC+). RESULTS:
      Patients' mean age was 73.6 years (range 48 to 92 years). Baseline demographics
      were similar between the treatment groups. Least squares (LS) mean +/- SE sMMSE
      scores at baseline were 11.7 +/- 0.35 for the donepezil group and 12.0 +/- 0.34
      for the placebo group. Patients receiving donepezil showed benefits on the
      CIBIC+, compared with placebo, at all visits up to week 24 (p < 0.001) and at
      week 24 last observation carried forward (LOCF) (p < 0.0001). All other secondary
      measures (including sMMSE, Severe Impairment Battery, Disability Assessment for
      Dementia, Functional Rating Scale, and Neuropsychiatric Inventory) showed
      significant differences between the groups in favor of donepezil at week 24 LOCF.
      Eighty-four percent of donepezil- and 86% of placebo-treated patients completed
      the trial. Adverse events (AE) were experienced by 83% of donepezil- and 80% of
      placebo-treated patients, the majority of which were rated mild in severity; 8%
      of donepezil- and 6% of placebo-treated patients discontinued because of AE.
      Laboratory and vital sign abnormalities were similar between the treatment
      groups. CONCLUSION: These data suggest that donepezil's benefits extend into more
      advanced stages of AD than those previously investigated, with very good
      tolerability.

PMID- 11524469
TI  - Screening for PS1 mutations in a referral-based series of AD cases: 21 novel
      mutations.
AB  - BACKGROUND: Mutations in the presenilin-1 gene (PS1) account for a majority of
      patients with early-onset familial AD. However, the clinical indications and
      algorithms for genetic testing in dementia are still evolving. METHODS: The
      entire open reading frame of the PS1 gene was sequenced in a series of 414
      consecutive patients referred for diagnostic testing, including 372 patients with
      AD and 42 asymptomatic persons with a strong family history of AD. RESULTS: Forty
      eight independent patients screened had a PS1 mutation including 21 novel
      mutations. In addition, 3% of subjects (11/413) had a known polymorphism, the
      Glu318Gly substitution. The majority of the mutations were missense substitutions
      but there were three insertions and Delta exon 10 mutation. With six exceptions
      (codons 35, 178, 352, 354, 358, and 365) most of the mutations occurred at
      residues conserved in the homologous PS2 gene or in PS1 of other species.
      CONCLUSIONS: Eleven percent of a referral-based series of patients with AD can be
      explained by coding sequence mutations in the PS1 gene. The high frequency of PS1
      mutations in this study indicates that screening for PS1 mutations in AD is
      likely to be successful, especially when directed at patients with a positive
      family history with onset before 60 years (90% of those with PS1 mutations were
      affected by age 60 years). This will also have significance for the secondary
      identification of at-risk relatives who might be candidates for future
      prophylactic therapies for AD.

PMID- 11524470
TI  - Brain metabolite concentration and dementia severity in Alzheimer's disease: a
      (1)H MRS study.
AB  - OBJECTIVE: (1)H-MRS studies have shown abnormalities in brain levels of myo
      inositol (mI) and N-acetyl aspartate (NAA) in AD, but the relation of these
      abnormalities with dementia severity was not examined. The authors sought to
      determine whether altered brain levels of mI and other metabolites occur in mild
      AD and whether they change as dementia severity worsens. METHODS: The authors
      used (1)H-MRS with external standards to measure absolute brain concentrations of
      mI, NAA, total creatine (Cr), and choline (Cho)-containing compounds in 21
      subjects with AD and 17 age- and sex-matched controls in occipital and left and
      right parietal regions. RESULTS: Concentrations of NAA were significantly
      decreased, whereas mI and Cr concentrations were significantly increased in all
      three brain regions in subjects with AD compared with controls. Higher
      concentrations of mI and Cr occurred even in mild AD. A discriminant analysis of
      the (1)H-MRS data combined with CSF volume measurements distinguished subjects
      with AD, ranging from mild to severe dementia, from controls with 100% correct
      classification. NAA concentration, though not other metabolites, was positively
      correlated with Mini-Mental State Examination score. CONCLUSION: The measurements
      with (1)H-MRS of absolute metabolite concentrations in the neocortex showed
      abnormal concentrations of brain metabolites in AD; these metabolite
      concentrations do not necessarily correlate with disease severity. Although
      changes in myo-inositol and creatine occur in the early stages of AD,
      abnormalities of N-acetyl aspartate do not occur in mild AD but progressively
      change with dementia severity. Further, subjects with mild AD can be
      differentiated from controls with (1)H-MRS.

PMID- 11524471
TI  - Evidence for cortical "disconnection" as a mechanism of age-related cognitive
      decline.
AB  - BACKGROUND: Normal aging is accompanied by a decline of cognitive abilities, and
      executive skills may be affected selectively, but the underlying mechanisms
      remain obscure and preventive strategies are lacking. It has been suggested that
      cortical "disconnection" due to the loss of white matter fibers may play an
      important role. But, to date, there has been no direct demonstration of
      structural disconnection in humans in vivo. METHODS: The authors used diffusion
      tensor MRI to look for evidence of ultrastructural changes in cerebral white
      matter in a group of 20 elderly volunteers with normal conventional MRI scans,
      and a group of 10 younger controls. The older group also underwent
      neuropsychological assessment. RESULTS: Diffusional anisotropy, a marker of white
      matter tract integrity, was reduced in the white matter of older subjects and
      fell linearly with increasing age in the older group. Mean diffusivity was higher
      in the older group and increased with age. These changes were maximal in anterior
      white matter. In the older group, anterior mean diffusivity correlated with
      executive function assessed by the Trail Making Test. CONCLUSIONS: These findings
      provide direct evidence that white matter tract disruption occurs in normal aging
      and would be consistent with the cortical disconnection hypothesis of age-related
      cognitive decline. Maximal changes in anterior white matter provide a plausible
      structural basis for selective loss of executive functions. In addition to
      providing new information about the biological basis of cognitive abilities,
      diffusion tensor MRI may be a sensitive tool for assessing interventions aimed at
      preventing cognitive decline.

PMID- 11524472
TI  - Evidence-based measurement: which disability scale for neurologic rehabilitation?
AB  - OBJECTIVE: To compare the 10-item Barthel Index (BI), 18-item Functional
      Independence Measure (FIM), and 30-item Functional Independence Measure +
      Functional Assessment Measure (FIM+FAM) as measures of disability outcomes for
      neurologic rehabilitation. METHODS: A total of 149 inpatients from two
      rehabilitation units in South England specializing in neurologic disorders were
      studied. Traditional psychometric methods were used to evaluate and compare
      acceptability (score distributions), reliability (internal consistency,
      intrarater reproducibility), validity (concurrent, convergent and discriminant
      construct), and responsiveness (standardized response mean). RESULTS: All three
      rating scales satisfied recommended criteria for reliable and valid measurement
      of disability, and are acceptable and responsive in this study sample. The FIM
      and FIM+FAM total scales are psychometrically similar measures of global
      disability. The BI, FIM, and FIM+FAM motor scales are psychometrically similar
      measures of physical disability. The FIM and FIM+FAM cognitive scales are
      psychometrically similar measures of physical disability. CONCLUSIONS: In the
      sample studied, the BI, FIM, FIM+FAM have similar measurement properties, when
      examined using traditional psychometric analyses. Although instruments with more
      items and item response categories generate more qualitative information about an
      outcome, they may not improve its measurement. Results highlight the importance
      of using recognized techniques of scale construction to develop health outcome
      measures.

PMID- 11524473
TI  - Diagnosis of Duchenne dystrophy by enhanced detection of small mutations.
AB  - OBJECTIVE: To determine whether detection of small mutations of the dystrophin
      gene can be increased using an enhanced method of single-strand conformation
      polymorphism analysis. BACKGROUND: Usual methods of DNA analysis for Duchenne
      dystrophy cannot identify mutations in one-third of cases. Muscle biopsy, with
      its inherent risks and added liability for patients with Duchenne dystrophy,
      becomes the sole method of diagnosis. Even with a tissue diagnosis of dystrophin
      deficiency, many families are excluded from carrier detection and prenatal
      diagnosis. METHODS: Genomic DNA from a cohort of 93 patients with Duchenne
      dystrophy without identifiable gene mutations was screened for mutations. In each
      case, 22 kilobases of genomic DNA were scanned, including all 79 exons of the
      dystrophin gene, adjacent intronic regions, and six alternative exons 1. RESULTS:
      Sixty-eight (73%) had small mutations, including 34 nonsense mutations, 27
      microdeletions and insertions, and 7 splice site mutations. No missense mutations
      were found. One nonsense mutation in exon 59 was detected in four patients. Most
      mutations were new; 54 of 62 different small mutations have not been reported.
      Mutations were found throughout the gene: 24% in the first quartile, 31% in the
      second, 16% in the third, and 29% in the fourth. CONCLUSIONS: A highly sensitive
      single-strand conformation polymorphism method substantially increased detection
      of small dystrophin gene mutations and made it possible to diagnose approximately
      90% of patients with Duchenne dystrophy by DNA analysis. These findings, combined
      with cost savings and safety issues, provide compelling reasons to consider DNA
      analysis as the initial diagnostic test for the suspected dystrophin-deficient
      patient.

PMID- 11524474
TI  - Cognitive impairment in sporadic ALS: a pathologic continuum underlying a
      multisystem disorder.
AB  - BACKGROUND: Traditionally considered a motor neuron-selective disorder, the
      clinical manifestations of ALS can include a frontotemporal dementia. Although
      the pathologic substrate of cognitive impairment remains to be defined, the
      presence of ubiquitin-immunoreactive (Ub+) intraneuronal inclusions in cortical
      regions has been suggested to constitute a pathologic marker of this process.
      METHODS: The authors compared the neuropathological features of four cognitively
      impaired patients with ALS, four cognitively intact patients with ALS, and four
      neurologically normal patients. The extent and load of Ub+ neuronal inclusions,
      Ub+ dystrophic neurites, and superficial linear spongiosis (SLS) was determined
      among a number of cortical, hippocampal, and subcortical regions. RESULTS:
      Although Ub+, alpha-synuclein-negative, and tau-negative neuronal inclusions were
      observed in both cognitively impaired and cognitively intact patients with ALS,
      their density and extent was greater among the former, with the difference
      greatest in the cingulate gyrus. Ub+ neurites were observed in a similar
      distribution. Only the presence of SLS, affecting the first and second cortical
      layers, reliably distinguished between the cognitively impaired and cognitively
      intact ALS subpopulations. In three of four cognitively impaired patients with
      ALS, SLS was associated with transcortical microglial activation, in the absence
      of detectable differences in astrocytosis, density of calbindin or parvalbumin
      neurons, or optical density of synaptophysin and SNAP-25. CONCLUSIONS: Although
      intraneuronal Ub+ inclusions and dystrophic neurites are observed in both ALS
      subpopulations, the presence of cognitive impairment was associated with a
      greater distribution and load of both neuropathologic features, suggesting a
      disease continuum. Moreover, cognitive impairment was uniformly associated with
      superficial linear spongiosis, a pathologic feature common to several forms of
      frontotemporal dementia.

PMID- 11524475
TI  - Clinical markers of early disease in persons near onset of Huntington's disease.
AB  - OBJECTIVE: There is increasing evidence that neuron loss precedes the phenotypic
      expression of Huntington's disease (HD). As genes for late-onset
      neurodegenerative diseases are identified, the need for accurate assessment of
      phenoconversion (i.e., the transition from health to the disease phenotype) will
      be important. METHODS: Prospective longitudinal evaluation using the Unified
      Huntington's Disease Rating Scale (UHDRS) was conducted by Huntington Study Group
      members from 36 sites. There were 260 persons considered "at risk" for HD who
      initially did not have manifest disease and had at least one subsequent
      evaluation. Repeat UHDRS data, obtained an average of 2 years later, showed that
      70 persons were given a diagnosis of definite HD based on the quantified
      neurologic examination. RESULTS: Baseline cognitive performances were
      consistently worse for the at-risk group who demonstrated conversion to a
      definitive diagnosis compared with those who did not. Longitudinal change scores
      showed that the at-risk group who did not demonstrate manifest disease during the
      follow-up study period demonstrated improvements in all cognitive tests, whereas
      performances in the at-risk group demonstrating conversion to disease during the
      study declined across cognitive domains. CONCLUSIONS: Neuropsychological measures
      show impairment 2 years before the development of more manifest motor disease.
      Findings suggest that these brief cognitive measures administered over time may
      capture early striatal neural loss in HD.

PMID- 11524476
TI  - Deep brain stimulation in the treatment of Parkinson's disease: a cost
      effectiveness analysis.
AB  - BACKGROUND: In treating PD, deep brain stimulation (DBS) has shown great promise
      in a series of uncontrolled studies. OBJECTIVE: To estimate the incremental cost
      effectiveness of DBS compared with the best medical management in late-stage PD.
      METHODS: The authors constructed a decision model to determine the lifetime
      incremental cost effectiveness between two options in patients with PD aged 50
      years and older: 1) best medical management and 2) DBS. As the long-term efficacy
      of DBS (>3 years) is not known, key assumptions regarding the procedure's long
      term durability were made. Costs were in US 2000 dollars, and quality-adjusted
      life year (QALY) was the effectiveness measure. Base assumptions were that
      quality of life (QOL) in patients with late-stage PD is 0.55 (0-to-1 scale, 1 is
      perfect health) and that DBS benefits are constant for 4 years, eroding gradually
      over the next 5 years until at parity with those produced by best medical
      management. Incremental cost-effectiveness and sensitivity analyses were
      performed. RESULTS: Under base-case assumptions, DBS provides an additional 0.72
      QALY at an additional cost of $35,000 compared with best medical management that
      results in an incremental cost-effectiveness ratio (C/E) of $49,000. QOL
      increases of between 18 and 30% resulted in questionable cost effectiveness. QOL
      increases of between 6 and 18% resulted in incremental C/E ratios not usually
      considered cost effective (>100,000/QALY). CONCLUSIONS: The results suggest that
      DBS may be cost effective in treating PD if QOL improves 18% or more compared
      with those receiving best medical management. This underscores the need for
      randomized, controlled, prospective DBS experiments including QOL and economic
      components.

PMID- 11524477
TI  - Increased glutamate in CSF and plasma of patients with HIV dementia.
AB  - BACKGROUND: Experimental evidence suggests that excitotoxicity might play a major
      role in HIV-induced neurodegeneration. However, few studies have investigated the
      role of endogenous glutamate in patients with HIV dementia. OBJECTIVE: To analyze
      CSF and plasma glutamate levels in 30 patients with AIDS with different dementia
      severity compared with 10 patients with other neurologic disorders, 11 healthy
      control subjects, and 10 patients with Alzheimer-type dementia. METHODS: CSF and
      plasma glutamate levels were measured by reverse-phase high-performance liquid
      chromatography followed by fluorometric analysis. RESULTS: Glutamate CSF levels
      were increased fivefold in the patients with HIV vs normal control subjects (p =
      0.001), patients with Alzheimer-type dementia (p < 0.0001), and patients with
      other neurologic disorders (p < 0.01). CSF glutamate levels were also related to
      the degree of dementia (p < 0.02) and brain atrophy (p < 0.002). Plasma levels
      were also higher in the patients with HIV (p < 0.0001) but did not correlate with
      either clinical or imaging features. CONCLUSION: Increased CSF glutamate may
      originate within the CNS and may play a pathogenetic role in HIV dementia, thus
      supporting the treatment of these patients with glutamate receptor antagonists.

PMID- 11524478
TI  - Fatigue is not associated with raised inflammatory markers in multiple sclerosis.
AB  - BACKGROUND: The pathogenesis of fatigue in patients with MS is poorly understood.
      OBJECTIVE: To test the hypothesis that fatigue in MS is related to inflammatory
      disease activity as measured by systemic markers of inflammation. METHODS:
      Fatigue as assessed by the Fatigue Questionnaire Scale (FQS) and Krupp's Fatigue
      Severity Scale (KFSS) was correlated with several inflammatory markers in 38
      patients with MS (16 relapsing-remitting [RR; 7 of whom had benign MS), 9
      secondary progressive [SP], 13 primary progressive [PP]). The markers included
      daily urinary neopterin excretion, a marker of interferon-gamma-activated
      macrophage activity, and serum C-reactive protein (CRP) and soluble intercellular
      adhesion molecule-1 (sICAM-1) levels. Urinary neopterin excretion was measured
      daily for 2 weeks. RESULTS: No correlation was found between urinary neopterin
      excretion, CRP, or sICAM-1 and the fatigue scores. However, patients with a
      raised serum CRP level had higher KFSS, but not FQS, scores than patients with
      normal CRP levels (KFSS, 50 +/- 8 vs 41 +/- 14, p = 0.05; FQS, 13 +/- 4 vs 11 +/-
      5, p = NS). When assessed using the FQS, patients with RR and SP MS were more
      fatigued than patients with PP MS (RR = 12.5 [4 to 23] vs SP = 13 [8 to 18] vs PP
      = 9 [7 to 14], p = 0.02). The patients with benign MS were as fatigued as
      patients with nonbenign disease. CONCLUSION: The pathogenesis of fatigue in MS is
      complex and does not appear to be directly related to systemic markers of
      inflammatory disease activity. Interestingly, patients with PP MS were less
      fatigued than patients with RR disease.

PMID- 11524479
TI  - Differing effects of IFN beta vs IFN gamma in MS: gene expression in cultured
      astrocytes.
AB  - BACKGROUND: Recent clinical trials indicate that interferon-beta (IFN beta) is
      effective in reducing exacerbations in relapsing-remitting MS, whereas IFN gamma
      provokes acute relapses. However, the molecular mechanisms underlying the
      beneficial effects of IFN beta and the detrimental effects of IFN gamma in MS
      remain to be characterized. Previously, the authors showed that IFN beta
      inhibited IFN gamma-induced major histocompatibility complex (MHC) class II
      expression on astrocytes. OBJECTIVE: To clarify the gene expression profile in
      cultured fetal human astrocytes after exposure to IFN beta, IFN gamma, or IFN
      beta plus IFN gamma. METHODS: Astrocytes were incubated for 24 hours in the
      culture medium with or without inclusion of 50 ng/mL recombinant human IFN beta,
      IFN gamma, or both. The gene expression profile was studied by analyzing a cDNA
      expression array containing clones of various functional classes. RESULTS: Among
      1,185 clones examined, the expression of six distinct genes was markedly induced
      after IFN treatment. Northern blot analysis verified a significant up-regulation
      of mRNA for interferon regulatory factor-7 (IRF-7) and pleiotrophin predominantly
      in astrocytes treated with IFN beta, both IRF-1 and intercellular adhesion
      molecule-1 mRNA mainly in astrocytes treated with IFN gamma, and signal
      transducer and activator of transcription-1 alpha and MHC class I HLA-C mRNA
      equally in astrocytes exposed to either type of IFN. In contrast, the treatment
      of astrocytes with either IFN beta or IFN gamma did not alter the levels of
      expression of mRNA for brain-derived neurotrophic factor, 27-kd heat shock
      protein, prion protein, or defender against apoptotic cell death-1. No
      antagonistic action was observed between IFN beta and IFN gamma in the pattern of
      gene induction in astrocytes. CONCLUSION: A preferential induction of IRF-7 in
      IFN beta-treated astrocytes and a predominant expression of IRF-1 in IFN gamma
      exposed astrocytes might contribute to one of the molecular mechanisms underlying
      the clinically opposite effects of IFN beta and IFN gamma in MS.

PMID- 11524480
TI  - Miller Fisher syndrome and Haemophilus influenzae infection.
AB  - OBJECTIVE: To examine the association between Miller Fisher syndrome (MFS) and
      antecedent Haemophilus influenzae infection. BACKGROUND: Little is known about
      agents in prior respiratory tract infection of MFS, whereas antecedent upper
      respiratory symptoms are frequent. H. influenzae is a major pathogen that can
      cause human respiratory tract infection. METHODS: The authors used ELISA to
      detect serum antibody against the bacterium in 70 consecutive patients with MFS
      and 110 with Guillain-Barre syndrome (GBS). RESULTS: Serum anti-H. influenzae IgG
      and IgM antibody activities were significantly higher in the MFS group than in
      age- and sex-matched patients with other neurologic diseases (n = 62) and normal
      control subjects (n = 82). The GBS group showed no significant increase in any
      class of antibody activities compared with control groups. Serologic evidence of
      recent infection was found in five (7%) of the patients with MFS and two (2%) of
      110 patients with GBS, all of whom had a history of antecedent respiratory tract
      infection. They frequently showed ophthalmoplegia, but other neurologic features
      were not remarkable. Serum anti-GQ1b IgG antibody that had cross-reactivity with
      GT1a ganglioside was detected in six of these seven patients. Thin-layer
      chromatography with immunostaining showed that serum IgG from H. influenzae
      seropositive patients with high anti-GQ1b and anti-GT1a IgG antibody titers bound
      to the lipopolysaccharide fraction extracted from the type b H. influenzae
      serostrain. These bands were also stained by anti-GT1a monoclonal antibody
      (GMR11), indicating that the lipopolysaccharide bears the GT1a epitope.
      CONCLUSIONS: These findings point to H. influenzae being an agent associated with
      MFS. Epitopic overlap between H. influenzae and human nerve tissue may be
      involved in the development of MFS much as GBS is associated with Campylobacter
      jejuni enteritis.

PMID- 11524481
TI  - Ischemic stroke outcome: racial differences in the trial of danaparoid in acute
      stroke (TOAST).
AB  - OBJECTIVE: To determine racial differences in baseline stroke risk factors and
      other measures in the Trial of ORG 10172 in Acute Stroke Therapy (TOAST).
      Differences in these factors could influence response to acute stroke therapy and
      overall stroke outcome. METHODS: The authors compared baseline demographic,
      medical, stroke, physical examination, CT, laboratory, and neurologic factors
      among 292 African-American and 801 white patients who enrolled in the TOAST
      study. TOAST compared danaparoid (ORG 10172) with placebo among acute ischemic
      stroke patients who were treated within 24 hours of stroke onset. RESULTS:
      African-Americans were younger and more frequently had hypertension, diabetes
      mellitus, congestive heart failure, and prior strokes. In addition, African
      Americans had higher mean diastolic blood pressure, more lacunar strokes, and
      more severe prestroke disability. There were no significant differences between
      African-Americans and white patients in outcomes at 7 days, overall number of
      adverse experiences, or occurrence of serious bleeds or hemorrhagic
      transformations. However, there was a trend toward a higher rate of favorable
      outcomes in white patients at 7 days. There was no significant difference in very
      favorable outcome at 3 months between African-American and white patients, but
      significantly more white patients had favorable outcome at 3 months. CONCLUSION:
      Although African-Americans possess a number of factors that should predict higher
      rates of poor stroke outcome after acute therapy, they have the capacity to
      respond similarly to white patients after acute stroke therapy. Perhaps younger
      age and presence of lacunar infarction are stronger predictors of good outcomes
      than was appreciated previously.

PMID- 11524482
TI  - Effect of food on the bioavailability of 100-mg dilantin Kapseals.
AB  - The authors examined the effect of food on the bioavailability of Dilantin
      Kapseals in a nonblinded, single 100-mg dose, randomized, crossover trial. Drug
      was administered after an 8-hour fast and after a high-fat meal. Differences in
      mean dietary state values were +6% for maximum concentrations (C(max)) and -2%
      for area under the curve. Associated 90% CI were within US Food and Drug
      Administration criteria, confirming the absence of a food effect. Thus, patients
      may take 100-mg Dilantin Kapseals without regard to meals.

PMID- 11524483
TI  - Painful auras in focal epilepsy.
AB  - The authors studied the localizing or lateralizing value of painful epileptic
      auras in 25 patients with focal epilepsy. Painful auras were seen in 4.1%
      patients with focal epilepsy arising from temporal, frontal, perirolandic, or
      parieto-occipital regions. Abdominal pain was present in 5% of all abdominal
      auras in temporal lobe epilepsy and 50% of all abdominal auras in frontal lobe
      epilepsy. In perirolandic epilepsy, painful somatosensory auras were lateralized
      contralateral to the epileptic hemisphere but not consistently in temporal lobe
      epilepsy.

PMID- 11524484
TI  - Nav1.1 mutations cause febrile seizures associated with afebrile partial
      seizures.
AB  - Recent evidence has suggested that the neuronal voltage-gated sodium channel
      alpha(1)-subunit gene (Na(v)1.1: SCN1A) is responsible for generalized epilepsy
      with febrile seizures plus (GEFS+2). Here the authors report two novel disease
      mutations of Na(v)1.1 in patients with febrile seizures associated with afebrile
      partial seizures. One is a Val1428Ala substitution in the pore-forming region,
      and the other is Ala1685Val in the transmembrane helix. These results support the
      previous findings and contribute to the reliable diagnosis of epilepsy.

PMID- 11524485
TI  - Prolonged cortical silent period after transcranial magnetic stimulation in
      generalized epilepsy.
AB  - Transcranial magnetic stimulation (TMS) produces a cortical silent period (CSP)
      during a voluntary contraction. The duration of the CSP was used to assess the
      level of intracortical inhibition in patients with untreated idiopathic
      generalized epilepsy (IGE). Mean CSP duration was assessed at three TMS stimuli
      in 21 patients with IGE compared with 19 normal control subjects. Mean CSP
      duration was increased at all stimulus intensities, indicating that intracortical
      inhibition is increased in patients with IGE.

PMID- 11524486
TI  - Juvenile Huntington's disease presenting as progressive myoclonic epilepsy.
AB  - A 9-year-old girl, who had no family history of neurologic diseases in the first
      degree relatives, had a 3-year history of progressive myoclonus epilepsy (PME). A
      thorough laboratory investigation was normal. As two sisters of her paternal
      grandmother were said to have Huntington's disease (HD), the authors looked for
      HD and found a CAG repeat expansion of 115 repeats. This diagnosis should be
      considered in addition to other causes in patients with PME. Moreover, the
      current case further supports the notion that HD should be considered even when a
      family history is not obvious.

PMID- 11524487
TI  - Stereotyped stepping associated with lesions in the bilateral medial
      frontoparietal cortices.
AB  - The location of higher locomotion centers in humans is not well defined. The
      authors describe stereotyped bipedal stepping movement in a patient with
      meningoencephalitis with necrotic lesions localized mainly in the bilateral
      medial frontoparietal cortices. The patient intermittently showed stereotyped
      stepping in the supine position during a stuporous state. The stereotyped
      stepping in this patient offers clinical evidence indicating the presence of a
      higher locomotion center in medial frontoparietal cortex.

PMID- 11524488
TI  - Progression of impairment in patients with vascular cognitive impairment without
      dementia.
AB  - Little is known about progression, short of dementia, in vascular cognitive
      impairment. In the Canadian Study of Health and Aging, 149 participants (79.3 +/-
      6.7 years; 61% women) were found to have vascular cognitive impairment, no
      dementia (CIND). After 5 years, 77 participants (52%) had died and 58 (46%) had
      developed dementia. Women were at greater risk of dementia (OR 2.1, 1.0 to 4.5).
      Of 32 participants alive without dementia, cognition had deteriorated in seven
      and improved in four. Half of those with vascular CIND developed dementia within
      5 years, suggesting a target for preventive interventions.

PMID- 11524489
TI  - Primary central nervous system T-cell lymphoma.
AB  - Most primary CNS lymphomas (PCNSL) are B-cell neoplasms; T-cell lymphomas are
      quite rare. The authors report two young patients with T-cell PCNSL who had a
      complete response to chemo- and radiotherapy but developed recurrent disease and
      died 11 and 13 months from diagnosis. The prognosis of T-cell PCNSL may be worse
      than that of comparable B-cell tumors.

PMID- 11524490
TI  - Response to cancer therapy in a patient with a paraneoplastic choreiform
      disorder.
AB  - The authors report a patient with chorea and multifocal neurologic abnormalities
      associated with a small-cell lung carcinoma. A previously unreported antibody
      directed at a 76-kD neuronal protein antigen was identified in both serum and
      CSF. Antitumor treatment resulted in dramatic and sustained clinical neurologic
      and serologic responses.

PMID- 11524491
TI  - 14-3-3 protein in the CSF as prognostic marker in early multiple sclerosis.
AB  - Axonal damage probably occurs early in the evolution of MS. Five of 38 (13%)
      patients had a positive assay for the neuronal 14-3-3 protein in the CSF obtained
      at the first clinically isolated syndrome suggestive of MS. A positive 14-3-3
      assay was the only independent predictor for a shorter time to conversion to
      clinical definite MS (risk ratio 4.1; 95% CI 1.1 to 15) and to reach an Expanded
      Disability Status Scale (EDSS) > or =2 at the end of follow-up (odds ratio 14.8;
      95% CI 2.86 to 76.8). The detection of the 14-3-3 protein in the CSF at the first
      neurologic event suggestive of MS may be a useful predictor of short-term
      evolution.

PMID- 11524492
TI  - Diagnosis of HAM/TSP based on CSF proviral HTLV-I DNA and HTLV-I antibody index.
AB  - The contribution of human T-cell lymphotropic virus (HTLV-I) DNA by PCR in CSF
      and the intrathecal synthesis of antibodies to HTLV-I by the antibody index (AI)
      to the diagnosis of HTLV-1-associated myelopathy (HAM)/tropical spastic
      paraparesis (TSP) were evaluated. Cases of spastic paraparesis compatible with
      HAM/TSP had increased AI for HTLV-I (60/73) and HTLV-I proviral sequences in CSF
      (25/27). Among 27 patients with other neurologic diseases, three had increased AI
      and another three had positive HTLV-I DNA in CSF. Thus, the combination of PCR
      for proviral DNA and AI for HTLV-I in CSF provides consistent criteria for the
      diagnosis of HAM/TSP.

PMID- 11524493
TI  - Quantitation of 14-3-3 and neuron-specific enolase proteins in CSF in Creutzfeldt
      Jakob disease.
AB  - CSF 14-3-3 and neuron-specific enolase (NSE) proteins were quantitated from
      patients who had Creutzfeldt-Jakob disease (CJD) or other rapidly dementing
      disorders initially considered to be CJD. Thirty-one patients were diagnosed as
      having CJD among 152 studied. CSF 14-3-3 values more than 8 ng/mL correlated with
      CJD. CSF NSE values less than 30 ng/mL and 14-3-3 values less than 8 ng/mL made a
      diagnosis of CJD unlikely, but did not exclude it.

PMID- 11524494
TI  - Glatiramer acetate reduces the proportion of new MS lesions evolving into "black
      holes".
AB  - The authors evaluated whether glatiramer acetate (GA) modifies the severity of
      tissue damage in 1,722 new lesions from 239 patients with MS enrolled in a
      placebo-controlled trial monitored with monthly cerebral MRI. The percentage of
      new lesions that evolved into "black holes" was lower in GA-treated than in
      placebo patients on scans at 7 (18.9 and 26.3%; p = 0.04) and 8 (15.6 and 31.4%;
      p = 0.002) months after lesion appearance. GA has a favorable effect on tissue
      disruption in MS lesions once they are formed.

PMID- 11524495
TI  - Tongue atrophy in facioscapulohumeral muscular dystrophy.
AB  - Involvement of the lingual muscle is considered one of the exclusion criteria of
      facioscapulohumeral muscular dystrophy (FSHD). In a series of 151 Japanese
      patients with 4q35-FSHD, seven patients (4.6%) had tongue atrophy with abnormal
      MRI findings and typical myogenic patterns of electromyography. All seven
      patients belong to a group of early-onset FSHD with large gene deletions on
      chromosome 4q35. Our result suggests that the patients with 4q35-FSHD could have
      myopathic tongue atrophy.

PMID- 11524496
TI  - Anti-Gal-C antibodies in GBS subsequent to mycoplasma infection: evidence of
      molecular mimicry.
AB  - The authors previously reported the presence of antibody against
      galactocerebroside (Gal-C) in sera from patients with Guillain-Barre syndrome
      subsequent to Mycoplasma pneumoniae infection. Anti-Gal-C antibody activities in
      these sera were inhibited specifically by the M. pneumoniae reagent. A rabbit
      anti-Gal-C antibody recognized several glycolipids in M. pneumoniae. These data
      show that a Gal-C-like structure is present in M. pneumoniae, indicative of
      molecular mimicry between a major myelin glycolipid, Gal-C, and M. pneumoniae.

PMID- 11524497
TI  - Oral tendency due to frontal lobe lesion.

PMID- 11524498
TI  - Asystole induced by edrophonium following beta blockade.

PMID- 11524499
TI  - Neurolymphomatosis of the lumbar plexus: high-resolution MR neurography findings.

PMID- 11524500
TI  - Natural history of an incidentally discovered spinal dural arteriovenous fistula.

PMID- 11524501
TI  - Cerebral ergotism under treatment with ergotamine and ritonavir.

PMID- 11524502
TI  - Developmental venous anomaly of the pons.

PMID- 11524503
TI  - Continuous vertigo and spontaneous nystagmus due to canalolithiasis of the
      horizontal canal.

PMID- 11524504
TI  - MRI identification of early white matter injury in anoxic-ischemic
      encephalopathy.

PMID- 11524505
TI  - A multicenter assessment of dopamine transporter imaging with DOPASCAN/SPECT in
      parkinsonism.

PMID- 11524506
TI  - Failure to detect Chlamydia pneumoniae in the central nervous system of patients
      with MS.

PMID- 11524507
TI  - Olanzapine and clozapine: comparative effects on motor function in hallucinating
      PD patients.

PMID- 11524509
TI  - Tuskegee: could it happen again?

PMID- 11524510
TI  - Getting our journals to developing countries.

PMID- 11524511
TI  - Retinal astrocytic hamartoma.

PMID- 11524512
TI  - Calciphylaxis.
AB  - The phenomenon of calciphylaxis is rare, but potentially fatal. It has been
      recognised for a long time in patients with chronic renal failure with secondary
      hyperparathyroidism. Disturbed calcium and phosphate metabolism can result in
      painful necrosis of skin, subcutaneous tissue and acral gangrene. Appearance of
      the lesions is distinctive but the pathogenesis remains uncertain. The beneficial
      effects of parathyroidectomy are controversial. However, correction of
      hyperphosphataemia or occasionally hypercalcaemia is imperative. Fulminant sepsis
      as a consequence of secondary infection of necrotic and gangrenous tissue is a
      frequent cause of patient morbidity and mortality.

PMID- 11524513
TI  - Clinical implications of the specialised B cell response to polysaccharide
      encapsulated pathogens.

PMID- 11524515
TI  - Prognostic value of stress echocardiography in women with high (> or = 80%)
      probability of coronary artery disease.
AB  - OBJECTIVE: To assess the prognostic significance of stress echocardiography in
      women with a high probability of coronary artery disease (CAD). SETTING:
      Secondary and tertiary cardiology unit at a university teaching hospital.
      PARTICIPANTS: A total of 135 women (mean (SD) age 63 (9) years) with pre-test
      probability of CAD > or = 80% were selected from a database of patients
      investigated by treadmill or dobutamine stress echocardiography between 1995 and
      1998. MAIN OUTCOME MEASURES: Patients were followed up for occurrence of
      subsequent cardiac events (cardiac death, myocardial infarction, admission with
      unstable angina, and revascularisation) using a structured telephone interview
      and case note review. RESULTS: Each patient had between two and seven (mean 3.5)
      CAD risk factors and pre-test probability of CAD > or = 80%. Ninety three
      patients (68.9%) had negative stress echocardiography. Mean (SD) follow up was
      20.1 (8.5) months. There were six events in the positive stress echocardiography
      group (two cardiac deaths, one unstable angina, three revascularisations), and
      one event in the negative stress echocardiography group. Cox regression analysis
      showed positive stress echocardiography (p = 0.02) and age (p = 0.03) to be the
      only univariate predictors and positive stress echocardiography to be the only
      independent predictor of future cardiac events (relative risk 8.9, confidence
      interval 1.0 to 76.5, p = 0.04). Cumulative event free survival to 38 months was
      98% in the negative stress echocardiography and 50.7% in the positive stress
      echocardiography groups. CONCLUSION: In women with high pre-test likelihood of
      CAD: (1) negative stress echocardiography identifies a subgroup with low risk of
      cardiac events who do not require further invasive investigation and (2) positive
      stress echocardiography identifies a subgroup with increased risk of subsequent
      cardiac events.

PMID- 11524514
TI  - Hyperekplexia in neonates.
AB  - Hyperekplexia (startle disease) is a rare non-epileptic disorder characterised by
      an exaggerated persistent startle reaction to unexpected auditory, somatosensory
      and visual stimuli, generalised muscular rigidity, and nocturnal myoclonus. The
      genetic basis is a mutation usually of the arginine residue 271 leading to
      neuronal hyperexcitability by impairing glycinergic inhibition. Hyperekplexia is
      usually familial, most often autosomal dominant with complete penetrance and
      variable expression. It can present in fetal life as abnormal intrauterine
      movements, or later at any time from the neonatal period to adulthood. Early
      manifestations include abnormal responses to unexpected auditory, visual, and
      somatosensory stimuli such as sustained tonic spasm, exaggerated startle
      response, and fetal posture with clenched fists and anxious stare. The tonic
      spasms may mimic generalised tonic seizures, leading to apnoea and death.
      Consistent generalised flexor spasm in response to tapping of the nasal bridge
      (without habituation) is the clinical hallmark of hyperekplexia.
      Electroencephalography may show fast spikes initially during the tonic spasms,
      followed by slowing of background activity with eventual flattening corresponding
      to the phase of apnoea bradycardia and cyanosis. Electromyography shows a
      characteristic almost permanent muscular activity with periods of electrical
      quietness. Nerve conduction velocity is normal. No specific computed tomography
      findings have been reported yet. Clonazepam, a gamma aminobutyric acid (GABA)
      receptor agonist, is the treatment of choice for hypertonia and apnoeic episodes.
      It, however, may not influence the degree of stiffness significantly. A simple
      manoeuvre like forced flexion of the head and legs towards the trunk is known to
      be life saving when prolonged stiffness impedes respiration.

PMID- 11524517
TI  - Thiamine deficiency in patients with B-chronic lymphocytic leukaemia: a pilot
      study.
AB  - Malignancy associated primary thiamine deficiency has been documented in several
      experimental tumours, sporadic clinical case reports, and in a number of patients
      with fast growing haematological malignancies. Thiamine status was assessed
      prospectively in 14 untreated B-chronic lymphocytic leukaemia (CLL) patients, and
      in 14 age matched control patients with non-malignant disease. Patients with any
      known cause of absolute, relative, or functional thiamine deficiency were
      excluded. High (>15%) thiamine pyrophosphate effect (TPPE), indicating thiamine
      deficiency, was found in five out of 14 CLL patients (35.7%) and in none of the
      controls (p=0.057). Mean (SD) TPPE in the thiamine deficient patients group was
      21.6 (3.4)%. In all the patients, thiamine deficiency was subclinical. No
      correlates for the thiamine deficiency have been found save for an increment of
      more than 20% in the total leucocyte count over the preceding three months, which
      was found in all five thiamine deficient patients compared with only one of the
      nine non-thiamine deficient CLL patients. Thus, CLL patients may be prone to
      develop primary thiamine deficiency possibly promoted by the increased leucocytes
      span, which may increase thiamine consumption. Since even subclinical thiamine
      deficiency may be detrimental to the patient's clinical course, and in view of
      the theoretical danger of thiamine promoted tumour cell proliferation, further
      large scale studies are warranted to confirm this observation, and to elucidate
      the issue of thiamine supplementation to CLL patients.

PMID- 11524516
TI  - Why do some people look older than they should?
AB  - BACKGROUND: As a component of studies on biological age, the age of subjects from
      their appearance (perceived age) was estimated. OBJECTIVE: To determine the
      factors associated with looking older. METHODS: Cross sectional study of London
      civil servants (318 men, 129 women) in the Department of the Environment study.
      Perceived age was recorded by an observer and the difference between this age and
      chronological age was analysed according to 20 different variables. RESULTS: Men
      had an average perceived age of 0.37 years older than their actual age and women
      a perceived age of 0.54 years younger. In men, looking older was related to
      greying of the hair, grade of arcus senilis, and grade of baldness. Less
      expected, looking older was positively related to total serum cholesterol
      (p=0.03) and blood haemoglobin (p<0.01). In women, looking older was related to
      greying of the hair, positively to blood erythrocyte sedimentation rate (ESR),
      and negatively to serum bilirubin (p=0.01). Looking older was not related to
      alcohol consumption, employment grade, serum high density lipoprotein
      cholesterol, glucose, albumin, and calcium in either sex. CONCLUSION: The
      relationships between looking older and total cholesterol and haemoglobin in men
      and ESR and bilirubin in women, require further investigation.

PMID- 11524518
TI  - Specialist follow up of patients before end stage renal failure and its
      relationship to survival on dialysis.
AB  - The high mortality rate of patients with end stage renal failure (ESRF) treated
      by dialysis is determined principally by irreversible factors such as age and
      comorbidity. In this single centre retrospective study of all 1260 ESRF patients
      who started dialysis between 1980 and 1999 it has been demonstrated that a short
      duration of specialist predialysis follow up is associated with a worse long term
      outcome on dialysis. Kaplan-Meier survival curves were plotted according to
      duration of predialysis follow up (group A, < or = 90 days; group B > 90 days),
      censoring for first transplant, and compared using a log rank test. Differences
      between groups were examined using an unpaired t test. Cox regression analysis
      was performed to examine the influence of selected variables on survival. Group A
      had the worst mortality (survival proportions of 87%, 74%, and 31% in A and 94%,
      87%, and 55% in B at four months, one year, and five years respectively, p <
      0.001). The increased risk of death was seen principally during the first few
      months of dialysis. ESRF associated with systemic disease was more prevalent in
      A. There were small but significant differences in predialysis clinical data,
      including age and serum albumin (p < 0.001). Fewer patients in A were suitable
      for transplant listing (p < 0.01). In the regression analysis, age, diabetes,
      predialysis serum albumin, suitability for transplant work-up and listing
      ("transplantability"), and the interval between referral and dialysis were
      significant predictors of survival. In summary, this study strengthens the
      previously reported association between late referral of ESRF patients and
      subsequent poor survival on dialysis. This important message is relevant to all
      potential referring physicians.

PMID- 11524519
TI  - Primary neuroleptospirosis.
AB  - Leptospirosis is an important zoonosis of worldwide distribution. It is uncommon
      for leptospirosis to present as a primary neurological disease. In this study of
      patients who presented with an acute neurological disease, and who were
      subsequently found to have leptospirosis, aseptic meningitis was the commonest
      manifestation. The other presentations were myeloradiculopathy, myelopathy,
      Guillain-Barre syndrome-like presentation, meningoencephalitis, intracerebral
      bleed, cerebellar dysfunction, iridocyclitis, and tremor/rigidity. Treatment
      consists of antibiotics, crystalline penicillin being the drug of choice, which
      reduces the course of illness if given early. The role of steroids is
      controversial. The prognosis after primary neuroleptospirosis is generally good
      but altered sensorium and seizures herald a worse prognosis.

PMID- 11524520
TI  - Changing thyroid status related to pregnancy.
AB  - A case of post-thyroidectomy hypothyroidism is reported. The patient became
      euthyroid in three consecutive pregnancies, reverting to hypothyroid within three
      months of delivery on each occasion. The alteration in thyroid status is
      attributed to pregnancy related changes in antibody titres, though the laboratory
      data to confirm this are not available.

PMID- 11524521
TI  - "Do we murder Mary to save Jodie?" An ethical analysis of the separation of the
      Manchester conjoined twins.

PMID- 11524522
TI  - A case of venous thrombosis.

PMID- 11524523
TI  - An elderly woman with chronic knee pain and abnormal chest radiography.

PMID- 11524524
TI  - Stridor, malaise, and visual loss in a woman from Sierra Leone.

PMID- 11524525
TI  - Abdominal pain in an intrauterine contraceptive device user.

PMID- 11524526
TI  - Abdominal pain after trauma in a young man.

PMID- 11524527
TI  - Transient ST segment changes mimicking early repolarisation phenomenon in a
      patient with angina at rest.

PMID- 11524528
TI  - Two diagnoses from one electrocardiogram.

PMID- 11524529
TI  - An unusual intra-abdominal tumour.

PMID- 11524546
TI  - Faith in stem cells.

PMID- 11524547
TI  - Novel_target.com.

PMID- 11524548
TI  - Chemotherapy and herceptin for HER2(+) metastatic breast cancer: the best drug?

PMID- 11524549
TI  - Hematologic malignancies.
AB  - This article reviews highlights in the field of hematologic malignancies
      presented at the 2001 annual meeting of the American Society of Clinical
      Oncology. Targeted therapies continue to proceed from the laboratory to the
      clinic. Monoclonal antibody-based therapies predominate, and further data on
      radioimmunoconjugates (RICs) (tositumomab and Iodine 131 tositumomab [Bexxar] and
      ibritumomab tiuxetan [Zevalin]) are presented. Both agents have high response
      rates in relapsed B-cell non-Hodgkin's lymphoma (NHL). Results from the first
      trial directly comparing an RIC (Zevalin) to an unconjugated antibody (rituximab)
      are presented. A novel application of RIC therapy as part of high-dose therapy
      for mantle cell NHL is described. A new fusion toxin, BL22, targets the CD22
      antigen and shows marked activity in the treatment of hairy cell leukemia.
      Similarly, the Hu1D10 monoclonal antibody has activity in B-cell NHL and might
      have a relatively unique mechanism of action. Finally, advances in the treatment
      of mucositis are described. These abstracts all describe therapies derived from
      our enhanced understanding of tumor immunology and molecular biology.

PMID- 11524550
TI  - Ovarian cancer.
AB  - Ovarian cancer remains the most lethal gynecologic malignancy in women in the
      United States. Studies from this year's American Society of Clinical Oncology
      more clearly defined the role of chemotherapy in women with early stage disease
      and now suggest that essentially all women with invasive disease should receive
      chemotherapy that contains carboplatin. Studies in women with advanced disease
      continue to support the use of carboplatin and paclitaxel in the treatment of
      women with newly diagnosed disease although early data suggest that carboplatin
      and docetaxel might be an acceptable alternative. Platinum-resistant disease
      remains a therapeutic challenge. Small molecules that inhibit the function of the
      epidermal growth factor receptor, such as OSI-774, and novel classes of
      chemotherapeutic agents, including the acylfulvene MGI-114 and epothilone B and
      its analogue, BMS247550, all warrant further study in this disease.

PMID- 11524551
TI  - Sarcoma.
AB  - ASCO 2001 was a banner year for innovative systemic therapy for sarcomas.
      Imatinib mesylate (STI571, Gleevec) shows clear activity not only in chronic
      myelogenous leukemia, for which the drug received Food and Drug Administration
      approval, but also in gastrointestinal stromal tumors as well, by virtue of
      imatinib mesylate binding to the abl, kit, and platelet-derived growth factor
      receptor tyrosine kinases. Ecteinascidin-743 (ET-743) demonstrates activity
      against a fraction of other soft-tissue sarcomas. Gemcitabine-based regimens show
      at least some activity against a subset of soft-tissue sarcomas. Given the lack
      of new agents for sarcoma therapy since the development of ifosfamide, these
      studies give hope that the term "effective systemic therapy for sarcoma" might
      become a reality.

PMID- 11524552
TI  - Breast cancer.
AB  - Several interesting aspects of breast cancer were covered at this year's American
      Society of Clinical Oncology meeting. Sentinel lymph node (SN) mapping is now in
      widespread use, in concert with the general trend toward trying to decrease the
      morbidity of breast cancer surgery. With every advance, however, comes new
      challenges, and there was a timely presentation from Giuliano's group addressing
      the controversial issue of how to interpret the presence of cells in the SN seen
      only with keratin stains but not by routine hematoxylin and eosin stains. Two
      abstracts addressed the issue of whether for certain women with invasive breast
      cancer radiation therapy could be omitted after lumpectomy. Another interesting
      topic related to hormonal issues in the adjuvant treatment of premenopausal
      women. An analysis from the ZIPP-TRIAL reported on bone marrow density studies in
      young women given two years of ovarian suppression in the adjuvant setting: it
      seems that the loss of bone density may be reversible and, more interestingly,
      may be prevented with concurrent tamoxifen. Two other presentations looked at the
      prognostic significance of drug-induced amenorrhea in young women treated with
      adjuvant chemotherapy and at the efficacy of ovarian suppression during
      chemotherapy in preserving fertility. In an unpublicized presentation, Mary
      Claire King presented very interesting results from the National Surgical
      Adjuvant Breast and Bowel Project Breast Cancer Prevention Trial suggesting that
      tamoxifen may be an effective chemopreventive drug for women with BRCA2, but not
      BRCA1, mutations. Two important presentations re-analyzed the outcome of the
      pivotal trials using Herceptin to treat metastatic breast cancer and nicely show
      that FISH analysis of HER-2 overexpression is a more accurate indicator of
      response to Herceptin than immunohistochemical staining. Finally, there were two
      interesting presentations related to tamoxifen resistance which may be relevant
      clinically, pertaining to subsequent raloxifene use and the interaction of the
      estrogen receptor and EGF receptor pathways, respectively.

PMID- 11524553
TI  - Vinorelbine, epirubicin, and methotrexate (VEM) as primary treatment in locally
      advanced breast cancer.
AB  - PURPOSE: This phase II trial of VEM (vinorelbine + epirubicine + methotrexate) in
      the treatment of locally advanced breast cancer was conducted to obtain
      downstaging to allow surgery and breast conservation. PATIENTS AND METHODS: This
      multicenter study recruited 58 patients with locally advanced breast cancer (two
      patients ineligible); 56 were evaluable for response and tolerance. RESULTS:
      Downstaging was obtained in 77% of the patients with a pathological complete
      response (pCR) rate of 9%. At 33 months of follow-up, median survival has not
      been reached. Neutropenia grade 3-4 was reported in 31% of cycles with 3% of
      cycles with infection grade 3. Alopecia grade 3 was noticed for 71% of patients.
      CONCLUSION: VEM represents an effective regimen for patients with locally
      advanced breast cancer, allowing an important pCR. Moreover, this regimen appears
      to be particularly well tolerated.

PMID- 11524554
TI  - Hormone replacement in women with a history of breast cancer.
AB  - Estrogen used alone (estrogen replacement therapy [ERT]) or with the addition of
      progesterone (hormone replacement therapy [HRT]) is known to be effective in
      reducing menopausal symptoms including hot flashes, vaginal dryness and urinary
      symptoms. It has been traditionally contraindicated, however, in women with a
      previous diagnosis of breast cancer because of fear that it may increase the risk
      of recurrence. There are considerable basic scientific data but little
      methodologically strong observational data and none from randomized studies
      concerning the use of ERT in women with a prior diagnosis of breast cancer. From
      our knowledge of the physiology of breast cancer, however, estrogen and/or
      progestational agents should be used with caution in women with a previous
      diagnosis of breast cancer. There are currently many alternatives to ERT/HRT in
      the prevention of menopausal symptoms such as vitamin E, clonidine and selective
      serotonin reuptake inhibitor antidepressants such as venlafaxine. There are also
      a variety of other approaches to the prevention of osteoporosis and
      cardiovascular disease including bisphosphonates, diet, and exercise; and diet,
      exercise, and statins, respectively. Other suggested beneficial effects of
      estrogen such as colon cancer prevention can be approached by the use of aspirin
      or the non-steroidals. Several trials of ERT/HRT used for 2 years versus no
      therapy in menopausal women with a previous diagnosis of breast cancer are
      ongoing in Europe and Britain, and should give us stronger data as to the role of
      HRT in this setting.

PMID- 11524555
TI  - Pemetrexed disodium: a novel antifolate clinically active against multiple solid
      tumors.
AB  - Pemetrexed disodium (ALIMTA), "pemetrexed") is a novel, multi-targeted antifolate
      that has demonstrated promising clinical activity in a wide variety of solid
      tumors, including non-small cell lung, breast, mesothelioma, colorectal,
      pancreatic, gastric, bladder, cervix, and head and neck. Pemetrexed inhibits
      multiple folate-dependent enzymes involved in both purine and pyrimidine
      synthesis including thymidylate synthase, dihydrofolate reductase, glycinamide
      ribonucleotide formyltransferase, and aminoimidazole carboxamide ribonucleotide
      formyltransferase. As a single agent, pemetrexed exhibits a moderate toxicity
      profile at a dose of 500 mg/m(2) by 10-minute infusion once every 21 days with
      myelosuppression being the dose-limiting toxicity. Folic acid added to the diet
      in preclinical studies reduced toxicities while maintaining antitumor activity.
      Based on this observation and clinical toxicities, folic acid and vitamin B(12)
      dietary supplementation has been recently introduced into all ongoing trials.
      Studies combining pemetrexed with other active chemotherapeutic agents
      demonstrate that these combination therapies may become important treatment
      regimens in a variety of cancer types. Currently, pemetrexed phase III trials are
      ongoing in mesothelioma and non-small cell lung cancer with future trials planned
      to explore this unique multitargeted antifolate.

PMID- 11524556
TI  - The molecular perspective: interferons.

PMID- 11524557
TI  - Adjuvant therapy of primary breast cancer: a review of key findings from the 7th
      international conference, St. Gallen, February 2001.
AB  - Breast cancer research has developed at a rapid pace over the last decades.
      Recent discoveries promise to provide individualized treatment options, increased
      long-term survival for women with breast cancer, and the possibility of moving
      toward curative intent in the treatment of advanced breast cancer. Age, race,
      tumor size, histological tumor type, axillary nodal status, standardized
      pathological grade, and hormone-receptor status are accepted as established
      prognostic and/or predictive factors for selection of systemic adjuvant treatment
      of breast cancer. The role of other promising new factors, such as p53 mutations,
      HER-2 status, plasminogen activator system, histological evidence of vascular
      invasion, and quantitative parameters of angiogenesis will be determined in
      ongoing prospective studies. Currently, 5 years' treatment with adjuvant
      tamoxifen in women with hormone-positive receptor status, is regarded as the
      optimal duration of treatment. Long-term follow-up on the randomized trials will
      determine the added benefit of treatment beyond 5 years. Ovarian ablation has
      shown a reduction in recurrence and death, and the exact role and extent of
      adjuvant chemotherapy in premenopausal women with hormone-responsive tumors is
      under discussion. Combination hormonal and chemo-hormonal therapies are also
      being evaluated. There are no convincing data on the survival impact of tamoxifen
      as a preventative therapy for breast cancer: longer-term follow-up is required,
      and the planned meta-analyses in 2005 should help shed light on this issue.
      Statistically significant benefits have been observed with adjuvant chemotherapy
      (particularly with anthracycline-containing regimens in premenopausal women)
      versus no adjuvant chemotherapy. The optimal length of adjuvant
      anthracycline/cyclophosphamide (AC) regimens needs further evaluation as do
      randomized comparisons of AC to cyclophosphamide/ doxorubicin/5-fluorouracil (5
      FU) and cyclophosphamide/epirubicin/5-FU. Although taxanes promise to provide an
      additive benefit to adjuvant chemotherapy regimens, the Cancer and Leukemia Group
      B 9344 and the National Surgical Adjuvant Breast and Bowel Project B-28 studies
      evaluating paclitaxel in the adjuvant setting have not yet demonstrated
      statistically significant benefits on disease-free survival and overall survival.
      In the year 2000, all adjuvant therapy studies conducted by the Co-operative
      Groups in both node-negative and node-positive disease involve a taxane. High
      dose chemotherapy evaluations are still ongoing. The numerous prospective
      adjuvant therapy trials (hormonal; selective estrogen-receptor modulators;
      aromatase inhibitors; chemotherapy, involving
      anthracyclines/taxanes/platinum/trastuzumab; biological factors; elderly women
      (>70 years); high-risk patients; radiotherapy in 1-3 positive lymph nodes), and
      neoadjuvant studies might further define the chances to enhance cure rates in the
      treatment of primary breast cancer.

PMID- 11524558
TI  - Capitol report.

PMID- 11524559
TI  - Seven alternatives to evidence-based medicine.

PMID- 11524565
TI  - High-pressure protein crystallography (HPPX): instrumentation, methodology and
      results on lysozyme crystals.
AB  - A new set-up and associated methodology for the collection of angle-dispersive
      diffraction data from protein crystals submitted to high hydrostastic pressure
      have been developed on beamline ID30 at the ESRF. The instrument makes use of
      intense X-rays of ultra-short wavelength emitted by two collinear undulators, and
      combines a membrane-driven diamond-anvil cell mounted on a two-axis goniometer
      and an imaging-plate scanner. Sharp and clean diffraction pictures from
      tetragonal crystals of hen egg-white lysozyme (tHEWL) and orthorhombic crystals
      of bovine erythrocyte Cu, Zn superoxide dismutase (SOD) were recorded at room
      temperature and pressures up to 0.915 and 1.00 GPa, respectively. The
      compressibility of tHEWL was determined from unit-cell parameters determined at
      24 different pressures up to 0.915 GPa. High-pressure diffraction data sets from
      several crystals of tHEWL were collected and analyzed. Merging of data recorded
      on different crystals at 0.30 and 0.58 GPa produced two sets of structure
      amplitudes with good resolution, completeness, redundancy and R(sym) values. A
      third set at 0.69 GPa was of a similar quality except a lower completeness. The
      three structures have been refined. The pressure-induced loss of crystalline
      order in a tHEWL crystal beyond 0.82 GPa was captured through a series of
      diffraction pictures.

PMID- 11524575
TI  - Bistability dynamics in simulations of neural activity in high-extracellular
      potassium conditions.
AB  - Modulation of extracellular potassium concentration ([K](o)) has a profound
      impact on the excitability of neurons and neuronal networks. In the CA3 region of
      the rat hippocampus synchronized epileptiform bursts occur in conditions of
      increased [K](o). The dynamic nature of spontaneous neuronal firing in high
      [K](o) is therefore of interest. One particular interest is the potential
      presence of bistable behaviors such as the coexistence of stable repetitive
      firing and fixed rest potential states generated in individual cells by the
      elevation of [K](o). The dynamics of repetitive activity generated by increased
      [K](o) is investigated in a 19-compartment hippocampal pyramidal cell (HPC) model
      and a related two-compartment reduced HPC model. Results are compared with those
      for the Hodgkin-Huxley equations in similar conditions. For neural models, [K](o)
      changes are simulated as a shift in the potassium reversal potential (E(K)).
      Using phase resetting and bifurcation analysis techniques, all three models are
      shown to have specific regions of E(K) that result in bistability. For activity
      in bistable parameter regions, stimulus parameters are identified that switch
      high-potassium model behavior from repetitive firing to a quiescent state.
      Bistability in the HPC models is limited to a very small parameter region.
      Consequently, our results suggest that it is likely some HPCs in networks exposed
      to high [K](o) continue to burst such that a stable, quiescent network state does
      not exist. In [K](o) ranges where HPCs are not bistable, the population may still
      exhibit bistable behaviors where synchronous population events are reversibly
      annihilated by phase resetting pulses, suggesting the existence of a
      nonsynchronous network attractor.

PMID- 11524576
TI  - Do neocortical pyramidal neurons display stochastic resonance?
AB  - Neocortical pyramidal neurons in vivo are subject to an intense synaptic
      background activity that has a significant impact on various electrophysiological
      properties and dendritic integration. Using detailed biophysical models of a
      morphologically reconstructed neocortical pyramidal neuron, in which synaptic
      background activity was simulated according to recent measurements in cat
      parietal cortex in vivo, we show that the responsiveness of the cell to
      additional periodic subthreshold stimuli can be significantly enhanced through
      mechanisms similar to stochastic resonance. We compare several paradigms leading
      to stochastic resonance-like behavior, such as varying the strength or the
      correlation in the background activity. A new type of resonance-like behavior was
      obtained when the correlation was varied, in which case the responsiveness is
      sensitive to the statistics rather than the strength of the noise. We suggest
      that this type of resonance may be relevant to information processing in the
      cerebral cortex.

PMID- 11524577
TI  - Period doubling of calcium spike firing in a model of a Purkinje cell dendrite.
AB  - Recordings from cerebellar Purkinje cell dendrites have revealed that in response
      to sustained current injection, the cell firing pattern can move from tonic
      firing of Ca(2+) spikes to doublet firing and even to quadruplet firing or more
      complex firing. These firing patterns are not modified substantially if Na(+)
      currents are blocked. We show that the experimental results can be viewed as a
      slow transition of the neuronal dynamics through a period-doubling bifurcation.
      To further support this conclusion and to understand the underlying mechanism
      that leads to doublet firing, we develop and study a simple, one-compartment
      model of Purkinje cell dendrite. The neuron can also exhibit quadruplet and
      chaotic firing patterns that are similar to the firing patterns that some of the
      Purkinje cells exhibit experimentally. The effects of parameters such as
      temperature, applied current, and potassium reversal potential in the model
      resemble their effects in experiments. The model dynamics involve three time
      scales. Ca(2+)- dependent K(+) currents, with intermediate time scales, are
      responsible for the appearance of doublet firing, whereas a very slow
      hyperpolarizing current transfers the neuron from tonic to doublet firing. We use
      the fast-slow analysis to separate the effects of the three time scales. Fast
      slow analysis of the neuronal dynamics, with the activation variable of the very
      slow, hyperpolarizing current considered as a parameter, reveals that the
      transitions occurs via a cascade of period-doubling bifurcations of the fast and
      intermediate subsystem as this slow variable increases. We carry out another
      analysis, with the Ca(2+) concentration considered as a parameter, to investigate
      the conditions for the generation of doublet firing in systems with one effective
      variable with intermediate time scale, in which the rest state of the fast
      subsystem is terminated by a saddle-node bifurcation. We find that the scenario
      of period doubling in these systems can occur only if (1) the time scale of the
      intermediate variable (here, the decay rate of the calcium concentration) is slow
      enough in comparison with the interspike interval of the tonic firing at the
      transition but is not too slow and (2) there is a biostability of the fast
      subsystem of the spike-generating variables.

PMID- 11524578
TI  - Effects of neuromodulation in a cortical network model of object working memory
      dominated by recurrent inhibition.
AB  - Experimental evidence suggests that the maintenance of an item in working memory
      is achieved through persistent activity in selective neural assemblies of the
      cortex. To understand the mechanisms underlying this phenomenon, it is essential
      to investigate how persistent activity is affected by external inputs or
      neuromodulation. We have addressed these questions using a recurrent network
      model of object working memory. Recurrence is dominated by inhibition, although
      persistent activity is generated through recurrent excitation in small subsets of
      excitatory neurons. Our main findings are as follows. (1) Because of the strong
      feedback inhibition, persistent activity shows an inverted U shape as a function
      of increased external drive to the network. (2) A transient external excitation
      can switch off a network from a selective persistent state to its spontaneous
      state. (3) The maintenance of the sample stimulus in working memory is not
      affected by intervening stimuli (distractors) during the delay period, provided
      the stimulation intensity is not large. On the other hand, if stimulation
      intensity is large enough, distractors disrupt sample-related persistent
      activity, and the network is able to maintain a memory only of the last shown
      stimulus. (4) A concerted modulation of GABA(A) and NMDA conductances leads to a
      decrease of spontaneous activity but an increase of persistent activity; the
      enhanced signal-to-noise ratio is shown to increase the resistance of the network
      to distractors. (5) Two mechanisms are identified that produce an inverted U
      shaped dependence of persistent activity on modulation. The present study
      therefore points to several mechanisms that enhance the signal-to-noise ratio in
      working memory states. These mechanisms could be implemented in the prefrontal
      cortex by dopaminergic projections from the midbrain.

PMID- 11524580
TI  - Early contributions to the Johns Hopkins hospital by the "other" surgeon: John
      Shaw Billings.

PMID- 11524581
TI  - Laparoscopic versus open gastric bypass: a randomized study of outcomes, quality
      of life, and costs.
AB  - OBJECTIVE: To compare outcomes, quality of life (QOL), and costs of laparoscopic
      and open gastric bypass (GBP). SUMMARY BACKGROUND DATA: Laparoscopic GBP has been
      reported to be a safe and effective approach for the treatment of morbid obesity.
      The authors performed a prospective randomized trial to compare outcomes, QOL,
      and costs of laparoscopic GBP with those of open GBP. METHODS: From May 1999 to
      March 2001, 155 patients with a body mass index (BMI) of 40 to 60 kg/m2 were
      randomly assigned to undergo laparoscopic (n = 79) or open (n = 76) GBP. The two
      groups were similar in age, sex ratio, mean BMI, and comorbidities. Main outcome
      measures included operative time, estimated blood loss, length of hospital stay,
      operative complications, percentage of excess body weight loss, and time to
      return to activities of daily living and work. Changes in QOL were assessed using
      the SF-36 Health Survey and the bariatric analysis of reporting outcome system
      (BAROS). Operative and hospital costs of the two operations were also compared.
      RESULTS: There were no deaths in either group. Mean operative time was longer for
      laparoscopic GBP than for open GBP, but operative blood loss was less. Two (2.5%)
      of the 79 patients in the laparoscopic group required conversion to laparotomy.
      Median length of hospital stay was shorter for laparoscopic GBP patients (3 vs 4
      days). The rate of postoperative anastomotic leak was similar between groups.
      Wound-related complications such as infection (10.5 vs 1.3%) and incisional
      hernia (7.9 vs 0%) were more common after open GBP; late anastomotic stricture
      was less frequent after open GBP (2.6 vs 11.4%). Time to return to activities of
      daily living and work were shorter after laparoscopic GBP than after open GBP.
      Weight loss at 1 year was similar between groups. Preoperative SF-36 scores were
      similar between groups; however, at 1 month after surgery, laparoscopic patients
      had better physical conditioning, social functioning, general health, and less
      body pain than open GBP patients. At 6 months, the BAROS outcome was classified
      as good or better in 97% of laparoscopic GBP patients compared with 82% of open
      GBP patients. Operative costs were higher for laparoscopic GBP patients, but
      hospital costs were lower. CONCLUSIONS: Laparoscopic GBP is a safe and cost
      effective alternative to open GBP. Despite a longer operative time, patients
      undergoing laparoscopic GBP benefited from less blood loss, a shorter hospital
      stay, and faster convalescence. Laparoscopic GBP patients had comparable weight
      loss at 1 year but a more rapid improvement in QOL than open GBP patients. The
      higher initial operative costs for laparoscopic GBP were adequately offset by the
      lower hospital costs.

PMID- 11524582
TI  - Defining the optimal surgeon experience for breast cancer sentinel lymph node
      biopsy: a model for implementation of new surgical techniques.
AB  - OBJECTIVE: To determine the optimal experience required to minimize the false
      negative rate of sentinel lymph node (SLN) biopsy for breast cancer. SUMMARY
      BACKGROUND DATA: Before abandoning routine axillary dissection in favor of SLN
      biopsy for breast cancer, each surgeon and institution must document acceptable
      SLN identification and false-negative rates. Although some studies have examined
      the impact of individual surgeon experience on the SLN identification rate,
      minimal data exist to determine the optimal experience required to minimize the
      more crucial false-negative rate. METHODS: Analysis was performed of a large
      prospective multiinstitutional study involving 226 surgeons. SLN biopsy was
      performed using blue dye, radioactive colloid, or both. SLN biopsy was performed
      with completion axillary LN dissection in all patients. The impact of surgeon
      experience on the SLN identification and false-negative rates was examined.
      Logistic regression analysis was performed to evaluate independent factors in
      addition to surgeon experience associated with these outcomes. RESULTS: A total
      of 2,148 patients were enrolled in the study. Improvement in the SLN
      identification and false-negative rates was found after 20 cases had been
      performed. Multivariate analysis revealed that patient age, nonpalpable tumors,
      and injection of blue dye alone for SLN biopsy were independently associated with
      decreased SLN identification rates, whereas upper outer quadrant tumor location
      was the only factor associated with an increased false-negative rate.
      CONCLUSIONS: Surgeons should perform at least 20 SLN cases with acceptable
      results before abandoning routine axillary dissection. This study provides a
      model for surgeon training and experience that may be applicable to the
      implementation of other new surgical technologies.

PMID- 11524583
TI  - One hundred nine living donor liver transplants in adults and children: a single
      center experience.
AB  - OBJECTIVE: To summarize the evolution of a living donor liver transplant program
      and the authors' experience with 109 cases. SUMMARY BACKGROUND DATA: The authors'
      institution began to offer living donor liver transplants to children in 1993 and
      to adults in 1998. METHODS: Donors were healthy, ages 18 to 60 years, related or
      unrelated, and ABO-compatible (except in one case). Donor evaluation was
      thorough. Liver biopsy was performed for abnormal lipid profiles or a history of
      significant alcohol use, a body mass index more than 28, or suspected steatosis.
      Imaging studies included angiography, computed tomography, endoscopic retrograde
      cholangiopancreatography, and magnetic resonance imaging. Recipient evaluation
      and management were the same as for cadaveric transplant. RESULTS: After ABO
      screening, 136 potential donors were evaluated for 113 recipients; 23 donors
      withdrew for medical or personal reasons. Four donor surgeries were aborted; 109
      transplants were performed. Fifty children (18 years or younger) received 47 left
      lateral segments and 3 left lobes; 59 adults received 50 right lobes and 9 left
      lobes. The average donor hospital stay was 6 days. Two donors each required one
      unit of banked blood. Right lobe donors had three bile leaks from the cut surface
      of the liver; all resolved. Another right lobe donor had prolonged
      hyperbilirubinemia. Three donors had small bowel obstructions; two required
      operation. All donors are alive and well. The most common indications for
      transplant were biliary atresia in children (56%) and hepatitis C in adults
      (40%); 35.6% of adults had hepatocellular carcinoma. Biliary reconstructions in
      all children and 44 adults were with a Roux-en-Y hepaticojejunostomy; 15 adults
      had duct-to-duct anastomoses. The incidence of major vascular complications was
      12% in children and 11.8% in adult recipients. Children had three bile leaks (6%)
      and six (12%) biliary strictures. Adult patients had 14 (23.7%) bile leaks and 4
      (6.8%) biliary strictures. Patient and graft survival rates were 87.6% and 81%,
      respectively, at 1 year and 75.1% and 69.6% at 5 years. In children, patient and
      graft survival rates were 89.9% and 85.8%, respectively, at 1 year and 80.9% and
      78% at 5 years. In adults, patient and graft survival rates were 85.6% and 77%,
      respectively, at 1 year. CONCLUSION: Living donor liver transplantation has
      become an important option for our patients and has dramatically changed our
      approach to patients with liver failure. The donor surgery is safe and can be
      done with minimal complications. We expect that living donor liver transplants
      will represent more than 50% of our transplants within 3 years.

PMID- 11524584
TI  - Intraductal papillary mucinous neoplasms of the pancreas: an increasingly
      recognized clinicopathologic entity.
AB  - OBJECTIVE: To assess the authors' experience with intraductal papillary mucinous
      neoplasms of the pancreas (IPMNs). SUMMARY BACKGROUND DATA: Intraductal papillary
      mucinous neoplasms of the pancreas are being recognized with increasing
      frequency. METHODS: All patients who underwent pancreatic resection for an IPMN
      at the Johns Hopkins Hospital between January 1987 and December 2000 were
      studied. The data were compared with those of 702 concurrent patients with
      infiltrating ductal adenocarcinoma of the pancreas not associated with an IPMN
      resected by pancreaticoduodenectomy. RESULTS: In the 13-year time period, 60
      patients underwent pancreatic resection for IPMNs, with 40 patients undergoing
      resection in the past 3 years. Mean age at presentation was 67.4 +/- 1.4 years.
      The most common presenting symptom in patients with IPMNs was abdominal pain
      (59%). Most IPMNs were in the head of the pancreas or diffusely involved the
      gland, with 70% being resected via pancreaticoduodenectomy, 22% via total
      pancreatectomy, and 8% via distal pancreatectomy. Twenty-two patients (37%) had
      IPMNs with an associated infiltrating adenocarcinoma. In a subset of IPMNs
      immunohistochemically stained for the Dpc4 protein (n = 50), all of the
      intraductal or noninvasive components strongly expressed Dpc4, whereas 84% of
      associated infiltrating cancers expressed Dpc4. The 5-year survival rate for all
      patients with IPMNs (n = 60) was 57%. CONCLUSION: Intraductal papillary mucinous
      neoplasms represent a distinct clinicopathologic entity being recognized with
      increasing frequency. IPMNs are clinically, histologically, and genetically
      disparate from pancreatic ductal adenocarcinomas. The distinct clinical features,
      the presumably long in situ or noninvasive phase, and the good long-term survival
      of patients with IPMNs offer a unique opportunity for early diagnosis, curative
      resection, and further studies of the molecular genetics and natural history of
      these unusual neoplasms.

PMID- 11524585
TI  - Increasing incidence of midterm and long-term complications after endovascular
      graft repair of abdominal aortic aneurysms: a note of caution based on a 9-year
      experience.
AB  - OBJECTIVE: To analyze the late complications after endovascular graft repair of
      elective abdominal aortic aneurysms (AAAs) at the authors' institution since
      November 1992. SUMMARY BACKGROUND DATA: Recently, the use of endovascular grafts
      for the treatment of AAAs has increased dramatically. However, there is little
      midterm or long-term proof of their efficacy. METHODS: During the past 9 years,
      239 endovascular graft repairs were performed for nonruptured AAAs, many (86%) in
      high-risk patients or in those with complex anatomy. The grafts used were
      Montefiore (n = 97), Ancure/EVT (n = 14), Vanguard (n = 16), Talent (n = 47),
      Excluder (n = 20), AneuRx (n = 29), and Zenith (n = 16). All but the AneuRx and
      Ancure repairs were performed as part of a U.S. phase 1 or phase 2 clinical trial
      under a Food and Drug Administration investigational device exemption. Procedural
      outcomes and follow-up results were prospectively recorded. RESULTS: The major
      complication and death rates within 30 days of endovascular graft repair were
      17.6% and 8.5%, respectively. The technical success rate with complete AAA
      exclusion was 88.7%. During follow-up to 75 months (mean +/- standard deviation,
      15.7 +/- 6.3 months), 53 patients (22%) died of unrelated causes. Two AAAs
      treated with endovascular grafts ruptured and were surgically repaired, with one
      death. Other late complications included type 1 endoleak (n = 7), aortoduodenal
      fistula (n = 2), graft thrombosis/stenosis (n = 7), limb separation or fabric
      tear with a subsequent type 3 endoleak (n = 1), and a persistent type 2 endoleak
      (n = 13). Secondary intervention or surgery was required in 23 patients (10%).
      These included deployment of a second graft (n = 4), open AAA repair (n = 5),
      coil embolization (n = 6), extraanatomic bypass (n = 4), and stent placement (n =
      3). CONCLUSION: With longer follow-up, complications occurred with increasing
      frequency. Although most could be managed with some form of endovascular
      reintervention, some complications resulted in a high death rate. Although
      endovascular graft repair is less invasive and sometimes effective in the long
      term, it is often not a definitive procedure. These findings mandate long-term
      surveillance and prospective studies to prove the effectiveness of endovascular
      graft repair.

PMID- 11524586
TI  - New paradigms and improved results for the surgical treatment of acute type A
      dissection.
AB  - OBJECTIVE: To examine the effect of an integrated surgical approach to the
      treatment of acute type A dissections. SUMMARY BACKGROUND DATA: Acute type A
      dissection requires surgery to prevent death from proximal aortic rupture or
      malperfusion. Most series of the past decade have reported a death rate in the
      range of 15% to 30%. METHODS: From January 1994 to March 2001, 104 consecutive
      patients underwent repair of acute type A dissection. All had an integrated
      operative management as follows: intraoperative transesophageal echocardiography;
      hypothermic circulatory arrest (HCA) with retrograde cerebral perfusion (RCP) to
      replace the aortic arch; HCA established after 5 minutes of
      electroencephalographic (EEG) silence in neuromonitored patients (66%) or after
      45 minutes of cooling in patients who were not neuromonitored (34%);
      reinforcement of the residual arch tissue with a Teflon felt "neo-media";
      cannulation of the arch graft to reestablish cardiopulmonary bypass at the
      completion of HCA (antegrade graft perfusion); and remodeling of the sinus of
      Valsalva segments with Teflon felt "neo-media" and aortic valve resuspension
      (78%) or replacement with a biologic or mechanical valved conduit (22%). RESULTS:
      Mean age was 59 +/- 15 (range 22-86) years, with 71% men and 13% redo sternotomy
      after a previous cardiac procedure. Mean cardiopulmonary bypass time was 196 +/-
      50 minutes. Mean HCA with RCP time was 42 +/- 12 minutes (range 19-84). Mean
      cardiac ischemic time was 140 +/- 45 minutes. Eleven percent of patients
      presented with a preoperative neurologic deficit, and 5% developed a new
      cerebrovascular accident after dissection repair. The in-hospital death rate was
      9%. Excluding the patients who presented neurologically unresponsive or with
      ongoing cardiopulmonary resuscitation (n = 5), the death rate was 4%. In six
      patients adverse cerebral outcomes were potentially avoided when immediate
      surgical fenestration was prompted by a sudden change in the EEG during cooling.
      Forty-five percent of neuromonitored patients required greater than 30 minutes to
      achieve EEG silence. CONCLUSION: The authors have shown that the surgical
      integration of sinus segment repair or aortic root replacement, the use of EEG
      monitoring, partial or total arch replacement using RCP, routine antegrade graft
      perfusion, and the uniform use of transesophageal echocardiography substantially
      decrease the death and complication rates of acute type A dissection repair.

PMID- 11524587
TI  - Telomerase activity in periampullary tumors correlates with aggressive
      malignancy.
AB  - OBJECTIVE: To determine the presence of telomerase activity in a variety of
      periampullary malignancies and pancreatic diseases and quantify its activity to
      establish any association with the stage or aggressiveness of malignancy. SUMMARY
      BACKGROUND DATA: Progressive shortening of telomeres, repetitive DNA sequences at
      the ends of chromosomes, plays a role in cell senescence. Telomerase catalyzes
      conservation of telomeric repeats and may promote cell immortality and hence
      malignancy. It is absent in normal tissues but upregulated in more than 80% of
      cancers. METHODS: Fresh specimens of 62 periampullary tumors were snap-frozen in
      liquid nitrogen and adjacent tissue was formalin-fixed for histopathology. The
      telomerase repeat amplification protocol (TRAP) was used to obtain telomerase DNA
      products. These were separated with gel electrophoresis, stained with SYBR green,
      and quantified by densitometry. Findings were confirmed with a fluorometric TRAP
      assay in which fluorescent primers specific for telomerase were selectively
      amplified in its presence. RESULTS: Telomerase activity was upregulated in 26 of
      33 periampullary malignancies (79%): 17 of 21 pancreatic adenocarcinomas (81%), 2
      of 2 cholangiocarcinomas, 2 of 2 duodenal carcinomas, and 5 of 8 ampullary
      carcinomas (63%). Poorly differentiated periampullary tumors had significantly
      higher telomerase activity than well-differentiated tumors, and tumors larger
      than 2 cm had significantly higher telomerase activity than those 2 cm or
      smaller. Pancreatic ductal adenocarcinomas with lymph node metastases had
      significantly greater activity than node-negative cancers. Two of 11 intraductal
      papillary mucinous tumors were positive for telomerase activity, but only in foci
      of invasive carcinoma. Chronic pancreatitis (n = 7), serous cystadenomas (n = 5),
      benign mucinous cystic neoplasms (n = 4), neuroendocrine cancer (n = 1), and
      acinar cell carcinoma (n = 1) had no detectable telomerase activity. CONCLUSION:
      Telomerase activity is common in periampullary carcinomas. The magnitude of
      activity correlates with aggressiveness in pancreatic adenocarcinoma and may
      prove useful as a molecular index for biologic staging.

PMID- 11524589
TI  - Histologic tumor type is an independent prognostic parameter in esophageal
      cancer: lessons from more than 1,000 consecutive resections at a single center in
      the Western world.
AB  - OBJECTIVE: To analyze the changing pattern in tumor type and postoperative deaths
      at a national referral center for esophageal cancer in the Western world and to
      assess prognostic factors for long-term survival after resection. SUMMARY
      BACKGROUND DATA: During the past two decades, the epidemiology and treatment
      strategies of esophageal cancer have changed markedly in the Western world. The
      influence of these factors on postoperative deaths and long-term prognosis has
      not been adequately evaluated. METHODS: Between 1982 and 2000, 1,059 patients
      with primary esophageal squamous cell cancer or adenocarcinoma had resection with
      curative intention at a single center. Patient and tumor characteristics and
      details of the surgical procedure and outcome were documented during this period.
      Follow-up was available for 95.8% of the patients. Changing patterns in tumor
      type and postoperative deaths were analyzed. Prognostic factors for long-term
      survival were assessed by multivariate analysis. RESULTS: The prevalence of
      adenocarcinoma in patients with resected esophageal cancer increased markedly
      during the study period. The postoperative death rate decreased from about 10%
      before 1990 to less than 2% since 1994, coinciding with the introduction of a
      procedure-specific composite risk score and exclusion of high-risk patients from
      surgical resection. In addition to the well-established prognostic parameters,
      tumor cell type "adenocarcinoma" was identified as a favorable independent
      predictor of long-term survival after resection. The independent prognostic
      effect of tumor cell type persisted in the subgroups of patients with primary
      resection and patients with primary resection and R0 category. CONCLUSION:
      Esophagectomy for esophageal cancer has become a safe procedure in experienced
      hands. Esophageal adenocarcinoma has a better long-term prognosis after resection
      than squamous cell carcinoma.

PMID- 11524588
TI  - Local excision of T2 and T3 rectal cancers after downstaging chemoradiation.
AB  - OBJECTIVE: To evaluate the safety and efficacy of local excision in patients with
      T2 and T3 distal rectal cancers that have been downstaged by preoperative
      chemoradiation. SUMMARY BACKGROUND DATA: T2 and T3 cancers treated by local
      excision alone are associated with unacceptably high recurrence rates. The
      authors hypothesized that preoperative chemoradiation might downstage both T2 and
      T3 lesions and significantly expand the indications for local excision. METHODS:
      Local excision was performed after preoperative chemoradiation on patients with a
      complete clinical response or on patients who were either ineligible for or
      refused to undergo abdominoperineal resection. Local excision was approached
      transanally by removing full-thickness rectal wall and the underlying mesorectum.
      RESULTS: From 1994 to 2000, 95 patients with rectal cancers underwent
      preoperative chemoradiation and surgical resection for curative intent. Of these,
      26 patients (28%), 19 men and 7 women, with a mean age of 63 years (range 44-90),
      underwent local excision. Pretreatment endoscopic ultrasound classifications
      included 5 T2N0, 13 T3N0, 7 T3N1, and 1 not done. Pathologic partial and complete
      responses were achieved in 9 of 26 (35%) and 17 of 26 (65%) patients,
      respectively. Two of nine partial responders underwent immediate abdominoperineal
      resection. The mean follow-up was 24 months (median 19, range 6-77). The only
      recurrence was in a patient who refused to undergo abdominoperineal resection
      after a partial response. There was one postoperative death from a stroke. This
      treatment was associated with a low rate of complications. CONCLUSION: Local
      excision appears to be an effective alternative treatment to radical surgical
      resection for a highly select subset of patients with T2 and T3 adenocarcinomas
      of the distal rectum who show a complete pathologic response to preoperative
      chemoradiation.

PMID- 11524590
TI  - Comparison of surgical outcomes between teaching and nonteaching hospitals in the
      Department of Veterans Affairs.
AB  - OBJECTIVE: To determine whether the investment in postgraduate education and
      training places patients at risk for worse outcomes and higher costs than if
      medical and surgical care was delivered in nonteaching settings. SUMMARY
      BACKGROUND DATA: The Veterans Health Administration (VA) plays a major role in
      the training of medical students, residents, and fellows. METHODS: The database
      of the VA National Surgical Quality Improvement Program was analyzed for all
      major noncardiac operations performed during fiscal years 1997, 1998, and 1999.
      Teaching status of a hospital was determined on the basis of a background and
      structure questionnaire that was independently verified by a research fellow.
      Stepwise logistic regression was used to construct separate models predictive of
      30-day mortality and morbidity for each of seven surgical specialties and eight
      operations. Based on these models, a severity index for each patient was
      calculated. Hierarchical logistic regression models were then created to examine
      the relationship between teaching versus nonteaching hospitals and 30-day
      postoperative mortality and morbidity, after adjusting for patient severity.
      RESULTS: Teaching hospitals performed 81% of the total surgical workload and 90%
      of the major surgery workload. In most specialties in teaching hospitals, the
      residents were the primary surgeons in more than 90% of the operations. Compared
      with nonteaching hospitals, the patient populations in teaching hospitals had a
      higher prevalence of risk factors, underwent more complex operations, and had
      longer operation times. Risk-adjusted mortality rates were not different between
      the teaching and nonteaching hospitals in the specialties and operations studied.
      The unadjusted complication rate was higher in teaching hospitals in six of seven
      specialties and four of eight operations. Risk adjustment did not eliminate
      completely these differences, probably reflecting the relatively poor predictive
      validity of some of the risk adjustment models for morbidity. Length of stay
      after major operations was not consistently different between teaching and
      nonteaching hospitals. CONCLUSION: Compared with nonteaching hospitals, teaching
      hospitals in the VA perform the majority of complex and high-risk major
      procedures, with comparable risk-adjusted 30-day mortality rates. Risk-adjusted
      30-day morbidity rates in teaching hospitals are higher in some specialties and
      operations than in nonteaching hospitals. Although this may reflect the weak
      predictive validity of some of the risk adjustment models for morbidity, it may
      also represent suboptimal processes and structures of care that are unique to
      teaching hospitals. Despite good quality of care in teaching hospitals, as
      evidenced by the 30-day mortality data, efforts should be made to examine further
      the structures and processes of surgical care prevailing in these hospitals.

PMID- 11524591
TI  - A 10-year experience of liver transplantation for hepatitis C: analysis of
      factors determining outcome in over 500 patients.
AB  - OBJECTIVE: To determine the factors affecting the outcome of orthotopic liver
      transplantation (OLT) for end-stage liver disease caused by hepatitis C virus
      (HCV) and to identify models that predict patient and graft survival. SUMMARY
      BACKGROUND DATA: The national epidemic of HCV infection has become the leading
      cause of hepatic failure that requires OLT. Rapidly increasing demands for OLT
      and depleted donor organ pools mandate appropriate selection of patients and
      donors. Such selection should be guided by a better understanding of the factors
      that influence the outcome of OLT. METHODS: The authors conducted a retrospective
      review of 510 patients who underwent OLT for HCV during the past decade. Seven
      donor, 10 recipient, and 2 operative variables that may affect outcome were
      dichotomized at the median for univariate screening. Factors that achieved a
      probability value less than 0.2 or that were thought to be relevant were entered
      into a stepdown Cox proportional hazard regression model. RESULTS: Overall
      patient and graft survival rates at 1, 5, and 10 years were 84%, 68%, and 60% and
      73%, 56%, and 49%, respectively. Overall median time to HCV recurrence was 34
      months after transplantation. Neither HCV recurrence nor HCV-positive donor
      status significantly decreased patient and graft survival rates by Kaplan-Meier
      analysis. However, use of HCV-positive donors reduced the median time of
      recurrence to 22.9 months compared with 35.7 months after transplantation of HCV
      negative livers. Stratification of patients into five subgroups, based on time of
      recurrence, revealed that early HCV recurrence was associated with significantly
      increased rates of patient death and graft loss. Donor, recipient, and operative
      variables that may affect OLT outcome were analyzed. On univariate analysis,
      recipient age, serum creatinine, donor length of hospital stay, donor female
      gender, United Network for Organ Sharing (UNOS) status of recipient, and presence
      of hepatocellular cancer affected the outcome of OLT. Elevation of pretransplant
      HCV RNA was associated with an increased risk of graft loss. Of 15 variables
      considered by multivariate Cox regression analysis, recipient age, UNOS status,
      donor gender, and log creatinine were simultaneous significant predictors for
      patient survival. Simultaneously significant factors for graft failure included
      log creatinine, log alanine transaminase, log aspartate transaminase, UNOS
      status, donor gender, and warm ischemia time. These variables were therefore
      entered into prognostic models for patient and graft survival. CONCLUSION: The
      earlier the recurrence of HCV, the greater the impact on patient and graft
      survival. The use of HCV-positive donors may accelerate HCV recurrence, and they
      should be used judiciously. Patient survival at the time of transplantation is
      predicted by donor gender, UNOS status, serum creatinine, and recipient age.
      Graft survival is affected by donor gender, warm ischemia time, and pretransplant
      patient condition. The authors' current survival prognostic models require
      further multicenter validation.

PMID- 11524592
TI  - Selective nonoperative management in 1,856 patients with abdominal gunshot
      wounds: should routine laparotomy still be the standard of care?
AB  - OBJECTIVE: To evaluate the safety of a policy of selective nonoperative
      management (SNOM) in patients with abdominal gunshot wounds. SUMMARY BACKGROUND
      DATA: Selective nonoperative management is practiced extensively in stab wounds
      and blunt abdominal trauma, but routine laparotomy is still the standard of care
      in abdominal gunshot wounds. METHODS: The authors reviewed the medical records of
      1,856 patients with abdominal gunshot wounds (1,405 anterior, 451 posterior)
      admitted during an 8-year period in a busy academic level 1 trauma center and
      managed by SNOM. According to this policy, patients who did not have peritonitis,
      were hemodynamically stable, and had a reliable clinical examination were
      observed. RESULTS: Initially, 792 (42%) patients (34% of patients with anterior
      and 68% with posterior abdominal gunshot wounds) were selected for nonoperative
      management. During observation 80 (4%) patients developed symptoms and required a
      delayed laparotomy, which revealed organ injuries requiring repair in 57. Five
      (0.3%) patients suffered complications potentially related to the delay in
      laparotomy, which were managed successfully. Seven hundred twelve (38%) patients
      were successfully managed without an operation. The rate of unnecessary
      laparotomy was 14% among operated patients (or 9% among all patients). If
      patients were managed by routine laparotomy, the unnecessary laparotomy rate
      would have been 47% (39% for anterior and 74% for posterior abdominal gunshot
      wounds). Compared with patients with unnecessary laparotomy, patients managed
      without surgery had significantly shorter hospital stays and lower hospital
      charges. By maintaining a policy of SNOM instead of routine laparotomy, a total
      of 3,560 hospital days and $9,555,752 in hospital charges were saved over the
      period of the study. CONCLUSION: Selective nonoperative management is a safe
      method for managing patients with abdominal gunshot wounds in a level 1 trauma
      center with an in-house trauma team. It reduces significantly the rate of
      unnecessary laparotomy and hospital charges.

PMID- 11524594
TI  - Role of plasmapheresis in the management of acute hepatic failure in children.
AB  - OBJECTIVE: To assess the efficacy of plasmapheresis in the treatment of children
      with acute hepatic failure. SUMMARY BACKGROUND DATA: Acute liver failure is
      expressed with severe encephalopathy, coagulopathy, and subsequent multisystem
      organ failure, resulting in a high death rate. Liver transplantation is
      considered the best option, with long-term 1-year survival rates exceeding 88%.
      It has been suggested that plasmapheresis may improve coagulopathy and prevent
      bleeding complications while maintaining adequate fluid, electrolyte, and acid
      base balance. METHODS: Forty-nine patients with acute liver failure underwent a
      total of 243 therapeutic plasma exchanges (TPE). Indications for treatment
      included candidacy for liver transplant and prolonged prothrombin time. Pheresis
      was performed daily until the patient recovered, died, or was transplanted. Four
      patients were anhepatic during pheresis. RESULTS: Coagulation profiles after TPE
      significantly improved compared with mean preexchange values while maintaining
      euvolemia. No bleeding episodes were observed during the course of treatment.
      There was no sustained improvement in neurologic function. Spontaneous recovery
      was observed in three patients; the remaining either underwent transplantation
      (32/49) or were not considered transplant candidates because of irreversible
      neurologic insults (11/49) or sepsis (3/49). CONCLUSION: For children with acute
      liver failure, TPE is extremely effective in preventing life-threatening bleeding
      while maintaining appropriate volume status in small children. This method of
      treatment has no effect on the neurologic complications of liver failure and has
      no impact on the ability of the liver to regenerate.

PMID- 11524595
TI  - Letter of apologia. Duplicate publication.

PMID- 11524593
TI  - Clinical intestinal transplantation: a decade of experience at a single center.
AB  - OBJECTIVE: To assess the long-term efficacy of intestinal transplantation under
      tacrolimus-based immunosuppression and the therapeutic benefit of newly developed
      adjunct immunosuppressants and management strategies. SUMMARY BACKGROUND DATA:
      With the advent of tacrolimus in 1990, transplantation of the intestine began to
      emerge as therapy for intestinal failure. However, a high risk of rejection, with
      the consequent need for acute and chronic high-dose immunosuppression, has
      inhibited its widespread application. METHODS: During an 11-year period, divided
      into two segments by a 1-year moratorium in 1994, 155 patients received 165
      intestinal allografts under immunosuppression based on tacrolimus and prednisone:
      65 intestine alone, 75 liver and intestine, and 25 multivisceral. For the
      transplantations since the moratorium (n = 99), an adjunct immunosuppressant
      (cyclophosphamide or daclizumab) was used for 74 transplantations, adjunct donor
      bone marrow was given in 39, and the intestine of 11 allografts was irradiated
      with a single dose of 750 cGy. RESULTS: The actuarial survival rate for the total
      population was 75% at 1 year, 54% at 5 years, and 42% at 10 years. Recipients of
      liver plus intestine had the best long-term prognosis and the lowest risk of
      graft loss from rejection (P =.001). Since 1994, survival rates have improved.
      Techniques for early detection of Epstein-Barr and cytomegaloviral infections,
      bone marrow augmentation, the adjunct use of the interleukin-2 antagonist
      daclizumab, and most recently allograft irradiation may have contributed to the
      better results. CONCLUSION: The survival rates after intestinal transplantation
      have cumulatively improved during the past decade. With the management strategies
      currently under evaluation, intestinal transplant procedures have the potential
      to become the standard of care for patients with end-stage intestinal failure.

PMID- 11524597
TI  - Bioethics: using its historical and social context.

PMID- 11524598
TI  - Phase I cancer trials: a crucible of competing priorities.

PMID- 11524599
TI  - End-of-life issues and the anesthesiologist.

PMID- 11524600
TI  - Do-not-resuscitate orders: from the ward to the operating room; from procedures
      to goals.

PMID- 11524601
TI  - Cardiopulmonary resuscitation: medical decision or patient/surrogate choice?

PMID- 11524602
TI  - Practical guidelines on the withdrawal of life-sustaining therapies.

PMID- 11524603
TI  - Non-heartbeating organ donation: ethical controversies and medical
      considerations.

PMID- 11524604
TI  - Report of panel on cost containment, informed consent, and outcome
      accountability: an ethical dilemma.

PMID- 11524605
TI  - The ethical boundaries of persuasion: coercion and restraint of patients in
      clinical anesthesia practice.

PMID- 11524608
TI  - Metabotropic glutamate receptor subtypes as targets for neuroprotective drugs.
AB  - Metabotropic glutamate (mGlu) receptors have been considered as potential targets
      for neuroprotective drugs, but the lack of specific drugs has limited the
      development of neuroprotective strategies in experimental models of acute or
      chronic central nervous system (CNS) disorders. The advent of potent and
      centrally available subtype-selective ligands has overcome this limitation,
      leading to an extensive investigation of the role of mGlu receptor subtypes in
      neurodegeneration during the last 2 years. Examples of these drugs are the
      noncompetitive mGlu1 receptor antagonists, CPCCOEt and BAY-36-7620; the
      noncompetitive mGlu5 receptor antagonists, 2-methyl-6-(phenylethynyl)pyridine,
      SIB-1893, and SIB-1757; and the potent mGlu2/3 receptor agonists, LY354740 and
      LY379268. Pharmacologic blockade of mGlu1 or mGlu5 receptors or pharmacologic
      activation of mGlu2/3 or mGlu4/7/8 receptors produces neuroprotection in a
      variety of in vitro or in vivo models. MGlu1 receptor antagonists are promising
      drugs for the treatment of brain ischemia or for the prophylaxis of neuronal
      damage induced by synaptic hyperactivity. MGlu5 receptor antagonists may limit
      neuronal damage induced by a hyperactivity of N-methyl-d-aspartate (NMDA)
      receptors, because mGlu5 and NMDA receptors are physically and functionally
      connected in neuronal membranes. A series of observations suggest a potential
      application of mGlu5 receptor antagonists in chronic neurodegenerative disorders,
      such as amyotrophic lateral sclerosis and Alzheimer disease. MGlu2/3 receptor
      agonists inhibit glutamate release, but also promote the synthesis and release of
      neurotrophic factors in astrocytes. These drugs may therefore have a broad
      application as neuroprotective agents in a variety of CNS disorders. Finally,
      mGlu4/7/8 receptor agonists potently inhibit glutamate release and have a
      potential application in seizure disorders. The advantage of all these drugs with
      respect to NMDA or AMPA receptor agonists derives from the evidence that mGlu
      receptors do not "mediate," but rather "modulate" excitatory synaptic
      transmission. Therefore, it can be expected that mGlu receptor ligands are devoid
      of the undesirable effects resulting from the inhibition of excitatory synaptic
      transmission, such as sedation or an impairment of learning and memory.

PMID- 11524609
TI  - Imaging human mesolimbic dopamine transmission with positron emission tomography:
      I. Accuracy and precision of D(2) receptor parameter measurements in ventral
      striatum.
AB  - Dopamine transmission in the ventral striatum (VST), a structure which includes
      the nucleus accumbens, ventral caudate, and ventral putamen, plays a critical
      role in the pathophysiology of psychotic states and in the reinforcing effects of
      virtually all drugs of abuse. The aim of this study was to assess the accuracy
      and precision of measurements of D(2) receptor availability in the VST obtained
      with positron emission tomography on the high-resolution ECAT EXACT HR+ scanner
      (Siemens Medical Systems, Knoxville, TN, U.S.A.). A method was developed for
      identification of the boundaries of the VST on coregistered high-resolution
      magnetic resonance imaging scans. Specific-to-nonspecific partition coefficient
      (V(3)") and binding potential (BP) of [(11)C]raclopride were measured twice in 10
      subjects, using the bolus plus constant infusion method. [(11)C]Raclopride V(3)"
      in the VST (1.86 +/- 0.29) was significantly lower than in the dorsal caudate
      (DCA, 2.33 +/- 0.28) and dorsal putamen (DPU, 2.99 +/- 0.26), an observation
      consistent with postmortem studies. The reproducibility of V(3)" and BP were
      appropriate and similar in VST (V(3)" test-retest variability of 8.2% +/- 6.2%,
      intraclass correlation coefficient = 0.83), DCA (7.7% +/- 5.1%, 0.77), DPU (6.0%
      +/- 4.1%, 0.71), and striatum as a whole (6.3% +/- 4.1%, 0.78). Partial volume
      effects analysis revealed that activities in the VST were significantly
      contaminated by counts spilling over from the adjacent DCA and DPU: 70% +/- 5% of
      the specific binding measured in the VST originated from D(2) receptors located
      in the VST, whereas 12% +/- 3% and 18% +/- 3% were contributed by D(2) receptors
      in the DCA and DPU, respectively. Thus, accuracy of D(2) receptor measurement is
      improved by correction for partial voluming effects. The demonstration of an
      appropriate accuracy and precision of D(2) receptor measurement with
      [(11)C]raclopride in the VST is the first critical step toward the use of this
      ligand in the study of synaptic dopamine transmission at D(2) receptors in the
      VST using endogenous competition techniques.

PMID- 11524610
TI  - Postural effects on brain hemodynamics in unilateral cerebral artery occlusive
      disease: a positron emission tomography study.
AB  - To investigate effect of assuming of upright posture on brain hemodynamics in
      patients with unilateral internal carotid or middle cerebral artery occlusion
      (MCAO), local tissue oxygen extraction fraction (OEF), and postural changes in
      regional cerebral blood flow (rCBF) during supine and sitting conditions were
      examined using positron emission tomography (PET) with (15)O-gas steady-state
      method and H(2)(15)O autoradiographic method. A total of 22 minor stroke patients
      at relatively early stages participated. The regions of interest method was used
      for analyzing levels of perfusion and oxygen metabolic parameters, and postural
      rCBF change within MCAO group was investigated using statistical parametric
      mapping. Region of interest analyses showed significant rCBF reduction in the
      cortical and subcortical regions distal to the artery occlusion in CAO patients
      during sitting. Regression analyses showed that magnitudes of rCBF reduction in
      those areas were correlated positively with OEF values and inversely with
      metabolic rates of oxygen (P < 0.05). Statistical parametric mapping for MCAO
      patients demonstrated further rCBF reduction by sitting in the occlusion-side MCA
      territory. The current study suggested that assumption of upright posture could
      exert an adverse effect on local perfusion in hemodynamically compromised
      patients with major cerebral vessel occlusion, possibly caused by impairment of
      local autoregulation.

PMID- 11524611
TI  - Relation of cerebral energy metabolism and extracellular nitrite and nitrate
      concentrations in patients after aneurysmal subarachnoid hemorrhage.
AB  - In a prospective clinical investigation on neurochemical intensive care
      monitoring, the authors' aim was to elucidate the temporal profile of nitric
      oxide metabolite concentrations-that is, nitrite and nitrate (NO(x))--and
      compounds related to energy-metabolism in the cerebral interstitium of patients
      after aneurysmal subarachnoid hemorrhage (SAH). During aneurysm surgery,
      microdialysis probes were implanted in cerebral white matter of the vascular
      territory most likely affected by vasospasm. Temporal profiles of NO(x) were
      analyzed in a subset of 10 patients (7 female, 3 male, mean age = 47 +/- 14
      years). Microdialysis was performed for 152 +/- 63 hours. Extracellular
      metabolites (glucose, lactate, pyruvate, glutamate) were recovered from the
      extracellular fluid of the cerebral parenchyma. NO(x) was measured using a
      fluorometric assay. After early surgery, SAH patients revealed characteristic
      decreases of NO(x) from initial values of 46.2 +/- 34.8 micromol/L to 23.5 +/-
      9.0 micromol/L on day 7 after SAH (P < 0.05). Decreases in NO(x) were seen
      regardless of development of delayed ischemia (DIND). Overall NO(x) correlated
      intraindividually with glucose, lactate, and glutamate (r = 0.58, P < 0.05; r =
      0.32, P < 0.05; r = 0.28, P < 0.05; respectively). After SAH, cerebral
      extracellular concentrations of NO metabolites decrease over time and are
      associated with concomitant alterations in energy-or damage-related compounds.
      This could be related to reduced NO availability, potentially leading to an
      imbalance of vasodilatory and vasoconstrictive factors. On the basis of the
      current findings, however, subsequent development of DIND cannot be explained by
      a lack of vasodilatory NO alone.

PMID- 11524612
TI  - Glutamate, NMDA, and AMPA induced changes in extracellular space volume and
      tortuosity in the rat spinal cord.
AB  - Glutamate release, particularly in pathologic conditions, may result in cellular
      swelling. The authors studied the effects of glutamate, N-methyl-D-aspartate
      (NMDA), and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) on
      extracellular pH (pH(e)), extracellular potassium concentration ([K(+)](e)), and
      changes in extracellular space (ECS) diffusion parameters (volume fraction alpha,
      tortuosity lambda) resulting from cellular swelling. In the isolated spinal cord
      of 4-to 12-day-old rats, the application of glutamate receptor agonists induced
      an increase in [K(+)](e), alkaline-acid shifts, a substantial decrease in alpha,
      and an increase in lambda. After washout of the glutamate receptor agonists,
      alpha either returned to or overshot normal values, whereas lambda remained
      elevated. Pretreatment with 20 mmol/L Mg(++), MK801, or CNQX blocked the changes
      in diffusion parameters, [K(+)](e) and pH(e) evoked by NMDA or AMPA. However, the
      changes in diffusion parameters also were blocked in Ca(2+)-free solution, which
      had no effect on the [K(+)](e) increase or acid shift. The authors conclude that
      increased glutamate release may produce a large, sustained and [Ca(2+)](e)
      dependent decrease in alpha and increase in lambda. Repetitive stimulation and
      pathologic states resulting in glutamate release therefore may lead to changes in
      ECS volume and tortuosity, affecting volume transmission and enhancing glutamate
      neurotoxicity and neuronal damage.

PMID- 11524613
TI  - Proteolysis of oxidized proteins after oxygen-glucose deprivation in rat cortical
      neurons is mediated by the proteasome.
AB  - Oxidative injury contributes to cellular damage during and after cerebral
      ischemia. However, the downstream catabolic pathways of damaged cellular
      components in neurons are largely unknown. In the current study, the authors
      examined the formation of oxidized proteins and their active degradation by the
      proteasome. In near-pure rat primary cortical neurons, it was found that protein
      bound carbonyls as markers for oxidized proteins are increased after oxygen
      glucose deprivation (OGD). During and after OGD, degradation of proteins
      metabolically radiolabeled before OGD increases two-to threefold compared with
      the normal protein turnover. Proteolysis after reoxygenation was attenuated by
      the presence of dimethylthiourea, a radical scavenger, and was blocked by
      lactacystin, a specific proteasome inhibitor. Lactacystin also increased the
      amount of protein carbonyls formed. In contrast, the activity of the proteasome
      complex itself after OGD was not different from sham-washed controls. The authors
      suggest that oxygen-glucose deprivation increases free radicals, which, in turn,
      oxidize proteins that are recognized and actively degraded by the proteasome
      complex. This protease itself is relatively resistant against oxidative injury.
      The authors conclude that the proteasome may be an active part of the cellular
      defense system against oxidative stress after cerebral ischemia.

PMID- 11524614
TI  - Administration of transforming growth factor-alpha reduces infarct volume after
      transient focal cerebral ischemia in the rat.
AB  - Growth factors promote cell growth and survival and protect the brain from
      developing injury after ischemia. In this article, the authors examined whether
      transforming growth factor-alpha (TGF-alpha) was protective in transient focal
      ischemia and whether alteration of cerebral circulation was involved. Rats
      received intraventricular TGF-alpha (50 ng, either split into 2 doses given 30
      minutes before and 30 minutes after middle cerebral artery occlusion (MCAO), or 1
      dose given 30 minutes after MCAO) or vehicle. Rats were subjected to 1-hour
      intraluminal MCAO and cerebral blood flow was recorded continuously by laser
      Doppler flowmetry. Infarct volume was measured 1 and 4 days later. The effects of
      TGF-alpha on arterial tone were assessed in isolated rabbit basilar and common
      carotid arteries. Transforming growth factor-alpha before and after ischemia
      reduced infarct volume by 70% at 1 day and 50% at 4 days. Transforming growth
      factor-alpha given only after ischemia also did reduce infarct volume by 70% at 1
      day and 80% at 4 days. The protective effect was more marked in cortex than in
      striatum. Transforming growth factor-alpha did not change cortical microvascular
      perfusion and did not modify arterial passive tone nor agonist-induced active
      tone. It can be concluded that TGF-alpha reduces infarct volume, even when the
      factor is exclusively administered at reperfusion, and that this effect is not
      mediated by changes in microvascular perfusion or cerebral arteries. It is
      therefore suggested that TGF-alpha has a protective effect against neuronal cell
      death after transient focal ischemia.

PMID- 11524615
TI  - Hypoxic preconditioning induces changes in HIF-1 target genes in neonatal rat
      brain.
AB  - Hypoxic preconditioning induces tolerance to hypoxic-ischemic injury in neonatal
      rat brain and is associated with changes in gene expression. Hypoxia-inducible
      factor-1 (HIF-1) is a transcription factor that is strongly induced by hypoxia or
      the hypoxia-mimetic compound cobalt chloride (CoCl(2)). Hypoxia-inducible factor
      1 modulates the expression of several target genes including the glycolytic
      enzymes, glucose transporter-1 (GLUT-1), and erythropoietin. Recently, HIF-1
      expression was shown to increase after hypoxic and CoCl(2) preconditioning in
      newborn rat brain. To study the involvement of HIF-1 target genes in neonatal
      hypoxia-induced ischemic tolerance, the authors examined the brains of newborn
      rats after exposure to hypoxia (8% O(2) for 3 hours) or injection of CoCl(2) (60
      mg/kg). Preconditioning with hypoxia or CoCl(2) 24 hours before hypoxia-ischemia
      afforded a 96% and 76% brain protection, respectively, compared with littermate
      control animals. Hypoxic preconditioning increased the expression of GLUT-1 mRNA
      and protein, and of aldolase, phosphofructokinase, and lactate dehydrogenase
      proteins but not mRNA. This suggests that the modulation of glucose transport and
      glycolysis by hypoxia may contribute to the development of hypoxia-induced
      tolerance. In contrast, preconditioning with CoCl(2) did not produce any change
      in HIF-1 target gene expression suggesting that different molecular mechanisms
      may be involved in the induction of tolerance by hypoxia and CoCl(2) in newborn
      brain.

PMID- 11524616
TI  - Recruitment of neutrophils across the blood-brain barrier: the role of E- and P
      selectins.
AB  - The adult central nervous system parenchyma is resistant to inflammation, but in
      juvenile rats the injection of inflammatory mediators, interleukin-1 beta for
      example, gives rise to extensive neutrophil recruitment and neutrophil-dependent
      blood-brain barrier breakdown. The factors that confer this resistant phenotype
      are unknown. In this study, the authors demonstrate that E- and P-selectin
      expression is increased to a similar extent in adult and juvenile brain after the
      intracerebral injection of IL-1 beta. Thus, the refractory nature of the brain
      parenchyma cannot be attributed to an absence of selectin expression. However, in
      injuries where the resistant characteristic of the brain parenchyma is
      compromised, and neutrophil recruitment occurs, selectin blockade may be an
      advantage. The authors investigated the contribution that selectins make to
      neutrophil recruitment during acute inflammation in the brain. The authors
      examined neutrophil recruitment by immunohistochemistry on brain sections of
      juvenile rats killed four hours after the intracerebral injection of IL-1 beta
      and the intravenous injection of neutralizing anti-selectin monoclonal antibodies
      (mAb). The administration of the P-selectin blocking mAb inhibited neutrophil
      recruitment by 85% compared with controls. Surprisingly, E-selectin blockade had
      no effect on neutrophil recruitment to the brain parenchyma. Thus, P-selectin
      appears to play a pivotal role in mediating neutrophil recruitment to the brain
      parenchyma during acute inflammation.

PMID- 11524617
TI  - Cationic polymer and lipids augment adenovirus-mediated gene transfer to cerebral
      arteries in vivo.
AB  - Adenovirus-mediated gene transfer to blood vessels is relatively inefficient
      because binding of adenovirus to vessels is limited. The authors have reported
      that incorporation of cationic polymer and lipids with adenovirus augments gene
      transfer to blood vessels ex vivo. In this study, the authors determined whether
      complexes of adenovirus and cations improve efficiency of gene transfer in vivo.
      Poly-L-lysine, lipofectamine, or lipofectin was complexed with adenovirus
      encoding beta-galactosidase. Optimum ratios of the cations per adenovirus were
      determined by gene transfer to fibroblasts. After injection of the adenovirus
      into the cisterna magna of anesthetized rabbits, transgene activity was greater
      in the adventitia of intracranial arteries and meninges after injection of the
      complexes than adenovirus alone. Thirty minutes after application of adenovirus
      with the cations, binding of adenovirus to fibroblast cells in vitro or the
      basilar artery in vivo (by Southern blot analysis) was augmented, which suggests
      that enhanced binding of virus contributes to augmentation of transgene
      expression. Thus, cationic polymer and lipids improve transgene expression in
      intracranial arteries, primarily in the adventitia, after adenovirus-mediated
      gene transfer in vivo. This strategy may be applicable to studies of gene
      transfer and eventually for gene therapy.

PMID- 11524618
TI  - Chorangiosis and its precursors: underdiagnosed placental indicators of chronic
      fetal hypoxia.

PMID- 11524621
TI  - Osteogenesis imperfecta in pregnancy: two case reports and review of literature.
AB  - Osteogenesis imperfecta (OI) is an inherited disease where basic pathology is of
      defective maturation of collagen. It is more common in women, and the incidence
      in pregnancy is 1 in 25,000 to 30,000. A multidisciplinary approach is necessary.
      Ideally, genetic counseling is sought before conception. Once pregnant, prenatal
      diagnosis can be established by chorion villous sampling. Serial scans would
      identify the affected fetus with fractures. A cesarean delivery is advocated if
      the fetus is affected or if the mother has pelvic fractures. An experienced
      anesthetist should be involved. Because these women are more likely to have a
      postpartum hemorrhage due to uterine atony, Syntocinon infusion and close
      observation in the third stage is indicated.

PMID- 11524622
TI  - Cervical adenocarcinoma in situ: a systematic review of therapeutic options and
      predictors of persistent or recurrent disease.
AB  - The incidence of cervical adenocarcinoma in situ is increasing in frequency, and
      our limited knowledge about this lesion presents the physician with a therapeutic
      dilemma. Treatment for this lesion has included conservative therapy, large loop
      excision or cold-knife cone biopsy, or definitive therapy consisting of
      hysterectomy. But, rates of residual adenocarcinoma in situ after cone biopsy
      with negative margins vary from 0% to 40%, and residual disease rates as high as
      80% have been noted when the margins are positive. Despite these recent data on
      follow-up after conservative therapy such as cone biopsy, it seems that this
      method is safe and gaining acceptance by many physicians and patients. However,
      the short follow-up duration and small number of patients limit the conclusions
      of many studies. The relative infrequency of this diagnosis has precluded
      extensive clinical experience with the natural history of this lesion.

PMID- 11524623
TI  - Use of third generation gonadotropin-releasing hormone antagonists in in vitro
      fertilization-embryo transfer: a review.
AB  - Before gonadotropin-releasing hormone agonists (GnRHa) became available,
      approximately 20% of stimulated cycles within an in vitro fertilization (IVF)
      program were cancelled due to premature LH surges. By using the GnRHa to prevent
      LH surges via gonadotrope GnRH receptor down-regulation and desensitization, this
      percentage decreased to about 2%, and concomitantly, the IVF and pregnancy rates
      per cycle initiated were increased. Several treatment schedules currently are in
      use, including the so-called "long protocol," in which the GnRHa is begun in the
      luteal phase and down-regulation occurs before the start of the gonadotropin
      stimulation treatment phase. This is generally the most effective regimen and is
      presently the most frequently used protocol. However, it has some disadvantages,
      such as hypoestrogenic side effects and an increase in the number of ampules of
      FSH or hMG required for adequate stimulation. There is a new generation of GnRH
      antagonists now clinically available, that has been able to minimize the
      potential side effects and provide reliable antagonism at the GnRH receptor.
      These agents seem better suited than GnRHa for assisted reproductive technology
      (ART) cycles inasmuch as they can prevent LH surges without requiring complete
      gonadotropin suppression. We have reviewed the current literature concerning
      their use in IVF cycles.

PMID- 11524626
TI  - Trans-disciplinarity.

PMID- 11524627
TI  - Time, love and species.
AB  - Physiological and behavioral phenomena of many animals are restricted to certain
      times of the day. Many organisms show daily rhythms in their mating. The daily
      fluctuation in mating activity of a few insects is controlled by an endogenous
      clock. The fruitfly, Drosophila, is the most suitable material to characterize
      the genetic basis of circadian rhythms of mating because some mutants with
      defective core oscillator mechanism, feedback loops, have been isolated. D.
      melanogaster wild-type display a robust circadian rhythm in the mating activity,
      and the rhythms are abolished in period or timeless null mutant flies (per(01)
      and tim(01)), the rhythms are generated by females but not males. Disconnected
      (disco) mutants which have a severe defect in the optic lobe and are missing
      lateral neurons show arrhythmicity in mating activities. Thus, the lateral
      neurons seem to be essential for the circadian rhythm in mating activity of
      Drosophila. Furthermore, an anti-phasic relation in circadian rhythms of the
      mating activity was detected between D. melanogaster and their sibling species D.
      simulans. The Queensland fruit flies or wild gypsy moth also show species
      specific mating rhythm, suggesting that species-specific circadian rhythms in
      mating activity of insect appear to cause a reproductive isolation.

PMID- 11524628
TI  - Disturbances of diurnal rhythms of biogenic amines contents in hypothalamic
      nuclei as an evidence of neurotropic effects of enterotropic carcinogen 1,2
      dimethylhydrazine.
AB  - OBJECTIVES: Our data on the contents of norepinephrine (NE), dopamine (DA) and
      the metabolite of serotonin 5-hydroxyindoleacetic acid (5-HIAA) measured in the
      suprachiasmatic nuclei (SCN), preoptic area (PA) and median eminence (ME) of
      hypothalamus of rats after single subcutaneous injection of 1,2-dimethylhydrazine
      (DMH) as well as the effect of this carcinogen on formation of reactive oxygen
      species (ROS) in the PA are presented in this paper. RESULTS: Diurnal changes of
      DA in all studied brain structures and of NE in the PA have been observed in the
      control group. Their morning levels were higher than evening ones. Rhythms of 5
      HIAA in the SCN and diurnal changes of ROS formation have been shown to have
      contrary changes in control. Both the morning (11 a.m.) and evening (11 p.m.)
      subcutaneous administration of DMH at the dose of 21 mg/kg of body weight
      resulted in changes of all rhythms observed in control. In some cases a phase
      shift was found, in others the rhythms of neurotransmitters and ROS formation
      disappeared entirely. CONCLUSION: The data obtained confirm the idea of
      dopaminergic and serotoninergic systems taking part in mechanisms of a response
      of the hypothalamic nuclei to non-photic stimuli. It is suggested that the effect
      of DMH on the content and diurnal rhythms of neurotransmitters in the
      hypothalamic structures under study is due to its affecting activities of the
      enzymes of biogenic amines synthesis, synaptic transmission, melatonin synthesis
      and secretion rhythms. The change in ROS formation that is caused by
      administration of DMH is likely to be due to a disturbance of diurnal rhythms of
      neurotransmitters that are one of the sources of formation of free radicals in
      the brain.

PMID- 11524629
TI  - The insulin, glucose and cholesterol level and activity of lysosomal enzymes in
      the course of the model alloxan diabetes.
AB  - OBJECTIVES: The study was carried out on fifty male rabbits of the New Zealand
      White breed. Diabetes was caused by a single, intravenous alloxan injection.
      Rabbits which had glycaemia 7th day after the alloxan administration higher than
      11 millimol/litre were selected for the studies. They were divided into 5 groups:
      I - control (without diabetes); II - 3-week diabetes; III - 6-week diabetes; IV -
      3-month diabetes; V - 6-month diabetes. METHODS: In control and experimental
      rabbits the activity of beta-glucuronidase, N-acetyl-beta-glucosaminidase,
      lysosomal acid phosphatase, leucine aminopeptidase, cathepsin D, and lysosomal
      arylesterase was determined in lysosomal fractions of the liver and kidney.
      RESULTS: Alloxan caused lowering of the activity of all the investigated enzymes
      in the kidney and liver except lysosomal arylesterase. CONCLUSION: Alloxan
      injection caused a significant increase in the activity of all the investigated
      enzymes. The advisable lysosomal enzymes may be useful for the monitoring of the
      course and effectiveness of diabetes therapy.

PMID- 11524630
TI  - Effects of tandospirone, a serotonin-1A agonist, on the hypothalamo-pituitary
      gonadal axis of male patients.
AB  - BACKGROUND: Serotonin (5-HT) agonists are reported to affect prolactin (PRL) and
      gonadotropin secretion. A small study was conducted on male patients with
      generalized anxiety disorders to investigate the clinical and
      neuroendocrinological effects of the 5-HT(1A) receptor agonist tandospirone (TDS)
      on the hypothalamo-pituitary-gonadal (HPG) axis. METHODS: The subjects for the
      present study included 11 male outpatients. Informed consent was obtained from
      all subjects involved in this study. The endocrine studies were done before and
      during TDS administration. Psychiatric ratings were done using the Japanese
      version of the Spielberger's State-Trait Anxiety Inventory. RESULTS: We found
      that both state- and trait-anxiety scores were significantly reduced by TDS
      treatment; there was no significant difference in PRL, gonadotropins or
      testosterone (T) between the patients and normal controls; TDS administration
      showed significant stimulatory effects on PRL and T; and PRL change between
      baseline and TDS steady state (DeltaPRL) did not show a significant correlation
      with improvement in state or trait-anxiety scores. CONCLUSIONS: Our results
      indicate that PRL response may not provide a clinical predictor; (2) PRL level
      may not reflect the level of anxiety, and 5-HT(1A) may have stimulatory effects
      on PRL. However, further, double-blind evaluation with a larger sample would be
      needed for clarification of effects of 5-HT(1A) on the HPG axis.

PMID- 11524631
TI  - High incidence of hyperandrogenism-related clinical signs in patients with
      multiple sclerosis.
AB  - A mild prevalence of multiple sclerosis (MS) is present in females (2:1). To
      elucidate the pathogenetic role of sex steroids on the disease, we studied 76
      women affected by MS, compared to 50 healthy women (mean age +/- SD, 34.9 +/- 0.9
      vs. 33.4 +/- 1.7 years). The menarche was at mean age of 12.3 +/- 0.2 vs. 12.4 +/
      0.2. Interval between menses was 28.0 +/- 0.3 vs 27.8 +/- 0.3 days, with
      duration of menstrual flow of 5.0 +/- 0.2 vs. 5.0 +/- 0.2 days. Oligo- or
      amenorrhea was present in 20% of patients and in 16% of controls. Oral
      contraceptives were assumed by 21% of patients and 34% of controls (n.s.).
      Premenstrual symptoms were found in 43% of patients and in 46% of controls
      (n.s.). The incidence of hyperandrogenism (greasy skin, acne and hirsutism),
      evaluated by a specific questionnaire, was higher and statistically significant
      in MS patients than in controls (28% vs. 10%, p<0.05). Further studies, including
      a complete clinical and laboratory evaluation of gonadal function, are necessary
      in order to clarify whether hyperandrogenism may influence MS disease activity.

PMID- 11524632
TI  - Synthetic tetrapeptide epitalon restores disturbed neuroendocrine regulation in
      senescent monkeys.
AB  - The OBJECTIVE of this research was to investigate the regulatory effect of
      Epitalon on the production of melatonin and cortisol in senescent monkeys.
      MATERIAL AND METHODS: We investigated the character of melatonin and cortisol
      secretion by immunoferment assay in Epitalon-administered female Macaca mulatta
      in different age periods. RESULTS: Epitalon was proven to significantly stimulate
      melatonin synthesis in senescent monkeys in the evening, thereby normalising the
      circadian rhythm of cortisol secretion.

PMID- 11524633
TI  - Influence of pinealectomy and long-term melatonin administration on GH-IGF-I axis
      function in male rats.
AB  - BACKGROUND: A relationship between circadian GH-IGF-I axis activity and pineal
      gland function in rats is not sufficiently elucidated, particularly in the aspect
      of melatonin (MEL) participation with relation to a possible mechanism of these
      dependencies. OBJECTIVE: Influence of pinealectomy and long-term MEL
      administration on circadian GH-IGF-I axis function in male rats was evaluated. An
      attempt was also made to determine whether the effect of exogenous MEL is
      dependent on the pineal gland presence. METHODS: Studies were performed in 192
      sexually mature male Wistar rats, which were subjected to pinealectomy or sham
      operation. In half of the animals from each group MEL (Sigma, USA) in dose of 50
      microg/ 100g b.m. was administrated intraperitoneally (daily between 5 and 6 pm
      during a 4-week period). Blood for RIA assays of MEL, GH and IGF-I concentrations
      was collected every 3 hours during a day-beginning at 8 am (rats killed by
      decapitation). RESULTS: Significant influence of pinealectomy and exogenous MEL
      on a daily profile of endogenous MEL in rats was confirmed. Distinct, dependent
      on the time of the day anomalies in circadian oscillations of GH and IGF-I
      showing positive correlation with changes in endogenous MEL concentrations were
      also shown. GH rhythm was suppressed in a group of rats with removed pineal
      gland; after pinealectomy distinct decrease and after MEL use - distinct increase
      of GH and IGF-I concentrations during the day were observed. It had influenced
      mean daily concentrations and values of amplitude of circadian GH and IGF-I
      oscillations in all studied groups of animals. In rats with preserved pineal
      gland the effect of exogenous MEL action was more intensified. CONCLUSIONS:
      Pineal gland can influence circadian function of GH-IGF-I axis, and in mechanism
      of this dependence, changes in endogenous MEL concentrations seem to play an
      important role. Administration of MEL in rats after pinealectomy only partly
      prevents changes of GH-IGF-I axis function caused by gland removal, which can
      indicate participation of other pineal gland substances in generating
      disturbances. Influence of exogenous MEL on GH-IGF-I axis function during the day
      is dependent on the presence of pineal gland, which can be connected with
      indirect and/or direct influence of administrated hormone on this gland.

PMID- 11524634
TI  - Heterotopy of thyroid tissue--a modified therapeutical approach.
AB  - OBJECTIVES: The authors describe the classification of heterotopic thyroid
      tissue. A survey of more than 600 literature cases is provided. Different therapy
      approaches for these anomalies are discussed. Data from seven subsequent cases
      have been added to the existing literature data. The authors present an
      alternative approach to the therapy of heterotopic thyroid tissue. MATERIALS AND
      METHODS: The records of seven patients treated for a heterotopy of the thyroid
      tissue as the Department of ENT and Head and Neck Surgery of First Medical school
      of the Charles University of Prague since 1.1.1991 to 1.1.2001 have been
      analyzed. RESULTS: The first group: No surgery. This approach was used for
      children. In these patients the heterotopic thyroid tissue is the only thyroid
      tissue they have, but its function is not damaged and there are no mechanical
      symptoms (no airway obstruction and dysphagia). TSH substitution-suppression
      therapy is necessary for this group. Cooperation and follow up by the
      endocrinology, otolaryngology and pediatric departments is necessary. At a later
      age these patients can be treated as in the second group. The second group:
      Surgery. All patients in this group had heterotopic thyroid tissue. The total
      removal of thyroid tissue has been preferred. Carcinomatous change or the
      development of mechanical syndrome, dysphagia or airway obstruction is possible.
      Total removal is the best surgical approach. Various surgical methods are
      described in the literature (CO2 laser, intraoral, mandibulotomy, middle hyotomy
      etc.). These patients are treated as after total thyroidectomy and substitution
      therapy with synthetic thyroid hormones is necessary. The authors describe and
      add seven cases to the literature data. The authors describe radical removal of
      aberrant and accessory tissue [corrected].

PMID- 11524636
TI  - Philosophy behind science. Confirming affectivity, the dawn of human life: the
      pre-, peri- and postnatal affective-confirming. Haptonomic accompaniment of
      parents and their child.
AB  - This article gives a short introduction to the science of Haptonomy and more
      specially to the application of its specific phenomenality of psychotactile
      affective contact and interaction during prenatal and postnatal life and during
      childbirth. The neurophysiological implications and the influence of this
      approach on the pain threshold are briefly mentioned, as well as psychological
      influences on the postnatal development of the child. Finally, there is a
      critical commentary on the use of the ultra-sound scan.

PMID- 11524637
TI  - Electrophysiologic basis by which epinephrine facilitates defibrillation after
      prolonged episodes of ventricular fibrillation.
AB  - STUDY OBJECTIVE: Even though epinephrine has been shown to decrease the
      electrical stability of the heart, it is used extensively in cardiac
      resuscitation. The objective of this study is to document electrophysiologic
      parameters of epinephrine, which would facilitate defibrillation. METHODS: In 20
      swine, electrically induced ventricular fibrillation was allowed to continue for
      10 minutes. Animals were then randomly assigned to receive either intracardiac
      injection of 1 mg of epinephrine or 10 mL of normal saline solution.
      Synchronization and dispersion of the repolarization of fibrillatory waves and
      cycle length were measured. RESULTS: As the ventricular fibrillation continued,
      cycle length was prolonged, and synchronization and dispersion deteriorated. With
      epinephrine, cycle length shortened from 416+/-21 to 204+/-23 ms (P<.005),
      synchronization improved from 114+/-13 to 61+/-10 ms (P<.05), and dispersion
      narrowed from 84+/-10 to 49+/-8 ms (P<.005). Normal saline solution had no
      effect. Successful resuscitation was achieved in all 10 animals administered
      epinephrine and only 1 animal in the saline solution group. CONCLUSION:
      Epinephrine's effect on cycle length, synchronization, and dispersion of
      repolarization of fibrillatory waves may be the mechanism with which it
      facilitates defibrillation.

PMID- 11524638
TI  - Selective dual nuclear scanning in low-risk patients with chest pain to reliably
      identify and exclude acute coronary syndromes.
AB  - STUDY OBJECTIVE: We sought to determine the use in routine clinical practice of
      selective dual nuclear cardiac scanning (rest and stress) in low-risk patients
      with chest pain for identifying and excluding acute coronary syndromes (ACSs)
      during the initial emergency department evaluation. METHODS: A prospective
      observational study was conducted over 13 months in 1,775 low-risk patients with
      chest pain who had intermediate- and high-risk ACSs ruled out by means of our 2
      hour protocol, which consists of automated serial 12-lead ECG monitoring in
      conjunction with baseline and 2-hour creatine kinase (CK) MB and troponin I
      (cTnI) measurements. At the completion of the 2-hour evaluation period, low-risk
      patients were stratified by means of physician judgment into 1 of 2 categories:
      category III, possible ACS; and category IV, probable non-ACS chest pain. Level
      III patients underwent immediate dual nuclear scanning (rest thallium and stress
      sestamibi scanning), and level IV patients were discharged directly from the ED
      unless another serious non-ACS medical condition was thought to exist. Rest and
      stress scans were interpreted by a board-certified radiologist contemporaneous
      with patient evaluation. All patients were followed up for 30-day ACS, which was
      defined as acute myocardial infarction, percutaneous transluminal coronary
      angioplasty/coronary artery bypass grafting, coronary arteriography revealing
      stenosis of the major coronary artery of 70% or greater not amenable to
      percutaneous transluminal coronary angioplasty/coronary artery bypass grafting,
      life-threatening complication, or cardiac death within 30 days of ED
      presentation. RESULTS: A total of 2,206 ED patients with chest pain were
      evaluated for ACS during the study period. Four hundred thirty-one patients were
      excluded for having 1 or more of the following findings: initial ECG diagnostic
      of injury; baseline CK-MB level, cTnI level, or both diagnostic of acute
      myocardial infarction; 2-hour DeltaCK-MB level of +1.5 ng/mL or greater; 2-hour
      DeltacTnI level of +0.2 ng/mL or greater; injury or new or evolving ischemia on
      serial 12-lead ECG monitoring; or clinical diagnosis of ACS. Of the 1,775 study
      patients, 805 (45.4%) underwent immediate dual nuclear scanning. A positive
      stress nuclear scan result was more sensitive (97.3% versus 71.2%, P <.0001) and
      specific (87.7% versus 72.6%, P <.0001) for 30-day ACS than a positive resting
      nuclear scan result. The protocol of selective dual nuclear scanning (ie,
      patients who did not undergo dual nuclear scanning were counted as having a
      negative test result) had a sensitivity and specificity for 30-day ACS of 93.4%
      and 94.7%, respectively (positive likelihood ratio 17.6; negative likelihood
      ratio 0.07). CONCLUSION: Stress nuclear scanning is more sensitive and specific
      than resting nuclear scanning for identification of ACS in low-risk patients with
      chest pain. A strategy of using selective dual nuclear scanning once high- and
      intermediate-risk ACS has been ruled out with our 2-hour evaluation both reliably
      identifies and reliably excludes 30-day ACS.

PMID- 11524639
TI  - Training seniors in the operation of an automated external defibrillator: a
      randomized trial comparing two training methods.
AB  - STUDY OBJECTIVE: This study evaluated the differences in efficacy of 2 methods
      for training seniors in the use of an automated external defibrillator (AED). We
      tested the hypothesis that each training method (face-to-face instruction
      compared with video-based instruction) would result in similar AED performance on
      a manikin. METHODS: Two hundred ten seniors from various senior centers were
      randomized to receive face-to-face or video-based instruction on AED skills.
      Seniors were assessed individually and tested on the speed and quality of AED
      performance. We retested 177 of these initial trainees 3 months after initial
      training. Similar performance measures were assessed. RESULTS: Although there
      were statistically significant differences between the 2 training methods in
      terms of average time to shock at both evaluations, the results in general
      demonstrate that there were no clinically meaningful distinctions (time
      differences of <20 seconds) between the AED performance of seniors trained with a
      video and seniors trained in a face-to-face setting at the initial training or at
      the retention assessment. At the initial evaluation, overall performance was
      satisfactory, with greater than 98% trained with either method delivering a
      shock. However, at the 3-month follow-up, almost one fourth of trainees were not
      able to deliver a shock, and almost half were not able to correctly place the
      pads on the manikin. CONCLUSION: We believe that seniors can be trained equally
      well in AED performance with video-based self-instruction or face-to-face
      instruction. How to maintain acceptable AED performance skills over time remains
      a challenge.

PMID- 11524640
TI  - Soluble intercellular adhesion molecule-1 as a predictor of early adverse events
      in patients with chest pain compatible with myocardial ischemia.
AB  - STUDY OBJECTIVE: Inflammation plays an important role in acute coronary
      syndromes, and some evidence indicates that patients with a more pronounced
      vascular inflammatory response have a poorer outcome. Soluble intercellular
      adhesion molecule-1 (sICAM-1) is a specific marker for vascular endothelial cell
      activation. The aim of this study was to investigate the prognostic value of
      plasma sICAM-1 levels in patients with acute chest pain compatible with
      myocardial ischemia. METHODS: This prospective study was conducted at 2 urban
      university medical centers. The study cohort consisted of 119 consecutive
      patients with chest pain in whom myocardial ischemia was suspected clinically at
      presentation. Patients with conditions that affect sICAM-1 levels were
      ineligible. Cardiac troponin I (cTnI), C-reactive protein, and sICAM-1 levels
      were assayed at presentation to the emergency department. The primary end point
      was the occurrence of a serious cardiac event (death, nonfatal acute myocardial
      infarction, coronary revascularization) in the hospital. RESULTS: Although sICAM
      1 levels tended to be higher in patients with a serious cardiac event, there was
      no significant association. In contrast, a cTnI level greater than 0.2 ng/mL was
      a powerful predictor of an in-hospital serious cardiac event (odds ratio 16.3,
      95% confidence interval [CI] 4.7 to 55.9; P <.0001). Soluble ICAM-1 levels of
      more than 260 ng/mL at presentation had a sensitivity for predicting a serious
      cardiac event of 63% (95% CI 46% to 81%) but a specificity of only 47% (95% CI
      38% to 57%). CONCLUSION: In a heterogeneous population of patients with chest
      pain compatible with myocardial ischemia, elevated sICAM-1 levels are poor
      predictors of an individual patient suffering a serious cardiac event in the
      hospital.

PMID- 11524641
TI  - 2000 ACC/AHA guidelines for the management of patients with unstable angina and
      non-ST-segment elevation myocardial infarction: a practical summary for emergency
      physicians.
AB  - There have been numerous significant clinical advances in both the diagnosis and
      therapy of acute coronary syndrome during the past several years. Even the term
      "acute coronary syndrome" is a recent creation meant to expand clinical attention
      in patients with chest pain of coronary origin beyond identification of ST
      segment elevation myocardial infarction and prompt initiation of reperfusion
      therapy and to include the evaluation and management of those patients with
      unstable angina (UA) or myocardial injury that does not cause ST-segment
      elevation. Many of these advances have been studied and first implemented outside
      the emergency department, leading some emergency physicians to be slow to embrace
      them, and leaving others without a viable practical option to use them outside of
      the cardiac catheterization laboratory or the coronary care unit. In September
      2000, the American College of Cardiology and the American Heart Association
      issued practice guidelines for the care of patients with UA and non-ST-segment
      elevation myocardial infarction. The guidelines specifically address the
      diagnosis and management of UA and non-ST-segment elevation myocardial infarction
      in the ED, suggesting evidence-based standards for risk stratification, for the
      use of biologic markers of myocardial damage and other adjunctive diagnostic
      tests, and for the appropriate use of antiplatelet and antithrombin therapeutic
      agents. This article provides an overview of the ED-pertinent analyses and
      recommendations from the 93-page document. A commentary on the implementation of
      these recommendations in the ED follows in a separate article.

PMID- 11524642
TI  - Advances create opportunities: implementing the major tenets of the new unstable
      angina guidelines in the emergency department.
AB  - Of all the clinical syndromes with which emergency physicians must deal, chest
      pain of coronary cause has benefited from the most striking recent advances both
      in diagnostic approach (cognitive and technologic) and in therapeutic options.
      Chest pain evaluation and management have become important foci of research in
      emergency medicine, and entire units are dedicated to its clinical prosecution in
      emergency departments and elsewhere in the hospital. New diagnostic tools are
      proposed and studied on a regular basis. Antiplatelet, antithrombin, and
      fibrinolytic agents unknown in clinical practice as recently as 5 years ago have
      secured places in the emergency physician's armamentarium for treating acute
      coronary syndrome. Many of these diagnostic and therapeutic tools have been
      developed in the coronary care unit and in the cardiac catheterization
      laboratory. Although intuitively they may also be useful outside of those
      settings, they have unreliably been brought to the ED for implementation and
      resultant appropriate prompt and early care of the coronary patient who does not
      meet fibrinolytic criteria. As emergency physicians seek to bring accurate chest
      pain risk stratification into their practice and begin to use new therapeutic
      agents to minimize myocardial damage before turning the patient's care over to
      other specialists, it is essential that they are familiar with the data
      supporting these approaches. In this commentary, we seek to place the American
      College of Cardiology/American Heart Association unstable angina guidelines into
      the clinical context of the ED.

PMID- 11524643
TI  - Platelet glycoprotein inhibitors in patients with medically managed acute
      coronary syndrome: does the enthusiasm exceed the science?
AB  - Guidelines from the American Heart Association and the American College of
      Cardiology, as well as numerous review articles, have strongly and
      enthusiastically recommended that platelet glycoprotein IIb/IIIa inhibitors be
      used in patients with medically managed unstable angina or non-ST-segment
      myocardial infarction (UA/NSTEMI). We explore whether there is sufficient
      experimental evidence to justify these recommendations. We review the 4 large
      randomized trials of US Food and Drug Administration-approved platelet
      glycoprotein IIb/IIIa inhibitors that included medically managed UA/NSTEMI
      patients, first taking each trial's results at face value and then in the context
      of likely biases. The risk differences, unadjusted for potential biases, are 2.5%
      (0.6%, 4.4%) for the Platelet Receptor Inhibition in Ischemic Syndrome Management
      (PRISM) study, 2.3% (-1.9%, 6.5%) for the Platelet Receptor Inhibition in
      Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms
      (PRISM-PLUS) study (tirofiban plus heparin), 0.9% (-0.9%, 2.8%) for the Platelet
      Glycoprotein IIb/IIIa in Unstable Angina Receptor Suppression Using Integrilin
      Therapy (PURSUIT) trial, -0.2% (-1.7%, 1.3%) for the least harmful treatment arm
      of the Global Utilization of Streptokinase and Tissue Plasminogen Activator for
      Occluded Coronary Arteries (GUSTO-IV) trial, and -1.9% (-6.8%, 3.0%) for the
      PRISM-PLUS study (tirofiban alone) (positive numbers indicate benefit). The 95%
      confidence interval produced by combining the studies using a random effects
      model is -1.3% to 3.2% (mean 0.9%); this is consistent with drugs providing a
      small benefit, no benefit, or causing harm. Confounding caused by the nonrandom
      selection of patients for percutaneous transluminal coronary angioplasty and
      coronary artery bypass grafting in all trials except GUSTO-IV and problems
      arising from the fact that enrolled patients were much sicker than typical
      UA/NSTEMI patients are likely to have biased the studies away from the null and
      make an assertion of benefit even more tenuous. Given the equivocal results, it
      would appear that the authors are relying on opinion rather than evidence to
      formulate their conclusions. Clinicians should understand that opinion and
      factors other than medical evidence may influence the content of the
      recommendations.

PMID- 11524644
TI  - Out-of-hospital defibrillation with automated external defibrillators: postshock
      analysis should be delayed.
AB  - STUDY OBJECTIVE: The American Heart Association protocols for use of automated
      external defibrillators (AEDs) recommend that a rhythm analysis be done
      immediately after each defibrillation attempt. However, shock is often followed
      by electrical silence or marginally organized electrical activity before
      ventricular fibrillation (VF) or ventricular tachycardia (VT) recurs. The optimal
      timing of postshock analysis for identification of recurrent VF/VT is unknown.
      This study examines the time to recurrence of VF/VT after a defibrillation
      attempt with AED. METHODS: Over an 18-month period, all tapes from patients with
      out-of-hospital cardiac arrest who received shocks at least once with an AED were
      screened for recurrent VF/VT. All cases come from a single emergency medical
      services system providing basic life support, defibrillation with AED, and
      intubation with an esophageal-tracheal twin-lumen airway device (Combitube) for a
      population of 633,511 individuals. Pediatric and traumatic cases were excluded.
      When VF/VT recurred within 3 minutes of the defibrillation attempt, rhythm strips
      were printed and included in the study. Two cardiology fellows, blinded to the
      study objectives, measured the time from defibrillation to recurrent VF/VT for
      each strip. RESULTS: Over the study period, 222 tapes from 96 patients met the
      inclusion criteria. Only 44 (20%) occurrences of VF/VT had recurred within 6
      seconds of defibrillation, 162 (73%) at 60 seconds, and 200 (90%) at 90 seconds.
      CONCLUSION: Eighty percent of VF/VT recurred more than 6 seconds after
      defibrillation and were missed when using current American Heart Association AED
      protocols. Subsequent analysis should be postponed until at least 30 seconds
      after defibrillation. Performing 30 seconds of chest compressions after
      defibrillation before subsequent AED rhythm analysis would increase AED
      identification of VF/VT to 52%.

PMID- 11524645
TI  - Performance and error analysis of automated external defibrillator use in the out
      of-hospital setting.
AB  - STUDY OBJECTIVE: We determined whether automated external defibrillators (AEDs)
      can meet the American Heart Association performance criteria to detect and shock
      unstable cardiac rhythms (ventricular fibrillation [VF], ventricular tachycardia
      [VT]) in the setting of an out-of-hospital cardiac arrest. METHODS: AED
      performance was reviewed for cardiac arrests occurring between January 1, 1995,
      and December 31, 1997. After every cardiac arrest, data regarding each rhythm
      analyzed and subsequent response (shock or no shock) were downloaded from the AED
      memory module. The study paramedic and study physician independently reviewed
      each case and interpreted cardiac rhythms from downloaded AED data. The emergency
      medical services medical director resolved all discrepancies in a blinded manner.
      All cases of out-of-hospital cardiac arrest in which an AED was turned on and a
      rhythm analyzed were included. The primary objective was the correct
      identification and defibrillation of VF or VT. Sensitivity, specificity, and
      predictive values with 95% confidence intervals (CIs) were calculated. Sources of
      error in AED rhythm management are also described. RESULTS: A total of 3,448 AED
      rhythms were available for interpretation. Sensitivity and specificity for
      appropriate AED management of a shockable (VF or VT) rhythm were 81.0% (95% CI
      77.9% to 83.8%) and 99.9% (95% CI 99.7% to 100%), respectively. Positive and
      negative predictive values were 99.6% (95% CI 98.7% to 99.9%) and 95.5% (95% CI
      94.7% to 96.2%), respectively. There were 132 errors associated with AED
      management. Two errors resulted in delivery of an inappropriate shock. In the
      remaining 130 errors, a shockable rhythm was not shocked. Fifty-five (42.3%)
      errors were AED dependent, 70 (53.9%) were operator dependent, and 5 (3.9%) were
      unclassified. CONCLUSION: The AED had high specificity and moderately high
      sensitivity in detecting and shocking unstable cardiac rhythms in the out-of
      hospital setting. Few cardiac rhythms were mismanaged by the AED. Elimination of
      operator-dependent errors could increase AED sensitivity.

PMID- 11524646
TI  - Can paramedics using guidelines accurately triage patients?
AB  - STUDY OBJECTIVE: We determine whether paramedics, using written guidelines, can
      accurately triage patients in the field. METHODS: This prospective, descriptive
      study was conducted at an urban county emergency medical services (EMS) system
      and county hospital. Paramedics triaged patients, for study purposes only,
      according to 4 categories: (1) needing to come to the emergency department by
      advanced life support (ALS) transport, (2) needing to come to the ED by any
      transport, (3) needing to see a physician within 24 hours, or (4) not needing any
      further physician evaluation. Medical records that provided patient treatment
      information to the point of ED disposition were subsequently reviewed (blinded to
      the paramedic rating) to determine which of the categories was appropriate. The
      protocol of the EMS system of the study site dictates that all patients should be
      transported except for those who refuse care and leave against medical advice.
      Only transported patients were included in the present study. Fifty-four
      paramedics triaged 1,180 patients. RESULTS: Mean patient age was 43.4+/-17 years;
      62.0% were male. Paramedics rated 1,000 (84.7%) of the patients as needing to
      come to the ED and 180 (15.3%) as not needing to come to the ED. Ratings
      according to triage category were as follows: 804 (68.1%) category 1, 196 (16.6%)
      category 2, 148 (12.5%) category 3, and 32 (2.7%) category 4. Seven hundred
      thirty-six (62.4%) patients were discharged, 298 (25.3%) were admitted, 90 (7.6%)
      were transferred, 36 (3.1%) left against medical advice, and 20 (1.7%) died. The
      review panel determined that 113 (9.6%) patients were undertriaged; 55 (48.7%) of
      these patients were misclassified because the paramedics misused the guidelines.
      Ninety-nine patients (8.4% of the total sample) were incorrectly classified as
      not needing to come to the ED. This represented 55% of the patients (99/180)
      categorized as 3 or 4 by the paramedics. Fourteen patients (1.2% of total) were
      incorrectly classified as category 4 instead of 3. Of the 113 undertriaged
      patients, 22 (19.6%) were admitted, 86 (76.1%) were discharged, and 4 (3.5%) were
      transferred. CONCLUSION: Paramedics using written guidelines fall short of an
      acceptable level of triage accuracy to determine disposition of patients in the
      field.

PMID- 11524647
TI  - To shock or not to shock: that is the question.

PMID- 11524649
TI  - Applying information technology to the problem of acute myocardial infarction
      access to care, diagnosis, and evaluation: report of a symposium.

PMID- 11524651
TI  - Data standards in health care.

PMID- 11524648
TI  - Undertriage, overtriage, or no triage? In search of the unnecessary emergency
      department visit.

PMID- 11524652
TI  - Confidentiality and medical information.

PMID- 11524650
TI  - Telecommunications and the next generation internet for health care.

PMID- 11524653
TI  - Canadian CT head rule study for patients with minor head injury: methodology for
      phase II (validation and economic analysis).
AB  - Prospective validation on a new set of patients is an essential test of a new
      decision rule. However, many clinical decision rules are not prospectively
      assessed to determine their accuracy, reliability, clinical sensibility, or
      potential impact on practice. This validation process is important because many
      statistically derived rules or guidelines do not perform well when tested in a
      new population. The methodologic standards for a validation study are similar to
      those described in the article on phase I for derivation studies in the August
      2001 issue of Annals of Emergency Medicine. The goal of phase II is to
      prospectively assess the accuracy, reliability, and acceptability of the decision
      rule in a new set of patients with minor head injury. This will determine the
      clinical utility of the rule and is essential if such a rule is to be widely
      adopted into clinical practice.

PMID- 11524655
TI  - Use of the intra-aortic balloon pump to stop gastrointestinal bleeding.
AB  - Temporary aortic occlusion can be lifesaving in selected conditions. We describe
      the unorthodox use of an intra-aortic balloon pump without counterpulsation to
      achieve temporary vascular control in a patient with shock caused by rapid upper
      gastrointestinal bleeding. The technique of aortic balloon occlusion has been
      reported in several clinical circumstances, primarily trauma. However, its use to
      increase blood pressure and gain time for resuscitation before laparotomy for
      catastrophic gastrointestinal bleeding has not previously been described.

PMID- 11524654
TI  - Emergency medical care in rural America.
AB  - The delivery of high-quality emergency care in a rural setting requires a
      conceptual framework quite different from that required in urban and suburban
      environments, given that available resources are limited in the rural setting.
      The intermittent and episodic nature of seriously ill and injured patients who
      present to rural emergency departments makes it difficult to plan, staff, and
      equip in order to provide emergency medical care at the same level seen at higher
      volume urban or suburban institutions. The objective of this article is to
      describe the distinctive nature and widely unrecognized features of emergency
      medicine in rural and remote areas, with a focus on clinical, workforce, and
      economic issues. We present recommendations for a shift in thinking and a call to
      action on behalf of all emergency medicine professionals that are based on a
      realistic assessment of the current status of emergency medicine and that are
      needed to develop and sustain high-quality emergency medical care in rural
      America.

PMID- 11524656
TI  - Acute monocular blindness associated with spontaneous common carotid artery
      dissection.
AB  - The evaluation of patients with loss of vision is common in the emergency
      department. Central retinal artery occlusion (CRAO) is a potentially reversible
      cause of acute monocular blindness. When evaluating a patient with CRAO, the
      potential underlying causes should be considered while simultaneously initiating
      treatment. We present a case of spontaneous common carotid artery dissection
      manifesting as CRAO and propose that spontaneous carotid artery dissection be
      included in the differential diagnosis of CRAO.

PMID- 11524657
TI  - Enriching the resident-faculty relationship.

PMID- 11524659
TI  - Annie.

PMID- 11524658
TI  - Update: Multistate outbreak of listeriosis--United States, 2000.

PMID- 11524660
TI  - Admission.

PMID- 11524661
TI  - Two cases of withdrawal from 1,4-Butanediol use.

PMID- 11524662
TI  - Use of physostigmine in the management of gamma-hydroxybutyrate overdose.

PMID- 11524663
TI  - Provider risk during medically futile emergency department thoracotomy.

PMID- 11524664
TI  - Healthy debate of structural analysis.

PMID- 11524665
TI  - The C-terminus of p53: the more you learn the less you know.

PMID- 11524666
TI  - How to make a metalloprotein.

PMID- 11524667
TI  - Actin allostery again?

PMID- 11524668
TI  - The lysozyme mechanism sorted -- after 50 years.

PMID- 11524669
TI  - Action at the assemblin dimer interface.

PMID- 11524670
TI  - Hydrogen exchange.

PMID- 11524671
TI  - Picture story. Chipping away at the proteome's mysteries.

PMID- 11524672
TI  - An elusive propeller-like fold.

PMID- 11524674
TI  - RNA interference: listening to the sound of silence.
AB  - The term RNA interference (RNAi) describes the use of double-stranded RNA to
      target specific mRNAs for degradation, thereby silencing their expression. RNAi
      is one manifestation of a broad class of RNA silencing phenomena that are found
      in plants, animals and fungi. The discovery of RNAi has changed our understanding
      of how cells guard their genomes, led to the development of new strategies for
      blocking gene function, and may yet yield RNA-based drugs to treat human disease.

PMID- 11524675
TI  - Heterodimeric structure of superoxide dismutase in complex with its
      metallochaperone.
AB  - The copper chaperone for superoxide dismutase (CCS) activates the eukaryotic
      antioxidant enzyme copper, zinc superoxide dismutase (SOD1). The 2.9 A resolution
      structure of yeast SOD1 complexed with yeast CCS (yCCS) reveals that SOD1
      interacts with its metallochaperone to form a complex comprising one monomer of
      each protein. The heterodimer interface is remarkably similar to the SOD1 and
      yCCS homodimer interfaces. Striking conformational rearrangements are observed in
      both the chaperone and target enzyme upon complex formation, and the functionally
      essential C-terminal domain of yCCS is well positioned to play a key role in the
      metal ion transfer mechanism. This domain is linked to SOD1 by an intermolecular
      disulfide bond that may facilitate or regulate copper delivery.

PMID- 11524676
TI  - Latent and active p53 are identical in conformation.
AB  - p53 is a nuclear phosphoprotein that regulates cellular fate after genotoxic
      stress through its role as a transcriptional regulator of genes involved in cell
      cycle control and apoptosis. The C-terminal region of p53 is known to negatively
      regulate sequence specific DNA-binding of p53; modifications to the C-terminus
      relieve this inhibition. Two models have been proposed to explain this latency:
      (i) an allosteric model in which the C-terminal domain interacts with another
      domain of p53 or (ii) a competitive model in which the C-terminal and the core
      domains compete for DNA binding. We have characterized latent and active forms of
      dimeric p53 using gel mobility shift assays and NMR spectroscopy. We show on the
      basis of chemical shifts that dimeric p53 both containing and lacking the C
      terminal domain are identical in conformation and that the C-terminus does not
      interact with other p53 domains. Similarly, NMR spectra of isolated core and
      tetramerization domains confirm a modular p53 architecture. The data presented
      here rule out an allosteric model for the regulation of p53.

PMID- 11524677
TI  - Structure of the DLM-1-Z-DNA complex reveals a conserved family of Z-DNA-binding
      proteins.
AB  - The first crystal structure of a protein, the Z alpha high affinity binding
      domain of the RNA editing enzyme ADAR1, bound to left-handed Z-DNA was recently
      described. The essential set of residues determined from this structure to be
      critical for Z-DNA recognition was used to search the database for other proteins
      with the potential for Z-DNA binding. We found that the tumor-associated protein
      DLM-1 contains a domain with remarkable sequence similarities to Z alpha(ADAR).
      Here we report the crystal structure of this DLM-1 domain bound to left-handed Z
      DNA at 1.85 A resolution. Comparison of Z-DNA binding by DLM-1 and ADAR1 reveals
      a common structure-specific recognition core within the binding domain. However,
      the domains differ in certain residues peripheral to the protein-DNA interface.
      These structures reveal a general mechanism of Z-DNA recognition, suggesting the
      existence of a family of winged-helix proteins sharing a common Z-DNA binding
      motif.

PMID- 11524678
TI  - Transition states and the meaning of Phi-values in protein folding kinetics.
AB  - What is the mechanism of two-state protein folding? The rate-limiting step is
      typically explored through a Phi-value, which is the mutation-induced change in
      the transition state free energy divided by the change in the equilibrium free
      energy of folding. Phi-values ranging from 0 to 1 have been interpreted as
      meaning the transition state is denatured-like (0), native-like (1) or in
      between. But there is no classical interpretation for the experimental Phi-values
      that are negative or >1. Using a rigorous method to identity transition states
      via an exact lattice model, we find that nonclassical Phi-values can arise from
      parallel microscopic flow processes, such as those in funnel-shaped energy
      landscapes. Phi < 0 results when a mutation destabilizes a slow flow channel,
      causing a backflow into a faster flow channel. Phi > 1 implies the reverse: a
      backflow from a fast channel into a slow one. Using a 'landscape mapping' method,
      we find that Phi correlates with the acceleration/deceleration of folding induced
      by mutations, rather than with the degree of nativeness of the transition state.

PMID- 11524679
TI  - Crystal structure of the human prion protein reveals a mechanism for
      oligomerization.
AB  - The pathogenesis of transmissible encephalopathies is associated with the
      conversion of the cellular prion protein, PrP(C), into a conformationally altered
      oligomeric form, PrP(Sc). Here we report the crystal structure of the human prion
      protein in dimer form at 2 A resolution. The dimer results from the three
      dimensional swapping of the C-terminal helix 3 and rearrangement of the disulfide
      bond. An interchain two-stranded antiparallel beta-sheet is formed at the dimer
      interface by residues that are located in helix 2 in the monomeric NMR
      structures. Familial prion disease mutations map to the regions directly involved
      in helix swapping. This crystal structure suggests that oligomerization through
      3D domain-swapping may constitute an important step on the pathway of the PrP(C) 
      -> PrP(Sc) conversion.

PMID- 11524680
TI  - Characterization of a cellulosome dockerin domain from the anaerobic fungus
      Piromyces equi.
AB  - The recycling of photosynthetically fixed carbon in plant cell walls is a key
      microbial process. In anaerobes, the degradation is carried out by a high
      molecular weight multifunctional complex termed the cellulosome. This consists of
      a number of independent enzyme components, each of which contains a conserved
      dockerin domain, which functions to bind the enzyme to a cohesin domain within
      the protein scaffoldin protein. Here we describe the first three-dimensional
      structure of a fungal dockerin, the N-terminal dockerin of Cel45A from the
      anaerobic fungus Piromyces equi. The structure contains a novel fold of 42
      residues. The ligand binding site consists of residues Trp 35, Tyr 8 and Asp 23,
      which are conserved in all fungal dockerins. The binding site is on the opposite
      side of the N- and C-termini of the molecule, implying that tandem dockerin
      domains, seen in the majority of anaerobic fungal plant cell wall degrading
      enzymes, could present multiple simultaneous binding sites and, therefore, permit
      tailoring of binding to catalytic demands.

PMID- 11524681
TI  - Crystal structure of Mip, a prolylisomerase from Legionella pneumophila.
AB  - The human pathogen Legionella pneumophila, the etiological agent of the severe
      and often fatal Legionnaires' disease, produces a major virulence factor, termed
      'macrophage infectivity potentiator protein' (Mip), that is necessary for optimal
      multiplication of the bacteria within human alveolar macrophages. Mip exhibits a
      peptidyl prolyl cis-trans isomerase (PPIase) activity, which appears to be
      important for infection. Here we report the 2.4 A crystal structure of the Mip
      protein from L. pneumophila Philadelphia 1 and the 3.2 A crystal structure of its
      complex with the drug FK506. Each monomer of the homodimeric protein consists of
      an N-terminal dimerization module, a long (65 A) connecting alpha-helix and a C
      terminal PPIase domain exhibiting similarity to human FK506-binding protein. In
      view of the recent significant increase in the number of reported cases of
      Legionnaires' disease and other intracellular infections, these structural
      results are of prime interest for the design of new drugs directed against Mip
      proteins of intracellular pathogens.

PMID- 11524682
TI  - Crystal structure of the APC10/DOC1 subunit of the human anaphase-promoting
      complex.
AB  - The anaphase-promoting complex (APC), or cyclosome, is a cell cycle-regulated
      ubiquitin ligase that controls progression through mitosis and the G1 phase of
      the cell cycle. The APC is composed of at least 11 subunits; no structure has
      been determined for any of these subunits. The subunit APC10/DOC1, a one-domain
      protein consisting of 185 amino acids, has a conserved core (residues 22-161)
      that is homologous to domains found in several other putative ubiquitin ligases
      and, therefore, may play a role in ubiquitination reactions. Here we report the
      crystal structure of human APC10 at 1.6 A resolution. The core of the protein is
      formed by a beta-sandwich that adopts a jellyroll fold. Unexpectedly, this
      structure is highly similar to ligand-binding domains of several bacterial and
      eukaryotic proteins, such as galactose oxidase and coagulation factor Va, raising
      the possibility that APC10 may function by binding a yet unidentified ligand. We
      further provide biochemical evidence that the C-terminus of APC10 binds to
      CDC27/APC3, an APC subunit that contains multiple tetratrico peptide repeats.

PMID- 11524684
TI  - Manipulation of ligand binding affinity by exploitation of conformational
      coupling.
AB  - Traditional approaches for increasing the affinity of a protein for its ligand
      focus on constructing improved surface complementarity in the complex by altering
      the protein binding site to better fit the ligand. Here we present a novel
      strategy that leaves the binding site intact, while residues that allosterically
      affect binding are mutated. This method takes advantage of conformationally
      distinct states, each with different ligand-binding affinities, and manipulates
      the equilibria between these conformations. We demonstrate this approach in the
      Escherichia coli maltose binding protein by introducing mutations, located at
      some distance from the ligand binding pocket, that sterically affect the
      equilibrium between an open, apo-state and a closed, ligand-bound state. A family
      of 20 variants was generated with affinities ranging from an approximately 100
      fold improvement (7.4 nM) to an approximately two-fold weakening (1.8 mM)
      relative to the wild type protein (800 nM).

PMID- 11524683
TI  - Crystal structure and functional analysis of the SurE protein identify a novel
      phosphatase family.
AB  - Homologs of the Escherichia coli surE gene are present in many eubacteria and
      archaea. Despite the evolutionary conservation, little information is available
      on the structure and function of their gene products. We have determined the
      crystal structure of the SurE protein from Thermotoga maritima. The structure
      reveals the dimeric arrangement of the subunits and an active site around a bound
      metal ion. We also demonstrate that the SurE protein exhibits a divalent metal
      ion-dependent phosphatase activity that is inhibited by vanadate or tungstate. In
      the vanadate- and tungstate-complexed structures, the inhibitors bind adjacent to
      the divalent metal ion. Our structural and functional analyses identify the SurE
      proteins as a novel family of metal ion-dependent phosphatases.

PMID- 11524685
TI  - Structure is lost incrementally during the unfolding of barstar.
AB  - Coincidental equilibrium unfolding transitions observed by multiple structural
      probes are taken to justify the modeling of protein unfolding as a two-state, N
      <==> U, cooperative process. However, for many of the large number of proteins
      that undergo apparently two-state equilibrium unfolding reactions, folding
      intermediates are detected in kinetic experiments. The small protein barstar is
      one such protein. Here the two-state model for equilibrium unfolding has been
      critically evaluated in barstar by estimating the intramolecular distance
      distribution by time-resolved fluorescence resonance energy transfer (TR-FRET)
      methods, in which fluorescence decay kinetics are analyzed by the maximum entropy
      method (MEM). Using a mutant form of barstar containing only Trp 53 as the
      fluorescence donor and a thionitrobenzoic acid moiety attached to Cys 82 as the
      fluorescence acceptor, the distance between the donor and acceptor has been shown
      to increase incrementally with increasing denaturant concentration. Although
      other probes, such as circular dichroism and fluorescence intensity, suggest that
      the labeled protein undergoes two-state equilibrium unfolding, the TR-FRET probe
      clearly indicates multistate equilibrium unfolding. Native protein expands
      progressively through a continuum of native-like forms that achieve the
      dimensions of a molten globule, whose heterogeneity increases with increasing
      denaturant concentration and which appears to be separated from the unfolded
      ensemble by a free energy barrier.

PMID- 11524686
TI  - Structure of the rgRGS domain of p115RhoGEF.
AB  - p115RhoGEF, a guanine nucleotide exchange factor for Rho GTPase, is also a GTPase
      activating protein (GAP) for G(12) and G(13) heterotrimeric G alpha subunits.
      Near its N-terminus, p115RhoGEF contains a domain (rgRGS) with remote sequence
      identity to RGS (regulators of G protein signaling) domains. The rgRGS domain is
      necessary but not sufficient for the GAP activity of p115RhoGEF. The 1.9 A
      resolution crystal structure of the rgRGS domain shows structural similarity to
      RGS domains but possesses a C-terminal extension that folds into a layer of
      helices that pack against the hydrophobic core of the domain. Mutagenesis
      experiments show that rgRGS may form interactions with G alpha(13) that are
      analogous to those in complexes of RGS proteins with their G alpha substrates.

PMID- 11524687
TI  - Molecular mechanism for dimerization to regulate the catalytic activity of human
      cytomegalovirus protease.
AB  - Biochemical studies indicate that dimerization is required for the catalytic
      activity of herpesvirus proteases, whereas structural studies show a complete
      active site in each monomer, away from the dimer interface. Here we report
      kinetic, biophysical and crystallographic characterizations of structure-based
      mutants in the dimer interface of human cytomegalovirus (HCMV) protease. Such
      mutations can produce a 1,700-fold reduction in the kcat while having minimal
      effects on the K(m). Dimer stability is not affected by these mutations,
      suggesting that dimerization itself is insufficient for activity. There are large
      changes in monomer conformation and dimer organization of the apo S225Y mutant
      enzyme. However, binding of an activated peptidomimetic inhibitor induced a
      conformation remarkably similar to the wild type protease. Our studies suggest
      that appropriate dimer formation may be required to indirectly stabilize the
      protease oxyanion hole, revealing a novel mechanism for dimerization to regulate
      enzyme activity.

PMID- 11524691
TI  - [Test objects for Doppler sonography - What are their practical applications?].

PMID- 11524692
TI  - [Simulation of the heart action: a computer controlled module for the generation
      of variable flow patterns].
AB  - AIM: The development of a computer controlled pump for the generation of variable
      flow patterns with high reproducibility for simulating the haemodynamics in
      physiological model circuits. MATERIAL AND METHODS: The module is controlled by
      an arbitrary function generator. The shape of the flow profile is generated on
      the PC based on mathematical functions or drawn by hand. The amplified signal
      drives a DC motor which is coupled magnetically to a geared pumphead. The lack of
      mechanical coupling ensures smooth running and a complete attenuation of motor
      vibrations as well as a disturbance-free flow profile. The spectra were analyzed
      by Doppler-sonography with a 5 - 12 MHz linear probe and with pressure sensors.
      Silicon tubes were used as simulated vessels and a water-glycerine mixture with
      particles of cellulose as simulated blood. RESULTS: The generated flow patterns
      (constant flow and multi-phase patterns) correlate highly with the measured
      pressure- and velocity profiles. CONCLUSION: The variability and high
      reproducibility of the flow profiles and the realtime control of the signal
      parameters make the simulation of dynamic processes and haemodynamic long-time
      studies feasible. The module developed facilitates detailed studies of high
      reproducibility with physiological and pathological flow models and with
      simulated blood.

PMID- 11524693
TI  - [Improved ultrasound imaging of the pancreas with the transsplenic view and
      Tissue harmonic imaging].
AB  - The conventional ultrasound examination of the pancreas from ventral is -
      especially concerning the leftsided parts of the organ - limited by interposition
      of stomach, flexura duodenojejunalis or colon. The transsplenic view to the cauda
      pancreatis is less known, but allows quite often a good possibility to examine
      this part of the retroperitoneal organ, even when examination from ventral is
      impossible. AIM: Comparison of ventral and transsplenic ultrasound examination -
      with and without tissue harmonic imaging (THI) - in regard to the diagnostic
      accessability to the cauda pancreatis. METHOD: Ultrasound examination of 135
      patients from both positions with and without THI and comparison of the
      accessability by experienced examiners. RESULTS: As examination from the ventral
      position allows a proper view to the cauda only in 58 %, the transsplenic
      position allows an adequate view in 98 %. The examiners regarded THI as a useful
      improvement in examining the pancreas in 85 %. CONCLUSION: The transsplenic view
      to the pancreas is less known than the examination from the classical ventral
      transducer position. It enables the examinator quite often to examine the
      pancreatic cauda even when examination from ventral is impossible. Therefore it
      should be enclosed in the routine procedure of abdominal ultrasound examination.
      THI is a further possibility to improve the ultrasound access to the pancreas,
      especially when conditions for a good view and proper examination are limited.

PMID- 11524694
TI  - [Comparison of sonographic weight estimation to actual birth weight: a
      retrospective analysis].
AB  - AIM: This retrospective study aims at determining the accuracy of sonographic
      estimation of birth weight based on ultrasound examinations performed at the
      department of gynaecology of Philipps University at Marburg, Germany. METHOD: 630
      children were born at the university department of gynaecology during the first
      six months of 1998. 519 babies had been examined sonographically and their birth
      weight estimated within ten days prior to delivery. 176 (33,91 %) of these
      examinations were carried out by experienced sonographers complying to the level
      II standard of performance set out by DEGUM. 343 (66.09 %) of examinations were
      performed by less experienced junior doctors at the time of the mothers'
      admission to the delivery room. Two reference tables published by Hansmann und
      Ferrero were used to estimate birth weight. RESULTS: The lower and upper quartile
      of deviation between estimated weight and actual weight came to -200 g and + 200
      g using the Hansmann method and -180 g and + 220 g respectively based on the
      method of Ferrero. It has to be noted that even greater differences occurred: the
      10 % least exact estimates deviated by 500 g and more. The difference between
      estimated and actual weight increased with the length of pregnancy. The fully
      trained physician (DEGUM II) tended to estimate the birth weight more accurately.
      The average birth weight estimated sonographically was lower in "DEGUM II-babies"
      than that of children whose weight was estimated at the point of admission to the
      delivery room (Mann-Whitney p < 0,0001). Junior doctors showed a tendency to over
      estimate the birth weight of babies actually being underweight. The opposite
      happened with babies who presented a relatively higher birth weight: their
      projected birth weight was underestimated. On the other hand, the regression line
      of the sonographic estimations of birth weight performed by the expert (level II
      DEGUM) fit to the expected bisector of the angle (Passing-Bablock p > 0,05).
      CONCLUSION: When clinical decisions are based on estimated values of birth
      weight, the possible deviation of this value from the actual weight has to be
      taken into account. In our study this difference came up to 500 g independent of
      the level of the examiner's ultrasonographic training.

PMID- 11524695
TI  - [Sonographic imaging of upper eyelid tarsal radii when changing the direction of
      vision].
AB  - AIM: Aesthetic and reconstructive surgery of the upper eyelid attempts to restore
      aesthetic or functional deficits. Knowing of the anatomic relationships in these
      structures is very important. The aim of our study was to assess by ultrasound
      the upper eye lid tarsal curvature changes depending on movement of the bulbus.
      METHODS: In 50 people with healthy eyes we measured the diameter of the upper
      eyelid tarsal plate, the cornea, the bulbus and additionally the intraocular
      pressure. In measuring the upper eyelid tarsal plate we used transpalpebral
      ultrasound in a non contact mode with a 7.5 MHz linear array scanner, with the
      bulbus in median and in abduction position. RESULTS: In healthy eyes the diameter
      of the upper eye lid tarsal plate changes depend on movement of the bulbus. The
      mean diameter of the upper eye lid tarsal plate over the bulbus in medium
      position was 19.3 +/- 3.8 mm versus 30.1 +/- 6.3 mm in abduction position. This
      difference is statistically significant (p < 0.05). CONCLUSIONS: The results of
      the study indicate, that using ultrasound with a 7.5 MHz linear array scanner is
      appropriate for objective evaluation of relative changings of the upper eye lid
      tarsal plate diameter. The obtained data showed significant differences and must
      be taken into account when considering cosmetic and functional surgery of the
      upper eye lid, f. e. lidloading in facial palsy with gold or platinum implants.

PMID- 11524696
TI  - [Sonographic variability of lactating adenoma demonstrated by a longitudinal
      evaluation of 4 cases].
AB  - AIM: Lactating adenoma are circumscribed benign breast lesions developing during
      pregnancy or lactation due to overall enhanced proliferation of steroid hormone
      dependent tissue. Sonography is the method of choice for imaging mainly because
      of the physiologically dense breast tissue. Which is the predictive value of
      sonography in the diagnosis of lactating adenoma? Are sonographic characteristics
      dependent on age of gestation or time of lactation? Which diagnostic procedure
      should be recommended? METHOD: We report the long time course of four patients
      with histologically proven (core-needle biopsy, 16 Gauge) lactating adenoma,
      first diagnosed during pregnancy, which were followed up sonographically (1997
      2000) with real-time B-mode, panorama-mode (Siescape) and colour-sonography.
      RESULTS: Demonstrating a high inter- and intraindividual variability the tumors
      were biggest around parturitation. Despite ongoing lactation tumors regressed in
      size, but did not vanish completely even after definite termination of breast
      feeding. Evaluation of sonographical characteristics did not allow to rule out
      malignancy. CONCLUSION: Three percent of all breast cancers at childbearing age
      coincide with pregnancy and lactation, therefore, an early histologic diagnosis
      is absolutely necessary. Sonographically guided core-needle biopsies allow to
      exclude malignancy without negative effects on breast feeding.

PMID- 11524698
TI  - [Sonography in hereditary angioedema: typical findings demonstrated by the
      example of 3 cases].
AB  - Hereditary angioedema (HAE) is a hereditary disorder (deficiency of C1 esterase
      inhibitor) with spontaneous cutaneous and subcutaneous edemas, which involve the
      gastrointestinal tract in 50 - 75 %. Recurrent abdominal pain attacks in younger
      patients with an ultrasonographic evidence of aszites (up to 1 - 2 litres are
      frequent), should always let think of a HAE. Additionally in one female patient
      we found pleural effusion repeatedly during the episodes. HAE typically shows
      segments of GI-tract with a marked wall thickening. In our patients stomach (2
      x), small bowel (2 x) and colon (1 x) were involved. Obstruction of the lumen by
      the edema may cause vomiting or ileus. By means of high-resolution sonography we
      could show for the first time that only mucosal and submucosal layer were
      affected, the L. muscularis propria was preserved. Characteristic was a
      hypoechoic thickening of the interior layers of the wall: In one patient we found
      anechoic lacunae within the mucosal layer, probably corresponding to a bullous
      edema. An accurate ultrasonic examination enables a reliable judgement of the
      severity level of HAE. It can contribute in this way to the decision whether the
      application of C1-INH-concentrate is necessary or not.

PMID- 11524697
TI  - [Ultrasonography of the Osgood-Schlatter disease].
AB  - AIM: The aim of our study was to asses the value of ultrasound in the diagnosis
      of M. Osgood-Schlatter. The results of the primary ultrasound examination were
      compared with the use of X-ray. METHOD: 15 patients were included in our study
      (average age 11 - 17 years, 8 female, 7male). All patients get an X-ray of the
      knee in two or three images. There was a reference-group of 10 patients with 20
      joints (average age 11 - 14 years). RESULTS: We observed typical sonographic
      images in different stages of M. Osgood-Schlatter. The changes depended on the
      duration of the disease. In every case we found a thickness of the patellar
      tendon of more than 1 mm (stage I and II), a bursitis infrapatellaris (stage II)
      and a fragmentation of the cortical bone of the apophysis (stage II). In cases of
      stage III disease a thickness of the patellar tendon of less than 1 mm was to be
      seen. In healthy people the average thickness of the patella tendon was 4.8 mm
      (3.5 - 5.7 mm). The maximal difference between the left and the right side was
      0.4 mm. CONCLUSIONS: With the use ultrasound in cases of M. Osgood-Schlatter a
      reduced exposure of children to X-ray is possible. Ultrasound examination is a
      clear and easy way to diagnose the disease correctly and evaluate its course and
      cure.

PMID- 11524699
TI  - [Sonographic patterns of littoral cell angioma: case report and review of the
      literature].
AB  - AIM: Littoral cell angioma is a rare benign tumour of vascular proliferation
      unique to the spleen. Definitive sonographic patterns are yet unknown and are
      described in this paper. METHOD: We report about 2 patients with histologically
      confirmed Littoral cell angioma. The sonographic features of these and 5
      additional cases in the literature are presented. RESULTS: Littoral cell angioma
      is characterized by splenomegaly (6 out of 7 cases) with small nodular
      hyperechoic focal lesions (6 out of 7 cases). A solitary hyperechoic tumour (1
      out of 7 cases) is a rare event. CONCLUSION: Littoral cell angioma is a recently
      discovered tumour and should be included in the differential diagnosis of a
      hyperechoic splenic tumour.

PMID- 11524700
TI  - [Aneurysm of the popliteal vein].
AB  - Venous aneurysms are a rare pathology. The possible complications are rupture,
      thrombosis and subsequently pulmonary embolism. The case of a 54-year-old male is
      reported, who was admitted on the suspicion of pulmonary embolism to our
      department. This suspicion was confirmed by scintigraphy and computed tomography.
      Further examination by colour coded duplex sonography showed an aneurysm of the
      popliteal vein in clinically asymptomatic legs, as a possible cause of the
      pulmonary embolism. The finding was confirmed phlebographically. After successful
      surgical treatment of the aneurysm the patient got an anticoagulation therapy for
      6 months. In the case of thromboembolism the entire venous system can be
      affected. Therefore an examination of the peripheral veins should be carried out
      whenever there is an occurrence of pulmonary embolism.

PMID- 11524701
TI  - The frequency of hereditary defective mismatch repair in a prospective series of
      unselected colorectal carcinomas.
AB  - A comprehensive analysis of somatic and germline mutations related to DNA
      mismatch-repair (MMR) genes can clarify the prevalence and mechanism of
      inactivation in colorectal carcinoma (CRC). In the present study, 257 unselected
      patients referred for CRC resection were examined for evidence of defective DNA
      MMR. In particular, we sought to determine the frequency of hereditary defects in
      DNA MMR in this cohort of patients. MMR status was assessed by testing of tumors
      for the presence or absence of hMLH1, hMSH2, and hMSH6 protein expression and for
      microsatellite instability (MSI). Of the 257 patients, 51 (20%) had evidence of
      defective MMR, demonstrating high levels of MSI (MSI-H) and an absence of either
      hMLH1 (n=48) or hMSH2 (n=3). All three patients lacking hMSH2, as well as one
      patient lacking hMLH1, also demonstrated an absence of hMSH6. DNA sequence
      analysis of the 51 patients with defective MMR revealed seven germline mutations
      four in hMLH1 (two truncating and two missense) and three in hMSH2 (all
      truncating). A detailed family history was available for 225 of the 257 patients.
      Of the seven patients with germline mutations, only three had family histories
      consistent with hereditary nonpolyposis colorectal cancer. Of the remaining
      patients who had tumors with defective MMR, eight had somatic mutations in hMLH1.
      In addition, hypermethylation of the hMLH1 gene promoter was present in 37 (88%)
      of the 42 hMLH1-negative cases available for study and in all MSI-H tumors that
      showed loss of hMLH1 expression but no detectable hMLH1 mutations. Our results
      suggest that, although defective DNA MMR occurs in approximately 20% of
      unselected patients presenting for CRC resection, hereditary CRC due to mutations
      in the MMR pathway account for only a small proportion of patients. Of the 257
      patients, only 5 (1.9%) appear to have unequivocal evidence of hereditary defects
      in MMR. The epigenetic (nonhereditary) mechanism of hMLH1 promoter
      hypermethylation appears to be responsible for the majority of the remaining
      patients whose tumors are characterized by defective DNA MMR.

PMID- 11524704
TI  - Maximizing antimicrobial efficacy, minimizing antimicrobial resistance: a
      paradigm for the new millennium. Proceedings of a symposium. Cambridge,
      Massachusetts, USA. 7-8 December 1999.

PMID- 11524702
TI  - Mutations in a novel gene with transmembrane domains underlie Usher syndrome type
      3.
AB  - Usher syndrome type 3 (USH3) is an autosomal recessive disorder characterized by
      progressive hearing loss, severe retinal degeneration, and variably present
      vestibular dysfunction, assigned to 3q21-q25. Here, we report on the positional
      cloning of the USH3 gene. By haplotype and linkage-disequilibrium analyses in
      Finnish carriers of a putative founder mutation, the critical region was narrowed
      to 250 kb, of which we sequenced, assembled, and annotated 207 kb. Two novel
      genes-NOPAR and UCRP-and one previously identified gene-H963-were excluded as
      USH3, on the basis of mutational analysis. USH3, the candidate gene that we
      identified, encodes a 120-amino-acid protein. Fifty-two Finnish patients were
      homozygous for a termination mutation, Y100X; patients in two Finnish families
      were compound heterozygous for Y100X and for a missense mutation, M44K, whereas
      patients in an Italian family were homozygous for a 3-bp deletion leading to an
      amino acid deletion and substitution. USH3 has two predicted transmembrane
      domains, and it shows no homology to known genes. As revealed by northern
      blotting and reverse-transcriptase PCR, it is expressed in many tissues,
      including the retina.

PMID- 11524703
TI  - A recessive contiguous gene deletion of chromosome 2p16 associated with
      cystinuria and a mitochondrial disease.
AB  - Deletions ranging from 100 Kb to 1 Mb--too small to be detected under the
      microscope--may still involve dozens of genes, thus causing microdeletion
      syndromes. The vast majority of these syndromes are caused by haploinsufficiency
      of one or several genes and are transmitted as dominant traits. We identified
      seven patients originating from an extended family and presenting with a unique
      syndrome, inherited in a recessive mode, consisting of cystinuria, neonatal
      seizures, hypotonia, severe somatic and developmental delay, facial dysmorphism,
      and lactic acidemia. Reduced activity of all the respiratory chain enzymatic
      complexes that are encoded in the mitochondria was found in muscle biopsy
      specimens of the patients examined. The molecular basis of this disorder is a
      homozygous deletion of 179,311 bp on chromosome 2p16, which includes the type I
      cystinuria gene (SLC3A1), the protein phosphatase 2Cbeta gene (PP2Cbeta), an
      unidentified gene (KIAA0436), and several expressed sequence tags. The extent of
      the deletion suggests that this unique syndrome is related to the complete
      absence of these genes' products, one of which may be essential for the synthesis
      of mitochondrial encoded proteins.

PMID- 11524705
TI  - Development and spread of bacterial resistance to antimicrobial agents: an
      overview.
AB  - Resistance to antimicrobial agents is emerging in a wide variety of nosocomial
      and community-acquired pathogens. The emergence and spread of multiply resistant
      organisms represent the convergence of a variety of factors that include
      mutations in common resistance genes that extend their spectrum of activity, the
      exchange of genetic information among microorganisms, the evolution of selective
      pressures in hospitals and communities that facilitate the development and spread
      of resistant organisms, the proliferation and spread of multiply resistant clones
      of bacteria, and the inability of some laboratory testing methods to detect
      emerging resistance phenotypes. Twenty years ago, bacteria that were resistant to
      antimicrobial agents were easy to detect in the laboratory because the
      concentration of drug required to inhibit their growth was usually quite high and
      distinctly different from that of susceptible strains. Newer mechanisms of
      resistance, however, often result in much more subtle shifts in bacterial
      population distributions. Perhaps the most difficult phenotypes to detect, as
      shown in several proficiency testing surveys, are decreased susceptibility to
      beta-lactams in pneumococci and decreased susceptibility to vancomycin in
      staphylococci. In summary, emerging resistance has required adaptations and
      modifications of laboratory diagnostic techniques, empiric anti-infective therapy
      for such diseases as bacterial meningitis, and infection control measures in
      health care facilities of all kinds. Judicious use is imperative if we are to
      preserve our arsenal of antimicrobial agents into the next decade.

PMID- 11524706
TI  - Globalization of antimicrobial resistance: epidemiological challenges.
AB  - Globalization of antimicrobial resistance is a reality, but before the relative
      impact of global versus local spread of resistant microorganisms can be
      quantified, surveillance capacity and information transfer must be greatly
      enhanced.

PMID- 11524707
TI  - Using internet discussion of antimicrobial susceptibility databases for
      continuous quality improvement of the testing and management of antimicrobial
      resistance.
AB  - Accurate results from the world's microbiology laboratories are essential for
      care of patients, control of hospital and community infections, and global
      epidemiology. Yet those laboratories differ greatly in their access to supplies,
      published literature and standards, training courses, peer interaction, and
      mandated quality control. Because much of what is needed is information, new
      information technology should help. In particular, measurements of susceptibility
      to antimicrobial agents, now increasingly filed in electronic databases, exhibit
      many kinds of variances due both to test performance and to the diversity of
      bacteria and of their mechanisms of resistance. In industry, workers' ongoing
      evaluation of variances in measurements of performance has been the basis of
      management programs of continuous quality improvement. Examples suggest how
      collegial evaluation of variances in shared susceptibility test data might
      similarly improve quality not only of testing but also of other aspects of the
      management of antimicrobial resistance. Internet access is now making such
      ongoing evaluation and discussion increasingly possible in most parts of the
      world.

PMID- 11524708
TI  - Antibiotic resistance: consequences of inaction.
AB  - Bacterial resistance presents therapeutic dilemmas to clinicians worldwide. The
      warnings were there long ago, but too few people heeded them. Thus an emerging
      problem has grown to a crisis. Resistance is an ecological phenomenon stemming
      from the response of bacteria to the widespread use of antibiotics and their
      presence in the environment. While determining the consequences of inaction on
      the present and future public health, we must work to remedy the lack of action
      in the past. By improving antibiotic use and decreasing resistance gene frequency
      at the local levels, we can move towards reversing the resistance problem
      globally.

PMID- 11524709
TI  - Prudent use of antibiotics: are our expectations justified?
AB  - Prudent use of antibiotics has 3 components, rational use, adherence to local
      guidelines and policies, and avoidance or reversal of upward demographic trends
      in antibiotic resistance. Although rational use is mandatory, it must be
      recognized that adherence to policies will reduce clinical freedom, for good or
      ill. Expectations that prudent use will deliver reversals in resistance trends
      should be accepted with caution. Sound, pertinent data are lacking, and our
      ability to detect change, if it does occur, and to attribute its cause correctly,
      is questionable.

PMID- 11524710
TI  - Consequences of inaction: importance of infection control practices.
AB  - The increasing prevalence of antimicrobial-resistant pathogens in health care
      facilities is due in large part to overuse of antibiotics and poor compliance
      with recommended infection control practices. To control the spread of such
      pathogens, health care facilities must reduce overuse and abuse of antibiotics,
      and they must implement new multidisciplinary programs to improve hand hygiene
      practices among health care workers and improve compliance with recommended
      barrier precautions.

PMID- 11524711
TI  - Minimizing potential resistance: the molecular view.
AB  - The major contribution of molecular biology to the study of antibiotic resistance
      has been the elucidation of nearly all biochemical mechanisms of resistance and
      the routes for dissemination of genetic information among bacteria. In this
      review, we consider the potential contribution of molecular biology to
      counteracting the evolution of resistant bacteria. In particular, we emphasize
      the fact that fundamental approaches have had direct practical effects on
      minimizing potential resistance: by improving interpretation of resistance
      phenotypes, by providing more adequate human therapy, by fostering more prudent
      use of antibiotics, and by allowing the rational design of new drugs that evade
      existing resistance mechanisms or address unexploited targets.

PMID- 11524712
TI  - Restricting the selection of antibiotic-resistant mutants: a general strategy
      derived from fluoroquinolone studies.
AB  - Studies with fluoroquinolones have led to a general method for restricting the
      selection of antibiotic-resistant mutants. The strategy is based on the use of
      antibiotic concentrations that require cells to obtain 2 concurrent resistance
      mutations for growth. That concentration has been called the "mutant prevention
      concentration" (MPC) because no resistant colony is recovered even when >10(10)
      cells are plated. Resistant mutants are selected exclusively within a
      concentration range (mutant selection window) that extends from the point where
      growth inhibition begins, approximated by the minimal inhibitory concentration,
      up to the MPC. The dimensions of the mutant selection window can be reduced in a
      variety of ways, including adjustment of antibiotic structure and dosage
      regimens. The window can be closed to prevent mutant selection through
      combination therapy with > or =2 antimicrobial agents if their normalized
      pharmacokinetic profiles superimpose at concentrations that inhibit growth.
      Application of these principles could drastically restrict the selection of drug
      resistant pathogens.

PMID- 11524713
TI  - Minimizing potential resistance: the molecular view--a comment on Courvalin and
      Trieu-Cuot.
AB  - The complexity of bacterial resistance to antimicrobial agents is driven by the
      interplay of many mechanistic and epidemiologic factors. Mechanistically,
      resistance by target alteration, reduced permeation, and drug inactivation can
      occur by both chromosomal mutation and acquisition of new genetic elements.
      Epidemiologically, exposure to antimicrobial agents provides a growth or
      persistence advantage for any existing resistant bacteria, generally irrespective
      of the mechanism. When a single chromosomal mutation is sufficient to cause
      resistance, any such exposure provides a risk of selection, as long as a
      sufficiently large bacterial population is exposed. Transmission of resistant
      bacteria can also amplify resistance of any type, but it is particularly
      important for complex resistance mechanisms that have evolved over time and for
      mechanisms that depend on infrequent biological events in nature. Because true
      biological barriers to the development of resistance are likely to be elusive,
      multiple approaches that address both the use of antimicrobial agents and
      transmission are necessary to slow the advance of resistance.

PMID- 11524714
TI  - Minimizing potential resistance: a population dynamics view.
AB  - I examine the results of studies that used mathematical models of the
      epidemiology and population genetics of antibiotic treatment and resistance in
      open communities and in hospitals to explore the following issues: the
      relationship between antibiotic consumption and the frequency of antibiotic
      resistance in bacterial populations in communities and in hospitals; methods of
      controlling the growth, dissemination, and persistence of antibiotic resistance
      in these settings; the extent to which resistance can be controlled; and the
      speed with which the effects of control measures will be realized. In open
      communities, it will take years or even decades to see substantial reductions in
      the frequency of antibiotic resistance solely as a result of more prudent
      (reduced) use of antibiotics. However, if we can restrict the input of resistant
      bacteria into hospitals, through the application of infection control and other
      measures, it should be possible to reduce the frequency of resistance and even
      eliminate resistant bacteria from these institutions in short order.

PMID- 11524715
TI  - Patients' interviews and misuse of antibiotics.
AB  - To better evaluate patient contribution in antibiotic use, we questioned 5379
      subjects from 9 countries. Antibiotics are perceived as strong, efficient drugs,
      but they are believed to undermine immunity. Interviewees believe that most
      respiratory infections, except the common cold, require antibiotic therapy, and
      11% of them had to exaggerate their symptoms to get an antibiotic prescription
      from their physician. About 1 patient in 4 saved part of the antibiotic course
      for future use. Sixty-nine percent of the patients claimed to have taken the
      course until the end (United Kingdom, 90%; Thailand, 53%), and 75% claimed that
      they actually took all the daily doses. In all countries, it was possible to get
      antibiotics from a pharmacist without a medical prescription. This study shows
      that patients exert pressure on their doctors to get antibiotics and should allow
      a design for precise educational action aimed at the public for better control of
      antibiotic use in the community.

PMID- 11524716
TI  - Mathematical models as tools for evaluating the effectiveness of interventions: a
      comment on Levin.
AB  - Possible interventions to minimize resistance rates are numerous and can involve
      reduction and/or change in antimicrobial use, infection control, and
      vaccinations. As mathematical models are becoming more realistic they can be
      useful to quantitatively evaluate the relative contribution of individual risk
      factors and for the planning of future intervention strategies. The fitness cost
      associated with resistance is an important parameter and small differences can
      have a profound effect on the results. The mathematical models presented for
      communities predicted that even with cessation of antibiotic use, the decline in
      resistance frequency would be slow. This contrasts with successful interventions
      in Finland and Iceland. Future models have to include important variables such as
      herd immunity and take into account the heterogeneity of open communities.
      Provision of susceptible strains from areas with low resistance rates to areas
      with high resistance rates can have a profound effect on the success of
      interventions to minimize resistance.

PMID- 11524717
TI  - Quinolone molecular structure-activity relationships: what we have learned about
      improving antimicrobial activity.
AB  - Recently, understanding of how molecular modifications of the core quinolone
      structure affect(s) antimicrobial agent activity has progressed rapidly. Three
      positions (2, 3, and 4) cannot be changed without a significant loss of
      biological activity. Furthermore, it appears that a cyclopropyl group is optimal
      at position 1. Substituents at positions 5 and 8 affect planar configuration, and
      either a methyl or methoxy appear optimal at these sites. Hydrogen and amino
      groups have been investigated as useful substituents at position 6, replacing the
      fluorine of the fluoroquinolones. Interestingly, in vitro activity enhancement
      observed with alterations at positions 5 and 6 is not always accompanied by
      improved in vivo action. For all these modifications, the substituents at
      positions 7 and 8 are critical for potent antimicrobial activity. Optimizing
      overall molecular configuration enhances the number of intracellular targets for
      antimicrobial action (R-8) and impedes the efficiency of efflux proteins (R-7)
      that diminish intracellular penetration.

PMID- 11524718
TI  - Antimicrobial use and the emergence of antimicrobial resistance with
      Streptococcus pneumoniae in the United States.
AB  - The rapid emergence of resistance to antimicrobial agents by Streptococcus
      pneumoniae in the United States has been influenced by various factors, including
      the clonal nature of most resistant strains and the fact that organisms with a
      multiresistant phenotype have become stably endemic. The ease with which
      transmission occurs and the fact that humans, especially children, are often
      colonized asymptomatically in the upper respiratory tract have contributed to the
      problem. Clearly, the most important factor in the emergence of antimicrobial
      resistance with S. pneumoniae, however, is the selective pressure of
      antimicrobial agents. Potency, defined as a product of both antibacterial effect
      and drug delivery, is a key factor. Generally speaking, the more potent an
      antimicrobial agent, the less likely it is to select for resistance. This is
      germane to comparisons of oral agents within specific antimicrobial classes
      (e.g., beta-lactams, macrolides, and fluoroquinolones). Within each class,
      potencies differ. In view of the existence of stably endemic multidrug-resistant
      S. pneumoniae, given comparable cost, side-effect profile, palatability,
      convenience of dosing, and accessibility, use of the most potent agent(s) within
      a particular class is advocated.

PMID- 11524719
TI  - Association between antibiotic resistance and community prescribing: a critical
      review of bias and confounding in published studies.
AB  - The reported association between antibiotic prescribing and resistance may be
      subject to bias or confounding. Bias describes any effect at any stage of
      investigation or inference tending to produce results that depart systematically
      from the true value. A confounding variable is one that is associated
      independently with both exposure and outcome. Confounding variables may create an
      apparent association or mask a real association. Pharmacoepidemiology is the
      study of the use and the effects of drugs in large numbers of people. We have
      used standard pharmacoepidemiological methods to investigate sources of bias and
      confounding in the association between prescribing and resistance. We conclude
      that the association is statistically valid and that the consistency of evidence
      supports a cause-effect relationship. Nonetheless, several important sources of
      bias and confounding must be taken into account in future studies that analyze
      the impact of prescribing policies on resistance.

PMID- 11524720
TI  - Antimicrobial drug use and resistance among respiratory pathogens in the
      community.
AB  - There is substantial evidence that the overuse of antibiotics is a major cause
      for the emergence of resistance in respiratory pathogens in the community.
      However, it is also recognized that the mechanisms of resistance, the cost of
      resistance to the fitness of the organism, and the ability of the resistant
      strain to disseminate are all important contributors to this problem. Therefore,
      when developing strategies to control and/or prevent the emergence of resistance,
      health care professionals must take each of these factors into consideration. As
      we enter a new era in the use of fluoroquinolones for the treatment of
      respiratory tract infections, we have an opportunity to apply such lessons
      learned in the past to minimize or prevent the development of resistance to this
      class of antimicrobial drugs in the future.

PMID- 11524721
TI  - In vitro models, in vivo models, and pharmacokinetics: what can we learn from in
      vitro models?
AB  - In vitro pharmacokinetic models of infection can make an important contribution
      to the study of the pharmacodynamic properties of an antibacterial agent. In
      conjunction with animal and human pharmacodynamic evaluations, they provide data
      to allow for the optimization of drug dosing regimens. In vitro models can be
      used simply to describe the effect of a drug on a bacterial population as well as
      to provide data for more-analytical studies, including hypothesis testing.
      Analytical study designs provide information on the pharmacodynamic parameter
      best related to the chosen outcome, as well as its magnitude. Factors such as the
      characteristics of the model (method of drug removal, inoculum density, and
      growth phase), doses simulated, species and susceptibility range of bacteria, and
      methods and analytical tools used to measure antibacterial effect will have an
      effect on the conclusions drawn. In vitro models have an important future role in
      ensuring antibiotic efficacy and in reducing the risks of resistance.

PMID- 11524722
TI  - Perspective on animal models: chronic intracellular infections.
AB  - Systemic human disease caused by organisms of the Mycobacterium avium
      Mycobacterium intracellulare complex (MAC) represent a chronic intracellular
      infection in human hosts who are usually immunocompromised. To develop improved
      treatment and prophylaxis, and to obtain a better understanding of pathogenesis,
      we studied the beige mouse (C57 beige(+)/beige(+)) challenged orally or
      intravenously with a human isolate that causes lethal disease in patients with
      AIDS (MAC 101, serovar 1). Encouraging anti-MAC studies in animals, as reviewed
      here, should provide the basis for considering human trials with a promising
      agent. The ability of an antimicrobial agent to achieve high intracellular
      concentrations has correlated with the in vivo activity of several specific
      compounds.

PMID- 11524723
TI  - Should we reevaluate antibiotic breakpoints?
AB  - The breakpoints used to interpret antimicrobial susceptibility tests should be
      carefully determined initially, using microbiological, pharmacokinetic,
      pharmacodynamic, and clinical data, and then reevaluated periodically as changes
      in bacterial resistance, susceptibility test methods, or antibiotic formulations
      occur. Throughout the world, different governmental agencies and professional
      organizations have responsibility for the initial establishment of antibiotic
      susceptibility breakpoints. In the United States, the National Committee for
      Clinical Laboratory Standards has a mechanism in place to establish breakpoints
      initially and to review and publish updates on an annual basis. There should be a
      continued effort to coordinate both susceptibility testing methods and breakpoint
      determinations in various parts of the world.

PMID- 11524724
TI  - Does the dose matter?
AB  - Pharmacokinetic/pharmacodynamic (PK/PD) parameters, such as the ratio of peak to
      minimum inhibitory concentration (peak/MIC ratio), ratio of 24-hour area under
      the curve to MIC (24-h AUC/MIC ratio), and the time above MIC, are good
      indicators of the drug dose-organism interaction. Time above the MIC is the
      important determinant of the activity of beta-lactams, macrolides, clindamycin,
      and linezolid. Free drug serum levels of these drugs should be above the MIC for
      at least 40%-50% of the dosing interval to produce adequate clinical and
      microbiological efficacy. Peak/MIC and 24-h AUC/MIC ratios are major determinants
      of the activity of aminoglycosides and fluoroquinolones. In general, peak/MIC
      ratios should exceed 8 and 24-h AUC/MIC values should be >100 to successfully
      treat gram-negative bacillary infections and to prevent the emergence of
      resistant organisms during therapy. The successful treatment of pneumococcal
      infections with fluoroquinolones and azithromycin appear to require 24-h AUC/MIC
      ratios of only 25-35. Mutation prevention concentrations are being reported for
      various fluoroquinolones with different pathogens, but their clinical
      significance has not yet been established. More information is needed on the role
      of PK/PD parameters and their magnitude for preventing mutations and the
      emergence of resistant organisms for most classes of antibiotics.

PMID- 11524725
TI  - Role of pharmacokinetics and pharmacodynamics: does the dose matter?
AB  - Antibiotic dose is important in determining serum area-under-the-curve (AUC) and
      peak serum concentration (C(max)), as well as the time the serum concentration
      remains over the pathogen minimum inhibitory concentration (T>MIC). However, dose
      is not the sole determinant of these factors; they are modified by absorption,
      clearance, and frequency of dosing. It is difficult to relate dose to clinical
      outcome in humans, but pharmacodynamic parameters (AUC/MIC, C(max)/MIC, or T>MIC)
      have been related to clinical and bacteriological efficacy or emergence of
      resistance to aminoglycosides, fluoroquinolones, glycopeptides, and beta-lactams.

PMID- 11524726
TI  - Can we influence prescribing patterns?
AB  - A variety of programming techniques and methods of training have been employed to
      change physician behavior. Didactic continuing medical education lectures and
      clinical guidelines have had minimal impact, although endorsement of national
      professional guidelines by local opinion leaders appears to have a positive
      influence on the impact of professional guidelines. Interactive, hands-on
      workshops, performance reporting, and peer/patient feedback are also effective.
      Changing prescribing habits has been equally difficult. Drug utilization letters
      involving both pharmacist and physician have more impact than do letters sent
      only to the physician. Academic detailing, when properly executed, has been
      consistently effective. When combined with these strategies, closed formularies
      become a powerful tool in changing prescribing behavior.

PMID- 11524727
TI  - Promoting appropriate antimicrobial drug use: perspective from the Centers for
      Disease Control and Prevention.
AB  - Extending the useful life of antimicrobial drugs through appropriate use-that is,
      use that maximizes therapeutic impact while minimizing toxicity and the
      development of resistance-is an important component of efforts to prevent and
      control the emerging threat of antimicrobial resistance. The major paradigms of
      antimicrobial drug use involve acute infections in outpatients, acute infections
      in inpatients, chronic infections, and agriculture/veterinary medicine. The
      factors that influence drug use and the challenges that need to be addressed in
      promoting more appropriate use are different in each of these paradigms. For
      acute respiratory infections in outpatients, data from intervention trials
      suggest that concurrent multifaceted interventions may be effective in promoting
      appropriate drug prescribing. The next challenge is to extend these interventions
      to larger populations by incorporating them into routine medical practice.

PMID- 11524729
TI  - Mutation analysis in mitochondrial fatty acid oxidation defects: Exemplified by
      acyl-CoA dehydrogenase deficiencies, with special focus on genotype-phenotype
      relationship.
AB  - Mutation analysis of metabolic disorders, such as the fatty acid oxidation
      defects, offers an additional, and often superior, tool for specific diagnosis
      compared to traditional enzymatic assays. With the advancement of the structural
      part of the Human Genome Project and the creation of mutation databases,
      procedures for convenient and reliable genetic analyses are being developed. The
      most straightforward application of mutation analysis is to specific diagnoses in
      suspected patients, particularly in the context of family studies and for
      prenatal/preimplantation analysis. In addition, from these practical uses emerges
      the possibility to study genotype-phenotype relationships and investigate the
      molecular pathogenesis resulting from specific mutations or groups of mutations.
      In the present review we summarize current knowledge regarding genotype-phenotype
      relationships in three disorders of mitochondrial fatty acid oxidation: very-long
      chain acyl-CoA dehydrogenase (VLCAD, also ACADVL), medium-chain acyl-CoA
      dehydrogenase (MCAD, also ACADM), and short-chain acyl-CoA dehydrogenase (SCAD,
      also ACADS) deficiencies. On the basis of this knowledge we discuss current
      understanding of the structural implications of mutation type, as well as the
      modulating effect of the mitochondrial protein quality control systems, composed
      of molecular chaperones and intracellular proteases. We propose that the
      unraveling of the genetic and cellular determinants of the modulating effects of
      protein quality control systems may help to assess the balance between genetic
      and environmental factors in the clinical expression of a given mutation. The
      realization that the effect of the monogene, such as disease-causing mutations in
      the VLCAD, MCAD, and SCAD genes, may be modified by variations in other genes
      presages the need for profile analyses of additional genetic variations. The
      rapid development of mutation detection systems, such as the chip technologies,
      makes such profile analyses feasible. However, it remains to be seen to what
      extent mutation analysis will be used for diagnosis of fatty acid oxidation
      defects and other metabolic disorders.

PMID- 11524730
TI  - RNase cleavage-based methods for mutation/SNP detection, past and present.
AB  - Mutation detection based on ribonuclease cleavage of basepair mismatches in
      single-stranded RNA probes hybridized to DNA targets was first described over 15
      years ago. The original methods relied on RNase A for mismatch cleavage; however,
      this enzyme fails to cleave many mismatches and has other drawbacks. More
      recently, a new method for RNase-cleavage-based mutation scanning has been
      developed, which takes advantage of the ability of RNase 1 and RNase T1 to cleave
      mismatches in duplex RNA targets, when these enzymes are used in conjunction with
      nucleic acid intercalating dyes. The method, called NIRCA, is relatively low-cost
      in terms of materials and equipment required. It is being used to detect
      mutations and SNPs in a wide variety of genes involved in human genetic disease
      and cancer, as well as in disease-related viral and bacterial genes. This review
      describes historical and recently developed RNase cleavage-based methods for
      mutation/SNP scanning.

PMID- 11524731
TI  - APECED mutations in the autoimmune regulator (AIRE) gene.
AB  - Autoimmune polyendocrinopathy candidiasis-ectodermal dystrophy (APECED) is a rare
      recessively inherited disorder caused by mutations in the AIRE (autoimmune
      regulator) gene. APECED is characterized by variable combinations of endocrine
      autoimmune diseases such as Addison's disease, hypoparathyroidism, and type 1
      diabetes. The AIRE protein contains motifs suggestive of a transcription
      regulator and can activate transcription of a reporter gene when fused to a
      heterologous DNA biding domain. In this article, mutation analyses of over 200
      APECED patients published by several laboratories are summarized. To date 42
      different mutations have been identified. These mutations include nonsense and
      missense mutations, small insertions and deletions leading into frame shifts, and
      splice site mutations. Although mutations are spread throughout the coding region
      of the gene some hotspots emerge, including the more common and recurrent
      mutations R257X and 967-979del13bp. Some of the identified mutations have been
      shown to affect subcellular localization or transactivation properties of the
      protein, thus providing insights into the functional properties of the predicted
      protein motifs.

PMID- 11524733
TI  - Novel AIRE mutations and P450 cytochrome autoantibodies in Central and Eastern
      European patients with APECED.
AB  - Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare
      recessive disorder that results in several autoimmune diseases due to the
      mutations in the AIRE (autoimmune regulator) gene. APECED patients develop
      several autoimmune endocrine disorders and are characterized by the high titer
      autoantibodies to organ-specific antigens such as the steroidogenic P450
      cytochromes. So far, 38 mutations have been identified in the AIRE gene. We
      report here the genetic and autoantibody analysis of 27 APECED patients of
      Eastern and Central European origins and one Egyptian patient. From 54 analyzed
      APECED chromosomes, eight mutations were detected, four of which (T16M, W78R,
      IVS1_IVS4, 30-53dup23bp) are novel. The most prevalent reason for APECED in these
      populations was the occurrence of R257X (36 chromosomes) that has been described
      earlier as a common and recurrent mutation in several other populations. The
      analysis of humoral immunity to steroidogenic P450 cytochromes by the
      immunoblotting of E. coli expressed antigens in the 18 APECED patients showed
      that 67%, 44%, and 61% of the Eastern and Central European APECED patients had
      autoantibodies to P450c17, P450c21, and P450scc, respectively.

PMID- 11524732
TI  - High incidence of N and K-Ras activating mutations in multiple myeloma and
      primary plasma cell leukemia at diagnosis.
AB  - Using allele-specific amplification method (ARMS), a highly sensitive one-stage
      allele-specific PCR, we have evaluated the incidence of NRAS and KRAS2 activating
      mutations (codons 12, 13, and 61) in 62 patients with either monoclonal
      gammopathy of undetermined significance (MGUS) or multiple myeloma (MM), primary
      plasma-cell leukemia (P-PCL), and also in human myeloma cell lines (HMCL). NRAS
      and/or KRAS2 mutations were found in 54.5% of MM at diagnosis (but in 81% at the
      time of relapse), in 50% of P-PCL, and in 50% of 16 HMCL. In contrast, the
      occurrence of such mutations was very low in MGUS and indolent MM (12.50%). Of
      note, KRAS2 mutations were always more frequent than NRAS. The validity of the
      technique was assessed by direct sequencing of cell lines and of some patients.
      Multiple mutations found in two patients were confirmed by subcloning exon PCR
      amplification products, testing clones with our method, and sequencing them.
      Thus, these early mutations could play a major role in the oncogenesis of MM and
      P-PCL.

PMID- 11524735
TI  - Mutation detection in the alpha-1 antitrypsin gene (PI) using denaturing gradient
      gel electrophoresis.
AB  - A method for mutation detection in the alpha-1 antitrypsin gene (protease
      inhibitor 1; PI) has been developed using denaturing gradient gel electrophoresis
      of PCR amplified gene fragments. Using this experimental approach, all common
      phenotypes and mutations could be detected. Denaturing gradient gel
      electrophoresis (DGGE) was compared with standard isoelectric focusing (IEF) in
      20 potential alpha1-antitrypsin deficient patients and their relatives. The
      genotype determined by DGGE was found to be more reliable in some cases than IEF,
      which is essential for a proper diagnosis of alpha-1 antitrypsin malfunctioning.

PMID- 11524736
TI  - Detection of six novel FBN1 mutations in British patients affected by Marfan
      syndrome.
AB  - Marfan syndrome (MFS), an autosomal dominant disorder of the extracellular
      matrix, is due to mutations in fibrillin-1 (FBN1) gene. Investigations carried
      out in the last decade, unveiled the unpredictability of the site of the
      mutation, which could be anywhere in the gene. FBN1 mutations have been reported
      in a spectrum of diseases related to MFS, with no clear evidence for a phenotype
      genotype correlation. In this paper we analysed 10 British patients affected by
      MFS and we were able to characterise five novel missense mutations (C474W,
      C1402Y, G1987R, C2153Y, G2536R), one novel frameshift mutation (7926delC), one
      already described mutation (P1424A) and one FBN1 variant (P1148A) classified as a
      polymorphism in the Asian population. Four out of the five novel missense
      mutations involved either cysteines or an amino acid conserved in the domain
      structure. The mutation yield in this study is calculated at 80.0% (8/10), thus
      indicating that SSCA is a reliable and cost-effective technique for the screening
      of such a large gene. Our results suggest that this method is reliable to search
      for FBN1 mutations and that FBN1 screening could be a helpful tool to confirm and
      possibly anticipate the clinical diagnosis in familial cases. Hum Mutat 18:251,
      2001.

PMID- 11524734
TI  - Identification of seven novel mutations including the first two genomic
      rearrangements in SLC26A3 mutated in congenital chloride diarrhea.
AB  - Congenital chloride diarrhea (CLD) is an autosomal recessive disorder
      characterized by defective intestinal electrolyte absorption, resulting in
      voluminous osmotic diarrhea with high chloride content. A variety of mutations in
      the solute carrier family 26, member 3 gene (SLC26A3, previously known as CLD or
      DRA) are responsible for the disease. Since the identification of the SLC26A3
      gene and the determination of its genomic structure, altogether three founder and
      17 private mutations have been characterized within miscellaneous ethnic groups.
      We screened for mutations in seven unrelated families with CLD. The diagnoses
      were confirmed by fecal chloride measurements. The combined PCR-SSCP and
      sequencing analyses revealed altogether seven novel mutations including two
      missense mutations (S206P, D468V), two splicing defects (IVS12-1G>C, IVS13
      2delA), one nonsense mutation (Q436X), one insertion/deletion mutation (2104
      2105delGGins29-bp), and an intragenic deletion of SLC26A3 exons 7 and 8. Two
      previously identified mutations were also found. This is the first report of
      rearrangement mutations in SLC26A3. Molecular features predisposing SLC26A3 for
      the two rearrangements may include repetitive elements and palindromic-like
      sequences. The increasingly wide diversity of SLC26A3 mutations suggests that
      mutations in the SLC26A3 gene may not be rare events.

PMID- 11524739
TI  - Identification of four novel RB1 germline mutations in Korean retinoblastoma
      patients.
AB  - To elucidate RB1 germline mutations in Korean retinoblastoma patients, DNA
      samples from 14 children with bilateral (including three familial cases) and 19
      children with unilateral retinoblastoma were analyzed. We found germline
      mutations in three out of 14 bilateral cases and one out of 19 unilateral cases.
      There were no germline mutations in the three familial cases. PCR-SSCP from each
      exon showed bandshifts in four patients which, upon sequencing, were shown to be
      K616E in exon 19 (c.1846A>G), an AA insertion in exon 7 (c.684-685insAA), R500G
      in exon 16 (c.1498A>G), and an A insertion in exon 23 (c.2391-2392insA),
      respectively. Hum Mutat 18:252, 2001.

PMID- 11524737
TI  - Five novel frameshift mutations in exon 3 and 4 of the MECP2 gene identified in
      Rett patients: Consequences for the molecular diagnosis strategy.
AB  - Rett syndrome (RTT) is a severe progressive neurological disorder that affects
      almost exclusively females. The gene responsible for this disorder, MECP2, was
      recently identified by candidate gene strategy. Mutations were detected in 70-85%
      of RTT cases. We report here five novel frameshift mutations (named 345delC,
      895del202, 989ins18del8, 996insAG and 1124del53) in exon 3 and 4 of the MECP2
      gene. To avoid the missing of few small deletions in RTT patients using classical
      mutation screening approaches, we suggest that screening of the mutations in the
      MECP2 gene in RTT girls should include at least a large PCR to amplify exon 4
      entirely.

PMID- 11524738
TI  - Molecular basis of phenylketonuria in Cuba.
AB  - In this study we report the mutation analysis performed in Cuban PKU patients
      using DGGE and direct sequencing. Sixteen different mutations have been detected,
      which account for 91% of the total mutant alleles. Haplotype analysis and
      genealogical data support the European (mainly Spanish) origin of the mutations.
      Two mutations were found at unexpectedly high frequencies, E280K and R261Q,
      possibly due to consanguinity and genetic drift, among other factors. Hum Mutat
      18:252, 2001.

PMID- 11524740
TI  - Spectrum of low density lipoprotein receptor mutations in Czech
      hypercholesterolemic patients.
AB  - The aim of our study was to define mutations causing familial
      hypercholesterolemia (FH) phenotype in Czech hypercholesterolemic individuals. A
      combination of heteroduplex analysis, SSCP, DGGE, DNA sequencing and
      PCR/restriction analysis was used for this purpose. Molecular searching in the
      promoter region and coding sequence of the low density lipoprotein receptor
      (LDLR) gene in 130 patients from 68 unrelated families resulted in the
      identification of 37 sequence variations. Thirty of them are most likely disease
      causing mutations. Nineteen mutations were novel (two nonsense, five missense,
      six nucleotide(s) insertions and six nucleotide(s) deletions). Their pathological
      effect can be predicted on the basis of their position with respect to previously
      reported mutations with an estimated reduction of the receptor activity and/or
      premature termination of translation. These results expand our knowledge of
      mutations responsible for FH. Seven nucleotide variations were characterized as
      silent polymorphisms. Hum Mutat 18:253, 2001.

PMID- 11524742
TI  - A novel in-frame deletion mutation (c106-111del) identified in a Taiwan Chinese
      patient with type IVA mucopolysaccharidosis.

PMID- 11524743
TI  - [Influenza pandemic was probably avoided with effort and luck--thus far].

PMID- 11524741
TI  - Molecular analysis of Japanese patients with Rett syndrome: Identification of
      five novel mutations and genotype-phenotype correlation.
AB  - Rett syndrome is an X-linked dominant neurodevelopmental disorder that affects
      females almost exclusively. The recent identification of mutations of the methyl
      CpG-binding protein 2 gene (MECP2) in patients with RTT, encouraged us to analyze
      the gene in 37 Japanese patients divided into classical RTT (14 cases), variant
      RTT (13 cases), and mentally retarded patients with Rett-like features (10
      cases). Mutations in MECP2 were identified from most of the patients with
      classical and variant RTT (25 of 27 cases). Six reported common mutations were
      detected in 17 cases, and rare single nucleotide substitutions were found in 3
      patients. In addition, one insertion mutation (1189insA) and four deletion
      mutations including one double deletion mutant (451delG, 100del4, 1124del53 and
      881del289 plus 1187del8) were newly identified. In the 10 mentally retarded
      patients with Rett-like features, however, no mutation was detected in the coding
      region of MECP2. The finding of MECP2 mutations in 92.5% of patients with RTT
      indicates that RTT fulfilling the diagnostic criteria are due to genetic
      alteration.

PMID- 11524744
TI  - [Sources for antibacterial drugs are not drying up].

PMID- 11524745
TI  - [Effectiveness of psychosocial interventions in adolescence depressive disorder].

PMID- 11524746
TI  - [Oral lichen ruber planus--a poorly recognized illness?].

PMID- 11524747
TI  - [Sinus thrombosis in a young woman using oral contraceptives].

PMID- 11524748
TI  - [Acute hydrocephalus caused by cerebellar infarction and its treatment].

PMID- 11524749
TI  - [When the liver causes trouble].

PMID- 11524750
TI  - [A serine/threonine kinase gene defective in Peutz-Jeghers syndrome].

PMID- 11524751
TI  - [Diploma in medicine--the beginning for medical studies, not the end].

PMID- 11524752
TI  - [Initiating young doctors into the physician's work].

PMID- 11524753
TI  - [Is everything in its place in medical education?].

PMID- 11524754
TI  - [The basic medical education from the student's viewpoint].

PMID- 11524755
TI  - [The pre-clinical phase--how students have experienced their studies and the
      learning atmosphere].

PMID- 11524756
TI  - [Learning theories--a support or a burden for those who develop the education?].

PMID- 11524757
TI  - [A medical student as a researcher--how many, why and how?].

PMID- 11524758
TI  - [Difficulties when beginning in a new job--a young physician's viewpoint].

PMID- 11524759
TI  - [Does post-graduate medical training exist in Finland?].

PMID- 11524760
TI  - [The wild development of hematology].

PMID- 11524761
TI  - [Would you like to become a volunteer donor for bone marrow transplant?].

PMID- 11524762
TI  - [Thrombocyte and stem cell growth factors entering the clinics].

PMID- 11524763
TI  - [Peripheral blood smear preparation].

PMID- 11524764
TI  - [Diagnostics and treatment of iron-deficiency anemia].

PMID- 11524765
TI  - [Leukopenia investigations].

PMID- 11524766
TI  - [Diagnostics and treatment of thrombocytopenia].

PMID- 11524767
TI  - [On hematology in an immigrant].

PMID- 11524768
TI  - [Acute hematology].

PMID- 11524769
TI  - [Special features of blood transfusions to hematologic patients].

PMID- 11524771
TI  - [Indications for high-dose therapy and stem cell transplantations].

PMID- 11524770
TI  - [Interferons in the treatment of hematological diseases].

PMID- 11524772
TI  - [REAL--why again a new classification system for lymphomas?].

PMID- 11524773
TI  - [Cell therapy].

PMID- 11524774
TI  - [Gene therapy of malignant hematologic diseases].

PMID- 11524776
TI  - [The use of imaging techniques in drug research].

PMID- 11524775
TI  - [Drug addiction and withdrawal].

PMID- 11524777
TI  - [Alcohol--mechanism of action, interactions and treatment of alcohol abuse].

PMID- 11524778
TI  - [Problematic drug interactions].

PMID- 11524779
TI  - [Food and drugs].

PMID- 11524780
TI  - [Milestones of pharmacology and the outlook for drug therapy].

PMID- 11524781
TI  - [For what purposes is clinical pharmacology needed?].

PMID- 11524782
TI  - [How effective are drugs?--controlled drug trials are needed].

PMID- 11524783
TI  - [Drug research and its international harmonization].

PMID- 11524784
TI  - [Drug development--from receptor research to therapy].

PMID- 11524785
TI  - [What do we know about the drug metabolism?].

PMID- 11524786
TI  - [Analgesics and their new mechanisms of actions].

PMID- 11524787
TI  - [What's new in neuropharmacology?].

PMID- 11524788
TI  - [Treatment of acute otitis media under discussion].

PMID- 11524789
TI  - [Is susceptibility to infections in the genes?].

PMID- 11524790
TI  - [Kidney diseases and pregnancy].

PMID- 11524791
TI  - [Structural and functional brain imaging findings in obsessive-compulsive
      disorder].

PMID- 11524793
TI  - [Epidemiological relationship between owen-baked Baltic herring, homebrewed beer
      and gastroenteritis].

PMID- 11524792
TI  - [Importance of uterus and sperm glycodelins in the regulation of reproduction].

PMID- 11524794
TI  - [An unexplained cancer disease and bone metastases].

PMID- 11524795
TI  - [Vertigo accompanied with tension neck].

PMID- 11524796
TI  - [Acute otitis media in a child].

PMID- 11524797
TI  - [The mystery of hyponatremia].

PMID- 11524798
TI  - [Severity of hand joint destruction during 20 years of rheumatoid arthritis].

PMID- 11524799
TI  - [Quantitative assessment of blood flow, blood volume and blood oxygenation
      effects in functional magnetic resonance imaging].

PMID- 11524800
TI  - [How many heart beats during lifetime?].

PMID- 11524801
TI  - [The dangers of valproate in women].

PMID- 11524802
TI  - [DNA chips--a new diagnostic revolution?].

PMID- 11524803
TI  - [Analgesics and kidney].

PMID- 11524804
TI  - [In vitro methods and safety testing of chemicals].

PMID- 11524805
TI  - [Prolapsed vagina after hysterectomy--treatment methods and their effectiveness].

PMID- 11524807
TI  - [Disorders of oral motor coordination and substitute communication methods in
      "locked-in" syndrome].

PMID- 11524806
TI  - [Growth hormone therapy is useful even for adults].

PMID- 11524808
TI  - [Thrombolytic therapy of basilar artery occlusion].

PMID- 11524809
TI  - ["Girl" 46,XY].

PMID- 11524810
TI  - [Current treatment of asthma].

PMID- 11524811
TI  - [What is a proper name for Mr. Noirtier's stroke?].

PMID- 11524812
TI  - [Did Gasparo Aselli write in English?].

PMID- 11524813
TI  - [Alkaptonuria-ochronosis, the first case].

PMID- 11524814
TI  - [Once more about alkaptonuria].

PMID- 11524815
TI  - [Simple method of stereotactic radiotherapy without stereotactic body frame for
      extracranial tumors].
AB  - Thirty-five patients with metastatic lung cancer(46 lesions) and twenty patients
      with primary lung cancer (21 lesions) have been treated with a simple method of
      stereotactic radiotherapy (SRT) without stereotactic body frame. Tumor size
      ranged from 1-4 cm in diameter. We used Vac-Lok cushion(Med-Tek) as a
      immobilization system. To be sure to include the respiratory movement of tumor to
      planning target volume(PTV), every patients were examined by fluoroscopy and
      radio-opaque catheters with the same length of tumor movement were attached on
      the anterior and lateral chest wall before CT simulation. A gold grain was
      implanted into a tumor that was invisible on fluoroscopy, as a radiomaker.
      Protocol of 60 Gy/8 fractions/2 weeks and 45 Gy/3 fractions/3-6 days were mainly
      used. The median follow-up period was 15 months for primary lung cancer and 19
      months for metastatic lung cancer. Local control rates were 91% for metastatic
      lung cancer, 89% for primary lung cancer and 85% for T1, 2N0M0 cases. All
      patients developed mild pneumonitis or fibrosis about 4.5 months after SRT just
      in the treatment volume. Only three patients was symptomatic.

PMID- 11524816
TI  - [Dynamic MR imaging of the upper abdomen: timing optimization and pulse sequence
      selection].
AB  - Since breath-hold gradient-echo MR imaging was introduced, dynamic MR study has
      played an important role in the MR investigation of the upper abdomen. In this
      article, the importance of tailoring imaging delay in each individual patient is
      stressed, with special attention given to a logical aspect of setting delay time
      based upon the bolus transfer time obtained by test injection. Also discussed is
      the importance of selecting types and parameters of pulse sequence to maximize
      the enhancement effect. It should be noted that alteration of gadolinium
      concentration in vivo following intravenous injection could result in a large
      change in signal intensity change on one sequence but little change on another.
      Double-dose 3DFISP with tailored delay time utilizing the test injection method,
      which is currently used for dynamic MR imaging in our institute, is presented.

PMID- 11524817
TI  - [Clinical usefulness of FDG-PET in oncology].
AB  - The clinical diagnosis of tumors is mainly performed using conventional
      radiography, CT, MRI, and ultrasonography, which provide anatomic and morphologic
      information. On the other hand, nuclear medicine imaging, which exploits the
      biochemical aspects of tissue, is considered to be useful for the
      characterization of tumors but is still clinically underutilized. Positron
      emission tomography (PET) with 2-deoxy-2-[18F] fluoro-D-glucose(FDG), an in-vivo
      imaging method that measures glucose metabolism, has been used to detect tumors
      with increased glucose metabolism. Over the past 20 years, numerous reports have
      demonstrated the usefulness of FDG-PET in diagnosing tumors, although FDG-PET has
      only been performed at a small number of institutions. Since FDG-PET has been
      shown to be superior to other morphologic imaging modalities in diagnosing
      tumors, FDG-PET has now become widespread at many institutions and has also been
      incorporated into the clinical pathways for disease management. FDG-PET is a safe
      and cost-effective method with several advantages over morphologic imaging and is
      already covered by many insurance companies in a variety of countries. This
      article discusses the current application of FDG-PET in oncology, especially
      regarding lung cancer, malignant lymphoma, and thyroid cancer. In addition,
      practical approaches for the clinical use of FDG-PET are discussed.

PMID- 11524818
TI  - [MR imaging of posterior cruciate ligament injuries].
AB  - Posterior cruciate ligament(PCL) injuries are less frequent than anterior
      cruciate ligament(ACL) injuries, but are presumably more common than once
      thought. Thirty-nine patients with PCL injuries identified on MR images were
      studied. The criteria for PCL injury were complete tear, partial tear, and
      avulsion fracture. The approximate site of a partial tear was categorized as
      proximal, midsubstance, distal, or combination. Fourteen patients(35.9%) had
      complete tears of the PCL, 21 patients(53.8%) had partial tears, and four
      patients(10.3%) had avulsion fractures. A total of 12 patients (30.7%) had
      isolated PCL injuries, while the remaining 27 patients demonstrated evidence of
      other coexistent knee injuries, such as meniscal tears and ligamentous injuries.
      Of coexistent knee injuries, meniscal tears(18 patients, 46.2%) were most often
      seen.

PMID- 11524819
TI  - [Reirradiation with brachytherapy for recurrent tongue cancer after initial
      brachytherapy].
AB  - The purpose of this study was to assess the efficacy of reirradiation with
      brachytherapy in the treatment of patients with tongue cancer that had recurred
      after initial brachytherapy. A retrospective analysis was performed in 12
      patients with tongue cancer treated by reirradiation with brachytherapy using
      rigid linear sources such as the 226Ra-needle or 192Ir-hairpin at Kyushu
      University Hospital from 1978 to 1998. The patients included 8 men and 4 women,
      who ranged in age from 30 to 69 years (mean, 52 years). At the time of
      reirradiation, 7 patients had stage I cancer, and 5 had stage II cancer,
      according to the UICC (1997) classification. The median follow-up time of the
      surviving patients was 92 months. The 5-year relapse-free and cause-specific
      survival rates were 31% and 64%, respectively. The 5-year cause-specific survival
      rate varied according to the interval between the first and second course of
      brachytherapy and was 25% for intervals of less than 12 months and 83% for
      intervals of more than 12 months. Only 4 patients with local recurrence were
      recognized after their second course of brachytherapy. Among the 6 patients who
      survived more than 2 years after reirradiation without local recurrence,
      symptomatic complications such as soft tissue necrosis and minimal bone necrosis
      were found in 3 patients, but these side effects were not serious enough to
      require surgery. Reirradiation with a second course of brachytherapy may be
      useful in the treatment of patients with tongue cancer that recurs more than 12
      months after initial brachytherapy.

PMID- 11524820
TI  - Investigation of exposure factors in Japanese routine mammography.

PMID- 11524821
TI  - [A case of retroperitoneal splenosis diagnosed by Tc-99m heat-damaged red blood
      cell scintigraphy].
AB  - Splenosis is autotransplantation of splenic tissue that usually follows traumatic
      rupture of the spleen and/or splenectomy. We report a case of retroperitoneal
      splenosis. The correct diagnosis was made noninvasively with Tc-99m heat-damaged
      red blood cell scintigraphy. Surgical treatment, which was not necessary in this
      patient, could be avoided by splenic scintigraphy.

PMID- 11524822
TI  - [Pathology of recent odontogenic maxillary sinusitis and the usefulness of
      endoscopic sinus surgery].
AB  - A Clinicopathological investigation of 34 patients with surgery-requiring
      odontogenic maxillary sinusitis was conducted. 1) Eighty-nine percent of the
      causative teeth leading to odontogenic maxillary sinusitis were teeth that had
      received a root canal treatment. The root canals of most of these teeth were
      incompletely filled with the filling material. 2) The pathological findings for
      the causative teeth showed pulpal necrosis and apical lesions after the root
      canal treatment. 3) Apical lesions in incorrectly treated teeth caused ostitis
      and odontogenic maxillary sinusitis. 4) The cause of odontogenic maxillary
      sinusitis should be questioned, even if a dental procedure has been performed. 5)
      All cases of sinusitis treated with endoscopic sinus surgery improved remarkably.
      Endoscopic sinus surgery is highly indicated for odontogenic maxillary sinusitis.
      6) If the ventilation and drainage of the maxillary sinus is successful after
      surgery, most of the causative teeth (root canal-treated teeth with apical
      lesions) can be preserved only by treatment with antibiotics.

PMID- 11524823
TI  - [Utility of OAE screener (GSI 70) for the evaluation of distortion product
      otoacoustic emissions].
AB  - The purpose of this study was to investigate the ability of the OAE screener GSI
      70 to evaluate of cochlea function in neonates, infants and adults. Distortion
      product otoacoustic emissions (DPOAEs) were measured using the GSI 70 DPOAE
      Analyzer and evaluated in 123 human ears between December 1999 and June 2000. We
      performed the following four general clinical tests to determine the reliability
      of the GSI 70: 1) comparison of DPOAE levels measured using the ILO 92 and the
      GSI 70 in 55 adult ears, 2) comparison of DPOAE levels measured using the GSI 70
      and hearing levels in 55 adult ears, 3) comparison of DPOAE levels measured using
      the GSI 70 and ABR levels in 45 neonate and infant ears, and 4) evaluation of the
      utility of DPOAE measurements obtained using the GSI 70 in functional deafness
      cases. The following results were obtained: 1) DPOAE levels measured with the ILO
      92 and the GSI 70 were closely correlated (correlation coefficient, 0.773 at 2
      kHz and 0.813 at 4 kHz). 2) The sensitivity of the GSI 70 in adult ears confirmed
      to have normal hearing was 80% at 2 kHz and 100% at 4 kHz; the specificity of
      hearing-impaired ears was 94% at 2 kHz and 94% at 4 kHz. 3) The sensitivity of
      the GSI 70 in normal neonate and infant ears with normal hearing was 100% at 2
      kHz and 100% at 4 kHz; the specificity of hearing-impaired neonate and infant
      ears was 97% at 2 kHz and 94% at 4 kHz. 4) All of the functionally deaf ears
      showed excellent DPOAE responses. Examinations using the GSI 70 DPOAE analyzer
      were very easy and fast. Also, the results were highly reliable, with the
      exception of one adult who was classified as having normal hearing in an out-of
      scale hearing level at 2 kHz. We suggest that specific criteria be established
      for the clinical usage of the GSI 70 in performing objective hearing evaluations.

PMID- 11524824
TI  - [Endolymphatic sac drainage and steroid-instillation surgery (EDSS) for
      intractable Meniere's disease].
AB  - Endolymphatic sac surgery is one of the most widely accepted techniques used to
      treat intractable Meniere's disease. To improve this surgery, we developed the
      following techniques: A simple mastoidectomy was used to expose the endolymphatic
      sac between the sigmoid sinus and inferior margin of the posterior semicircular
      canal. The sac was opened and filled with a mass of prednisolone. A bundle of
      absorbable gelatin films was then inserted into the sac lumen to expand it,
      followed by gelatin sponges dipped in a high concentration of dexamethasone. Long
      term results (17-32 months) in 20 patients with intractable Meniere's disease
      treated with endolymphatic sac drainage and steroid-insertion surgery (EDSS)
      showed that definitive spells were completely controlled in 15 of 20 cases (75%);
      all reports of vertigo decreased; hearing improved in 12 of 20 cases (60%); and
      annoyance due to tinnitus decreased in 15 of 20 cases (75%). Steroids directly
      instilled into the endolymphatic cavity may thus be more effective with the
      diseased inner ear organs than those applied via any other route. Draining of
      endolymphatic fluid at the sac into the mastoid cavity also contributed to these
      satisfactory EDSS results.

PMID- 11524825
TI  - [Facial paralysis evaluations using the Yanagihara method, the House-Brackmann
      method, and self-evaluation by patients].
AB  - The Yanagihara method and the House-Brackmann (H-B) method are widely used in
      Japan to evaluate facial paralysis. The present study focuses on the relationship
      between the evaluation of facial paralysis using these methods and self
      evaluation by patients. One-hundred and thirty-one patients with facial paralysis
      were included in the study, consisting of 68 males and 63 females between the
      ages of 17 and 84 years (mean age: 41 +/- 18 years). In addition to the
      Yanagihara and H-B methods, two methods of self-evaluation were used by the
      patients. In the first self-evaluation method, the patient was asked to rate the
      degree of paralysis as a grade of one to six. In the second method, the patient
      was asked to rate the severity of the paralysis on a scale of 0-100. The
      paralysis scores and grades determined using the Yanagihara and H-B methods were
      correlated with the self-evaluations. However, the strength of the correlation
      varied among the patients, indicating that the evaluation of subjective symptoms
      differed among individuals. Even patients who were evaluated as either
      "completely paralyzed" or "cured" according to the Yanagihara and H-B methods did
      not always rate their subjective symptoms as being consistent with these scores.
      In particular, 20 to 30% of patients who were evaluated as "cured" complained of
      minor dyskinesia.

PMID- 11524826
TI  - [Similarity between primary health care and health promotion].
AB  - Primary Health Care is recognized as a core health strategy in developing
      countries, proclaimed by the Declaration at Alma-Ata, while for industrialized
      countries, Health Promotion was stated in the Ottawa Charter. The concept of
      Primary Health Care, having been influenced by the Social Development movement
      for basic human needs in the 70s, is almost entirely consistent with Health
      Promotion, which is in accord with the principles of Human Development pronounced
      in the late 80s through the 90s. Thus, Health Promotion could be developed as a
      health strategy also in developing countries while Primary Health Care could
      similarly be adopted as a health strategy in the industrialized world.

PMID- 11524827
TI  - [Knowledge, attitudes and behavior regarding organ transplantation: the impact of
      the first transplantation from a brain-dead donor under the organ transplantation
      act].
AB  - OBJECTIVE: To investigate knowledge, attitudes and behavior regarding organ
      transplantation, and to estimate the impact of the first organ transplantation
      from a brain-dead donor under the Organ Transplantation Act. SUBJECTS AND
      METHODS: A telephone survey was made using the Random Digit Dialing method in May
      1999. People living in the Tokyo Metropolitan area ages 20 years or over were
      asked about their knowledge, attitudes and behavior regarding organ
      transplantation, and their opinions on the first organ transplantation conduced
      in February 1999. The results were compared with an opinion poll made 7 months
      previously to estimate the impact of this first case. RESULTS: The number of
      respondents was 489 (response rate: 46.0%). 1) Knowledge of organ
      transplantation: most people knew that organ donation from brain-dead donors was
      possible under the act, and that written consent on a form and family member's
      agreement were necessary before donating. More people knew about donor cards. 2)
      Organ transplantation: more people were willing to donate their organs when they
      die, and to agree to donation when a family member died who had wanted to donate
      his/her organs on their death. In the poll 7 months before, fewer people were
      willing to donate their organs or to agree to donate their family member's organs
      after brain death compared with after heart arrest. However, no such difference
      between brain death and heart arrest was found in this later study, suggesting
      that the distinction between the two was no longer considered to be so important.
      3) Respondents themselves having donor cards constituted 15.2%, showing a marked
      increase from 7 months earlier. Another 39.7% wished to carry a donor card; the
      most common reason for not carrying one was they did not know how to acquire it.
      4) The first transplantation was considered to have contributed to the increase
      in knowledge, and a favorable change in attitudes and behavior toward organ
      transplantation. 5) Respondents who agreed to that organ donation from children
      aged under 15 should be possible constituted 46.4%, of the to be this not being
      allowed at the present time. 6) The majority of respondents considered that the
      brain death was diagnosed properly in the first case and that the donation was
      made voluntarily, concluding that the transplantation was made fairly. 7)
      Respondents who considered that the privacy of the donor and the recipients was
      violated were 46.2% and 36.1%, respectively. The attitude of the mass media
      toward the first transplantation was criticized by 56.9% of the respondents. 8)
      Respondents who had a favorable impression of the organ transplantation were
      61.9%. Such people are likely to donate their organs, to agree to a family
      member's donation, and to have a donor card than people who had not gained a
      favorable impression. The two groups exhibited no difference in their knowledge
      concerning organ transplantation. CONCLUSIONS: An increase in knowledge and a
      favorable change in attitudes and behavior regarding organ transplantation was
      confirmed in this survey, as compared with results 7 months earlier, probably
      because the first transplantation took place. The majority of the respondents
      considered that the first transplantation was made fairly, although they
      criticized the attitude of the mass media invading the privacy of the donor and
      the recipients. Further studies should be made to facilitate effective delivery
      of donor cards to people who want to carry them, and to change the rules on organ
      donation from children.

PMID- 11524828
TI  - [Functional characteristics of pharmacy services related to home care in a
      certain suburban area].
AB  - In order to clarify functional characteristics of pharmacy services related to
      home care in a suburban area, a questionnaire survey regarding home-care services
      was conducted for all 75 pharmacies belonged to T-City Pharmaceutical
      Association. The following services were investigated; A) prescription
      (medication guidance for patients and their families, provision of drug
      information to patients, management of the patient's drug history, dispensing,
      advice to physicians, inquiries, management of prescriptions for home infusion
      services); B) supply (sales of items such as over-the-counter [OTC] drugs
      [commercially available drugs that do not require a physician's prescription],
      display and catalogue sales of nursing items); C) consultation (consultation on
      home care, holding events such as health education programs); D) management
      (guidance for drug management by home visit); and E) information exchange
      (information exchange with other medical professionals and social workers). The
      results of the present study were as follows. (1) The following services were
      considered important and therefore regularly performed; A) prescription:
      medication guidance for patients and their families, provision drug information
      to patients, management of the patient's drug history, dispensing, advice to
      physicians, inquiries; and B) supply: sales of items such as OTC drugs. (2) The
      following services were considered important, but not sufficiently regularly
      performed; B) supply: display and catalogue sales of nursing items; C)
      consultation: consultation on home care, holding events such as health education
      programs; D) management: guidance for drug management by home visits; and E)
      information exchange. (3) On factor analysis, among home care-related pharmacy
      services, display and catalogue sales of nursing items as well as consultation on
      home care were present in the same factor group as contained sales of items such
      as OTC drugs, which showed a high accomplishment rate. Guidance for drug
      management by home visits and information exchange with other social workers were
      present in the same factor group as contained information exchange with other
      medical professionals, which showed a relatively low accomplishment rate. In
      summary, home care-related pharmacy services were found to be associated with
      information exchange and supply/consultation functions. This suggests that to
      improve home care-related services in pharmacies, information exchange among
      health, medical practices, and social welfare-associated professionals, not
      previously promoted, should be stimulated and supported.

PMID- 11524829
TI  - [Risk factors for hypertension. A longitudinal study of middle-aged Japanese male
      workers].
AB  - OBJECTIVE: To identify factors related to the development of hypertension among
      middle-aged Japanese men. METHODS AND RESULTS: A cohort of normotensive male
      workers aged 30-59 years (n = 6,306) were followed from 1991 through 1998 to
      observe the development of hypertension, using data from annual health checkups
      in a Japanese company. With hypertension defined as initiation of
      antihypertensive therapy or a systolic blood pressure of 140 mmHg or higher
      and/or a diastolic blood pressure of 90 mmHg or higher, the incidence rate was
      33.4/1000 person-years in the 30-39 year old group, 63.8/1000 person-years in the
      40-49 year old group, and 75.4/1000 person-years in the 50-59 year old group.
      Multivariate analysis by using Cox's proportional hazard model indicated that
      high-normal blood pressure at baseline, obesity (body mass index > or = 25
      kg/m2), drinking 5 days/week or more, and no regular exercise were independent
      factors related to the development of hypertension. Although each age group had a
      different pattern of risk factors, high-normal blood pressure at baseline was the
      strongest risk factor in all cases. Glucose intolerance was significantly
      observed as a hazard only in the 30-39 year old group, hazard rations for obesity
      and physical inactivity also being highest in this younger age group.
      CONCLUSIONS: High-normal blood pressure, obesity, glucose intolerance, regular
      alcohol intake, and physical inactivity are risk factors for hypertension among
      middle-aged Japanese men. Insulin resistance may play an important role in the
      development of hypertension in young males.

PMID- 11524830
TI  - [An individual based analysis of medical expenses of outpatient services for the
      elderly at one health insurance society in Fukuoka Prefecture. Focus on multiple
      or redundant consultations].
AB  - PURPOSE: To ascertain way to reduce medical expenses of the elderly, we analyzed
      old outpatients' receipts covered by the Health and Medical Services Law for the
      Aged at one health insurance society in Fukuoka prefecture. In addition, an
      attempt was made to find better ways to share medical information and construct a
      system of receipt analysis. SUBJECTS AND METHODS: We used 312 receipts for 179
      old outpatients in July in 1997. The number of prescriptions was internalized
      into the number of outpatients' receipt. We classified the patients as "multiple"
      who consulted several clinics a month and as "redundant" who consulted several
      clinics for the same diseases. RESULTS AND CONCLUSION: 1) The expenses of
      outpatients accounted for about 1/3 of the total. Average values for patients
      were 78.3 years old of age, 7.7 diseases, 1.5 pharmacies, 1.7 clinics, 7
      consulting days, and the medical expenses of 40,482 yen per month. 2) The rate of
      multiple including redundant consultations was 49.7% and that for those that were
      redundant was 9.5%. Redundant consultations increased as the number of
      consultation clinics increased. 3) Factors considered to increase medical
      expenses were the number of diseases, the consulting days, and the number of
      consultation/prescription organizations. Multiple and redundant consultations
      amounting to half of the whole fulfilled all of these criteria. 4) The average
      medical expense for non-multiple and non-redundant patients was 28,314 yen, as
      compared with 52,786 yen for multiple and redundant and 64,306 yen for redundant
      cases. If there were no multiple consultations, thirty percent of the expenses
      could be avoided and if there were no redundant consultations, the reduction
      might be 6%, although more detailed clinical records are necessary for firm
      conclusions. To reduce excess expenditure, instructions for patients having home
      doctors and passing through introductions are important. 5) Regarding the expense
      of medical services, medication was accounted for 39.2% as the greatest outlay.
      Cautions for suitable use of drugs are required for multiple and redundant
      patients, because they tend to visit many pharmacies. Considering the rate rise
      of separation of pharmacy and clinic, fixing of field division of work and the
      sharing of medical information are inadequate. For example, introduction of an IC
      card system might be very useful to facilitate the development of community-based
      medical information system. 6) It is strongly suggested that a computerized
      information system with a standardized format should be developed on the
      initiative of a national organization such as the National Federation of Health
      Insurance Societies.

PMID- 11524831
TI  - [Validity of various indices of obesity calculated from height and weight data
      for adult males use of the underwater-weighing method as a reference].
AB  - PURPOSE: We evaluated associations between excess body fat (%Fat) and various
      indices of obesity calculated from height and weight data. METHODS: In 147 adult
      males, %Fat was measured by the underwater-weighing method, and obesity indices
      were generated by the following 5 approaches: the Broca-Katsura (Katsura method),
      the Kato-Wataya (Kato method), Japan Society for the Study of Obesity (BMI
      method; based on the body weight at which the BMI is 22), and the Meiji Life
      Insurance Co. methods, and the Tables and Figures for Assessment of Obesity and
      Leanness published by the Ministry of Health and Welfare (MHW method). RESULTS:
      %Fat was 20% or more (obese) in 67 males (45.6%), 15-20% in 39 (26.5%), 10-15% in
      35 (23.8%), and less than 10% in 6 (4.1%). The correlation coefficients between
      the obesity indices and %Fat were 0.612 for the Katsura method, 0.590 for the
      Kato-method, 0.611 for the BMI method, 0.612 for the Meiji Life Insurance Co.
      method, and 0.550 for the MHW method, being significant in each case (P < 0.01).
      When the cut-off point was set as 110% for each obesity index, sensitivity was
      highest with the Kato-method (82.1%), and specificity was highest with the Meiji
      Life Insurance Co. method (93.8%). With the MHW method, the receiver operating
      characteristic (ROC) curve was slightly farther from the point of sensitivity of
      100% and 1-specificity of 0% than the others. CONCLUSION: Excess fat accumulation
      can not be accurately assessed by obesity indices calculated from body height and
      weight data. Validity was similar among obesity indices examined.

PMID- 11524832
TI  - [Current topics of complicated congenital heart disease].

PMID- 11524833
TI  - [Surgical treatment of coarctation and interrupted aortic arch complex in
      infants].
AB  - One hundred forty-two consecutive neonates or early infants with coarctation and
      interrupted aortic arch complex who underwent biventricular repair at the Fukuoka
      Children's Hospital between January 1991 and December 2000 were reviewed. One
      stage repair was performed in 33 patients (35%) with coarctation complex and in
      41 patients (85%) with interrupted aortic arch complex. The overall mortality
      rate was 6.1% in one-stage repair and 6.6% in two-stage repair of coarctation
      complex patients and 9.8% in one-stage repair and 28.6% in two-stage repair of
      interrupted aortic arch complex patients. The recoarctation rate was 5.3% in
      coarctation complex and 2.1% in interrupted aortic arch complex. All patients
      with recoarctation underwent successful catheter intervention and required no
      reoperation. In conclusion, one-stage repair of interrupted aortic arch and
      coarctation complex with the anterior approach resulted in good outcomes. Then
      descending aorta cannulation through a median sternotomy combined with the
      cerebral perfusion technique enables complete avoidance of circulatory arrest and
      is a useful technique. However, a two-stage procedure can be useful in the
      patients whose condition has deteriorated substantially or in whom intracardiac
      anomalies are severe.

PMID- 11524834
TI  - [Current trends in heart surgery for the treatment of congenital anomalies:
      tetralogy of Fallot and its variants].
AB  - The surgical repair of tetralogy of Fallot is one of the most common procedures
      to correct congenital cardiac anomalies. However, controversy remains regarding
      the benefits and drawbacks of early primary repair. The management of patients
      with pulmonary atresia has become more aggressive in recent years, i.e., earlier
      primary repair with complete unifocalization is performed even if they have
      associated major aortopulmonary collateral arteries. On the other hand, the
      durability of small-sized conduits is unsatisfactory, and the rate of freedom
      from reoperation for those who received conduits in infancy is still low.
      Ventricular arrhythmia and sudden cardiac death late after repair of tetralogy of
      Fallot are disastrous complications in adult survivors, but it remains difficult
      to predict which patients will experience such complications. Sustained
      ventricular tachycardia with pulmonary regurgitation is the predominant
      hemodynamic lesion. Achieving complete relief of the pressure gradient in the
      right ventricular outflow tract with no pulmonary regurgitation is the ultimate
      goal of surgical treatment of tetralogy of Fallot and its variants.

PMID- 11524835
TI  - [Double outlet right ventricle].
AB  - There are eight fundamental types of double-outlet right ventricle based on the
      ventriculoarterial relationship, deviation of the great artery, and
      atrioventricular relationship. Combination of the dextroposition of the posterior
      great artery and levoposition of the anterior great artery provides conotruncal
      criss-cross. The appropriate biventricular repair can be selected in the setting
      of two types of double outlet right ventricle, the dextroposition and conotruncal
      criss-cross type.

PMID- 11524837
TI  - [Total anomalous pulmonary venous connection].
AB  - Recently the surgical results of simple (isolated) total anomalous pulmonary
      venous connection have improved markedly, and even the most severely affected
      patients presenting with marked hypoxia soon after birth have become salvagable
      partly due to the perioperative use of nitric oxide and extracorporeal membrane
      oxygenation. However, the outcome after complex surgery, particularly in
      asplenia, is still very poor in newborns. Common pulmonary vein atresia is still
      an ominous diagnosis and according to the literature only a few patients have
      survived surgery. The results of reoperation for postoperative pulmonary vein
      stenosis are also poor, although the good results of the "sutureless technique"
      which have recently been reported are encouraging. Prenatal diagnosis using
      echocardiography is difficult, but postnatal diagnosis using echocardiography and
      magnetic resonance imaging is usually precise and can obviate the need for
      cardiac catheterization which often aggravates the hypoxic status in critically
      ill infants.

PMID- 11524836
TI  - [Surgical treatment of transposition of the great arteries: the arterial switch
      operation].
AB  - Transposition of the great arteries (TGA) is one of the most common congenital
      cardiac anomalies resulting in cyanosis. Various atrial-level physiological
      procedures were developed in the late 1950s and early 1960s, including the
      Senning and Mustard procedure. In 1975, Jatene et al. reported the first
      successful arterial switch procedure in a patient with d-TGA and ventricular
      septal defect. In 1977, Yacoub et al. introduced a two-stage repair comprising
      initial pulmonary artery banding to retain the left ventricle, supplemented by a
      systemic-pulmonary artery shunt, thereby potentially expanding the arterial
      switch procedure to a much wider population of patients. In 1983, the concept of
      the primary neonatal arterial switch procedure was introduced by Castaneda et al.
      Since then, the primary artery switch procedure in neonates and early infants has
      become the standard for the treatment of TGA. This is due to the fact that the
      only the arterial switch procedure allows complete anatomical repair. In Japan,
      102 neonates with simple TGA underwent the arterial switch procedure, with
      hospital death occurring in 21 (20.6% mortality rate) according to the 1998
      annual report. In Okayama University Hospital, 48 neonates, underwent the
      arterial switch procedure, with 1 hospital death (2.1% mortality rate) and no
      late deaths since 1991.

PMID- 11524838
TI  - [Congenital aortic stenosis].
AB  - Recent advances in and controversies concerning the management of children with
      congenital valvular aortic stenosis are discussed. In neonates with critical
      aortic stenosis, improved survival has recently been reported after surgical open
      valvotomy and balloon valvuloplasty, although it is difficult at this point to
      compare the results of the two procedures and determine their differential
      indications. Good results have also been achieved after extended aortic
      valvuloplasty for recurrent aortic stenosis and/or insufficiency, but the length
      of follow-up in these patients is still short. The technique first reported in
      1991 for bilateral enlargement fo a small annulus permits the insertion of an
      aortic valve 3-4 sizes larger than the native annulus. It entails no risk of
      distorting the mitral valve, damaging the conduction system or important branches
      of the coronary arteries, or resulting in left ventricular dysfunction. The Ross
      procedure is now widely applied in the West, with reports of early mortality
      rates of less than 5% and event-free survival rates of 80-90% during follow-up of
      4-8 years. Longer follow-up and continued careful evaluation are required to
      resolve the issue of possible dilatation and subsequent neoaortic valve
      dysfunction and pulmonary stenosis due to allograft degeneration after pulmonary
      autograft root replacement in children.

PMID- 11524839
TI  - [Tricuspid atresia and univentricular heart].
AB  - Recent modification of the Fontan operation was followed by remarkable
      improvement of surgical results in patients with tricuspid atresia and
      univentricular heart. Application of TCPC-type procedures contributed to this
      progress and new developments will yield better long-term postoperative results.
      Surgical strategies with the Fontan operation should include various preparatory
      procedures, such as systemic-pulmonary shunt, pulmonary arterial banding, plasty
      or reconstruction of pulmonary arteries, bidirectional Glenn anastomosis,
      creation of additional aortopulmonary anastomosis, and coil embolization of
      aortopulmonary collateral arteries.

PMID- 11524840
TI  - [Surgical treatment of hypoplastic left heart syndrome].
AB  - Hypoplastic left heart syndrome (HLHS) was previously uniformally fatal within
      the first month of life. The development of the Norwood stage I operation has
      afforded new hope to the families of newborn infants with this defect. Recent,
      modification of the Norwood procedure has improved the surgical results. The one
      year survival rate after the Norwood procedure is from 50% to 70% in major
      institutions. The results of second palliation (hemi-Fontan operation or
      bidirectional Glenn operation) are nearly acceptable. Recently, fetal
      echocardiography has allowed early diagnosis of HLHS, and after a prenatal
      diagnosis of HLHS, couples may be offered termination of the pregnancy. It is
      necessary to improve the results of the Norwood stage I operation, to save more
      fetuses and neonates with HLHS.

PMID- 11524841
TI  - [How can we work effectively in the Third World?].

PMID- 11524842
TI  - [Acquired von Willebranol syndrome--its pathophysiology, diagnosis and
      treatment].

PMID- 11524843
TI  - [Successful treatment of hairy cell leukemia with pentostatin].
AB  - A 45-year-old woman was admitted to our hospital in August, 1999. Laboratory data
      showed a white blood cell count of 5,050/microliter with 78% abnormal
      lymphocytes, hemoglobin 6.8 g/dl, platelets 4.8 x 10(4)/microliter, and soluble
      IL-2 receptor 97,600/ml. The abnormal cells were characterized by a hairy
      appearance under phase contrast microscopy, and showed strong tartrate-resistant
      acid phosphatase activity. Immunophenotype analysis revealed that these cells
      were positive for CD11c, CD19 and CD25, and negative for CD5. Bone marrow biopsy
      showed diffuse proliferation of hairy cells with moderate myelofibrosis. We
      diagnosed the patient as having European-American-type hairy cell leukemia.
      Pentostatin was administered at a dose of 5 mg/m2 weekly. After twelve doses, the
      peripheral blood data returned to the normal range with no hairy cells in the
      blood or bone marrow, although slight splenomegaly remained. The patient
      underwent splenectomy in December of the same year, and we were unable to find
      any hairy cells by histological and immunohistochemical examination. Although
      most patients with hairy cell leukemia in Japan have the Japanese variant, and
      the European-American type is rare, pentostatin is as effective as it is for
      European and American patients.

PMID- 11524844
TI  - [Nontuberculous atypical mycobacterial infection with progressive pancytopenia in
      a patient with myelodysplastic syndrome].
AB  - We describe a patient with myelodysplastic syndrome (MDS) who developed
      disseminated infection due to nontuberculous mycobacteria (NTM). A 64-year-old
      man was admitted because of persistent fever that had been unresponsive to
      antibiotics. Bone marrow aspiration specimens showed myelodysplasia (RA), but the
      origin of the fever was unclear. Cytopenia worsened to a level that required
      transfusion of red blood cells and platelets. Repeated bone marrow examination
      revealed hypoplasia with hemophagocytosis. Several weeks later, photochromogenic
      NTM was isolated from bone marrow specimens, sputum and broncho-alveolar lavage
      (BAL) fluid which had been obtained on admission. Antituberculosis treatment with
      clarithromycin markedly improved the patient's general condition and
      hematological abnormalities. Three months after resolution of the NTM infection,
      the peripheral blood monocyte count increased, the fever recurred, and the
      patient suddenly died of myocardial infarction. Disseminated infection with NTM
      has gained attention as a frequent complication of AIDS, and NTM can also be one
      of the pathogens causing disseminated infection in patients with MDS. In the
      present case, infection with mycobacteria that normally would have been digested
      by macrophages and would not have caused disseminated infection in a healthy
      individual, was probably related to the clinical features including high fever,
      severe pancytopenia and hemophagocytosis.

PMID- 11524845
TI  - [Complete cytogenetic response to interferon-alpha in a patient with chronic
      myelogenous leukemia undergoing hemodialysis].
AB  - We describe a complete cytogenetic response to interferon-alpha in a patient with
      chronic myelogenous leukemia undergoing chronic hemodialysis. Although IFN-alpha
      therapy has been applied to patients with chronic hepatitis C receiving
      hemodialysis, the pharmacokinetics of IFN-alpha in patients with poor renal
      function still remain unclear. In the present patient, the serum IFN-alpha
      concentration remained high even 48 hours after injection (42.9 IU/ml), and IFN
      alpha was almost completely removed by hemodialysis (< 6 UI/ml). The patient was
      treated with IFN-alpha (3 x 10(6) IU, three times a week), and cytogenetic
      disappearance (0%) of the Ph-positive clone was confirmed 31 months after the
      start of therapy. Recombinant human erythropoietin (Epo) was used to treat anemia
      due to renal failure and IFN-alpha therapy. The anemia was controllable with Epo,
      and no adverse effect was observed.

PMID- 11524846
TI  - [Gross spreading multiple extramedullary plasmacytomas to the skin in the
      terminal stage of multiple myeloma].
AB  - A 71-year-old woman with an 8-year history of IgG-kappa type multiple myeloma was
      admitted because of severe lumbago and bone destruction. Her serum IgG level was
      elevated to 5,565 mg/dl at admission. Despite treatment with doxorubicin,
      vincristine, dexamethasone, melphalan and interferon-alpha, the response was
      transient. Nine months later, multiple skin nodules appeared on her chest,
      abdominal wall and right thigh accompanied by elevation of the serum IgG level.
      Response to combination chemotherapy with cyclophosphamide, ranimustine,
      vincristine and prednisolone was also transient. The skin tumors on the bilateral
      thighs, especially on the left side, acquired chemotherapy resistance and
      gradually enlarged. Although the serum IgG level was maintained by chemotherapy
      within the range 1, 790-2,676 mg/dl, the skin tumors on the left thigh had spread
      very rapidly and appeared "rock-like". The enlarged tumors caused necrosis with
      erosions and oozing hemorrhage. A skin biopsy from the tumors on the left thigh
      showed plasmacytoma in which infiltration of large anaplastic plasma cells was
      observed. The patient died of sepsis 8 months after the skin tumors initially
      developed. This is a very rare case of multiple myeloma in which multiple large
      plasmacytomas of the skin developed and grew aggressively at the terminal stage
      after a long-term indolent course.

PMID- 11524847
TI  - [Basophilic differentiation of leukemic cells in a patient with acute leukemia
      carrying minor bcr/abl chimeric mRNA].
AB  - A 77-year-old woman was referred to our hospital because of leukocytosis and
      leukoblastosis in September 1999. She was healthy except for hypertension, and no
      abnormal findings in the peripheral blood had been observed up to December 1998.
      Physical examination revealed neither hepatosplenomegaly nor superficial
      lymphadenopathy. A bone marrow film showed massive proliferation of blast cells
      (87.8%), some of which contained coarse basophilic granules (38.6%). The cells
      were negative for peroxidase and esterase (alpha-naphtyl butyrate and ASD
      chloroacetate) staining, but the granules showed metachromasia upon toluidine
      blue staining. As immunophenotypic analysis of the cells showed double positive
      for CD13/CD19 but negativity for CD33, this case did not meet the diagnostic
      criteria for biphenotypic acute leukemia. Chromosome and gene analysis showed
      positivity for the Ph1 chromosome with minor bcr/abl chimeric mRNA. A homogenate
      of the peripheral mononuclear cells demonstrated a high concentration of
      histamine. Electron microscopy analysis confirmed that some of the blast cells
      contained dense granules, which closely resembled "immature basophil granules"
      morphologically. These results suggested that the blast cells showed basophilic
      differentiation. As the clinical course and peripheral blood findings were
      different from blastic crisis of chronic myelogenous leukemia (CML) and CML with
      minor bcr/abl chimeric mRNA, the present case was diagnosed as "multiphenotypic
      acute leukemia", a type of acute basophilic leukemia classified by Duchayne.

PMID- 11524848
TI  - [Primary lymphoma of the vagina].
AB  - Primary vaginal non-Hodgkin's lymphomas (NHL) are rare, and are clinically
      difficult to differentiate from inflammatory diseases or vaginal cancer. Here, we
      present such a case in a 74-year-old woman complaining of fever and difficulty
      with urination. Pelvic examination revealed a tumor involving most of the vaginal
      wall, and pelvic MRI demonstrated vaginal wall thickening. A biopsy of this
      lesion confirmed NHL (diffuse large B-cell lymphoma), and the patient was
      admitted. Abdominal CT and MRI detected a vaginal tumor, and Ga scintigraphy
      confirmed accumulation in the pelvis, but no abnormalities were seen in other
      areas. Therefore, the patient was diagnosed as having NHL at clinical stage IB
      with low-intermediate risk (international prognosis index) (LDH 1,309 IU/L). The
      patient underwent three courses of CHOP therapy followed by radiotherapy, and
      complete remission was achieved. Primary vaginal NHL often affects women younger
      than 50 years of age, and abnormal hemorrhage is the initial symptom in many
      cases. There have been a number of reports of long-term survival following
      appropriate early chemotherapy and radiation therapy, suggesting that early
      diagnosis and treatment based on vaginal biopsy findings greatly influence the
      prognosis.

PMID- 11524849
TI  - [Successful treatment using iron depletion phlebotomy combined with recombinant
      erythropoietin after allogeneic bone marrow transplantation for myelodysplastic
      syndrome complicated by secondary hemochromatosis].
AB  - A 33 year-old female patient presented with apparent skin pigmentation, sustained
      liver dysfunction and impaired glucose tolerance. She had received blood
      transfusions totalling more than 40,000 ml for myelodysplastic syndrome and an
      allogeneic bone marrow transplant from her HLA-matched sister at the age of 31.
      Ferrokinetic data showed a significant iron overload. Magnetic resonance imaging
      suggested excessive iron deposition in the liver. The patient was diagnosed as
      having secondary hemochromatosis. She was given subcutaneous injections of 6,000
      units of recombinant human erythropoietin initially twice a week and then weekly,
      and phlebotomies were performed to maintain her hemoglobin level above 10 g/dl.
      Three years later, the total volume of phlebotomized blood reached 24,000 ml, and
      her ferrokinetic data, serum transaminase levels, glucose tolerance and skin
      color were significantly improved.

PMID- 11524850
TI  - [Role of appendix in ulcerative colitis].

PMID- 11524851
TI  - [Ulcerative colitis and appendiceal lesion].

PMID- 11524852
TI  - [Gastrointestinal pacemaker system].

PMID- 11524853
TI  - [Efficacy of the urine antibody test for detection of Helicobacter pylori:
      comparison with serum antibody tests].
AB  - A urine-based enzyme-linked immunosorbent assay kit (URINELISA) for detection of
      the antibody for H. pylori has recently been developed. We evaluated the
      diagnostic capability of the URINELISA test in comparison with two serum IgG
      antibody kits (HM-CAP and Helico G) for H. pylori infection. The subjects of this
      study were 173 patients. H. pylori was detected by means of culture,
      immunohistochemical staining and rapid urease test of endoscopically obtained
      biopsy specimens. A positive diagnosis of H. pylori was when at least one of
      three tests was positive and a negative diagnosis when all three were diagnosed
      as H. pylori positive and 23 as negative. We also examined the diagnostic
      potential of the antibodies in urine and in serum by using the results of the
      bioptic methods as the gold standard. The sensitivity of both URINELISA and HM
      CAP was 93.3% and that of Helico G 94.7%, while their respective specificities
      were 47.8%, 65.2% and 52.2%. The URINELISA kit thus showed high sensitivity but
      relatively low specificity. The latter was due to sampling errors in the bioptic
      procedure because the subjects of this study included many elderly patients with
      atrophic gastritis. The level of the antibody in urine decreased markedly after 2
      months of eradication therapy. We conclude that the URINELISA kit is as effective
      as serum antibody kits for the diagnosis of H. pylori infection.

PMID- 11524854
TI  - [Administration of proton pump inhibitor caused esophageal stenosis in two
      patients with severe reflux esophagitis].

PMID- 11524855
TI  - [A case of pneumatosis cystoides intestinalis involving the small intestine,
      large intestine and stomach].

PMID- 11524856
TI  - [A case of intestinal Behcet disease with duodenal ulcer perforation].

PMID- 11524857
TI  - [A case of carcinoma of the ileum invading proper muscular layer].

PMID- 11524858
TI  - [A case of adenosquamous carcinoma of the liver containing squamous components
      demonstrating a character of adenocarcinoma with immunohistochemical stains].

PMID- 11524859
TI  - [A case of traumatic common bile duct stricture due to traffic accident].

PMID- 11524860
TI  - [A case of Budd-Chiari syndrome associated with anti-phospholipid syndrome].

PMID- 11524861
TI  - Effects of a high-bicarbonate dentifrice on intraoral demineralization.
AB  - Dentifrices available on the market today contain sodium bicarbonate in a wide
      range of concentrations. Anticaries efficacy has been demonstrated for these
      dentifrices in a variety of tests. New insights were gained in the present study
      in which the effect of a high-bicarbonate dentifrice on the sucrose-induced
      demineralization of tooth enamel in situ was examined. With the intraoral Delta
      Ip system it is possible to follow the minute changes in tooth enamel that
      essentially model the daily episodes of demineralization accompanying the
      ingestion of various foods. The results revealed a pronounced effect on the pH of
      the test plaque and a considerable reduction in mineral loss from the enamel. The
      effect persisted from more than 1 hour and, during that time, appeared to
      predominate over the effect of fluoride. These findings suggest that bicarbonate
      may provide additional protection against the loss of tooth enamel. Such effects
      may be significant for the design of new high-bicarbonate products.

PMID- 11524862
TI  - Antibacterial activity of baking soda.
AB  - The antibacterial activity of baking soda (sodium bicarbonate) was assessed using
      three different experimental approaches. Standard minimum inhibitory
      concentration analyses revealed substantial inhibitory activity against
      Streptococcus mutans that was not due to ionic strength or high osmolarity. Short
      term exposure assays showed significant killing of bacterial suspensions when
      baking soda was combined with the detergent sodium dodecylsulfate. Multiple,
      brief exposures of sucrose-colonized S mutans to baking soda and sodium
      dodecylsulfate caused statistically significant decreases in numbers of viable
      cells. Use of oral health care products with high concentrations of baking soda
      could conceivably result in decreased levels of cariogenic S mutans in saliva and
      plaque.

PMID- 11524863
TI  - The use of sodium bicarbonate in oral hygiene products and practice.
AB  - Early dentifrices contained natural ingredients, mostly in coarse particle form,
      and were quite abrasive. Salts, either sodium chloride, sodium bicarbonate, or a
      mixture of both, have also been used for tooth cleaning because of their ready
      availability and low cost. Because of both their relatively low intrinsic
      hardness and their high solubility, another advantage is low abrasivity. Their
      biggest disadvantage is a salty, unpalatable taste. Many modern dentifrices that
      contain sodium bicarbonate, either as the sole abrasive or one of several,
      disguise the saltiness with flavoring and sweetening agents. An almost inverse
      relationship exists between the percentage of baking soda in a dentifrice and its
      abrasivity. Sodium bicarbonate has no anticaries activity per se but is
      compatible with fluoride. In high concentrations, sodium bicarbonate is
      bactericidal against most periodontal pathogens. Most clinical studies have not
      found significant differences in periodontal response to baking soda as compared
      with other commercial dentifrices, probably because of its rapid clearance from
      the gingival sulcus. Sodium bicarbonate may not be the "magic bullet" for curing
      dental diseases, but its safety (if ingested), low abrasivity, low cost, and
      compatibility with fluoride make it a consummate dentifrice ingredient.

PMID- 11524864
TI  - Effects of baking-soda-containing dentifrices on oral malodor.
AB  - Oral malodor, also known as bad breath or halitosis, is an extremely common
      problem. Bad breath can arise from many sources in the body, but most frequently
      is produced in the mouth by the action of gram-negative anaerobic bacteria on
      sulfur-containing proteinaceous substrates in the saliva, such as debris and
      plaque. The primary molecules responsible for oral malodor are volatile sulfur
      compounds (VSC), such as hydrogen sulfide and methylmercaptan. Increased malodor
      production is related to greater bacterial numbers, reducing conditions,
      availability of protein substrates, and a pH above neutral. Bad breath is more
      common in the elderly, as well as those with unhygienic mouths, gingivitis, and
      periodontitis, but bad breath can also be found in some individuals who are
      periodontally healthy. The major source of oral malodor is the tongue. Approaches
      to controlling malodor have included masking, oral hygiene, antibacterial agents,
      conversion of VSC to nonodorous forms, oxidizing agents, and traditional
      approaches, including the use of baking soda. Results of controlled double-blind
      crossover studies, using both organoleptic (sensory) and gas chromatographic
      analysis of mouth air VSC, indicate that two dentifrices with high baking-soda
      concentrations, Arm & Hammer Dental Care and Arm & Hammer PeroxiCare, reduce oral
      malodor.

PMID- 11524865
TI  - Management of dental staining: can low-abrasive dentifrices play a role?
AB  - Dental staining, while always a significant problem, has become more important in
      recent years with the introduction and increased use of chlorhexidine-based
      mouthrinses. Not only do these rinses themselves cause staining, they also
      enhance staining from other sources, such as diet or tobacco use. An
      understanding of the etiologies of dental stains will help today's practitioners
      become more effective in managing dental stains in their practices. Important
      strategies for managing stain are patient education about the causes of staining,
      careful consideration of product recommendations for home use, and routine office
      visits for prophylaxis. Ideal products for patient use are those with effective
      stain-removal properties and low abrasivity, which minimizes tooth wear.

PMID- 11524866
TI  - A microbiological and clinical study of the safety and efficacy of baking-soda
      dentifrices.
AB  - This article reports the results of a study that examined the clinical and
      microbiological changes associated with regular use of baking-soda dentifrices.
      Two dentifrice formulations were examined in a 6-month longitudinal study of 101
      adult subjects with assessments for plaque, gingival inflammation, and stain at
      baseline and 3 and 6 months during the active phase of the study, and at 3 months
      after cessation of product use. One dentifrice contained 52% baking soda and 3%
      sodium percarbonate (Arm & Hammer PeroxiCare) while the other dentifrice
      contained 65% baking soda (Arm & Hammer Dental Care). Both dentifrices resulted
      in statistically significant reductions in dental plaque, gingival inflammation,
      and stain at all time periods compared to baseline. Dental plaque and buccal soft
      tissue samples were obtained for microbiological analysis from a 50-subject
      subset. Microbiological assays, including bacterial culture, phase-contrast
      microscopy, and immunofluorescence microscopy, confirmed the safety of both
      formulations. Beneficial alterations in dental plaque bacteria were noted,
      including significant reductions in the levels of Actinomyces species. The data
      from this study indicate that dentifrices containing high levels of baking soda
      are clinically effective and microbiologically safe.

PMID- 11524867
TI  - Effect of a bicarbonate-containing dentifrice on pH changes in a gel-stabilized
      plaque after exposure to sucrose.
AB  - Because many factors influence the acid-forming ability of dental plaque in the
      mouth, a model system was used in which reproducible Stephan curves could be
      generated after exposure of a gel-stabilized plaque to sucrose. Simulation of the
      use of a high-bicarbonate dentifrice at a time when plaque pH had fallen to about
      4.5 caused a rapid return of the pH toward neutrality, whereas simulation of the
      use of a low-bicarbonate dentifrice had much less effect.

PMID- 11524869
TI  - How Bush got there.

PMID- 11524868
TI  - "We must proceed with great care".

PMID- 11524870
TI  - America's best. Who says there are no Einsteins anymore?

PMID- 11524871
TI  - Stem winder.

PMID- 11524872
TI  - Man hunter.

PMID- 11524873
TI  - Baby monitor.

PMID- 11524874
TI  - Super surgeon.

PMID- 11524875
TI  - Gene detective.

PMID- 11524876
TI  - Heart mender.

PMID- 11524877
TI  - Cancer spotter.

PMID- 11524878
TI  - The iceman.

PMID- 11524879
TI  - Ecosystems analyst.

PMID- 11524880
TI  - Power broker.

PMID- 11524881
TI  - Mr. Universe.

PMID- 11524882
TI  - Fossil finder.

PMID- 11524883
TI  - Drug deliveryman.

PMID- 11524884
TI  - Mind reader.

PMID- 11524885
TI  - Life preserver.

PMID- 11524886
TI  - Nerve builder.

PMID- 11524887
TI  - Protein wizard.

PMID- 11524888
TI  - Lifetime Achievement Award. E. O. Wilson.

PMID- 11524889
TI  - Europe goes to pot.

PMID- 11524890
TI  - The new rules for keeping secrets.

PMID- 11524891
TI  - A step or two against diabetes.

PMID- 11524892
TI  - Take your medicine. HMOs are using a new service to manage their sickest
      patients.

PMID- 11524893
TI  - [German and international child and adolescent psychiatry].

PMID- 11524894
TI  - [Current research in search of neurobiological correlates of reading and spelling
      disorder].
AB  - OBJECTIVE: The present article provides an overview of the main approaches in the
      current literature on the neurobiological correlates of developmental dyslexia.
      METHODS: Approximately 120 articles, published mainly within the past six years,
      were analyzed. RESULTS: Three topics are of focal interest: first, the point of
      unusual asymmetries of the temporal plana and deviations of the corpus callosum;
      second, the analysis of abnormal patterns of activation of the left hemispherical
      frontal and temporal lobes. In this context, a dysfunction of the angular gyrus
      is discussed. The third approach postulates that global deficits of subcortical
      systems concerning the temporal procession of acoustic and visual information
      play a major role in the cause of dyslexia. CONCLUSIONS: The first approach is
      not specific enough with regard to negative results, whereas the second and third
      seem particularly promising.

PMID- 11524895
TI  - [Day clinic treatment in child and adolescent psychiatry].
AB  - OBJECTIVES: The history of day treatment in child and adolescent psychiatry in
      Germany is brief. Accordingly, day treatment programs deal primarily with
      programming, outcome studies and indications/contraindications. METHODS: This
      article reviews the English- and German-language literature between 1960 and 2000
      relevant to the outcome of day treatment in child and adolescent psychiatry.
      Outcome studies are discussed. RESULTS: Outcome studies do not yet allow
      decisions about for whom day treatment does or does not exactly work.
      Nonetheless, evidence from the literature suggests that day treatment does work
      for many different disorders in child and adolescent psychiatry. The predictive
      value of parental involvement in therapy for outcome is supported by several
      studies. CONCLUSIONS: In addition to randomized controlled outcome studies,
      effectiveness studies of single day treatment programs are useful and should
      deliver the data on the kinds of children, treatment goals and results for which
      a program in a specific regional mental health care system is effective.

PMID- 11524896
TI  - [Evaluated treatment approaches in child and adolescent psychiatry I].
AB  - OBJECTIVES: The principle of evidence-based medicine is to integrate data
      concerning the efficacy of interventions into clinical practice. This article
      assesses the level of evaluation of psychosocial, psychopharmacological and
      combined interventions for mental disorders in childhood and adolescence
      (autistic disorders, hyperkinetic disorders, conduct disorders, tic disorders,
      enuresis, and encopresis). METHODS: Three different levels of evaluation were
      defined for both psychosocial and psychopharmacological interventions: A (> or =
      2 randomized controlled studies), B (1 randomized controlled study), and C (open
      studies and case studies). The level of evaluation was judged on the basis of
      original papers found in a comprehensive literature search. RESULTS: For most
      disorders presented in this article there are several A-level treatments. The
      efficacy of both psychosocial and psychopharmacological interventions that target
      specific problem behaviors or symptoms, respectively, has been repeatedly
      demonstrated with regard to autistic disorders. Many studies have evaluated
      treatment approaches for hyperkinetic disorders and conduct disorders. With
      regard to the treatment of tic disorders in children and adolescents, far more
      studies evaluated the efficacy of pharmacotherapy than of psychotherapy.
      CONCLUSIONS: Further research should compare the efficacy of different treatment
      approaches, examine specific and differential treatment effects and investigate
      combined treatment approaches.

PMID- 11524897
TI  - [Evaluated treatment approaches in child and adolescent psychiatry II].
AB  - OBJECTIVES: The principle of evidence-based medicine is to integrate data
      concerning the efficacy of interventions into clinical practice. This article
      assesses the level of evaluation of psychosocial, psychopharmacological and
      combined interventions for mental disorders in childhood and adolescence
      (schizophrenic disorders, affective disorders, phobias and anxiety disorders,
      obsessive-compulsive disorder, posttraumatic stress disorder, anorexia nervosa,
      and bulimia nervosa). METHODS: Three different levels of evaluation were defined
      for both psychosocial and psychopharmacological interventions: A (> or = 2
      randomized controlled studies), B (1 randomized controlled study), and C (open
      studies and case studies). The level of evaluation was judged on the basis of
      original papers found in a comprehensive literature search. RESULTS: The number
      of controlled studies examining these disorders in children and adolescents is
      small, especially with regard to pharmacotherapy. However, the efficacy of
      (cognitive) behavior therapy for depressive disorders, phobias and anxiety
      disorders, as well as posttraumatic stress disorder has been demonstrated.
      CONCLUSIONS: There is still a considerable need to evaluate pharmacological
      treatment approaches for schizophrenic and affective disorders. Looking at
      psychosocial interventions in schizophrenic disorders, obsessive-compulsive
      disorder and eating disorders, specific aspects of treatment for young patients
      should be examined. Overall, the psychotherapy approach evaluated best is
      (cognitive) behavioral therapy.

PMID- 11524898
TI  - [Factor structure of the Autism Diagnostic Interview-Revised (ADI-R): a study of
      dimensional versus categorical classification of autistic disorders].
AB  - OBJECTIVES: This study investigated whether empirically derived dimensions of
      autistic behavior are consistent with the content-valid construction of the
      autistic behavior domains according to ICD-10 and DSM-IV (social interaction,
      communication and repetitive, stereotyped behavior). METHODS: A principal
      component exploratory factor analysis routine with varimax-rotation and
      extraction of factors following the Scree criterion was run using data from the
      Autism Diagnostic Interview-Revised (ADI-R) of N = 262 individuals exhibiting
      autism or autistic features. RESULTS: A three-factor solution consisting of two
      socio-communicative and one language dimension and accounting for 46.1% of the
      total variance was found to best describe the data. These factors yielded only
      vague correspondence with the idea of behavior domains described in ICD-10 and
      DSM-IV. In addition, factor loadings of items representing repetitive,
      stereotyped patterns were generally weak. CONCLUSIONS: The factor-analytic
      approach to autism indicates a conception of the disorder divergent from that
      defined in the contemporary psychiatric classification systems, especially
      regarding the area of repetitive, stereotyped behavior.

PMID- 11524899
TI  - [Initial experiences with amisulpride, an in Germany novel, atypical neuroleptic
      drug in treatment of adolescents with psychiatric disorders].
AB  - OBJECTIVES: In addition to conventional antipsychotic drugs, during the past
      decade an increasing number of atypical neuroleptics has been introduced in the
      treatment of juvenile schizophrenic and schizoaffective disorders. In 1999
      Germany legalized the benzamide amisulpride for the treatment of acute and
      chronic schizophrenic symptoms. Preliminary treatment results are reported here.
      METHODS: Ten adolescent cases are presented with regard to the efficacy, side
      effects and dosage of amisulpride. RESULTS: Preliminary results on the use of
      amisulpride are promising. The rate of side effects is tolerable. CONCLUSIONS:
      Amisulprise seems to constitute a useful alternative in the treatment of juvenile
      schizophrenia for those who suffer from intolerable side effects of classical or
      atypical neuroleptics. Controlled studies are warranted to further clarify its
      efficacy and safety in the treatment of adolescents.

PMID- 11524900
TI  - [Somatotype-specific anthropometry and eating disorders].

PMID- 11524901
TI  - Improve ars vivendi et moriendi!

PMID- 11524902
TI  - Recreational scuba diving, patent foramen ovale and their associated risks.
AB  - Scuba diving has become a popular leisure time activity with distinct risks to
      health owing to its physical characteristics. Knowledge of the behaviour of any
      mixture of breathable gases under increased ambient pressure is crucial for safe
      diving and gives clues as to the pathophysiology of compression or decompression
      related disorders. Immersion in cold water augments cardiac pre- and afterload
      due to an increase of intrathoracic blood volume and peripheral vasoconstriction.
      In very rare cases, the vasoconstrictor response can lead to pulmonary oedema.
      Immersion of the face in cold water is associated with bradycardia mediated by
      increased vagal tone. In icy water, the bradycardia can be so pronounced, that
      syncope results. For recreational dives, compressed air (i.e., 4 parts nitrogen
      and 1 part oxygen) is the preferred breathing gas. Its use is limited for diving
      to 40 to 50 m, otherwise nitrogen narcosis ("rapture of the deep") reduces a
      diver's cognitive function and increases the risk of inadequate reactions. At
      depths of 60 to 70 m oxygen toxicity impairs respiration and at higher partial
      pressures also functioning of the central nervous system. The use of special
      nitrogen-oxygen mixtures ("nitrox", 60% nitrogen and 40% oxygen as the typical
      example) decreases the probability of nitrogen narcosis and probably bubble
      formation, at the cost of increased risk of oxygen toxicity. Most of the health
      hazards during dives are consequences of changes in gas volume and formation of
      gas bubbles due to reduction of ambient pressure during a diver's ascent. The
      term barotrauma encompasses disorders related to over expansion of gas filled
      body cavities (mainly the lung and the inner ear). Decompression sickness results
      from the growth of gas nuclei in predominantly fatty tissue. Arterial gas
      embolism describes the penetration of such gas bubbles into the systemic
      circulation, either due to pulmonary barotrauma, transpulmonary passage after
      massive bubble formation ("chokes") or cardiac shunting. In recreational divers,
      neurological decompression events comprise 80% of reported cases of major
      decompression problems, most of the time due to pathological effects of
      intravascular bubbles. In divers with a history of major neurological
      decompression symptoms without evident cause, transoesophageal echocardiography
      must be performed to exclude a patent foramen ovale. If a cardiac right-to-left
      shunt is present, we advise divers with a history of severe decompression illness
      to stop diving. If they refuse to do so, it is crucial that they change their
      diving habits, minimising the amount of nitrogen load on the tissue. There is
      ongoing debate about the long term risk of scuba diving. Neuro-imaging studies
      revealed an increased frequency of ischaemic brain lesions in divers, which do
      not correlate well with subtle functional neurological deficits in experienced
      divers. In the light of the high prevalence of venous gas bubbles even after
      dives in shallow water and the presence of a cardiac right-to-left shunt in a
      quarter of the population (i.e., patent foramen ovale), arterialisation of gas
      bubbles might be more frequent than usually presumed.

PMID- 11524903
TI  - Assisted suicide as conducted by a "Right-to-Die"-society in Switzerland: a
      descriptive analysis of 43 consecutive cases.
AB  - BACKGROUND AND METHODS: The Swiss "Right-to-Die"-society EXIT enables assisted
      suicide by providing terminally ill members with a lethal dosage of barbiturates
      on request. This practice is tolerated by Swiss legislation. EXIT insists on its
      assumption that people with serious illness and suffering have the competency to
      take such a decision. The case of two patients who committed suicide a short time
      after their release from a psychiatric clinic raised some doubts about the
      practice of EXIT. The files of all 43 cases of suicide assisted by EXIT between
      1992 and 1997 in the region of Basle kept in the Institute of Forensic Medicine
      were examined for accuracy of the medical data. This sample was compared for age,
      gender-ratio and prior psychiatric treatment with 425 ordinary suicides in the
      same region. An attempt was made to assess whether only terminally ill and people
      with intolerable suffering had been assisted with suicide and what efforts EXIT
      had made to rule out psychiatric illnesses or poor social conditions as the
      reason for the wish to die. RESULTS: A medical report of the treating doctor(s)
      was in the files in only five cases. The "EXIT" cases where older than the
      "ordinary"-sample. Among those over 65 years old there were almost twice as many
      women as men. 16 of the 24 women older than 65 years were widowed. There were 20
      cases of cancer; but in eleven cases medical files revealed no apparent medical
      condition to explain a death-wish. Five of the patients declared a social loss or
      fear of such loss as the reason for their wish to die. Six persons had formerly
      been in psychiatric care, though this was not mentioned in the files.
      CONCLUSIONS: Due to the scarcity of information in the files as regards previous
      palliative care, the high proportion of old women and the high percentage of
      people not suffering from a terminal illness compared to the literature we
      conclude that psychiatric or social factors are not an obstacle for EXIT to
      assist with suicide.

PMID- 11524904
TI  - 10 Swiss kindreds with multiple endocrine neoplasia type 1: assessment of
      screening methods.
AB  - PRINCIPLES: Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant
      disease characterised by the combined occurrence of tumours of the parathyroid
      glands, the enteropancreatic neuroendocrine system and the anterior pituitary
      gland. The genetic defect has been mapped to the long arm of chromosome 11q13,
      and the MEN1-gene was recently identified by positional cloning. Genetic
      screening for MEN1 germline mutations allows the identification of gene carriers
      in affected kindreds. Biochemical and radiological screening for MEN1 tumours
      allows an earlier diagnosis and treatment, and, thus may reduce morbidity and
      mortality. Since there is no consensus about the frequency and the extent of the
      necessary screening investigations, evaluation of proposed screening programs is
      of importance. METHODS: The aims of our study were to identify the MEN1-gene
      mutations and to detect the gene-carriers in 10 Swiss MEN1 families, as well as
      to assess biochemical and radiological screening methods. The study included 45
      members from 10 MEN1 families. RESULTS: Every family had a different type of MEN1
      gene mutation. Thirty out of 45 family members were gene mutation carriers.
      Twenty-two MEN1-gene carriers had typical MEN1 tumours: parathyroid,
      enteropancreatic and pituitary tumours were found in 21, 14 and 1 patients,
      respectively. Applying a defined screening program the following manifestations
      in asymptomatic MEN1-gene carriers were detected: 9 primary hyperparathyroidism,
      3 nonfunctioning pancreatic tumours, 1 gastrinoma, 1 nonfunctioning microadenoma
      of the pituitary and 1 macronodular adrenal hyperplasia. CONCLUSIONS: The genetic
      screening facilitates the identification of individuals who carry MEN1-gene
      mutations, and allows one to exclude non-mutant gene carriers from further
      investigations. The prospective biochemical and radiological screening of gene
      mutation carriers allows the earlier detection of MEN1-associated tumours.
      Therefore, it might be expected that morbidity and mortality of the MEN1 could be
      reduced.

PMID- 11524905
TI  - Dexamethasone treatment of a patient with large bilateral chronic subdural
      haematomata.

PMID- 11524906
TI  - Medical-ethical principles on xenotransplantation.

PMID- 11524907
TI  - [Non-occidental cultural concepts and pediatrics: thoughts on the meeting of
      different worlds].

PMID- 11524908
TI  - [Cardiac rhythm disturbances and prolonged QT interval with halofantrine].
AB  - OBJECTIVE: To determine the importance of prolonged QT interval and
      electrocardiographic changes in children treated with halofantrin for an acute
      malaria attack. RESULTS: Out of 25 children treated with halofantrin, nine had an
      increase of QTc interval < 440 ms and ten a QTc > 440 ms on control 24 h after
      the first dose. A 9-year-old girl, treated with halofantrin, had bradycardia and
      increase of QTc interval for six days, with a normal halofantrin blood level.
      CONCLUSION: These data show that cardiac monitoring during halofantrin treatment
      is mandatory in children as in adults. Contraindications of halofantrin treatment
      must be respected, particularly a long congenital QT interval.

PMID- 11524909
TI  - [Bone marrow transplantation in Fanconi's anemia: report of seven cases].
AB  - OBJECTS: Follow-up of patients with Fanconi's anemia treated in our unit and
      review of the literature concerning bone marrow transplantation in Fanconi's
      anemia. PATIENTS AND METHODS: Ten patients were followed in our unit for 20
      years. We summarize their clinical features, treatment and clinical course.
      RESULTS: Among the ten patients, seven received allogeneic marrow
      transplantation. Only two patients are still alive. Two transplanted patients
      died from complications shortly after the transplantation. Three other patients
      died later after the transplantation, two of them from oropharyngeal carcinomas.
      DISCUSSION: The 5-year survival is about 70% in the transplantation with an HLA
      identical sibling donor; it is only about 30% if the donor is an HLA-matched
      unrelated or mismatched related patient. Furthermore, retrospective studies have
      shown that the long-term outcome of carcinoma is a major complication after the
      transplantation. CONCLUSION: Our series of patients with Fanconi's anemia
      reflects fairly faithfully the complications encountered in this disease.
      Although the improvement of the graft technique may decrease the rate of death
      due to transplantation, the long-term development of solid tumors remains a
      problem for which no solution has been suggested up to now.

PMID- 11524910
TI  - [Initiation and duration of breastfeeding in obstetrical hospitals of Aix
      Chambery (France)].
AB  - Our objectives were to estimate duration of breastfeeding and to identify factors
      associated with initiation and weaning. METHODS: A prospective study was carried
      out among 353 mothers delivering in three obstetric hospitals at Aix-Chambery
      (Savoie, France). Breastfeeding was considered as survival data with censored
      observations. Univariate and multivariate analyses were performed. RESULTS:
      Breastfeeding was initiated by 70.8% (66.1-75.5) (exclusive breastfeeding = 39.9%
      and complementary breastfeeding = 30.9%). Respectively, 58.1% (52.9-63.3) and
      12.2% (8.3-16.1) were continuing some breastfeeding at one and six months. The
      median duration of breastfeeding was 13 weeks (11.6-14.4). Shorter duration was
      associated with contact beyond one hour from birth (adjusted Hazard Ratio [aHR] =
      1.25 [1.03-1.52] and with contact beyond eight hours aHR = 1.78 [1.66-1.92]),
      pacifier use (aHR = 1.72 [1.19-2.47]), breastfeeding at fixed hours (aHR = 1.78
      [1.29-2.45]), and decision to breastfeed during pregnancy or the postpartum
      period (aHR = 1.70 [1.45-2.00]). CONCLUSION: Breastfeeding initiation and
      duration were higher in maternity hospitals of Chambery than estimations measured
      in the 1998 French perinatal survey and in other ad hoc surveys. Identified
      factors should be used in order to plan future programs designed to increase
      duration of breastfeeding.

PMID- 11524911
TI  - [27-gauge percutaneous catheters: use in nutritional management of very-low-birth
      weight and severely premature newborns in a neonatal intensive care unit].
AB  - Percutaneous central venous catheterization for parenteral feeding is a permanent
      problem in the management of very low birth weight neonates. Usually, 23-gauge
      catheters (diameter: 0.6 mm) are used. In our unit, we have started to use 27
      gauge catheters (diameter 0.35 mm) since 1995. The aim of this study was to
      report our experience with this materiel. SUBJECT AND METHODS: Between September
      1, 1997 and January 30, 2000, 352 catheter implantations were performed using 27
      gauge infusing sets in 200 premature infants (gestational age less than or equal
      to 33 weeks [mean 29.2], weight less than or equal to 1,500 g [mean: 1, 152.5
      g]). Data were reviewed retrospectively with the view to determine the modality
      of use and complications. Peculiar insertion modalities were prospectively
      evaluated in the 50 last included infants (92 catheters). RESULTS: In 97% of
      cases, the physician needed no help to insert the catheter. In 99.5% of cases
      (199 neonates), the insertion was successful (the procedure failed in one case).
      The mean duration procedure was 26 min (range 10 to 85 min). The mean age at
      insertion of the first catheter was 29 hours (range 0 to 216). Mean catheter
      maintenance duration was 15 days (range 1 to 53). In 31 cases, documented sepsis
      related to the catheter were noted (8.8% or 5.8 infections for 1,000 catheter
      days). Endocarditis was observed in one case. A pericardial effusion was
      diagnosed in two cases. No death related to the catheter was noted. CONCLUSION:
      In our experience, 27-gauge catheter implantation is an easy and safe procedure.
      We noted no major maintenance problems. Complications were not observed more
      frequently than those usually encountered with 23-gauge catheters. We conclude
      that 27-gauge catheter utilization is an attractive alternative for percutaneous
      central venous catheterization, in very low birth weight neonates.

PMID- 11524912
TI  - [Neonatal nonbacterial thrombotic endocarditis].
AB  - Nonbacterial thrombotic endocarditis is not widely known in neonates. CASE
      REPORTS: We report three new cases which illustrate some specific aspects of this
      pathology. Respiratory distress with severe pulmonary hypertension, systemic
      hypotension and disseminated intravascular coagulopathy in a full-term newborn
      were characteristic findings. CONCLUSION: An early echocardiography should lead
      to accurate diagnosis. Hypoxemia and genetic factors could be determining factors
      in its pathogenesis.

PMID- 11524913
TI  - [Epidural hematoma in a child with hemophilia: diagnostic difficulties].
AB  - Spinal epidural hematoma is an uncommon complication in hemophilia. CASE REPORTS:
      The cases of an extensive epidural hematoma in two boys with severe hemophilia
      are reported. CONCLUSION: Acute onset of severe neck pain or backache leads to
      the diagnosis of epidural hematoma in children with hemophilia, even in the
      absence of neurologic symptoms. Early diagnosis is important and relies on
      magnetic resonance imaging. Replacement therapy is mandatory and must be
      prescribed before neuroradiologic imaging. Generally, children have a good
      neurologic outcome.

PMID- 11524914
TI  - [Osteoarticular brucellosis and signs of autoimmunity].
AB  - We report two cases of osteoarticular brucellosis in childhood, which illustrate
      the diagnostic difficulties in non-endemic areas. CASE REPORT: A 12-year-old boy
      was admitted for a unilateral sacroiliitis for which the brucellosis origin was
      established by serological and blood cultures (without fever). Autoimmunity was
      detected and disappeared following the treatment of the affection. A six-year-old
      girl was admitted for a monoarthritis of the left ankle (with fever) for which
      the brucellosis origin was also established by serology and blood cultures.
      COMMENTS: The above cases underline the importance of knowing the atypical
      varieties of brucellosis. The brucellosis serologies need to take part in the
      etiological workup of an infectious osteoarthritis when a classic infectious
      cause cannot be proved. Blood cultures on a specific medium are essential to
      carry out, even in the case of apyrexia. Finally, the possibility of autoimmunity
      signs for the brucellosis has to be known to avoid orientating the diagnosis
      towards an autoimmune systemic disease.

PMID- 11524915
TI  - [Dyggve-Melchior-Clausen syndrome: differential diagnosis of
      mucopolysaccharidosis type IV or Morquio disease].
AB  - Dyggve-Melchior-Clausen syndrome (DMCS) is an autosomal recessive skeletal
      dysplasia. Clinical and radiological similarities with Morquio's syndrome can
      initially lead wrongly to this diagnosis. CASE REPORT: A nine-year-old boy had
      mental retardation and progressive postnatal dwarfism. Platyspondyly and
      dysplastic epiphyses and metaphyses resembled those of Morquio's disease;
      however, clinical and radiological data led to the diagnosis of DMCS. CONCLUSION:
      Clinical and paraclinical features allowing the differentiation of Morquio's
      syndrome and DMCS are discussed. Initial clinical presentation may be similar,
      but the intellectual prognosis is different.

PMID- 11524916
TI  - [Meningococcal purpura fulminans: untoward result of genetic polymorphism?].
AB  - Despite significant progress in intensive care medicine, the mortality of septic
      shock has not changed in recent years. Early recognition of subtle signs in favor
      of meningococcal sepsis, early antibiotic treatment, and aggressive hemodynamic
      support remains the cornerstone of therapy of severe meningococcal shock in
      children. Recent work has emphasized the role of genetic polymorphisms in various
      systems to explain the most severe cases: anti-inflammatory cytokine profile IL
      10/TNF-alpha, elevated levels of plasminogen activator inhibitor type-1, variants
      of the gene for mannose-binding lectin complement pathway. This may explain the
      disillusionment of pediatric intensivists, and the general failure of
      immunotherapy for sepsis. Reasonable hope lies upon new meningococcal vaccines.

PMID- 11524917
TI  - [Fanconi's anemia and molecular biology research].
AB  - Fanconi's anemia is a rare autosomal recessive disease characterized by
      congenital abnormalities, a progressive pancytopenia and a predisposition to
      cancer. The diagnosis is based on an abnormal increase of spontaneous chromosome
      breakage, more specifically on a clear-cut increase of chromosome breakage in the
      presence of bifunctional alkylating agents. Eight complementation groups (A to H)
      have been defined, and the genes corresponding to four of these groups have been
      cloned (FANCA, FANCC, FANCF and FANCG). The function of the proteins encoded by
      the genes of Fanconi's anemia remains unknown. Numerous studies indicate that
      different cellular processes are probably involved, including DNA repair
      pathways, apoptosis, cell cycle regulation and oxygen metabolism. Nevertheless,
      the exact cellular and molecular mechanisms implicated in Fanconi's anemia remain
      a challenge for fundamental research. The treatment of Fanconi's anemia is also
      the subject of intense research, bearing principally upon bone marrow
      transplantation, which is successful in the case of HLA-identical sibling donors,
      and gene therapy, which is still at a preliminary stage on the clinical level.

PMID- 11524918
TI  - [Radiographic case of the month. Intermittent volvulus with intestinal
      malrotation diagnosed prenatally].

PMID- 11524919
TI  - [Document for the promotion of breast feeding].
AB  - Despite its many advantages, breastfeeding is poorly developed in France: less
      than 50% of newborns are breastfed, and only 10% of infants continue to be
      breastfed at 1 month of age. In order to encourage breastfeeding in the French
      North department (chief town: Lille), a working group has written a document for
      promoting breastfeeding. The reasons for breastfeeding disaffection in France are
      analysed. The nutritional, health, psychological, economic and social advantages
      of breastfeeding are presented, together with the fact that breastfeeding has to
      be considered as part of the human rights for mothers and children. The actions
      to take place to develop breastfeeding are presented.

PMID- 11524920
TI  - [Negative effects of maternal smoking during the course of pregnancy].
AB  - Maternal smoking during pregnancy has many consequences, manifesting prior to,
      during and after pregnancy, mainly: fertility difficulties; obstetrical accidents
      such as extrauterine pregnancy, premature labour and early placenta detachment;
      intrauterine growth retardation; increased perinatal morbidity; increased
      susceptibility to respiratory diseases in infancy and childhood; increased rate
      of sudden infant death; and alteration of cognitive development and behavioral
      disorder in childhood. Postnatal smoke exposure increases the respiratory
      complications in infancy and childhood. Considering the severity of these
      deleterious effects, the development of a large preventive policy appears
      necessary.

PMID- 11524921
TI  - [Role of bodily practices with newborn in the development of cultural identity.
      Examples of bodily practices in Africa and India].
AB  - Bodily practices on newborns are the indicators of communication between the
      child and his/her surroundings. The culture has to introduce individuals into a
      specific group by using particular practices that have applied to the past
      generations. The techniques are different according to the ethnic group and allow
      the child to reach a social birth. To emphasize the relation between the identity
      and the culture, four cultural examples are presented. In Bambara country, the
      grandmothers massage and stretch the newborn in order to let him feel the limits
      of his body and get into the Bambara identity. For the Wolof, the psychomotor
      development will be made with specific movements on the body of the child
      according to initiation rituals. In Kabylie, the child will be protected from the
      outside world before he gets his proper name. In Tamil country, the way the
      foetus and the child are helped emphasize his coming into the living world and
      his reincarnated identity. The psychic structuring and the culture are tightly
      connected and the body is the first mediator of that representation.

PMID- 11524922
TI  - [Thrombocytosis and cholestasis in a newborn treated with zidovudine].

PMID- 11524923
TI  - [Guillain-Barre syndrome following immunization against Haemophilus influenzae
      type b].

PMID- 11524924
TI  - [Early neonatal encephalopathy in the full-term newborn: a disease that remains
      with us. The experience of a pediatric intensive care service].

PMID- 11524925
TI  - [An adolescent vegetarian].

PMID- 11524926
TI  - What's your greatest risk?

PMID- 11524927
TI  - Why are our baby doctors disappearing?

PMID- 11524928
TI  - Sidestepping osteoporosis.

PMID- 11524929
TI  - Nutritional supplements: to munch or not to munch?

PMID- 11524930
TI  - Dealing with menopause the natural way.

PMID- 11524931
TI  - Let's safeguard the health of Pennsylvania's women.

PMID- 11524933
TI  - Pennsylvania caregivers have help.

PMID- 11524934
TI  - Success in liver transplantation.

PMID- 11524935
TI  - A 14-year old with a discharge after sex.

PMID- 11524936
TI  - Recent developments in hepatology.

PMID- 11524937
TI  - Managing gallstones.

PMID- 11524938
TI  - Casebook: jaundice.

PMID- 11524939
TI  - Hepatobiliary tumours.

PMID- 11524941
TI  - An Rx for Russia: more kids, less booze.

PMID- 11524942
TI  - [Aleksandr Sergeevich Spirin (70th anniversary of his birth)].

PMID- 11524943
TI  - [Major mRNP proteins in the structural organization and function of mRNA in
      eukaryotic cells].
AB  - The properties of two universal major proteins of cytoplasmic mRNP, p50 and the
      poly(A)-binding protein (PABP), are summarized. Their roles in formation of
      polyribosomal and free inactive mRNP are considered, with the focus on the
      authors' studies of p50. The parts these mRNP proteins play in translation
      regulation, stability, and localization of mRNA are described, and the the
      possible mechanisms of their function are discussed.

PMID- 11524944
TI  - [Study of ribosome structure using the biochemical methods: judgment day].
AB  - The data on RNA-RNA interactions between the components of the E. coli
      translation machinery obtained by X-ray crystallography and chemical methods are
      compared. The approaches to the study of RNA secondary and tertiary structure are
      assessed. The following conclusions are made: comparative sequence analysis and
      compensatory mutations approach both give reliable data on the RNA secondary
      structure. The chemical modification technique provides good results. Local
      cleavage of internucleotide bonds by hydroxyl radicals is reliable in the frame
      of its 40 A resolution, in contrast to the application of copper-phenanthroline
      complex as a cleavage reagent, which is unreliable. Direct UV irradiation and
      nitrogen mustard treatment are the best methods of crosslink generation. In vitro
      transcription is the only good method for the incorporation of nucleotide analogs
      in RNA. RNase H hydrolysis and/or nucleotide-specific RNases fingerprints must be
      applied for the crosslink site determination in parallel with reverse
      transcription.

PMID- 11524945
TI  - [Structural-functional topography of human ribosomes based on the data from
      crosslinking with mRNA analogs--oligoribonucleotide derivatives].
AB  - Reviewed are data on the position of template codons with respect to 18S rRNA and
      certain proteins on human ribosome obtained using a set of mRNA analogs,
      oligoribonucleotide derivatives carrying alkylating or photoactivatable group at
      different positions. A comparison of data on template position on the human and
      Escherichia coli ribosomes has revealed both the similarity in the structure of
      the mRNA-binding site of bacterial and mammalian ribosomes and the peculiarities
      of the functioning of mammalian (in particular, human) ribosomes. The similarity
      manifests itself in that the template codons at the A, P, and E sites of
      bacterial and human ribosomes are surrounded by similar nucleotides (occupying
      similar positions in the conserved regions of secondary structure) of small
      subunit rRNA. The template forms a loop whose foot is in proximity to the 530
      stem-loop conserved region of rRNA. The specific features of mammalian ribosomes
      appear to be associated with their lower conformational mobility as compared with
      bacterial ribosomes, owing to which their interaction with the template involves
      a lesser number of molecular contacts.

PMID- 11524946
TI  - [Ribosomal antibiotics].
AB  - In spite of decades of research, our understanding of the principles of
      antibiotic binding to the ribosome and the mechanisms of drug action remains only
      fragmentary. Recent progress in biochemical and genetic studies of some "old" and
      new antibiotics and the availability of high-resolution structures of the
      ribosome subunits allows mapping the antibiotic-binding sites at atomic
      resolution. In this review, interaction of three groups of antibiotics with the
      ribosome and the mechanisms of the drug action are discussed, considering the
      data used to map the binding sites of the new macrolide derivatives, ketolides, a
      novel clinically important antibiotic linezolid, and a still experimental drug
      evernimicin.

PMID- 11524947
TI  - [The Thermus thermophilus 5S rRNA-protein complex: Identifications of specific
      binding sites for proteins L5 and L18 in 5S rRNA].
AB  - Three 5S rRNA-binding ribosomal proteins (L5, L18, TL5) of extremely thermophilic
      bacterium Thermus thermophilus have earlier been isolated. Structural analysis of
      their complexes with rRNA requires identification of their binding sites in the
      5S rRNA. Previously, a TL5-binding site has been identified, a TL5-RNA complex
      crystallized, and its structure determined to 2.3 A. The sites for L5 and L18
      were characterized, and two corresponding 5S rRNA fragments constructed. Of
      these, a 34-nt fragment specifically interacted with L5, and a 55-nt fragment
      interacted with L5, L18, and with both proteins. The 34-nt fragment-L5 complex
      was crystallized; the crystals are suitable for high-resolution X-ray analysis.

PMID- 11524948
TI  - [Study of the binding of the S7 protein with 16S rRNA fragment 926-986/1219-1393
      as a key step in the assembly of the small subunit of prokaryotic ribosomes].
AB  - Both structural and thermodynamic studies are necessary to understand the
      ribosome assembly. An initial step was made in studying the interaction between a
      16S rRNA fragment and S7, a key protein in assembling the prokaryotic ribosome
      small subunit. The apparent dissociation constant was obtained for complexes of
      recombinant Escherichia coli and Thermus thermophilus S7 with a fragment of the
      3' domain of the E. coli 16S rRNA. Both proteins showed a high rRNA-binding
      activity, which was not observed earlier. Since RNA and proteins are
      conformationally labile, their folding must be considered to correctly describe
      the RNA-protein interactions.

PMID- 11524949
TI  - [Study of molecular mechanisms of translation initiation in mammals using in
      vitro reconstruction of initiation complexes].
AB  - Papers on the mechanisms of translation initiation in mammals studied by
      reconstruction of initiation complexes from individual components are reviewed.
      The author points to the constraints of this approach and to the pitfalls
      ignoring which one might come to erroneous conclusions and even artifacts. In
      addition, some methods employed in the field as well as some technical problems
      are discussed in the paper, together with the means of obviating them. The review
      could be a guidebook for newcomers into this quite labor-consuming field.

PMID- 11524950
TI  - [Translation initiation factor eIF3 is able to bind with microtubules in
      mammalian cells].
AB  - Association of the translation apparatus with the cytoskeleton is essential for
      its transportation within the cell and probably also for translation regulation.
      Very little is known about the involvement of particular proteins of this
      association. A polypeptide homologous with the heavy chain of translation
      initiation factor eIF3 p170 was found earlier in a microtubule preparation from
      adrenal cells. Antibody A167 directed against the recombinant fragment of p170
      has been generated to study eIF3 interaction with microtubules in mammalian
      cells. This antibody was shown to recognize a single 170 kDa polypeptide in eIF3
      preparations as well as in homogenates of various cell types. A167 allowed
      detection of the 170 kDa polypeptide in microtubule preparation from bovine brain
      and confirmation of its presence in microtubule preparations from adrenal cells.
      As shown by immunofluorescence microscopy using A167, the 170 kDa polypeptide is
      mainly located in the endoplasm within numerous small and some large granules.
      Cell treatment with cycloheximide resulted in growth and clustering of the large
      granules, and partial antigen redistribution along cellular microtubules. These
      new experimental data indicate that mammalian translation factor eIF3 may bind
      with microtubules.

PMID- 11524951
TI  - [Structure and functions of the prokaryotic elongation factor G].
AB  - Structural and functional data on elongation factor G (EF-G) are reviewed with
      regard to nucleotide exchange, GTP hydrolysis, mechanism of action of fusidic
      acid, and functional roles of the EF-G structural domains in translocation.
      Biochemical data are correlated with structural dynamics of the EF-G molecule on
      interaction with various ligands. Data on EF-Tu are also considered, as EF-G and
      EF-Tu share certain structural and functional features.

PMID- 11524952
TI  - [Mechanism of tRNA translocation on the ribosome].
AB  - During the translocation step of the elongation cycle of peptide synthesis two
      tRNAs together with the mRNA move synchronously and rapidly on the ribosome.
      Translocation is catalyzed by the elongation factor G (EF-G) and requires GTP
      hydrolysis. The fundamental biochemical features of the process were worked out
      in the 1970-80s, to a large part by A.S. Spirin and his colleagues. Recent
      results from pre-steady-state kinetic analysis and cryoelectron microscopy
      suggest that translocation is a multistep dynamic process that entails large
      scale structural rearrangements of both ribosome and EF-G. Kinetic and
      thermodynamic data, together with the structural information on the
      conformational changes of the ribosome and of EF-G, provide a detailed
      mechanistic model of translocation and suggest a mechanism of translocation
      catalysis by EF-G.

PMID- 11524953
TI  - [Mutations in the Escherichia coli 23S rRNA increase the rate of peptidyl-tRNA
      dissociation from the ribosome].
AB  - We have studied in vivo the phenotypes of 23S rRNA mutations G2582A, G2582U,
      G2583C, and U2584C, which are located at the A site of Escherichia coli 50S
      ribosomal subunit. All mutant rRNAs incorporated into 50S ribosomal subunits.
      Upon sucrose gradient fraction of cell lysates, 23S rRNAs mutated at G2582 to A
      and G2583 to C accumulated in the 50S and 70S fractions and were under
      represented in the polysome fraction. Induction of 23S rRNAs mutated at G2582 and
      G2583 lead to a drastic reduction in cell growth. In addition, mutations G2582A
      and G2583C reduced to one-third the total protein synthesis but not the RNA
      synthesis. Finally, we show that 23S rRNA mutations G2582A, G2582U, and G2583C
      cause a significant increase in peptidyl-tRNA drop-off from ribosomes, thereby
      reducing translational processivity. The results clearly show that tRNA-23S rRNA
      interaction has an essential role in maintaining the processivity of translation.

PMID- 11524954
TI  - [Identification of a novel termination release factor eRF3b expressing the eRF3
      activity in vitro and in vivo].
AB  - Termination of translation in eukaryotes is governed by the ribosome, a
      termination codon in the mRNA, and two polypeptide chain release factors (eRF1
      and eRF3). We have identified a human protein of 628 amino acids, named eRF3b,
      which is highly homologous to the known human eRF3 henceforth named eRF3a. At the
      nucleotide and at the amino acid levels the human eRF3a and eRF3b are about 87%
      identical. The differences in amino acid sequence are concentrated near the amino
      terminus. The most important difference in the nucleotide sequence is that eRF3b
      lacks a GGC repeat close to the initiation codon in eRF3a. We have cloned the
      cDNA encoding the human eRF3b, purified the eRF3b expressed in Escherichia coli,
      and found that the protein is active in vitro as a potent stimulator of the
      release factor activity of human eRFl. Like eRF3a, eRF3b exhibits GTPase
      activity, which is ribosome- and eRFl-dependent. In vivo assays (based on
      suppression of readthrough induced by three species of suppressor tRNAs: amber,
      ochre, and opal) show that the human eRF3b is able to enhance the release factor
      activity of endogenous and overexpressed eRFl with all three stop codons.

PMID- 11524955
TI  - [Cotranslational protein folding].
AB  - The review analyzes the research concerning the folding of proteins in the course
      of their synthesis on ribosomes. The experimental data obtained for various
      proteins using various methods give grounds for concluding that a nascent protein
      largely acquires its spatial structure while still attached to the ribosome, and
      final folding into the biologically active conformation takes place as soon as
      the completed protein is released therefrom. Cotranslational folding is
      characteristic of both bacterial and eukaryotic cells, and appears to be the
      universal and the most evolutionarily ancient mechanism.

PMID- 11524956
TI  - [Translational control of the picornavirus phenotype].
AB  - Picornaviruses are small animal viruses with positive-stranded genomic RNA, which
      is translated using cap-independent internal translation initiation. The key role
      in this is played by cis elements of the 5'-untranslated region (5'-UTR) and, in
      particular, by the internal ribosome entry site (IRES). The function of
      translational cis elements requires both canonical translation initiation factors
      (eIFs) and additional IRES trans-acting factors (ITAFs). All known ITAFs are cell
      RNA-binding proteins which play a variety of functions in noninfected cells.
      Specific features of translational cis elements substantially affect the
      phenotype and, in particular, tissue tropism and pathogenic properties of
      picornaviruses. It is clear that, in some cases, the molecular mechanism of this
      is a change in interactions between viral cis elements and ITAFs. The properties
      and tissue distribution of ITAFs may determine the biological properties of other
      viruses that also use the IRES-dependent translation initiation. Since this
      mechanism is also involved in translation of several cell mRNAs, ITAF may
      contribute to the regulation of the most important aspects of the living activity
      in noninfected cells.

PMID- 11524957
TI  - [Functional compartmentation of the translation apparatus and channeling of
      tRNA/aminoacyl-tRNA in cells of higher eukaryotes].
AB  - Literature data and authors' results in the field of structure-function
      organization of the translation apparatus in higher eukaryotes are considered.
      Proof is presented of the channeling of tRNA/aminoacyl-tRNA in the course of
      eukaryotic protein synthesis. The concept of the shuttle role of elongation
      factor eEF1A is grounded; the factor, being in a GTP-bound form, delivers
      aminoacyl-tRNA to the ribosome and then, in the GDP form after hydrolysis of GTP
      on the ribosome, forms a complex with the deacylated tRNA and delivers it to the
      aminoacyl-tRNA synthetase. The notion of translational compartment is defined.

PMID- 11524958
TI  - [Kinetics of folding nuclei formation in proteins].
AB  - When a protein folds or unfolds, it passes through many half-folded microstates.
      Only a few of them can accumulate and be seen experimentally, and this happens
      only when the folding (or unfolding) occurs far from the point of thermodynamic
      equilibrium between the native and denatured states. The universal features of
      folding, though, are observed in the vicinity of the equilibrium point. Here the
      "two-state" transition proceeds without any accumulation of metastable
      intermediates, and only the transition state ("folding nucleus") is outlined by
      its key influence on the folding/unfolding kinetics. This review covers recent
      experimental and theoretical studies of folding nuclei.

PMID- 11524959
TI  - [Why termination tRNAs have not been found? Because they are hidden in the large
      ribosomal RNA].
AB  - It is well known that protein synthesis in ribosomes on mRNA requires two kinds
      of tRNAs: initiation and elongation. The former initiates the process
      (formylmethionine tRNA in prokaryotes and special methionine tRNA in eukaryotes).
      The latter participates in the synthesis proper, recognizing the sense codons.
      The synthesis is assisted by special proteins: initiation, elongation, and
      termination factors. The termination factors are necessary to recognize stop
      codons (UAG, UGA, and UAA) and to release the complete protein chain from the
      elongation tRNA preceding a stop codon. No termination tRNA capable of
      recognizing stop codons by its anticodon is known. The termination factors are
      thought to do this. We discovered in the large ribosomal RNA two regions that,
      like tRNAs, contain the anticodon hairpin, but with triplets complementary to
      stop codons. By analogy, we called them termination tRNAs (Ter-tRNA1 and Ter
      tRNA2), though they transport no amino acids, and suggested them to directly
      recognize stop codons. The termination factors only condition such a recognition,
      making it specific and reliable (of course, they fulfill the hydrolysis of the
      ester bond between the polypeptide and tRNA). A strong argument in favor of our
      hypothesis came from vertebrate mitochondria. They acquired two new stop codons,
      AGA and AGG (in the standard code, they are two out of six arginine codons). We
      revealed that the corresponding anticodons appear in Ter-tRNA1.

PMID- 11524960
TI  - [Ribosome and the secret of longevity].
AB  - Proteins in cells are constantly undergoing damage. Nevertheless, the
      concentration of damaged proteins in young organisms is maintained at the low
      level due to the continual protein turnover: degradation of damaged proteins and
      synthesis of new ones. During aging, the concentration of damaged proteins
      increases because of decelerating protein turnover, the cause of which is
      unknown, however, it may be related to the decrease in ribosome concentration.

PMID- 11524961
TI  - Cloning: where do you draw the line? The house vote to ban all human cloning was
      the first skirmish in the research wars to come. Next up: stem cells.

PMID- 11524962
TI  - Better than a nursing home?

PMID- 11524963
TI  - Absolutely fabulous? The TV ads promise easy rock-hard abdominals, but studies
      show there's no such thing as a free six-pack.

PMID- 11524964
TI  - Death by 100 degrees.

PMID- 11524966
TI  - Nano nonsense and cryonics.

PMID- 11524965
TI  - Cancer in the crosshairs.

PMID- 11524967
TI  - Little big science. Nanotechnology.

PMID- 11524968
TI  - The art of building small.

PMID- 11524969
TI  - Plenty of room, indeed.

PMID- 11524970
TI  - The incredible shrinking circuit.

PMID- 11524972
TI  - Machine-phase nanotechnology.

PMID- 11524971
TI  - Less is more in medicine.

PMID- 11524973
TI  - Of chemistry, love and nanobots.

PMID- 11524974
TI  - The once and future nanomachine.

PMID- 11524975
TI  - Nanobot construction crews.

PMID- 11524977
TI  - Flea treatments. Killer drops.

PMID- 11524978
TI  - [New approach in therapy refractory depression. Pacemaker for mood (interview by
      Dr. Brigitte Moreano)].

PMID- 11524979
TI  - ["Cleansing, topical treatment, oral administration". Controlling acne].

PMID- 11524980
TI  - [Respite for family caregivers of dementia patients. Nursing home admission can
      be delayed].

PMID- 11524981
TI  - [Important acute measures after fractures. Rapid and adequate treatment of pain].
AB  - Pain caused by bone fractures needs to be treated promptly and adequately to
      avoid negative secondary effects. Pain therapy and the healing of soft tissue are
      goals that are equally as important as healing of the fracture. The following
      factors have analgesic potential: reduction, immobilization, cooling measures,
      limb elevation and fasciotomy. Symptomatic treatment of pain is orientated to the
      WHO stepped approach, which attaches particular importance to the regular
      administration of analgesics, as dictated by clinical effectiveness.

PMID- 11524982
TI  - [When fracture pain does not subside. Recognizing complications].
AB  - Over the long term, the evolution of pain caused by fractures is determined by
      the quality of immobilization, the extent of edema, and by surgical, analgesic
      and physiotherapeutic treatment. Development of chronicity is initiated by
      secondary deterioration, persistence of pain in the absence of improvement,
      changes in the nature of the pain, its spontaneous occurrence, and the appearance
      of concomitant symptoms. Differential diagnostic considerations must include
      surgical complications, but also damage to nerves, or the complex regional pain
      syndrome (CRPS). A particular differential diagnostic problem is the
      differentiation between CRPS and other complications. Treatment must be matched
      to the diagnosis: conservative attempts at treatment may have to be followed up
      with surgical revision. Drug treatment of pain is oriented to the stepped WHO
      schema. Physiotherapy, physical treatment and ergotherapy play a major role in
      the treatment of CRPS.

PMID- 11524984
TI  - [Tumor therapy in the elderly--is it possible? Plea for an individual treatment
      concept].

PMID- 11524983
TI  - [Modern methods of insulin administration. Jet injection--end of "injection
      anxiety"?].

PMID- 11524985
TI  - [The suicidal patient. Take every suggestion seriously!].

PMID- 11524986
TI  - [Integration and disease management. Contracts with or without national health
      insurance?].

PMID- 11524987
TI  - [Bisphosphonates once weekly. Osteoporosis therapy becomes more effective].

PMID- 11524988
TI  - [Prostate problems. More clarity regarding prognosis].

PMID- 11524989
TI  - [New quinolone. Better effectiveness in problem cases].

PMID- 11524990
TI  - [Activated arthrosis. Nettle extract against inflammation].

PMID- 11524991
TI  - [Diabetes and hypertension. HYDRA study to uncover management and therapy
      problems].

PMID- 11524992
TI  - [Urticaria. Finally undisturbed sleep].

PMID- 11524993
TI  - [Bronchial asthma. Patient management still has deficits].

PMID- 11524994
TI  - [ACE inhibitor plus glitazone. Insulin sensitizer, preventing diabetes?].

PMID- 11524995
TI  - [Cultural and medical history of snoring. How to fell trees during sleep].

PMID- 11524996
TI  - Preventing secondary meningococcal disease in health care workers:
      recommendations of a working group of the PHLS meningococcus forum.
AB  - Based on new data on the risk of secondary meningococcal disease in health care
      workers, a review of published cases and an assessment of the available evidence,
      a change to the recommendations for giving chemoprophylaxis to health care
      workers in England and Wales is proposed. Previous guidance recommended
      prophylaxis only for those who had given mouth to mouth resuscitation.
      Chemoprophylaxis is now recommended for health care workers whose mouth or nose
      has been directly and heavily exposed to respiratory droplets/secretions from a
      case of meningococcal disease around the time of hospital admission. Wearing
      surgical face masks is encouraged to reduce risk of exposure.

PMID- 11524997
TI  - The prevention of tetanus in England and Wales.
AB  - Today, tetanus is a rare disease in England and Wales although in less developed
      and less affluent areas of the World it is still a major cause of morbidity and
      mortality, particularly in neonates and women following childbirth. An estimated
      400,000 deaths worldwide occur annually from neonatal tetanus and in 1989 the
      World Health Organization adopted the goal of eliminating neonatal tetanus as a
      public health problem by 1995-2000. This goal has not yet been achieved
      worldwide; however in England and Wales tetanus in neonates and young women has
      been extremely rare for the last 50 years. We can attribute the success in
      eliminating tetanus in the UK to the adoption of highly effective preventative
      measures as we know that the causative organism is still ubiquitous in the
      environment. This article outlines how we have achieved the elimination of
      tetanus in the UK through the development and introduction of appropriately
      targeted immunisation, combined with an appreciation of the importance of
      adequate wound toilet measures. The discovery of tetanus toxoid and its
      applicability for vaccination has been of great benefit and the new challenges
      which we face relate to the introduction of new multi-component vaccines and how
      we might better protect the elderly. In other parts of the world, for the cost of
      a few pence, one dose of tetanus toxoid can still mean the difference between
      life and death.

PMID- 11524998
TI  - Burkholderia cepacia and cystic fibrosis--50 years on.
AB  - Burkholderia cepacia (also known as Pseudomonas cepacia or P. multivorans), is a
      complex of bacteria that are phylogenetically distinguishable from each other but
      phenotypically indistinguishable. Though already present in the environment, they
      have been given selective advantage by changing environments and now infect a new
      and susceptible host group--cystic fibrosis sufferers. This brief review
      highlights the transmission of B. cepacia through the cystic fibrosis patient
      population and looks at possible treatments and current patient management
      approaches.

PMID- 11524999
TI  - General outbreaks of infectious intestinal disease associated with fish and
      shellfish, England and Wales, 1992-1999.
AB  - Between 1992 and 1999 1425 foodborne general outbreaks of Infectious Intestinal
      Disease (IID) were reported to the PHLS Communicable Disease Surveillance Centre.
      Of these, 148 (10%) were associated with the consumption of fish and shellfish.
      Three main aetiologies were identified. Outbreaks associated with fish (47%)
      occurred more frequently in the summer months, and were linked with Scombrotoxic
      fish poisoning caused by the consumption of tuna that was improperly stored.
      Outbreaks associated with molluscs (36%) were associated with the consumption of
      oysters contaminated with viral pathogens, particularly in February. Outbreaks
      associated with the consumption of crustaceans (11%) often involved eating prawns
      that contained either salmonellas or viral pathogens. The maintenance of
      microbial quality from prior to capture/harvesting until the moment of
      consumption, based on a Hazard Analysis and Critical Control Point style
      approach, is essential if gastrointestinal illness associated with such produce
      is to be avoided.

PMID- 11525000
TI  - Epidemiology and diagnosis of meningitis: results of a five-year prospective,
      population-based study.
AB  - Implementation of the advice to give penicillin prior to admission, a fall in the
      lumbar puncture rate and the introduction into routine use of the meningococcal
      polymerase chain reaction (PCR) test are factors that have led us to reassess the
      way meningitis is diagnosed. We examined data for the period 1994-98 from a
      health district of 800,000 population. Of the 355 cases of meningitis reported,
      258 (73%) had either confirmed, probable or possible meningococcal disease. Only
      28% of meningococcal cases had received pre-admission benzylpenicillin. The
      proportion of suspected meningitis cases undergoing lumbar puncture fell over the
      period. It was 79% in 1994 and 61% in 1998 (p < 0.001). After meningococcal PCR
      was introduced in 1996, 73 (68%) meningococcal cases were microbiologically
      confirmed, compared to 72 (48%) before 1996 (p = 0.001). In all cases, age was an
      independent predictor of meningitis mortality, and for meningococcal cases, age
      and serogroup were independent predictors. Advice to general practitioners (GPs)
      to give preadmission benzylpenicillin to any suspected case of meningitis or
      meningococcal septicaemia should be reinforced regardless of age or whether a
      rash is present.

PMID- 11525001
TI  - Prevention of meningococcal infection in laboratory workers--an audit of practice
      in England and Wales.
AB  - A survey of clinical microbiology laboratories in England and Wales found that in
      12% of laboratories a class 1 microbiological safety cabinet was not always used
      for manipulating suspensions of live meningococci. The recommendation that a
      safety cabinet should always be used for such purposes needs reiteration and
      implementation.

PMID- 11525002
TI  - An investigation of the potential risk of an HAV outbreak in a prison population
      following the introduction of cases from a community outbreak.
AB  - Increasing Hepatitis A (HAV) infection has been reported in communities in which
      there is a high level of intravenous drug use. Several cases were identified in a
      local prison and since the risk of transmission within the prison was felt to be
      high, it was decided to determine the prevalence of HAV antibodies in the prison
      population and therefore the number of susceptible inmates. Oral fluid was
      collected from 269 prisoners for testing for antibodies to HAV. Both IgM and IgG
      anti-HAV were assessed so that the percentage susceptible and the number recently
      infected could be ascertained. Eight inmates had evidence of a recent infection.
      Of the remaining 261, only 56 (21%) were immune to HAV. Therefore vaccination
      against HAV in addition to HBV should be considered for intravenous drug users
      and for prisoners remanded from a community where infection is known to be
      occurring.

PMID- 11525003
TI  - Possible undetected outbreaks of cryptosporidiosis in areas of the north west of
      England supplied by an unfiltered surface water source.
AB  - We report a ten-year retrospective analysis of laboratory reports of
      cryptosporidium infection in the North West of England. Weekly report data from
      six health authorities known to have been affected by outbreaks associated with a
      single supply were compared with data from other health authorities in the North
      West. Following graphical representation of report rates, it would appear that
      outbreaks in the six health authorities were considerably more common than the
      average recorded in the national outbreak surveillance system.

PMID- 11525004
TI  - Antibody responses to Hepatitis A vaccine in healthy adults.
AB  - Hepatitis A vaccination has been used in a number of settings to control
      community outbreaks of the disease. Yet United Kingdom guidance for post-exposure
      prophylaxis continues to promote the administration of human normal
      immunoglobulin, despite concerns about the administration of human derived blood
      products. Little is known about the time frame of the antibody response to
      hepatitis A vaccine which, if rapid, could permit the exclusive use of vaccine
      for post-exposure prophylaxis. We report the findings of a pilot study in healthy
      adult volunteers given a single dose of Havrix monodose.

PMID- 11525005
TI  - Capture recapture as a method of determining the completeness of tuberculosis
      notifications.
AB  - Notification of tuberculosis cases is often incomplete but combining data from
      several sources can provide a more accurate estimate of the number of cases. Data
      for the city of Liverpool were collected over an eight-year period from three
      sources: notifications, microbiological records and in-patient discharge coding
      data. Capture-recapture (CR) techniques were used to estimate the total number
      (including unreported cases) of tuberculosis cases in the city. By creating a log
      linear model from the pattern of case replication between data sets, a model of
      best fit was created from which the number of cases present in the population,
      but not identified in any of the data sets, was estimated. False positive
      diagnoses were found in 67/516 (13%) of notifications and in 65/241 (27%) of in
      patient codings. After excluding these, the total combined number of cases from
      all data sources was 473. CR methods identified only twelve extra cases (2.5%)
      making the estimated number of true cases total 485. Of these, in-patient codings
      identified 36.3%, microbiological records 56.3% and notifications 92.6%. It was
      concluded that notification of tuberculosis is very complete in Liverpool.
      Capture-recapture methods can be used to assess completeness of notification data
      in other settings.

PMID- 11525006
TI  - Local review of the provision of prophylaxis and advice to patients without
      functioning spleens.
AB  - General practitioners are routinely reminded to ensure their splenectomised
      patients are offered prophylaxis against infection. We conducted a survey across
      two health authority areas to check how widely this advice was followed. The
      results revealed the need for GPs to review the records of their splenectomised
      patients more systematically.

PMID- 11525007
TI  - Increased risk of cryptosporidiosis from private water supplies.

PMID- 11525008
TI  - Data mining, endogenous retroviruses and human disease.

PMID- 11525009
TI  - Challenges of antibiotic resistance and its surveillance.

PMID- 11525010
TI  - The health and safety of disabled workers.
AB  - The Employment provisions of the Disability Discrimination Act 1995 (DDA) came
      into force on 2 December 1996. The DDA makes discrimination against a disabled
      person, or a person who has had a disability in the past, unlawful. The poor
      employment position of people who have a disability is made worse by the
      widespread belief that disabled people are less productive in employment, that
      they are more likely to leave the organisation because of ill health and that
      they are a risk to other employees on the grounds of health and safety. This
      article looks at the problem of disability and how employers may adjust the
      workplace to accommodate disabled workers, and employ them without compromising
      safety.

PMID- 11525011
TI  - New guidelines on malaria prevention.

PMID- 11525012
TI  - Guidelines for malaria prevention in travellers from the United Kingdom for 2001.
AB  - These guidelines on malaria prevention are designed to aid health care workers
      who advise travellers, particularly those who will be overseas for less than a
      year. The present, and any future, revisions are the responsibility of the
      Advisory Committee on Malaria Prevention in UK travellers (ACMP; membership given
      at the end of the Guidelines). This has replaced the consensus meetings which
      produced earlier versions from 1980 to the the 1997 version. The guidelines are
      in three parts. The first part is a summary that emphasises modifications to the
      advice given in the last set of guidelines, published in 1997. The second part
      discusses the issues addressed in formulating the guidelines. Oversimplified
      lists of recommendations by country can be misleading. The second part also
      addresses the health care worker's consultation with prospective travellers.
      Doctors, practice nurses and pharmacists are asked to read this section to ensure
      that due attention is paid to the traveller's history and destination. The third
      part gives specific recommendations for travellers to specific destinations and
      some details of individual drugs. Fuller information on some drugs now less used
      was given in earlier versions of the guidelines. These guidelines reflect
      experienced professional opinion. Data are inadequate for unequivocal views to be
      given on several issues, but all available evidence has been taken into
      consideration. There is often a range of acceptable options, but to meet the
      requests of general practitioners the guidelines aim to give one recommended
      option and state the alternatives, suggesting when and how different regimens can
      be used to good effect. However, there are now several options for effective
      prophylaxis of highly chloroquine-resistant falciparum malaria, and the choice
      between them will depend on details of the journey and individual preferences.
      Decisions on the terms under which different drugs are licensed for use are the
      responsibility of the Licensing Authority, advised by the Committee on Safety of
      Medicines and not of the ACMP. The guidelines should therefore be read as a
      supplement to and not as a substitute for the relevant data sheets. In concept
      and practice, chemoprophylaxis lies somewhere between vaccinations (for which
      people expect governments to lay down schedules) and treatment of ill people
      (which is determined by individual clinical need and choice). The risks of
      malaria need to be balanced against the risks of the preventive measures, on the
      basis of the data available. Travellers may ask for an explanation of these risks
      and doctors and practice nurses need to be well informed and able to present this
      information to travellers. The second part of these guidelines may also be of use
      to prospective travellers who wish to read about the options themselves. All
      readers are recommended to read part two in its entirety to get a balanced
      picture.

PMID- 11525013
TI  - Environmental echoes.
AB  - Allergy, auto immunity and cancer are becoming more prevalent in the developed
      world. One explanation might be that the immune system required to protect us
      from such problems is being inadequately trained, perhaps due to our increased
      separation from the environment which has shaped our mutating genes since we
      emerged from the primaeval ooze. Those infections which were the essential
      primers of our immunity are being prevented and action is needed to refocus the
      immune response without exposing us to the diseases of the past. In this paper we
      assess our place in relation to the environment and consider ways in which the
      situation can be redressed. There are considerable similarities between the
      immune system and human consciousness. Both enter the world in considerable
      ignorance of the events awaiting them, yet with the genetic ability, endowed by
      millennia of selection and evolution, to experience the world, to interpret and
      act on the experiences and to retain memory of the experiences. In both systems,
      maternal influences and early environmental encounters have profound effects on
      determining the patterns of subsequent responses. Ideally the 'learned' responses
      will benefit or protect the individual but inappropriate responses may lead to
      self damage. As the environment has altered irrevocably, attention must be paid
      to regulating the balance of immunological responsiveness to that expected of the
      normal immunological learning process. This should be possible by novel
      vaccination strategies.

PMID- 11525014
TI  - The serpins: nature's molecular mousetraps.
AB  - A special family of inhibitors, known as the serpins, has evolved an
      extraordinary mechanism to enable the control of the proteolytic pathways
      essential to life. The serpins undergo a profound change in conformation to
      entrap their target protease in an irreversible complex. The solving of the
      structure of this complex now completes a video depiction of the changes
      involved. The serpin, just like a mousetrap, is seen to change with a spring-like
      movement from an initial metastable state to a final hyperstable form. The
      structure shows how this conformational shift not only inhibits the protease but
      also destroys it. A bonus from these structural insights is the realisation that
      a number of diseases, as diverse as thrombosis, cirrhosis and dementia, all share
      a common mechanism arising from similar mutations of different serpins.

PMID- 11525017
TI  - [Stem cell and self-renewal].
AB  - Stem cells are defined as cells with the ability for self-renewal and
      differentiation. Hematopoietic stem cells are well known, and their application
      is useful for the treatment of various kinds of diseases. Recently, neural stem
      cells have been identified even in the adult brain, which has up to now been
      considered to be a tissue with no regenerative capacity. In addition, it has
      emerged that tissue stem cells can differentiate into various kinds of cells
      beyond their original characteristics. Here, we discuss the self-renewal
      mechanisms of embryonic stem (ES) cells, hematopoietic stem cells and neural stem
      cells.

PMID- 11525018
TI  - [Less invasive treatment for lung carcinoma].
AB  - Today, less invasive treatments for lung carcinoma are divided to two categories.
      One is the surgical option which includes 1. surgery by muscle sparing
      thoracotomy, 2. reduced operation represented by segmentectomy or partial
      resection, 3. so-called VATS (video-assisted thoracoscopic surgery), and 4.
      sentinel node navigation surgery. Other options such as photodynamic therapy or
      brachytherapy are also very useful for the treatment of superficial malignancies
      at the hilar zone, because of their lower level of invasiveness.

PMID- 11525019
TI  - [Minimally invasive surgery for breast cancer].
AB  - Breast conservation surgery has become a standard operation as a minimally
      invasive surgery for breast cancer in Japan. Now sentinel lymph node biopsy
      (SLNB), day surgery, and endoscopy assisted surgery are being introduced as more
      minimally invasive surgeries for breast cancer. When blue dye and/or isotope are
      injected into the peri-tumoral breast gland, the sentinel lymph nodes (SLN) can
      be detected easily, and node negative patients can be selected with certainty.
      When no metastasis is found in SLN by frozen section, T1N0 breast cancer patients
      can be treated without lymph node dissection. Using this technique, day surgery
      for patients who have clinically node-negative small breast cancer (less than 1.5
      cm in diameter) is performed under local anesthesia. We have developed an
      endoscopy assisted conservation surgery for breast cancer. Using endoscopy,
      partial or total glandectomy with radical axillary lymph node dissection is
      performed via a 5 cm skin incision on the middle axillary line. When the amount
      of glandectomy is over one third, we perform immediate reconstruction using the
      latissimus dorsi. These minimally invasive surgeries for breast cancer will
      result in a better quality of life for breast cancer patients.

PMID- 11525020
TI  - [Gastric cancer].
AB  - With the development of related instruments and techniques, laparoscopic surgery
      has come to be applied to treatment of gastrointestinal malignancies as a
      minimally invasive surgery. For early gastric cancers with negligible risk of
      lymph node metastasis, endoscopic mucosal resection (EMR), laparoscopic wedge
      resection (LWR), and laparoscopic intragastric mucosal resection (IGMR) have been
      performed. For those with fairly sizable risk of lymph node metastasis,
      laparoscopy-assisted distal gastrectomy (LADG) is applied. Our studies have
      suggest that LADG is more useful than open distal gastrectomy in the management
      of patients with gastric cancer from the viewpoints of curability, minimal
      invasiveness, and quality of life of patients.

PMID- 11525021
TI  - [Minimally invasive treatment of colorectal cancer].
AB  - It may be widely interpreted that minimally invasive treatment of colorectal
      cancer includes endoscopic mucosal resection, transanal endoscopic microsurgery
      (TEM), laparoscopic surgery and open reduction-surgery as well as adjuvant
      treatments such as chemotherapy, radiotherapy and thermotherapy. With the
      development of medical technology and instruments, we have now a wide and new
      range of choices for each cancer stage of patients. However, it is not yet clear
      that minimally invasive treatment necessarily leads to better results in survival
      and recurrent rates of the patients, as compared with conventional surgery. We
      should therefore take into full consideration the lingering problems in selecting
      the new therapies. In this paper, we show the strong and weak points of
      laparoscopic surgery, TEM, right hemi-colectomy preserving Bauhin's valve and
      adjuvant radiotherapy for lower rectal cancer, and discuss ongoing problems.

PMID- 11525022
TI  - [Less invasive medical therapy for hepatocellular carcinoma].
AB  - Since hepatocellular carcinoma (HCC) usually occurs in chronic liver disease,
      especially viral cirrhosis, it often recurs even after surgical resection.
      Because of the high recurrence rate of HCC, less invasive therapies have become
      more common recently, including percutaneous ethanol injection (PEI),
      percutaneous microwave coagulation therapy(PMCT), and radiofrequency
      ablation(RFA). A PEI needle or a coagulation electrode is usually inserted into
      an HCC nodule under ultrasonographic-guidance, and chemical or heat ablation is
      carried out with local or general anesthesia. A patient with a few numbers of
      small HCCs of 3 cm or less in diameter is a good candidate for these therapy
      modalities. Although RFA is the easiest and most effective of these therapies the
      best therapy for each patient is selected according to the number, size, and
      location of target lesions.

PMID- 11525023
TI  - [Minimally invasive treatment of gynecologic cancers].
AB  - This article describes the minimally invasive treatment of cervical, endometrial,
      and ovarian cancers, from the point of view of fertility conservation. It is
      hoped that the treatment fulfills the quality of life needs of female patients.

PMID- 11525024
TI  - [Minimally invasive therapy for bladder and prostate cancer].
AB  - Recently, minimally invasive therapy has been a key word in the medical field.
      Many new therapies have been developed in the field of urology. In this area,
      bacillus Calmette-Guerin (BCG) instillation therapy, transurethral resection of
      the bladder tumor and intra-arterial infusion with irradiation therapy are noted
      as minimally invasive therapies for bladder cancer. Laparoscopic prostatectomy,
      brachytherapy, three-dimensional conformal radiotherapy (3D-CRT) and high
      intensity focused ultrasound (HIFU) have also been developed as minimally
      invasive therapies for prostate cancer. Though the establishment of the validity
      of each treatment will still take time, the best treatment for each patient
      should be chosen case by case, including considerations of postoperative quality
      of life and economic efficiency.

PMID- 11525025
TI  - [Antiangiogenic and antimetastatic effects of toremifene citrate].
AB  - In this study, we demonstrated that toremifene citrate (TOR) inhibited the tube
      formation and migration of human umbilical vein endothelial cells (HUVEC) in
      vitro. Moreover, TOR suppressed angiogenesis in rabbit cornea and lung metastasis
      of human fibrosarcoma HT-1080 cells in nude mice. The antiangiogenic activity in
      vitro was apparent at the concentration of 5 microM which is clinically
      achievable by oral administration of 120 mg/kg of TOR. These results suggest that
      clinical treatment with 120 mg/day of TOR might be expected to exhibit
      antiangiogenesis and antimetastasis effects, in addition to inhibition of
      estrogen-dependent tumor cell growth.

PMID- 11525026
TI  - [Efficacy and toxicity of lenograstim (glycosylated recombinant human granulocyte
      colony stimulating factor) on peripheral blood stem cell harvest in healthy
      donors].
AB  - Peripheral blood stem cell harvest with lenograstim (glycosylated rhG-CSF) was
      performed 12 times from 10 normal donors. Five micrograms/kg of lenograstim was
      administered subcutaneously twice a day (10 micrograms/kg/day) for 4 to 6 days,
      and apheresis was performed on day 5 to 7 depending on the collected CD 34+ cell
      counts. We collected a sufficient number of CD 34+ cells in 9 mobilizations from
      7 donors less than 50 years of age, with a total number of collected CD 34+ cells
      in each mobilization of 22.1 +/- 6.5 x 10(7). In contrast, we could not obtain a
      sufficient number of CD 34+ cells in 2 mobilizations from 3 donors above 50 years
      of age, with a total number of collected CD 34+ cells of 9.8 +/- 3.3 x 10(7).
      Although all donors had adverse events in response to lenograstim administration,
      all of them were grade 2 or less toxicity. These results indicate that peripheral
      blood stem cell mobilization and apheresis by lenograstim is safe and well
      tolerated, but the risk of poor mobilization may become higher in donors more
      than 50 years of age.

PMID- 11525027
TI  - [Evaluation of a combination chemotherapy with nedaplatin and 5-FU for oral
      cancers].
AB  - Nedaplatin (cis-diammine-glycolato platinum: CDGP) is a platinum compound with a
      molecular weight of 303.18 that was recently developed in Japan. There have been
      reports of the antineoplastic effects of Nedaplatin on cancers in the cranio
      cervical region, lung, esophagus, urinary bladder, testis, ovary, and uterus. In
      this study, we performed combined therapy of CDGP and fluorouracil (5-FU) for 8
      patients with oral cancers, and evaluated the results to elucidate the clinical
      effect and adverse side effects. The subjects were 8 patients with squamous cell
      carcinoma (5 males and 3 females aged 33-65 years). The primary carcinoma regions
      were the tongue in 5 patients, oral floor in 2 patients, and mandibular gingiva
      in 1 patient. The T-classification was T2 in 6 patients and T4 in 2 patients, and
      the clinical staging was Stage II in 5 patients, Stage III in 1 patient and Stage
      IV in 2 patients. We first administered 700 mg/m2 5-FU per day from day 1 to day
      5 (total dose 3,500 mg/m2), then 90 mg/m2 CDGP on day 5. The clinical effect was
      evaluated as a partial response in all cases, showing a 100% success rate. The
      histopathological findings of resected tumors were evaluated by Ohboshi and
      Shimozato's classification. One patient was Grade IIA, 5 patients Grade IIB, and
      2 patients Grade III. The adverse side effects were slight myelotoxicity,
      gagging, nausea, alopecia, and stomatitis less than Grade II. Although the oral
      cancers in this study were extroverted superficial ulcerative cancers, and the
      number of patients was low at 8, this combined therapy is considered useful and
      worth evaluating in further accumulated cases.

PMID- 11525028
TI  - [Effect of weekly docetaxel in patients with recurrent breast cancer].
AB  - A pilot trial was conducted to assess the tolerability and efficacy of a regimen
      with weekly docetaxel (TXT) in patients with metastatic breast cancer. The
      chemotherapy regimen consisted of a 30-minute weekly intravenous infusion of
      docetaxel (22-33 mg/m2/wk). Each 8-week cycle included 6 weekly treatments,
      followed by two weeks of rest. Thirteen patients were treated. All patients were
      evaluable for response: 0 CR (0%), 7 PR (53.8%), 3 NC (23.1%), 3 PD (23.1%).
      These results are almost the same as those with the administration of TXT (60
      mg/m2) q3 wks. Toxicities observed were mild (< or = grade 2) and reversible, and
      included fatigue, nausea, neutropenia, and alopecia. This preliminary experience
      suggests a high level of clinical activity and excellent tolerability of the
      chemotherapy regimen at the given dose and schedule in patients with metastatic
      breast cancer.

PMID- 11525029
TI  - [Evaluation of efficacy of ramosetron orally disintegrating tablets and patient
      preference as to the dosage form in gynecological cancer chemotherapy].
AB  - The efficacy of an oral 5-HT3 antagonist, ramosetron orally disintegrating tablet
      (ODT), in the treatment of chemotherapy-induced emesis was investigated in 21
      female patients with cancer. Patient preference for the dosage form was also
      investigated. Eighteen (85.7%) of 21 patients answered that ODT is easy to take.
      Eleven (68.8%) of 16 patients who had previously taken granisetron tablets
      preferred ramosetron ODT to conventional tablets. The complete suppression rate
      of nausea or vomiting was more than 90% for 6 days. No adverse drug reactions
      associated with ramosetron were observed. As ambulatory or home chemotherapy
      becomes frequent, the use of oral 5-HT3 antagonists rather than intravenous
      agents will be increased. Chemotherapy for elderly cancer patients is becoming
      frequently used. Considering these circumstances, it is suggested that ramosetron
      ODT is a palatable and useful treatment of chemotherapy-induced emesis.

PMID- 11525030
TI  - [Postoperative chemotherapy with a novel oral anticancer drug composed of
      tegafur, gimeracil and oteracil potassium to curability C scirrhus type gastric
      cancer].
AB  - We report the a case of 60-year-old male whose final finding was curability C and
      stage IV scirrhus type gastric cancer because of N3, CY1 and DM (+) treated with
      a novel oral anticancer drug composed of tegafur (FT), Gimeracil (CDHP) and
      Oteracil Potassium (Oxo) in a molar ratio of 1:04:1 after operation. This drug
      was administered orally twice daily after meals at a dose of 80 mg/body/day. One
      cycle consisted of consecutive administration for 28 days and 14 days rest, and
      this treatment cycle was repeated twice. Postoperative abdominal CT showed
      swollen paraaortic lymph nodes regarded as metastasis. However, they were reduced
      after 1 cycle and remained so. The serum carcinoembryonic antigen (CEA) level had
      decreased after 1 cycle. The patient's performance status (PS) had also recovered
      without severe side effects. It was considered that this anticancer drug composed
      of FT, CDHP and Oxo was effective to scirrhus type gastric cancer and useful as
      an adjuvant chemotherapy in view of the patient's living quality.

PMID- 11525031
TI  - [A case of hepatic metastasis of gastric cancer responding to TS-1, administered
      for two consecutive weeks and one week rest].
AB  - We have treated a case of hepatic metastasis of gastric cancer that has responded
      well to TS-1. The patient was a 68-year-old male, who underwent distal
      gastrectomy for gastric cancer. After surgery 5'-deoxy-5-fluorouridine (5'-DFUR)
      800 mg/day was administered orally for two months. Grade 4 diarrhea appeared, so
      administration of 5'-DFUR was discontinued. Afterward the patient was followed
      with no chemotherapy. Liver metastasis (S6, 3 cm in diameter) was found at twelve
      months after surgery. 5'-DFUR (800 mg/day) was administered orally everyday.
      Grade 3 diarrhea appeared and metastasis showed NC after four weeks. 5'-DFUR
      administration was discontinued. Seventeen days later TS-1 (80 mg/day) was
      administered orally everyday for 2 weeks, followed by 1 week rest, as one course.
      Two courses of TS-1 administration resulted in a marked reduction of the liver
      metastasis, for a PR (75% reduction). After 3 courses, the liver metastasis
      showed CR. The patient is alive without recurrence after 12 courses. This TS-1
      administration regimen was effective and tolerable for a patient with liver
      metastasis from gastric cancer.

PMID- 11525032
TI  - [A case of nonresectable scirrhous type gastric cancer treated by hypertensive
      subselective chemotherapy with pharmacokinetic modulating chemotherapy].
AB  - There have been few effective chemotherapeutic regimens for scirrhous type
      gastric cancer. A 62-year-old male patient was admitted to our hospital because
      of anorexia and abdominal discomfort. Gastroendoscopy showed a type 4 advanced
      gastric cancer in the upper gastric body. Histologic study of biopsy specimens
      from the tumor revealed poorly differentiated adenocarcinoma. Examination by
      computed tomography and ultrasonography revealed swollen paraaortic lymph nodes
      and peritonitis carcinomatosa. The patient was diagnosed as having a
      nonresectable scirrhous type gastric cancer with peritonitis carcinomatosa and
      paraaortic lymph node metastasis. This patient was treated weekly with an
      intraarterial 5-FU (500 mg) and MTX (100 mg) including AT-II by a subcutaneously
      implanted port system placed into the thoracic aorta. Furthermore, he was
      administered tegafur/uracil (400 mg/day) 5 days weekly as a pharmacokinetic
      modulating chemotherapy (PMC). After eight courses of treatment of PMC,
      paraaortic lymph node swelling and ascites decreased. This chemotherapy produced
      a partial response in the peritonitis carcinomatosa and paraaortic lymph nodes.
      This chemotherapy was repeated preoperatively. We reconsidered this case to show
      indications for operation. The patient died suddenly of acute heart failure
      before the operation. This therapy was considered an effective treatment for
      nonresectable gastric cancer.

PMID- 11525033
TI  - [Significance of laparoscopy for response assessment of chemotherapy in gastric
      cancer].
AB  - We performed laparoscopy before and after chemotherapy in two patients with
      relapsed and advanced gastric cancer, whose major metastatic sites had been
      diagnosed as being in the peritoneum. A change in tumor responses when assessed
      by laparoscopy was found. Case 1: A 63-year-old man presented with an umbilical
      metastasis and suspected peritoneal metastases after gastrectomy. Laparoscopy
      revealed peritoneal metastases before chemotherapy. After one course of
      chemotherapy the umbilical tumor disappeared (CR). Laparoscopy after two courses
      of chemotherapy revealed increasing peritoneal metastases (PD). The overall
      response was PD. Case 2: A 67-year-old woman was referred to our hospital with a
      diagnosis of type 4 gastric cancer. Staging laparoscopy revealed massive lymph
      node metastases and the patient was positive in peritoneal washing cytology.
      After four courses of chemotherapy, the primary tumor and the metastatic lymph
      nodes had decreased in size (PR). In contrast, laparoscopy revealed increasing
      peritoneal metastases (PD). The overall response was PD. CONCLUSION: In patients
      with peritoneal and other modes of metastasis, tumor response to chemotherapy may
      be misjudged by conventional imaging alone. Intraperitoneal examination by
      laparoscopy provides accurate information, including the tumor response to
      chemotherapy.

PMID- 11525034
TI  - [Chemoradiotherapy and salvage surgery in a patient with advanced esophageal
      cancer].
AB  - We report a case of advanced esophageal cancer, which was treated by
      chemoradiotherapy combined with surgical treatment. Moreover, 14 advanced
      esophageal cancer patients treated by chemoradiotherapy are discussed. The
      chemoradiotherapy showed beneficial control of the tumor; however, it sometimes
      leads to esophageal stenosis and ulcer. We conclude that additional salvage
      surgery is needed for such complications.

PMID- 11525035
TI  - [Tissue platinum distribution and the effect following intra-arterial injection
      of cisplatin to metastatic liver cancer--a case report].
AB  - A 63-year-old male with advanced esophageal cancer was admitted to our hospital.
      He received neoadjuvant chemotherapy with intravenous cisplatin and fluorouracil
      (5-FU), and underwent resection of the esophagus and placement of a gastric tube.
      Two months later, multiple metastases appeared in the right lobe of the liver.
      Intermittent arterial infusion chemotherapy with cisplatin and 5-FU were
      performed. To selectively infuse the drugs into the right hepatic artery, the
      left hepatic artery was embolized. Treatment had a marked effect in the right
      lobe, but new lesions were subsequently discovered in the left lobe. The patient
      died of pleuritis 27 days after the end of cisplatin infusion and 12 months after
      surgery. In total, 465 mg of cisplatin and 20 mg of nedaplatin were administered.
      At autopsy, tissue samples were collected to measure the platinum concentration.
      The result showed the highest value to be in the right lobe, 4.8 times as high as
      that in the left lobe. It is suggested that the concentration of platinum in
      tissue is correlated with the anticancer effect of cisplatin to the tissue,
      despite of the traditional view that the tissue concentration and the effect are
      not related.

PMID- 11525036
TI  - [A case of pseudomyxoma peritonei treated successfully with intraperitoneal
      administration of CBDCA and etoposide, followed by local delivery of dextran with
      CDDP during surgery].
AB  - A 77-year-old woman was diagnosed as having pseudomyxoma peritonei originating in
      the ovary or appendix. Low-molecular dextran and CDDP 70 mg was administered
      directly into the peritoneal cavity, followed by initial exploratory laparotomy
      with total abdominal hysterectomy, bilateral salpingo-oophorectomy, appendectomy,
      and omentectomy. During surgery, an implantable port system was positioned to
      facilitate repeated intraperitoneal administration. Dextran was used with
      mucolytic therapy and augmentable efficacy of drug administered simultaneously.
      Within three weeks after surgery, four courses of intraperitoneal CBDCA 300 mg
      and etoposide 100 mg were administered at four-week intervals. The patient has
      remained in good general condition with no sign of recurrence for one year. This
      chemotherapy regimen has minimum side effects and seems effective in maintaining
      quality of life.

PMID- 11525037
TI  - [The role of tumor markers in the treatment of germ cell tumor].
AB  - Alfa fetoprotein (AFP), human chorionic gonadotropin (HCG), beta HCG and lactate
      dehydrogenase (LDH) are powerful markers of germ cell tumors. The role of tumor
      markers is very important in the diagnosis, treatment and follow-up of germ cell
      tumors, respectively. We can often deduce the histological typing of germ cell
      tumors by tumor marker elevation before surgery. Tumor markers also frequently
      provide clues as to outcome in individual cases before treatment. The half-life
      of tumor markers during chemotherapy indicate the effect of the treatment. The
      optimal regimen of chemotherapy should therefore be selected based on the half
      life of tumor markers. Normalized tumor markers designate the phase of discussion
      on surgical indications. Determination of tumor markers is important in following
      patients after treatment of germ cell tumors. The elevation of serum tumor
      markers denotes recurrence and is often the first sign of treatment failure.

PMID- 11525038
TI  - [Declared diseases, observed diseases and health priorities in a Benin rural
      district].
AB  - A project of a humanitarian action was preceded by a health diagnosis of a
      population in the rural district Bonou in Benin. A diagnosis of perception was
      set up by the interviews among the population and the local health professionals.
      That diagnosis was completed by an objectified diagnosis originating from the
      analysis of 460 consultations performed in Benin end 1998- beginning 1999. The
      cross-sorting between the diagnosis of perception and the objectified diagnosis
      pointed out four public health problems: malaria, bronchial asthma, infectious
      diarrhoeas and Buruli ulcer with respective prevalences of 9%, 6%, 3% and 0.9%.
      The prevalence of bronchial asthma fluctuates from 4% in dry areas to 8% in wet
      areas (Chi 2 = 3.50; p = 0.06). The role of house dust mites is suspected because
      of those ecological arguments to which is added clinical reasoning. Bronchial
      asthma was chosen as a priority health problem because of the feasibility and
      acceptance of a survey which aims at pointing out the allergic etiology. The
      confirmation of that etiology will enable in that case the decrease of the
      allergenic pressure, particularly well adapted solution in the Southern
      countries. Therefore a humanitarian action is foreseen to apprehend the
      etiologies of bronchial asthma in the rural district Bonou in Benin in 2000.

PMID- 11525039
TI  - [Fiscal revenues derived from tobacco sales to young people in France].
AB  - This article examines the public revenues for France from tobacco sales to youths
      in 1997. The result is compared to the means of prevention the same year. Public
      revenues are estimated from: the number of adolescents divided into age groups
      (range: 12 to 19), the smoking rates by age group, the number of cigarettes
      smoked daily in each age group, the price of a cigarettes pack and the percentage
      of taxes. In 1997, almost 1.7 million youths were smokers and they smoked 240
      million of cigarette boxes annually. This sale represented 4.7 billion of French
      Francs (FF): 3.615 billion of taxes, 380 million for tobacconists' and 762
      million for the tobacco industry. The same year prevention represented less than
      FF 0.5 per year and inhabitant, one of the lowest ratios in developed countries.

PMID- 11525040
TI  - [Scientific non-engagement for respect of a person's fundamental rights].

PMID- 11525041
TI  - [Ten years experience in Mali community health centers].
AB  - At the end of 10 years' existence, the community health centres of Mali show a
      way of organisation which meets the public health requirements and demands of
      financial viability of any health establishment. Their originality lays in
      several factors: their legal personality, their private status, their financial
      support of the medical staff, their management by a users association and the
      public utilities agreement they have signed with the department. In spite of
      their success which makes their numbers reach 350, they suffer from great
      deficiencies, which are resulted by the lack of democratic traditions within the
      associations, a inappropriate transparency of their accounts and an inefficient
      supervision from the part of the department. The main questions posed by this new
      experience concern the limits of the concept of community, the importance of
      citizenship in the development dynamics, the participation of private
      institutions in the accomplishment of public utilities, the jacobin and
      authoritarian attitude of the department representatives, the contradictions
      between multiplication of centres to improve geographic access and the
      requirements of financial viability.

PMID- 11525042
TI  - [Analysis methods for educational needs assessment for family caregivers of HIV
      positive or AIDS patients in Thailand].
AB  - Identification of educational needs of natural helpers for the home-based care of
      persons living with HIV or AIDS. Surin, Thailand. The very significant increase
      in the number of persons living with aids in Thailand, (1995: 20,154 notified
      cases; 1996: 23,309 cases; 1997: 25,064 cases), and the insufficiency of medical
      care for patients within Thailand's health structures, have driven Medecins Sans
      Frontieres (MSF) to put in place since 1996 a home-based care project in Surin
      province (North-Eastern Thailand). In Thai culture, the sick are commonly cared
      for by one family member, known as the natural helper. An evaluation of the
      health situation showed that natural helpers who took care of a family member
      living with HIV or aids were not prepared for this situation. In order to better
      define the tasks that they ought to perform, we carried out a needs assessment in
      three interdependent steps: a records analysis of the activities delegated to
      natural helpers by nurses; an enquiry on the acceptability of natural helpers to
      carry out these cares and on the perceived usefulness of being trained; an expert
      consensus on the cares to be carried out by the natural helpers, obtained by the
      Delphi method. Twenty seven cares were identified as being able to be provided by
      natural helpers. They constitute as a list of reference for the training for
      natural helpers. This work has shown a social coherence between the different
      actors of the project. At no stage was the role of the natural helpers
      questioned. On the contrary, natural helpers have a privileged place within the
      family and in the home-based care programme. Natural helpers will allow
      continuity of care between the health structures and the patient's home.

PMID- 11525043
TI  - [Information and documentation in public health].

PMID- 11525044
TI  - [Prevalence of obesity in children: study in the primary public Parisian
      schools].
AB  - Obesity is an important risk factor in public health. In Paris, few statistical
      data are available in this area. The purpose of the present study is to evaluate
      the prevalence of overweight and obesity in 10 years-old children attending Paris
      elementary schools (cours moyen deuxieme annee--CM2--last level of the elementary
      school). 148 classes were randomly selected, gathering 3,621 schoolchildren 10
      years 6 months old. 66 doctors in charge of health at school participated in the
      study, doing the measurements of weight, size and collecting also the weight and
      size at birth and at the "grande section-GS-level" (last level of the infant
      school, 5 years-old children) from the individual health file of the
      schoolchildren. The statistical analysis was based on the study of distributions
      of the observed Quetelet index (Q0) at the different ages, compared to French
      reference curves. A logistic regression analysis was performed to determine
      whether birth weight and GS weight predict obesity in CM2. In GS and in CM2,
      observed Quetelet indices are over expected values: in CM2, 22.8% of boys and
      25.6% of girls exceed the reference value Q90; the prevalence of obesity (Q0 > or
      = Q97) is 13.4% in boys and 13.5% in girls. Among the variables "term", "weight
      at birth", weight in GS level and "gender", the weight in GS level is the only
      predictive factor of obesity in CM2 level. The situation in Paris appears to be
      serious. Preventive actions are needed at early stages to try to stop and, if
      possible, to reverse the present increase of overweight. In this context, school
      doctors have to play a prominent role.

PMID- 11525045
TI  - [Hygiene is not cleanliness. For a new definition of hygiene promotion in
      emergency humanitarian aid].
AB  - Following the Kosovo crisis, this paper questions the contents of hygiene kits to
      be distributed to refugees, the definition of hygiene and the hygiene promotion
      practises in emergency aid work. Hygiene promotion cannot be reduced to cleanness
      promotion. We have to consider refugees' psychosocial needs and trauma as well as
      the problems of refugees settlement as a community and of community mobilisation
      to conceive programmes meeting population's needs and demands. Hygiene promotion
      should include systematic attempts to implement community services by volunteer
      refugees. One has to be careful also that the financial mechanisms of aid do not
      pervert programmation.

PMID- 11525046
TI  - [Biomedical research: private interests and public interests].

PMID- 11525047
TI  - Fluid and electrolyte abnormalities.
AB  - Patients with cancer are at risk for developing a variety of fluid and
      electrolyte disturbances caused by the disease process or by complications from
      therapy. An understanding of the pathophysiology of these potential abnormalities
      allows the clinician to manage patients expectantly and to avoid severe metabolic
      disarray by correcting imbalances promptly.

PMID- 11525049
TI  - Malignancy and renal disease.
AB  - A variety of renal diseases and electrolyte disorders may be associated with
      various malignancies or with treatment of malignancy with chemotherapeutic drugs
      or radiation. This article reviews renal disease in cancer patients, which
      constitutes a major source of morbidity and mortality.

PMID- 11525048
TI  - Infectious morbidity in critically ill patients with cancer.
AB  - Infection frequently complicates the course of cancer treatment and often
      adversely affects the outcome. Patients have a greater tendency for acquiring
      infections caused by opportunistic microorganisms. Agents with low virulence
      potential may lead to invasive and often life-threatening infections because of
      altered host immune function. The immune dysfunction may be caused by the
      underlying malignancy, by antineoplastic chemotherapy, or by invasive procedures
      during supportive care.

PMID- 11525050
TI  - Bleeding and thrombotic complications in critically ill patients with cancer.
AB  - Alterations in hemostasis are common in patients with cancer admitted to the ICU.
      Depending on the underlying disease and specific hemostatic abnormality, the
      patient with cancer may develop bleeding, thrombosis, or both, such as DIC.
      Bleeding complications usually result from abnormalities in platelets or
      deficiency of coagulation factors and require specific blood or coagulation
      factor replacement. Similarly, critically ill patients with cancer are
      predisposed to thrombotic complications such as DVT, PE, and central vein
      thrombosis, the last as a result of the widespread use of long-term indwelling
      catheter devices. Advances in diagnostic imaging and the availability of newer
      and more potent anticoagulant agents have facilitated the care of these patients
      greatly. Ultimately, it is hoped that a thorough understanding of the various
      disturbances in hemostasis, innovative treatment approaches, and implementation
      of preventive strategies in patients with cancer will lead to decreased morbidity
      and improved survival rates of critically ill patients with cancer in the ICU.

PMID- 11525051
TI  - Acute respiratory failure in critically ill patients with cancer. Diagnosis and
      management.
AB  - Respiratory failure remains a common cause of admission to the ICU for patients
      with cancer, regardless of the nature of malignancy. The diagnosis and management
      of ARF in patients with cancer poses special challenges to the intensivist.
      Depending on the type of cancer, the degree of immunosuppression, underlying
      comorbidities, the modality of cancer treatment, progression or spread of
      underlying cancer, and disease- or therapy-associated complications are the most
      common causes of ARF in these patients. Despite significant advances in
      antineoplastic therapies and supportive management in the ICU, the mortality rate
      of patients with cancer with ARF remains high. Severity-of-illness scoring
      systems and mortality probability models, although useful in discriminating
      between survivors and nonsurvivors in large groups of critically ill patients,
      should not be used alone to justify reluctance in admitting individual patients
      with cancer with potentially reversible respiratory failure to the ICU. Close
      collaboration between oncologists and intensivists will ensure the establishment
      of clear goals and direction of treatment for every patient with cancer who
      requires mechanical ventilation.

PMID- 11525052
TI  - Evaluation of pulmonary infiltrates in critically ill patients with cancer and
      marrow transplant.
AB  - Pulmonary infiltrates in critically ill patients with cancer or marrow transplant
      can be evaluated by the differential diagnosis presented at the beginning of this
      article. The patient's quantitative immune system dysfunction, epidemiologic
      history and chest radiographic findings (pattern, rapidity, and time of onset)
      will help focus the differential diagnosis. In this patient population, however,
      common diagnoses can have atypical presentations, unusual diagnoses do occur, and
      more than one process may be responsible for a patient's infiltrates. Early
      bronchoscopy to rule out infection is the focus of diagnostic testing. Surgical
      lung biopsy in this patient population has a low yield.

PMID- 11525053
TI  - Critical care of the hematopoietic stem cell patient.
AB  - Hematopoietic stem cell transplantation is evolving into a treatment modality
      with expanding indications and volume and with excellent outcomes, although it
      carries significant risk for morbidity and mortality affecting most major organ
      systems and often requires ICU care. With continuing improvements in supportive
      care and specific therapy of complications following HCT including the open-lung
      strategy of mechanical ventilation, use of nitric oxide, less toxic myeloablative
      regimens, newer classes of antibiotics, and improved immunosuppression
      strategies, it is hoped that mortality in this setting will continue to decline
      in coming years.

PMID- 11525054
TI  - Circulatory shock.
AB  - Patients with malignancy may present with acute circulatory compromise requiring
      ICU monitoring and care. The clinician must be familiar with a multiplicity of
      acute and chronic medical conditions common to the general population and also
      with conditions directly related to cancer or therapy thereof.

PMID- 11525055
TI  - Critical care of patients with cancer. Surgical considerations.
AB  - Surgical evaluation of and therapy for the critically ill cancer patient continue
      to present significant challenges despite, or perhaps in part because of, an
      ongoing technologic refinement of therapeutic modalities within a modern ICU.

PMID- 11525056
TI  - Nutritional support in critically ill patients with cancer.
AB  - Nutritional depletion is a common problem seen in critically ill patients with
      cancer and is associated with increased morbidity and mortality. Infection and
      injury activate a cascade of metabolic events that leads to a poor nutritional
      state and wasteful energy consumption. The goals of nutritional support entail
      minimizing starvation, preventing nutrient deficiencies, supporting or improving
      immune function, and facilitating tissue repair and wound healing. Further
      understanding of the metabolic changes of illness will improve effective
      regulation of the inflammatory events occurring in critically ill patients.
      Multiple clinical parameters are available to assess the nutritional status in
      critically ill patients, but no standard recommendations can be made at this
      time. The use of these parameters can be appropriate, provided that their
      limitations are understood clearly. The development and standardization of
      objective parameters to identify patients at risk or with subclinical
      malnutrition are needed. Enteral and parenteral feedings are safe and effective
      methods to deliver nutrients to critically ill patients with cancer who are
      unable to ingest adequate amounts orally. Early nutritional support should be
      instituted in the appropriate clinical setting. Specialized nutritional solutions
      and supplements require careful consideration in patients with renal, hepatic,
      cardiac, or pulmonary disorders. The unselective use of nutritional support is
      not indicated in well-nourished patients with cancer undergoing surgery,
      chemotherapy, or radiotherapy in whom adequate oral intake is anticipated.
      Nutritional support remains an important adjunctive therapy in the overall
      management of critically ill patients. Continued clinical investigations in
      nutrition are necessary to identify other groups of patients who can benefit from
      nutritional interventions.

PMID- 11525057
TI  - Special nursing considerations.
AB  - Caring for a critically ill patient with cancer requires another dimension of
      care when compared with caring for patients in a general ICU. The oncology
      critical care staff deals with an acute event and with the multidimensional
      aspects of care of a patient with a cancer diagnosis. Goals of care include a
      reduction in the number and severity of disease- and treatment-related adverse
      sequelae. Effective management requires a multidisciplinary approach to care.
      Skilled and knowledgeable care and communication among all members of the team
      are essential to prevent, minimize, and treat these symptoms and to achieve
      optimal patient outcomes.

PMID- 11525058
TI  - Intensive care, mechanical ventilation, dialysis, and cardiopulmonary
      resuscitation. Implications for the patient with cancer.
AB  - The broad range in mortality rates seen in the critically ill cancer population
      reflects the fact that cancer is a heterogeneous disease, affecting a
      heterogeneous population at different stages of care. Patients, families, and
      physicians frequently agonize about the utility of CPR and ICU care and whether
      this care should be offered. Understanding the goals of care, respecting
      autonomy, and knowing the likelihood of benefits and burdens of these
      interventions are critical in making these difficult decisions.

PMID- 11525059
TI  - End-of-life decisions in cancer care.
AB  - End-of-life decisions in critically ill patients with cancer are often complex
      and fraught with emotion. End-of-life care involves a multidisciplinary approach
      that takes into account the patient and family's desires and the goals of
      therapy. Decisions regarding the use of life-support technology at the end of
      life encompass an outcomes and goal-oriented approach. Ethical, medical, legal,
      and economic issues should be considered in the assessment of life-support
      technologies and directives for their appropriate use in the ICU.

PMID- 11525060
TI  - Skewed distribution of morphological character scores and molecular markers in
      three interspecific crosses in Rosa section Caninae.
AB  - The dogroses, Rosa section Caninae, are all polyploid and characterised by their
      unbalanced meiosis; the pollen parent contributes one genome, whereas the seed
      parent contributes 3-5 genomes depending upon ploidy level of the species. As a
      result, genetically determined traits are expected to be matroclinally inherited.
      In the present study, the transmittal of genetic material was studied using
      manually scored reproductive characters (ovary and sepals), automated image
      analysis of leaflet shape (Fourier coefficients), and molecular markers (RAPD).
      The plant material consisted of a pair of reciprocal crosses between R. sherardii
      and R. villosa, a R. rubiginosa x R. sherardii cross and offspring obtained from
      selfing or within-population crosses of the parental species. All but one of the
      maternal markers were transmitted to all the offspring plants, whereas only 41%
      of the paternal markers were transmitted to all of them, 23% were never
      transmitted and 36% reached only one or two of the offspring plants. Canonical
      variates analyses (CVA) based on the vegetative characters could easily separate
      the offspring groups representing parental species and also all three
      hybridogenous offspring groups from each other, whereas CVA based on reproductive
      characters failed to separate R. sherardii x R. villosa from its seed parent, but
      otherwise distinguished all offspring groups. The study shows that the expression
      of characters as well as molecular marker inheritance is dependent upon the
      direction of the cross, and on the species involved. It also demonstrates the
      importance of employing several different types of character sets for an improved
      comprehension of the effects of the peculiar canina meiosis.

PMID- 11525061
TI  - Formation and morphology of dark puffs in Drosophila melanogaster polytene
      chromosomes.
AB  - The formation of unusual dark puffs in Drosophila melanogaster polytene
      chromosomes has been studied by electron microscopic (EM) analysis. Fly stocks
      transformed by the P[ry; Prat:bw] and P[hs-BRC-z1] constructs were used. In the
      former the bw gene is under the promoter of a housekeeping gene, Prat; in the
      latter the Br-C locus, mapping to the dark puff 2B, is under the promoter of a
      heat-shock gene, hsp70. Inserted into region 65A of the 3L chromosome, the
      Prat:bw copies give rise to structures which are morphologically reminiscent of
      the so-called "dark" puffs. In contrast, insertion of P[hs-BRC-z1] into region
      99B of the 3R chromosome causes a regular "light" puff of form. Comparative
      analysis of the dark puffs--both transgenic and natural--suggests that there
      might be at least two mechanisms underlying their formation. One is a local
      incomplete decondensation of activated bands, characteristic of the so-called
      small puffs. The other is the formation of ectopic-looking contacts between the
      bands adjacent to the puffing zone. Transposition of the DNA, from which such a
      puff develops, causes a regular light puff to form at the new location.
      Heterochromatic regions do not appear to be directly involved in puffing.

PMID- 11525062
TI  - Mouse chromosome 19 and distal rat chromosome 1: a chromosome segment conserved
      in evolution.
AB  - Through a combination of radiation hybrid mapping and studies by FISH and zoo
      FISH we have made a comparative investigation of the distal portion of rat
      chromosome 1 (RNO1) and the entire mouse chromosome 19 (MMU19). It was found that
      homologous segments of RNO1 and MMU19 are similar in banding morphology and in
      length as determined by several different methods, and that the gene order of the
      46 genes studied appears to be conserved across the homologous segments in the
      two species. High-resolution zoo-FISH techniques showed that MMU19 probes
      highlight only a continuous segment on RNO1 (1q43-qter), with no detectable
      signals on other rat chromosomes. We conclude that these data suggest the
      evolutionary conservation of a chromosomal segment from a common rodent ancestor.
      This segment now constitutes the entire MMU19 and a large segment distally on
      RNO1q in the mouse and rat, respectively.

PMID- 11525063
TI  - Isolation of cDNA clones differentially expressed in flowers of apomictic and
      sexual Paspalum notatum.
AB  - Paspalum notatum is a subtropical forage grass, which reproduces by either
      sexuality or aposporous gametophytic apomixis. The objective of this work was to
      identify and isolate mRNA transcripts differentially expressed during the
      development of the megagametophyte from spikelets of apomictic and sexual P.
      notatum. Crossing of a sexual mother plant with an apomictic pollen donor
      generated a progeny family segregating for reproductive mode. Individuals from
      this F1 family were cytoembryologically classified as sexual or apomictic.
      Spikelet mRNA compositions from both groups of plants were compared by
      differential display using an RNA-bulked procedure. Fifty primer combinations
      were assayed to generate nearly 2,500 total bands in the fingerprints. Three
      transcripts expressed at higher levels in apomictic plants (apo417, apo398, and
      apo396) were identified, isolated and cloned. Sequencing showed a high level of
      homology among the isolated clones. Analysis by RT-PCR Southern blots followed by
      densitometric studies confirmed that expression reached a level around 30 times
      higher in apomictic than in sexual individuals and was probably induced at early
      stages of the megagametophyte development. Genomic DNA from the parental and the
      F1 progeny plants showed 4-5 bands when hybridised with apo417 in Southern blots.
      Comparisons to the sequence data banks revealed no identities to genes of known
      function. However, a putative deduced 3' protein fragment showed homology to the
      well-characterised KSP multi-phosphorylation domain previously detected in
      several cdc2-regulated cytoskeletal proteins.

PMID- 11525064
TI  - Genetic diversity of allozymes in turnip (Brassica rapa L. var. rapa) from the
      Nordic area.
AB  - Genetic diversity and relationships based on isozymes were studied in 31
      accessions of turnip (Brassica rapa L. var. rapa). The material included
      varieties, elite stocks, landraces and older turnip of slash-and-burn type from
      the Nordic area. A total of 9 isozyme loci and 26 alleles were studied. The
      isozyme systems were ACO, DIA, GPI, GOT, PGM, PGD and SKD. The level of
      heterozygosity was reduced in the landraces, but it was high for the variety
      group 'Ostersundom'. Turnip has a higher genetic variation than other crops
      within B. rapa and than in other species with the same breeding system. The
      genetic diversity showed that 18.7% of the genetic variation was within the
      accessions, and the total H tau value was 0.358. Gpi-I and Pgd-I showed the
      lowest variation compared with the other loci. The cluster analysis revealed five
      clusters, with one main cluster including 25 of the 31 accessions. The dendrogram
      indicated that the variety group 'Ostersundom' clustered together whereas the
      variety group 'Bortfelder' was associated with country of origin. The landraces
      were spread in different clusters. The 'slash-and-burn' type of turnip belonged
      to two groups.

PMID- 11525065
TI  - Expression of resistance to Blumeria graminis f.sp. tritici in 'Chinese Spring'
      wheat addition lines containing chromosomes from Hordeum vulgare and H. chilense.
AB  - Blumeria graminis f.sp. tritici (syn. Erysiphe graminis f.sp. tritici) causes an
      important disease of wheat (powdery mildew) to which Hordeum vulgare and H.
      chilense are resistant. The study of chromosomal addition lines of H. vulgare and
      H. chilense in wheat showed that they possessed resistance to wheat powdery
      mildew. This was expressed as a reduction of disease severity but it was not
      associated with increased macroscopically visible necrosis. The resistance is of
      broad genetic basis, conferred by gene(s) present on different chromosomes of
      both H. vulgare and H. chilense. The feasibility of transferring this resistance
      to wheat is discussed.

PMID- 11525066
TI  - Development and mapping of Oryza glumaepatula-derived microsatellite markers in
      the interspecific cross Oryza glumaepatula x O. sativa.
AB  - Wild germplasm of domesticated crops is a source of genetic variation little
      utilized in breeding programs. Interspecific crosses can potentially uncover
      novel gene combinations that can be important for quantitative trait analysis.
      The combined use of wide crosses and genetic maps of chromosomal regions
      associated with quantitative traits can be used to broaden the genetic basis of
      rice breeding programs. Oryza glumaepatula is a diploid (AA genome) wild rice
      species native from South and Central America. A genetic map was constructed with
      162 PCR-based markers (155 microsatellite and 7 STS markers) using a backcross
      population derived from the cross O. glumaepatula, accession RS-16 from the
      Brazilian Amazon Region x O. sativa BG-90-2, an elite rice inbred line. The map
      included 47 new SSR markers developed from an O. glumaepatula genomic library
      enriched for AG/TC sequences. All SSR markers were able to amplify the O. sativa
      genome, indicating a high degree of SSR flanking region conservation between O.
      glumaepatula and O. sativa species. The map covered 1500.4 cM, with an average of
      one marker every 10 cM. Despite some chromosomes being more densely mapped, the
      overall coverage was similar to other maps developed for rice. The advantage to
      construct a SSR-based map is to permit the combination of the speed of the PCR
      reaction, and the codominant nature of the SSR marker, facilitating the QTL
      analysis and marker assisted selection for rice breeding programs.

PMID- 11525067
TI  - A new repetitive DNA sequence family in the olive (Olea europaea L.).
AB  - Two families of repeated DNA sequences were cloned from Olea europaea ssp sativa
      cv. "Picual". The first repetitive DNA is organized in a tandem repeat of
      monomers of 178 bp. Sequencing of several clones showed that it is relatively A-T
      rich (54.49%) and possesses short direct and inverted subrepeats as well as some
      palindromic sequences. Comparison between the monomers revealed heterogeneity of
      the sequence primary structure. This repetitive DNA is present in several
      cultivars of olive cultivates. Comparison of sequences with other repetitive DNAs
      described in Olea europaea has been carried out. No significant similarity was
      found. All the obtained results suggest that this repetitive DNA described here
      is a new family of repetitive DNA. The second repetitive DNA is organized in a
      tandem repeat of monomers of 78 bp. This second family of repetitive DNA showed
      significant similarity with other repetitive DNAs previously described in Olea
      europaea. Their existence in new cultivars of olive is shown.

PMID- 11525068
TI  - Genome composition, stability and fertility of hexaploid alloploids between
      Triticum turgidum var. carthlicum and Leymus racemosus.
AB  - Hexaploid alloploids between the tetraploid wheat Triticum carthlicum and the
      perennial tetraploid Leymus racemosus were analysed for chromosome composition
      and cytogenetic stability. GISH analysis showed different lines to have from 11
      to 16 Leymus chromosomes. The alloploids showed a relatively high frequency of
      univalents in meiotic metaphase and of aneuploid plants and hence they are not
      stable. The seedset is lower than in wheat, but high enough to secure a safe
      propagation and preservation. The alloploids are discussed in relation to
      widening the genetic variation of breadwheat and wheat breeding.

PMID- 11525069
TI  - Inbreeding depression for size but not for symmetry in Drosophila melanogaster.

PMID- 11525070
TI  - Special barley beta-amylase allele in a Finnish landrace line HA52 with high
      grain enzyme activity.

PMID- 11525071
TI  - T wave positivity in resting electrocardiogram predicts preserved systolic
      thickening in chronic anterior Q wave myocardial infarction: an echocardiographic
      study.
AB  - AIM: After ST elevation myocardial infarction, ST segment and T wave changes
      generally resolve, but in some patients T waves keep their negative components
      for a long time. The aim of this study is to evaluate the pathophysiological
      implications of persistent negative T waves and restored positive T waves in the
      chronic stage of Q wave myocardial infarction. METHODS: We studied 30 patients
      with a previous anterior wall ST elevation myocardial infarction (more than one
      year follow-up) and presenting Q waves in at least three consecutive precordial
      leads in the standard 12-lead electrocardiogram at rest. Patients were divided
      into two groups according to the T wave pattern in leads with Q waves: positive T
      group consisting of patients in whom all T wave components showed an upright
      configuration; and a negative T group consisting of patients in whom T waves were
      are least partly inverted. We used echocardiography to measure systolic
      thickening of the interventricular septum within the infarction area. Systolic
      thickening was considered significant when end-systolic thickness was greater
      than end-diastolic thickness by > 25% in proportion and > 1 mm in absolute value.
      RESULTS: Significant systolic thickening was demonstrated in 14 (74%) of the 19
      positive T patients and in one (9%) of the 11 negative T patients (odds ratio
      8.1; 95% CI, 1.2 to 53.5; p = 0.002). CONCLUSION: In the chronic stage of a
      myocardial infarction, restored T wave positivity predicts preserved systolic
      thickening, suggesting the presence of viable and normally contracting myocytes
      within the infarction area. Further studies are needed to establish the
      prognostic value of T wave characteristics in patients with a past history of
      myocardial infarction.

PMID- 11525072
TI  - Physical excercise and thrombotic risk in the elderly.
AB  - Aging increases certain thrombotic risk factors, such as fibrinogen, factor VII,
      PAI-1 and plasma viscosity, contributing to cardiovascular diseases being the
      principal cause of death in developed countries. Physical exercise can counteract
      this tendency by influencing such factors. PURPOSE: To assess the effect of
      regular physical exercise on fibrinogen, factor VII, PAI-1 and plasma viscosity
      in an elderly group. METHODS: Sixty-three old people of both sexes, aged between
      65 and 94, participated in this study, and were randomly distributed between a
      test group (n = 31) and a control group (n = 32). The test group followed a
      program of physical exercise for eight months, with an intensity of 60% to 80% of
      heart rate reserve, composed of three weekly sessions, on alternate days, of 60
      minutes each. The control group maintained their normal activity. Before the
      beginning of the program and eight months afterwards, blood samples were
      collected to assess fibrinogen, factor VII, PAI-1 and plasma viscosity. RESULTS:
      In the test group, fibrinogen, factor VII and plasma viscosity decreased
      significantly while PAI-1 showed no significant change. The control group did not
      present alterations in any of the parameters assessed. CONCLUSIONS: Regular
      physical exercise decreases thrombotic risk and may help to reduce cardiovascular
      events in the elderly.

PMID- 11525073
TI  - Atropine in exercise stress echocardiography? Case report.
AB  - Stress echocardiography is widely used in the investigation of coronary heart
      disease. Exercise stress echocardiography offers the advantage of visualizing
      myocardial motion abnormalities during physiological stress testing. The authors
      report the use of atropine, as an adjunct to exercise echocardiography, in risk
      stratification after myocardial infarction.

PMID- 11525074
TI  - [Congenital heart disease in adults. Part I. Non-cyanotic heart diseases].
AB  - Over the last decades major advances have been made in the diagnosis and
      treatment of congenital heart disease. Therefore, many children with simple and
      complex congenital heart defects can now survive to adulthood and represent an
      expanding population. Most of them are not "cured" and need specialized follow
      up. This two-part review presents the more common acyanotic and cyanotic
      congenital heart diseases that adult cardiologists are likely to face in their
      daily practice and discusses recent treatment advances.

PMID- 11525075
TI  - [Cardiac effects of acute poisoning with tricyclic antidepressants: systematic
      review of the literature. Part I].
AB  - Tricyclic antidepressant overdose is a frequent diagnosis in the emergency room.
      It is responsible for a significant percentage of hospital admissions for
      observation and treatment. This is due to its cardiac (as well as neurologic)
      toxicity, and the difficulty in predicting its clinical gravity. The authors
      present the paper with two objectives in mind: 1) information about a common and
      significant cardiological emergency; 2) presentation of the methodology
      concerning systematic reviews of the literature. In this first (of four)
      articles, the epidemiology tricyclic antidepressant overdose is presented. In the
      remaining three papers we will present its clinical presentation, diagnosis,
      treatment, prognosis and prevention. Note: this is the first of a series of four
      articles on the cardiac toxicity of tricyclic antidepressant overdose; the next
      three articles will be presented in the July, August and September issues of the
      RPC.

PMID- 11525076
TI  - A case of heart failure with an uncommon etiology.

PMID- 11525077
TI  - Reperfusion therapy for acute myocardial infarction with fibrinolytic therapy or
      combination reduced fibrinolytic therapy and platelet glycoprotein IIb/IIIa
      inhibition: the GUSTO V randomised trial.

PMID- 11525078
TI  - Integrating services for schizophrenia and substance abuse.
AB  - Over the past decade, several studies have attempted to determine whether
      integrating psychiatric and substance abuse treatment leads to better outcome for
      patients with comorbid schizophrenia and substance use disorders. A recent (1999)
      Cochrane Review (1) analyzed the effectiveness of prospective randomized studies
      of integrated treatment approaches, and concluded that there was no clear
      evidence for superiority of integrated treatment. This paper describes one such
      integrated treatment approach, in Beth Israel Medical Center's COPAD (Combined
      Psychiatric and Addictive Disorders) program. We summarize findings from an
      initial outcome study and a recent replication study; and describe clinical and
      research issues relevant to this population. Our data suggests the benefits of
      integrated treatment for patients with addictive disorders and schizophrenia, at
      least with regard to treatment retention. Clinical issues for such patients
      include identification of patients at risk, proper assessment and treatment
      planning, decision-making about mainstreaming vs. referral to specialized
      programs, and the importance of initial engagement and ongoing reengagement in
      successful treatment.

PMID- 11525079
TI  - The application of dialectical behavior therapy for patients with borderline
      personality disorder on inpatient units.
AB  - Inpatient treatment of individuals with borderline personality disorder (BPD) is
      typically fraught with difficulty and failure. Patients and staff often become
      entangled in intense negative therapeutic spirals that obliterate the potential
      for focused, realistic, and effective treatment interventions. We describe an
      inpatient treatment approach to BPD patients which is an application of
      Dialectical Behavior Therapy (DBT), a cognitive-behavioral therapy for patients
      with BPD which has been shown to be effective in reducing suicidal behavior,
      hospitalization, and treatment dropout and improving interpersonal functioning
      and anger management. The inpatient DBT staff creates a validating treatment
      milieu and focuses on orienting and educating new patients and identifying and
      prioritizing their treatment targets. Inpatient DBT treatment techniques include
      contingency management procedures, skills training and coaching, behavioral
      analysis, structured response protocols to suicidal and egregious behaviors on
      the unit, and consultation team meetings for DBT staff.

PMID- 11525081
TI  - The impact of racism on the delivery of health care and mental health services.
AB  - This article presents research findings useful in formulating a Best Practices
      Model for the delivery of mental health services to underserved minority
      populations. Aspects of the role of racism in health care delivery and public
      health planning are explored. An argument is made for inclusion of the legacy of
      the slavery experience and the history of racism in America in understanding the
      current health care crisis in the African-American population. The development of
      an outline in APA DSM IV for the use of cultural formulations in psychiatric
      diagnosis is discussed.

PMID- 11525080
TI  - Clinical management of neuroleptic malignant syndrome.
AB  - Neuroleptic malignant syndrome (NMS) continues to be an unpredictable and rare,
      but potentially fatal complication of antipsychotic medications. Presumptively
      linked to dopamine blockade, it nonetheless occurs in patients receiving newer
      atypical antipsychotics. The features of NMS, its pathophysiology, differential
      diagnosis, clinical course, risk factors, and morbidity and mortality are
      reviewed. Nonpharmacologic management centers on aggressive supportive care
      including vigilant nursing, physical therapy, cooling, rehydration,
      anticoagulation. Pharmacologic interventions include immediate discontinuation of
      antipsychotics, judicious use of anticholinergics, and adjunctive
      benzodiazepines. The utility of specific agents in actively treating NMS is
      reviewed. Bromocriptine and other dopaminergic drugs and dantrolene sodium have
      alternatively been considered without merit or efficacious. Guidelines for using
      these agents are presented. Electroconvulsive therapy, also somewhat
      controversial, is identified as a second line of treatment. Finally, management
      of the post-NMS patient is also reviewed.

PMID- 11525082
TI  - Stress and mood disorders during pregnancy: implications for child development.
AB  - Recent research suggests that stress, anxiety, and depression during pregnancy
      may have an impact on how the child develops. In this article, the central
      literature supporting this hypothesis is reviewed. Next, studies from our
      laboratory showing that differences in fetal heart rate patterns are associated
      with women's anxiety and depressive symptomatology are reviewed. The data
      indicate that we can detect fetal markers associated with alterations in women's
      mood that also are linked to differences in the neurobiological substrate of the
      fetus' emerging emotion regulation system. Identifying such fetal characteristics
      someday may contribute to the early detection and prevention of predispositions
      to childhood risk for emotional problems and even psychopathology.

PMID- 11525083
TI  - [Immunologic phenomena as the first sign of myelodysplastic syndrome].
AB  - Two patients, men aged 77 and 66 years, presented with a vasculitis. Due to an
      abnormal blood smear they were referred to the internist, who subsequently
      diagnosed a myelodysplastic syndrome (MDS). They were initially treated with a
      high dose of corticosteroids and this dosage later became a maintenance dose.
      Immunological phenomena occur in 10-14% of MDS patients and seem to have a poor
      prognosis. Most patients respond well to treatment with corticosteroids.
      Occasionally, favourable haematological responses to corticosteroid therapy are
      seen, although this was not the case in the two patients described. When patients
      present with an immunological disorder, such as a vasculitis or an autoimmune
      disease, it is important to be aware of the possibility of an underlying MDS.

PMID- 11525084
TI  - [Term breech presentation: an indication for cesarean section].
AB  - The results of the 'Term breech trial' (carried out at 121 centres in 26
      countries, and in which 2088 women with a singleton foetus in breech presentation
      were randomly assigned to planned caesarean section or planned vaginal birth)
      indicate that in countries with low perinatal mortality rates, planned vaginal
      birth was associated with serious neonatal morbidity at least 12.5 times more
      often than was the case for planned caesarean section. The trial is
      methodologically sound. Unfortunately, no information on long-term neonatal
      morbidity is provided and the study is too small to assess maternal mortality.
      Moreover, the study provides no information on the consequences of a uterine scar
      for future pregnancies. However, as there are no other data from studies in the
      Netherlands, the results from this trial also have a bearing on Dutch practice.
      The pregnant mother of a term breech baby should be carefully informed about the
      results of this trial, prior to the preferred means of delivery being decided
      upon in consultation with her. A deliberate choice for an elective caesarean
      section based on a mere breech presentation is justified.

PMID- 11525085
TI  - [Treatment of diabetes mellitus type 2 in family practice].
AB  - In the care of type 2 diabetes mellitus, a combined approach is required to
      address the risk factors for micro- and macrovascular complications. In the
      Netherlands, type 2 diabetes care is mainly provided by the general practitioner
      (GP). GP care is often not provided in accordance with the guidelines, and the
      strict targets for glycaemic, blood pressure and lipid control are often not
      achieved. Therefore, the GP should be supported in the provision of diabetes
      care. GP support in providing diabetes care can range from the organisation of
      care within the individual GP practice, through to support from an organisation
      within primary care or to 'shared care' with a hospital in secondary care. There
      is still scarce scientific evidence for the effectiveness of models for the
      organisation of diabetes care in primary care in the Netherlands. Scientific
      research into the effectiveness and cost-effectiveness is necessary before models
      for the organisation of diabetes care in primary care can be widely implemented
      and structurally financed.

PMID- 11525086
TI  - [The thiazolidinedione derivates: a new class of oral blood glucose lowering
      agents].
AB  - The thiazolidine-dione derivatives are a new class of oral blood-glucose lowering
      drugs in type 2 diabetes. They increase the sensitivity of target tissues to
      insulin, thereby reducing insulin resistance. They act by activation of a
      specific nuclear receptor--the peroxisome proliferator-activated receptor gamma
      (PPAR-gamma)--which increases transcription of certain genes involved in
      adipocyte differentiation and lipid and glucose metabolism. They increase glucose
      disposal, reduce hepatic glucose output and reduce both plasma glucose and
      circulating insulin. By reducing insulin requirements the hypersecretion of the
      beta cell can be diminished, thereby sparing beta cell function. Thiazolidine
      dione derivatives reduce plasma glycosylated haemoglobin (HbA1c) by about 1 to
      2%. Combination therapy with sulphonylurea derivatives or metformin seems to be
      more effective, i.e. lower dosages of either agent or both are sufficient to
      achieve the same reduction in plasma glucose and HbA1c as monotherapy. The
      thiazolidine-dione derivatives are generally well tolerated and the new drugs
      such as rosiglitazone and pioglitazone do not seem to be associated with
      idiosyncratic hepatotoxicity.

PMID- 11525087
TI  - [Repaglinide, potentially a therapeutic improvement for diabetes mellitus type
      2].
AB  - In about 25% of type 2 diabetes patients, good diabetes control is not attainable
      with oral blood-glucose lowering drugs. Furthermore, in many people with diabetes
      the disease deteriorates, despite the use of blood-glucose lowering medication,
      due to the decline of the pancreatic beta cells. The development of new drugs,
      such as repaglinide, is therefore important. Repaglinide is an insulin secretion
      enhancer with a different mechanism of action to the sulphonylureas, which means
      it does not continuously stimulate insulin secretion. The tablets should be taken
      with each meal. After oral ingestion repaglinide is resorbed quickly, with a half
      life of between 30 minutes to an hour. In clinical trials repaglinide has been
      found to be equally effective as glibenclamide. Repaglinide has been found to be
      particularly effective in sulphonylurea-naive patients. Skipping the meal plus
      tablet combination results in less frequent hypoglycaemic symptoms compared to
      glibenclamide. Repaglinide results in greater reductions in postprandial glucose
      levels than glibenclamide. It does not affect insulin resistance. Long-term data
      are lacking, both with regard to efficacy and side effects. Repaglinide deserves
      a place in the diabetes treatment of newly-diagnosed type 2 diabetes patients who
      are well-informed about their disease, as well as in patients with renal failure.
      It should also be considered for patients whose diabetes is poorly controlled on
      metformin monotherapy.

PMID- 11525088
TI  - [Diagnostic image (50) Positive Pemberton's sign].
AB  - A 32-year-old woman had a progressive euthyroid goitre and dyspnoea. Pemberton's
      sign was found to be positive: elevation of both arms resulted in an inspiratory
      stridor and venous congestion. Symptoms and signs resolved after total
      thyroidectomy.

PMID- 11525089
TI  - [From gene to disease; deletion of the DAZ-gene from the Y-chromosome in oligo-
      or azoospermia ].
AB  - DAZ gene deletions at the azoospermia factor (AZF) locus on the Y chromosome,
      have been implicated as one of the major causes of idiopathic male subfertility.
      Deletions of the entire DAZ gene have been reported in azoospermia as well as in
      oligozoospermia. The DAZ gene encodes a RNA binding protein which is expressed
      exclusively in germ cells. The exact biological role and function of the DAZ
      protein has yet to be resolved.

PMID- 11525090
TI  - [Neonatal outcome after a planned vaginal breech birth: no association with
      parity or birth weight, but more birth injuries than in planned cesarean
      section].
AB  - OBJECTIVE: To investigate if in a planned vaginal breech delivery parity or
      birthweight is associated with neonatal outcome. DESIGN: Retrospective analysis
      of local data from the National Obstetric Registration of the Netherlands.
      METHOD: The study concerned outcomes of 516 births of singletons with breech
      presentation after pregnancies > 37 weeks in the period 1 January 1995 to 31
      December 1999 at the Medical Centre Leeuwarden, the Netherlands; there were 448
      planned vaginal breech deliveries. Nulliparous and multiparous were separately
      studied in four birthweight groups (< 3000 g, 3000-3499 g, 3500-3999 g and > or =
      4000 g). RESULTS: None of the neonates born by primary caesarean experienced
      birth trauma. In the group with planned vaginal breech delivery 2% of the
      neonates of nulliparous and 3% of multiparous mothers experienced neonatal
      morbidity. There was one case of perinatal mortality due to birth trauma (0.2%).
      The total perinatal morbidity was 6% with no differences between nulliparae and
      multiparae and between the birthweight groups. In nulliparous, the percentage of
      emergency caesarean sections rose from 20% in the < 3000 g birthweight group to
      62% in the > or = 4000 g birthweight group. CONCLUSION: Following a planned
      vaginal breech delivery, no differences were observed in neonatal outcome between
      nulliparous and multiparous women and between the four birthweight groups. The
      extent to which the figures were influenced by the selection for primary
      caesarean section is not clear.

PMID- 11525091
TI  - [More moderate neonatal morbidity in the case of non-randomized vaginal delivery
      of term breech pregnancies].
AB  - OBJECTIVE: To compare the outcome of term breech pregnancies by planned caesarean
      section or by planned vaginal delivery at the Department of Obstetrics and
      Gynaecology, Atrium Medisch Centrum Heerlen, the Netherlands, with the findings
      in the so-called 'Term breech trial' (TBT). DESIGN: Randomised and descriptive
      non-randomised clinical trial. METHOD: During the period of participation in the
      TBT prospective data were collected on all deliveries of a term baby in breech
      presentation. The pregnant women who were included in the TBT (n = 35) were
      randomised in a planned caesarean section (CS) group and a planned vaginal
      delivery (VD) group. All women with a child in term breech presentation who did
      not join the trial constituted the non-randomised group (n = 201) and were
      divided in a primary CS group (n = 48) and a started VD group (n = 153). Neonatal
      and maternal mortality and morbidity were analysed according to the intended mode
      of delivery. RESULTS: Neither neonatal nor maternal mortality occurred in any of
      the groups. No significant differences in serious neonatal and maternal morbidity
      were observed between both subgroups in either the randomised or non-randomised
      group. However, in the non-randomised group who were allowed to start a vaginal
      delivery, moderate neonatal morbidity was significantly higher (25/153) than in
      the primary CS group (2/48). CONCLUSION: The differences in serious neonatal
      morbidity as observed in the TBT were not confirmed in this study. However, there
      were disadvantageous differences in the moderate neonatal morbidity for the non
      randomised group who were allowed to start a vaginal delivery. In addition to the
      TBT results, these findings might be discussed with women with a term breech
      presentation.

PMID- 11525092
TI  - [Abdominal pain and vomiting: a 4-year old boy with relaxation of diaphragm].
AB  - A 4-year-old boy presented with vomiting, abdominal pain and a visible swelling
      on the left side of the upper abdomen. He had been generally unwell for a week,
      and had been suffering from constipation for a longer period of time.
      Radiological examination revealed a large space containing air and fluid in the
      left side of the upper abdomen and the chest region. During surgery, gastric
      volvulus and an elevated diaphragm were found. Plication of the diaphragm was
      performed, and the intra-abdominal organs were replaced in their correct
      positions. Patient recovered well and remained without complaints. Diaphragm
      relaxation is rare, and can be either congenital or acquired. Unlike congenital
      diaphragmatic hernia, diaphragm relaxation is characterised by an elevated
      diaphragm which, although intact, is hypoplastic.

PMID- 11525093
TI  - [With an eye on the vocal cords; family practice and hoarseness]].

PMID- 11525094
TI  - [National hepatitis B vaccination closer to implementation, but not soon enough:
      recommendations from the Dutch Health Council].

PMID- 11525095
TI  - [CBO guideline 'Deep venous thrombosis and pulmonary embolism'; revision of
      earlier guidelines].

PMID- 11525096
TI  - [Herbal remedies in veterinary phytotherapy].
AB  - Phytotherapy is based on the use of herbal remedies (phytopharmaceuticals) for
      therapy and prophylactic measures of illness in humans and animals. Animal owners
      as well as veterinarians (surgeons) are more and more interested in veterinary
      phytotherapy. The following review explains fundamentals of veterinary
      phytotherapy as well as the production, application and possible side-effects of
      veterinary herbal remedies (veterinary phytopharmaceuticals).

PMID- 11525097
TI  - [Muscle biopsy using the muscle punch--removal technique, transport and
      evaluation ability].
AB  - Histopathological striated muscle examination is one of the most important and
      sensitive tests in diagnosis of muscle and/or nerve diseases. Although muscle
      biopsy is a relatively easy procedure, it is not frequently performed in small
      animal practice conditions. Different biopsy techniques have been described in
      veterinary literature. Punch biopsy of striated muscle appears to be a less
      invasive and quicker method in comparison with traditional surgical excision
      technique. Additionally, punch biopsy provide good quality and adequate amount of
      muscle tissue for diagnostic histopathological evaluation. The aim of this study
      is to describe striated muscle punch biopsy technique and to encourage use of it
      under the conditions of small animal practice. The described biopsy method can be
      specially advantageous in screening of inherited muscle diseases in affected
      litters or even wider animal population.

PMID- 11525098
TI  - [Avian leukosis subgroup J in broiler breeders in Switzerland].
AB  - Since a new envelope subgroup (J) of the avian leukosis-sarcomatosis-complex was
      isolated for the first time from broiler breeders in the United Kingdom in 1989
      and was characterized and associated with myeloid leukosis (syn.
      myelocytomatosis) the emergence of this subgroup was reported from all over the
      world. Thus the first known case of subgroup J avian leukosis in Switzerland in
      four imported broiler breeder flocks will be described. A total of 53 broiler
      breeder birds from four flocks showing reduced performance and increased
      mortality were submitted for postmortem examination. Approximately 20 blood
      samples from each flock were monitored serologically for antibodies against avian
      leukosis virus subgroup J (ALV-J). On necropsy myeloid leukosis (ML) was
      diagnosed in all four flocks. Furthermore the blood samples of three flocks
      showed significant ELISA-titres for ALV-J.

PMID- 11525099
TI  - Paradoxical vestibular disease with trigeminal nerve-sheath tumor in a dog.
AB  - A thirteen-year old spayed female poodle was referred because of atrophy of
      temporal and masseter muscles on the left and head tilt and episodical circling
      to the right side. Additionally, decreased facial sensation, absent menace
      reaction, palpebral and corneal reflexes on the left side, as well as ipsilateral
      hemiparesis and tongue palsy were noticed. Generalised vestibular ataxia and
      hypermetria in the front limbs were present. Based on the clinical signs, the
      presumptive anatomical localization of the lesion was the cerebellopontine angle
      including parts of the caudal brainstem with involvement of the trigeminal,
      facial and hypoglossal nerves. Involvement of either flocculonodular lobe or the
      caudal cerebellar peduncle on the left side causing paradoxical vestibular
      disease was suspected. On magnetic resonance imaging a large enhancing lesion in
      the area of the left cerebellopontine angle involving the trigeminal nerve and
      compressing cerebellum and brainstem was seen. Because of the poor prognosis the
      dog was euthanized on the owner's request. This space occupying lesion could be
      identified as a trigeminal neurofibrosarcoma/schwannoma on post mortem
      histopathological examination.

PMID- 11525100
TI  - The uneven landscape of newborn intensive care services: variation in the
      neonatology workforce.
AB  - CONTEXT: In the past 30 years, the number of neonatologists has increased while
      total births have remained nearly constant. It is not known how equitably this
      expanded workforce is distributed. OBJECTIVE: To determine the geographic
      distribution of neonatologists in the United States. DATA SOURCES: 1996 American
      Medical Association physician masterfiles; 1999 survey of all U.S. neonatal
      intensive care units; 1995 American Hospital Association hospital survey; and
      1995 U.S. vital records. MEASURES: The number of neonatologists and neonatal mid
      level providers per live birth within 246 market-based regions. RESULTS: The
      neonatology workforce varied substantially across neonatal intensive care
      regions. The number of neonatologists per 10,000 live births ranged from 1.2 to
      25.6 with an interquintile range of 3.5 to 8.5. The weakly positive correlation
      between neonatologists and neonatal mid-level providers per live birth is not
      consistent with substitution of neonatal mid-level providers for neonatologists
      (Spearman rank-correlation coefficient, 0.17; P < 0.01). There was no difference
      in the percentage of neonatal fellows in the lowest and highest workforce
      quintile (14% vs. 16%) or in the percentage of neonatologists engaged
      predominantly in research, teaching, or administration (14% in lowest and highest
      quintiles). CONCLUSIONS: The regional supply of neonatologists varies
      dramatically and cannot be explained by the substitution of neonatal mid-level
      providers or by the presence of academic medical centers. Further research is
      warranted to understand whether neonatal intensive care resources are located in
      accordance with risk and whether more resources improve newborn outcomes.

PMID- 11525101
TI  - Meta-analysis of dietary restriction during fecal occult blood testing.
AB  - CONTEXT: Dietary restriction is often recommended during fecal occult blood
      testing (FOBT) as a means of increasing test accuracy, but concern surrounds
      whether such restriction also reduces the chance that patients will complete the
      test. PURPOSE: We conducted a systematic review and meta-analysis to determine if
      advice about dietary restrictions affects the rate of completion of FOBT and the
      rate of positive results. METHODS: We searched the MEDLINE database and hand
      searched the bibliographies of other systematic reviews and clinical practice
      guidelines to identify randomized trials of advice to perform dietary restriction
      during FOBT. We included only trials that reported the proportion of patients who
      completed the occult blood tests (completion rate). When such information was
      available, we also recorded the proportion of patients who had positive test
      results (positivity rate). RESULTS: Five randomized trials met our inclusion
      criteria. All used guaiac-based Hemoccult tests; none reported results from
      rehydrated test slides. In four trials, there was little or no difference in test
      completion between patients assigned to dietary restriction and those with no
      restriction. In one small trial that used an especially restrictive diet,
      completion was 21 percentage points lower in the restricted group. Positivity
      rates were reported in four trials, none of which found a statistically
      significant difference between groups. Meta-analysis showed no difference in the
      summary positivity rate between those assigned to dietary restriction versus
      those not restricted (difference in positivity rate, 0%; 95% CI, -1% to 1%).
      CONCLUSIONS: Available data suggest that advice to perform modest dietary
      restriction during unrehydrated FOBT does not affect the completion rate, but
      more severe restrictions may. Dietary restriction also does not appear to affect
      positivity rates. On the basis of these data, physicians do not need to advise
      patients to restrict their diet for nonrehydrated FOBTs.

PMID- 11525102
TI  - Taking advantage of the explosion of systematic reviews: an efficient MEDLINE
      search strategy.
AB  - CONTEXT: Systematic reviews of the literature are an important resource for
      clinicians. Unfortunately, the few published strategies for identifying these
      articles involve MEDLINE interfaces not widely available outside of academic
      medicine. In addition, the performance of these strategies is unknown. OBJECTIVE:
      To develop and evaluate a search strategy for identifying systematic reviews by
      using a publicly available MEDLINE interface (PubMed). DESIGN: Diagnostic test
      assessment. DEFINITION OF SENSITIVITY: The proportion of recognized systematic
      reviews (indexed in the Cochrane Library's Database of Abstracts of Reviews of
      Effectiveness [DARE] or in ACP Journal Club) that are identified by the search
      strategy. DEFINITION OF POSITIVE PREDICTIVE VALUE: The proportion of articles
      identified in one of three sample searches (screening for colorectal cancer,
      thrombolytic therapy for venous thromboembolism, and treatment of dementia) that
      meet a minimum definition of systematic review. RESULTS: Our PubMed search
      strategy identified 93 of 100 DARE-indexed systematic reviews, a sensitivity of
      93% (95% CI, 86% to 97%). For the sample of systematic reviews drawn from ACP
      Journal Club (n = 103), the PubMed strategy achieved a sensitivity of 97% (CI,
      91% to 99%). When the three sample search strings were used, approximately 50% of
      retrieved articles met our minimum definition of systematic review. In contrast,
      the similar precision of a PubMed search restricted to review-type articles (as
      indexed by MEDLINE) was less than 10%. CONCLUSIONS: This search strategy
      identified most systematic reviews without over-whelming users with numerous
      false-positive results. A "single-click" filter based on this strategy is now
      available as part of the Clinical Queries feature of PubMed.

PMID- 11525103
TI  - Effectiveness of an intervention to improve primary care provider recognition of
      depression.
AB  - CONTEXT: Depression remains under-recognized and undertreated by primary care
      providers. While systematic screening has the potential to improve recognition,
      providers may overlook screening results because of barriers to accessing the
      information and the need to address multiple health care issues. OBJECTIVE: To
      determine whether limited follow-up of positive findings on depression screening
      improves provider recognition and initial management of depression. DESIGN:
      Before-after study. PATIENTS: Consecutive patients with positive findings on
      depression screening in a Veterans Affairs primary care clinic in Oregon during
      the 3 months before (n = 160) and the 3 months after (n = 97) the intervention
      began. INTERVENTION: Patients with positive findings on depression screening
      completed a self-administered questionnaire (Patient Health Questionnaire), which
      they turned in to their provider. A mental health nurse subsequently reviewed the
      records of patients who completed questionnaires and contacted providers when
      depression was not mentioned in the visit note. OUTCOME MEASURES: Documentation
      of depression or suicidal ideation and actions taken for depression (prescription
      of antidepressant medication, mental health referral, watchful waiting) at the
      clinic visit. RESULTS: The mental health nurse received questionnaires for only
      39 (40%) postintervention patients. Documentation of depression symptoms (72% vs.
      48%; P < 0.001) and suicidal ideation (36% vs. 14%; P < 0.001) significantly
      improved in the postintervention group compared with the preintervention group.
      Postintervention patients were also more likely to begin receiving
      antidepressants (23% vs. 12%; P < 0.05) and to be referred for mental health
      services (28% vs. 9%; P < 0.001). CONCLUSION: A limited intervention can improve
      provider recognition and initial management of depression in a Veterans Affairs
      primary care setting.

PMID- 11525104
TI  - Operative mortality with elective surgery in older adults.
AB  - CONTEXT: For patients considering elective major surgery, information about
      operative mortality risks is essential for careful decision making. Because
      available information is often limited to educated guesses or optimistic data
      from case series, we examined surgical mortality by using nationwide data.
      PRACTICE PATTERN EXAMINED: Operative mortality in 1.2 million patients in the
      Medicare system who were hospitalized between 1994 and 1999 for major elective
      surgery (six cardiovascular procedures and eight major cancer resections). DATA
      SOURCE: MEDPAR file of the National Medicare claims database for patients 65
      years of age and older. OUTCOMES: Operative mortality, defined as death within 30
      days of the operation or death before discharge. RESULTS: Overall operative
      mortality varied widely according to procedure. Procedures associated with
      relatively low mortality risk included carotid endarterectomy (1.3%) and
      nephrectomy (2.3%). Overall mortality was greater than 10% for other procedures,
      such as mitral valve replacement (10.5%), esophagectomy (13.6%), and
      pneumonectomy (13.7%). In general, mortality risk increased with age. Operative
      mortality for patients 80 years of age and older was more than twice that for
      patients 65 to 69 years of age. CONCLUSION: Population-based operative mortality
      for major surgery varies by procedure and patient age and is considerably higher
      than that typically reported in case series and trials.

PMID- 11525105
TI  - Neonatal workforce: how much is enough?

PMID- 11525107
TI  - Primer on statistical significance and P values.

PMID- 11525106
TI  - Diet for fecal occult blood test screening: help or harm?

PMID- 11525108
TI  - Sensationalism in the media: when scientists and journalists may be complicit
      collaborators.

PMID- 11525109
TI  - Does measuring fructosamine help patients with diabetes?

PMID- 11525110
TI  - [Changes in serum malondialdehyde-modified low-density lipoprotein in patients
      with acute myocardial infarction and stable angina pectoris treated by coronary
      angioplasty].
AB  - OBJECTIVES: Serum malondialdehyde-modified low-density lipoprotein(MDA-LDL) was
      measured as a marker of oxidative stress, and the changes in serum MDA-LDL
      compared in patients with acute myocardial infarction and stable angina pectoris
      treated by percutaneous transluminal coronary angioplasty (PTCA). METHODS: Forty
      one patients with acute myocardial infarction or stable angina pectoris were
      admitted to our hospitals between January 2000 and June 2000. Direct PTCA was
      performed in 17 patients(MI group) and elective PTCA in 24 patients(AP group).
      Coronary angiography was performed in nine control subjects(control group). Serum
      MDA-LDL was measured in the peripheral venous blood before and immediately after
      procedures in each group(normal range 20-80 U/l). RESULTS: There were no
      significant differences in patient characteristics, except age, between the MI
      group and AP group. Serum MDA-LDL was elevated above the normal range before the
      procedure in both groups(MI group 104.7 +/- 52.0 U/l, AP group 99.7 +/- 42.8
      U/l), and significantly decreased immediately after the procedure(MI group 61.3
      +/- 25.6 U/l, AP group 62.0 +/- 29.6 U/l), but there were no significant
      differences between the two groups. Serum MDA-LDL was elevated before the
      procedure (99.3 +/- 48.9 U/l) in the control group and significantly decreased
      immediately after the procedure(61.7 +/- 26.2 U/l). However, these values did not
      differ from the values before and immediately after the procedure in the MI group
      and the AP group. The percentage changes in serum MDA-LDL before and immediately
      after the procedure were -38 +/- 16% in the MI group, -37 +/- 17% in the AP group
      and -36 +/- 20% in the control group, and there were no significant differences
      between the three groups. CONCLUSIONS: No significant difference in the changes
      in serum MDA-LDL was observed between patients with acute myocardial infarction
      and stable angina pectoris treated by PTCA. However, anticoagulants may affect
      the MDA-LDL measurements directly, because similar changes in serum MDA-LDL were
      observed in control subjects after only coronary angiography.

PMID- 11525111
TI  - [Clinical significance of plasma atrial and brain natriuretic peptide levels
      during hemodialysis in hemodialysis patients with old myocardial infarction].
AB  - OBJECTIVES: The plasma levels of atrial natriuretic peptide(ANP) and brain
      natriuretic peptide(BNP) are useful to evaluate left ventricular function in
      patients with old myocardial infarction(OMI). This echocardiographic study
      examined the clinical importance of the measurement of ANP and BNP in patients
      with OMI undergoing hemodialysis. METHODS: ANP and BNP levels were measured
      before and after hemodialysis in 36 patients with OMI and 42 patients without
      ischemic heart disease as controls(control group). Echocardiography was performed
      after hemodialysis. The patients with OMI were classified into two groups
      according to left ventricular percentage fractional shortening(% FS): Normal(OMI
      N) group with %FS > or = 30%(n = 19) and low (OMI-L) group with %FS < 30%(n =
      17). RESULTS: The ANP, BNP levels and BNP/ANP ratio before and after hemodialysis
      were significantly higher in the OMI-L group than in the other groups. BNP level
      was significantly inversely correlated with %FS(r = -0.60, p < 0.05) and
      correlated with E wave and E/A, in mitral inflow only in the OMI-L group. The
      decrease in BNP level during hemodialysis was significantly greater in the OMI-L
      group than in the other groups, but not in ANP level. CONCLUSIONS: These findings
      suggest that ANP and BNP levels are increased in patients with left ventricular
      dysfunction undergoing hemodialysis compared to those with normal left
      ventricular function. ANP level is convenient for decision of suitable dry
      weight. In contrast, BNP level that correlated inversely with impairment of left
      ventricular function is a more sensitive index of left ventricular function than
      ANP in patients with OMI undergoing hemodialysis.

PMID- 11525112
TI  - [Complications of stress echocardiography].
AB  - BACKGROUND: Stress echocardiography is an established clinical testing method and
      is accurate for the detection of coronary artery disease. Despite its widespread
      use, the safety of stress echocardiography has not been sufficiently documented
      in Japanese laboratories. OBJECTIVES: The feasibility, safety, complications and
      side effects of stress echocardiography were assessed for detecting myocardial
      ischemia in patients with suspected coronary artery disease. METHODS: 1,866
      patients who underwent dobutamine echocardiography(n = 897), exercise
      echocardiography(n = 722), and dipyridamole echocardiography(n = 247) were
      prospectively studied from November 1990 to April 2000. Dobutamine was
      administered intravenously at 5, 10, 20, 30, 40 micrograms/kg/min in 3-minute
      intervals. Exercise echocardiography used the supine ergometer, starting at 50 W
      and increasing gradually by 25 W at 3-minute intervals to the maximum of 150 W.
      Dipyridamole was administered intravenously at 0.14 mg/kg/min for 4 min. After a
      4-minute observation period, the drug was re-administered at the same dose for 2
      min. RESULTS: The most common side effects under each stress were ventricular
      premature beats in 34.1% (dobutamine echocardiography), ventricular premature
      beats in 14.4%(exercise), and headache in 24.3% (dipyridamole). Serious side
      effects occurred in one patient(0.05%). The case of acute myocardial infarction
      was caused by dipyridamole echocardiography, and the patient needed emergency
      coronary angioplasty. Seven patients needed other drug therapy for nonsustained
      ventricular tachycardia(one), paroxysmal supraventricular tachycardia(two), sinus
      bradycardia(three), and bronchial asthma(one). There was no incidence of death,
      shock, or ventricular fibrillation, sustained ventricular tachycardia or other
      conditions requiring inpatient observation during stress echocardiography.
      CONCLUSIONS: Stress echocardiography is a reasonable, safe method for determining
      myocardial ischemia, but may be associated with minor, self-limiting side
      effects.

PMID- 11525113
TI  - [Effects of home oxygen therapy on patients with chronic heart failure].
AB  - OBJECTIVES: Dyspnea on exertion and/or hypoxemia due to nocturnal respiratory
      disturbance may occur in patients with stable chronic congestive heart failure.
      Such patients with respiratory disorder during sleep have a poor prognosis. The
      effects of treatment with home oxygen therapy on patients with congestive heart
      failure are unclear when symptoms are stable at rest. This study investigated the
      effects of home oxygen therapy on patients with stable chronic congestive heart
      failure. METHODS: Thirty-three patients with stable chronic congestive heart
      failure(New York Heart Association functional class II-IV) and hypoxemia during
      exercise or sleep were treated with oxygen above the level of 90% SaO2. The
      following factors were compared before and after home oxygen therapy: Subjective
      minimal capacity on exercise(metabolic equivalents: METs) before and 1 month
      after patients first became aware of dyspnea on effort using the specific
      activity scale(SAS); SaO2 at rest before and 1 month after; and frequency of
      admission during 1 year due to deterioration of heart failure. RESULTS: After
      home oxygen therapy, SAS improved from 2.5 +/- 0.9 to 3.3 +/- 1.0 METs(p <
      0.0001), and SaO2 at rest improved from 92.8 +/- 2.5% to 96.3 +/- 1.6%(p <
      0.0001). The frequency of admission was decreased from 1.3 +/- 1.2 to 0.8 +/- 1.2
      times(p = 0.03). CONCLUSIONS: Home oxygen therapy is effective for improving the
      symptoms and activity of daily life in patients with chronic heart failure. Home
      oxygen therapy may prevent the deterioration of heart failure.

PMID- 11525114
TI  - [Survival after oozing type cardiac rupture associated with subepicardial
      aneurysm evaluated by echocardiography: a case report].
AB  - A 64-year-old woman was admitted to our hospital with acute myocardial
      infarction. She underwent emergent percutaneous transluminal coronary
      angioplasty. Transthoracic echocardiography revealed mild pericardial effusion on
      the third day. Pericarditis or cardiac rupture were suspected, so transthoracic
      echocardiography was repeated serially. On the sixth day, transthoracic
      echocardiography showed increasing pericardial effusion and abrupt interruption
      of the apical myocardium of the left ventricle and intact epicardial imaging with
      systolic expansion. The diagnosis was oozing type cardiac rupture of a
      subepicardial aneurysm. Surgical treatment was successful and the accuracy of the
      echocardiographic diagnosis was established.

PMID- 11525115
TI  - Arrhythmogenic right ventricular dysplasia presenting as regression of left
      ventricular dysfunction: a case report.
AB  - Arrhythmogenic right ventricular dysplasia is considered to be a slowly
      progressive disease in which left ventricular dysfunction and congestive heart
      failure usually appear at the end stage. The initial clinical presentation of
      this 56-year-old Japanese woman was left-sided heart failure, and the diagnosis
      was dilated cardiomyopathy, but her left ventricular size and ejection fraction
      regressed during 10 years of treatment, whereas her right ventricular parameters
      showed no change.

PMID- 11525116
TI  - [A 59-year-old man with lower abdominal pulsatile mass. Iliac anastomotic
      aneurysms].

PMID- 11525117
TI  - [A biological model of accelerated aging. III. Histological characteristics of
      age-related changes of spermatogenic epithelium in mice SAM (senescence
      accelerated mouse)].
AB  - The data characterizing the age-related morphological changes in the
      spermatogenic epithelium of SAMP1 (senescence-accelerated prone) and SDAMR1
      (senescence-accelerated resistant) mice are presented. In many tubules, "early
      spermatogenesis" was accompanied by the formation of many morphologically
      abnormal germ cells on histological sections of the gonads of sexually immature
      (three-four weeks) mice of both strains. At this stage, destructive processes in
      the spermatogenic epithelium were more pronounced in SAMR1 mice. In sexually
      mature (two-three months) SAMP1 and SAMR1 mice, spermatogenesis as a whole
      proceeded normally. The first signs of regressive changes in the inner structure
      of most tubules (disintegration, detachment of spermatogenic epithelium from
      basal membrane) and morphology of germ cells (pycnosis, nuclear and cytoplasmic
      vacuolization) were found in SAMP1 mice at the age of six-seven months. In the
      older age groups (9-10 and 12-15 months), all types of spermatogenic cells were
      represented in both SAMP1 and SAMR1 mice, but most of these cells were atypical.
      Mitotic figures were recorded in a population of highly differentiated Sertoli
      cells.

PMID- 11525118
TI  - [Composition of neutrophil peroxisomes].
AB  - Peroxisomes of neutrophils are formed in promyelocytes. In addition to
      myeloperoxidase constituting 35% peroxisomes, they contain nonenzymatic
      antimicrobial cationic peptides and polypeptides, several serine proteases, as
      well as some other hydrolases and additional components. Similar to serine
      proteases, these hydrolases can serve as natural antibiotics. Their function can
      complement the main oxidation function of neutrophilic myeloperoxidase in the
      protective response. The peroxisomes contain acid glycosaminoglycans functioning
      as an anionic carrier that reversibly binds cationic proteins, including
      hydrolases.

PMID- 11525119
TI  - [Regularity of biochemical differentiation in ontogenesis].
AB  - Here we review original data on biochemical differentiation mechanisms. The
      patterns of the preprogrammed metabolism of the embryo are studied by comparing
      biochemical mechanisms in undifferentiated embryonic tissues in the course of
      differentiation and during the terminal establishment of a specialized tissue.
      This review is composed of three main sections corresponding to the specificity
      of biochemical differentiation. The first section covers the material on time
      related isozyme pattern during skeletal muscle differentiation in a loach (a
      teleostean fish). The second section presents the data on "incorporated
      activation", i.e., the appearance of a functional relationship between
      contractile proteins biosynthesis and the systems of glycogenolysis and glycogen
      synthesis during the development of chick embryo muscle. The third section covers
      the data on liver differentiation, the formation of the glycogen organelle with
      embedded enzymes of glycogen synthesis, and degradation during the development of
      chick and rat embryos.

PMID- 11525120
TI  - [ A long-term changes of macro- and microelement balance in blood serum, its
      ultrafiltrates and hairs after exposure to low doses of ionizing radiation].
AB  - Using inductively coupled plasma atomic emission spectrometry, we examined the
      level of Al, Cd, Co, Cu, Fe, Mg, Mo, P, Pb, S, and Zn in blood serum, its
      ultrafiltrates, and hairs of liquidators of the Chernobyl Nuclear Power Plant
      accident who were working in the disaster region in 1986-1987. Studies continued
      over a period of time provided evidence for a distinct change in the balance of
      macroelements and trace elements in the studied biological substrates of
      irradiated individuals. An increase in the level of copper in the ultrafiltrate
      and a marked decrease in the content of zinc in the ultrafiltrate are viewed as
      key factors in the generation of a response to low doses of ionizing radiation.
      Concerning the content of iron in hairs, we demonstrate its accelerated removal
      from the body of liquidators. The altered balance of biotic macroelements,
      phosphorus, and sulfur remained unchanged when these characteristics were studied
      as a function of time. We found changes in the ratios of divalent cations,
      magnesium and zinc, in the ultrafiltrates. The magnesium concentration in the
      studied biological substrates was the most stable characteristic after
      irradiation. The level of toxic trace elements (lead, cadmium, and aluminum) did
      not exceed physiologically acceptable levels, while their content in hairs may be
      a biological indicator of their accumulation in the body.

PMID- 11525121
TI  - [Micronucleus frequency is increased in bone marrow erythrocytes from offspring
      of male mice exposed to chronic low-dose gamma irradiation].
AB  - The micronucleus frequency in bone marrow erythrocytes from the F1 progeny of
      male mice exposed to chronic low-dose gamma-irradiation was determined. Male
      BALB/c mice were irradiated with 10, 25 and 50 cGy at dose rates of 1, 5, and 15
      cGy/day and mated with unirradiated females on day 15 after irradiation. The
      obtained offspring had an elevated micronucleus frequency in bone marrow
      erythrocytes at the age of 2 months. This suggests the transmission of genome
      instability from damaged germ-line cells of irradiated male parents to somatic
      cells of the progeny.

PMID- 11525122
TI  - [Characteristics of halo formation during pathogenesis as a response of cereal
      epidermal cells to penetration of powdery mildew pathogens].
AB  - A cytophysiological study was carried out of the functional status of a halo as a
      response of the host plant to contact with a powdery mildew pathogen.
      Interactions of the powdery mildew causative agents with barley, wheat, wheat
      wheat-grass hybrids, wheat-aegilops lines, and aegilops with different genotypic
      resistance lead to the expression of haloes during pathogens, which are induced
      by infection pegs of the primary growth tubes appressoria, and hyphal lobes.
      Haloes are visualized using cytochemical reactions to proteins and scanning
      electron microscopy. The observed differences in the size of haloes and intensity
      of their staining (uniform or zonal) are related, to a great extent, to
      individual reactions of the plant cell at the penetration site and, to a lesser
      extent, to the level of genotypic resistance. An analysis of electron microscopy
      and cytochemistry studies suggests that the halo as a physiologically active zone
      is localized at the level of the plant cell plasmalemma. Active taxis of the cell
      organelles to the site of infection during the formation of a halo suggests that
      some kind of informational signals to changes in the cell metabolism are spread
      from the halo zone, which lead to compatible or incompatible interactions.

PMID- 11525123
TI  - [Level of cytokines, abscisic and salicylic acids in the leafs of Phlox under the
      effect of invasion by conidia of phytopathogens].
AB  - We studied the effects of the invasion of Phlox paniculata L. and Ph. setacea L.
      by causative agents of the phlox powdery mildew (compatible combination) and
      lupine powdery mildew (incompatible combination) on the level of endogenous
      cytokinins and abscisic and salicylic acids. In all experimental variants, the
      level of zeatin-riboside and abscisic and salicylic acids in the leaves of
      invaded plants increased within 48 h. The highest level of phytohormones and
      salicylic acid was recorded in the absolutely resistant species Ph. setacea.

PMID- 11525124
TI  - [Antifungal activity of aqueous extracts from the leaf of cowparsnip and
      comfrey].
AB  - We found that extracts from the leaves of medicinal comfrey and cowparsnip
      strongly inhibit the germination of Erysiphe graminis conidia and uredospores of
      Puccinia graminis. Spraying wheat seedlings with these extracts, in contrast to
      the irrigation of soil, markedly diminished infection in plants with powdery
      mildew. Antifungal activity in vitro and protective activity (when plants were
      sprayed) correlated with the level of phenolic compounds in these extracts.
      Experiments with healthy plants have demonstrated that the photosynthetic
      apparatus of wheat plants is stimulated by extracts. Spraying seedlings with the
      extracts resulted in an increased rate of O2 evolution calculated per unit of
      chlorophyll, an increase in the ratio (FM-FT)/FT in the experiments that recorded
      slow fluorescence induction, an increase in the relative light intensity of band
      A, and a decrease of relative intensity of band C in experiments with
      thermoluminescence of wheat leaves. These results provide evidence that the
      protective activity of comfrey and cowparsnip extracts is associated with their
      action on the pathogenic fungus and with the activation of natural defense
      reactions of the host plant.

PMID- 11525125
TI  - [Structural characteristics of certain Rodents spines (Rodentia: Myomorpha,
      Hystricomorpha)].
AB  - The architectonics of spines and hair was studied in Neacomys spinosus,
      Arvicanthis somalicus, Leopoldamys sabanus, L. edwardsi, Maxomys moi, M. surifer,
      Niviventer fulvescens, N. confucianus, N. cremoriventer, Acomys cahirinus, A.
      somalica, Hystrix indica, H. cristata, Atherurus macrourus, Erethizon dorsatum,
      Proechimys steerei, and Lonchotrix emiliae. The presence of a dorsal longitudinal
      furrow covered by a modified cuticle is a common structural feature of spines in
      all studied species except E. dorsatum, H. indica, and the frontal surface of the
      mosaic (scales located side by side) and terrace cuticle (steps between scales)
      varies in different species from smooth to rib-folded. A terminology has been
      proposed to describe the main structures of spine and hair. The adaptive
      significance of the spine architectonics in rodents is discussed.

PMID- 11525126
TI  - [Mechanisms of suppression of alcohol motivation after immunization of albino
      rats against alcohol dehydrogenase I: The role of ADH epitopes and ADH activity
      in the adrenal glands].
AB  - Experimental results have demonstrated a significant decrease in the level of
      alcohol consumption by albino rats immunized with heterologous horse alcohol
      dehydrogenase. The role of ADH epitopes 9-14, 93-115, and 265-276 in this
      phenomenon was examined, and it was established that the latter sequence (265
      276) plays the biggest role. The inhibition of ADH activity in the adrenals of
      immunized rats was much higher compared to the liver. We propose a hypothesis
      that the effect of alcohol dehydrogenase on alcohol consumption is connected with
      its role in catecholamine metabolism.

PMID- 11525127
TI  - [Anti-stress effect of nitric oxide].
AB  - Rat strains feature different resistances to stress. The increased production of
      nitric oxide (NO) in the August strain prevents the appearance of ulcerous
      lesions of gastric mucosa and behavioral changes induced by restraint stress.
      Wistar rats feature a lower level of NO production and are more sensitive to
      restraint stress compared to the August rats according to both the ulcer
      pathology and behavioral indices. The stress-induced release of catecholamines
      was reproduced by experimental hyperfunction of the dopaminergic (DA) system
      induced by the introduction of L-DOPA. Introduction of NO synthase inhibitor N
      omega-nitro-L-arginine (L-NNA) enhanced the L-DOPA-induced behavioral changes.
      This effect was more pronounced in the August strain. The introduction of the
      exogenous NO donor, dinitrosyl iron complexes (DNIC), limited the behavioral
      disturbances induced by L-DOPA in both rat strains. The protective effect of DNIC
      in conditions of the DA system hyperfunction is similar to the effect of a D2
      blocker sulpiride. Thus, NO has a central antistress effect, apparently, mediated
      by limiting the release of catecholamines.

PMID- 11525128
TI  - [Hypnogenic properties of DSIP peptide analogs: structural-functional
      relationship].
AB  - The sleep-inducing activity of Delta Sleep-Inducing Peptide (DSIP) and its 13
      synthetic analogs has been studied on rabbits with preliminary implanted
      electrodes. The peptides were injected into the lateral ventricle of cerebrum.
      Polygraphic computer monitoring of sleep-wake states was carried out at daytime
      for 7-12 h. DSIP and most analogs had no statistically significant effect on
      sleep compared to the control administration of saline to the same animals.
      [NMeAla2]DSIP and [Pro2]DSIP had a pronounced sleep-inducing effect and reliably
      increased the proportion of slow-wave sleep by 10-15% on average compared to the
      control. Several other analogs had a week sleep-inducing effect, increasing the
      proportion of slow-wave sleep during specific recording time only. [beta
      Ala2]DSIP significantly suppressed sleep. In addition, this analog, as well as
      parent DSIP and four proline-containing nonapeptides, slightly increased the body
      temperature. The revealed differences may be due to both conformation properties
      and proteolytic resistance of the studied molecules, and it may reflect their
      indirect involvement in the control sleep-wake hormonal processes.

PMID- 11525129
TI  - [Finding of the tropical group testate amoebae (Protozoa: Testacea) at the Far
      East ( Sikhote Alin Reserve)].
AB  - Testate amoebae species Hoogenraadia humicola, Planhoogenraadia media, and
      Distomatopyxis couillardi of the Gondwana-tropical and tropical groups have been
      found for the first time in the territory of Russia. Brown and dark-colored soil
      of oak forest in Primorsky Kray (Sikhote Alin Reserve, northeast part of the East
      Asian Holarctic) are the northernmost range of these tropical species. The
      morphometric data are presented and the specific composition of the communities
      and geographical distribution of the tropical group species are discussed. A new
      species Planhoogenraadia daurica Bobrov has been described.

PMID- 11525130
TI  - [Typology of landscape-regional distribution of the Acridoidea species in grass
      biotopes of south-west Siberia based on isopleth portraits of their quantitative
      distribution].
AB  - The ranges of Orthoptera species are analyzed with reference to their
      geographical distribution and quantitative distribution in elementary landscapes.
      A common system has been plotted for 131 species and subspecies based on the data
      of three continental transects with up to 30 vertical-layer landscapes in each.

PMID- 11525131
TI  - [Characteristics of species and structural diversity of artificial pine stands on
      soddy-podzolic loam soils].
AB  - The method of ecological transects was used for studying plant-species
      composition in an aged artificial pine stand created on a composite spruce forest
      on soddy-podzolic soil (underlain by blanket loams) in the broad-leaved-spruce
      forest subzone (Moscow oblast). The change of edificatory tree species was
      followed by changes in the ecological conditions and, as a consequence, in the
      species composition, abundance, and cenotic significance of vegetation. Changes
      in the pattern of restoration of floristic diversity in different soil
      geochemical facies of the transect were observed.

PMID- 11525132
TI  - [Hormonal balance of wheat infected with Helminthosporium sativum].
AB  - Using immunoenzyme assay, we studied the levels of phytohormones in resistant and
      susceptible varieties of wheat infected with Helminthosporium sativum. The
      infection of wheat with this pathogen leads to an increase in cytokinins in
      plants of the resistant variety in the presence of stable IAA/ABA ratio. The
      level of ABA increases in the infected plants of the susceptible variety. The
      role of hormones in the mechanisms of plant resistance to fungal infections is
      discussed.

PMID- 11525133
TI  - [The role of beta-adrenoreceptors in pathogenesis of neurogenic dystrophies].
AB  - Sciatic nerve damage led to a defective functioning of the renal
      mineralocorticoid receptors due to the disturbed neurotrophic supply of this
      organ: the reception of distorted nervous stimuli. The pharmacological blockade
      of both the neurotransmitter and the humoral pathways of the pathological stimuli
      from the damaged nerve to the kidney prevented the development of trophic
      disturbances as tested by the state of the renal mineralocorticoid receptor
      system. At the same time, the pharmacological stimulation of the sympathetic
      nervous system leads to an even more defective aldosterone reception by the
      kidney. Propranolol exerted an antidystrophic effect in the case of local damages
      of the nervous system and, thereby, prevented the development of neurogenic
      dystrophies.

PMID- 11525134
TI  - [Ecologo-economical model of the region development based on the expert approach
      (example of Bieszczad montain region, Poland)].
AB  - A computer simulation has been developed for the dynamics of forest communities
      and abundance of wild animals in the Bieszczad mountain region (Carpathians,
      Southern Poland) at the background of changing quality of water resulting from
      the development of tourism and agriculture. The simulation operates on scaled
      variables in the 0-1 range. The functional relationships in the simulation were
      determined by the Delphi evaluation. The simulation was used to consider
      scenarios of various environmental influences of the region-climatic factors
      (warming and changed rainfall) as well as anthropogenic disturbances (development
      of tourism, agriculture, and commercial hunting). The simulation can be adapted
      for other regions.

PMID- 11525135
TI  - Time does not heal all wounds. Patients report lower satisfaction levels as time
      goes by.
AB  - Tracking patient satisfaction over time is an effective way to learn about
      patient perceptions and can also help draw attention to service areas that need
      improvement. This research compared patient satisfaction levels immediately
      following hospital discharge and then again two years later. Both overall
      satisfaction and satisfaction with particular attributes tended to decrease over
      time. These findings raise questions about the long-term stability of
      satisfaction ratings and have implications for the timing of satisfaction
      surveys.

PMID- 11525136
TI  - Forecasting the health care future. Futurescan 2001 and its implications for
      health care marketing.
AB  - In his new book, futurist Russell C. Coile Jr. presents predictions about seven
      aspects of health care for the next five years. Aided by a panel of health care
      experts, he analyzes likely developments in health care consumerism, technology,
      managed care, and other areas that raise a number of issues for health care
      marketers. Even if only a few of these predictions come true, marketers will be
      forced to rethink some of their techniques to adapt to this rapidly changing
      environment.

PMID- 11525137
TI  - Will database marketing work in health care? The experts debate whether it exists
      and if health care can benefit from it.

PMID- 11525138
TI  - The changing face of pharmaceutical advertising. A look at medical journals
      reveals a new era in advertising.

PMID- 11525139
TI  - A healthy start. Offering newcomers healthy advice when they arrive can create
      customers for life.

PMID- 11525140
TI  - Getting to know the women's health care segment. Meeting women's needs means
      raising the marketing bar.

PMID- 11525142
TI  - Reading the literature.

PMID- 11525141
TI  - Has the Web really empowered health care consumers? The truth is customers may
      not have changed as much as we think.
AB  - The experts tell us that fueled by unprecedented access to health information
      online, today's new health care consumer will revolutionize the way health care
      services are organized and delivered. An examination of consumers from a health
      value-graphic perspective, however, casts some doubt on these predictions.
      Patterns emerging online are simply making us more aware of existing consumer
      segments that have always been actively involved in their own health.

PMID- 11525143
TI  - Continuing medical education. An effective tool or a faulty fantasy?

PMID- 11525144
TI  - Wouldn't it be nice.

PMID- 11525145
TI  - Reading clinical research. A flaw catching exercise.

PMID- 11525146
TI  - Pharmaceutical companies and our education.

PMID- 11525147
TI  - Office EMR.

PMID- 11525148
TI  - The Maryland Cigarette Restitution Fund. Fighting cancer and tobacco use on the
      public health front.

PMID- 11525150
TI  - The M.D., the V.P., and the I.C.D.

PMID- 11525151
TI  - Continuing medical education.

PMID- 11525152
TI  - Deltamethrin tolerance & associated cross resistance in Aedes aegypti from
      Mysore.
AB  - BACKGROUND & OBJECTIVES: The indiscriminate use of insecticides in public health
      and agriculture has led to the development of resistance to these insecticides in
      the vector mosquitoes. To understand the development of resistance to synthetic
      pyrethroids, selection studies on Aedes aegypti were done at Mysore. METHODS: Ae.
      aegypti collected from the field were subjected to selection experiment with
      deltamethrin for 16 generations in the laboratory. Cross resistance test was
      conducted against permethrin and fenvalerate. RESULTS: Tolerance level was found
      to increase by 333.83 folds in terms of its LC50 values. Cross resistance of this
      deltamethrin selected line was tested against permethrin and fenvalerate. The
      results show that the selected line has developed cross resistance as much as
      5.19 and 5.92 folds respectively against permethrin and fenvalerate.
      INTERPRETATION & CONCLUSIONS: The findings show a continuous elevation in
      tolerance in Ae. aegypti with increase in deltamethrin selection pressure, and
      development of cross resistance to other insecticides of the same class. The
      natural or developed tolerance has its implications in the control of these
      mosquitoes.

PMID- 11525153
TI  - Laboratory & field evaluation of controlled release formulation of the insect
      repellents N,N-diethyl-m-toluamide (DEET) & N,N-diethyl phenylacetamide (DEPA)
      against mosquito vectors.
AB  - BACKGROUND & OBJECTIVES: Repellents can play a useful role in reducing the man
      vector contact and help in interrupting disease transmission. Newer formulations
      are necessary to improve the efficacy of the repellent on the treated sites for
      enhanced protection. METHODS: To determine the comparative efficacy, 20 per cent
      liposphere lotion formulation and 20 per cent alcohol solution of two insect
      repellents DEET and DEPA were evaluated for the extent of protection on rabbits
      against Aedes aegypti during the day in the laboratory and on human volunteers
      during the night against Culex quinquefasciatus in the urban areas of
      Pondicherry, India. RESULTS: In the laboratory, the lotion formulations of DEPA
      and DEET were found to enhance the repellency by 1.5 (4.00 to 6.00 h) and 1.25
      (4.00 to 5.00 h) times respectively compared to the alcohol solution of the
      repellents against Ae. aegypti at the application rate of 0.5 mg/cm2. In the
      field, the lotion formulation of DEPA at 0.3 mg/cm2 could increase the protection
      time from 6.30 to 8.36 h (1.3 times) whereas the lotion formulation of DEET at
      0.3 mg/cm2 could increase the protection time from 6.54 to 8.42 h (1.2 times).
      INTERPRETATION & CONCLUSION: In laboratory and field tests, the lotion
      formulations of both repellents were found to give a higher protection compared
      to alcohol solution. The lotion formulations of DEET and DEPA were found to be
      equally effective.

PMID- 11525154
TI  - Suppression of beta 2 microglobulin by pentoxiphylline therapy in asymptomatic
      HIV infected individuals.
AB  - Pentoxiphylline, an inhibitor of tumor necrosis factor-alpha (TNF-alpha) has been
      used in the treatment of human immunodeficiency virus (HIV) infection. The
      inhibition of TNF-alpha results in decreased immune activation. Beta 2
      microglobulin (beta 2 M) has been used as a surrogate marker to study the
      progression of HIV infection. The objective of this study was to see if use of
      pentoxiphylline resulted in any decline in beta 2 M levels. Twenty patients with
      HIV infection who were free of opportunistic infections at the time of inclusion
      in the study and 18 age and sex matched controls were studied. beta 2 M was
      measured using an enzyme immunoassay before and four weeks after the start of
      treatment with pentoxiphylline. Mean levels of beta 2 M before therapy were 1.51
      +/- 0.77 mg/l (range 0.78-3.8 mg/l) and were significantly higher (P < 0.001)
      than the levels among controls [0.72 +/- 0.06 mg/l (range 0.46-0.88 mg/l)]. beta
      2 M levels in patients declined to 0.85 +/- 0.22 mg/l (range 0.72-1.0 mg/l) after
      four weeks of therapy and this was statistically significant (P < 0.001). Use of
      pentoxiphylline for four weeks results in a significant decline in the levels of
      beta 2 M suggesting that the level of immune activation is reduced with the
      therapy.

PMID- 11525155
TI  - Comparative analysis of monoclonal antibody based enzyme immunoassay, modified
      genome electrophoresis & electron microscopy procedures for rotavirus diagnosis
      from faecal specimens.
AB  - BACKGROUND & OBJECTIVES: Reliable and rapid diagnosis of rotavirus infection is
      necessary for patient management. Several newly introduced commercial enzyme
      immunoassays (ELISAs) have been evaluated using direct electron microscopy (DEM)
      with or without direct ultracentrifugation as the standard reference method, and
      have shown varying results. METHODS: In the present study we compared the
      diagnostic efficacy of the three methods viz., monoclonal antibody (MAb) ELISA,
      modified polyacrylamide gel electrophoresis (PAGE) and DEM without
      ultracentrifugation in the detection of rotaviruses from 211 stool specimens. The
      data were analysed by two latent class model (2LC) in the absence of a gold
      standard reference method. RESULTS: Rotavirus was detected in 42 specimens by MAb
      ELISA; in 40 specimens by PAGE and in 33 specimens by DEM. The estimates of
      sensitivities and specificities of the three methods were analysed by 2LC method.
      The analysis revealed no significant variation among the three methods. However,
      DEM was found with a comparatively lesser sensitivity over the other two methods.
      INTERPRETATION & CONCLUSIONS: Though DEM was found to be relatively less
      sensitive than the other two methods, the differences were not significant, and
      all the three methods were highly specific. Moreover, DEM has the additional
      advantage of detecting non-group A and other gastroenteritis viruses. The
      findings suggest the use of highly sensitive and specific MAb-ELISA and PAGE in
      parallel to detect group A, non-group A and atypical rotavirus infection in the
      population.

PMID- 11525156
TI  - Mycobacterium fortuitum wound infection following laparoscopy.
AB  - During a six week period in 1999, seven patients who underwent laparoscopic
      tubectomies at small town health centres near Chandigarh developed chronic
      discharging sinuses at the site of incision. Mycobacterium fortuitum was isolated
      from wound discharge of the five patients by standard methods and two patients
      were smear positive. Environmental samples e.g., tap water, and a variety of
      fluids did not yield any mycobacteria and swabs from different parts of the
      laparoscope were sterile. All patients responded to ciprofloxacin and amikacin
      therapy. Our observation demonstrates that M. fortuitum is a clinically important
      nosocomial pathogen in setting of surgical wound infection in our country.

PMID- 11525157
TI  - Typing of Aeromonas isolates from children with diarrhoea & water samples by
      randomly amplified polymorphic DNA polymerase chain reaction & whole cell protein
      fingerprinting.
AB  - BACKGROUND & OBJECTIVES: Aeromonas spp. are water-borne organisms, often
      associated with childhood diarrhoea. The present study was conducted to examine
      the epidemiological relationship among the Aeromonas spp. isolated from water and
      children with acute diarrhoea in Chennai. METHODS: Thirty six Aeromonas isolates
      inclusive of 16 from children with diarrhoea, 15 from domestic water samples and
      5 reference strains were studied by randomly amplified polymorphic DNA polymerase
      chain reaction (RAPD-PCR). Twenty eight Aeromonas isolates, 15 from children with
      diarrhoea, 10 from domestic water samples and three reference strains were
      analysed by SDS-PAGE for their whole cell protein profiles. RESULTS: The 36
      Aeromonas isolates examined by RAPD-PCR generated RAPD fingerprints with majority
      of the bands ranging from about 250 to 2800 bp. The RAPD fingerprints did not
      correspond with the phenospecies and varied greatly among the strains within the
      phenospecies. Cluster analysis revealed two major groups at 75 per cent
      hierarchical level, comprising 18 Aeromonas isolates, mainly recovered from
      domestic water samples, while the clinical isolates were scattered in different
      hierarchical levels in the dendrogram. The whole cell protein fingerprints
      examined by SDS-PAGE did not correspond with the phenospecies. Only four isolates
      of A. caviae were found to produce similar protein fingerprints allowing them to
      form a cluster at about 90 per cent hierarchical level, while the rest of the
      isolates were scattered at various hierarchical levels in the dendrogram.
      INTERPRETATION & CONCLUSIONS: In the present study, RAPD fingerprinting was found
      to be useful in distinguishing Aeromonas isolates recovered from clinical and
      domestic water supplies. However, RAPD-PCR could not distinguish the phenospecies
      of the genus Aeromonas. Whole cell protein fingerprinting and cluster analysis
      could neither differentiate isolates from clinical and domestic water sources nor
      the phenospecies of the genus Aeromonas.

PMID- 11525159
TI  - [XX Congress of the Spanish Society of Family and Community Medicine. 8-11
      November 2000, Asturias. Abstracts].

PMID- 11525158
TI  - Laboratory evaluation of repellents against Leptotrombidium deliense, vector of
      scrub typhus.
AB  - BACKGROUND & OBJECTIVES: Scrub typhus, a rickettsial disease transmitted by
      larvae of Leptotrombidium deliense, is of special importance to the Armed Forces
      personnel, due to the heightened risk to this disease during movement in mite
      endemic areas during exercise/war. The disease is best prevented by the use of
      personal protective measures including repellents. Studies were undertaken to
      determine the relative efficacy of repellents: diethyl toulamide (DEET), dibutyl
      phthalate (DBP) with an indigenously developed repellent diethyl phenyl acetamide
      (DEPA) against the larval trombiculid mite. METHODS: The repellents were tested
      for persistence on impregnated cloth prior to washing, post washing and ironing
      by means of a specially fabricated testing kit. Acaricidal efficacy estimation
      was performed on the treated fabrics and topical application efficacy of
      repellents on mice was evaluated by a novel animal testing model. RESULTS: DEET
      and DEPA were found to provide maximum protection (repellence and acaricidal
      efficacy), could withstand two launderings of the impregnated uniform and also
      had superior efficacy on topical application (8 h). Ironing was found to
      significantly reduce the repellence of DEET and DBP. INTERPRETATION & CONCLUSION:
      The findings of this study point towards the superiority of DEPA and DEET for
      impregnation of the uniform cloth as well as for topical application for the
      prevention of scrub typhus amongst the troops.

PMID- 11525160
TI  - 32nd Annual meeting of the Swiss Society of Nephrology. Lausanne, 14-15 December
      2000. Abstracts.

PMID- 11525161
TI  - [German Society of Analytical Chemistry specialty group communications. April
      2000].

PMID- 11525162
TI  - Pneumatization of the pterygoid process of the sphenoid bone.

PMID- 11525163
TI  - [Inflammatory pseudotumor of abdominal cavity, simulating tumor of cecum].

PMID- 11525164
TI  - Structure of apoptosis-linked protein ALG-2: insights into Ca2+-induced changes
      in penta-EF-hand proteins.
AB  - BACKGROUND: The Ca2+ binding apoptosis-linked gene-2 (ALG-2) protein acts as a
      proapoptotic factor in a variety of cell lines and is required either downstream
      or independently of caspases for apoptosis to occur. ALG-2 belongs to the penta
      EF-hand (PEF) protein family and has two high-affinity and one low-affinity Ca2+
      binding sites. Like other PEF proteins, its N terminus contains a Gly/Pro-rich
      segment. Ca2+ binding is required for the interaction with the target protein,
      ALG-2 interacting protein 1 (AIP1). RESULTS: We present the 2.3 A resolution
      crystal structure of Ca2+-Ioaded des1-20ALG-2 (aa 21-191), which was obtained by
      limited proteolysis of recombinant ALG-2 with elastase. The molecule contains
      eight alpha helices that fold into five EF-hands, and, similar to other members
      of this protein family, the molecule forms dimers. Ca2+ ions bind to EF1, EF3,
      and, surprisingly, to EF5. In the related proteins calpain and grancalcin, the
      EF5 does not bind Ca2+ and is thought to primarily facilitate dimerization. Most
      importantly, the conformation of des1-20ALG-2 is significantly different from
      that of calpain and grancalcin. This difference can be described as a rigid body
      rotation of EF1-2 relative to EF4-5 and the dimer interface, with a hinge within
      the EF3 loop. An electron density, which is interpreted as a hydrophobic Gly/Pro
      rich decapeptide that is possibly derived from the cleaved N terminus, was found
      in a hydrophobic cleft between these two halves of the molecule. CONCLUSIONS: A
      different relative orientation of the N- and C-terminal halves of des1-20ALG-2 in
      the presence of Ca2+ and the peptide as compared to other Ca2+loaded PEF proteins
      changes substantially the shape of the molecule, exposing a hydrophobic patch on
      the surface for peptide binding and a large cleft near the dimer interface. We
      postulate that the binding of a Gly/ Pro-rich peptide in the presence of Ca2+
      induces a conformational rearrangement in ALG-2, and that this mechanism is
      common to other PEF proteins.

PMID- 11525165
TI  - Solution structure of B. subtilis acyl carrier protein.
AB  - BACKGROUND: Acyl carrier protein (ACP) is a fundamental component of fatty acid
      biosynthesis in which the fatty acid chain is elongated by the fatty acid
      synthetase system while attached to the 4'-phosphopantetheine prosthetic group
      (4'-PP) of ACP. Activation of ACP is mediated by holo-acyl carrier protein
      synthase (ACPS) when ACPS transfers the 4'-PP moiety from coenzyme A (CoA) to
      Ser36 of apo-ACP. Both ACP and ACPS have been identified as essential for E. coli
      viability and potential targets for development of antibiotics. RESULTS: The
      solution structure of B. subtilis ACP (9 kDa) has been determined using two
      dimensional and three-dimensional heteronuclear NMR spectroscopy. A total of 22
      structures were calculated by means of hybrid distance geometry-simulated
      annealing using a total of 1,050 experimental NMR restraints. The atomic rmsd
      about the mean coordinate positions for the 22 structures is 0.45 +/- 0.08 A for
      the backbone atoms and 0.93 +/- 0.07 A for all atoms. The overall ACP structure
      consists of a four alpha-helical bundle in which 4'-PP is attached to the
      conserved Ser36 that is located in alpha helix II. CONCLUSIONS: Structural data
      were collected for both the apo and holo forms of ACP that suggest that the two
      forms of ACP are essentially identical. Comparison of the published structures
      for E. coli ACP and actinorhodin polyketide synthase acyl carrier protein (act
      apo-ACP) from Streptomyces coelicolor A3(2) with B. subtilis ACP indicates
      similar secondary structure elements but an extremely large rmsd between the
      three ACP structures (>4.3 A). The structural difference between B. subtilis ACP
      and both E. coli and act apo-ACP is not attributed to an inherent difference in
      the proteins, but is probably a result of a limitation in the methodology
      available for the analysis for E. coli and act apo-ACP. Comparison of the
      structure of free ACP with the bound form of ACP in the ACP-ACPS complex reveals
      a displacement of helix II in the vicinity of Ser36. The induced perturbation of
      ACP by ACPS positions Ser36 proximal to coenzyme A and aligns the dipole of helix
      II to initiate transfer of 4'-PP to ACP.

PMID- 11525166
TI  - Crystal structure of Streptococcus mutans pyrophosphatase: a new fold for an old
      mechanism.
AB  - BACKGROUND: Streptococcus mutans pyrophosphatase (Sm-PPase) is a member of a
      relatively uncommon but widely dispersed sequence family (family II) of inorganic
      pyrophosphatases. A structure will answer two main questions: is it structurally
      similar to the family I PPases, and is the mechanism similar? RESULTS: The first
      family II PPase structure, that of homodimeric Sm-PPase complexed with metal and
      sulfate ions, has been solved by X-ray crystallography at 2.2 A resolution. The
      tertiary fold of Sm-PPase consists of a 189 residue alpha/beta N-terminal domain
      and a 114 residue mixed beta sheet C-terminal domain and bears no resemblance to
      family I PPase, even though the arrangement of active site ligands and the
      residues that bind them shows significant similarity. The preference for Mn2+
      over Mg2+ in family II PPases is explained by the histidine ligands and bidentate
      carboxylate coordination. The active site is located at the domain interface. The
      C-terminal domain is hinged to the N-terminal domain and exists in both closed
      and open conformations. CONCLUSIONS: The active site similiarities, including a
      water coordinated to two metal ions, suggest that the family II PPase mechanism
      is "analogous" (not "homologous") to that of family I PPases. This is a
      remarkable example of convergent evolution. The large change in C-terminal
      conformation suggests that domain closure might be the mechanism by which Sm
      PPase achieves specificity for pyrophosphate over other polyphosphates.

PMID- 11525167
TI  - The crystal structure of Escherichia coli MoeA and its relationship to the
      multifunctional protein gephyrin.
AB  - BACKGROUND: Molybdenum cofactor (Moco) biosynthesis is an evolutionarily
      conserved pathway present in archaea, eubacteria, and eukaryotes. In humans,
      genetic abnormalities in the biosynthetic pathway result in Moco deficiency,
      which is accompanied by severe neurological symptoms and death shortly after
      birth. The Escherichia coli MoeA and MogA proteins are involved in the final step
      of Moco biosynthesis: the incorporation of molybdenum into molybdopterin (MPT),
      the organic pyranopterin moiety of Moco. RESULTS: The crystal structure of E.
      coli MoeA has been refined at 2 A resolution and reveals that the highly
      elongated MoeA monomer consists of four clearly separated domains, one of which
      is structurally related to MogA, indicating a divergent evolutionary relationship
      between both proteins. The active form of MoeA is a dimer, and a putative active
      site appears to be localized to a cleft formed between domain II of the first
      monomer and domains III and IV of the second monomer. CONCLUSIONS: In eukaryotes,
      MogA and MoeA are fused into a single polypeptide chain. The corresponding
      mammalian protein gephyrin has also been implicated in the anchoring of
      glycinergic receptors to the cytoskeleton at inhibitory synapses. Based on the
      structures of MoeA and MogA, gephyrin is surmised to be a highly organized
      molecule containing at least five domains. This multidomain arrangement could
      provide a structural basis for its functional diversity. The oligomeric states of
      MoeA and MogA suggest how gephyrin could assemble into a hexagonal scaffold at
      inhibitory synapses.

PMID- 11525168
TI  - Crystal structures of a novel ferric reductase from the hyperthermophilic
      archaeon Archaeoglobus fulgidus and its complex with NADP+.
AB  - BACKGROUND: Studies performed within the last decade have indicated that
      microbial reduction of Fe(III) to Fe(II) is a biologically significant process.
      The ferric reductase (FeR) from Archaeoglobus fulgidus is the first reported
      archaeal ferric reductase and it catalyzes the flavin-mediated reduction of
      ferric iron complexes using NAD(P)H as the electron donor. Based on its catalytic
      activity, the A. fulgidus FeR resembles the bacterial and eukaryotic assimilatory
      type of ferric reductases. However, the high cellular abundance of the A.
      fulgidus FeR (approximately 0.75% of the total soluble protein) suggests a
      catabolic role for this enzyme as the terminal electron acceptor in a ferric iron
      based respiratory pathway [1]. RESULTS: The crystal structure of recombinant A.
      fulgidus FeR containing a bound FMN has been solved at 1.5 A resolution by
      multiple isomorphous replacement/ anomalous diffraction (MIRAS) phasing methods,
      and the NADP+- bound complex of FeR was subsequently determined at 1.65 A
      resolution. FeR consists of a dimer of two identical subunits, although only one
      subunit has been observed to bind the redox cofactors. Each subunit is organized
      around a six-stranded antiparallel beta barrel that is homologous to the FMN
      binding protein from Desulfovibrio vulgaris. This fold has been shown to be
      related to a circularly permuted version of the flavin binding domain of the
      ferredoxin reductase superfamily. The A. fulgidus ferric reductase is further
      distinguished from the ferredoxin reductase superfamily by the absence of a
      Rossmann fold domain that is used to bind the NAD(P)H. Instead, FeR uses its
      single domain to provide both the flavin and the NAD(P)H binding sites. Potential
      binding sites for ferric iron complexes are identified near the cofactor binding
      sites. CONCLUSIONS: The work described here details the structures of the enzyme
      FMN, enzyme-FMN-NADP+, and possibly the enzyme-FMN-iron intermediates that are
      present during the reaction mechanism. This structural information helps identify
      roles for specific residues during the reduction of ferric iron complexes by the
      A. fulgidus FeR.

PMID- 11525169
TI  - Structure of CD40 ligand in complex with the Fab fragment of a neutralizing
      humanized antibody.
AB  - BACKGROUND: CD40 ligand (CD40L or CD154), a member of the tumor necrosis factor
      (TNF) family, plays a critical role in both humoral and cellular immune responses
      and has been implicated in biological pathways involving epithelial cells,
      fibroblasts, and platelets. Such a pathway is T cell-mediated B cell activation,
      a process that occurs through the interaction of CD40L with CD40 receptor
      expressed on B cells. It results in various B cell responses, including
      immunoglobulin isotype switching and B cell differentiation and proliferation.
      These responses can be inhibited by the monoclonal antibody 5c8, which binds with
      high affinity to CD40L. RESULTS: To understand the structural basis of the
      inhibition, we determined the crystal structure of the complex of the
      extracellular domain of CD40L and the Fab fragment of humanized 5c8 antibody. The
      structure shows that the complex has the shape of a three-bladed propeller with
      three Fab fragments bound symmetrically to a CD40L homotrimer. To further study
      the nature of the antibody-antigen interface, we assessed the ability of 23 site
      directed mutants of CD40L to bind to 5c8 and CD40 and analyzed the results in the
      context of the crystal structure. Finally, we observed via confocal microscopy
      that 5c8 binding to CD40L on the cell surface results in the formation of patches
      of clustered complexes. CONCLUSIONS: The structure reveals that 5c8 neutralizes
      CD40L function by sterically blocking CD40 binding. The antigenic epitope is
      localized in a region of the surface that is likely to be structurally perturbed
      as a result of genetic mutations that cause hyper-IgM syndrome. The symmetric
      trimeric arrangement of the Fab fragments in the complex results in a geometry
      that facilitates the formation of large clusters of complexes on the cell
      surface.

PMID- 11525170
TI  - Structural evidence for a possible role of reversible disulphide bridge formation
      in the elasticity of the muscle protein titin.
AB  - BACKGROUND: The giant muscle protein titin contributes to the filament system in
      skeletal and cardiac muscle cells by connecting the Z disk and the central M line
      of the sarcomere. One of the physiological functions of titin is to act as a
      passive spring in the sarcomere, which is achieved by the elastic properties of
      its central I band region. Titin contains about 300 domains of which more than
      half are folded as immunoglobulin-like (Ig) domains. Ig domain segments of the I
      band of titin have been extensively used as templates to investigate the
      molecular basis of protein elasticity. RESULTS: The structure of the Ig domain I1
      from the I band of titin has been determined to 2.1 A resolution. It reveals a
      novel, reversible disulphide bridge, which is neither required for correct
      folding nor changes the chemical stability of I1, but it is predicted to
      contribute mechanically to the elastic properties of titin in active sarcomeres.
      From the 92 Ig domains in the longest isoform of titin, at least 40 domains have
      a potential for disulphide bridge formation. CONCLUSIONS: We propose a model
      where the formation of disulphide bridges under oxidative stress conditions could
      regulate the elasticity of the I band in titin by increasing sarcomeric
      resistance. In this model, the formation of the disulphide bridge could refrain a
      possible directed motion of the two beta sheets or other mechanically stable
      entities of the I1 Ig domain with respect to each other when exposed to
      mechanical forces.

PMID- 11525171
TI  - Crystal structure of the soluble form of equinatoxin II, a pore-forming toxin
      from the sea anemone Actinia equina.
AB  - BACKGROUND: Membrane pore-forming toxins have a remarkable property: they adopt a
      stable soluble form structure, which, when in contact with a membrane, undergoes
      a series of transformations, leading to an active, membrane-bound form. In
      contrast to bacterial toxins, no structure of a pore-forming toxin from an
      eukaryotic organism has been determined so far, an indication that structural
      studies of equinatoxin II (EqtII) may unravel a novel mechanism. RESULTS: The
      crystal structure of the soluble form of EqtII from the sea anemone Actinia
      equina has been determined at 1.9 A resolution. EqtII is shown to be a single
      domain protein based on a 12 strand beta sandwich fold with a hydrophobic core
      and a pair of alpha helices, each of which is associated with the face of a beta
      sheet. CONCLUSIONS: The structure of the 30 N-terminal residues is the largest
      segment that can adopt a different structure without disrupting the fold of the
      beta sandwich core. This segment includes a three-turn alpha helix that lies on
      the surface of a beta sheet and ends in a stretch of three positively charged
      residues, Lys-30, Arg-31, and Lys-32. On the basis of gathered data, it is
      suggested that this segment forms the membrane pore, whereas the beta sandwich
      structure remains unaltered and attaches to a membrane as do other structurally
      related extrinsic membrane proteins or their domains. The use of a structural
      data site-directed mutagenesis study should reveal the residues involved in
      membrane pore formation.

PMID- 11525172
TI  - Time-trimming tricks for dynamic simulations: splitting force updates to reduce
      computational work.

PMID- 11525173
TI  - Laboratory monitoring of viral infections and antiviral resistance detection. 13
      June 2000, Istanbul, Turkey. Symposium proceedings.

PMID- 11525174
TI  - Abstracts from the 9th Annual Congress on Women's Health and Gender-Based
      Medicine. June 2-5, 2001, Washington, DC, USA.

PMID- 11525175
TI  - Micronutrients, maternal and child health. Goa, India, 25-27 April 1999.
      Symposium proceedings.

PMID- 11525176
TI  - [Impact of the impaired intestinal microflora on the course of acne vulgaris].
AB  - The paper deals with studies of the intestinal microflora in 114 patients with
      acne vulgaris (94 and 20 with its papulopustular and nodulocystic forms). Sixty
      one (54%) patients have either the first (21%) or second (78.7%) impaired
      bacterial microflora. At the same time, there are no great differences in the
      content of the intestinal microflora in different forms of acne. It is noted that
      adding intestinal microflora-correcting agents to combined therapy in patients
      with papulopustular acne vulgaris and verified dysbacteriosis reduces the
      duration of treatment by over twice and makes its duration the same as that in
      patients without dysbacteriosis.

PMID- 11525177
TI  - [Is Helicobacter pylori a witness or a culprit?].

PMID- 11525178
TI  - [Use of angiotensin-converting enzyme inhibitors in arterial hypertension
      (according to the proceedings of XVI-XXII congresses of European Cardiologic
      Society)].

PMID- 11525179
TI  - [Practice guideline--chronic heart disease].

PMID- 11525180
TI  - Dose and image quality in digital imaging and interventional radiology (DIMOND.
      Proceedings of a workshop. Dublin, Ireland, June 24-26, 1999.

PMID- 11525181
TI  - Bibliography of toxinology.

PMID- 11525182
TI  - [Decision-making in minors].

PMID- 11525183
TI  - [Therapeutic failure with ceftriaxone in a case of exacerbation of chronic
      bronchitis by pneumococcus highly resistant to beta-lactams].

PMID- 11525184
TI  - [Just what is an internist? Introduction to a discussion topic of EFIM (European
      Federation of Internal Medicine)].

PMID- 11525185
TI  - Just what is an internist? An identikit of the specialist in the diseases of
      adults composed of six thumbnail definitions.

PMID- 11525186
TI  - ["Maintaining Life and Health" Symposium, Garmisch-Partenkirchen/Grainau, 2
      December 2000].

PMID- 11525187
TI  - [Do dogs sense when their owner comes?].

PMID- 11525188
TI  - [Arnica for hematomas after venous operations?].

PMID- 11525189
TI  - [Do homeopathic solutions have an internal structure? Studies with NMR
      spectroscopy].

PMID- 11525190
TI  - [Effectiveness of acupuncture in tension headache].

PMID- 11525191
TI  - [Mental healing of chronic pain?].

PMID- 11525192
TI  - [Comparative studies on activities of antimicrobial agents against causative
      organisms isolated from patients with urinary tract infections (1999). III.
      Secular changes in susceptibility].
AB  - The bacteria (Enterococcus faecalis, Staphylococcus aureus, Escherichia coli,
      Klebsiella spp. and Pseudomonas aeruginosa) isolated from patients diagnosed as
      having urinary tract infections (UTIs) in 9 institutions in Japan were supplied
      between the period of August 1999 to July 2000. Then, the susceptibilities of
      these bacteria to various antimicrobial agents were examined and the results were
      compared with those obtained between 1991 and 1998. Comparison was made by
      classifying strains isolated from patients into those with uncomplicated UTIs and
      those with complicated UTIs (including with or without indwelling catheter).
      About E. faecalis, increase of low sensitive strains noted in the former year
      showed a decreasing tendency, however, one strain each with MIC of 4
      micrograms/ml to vancomycin (VCM) was detected in patients with both
      uncomplicated and complicated UTIs. As for S. aureus, many sensitive strains to
      cephems, imipenem (IPM) and VCM were noted, and each MIC50 was better than that
      in the former years. S. aureus strains showing low susceptibility to arbekacin
      (ABK) were detected in patients with complicated UTIs in this year as well as in
      the former year, and one strain each with MIC of 16 micrograms/ml and 32
      micrograms/ml was detected. Susceptibilities of E. coli were effective to all
      drugs except for penicillins and minocycline (MINO). Decrease of low sensitive
      strains was also noted in all drugs except for quinolones. Each MIC90 of
      ciprofloxacin (CPFX) and sparfloxacin (SPFX) in patients with complicated UTIs
      against E. coli was 3 degrees classes lower than that in patients with
      uncomplicated UTIs. As for Klebsiella pneumoniae, decrease of low sensitive
      strains to cephems was noted in patients with uncomplicated UTIs in 1998. In
      1999, low sensitive strains decreased also in patients with complicated UTIs, and
      few were detected. Susceptibilities of K. pneumoniae to quinolones were effective
      as compared with those in the former years with the MIC80s of 0.125 microgram/ml
      or below without detection of low sensitive strains. One low sensitive strain of
      K. pneumoniae with MIC of 8 micrograms/ml was detected for gentamicin (GM).
      Susceptibilities of P. aeruginosa to carbapenems were notable. The MIC90 of
      meropenem (MEPM) and IPM was 4 micrograms/ml each which was 2 degrees better than
      that in 1998. Resistant P. aeruginosa strains to other drugs except for
      monobactams decreased in 1999.

PMID- 11525193
TI  - Swimming through caveolae.

PMID- 11525194
TI  - Choosing family medicine.

PMID- 11525195
TI  - Influence of transmembrane voltage on the structure of membrane components.

PMID- 11525196
TI  - Alphas and taus of tryptophan fluorescence in membranes.

PMID- 11525198
TI  - Can we integrate bioinformatics data on the Internet?
AB  - The NETTAB (Network Tools and Applications in Biology) 2001 Workshop entitled
      'CORBA and XML: towards a bioinformatics-integrated network environment' was held
      at the Advanced Biotechnology Centre, Genoa, Italy, 17-18 May 2001.

PMID- 11525197
TI  - [Radiation-induced cataract: physiopathologic, radiobiologic and clinical
      aspects].
AB  - Cataractogenesis is a widely reported late effect of irradiated crystalline lens.
      In this review the authors discussed the different aspects of radiation cataract
      pathogenesis, and the different mechanisms involved in the lens opacification,
      particularly the epithelium modifications such as epithelial cell death. The
      authors also reported the influence of radiation exposure on cataract formation
      following total body irradiation (TBI) and autologous or allogeneic bone marrow
      transplantation for hematologic malignancies. Moreover, the radiobiological
      parameters are not studied for the crystalline lens of human. We applied for the
      first time the linear-quadratic (LQ) and biological effective dose (BED) concept
      to TBI data. The calculated value of alpha/beta of 1 Gy is in the range of the
      values reported for the other late responding tissues. The other risk factors for
      cataract development after TBI such as age, gender, central nervous system boost,
      long-term steroid therapy and heparin administration are discussed. In terms of
      cataract or sicca syndrome prevention, numerous compounds have been successfully
      tested in experimental models or used for the prevention of radiation-induced
      xerostomia in patients treated for head and neck cancer. However, none of them
      has been clinically evaluated for ocular radiation late effects prevention. In
      this report the authors discussed some of the radioprotectors potentially
      interesting for radiation-induced cataract or sicca syndrome prevention.

PMID- 11525199
TI  - Protein in gels, computers, crystals and camels.
AB  - The IBC's Proteomics 2001 meeting was held in Philadelphia, PA, USA, 14-17 May
      2000.

PMID- 11525200
TI  - Is seed-contamination with GMOs a problem for food safety and the environment?

PMID- 11525202
TI  - [Biology Society membership list, 31 December 2000].

PMID- 11525201
TI  - Diagnosis and management of chronic pericardial effusions.
AB  - Chronic pericardial effusions are a major cause of morbidity in some clinical
      settings. Although the treatment of choice for acute symptomatic pericardial
      effusions (tamponade) is pericardiocentesis, the long-term management of
      symptomatic chronic pericardial effusions provides a greater challenge. The aim
      of this review is to provide insight into the presentation,diagnosis, and
      different treatment options available to patients with chronic symptomatic
      pericardial effusions,with emphasis on malignant pericardial effusions. Peri
      cardiocentesis with sclerosing agents, radiation therapy,percutaneous, and
      surgical pericardiotomy and other surgical techniques are particularly
      efficacious, depend-ing on the underlying cause and the patient's prognosis.

PMID- 11525203
TI  - Clinical grading of peripheral nerve problems.
AB  - To treat peripheral nerve problems appropriately, and to evaluate outcomes of
      peripheral nerve surgery, it is necessary to be able to stage the degree of nerve
      impairment. This article describes quantitative sensory testing that permits the
      necessary measurements for clinical grading of peripheral nerve functions.

PMID- 11525204
TI  - Diagnosis of carpal tunnel syndrome: electrodiagnostic and magnetic resonance
      imaging evaluation.
AB  - In clinically diagnosed CTS without symptoms or signs to suggest other disorders
      that can mimic CTS, it is unclear whether performing nerve conduction studies are
      cost-effective. An outcome study to determine whether nerve conduction studies
      are necessary for the diagnosis may help to clarify this issue. Even less
      evidence exists regarding the cost-effectiveness of imaging for CTS. MR imaging
      reliably depicts normal carpal tunnel anatomic details, including the median and
      ulnar nerves as well as their intraneural fascicular structure. It can also
      identify pathologic nerve compression and mass lesions that compress nerves such
      as ganglion cysts. Currently, MR imaging is probably most commonly used to image
      patients with ambiguous electrodiagnostic studies and clinical examinations. In
      the near future, MR diffusion-weighted imaging should be possible for peripheral
      nerves. As is the case with brain imaging, diffusion-weighted imaging of
      peripheral nerves is likely to be the most sensitive imaging modality for the
      detection of early nerve dysfunction. Electrodiagnostic studies are likely to
      remain the pivotal diagnostic examination in patients with suspected CTS for the
      foreseeable future. With advances in software and hardware, however, high
      resolution MR imaging of peripheral nerves should become faster, less expensive,
      and probably more accurate, possibly paving the way for an expanded role in the
      diagnosis of this common syndrome.

PMID- 11525205
TI  - Endoscopic versus open surgical treatment of carpal tunnel syndrome.
AB  - The impact of CTS is significant as evidenced by the fact that only back injuries
      result in greater rates of employee absenteeism in the workplace. CTR is now the
      most commonly performed surgical procedure in the United States. Earlier efforts
      using open surgical techniques were associated with significant morbidity, which
      some would argue is greater than that associated with the disease itself. The
      addition of endoscopy to surgeon's armamentarium offers the promise of decreased
      morbidity associated with the surgical treatment of CTS. Evidence indicates that
      when compared with open CTR, endoscopic CTR results in earlier achievement of
      patient satisfaction and functional outcomes. As a result, it is becoming clear
      that endoscopic surgery is a safe and effective method of treating CTS.

PMID- 11525206
TI  - Current approach to cubital tunnel syndrome.
AB  - The choice for surgical treatment of cubital tunnel syndrome is no clearer today
      than when it was reviewed 10 years ago. There continue to be no significant
      prospective randomized trials to adequately compare the different surgical
      techniques. Even if such a trial were performed, most hand surgeons would
      probably continue to be skeptical. In the end, each surgeon must rely on his or
      her own personal experience or judgment. Based on the authors' experience in the
      treatment of cubital tunnel syndrome, they are confident that anterior
      transmuscular transposition of the ulnar nerve obtains the best results when the
      preoperative algorithm is properly applied and early postoperative physical
      therapy is instituted.

PMID- 11525207
TI  - Injuries to the brachial plexus: controversies and possibilities.
AB  - The complete supraclavicular traction lesion of the brachial plexus is perhaps
      the most shattering of all injuries of the peripheral nerves. Its highest
      incidence is in young persons, and the results of treatment, although better than
      they were formerly, are still poor.

PMID- 11525208
TI  - Diagnosis and treatment of thoracic outlet syndrome.
AB  - TOS represents a spectrum of disorders encompassing four related syndromes:
      arterial compression, venous compression, neurogenic compression, and a poorly
      defined pain syndrome. Patients can present with signs of arterial insufficiency,
      venous obstruction, painless wasting of intrinsic hand muscles, and pain. History
      and physical examination are the most important diagnostic studies, and
      radiographs of the chest and cervical spine and electromyography/nerve conduction
      studies are useful to identify other causes of pain and disability. Surgical
      intervention is indicated for patients failing nonoperative maneuvers and can
      usually yield satisfactory results. TOS may also be the most underrated,
      overlooked, and misdiagnosed, and the most important and difficult to manage
      peripheral nerve compression in the upper extremity.

PMID- 11525209
TI  - Diagnosis and treatment of piriformis syndrome.
AB  - Piriformis syndrome remains a controversial diagnosis, despite its having first
      been described over 60 years ago. The controversy stems from several factors:
      variable and sometimes unclear cause, similarity to other more easily
      recognizable causes of sciatica, lack of consistent objective diagnostic
      findings, and relative rarity. Nevertheless, it is reasonable to infer that
      sciatic pain may be caused by compression anywhere along its length, from the
      spinal root level to the popliteal fossa, as is peripheral nerve entrapment
      elsewhere in the body. Pathologic changes at the greater sciatic notch may well
      be the source of sciatic pain and should be considered by the clinician. The
      diagnosis of piriformis syndrome remains one of exclusion, however, and in
      patients who present with sciatica, more common causes such as lumbar disease
      should be investigated and ruled out first. After excluding the most common
      causes of sciatica, physicians can use the criteria described here to investigate
      the possibility of piriformis syndrome. If properly diagnosed, it can often be
      treated effectively with either surgical or nonsurgical means.

PMID- 11525210
TI  - Endoscopic upper thoracic sympathectomy.
AB  - Thoracoscopic sympathectomy provides a superb surgical option for the many
      patients with incapacitating essential hyperhidrosis. Whether one thoracoscopic
      approach to sympathectomy is ever likely to prevail is doubtful, as the results
      of the various reported techniques seem to be quite similar. There are definite
      advantages to the single-port approaches, which are faster and usually do not
      require repositioning of the patient to do both sides. In the rare instances
      where dense apical adhesions are encountered or when significant bleeding is
      encountered from one of the intercostal vessels, the two- or three-port
      approaches definitely provide better control (see commentary in article by Kohno
      and Takamoto). Surgeon preference probably dictates which approach is used at the
      different centers. Compensatory sweating remains a frequent and sometimes serious
      complication of the procedure, particularly in individuals living in hot
      climates. An understanding of its mechanisms needs improvement, with the hope of
      preventing its occurrence in the future. In the meantime, patients have to be
      informed of its frequency, and operations could probably be tailored to the
      patients' needs and their local climate.

PMID- 11525211
TI  - Treatment of recurrent peripheral nerve entrapment problems: role of scar
      formation and its possible treatment.
AB  - Surgical management of peripheral nerve entrapment syndromes is usually
      successful, but the recurrence of symptoms after initial improvement can and does
      occur. Extraneural fibrosis is one possible cause of recurrent peripheral nerve
      problems as a result of nerve compression or tethering. Several approaches to
      prevent extraneural scarring after surgery have been studied, including wrapping
      the involved nerve with a graft, the application of various chemical compounds,
      and radiation. ADCON-T/N, an antiscar bioabsorbable gel device was evaluated in a
      retrospective clinical review. Sixty-seven percent of patients treated with ADCON
      T/N after reoperation of a peripheral nerve experienced prolonged clinical
      improvement compared with 50% of patients who did not receive ADCON-T/N. These
      preliminary results suggest that ADCON-T/N may prove to be clinically useful in
      the surgical treatment of peripheral nerve problems. Additional more rigorous
      clinical studies are necessary, however.

PMID- 11525212
TI  - Use of tubes in peripheral nerve repair.
AB  - The use of tubes as an alternative to primary nerve suture in fresh nerve
      transections has been introduced as a biologic approach to nerve injuries,
      creating optimal conditions for axonal regeneration over a short empty space
      intentionally created between the proximal and distal nerve ends. The idea may
      seem controversial and has been criticized using the arguments that silicone in
      itself may create problems like inflammation and the tube may compress the nerve
      ends. With the use of appropriately sized tubes for bridging a maximum 5-mm gap
      in human median and ulnar nerves, the authors have found the technique to be
      useful and persistent at follow-up examinations for up to 4 to 5 years. In
      addition, from the intellectual point of view, the principle illustrates the
      concept by which emphasis is placed on the intrinsic healing capacities of the
      nerve rather than on the technical skill of the surgeon. The thin mesothelial
      lining found around the silicone tube lacks primary inflammatory signs at follow
      up after 1 year, and no signs of compression are seen. It may be an advantage
      because it allows sliding of the repair site against the surrounding tissues.
      Tubes made of bioresorbable material may seem ideal, but they may introduce new
      problems associated with the resorption process in terms of a substantial
      unrestricted macrophage invasion, fibrosis, and disorganized axonal growth. For
      an extended nerve defect, the use of autologous nerve grafts is still the gold
      standard, because no tubular conduit or other conduit has so far proved equal to
      autologous nerve grafts, at least not for reconstruction of human median and
      ulnar nerve trunks. Alternatives other than tubes are currently being developed
      and investigated. For the future, the use of tubes for repair and reconstruction
      of nerves may have interesting potentials, because such a structure allows
      several types of tissue engineering. Various matrices containing, for instance,
      appropriate cells, factors, or other stimulating agents can be introduced in the
      tube lumen and can also be incorporated in a slow-release form in the walls of
      the tube and manipulated. Cultured Schwann cells or other cellular components,
      with or without manipulated production machinery, are probably the cells of
      choice for introduction in the tubes. Tubes may thus prove to be interesting
      alternatives to conventional repair techniques for primary repair of nerves and
      for reconstruction of segmental defects and for neuroma treatment in the future.

PMID- 11525213
TI  - Acceleration of recovery after injury to the peripheral nervous system using
      ultrasound and other therapeutic modalities.
AB  - Taken together, these studies show the promise of various therapeutic modalities
      for the noninvasive treatment of peripheral nerve injury. Further progress on
      these promising methods requires determining the biologic mechanisms responsible
      for the ability of these modalities to enhance peripheral nerve recovery.
      Necessary investigations include validation or refutation of the hypothesis that
      these therapies act on various aspects of the natural healing process. Examples
      include cellular and molecular processes involved in promoting Wallerian
      degeneration and the rate and specificity of axonal regeneration and
      remyelination and muscle reinnervation, processes that are distributed between
      the regenerating nerve itself, the pathway of the regenerating axon, and the
      target of the regenerating nerve. An increased understanding of the biologic
      mechanisms underlying the enhancement of peripheral nerve recovery after injury
      would lend greater insight into the cellular and molecular mechanisms involved in
      successful nerve regeneration and muscle reinnervation. This increased
      understanding may also result in clinically beneficial treatments for peripheral
      nerve disorders.

PMID- 11525214
TI  - Changing spectrum of invasive candidiasis and its therapeutic implications.
AB  - Emerging trends in invasive candidiasis are notable for a dramatic increase in
      infections due to non-albicans Candida species. An increasing number of
      immunocompromised patients at risk from fungal infections, an overall greater
      acuity of illness in the hospitalized patients, particularly those in the
      critical care units, escalating rates of broad-spectrum antibiotic usage, and
      wide utilization of azoles as prophylaxis have probably contributed towards the
      changing epidemiology of invasive candidiasis. Given the inherent decreased
      susceptibility of many of the non-albicans Candida species to currently available
      antifungal agents, these evolving trends have far-reaching clinical relevance.

PMID- 11525215
TI  - Chronic forms of pulmonary aspergillosis.
AB  - Aspergillus is a genus of fungi commonly found in all environments. Remarkably,
      only a few species cause disease and equally remarkably, those same species cause
      multiple diseases. In the lung, exposure to the fungus, the immunological status
      of the individual and the condition of the lung determine the pattern of disease.
      In asthmatic patients and those with cystic fibrosis, allergic bronchopulmonary
      aspergillosis (ABPA) is a complication that reduces pulmonary function and, in
      asthmatics, is substantially improved by itraconazole therapy. Patients with pre
      existing lung cavities develop aspergillomas (fungal masses inside the cavity).
      Aspergillomas carry a 40% 5 years survival, and it not clear whether antifungal
      therapy is helpful. Similar in presentation to aspergilloma is chronic
      necrotizing pulmonary aspergillosis (CNPA). Development of new or expansion of
      existing pulmonary cavities with surrounding paracavitary shadowing is the
      hallmark of CNPA These two entities are probably a continuum of the same
      pathological process. Patients with CNPA respond to systemic antifungal therapy,
      but this may need to be lifelong. Surgery is appropriate for isolated
      aspergillomas, but not pleural or multicavity lesions. Aspergillus empyema is a
      complication of aspergilloma and CNPA, or surgery for these diseases and is slow
      to respond to treatment.

PMID- 11525216
TI  - Critical assessment of issues in the diagnosis of invasive aspergillosis.
AB  - Invasive aspergillosis remains a devastating disease, which is partly because of
      the inability to identify infected patients at an early stage of the disease.
      Recently, new diagnostic tests and procedures have been developed to help in
      identifying high-risk patients. High-resolution computed tomography has been
      shown to be a potent tool for detecting pulmonary abnormalities in neutropenic
      patients. Assays for the detection of circulating markers such as fungal antigens
      or Aspergillus DNA have been developed and show that markers can be detected in
      the blood at an early stage of infection. Also, the markers correlate with the
      fungal burden in the tissue, which allows monitoring of response to antifungal
      therapy. The tests and procedures that are now available need to be incorporated
      into management strategies for at-risk patients and evaluated in clinical trials.
      Although we now have markers that allow the early detection of fungal products,
      many questions remain unanswered with respect to the kinetics of the markers in
      different patient groups, the optimal management strategy and the effect of
      prophylaxis and treatment on the markers. Nevertheless, the implementation of new
      approaches for the management of invasive aspergillosis offers opportunities to
      improve outcome of patients.

PMID- 11525217
TI  - Environmental surveillance and other control measures in the prevention of
      nosocomial fungal infections.
AB  - The steady world-wide increase in the number of severely immunocompromised
      patients in most hospitals has made the control and prevention of nosocomial
      systemic fungal infections a critical quality-of-care standard. Early diagnosis
      and antifungal prophylaxis of these infections are complicated, so avoiding the
      acquisition of the pathogen in the case of Aspergillus and minimizing the
      predisposing risk factors in the case of Candida are more effective approaches.
      The maintenance of good air quality in critical areas in hospitals is mandatory
      to reduce the incidence of invasive aspergillosis. We review the currently
      available Center for Disease Control recommendations and report our own
      experiences in the field. The indications and problems of fungal environmental
      and patient surveillance are also discussed.

PMID- 11525218
TI  - Present status of the detection of antifungal resistance: the perspective from
      both sides of the ocean.
AB  - The NCCLS reference methodology for antifungal susceptibility testing is a new
      milestone of the evolution of medical mycology. The use of this methodology
      however, is not problem-free. At present, major limitations are a trailing
      phenomenon with azoles, unreliable detection of resistance to amphotericin B,
      poor growth of some organisms and unpractical procedures for the clinical
      laboratory. Herein a overview of NCCLS guidelines for yeasts and filamentous
      fungi is presented. Likewise, a review of studies conducted trying to overcome
      the limitations of reference procedures is also included. Several alternative
      approaches are reviewed as alternative media, inoculum size and incubation time.
      Modifications of reading procedure and endpoint determination are also evaluated.
      Agar diffusion methods and other methods for susceptibility testing are cited.
      Finally, we discuss the data on correlation of the in vitro results with the in
      vivo activity.

PMID- 11525219
TI  - Role of early diagnosis and aggressive surgery in the management of invasive
      pulmonary aspergillosis in neutropenic patients.
AB  - Invasive pulmonary aspergillosis (IPA) occurs mostly in immunocompromised hosts
      and especially in neutropenic patients. Improved prognosis for IPA requires early
      diagnosis. We report our experience in the management of IPA in patients with
      hematological malignancies. In prolonged neutropenia (> 10 days), thoracic CT
      scanning seems to be the best choice for the diagnosis of IPA (with CT halo or
      air-crescent signs). Its systematic use allows a dramatic reduction in the time
      to achieve the diagnosis, if there is evidence of a halo sign. The systematic
      screening for the detection of Aspergillus antigenemia with an ELISA test is
      helpful for early diagnosis. The detection of Aspergillus antigen (with the less
      sensitive latex agglutination test) on bronchoalveolar lavage (BAL) fluid may
      also be as useful. The treatment of IPA relies on amphotericin B (or its lipid
      formulations) or on azole antifungal agents. Pulmonary surgical resection should
      be considered either as an emergency procedure (despite persistent neutropenia)
      to avoid massive hemoptysis, or as an elective or diagnostic procedure. This
      global strategy for the management of IPA is associated with a 75-80% success
      rate in hematological patients. Nevertheless, the control of underlying
      malignancy remains a major prognostic factor.

PMID- 11525220
TI  - Granulocyte colony-stimulating factor and other cytokines in antifungal therapy.
AB  - Invasive fungal infections (IFIs) have emerged as a serious threat in
      immunocompromised patients during the last two decades. Host defenses including
      appropriate cytokine responses and intact phagocytic function are necessary to
      combat IFIs. Several cytokines have been investigated and developed for
      preventive and therapeutic use. Among them, granulocyte colony-stimulating factor
      (G-CSF) has been mostly studied and used for various purposes, the most important
      being the faster recovery from neutropenia. Other cytokines with potential
      clinical significance in relation to IFI are granulocyte-macrophage colony
      stimulating factor (GM-CSF), interferon-gamma (IFN-gamma) and macrophage colony
      stimulating factor. Supported by a large number of preclinical studies but
      limited clinical results their potential utility against IFI has been suggested.
      In this review, certain questions related to this issue are discussed based on
      data already available and an attempt to consider future research is made.

PMID- 11525221
TI  - Liposomal amphotericin B (AmBisome) for fungal infections in immunocompromised
      adults and children.
AB  - Invasive fungal infections are rare but life-threatening infections, most often
      occurring in immunocompromised patients. For a long time, Amphotericin B has been
      the best choice for treatment, because it is fungicidal with a broad antifungal
      spectrum and minimal risk of resistance development. The therapeutic use of
      amphotericin B has, however, been limited by its toxicity-both acute as well as
      chronic. To counter this, amphotericin B has been encapsulated in liposomes,
      which reduces its toxicity and allows higher doses to be given. Ambisome is a
      true, spherical, small unilamellar liposome with a median size of 80 nm. The
      pharmacokinetic profile was changed, and the maximum concentration and AUC of
      amphotericin B after AmBisome treatment were greater than those found with the
      conventional drug. The highest tissue concentrations of AmBisome were found in
      the liver and spleen, and less than 1% of the administered dose was recovered in
      other organs. At Huddinge University Hospital, we were the first to use and
      report on the experience of AmBisome. We now have more than 12 years' experience
      in transplant recipients, with a good safety profile, improved rate of curing
      mycological proven infections and reduced mortality in fungal infections. In two
      placebo-controlled prophylactic trials, we found that AmBisome was effective for
      preventing fungal colonization and invasive fungal infections, respectively, in
      allogeneic stem cell and liver transplantation. In uncontrolled and, more
      recently, in randomized controlled studies at other centers, AmBisome has
      revealed less toxicity and an efficacy equal or superior to that of the
      conventional drug in treating neutropenia-associated fever and proven invasive
      fungal infections in both adults as well as in children. Although investigators
      tend to increase the dose used, the optimal dose for probable or proven infection
      is still under debate. Based on our own experience in using AmBisome and the
      experience at other centers, we can conclude that AmBisome represents a major
      breakthrough in the treatment of invasive fungal infections, especially in
      immunocompromised patients.

PMID- 11525222
TI  - Uncommon opportunistic fungi: new nosocomial threats.
AB  - During the past two decades opportunistic fungal infections have emerged as
      important causes of morbidity and mortality in patients with severe underlying
      illnesses and compromised host defenses. While Aspergillus and Candida spp.
      collectively account for the majority of these infections, recent epidemiological
      trends indicate a shift towards infections by Aspergillus spp., nonalbicans
      Candida spp., as well as previously uncommon opportunistic fungi. Apart from an
      expanding number of different Zygomycetes, previously uncommon hyaline
      filamentous fungi (such as Fusarium species, Acremonium species, Paecilomyces
      species, Pseudallescheria boydii, and Scedosporium prolificans), dematiaceous
      filamentous fungi (such as Bipolaris species, Cladophialophora bantiana,
      Dactylaria gallopava, Exophiala species, and Alternaria species) and yeast-like
      pathogens (such as Trichosporon species, Blastoschizomyces capitatus, Malassezia
      species, Rhodotorula rubra and others) are increasingly encountered as causing
      life threatening invasive infections that are often refractory to conventional
      therapies. On the basis of past and current trends, the spectrum of fungal
      pathogens will continue to evolve in the settings of an expanding population of
      immunocompromised hosts, selective antifungal pressures, and shifting conditions
      in hospitals and the environment. An expanded and refined drug arsenal, further
      elucidation of pathogenesis and resistance mechanisms, establishment of in
      vitro/in vivo correlations, incorporation of pharmacodynamics, combination- and
      immunotherapies offer hope for substantial progress in prevention and treatment.

PMID- 11525223
TI  - Advances in invasive fungal infection and antifungal therapy: Introduction.

PMID- 11525224
TI  - Reasons for extraction by dental practitioners in England and Wales: a comparison
      with 1986 and variations between regions.
AB  - OBJECTIVES: To compare reasons for extraction in 1997 and 1986, and to consider
      regional variations for the 1997 data. METHODS: Random samples of general dental
      practitioners (GDPs) completed questionnaires for all extractions for 4 weeks in
      1986 and in 1997. Reasons for extraction by region were compared for the 1997
      data. RESULTS: 220 and 562 GDPs participated in 1986 and 1997, respectively,
      averaging 24 extractions in 1986 and 20 in 1997. 'Caries' remained the commonest
      reason for < or =50-year-olds (excluding 'ortho'), but peaked a decade later than
      in 1986. One-third of 'perio' extractions in both studies were for 51-60-year
      olds, but in 1997 there were fewer such extractions for < or =40-year-olds and
      more for >70-year-olds than in 1986. In 1997 'caries' and 'perio' extractions
      remained equally common for patients >50 years, but there were far more
      extractions for both reasons for >80-year-olds. Patients < or =30 years in S.
      England and in the Midlands/E. Anglia had more 'ortho' than 'caries' extractions,
      whereas 'caries' predominated in N. England and in Wales. 'Caries' exceeded
      'perio' for patients >40 years in Wales, whereas in the three English regions the
      two reasons were equally frequent. CONCLUSIONS: Comparisons of results of two
      studies conducted a decade apart indicate that there have been some changes in
      reasons for extraction. Overall, mean number of extractions per dentist has
      declined, and it appears that the trend is for extractions due to the common
      dental diseases to be carried out later in life. The 1997 data also suggest that
      young patients in Wales and N. England are relatively disadvantaged, having more
      caries and less orthodontic treatment than those in other parts of England.

PMID- 11525225
TI  - Can dentures improve the quality of life of those who have experienced
      considerable tooth loss?
AB  - OBJECTIVES: The aim of this study was to identify variations in the impact of
      oral health on quality of life (OHQOL) among UK residents in relation to self
      reported number of teeth possessed and denture status. In addition, to determine
      whether recourse to a removable prosthesis for those who claimed that they had
      experienced considerable tooth loss (having <20 teeth) was associated with
      quality of life. METHODS: The vehicle for this was the Office for National
      Statistics Omnibus survey in Great Britain. A random probability sample of 2667
      addresses was selected in a multistage sampling process. Participants were
      interviewed about their oral health status. The impact of oral health on quality
      of life was measured utilising the OHQoL-UK(W) measure. RESULTS: The response
      rate was 68%. Variations in OHQoL-UK(W) scores were apparent in relation to self
      reported number of teeth possessed (P < 0.001) and denture status (P < 0.001).
      Moreover, disparities in OHQOL were apparent among those who experienced
      considerable tooth loss who didn't have recourse to a denture (P < 0.001). In
      regression analysis, those who claimed that they had <20 natural teeth but had no
      recourse to a denture were less than half as likely to enjoy enhanced oral health
      related quality of life compared to others in the population (OR = 0.46, 95% Cl
      0.30, 0.71), controlling for socio-demographic factors. CONCLUSIONS: Experience
      of considerable tooth loss without recourse to a removable dental prosthesis is
      an important predictor of oral health related quality of life, as captured by
      OHQoL-UK(W), and associated with reduced quality of life.

PMID- 11525226
TI  - Prevention of pit and fissure caries using an antimicrobial varnish: 9 month
      clinical evaluation.
AB  - OBJECTIVE: The purpose of this study was to determine whether Cervitec--a
      chlorhexidine--containing varnish could reduce the development of pit and fissure
      caries in children. METHODS: One hundred children each in age groups 7-8 and 12
      14 years were selected from schools in Riyadh, Saudi Arabia. To be included in
      the study, each child had to have at least two sound contra-lateral first or
      second permanent molars with deep fissures. A split mouth method was used with
      one test tooth and one control within the same jaw. The left or the right side
      was selected randomly for test or control. The plaque samples from the occlusal
      surfaces of the test and control and the saliva samples were collected at
      baseline examination and after 9 months to estimate the number of Streptococcus
      mutans by the strip mutans method of Jensen and Bratthall (Jensen B, Bratthall D.
      A new method for the estimation of mutans streptococci in human saliva. Journal
      of Dental Research 1989;68:468-471). Cervitec varnish containing 1% chlorhexidine
      (CHx) and thymol was applied at baseline, at 3-4 months and at 6 months to the
      test tooth after isolation while the control had prophylaxis using cotton pellet
      in water each time the varnish was applied to the test tooth. Caries examination
      of the test and control followed after 9 months, according to the criteria and
      methods of WHO (World Health Organization. Oral Health Surveys. Basic Methods 4th
      ed., Geneva, WHO 1997). The blind technique was used in the diagnosis of caries
      and in the examination of the S. mutans count at the end of the study. RESULTS:
      Ninety four of the 7-8 year old and 86 of the 12-14 year old children completed
      the study. The results showed that the caries increment in both control groups of
      teeth after 9 months is significantly higher than in the test teeth (McNemar
      test: chi2 = 11.60, P < 0.001). The rate of caries development in a fissure was
      significantly correlated to the plaque mutans score of that fissure and there was
      considerable reduction in the S. mutans count of the plaque in the test teeth
      compared with the control (Spearman Rank Correlation: P < 0.001). CONCLUSION: It
      is concluded that the CHx varnish reduced the development of fissure caries
      significantly.

PMID- 11525227
TI  - The effect of fluoridated and non-fluoridated rewetting agents on in vitro
      recurrent caries.
AB  - OBJECTIVE: This study examined the in vitro caries inhibiting potential of
      fluoridated and non-fluoridated rewetting agents that are applied to acid-etched
      enamel and dentine before the use of a water-free, dentine adhesive. MATERIALS
      AND METHODS: Twelve caries-free premolars were divided into three groups of four
      teeth each. 2 x 3 x 1.5 mm cavities were prepared on the mesial and distal
      surfaces of each tooth, with half of the cavosurface margin in enamel and half in
      root dentine. In Group I (control), One-Step (Bisco, Schaumburg, USA) was applied
      without etching or rewetting agents. In Group II, cavities were acid-etched,
      rinsed, dried, and rewetted with Aqua-Prep (Bisco), a non-fluoridated rewetting
      agent, and then bonded with One-Step. Treatment for Group III was similar to
      Group II, except that Aqua-Prep F (Bisco), a fluoridated rewetting agent was
      used. Bonded cavities were restored with a non-fluoride-containing flowable
      composite (AEliteFlo, Bisco). Artificial carious lesions were induced in these
      specimens, from which multiple 100+/-20 microm thick longitudinal sections were
      prepared, yielding 16 specimens per group for evaluation with polarised light
      microscopy (PLM) and microradiography (MRG). Representative sections were
      processed for transmission electron microscopy (TEM) examination and scanning
      transmission electron microscopy/energy dispersive X-ray (STEM/EDX) analyses.
      RESULTS: The differences in demineralisation of dentine among the groups were not
      statistically significant for 'relative' lesion depth (p > 0.05, ANOVA, Student
      Neuman-Keuls test), but highly significant for 'relative' lesion area (p <
      0.001). Wall lesions were consistently present in Group I, while inhibition zones
      were invariably observed in Group III. 87.5% of Group II specimens exhibited
      neither wall lesion nor inhibition zone. TEM showed that remnant dentine apatite
      crystallites within the inhibition zones in Group III were larger and denser than
      those present within the corresponding wall lesions. STEM/EDX analyses confirmed
      the presence of calcium, phosphorus and fluorine in these plate-like
      crystallites. CONCLUSION: When used with a water-free, single-bottle dentine
      adhesive, a non-fluoridated rewetting agent is able to reduce, but cannot
      completely prevent recurrent caries. The use of a fluoridated rewetting agent is
      useful under the situation when microleakage occurs, by providing the additional
      benefit of fluoride-induced demineralisation inhibition.

PMID- 11525228
TI  - A randomised, controlled and blinded histological and immunohistochemical
      investigation of Carisolv on pulp tissue.
AB  - OBJECTIVES: This investigation was undertaken to test the hypothesis that
      Carisolv would show the same safety profile as physiologic saline when in direct
      contact with pulp tissue for 30 min. Furthermore, the sensory nerve fibre
      reaction in response to the injury was evaluated. METHODS: Incisors and molars in
      40 Sprague-Dawley rats were opened and the pulp tissue randomly exposed to either
      Carisolv or NaCl for 30 min. Observation periods ranged from I day to I week.
      RESULTS: Light microscopic examination showed an almost identical cellular
      response in both test teeth and controls, which consisted of a localised
      inflammation represented predominantly by macrophages. Immunohistochemistry
      revealed an accumulation of beaded CGRP-immunoreactive fibres in immediate
      vicinity of the lesion, suggesting that the nerves had emitted small sprouts.
      Some fibres at this location were SP-positive, but very few, or no nerve fibres,
      displayed NPY-immunoreactivity. This innervation pattern was seen in both test
      and controls in similar distribution and at similar intensity. CONCLUSIONS:
      Results obtained in this study suggests the hypothesis to be valid, i.e. Carisolv
      does not seem to add appreciable adverse effects over and beyond what is caused
      by the experimental procedures. Furthermore, Carisolv does not seem to influence
      the distribution or neuropeptide expression of sensory nerve fibres in the pulp.

PMID- 11525229
TI  - Histocytological evaluation of the reaction of rat pulp tissue to Carisolv.
AB  - OBJECTIVES: Carisolv is a viscous substance for the chemo-mechanical removal of
      caries. The aim of this study was to examine the tissue reactions of pulp and
      dentin tissue to Carisolv in vivo. METHODS: In 48 caries-free molars (24 Wistar
      rats, age: 3 months) an occlusal cavity was prepared. The roofs of the pulp
      chambers were perforated with a sharp probe and Carisolv solution was placed onto
      the exposed pulp of 24 molars for 1, 10 and 20 min. Twenty-four contralateral
      molars served as controls and were coated with an inert liquid containing
      isotonic saline solution, carmellose and erythrosin. RESULTS: After a contact
      period of 10 and 20 min in the experimental group, pulpal destruction of
      intercellular substance and cells including odontoblasts was observed up to a
      depth of 150 microm, in addition to the mechanical damage by perforation (e.g.
      dentin particles). The pulpal and predentin fibrils as well as the dentin fibrils
      appeared to be intact and did not differ from the controls. After a contact time
      of 1 min a weaker damage of pulp cells and odontoblasts, as well as intact
      fibrils in pulp, predentin and dentin could be observed. CONCLUSIONS: Radicals of
      Carisolv (OH- and OCI-) cause alkaline hydrolysis of cellular components but do
      not decompose collagenous tissue components.

PMID- 11525230
TI  - A laboratory investigation of the role of guide planes in the retention of cast
      cobalt-chromium alloy partial denture frameworks.
AB  - OBJECTIVES: This in vitro study examined the resistance to displacement offered
      by guide planes and the displacement mechanics of a bilateral bounded saddle cast
      cobalt chrome alloy removable partial denture framework under conditions
      simulating an average initial fit. METHODS: A specially designed model mouth jig
      fitted with strain gauges to monitor the forces across the guiding plane/guiding
      surface interfaces was used. Guiding planes of enamel, silver tin amalgam and
      dental composite with seven combinations of guide planes and three angles of
      withdrawal were examined. Guiding plane size was also examined for dental enamel.
      RESULTS: A statistically significant difference in retention was found for all
      factors examined. Retention increased with increasing angle of withdrawal. Size
      effects were found but considered unreliable. CONCLUSIONS: It was concluded that
      with a tight fit guiding plane retention may be readily predicted for any given
      material, combination of mesial, distal and lingual guiding planes and angulation
      conditions by the application of mechanical principles providing the basic
      parameters are known. Attention is drawn to the reasons for further work to fully
      understand the clinical situation.

PMID- 11525231
TI  - Fluoride release/uptake of conventional and resin-modified glass ionomers, and
      compomers.
AB  - OBJECTIVES: To assess the levels of fluoride ions released from a range of
      freshly-prepared aesthetic restorative materials, and then the effects of a
      topical acidulated phosphate fluoride (APF) gel. METHODS: Five specimens each of
      four conventional GICs, two resin-modified GICs, two compomers, and a resin
      composite (control) were assessed for their fluoride ion release over 6 weeks,
      before being exposed to 1.23% APF gel for 4 min and then measuring their fluoride
      ion levels for another 6 weeks. RESULTS: Following an initial brief, variable
      burst of fluoride ion release, the rates then fell quickly for most materials
      and, although high rates of fluoride ion release were measured immediately
      following the application of APF gel, these rates also fell quickly for most
      materials. After 12 weeks, the mean fluoride ion levels were much lower than
      immediately before gel application. The APF gel treatment caused surface damage
      to all materials, especially to the conventional GICs. CONCLUSION: The results of
      this study suggested that much of the increased fluoride ion release found
      following topical exposure of the fluoridated restorative materials to APF gel
      was caused by surface effects rather than by chemical recharging.

PMID- 11525232
TI  - Local and systemic effects of Na+/K+ATPase inhibition.
AB  - The positive inotropic and electrophysiological effects of cardiac glycosides on
      cardiac muscle are mediated through inhibition of Na+/K+ ATPase by binding to a
      specific extracytoplasmic site of the a-subunit of this enzyme. The inhibition of
      Na+/K+ ATPase affects ionic flux and produces direct local effects on cardiac
      contractility, electrical excitability and conduction, but also profound systemic
      effects mainly as a result of haemodynamic changes. These effects are responsible
      for beneficial therapeutic as well as toxic effects. Inhibition of Na+/K+ ATPase
      results in potentiation of K+ loss from cells and Na+ entry into cells, so
      consequently affects action potential generation and propagation. This also
      underlines the potentiation of certain effects of cardiac glycosides by
      hypokalemia and hypomagnesaemia, and the effects of changes in calcium
      homeostasis on the cardiac glycoside pharmacodynamics. Furthermore, inhibition of
      Na+/Ca++ exchange enhances Ca++ mobilization and promotes contractility. These
      effects (locally and systemically) differ greatly, depending on the haemodynamic
      status and myocardial oxygen supply. Cardiac glycosides have less affinity for
      Na+/K+ ATPases at other sites (e.g. skeletal muscle), but some extracardiac
      effects (vascular effects, effects on colour vision, CNS and autonomic effects,
      renal effects) may be related to Na+/K+ ATPase inhibition.

PMID- 11525233
TI  - Treatment of congestive heart failure--current status of use of digitoxin.
AB  - Digitalis glycosides exert a positive inotropic effect, i.e. an increase in
      myocardial contractility associated with a prolongation of relaxation period, and
      glycosides lower the heart rate (negative chronotropic), impede stimulus
      conduction (negative dromotropic) and promote myocardial excitability (positive
      bathmotropic). They seem to influence the activities of both the vagal and the
      sympathetic systems. Digitalis glycosides that belong to different substance
      classes are closely comparable concerning pharmacodynamics but differ
      substantially in regard to pharmacokinetics. Digoxin and its derivatives are less
      lipophilic, show lower protein binding and shorter half-life, are mainly
      eliminated via the kidney and accumulate rather rapidly in cases of insufficient
      kidney function. Digitoxin is highly lipophilic and extensively bound to plasma
      proteins, has a longer half-life, is mainly eliminated in the metabolized state
      via urine and faeces and does not accumulate in kidney dysfunction. As a result
      of a more stable pharmacokinetic profile, the incidence of toxic side effects
      seems to be lower with digitoxin than with digoxin. Since the beginning of the
      1990s, the antagonists of the RAAS qualified as the standard treatment for
      congestive heart failure, often in combination with diuretics, vasodilators or
      beta-antagonists. However, the important role of digitalis glycosides as
      therapeutic comedication or alternative was never denied, especially in atrial
      fibrillation with tachycardia. The PROVED and RADIANCE trials proved a
      detrimental effect of the withdrawal of digoxin therapy on exercise capacity,
      left-ventricular ejection fraction and clinical symptoms. The DIG trial revealed
      that digoxin comedication in sinus rhythm patients with congestive heart failure
      was associated with a lower morbidity (as taken from death or hospitalization
      because of worsening heart failure) and an unchanged overall mortality--being a
      unique feature among the available inotropic drugs. Comparable studies for
      digitoxin have not yet been performed but, because of its higher pharmacological
      stability, it might well be associated with even more advantages in this regard
      than digoxin.

PMID- 11525234
TI  - Ambulatory blood pressure in heart failure.
AB  - Ambulatory blood-pressure monitoring (ABPM) is accepted in the evaluation and
      management of hypertension. The use of ABPM in heart failure has received
      considerably less attention. Many patients with advanced heart failure experience
      disabling fatigue, orthostatic dizziness and symptoms of coronary and
      cerebrovascular insufficiency that may relate to periods of hypotension. These
      may be exacerbated by vasodilator drug therapy and may be difficult to evaluate
      by casual clinic recordings. ABPM in heart failure may help in the following: (i)
      evaluating time-dependent pharmacodynamic drug effects, such as peak and end-of
      dose phenomena, tolerance and rebound; (ii) titrating ACE inhibitors and other
      drugs to highest-tolerated doses; and (iii) correlating circadian blood-pressure
      profiles with symptoms, quality of life, severity of heart failure, progression
      of ventricular and renal dysfunction, risks of stroke and myocardial infarction,
      and life expectancy. Devices for ABPM have been beset by problems of inaccuracy
      and unreliability. Standards for their manufacture and sale (including bench
      tests of accuracy against sphygmomanometry and intra-arterial recordings, and
      field tests of reliability) have been devised independently by several agencies,
      including the British Hypertension Society (BHS) and US Association for the
      Advancement of Medical Instrumentation (AAMI). A joint BHS/AAMI set of guidelines
      is in preparation. These guidelines emphasize the suitability of ABPM devices for
      hypertensive patients and those under general anesthesia, and may not be
      applicable to ambulant individuals with heart failure and blood pressures at or
      below the lower end of the evaluated ranges. Prospective studies of the accuracy
      and reliability of ABPM devices, their clinical utility and research potential
      should be undertaken in patients with heart failure before their informal and
      uncontrolled use in this population becomes widespread.

PMID- 11525235
TI  - Effects of cardiac glycosides on 24-h ambulatory blood pressure in healthy
      volunteers and patients with heart failure.
AB  - Blood pressure effects of cardiac glycosides in humans have been infrequently
      reported. Although direct infusion of ouabain or digoxin causes vasoconstriction,
      indirect effects of cardiac glycosides may have the opposite effect, owing to
      changes in sympatho-vagal balance. This paper summarises three studies on the
      effects of cardiac glycosides on circadian blood pressure, utilizing automatic 24
      h ambulatory blood pressure measurement (ABPM). In healthy volunteers, 10 days of
      oral digoxin or digitoxin caused decreases in diastolic blood pressure and heart
      rate during overnight sleep. No effect was detectable during daytime activities.
      In patients with heart failure (NYHA stage II), 7 days of oral digoxin also
      caused a decrease in diastolic blood pressure but only a small increase in
      systolic pressure during overnight sleep. Again, no effect was detectable during
      the day. Cardiac glycosides have significant effects on blood pressure, which
      only appear during overnight sleep, i.e. a phase when sympathetic background
      activity is lowest. Regular daytime activities may 'overwrite' these effects.
      Effects of cardiac glycosides on blood pressure may have therapeutic impact,
      depending on the stage of heart failure and concomitant diseases.

PMID- 11525236
TI  - Pressor and vascular effects of cardiac glycosides.
AB  - BACKGROUND: For the past two decades, it has generally been accepted ('Blaustein
      hypothesis') that cardiac glycosides such as ouabain and digoxin increase the
      sodium and calcium content of smooth muscle cells, so inducing arterial
      vasoconstriction and a rise in blood pressure. Recent data from an experimental
      study we carried out led us to question this assumption. DESIGN: A retrospective
      literature survey covering 20 years and including animal and human studies was
      performed. Representative results are presented. RESULTS: Contradictory effects
      of cardiac glycosides on blood pressure and vasculature have been described.
      Increased, decreased or unaltered blood-pressure values have been observed
      following administration of the glycosides ouabain, digoxin and digitoxin.
      Moreover, vasoconstricting as well as vasodilating effects of cardiac glycosides
      have been demonstrated. Several recent studies show that cardiac glycosides such
      as digoxin and digitoxin can lead to a reduction of at least diastolic blood
      pressure. CONCLUSION: A slight vasodilation of resistance vessels followed by a
      fall in diastolic blood pressure could be a contributing factor for the
      beneficial effects of cardiac glycosides in patients with congestive heart
      failure. This vasodilation may be caused by central (neurohumoral) effects of
      digitalis glycosides.

PMID- 11525237
TI  - Self-cytoprotection against stress: feedback regulation of heme-dependent
      metabolism.
AB  - This minireview provides insight into feedback regulation of heme-dependent
      metabolism as a defensive cellular response against stress. Interactions among
      heme-, iron-, porphyrin-, and CO/NO-dependent metabolic pathways during the
      stress-induced response are emphasized in the context of feedback regulation. The
      hypothetical model of the latter interactions is presented as tightly controlled
      feedback cycles.

PMID- 11525239
TI  - AlphaB-crystallin, a low-molecular-weight heat shock protein, acts as a regulator
      of platelet function.
AB  - It has recently been reported that alphaB-crystallin, a low-molecular-weight heat
      shock protein, may be released from cells by mechanical stretch. We investigated
      a physiological role of alphaB-crystallin in platelet function. AlphaB-crystallin
      inhibited platelet aggregation induced by thrombin or botrocetin in hamsters and
      humans. These platelets had specific binding sites for alphaB-crystallin.
      Moreover, alphaB-crystallin significantly reduced thrombin-induced Ca2+ influx
      and phosphoinositide hydrolysis by phospholipase C in human platelets.
      Additionally, plasma levels of alphaB-crystallin were markedly elevated in
      cardiomyopathic hamsters. Levels of alphaB-crystallin in vessel walls after
      endothelial injury were markedly reduced. Therefore, our results suggest that
      alphaB-crystallin, which is discharged from vessel walls in response to
      endothelial injury, acts intercellularly as a regulator of platelet function.

PMID- 11525238
TI  - Protein kinase inhibitors can suppress stress-induced dissociation of Hsp27.
AB  - We previously showed that the aggregated form of Hsp27 in cultured cells becomes
      dissociated as a result of phosphorylation with various types of stress. In order
      to clarify the signal transduction cascade involved, the effects of various
      inhibitors of protein kinases and dithiothreitol on the dissociation of Hsp27
      were here examined by means of an immunoassay after fractionation of cell
      extracts by sucrose density gradient centrifugation. The dissociation of Hsp27
      induced by exposure of U251 MG human glioma cells to metals (NaAsO2 and CdCl2),
      hypertonic stress (sorbitol and NaCI), or anisomycin, an activator of p38 mitogen
      activated protein (MAP) kinase, was completely suppressed by the presence of SB
      203580 or PD 169316, inhibitors of p38 MAP kinase, but not by PD 98059 and Uo
      126, inhibitors of MAP kinase kinase (MEK), nor by staurosporine, Go 6983, and
      bisindolylmaleimide I, inhibitors of protein kinase C. Phorbol ester (PMA)
      induced dissociation of Hsp27 was completely suppressed by staurosporine, Go
      6983, or bisindolylmaleimide I and partially suppressed by SB 203580, or PD
      169316 but not by PD 98059 or Uo 126, indicating mediation by 2 cascades. The
      presence of 1 mM dithiothreitol in the culture medium during exposure to
      chemicals suppressed the dissociation of Hsp27 induced by arsenite and CdCl2 but
      not by other chemicals. These results suggest that the phosphorylation of Hsp27
      is catalyzed by 2 protein kinases, p38 MAP kinase-activated protein (MAPKAP)
      kinase-2/3 and protein kinase C. In addition, metal-induced signals are sensitive
      to reducing power.

PMID- 11525240
TI  - DnaK/DnaJ chaperone system reactivates endogenous E. coli thermostable FBP
      aldolase in vivo and in vitro; the effect is enhanced by GroE heat shock
      proteins.
AB  - Thermally aggregated, endogenous proteins in Escherichia coli cells form the S
      fraction, which is separable by sucrose density gradient centrifugation. To date,
      relatively little is known about the mechanisms of elimination of the heat
      aggregated proteins from E. coli cells and the composition of the S fraction. We
      have identified several proteins of the S fraction using 2D-gel electrophoresis
      and microsequencing. A thermostable II class fructose-1,6-bisphosphate aldolase
      (Fda protein) appeared to be one of numerous proteins of the S fraction. Fda was
      purified from E. coli overproducer strain and used as a model substrate for
      investigation of the role of Hsps in prevention and repair of thermal
      denaturation of proteins both in vivo and in vitro. We found that the heat
      inactivation of Fda was reversible and that its reactivation in vivo and in vitro
      required mainly the assistance of the DnaK/DnaJ chaperone system. The dnaK756 and
      dnaJ259 mutations had a negative effect on the reactivation of thermally
      inactivated Fda. Moreover, we showed that the reactivation process in vitro was
      enhanced when GroEL/GroES were added together with DnaK/DnaJ. GroEL/GroES alone
      were inefficient in the resolubilization or reactivation of the heat-aggregated
      Fda. It is supposed that the denaturation of the thermostable Fda in vivo results
      rather from a temporary and transient deficit of Hsps than from the direct heat
      effect.

PMID- 11525241
TI  - Expression of the chaperonin 10 gene during zebrafish development.
AB  - We have isolated a cDNA encoding chaperonin 10 (cpn10) from the zebrafish. Using
      northern, western, and in situ hybridization analysis, we observed that the cpn10
      gene is expressed uniformly and ubiquitously throughout embryonic development of
      the zebrafish. Upregulation of cpn10 expression was observed following exposure
      of zebrafish embryos to a heat shock of 1 hour at 37 degrees C compared to
      control embryos raised at 27 degrees C. The extracellular form of Cpn10 called
      early pregnancy factor (EPF), found in the serum of pregnant mammals, was not
      detected in the serum of either male or female zebrafish. These expression
      studies suggest that Cpn10 plays a general role in zebrafish development as well
      as being consistent with the hypothesis that EPF is involved in the embryo
      implantation process in mammals.

PMID- 11525242
TI  - Effects of schisandrin B pretreatment on tumor necrosis factor-alpha induced
      apoptosis and Hsp70 expression in mouse liver.
AB  - Tumor necrosis factor-alpha (TNFalpha) could cause apoptosis in hepatic tissue of
      D-galactosamine sensitized mice, as evidenced by the increase in the extent of
      DNA fragmentation. The hepatic apoptosis induced by TNFalpha was associated with
      hepatocellular damage as assessed by plasma alanine aminotransferase activity.
      Schisandrin B (Sch B) pretreatment at daily doses ranging from 0.5 to 2 mmol/kg
      for 3 days caused a dose-dependent protection against TNFalpha-induced apoptosis
      in mice. The hepatoprotection was accompanied by a parallel reduction in the
      extent of hepatocellular damage. The same Sch B pretreatment regimens increased
      hepatic Hsp70 level in a dose-dependent manner. The relevance of Sch B-induced
      increase in Hsp70 expression to the prevention of TNFalpha-triggered hepatic
      apoptosis remains to be elucidated.

PMID- 11525243
TI  - Hsp27 protects mitochondria of thermotolerant cells against apoptotic stimuli.
AB  - Enhanced cell survival and resistance to apoptosis during thermotolerance
      correlates with an increased expression of heat shock proteins (Hsps). Here we
      present additional evidence in support of the hypothesis that the induction of
      Hsp27 and Hsp72 during acquired thermotolerance in Jurkat T-lymphocytes prevents
      apoptosis. In thermotolerant cells, Hsp27 was shown to associate with the
      mitochondrial fraction, and inhibition of Hsp27 induction during thermotolerance
      in cells transfected with hsp27 antisense potentiated mitochondrial cytochrome c
      release after exposure to various apoptotic stimuli, despite the presence of
      elevated levels of Hsp72. Caspase activation and apoptosis were inhibited under
      these conditions. In vitro studies revealed that recombinant Hsp72 more
      efficiently blocked cytochrome c-mediated caspase activation than did recombinant
      Hsp27. A model is presented for the inhibition of apoptosis during
      thermotolerance in which Hsp27 preferentially blocks mitochondrial cytochrome c
      release, whereas Hsp72 interferes with apoptosomal caspase activation.

PMID- 11525245
TI  - Arsenite-inducible RNA-associated protein (AIRAP) protects cells from arsenite
      toxicity.
AB  - Exposure of cells to arsenicals activates multiple stress pathways resulting in
      the induction of specific genes whose identity and role in the adaptation to
      arsenical-induced cellular stress are poorly understood. We report here the
      identification of a novel gene encoding an arsenite-inducible, cysteine- and
      histidine-rich RNA-associated protein, AIRAP, that is conserved among mammals,
      Drosophila and C elegans. Immunochemistry and cell fractionation experiments
      indicate that, when induced, AIRAP is present in both the nucleus and the
      cytoplasm, and cross-linking experiments indicate that it associates with RNA in
      vivo. The expression of a C elegans homologue of AIRAP, aip-1, is also induced by
      exposure to arsenite, and expression of an aip-1::gfp transgene is most
      pronounced in hypodermal cells. RNA-mediated interference (RNAi) of aip-1 lowers
      the resistance of nematodes to arsenite yet does not appear to affect viability
      under standard growth conditions. These experiments suggest a role for AIRAP/AIP
      1 in protecting cells from the toxic effects of arsenite.

PMID- 11525244
TI  - Human cyclophilin 40 is a heat shock protein that exhibits altered intracellular
      localization following heat shock.
AB  - The unactivated steroid receptors are chaperoned into a conformation that is
      optimal for binding hormone by a number of heat shock proteins, including Hsp90,
      Hsp70, Hsp40, and the immunophilin, FKBP52 (Hsp56). Together with its partner
      cochaperones, cyclophilin 40 (CyP40) and FKBP51, FKBP52 belongs to a distinct
      group of structurally related immunophilins that modulate steroid receptor
      function through their association with Hsp90. Due to the structural similarity
      between the component immunophilins, FKBP52 and cyclophilin 40, we decided to
      investigate whether CyP40 is also a heat shock protein. Exposure of MCF-7 breast
      cancer cells to elevated temperatures (42 degrees C for 3 hours) resulted in a 75
      fold increase in CyP40 mRNA levels, but no corresponding increase in CyP40
      protein expression, even after 7 hours of heat stress. The use of cycloheximide
      to inhibit protein synthesis revealed that in comparison to MCF-7 cells cultured
      at 37 degrees C, those exposed to heat stress (42 degrees C for 3 hours)
      displayed an elevated rate of degradation of both CyP40 and FKBP52 proteins.
      Concomitantly, the half-life of the CyP40 protein was reduced from more than 24
      hours to just over 8 hours following heat shock. As no alteration in CyP40
      protein levels occurred in cells exposed to heat shock, an elevated rate of
      degradation would imply that CyP40 protein was synthesized at an increased rate,
      hence the designation of human CyP40 as a heat shock protein. Application of heat
      stress elicited a marked redistribution of CyP40 protein in MCF-7 cells from a
      predominantly nucleolar localization, with some nuclear and cytoplasmic staining,
      to a pattern characterized by a pronounced nuclear accumulation of CyP40, with no
      distinguishable nucleolar staining. This increase in nuclear CyP40 possibly
      resulted from a redistribution of cytoplasmic and nucleolar CyP40, as no net
      increase in CyP40 expression levels occurred in response to stress. Exposure of
      MCF-7 cells to actinomycin D for 4 hours resulted in the translocation of the
      nucleolar marker protein, B23, from the nucleolus, with only a small reduction in
      nucleolar CyP40 levels. Under normal growth conditions, MCF-7 cells exhibited an
      apparent colocalization of CyP40 and FKBP52 within the nucleolus.

PMID- 11525246
TI  - The hsp60B gene of Drosophila melanogaster is essential for the spermatid
      individualization process.
AB  - The 60-kDa heat shock protein family (Hsp60) is found in prokaryotes,
      mitochondria, and chloroplasts. The Hsp60 proteins promote proper protein folding
      by preventing aggregation. In Drosophila melanogaster, the hsp60 gene is
      essential for a variety of developmental processes, beginning at early
      embryogenesis. In this study we show that an additional member of the Drosophila
      hsp60 gene family, hsp60B, is essential in male fertility. In males homozygous
      for a mutation of the hsp60B gene, developmental processes appeared normal
      throughout most of spermatogenesis, including spermatocyte growth, meiosis, and
      spermatid elongation. At these stages, mitochondria also displayed a
      differentiation process similar to wild-types. However, we found that the
      mutation disrupted a late stage of spermatogenesis, the spermatid
      individualization process. In this process, the individualization complex is
      assembled at spermatid nuclear heads, traverses along spermatid tails, and
      generates membranes for each of the spermatids in a cyst. Our analysis further
      shows that the individualization complex in sterile males displayed abnormal
      morphology as it was traveling along the spermatid tails. The Drosophila Hsp60
      proteins are believed to be exclusively localized in the mitochondria. Our
      observation that the hsp60B mutation displayed no apparent defect in
      mitochondrial differentiation during spermatogenesis suggests that the Hsp60B
      protein may operate in a nonmitochondrial location.

PMID- 11525248
TI  - Pituitary adenylate cyclase-activating polypeptide hormone (PACAP) at very low
      dosages improves memory in the rat.
AB  - To ascertain whether very low dosages of pituitary adenylate cyclase-activating
      polypeptide (PACAP) influence learning in mammals, immediately after the
      acquisition trial of a passive avoidance response (PAR) paradigm, PACAP-38 was
      administered intracerebroventricularly at increasing dosages (0, 0.02, 0.2, 2,
      20, and 200 ng in 10 microl saline) to different groups of rats. The mnemonic
      effects were measured by means of retention testing 48 and 96 h later. At
      intermediate PACAP-38 concentrations there was a significant mnemonic improvement
      of the PAR. The maximal effect was observed after the 0.2-ng PACAP-38
      administration (longer step-through latencies). There was a lesser effect at the
      subsequent higher concentration, 2 ng. Higher dosages had no effects. It is
      concluded that PACAP-38 acts as an enhancer of mammalian mnemonic processes even
      at very low dosages. The positive effect follows an inverted U-shaped dose
      response curve. The results may be of interest for the therapy of some
      neuropathological conditions.

PMID- 11525249
TI  - Role of the medial and lateral caudate-putamen in mediating an auditory
      conditional response association.
AB  - Rats with quinolinic acid lesions of the medial or lateral caudate-putamen (CPu)
      and controls were tested for performance of a previously learned auditory
      conditional response association task. The task involved the selection of two
      possible responses when presented with one of two different tones. Results
      indicated that lesions of either the medial or the lateral CPu produced a
      sustained deficit in the auditory conditional response association task. Only the
      lateral CPu lesioned rats exhibited transient motor problems immediately
      following surgery, but these problems did not interfere with the execution of the
      appropriate responses. It is suggested that both the medial and the lateral CPu
      are involved in response selection and response separation within egocentric
      space.

PMID- 11525247
TI  - Regulation of the Hsp90-binding immunophilin, cyclophilin 40, is mediated by
      multiple sites for GA-binding protein (GABP).
AB  - Within steroid receptor heterocomplexes the large tetratricopeptide repeat
      containing immunophilins, cyclophilin 40 (CyP40), FKBP51, and FKBP52, target a
      common interaction site in heat shock protein 90 (Hsp90) and act coordinately
      with Hsp90 to modulate receptor activity. The reversible nature of the
      interaction between the immunophilins and Hsp90 suggests that relative cellular
      abundance might be a key determinant of the immunophilin component within steroid
      receptor complexes. To investigate CyP40 gene regulation, we have isolated a 5
      kilobase (kb) 5'-flanking region of the human gene and demonstrated that a
      approximately 50 base pair (bp) sequence adjacent to the transcription start site
      is essential for CyP40 basal expression. Three tandemly arranged Ets sites within
      this critical region were identified as binding elements for the multimeric Ets
      related transcription factor, GA binding protein (GABP). Functional studies of
      this proximal promoter sequence, in combination with mutational analysis,
      confirmed these sites to be crucial for basal promoter function. Furthermore,
      overexpression of both GABP alpha and GABP beta subunits in Cos1 cells resulted
      in increased endogenous CyP40 mRNA levels. Significantly, a parallel increase in
      FKBP52 mRNA expression was not observed, highlighting an important difference in
      the mode of regulation of the CyP40 and FKBP52 genes. Our results identify GABP
      as a key regulator of CyP40 expression. GABP is a common target of mitogen and
      stress-activated pathways and may integrate these diverse extracellular signals
      to regulate CyP40 gene expression.

PMID- 11525250
TI  - The effects of calcium channel antagonists on short- and long-term retention in
      mice using spontaneous alternation behavior.
AB  - The effect of calcium channel antagonists (CCA's) on working and reference memory
      in mice was studied using spontaneous alternation (SA) behavior in a T maze. Mice
      were given either one or four forced trials to either the right or the left arm
      on the training session (T1) followed by a free choice test (T2) at varying
      intervals after the initial trial. Untreated animals given one forced trial
      exhibited significantly greater levels of SA than chance at all delay intervals
      out to 20 min but not at 30, 60, or 180 min. Animals given four forced trials
      showed significant levels of SA 24 h after exposure but not at 72 h. Additional
      groups of mice were treated with amlodipine, nimodipine, diltiazem, and verapamil
      1 h before T1. Mice given one forced trial were tested 30, 60, or 180 min after
      T1 while mice given four forced trials were tested 72 h after T1. Results showed
      that all of the CCA's except verapamil produced significant SA at the 30-min
      interval and nimodipine and diltiazem also significantly increased SA at the 60
      min-delay interval. No significant effects were observed at the 180-min test. In
      the four trial groups, all of the CCA's with the exception of verapamil produced
      significant levels of SA at the 72-h interval. These results indicate that
      representative CCA's from both the dihydropyridine and the benzothiazapine
      classes can facilitate both short- and long-interval SA, thereby providing
      further confirmation that CCA's can enhance memory processing in young animals.

PMID- 11525251
TI  - Effects of neocortical ectopias and environmental enrichment on Hebb-Williams
      maze learning in BXSB mice.
AB  - Approximately 40-60% of BXSB mice have neocortical ectopias, a developmental
      anomaly characterized by migration of neurons into the neuron-sparse layer I of
      cortex. Previous studies have shown that ectopic BXSB mice have superior
      reference, but inferior working, memory on spatial tasks. Female BXSB mice were
      housed either in an enriched environment or in standard cages at weaning.
      Subsequently, these animals were tested on four of the Hebb-Williams mazes in a
      water-based version of this maze. Theoretically, two of the maze configurations
      placed greater emphasis on reference memory to find the goal, whereas the other
      two favored working memory. Ectopics reared in standard housing conditions were
      better than nonectopics on mazes that favored the use of reference memory, but
      poorer on mazes that favored working memory. In contrast, subjects raised in the
      enriched environment showed no ectopia differences. A comparison of enriched and
      standard housing conditions found that the enriched animals had better reference
      memory but poorer working memory. The latter effect may be because the enriched
      environment, although more stimulating, did not change in time or space; and
      other researchers have shown that daily replacement of stimuli in complex
      environments is correlated with better working memory.

PMID- 11525252
TI  - Conditioned taste aversion and Ca/calmodulin-dependent kinase II in the
      parabrachial nucleus of rats.
AB  - Bielavska and colleagues (Bielavska, Sacchetti, Baldi, & Tassoni, 1999) have
      recently shown that KN-62, an inhibitor of calcium/calmodulin-dependent kinase II
      (CaCMK), induces conditioned taste aversion (CTA) when introduced into the
      parabrachial nucleus (PBN) of rats. The aim of the present report was to assess
      whether activity of CaCMK in the PBN is changed during CTA. We induced CTA in one
      group of rats by pairing saccharin consumption with an ip injection of lithium
      chloride. Another group of rats received lithium alone (without being paired with
      saccharin consumption) to test whether lithium has an effect on CaCMK in the PBN,
      independent of those effects due to training. In animals receiving CTA training,
      CaCMK activity in extracts of PBN was reduced by approximately 30% at the
      postacquisition intervals of 12, 24, and 48 h, compared to control animals
      receiving saccharin with saline injection. By 120 h after CTA training, no effect
      on CaCMK was present. At those postacquisition intervals showing CaCMK activity
      effects due to CTA, there were no effects attributable to lithium alone. Lithium
      alone produced only a short-lasting reduction in CaCMK activity (at 20 min a 30%
      decrease, at 60 min a 23% decrease; and at 6, 12, and 24 h no decrease). The time
      course of lithium-induced effects differed markedly from that of CTA training.
      All changes were Ca2+/- -dependent; we did not observe any changes in Ca
      independent activity. CTA effects on CaCMK were selective for PBN, insofar as we
      did not observe any CTA effects on CaCMK in the visual cortex, a brain region
      unrelated to taste pathways. Since CTA produces a relatively long-lasting
      reduction in CaCMK activity (lasting 2 days or more) specifically in the PBN,
      which is critical a relay for taste information, the reduction of CaCMK activity
      may enable the consolidation of taste memory in an aversive situation.

PMID- 11525253
TI  - Habituation of the proleg withdrawal reflex in Manduca sexta does not involve
      changes in motoneuron properties or depression at the sensorimotor synapse.
AB  - Larvae of the hawkmoth, Manduca sexta, exhibit a defensive proleg withdrawal
      reflex in which deflection of mechanosensory hairs on the proleg tip (the planta)
      evokes retraction of the proleg. A previous behavioral study showed that this
      reflex habituates in response to repeated planta hair deflection and exhibits
      several other defining features of habituation. In a semi-intact preparation
      consisting of a proleg and its associated segmental ganglion, repeated deflection
      of a planta hair or electrical stimulation of its sensory neuron causes a neural
      correlate of habituation, manifested as a decrease in the number of action
      potentials evoked in the proleg motor nerve. Monosynaptic connections from planta
      hair sensory neurons to the principal planta retractor motoneuron exhibit several
      forms of activity-dependent plasticity. In the present study we recorded
      intracellularly from this motoneuron during repetitive electrical stimulation of
      a planta hair sensory neuron. The number of action potentials evoked in the
      motoneuron decreased significantly, representing a neural correlate of
      habituation. The motoneuron's resting membrane potential, input resistance. and
      spike threshold measured before and after repetitive stimulation did not differ
      between the stimulated group and a control group. Furthermore, the amplitude of
      the monosynaptic excitatory postsynaptic potential, as well as the magnitude of
      paired-pulse facilitation, evoked in the motoneuron by the sensory neuron did not
      change after repetitive stimulation. These results suggest that depression at the
      sensorimotor synapse does not contribute to reflex habituation. Rather, other
      mechanisms in the ganglion of the stimulated segment, such as changes in
      polysynaptic reflex pathways, appear to be responsible.

PMID- 11525254
TI  - Post-light potentiation at type B to A photoreceptor connections in Hermissenda.
AB  - We investigated whether the long (approximately 30-s) or short (approximately 3
      s) light stimuli that have been used during behavioral training would induce post
      light potentiation (PLP) at the type B to A photoreceptor connections of the
      isolated nervous system of Hermissenda. We found that a single approximately 30-s
      light step induced PLP at these connections relative to both pre-light baseline
      and seawater control preparations, as did a series of nine short (approximately 3
      s) light steps. In addition, a 30-s step of depolarization-elicited type B cell
      activity induced potentiation comparable to that induced by a approximately 30-s
      light step, indicating that light-elicited type B cell activity contributes to
      the induction of PLP. By contrast, even though a series of short (3-s) light
      steps induced potentiation, short steps of depolarization-evoked type B cell
      activity did not. Hence, light-evoked processes other than type B cell
      depolarization or activity (e.g., perhaps intracellular Ca2+ release) also
      contribute to the induction of PLP. Further results suggest that these other
      light-evoked processes interact nonadditively with type B cell activity to
      generate PLP. Some but not all instances of synaptic potentiation were
      accompanied by various changes in parameters of type B cell action potentials and
      afterhyperpolarizing potentials, suggesting diverse underlying mechanisms,
      including increases in neurotransmitter release. Given that the type A cells have
      been proposed to polysynaptically excite the motor neurons that drive phototaxis,
      a light-evoked potentiation of synaptic strength at the inhibitory type B to A
      photoreceptor connections may play a mechanistic role in light-elicited
      nonassociative learning.

PMID- 11525255
TI  - Cognitive performances and locomotor activity following dentate granule cell
      damage in rats: role of lesion extent and type of memory tested.
AB  - Intradentate injection of colchicine is one of the techniques used to destroy
      granule cells. This study compared the behavioral effects of various amounts of
      colchicine (1.0, 3.0, and 6.0 microg; Col 1, Col 3, and Col 6, respectively)
      injected into the dentate gyrus of adult Long-Evans male rats. Starting 10 days
      after lesion surgery, behavioral testing assessed home-cage and open-field
      locomotion, alternation in a T-maze, water-maze, and radial-maze learning
      according to protocols placing emphasis on reference, and working memory. All of
      these tasks are sensitive to hippocampal disruption. Histological verifications
      showed that the extent of the lesions depends on the dose of colchicine (index of
      dentate gyrus shrinkage: -33% in Col 1, -54% in Col 3, and -67% in Col 6 rats).
      Colchicine dose-dependently increased nocturnal home cage activity (an effect
      found 10 days but not 5 months after surgery), but had no significant effect on
      open-field locomotion or T-maze alternation. A dose-dependent reference memory
      impairment was found during the acquisition of spatial navigation in the water
      maze; Col 3 and Col 6 rats were more impaired than Col 1 rats. During the probe
      trial (platform removed), control rats spent a longer distance swimming over the
      platform area than all rats with colchicine lesions. In the working memory
      version of the test, all rats with colchicine lesions showed significant
      deficits. The deficits were larger in Col 3 and Col 6 rats compared to Col 1
      rats. The lesions had no effect on swimming speed. In the radial-maze test, there
      was also a dose-dependent working memory impairment. However, reference memory
      was disrupted in a manner that did not differ among the three groups of lesioned
      rats. Our data are in line with the view that the dentate gyrus plays an
      important role in the acquisition of new information and is an integral neural
      substrate for spatial reference and spatial working memory. They also suggest
      that damage to granule cells might have more pronounced effects on reference than
      on working memory in the radial maze. Finally, they demonstrate that part of the
      variability in the conclusions from previous experiments concerning the role of
      granule cells in cognitive processes, particularly in spatial learning and
      memory, may be due to the type of tests used and/or the extent of the damage
      produced.

PMID- 11525256
TI  - Cell culture model for antiulcerogenic agents.
AB  - To elucidate the mechanisms of antiulcerogenic agents, we established the cell
      culture model derived from rat gastric epithelium. The cultured cells were
      identified as mucus-producing cells by using histological analysis. This culture
      model is useful for investigating the untiulcer effect of various agents and to
      reveal the mechanisms of the drug action. In particular, the ulcer-healing model
      using the cultured monolayer is promising and convenient for the study of several
      growth factors such as HGF as well as antiulcerogenic agents. The effect of
      polaporezinc in the cultured model is introduced.

PMID- 11525257
TI  - Remodeling of extracellular matrix in gastric ulceration.
AB  - The quality of ulcer repair remains crucial for the stability of the injured
      tissue and for preventing recurrence. Therefore, we studied the temporo-spatial
      expression of the fibrillar and basement membrane collagens (types I, III, and
      IV), the collagenase MMP-2 as well as its inhibitor TIMP-1 before and after oral
      administration of basic fibroblast growth factor (b-FGF) over 30 days in acetic
      acid-induced rat gastric ulcers. The alterations and the exact location of the
      mRNA transcripts and their precipitated proteins were visualized by means of
      radioactive in situ hybridization and immunohistochemistry. Our data show that
      hybridization signals of procollagen I could first be identified 2 hours after
      ulcer induction. After 12 hours the ulcer was established and the mRNA was
      enhanced at the ulcer margin. After 24-48 hours the other procollagen transcripts
      were detected and all were further upregulated over the mesenchymal cells of all
      gastric layers up to 21 days, then declined at 30 days. In contrast, MMP-2 became
      prominent after 48 hours and up to 21 days. TIMP-1 was enhanced at 72 hours.
      After oral administration of b-FGF the transcriptional activity of the
      procollagens and MMP-2 was not significantly altered, while ulcer diameter was
      significantly reduced. We conclude that the early onset and long duration of
      collagens' expression points to their central structural and functional role in
      gastric ulcer healing. MMP-2 seems to be involved in both active ulceration and
      ECM remodeling. The timing of TIMP/MMP expression may be critical for proper
      restoration of gastric wall integrity.

PMID- 11525258
TI  - Low prevalence of latently Epstein-Barr virus-infected cells in chronic
      gastritis.
AB  - The association of Epstein-Barr virus (EBV) with a proportion of gastric
      carcinomas is well established. The role of EBV in conditions predisposing to
      carcinoma such as chronic gastritis has remained undefined, however. We used in
      situ hybridization with radioactive and nonradioactive single-stranded RNA probes
      specific for the EBV small latent nuclear transcripts, EBER1 and EBER2, to
      analyze biopsy specimens from 242 patients with mild to severe chronic gastritis
      of Sydney classification types A, B, and C. A small number of EBV infected
      lymphocytes was detected in only nine cases, even in biopsies investigated with
      radioactive probes. Labeling of epithelial or stromal cells was not observed. The
      paucity of latently EBV-infected cells in chronic gastritis biopsies differs from
      the previously reported higher prevalence of virus carrying cells in inflammatory
      conditions at other sites of the gastrointestinal tract. These findings argue
      against a direct involvement of EBV in the pathogenesis of chronic gastritis. The
      low prevalence of EBV-positive cells suggests that local factors do not favor the
      entry and retention of circulating EBV-infected lymphocytes in gastric mucosa.
      Moreover, our findings indicate that EBV infection of gastric epithelial cells is
      not an early event in gastric carcinogenesis.

PMID- 11525260
TI  - Immune response to autologous and heterologous Helicobacter pylori antigens in
      humans.
AB  - Infection of humans with Helicobacter pylori results in the development of
      chronic gastritis and plays an important role in gastric ulcer pathogenesis.
      Despite the infiltration of the mucosa with specific immunocompetent cells and
      production of specific antibodies, the infection usually persists for life. This
      study was performed to investigate if immunologic mechanisms exist which could
      contribute to the inability of the host to terminate the infection. Therefore, we
      compared the in vitro immunoreactivity of peripheral blood mononuclear cells
      (PBMC) from H. pylori-infected patients after stimulation with sonicated H.
      pylori bacteria from the stomach of the patient (autologous bacterial strain)
      with stimulation by bacteria from other patients (heterologous bacteria). We
      measured cell proliferation, expression of T cell activation markers CD25, HLA
      DR, and CD71, as well as production ofinterleukin-10 (IL-10), an inhibitory
      cytokine. We found that the proliferative response of PBMC was significantly
      lower after autologous than after heterologous stimulation. Furthermore,
      secretion of IL-10 in the culture supernatants was significantly higher when PBMC
      were incubated with autologous than with heterologous H. pylori antigens. No
      significant differences between autologous or heterologous stimulation were
      observed in the increased expression of T cell activation markers. These data
      indicate that systemic immunologic response to H. pylori are strain-dependent.
      For further studies of the immune responses towards H. pylori, the use of an
      autologous stimulatory system seems necessary.

PMID- 11525259
TI  - Are lymphocytic monoclonality and immunoglobulin heavy chain (IgH) rearrangement
      premalignant conditions in chronic gastritis?
AB  - Normal gastric mucosa is devoid of lymphoid cells. Any increase of lymphocytes
      suggests chronic inflammation. Infection with Helicobacter pylori (Hp) is the
      major cause for nonautoimmune chronic gastritis and induces a mixed cellular
      response resulting in an acquired lymphoid tissue, or MALT (mucosa-associated
      lymphoid tissue). Hp has also been implicated in the genesis of gastric MALT
      lymphoma. Polymerase chain reaction-based assays to detect the expansion of
      monoclonal B-cells have also been used to corroborate the diagnosis. In a
      considerable number of cases monoclonal B-cells remain detectable in follow-up
      biopsies, with the lymphoma being in complete histological remission. The
      clinical relevance of this finding is not clear yet. However, there also exist
      different reports that monoclonal B-cells can be found in gastric biopsies of
      patients with neither a histological sign nor a present or past history of
      lymphoma. In the light of these findings we address the question whether B-cell
      monoclonality can be seen as a premalignant condition in chronic gastritis and
      conclude that as of now the relevance of the finding of B-cell monoclonality
      remains unclear. As of now the only and gold standard for the diagnosis of
      gastric MALT-lymphoma is histopathology.

PMID- 11525261
TI  - Confocal microscopy and stereology: estimating volume, number, surface area and
      length by virtual test probes applied to three-dimensional images.
AB  - The opportunities of confocal microscopy applied to morphometry of microscopical
      structures are presented and demonstrated on stereological methods based on
      evaluation of optical sections within a thick slice and using computer-generated
      virtual test probes. Such methods, allowing arbitrary orientation of the thick
      slice, can be used for estimating volume, number, surface area, and length. The
      methods using spatial grid of points, disector, fakir, and slicer probes are
      described and illustrated by different examples using our freeware 3DTOOLS
      software and their variance and applicability are discussed. It is shown that
      shifted triple or quadruple spatial grids of lines are very efficient for the
      surface area and volume estimation by the fakir method.

PMID- 11525262
TI  - The European Thyroid Association meets in Warsaw.

PMID- 11525263
TI  - Topical triiodothyronine stimulates epidermal proliferation, dermal thickening,
      and hair growth in mice and rats.
AB  - The skin is a classic target tissue for thyroid hormone action. Although the
      histology of skin in hypothyroid states is well documented, the literature
      contains little assessment of skin in thyrotoxic states. In light of the paucity
      of information on skin under the influence of excess thyroid hormone, we
      investigated the direct effect of thyroid hormone on skin. Triiodothyronine (T3)
      was applied topically daily in liposomes to SKH-1 hairless mice for 7 days and to
      CD rats for 2 weeks. There was a dose-dependent increase in epidermal
      proliferation, dermal thickening, and hair growth in T3-treated animals. Mice
      that received 3.8 microg of T3 had 42% more hairs per millimeter than controls (p
      < 0.01), hair length that was 1,180% longer (p < 0.001), 49% greater epidermal 3H
      thymidine incorporation (p < 0.01), and 80% more 5-bromo-2'-deoxyuridine (BrdU)
      stained cells (p < 0.05). Rats receiving 12.8 microg T3 had 48% greater dermal
      thickness than controls (p < 0.001), 26% greater epidermal thickness (p < 0.001),
      85% more hairs per millimeter (p < 0.005), and 130% greater 3H-thymidine
      incorporation into the epidermis (p < 0.01). Thus, topically applied thyroid
      hormone has dramatic effects on both skin and hair growth. These observations
      offer a new strategy for developing thyroid hormone and its analogues for
      treating disorders of skin and hair growth.

PMID- 11525264
TI  - Susceptibility of thyroid cancer cells to 7-hydroxystaurosporine-induced
      apoptosis correlates with Bcl-2 protein level.
AB  - 7-Hydroxystaurosporine (UCN-01) is a selective protein kinase C (PKC) inhibitor
      and is being developed as a novel anticancer agent. Because of reports that PKC
      may be involved in the pathogenesis of some forms of thyroid cancers, we examined
      four thyroid carcinoma lines (FRO, KAT5, NPA, and WRO). These cells were found to
      have different susceptibility to UCN-01 treatment, and there appeared to be a
      correlation between UCN-01-induced death and expression levels of endogenous Bcl
      2. KAT5 cells, which normally express a low amount of Bcl-2, exhibited
      significantly higher sensitivity to UCN-01-induced death than the other cell
      lines. Of interest, susceptibility did not relate to PKC activity or its
      inhibition by UCN-01. In order to investigate the role of Bcl-2 in UCN-01-induced
      death, KAT5 cells were transfected to overexpress Bcl-2. KAT5/Bcl-2 cells were
      capable of conferring resistance to UCN-01-induced death. Furthermore,
      upregulating of Bcl-2 by 1alpha,25-dihydroxyvitamin D3 (VD3) could protect
      primary thyroid cell from death induced by UCN-01. Both in situ TUNEL staining
      and the flow cytometric analysis of cytokeratin-18 (CK18) cleavage confirmed that
      UCN-01 was indeed inducing apoptosis, and that this effect was inhibited by
      increased expression of Bcl-2. These results suggest that the Bcl-2 can block the
      UCN-01-activated cell death pathway and that the expression of Bcl-2 is inversely
      related to thyroid carcinoma cell susceptibility to UCN-01. Therefore, the
      analysis of the expression of apoptosis suppressors provides a basis for the use
      of UCN-01 in the treatment of thyroid cancer.

PMID- 11525265
TI  - A radioimmunoassay for type I iodothyronine 5'-monodeiodinase in human tissues.
AB  - We have developed a sensitive, specific and reproducible radioimmunoassay (RIA)
      for measurement of human type I monodeiodinase (5'-DI) protein. Anti-5'-DI
      antibody was produced by immunization of rabbits with a conjugate of bovine serum
      albumin and a 16 amino acid synthetic peptide, corresponding to a portion of the
      carboxy-terminal region of the human 5'-DI (PI-99). In a final dilution of 1:500,
      our anti-5'-DI antibody bound about 30%-35% of a tracer amount of 125I-PI-99. The
      detection threshold of the RIA approximated 0.4 pmol PI-99 or an equivalent
      amount of 0.4 pmol 5'-DI. The coefficient of variation averaged 5% within an
      assay and 14% between assays. Dose-response curves of tissue proteins were
      essentially parallel to that of PI-99. In a total number of 35 normal human
      tissue samples, the mean (+/- standard deviation [SD], picomole per milligram of
      protein [pmol]) 5'-DI content was 25 +/- 6.7 in kidney, it was significantly
      lower (p < 0.05) in liver at 3.9 +/- 1.1, 2.8 +/- 0.8 in intestine, 2.3 +/- 0.98
      in adrenal, 4.2 +/- 2.5 in skeletal muscle, 3.8 +/- 1.4 in heart and 2.6 +/- 2.4
      in thyroid; it was 1.4 +/- 0.3 in Graves' thyroid. Our data suggest that (1) 5'
      DI is distributed widely among human tissues; (2) kidney is the tissue most
      enriched with 5'-DI; (3) 5'-DI content in the thyroid is not increased in Graves'
      disease.

PMID- 11525266
TI  - Loss of heterozygocity at the thyroid peroxidase gene locus in solitary cold
      thyroid nodules.
AB  - Germline mutations in both alleles of the thyroid peroxidase (TPO) gene have been
      reported as a frequent cause of congenital hypothyroidism resulting from a total
      iodide organification defect (TIOD). Because TPO mutations have a prevalence of 1
      in 66,000 newborns and is inherited in an autosomal recessive mode the frequency
      of a heterozygous germline mutation in the TPO gene should reach about 1 in 260
      in the population. A somatic TPO mutation coinciding with a somatic loss of one
      of the TPO alleles or a TPO germline mutation could lead to somatic loss of TPO
      activity with impairment of thyroid hormone synthesis and decrease of growth
      control. The latter would lead to increased thyroid epithelial cell proliferation
      and the subsequent development of a scintigraphically cold thyroid nodule (CTN).
      To test this hypothesis we studied 40 CTN for the presence of mutations or loss
      of heterozygosity (LOH) in the TPO gene. For comparisons we also studied LOH in
      17 autonomously functioning thyroid nodules (AFTN). Genomic DNA was extracted
      from nodular and surrounding tissue, polymerase chain reaction (PCR) amplified,
      sequenced, and analyzed for LOH. In 6 CTNs of 37 informative cases we detected
      LOH using the genomic markers sRA, D2S2268, and D2S319 within or near the TPO
      gene locus (2p24-25). In contrast, a genomic marker closer to the centromer
      (D2S144, 2p24-21) shows LOH in only 1 CTN. We did not detect LOH in AFTN. In none
      of the cases a germline or somatic mutation in the TPO gene was detectable in the
      TPO gene. LOH in 6 of 37 CTNs suggests that genetic defects at the TPO or the
      chromosomal locus 2p24-25 might play a role in the etiology of CTNs. However, we
      did not find the combination of LOH with a somatic mutation in the TPO gene. It
      is therefore likely that a gene defect near the TPO locus is part of the
      neoplastic process in a subgroup of CTNs.

PMID- 11525267
TI  - Reevaluation of the impact of a stringent low-iodine diet on ablation rates in
      radioiodine treatment of thyroid carcinoma.
AB  - Prior analyses of the impact of stringent, preablative low-iodine diets (LIDs) on
      ablation in patients with differentiated thyroid cancer postthyroidectomy are
      dated. We retrospectively reviewed first-time, short-term ablation rates for 44
      LID patients and 50 patients following a regular diet (RD) who were verbally
      instructed to avoid salt, seafood, and multivitamins containing iodine. Patients
      who had undergone ablation were given between 100 and 200 mCi of 131I, depending
      on the presence of metastases. We found a 68.2% ablation rate for LID patients,
      compared to a 62.0% rate for RD patients, a nonsignificant difference (p = 0.53).
      We observed a dose-response relationship for both patient groups, with higher
      ablation rates corresponding to higher doses of radioiodine administered. We also
      measured iodine levels in spot urine samples from 7 matched LID patients and 7
      matched RD adherents (healthy volunteers) prediet and postdiet as well as 39
      healthy volunteers. LID patients had a lower mean urinary iodine level postdiet
      (173.9 microg/L; range, 45-1,217 microg/L; standard deviation [SD] = 127.7) than
      the RD patients (mean, 381.4 microg/L; range, 140-630 microg/L; SD = 196.3) or
      the 39 normal controls (444.0 microg/L; range, 50-1,690 microg/L; SD = 413.4).
      Whereas the LID lowered urinary iodine levels by 69.4% from prediet values, the
      RD reduced urinary iodine by 23.6%. Although differences in the reduction of
      urinary iodine levels between the LID and the RD were substantial, both groups
      experienced equivalent outcomes. The level of iodine in the American diet has
      progressively decreased, and may be much lower now than when prior LID studies
      were conducted. We suggest that prescribing a refined, less stringent diet that
      avoids high-iodine-containing foods would offer equivalent outcomes with
      increased patient convenience.

PMID- 11525268
TI  - Management practices among primary care physicians and thyroid specialists in the
      care of hypothyroid patients.
AB  - Prospective studies are not available to address various issues commonly
      encountered in the management of hypothyroid patients. We have conducted a case
      based mail survey of American Thyroid Association (ATA) members and primary care
      providers (PCP) regarding hypothyroidism management issues. A majority of ATA
      members and a minority of PCPs used antithyroid antibody testing in the
      evaluation of hypothyroidism. Approximately 2/3 of all respondents indicated that
      they would treat patients with mild thyroid failure when antithyroid antibodies
      are negative; 77% of PCPs and 95% of ATA members recommended treatment when
      antibodies are positive. For a young patient with mild thyroid failure, 71% of
      ATA members would initiate a full levothyroxine (LT4) replacement dose of 1.6
      microg/kg per day or slightly lower; PCPs were more likely to start with a low
      dose and titrate upwards. For a young patient with overt hypothyroidism, 42% of
      PCPs and 51% of ATA respondents recommended an initial full LT4 replacement dose.
      The majority of all respondents would start with a low LT4 dose and adjust the
      dose gradually in an elderly patient, regardless of the severity of thyroid
      hormone deficiency. More than 40% of ATA respondents chose a target thyrotropin
      (TSH) range of 0.5-2.0 microU/mL for a young patient while 39% favored a goal of
      1.0-4.0 microU/mL for an elderly patient. PCPs more often chose a broader TSH
      goal of 0.5-5.0 microU/mL. In conclusion, the current practice patterns of PCPs
      and ATA members that were elicited in this survey differ significantly in regard
      to the evaluation and management of hypothyroidism.

PMID- 11525269
TI  - Effects of thyroid hormone deficiency on electrocardiogram findings of
      congenitally hypothyroid neonates.
AB  - Hypothyroid status is believed to cause various metabolic changes in infants.
      However, it is interesting that even severely hypothyroid neonates, detected
      during mass neonatal screening, rarely show bradycardia, hypothermia, or
      inactivity. To study cardiac functions of screen-detected neonates with
      congenital hypothyroidism (CH), we recorded the electrocardiograms (ECG) of 53
      screen-detected CH neonates before levothyroxine (LT4) replacement therapy, and
      15 age-matched normal neonates for controls. The 53 CH neonates were divided into
      two groups according to initial serum thyroid hormone levels: a mildly
      hypothyroid group (n = 37), serum thyroid-stimulating hormone (TSH) less than 100
      microIU/mL and free thyroxine (FT4) 0.6 ng/dl or more; and a severely hypothyroid
      group (n = 16), TSH 100 microIU/mL or more and FT4 less than 0.6 ng/dL. TSH, FT4,
      and other blood chemicals were measured on an autoanalyzer (Hitachi 7170). After
      blood sampling, the ECG was recorded during induced sleep by oral administration
      of triclofos sodium syrup. ECG parameters, including HR, PR, QRS, QT time and
      corrected QT time (QTc) were automatically obtained, using an auto-ECG analyzing
      system. The following results were obtained. No CH patients showed abnormal ECG
      findings. There was no significant difference of the mean heart rates (HRs)
      between the mildly hypothyroid (147.5 +/- 16.3 beats per minute) and the control
      group (148.3 +/- 12.1 beats per minute). The mean HR in the severely hypothyroid
      group (134.0 +/- 17.9 beats per minute, p = 0.007) was significantly low compared
      with the normal control group. However, all values were within normal ranges. QTc
      in the severely hypothyroid group (0.414 +/- 0.015, p = 0.033) was significantly
      shorter than in the control group (0.440 +/- 0.052). No statistical differences
      of PR, QRS, and QT time were noted among the three groups. All ECG parameters
      were within normal ranges. HR positively correlated with FT4 and log (FT4), and
      negatively with TSH and log (TSH). From these results we conclude that the
      deficiency of thyroid hormones does not affect ECG findings of congenitally
      hypothyroid neonates. This may be consistent with the unexpectedly mild signs and
      symptoms of screen-detected hypothyroid neonates.

PMID- 11525270
TI  - Validity of self-reported hyperthyroidism and hypothyroidism: comparison of self
      reported questionnaire data with medical record review.
AB  - Studies that aim at identifying genes or environmental factors contributing to
      the development of autoimmune thyroid disease (AITD) demand that several hundred
      patients and control subjects be assessed. In these large studies, the laboratory
      methodology is often described in detail whereas little attention is given to an
      accurate description of the study population. Usually, a diagnosis of AITD in the
      control group is based on self-reported disease status. Although such studies
      have been criticized for diagnostic inaccuracy, no study has evaluated the
      validity of self-reported hyperthyroidism and hypothyroidism in detail. We have
      assessed the validity of self-reported hyperthyroidism and hypothyroidism in 401
      twin pairs from among 6,628 same gender pairs, ages 18-41 years who participated
      in a nationwide questionnaire survey in 1994. The self-reported questionnaire
      data were compared with information from medical records and the 1/kappa
      coefficient, sensitivity, and specificity were determined. Overall, there was
      only a slight to fair agreement between the self-reported questionnaire data and
      medical record data as shown by kappa values of 0.18, 0.21, and 0.26 for
      hyperthyroidism and hypothyroidism as a group, hyperthyroidism and
      hypothyroidism, respectively. For both hyperthyroidism and hypothyroidism, the
      sensitivity of the self-reported diagnosis was 0.98, whereas the specificity was
      0.57 and 0.67 for self-reported hyperthyroidism and hypothyroidism, respectively.
      In conclusion, the validity of self-reported hyperthyroidism and hypothyroidism
      is unsatisfactorily low. However, by combining self-reports with valid
      retrospective data on diagnostic findings it can be used as a sampling method in
      large epidemiological or genetic studies.

PMID- 11525271
TI  - Long-term follow-up of patients with initially benign thyroid fine-needle
      aspirations.
AB  - Fine-needle aspiration (FNA) is currently the most reliable diagnostic means in
      the clinical work-up of thyroid nodules. However, most of the available data on
      the diagnostic reliability of thyroid FNA derives from biopsies done just before
      surgery or from short-term observations, whereas data on the long-term
      reliability of benign FNA results, is extremely limited. Over the 17-year period
      between 1979 and 1996, thyroid FNA performed on 849 patients in our endocrine
      clinic. An initially benign result was reported in 578 patients for a total of
      631 nodules. Mean follow-up period was 8.1 +/- 4.4 years (+/-standard deviation
      [SD]; median, 6.9 years). In order to ensure the completeness of our follow-up
      data, we supplemented our own patients' data with data from the Israel Cancer
      Registry for documentation of thyroid malignancy. Sixty-six of the patients with
      an initially benign FNA diagnosis were rebiopsied during follow-up. Five patients
      (0.85%) of all those with an initial benign FNA diagnosis, were subsequently
      found to have thyroid malignancy diagnosed 6 months or more after the initial
      evaluation. Three of the newly diagnosed malignancies were follicular and two
      were papillary carcinomas. Three of the patients had elements of being at high
      risk: previous head irradiation, previous thyroid surgery with an occult cancer,
      and a growing goiter, respectively. Only 1 of 35 patients who had more than one
      benign FNA results was subsequently diagnosed with thyroid malignancy (follicular
      carcinoma). These results indicate that the rate of subsequent thyroid
      malignancies in patients with an initial benign FNA diagnosis is low, and thus
      benign thyroid FNA results provide a high level of long-term assurance. Still,
      repeating FNA is warranted in patients with longstanding thyroid nodules,
      particularly if at increased risk for cancer, or if a goiter is found to have
      changed its morphological characteristics over time.

PMID- 11525272
TI  - Lack of substantial effects of raloxifene on thyroxine-binding globulin in
      postmenopausal women: dependency on thyroid status.
AB  - Long-term estrogen therapy can modify thyroid hormone kinetics by increasing
      serum concentration of thyroxine-binding globulin (TBG). Raloxifene is a recently
      developed selective estrogen receptor modulator (SERM) for the treatment of
      osteoporosis, which possesses estrogenic and antiestrogenic properties. In a
      prospective and randomized study, we investigated the effects of raloxifene on
      TBG levels and on the serum concentrations of free thyroxine (FT4), thyroxine
      (T4), triiodothyronine (T3), and thyrotropin (TSH) in controls and in patients
      receiving TSH-suppressive doses of levothyroxine (LT4). Twenty-nine
      postmenopausal osteopenic (n = 14) and osteoporotic (n = 15) women were
      investigated over a period of 6 months. Group 1 (n = 15) included control
      patients and group 2 (n = 14) patients receiving TSH-suppressive dose of LT4. All
      patients were treated with raloxifene hydrochloride, 60 mg/d, for a period of 6
      months. Serum basal TBG values were found higher in Group 1 compared to Group 2
      (26.2 2 microg/mL vs. 21.4 2.1 microg/ml; p < 0.01). The TBG levels raised
      slightly in group 1 from 26.2 2 microg/mL to 28.6 3.1 microg/mL; p < 0.05 (in
      group 2 from 21.4 2.1 microg/mL to 22.2 2.3 microg/mL, not significant) after 3
      months of treatment and failed to show any further significant change until the
      end of the study. Serum concentrations of T4, FT4, T3, and TSH levels changed
      insignificantly in both groups up to the completion of the study. Moreover,
      patients remained clinically euthyroid. Our findings may provide evidence that
      TBG levels, and consequently, thyroid function are not substantially affected by
      treatment with raloxifene. Additionally, TBG levels may also be influenced by
      small variations of thyroid function as subclinical hyperthyroidism.

PMID- 11525273
TI  - Immunostaining for Met/HGF receptor may be useful to identify malignancies in
      thyroid lesions classified suspicious at fine-needle aspiration biopsy.
AB  - The receptor for hepatocyte growth factor (Met) is not expressed in the normal
      thyroid but it is overexpressed in most thyroid carcinomas. We evaluated whether
      Met immunostaining of cytological smears from fine-needle aspiration biopsy
      (FNAB) may be useful for the preoperative diagnosis of thyroid cancer. Notably,
      routine cytological examination often fails to distinguish well-differentiated
      follicular carcinomas and a proportion of papillary carcinomas (low-grade
      papillary carcinomas and papillary carcinomas follicular variant [FVPTC]) from
      benign lesions: all these lesions are usually classified as suspicious. We
      examined 80 thyroid lesions diagnosed as suspicious at cytology that had
      subsequently undergone surgery. The histologic diagnosis had been: papillary
      carcinomas (n = 14), FVPTC (n = 11), follicular carcinomas (n = 25), atypical
      follicular adenomas (n = 5), follicular adenomas (n = 20), and nodular goiters (n
      = 5). We also studied typical papillary carcinomas (n = 30) and nodular goiters
      (n = 10), all correctly diagnosed at cytology. In lesions classified suspicious
      at routine cytology, Met immunostaining was positive in 12 of 14 (85.7%)
      papillary carcinomas, 8 of 11 (72.7%) FVPTC, 7 of 25 (28%) follicular carcinomas,
      and 5 of 5 atypical adenomas. In contrast, none of the 25 lesions cytologically
      suspicious but benign at histology were positive. These data suggest that Met
      immunostaining of suspicious cytological smears are useful for identifying
      malignant lesions, especially those with a papillary histotype.

PMID- 11525274
TI  - Monoallelic deletion in the 5' region of the thyroglobulin gene as a cause of
      sporadic nonendemic simple goiter.
AB  - The cause of sporadic simple goiter is unknown in most cases. Family studies have
      suggested that this disorder may have a genetic component in some patients. We
      have previously demonstrated that some cases of endemic and nonendemic simple
      goiter are associated with a mutation within exon 10 of the thyroglobulin gene.
      Here we report a study of 50 cases diagnosed as having nonendemic simple goiter,
      and found 1 case with a large heterozygous deletion within the thyroglobulin
      gene. The deletion involves the promoter region and the 11 first exons of this
      gene and is associated with a euthyroid state. We hypothesize that the absence of
      thyroglobulin synthesis from the deleted allele may be responsible for a
      decreased level of thyroglobulin mRNA. Euthyroidism would be achieved by
      thyrotropin (TSH) stimulation but at the expense of goiter development.

PMID- 11525275
TI  - Renal metastases from thyroid papillary carcinoma: study of sodium iodide
      symporter expression.
AB  - Kidney metastases from thyroid cancer are rare. We report two such patients and
      demonstrate that the in vivo 131I uptake by the kidney metastasis is associated
      with high levels of sodium iodide (Na+/I-) symporter (NIS) expression in the
      first case. Case 1: A 61-year-old woman with papillary thyroid carcinoma
      follicular variant (PTC-FV) presented with scapular metastasis. After
      thyroidectomy and scapulectomy, a 131I posttherapy scan showed left upper
      quadrant uptake. A 3.0-cm metastatic PTC-FV deposit was removed by partial
      nephrectomy. Case 2: A 53-year-old woman presented with back pain. A computed
      tomography (CT) scan showed a 3.5-cm renal mass, a multinodular goiter, and lung
      metastases thought secondary to a renal cell carcinoma. A unilateral nephrectomy
      revealed metastatic PTC-FV. After thyroidectomy, a 131I posttherapy scan showed
      lung and skeletal metastases. NIS immunoreactivity in tumoral tissue was strongly
      positive in the primary tumor, shoulder, and kidney metastasis in case 1, as well
      as in the primary tumor in case 2. Spotty, low-level NIS expression was observed
      in the kidney metastasis in case 2. In conclusion, kidney metastases of PTC-FV
      may occasionally retain adequate levels of NIS expression, enabling their
      detection during life. Thus, intense uptake in the abdomen during 131I imaging
      should not be assumed to be physiological gastrointestinal tract residual
      radionuclide activity.

PMID- 11525276
TI  - Images in thyroidology. A man with a 99mTc-pertechnetate-enhancing mediastinal
      mass.

PMID- 11525277
TI  - Thoughts on the role of iodine in the emergence of modern humans.

PMID- 11525278
TI  - Still worrying with trace chemical pollution.

PMID- 11525279
TI  - A reassessment of trace metal budgets in the Western Mediterranean Sea.
AB  - This paper presents inputs and output fluxes of dissolved metals (As, Cd, Co, Cu,
      Fe, Mn, Ni, Pb and Zn) into and out the Western Mediterranean. These flux
      estimates are based on the most recently published concentrations and fluxes for
      the atmosphere, the rivers and the straits. Comparison of the different sources
      shows the predominance of the inputs through the straits over other sources. The
      river input is smaller than the atmospheric input except for As. For all elements
      except Fe, output flux and input flux are balanced; iron budget indicates
      transfer from the dissolved to the particulate phase.

PMID- 11525280
TI  - Deposition of semi-volatile organochlorine compounds in the free troposphere of
      the eastern North Atlantic Ocean.
AB  - Deposition samples were taken at a height of 2367 m above sea level (m.a.s.l.) on
      the Island of Tenerife from May 1999 until July 2000 and analysed for 19
      polychlorinated biphenyl (PCB) congeners, hexachlorobenzene (HCB),
      hexachlorocyclohexanes (HCH) and DDTs. This site is located above the inversion
      layer, so samples represent background concentrations of the free troposphere.
      The average deposition fluxes of HCB, total HCH, DDTs and PCBs were 86, 400, 110
      and 780 ng m(-2) yr(-1), respectively, being lower than those reported at sea
      level in continental or marine areas. All compounds are generally found in higher
      abundance in the wet precipitation samples. However, these samples only represent
      a fraction, e.g. 33%, of the total deposition load. Annual mass balance
      calculations show that wet precipitation is essentially responsible for the
      deposition of the low molecular weight OC whereas dry deposition accounts for
      more than 50% of the higher molecular weight PCBs.

PMID- 11525281
TI  - Marine risk assessment: linear alkylbenzenesulponates (LAS) in the North Sea.
AB  - The fate of linear alkylbenzenesulponates (LAS) in estuaries and coastal areas of
      the North Sea has been characterized with simple environmental models. The
      predicted concentration range in the estuaries around the North Sea (0.9-9 microg
      LAS l(-1)) was validated by monitoring data (1-9 microg LAS l(-1)). In offshore
      sites of the North Sea, it is estimated--and experimentally verified for a few
      sites--that the LAS concentration is below analytical detection limit (i.e., 0.5
      microg LAS l(-1)). The effects of LAS on marine organisms have been reviewed. For
      short-term acute tests, there was no significant difference (p = 0.83) between
      the mean LC50 values of freshwater and marine organisms (mainly pelagic species
      tested, 4.1 and 4.3 mg LAS l(-1), respectively). For longer-term chronic tests,
      it appeared that the sensitivity (mean no-observed effect concentration (NOEC)
      value) of marine and freshwater organisms (0.3 and 2.3 mg LAS l(-1),
      respectively) was significantly different pt-test = 0.007). The predicted no
      effect-concentrations (PNEC) were 360 and 31 microg LAS l(-1), for freshwater and
      marine pelagic communities, respectively. Given that the maximum expected
      estuarine and marine concentrations are 3 to > 30 times lower than the PNEC, the
      risk of LAS to pelagic organisms in these environments is judged to be low.

PMID- 11525282
TI  - Cellular and molecular responses to endocrine-modulators and the impact on fish
      reproduction.
AB  - Anthropogenic chemicals in the aquatic environment are known to cause
      reproductive disturbances in vertebrate and invertebrate organisms, by
      interfering with the endocrine systems. Laboratory-based in vivo and in vitro
      studies have indicated that several of the anthropogenic and other naturally
      occurring chemicals in the environment can cause adverse reproductive effects.
      Various definite or possible reproductive abnormalities caused by endocrine
      disruption have been identified, but in majority of the reported cases, it is not
      known whether adverse effects have occurred in the population level of biological
      organization. Disruption of the hormonal functions in fish may have effects on a
      number of events, including sexual maturation, gamete production and transport,
      sexual behaviour, fertility, gestation, lactation or modifications in other
      functions that are dependent on the integrity of the reproductive system.
      Although several reproductive effects have been reported, but the degree of
      causality established between the abnormalities observed and exposure to
      particular chemicals is variable, and understanding of the mechanism(s) is
      limited. Fishes are a vital source of proteins and lipids for humans and domestic
      animals, forming the basis for economically important fisheries and aquaculture.
      Large efforts have recently been denoted to dissect the mechanisms of action of
      xenobiotics in aquatic species, with the ultimate aim of detecting, controlling
      and possibly intervening in chemical exposure and its effects on the aquatic
      ecosystem and humans. In this context, we ought to be concerned with the health
      and safety of aquatic species per se, as well as a resource for human needs.

PMID- 11525283
TI  - Contaminant-stimulated reactive oxygen species production and oxidative damage in
      aquatic organisms.

PMID- 11525284
TI  - Effects of PCBs on reactive oxygen species (ROS) production by the immune cells
      of Paracentrotus lividus (Echinodermata).
AB  - The impact of four PCB congeners: 3,3',4,4'-tetrachlorobiphenyl (IUPAC congener
      #77), 3,3',4,4',5-pentachlorobiphenyl (IUPAC #126), 2,2',4,4',5,5'
      hexachlorobiphenyl (IUPAC #153) and 3,3',4,4',5,5'-hexachlorobiphenyl (IUPAC
      #169) was investigated on the reactive oxygen species (ROS) production by
      coelomocytes of the echinoid Paracentrotus lividus, an important species in
      marine benthic ecosystems. PCBs were found to increase ROS production and to
      delay the time of peak production. These effects were stronger on bacteria
      stimulated cells and were congener-specific: coplanar congeners (#77, 126 and
      169) had more effect than the non-coplanar PCB #153. Among coplanar congeners,
      PCB #169 showed dose-dependent effects whereas PCB #77 and 126 were more toxic at
      high and low doses, respectively. The relative immunotoxicity of the different
      PCB congeners is discussed in the light of their structural properties and
      biological affinities.

PMID- 11525285
TI  - Antifouling paint booster biocides in the UK coastal environment and potential
      risks of biological effects.
AB  - In the yachting sector of the UK antifouling market, organic biocides are
      commonly added to antifouling preparations to boost performance. Few data
      presently exist for concentrations of these compounds in UK waters. In this study
      the concentrations of tributyltin (TBT) and eight booster biocides were measured
      before and during the 1998 yachting season. The Crouch Estuary, Essex, Sutton
      Harbour, Plymouth and Southampton Water were chosen as representative study sites
      for comparison with previous surveys of TBT concentrations. Diuron and Irgarol
      1051 were the only organic booster biocides found at concentrations above the
      limits of detection. Diuron was measured at the highest concentrations, whilst
      detectable concentrations of both Irgarol 1051 and diuron were determined in
      areas of high yachting activity (e.g. mooring areas and marinas). Maximum
      measured values were 1,421 and 6,740 ng/l, respectively. Lower concentrations of
      both compounds were found in open estuarine areas, although non-antifouling
      contributions of diuron may contribute to the overall inputs to estuarine
      systems. TBT was found to be below or near the environmental quality standard
      (EQS) of 2 ng/l for all samples collected from estuarine areas frequented by
      pleasure craft alone, but with much higher concentrations measured in some
      marinas, harbours and in areas frequented by large commercial vessels. Using the
      limited published environmental fate and toxicity data available for antifouling
      booster biocides, a comparative assessment to evaluate the risk posed by these
      compounds to the aquatic environment is described. TBT still exceeds risk
      quotients by the greatest margins, but widespread effects due to Irgarol 1051 and
      less so diuron cannot be ruled out (particularly if use patterns change) and more
      information is required to provide a robust risk assessment.

PMID- 11525286
TI  - The effect of TBT on the structure of a marine sediment comunity--a Boxcosm
      study.
AB  - The effect of tri-n-butyl tin (TBT) on an intact marine sediment community after
      five months exposure was investigated. Changes in the structure of macro- and
      meiofauna communities were determined, as well as the functional diversity of the
      microbial community using BIOLOG microplates for Gram negative bacteria.
      Development of tolerance in the microbial community was investigated using
      Pollution Induced Community Tolerance (PICT) experiments with fluxes of nutrients
      as effect indicators. TBT affected the structure and recruitment of the macro-
      and meiofauna at nominal additions of 30-137 micromol TBT/m2 sediment. Number of
      species, diversity, biomass and community similarity was reduced at these
      concentrations compared to control. Species that molt seemed to be the most
      tolerant since they were predominant in boxes that had received the highest TBT
      addition and echinoderms were the most sensitive species. Renewed addition of TBT
      in PICT experiments with sediment from each boxcosm showed that TBT had an effect
      on individual nutrient fluxes from all sediments. Analyses of the flux patterns
      revealed a memory of previous TBT exposure, either due to induced tolerance or
      other community conditioning.

PMID- 11525287
TI  - An assessment of the potential use of the nematode to copepod ratio in the
      monitoring of metals pollution. The Chanaral case.
AB  - We discuss the use of the nematode to copepod ratio in relation to determining
      the extent of metals impact using the Chanaral area of northern Chile, where the
      dumping of copper mine tailings has taken place for many years, as an example.
      Data were collected from 12 beaches in the area on eight occasions between
      January 1997 and October 1998. We find that the ratio is not a good predictor of
      pollution due to the generally low densities of meiofauna on impacted beaches and
      the absence of harpacticoid copepods from those beaches. We suggest that in the
      case of metal pollution the mean number of Harpacticoida per site may be a better
      indicator of impact stress. We rule out the use of the nematode to copepod ratio
      as an indicator in biomonitoring studies where metal enrichment is thought to
      occur.

PMID- 11525288
TI  - Prostate pathology: histologic and molecular perspectives.
AB  - The field of prostate cancer research is poised for dramatic improvements in our
      ability to better diagnose men at risk of prostate cancer and to better predict
      prognosis and response to treatment. Histopathologic and molecular analyses lie
      at the heart of these issues. Improvements in our understanding of the mechanisms
      of prostate carcinogenesis and in determining why the prostate seems to be so
      highly targeted for cancer development will lead to rational strategies of
      disease prevention.

PMID- 11525289
TI  - Radiation therapy for the treatment of locally advanced and metastatic prostate
      cancer.
AB  - Radiation therapy for locally advanced PCa continues to evolve. A current
      treatment recommendation for nonmetastatic, high-risk disease includes AS
      combined with RT. The precise duration and sequencing of AS has not been
      established but most frequently includes treatment in the neoadjuvant,
      concomitant and, occasionally, adjuvant periods. As technology allows higher
      doses without significant increases in morbidity and as clinical data provide
      proof of a radiation dose response, RT doses continue to escalate. The goal of
      therapy for metastatic disease continues to focus on the relief of pain and the
      improvement in quality of life. Multiple studies document the significant role RT
      plays in achieving these goals. Focal RT and systemic radioisotopes have become
      the mainstay of management in this patient group and the development of newer
      isotopes that cause less marrow toxicity will improve the therapeutic ratio and
      provide an opportunity for their use with systemic chemotherapy. As molecular and
      genomic technologies advance, directed targeting of critical cellular radiation
      response pathways hold the promise of improved radiation response and
      individualized, tailored therapy.

PMID- 11525291
TI  - Nonandrogenic mediators of prostatic growth.
AB  - Prostate growth and development are primarily under the control of androgens;
      however, other factors can also influence prostatic growth through alternative
      pathways. This article discusses some of the major nonandrogenic mediators of
      prostate growth. Information on the pathways by which these factors exert their
      effects is also reviewed.

PMID- 11525290
TI  - Prevention of prostate cancer.
AB  - Strategies for reducing the occurrence of prostate cancers will be critical in
      limiting the morbidity and mortality of this disease. The long latency period of
      prostate tumors and improved understanding of prostate carcinogenesis suggest
      opportunities for effective preventive measures. Because androgen is integral to
      prostatic carcinogenesis, several preventive strategies under investigation
      target the androgen axis. Epidemiologic and basic studies implicate dietary
      factors in prostate cancer development and suggest that altering diet may
      influence prostate cancer risk and progression. Many of the micronutrients with
      preventive potential have antioxidant properties; cellular defenses against
      oxidative stresses are likely to be crucial in reducing prostate carcinogenesis.
      This article summarizes the current status and opportunities in prostate cancer
      prevention.

PMID- 11525292
TI  - Vaccines as treatment strategies for relapsed prostate cancer: approaches for
      induction of immunity.
AB  - Prostate cancer is a important tumor in which to evaluate vaccine strategies. It
      is associated with two well-characterized serum biomarkers, prostate specific
      antigen (PSA) and prostatic acid phosphatase, which enables the investigator to
      monitor the progress of the disease. There are well-studied but less well-known
      glycoprotein and glycolipid antigens on the surface of prostate cancer cells that
      may function as targets for immune recognition and attack. Conventional
      treatments such as chemical castration are often poorly tolerated. When
      initiation of hormonal therapy is controversial, alternative therapies with
      minimal side effects are a desirable approach. Vaccines represent a means by
      which the immune system can be stimulated in order to affect an antitumor
      response by means of recruiting a variety of different effector arms of the
      immune system. The varying approaches toward vaccine construction as treatment
      strategies for relapsed prostate cancer are described.

PMID- 11525293
TI  - Prostate cancer gene therapy.
AB  - Cancer-specific gene therapy is still in its infancy. Although the first gene
      therapy trials were initiated in the late 1980s, it was only more recently that
      the first successful treatment of a genetic disease was reported.3 The current
      problems with low efficiency of gene transfer coupled with the immunologic
      difficulties with certain vectors indicate that more effort needs to be directed
      at the basic science of gene transfer. Ultimately, successful cancer-specific
      gene therapy will require combinations of the lessons learned from the ex vivo
      and in vivo paradigms. The next generation of gene therapy trials likely will
      focus on combination therapy with conventional chemotherapeutic agents,
      differentiating agents, or radiation therapy. The obstacles to the development of
      gene-based human therapeutics (i.e., molecular medicine) are formidable, but the
      benefits are so great that eventually the technical issues of gene transfer
      methodology will be worked out, and ultimately this will become the standard of
      care, not only for inborn errors of metabolism, but also for cancer.

PMID- 11525294
TI  - Targeting apoptosis in prostate cancer.
AB  - The understanding of apoptotic pathways provides new insights into cancer
      therapy. Therapies that modulate these pathways may induce apoptosis or sensitize
      tumor cells to other agents. Because many of the components of these pathways are
      altered in tumor cells compared with normal cells, therapies that target these
      abnormal apoptotic proteins may be more selective than traditional cytotoxic
      agents. Difficulties include the translation of the knowledge of these pathways
      into clinical trials and monitoring the predicted biologic effects in patients.
      The continued study of new targets, agents capable of modulating these targets,
      and markers of biologic effect in patients should improve clinical results.

PMID- 11525295
TI  - Paclitaxel and docetaxel in prostate cancer.
AB  - Although their ultimate value in prostate cancer therapy remains to be defined in
      randomized trials, docetaxel and paclitaxel are active agents in HRPC.
      Combination therapies using either of these taxanes plus oral EMP show
      reproducible antitumor activity that appears to be greater and more durable than
      that of single-agent treatment. Although the optimal combination and schedule
      have not been determined, weekly paclitaxel and EMP and docetaxel given every 3
      weeks or by weekly infusion with EMP are useful treatment options for patients
      with progressive HRPC. The gastrointestinal toxicity of EMP has been reduced by
      intermittent rather than continuous administration, and other toxicities may be
      reduced further by use of intravenous EMP. Although there has been progress, the
      median time to progression of 5 to 6 months for current taxane-based therapies
      suggests that they will not have major impact on overall survival for patients
      with HRPC. Greater benefit may be possible earlier in the course of prostate
      cancer, and the activity of the taxane-EMP combinations is sufficient to justify
      clinical trials of adjuvant or neoadjuvant chemotherapy for selected groups of
      patients with locally advanced and poor-prognosis tumors. Armed with many new
      molecularly targeted agents that may interact favorably with taxanes, it should
      be possible to build on current antimicrotubule regimens to improve activity in
      HRPC. Taxane-EMP combinations provide a platform on which to test additional
      agents that may enhance the apoptotic response or circumvent cellular stress
      adaptations that confer drug resistance. Further elucidation of signaling
      pathways that regulate microtubule dynamics and programmed cell death after
      exposure to microtubule inhibitors would provide a more rational guide for
      integrating specific inhibitors of signal transduction with current taxane-based
      therapies. Pharmacokinetic and pharmacodynamic studies will play a key role in
      the development of future taxane-based therapies for prostate cancer.

PMID- 11525296
TI  - New agents for prostate cancer.
AB  - Given the poor results with currently available therapies, it is imperative that
      new treatments be developed for patients with advanced prostate cancer. The next
      generation of therapies will include many novel biologic agents targeted at
      molecular defects in the cancer cell. Investigating the efficacy and safety of
      these compounds and evaluating their utility in combination with traditional
      therapies such as chemotherapy or radiotherapy are major goals of prostate cancer
      clinical research for the next decade.

PMID- 11525298
TI  - Clinical conduct and nursing quality of life in prostate cancer.
AB  - Recent advances in cancer therapy and supportive care have increased patient
      survival and improved quality of life. These advances have led to an increase in
      the responsibilities of nurses caring for these patients. Knowledge of new drugs,
      mode of action, expected side effects, and benefits, including effects on QOL,
      are essential. Nurses are vital to the safety and the quality of life that
      patients may experience while participating in clinical trials.

PMID- 11525297
TI  - Complementary and alternative therapies for advanced prostate cancer.
AB  - This article reviews complementary and alternative therapies for advanced
      prostate cancer. This is not a comprehensive survey of nontraditional therapies
      for prostate cancer. Rather, this review focuses on alternative and complementary
      therapies with published studies to evaluate efficacy and safety. Three areas are
      addressed: alternative forms of hormonal therapy, management of side effects of
      hormonal therapy, and management of skeletal complications.

PMID- 11525299
TI  - Internet oncology: increased benefit and risk for patients and oncologists.
AB  - Whether the benefits will outweigh the risks of electronic health care remains to
      be seen, and to a large extent the question is moot; consumers, providers, and
      interested third parties have ensured its existence. One can surmise, or at least
      hope, that all interested parties will become increasingly sophisticated in both
      the delivery and consumption of e-health information, and that ultimately
      consumer, advocate, and physician demands will help shape the industry into a
      self-regulated entity that balances the need for high-grade information with a
      commitment to the principles of privacy and autonomy.

PMID- 11525300
TI  - Gastric cancer.

PMID- 11525301
TI  - Gene therapy for gastric cancer: problems and prospects.

PMID- 11525302
TI  - The management of early gastric cancer.

PMID- 11525303
TI  - Modern staging in gastric cancer.

PMID- 11525304
TI  - Management of complications after gastrectomy with extended lymphadenectomy.

PMID- 11525305
TI  - Cancer of the esophagogastric junction.
AB  - In the Western world, there has been an alarming rise in the incidence and
      prevalence of adenocarcinoma arising at the esophagogastric junction during
      recent decades. Epidemiological, clinical and pathological data support a sub
      classification of adenocarcinomas arising in the vicinity of the esophagogastric
      junction (AEG) into adenocarcinoma of the distal esophagus (Type I), true
      carcinoma of the cardia (Type II) and subcardial carcinoma (Type III). While
      most, if not all, adenocarcinomas of the distal esophagus arise from areas with
      specialized intestinal metaplasia, which develop as a consequence of chronic
      gastroesophageal reflux, the etiology and pathogenesis of true carcinoma of the
      gastric cardia and subcardial gastric cancer is not clear at present. Although a
      subgroup of true carcinomas of the gastric cardia may also develop within short
      segments of intestinal metaplasia at the esophagogastric junction, a causal
      relation between these tumors and gastroesophageal reflux has been difficult to
      establish. Irrespective of the etiology, a complete removal of the primary tumor
      and its lymphatic drainage has to be the primary goal of any surgical approach to
      adenocarcinoma of the esophagogastric junction. Our experience in the management
      of more than 1000 such patients during the past 18 years suggests that an
      individualized therapeutic strategy oriented by tumor type and stage results in
      survival rates superior to those reported with a more indiscriminate approach.
      This individualized strategy prescribes a transmediastinal esophagectomy with
      lymphadenectomy in the lower posterior mediastinum and along the celiac axis for
      Type I tumors, extended total gastrectomy with transhiatal resection of the
      distal esophagus and D2 lymphadenectomy for Type II and Type III tumors, a
      limited resection of the esophagogastric junction and distal esophagus with
      interposition of a pedicled jejunal segment for uT1N0 tumors, and neoadjuvant
      chemotherapy followed by resection for uT3/T4 tumors. Extensive preoperative
      staging is essential to allow correct selection of the appropriate therapeutic
      strategy using this tailored approach.

PMID- 11525306
TI  - The use of molecular biology in diagnosis and prognosis of gastric cancer.
AB  - The investigation of molecular and genetic changes in gastric cancer has brought
      new insights into the pathogenesis of the disease. Knowledge of the genetic
      abnormalities and altered molecules could be used for differential diagnosis in
      case of an unknown primary tumor, allows their evaluation as prognostic factors,
      and could open novel avenues for more specific clinical interventions. Clinically
      relevant molecules whose expression or structure is altered include the
      plasminogen activator and its inhibitor plasminogen activator inhibitor type 1,
      the cell cycle regulator cyclin E, epidermal growth factor, the apoptosis
      inhibitor bcl-2, the cell adhesion molecule E-cadherin, and the multifunctional
      protein beta-Catenin. In addition, genetic instability is commonly seen. Gene
      amplification and protein overexpression of the growth factor receptors c-erbB2
      and K-sam may be prognostic factors for intestinal- and diffuse-type gastric
      cancer, respectively. There has long been evidence for a genetic predisposition
      to gastric cancer by epidemiological studies and case reports. Very recently,
      germ line mutations of E-cadherin have been identified that are responsible for a
      dominantly inherited from of diffuse-type gastric cancer and could be used to
      identify individuals that are at high risk. The clinical implications of the
      recent findings for diagnosis, prognosis, therapy, and risk assessment are
      discussed.

PMID- 11525308
TI  - General use of animal models for investigation of the physiology of erection.
AB  - In review, animal models have accounted significantly for the amazing strides
      made in the field of sexual dysfunction research. Fundamentally, they have
      offered a unique experimental approach to test many hypotheses regarding sexual
      function. Since their early use for sexual physiology research, there has been
      increasing sophistication using animals involving techniques for stimulating and
      monitoring sexual responses. One specific area that has been advanced is the use
      of conscious animal models to obtain a better sense of the natural contexts for
      sexual physiology and to avoid pharmacological interference associated with
      anesthetics. Another area of interest is the increasing use of simple but valid
      techniques to record and assess sexual responses. Efforts to develop and evaluate
      animal models that replicate disorders of sexual function have also been most
      advantageous. In the future, animal models will remain useful. The expanded
      applications of animal models include the study of predisposing disease states
      associated with sexual dysfunction and the study of all aspects of sexual
      dysfunction, in both male and female subjects. Continued judgment must be
      applied, understanding the advantages of one or another animal model, to explore
      questions and provide answers that are most scientifically relevant to the human
      condition. The promise of advancing therapies in this field indicates the
      additional prominent role for animals for the purposes of drug development.

PMID- 11525309
TI  - Pathophysiologic basis of erectile dysfunction. What can we learn from animal
      models?

PMID- 11525310
TI  - Rodents in impotence research: functional and genetic aspects.

PMID- 11525311
TI  - Rabbits as models for impotence research.
AB  - The anesthetized rabbit model is useful and has many advantages: ability to
      perform neurophysiological studies; more administration routes, including
      intracavernous injection; haemodynamic measurements in parallel to measurements
      of intracavernous pressure or penile volume; and direct measurement of
      intracavernosal pressure and blood flow. This model has been evaluated with many
      different types of drugs. The conscious rabbit model is a simple and valid model
      for the assessment of compounds with potential for treatment of ED. It offers
      several methodological advantages as a screening model for compounds with
      erection stimulating properties. It was clearly successful in demonstrating the
      efficacy and the mechanism of the new potent and selective PDE5 inhibitor
      vardenafil. The model was also effective in demonstrating erection-generating
      properties through other mechanisms, eg PDE3 inhibitors and alpha-receptor
      blockers. In conclusion, both anaesthetized rabbit model and the newly developed
      conscious-rabbit models are well-suited for studies in impotence research.

PMID- 11525312
TI  - Functional measurements of penile erection in feline, canine and primate animal
      models.

PMID- 11525313
TI  - Experimental models for the investigation of female sexual function and
      dysfunction.
AB  - There have been limited anatomic and physiological investigations of the female
      sexual arousal response. A broader understanding of the physiologic mechanisms of
      female sexual arousal function is required to improve the management of women
      with sexual dysfunction. Three experimental test systems have been developed to
      understand better the biochemical and physiological mechanisms of female sexual
      arousal response. An in vivo animal model was developed to record physiological
      and hemodynamic changes in the clitoris and vagina following pelvic nerve
      stimulation and administration of vasoactive agents and physiological modulators.
      In vitro organ baths of clitoral and vaginal tissue were utilized to investigate
      mechanisms involved in the regulation of smooth muscle contractility. In
      addition, primary cell cultures of human and animal clitoral and vaginal smooth
      muscle cells were developed to investigate signal transduction pathways
      modulating smooth muscle tone. In vivo studies revealed hemodynamic changes in
      vagina and clitoris in response to pelvic nerve stimulation, vasodilators and
      physiological modulators. Organ bath studies have demonstrated that clitoral and
      vaginal smooth muscle tone is affected by non-adrenergic and non-cholinergic
      neurotransmitters, and the presence of functional alpha 1 and alpha 2 adrenergic
      receptors in these tissues has been established through biochemical studies.
      These changes are regulated by the tone of vascular and non-vascular smooth
      muscle in the vagina and clitoris. Primary cell culture studies have suggested
      that several physiological modulators such as vasoactive intestinal polypeptide
      (VIP), nitric oxide (NO), and prostaglandin E (PGE) regulate vaginal smooth
      muscle contractility. Data from experimental models have provided a preliminary
      understanding of the mechanisms of the female sexual arousal response.

PMID- 11525314
TI  - Evaluation of oral ro70-0004/003, an alpha1A-adrenoceptor antagonist, in the
      treatment of male erectile dysfunction.
AB  - Alpha-adrenoceptor antagonists have been used for the treatment of male erectile
      dysfunction (MED). Ro70-0004/003 (Ro70-0004) is a selective and orally active
      alpha1A-adrenoceptor antagonist. The objective of this study was to: (1)
      pharmacologically elucidate the alpha1-adrenoceptor subtype mediating
      norepinephrine-induced contraction of human isolated corpus cavernosal tissue and
      (2) conduct a clinical proof-of-concept study with Ro70-0004 to test the
      hypothesis that selective alpha1A-adrenoceptor blockade would improve erectile
      function in patients with MED. In vitro organ bath studies were conducted with
      strips of human isolated corpus cavernosal tissue obtained from patients
      undergoing penile prosthesis implantation. Prazosin, cyclazosin, RS-100329 and
      Ro70-0004/003 antagonized norepinephrine-induced contractile responses with
      affinity estimates (pK(B) or pA2) of 8.4, 7.3, 9.2 and 8.8, respectively,
      consistent with the singular involvement of alpha1A-adrenoceptor subtype. A
      clinical study (single center, observer-blind, randomized, placebo-controlled,
      extended period Latin-Square crossover design) was conducted in 24 male patients
      (mean age 44 y) with MED of no established organic cause to evaluate the efficacy
      of a 5-mg oral dose of Ro70-0004. The primary efficacy endpoint was the duration
      of rigidity > 60% at the base of the penis measured between 0.5 and 2.5 h post
      dose. Rigidity was assessed by penile plethysmography using the RigiScan Plus
      device during visual sexual stimulation. The safety and efficacy of Ro70-0004 was
      also assessed. A 50-mg dose of sildenafil was included as a positive control. For
      the primary efficacy endpoint, the mean duration of erection was 9.69 min
      following administration of placebo, 8.28 min following Ro70-0004, and 22.64 min
      following sildenafil. Only the difference between sildenafil and placebo reached
      statistical significance (P < 0.05). A similar pattern was observed when
      measuring a duration of rigidity > 80% at the base of the penis (secondary
      endpoint). Ro70-0004 was safe and generally well tolerated (only two out of 20
      patients reported at least one adverse event). The highly selective alpha1A
      adrenoceptor antagonist, Ro70-0004, given at a single dose of 5 mg, did not
      improve erectile function when compared to placebo.

PMID- 11525315
TI  - Traumatic arteriogenic erectile dysfunction: a rat model.
AB  - We developed a rat model of traumatic arteriogenic erectile dysfunction (ED) for
      the study of vasculogenic ED. Bilateral ligation of the internal iliac artery was
      performed on 30 three-month old male Sprague-Dawley rats as an experimental
      group. The control group consisted of 12 rats which underwent dissection of the
      internal iliac artery without ligation. Before their euthanization at 3 days, 7
      days, and 1 month (10 rats in the experimental group and four rats in the control
      group at each time point), erectile function was assessed by electrostimulation
      of the cavernous nerves. Penile tissues were collected for nicotinamide adenine
      dinucleotide phosphate (NADPH) diaphorase staining, trichrome staining, electron
      microscopy and RT-PCR for transforming growth factor beta (TGF-beta1), insulin
      like growth factor-I (IGF-I) and fibroblast growth factors (FGF) mRNA expression.
      Electrostimulation of the cavernous nerves revealed a highly significant
      declining of the intracavernous pressure after 3 and 7 days. No significant
      recovery of erectile function was noted at 1 month. Histology showed degeneration
      of the dorsal nerve fibers in all experimental rats. There was little decrease in
      the bulk of intracavernous smooth muscle in the experimental rats euthanazed 7
      and 30 days. NADPH diaphorase staining revealed a significant decrease in nitric
      oxide synthase (NOS) containing nerve fibers in the dorsal and intracavernosal
      nerves in all rats in the experimental group. Electron microscopy showed a
      variety of changes such as collapse of sinusoids, increased cell debris,
      fibroblast and myofibroblast loss, intracellular deposition of fat and collagen
      and fatty degeneration. RT-PCR revealed up-regulation of TGF-beta1 after 3 days
      but not after 7 days or 1 month. There is no significant difference in IGF-I or
      FGF expression between the experimental and control group. Bilateral ligation of
      internal iliac arteries produces a reliable animal model for traumatic
      arteriogenic ED. Further studies are needed to investigate the molecular
      mechanism of ED in this model.

PMID- 11525316
TI  - Intracavernous injections: still the gold standard for treatment of erectile
      dysfunction in elderly men.
AB  - The objective of this work was to determine the effectiveness of intracavernous
      injections (ICI) of vasoactive drugs in elderly men with erectile dysfunction and
      to compare the results obtained with the injection of two different drug
      combinations. It was a case control study. The sample consisted of 300 men, 63-85
      y of age (mean 67.1) with erectile dysfunction of organic origin. Among the
      patients 180 underwent first trial with injection of prostaglandin E1 (PE).
      Further on these 180 patients and another 120 (in total 300 patients) were
      treated with a triple combination of papaverine hydrochlorate, phentolamine
      messylate and prostaglandin E1 (PPR). The number of responders to the injection
      of either PE alone or the drug combination was recorded. The quality of the
      erections was evaluated in the outpatient clinic by the medical staff and through
      patient's report after home trial. The average volume of either PE or PPR
      necessary to obtain a functional erection was measured. We observed a
      statistically significant association between the results obtained after the
      injection of PPR as compared to PE (chi2 with 2 d.f.: 34.666; P= < 0.001). A
      functional erection was obtained in 224/300 (74.7%) after the injection of PPR as
      compared to 87/180 men (48.3%) treated with PE. The average volume of PPR
      necessary to obtain a functional erection was 0.35+/-0.14 ml whereas that of PE
      was 1.3+/-0.3 ml. intracavernous injection of vasoactive drugs is still one of
      the most successful therapies for patients suffering from organic impotence. It
      is less effective in the older age group as compared to younger. However, if this
      form of therapy is chosen for aged men the triple combination therapy (PPR)
      yields a higher response rate than that obtained with prostaglandin alone.

PMID- 11525317
TI  - Severe erectile dysfunction is a marker for hyperprolactinemia.
AB  - The need for routine prolactin (PRL) measurement in the initial evaluation of
      erectile dysfunction (ED) has been questioned because of the low rate of
      hyperprolactinemia (HP) in these men and the costs involved. In addition, it is
      widely thought that sexual desire problems are a good clinical marker for HP
      and/or low testosterone in men with ED. Within a 15-month period, 844 consecutive
      PRL and sexual hormone determinations were conducted in men at the Kingston
      General Hospital. Of these patients, 138 were comprehensively evaluated at the
      first visit for ED and completed the International Index of Erectile Function
      (IIEF). In the 138 patients, 2.2% had severe hyperprolactinemia (>35 ng/ml),
      within the range of 1-5% previously reported. No correlation between initial
      prolactin value and the sexual desire domain or the erectile function domain
      (EFD) of the IIEF was found for this population. However, all cases of severe HP
      were found to occur in men who scored less than 10 in the EFD of the IIEF. Low
      libido is widely accepted as a marker of HP. In this study, HP was found in
      patients not reporting major problems with a desire disorder. Clinically
      significant HP may be reliably found with routine biochemical evaluation and in
      this series was not detected in patients with EFD scores above 10. A routine PRL
      measurement is inexpensive and early detection of a serious and treatable disease
      may afford greater therapeutic success.

PMID- 11525318
TI  - Long-term follow-up on use of pericardial graft in the surgical management of
      Peyronie's disease.
AB  - We have previously reported on the use of Tutoplast cadaveric pericardium as an
      alternative material for grafting the tunica albugineal defect after Peyronie's
      plaque excision with satisfactory results in 11 patients. We now review long-term
      outcomes in this cohort of men. Eleven patients with significant penile curvature
      interfering with sexual intercourse were evaluated after at least 12 months of
      conservative therapy. All patients underwent pre-operative evaluation, including
      penile duplex Doppler ultrasound studies. Chemically processed and gamma
      irradiated pericardium (Biodynamics International, Parsippany, NJ) was used to
      graft the cavernosal defect after surgical excision of the penile plaque. Three
      patients simultaneously underwent placement of penile prostheses secondary to
      documented erection problems identified at duplex Doppler ultrasound evaluation.
      The long-term postoperative complications and erectile function were evaluated
      with a mean follow-up of 30 months (range 25-35 months). All patients reported
      resolution of penile curvature allowing for normal sexual function after a mean
      follow-up of the first 14 months. Thirty months after placement of cadaveric
      pericardium, the three prosthetic patients still reported excellent sexual
      function. For the eight patients who did not undergo placement of a prosthesis,
      three with small to medium plaque size (<2 x 5 cm) continued to do well. The
      remaining five patients with a large plaque size (>2 x 5 cm) did well initially,
      but later reported difficulty maintaining erection due to venous leakage, thus
      they are currently using either a vacuum constriction device or an Actis ring.
      Three out of these five venous leakage patients had ventral plaques; two had
      dorsal plaques, one of significant size (4 x 5 cm). We conclude that for those
      patients who do not undergo placement of a prosthesis, a better long-term outcome
      is observed when the plaque is small to medium in size (<2 x 5 cm) and dorsally
      located. Patients with ventral plaque, extreme curvature, or plaque size >4 x 5
      cm were more likely to have venoocclusive dysfunction, necessitating further
      intervention.

PMID- 11525319
TI  - Quantification of F-18 FDG PET images in temporal lobe epilepsy patients using
      probabilistic brain atlas.
AB  - A probabilistic atlas of the human brain (Statistical Probabilistic Anatomical
      Maps: SPAM) was developed by the international consortium for brain mapping
      (ICBM). It is a good frame for calculating volume of interest (VOI) in many
      fields of brain images. After calculating the counts in VOI using the product of
      probability of SPAM images and counts in FDG images, asymmetric indices (AI) were
      calculated and used for finding epileptogenic zones in mesial temporal lobe
      epilepsy (mTLE). FDG PET images from 18 surgically confirmed mTLE patients and 22
      age-matched controls were spatially normalized to the average brain MRI template
      of ICBM. Counts from normalized PET images were multiplied with the probability
      of 12 VOIs from SPAM images in both temporal lobes. Finally AI were calculated on
      each pair of VOIs, and compared with visual assessment. If AI of mTLE patients
      were not within 2.9 standard deviation from those of normal control group (P <
      0.008; Bonferroni correction for P < 0.05), epileptogenic zones were considered
      to be found successfully. The counts of VOIs in the normal control group were
      symmetric (AI < 4.3%, paired t test P > 0.05) except for those of the inferior
      temporal gyrus (P < 0.001). By AIs in six pairs of VOIs, PET in mTLE had deficit
      on one side (P < 0.05). Lateralization was correct in only 14/18 of patients by
      AI, but 17/18 were consistent with visual inspection. In three patients with
      normal AI, PET images were symmetric on visual inspection. The asymmetric indices
      obtained by taking the product of the statistical probability anatomical map and
      FDG PET, correlated well with visual assessment in mTLE patients. SPAM is useful
      for the quantification of VOIs in functional images.

PMID- 11525320
TI  - Cerebral activation associated with sexual arousal in response to a pornographic
      clip: A 15O-H2O PET study in heterosexual men.
AB  - This study attempted to use PET and 15O-H2O to measure changes in regional
      cerebral blood flow (rCBF) during sexual arousal evoked in 10 young heterosexual
      males while they watched a pornographic video clip, featuring heterosexual
      intercourse. This condition was compared with other mental setups evoked by
      noisy, nature, and talkshow audiovisual clips. Immediately after each clip, the
      participants answered three questions pertaining to what extent they thought
      about sex, felt aroused, and sensed an erection. They scored their answers using
      a 1 to 10 scale. SPM was used for data analysis. Sexual arousal was mainly
      associated with activation of bilateral, predominantly right, inferoposterior
      extrastriate cortices, of the right inferolateral prefrontal cortex and of the
      midbrain. The significance of those findings is discussed in the light of current
      theories concerning selective attention, "mind reading" and mirroring,
      reinforcement of pleasurable stimuli, and penile erection.

PMID- 11525321
TI  - The effect of stimulus repetition on cortical magnetic responses evoked by words
      and nonwords.
AB  - Stimulus repetition improves performance and modulates event-related brain
      potentials in word recognition tasks. We recorded evoked magnetic responses from
      bilateral temporal sites of the brain to determine the cortical area related to
      the word repetition effect. Fourteen Japanese volunteers read words or
      pronounceable nonwords, some of which occurred twice with a lag of eight items.
      Clear magnetic responses were observed bilaterally. In the left hemisphere, a
      reduction of the magnetic responses by repetition was observed for words but not
      for nonwords in the latency range of 300-500 ms poststimulus. The sources of the
      responses were estimated to be in the left perisylvian area adjacent to the
      auditory cortex and the left parietal area. Only the perisylvian source activity
      showed the reduction by the word repetition. The left perisylvian area was thus
      suggested to be related to the word repetition effect. The activity in this area
      might be associated with the lexical memory process.

PMID- 11525322
TI  - Auditory triggered mental imagery of shape involves visual association areas in
      early blind humans.
AB  - Previous neuroimaging studies identified a large network of cortical areas
      involved in visual imagery in the human brain, which includes occipitotemporal
      and visual associative areas. Here we test whether the same processes can be
      elicited by tactile and auditory experiences in subjects who became blind early
      in life. Using positron emission tomography, regional cerebral blood flow was
      assessed in six right-handed early blind and six age-matched control volunteers
      during three conditions: resting state, passive listening to noise sounds, and
      mental imagery task (imagery of object shape) triggered by the sound of familiar
      objects. Activation foci were found in occipitotemporal and visual association
      areas, particularly in the left fusiform gyrus (Brodmann areas 19-37), during
      mental imagery of shape by both groups. Since shape imagery by early blind
      subjects does involve similar visual structures as controls at an adult age, it
      indicates their developmental crossmodal reorganization to allow perceptual
      representation in the absence of vision.

PMID- 11525323
TI  - Bayesian modeling of the hemodynamic response function in BOLD fMRI.
AB  - In functional magnetic resonance imaging (fMRI), modeling the complex link
      between neuronal activity and its hemodynamic response via the neurovascular
      coupling requires an elaborate and sensitive response model. Methods based on
      physiologic assumptions as well as direct, descriptive models have been proposed.
      The focus of this study is placed on such a direct approach that allows for a
      robust pixelwise determination of hemodynamic characteristics, such as time to
      peak or the poststimulus undershoot. A Bayesian procedure is presented that can
      easily be adapted to different hemodynamic properties in question and can be
      estimated without numerical problems known from nonlinear optimization
      algorithms. The usefulness of the model is demonstrated by thorough analyzes of
      the poststimulus undershoot in visual and acoustic stimulation paradigms.
      Further, we show the capability of this approach to improve analysis of fMRI data
      in altered hemodynamic conditions.

PMID- 11525324
TI  - Cortical correlates of gesture processing: clues to the cerebral mechanisms
      underlying apraxia during the imitation of meaningless gestures.
AB  - The clinical test of imitation of meaningless gestures is highly sensitive in
      revealing limb apraxia after dominant left brain damage. To relate lesion
      locations in apraxic patients to functional brain activation and to reveal the
      neuronal network subserving gesture representation, repeated H2(15O)-PET
      measurements were made in seven healthy subjects during a gesture discrimination
      task. Observing paired images of either meaningless hand or meaningless finger
      gestures, subjects had to indicate whether they were identical or different. As a
      control condition subjects simply had to indicate whether two portrayed persons
      were identical or not. Brain activity during the discrimination of hand gestures
      was strongly lateralized to the left hemisphere, a prominent peak activation
      being localized within the inferior parietal cortex (BA40). The discrimination of
      finger gestures induced a more symmetrical activation and rCBF peaks in the right
      intraparietal sulcus and in medial visual association areas (BA18/19). Two
      additional foci of prominent rCBF increase were found. One focus was located at
      the left lateral occipitotemporal junction (BA 19/37) and was related to both
      tasks; the other in the pre-SMA was particularly related to hand gestures. The
      pattern of task-dependent activation corresponds closely to the predictions made
      from the clinical findings, and underlines the left brain dominance for
      meaningless hand gestures and the critical involvement of the parietal cortex.
      The lateral visual association areas appear to support first stages of gesture
      representation, and the parietal cortex is part of the dorsal action stream.
      Finger gestures may require in addition precise visual analysis and spatial
      attention enabled by occipital and right intraparietal activity. Pre-SMA activity
      during the perception of hand gestures may reflect engagement of a network that
      is intimately related to gesture execution.

PMID- 11525325
TI  - A neurocognitive account of frontal lobe involvement in orthographic lexical
      retrieval: an fMRI study.
AB  - The present study aimed to examine the relationship between activation induced by
      an orthographic lexical retrieval (OLR) task and performance across time on the
      standard clinical version of OLR, the Controlled Oral Word Association Test
      (COWAT). The number of significantly activated pixels in a frontal lobe region of
      interest (encompassing middle and inferior frontal gyri) were measured for the
      left and right cerebral hemispheres in 20 volunteers. A relationship between the
      pixel count and the total number of words retrieved during the COWAT was found
      for the left but not the right hemisphere. Further examination of the left-sided
      relationship showed that the number of pixels in the left middle frontal region
      of interest correlated significantly with the second, but not the first, 30-s
      COWAT epoch. By contrast, the first epoch, but not the second, correlated
      significantly with the pixel count within the left inferior frontal region of
      interest. These relationships suggest differential involvement of dorsolateral
      and ventrolateral prefrontal cortex in specific cognitive processes fundamental
      to the production of language. Interindividual variation in activation levels may
      reflect underlying differences in cognitive processing capacity. This study is
      the first attempt to examine the relationship between fMRI activation and
      standard verbal fluency performance.

PMID- 11525326
TI  - Mind reading: neural mechanisms of theory of mind and self-perspective.
AB  - Human self-consciousness as the metarepresentation of ones own mental states and
      the so-called theory of mind (TOM) capacity, which requires the ability to model
      the mental states of others, are closely related higher cognitive functions. We
      address here the issue of whether taking the self-perspective (SELF) or modeling
      the mind of someone else (TOM) employ the same or differential neural mechanisms.
      A TOM paradigm was used and extended to include stimulus material that involved
      TOM and SELF capacities in a two-way factorial design. A behavioral study in 42
      healthy volunteers showed that TOM and SELF induced differential states of mind:
      subjects assigned correctly first or third person pronouns when providing
      responses to the stimuli. Following the behavioral study, we used functional
      magnetic resonance imaging (fMRI) in eight healthy, right-handed males to study
      the common and differential neural mechanisms underlying TOM and SELF. The main
      factor TOM led to increased neural activity in the anterior cingulate cortex and
      left temporopolar cortex. The main factor SELF led to increased neural activity
      in the right temporoparietal junction and in the anterior cingulate cortex. A
      significant interaction of both factors TOM and SELF was observed in the right
      prefrontal cortex. These divergent neural activations in response to TOM and SELF
      suggest that these important differential mental capacities of human self
      consciousness are implemented at least in part in distinct brain regions. Press

PMID- 11525327
TI  - An event-related fMRI study of overt and covert word stem completion.
AB  - In fMRI studies of language processing, it would be extremely useful to obtain
      high-quality images during tasks requiring spoken output. Recent studies have
      suggested that this may be possible, particularly if event-related fMRI methods
      are used. This study assesses the feasibility of acquiring interpretable images
      during speech by applying event-related methods to visual word stem completion, a
      task that has been studied extensively. On each trial, a different three-letter
      word stem (e.g., COU) was presented visually and subjects were required to
      generate a word beginning with that stem (e.g., COUSIN). In covert runs, subjects
      were instructed to say the word once to themselves, without moving their lips. In
      overt runs, subjects were instructed to say the word once aloud. Ten subjects
      were scanned during six overt runs and six covert runs at three presentation
      rates. Data were analyzed using an implementation of the general linear model
      making no assumptions about response shape. Images were relatively free of
      artifacts, and regions demonstrating task-related activation were similar to
      those reported in previous imaging studies. Regions active during overt task
      performance were similar to those active during covert task performance, with the
      addition of several regions commonly associated with motor aspects of speech
      production. Consistent with other studies, magnitude of activation was greater in
      the overt condition than in the covert condition, and there was a modest decrease
      in magnitude at the fastest presentation rate. Together, these results help to
      validate the use of event-related fMRI during tasks that require spoken output.
      Press

PMID- 11525328
TI  - A tool for comparison of PET and fMRI methods: calculation of the uncertainty in
      the location of an activation site in a PET image.
AB  - A technique for calculating the uncertainty in the location of an activation site
      in a PET image, without performing repeated measures, is presented. With the
      development of new fMRI methods for measuring cerebral hemodynamics,
      demonstration of the efficacy of these techniques will be critical to establish
      clinical utility. Comparisons with PET are a powerful tool for validating these
      new fMRI techniques. In addition to the fact that PET techniques are well
      established methods for making physiological measurements in vivo, PET methods
      are also free of the geometric distortions and nonuniform signal-to-noise
      artifacts (due to signal dropout) common in fMRI techniques. Comparisons reported
      previously have been limited by the large number of trials acquired in single
      subject fMRI studies and the small number of trials in a PET study (due to the
      radiation dose to the patient or the interscan delays for tracer decay). Our
      method calculates both the center of mass (CM) of a predefined region of interest
      and the uncertainty in the location of the CM using the preimage PET data
      (sinograms). Results of phantom studies demonstrate that our method is an
      unbiased measurement equivalent to that of repeated measures with a large number
      of images. Extension of this technique to estimate the uncertainty in the
      location of an activation site in a PET statistical parametric map will permit
      precise rigorous comparisons of PET and fMRI methods in single subjects without
      the constraints imposed by the relatively small number of PET measurements.

PMID- 11525329
TI  - Frontal cerebral perfusion dysfunction in elderly late-onset major depression
      assessed by 99MTC-HMPAO SPECT.
AB  - Baseline regional cerebral blood flow of thirty unmedicated late-onset unipolar
      major depressed patients over the age of 60 years and 20 sex-, age-, and vascular
      risk factor-matched healthy controls was imaged with single photon emission
      computed tomography, using technetium-99m hexamethylpropylene amine oxime as a
      tracer. To avoid errors of diagnosis--in particular, confusion between major
      depression and organic cognitive impairment--only treatment responders were
      included in the final sample. Statistically significant differences were observed
      in both left and right anterior frontal regions, with reduced uptake in depressed
      patients; these differences were more pronounced in the left hemisphere. Among
      patients, there was no correlation between regional cerebral blood flow and the
      severity of baseline symptoms. Our results support the hypothesis that certain
      neuroanatomic regions of the central nervous system may be functionally involved
      in elderly unipolar major depression, particularly in the late-onset subgroup.

PMID- 11525330
TI  - Pitfalls in the clustering of neuroimage data and improvements by global
      optimization strategies.
AB  - In this paper, we examined three vector quantization (VQ) methods used for the
      unsupervised classification (clustering) of functional magnetic resonance imaging
      (fMRI) data. Classification means that each brain volume element (voxel),
      according to a given scanning raster, was assigned to one group of voxels based
      on similarity of the fMRI signal patterns. It was investigated how the VQ methods
      can isolate a cluster that describes the region involved in a particular brain
      function. As an example, word processing was stimulated by a word comparison
      task. VQ analysis methodology was verified using simulated fMRI response
      patterns. It was demonstrated in detail that VQ based on global rather than local
      optimization of the objective function yielded a higher performance. Performance
      was measured in statistically relevant series of VQ attempts using several
      indices for goodness, reliability and efficiency of VQ solutions. Furthermore, it
      was shown that a poor local optimization caused either an underestimation or an
      overestimation of the stimulus-induced brain activation. However, this was not
      observed if the cluster analysis was based upon a global optimization strategy.

PMID- 11525331
TI  - A voxel-based morphometric study of ageing in 465 normal adult human brains.
AB  - Voxel-based-morphometry (VBM) is a whole-brain, unbiased technique for
      characterizing regional cerebral volume and tissue concentration differences in
      structural magnetic resonance images. We describe an optimized method of VBM to
      examine the effects of age on grey and white matter and CSF in 465 normal adults.
      Global grey matter volume decreased linearly with age, with a significantly
      steeper decline in males. Local areas of accelerated loss were observed
      bilaterally in the insula, superior parietal gyri, central sulci, and cingulate
      sulci. Areas exhibiting little or no age effect (relative preservation) were
      noted in the amygdala, hippocampi, and entorhinal cortex. Global white matter did
      not decline with age, but local areas of relative accelerated loss and
      preservation were seen. There was no interaction of age with sex for regionally
      specific effects. These results corroborate previous reports and indicate that
      VBM is a useful technique for studying structural brain correlates of ageing
      through life in humans.

PMID- 11525332
TI  - Comparison of auditory, somatosensory, and visually instructed and internally
      generated finger movements: a PET study.
AB  - We sought to determine how the pattern of cerebral activation, and in particular
      in frontal motor areas, during the performance of conditional motor tasks is
      dependent upon the modality of instruction (visual, auditory, or somatosensory).
      Regional cerebral blood flow (rCBF) changes with externally instructed movements
      were also compared with internally generated, self-paced, movements. We used
      positron emission tomography (PET) with the tracer H2(15O) to measure rCBF in 22
      healthy volunteers. External stimuli consisted of the randomized presentation of
      single or double impulses using a single modality for each condition. In the
      movement scans, the subjects used the index and middle fingers of their right
      hands to press a left button for a single and a right button for a double
      impulse, respectively. In the control scans, subjects were required to covertly
      distinguish a single from a double stimulus without a motor response. Data were
      analyzed using conventional subtraction techniques with a statistical threshold
      of Z > 2.33 with corrections for multiple comparisons. When the activation
      differences between the three externally instructed movement conditions were
      statistically compared, nonsignificant trends toward increased rCBF in the
      sensory cortex of the modality of the cue were observed but no differential
      activity in cortical motor areas. Internally generated movements, when compared
      to externally triggered movements, were associated with enhanced activation in
      bilateral medial and lateral premotor, dorsolateral prefrontal and superior
      parietal regions, largely confirming previous reports. The data indicate that, on
      a regional level, modality-specific processing in a conditional motor task does
      not occur in frontal motor areas and is probably confined to sensory areas.

PMID- 11525333
TI  - A longitudinal quantitative MRI study of community-based patients with chronic
      epilepsy and newly diagnosed seizures: methodology and preliminary findings.
AB  - Experimental and human data suggest that progressive cerebral damage may result
      from the cumulative effect of brief recurrent seizures. Longitudinal studies
      addressing this fundamental question, however, are lacking. We have addressed
      this need with a large prospective community-based observational study, which
      aims to rescan 154 patients with chronic active epilepsy and 90 patients with
      newly diagnosed seizures, after an interval of 3.5 years. Here, we describe the
      quantitative magnetic resonance methods used to identify subtle volume changes in
      hippocampal, cerebellar, and neocortical structures over time and report
      preliminary findings. Using this methodology, we have previously shown that we
      can reliably detect individual hippocampal volume (HV) and cerebellar volume
      (CBV) changes greater than 3.1 and 3.0%, respectively (Lemieux et al, 2000).
      Analysis of the first 53 subjects (24 patients with chronic active epilepsy, 9
      patients with newly diagnosed seizures, and 20 controls) has demonstrated
      significant HV losses in 4 individuals. Automated and semiautomated calculation
      has detected significant reductions in CBV, total brain volume, and gray matter
      volume in 2, 3, and 1 subject, respectively. There were no significant white
      matter volume losses detected. Data collected from rescanning the entire cohorts
      will help to provide further information on the relationship between recurrent
      seizures and secondary brain damage.

PMID- 11525334
TI  - Effects of acoustic gradient noise from functional magnetic resonance imaging on
      auditory processing as reflected by event-related brain potentials.
AB  - The processing of sound changes and involuntary attention to them has been widely
      studied with event-related brain potentials (ERPs). Recently, functional magnetic
      resonance imaging (fMRI) has been applied to determine the neural mechanisms of
      involuntary attention and the sources of the corresponding ERP components. The
      gradient-coil switching noise from the MRI scanner, however, is a challenge to
      any experimental design using auditory stimuli. In the present study, the effects
      of MRI noise on ERPs associated with preattentive processing of sound changes and
      involuntary switching of attention to them were investigated. Auditory stimuli
      consisted of frequently presented "standard" sounds, infrequent, slightly higher
      "deviant" sounds, and infrequent natural "novel" sounds. The standard and deviant
      sounds were either sinusoidal tones or musical chords, in separate stimulus
      sequences. The mismatch negativity (MMN) ERP associated with preattentive sound
      change detection was elicited by the deviant and novel sounds and was not
      affected by the prerecorded background MRI noise (in comparison with the
      condition with no background noise). The succeeding positive P3a ERP responses
      associated with involuntary attention switching elicited by novel sounds were
      also not affected by the MRI noise. However, in ERPs to standard tones and
      chords, the P1, N1, and P2 peak latencies were significantly prolonged by the MRI
      noise. Moreover, the amplitude of the subsequent "exogenous" N2 to the standard
      sounds was significantly attenuated by the presence of MRI noise. In conclusion,
      the present results suggest that in fMRI the background noise does not interfere
      with the imaging of auditory processing related to involuntary attention.

PMID- 11525335
TI  - Location- or feature-based targeting of peripheral attention.
AB  - Using event-related fMRI we determined the differential effects of feature-
      versus location-based cues for directing peripheral attention. Pairs of same
      color targets appeared on the left and on the right. A predictive cue indicated
      whether the subsequent targeting of attention would be based on location (left
      versus right) or color (red versus blue). Subjects had to press a button when the
      relevant pair of targets (in the cued side of space or of the cued color) were
      identical in shape. The feature-based cue thus also led to a "global" expectancy
      of targets on either side of space whereas the location-based cue elicited a more
      "focal" expectancy limited to one side of space. The right inferior parietal
      lobule was more active when attention was targeted on the basis of location than
      of color. There was no difference between left-sided or right-sided attention in
      this region, indicating that it mediated the targeting to both sides of space.
      These results show that the right inferior parietal cortex plays a relatively
      selective role in mediating location-based and spatially focal modes of
      attentional deployment. Its relatively equal activation for leftward and
      rightward attentional shifts is also consistent with models of right hemispheric
      dominance of spatial attention.

PMID- 11525336
TI  - Direct comparison of prefrontal cortex regions engaged by working and long-term
      memory tasks.
AB  - Neuroimaging studies have suggested the involvement of ventrolateral,
      dorsolateral, and frontopolar prefrontal cortex (PFC) regions in both working
      (WM) and long-term memory (LTM). The current study used functional magnetic
      resonance imaging (fMRI) to directly compare whether these PFC regions show
      selective activation associated with one memory domain. In a within-subjects
      design, subjects performed the n-back WM task (two-back condition) as well as LTM
      encoding (intentional memorization) and retrieval (yes-no recognition) tasks.
      Additionally, each task was performed with two different types of stimulus
      materials (familiar words, unfamiliar faces) in order to determine the influence
      of material-type vs task-type. A bilateral region of dorsolateral PFC (DL-PFC; BA
      46/9) was found to be selectively activated during the two-back condition,
      consistent with a hypothesized role for this region in active maintenance and/or
      manipulation of information in WM. Left frontopolar PFC (FP-PFC) was also found
      to be selectively engaged during the two-back. Although FP-PFC activity has been
      previously associated with retrieval from LTM, no frontopolar regions were found
      to be selectively engaged by retrieval. Finally, lateralized ventrolateral PFC
      (VL-PFC) regions were found to be selectively engaged by material-type, but
      uninfluenced by task-type. These results highlight the importance of examining
      PFC activity across multiple memory domains, both for functionally
      differentiating PFC regions (e.g., task-selectivity vs material-selectivity in DL
      PFC and VL-PFC) and for testing the applicability of memory domain-specific
      theories (e.g., FP-PFC in LTM retrieval).

PMID- 11525337
TI  - Acupuncture produces central activations in pain regions.
AB  - Acupuncture is largely used for pain control in several pathological conditions.
      Its effects on the central nervous system are not well defined. We investigated
      the effect of the application of acupuncture to 13 normal subjects (males, 21-32
      years). H2(15)O bolus PET scans were read before the application of the needles
      (Rest, R) and after 25 min of needle insertion. Data were acquired by scanning in
      3-D mode. The acupuncture application, true acupuncture (TA), was alternated to a
      placebo needle application (PA) in two different sequences (seven and six
      subjects, respectively), either R,PA,R, TA or R,TA,R,PA, a period of 15 min being
      left after every first TA or PA to allow for the recovery of basal conditions.
      Here we show that classic acupuncture activates the left Anterior Cingulus, the
      Insulae bilaterally, the Cerebellum bilaterally, the left Superior Frontal Gyrus,
      and the right Medial and Inferior Frontal Gyri. Most of the activated areas are
      shared with areas activated in acute and chronic pain states as described in the
      literature. Thus acupuncture appears to act by activating areas also involved in
      pain. This indicates that acupuncture could relief pain by unbalancing the
      equilibrium of distributed pain-related central networks.

PMID- 11525338
TI  - Anterior medial temporal lobe activation during attempted retrieval of encoded
      visuospatial scenes: an event-related fMRI study.
AB  - Various studies have shown that the medial temporal lobe (MTL), which consists of
      the hippocampus and parahippocampal gyrus, is important for episodic memory.
      Earlier fMRI studies substantiated this role by showing activation upon encoding
      of visuospatial scenes. In this study we used event-related fMRI to study whether
      the cognitive process of retrieval of visuospatial scenes, tested with the use of
      a recognition paradigm, also activates the MTL. Nine subjects (mean age 24 years)
      were presented previously studied color pictures (old) and pictures they had
      never seen before (new) in a mixed trial design. Data analysis allowed
      calculation of the fMRI response of correct judgments on new pictures, old
      pictures, and false judgments. Since we used previously encoded color pictures as
      old stimuli, we also included an encoding paradigm in the current set of
      experiments. This allowed us to compare encoding and recognition activation in
      the MTL of exactly the same pictures in the same subjects. Correct judgments on
      new pictures showed an increased activation in the anterior parahippocampus
      bilaterally and the right anterior hippocampus compared to judgments on old
      pictures in the recognition experiment. The former judgments took significantly
      longer, indicating that retrieval of successfully stored information is less
      demanding than the effort to retrieve nonencoded information. A comparison of the
      two experimental data sets showed evidence for a functional segregation of
      encoding and retrieving color pictures. We conclude that the left posterior
      parahippocampal gyrus responds during encoding, while on the other hand the left
      anterior parahippocampal gyrus and the right anterior hippocampus were more
      strongly involved in retrieval.

PMID- 11525339
TI  - Reorganization of frontal systems used by alcoholics for spatial working memory:
      an fMRI study.
AB  - Chronic alcoholism is associated with impairment in sustained attention and
      visual working memory. Thus, alcoholics have reduced ability, but not necessarily
      inability, to perform these executive tasks, assumed to be subserved by regions
      of prefrontal cortex. To identify neural substrates associated with this
      impairment, we used functional MRI (fMRI) to determine whether alcoholics invoke
      the same or different brain systems as controls when engaged in working memory
      tasks that the two groups were able to perform at equivalent levels. The fMRI
      spatial working memory paradigm instructed subjects to respond with a button
      press when a target position was either in the center of the field (match to
      center) or matched the spatial position of one presented two items previously
      (match 2-back) or to rest. Using whole-brain fMRI, alcoholics showed diminished
      activation frontal cortical systems compared to controls (bilateral dorsolateral
      prefrontal cortex) when responding 2-back vs rest. In the center vs rest
      contrast, the control group compared with the alcoholic group activated a large
      expanse of prefrontal cortex (including Brodmann areas 9, 10, and 45), whereas
      there was significantly greater activation by the alcoholic group relative to the
      control group localized more posteriorly and inferiorly in the frontal cortex
      (area 47). Examination of within group activation patterns revealed two different
      patterns of activation: the control group exhibited activation of the dorsal
      ("Where?") stream for visual spatial working memory processing, whereas the
      alcoholic group exhibited activation of the ventral ("What?") stream and
      declarative memory systems to accomplish the spatial working memory task. The
      differences in the pattern of brain activations exhibited by the alcoholic and
      control groups, despite equivalence in behavioral performance, is consistent with
      a functional reorganization of the brain systems invoked by alcoholic individuals
      or invocation of an inappropriate brain system when engaged in a visual spatial
      task requiring working memory.

PMID- 11525340
TI  - Working memory for location and time: activity in prefrontal area 46 relates to
      selection rather than maintenance in memory.
AB  - The role of the dorsal prefrontal cortex in working memory remains controversial.
      Influential proposals include a role in the maintenance of domain-specific
      information, and the processes of executive functions on remembered information.
      We used event-related functional magnetic resonance imaging to demonstrate a
      functional dissociation within prefrontal cortex in terms of the components of
      complex working memory tasks. The maintenance in working memory of spatial
      locations and their temporal order was associated with activation of area 8 and
      intraparietal cortex. In contrast, the selection of one location, according to
      its order, was associated with a distinct frontoparietal network, including
      dorsolateral prefrontal area 46, ventrolateral prefrontal cortex and anterior
      cingulate cortex and medial parietal cortex. The different contributions of these
      areas to selection are considered in the light of recent electrophysiological and
      lesion studies. We suggest a general role of the dorsolateral prefrontal area 46
      in attentional selection, including selection from within working memory.

PMID- 11525341
TI  - Measurement of the striatal dopamine transporter density and heterogeneity in
      type 1 alcoholics using human whole hemisphere autoradiography.
AB  - Dopaminergic mechanisms are involved in the positive reinforcing and addicting
      effects of alcohol. Positron emission tomography (PET) and single photon emission
      tomography (SPET) studies have indicated alterations in striatal dopamine
      transporters (DAT) and in presynaptic dopamine (DA) function in alcoholics,
      although also contradictory results have been reported. Normal variations in
      blood flow, metabolism, and receptor densities are apparently important to brain
      function. Such variations are known to decrease during pathophysiological
      processes, such as epilepsy, whereas normal receptor distributions are broadly
      heterogenous. We evaluated the densities and heterogeneities of striatal DAT in 8
      adult-onset, Cloninger type I alcoholics and 10 controls using [125I]N-(3
      iodoprop-2E-enyl)-2beta-carbomethoxy-3beta- (4'-methylphenyl)nortropane
      ([125I]PE2I) as a ligand for human postmortem whole hemisphere autoradiography,
      which provided high resolution images of the brain when compared with in vivo PET
      and SPET. The mean density and heterogeneity of DAT were markedly lower in the
      alcoholics. A significant linear correlation existed between DAT density and
      heterogeneity, as well as between DAT densities in the nucleus accumbens and in
      the dorsal striatum (caudate and putamen) in alcoholics, but not consistently in
      controls. The observed low DAT density and heterogeneity in the dorsal striatum
      suggest that type 1 alcoholics may have a dysfunctional DA system. These data
      indicate that human whole hemisphere autoradiography with the analysis of binding
      heterogeneity may be a relevant tool to measure pathological processes in the
      brain.

PMID- 11525342
TI  - Automatic segmentation of the ventricular system from MR images of the human
      brain.
AB  - An algorithm was developed that automatically segments the lateral and third
      ventricles from T1-weighted 3-D-FFE MR images of the human brain. The algorithm
      is based upon region-growing and mathematical morphology operators and starts
      from a coarse binary total brain segmentation, which is obtained from the 3-D-FFE
      image. Anatomical knowledge of the ventricular system has been incorporated into
      the method in order to find all constituting parts of the system, even if they
      are disconnected, and to avoid inclusion of nonventricle cerebrospinal fluid
      (CSF) regions. A test of the method on a synthetic MR brain image produced a
      segmentation overlap of 0.98 between the simulated ventricles ("model") and those
      defined by the algorithm. Further tests were performed on a large data set of 227
      1.5 T MR brain images. The algorithm yielded useful results for 98% of the
      images. The automatic segmentations had intra-class correlation coefficients of
      0.996 for the lateral ventricles and 0.86 for the third ventricle, with manually
      edited segmentations. Comparison of ventricular volumes of schizophrenia patients
      compared with those of healthy control subjects showed results in agreement with
      the literature.

PMID- 11525343
TI  - Adolescent cigarette smoking: health-related behavior or normative transgression?
AB  - Relations among measures of adolescent behavior were examined to determine
      whether cigarette smoking fits into a structure of problem behaviors-behaviors
      that involve normative transgression-or a structure of health-related behaviors,
      or both. In an ethnically and socioeconomically diverse sample of 1782 male and
      female high school adolescents, four first-order problem behavior latent
      variables-sexual intercourse experience, alcohol abuse, illicit drug use, and
      delinquency-were established and together were shown to reflect a second-order
      latent variable of problem behavior. Four first-order latent variables of health
      related behaviors-unhealthy dietary habits, sedentary behavior, unsafe behavior,
      and poor dental hygiene-were also established and together were shown to reflect
      a second-order latent variable of health-compromising behavior. The structure of
      relations among those latent variables was modeled. Cigarette smoking had a
      significant and substantial loading only on the problem-behavior latent variable;
      its loading on the health-compromising behavior latent variable was essentially
      zero. Adolescent cigarette smoking relates strongly and directly to problem
      behaviors and only indirectly, if at all, to health-compromising behaviors.
      Interventions to prevent or reduce adolescent smoking should attend more to
      factors that influence problem behaviors.

PMID- 11525344
TI  - Effects of the "Preparing for the Drug Free Years" curriculum on growth in
      alcohol use and risk for alcohol use in early adolescence.
AB  - Preparing for the Drug-Free Years (PDFY) is a curriculum designed to help parents
      learn skills to consistently communicate clear norms against adolescent substance
      use, effectively and proactively manage their families, reduce family conflict,
      and help their children learn skills to resist antisocial peer influences. This
      study examined the effects of PDFY on the trajectories of these factors, as well
      as on the trajectory of alcohol use from early to mid adolescence. The sample
      consisted of 424 rural families of sixth graders from schools randomly assigned
      to an intervention or a control condition. Data were collected from both parents
      and students at pretest, posttest, and 1-, 2- and 3 1/2-year follow-ups. Latent
      growth models were examined. PDFY significantly reduced the growth of alcohol use
      and improved parent norms regarding adolescent alcohol use over time.
      Implications for prevention and evaluation are discussed.

PMID- 11525345
TI  - Can mentoring or skill training reduce recidivism? Observational study with
      propensity analysis.
AB  - We compared juvenile offenders' recidivism following nonrandom assignment to
      juvenile diversion (JD, n = 137), JD plus skill training (ST, n = 55), or JD plus
      mentoring (MEN, n = 45). Intake characteristics that distinguished intervention
      groups were used to calculate assignment propensity scores. After propensity
      score blocking balanced intake characteristics, ST proved more cost effective
      than MEN, achieving a 14% relative reduction in recidivism at a savings of
      $33,600 per hundred youths. In ST, 37% were rearrested 2 years or more after
      intake, compared to 51% in MEN and 46% in JD. In two of five propensity
      subclasses, time to first rearrest was longer in ST (M = 767 days) than in MEN (M
      = 638 days) or JD (M = 619 days). These results argue for an experimental
      comparison of ST and MEN and for observational studies with propensity analysis
      when randomization to juvenile justice interventions is infeasible.

PMID- 11525346
TI  - Team awareness for workplace substance abuse prevention: the empirical and
      conceptual development of a training program.
AB  - This paper describes the empirical and theoretical development of a workplace
      training program to help reduce/prevent employee alcohol and drug abuse and
      enhance aspects of the work group environment that support ongoing prevention.
      The paper (1) examines the changing social context of the workplace (e.g.,
      teamwork, privacy issues) as relevant for prevention, (2) reviews studies that
      assess risks and protective factors in employee substance abuse (work
      environment, group processes, and employee attitudes), (3) provides a conceptual
      model that focuses on work group processes (enabling, neutralization of deviance)
      as the locus of prevention efforts, (4) describes an enhanced team-oriented
      training that was derived from previous research and the conceptual model, and
      (5) describes potential applications of the program. It is suggested that the
      research and conceptual model may help prevention scientists to assess the
      organizational context of any workplace prevention strategy. The need for this
      team-oriented approach may be greater among employees who experience psychosocial
      risks such as workplace drinking climates, social alienation, and policies that
      emphasize deterrence (drug testing) over educative prevention. Limitations of the
      model are also discussed.

PMID- 11525347
TI  - Tuberculosis: trends and the twenty-first century.
AB  - The global burden of tuberculosis is enormous, even if estimates are somewhat
      uncertain. The forces counteracting control measures, namely demographic factors,
      drug resistance, HIV, migration, poverty and marginalization, are enormous as
      well. With accelerated reforms in tuberculosis programs important progress can be
      made towards the control of tuberculosis early in the 21st century. This is
      confirmed by studying reports from countries where control measures have been
      implemented and sustained. Well-functioning programs can make good use of
      technological progress, such as improved tools for diagnosis and treatment, when
      these become available at an affordable cost. It is important now to use the
      opportunity of increased resources in order to reform tuberculosis programs. The
      biggest impact on global tuberculosis control in the 21st century can be made in
      Asia. Success in this part of the world depends on political commitment.
      Elsewhere, the main forces counteracting control measures are HIV in Africa and
      multidrug resistance in parts of Europe and the former Soviet Union. Here
      solutions are still on the drawing board. The long time-frame for tuberculosis
      control when using the currently recommended strategy, the uncertain impact of
      "improved" tools on this time-frame and the constant threat that political
      commitment will not be sustained are reasons why field workers look towards new
      technology in hope of progress in vaccine research. Here, the prospects are
      uncertain and the forecasted time-frame is long. Skeptics even doubt that an
      effective vaccine can be developed. However, when predicting progress it is
      important to realize that it is for the most part unpredictable.

PMID- 11525348
TI  - Helminths, human immunodeficiency virus and tuberculosis.
AB  - Helminth infections affect over a quarter of the world's population, especially
      in the developing countries. These long-lasting parasitic infections cause
      widespread immune activation and dysregulation, a dominant Th2 cytokine immune
      profile and an immune hyporesponsiveness state. Considering these profound immune
      changes and the similar geographic distributions of helminthic infections, HIV
      and tuberculosis (TB), we suggest that helminthic infections play a major role in
      the pathogenesis of AIDS and TB. They apparently make the host more susceptible
      to infection by HIV and Mycobacterium tuberculosis, and impair his/her ability to
      generate protective immunity against both infections. The implication of these
      ideas is that without eradication of helminth infections and/or modulation of the
      immune changes that they cause, HIV and TB vaccines may fail to confer protection
      against their respective infections in helminth-endemic areas.

PMID- 11525349
TI  - GB virus C/hepatitis G virus.
AB  - GB virus C (GBV-C), or hepatitis G virus (HGV), is a recently discovered
      enveloped RNA virus belonging to the Flaviviridae family. GBV-C/HGV is
      transmitted by contaminated blood and/or blood products, intravenous drug use,
      from mother to child, sexually, and possibly through close social contacts.
      Several reports indicate a high prevalence of GBV-C/HGV viremia (1-4%) within
      healthy populations in Europe and North America, and an even higher prevalence
      (10-33%) among residents in South America and Africa. GBV-C/HGV has been
      suggested to be a causative agent for non-A-non-E hepatitis. However, several
      contradictory observations suggest that its ability to cause hepatitis is
      questionable. Taken together most data suggest that GBV-C/HGV is not a major
      cause of liver disease despite recent data indicating that it may infect and
      replicate in hepatocytes.

PMID- 11525350
TI  - Epidemiological pattern of meningococcal disease in Valencia, Spain. Impact of a
      mass immunization campaign with meningococcal C polysaccharide vaccine.
AB  - The objective of this study was to define the epidemiological pattern of
      meningococcal disease in the autonomous region of Valencia, Spain, and the impact
      of a mass immunization campaign against serogroup C meningococcus. Data were
      obtained from a prospective surveillance program for invasive bacterial diseases
      in children < 15 y of age that began in the Valencia region on 1 December, 1995.
      During the period 1996-98, 213 cases of meningococcal disease were detected,
      representing an annual incidence of 11.3/100,000 children < 15 y. Serogroup C
      accounted for 31% and 38.5% of cases in 1996 and 1997, respectively (annual
      incidences of 2.9 and 5.4 cases/100,000 children < 15 y). An immunization
      campaign with the meningococcal C polysaccharide vaccine, which included all
      persons between 18 months and 19 y of age, began in late 1997 (vaccination
      coverage of 86%). In 1998, the annual incidence of meningococcal C disease fell
      to 1.4 cases per 100,000 children < 15 y of age. These results mirror the
      increase in the reported incidence of serogroup C meningococcal disease in Spain
      in the 1990s, a trend that was reversed after the introduction of the mass
      vaccination campaign. Meningococcal polysaccharide vaccine seems to be an
      effective public health tool for the management of this serious communicable
      disease.

PMID- 11525351
TI  - Antimicrobial susceptibility of Mycobacterium marinum determined by E-test and
      agar dilution.
AB  - Mycobacterium marinum is recognized as a cutaneous pathogen requiring antibiotic
      treatment. We compared the E-test with a reference agar dilution method for
      susceptibility testing of M. marinum to amikacin, ciprofloxacin, clarithromycin,
      doxycycline, rifampicin, trimethoprim-sulfamethoxazole and ethambutol. MICs
      obtained after 6 d showed agreement between the E-test and agar dilution within
      +/- 2 dilutions in 95% of all cases for amikacin, ciprofloxacin, doxycycline and
      rifampicin. Inhibitory concentrations of trimethoprim-sulfamethoxazole were
      difficult to define using the E-test because of gradually decreased growth in the
      presence of increasing concentrations. For clarithromycin, results were generally
      1-3 dilution steps lower with the E-test and for ethambutol they were often > 3
      dilution steps lower. These differences always appeared in the low MIC range and
      did not affect the categorization of the strains as susceptible to these 2
      antimicrobial agents. All strains were interpreted as susceptible to all tested
      antibiotics, except for doxycycline, according to recommended breakpoints.
      Overall, our results suggest that the E-test can be considered an alternative for
      susceptibility testing of certain antibacterial agents against M. marinum.

PMID- 11525352
TI  - Antibodies to Chlamydia pneumoniae in young Swedish orienteers.
AB  - During 1992-93 sera from 1790 Swedish elite orienteers were tested for antibodies
      to Chlamydia pneumoniae. The reason for this was that a cluster of 16 cases of
      sudden unexpected cardiac death had occurred among Swedish orienteers and DNA
      from C. pneumoniae had been found in the myocarditic heart and in the lung in 1
      of 2 deceased athletes in whom testing was feasible; in addition, C. pneumoniae
      IgG was found in all 5 cases where serum was available. Among the orienteers, the
      prevalence rates of IgG antibodies in males and females were 54% (n = 1194) and
      50% (n = 596), respectively. The corresponding figures for 319 male and female
      blood donors were 60% (n = 169) and 53% (n = 150), respectively. These
      differences are not statistically significant. Male orienteers had a lower
      prevalence of IgA antibodies than male blood donors (19% and 26%, respectively; p
      < 0.05), while no such difference was found in females (16% and 18%). The
      prevalence of IgM antibodies was < 1% in all groups. Neither the performance
      level of the orienteers nor the place of residence affected the antibody
      prevalence. In conclusion, Swedish orienteers do not show a higher prevalence of
      antibodies to C. pneumoniae than healthy blood donors.

PMID- 11525353
TI  - Bartonella henselae serostatus is not correlated with neurocognitive decline in
      HIV infection.
AB  - Bartonella henselae has been implicated as a significant cause of HIV-associated
      dementia. We attempted to confirm this association by utilizing the database of
      the San Diego HIV Neurobehavioral Research Center, which collects longitudinal
      neurocognitive and laboratory data on over 500 HIV-infected participants.
      Utilizing an immunofluorescent assay we found that 11% of 177 subjects, half of
      whom had documented neurocognitive decline, were seropositive for B. henselae.
      There was no correlation between B. henselae seropositivity and neurocognitive
      decline. The role of B. henselae in HIV-associated dementia remains ambiguous.

PMID- 11525354
TI  - Identification and differentiation of Iranian Leishmania species by PCR
      amplification of kDNA.
AB  - We describe the specific identification of Leishmania species in Iran using PCR
      DNA amplification of kDNA. For this purpose, we designed a pair of primers-
      upstream 5' TCGCAGAACGCCCCTACC 3' and downstream 5'-AGGGGTTGGTGTAAAATAGGC 3'-
      specific for conserved sequences of kDNA of Leishmania. Using this primer, we
      identified 3 different amplified fragments from the kDNA of the WHO reference
      Leishmania species. Two bands at 620 and 850 bp were identified for L. major
      (MRHO/IR/64/Nadim-1 strain) and only 1 band at 620 bp was identified for L. major
      (P strain). Therefore, we could differentiate 2 Leishmania species. Also, 1 band
      at 830 bp was identified for L. tropica (MHOM/Sudan/58/OD strain). We determined
      the sequence analysis of 2 DNA bands (620 and 850 bp) obtained from kDNA of L.
      major (MRHO/IR/64/Nadim-1). A total of 157 bp from the 5' site and 234 bp from
      the 3' site were sequenced and showed about 28% homology between 620 and 850 bp
      fragments. This technique could amplify as little as 1 fg of DNA and was used to
      differentiate kDNA samples isolated from Iranian patients with cutaneous
      leishmaniasis. These data indicate that the primer used for PCR amplification of
      kDNA is specific and can be used for diagnostic and epidemiological purposes.

PMID- 11525355
TI  - Unsuspected extralymphocutaneous dissemination in febrile cat scratch disease.
AB  - Cat scratch disease (CSD) commonly manifests as regional self-limited
      lymphadenitis. However, dissemination of the infection to distant multiple sites
      may occur even in immunocompetent patients. We report a series of 11 children
      with fever and extralymphocutaneous manifestations of CSD, in order to highlight
      potential multiorgan involvement in patients with febrile CSD. To be eligible for
      enrollment, patients had to present with involvement of sites other than regional
      lymph nodes. The diagnosis was based on suggestive clinical criteria,
      histological findings and positive serology. The utilization of ultrasound
      imaging revealed hepatic lesions in 3 children and splenic lesions in 8 children,
      whereas osteolytic lesions were observed in 4 children by bone scan. Hepatic or
      splenic involvement was not suggested by clinical signs or biochemical
      investigation in 2/3 and 6/8 children, respectively. Bone involvement was
      supported either by relative symptoms or signs. Our findings indicate that, in
      the presence of fever, extralymphocutaneous manifestations have to be anticipated
      in patients with clinically suspected CSD. The systematic use of imaging
      modalities in patients with serologically documented Bartonella henselae
      infection could contribute to a better understanding of the clinical spectrum of
      CSD.

PMID- 11525356
TI  - Occurrence and antimicrobial susceptibility of Ureaplasma parvum (Ureaplasma
      urealyticum biovar 1) and Ureaplasma urealyticum (Ureaplasma urealyticum biovar
      2) from patients with adverse pregnancy outcomes and normal pregnant women.
AB  - A recent phylogenetic analysis of Ureaplasma urealyticum resulted in the proposal
      to divide their 2 biovars into species. We used PCR to compare the distribution
      of species and the presence of the tet(M) and int-Tn resistance determinants in
      63 strains of Ureaplasma spp. isolated from the amniotic fluid of patients with
      an adverse pregnancy outcome and in 22 strains obtained from the lower genital
      tract of healthy pregnant women. We also determined the antimicrobial
      susceptibility of the organisms to erythromycin and tetracycline. U. parvum was
      the most frequent Ureaplasma species detected in our study. Thus, 50/63 (79.4%)
      invasive isolates and 17/22 (77.3%) lower genital tract isolates corresponded to
      U. parvum, whereas 12/63 (19%) invasive isolates and 4/22 (18.2%) non-invasive
      strains corresponded to U. urealyticum. A mixture of species was found in 2
      women. We found no significant differences in the antimicrobial susceptibility of
      isolates according to species or origin of isolation. Sixty-two strains of
      Ureaplasma spp. (74.7%) were susceptible to erythromycin, and 21 strains (25.3%)
      were intermediately susceptible. Sixty-eight isolates (81.9%) were susceptible to
      tetracycline, 2 strains (2.4%) were intermediate and 13 strains (15.7%) were
      resistant. DNA sequences related to the tet(M) determinant and the int-Tn gene
      were found in all tetracycline-resistant isolates.

PMID- 11525357
TI  - GB virus C/hepatitis G virus infection in patients investigated for chronic liver
      disease and in the general population in southern Sweden.
AB  - Serum samples from patients referred for liver biopsy for investigation of
      suspected chronic liver disease (n = 286) and from healthy middle-aged volunteers
      (n = 445) were analyzed for markers of exposure to GB virus C/hepatitis G virus
      (GBV-C/HGV), hepatitis B virus and hepatitis C virus. GBV-C/HGV analyses included
      GBV-C/HGV PCR for detection of viremia and GBV-C/HGV enzyme-linked immunosorbent
      assay for anti-GBV-C/HGV E2 antibodies. Liver biopsies were re-evaluated by a
      hepatopathologist. GBV-C/HGV markers were detected in 97/286 (34%) patients (GBV
      C/HGV RNA = 26; anti-GBV-C/HGV E2 antibodies = 74) compared to 86/445 (19%; p <
      0.0001) controls (GBV-C/HGV RNA = 7, anti-GBB-C/HGV E2 antibodies = 79). A
      significantly higher proportion of GBV-C/HGV-exposed subjects in the patient
      group were viremic compared to controls (27% vs. 8.1%; p = 0.0015). GBV-C/HGV
      markers were more commonly found in patients with chronic hepatitis B and C. In
      patients with GBV-C/HGV viremia, a higher occurrence of bile duct degeneration
      was detected than in non-viremic patients. Markers of GBV-C/HGV infection were
      over-represented among patients investigated for chronic liver disease, and
      ongoing GBV-C/HGV viremia was more common in this group than in controls. Apart
      from a higher prevalence of bile duct degeneration in viremic patients, infection
      with GBV-C/HGV did not confer any specific histological characteristics.

PMID- 11525358
TI  - Enhanced immunogenicity of recombinant hepatitis B vaccine in exposed family
      contacts of chronic liver disease patients.
AB  - Close family contacts of hepatitis B virus (HBV)-related chronic liver disease
      patients have a high risk of exposure to HBV. Variable responses to vaccination
      have been reported in family contacts, especially in previously exposed contacts
      (IgG antiHBc-positive). Seventy-nine healthy family contacts, who were HBsAg
      negative with normal alanine amino-transferase level and no evidence of liver
      disease, were vaccinated using a recombinant HBV vaccine, irrespective of past
      exposure status. A significantly higher number of previously exposed subjects (n
      = 25; Group I) developed early seroprotective anti-HBs titers with 2 initial
      doses of vaccine compared to the unexposed contacts (Group II; n = 54) (64% vs.
      33%, respectively; P < 0.05). However, the responses were comparable on
      completion of the schedule (96% vs. 94%, respectively). HBV DNA was detected in
      11 of 25 (44%) exposed and none of the unexposed contacts at baseline. Post
      vaccination, 3 of 11 (27%) subjects became HBV DNA-negative and remained negative
      for the next 12 months. These results suggest that exposed family contacts
      achieve efficient seroprotection after HBV vaccination, irrespective of the IgG
      anti-HBc status. The response to vaccination resembles an anamnestic reaction and
      possibly demonstrates a therapeutic effect.

PMID- 11525359
TI  - Sudden death in Staphylococcus aureus-associated infective endocarditis due to
      perforation of a free-wall myocardial abscess.
AB  - Free-wall myocardial abscess perforation with hemopericardium and sudden death is
      an extremely infrequent complication of infective endocarditis (IE). We describe
      a case of Staphylococcus aureus-associated native aortic and tricuspid valve
      endocarditis complicated by a septic myocardial infarction and abscess formation
      of embolic origin, with fatal rupture into the pericardium. To our knowledge,
      only 2 cases of myocardial abscess rupture have previously been reported in
      relation to IE.

PMID- 11525360
TI  - Clinical "pneumococcal pneumonia" due to Moraxella osloensis: case report and a
      review.
AB  - A previously healthy 6-y-old girl presented with a disease very similar to
      pneumococcal pneumonia. However, Moraxella osloensis was isolated by lung tap.
      The patient responded well to a course of parenteral penicillin. This is probably
      the first documented case of community-acquired pneumonia associated with this
      agent. Clinical isolates of M. osloensis are rare and its pathogenesis has not
      been delineated; however, a literature review suggests that the organism is more
      common than is generally recognized.

PMID- 11525361
TI  - Central venous catheter-related infection due to Comamonas testosteroni in a
      woman with breast cancer.
AB  - A 75-y-old woman with breast cancer presented with bacteremia due to Comamonas
      testosteroni. Evolution was favorable following adapted antimicrobial therapy and
      removal of a central venous catheter. This germ seems to be a rare pathogen; as
      reported in the literature, it is mostly encountered in patients with
      predisposing factors.

PMID- 11525362
TI  - Non-clostridial gas gangrene caused by Klebsiella pneumoniae: a case report.
AB  - A 45-y-old man was hospitalized due to pain and swelling of the right leg for 3
      d. Bullae developed with gas formation involving multiple compartments of the
      entire limb 46 h later. Klebsiella pneumoniae was recovered from blood and
      surgical specimens. The patient died on Day 8 despite amputation and antibiotic
      therapy.

PMID- 11525363
TI  - Polio vaccine virus-associated meningoencephalitis in an infant with transient
      hypogammaglobulinemia.
AB  - The case of an infant with transient hypogammaglobulinemia who developed
      meningoencephalitis, retinitis and sensorineural hearing loss is presented. The
      neurovirulent variant of the Sabin type 2 oral poliovirus vaccine was detected in
      cerebrospinal fluid and stool.

PMID- 11525364
TI  - Measles-associated appendicitis: two case reports and literature review.
AB  - We report 2 cases of appendicitis associated with measles. Four previously
      reported cases are reviewed. In all 6 patients typical measles rash appeared
      after removal of the appendix, which showed Warthin-Finkelday giant cells.

PMID- 11525365
TI  - Culture-negative severe septic shock: indications for streptococcal aetiology
      based on plasma antibodies and superantigenic activity.
AB  - We present a severe septic shock syndrome patient with negative blood cultures.
      Acute and convalescent plasma samples from the patient were analysed for anti
      streptolysin O titres, superantigen-neutralizing activity and presence of
      superantigenic activity. The plasma analyses implicated superantigen-producing
      Streptococcus pyogenes as the causative agent.

PMID- 11525366
TI  - Laparoscopic adjustable silicone gastric banding: prospective evaluation of
      intragastric migration of the lap-band.
AB  - Intragastric prosthesis (Lap-Band, BioEnterics Co., Carpinteria, CA, U.S.A.)
      migration is one of the major long-term complications of laparoscopic adjustable
      silicone gastric banding. The causes, clinical signs, timing, and overall
      incidence of band entrapment have not been prospectively investigated in a large
      series. The purpose of this study was to assess prospectively the incidence of
      Lap-Band intragastric migration and to establish the safety and effectiveness of
      minimally invasive band removal. Between January 1996 and June 2000, 148
      consecutive patients enrolled in a multidisciplinary bariatric program underwent
      laparoscopic adjustable silicone gastric banding. In the follow-up treatment,
      gastrointestinal endoscopy was performed routinely. One hundred twenty-three
      patients with a minimum follow-up period of 12 months were entered into the study
      group. Eleven (9.2%) patients had long-term major complications. Intragastric
      band migration was observed in nine (7.5%) patients. The diagnosis was
      established by routine endoscopy between 10 and 41 months after surgery. Five
      erosions occurred in the first 30 cases (learning curve period). In six patients,
      the band was removed by an intragastric endoscopic-assisted approach avoiding
      laparotomy. The remaining three patients are under endoscopic surveillance. The
      results of this study show that routine upper gastrointestinal endoscopy can
      discover asymptomatic band migrations early. Band erosion did not require
      emergency treatment and can be removed safely by a minimally invasive approach.

PMID- 11525367
TI  - A postfundoplication study on Z-line appearance and intestinal metaplasia in the
      gastroesophageal junction.
AB  - The purpose of this study was investigate the Z-line appearance by using a
      previously proposed classification, the ZAP classification, and to investigate
      the prevalence of intestinal metaplasia in the Z-line, among fundoplicated
      patients. Sixty patients, who had undergone fundoplication 2 to 17 years earlier,
      were included in the study. The prevalence of intestinal metaplasia was 20%.
      Intestinal metaplasia was found to be associated with age, more than 10 years of
      symptoms of gastroesophageal reflux disease preoperatively, tongues of columnar
      epithelium in the distal esophagus, carditis, and ZAP grade. ZAP grade,
      furthermore, was associated with male gender and more than 10 years of symptoms
      of gastroesophageal reflux disease preoperatively. Among patients with intestinal
      metaplasia, different ZAP grades can indicate different etiologic factors. Even
      among patients undergoing fundoplication (i.e., patients with an anatomically
      altered gastroesophageal junction), the ZAP classification is a feasible tool to
      characterize the Z-line appearance. The ZAP classification could prove valuable
      in selecting patients for follow-up treatment.

PMID- 11525368
TI  - Role of laparoscopic cholecystectomy in the management of polypoid lesions of the
      gallbladder.
AB  - This retrospective clinicohistopathologic study was performed to delineate the
      role of laparoscopic cholecystectomy in the management of polypoid lesions of the
      gallbladder. One hundred forty-three consecutive patients who had a preoperative
      sonographic diagnosis of polypoid lesions of the gallbladder with a diameter less
      than 1.5 cm and who underwent laparoscopic cholecystectomy at Cathay General
      Hospital were included in the analysis. Histopathologic study showed that 22
      (15.4%) patients had true tumors, including adenoma (16), adenoma with focal
      adenocarcinoma (2), adenocarcinoma (3), and carcinoid tumor (1). Tumorlike
      lesions were found in 121 (84.6%) patients and included cholesterol polyp (106),
      adenomyomatous hyperplasia (10), inflammatory polyp (3), and papillary
      hyperplasia (2). The mean diameter of malignant polypoid lesions of the
      gallbladder was 1.35 +/- 0.42 cm, which was significantly larger than that of
      cholesterol polyps (0.66 +/- 0.40 cm, P = 0.0001) but not significantly larger
      than that of adenomyomatous hyperplasias (1.12 +/- 0.42 cm) and adenomas (1.08 +/
      0.47 cm). The mean age of patients with malignant polypoid lesions of the
      gallbladder (61.2 +/- 13.3 years old) was significantly older than that of
      patients with adenomyomatous hyperplasia (46.6 +/- 13.4 years, P = 0.03),
      cholesterol polyps (44.5 +/- 10.5 years, P = 0.0003), and adenomas (41.4 +/- 9.4
      years, P = 0.0008). Clinical follow-up showed that most (98.6%) patients
      benefited from the minimal invasiveness of laparoscopic cholecystectomy with
      satisfactory surgical results. We conclude that laparoscopic cholecystectomy is a
      reliable, safe, and minimally invasive biopsy procedure and definite management
      of polypoid lesions of the gallbladder with a diameter less than 1.5 cm.

PMID- 11525369
TI  - Two-trocar laparoscopic cholecystectomy: a reproducible technique.
AB  - Laparoscopic cholecystectomy is usually performed with a four-trocar technique.
      From December 1998 to March 1999, 25 of 42 admitted patients underwent a two
      trocar laparoscopic cholecystectomy. In our technique, after establishing
      umbilical carbon dioxide pneumoperitoneum, a 30 degree scope was inserted, and a
      second 5-mm trocar was positioned below and to the left of the xiphoid process.
      Then two stitches with nonabsorbable sutures were passed: one at the fundus to
      pull up the gallbladder, and the second through the neck of the gallbladder to
      expose the structure of the Calot triangle. Intraoperative cholangiography was
      performed with a percutaneous catheter in 15 patients. Retrograde cholecystectomy
      was performed and the gallbladder was extracted through the umbilical port. Scars
      were closed with glue, and bupivacaine was injected to reduce pain. The technique
      was feasible in approximately 84% (25 of 30) of patients. The mean operative time
      was 42 minutes, and the mean hospital stay was 1.6 days. We conclude that this
      method is similar to four-port laparoscopic cholecystectomy in terms of safety
      and operation time. This technique seems to be well reproducible and offers
      better results in terms of postoperative pain, hospital stay without considering
      better cosmetic results, and cost-effectiveness.

PMID- 11525370
TI  - Laparoscopic versus open cholecystectomy: a prospective comparative study in the
      elderly with acute cholecystitis.
AB  - The aim of this prospective comparative study was to determine the feasibility
      and the efficacy of laparoscopic cholecystectomy for acute cholecystitis in
      patients older than 75 years of age and to compare the results with those of open
      cholecystectomy. From January 1992 to December 1999, 139 patients older than 75
      years of age underwent cholecystectomy for acute cholecystitis. The two groups of
      patients with cholecystolithiasis included 50 patients who underwent laparoscopic
      cholecystectomy (group 1) and 89 patients who underwent open cholecystectomy
      (group 2). Group 1 consisted of 30 women and 20 men, with a mean age of 81.9
      years (range, 75-98). Group 2 consisted of 51 women and 38 men, with a mean age
      of 81.9 years (range, 75-93). There was no difference in the American Society of
      Anesthesiologists classification in both groups. The length of the surgery (103.3
      vs. 149.7 minutes), postoperative length of stay (7.7 vs. 12.7 days), and
      inpatient rehabilitation (15 vs. 42 patients) were significantly shorter in group
      1 than in group 2. The postoperative morbidity rate was not different between the
      groups. There was no mortality in group 1, but four patients died in group 2 (P =
      0.29). The conversion rate was 32% (n = 16) in group 1. In summary, laparoscopic
      cholecystectomy in elderly patients with acute cholecystitis is safe and
      effective. Laparoscopic cholecystectomy in elderly patients restores them to the
      best possible quality of life with the lowest cost to them physiologically.

PMID- 11525371
TI  - Results of laparoscopic and open splenectomy for nontraumatic diseases.
AB  - The medical records of patients who had undergone splenectomy for nontraumatic
      diseases of the spleen between 1997 and 2000 were reviewed. The aim of the study
      was to evaluate the short-term outcomes of open and laparoscopic splenectomies
      and to determine whether some well-known benefits of laparoscopic surgery could
      be observed in patients who underwent laparoscopic splenectomy for nontraumatic
      splenic diseases. The data of 44 patients were available for analysis and
      included 20 patients (45.5%) who underwent laparoscopic splenectomy and 24
      patients (54.5%) who underwent open splenectomy. Various parameters were reported
      for open and laparoscopic procedures separately, including associated surgical
      procedures, spleen weight, postoperative mortality and morbidity rates,
      perioperative blood transfusions, use and length of abdominal drainage, accessory
      spleen removal, operative times, length of hospital recovery, and hematologic
      parameters on admission to and discharge from the hospital. Laparoscopic
      splenectomy was successfully completed in all 20 considered patients with no
      conversion to open splenectomy. The supine position and four trocars were adopted
      in all patients. Accessory spleens were found in four (9.0%) patients: two (4.5%)
      during open splenectomy and two (4.5%) during laparoscopic splenectomy. The
      postoperative mortality rate was 2.7% (a case of myocardial infarction). The
      morbidity rate was 9% (four patients), but no postoperative complications
      occurred after laparoscopic splenectomy. A significant statistical difference was
      shown by the increase in platelet counts after open versus laparoscopic
      splenectomy. The open and laparoscopic mean operative times (73.70 +/- 13.42
      minutes and 78.42 +/- 14.63 minutes, respectively) were comparable. These times
      were comparable also considering patients who underwent only splenectomy. Mean
      recovery time was shorter after laparoscopic splenectomy (3.95 +/- 0.60 days)
      than after open splenectomy (7.0 +/- 1.68 days). After open procedures, however,
      the mean recovery time was shorter in uncomplicated cases (6.68 +/- 1.49 days)
      than in the open group as a whole. Authors conclude that many well-known
      advantages of the laparoscopic approach. especially those related to its low
      invasiveness, can be observed in patients requesting splenectomy for nontraumatic
      diseases of the spleen, without lowering the efficacy of this operation. They
      suggest that such advantages can be entirely displayed when selection criteria of
      the patients are applied.

PMID- 11525372
TI  - Simultaneous repair of bilateral inguinal hernias: a prospective, randomized
      study of open, tension-free versus laparoscopic approach.
AB  - No randomized trial exists that specifically addresses the issue of laparoscopic
      bilateral inguinal hernia repair. The purpose of the present prospective,
      randomized, controlled, clinical study was to assess short- and long-term results
      when comparing simultaneous bilateral hernia repair by an open, tension-free
      anterior approach with laparoscopic "bikini mesh" posterior repair. Forty-three
      low-risk male patients with bilateral primary inguinal hernia were randomly
      assigned to undergo either laparoscopic preperitoneal "bikini mesh" hernia repair
      (TAPP) or open Lichtenstein hernioplasty. There was no difference in operating
      time between the two groups. The mean cost of laparoscopic hernioplasty was
      higher (P < 0.001). The intensity of postoperative pain was greater in the open
      hernia repair group at 24 hours, 48 hours, and 7 days after surgery (P < 0.001),
      with a greater consumption of pain medication among these patients (P < 0.05).
      The median time to return to work was 30 days for the open hernia repair group
      and 16 days for the laparoscopic "bikini mesh" repair group (P < 0.05). Only 1
      asymptomatic recurrence (4.3%) was discovered in the open group. The laparoscopic
      approach to bilateral hernia with "bikini mesh" appears to be preferable to the
      open Lichtenstein tension-free hernioplasty in terms of the postoperative quality
      of life and interruption of occupational activity.

PMID- 11525373
TI  - A clinical analysis of gasless endoscopic thyroidectomy.
AB  - Gasless endoscopic surgery was applied to a thyroidectomy. Compared with the
      previous method of endoscopic thyroidectomy, this method is superior in obtaining
      hemostasis and minimizing the possible complications of gas-insufflating surgery,
      such as a hypercapnia or massive subcutaneous emphysema. We successfully removed
      37 thyroid tumors in 35 patients by gasless endoscopic surgery without any
      significant complications. No scars remained in the neck, and all patients were
      satisfied with the cosmetic results. Gasless endoscopic thyroidectomy is a safe
      and technically feasible alternative to conventional thyroidectomy for cases of
      benign thyroid tumors and has good cosmetic results.

PMID- 11525374
TI  - Thoracoscopic resection of an esophageal stromal tumor through the left pleural
      cavity.
AB  - We describe the technique for endoscopic removal of a stromal tumor of the lower
      third of the esophagus through the left thoracoscopic approach. The tumor
      resembled a leiomyoma and was classified as a borderline, potentially malignant
      lesion after thoracoscopic removal. The technique and clinical implications in
      such cases are discussed on the basis of current knowledge.

PMID- 11525375
TI  - Cholecystogastric fistula: laparoscopic repair.
AB  - We describe a patient with a cholecystogastric fistula treated by the
      laparoscopic approach. The use of intracorporeal suturing allows laparoscopic
      management of cholecystogastric fistulae without the need for an endoscopic
      transecting stapler.

PMID- 11525376
TI  - Laparoscopic enucleation of insulinoma in the pancreas: case report and review of
      the literature.
AB  - We report a case of islet cell tumor of the pancreas managed by laparoscopic
      surgery. A 27-year-old woman was admitted to the hospital after fainting from
      hypoglycemia. Diagnostic imaging showed a small tumor 1 cm in diameter in the
      body of the pancreas. Laparoscopic enucleation of the tumor was performed with
      laparoscopic coagulating shears. The operation time was 210 minutes, and there
      were no perioperative complications such as pancreatic leakage. The postoperative
      course was uneventful, and the patient was discharged from the hospital on the
      seventh postoperative day. The histopathologic diagnosis was insulin-producing
      islet cell tumor. This method is technically feasible and safe for the management
      of small islet cell tumors located on the surface of the pancreas.

PMID- 11525377
TI  - Laparoscopic appendectomy in children with Enterobius vermicularis.
AB  - As surgeons gain more experience with laparoscopy in children, it is becoming
      apparent that one of the best applications of the technique is for appendicitis.
      The advantages of laparoscopic appendectomy include a better cosmetic result,
      particularly in young female patients, a shorter recovery time, and an early
      return to normal activities. In the differential diagnosis of appendicitis, the
      association of Enterobius vermicularis (pinworms) inflammation in the pediatric
      age group is not uncommon. The endo-loop technique for laparoscopic appendectomy
      is the standard technique used in our department. In three patients with E.
      vermicularis undergoing appendix removal using this technique, pinworms were
      found to be set free into the abdomen after dividing the appendix between the
      loop ligatures. Bipolar coagulating forceps were used carefully to thermally
      desiccate the worms, which were then removed using a blunt grasper. E.
      vermicularis being released into the abdomen in children undergoing laparoscopic
      appendectomy using the endo-loop technique has not been reported. Careful
      evaluation of the appendix stump and simple but careful thermal desiccation and
      removal of pinworms, if present, must be considered when using the endo-loop
      technique.

PMID- 11525378
TI  - Laparoscopy-assisted resection for jejunal carcinoma.
AB  - Laparoscopic surgery has been applied in small bowel resections for various
      diseases, such as obstruction including intussusception, diverticula, and tumors.
      We report a case of successful resection of a jejunal carcinoma that was
      diagnosed before surgery by using a laparoscopy-assisted technique.

PMID- 11525379
TI  - Emergency replacement for damaged balloon dissector for laparoscopic
      extraperitoneal inguinal hernia repair.
AB  - The purpose of this study was to find an effective and reasonable solution to
      replace damaged balloon dissector used in laparoscopic extraperitoneal inguinal
      hernia repair. The thumb of a surgical glove was used to repair torn balloon
      dissector for laparoscopic total extraperitoneal hernia repair. The new balloon
      presented an adequate tightness to perform the dissection of the extraperitoneal
      area without complication. Although the best way to replace a damaged balloon
      dissector is to replace it with a new one, this method may be taken into
      consideration in such a situation in which a new balloon dissector is not
      available.

PMID- 11525380
TI  - The molecular biology of the group VIA Ca2+-independent phospholipase A2.
AB  - The group VIA PLA2 is a member of the PLA2 superfamily. This enzyme, which is
      cytosolic and Ca2+-independent, has been designated iPLA2beta to distinguish it
      from another recently cloned Ca2+-independent PLA2. Features of iPLA2beta
      molecular structure offer some insight into possible cellular functions of the
      enzyme. At least two catalytically active iPLA2beta isoforms and
      additionalsplicing variants are derived from a single gene that consists of at
      least 17 exons located on human chromosome 22q13.1. Potential tumor suppressor
      genes also reside at or near this locus. Structural analyses reveal that
      iPLA2beta contains unique structural features that include a serine lipase
      consensus motif (GXSXG), a putative ATP-binding domain, an ankyrin-repeat domain,
      a caspase-3 cleavage motif DVTD138Y/N, a bipartite nuclear localization signal
      sequence, and a proline-rich region in the human long isoform. iPLA2beta is
      widely expressed among mammalian tissues, with highest expression in testis and
      brain. iPLA2beta prefers to hydrolyze fatty acid at the sn-2 fatty acid
      substituent but also exhibits phospholipase A1, lysophospholipase, PAF
      acetylhydrolase, and transacylase activities. iPLA2beta may participate in
      signaling, apoptosis, membrane phospholipid remodeling, membrane homeostasis,
      arachidonate release, and exocytotic membrane fusion. Structural features and the
      existence of multiple splicing variants of iPLA2beta suggest that iPLA2beta may
      be subject to complex regulatory mechanisms that differ among cell types. Further
      study of its regulation and interaction with other proteins may yield insight
      into how its structural features are related to its function.

PMID- 11525381
TI  - Molecular and cellular biology of the human reduced folate carrier.
AB  - The natural folates are water-soluble members of the B class of vitamins that are
      essential for cell proliferation and tissue regeneration. Since mammalian cells
      cannot synthesize folates de novo, tightly regulated and sophisticated cellular
      uptake processes have evolved to sustain sufficient levels of intracellular
      tetrahydrofolate cofactors to support the biosynthesis of purines, pyrimidines,
      serine, and methione. Membrane transport is also a critical determinant of the
      antitumor activity of antifolate therapeutics (methotrexate, Tomudex) used in
      cancer chemotherapy, and impaired uptake of antifolates is a frequent mode of
      drug resistance. The reduced folate carrier is the major transport system for
      folates and classical antifolates in mammalian cells and tissues. This review
      summarizes the remarkable advances in the cellular and molecular biology of the
      human reduced folate carrier over the past decade, relating to its molecular
      structure and transport function, mechanisms of transcriptional and
      posttranscriptional regulation, and its critical role in antifolate response and
      resistance. Many key in vitro findings have now begun to be extended to studies
      of reduced folate carrier levels and function in patient specimens, paving the
      way for translating basic laboratory studies in cultured cells to improvements in
      human health and treatment of disease. The results of research into the human
      reduced folate carrier should clarify the roles of changes in expression and
      function of this system that accompany nutritional folate deficiency and human
      disease, and may lead to improved therapeutic strategies for enhancing drug
      response and circumventing resistance in cancer patients undergoing chemotherapy
      with antifolates.

PMID- 11525382
TI  - Gene targeting via triple-helix formation.
AB  - A report on a recent workshop entitled "Gene-Targeted Drugs: Function and
      Delivery" conveys a justified optimism for the eventual feasibility and
      therapeutic benefit of gene-targeting strategies. Although multiple approaches
      are being explored, this chapter focuses primarily on the uses of triplex-forming
      oligonucleotides (TFOs). TFOs are molecules that bind in the major groove of
      duplex DNA and by so doing can produce triplex structures. They bind to the
      purine-rich strand of the duplex through Hoogsteen or reverse Hoogsteen hydrogen
      bonding. They exist in two sequence motifs, either pyrimidine or purine.
      Improvements in delivery of these TFOs are reducing the quantities required for
      an effective intracellular concentration. New TFO chemistries are increasing the
      half-life of these oligos and expanding the range of sequences that can be
      targeted. Alone or conjugated to active molecules, TFOs have proven to be
      versatile agents both in vitro and in vivo. Foremost, TFOs have been employed in
      antigene strategies as an alternative to antisense technology. Conversely, they
      are also being investigated as possible upregulators of transcription. TFOs have
      also been shown to produce mutagenic events, even in the absence of tethered
      mutagens. TFOs can increase rates of recombination between homologous sequences
      in close proximity. Directed sequence changes leading to gene correction have
      been achieved through the use of TFOs. Because it is theorized that these
      modifications are due to the instigation of DNA repair mechanisms, an important
      area of TFO research is the study of triple-helix recognition and repair.

PMID- 11525383
TI  - Searching new targets for anticancer drug design: the families of Ras and Rho
      GTPases and their effectors.
AB  - The Ras superfamily of low-molecular-weight GTPases are proteins that, in
      response to diverse stimuli, control key cellular processes such as cell growth
      and development, apoptosis, lipid metabolism, cytoarchitecture, membrane
      trafficking, and transcriptional regulation. More than 100 genes of this
      superfamily grouped in six subfamilies have been described so far, pointing to
      the complexities and specificities of their cellular functions. Dysregulation of
      members of at least two of these families (the Ras and the Rho families) is
      involved in the events that lead to the uncontrolled proliferation and
      invasiveness of human tumors. In recent years, the cloning and characterization
      of downstream effectors for Ras and Rho proteins have given crucial clues to the
      specific pathways that lead to aberrant cellular growth and ultimately to
      tumorigenesis. A direct link between the functions of some of these effectors
      with the appearance of transformed cells and their ability to proliferate and
      invade surrounding tissues has been made. Accordingly, drugs that specifically
      alter their functions display antineoplasic properties, and some of these drugs
      are already under clinical trials. In this review, we survey the progress made in
      understanding the underlying molecular connections between carcinogenesis and the
      specific cellular functions elicited by some of these effectors. We also discuss
      new drugs with antineoplastic or antimetastatic activity that are targeted to
      specific effectors for Ras or Rho proteins.

PMID- 11525384
TI  - Major histocompatibility class I folding, assembly, and degradation: a paradigm
      for two-stage quality control in the endoplasmic reticulum.
AB  - Protein folding in living cells is a complex process involving many
      interdependent factors. The primary site for folding of nascent proteins destined
      for secretion is the endoplasmic reticulum (ER). Several disease states,
      including cystic fibrosis, are brought about because of irregularities in protein
      folding. Under normal cellular conditions, "quality control" mechanisms ensure
      that only correctly folded proteins are exported from the ER, with incorrectly
      folded or incompletely assembled proteins being degraded. Quality control
      mechanisms can be divided into two broad processes: (1) Primary quality control
      involves general mechanisms that are not specific for individual proteins; these
      monitor the fidelity of nascent protein folding in the ER and mediate the
      destruction of incompletely folded proteins. (2) Partially folded or assembled
      proteins may be subject to secondary quality control mechanisms that are protein-
      or protein-family-specific. Here we use the folding and assembly of major
      histocompatibility complex (MHC) class I as an example to illustrate the
      processes of quality control in the ER. MHC class I, a trimeric complex assembled
      in the ER of virally infected or malignant cells, presents antigenic peptide to
      cytotoxic T lymphocytes; this mediates cell killing and thereby prevents the
      spread of infection or malignancy. The folding and assembly of MHC class I is
      subjected to both primary and secondary quality control mechanisms that lead
      either to correct folding, assembly, and secretion or to degradation via a
      proteasome-associated mechanism.

PMID- 11525385
TI  - CooA: a heme-containing regulatory protein that serves as a specific sensor of
      both carbon monoxide and redox state.
AB  - CooA, the heme-containing carbon monoxide (CO) sensor from the bacterium
      Rhodospirillum rubrum, is a transcriptional factor that activates expression of
      certain genes in response to CO. As with other heme proteins, CooA is unable to
      bind CO when the Fe heme is oxidized, consistent with the fact that some of the
      regulated gene products are oxygen-labile. Upon reduction, there is an unusual
      switch of protein ligands to the six-coordinate heme and the reduced heme is able
      to bind CO. CO binding stabilizes a conformation of the dimeric protein that
      allows sequence-specific DNA binding, and transcription is activated through
      contacts between CooA and RNA polymerase. CooA is therefore a novel redox sensor
      as well as a specific CO sensor. CooA is a homolog of catabolite responsive
      protein (CRP), whose transcriptionally active conformation has been known for
      some time. The recent solution of the crystal structure of the CO-free
      (transcriptionally inactive) form of CooA has allowed insights into the mechanism
      by which both proteins respond to their specific small-molecule effectors.

PMID- 11525386
TI  - The msDNAs of bacteria.
AB  - msDNAs are small, structurally unique satellite DNAs found in a number of Gram
      negative bacteria. Composed of hundreds of copies of single-stranded DNA--hence
      the name multicopy single-stranded DNA--msDNA is actually a complex of DNA, RNA,
      and probably protein. These peculiar molecules are synthesized by a reverse
      transcription mechanism catalyzed by a reverse transcriptase (RT) that is
      evolutionarily related to the polymerase found in the HIV virus. The genes,
      including the RT gene, responsible for the synthesis of msDNA are encoded in a
      retron, a genetic element that is carried on the bacterial chromosome. The retron
      is, in fact, the first such retroelement to be discovered in prokaryotic cells.
      This report is a comprehensive review of the many interesting questions raised by
      this unique DNA and the fascinating answers it has revealed. We have learned a
      great deal about the structure of msDNA: how it is synthesized, the structure and
      functions of the RT protein required to make it, its effects on the host cell,
      the retron element that encodes it, its possible origins and evolution, and even
      its potential usefulness as a practical genetic tool. Despite the impressive
      gains in our understanding of the msDNAs, however, the simple, fundamental
      question of its natural function remains an enduring mystery. Thus, we have much
      more to learn about the msDNAs of bacteria.

PMID- 11525387
TI  - Cisplatin: from DNA damage to cancer chemotherapy.
AB  - Cisplatin [cis-DDP, cis-diamminedichloroplatinum(II)] is a potent anticancer drug
      that has been used successfully to treat tumors of the head, neck, lungs, and
      genitourinary tract. The biological activity of cisplatin was discovered
      serendipitously more than 30 years ago, and since that time research efforts have
      focused on elucidating its mechanism of action. The present review provides a
      historical perspective of our attempts to understand this complex phenomenon and
      the results of recent work that guides our current activities in this field.
      Continued efforts to understand the mechanism of genotoxicity of cisplatin are
      expected to lead to the discovery of new drugs and combinations for the
      improvement of cancer chemotherapy.

PMID- 11525388
TI  - HIV/AIDS in Europe: the challenge for health promotion research.

PMID- 11525389
TI  - Community-based HIV/AIDS education in rural Uganda: which channel is most
      effective?
AB  - A process evaluation was conducted to evaluate four channels (drama, video,
      community educators and leaflets) used in a community-based IEC (Information,
      Education and Communication) HIV/AIDS intervention in rural Uganda. Semi
      structured interviews (n = 37) and focus groups (n = 3) were held with community
      members working as field staff. In addition, two questionnaire surveys (n = 105
      and n = 69) and eight focus groups were conducted with the target community. Over
      85% of the community had seen at least one drama or video show. They rated them
      as relevant and realistic. However, the messages 'taken home' were not always
      those intended by the plays. Access to community educators (CEs) was not equal.
      The CEs had a tendency to avoid the educated, rich and their older relatives.
      Those who had met with a CE rated them as knowledgeable and trustworthy, but felt
      they would rather be taught by a trained health worker. Around 80% of the
      community said they had seen the leaflets, but had not necessarily read them.
      Although appreciated by some as reference material, low literacy levels and a
      lack of reading culture meant that some leaflets may have gone astray. These
      findings suggest that a multi-channel approach may be required to overcome
      weaknesses inherent in individual channels.

PMID- 11525390
TI  - Determinants of implementing heart health: promotion activities in Ontario public
      health units: a social ecological perspective.
AB  - This paper reports the results of a study undertaken to explain levels of
      implementation of heart health promotion activities observed in Ontario public
      health agencies in 1997. Organizational-level data were collected by surveying
      all 42 health departments in 1994, 1996 and 1997 as part of the Canadian Heart
      Health Initiative Ontario Project. Guided by social ecological and organizational
      theories, the model examines relationships between implementation and four sets
      of possible determinants of activity: (1) the predisposition of agencies to
      undertake heart health promotion activities, (2) their capacity to undertake
      these activities, (3) internal organizational factors and (4) external system
      factors. A small set of five variables explains almost half of the variance in
      implementation (R2 = 0.46): organizational capacity (beta = 0.40), priority given
      to heart health (beta = 0.36), coordination of programs (beta = 0.19), use of
      resource centers (beta = 0.12) and participation in networks (beta = 0.09). The
      results suggest that models integrating organizational and socio-ecological
      theories can help us understand the implementation of community-based heart
      health promotion activities by public health agencies. Implications for future
      research, policy and practice are discussed.

PMID- 11525391
TI  - Food likes and their relative importance in human eating behavior: review and
      preliminary suggestions for health promotion.
AB  - The present article reviews research about the psychological determinants of
      human eating behavior. A hypothetical model of food choice and intake is
      introduced, presenting various factors influencing eating behavior. Internal
      factors include sensory food aspects. Among the external factors are information,
      the social context and the physical environment. Processes such as mere exposure,
      Pavlovian conditioning and social learning shape the relationships between these
      factors, food liking and eating behavior. The relative contribution of the
      various determinants is discussed. In spite of a scarcity of studies, liking for
      the sensory aspects of food seems to be at the center of the development,
      maintenance and change of dietary patterns. Consequently, efforts for promoting
      healthy eating behavior might benefit from an increased attention towards
      learning principles and food likes in the development of interventions. Existing
      intervention strategies are criticized and preliminary suggestions are formulated
      to enhance their effectiveness.

PMID- 11525392
TI  - Understanding reasons for drug use amongst young people: a functional
      perspective.
AB  - This study uses a functional perspective to examine the reasons young people cite
      for using psychoactive substances. The study sample comprised 364 young poly-drug
      users recruited using snowball-sampling methods. Data on life-time and recent
      frequency and intensity of use for alcohol, cannabis, amphetamines, ecstasy, LSD
      and cocaine are presented. A majority of the participants had used at least one
      of these six drugs to fulfil 11 of 18 measured substance use functions. The most
      popular functions for use were using to: relax (96.7%), become intoxicated
      (96.4%), keep awake at night while socializing (95.9%), enhance an activity
      (88.5%) and alleviate depressed mood (86.8%). Substance use functions were found
      to differ by age and gender. Recognition of the functions fulfilled by substance
      use should help health educators and prevention strategists to make health
      messages about drugs more relevant and appropriate to general and specific
      audiences. Targeting substances that are perceived to fulfil similar functions
      and addressing issues concerning the substitution of one substance for another
      may also strengthen education and prevention efforts.

PMID- 11525393
TI  - Rattling the plate--reasons and rationales for early weaning.
AB  - To identify a range of attitudes and beliefs which influence the timing of
      introduction to solid food, five focus group discussions were undertaken within a
      maternity hospital setting. These sessions explored early feeding behaviour,
      stimuli to changing feeding habits and subsequent responses in 22 primiparous and
      seven multiparous mothers (mean age 27.0+/-4.8 years) with babies aged 8-18 weeks
      (mean age 13.0+/-4.2 weeks). One-third of the participants had introduced solid
      food to their infants (mean age of introduction 11.6 weeks, range 2-16 weeks).
      Mothers believed that the introduction of solids was baby led and initiated by
      some physical characteristic or behavioural action of the infant. All mothers
      were aware of current recommendations to avoid the introduction of solid food
      until 4 months. Few knew why this should be and concepts of long-term ill health
      were difficult to conceptualize. The conflict between rigid feeding guidelines
      and flexible advice from supportive health professionals created confusion over
      the importance of good weaning practices. The current findings highlight issues
      relevant to the introduction of solid food, and provide a foundation for further
      research which can identify the relative importance of these factors and provide
      a rationale for the design of contemporary intervention strategies.

PMID- 11525394
TI  - A comparative study of peer-led and adult-led school sex education.
AB  - There are, and have been, many school-based sex education projects in this
      country which have used peer leaders (students delivering an educational
      programme who are of similar, or slightly older, age than the students receiving
      the programme). Rigorous evaluation of the methodology remains scant. This paper
      describes a comparative investigation of peer-led and adult-led sex education in
      National Curriculum Year 9 (aged 13/14 years). The results from this study
      suggest that peer leaders appear to be more effective in establishing
      conservative norms and attitudes related to sexual behaviour than the adults.
      Peer leaders were less effective than adults in imparting factual information and
      getting students involved in classroom activities. These findings suggest that
      both adult-led and peer-led methods may have a place in effective sex education-
      the challenge being to determine which areas are best dealt with by whom.

PMID- 11525396
TI  - Response to Kreuter and Skinner: consensus regarding use of the terms targeting
      and tailoring.

PMID- 11525395
TI  - Impact of health education on knowledge and prevention behavior for congenital
      toxoplasmosis: the experience in Poznan, Poland.
AB  - In 1991-1997 educational activities were undertaken in the Poznan region of
      Poland to promote health education for the prevention of toxoplasmosis. The
      effect of education was measured in 2710 pregnant women by a questionnaire
      survey. Knowledge of toxoplasmosis and its prevention was almost doubled within 4
      years. Similarly, the proportion of women having antenatal serological tests for
      toxoplasmosis significantly increased. In the examined population the knowledge
      of how Toxoplasma gondii is transmitted/acquired was better than the knowledge of
      individual risk factors for congenital toxoplasmosis. Correct hygienic behaviors
      in pregnancy were often practised by women who lacked good knowledge of
      toxoplasmosis. The experience from this study suggests the possible effectiveness
      of including prevention of toxoplasmosis into the whole package of preventing
      infectious diseases in pregnancy and into healthy lifestyle promotion. Health
      educational activities need to be realized by modern promotional technologies in
      addition to making available traditional written educational texts. There is a
      considerable role of medical services in promotion of a hygienic behavior in
      pregnant women preventing congenital toxoplasmosis in their offspring. Health
      education should be especially tailored to the population of pregnant women below
      the age of 21.

PMID- 11525397
TI  - International governance and reform of the World Trade Organization.

PMID- 11525398
TI  - Community-campus partnerships for health.

PMID- 11525399
TI  - The Saccharomyces cerevisiae aldose reductase is implied in the metabolism of
      methylglyoxal in response to stress conditions.
AB  - The enzyme aldose reductase plays an important role in the osmo-protection
      mechanism of diverse organisms. Here, we show that yeast aldose reductase is
      encoded by the GRE3 gene. Expression of GRE3 is carbon-source independent and up
      regulated by different stress conditions, such as NaCl, H2O2, 39 degrees C and
      carbon starvation. Measurements of enzyme activity and intracellular sorbitol in
      wild-type cells also indicate that yeast aldose reductase is stress-regulated.
      Overexpression of GRE3 increases methylglyoxal tolerance in Saccharomyces
      cerevisiae. Furthermore, high expression of GRE3 complements the deficiency of
      the glyoxalase system of a glo1delta mutant strain. Consistent with this, in
      vitro and in vivo assays of yeast aldose reductase activity indicate that
      methylglyoxal is an endogenous substrate of aldose reductase. Furthermore,
      addition of NaCl or H2O2 to exponential-phase cells triggers an initial transient
      increase in the intracellular level of methylglyoxal, which is dependent on the
      Gre3p and Glo1p function. These observations indicate that the metabolism of
      methylglyoxal is stimulated under stress conditions; and they support a
      methylglyoxal degradative pathway, in which this compound is metabolised by the
      action of aldose reductase.

PMID- 11525400
TI  - Genome-wide expression analysis of a Saccharomyces cerevisiae strain deleted for
      the Tup1p-interacting protein Cdc73p.
AB  - Tuplp is a general corepressor in Saccharomyces cerevisiae. We performed a split
      ubiquitin screen with Tup1p as bait, in order to understand how Tuplp mediates
      repression. Cdc73p was the only component of a holoenzyme of transcription
      isolated as a Tuplp-interacting protein in this screen. Expression analysis of a
      strain deleted for CDC73 on a genome-wide scale revealed that Cdc73p is involved
      in the positive and negative regulation of transcription. Our results show that a
      subset of genes is regulated by both Cdc73p and Tup1p. Furthermore, our results
      indicate that Cdc73p plays a role in the repression of telomere-proximal genes,
      which are not repressed by Tup1p.

PMID- 11525401
TI  - Strains isogenic to S288C used in the yeast genome sequencing programme carry a
      functional KSS1 gene.
AB  - In Saccharomyces cerevisiae, the KSS1 gene encodes the MAP kinase of the
      invasive/filamentous growth pathway. In addition to its role in this signal
      transduction pathway, Kssl can replace the Fus3 MAP kinase in the pheromone
      response pathway, in the absence of FUS3. Previous work indicated that
      derivatives of the S288C strain carry a mutant kss1 allele. Here, we report
      evidence that S288C derivatives used in the Yeast Genome Sequencing Programme
      carry a functional KSS1 gene and can thus be used to study the regulation of gene
      expression by KSS1.

PMID- 11525402
TI  - Second-site, intragenic alterations in the gene encoding subunit II of cytochrome
      c oxidase from yeast can suppress two different missense mutations.
AB  - Cytochrome c oxidase, a multi-subunit enzyme complex, accepts electrons from
      cytochrome c and transfers them to molecular oxygen to form water. Subunit II
      (Cox2p) of the enzyme complex provides the initial entry site for the electrons
      from cytochrome c. We report here the characterization of a yeast strain bearing
      a mutation in the gene encoding Cox2p which abolishes the activity of the enzyme
      complex. The alteration, at residue 163 in the yeast polypeptide, substitutes
      isoleucine for threonine and leads to loss of Cox2p and loss of the ability to
      carry out cellular respiration. We have also characterized 55 independent
      revertants of the mutant which have recovered the ability to respire. Of these
      revertants, 37 recover the ability to respire due to a compensatory alteration at
      residue 163, which produces either a wild-type threonine codon or one for valine
      or serine. The other 18 revertants recover function due to secondary changes at
      four different codons within the gene encoding Cox2p. Some of these second-site,
      intragenic revertants occur at sites significantly distant from the position of
      the original mutation. In addition, alterations at two of these sites have
      previously been shown to suppress a completely different missense mutation in the
      gene.

PMID- 11525403
TI  - Isolation and characterization of the RAD59 homologue of Kluyveromyces lactis.
AB  - Homologous recombination in the yeast Saccharomyces cerevisiae is under the
      control of the RAD52 epistasis group. Genes belonging to this group show strong
      conservation during evolution and homologues of most members have been identified
      in other eukaryotic organisms such as Schizosaccharomyces pombe, Drosophila and
      mammals. A homologue of the ScRAD59 gene, which shows structural and functional
      overlap with ScRAD52, has not been identified in other organisms until now.
      Previous assessment of the ScRAD59 function revealed that the product of this
      gene is required for certain types of ScRAD51-independent recombination and
      single-strand annealing. Also, in the distantly related fission yeast, Sch.
      pombe, a second RAD52 homologue has been identified (rad/22B+), but this gene
      more closely resembles ScRAD52 than ScRAD59 at the amino-acid level. In this
      study, the isolation of a homologue of ScRAD59 in Kluyveromyces lactis, KlRAD59,
      is described. A Klrad159 null allele results in moderate sensitivity to X-rays,
      indicating that the KlRAD59 gene is involved in the repair of X-ray-induced DNA
      damage. The amino acids in the putative K1Rad59 protein share 53% identity and
      11% similarity with ScRad59. The KlRAD59 gene fully complements both the X-ray
      sensitive phenotype and defects in recombination of the Scrad59 mutant strain.
      Our results underscore the evolutionary conservation of the RAD52 group of genes
      and provide evidence that the presence of additional RAD52 homologues is not
      limited to Sac. cerevisiae and Sch. pombe and might be a general phenomenon.

PMID- 11525404
TI  - Carbon source-dependent transcriptional regulation of the QCR8 gene in
      Kluyveromyces lactis. Identification fo cis-acting regions and trans-acting
      factors in the KlQCR8 upstream region.
AB  - The QCR8 gene of the yeast K1uyveromyces lactis is transcriptionally regulated by
      the carbon source in the growth medium. Deletion analysis of the KlQCR8 promoter
      shows that an element located between -144 bp and -113 bp specifically controls
      induction of QCR8 gene expression on non-fermentable carbon sources. Specific and
      differential protein-binding to the activating sequence was observed with
      extracts from glucose- and ethanol/glycerol-grown cells. Induction of the
      reporter gene and protein-binding was dependent on the presence of a functional
      KlCAT8 gene, suggesting that, in K. lactis, K1Cat8p acts in the transcriptional
      regulation of respiratory function. The activating element contains no other
      known regulatory sites but two elements required for RNA holoenzyme functioning,
      raising the intriguing possibility of carbon source-dependent regulation by a
      subunit of the RNA polymerase holoenzyme in K. lactis.

PMID- 11525405
TI  - The grp78 promoter of Neurospora crassa: constitutive, stress and differentiation
      dependent protein-binding patterns.
AB  - In order to characterize the transcriptional regulation of the grp78 (glucose
      regulated protein 78 kDa) gene of Neurospora crassa, a 1.65-kb genomic fragment
      upstream of the protein-coding region was sequenced and analysed. A single
      transcription start point was mapped 160 nt upstream of the first codon. Several
      distinct protein-DNA binding sites were identified in the promoter region by non
      radioactive scanning electrophoretic mobility shift analysis during growth,
      stress treatment and differentiation of conidia. A protein DNA binding complex
      induced by tunicamycin was linked to a promoter motif similar to the unfolded
      protein response element consensus of yeast. Another binding complex in
      differentiating aerial hyphae was found, which differs from the known cis
      elements involved in conidiation-dependent gene expression.

PMID- 11525406
TI  - Induction of jlbA mRNA synthesis for a putative bZIP protein of Aspergillus
      nidulans by amino acid starvation.
AB  - The jlbA (jun-like hZIP) gene of Aspergillus nidulans was isolated. The deduced
      amino acid motif of the C-terminal region of jlhA encodes a putative DNA-binding
      site composed of a basic amino acid domain and an adjacent leucine zipper motif.
      This region shares highest similarities to the C-terminal DNA-binding domain and
      the basic zipper (bZIP)-motifs of transcription factors like CPCA from A. niger,
      Gcn4p from Saccharomyces cerevisiae, human JUNB and c-JUN. The putative jlbA
      protein contains a PEST-rich region (an instability region rich in the amino
      acids proline, glutamic acid, serine and threonine) described to be implicated in
      protein stability. The jlbA mRNA formation is elevated up to 40-fold upon amino
      acid starvation induced by the addition of the false feedback inhibitor 3-amino
      1,2,4-triazole. This induction is partially dependent and partially independent
      on the presence of the transcription factor CPCA. Therefore jlbA is a novel gene
      of A. nidulans which is transcriptionally activated by amino acid starvation
      conditions.

PMID- 11525407
TI  - Cloning and expression analysis of a new hydrophobin cDNA from the
      ectomycorrhizal basidiomycete Pisolithus.
AB  - Hydrophobins are fungal cell wall proteins which play a crucial role in cell
      adhesion and aggregative processes. We have identified a new hydrophobin cDNA
      (hydPt-3) in the symbiotic mycelium of Pisolithus tinctorius (putative P. albus)
      during the formation of ectomycorrhizae around eucalypt roots. This sequence is
      highly divergent from two other previously identified Pisolithus symbiosis
      regulated hydrophobins, hydPt-1 and hydPt-2. Also, expression analyses
      demonstrated that hydPt-3 is up-regulated during the formation of
      ectomycorrhizae. In contrast to phytopathogenic fungi, changes in glucose or
      ammonium concentrations in the growth medium did not influence the accumulation
      of any Pisolithus hydrophobin mRNAs. This suggests that other factors act as
      regulators of hydrophobin gene expression in ectomycorrhizae.

PMID- 11525408
TI  - The Aalpha6 locus: its relation to mating-type regulation of sexual development
      in Schizophyllum commune.
AB  - We have isolated and examined the Aalpha6 mating-type locus of Schizophyllum
      commune as a first step toward resolving a functional difference between this
      locus and the Aalpha loci previously studied. Our analyses show Aalpha6 to be
      remarkably similar to the Aalpha loci of known structure. The locus is composed
      of two, divergently transcribed genes similar in size to known Z and Y genes of
      the Aalpha loci. We have termed the two genes, Z6 and Y6, on the basis of their
      demonstrated mating activities and encoded protein motifs. The Z6 gene encodes a
      homeodomain-related sequence, two acidic regions and a predicted coiled-coil
      motif. The Y6 gene encodes a homeodomain, predicted coiled-coil motif, two
      regions with homology to the Abeta locus gene V6, a basic region encoding a
      putative nuclear localization sequence and a serine-rich region. The Z6 and Y6
      proteins share these features with the other known Z and Y proteins,
      respectively. One of the two amino acid sequences with homology to the AbetaV6
      protein has not previously been reported.

PMID- 11525409
TI  - Patterns of evolution in Discula fungi and the origin of dogwood anthracnose in
      North America, studied using arbitrarily amplified and ribosomal DNA.
AB  - The anthracnose epidemic caused by exotic filamentous fungi of the genus Discula
      threatens the future of the prized flowering (Cornus florida L.) and Pacific (C.
      nuttalli Aud.) dogwoods in North America. A cross-section of fungi that cause
      anthracnose in broadleaf temperate trees was characterized using DNA
      amplification fingerprinting, sequence and secondary structure analysis of the
      internal transcribed spacers (ITS) of nuclear ribosomal DNA (rDNA), and
      compatibility of hyphal anastomosis. ITS-inferred phylogenies rejected the null
      hypothesis of only one fungal lineage, by defining four monophyletic and well
      differentiated groups, corresponding to Discula sp., D. quercina, D. umbrinella
      and D. destructiva, with the last two species sharing a common and recent
      ancestor. In turn, they showed that the dogwood pathogen, D. destructiva, did not
      evolve directly from an indigenous population related to Discula sp. In this
      study, rDNA spacers that are generally considered important for protein synthesis
      but are selectively neutral, appeared functionally constrained and subject to
      selective sequence diversification. Results confirmed the high variability of D.
      umbrinella and the remarkable homogeneity and exotic nature of D. destructiva at
      the genetic level, clarified the taxonomy and phylogeny of Discula, and provided
      clues as to the origin and diversification of dogwood anthracnose-causing fungi.

PMID- 11525410
TI  - Transcript mapping and processing of mitochondrial RNA in Dictyostelium
      discoideum.
AB  - The circular mitochondrial genome of Dictyostelium discoideum has a size of
      55,564 base pairs. We present here a complete and detailed transcription map of
      the mitochondrial DNA. Eight major, polycistronic transcripts encoding
      polypeptides, ribosomal RNAs and interspersed transfer RNAs were identified in
      Northern hybridization studies. Most of these polycistronic transcripts are
      subsequently processed into smaller mono-, di- or tricistronic RNAs. In some
      cases, the maturation involves endonucleolytic cleavage of the transcripts using
      transfer RNAs as excision signals. Primer extension experiments mapped the 5'
      ends of the transcripts, which may represent transcription initiation sites. Two
      of the polycistronic transcripts were found to be overlapping. Based on sequence
      alignments of the potential transcription start sites, a short oligonucleotide
      consensus initiation sequence has been identified which does not reveal any
      significant sequence homologies to known promoter regions from other organisms.

PMID- 11525411
TI  - Highly efficient expression of rabbit neutrophil peptide-1 gene in Chlorella
      ellipsoidea cells.
AB  - A highly efficient system was developed for the expression of foreign genes in
      Chlorella ellipsoidea cells. The effect of five promoters on the expression
      efficiency of beta-glucuronidase (GUS) gene was evaluated by transient expression
      of the UidA gene. Among these promoters, Ubiquitin-omega was found to be the most
      efficient and was selected to drive the expression of foreign genes in Chlorella
      cells. A gene encoding the mature rabbit neutrophil peptide-1 (NP-1) was
      introduced into the cells. Integration of the gene for NP-1 into the Chlorella
      genome was confirmed by PCR and Southern blot analysis. In, vitro anti-microbial
      testes demonstrated the expression of biologically active NP-1 by the transgenic
      Chlorella cells.

PMID- 11525412
TI  - Mitochondrial atp6 transcript editing during microgametogenesis in male-sterile
      sorghum.
AB  - A marked reduction of mitochondrial atp6 transcript-editing capability in sorghum
      anthers and pollen has been invoked as a factor in the loss of viability of male
      gametophytes in lines carrying the IS1112C male-sterile cytoplasm. We initiated a
      systematic examination of transcript editing of sorghum atp6 during
      microgametogenesis, from microspores through pollen, in two sets of male-fertile
      and near-isogenic, male-sterile lines. Transcript editing in cDNA populations
      from fertile lines indicated an average of about 90% editing among 15 sites
      examined. Parallel samples from sterile lines demonstrated a detectable reduction
      in editing efficiency, most evident in late pollen samples. However, editing
      efficiency in these cells averaged 80%, substantially higher than the 20%
      previously observed. Thus male-sterile lines retain substantial atp6-editing
      efficiency in an environment where the sterility and fertility restoration traits
      are stably expressed. Drastically reduced editing of atp6 transcripts in anthers
      and pollen of male-sterile sorghum is not demonstrable in a field environment;
      and thus it is not a factor in the loss of microgametophyte viability in this
      system.

PMID- 11525413
TI  - A new MFS-transporter gene next to the gibberellin biosynthesis gene cluster of
      Gibberella fujikuroi is not involved in gibberellin secretion.
AB  - The genes of the gibberellin (GA) biosynthesis pathway in Gibberella fujikuroi
      are organized in a gene cluster consisting of at least seven genes. Here we
      report the cloning and characterization of smt, a gene encoding a membrane
      transporter of the major facilitator super-family 1, which is located next to the
      GA gene cluster. Since pathway-specific transporters occur frequently in
      prokaryotic and fungal antibiotic and toxin clusters, smt was thought to be
      involved in GA secretion. The gene is expressed in mycelium grown under GA
      production conditions, but not when the GA biosynthesis is repressed by high
      amounts of ammonium. To investigate the function of SMT, gene replacement
      experiments were performed. The smt-mutants did not show any reduction in the GA
      yield; and gibberellic acid or its precursors did not influence the gene
      expression. However, sugar alcohols, such as myo-inositol, sorbitol and mannitol,
      induced the expression of smt. The results demonstrate that the smt gene does not
      play an essential role in biosynthesis and secretion of GAs in G. fujikuroi,
      despite the location adjacent to the GA gene cluster.

PMID- 11525414
TI  - RNA editing in higher plant plastids: oligoribonucleotide SSCP analysis allows
      the proof of base conversion directly at the RNA level.
AB  - Plastid RNA editing of a number of transcripts at specific sites changes
      genomically encoded cytidines to nucleosides, which act like uridines in RT-PCR
      analyses. To study plastid-editing directly at the RNA level, we established a
      single-strand conformational polymorphism assay for the discrimination of small
      RNA molecules. The electrophoretic mobility of a oligoribonucleotide resulting
      from a RNase T1-digested and edited plastid mRNA was shown to be identical with a
      control RNA molecule containing a uridine at the editing site, whereas the
      unedited RNA behaved like a RNA molecule containing a cytidine at the respective
      position.

PMID- 11525415
TI  - Efficient Agrobacterium tumefaciens-mediated gene disruption in the phytopathogen
      Mycosphaerella graminicola.
AB  - Agrobacterium tumefaciens-mediated transformation has been successfully applied
      to the wheat pathogen Mycosphaerella graminicola. Both protoplasts and intact
      cells have been transformed to hygromycin B resistance. Furthermore, A.
      tumefaciens-mediated transformation using homologous DNA originating from the M.
      graminicola ABC transporter gene MgAtr2 resulted in the efficient generation of
      disruption mutants. In 44% of the transformants, disruption of MgAtr2 was
      achieved and transformants resulted from the integration of a single copy of the
      transforming DNA. These results indicate that A. tumefaciens-mediated
      transformation is a useful tool to generate targeted gene disruption in the
      phytopathogen M. graminicola, where gene targeting by conventional methods is
      hardly possible.

PMID- 11525416
TI  - Characterization of a minisatellite repeat locus in the chloroplast genome of
      Orchis palustris (Orchidaceae).
AB  - We describe the occurrence of a tandem repeat in the chloroplast genome of the
      marsh orchid, Orchis palustris. The repeat unit is an AT-rich, 16-bp sequence
      located in the chloroplast tRNALEU intron. Southern blot analysis confirmed that
      the O. palustris tRNALEU intron including the minisatellite locus has not been
      transferred to the nucleus, but is indeed located on the chloroplast genome. The
      16-bp repeat unit was found to be present in all O. palustris accessions studied,
      as well as in the closely related O. laxiflora. Variation in repeat numbers among
      individuals was found in O. palustris from central and northern Italy; and this
      was consistently associated with a 13-bp sequence motif preceding the repeat.
      This motif was absent from O. palustris from southern Italy, Greece, and from O.
      laxiflora. In these accessions, no variation in repeat numbers was found. Our
      results suggest that the O. palustris chloroplast minisatellite locus evolved
      relatively recently, presumably in central Italy, and may represent a valuable
      marker for population genetic studies.

PMID- 11525417
TI  - Catechol-O-methyltransferase gene polymorphism in schizophrenia: evidence for
      association between symptomatology and prognosis.
AB  - Catechol-O-methyltransferase (COMT) gene has long been implicated to play a role
      in the pathogenesis of schizophrenia. The aim of this study is to assess the
      relationship of schizophrenia and its subgroups with COMT gene polymorphism. We
      have attempted to evaluate a possible correlation between the severity and
      prognosis of the illness (the psychopathology of symptoms) and COMT gene
      polymorphisms. The study comprised 129 unrelated subjects who strictly met DSM-IV
      criteria for schizophrenia, and 65 healthy unrelated controls. All subjects were
      of Turkish origin. A clinical evaluation of all patients was accomplished by
      applying the Brief Psychiatric Rating Scale (BPRS) test. The analysis of COMT
      polymorphism was performed using the polymerase chain reaction technique.
      Regarding COMT gene polymorphisms, no statistically significant difference was
      found between schizophrenic patients and control subjects. However, within the
      schizophrenic group, the average of BPRS points of patients with the L/L genotype
      was significantly higher than those of the L/H and H/H genotypes (F = 6.25,
      degrees of freedom = 2, P = 0.003). Although no statistically significant
      difference was found between the duration of illness and COMT variations, a
      higher frequency of hospitalization was found in patients with the L/L genotype
      compared with other groups (t = 3.048, P = 0.003). In conclusion, the findings
      indicate that COMT gene polymorphisms were not statistically significant between
      patient and control groups. However, the patients with the L/L genotype may have
      much more severe clinical signs in Turkish schizophrenics. COMT variations,
      however, do not help to evaluate the susceptibility of the patients, but can help
      in the estimation of severity of clinical manifestations. Further studies are
      required to better understand the association of symptomatology of schizophrenia
      and other psychiatric disorders with COMT gene polymorphism.

PMID- 11525418
TI  - Chromosomal abnormalities in a clinic sample of individuals with autistic
      disorder.
AB  - We examined data from the largest reported sample of autistic individuals who
      have been karyotyped with the aim of providing additional information in the
      search for autism disease genes. Individuals seen in the University of Iowa's
      Child and Adolescent Psychiatry Clinic since 1980 who had been diagnosed with
      autism were cross-referenced with the University of Iowa's Cytogenetics
      Laboratory database. We determined the number of individuals referred for
      cytogenetic testing and, of these, the number found to have gross cytological
      abnormalities. Medical records were reviewed for all cases with such
      abnormalities. Between 1980 and 1998, 898 subjects seen in the clinic were
      diagnosed with autism. Of these, 278 (30.1%) were referred for cytological
      studies; 25 (9.0%) of these were found to have chromosomal abnormalities. The
      most common chromosomal abnormalities were Fragile X, other sex chromosome
      anomalies, and chromosome 15 abnormalities. These data support the contribution
      of chromosomal abnormalities to a small but significant number of cases of
      autism, and highlight the involvement of chromosome 15 and the sex chromosomes.

PMID- 11525419
TI  - Parasomnias: co-occurrence and genetics.
AB  - In clinical practice, parasomnias are often found to run in families and to co
      occur. Several studies have indicated a role of genetic factors in them. In 1990,
      a questionnaire (response rate, 77%) sent to the Finnish Twin Cohort, a
      representative population sample aged 33-60 years, surveyed the frequency of five
      parasomnias (sleepwalking, sleeptalking, enuresis, bruxism, and nightmares) in
      childhood and as adults. In assessing the phenotypic covariation and shared
      genetic effects between the parasomnias, we used polychoric correlations and
      structural equation modelling. In childhood (n = 5856 individuals), co-occurrence
      is highest in sleeptalking with sleepwalking (R = 0.73), nightmares (R = 0.50),
      and bruxism (R = 0.43). As adults (n = 8567), the results are similar (R = 0.56,
      0.43, and 0.39, respectively). The analyses of shared genetic effects included
      815 monozygotic and 1442 dizygotic twin pairs with complete responses on four
      parasomnias as adults. The strongest genetic covariation was found in
      sleeptalking with sleepwalking, sleeptalking with bruxism, and in sleeptalking
      with nightmares. The estimated proportions of shared genetic effects were 50, 30,
      and 26%, respectively. The present results indicate that parasomnias share some
      common genetic background.

PMID- 11525420
TI  - Identification of polymorphisms within Disrupted in Schizophrenia 1 and Disrupted
      in Schizophrenia 2, and an investigation of their association with schizophrenia
      and bipolar affective disorder.
AB  - We have undertaken a search for polymorphic sequence variation within Disrupted
      in Schizophrenia 1 and Disrupted in Schizophrenia 2 (DISC1 and DISC2), which are
      both novel genes that span a translocation breakpoint strongly associated with
      schizophrenia and related psychoses in a large Scottish family. A scan of the
      coding sequence, intron/exon boundaries, and part of the 5' and 3' untranslated
      regions of DISC1, plus 2.7 kb at the 3' end of DISC2, has revealed a novel
      microsatellite and 15 novel single nucleotide polymorphisms (SNPs). We have
      tracked the inheritance of four of the SNPs through multiply affected families,
      and carried out case-control association studies using the microsatellite and
      four common SNPs on populations of patients with schizophrenia or bipolar
      affective disorder versus normal control subjects. Neither co-segregation with
      disease status nor significant association was detected; however, we could not
      detect linkage disequilibrium between all these markers in the control
      population, arguing that an even greater density of informative markers is
      required to test rigorously for association in this genomic region.

PMID- 11525421
TI  - Mutation screening of the metabotropic glutamate receptor mGluR4 (GRM4) gene in
      patients with schizophrenia.
AB  - Disturbances in glutamate function have been implicated in the pathophysiology of
      schizophrenia. We searched for mutations in the exons of the metabotropic
      glutamate receptor mGluR4 (GRM4) gene on human chromosome 6p21.3 and evaluated
      associations between these polymorphisms with schizophrenia in Japanese patients.
      Nine nuclear variants of 450G > T, 1455T > C, 2202A > G, 2389G > A (Val797 >
      Ile797), 2890A > G, 3601C > T, 3639C > T, IVS4-36G > A, and IVS5 + 29(CCGGG)1-2,
      were found. The Val797Ile variant, although found in both the patient and control
      groups, was rare and the only variant that causes a non-synonymous amino acid
      change. There was no statistically significant association between any mGluR4
      gene polymorphism and schizophrenia. Thus, this study did not provide evidence
      for the contribution of the mGluR4 gene to schizophrenia in the Japanese.

PMID- 11525422
TI  - Obsessive-compulsive disorder and a novel polymorphism adjacent to the oestrogen
      response element (ERE 6) upstream from the COMT gene.
AB  - Family and twin studies have consistently provided evidence for involvement of
      genetic mechanisms in obsessive-compulsive disorder (OCD). This has given rise to
      association studies involving several candidate genes in an endeavour to identify
      susceptibility factors. One of the more promising candidate genes appears to be
      the catecol-O-methyltransferase (COMT) gene. Recent association studies in North
      American and Afrikaner populations have reported a likely association between a
      functional polymorphism of COMT (linked with COMT enzyme activity levels) and
      OCD. COMT expression has been demonstrated to be regulated by oestrogen through
      the oestrogen-response elements (EREs) in the promoter region of the gene. In the
      light of this association, the authors tested for an association between a novel
      polymorphism (C --> T transition) adjacent to ERE 6 in the promoter area of COMT
      and OCD in 48 Afrikaners and 48 ethnically matched controls. The C --> T
      transition was not significantly associated with OCD (P = 0.93) or gender (P =
      0.67). These findings, although limited by a small sample size, suggest that the
      novel polymorphism adjacent to ERE 6 in the promoter area of COMT does not play a
      major role in the genetic predisposition to OCD.

PMID- 11525423
TI  - Serotonergic pathway genes and subtypes of alcoholism: association studies.
AB  - Disturbances of the serotonergic pathway have been implicated in many psychiatric
      disorders, including alcoholism, aggression, schizophrenia and depression. The
      personality dimension of harm avoidance is correlated positively with the
      activity of mesolimbic serotonergic neurons. The goal of this study was to
      determine the role of the genes in this pathway in the development of type II
      alcoholism. A sample of alcoholics and normal controls were screened with the
      variations in tryptophan hydroxylase (TPH), serotonin receptors (5-HT2A and 5
      HT2C), serotonin transporter (5-HTT), and monoamine oxidase A (MAO-A) genes. The
      results of association studies for type II alcoholics were the most significant
      with 5-HTT (P = 0.011) and MAO-A (P = 0.029) genes. However, after correction for
      multiple comparisons, none of the results reached the significance level. These
      data indicate that the genes in the serotonergic pathway may be involved in the
      development of type II alcoholism but the gene effects are very small.

PMID- 11525424
TI  - Estrogen receptor alpha gene polymorphism in schizophrenia: frequency, age at
      onset, symptomatology and prognosis.
AB  - Schizophrenic disorders are equally distributed for both sexes; however, later
      onset, milder psychopathology and better outcome are associated with the female
      gender. This sex difference is thought to be partly due to the estrogen system.
      Recent studies have determined that estrogen receptor alpha subtype (ER alpha)
      genetic polymorphisms may affect the expression of ER alpha, and are associated
      with Alzheimer's disease. For this study, we investigated the association of ER
      alpha polymorphisms for 125 schizophrenic patients and 142 control subjects. No
      significant differences for genotype distribution or allele frequency were
      revealed comparing controls and schizophrenic patients. The ER alpha genotypes
      were not associated with onset age, psychiatric symptoms or outcome for
      schizophrenic cases. With new research highlighting the prominent role of sex
      hormones in neurological and psychological dysfunction, further study is needed
      to explore the genetic effect of the sex hormone receptor gene on susceptibility
      mental disorders and associations with different phenotypes.

PMID- 11525425
TI  - No association between the 4g/5G polymorphism of the plasminogen activator
      inhibitor-1 gene promoter and autistic disorder.
AB  - Plasmin, a serine protease, is involved in many physiologically relevant
      processes, including haemostasis, cellular recruitment during immune response,
      tumour growth, and also neuronal migration and synaptic remodelling. Both tissue
      type and urokinase-type plasminogen activators can be efficiently inhibited by
      plasminogen activator inhibitor-1 (PAI-1), a protease inhibitor of the serpin
      family. The human PAI-1 gene is located on chromosome 7q, within or close to a
      region that has been linked to autism in several linkage studies. Autism seems to
      be characterized by altered neuronal cytoarchitecture, synaptogenesis and
      possibly also cellular immune responses. We began addressing the potential
      involvement of the PAI-1 gene in autistic disorder with this linkage/association
      study, assessing transmission patterns of the 4G/5G polymorphism in the PAI-1
      gene promoter that was previously shown to significantly affect PAI-1 plasma
      levels. No linkage/association was found in 167 trios with autistic probands,
      recruited in Italy and in the USA. We thus found no evidence that this
      polymorphism, or putative functionally relevant gene variants in linkage
      disequilibrium with it, confer vulnerability to autistic disorder.

PMID- 11525426
TI  - Urban structures as marine habitats: an experimental comparison of the
      composition and abundance of subtidal epibiota among pilings, pontoons and rocky
      reefs.
AB  - There remains little understanding of the relationship between the ecologies of
      urban habitats (pilings and pontoons) and natural habitats (rocky reef) for
      sessile plants and animals (epibiota) living on urbanised coasts. This study
      describes the structure of subtidal assemblages of epibiota among pilings,
      pontoons and adjacent rocky reef in Sydney Harbour, Australia. I tested the
      prediction that the experimental provision of substrata of the same age and
      composition in all three habitats would produce assemblages that: (1) differed
      among all three habitats; and (2) differed most on floating pontoons relative to
      the two fixed habitats (pilings and reef). As predicted, the results suggested
      that both pilings and pontoons, particularly the latter, create novel habitats
      for epibiotic assemblages independent of age and composition of substratum. It is
      not fully understood why these urban structures act as such different habitats
      from natural rocky reefs. The important point is that they are different and we
      are yet to understand the implications of this for the ecology of coastal areas
      subject to urbanisation.

PMID- 11525427
TI  - An efficient clean-up method for the GC-MS determination of methylsulfonyl
      PCBs/DDEs extracted from various marine mammal tissues.
AB  - Existing methods for analyzing methylsulfonyl-PCBs in animal tissues require
      multiple laborious clean-up steps prior to quantitation. In this paper, we report
      a new, efficient method for the isolation and determination of methylsulfonyl-PCB
      metabolites in the blubber, liver, kidney, lung, and milk from mammals of marine
      origin using: solvent extraction, GPC fractionation, and clean-up on an
      adsorption chromatography column prior to analysis by gas chromatography-mass
      spectrometry. The method is rapid and can be completed in about half the analysis
      time required by most other reported methods. The method exhibits excellent
      analyte recoveries (89-95%), and good reproducibilities with CV's ranging from 3
      12% depending on analyte concentration. Detection limits are approximately 1 ng/g
      lipid. The method is further validated by comparing its quantitative results to
      that of an independent reference analytical method for several different marine
      mammal blubber samples. Finally, the method is applied to profile the
      distribution of methylsulfones among the various tissue types studied for a
      single bottle-nose dolphin (Tursiops truncatus) sample. In addition, the extent
      of their transplacental transfer from mother to unborn fetus for several pilot
      whale (Globicephala melaena) mother-fetus pairs is examined.

PMID- 11525428
TI  - Hepatic metallothionein as a biomaker for metal contamination: age effects and
      seasonal variation in European flounders (Pleuronectes flesus) from the Severn
      Estuary and Bristol Channel.
AB  - Hepatic concentrations of metallothionein [MT] and three metals (Cu, Zn, Cd) were
      determined in 242 European flounders (Pleuronectes flesus) collected from power
      stations at Oldbury-upon-Severn and Hinkley Point, located in Severn Estuary and
      Bristol Channel, UK, respectively, between March 1996 and February 1998. A model
      involving three-factor analysis of variance (ANOVA) was used to examine variation
      in MT and metal concentrations with respect to season, year and site; with age
      class included as a covariate in the analysis. Hepatic concentrations of MT and
      Cd (and to some degree, Cu, but not Zn) increased significantly with age. The
      model explained 38, 25, 17 and 26% of the variation in MT, Cu, Zn and Cd,
      respectively, with significant effects due to season, and to a lesser extent, to
      year. Site was only a significant factor for Cd which was higher in fish from
      Hinkley. Correlation between the individual concentration of MT and each metal
      alone, or in combination, was poor, and explained only an additional 3.0% of the
      residual variation in MT, most of which was attributable to Cu (2.7%). Compared
      to other industrialised estuaries, Cd concentrations were high (>20 micro g-1 in
      some individuals). The study emphasises the importance of seasonal variation and
      other factors in biomonitoring programmes and highlights the limitations of using
      [MT] as a biomarker for metal contamination in flounders from the Severn Estuary.

PMID- 11525429
TI  - Survival, growth, metallothionein and glycogen levels of Nucella lapillus (L.)
      exposed to subchronic cadmium stress: the influence of nutritional state and prey
      type.
AB  - Dogwhelks Nucella lapillus feed mainly on mussels and barnacles, and may
      experience periods of starvation. We report effects of nutritional state and prey
      type on the survival, growth, cadmium (Cd) accumulation, metallothionein (MT)
      induction and glycogen stores in N. lapillus exposed to Cd in water. Adult
      dogwhelks, with similar shell length (30.0+/-1.5 mm), were either starved or fed
      to satiation with barnacles Semibalanus balanoides, mussels Mytilus edulis or Cd
      dosed M. edulis, and kept in filtered natural seawater (< 0.01 microg Cd 1(-1))
      or Cd-contaminated (400 microg Cd 1(-1)) seawater for 80 days. Mortality and
      individual growth rate were determined. Cd, MT and glycogen were measured in
      different tissues. Prolonged starvation and exposure to Cd significantly reduced
      the survivorship of N. lapillus, but feeding could help dogwhelks to combat Cd
      toxicity and minimise mortality. Extended starvation also caused tissue wastage,
      leading to higher concentrations of Cd and MT in tissues, whereas fed animals
      increased in weight and had lower Cd and MT concentrations because of the tissue
      dilution effect. Prey type significantly affected growth rate of dogwhelks and
      indirectly influenced Cd accumulation, MT induction and glycogen stores. Eating
      mussels promoted better growth and higher glycogen reserves than eating
      barnacles. Individual growth rate decreased with increasing Cd accumulation. Cd
      exposed survivors grew faster and consumed more than control animals, implying
      that these survivors may have better fitness and greater tolerance to Cd
      toxicity. The use of growth, condition index, MT and glycogen as biomarkers of
      environmental pollution are discussed. These results indicate a need to
      incorporate biological data including growth (or at least condition index) and
      prey type into biomonitoring programmes to allow sound interpretation.

PMID- 11525430
TI  - Caprella watch: a new approach for monitoring butyltin residues in the ocean.
AB  - A comparative study on the butyltin levels in various organisms showed that
      marked bioaccumulation occurs in certain lower trophic levels; i.e. from seawater
      to phytoplankton and into caprellid amphipods, Caprella spp. Caprella spp., which
      inhabit algal communities and aquaculture beds in the subtidal zone, are small
      crustaceans with reduced movement and a life-span of less than 3 months. These
      characteristics indicate that Caprella spp. may be well-suited for monitoring
      butyltin residue changes over small spatial and temporal scales. Two groups of
      organisms, mussels and neogastropods, have been mainly used for monitoring
      butyltin in shallow water ecosystems. These invertebrates mainly inhabit the
      intertidal zone where the butyltin levels vary widely depending on the immersion
      period and exposure to the sea surface microlayer. Monitoring using neogastropods
      may also over estimate exposures after restrictions on tributyltin, since
      neogastropods show an irreversible response to residue changes owing to their
      long life-spans. Thus, we propose usage of Caprella spp. to monitor temporal and
      spatial changes in baseline concentrations of butyltins.

PMID- 11525431
TI  - The natural history of periodontal disease in man. Risk factors for progression
      of attachment loss in individuals receiving no oral health care.
AB  - BACKGROUND: Few investigations have reported on risk factors for periodontal
      attachment loss over time in subjects with no home or professional dental care.
      The purpose of this report was to identify potential risk factors for progression
      of periodontal attachment loss among male Sri Lankan tea laborers who
      participated in a 20-year investigation of the natural history of periodontal
      disease. METHODS: Data for this report were obtained from the 154 subjects who
      participated in the 1970 baseline and the final 1990 examinations and included
      data from their interim examinations performed in 1971, 1973, 1977, 1982, and
      1985. Oral health assessments included: 1) attachment levels in millimeters on
      mesial and mesio-buccal surfaces of all but third molar teeth; 2) plaque index
      (PI); 3) gingival index (GI); 4) calculus index (CI); 5) caries index (DMFS); and
      6) presence or absence of teeth. Other variables included age, history of
      smoking, and/or use of betel nut. Statistical analyses used multivariate repeated
      measures analysis of variance (ANOVA). RESULTS: The final adjusted model
      indicated that attachment loss increased significantly with age (X2 = 74.0; df =
      1), GI (X2 = 45.5; df = 1), CI (X2 = 52.7; df = 1) and follow-up time (X2 =
      219.8; df = 6, P<0.0001 for all variables). CONCLUSIONS: Age, GI, CI, and time
      were significantly associated with mean attachment loss over 20 years. Neither
      PI, history of smoking, or history of betel nut use were significantly associated
      with attachment loss over time.

PMID- 11525432
TI  - Flow cytometry analysis of guided tissue regeneration-associated human
      periodontal cells.
AB  - BACKGROUND: Expanded polytetrafluoroethylene (ePTFE) barrier membranes have been
      widely used for guided tissue regeneration (GTR) of the human periodontal
      ligament (PL). However, the precise cellular and molecular events involved in the
      re-growth of the new tissue are still unclear. METHODS: Retrieved membranes and
      the newly-regenerated soft tissue (RT) underlying the membranes were used to
      examine the cells associated with GTR compared with normal human PL and gingival
      cells. Flow cytometry (FCM) was used, for the first time, to analyze the spindle
      shaped fibroblast-like cells which were adherent to these membranes and the cells
      which grew out of the RT. RESULTS: The results showed that the membrane
      associated (M) cells had the lowest rate of proliferation and appeared to be
      larger and more granular than the other types of cell. Moreover, both the M- and
      RT-derived cells were found to express higher levels of the extracellular matrix
      (ECM) proteins collagen type 1, fibronectin, tenascin, and decorin. In addition,
      evidence based on FCM profiles identified distinct sub-populations of GTR cells
      in which fibronectin expression was markedly up-regulated compared with normal PL
      cells and which also differed in size and granularity. CONCLUSIONS: The results
      of this study show that cells associated with GTR barrier membranes and with the
      underlying tissue appear to have distinct phenotypic and functional activities
      consistent with the production of new periodontal connective tissue and
      periodontal regeneration.

PMID- 11525433
TI  - Levels of leukotriene B4 in gingival crevicular fluid and gingival tissue in
      specific periodontal diseases.
AB  - BACKGROUND: Leukotriene B4 (LTB4), a product of the lipoxygenase pathway of
      arachidonic acid metabolism, exhibits numerous activities that can account for
      most of the features of host responses seen in periodontal diseases. The aim of
      the present study was to examine the role of LTB4 in the pathogenesis of specific
      periodontal diseases. METHODS: LTB4 levels were investigated in gingival
      crevicular fluid (GCF) and gingival tissue (GT) samples of 10 patients with
      chronic periodontitis (CP), 12 patients with generalized aggressive periodontitis
      (GAgP), 6 patients with localized aggressive periodontitis (LAgP), 6 patients
      with gingivitis (G), and 6 periodontally healthy subjects (H). Periodontal status
      was evaluated by measuring probing depth, gingival index, papillary bleeding
      index, and plaque index. LTB4 was extracted from the samples by solid-phase
      method using C18 cartridge and was purified by high performance liquid
      chromatographic method and then analyzed by radioimmunoassay. RESULTS: All
      patient groups had significantly higher levels of GCF and GT LTB4 compared to the
      control group (P<0.005). The CP patients had the highest LTB4 levels compared to
      those in other patient groups (P<0.005). GAgP, LAgP, and G groups had similar
      amounts of GCF and GT LTB4 (P>0.005). When the data were expressed as
      concentration, the CP group was found to have higher concentration of LTB4,
      compared to that of control group (P<0.005). GAgP, LAgP, and G groups had similar
      LTB4 concentration compared to that of control group (P>0.005). No significant
      difference was found between GAgP, LAgP, and G groups (P>0.005). The CP group had
      higher LTB4 concentration compared to both GAgP and LAgP groups (P<0.005).
      Although the CP group had a higher GCF LTB4 concentration compared to G group,
      this difference did not reach significance (P>0.005). No significant correlation
      was found between GCF and GT LTB4 levels and clinical parameters. CONCLUSIONS:
      The results of the present study indicate that LTB4 is likely to be an important
      mediator in regulating inflammatory responses in the human periodontal tissues.
      This lipid mediator may play an important role in the pathophysiology of
      periodontal disease.

PMID- 11525434
TI  - Levels of platelet-activating factor in gingival crevicular fluid and gingival
      tissue in specific periodontal diseases.
AB  - BACKGROUND: Platelet-activating factor (PAF), a potent phospholipid mediator of
      inflammatory and immune reactions, is involved in a variety of biological
      responses seen in periodontal diseases. The aim of the present study was to
      examine the role of PAF in the pathogenesis of specific periodontal diseases.
      METHODS: PAF levels were investigated in gingival crevicular fluid (GCF) and
      gingival tissue (GT) samples of 12 patients with generalized aggressive
      periodontitis (GAgP), 6 patients with localized aggressive periodontitis (LAgP),
      10 patients with chronic periodontitis (CP), 6 with gingivitis (G), and 6
      periodontally healthy subjects (H). Periodontal status was evaluated by measuring
      probing depth, gingival index, papillary bleeding index, and plaque index. PAF
      was extracted from GCF samples passing through amberlit resin columns, purified
      by high performance liquid chromatographic method, and then analyzed by
      radioimmunoassay. RESULTS: GAgP, LAgP, and CP groups had significantly higher GCF
      PAF levels compared to the H group (P<0.005). Although statistically not
      significant, GCF PAF levels were also higher in the G group than those of the H
      group (P = 0.0784). GAgP, LAgP, and CP groups had similar GCF PAF levels
      (P>0.005). These groups had higher levels of GCF PAF than those of the G group,
      but the difference was significant only for the GAgP group (P<0.005). When the
      data were expressed as concentration, GAgP, LAgP, and CP groups were found to
      have higher concentrations of GCF PAF compared to the H group (P<0.005). GCF PAF
      concentration was similar in patient groups (P>0.005). All patient groups had
      significantly higher GT PAF levels compared to the H group (P<0.005). GAgP, LAgP,
      and CP groups had similar amounts of GCF and GT PAF (P>0.005). GAgP, LAgP, and CP
      groups had higher GT PAF levels than those of the G group, but the differences
      were only significant for LAgP and CP groups (P<0.005). No significant
      correlation was found between GCF and GT PAF levels and clinical parameters.
      CONCLUSIONS: The results of the present study indicate that PAF is likely to be
      an important mediator in regulating inflammatory responses in the human
      periodontal tissues. To our knowledge, this is the first report investigating PAF
      levels in GCF and GT in specific periodontal diseases. We believe that this
      potent phospholipid mediator may need to be considered in the pathogenesis of
      periodontal diseases.

PMID- 11525435
TI  - Regulation of cytokine production in human gingival fibroblasts following
      treatment with nicotine and lipopolysaccharide.
AB  - BACKGROUND: Patients who smoke are at increased risk for chronic periodontitis
      (CP). Most studies suggest that the microbial flora in these patients is similar
      to that found in non-smoking CP patients. Thus, the increased risk for
      development of CP is not dependent on an altered microbial profile, but rather to
      some change in the host response to these periopathogens. There is evidence that
      human gingival fibroblasts (HGF) derived from diseased sites produce greater
      amounts of interleukin (IL)-6 and IL-8 in vitro than cells derived from healthy
      sites. This suggests that HGF subpopulations may be selected based upon the
      inflammatory milieu in which they reside. The hypothesis to be tested was that
      the combination of nicotine and lipopolysaccharide (LPS) could regulate HGF
      inflammatory mediator production. METHODS: HGF cell cultures were established
      from explants derived from 10 patients with CP. HGF cell cultures were stimulated
      with 1 mM, 1 microM, or 1 nM nicotine +/- Escherichia coli or Porphyromonas
      gingivalis LPS. At 12, 24, or 48-hour time points, the cells were counted and the
      supernatant was collected for subsequent IL-6 and IL-8 determination in an enzyme
      linked immunosorbent assay. RESULTS: At the 24-hour time point, 1 nM nicotine
      stimulated IL-6 production compared to control (P=0.02). E. coli LPS alone caused
      a 3- to 4-fold increase in IL-6 and IL-8 production, whereas P gingivalis LPS did
      not augment IL-6 or IL-8. A synergistic effect upregulating IL-6 was observed
      with combined treatment of 1 mM nicotine and E. coli LPS or P gingivalis LPS at
      the 24-hour time point (P<0.0005 and P=0.002, respectively). Similar effects were
      seen when IL-8 production was evaluated following HGF stimulation with high doses
      of nicotine and E. coli LPS or P gingivalis LPS. CONCLUSIONS: These results
      demonstrate that nicotine by itself can stimulate HGF IL-6 and IL-8 production.
      Moreover, the combination of high doses of nicotine and either E. coli or P
      gingivalis LPS can synergistically upregulate cytokine production. These findings
      support the hypothesis that a proinflammatory fibroblast phenotype may be
      elicited in an environment enriched with bacterial LPS and nicotine.

PMID- 11525436
TI  - Effect of non-surgical periodontal therapy on C-telopeptide pyridinoline cross
      links (ICTP) and interleukin-1 levels.
AB  - BACKGROUND: Biochemical markers harvested from gingival crevicular fluid (GCF)
      may be useful to identify and predict periodontal disease progression and to
      monitor the response to treatment. C-telopeptide pyridinoline cross-links (ICTP),
      a host-derived breakdown product specific for bone, and interleukin-1beta (IL-1),
      a potent bone-resorptive cytokine, have been associated with periodontal tissue
      destruction. The aim of this study was to examine the effect of non-surgical
      periodontal therapy on GCF levels of ICTP and IL-1. METHODS: Twenty-five chronic
      periodontitis subjects were monitored at 8 sites per subject at baseline prior to
      scaling and root planing and 1, 3, and 6 months after therapy. Four shallow
      (probing depths < 4 mm) and 4 deep (probing depths > or = 5 mm) sites were
      monitored for both marker levels and clinical parameters. GCF was collected for
      30 seconds on paper strips, and levels of ICTP and IL-1 were determined using
      radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA) techniques,
      respectively. Clinical measurements included probing depth (PD), clinical
      attachment level (CAL), and bleeding on probing (BOP). RESULTS: Deep sites
      exhibited significantly (P<0.001) higher ICTP and IL-1 levels compared to shallow
      sites at all time intervals. ICTP demonstrated a stronger association to clinical
      parameters than IL-1 including a modest correlation (r = 0.40, P<0.001) between
      ICTP and attachment loss. Significant improvements in PD, CAL, and BOP were
      observed at 1, 3, and 6 months in all sites (P<0.01). However, non-surgical
      mechanical therapy did not significantly reduce ICTP and IL-1 levels over the 6
      month period. Further examination of subjects based on smoking status revealed
      that ICTP levels were significantly reduced at 3 and 6 months and IL-1 levels
      reduced at 3 months among non-smokers only. CONCLUSIONS: A single episode of non
      surgical mechanical therapy did not significantly reduce biochemical markers
      associated with bone resorption in patients exhibiting chronic periodontitis.
      Future longitudinal studies are warranted to specifically evaluate the
      relationship between C-telopeptide pyridinoline cross-links and periodontal
      disease progression.

PMID- 11525437
TI  - Nitric oxide synthase activity in neutrophils from patients with localized
      aggressive periodontitis.
AB  - BACKGROUND: Localized aggressive periodontitis (LAgP) is associated with
      neutrophil dysfunction including defective chemotaxis and reduced calcium influx
      factor activity. Nitric oxide (NO) and its enzyme, nitric oxide synthase (NOS),
      have been suggested to be involved in chemotaxis. Some reports, however, were
      unable to detect either NO or NOS in human neutrophils. In this study, we focused
      on NOS activity in LAgP neutrophils and examined the involvement of NOS in
      chemotaxis of normal neutrophils and NOS activity in neutrophils from normal
      subjects and patients with LAgP. METHODS: Neutrophils from 10 normal subjects and
      10 LAgP patients were isolated from peripheral venous blood. Membrane associated
      NOS (MA-NOS) and soluble NOS (S-NOS) were extracted from cells with or without
      FMLP stimulation. NOS activity was measured using the radiolabeled L-arginine to
      L-citrulline conversion assay. RESULTS: N(omega)-nitro-L-arginine methyl ester (L
      NAME), an inhibitor of NOS, significantly inhibited FMLP-induced chemotaxis
      (P<0.01) and dibutyryl cGMP, an activator of cGMP-dependent protein kinase,
      significantly attenuated the inhibition by L-NAME (P<0.01). Unstimulated and FMLP
      stimulated MA-NOS activity in LAgP neutrophils was statistically significantly
      higher than that in normal neutrophils (P<0.05). S-NOS activity in LAgP
      neutrophils was higher than that in normal neutrophils. CONCLUSIONS: This study
      suggests that NOS is present in human neutrophils and may be involved in FMLP
      induced chemotaxis in normal neutrophils. NOS activity is increased in LAgP and
      is negatively correlated to chemotaxis response.

PMID- 11525438
TI  - Short-chain carboxylic acids produced by gram-negative anaerobic bacteria can
      accelerate or delay polymorphonuclear leukocyte apoptosis in vitro.
AB  - BACKGROUND: Short-chain carboxylic acids (SCCA) are metabolic byproducts of
      anaerobic subgingival bacteria associated with human periodontal disease. We
      examined the effect of 4 SCCA (butyric, propionic, succinic, and lactic acids) on
      human polymorphonuclear leukocyte (PMN) apoptosis over the range of
      concentrations (1 to 30 mM) found in the diseased periodontium. METHODS: PMN
      suspensions were incubated at 37 degrees C with medium alone (control) or one of
      the 4 SCCA at concentrations of 1, 5, or 30 mM. Aliquots were withdrawn hourly to
      assess apoptosis and viability by fluorescence microscopy. RESULTS: Relative to
      untreated controls, PMN incubated for at least 5 hours with 1 mM butyric or
      propionic acids exhibited significant delays in apoptosis (P<0.05), while those
      incubated with succinic or lactic acids exhibited no significant differences from
      controls (P>0.05). At a concentration of 5 mM, propionic, succinic, and lactic
      acids had little effect on apoptosis (P>0.05), but butyric acid significantly
      accelerated apoptotic changes (P<0.05). At 30 mM, all SCCA except lactic acid
      significantly accelerated apoptosis (P<0.05). Incubation with SCCA did not
      adversely affect cell viability (typically >98%). Lysates from PMN incubated 6
      hours with 30 mM butyric or propionic acids contained significantly more caspase
      3 activity than lysates from untreated control PMN (P<0.05). Moreover,
      pretreatment with a specific inhibitor of caspase-3 blocked acceleration of PMN
      apoptosis by butyric or propionic acids (P<0.05). CONCLUSION: Low concentrations
      of butyric or propionic acids delay PMN apoptosis and extend their functional
      lifespan, while higher concentrations accelerate apoptosis through a mechanism
      that appears to involve caspase-3.

PMID- 11525440
TI  - A combination of a chemically modified doxycycline and a bisphosphonate
      synergistically inhibits endotoxin-induced periodontal breakdown in rats.
AB  - BACKGROUND: Chemically modified non-antimicrobial tetracyclines (CMTs) have been
      shown to inhibit pathologically elevated collagenase (and other matrix
      metalloproteinase, MMP) activity and bone resorption in vivo and in vitro.
      METHODS: In the current study, suboptimal doses of CMT-8 (a non-antimicrobial
      chemically modified doxycycline) and a bisphosphonate (clodronate, an anti-bone
      resorption compound) were administered daily, either as a single agent or as a
      combination therapy, to rats with experimental periodontitis induced by repeated
      injection of bacterial endotoxin (LPS) into the gingiva. At the end of the 1-week
      protocol, the gingival tissues were dissected, extracted, and the extracts
      analyzed for MMPs (collagenases and gelatinases) and for elastase, and the
      defleshed jaws were morphometrically analyzed for alveolar bone loss. RESULTS:
      LPS injection significantly (P<0.001) increased alveolar bone loss and increased
      collagenase (MMP-8), gelatinase (MMP-9), and elastase activities. Treatment of
      the LPS-injected rats with suboptimal CMT-8 alone or suboptimal clodronate alone
      produced slight reductions in the tissue-destructive proteinases and no
      significant reductions in alveolar bone loss. However, a combination of
      suboptimal CMT-8 and clodronate "normalized" the pathologically elevated levels
      of MMPs, elastase, and alveolar bone loss, indicating synergistic inhibition of
      tissue breakdown in this animal model of periodontitis. CONCLUSIONS: Combination
      of a CMT and a bisphosphonate may be a useful treatment to optimally suppress
      periodontal destruction and tooth loss and in other tissue-destructive
      inflammatory diseases such as arthritis.

PMID- 11525439
TI  - The osteoinductive potential of demineralized freeze-dried bone allograft in
      human non-orthotopic sites: a pilot study.
AB  - BACKGROUND: The use of demineralized freeze-dried bone allograft (DFDBA) in
      periodontal therapy is widely accepted. In addition to histologic studies
      demonstrating its role in regenerating the attachment apparatus, its recognized
      ability to exhibit osteoinduction in small laboratory mammals has prompted many
      clinicians to regard it as osteoinductive when utilized in periodontal therapy.
      Despite such a theoretical deduction, evaluating and establishing the
      osteoinductive potential of DFDBA in humans has been problematic. The purpose of
      this study was to investigate, through the use of a novel implantation/recovery
      model, the potential of DFDBA to induce new bone formation at sites not normally
      considered capable of de novo osteogenic activity. METHODS: Seven patients
      scheduled to undergo periodontal therapy utilizing non-absorbable membranes
      agreed to have sterile polypropylene mesh capsules placed adjacent to the primary
      surgical site for the purpose of this investigation. One capsule was left empty
      while the second capsule contained DFDBA. At the appropriate time interval for
      removal of the therapeutic membrane, the capsules were removed and submitted for
      histologic analysis. Five of the subjects had procedures directed at regenerating
      bone within molar furcations (guided tissue regeneration) and had the membranes
      and associated capsules removed between 6 and 8 weeks. The 2 remaining patients
      had procedures directed toward ridge augmentation (guided bone regeneration) and
      had the membranes removed either at 8 or 9 months, respectively. In addition, one
      of the 2 long-term membrane patients had liberal cortical penetration performed
      directly beneath the implanted capsule. RESULTS: Histologic analysis of all
      recovered capsules by 2 independent oral and maxillofacial pathologists could not
      confirm the presence of either osteoblastic or osteoclastic activity associated
      with the DFDBA particles, although the 2 longer-term specimens clearly exhibited
      trace amounts of vital bone non-contiguous with the implanted material.
      CONCLUSIONS: The results of this pilot study do not support the osteoinductive
      potential of DFDBA when utilized in quantities normally associated with
      periodontal bone grafting, although they do support the use of this
      implantation/recovery model to study other preparations and mechanisms of bone
      formation.

PMID- 11525441
TI  - Nifedipine induces gingival overgrowth in rats through a reduction in collagen
      phagocytosis by gingival fibroblasts.
AB  - BACKGROUND: Nifedipine is used as a long-acting vasodilator, and a primary side
      effect is the induction of gingival overgrowth, which is characterized by an
      accumulation of collagenous components within the gingival connective tissue. To
      elucidate the mechanisms of nifedipine-induced gingival overgrowth, we
      investigated the effect of nifedipine on Type I collagen metabolism in the
      gingiva of rats. METHODS: Twenty-day-old rats were fed a powdered diet containing
      or lacking nifedipine for 3 to 55 days. Immunohistochemical analysis with anti
      Type I collagen antibody was employed to examine the density of Type I collagen
      in the gingival connective tissue. Total RNAs were isolated from mandibular molar
      gingiva on days 0, 3, 15, 30, and 55, and reverse transcription polymerase chain
      reaction was performed to investigate the mRNA levels of Type I collagen. In
      addition, we performed a flow cytometric analysis with collagen-coated latex
      beads and cultured fibroblasts derived from rat gingiva to measure collagen
      phagocytosis. RESULTS: Immunohistochemical analysis revealed that Type I collagen
      was more prevalent in the connective tissue of nifedipine-treated gingiva than in
      controls on day 55. In the nifedipine-treated group, the expression of Type I
      collagen mRNA gradually decreased to 1.5% on day 55 compared to day 0. In the
      control group, Type I collagen mRNA also decreased to 32%; however, mRNA
      expression was significantly lower in the nifedipine-treated group than in the
      controls. When the rate of phagocytic cells derived from nifedipine-treated
      gingiva and controls was represented as the mean +/- SE of the percentage from 3
      different experiments, the values were as follows: on day 15, 13.5 +/- 2.1% and
      15.0 +/- 1.5%; on day 30, 12.2 +/- 4.3% and 34.5 +/- 6.7% in the nifedipine
      treated and the control group, respectively, indicating that phagocytic cells
      were considerably fewer in the nifedipine-treated gingiva on day 30. This finding
      demonstrates that the decrease in phagocytosis caused by nifedipine appeared
      before the detection of severe macroscopic gingival overgrowth. CONCLUSION: These
      findings suggest that the decrease in collagen degradation due to lower
      phagocytosis is closely associated with the increase in Type I collagen
      accumulation in nifedipine-treated rat gingiva.

PMID- 11525443
TI  - Subperiosteal connective tissue grafts for pocket reduction and preservation of
      gingival esthetics: a case report.
AB  - BACKGROUND: Clinical studies and recent histological evidence following
      mucogingival surgery for the treatment of gingival recession have documented that
      when closely adapted to a previously exposed root surface, connective tissue is
      capable of forming a new attachment. Despite these findings, no clinical tests
      have been conducted to examine the ability of connective tissue to reduce probing
      depth (PD) and increase clinical attachment levels (CAL) when it is implanted
      into periodontal osseous defects. The purpose of this paper is to report the
      clinical results on a patient following 2 subperiosteal connective tissue grafts.
      METHODS: Subperiosteal connective tissue grafts were placed in 2 sites of
      periodontal bone loss and deep pocketing in one patient. Following flap
      reflection and root preparation, a connective tissue graft 1.5 to 2.0 mm in
      thickness was draped and sutured over each osseous defect and then completely
      covered by the external flap. RESULTS: Ten months following subperiosteal
      connective tissue grafting, tooth #7 had 4 mm of CAL gain. Tooth #10 had 3 mm of
      CAL gain 8 months postoperatively. Both teeth had 1 mm gain in gingival
      recession. Both teeth probed 3 mm postoperatively. CONCLUSIONS: When connective
      tissue was grafted into 2 periodontal osseous defects, there were significant
      reductions in probing depth and gains in CAL. There was minimal postoperative
      gingival recession. The new clinical attachment gain remained stable for 8 to 10
      months following subperiosteal connective tissue grafting.

PMID- 11525442
TI  - Failure of resin ionomers in the retention of multi-rooted teeth with Class III
      furcation involvement: a rebuttal case report.
AB  - BACKGROUND: Severe periodontal furcation invasion has long been a treatment
      dilemma for the clinician. Many techniques have been advocated in the treatment
      of multi-rooted posterior teeth ranging from conventional scaling and root
      planing (SRP), apically positioned flaps, root amputations, root resections,
      tunnel procedures, guided tissue regeneration, and restorations. The keys to
      success depend on the clinician's ability to access the furcation to remove local
      factors and create an environment that enhances the patient's own hygiene
      efforts. Long-term success in treating teeth with furcation invasion depends upon
      tooth retention and arresting the destructive processes within the furcation
      area. METHODS: A Class III furcation invasion in a mandibular molar was treated
      by surgical access for SRP along with obliterating the furcation utilizing a
      resin ionomer restoration. RESULTS: Initially, the patient was asymptomatic.
      Within 3 months of treatment, the patient presented with suppuration that was
      refractory to local efforts. Radiographs taken only 5 months postsurgery
      demonstrated advanced bone loss apical to the restoration. The tooth ultimately
      was extracted because mobility increased and the tooth became symptomatic.
      CONCLUSIONS: The clinician must consider the multi-factorial etiology of
      periodontal breakdown within a furcation. For this patient, the technique of
      sealing off the exposed furcation with restorative material appeared to have
      resulted in progressive bone loss and accelerate tooth loss. This single case
      report is presented as a rebuttal to recently published articles, which have
      demonstrated excellent results when treating furcations with ionomer
      restorations.

PMID- 11525444
TI  - Oral focal mucinosis of the gingiva: case report.
AB  - BACKGROUND: Oral focal mucinosis is a rare disease of unknown etiology, where the
      connective tissue undergoes a focal myxoid degeneration. METHODS: We describe a
      48-year-old patient who was referred for a firm, tender mass located on the
      gingiva of the left central mandibular incisor. The first clinical impression at
      examination was that of a periodontal abscess. RESULTS: The lesion underwent a
      biopsy, and the final microscopic diagnosis was oral focal mucinosis.
      CONCLUSIONS: It must be stressed that in most focal gingival lesions, a
      preoperative diagnosis can be almost impossible.

PMID- 11525445
TI  - Root coverage of a palatal recession defect: a case report.
AB  - BACKGROUND: Obtaining predictable root coverage has become an important part of
      periodontal therapy. However, little has been reported concerning the treatment
      of palatal recession defects. This is a case report which demonstrates a
      technique to obtain root coverage of a palatal recession defect. METHODS: The
      technique involved elevating a partial-thickness palatal flap and placing a
      connective tissue graft beneath the flap and over the recession defect
      (subepithelial graft). The portion of the connective tissue graft placed over the
      recession defect was not covered by the flap. RESULTS: Clinically significant
      amounts of root coverage were obtained (84.6%), although the connective tissue
      graft was not covered by the flap. CONCLUSION: Root coverage of a palatal
      recession defect can be obtained with a subepithelial graft.

PMID- 11525446
TI  - Patient preference for light-cured composite bite splint compared to heat-cured
      acrylic bite splint.
AB  - BACKGROUND: Heat-cured acrylic has been the most commonly used material for
      construction of bite splints. Although effective, its processing involves several
      steps and is time consuming. Furthermore, acrylic splints distort easily if not
      kept in water when not worn for long periods of time. A newly developed light
      cured composite material is now being used for bite splint fabrication. The
      composite material offers benefits in ease and speed of construction, has minimal
      warping and distortion, and has proven patient acceptance. The aim of this study
      was to determine if patient satisfaction with the composite splint was as good
      as, or preferential to, the acrylic splint. METHODS: Both a composite and an
      acrylic bite splint were fabricated for each of 10 patients. The splints were
      worn alternately on a nightly basis and were adjusted as needed after the first
      week. After 3 weeks, each patient completed a questionnaire regarding the
      properties of each splint and any preferences they had in reference to fit,
      comfort, and other parameters of satisfaction. RESULTS: All of the patients were
      able to wear at least one of the splints comfortably. All 10 preferred the
      composite splint over the acrylic splint, agreeing that it felt more natural and
      was more comfortable to wear. CONCLUSIONS: The light-cured composite bite splint
      is preferable from the patient's perspective to the heat-cured acrylic bite
      splint. The composite splint is rapidly constructed on the original model, easily
      seated, and comfortably worn. Other properties of composite material also make it
      preferable for long-term use. Future studies are necessary to evaluate the
      functional differences between the composite and acrylic splint.

PMID- 11525447
TI  - A comparison of the success of root resected molars and molar position implants
      in function in a private practice: results of up to 15-plus years.
AB  - BACKGROUND: When faced with a furcated molar, today's clinician must decide
      between a number of treatment options, including root resection, tooth removal,
      and implant placement. This paper assesses the results in one private clinical
      practice of root resection and subsequent restoration or molar implant placement
      and subsequent restoration. Clinical considerations in treatment selection are
      discussed. METHODS: A retrospective analysis of treated patients was carried out
      by examining active and inactive patient charts. When patients had discontinued
      therapy, every effort was made to determine the reason for leaving the private
      practice, so as to assess the impact of previously undocumented treatment failure
      on the statistics in question. RESULTS: A total 701 root resected molars and
      1,472 molar implants were evaluated after > or = 15 and 13 years in function,
      respectively. Resection of the distal root of a mandibular molar demonstrated the
      lowest success rate (75%). All other success rates for various root resected
      molars in function ranged from 95.2% to 100%. Lone standing implants in second
      molar positions demonstrated the lowest success rate (85%). All other implant use
      in molar positions demonstrated a success rate ranging from 97.0% to 98.6%. Root
      resected molars and molar implants demonstrated the highest degree of failure
      when they were lone standing terminal abutments. Seven out of 23 (30.4%) root
      resected molar failures, and 17 of 45 (37.8%) of the molar implant failures were
      associated with untreated parafunction. Cumulative success rates were 96.8% for
      root resected molars and 97.0% for molar implants. Success and failure are
      discussed by tooth and/or implant position, and resected root, where applicable.
      Possible ramifications of these findings upon treatment planning are also
      reviewed. CONCLUSIONS: Both molar root resection and appropriate restoration and
      molar implant placement and restoration demonstrated a high degree of success in
      function. However, this success rate is markedly affected when either the root
      resected molar or molar implant is a lone standing terminal abutment. Care must
      be taken to choose the appropriate treatment modality for a given patient
      scenario.

PMID- 11525448
TI  - Reflections on Sigurd P. Ramfjord: his contributions to evidence-based
      periodontics.

PMID- 11525449
TI  - Osseointegrated implants in patients treated for generalized chronic
      periodontitis and generalized aggressive periodontitis: 3- and 5-year results of
      a prospective long-term study.
AB  - BACKGROUND: The successful use of osseointegrated implants in periodontally
      healthy patients has been documented in numerous longitudinal studies in recent
      years. However, the extent to which these positive results apply to periodontally
      diseased patients remains unclear. The aim of the present prospective
      longitudinal study of partially edentulous patients treated for generalized
      chronic periodontitis and generalized aggressive periodontitis was a clinical,
      microbiological, and radiographic comparison of teeth and implants and assessment
      of the implant success rate. METHODS: Five partially edentulous patients treated
      for generalized aggressive periodontitis (GAgP) and 5 treated for generalized
      chronic periodontitis (GCP) were enrolled in this study. The GAgP patients
      received 36 implants, and the GCP patients 12 implants. The teeth were examined 2
      to 4 weeks before extraction of the non-retainable teeth (baseline), and 3 weeks
      after insertion of the final abutments (second examination). All further
      examinations were performed during a 3-month recall schedule over a 5-year period
      for the GAgP patients and over a 3-year period for the GCP patients. At each
      session clinical parameters were recorded at teeth and implants and the
      composition of the subgingival microflora was determined by dark-field microscopy
      and DNA analysis. Intraoral radiographs of the teeth and implants were taken for
      control purposes at baseline; after insertion of the superstructure; and 1, 3,
      and 5 years later. RESULTS: The clinical findings indicated healthy periodontal
      and peri-implant conditions in both patient groups throughout the study. However,
      an increased probing depth and an attachment loss were recorded in the GAgP
      patients after the third year (P<0.001). The distribution of the microorganisms
      revealed no significant differences between the patient groups or between
      implants and teeth. Moderate bone loss at teeth and implants was registered in
      both groups. The success rates recorded were 100% in the GCP patients and 88.8%
      (maxilla: 85.7%; mandible: 93.3%) in the GAgP patients. CONCLUSIONS: The 3-year
      and 5-year follow-ups show that osseointegrated implants may be successful in
      oral rehabilitation of partially edentulous patients treated for generalized
      aggressive periodontitis and generalized chronic periodontitis. However, as no
      significant differences were recorded between conditions at teeth and at
      implants, progression of the disease cannot be ruled out.

PMID- 11525450
TI  - Clinical evaluation of acellular allograft dermis for the treatment of human
      gingival recession.
AB  - BACKGROUND: Periodontal root coverage procedures to treat recession areas are
      indicated for unesthetic, exposed, and/or painful root surfaces. Many methods,
      most using autogenous soft tissue grafts, have been utilized, but with associated
      morbidity at the donor sites. An alternative donor material would reduce the
      morbidity and provide for sufficient available donor tissue. METHODS: An
      acellular allogeneic dermal connective tissue matrix (AD) and autogenous palatal
      connective tissue (CT) were compared as subepithelial grafts for the treatment of
      gingival recession. Twenty-two patients with similar isolated gingival recession
      of > or = 2 mm on 2 separate teeth were treated with the subepithelial graft
      technique. Exposed roots were hand root planed only and, by random allocation,
      either a fitted AD or fitted CT graft was secured in place and covered by
      coronally positioned flaps. RESULTS: Mann Whitney U test analysis found the
      following changes at 6 months for AD and CT, respectively, compared to
      presurgical conditions: root coverage of 1.7 +/- 1.2 (65.9%) and 2.2 +/- 1.1 mm
      (74.1%) (both P<0.01), increase in keratinized tissue (KT) of 1.2 +/- 1.3 and 1.6
      +/- 1.9 (both P<0.01), and an increase in gingival thickness with both; 83.2% of
      expected root coverage was obtained with AD and 88.6% with CT (P= 0.43). There
      were no significant differences between treatments for any parameter. Global
      assessments by clinicians and patients suggested a more esthetic clinical result
      with AD. CONCLUSIONS: These results suggest that acellular allogeneic dermal
      matrix may be a useful substitute for autogenous connective tissue grafts in root
      coverage procedures.

PMID- 11525451
TI  - Osteoporosis prevention, diagnosis, and therapy.
AB  - OBJECTIVE: The objective of this NIH Consensus Statement is to inform the
      biomedical research and clinical practice communities of the results of the NIH
      Consensus Development Conference on Osteoporosis Prevention, Diagnosis, and
      Therapy. The statement provides state-of-the-art information and presents the
      conclusions and recommendations of the consensus panel regarding these issues. In
      addition, the statement identifies those areas of study that deserve further
      investigation. The target audience of clinicians for this statement includes, but
      is not limited to, family practitioners, internists, gerontologists, orthopaedic
      surgeons, rheumatologists, obstetricians and gynecologists, and preventive
      medicine specialisits. PARTICIPANTS: A nonfederal, nonadvocate, 13-member panel
      representing the fields of internal medicine, family and community medicine,
      endocrinology, epidemiology, orthopaedic surgery, gerontology, rheumatology,
      obstetrics and gynecology, preventive medicine, and cell biology. In addition, 32
      experts from these same fields presented data to the panel and a conference
      audience of approximately 700. EVIDENCE: The literature was searched using
      MEDLINE and an extensive bibliography of references was provided to the panel.
      Experts prepared abstracts for their conference presentations with relevant
      citations from the literature. Scientific evidence was given precedence over
      clinical anecdotal experience. CONSENSUS PROCESS: The panel, answering predefined
      questions, developed their conclusions based on the scientific evidence presented
      in open forum and the scientific literature. The panel composed a draft
      statement, which was read in its entirety and circulated to the experts and the
      audience for comment. Thereafter, the panel resolved conflicting recommendations
      and released a revised statement at the end of the conference. The panel
      finalized the revisions within a few weeks after the conference. The draft
      statement was made available on the World Wide Web immediately following its
      release at the conference and was updated with the panel's final revisions.
      CONCLUSIONS: Osteoporosis occurs in all populations and at all ages. Though more
      prevalent in white postmenopausal females, it often goes unrecognized in other
      populations. Osteoporosis is a devastating disorder with significant physical,
      psychosocial, and financial consequences. The risks for osteoporosis, as
      reflected by low bone density, and the risks for fracture overlap but are not
      identical. More attention should be paid to skeletal health in persons with
      conditions known to be associated with secondary osteoporosis. Clinical risk
      factors have an important, but as yet poorly validated, role in determining who
      should have BMD measurement, in assessing risk of fracture, and in determining
      who should be treated. Adequate calcium and vitamin D intake are crucial to
      develop optimal peak bone mass and to preserve bone mass throughout life.
      Supplementation of these two components in bioavailable forms may be necessary in
      individuals who do not achieve recommended intake from dietary sources. Gonadal
      steroids are important determinants of peak and lifetime bone mass in men, women,
      and children. Regular exercise, especially resistance and high-impact activities,
      contributes to development of high peak bone mass and may reduce the risk of
      falls in older individuals. Assessment of bone mass, identification of fracture
      risk, and determination of who should be treated are the optimal goals when
      evaluating patients for osteoporosis. Fracture prevention is the primary goal in
      the treatment of patients with osteoporosis. Several treatments have been shown
      to reduce the risk of osteoporotic fractures. These include therapies that
      enhance bone mass and reduce risk or consequences of falls. Adults with
      vertebral, rib, hip, or distal forearm fractures should be evaluated for the
      presence of osteoporosis and given appropriate therapy.

PMID- 11525452
TI  - Perspective: Evolution of flower color in the desert annual Linanthus parryae:
      Wright revisited.
AB  - Linanthus parryae, a diminutive desert annual with white or blue flowers, has
      been the focus of a long-standing debate among evolutionary biologists. At issue
      is whether the flower color polymorphism in this species is the product of random
      genetic drift, as Sewall Wright argued, or of natural selection, as proposed by
      Carl Epling and his colleagues. Our long-term studies of three polymorphic
      populations in the Mojave Desert demonstrate that flower color is subject to
      selection that varies in both time and space in its direction and magnitude. For
      all sites taken together, blue-flowered plants produced more seeds than white
      flowered plants in years of relatively low seed production, whereas white
      flowered plants had higher fitness in years of high seed production. Evidence of
      selection on flower color was found in two of the three study sites. Differences
      in fitness between the color morphs were sometimes large, with selection
      coefficients as high as 0.60 in some years. Our longest period of observations
      was at Pearblossom site 1, where plants reached appreciable densities in seven of
      the 11 years of study. Here we found significant differences in the seed
      production of the color morphs in six years, with three years of blue advantage
      and three years of white advantage. For all sites taken together, total spring
      precipitation (March and April) was positively correlated with both absolute and
      relative seed production of the color morphs. At Pearblossom site 1, blue
      flowered plants typically had a fitness advantage in years of low spring
      precipitation, whereas white-flowered plants had a fitness advantage in years of
      high spring precipitation. This temporal variation in selection may contribute to
      the maintenance of the flower-color polymorphism at Pearblossom site 1, whereas
      gene flow from neighboring populations is proposed as the principal factor
      maintaining the polymorphism at the other study sites. We found no significant
      differences between the color morphs in pollinator visitation rate or in their
      carbon isotope ratio, a measure of water-use efficiency. Although the mechanism
      of selection remains elusive, our results refute Wright's conclusion that the
      flower color polymorphism in L. parryae is an example of isolation by distance, a
      key component of his shifting balance theory of evolution.

PMID- 11525453
TI  - Stable two-allele polymorphisms maintained by fluctuating fitnesses and seed
      banks: protecting the blues in Linanthus parryae.
AB  - Motivated by data demonstrating fluctuating relative and absolute fitnesses for
      white- versus blue-flowered morphs of the desert annual Linanthus parryae, we
      present conditions under which temporally fluctuating selection and fluctuating
      contributions to a persistent seed bank will maintain a stable single-locus
      polymorphism. In L. parryae, blue flower color is determined by a single dominant
      allele. To disentangle the underlying diversity-maintaining mechanism from the
      mathematical complications associated with departures from Hardy-Weinberg
      genotype frequencies and dominance, we successively analyze a haploid model, a
      diploid model with three distinguishable genotypes, and a diploid model with
      complete dominance. For each model, we present conditions for the maintenance of
      a stable polymorphism, then use a diffusion approximation to describe the long
      term fluctuations associated with these polymorphisms. Our protected polymorphism
      analyses show that a genotype whose arithmetic and geometric mean relative
      fitnesses are both less than one can persist if its relative fitness exceeds one
      in years that produce the most offspring. This condition is met by data from a
      population of L. parryae whose white morph has higher fitness (seed set) only in
      years of relatively heavy rain fall. The data suggest that the observed
      polymorphism may be explained by fluctuating selection. However, the yearly
      variation in flower color frequencies cannot be fully explained by our simple
      models, which ignore age structure and possible selection in the seed bank. We
      address two additional questions--one mathematical, the other biological-
      concerning the applicability of diffusion approximations to intense selection and
      the applicability of long-term predictions to datasets spanning decades for
      populations with long-lived seed banks.

PMID- 11525454
TI  - Meiotic recombination, cross-reactivity, and persistence in Plasmodium
      falciparum.
AB  - We incorporate a representation of Plasmodium falciparum recombination within a
      discrete-event model of malaria transmission. We simulate the introduction of a
      new parasite genotype into a human population in which another genotype has
      reached equilibrium prevalence and compare the emergence and persistence of the
      novel recombinant forms under differing cross-reactivity relationships between
      the genotypes. Cross-reactivity between the parental (initial and introduced)
      genotypes reduces the frequency of appearance of recombinants within three years
      of introduction from 100% to 14%, and delays their appearance by more than a
      year, on average. Cross-reactivity between parental and recombinant genotypes
      reduces the frequency of appearance to 36% and increases the probability of
      recombinant extinction following appearance from 0% to 83%. When a recombinant is
      cross-reactive with its parental types, its probability of extinction is
      influenced by cross-reactivity between the parental types in the opposite manner;
      that is, its probability of extinction after appearance decreases. Frequencies of
      P. falciparum outcrossing are mediated by frequencies of mixed-genotype
      infections in the host population, which are in turn mediated by the structure of
      cross-reactivity between parasite genotypes. The three leading hypotheses about
      how meiosis relates to oocyst production lead to quantitative, but no
      qualitative, differences in these results.

PMID- 11525455
TI  - Disease diversity and human fertility.
AB  - The existence of parasitic constraints on the evolution of life-history traits in
      free-living organisms has been demonstrated in several plant and animal species.
      However, the association between different diseases and human traits is virtually
      unknown. We conducted a comparative analysis on a global scale to test whether
      the diversity of human diseases, some of them responsible for high incidences of
      morbidity and mortality, were associated with host life-history characteristics.
      After controlling for direct confounding effects exerted by historical, spatial,
      economic, and population patterns and their interactions, our findings show that
      human fertility increases with the diversity and structure of disease types.
      Thus, disease control may not only lower the costs associated with morbidity, but
      could also contribute directly or indirectly to reductions in human population
      growth.

PMID- 11525456
TI  - Melastomeae come full circle: biogeographic reconstruction and molecular clock
      dating.
AB  - Rhexia, with 11 species in the Coastal Plain province of North America, is the
      only temperate zone endemic of the tropical eudicot family Melastomataceae. It is
      a member of the only pantropical tribe of that family, Melastomeae. Based on the
      chloroplast gene ndhF, we use a fossil-calibrated molecular clock to address the
      question of the geographic origin and age of Rhexia. Sequences from 37 species in
      21 genera representing the tribe's geographical range were analyzed together with
      five outgroups. To obtain better clade support, another chloroplast region, the
      rpl16 intron, was added for 24 of the species. Parsimony analysis of the combined
      data and maximum-likelihood analysis of ndhF alone indicate that the deepest
      split is between Rhexia plus its sister group, a small Central American genus,
      and all other Melastomeae. Old World Melastomeae are monophyletic and nested
      within New World Melastomeae. Although likelihood-ratio tests of clock and
      nonclock substitution models for the full or moderately pruned datasets rejected
      the clock, these models yielded identical topologies (for 30 taxa) with few
      significantly different branch lengths as assessed by a Student's t-test. Age
      estimates obtained were 22 million years ago (Mya) for the divergence of Rhexia
      from its sister group, 12 Mya for the dispersal of Melastomeae from the New World
      to West Africa, and 1 Mya for the diversification of Melastoma in Southeast Asia.
      The only other genus of Melastomeae to have reached Southeast Asia from Africa or
      Madagascar is Osbeckia. The age and geographic distribution of fossils, which
      come from Miocene sites throughout Eurasia, suggest that Melastomeae once ranged
      from Eurasia across Beringia to North America from whence they reached South
      America and subsequently Africa and Southeast Asia. Climate deterioration led to
      their extinction in the Northern Hemisphere, with Rhexia possibly surviving in
      Coastal Plain refugia.

PMID- 11525457
TI  - Hybrid populations selectively filter gene introgression between species.
AB  - Hybrids have long been recognized as a potential pathway for gene flow between
      species that can have important consequences for evolution and conservation
      biology. However, few studies have demonstrated that genes from one species can
      introgress or invade another species over a broad geographic area. Using 35
      genetically mapped restriction fragment length polymorphism (RFLP) markers of two
      species of cottonwoods (Populus fremontii x P. angustifolia) and their hybrids (n
      = 550 trees), we showed that the majority of the genome is prohibited from
      introgressing from one species into the other. However, this barrier was not
      absolute; Fremont cpDNA and mtDNA were found throughout the geographic range of
      narrowleaf cottonwood, and 20% of the nuclear markers of Fremont cottonwood
      introgressed varying distances (some over 100 km) into the recipient species'
      range. Rates of nuclear introgression were variable, but two nuclear markers
      introgressed as fast as the haploid, cytoplasmically inherited chloroplast and
      mitochondrial markers. Our genome-wide analysis provides evidence for positive,
      negative, and neutral effects of introgression. For example, we predict that DNA
      fragments that introgress through several generations of backcrossing will be
      small, because small fragments are less likely to contain deleterious genes.
      These results argue that recombination will be important, that introgression can
      be very selective, and that evolutionary forces within the hybrid population to
      effectively "filter" gene flow between species. A strong filter may make
      introgression adaptive, prevent genetic assimilation, lead to relaxed isolating
      mechanisms, and contribute to the stability of hybrid zones. Thus, rather than
      hybridization being a negative factor as is commonly argued, natural
      hybridization between native species may provide important genetic variation that
      impacts both ecological and evolutionary processes. Finally, we propose two
      hypotheses that contrast the likelihood of contemporary versus ancient
      introgression in this system.

PMID- 11525458
TI  - Adaptive maintenance of genetic polymorphism in an intertidal barnacle: habitat-
      and life-stage-specific survivorship of Mpi genotypes.
AB  - In the northern acorn barnacle, Semibalanus balanoides, genotype frequencies of
      three genetic markers were tracked over time in four types of intertidal
      habitats. These habitats were selected to represent natural variation in several
      environmental parameters, specifically the degree of physical stress experienced
      by barnacles. Frequencies for one allozyme locus (Gpi) and a presumably neutral
      mtDNA marker were homogeneous among habitats in each temporal sample. Similarly,
      no temporal stratification in genotype frequencies was evident across the five
      sampling intervals: from planktonic larvae sampled in March to juveniles
      collected at the end of June. In contrast to the Gpi and mtDNA loci, Mpi
      genotypes significantly changed in frequency in two habitats in the high
      intertidal zone. On exposed substrate, the Mpi-FF homozygote increased in
      frequency, whereas the alternative homozygote, Mpi-SS, significantly decreased in
      frequency. Barnacles that were protected from environmental stress at high
      intertidal heights by the Ascophyllum nodosum algal canopy demonstrated the
      opposite pattern. In both habitats, the change in frequency of the heterozygote
      was intermediate to that of the homozygous genotypes. Furthermore, these patterns
      of genotype-by-environment association reflected a pulse of genotype-specific
      mortality that occurred over a two-week interval subsequent to metamorphosis from
      the larval to the adult form. These data indicate that each Mpi homozygote is the
      highest fitness genotype in some portion of the intertidal environment. Using the
      Levene (1953) model to evaluate the spatial variation in genotypic fitness, the
      stable maintenance of the Mpi polymorphism is predicted under certain subsets of
      conditions. Environmental heterogeneity in the intertidal zone translates to
      spatial variation in selection pressures, which may result in the active
      maintenance of the Mpi polymorphism in this species.

PMID- 11525459
TI  - Grapes, galls, and geography: the distribution of nuclear and mitochondrial DNA
      variation across host-plant species and regions in a specialist herbivore.
AB  - Studies of patterns of molecular variation in natural populations can provide
      important insights into a number of evolutionary problems. Among these, the
      question of whether geographic factors are more important than ecological factors
      in promoting population differentiation and ultimately speciation has been an
      important and contentious area in evolutionary biology. Systems involving
      herbivorous insects have played a leading role in this discussion. This study
      examined the distribution of molecular variation in a highly specialized gall
      forming insect, grape phylloxera (Daktulosphaira vitifoliae Fitch), that is found
      on both sympatric and allopatric host-plant species of the genus Vitis. In
      addition, the relationship of insects in the introduced range in the United
      States to ancestral populations in the native range was examined. Evidence for
      differentiation along host-plant lines from both nuclear (RAPD) and mitochondrial
      (COI) DNA was confounded with the effect of geography. Differentiation was found
      where hosts were allopatric or parapatric, but no evidence was found for such
      differentiation on two hosts, V. vulpina and V. aestivalis, that are broadly
      sympatric. The question of population differentiation onto these sympatric hosts
      can be considered to be resolved--it has not occurred in spite of a long history
      of association. Evidence was equivocal, but suggestive of a period of divergence
      in allopatry prior to reestablishment of contact, for insects associated with
      another host plant species, V. cinerea, found in both sympatric and parapatric
      populations. A low level of diversity and placement of samples collected from the
      grape species V. riparia at the tip of a phylogenetic tree supports the
      hypothesis that this host has been recently colonized from populations from the
      Mississippi Valley. A polyphyletic origin for biotype B grape phylloxera was
      supported: Although most samples collected from vineyards in the introduced range
      in California had similar haplotypes, they were closely related to natives on V.
      vulpina from the Atlantic Coast-Piedmont region. All samples collected from
      vineyards in Oregon and Washington were closely related to natives on V. riparia
      in the northern United States.

PMID- 11525460
TI  - Correlated responses to selection for faster development and early reproduction
      in Drosophila: the evolution of larval traits.
AB  - Studies on selection for faster development in Drosophila have typically focused
      on the trade-offs among development time, adult weight, and adult life span.
      Relatively less attention has been paid to the evolution of preadult life stages
      and behaviors in response to such selection. We have earlier reported that four
      laboratory populations of D. melanogaster selected for faster development and
      early reproduction, relative to control populations, showed considerably reduced
      preadult development time and survivorship, dry weight at eclosion, and larval
      growth rates. Here we study the larval phase of these populations in greater
      detail. We show here that the reduction in development time after about 50
      generations of selection is due to reduced duration of the first and third larval
      instars and the pupal stage, whereas the duration of the second larval instar has
      not changed. About 90% of the preadult mortality in the selected populations is
      due to larval mortality. The third instar larvae, pupae, and freshly eclosed
      adults of the selected populations weigh significantly less than controls, and
      this difference appears during the third larval instar. Thereafter, percentage
      weight loss during the pupal stage does not differ between selected and control
      populations. The minimum amount of time a larva must feed to subsequently
      complete development is lower in the selected populations, which also exhibit a
      syndrome of reduced energy expenditure through reduction in larval feeding rate,
      larval digging and foraging activity, and pupation height. Comparison of these
      results with those observed earlier in populations selected for adaptation to
      larval crowding and faster development under a different protocol from ours
      reveal differences in the evolved traits that suggest that the responses to
      selection for faster development are greatly affected by the larval density at
      which selection acts and on details of the selection pressures acting on the
      timing of reproduction.

PMID- 11525461
TI  - Phylogenetic analysis of sexual dimorphism and eye-span allometry in stalk-eyed
      flies (Diopsidae).
AB  - Eye stalks and their scaling relationship with body size are important features
      in the mating system of many diopsid species, and sexual selection is a critical
      force influencing the evolution of this exaggerated morphology. Interspecific
      variation in eye span suggests there has been significant evolutionary change in
      this trait, but a robust phylogenetic hypothesis is required to determine its
      rate and direction of change. In this study, the pattern of morphological
      evolution of eye span is assessed in a phylogenetic framework with respect to its
      function in the sexual system of these flies. Specifically, we examine within the
      family Diopsidae the pattern of increase and decrease in sexual dimorphism, the
      morphological coevolution of eye span between males and females, and the
      evolutionary flexibility of eye-span allometry. Based on several different
      methods for reconstructing morphological change, results suggest a general
      pattern of evolutionary flexibility, particularly for eye-span allometry. Sexual
      dimorphism in eye span has evolved independently at least four times in the
      family and this trait also has undergone several reductions within the genus
      Diasemopsis. Despite most species being dimorphic, there is a strong phylogenetic
      correlation between males and females for mean eye span. The coevolution between
      the sexes for eye-span allometry, however, is significantly weaker. Overall, eye
      span allometry exhibits significantly more change on the phylogeny than the other
      morphological traits. The evolutionary pattern in eye-span allometry is caused
      primarily by changes in eye-span variance. Therefore, this pattern is consistent
      with recent models that predict a strong relationship between sexual selection
      and the variance of ornamental traits and highlights the significance of eye-span
      allometry in intersexual and intrasexual signaling.

PMID- 11525462
TI  - Geographic variation in female preference functions and male songs of the field
      cricket Teleogryllus oceanicus.
AB  - Male crickets (Teleogryllus oceanicus) produce a complex call consisting of two
      elements, the long chirp (three to eight sound pulses) followed by a series of
      short chirps (each with two sound pulses). There is significant geographic
      variation in the temporal structure of calls, and the long chirp is selected
      against by acoustically orienting parasitoids in some populations. Here we
      examine geographic variation in female preference functions for the amount of
      long chirp. In general, females prefer calls with greater proportions of long
      chirp, although the strength and nature of selection varied across populations.
      Variation in preference functions did not match variation in call structure.
      There was a mismatch between the proportion of long chirp produced by males in a
      population and the proportion of long chirp preferred by females. The convergent
      preferences of predators and females are likely to maintain genetic variation in
      song traits in parasitized populations. The apparent mismatch between preference
      and trait is discussed in relation to theoretical models of preference evolution.

PMID- 11525463
TI  - Phylogeography of the New Zealand cicada Maoricicada campbelli based on
      mitochondrial DNA sequences: ancient clades associated with cenozoic
      environmental change.
AB  - New Zealand's isolation, its well-studied rapidly changing landscape, and its
      many examples of rampant speciation make it an excellent location for studying
      the process of genetic differentiation. Using 1520 base pairs of mitochondrial
      DNA from the cytochrome oxidase subunit I, ATPase subunits 6 and 8 and tRNA(Asp)
      genes, we detected two well-differentiated, parapatrically distributed clades
      within the widespread New Zealand cicada species Maoricicada campbelli that may
      prove to represent two species. The situation that we uncovered is unusual in
      that an ancient lineage with low genetic diversity is surrounded on three sides
      by two recently diverged lineages. Using a relaxed molecular clock model coupled
      with Bayesian statistics, we dated the earliest divergence within M. campbelli at
      2.3 +/- 0.55 million years. Our data suggest that geological and climatological
      events of the late Pliocene divided a once-widespread species into northern and
      southern components and that near the middle of the Pleistocene the northern
      lineage began moving south eventually reaching the southern clade. The southern
      clade seems to have moved northward to only a limited extent. We discovered five
      potential zones of secondary contact through mountain passes that will be
      examined in future work. We predict that, as in North American periodical
      cicadas, contact between these highly differentiated lineages will exist but will
      not involve gene flow.

PMID- 11525464
TI  - Rapid evolution in the Nebria gregaria group (Coleoptera: Carabidae) and the
      paleogeography of the Queen Charlotte Islands.
AB  - Morphological differentiation in the ground beetles of the Nebria gregaria group,
      found on the Queen Charlotte Islands, has been used as support for the glacial
      refugium proposed for the northwest coast of North America. Two members of this
      species group, N. charlottae and N. louiseae, are restricted to cobble beaches in
      this archipelago. A third, N. haida, is found only in alpine regions of the
      archipelago and the adjacent mainland. The remaining two species of the gregaria
      group, N. lituyae and N. gregaria, show highly restricted distributions in the
      mountains of the Alaska panhandle and on the beaches of the Aleutian Islands,
      respectively. To determine the relationships of the five species, we conducted
      phylogenetic analyses on nucleotide sequence data obtained from five regions of
      the mitochondrial DNA. In total, 1835 bp were analyzed. The results suggest that
      one species, N. lituyae, does not belong in the gregaria group, and that only
      seven mutations separated the two most divergent of the four remaining species.
      We also conducted random amplified polymorphic DNA fingerprinting analyses on
      genomic DNA extracted from the five species. Analyses of genetic diversity
      revealed a lack of molecular differentiation among the Queen Charlotte species,
      suggesting that these populations may be postglacial in origin and that together
      N. gregaria, N. charlottae, N. louiseae, and N. haida might represent local
      variations of a single species. These results are consistent with conclusions
      derived for the morphological and genetical differentiation among Gasterosteus
      populations in the archipelago.

PMID- 11525465
TI  - Simplification as a trend in synapsid cranial evolution.
AB  - The prevalence and meaning of morphological trends in the fossil record have
      undergone renewed scrutiny in recent years. Studies have typically focused on
      trends in body size evolution, which have yielded conflicting results, and have
      only rarely addressed the question as to whether other morphological
      characteristics show persistent directionality over long time scales. I
      investigated reduction in number of skull and lower jaw bones (through loss or
      fusion) over approximately 150 million years of premammalian synapsid history.
      The results of a new skull simplification metric (SSM), which is defined as a
      function of the number of distinct elements, show that pronounced simplification
      is evident on both temporal (i.e., stratigraphic) and phylogenetic scales.
      Postcranial evolution exhibits a similar pattern. Skull size, in contrast, bears
      little relationship with the number of distinct skull bones present. Synapsid
      skulls carried close to their observed maximum number of elements for most of the
      Late Carboniferous and Early Permian. The SSM decreased in the Late Permian but,
      coincident with the radiation of early therapsids, the range of observed SSM
      values widened during this interval. From derived nonmammalian cynodonts in the
      Early Triassic through the earliest mammals in the Early Jurassic, both the
      minimum and maximum SSM decreased. Data from three representative modern mammals
      (platypus, opossum, and human) suggest that this trend continues through the
      Cenozoic. In a phylogenetic context, the number of skull elements present in a
      taxon shows a significant negative relationship with the number of branching
      events passed from the root of the tree; more deeply embedded taxa have smaller
      SSM scores. This relationship holds for various synapsid subgroups as well.
      Although commonly ascribed to the effects of long-term selection, evolutionary
      trends can alternatively reflect an underlying intrinsic bias in morphological
      change. In the case of synapsid skull bones (and those of some other tetrapods
      lineages), the rare production of novel, or neomorphic, elements may have
      contributed to the observed trend toward skeletal simplification.

PMID- 11525466
TI  - Sexual selection on plumage and behavior in an avian hybrid zone: experimental
      tests of male-male interactions.
AB  - In western Panama, an unusual hybrid zone exists between white-collared manakins,
      Manacus candei, and golden-collared manakins, M. vitellinus. Unidirectional
      introgression of plumage traits from vitellinus into candei has created a region
      in which all definitively plumaged males have a collar that is lemon-colored.
      These males are nearly indistinguishable from white-collared candei genetically
      and morphometrically, but strongly resemble golden-collared vitellinus due to the
      introgression of secondary sexual plumage traits, particularly the lemon-colored
      collar. The introgression could be explained by sexual selection for golden
      collared traits or by a series of mechanisms that do not invoke sexual selection
      (e.g., neutral diffusion, dominant allele). Sexual selection on male-male
      interactions implies behavioral differences among the plumage forms--specifically
      that golden- and lemon-collared males should be more aggressive than white
      collared males. In contrast, the nonsexual hypotheses predict behavioral
      similarity between lemon- and white-collared males, based on their nearly
      identical genetics. We tested the sexual selection hypothesis experimentally, by
      presenting males with taxidermic mounts of the three forms. As response
      variables, we monitored vocalizations and attacks on the mounts by replicate
      subject males. Both golden-collared and lemon-collared males were more likely to
      attack than were white-collared males, as predicted under sexual selection but
      not by the nonsexual hypotheses. Lemon-collared males were more vocally reactive
      than either parental form, contrary to the prediction of the nonsexual
      hypotheses. Our study demonstrates that sexual selection on male-male
      interactions may play an important role in the dynamics of character evolution
      and hybrid zones.

PMID- 11525467
TI  - Sexual selection of multiple handicaps in the red-collared widowbird: female
      choice of tail length but not carotenoid display.
AB  - Although sexual selection through female choice explains exaggerated male
      ornaments in many species, the evolution of the multicomponent nature of most
      sexual displays remains poorly understood. Theoretical models suggest that
      handicap signaling should converge on a single most informative quality
      indicator, whereas additional signals are more likely to be arbitrary Fisherian
      traits, amplifiers, or exploitations of receiver psychology. Male nuptial plumage
      in the highly polygynous red-collared widowbird (Euplectes ardens) comprises two
      of the commonly advocated quality advertisements (handicaps) in birds: a long
      graduated tail and red carotenoid coloration. Here we use multivariate selection
      analysis to investigate female choice in relation to male tail length, color
      (reflectance) of the collar, other aspects of morphology, ectoparasite load,
      display rate, and territory quality. The order and total number of active nests
      obtained are used as measures of male reproductive success. We demonstrate a
      strong female preference and net sexual selection for long tails, but marginal or
      no effects of color, morphology, or territory quality. Tail length explained 47%
      of male reproductive success, an unusually strong fitness effect of natural
      ornament variation. Fluctuating tail asymmetry was unrelated to tail length, and
      had no impact on mating success. For the red collar, there was negative net
      selection on collar area, presumably via its negative relationship with tail
      length. None of the color variables (hue, chroma, and brightness) had significant
      selection differentials, but a partial effect (selection gradient) of chroma
      might represent a color preference when tail length is controlled for. We suggest
      that the red collar functions in male agonistic interactions, which has been
      strongly supported by subsequent work. Thus, female choice targets only one
      handicap, extreme tail elongation, disregarding or even selecting against the
      carotenoid display. We discuss whether long tails might be better indicators of
      genetic quality than carotenoid pigmentation. As regards the evolution of
      multiple ornaments, we propose that multiple handicap signaling is stable not
      because of multiple messages but because of multiple receivers, in this case
      females and males.

PMID- 11525468
TI  - The evolution of body armor in mammals: plantigrade constraints of large body
      size.
AB  - Predictions associated with opposing selection generating minimum variance in
      basal metabolic rate (BMR) in mammals at a constrained body mass (CBM; 358 g)
      were tested. The CBM is presumed to be associated with energetic constraints
      linked to predation and variable resources at intermediate sizes on a logarithmic
      mass scale. Opposing selection is thought to occur in response to energetic
      constraints associated with predation and unpredictable resources. As body size
      approaches and exceeds the CBM, mammals face increasing risks of predation and
      daily energy requirements. Fast running speeds may require high BMRs, but
      unpredictable and low resources may select for low BMRs, which also reduce
      foraging time and distances and thus predation risks. If these two selection
      forces oppose each other persistently, minimum BMR variance may result. However,
      extreme BMR outliers at and close to the CBM should be indicative of unbalanced
      selection and predator avoidance alternatives (escapers vs. defenders), and may
      therefore provide indirect support for opposing selection. It was confirmed that
      body armor in defenders evolves at and above the CBM, and armored mammals had
      significantly lower BMRs than their nonarmored counterparts. However, analyses
      comparing the BMR of escapers--the fastest nonarmored runners (Lagomorpha)--with
      similar-sized counterparts were inconclusive and were confounded by limb
      morphology associated with speed optimization. These analyses suggest that the
      risks and costs of predation and the speed limitations of the plantigrade foot
      may constrain the evolution of large body sizes in plantigrade mammals.

PMID- 11525470
TI  - Adaptive life-history evolution in the livebearing fish Brachyrhaphis
      rhabdophora: genetic basis for parallel divergence in age and size at maturity
      and a test of predator-induced plasticity.
AB  - I document a genetic basis for parallel evolution of life-history phenotypes in
      the livebearing fish Brachyrhaphis rhabdophora from northwestern Costa Rica. In
      previous work, I showed that populations of B. rhabdophora that co-occur with
      predators attain maturity at smaller sizes than populations that live in predator
      free environments. I also demonstrated that this pattern of phenotypic divergence
      in life histories was independently repeated in at least five isolated drainages.
      However, life-history phenotypes measured from wild-caught fish could be
      attributed to environmental effects rather than to genetic differences among
      populations. In the present study, I reared male fish from four populations (two
      that co-occur with predators and two from predator-free environments) under four
      sets of environmental conditions. The pattern of phenotypic divergence in
      maturation size documented in the field between populations collected from
      different predation environments persisted after two generations in the
      laboratory. I also found a genetic basis for differences between populations in
      the age at which males attain maturity and in growth rates. By rearing fish in
      four different common environments, I tested for phenotypic plasticity in male
      life-history traits in response to nonlethal exposure to predators. There was a
      significant delay in the onset of sexual maturity in fish exposed to predators
      relative to those in the control, but no differences among treatments in size at
      maturity or growth rates. These results, coupled with previous work on B.
      rhabdophora, demonstrate a repeated pattern of parallel evolutionary divergence
      among genetically isolated populations that is strongly associated with
      predation.

PMID- 11525469
TI  - The accretion model of Neandertal evolution.
AB  - The Accretion model of Neandertal evolution specifies that this group of Late
      Pleistocene hominids evolved in partial or complete genetic isolation from the
      rest of humanity through the gradual accumulation of distinctive morphological
      traits in European populations. As they became more common, these traits also
      became less variable, according to those workers who developed the model. Its
      supporters propose that genetic drift caused this evolution, resulting from an
      initial small European population size and either complete isolation or drastic
      reduction in gene flow between this deme and contemporary human populations
      elsewhere. Here, we test an evolutionary model of gene flow between regions
      against fossil data from the European population of the Middle and Late
      Pleistocene. The results of the analysis clearly show that the European
      population was not significantly divergent from its contemporaries, even in a
      subset of traits chosen to show the maximum differences between Europeans and
      other populations. The pattern of changes, over time within Europe of the traits
      in this subset, does not support the Accretion model, either because the
      characters did not change in the manner specified by the model or because the
      characters did not change at all. From these data, we can conclude that special
      phenomena such as near-complete isolation of the European population during the
      Pleistocene are not required to explain the pattern of evolution in this region.

PMID- 11525471
TI  - An approach to assess level of satisfaction of the residents in relation to SWM
      system.
AB  - The issue of managing solid waste (SW), especially in the major cities, is of
      growing concern to the municipal organisations in India. The present performance
      of the system is recognised to be unsatisfactory. This paper delineates an
      approach to quantify the satisfaction level of the residents as a measure of
      performance of the system and also presents a case study in a major city. The
      results show the validity of the approach.

PMID- 11525472
TI  - Studies on the evaluation of municipal waste management systems.
AB  - The municipal waste disposal system is at a turning point now, because full-scale
      efforts are demanded to approach the goal of 'the construction of a waste
      recycling society'. An attempt was made to evaluate municipal solid waste
      management systems with easier indexes in the model area. This study includes two
      evaluation systems. One evaluation system (case 1) is based on the analysis of
      waste management costs. Different waste disposal systems can be easily evaluated
      by comparing the waste disposal costs associated with them. However, it seems
      risky to rate cities only by the results of an analysis of the waste disposal
      cost data, since the municipalities build, acquire or expand facilities
      independently from one another. The associated costs are not summed in a uniform
      way by all municipalities and for other reasons. The other evaluation system
      (case 2) is based on the 'amenity and comfort ranking of cities' (Keizai 1998).
      Judgment by one evaluation index alone for a waste disposal system seems risky
      since the data in that case are insufficient for proper evaluation of a city.
      Hence, it is desirable to use two or more indices representative of a future
      ideal system. The results of the study demonstrated that Toyo Keizai's method of
      'amenity and comfort ranking of cities' is better than the method of comparing
      solid waste management costs.

PMID- 11525473
TI  - Stormwater run-off and pollutant transport related to the activities carried out
      in a modern waste management park.
AB  - Stormwater run-off from twelve different areas and roads has been characterized
      in a modern waste disposal site, where several waste management activities are
      carried out. Using nonparametric statistics, medians and confidence intervals of
      the medians, 22 stormwater quality parameters were calculated. Suspended solids,
      chemical oxygen demand, biochemical oxygen demand, total nitrogen and total
      phosphorus, as well as run-off from several areas, showed measured values above
      standard limits for discharge into recipient waters--even higher than those of
      leachate from covered landfill cells. Of the heavy metals analyzed, copper, zinc
      and nickel were the most prevalent, being detected in every sample. Higher
      concentrations of metals such as zinc, nickel, cobalt, iron and cadmium were
      found in run-off from composting areas, compared to areas containing stored and
      exposed scrap metal. This suggests that factors other than the total amount of
      exposed material affect the concentration of metals in run-off, such as binding
      to organic compounds and hydrological transport efficiency. The pollutants
      transported by stormwater represent a significant environmental threat,
      comparable to leachate. Careful design, monitoring and maintenance of stormwater
      run-off drainage systems and infiltration elements are needed if infiltration is
      to be used as an on-site treatment strategy.

PMID- 11525474
TI  - Permeability of lime-activated pulverised fuel ash to metal-containing permeants.
AB  - Lime-activated pulverised fuel ash (PFA) has been leach tested under a range of
      pH conditions and the permeability of compacted samples determined using
      distilled water and aqueous solutions of Ca2+, Zn2+, Cd2+ and Mg2+. Although
      permeabilities were relatively high when tested with distilled water (> 1x10(-7)
      m/s), permeation with 0.05M metal solutions resulted in rapid reductions in
      permeability to less than 1x10(-10) m/s. Leachate and permeant solution analysis
      shows that metal ion release from samples is low. The reduction in permeability
      is believed to be due to pore sealing resulting primarily from metal hydroxide
      precipitation and results in a metal concentration gradient across the sample
      thickness. Lime-activated PFA therefore acts as both a chemical and physical
      barrier to metal ion migration and has the potential to form low permeability
      barriers.

PMID- 11525475
TI  - Purification of metal finishing waste waters with zeolites and activated carbons.
AB  - Sixteen zeolites and 5 activated carbons were tested for the removal of nickel,
      zinc, cadmium, copper, chromium, and cobalt from waste simulants mimicking
      effluents produced in metal plating plants. The best performances were obtained
      from 4 zeolites: A, X, L, and ferrierite types and from 2 carbon types made from
      lignite and peat. The distribution coefficients for these sorbents were in the
      range of 10,000-440,000 ml/g. Column experiments showed that the most effective
      zeolites for Zn, Ni, Cu, and Cd were A and X type zeolites. The activated
      carbons, Hydrodarco 3000 and Norit Row Supra, exhibited good sorption properties
      for metals in aqueous solutions containing complexing agents.

PMID- 11525476
TI  - The role of aerobic activity on refuse temperature rise: II. Experimental and
      numerical modelling.
AB  - The biodegradation of a model waste is studied in a 300-litre pilot. The aim is
      to better understand the role of biochemical processes on the temperature rise,
      in relation to landfill management protocols. The variations of temperature and
      gas composition distributions in the waste are accurately measured and analysed.
      The observations confirm that biological consumption of the oxygen diffusing
      through the waste is the main source of heat. A theoretical modelling of coupled
      heat and oxygen transfers in fresh refuse is then proposed. Numerical results are
      in good agreement with experimental data, but it appears that biochemical
      kinetics should account for the carbon availability limitation. Finally, a
      prediction of the temperature field in a landfill is presented.

PMID- 11525477
TI  - Attenuation of landfill leachate by clay liner materials in laboratory columns:
      2. Behaviour of inorganic contaminants.
AB  - The chemical attenuation of inorganic contaminants in methanogenic landfill
      leachate, spiked with heavy metals (Cd, Cd, Ni and Zn), by two UK clay liner
      materials was compared in laboratory columns over 15 months. Ammonium was
      attenuated by ion-exchange but this attenuation was finite and when exhausted,
      NH4 passed through the liners at concentrations found in the leachate. The
      breakthrough behaviour of NH4 could be described by a simple distribution
      coefficient. Heavy metals were attenuated by sorption and precipitation of metal
      sulphide and carbonate compounds near the top of the liner. Adequate SO4 and
      CaCO3 in the liner is necessary to ensure the long term retention of heavy
      metals, and pH buffering agents added to stabilise reactive metal fractions
      should be admixed with the liner. Some metals may not be chemically attenuated by
      clay liners due to the formation of stable complexes with organic and/or
      colloidal fractions in leachate. Flushing of the liners with oxygenated water
      after leachate caused mobilisation of attenuated contaminants. Sorbed NH4 was
      released by the liners but groundwater loadings were manageable. Re-oxidation of
      metal sulphides under these conditions resulted in the release of heavy metals
      from the liners when the pH buffering capacity was poor. Contaminant attenuation
      by the clay liners was similar and the attenuation of NH4 and heavy metals could
      be predicted from the geochemical properties of the liner using simple tests. A
      conceptual model of clay liner performance is presented. Chemical attenuation of
      inorganic pollutants can be included in containment liner design to produce a
      dual reactive-passive barrier for landfills.

PMID- 11525478
TI  - Report: landfill alternative daily cover: conserving air space and reducing
      landfill operating cost.
AB  - Title 40, Part 258 of the Code of Federal Regulations, Solid Waste Disposal
      Facility Criteria, commonly referred to as Subtitle D, became effective on
      October 9, 1993. It establishes minimum criteria for solid waste disposal
      facility siting, design, operations, groundwater monitoring and corrective
      action, and closure and postclosure maintenance, while providing EPA-approved
      state solid waste regulatory programs flexibility in implementing the criteria.
      Section 258.21(a) [40 CFR 258.21(a)] requires owners or operators of municipal
      solid waste landfill (MSWLF) units to cover disposed solid waste with 30cm of
      earthen material at the end of the operating day, or at more frequent intervals,
      if necessary, to control disease vectors, fires, odours, blowing litter, and
      scavenging. This requirement is consistent with already existing solid waste
      facility regulations in many states. For many MSWLFs, applying daily cover
      requires the importation of soil which increases landfill operating costs. Daily
      cover also uses valuable landfill air space, reducing potential operating revenue
      and the landfill's operating life. 40 CFR 258.21 (b) allows the director of an
      approved state to approve alternative materials of an alternative thickness if
      the owner or operator demonstrates that the alternative material and thickness
      will control disease vectors, fires, odours, blowing litter, and scavenging
      without presenting a threat to human health and the environment. Many different
      types of alternative daily cover (ADC) are currently being used, including
      geosynthetic tarps, foams, garden waste, and auto shredder fluff. These materials
      use less air space than soil and can reduce operating costs. This paper discusses
      the variety of ADCs currently being used around the country and their
      applicability to different climates and operating conditions, highlighting the
      more unusual types of ADC, the types of demonstrations necessary to obtain
      approval of ADC, and the impact on landfill air space and operating costs of ADC
      use.

PMID- 11525479
TI  - Identity and similarity in repetition blindness: no cross-over interaction.
AB  - The difficulty in reporting both occurrences of a repeated item is a phenomenon
      referred to as repetition blindness (RB). RB has been proposed to result from
      temporal limitations in creating separate episodic tokens for a twice-activated
      type. Recently, Chialant and Caramazza (Cognition 63 (1997) 79-119) disputed the
      conventional view that RB for non-identical words (orthographic RB, as in lice
      and lick) results from the same mechanism as identity RB, and proposed that
      orthographic RB arises from competition for lexical selection. Supporting
      evidence was that identical and merely similar words showed different amounts of
      RB as a function of stimulus onset asynchrony (lag). Four experiments failed to
      replicate Chialant and Caramazza's finding that identity RB decreases, but
      orthographic RB increases, as a function of lag. Instead, RB for all stimuli,
      including homonym pairs, declined monotonically with lag. These results are
      consistent with a common mechanism underlying RB for identical and
      orthographically similar words and with prior research suggesting that RB in
      similar words occurs at a sublexical level.

PMID- 11525480
TI  - Linguistic theory and psychological reality: a reply to Boudelaa & Marslen
      Wilson.

PMID- 11525481
TI  - Imagining physically impossible self-rotations: geometry is more important than
      gravity.
AB  - Previous studies found that it is easier for observers to spatially update
      displays during imagined self-rotation versus array rotation. The present study
      examined whether either the physics of gravity or the geometric relationship
      between the viewer and array guided this self-rotation advantage. Experiments 1-3
      preserved a real or imagined orthogonal relationship between the viewer and the
      array, requiring a rotation in the observer's transverse plane. Despite imagined
      self-rotations that defied gravity, a viewer advantage remained. Without this
      orthogonal relationship (Experiment 4), the viewer advantage was lost. We suggest
      that efficient transformation of the egocentric reference frame relies on the
      representation of body-environment relations that allow rotation around the
      observer's principal axis. This efficiency persists across different and
      conflicting physical and imagined postures.

PMID- 11525482
TI  - Morphological units in the Arabic mental lexicon.
AB  - Standard views of morphology in Modern Standard Arabic hold that surface word
      forms comprise at least two morphemes: a three-consonantal root conveying
      semantic meaning and a word pattern carrying syntactic information. An
      alternative account claims that semantic information is carried by a bi
      consonantal morphological unit called the etymon. Accordingly, in the form
      [batara] the core meaning is carried not by the tri-consonantal root morpheme
      [btr] but by the etymon morpheme [b,t] which surfaces in other forms like [batta]
      "sever", [batala] "cut off" with the same meaning "cutting". Previous
      experimental research in Semitic languages has assumed the tri-consonantal
      root/word pattern approach. In cross-modal and masked priming experiments we ask
      whether the etymon, as a more fine-grained two-consonantal morphological unit,
      can yield the morphological priming effects typically obtained with tri
      consonantal root morphemes. The results clearly show that two words sharing an
      etymon do facilitate each other both in cross-modal and masked priming even
      though they do not share a root, controlling for semantic and for form overlap
      effects. The bearing of these results on theories of morphological processing and
      representation is discussed.

PMID- 11525483
TI  - Content-blind norms, no norms, or good norms? A reply to Vranas.
AB  - In the psychology of thinking, little thought is given to what constitutes good
      thinking. Instead, normative solutions to problems have been accepted at face
      value, thereby determining what counts as a reasoning fallacy. I applaud Vranas
      (Cognition 76 (2000) 179) for thinking seriously about norms. I do, however,
      disagree with his attempt to provide post hoc justifications for supposed
      reasoning fallacies in terms of 'content-neutral' norms. Norms need to be
      constructed for a specific situation, not imposed upon it in a content-blind way.
      The reason is that content-blind norms disregard relevant structural properties
      of the given situation, including polysemy, reference classes, and sampling. I
      also show that content-blind norms can, unwittingly, lead to double standards:
      the norm in one problem is the fallacy in the next. The alternative to content
      blind norms is not no norms, but rather carefully designed norms.

PMID- 11525484
TI  - Prior knowledge on the illumination position.
AB  - Visual perception is fundamentally ambiguous because an infinite number of three
      dimensional scenes are consistent with our retinal images. To circumvent these
      ambiguities, the visual system uses prior knowledge such as the assumption that
      light is coming from above our head. The use of such assumptions is rational when
      these assumptions are related to statistical regularities of our environment. In
      confirmation of previous visual search experiments, we demonstrate here that the
      assumption on the illumination position is in fact biased to the above-left
      rather than directly above. This bias to the left reaches 26 degrees on average
      in a more direct shape discrimination task. Both right-handed and left-handed
      observers have a similar leftward bias. We discuss the possible origins of this
      singular bias on the illumination position.

PMID- 11525485
TI  - The effect of harmonic context on phoneme monitoring in vocal music.
AB  - The processing of a target chord depends on the previous musical context in which
      it has appeared. This harmonic priming effect occurs for fine syntactic-like
      changes in context and is observed irrespective of the extent of participants'
      musical expertise (Bigand & Pineau, Perception and Psychophysics, 59 (1997)
      1098). The present study investigates how the harmonic context influences the
      processing of phonemes in vocal music. Eight-chord sequences were presented to
      participants. The four notes of each chord were played with synthetic phonemes
      and participants were required to quickly decide whether the last chord (the
      target) was sung on a syllable containing the phoneme /i/ or /u/. The musical
      relationship of the target chord to the previous context was manipulated so that
      the target chord acted as a referential tonic chord or as a congruent but less
      structurally important subdominant chord. Phoneme monitoring was faster for the
      tonic chord than for the subdominant chord. This finding has several implications
      for music cognition and speech perception. It also suggests that musical and
      phonemic processing interact at some stage of processing.

PMID- 11525486
TI  - Sorption of the neutral and charged forms of pentachlorophenol on soil: evidence
      for different mechanisms.
AB  - Laboratory soil sorption experiments have been conducted on pentachlorophenol
      (PCP) at different pH values in an attempt to elucidate differences in sorption
      mechanisms between the charged and neutral species. Sorption of PCP on soil was
      investigated by maintaining pH 4 or 8 in batch sorption experiments. Pre
      equilibration of the soil was necessary to maintain a constant pH over the course
      of the experiments. Additionally, a CaCO3-CO2/N2 buffered solution was necessary
      to maintain a pH of 8. Sorption of the neutral PCP species conformed to a linear
      isotherm model, while a Langmuir model provided the best fit for the charged
      species. Desorption of the neutral form was completely reversible over the
      sorption times studied but the charged species exhibited some resistance to
      desorption. Temperature effects on the distribution coefficients (Kd) were
      investigated and thermodynamic parameters were calculated. The ionized species
      showed a clear decrease in Kd with increasing temperature while the protonated
      species showed no apparent trend. Enthalpies (deltaHo), entropies (deltaSo), and
      free energies (deltaGo), support the conclusions that the neutral form of PCP
      partitions by hydrophobically binding to the soil while the charged form sorbs by
      a more specific exothermic adsorption reaction.

PMID- 11525487
TI  - Inhibition of aerobic growth and nitrification of bacteria in sewage sludge by
      antibacterial agents.
AB  - Toxicity of antibacterial agents on environmentally relevant bacteria was
      investigated using activated sludge. The growth and nitrifying inhibiting effects
      for activated sludge of benzyl penicillin (penicillin G) (BP), tetracycline (TC),
      chlortetracycline (CTC), oxytetracycline (OTC), olaquindox (O), streptomycin
      (ST), tiamulin (TI), tylosin (TYL) sulfadiazine (SDZ), metronidazole (MET), and
      oxolinic acid (OXA) was investigated. Studies were performed in accordance to the
      ISO 15522 (1999) and ISO 9509 (1989) test guidelines, respectively. The toxicity
      (EC50 value, mg/L) found with the ISO 15522 was in decreasing EC50 values; O
      (95.7), BP (84.6), TYL (54.7), TI (14.3), TC (2.2), OTC (1.2), ST (0.47), CTC
      (0.40), and OXA (0.1). No observed effect concentrations (NOECs) (mg/L) of 100
      and 60, respectively was found for MET and SDZ. Triplicate tests assessing the
      effects of the antibacterial agents on the nitrification rate gave indications
      only as the level of increased or decreased rate. More accurate data for the
      inhibition of Nitrosomonas europaea was found with a suspended culture of the
      nitrifying bacteria. The toxicity (EC50 value, mg/L) found was in decreasing EC50
      values; TI (23.3), SDZ (17.0), TC (4.0), OTC (1.7), OXA (1.0), CTC (0.64), O
      (0.03), ST (0.02). For MET and TYL, NOECs (mg/L) of 100 and 50 were found,
      respectively. The antibacterial agents were also assessed using a pour plate
      method with both (separately tested) activated sludge bacteria and N. europeae
      showing to be 5 to 10 times more potent to most agents except SDZ, TI, and MET.

PMID- 11525488
TI  - Evaluation of contamination, by different elements, in terrestrial mosses.
AB  - Evaluation was made of the degree to which samples of terrestrial mosses
      (Scleropodium purum and Hypnum cupressiforme) collected in Galicia (NW Spain)
      were contaminated by different elements. The concentrations of Al, As, Ca, Cd,
      Co, Cr, Cu, Fe, Hg, K, Mg, Mn, Na, Ni, Pb, S, Se, and Zn in the mosses were
      determined, then the contamination factors were calculated by dividing each value
      by the corresponding background level of that element. To assess contamination
      using contamination factors (CFs), a scale was established that allowed
      categorization of sampling sites for each element determined. The proposed scale
      comprises six categories, ranging from CF values of less than 1 (no
      contamination) to values of greater than 27 (extreme contamination). Finally, all
      available information was brought together and summarized in a contamination
      index. This index has the advantage that it takes into account the toxicity of
      the elements and that can be used with an already existing scale of
      classification.

PMID- 11525489
TI  - Development of an improved rapid enzyme inhibition bioassay with marine and
      freshwater microalgae using flow cytometry.
AB  - A rapid toxicity test based on inhibition of esterase activity in marine and
      freshwater microalgae (Selenastrum capricornutum, Chlorella sp., Dunaliella
      tertiolecta, Phaeodactylum tricornutum, Tetraselmis sp., Entomoneis cf.
      punctulata, Nitzschia cf. paleacea) was developed using flow cytometry. Uptake of
      fluorescein diacetate (FDA) was optimized for each species by varying the
      substrate concentration, incubation time, and media pH. Propidium iodide (PI) was
      utilized to assess membrane integrity. The optimized FDA/PI staining procedure
      was then used to assess the toxicity of copper in short-term exposures (1-24 h).
      Esterase activity was a sensitive indicator of copper toxicity in S.
      capricornutum and E. cf. punctulata. As copper concentrations increased, esterase
      activity decreased in a concentration-dependent manner. The 3- and 24-h EC50
      values (based on mean activity states) were 112 microg Cu L(-1) (95% confidence
      limits 88-143) and 51 microg Cu L(-1) (95% confidence limits 38-70) for S.
      capricornutum and 47 microg Cu L(-1) (95% confidence limits 43-51) and 9.1 microg
      Cu L(-1) (95% confidence limits 7.6-11) for E. cf. punctulata, respectively. This
      enzyme inhibition endpoint showed similar sensitivity to chronic growth rate
      inhibition in E. cf. punctulata (48-h and 72-h EC50 values of 17 and 18 microg L(
      1), respectively) but was less sensitive compared to growth for S. capricornutum
      (48-h and 72-h EC50 values of 4.9 and 7.5 microg L(-1), respectively). For the
      other five species tested, inhibition of FDA fluorescence was relatively
      insensitive to copper, even at copper concentrations that severely inhibited cell
      division rate. These short-term bioassays that detect sublethal endpoints may
      provide a more rapid and cost-effective way of monitoring contaminant impacts in
      natural waters.

PMID- 11525490
TI  - Acute and chronic effects of particle-associated fenvalerate on stream
      macroinvertebrates: a runoff simulation study using outdoor microcosms.
AB  - Agricultural edge-of-field runoff usually contaminates surface waters with
      particle-associated pesticides. However, the acute and chronic effects on the
      aquatic macroinvertebrate communities have rarely been addressed. Outdoor flow
      through stream microcosms were exposed for 1 h in triplicate to approximately 3.1
      g/L of total suspended solids spiked with 0.0, 13.6, 136, or 1,365 microg/kg of
      the pyrethroid insecticide fenvalerate (FV). The effects on eight species typical
      of agricultural streams were monitored for 93 days. Gammarus pulex (Amphipoda)
      and Hydropsyche angustipennis (Trichoptera) showed a sensitive acute drift
      reaction with increased drift levels in all FV treatments (p < 0.05). The
      caddisfly species Anabolia nervosa, Plectrocnemia conspersa, and Limnephilus
      lunatus as well as the dipteran species Tipula maxima were less sensitive, with a
      significant increase in drift in the 136- and 1,365-microg/kg treatments.
      Temporal pattern of emergence was significantly altered in the 1,365-microg/kg
      treatment for A. nervosa (p < 0.05). The most sensitive species in terms of total
      emergence or survival were L. lunatus, which showed a significant effect in the
      136- and 1,365-microg/kg treatment, as well as adult and juvenile G. pulex and T.
      maxima, with a significant effect level in the 1,365-microg/kg treatment (p <
      0.05). Total emergence or survival of A. nervosa, P. conspersa, and H.
      angustipennis decreased with increasing exposure level, but differences from the
      control were not significant. Neither acute drift nor chronic mortality was
      observed for Helodes minuta (Coleoptera) and Radix peregra (Gastropoda). This
      study highlights the ecotoxicological importance and bioavailability of field
      relevant levels of particle-associated hydrophobic chemicals transiently
      introduced into surface waters during runoff events.

PMID- 11525491
TI  - A 48-h larval development toxicity test using the marine polychaete Galeolaria
      caespitosa Lamarck (Fam. Serpulidae).
AB  - Assessing the risk of effluents and other anthropogenic inputs to the receiving
      environment is ultimately best done on a site-specific basis, which often
      requires toxicity tests using organisms relevant to that environment.
      Additionally, the test species or life stage needs to be available for a
      reasonable portion of the year to allow temporal fluctuations to be assessed. A
      48-h larval development toxicity test using the marine polychaete Galeolaria
      caespitosa was developed. This test was developed as G. caespitosa releases
      viable gametes year-round, and the test species is environmentally relevant to
      the marine system receiving the liquid effluent being evaluated. Toxicity tests
      were conducted using G. caespitosa from different locations and evaluating the
      gamete response to copper. All population responses were comparable, with EC50
      values ranging from 16 to 40 microg/L copper (as CuCl2, x 2H2O). Toxicity tests
      were also conducted using G. caespitosa gametes with an effluent produced by a
      lead smelting operation. The response of the G. caespitosa test with this
      effluent was compared with three other test methods using two microalgal species,
      Isochrysis sp. and Nitzschia closterium, and gametes from the mussel Mytilus
      edulis. The G. caespitosa larval development toxicity test was the most sensitive
      test to the effluent, with EC50 values ranging from 1-23% effluent, while it
      ranked second in sensitivity to copper. This test could be applied to other
      common serpulids worldwide.

PMID- 11525492
TI  - The influence of suspended particles on the acute toxicity of 2-chloro-4-nitro
      aniline, cadmium, and pentachlorophenol on the valve movement response of the
      zebra mussel (Dreissena polymorpha).
AB  - The Dreissena-Monitor is a biological early warning system for the continuous
      monitoring of river water quality, based on the valve movements of two groups of
      42 zebra mussels (Dreissena polymorpha). Laboratory experiments with Cd, PCP, and
      2-chloro-4-nitro-aniline were conducted in combination with suspended particles
      (a mixture of stinging nettle powder, bentonite, and quartz powder). An increase
      of suspended particles up to a nominal concentration of 540 mg/L within 5 min did
      not evoke any reactions by the mussels significantly different from normal. The
      distribution between water and solids was analyzed for Cd and 2-chloro-4
      nitroaniline, with the result that the former quickly adsorbed to the particles,
      whereas the latter did not bind to the particles at all. The behavior of the
      zebra mussels revealed that the detection of 2-chloro-4-nitro-aniline was not
      affected by the presence of suspended matter. In the cases of Cd and PCP, D.
      polymorpha was able to detect these substances when they were particle-associated
      at least as well or better as when they were dissolved in the water. The results
      are discussed with respect to the physiology of the organisms and the
      bioavailability of toxicants, as well as to the consequences these results may
      have under field conditions.

PMID- 11525493
TI  - Survival and molting of the pea crab larvae Tunicotheres moseri Rathbun 1918
      (Brachyura, Pinnotheridae) exposed to copper.
AB  - The acute lethal toxicity of copper, as well as its sublethal effect on molting,
      was studied on larval and postlarval stages of the pinnotherid crab Tunicotheres
      moseri. The most sensitive stage was zoea I, presenting a significant mortality
      above 0.5 microg x L(-1). Abnormal setation of the maxillipeds was observed in
      zoeae II moulted from zoeae I exposed to 100 microg x L(-1) and higher copper
      concentrations, causing a reduced swimming activity of the larvae. This pathology
      could be reverted after molting of affected zoea II to megalopa, which would be
      the first report in crustacean larvae that states the possibility of reverting
      morphological abnormalities after molting. For zoeae II and megalopae, the
      inhibition of molting and high mortality was registered at 1,000 microg x L(-1).
      The effect of copper on the duration of the larval and postlarval stages was
      differential: It retarded the duration of the stage zoea I, did not modify that
      of zoea II, and accelerated the ecdysis of the megalopae to first crab. However,
      precocious molting to megalopae was associated with a smaller body size at the
      concentration of 100 microg x L(-1). This differential effect of copper on the
      larval stages throughout the larval development could be ecologically relevant.
      Because of their lecithotrophia, their short developmental period, their good
      survival in control conditions, and the high sensitivity showed to copper
      (especially zoea I), larvae of T. moseri have shown that they are an excellent
      model for studying the effect of pollutant on survival, molting rate, growth, and
      morphogenetic changes during development.

PMID- 11525494
TI  - Stored retinoids in populations of the estuarine fish Fundulus heteroclitus
      indigenous to PCB-contaminated and reference sites.
AB  - Concentrations of retinoids, derivatives of vitamin A, were measured in
      populations of the nonmigratory estuarine fish Fundulus heteroclitus, indigenous
      to a reference site and a site highly contaminated with polychlorinated biphenyls
      (PCBs) to address the hypothesis that contaminant exposure causes depletion of
      stored retinoids in native fish populations. To assess differences related to
      chemical exposure, as well as season and diet, hepatic retinoid analyses were
      conducted using fish collected early and late in the natural spawning season and
      after laboratory holding. Though hepatic retinoid composition was generally
      similar among groups, hepatic retinoid concentrations differed. Laboratory-held
      fish had higher hepatic retinyl ester concentrations than field-collected fish.
      Among field-collected fish, those collected early in the spawning season had
      higher hepatic retinyl ester concentrations than those collected later in the
      spawning season. Although there was no evidence of the dramatic retinoid
      depletions that have been reported in highly exposed populations of other fish
      species, hepatic retinoid stores were consistently lower in F. heteroclitus
      indigenous to the highly PCB-contaminated site. These results are consistent with
      prior findings that fish from this contaminated site are relatively insensitive
      to some of the toxic effects of PCB exposures, including retinoid depletion.

PMID- 11525495
TI  - Bioaccumulation of selected PCBs in zebrafish, three-spined stickleback, and
      arctic char after three different routes of exposure.
AB  - The uptake and elimination of 20 structurally diverse tetra- to heptachlorinated
      biphenyls were studied in zebrafish (Danio rerio), three-spined stickleback
      (Gasterosteus aculeatus), and Arctic char (Salvelinus alpinus). The
      polychlorinated biphenyls (PCBs) were administered to the fish through food,
      intraperitoneal injection of peanut oil, or intraperitoneal implantation of
      silicone capsules. The retention of the PCBs in fish exposed through their diet
      was related with the substitution patterns of the compounds. Ortho-substituted
      congeners with no unsubstituted meta-para positions had high biomagnification
      potential. PCBs with low biomagnification all had adjacent vicinal hydrogens,
      indicating that congeners with this feature may have been metabolically
      eliminated. The retention characteristics of the PCBs in the diet-exposed and the
      injected zebrafish were similar. The pattern of congeners in Arctic char
      indicates that they have a lower capacity to metabolize PCBs compared to three
      spined sticklebacks and zebrafish. The levels in the fish exposed to the PCBs
      through a silastic implant were negatively correlated with the hydrophobicity of
      the congeners. Most probably congener-specific release rates of the PCBs from the
      implants mask their retention characteristics. It is suggested that food,
      mimicking the natural intake route, should be used in PCB exposure studies to
      validate extrapolations to natural situations.

PMID- 11525496
TI  - Accumulation and selective maternal transfer of contaminants in the turtle
      Trachemys scripta associated with coal ash deposition.
AB  - Coal combustion wastes are enriched in a number of potentially toxic compounds
      and may pose risks to biota exposed to the wastes. Slider turtles (Trachemys
      scripta) are common inhabitants of coal ash settling basins in South Carolina,
      USA, where they feed on contaminated prey items and accumulate high levels of
      potentially toxic compounds in their tissues. Furthermore, female sliders
      sometimes nest in contaminated spill piles and thus may expose embryos to
      contaminated soils. We examined two potential pathways by which female T. scripta
      may influence the survivorship and quality of their offspring in a contaminated
      habitat: (1) nesting in contaminated soil and (2) maternal transfer of
      pollutants. Eggs were collected from turtles captured in coal ash-polluted or
      unpolluted sites; individual clutches were incubated in both ash-contaminated and
      uncontaminated soil in outdoor, artificial nests. Incubation in contaminated soil
      was associated with reduced embryo survivorship. Adult females from the polluted
      site accumulated high levels of As, Cd, Cr, and Se in their tissues, yet Se was
      the only element transferred maternally to hatchlings at relatively high levels.
      Hatchlings from polluted-site females exhibited reduced O2 consumption rates
      compared to hatchlings from reference sites. Relatively high levels of Se
      transferred to hatchlings by females at the ash-polluted site might contribute to
      the observed differences in hatchling physiology.

PMID- 11525497
TI  - DDT and the decline of free-tailed bats (Tadarida brasiliensis) at Carlsbad
      Cavern, New Mexico.
AB  - DDT is believed to have caused the population of Brazilian free-tailed bats
      (Tadarida brasiliensis mexicana) at Carlsbad Cavern to decline severely after
      1936. Nevertheless, previous data supporting this hypothesis are limited to a
      single study from 1974, which indicated that 20% of young free-tails from the
      cavern may have died of DDE poisoning during their first southward migration. In
      this study I compared organochlorine residues among samples of free-tails
      collected in Carlsbad Cavern in 1930, 1956, 1965, 1973, and 1988. Samples of skin
      cut from dry museum specimens were chemically analyzed, except for the 1973 data,
      which were derived from analyses of whole bats minus gastrointestinal tracts.
      Accumulated residue levels of DDT compounds in bats from 1965 and 1956 exceeded
      those in 1973 bats by approximately 4.8 times and approximately 2.7 times,
      respectively. This suggests that lethal effects of DDT compounds were
      substantially greater in the 1950s and 1960s than in the 1970s. Residues in 1988
      bats resembled those for 1973 bats. It is concluded that DDT played a major role
      in this severe population decline. These results can be applied by management
      personnel in evaluating the present and future status of this population
      regarding persisting organochlorine insecticides as well as other agricultural
      chemicals now in use. The case of the Carlsbad colony is discussed relative to
      the general issue of other bat population declines.

PMID- 11525498
TI  - In ovo exposure to polychlorinated biphenyls: reproductive effects on second
      generation American kestrels.
AB  - The reproductive success of wild birds has been affected by exposure to multiple
      contaminants. Reproduction of captive American kestrels (Falco sparverius) was
      suppressed when adult birds were exposed to dietary polychlorinated biphenyls
      (PCBs). In this study, the reproductive effects of in ovo exposure to PCBs is
      explored, along with determining effects on reproduction in second-generation
      birds indirectly exposed to PCBs. Reproductive changes in this subsequent
      generation are examined separately in male and female birds. Captive American
      kestrels (F. sparerius) were hatched from clutches with eggs containing
      environmentally relevant levels of total PCBs (34.0 microg/g whole egg WW versus
      0 microg/g controls); parent birds had been fed PCB-spiked (Aroclor
      1248:1254:1260) food (7 mg/kg BW day(-1)) for 100 days until their eggs hatched.
      In 1999, the second-generation PCB birds were paired with unexposed kestrels
      having reproductive experience. In ovo PCB exposure suppressed egg laying
      completely in 25% of PCB females and resulted in delays in clutch initiation and
      smaller clutch sizes for PCB male and female pairs. There was no evidence in this
      study of in ovo PCB treatment effects on fertility or hatching success. The
      decline in reproductive success was also reflected in the reduced fledging
      success and higher incidence of complete brood mortality of PCB nestlings.
      Differences between in ovo-exposed PCB males and females but not between controls
      were evident in reproductive success. In ovo PCB exposure appears to have had
      greater effects on female kestrels until clutch completion, with a greater time
      lag between pairing and egg laying, reduced numbers of pairs laying eggs, and
      smaller clutches being laid. In ovo PCB exposure has greater effects later in the
      breeding season on male kestrels, which had poorer hatching and fledging success
      relative to the PCB females. Possible behavioral and physiological mechanisms
      involved in these reproductive changes are discussed.

PMID- 11525499
TI  - Comparison of heavy metal concentrations in tissues of red foxes from adjacent
      urban, suburban, and rural areas.
AB  - The red fox (Vulpes vulpes) is a representative of the canid family with wide
      distribution in the Northern Hemisphere and Australia. The increasing utilization
      of urbanized habitats by red foxes prompted us to test whether this species may
      be used to monitor the presence of anthropogenic pollutants in cities or suburbs.
      For that purpose, we compared the concentrations of heavy metals (Cd, Pb, Cu, Zn)
      in foxes from urban, suburban, and rural areas within the municipality of Zurich
      (Switzerland). The kidney and liver of suburban and rural foxes contained the
      highest Cd concentrations, whereas urban foxes contained the highest Pb levels.
      In the kidney of suburban foxes, Cd concentrations increased from a median value
      of 0.73 mg/kg in juvenile animals to 1.82 mg/kg in adults. Similarly, the liver
      of suburban foxes contained increasing Cd levels from a median of 0.21 mg/kg in
      juvenile animals to 0.94 mg/kg in adults. An age-dependent storage of Cd was also
      found in foxes from the rural surroundings, but no such accumulation occurred in
      urban foxes from the city center, where even adult animals contained very low Cd
      levels. Conversely, foxes from the urban center were characterized by elevated Pb
      concentrations during the first 2 years of life, but this transient Pb
      accumulation was absent in suburban or rural animals. The liver of juvenile foxes
      contained a median Pb concentration of 0.99 mg/kg in the city compared to only
      0.47 and 0.37 mg/kg in the suburban and rural area, respectively. Thus, we found
      that animals from separate environmental compartments contain different patterns
      of tissue residues, implying that red foxes may serve as a bioindicator species
      to detect certain toxic hazards in urbanized habitats.

PMID- 11525500
TI  - Organochlorine pesticides in water, sediment, crops, and human fluids in a
      farming community in Ghana.
AB  - A total of 208 samples of water, sediment, tomato crops, blood, and mothers'
      breast milk were collected from the environs of Akumadan, a prominent vegetable
      farming community in Ghana. The samples were analyzed for organochlorine (OC)
      pesticide residues. Lindane and endosulfan were found in water and sediment,
      while other OC pesticide residues, such as hexachlorobenzene (HCB), p,p'-DDE, and
      heptachlor epoxide, were additionally found in sediment. Heptachlor epoxide was
      the only OC residue detected in appreciable quantity in crops. Significantly
      higher HCB and p,p'-DDE residues were found in blood and milk samples. The mean
      values of HCB and p,p'-DDE in blood were 30 microg/kg and 380 microg/kg,
      respectively. The mean values of HCB and p,p'-DDE in milk were 40 microg/kg fat
      (1.75 microg/kg whole milk) and 490 microg/kg fat (17.15 microg/kg whole milk),
      respectively. The presence of OC pesticide residues in breast milk requires
      further monitoring and epidemiological studies to clarify possible detrimental
      health effects in breast-fed infants.

PMID- 11525501
TI  - Polybrominated diphenyl ethers in Swedish human liver and adipose tissue.
AB  - Paired samples of human liver and adipose tissue were analyzed for polybrominated
      diphenyl ethers (PBDEs) containing 3-6 bromine atoms. The samples were obtained
      at autopsy from one woman and four men at the age of 47 and 66-83 years,
      respectively. PBDEs were found in all samples. The sum of nine PBDE congeners
      ranged 5-18 ng/g lipids and 4-8 ng/g lipids in liver and adipose tissue,
      respectively. In three paired samples the concentrations were similar in liver
      and adipose tissue, while in two of the pairs the concentrations were higher in
      liver than in adipose tissue. The PBDE congeners 2,2',4,4'-tetraBDE (BDE-47),
      2,2',4,4',5-pentaBDE (BDE-99), and 2,2',4,4',5,5'-hexaBDE (BDE-153) occurred at
      highest levels and constituted together 87-96% and 84-94% of the total sum of
      PBDEs in liver and adipose tissue, respectively. The levels of PBDEs were
      compared to those of polychlorinated biphenyls (PCBs), polychlorinated
      naphthalenes (PCNs), 1,1-bis(4-chlorophenyl)-2,2-dichloroethene (p,p'-DDE), and
      hexachlorobenzene (HCB).

PMID- 11525502
TI  - Continuous surveillance of organochlorine compounds in human breast milk from
      1972 to 1998 in Osaka, Japan.
AB  - The presence of chlorinated organic compounds in breast milk of lactating women
      living in Osaka Prefecture, Japan, has been followed since 1972. Following the
      highest concentration found at the start of the measurements, contamination by
      polychlorinated biphenyls (PCBs) and organochlorine pesticides, such as beta-HCH
      and DDT declined to about 3-13% of the peak levels by the mid-1970s and continued
      to decrease to low-level equilibrium states. This decline varies greatly with the
      chemical compound. In comparison with 1970s, when the contamination of breast
      milk was highest, the beta-HCH level fell to about 3%, DDT to about 7%, and PCBs
      to about 13%, representative of different half-lives in the environment and the
      particular persistence of PCB. In the case of chlordane, a termite insecticide,
      more than 10 years have passed since its use was prohibited in Japan, but it
      continues to be found in human breast milk, although at a low level.

PMID- 11525503
TI  - Urinary bromide levels probably dependent to intake of foods such as sea algae.
AB  - The purpose of the present study is to examine if the bromide (Br) level in urine
      (Br-U) varies substantially among adult general populations of either sex or of
      different dietary habits. For this purpose, morning spot urine samples (about 50
      per group) were collected from six groups of people, i.e., one group each of men
      and women in a city in Japan (thus two groups in Japan) and one group each of
      women in two urban and two rural areas in central and northeast China (four
      groups in China). The samples were analyzed for Br by ECD-gas chromatography
      after derivatization to methyl bromide. Br-U essentially followed a normal
      distribution. Whereas there was only a marginal difference in Br-U between men
      (7.7 +/- 2.5 mg/L as an arithmetic mean and arithmetic standard deviation) and
      women (8.1 +/- 2.9 mg/L) in Japan, and no difference between the urban (2.3 +/-
      0.8 mg/L) and rural women (2.6 +/- 1.1 mg/L) in China, the difference between
      Japanese (8.1 +/- 2.9 mg/L) and Chinese women (2.3 +/- 0.8 mg/L for two cities
      and 2.6 +/- 1.1 mg/L for two villages) was substantial. A literature survey
      suggested variation in dietary habits, especially that in sea algae intake, is a
      possible factor affecting the observed difference in Br-U between the two ethnic
      groups. Contribution of Br in cereals after fumigation with, e.g., methyl
      bromide, was also thought to be possible. The implication of difference in
      background Br-U levels is discussed in relation to biological monitoring of
      exposure to Br-containing industrial chemicals, such as 1- and 2-bromopropane.

PMID- 11525504
TI  - Molecular mechanisms of plant metal tolerance and homeostasis.
AB  - Transition metals such as copper are essential for many physiological processes
      yet can be toxic at elevated levels. Other metals (e.g. lead) are nonessential
      and potentially highly toxic. Plants--like all other organisms--possess
      homeostatic mechanisms to maintain the correct concentrations of essential metal
      ions in different cellular compartments and to minimize the damage from exposure
      to nonessential metal ions. A regulated network of metal transport, chelation,
      trafficking and sequestration activities functions to provide the uptake,
      distribution and detoxification of metal ions. Some of the components of this
      network have now been identified: a number of uptake transporters have been
      cloned as well as candidate transporters for the vacuolar sequestration of
      metals. Chelators and chaperones are known, and evidence for intracellular metal
      trafficking is emerging. This recent progress in the molecular understanding of
      plant metal homeostasis and tolerance is reviewed.

PMID- 11525505
TI  - Dynamics of callose deposition and beta-1,3-glucanase expression during
      reproductive events in sexual and apomictic Hieracium.
AB  - Callose accumulates in the walls of cells undergoing megasporogenesis during
      embryo sac formation in angiosperm ovules. Deficiencies in callose deposition
      have been observed in apomictic plants and causal linkages between altered
      callose deposition and apomictic initiation proposed. In apomictic Hieracium,
      embryo sacs initiate by sexual and apomictic processes within an ovule, but
      sexual development terminates in successful apomicts. Callose deposition and the
      events that lead to sexual termination were examined in different Hieracium
      apomicts that form initials pre- and post-meiosis. In apomictic plants, callose
      was not detected in initial cell walls and deficiencies in callose deposition
      were not observed in cells undergoing megasporogenesis. Multiple initial
      formation pre-meiosis resulted in physical distortion of cells undergoing
      megasporogenesis, persistence of callose and termination of the sexual pathway.
      In apomictic plants, callose persistence did not correlate with altered spatial
      or temporal expression of a beta-1,3-glucanase gene (HpGluc) encoding a putative
      callose-degrading enzyme. Expression analysis indicated HpGluc might function
      during ovule growth and embryo sac expansion in addition to callose dissolution
      in sexual and apomictic plants. Initial formation pre-meiosis might therefore
      limit the access of HpGluc protein to callose substrate while the expansion of
      aposporous embryo sacs is promoted. Callose deposition and dissolution during
      megasporogenesis were unaffected when initials formed post-meiosis, indicating
      other events cause sexual termination. Apomixis in Hieracium is not caused by
      changes in callose distribution but by events that lead to initial cell
      formation. The timing of initial formation can in turn influence callose
      dissolution.

PMID- 11525506
TI  - Isolation and characterisation of a full-length genomic clone encoding a
      plastidic glucose 6-phosphate dehydrogenase from Nicotiana tabacum.
AB  - We describe here the isolation and characterisation of the first full-length
      genomic clone encoding a plant glucose 6-phosphate dehydrogenase (G6PDH; EC
      1.1.1.49) from Nicotiana tabacum L. cv Samsun. The gene was expressed in all
      tissues, including roots, leaves, stems and flowers. Comparison of the gene with
      other known plant G6PDH cDNAs grouped this sequence with plastidic isoforms. The
      protein, minus a putative plastidic transit sequence, was overexpressed in
      Escherichia coli as a glutathione S-transferase fusion protein. The resulting
      protein was shown to be immunologically related to the potato plastidic G6PDH.
      This suggests that the sequence described here codes for a plastidic isoform.
      Plastidic G6PDH mRNA was induced in both roots and leaves in response to KNO3,
      and the induction in roots was approximately 4 times the response seen in leaves.
      Sequence analysis of the 5'-untranslated region of the genomic clone indicated
      the presence of several NIT2 elements, which may contribute to the control of the
      expression of this gene. Plastidic G6PDH mRNA levels did not appear to respond to
      light.

PMID- 11525507
TI  - Enzymatic characterization of the recombinant Arabidopsis thaliana nitrilase
      subfamily encoded by the NIT2/NIT1/NIT3-gene cluster.
AB  - Three of the nitrilase isoenzymes of Arabidopsis thaliana (L.) Heynh. are located
      on chromosome III in tandem and these genes (NIT2/NIT1/NIT3 in the 5'-->3'
      direction) encode highly similar polypeptides. Copy DNAs encompassing the entire
      coding sequences for all three nitrilases were expressed in Escherichia coli as
      fusion proteins containing a C-terminal hexahistidine extension. All three
      nitrilases were obtained as enzymatically active proteins, and their
      characteristics were determined, including a detailed comparative analysis of
      their substrate preferences. All three nitrilases converted indole-3-acetonitrile
      (IAN) to indole-3-acetic acid (IAA), albeit, compared to the most effective
      substrates found, phenylpropionitrile (PPN), allylcyanide,
      (phenylthio)acetonitrile and (methylthio)acetonitrile, with low affinity and
      velocity. The preferred substrates are either naturally occurring substrates,
      which may originate from glucosinolate breakdown, or they are close relatives of
      these. Thus, a major function of NIT1, NIT2 and NIT3 is assigned to be the
      conversion to carboxylic acids of nitriles from glucosinolate turnover or
      degradation. While all nitrilases exhibit a similar pH optimum around neutral,
      and NIT1 and NIT3 exhibit a similar temperature optimum around 30 degrees C
      independent of the substrate analyzed (IAN, PPN), NIT2 showed a remarkably
      different temperature optimum for IAN (15 degrees C) and PPN (35-40 degrees C). A
      potential role for NIT2 in breaking seed dormancy in A. thaliana by low
      temperatures (stratification), however, was ruled out, although NIT2 was the
      predominantly expressed nitrilase isoform in developing embryos and in
      germinating seeds, as judged from an analysis of beta-glucuronidase reporter gene
      expression under the control of the promoters of the four isogenes. It is
      possible that NIT2 is involved in supplying IAA during seed development rather
      than during stratification.

PMID- 11525508
TI  - The timing and manner of disassembly of the apparatuses for chloroplast and
      mitochondrial division in the red alga Cyanidioschyzon merolae.
AB  - The timing and manner of disassembly of the apparatuses for chloroplast division
      (the plastid-dividing ring; PD ring) and mitochondrial division (the
      mitochondrion-dividing ring; MD ring) were investigated in the red alga
      Cyanidioschyzon merolae De Luca, Taddei and Varano. To do this, we synchronized
      cells both at the final stage of and just after chloroplast and mitochondrial
      division, and observed the rings in three dimensions by transmission electron
      microscopy. The inner (beneath the stromal face of the inner envelope) and middle
      (in the inter-membrane space) PD rings disassembled completely, and disappeared
      just before completion of chloroplast division. In contrast, the outer PD and MD
      rings (on the cytoplasmic face of the outer envelope) remained in the cytosol
      between daughter organelles after chloroplast and mitochondrial division. The
      outer rings started to disassemble and disappear from their surface just after
      organelle division, initially clinging to the outer envelopes at both edges
      before detaching. The results suggest that the two rings inside the chloroplast
      disappear just before division, and that this does not interfere with completion
      of division, while the outer PD and MD rings function throughout and complete
      chloroplast and mitochondrial division. These results, together with previous
      studies of C. merolae, disclose the entire cycle of change of the PD and MD
      rings.

PMID- 11525509
TI  - pho3: a phosphorus-deficient mutant of Arabidopsis thaliana (L.) Heynh.
AB  - A novel P-deficient mutant of Arabidopsis thaliana, pho3, was isolated by
      screening for root acid phosphatase (APase) activity in plants grown under low-P
      conditions. pho3 had 30% less APase activity in roots than the wild type and, in
      contrast to wild-type plants, root APase activity did not increase in response to
      growth in low P. However, shoot APase activity was higher in pho3 than in the
      wild-type plants. In addition, the pho3 mutant had a P-deficient phenotype, even
      when grown in P-sufficient conditions. The total P content of 11-d-old pho3
      plants, grown in agar media with a plentiful supply of P, was about 25% lower
      than the wild-type level in the shoot, and about 65% lower in the roots. In the
      rosette leaves of mature soil-grown pho3 plants the total P content was again
      reduced, to about 50% of wild-type levels. pho3 exhibited a number of
      characteristics normally associated with low-P stress, including severely reduced
      growth, increased anthocyanin content (at least 100-fold greater than the wild
      type in soil-grown plants) and starch accumulation. The results suggest that the
      mutant is unable to respond to low internal P levels, and may lack a transporter
      or a signalling component involved in regulating P nutrition.

PMID- 11525510
TI  - Characterisation and high-resolution distribution of a matrix attachment region
      binding protein (MFP1) in proliferating cells of onion.
AB  - The first matrix attachment region (MAR)-binding protein sequenced in plants,
      MFP1, has been characterised in two dicot species. Based on their antigenic
      relationship, we report here the conservation of MFP1-like proteins in
      proliferating root cells of onion (Allium cepa L). Two MFP1-like proteins with
      different molecular masses and solubilities were detected. The most abundant was
      a 90-kDa basic protein, presenting several separate spots in two-dimensional
      blots. The MFP1 was partially soluble and, similar to the proliferating cell
      nuclear antigen (PCNA)-labelled replication factories in the nucleus and nuclear
      matrix, was localised at discrete foci as detected by confocal microscopy. High
      resolution immunolocalisation of MFP1 by electron microscopy identified the foci
      as nuclear structures, some of them containing PCNA, which are ultrastructurally
      similar to the replication factories described in animal cells. Our data provide
      the first report on MFP1-like proteins in the Alliaceae. In addition, we present
      evidence of the presence of AcMFP1 in the putative replication factories.

PMID- 11525511
TI  - Plasma-membrane H+-ATPases are expressed in pitchers of the carnivorous plant
      Nepenthes alata Blanco.
AB  - Nepenthes is a unique genus of carnivorous plants that can capture insects in
      trapping organs called pitchers and digest them in pitcher fluid. The pitcher
      fluid includes digestive enzymes and is strongly acidic. We found that the fluid
      pH decreased when prey accumulates in the pitcher fluid of Nepenthes alata. The
      pH decrease may be important for prey digestion and the absorption of prey
      derived nutrients. To identify the proton pump involved in the acidification of
      pitcher fluid, plant proton-pump homologs were cloned and their expressions were
      examined. In the lower part of pitchers with natural prey, expression of one
      putative plasma-membrane (PM) H+-ATPase gene, NaPHA3, was considerably higher
      than that of the putative vacuolar H+-ATPase (subunit A) gene, NaVHA1, or the
      putative vacuolar H+-pyrophosphatase gene, NaV-HP1. Expression of one PM H+
      ATPase gene, Na-PHA1, was detected in the head cells of digestive glands in the
      lower part of pitchers, where proton extrusion may occur. Involvement of the PM
      H+-ATPase in the acidification of pitcher fluid was also supported by experiments
      with proton-pump modulators; vanadate inhibited proton extrusion from the inner
      surface of pitchers, whereas bafilomycin A1 did not, and fusicoccin induced
      proton extrusion. These results strongly suggest that the PM H+-ATPase is
      responsible for acidification of the pitcher fluid of Nepenthes.

PMID- 11525512
TI  - Expression pattern of the Arabidopsis thaliana AtEP3/AtchitIV endochitinase gene.
AB  - The carrot (Daucus carota L.) EP3 chitinase was shown to be essential for somatic
      embryo formation in a carrot mutant cell line. We identified the Arabidopsis
      thaliana (L.) Heynh. ortholog of the carrot EP3-3 chitinase gene, designated as
      AtEP3/AtchitIV and analyzed its expression in Arabidopsis by means of reverse
      transcription-polymerase chain reaction and promoter::beta-glucuronidase and
      luciferase fusions. As in carrot, the gene is expressed during somatic
      embryogenesis in "nursing" cells surrounding the embryos but not in embryos
      themselves. In plants, gene expression is found in mature pollen and growing
      pollen tubes until they enter the receptive synergid, but not in endosperm and
      integuments as in carrot. Post-embryonically, expression is found in hydathodes,
      stipules, root epidermis and emerging root hairs, indicating that the Arabidopsis
      chitinase may have a function that is not restricted to embryogenesis.

PMID- 11525513
TI  - Sterol composition and growth of transgenic tobacco plants expressing type-1 and
      type-2 sterol methyltransferases.
AB  - Transgenic tobacco (Nicotiana tabacum L.) plants with altered sterol composition
      were generated by transformation with plant cDNAs encoding type-1 and type-2
      sterol methyltransferases (SMTs; EC 2.1.1.41). For both SMT1 and SMT2
      transformants, the transformation was associated with a reduction in the level of
      cholesterol, a non-alkylated sterol. In SMT1 transformants a corresponding
      increase of alkylated sterols, mainly 24-methyl cholesterol, was observed. On the
      other hand, in SMT2 transformants the level of 24-methyl cholesterol was reduced,
      whereas the level of sitosterol was raised. No appreciable alteration of total
      sterol content was observed for either genotype. The general phenotype of
      transformants was similar to that of controls, although SMT2 transformants
      displayed a reduced height at anthesis. The results show that plant sterol
      composition can be altered by transformation with an SMT1 cDNA without adverse
      effects on growth and development, and provide evidence, in planta, that SMT1
      acts at the initial step in sterol alkylation.

PMID- 11525514
TI  - Unusual tolerance to high temperatures in a new herbicide-resistant D1 mutant
      from Glycine max (L.) Merr. cell cultures deficient in fatty acid desaturation.
AB  - The unusual tolerance to heat stress of STR7, an atrazine-resistant mutant
      isolated from photosynthetic cell-suspension cultures of soybean (Glycine max L.
      Merr. cv. Corsoy) and characterized previously [M. Alfonso et al. (1996) Plant
      Physiol 112:1499-1508] has been studied. The STR7 mutant maintained normal growth
      and fluorescence parameters at higher temperatures than the wild type (WT). The
      temperature for 50% inactivation of the oxygen-evolving activity of STR7
      thylakoids was 13 degrees C higher than in the WT. Sodium dodecyl sulfate
      polyacrylamide gel electrophoresis and immunoblot analysis with specific
      antibodies revealed that the integrity of photosystem II in the STR7 mutant was
      maintained at higher temperatures than in the WT. This unusual intrinsic
      tolerance to high temperatures contrasted with the higher sensitivity to heat
      stress reported as a feature linked to the triazine-resistance trait. The
      chloroplast membrane of STR7 accumulated an unusually high content of saturated
      C16:0 and reduced levels of C16:1 and C18:3 unsaturated fatty acids compared with
      the WT. Among all the lipid classes, chloroplastic lipids synthesized via the
      prokaryotic pathway (mono-galactosyl-diacyl-glycerol, phosphatidylglycerol and di
      galactosyl-diacyl-glycerol), which represented more than 75% of the total lipid
      classes, showed the most substantial differences in C16:0 and C18:3 levels. In
      addition, changes in the physicochemical properties of the thylakoid membrane and
      chloroplast ultrastructure were also detected.

PMID- 11525515
TI  - Characteristics of non-specific permeability and H+-ATPase inhibition induced in
      the plasma membrane of Nitella flexilis by excessive Cu2+.
AB  - Effects of Cu2+ on a non-specific conductance and H+-ATPase activity in the
      plasma membrane of the freshwater alga Nitella flexilis L. Agardh was studied
      using a conventional microelectrode voltage-clamp technique. We show that a Cu2+
      induced increase in the non-specific conductance is related to the formation of
      pores in the plasma membrane. Pore formation is the result of unidentified
      chemical reactions, since the Q10 for the rate of increase of conductance over
      time was about 3. Various oxidants and antioxidants (10 mmol/l H2O2, 10 mmol/l
      ascorbate, 100 microg/ml superoxide dismutase, and 100 microg/ml catalase) did
      not alter Cu2+-induced changes in the plasma membrane conductance, suggesting
      that the effect of Cu2+ was unrelated to peroxidation of plasma-membrane lipids.
      In contrast, organic and inorganic Ca2+-channel antagonists (nifedipine, Zn2+,
      Cd2+, Fe2+, Ni2+) inhibited the Cu2+-induced non-specific conductance increase.
      This suggests that changes in Ca2+ influx underlie this effect of Cu2+.
      Decreasing the pH or the ionic strength of external solutions also inhibited the
      Cu2+-induced plasma-membrane conductance increase. Copper was also found to
      inhibit plasma-membrane H+-ATPase activity with half-maximal inhibition occurring
      at about 5-20 micromol/l and full inhibition at about 100-300 micromol/l. The
      Hill coefficient of Cu2+ inhibition of the H+-ATPase was close to two.

PMID- 11525516
TI  - The early light-induced protein is also produced during leaf senescence of
      Nicotiana tabacum.
AB  - To better understand the genetic controls of leaf senescence, a tobacco
      (Nicotiana tabacum L. cv. SR1) mRNA that is up-regulated during senescence was
      isolated by the cDNA-amplified restriction fragment polymorphism method and the
      cDNA was cloned. The mRNA coded for the early light-induced protein (ELIP), a
      member of the chlorophyll a/b-binding protein family that has been implicated in
      assembly or repair of the photosynthetic machinery during early chloroplast
      development and abiotic stress. A protein antigenically recognized by antibodies
      to ELIP appeared during senescence with kinetics similar to those of its mRNA.
      The mRNA, designated ELIP-TOB, was detected earlier when senescence was enhanced
      by leaf detachment and treatment with 1-amino-cyclopropane-1-carboxylic acid, and
      was detected later when senescence was retarded by benzyladenine. However, no
      ELIP-TOB mRNA was seen in the dark even though senescence was accelerated under
      these conditions. Furthermore, water stress and anaerobiosis stimulated the
      appearance of ELIP-TOB mRNA before losses of chlorophyll could be detected. We
      discuss the conditions that may lead to the up-regulation of ELIP-TOB during
      senescence and speculate as to the role of the gene product in this terminal
      phase of leaf development.

PMID- 11525518
TI  - Fracture mechanics of the cell wall of Chara corallina.
AB  - Previous mechanical studies using algae have concentrated on cell extension and
      growth using creep-type experiments, but there appears to be no published study
      of their failure properties. The mechanical strength of single large internode
      cell walls (up to 2 mm diameter and 100 mm in length) of the charophyte (giant
      alga) Chara corallina was determined by dissecting cells to give sheets of cell
      wall, which were then notched and fractured under tension. Tensile tests, using a
      range of notch sizes, were conducted on cell walls of varying age and maturity to
      establish their notch sensitivity and to investigate the propagation of cracks in
      plant cell walls. The thickness and stiffness of the walls increased with age
      whereas their strength was little affected. The strength of unnotched walls was
      estimated as 47+/-13 MPa, comparable to that of some grasses but an order of
      magnitude higher than that published for model bacterial cellulose composite
      walls. The strength was notch-sensitive and the critical stress intensity factor
      K1c was estimated to be 0.63+/-0.19 MNm(-3/2), comparable to published values for
      grasses.

PMID- 11525517
TI  - Phosphate status affects the gene expression, protein content and enzymatic
      activity of UDP-glucose pyrophosphorylase in wild-type and pho mutants of
      Arabidopsis.
AB  - The effects of inorganic phosphate (Pi) deficiency on the expression of the UDP
      glucose pyrophosphorylase (UGPase) gene (Ugp), involved in sucrose
      synthesis/metabolism, and on carbohydrate status were investigated in different
      tissues of Arabidopsis thaliana (L.) Heynh. For leaves, a decrease in internal Pi
      status caused by growth of plants on a medium lacking Pi (-P conditions) led to
      an increase in the overall content of glucose and starch, but had little effect
      on sucrose content. The Pi deficiency also led to an increased carbohydrate
      content in stems/flowers, but not in roots. The expression of Ugp was upregulated
      in both leaves and roots, but not in stems/flowers. The effects of Pi status on
      Ugp expression were confirmed using leaves of both pho1-2 and pho2-1 mutants of
      Arabidopsis (Pi-deficient and Pi-accumulating, respectively) and by feeding the
      leaves with D-mannose, which acts as a sink for Pi. The Pi-status-dependent
      changes in Ugp expression followed the same patterns as those of ApS, a gene
      encoding the small subunit of ADP-glucose pyrophosphorylase, a key enzyme of
      starch synthesis. The changes in Ugp mRNA levels, depending on internal Pi
      status, were generally correlated with changes in UGPase protein content and
      enzymatic activity. This was demonstrated both for wild-type plants grown under
      Pi-deficiency and for Pi mutants. The data suggest that, under Pi-deficiency,
      UGPase represents a transcriptionally regulated step in sucrose
      synthesis/metabolism, involved in homeostatic mechanisms readjusting the
      nutritional status of a plant under Pi-stress conditions.

PMID- 11525519
TI  - Characterization of transgenic Arabidopsis thaliana with metabolically engineered
      high levels of p-hydroxybenzylglucosinolate.
AB  - The cytochrome P450 CYP79A1 catalyzes the conversion of L-tyrosine to p
      hydroxyphenylacetaldoxime, the first step in the biosynthetic pathway of the
      cyanogenic glucoside dhurrin in Sorghum bicolor (L.) Moench. We have demonstrated
      that introduction of CYP79A1 into Arabidopsis thaliana (L.) Heynh. results in the
      production of the tyrosine-derived glucosinolate p-hydroxybenzylglucosinolate (p
      OHBG), not found in wild-type A. thaliana (Bak et al., 1999, Plant J. 20: 663
      671). In the present study, glucosinolate profiles and contents in various
      tissues (roots, leaves, stems, closed flower buds and green siliques) of A.
      thaliana plants expressing CYP79A1 were analyzed by high-performance liquid
      chromatography. The total glucosinolate content in these tissues was increased
      3.5- to 4.5-fold in comparison with the level of the control plants. The increase
      was due solely to the production of p-OHBG, as the composition of the major
      endogenous aliphatic and indole glucosinolates was not affected. Conversely, in
      mature seeds the total glucosinolate content of CYP79A1 and control plants was
      similar, with p-OHBG accounting for ca. 30%. The transcript level of the
      postoxime enzyme UDP-glucose:thiohydroximate glucosyltransferase in leaves of
      CYP79A1 plants was increased ca. 50% compared with control plants, indicating
      that the post-oxime enzymes in the biosynthetic pathway are up-regulated. Western
      blot analysis and activity measurements showed similar amounts and activities of
      myrosinase in CYP79A1 and control plants. Thus, the increase in glucosinolate
      content in CYP79A1 plants was not accompanied by an increase in content or
      activity of degradation enzyme. The present data demonstrate that the high
      biosynthetic capacity of the postoxime enzymes combined with a low substrate
      specificity of the post-oxime enzymes in A. thaliana provide a highly flexible
      system for metabolic engineering of glucosinolate profiles, including new (non
      endogenous) glucosinolates derived from oximes introduced into the plant, e.g. by
      transformation with CYP79 homologues.

PMID- 11525520
TI  - Differential expression of four members of the H+-ATPase gene family during
      dormancy of vegetative buds of peach trees.
AB  - Vegetative-bud dormancy in peach (Prunus persica L. Batsch) trees is known to be
      correlated, at least partially, with properties of the underlying bud tissues
      during winter. Variations in the activity and amount of plasma-membrane H -ATPase
      were observed. A full-length cDNA, PPA2 (Prunus persica H+-ATPase 2) and three
      partial cDNAs (PPA1, PPA3 and PPA4) for the plasma-membrane H+-ATPase from peach
      trees were isolated by reverse transcription (RT)-coupled rapid amplification of
      cDNA ends (RACE) polymerase chain reaction (PCR). The accumulation of plasma
      membrane H+-ATPase transcripts was then studied in vegetative buds during
      dormancy and breaking of dormancy. Competitive RT-PCR analysis revealed that,
      during dormancy, the plasma membrane H+-ATPase transcripts were higher in the
      tissues underlying the buds than in the buds themselves. After dormancy release,
      the level of PPA1, 2, 3 mRNA increased, whereas the level of PPA4 decreased in
      the buds. When trees were kept in a greenhouse (i.e. sheltered from chilling), no
      accumulation of PPA mRNA could be detected. These results suggest that there is a
      differential accumulation of H+-ATPase mRNA between the bud and the underlying
      bud tissues during dormancy, and that chilling could act as a decisive factor.

PMID- 11525521
TI  - Glucose-6-phosphate dehydrogenase in barley roots: kinetic properties and
      localisation of the isoforms.
AB  - Two different isoforms of glucose-6-phosphate dehydrogenase (Glc6PDH; EC
      1.1.1.49) have been partially purified from barley (Hordeum vulgare L., cv.
      Alfeo) roots. The procedure included an ammonium sulfate step, Q-Sepharose and
      Reactive Blue agarose chromatography, and led to 60-fold and 150-fold
      purification for the two enzymes, respectively. The Glc6PDH 1 isoform accounts
      for 17% of total activity of the enzyme in roots, and is very sensitive to the
      effects of NADP+/NADPH ratio and dithiothreitol; the Glc6PDH 2 isoform is less
      affected by reducing power and represents 83% of the total activity. The isoforms
      showed distinct pH optima, isoelectric points, Km for glucose-6-phosphate and a
      different electrophoretic mobility. The kinetic properties for the two enzymes
      were affected by ATP and metabolites. Both enzymes are inhibited to different
      extents by ATP when magnesium is omitted from the assay mixture, whereas the
      addition of ATP-Mg2+ had no effect on Glc6PDH activities. The Glc6PDH isoforms
      are usually present in the plastids and cytosol of plant cells. To verify the
      intracellular locations of the enzymes purified from barley roots, Glc6PDH was
      purified from isolated barley root plastids; this isoform showed kinetic
      parameters coincident with those found for Glc6PDH 1, suggesting a plastid
      location; the enzyme purified from the soluble fraction had kinetic parameters
      resembling those of Glc6PDH 2, confirming that this isoform is present in the
      cytosol of barley roots.

PMID- 11525522
TI  - Enhanced disease resistance conferred by expression of an antimicrobial magainin
      analog in transgenic tobacco.
AB  - Magainins are a group of short peptides originally isolated from frog skin and
      thought to function as a natural defense mechanism against infection due to their
      antimicrobial properties. The engineered magainin analog peptide Myp30 was found
      to inhibit spore germination of the oomycete, Peronospora tabacina (Adam) in
      vitro, and the growth of a bacterial pathogen Erwinia carotovora subsp.
      carotovora (Jones). Transgenic tobacco (Nicotiana tabacum L.) plants expressing
      Myp30 were evaluated for resistance to these pathogens. The expression of the
      peptide only to an extracellular location resulted in significant reduction in
      sporulation and lesion size due to P. tabacina infection. A significant increase
      in resistance to the bacterial pathogen was also observed regardless of the
      targeting location of the peptide.

PMID- 11525523
TI  - Adolescents at risk for mistreating their children. Part I: Prenatal
      identification.
AB  - OBJECTIVE: To determine if the Family Stress Checklist helps prenatal care
      providers identify adolescents who are at risk for mistreating their children.
      METHODS: We studied 262 participants in a comprehensive, adolescent-oriented
      maternity program. During the prenatal period, the Family Stress Checklist was
      used to quantify abuse potential, with scores >25 defining high risk. Information
      about the social context of the pregnancy and the pattern of health care
      utilization was obtained with a self-administered questionnaire, and by reviewing
      the medical records. Major disruption of primary care giving by the adolescent
      mother was classified hierarchically as abuse, neglect, and abandonment. RESULTS:
      Family Stress Checklist scores ranged from 0 to 65 (mean + SD = 20.1 + 1.4); 113
      (43%) of the 262 teenagers were classified as high risk. High and low risk
      adolescent mothers made an equivalent number of health maintenance and Emergency
      Department visits, but the high risk group initiated significantly more acute
      care visits (6.0 + 4.1 compared to 3.9 + 3.3; p < .0001). After controlling for
      pre-existing sociodemographic differences, high risk 1-year-olds were 8.41 (95%
      CI: 1.77-40.01) times and high risk 2-year-olds 5.19 (95% CI: 1.99-13.60) times
      more likely to have been mistreated than their low risk counterparts.
      CONCLUSIONS: Prenatal care providers can use the Family Stress Checklist to
      systematically identify a subgroup of adolescent mother whose excessive use of
      the acute medical care services and propensity for mistreating their children
      suggests the need for additional support services.

PMID- 11525524
TI  - Adolescents at risk for mistreating their children. Part II: A home- and clinic
      based prevention program.
AB  - OBJECTIVE: To determine if adding an intensive home visitation component to a
      comprehensive adolescent-oriented maternity program prevents child abuse and
      neglect. METHODS: We studied 171 participants in a comprehensive, adolescent
      oriented maternity program who were deemed to be at high risk for child abuse and
      neglect. Half were randomly assigned to receive in-home parenting instruction.
      Major disruptions of primary care-giving by the adolescent mother were classified
      hierarchically as abuse, neglect, and abandonment. RESULTS: Compliance with home
      visits varied in relation to the support the teenage mothers received from their
      families and the fathers of their babies (p < .0001). There were no significant
      treatment group differences in the pattern of health care utilization, the rate
      of postpartum school return, repeat pregnancies, or child abuse and neglect. The
      incidence of maltreatment rose in tandem with the predicted risk status of the
      mother. Ultimately, 19% of the children were removed from their mother's custody.
      CONCLUSIONS: Prediction efforts were effective in identifying at-risk infants,
      but this intensive home- and clinic-based intervention did not alter the
      incidence of child maltreatment or maternal life course development. A parenting
      program that was more inclusive of the support network might be more popular with
      teenagers and therefore more effective. Our findings also emphasize the
      importance of including counseling specifically designed to prevent teenagers
      from abandoning their children.

PMID- 11525525
TI  - Binge and purge behavior among adolescents: associations with sexual and physical
      abuse in a nationally representative sample: the Commonwealth Fund survey.
AB  - OBJECTIVES: (1) To examine associations between binge and purge behavior and
      sexual and physical abuse among adolescents; (2) to determine if these
      associations remain significant after controlling for sociodemographic and
      anthropometric characteristics; and (3) to identify aspects of abuse associated
      with binge and purge behavior. METHOD: A nationally representative sample of 6728
      adolescents in 5th-12th grades completed the Commonwealth Fund Survey of the
      Health of Adolescent Girls and Boys. RESULTS: Binge and purge behavior was nearly
      twice as prevalent among girls (13%) as boys (7%), and was significantly
      associated with all abuse types (physical, sexual, or both). Associations were
      strongest among individuals who had experienced both physical and sexual abuse
      [odds ratios 4.28 (girls) and 8.25 (boys)]. Differences in binge and purge
      behavior by gender and type of abuse across abuse characteristics were limited. A
      higher percentage of abused youth that did not discuss their abuse reported binge
      purge behavior than those who did discuss their abuse. Abused girls and boys who
      did talk to someone about the abuse most often discussed the abuse with their
      best friend (42.5% and 18.0%, respectively), their mother (38.8% and 32.2%,
      respectively), and their friends (27.2% and 19.5%, respectively). DISCUSSION:
      Being physically and/or sexually abused was associated with greater likelihood
      for engaging in binge and purge behaviors. Discussing the abuse experience with
      another person may help to reduce binge-purge behavior, as abused adolescents who
      did not discuss the abuse were more likely to report binge-purge behavior than
      those who did discuss their abuse.

PMID- 11525526
TI  - Antecedents and socioemotional consequences of physical punishment on children in
      two-parent families.
AB  - OBJECTIVE: The main objective of this study was to test a structural model of the
      antecedents and socioemotional consequences of mothers' use of physical
      punishment on children in two-parent families. METHOD: Mother-child data from the
      National Longitudinal Survey of Youth, based on a sample of 1397 4- to 9-year-old
      children, were used to test a structural model derived by the author from
      previous research. The hypothesized model was revised; the revised model was
      cross validated on a split-half sample, and estimated separately by age group,
      gender, and race/ethnicity. RESULTS: The revised model fit the data well and was
      supported by cross-validation. Poverty, maternal birth age, parents' education,
      maternal depression, and marital conflict were directly or indirectly related to
      mothers' frequent use of physical punishment. Frequent use of physical punishment
      was directly related to children's socioemotional problems, as were maternal
      depression and marital conflict. Few subgroup differences were found.
      CONCLUSIONS: Main findings indicate that the effect of poverty on mothers' use of
      physical punishment is indirect, and is mediated by maternal depression and
      marital conflict. Depressed mothers spank their children more frequently and
      experience higher levels of marital conflict, which, in turn, is directly related
      to their use of physical punishment. Younger, more educated mothers spank their
      children less often. Children who are spanked more frequently exhibit more
      socioemotional problems.

PMID- 11525527
TI  - The role of family preservation therapists in facilitating use of aftercare
      services.
AB  - OBJECTIVE: The aims were to: (1) examine the process that family preservation
      therapists use when developing and implementing aftercare plans, and (2) examine
      how family preservation therapists perceive the availability and accessibility of
      community services that families need after short-term family preservation
      services. METHOD: Focus groups were conducted with therapists (n = 26) from five
      agencies that provide family preservation services in a large Midwest city. One
      agency was the local public child welfare agency, and the other four were
      nonprofit agencies with state contracts to provide family preservation services.
      RESULTS: Therapists viewed aftercare services as important and necessary, yet
      perceived barriers to families' use of aftercare services. Therapists undertook a
      number of activities to help families access and use services, though some
      therapists took a less active role than others did in helping families link to
      services. It was perceived that more follow-up was needed to ensure service use.
      Participants viewed certain services as especially difficult to access or
      unavailable, including services for men and adolescents. CONCLUSIONS: More
      explicit and focused attention to facilitating service use is needed. This can be
      accomplished by therapists focusing on service use during assessment and
      treatment planning. Regular follow-ups after short-term family preservation
      services for the purpose of helping families to productively use services may be
      needed. However, systemic changes are also needed to ensure that needed services
      are available and accessible.

PMID- 11525528
TI  - A survey on parent-child conflict resolution: intrafamily violence in Italy.
AB  - OBJECTIVE: The purpose of this paper was to investigate factors associated with
      intrafamily violence toward children in Italy. Family structure and the
      characteristics of both caretakers and children were explored. Their association
      with the incidence of minor and severe violence was analyzed to test the
      hypothesis that child physical abuse is related to a combination of different
      factors involving the family as a whole. METHOD: This research was carried out by
      submitting an anonymous questionnaire to 2388 families residing in Tuscany,
      Italy. The form included two sections, one related to the family cultural
      substrate, and to potentially influential events affecting the family during the
      year 1998. The other one, taken from the conflict tactics (CT) scales, presented
      a hierarchy of possible responses to conflict. RESULTS: Physical punishment
      appeared to be a general behavior in Italy, because the incidence of minor
      violence was 77%. The incidence of severe violence was about 8%. When considering
      family, caretaker, and child characteristics mostly associated with physical
      punishment in Italy, we found that families with a low income, where caretakers
      had health problems or were stressed, and with younger and more "problematic"
      children presented the highest risk of intrafamily violence during conflict
      resolution. CONCLUSIONS: The results point to the importance of a balance between
      potentiating and compensatory factors in complex and dynamic relationships among
      family members, to avoid strategy resolution of conflict ultimately leading to
      violence. Moreover, minor and severe violence appeared to be two related but
      different phenomena.

PMID- 11525529
TI  - Errorless compliance training with physically abusive mothers: a single-case
      approach.
AB  - OBJECTIVE: "Errorless compliance training" is a recently developed, success-based
      approach for teaching children to comply with parental requests without the use
      of coercive consequences. Two mothers were trained to use this intervention to
      reduce severe child defiance that was precipitating mother/child confrontations
      and physical abuse. METHOD: To determine probability of child compliance to
      specific requests, we observed mothers delivering requests to their child. We
      then developed a hierarchy of compliance probabilities for each child. Mothers
      were trained to deliver a high density of Level 1 requests (those that typically
      yielded compliance), and provide praise for child compliance. Lower probability
      request levels were introduced gradually, at a slow enough pace to preclude
      noncompliant responses, reducing the need for mothers to respond aversively to
      child behavior. RESULTS: At treatment completion and follow-up, both children
      demonstrated substantial improvements in compliance. CONCLUSIONS: The errorless
      approach may be well suited to managing parenting deficits and child opposition
      commonly associated with family violence.

PMID- 11525530
TI  - Has arteriography gotten a bad name? Current accuracy and morbidity of diagnostic
      contrast arteriography for aortoiliac and lower extremity arterial disease.
AB  - Recently, contrast arteriography has been challenged as the diagnostic test of
      choice for lower extremity arterial disease because of its associated morbidity
      and questionable accuracy in identifying suitable distal outflow arteries. The
      purpose of this report was to analyze our experience to determine if these
      concerns were justified. We reviewed 500 consecutive contrast arteriograms
      performed at our hospital for aortoiliac and lower extremity arterial disease
      between November 1994 and November 1998. Arteriograms performed in conjunction
      with therapeutic procedures such as balloon angioplasty, stent placement, and
      thrombolysis were excluded, leaving 244 diagnostic cases for analysis. Forty-six
      percent (112) of patients had diabetes mellitus, 14% (34) had an elevated
      baseline serum creatinine (> or =1.5 mg/dL), and an additional 7% (17) were
      dialysis dependent. Radiologists limited contrast volume by imaging only the
      symptomatic extremity when appropriate and using digital subtraction techniques
      as indicated. Our results showed that diagnostic contrast arteriography is
      associated with an acceptably low morbidity, has an accuracy that is unlikely to
      be surpassed by other modalities, and remains the diagnostic test of choice for
      lower extremity arterial disease.

PMID- 11525531
TI  - Experimental treatment of vascular graft infection due to Staphylococcus
      epidermidis by in situ replacement with a rifampin-bonded polyester graft.
AB  - In situ prosthetic graft replacement (ISPGR) of an infected prosthesis raises the
      risk of recurrent infection in the new graft, especially in cases involving drug
      resistant microorganisms. The purpose of this animal study was to evaluate in
      situ replacement of a vascular graft infected by a highly rifampin-resistant
      strain of Staphylococcus epidermidis with the use of a rifampin-bonded polyester
      graft. Antibiotic bonding was obtained by soaking grafts in a high dose of
      rifampin solution (60 mg/mL). The infrarenal abdominal aorta of 20 dogs was
      replaced using a polyester prosthesis infected with a highly rifampin-resistant
      strain of Staphylococcus epidermidis. One week later, the 18 surviving animals
      were randomized into three groups. Group I (n = 6) did not undergo reoperation.
      Group II (n = 6) underwent ISPGR using a rifampin-bonded prosthesis. Group III (n
      = 6) underwent ISPGR using an untreated prosthesis. All surviving animals were
      killed 28 days after the first procedure. Infectious signs were noted and
      bacteriological study was carried out on explanted prostheses and various tissue
      samples. The findings of this experimental study show that soaking a polyester
      prosthesis in a high-dose rifampin solution can prevent reinfection after in situ
      replacement of a prosthesis infected by a highly rifampin-resistant
      Staphylococcus epidermidis.

PMID- 11525532
TI  - Treatment of deep infection following thoracic aorta graft replacement without
      graft removal.
AB  - Deep infection following thoracic aortic replacement constitutes an extremely
      serious and life-threatening complication, and its treatment remains a challenge
      to surgeons. We report our experience involving five patients in whom deep
      infection occurred around the graft. Four of the five patients were treated by
      emergency surgery and one was treated by elective surgery. Surgical procedures
      performed including hemiarch replacement in one case, total arch replacement in
      one case, suspension of aortic valve and ascending aorta replacement in one case,
      Bentall procedure in one case, and descending aorta re-replacement in one case.
      Methicillin-resistant Staphylococcus aureus was detected in four patients,
      methicillin-resistant Staphylococcus epidermidis in one, and Aspergillus in one
      patient from purulent discharge at the operative site. Reoperative debridement
      and irrigation drainage were carried out at an early phase of infection.
      Intermittent irrigation following the reoperation was performed in all cases. In
      addition, muscle flap filling or omental translocation was carried out in three
      patients. Although the reported principle of treatment for arterial graft
      infection is extraanatomical bypass or rereplacement after removal of the
      infected graft, such procedures may be technically difficult and have a high risk
      at the thoracic level. Local anti-septic irrigation, administration of
      antibiotics, and vascular-rich tissue filling are useful procedures, and it
      appears that it is not always necessary to remove prosthetic grafts.

PMID- 11525533
TI  - The effect of supplemental oxygen on the transarterial wall oxygen gradients at a
      prosthetic vascular graft to artery anastomosis in the rabbit.
AB  - Artery wall hypoxia has been proposed to contribute to many kinds of artery wall
      pathology, including atherosclerosis and intimal hyperplasia. The purpose of this
      study was to determine the effect of supplemental oxygen on the transarterial
      wall oxygen gradients at a prosthetic vascular device (PVG)-to-artery
      anastomosis. The transarterial wall oxygen gradient in the infrarenal aorta of
      New Zealand White rabbits housed for 42 days in a 40% supplemental oxygen was
      measured with an oxygen microelectrode 2 mm distal to a PVG-to-artery
      anastomosis. Oxygen tensions were significantly increased throughout the artery
      wall at all time points in the supplemental oxygen groups compared to those in
      non-oxygen-supplemented groups. Within the oxygen-supplemented groups, the outer
      artery wall had diminished oxygen tensions immediately following creation of the
      anastomosis, with a slow return to control oxygen tensions on postanastomosis day
      42 which correlated with a return of the vasa vasorum. These changes were noted
      without differences in blood pressure or arterial blood oxygen concentrations
      within the oxygen-supplemented group. Artery wall hypoxia noted following the
      creation of a PVG-to-artery anastomosis can be eliminated and artery wall oxygen
      tensions significantly increased by the administration of supplemental oxygen.

PMID- 11525534
TI  - Is there a role of angiotensin-converting enzyme gene polymorphism in the failure
      of arteriovenous femoral shunts for hemodialysis?
AB  - In humans, thrombosis and neointimal hyperplasia are the major factors
      responsible for prosthetic graft occlusion. Previous studies suggest that the
      renin-angiotensin system is one of the key enzymes in the vascular system and has
      been implicated in the pathogenesis of thrombosis and neointimal hyperplasia. We
      conducted a case-control study to determine the frequency of the different
      angiotensin-converting enzyme (ACE) genotypes among the patients who had PTFE
      graft implantation for hemodialysis access. Between 1997 and 1999, 30 graft
      implantations were performed. Twelve individuals (40%) developed thrombotic
      complications, 8 of the 12 patients had ACE ID polymorphism, and 2 patients had
      DD and 2 patients had II polymorphism. The ID polymorphism was significantly more
      frequent in the thrombosed arteriovenous (A-V) grafts than in nonthrombosed A-V
      grafts (chi2 = 7.57 and p = 0.02). Overall, the frequency of the D and I alleles
      was 66.6 and 33.3%, respectively. In conclusion, ID polymorphism of the ACE gene
      plays an important role in the pathogenesis of vascular access thrombosis in
      subjects undergoing hemodialysis for chronic renal failure.

PMID- 11525535
TI  - Characterization of renal parenchymal perfusion during experimental infrarenal
      aortic clamping and declamping with enhanced thermodiffusion electrodes.
AB  - Despite multiple previous experimental and clinical investigations, it has not
      been fully clarified until now whether infrarenal aortic cross-clamping (IRAC)
      induces a significant disturbance of renal parenchymal perfusion. Most renal
      cortical flow data collected thus far have been heterogenous because of inherent
      limitations of available measurement technology. The enhanced thermal diffusion
      (TD) electrode is a newly developed and previously validated prototype device
      that allows continuous quantification of parenchymal kidney perfusion after local
      probe implantation. We monitored renal perfusion during experimental IRAC with TD
      for the first time, thereby also evaluating the potential applicability of the
      method in clinical aortic surgery. IRAC (20 min) followed by sudden declamping
      was performed in pigs under general anesthesia (n = 14). Renal cortical blood
      flow (RCBF) was continuously quantified by TD, total aortic flow (TABF) and renal
      artery flow (RABF) were measured by ultrasonic flow probes, and parameters of
      systemic circulation were determined by Swan-Ganz catheter. Our results showed
      that kidney perfusion can be continuously quantified using TD electrodes during
      experimental aortic surgery in a porcine model. IRAC does not lead to a
      significant impairment of RCBF in young pigs as measured by TD. Renal perfusion
      appears to be predominantly pressure driven. Consequently, abrubt aortic
      declamping can bring about prolonged renal ischemia. Transfer of the TD method to
      RCBF monitoring during clinical aortic surgery appears to be feasible and should
      be investigated in selected cases.

PMID- 11525536
TI  - Postoperative morbidity of closely staged bilateral carotid endarterectomies: an
      intersurgical interval of 4 days or less.
AB  - The purpose of this study was to determine if there is increased morbidity and
      mortality with bilateral carotid endarterectomies (CEAs) done with an
      intersurgical period of less than 4 days compared to historical groups of
      unilateral CEAs, or those with a greater intersurgical delay. From January 1991
      to July 1998, 1390 carotid endarterectomies were performed, of which 154 (11.1%)
      were closely staged bilateral CEAs. Seventy-seven patients (51 male, 26 female;
      mean age 72.5 years) underwent bilateral CEAs within 4 days or less. Immediate
      and 30-day postoperative morbidity, including neurologic deficits, cranial nerve
      deficits, and mortality, were documented. Although controversial, there is no
      increased morbidity or mortality with bilateral CEAs done with an intersurgical
      delay of less than 4 days, when compared to the unilateral CEA historical groups.

PMID- 11525537
TI  - Advantages of a single-stop vascular assessment clinic.
AB  - We have examined the impact of a single-stop vascular assessment clinic,
      incorporating a portable Toshiba SSA140 color flow Doppler, scanner, on patient
      pathways and throughput in a teaching hospital. Data were collected
      retrospectively from computer-held information for a 3-month period in a
      conventional vascular clinic and compared with data from the equivalent 3 months
      after establishment of a single-stop clinic. New and follow-up patient numbers,
      discharges, and outcome of each consultation were compared. The results showed
      that the establishment of a single-stop vascular assessment clinic with duplex
      Doppler ultrasound facilitated earlier diagnosis and instigation of treatment. It
      also indirectly reduced clinic numbers, allowing a greater proportion of new-to
      old patients per session. It is more convenient and cost-effective for patients
      and hospitals.

PMID- 11525538
TI  - Calciphylaxis, a poorly understood clinical syndrome: three case reports and a
      review of the literature.
AB  - Systemic calcification syndromes are a recognized complication occurring in some
      patients with end-stage renal disease (ESRD) and secondary hyperparathyroidism.
      These patients develop severe livedo reticularis and subcutaneous tissue lesions
      progressing to frank necrosis and ultimately large areas of eschar. Clinically
      this syndrome is known as calciphylaxis; these lesions are usually resistant to
      aggressive debridement, systemic antibiotics, and revascularization procedures.
      We report three patients with somewhat different clinical presentations but all
      sharing a common link of exquisitely painful leg ulcers initially being treated
      as ischemic lesions or venous stasis-type ulcerations. These three patients were
      diagnosed with calciphylaxis on the basis of clinical, biochemical, and
      histopathological criteria. Two patients underwent parathyroidectomy late in the
      progression of their disease, with some resolution of their ulcerative lesions.

PMID- 11525539
TI  - Stent graft repair for rupture of the subclavian artery secondary to infection of
      a subclavian-to-carotid bypass graft.
AB  - The case of anastomotic rupture of the subclavian artery following infection of a
      subclavian-to-carotid bypass grafting is reported. Emergency endoluminal stent
      graft repair was life saving and aided wound healing, but stent graft thrombosis
      occurred. Such a complication raises some concern about the safety of this
      procedure in an infected setting. The use of autologous saphenous vein-covered
      stent graft may provide some advantages in avoiding graft infection and
      thrombosis.

PMID- 11525540
TI  - Infected aortic pseudoaneurysm following laparoscopic cholecystectomy.
AB  - A 38-year-old hemodialysis-dependent diabetic female patient underwent a
      laparoscopic cholecystectomy for symptomatic cholelithiasis. Postoperatively, she
      developed chronic back pain. Eight months following laparoscopic cholecystectomy,
      she developed fevers and recurrent bacteremia with methicillin-resistant
      Staphylococcus aureus, despite removal of all indwelling intravenous dialysis
      access. An abdominal CT scan demonstrated a 7-cm pseudoaneurysm extending from
      the right anterolateral lower abdominal aorta. Following resection of her
      infected aneurysm and extraanatomic bypass, she cleared her bacteremia and
      recovered. This first report of an aortic pseudoaneurysm following laparoscopic
      cholecystectomy is presented in the context of other vascular complications
      reported following the same procedure.

PMID- 11525541
TI  - Ureteral injury during aortic aneurysm repair by the retroperitoneal approach.
AB  - Three ureteral injuries (two proximal, one middle) associated with
      retroperitoneal repair of aortic abdominal aneurysms are reported. The authors
      believe these represent traction injuries that are related to the use of
      stationary retractors and suggest that complete anterior mobilization of the left
      kidney from its posterior fossa will decrease the odds of such an injury.

PMID- 11525542
TI  - Multiple venous aneurysm of a basilic vein.
AB  - An uncommon case of multiple venous aneurysm of the basilic vein was diagnosed in
      a 61-year-old woman who presented with a left arm mass. The lesion was
      successfully resected with day surgery. Clinical features, including the
      complications, treatment, and etiology of these exceedingly uncommon lesions, are
      discussed.

PMID- 11525543
TI  - Extended repair of thoracic aorta through left thoracotomy after aortic root
      replacement.
AB  - A patent distal false lumen after repair of type A aortic dissection often poses
      serious late complications. We present a successful repair of dissecting aortic
      aneurysm through left thoracotomy, extending from the ascending to descending
      thoracic aorta after composite graft replacement of the aortic root. Although
      staged operations, including the elephant trunk procedure, are usually chosen for
      remaining extensive aortic disease after replacement of the aortic root or the
      ascending aorta, a single-stage repair from the ascending to the descending
      thoracic aortas through left thoracotomy can be a favorable option to treat a
      patient with this type of aortic disease.

PMID- 11525544
TI  - Current status of surveillance of hemodialysis access grafts.

PMID- 11525545
TI  - Retrograde aortomesenteric bypass with tunneling behind the left renal pedicle.
AB  - This report describes a new technique for revascularization of the superior
      mesenteric artery (SMA) which creates a retrograde bypass tunneled behind the
      left renal pedicle. The procedure can be performed by the left retroperitoneal or
      transperitoneal route, alone or in association with reconstruction of the
      infrarenal aorta. Proximal anastomosis is retrograde on the left side of the
      infrarenal aorta or aortic prosthesis. The course of the bypass runs first in the
      back and top of the retrorenal dissection plane, then loops behind and over the
      left renal pedicle, and finally turns downward and forward to the SMA. Distal
      anastomosis can be made either end-to-end or end-to-side. This large, loop-shaped
      course not only reduces the risk of kinking but also gives the bypass enough
      length to adapt to movements of the SMA. This technique has been performed in
      association with reconstruction of the infrarenal aorta in three patients.
      Postoperative control using Doppler ultrasound, arteriography, and helical CT
      scan showed no kinking or other abnormality. One patient died a month after the
      procedure from myocardial infarction. Follow-up Doppler ultrasound in the two
      surviving patients showed bypass patency with no stenosis at 19 and 30 months.

PMID- 11525546
TI  - Optometrist or specialist?

PMID- 11525547
TI  - A weighted version of the Melbourne Low-Vision ADL Index: a measure of disability
      impact.
AB  - OBJECTIVE: To develop a version of the Melbourne Low-Vision ADL Index that
      measures the personal impact of disability in activities of daily living (ADL's).
      Also, to determine the relationship between clinical measures of vision
      impairment and disability impact. METHODS: The Melbourne Low-Vision ADL Index
      (MLVAI) is a desk-based clinical assessment of disability in ADL's. Ability to
      perform each item is rated on a five-level descriptive scale from zero to four.
      In this study, the original version of the MLVAI was modified to measure
      disability impact. The simple modification involved weighting each item by the
      importance of that item to the person being tested. Importance was also rated on
      a five-level scale from zero to four. The validity and reliability of the
      Weighted Melbourne Low-Vision ADL Index (MLVAI(W)) was determined for 97 vision
      impaired subjects in a cross-sectional study. RESULTS: Cronbach's alpha
      coefficient indicated an internal reliability of 0.94, and an intraclass
      correlation coefficient indicated an overall reliability of 0.88. The standard
      error of measurement was 24.7 points (out of a possible score of 400). There was
      a statistically significant difference in test scores between normal subjects and
      vision-impaired subjects. All vision measures had a high, statistically
      significant correlation with MLVAI(W) score. Near-word acuity had the strongest
      correlation (r(s) = 0.78, p < 0.001), followed by Melbourne Edge Test contrast
      sensitivity (r(s) = -0.72, p < 0.001). Visual field had the weakest correlation
      (r(s) = -0.52, p < 0.001). The best predictive model of MLVAI(W) score
      incorporated the variables age, near-word acuity, and visual field. Together,
      these variables accounted for 65.1% of the variance in MLVAI(W) score.
      CONCLUSIONS: The MLVAI is highly valid and reliable when weighted by a scale that
      reflects the personal importance of ADL's. The MLVAI(W) can provide information
      over and above that obtained with the usual clinical vision measures and may be
      used to assess low-vision patients and to measure low-vision rehabilitation
      outcomes. It is suggested that the assessment of disability using the original
      MLVAI and the assessment of the impact of disability using the MLVAI(W) should be
      kept separate to facilitate the clear interpretation of the outcomes of low
      vision rehabilitation.

PMID- 11525548
TI  - The interoccasion repeatability of intraocular pressure measurement using the
      Tono-Pen in a sample of school-aged children.
AB  - PURPOSE: The purpose of this study was to assess the interoccasion repeatability
      of the Tono-Pen XL portable applanation tonometer in school-aged children.
      METHODS: Thirty-one normal children were recruited from The Ohio State College of
      Optometry Pediatric Clinic. They ranged in age from 6 to 14 years. Intraocular
      pressure was measured using the Tono-Pen XL in both eyes of all subjects on two
      different occasions within a median of 9 days. Refractive error was measured by
      noncycloplegic autorefraction. Data from right eyes only are presented. RESULTS:
      There was no average difference in the intraocular pressure between occasions.
      The 95% limits of agreement between occasions were -5.58 to 4.87 mm Hg.
      CONCLUSIONS: The Tono-Pen XL gives reasonably repeatable readings between
      occasions in school-aged children.

PMID- 11525549
TI  - Color discrimination in heterozygous deutan carriers.
AB  - PURPOSE: The color discrimination abilities of heterozygous deutan female
      carriers were measured using color mixture thresholds and compared with those of
      suspected nonheterozygous normal subjects. METHODS: Eight test subjects and 26
      control subjects were run on a computer-controlled color test (color mixture
      thresholds) that presented 1 degree diameter spots on a color television monitor
      for 1/60 of a second. A QUEST procedure was used to determine visual thresholds
      for spots varying in brightness and/or color. Individual data points were graphed
      on an X/Y plot and fitted with an ellipse. The major and minor diameters of the
      ellipse represent the color and brightness thresholds, respectively. RESULTS: The
      mean axis angle of the ellipse for the heterozygous carriers did not differ from
      that for the controls (15.75 degrees vs. 14.93 degrees, p = 0.428, Mann-Whitney
      test). The carriers did show, however, a larger mean major axis length (68.79 vs.
      46.78, p = 0.0218, Mann-Whitney test). Additionally, the length-to-width ratios
      for the carriers were higher than the controls (9.34 vs. 6.80, p = 0.0403, Mann
      Whitney test). CONCLUSIONS: Deutan-carriers do show reduced color purity
      discrimination as measured using color mixture thresholds compared with
      nonheterozygous, color vision normals.

PMID- 11525550
TI  - A comparison of two methods of evaluating cornea-to-contact lens base curve
      fluorescein patterns in keratoconus.
AB  - PURPOSE: The purposes of the study were as follows: (1) to compare the apical
      fitting relationship of habitual contact lens fluorescein patterns in keratoconus
      as determined by clinician assessment of on-eye patterns to those determined by
      photograph readers looking at slides of fluorescein patterns and (2) to determine
      the validity of the techniques used in assessing the apical fitting relationships
      of rigid corneal contact lenses on keratoconic corneas. METHODS: Central
      fluorescein patterns of rigid contact lens-wearing keratoconus patients enrolled
      in the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study were
      graded as "definite touch," "touch," "clearance," or "definite clearance" by
      certified clinicians. Photographs of these patterns were evaluated independently
      by certified, masked photograph readers using the same grading scale. RESULTS:
      Agreement between "re-reads" of the same fluorescein pattern slides by the
      photograph readers was substantial (weighted kappa = 0.751). Agreement between
      assessments of habitual fit fluorescein patterns at the baseline vs. the repeat
      visits was poor for the photograph readers (weighted kappa = 0.254) and moderate
      for the clinicians (kappa = 0.480). Agreement between clinicians' and photograph
      readers' assessment of the habitual contact lens fluorescein pattern at the
      baseline visit was fair (weighted kappa = 0.382). CONCLUSIONS: Repeatability and
      validity of this technique were fair to excellent. Many factors influence
      fluorescein pattern interpretation, and improvement of the objective method of
      fluorescein pattern assessment by photograph readers will require improved
      methodology that takes these factors into consideration.

PMID- 11525551
TI  - Precision of three topography instruments in keratoconus subjects.
AB  - PURPOSE: To determine the test-retest reliability of three popular and
      commercially available Placido-ring videokeratography instruments in subjects
      with keratoconus. METHODS: Nine subjects (16 eyes) with keratoconus of varying
      degrees of severity had up to four images per eye generated, in random order,
      from the EyeSys Model II, Dicon CT 200 and the Keratron Corneal Analyzer. Test
      retest analyses for the images were sampled at four locations: 1.5 mm nasal,
      inferior, temporal, and superior from center. The average standard deviation of
      all points was used to determine the short-term variability of the measurements.
      RESULTS: The short-term variability (in diopters) of the Dicon, EyeSys, and
      Keratron was 0.61 to 3.31 D, 0.94 to 1.51 D, and 0.58 to 2.85 D, respectively,
      for axial distance maps and 1.07 to 6.82 D, 0.79 to 1.77 D, and 1.23 to 3.03 D
      for tangential curvature maps. CONCLUSION: Results support the notion of a loss
      in repeatability for all three instruments when corneal irregularity is present,
      which reduces test-retest reliability.

PMID- 11525553
TI  - Effects of microwave irradiation on the parameters of hydrogel contact lenses.
AB  - Ten brands of hydrogel contact lenses were selected from five of the six British
      Approved Name lens classification groups to test in vitro the effects of repeated
      heat disinfection by means of microwave irradiation. Each lens type was tested
      over a number of cycles corresponding to its scheduled number of wearing days.
      The total diameter and back vertex power of all 80 test and 12 control lenses
      were measured at the end of their relevant cycling period. The back optic zone
      radius, center thickness, and water content were measured for 40 test and 8
      control lenses. No clinically significant change was found in any of the 10
      brands tested. Statistically significant changes were found in the back optic
      zone radius of the Frequency 55 group and water content of the Precision UV
      group. Some discoloration was noted in Ciba Visitint lenses.

PMID- 11525552
TI  - Clinical trial of a patient-operated microwave care system for hydrogel contact
      lenses.
AB  - The clinical effects of a patient-operated system of microwave disinfection for
      soft contact lenses were assessed in a prospective pilot trial involving 103
      patients who were drawn from five optometric practices. Fifty-six subjects used
      the test system for 1 month, and 13 subjects continued use for a total of 3
      months. Both test and control subjects were examined for clinical signs using
      slitlamp tests. After 1 month, the incidence of all signs reported in the
      microwave group was not significantly greater than in the control group (p =
      0.267), and the same was true after 3 months (p = 0.214). There was a
      significantly greater incidence of edema in the 1-month test group and of
      staining in the control group. UV spectroscopic examination of worn lenses from
      test subjects exhibiting significant signs did not show a higher level of
      deposition than on lenses worn by control subjects (p = 0.397).

PMID- 11525555
TI  - Lentivirus vectors: difficulties and hopes before clinical trials.
AB  - The ability to transduce non-dividing cells is a unique feature of lentiviruses
      which distinguishes them from simple retroviruses. This feature was the major
      incentive for the development of the lentivirus vector system. Lentivirus vectors
      can deliver and integrate > 8 kb of transgenic DNA into target cell genomes
      without inducing a host immune response against the transduced cells. Thus
      lentivirus vector-based gene delivery can be considered the most efficient method
      by which transgenes can be incorporated into the host cell genome and maintain
      long-term expression. This review describes the major developments in the
      lentivirus vector system, which significantly improve vector biosafety, vector
      production and transgene expression. The success and difficulties in reverting
      disease phenotypes by lentivirus vectors carrying therapeutic genes in various
      animal models including beta-thalassemia and Parkinson's disease and the
      implications of these studies for future gene therapy clinical trials are also
      discussed.

PMID- 11525554
TI  - Diminished spatial summation contributes to the age deficit in the discrimination
      of low-contrast vernier oscillation.
AB  - PURPOSE: This study sought to determine whether a decline in spatial summation
      contributes to age-related deficits on oscillatory displacement thresholds
      (ODT's). A secondary goal was to evaluate the extent of spatial summation on a
      dynamic version of vernier hyperacuity. METHODS: The ODT's and contrast
      sensitivity functions (CSF's) of optimally corrected young and old observers were
      compared as a function of vernier target length (4, 8, or 32 min), contrast level
      (5 or 30%), and oscillation rate (2 or 8 Hz). RESULTS: Age deficits on ODT's were
      related directly to rate of oscillation, but not target contrast. No age
      difference was seen in ODT's for short low-contrast targets; as target length
      increased thresholds improved more rapidly for young than old observers; this
      pattern was reversed at high contrast. ODT's were related strongly and
      consistently to contrast sensitivity for old but not young observers.
      CONCLUSIONS: Diminished spatial summation appears to contribute to the aging
      visual system's loss of temporal discrimination for low contrast oscillating
      targets. Spatial summation contributes more importantly to the displacement
      discrimination of oscillating than to static vernier targets.

PMID- 11525556
TI  - Targeted gene correction strategies.
AB  - We are now approaching the reality of success in gene therapy as our knowledge of
      the genetic basis of disease continues to grow, coupled with improved delivery
      methods for therapeutic nucleic acid molecules. It is apparent that gene therapy
      can be divided into two specific and very different approaches in which gene
      replacement, or augmentation, is differentiated from gene repair. In fact, gene
      augmentation is characterized by the delivery of the coding sequence of the gene
      of interest in an expression cassette. In contrast, gene repair differs in that
      the process targets for correction of the mutation responsible for the genetic
      disorder. The in situ repair of a gene has many advantages over conventional
      replacement methods. This review will concentrate on the various strategies
      currently available for gene repair. The potential benefits of correction versus
      augmentation will be addressed and possible future developments outlined.

PMID- 11525558
TI  - Molecular approaches to therapy for Duchenne and limb-girdle muscular dystrophy.
AB  - The muscular dystrophies are a heterogeneous group of heritable disorders in
      which progressive muscle degeneration leads to regional or generalized weakness.
      Recent advances in molecular genetics, cell biology and vector discovery have
      improved the outlook for therapeutic intervention. This review focuses on novel
      approaches to the study of disease pathogenesis and refinements in gene- and cell
      based strategies for protein restoration in Duchenne and limb-girdle muscular
      dystrophy, and concludes with a brief discussion of priorities for future
      clinical investigation.

PMID- 11525557
TI  - Gene therapy for central nervous system repair.
AB  - The amelioration of the sequelae of CNS injury by gene therapy requires three
      post-injury events to be addressed: scarring, neuron death and axon regeneration.
      Administering anti-apoptotic, and axon growth promoting genes to neurons is
      inefficient, using nonviral vectors, because access to the transcriptional
      machinery is restricted by an intact nuclear membrane in G0 cells. Viral vectors
      have better transfection rates but a higher incidence of deleterious effects than
      non-viral vectors. Discrete targeted transfection of astrocytes, for example,
      about the wound with antifibrotic genes is essential to control scarring and for
      the inhibition of axon growth locally by gene products without transfecting
      neighboring and distant cells. Either rational or forced evolutionary design of
      vectors will ultimately achieve efficient safe gene transduction. Recombinant
      protein treatments for CNS repair have proved disappointing, probably because
      axotomized neurons are difficult to access in multiple disparate sites in the CNS
      after penetrant injury. Gene therapy has the potential to overcome these
      difficulties since sustained antiscarring/neurotrophic regimes are achievable
      after a single delivery to the site of injury by uptake by local injury
      responsive cells in the wound, and by axon terminals. Subsequent retrograde
      axonal transport delivers the therapeutic genes to all axotomized neurons
      throughout the CNS.

PMID- 11525559
TI  - Gene therapy strategies for X-linked adrenoleukodystrophy.
AB  - X-linked adrenoleukodystrophy (ALD) is the most frequently seen genetic disorder
      involving the myelin of the central nervous system. The cerebral form affects
      mainly boys between five to 12 years, leading to vegetative state or death within
      two to four years. The adult form affects the spinal cord, leading to severe
      paraplegia often complicated by cerebral demyelination. The ALD gene encodes an
      ATP-binding cassette transporter involved in the transport of very long chain
      fatty acids into peroxysomes. Specific subpopulations of oligodendrocytes and
      microglia are particularly affected by the ALD gene mutation and thus should be
      the target cells of gene therapy approaches. Two different and potentially
      complementary therapeutic strategies are currently evaluated. The first approach
      aims at replacing the endogenous brain microglia from patients by
      autotransplantation of genetically corrected hematopoietic stem cells using a
      lentiviral vector. The second approach aims at targeting directly the ALD gene
      into brain glial cells using stereotactic injections of viral vectors.

PMID- 11525560
TI  - Gene therapy for rheumatoid arthritis.
AB  - Gene therapy was initially conceived of as a means of replacing defective genes
      in monogenic disorders such as cystic fibrosis or hemophilia, but has rapidly
      progressed into areas of medicine that involve a wide range of diseases including
      cancer, neurodegenerative disorders and autoimmunity. Elucidation of some of the
      cellular and molecular mechanisms implicated in the pathogenesis of joint
      inflammation and cartilage and bone destruction in inflammatory joint diseases
      such as rheumatoid arthritis (RA) have revealed novel targets for gene therapy.
      Strategies include the inhibition of pro-inflammatory cytokines, blockade of
      cartilage-degrading enzymes, inhibition of synovial cell activation or apoptosis
      of synovial cells, and manipulation of the Th1-Th2 cytokine balance. Both viral
      and non-viral gene transfer vector systems have been used to deliver therapeutic
      genes systemically or directly to arthritic joints by ex vivo as well as in vivo
      administration. Animal models of RA have been essential not only for better
      understanding the mechanisms of RA but also in serving as basic experimental
      tools to evaluate candidate gene products with anti-arthritic properties and
      develop therapeutic strategies.

PMID- 11525561
TI  - Gene delivery of vaccines for infectious disease.
AB  - Genetic immunization is the process of delivering and expressing a gene (or
      therapeutic nucleic acid) encoding a pathogen-derived antigen into target host
      cells to elicit a protective humoral or cell-mediated immune response. Gene
      delivery methods to achieve this goal have expanded rapidly, and currently employ
      a variety of oligonucleotides, synthetic polypeptides, recombinant vectors and
      even edible plants, all of which have been shown to be capable of inducing
      protective immunity in experimental animal models. This review highlights recent
      progress in several gene delivery systems (both non-viral and viral methods)
      using novel in vivo approaches to engender effective host immune responses
      against the introduced antigen.

PMID- 11525562
TI  - Recent progress in gene therapy for cystic fibrosis.
AB  - Cystic fibrosis (CF) is a monogenic disorder and is therefore a good candidate
      for gene therapy. Initial clinical trials provided proof-of-principle for gene
      transfer to the airways, but efficiency was low and likely to be insufficient for
      clinical benefit. Here, we review the progress in CF gene therapy over the last
      12 months, including recent advances in viral and non-viral gene transfer agents
      and novel strategies, such as RNA repair and stem cell gene therapy.

PMID- 11525563
TI  - Gene therapy in transplantation.
AB  - In transplantation, gene therapy strategies to prolong graft survival involve
      gene transfer and expression of immunomodulatory or graft-protecting molecules.
      The local production of immunosuppressive molecules has the potential to reduce
      their systemic side effects, and to increase their bioavailability and hence
      their therapeutic efficiency. Ex vivo gene transfer enables manipulation prior to
      engraftment. Vectors have now been developed that can optimally transfer the
      relevant genes to various cells, tissues and organs. The elimination of
      genetically modified cells can even be time-controlled by prodrug administration
      in suicide gene therapy systems. Gene transfer to stem cells may eventually lead
      to accelerated tissue repair and regeneration. In addition, xenotransplantation
      and organ cloning techniques have the potential to resolve the current shortage
      of donor organs.

PMID- 11525564
TI  - Gene therapy for lysosomal storage disorders.
AB  - Deficiencies in one or several of the numerous degradative enzymes that reside in
      the lysosome often result in one of many clinically severe diseases, almost all
      of which have no currently available therapy. Although bone marrow
      transplantation, enzyme replacement and substrate inhibition therapies are being
      considered, gene therapy represents an increasingly attractive approach,
      particularly for those lysosomal storage diseases with neurological
      manifestations. This review summarizes the most recent advances in developing
      gene therapies for this large and heterogeneous group of disorders.

PMID- 11525565
TI  - Technology evaluation: CEA-TRICOM, Therion Biologics Corp.
AB  - Therion Biologics, the NCI and Aventis Pasteur are investigating CEA-TRICOM, a
      recombinant, pox virus-based vaccine that incorporates a triple dose of
      costimulatory molecules as well as the carcinoembryonic antigen (CEA) tumor
      antigen, for the potential treatment of colorectal cancer. CEA-TRICOM is designed
      to stimulate and strengthen the body's immune system to kill colorectal cancer
      cells. CEA-TRICOM is administered in a priming and boosting protocol using two
      unique pox virus vectors, rV-CEA-TRICOM (recombinant vaccinia vector) and rF-CEA
      TRICOM (recombinant fowlpox vector). The TRICOM component of both rV-CEA-TRICOM
      and rF-CEA-TRICOM comprises three costimulatory molecule transgenes (B7-1, ICAM-1
      and LFA-3) [414643], [414645], known to elicit strong cellular immune responses
      necessary for complete tumor destruction. In preclinical studies conducted by the
      NCI and Therion, researchers have demonstrated that this combination of three
      costimulatory molecules dramatically boosts the immune response to eradicate
      cancer in murine models [399610], [414631]. In February 2001, Therion Biologics
      and the NCI initiated a phase I trial of CEA-TRICOM [399610]. The phase I trial
      of CEA-TRICOM is designed to demonstrate proof-of-principle for using multiple
      costimulatory molecules in conjunction with a tumor antigen to improve the
      strength of cellular immune responses. It is a multistage, dose-escalation study
      that will assess the safety and immunologic effects of CEA-TRICOM in up to 42
      patients who have advanced metastatic colorectal cancer. Subjects will receive rF
      CEA-TRICOM alone, rV-CEA-TRICOM followed by booster vaccinations with rF-CEA
      TRICOM or rV-CEA-TRICOM followed by rF-CEA-TRICOM and GM-CSF adjuvant. The
      primary measure of immune response will be the level of CEA-specific T-cells
      stimulated by vaccination, with levels of CEA-expressing tumor cells in the blood
      used as a potential secondary measure of treatment effect [399610].

PMID- 11525566
TI  - Technology evaluation: HspE7, StressGen Biotechnologies Corp.
AB  - StressGen is developing HspE7 (SGN-00101) as a potential therapy for human
      papillomavirus (HPV)-associated conditions. It is a recombinant fusion protein
      comprising the HPV E7 antigen and the heat shock protein, hsp65, from
      Mycobacterium bovis. By November 2000, it was in phase III trials for HPV-related
      anal dysplasia [405228]. Under an aggrement formed in November 1999, the US
      National Cancer Institute (NCI) is carrying out clinical trials with StressGen in
      diseases caused by HPV [347155].

PMID- 11525567
TI  - Technology evaluation: IMC-1C11, ImClone Systems.
AB  - ImClone is developing IMC-IC11, an anti-angiogenesis chimeric monoclonal antibody
      specific vascular endothelial growth factor receptor 2 (VEGFR-2, also known Flk-1
      in mice), for the potential treatment of cancer [156625]; it in phase I trials
      for the treatment of colorectal carcinoma [379143]. The related antibody DC-101
      provided proof-of-principle that an anti-VEGF receptor antibody could strongly
      inhibit tumor growth and even cause tumor regression with the glioblastoma tumor
      cell line, GBM18 [388236]. In May 1998, the company was granted US-05747651 by
      the USPTO, covering antibodies against the extracellular portion of the FLK-1/KDR
      receptor [284054].

PMID- 11525568
TI  - Skill mix in clinical care.

PMID- 11525569
TI  - The control and regulation of scientific and medical research.

PMID- 11525570
TI  - To err is human: learning from mistakes.

PMID- 11525571
TI  - Acute renal failure.

PMID- 11525572
TI  - A practical approach to the diagnosis of venothromboembolism.

PMID- 11525573
TI  - Management of alcoholic hepatitis.

PMID- 11525574
TI  - Acute jaundice.

PMID- 11525575
TI  - Respiratory failure: two forgotten concepts.

PMID- 11525576
TI  - Infections in HIV disease.

PMID- 11525577
TI  - The changing role of the hospital in Europe: causes and consequences.
AB  - The United Kingdom, faced with a legacy of long-term under investment, has
      embarked on a major programme of hospital development. This raises many
      questions. What factors influence the work of the hospital? How can hospitals
      continue to adapt to changing circumstances? This paper draws on a recent study
      of the role of the hospital in Europe. It identifies major gaps in information
      about what hospitals do and how they are changing. International comparisons are
      especially difficult because of differences in definitions. The challenges that
      hospitals face can be categorised under three broad headings: the health needs of
      the population; opportunities and constraints they face in providing care; and
      the consequences of wider societal and economic factors that shape their
      environment. Health needs reflect the composition of the population (births,
      ageing, and migration), changes in risk factors, and changes in public
      expectations. Hospitals gain opportunities, but also face constraints as a result
      of changes in the workforce on which they draw and the technology that is
      available to them. They must also work within the constraints imposed by wider
      societal developments, such as the economy. Hospitals must also take account of
      their role as centres of teaching and research, as well as their responsibilities
      to the local community. Hospitals across Europe have changed considerably in the
      1990s, with more people being admitted but staying for shorter periods. With the
      additional demands created by growing rates of day care and outpatients,
      hospitals are currently much busier places than in the past. There have also been
      considerable reconfigurations of hospitals in many countries. Some have been more
      successful in implementing change than others. Successful change is more likely
      where a whole system approach to health care is taken. Granting managerial
      autonomy to individual hospitals makes change less likely. Planning approaches
      are more successful than market-based ones. Change often requires construction of
      new facilities. The increasingly rapid pace of change in health care means that
      hospitals will have to adapt much more quickly than in the past. This will
      require a long-term programme of sustained and stable investment.

PMID- 11525578
TI  - Research for an ageing society.
AB  - This article outlines the research agenda of the Economic and Social Research
      Council's Growing Older Programme. The Programme focuses on extending quality
      life and is composed of six sub-themes: defining and measuring quality of life;
      inequalities in quality of life; technology and the built environment; healthy
      and productive ageing; family and support networks; and participation and
      activity in later life. The Programme aims not only to produce high quality
      research on the factors determining quality in old age and how it can be extended
      but, also, to contribute constructively to policy and practice. The article also
      introduces the new UK National Collaboration in Ageing Research which brings
      together four of the research councils to raise the profile of research on ageing
      and to develop a multidisciplinary approach.

PMID- 11525579
TI  - Going Dutch? How to make clinical guidelines work: an innovative report from
      Holland.
AB  - This article describes the findings of a recent Dutch enquiry on the translation
      of modern medical evidence and research into good clinical practice. There is a
      huge current increase in 'clinical guidelines' for many diseases, but even when
      reasonably evidence-based, there is little evidence that they positively affect
      clinical practice and patient care to any great extent. Educational and
      management issues are as important as the quality of the clinical advice. Patient
      acceptance factors also need to be considered.

PMID- 11525580
TI  - Patient at risk!
AB  - Recent Department of Health-led reviews have recommended wide-ranging changes in
      the provision of critical care which will affect most physicians. Critically ill
      patients on general wards are too often missed, and intervention is often too
      late. Early warning scoring systems can improve outcome by detecting critical
      illness earlier and by acting as triage tools. The re-classification of care,
      levels 0-3, means that physicians and intensivists will increasingly work
      together to provide the level of care required for our sickest patients.

PMID- 11525582
TI  - Training in general (internal) medicine alone.
AB  - A freestanding training programme for general (internal) medicine (G(I)M) alone
      was established in the Oxford deanery four years ago. The programme was designed
      to provide three years' training post-MRCP for specialist registrars, selected in
      open competition, and covers all aspects of acute medical care including four
      months in intensive care. The first four to complete training have achieved
      consultant level appointments. The programme also attracted a number of trainees
      who wished to obtain appropriate qualifications in high dependency and critical
      care medicine. The programme offers the opportunity to create specialists
      properly trained in G(I)M who will be able to continue to provide an important
      service as specialists or practising as consultants in G(I)M alone.

PMID- 11525581
TI  - Management of acute myeloid leukaemia. A regional audit in the south and west of
      the United Kingdom.
AB  - In a retrospective audit data were collected on all 231 patients from 26
      hospitals diagnosed with AML in the south and west region of the UK in 1996.
      Their median age at diagnosis was 67 years. Sixty one percent (142/231) of
      patients were treated with chemotherapy; most of the rest received blood product
      support only; and 7% (15) had no treatment at all. Sixty eight percent of
      patients aged under 60 years were treated in a clinical trial compared with 24%
      of patients over 60. The major reasons given for not entering patients in a trial
      were ineligibility in the younger cohort and poor performance status in the older
      group. Twenty elderly patients (12.5%) refused to be entered in a trial. In an
      unselected cohort of patients with AML the accrual into clinical trials is
      impressively high for patients under 60 years. However, this is a disease of the
      elderly and comparable enrolment is not seen with elderly patients despite being
      managed by the same haematologists. If the percentage of patients entered into
      trials is to be defined as a quality standard, then it is important for those
      trials to be relevant to the population being treated.

PMID- 11525583
TI  - The consultation in art. Marriage a La Mode: The Inspection (1743) William
      Hogarth.

PMID- 11525584
TI  - Letters from S M Burroughs: the birth of a worldwide pharmaceutical enterprise.
AB  - Letters from Silas Burroughs to his junior partner Henry Wellcome and other
      business associates have recently come to light Written during his travels (1880
      1882) soon after the establishment of their pharmaceutical company, the letters
      show how this energetic, resourceful and imaginative salesman developed and
      expanded the business overseas and tackled the problems of preservation,
      packaging and marketing of medicines in tropical countries.

PMID- 11525585
TI  - The organ retention furore.

PMID- 11525586
TI  - Ethical approval for health research.

PMID- 11525588
TI  - Medical admissions can be made easier, quicker and better by the use of a pre
      printed Medical Admission Proforma.

PMID- 11525587
TI  - Capillary blood gas analysis for long term oxygen therapy assessment.

PMID- 11525589
TI  - Balancing the books.

PMID- 11525590
TI  - Serum micronutrients and cervical dysplasia in Southwestern American Indian
      women.
AB  - We carried out a clinic-based case-control study to assess serum micronutrients
      as risk factors for cervical dysplasia among Southwestern American Indian women,
      a group with high rates of cervical preinvasive lesions. Cases were American
      Indian women with biopsy-proven cervical intraepithelial neoplasia (CIN I or CIN
      II/III). Controls were from the same Indian Health Service clinics with normal
      cervical epithelium. We interviewed women about histories of sexually transmitted
      diseases, sexual behavior, diet, hygienic practices, cigarette smoking, and
      reproductive factors. Laboratory assays included serum for retinol (vitamin A),
      ascorbic acid (vitamin C), alpha-tocopherol (vitamin E), and red blood cell
      folate levels, DNA for human papillomavirus (HPV) typing, and tests for other
      sexually transmitted diseases. The strongest risks for cervical dysplasia were
      associated with cervical HPV infection [odds ratio (OR) = 3.2, 95% confidence
      interval (CI) = 2.2-4.6 and OR = 7.9, 95% CI = 4.8-13.1 for CIN I and CIN II/III,
      respectively]. With adjustments made for HPV infection and other relevant
      confounders, subjects in the lowest serum retinol quartile were at increased risk
      of CIN I compared with women in the highest quartile (OR = 2.3, 95% CI = 1.3
      4.1). The data suggest that low serum alpha-tocopherol was associated with CIN
      I/III, although the adjusted OR was not statistically significant (OR = 2.0, 95%
      CI = 0.9-4.8). Low serum ascorbic acid and red blood cell folate were not
      associated with cervical dysplasia.

PMID- 11525591
TI  - Inverse association between dietary and serum conjugated linoleic acid and risk
      of breast cancer in postmenopausal women.
AB  - Conjugated linoleic acid (CLA) is anticarcinogenic in experimental animal
      studies. We studied dietary and serum CLA in Finnish patients with breast cancer
      in 1992-1995. Participants were consecutive women with breast cancer (68
      premenopausal and 127 postmenopausal) and population-based control women (75
      premenopausal and 133 postmenopausal), matched for age and area of residence.
      Diet was assessed by a validated food frequency questionnaire and the fatty acid
      composition of serum by gas-liquid chromatography. In postmenopausal women,
      dietary CLA, serum CLA, myristic acid, and trans-vaccenic acid were significantly
      lower in cases than in controls. The odds ratio for breast cancer in the highest
      quintile vs. the lowest was 0.4 [95% confidence interval (CI) = 0.2-0.9]for CLA,
      0.3 (95% CI = 0.1-0.7) for myristic acid, and 0.3 (95% CI = 0.1-0.7) for trans
      vaccenic acid in serum. The odds ratios remained similar after adjustment for
      known risk factors of breast cancer. A diet composed of CLA-rich foods,
      particularly cheese, may protect against breast cancer in postmenopausal women,
      but it is impossible to assess the independent effects of CLA in this study. The
      findings may be of relevance for food production, inasmuch as it is possible to
      increase CLA and its precursor trans-vaccenic acid in foods by modifying the
      feeding of ruminants.

PMID- 11525592
TI  - Changes in sex hormone-binding globulin, insulin, and serum lipids in
      postmenopausal women on a low-fat, high-fiber diet combined with exercise.
AB  - Dietary factors including fat and fiber have been reported to play a role in the
      development of breast cancer, possibly mediated by changes in estradiol. Diet and
      exercise have been shown to affect levels of sex hormone-binding globulin (SHBG),
      which in turn regulate the bioavailability of estradiol. Diet and exercise also
      affect insulin levels, which play a role in the synthesis of SHBG, and the
      hormone itself is a potent mitogen for many cancer cell lines. This study was
      designed to measure the effects of a low-fat, high-fiber diet, combined with
      regular aerobic exercise, on the levels of SHBG, insulin, and serum lipids in
      postmenopausal women with or without hormone replacement therapy (HRT). Two
      groups of postmenopausal women, 11 on HRT and 11 not on HRT, underwent a low-fat
      (1O% fat calories), high-fiber (65-70 g/day) diet-and-exercise intervention for
      three weeks. Serum SHBG, insulin, and lipids were measured before and after the
      regimen. After the intervention, SHBG levels were significantly increased for the
      women on HRT (44.5 +/- 3.4 vs. 62 +/- 6.4 nmol/l) and the women not on HRT (32.1
      +/- 4.6 vs. 45.5 +/- 6.1 nmol/l, both changes p < 0.01). Also after the
      intervention, insulin levels were significantly reduced for the women on HRT (196
      +/- 44.4 vs. 119.8 +/- 28.7 pmol/l) and the women not on HRT (144.2 +/- 17.9 vs.
      115.5 +/- 20.8 pmol/l, both changes p < 0.01). Body mass index and total
      cholesterol were significantly reduced for both groups of women (all changes p <
      0.01). Although the exact mechanism for the change in SHBG is not known, the
      increases in SHBG and reductions in insulin as a result of this lifestyle
      intervention should reduce the risk for breast cancer in postmenopausal women.

PMID- 11525593
TI  - Relationships between types of fat consumed and serum estrogen and androgen
      concentrations in Japanese men.
AB  - The relationships between types of fat consumed and serum concentrations of
      estrone, estradiol, total and free testosterone, dihydrotestosterone, and sex
      hormone-binding globulin were examined in 69 Japanese men aged 43-88 years. Diet
      was assessed by a semiquantitative food frequency questionnaire. Intake of
      saturated, monounsaturated, and polyunsaturated fats was inversely correlated
      with serum total testosterone after controlling for age, total energy, body mass
      index, alcohol intake, and smoking status, but the correlation was statistically
      significant only for polyunsaturated fat (r = -0.29, p = 0.02). Intakes of
      eicosapentanoic and docosahexaenoic acids, n-3 fatty acids from fish, were
      significantly inversely correlated with total testosterone (r = -0.25, p = 0.04
      and r = -0.32, p = 0.01, respectively). Serum estrone, estradiol, and free
      testosterone were not significantly correlated with any type of fat studied. The
      correlations of total testosterone with n-3 fatty acids from fish remained
      significant after additional adjustment for the other categories of fat (r = 
      0.27, p = 0. 03 for eicosapentanoic acid and r = -0.32, p = 0.01 for
      docosahexaenoic acid), while the correlations with saturated and monounsaturated
      fats became nearly null after the adjustment.

PMID- 11525594
TI  - Disposition of glucosinolates and sulforaphane in humans after ingestion of
      steamed and fresh broccoli.
AB  - The cancer-chemopreventive effects of broccoli may be attributed, in part, to
      isothiocyanates (ITCs), hydrolysis products of glucosinolates. Glucosinolates are
      hydrolyzed to their respective ITCs by the enzyme myrosinase, which is
      inactivated by heat. In this study, the metabolic fate of glucosinolates after
      ingestion of steamed and fresh broccoli was compared in 12 male subjects in a
      crossover design. During each 48-hour baseline period, no foods containing
      glucosinolates or ITCs were allowed. The subjects then consumed 200 g of fresh or
      steamed broccoli; all other dietary sources of ITCs were excluded. Blood and
      urine samples were collected during the 24-hour period after broccoli
      consumption. Total ITC equivalents in broccoli and total ITC equivalents in
      plasma and urine were assayed by high-performance liquid chromatography as the
      cyclocondensation product of 1,2-benzenedithiol. The content of ITCs in fresh and
      steamed broccoli after myrosinase treatment was found to be virtually identical
      (1.1 vs. 1.0 micromol/g wet wt). The average 24-hour urinary excretion of ITC
      equivalents amounted to 32.3 +/- 12.7% and 10.2 +/- 5.9% of the amounts ingested
      for fresh and steamed broccoli, respectively. Approximately 40% of total ITC
      equivalents in urine, 25.8 +/- 13.9 and 6.9 +/- 2.5 micromol for fresh and
      steamed broccoli, respectively, occurred as the N-acetyl-L-cysteine conjugate of
      sulforaphane (SFN-NAC). Total ITC metabolites in plasma peaked between 0 and 8
      hours, whereas urinary excretion of total ITC equivalents and SFN-NAC occurred
      primarily between 2 and 12 hours. Results of this study indicate that the
      bioavailability of ITCs from fresh broccoli is approximately three times greater
      than that from cooked broccoli, in which myrosinase is inactivated. Considering
      the cancer-chemopreventive potential of ITCs, cooking broccoli may markedly
      reduce its beneficial effects on health.

PMID- 11525595
TI  - Associations of plasma aflatoxin B1-albumin adduct level with plasma selenium
      level and genetic polymorphisms of glutathione S-transferase M1 and T1.
AB  - Mortality from hepatocellular carcinoma (HCC) is extraordinarily high in Matzu,
      an island off the coast of Southeastern China. To investigate factors associated
      with plasma aflatoxin B1 (AFB1)-albumin adduct level, we studied 304 healthy
      adult residents from Matzu. AFB1-albumin adducts were determined by competitive
      enzyme-linked immunosorbent assay, hepatitis B surface antigen status by enzyme
      immunoassay, genotypes of glutathione S-transferase (GST) M1 and T1 by polymerase
      chain reaction, plasma selenium by atomic absorption spectrometry, and plasma
      retinol, alpha-tocopherol, alpha-carotene, and beta-carotene levels by high
      performance liquid chromatography. Men had higher AFB1-albumin adduct levels than
      women. GSTM1-nonnull and GSTT1-null genotypes and low plasma selenium level were
      significantly associated with an increased level of AFB1-albumin adducts among
      men, whereas age was significantly correlated with adduct level among women. High
      intake of fermented beans was associated with an increased adduct level among men
      and women. The inverse associations between plasma selenium level and AFB1
      albumin adducts were statistically significant among those with null genotypes of
      GSTM1 and GSTT1, but not among the nonnull genotypes. This study provides insight
      into the dietary and genetic factors influencing AFB1-albumin adduct formation in
      an isolated population with high liver cancer mortality.

PMID- 11525596
TI  - Reflux-inducing dietary factors and risk of adenocarcinoma of the esophagus and
      gastric cardia.
AB  - Gastroesophageal reflux (GER) is the strongest known risk factor for esophageal
      adenocarcinoma. For long-term sufferers with severe symptoms, the excess risk may
      exceed 40-fold. GER has also been shown to increase the risk of cancers of the
      gastric cardia more than fourfold. Several foods, including dietary fat,
      chocolate, mints, coffee, onions, citrus fruit, and tomatoes, have been
      associated with temporary symptoms of reflux, most likely through a relaxation of
      the lower esophageal sphincter (LES). Our aim was to determine whether these
      foods are associated with risk of adenocarcinoma of the esophagus or gastric
      cardia. We studied intakes of LES-relaxing foods and other dietary habits
      potentially associated with reflux in a nationwide population-based case-control
      study in Sweden, with 185 and 258 cases of esophageal adenocarcinoma and gastric
      cardia adenocarcinoma, respectively, and 815 controls. We found no association
      between LES-relaxing foods and symptoms of chronic reflux, although this might be
      due to avoidance of these foods among sufferers. In addition, we found no
      association between dietary factors known to cause LES relaxation and the risk of
      adenocarcinoma of the esophagus or gastric cardia. Our findings indicate that
      dietary factors associated with LES relaxation and transient GER (but perhaps not
      severe chronic reflux) are not associated with any important risk of esophageal
      malignancy.

PMID- 11525597
TI  - Orally administered lactoferrin exerts an antimetastatic effect and enhances
      production of IL-18 in the intestinal epithelium.
AB  - The effects of oral administration of bovine lactoferrin (bLF) and its
      hydrolysate on the lung colonization by colon 26 carcinoma were investigated. At
      doses of 100 or 300 mg/kg/day for seven successive days, bLFs demonstrated a
      significant inhibitory effect on experimental metastasis, which indicated
      effectiveness before and after tumor implantation. Oral administration of bLFs
      augmented CD4+, CD8+, and asialoGM1+ cells in the spleen and peripheral blood.
      Their cytotoxic activities against Yac-1 and colon 26 carcinoma were enhanced by
      bLF. In the small intestinal epithelium, CD4+ and CD8+ cells were markedly
      increased, and, simultaneously, enhanced production of interleukin-18 (IL-18) was
      confirmed in the intestinal epithelial cells. In this model, intravenous
      injection of murine IL-18 showed significant inhibition of the lung colonization
      by colon 26 carcinoma. These results suggested that inhibition of experimental
      metastasis by oral administration of bLF and pepsin hydrolysate of bLF might be
      due to enhanced cellular immunity, presumably mediated by enhanced IL-18
      production in the intestinal epithelium.

PMID- 11525598
TI  - Enchancing effect of patented whey protein isolate (Immunocal) on cytotoxicity of
      an anticancer drug.
AB  - To determine the enhancing effect of a whey protein isolate on the cytotoxicity
      of a potential anticancer drug, baicalein, the human hepatoma cell line Hep G2
      was assigned to grow in different media for four days, and cell growth and
      apoptosis were investigated. The control group was grown in normal medium; the
      other three groups were grown in whey protein isolate (Immunocal) medium,
      baicalein medium, and a combination of Immunocal and baicalein. As indicated by 3
      (4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, survival rate
      was significantly lower in cells grown in baicalein + Immunocal than in cells
      grown in baicalein alone. In contrast, there was no significant difference in
      survival rate of the cells grown in Immunocal. In the investigation of apoptosis,
      cells grown in baicalein + Immunocal showed a higher phosphatidylserine exposure,
      lower mitochondrial transmembrane potential, and nearly 13 times more cells
      undergoing apoptosis than cells grown in baicalein alone. We also demonstrated
      that Immunocal reduced glutathione (GSH) in Hep G2 cells by 20-40% and regulated
      the elevation of GSH, which was in response to baicalein. In conclusion,
      Immunocal seemed to enhance the cytotoxicity of baicalein by inducing more
      apoptosis; this increase in apoptotic cells may be associated with the depletion
      of GSH in Hep G2 cells. This is the first study to demonstrate, in vitro, that
      Immunocal may function as an adjuvant in cancer treatments.

PMID- 11525599
TI  - Effect of dietary soy isoflavone aglycones on the urinary 16alpha-to-2
      hydroxyestrone ratio in C3H/HeJ mice.
AB  - Estradiol is metabolized through two mutually exclusive pathways. 2
      Hydroxyestrone (2-OHE,) is antiestrogenic, while 16alpha-hydroxyestrone (16alpha
      OHE1) is a potent estrogen. It is suggested that a high urinary 16alpha-OHE1-to-2
      OHE1 rato is a biomarker of increased mammary tumor risk. Mice were fed one of
      the test diets for 21 days. Indole-3-carbinol (2,500 mg/kg diet) increased the
      cytochrome P-450 content of hepatic microsomes and liver weight and reduced the
      urinary 16alpha-OHE1-to-2-OHE1 ratio in comparison with the respective value in
      the control mice. Fermented soy extract (100, 200, or 400 mg isoflavonoid/kg
      diet), genistein (200 mg/kg diet), and daidzein (200 mg/kg diet) each reduced the
      urinary 16alpha-OHE1-to-2-OHE1 ratio without increasing the cytochrome P-450
      content of hepatic microsomes or liver weight. The combination of genistein and
      daidzein (100 mg and 100 mg/kg diet) did not have a synergistic effect on the
      reduction in urinary 16alpha-OHE1-to-2-OHE1 ratio. These data suggest that the
      soy isoflavonoid aglycones genistein and daidzein and indole-3-carbinol each
      exert a cancer-preventive effect by shifting metabolism away from the production
      of genotoxic metabolites toward the production of inactive metabolites.

PMID- 11525600
TI  - Chemoprevention of aflatoxin B1-initiated and carbon tetrachloride-promoted
      hepatocarcinogenesis in the rat by green tea.
AB  - Chemoprevention of hepatocarcinogenesis by green tea (GT) has been examined in
      young male Fischer rats fed AIN-76A diet with aflatoxin B1 (AFB1) and CCl4 as the
      initiator and promoter, respectively. Animals were administered AFB1 (0.25 mg/kg
      body wt ip) twice a week for 2 weeks, and 2 weeks later, CCl4 was injected (0.8
      ml/kg body wt ip) once per week for 11 weeks. Rats given 0.5% GT in their
      drinking water before and during initiation (0-4 wk) or during promotion (6-16
      wk) or throughout the experimental period were sacrificed 24 hours after the last
      dose of CCl4. Bromodeoxyuridine incorporation as a measure of cell proliferation
      and glutathione S-transferase placentalform- and gamma-glutamyl transpeptidase
      positive hepatic foci were analyzed by histochemical methods. Feeding of GT
      during initiation or promotion inhibited the number of glutathione S-transferase
      placental form- and gamma-glutamyl transpeptidase-positive hepatic foci by 30-40%
      and the area and volume by 50%. GT treatment throughout the period inhibited the
      number of both types of hepatic foci by 60% and the area and volume by 75-80%.
      Cell proliferation was inhibited 35% by GT given during promotion, whereas
      inhibition was 65% when GT was given during initiation or throughout the period.
      These results indicate that GT feeding inhibits initiation and promotion steps of
      AFB1 hepatocarcinogenesis and that the inhibition of cell proliferation is
      responsible for the inhibition of promotion.

PMID- 11525601
TI  - Effects of phytoestrogens on growth and DNA integrity in human prostate tumor
      cell lines: PC-3 and LNCaP.
AB  - Prostate cancer is one of the most common male cancers in Western countries, yet
      the incidence of this fatal disease remains low in Asian populations.
      Environmental factors such as diet play an important role in hormone-dependent
      cancer etiology, and a high phytoestrogen intake may be one factor contributing
      to the low prostate cancer mortality in Eastern populations. In this study, we
      investigated the effects of the phytoestrogens genistein, daidzein, coumestrol,
      and equol on cell growth and DNA damage (strand breakage) in two human prostate
      tumor cell lines: androgen receptor-positive LNCaP and androgen receptor-negative
      PC-3. Each compound caused growth inhibition at physiologically relevant
      concentrations (<10 microM). Genistein induced DNA damage in both cell lines at
      <10 microM. Daidzein inhibited cell growth at 10-100 microM yet had no effect on
      DNA damage at up to 500 microM. Thus, despite their structural similarities,
      different phytoestrogens inhibit prostate tumor cell growth by independent
      mechanisms.

PMID- 11525602
TI  - Estrogenic and antiestrogenic activities of flavonoid phytochemicals through
      estrogen receptor binding-dependent and -independent mechanisms.
AB  - Members of the flavonoid class of phytochemicals have previously been
      demonstrated to possess estrogenic activity in a number of hormonally responsive
      systems. We have performed the present study to characterize the estrogenic and
      antiestrogenic activity of flavonoids in the estrogen receptor (ER)-positive MCF
      7 human breast cancer cell line. Using an ER-dependent reporter gene assay and an
      ER competition binding assay, we have identified phytochemicals possessing
      estrogenic and antiestrogenic activities, which appeared to correlate directly
      with their capacity to displace [3H]estradiol from ER. Several flavonoids,
      including kaempferide, apigenin, and flavone, were distinct, in that their
      antiestrogenic activity did not appear to correlate with binding to ER, and
      therefore their suppression of estrogen-mediated gene transactivation and
      proliferation may occur independent of direct antagonism of the receptor. Further
      examination in HEK-293 cells transfected with ERalpha or ERbeta demonstrated
      potent antagonism with kaempferide and apigenin, while flavone was weakly
      antagonistic only toward ERP. These results suggest that the receptor binding
      independent antiestrogenic chemicals may function through alternate signaling
      pathways as indirect ER modulators in a receptor- and cell type-specific manner.
      We conclude that antiestrogenic activities of flavonoid phytochemicals may occur
      through ER binding-dependent and -independent mechanisms and that the binding
      independent antiestrogen activity of certain flavonoids is biologically
      significant in regulation of breast cancer cell proliferation.

PMID- 11525603
TI  - Effect of purified allicin, the major ingredient of freshly crushed garlic, on
      cancer cell proliferation.
AB  - The diverse health benefit effects of garlic include its anticancer activity.
      However, very little is known about such activity of isolated garlic compounds,
      among which allicin (the major ingredient of crushed garlic) has been the least
      studied. The aim of this work was to determine whether pure allicin exhibits the
      antiproliferative effect reported for garlic in in vitro models. Allicin, but not
      its precursor alliin, inhibited proliferation of human mammary (MCF-7),
      endometrial (Ishikawa), and colon (HT-29) cancer cells (50% inhibitory
      concentration = 10-25 microM). Two of three tested primary lines of human
      fibroblasts displayed a similar response to allicin (50% inhibitory concentration
      = 16-40 microM), whereas the third line was almost unaffected by this compound.
      The pure allicin and water extract of garlic powder with equivalent allicin
      concentrations displayed a similar potency, suggesting that allicin is
      responsible for the antiproliferative effect of the extract. The growth
      inhibition was accompanied by accumulation of cells in the G0/G1 and G2/M phases
      of the cell cycle (MCF-7 cells) and not by a significant increase in cell death.
      Allicin caused a transient drop in the intracellular glutathione (GSH) level, the
      magnitude and kinetics of which significantly varied depending on cell type. The
      extent of the decrease in GSH levels correlated well (r = 0.75) with the growth
      inhibitory activity of allicin. On the basis of these findings, we suggest that
      allicin plays a major role in the antiproliferative effect of water-soluble
      garlic preparations and that this effect may be attributed to the ability of
      allicin to transiently deplete the intracellular GSH level.

PMID- 11525604
TI  - Cell cycle arrest and differential gene expression in HT-29 cells exposed to an
      aqueous garlic extract.
AB  - Epidemiological data show an inverse correlation between garlic consumption and
      the risk for colon cancer. To examine this relationship, HT-29 human
      adenocarcinoma cells were cultured in the presence and absence of an aqueous
      garlic extract. Garlic treatment resulted in a fraction of cells detaching from
      the culture flasks. These cells remained viable. Flow cell cytometry showed that
      untreated cells exhibited a normal distribution among phases of the cell cycle,
      with 12% of cells at the G2/M boundary. Of the garlic-treated cells remaining
      attached to the flask, 27% were present at the G2/M boundary. Treated cells that
      detached from the flask were found almost exclusively (89%) at the G2/M boundary.
      RNA fingerprinting and microarray analysis showed that expression of the gene for
      menin was twice as high in control cells as in detached treated cells. In
      contrast, expression of genes for epidermal growth factor receptor and integrin
      alpha6 was nearly twice as high in detached treated cells as in control cells.
      These changes in gene expression were consistent with an arrest of the cell cycle
      at the G2/M boundary. Garlic's arrest of the cell cycle in human adenocarcinoma
      cells may explain in part its anticarcinogenic properties.

PMID- 11525605
TI  - Induction of apoptosis and cell cycle arrest in cancer cells by in vivo
      metabolites of teas.
AB  - The present study was conducted to determine in vivo possibilities of inducing
      apoptosis and cell cycle arrest in rat cancer cells by green, oolong, and black
      teas and also to further identify the mechanisms inhibiting cancer cell
      proliferation by the sera from tea-treated rats. The tea extracts from these
      three kinds of tea, the rat sera obtained after oral intubation of the tea
      extracts, and the tea polyphenolic compounds, (-)-epigallocatechin-3-gallate, (-)
      epigallocatechin, (-)-epicatechin-3-gallate, and the aflavins, were used in the
      related tests. The extracts, the sera from the treated rats, and the polyphenolic
      compounds significantly inhibited the proliferation of a rat hepatoma cell line
      (AH109A) and murine B16 melanoma cells but not normal rat mesothelial (M) cells.
      (-)-Epicatechin exhibited synergistic effects with (-)-epigallocatechin-3
      gallate, (-)-epicatechin-3-gallate, and theaflavins against AH109A cell
      proliferation. The fluorescence staining of the nuclei, electrophoresis detection
      of DNA fragmentation, and analysis of cell cycle indicated that the sera from the
      tea-treated rats, the tea extracts, and the related tea components resulted in
      loss of viability, apoptosis, and cell cycle arrest at the G1 phase in AH109A
      and/or B16 cells, but not in normal M cells. Our results suggest that induction
      of apoptosis and cell cycle arrest may be important mechanisms of in vivo
      proliferation inhibition of AH109A and other cancer cells by these teas.

PMID- 11525606
TI  - Stimulatory effect of arachidonic acid on T-47D human breast cancer cell growth
      is associated with enhancement of cyclin D1 mRNA expression.
AB  - Experimental and human studies have provided evidence that a high intake of n-6
      polyunsaturated fatty acids stimulates mammary carcinogenesis. Arachidonic acid,
      an n-6fatty acid consumed in the diet or derived from dietary linoleic acid, is
      thought to play a key role in enhancement of mammary tumor development. In this
      study, we investigated the effects of arachidonic acid on T-47D breast cancer
      cell growth, cell cycle progression, and the expression of cyclin D1 mRNA. Our
      data show that arachidonic acid stimulated the growth of T-47D cells with a
      twofold stimulation at 5 microg/ml. This effect was associated with an increase
      in the proportion of cells in the S phase of the cell cycle and preceded by
      stimulation of the expression of cyclin D1 mRNA, with maximal induction at 5
      microg/ml. Cyclin D1 mRNA levels were increased within two hours of treatment and
      were maximal at five hours. These results suggest that arachidonic acid may exert
      a stimulatory effect on breast cancer cell growth and that this effect possibly
      involves the induction of cyclin D1 gene expression leading to cell cycle
      progression.

PMID- 11525607
TI  - Pyridoxal supplementation reduces cell proliferation and DNA synthesis in
      estrogen-dependent and -independent mammary carcinoma cell lines.
AB  - In previous studies, decreased growth of tumor cells by vitamin B-6 treatment has
      been attributed to modulation of steroid hormone action. Therefore, the growth
      inhibiting properties of pyridoxal (PL) supplementation were studied in estrogen
      receptor-positive, MCF-7 and T-47D, and estrogen receptor-negative, BT-20, breast
      cancer cell lines. Cell counting and [3H]thymidine incorporation into DNA were
      used to assess growth, and analysis of pS2 expression was used to determine
      whether PL supplementation affected estrogen action. Treatment with 100 or 300 mM
      PL resulted in dose-dependent decreases in total cell numbers in the absence (26
      85% and 72-98%, respectively) and presence (38-42% and 88-98%, respectively) of
      estradiol in all cell lines studied compared with control cells cultured without
      PL supplementation. Similar decreases in DNA synthesis were observed in response
      to PL supplementation. Incorporation of [3H]thymidine into DNA of cells cultured
      with 100 or 300 microM PL was decreased by 30-90% and 96-99%, respectively, in
      the absence and by 32-40% and 82-99%, respectively, in the presence of estradiol.
      Northern analysis showed that expression of the estrogen-sensitive gene pS2 was
      not affected by either concentration of PL. These results indicate that PL
      supplementation regulates breast cancer cell growth in vitro via a mechanism that
      appears to be steroid independent.

PMID- 11525608
TI  - Baicalein, a novel apoptotic agent for hepatoma cell lines: a potential medicine
      for hepatoma.
AB  - This study has demonstrated that baicalein has anticancer effectiveness against
      human hepatoma cells. The dose response of baicalein in Hep G2 and Hep J2 cells
      indicates that baicalein decreased viability >90%. In comparison, baicalein had
      only minimal effects on the viability of control Chang liver cells. Flow
      cytometric analysis showed that baicalein inhibited the cell cycle of Hep G2
      cells in the S phase. In addition, baicalein treatment resulted in a decreased
      mitochondrial transmembrane potential and damaged the integrity of the cell
      membrane. The TdT-mediated dUTP-biotin nick end labeling assay results indicated
      that baicalein elicited a significant increase of DNA fragmentation in Hep G2
      cells after incubation for 48 hours. These results indicate that baicalein is an
      effective antihepatoma agent with minimal influence on noncancer cells. The
      effects of baicalein on Hep G2 cells include inhibition of the S phase of the
      cell cycle, dysfunction of mitochondria, and initiation of apoptosis.

PMID- 11525609
TI  - Micronutrient supplementation for patients with metastatic cancer.

PMID- 11525610
TI  - Guidelines for evaluation and treatment of gastroesophageal reflux in infants and
      children: recommendations of the North American Society for Pediatric
      Gastroenterology and Nutrition.
AB  - Gastroesophageal reflux (GER), defined as passage of gastric contents into the
      esophagus, and GER disease (GERD), defined as symptoms or complications of GER,
      are common pediatric problems encountered by both primary and specialty medical
      providers. Clinical manifestations of GERD in children include vomiting, poor
      weight gain, dysphagia, abdominal or substernal pain, esophagitis and respiratory
      disorders. The GER Guideline Committee of the North American Society for
      Pediatric Gastroenterology and Nutrition has formulated a clinical practice
      guideline for the management of pediatric GER. The GER Guideline Committee,
      consisting of a primary care pediatrician, two clinical epidemiologists (who also
      practice primary care pediatrics) and five pediatric gastroenterologists, based
      its recommendations on an integration of a comprehensive and systematic review of
      the medical literature combined with expert opinion. Consensus was achieved
      through Nominal Group Technique, a structured quantitative method. The Committee
      examined the value of diagnostic tests and treatment modalities commonly used for
      the management of GERD, and how those interventions can be applied to clinical
      situations in the infant and older child. The guideline provides recommendations
      for management by the primary care provider, including evaluation, initial
      treatment, follow-up management and indications for consultation by a specialist.
      The guideline also provides recommendations for management by the pediatric
      gastroenterologist. This document represents the official recommendations of the
      North American Society for Pediatric Gastroenterology and Nutrition on the
      evaluation and treatment of gastroesophageal reflux in infants and children. The
      American Academy of Pediatrics has also endorsed these recommendations. The
      recommendations are summarized in a synopsis within the article. This review and
      recommendations are a general guideline and are not intended as a substitute for
      clinical judgment or as a protocol for the management of all patients with this
      problem.

PMID- 11525611
TI  - Polyester and polycarbonate synthesis by in vitro enzyme catalysis.
AB  - Enzyme technology has significantly expanded in scope and impact over the past 10
      years to include organic transformations in non-traditional environments. This is
      in part due to an increased understanding and capability of using enzyme
      catalysis in a wide variety of organic solvents, at interfaces, and at high
      temperatures and pressures. This review focuses on a relatively new but rapidly
      expanding research activity where in vitro enzyme catalysis is used for the
      synthesis of non-natural polyesters and polycarbonates. The inclination to use of
      enzymes for polymer synthesis has been fueled by a desire to carry out these
      reactions in the absence of heavy metals, at lower temperatures, and with
      increased selectivity. Aspects of this work that include enzyme-catalyzed step
      growth condensation reactions, chain-growth ring-opening polymerizations, and
      corresponding transesterification of macromolecular substrates are discussed.

PMID- 11525612
TI  - The use of transgenic plants in the bioremediation of soils contaminated with
      trace elements.
AB  - The use of plants to clean-up soils contaminated with trace elements could
      provide a cheap and sustainable technology for bioremediation. Field trials
      suggested that the rate of contaminant removal using conventional plants and
      growth conditions is insufficient. The introduction of novel traits into high
      biomass plants in a transgenic approach is a promising strategy for the
      development of effective phytoremediation technologies. This has been exemplified
      by generating plants able to convert organic and ionic forms of mercury into the
      less toxic, volatile, elemental mercury, a trait that occurs naturally only in
      some bacteria and not at all in plants. The engineering of a phytoremediator
      plant requires the optimization of a number of processes, including trace element
      mobilization in the soil, uptake into the root, detoxification and allocation
      within the plant. A number of transgenic plants have been generated in an attempt
      to modify the tolerance, uptake or homeostasis of trace elements. The phenotypes
      of these plants provide important insights for the improvement of engineering
      strategies. A better understanding, both of micronutrient acquisition and
      homeostasis, and of the genetic, biochemical and physiological basis of metal
      hyperaccumulation in plants, will be of key importance for the success of
      phytoremediation.

PMID- 11525613
TI  - Bacterial cellulose production under oxygen-enriched air at different fructose
      concentrations in a 50-liter, internal-loop airlift reactor.
AB  - Bacterial cellulose (BC) production by Acetobacter xylinum subsp. sucrofermentans
      BPR2001 was carried out in a 50-1 internal-loop airlift reactor in air at an
      initial fructose concentration of 40 g/l. The BC production rate was 0.059 g/l
      per h. When oxygen-enriched air was supplied instead of air, the BC production
      rate increased to 0.093 g/l per h, and the BC yield was enhanced from 11% in air
      to 18%. When the initial fructose concentrations were varied from 30 to 70 g/l,
      the highest BC yield (35%) the highest production rate (0.22 g/l x per h), and
      the highest concentration of BC produced (10.4 g/l) were observed at 60-70 g/l
      fructose. From the carbon mass balance calculated at the final stage of
      cultivation, it was observed that enhanced BC production was reflected as a
      decrease in both CO2 evolution and the concentration of other unknown substances,
      suggesting the efficient utilization of energy for BC synthesis despite O2
      limitation.

PMID- 11525614
TI  - Efficient pyruvate production by a multi-vitamin auxotroph of Torulopsis
      glabrata: key role and optimization of vitamin levels.
AB  - A multi-vitamin auxotroph, Torulopsis glabrata strain WSH-IP303, which can use
      ammonium chloride as a sole nitrogen source for pyruvate production, was
      selected. To optimize pyruvate yield and productivity, a simple but useful,
      orthogonal design method, was used to investigate the relationship between
      thiamine, nicotinic acid, pyridoxine, biotin, and riboflavin. Thiamine was
      confirmed to be the most important factor affecting pyruvate production. When the
      concentration of thiamine was 0.01 mg/l or 0.015 mg/l, glucose consumption was
      improved by increasing the nicotinic acid concentration. When the concentrations
      of nicotinic acid, thiamine, pyridoxine, biotin, and riboflavin were 8.0, 0.015,
      0.4, 0.04, and 0.1 mg/l, respectively, pyruvate concentration and yield reached
      52 g/l and 0.52 g/g, respectively, in a 48-h flask culture. By employing a
      combination of the optimum vitamin concentrations, a batch culture was conducted
      in a 2.5-l fermentor with an initial glucose concentration of 112 g/l; and the
      pyruvate concentration reached 69 g/l after 56 h (yielding 0.62 g/g).

PMID- 11525615
TI  - Glycerol production by a novel osmotolerant yeast Candida glycerinogenes.
AB  - Candida glycerinogenes, an osmotolerant yeast isolated from a natural sample in
      an environment of high osmotic pressure, had a modest sugar-tolerance and an
      extremely high glycerol productivity. The optimum conditions for glycerol
      formation by C. glycerinogenes were a temperature of 29-33 degrees C and a pH of
      4-6. The optimum medium for glycerol production consisted of 230-250 g glucose/l,
      2 g urea/l and 5 ml corn steep liquor/l (55-65 mg phosphates/l); the pH was not
      adjusted. The highest yield of glycerol was 64.5% (w/w) based on consumed glucose
      from 240 g glucose/l, and the highest concentration of glycerol was 137 g/l from
      260 g glucose/l. These results were obtained by using a 30-l agitated fermentor
      under optimal fermentation conditions. In ten batch-fermentations carried out in
      a 50,000-l airlift fermentor, an average yield of glycerol of 50.67% (w/w) and an
      average glycerol concentration of 121.9 g/l were obtained from an average 240.6 g
      glucose/l.

PMID- 11525616
TI  - Effects of stress factors, bioregulators, and synthetic precursors on indole
      alkaloid production in compact callus clusters cultures of Catharanthus roseus.
AB  - Compact callus cluster (CCC) cultures established from Catharanthus roseus
      consist of cohesive callus aggregates displaying certain levels of cellular or
      tissue differentiation. CCC cultures synthesize about two-fold more indole
      alkaloids than normal dispersed-cell cultures. Our studies here show that
      additions of KCl, mannitol, and a variety of synthetic precursors and
      bioregulators to the CCC cultures markedly improved indole alkaloid production
      and release of these alkaloids into the medium. Treatment with 250 mM mannitol
      and 4 g/l KCl yielded 42.3 mg l(-1) and 33.6 mg l(-1)of ajmalicine, respectively;
      these amounts were about four-fold higher than the control. Succinic acid,
      tryptamine, and tryptophan feedings also significantly increased ajmalicine (41.5
      mg l(-1), 36.9 mg l(-1), and 31.8 mg l(-1), respectively) and catharanthine (21.1
      mg l(-1), 17.2 mg l(-1), and 18 mg l(-1), respectively) production by the CCC
      cultures, while geraniol feeding inhibited biomass and alkaloid accumulation. We
      also found that tetramethyl ammonium bromide could significantly improve
      ajmalicine production (49.3 mg l(-1)) and catharanthine production (18.3 mg l(
      1)) in C. roseus CCC cultures. The mechanisms responsible for these treatment
      effects are discussed herein.

PMID- 11525617
TI  - Enzymatic modification of kraft lignin through oxidative coupling with water
      soluble phenols.
AB  - The aromatic polymer lignin can be modified through promotion of oxidative
      coupling between phenolic groups on lignin and various phenols. The reaction is
      initiated by an oxidation of both components, e.g., by using the oxidoreductases
      laccase or peroxidase. Coupling between phenolic monomers and lignin has
      previously been studied by the use of radio-labeled phenols. In this study,
      incorporation of water-soluble phenols into kraft lignin, using laccase as
      catalyst, was investigated. Several phenols with carboxylic or sulfonic acid
      groups were used as markers for the incorporation. The modified lignin was
      isolated and the amount of phenol incorporated was characterized by means of
      titration, quantitative 1H-NMR, and quantitative 31P-NMR after modification with
      2-chloro-4,4,5,5-tetramethyl-1,2,3-dioxaphospholane. Only a few of the phenols
      studied were found to be incorporated into lignin. When the phenol guaiacol
      sulfonate was incorporated into kraft lignin, the lignin became water-soluble at
      pH 2.4 and a low ionic strength due to the introduction of sulfonic acid groups.
      The content of sulfonic acid groups in the product was 0.5-0.6 mmol/g lignin. A
      lower amount of 4-hydroxyphenylacetic acid was incorporated under similar
      conditions.

PMID- 11525618
TI  - Production of manganese peroxidase by pellet culture of the lignin-degrading
      basidiomycete, Pleurotus ostreatus.
AB  - Pleurotus ostreatus No. 42 produced the ligninolytic enzymes, manganese
      peroxidase (MnP) and laccase, in agitation culture in glucose/peptone/wheat-bran
      medium. Formation of mycelial pellets 1-2 mm in diameter was essential for the
      production of MnP; and the concentration of dissolved oxygen in the culture
      medium greatly influenced the production of MnP, a concentration over 5 ppm being
      necessary for MnP production. The maximal activity of MnP was obtained on days 7
      9 of culture, after the consumption of nutrient glucose. Introduction of oxygen
      from the start of the cultivation caused large pellet formation, which resulted
      in a low MnP activity level. P. ostreatus No. 42 produced two MnP isozymes in
      agitation culture. The major isozyme, F-2, was 36.4 kDa and had a pI of 3.95. The
      MnP characteristics, Km values, dependence on Mn2+ and optimum pH showed the
      similarity between this isozyme and MnP 3, which was produced under different
      culture conditions. Analysis of the N-terminal amino acid sequence indicated the
      close similarity of F-2 to MnP 3.

PMID- 11525619
TI  - Characterization of a Saccharomyces cerevisiae mutant with oversecretion
      phenotype.
AB  - An oversecreting mutant of Saccharomyces cerevisiae was obtained from about 400
      meiotic segregants derived from thediploid cells made by crossing the HBsAg
      induced mutant NI-C with the wild-type strain Sey6211. When transformed with a
      plasmid containing mouse alpha-amylase cDNA, the mutant (NI-C-D4) exhibited an
      increased capacity (up to 13-fold) for the secretion of mouse alpha-amylase,
      higher than the parental strains and other standard wild-type strains. It was
      also shown that alpha-amylase secreted by the oversecreting mutant had a higher
      activity and contained more of the non-glycosylated form than the glycosylated
      form. This isolated oversecreting, low-glycosylation mutant may prove to be a
      potential S. cerevisiae host for the production of foreign proteins. Further
      genetic analysis suggested that the mutation responsible for the mutant's
      oversecretion was partially dominant and that both the oversecretion and low
      glycosylation phenotypes were governed by a single chromosome mutation. These
      pleiotrophic phenotypes may be attributed to a defect in the synthesis of an ER
      resident chaperone.

PMID- 11525620
TI  - Expression of benzene dioxygenase from Pseudomonas putida ML2 in cis-1,2
      cyclohexanediol-degrading pseudomonads.
AB  - Benzene dioxygenase (BDO; EC 1.14.12.3) from Pseudomonas putida ML2
      dihydroxylates benzene to produce cis-1,2-dihydroxy-cyclohexa-3,5-diene. As well
      as oxidising benzene and toluene, cell-free extracts of Escherichia coli JM109
      expressing recombinant BDO oxidised cyclohexene, 1-methylcyclohexene and 3
      methylcyclohexene. In an attempt to construct a novel metabolic pathway for the
      degradation of cyclohexene (via an initial BDO-mediated dihydroxylation of
      cyclohexene), cis-1,2-cyclohexanediol-degrading bacteria were isolated by
      enrichment culture. The bedC1C2BA genes encoding BDO (under the control of the
      tac promoter) were sub-cloned into pLAFR5, successfully conjugated into seven of
      the Gram-negative cis-1,2-cyclo-hexanediol-degrading isolates and stably
      maintained and expressed in three of them. However, despite their ability to grow
      on cis-1,2-cyclohexanediol as sole carbon source, express an active BDO and
      oxidise cyclohexene, none of the three strains was able to grow on cyclohexene as
      sole carbon source. Analysis revealed that BDO oxidised cyclohexene to a mixture
      of two products, a monohydroxylated (2-cyclohexen-1-ol) product and a
      dihydroxylated (cis-1,2-cyclohexanediol) product; and failure to grow on
      cyclohexene was attributed to the toxicity of metabolic intermediates
      accumulating from the 2-cyclohexen-1-ol metabolism.

PMID- 11525621
TI  - Xanthomonas campestris pv. campestris secretes the endoglucanases ENGXCA and
      ENGXCB: construction of an endoglucanase-deficient mutant for industrial xanthan
      production.
AB  - Xanthomonas campestris pv. campestris secretes at least two cellulose-degrading
      endoglucanases. One of these endoglucanases is encoded by the engXCA gene of X.
      c. pv. campestris 8400 that was previously characterized by Gough et al. [Gene
      (1990) 89: 53-59]. An additional endoglucanase encoded by the engXCB gene was
      identified in X. c. pv. campestris 8400 and FC2. The engXCB gene product that was
      grouped into the endoglucanase family E contains a putative N-terminal signal
      peptide, suggesting a secretion by the type II secretion system. The ENGXCB
      protein contributed approximately 8% to the cellulase activity in xanthan
      preparations. Deletion of engXCA and engXCB resulted in a fivefold reduction of
      the cellulose-degrading activity in xanthan preparations. The cellulase activity
      determined in xanthan preparations of the engXCA-engXCB mutant was only slightly
      higher than the activity found in preparations that were subjected to heat
      treatment. Mutations in engXCA and engXCB did not affect the growth rate and
      xanthan production of X. c. pv. campestris FC2 under several cultivation
      conditions. The engXCA-engXCB deletion mutant is markerless, which makes this
      mutant a valuable strain for xanthan production and approaches aimed at
      inactivating further genes encoding extracellular enzymes.

PMID- 11525622
TI  - Molecular characterization of the actin-encoding gene and the use of its promoter
      for a dominant selection system in the methylotrophic yeast Hansenula polymorpha.
AB  - The actin gene (ACT) from the methylotrophic yeast Hansenula polymorpha was
      cloned and its structural feature was characterized. In contrast to the actin
      genes of other ascomycetous yeasts, which have only one large intron, the H.
      polymorpha ACT gene was found to be split by two introns. The H. polymorpha ACT
      introns were correctly processed in the heterologous host Saccharomyces
      cerevisiae despite appreciable differences in the splice site sequences. The
      promoter region of H. polymorpha ACT displayed two CCAAT motifs and two TATA-like
      sequences in a configuration similar to that observed in the S. cerevisiae actin
      promoter. A set of deleted H. polymorpha ACT promoters was exploited to direct
      expression of the bacterial hygromycin B resistance (hph) gene as a dominant
      selectable marker in the transformation of H. polymorpha. The resistance level of
      H. polymorpha transformants to the antibiotic was shown to be dependent on the
      integration copy number of the hph cassette. The selectivity of the hygromycin B
      resistance marker for transformants of higher copy number was remarkably
      increased with the deletion of the upstream TATA-like sequence, but not with the
      removal of either CCAAT motif, from the H. polymorpha promoter. The dosage
      dependent selection system developed in this study should be useful for genetic
      manipulation of H. polymorpha as an industrial strain to produce recombinant
      proteins.

PMID- 11525623
TI  - RAPD discrimination of Agaricus bisporus mushroom cultivars.
AB  - Cultivars of the white button mushroom Agaricus bisporus are difficult to
      differentiate, which has made strain protection problematic for this crop
      species. We have used RAPDs to discriminate between 26 strains of A. bisporus, 24
      of which were commercial cultivars, and to characterise the genetic relatedness
      of these strains. Using 20 primers, 211 RAPD markers were identified and used in
      hierarchical cluster, patristic distance and parsimony analyses. All strains
      could be differentiated using the aggregated primer data. Although no one primer
      could differentiate all 26 strains, several individual primers yielded unique
      fingerprints for a variety of strains. The greatest differences (up to 28%
      variation) were observed in comparisons with or between two wild collections of
      A. bisporus. Quondam cultivars, commercial brown and off-white varieties proved
      more variable than the widely grown 'hybrid' types. Of the 15 hybrid varieties
      analysed, only one differed substantially (20% or more variable). The patristic
      and parsimony analyses both demonstrated the gross similarity of the hybrids,
      many of which appear to be essentially derived varieties from two original hybrid
      cultivars. RAPD analyses can assist mushroom strain identification and could play
      a role in the protection of novel cultivars.

PMID- 11525624
TI  - Cloning, nucleotide sequence and expression of a hydantoinase and carbamoylase
      gene from Arthrobacter aurescens DSM 3745 in Escherichia coli and comparison with
      the corresponding genes from Arthrobacter aurescens DSM 3747.
AB  - The genes encoding hydantoinases (hyuH1) and carbamoylases (hyuC1) from
      Arthrobacter aurescens DSM 3745 and Arthrobacter aurescens DSM 3747 (hyuH2,
      hyuC2) were cloned in Escherichia coli and the nucleotide sequences determined.
      The hydantoinase genes comprised 1,377 base pairs and the carbamoylase genes
      1,239 base pairs each. Both hydantoinases, as well as both carbamoylases, showed
      a high degree of nucleotide and amino acid sequence identity (96-98%). The hyuH
      and hyuC genes were expressed in E. coli under the control of the rhamnose
      promoter and the different specific activities obtained in E. coli crude extracts
      were compared to those produced by the original hosts. For purification the hyuH2
      gene was expressed as a maltose-binding protein (MalE) and as an intein-chitin
      binding domain (CBD) fusion in E. coli. The expression of malE-hyuH2 resulted in
      the production of more soluble and active protein. With respect to temperature
      stability, optimal pH and optimal temperature, substrate and stereospecificity,
      the purified fusion enzyme exhibited properties similar to those of the wild-type
      enzyme.

PMID- 11525625
TI  - Biosynthesis of methionine from homocysteine, cystathionine and homoserine plus
      cysteine by mixed rumen microorganisms in vitro.
AB  - This study quantitatively investigated the biosynthesis of methionine (Met) and
      the production of related compounds from homocysteine (Hcys), cystathionine
      (Cysta), and homoserine (Hser) plus cysteine (Cys) by rumen bacteria (B) or
      protozoa (P) alone and by a mixture of these bacteria and protozoa (BP). Rumen
      contents were collected from fistulated goats to prepare the microbial
      suspensions and were anaerobically incubated at 39 degrees C for 12 h. Hcys,
      Cysta, and Hser plus Cys were catabolized by all rumen microbial fractions to
      different extents. B, P, and BP converted Hcys to Met with 2-aminobutyric acid
      (2AB) and methionine sulfoxide. The Met-producing ability of B (83.2 micromol g(
      1) microbial nitrogen; MN) from Hcys was about 3.6 times higher than that of P in
      a 6-h incubation period. The ability of BP, during the same incubation period,
      was about 30.0% higher than that of B. Hcys, Met, and 2AB were formed when Cysta
      was incubated with B, P, or BP. Rumen microbial fermentation of Hser plus Cys led
      to the formation of Cysta, Met (through Hcys), and 2AB. Thus the results
      indicated that a trans-sulfurylation pathway for Met synthesis was operating in
      the rumen bacteria and protozoa. The results mentioned above have been
      demonstrated for the first time in B, P, and BP in the present study.

PMID- 11525626
TI  - Attenuation of monochromatic and polychromatic lights in Chlorella vulgaris
      suspensions.
AB  - A quantitative description of light attenuation in microalgal suspensions is a
      prerequisite for kinetic modeling of microalgal photosynthesis and/or growth
      activity depending upon the light distribution inside photobioreactors. In this
      study, the light attenuation coefficients in Chlorella vulgaris suspensions were
      theoretically calculated from light absorption spectra and spectral irradiances
      of various light sources. By using this method, errors occurring in the direct
      measurement of the attenuation coefficients can be avoided. The obtained light
      attenuation coefficients were used for evaluating light attenuation models such
      as the Beer-Lambert, Cornet, and hyperbolic models. Furthermore, advantages and
      disadvantages of these models are discussed with respect to prediction of
      performance, mechanistic background, and usefulness for further application to
      calculation of the light distribution inside photobioreactors.

PMID- 11525627
TI  - Absence of aflatoxin biosynthesis in koji mold (Aspergillus sojae).
AB  - Ten strains isolated from industrial soy sauce producing koji mold were
      identified as Aspergillus sojae and distinguished from Aspergillus parasiticus
      morphologically and physiologically. There was no detectable aflatoxin in any
      culture extracts of A. sojae strains. Strain 477 was chosen as a representative
      strain of industrial A. sojae for further molecular analysis. All enzymatic
      activities associated with the aflatoxin biosynthesis were not detected or
      negligible in strain 477 compared with that of the A. parasiticus strain.
      Southern analysis suggested that the genomic DNA of strain 477 contained
      aflatoxin biosynthetic pathway genes. In contrast, all industrial strains lacked
      detectable transcripts of aflR, the main regulatory gene for aflatoxin
      biosynthesis, under the aflatoxin-inducing condition. Our data suggest that
      defects in aflR expression cause the lack of expression of aflatoxin-related
      genes which results in the absence of aflatoxin biosynthesis in A. sojae strains.

PMID- 11525628
TI  - Flocculation and coflocculation of bacteria by yeasts.
AB  - Biotransformations in natural environments frequently involve interactions
      between microorganisms. Although there are many reports on the interactions
      between bacteria, interactions between yeasts and bacteria have not been
      extensively studied. Previously we reported on the flocculation and
      coflocculation of Pediococcus damnosus by Saccharomyces cerevisiae. Now we report
      that several other yeasts, such as Candida utilis, Dekkera bruxellensis,
      Hanseniaspora guilliermondii, Kloeckera apiculata, and Schizosaccharomyces pombe,
      induce flocculation with several industrially or medically relevant bacteria,
      including Bacillus subtilis, Pseudomonas aeruginosa, and Staphylococcus aureus.
      Candida utilis was one of the best flocculation inducers. The results are
      discussed with respect to interactions between yeasts and bacteria and their
      applications in industry and medicine.

PMID- 11525629
TI  - Exopolysaccharides of Xanthomonas pathovar strains that infect rice and wheat
      crops.
AB  - In order to understand the mode of action of the taxonomically related pathogens
      Xanthomonas campestris pv. translucens, Xanthomonas oryzae pv. oryzae, and
      Xanthomonas oryzae pv. oryzicola, which attack wheat and rice crops, we examined
      the compositional differences of their exopolysaccharides (EPSs). Maximum
      production of polysaccharide in shake cultures of these pathogens was observed
      between 24 and 72 h. X. campestris pv. translucens, the leaf streak pathogen of
      wheat, produced a higher amount of polysaccharide (46.97 microg/ml) at 72 h
      compared to X. oryzae pv. oryzae (42.02 microg/ml), the bacterial blight pathogen
      of rice, and X. oryzae pv. oryzicola (41.91 microg/ml), the bacterial leaf streak
      pathogen of rice. Infrared (FTIR) spectra suggested that the polysaccharides of
      all three Xanthomonas pathovar strains have an -OH group with intermolecular
      hydrogen bonding, a C-H group of methyl alkanes, an aldehyde (RCHO) group, a C=C
      or C=O group, and a C-O group. FTIR spectra also revealed the presence of an acid
      anhydride group in X. oryzae pv. oryzae, a secondary aromatic or aliphatic amine
      group in X. campestris pv. translucens, and a primary aromatic or aliphatic amine
      group in X. oryzae pv. oryzae and X. oryzae pv. oryzicola. Nuclear magnetic
      resonance (NMR) spectra revealed the presence of unsubstituted sugars, an acetyl
      amine of hexose or pentose, and a beta-anomeric carbon of hexose or pentose in
      the polysaccharides of all bacteria. NMR spectra also identified the alpha
      anomeric carbon of hexose or pentose in all strains, and a branching at the
      fourth carbon of the sugar only in X. campestris pv. translucens; the presence of
      an uronic acid molecule (acid anhydride group) in X. oryzae pv. oryzae; and a
      deoxy sugar, rhamnose, in X. oryzae pv. oryzicola.

PMID- 11525630
TI  - Microbial sulfate reduction with acetate: process performance and composition of
      the bacterial communities in the reactor at different salinity levels.
AB  - Microbial sulfate reduction with acetate as carbon source and electron donor was
      investigated at salinity levels between 0.53 and 1.48%. The experiment was
      carried out in a 2.3-1 upflow anaerobic sludge blanket reactor inoculated with
      granular methanogenic sludge. A pH of 8.3, a temperature of 32 +/- 1 degrees C
      and a chemical oxygen demand (COD)/SO4(2-)-S ratio of 2 were maintained in the
      reactor throughout the experiment. Sulfate reduction and the composition of the
      dominant bacterial communities in the reactor were monitored. The results showed
      that a maximal conversion rate for SO4(2-)-S of 14 g l(-1) day(-1) and a
      conversion efficiency of more than 90% were obtained at a salinity level of 1.26
      1.39%. A further increase in the salinity level led to reactor instability.
      Denaturant gradient gel electrophoresis of 16S rDNA fragments amplified by PCR
      from total bacterial DNA extracted from the inoculum and reactor sludge showed
      that salinity level had an impact on the composition of the bacterial communities
      in the reactor. However, no clear relationship was found between reactor
      performance and the composition of the dominant bacterial communities in the
      reactor.

PMID- 11525631
TI  - Isolation and characterization of psychotrophic bacteria from oil-reservoir water
      and oil sands.
AB  - Four psychrotrophic strains, which grew at 4 degrees C but not at 37 degrees C,
      were isolated from Japanese oil-reservoir water (strains SIB1, SIC1, SIS1) and
      Canadian oil sands (strain CAB1). Strains SIB1, SIS1, and CAB1 had a maximum
      growth rate at 20 degrees C and grew to the highest cell densities at the
      cultivation temperature of 0-4 degrees C. Strain SIS1 was capable of growing even
      at -5 degrees C. The growth profile of strain SIC1 was rather similar to that of
      a mesophilic bacterium. Strains SIB1, SIC1, and SIS1 were identified as members
      of the genus Shewanella, and strain CAB1 was a member of the genus Arthrobacter.
      All these strains exhibited weak degradation ability against catechol, a
      hydroxylated aromatic hydrocarbon, and tributyrin. These strains are expected to
      be of potential use in the in situ bioremediation technology of hazardous
      hydrocarbons and esters under low-temperature conditions.

PMID- 11525632
TI  - Design of PCR primers and a gene probe for extensive detection of poly(3
      hydroxybutyrate) (PHB)-degrading bacteria possessing fibronectin type III linker
      type-PHB depolymerases.
AB  - For rapid and sensitive detection of poly(3-hydroxybutyrate) (PHB)-degrading
      bacteria, a PCR primer set (PHB primers) and a gene probe (PHB probe) were
      designed, based on the homologous regions of six fibronectin type III linker
      domain-encoding sequences laid on a variety of PHB depolymerase genes listed in
      the GenBank. PCR using PHB primers amplified DNA fragments with the expected
      sizes from all the tested bacterial strains used for primer design; and all of
      the amplified fragments gave positive signals by Southern hybridization with the
      PHB probe. No amplified fragments were observed from negative controls. To
      evaluate the availability of the PHB primers and PHB probe, they were applied to
      57 wild-type, PHB-degrading bacteria newly isolated from a variety of
      environments. The PHB primers amplified DNA fragments with expected sizes from 50
      of the 57 wild-type strains, while the PHB probe showed positive signals against
      the amplified fragments from 47 strains. These results suggest that the primer
      and probe system established in this study can detect a considerable proportion
      of the potential PHB-degrading bacteria and can be applied to evaluate PHB
      degradation potential in a natural environment, in combination with direct DNA
      extraction methods.

PMID- 11525634
TI  - Futile caspase-8 activation during the apoptotic cell death induced by DNA
      damaging agents in human B-lymphoblasts.
AB  - Caspase-8 plays an essential role in apoptosis induced by Fas activation.
      Moreover, caspase-8 can be processed also in response to exposure to genotoxic
      agents. To decipher the role of caspase-8 in DNA damaging agent (DDA)-induced
      apoptosis as well as the pathway(s) leading to its activation in response to
      genotoxic stress, we investigated caspase-8 processing induced by ionizing
      radiation (IR) or mitomycin C (MMC) treatment in human B-lymphoblasts.
      Altogether, our observations establish that caspase-8 is actively processed in
      both receptor-mediated and DDA-induced cell death. However, while Fas-dependent
      apoptosis absolutely required caspase-8 activity, it is not necessary for
      completion of the apoptotic program induced by IR and MMC. Experiments performed
      to understand the molecular pathway(s) of the caspase-8 activation after DDA
      demonstrated that for both IR and MMC, the Fas/Fas-L interaction is dispensable.
      Data obtained from caspase inhibitors and from lymphoblasts carrying mutations in
      ATM and FANCC proteins, involved in DDA response, clearly showed that distinct
      mechanisms are responsible for caspase-8 activation by IR and MMC in B
      lymphoblasts. IR-dependent processing of caspase-8 involves ATM, mitochondrial
      collapse, FANCC, and caspase-3 activation. Caspase-8 activation by MMC evokes the
      mitochondrial pathways involving FANCC but not ATM. Collectively, our data
      indicate that caspase-8 activation is essentially a bystander effect and not a
      major determinant of the behavior of DDA-exposed cells.

PMID- 11525635
TI  - Evidence for the Involvement of annexin 6 in the trafficking between the
      endocytic compartment and lysosomes.
AB  - Annexins are a family of calcium-dependent phospholipid-binding proteins, which
      have been implicated in a variety of biological processes including membrane
      trafficking. The annexin 6/lgp120 prelysosomal compartment of NRK cells was
      loaded with low-density lipoprotein (LDL) and then its transport from this
      endocytic compartment and its degradation in lysosomes were studied. NRK cells
      were microinjected with the mutated annexin 6 (anx6(1-175)), to assess the
      possible involvement of annexin 6 in the transport of LDL from the prelysosomal
      compartment. The results indicated that microinjection of mutated annexin 6, in
      NRK cells, showed the accumulation of LDL in larger endocytic structures,
      denoting retention of LDL in the prelysosomal compartment. To confirm the
      involvement of annexin 6 in the trafficking and the degradation of LDL we used
      CHO cells transfected with mutated annexin 6(1-175). Thus, in agreement with NRK
      cells the results obtained in CHO cells demonstrated a significant inhibition of
      LDL degradation in CHO cells expressing the mutated form of annexin 6 compared to
      controls overexpressing wild-type annexin 6. Therefore, we conclude that annexin
      6 is involved in the trafficking events leading to LDL degradation.

PMID- 11525636
TI  - Maintenance of nucleolar machineries and pre-rRNAs in remnant nucleolus of
      erythrocyte nuclei and remodeling in Xenopus egg extracts.
AB  - The nuclear functions in erythrocytes are almost completely extinct. There is no
      RNA polymerase I transcription, although a remnant nucleolar structure is still
      present. The remnant nucleolus of Xenopus laevis erythrocytes maintains a
      morphologically organized structure, nearly exclusively fibrillar. In this
      inactive nucleolar remnant, we revealed the presence of a modified form of
      transcription factor UBF. Several proteins of the processing machinery such as
      fibrillarin, nucleolin and B23/NO38, snoRNAs U3 and U8, and partially processed
      preribosomal RNAs colocalized in these remnant structures. Attempts to reprogram
      these erythrocyte nuclei in Xenopus egg extract showed that import of several
      nucleolar proteins was induced while the nucleolar remnant was disorganized. UBF
      became abundant and showed a necklace-like distribution on the decondensed
      ribosomal genes. Fibrillarin, nucleolin, and snoRNAs U3 and U8, also largely
      imported from the extract, were associated in large prenuclear bodies scattered
      in the nucleoplasm. B23/NO38 was present in different small bodies formed only in
      the most decondensed nuclei. In these remodeled erythrocyte nuclei, there was no
      imported preribosomal RNA and the initial presence of a residual nucleolar
      structure containing several partners of ribosome biogenesis was not sufficient
      to promote reassembly of newly imported nucleolar machineries. These nuclei,
      which reproduce the early events of nucleogenesis are also transcriptionally
      silent and thus compare to the early embryonic nuclei of Xenopus laevis.

PMID- 11525637
TI  - Soluble interleukin-6 receptor alpha inhibits the cytokine-Induced
      fractalkine/CX3CL1 expression in human vascular endothelial cells in culture.
AB  - Soluble form of IL-6 receptor alpha (sIL-6R) is known to serve as an agonist,
      without exogenous IL-6, on endothelial cells which do not express IL-6R but have
      only IL-6 receptor beta chain, gp130. We investigated the effect of sIL-6R on
      fractalkine expression in human umbilical vein endothelial cells (HUVECs) in
      culture. sIL-6R markedly inhibited HUVEC fractalkine/CX3CL1 expression induced by
      interleukin (IL)-1alpha, tumor necrosis factor (TNF)-alpha, or interferon (IFN)
      gamma. IL-1alpha-induced fractalkine expression was inhibited by sIL-6R in time-
      and concentration-dependent manners. The experiment using actinomycin D indicated
      that sIL-6R lowered the stability of fractalkine mRNA. The inhibitory effect of
      sIL-6R was reversed by anti-gp130 neutralizing antibody. sIL-6R inhibited
      adhesion of mononuclear cells (MNCs) to HUVEC monolayers stimulated with IFN
      gamma, but it did not inhibit the adhesion to monolayers stimulated with IL
      1alpha. MNC chemotactic activity of conditioned medium of HUVEC stimulated with
      IL-1alpha or IFN-gamma was inhibited by co-treatment with sIL-6R. sIL-6R may play
      a regulatory role in immune responses by modulating the interaction between
      leukocytes and the vascular endothelium.

PMID- 11525638
TI  - Upregulation of the cochaperone Mdg1 in endothelial cells is induced by stress
      and during in vitro angiogenesis.
AB  - Angiogenesis research has focused on receptors and ligands mediating endothelial
      cell proliferation and migration. Little is known about the molecular mechanisms
      that are involved in converting endothelial cells from a proliferative to a
      differentiated state. Microvascular differentiation gene 1 (Mdg1) has been
      isolated from differentiating microvascular endothelial cells that had been
      cultured in collagen type I gels (3D culture). In adult human tissue Mdg1 is
      expressed in endothelial and epithelial cells. Sequence analysis of the full
      length cDNA revealed that the N-terminal region of the putative Mdg1-protein
      exhibits a high sequence similarity to the J-domain of Hsp40 chaperones. We show
      that this region functions as a bona fide J-domain as it can replace the J-domain
      of Escherichia coli DnaJ-protein. Mdg1 is also upregulated in primary endothelial
      and mesangial cells when subjected to various stress stimuli. GFP-Mdg1 fusion
      constructs showed the Mdg1-protein to be localized within the cytoplasm under
      control conditions. Stress induces the translocation of Mdg1 into the nucleus,
      where it accumulates in nucleoli. Costaining with Hdj1, Hdj2, Hsp70, and Hsc70
      revealed that Mdg1 colocalizes with Hsp70 and Hdj1 in control and stressed HeLa
      cells. These data suggest that Mdg1 is involved in the control of cell cycle
      arrest taking place during terminal cell differentiation and under stress
      conditions.

PMID- 11525639
TI  - Cytotoxic effects of dynorphins through nonopioid intracellular mechanisms.
AB  - Dynorphin A, a prodynorphin-derived peptide, is able to induce neurological
      dysfunction and neuronal death. To study dynorphin cytotoxicity in vitro,
      prodynorphin-derived peptides were added into the culture medium of nonneuronal
      and neuronal cells or delivered into these cells by lipofection or
      electroporation. Cells were unaffected by extracellular exposure when peptides
      were added to the medium. In contrast, the number of viable cells was
      significantly reduced when dynorphin A or "big dynorphin," consisting of
      dynorphins A and B, was transfected into cells. Big dynorphin was more potent
      than dynorphin A, whereas dynorphin B; dynorphin B-29; [Arg(11,13)]-dynorphin A(
      13)-Gly-NH-(CH(2))(5)-NH(2), a selective kappa-opioid receptor agonist; and poly
      l-lysine, a basic peptide more positively charged than big dynorphin, failed to
      affect cell viability. The opioid antagonist naloxone did not prevent big
      dynorphin cytotoxicity. Thus, the toxic effects were structure selective but not
      mediated through opioid receptors. When big dynorphin was delivered into cells by
      lipofection, it became localized predominantly in the cytoplasm and not in the
      nuclei. Big dynorphin appeared to induce toxicity through an apoptotic mechanism
      that may involve synergistic interactions with the p53 tumor-suppressor protein.
      It is proposed that big dynorphin induces cell death by virtue of its net
      positive charge and clusters of basic amino acids that mimic (and thereby perhaps
      interfere with) basic domains involved in protein-protein interactions. These
      effects may be relevant for a pathophysiological role of dynorphins in the brain
      and spinal cord and for control of death of tumor cells, which express
      prodynorphin at high levels.

PMID- 11525640
TI  - Involvement of the MAP kinase pathways in induction of GADD45 following UV
      radiation.
AB  - The p53-regulated stress-inducible gene GADD45 has been shown to participate in
      cellular response to DNA damage, including cell cycle checkpoint, apoptosis, and
      DNA repair. However, the regulation of GADD45 expression is complex and may
      involve both p53-dependent and -independent pathways. Recent findings have
      demonstrated that the p53-independent induction of GADD45 is mainly regulated by
      the transcription factors Oct-1 and NF-YA, which directly bind to their consensus
      motifs located at the GADD45 promoter region. Here, we report that mitogen
      activated protein (MAP) kinases are involved in the induction of the GADD45
      promoter after DNA damage. Inhibition of JNK1 and ERK kinase activities either by
      expression of the dominant negative mutant JNK1 or by treatment with a selective
      chemical inhibitor of ERK (PD098059) substantially abrogates the UV induction of
      the GADD45 promoter. In contrast, a p38 kinase inhibitor (SB203580) has little
      effect on GADD45 induction by UV. In addition, the GADD45 promoter is strongly
      activated following expression of JNK1; Raf-1, which is an upstream activator of
      the ERK pathway; or MEK1, an upstream activator of both the ERK and the JNK
      pathways. Activation of the GADD45 promoter by MAP kinases does not require
      normal p53 function. Interestingly, the MAP kinase-regulatory effect appears to
      be mediated via OCT-1 and CAAT motifs since disruption of these sites abrogates
      activation of the GADD45 promoter by MAP kinases. Therefore, these findings
      indicate that the MAP kinase pathways are involved in the regulation of the p53
      independent induction of the GADD45 promoter, probably via interaction with
      transcription factors that directly bind to OCT-1 and CAAT motifs.

PMID- 11525641
TI  - Rho family GTPases regulate VEGF-stimulated endothelial cell motility.
AB  - Migration of endothelial cells induced by vascular endothelial growth factor
      (VEGF) is a critical step in angiogenesis. Stimulation of motility by growth
      factors such as VEGF requires interaction with the signal transduction pathways
      activated by the extracellular matrix (ECM). Here we demonstrate that the Rac
      GTPase is the critical intersection activated by type 1 collagen ECM and VEGF
      during stimulation of endothelial cell motility. To analyze the role of the Rho
      family GTPases in VEGF-stimulated endothelial cell chemotaxis and ECM-stimulated
      haptotaxis, we transduced the respective fusion proteins in human foreskin dermal
      endothelial cells using a Tat peptide from the human immunodeficiency virus Tat
      protein. VEGF signaling required Rac activation during chemotaxis, and Rac and
      Cdc42 were activated during haptotaxis on type I collagen. Similar to VEGF, Rac
      activation induced an increase in endothelial cell stress fiber and focal
      adhesion. Surprisingly, Rho activation was not present in collagen-induced
      haptotaxis or stimulation of chemotaxis by VEGF, although Rho induced stress
      fibers and focal adhesions similar to Rac activation. The result of constitutive
      Rho activation was an inhibition of haptotaxis. Thus, Rac is required and
      sufficient for the activation of endothelial cell haptotaxis and VEGF-stimulated
      chemotaxis.

PMID- 11525642
TI  - Smooth muscle cell response to mechanical injury involves intracellular calcium
      release and ERK1/ERK2 phosphorylation.
AB  - We have investigated possible signaling pathways coupled to injury-induced ERK1/2
      activation and the subsequent initiation of vascular rat smooth muscle cell
      migration and proliferation. Aortic smooth muscle cells were cultured to
      confluency and subjected to in vitro injury under serum-free conditions. In fluo
      4-loaded cells, injury induced a rapid wave of intracellular Ca(2+) release that
      propagated about 200 microm in radius from the injured zone, reached a peak in
      about 20 s, and subsided to the baseline within 2 min. The wave was abolished by
      prior treatment with the sarcoplasmic reticulum ATPase inhibitor thapsigargin,
      but not by omission of extracellular Ca(2+). ERK1/2 activation reached a peak at
      10 min after injury and was inhibited by the MEK1 inhibitor PD98059, as well as
      by thapsigargin, fluphenazine, genistein, and the Src inhibitor PP2. These
      inhibitors also reduced [(3)H]thymidine incorporation and migration of cells into
      the injured area determined at 48 h after injury. These results show that
      mechanical injury to vascular smooth muscle cells induces a Ca(2+) wave which is
      dependent on intracellular Ca(2+) release. Furthermore, the injury activates
      ERK1/2 phosphorylation as well as cell migration and replication.

PMID- 11525643
TI  - Protein kinase Calpha expression confers retinoic acid sensitivity on MDA-MB-231
      human breast cancer cells.
AB  - Retinoic acid activation of retinoic acid receptor alpha (RARalpha) induces
      protein kinase Calpha (PKCalpha) expression and inhibits proliferation of the
      hormone-dependent T-47D breast cancer cell line. Retinoic acid has no effect on
      proliferation or PKCalpha expression in a hormone-independent, breast cancer cell
      line (MDA-MB-231). To test the role of PKCalpha in retinoic acid-induced growth
      arrest of human breast cancer cells we established MDA-MB-231 cell lines stably
      expressing PKCalpha. Constitutive expression of PKCalpha did not affect
      proliferation of MDA-MB-231 cells but did result in partial retinoic acid
      sensitivity. Retinoic acid treatment of PKCalpha-MDA-MB-231 cells decreased
      proliferation (by approximately 40%) and inhibited serum activation of MAP
      kinases and induction of c-fos. Similar results were seen in MDA-MB-231 cells in
      which transcription of the transfected PKCalpha cDNA was reversibly induced by
      isopropyl beta-d-thiogalactoside. Expression of RARalpha in PKCalpha expressing
      MDA-MB-231 cells resulted in even greater retinoic acid responses, as measured by
      effects on cell proliferation, inhibition of serum signaling, and transactivation
      of an RARE-CAT reporter plasmid. In summary, PKCalpha synergizes with activated
      RARalpha to disrupt serum growth factor signaling, ultimately arresting
      proliferation of MDA-MB-231 cells.

PMID- 11525644
TI  - Endogenous IL-1 and type II IL-1 receptor expression modulate anoikis in
      intestinal epithelial cells.
AB  - We previously reported that IL-1beta and the decoy receptor for IL-1 (IL-1RII)
      are expressed by intestinal epithelial cells (IEC) during detachment-induced cell
      death, or "anoikis." We now investigated whether IL-1 regulates anoikis. Skewing
      the balance in favor of IL-1, by blocking IL-1RII or by adding IL-1beta to
      detached rat IEC-18 cells, reduced cell death. The protective effect of anti-IL
      1RII was reversed by blocking IL-1beta, confirming the anti-apoptotic effect was
      due to endogenous IL-1beta. Added IL-1beta also rescued cells from anoikis and
      was associated with considerable aggregation of the detached cells. Aggregate
      formation and the anti-apoptotic effect of added IL-1beta were prevented by
      blocking E-cadherin, indicating that IL-1 promoted aggregation and indirectly,
      survival. On the other hand, treating detached cells with IL-1beta and an anti
      beta(1) integrin antibody abolished the protective effect of IL-1beta but not the
      aggregates. We conclude that the anti-apoptotic effect of IL-1 is mediated
      through a beta(1) integrin-dependent event secondary to cell-cell adhesion. This
      illustrates a previously uncharacterized role for IL-1 in the intestine wherein
      this cytokine may facilitate the preservation of the epithelial monolayer
      integrity.

PMID- 11525646
TI  - Reproductive maternal centrosomes are cast off into polar bodies during
      maturation division in starfish oocytes.
AB  - Animal egg inherits a maternal centrosome from the meiosis-II spindle and sperm
      can introduce another centrosome at fertilization. It has been believed that in
      most animals only the sperm centrosome provides the division poles for mitosis in
      zygotes. This uniparental (paternal) inheritance of the centrosome must depend on
      the loss of the maternal centrosome. In starfish, suppression of polar body (PB)
      extrusion is a prerequisite for induction of parthenogenesis (Washitani-Nemoto et
      al. (1994) Dev. Biol. 163, 293-301), suggesting that the centrosomes cast off
      into PBs have reproducing capacity. Due to the absence of centriole duplication
      in meiosis II of starfish oocytes, each centrosome of a meiosis-II spindle has
      only one single centriole, whereas in meiosis I each has a pair of centrioles
      (Sluder et al. (1989) Dev. Biol. 131, 567-579; Kato et al. (1990) Dev. Growth
      Differ. 32, 41-49). Hence, the first PB (PB1) has two centrioles, whereas the
      second PB (PB2) and the mature egg have only one centriole, respectively. The
      present study examined the reproductive capacity of PB centrosomes by
      transplanting them into artificially activated eggs, and then the recipient egg
      nucleus with the surrounding cytoplasm was removed. A transplanted PB2 centrosome
      with a single centriole formed a monopolar spindle at the first mitosis, followed
      by formation of a bipolar spindle in the next mitosis, leading to actual cleavage
      and subsequent development. This proves the reproducing capacity of the single
      centriole in the PB2 centrosome. The behavior of the transplanted PB1 centrosome
      was exactly the same as in the PB2 centrosome, in spite of the difference in the
      number of centrioles. These results clearly show that four maternal centrioles
      are heterogeneous in duplicating capacity, during meiosis only one centriole in
      each of the centrosomes of a meiosis-I spindle pole retains duplicating capacity,
      the reproductive centrioles are successively cast off into PBs, and finally a
      mature egg inheriting a nonreproductive centriole alone is formed, and the
      presence of a single reproductive centriole is sufficient condition for embryonic
      development in starfish.

PMID- 11525645
TI  - A verotoxin 1 B subunit-lambda CRO chimeric protein specifically binds both DNA
      and globotriaosylceramide (Gb(3)) to effect nuclear targeting of exogenous DNA in
      Gb(3) positive cells.
AB  - Inefficient nuclear incorporation of foreign DNA remains a critical roadblock in
      the development of effective nonviral gene delivery systems. DNA delivered by
      traditional protocols remains within endosomal/lysosomal vesicles, or is rapidly
      degraded in the cytoplasm. Verotoxin I (VT), an AB(5) subunit toxin produced by
      enterohaemorrhagic Escherichia coli, binds to the cell surface glycolipid,
      globotriaosylceramide (Gb(3)) and is internalized into preendosomes. VT is then
      retrograde transported to the Golgi, endoplasmic reticulum (ER), and nucleus of
      highly VT-sensitive cells. We have utilized this nuclear targeting of VT to
      design a unique delivery system which transports exogenous DNA via vesicular
      traffic to the nucleus. The nontoxic VT binding subunit (VTB) was fused to the
      lambda Cro DNA-binding repressor, generating a 14-kDa VTB-Cro chimera. VTB-Cro
      binds specifically via the Cro domain to a 25-bp DNA fragment containing the
      consensus Cro operator. VTB-Cro demonstrates simultaneous specific binding to
      Gb(3). Treatment of Vero cells with fluorescent-labeled Cro operator DNA in the
      presence of VTB-Cro, results in DNA internalization to the Golgi, ER, and
      nucleus, whereas fluorescent DNA alone is incorporated poorly and randomly within
      the cytoplasm. VTB-Cro mediated nuclear DNA transport is prevented by brefeldin
      A, consistent with Golgi/ER intracellular routing. Pretreatment with filipin had
      no effect, indicating that caveoli are not involved. This novel VTB-Cro shuttle
      protein may find practical applications in the fields of intracellular targeting,
      gene delivery, and gene therapy.

PMID- 11525647
TI  - Micromechanics of fibroblast contraction of a collagen-GAG matrix.
AB  - The contractile force developed by fibroblasts has been studied by measuring the
      macroscopic contraction of porous collagen-GAG matrices over time. We have
      identified the microscopic deformations developed by individual fibroblasts which
      lead to the observed macroscopic matrix contraction. Observation of live cells
      attached to the matrix revealed that matrix deformation occurred as a result of
      cell elongation. The time dependence of the increase in average fibroblast aspect
      ratio over time corresponded with macroscopic matrix contraction, further linking
      cell elongation and matrix contraction. The time dependence of average fibroblast
      aspect ratio and macroscopic matrix contraction was found to be the result of the
      stochastic nature of cell elongation initiation and of the time required for
      cells to reach a final morphology (2-4 h). The proposed micromechanics associated
      with observed buckling or bending of individual struts of the matrix by cells
      may, in part, explain the observation of a force plateau during macroscopic
      contraction. These findings indicate that the macroscopic matrix contraction
      measured immediately following cell attachment is related to the extracellular
      force necessary to support cell elongation, and that macroscopic time dependence
      is not directly related to microscopic deformation events.

PMID- 11525648
TI  - Protein kinase C-dependent upregulation of N-cadherin expression by phorbol ester
      in human calvaria osteoblasts.
AB  - Cell-cell adhesion mediated by cadherins is believed to play an essential role in
      the control of cell differentiation and tissue formation. Our recent studies
      indicate that N-cadherin is involved in human osteoblast differentiation.
      However, the signalling molecules that regulate cadherins in osteoblasts are not
      known. We tested the possibility that N-cadherin expression and function may be
      regulated by direct activation of protein kinase C (PKC) in human osteoblasts.
      Treatment of immortalized human neonatal calvaria (IHNC) cells with phorbol 12,13
      dibutyrate (100 nM) transiently increased PKC activity. RT-PCR analysis showed
      that transient treatment with phorbol ester transiently increased N-cadherin mRNA
      levels at 4-12 h. Western blot analysis showed that N-cadherin protein levels
      were increased by phorbol ester at 24-48 h, and this was confirmed by
      immunocytochemical analysis. In contrast, E-cadherin expression was not affected.
      Transient treatment of IHNC cells with phorbol ester increased cell-cell
      aggregation, which was suppressed by neutralizing N-cadherin antibody, showing
      that the increased N-cadherin induced by phorbol ester was functional. Finally,
      phorbol ester dose-dependently increased alkaline phosphatase activity, an early
      marker of osteoblast differentiation. This effect was comparable to the promoting
      effect of BMP-2, a potent activator of osteoblast differentiation. These data
      show that direct activation of PKC by phorbol ester increases N-cadherin
      expression and function, and promotes ALP activity in human calvaria osteoblasts,
      which provides a signaling mechanism by which N-cadherin is regulated and
      suggests a role for PKC in N-cadherin-mediated control of human osteoblast
      differentiation.

PMID- 11525649
TI  - Differences in patterns of activation of MAP kinases induced by oncogenic ras-p21
      and insulin in oocytes.
AB  - Oncogenic ras (Val 12-containing)-p21 protein induces oocyte maturation by a
      pathway that is blocked by peptides from effector domains of ras-p21, i.e.,
      residues 35-47 (that block Val 12-p21-activated raf) and 96-110 and 115-126,
      which do not affect the ability of insulin-activated cellular p21 to induce
      maturation. Oncogenic p21 binds directly to jun-N-terminal kinase (JNK), which is
      blocked by the p21 96-110 and 115-126 peptides. This finding predicts that
      oncogenic p21, but not insulin, induces maturation by early and sustained
      activation of JNK. We now directly confirm this prediction by showing that
      oncogenic p21 induces activating phosphorylation of JNK (JNK-P) and of ERK (MAP
      kinase) (MAPK-P), whose levels correlate with oocyte maturation. p21 peptides 35
      47 and 96-110 block formation of JNK-P and MAPK-P, further confirming this
      correlation and suggesting, unexpectedly, that raf-MEK-MAPK and JNK-jun pathways
      strongly interact on the oncogenic p21 pathway. In contrast, insulin activates
      only low levels of JNK-P, and, surprisingly, we find that insulin induces only
      low levels of MAPK-P, indicating that insulin and activated normal p21 utilize
      MAP kinase-independent signal transduction pathways.

PMID- 11525650
TI  - Direct pK(a) measurement of the active-site cytosine in a genomic hepatitis delta
      virus ribozyme.
AB  - Hepatitis delta virus ribozymes have been proposed to perform self-cleavage via a
      general acid/base mechanism involving an active-site cytosine, based on evidence
      from both a crystal structure of the cleavage product and kinetic measurements.
      To determine whether this cytosine (C75) in the genomic ribozyme has an altered
      pK(a) consistent with its role as a general acid or base, we used (13)C NMR to
      determine its microscopic pK(a) in the product form of the ribozyme. The measured
      pK(a) is moderately shifted from that of a free nucleoside or a base-paired
      cytosine and has the same divalent metal ion dependence as the apparent reaction
      pK(a)'s measured kinetically. However, under all conditions tested, the
      microscopic pK(a) is lower than the apparent reaction pK(a), supporting a model
      in which C75 is deprotonated in the product form of the ribozyme at physiological
      pH. While additional results suggest that the pK(a) is not shifted in the
      reactant state of the ribozyme, these data cannot rule out elevation of the C75
      pK(a) in an intermediate state of the transesterification reaction.

PMID- 11525651
TI  - Noncovalently functionalized dendrimers as recyclable catalysts.
AB  - The efficient reversible functionalization of the periphery of urea adamantyl
      poly(propylene imine) dendrimers with catalytic sites using noncovalent
      interactions is described. Phosphine ligands equipped with urea acetic groups, a
      binding motive complementary to that of the dendrimer host, have been prepared
      and assembled to the dendrimer support. The resulting supramolecular complex has
      been used as a multidentate ligand system in the palladium-catalyzed allylic
      amination reaction in a batch process and in a continuous-flow membrane reactor.
      We found that the activity and selectivity of the dendrimeric complex is similar
      to that of the monomer complex, which indicates that the catalytic centers act as
      independent sites. The size of the supramolecular system is sufficiently large
      and the binding of the guests is strong enabling a good separation of the
      catalyst components from the reaction mixture using nanofiltration techniques.

PMID- 11525652
TI  - Photoalkylation of 10-alkylacridinium ion via a charge-shift type of photoinduced
      electron transfer controlled by solvent polarity.
AB  - A charge-shift type of photoinduced electron-transfer reactions from various
      electron donors to the singlet excited state of 10-decylacridinium cation
      (DeAcrH+) in a nonpolar solvent (benzene) is found to be as efficient as those of
      10-methylacridinium cation (MeAcrH+) and DeAcrH+ in a polar solvent
      (acetonitrile). Irradiation of the absorption bands of MeAcrH+ in acetonitrile
      solution containing tetraalkyltin compounds (R(4)Sn) results in the efficient and
      selective reduction of MeAcrH+ to yield the 10-methyl-9-alkyl-9,10
      dihydroacridine (AcrHR). The same type of reaction proceeds in benzene when
      MeAcrH+ is replaced by DeAcrH+ which is soluble in benzene. The photoalkylation
      of R'AcrH+ (R' = Me and De) also proceeds in acetonitrile and benzene using 4
      tert-butyl-1-benzyl-1,4-dihydronicotinamide (Bu(t)BNAH) instead of R(4)Sn,
      yielding MeAcrHBu(t). The quantum yield determinations, the fluorescence
      quenching of R'AcrH+ by electron donors, and direct detection of the reaction
      intermediates by means of laser flash photolysis experiments indicate that the
      photoalkylation of R'AcrH+ in benzene as well as in acetonitrile proceeds via
      photoinduced electron transfer from the alkylating agents (R(4)Sn and Bu(t)BNAH)
      to the singlet excited states of R'AcrH+. The limiting quantum yields are
      determined by the competition between the back electron-transfer process and the
      bond-cleavage process in the radical pair produced by the photoinduced electron
      transfer. The rates of back electron transfer have been shown to be controlled by
      the solvent polarity which affects the solvent reorganization energy of the back
      electron transfer. When the free energy change of the back electron transfer
      (DeltaG(0)(bet)) in a polar solvent is in the Marcus inverted region, the rate of
      back electron transfer decreases with decreasing the solvent polarity, leading to
      the larger limiting quantum yield for the photoalkylation reaction. In contrast,
      the opposite trend is obtained when the DeltaG(0)(bet) value is in the normal
      region: the limiting quantum yield decreases with decreasing the solvent
      polarity.

PMID- 11525653
TI  - A silica-supported, switchable, and recyclable hydroformylation-hydrogenation
      catalyst.
AB  - A homogeneous hydroformylation catalyst, designed to produce selectively linear
      aldehydes, was covalently tethered to a polysilicate support. The immobilized
      transition-metal complex [Rh(A)CO]+(1+)), in which A is N-(3-trimethoxysilane-n
      propyl)-4,5-bis(diphenylphosphino)phenoxazine, was prepared both via the sol-gel
      process and by covalent anchoring to silica. 1+ was characterized by means of
      (31)P and (29)Si MAS NMR, FT-IR, and X-ray photoelectron spectroscopy.
      Polysilicate immobilized Rh(A) performed as a selective hydroformylation catalyst
      showing an overall selectivity for the linear aldehyde of 94.6% (linear to
      branched aldehyde ratio of 65). In addition 1-nonanol, obtained via the
      hydrogenation of the corresponding aldehyde, was formed as an unexpected
      secondary product (3.6% at 20% conversion). Under standard hydroformylation
      conditions, 1+ and HRh(A)(CO)(2)(1) coexist on the support. This dual catalyst
      system performed as a hydroformylation/hydrogenation sequence catalyst (Z),
      giving selectively 1-nonanol from 1-octene; ultimately, 98% of 1-octene was
      converted to mainly 1-nonanal and 97% of the nonanal was hydrogenated to 1
      nonanol. The addition of 1-propanol completely changes Z in a hydroformylation
      catalyst (X), which produces 1-nonanal with an overall selectivity of 93%, and
      completely suppresses the reduction reaction. If the atmosphere is changed from
      CO/H(2) to H(2) the catalyst system is switched to the hydrogenation mode (Y),
      which shows a clean and complete hydrogenation of 1-octene and 1-nonanal within
      24 h. The immobilized catalyst can be recycled and the system can be switched
      reversibly between the three "catalyst modes" X, Y, and Z, completely retaining
      the catalyst performance in each mode.

PMID- 11525654
TI  - 2-(Hydroxycarbonyl)benzyl glycosides: a novel type of glycosyl donors for highly
      efficient beta-mannopyranosylation and oligosaccharide synthesis by latent-active
      glycosylation.
AB  - 2-(Benzyloxycarbonyl)benzyl (BCB) glycosides were prepared by coupling of the
      corresponding tetraacetylglycosyl bromides and benzyl 2-(hydroxymethyl)benzoate.
      The BCB glycosides were converted almost quantitatively into the corresponding 2
      (hydroxycarbonyl)benzyl (HCB) glycosides by selective hydrogenolysis of the
      benzyl ester functionality without affecting the benzylidene acetal and the
      benzyl ether. Treatment of the HCB 4,6-O-benzylidenemannopyranoside 4 with
      triflic anhydride in the presence of di-tert-butylmethylpyridine and subsequent
      addition of the glycosyl acceptor having a primary hydroxyl group afforded
      exclusively the disaccharide of the beta-mannopyranosyl linkage. Glycosylation of
      the compound 4 with secondary and tertiary alcohols also provided beta
      mannopyranosides as the major products. Glycosylation of the HCB 4,6-O
      cyclohexylidenemannoside 5 with primary alcohols was also highly beta-selective,
      and the HCB 2,3-O-cyclohexylidenemannoside 6 exhibited the moderate beta
      selectivity. On the other hand, unlike the HCB mannosides, the HCB 4,6-O
      benzylideneglucoside 7 gave exclusively the disaccharides of the alpha
      glycopyranosyl linkage in the glycosylation with primary alcohols. The latent BCB
      disaccharide 23, which was obtained from the HCB mannoside 4 as the donor and the
      BCB glucoside 12 as the acceptor by the present glycosylation method, was
      converted into the active HCB-disaccharide 39 by selective hydrogenolysis.
      Repetitive glycosylation of the donor 39 with the same acceptor 12 afforded the
      BCB-trisaccharide 40. Other BCB-trisaccharides 42 and 46 were also efficiently
      synthesized by employing the present methodology.

PMID- 11525655
TI  - Formation, isolation, spectroscopic properties, and calculated properties of some
      isomers of C(60)H(36).
AB  - Isomers of C(60)H(36) and He@C(60)H(36) have been synthesized by the Birch or
      dihydroanthracene reduction of C(60) and isolated by preparative high-pressure
      liquid chromatography. (3)He, (13)C, and (1)H NMR spectroscopic properties were
      then determined. A comparison of experimental chemical shifts against those
      computed using density functional theory (B3LYP) with polarized triple- and
      double-zeta basis sets for He and C,H, respectively, allowed provisional
      assignment of structure for several isomers to be made. Theoretical calculations
      have also been carried out to identify low-energy structures. The transfer
      hydrogenation method using dihydroanthracene gives a major C(60)H(36) isomer and
      a minor C(60)H(36) isomer with C(3) symmetry as determined by the (13)C NMR
      spectrum of C(60)H(36) and the (3)He NMR spectrum of the corresponding sample of
      (3)He@C(60)H(36). In view of the HPLC retention times and the (3)He chemical
      shifts observed for the Birch and dihydroanthracene reduction products, the two
      isomers generated by the latter procedure can be only minor isomers of the Birch
      reduction. A significant energy barrier apparently exists in the
      dihydroanthracene reduction of C(60) for the conversion of the C(3) and C(1)
      symmetry isomers of C(60)H(36) to the T symmetry isomer previously predicted by
      many calculations to be among the most stable C(60)H(36) isomers. Many of the
      (1)H NMR signals exhibited by C(60)H(36) (and C(60)H(18), previously reported)
      are unusually deshielded compared to "ordinary" organic compounds, presumably
      because the unusual structures of C(60)H(36) and C(60)H(18) result in chemical
      shift tensors with one or more unusual principal values. Calculations clearly
      show a relationship between exceptionally deshielded protons beta to a benzene
      ring in C(60)H(18) and C(60)H(36) and relatively long C-C bonds associated with
      these protons. The additional information obtained from 1D and 2D (1)H NMR
      spectra obtained at ultrahigh field strengths (up to 900 MHz) will serve as a
      critical test of chemical shifts to be obtained from future calculations on
      different C(60)H(36) isomers.

PMID- 11525656
TI  - Synthesis of propionate motifs: diastereoselective tandem reactions involving
      anionic and free radical based processes.
AB  - Reported herein is a strategy employing a Mukaiyama reaction in tandem with a
      hydrogen transfer reaction for the elaboration of propionate motifs. The nature
      of the protecting groups on the chiral beta-alkoxy aldehyde and the type of Lewis
      acid used are varied to modulate the stereochemical outcome of the tandem
      reactions. The mode of complexation is thus controlled (monodentate or chelate)
      for the Mukaiyama reaction to give access to either syn or anti aldol products,
      precursors of the free radical reduction reaction. The endocyclic effect is
      subsequently capitalized upon to control the hydrogen transfer step so that the
      syn-reduced product may be achieved. Proceeding with excellent yield and
      diastereoselectivity, the synthetic sequence proposed gives access to syn-syn and
      syn-anti propionate motifs. Also considered is a complementary approach using a
      chelation-controlled Mukaiyama reaction in tandem with a free radical allylation
      reaction under the control of the endocyclic effect that leads to the anti-anti
      product.

PMID- 11525657
TI  - N-dealkylation of an N-cyclopropylamine by horseradish peroxidase. Fate of the
      cyclopropyl group.
AB  - Cyclopropylamines inactivate cytochrome P450 enzymes which catalyze their
      oxidative N-dealkylation. A key intermediate in both processes is postulated to
      be a highly reactive aminium cation radical formed by single electron transfer
      (SET) oxidation of the nitrogen center, but direct evidence for this has remained
      elusive. To address this deficiency and identify the fate of the cyclopropyl
      group lost upon N-dealkylation, we have investigated the oxidation of N
      cyclopropyl-N-methylaniline (3) by horseradish peroxidase, a well-known SET
      enzyme. For comparison, similar studies were carried out in parallel with N
      isopropyl-N-methylaniline (9) and N,N-dimethylaniline (8). Under standard
      peroxidatic conditions (HRP, H(2)O(2), air), HRP oxidizes 8 completely to N
      methylaniline (4) plus formaldehyde within 15-30 min, whereas 9 is oxidized more
      slowly (<10% in 60 min) to produce only N-isopropylaniline (10) and formaldehyde
      (acetone and 4 are not formed). In contrast to results with 9, oxidation of 3 is
      complete in <60 min and affords 4 (20% yield) plus traces of aniline. By using
      [1'-(14)C]-3, [1'-(13)C]-3, and [2',3'-(13)C]-3 as substrates, radiochemical and
      NMR analyses of incubation mixtures revealed that the complete oxidation of 3 by
      HRP yields 4 (0.2 mol), beta-hydroxypropionic acid (17, 0.2 mol), and N
      methylquinolinium (16, 0.8 mol). In buffer purged with pure O(2), the complete
      oxidation of 3 yields 4 (0.7 mol), 17 (0.7 mol), and 16 (0.3 mol), while under
      anaerobic conditions, 16 is formed quantitatively from 3. These results indicate
      that the aminium ion formed by SET oxidation of 3 undergoes cyclopropyl ring
      fragmentation exclusively to generate a distonic cation radical (14+*) which then
      partitions between unimolecular cyclization (leading, after further oxidation, to
      16) and bimolecular reaction with dissolved oxygen (leading to 4 and 17 in a 1:1
      ratio). Neither beta-hydroxypropionaldehyde, acrolein, nor cyclopropanone hydrate
      are formed as SET metabolites of 3. The synthetic and analytical methods
      developed in the course of these studies should facilitate the application of
      cyclopropylamine-containing probes to reactions catalyzed by cytochrome P450
      enzymes.

PMID- 11525658
TI  - Synthesis and absolute stereochemistry of roseophilin.
AB  - The enantiospecific total synthesis of natural roseophilin has been completed in
      7.0% overall yield over 15 steps by means of an asymmetric cyclopentannelation.
      This establishes the absolute configuration of the natural product as 22R,23R.
      Cyclopentenone (+)-12 was prepared in 78% yield and 86% ee in the key step.

PMID- 11525659
TI  - Asymmetric total synthesis of ent-(-)-roseophilin: assignment of absolute
      configuration.
AB  - An asymmetric total synthesis of ent-(-)-roseophilin (1), the unnatural
      enantiomer of a novel naturally occurring antitumor antibiotic, is described. The
      approach enlists a room temperature heterocyclic azadiene inverse electron demand
      Diels-Alder reaction of dimethyl 1,2,4,5-tetrazine-3,6-dicarboxylate (7) with the
      optically active enol ether 6 bearing the C23 chiral center followed by a
      reductive ring contraction reaction for formation of an appropriately
      functionalized pyrrole ring in a key 1,2,4,5-tetrazine --> 1,2-diazine -->
      pyrrole reaction sequence. A Grubbs' ring closing metathesis reaction was
      utilized to close the unusual 13-membered macrocycle prior to a subsequent 5-exo
      trig acyl radical-alkene cyclization that was used to introduce the fused
      cyclopentanone and complete the preparation of the tricylic ansa-bridged
      azafulvene core 32. Condensation of 32 with 33 under the modified conditions of
      Tius and Harrington followed by final deprotection provided (22S,23S)-1.
      Comparison of synthetic (22S,23S)-1 ([alpha](25)(D), CD) with natural 1
      established that they were enantiomers and enabled the assignment of the absolute
      stereochemistry of the natural product as 22R,23R. Surprisingly, ent-(-)-1 was
      found to be 2-10-fold more potent than natural (+)-1 in cytotoxic assays,
      providing an unusually rewarding culmination to synthetic efforts that provided
      the unnatural enantiomer.

PMID- 11525660
TI  - Novel bifunctional periodic mesoporous organosilicas, BPMOs: synthesis,
      characterization, properties and in-situ selective hydroboration-alcoholysis
      reactions of functional groups.
AB  - A new class of bifunctional periodic mesoporous organosilicas (BPMOs) containing
      two differently bonded organic moieties in a mesoporous host has been synthesized
      and characterized. By incorporating bridge-bonded ethylene groups into the walls
      and terminally bonded vinyl groups protruding into the channel space, both the
      chemistry and physical properties of the resulting BPMO could be modified. The
      materials have periodic mesoporous structures in which the bridging ethylene
      plays a structural and mechanical role and the vinyl groups are readily
      accessible for chemical transformations. The vinyl groups in the material
      underwent hydroboration with BH(3).THF and the resulting organoborane in the BPMO
      was quantitatively transformed into an alcohol using either H(2)O(2)/NaOH or
      NaBO(3).4H(2)O. The materials retained ordered structures after subsequent in
      situ reactions with largely unchanged pore volumes, specific surface areas and
      pore size distributions. Other organic functionalized BPMO materials may be
      synthesized in a similar manner or by further functionalizing the resulting
      borylated or alcohol functionalized BPMO materials. The thermal properties of the
      BPMO materials have also been investigated and are compared to those of the
      periodic mesoporous organosilica (PMO) materials. Noteworthy thermal events
      concern intrachannel reactions between residual silanols or atmospheric oxygen
      and organics in BPMOs. They begin around 300 degrees C and smoothly interconvert
      bridging ethylene to terminal vinyl groups and terminal vinyl to gaseous ethene
      and ethane, ultimately producing periodic mesoporous silica at 900 degrees C that
      exhibits good structural order and a unit-cell size decreased relative to that of
      the parent BPMO.

PMID- 11525661
TI  - Electron and oxygen transfer in polyoxometalate, H(5)PV(2)Mo(10)O(40), catalyzed
      oxidation of aromatic and alkyl aromatic compounds: evidence for aerobic Mars-van
      Krevelen-type reactions in the liquid homogeneous phase.
AB  - The mechanism of aerobic oxidation of aromatic and alkyl aromatic compounds using
      anthracene and xanthene, respectively, as a model compound was investigated using
      a phosphovanadomolybdate polyoxometalate, H(5)PV(2)Mo(10)O(40), as catalyst under
      mild, liquid-phase conditions. The polyoxometalate is a soluble analogue of
      insoluble mixed-metal oxides often used for high-temperature gas-phase
      heterogeneous oxidation which proceed by a Mars-van Krevelen mechanism. The
      general purpose of the present investigation was to prove that a Mars-van
      Krevelen mechanism is possible also in liquid-phase, homogeneous oxidation
      reactions. First, the oxygen transfer from H(5)PV(2)Mo(10)O(40) to the
      hydrocarbons was studied using various techniques to show that commonly observed
      liquid-phase oxidation mechanisms, autoxidation, and oxidative nucleophilic
      substitution were not occurring in this case. Techniques used included (a) use of
      (18)O-labeled molecular oxygen, polyoxometalate, and water; (b) carrying out
      reactions under anaerobic conditions; (c) performing the reaction with an
      alternative nucleophile (acetate) or under anhydrous conditions; and (d)
      determination of the reaction stoichiometry. All of the experiments pointed
      against autoxidation and oxidative nucleophilic substitution and toward a Mars
      van Krevelen mechanism. Second, the mode of activation of the hydrocarbon was
      determined to be by electron transfer, as opposed to hydrogen atom transfer from
      the hydrocarbon to the polyoxometalate. Kinetic studies showed that an outer
      sphere electron transfer was probable with formation of a donor-acceptor complex.
      Further studies enabled the isolation and observation of intermediates by ESR and
      NMR spectroscopy. For anthracene, the immediate result of electron transfer, that
      is formation of an anthracene radical cation and reduced polyoxometalate, was
      observed by ESR spectroscopy. The ESR spectrum, together with kinetics
      experiments, including kinetic isotope experiments and (1)H NMR, support a Mars
      van Krevelen mechanism in which the rate-determining step is the oxygen-transfer
      reaction between the polyoxometalate and the intermediate radical cation.
      Anthraquinone is the only observable reaction product. For xanthene, the radical
      cation could not be observed. Instead, the initial radical cation undergoes fast
      additional proton and electron transfer (or hydrogen atom transfer) to yield a
      stable benzylic cation observable by (1)H NMR. Again, kinetics experiments
      support the notion of an oxygen-transfer rate-determining step between the
      xanthenyl cation and the polyoxometalate, with formation of xanthen-9-one as the
      only product. Schemes summarizing the proposed reaction mechanisms are presented.

PMID- 11525662
TI  - Octahedral coordination of halide ions (I-, Br-, Cl-) sandwich bonded with
      tridentate mercuracarborand-3 receptors.
AB  - The "anti-crown" B-hexamethyl 9-mercuracarborand-3 (1) was shown to complex
      halide ions (I-, Br-, Cl-) in an eta(3)-sandwich fashion. Symmetry-allowed
      interactions of the filled halide ion p-orbitals and the corresponding empty
      mercury p-orbitals result in three equivalent p(Hg)-p(halide)-p(Hg) three-center
      two-electron bonds and a sandwich structure. The molecular structures of
      [Li.(H(2)O)(4)][1(2).I].2CH(3)CN, MePPh(3)[1(2).Br].((CH(3))(2)CO)(2).(H(2)O)(2),
      and PPN[1(2).Cl] were determined by single-crystal X-ray diffraction studies.
      Compound [Li.(H(2)O)(4)][1(2).I].2CH(3)CN crystallized in the triclinic space
      group P-1, a = 13.312(8) A, b = 13.983(9) A, c = 13.996(9) A, alpha = 61.16(2)
      degrees, beta = 82.34(2) degrees, gamma = 86.58(2) degrees, V = 4365(2) A(3), Z =
      1, R = 0.063, and R(w) = 0.171. Compound
      MePPh(3)[1(2).Br].((CH(3))(2)CO)(2).(H(2)O)(2) crystallized in the monoclinic
      space group C2/c, a = 24.671(8) A, b = 17.576(6) A, c = 26.079(8) A, beta =
      106.424(6) degrees, V = 10847(6) A(3), Z = 8, R = 0.0607, and R(w) = 0.1506.
      Compound PPN[1(2).Cl] crystallized in the monoclinic space group C2/m, a =
      37.27(2) A, b = 29.25(1) A, c = 10.990(4) A, beta = 100.659(7) degrees, V =
      11774(8) A(3), Z = 4, R = 0.0911, and R(w) = 0.2369.

PMID- 11525663
TI  - Modeling the bacterial photosynthetic reaction center. 4. The structural,
      electrochemical, and hydrogen-bonding properties of 22 mutants of Rhodobacter
      sphaeroides.
AB  - Site-directed mutagenesis has been employed by a number of groups to produce
      mutants of bacterial photosynthetic reaction centers, with the aim of tuning
      their operation by modifying hydrogen-bond patterns in the close vicinity of the
      "special pair" of bacteriochlorophylls P identical with P(L)P(M). Direct X-ray
      structural measurements of the consequences of mutation are rare. Attention has
      mostly focused on effects on properties such as carbonyl stretching frequencies
      and midpoint potentials to infer indirectly the induced structural modifications.
      In this work, the structures of 22 mutants of Rhodobacter sphaeroides have been
      calculated using a mixed quantum-mechanical molecular-mechanical method by
      modifying the known structure of the wild type. We determine (i) the orientation
      of the 2a-acetyl groups in the wild type, FY(M197), and FH(M197) series mutants
      of the neutral and oxidized reaction center, (ii) the structure of the FY(M197)
      mutant and possible water penetration near the special pair, (iii) that
      significant protein chain distortions are required to assemble some M160 series
      mutants (LS(M160), LN(M160), LQ(M160), and LH(M160) are considered), (iv) that
      there is competition for hydrogen-bonding between the 9-keto and 10a-ester groups
      for the introduced histidine in LH(L131) mutants, (v) that the observed midpoint
      potential of P for HL(M202) heterodimer mutants, including one involving also
      LH(M160), can be correlated with the change of electrostatic potential
      experienced at P(L), (vi) that hydrogen-bond cleavage may sometimes be induced by
      oxidation of the special pair, (vii) that the OH group of tyrosine M210 points
      away from P(M), and (viii) that competitive hydrogen-bonding effects determine
      the change in properties of NL(L166) and NH(L166) mutants. A new technique is
      introduced for the determination of ionization energies at the Koopmans level
      from QM/MM calculations, and protein-induced Stark effects on vibrational
      frequencies are considered.

PMID- 11525664
TI  - Interaction of the substrate radical and the 5'-deoxyadenosine-5'-methyl group in
      vitamin B(12) coenzyme-dependent ethanolamine deaminase.
AB  - The distance and relative orientation of the C5' methyl group of 5'
      deoxyadenosine and the substrate radical in vitamin B(12) coenzyme-dependent
      ethanolamine deaminase from Salmonella typhimurium have been characterized by
      using X-band two-pulse electron spin-echo envelope modulation (ESEEM)
      spectroscopy in the disordered solid state. The (S)-2-aminopropanol-generated
      substrate radical catalytic intermediate was prepared by cryotrapping steady
      state mixtures of enzyme in which catalytically exchangeable hydrogen sites in
      the active site had been labeled by previous turnover on (2)H(4)-ethanolamine.
      Simulation of the time- and frequency-domain ESEEM requires two types of coupled
      (2)H. The strongly coupled (2)H has an effective dipole distance (r(eff)) of 2.2
      A, and isotropic coupling constant (A(iso)) of -0.35 MHz. The weakly coupled (2)H
      has r(eff) = 3.8 A and A(iso) = 0 MHz. The best (2)H ESEEM time- and frequency
      domain simulations are achieved with a model in which the hyperfine couplings
      arise from one strongly coupled hydrogen site and two equivalent weakly coupled
      hydrogen sites located on the C5' methyl group of 5'-deoxyadenosine. This model
      indicates that the unpaired electron on C1 of the substrate radical and C5' are
      separated by 3.2 A and are thus at closest contact. The close proximity of C1 and
      C5' indicates that C5' of the 5'-deoxyadenosyl moiety directly mediates radical
      migration between cobalt in cobalamin and the substrate/product site over a
      distance of 5-7 A in the active site of ethanolamine deaminase.

PMID- 11525665
TI  - Fullerometallic ion chemistry: reactions of C(60)Fe+ and C(20)H(10)Fe+ in the gas
      phase.
AB  - Fe+ has been attached to buckminsterfullerene, C(60), and corannulene,
      C(20)H(10), in the gas phase, and the reactivities of C(60)Fe+ and C(20)H(10)Fe+
      have been measured with several small inorganic and organic molecules in helium
      bath gas at 0.35 Torr using a selected-ion flow tube (SIFT) mass spectrometer.
      Comparisons with measured reactivities of the bare Fe+ ion indicate that the
      presence of C(60) and C(20)H(10) leads to enhancements in reactivity at room
      temperature of up to 5 orders of magnitude. Ligation was the only chemistry
      observed with D(2), N(2), CO(2), CH(4), C(2)H(2), C(2)H(4), SO(2), C(6)D(6),
      NH(3), H(2)O, and CO, but other channels were observed to compete with adduct
      formation in the reactions with N(2)O and O(2). The number of molecules
      sequentially ligated to the ion was different: up to five molecules of ligand
      added sequentially to Fe+, up to four molecules of ligand were observed to attach
      to C(60)Fe+, while only up to three molecules added to C(20)H(10)Fe+. C(60)+ and
      C(20)H(10)+ were observed to be unreactive toward the same ligands. The kinetic
      results show the influence of carbonaceous surfaces on metal ion reactivity and
      are interpreted in terms of the nature of the coordination of Fe+ to the
      carbonaceous surface. Catalytic effects of the carbonaceous surfaces were
      identified for the reactions with N(2)O and O(2).

PMID- 11525666
TI  - Paramagnetic cobalt(II) as an NMR probe of dendrimer structure: mobility and
      cooperativity of dendritic arms.
AB  - Cobalt(II) has been utilized as an external paramagnetic (1)H NMR probe for the
      study of the structure of dendrimers that possess specifically located metal
      recognition sites. The hyperfine-shifted (1)H NMR signals of the Co(II) complexes
      of several 2,6-diamidopyridine-containing dendrimers have been fully assigned by
      means of 1D and 2D NMR techniques, including NOE difference, EXSY, COSY, and
      TOCSY. Temperature-dependent T(1) values of the hyperfine-shifted signals were
      used to conclude that the Co(II)-dendrimer complexes are in the "liquidlike"
      regime, indicative of a shell-like structure instead of a "dense-core" structure.
      The presence of sizable cavities within the dendrimers was observed including a
      loosely packed conformation for the 2,6-diamidopyridino moiety to bind to
      potential guest molecules. Cooperativity among the dendritic arms in metal
      binding is also observed, whereby two dendritic arms bind to the metal center at
      the same time. In the case of dendrimers with the metal binding site located near
      the surface of the molecule, such binding cooperativity is still observed despite
      the large degree of freedom of the metal-binding moiety. Cooperativity among the
      dendritic arms can thus be considered an intrinsic property, which has to be
      taken into consideration in future design of functional dendrimers for the
      purpose of specific recognition and catalysis. The hydrodynamic radii of these
      dendrimers have been determined by means of nuclear Overhouser effect at low
      temperature. The study offers a method for the study of the dynamics of
      dendrimers in solution under different conditions and upon ligand binding and
      recognition. The study also provides a tool for monitoring systematic variation
      of the metal binding site in different dendrimer frameworks for specific
      applications, such as catalysis and molecular recognition.

PMID- 11525667
TI  - Total synthesis of the marine toxin polycavernoside A via selective
      macrolactonization of a trihydroxy carboxylic acid.

PMID- 11525668
TI  - The nitrous oxide complex, RuCl(2)(eta(1)-N(2)O)(P-N)(PPh(3)) (P-N =[o-(N,N
      dimethylamino)phenyl]diphenylphosphine); low temperature conversion of N(2)O to
      N(2) and O(2).

PMID- 11525669
TI  - Layered lithium iron nitride: a promising anode material for li-ion batteries.

PMID- 11525670
TI  - Cleavage of carbon-carbon triple bond of alkyne via hydroiminoacylation by Rh(I)
      catalyst.

PMID- 11525671
TI  - A unified approach to differentially linked beta-C-disaccharides by ring-closing
      metathesis.

PMID- 11525672
TI  - QM/MM studies show substantial tunneling for the hydrogen-transfer reaction in
      methylamine dehydrogenase.

PMID- 11525673
TI  - A strong preference for a salt-bridge structure in the gas phase: reactions of
      deprotonated amino acids with borane.

PMID- 11525674
TI  - Arsenate zeolite analogues with 11 topological types.

PMID- 11525675
TI  - A more stable configuration of HArF in solid argon.

PMID- 11525676
TI  - Highly enantioselective atom-transfer radical cyclization reactions catalyzed by
      chiral Lewis acids.

PMID- 11525677
TI  - Extreme zinc-binding thermodynamics of the metal sensor/regulator protein, ZntR.

PMID- 11525678
TI  - Detection of a conformational change in maltose binding protein by (129)Xe NMR
      spectroscopy.

PMID- 11525679
TI  - Nucleic acid template-directed assembly of metallosalen-DNA conjugates.

PMID- 11525681
TI  - Tri-tert-butylsilyl(triisopropylsilyl)silylene (tBu)(3)Si-Si-Si(iPr)(3) and
      chemical evidence for its reactions from a triplet electronic state.

PMID- 11525680
TI  - 34pi octaphyrin: first structural characterization of a planar, aromatic
      [1.0.1.0.1.0.1.0] octaphyrin with inverted heterocyclic rings.

PMID- 11525682
TI  - Preparing carbon nanotubes and nested fullerenes from supercritical CO(2) by a
      chemical reaction.

PMID- 11525683
TI  - Novel role of carbon monoxide as a Lewis acid catalyst for Friedel-Crafts
      reaction.

PMID- 11525684
TI  - Sensitive NMR detection of cationic-polymer-based gene delivery systems using
      saturation transfer via proton exchange.

PMID- 11525685
TI  - A miniature biofuel cell.

PMID- 11525686
TI  - Synthetic transformations of eleutherobin reveal new features of its microtubule
      stabilizing pharmacophore.

PMID- 11525687
TI  - Rapid identification of medium- to large-scale interdomain motion in modular
      proteins using dipolar couplings.

PMID- 11525688
TI  - Synthesis of oligonucleotides containing Fapy.dG (N6-(2-deoxy-alpha,beta-D
      erythro-pentofuranosyl)-2,6-diamino-4-hydroxy-5-formamidopyrimidine).

PMID- 11525689
TI  - Simulation of the spontaneous aggregation of phospholipids into bilayers.

PMID- 11525690
TI  - A new structure for the substrate-binding antibiotic ramoplanin.

PMID- 11525691
TI  - Accurate orientation of the functional groups of asparagine and glutamine side
      chains using one- and two-bond dipolar couplings.

PMID- 11525697
TI  - Timing of initial administration of low-molecular-weight heparin prophylaxis
      against deep vein thrombosis in patients following elective hip arthroplasty: a
      systematic review.
AB  - BACKGROUND: Perioperative and postoperative venous thrombosis are common in
      patients undergoing elective hip surgery. Prophylactic regimens include
      subcutaneous low-molecular-weight heparin 12 hours or more before or after
      surgery and oral anticoagulants. Recent clinical trials suggest that low
      molecular-weight heparin initiated in closer proximity to surgery is more
      effective than the present clinical practice. We performed a systematic review of
      the literature to assess the efficacy and safety of low-molecular-weight heparin
      administered at different times in relation to surgery vs oral anticoagulant
      prophylaxis. METHODS: Reviewers (A.F.M. and S.M.M.) identified studies by
      searching MEDLINE, reviewing references from retrieved articles, scanning
      abstracts from conference proceedings, and contacting investigators and
      pharmaceutical companies. Randomized trials comparing low-molecular-weight
      heparin administered at different times relative to surgery with oral
      anticoagulants in patients undergoing elective hip arthroplasty, evaluated using
      contrast phlebography, were selected. Two reviewers (A.F.M. and S.M.M.) extracted
      data independently. RESULTS: The literature review identified 4 randomized trials
      meeting predefined inclusion criteria. The results indicate that low-molecular
      weight heparin initiated in close proximity to surgery resulted in absolute risk
      reductions of 11% to 13% for deep vein thrombosis, corresponding to relative risk
      reductions of 43% to 55% compared with oral anticoagulants. Low-molecular-weight
      heparin initiated 12 hours before surgery or 12 to 24 hours postoperatively was
      not more effective than oral anticoagulants. Low-molecular-weight heparin
      initiated postoperatively in close proximity to surgery at half the usual dose
      was not associated with a clinically or statistically significant increase in
      major bleeding rates (P =.16). CONCLUSIONS: The timing of initiating low
      molecular-weight heparin significantly influences antithrombotic effectiveness.
      The practice of delayed initiation of low-molecular-weight heparin prophylaxis
      results in suboptimal antithrombotic effectiveness without a substantive safety
      advantage.

PMID- 11525698
TI  - Limited patient adherence to highly active antiretroviral therapy for HIV-1
      infection in an observational cohort study.
AB  - BACKGROUND: Adherence to highly active antiretroviral therapy (HAART) for human
      immunodeficiency syndrome type 1 (HIV-1) infection is essential to sustain viral
      suppression and prevent drug resistance. We investigated adherence to HAART among
      patients in a clinical cohort study. METHODS: Patients receiving HAART had their
      plasma concentrations of protease inhibitors or nevirapine measured and completed
      a questionnaire on adherence. We determined the percentage of patients who
      reported taking all antiretroviral medication on time and according to dietary
      instructions in the past week. Drug exposure was compared between patients
      reporting deviation from their regimen and fully adherent patients. Among
      patients who received HAART for at least 24 weeks, we assessed the association
      between adherence and virologic outcome. RESULTS: A total of 224 of 261 eligible
      patients completed a questionnaire. Forty-seven percent reported taking all
      antiretroviral medication on time and according to dietary instructions. Patients
      who reported deviation from their regimen showed lower drug exposure compared
      with fully adherent patients (median concentration ratio, 0.81 vs 1.07; P =.001).
      Among those receiving HAART for at least 24 weeks, patients reporting deviation
      from their regimen were less likely to have plasma HIV-1 RNA levels below 500
      copies/mL (adjusted odds ratio, 4.0; 95% confidence interval, 1.4-11.6) compared
      with fully adherent patients. CONCLUSIONS: Only half of the patients took all
      antiretroviral medication in accordance with time and dietary instructions in the
      preceding week. Deviation from the antiretroviral regimen was associated with
      decreased drug exposure and a decreased likelihood of having suppressed plasma
      HIV-1 RNA loads. Patient adherence should remain a prime concern in the
      management of HIV-1 infection.

PMID- 11525699
TI  - Headache evaluation and treatment by primary care physicians in an emergency
      department in the era of triptans.
AB  - BACKGROUND: Despite advances in treatment, patients with migraine have been
      underdiagnosed and undertreated. METHODS: Documentation of visits by patients
      with headache to an urgent care department staffed by primary care physicians was
      reviewed. Patients were also sent a brief headache screen, and those who replied
      were interviewed by telephone. "Repeaters" (patients who made 3 or more visits in
      6 months) were excluded from chart review. RESULTS: Over 6 months, 518 patients
      made 1004 visits to the emergency department for primary headache complaints: 464
      patients (90%) made 1 or 2 visits (total visits, 502). A review of 174 charts
      documenting a diagnosis of migraine found that (1) the need for prophylaxis was
      determined in only 40 (31%) of the patients who were not already undergoing
      prophylaxis and (2) treatment in the emergency department was migraine specific
      in 46 patients (26%) or otherwise appropriate in 45 (25%). A review of 90 charts
      documenting nonmigraine diagnoses found that 30 patients (33%) had adequate
      history documented to exclude migraine as the diagnosis. Eighty-six patients
      (17%) were interviewed. An emergency department diagnosis of migraine (n = 59)
      corresponded to a final diagnosis of migraine with (n = 21) or without (n = 18)
      medication overuse or chronic daily headache and/or transformed migraine with (n
      = 18) or without (n = 2) medication overuse. Discharge diagnoses that were not
      migraine (n = 27) had final diagnoses of migraine with (n = 9) or without (n = 9)
      medication overuse or chronic daily headache/transformed migraine with (n = 7) or
      without (n = 2) medication overuse. CONCLUSIONS: In this emergency department
      population, many patients with migraine, chronic daily headache, or medication
      overuse are not accurately diagnosed. The need for prophylaxis is not usually
      assessed. Treatment is migraine specific in the minority of patients. Tension
      type headache is rarely an accurate diagnosis in this emergency department
      population.

PMID- 11525700
TI  - Unsaid but not forgotten: patients' unvoiced desires in office visits.
AB  - OBJECTIVES: To examine patient, physician, and health care system characteristics
      associated with unvoiced desires for action, as well as the consequences of these
      unspoken requests. PATIENTS AND METHODS: Patient surveys were administered
      before, immediately after, and 2 weeks after outpatient visits in the practices
      of 45 family practice, internal medicine, and cardiology physicians working in a
      multispecialty group practice or group model health maintenance organization.
      Data were collected at the index visit from 909 patients, of whom 97.6% were
      surveyed 2 weeks after the outpatient visit. Before the visit, patients rated
      their trust in the physician, health concerns, and health status. After the
      visit, patients reported on various types of unexpressed desires and rated their
      visit satisfaction. At follow-up, patients rated their satisfaction, health
      concerns, and health status, and also described their postvisit health care use.
      Evaluations of the visit were also obtained from physicians. RESULTS:
      Approximately 9% of the patients had 1 or more unvoiced desire(s). Desires for
      referrals (16.5% of desiring patients) and physical therapy (8.2%) were least
      likely to be communicated. Patients with unexpressed desires tended to be young,
      undereducated, and unmarried and were less likely to trust their physician.
      Patients with unvoiced desires evaluated the physician and visit less positively;
      these encounters were evaluated by physicians as requiring more effort. Holding
      an unvoiced desire was associated with less symptom improvement, but did not
      affect postvisit health care use. CONCLUSIONS: Patients' unvoiced needs affect
      patients' and physicians' visit evaluations and patients' subjective perceptions
      of improvement. Implications of these findings for clinical practice are
      examined.

PMID- 11525702
TI  - Oral contraceptive use and hormone replacement therapy are associated with
      microalbuminuria.
AB  - BACKGROUND: Controversy exists regarding the adverse and beneficial effects of
      oral contraceptive use and hormone replacement therapy. Microalbuminuria is
      associated with increased risk of renal and cardiovascular disease. OBJECTIVE: To
      examine the association between oral contraceptive use or hormone replacement
      therapy and microalbuminuria. METHODS: We performed a case-control study of the
      baseline data and historical pharmacy data of 4301 female subjects of the
      Prevention of Renal and Vascular End Stage Disease study cohort, aged 28 to 75
      years, excluding women who were pregnant or had type 1 diabetes mellitus. The
      main outcome measure was microalbuminuria, defined as a urinary albumin excretion
      of 30 to 300 mg per 24 hours (recorded as the mean of two 24-hour urine
      collections). RESULTS: After adjusting for age, hypertension, diabetes, obesity,
      hyperlipidemia, and smoking, the odds ratio (OR) for having microalbuminuria was
      1.90 (95% confidence interval [CI], 1.23-2.93) for premenopausal oral
      contraceptive users and 2.05 (95% CI, 1.12-3.77) for postmenopausal hormone
      replacement therapy users. The point estimate increased in a dose-dependent
      fashion, albeit insignificantly, according to the estrogen content of the oral
      contraceptives (<30 microg ethinyl estradiol: OR, 1.11; 95% CI, 0.14-8.56; 30 to
      <50 microg: OR, 1.83; 95% CI, 1.17-2.87; and 50 microg: OR, 2.72; 95% CI, 0.81
      9.08). The OR was greater in oral contraceptives with a second-generation (OR,
      2.04; 95% CI, 1.28-3.25) vs a third-generation progestin (OR, 1.39; 95% CI, 0.63
      3.06). The OR increased with the duration of hormone replacement therapy (< or =5
      years, OR, 1.28; 95% CI, 0.37-4.50; >5 years, OR, 2.56; 95% CI, 1.32-4.97).
      CONCLUSION: Regular and long-term oral contraceptive use and hormone replacement
      therapy are associated with an increased risk for microalbuminuria and
      cardiovascular disease.

PMID- 11525701
TI  - Prevalence of gastrointestinal symptoms associated with diabetes mellitus: a
      population-based survey of 15,000 adults.
AB  - BACKGROUND: Gastrointestinal symptoms are reportedly common in diabetes, but a
      causal link is controversial and adequate population control data are lacking.
      OBJECTIVE: To determine whether gastrointestinal symptoms are more frequent in
      persons with diabetes, particularly in those with poor glycemic control. METHODS:
      Fifteen thousand adults were mailed a questionnaire (response rate, 60.0%)
      containing validated questions on the frequency of troublesome gastrointestinal
      symptoms within the past 3 months, diabetic status, and self-reported glycemic
      control. The prevalence of 16 symptoms and 5 symptom complexes, reported to occur
      often or very often, was compared using logistic regression analysis, adjusting
      for age and sex. RESULTS: Overall, 8657 eligible subjects responded; 423 (4.9%)
      reported having diabetes. Most (94.8%) had type 2 diabetes mellitus. Adjusting
      for age and sex, all 16 symptoms and the 5 symptom complexes were significantly
      more frequent in subjects with diabetes compared with controls. An increased
      prevalence rate of symptoms was significantly associated with poorer levels of
      glycemic control but not with duration of diabetes or type of diabetic treatment.
      CONCLUSIONS: Diabetes mellitus is associated with an increased prevalence of
      upper and lower gastrointestinal symptoms. This effect may be linked to poor
      glycemic control but not to duration of diabetes or type of treatment.

PMID- 11525703
TI  - Hyperthermia after cardiac arrest is associated with an unfavorable neurologic
      outcome.
AB  - BACKGROUND: Moderate elevation of brain temperature, when present during or after
      ischemia, may markedly worsen the resulting injury. OBJECTIVE: To evaluate the
      impact of body temperature on neurologic outcome after successful cardiopulmonary
      resuscitation. METHODS: In patients who experienced a witnessed cardiac arrest of
      presumed cardiac cause, the temperature was recorded on admission to the
      emergency department and after 2, 4, 6, 12, 18, 24, 36, and 48 hours. The lowest
      temperature within 4 hours and the highest temperature during the first 48 hours
      after restoration of spontaneous circulation were recorded and correlated to the
      best-achieved cerebral performance categories' score within 6 months. RESULTS:
      Over 43 months, of 698 patients, 151 were included. The median age was 60 years
      (interquartile range, 53-69 years); the estimated median no-flow duration was 5
      minutes (interquartile range, 0-10 minutes), and the estimated median low-flow
      duration was 14.5 minutes (interquartile range, 3-25 minutes). Forty-two patients
      (28%) underwent bystander-administered basic life support. Within 6 months, 74
      patients (49%) had a favorable functional neurologic recovery, and a total of 86
      patients (57%) survived until 6 months after the event. The temperature on
      admission showed no statistically significant difference (P =.39). Patients with
      a favorable neurologic recovery showed a higher lowest temperature within 4 hours
      (35.8 degrees C [35.0 degrees C-36.1 degrees C] vs 35.2 degrees C [34.5 degrees C
      35.7 degrees C]; P =.002) and a lower highest temperature during the first 48
      hours after restoration of spontaneous circulation (37.7 degrees C [36.9 degrees
      C-38.6 degrees C] vs 38.3 degrees C [37.8 degrees C-38.9 degrees C]; P<.001)
      (data are given as the median [interquartile range]). For each degree Celsius
      higher than 37 degrees C, the risk of an unfavorable neurologic recovery
      increases, with an odds ratio of 2.26 (95% confidence interval, 1.24-4.12).
      CONCLUSION: Hyperthermia is a potential factor for an unfavorable functional
      neurologic recovery after successful cardiopulmonary resuscitation.

PMID- 11525704
TI  - A first-tier rapid assay for the serodiagnosis of Borrelia burgdorferi infection.
AB  - BACKGROUND: The present recommendation for the serologic diagnosis of Lyme
      disease is a 2-tier process in which a serum sample with a positive or equivocal
      result by an enzyme-linked immunosorbent assay (ELISA) or immunofluorescent assay
      is then followed by supplemental testing by Western blot. Our laboratory has
      developed recombinant chimeric proteins composed of key Borrelia epitopes. These
      novel antigens are consistent and are easily standardized. METHODS: We adapted
      these recombinant proteins into a new immunochromatographic format that can be
      used as a highly sensitive and specific first-tier assay that can be used to
      replace the ELISA or immunofluorescent assay. RESULTS: This rapid test was
      equally sensitive (P>.05) and more specific (P<.05) than a frequently used
      commercial whole cell ELISA. The overall clinical accuracy achieved on agreement
      studies among 3 Lyme research laboratories on clinically defined serum panels was
      shown to be statistically equivalent to the commercial ELISA. The assay can
      detect anti-Borrelia burgdorferi antibodies in either serum or whole blood.
      CONCLUSION: This sensitive and specific rapid assay, which is suited for the
      physician's office, streamlines the 2-tier system by allowing the physician to
      determine if a Western blot is necessary at the time of the initial office visit.

PMID- 11525705
TI  - Risk of cataract in patients treated with statins.
AB  - BACKGROUND: Studies in dogs showed that some hydroxymethylglutaryl coenzyme A
      reductase inhibitors (statins) are associated with cataract when administered in
      excessive doses. Clinical safety data of statins regarding cataract development
      in humans have been of limited value so far. OBJECTIVE: To determine whether long
      term use of statins is associated with an increased risk of cataract. METHODS: We
      conducted a case-control analysis using data from the United Kingdom-based
      General Practice Research Database. The main outcome was a first-time diagnosis
      of cataract and/or cataract extraction in patients aged 40 to 79 years. Controls
      were matched to cases on age, sex, practice, calendar time, and duration of
      medical history in the database. Use of statins, fibrates, or other lipid
      lowering drugs was compared with nonuse of any lipid-lowering drug, stratified by
      exposure duration and dose. RESULTS: We identified 7405 cases and 28 327
      controls. Long-term use of statins (eg, > or =30 prescriptions) was not
      associated with an increased cataract risk (adjusted odds ratio [OR], 0.9; 95%
      confidence interval [CI], 0.5-1.6), nor was use of fibrates or of other lipid
      lowering drugs (adjusted OR, 0.5; 95% CI, 0.3-1.1; and OR, 0.7; 95% CI, 0.1-5.6,
      respectively). We found evidence that concomitant use of simvastatin and
      erythromycin, a potent inhibitor of simvastatin metabolism, is associated with an
      increased cataract risk (adjusted odds ratio, 2.2; 95% confidence interval, 1.2
      4.1). CONCLUSIONS: Our study provides evidence that long-term use of therapeutic
      statin doses does not increase the risk of developing cataract. Concomitant use
      of erythromycin and simvastatin may increase the cataract risk.

PMID- 11525706
TI  - A randomized multicenter trial of crotalinae polyvalent immune Fab (ovine)
      antivenom for the treatment for crotaline snakebite in the United States.
AB  - BACKGROUND: Current therapy for crotaline snakebite includes antivenin
      (Crotalidae) polyvalent, an antivenom with numerous adverse effects. We compared
      the efficacy and safety of 2 dosing regimens with a new antivenom, Crotalinae
      polyvalent immune Fab (Fab AV). METHODS: A single dose of Fab AV alone (as-needed
      [PRN] group) was compared with an initial dose plus repeated treatments during 18
      hours (scheduled group) in a multicenter randomized trial. The study included
      patients with minimal or moderate envenomation by a crotaline snake within the
      preceding 6 hours, aged 10 years or older, in whom worsening of the envenomation
      syndrome was observed before Fab AV treatment. After treatment with Fab AV to
      achieve initial control, patients were randomized to the scheduled or PRN
      treatment group. Scheduled group patients received additional doses of Fab AV
      every 6 hours for 3 doses. The PRN group received no planned additional doses of
      antivenom. RESULTS: The mean severity score of the 31 patients decreased from
      4.35 to 2.39 points (P<.001); there was no difference between scheduled and PRN
      groups. No patient in the scheduled group received unplanned Fab AV doses, but 8
      of 16 patients in the PRN group received unplanned doses (P =.002). Acute
      reactions occurred in 6 patients (19%), and serum sickness occurred in 6 (23%) of
      26 patients who returned for follow-up. CONCLUSIONS: In the first randomized
      trial of antivenom in the United States, Fab AV effectively terminated venom
      effects. Since the unplanned use of Fab AV in the PRN group was common, the
      treatment regimen may require more than 1 initial dose.

PMID- 11525707
TI  - Practice guidelines: useful and "participative" method? Survey of Italian
      physicians by professional setting.
AB  - BACKGROUND: Professional setting might be a key determinant of physicians'
      attitudes toward practice guidelines, influencing the effect of their
      implementation. Because no previous surveys have specifically considered this
      aspect, we evaluated the perceived role and usefulness of guidelines, as well as
      barriers to and facilitators of their implementation, for hospital, primary care,
      and nonpracticing clinicians. METHODS: A 43-item self-administered questionnaire
      was sent to all National Health Service physicians in the province of Modena,
      Italy (593 primary care physicians, 1049 hospital physicians, and 149
      nonpracticing clinicians), and 1199 (66.9%) responded. Opinions and attitudes
      were assessed using 5-point ordinal scales and an attitude measurement scale.
      Results were evaluated overall and by professional setting, sex, age, year of
      graduation, and academic background. RESULTS: Practice guidelines were generally
      perceived to be less useful than other sources of medical information (eg,
      personal experience, conferences, colleagues, articles, the Internet, and
      textbooks [pharmaceutical representatives were the exception]). Most physicians
      thought that guidelines are developed for cost-containment reasons and expressed
      concerns about their limited applicability to individual patients and local
      settings. Most respondents did not favor the involvement of health professionals
      other than physicians in guideline development and use and preferred nonmonetary
      incentives for their implementation. Answers to individual items and attitude
      scores varied significantly across professional settings. Primary care physicians
      showed, in general, the least favorable attitudes toward practice guidelines,
      toward nonphysicians participating in guideline development and use, and toward
      incentives for guideline users. CONCLUSIONS: Physicians perceived practice
      guidelines as externally imposed and cost-containment tools rather than as
      decision-supporting tools. Regularly monitoring attitudes toward practice
      guidelines can be helpful to evaluate potential barriers to their adoption.

PMID- 11525708
TI  - Subcutaneous nodules after a cat bite.

PMID- 11525709
TI  - Lung abscess as a complication of steroid treatment in pemphigus vulgaris.

PMID- 11525710
TI  - Underrepresentation of the risk and incidence of anaphylaxis to foods.

PMID- 11525712
TI  - Early discharge of infected patients through appropriate antibiotic use: a
      response.

PMID- 11525714
TI  - Interaction between angiotensin-converting enzyme inhibitors and aspirin.

PMID- 11525716
TI  - Introduction of D-dimer assay: does it increase resource utilization or correct
      identification of pulmonary embolism?

PMID- 11525718
TI  - America's health care follies.

PMID- 11525717
TI  - In care of patients.

PMID- 11525719
TI  - Workshop report: identification of research needs breast cancer etiology.
AB  - A workshop to evaluate the scientific evidence for the etiologic associations
      between modifiable lifestyle and environmental risk factors and to identify areas
      for future research in breast cancer etiology was sponsored jointly by the
      Canadian Breast Cancer Initiative and the Canadian Breast Cancer Research
      Initiative in May, 2001. Reviews of the scientific evidence in these topics were
      commissioned and an expert panel convened to consider the reviews and make
      recommendations for research. The panel concluded that there was substantial
      evidence to proceed with additional research in several areas of breast cancer
      etiology. Particular support for future research for several lifestyle and
      environmental risk factors including alcohol, diet, physical activity,
      anthropometric factors, hormonally active agents and occupational exposures was
      identified. Several emerging hypotheses for breast cancer etiology were also
      considered and recommendations made in these areas. Specific areas for future
      consideration included: insulin-like growth factors, pharmaceuticals, viruses,
      psychosocial factors, and functional polymorphisms. The panel also identified
      common themes for future research including: studies of exposures across the life
      cycle; research in populations with unusual exposure levels; consideration of
      effect modification; development of improved exposure assessment methods and use
      of intermediate endpoints; separation of disease subtypes by hormone receptor
      status, stage and tumour markers; and consideration of biological mechanisms in
      breast cancer etiology.

PMID- 11525720
TI  - Assessing the surveillance capability of Canada's national health surveys.
AB  - We assessed Canada's national health surveys as surveillance instruments, with
      emphasis on comparing the temporal structure of data sets with those generated by
      the US Behavioral Risk Factor Surveillance System (BRFSS). Only the Canadian
      Tobacco Use Monitoring Survey (CTUMS) has the BRFSS capability to generate
      continuous, uniform time series with monthly intervals. These time series can
      offer substantial extra value for retrospective analysis such as program
      evaluation in addition to surveillance. Expanding CTUMS is a simple option for
      providing an ongoing, uniform monthly survey instrument for non-tobacco
      variables. The Canadian Community Health Survey (CCHS) will generate monthly
      data, and could potentially generate useful continuous time series even though
      surveys at the health region and provincial levels will alternate annually.
      Reconfiguring the CCHS, or even implementing a provincial surveillance survey
      based on the BRFSS model are other viable options, but each option has associated
      tradeoffs or obstacles.

PMID- 11525721
TI  - Completeness and accuracy of the birth registry data on congenital anomalies in
      Alberta, Canada.
AB  - Vital statistics and other administrative data are becoming an increasingly
      important source for epidemiologic research and surveillance. This study, the
      first in Canada, evaluated the usefulness of birth registry data on congenital
      anomalies in Alberta. We compared the number of birth defects recorded in the
      birth registry with the number collected through the Alberta Congenital Anomalies
      Surveillance System (ACASS) between 1985 and 1996. In addition, records of 3,881
      (99.9 %) babies with (a) birth defect(s) from the ACASS during 1994--1996 were
      matched to the birth registry by deterministic linkage. Of these, 2,969 babies
      had single anomalies that were used for validity analysis. The anomalies were
      grouped by those within International Classification of Disease (ICD) ICD-9
      Section XIV (ICD-9=740.0-759.9) and those outside the Section XIV. For those
      within Section XIV, 24 summary diagnostic categories were examined. As shown, the
      total case count from the birth registry was on average about 3 % lower than that
      from the ACASS between 1985 and 1996. The validity of diagnostic categories is
      high for the 24 categories examined, with an overall agreement of between 80 %
      and 100 %. The sensitivity, positive predictive value, and kappa are also high
      for all these anomalies combined during 1994 and 1996, showing 95.7 %, 99.8, and
      0.81 respectively.

PMID- 11525722
TI  - The development of the National Diabetes Surveillance System (NDSS) in Canada.

PMID- 11525724
TI  - Life, sex, and WT1 isoforms--three amino acids can make all the difference.

PMID- 11525725
TI  - Intracellular cycling of lysosomal enzyme receptors: cytoplasmic tails' tales.

PMID- 11525726
TI  - Doublesex surprises.

PMID- 11525727
TI  - Emerging themes in lipid rafts and caveolae.

PMID- 11525728
TI  - Mechanism of processivity clamp opening by the delta subunit wrench of the clamp
      loader complex of E. coli DNA polymerase III.
AB  - The dimeric ring-shaped sliding clamp of E. coli DNA polymerase III (beta
      subunit, homolog of eukaryotic PCNA) is loaded onto DNA by the clamp loader gamma
      complex (homolog of eukaryotic Replication Factor C, RFC). The delta subunit of
      the gamma complex binds to the beta ring and opens it. The crystal structure of a
      beta:delta complex shows that delta, which is structurally related to the delta'
      and gamma subunits of the gamma complex, is a molecular wrench that induces or
      traps a conformational change in beta such that one of its dimer interfaces is
      destabilized. Structural comparisons and molecular dynamics simulations suggest a
      spring-loaded mechanism in which the beta ring opens spontaneously once a dimer
      interface is perturbed by the delta wrench.

PMID- 11525729
TI  - Crystal structure of the processivity clamp loader gamma (gamma) complex of E.
      coli DNA polymerase III.
AB  - The gamma complex, an AAA+ ATPase, is the bacterial homolog of eukaryotic
      replication factor C (RFC) that loads the sliding clamp (beta, homologous to
      PCNA) onto DNA. The 2.7/3.0 A crystal structure of gamma complex reveals a
      pentameric arrangement of subunits, with stoichiometry delta':gamma(3):delta. The
      C-terminal domains of the subunits form a circular collar that supports an
      asymmetric arrangement of the N-terminal ATP binding domains of the gamma motor
      and the structurally related domains of the delta' stator and the delta wrench.
      The structure suggests a mechanism by which the gamma complex switches between a
      closed state, in which the beta-interacting element of delta is hidden by delta',
      and an open form similar to the crystal structure, in which delta is free to bind
      to beta.

PMID- 11525730
TI  - Isolation and characterization of sigma(70)-retaining transcription elongation
      complexes from Escherichia coli.
AB  - sigma(70) subunit is thought to be released from the core RNA polymerase (RNAP)
      upon the transition from initiation to elongation or shortly afterward. Here, we
      identify a population of RNAP from E. coli that retains sigma(70) throughout
      elongation. The relative amount of this population appears to depend on cellular
      growth and reaches its maximum during the stationary phase. The proportion of
      sigma(70)-retaining elongation complexes (EC-sigma(70)) is invariant with various
      promoters or distances from the transcription start site. EC-sigma(70) responds
      to pauses, intrinsic terminators, and the elongation factor NusA similarly to EC
      without sigma(70). However, EC-sigma(70) has a substantially higher ability to
      support multiple rounds of transcription at certain promoters, suggesting its
      profound role in gene expression and regulation in bacteria.

PMID- 11525731
TI  - Translocation of sigma(70) with RNA polymerase during transcription: fluorescence
      resonance energy transfer assay for movement relative to DNA.
AB  - Using fluorescence resonance energy transfer, we show that, in the majority of
      transcription complexes, sigma(70) is not released from RNA polymerase upon
      transition from initiation to elongation, but, instead, remains associated with
      RNA polymerase and translocates with RNA polymerase. The results argue against
      the presumption that there are necessary subunit-composition differences, and
      corresponding necessary mechanistic differences, in initiation and elongation.
      The methods of this report should be generalizable to monitor movement of any
      molecule relative to any nucleic acid.

PMID- 11525732
TI  - The fate of dsRNA in the nucleus: a p54(nrb)-containing complex mediates the
      nuclear retention of promiscuously A-to-I edited RNAs.
AB  - How do cells discriminate between selectively edited mRNAs that encode new
      protein isoforms, and dsRNA-induced, promiscuously edited RNAs that encode
      nonfunctional, mutant proteins? We have developed a Xenopus oocyte model system
      which shows that a variety of hyperedited, inosine-containing RNAs are
      specifically retained in the nucleus. To uncover the mechanism of inosine-induced
      retention, HeLa cell nuclear extracts were used to isolate a multiprotein complex
      that binds specifically and cooperatively to inosine-containing RNAs. This
      complex contains the inosine-specific RNA binding protein p54(nrb), the splicing
      factor PSF, and the inner nuclear matrix structural protein matrin 3. We provide
      evidence that one function of the complex identified here is to anchor
      hyperedited RNAs to the nuclear matrix, while allowing selectively edited mRNAs
      to be exported.

PMID- 11525733
TI  - An mRNA cap binding protein, ABH1, modulates early abscisic acid signal
      transduction in Arabidopsis.
AB  - The plant hormone abscisic acid (ABA) regulates important stress and
      developmental responses. We have isolated a recessive ABA hypersensitive mutant,
      abh1, that shows hormone specificity to ABA. ABH1 encodes the Arabidopsis homolog
      of a nuclear mRNA cap binding protein and functions in a heterodimeric complex to
      bind the mRNA cap structure. DNA chip analyses show that only a few transcripts
      are down-regulated in abh1, several of which are implicated in ABA signaling.
      Consistent with these results, abh1 plants show ABA-hypersensitive stomatal
      closing and reduced wilting during drought. Interestingly, ABA-hypersensitive
      cytosolic calcium increases in abh1 guard cells demonstrate amplification of
      early ABA signaling. Thus, ABH1 represents a modulator of ABA signaling proposed
      to function by transcript alteration of early ABA signaling elements.

PMID- 11525734
TI  - Integrin-mediated activation of Cdc42 controls cell polarity in migrating
      astrocytes through PKCzeta.
AB  - We describe here a signal transduction pathway controlling the establishment of
      mammalian cell polarity. Scratching a confluent monolayer of primary rat
      astrocytes leads to polarization of cells at the leading edge. The microtubule
      organizing center, the microtubule cytoskeleton, and the Golgi reorganize to face
      the new free space, and directed cell protrusion and migration specifically occur
      perpendicularly to the scratch. We show here that the interaction of integrins
      with extracellular matrix at the newly formed cell front leads to the activation
      and polarized recruitment of Cdc42, which in turn recruits and activates a
      cytoplasmic mPar6/PKCzeta complex. Localized PKCzeta activity, acting through the
      microtubule motor protein dynein, is required for all aspects of induced polarity
      in these cells.

PMID- 11525735
TI  - Chromogranin A, an "on/off" switch controlling dense-core secretory granule
      biogenesis.
AB  - We present evidence that regulation of dense-core secretory granule biogenesis
      and hormone secretion in endocrine cells is dependent on chromogranin A (CGA).
      Downregulation of CGA expression in a neuroendocrine cell line, PC12, by
      antisense RNAs led to profound loss of dense-core secretory granules, impairment
      of regulated secretion of a transfected prohormone, and reduction of secretory
      granule proteins. Transfection of bovine CGA into a CGA-deficient PC12 clone
      rescued the regulated secretory phenotype. Stable transfection of CGA into a CGA
      deficient pituitary cell line, 6T3, lacking a regulated secretory pathway,
      restored regulated secretion. Overexpression of CGA induced dense-core granules,
      immunoreactive for CGA, in nonendocrine fibroblast CV-1 cells. We conclude that
      CGA is an "on/off" switch that alone is sufficient to drive dense-core secretory
      granule biogenesis and hormone sequestration in endocrine cells.

PMID- 11525736
TI  - Drosophila neuroblasts sequentially express transcription factors which specify
      the temporal identity of their neuronal progeny.
AB  - Neural precursors often generate distinct cell types in a specific order, but the
      intrinsic or extrinsic cues regulating the timing of cell fate specification are
      poorly understood. Here we show that Drosophila neural precursors (neuroblasts)
      sequentially express the transcription factors Hunchback --> Kruppel --> Pdm -->
      Castor, with differentiated progeny maintaining the transcription factor profile
      present at their birth. Hunchback is necessary and sufficient for first-born cell
      fates, whereas Kruppel is necessary and sufficient for second-born cell fates;
      this is observed in multiple lineages and is independent of the cell type
      involved. We propose that Hunchback and Kruppel control early-born temporal
      identity in neuroblast cell lineages.

PMID- 11525737
TI  - Multiple regimes of constrained chromosome motion are regulated in the interphase
      Drosophila nucleus.
AB  - BACKGROUND: Increasing evidence indicates specific changes in the three
      dimensional organization of chromosomes in the cell nucleus during the cell cycle
      and development. These changes may be linked to changes in both the coordinated
      regulation of gene transcription and the timing of chromosome replication. While
      there is cytological evidence for short-range diffusive motion of chromosomes
      during interphase, the mechanisms for large-scale chromosome remodeling inside
      the nucleus remain unknown. RESULTS: Chromosome motion was tracked in Drosophila
      spermatocyte nuclei by 3D fluorescence microscopy. The Lac repressor/lac operator
      system was used to label specific chromosomal sites in live tissues, allowing
      extended observation of chromatin motion in different cell cycle stages. Our
      results reveal a highly dynamic chromosome organization governed by two types of
      motion: a fast, short-range component over a 1-2 s time scale and a slower
      component related to long-range chromosome motion within the nucleus. The motion
      patterns are consistent with a random walk. In early G2, short-range motion
      occurs within a small, approximately 0.5 microm radius domain, while long-range
      motion is confined to a much larger, chromosome-sized domain. Progression through
      G2 as cells approach meiotic prophase is accompanied by a complete arrest of long
      range chromosome motion. CONCLUSIONS: Our analysis provides direct evidence for
      cell cycle-regulated changes in interphase chromatin motion. These changes are
      consistent with changes in local and long-range constraints on chromosome
      motility. We propose that dynamic interactions between chromosomes and internal
      nuclear structures modulate the range and rate of interphase chromatin diffusion
      and thereby regulate large-scale nuclear chromosome organization.

PMID- 11525738
TI  - Altering telomere structure allows telomerase to act in yeast lacking ATM
      kinases.
AB  - BACKGROUND: Telomerase is a ribonucleoprotein that copies a short RNA template
      into telomeric DNA, maintaining eukaryotic chromosome ends and preventing
      replicative senescence. Telomeres differentiate chromosome ends from DNA double
      stranded breaks. Nevertheless, the DNA damage-responsive ATM kinases Tel1p and
      Mec1p are required for normal telomere maintenance in Saccharomyces cerevisiae.
      We tested whether the ATM kinases are required for telomerase enzyme activity or
      whether it is their action on the telomere that allows telomeric DNA synthesis.
      RESULTS: Cells lacking Tel1p and Mec1p had wild-type levels of telomerase
      activity in vitro. Furthermore, altering telomere structure in three different
      ways showed that telomerase can function in ATM kinase-deleted cells: tel1 mec1
      cells senesced more slowly than tel1 mec1 cells that also lacked TLC1, which
      encodes telomerase RNA, suggesting that tel1 mec1 cells have residual telomerase
      function; deleting the telomere-associated proteins Rif1p and Rif2p in tel1 mec1
      cells prevented senescence; we isolated a point mutation in the telomerase RNA
      template domain (tlc1-476A) that altered telomeric DNA sequences, causing
      uncontrolled telomeric DNA elongation and increasing single strandedness. In tel1
      mec1 cells, tlc1-476A telomerase was also capable of uncontrolled synthesis, but
      only after telomeres had shortened for >30 generations. CONCLUSION: Our results
      show that, without Tel1p and Mec1p, telomerase is still active and can act in
      vivo when the telomere structure is disrupted by various means. Hence, a primary
      function of the ATM-family kinases in telomere maintenance is to act on the
      substrate of telomerase, the telomere, rather than to activate the enzymatic
      activity of telomerase.

PMID- 11525739
TI  - Establishment of polarity in lateral organs of plants.
AB  - BACKGROUND: Asymmetric development of plant lateral organs initiates by
      partitioning of organ primordia into distinct domains along their adaxial/abaxial
      axis. A recent model proposes that a meristem-born signal, acting in a
      concentration-dependent manner, differentially activates PHABULOSA-like genes,
      which in turn suppress abaxial-promoting factors. As yet, no abaxial factors have
      been identified that when compromised give rise to adaxialized organs. RESULTS:
      Single mutants in either of the closely related genes KANADI1 (KAN1) or KANADI2
      (KAN2) have little or no effect on plant morphology. However, in kan1 kan2 double
      mutant plants, there is a replacement of abaxial cell types by adaxial ones in
      most lateral organs. The alterations in polarity establishment are associated
      with expansion in the expression domain of the PHB-like genes and reduction in
      the expression of the previously described abaxial-promoting YABBY genes. Ectopic
      expression of either of the KANADI genes throughout leaf primordia results in
      dramatic transformation of adaxial cell types into abaxial ones, failure of
      lateral blade expansion, and vascular tissue formation. CONCLUSION: The
      phenotypes of KANADI loss- and gain-of-function alleles suggest that fine
      regulation of these genes is at the core of polarity establishment. As such, they
      are likely to be targets of the PHB-mediated meristem-born signaling that
      patterns lateral organ primordia. PHB-like genes and the abaxial-promoting KANADI
      and YABBY genes appear to be expressed throughout primordia anlagen before
      becoming confined to their corresponding domains as primordia arise. This
      suggests that the establishment of polarity in plant lateral organs occurs via
      mutual repression interactions between ab/ad factors after primordium emergence,
      consistent with the results of classical dissection experiments.

PMID- 11525740
TI  - Single-cell internalization during zebrafish gastrulation.
AB  - During gastrulation, germ layers are formed as prospective mesodermal and
      endodermal cells internalize and come to underlie the ectoderm [1-9]. Despite the
      pivotal role of gastrulation in animal development, the cellular interactions
      underlying this process are poorly understood. In zebrafish, mesoderm and
      endoderm formation requires the Nodal signals Cyclops and Squint and their
      cofactor One-eyed pinhead (Oep) [10-14]. We found that marginal cells in maternal
      zygotic oep (MZoep) mutants do not internalize during gastrulation and acquire
      neural and tail fates at the expense of head and trunk mesendoderm. The lack of
      internalization in MZoep embryos and the cell-autonomous requirement for oep in
      Nodal signaling enabled us to test whether internalization can be achieved by
      individual cells or whether it depends on interactions within a group of cells.
      We found that individual MZoep mutant cells transplanted to the margin of wild
      type blastula embryos initially internalize with their neighbors but are unable
      to contribute to the mesendoderm. In the reciprocal experiment, single wild-type
      cells transplanted to the margin of MZoep mutant embryos autonomously internalize
      and can express the mesendodermal markers axial/foxA2 and sox17. These results
      suggest that internalization and mesendoderm formation in zebrafish can be
      attained autonomously by single cells.

PMID- 11525741
TI  - MAPK specificity in the yeast pheromone response independent of transcriptional
      activation.
AB  - The mechanisms whereby different external cues stimulate the same mitogen
      activated protein kinase (MAPK) cascade, yet trigger an appropriately distinct
      biological response, epitomize the conundrum of specificity in cell signaling. In
      yeast, shared upstream components of the mating pheromone and filamentous growth
      pathways activate two related MAPKs, Fus3 and Kss1, which in turn regulate
      programs of gene expression via the transcription factor Ste12. As fus3, but not
      kss1, strains are impaired for mating, Fus3 exhibits specificity for the
      pheromone response. To account for this specificity, it has been suggested that
      Fus3 physically occludes Kss1 from pheromone-activated signaling complexes, which
      are formed on the scaffold protein Ste5. However, we find that genome-wide
      expression profiles of pheromone-treated wild-type, fus3, and kss1 deletion
      strains are highly correlated for all induced genes and, further, that two
      catalytically inactive versions of Fus3 fail to abrogate the pheromone-induced
      transcriptional response. Consistently, Fus3 and Kss1 kinase activity is induced
      to an equivalent extent in pheromone-treated cells. In contrast, both in vivo and
      in an in vitro-reconstituted MAPK system, Fus3, but not Kss1, exhibits strong
      substrate selectivity toward Far1, a bifunctional protein required for
      polarization and G(1) arrest. This effect accounts for the failure to repress
      G(1)-S specific transcription in fus3 strains and, in part, explains the mating
      defect of such strains. MAPK specificity in the pheromone response evidently
      occurs primarily at the substrate level, as opposed to specific kinase activation
      by dedicated signaling complexes.

PMID- 11525742
TI  - Cooperative action of antioxidant defense systems in Drosophila.
AB  - Molecular oxygen is key to aerobic life but is also converted into cytotoxic
      byproducts referred to as reactive oxygen species (ROS). Intracellular defense
      systems that protect cells from ROS-induced damage include glutathione reductase
      (GR), thioredoxin reductase (TrxR), superoxide dismutase (Sod), and catalase
      (Cat). Sod and Cat constitute an evolutionary conserved ROS defense system
      against superoxide; Sod converts superoxide anions to H(2)O(2), and Cat prevents
      free hydroxyl radical formation by breaking down H(2)O(2) into oxygen and water.
      As a consequence, they are important effectors in the life span determination of
      the fly Drosophila. ROS defense by TrxR and GR is more indirect. They transfer
      reducing equivalents from NADPH to thioredoxin (Trx) and glutathione disulfide
      (GSSG), respectively, resulting in Trx(SH)(2) and glutathione (GSH), which act as
      effective intracellular antioxidants. TrxR and GR were found to be molecularly
      conserved. However, the single GR homolog of Drosophila specifies TrxR activity,
      which compensates for the absence of a true GR system for recycling GSH. We show
      that TrxR null mutations reduce the capacity to adequately protect cells from
      cytotoxic damage, resulting in larval death, whereas mutations causing reduced
      TrxR activity affect pupal eclosion and cause a severe reduction of the adult
      life span. We also provide genetic evidence for a functional interaction between
      TrxR, Sod1, and Cat, indicating that the burden of ROS metabolism in Drosophila
      is shared by the two defense systems.

PMID- 11525743
TI  - Activation of JNK1 contributes to dystrophic muscle pathogenesis.
AB  - Duchenne Muscular Dystrophy (DMD) originates from deleterious mutations in the
      dystrophin gene, with a complete loss of the protein product. Subsequently, the
      disease is manifested in severe striated muscle wasting and death in early
      adulthood. Dystrophin provides a structural base for the assembly of an integral
      membrane protein complex. As such, dystrophin deficiency leads to an altered
      mechanical integrity of the myofiber and a predisposition to contraction-induced
      damage. However, the development of myofiber degeneration prior to an observed
      mechanical defect has been documented in various dystrophic models. Although
      activation of a detrimental signal transduction pathway has been suggested as a
      probable cause, a specific cellular cascade has yet to be defined. Here, it is
      shown that murine models of DMD displayed a muscle-specific activation of JNK1.
      Independent activation of JNK1 resulted in defects in myotube viability and
      integrity in vitro, similar to a dystrophic phenotype. In addition, direct muscle
      injection of an adenoviral construct containing the JNK1 inhibitory protein,
      JIP1, dramatically attenuated the progression of dystrophic myofiber destruction.
      Taken together, these results suggest that a JNK1-mediated signal cascade is a
      conserved feature of dystrophic muscle and contributes to the progression of the
      disease pathogenesis.

PMID- 11525744
TI  - Critical role for glycosphingolipids in Niemann-Pick disease type C.
AB  - Niemann-Pick type C (NPC) disease is a cholesterol lipidosis caused by mutations
      in NPC1 and NPC2 gene loci. Most human cases are caused by defects in NPC1, as
      are the spontaneously occurring NPC diseases in mice and cats. NPC1 protein
      possesses a sterol-sensing domain and has been localized to vesicles that are
      believed to facilitate the recycling of unesterified cholesterol from late
      endosomes/lysosomes to the ER and Golgi. In addition to accumulating cholesterol,
      NPC1-deficient cells also accumulate gangliosides and other glycosphingolipids
      (GSLs), and neuropathological abnormalities in NPC disease closely resemble those
      seen in primary gangliosidoses. These findings led us to hypothesize that NPC1
      may also function in GSL homeostasis. To evaluate this possibility, we treated
      murine and feline NPC models with N-butyldeoxynojirimycin (NB-DNJ), an inhibitor
      of glucosylceramide synthase, a pivotal enzyme in the early GSL synthetic
      pathway. Treated animals showed delayed onset of neurological dysfunction,
      increased average life span (in mice), and reduced ganglioside accumulation and
      accompanying neuropathological changes. These results are consistent with our
      hypothesis and with GSLs being centrally involved in the pathogenesis of NPC
      disease, and they suggest that drugs inhibiting GSL synthesis could have a
      similar ameliorating effect on the human disorder.

PMID- 11525745
TI  - Compartmentalization of beta-secretase (Asp2) into low-buoyant density,
      noncaveolar lipid rafts.
AB  - Recent epidemiological studies show a reduced prevalence of Alzheimer's disease
      (AD) in patients treated with inhibitors of cholesterol biosynthesis. Moreover,
      the cholesterol-transport protein, apolipoprotein E4, and elevated cholesterol
      are important risk factors for AD. Additionally, in vitro and in vivo studies
      show that intracellular cholesterol levels can modulate the processing of amyloid
      precursor protein (APP) to beta-amyloid, the major constituent of senile plaques.
      Cholesterol plays a crucial role in maintaining lipid rafts in a functional
      state. Lipid rafts are cholesterol-enriched membrane microdomains implicated in
      signal transduction, protein trafficking, and proteolytic processing. Since APP,
      beta-amyloid, and the putative gamma-secretase, presenilin-1 (PS-1), have all
      been found in lipid rafts, we hypothesized that the recently identified beta
      secretase, Asp2 (BACE1), might also be present in rafts. Here, we report that
      recombinant Asp2 expressed in three distinct cell lines is raft associated. Using
      both detergent and nondetergent methods, Asp2 protein and activity were found in
      a light membrane raft fraction that also contained other components of the
      amyloidogenic pathway. Immunoisolation of caveolin-containing vesicles indicated
      that Asp2 was present in a unique raft population distinct from caveolae.
      Finally, depletion of raft cholesterol abrogated association of Asp2 with the
      light membrane fraction. These observations are consistent with the raft
      localization of APP processing and suggest that the partitioning of Asp2 into
      lipid rafts may underlie the cholesterol sensitivity of beta-amyloid production.

PMID- 11525746
TI  - A natural variability in the proline-rich motif of Nef modulates HIV-1
      replication in primary T cells.
AB  - In the infected host, the Nef protein of HIV/SIV is required for high viral loads
      and thus disease progression. Recent evidence indicates that Nef enhances
      replication in the T cell compartment after the virus is transmitted from
      dendritic cells (DC). The underlying mechanism, however, is not clear. Here, we
      report that a natural variability in the proline-rich motif (R71T) profoundly
      modulated Nef-stimulated viral replication in primary T cells of immature
      dendritic cell/T cell cocultures. Whereas both Nef variants (R/T-Nef)
      downregulated CD4, only the isoform supporting viral replication (R-Nef)
      efficiently interacted with signaling molecules of the T cell receptor (TCR)
      environment and stimulated cellular activation. Structural analysis suggested
      that the R to T conversion induces conformational changes, altering the
      flexibility of the loop containing the PxxP motif and hence its ability to bind
      cellular partners. Our report suggests that functionally and conformationally
      distinct Nef isoforms modulate HIV replication on the interaction level with the
      TCR-signaling environment once the virus enters the T cell compartment.

PMID- 11525748
TI  - Johns Hopkins troubles raise trial questions.

PMID- 11525747
TI  - Inhibition of the Arp2/3 complex-nucleated actin polymerization and branch
      formation by tropomyosin.
AB  - The actin filament network immediately under the plasma membrane at the leading
      edge of rapidly moving cells consists of short, branched filaments, while those
      deeper in the cortex are much longer and are rarely branched. Nucleation by the
      Arp2/3 complex activated by membrane-bound factors (Rho-family GTPases and
      PIP(2)) is postulated to account for the formation of the branched network.
      Tropomyosin (TM) binds along the sides of filaments and protects them from
      severing proteins and pointed-end depolymerization in vitro. Here, we show that
      TM inhibits actin filament branching and nucleation by the Arp2/3 complex
      activated by WASp-WA. Tropomyosin increases the lag at the outset of
      polymerization, reduces the concentration of ends by 75%, and reduces the number
      of branches by approximately 50%. We conclude that TM bound to actin filaments
      inhibits their ability to act as secondary activators of nucleation by the Arp2/3
      complex. This is the first example of inhibition of branching by an actin binding
      protein. We suggest that TM suppresses the nucleation of actin filament branches
      from actin filaments in the deep cortex of motile cells. Other abundant actin
      binding proteins may also locally regulate the branching nucleation by the Arp2/3
      complex in cells.

PMID- 11525749
TI  - Balancing interests in autism study.

PMID- 11525751
TI  - Why bother with nectar?

PMID- 11525752
TI  - Filopodia.

PMID- 11525753
TI  - The lateral geniculate nucleus.

PMID- 11525754
TI  - Wingless signalling: more about the Wingless morphogen.
AB  - Recent work on pattern formation in the Drosophila embryo reveals a new mechanism
      which shapes the gradient of the secreted morphogen, Wingless: Wingless protein
      is degraded more rapidly on one side of its source than on the other.

PMID- 11525755
TI  - Neural processing: the logic of multiplication in single neurons.
AB  - Theory indicates that neural networks can derive considerable computational power
      from a simple multiplication of their inputs, but the extent to which real
      neurons do this is unclear. A recent study of the auditory localization pathway
      of the barn owl has shed new light on this important question.

PMID- 11525756
TI  - Protein stability: the COP9 signalosome gets in on the act.
AB  - The COP9 signalosome is a multiprotein complex somewhat similar to the lid
      component of the 26S proteasome. Recent studies suggest that it regulates the
      stability of proteins by interfering with the ubiquitin-proteasome pathway via
      deneddylation and phosphorylation.

PMID- 11525757
TI  - Cortical plasticity: learning while you sleep?
AB  - Sleep has been suggested to facilitate memory consolidation or learning, but
      there has been little direct evidence of a link between synaptic plasticity and
      sleep. A recent study suggests a role for sleep in the plastic changes that the
      visual cortex undergoes in response to occlusion of one eye early in life.

PMID- 11525758
TI  - Photoperiodism: the consistent use of CONSTANS.
AB  - Photoperiodic induction of flowering in the long-day plant Arabidopsis is
      mediated by the circadian regulated CONSTANS gene. New evidence suggests that
      CONSTANS-like genes have a similar role in short-day induction of flowering of
      rice and Pharbitis.

PMID- 11525759
TI  - Morphogen gradients: nodal enters the stage.
AB  - Morphogen gradients are proposed to organise cell fates during development via
      the long-range activity of secreted molecules. Their existence in vertebrates,
      however, has been debated. A recent study has identified the Nodal-related
      protein Squint as a bona fide morphogen in vertebrate mesoderm.

PMID- 11525760
TI  - Peroxisomes: the extended shuttle to the peroxisome matrix.
AB  - A recent study indicates that protein import into the peroxisomal matrix occurs
      by a possibly unique mechanism involving the shuttling of cargo receptors into
      and out of the organelles.

PMID- 11525761
TI  - Face recognition: when a nod is better than a wink.
AB  - A recent study has shown that, when people talk, their changing facial
      expressions and head movements provide dynamic cues for recognition.

PMID- 11525762
TI  - RNA world: catalysis abets binding, but not vice versa.
AB  - The recent selection of a complex ribozyme capable of general polymerization on a
      template in trans has revealed how catalysts may have arisen from one another in
      the RNA world.

PMID- 11525763
TI  - New complexities for BRCA1 and BRCA2.
AB  - A large number of diverse functions have been attributed to the BRCA1 and BRCA2
      breast cancer susceptibility genes. Here we review recent progress in the field.

PMID- 11525764
TI  - Pharmacological action of melatonin in shock, inflammation and
      ischemia/reperfusion injury.
AB  - A vast amount of circumstantial evidence implicates oxygen-derived free radicals
      (especially, superoxide and hydroxyl radical) and high-energy oxidants (such as
      peroxynitrite) as mediators of inflammation, shock and ischemia/reperfusion
      injury. The aim of this review is to describe recent developments in the field of
      oxidative stress research. The first part of the review focuses on the roles of
      reactive oxygen species in shock, inflammation and ischemia/reperfusion injury.
      The second part of the review described the pharmacological action of melatonin
      in shock, ischemia/reperfusion, and inflammation. The role of reactive oxygen
      species: Immunohistochemical and biochemical evidence demonstrate the production
      of reactive oxygen species in shock, inflammation and ischemia/reperfusion
      injury. Reactive oxygen species can initiate a wide range of toxic oxidative
      reactions. These include the initiation of lipid peroxidation, direct inhibition
      of mitochondrial respiratory chain enzymes, inactivation of glyceraldehyde-3
      phosphate dehydrogenase, inhibition of membrane sodium/potassium ATP-ase
      activity, inactivation of membrane sodium channels, and other oxidative
      modifications of proteins. All these toxicities are likely to play a role in the
      pathophysiology of shock, inflammation and ischemia and reperfusion. Treatment
      with melatonin has been shown to prevent in vivo the delayed vascular
      decompensation and the cellular energetic failure associated with shock,
      inflammation and ischemia/reperfusion injury. Reactive oxygen species (e.g.,
      superoxide, peroxynitrite, hydroxyl radical and hydrogen peroxide) are all
      potential reactants capable of initiating DNA single-strand breakage, with
      subsequent activation of the nuclear enzyme poly (ADP-ribose) synthetase (PARS),
      leading to eventual severe energy depletion of the cells, and necrotic-type cell
      death. Recently, it has been demonstrated that melatonin inhibits the activation
      of poly (ADP-ribose) synthetase, and prevents the organ injury associated with
      shock, inflammation and ischemia and reperfusion.

PMID- 11525765
TI  - Interaction between cyclic GMP protein kinase and cyclic AMP may be diminished in
      stunned cardiac myocytes.
AB  - We tested the hypothesis that the importance of the negative functional effects
      of the cyclic GMP protein kinase would be reduced in stunned (simulated
      ischemia/reperfusion) cardiac myocytes. Ventricular cardiac myocytes were
      isolated from New Zealand white rabbits (N=7). Myocytes were studied at baseline
      and after simulated ischemia (15 min of 95% N(2)-5% CO(2) at 37 degrees C)
      followed by simulated reperfusion (reoxygenation). Cell shortening was studied
      with a video edge detector; O(2) consumption was measured using O(2) electrodes.
      Protein phosphorylation was measured autoradiographically after gel
      electrophoresis. Functional and metabolic data were acquired after: (1) 8-(4
      chlorophenylthio)guanosine-3',5'-monophosphate (PCPT, cGMP protein kinase
      agonist) 10(-7) or 10(-5) M; (2) 8-Br-cAMP 10(-5) M followed by PCPT 10(-7) or
      10(-5) M; (3) beta-phenyl-1, N(2)-etheno-8-bromoguanosine-3',5'
      monophosphorothioate, SP-isomer (SP, cGMP protein kinase agonist) 10(-7) or 10(
      5) M; (2) 8-Br-cAMP 10(-5) M followed by SP 10(-7) or 10(-5) M. At baseline,
      percent of shortening (Pcs) and maximal rate of shortening (Rs) were
      significantly lower in the stunned myocytes (Pcs: 5.0+/-0.2% control vs. 3.8+/
      0.3 stunned; Rs: 64.8+/-5.9 microm/s control vs. 46.9+/-4.8 stunned). In both
      groups, PCPT and SP dose-dependently decreased Pcs and Rs. The effects were
      slightly, but not significantly, less in stunned myocytes. 8-Br-cyclic AMP
      significantly increased function in control, but not stunned myocytes (Pcs, 4.5+/
      0.5 to 6.2+/-0.8 control vs. 3.1+/-0.2 to 3.6+/-0.2 stunned). The negative
      functional effects of PCPT and SP were diminished after 8-Br-cyclic AMP in
      control (from -39% to-29%) and diminished significantly more in the stunned
      myocytes (-19%). PCPT and cyclic AMP phosphorylated similar protein bands. In
      stunned myocytes, three (22, 31 and 53 kDa) bands were enhanced less by PCPT.

PMID- 11525766
TI  - Prostaglandin E(2) increases surfactant secretion via the EP(1) receptor in rat
      alveolar type II cells.
AB  - Prostaglandin E(2), the predominant cyclooxygenase metabolite of arachidonic acid
      in alveolar type II cells, can stimulate pulmonary surfactant secretion. The
      actions of prostaglandin E(2) are mediated by four prostaglandin E (EP) receptor
      subtypes designated EP(1), EP(2), EP(3) and EP(4). These subtypes couple to
      different signal transduction pathways. However, it is not clear which of these
      subtypes is expressed on type II cells and mediates surfactant secretion. We
      found that the four subtypes of EP receptors are expressed on the primary
      cultured alveolar type II cells from adult rats. We also concluded that EP(1)
      receptor appears to mediate prostaglandin E(2)-induced surfactant secretion
      through Ca(2+) mobilization.

PMID- 11525767
TI  - Effects of kappa-opioid receptor agonists on long-term cocaine use and dopamine
      neurotransmission.
AB  - kappa-Opioid receptor agonists have been suggested as treatments for cocaine
      addiction based on studies showing that they block cocaine-related behaviors. To
      determine the effects of kappa-opioid receptor agonists on long-term behavioral
      effects associated with cocaine and the neurochemical bases underlying these
      effects, rats were treated with the selective kappa-opioid receptor agonist U
      69593 ((+)(5alpha,7alpha,8beta)-N-methyl-N-[7-(1-pyrrolidinyl)-1 oxaspiro[4.5]dec
      8-yl]-benzeneacetamide) alone or in combination with cocaine and locomotor
      activity was measured daily. In addition, dopamine transporter and dopamine
      receptor densities were measured using autoradiographic techniques, and tyrosine
      hydroxylase was measured using immunoautoradiographic techniques. Treatment with
      U-69593 with or without cocaine decreased locomotor activity. When challenged
      with cocaine after a 5-day treatment period, the effects of cocaine were markedly
      reduced in rats initially treated with U-69593 compared to vehicle. When U-69593
      was administered five times with 3-day intervals, it alone had no effect on
      locomotor activity but still reduced activity associated with a cocaine
      injection. After five daily injections, U-69593 decreased dopamine transporter
      and dopamine D(2) receptor densities and increased tyrosine hydroxylase levels.
      These changes were not seen after the 3-day interval regimen, even though cocaine
      induced activity was greatly reduced. These findings show that the effects
      associated with daily U-69593 treatment are attenuated if the drug is
      administered with a greater interval, while maintaining a blockade of cocaine
      induced activity. In addition, U-69593 can block cocaine-induced locomotor
      effects without major perturbation of the dopamine system.

PMID- 11525768
TI  - Neuroprotection afforded by NAAG and NAALADase inhibition requires glial cells
      and metabotropic glutamate receptor activation.
AB  - N-acetylated-alpha-linked-acidic-dipeptidase (NAALADase or glutamate
      carboxypeptidase II) cleaves the neuropeptide N-acetyl-aspartyl-glutamate (NAAG)
      to glutamate and N-acetyl-aspartate (NAA). Previously, NAAG and 2
      (phosphonomethyl)-pentanedioic acid (2-PMPA), a potent and selective NAALADase
      inhibitor, were found to be neuroprotective in neuronal/glial co-cultures and in
      animals following transient middle cerebral artery occlusion. In this report, we
      examined the involvement of glial cells and metabotropic glutamate (mGlu)
      receptors in neuroprotection mediated by NAAG and 2-PMPA in an in vitro model of
      metabolic inhibition. Neuroprotection of neuronal/glial co-cultures by both NAAG
      and 2-PMPA, against metabolic inhibition, was significantly higher than
      neuroprotection in the absence of glia. Similarly, (2S,2'R,3'R)-2-(2',3'
      dicarboxycyclopropyl)glycine (DCG IV), a selective group II mGlu receptor
      agonist, was less neuroprotective in the absence of glia. Selective group II mGlu
      receptor antagonists and (S)-alpha-methyl-4-carboxyphenylglycine (MCPG), a non
      selective mGlu receptor antagonist, reduced the protection afforded by both NAAG
      and 2-PMPA when using neuronal/glial co-cultures. In contrast, groups I and III
      mGlu receptor antagonists did not affect NAAG or 2-PMPA neuroprotection. These
      results underscore the critical involvement of glia and group II mGlu receptors
      in NAAG and 2-PMPA-mediated neuroprotection.

PMID- 11525769
TI  - Participation of the nitric oxide-cyclic GMP-ATP-sensitive K(+) channel pathway
      in the antinociceptive action of ketorolac.
AB  - The involvement of nitric oxide (NO), cyclic GMP and ATP-sensitive K(+) channels
      in the antinociceptive effect of ketorolac was assessed using the formalin test
      in the rat. Local administration of ketorolac in a formalin-injured paw produced
      a dose-dependent antinociceptive effect due to a local action, as drug
      administration in the contralateral paw was ineffective. Pretreatment of the
      injured paw with N(G)-L-nitro-arginine methyl ester (L-NAME, an NO synthesis
      inhibitor), 1H-(1,2,4)-oxadiazolo(4,2-a)quinoxalin-1-one (ODQ, a soluble guanylyl
      cyclase inhibitor) or glibenclamide (an ATP-sensitive K(+) channel blocker)
      prevented ketorolac-induced antinociception. However, pretreatment with saline or
      N(G)-D-nitro-arginine methyl ester (D-NAME) did not block antinociception. Local
      administration of S-nitroso-N-acetylpenicillamine (SNAP, an NO donor) was
      inactive by itself, but increased the effect of ketorolac. The present results
      suggest that the antinociceptive effect of ketorolac involves activation of the
      NO-cyclic GMP pathway, followed by an opening of ATP-sensitive K(+) channels at
      the peripheral level.

PMID- 11525770
TI  - Influence of benzodiazepine binding site ligands on fear-conditioned contextual
      memory.
AB  - Eight compounds that bind to the benzodiazepine binding site on the gamma-amino
      butyric acid(A) (GABA(A)) receptor were assessed for their influence on
      contextual memory, an aspect of memory affected in various cognitive disorders
      including Alzheimer's disease. Using a Pavlovian fear-conditioning paradigm, each
      ligand was evaluated in C57Bl/6 mice in regards to its direct affect on
      contextual memory and whether the ligand could attenuate scopolamine-induced
      contextual memory impairment. Of the eight ligands tested, one impaired
      contextual memory (agonist), six attenuated scopolamine-induced contextual memory
      impairment (inverse agonists), and one antagonized the ability of an inverse
      agonist to attenuate scopolamine-induced contextual memory impairment. Hence,
      further demonstrating the bi-directional influence benzodiazepine binding site
      ligands are able to exert on memory modulation. This study serves as an initial
      starting point in the development of pharmacological tools to be used in
      deciphering how GABA(A) receptors influence contextual memory.

PMID- 11525771
TI  - Differential patterns of performance impairment result from changed reinforcer
      efficacy or distracting stimulation in a two-choice rodent spatial signal
      detection task.
AB  - Measures of the discriminabililty of stimuli in signal detection tasks can be
      influenced by alterations of motivational state. In the present study, rats
      performed an operant signal detection procedure that required the completion of a
      fixed number of responses before a stimulus was presented at one of two front cue
      lamps to separately measure the motivation to respond from the ability to respond
      accurately. One manipulation, presession water access, affected the speed and
      frequency that trials were initiated, but did not affect response accuracy. In
      contrast, a flashing houselight during the session, and i.p. ((5R,10S)-(+)-5
      methyl-10,11-dihydro-5H-dibenzo[a,d,] cyclohepten-5,10-imine (dizocilpine or MK
      801), a glutamate N-methyl-D-aspartate receptor antagonist, impaired response
      accuracy in a stimulus duration-dependent manner. These results suggest that it
      is possible to procedurally isolate the motivation to respond to stimuli from
      accuracy of detection, and thereby protect attending from side effects of drugs
      that influence the motivation to respond.

PMID- 11525772
TI  - Effects of lithium chloride on induction and expression of methylphenidate
      sensitization.
AB  - Repeated administration of psychomotor stimulants produces an enduring and
      progressively enhanced behavioral response known as behavioral sensitization,
      which has been implicated as a model for psychiatric disorders such as mania,
      schizophrenia, and drug addiction. The objective of the study was to determine
      whether lithium chloride (LiCl), an anti-manic agent, is effective in blocking
      the development and/or the expression of behavioral sensitization to
      methylphenidate. Male Sprague-Dawley rats (n=64) weighing 170-190 g were randomly
      divided into seven treatment groups. A computerized animal activity monitor
      system continuously recorded locomotor activity for 16 days. Effects of LiCl on
      induction of methylphenidate sensitization were studied by giving LiCl before or
      during six daily methylphenidate administrations. Effects of LiCl on the
      expression of methylphenidate sensitization were studied by injecting LiCl after
      sensitization to methylphenidate was induced. It was shown that LiCl treatment
      modulated the acute methylphenidate effects by transiently attenuating the
      locomotor response to methylphenidate during the six daily methylphenidate
      administrations but neither single nor multiple treatments with LiCl blocked the
      development or the expression of behavioral sensitization.

PMID- 11525773
TI  - A novel neurotensin analog blocks cocaine- and D-amphetamine-induced
      hyperactivity.
AB  - Neurotensin is a tridecapeptide that exhibits selective anatomic and
      neurochemical interactions with dopaminergic systems. Since dopaminergic
      neurotransmission underlies many of the behavioral properties of
      psychostimulants, and since neurotensin has been implicated in modulating
      dopaminergic neurotransmitter systems, we tested the effect of our novel
      neurotensin analog, NT69L (N-methyl-Arg(8),L-Lys(9),L-neo-Trp(11),tert
      Leu(12)]neurotensin-(8-13)), on hyperactivity caused by cocaine and D
      amphetamine. Previously, we showed that NT69L reduces body temperature, blocks
      apomorphine-induced climbing, and haloperidol-induced catalepsy. In this study,
      NT69L blocked the hyperactivity induced by both cocaine and D-amphetamine
      administered at three different doses each, when this peptide was injected
      intraperitoneally. These results provide further evidence for the involvement of
      the neurotensin system in some of the behavioral properties of psychostimulants
      and suggest that NT69L may find clinical application in patients who abuse this
      class of compounds.

PMID- 11525774
TI  - LY354740 attenuates the expression of long-term behavioral sensitization induced
      by a single session of foot shocks.
AB  - Exposure of rats to a single session of foot shocks sensitizes behavioral
      responses to novel stimuli. There is evidence that metabotropic glutamate (mGlu)
      receptors play a role in sensitization processes. In the present study, we
      investigated the role of mGlu(2/3) receptors in the long-term (14 days) increase
      in defensive withdrawal behavior after a single session of foot shocks. Exposure
      to foot shocks increased defensive withdrawal behavior. The mGlu(2/3) receptor
      agonist LY354740 ((1S,2S,5R,6S)-(+)-2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylic
      acid, 0.1 mg/kg, i.p.) normalized the increased latency and the decreased time in
      the light of the preshocked rats. We conclude that activation of mGlu(2/3)
      receptors attenuates the foot shock-induced expression of behavioral
      sensitization.

PMID- 11525775
TI  - Intravenous (+)-methamphetamine causes complex dose-dependent physiologic changes
      in awake rats.
AB  - Hemodynamic and temperature dose-response relationships were characterized in
      freely moving rats following i.v. (+)-methamphetamine administration to mimic the
      rapid onset of effects experienced by many human users. Rats received saline and
      (+)-methamphetamine in a repeated-measures, mixed-sequence design at 22+/-1
      degrees C. Significantly greater blood pressure and heart rate elevations were
      observed after 1.0 and 3.0 mg/kg (+)-methamphetamine vs. 0.1 and 0.3 mg/kg. The
      time to peak hemodynamic values and the duration of effects were significantly
      greater after 3.0 mg/kg vs. the lower doses. The time to peak temperatures was
      significantly longer after 1.0 mg/kg vs. the lower doses. Following 3.0 mg/kg,
      all rats experienced temperature decreases before having elevated temperatures.
      The duration and magnitude of the delayed temperature elevations were
      significantly greater after 3.0 mg/kg vs. the lower doses. In conclusion, the (+)
      methamphetamine-induced hemodynamic and temperature effects were not temporally
      synchronized, and the complex responses were not linearly related to dose.

PMID- 11525776
TI  - Differential effects of prostacyclin and iloprost in the isolated carotid artery
      of the guinea-pig.
AB  - The effects on membrane potential of prostacyclin and iloprost were compared in
      smooth muscle cells of the guinea pig carotid artery. Both prostacyclin and
      iloprost induced hyperpolarization of the smooth muscle cells. In the presence of
      (3R)-3-(4-fluorophenyl-sulfonamido)-1,2,3,4-tetrahydro-9-carbazolepropanoic acid
      (Bay U3405), an antagonist of TP receptors, the response to iloprost was
      unaffected while that to prostacyclin was increased. Iloprost-induced
      hyperpolarizations were abolished by glibenclamide while those to prostacyclin
      were either not affected, or converted to either depolarization or to rhythmic
      electrical activity. The latter effects of prostacyclin were abolished by Bay
      U3405. After removal of the endothelium, iloprost and prostacyclin produced
      hyperpolarizations similar to those observed in control blood vessels. However,
      in the presence of glibenclamide, prostacyclin produced only depolarizations
      inhibited by Bay U3405. These results suggest that iloprost activates IP
      receptors and K(ATP) channels in smooth muscle. In contrast, prostacyclin
      produces additional endothelium-dependent and -independent effects via activation
      of TP receptors.

PMID- 11525777
TI  - Cyclooxygenase selectivity of non-steroid anti-inflammatory drugs in humans: ex
      vivo evaluation.
AB  - We have recently described a novel assay to assess ex vivo the activity and
      selectivity on cyclooxygenase-1 and -2 (EC 1.14.99.1) of non-steroid anti
      inflammatory drugs (NSAID) administered to rats [Br. J. Pharmacol. 126 (1999)
      1824.]. Here, we have extended these studies to humans. Healthy male volunteers
      were given orally one of the following drugs (mg) for 5 days: etodolac (200 or
      400 b.i.d.), meloxicam (7.5 or 15 q.d.), nimesulide (100 or 200 b.i.d.),
      nabumetone (500 or 1000 b.i.d.) or naproxen (500 b.i.d.). Blood samples were
      withdrawn from the volunteers before and up to 24 h after the last dose. Plasma
      obtained from the blood was tested for its ability to inhibit prostanoid
      formation in interleukin-1beta-treated A549 cells (cyclooxygenase-2 system) and
      human washed platelets (cyclooxygenase-1 system). Plasma from etodolac-treated
      subjects demonstrated a slight selectivity towards the inhibition of
      cyclooxygenase-2. This effect was more prominent in plasma from subjects
      receiving meloxicam or nimesulide. Plasma from nabumetone-treated subjects showed
      no or little selectivity towards cyclooxygenase-1 depending on the dose of drug
      administered, while plasma taken from subjects receiving naproxen was more active
      at inhibiting cyclooxygenase-1 than cyclooxygenase-2. In conclusion, we have
      demonstrated that this assay can be used to assess ex vivo the relative activity
      against cyclooxygenase-1 and cyclooxygenase-2 of NSAIDs consumed by human
      volunteers. It is to be hoped that data from such systems will aid in our
      understanding of the relationships between the differential inhibition of
      cyclooxygenase-1 and cyclooxygenase-2 by NSAIDs and their reported efficacies and
      (gastrointestinal) toxicities.

PMID- 11525778
TI  - Pharmacodynamic analysis of steroid 5alpha-reductase inhibitory actions of Z-350
      in rat prostate.
AB  - The pharmacodynamics of (S)-4-[3-[4-[1-(4-methylphenyl)-3-[4-(2
      methoxyphenyl)piperazine-1-yl]propoxy]benzoyl]indole-1-yl] butyric acid
      hydrochloride (Z-350), which has alpha(1)-adrenoceptor antagonistic and steroid
      5alpha-reductase inhibitory effects, were investigated in rats. The disposition
      of Z-350 was a function of linear kinetics at doses from 1 to 30 mg/kg; the
      bioavailability was calculated to be 65.2%. The inhibition of 5alpha-reductase
      was dependent on the concentration of Z-350 in plasma and in the prostate.
      Analysis of the relationship between the concentration in the prostate and the
      inhibition seen after a single oral administration showed that the Hill constant
      was almost 1.0 and EC(50)(n(H)) was 47.4 ng/g of tissue; these parameters did not
      change after multiple administration. Z-350 inhibited 5alpha-reductase 1 h after
      oral administration at a dose of 3 mg/kg; maximum inhibition was observed after 2
      4 h, and the inhibition (%) was maintained for 24 h after oral administration.

PMID- 11525779
TI  - Modulation of airway remodeling-associated mediators by the antifibrotic
      compound, pirfenidone, and the matrix metalloproteinase inhibitor, batimastat,
      during acute lung injury in mice.
AB  - Matrix metalloproteinases (MMPs) are potent to degrade basement membrane collagen
      associated with acute lung injury in inflammatory processes. We have investigated
      effects of pirfenidone, antifibrotic agent, and batimastat, inhibitor of MMPs, on
      gelatinase activities, on release of tumor necrosis factor-alpha (TNF-alpha) and
      transforming growth factor-beta (TGF-beta), as well as on recruitment of
      inflammatory cells in bronchoalveolar lavage (BAL) fluid after aerosol
      administration of lipopolysaccharide (LPS) in mice. Pretreatment with pirfenidone
      reduced neutrophil recruitment, TNF-alpha and TGF-beta levels, and MMP-9
      secretion. In contrast, pretreatment with batimastat (30 or 60 mg/kg, i.p.) only
      reduced TNF-alpha and TGF-beta levels. Batimastat did not reduce MMP secretion in
      BAL fluid but inhibited MMP-9 activity. The increase in tissue inhibitor of
      matrix metalloproteinase (TIMP)-1 induced by LPS was not modified by the two
      drugs. These findings demonstrate that the two drugs can inhibit the in vivo
      increase in MMP induced by LPS, batimastat with a direct inhibitor effect on MMP
      activity and pirfenidone as a consequence of its antiinflammatory effect.

PMID- 11525780
TI  - Pharmacological modulation of allergic inflammation in the rat airways and
      association with mast cell heterogeneity.
AB  - Administration of ovalbumin by aerosol to sensitised rats produced a rapid (15
      min) protein exudation in different airway tissues, as determined by Evans blue
      staining. This was associated with marked mast cell degranulation determined by
      histological examination, with there being no difference between mucosal and
      connective tissue mast cells. A 5-day administration regimen with compound 48/80
      selectively depleted connective tissue mast cell (positive to berberine staining)
      without modifying ovalbumin-induced plasma protein extravasation. Treatment of
      rats with dexamethasone (1 mg/kg, -12 h) or nor-dihydroguaiaretic acid (30 mg/kg
      i.p., -30 min) significantly reduced ovalbumin-induced protein extravasation and
      preserved mucosal mast cell morphology. Indomethacin (4 mg/kg i.v., -30 min)
      exerted no effect on either parameter. In conclusion, we propose the mucosal mast
      cell as a target cell responsible at least partly for the inhibitory actions of
      known anti-inflammatory drugs. We suggest an involvement of endogenous
      leukotriene(s), but not prostanoid(s), in mucosal mast cell
      activation/degranulation.

PMID- 11525781
TI  - Inhibition of neutrophil elastase activity attenuates complement-mediated lung
      injury in the hamster.
AB  - The role of neutrophil elastase in complement-mediated lung injury was examined
      in hamsters using a specific neutrophil elastase inhibitor, sodium N-[2-[4-(2,2
      dimethylpropionyloxy)phenylsulfonylamino]benzoyl]aminoacetate tetrahydrate
      (sivelestat). Intravenous injection with cobra venom factor (CVF) into hamsters
      transiently increased plasma neutrophil elastase activity by about 10-fold. This
      increase was followed by a sustained increase in lung vascular [125I]bovine serum
      albumin permeability peaking 30 min after CVF injection. The increase in lung
      vascular permeability was associated with neutrophil accumulation in lung tissue
      and an increase in protein concentration in the bronchoalveolar lavage fluid.
      Inhibition of the elevated plasma neutrophil elastase activity (36.5%, 66.9% and
      104.3%) by continuous i.v. infusion with sivelestat (0.1, 0.3 and 1 mg/kg/h),
      dose-dependently attenuated the increase in lung vascular permeability 30 min
      after CVF injection. Furthermore, sivelestat at 1 mg/kg/h almost totally
      prevented the increase in protein concentration in the bronchoalveolar lavage
      fluid without affecting lung neutrophil accumulation. These results suggest that
      neutrophil elastase is an important mediator in complement-mediated acute lung
      injury.

PMID- 11525782
TI  - Modulation of islet ATP content by inhibition or stimulation of the Na(+)/K(+)
      pump.
AB  - High (30 mM) K(+), known to cause beta-cell membrane depolarisation,
      significantly decreased the islet total ATP content, supporting the view that
      beta-cell membrane depolarisation can activate the ATP-consuming Na(+)/K(+) pump.
      Ouabain (1 mM) did not change the islet ATP content after 5-15 min of incubation
      in the absence or presence of 3 mM glucose but reduced it after 30 min, and in
      the presence of 20 mM glucose, the reduction by ouabain occurred already after 15
      min. Incubation of islets with ouabain for 60 min decreased the islet ATP content
      in the presence of 3, 10 or 20 mM glucose or 30 mM K(+). Also, the islet glucose
      oxidation rate was decreased by ouabain. When K(+) deficiency was used to inhibit
      the Na(+)/K(+) pump, no change in ATP content was observed irrespective of
      glucose concentration, although K(+) deficiency caused a slight inhibition of the
      glucose oxidation rate. Diazoxide reduced the islet glucose oxidation rate and
      increased the islet ATP content in the presence of 20 mM glucose. There may exist
      a feedback mechanism decreasing the flow of glucose metabolism in response to
      reduced ATP consumption by the Na(+)/K(+) pump.

PMID- 11525784
TI  - The selective sigma(1) receptor agonist, 1-(3,4-dimethoxyphenethyl)-4
      (phenylpropyl)piperazine (SA4503), blocks the acquisition of the conditioned
      place preference response to (-)-nicotine in rats.
AB  - We examined the effect of the sigma(1) receptor agonist, 1-(3,4
      dimethoxyphenethyl)-4-(phenylpropyl)piperazine (SA4503), on the acquisition of
      the conditioned place preference response to subcutaneously administered (-)
      nicotine in rats. (-)-Nicotine, but not SA4503 or vehicle, produced a significant
      conditioned place preference response. Pretreatment of animals with either 1 or 3
      mg/kg of SA4503 significantly attenuated the conditioned place preference
      response to (-)-nicotine.

PMID- 11525785
TI  - Hypopyon uveitis.
AB  - Hypopyon uveitis has inflammatory, infective, and neoplastic causes and a high
      association with systemic disease. Careful questioning of the patient and
      detailed examination of the eye for other signs is necessary to guide the
      differential diagnosis and relevant investigations. Because the underlying causes
      require very different types of investigation and, if missed, can have serious
      sequelae for the patient, a rational approach based on the understanding of the
      causes of hypopyon uveitis is imperative. In this review, hypopyon uveitis is
      considered in the context of the associated ocular and systemic diseases that
      cause it.

PMID- 11525786
TI  - Ophthalmic manifestations of lightning strike.
AB  - Every year in the USA, 100-150 people die and 1000-1500 others are injured by
      lightning strikes. Ophthalmic and neurologic injuries from lightning strike are
      common. The most common permanent ocular sequela is cataract, but many areas of
      the eye can be affected. Prompt evaluation by an ophthalmologist is imperative
      for maximizing outcomes. Incidence and mechanisms of lightning strike injury are
      summarized, with special emphasis on the treatment of ocular injuries.

PMID- 11525787
TI  - Clostridium botulinum and the ophthalmologist: a review of botulism, including
      biological warfare ramifications of botulinum toxin.
AB  - The anaerobic bacterium Clostridium botulinum causes disease by elaborating an
      extremely potent neurotoxin that inhibits release of acetylcholine at presynaptic
      nerve endings, thereby resulting in a descending flaccid paralysis and autonomic
      nervous system dysfunction. Possible ophthalmological effects of this neurotoxin
      are many and typically constitute the earliest manifestations of botulism. This
      review summarizes the medical literature on botulism with regard to historical
      perspective, epidemiology, clinical manifestations, and treatment.
      Ophthalmological findings of botulism are tabulated and their frequencies are
      provided. Finally, the bioterrorism/biologic warfare ramifications of botulinum
      toxin are briefly discussed.

PMID- 11525788
TI  - Visual loss in childhood.
AB  - An eight-year-old girl presented with vision loss and optic atrophy. Neuro
      imaging revealed a sellar mass, which when biopsied proved to be a
      chiasmatic/hypothalamic glioma. The differential diagnosis of a sellar mass in
      childhood is discussed, and the presentation and management of
      chiasmatic/hypothalamic gliomas is reviewed.

PMID- 11525790
TI  - Complementary and alternative medicine for glaucoma.
AB  - Given the recent interest in complementary and alternative medicine (CAM), some
      patients may seek such treatments to supplement their traditional glaucoma
      management. The prevalence of CAM use for glaucoma is approximately 5%. We
      reviewed the literature to determine the potential benefit of various alternative
      treatments. Aside from a temporary osmotic effect from high dose intravenous
      ascorbic acid, there is no evidence that megavitamin supplementation has a
      beneficial effect on glaucoma. During exercise, autoregulation in healthy eyes
      seems to maintain a consistent blood flow rate to the optic nerve despite
      fluctuations in intraocular pressure (IOP). In a glaucomatous eye, the very
      modest IOP-lowering that follows exercise may be offset by the initial elevation
      in IOP that occurs when one first initiates exercise. At this time, there is no
      evidence to encourage or discourage the use of special diets, acupuncture,
      relaxation techniques, or therapeutic touch specifically for the treatment of
      glaucoma. Very little research has been done on the majority of herbal remedies
      with regard to their treatment of glaucoma. Marijuana can cause a profound
      lowering of IOP, but the high nonresponse rate, short half life, and significant
      toxicity are strong indicators that it is not an appropriate therapeutic agent.
      Ginkgo biloba and some other Chinese herbal remedies do not affect IOP, but may
      improve blood flow to the optic nerve and, as such, may have a beneficial effect
      on glaucoma. These agents have recognized toxicities. Although there are some
      well-designed studies of alternative treatments, many of the recommendations for
      using alternative treatments are currently unsupported by the data provided.

PMID- 11525791
TI  - Disk edema and cranial MRI optic nerve enhancement: how long is too long?
AB  - A 43-year-old woman presented with painful visual loss and optic disk edema in
      the right eye (OD) diagnosed as optic neuritis. Initial non-gadolinium-enhanced
      fat suppressed cranial magnetic resonance imaging (MRI) was normal. Three months
      later, the disk edema persisted and a gadolinium-enhanced MRI scan of the brain
      and orbits with fat suppression showed enhancement of the optic nerve OD, most
      consistent with an optic nerve sheath meningioma. The diagnostic difference
      between optic neuritis and optic nerve sheath meningioma is discussed.

PMID- 11525792
TI  - Retinal microvascular abnormalities and their relationship with hypertension,
      cardiovascular disease, and mortality.
AB  - Retinal microvascular abnormalities, such as generalized and focal arteriolar
      narrowing, arteriovenous nicking and retinopathy, reflect cumulative vascular
      damage from hypertension, aging, and other processes. Epidemiological studies
      indicate that these abnormalities can be observed in 2-15% of the nondiabetic
      general population and are strongly and consistently associated with elevated
      blood pressure. Generalized arteriolar narrowing and arteriovenous nicking also
      appear to be irreversible long-term markers of hypertension, related not only to
      current but past blood pressure levels as well. There are data supporting an
      association between retinal microvascular abnormalities and stroke, but there is
      no convincing evidence of an independent or direct association with
      atherosclerosis, ischemic heart disease, or cardiovascular mortality. New
      computer-related imaging methods are currently being developed to detect the
      presence and severity of retinal arteriolar narrowing and other microvascular
      characteristics. When reliably quantified, retinal microvascular abnormalities
      may be useful as risk indicators for cerebrovascular diseases.

PMID- 11525793
TI  - Dr. William Briggs: ophthalmic physician at St. Thomas' Hospital, London.
AB  - William Briggs, MD, established himself as one of the first ophthalmic
      physicians, whom today we would call a neuro-ophthalmologist, to practice in the
      United Kingdom. After graduating with an MD from Cambridge in 1677, and while a
      Fellow of Corpus Christi College, he carried out original studies in visual
      anatomy and physiology. He described and named the optic papilla and the retinal
      nerve fibers in his book Ophthalmographia, published in 1676. He published his
      New Theory of Vision in 1682. While at Cambridge, he was a contemporary and a
      friend of Isaac Newton, with whom Briggs worked but who, in matters of visual
      anatomy and physiology, came to reach different conclusions from Briggs. In 1683,
      Briggs came to London to practice as a physician at St. Thomas' Hospital, where
      he established a considerable reputation as an ophthalmologist. For political
      reasons he was forced to resign from the Hospital prematurely.

PMID- 11525794
TI  - Increased post-traumatic survival of neurons in IL-6-knockout mice on a
      background of EAE susceptibility.
AB  - Axonal injury initiates a process of neuronal degeneration, with resulting death
      of neuronal cell bodies. We show here that in C57BL/6J mice, previously shown to
      have a limited ability to manifest a post-traumatic protective immunity, the rate
      of neuronal survival is increased if IL-6 is deficient during the first 24 hours
      after optic nerve injury. Immunocytochemical staining preformed 7 days after the
      injury revealed an increased number of activated microglia in the IL-6-deficient
      mice compared to the wild-type mice. In addition, IL-6-deficient mice showed an
      increased resistance to glutamate toxicity. These findings suggest that the
      presence of IL-6 during the early post-traumatic phase, at least in mice that are
      susceptible to autoimmune disease development, has a negative effect on neuronal
      survival. This further substantiates the contention that whether immune-derived
      factors are beneficial or harmful for nerve recovery after injury depends on the
      phenotype of the immune cells and the timing and nature of their dialog with the
      damaged neural tissue.

PMID- 11525795
TI  - Suppression of the transcriptional activity and DNA binding of nuclear factor
      kappa B by a paraneoplastic cerebellar degeneration-associated antigen.
AB  - Paraneoplastic cerebellar degeneration (PCD) associated with gynecological
      malignancies is a disorder in which an autoimmune mechanism has been suggested,
      and both antibody- and cell-mediated immune responses exist against pcd17/cdr2, a
      neural protein expressed in cerebellar Purkinje neurons and brainstem neurons. In
      this report, we describe that pcd17 can suppress the basal or activated NF-kappaB
      dependent transcriptional activity in a co-transfection study. The DNA binding of
      constitutive NF-kappaB complexes decreased in the nucleus of TNF-alpha-stimulated
      neuroblastoma cells, though pcd17 does not bind to classical NF-kappaB consensus
      site. These data indicate that pcd17 is a potential repressor for NF-kappaB
      dependent gene transcription in neurons.

PMID- 11525796
TI  - Rag-1-dependent cells are necessary for 1,25-dihydroxyvitamin D(3) prevention of
      experimental autoimmune encephalomyelitis.
AB  - Multiple sclerosis (MS) is a demyelinating disease involving genetic and
      environmental risk factors. Geographic, genetic, and biological evidence suggests
      that one environmental risk factor may be lack of vitamin D. Here, we
      investigated how 1,25-dihydroxyvitamin D(3) (1,25-(OH)(2)D(3)) inhibits
      experimental autoimmune encephalomyelitis (EAE), an MS model. The experiments
      used adoptive transfer of TCR-transgenic (TCR1) cells specific for myelin basic
      protein (MBP) peptide into unprimed recipients. When unprimed TCR1 splenocytes
      were transferred, and the recipients were immunized with peptide, the mock
      treated mice developed EAE, but the 1,25-(OH)(2)D(3)-treated recipients remained
      disease-free. Both groups had TCR1 T cells that proliferated in response to MBP
      Ac1-11 and produced IFN-gamma but not IL-4 in the lymph node. In the central
      nervous system (CNS), the mock-treated mice had activated TCR1 T cells that
      produced IFN-gamma but not IL-4, while the 1,25-(OH)(2)D(3)-treated mice had TCR1
      T cells with a non-activated phenotype that did not produce IFN-gamma or IL-4.
      When activated TCR1 T cells producing IFN-gamma were transferred into unprimed
      mice, the mock-treated and the 1,25-(OH)(2)D(3)-treated recipients developed EAE.
      Likewise, the 1,25-(OH)(2)D(3) did not inhibit Th1 cell IFN-gamma production or
      promote Th2 cell genesis or IL-4 production in vitro. Finally, the 1,25
      (OH)(2)D(3) inhibited EAE in MBP-specific TCR-transgenic mice that were Rag-1(+),
      but not in animals that were Rag-1-null. Together, these data refute the
      hypothesis that the hormone inhibits Th1 cell genesis or function directly or
      through an action on antigen-presenting cells, or promotes Th2 cell genesis or
      function. Instead, the evidence supports a model wherein the 1,25-(OH)(2)D(3)
      acts through a Rag-1-dependent cell to limit the occurrence of activated,
      autoreactive T cells in the CNS.

PMID- 11525797
TI  - Time course of IgM antibodies which block anti-myelin basic protein IgG
      antibodies associated with development of experimental autoimmune
      encephalomyelitis in rabbits.
AB  - Several authors have demonstrated the presence in normal sera of antibodies that
      inhibit binding of a variety of autoantibodies. These inhibitory or blocking
      antibodies are generally considered to play a role in humoral self-tolerance. We
      examined sera from normal rabbits and from rabbits with experimental autoimmune
      encephalomyelitis (EAE), in search for antibodies capable to inhibit reactivity
      of autoantibodies directed to myelin basic protein (MBP). Rabbits injected with
      bovine myelin in complete Freund's adjuvant (EAE rabbits) or with adjuvant alone
      (control rabbits) were bled at various intervals post-injection. Sera were
      subjected to chomatography on a protein A-Sepharose column, retained and
      nonretained fractions were collected, and ability of these fractions to block
      reactivity of affinity-purified anti-MBP IgG-antibodies was analyzed by
      immunoblot technique. Protein A nonretained fraction from control rabbits
      inhibited anti-MBP IgG reactivity to the same degree at all intervals tested,
      whereas the same fraction from EAE animals showed an increase in inhibitory
      activity after induction of the disease. This inhibitory activity declined with
      the onset of clinical symptoms, and remained low in rabbits that did not recover
      from the disease. In contrast, the inhibitory activity remained at maximum value
      in EAE rabbits with spontaneous remission of clinical symptoms. We showed that
      the inhibitory activity is due to IgM-antibodies, and discussed the role of these
      antibodies in the development of EAE.

PMID- 11525798
TI  - Effects of interleukin-2 on the expression of corticotropin-releasing hormone in
      nerves and lymphoid cells in secondary lymphoid organs from the Fischer 344 rat.
AB  - This study examined the influence of interleukin (IL)-2 on corticotropin
      releasing hormone (CRH) immunoreactivity in the Fischer 344 (F344) rat spleen.
      Rats were given either vehicle or 1, 10, 25, 50, 100, or 200 ng of human
      recombinant (hr)IL-2 by intraperitoneal (i.p.) injection, and were sacrificed
      0.5, 1, 4, 12, or 24 h after treatment. Spleens and mesenteric lymph nodes were
      prepared for immunocytochemistry to localize CRH. In spleens from vehicle-treated
      animals, CRH immunoreactivity was present in several types of cells of the immune
      system, but CRH(+) nerves were not observed in either spleens or lymph nodes from
      vehicle-treated animals. Treatment with IL-2 induced CRH expression in nerves in
      the spleen in a dose- and time-dependent manner. CRH(+) nerves were not found in
      the mesenteric lymph nodes after IL-2 treatment, instead a dramatic time- and
      dose-dependent accumulation of CRH(+) cells (resembling small lymphocytes and
      large granular mononuclear cells) in the cortex and medulla. These findings
      indicate that IL-2 stimulates the synthesis of CRH in nerves that innervate the
      F344 rat spleen, and promote the appearance of CRH(+) immunocytes into draining
      mesenteric lymph nodes.

PMID- 11525799
TI  - Endomorphins 1 and 2 modulate chemotaxis, phagocytosis and superoxide anion
      production by microglia.
AB  - We evaluate the role of endomorphins 1 and 2 on microglial functions.
      Endomorphins 1 and 2 blocked phagocytosis of Escherichia coli. In addition, both
      markedly inhibited chemotaxis toward zymosan-activated serum. In contrast, when
      microglia was preincubated with these endomorphins, followed by incubation with
      LPS before stimulation with phorbol 12-myristate 13-acetate (PMA) at 200 nM, they
      potentiated superoxide anion production. Furthermore, when microglia was
      preincubated with these endomorphins together with PMA at 20 nM, followed by
      stimulation with PMA at 200 nM, superoxide anion production was potentiated.
      These results suggest that endomorphins 1 and 2 modulate phagocytosis, chemotaxis
      and superoxide anion production by microglia.

PMID- 11525800
TI  - Intracerebroventricular interleukin-1beta impairs clearance of tumor cells from
      the lungs: role of brain prostaglandins.
AB  - We have previously demonstrated that central administration of interleukin (IL)
      1beta suppresses natural killer (NK) cell activity, impairs NK-mediated lung
      clearance of tumor cells, and enhances tumor colonization. The central pathways
      activated by IL-1beta are as yet unknown. Using an in vivo model of tumor
      colonization, this study examined the role of central noradrenergic, opioid and
      prostaglandin mechanisms in mediating the effect of IL-1beta on lung clearance of
      tumor cells. We demonstrate that central noradrenergic and opioid systems are not
      critically involved in this effect. Neither depletion of central noradrenergic
      pathways, or administration of the opioid antagonist, naltrexone (50 ug), blocked
      the impaired lung clearance of MADB106 tumor cells induced by central
      administration of IL-1beta (20 ng). Central prostaglandins (PGs) do, however,
      appear to play a critical role. Central administration of the prostaglandin
      antagonist, diclofenac (250 ug), but not ibuprofen, completely blocked the effect
      of IL-1beta on lung clearance of tumor cells. Antagonism of the effects of IL
      1beta was shown to be due to the effects of centrally and not of peripherally
      acting prostaglandins.

PMID- 11525801
TI  - Expression of Golli mRNA during development in primary immune lymphoid organs of
      the rat.
AB  - The gene-of-the-oligodendrocyte lineage (Golli)-MBP transcription unit contains
      three Golli-specific exons together with eight exons of the "classical" myelin
      basic protein (MBP) gene, yielding alternatively spliced proteins which share
      amino acid sequence with MBP. Unlike MBP, a late antigen expressed only in the
      nervous system, Golli gene products are expressed pre- and post-natally at many
      sites. In this study, we determined the sequence of Golli in rat by RT-PCR and 5'
      RACE and showed that Golli sequences are expressed in primary lymphoid organs as
      early as e16.5, which could explain the anergic rat T cell response we previously
      observed in Golli-induced meningitis.

PMID- 11525802
TI  - Th2 cells support intrinsic anti-inflammatory properties of the brain.
AB  - In experimental autoimmune encephalomyelitis (EAE), Th1 cells are responsible for
      disease induction while Th2 cells can be protective. To address the mechanisms of
      this differential behavior, we utilized organotypic murine entorhinal-hippocampal
      slice cultures to analyze interactions between myelin basic protein-specific Th1
      and Th2 cells with microglial cells. While both Th1 and Th2 cells induced CD40
      expression, only Th1 cells induced intercellular adhesion molecule-1 (ICAM-1)
      expression on microglia. Moreover, Th2 cells prevented or even reversed Th1
      induced ICAM-1 upregulation. Evidently, Th2 cells could diminish Th1-induced
      inflammatory reactions and actively support the resting state of microglia, which
      could be one mechanism of Th2-mediated remission of neuroinflammation during EAE.

PMID- 11525803
TI  - DA rat NK(+)CD3(-) cells inhibit autoreactive T-cell responses.
AB  - We isolated natural killer (NK) cells from DA rat bone marrow (BM) by staining
      with PE anti-NKR-P1A and FACS sorting (>98% NK(+)). The purified NK cells inhibit
      T-cell proliferation in a dosage-dependent fashion and suppressed production of
      the proinflammatory Th1 cytokine, IFN-gamma. When activated in vitro with Con A
      supernatant (CAS), the purified NK cells secrete the beta-chemokine monocyte
      chemoattractant protein-1 (MCP-1) and upregulate MCP-1 mRNA. The activated NK
      cells also express IFN-gamma mRNA. Sorted NK(+)CD3(-) cells, from which NKT cells
      have been excluded, also inhibit autoreactive T-cell responses to myelin basic
      protein (MBP). These findings are consistent with a role for conventional NK
      cells in maintaining immune homeostasis, by eliminating autoreactive T cells that
      have inadvertently become activated.

PMID- 11525804
TI  - Serum autoantibody responses to myelin oligodendrocyte glycoprotein and myelin
      basic protein in X-linked adrenoleukodystrophy and multiple sclerosis.
AB  - We analyzed the sera of 51 patients with various phenotypes of X-linked
      adrenoleukodystrophy (X-ALD), 20 patients with multiple sclerosis (MS) and 22
      healthy volunteers for the presence of autoantibodies specific for the
      recombinant extracellular immunoglobulin-like domain of human myelin
      oligodendrocyte glycoprotein (rhMOG(Igd)) and myelin basic protein (MBP). Anti
      rhMOG(Igd) autoantibodies were significantly more frequent in X-ALD and MS
      patients as opposed to healthy individuals (p<0.05). Anti-MBP autoantibodies were
      present in about one-fourth of X-ALD and MS patients but in less than 10% of
      healthy individuals. Anti-rhMOG(Igd) autoantibody responses were not accompanied
      by increased T cell reactivity against rhMOG(Igd). These findings may have
      important implications for the understanding of humoral anti-myelin
      immunoreactivity in demyelinating diseases of the central nervous system such as
      X-ALD and MS.

PMID- 11525805
TI  - No linkage or association of the nitric oxide synthase genes to multiple
      sclerosis.
AB  - Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous
      system (CNS) of unknown etiology. Nitric oxide (NO) is a free radical that
      participates in a variety of biological processes. It is an important mediator in
      the immune response. Several studies indicate involvement of NO in the
      pathogenesis of MS. We studied five markers within the three NO synthase genes
      with regards to susceptibility and disease course in 156 affected sib-pairs and
      in 96 "benign" and 96 "severe" definite MS patients and 148 controls. We found no
      significant association or evidence for linkage in our data sets.

PMID- 11525806
TI  - Allelic expression and interleukin-2 polymorphisms in multiple sclerosis.
AB  - We have investigated the association of two single nucleotide polymorphisms
      (SNPs) at positions -384 and 114 in the human interleukin-2 (hIL-2) with multiple
      sclerosis (MS). For two of the -384 genotypes (G/T, T/T), we observed an
      association with the susceptibility to secondary progressive (SP) course of MS
      (P=0.005 and P=0.013, respectively). Expression level differences of the IL-2
      alleles (between one- and three-fold) were not attributable to the -384 promoter
      polymorphism. These data indicate for the first time the relevance of the il-2
      gene locus in human MS and its possible involvement in other autoimmune diseases.

PMID- 11525807
TI  - Striatal antibodies in children with Tourette's syndrome: multivariate
      discriminant analysis of IgG repertoires.
AB  - Antineuronal antibodies have been postulated to be the underlying pathophysiology
      in TS and other neuropsychiatric disorders. Serum antibodies from 20 children
      with TS, and 21 control subjects against human striatum, globus pallidus, muscle,
      and HTB-10 cells were assayed by Western blot techniques. A MANOVA differentiated
      between TS and control blots, and a discriminant analysis demonstrated which
      variables contributed most to differences between groups. Prominent differences
      between TS and control blots were identified using striatal epitopes in contrast
      to similar patterns shown between groups for globus pallidus, muscle and HTB-10
      tissue, supporting striatal autoimmune involvement in TS pathophysiology.

PMID- 11525808
TI  - IgM monoclonal antibody against terminal moiety of GM2, GalNAc-GD1a and GalNAc
      GM1b from a pure motor chronic demyelinating polyneuropathy patient: effects on
      neurotransmitter release.
AB  - We describe a patient with a pure motor chronic demyelinating polyneuropathy with
      an IgM monoclonal component showing anti-GM2, GalNAc-GD1a and GalNAc-GM1b
      reactivity whose common epitope appears to be -[GalNAcbeta1-4Gal(3
      2alphaNeuAc)beta1]. We used intracellular recording to study how IgM from this
      patient affected neurotransmitter release in the mouse diaphragm in vitro. Adding
      serum (and specifically, the purified monoclonal IgM component) blocked the nerve
      evoked response in both quantal content and evoked endplate potential (EPP)
      amplitude in a complement-independent and reversible manner. The IgM increased
      the frequency of spontaneous miniature endplate potentials (MEPPs) in a
      complement-dependent and reversible manner but had no effect on MEPP amplitude.

PMID- 11525809
TI  - Novel monoclonal antibodies against proteolipid protein peptide 139-151
      demonstrate demyelination and myelin uptake by macrophages in MS and marmoset EAE
      lesions.
AB  - Experimental autoimmune encephalomyelitis (EAE) induced by immunization of mice
      with epitopes of the proteolipid protein (PLP), a major myelin constituent, forms
      a useful model for the study of multiple sclerosis (MS). In addition, MS patients
      display PLP-specific T- and B-cell responses, suggesting that PLP reactivity is
      relevant to pathogenesis.Here, the generation and characterization of a panel of
      mouse monoclonal antibodies (Mab) against PLP139-151, the prominent
      encephalitogenic sequence in SJL/J mice is described. Five Mab were generated by
      conventional immunization of an SJL/J mouse and hybridoma generation. These Mab
      reacted well with the PLP139-151 peptide in ELISA and belonged to the IgG2a and
      IgG2b subclasses, consistent with CD4+ T helper 1-cell-supported antibody
      formation. The Mab also efficiently detected PLP peptide-BSA conjugates in
      Western blot, confirming their multi-assay applicability. The Mab were
      subsequently used to determine the occurrence of demyelination in brains of MS
      patients and marmoset monkeys with EAE. Immunohistochemistry on both paraffin and
      frozen sections demonstrated a homogeneous expression of PLP139-151 in normal
      myelin, and a complete absence in lesions containing demyelinated areas,
      confirming that the Mab can be used as a general myelin marker. In active
      demyelinating MS lesions, the Mab visualized the peptide in the cytoplasm of
      macrophages containing phagocytosed myelin. In conclusion, this panel of Mab
      against the encephalitogenic PLP139-151 epitope forms a useful tool for further
      study of autoantigen expression, demyelination/remyelination and the staging of
      lesional activity in MS patients, as well as in EAE models in distinct animal
      species.

PMID- 11525810
TI  - Variable patterns of anti-GM(1) IgM-antibody populations defined by affinity and
      fine specificity in patients with motor syndromes: evidence for their random
      origin.
AB  - Elevated titers of serum antibodies against GM(1)-ganglioside are associated with
      a variety of autoimmune neuropathies. Although much evidence indicates that these
      autoantibodies play a primary role in the disease processes, the mechanism of
      their appearance is unclear. Low-affinity anti-GM(1) antibodies of the IgM
      isotype are part of the normal human immunological repertoire. In patients with
      motor syndromes, we found that in addition to the usual anti-GM(1) antibodies,
      the sera contain IgM-antibodies that recognize GM(1) with higher affinity and/or
      different specificity. This latter type of antibodies was not detected in other
      autoimmune diseases. We studied the fine specificity of both normal and motor
      disease-associated antibodies using HPTLC-immunostaining of GM(1) and
      structurally related glycolipids, soluble antigen binding inhibition, and GM(1)
      affinity columns. Normal low-affinity anti-GM(1) antibodies cross-react with
      GA(1) and/or GD(1b). In the motor syndrome patients, different populations of
      antibodies characterized by their affinity and cross-reactivity were detected.
      Although one population is relatively common (low affinity, not cross-reacting
      with GA(1) and GD(1b)), there are remarkably few sera having the same set of
      populations. These results suggest that the appearance of the new antibody
      populations is a random process. When the different antibody populations were
      analyzed in relation to the three-dimensional structure of GM(1), a restricted
      area of the GM(1) oligosaccharide (the terminal Galbeta1-3GalNAc) was found to be
      involved in binding of normal anti-GM(1) antibodies. Patient antibodies recognize
      slightly different areas, including additional regions of the GM(1) molecule such
      as the NeuNAc residue. We hypothesize that disease-associated antibodies may
      originate by spontaneous mutation of normal occurring antibodies.

PMID- 11525811
TI  - Glatiramer acetate (GA) induces IL-13/IL-5 secretion in naive T cells.
AB  - In order to define possible mechanisms of immunomodulation by glatiramer acetate
      (GA), we investigated the primary in vitro cytokine response of peripheral blood
      mononuclear cells (PBMCs) and T-cell subpopulations. In PBMCs from healthy
      subjects and untreated patients with multiple sclerosis (MS) GA-induced T-cell
      proliferation and mRNA expression/cytokine, secretion of IL-13 and IL-5 but not
      of IL-10, TGF-beta or IL-12, IL-4 was detected at the mRNA level only. IFN-gamma
      was induced in a few subjects at very low concentrations. The response to GA was
      driven by the CD4(+)/CD45RA(+) T-cell subpopulation and was mediated by T-cell
      receptor (TCR) engagement as determined by anti-TCR blocking antibodies. The
      findings are compatible with the hypothesis that GA functions as partial or weak
      TCR-agonist activating naive T cells to produce the Th2 cytokines IL-13 and IL-5.

PMID- 11525812
TI  - Increased percentage of IL-12+ monocytes in the blood correlates with the
      presence of active MRI lesions in MS.
AB  - Interleukin (IL)-12 is a cytokine thought to play a major role in the
      pathogenesis of multiple sclerosis (MS). We have previously shown that patients
      with progressive MS have a high percentage of IL-12-producing monocytes in the
      blood compared to normal individuals. We analyzed 269 blood samples from 189 MS
      patients for the percentage of IL-12-producing monocytes. We found that the
      increased IL-12 expression correlates with disability, as measured by the
      Expanded Disability Status Scale (EDSS), and with disease activity, measured by
      the presence of gadolinium-enhancing magnetic resonance imaging (MRI) lesions.

PMID- 11525814
TI  - Single nucleotide polymorphisms and recombination rate in humans.
AB  - Levels of heterozygosity for single nucleotide polymorphisms vary by more than
      one order of magnitude in different regions of the human genome. Regional
      differences in the rate of recombination explain a substantial fraction of the
      variation in levels of nucleotide polymorphism, consistent with the widespread
      action of natural selection at the molecular level.

PMID- 11525815
TI  - Modularity in the gain and loss of genes: applications for function prediction.
AB  - Genes that are clustered on multiple genomes and are likely to functionally
      interact tend to be gained or lost together during genome evolution. Here, we
      demonstrate that exceptions to this pattern indicate relatively distant
      functional interactions between the encoded proteins. Hence, this can be used to
      divide predicted clusters of functionally interacting proteins into sub-clusters,
      and as such, to refine the prediction of their function and functional
      interactions.

PMID- 11525816
TI  - 2R or not 2R?

PMID- 11525833
TI  - On the allelic spectrum of human disease.
AB  - Human disease genes show enormous variation in their allelic spectra; that is, in
      the number and population frequency of the disease-predisposing alleles at the
      loci. For some genes, there are a few predominant disease alleles. For others,
      there is a wide range of disease alleles, each relatively rare. The allelic
      spectrum is important: disease genes with only a few deleterious alleles can be
      more readily identified and are more amenable to clinical testing. Here, we weave
      together strands from the human mutation and population genetics literature to
      provide a framework for understanding and predicting the allelic spectra of
      disease genes. The theory does a reasonable job for diseases where the genetic
      etiology is well understood. It also has bearing on the Common Disease/Common
      Variants (CD/CV) hypothesis, predicting that at loci where the total frequency of
      disease alleles is not too small, disease loci will have relatively simple
      spectra.

PMID- 11525834
TI  - PDZ proteins and polarity: functions from the fly.
AB  - Proteins that contain PDZ domains have been implicated in the localization of
      interacting partners to specific regions of the cell membrane. Although PDZ
      proteins that bind to a number of important mammalian proteins have been
      isolated, the significance of these interactions is unclear. In recent years, the
      fruit fly has emerged as a rich system for genetic analysis of PDZ protein
      function. Here, I discuss what the Drosophila data tell us about the roles and
      mechanisms of PDZ protein activity, and how this informs our understanding of PDZ
      function in other organisms.

PMID- 11525835
TI  - CTCF is a uniquely versatile transcription regulator linked to epigenetics and
      disease.
AB  - CTCF is an evolutionarily conserved zinc finger (ZF) phosphoprotein that binds
      through combinatorial use of its 11 ZFs to approximately 50 bp target sites that
      have remarkable sequence variation. Formation of different CTCF-DNA complexes,
      some of which are methylation-sensitive, results in distinct functions, including
      gene activation, repression, silencing and chromatin insulation. Disrupting the
      spectrum of target specificities by ZF mutations or by abnormal selective
      methylation of targets is associated with cancer. CTCF emerges, therefore, as a
      central player in networks linking expression domains with epigenetics and cell
      growth regulation.

PMID- 11525836
TI  - Unfolding the role of chaperones and chaperonins in human disease.
AB  - Molecular chaperones comprise several highly conserved families of related
      proteins, many of which are also heat shock proteins. Chaperone proteins are
      crucial for the maintenance of native protein conformation and recent research
      has demonstrated several mechanisms where defective chaperone proteins have
      pathogenic consequences. In this article, we describe the structure and function
      of chaperones in bacterial and eukaryotic cells, focusing on the chaperonin class
      of chaperones. We then summarize contemporary research concerning the role of
      these proteins in several human diseases, concentrating on the genes coding for
      chaperone and chaperonin proteins and the importance of chaperones in
      neurodegenerative diseases and as modifiers of amino acid substitution mutations
      in other proteins.

PMID- 11525837
TI  - Oranges and lemons: clues to the taxonomy of Citrus from molecular markers.
AB  - Go into any grocery store and one is confronted with an array of Citrus fruit:
      oranges, grapefruit, mandarins (tangerines), lemons and limes. This is rich
      bounty for the shopper, but taxonomists are perplexed as to how to classify the
      various kinds of Citrus that have existed since antiquity. Now, thanks to new
      genetic and molecular biological techniques, the relationships between these
      fruit are being unraveled and show that there are probably only three true
      species.

PMID- 11525839
TI  - Recent developments in the field of antitumour anthracyclines.

PMID- 11525840
TI  - 3,8-diazabicyclo--[3.2.1]-octane derivatives as analogues of ambasilide, a Class
      III antiarrhythmic agent.
AB  - Ambasilide, a representative of Class III antiarrhythmics, was reported to
      prolong the cardiac action potential duration in the dog, with little or no
      effect on Ca and Na currents. We synthesised a series of ambasilide analogues,
      having the 3,8-diazabicyclo-[3.2.1]-octane moiety instead of the 3,7-diazabicyclo
      [3.3.1]-nonane present in ambasilide. The compounds were tested both in vitro
      extracellular electrophysiological assays and by the conventional microelectrode
      technique. Most of them lengthened the effective refractory period (ERP) with no
      change or slight increase on the impulse conduction time (ICT). Similarly some of
      the tested compounds lengthened the action potential duration (APD), a typical
      Class III feature, without exerting any significant effect on the maximal rate of
      depolarization, therefore apparently lacking Class I antiarrhythmic activity.

PMID- 11525841
TI  - Synthesis and antitumour activity of trimethylsilylpropyl substituted
      benzimidazoles.
AB  - The quaternisation of N-substituted benzimidazoles by heating with various alkyl,
      allyl, propargyl and benzyl chlorides and bromides leads to the formation of
      benzimidazolinium salts. The interaction of N-monosubstituted benzimidazoles with
      various salts (CuCl2, ZnCl2, CoCl2, PdCl2 and AgNO3) yielded stable solid
      complexes. Potential cytotoxic activity of synthesised benzimidazolinium salts
      and benzimidazole metal complexes was tested in vitro on four monolayer tumour
      cell lines: MG-22A (mouse hepatoma), HT-1080 (human fibrosarcoma), B16 (mouse
      melanoma), Neuro 2A (mouse neuroblastoma) and normal mouse fibroblast cells. A
      preliminary analysis of the structure-activity relationship for the benzimidazole
      derivatives clearly indicates that the character of substituents in the
      benzimidazole ring has strong influence on the cytotoxic activity. The insertion
      of the silicon atom into the N-alkyl chain increases the cytotoxic activity of
      benzimidazolinium salts significantly, which show a very significant potency in
      vitro against all studied tumour cell lines, being particularly active in
      experiments with B16 (mouse melanoma). TD50 for the most active compounds are in
      the range 0.001-0.008 microg x ml(-1). Cytotoxicity of benzimidazole metal
      complexes (L2MX2) strongly depends on the metal nature. 1-(3
      trimethylsilylpropyl)benzimidazole in dose 1 mg x kg(-1) inhibits carcinoma S-180
      tumour growth by 62% (on ICR mice).

PMID- 11525842
TI  - Synthesis of substituted benzamides as anti-inflammatory agents that inhibit
      preferentially cyclooxygenase 1 but do not cause gastric damage.
AB  - Parsalmide (5-amino-N-butyl-2-(2-propynyloxy) benzamide) (5a), is a non-steroidal
      anti-inflammatory drug (NSAID), commercialised in Italy until 1985 with the brand
      name of Synovial(R), that has been widely used to treat arthritic patient. In
      addition, it was shown to spare gastric mucosa. Here we have synthesised a series
      of novel substituted benzamides, related to Parsalmide, and have evaluated their
      activity in vitro on COX-1 and COX-2 as well as in vivo in the carrageenin
      induced rat paw edema, a classical in vivo anti-inflammatory assay. Compounds 5b,
      11a and 11b, which showed a favourable profile in vitro and in vivo, were
      screened in comparison with Parsalmide for gastrointestinal (GI) tolerability in
      vivo in the rat. Results obtained showed that Parsalmide and compound 11b
      inhibited both COX-1 and COX-2 in vitro as well as they were active in vivo. Both
      compounds were devoid of gastric effect at the efficacious dose. In addition,
      both prevented indomethacin-induced gastric damage. Thus, these compounds may
      guide the definition of a new leading structure with anti-inflammatory activity
      that may allow designing new safer NSAIDs.

PMID- 11525843
TI  - Trypanocidal activity of dicationic compounds related to pentamidine.
AB  - Eight dicationic compounds related to pentamidine were studied for trypanocidal
      activity in seven trypanosome isolates. In vitro studies revealed that diamidines
      are more potent than diimidazolines. For example, 2 (a diamidine) and 4 (a
      diimidazoline) inhibited the growth of KETRI 243 with IC50 values of 2.3 and 900
      nM, respectively. Introduction of polar groups into the linker decreased the
      effectiveness of the compounds against drug-resistant trypanosomes. In compounds
      with a 2-butene linker between the cationic groups, trans-isomers were more
      potent than cis-isomers. The cis- and trans-buteneamidines cured infection caused
      by Trypanosoma brucei brucei (EATRO Lab 110) and protected mice against infection
      by Trypanosoma brucei rhodesiense isolates, some of which are resistant to
      diamidines and melarsoprol.

PMID- 11525844
TI  - Synthesis and antidepressant activities of some 3,5-diphenyl-2-pyrazolines.
AB  - Ten new 3,5-diphenyl-2-pyrazoline derivatives were synthesised by reacting 1,3
      diphenyl-2-propen-1-one with hydrazine hydrate. The chemical structures of the
      compounds were proved by means of their IR, 1H-NMR spectroscopic data and
      microanalyses. The antidepressant activities of these compounds were evaluated by
      the 'Porsolt Behavioural Despair Test' on Swiss-Webster mice. 3-(4-Methoxyphenyl)
      5-(3,4-dimethoxyphenyl)-2-pyrazoline, 3-(4-methoxyphenyl)-5-(2-chloro-3,4
      dimethoxyphenyl)-2-pyrazoline and 3-(4-chlorophenyl)-5-(2-chloro-3,4
      dimethoxyphenyl)-2-pyrazoline reduced 41.94-48.62% immobility times at 100 mgkg(
      1) dose level. In addition, it was found that 4-methoxy and 4-chloro substituents
      on the phenyl ring at position 3 of the pyrazoline ring increased the
      antidepressant activity; the replacement of these groups by bromo and methyl
      substituents decreased activity in mice.

PMID- 11525845
TI  - N-pyridinyl-indole-3-(alkyl)carboxamides and derivatives as potential systemic
      and topical inflammation inhibitors.
AB  - N-substituted-(indol-3-yl)carboxamides 10-15 and alkanamides 16-18 were prepared
      starting from the corresponding acids and submitted to screening for evaluation
      of their anti-inflammatory activity. None of the considered carboxamides
      exhibited significant inhibitory effect in the carrageenin-induced rat paw oedema
      after oral administration of 0.1 mM x kg(-1); nevertheless introduction of an
      alkyl chain, leading to alkanamides 16-18, induced moderate to high activity: 46
      95% inhibition. The efficacy of these compounds in the inhibition of topical
      inflammation was confirmed by measuring reduction of ear thickness in the acute
      tetradecanoyl phorbol acetate (TPA)-induced mouse ear swelling assay. Preliminary
      pharmacomodulation brought to the fore that toxic effects induced, at 0.4 mM x
      kg(-1), by N-(pyridin-4-yl)(indol-3-yl)propanamide (17) could be attenuated or
      suppressed by 5-fluorination or introduction of a methoxycarbonylborane moiety,
      leading to 18 and 21.

PMID- 11525846
TI  - Synthesis of quinolinyl chalcones and evaluation of their antimalarial activity.
AB  - Quinolinyl chalcones were synthesized and evaluated for their inhibition of the
      Plasmodium falciparum cystein protease falcipain and their activity against
      cultured P. falciparum parasites. They were also tested for in vivo efficacy in a
      rodent P. berghei model. Their activity against falcipain and as antimalarials
      was moderate, but antimalarial activity was probably not due to the inhibition of
      falcipain and may follow a different mechanism. 1-(2,4-Dichlorophenyl)-3-[3-(2
      chloro-6,7-dimethoxiquinolinyl)]-2-propen-1-one 3j was the most promising
      compound among those here reported (IC50 19.0 microM).

PMID- 11525847
TI  - Synthesis and biological evaluation of O-alkylated tropolones and related alpha
      ketohydroxy derivatives as ribonucleotide reductase inhibitors.
AB  - A series of O-alkylated tropolones and related alpha-ketohydroxy compounds were
      evaluated for their biological activities and were shown to present an expected
      ribonucleotide reductase inhibition and cytotoxicity against some cancer cell
      lines but no antitubulin activity. Pharmacomodulation studies were realised to
      understand and enhance the observed activities. These original benzylic,
      heterocyclic and allylic compounds have been synthesised by a phase-transfer
      catalysed O-alkylation developed in our laboratories.

PMID- 11525848
TI  - 2-arylalkyl-substituted anthracenones as inhibitors of 12-lipoxygenase enzymes.
      1. Structure-activity relationships of the terminal aryl ring.
AB  - A series of 2-arylmethyl-substituted anthracenones were synthesized and tested as
      inhibitors of three types of 12-lipoxygenase isoforms in epidermal homogenate of
      mice, bovine platelets and porcine leucocytes. Their inhibitory activities were
      compared with those to inhibit the 5-lipoxygenase enzyme in bovine leucocytes.
      Structure-activity relationships are described with particular emphasis on
      modifications of the terminal aryl nucleus. The ability of the compounds to
      selectively inhibit the 12-lipoxygenase enzymes was dependent on a high overall
      lipophilicity of the inhibitor, whereas compounds with decreased lipophilicity
      were also inhibitors of the 5-LO enzyme. Among the more lipophilic inhibitors,
      the unsubstituted 2-phenylmethyl analogue 6a as well as the carboxylic acid ester
      6q appeared to be selective inhibitors of platelet-type 12-LO isoform.

PMID- 11525849
TI  - Measurement of depth of burns by laser Doppler perfusion imaging.
AB  - Laser Doppler perfusion imaging (LDPI), is a further development in laser Doppler
      flowmetry (LDF). Its advantage is that it enables assessment of microvascular
      blood flow in a predefined skin area rather than, as for LDF, in one place. In
      many ways this method seems to be more promising than LDF in the assessment of
      burn wounds. However, several methodological issues that are inherent in the LDPI
      technique, and are relevant for the assessment of burn depth, must be clarified.
      These include the effect of scanning distance, curvature of the tissue, thickness
      of topical wound dressings, and pathophysiological effects of skin colour,
      blisters, and wound fluids. Furthermore, we soon realised that to examine the
      perfusion image generated by LDPI adequately the process of analysis was
      appreciably improved by the simultaneous use of digital photography. In the
      present investigation we used both in vitro and in vivo models and also examined
      burned patients, and found that the listed factors all significantly affected the
      LDPI output signal. However, if these factors are known to the examiner, most of
      them can be adjusted for. If the technique is further improved by minimizing such
      effects and by reducing the practical difficulties of applying it to a burned
      patient in the burns unit, the technique may find uses in everyday clinical
      decision-making.

PMID- 11525850
TI  - Elevation of plasma free PAI-1 levels as an integrated endothelial response to
      severe burns.
AB  - To clarify the role of plasminogen activator inhibitor type 1 (PAI-1) in postburn
      hypercoagulation, we assayed the plasma levels of tissue-type plasminogen
      activator (t-PA) antigen, total PAI-1 antigen, and total t-PA-PAI-1 complex in 15
      burned patients. The total body surface area of the burn injury ranged from 30 to
      80%. Serial blood samples were collected from 12 to 168 h following the thermal
      injury. The plasma t-PA level and the free PAI-1 level increased significantly in
      the immediate postburn period, and the percent increase in the latter over the
      values in the healthy controls was much greater than that of the former. The
      ratio of the concentrations of t-PA-PAI-1 complex to free PAI-1 decreased
      throughout the 7 postburn days. The fact that the decreases in this ratio clearly
      showed no dissociation of the euglobulin fraction suggests that the postburn
      hypofibrinolysis occurred as a result of increased synthesis of PAI-1. On the
      other hand, changes in several parameters of the coagulation or fibrinolysis
      system and in plasma thrombomodulin showed that postburn hypercoagulability is
      associated with secondary hyperfibrinolysis with no evidence of vascular
      endothelial injury. The paradoxical coexistence of postburn hyper- and
      hypofibrinolysis is a good reflection of the character of PAI-1, which is a
      biphasic protein that is both a functional protein and an acute phase reactant.
      Thus, increased synthesis of PAI-1 may not enhance postburn hypercoagulability to
      create a coagulation-dominant type of disseminated intravascular coagulation
      severe enough to trigger multiple organ dysfunction syndrome. In conclusion,
      increased synthesis of PAI-1 in the initial postburn period reflects an
      integrated endothelial response to burn stress, and because it is a functional
      protein, the concentration of free PAI-1 antigen may be an important index for
      predicting secondary consumption coagulopathy.

PMID- 11525851
TI  - Characteristics of plasma extracellular SOD in burned patients.
AB  - The aim of this study was to examine three types of superoxide dismutase (SOD) in
      plasma after burns, and especially to clarify the characteristics of plasma
      extracellular SOD (EC-SOD) in burned patients. A total of 71 blood samples were
      collected from 18 patients on arrival, day 1, day 3 and day 5 after burns. We
      measured three types of SOD (Mn, Cu/Zn, EC) in plasma using ELISA, and the
      relationships among the three types of SOD concentrations were examined. We next
      analyzed the characteristics of plasma EC-SOD using stepwise multivariate
      regression analysis. Any plasma SOD isoenzyme concentration measured after burns
      was beyond the normal range and EC-SOD accounted for the major part of plasma
      SODs. EC-SOD and Cu/Zn-SOD were positively correlated, whereas Mn-SOD was not
      related to the other SODs. Also, plasma EC-SOD was significantly related to
      existence of inhalation injury, %TBSA and age, respectively. The plasma EC-SOD
      might therefore play some roles in the pathophysiology of burned patients.

PMID- 11525852
TI  - Predicting survival in an elderly burn patient population.
AB  - The purpose of this study was to analyze the outcome of elderly burn victims and
      to determine an instrument to predict survival in this population. Charts of
      three hundred and eight burn patients > or =60 yr of age who were admitted to a
      university-based hospital between the years of 1977-1996 were retrospectively
      analyzed. The mean age of the population was 71.5+/-8.6, with a male predominance
      (1.8 to 1, P < 0.001). The majority of the burns were secondary to flame injuries
      (210, 68.6%). The median body surface area (BSAB) was 13.0% with an in-hospital
      mortality rate of 30.2%. We demonstrated improved survival in patients aged 60-74
      yr as compared to 1965-1971 national burn survival data. A similar trend could
      not be shown in the very old (> 75 yr of age). Only age and BSAB were related to
      death by multiple stepwise forward linear regression. The Baux score, which adds
      age and BSAB, was predictive of outcome in 87.0% of our population. In
      conclusion, this study reinforces the high mortality associated with burn
      injuries in the elderly and the superior ability of the Baux score (age + percent
      burn) in predicting outcome in this population.

PMID- 11525853
TI  - The influence of body mass index on burn surface area estimated from the area of
      the hand.
AB  - It is well recognised that initial estimates of the area involved in a burn
      injury by inexperienced clinicians are frequently excessive. In Britain the
      palmar surface area of the hand is taught to approximate 1% of the total body
      surface area (TBSA), but no allowance is made for variations in individual body
      weight. This study aimed to evaluate the relationship between hand surface area
      (HSA) and body mass index (BMI) using healthy volunteers. We found that mean HSA
      diminished significantly as BMI increased in both sexes (P<0.001). This effect
      was, however, more pronounced in women, particularly those with a BMI greater
      than 31 kg/m(2) in whom the HSA represented only 0.64%. Awareness of the
      potential for over-estimation of burn surface area using this method alone may
      improve the accuracy of burn area estimation and consequent need for commencing
      resuscitation.

PMID- 11525854
TI  - Bacteriology of burn wounds--the first three years in a new burn unit at the
      Medical College Chandigarh.
AB  - A retrospective study was conducted at Government Medical College and Hospital,
      Chandigarh to analyse the bacterial isolates from the wounds of patients admitted
      to the Burns Unit and to determine the sensitivity pattern of the commonly
      cultured organisms over a 3-year period from May 1997 to May 2000. A total of 336
      samples were analysed, with 293 positive samples yielding 324 isolates. The
      isolates obtained from the culture of wound swabs were single in the majority of
      cases (78.0%). Pseudomonas was the most commonly cultured organism (54.2%)
      followed by Staphylococcus aureus (20.8%). Isolation of other organisms was
      uncommon by comparison. No isolates of beta-hemolytic streptococci or diptheroids
      were encountered.

PMID- 11525855
TI  - Usage of autograft and allograft skin in treatment of burns in children.
AB  - Large burns still present problems regarding the availability of enough
      autologous skin cover. The two Units have no experience in using cultured
      keratinocytes as a substitute for split skin grafts, as these are not available
      in the Kingdom of Saudi Arabia and are therefore not practical. At the same time,
      we have been obliged to abandon the use of human allograft skin from cadavers and
      other patients, because it is not acceptable in our culture. Our favoured method
      for resurfacing large burn areas in children is to use widely meshed autologous
      skin, overlaid with meshed allograft from a parent (to minimise the risk of HIV
      transmission). We report our experience using this technique in five children.
      The fate of the intermingled grafts has been followed clinically, and in some
      cases histologically. There has been long-term persistence of the parental skin
      without rejection and although allograft dermis appears to contribute to the
      final cover, the cellular elements of the parental skin apparently do not
      survive.

PMID- 11525856
TI  - Free flaps in burn reconstruction.
AB  - In this paper, we present our experience of free flap reconstructions in burned
      patients. It allows the preservation of otherwise unsalvageable deep burn
      injuries and secondary correction of contracted burn scars. We analyse the
      indications of different free flaps, according to different anatomic regions and
      defects: depth and width of the loss of tissue, different colour skin, texture
      and thickness of the receptor area, weight-bearing or not weight-bearing surface.
      Free flap reconstructions were successful in 50 of 53 cases (94%). They provide
      good aesthetic and functional results with low morbidity both in acute deep burn
      injuries as in delayed reconstructions.

PMID- 11525857
TI  - Distant pedicle flaps for soft tissue coverage of severely burned hands: an old
      idea revisited.
AB  - Burns to the hand that are complicated by exposure of bone, joint or tendon
      cannot be closed with conventional skin grafts and require flap procedures to
      prevent further damage. Local or regional flaps may be unavailable if electrical
      or blast trauma produces a large zone of injury, or when forearm burn injury
      extends beyond fascia. Free tissue transfer may not be tolerated by critically
      ill burn patients. In these circumstances, distant pedicle flaps are one option
      for safe and effective soft tissue coverage. Over a 5-year period, we have
      performed six distal pedicle flaps for coverage of exposed hand structures when
      local or free flaps were contraindicated or unavailable. The patients required an
      average of 4.5 surgical procedures to complete hand reconstruction and soft
      tissue coverage. Soft tissue coverage was completely successful in five patients
      and partially successful in one patient. Single stage local or free flaps remain
      the treatment of choice when burned hands cannot be covered with skin grafts.
      When these flap options are not available, distant pedicle flaps provide a safe
      alternative.

PMID- 11525858
TI  - The use of silver coated dressings on donor site wounds: a prospective,
      controlled matched pair study.
AB  - Acticoat, a new silver-coated dressing, produces a moist healing environment
      along with the sustained release of ionic silver for improved microbial control.
      These properties suggest that Acticoat might be a useful donor site dressing.
      However, there are no human studies which assess Acticoat for this use. The
      purpose of this study was to compare the healing of human skin graft donor sites
      dressed with Acticoat, to the healing of those dressed with Allevyn, an occlusive
      moist-healing environment material, which is our standard donor site dressing. In
      burn patients who had undergone burn excision and grafting, identical side-by
      side split thickness donor site wound pairs were dressed with Allevyn and
      Acticoat. Re-epithelialization was directly assessed daily by a single observer
      from post-operative day 6 onward, and by four independent observers who rated the
      extent of re-epithelialization by viewing standardized digital images of the
      wounds that had been obtained on post-operative days 6, 8, 10,and 12. Donor sites
      were swabbed for bacterial culture on days 3, 6, and 9. Subsequently, each study
      donor site scar was rated by a blinded observer using the Vancouver Scar Scale at
      1, 2, and 3 months. Sixteen paired sites in 15 patients (3 female, 12 male) were
      studied. Donor sites dressed with Allevyn were >90% re-epithelialized at a mean
      of 9.1+/-1.6 days while donor sites dressed with Acticoat required a mean of
      14.5+/-6.7 days to achieve >90% re-epithelialization (P=0.004). The Allevyn sites
      had significantly greater estimated re-epithelialization at days 6, 8, 10 and 12
      than the Acticoat sites based on the observations of the digital images. There
      were no significant differences in the incidence of positive bacterial cultures
      with either dressing at days 3, 6, and 9. Donor sites dressed with Acticoat had
      significantly worse scars at 1 and 2 months but this difference resolved by 3
      months. Our findings do not support the use of Acticoat as a skin graft donor
      site dressing.

PMID- 11525859
TI  - Isolated buttock burns: epidemiology and management.
AB  - This is a retrospective study of the epidemiology and management of isolated
      buttock burns presenting to the Welsh Regional Burns Centre from January 1996 to
      December 1999. A total of 36 cases have been treated of which 31 are included in
      this study. Approximately, 50% are in the paediatric age group and the sex
      distribution is equal for both adults and children. Contact burns form the
      largest group, and in children resulted in superficial burns requiring dressings
      only. The adult population is more likely to sustain deeper burns that require
      skin grafting, and approximately 50% will have a contributing premorbid
      condition. Despite difficulties in dressing and positioning of the patients,
      grafting of full thickness burns is appropriate without recourse to faecal
      diversion.

PMID- 11525860
TI  - Partial liquid ventilation with perfluorocarbons for treatment of ARDS in burns.
AB  - Pulmonary failure remains the major determinant of mortality and morbidity
      following burn injury. We hypothesized that intratracheal instillation of
      perfluorocarbon liquids could be a therapeutic measure in combination with
      conventional mechanical ventilation to improve pulmonary gas exchange in acute
      respiratory distress syndrome with thermal injury. Forty-five New Zealand rabbits
      were used for this prospective and randomized experimental study. The animals
      were burned by scald to reach full-thickness 40% burn surface area. After
      inducing respiratory distress by repeated lung lavage with saline, animals were
      divided randomly into three groups of 15 rabbits each. First group (control
      group) received conventional treatment (continuous positive-pressure ventilation)
      using a FiO(2) of 1.0, tidal volume of 12 ml/kg, respiratory frequency of 30
      cycles/min and PEEP of 6 cm H(2)O. Second group was treated with 9 ml/kg of
      intratracheal perfluorocarbon. Third group was treated with 15 ml/kg of
      intratracheal perfluorocarbon. All groups were ventilated for 6 h. In the
      perfluorocarbon groups, PaO(2) increased significantly (P<0.05) from 46+/-4 to
      439+/-10 mmHg compared to the control group in a dose-related manner. In
      pulmonary parameters we observed significant (P<0.05) decrease in mean airway
      pressures from the pre-treatment value of 11.44+/-0.15 cm H(2)O to the post
      treatment 10.22+/-0.12 cm H(2)O and increase (P<0.05) in respiratory system
      compliance from 1.8+/-0.02 to 2.46+/-0.07 ml/cm H(2)O with the perfluorocarbon.
      Perfluorocarbon instillation did not result in statistically significant changes
      in arterial pressure, heart rate and central venous pressure. In conclusion,
      partial liquid ventilation with perfluorocarbon is a new technique leading to a
      marked and sustained improvement in oxygenation and pulmonary function in an
      experimental model of ARDS in burns.

PMID- 11525861
TI  - Intraoperative positioning for circumferential extremity burns.
AB  - A technique for intra-operative patient positioning is described which allows
      circumferential access to burned extremities for prepping and surgery. This
      technique avoids the need for turning the patient during the operative procedure.
      In our 13 yr experience, there have been no complications attributed to this
      technique.

PMID- 11525862
TI  - Clonus: an unusual delayed neurological complication in electrical burn injury.
AB  - Patients surviving high-voltage electrical injury may have early and delayed
      sequelae. The most apparent neurological complications are known to be cerebral
      injury, spinal cord lesions, peripheral-nerve injuries and motor neuropathies. In
      this study, clonus, which is an unusual late neurological sequela in an
      electrical burn patient and presented as series of rhythmic, monophasic
      contractions and relaxations of a group of muscles, is presented. Possible
      mechanisms of this unusual late sequela and the clinical outcome of the patient
      are discussed. Ankle and patellar clonus was observed in 4 patients and uvular
      clonus in 1 patient. Clonus started 3 weeks following the injury in our patients
      and disappeared over a period of 1 yr in 2 patients, and did not disappear in the
      remaining 2 patients. In the current literature, this is the first report, which
      presents an unusual sequela following electrical injury. Clonus should also be
      considered a specific type of neurological sequela following high- or super
      voltage electric injury. This may help to inform the patients in the postinjury
      period and to improve the efficacy of the rehabilitation of the victims.

PMID- 11525863
TI  - Treatment of drug-induced toxic epidermal necrolysis (Lyell's syndrome) with
      intravenous human immunoglobulins.
AB  - Toxic epidermal necrolysis (TEN) is a rare drug-induced life-threatening disease.
      Currently, the disease is only treated by supportive and antiseptic measures.
      Quite recently intravenous immunoglobulins (IG) were shown to be a promising TEN
      treatment. The rationale for their use is based on the fact that keratinocyte
      apoptosis in TEN involves the CD95 (APO-1/Fas) cell surface receptor-ligand
      system. We successfully treated a TEN patient with high dose of intravenous IG.
      The clinical recovery appeared exceptionally rapid. Immunohistochemistry showed
      that the IG action probably developed on the CD95 receptor-ligand system at the
      keratinocytes surface.

PMID- 11525864
TI  - Fungal endocarditis in a paediatric burns patient.

PMID- 11525865
TI  - Adrenal hemorrhage in a pediatric burn patient.
AB  - Adrenal hemorrhage with subsequent insufficiency is a rare complication in the
      burn patient. The case of a previously healthy 3-year-old Latin American male who
      was a victim of child abuse is presented. He suffered a submersion injury in hot
      water leading to a 45% total body surface area burn. An acute deterioration on
      the 7th post burn day was unresponsive to standard inotropic support and
      cardiopulmonary resuscitation. Post mortem examination revealed bilateral adrenal
      hemorrhage that had not been present 2 days earlier. To the authors' knowledge,
      this is the first reported case in a pediatric burn patient. The clinical
      manifestations of adrenal insufficiency vary widely and can be easily confused
      with sepsis. High index of suspicion is necessary for early diagnosis and
      treatment. Serum cortisol level should be checked and steroid therapy implemented
      if sepsis syndrome is unresponsive to standard therapy in this setting. This
      early intervention may be the key to improved survival of the burn patient with a
      sudden unexplained deterioration resistant to well established resuscitation
      methods.

PMID- 11525866
TI  - Medical treatment of a central vein suppurative thrombosis with cerebral
      metastatic abscesses in a burned child.
AB  - A 2-year-old girl admitted with third degree burns (35% TBSA) received 7 weeks
      poly-antibiotic therapy combined with heparin for a severe Methicillin-resistant
      Staphylococcus aureus sepsis with multiple metastatic abscesses (lung, skin,
      brain), from a suppurative thrombophlebitis of the right jugularis interna,
      extended to the axillary and cava superior veins. Surgical treatment was
      contraindicated by the local extension. The child was discharged without major
      neurological sequelae 3 months after admission.

PMID- 11525867
TI  - Partial growth plate fusion caused by burn.
AB  - Growth plate fusion is a rare but important complication of burn injury in
      childhood. Reported cases are all of complete fusion. We present a case of
      partial fusion of the growth plates secondary to a burn injury, which to our
      knowledge has not been reported in the literature before. Partial fusion of the
      growth plate behaves differently as compared with complete fusion, and if treated
      at an early stage by appropriate surgery limb deformity and long-term disability
      may be prevented. The importance of early recognition and treatment cannot be
      overemphasized.

PMID- 11525868
TI  - Lipid peroxidation in aging and age-dependent diseases.
AB  - Aging is related with an increase in oxidation products derived from nucleic
      acids, sugars, sterols and lipids. Evidence will be presented that these
      different oxidation products are generated by processes induced by changes in the
      cell membrane structure (CMS), and not by superoxide, as commonly assumed. CMS
      activate apparently membrane bound phospholipases A2 in mammals and plants. Such
      changes occur by proliferation, aging and especially by wounding. After
      activation of phospholipases, influx of Ca2+ ions and activation of lipoxygenases
      (LOX) is induced. The LOX transform polyunsaturated fatty acids (PUFAs) into
      lipid hydroperoxides (LOOHs), which seem to be decomposed by action of enzymes to
      signalling compounds. Following severe cell injury, LOX commit suicide. Their
      suicide liberates iron ions that induce nonenzymic lipid peroxidation (LPO)
      processes by generation of radicals. Radicals attack all compounds with the
      structural element -CH=CH-CH(2)-CH=CH-. Thus, they act on all PUFAs independently
      either in free or conjugated form. The most abundant LPO products are derived
      from linoleic acid. Radicals induce generation of peroxyl radicals, which oxidise
      a great variety of biological compounds including proteins and nucleic acids.
      Nonenzymic LPO processes are induced artificially by the treatment of pure PUFAs
      with bivalent metal ions. The products are separable after appropriate
      derivatisation by gas chromatography (GC). They are identified by electron impact
      mass spectrometry (EI/MS). The complete spectrum of LPO products obtained by
      artificial LPO of linoleic acid is detectable after wounding of tissue, in aged
      individuals and in patients suffering from age-dependent diseases. Genesis of
      different LPO products derived from linoleic acid will be discussed in detail.
      Some of the LPO products are of high chemical reactivity and therefore escape
      detection in biological surrounding. For instance, epoxides and highly
      unsaturated aldehydic compounds that apparently induce apoptosis.

PMID- 11525869
TI  - Free radicals associated with DNA damage.
AB  - This short review focuses on the chemical events related to DNA damage induced by
      free radicals. Diffusible hydroxyl radicals (HO) are able to react with either
      the sugar units by hydrogen abstraction or with the base moieties by addition.
      Selectively generated carbon-centred radicals at C1', C4' and C5' in model
      nucleosides or oligonucleotides and their subsequent fate under aerobic or anoxic
      condition are discussed by rationalisation of the available kinetic data.
      Reaction paths for the formation of nucleobase modifications such as 8-oxoG and
      FapyG, amplification of base damage, and tandem lesions are also discussed. Some
      types of DNA damage may be poorly repaired leading to deleterious genetic changes
      with time.

PMID- 11525870
TI  - Lipid hydroperoxide-mediated DNA damage.
AB  - Lipid hydroperoxides are formed in vivo through free radical pathways from the
      action of reactive oxygen species on polyunsaturated fatty acids. They are also
      formed as specific products of lipoxygenases and cyclooxygenases. Homolytic
      decomposition of lipid hydroperoxides to the alpha,beta-unsaturated aldehyde
      genotoxins, 4-oxo-2-nonenal, 4,5-epoxy-2(E)-decenal, and 4-hydroxy-2-nonenal
      occurs through two quite distinct pathways. One pathway involves a complex
      rearrangement of the alkoxy radical derived from the lipid hydroperoxide and the
      other pathway involves the intermediate formation of another potential genotoxin,
      4-hydroperoxy-2-nonenal. 4,5-Epoxy-2(E)-decenal forms the unsubstituted etheno-2
      deoxyadenosine adduct with DNA, a mutagenic lesion which has been observed in
      human tissue DNA samples. Several new ethano- and etheno-DNA-adducts have been
      identified from the reaction of 4-oxo-2-nonenal with DNA. 4-Hydroxy-2-nonenal
      forms propano adducts with 2'-deoxyguanosine. It can also up-regulate
      cyclooxygenase-2 expression. As cyclooxygenase-2 converts linoleic acid into
      lipid hydroperoxides, this provides a potential mechanism for increased
      production of genotoxic bifunctional electrophiles. Malondialdehyde (beta-hydroxy
      acrolein), another genotoxic bifunctional electrophile, is formed during
      homolytic decomposition of lipid hydroperoxides that contain more than two double
      bonds. Other sources of malondialdehyde include, hydroxyl radical-mediated
      decomposition of the 2'-deoxyribose DNA backbone and formation as a side-product
      during the biosynthesis of thromboxane A(2). Malondialdehyde reacts with DNA to
      form primarily a propano adduct with 2'-deoxyguanosine (M(1)G-dR). Significant
      advances in the characterization and analysis of lipid hydroperoxide-derived
      endogenous DNA-adducts have been made over the last decade so that dosimetry
      studies of human populations are now possible. Such studies will help elucidate
      the role of lipid hydroperoxide-derived endogenous DNA as mediators of cancer,

PMID- 11525871
TI  - Imaging techniques used for the detection of 8-oxoguanine adducts and DNA repair
      proteins in cells and tissues.
AB  - The presence of 8-oxoguanine (8-oxoG) in DNA is considered a marker of oxidative
      stress and DNA damage. Numerous biochemical techniques have been described for
      its detection in cells or tissues. Although these approaches are quantitative,
      they do not provide insights into whether the lesion occurs in mitochrondrial
      versus genomic DNA. In addition, biochemical techniques are not amenable to the
      evaluation of individual cells or archival tissues. Antibodies have been raised
      against 8-oxoG, which may circumvent some of these issues. In this review, we
      described the use of in situ imaging techniques to detect oxidative DNA damage
      including the comet assay. We will review our previous work that describes the
      utility of an antibody fragment (Fab) engineered to recognize 8-oxoG in DNA.
      Furthermore, we will discuss the analysis of DNA repair enzymes in the assessment
      of oxidative DNA damage. Finally, advantages and potential concerns associated
      with immunodetection of 8-oxoG are discussed.

PMID- 11525872
TI  - Oxidative modification of proteins during aging.
AB  - Accumulating experimental evidence supports the proposal that many of the changes
      which occur during aging are a consequence of oxidative damage. Reactive oxygen
      species react with all three of the major cellular macromolecules, nucleic acids,
      lipids, and proteins. This minireview focuses on proteins as targets of oxidizing
      species during aging. Many of the reactions mediated by these oxidizing species
      result in the introduction of carbonyl groups into proteins. The steady-state
      level of carbonyl-bearing proteins increases exponentially during the last third
      of lifespan in animals ranging from C. elegans to man. Genetic and non-genetic
      manipulations which lengthen lifespan cause a decrease in the level of protein
      carbonyl while those which shorten lifespan increase the level. Oxidized proteins
      bearing carbonyl groups are generally dysfunctional, and in the last third of
      lifespan the content of these oxidized proteins rises to a level likely to cause
      substantial disruption of cellular function.

PMID- 11525873
TI  - Protein oxidation and ageing.
AB  - Organisms produce reactive oxygen species (ROS) throughout their lives. The
      activities of a number of key antioxidant enzymes, such as catalase, superoxide
      dismutase and glutathione peroxidase, which protect against the damaging effects
      of ROS, have been reported to decrease with increasing age, though this is not
      unequivocal. In contrast, sacrificial antioxidants such as ascorbate, thiols and
      tocopherol do not appear to decrease with increasing age. It is also possible
      that ROS production increases with age as a result of poorer coupling of electron
      transport components, and an increased level of redox-active metal ions that
      could catalyse oxidant formation. As a result of this decrease in antioxidant
      defences, and increased rate of ROS formation, it is possible that the impact of
      ROS increases with age. ROS are known to oxidise biological macromolecules, with
      proteins an important target. If the argument that the impact of ROS increases
      with age is true, then proteins would be expected to accumulate oxidised
      materials with age, and the rate of such accumulation should increase with time,
      reflecting impaired inefficiency of homeostasis. Here we review the evidence for
      the accumulation of oxidised, or modified, extra- and intra-cellular proteins in
      vivo.

PMID- 11525874
TI  - Aging and oxidation of reactive protein sulfhydryls.
AB  - Protein sulfhydryls are potential sites of reversible oxidative modification by S
      glutathiolation, and S-nitrosylation, but they are also susceptible to
      irreversible damage by oxidative conditions. In the absence of adequate
      antioxidant protection, these reactive sites may become useless because of this
      irreversible damage. It has recently become possible to directly access the
      nature and amount of irreversibly oxidized protein sulfhydryls by both gel-based
      methods and direct amino acid analysis. Results are in keeping with the concept
      that irreversible oxidation of protein sulfhydryls is more extensive in aged
      tissue samples. It is proposed that an adequate pool of glutathione is essential
      to prevent this increase in sulfhdryl oxidation. The increased amount of protein
      sulfhydryl damage may be critically important to the function of signal
      transduction and transcription events that utilize proteins containing these
      reactive sites.

PMID- 11525875
TI  - The role of AGEs in aging: causation or correlation.
AB  - Over a dozen advanced glycation end-products (AGEs) have been identified in
      tissue proteins by chemical or immunological methods. Of these, about half are
      known to accumulate with age in collagen at a rate that correlates with the half
      life of the collagen. AGEs may be formed by oxidative and non-oxidative reactions
      and are in some cases identical to advanced lipoxidation end-products (ALEs)
      formed in protein during lipid peroxidation reactions. AGEs affect the
      biochemical and physical properties of proteins and the extracellular matrix
      (ECM), including the charge, hydrophobicity, turnover and elasticity of collagen,
      and the cell adhesion, permeability and pro-inflammatory properties of the ECM. A
      number of scavenger and AGE-specific receptors have been identified that may
      mediate the turnover of AGE-proteins, catalyze the local production of reactive
      oxygen species and attract and activate tissue macrophages. Although AGEs in
      proteins are probably correlative, rather than causative, with respect to aging,
      they accumulate to high levels in tissues in age-related chronic diseases, such
      as atherosclerosis, diabetes, arthritis and neurodegenerative disease. Inhibition
      of AGE formation in these diseases may limit oxidative and inflammatory damage in
      tissues, retarding the progression of pathophysiology and improve the quality of
      life during aging.

PMID- 11525876
TI  - Oxidative stress and protein aggregation during biological aging.
AB  - Biological aging is a fundamental process that represents the major risk factor
      with respect to the development of cancer, neurodegenerative, and cardiovascular
      diseases in vertebrates. It is, therefore, evident that the molecular mechanisms
      of aging are fundamental to understand many disease processes. In this regard,
      the oxidation and nitration of intracellular proteins and the formation of
      protein aggregates have been suggested to underlie the loss of cellular function
      and the reduced ability of senescent animals to withstand physiological stresses.
      Since oxidatively modified proteins are thermodynamically unstable and assume
      partially unfolded tertiary structures that readily form aggregates, it is likely
      that oxidized proteins are intermediates in the formation of amyloid fibrils. It
      is, therefore, of interest to identify oxidatively sensitive protein targets that
      may play a protective role through their ability to down-regulate energy
      metabolism and the consequent generation of reactive oxygen species (ROS). In
      this respect, the maintenance of cellular calcium gradients represents a major
      energetic expense, which links alterations in intracellular calcium levels to ATP
      utilization and the associated generation of ROS through respiratory control
      mechanisms. The selective oxidation or nitration of the calcium regulatory
      proteins calmodulin and Ca-ATPase that occurs in vivo during aging and under
      conditions of oxidative stress may represent an adaptive response to oxidative
      stress that functions to down-regulate energy metabolism and the associated
      generation of ROS. Since these calcium regulatory proteins are also
      preferentially oxidized or nitrated under in vitro conditions, these results
      suggest an enhanced sensitivity of these critical calcium regulatory proteins,
      which modulate signal transduction processes and intracellular energy metabolism,
      to conditions of oxidative stress. Thus, the selective oxidation of critical
      signal transduction proteins probably represents a regulatory mechanism that
      functions to minimize the generation of ROS through respiratory control
      mechanisms. The reduction of the rate of ROS generation, in turn, will promote
      cellular survival under conditions of oxidative stress, when reactive oxygen and
      nitrogen species overwhelm cellular antioxidant defense systems, by minimizing
      the non-selective oxidation of a range of biomolecules. Since protein aggregation
      occurs if protein repair and degradative systems are unable to act upon oxidized
      proteins and restore cellular function, the reduction of the oxidative load on
      the cell by the down-regulation of the electron transport chain functions to
      minimize protein aggregation. Thus, ROS function as signaling molecules that fine
      tune cellular metabolism through the selective oxidation or nitration of calcium
      regulatory proteins in order to minimize wide-spread oxidative damage and protein
      aggregation. Oxidative damage to cellular proteins, the loss of calcium
      homeostasis and protein aggregation contribute to the formation of amyloid
      deposits that accumulate during biological aging. Critical to understand the
      relationship between these processes and biological aging is the identification
      of oxidatively sensitive proteins that modulate energy utilization and the
      associated generation of ROS. In this latter respect, oxidative modifications to
      the calcium regulatory proteins calmodulin (CaM) and the sarco/endoplasmic
      reticulum Ca-ATPase (SERCA) function to down-regulate ATP utilization and the
      associated generation of ROS associated with replenishing intracellular ATP
      through oxidative phosphorylation. Reductions in the rate of ROS generation, in
      turn, will minimize protein oxidation and facilitate intracellular repair and
      degradative systems that function to eliminate damaged and partially unfolded
      proteins. Since the rates of protein repair or degradation compete with the rate
      of protein aggregation, the modulation of intracellular calcium concentrations
      and energy metabolism through the selective oxidation or nitration of critical
      signal transduction proteins (i.e. CaM or SERCA) is thought to maintain cellular
      function by minimizing protein aggregation and amyloid formation. Age-dependent
      increases in the rate of ROS generation or declines in cellular repair or
      degradation mechanisms will increase the oxidative load on the cell, resulting in
      corresponding increases in the concentrations of oxidized proteins and the
      associated formation of amyloid.

PMID- 11525877
TI  - Age-dependent deamidation of asparagine residues in proteins.
AB  - Nonenzymatic deamidation of peptides and proteins represents an important
      degradation reaction occurring in vitro in the course of isolation or storage and
      in vivo during development and/or aging of cells. This review first presents a
      synopsis of the influence of structure on deamidation reaction proceeding via a
      five-membered succinimide intermediate, followed by an outline of procedures for
      separation and detection of deamidated forms. Selected examples for in vitro and
      in vivo deamidation are reviewed including the possible biological consequences
      of this protein degradation. Finally, the reaction of protein methyltransferase
      with L-isoaspartyl- and D-aspartyl residues and its possible role in protein
      repair is elucidated.

PMID- 11525878
TI  - Really old-palaeoimmunology: immunohistochemical analysis of extracellular matrix
      proteins in historic and pre-historic material.
AB  - In this review, we summarize data concerning the respective preservation and
      deterioration of antigenic determinants of various collagenous and non
      collagenous extracellular matrix (ECM) proteins in palaeontologic material of
      different ages. ECM proteins are the major quantitative constituents of mammalian
      organisms and were, therefore, selected as important representative proteins for
      these analyses. The specimens, studied by immunofluorescence and
      immunohistochemical techniques, included the skin of 500-1500 year-old human
      mummies from Peru, skin and striated muscle from the 5300-year-old glacier mummy
      ("Iceman") from Tyrol, Austria, and a 50-million-year-old bat with preserved soft
      body parts from the fossil excavation site of Messel, Germany. In frozen sections
      of the former two sources, epitopes recognized by specific antibodies for triple
      helical antigenic determinants of different types of collagen resistant against
      conventional proteases were preserved, while non-helical domains, as well as the
      non-collagenous ECM proteins, could no longer be demonstrated. The fossil bat,
      although showing evidence of fibrous, collagen-like structures in conventional
      histology, revealed no collagenous or non-collagenous ECM proteins by any
      technique. It later turned out that this was due to the replacement of the
      original soft parts in these fossils by lawns of bacteria. These studies
      introduced immunological techniques into palaeontology and opened new approaches
      for studying physiologically- and pathologically-altered structures in tissues of
      animals and humans of considerable historical age.

PMID- 11525879
TI  - Nitric oxide: biologic effects on muscle and role in muscle diseases.
AB  - Nitric oxide is a ubiquitous cell-signaling molecule involved in regulation of
      numerous homeostatic mechanisms and in mediation of tissue injury. Nitric oxide
      influences contraction, blood flow, and metabolism, as well as myogenesis. Nitric
      oxide exerts its influence by activation of guanylate cyclase and nitrosylation
      of proteins, which include glyceraldehyde-3-phosphate dehydrogenase, the
      ryanodine receptor and actomyosin ATPase. Skeletal muscle expresses all three
      isoforms of the nitric oxide synthase, including a muscle-specific splice
      variant; expression of the isoforms is fiber-type specific and influenced by age
      and disease. Nitric oxide produced with certain systemic conditions and local
      inflammation is likely toxic to skeletal muscle, either directly or in reactions
      with oxygen-derived radicals. Although nitric oxide impacts on many functions in
      muscle, its effects are subtle, and much work remains to be done to determine its
      importance in the pathogenesis of muscle diseases.

PMID- 11525880
TI  - Genetic characterization of a large, historically significant Utah kindred with
      facioscapulohumeral dystrophy.
AB  - In 1950, Tyler and Stephens reported a remarkable kindred affected with
      facioscapulohumeral dystrophy (FSHD), consisting of 1249 descendants of a man who
      emigrated to Utah in 1840. Members of this kindred are still seen in our clinic
      and, to our knowledge, no member had been tested for deletions at the FSHD1A
      locus on chromosome 4q35, the common chromosomal rearrangement associated with
      FSHD. We have identified 971 additional members of this kindred who either were
      not included in or unborn at the time of the report by Tyler and Stephens, and
      have identified 120 living members as affected by history or by examination.
      Members of this kindred contribute to a disease prevalence of nearly 1:15 000 in
      the Utah/southern Idaho region. We have demonstrated that affected members carry
      a disease-associated 20 kb deletion allele at the FSHD1A locus. This allele is
      the same size in multiple, distantly-related branches of the kindred, confirming
      the meiotic stability of the FSHD1A deletion. This large, genetically homogeneous
      population of patients represents a unique resource with which to study current
      questions about FSHD, including the possibilities of anticipation and parental
      transmission effects.

PMID- 11525881
TI  - Identification and functional characterization of a novel ryanodine receptor
      mutation causing malignant hyperthermia in North American and South American
      families.
AB  - Malignant hyperthermia is a pharmacogenetic disorder associated with mutations in
      Ca(2+) regulatory proteins. It manifests as a hypermetabolic crisis triggered by
      commonly used anesthetics. Malignant hyperthermia susceptibility is a dominantly
      inherited predisposition to malignant hyperthermia that can be diagnosed by using
      caffeine/halothane contracture tests. In a multigenerational North American
      family with a severe form of malignant hyperthermia that has caused four deaths,
      a novel RYR1 A2350T missense mutation was identified in all individuals testing
      positive for malignant hyperthermia susceptibility. The same A2350T mutation was
      identified in an Argentinean family with two known fatal MH reactions. Functional
      analysis in HEK-293 cells revealed an altered Ca(2+) dependence and increased
      caffeine sensitivity of the expressed mutant protein thus confirming the
      pathogenic potential of the RYR1 A2350T mutation.

PMID- 11525882
TI  - Congenital myopathy with central cores and fingerprint bodies in association with
      malignant hyperthermia susceptibility.
AB  - A 26-year-old man had proximal weakness in the shoulder and the pelvic girdle
      since infancy. His sister, aged 16 years, presented a similar phenotype with more
      pronounced pelvic weakness. His muscle biopsy showed dense non-reducing
      inclusions which had a lamellar pattern at the ultrastructural level. These
      structures showed the typical features of fingerprint inclusions which were
      widely distributed in the fibers. Several central cores and other structural
      changes such as Z-line streaming were also observed. In view of the central
      cores, the male patient was investigated for malignant hyperthermia
      susceptibility. After exposure to halothane or caffeine, unusual intense
      contractures were observed on fiber preparations. The coexistence of central
      cores associated with fingerprint inclusions is suggestive of mixed congenital
      myopathy, which is in our case associated with malignant hyperthermia
      susceptibility.

PMID- 11525883
TI  - A missense mutation in the exon 8 of lamin A/C gene in a Japanese case of
      autosomal dominant limb-girdle muscular dystrophy and cardiac conduction block.
AB  - A case of autosomal dominant limb-girdle muscular dystrophy with atrioventricular
      conduction block (LGMD1B) has been documented. In this family, 13 members, nine
      males and four females, had cardiac arrhythmia requiring pacemakers. The proband,
      a 67-year-old male, had longstanding proximal muscle weakness later associated
      with cardiac arrhythmia but showed neither rigid spine nor joint contracture. His
      muscle enzymes were within normal range and muscle biopsy showed myopathic
      changes. Gene analysis of the proband revealed Tyr481His mutation in the exon 8
      of lamin A/C (LMNA) gene which is adjacent to the codon mutated in reported cases
      of familial partial lipodystrophy. This is the first report of muscular dystrophy
      shown to have a mutation of LMNA in a Japanese family as well as the first case
      of missense mutation in the exon 8 with LGMD1B phenotype.

PMID- 11525884
TI  - Calpain 3 gene mutations: genetic and clinico-pathologic findings in limb-girdle
      muscular dystrophy.
AB  - Mutations in the calpain 3 gene have been proven to be responsible for limb
      girdle muscular dystrophy (LGMD) type 2A. To determine the incidence and
      genotypes of the calpain 3 (p94) gene mutations in Japanese LGMD patients, we
      sequenced the gene in 80 patients with clinical characteristics of autosomal
      recessive or sporadic LGMD. We identified 13 distinct pathogenic mutations in 21
      patients (26%), including seven missense mutations, four splice-site mutations
      and two insertions in which six were novel mutations. Among the 21 patients, 15
      (71%) had three types of the common missense (G233V, R461C, D707G) and one
      insertion (1795-1796insA) mutation. The patients had slowly progressive muscle
      weakness with age of onset of the disease varying from 6 to 52 years, averaging
      20.9. The most striking pathologic findings were the presence of lobulated fibers
      in 14 patients, especially in the advanced stages. Differing from Duchenne and
      Becker muscular dystrophy, opaque (hypercontracted) fibers were very rarely seen.
      These findings may be helpful in establishing diagnostic screening strategies in
      Japanese LGMD patients.

PMID- 11525885
TI  - Do immune cells promote the pathology of dystrophin-deficient myopathies?
AB  - Many features of dystrophin-deficient muscle pathology are not clearly related to
      the loss of mechanical support of the muscle membrane by dystrophin. In the
      present review, evidence that supports a role for the immune system in promoting
      the pathology of dystrophinopathy is presented. The findings summarized here
      indicate that specific, cellular immune responses by cytotoxic T-lymphocytes and
      helper T-lymphocytes contribute to muscle pathology in dystrophin-deficient
      muscle, and that removal of specific lymphoid cell populations can reduce muscle
      pathology. In addition, innate immune responses may also promote
      dystrophinopathies by the tremendous infiltration of myeloid cell populations
      into the dystrophic muscle. Loss of normal redox homeostasis by dystrophin
      deficient muscle may increase its sensitivity to free radical-mediated damage by
      myeloid cells. Collectively, the observations presented here suggest that the
      contribution of the immune system to dystrophinopathies may be significant, and
      that therapeutic approaches based upon immune interventions may ameliorate the
      pathological progression of dystrophin deficiency.

PMID- 11525886
TI  - Respiratory chain defects in hereditary spastic paraplegias.
AB  - Hereditary Spastic Paraplegias (HSPs) are heterogeneous neurodegenerative
      disorders whose etiopathogenesis is still unclear. The identification of
      pathogenic mutations in a gene (SPG7) encoding a mitochondrial metalloprotease
      suggested that oxidative phosphorylation (OXPHOS) alterations might underlie HSP
      in a subgroup of patients. We performed clinical, morphological, biochemical, and
      molecular genetic studies in six HSP patients and in six sporadic patients to
      investigate OXPHOS in muscle biopsies. Complicated and pure forms were included
      in our study. Morphological alterations of the type seen in OXPHOS-related
      disorders were found in three patients. Five patients showed an isolated defect
      of complex I activity. No mutations in the SPG7 gene were detected. Our results
      suggest that OXPHOS defects in HSP patients are more common than previously
      believed.

PMID- 11525887
TI  - Merosin-positive congenital muscular dystrophy with mental retardation,
      microcephaly and central nervous system abnormalities unlinked to the Fukuyama
      muscular dystrophy and muscular-eye-brain loci: report of three siblings.
AB  - Classical merosin (2 laminin)-positive congenital muscular dystrophy is a
      heterogeneous subgroup of disorders; a few cases characterized by severe mental
      retardation, brain involvement and no ocular abnormalities were called Fukuyama
      like congenital muscular dystrophy. We report a family of healthy non
      consanguineous parents, with four affected siblings, of which one died at the age
      of 7 months due to an intercurrent illness, who presented congenital hypotonia,
      severe mental retardation, microcephaly, delayed psychomotor development,
      generalized muscular wasting and weakness with mild facial involvement, calf
      pseudohypertrophy, joint contractures and areflexia. Muscle biopsy disclosed
      severe muscular dystrophy. Immunostaining for laminin 2 80 kDa and clone
      Mer3/22B2 monoclonal antibodies, 1 and 1 chain was preserved. Magnetic resonance
      imaging findings were consistent with pontocerebellar hypoplasia, bilateral
      opercular abnormalities and focal cortical dysplasia as well as minute
      periventricular white matter changes. Clusters of small T2-weighted focal
      hyperintensities in both cerebellar hemispheres consistent with cysts were
      observed in two of the three siblings studied with magnetic resonance imaging.
      Ophthalmologic and cardiologic examination was normal. Haplotype analysis using
      microsatellite markers excluded the Fukuyama congenital muscular dystrophy, LAMA2
      and muscle-eye-brain disease loci. Thus, a wider spectrum of phenotypes, gene
      defects and protein deficiencies might be involved in congenital muscular
      dystrophy with brain abnormalities.

PMID- 11525888
TI  - Vecuronium-associated axonal motor neuropathy: a variant of critical illness
      polyneuropathy?
AB  - Neuromuscular blocking agents are routinely used as an adjunct therapy for
      critically ill patients. Unlike many neuromuscular blocking agents, vecuronium
      does not cause significant histamine release, which may lead to
      bronchoconstriction. Due to a short duration of action and limited accumulation,
      vecuronium has been widely used. Prolonged ventilatory dependence due to
      persistent neuromuscular blockade has been reported in patients treated with
      vecuronium. We report a case of an 8-year-old girl who had a primarily motor
      axonopathy presenting with weakness after extended vecuronium administration with
      prolonged course of recovery. This primarily motor neuropathy with axonal
      features may be a variant of critical illness polyneuropathy, a rarely reported
      condition in pediatric patients.

PMID- 11525889
TI  - Ion channels in muscle and cardiac hereditary diseases: from gene dysfunction to
      pharmacological therapy. 10-11 March 2000, Bari, Italy.

PMID- 11525890
TI  - Report of the 83rd ENMC International Workshop: 4th Workshop on Nemaline
      Myopathy, 22-24 September 2000, Naarden, The Netherlands.

PMID- 11525892
TI  - President's page: Did you hear the one about the HIPAA-potamus and the
      investigator?

PMID- 11525893
TI  - Intermittent umbilical cord occlusion in the ovine fetus: effects on blood
      glucose, insulin, and glucagon and on pancreatic development.
AB  - OBJECTIVE: To determine whether repetitive umbilical cord occlusion resulting in
      fetal hypoxemia but not cumulative acidosis also affects fetal glucose levels and
      the levels of the regulatory hormones insulin and glucagon, by altering glucose
      delivery and with repetitive insults by inducing fetal glucose production, thus
      possibly affecting pancreatic development. METHODS: Fifteen chronically
      catheterized fetal sheep were studied over 21 days. Umbilical cord occlusions
      (UCOs) (duration 90 seconds) were performed every 30 minutes for 3-4 hours each
      day. Fetal arterial blood was sampled at predetermined times on days 1, 9, and 18
      for blood gases, pH, glucose, lactate, insulin, and glucagon. When animals were
      sacrificed, fetal pancreatic tissues were collected for insulin immunostaining.
      RESULTS: Blood glucose decreased acutely with each UCO but showed a cumulative
      increase of approximately 30% over the course of each sampling day. Although
      plasma insulin levels also increased over the course of sampling on days 9 and
      18, plasma glucagon levels remained unchanged throughout the study. The
      percentage of pancreatic islet cells immunopositive for insulin, which averaged
      67%, was also unchanged in experimental compared with control animals.
      CONCLUSION: Umbilical cord occlusion during the latter part of pregnancy, which
      caused severe but limited hypoxemia, also resulted in acute decreases in blood
      glucose levels because of reduced exogenous glucose delivery and a cumulative
      increase in glucose in response to repetitive insults, possibly by inducing fetal
      glucose production, enhancing glucose delivery, or both. However, repetitive UCO
      as studied had minimal effect on plasma insulin levels and no effect on glucagon
      levels or on pancreatic immunostaining for insulin, and thus had no evident
      effect on pancreatic development.

PMID- 11525894
TI  - Effects of mild hypothermia on metabolic disturbances in fetal hippocampal slices
      after oxygen/glucose deprivation depend on depth and time delay of cooling.
AB  - OBJECTIVE: There is increasing evidence from animal experiments that mild
      hypothermia induced during or after cerebral ischemia might protect the immature
      brain from neuronal cell damage. However, the exact interrelation between the
      postischemic time delay and the degree of mild hypothermia by which to achieve
      neuroprotective effects on ischemic insults of different severity has not yet
      been elucidated systematically. To determine optimal neuroprotection, we studied
      the interaction between these variables in a recently modified hippocampal slice
      model. METHODS: We investigated the recovery of energy metabolism and protein
      synthesis (PSR) in hippocampal slices from mature fetal guinea pigs after 20, 30,
      or 40 minutes of oxygen and glucose deprivation (OGD). Hypothermia of varying
      degrees was induced immediately or 2 or 4 hours after OGD and lasted for 12
      hours. Prolonged inhibition of PSR after ischemia has been shown to be a
      sensitive marker of neuronal cell damage. RESULTS: Hypothermia initiated
      immediately after OGD significantly improved the recovery of energy metabolism
      and PSR. If there was a 2-hour delay in the onset of hypothermia, neuroprotection
      depended on the degree of hypothermia. Reduction of the incubation temperature to
      31C diminished the disturbances of energy metabolism and PSR, whereas lowering
      the bath temperature to only 34C was not effective. Hypothermia induced 4 hours
      after OGD did not have any influence on the recovery of energy metabolism and
      PSR. CONCLUSION: We conclude that the effects of mild hypothermia on metabolic
      disturbances in hippocampal slices of mature fetal guinea pigs depended on the
      intervention delay and the degree of cooling. The shorter the postischemic
      intervention delay and the greater the degree of hypothermia, the better the
      neuroprotective effect seems to be.

PMID- 11525895
TI  - Chloride channel blockers 5-nitro-2-(3-phenylpropylamino) benzoic acid and
      anthracene-9-carboxylic acid inhibit contractions of pregnant rat myometrium in
      vitro.
AB  - OBJECTIVE: We compared in vitro relaxant effect of chloride channel modulators,
      such as 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB) and anthracene-9
      carboxylate (9-AC), and beta(2)-adrenergic agonists, such as ritodrine, in
      pregnant rat myometrium. METHODS: Isolated myometrial strips were obtained from
      eight pregnant rats, and the strips were mounted in organ baths for recording
      isometric tension. The effects of 10(-8)-10(-4) M ritodrine, 10(-6)-3 x 10(-4) M
      NPPB, and 10(-6)-10(-3) M 9-AC on spontaneous contractions were recorded.
      RESULTS: Ritodrine (10(-8)-10(-5) M) completely inhibited the amplitude and
      frequency of spontaneous contractions in myometrial strips isolated from pregnant
      rats in a concentration-dependent manner, but the relaxant effect of ritodrine at
      10(-4) M concentration resulted in tachyphylaxis. The chloride channel blocker
      NPPB (10(-6)-3 x 10(-4) M) and the chloride transport inhibitor 9-AC (10(-5)-10(
      3) M) decreased the amplitude of spontaneous myometrial contractions in a
      concentration-dependent manner; the maximum inhibition produced by the highest
      tested concentration of each drug was 43.8% and 42.1% of the original degree of
      spontaneous contractions, respectively. The frequency of myometrial contractions
      was significantly inhibited by NPPB and 9-AC beginning with the concentration of
      10(-4) M. CONCLUSION: NPPB and 9-AC appear to be effective relaxants of pregnant
      rat myometrium. These effects of NPPB and 9-AC might be therapeutically
      advantageous in clinical management of preterm labor.

PMID- 11525896
TI  - Nifedipine block of capacitative calcium entry in cultured human uterine smooth
      muscle cells.
AB  - OBJECTIVE: To determine whether nifedipine inhibits capacitative calcium entry at
      clinically relevant concentrations using cultured human myocytes as a model for
      human myometrium. METHODS: Myocyte cultures were initiated from the myometrium of
      term pregnant women who underwent cesarean delivery. Paired cells were chosen for
      study. The cell of interest was stimulated by an intercellular calcium wave from
      the adjacent cell. In this fashion, release of sarcoplasmic reticulum (SR)
      calcium was accomplished with minimal disturbance of the plasma membrane and the
      subplasmalemmal space (SPS) of the cell studied. Depletion of the SR calcium
      stores by the calcium wave activated the capacitative calcium current, elevated
      calcium in the SPS, and activated calcium-activated potassium channels. A cell
      attached patch clamp was used to monitor the outward current resulting from the
      calcium activation of these potassium channels. Calcium green-1 fluorescence was
      used to simultaneously monitor changes of the deep cytosolic calcium
      concentrations. Experiments were performed at varying concentrations of
      nifedipine (0-10 micromol/L). RESULTS: Nifedipine reduced outward potassium
      currents in a dose-dependent manner. Nifedipine at 100 nmol/L resulted in greater
      than a 50% reduction of outward current, indicating a significant inhibition of
      capacitative calcium entry at that concentration. Higher concentrations of
      nifedipine abolished outward current. Experiments designed to detect indirect
      effects of nifedipine on capacitative calcium entry were negative. CONCLUSIONS:
      Nifedipine block of capacitative calcium entry occurred at concentrations similar
      to those required to block L-type voltage-activated calcium channels. These data
      suggest that block of capacitative calcium entry may be an important mechanism of
      action when nifedipine is clinically used for tocolysis of preterm labor.

PMID- 11525897
TI  - Mouse ascites golgi (MAG) mucin expression and regulation by progesterone in the
      rat uterus.
AB  - OBJECTIVE: To study the regulation of the blood group A-related high-molecular
      weight mucin glycoprotein epitope (mouse ascites golgi, MAG)-a menstrual cycle
      dependent marker of endometrial receptivity-in a non-human endometrium model.
      METHODS: Immature Sprague-Dawley rats were injected with 1 microg of estradiol,
      100 microg of testosterone, 100 microg of dexamethasone, 2.5 mg of progesterone
      (P), 0.325 mg of RU486, P and RU486, 100 microg of tamoxifen, or vehicle for 3
      days, sacrificed, and the uteri were stained for MAG. Immunohistochemistry and
      blood analysis were the measurements used to compare the specimens from the
      exogenous hormonal and endogenous hormonal groups. Electron microscopy was used
      to locate the MAG epitope in one pseudopregnant adult Sprague-Dawley rat.
      RESULTS: The MAG epitope was present in endometrial glands of Sprague-Dawley
      rats, with maximal expression during proestrus and diestrus. Electron microscopy
      confirmed the Golgi location of this MAG epitope. In the untreated group, less
      than 0.5% of endometrial glands stained for MAG. The MAG was seen only in the
      glands of the P-treated rats and RU486 blunted this stimulatory effect by more
      than 95%. As little as 0.1 mg of P promoted MAG expression, with maximal response
      at 2.5 mg. Staining was seen 24 hours after P treatment, peaked at 72 hours, then
      declined. Induction of endogenous P by superovulation with pregnant mare serum
      gonadotropin (PMSG) and hCG (pseudopregnancy) also resulted in strong MAG
      glandular staining. CONCLUSION: Our results suggest that the MAG epitope is
      cyclically expressed and induced by P in rat endometrial glands.

PMID- 11525898
TI  - Antibody-induced anemia in fetal sheep: model for hemolytic disease of the fetus
      and newborn.
AB  - OBJECTIVE: Our purpose was to produce a condition analogous to alloimmune
      hemolytic disease of the fetus and newborn by infusing antierythrocyte antibodies
      in fetal sheep. METHODS: Antierythrocyte antibodies were infused intravascularly
      into late-gestation ovine fetuses over a 10-day period. Fetal blood was sampled
      daily for complete blood cell counts, blood gases, iron, erythropoietin (EPO),
      and electrolyte concentrations. Red cell mass (RCM) and blood volume were
      determined every other day using indicator dilution techniques. Results were
      compared with eight similarly aged control animals. Statistical analysis included
      Student t test, three-factor analysis of variance, and least squares regression.
      RESULTS: The hematocrit in seven fetal sheep receiving antibody infusion declined
      significantly by 10.3 +/- 1.7%, whereas it increased in control animals 2.3 +/-
      0.6% (P <.001). RCM was reduced by 18.9 +/- 3.2% over the 10-day protocol while
      increasing 34.1 +/- 4.2% in control animals, representing more than a 50%
      difference in RCM (P <.001). Fetal EPO was significantly increased with lower
      hematocrit and lower PO(2) (P <.001). As fetal hematocrit declined below 25%,
      lactate and reticulocytes also increased (P <.001). Plasma iron concentration was
      not significantly altered (P =.47). CONCLUSIONS: The chronically catheterized
      fetal sheep is a viable model for studying immunologically induced fetal anemia
      as hematocrit can be titrated and the fall in RCM and hematocrit are associated
      with fetal hypoxia and elevated EPO as occurs in the anemic human fetus.
      Furthermore, there appears to be a threshold degree of anemia required to elicit
      responses as the fetal EPO, PO(2), and lactate appeared unresponsive until
      hematocrit fell below 25%.

PMID- 11525899
TI  - Salmon GnRH and its analogues bind the human placental receptor.
AB  - OBJECTIVE: The presence of GnRH receptors in the human placenta has been
      recognized for a number of years. However, mammalian GnRH, which is expressed in
      placental tissues, has limited affinity for the chorionic receptor. On the basis
      of immunological and bioactivity data, we have previously proposed that the
      chorionic GnRH may differ from mammalian GnRH. METHODS: We have studied the
      affinity of another isoform of GnRH (ie, salmon GnRH and stable analogues of this
      GnRH isoform), and compared their receptor affinity to that of mammalian GnRH and
      its analogues. RESULTS: Using our receptor assay method with the labeled
      mammalian GnRH analogue Buserelin, salmon GnRH had a twofold greater affinity for
      the placental GnRH receptor than did mammalian GnRH and for the stable salmon
      GnRH analogue the affinity was increased tenfold. Using a homologous receptor
      assay method with a stable salmon GnRH analogue as label, the affinity for this
      salmon GnRH analogue had a K(d) of 101 nmol/L. CONCLUSION: The presence of these
      higher affinity receptors for non-mammalian GnRH in the human placenta has led us
      to propose that the chorionic tissues may express more than one isoform of GnRH
      and that non-mammalian GnRH, such as salmon GnRH, may be potent regulators of
      placental functions.

PMID- 11525900
TI  - Influence of ET(B) receptor antagonism on pregnancy outcome in rats.
AB  - OBJECTIVE: To determine the effect of endothelin-B (ET(B))-selective receptor
      antagonism on pregnancy outcome in normal rats. METHODS: ET(B) receptor
      antagonist (A-192621; 5.0, 10.0, and 15.0 mg/kg per day) or vehicle was infused
      subcutaneously for 7 days by osmotic pump. Infusion was begun on day 14 of a 22
      day gestation. Nonpregnant animals were treated similarly, and blood pressure
      (BP) responses and plasma antagonist levels were compared to those in pregnant
      animals. Mean arterial pressure (MAP) was measured on days 1, 4, and 7 of the
      infusion. Plasma ET(B) antagonist levels were measured on day 7 of infusion. On
      gestational day 21, fetal and placental weights and viability were evaluated at
      hysterotomy. Data were analyzed by analysis of variance and are presented as mean
      +/- standard error of the mean. RESULTS: Fetal and placental weights were
      significantly lower at doses of 10 and 15 mg/kg per day of the ET(B) antagonist
      compared with vehicle-treated controls (P <.001); these effects were less severe
      at 15 than at 10 mg/kg per day despite a fourfold higher plasma level of
      antagonist. Mean arterial pressure was significantly higher at 10 and 15 mg/kg
      per day compared with controls, but only on infusion day 1 (P <.05). In contrast,
      MAPs for nonpregnant rats were elevated throughout the infusion at all doses of
      the ET(B) antagonist (P <.05). CONCLUSIONS: ET(B) receptor antagonism inhibited
      fetal growth and increased maternal MAP in a dose-dependent manner, although the
      effect on BP was not sustained in pregnant animals. ET(B) receptor antagonism is
      detrimental to pregnancy outcome in the rat.

PMID- 11525901
TI  - Differential neuroprotective effects of equine estrogens against oxidized low
      density lipoprotein-induced neuronal cell death.
AB  - OBJECTIVE: In the present study, the neurotoxic effect of oxidized low density
      lipoprotein on PC-12 neuronal cells maintained in culture was used to test the
      neuroprotective effect of several equine estrogens, such as estrone (E(1)),
      17beta-estradiol (17beta-E(2)), 17alpha-estradiol (17alpha-E(2)), equilin (Eq),
      17beta-dihydroequilin (17beta-Eq), 17alpha-dihydroequilin (17alpha-Eq), equilenin
      (Eqn), 17beta-dihydroequilenin (17beta-Eqn), 17alpha-dihydroequilenin (17alpha
      Eqn), Delta(8)-estrone (Delta(8)-E(1)), and Delta(8),17beta-estradiol
      (Delta(8),17beta-E(2)). METHODS: The PC-12 cells (10,000 cells/well) were grown
      on collagen-coated 96-well plates in Dulbecco's Modified Eagle Medium
      supplemented with 10% horse serum, 5% fetal bovine serum, and 10 mM HEPES. In
      culture, the cells displayed normal PC-12 morphology and behavior, exhibiting
      increased dendritic growth and cessation of cell division upon exposure to nerve
      growth factor. Twenty-four hours after plating, various concentrations (0.1-50
      microM) of estrogens were added followed by addition of oxidized low density
      lipoprotein (5-12.5 microg/well) in a total volume of 100 microL. After 24 hours,
      cell viability was determined using the MTS (3-[4,5-dimethylthiazol-2-yl]-5-[3
      carboxymethoxyphenyl]-2H-tetrazolium, inner salt) cell proliferation assay.
      RESULTS: The results indicate that the extent of low density lipoprotein
      oxidation and concentration of oxidized low density lipoprotein is directly
      proportional to cell toxicity. The mean +/- standard deviation cell death
      obtained using 10.0 microg/well of oxidized low density lipoprotein was 53.6% +/-
      8.7%. With the exception of 17alpha-estradiol, all estrogens tested were found to
      be neuroprotective against oxidized low density lipoprotein toxicity in a typical
      dose-dependent manner. The order of neuroprotective potency was Delta(8)-E(1)
      (1.2 microM), Delta(8),17beta-E(2) (1.3 microM), Eqn (5.3 microM), 17beta-Eqn
      (5.3 microM), Eq (6 microM), 17beta-Eq (8.5 microM), E(1) (11 microM), 17beta
      E(2) (11 microM), 17alpha-Eq (12 microM), and 17alpha-Eqn (16 microM) followed by
      17alpha-E(2) which provided less than 50% protection. CONCLUSION: Our data
      indicate that the neurotoxic effects of oxidized low density lipoprotein can be
      inhibited differentially by various estrogens, with the Delta(8) estrogens being
      the most potent neuroprotectors. These novel findings further suggest that some
      of the neuroprotective benefits associated with estrogen therapy might occur by
      the suppression of oxidized low density lipoprotein neurotoxicity. Because
      estrogens such as Delta(8)-E(1) are relatively less uterotropic and potentially
      less feminizing than the classic estrogen 17beta-E(2), they may be useful in the
      prevention of Alzheimer disease and other neurodegenerative diseases in both
      women and men.

PMID- 11525902
TI  - Anomalous mutagenicity profile of cyclohexanone oxime in bacteria: cell survival
      in background lawns.
AB  - The basis for the observed mutagenicity of cyclohexanone oxime in the presence of
      hamster liver S9 in Salmonella typhimurium strain TA1535, but not in TA100, was
      explored. While the chemical had no effect on the appearance of the background
      lawn in either strain, it did cause a reduction in mutant colony counts in strain
      TA100, raising the possibility of selective toxicity to this strain. Viability of
      the two strains was determined directly by titering the cells in background lawns
      over a 3 day period. In order to do this, cells embedded in top agar overlays
      were released by extruding agar plugs through small holes in the bottoms of
      centrifuge tubes, followed by vigorous vortexing. Viable cell counts in
      background lawns of strain TA100, but not strain TA1535, were greatly reduced in
      the presence of cyclohexanone oxime. Most of the loss of viable TA100 cells
      occurred on days 2 and 3 following plating, after the cells had exhausted the
      histidine in the medium and stopped growing. Therefore, the observed loss of
      background lawn viable cells is unlikely to be the cause of the non-mutagenicity
      of cyclohexanone in strain TA100. Analysis of reversion spectra showed that
      cyclohexanone oxime-induced C-->T transitions in the second position of the CCC
      triplet at the his mutation site in strain TA1535, but had no significant effect
      on any transition or transversion in strain TA100.

PMID- 11525903
TI  - Differential activation of mitogen-activated protein kinases by methyl
      methanesulfonate in the kidney of young and old rats.
AB  - Mitogen-activated protein kinases (MAPKs) play a critical role in the regulation
      of cell proliferation, differentiation and apoptosis. We evaluated MAPKs,
      extracellular signal-regulated kinases (ERKs), c-Jun NH2-terminal kinases (JNKs)
      and p38 MAPKs in the kidney of young and old rats in response to a direct-acting
      alkylating agent, methyl methanesulfonate (MMS). It is shown that the basal
      activity of ERKs was strongly down-regulated in the kidney of old rats compared
      to their young counterparts without a significant difference in the basal
      expression of ERKs. Upon treatment with MMS, ERKs were deactivated about 5-fold
      (P<0.05) in the kidney of young rats, whereas they were activated about 4-fold
      (P<0.01) in old rats. Strikingly, expression of JNKs was not detected in old
      animals, whereas it was clearly present and strongly activated after MMS
      treatment in the kidney of young animals. The basal activity of p38 significantly
      increased in the kidney of old rats as compared to young animals, whereas no
      difference in the basal expression of p38 was detected. After treatment with MMS,
      p38 was activated in the kidney of both young and old rats, where activation was
      dramatically stronger than in young animals. Taken together, these results
      demonstrate age-specific MAPKs signaling pathways in the rat kidney. The
      implications in age-related changes in susceptibility of the kidney to MMS
      induced carcinogenesis are discussed.

PMID- 11525904
TI  - Genotoxic effects of copper sulphate in freshwater planarian in vivo, studied
      with the single-cell gel test (comet assay).
AB  - The alkaline single-cell gel electrophoresis, or comet assay, was used to
      evaluate the genotoxic potential of copper sulphate in planarians. Concentration
      related increase in DNA damage was induced after 2h and 7 days exposure to CuSO4
      dissolved in culture water. To study the influence of copper ions on the
      persistence of mutagen-induced DNA lesions, planarians were treated with methyl
      methanesulphonate (MMS), and further incubated in the absence (post-incubation)
      or presence (post-treatment) of CuSO4. After 2h of post-treatment enhanced
      persistence of DNA effects in relation to the corresponding post-incubation value
      was detected, which indicate inhibition of DNA repair by CuSO4. At 4h an increase
      of DNA migration in relation to the 2h value was observed, which is significant
      for the post-incubation group. After 24h, DNA damage decreased but was still
      significantly elevated in relation to the control. From our results, we conclude
      that planarians are suitable organisms for in vivo detection of copper
      genotoxicity in the comet assay, and can be used to assess both acute and chronic
      exposure to this chemical in aquatic ecosystems. The inhibition effect of copper
      ions on repair of MMS-induced DNA damage suggests that copper could modulate the
      genotoxic effects associated with complex mixture exposure in the environment.

PMID- 11525905
TI  - Differentiation of the mechanism of micronuclei induced by cysteine and
      glutathione conjugates of methylenedi-p-phenyl diisocyanate from that of 4,4'
      methylenedianiline.
AB  - Methylenedi-p-phenyl diisocyanate (MDI) is widely used in the production of
      polyurethane products. Diisocyanates are reactive compounds, MDI can react under
      physiological conditions with various functional groups found on biological
      molecules resulting in conjugate formation or undergo non-enzymatic hydrolysis to
      form 4,4'-methylenedianiline (MDA). We have previously reported that addition of
      MDI directly to Chinese hamster lung fibroblasts (V79) cultures did not induce
      micronuclei (MN), but MDA, and the glutathione and cysteine conjugates of MDI
      (BisGS-MDI and BisCYS-MDI), induced a concentration-dependent increase in the
      frequency of MN. The conventional MN assay does not discriminate between MN
      produced by acentric chromosome fragments from those arising due to whole lagging
      chromosomes that were not incorporated into daughter nuclei at the time of cell
      division. The mechanism of MN induction from these potential MDI
      metabolites/reaction products was explored in the present study using
      immunofluorescent staining of kinetochore in MN of cytokinesis-blocked V79 cells.
      This assay discerns the presence of centromere within the MN to distinguish the
      MN containing centric chromosomes from those containing acentric fragments.
      Eighty five percent of MDA-induced MN were negative with respect to anti
      kinetochore antibody binding (KC(-)). This is consistent with an interaction
      between MDA and DNA resulting in chromosome breakage. However, BisGS-MDI and
      BisCYS-MDI induced a higher percentage of MN that were positively stained by the
      anti-kinetochore antibody (KC(+)). These results suggest that the mechanism of MN
      formation induced by BisGS-MDI and BisCYS-MDI is mediated through disruption
      and/or by affecting the function of the mitotic spindle. This mechanism is
      distinctly different from the mechanism of MN induction by MDA.

PMID- 11525906
TI  - Epithelial and fibroblast cell lines cultured from the transgenic BigBlue rat: an
      in vitro mutagenesis assay.
AB  - We have isolated, cultured, and immortalised three new BigBlue transgenic rat
      cell lines for the study of mutation induction in vitro. The two epithelial cell
      lines, from the mammary gland and oral cavity, were designated BBR/ME and BBR/OE,
      respectively, and the third is a mammary fibroblast line designated BBR/MFib. We
      have characterised these cell lines with respect to chromosome number and the
      expression of some cell-specific antigens. The clonogenic survival and cII
      transgene mutation induction responses of these three cell lines to N-ethyl-N
      nitrosourea (ENU) treatment were determined. Both epithelial cell lines were much
      more sensitive to ENU toxicity than was the fibroblast cell line. However, all
      cell lines showed similar ENU dose-dependent increases in mutant frequency. We
      hope that cell lines such as these will extend the power of the BigBlue assay to
      in vitro studies.

PMID- 11525907
TI  - Aryl hydrocarbon receptor-mediated activity of mutagenic polycyclic aromatic
      hydrocarbons determined using in vitro reporter gene assay.
AB  - Activation of aryl hydrocarbon receptor (AhR) by 30 polycyclic aromatic
      hydrocarbons (PAHs) was determined in the chemical-activated luciferase
      expression (CALUX) assay, using two exposure times (6 and 24h), in order to
      reflect the metabolization of PAHs. AhR-inducing potencies of PAHs were expressed
      as induction equivalency factors (IEFs) relative to benzo[a]pyrene and 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD). In 24h exposure assay, the highest IEFs were
      found for benzo[k]fluoranthene, dibenzo[a,h]anthracene and
      dibenzo[a,k]fluoranthene (approximately three orders of magnitude lower than
      TCDD) followed by dibenzo[a,j]anthracene, benzo[j]fluoranthene, indeno[1,2,3
      cd]pyrene, and naphtho[2,3-a]pyrene. The 6h exposure to PAHs led to a
      significantly higher AhR-mediated activity than the 24h exposure (generally by
      two orders of magnitude), probably due to the high rate of PAH metabolism. The
      strongest AhR inducers showed IEFs approaching that of TCDD. Several PAHs,
      including some strong mutagens, such as dibenzo[a,l]pyrene, cyclopenta[cd]pyrene,
      and benzo[a]perylene, elicited only partial agonist activity. Calculation of IEFs
      based on EC25 values and/or 6h exposure data is suggested as an alternative
      approach to estimation of toxic potencies of PAHs with high metabolic rates
      and/or the weak AhR agonists. The IEFs, together with the recently reported
      relative mutagenic potencies of PAHs [Mutat. Res. 371 (1996) 123; Mutat. Res. 446
      (1999) 1] were combined with data on concentrations of PAHs in extracts of model
      environmental samples (river sediments) to calculate AhR-mediated induction
      equivalents and mutagenic equivalents. The highest AhR-mediated induction
      equivalents were found for benzo[k]fluoranthene and benzo[j]fluoranthene,
      followed by indeno[1,2,3-cd]pyrene, dibenzo[a,h]anthracene, benzo[a]pyrene,
      dibenzo[a,j]anthracene, chrysene, and benzo[b]fluoranthene. High mutagenic
      equivalents in the river sediments were found for benzo[a]pyrene,
      dibenzo[a,e]pyrene, and naphtho[2,3-a]pyrene and to a lesser extent also for
      benzo[a]anthracene, benzo[b]fluoranthene, indeno[1,2,3-cd]pyrene,
      benzo[j]fluoranthene, dibenzo[a,e]fluoranthene and dibenzo[a,i]pyrene. These data
      illustrate that AhR-mediated activity of PAHs, including the highly mutagenic
      compounds, occurring in the environment but not routinely monitored, could
      significantly contribute to their adverse effects.

PMID- 11525908
TI  - Chromosomal aberrations, sister chromatid exchanges and micronuclei induced by
      pentoxifylline in in vitro cultivated Chinese hamster cells (V79) and human blood
      lymphocytes.
AB  - Pentoxifylline (PTX) is a methylxanthine widely used in clinical practice. The
      mechanism of PTX effects on cellular and molecular level have not been fully
      explained yet. The present study was carried out to investigate the cytogenetic
      effect of this drug using cultured Chinese hamster V79 cells and human blood
      lymphocytes in vitro. The occurrence of chromosomal aberrations (CA), sister
      chromatid exchanges (SCE) and micronuclei (MN) was observed after the treatment
      of cells by different concentrations (0.002-2.0mg/ml) of PTX. In exposed V79
      cells and lymphocytes as well, the dose-dependent increases of the above
      mentioned cytogenetic endpoints were found. The statistically significant
      increase has appeared at lower PTX concentrations in human lymphocytes than in
      V79 cells in all the investigated parameters. Our results show that, the applied
      concentrations of PTX has the clastogenic effect on in vitro cultured V79 cells
      and human lymphocytes. These findings are notable because of the frequent use of
      this drug and may serve as preliminary data to the further detailed examination
      of PTX action on molecular level.

PMID- 11525909
TI  - Testing the SCE mechanism with non-poisoning topoisomerase II inhibitors.
AB  - There are controversial theoretical models about a possible involvement of DNA
      topoisomerase II (topo II) in the molecular mechanism of sister chromatid
      exchanges (SCEs). In order to clarify the role of this enzyme, if any, in such
      recombinational event, CHO parental AA8 and mutant EM9 cells, which shows and
      extremely high baseline frequency of SCE, have been treated with different doses
      of the non-poisoning topoisomerase inhibitors, ICRF-193 and bufalin. The
      frequencies of SCEs after the treatments have been determined and the inhibitory
      effect of these compounds has been assessed using a topo II activity assay. The
      results indicate that ICRF-193 and bufalin effectively inhibit topo II activity
      in AA8 and EM9 cell lines. ICRF-193 induced a moderate increase in the frequency
      of SCEs in both types of cells, while bufalin did not modify the level of SCEs in
      any of them. The results are discussed taking into account the apparently unlike
      mechanisms of inhibition of topo II by ICRF-193 and bufalin.

PMID- 11525910
TI  - Genotoxic effects of radiotherapy and chemotherapy on circulating lymphocytes in
      patients with Hodgkin's disease.
AB  - PURPOSE: The aim of this study was to find out the structural chromosomal changes
      in somatic cells after chemotherapy (CT) with or without radiotherapy (RT).
      METHODS AND MATERIALS: This prospective study included 30 Hodgkin's disease (HD)
      patients. The patients of Group I(1) had only MOPP/ABV CT. The patients of Group
      II(2) also had irradiation. Group III(3) (control group) consisted of healthy
      subjects without any reported malignant disease. Mutagenetic testing was
      performed at the time of diagnosis and was repeated immediately after treatment
      and again 6 months later. The following tests were applied: structural
      chromosomal aberrations (CA), sister chromatid exchange (SCE) and micronucleus
      (MN) tests. RESULTS: Prior to treatment, the chromosome damage in our patients
      was not higher than that in the control group. Immediately after the complete
      treatment, we observed a strong inhibition of the mitotic activity of lymphocytes
      as well as a significant increase in the frequency of CA, MN and SCE in the
      Groups I and II. In patients treated by RT, we found statistically significant
      differences between the Groups I and II in MN (P<0.005) and CA frequencies
      (P<0.005), and an increased number of dicentrics (P=0.021). Six months after the
      complete treatment, the mitotic activity was found to be nearly normal, but
      chromosome damage occurred. CA and SCE values did not differ much from the values
      measured immediately after treatment, whereas MN values decreased without
      returning to the baseline levels. The chromosome damage persisted even 6 months
      after combined RT and CT. The damage in the genome of individual cells was in
      some cases even greater than immediately after treatment. The possible risk of
      neoplastic transformation posed by these heavily damaged cells, if viable, due to
      the changes in the expression of oncogenes or tumour suppresser genes, is
      discussed.

PMID- 11525911
TI  - Mutagenic and cytotoxic effectiveness of zinc dimethyl and zinc
      diisononyldithiocarbamate in human lymphocyte cultures.
AB  - The mutagenic and cytotoxic effectiveness of the vulcanisation accelerators zinc
      dimethyldithiocarbamate (ZDMC; ziram) and zinc diisononyldithiocarbamate (ZDINDC;
      arbestab Z) was tested in lymphocyte cultures of five healthy probands. ZDMC and
      ZDINDC (c=0.1, 1.0 and 10.0microg/ml) were studied in lymphocyte cultures without
      external metabolic activation. Additionally, incubation of the compounds
      (c=10.0microg/ml) was performed in the presence of liver microsomes from aroclor
      induced rats (1 and 2h, 1 and 2mg microsomal protein). Genotoxicity testing was
      performed by analysis of chromosomal aberrations (CA), sister chromatid exchanges
      (SCEs) and micronuclei (MN). For evaluation of antiproliferative effects, mitotic
      index (MI) and cell cycle kinetics (CCK) were determined. In contrast to earlier
      investigations we found no significantly increased mutagenic or cytotoxic
      activity of ZDMC; ZDINDC also was inactive under these conditions.

PMID- 11525912
TI  - The genotoxic risk of hospital, pharmacy and medical personnel occupationally
      exposed to cytostatic drugs--evaluation by the micronucleus assay.
AB  - The aim of this study was to evaluate the genotoxicity of cytostatic drugs in
      hospital and pharmacy employees (n=100), occupationally exposed. The micronucleus
      assay was used to study lymphocytes in 247 peripheral blood samples. Samples were
      collected at "baseline level" without any cytostatic drugs exposure before
      recruiting or after at least 3 weeks without cytostatic drugs contact and at
      three times (cycle 1-3) post-exposure. Samples from 60 office employees served as
      controls. Furthermore, our results were compared to urinary analyses of
      cytostatic drugs (oxazaphosporines, anthracyclines, platinum) which were
      collected in parallel to the cytogenetic investigation. Statistical analyses were
      performed under consideration of age, gender and X-ray exposure. The frequency of
      micronuclei was significantly related to the age of the subjects
      (r(Spearman)=0.16; P<0.05). However, there were no significant differences in
      micronucleus rates between controls and exposed hospital workers. Similarly,
      micronucleus rates were not significantly different at the various sampling time
      points and there was no correlation between duration of employment and
      micronucleus rates. Furthermore, no correlation between current biomonitoring
      data of exposure (urine tests) and micronuclei frequency was found. Therefore,
      significantly increased genotoxic damage of the lymphocytes investigated in this
      study could not be demonstrated.

PMID- 11525913
TI  - The effectiveness of the O(6)-alkylguanine-DNA alkyltransferase encoded by the
      ogt(ST) gene from S. typhimurium in protection against alkylating drugs,
      resistance to O(6)-benzylguanine and sensitisation to dibromoalkane genotoxicity.
AB  - Here we demonstrate that the Ogt(ST) from Salmonella typhimurium is a highly
      efficient O(6)-alkylguanine-DNA alkyltransferase (AGT) in affording protection
      against antitumour chloroethylating drugs (1,3-bis(2-chloroethyl)-1-nitrosourea
      (BCNU) and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU)). In addition,
      Ogt(ST) is refractory to O(6)-benzylguanine (BG) inactivation and its expression
      provides only minor sensitisation to genotoxicity by environmental dibromoalkanes
      (DBE). No other of the assayed bacterial or human AGTs displayed such
      advantageous properties for chemoprotective gene therapy strategy. Our
      observations indicate that the Ogt(ST) AGT might be, under some circumstances, of
      potential use to improve cancer chemotherapy. At least, its properties may
      provide further insight into the design of human AGT variants that could be
      expressed in normal or tumour cells to provide either protection or ablation.

PMID- 11525914
TI  - Desmutagenic and bio-antimutagenic activity of docosahexaenoic acid and
      eicosapentaenoic acid in cultured Chinese hamster V79 cells.
AB  - The antimutagenic activities of docosahexaenoic acid (DHA) and eicosapentaenoic
      acid (EPA) were examined by studying their effects on induction of 6-thioguanine
      (6TG)-resistant mutations by ethyl methanesulfonate (EMS) in cultured Chinese
      hamster V79 cells. DRA had a remarkable inhibitory effect against the
      cytotoxicity of EMS, when cells were simultaneously-treated with EMS, showing a
      blocking or scavenging activity of DHA in reduction of surviving fraction of
      cells. DHA had not so significant effect, when cells were treated before and
      after treatment with EMS. On the other hand, EPA had marked inhibiting effects
      against cytotoxicity of EMS, when cells were treated with EPA, before,
      simultaneous and after treatment with EMS. Against the induction of mutations by
      EMS, an antimutagenic activity of DHA was found when cells were pre-treated,
      simultaneously-treated or post-treated with DHA. EPA was also effective in
      reducing EMS-induced 6TG-resistant mutations when the cells were treated using
      the three different treatment procedures described above. The results suggest
      that in cultured Chinese hamster V79 cells, DHA and EPA may have both
      desmutagenic activity, which inactivates EMS chemically and/or enzymatically and
      bio-antimutagenic activity which suppresses mutation fixation after DNA is
      damaged by EMS.

PMID- 11525915
TI  - An in vivo evaluation of induction of abnormal sperm morphology by some
      anthelmintic drugs in mice.
AB  - Using the murine sperm-head abnormality test, the mutagenicity of pyrantel
      pamoate, levamisole, albendazole, mebendazole and niridazole was evaluated.
      Pyrantel pamoate and niridazole induced increases in sperm-head abnormalities
      statistically significant over the negative controls at all the dose levels that
      were considered; the induction was dose-dependent indicating that both drugs
      might be mutagenic. Levamisole, albendazole, mebendazole and thiabendazole, all
      were unable to induce statistically significant increases in sperm-head
      abnormalities over the negative controls at all the dose levels tested; there was
      no correlation between dose level of administered drugs and incidence of abnormal
      sperms, indicating that the drugs might not be mutagenic.

PMID- 11525916
TI  - Investigation of genotoxic and antigenotoxic activities of chlorophylls and
      chlorophyllin in cultured V79 cells.
AB  - Chlorophyll and its derivatives are examples of plant compounds (purified and/or
      extracted) which appear to protect DNA from damage caused by chemical or physical
      agents, although some studies have identified clastogenic activity of these
      compounds. This study was carried out to assess the genotoxic activity of
      chlorophyll-a (Chl-a), -b (Chl-b) and chlorophyllin (Chl) and their antigenotoxic
      activity against the DNA damage induced by methyl methanesulphonate (MMS) under
      conditions of simultaneous, pre-, post-treatment, and simultaneous treatment
      after pre-incubation of the chemical with MMS. The micronucleus (MN) test was
      used in binucleated cells (induced by cytochalasin-B) of a mammalian cell line
      (V79). The three concentrations of Chl-a, Chl-b or Chl (0.1375, 0.275,
      0.55microM) were not genotoxic and the genotoxic action of MMS (400microM)
      decreased (74-117%) under all treatment conditions. The results showed that there
      was no significant difference among the treatment types, the concentration or the
      nature of chlorophyll used. The data obtained suggest that Chl-a, Chl-b and Chl
      when associated with the DNA damaging agent, MMS, may protect the DNA by
      desgenotoxic action and/or by bio-antigenotoxic mechanisms, with the similar
      efficiency.

PMID- 11525917
TI  - Induction of micronuclei in mouse polychromatic erythrocytes by the
      administration of non-radioactive CsCl by the oral and intraperitoneal route.
AB  - In the present study, we describe the effects of the concentration and route of
      administration of non-radioactive cesium chloride (CsCl) in inducing micronuclei
      in mouse bone marrow polychromatic erythrocytes (PCEs). When the dose of 500mg/kg
      body weight was administered perorally (p.o.), no significant incidence of
      micronuclei was detected. However, when the same dose was administered
      intraperitoneally (i.p.), a significant induction of micronuclei in PCEs was
      observed compared to control. At the dose of 1000mg/kg, both routes were
      efficient, with no significant difference in micronucleus frequencies. We
      conclude that both the p.o. and i.p. routes are efficient in inducing
      micronuclei, with the i.p. route being more efficient when lower CsCl doses are
      used.

PMID- 11525918
TI  - Mutagenicity of the malondialdehyde oligomerization products 2-(3'-oxo-1'
      propenyl)-malondialdehyde and 2,4-dihydroxymethylene-3-(2,2
      dimethoxyethyl)glutaraldehyde in Salmonella.
AB  - Malondialdehyde (MDA), a byproduct of non-enzymatic lipid peroxidation and
      prostaglandin biosynthesis, has been shown to be a weak frameshift mutagen in
      Salmonella mutagenicity assays. Because it is a dialdehyde, MDA can undergo self
      condensation to form polymeric products. It is possible that these condensation
      products are highly mutagenic and have contributed to previously reported
      estimates of MDA mutagenicity. We synthesized two major MDA polymerization
      products, (1) 2-(3'-oxo-1'-propenyl)-malondialdehyde [(MDA)2] and (2) 2,4
      dihydroxymethylene-3-(2,2-dimethoxyethyl)glutaraldehyde [(MDA)3Me2] and tested
      their mutagenicity in the Salmonella frameshift tester strains hisD3052 and TA94
      (hisD3052/pKM101). Analysis of the reversion rates revealed both (MDA)2 and
      (MDA)3Me2 to be weak mutagens, approximately equipotent to MDA. Although both
      (MDA)2 and (MDA)3Me2 are mutagenic, the fact that their formation is
      thermodynamically unfavorable under physiological conditions suggests they do not
      contribute significantly to the mutagenicity of MDA solutions.

PMID- 11525919
TI  - Mutagenicity of nitric oxide-releasing compounds in Escherichia coli: effect of
      superoxide generation and evidence for two mutagenic mechanisms.
AB  - The mutagenicity of three nitric oxide (NO) donors, 3-morpholinosydnonimine (SIN
      1), a compound generating the precursors of peroxynitrite NO and superoxide,
      diethylamine/NO (DEA/NO) and spermine/NO (SPER/NO), both releasing authentic NO
      was analyzed using Escherichia coli tester strains IC203, carrying a deletion of
      the oxyR gene, and its oxyR(+) parent IC188 (the alternative name of WP2
      uvrA/pKM101). The OxyR protein is a redox-sensitive transcriptional activator of
      genes encoding antioxidant enzymes. Strains IC203 and IC188 contain error-prone
      DNA polymerases polV, encoded by the chromosomal umuDC genes, and polRI, encoded
      by mucAB genes carried by pKM101. SIN-1 was determined to be an oxidative mutagen
      giving a positive response only in IC203, whereas DEA/NO and SPER/NO induced
      similar positive responses in IC203 and IC188 and were considered as non
      oxidative mutagens. The spectrum of ochre suppressors in Trp(+) revertants
      induced by SIN-1 in IC203 was characterized by a higher number of TA-->AT
      transversions and GC-->AT transitions, and a lower number of GC-->TA
      transversions, with respect to the untreated control. The mutagenicity of SIN-1
      in IC203, probably induced by peroxynitrite through reactive derivatives, was
      enhanced in the presence of plumbagin (PLB), a superoxide generator. Superoxide
      generation by PLB, as well as formation of peroxynitrite in cells treated with
      SIN-1, evaluated by monitoring the oxidation, respectively, of dihydroethidium
      and dihydrorhodamine 123, were greater in IC203 than in IC188. Formation of
      peroxynitrite in IC203 treated with SIN-1 was stimulated by PLB. After treatment
      with DEA/NO and SPER/NO the number of revertants scored in IC188 was higher than
      in strains IC187, containing only polV, and IC204, deficient in both polV and
      polRI. For these compounds, induced suppressor revertants in IC187 and IC204 were
      almost exclusively GC-->AT transitions, whereas in IC188 significant levels of GC
      ->TA and TA-->AT transversions were also induced. Mutagenesis by both DEA/NO and
      SPER/NO was partially inhibited in the presence of PLB. The results show the
      usefulness of the new tester strain IC203 to differentiate NO-promoted mutagenic
      mechanisms that involve or do not involve oxygen radicals.

PMID- 11525920
TI  - Contribution of apoptosis to responses in the comet assay.
AB  - Apoptosis, a physiological process of selected cell deletion, leads to DNA
      fragmentation in typical segments of 180 base pairs. DNA strand breaks are also
      an effect induced by genotoxic compounds. The aim of this study was to compare
      these two types of damaging potentials by a known genotoxic substance and an
      apoptosis-inducing agent in HT-29 colon adenocarcinoma cells. The cells were
      incubated for 24h with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), a potent DNA
      damage-inducing agent, staurosporine, an inhibitor of protein kinase C and
      apoptosis-inducing agent, and hydrogen peroxide, a source of reactive oxygen
      species. Apoptosis was measured with the Annexin V affinity assay which detects
      the translocation of phosphatidylserine (PS) from the inner to the outer leaflet
      of the cytoplasmic membrane, an early event in the apoptotic process. DNA damage
      as an end point of genotoxicity was detected by single cell microgel
      electrophoresis, also called "comet assay". The results show that apoptosis does
      not necessarily need to correlate or coincide with DNA damage observed with
      genotoxic substances in the comet assay. The representative apoptosis-inducing
      agent (staurosporine) did not induce strand breaks in the tested concentrations
      (0.5 and 1.0microM); genotoxic doses of the strand break inducing agent MNNG did
      not induce apoptosis. Therefore, the comet assay can be used as a specific test
      for detecting genotoxicity, and the results are not necessarily confounded by
      concomittant processes leading to apoptosis.

PMID- 11525921
TI  - Genotoxic evaluation of the furylethylene derivative 2-furyl-1-nitroethene in
      cultured human lymphocytes.
AB  - The compound 2-furyl-1-nitroethene (G-0) was evaluated for genotoxicity in
      cultured human peripheral blood lymphocytes, at concentrations ranging from 1 to
      15microg/ml. Micronuclei (MN) and sister-chromatid exchanges (SCEs) were scored
      as genetic endpoints. In order to detect the role of metabolic enzymes on the
      genotoxicity of this furylethylenic derivative, the cultures for MN and SCE
      demonstrations were also treated with S9 microsomal fraction. The results
      indicate that, under the conditions of the study, the test agent does not seem to
      induce significant increases in the frequency of micronucleated cells,
      irrespective of the presence of metabolic activation. Nevertheless, a slight
      increase in the SCE frequency was observed in those cultures treated without the
      S9 mix; although this increase disappeared in presence of the microsomal
      fraction. In addition, cytostatic effects of 2-furyl-1-nitroethene were observed
      mainly in cultures without S9 fraction, as indicated by the reduction of cell
      proliferation.

PMID- 11525922
TI  - DNA-damaging potential and glutathione depletion of 2-cyclohexene-1-one in
      mammalian cells, compared to food relevant 2-alkenals.
AB  - 2-Cyclohexene-1-one (CHX) occurs as a natural ingredient in some tropical fruits
      and has been detected as a contaminant in certain artificially sweetened soft
      drinks. To elucidate its cytotoxic/genotoxic effectiveness, CHX was tested in
      mammalian cell lines (V79 and Caco-2) and in primary human colon cells in
      comparison to structurally related 2-alkenals. Inhibition of cell growth (IC(50))
      and cytotoxicity (LC(50)) were determined by protein staining with sulforhodamin
      B (SRB) and by trypan blue exclusion, respectively. DNA damage--both strand
      breaks and oxidised purines--was quantified by comet assay. Depletion of
      glutathione was measured in a kinetic assay, based on 5-thio-2-nitrobenzoate
      (TNB) formation. For CHX, a moderate cytotoxicity was observed after 1h
      incubation in V79 cells (LC(50): 4.75mM). The 2-alkenals ((E)-2-octenal (OCTE),
      (2E,4Z)-2,4-hexadienal (HEXDI), (E)-2-nonenal (NONE), (2E,6Z)-2,6-nonadienal
      (NONDI)) exhibited a distinctly higher cytotoxicity, except for (E)-2-hexenal
      (HEX) (LC(50): 3.67mM) and cinnamaldehyde (CA) (LC(50): 4.45mM). If the
      incubation time was prolonged to 24h, an IC(50) of 15microM was obtained for CHX
      which is well within the range obtained for the 2-alkenals (4 and 17microM).
      Concentration-dependent DNA damage was observed after 1h incubation with CHX. The
      respective DC(50) values (concentration inducing DNA damage in 50% of cells) were
      272microM (V79) and 455microM (Caco-2). All 2-alkenals were more active under
      these conditions, except for CA. In primary human colon cells, CHX (800microM,
      30min) exhibited a weak, but still significant DNA-damaging potential.
      Glutathione levels in V79 cells were effectively depleted (down to approximately
      20%) by CHX concentrations not yet inducing DNA damage (c < or = 50microM).
      Incubation with CHX or 2-alkenals (50 and 100microM, 1h), followed by H2O2
      treatment (5min, 25microM) resulted in increased levels of oxidised purines in
      the modified comet assay. CHX and HEX, additionally tested in primary human colon
      cells, depleted glutathione and increased the sensitivity towards oxidative
      stress.

PMID- 11525923
TI  - Influence of cytotoxicity and compound precipitation on test results in the
      alkaline comet assay.
AB  - We use the comet assay as part of our genotoxicity screening battery for newly
      synthesized drug candidates. A dataset of more than 250 tests carried out with 75
      drug candidates of various chemical classes was analyzed to elucidate the
      influence of cytotoxicity and compound precipitation on DNA migration in the
      comet assay. Using a V79 Chinese hamster cell line, 38 of the compounds were
      negative and 37 were positive in the comet assay. The reproducibility of test
      results between repeat experiments was 85%. Data on 72 tests with a negative call
      in which the compounds were tested up to highly cytotoxic concentrations
      demonstrated that cytotoxicity, as determined by Trypan blue dye exclusion and
      occurrence of cells with completely fragmented chromatin, did not lead to false
      positive test results. The majority (64.2%) of compounds with a positive call
      induced elevated DNA migration in the absence of excessive cytotoxicity. Compound
      precipitation was observed in 84 tests. In 88.1% of these cases, the test result
      at the precipitating concentration did not differ from that found at the highest
      soluble concentration. Half of the remaining 11.9% of contrary results (most of
      them weak effects) were not reproducible in the respective repeat experiment,
      indicating no or only a negligible influence of precipitation on test results.
      The data indicate that using V79 cells, the comet assay specifically detects
      genotoxic effects and is not confounded by cytotoxicity or compound precipitation
      under the conditions used.

PMID- 11525924
TI  - Antioxidative and antimutagenic activity of yeast cell wall mannans in vitro.
AB  - Antioxidative and antimutagenic effect of yeast cell wall mannans, in particular,
      extracellular glucomannan (EC-GM) and glucomannan (GM-C.u.) both from Candida
      utilis, mannan from Saccharomyces cerevisiae (M-S.c.) and mannan from Candida
      albicans (M-C.a.) was evaluated. Luminol-dependent photochemical method using
      trolox as a standard showed that EC-GM, GM-C.u., M-S.c. and M-C.a. have
      relatively good antioxidative properties. EC-GM exhibited the highest
      antioxidative activity, followed by GM-C.u. and M-S.c. M-C.a. showed the least
      antioxidative activity. These mannans were experimentally confirmed to exhibit
      different, statistically significant antimutagenic activity in reducing damage of
      chloroplast DNA of the flagellate Euglena gracilis induced by ofloxacin and
      acridine orange (AO). We suggest that the antimutagenic effect of EC-GM, GM-C.u.,
      M-S.c. and M-C.a. against ofloxacin is based on their ability to scavenge
      reactive oxygen radicals. With AO, the reduction of the chloroplast DNA lession
      could be a result of the absorptive capacity of the mannans. The important
      characteristics of mannans isolated from the yeast cell walls, such as good water
      solubility, relatively small molecular weight (15-30kDa), and antimutagenic
      effect exerted through different mode of action, appear to be a promising
      features for their prospective use as a natural protective (antimutagenic)
      agents.

PMID- 11525925
TI  - Metabolic activation of carcinogenic 1-nitropyrene by human cytochrome P450 1B1
      in Salmonella typhimurium strain expressing an O-acetyltransferase in SOS/umu
      assay.
AB  - Metabolic activation of 1-nitropyrene (1-NP) by human cytochrome P450 (P450)
      family 1 enzymes co-expressed with NADPH-cytochrome P450 reductase (NPR) in
      Escherichia coli membranes was investigated. 1-NP induced umu gene expression in
      Salmonella typhimurium TA1535/pSK1002 in the absence of any P450 system, but the
      activities were influenced by the levels of bacterial O-acetyltransferase (OAT)
      and nitroreductase. Metabolic activation of 1-NP by human P450 1B1/NPR membranes
      was observed and was influenced by the levels of OAT levels in tester strains.
      Metabolic activation of 1-NP (0.3microM) by P450 1B1 was 750 umu units/min/nmol
      P450 1B1 in an OAT-overexpressing strain NM2009. The metabolic activation of 1-NP
      (3-30microM) was similar (approximately 300 umu units/min/nmol P450 1B1) using
      TA1535/pSK1002 or OAT-deficient strain NM2000. P450 1B1 had the highest catalytic
      activities among P450 family 1 enzymes for the activation of 1-aminopyrene (1-AP)
      in the OAT-overexpressing strain NM2009, suggesting nitrenium ion formation via N
      hydroxylation/O-acetylation. High-performance liquid chromatography (HPLC)
      analyses revealed the formation of 1-nitropyrene-6-ol and also 1-nitropyrene-3
      ol, 1-nitropyrene-8-ol, and trans-4,5-dihydroxy-4,5-diol-1-nitropyrene from 1-NP
      (10microM), catalyzed by P450 1B1. These results indicate that 1-NP can be
      activated by human P450 1B1 to a genotoxic agent by nitroreduction/O-acetylation
      at low substrate concentrations and probably by epoxidation (independent of OAT)
      at high concentrations.

PMID- 11525927
TI  - Cytokines and sickness behavior: implications from knockout animal models.

PMID- 11525926
TI  - HLA associations in type 1 diabetes: merging genetics and immunology.

PMID- 11525928
TI  - Monomeric IgE regulates mast-cell survival.

PMID- 11525929
TI  - Surviving without a TCR.

PMID- 11525938
TI  - The ependymal route to the CNS: an emerging gene-therapy approach for MS.
AB  - The systemic administration of anti-inflammatory molecules to patients affected
      by immune-mediated inflammatory demyelinating diseases of the central nervous
      system (CNS), such as multiple sclerosis, has limited therapeutic efficacy owing
      to the presence of the blood-brain barrier. The delivery of drugs to the CNS
      using a nonreplicative viral vector engineered with genes encoding anti
      inflammatory cytokines might represent an alternative therapeutic strategy. Here,
      we propose accessing the CNS through the ependymal-leptomeningeal route. This
      approach is based on the injection of nonreplicative vectors into the
      cerebrospinal fluid space. These vectors are able to infect the ependymal and
      leptomeningeal cells consistently and without side effects, and in turn, produce
      the 'therapeutic' product of the transgene in the CNS for extended periods of
      time. This strategy could represent an alternative treatment for inflammatory
      neurological disorders when systemic immunosuppressive therapies fail to control
      the evolution of disease satisfactorily.

PMID- 11525939
TI  - PI 3-K and T-cell activation: limitations of T-leukemic cell lines as signaling
      models.
AB  - Phosphoinositide 3-kinases (PI 3-Ks) phosphorylate the d3-hydroxyl position of
      phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P(2)] resulting in the
      generation of the 3'-phosphoinositide lipid PtdIns(3,4,5)P(3). PI 3-Ks are
      activated by a diverse set of receptors that play a role in determining T-cell
      function. It now seems that leukemic T cells, which are widely used as models for
      T-cell biology, show constitutive activation of PI 3-K-mediated signal
      transduction pathways. Hence, studies of the role of PI 3-K in T-cell biology
      using leukemic cell lines might have misinterpreted the importance of this
      pathway for T-cell signal transduction.

PMID- 11525940
TI  - Bacterial superantigens: provocateurs of gut dysfunction and inflammation?
AB  - Inflammatory bowel diseases (IBDs) are chronic debilitating conditions, which
      impair the patient's quality of life significantly. Among them, Crohn's disease
      and ulcerative colitis are idiopathic disorders for which an infective etiology
      has long been sought. Here, we present an opinion in support of the hypothesis
      that bacterial superantigens can participate in the initiation, exaggeration or
      reactivation of enteric inflammatory disease, at least in some patients. Although
      the identification of a specific pathogen responsible for IBD remains a worthy
      pursuit, an awareness of the response to bacterial products per se will be of
      value in providing a comprehensive understanding of enteric pathophysiological
      mechanisms and their potential role in IBDs.

PMID- 11525941
TI  - Cytokine fields and the polarization of the immune response.
AB  - Certain cells that participate in the immune response are known to become
      polarized in their production of cytokines. It is postulated that, after initial
      polarization at the site of antigenic encounter, the different types of cell
      arriving at this site are induced to conform to the local cytokine field,
      implying that they share common regulatory circuits. As they migrate, these cells
      might, in turn, spread the particular cytokine field. Therefore, the field is
      'infectious' in nature. Propagation of the cytokine field must be regulated
      somehow. The invasion of the cytokine field into an organ or the entire body
      could have major immunological consequences.

PMID- 11525942
TI  - Inflammation in autoimmunity: receptors for IgG revisited.
AB  - During the past decade, our knowledge of Fc receptor interactions in inflammation
      has increased dramatically owing to the availability of single and multiple Fc
      receptor-deficient mice. The deletion of activating Fc gamma receptors protects
      against inflammation in models of immune-complex-mediated diseases, whereas the
      deletion of inhibitory Fc gamma receptors triggers increased susceptibility to
      immune-complex-induced inflammation. These new insights have a profound impact on
      our understanding of inflammation in autoimmune diseases, such as systemic lupus
      erythematosus (SLE). Comprehending the complex interactions between activating
      and inhibitory Fc gamma receptors might lead to new therapeutic approaches for
      human diseases, including SLE.

PMID- 11525943
TI  - From cancer genomics to cancer immunotherapy: toward second-generation tumor
      antigens.
AB  - Clinically successful specific cancer immunotherapy depends on the identification
      of tumor-rejection antigens (Ags). Historically, tumor Ags have been identified
      by analyzing either T-cell or antibody responses of cancer patients against the
      autologous cancer cells. The unveiling of the sequence of the human genome,
      improved bioinformatics tools and optimized immunological analytical tools have
      made it possible to screen any given protein for immunogenic epitopes.
      Overexpressed genes in cancer can be identified by gene-expression profiling;
      immunogenic epitopes can be predicted based on HLA-binding motifs; candidate
      peptides can be identified by mass spectrometry of tumor-cell-derived HLA
      molecules; and peptide-specific T cells can be qualitatively and quantitatively
      analyzed at the single-cell level using ELISPOT and tetramer technologies. Here,
      we suggest that, based on these advancements, a new class of tumor Ags can be
      identified by directly linking cancer genomics to cancer immunology and
      immunotherapy.

PMID- 11525944
TI  - Fragile histidine triad gene and skin cancer.
AB  - Five years ago the fragile histidine triad (FHIT) gene including the most common
      fragile site locus of the human genome, FRA3B, was identified. The gene is
      altered in many types of cancer and several data support the idea that FHIT has
      to be considered a tumor suppressor. FHIT abnormalities were investigated in some
      skin tumors. Fifty-seven per cent of Merkel cell carcinomas displayed abnormal
      FHIT products but the involvement of FHIT in human non-melanoma skin cancer is
      still unclear. Because the murine Fhit locus is similar to its human homologue
      and is altered in cancer cell lines, we have established a strain of Fhit
      deficient mice. After N-nitrosomethylbenzylamine treatment, the spectrum of
      tumors developed by the Fhit-deficient mice was similar to those observed in a
      familial skin cancer condition, the Muir-Torre syndrome, although there is no
      clear evidence yet for a relationship of FHIT and the human syndrome. Because
      cancer cells lacking in FHIT are defective in apoptosis, we propose the Fhit
      deficient mouse as a model to understand a possible proapoptotic mechanism
      deficiency in the human syndrome.

PMID- 11525945
TI  - Treatment of alopecia areata in C3H/HeJ mice with the topical immunosuppressant
      FK506 (Tacrolimus).
AB  - Alopecia areata-like hair loss has been observed in C3H/HeJ mice and can be
      defined as a tissue-restricted T cell mediated disease of the hair follicle.
      Because FK506 has been described as suppressing T cell mediated autoimmune
      diseases, we addressed the question whether topical treatment of C3H/HeJ mice
      with FK506 has a beneficial effect on alopecia areata (AA). For this purpose six
      C3H/HeJ mice with AA were treated topically with 0.1% FK506 ointment, four mice
      received the vehicle only. Four of six FK506-treated mice showed complete hair
      regrowth, whereas 1/4 vehicle-treated mice regrew hair. Mice treated successfully
      with FK506 had reduced perifollicular infiltrates of CD4+ and CD8+ cells and a
      decreased expression of MHC class I and II and ICAM-1 on hair follicle
      epithelium, compared to control mice. We conclude that topical treatment with
      FK506 is able to induce hair regrowth in AA of C3H/HeJ mice, most likely by
      suppressing the T cell mediated immune response.

PMID- 11525946
TI  - CD8+ cell changes in psoriasis associated with roxithromycin-induced clinical
      improvement.
AB  - We have shown that T cell receptor BV2- and BV8-bearing CD8+ cells are decreased
      in the peripheral blood of psoriatic patients, while T cells possessing these BVs
      accumulate in psoriatic lesions. T cells homing to skin express cutaneous
      lymphocyte-associated antigen (CLA), and bacterial superantigens that trigger
      psoriasis promote this expression. Roxithromycin has immunomodulatory potency and
      its effectiveness for psoriasis has been proposed. Therefore, we monitored BV
      usage and alteration of superantigen-promoted CLA expression in circulating CD8+
      cells of psoriatics before and after roxithromycin therapy. After roxithromycin
      treatment, circulating BV2- and BV8-bearing CD8+ cells were increased and CD8+
      cells exhibited reduced expression of CLA when stimulated in vitro with bacterial
      superantigens. It is suggested that roxithromycin downregulates augmented
      expression of CLA by CD8+ cells, thereby suppressing their skin-homing and
      elevating the numbers of circulating BV2- and BV8-positive CD8+ cells. Such
      events may be included in part in the improvement of psoriasis with
      roxithromycin.

PMID- 11525947
TI  - Evaluation of skin susceptibility to irritancy by routine patch testing with
      sodium lauryl sulfate.
AB  - Irritant patch testing with sodium lauryl sulfate (SLS) will become more and more
      a routine test determining skin susceptibility in men. Recently, it has been
      shown that for practical reasons, irritant SLS patch testing can take place on
      the back simultaneously with a routine allergic patch test to other contact
      allergens. However, SLS patch testing has mostly been performed on the forearm in
      studying experimental skin irritation so far. The aim of this study was to
      determine whether there is a relationship in skin response to aqueous SLS
      (0.125%; 0.25%; 0.5% and 1.0%) between the forearm and the back assessed by
      visual scoring and measurement of transepidermal water loss (TEWL). We found a
      pronounced reaction of the forearm compared to the back. TEWL values as well as
      visual scores correlated well with SLS concentration. There was also a high
      correlation in visual scoring between the forearm and the back. Based on test
      sensitivity and specificity we suggest a 48 hrs patch test for routine screening
      with 0.5% SLS on the forearm evaluated by TEWL measurement or visual scoring 24
      hrs after patch removal. A mild erythema (scored as < or =1) is considered to be
      normal. If for practical reasons, the SLS patch is placed on the back
      simultaneously with the allergic patch test, 0.5% SLS may be sufficient, too.
      TEWL measurement so far provides a reliable method and will certainly be
      necessary for experimental studies on irritant skin reactions, particularly when
      different SLS concentrations are used. After a 48 hrs patch test with SLS 0.5%
      TEWL measurement should be performed at 72 hrs. A value of < or =31.6 g/m(2)hr
      seems to follow the normal distribution.

PMID- 11525948
TI  - Coordinate expression of membrane type-matrix metalloproteinases-2 and 3 (MT2-MMP
      and MT3-MMP) and matrix metalloproteinase-2 (MMP-2) in primary and metastatic
      melanoma cells.
AB  - Expression of MMP-2 in melanoma cells has been demonstrated to be involved in the
      degradation of extracellular matrix during melanoma growth and to correlate with
      later melanoma metastasis. MMP-2 is considered to be activated by membrane
      associated matrix metalloproteinases (MT-MMPs). To know whether MT-MMPs are
      involved in the activation of MMP-2 in melanoma cells, immunohistochemical
      studies were performed in primary and metastatic melanoma by use of the
      antibodies for MT1-MMP, MT2-MMP and MT3-MMP. Expression of MT1-MMP, MT2-MMP, MT3
      MMP and MMP-2 in nevocellular nevus (n = 5), dysplastic nevus (n = 2) and
      juvenile melanoma (n = 3) was undetectable or detected in only a few cells.
      Superficial spreading melanoma (SSM) (n = 3) and acral lentiginous melanoma (ALM)
      (n = 3) showed a moderate expression of MT1 approximately 3-MMP. In nodular
      melanoma (NM) (n = 2) and metastatic melanoma (n = 3), MT1 approximately 3-MMP
      was more intensely expressed. Double immunofluorescence demonstrated a consistent
      colocalization of MT2-MMP/MMP-2 and MT3-MMP/MMP-2 in the NM and metastatic
      melanoma cells. The colocalization of MT2,3-MMP and MMP-2 in nodular and
      metastatic melanoma cells suggests that MT-MMPs and MMP-2 co-operate in the
      invasive and metastatic process of melanoma cells.

PMID- 11525949
TI  - Expression of TGF-beta and its receptors in murine fetal and adult dermal wounds.
AB  - The transforming growth factor-betas (TGF-betas) are of major importance in wound
      healing and have been implicated in the scar-less wound repair observed in
      fetuses. Few studies have characterised the role of TGF-beta in fetal wound
      repair and to date no studies have characterised the expression of its receptors
      within non-scarring fetal wounds. We have localised the TGF-beta isoforms beta1,
      beta2 and beta3 and its two receptors, TGF-betaRI and TGF-betaRII in both adult
      and fetal dermal murine wounds. We observed low level immunofluorescence of TGF
      beta1 and TGF-beta2 in fetal wounds and although TGF-beta3 staining was observed
      in the epidermis of fetal skin, there was no upregulation in response to injury.
      By contrast, all three isoforms were strongly expressed in adult wounds. Similar
      to its ligands, TGF-beta receptor expression was increased post-wounding in the
      adult wounds. However, in contrast, no mRNA or protein for either of the TGF-beta
      receptors was observed in response to wounding in the fetal dermis although there
      was both mRNA and protein expression of both the receptors localised within the
      fetal alimentary tract, one of the few fetal organs which does scar post-injury.
      The differences that we observed in the expression of TGF-beta and its receptors
      in adult and fetal wounds could be important in the absence of scar formation
      that is observed in the fetus.

PMID- 11525950
TI  - Interest of PS100 assay when (99m)Tc sestamibi scintigraphy failed to identify
      lymph node metastases of melanoma.
AB  - The study evaluated the contribution of serum PS100 assay to the detection of
      lymph node metastases during the follow-up of patients previously treated for a
      malignant melanoma, in addition to (99m)Tc sestamibi (MIBI) scintigraphy and
      investigation for gene MDR1, in order to detect chemoresistance phenomena. The
      study included 37 patients with a clinically questionable lymph node around basin
      lymphatic areas of the previously surgically-treated malignant melanoma. The
      sensitivity and specificity of PS100 assay were 91% and 86.5%, respectively. The
      sensitivity and specificity of MIBI scintigraphy were 95% and 85%, respectively.
      Overexpression of gene MDR1 was observed in six cases. In the event of negative
      scintigraphic findings, the concomitant analysis of PS100 levels and the
      scintigraphic result enabled the metastatic MDR+ patients to be distinguished
      from the non-metastatic patients. PS100 assay may therefore be proposed for the
      follow-up of malignant melanoma.

PMID- 11525951
TI  - Resurfacing CO2 laser treatment of linear verrucous epidermal nevus.
AB  - The term linear epidermal nevus (LVEN) refers to benign hyperplasia of the
      epidermis. Three types of LVEN can be distinguished: localized, systemic and
      inflammatory form. All have in common resistance to treatment and risk of
      recurrence. We report the observations of 5 patients with inflammatory linear
      verrucous epidermal nevus and 5 patients with linear verrucous epidermal nevus.
      Management by superpulsed CO2 laser was performed as follows: test treatment,
      completed by removal of the lesion in one or more sessions. Treatment was
      effective in all cases but 2. Satisfactory cosmetic results were obtained; slight
      hyperpigmentation, transitory desquamation and erythematous papules were
      observed. There was no recurrence in two years follow-up. We suppose that for the
      two patients with recurrence, our treatment failure is due to the lower laser
      parameters used in these patients compared to the others, because of their
      younger age.

PMID- 11525952
TI  - Persistent urticaria--urticarial reaction caused by late phase reaction?
AB  - In ordinary urticaria, individual lesions disappear within 24 hours. We
      encountered 3 patients who showed urticarial reactions lasting more than 24
      hours. In all patients, skin biopsy revealed interstitial dermal edema and a
      perivascular infiltration predominated by eosinophils, without immunoglobulins or
      complement deposition, or endothelial fibrinoid degeneration. Their eosinophil
      counts and serum complement levels were within normal range. No proteinurea or
      joint pain was observed. They could not be controlled by any medications except
      for glucocorticoid. These findings indicate our cases are not ordinary urticaria,
      urticarial reaction accompanied by eosinophilia, urticarial vasculitis or delayed
      pressure urticaria. We recognize such urticarial reaction as a different clinical
      entity from the usual urticaria, and we speculate that this condition is caused
      by late phase reaction because of the clinical course and eosinophil
      infiltrations.

PMID- 11525953
TI  - Frequency and relevance of positive patch tests to cyclohexylthiophthalimide, a
      new rubber allergen.
AB  - Cyclohexylthiophtalimide (CTP) is currently the most widely used vulcanization
      retarder in the rubber industry. Little is known about sensitization to CTP,
      although positive tests to it do occur in patients exposed to rubber objects. A
      retrospective study of 350 patients who were patch tested with the standard
      rubber chemical series was conducted in two departments of dermatology, one in
      Nancy, France, and one in Leuven, Belgium. Sixteen (4.6%) out of the 350 patients
      had clear and 6 (1.7%) had doubtful positive reactions to CTP. Cross-sensitivity
      with other molecules could not be determined. The source of sensitization in most
      cases seems to have been protective rubber gloves at work. In the other cases,
      sensitization was suspected to have been caused by rubber shoes, elastic bands in
      underwear, or other rubber objects. The determination of the relevance of
      positive tests remains difficult, especially since little is known about the
      components of rubber products.

PMID- 11525954
TI  - Five cases of melanoma in HIV positive patients.
AB  - BACKGROUND: Kaposi's sarcoma, high grade B-cell non-Hodgkin lymphoma and invasive
      carcinoma of the cervix are all AIDS-defining illnesses according to the CDC
      staging criteria classification. A number of other malignancies, not
      traditionally associated with HIV infection, such as Hodgkin's disease, cancers
      of the rectum, anus, and germ-cell tumours, appear to occur more often than would
      be expected in these patients. Malignant cutaneous lesions, including basal cell,
      squamous-cell carcinomas, Bowen's disease, and cutaneous melanoma (CM) have been
      less often reported. PATIENTS AND METHODS: We retrospectively evaluated the
      clinical data of 5 HIV+ seropositive patients and CM observed at the "M.
      Bufalini" Hospital, Cesena, Italy from 1994 to 2000. RESULTS: All the 5 subjects
      had a history of intense sun exposure and sunburns. Four patients reported
      homosexuality as their risk factor for HIV disease. Reviewing the international
      literature on the subject HIV infected homosexuals appear the group at higher
      risk of developing CMM, accounting for 80% of cases. CONCLUSION: As patients'
      life expectancy appears to be prolonged after the advent of the HAART therapy,
      skin cancers will probably become more frequent in the near future. Clinicians
      should keep close medical surveillance to promptly diagnose new cases of melanoma
      and non-melanoma skin cancers and advise their HIV-infected patients on the risk
      of prolonged sun exposure and severe sun burns for the development of skin
      cancers.

PMID- 11525955
TI  - Cutaneous ulceration as a sign of methotrexate toxicity.
AB  - Methotrexate (MTX) inhibits DNA synthesis by competition with dihydrofolate
      reductase. Adverse cutaneous reactions to MTX are usually dose-related and have
      been mainly reported in patients receiving extremely large doses of chemotherapy.
      Painful erosion of psoriatic plaques has been often reported as an early sign of
      MTX toxicity, but cutaneous ulceration as a sign of MTX toxicity in patients
      without psoriasis has only been described in one case. We report a patient with
      rheumatoid arthritis and without psoriasis who developed cutaneous ulceration on
      the knuckles as a sign of MTX toxicity. Cutaneous ulceration by MTX toxicity is
      an exclusion diagnosis and its pathogenic mechanism may be multifactorial,
      including direct toxicity of the drug in addition to local factors.

PMID- 11525956
TI  - Costello syndrome: report of a new case with choanal atresia and fatal outcome.
AB  - We describe a girl with motor and mental retardation, macrocephaly, a "coarse"
      face, choanal atresia, postnatal feeding difficulty, redundant skin with deep
      palmar and plantar creases, and histopathological evidence of altered elastic
      fibers, who died at the age of 11 months. We believe this represents another case
      of Costello syndrome. Lacking papillomata, she had choanal atresia and underwent
      a fatal outcome at an early age. The differential diagnosis of cutis laxa in
      association with postnatal growth retardation and developmental delay and with
      cardio-facio-cutaneous and Noonan syndromes is discussed.

PMID- 11525957
TI  - Cutaneous necrobiotic xanthogranuloma (NXG)--successfully treated with low dose
      chlorambucil.
AB  - We report a case of necrobiotic xanthogranuloma in a 51 year-old white male
      patient presenting with a 6-year history of multiple indurated violaceous nodules
      and plaques involving the eyelids, trunk and extremities. He had an associated
      paraproteinemia (Ig G lambda), elevated sedimentation rate, cryoglobulinemia and
      hypocomplementemia. No extracutaneous involvement was detected. He was
      successfully treated with chlorambucil (2 mg/d for 7 months), leading to
      disappearance of all skin lesions.

PMID- 11525958
TI  - Human papillomavirus associated Bowen's disease of the foot: unique clinical
      features mimicking a common wart.
AB  - We describe a case of Bowen's disease that developed on the left dorsal foot of a
      56-year-old female patient and that mimicked the clinical features of a common
      wart. PCR-based analysis indicated that the lesion contained HPV-16 DNA and HPV
      16 positive cells were found in the upper layers of the epidermal lesion using in
      situ hybridization with an HPV-16 probe.

PMID- 11525959
TI  - Acquired reactive perforating collagenosis.
AB  - Acquired perforating disorder has been recognized as an uncommon distinct
      dermatosis in which altered collagen is eliminated through the epidermis. Several
      disorders accompanied by itching and scratching were reported to be associated
      with reactive perforating collagenosis. A 67-year-old white woman diagnosed as
      acquired reactive perforating collagenosis with poorly controlled diabetes
      mellitus and congestive cardiac failure is presented.

PMID- 11525960
TI  - Acute exanthematous pustular drug eruption induced by mexiletine.
AB  - A 56-year-old man developed infiltrated erythemas on the trunk, extremities, and
      face with marked facial edema, one month after taking mexiletine hydrochloride
      for his arrhythmia. A number of pustules were also noted on the surface of
      erythemas on his chest and face. Laboratory examination showed liver dysfunction
      and hypereosinophilia. The culture from pustules was sterile. Histological
      examination of the biopsied skin from a pustular lesion revealed a subcorneal
      abscess, and perivascular infiltration of lymphocytes, mononuclear cells and
      eosinophils in the upper dermis. The skin lesions and facial edema as well were
      improved within three weeks by withdrawal of mexiletine hydrochloride. Patch
      tests with 10% and 20% mexiletine hydrochloride in petrolatum showed positive
      reaction, however, pustules were not provoked on the tested site. We conclude
      that pustules, infiltrated erythema and facial edema were the signs of acute
      exanthematous pustular drug eruption induced by mexiletine hydrochloride.

PMID- 11525961
TI  - Guess what! Multiple disseminated dermatofibromas in a woman with systemic lupus
      erythematosus.

PMID- 11525962
TI  - Guess what! Malignant metastatic melanoma presenting with generalized melanosis
      and melanuria.

PMID- 11525963
TI  - Guess what! Diffuse psoriasiform eruption in a young adult.

PMID- 11525964
TI  - Guess what! Tinea capitis by Trichophyton schoenleinii.

PMID- 11525965
TI  - Dermoscopy of pigmented skin lesions (Part II).

PMID- 11525966
TI  - Measurement of denitrification in sediments with the 15N isotope pairing
      technique.

PMID- 11525967
TI  - Distribution and diversity of symbiotic thermophiles, Symbiobacterium
      thermophilum and related bacteria, in natural environments.
AB  - Symbiobacterium thermophilum is a tryptophanase-positive thermophile which shows
      normal growth only in coculture with its supporting bacteria. Analysis of the 16S
      rRNA gene (rDNA) indicated that the bacterium belongs to a novel phylogenetic
      branch at the outermost position of the gram-positive bacterial group without
      clustering to any other known genus. Here we describe the distribution and
      diversity of S. thermophilum and related bacteria in the environment.
      Thermostable tryptophanase activity and amplification of the specific 16S rDNA
      fragment were effectively employed to detect the presence of Symbiobacterium.
      Enrichment with kanamycin raised detection sensitivity. Mixed cultures of
      thermophiles containing Symbiobacterium species were frequently obtained from
      compost, soil, animal feces, and contents in the intestinal tracts, as well as
      feeds. Phylogenetic analysis and denaturing gradient gel electrophoresis of the
      specific 16S rDNA amplicons revealed a diversity of this group of bacteria in the
      environment.

PMID- 11525968
TI  - Identification and characterization of bacteria in a selenium-contaminated
      hypersaline evaporation pond.
AB  - Solar evaporation ponds are commonly used to reduce the volume of seleniferous
      agricultural drainage water in the San Joaquin Valley, Calif. These hypersaline
      ponds pose an environmental health hazard because they are heavily contaminated
      with selenium (Se), mainly in the form of selenate. Se in the ponds may be
      removed by microbial Se volatilization, a bioremediation process whereby toxic,
      bioavailable selenate is converted to relatively nontoxic dimethylselenide gas.
      In order to identify microbes that may be used for Se bioremediation, a 16S
      ribosomal DNA phylogenetic analysis of an aerobic hypersaline pond in the San
      Joaquin Valley showed that a previously unaffiliated group of uncultured bacteria
      (belonging to the order Cytophagales) was dominant, followed by a group of
      cultured gamma-Proteobacteria which was closely related to Halomonas species. Se
      K-edge X-ray absorption spectroscopy of selenate-treated bacterial isolates
      showed that they accumulated a mixture of predominantly selenate and a
      selenomethionine-like species, consistent with the idea that selenate was
      assimilated via the S assimilation pathway. One of these bacterial isolates
      (Halomonas-like strain MPD-51) was the best candidate for the bioremediation of
      hypersaline evaporation ponds contaminated with high Se concentrations because it
      tolerated 2 M selenate and 32.5% NaCl, grew rapidly in media containing selenate,
      and accumulated and volatilized Se at high rates (1.65 microg of Se g of protein(
      1) x h(-1)), compared to other cultured bacterial isolates.

PMID- 11525969
TI  - Light conditions affect the measurement of oceanic bacterial production via
      leucine uptake.
AB  - The effect of irradiance in the range of 400 to 700 nm or photosynthetically
      active radiation (PAR) on bacterial heterotrophic production estimated by the
      incorporation of 3H-leucine (referred to herein as Leu) was investigated in the
      northwestern Mediterranean Sea and in a coastal North Atlantic site, with Leu
      uptake rates ranging over 3 orders of magnitude. We performed in situ incubations
      under natural irradiance levels of Mediterranean samples taken from five depths
      around solar noon and compared them to incubations in the dark. In two of the
      three stations large differences were found between light and dark uptake rates
      for the surface most samples, with dark values being on average 133 and 109%
      higher than in situ ones. Data obtained in coastal North Atlantic waters
      confirmed that dark enclosure may increase Leu uptake rates more than threefold.
      To explain these differences, on-board experiments of Leu uptake versus
      irradiance were performed with Mediterranean samples from depths of 5 and 40 m.
      Incubations under a gradient of 12 to 1,731 micromol of photons m(-2) x s(-1)
      evidenced a significant increase in incorporation rates with increasing PAR in
      most of the experiments, with dark-incubated samples departing from this pattern.
      These results were not attributed to inhibition of Leu uptake in the light but to
      enhanced bacterial response when transferred to dark conditions. The ratio of
      dark to light uptake rates increased as dissolved inorganic nitrogen
      concentrations decreased, suggesting that bacterial nutrient deficiency was
      overcome by some process occurring only in the dark bottles.

PMID- 11525970
TI  - Comparison of pmoA PCR primer sets as tools for investigating methanotroph
      diversity in three Danish soils.
AB  - Three particulate methane monooxygenase PCR primer sets (A189-A682, A189-A650,
      and A189-mb661) were investigated for their ability to assess methanotroph
      diversity in soils from three sites, i.e., heath, oak, and sitka, each of which
      was capable of oxidizing atmospheric concentrations of methane. Each PCR primer
      set was used to construct a library containing 50 clones from each soil type. The
      clones from each library were grouped by restriction fragment length
      polymorphism, and representatives from each group were sequenced and analyzed.
      Libraries constructed with the A189-A682 PCR primer set were dominated by amoA
      related sequences or nonspecific PCR products with nonsense open reading frames.
      The primer set could not be used to assess methanotroph diversity in these soils.
      A new pmoA-specific primer, A650, was designed in this study. The A189-A650
      primer set demonstrated distinct biases both in clone library analysis and when
      incorporated into denaturing gradient gel electrophoresis analysis. The A189
      mb661 PCR primer set demonstrated the largest retrieval of methanotroph diversity
      of all of the primer sets. However, this primer set did not retrieve sequences
      linked with novel high-affinity methane oxidizers from the soil libraries, which
      were detected using the A189-A650 primer set. A combination of all three primer
      sets appears to be required to examine both methanotroph diversity and the
      presence of novel methane monooxygenase sequences.

PMID- 11525971
TI  - Genotypic analyses of Escherichia coli O157:H7 and O157 nonmotile isolates
      recovered from beef cattle and carcasses at processing plants in the Midwestern
      states of the United States.
AB  - Escherichia coli O157:H7 and O157 nonmotile isolates (E. coli O157) previously
      were recovered from feces, hides, and carcasses at four large Midwestern beef
      processing plants (R. O. Elder, J. E. Keen, G. R. Siragusa, G. A. Barkocy
      Gallagher, M. Koohmaraie, and W. W. Laegreid, Proc. Natl. Acad. Sci. USA 97:2999
      3003, 2000). The study implied relationships between cattle infection and carcass
      contamination within single-source lots as well as between preevisceration and
      postprocessing carcass contamination, based on prevalence. These relationships
      now have been verified based on identification of isolates by genomic
      fingerprinting. E. coli O157 isolates from all positive samples were analyzed by
      pulsed-field gel electrophoresis of genomic DNA after digestion with XbaI.
      Seventy-seven individual subtypes (fingerprint patterns) grouping into 47 types
      were discerned among 343 isolates. Comparison of the fingerprint patterns
      revealed three clusters of isolates, two of which were closely related to each
      other. Remarkably, isolates carrying both Shiga toxin genes and nonmotile
      isolates largely fell into specific clusters. Within lots analyzed, 68.2% of the
      postharvest (carcass) isolates matched preharvest (animal) isolates. For
      individual carcasses, 65.3 and 66.7% of the isolates recovered postevisceration
      and in the cooler, respectively, matched those recovered preevisceration.
      Multiple isolates were analyzed from some carcass samples and were found to
      include strains with different genotypes. This study suggests that most E. coli
      O157 carcass contamination originates from animals within the same lot and not
      from cross-contamination between lots. In addition, the data demonstrate that
      most carcass contamination occurs very early during processing.

PMID- 11525972
TI  - Fate and dissemination of Bacillus subtilis spores in a murine model.
AB  - Bacterial spores are being consumed as probiotics, although little is known about
      their efficacy or mode of action. As a first step in characterizing spore
      probiotics, we have studied the persistence and dissemination of Bacillus
      subtilis spores given orally to mice. Our results have shown that spores do not
      appear to disseminate across the mucosal surfaces. However, we found that the
      number of spores excreted in the feces of mice was, in some experiments, larger
      than the original inoculum. This was an intriguing result and might be explained
      by germination of a proportion of the spore inoculum in the intestinal tract,
      followed by limited rounds of cell growth and then sporulation again. This result
      raises the interesting question of whether it is the spore or the germinated
      spore that contributes to the probiotic effect of bacterial spores.

PMID- 11525973
TI  - Induction of phase variation events in the life cycle of the marine
      coccolithophorid Emiliania huxleyi.
AB  - Emiliania huxleyi is a unicellular marine alga that is considered to be the
      world's major producer of calcite. The life cycle of this alga is complex and is
      distinguished by its ability to synthesize exquisitely sculptured calcium
      carbonate cell coverings known as coccoliths. These structures have been targeted
      by materials scientists for applications relating to the chemistry of biomedical
      materials, robust membranes for high-temperature separation technology,
      lightweight ceramics, and semiconductor design. To date, however, the molecular
      and biochemical events controlling coccolith production have not been determined.
      In addition, little is known about the life cycle of E. huxleyi and the
      environmental and physiological signals triggering phase switching between the
      diploid and haploid life cycle stages. We have developed laboratory methods for
      inducing phase variation between the haploid (S-cell) and diploid (C-cell) life
      cycle stages of E. huxleyi. Plating E. huxleyi C cells on solid media was shown
      to induce phase switching from the C-cell to the S-cell life cycle stage, the
      latter of which has been maintained for over 2 years under these conditions. Pure
      cultures of S cells were obtained for the first time. Laboratory conditions for
      inducing phase switching from the haploid stage to the diploid stage were also
      established. Regeneration of the C-cell stage from pure cultures of S cells
      followed a predictable pattern involving formation of large aggregations of S
      cells and the subsequent production of cultures consisting predominantly of
      diploid C cells. These results demonstrate the ability to manipulate the life
      cycle of E. huxleyi under controlled laboratory conditions, providing us with
      powerful tools for the development of genetic techniques for analysis of
      coccolithogenesis and for investigating the complex life cycle of this important
      marine alga.

PMID- 11525974
TI  - Contamination of river water by Cryptosporidium parvum oocysts in western Japan.
AB  - In Japan, only a few rivers have been inspected for Cryptosporidium parvum
      contamination, and the methods used had low sensitivity. In 1998 and 1999, we
      used a method with higher sensitivity to examine all large rivers used as sources
      of water supply in one prefecture (which we divided into four areas) in western
      Japan for Cryptosporidium oocysts. One sample was collected at each of 156 sites
      along 18 rivers, and samples were tested for Cryptosporidium oocysts by
      immunomagnetic separation. Samples were classified as being obtained on an island
      with livestock and fishing industries, a densely populated urban area, a western
      region including farming villages, or a still more rural northern area with
      agriculture and fishing. Restriction fragment length polymorphism analysis was
      used for identification of the C. parvum found as the bovine or human type. C.
      parvum was detected in at least one sample from 13 of the 18 rivers and in 47%
      (74 of 156) of the samples. One-third to all of the samples from each area
      contained C. parvum oocysts. The number of C. parvum oocysts per 20 liters of
      river water varied in the same pattern as the number of cattle kept in the four
      kinds of areas (as determined by the Mantel extension test). Oocysts isolated
      were of the bovine type; the C. parvum detected in rivers probably came from
      cattle kept in that valley. As we had expected, when tested with a more sensitive
      method, river water in western Japan was found to be greatly contaminated with C.
      parvum oocysts, as reported in other countries.

PMID- 11525975
TI  - Kinetics and metabolism of cellulose degradation at high substrate concentrations
      in steady-state continuous cultures of Clostridium cellulolyticum on a chemically
      defined medium.
AB  - The hydrolysis and fermentation of insoluble cellulose were investigated using
      continuous cultures of Clostridium cellulolyticum with increasing amounts of
      carbon substrate. At a dilution rate (D) of 0.048 h(-1), biomass formation
      increased proportionately to the cellulose concentration provided by the feed
      reservoir, but at and above 7.6 g of cellulose x liter(-1) the cell density at
      steady state leveled off. The percentage of cellulose degradation declined from
      32.3 to 8.3 with 1.9 and 27.0 g of cellulose x liter(-1), respectively, while
      cellodextrin accumulation rose and represented up to 4.0% of the original carbon
      consumed. The shift from cellulose-limited to cellulose-sufficient conditions was
      accompanied by an increase of both the acetate/ethanol ratio and lactate
      biosynthesis. A kinetics study of C. cellulolyticum metabolism in cellulose
      saturation was performed by varying D with 18.1 g of cellulose x liter(-1).
      Compared to cellulose limitation (M. Desvaux, E. Guedon, and H. Petitdemange, J.
      Bacteriol. 183:119-130, 2001), in cellulose-sufficient continuous culture (i) the
      ATP/ADP, NADH/NAD+, and q(NADH produced)/q(NADH used) ratios were higher and were
      related to a more active catabolism, (ii) the acetate/ethanol ratio increased
      while the lactate production decreased as D rose, and (iii) the maximum growth
      yield (Y(max)X/S) (40.6 g of biomass per mol of hexose equivalent) and the
      maximum energetic yield (Y(max)ATP) (19.4 g of biomass per mol of ATP) were
      lowered. C. cellulolyticum was then able to regulate and optimize carbon
      metabolism under cellulose-saturated conditions. However, the facts that some
      catabolized hexose and hence ATP were no longer associated with biomass
      production with a cellulose excess and that concomitantly lactate production and
      pyruvate leakage rose suggest the accumulation of an intracellular inhibitory
      compound(s), which could further explain the establishment of steady-state
      continuous cultures under conditions of excesses of all nutrients. The following
      differences were found between growth on cellulose in this study and growth under
      cellobiose-sufficient conditions (E. Guedon, S. Payot, M. Desvaux, and H.
      Petitdemange, Biotechnol. Bioeng. 67:327-335, 2000): (i) while with cellobiose, a
      carbon flow into the cell of as high as 5.14 mmol of hexose equivalent g of
      cells(-1) x h(-1) could be reached, the maximum entering carbon flow obtained
      here on cellulose was 2.91 mmol of hexose equivalent g of cells(-1) x h(-1); (ii)
      while the NADH/NAD+ ratio could reach 1.51 on cellobiose, it was always lower
      than 1 on cellulose; and (iii) while a high proportion of cellobiose was directed
      towards exopolysaccharide, extracellular protein, and free amino acid excretions,
      these overflows were more limited under cellulose-excess conditions. Such
      differences were related to the carbon consumption rate, which was higher on
      cellobiose than on cellulose.

PMID- 11525976
TI  - Flux analysis of the metabolism of Clostridium cellulolyticum grown in cellulose
      fed continuous culture on a chemically defined medium under ammonium-limited
      conditions.
AB  - An investigation of cellulose degradation by the nonruminal, cellulolytic,
      mesophilic bacterium Clostridium cellulolyticum was performed in cellulose-fed
      chemostat cultures with ammonium as the growth-limiting nutrient. At any dilution
      rate (D), acetate was always the main product of the catabolism, with a yield of
      product from substrate ranging between 37.7 and 51.5 g per mol of hexose
      equivalent fermented and an acetate/ethanol ratio always higher than 1. As D
      rose, the acetyl coenzyme A was rerouted in favor of ethanol pathways, and
      ethanol production could represent up to 17.7% of the carbon consumed. Lactate
      was significantly produced, but with increasing D, the specific lactate
      production rate declined, as did the specific rate of production of extracellular
      pyruvate. The proportion of the original carbon directed towards
      phosphoglucomutase remained constant, and the carbon surplus was balanced mainly
      by exopolysaccharide and glycogen biosyntheses at high D values, while
      cellodextrin excretion occurred mainly at lower ones. With increasing D, the
      specific rate of carbon flowing down catabolites increased as well, but when
      expressed as a percentage of carbon it declined, while the percentage of carbon
      directed through biosynthesis pathways was enhanced. The maximum growth and
      energetic yields were lower than those obtained in cellulose-limited chemostats
      and were related to an uncoupling between catabolism and anabolism leading to an
      excess of energy. Compared to growth on cellobiose in ammonium-limited chemostats
      (E. Guedon, M. Desvaux, and H. Petitdemange, J. Bacteriol. 182:2010-2017, 2000),
      (i) a specific consumption rate of carbon of as high as 26.72 mmol of hexose
      equivalent g of cells(-1) x h(-1) could not be reached and (ii) the proportions
      of carbon directed towards cellodextrin, glycogen, and exopolysaccharide pathways
      were not as high as first determined on cellobiose. While the use of cellobiose
      allows highlighting of metabolic limitation and regulation of C. cellulolyticum
      under ammonium-limited conditions, some of these events should then rather be
      interpreted as distortions of the metabolism. Growth of cellulolytic bacteria on
      easily available carbon and nitrogen sources represents conditions far different
      from those of the natural lignocellulosic compounds.

PMID- 11525977
TI  - Control of bacterial motility by environmental factors in polarly flagellated and
      peritrichous bacteria isolated from Lake Baikal.
AB  - Despite numerous studies on bacterial motility, little is known about the
      regulation of this process by environmental factors in natural isolates. In this
      study we investigated the control of bacterial motility in response to
      environmental parameters in two strains isolated from the natural habitat of Lake
      Baikal. Morphological characterization, carbon source utilization, fermentation
      analysis, and sequence comparison of 16S rRNA genes showed that these strains
      belong to two distinct genera, i.e., Enterobacter and Pseudomonas; they were
      named strains 22 and Y1000, respectively. Both strains swarmed at 25 degrees C
      and remained motile at low temperatures (4 degrees C), especially the Pseudomonas
      strain, which further supports the psychrotrophic characteristics of this strain.
      In contrast, a strong inhibition of motility was observed at above 30 degrees C
      and with a high NaCl concentration. The existence of flagellar regulatory
      proteins FlhDC and FleQ was demonstrated in Enterobacter strain 22 and
      Pseudomonas strain Y1000, respectively, and environmental conditions reduced the
      expression of the structural genes potentially located at the first level in the
      flagellar cascade in both organisms. Finally, as in Enterobacter strain 22, a
      strong reduction in the transcription of the master regulatory gene fleQ was
      observed in Pseudomonas strain Y1000 in the presence of novobiocin, a DNA gyrase
      inhibitor, suggesting a link between DNA supercoiling and motility control by
      environmental factors. Thus, striking similarities observed in the two organisms
      suggest that these processes have evolved toward a similar regulatory mechanism
      in polarly flagellated and laterally flagellated (peritrichous) bacteria.

PMID- 11525978
TI  - Construction and environmental release of a Sinorhizobium meliloti strain
      genetically modified to be more competitive for alfalfa nodulation.
AB  - Highly efficient nitrogen-fixing strains selected in the laboratory often fail to
      increase legume production in agricultural soils containing indigenous rhizobial
      populations because they cannot compete against these populations for nodule
      formation. We have previously demonstrated, with a Sinorhizobium meliloti PutA-
      mutant strain, that proline dehydrogenase activity is required for colonization
      and therefore for the nodulation efficiency and competitiveness of S. meliloti on
      alfalfa roots (J. I. Jimenez-Zurdo, P. van Dillewijn, M. J. Soto, M. R. de
      Felipe, J. Olivares, and N. Toro, Mol. Plant-Microbe Interact. 8:492-498, 1995).
      In this work, we investigated whether the putA gene could be used as a means of
      increasing the competitiveness of S. meliloti strains. We produced a construct in
      which a constitutive promoter was placed 190 nucleotides upstream from the start
      codon of the putA gene. This resulted in an increase in the basal expression of
      this gene, with this increase being even greater in the presence of the substrate
      proline. We found that the presence of multicopy plasmids containing this putA
      gene construct increased the competitiveness of S. meliloti in microcosm
      experiments in nonsterile soil planted with alfalfa plants subjected to drought
      stress only during the first month. We investigated whether this construct also
      increased the competitiveness of S. meliloti strains under agricultural
      conditions by using it as the inoculum in a contained field experiment at Leon,
      Spain. We found that the frequency of nodule occupancy was higher with inoculum
      containing the modified putA gene for samples that were analyzed after 34 days
      but not for samples that were analyzed later.

PMID- 11525979
TI  - The viable but nonculturable state of Ralstonia solanacearum may be involved in
      long-term survival and plant infection.
AB  - The role of the dormant-like viable but nonculturable (VBNC) condition in the
      etiology of bacterial infection was examined using a plant system. The plant
      pathogenic bacterium Ralstonia solanacearum was first shown to enter into the
      VBNC state both in response to cupric sulfate when in a saline solution and when
      placed in autoclaved soil. To determine if the VBNC condition is related to
      pathogenesis, the physiological status of bacteria recovered from different
      regions of inoculated tomato plants was determined at different stages of
      infection. The fraction of in planta bacteria that were VBNC increased during
      infection and became greater than 99% by the late stage of disease. The
      possibility that soil-dwelling VBNC bacteria may resuscitate and infect plants
      was also examined. When tomato seeds were germinated in sterile soil that
      contained VBNC but no detectable culturable forms of R. solanacearum cells,
      resuscitation was observed to occur in soil adjacent to plant roots; these
      resuscitated bacteria were able to infect plants. This is the first report of R.
      solanacearum entering the VBNC state and of resuscitation of any VBNC plant
      pathogenic bacteria and provides evidence that the VBNC state may be involved in
      explaining the persistent nature of some infections.

PMID- 11525980
TI  - Putative virulence factor expression by clinical and food isolates of Bacillus
      spp. after growth in reconstituted infant milk formulae.
AB  - Forty-seven strains representing 14 different Bacillus species isolated from
      clinical and food samples were grown in reconstituted infant milk formulae (IMF)
      and subsequently assessed for adherence to, invasion of, and cytotoxicity toward
      HEp-2 and Caco-2 cells. Cell-free supernatant fluids from 38 strains (81%) were
      shown to be cytotoxic, 43 strains (91%) adhered to the test cell lines, and 23
      strains (49%) demonstrated various levels of invasion. Of the 21 Bacillus cereus
      strains examined, 5 (24%) were invasive. A larger percentage of clinically
      derived Bacillus species (20%) than of similar species tested from the food
      environment were invasive. Increased invasion occurred after growth of selected
      Bacillus species in reconstituted IMF containing glucose. While PCR primer
      studies revealed that many different Bacillus species contained DNA sequences
      encoding the hemolysin BL (HBL) enterotoxin complex and B. cereus enterotoxin T,
      not all of these isolates expressed these diarrheagenic genes after growth in
      reconstituted IMF. Of the 47 Bacillus isolates examined, 3 isolates of B. cereus
      and 1 isolate of B. subtilis produced the HBL enterotoxin after 18 h of growth in
      brain heart infusion broth. However, eight isolates belonging to the species B.
      cereus, B. licheniformis, B. circulans, and B. megaterium were found to produce
      this enterotoxin after growth in reconstituted IMF when assessed with the B.
      cereus enterotoxin (diarrheal type) reversed passive latex agglutination (RPLA)
      kit. It is concluded that several Bacillus species occurring occasionally in
      clinical specimens and food samples are of potential medical significance due to
      the expression of putative virulence factors.

PMID- 11525981
TI  - Laboratory evolution of toluene dioxygenase to accept 4-picoline as a substrate.
AB  - We are using directed evolution to extend the range of dioxygenase-catalyzed
      biotransformations to include substrates that are either poorly accepted or not
      accepted at all by the naturally occurring enzymes. Here we report on the
      oxidation of a heterocyclic substrate, 4-picoline, by toluene dioxygenase (TDO)
      and improvement of the enzyme's activity by laboratory evolution. The
      biotransformation of 4-picoline proceeds at only approximately 4.5% of the rate
      of the natural reaction on toluene. Random mutagenesis, saturation mutagenesis,
      and screening directly for product formation using a modified Gibbs assay
      generated mutant TDO 3-B38, in which the wild-type stop codon was replaced with a
      codon encoding threonine. Escherichia coli-expressed TDO 3-B38 exhibited 5.6
      times higher activity toward 4-picoline and approximately 20% more activity
      towards toluene than wild-type TDO. The product of the biotransformation of 4
      picoline is 3-hydroxy-4-picoline; no cis-diols of 4-picoline were observed.

PMID- 11525982
TI  - Self-protection against cell wall hydrolysis in Streptococcus milleri NMSCC 061
      and analysis of the millericin B operon.
AB  - Streptococcus milleri NMSCC 061 produces an endopeptidase, millericin B, which
      hydrolyzes the peptide moiety of susceptible cell wall peptidoglycan. The
      nucleotide sequence of a 4.9-kb chromosomal region showed three open reading
      frames (ORFs) and a putative tRNA(Leu) sequence. The three ORFs encode a
      millericin B preprotein (MilB), a putative immunity protein (MilF), and a
      putative transporter protein (MilT). The milB gene encodes a 277-amino-acid
      preprotein with an 18-amino-acid signal peptide with a consensus IIGG cleavage
      motif. The predicted protein encoded by milT is homologous to ABC (ATP-binding
      cassette) transporters of several bacteriocin systems and to proteins implicated
      in the signal-sequence-independent export of Escherichia coli hemolysin A. These
      similarities strongly suggest that the milT gene product is involved in the
      translocation of millericin B. The gene milF encodes a protein of 302 amino acids
      that shows similarities to the FemA and FemB proteins of Staphylococcus aureus,
      which are involved in the addition of glycine to a pentapeptide peptidoglycan
      precursor. Comparisons of the cell wall mucopeptide of S. milleri NMSCC
      061(resistant to lysis by millericin B) and S. milleri NMSCC 051(sensitive)
      showed a single amino acid difference. Serial growth of S. milleri NMSCC 051 in a
      cell wall minimal medium containing an increased concentration of leucine
      resulted in the in vivo substitution of leucine for threonine in the mucopeptide
      of the cell wall. A cell wall variant of S. milleri NMSCC 051 (sensitive) that
      contained an amino acid substitution (leucine for threonine) within its
      peptidoglycan cross bridge showed partial susceptibility to millericin B. The
      putative tRNA(Leu) sequence located upstream of milB may be a cell wall-specific
      tRNA and could together with the milF protein, play a potential role in the
      addition of leucine to the pentapeptide peptidoglycan precursor and thereby,
      contributing to self-protection to millericin B in the producer strain.

PMID- 11525983
TI  - Combination of competitive quantitative PCR and constant-denaturant capillary
      electrophoresis for high-resolution detection and enumeration of microbial cells.
AB  - A novel quantitative PCR (QPCR) approach, which combines competitive PCR with
      constant-denaturant capillary electrophoresis (CDCE), was adapted for enumerating
      microbial cells in environmental samples using the marine nanoflagellate
      Cafeteria roenbergensis as a model organism. Competitive PCR has been used
      successfully for quantification of DNA in environmental samples. However, this
      technique is labor intensive, and its accuracy is dependent on an internal
      competitor, which must possess the same amplification efficiency as the target
      yet can be easily discriminated from the target DNA. The use of CDCE circumvented
      these problems, as its high resolution permitted the use of an internal
      competitor which differed from the target DNA fragment by a single base and thus
      ensured that both sequences could be amplified with equal efficiency. The
      sensitivity of CDCE also enabled specific and precise detection of sequences over
      a broad range of concentrations. The combined competitive QPCR and CDCE approach
      accurately enumerated C. roenbergensis cells in eutrophic, coastal seawater at
      abundances ranging from approximately 10 to 10(4) cells x ml(-1). The QPCR cell
      estimates were confirmed by fluorescent in situ hybridization counts, but
      estimates of samples with <50 cells x ml(-1) by QPCR were less variable. This
      novel approach extends the usefulness of competitive QPCR by demonstrating its
      ability to reliably enumerate microorganisms at a range of environmentally
      relevant cell concentrations in complex aquatic samples.

PMID- 11525984
TI  - Potential role of fomites in the vehicular transmission of human astroviruses.
AB  - The persistence of human astroviruses dried on representative porous (paper) and
      nonporous (china) surfaces was investigated. Long-term astrovirus survival on
      fomites was monitored by an integrated cell culture-reverse transcription-PCR
      procedure. Viruses were applied to inanimate surfaces in the presence and absence
      of fecal material, and their survival was assayed at 4 and 20 degrees C with high
      relative humidity. Astroviruses exhibited a notable persistence when dried on
      porous and nonporous materials, particularly at low temperature. Short-term
      survival of astroviruses on fomites was compared to that of other enteric viruses
      significant for health, such as rotavirus, adenovirus, poliovirus, and hepatitis
      A virus. Overall, astroviruses persisted better than poliovirus and adenovirus,
      although they exhibited a shorter survival than rotavirus and hepatitis A virus.
      Astroviruses show a high level of persistence at the desiccation step, which is
      of major significance in determining the chance of subsequent virus survival
      dried on fomites. Astroviruses are able to survive on inert surfaces long enough
      to suggest that fomites may play a relevant role in the secondary transmission of
      astrovirus diarrhea.

PMID- 11525985
TI  - Seasonal and spatial variability in Lake Michigan sediment small-subunit rRNA
      concentrations.
AB  - We have used molecular biological methods to study the distribution of microbial
      small-subunit rRNAs (SSU rRNAs), in relation to chemical profiles, in offshore
      Lake Michigan sediments. The sampling site is at a depth of 100 m, with
      temperatures of 2 to 4 degrees C year-round. RNA extracted from sediment was
      probed with radiolabeled oligonucleotides targeting bacterial, archaeal, and
      eukaryotic SSU rRNAs, as well as with a universal probe. The coverage of these
      probes in relation to the present sequence database is discussed. Because
      ribosome production is growth rate regulated, rRNA concentrations are an
      indicator of the microbial populations active in situ. Over a 1-year period,
      changes in sedimentary SSU rRNA concentrations followed seasonal changes in
      surface water temperature and SSU rRNA concentration. Sedimentary depth profiles
      of oxygen, reduced manganese and iron, and sulfate changed relatively little from
      season to season, but the nitrate concentration was approximately fivefold higher
      in April and June 1997 than at the other times sampling was done. We propose that
      sediment microbial SSU rRNA concentrations at our sampling site are influenced by
      seasonal inputs from the water column, particularly the settling of the spring
      diatom bloom, and that the timing of this input may be modulated by grazers, such
      that ammonia becomes available to sediment microbes sooner than fresh organic
      carbon. Nitrate production from ammonia by autotrophic nitrifying bacteria,
      combined with low activity of heterotrophic denitrifying bacteria in the absence
      of readily degradable organic carbon, could account for the cooccurrence of high
      nitrate and low SSU rRNA concentrations.

PMID- 11525986
TI  - Effect of Bacillus thuringiensis Cry1 toxins in insect hemolymph and their
      neurotoxicity in brain cells of Lymantria dispar.
AB  - Little information is available on the systemic effects of Bacillus thuringiensis
      toxins in the hemocoel of insects. In order to test whether B. thuringiensis
      activated toxins elicit a toxic response in the hemocoel, we measured the effect
      of intrahemocoelic injections of several Cry1 toxins on the food intake, growth,
      and survival of Lymantria dispar (Lepidoptera) and Neobellieria bullata (Diptera)
      larvae. Injection of Cry1C was highly toxic to the Lymantria larvae and resulted
      in the complete inhibition of food intake, growth arrest, and death in a dose
      dependent manner. Cry1Aa and Cry1Ab (5 microg/0.2 g [fresh weight] [g fresh wt])
      also affected growth and food intake but were less toxic than Cry1C (0.5
      microg/0.2 g fresh wt). Cry1E and Cry1Ac (5 microg/0.2 g fresh wt) had no toxic
      effect upon injection. Cry1C was also highly toxic to N. bullata larvae upon
      injection. Injection of 5 microg/0.2 g fresh wt resulted in rapid paralysis,
      followed by hemocytic melanization and death. Lower concentrations delayed
      pupariation or gave rise to malformation of the puparium. Finally, Cry1C was
      toxic to brain cells of Lymantria in vitro. The addition of Cry1C (20 microg/ml)
      to primary cultures of Lymantria brain cells resulted in rapid lysis of the
      cultured neurons.

PMID- 11525987
TI  - Examination of recovery in vitro and in vivo of nonculturable Escherichia coli
      O157:H7.
AB  - Escherichia coli O157:H7 (strains ATCC 43895 and FO46) became nonculturable in
      sterile, distilled, deionized water or after exposure to chlorine. Recovery of
      nonculturable E. coli O157:H7 was examined by in vitro and in vivo methods. The
      decline in culturability of starved E. coli O157:H7 was measured by plate count
      on rich medium. Recovery in vitro of nonculturable cells was conducted with media
      amended with catalase or sodium pyruvate; however, there was no apparent increase
      over culturable cell counts on amended versus nonamended media. Although
      nonculturable E. coli O157:H7 did not recover under in vitro conditions, a mouse
      model was used to determine if in vivo conditions would provide sufficient
      conditions for recovery of nonculturable E. coli O157:H7. In separate studies,
      mice were orally challenged with starvation-induced nonculturable cells (FO46) or
      chlorine-induced nonculturable cells (43895 and FO46). Passage through the mouse
      gastrointestinal tract had no effect on recovery of nonculturable (starvation or
      chlorine induced) E. coli O157:H7 (43895 or FO46), based on analysis of fecal
      samples. Mouse kidneys were assayed for the presence of Shiga toxin using the
      Vero cell assay. Differences in cytotoxicity towards Vero cells from kidney
      samples of mice receiving nonculturable cells and control mice were not
      significant, suggesting a loss of virulence.

PMID- 11525988
TI  - Antimicrobial properties of pyridine-2,6-dithiocarboxylic acid, a metal chelator
      produced by Pseudomonas spp.
AB  - Pyridine-2,6-dithiocarboxylic acid (pdtc) is a metal chelator produced by
      Pseudomonas spp. It has been shown to be involved in the biodegradation of carbon
      tetrachloride; however, little is known about its biological function. In this
      study, we examined the antimicrobial properties of pdtc and the mechanism of its
      antibiotic activity. The growth of Pseudomonas stutzeri strain KC, a pdtc
      producing strain, was significantly enhanced by 32 microM pdtc. All
      nonpseudomonads and two strains of P. stutzeri were sensitive to 16 to 32 microM
      pdtc. In general, fluorescent pseudomonads were resistant to all concentrations
      tested. In competition experiments, strain KC demonstrated antagonism toward
      Escherichia coli. This effect was partially alleviated by 100 microM FeCl3. Less
      antagonism was observed in mutant derivatives of strain KC (CTN1 and KC657) which
      lack the ability to produce pdtc. A competitive advantage was restored to strain
      CTN1 by cosmid pT31, which restores pdtc production. pT31 also enhanced the pdtc
      resistance of all pdtc-sensitive strains, indicating that this plasmid contains
      elements responsible for resistance to pdtc. The antimicrobial effect of pdtc was
      reduced by the addition of Fe(III), Co(III), and Cu(II) and enhanced by Zn(II).
      Analyses by mass spectrometry determined that Cu(I):pdtc and Co(III):pdtc2 form
      immediately under our experimental conditions. Our results suggest that pdtc is
      an antagonist and that metal sequestration is the primary mechanism of its
      antimicrobial activity. It is also possible that Zn(II), if present, may play a
      role in pdtc toxicity.

PMID- 11525989
TI  - Isolation of an insertion sequence from Ralstonia solanacearum race 1 and its
      potential use for strain characterization and detection.
AB  - A new insertion sequence (IS), IS1405, was isolated and characterized from a
      Ralstonia solanacearum race 1 strain by the method of insertional inactivation of
      the sacB gene. Sequence analysis indicated that the IS is closely related to the
      members of IS5 family, but the extent of nucleotide sequence identity in 5' and
      3' noncoding regions between IS1405 and other members of IS5 family is only 23 to
      31%. Nucleotide sequences of these regions were used to design specific
      oligonucleotide primers for detection of race 1 strains by PCR. The PCR amplified
      a specific DNA fragment for all R. solanacearum race 1 strains tested, and no
      amplification was observed with some other plant-pathogenic bacteria. Analysis of
      nucleotide sequences flanking IS1405 and additional five endogenous IS1405s that
      reside in the chromosome of R. solanacearum race 1 strains indicated that IS1405
      prefers a target site of CTAR and has two different insertional orientations with
      respect to this target site. Restriction fragment length polymorphism (RFLP)
      pattern analysis using IS1405 as a probe revealed extensive genetic variation
      among strains of R. solanacearum race 1 isolated from eight different host plants
      in Taiwan. The RFLP patterns were then used to subdivide the race 1 strains into
      two groups and several subgroups, which allowed for tracking different subgroup
      strains of R. solanacearum through a host plant community. Furthermore, specific
      insertion sites of IS1405 in certain subgroups were used as a genetic marker to
      develop subgroup-specific primers for detection of R. solanacearum, and thus, the
      subgroup strains can be easily identified through a rapid PCR assay rather than
      RFLP analysis.

PMID- 11525991
TI  - Energy yield of respiration on chloroaromatic compounds in Desulfitobacterium
      dehalogenans.
AB  - The amount of energy that can be conserved via halorespiration by
      Desulfitobacterium dehalogenans JW/IU-DC1 was determined by comparison of the
      growth yields of cells grown with 3-chloro-4-hydroxyphenyl acetate (Cl-OHPA) and
      different electron donors. Cultures that were grown with lactate, pyruvate,
      formate, or hydrogen as an electron donor and Cl-OHPA as an electron acceptor
      yielded 3.1, 6.6, 1.6, and 1.6 g (dry weight) per mol of reduction equivalents,
      respectively. Fermentative growth on pyruvate yielded 14 g (dry weight) per mol
      of pyruvate oxidized. Pyruvate was not fermented stoichiometrically to acetate
      and lactate, but an excess of acetate was produced. Experiments with 13C-labeled
      bicarbonate showed that during pyruvate fermentation, approximately 9% of the
      acetate was formed from the reduction of CO2. Comparison of the growth yields
      suggests that 1 mol of ATP is produced per mol of acetate produced by substrate
      level phosphorylation and that there is no contribution of electron transport
      phosphorylation when D. dehalogenans grows on lactate plus Cl-OHPA or pyruvate
      plus Cl-OHPA. Furthermore, the growth yields indicate that approximately 1/3 mol
      of ATP is conserved per mol of Cl-OHPA reduced in cultures grown in formate plus
      Cl-OHPA and hydrogen plus Cl-OHPA. Because neither formate nor hydrogen nor Cl
      OHPA supports substrate-level phosphorylation, energy must be conserved through
      the establishment of a proton motive force. Pyruvate ferredoxin oxidoreductase,
      lactate dehydrogenase, formate dehydrogenase, and hydrogenase were localized by
      in vitro assays with membrane-impermeable electron acceptors and donors. The
      orientation of chlorophenol-reductive dehalogenase in the cytoplasmic membrane,
      however, could not be determined. A model is proposed, which may explain the
      topology analyses as well as the results obtained in the yield study.

PMID- 11525990
TI  - Prevalence, antigenic specificity, and bactericidal activity of poultry anti
      Campylobacter maternal antibodies.
AB  - Poultry are considered the major reservoir for Campylobacter jejuni, a leading
      bacterial cause of human food-borne diarrhea. To understand the ecology of C.
      jejuni and develop strategies to control C. jejuni infection in the animal
      reservoir, we initiated studies to examine the potential role of anti
      Campylobacter maternal antibodies in protecting young broiler chickens from
      infection by C. jejuni. Using an enzyme-linked immunosorbent assay (ELISA), the
      prevalence of anti-C. jejuni antibodies in breeder chickens, egg yolks, and
      broilers from multiple flocks of different farms were examined. High levels of
      antibodies to the organism were detected in serum samples of breeder chickens and
      in egg yolk contents. To determine the dynamics of anti-Campylobacter maternal
      antibody transferred from yolks to hatchlings, serum samples collected from five
      broiler flocks at weekly intervals from 1 to 28 or 42 days of age were also
      examined by ELISA. Sera from the 1-day and 7-day-old chicks showed high titers of
      antibodies to C. jejuni. Thereafter, antibody titers decreased substantially and
      were not detected during the third and fourth weeks of age. The disappearance of
      anti-Campylobacter maternal antibodies during 3 to 4 weeks of age coincides with
      the appearance of C. jejuni infections observed in many broiler chicken flocks.
      As shown by immunoblotting, the maternally derived antibodies recognized multiple
      membrane proteins of C. jejuni ranging from 19 to 107 kDa. Moreover, in vitro
      serum bactericidal assays showed that anti-Campylobacter maternal antibodies were
      active in antibody-dependent complement-mediated killing of C. jejuni. Together,
      these results highlight the widespread presence of functional anti-Campylobacter
      antibodies in the poultry production system and provide a strong rationale for
      further investigation of the potential role of anti-C. jejuni maternal antibodies
      in protecting young chickens from infection by C. jejuni.

PMID- 11525992
TI  - Effect of turbulent-flow pasteurization on survival of Mycobacterium avium subsp.
      paratuberculosis added to raw milk.
AB  - A pilot-scale pasteurizer operating under validated turbulent flow (Reynolds
      number, 11,050) was used to study the heat sensitivity of Mycobacterium avium
      subsp. paratuberculosis added to raw milk. The ATCC 19698 type strain, ATCC 43015
      (Linda, human isolate), and three bovine isolates were heated in raw whole milk
      for 15 s at 63, 66, 69, and 72 degrees C in duplicate trials. No strains survived
      at 72 degrees C for 15 s; and only one strain survived at 69 degrees C. Means of
      pooled D values (decimal reduction times) at 63 and 66 degrees C were 15.0 +/-
      2.8 s (95% confidence interval) and 5.9 +/- 0.7 s (95% confidence interval),
      respectively. The mean extrapolated D72 degrees C was <2.03 s. This was
      equivalent to a >7 log10 kill at 72 degrees C for 15 s (95% confidence interval).
      The mean Z value (degrees required for the decimal reduction time to traverse one
      log cycle) was 8.6 degrees C. These five strains showed similar survival whether
      recovery was on Herrold's egg yolk medium containing mycobactin or by a
      radiometric culture method (BACTEC). Milk was inoculated with fresh fecal
      material from a high-level fecal shedder with clinical Johne's disease. After
      heating at 72 degrees C for 15 s, the minimum M. avium subsp. paratuberculosis
      kill was >4 log10. Properly maintained and operated equipment should ensure the
      absence of viable M. avium subsp. paratuberculosis in retail milk and other
      pasteurized dairy products. An additional safeguard is the widespread commercial
      practice of pasteurizing 1.5 to 2 degrees above 72 degrees C.

PMID- 11525993
TI  - Direct incorporation of glucosamine and N-acetylglucosamine into exopolymers by
      Gluconacetobacter xylinus (=Acetobacter xylinum) ATCC 10245: production of
      chitosan-cellulose and chitin-cellulose exopolymers.
AB  - Gluconacetobacter xylinus (=Acetobacter xylinum) ATCC 10245 incorporated 2-amino
      2-deoxy-D-glucose (glucosamine) and 2-acetamido-2-deoxy-D-glucose (N
      acetylglucosamine), but not 3-O-methyl-D-glucose or 2-deoxy-D-glucose into
      exopolymers. Incorporation was confirmed by gas chromatography with and without
      mass spectrometry, Fourier transform infrared, and 1H nuclear magnetic resonance.
      The average molar percentage of glucosamine and N-acetylglucosamine in the
      exopolymers was about 18%.

PMID- 11525994
TI  - UDP-N-acetylglucosamine 4-epimerase activity indicates the presence of N
      acetylgalactosamine in exopolysaccharides of Streptococcus thermophilus strains.
AB  - The monomer composition of the exopolysaccharides (EPS) produced by Streptococcus
      thermophilus LY03 and S. thermophilus Sfi20 were evaluated by high-pressure
      liquid chromatography with amperometric detection and nuclear magnetic resonance
      spectroscopy. Both strains produced the same EPS composed of galactose, glucose,
      and N-acetylgalactosamine. Further, it was demonstrated that the activity of the
      precursor-producing enzyme UDP-N-acetylglucosamine 4-epimerase, converting UDP-N
      acetylglucosamine into UDP-N-acetylgalactosamine, is responsible for the presence
      of N-acetylgalactosamine in the EPS repeating units of both strains. The activity
      of UDP-N-acetylglucosamine 4-epimerase was higher in both S. thermophilus strains
      than in a non-EPS-producing control strain. However, the level of this activity
      was not correlated with EPS yields, a result independent of the carbohydrate
      source applied in the fermentation process. On the other hand, both the amounts
      of EPS and the carbohydrate consumption rates were influenced by the type of
      carbohydrate source used during S. thermophilus Sfi20 fermentations. A
      correlation between activities of the enzymes alpha-phosphoglucomutase, UDP
      glucose pyrophosphorylase, and UDP-galactose 4-epimerase and EPS yields was seen.
      These experiments confirm earlier observed results for S. thermophilus LY03,
      although S. thermophilus Sfi20 preferentially consumed glucose for EPS production
      instead of lactose in contrast to the former strain.

PMID- 11525995
TI  - Detection of legionellae in hospital water samples by quantitative real-time
      LightCycler PCR.
AB  - Contamination of hospital water systems with legionellae is a well-known cause of
      nosocomial legionellosis. We describe a new real-time LightCycler PCR assay for
      quantitative determination of legionellae in potable water samples. Primers that
      amplify both a 386-bp fragment of the 16S rRNA gene from Legionella spp. and a
      specifically cloned fragment of the phage lambda, added to each sample as an
      internal inhibitor control, were used. The amplified products were detected by
      use of a dual-color hybridization probe assay design and quantified with external
      standards composed of Legionella pneumophila genomic DNA. The PCR assay had a
      sensitivity of 1 fg of Legionella DNA (i.e., less than one Legionella organism)
      per assay and detected 44 Legionella species and serogroups. Seventy-seven water
      samples from three hospitals were investigated by PCR and culture. The rates of
      detection of legionellae were 98.7% (76 of 77) by the PCR assay and 70.1% (54 of
      77) by culture; PCR inhibitors were detected in one sample. The amounts of
      legionellae calculated from the PCR results were associated with the CFU detected
      by culture (r = 0.57; P < 0.001), but PCR results were mostly higher than the
      culture results. Since L. pneumophila is the main cause of legionellosis, we
      further developed a quantitative L. pneumophila-specific PCR assay targeting the
      macrophage infectivity potentiator (mip) gene, which codes for an immunophilin of
      the FK506 binding protein family. All but one of the 16S rRNA gene PCR-positive
      water samples were also positive in the mip gene PCR, and the results of the two
      PCR assays were correlated. In conclusion, the newly developed Legionella genus
      specific and L. pneumophila species-specific PCR assays proved to be valuable
      tools for investigation of Legionella contamination in potable water systems.

PMID- 11525996
TI  - Cosecretion of chaperones and low-molecular-size medium additives increases the
      yield of recombinant disulfide-bridged proteins.
AB  - Attempts were made to engineer the periplasm of Escherichia coli to an expression
      compartment of heterologous proteins in their native conformation. As a first
      approach the low-molecular-size additive L-arginine and the redox compound
      glutathione (GSH) were added to the culture medium. Addition of 0.4 M L-arginine
      and 5 mM reduced GSH increased the yield of a native tissue-type plasminogen
      activator variant (rPA), consisting of the kringle-2 and the protease domain, and
      a single-chain antibody fragment (scFv) up to 10- and 37-fold, respectively. A
      variety of other medium additives also had positive effects on the yield of rPA.
      In a second set of experiments, the effects of cosecreted ATP-independent
      molecular chaperones on the yields of native therapeutic proteins were
      investigated. At optimized conditions, cosecretion of E. coli DnaJ or murine
      Hsp25 increased the yield of native rPA by a factor of 170 and 125, respectively.
      Cosecretion of DnaJ also dramatically increased the amount of a second model
      protein, native proinsulin, in the periplasm. The results of this study are
      anticipated to initiate a series of new approaches to increase the yields of
      native, disulfide-bridged, recombinant proteins in the periplasm of E. coli.

PMID- 11525997
TI  - Identification and characterization of a chitinase antigen from Pseudomonas
      aeruginosa strain 385.
AB  - A chitinase antigen has been identified in Pseudomonas aeruginosa strain 385
      using sera from animals immunized with a whole-cell vaccine. The majority of the
      activity was shown to be in the cytoplasm, with some activity in the membrane
      fraction. The chitinase was not secreted into the culture medium. Purification of
      the enzyme was achieved by exploiting its binding to crab shell chitin. The
      purified enzyme had a molecular mass of 58 kDa by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis and a pI of 5.2. NH2-terminal amino acid
      sequencing revealed two sequences of M(I/L)RID and (Q/M/V)AREDAAAAM that gave an
      exact match to sequences in a translated putative open reading frame from the P.
      aeruginosa genome. The chitinase was active against chitin azure, ethylene glycol
      chitin, and colloidal chitin. It did not display any lysozyme activity. Using
      synthetic 4-methylumbelliferyl chitin substrates, it was shown to be an
      endochitinase. The Km and kcat for 4-nitrophenyl-beta-D-N,N'-diacetylchitobiose
      were 4.28 mM and 1.7 s(-1) respectively, and for 4-nitrophenyl-beta-D-N,N',N"
      triacetylchitotriose, they were 0.48 mM and 0.16 s(-1) respectively. The pH
      optimum was determined to be pH 6.75, and 90% activity was maintained over the pH
      range 6.5 to 7.1. The enzyme was stable over the pH range 5 to 10 for 3 h and to
      temperatures up to 50 degrees C for 30 min. The chitinase bound strongly to
      chitin, chitin azure, colloidal chitin, lichenan, and cellulose but poorly to
      chitosan, xylan, and heparin. It is suggested that the chitinase functions
      primarily as a chitobiosidase, removing chitobiose from the nonreducing ends of
      chitin and chitin oligosaccharides.

PMID- 11525998
TI  - nifH sequences and nitrogen fixation in type I and type II methanotrophs.
AB  - Some methane-oxidizing bacteria (methanotrophs) are known to be capable of
      expressing nitrogenase and utilizing N2 as a nitrogen source. However, no
      sequences are available for nif genes in these strains, and the known nitrogen
      fixing methanotrophs are confined mainly to a few genera. The purpose of this
      work was to assess the nitrogen-fixing capabilities of a variety of methanotroph
      strains. nifH gene fragments from four type I methanotrophs and seven type II
      methanotrophs were PCR amplified and sequenced. Nitrogenase activity was
      confirmed in selected type I and type II strains by acetylene reduction.
      Activities ranged from 0.4 to 3.3 nmol/min/mg of protein. Sequence analysis shows
      that the nifH sequences from the type I and type II strains cluster with nifH
      sequences from other gamma proteobacteria and alpha proteobacteria, respectively.
      The translated nifH sequences from three Methylomonas strains show high identity
      (95 to 99%) to several published translated environmental nifH sequences PCR
      amplified from rice roots and a freshwater lake. The translated nifH sequences
      from the type II strains show high identity (94 to 99%) to published translated
      nifH sequences from a variety of environments, including rice roots, a freshwater
      lake, an oligotrophic ocean, and forest soil. These results provide evidence for
      nitrogen fixation in a broad range of methanotrophs and suggest that nitrogen
      fixing methanotrophs may be widespread and important in the nitrogen cycling of
      many environments.

PMID- 11525999
TI  - Obligate sulfide-dependent degradation of methoxylated aromatic compounds and
      formation of methanethiol and dimethyl sulfide by a freshwater sediment isolate,
      Parasporobacterium paucivorans gen. nov., sp. nov.
AB  - Methanethiol (MT) and dimethyl sulfide (DMS) have been shown to be the dominant
      volatile organic sulfur compounds in freshwater sediments. Previous research
      demonstrated that in these habitats MT and DMS are derived mainly from the
      methylation of sulfide. In order to identify the microorganisms that are
      responsible for this type of MT and DMS formation, several sulfide-rich
      freshwater sediments were amended with two potential methyl group-donating
      compounds, syringate and 3,4,5-trimethoxybenzoate (0.5 mM). The addition of these
      methoxylated aromatic compounds resulted in excess accumulation of MT and DMS in
      all sediment slurries even though methanogenic consumption of MT and DMS
      occurred. From one of the sediment slurries tested, a novel anaerobic bacterium
      was isolated with syringate as the sole carbon source. The strain, designated
      Parasporobacterium paucivorans, produced MT and DMS from the methoxy groups of
      syringate. The hydroxylated aromatic residue (gallate) was converted to acetate
      and butyrate. Like Sporobacterium olearium, another methoxylated aromatic
      compound-degrading bacterium, the isolate is a member of the XIVa cluster of the
      low-GC-content Clostridiales group. However, the new isolate differs from all
      other known methoxylated aromatic compound-degrading bacteria because it was able
      to degrade syringate in significant amounts only in the presence of sulfide.

PMID- 11526000
TI  - Enzymatic manganese(II) oxidation by a marine alpha-proteobacterium.
AB  - A yellow-pigmented marine bacterium, designated strain SD-21, was isolated from
      surface sediments of San Diego Bay, San Diego, Calif., based on its ability to
      oxidize soluble Mn(II) to insoluble Mn(III, IV) oxides. 16S rRNA analysis
      revealed that this organism was most closely related to members of the genus
      Erythrobacter, aerobic anoxygenic phototrophic bacteria within the alpha-4
      subgroup of the Proteobacteria (alpha-4 Proteobacteria). SD-21, however, has a
      number of distinguishing phenotypic features relative to Erythrobacter species,
      including the ability to oxidize Mn(II). During the logarithmic phase of growth,
      this organism produces Mn(II)-oxidizing factors of approximately 250 and 150 kDa
      that are heat labile and inhibited by both azide and o-phenanthroline, suggesting
      the involvement of a metalloenzyme. Although the expression of the Mn(II) oxidase
      was not dependent on the presence of Mn(II), higher overall growth yields were
      reached in cultures incubated with Mn(II) in the culture medium. In addition, the
      rate of Mn(II) oxidation appeared to be slower in cultures grown in the light.
      This is the first report of Mn(II) oxidation within the alpha-4 Proteobacteria as
      well as the first Mn(II)-oxidizing proteins identified in a marine gram-negative
      bacterium.

PMID- 11526001
TI  - Toxic effects of Ag(I) and Hg(II) on Candida albicans and C. maltosa: a flow
      cytometric evaluation.
AB  - The effects of Ag(I) and Hg(II) on membrane potential and integrity of cells of
      Candida albicans and C. maltosa were determined with a flow cytometric procedure
      that employed an anionic membrane potential-sensitive dye, bis-(1,3
      dibutylbarbituric acid) trimethine oxonol, and a membrane integrity indicator,
      propidium iodide. The membrane potentials of cells of both species were reduced
      rapidly within 15 min of exposure to Ag(I). No threshold dose for Hg(II) existed,
      and cells of both species lost membrane potential gradually in Hg(II) solutions.
      Cells of both species lost membrane integrity more rapidly in Ag(I) solutions
      than in Hg(II) solutions. In Ag(I) solutions, the decrease in the numbers of
      cells recoverable in culture occurred at a rate similar to the rate of cell
      depolarization and membrane permeabilization. In Hg(II) solutions, loss of cell
      recoverability preceded the loss of membrane potential and membrane integrity. C.
      albicans, in contrast to C. maltosa, showed no loss of membrane integrity after
      exposure to Hg(II) solutions for 1 h. Different rates of binding of Ag(I) and
      Hg(II) between the two species suggest that the two ions target different primary
      sites.

PMID- 11526002
TI  - Survival of fecal coliforms in dry-composting toilets.
AB  - The dry-composting toilet, which uses neither water nor sewage infrastructure, is
      a practical solution in areas with inadequate sewage disposal and where water is
      limited. These systems are becoming increasingly popular and are promoted to
      sanitize human excreta and to recycle them into fertilizer for nonedible plants,
      yet there are few data on the safety of this technology. This study analyzed
      fecal coliform reduction in approximately 90 prefabricated, dry-composting
      toilets (Sistema Integral de Reciclamiento de Desechos Organicos [SIRDOs]) that
      were installed on the U.S.-Mexico border in Ciudad Juarez, Chihuahua, Mexico. The
      purpose of this study was to determine fecal coliform reduction over time and the
      most probable method of this reduction. Biosolid waste samples were collected and
      analyzed at approximately 3 and 6 months and were classified based on U.S.
      Environmental Protection Agency standards. Results showed that class A compost
      (high grade) was present in only 35.8% of SIRDOs after 6 months. The primary
      mechanism for fecal coliform reduction was found to be desiccation rather than
      biodegradation. There was a significant correlation (P = 0.008) between
      classification rating and percent moisture categories of the biosolid samples:
      drier samples had a greater proportion of class A samples. Solar exposure was
      critical for maximal class A biosolid end products (P = 0.001). This study only
      addressed fecal coliforms as an indicator organism, and further research is
      necessary to determine the safety of composting toilets with respect to other
      pathogenic microorganisms, some of which are more resistant to desiccation.

PMID- 11526003
TI  - Identification of a new plasmid-encoded sec-dependent bacteriocin produced by
      Listeria innocua 743.
AB  - Listeria innocua 743 produces an inhibitory activity demonstrating broad-spectrum
      inhibition of Listeria monocytogenes isolates. Gel-electrophoretic analysis of
      culture supernatants indicated that two inhibitors with different molecular
      weights were produced by this strain. Insertion of Tn917 into a 2.9 Kb plasmid
      (pHC743) generated mutants with either an impaired ability or a loss in ability
      to produce one of the inhibitors. Sequence analysis of the transposon insertion
      regions revealed the presence of two continuous open reading frames, the first
      encoding a new pediocin-like bacteriocin (lisA) and the second encoding a protein
      homologous with genes involved in immunity toward other bacteriocins (lisB).
      Translation of the bacteriocin gene (lisA) initiates from a noncanonical start
      codon and encodes a 71-amino-acid prebacteriocin which lacked the double glycine
      leader peptidase processing site common in other type II bacteriocins. Alignment
      of the sequence with the processed N termini of related bacteriocins suggests
      that the mature bacteriocin consists of 43 amino acids, with a predicted
      molecular mass of 4,484 Da. Mutants containing insertions into lisA were
      sensitive to the inhibitor, indicating that lisAB forms a single operon and that
      lisB represents the immunity protein. Cloning of an amplicon containing the lisAB
      operon into Escherichia coli resulted in expression and export of the
      bacteriocin. This finding confirms that the phenotype is dependent on the
      structural and immunity gene only and that export of this bacteriocin is sec
      dependent. This is the first confirmation of bacteriocin production in a Listeria
      spp., and it is of interest that this bacteriocin is closely related to the
      pediocin family of bacteriocins produced by lactic acid bacteria.

PMID- 11526004
TI  - Salmonella enterica serovar Typhimurium DT104 displays a rugose phenotype.
AB  - Rugose phenotypes, such as those observed in Vibrio cholerae, have increased
      resistance to chlorine, oxidative stress, and complement-mediated killing. In
      this study we identified and defined a rugose phenotype in Salmonella enterica
      serovar Typhimurium DT104 and showed induction only on certain media at 25
      degrees C after 3 days of incubation. Incubation at 37 degrees C resulted in the
      appearance of the smooth phenotype. Observation of the ultrastructure of the
      rugose form and a stable smooth variant (Stv), which was isolated following a
      series of passages of the rugose cells, revealed extracellular substances only in
      cells from the rugose colony. Observation of the extracellular substance by
      scanning electron microscopy (SEM) was correlated with the appearance of
      corrugation during development of rugose colony morphology over a 4-day
      incubation period at 25 degrees C. In addition, the cells also formed a pellicle
      in liquid broth, which was associated with the appearance of interlacing slime
      and fibrillar structures, as observed by SEM. The pellicle-forming cells were
      completely surrounded by capsular material, which bound cationic ferritin, thus
      indicating the presence of an extracellular anionic component. The rugose cells,
      in contrast to Stv, showed resistance to low pH and hydrogen peroxide and an
      ability to form biofilms. Based on these results and analogy to the rugose
      phenotype in V. cholerae, we propose a possible role for the rugose phenotype in
      the survival of S. enterica serovar Typhimurium DT104.

PMID- 11526005
TI  - Transformation of chlorinated benzenes and toluenes by Ralstonia sp. strain PS12
      tecA (tetrachlorobenzene dioxygenase) and tecB (chlorobenzene dihydrodiol
      dehydrogenase) gene products.
AB  - The tecB gene, located downstream of tecA and encoding tetrachlorobenzene
      dioxygenase, in Ralstonia sp. strain PS12 was cloned into Escherichia coli
      DH5alpha together with the tecA gene. The identity of the tecB gene product as a
      chlorobenzene dihydrodiol dehydrogenase was verified by transformation into the
      respective catechols of chlorobenzene, the three isomeric dichlorobenzenes, as
      well as 1,2,3- and 1,2,4-trichlorobenzenes, all of which are transformed by TecA
      into the respective dihydrodihydroxy derivatives. Di- and trichlorotoluenes were
      either subject to TecA-mediated dioxygenation (the major or sole reaction
      observed for the 1,2,4-substituted 2,4-, 2,5-, and 3,4-dichlorotoluenes),
      resulting in the formation of the dihydrodihydroxy derivatives, or to
      monooxygenation of the methyl substituent (the major or sole reaction observed
      for 2,3-, 2,6-, and 3,5-dichloro- and 2,4,5-trichlorotoluenes), resulting in
      formation of the respective benzyl alcohols. All of the chlorotoluenes subject to
      dioxygenation by TecA were transformed, without intermediate accumulation of
      dihydrodihydroxy derivatives, into the respective catechols by TecAB, indicating
      that dehydrogenation is no bottleneck for chlorobenzene or chlorotoluene
      degradation. However, only those chlorotoluenes subject to a predominant
      dioxygenation were growth substrates for PS12, confirming that monooxygenation is
      an unproductive pathway in PS12.

PMID- 11526006
TI  - Low-temperature lipase from psychrotrophic Pseudomonas sp. strain KB700A.
AB  - We have previously reported that a psychrotrophic bacterium, Pseudomonas sp.
      strain KB700A, which displays sigmoidal growth even at -5 degrees C, produced a
      lipase. A genomic DNA library of strain KB700A was introduced into Escherichia
      coli TG1, and screening on tributyrin-containing agar plates led to the isolation
      of the lipase gene. Sequence analysis revealed an open reading frame (KB-lip)
      consisting of 1,422 nucleotides that encoded a protein (KB-Lip) of 474 amino
      acids with a molecular mass of 49,924 Da. KB-Lip showed 90% identity with the
      lipase from Pseudomonas fluorescens and was found to be a member of Subfamily I.3
      lipase. Gene expression and purification of the recombinant protein were
      performed. KB-Lip displayed high lipase activity in the presence of Ca2+.
      Addition of EDTA completely abolished lipase activity, indicating that KB-Lip was
      a Ca2+-dependent lipase. Addition of Mn2+ and Sr2+ also led to enhancement of
      lipase activity but to a much lower extent than that produced by Ca2+. The
      optimal pH of KB-Lip was 8 to 8.5. The addition of detergents enhanced the enzyme
      activity. When p-nitrophenyl esters and triglyceride substrates of various chain
      lengths were examined, the lipase displayed highest activity towards C10 acyl
      groups. We also determined the positional specificity and found that the activity
      was 20-fold higher toward the 1(3) position than toward the 2 position. The
      optimal temperature for KB-Lip was 35 degrees C, lower than that for any
      previously reported Subfamily I.3 lipase. The enzyme was also thermolabile
      compared to these lipases. Furthermore, KB-Lip displayed higher levels of
      activity at low temperatures than did other enzymes from Subfamily I.3,
      indicating that KB-Lip has evolved to function in cold environments, in
      accordance with the temperature range for growth of its psychrotrophic host,
      strain KB700A.

PMID- 11526007
TI  - Rapid identification and differentiation of the soft rot erwinias by 16S-23S
      intergenic transcribed spacer-PCR and restriction fragment length polymorphism
      analyses.
AB  - Current identification methods for the soft rot erwinias are both imprecise and
      time-consuming. We have used the 16S-23S rRNA intergenic transcribed spacer (ITS)
      to aid in their identification. Analysis by ITS-PCR and ITS-restriction fragment
      length polymorphism was found to be a simple, precise, and rapid method compared
      to current molecular and phenotypic techniques. The ITS was amplified from
      Erwinia and other genera using universal PCR primers. After PCR, the banding
      patterns generated allowed the soft rot erwinias to be differentiated from all
      other Erwinia and non-Erwinia species and placed into one of three groups (I to
      III). Group I comprised all Erwinia carotovora subsp. atroseptica and subsp.
      betavasculorum isolates. Group II comprised all E. carotovora subsp. carotovora,
      subsp. odorifera, and subsp. wasabiae and E. cacticida isolates, and group III
      comprised all E. chrysanthemi isolates. To increase the level of discrimination
      further, the ITS-PCR products were digested with one of two restriction enzymes.
      Digestion with CfoI identified E. carotovora subsp. atroseptica and subsp.
      betavasculorum (group I) and E. chrysanthemi (group III) isolates, while
      digestion with RsaI identified E. carotovora subsp. wasabiae, subsp. carotovora,
      and subsp. odorifera/carotovora and E. cacticida isolates (group II). In the
      latter case, it was necessary to distinguish E. carotovora subsp. odorifera and
      subsp. carotovora using the alpha-methyl glucoside test. Sixty suspected soft rot
      erwinia isolates from Australia were identified as E. carotovora subsp.
      atroseptica, E. chrysanthemi, E. carotovora subsp. carotovora, and non-soft rot
      species. Ten "atypical" E. carotovora subsp. atroseptica isolates were identified
      as E. carotovora subsp. atroseptica, subsp. carotovora, and subsp. betavasculorum
      and non-soft rot species, and two "atypical" E. carotovora subsp. carotovora
      isolates were identified as E. carotovora subsp. carotovora and subsp.
      atroseptica.

PMID- 11526008
TI  - Growth patterns of two marine isolates: adaptations to substrate patchiness?
AB  - During bottle incubations of heterotrophic marine picoplankton, some bacterial
      groups are conspicuously favored. In an earlier investigation bacteria of the
      genus Pseudoalteromonas rapidly multiplied in substrate-amended North Sea water,
      whereas the densities of Oceanospirillum changed little (H. Eilers, J.
      Pernthaler, and R. Amann, Appl. Environ. Microbiol. 66:4634-4640, 2000). We
      therefore studied the growth patterns of two isolates affiliating with
      Pseudoalteromonas and Oceanospirillum in batch culture. Upon substrate resupply,
      Oceanospirillum lagged threefold longer than Pseudoalteromonas but reached more
      than fivefold-higher final cell density and biomass. A second, mobile morphotype
      was present in the starved Oceanospirillum populations with distinctly greater
      cell size, DNA and protein content, and 16S rRNA concentration. Contrasting
      cellular ribosome concentrations during stationary phase suggested basic
      differences in the growth responses of the two strains to a patchy environment.
      Therefore, we exposed the strains to different modes of substrate addition.
      During cocultivation on a single batch of substrates, the final cell densities of
      Oceanospirillum were reduced three times as much as those Pseudoalteromonas,
      compared to growth yields in pure cultures. In contrast, the gradual addition of
      substrates to stationary-phase cocultures was clearly disadvantageous for the
      Pseudoalteromonas population. Different growth responses to substrate gradients
      could thus be another facet affecting the competition between marine bacteria and
      may help to explain community shifts observed during enrichments.

PMID- 11526009
TI  - Heteroduplex panel analysis, a novel method for genetic identification of
      Aspergillus Section Flavi strains.
AB  - For genetic identification of Aspergillus Section Flavi isolates and detection of
      intraspecific variation, we developed a novel method for heteroduplex panel
      analysis (HPA) utilizing fragments of the internal transcribed spacer (ITS)
      regions (ITS1-5.8S-ITS2) of the rRNA gene that was PCR amplified with universal
      primers. The method involves formation of heteroduplexes with a set of reference
      fragments amplified from Aspergillus flavus, A. parasiticus, A. tamarii, and A.
      nomius and subsequent minislab vinyl polymer gel electrophoresis. The test panel
      is compared with species-specific standard panels (F-1, P-1, T-1, and N-1)
      generated by pairwise reannealing among four reference fragments. Of 90 test
      panels, 89 succeeded in identifying the species and 74 were identical to one of
      the four standard panels. Of the 16 new panels, 11 A. flavus/A. oryzae panels
      were identical and typed as F-2 and 4 of 5 A. nomius panels were typed as N-2 or
      N-3. The other strain, A. nomius IMI 358749, was unable to identify the species
      because no single bands were formed with any of the four reference strains. DNA
      sequencing revealed that our HPA method has the highest sensitivity available and
      is able to detect as little as one nucleotide of diversity within the species.
      When Penicillium or non-Section Flavi Aspergillus was subjected to HPA, the
      resulting bands of heteroduplexes showed apparently lower mobility and poor
      heteroduplex formation. This indicates that HPA is a useful identification method
      without morphological observation and is suitable for rapid and inexpensive
      screening of large numbers of isolates. The HPA typing coincided with the
      taxonomy of Section Flavi and is therefore applicable as an alternative to the
      conventional methods (Samson, R. A., E. S. Hoekstra, J. C. Frisvad, and O.
      Filtenborg, p. 64-97, in Introduction to Food- and Airborne Fungi, 6th ed.,
      2000).

PMID- 11526010
TI  - Differentiation of strains of Xylella fastidiosa by a variable number of tandem
      repeat analysis.
AB  - Short sequence repeats (SSRs) with a potential variable number of tandem repeat
      (VNTR) loci were identified in the genome of the citrus pathogen Xylella
      fastidiosa and used for typing studies. Although mono- and dinucleotide repeats
      were absent, we found several intermediate-length 7-, 8-, and 9-nucleotide
      repeats, which we examined for allelic polymorphisms using PCR. Five genuine VNTR
      loci were highly polymorphic within a set of 27 X. fastidiosa strains from
      different hosts. The highest average Nei's measure of genetic diversity (H)
      estimated for VNTR loci was 0.51, compared to 0.17 derived from randomly
      amplified polymorphic DNA (RAPD) analysis. For citrus X. fastidiosa strains, some
      specific VNTR loci had a H value of 0.83, while the maximum value given by
      specific RAPD loci was 0.12. Our approach using VNTR markers provides a high
      resolution tool for epidemiological, genetic, and ecological analysis of citrus
      specific X. fastidiosa strains.

PMID- 11526011
TI  - Characterization of the single superoxide dismutase of Staphylococcus xylosus.
AB  - Staphylococcus xylosus is a facultative anaerobic bacterium used as a starter
      culture for fermented meat products. In an attempt to analyze the antioxidant
      capacities of this organism, the superoxide dismutase (SOD) was characterized. S.
      xylosus contains a single cytoplasmic SOD, which was not inhibited by H2O2. The
      SOD activity in crude extracts was completely lost upon metal depletion, but it
      could be recovered by manganese and very weakly by iron. It is therefore
      suggested that the S. xylosus SOD is a manganese-preferring enzyme. The
      corresponding gene, sod, was isolated from a genomic library of S. xylosus DNA
      and complemented the growth defect of an Escherichia coli SOD-deficient mutant.
      As deduced from the nucleotide sequence, sod encodes a protein of 199 amino acids
      with a molecular mass of 22.5 kDa. Two transcriptional start sites 25 and 120 bp
      upstream of the sod start codon were identified. A terminator-like structure
      downstream of the gene suggested a monocistronic sod mRNA. Regulation of sod
      expression was studied using fusions of the sod promoters to a genomic
      promoterless beta-galactosidase gene. The sod expression was not affected by
      manganese and increased slightly with paraquat. It was induced during stationary
      phase in a complex medium but not in a chemically defined medium. To investigate
      the physiological role of SOD, a mutant devoid of SOD activity was constructed.
      Growth experiments showed that sod is not essential for aerobic growth in complex
      medium. However, in chemically defined medium without leucine, isoleucine, and
      valine, the sod mutant hardly grew, in contrast to the wild-type strain. In
      addition, the mutant was sensitive to hyperbaric oxygen and to paraquat.
      Therefore, sod plays an important role in the protection of S. xylosus from
      oxidative stress.

PMID- 11526012
TI  - gly gene cloning and expression and purification of glycinecin A, a bacteriocin
      produced by Xanthomonas campestris pv. glycines 8ra.
AB  - Glycinecin A, a bacteriocin produced by Xanthomonas campestris pv. glycines,
      inhibits the growth of X. campestris pv. vesicatoria. We have cloned and
      expressed the genes encoding glycinecin A in Escherichia coli. Recombinant
      glycinecin A was purified from cell extracts by ammonium sulfate precipitation
      followed by chromatography on Q-Sepharose, Mono Q (ion exchange), and size
      exclusion columns. Purified glycinecin A is composed of two polypeptides, is
      active over a wide pH range (6 to 9), and is stable at temperatures up to 60
      degrees C. Glycinecin A is a heterodimer consisting of 39- and 14-kDa subunits,
      as revealed through size exclusion chromatography and cross-linking analysis. Two
      genes, glyA and glyB, encoding the 39- and 14-kDa subunits, respectively, were
      identified based on the N-terminal sequences of the subunits. From the nucleotide
      sequences of glyA and glyB, we conclude that both genes are translated as
      bacteriocin precursors that include N-terminal leader sequences. When expressed
      in E. coli, recombinant glycinecin A was found primarily in cell extracts. In
      contrast, most glycinecin A from Xanthomonas was found in the culture media. E.
      coli transformed with either glyA or glyB separately did not show the bacteriocin
      activity.

PMID- 11526013
TI  - Ruminococcin A, a new lantibiotic produced by a Ruminococcus gnavus strain
      isolated from human feces.
AB  - When cultivated in the presence of trypsin, the Ruminococcus gnavus E1 strain,
      isolated from a human fecal sample, was able to produce an antibacterial
      substance that accumulated in the supernatant. This substance, called
      ruminococcin A, was purified to homogeneity by reverse-phase chromatography. It
      was shown to be a 2,675-Da bacteriocin harboring a lanthionine structure. The
      utilization of Edman degradation and tandem mass spectrometry techniques,
      followed by DNA sequencing of part of the structural gene, allowed the
      identification of 21 amino acid residues. Similarity to other bacteriocins
      present in sequence libraries strongly suggested that ruminococcin A belonged to
      class IIA of the lantibiotics. The purified ruminococcin A was active against
      various pathogenic clostridia and bacteria phylogenetically related to R. gnavus.
      This is the first report on the characterization of a bacteriocin produced by a
      strictly anaerobic bacterium from human fecal microbiota.

PMID- 11526015
TI  - Effect of challenge temperature and solute type on heat tolerance of Salmonella
      serovars at low water activity.
AB  - Salmonella spp. are reported to have an increased heat tolerance at low water
      activity (a(w); measured by relative vapor pressure [rvp]), achieved either by
      drying or by incorporating solutes. Much of the published data, however, cover
      only a narrow treatment range and have been analyzed by assuming first-order
      death kinetics. In this study, the death of Salmonella enterica serovar
      Typhimurium DT104 when exposed to 54 combinations of temperature (55 to 80
      degrees C) and a(w) (rvp 0.65 to 0.90, reduced using glucose-fructose) was
      investigated. The Weibull model (LogS = -bt(n)) was used to describe microbial
      inactivation, and surface response models were developed to predict death rates
      for serovar Typhimurium at all points within the design surface. The models were
      evaluated with data generated by using six different Salmonella strains in place
      of serovar Typhimurium DT104 strain 30, two different solutes in place of glucose
      fructose to reduce a(w), or six low-a(w) foods artificially contaminated with
      Salmonella in place of the sugar broths. The data demonstrate that, at
      temperatures of > or =70 degrees C, Salmonella cells at low a(w) were more heat
      tolerant than those at a higher a(w) but below 65 degrees C the reverse was true.
      The same patterns were generated when sucrose (rvp 0.80 compared with 0.90) or
      NaCl (0.75 compared with 0.90) was used to reduce a(w), but the extent of the
      protection afforded varied with solute type. The predictions of thermal death
      rates in the low-a(w) foods were usually fail-safe, but the few exceptions
      highlight the importance of validating models with specific foods that may have
      additional factors affecting survival.

PMID- 11526014
TI  - Signal peptide and propeptide optimization for heterologous protein secretion in
      Lactococcus lactis.
AB  - Lactic acid bacteria are food-grade microorganisms that are potentially good
      candidates for production of heterologous proteins of therapeutical or
      technological interest. We developed a model for heterologous protein secretion
      in Lactococcus lactis using the staphylococcal nuclease (Nuc). The effects on
      protein secretion of alterations in either (i) signal peptide or (ii) propeptide
      sequences were examined. (i) Replacement of the native Nuc signal peptide
      (SP(Nuc)) by that of L. lactis protein Usp45 (SP(Usp)) resulted in greatly
      improved secretion efficiency (SE). Pulse-chase experiments showed that Nuc
      secretion kinetics was better when directed by SP(Usp) than when directed by
      SP(Nuc). This SP(Usp) effect on Nuc secretion is not due to a better antifolding
      activity, since SP(Usp):Nuc precursor proteins display enzymatic activity in
      vitro, while SP(Nuc):Nuc precursor proteins do not. (ii) Deletion of the native
      Nuc propeptide dramatically reduces Nuc SE, regardless of which SP is used. We
      previously reported that a synthetic propeptide, LEISSTCDA, could efficiently
      replace the native Nuc propeptide to promote heterologous protein secretion in L.
      lactis (Y. Le Loir, A. Gruss, S. D. Ehrlich, and P. Langella, J. Bacteriol.
      180:1895-1903, 1998). To determine whether the LEISSTCDA effect is due to its
      acidic residues, specific substitutions were introduced, resulting in neutral or
      basic propeptides. Effects of these two new propeptides and of a different acidic
      synthetic propeptide were tested. Acidic and neutral propeptides were equally
      effective in enhancing Nuc SE and also increased Nuc yields. In contrast, the
      basic propeptide strongly reduced both SE and the quantity of secreted Nuc. We
      have shown that the combination of the native SP(Usp) and a neutral or acidic
      synthetic propeptide leads to a significant improvement in SE and in the quantity
      of synthesized Nuc. These observations will be valuable in the production of
      heterologous proteins in L. lactis.

PMID- 11526016
TI  - Survival of Lactobacillus delbrueckii subsp. bulgaricus and Streptococcus
      thermophilus in the terminal ileum of fistulated Gottingen minipigs.
AB  - The ability of Lactobacillus delbrueckii subsp. bulgaricus and Streptococcus
      thermophilus administered in yogurt to survive the passage through the upper
      gastrointestinal tract was investigated with Gottingen minipigs that were fitted
      with ileum T-cannulas. After ingestion of yogurt containing viable
      microorganisms, ileostomy samples were collected nearly every hour beginning 3 h
      after food uptake. Living L. delbrueckii subsp. bulgaricus and S. thermophilus
      were detected in the magnitude of 10(6) to 10(7) per gram of intestinal contents
      (wet weight) in all animals under investigation. A calculation of the minimum
      amount of surviving bacteria that had been administered is presented. Total DNA
      extracted from ileostomy samples was subjected to PCR, which was species specific
      for L. delbrueckii and S. thermophilus and subspecies specific for L. delbrueckii
      subsp. bulgaricus. All three bacterial groups could be detected by PCR after
      yogurt uptake but not after uptake of a semisynthetic diet. One pig apparently
      had developed an endogenous L. delbrueckii flora. When heat-treated yogurt was
      administered, L. delbrueckii was detected in all animals. S. thermophilus or L.
      delbrueckii subsp. bulgaricus was not detected, indicating that heat-inactivated
      cells and their DNAs had already been digested and their own L. delbrueckii flora
      had been stimulated for growth.

PMID- 11526017
TI  - Characterization of Schizosaccharomyces pombe malate permease by expression in
      Saccharomyces cerevisiae.
AB  - In Saccharomyces cerevisiae, L-malic acid transport is not carrier mediated and
      is limited to slow, simple diffusion of the undissociated acid. Expression in S.
      cerevisiae of the MAE1 gene, encoding Schizosaccharomyces pombe malate permease,
      markedly increased L-malic acid uptake in this yeast. In this strain, at pH 3.5
      (encountered in industrial processes), L-malic acid uptake involves Mae1p
      mediated transport of the monoanionic form of the acid (apparent kinetic
      parameters: Vmax = 8.7 nmol/mg/min; Km = 1.6 mM) and some simple diffusion of the
      undissociated L-malic acid (Kd = 0.057 min(-1)). As total L-malic acid transport
      involved only low levels of diffusion, the Mae1p permease was further
      characterized in the recombinant strain. L-Malic acid transport was reversible
      and accumulative and depended on both the transmembrane gradient of the
      monoanionic acid form and the DeltapH component of the proton motive force.
      Dicarboxylic acids with stearic occupation closely related to L-malic acid, such
      as maleic, oxaloacetic, malonic, succinic and fumaric acids, inhibited L-malic
      acid uptake, suggesting that these compounds use the same carrier. We found that
      increasing external pH directly inhibited malate uptake, resulting in a lower
      initial rate of uptake and a lower level of substrate accumulation. In S. pombe,
      proton movements, as shown by internal acidification, accompanied malate uptake,
      consistent with the proton/dicarboxylate mechanism previously proposed.
      Surprisingly, no proton fluxes were observed during Mae1p-mediated L-malic acid
      import in S. cerevisiae, and intracellular pH remained constant. This suggests
      that, in S. cerevisiae, either there is a proton counterflow or the Mae1p
      permease functions differently from a proton/dicarboxylate symport.

PMID- 11526018
TI  - Rapid and efficient extraction method for reverse transcription-PCR detection of
      hepatitis A and Norwalk-like viruses in shellfish.
AB  - As part of an effort to develop a broadly applicable test for Norwalk-like
      viruses and hepatitis A virus (HAV) in shellfish, a rapid extraction method that
      is suitable for use with one-step reverse transcription (RT)-PCR-based detection
      methods was developed. The method involves virus extraction using a pH 9.5
      glycine buffer, polyethylene glycol (PEG) precipitation, Tri-reagent, and
      purification of viral poly(A) RNA by using magnetic poly(dT) beads. This glycine
      PEG-Tri-reagent-poly(dT) method can be performed in less than 8 h on hard-shell
      clams (Mercenaria mercenaria) and Eastern oysters (Crassostrea virginica) and,
      when coupled with RT-PCR-based detection, can yield results within 24 h. Observed
      sensitivities for seeded shellfish extracts are as low as 0.015 PFU of HAV and
      22.4 RT-PCR50 units for Norwalk virus. Detection of HAV in live oysters
      experimentally exposed to contaminated seawater is also demonstrated. An
      adaptation of this method was used to identify HAV in imported clams (tentatively
      identified as Ruditapes philippinarum) implicated in an outbreak of food-borne
      viral illness. All of the required reagents are commercially available. This
      method should facilitate the implementation of RT-PCR testing of commercial
      shellfish.

PMID- 11526019
TI  - Novel ring cleavage products in the biotransformation of biphenyl by the yeast
      Trichosporon mucoides.
AB  - The yeast Trichosporon mucoides, grown on either glucose or phenol, was able to
      transform biphenyl into a variety of mono-, di-, and trihydroxylated derivatives
      hydroxylated on one or both aromatic rings. While some of these products
      accumulated in the supernatant as dead end products, the ortho-substituted
      dihydroxylated biphenyls were substrates for further oxidation and ring fission.
      These ring fission products were identified by high-performance liquid
      chromatography, gas chromatography-mass spectrometry, and nuclear magnetic
      resonance analyses as phenyl derivatives of hydroxymuconic acids and the
      corresponding pyrones. Seven novel products out of eight resulted from the
      oxidation and ring fission of 3,4-dihydroxybiphenyl. Using this compound as a
      substrate, 2-hydroxy-4-phenylmuconic acid, (5-oxo-3-phenyl-2,5-dihydrofuran-2
      yl)acetic acid, and 3-phenyl-2-pyrone-6-carboxylic acid were identified. Ring
      cleavage of 3,4,4'-trihydroxybiphenyl resulted in the formation of [5-oxo-3-(4'
      hydroxyphenyl)-2,5-dihydrofuran-2-yl]acetic acid, 4-(4'-hydroxyphenyl)-2-pyrone-6
      carboxylic acid, and 3-(4'-hydroxyphenyl)-2-pyrone-6-carboxylic acid. 2,3,4
      trihydroxybiphenyl was oxidized to 2-hydroxy-5-phenylmuconic acid, and 4-phenyl-2
      pyrone-6-carboxylic acid was the transformation product of 3,4,5
      trihydroxybiphenyl. All these ring fission products were considerably less toxic
      than the hydroxylated derivatives.

PMID- 11526020
TI  - Role of an essential acyl coenzyme A carboxylase in the primary and secondary
      metabolism of Streptomyces coelicolor A3(2).
AB  - Two genes, accB and accE, that form part of the same operon, were cloned from
      Streptomyces coelicolor A3(2). AccB is homologous to the carboxyl transferase
      domain of several propionyl coezyme A (CoA) carboxylases and acyl-CoA
      carboxylases (ACCases) of actinomycete origin, while AccE shows no significant
      homology to any known protein. Expression of accB and accE in Escherichia coli
      and subsequent in vitro reconstitution of enzyme activity in the presence of the
      biotinylated protein AccA1 or AccA2 confirmed that AccB was the carboxyl
      transferase subunit of an ACCase. The additional presence of AccE considerably
      enhanced the activity of the enzyme complex, suggesting that this small
      polypeptide is a functional component of the ACCase. The impossibility of
      obtaining an accB null mutant and the thiostrepton growth dependency of a tipAp
      accB conditional mutant confirmed that AccB is essential for S. coelicolor
      viability. Normal growth phenotype in the absence of the inducer was restored in
      the conditional mutant by the addition of exogenous long-chain fatty acids in the
      medium, indicating that the inducer-dependent phenotype was specifically related
      to a conditional block in fatty acid biosynthesis. Thus, AccB, together with
      AccA2, which is also an essential protein (E. Rodriguez and H. Gramajo,
      Microbiology 143:3109-3119, 1999), are the most likely components of an ACCase
      whose main physiological role is the synthesis of malonyl-CoA, the first
      committed step of fatty acid synthesis. Although normal growth of the conditional
      mutant was restored by fatty acids, the cultures did not produce actinorhodin or
      undecylprodigiosin, suggesting a direct participation of this enzyme complex in
      the supply of malonyl-CoA for the synthesis of these secondary metabolites.

PMID- 11526021
TI  - Detection of methanotroph diversity on roots of submerged rice plants by
      molecular retrieval of pmoA, mmoX, mxaF, and 16S rRNA and ribosomal DNA,
      including pmoA-based terminal restriction fragment length polymorphism profiling.
AB  - The diversity of methanotrophic bacteria associated with roots of submerged rice
      plants was assessed using cultivation-independent techniques. The research
      focused mainly on the retrieval of pmoA, which encodes the alpha subunit of the
      particulate methane monooxygenase. A novel methanotroph-specific community
      profiling method was established using the terminal restriction fragment length
      polymorphism (T-RFLP) technique. The T-RFLP profiles clearly revealed a more
      complex root-associated methanotrophic community than did banding patterns
      obtained by pmoA-based denaturing gradient gel electrophoresis. The comparison of
      pmoA-based T-RFLP profiles obtained from rice roots and bulk soil of flooded rice
      microcosms suggested that there was a substantially higher abundance of type I
      methanotrophs on rice roots than in the bulk soil. These were affiliated to the
      genera Methylomonas, Methylobacter, Methylococcus, and to a novel type I
      methanotroph sublineage. By contrast, type II methanotrophs of the Methylocystis
      Methylosinus group could be detected with high relative signal intensity in both
      soil and root compartments. Phylogenetic treeing analyses and a set of substrate
      diagnostic amino acid residues provided evidence that a novel pmoA lineage was
      detected. This branched distinctly from all currently known methanotrophs. To
      examine whether the retrieval of pmoA provided a complete view of root-associated
      methanotroph diversity, we also assessed the diversity detectable by recovery of
      genes coding for subunits of soluble methane monooxygenase (mmoX) and methanol
      dehydrogenase (mxaF). In addition, both 16S rRNA and 16S ribosomal DNA (rDNA)
      were retrieved using a PCR primer set specific to type I methanotrophs. The
      overall methanotroph diversity detected by recovery of mmoX, mxaF, and 16S rRNA
      and 16S rDNA corresponded well to the diversity detectable by retrieval of pmoA.

PMID- 11526022
TI  - Survival of clinical and poultry-derived isolates of Campylobacter jejuni at a
      low temperature (4 degrees C).
AB  - Campylobacter jejuni is a leading cause of bacterial gastroenteritis in humans,
      and contamination of poultry has been implicated in illness. The bacteria are
      fastidious in terms of their temperature requirements, being unable to grow below
      ca. 31 degrees C, but have been found to be physiologically active at lower
      temperatures and to tolerate exposure to low temperatures in a strain-dependent
      manner. In this study, 19 field isolates of C. jejuni (10 of clinical and 9 of
      poultry origin) were studied for their ability to tolerate prolonged exposure to
      low temperature (4 degrees C). Although substantial variability was found among
      different strains, clinical isolates tended to be significantly more likely to
      remain viable following cold exposure than poultry-derived strains. In contrast,
      the relative degree of tolerance of the bacteria to freezing at -20 degrees C and
      freeze-thawing was strain specific but independent of strain source (poultry
      versus clinical) and degree of cold (4 degrees C) tolerance.

PMID- 11526023
TI  - Production of recombinant alpha-galactosidases in Thermus thermophilus.
AB  - A Thermus thermophilus selector strain for production of thermostable and
      thermoactive alpha-galactosidase was constructed. For this purpose, the native
      alpha-galactosidase gene (agaT) of T. thermophilus TH125 was inactivated to
      prevent background activity. In our first attempt, insertional mutagenesis of
      agaT by using a cassette carrying a kanamycin resistance gene led to bacterial
      inability to utilize melibiose (alpha-galactoside) and galactose as sole
      carbohydrate sources due to a polar effect of the insertional inactivation. A
      Gal(+) phenotype was assumed to be essential for growth on melibiose. In a Gal(-)
      background, accumulation of galactose or its metabolite derivatives produced from
      melibiose hydrolysis could interfere with the growth of the host strain harboring
      recombinant alpha-galactosidase. Moreover, the AgaT(-) strain had to be Km(s) for
      establishment of the plasmids containing alpha-galactosidase genes and the
      kanamycin resistance marker. Therefore, a suitable selector strain (AgaT(-)
      Gal(+) Km(s)) was generated by applying integration mutagenesis in combination
      with phenotypic selection. To produce heterologous alpha-galactosidase in T.
      thermophilus, the isogenes agaA and agaB of Bacillus stearothermophilus KVE36
      were cloned into an Escherichia coli-Thermus shuttle vector. The region
      containing the E. coli plasmid sequence (pUC-derived vector) was deleted before
      transformation of T. thermophilus with the recombinant plasmids. As a result,
      transformation efficiency and plasmid stability were improved. However, growth on
      minimal agar medium containing melibiose was achieved only following random
      selection of the clones carrying a plasmid-based mutation that had promoted a
      higher copy number and greater stability of the plasmid.

PMID- 11526024
TI  - Fate of Mycobacterium avium subsp. paratuberculosis in Swiss hard and semihard
      cheese manufactured from raw milk.
AB  - Raw milk was artificially contaminated with declumped cells of Mycobacterium
      avium subsp. paratuberculosis at a concentration of 10(4) to 10(5) CFU/ml and was
      used to manufacture model hard (Swiss Emmentaler) and semihard (Swiss Tisliter)
      cheese. Two different strains of M. avium subsp. paratuberculosis were tested,
      and for each strain, two model hard and semihard cheeses were produced. The
      survival of M. avium subsp. paratuberculosis cells was monitored over a ripening
      period of 120 days by plating out homogenized cheese samples onto 7H10-PANTA
      agar. In both the hard and the semihard cheeses, counts decreased steadily but
      slowly during cheese ripening. Nevertheless, viable cells could still be detected
      in 120-day cheese. D values were calculated at 27.8 days for hard and 45.5 days
      for semihard cheese. The most important factors responsible for the death of M.
      avium subsp. paratuberculosis in cheese were the temperatures applied during
      cheese manufacture and the low pH at the early stages of cheese ripening. Since
      the ripening period for these raw milk cheeses lasts at least 90 to 120 days, the
      D values found indicate that 10(3) to 10(4) cells of M. avium subsp.
      paratuberculosis per g will be inactivated.

PMID- 11526025
TI  - DNA from uncultured organisms as a source of 2,5-diketo-D-gluconic acid
      reductases.
AB  - Total DNA of a population of uncultured organisms was extracted from soil
      samples, and by using PCR methods, the genes encoding two different 2,5-diketo-D
      gluconic acid reductases (DKGRs) were recovered. Degenerate PCR primers based on
      published sequence information gave internal gene fragments homologous to known
      DKGRs. Nested primers specific for the internal fragments were combined with
      random primers to amplify flanking gene fragments from the environmental DNA, and
      two hypothetical full-length genes were predicted from the combined sequences.
      Based on these predictions, specific primers were used to amplify the two
      complete genes in single PCRs. These genes were cloned and expressed in
      Escherichia coli. The purified gene products catalyzed the reduction of 2,5
      diketo-D-gluconic acid to 2-keto-L-gulonic acid. Compared to previously described
      DKGRs isolated from Corynebacterium spp., these environmental reductases
      possessed some valuable properties. Both exhibited greater than 20-fold-higher
      kcat/Km values than those previously determined, primarily as a result of better
      binding of substrate. The Km values for the two new reductases were 57 and 67
      microM, versus 2 and 13 mM for the Corynebacterium enzymes. Both environmental
      DKGRs accepted NADH as well as NADPH as a cosubstrate; other DKGRs and most
      related aldo-keto reductases use only NADPH. In addition, one of the new
      reductases was more thermostable than known DKGRs.

PMID- 11526026
TI  - Microbial population structures in soil particle size fractions of a long-term
      fertilizer field experiment.
AB  - Soil structure depends on the association between mineral soil particles (sand,
      silt, and clay) and organic matter, in which aggregates of different size and
      stability are formed. Although the chemistry of organic materials, total
      microbial biomass, and different enzyme activities in different soil particle
      size fractions have been well studied, little information is available on the
      structure of microbial populations in microhabitats. In this study, topsoil
      samples of different fertilizer treatments of a long-term field experiment were
      analyzed. Size fractions of 200 to 63 microm (fine sand fraction), 63 to 2 microm
      (silt fraction), and 2 to 0.1 microm (clay fraction) were obtained by a
      combination of low-energy sonication, wet sieving, and repeated centrifugation.
      Terminal restriction fragment length polymorphism analysis and cloning and
      sequencing of 16S rRNA genes were used to compare bacterial community structures
      in different particle size fractions. The microbial community structure was
      significantly affected by particle size, yielding higher diversity of microbes in
      small size fractions than in coarse size fractions. The higher biomass previously
      found in silt and clay fractions could be attributed to higher diversity rather
      than to better colonization of particular species. Low nutrient availability,
      protozoan grazing, and competition with fungal organisms may have been
      responsible for reduced diversities in larger size fractions. Furthermore, larger
      particle sizes were dominated by alpha-Proteobacteria, whereas high abundance and
      diversity of bacteria belonging to the Holophaga/Acidobacterium division were
      found in smaller size fractions. Although very contrasting organic amendments
      (green manure, animal manure, sewage sludge, and peat) were examined, our results
      demonstrated that the bacterial community structure was affected to a greater
      extent by the particle size fraction than by the kind of fertilizer applied.
      Therefore, our results demonstrate specific microbe-particle associations that
      are affected to only a small extent by external factors.

PMID- 11526027
TI  - Photoreactivation in airborne Mycobacterium parafortuitum.
AB  - Photoreactivation was observed in airborne Mycobacterium parafortuitum exposed
      concurrently to UV radiation (254 nm) and visible light. Photoreactivation rates
      of airborne cells increased with increasing relative humidity (RH) and decreased
      with increasing UV dose. Under a constant UV dose with visible light absent, the
      UV inactivation rate of airborne M. parafortuitum cells decreased by a factor of
      4 as RH increased from 40 to 95%; however, under identical conditions with
      visible light present, the UV inactivation rate of airborne cells decreased only
      by a factor of 2. When irradiated in the absence of visible light, cellular
      cyclobutane thymine dimer content of UV-irradiated airborne M. parafortuitum and
      Serratia marcescens increased in response to RH increases. Results suggest that,
      unlike in waterborne bacteria, cyclobutane thymine dimers are not the most
      significant form of UV-induced DNA damage incurred by airborne bacteria and that
      the distribution of DNA photoproducts incorporated into UV-irradiated airborne
      cells is a function of RH.

PMID- 11526028
TI  - Bacteriophage latent-period evolution as a response to resource availability.
AB  - Bacteriophages (phages) modify microbial communities by lysing hosts,
      transferring genetic material, and effecting lysogenic conversion. To understand
      how natural communities are affected it is important to develop predictive
      models. Here we consider how variation between models--in eclipse period, latent
      period, adsorption constant, burst size, the handling of differences in host
      quantity and host quality, and in modeling strategy--can affect predictions.
      First we compare two published models of phage growth, which differ primarily in
      terms of how they model the kinetics of phage adsorption; one is a computer
      simulation and the other is an explicit calculation. At higher host quantities
      (approximately 10(8) cells/ml), both models closely predict experimentally
      determined phage population growth rates. At lower host quantities (10(7)
      cells/ml), the computer simulation continues to closely predict phage growth
      rates, but the explicit model does not. Next we concentrate on predictions of
      latent-period optima. A latent-period optimum is the latent period that maximizes
      the population growth of a specific phage growing in the presence of a specific
      quantity and quality of host cells. Both models predict similar latent-period
      optima at higher host densities (e.g., 17 min at 10(8) cells/ml). At lower host
      densities, however, the computer simulation predicts latent-period optima that
      are much shorter than those suggested by explicit calculations (e.g., 90 versus
      1,250 min at 10(5) cells/ml). Finally, we consider the impact of host quality on
      phage latent-period evolution. By taking care to differentiate latent-period
      phenotypic plasticity from latent-period evolution, we argue that the impact of
      host quality on phage latent-period evolution may be relatively small.

PMID- 11526029
TI  - Phylogenetic diversity analysis of subterranean hot springs in Iceland.
AB  - Geothermal energy has been harnessed and used for domestic heating in Iceland. In
      wells that are typically drilled to a depth of 1,500 to 2,000 m, the temperature
      of the source water is 50 to 130 degrees C. The bottoms of the boreholes can
      therefore be regarded as subterranean hot springs and provide a unique
      opportunity to study the subterranean biosphere. Large volumes of geothermal
      fluid from five wells and a mixture of geothermal water from 50 geothermal wells
      (hot tap water) were sampled and concentrated through a 0.2-microm-pore-size
      filter. Cells were observed in wells RG-39 (91.4 degrees C) and MG-18 (71.8
      degrees C) and in hot tap water (76 degrees C), but no cells were detected in
      wells SN-4, SN-5 (95 to 117 degrees C), and RV-5 (130 degrees C). Archaea and
      Bacteria were detected by whole-cell fluorescent in situ hybridization. DNAs were
      extracted from the biomass, and small-subunit rRNA genes (16S rDNAs) were
      amplified by PCR using primers specific for the Archaea and Bacteria domains. The
      PCR products were cloned and sequenced. The sequence analysis showed 11 new
      operational taxonomic units (OTUs) out of 14, 3 of which were affiliated with
      known surface OTUs. Samples from RG-39 and hot tap water were inoculated into
      enrichment media and incubated at 65 and 85 degrees C. Growth was observed only
      in media based on geothermal water. 16S rDNA analysis showed enrichments
      dominated with Desulfurococcales relatives. Two strains belonging to
      Desulfurococcus mobilis and to the Thermus/Deinococcus group were isolated from
      borehole RG-39. The results indicate that subsurface volcanic zones are an
      environment that provides a rich subsurface for novel thermophiles.

PMID- 11526030
TI  - Xylulokinase overexpression in two strains of Saccharomyces cerevisiae also
      expressing xylose reductase and xylitol dehydrogenase and its effect on
      fermentation of xylose and lignocellulosic hydrolysate.
AB  - Fermentation of the pentose sugar xylose to ethanol in lignocellulosic biomass
      would make bioethanol production economically more competitive. Saccharomyces
      cerevisiae, an efficient ethanol producer, can utilize xylose only when
      expressing the heterologous genes XYL1 (xylose reductase) and XYL2 (xylitol
      dehydrogenase). Xylose reductase and xylitol dehydrogenase convert xylose to its
      isomer xylulose. The gene XKS1 encodes the xylulose-phosphorylating enzyme
      xylulokinase. In this study, we determined the effect of XKS1 overexpression on
      two different S. cerevisiae host strains, H158 and CEN.PK, also expressing XYL1
      and XYL2. H158 has been previously used as a host strain for the construction of
      recombinant xylose-utilizing S. cerevisiae strains. CEN.PK is a new strain
      specifically developed to serve as a host strain for the development of metabolic
      engineering strategies. Fermentation was carried out in defined and complex media
      containing a hexose and pentose sugar mixture or a birch wood lignocellulosic
      hydrolysate. XKS1 overexpression increased the ethanol yield by a factor of 2 and
      reduced the xylitol yield by 70 to 100% and the final acetate concentrations by
      50 to 100%. However, XKS1 overexpression reduced the total xylose consumption by
      half for CEN.PK and to as little as one-fifth for H158. Yeast extract and peptone
      partly restored sugar consumption in hydrolysate medium. CEN.PK consumed more
      xylose but produced more xylitol than H158 and thus gave lower ethanol yields on
      consumed xylose. The results demonstrate that strain background and modulation of
      XKS1 expression are important for generating an efficient xylose-fermenting
      recombinant strain of S. cerevisiae.

PMID- 11526031
TI  - Molecular and biochemical analysis of two beta-galactosidases from
      Bifidobacterium infantis HL96.
AB  - Two genes encoding beta-galactosidase isoenzymes, beta-galI and beta-galIII, from
      Bifidobacterium infantis HL96 were revealed on 3.6- and 2.4-kb DNA fragments,
      respectively, by nucleotide sequence analysis of the two fragments. beta-galI
      (3,069 bp) encodes a 1,022-amino-acid (aa) polypeptide with a predicted molecular
      mass of 113 kDa. A putative ribosome binding site and a promoter sequence were
      recognized at the 5' flanking region of beta-galI. Further upstream a partial
      sequence of an open reading frame revealed a putative lactose permease gene
      transcribing divergently from beta-galI. The beta-galIII gene (2,076 bp) encodes
      a 691-aa polypeptide with a calculated molecular mass of 76 kDa. A rho
      independent transcription terminator-like sequence was found 25 bp downstream of
      the termination codon. The amino acid sequences of beta-GalI and beta-GalIII are
      homologous to those found in the LacZ and the LacG families, respectively. The
      acid-base, nucleophilic, and substrate recognition sites conserved in the LacZ
      family were found in beta-GalI, and a possible acid-base site proposed for the
      LacG family was located in beta-GalIII, which featured a glutamate at residue
      160. The coding regions of the beta-galI and beta-galIII genes were each cloned
      downstream of a T7 promoter for overexpression in Escherichia coli. The molecular
      masses of the overexpressed proteins, as estimated by polyacrylamide gel
      electrophoresis on sodium dodecyl sulfate-polyacrylamide gels, agree with their
      predicted molecular weights. beta-GalI and beta-GalIII were specific for beta-D
      anomer-linked galactoside substrates. Both are more active in response to ONPG (o
      nitrophenyl-beta-D-galactopyranoside) than in response to lactose, particularly
      beta-GalIII. The galacto-oligosaccharide yield in the reaction catalyzed by beta
      GalI at 37 degrees C in 20% (wt/vol) lactose solution was 130 mg/ml, which is
      more than six times higher than the maximum yield obtained with beta-GalIII. The
      structure of the major trisaccharide produced by beta-GalI catalysis was
      characterized as O-beta-D-galactopyranosyl-(1-3)-O-beta-D-galactopyranosyl-(1-4)
      D-glucopyranose (3'-galactosyl-lactose).

PMID- 11526032
TI  - Fluorescent method for monitoring cheese starter permeabilization and lysis.
AB  - A fluorescence method to monitor lysis of cheese starter bacteria using dual
      staining with the LIVE/DEAD BacLight bacterial viability kit is described. This
      kit combines membrane-permeant green fluorescent nucleic acid dye SYTO 9 and
      membrane-impermeant red fluorescent nucleic acid dye propidium iodide (PI),
      staining damaged membrane cells fluorescent red and intact cells fluorescent
      green. For evaluation of the fluorescence method, cells of Lactococcus lactis
      MG1363 were incubated under different conditions and subsequently labeled with
      SYTO 9 and PI and analyzed by flow cytometry and epifluorescence microscopy.
      Lysis was induced by treatment with cell wall-hydrolyzing enzyme mutanolysin.
      Cheese conditions were mimicked by incubating cells in a buffer with high
      protein, potassium, and magnesium, which stabilizes the cells. Under
      nonstabilizing conditions a high concentration of mutanolysin caused complete
      disruption of the cells. This resulted in a decrease in the total number of cells
      and release of cytoplasmic enzyme lactate dehydrogenase. In the stabilizing
      buffer, mutanolysin caused membrane damage as well but the cells disintegrated at
      a much lower rate. Stabilizing buffer supported permeabilized cells, as indicated
      by a high number of PI-labeled cells. In addition, permeable cells did not
      release intracellular aminopeptidase N, but increased enzyme activity was
      observed with the externally added and nonpermeable peptide substrate lysyl-p
      nitroanilide. Finally, with these stains and confocal scanning laser microscopy
      the permeabilization of starter cells in cheese could be analyzed.

PMID- 11526033
TI  - cumA multicopper oxidase genes from diverse Mn(II)-oxidizing and non-Mn(II)
      oxidizing Pseudomonas strains.
AB  - A multicopper oxidase gene, cumA, required for Mn(II) oxidation was recently
      identified in Pseudomonas putida strain GB-1. In the present study, degenerate
      primers based on the putative copper-binding regions of the cumA gene product
      were used to PCR amplify cumA gene sequences from a variety of Pseudomonas
      strains, including both Mn(II)-oxidizing and non-Mn(II)-oxidizing strains. The
      presence of highly conserved cumA gene sequences in several apparently non-Mn(II)
      oxidizing Pseudomonas strains suggests that this gene may not be expressed, may
      not be sufficient alone to confer the ability to oxidize Mn(II), or may have an
      alternative function in these organisms. Phylogenetic analysis of both CumA and
      16S rRNA sequences revealed similar topologies between the respective trees,
      including the presence of several distinct phylogenetic clusters. Overall, our
      results indicate that both the cumA gene and the capacity to oxidize Mn(II) occur
      in phylogenetically diverse Pseudomonas strains.

PMID- 11526034
TI  - Improved properties of baker's yeast mutants resistant to 2-deoxy-D-glucose.
AB  - We isolated spontaneous mutants from Saccharomyces cerevisiae (baker's yeast V1)
      that were resistant to 2-deoxy-D-glucose and had improved fermentative capacity
      on sweet doughs. Three mutants could grow at the same rate as the wild type in
      minimal SD medium (0.17% Difco yeast nitrogen base without amino acids and
      ammonium sulfate, 0.5% ammonium sulfate, 2% glucose) and had stable elevated
      levels of maltase and/or invertase under repression conditions but lower levels
      in maltose-supplemented media. Two of the mutants also had high levels of
      phosphatase active on 2-deoxy-D-glucose-6-phosphate. Dough fermentation (CO2
      liberation) by two of the mutants was faster and/or produced higher final volumes
      than that by the wild type, both under laboratory and industrial conditions, when
      the doughs were supplemented with glucose or sucrose. However, the three mutants
      were slower when fermenting plain doughs. Fermented sweet bakery products
      obtained with these mutants were of better quality than those produced by the
      wild type, with regard to their texture and their organoleptic properties.

PMID- 11526035
TI  - Interception of small particles by flocculent structures, sessile ciliates, and
      the basic layer of a wastewater biofilm.
AB  - We investigated attachment processes of hydrophobic and hydrophilic particles
      (diameter = 1 microm) to mature biofilms grown on clay marbles in a sequencing
      batch biofilm reactor. During a treatment cycle with filtered wastewater
      containing different fluorescent beads, the progression of particle density in
      various biofilm compartments (carrier biofilm, basic biofilm layer, biofilm
      flocs, and sessile ciliates) was determined by flow cytometry, confocal laser
      scanning microscopy and automated image analysis. Particles were almost
      completely removed from wastewater by typical processes of particle retention: up
      to 58% of particles attached to clay marbles, up to 15% were associated with
      suspended flocs, and up to 10% were ingested by sessile ciliates. Ingestion of
      particles by ciliates was exceptionally high immediately after wastewater
      addition (1,200 particles grazer(-1) x h(-1)) and continued until approximately
      14% of the water had been cleared by ciliate filter feeding. Most probably,
      ciliate bioturbation increases particle sorption to the basic biofilm.
      Backwashing of the reactor detached pieces of biofilm and thus released
      approximately 50% of the particles into rinsing water. Clay marbles in the upper
      part of the reactor were more efficiently abraded than in the lower part. No
      indications for selective attachment of the applied hydrophobic and hydrophilic
      beads were found. As a consequence of interception patterns, organisms at
      elevated biofilm structures are probably major profiteers of wastewater
      particles; among them, ciliates may be of major importance because of their
      highly active digestive food vacuoles.

PMID- 11526036
TI  - Isolation of toxigenic Nocardiopsis strains from indoor environments and
      description of two new Nocardiopsis Species, N. exhalans sp. nov. and N.
      umidischolae sp. nov.
AB  - Nocardiopsis strains were isolated from water-damaged indoor environments. Two
      strains (N. alba subsp. alba 704a and a strain representing a novel species,
      ES10.1) as well as strains of N. prasina, N. lucentensis, and N. tropica produced
      methanol-soluble toxins that paralyzed the motility of boar spermatozoa at <30
      microg of crude extract (dry weight) x ml(-1). N. prasina, N. lucentensis, N.
      tropica, and strain ES10.1 caused cessation of motility by dissipating the
      mitochondrial membrane potential, Deltapsi, of the boar spermatozoa. Indoor
      strain 704a produced a substance that destroyed cell membrane barrier function
      and depleted the sperm cells of ATP. Indoor strain 64/93 was antagonistic towards
      Corynebacterium renale. Two indoor Nocardiopsis strains were xerotolerant, and
      all five utilized a wide range of substrates. This combined with the production
      of toxic substances suggests good survival and potential hazard to human health
      in water-damaged indoor environments. Two new species, Nocardiopsis exhalans sp.
      nov. (ES10.1T) and Nocardiopsis umidischolae sp. nov. (66/93T), are proposed
      based on morphology, chemotaxonomic and physiological characters, phylogenetic
      analysis, and DNA-DNA reassociations.

PMID- 11526037
TI  - A second quorum-sensing system regulates cell surface properties but not
      phenazine antibiotic production in Pseudomonas aureofaciens.
AB  - The root-associated biological control bacterium Pseudomonas aureofaciens 30-84
      produces a range of exoproducts, including protease and phenazines. Phenazine
      antibiotic biosynthesis by phzXYFABCD is regulated in part by the PhzR-PhzI
      quorum-sensing system. Mutants defective in phzR or phzI produce very low levels
      of phenazines but wild-type levels of exoprotease. In the present study, a second
      genomic region of strain 30-84 was identified that, when present in trans,
      increased beta-galactosidase activity in a genomic phzB::lacZ reporter and
      partially restored phenazine production to a phzR mutant. Sequence analysis
      identified two adjacent genes, csaR and csaI, that encode members of the LuxR
      LuxI family of regulatory proteins. No putative promoter region is present
      upstream of the csaI start codon and no lux box-like element was found in either
      the csaR promoter or the 30-bp intergenic region between csaR and csaI. Both the
      PhzR-PhzI and CsaR-CsaI systems are regulated by the GacS-GacA two-component
      regulatory system. In contrast to the multicopy effects of csaR and csaI in
      trans, a genomic csaR mutant (30-84R2) and a csaI mutant (30-84I2) did not
      exhibit altered phenazine production in vitro or in situ, indicating that the
      CsaR-CsaI system is not involved in phenazine regulation in strain 30-84. Both
      mutants also produced wild-type levels of protease. However, disruption of both
      csaI and phzI or both csaR and phzR eliminated both phenazine and protease
      production completely. Thus, the two quorum-sensing systems do not interact for
      phenazine regulation but do interact for protease regulation. Additionally, the
      CsaI N-acylhomoserine lactone (AHL) signal was not recognized by the phenazine
      AHL reporter 30-84I/Z but was recognized by the AHL reporters Chromobacterium
      violaceum CV026 and Agrobacterium tumefaciens A136(pCF240). Inactivation of csaR
      resulted in a smooth mucoid colony phenotype and formation of cell aggregates in
      broth, suggesting that CsaR is involved in regulating biosynthesis of cell
      surface components. Strain 30-84I/I2 exhibited mucoid colony and clumping
      phenotypes similar to those of 30-84R2. Both phenotypes were reversed by
      complementation with csaR-csaI or by the addition of the CsaI AHL signal. Both
      quorum-sensing systems play a role in colonization by strain 30-84. Whereas loss
      of PhzR resulted in a 6.6-fold decrease in colonization by strain 30-84 on wheat
      roots in natural soil, a phzR csaR double mutant resulted in a 47-fold decrease.
      These data suggest that gene(s) regulated by the CsaR-CsaI system also plays a
      role in the rhizosphere competence of P. aureofaciens 30-84.

PMID- 11526038
TI  - Characterization by 16S rRNA sequence analysis of pseudomonads causing blotch
      disease of cultivated Agaricus bisporus.
AB  - Bacterial blotch of Agaricus bisporus has typically been identified as being
      caused by either Pseudomonas tolaasii (brown blotch) or Pseudomonas gingeri
      (ginger blotch). To address the relatedness of pseudomonads able to induce
      blotch, a pilot study was initiated in which pseudomonads were selectively
      isolated from mushroom farms throughout New Zealand. Thirty-three pseudomonad
      isolates were identified as being capable of causing different degrees of
      discoloration (separable into nine categories) of A. bisporus tissue in a
      bioassay. These isolates were also identified as unique using repetitive
      extragenic palindromic PCR and biochemical analysis. Relationships between these
      33 blotch-causing organisms (BCO) and a further 22 selected pseudomonad species
      were inferred by phylogenetic analyses of near-full-length 16S rRNA gene
      nucleotide sequences. The 33 BCO isolates were observed to be distributed
      throughout the Pseudomonas fluorescens intrageneric cluster. These results show
      that in addition to known BCO (P. tolaasii, P. gingeri, and Pseudomonas
      reactans), a number of diverse pseudomonad species also have the ability to cause
      blotch diseases with various discolorations. Furthermore, observation of ginger
      blotch discoloration of A. bisporus being independently caused by many different
      pseudomonad species impacts on the homogeneity and classification of the
      previously described P. gingeri.

PMID- 11526039
TI  - Mapping microbial biodiversity.
AB  - We report the development of a prototype database that "maps" microbial diversity
      in the context of the geochemical and geological environment and geographic
      location. When it is fully implemented, scientists will be able to conduct
      database searches, construct maps containing the information of interest,
      download files, and enter data over the Internet.

PMID- 11526040
TI  - New spatially explicit method for detecting extracellular protease activity in
      biofilms.
AB  - A novel method of detecting extracellular protease activity at biofilm-substratum
      interfaces was developed. This method utilizes fluorescent molecules bound to
      cellulose substrata with a lectin. Extracellular proteases degrade the lectin and
      release the fluorochrome into solution. This new technique and a standard
      dissolved-substrate assay detected similar responses of biofilm extracellular
      protease activity to experimental manipulation of N supply. Combination of this
      technique with confocal scanning laser microscopy allowed direct visualization of
      microspatial patterns of bacterial distribution and extracellular protease
      activity at the biofilm-substratum interface.

PMID- 11526041
TI  - Lytic and lysogenic infection of diverse Escherichia coli and Shigella strains
      with a verocytotoxigenic bacteriophage.
AB  - A verocytotoxigenic bacteriophage isolated from a strain of enterohemorrhagic
      Escherichia coli O157, into which a kanamycin resistance gene (aph3) had been
      inserted to inactivate the verocytotoxin gene (vt2), was used to infect
      Enterobacteriaceae strains. A number of Shigella and E. coli strains were
      susceptible to lysogenic infection, and a smooth E. coli isolate (O107) was also
      susceptible to lytic infection. The lysogenized strains included different smooth
      E. coli serotypes of both human and animal origin, indicating that this
      bacteriophage has a substantial capacity to disseminate verocytotoxin genes. A
      novel indirect plaque assay utilizing an E. coli recA441 mutant in which phage
      infected cells can enter only the lytic cycle, enabling detection of all
      infective phage, was developed.

PMID- 11526042
TI  - Physiological characterization of Pseudomonas putida DOT-T1E tolerance to p
      hydroxybenzoate.
AB  - Pseudomonas putida DOT-T1E was isolated as a toluene-tolerant strain. We show
      that it is also able to grow on high concentrations (up to 17 g/liter [123 mM])
      of p-hydroxybenzoate (4HBA). Tolerance to this aromatic carboxylic acid (up to 30
      g/liter [217 mM]) is improved by preexposing the cells to low 4HBA
      concentrations; the adaptation process is caused by the substrate itself rather
      than by products resulting from its metabolism. The mechanisms of 4HBA tolerance
      seem to involve increased rigidity of the cell membrane as a result of a decrease
      in the cis/trans ratio of unsaturated fatty acids. In addition, energy-dependent
      efflux systems seem to operate in the exclusion of 4HBA from the cell membranes.

PMID- 11526043
TI  - Degradation of 3-methylpyridine and 3-ethylpyridine by Gordonia nitida LE31.
AB  - Cells of Gordonia nitida LE31 grown on 3-methylpyridine degraded 3-ethylpyridine
      without a lag time and vice versa. Cyclic intermediates were not detected, but
      formic acid was identified as a metabolite. Degradation of levulinic acid was
      induced in cells grown on 3-methylpyridine and 3-ethylpyridine. Levulinic
      aldehyde dehydrogenase and formamidase activities were higher in cells grown on 3
      methylpyridine and 3-ethylpyridine than in cells grown on acetate. These data
      indicate that 3-methylpyridine and 3-ethylpyridine were degraded via a new
      pathway involving C-2-C-3 ring cleavage.

PMID- 11526044
TI  - Generation of a novel Saccharomyces cerevisiae strain that exhibits strong
      maltose utilization and hyperosmotic resistance using nonrecombinant techniques.
AB  - A yeast strain capable of leavening both unsugared and sweet bread dough
      efficiently would reduce the necessity of carrying out the expensive procedure of
      producing multiple baker's yeast strains. But issues involving the use of
      genetically modified foods have rendered the use of recombinant techniques for
      developing yeast strains controversial. Therefore, we used strong selection and
      screening systems in conjunction with traditional mass mating techniques to
      develop a strain of Saccharomyces cerevisiae that efficiently leavens both types
      of dough.

PMID- 11526045
TI  - Biosorption of copper by a bacterial biofilm on a flexible polyvinyl chloride
      conduit.
AB  - Inexpensive technologies with less-than-optimal efficiencies as a strategy for
      countering economic restraints to pollution control have been evaluated by using
      a laboratory-scale biotreatment process for copper-containing effluent.
      Economizing measures include the use of polyvinyl chloride (PVC) cylinders
      fashioned from commercially available flexible PVC conduit to support a biofilm
      that was cultured in an inexpensive medium prepared in wastewater. The biofilm
      was challenged by aqueous copper solution in a bioreactor and subsequently
      analyzed under a scanning electron microscope with energy-dispersive X-ray
      microanalysis.

PMID- 11526046
TI  - Anaerobic mineralization of stable-isotope-labeled 2-methylnaphthalene.
AB  - An active sulfate-reducing consortium that degrades 2-methylnaphthalene (2-MNAP)
      at rates of up to 25 microM x day(-1) was established. Degradation was inhibited
      in the presence of molybdate and ceased in the absence of sulfate. As much as 87%
      of 2-[14C]MNAP was mineralized to 14CO2. 2-Naphthoic acid (2-NA) was detected as
      a metabolite, and incubation with either deuterated 2-MNAP or [13C]bicarbonate
      indicates that 2-NA is the result of oxidation of the methyl group. Also detected
      were carboxylated 2-MNAPs, suggesting the presence of an alternative pathway for
      2-MNAP degradation.

PMID- 11526047
TI  - Biotransformation of malachite green by the fungus Cunninghamella elegans.
AB  - The filamentous fungus Cunninghamella elegans ATCC 36112 metabolized the
      triphenylmethane dye malachite green with a first-order rate constant of 0.029
      micromol x h(-1) (mg of cells)(-1). Malachite green was enzymatically reduced to
      leucomalachite green and also converted to N-demethylated and N-oxidized
      metabolites, including primary and secondary arylamines. Inhibition studies
      suggested that the cytochrome P450 system mediated both the reduction and the N
      demethylation reactions.

PMID- 11526048
TI  - Efficient system for directed integration into the Lactobacillus acidophilus and
      Lactobacillus gasseri chromosomes via homologous recombination.
AB  - An efficient method is described for the generation of site-specific chromosomal
      integrations in Lactobacillus acidophilus and Lactobacillus gasseri. The strategy
      is an adaptation of the lactococcal pORI system (K. Leenhouts, G. Venema, and J.
      Kok, Methods Cell Sci. 20:35-50, 1998) and relies on the simultaneous use of two
      plasmids. The functionality of the integration strategy was demonstated by the
      insertional inactivation of the Lactobacillus acidophilus NCFM lacL gene encoding
      beta-galactosidase and of the Lactobacillus gasseri ADH gusA gene encoding beta
      glucuronidase.

PMID- 11526049
TI  - Diversity and distribution in hypersaline microbial mats of bacteria related to
      Chloroflexus spp.
AB  - Filamentous bacteria containing bacteriochlorophylls c and a were enriched from
      hypersaline microbial mats. Based on phylogenetic analyses of 16S rRNA gene
      sequences, these organisms form a previously undescribed lineage distantly
      related to Chloroflexus spp. We developed and tested a set of PCR primers for the
      specific amplification of 16S rRNA genes from filamentous phototrophic bacteria
      within the kingdom of "green nonsulfur bacteria." PCR products recovered from
      microbial mats in a saltern in Guerrero Negro, Mexico, were subjected to cloning
      or denaturing gradient gel electrophoresis and then sequenced. We found evidence
      of a high diversity of bacteria related to Chloroflexus which exhibit different
      distributions along a gradient of salinity from 5.5 to 16%.

PMID- 11526051
TI  - Quantitative comparisons of 16S rRNA gene sequence libraries from environmental
      samples.
AB  - To determine the significance of differences between clonal libraries of
      environmental rRNA gene sequences, differences between homologous coverage
      curves, CX(D), and heterologous coverage curves, CXY(D), were calculated by a
      Cramer-von Mises-type statistic and compared by a Monte Carlo test procedure.
      This method successfully distinguished rRNA gene sequence libraries from soil and
      bioreactors and correctly failed to find differences between libraries of the
      same composition.

PMID- 11526050
TI  - Susceptibility of a field-derived, Bacillus thuringiensis-resistant strain of
      diamondback moth to in vitro-activated Cry1Ac toxin.
AB  - Resistant and susceptible populations of the diamondback moth (Plutella
      xylostella) were tested with crystalline, solubilized, and partially and fully
      activated forms of the Bacillus thuringiensis Cry1Ac delta-endotoxin. Fully
      activated toxin greatly reduced the resistance ratio (ratio of the 50% lethal
      concentration for the resistant population to that for the susceptible
      population) of the resistant population, suggesting that a defect in toxin
      activation is a major resistance mechanism.

PMID- 11526052
TI  - Dehalogenation of chlorinated hydroxybiphenyls by fungal laccase.
AB  - We have investigated the transformation of chlorinated hydroxybiphenyls by
      laccase produced by Pycnoporus cinnabarinus. The compounds used were transformed
      to sparingly water-soluble colored precipitates which were identified by gas
      chromatography-mass spectrometry as oligomerization products of the chlorinated
      hydroxybiphenyls. During oligomerization of 2-hydroxy-5-chlorobiphenyl and 3
      chloro-4-hydroxybiphenyl, dechlorinated C---C-linked dimers were formed,
      demonstrating the dehalogenation ability of laccase. In addition to these
      nonhalogenated dimers, both monohalogenated and dihalogenated dimers were
      identified.

PMID- 11526053
TI  - Rapid confirmation of Clostridium perfringens by using chromogenic and
      fluorogenic substrates.
AB  - The use of 4-methylumbelliferyl phosphate (MUP) and ortho-nitrophenyl-beta-D
      galactopyranoside (ONPG) for the identification of Clostridium perfringens was
      investigated. A liquid assay containing both MUP and ONPG was a highly specific
      alternative method for C. perfringens confirmation, reducing incubation time from
      48 to only 4 h. The assay solution is easy to prepare, does not require anaerobic
      conditions for use, and has an extended shelf life.

PMID- 11526054
TI  - Incidence of virulence factors and antibiotic resistance among Enterococci
      isolated from food.
AB  - The incidence of virulence factors among 48 Enterococcus faecium and 47
      Enterococcus faecalis strains from foods and their antibiotic susceptibility were
      investigated. No strain was resistant to all antibiotics, and for some strains,
      multiple resistances were observed. Of E. faecium strains, 10.4% were positive
      for one or more virulence determinants, compared to 78.7% of E. faecalis strains.
      Strains exhibiting virulence traits were not necessarily positive for all traits;
      thus, the incidence of virulence factors may be considered to be strain specific.

PMID- 11526055
TI  - In vivo 23Na nuclear magnetic resonance study of maintenance of a sodium gradient
      in the ruminal bacterium Fibrobacter succinogenes S85.
AB  - Sodium gradients (DeltapNa) were measured in resting cells of Fibrobacter
      succinogenes by in vivo 23Na nuclear magnetic resonance using Tm(DOTP)5-
      [thulium(III) 1,4,7,10-tetraazacyclododecane-N',N",N"'-tetramethylenephosphonate]
      as the shift reagent. This bacterium was able to maintain a DeltapNa of -55 to 
      40 mV for extracellular sodium concentrations ranging from 30 to 200 mM.
      Depletion of Na+ ions during the washing steps led to irreversible damage
      (modification of glucose metabolism and inability to maintain a sodium gradient).

PMID- 11526057
TI  - Metabolism of pelagic cephalopods as a function of habitat depth: a reanalysis
      using phylogenetically independent contrasts.

PMID- 11526056
TI  - Genetic diversity of Nostoc symbionts endophytically associated with two
      bryophyte species.
AB  - The diversity of the endophytic Nostoc symbionts of two thalloid bryophytes, the
      hornwort Anthoceros fusiformis and the liverwort Blasia pusilla, was examined
      using the tRNA(Leu) (UAA) intron sequence as a marker. The results confirmed that
      many different Nostoc strains are involved in both associations under natural
      conditions in the field. The level of Nostoc diversity within individual
      bryophyte thalli varied, but single DNA fragments were consistently amplified
      from individual symbiotic colonies. Some Nostoc strains were widespread and were
      detected from thalli collected from different field sites and different years.
      These findings indicate a moderate level of spatial and temporal continuity in
      bryophyte-Nostoc symbioses.

PMID- 11526058
TI  - Signaling via water currents in behavioral interactions of snapping shrimp
      (Alpheus heterochaelis).
AB  - The snappping shrimp Alpheus heterochaelis produces a variety of different water
      currents during intraspecific encounters and interspecific interactions with
      small sympatric crabs (Eurypanopeus depressus). We studied the mechanisms of
      current production in tethered shrimp and the use of the different currents in
      freely behaving animals. The beating of the pleopods results in strong
      posteriorly directed currents. Although they reach rather far, these currents
      show no distinctions when directed toward different opponents. Gill currents are
      produced by movements of the scaphognathites (the exopodites of the second
      maxillae) and can then be deflected laterally by movements of the exopodites of
      the first and second maxillipeds. These frequent but slow lateral gill currents
      are most probably used to enhance chemical odor perception. The fast and focused,
      anteriorly directed gill currents, however, represent a powerful tool in
      intraspecific signaling, because they reach the chemo- and mechanosensory
      antennules of the opponent more often than any other currents and also because
      they are produced soon after previous contacts between the animals. They may
      carry chemical information about the social status of their producers since
      dominant shrimp release more anterior gill currents and more water jets than
      subordinate animals in intrasexual interactions.

PMID- 11526059
TI  - Methionine-enkephalin induces hyperglycemia through eyestalk hormones in the
      estuarine crab Scylla serrata.
AB  - The hypothesis is tested that methionine-enkephalin, a hormone produced in and
      released from eyestalk of crustaceans, produces hyperglycemia indirectly by
      stimulating the release of hyperglycemic hormone from the eyestalks. Injection of
      methionine-enkephalin leads to hyperglycemia and hyperglucosemia in the estuarine
      crab Scylla serrata in a dose-dependent manner. Decreases in total carbohydrate
      (TCHO) and glycogen levels of hepatopancreas and muscle with an increase in
      phosphorylase activity were also observed in intact crabs after methionine
      enkephalin injection. Eyestalk ablation depressed hemolymph glucose (19%) and
      TCHO levels (22%), with an elevation of levels of TCHO and glycogen of
      hepatopancreas and muscle. Tissue phosphorylase activity decreased significantly
      during bilateral eyestalk ablation. Administration of methionine-enkephalin into
      eyestalkless crabs caused no significant alterations in these parameters when
      compared to eyestalk ablated crabs. These results support the hypothesis that
      methionine-enkephalin produces hyperglycemia in crustaceans by triggering release
      of hyperglycemic hormone from the eyestalks.

PMID- 11526060
TI  - Theoretical and experimental dissection of gravity-dependent mechanical
      orientation in gravitactic microorganisms.
AB  - Mechanisms of gravitactic behaviors of aquatic microorganisms were investigated
      in terms of their mechanical basis of gravity-dependent orientation. Two
      mechanical mechanisms have been considered as possible sources of the orientation
      torque generated on the inert body. One results from the differential density
      within an organism (the gravity-buoyancy model) and the other from the
      geometrical asymmetry of an organism (the drag-gravity model). We first
      introduced a simple theory that distinguishes between these models by measuring
      sedimentation of immobilized organisms in a medium of higher density than that of
      the organisms. Ni2+-immobilized cells of Paramecium caudatum oriented downwards
      while floating upwards in the Percoll-containing hyper-density medium but
      oriented upwards while sinking in the hypo-density control medium. This means
      that the orientation of Paramecium is mechanically biased by the torque generated
      mainly due to the anterior location of the reaction center of hydrodynamic stress
      relative to those of buoyancy and gravity; thus the torque results from the
      geometrical fore-aft asymmetry and is described by the drag-gravity model. The
      same mechanical property was demonstrated in gastrula larvae of the sea urchin by
      observing the orientation during sedimentation of the KCN-immobilized larvae in
      media of different density: like the paramecia, the gastrulae oriented upwards in
      hypo-density medium and downwards in hyper-density medium. Immobilized pluteus
      larvae, however, oriented upwards regardless of the density of the medium. This
      indicates that the orientation of the pluteus is biased by the torque generated
      mainly due to the posterior location of the reaction center of gravity relative
      to those of buoyancy and hydrodynamic stress; thus the torque results from the
      fore-aft asymmetry of the density distribution and is described by the gravity
      buoyancy model. These observations indicate that, during development, sea urchin
      larvae change the mechanical mechanism for the gravitactic orientation. Evidence
      presented in the present paper demonstrates a definite relationship between the
      morphology and the gravitactic behavior of microorganisms.

PMID- 11526061
TI  - Synthesis of several light-harvesting complex I polypeptides is blocked by
      cycloheximide in symbiotic chloroplasts in the sea slug, Elysia chlorotica
      (Gould): a case for horizontal gene transfer between alga and animal?
AB  - The chloroplast symbiosis between the ascoglossan (=Sacoglossa) sea slug Elysia
      chlorotica and plastids from the chromophytic alga Vaucheria litorea is the
      longest-lived relationship of its kind known, lasting up to 9 months. During this
      time, the plastids continue to photosynthesize in the absence of the algal
      nucleus at rates sufficient to meet the nutritional needs of the slugs. We have
      previously demonstrated that the synthesis of photosynthetic proteins occurs
      while the plastids reside within the diverticular cells of the slug. Here, we
      have identified several of these synthesized proteins as belonging to the nuclear
      encoded family of polypeptides known as light-harvesting complex I (LHCI). The
      synthesis of LHCI is blocked by the cytosolic ribosomal inhibitor cycloheximide
      and proceeds in the presence of chloramphenicol, a plastid ribosome inhibitor,
      indicating that the gene encoding LHCI resides in the nuclear DNA of the slug.
      These results suggest that a horizontal transfer of the LHCI gene from the alga
      to the slug has taken place.

PMID- 11526062
TI  - Asexual reproduction in Pygospio elegans claparede (Annelida, Polychaeta) in
      relation to parasitism by Lepocreadium setiferoides (Miller and Northup)
      (Platyhelminthes, Trematoda).
AB  - Life-history theory predicts that parasitized hosts should alter their investment
      in reproduction in ways that maximize host reproductive success. I examined the
      timing of asexual reproduction (fragmentation and regeneration) in the polychaete
      annelid Pygospio elegans experimentally exposed to cercariae of the trematode
      Lepocreadium setiferoides. Consistent with adaptive host response, polychaetes
      that became infected by metacercariae of trematodes fragmented sooner than
      unexposed controls. Parasites were not directly associated with fission in that
      exposed polychaetes that did not become infected also fragmented earlier than
      controls. For specimens of P. elegans that were not exposed to trematodes, new
      fragments that contained original heads were larger than those that contained
      original tails, whereas original head and tail fragments did not differ in size
      for infected polychaetes. In infected specimens, metacercariae were equally
      represented in original head and tail fragments and were more likely to be found
      in whichever fragment was larger. Despite early reproduction, parasitism was
      still costly because populations of P. elegans exposed to parasites were smaller
      than controls when measured 8 weeks later and because exposure to cercariae
      reduced survivorship of newly divided polychaetes. Taken together, my results
      suggest that early fragmentation is a host response to minimize costs associated
      with parasitism.

PMID- 11526063
TI  - Delayed insemination results in embryo mortality in a brooding ascidian.
AB  - We explored the effects of temporal variation in sperm availability on
      fertilization and subsequent larval development in the colonial ascidian
      Botryllus schlosseri, a brooding hermaphrodite that has a sexual cycle linked to
      an asexual zooid replacement cycle. We developed a method to quantify the timing
      of events early in this cycle, and then isolated colonies before the start of the
      cycle and inseminated them at various times. Colony-wide fertilization levels
      (assayed by early cleavage) increased from zero to 100% during the period when
      the siphons of a new generation of zooids were first opening, and remained high
      for 24 h before slowly declining over the next 48 h. Because embryos are brooded
      until just before the zooids degenerate at the end of a cycle, delayed
      fertilization might also affect whether embryos can complete development within
      the cycle. Consequently, we also determined the effect of delayed insemination on
      successful embryo development through larval release and metamorphosis. When
      fertilization was delayed beyond the completion of siphon opening, there was an
      exponential decline in the percentage of eggs that ultimately produced a
      metamorphosed larva at the end of the cycle. Thus, even though the majority of
      oocytes can be fertilized when insemination is delayed for up to 48 h, the
      resulting embryos cannot complete development before the brooding zooids
      degenerate.

PMID- 11526064
TI  - Morula cells as the major immunomodulatory hemocytes in ascidians: evidences from
      the colonial species Botryllus schlosseri.
AB  - Immunocytochemical methods were used to study the presence and distribution of IL
      1-alpha- and TNF-alpha-like molecules in the hemocytes of the colonial ascidian
      Botryllus schlosseri. Only a few unstimulated hemocytes were positive to both the
      antibodies used. When the hemocytes were stimulated with either mannan or phorbol
      12-mono-myristate, the phagocytes were not significantly changed in their number,
      staining intensity, or cell morphology. In contrast, stimulated morula cells were
      intensely labeled, indicating that these cells play an important immunomodulatory
      role.

PMID- 11526065
TI  - Molecular evidence that Sclerolinum brattstromi is closely related to
      vestimentiferans, not to frenulate pogonophorans (Siboglinidae, Annelida).
AB  - Siboglinids, previously referred to as pogonophorans, have typically been divided
      into two groups, frenulates and vestimentiferans. Adults of these marine
      protostome worms lack a functional gut and harbor endosymbiotic bacteria.
      Frenulates usually live in deep, sedimented reducing environments, and
      vestimentiferans inhabit hydrothermal vents and sulfide-rich hydrocarbon seeps.
      Taxonomic literature has often treated frenulates and vestimentiferans as sister
      taxa. Sclerolinum has traditionally been thought to be a basal siboglinid that
      was originally regarded as a frenulate and later as a third lineage of
      siboglinids, Monilifera. Evidence from the 18S nuclear rDNA gene and the 16S
      mitochondrial rDNA gene presented here shows that Sclerolinum is the sister clade
      to vestimentiferans although it lacks the characteristic morphology (i.e., a
      vestimentum). The rDNA data confirm the contention that Sclerolinum is different
      from frenulates, and further supports the idea that siboglinid evolution has been
      driven by a trend toward increased habitat specialization. The evidence now
      available indicates that vestimentiferans lack the molecular diversity expected
      of a group that has been argued to have Silurian or possibly Cambrian origins.

PMID- 11526066
TI  - Effect of cloning rate on fitness-related traits in two marine hydroids.
AB  - Hydractinia symbiolongicarpus and Podocoryna carnea are colonial marine hydroids
      capable of reproducing both sexually and asexually. Asexual reproduction, by
      colony fragmentation, produces a genetic clone of the parent colony. This study
      examines the effect of very different cloning rates on colony growth rate, oxygen
      uptake rate, and colony morphology. Colonies of one clone of each species were
      maintained for an extended time in two treatments: in a state of constant
      vegetative growth by repeated cloning, and in a state restricted from vegetative
      growth (no cloning). For both species, tissue explants taken from the growing
      colonies grew more slowly than similar explants taken from the restricted
      colonies. For one species, tissue explants from the growing colonies used oxygen
      at a higher rate than similar explants from restricted colonies; for the other
      species, no difference was detected, although the sample size was small. For both
      species, tissue explants from restricted colonies formed more circular, "sheet
      like" shapes, whereas those from their growing counterparts formed more
      irregular, "runner-like" shapes. After these experiments, in the third winter of
      treatment, all colonies experienced a severe tissue regression. Within 6 months
      after this event, the colonies had regrown to their former sizes. A growth assay
      at this point revealed no difference in growth rate, possibly suggesting an
      epigenetic basis for these results. Changes in clonal growth rates and morphology
      correlated with variation in fragmentation rate might affect the ecology of these
      and other clonal organisms.

PMID- 11526068
TI  - Biogeography of Asterias: North Atlantic climate change and speciation.
AB  - Fossil evidence suggests that the seastar genus Asterias arrived in the North
      Atlantic during the trans-Arctic interchange around 3.5 Ma. Previous genetic and
      morphological studies of the two species found in the Atlantic today suggested
      two possible scenarios for the speciation of A. rubens and A. forbesi. Through
      phylogenetic and population genetic analysis of data from a portion of the
      cytochrome oxidase I mitochondrial gene and a fragment of the ribosomal internal
      transcribed spacer region, I show that the formation of the Labrador Current 3.0
      Ma was probably responsible for the initial vicariance of North Atlantic Asterias
      populations. Subsequent adaptive evolution in A. forbesi was then possible in
      isolation from the European species A. rubens. The contact zone between these two
      species formed recently, possibly due to a Holocene founding event of A. rubens
      in New England and the Canadian Maritimes.

PMID- 11526067
TI  - Egg longevity and time-integrated fertilization in a temperate sea urchin
      (Strongylocentrotus droebachiensis).
AB  - Recent field experiments have suggested that fertilization levels in sea urchins
      (and other broadcast spawners that release their gametes into the water column)
      may often be far below 100%. However, past experiments have not considered the
      potentially positive combined effects of an extended period of egg longevity and
      the release of gametes in viscous fluids (which reduces dilution rates). In a
      laboratory experiment, we found that eggs of the sea urchin Strongylocentrotus
      droebachiensis had high viability for 2 to 3 d. Fertilization levels of eggs held
      in sperm-permeable egg baskets in the field and exposed to sperm slowly diffusing
      off a spawning male increased significantly with exposure from 15 min to 3 h. In
      a field survey of time-integrated fertilizations (over 24, 48, and 72 h) during
      natural sperm release events, eggs held in baskets accrued fertilizations over as
      much as 48 h and attained fairly high fertilization levels. Our results suggest
      that an extended period of egg longevity and the release of gametes in viscous
      fluids may result in higher natural fertilization levels than currently expected
      from short-term field experiments.

PMID- 11526069
TI  - Systematics and biogeography of the jellyfish Aurelia labiata (Cnidaria:
      Scyphozoa).
AB  - The hypothesis that the common eastern North Pacific Aurelia is A. aurita is
      falsified with morphological analysis. The name Aurelia labiata is resurrected,
      and the species is redescribed, to refer to medusae differing from A. aurita by a
      suite of characters related to a broad and elongated manubrium. Specifically, the
      oral arms are short, separated by and arising from the base of the fleshy
      manubrium, and the planulae are brooded upon the manubrium itself, rather than on
      the oral arms. Aurelia aurita possesses no corresponding enlarged structure.
      Furthermore, the number of radial canals is typically much greater in A. labiata,
      and thus the canals often appear more anastomosed than in A. aurita. Finally,
      most A. labiata medusae possess a 16-scalloped bell margin, whereas the margin is
      8-scalloped in most A. aurita. Separation of the two forms has previously been
      noted on the basis of allozyme and isozyme analyses and on the histology of the
      neuromuscular system. Partial 18S rDNA sequencing corroborates these findings.
      Three distinct morphotypes of A. labiata, corresponding to separate marine
      bioprovinces, have been identified among 17 populations from San Diego,
      California, to Prince William Sound, Alaska. The long-undisputed species A.
      limbata may be simply a color morph of A. labiata, or a species within a yet
      unelaborated A. labiata species complex. The first known introduction of Aurelia
      cf. aurita into southern California waters is documented. Although traditional
      jellyfish taxonomy tends to recognize many species as cosmopolitan or nearly so,
      these results indicate that coastal species, such as A. labiata, may experience
      rapid divergence among isolated populations, and that the taxonomy of such
      species should therefore be scrutinized with special care.

PMID- 11526070
TI  - The BMP signaling pathway is required together with the FGF pathway for notochord
      induction in the ascidian embryo.
AB  - The 40 notochord cells of the ascidian tadpole invariably arise from two
      different lineages: the primary (A-line) and the secondary (B-line) lineages. It
      has been shown that the primary notochord cells are induced by presumptive
      endoderm blastomeres between the 24-cell and the 64-cell stage. Signaling through
      the fibroblast growth factor (FGF) pathway is required for this induction. We
      have investigated the role of the bone morphogenetic protein (BMP) pathway in
      ascidian notochord formation. HrBMPb (the ascidian BMP2/4 homologue) is expressed
      in the anterior endoderm at the 44-cell stage before the completion of notochord
      induction. The BMP antagonist Hrchordin is expressed in a complementary manner in
      all surrounding blastomeres and appears to be a positive target of the BMP
      pathway. Unexpectedly, chordin overexpression reduced formation of both primary
      and secondary notochord. Conversely, primary notochord precursors isolated prior
      to induction formed notochord in presence of BMP-4 protein. While bFGF protein
      had a similar activity, notochord precursors showed a different time window of
      competence to respond to BMP-4 and bFGF. Our data are consistent with bFGF acting
      from the 24-cell stage, while BMP-4 acts during the 44-cell stage. However,
      active FGF signaling was also required for induction by BMP-4. In the secondary
      lineage, notochord specification also required two inducing signals: an FGF
      signal from anterior and posterior endoderm from the 24-cell stage and a BMP
      signal from anterior endoderm during the 44-cell stage.

PMID- 11526071
TI  - Redundant function of Runt Domain binding partners, Big brother and Brother,
      during Drosophila development.
AB  - The Core Binding Factor is a heterodimeric transcription factor complex in
      vertebrates that is composed of a DNA binding alpha-subunit and a non-DNA binding
      beta-subunit. The alpha-subunit is encoded by members of the Runt Domain family
      of proteins and the beta-subunit is encoded by the CBF beta gene. In Drosophila,
      two genes encoding alpha-subunits, runt and lozenge, and two genes encoding beta
      subunits, Big brother and Brother, have been previously identified. Here, a
      sensitized genetic screen was used to isolate mutant alleles of the Big brother
      gene. Expression studies show that Big brother is a nuclear protein that co
      localizes with both Lozenge and Runt in the eye imaginal disc. The nuclear
      localization and stability of Big brother protein is mediated through the
      formation of heterodimeric complexes between Big brother and either Lozenge or
      Runt. Big brother functions with Lozenge during cell fate specification in the
      eye, and is also required for the development of the embryonic PNS. ds-RNA
      mediated genetic interference experiments show that Brother and Big brother are
      redundant and function together with Runt during segmentation of the embryo.
      These studies highlight a mechanism for transcriptional control by a Runt Domain
      protein and a redundant pair of partners in the specification of cell fate during
      development.

PMID- 11526072
TI  - The sex determination master switch, Sex-lethal, responds to Hedgehog signaling
      in the Drosophila germline.
AB  - Sex-lethal is the Drosophila melanogaster sex determination master switch. It is
      also required in female germ cells to control mitosis and meiotic recombination.
      As early germ cells mature, distinct changes in both Sex-lethal protein levels
      and localization occur. By manipulating the levels of Hedgehog and making
      germline clones of components in the hedgehog signaling pathway, we demonstrate
      that Hedgehog affects the nuclear translocation of Sex-lethal and the levels of
      the protein in early germ cells. This effect is mediated primarily through
      degradation. Consistent with the Hedgehog pathway regulating Sex-lethal, we find
      Sex-lethal in a complex with Fused and Costal-2, both downstream components of
      the pathway. This is the first demonstration that downstream components of the
      Hedgehog signaling pathway regulate a target other than Cubitus interruptus.

PMID- 11526073
TI  - Epidermal control of floral organ identity by class B homeotic genes in
      Antirrhinum and Arabidopsis.
AB  - To assess the contribution of the epidermis to the control of petal and stamen
      organ identity, we have used transgenic Antirrhinum and Arabidopsis plants that
      expressed the Antirrhinum class B homeotic transcription factors DEFICIENS (DEF)
      and GLOBOSA (GLO) in the epidermis. Transgene expression was controlled by the
      ANTIRRHINUM FIDDLEHEAD (AFI) promoter, which directs gene expression to the L1
      meristematic layer and, later, to the epidermis of differentiating organs.
      Transgenic epidermal DEF and GLO chimeras display similar phenotypes, suggesting
      similar epidermal contributions by the two class B genes in ANTIRRHINUM:
      Epidermal B function autonomously controls the differentiation of Antirrhinum
      petal epidermal cell types, but cannot fully control the pattern of cell
      divisions and the specification of sub-epidermal petal cell-identity by epidermal
      signalling. This non-autonomous control is enhanced if the endogenous class B
      genes can be activated from the epidermis. The developmental influence of
      epidermal B function in Antirrhinum stamen development is very limited. In
      contrast, epidermal B function in Arabidopsis can control most if not all
      epidermal and sub-epidermal differentiation events in petals and stamens, without
      any contribution from the endogenous class B genes. Possible reasons for
      differences in the efficacy of B-function-mediated cell communication between the
      two species are discussed. Interestingly, our experiments uncovered partial
      incompatibility between class B functional homologues. Although the
      DEFICIENS/PISTILLATA heterodimer is functional in transgenic Arabidopsis plants,
      the APETALA3/GLOBOSA heterodimer is not.

PMID- 11526074
TI  - Neurogenesis in the spider Cupiennius salei.
AB  - To uncover similarities and differences in neurogenesis in arthropod groups, we
      have studied the ventral neuroectoderm of the spider Cupiennius salei
      (Chelicerata, Aranea, Ctenidae). We found that invaginating cell groups arose
      sequentially, at stereotyped positions in each hemisegment and in separate waves,
      comparable with the generation of neuroblasts in Drosophila. However, we found no
      evidence for proliferating stem cells that would be comparable with the
      neuroblasts. Instead, the whole group of invaginating cells was directly
      recruited to the nervous system. The invagination process is comparable with
      Drosophila, with the cells attaining a bottle-shaped form with the nuclei moving
      inwards, while actin-rich cell processes remain initially connected to the
      surface of the epithelium. This general pattern is also found in another spider,
      Pholcus phalangioides, and appears thus to be conserved at least among the
      Araneae. We have identified two basic helix-loop-helix encoding genes -- CsASH1
      and CsASH2 -- that share sequence similarities with proneural genes from other
      species. Functional analysis of the genes by double-stranded RNA interference
      revealed that CsASH1 was required for the formation of the invagination sites and
      the process of invagination itself, whereas CsASH2 seemed to be required for the
      differentiation of the cells into neurones. Our results suggest that the basic
      processes of neurogenesis, as well as proneural gene function is conserved among
      arthropods, apart of the lack of neuroblast-like stem cells in spiders.

PMID- 11526075
TI  - The EGF receptor and notch signaling pathways control the initiation of the
      morphogenetic furrow during Drosophila eye development.
AB  - The onset of pattern formation in the developing Drosophila retina begins with
      the initiation of the morphogenetic furrow, the leading edge of a wave of retinal
      development that transforms a uniform epithelium, the eye imaginal disc into a
      near crystalline array of ommatidial elements. The initiation of this wave of
      morphogenesis is under the control of the secreted morphogens Hedgehog (Hh),
      Decapentaplegic (Dpp) and Wingless (Wg). We show that the Epidermal Growth Factor
      Receptor and Notch signaling cascades are crucial components that are also
      required to initiate retinal development. We also show that the initiation of the
      morphogenetic furrow is the sum of two genetically separable processes: (1) the
      'birth' of pattern formation at the posterior margin of the eye imaginal disc;
      and (2) the subsequent 'reincarnation' of retinal development across the
      epithelium.

PMID- 11526076
TI  - A dual function of phyllopod in Drosophila external sensory organ development:
      cell fate specification of sensory organ precursor and its progeny.
AB  - During Drosophila external sensory organ development, one sensory organ precursor
      (SOP) arises from a proneural cluster, and undergoes asymmetrical cell divisions
      to produce an external sensory (es) organ made up of different types of daughter
      cells. We show that phyllopod (phyl), previously identified to be essential for
      R7 photoreceptor differentiation, is required in two stages of es organ
      development: the formation of SOP cells and cell fate specification of SOP
      progeny. Loss-of-function mutations in phyl result in failure of SOP formation,
      which leads to missing bristles in adult flies. At a later stage of es organ
      development, phyl mutations cause the first cell division of the SOP lineage to
      generate two identical daughters, leading to the fate transformation of neurons
      and sheath cells to hair cells and socket cells. Conversely, misexpression of
      phyl promotes ectopic SOP formation, and causes opposite fate transformation in
      SOP daughter cells. Thus, phyl functions as a genetic switch in specifying the
      fate of the SOP cells and their progeny. We further show that seven in absentia
      (sina), another gene required for R7 cell fate differentiation, is also involved
      in es organ development. Genetic interactions among phyl, sina and tramtrack
      (ttk) suggest that phyl and sina function in bristle development by antagonizing
      ttk activity, and ttk acts downstream of phyl. It has been shown previously that
      Notch (N) mutations induce formation of supernumerary SOP cells, and
      transformation from hair and socket cells to neurons. We further demonstrate that
      phyl acts epistatically to N. phyl is expressed specifically in SOP cells and
      other neural precursors, and its mRNA level is negatively regulated by N
      signaling. Thus, these analyses demonstrate that phyl acts downstream of N
      signaling in controlling cell fates in es organ development.

PMID- 11526077
TI  - FGF signals are involved in the differentiation of notochord cells and mesenchyme
      cells of the ascidian Halocynthia roretzi.
AB  - Differentiation of notochord cells and mesenchyme cells of the ascidian
      Halocynthia roretzi requires interactions with neighboring endodermal cells and
      previous experiments suggest that these interactions require fibroblast growth
      factor (FGF). In the present study, we examined the role of FGF in these
      interactions by disrupting signaling using the dominant negative form of the FGF
      receptor. An FGF receptor gene of H. roretzi (HrFGFR) is expressed both
      maternally and zygotically. The maternally expressed transcript was ubiquitously
      distributed in fertilized eggs and in early embryos. Zygotic expression became
      evident by the neurula stage and transcripts were detected in epidermal cells of
      the posterior half of embryos. Synthetic mRNA for the dominant negative form of
      FGFR, in which the intracellular tyrosine kinase domain was deleted, was injected
      into fertilized eggs to interfere with the possible function of HRFGFR: Injected
      eggs cleaved and gastrulated the same as the control embryos. Analyses of the
      expression of differentiation markers in the experimental embryos indicated that
      the differentiation of epidermal cells, muscle cells and endodermal cells was not
      affected significantly. However, manipulated embryos showed downregulation of
      notochord-specific Brachyury expression and failure of notochord cell
      differentiation, resulting in the development of tailbud embryos with shorted
      tails. The expression of an actin gene that is normally expressed in mesenchyme
      cells was also suppressed. These results suggest that FGF signals are involved in
      differentiation of notochord cells and mesenchyme cells in Halocynthia embryos.
      Furthermore, the patterning of a neuron-specific tubulin gene expression was
      disturbed, suggesting that the formation of the nervous system was directly
      affected by disrupting FGF signals or indirectly affected due to the disruption
      of normal notochord formation.

PMID- 11526078
TI  - Control of oligodendrocyte differentiation by the Nkx2.2 homeodomain
      transcription factor.
AB  - Oligodendrocytes are derived from glial precursors that arise from the ventral
      neural tube early in development. In the developing chicken CNS, oligodendrocyte
      progenitors selectively express Nkx2.2 homeodomain transcription factor, raising
      the possibility that Nkx2.2 may directly regulate oligogliogenesis. In this
      study, we have examined Nkx2.2 expression in rodent glial precursors and studied
      the effect of a loss of Nkx2.2 on oligodendrocyte and astrocyte differentiation.
      We show that Nkx2.2 is also expressed in mammalian oligodendrocyte progenitors
      and that the differentiation of MBP-positive and PLP-DM20-positive
      oligodendrocytes is dramatically retarded in Nkx2.2-null mutants along the entire
      rostrocaudal axis. In contrast, no effect is seen on astrocytic differentiation.
      Interestingly, absence of Nkx2.2 expression leads to a ventral expansion of the
      Olig1/Olig2 expression in neuroepithelial cells into the Nkx2.2 domain and a
      consequent increase in the production of Olig1/Olig2-positive and platelet
      derived growth factor receptor alpha-positive oligodendrocyte progenitors. These
      results strongly suggest that Nkx2.2 regulates the differentiation and/or
      maturation, but not the initial specification, of oligodendrocyte progenitors.
      Consistent with this suggestion, overproduction of Nkx2.2 protein in fibroblast
      cells can induce gene expression from the proteolipid protein promoter.

PMID- 11526080
TI  - Specification of bundle sheath cell fates during maize leaf development: roles of
      lineage and positional information evaluated through analysis of the tangled1
      mutant.
AB  - In leaves of the maize tangled1 (tan1) mutant, clusters of bundle sheath (BS)
      like cells extend several cells distant from the veins, in association with the
      single layer of BS cells around the vein. We show that the BS-like cell clusters
      in tan1 leaves result from the continued division of cells in the procambial/BS
      cell lineage that do not divide further in wild-type leaves. The ectopic BS-like
      cells accumulate the BS marker NADP-dependent malic enzyme but not the mesophyll
      cell marker phosphoenolpyruvate carboxylase, and exhibit thickened walls,
      suggesting that they differentiate as C4-type BS cells. We propose that bundle
      sheath cell fate can be conferred on some derivatives of procambial cell
      divisions in a manner that is heritable through multiple cell divisions and is
      position-independent.

PMID- 11526079
TI  - The ASK1 gene regulates B function gene expression in cooperation with UFO and
      LEAFY in Arabidopsis.
AB  - The Arabidopsis floral regulatory genes APETALA3 (AP3) and PISTILLATA (PI) are
      required for the B function according to the ABC model for floral organ identity.
      AP3 and PI expression are positively regulated by the LEAFY (LFY) and UNUSUAL
      FLORAL ORGANS (UFO) genes. UFO encodes an F-box protein, and we have shown
      previously that UFO genetically interacts with the ASK1 gene encoding a SKP1
      homologue; both the F-box containing protein and SKP1 are subunits of ubiquitin
      ligases. We show here that the ask1-1 mutation can enhance the floral phenotypes
      of weak lfy and ap3 mutants; therefore, like UFO, ASK1 also interacts with LFY
      and AP3 genetically. Furthermore, our results from RNA in situ hybridizations
      indicate that ASK1 regulates early AP3 and PI expression. These results support
      the idea that UFO and ASK1 together positively regulate AP3 and PI expression. We
      propose that the UFO and ASK1 proteins are components of a ubiquitin ligase that
      mediates the proteolysis of a repressor of AP3 and PI expression. Our genetic
      studies also indicate that ASK1 and UFO play a role in regulating the number of
      floral organ primordia, and we discuss possible mechanisms for such a regulation.

PMID- 11526081
TI  - Local retinoid signaling coordinates forebrain and facial morphogenesis by
      maintaining FGF8 and SHH.
AB  - Correlations between facial anomalies and brain defects are well characterized
      throughout the clinical literature, yet a developmental basis for this
      association has not been identified. We demonstrate that the frontonasal process,
      which gives rise to the mid- and upper face, and the forebrain are linked early
      in their morphogenesis by a local retinoid signaling event that maintains the
      expression of key regulatory molecules. First, we show that aldehyde
      dehydrogenase 6, which synthesizes the ligand, retinoic acid, is localized to the
      ventral epithelium of the presumptive frontonasal process of chick embryos. At
      least two retinoid receptors are expressed in adjacent populations of mesenchyme.
      Second, using synthetic pan-specific retinoid antagonists, we transiently inhibit
      the ability of retinoid receptors to bind retinoic acid in the rostral head and
      we generate embryos with a hypoplastic forebrain, fused eyes, and no frontonasal
      process-derived structures such as the upper beak. These defects are not due to
      eliminating mesenchymal progenitors, as neural crest cells still migrate into the
      frontonasal process, despite disruptions to retinoid signaling. Rather, these
      malformations result from loss of fibroblast growth factor 8 and sonic hedgehog
      expression, which leads to increased programmed cell death and decreased
      proliferation in the forebrain and frontonasal process. Most significantly, we
      can rescue the morphological defects by re-introducing retinoic acid, or
      fibroblast growth factor and sonic hedgehog proteins into antagonist-treated
      embryos. We propose that the local source of retinoic acid in the rostral head
      initiates a regulatory cascade that coordinates forebrain and frontonasal process
      morphogenesis.

PMID- 11526082
TI  - Suppression of head formation by Xmsx-1 through the inhibition of intracellular
      nodal signaling.
AB  - It is well established that in Xenopus, bone morphogenetic protein (BMP)
      ventralizes the early embryo through the activation of several target genes
      encoding homeobox proteins, some of which are known to be necessary and
      sufficient for ventralization. Here, we used an inhibitory form of Xmsx-1, one of
      BMP's targets, to examine its role in head formation. Interestingly, ventral
      overexpression of a dominant Xmsx-1 inhibitor induced an ectopic head with eyes
      and a cement gland in the ventral side of the embryo, suggesting that Xmsx-1 is
      normally required to suppress head formation in the ventral side. Supporting this
      observation, we also found that wild-type Xmsx-1 suppresses head formation
      through the inhibition of nodal signaling, which is known to induce head
      organizer genes such as cerberus, Xhex and Xdkk-1. We propose that negative
      regulation of the BMP/Xmsx-1 signal is involved not only in neural induction but
      also in head induction and formation. We further suggest that the inhibition of
      nodal signaling by Xmsx-1 may occur intracellularly, through interaction with
      Smads, at the level of the transcriptional complex, which activates the activin
      responsive element.

PMID- 11526083
TI  - Evolution of regeneration and fission in annelids: insights from engrailed- and
      orthodenticle-class gene expression.
AB  - The recent explosion of information on the role of regulatory genes in
      embryogenesis provides an excellent opportunity to study how these genes
      participate in post-embryonic developmental processes. We present a detailed
      comparison of regulatory gene expression during regeneration and asexual
      reproduction (by fission) in the segmented worm Pristina leidyi (Annelida:
      Oligochaeta). We isolated three genes from Pristina, one homolog of engrailed and
      two homologs of orthodenticle, and characterized their expression in different
      developmental contexts. In situ hybridization studies on worms undergoing normal
      growth, regeneration and fission demonstrate that in all three processes, Pl-en
      is expressed primarily in the developing nervous system, and Pl-Otx1 and Pl-Otx2
      are expressed primarily in the anterior body wall, foregut and developing nervous
      system. Our data reveal extensive similarities between expression during
      regeneration and fission, consistent with the idea that similar developmental
      processes underlie these two types of development. Thus, we argue that in these
      annelids fission may have evolved by recruitment of regenerative processes.
      Furthermore, by comparing our data to existing data from leech embryos, we find
      evidence that embryonic processes are re-deployed during regeneration and
      fission.

PMID- 11526084
TI  - The furry gene of Drosophila is important for maintaining the integrity of
      cellular extensions during morphogenesis.
AB  - The Drosophila imaginal cells that produce epidermal hairs, the shafts of sensory
      bristles and the lateral extensions of the arista are attractive model systems
      for studying the morphogenesis of polarized cell extensions. We now report the
      identification and characterization of furry, an essential Drosophila gene that
      is involved in maintaining the integrity of these cellular extensions during
      morphogenesis. Mutations in furry result in the formation of branched arista
      laterals, branched bristles and a strong multiple hair cell phenotype that
      consists of clusters of epidermal hairs and branched hairs. By following the
      morphogenesis of arista laterals in pupae, we have determined that the branched
      laterals are due to the splitting of individual laterals during elongation. In
      genetic mosaics furry was found to act cell autonomously in the wing. The
      phenotypes of double mutant cells argue that furry functions independently of the
      frizzled planar polarity pathway and that it probably functions in the same
      pathway as the tricornered gene. We used a P-element insertion allele as a tag to
      clone the furry gene and found it to be a large and complicated gene that encodes
      a pair of large conserved proteins of unknown biochemical function.

PMID- 11526085
TI  - The Drosophila proboscis is specified by two Hox genes, proboscipedia and Sex
      combs reduced, via repression of leg and antennal appendage genes.
AB  - The proboscis is one of the most highly modified appendages in Drosophila
      melanogaster. However, the phenotypes of proboscipedia (pb) mutants, which
      transform the proboscis into leg or antenna, indicate a basic homology among
      these limbs. Recent genetic studies have revealed a developmental system for
      patterning appendages and identified several genes required for limb development.
      Among these are: extradenticle (exd), homothorax (hth), dachshund (dac), Distal
      less (Dll) and spalt (sal). These limb genes have not been well studied in wild
      type mouthparts and their role if any in this appendage is not well understood.
      Here we demonstrate that the homeotic gene products Proboscipedia (Pb) and Sex
      combs reduced (Scr) regulate the limb genes in the labial disc to give rise to a
      unique type of appendage, the proboscis. Pb inhibits exd, dac and sal expression
      and downregulates DLL: This observation explains the ability of Pb to inhibit the
      effects of ectopically expressed trunk Hox genes in the proboscis, to suppress
      leg identity in the trunk and to transform antenna to maxillary palp. Scr
      suppresses sal expression and also downregulates Dll in the labial discs; discs
      mutant for both pb and Scr give rise to complete antennae, further demonstrating
      appendage homology. In the labial disc, Pb positively regulates transcription of
      Scr, whereas in the embryo, Scr positively regulates pb. Additionally, our
      results suggests a revised fate map of the labial disc. We conclude that the
      proboscis constitutes a genetically distinct type of appendage whose
      morphogenesis does not require several important components of leg and/or
      antennal patterning systems, but retains distal segmental homology with these
      appendages.

PMID- 11526086
TI  - CPEB phosphorylation and cytoplasmic polyadenylation are catalyzed by the kinase
      IAK1/Eg2 in maturing mouse oocytes.
AB  - In both vertebrates and invertebrates, the expression of several maternal mRNAs
      is regulated by cytoplasmic polyadenylation. In Xenopus oocytes, where most of
      the biochemical details of this process have been examined, polyadenylation is
      controlled by CPEB, a sequence-specific RNA binding protein. The activity of
      CPEB, which is to recruit cleavage and polyadenylation specificity factor (CPSF)
      and poly(A) polymerase (PAP) into an active cytoplasmic polyadenylation complex,
      is controlled by Eg2-catalyzed phosphorylation. Soon after CPEB phosphorylation
      and resulting polyadenylation take place, the interaction between maskin, a CPEB
      associated factor, and eIF4E, the cap-binding protein, is destroyed, which
      results in the recruitment of mRNA into polysomes. Polyadenylation also occurs in
      maturing mouse oocytes, although the biochemical events that govern the reaction
      in these cells are not known. In this study, we have examined the phosphorylation
      of CPEB and have assessed the necessity of this protein for polyadenylation in
      maturing mouse oocytes. Immunohistochemistry has revealed that all the factors
      that control polyadenylation and translation in Xenopus oocytes (CPEB, CPSF, PAP,
      maskin, and IAK1, the murine homologue of Eg2) are also present in the cytoplasm
      of mouse oocytes. After the induction of maturation, a kinase is activated that
      phosphorylates CPEB on a critical regulatory residue, an event that is essential
      for CPEB activity. A peptide that competitively inhibits the activity of IAK1/Eg2
      blocks the progression of meiosis in injected oocytes. Finally, a CPEB protein
      that acts as a dominant negative mutation because it cannot be phosphorylated by
      IAK1/Eg2, prevents cytoplasmic polyadenylation. These data indicate that
      cytoplasmic polyadenylation in mouse oocytes is mediated by IAK1/Eg2-catalyzed
      phosphorylation of CPEB.

PMID- 11526087
TI  - Aubergine encodes a Drosophila polar granule component required for pole cell
      formation and related to eIF2C.
AB  - In Drosophila oocytes, activation of Oskar translation from a transcript
      localized to the posterior pole is an essential step in the organization of the
      pole plasm, specialized cytoplasm that contains germline and abdominal body
      patterning determinants. Oskar is a component of polar granules, large particles
      associated with the pole plasm and the germline precursor pole cells of the
      embryo. aubergine mutants fail to translate oskar mRNA efficiently and are thus
      defective in posterior body patterning and pole cell formation. We have found
      that Aubergine protein is related to eukaryotic translation initiation factor 2C
      and suggest how it may activate translation. In addition, we found that Aubergine
      was recruited to the posterior pole in a vas-dependent manner and is itself a
      polar granule component. Consistent with its presence in these structures,
      Aubergine is required for pole cell formation independently of its initial role
      in oskar translation. Unlike two other known polar granule components, Vasa and
      Oskar, Aubergine remains cytoplasmic after pole cell formation, suggesting that
      the roles of these proteins diverge during embryogenesis.

PMID- 11526088
TI  - A HOX complex, a repressor element and a 50 bp sequence confer regional
      specificity to a DPP-responsive enhancer.
AB  - A central theme during development and homeostasis is the generation of cell type
      specific responses to the action of a limited number of extant signaling cascades
      triggered by extracellular ligands. The molecular mechanisms by which information
      from such signals are integrated in responding cells in a cell-type specific
      manner remain poorly understood. We have undertaken a detailed characterization
      of an enhancer that is regulated by DPP signaling and by the homeotic protein
      Labial and its partners, Extradenticle and Homothorax. The expression driven by
      this enhancer (lab550) and numerous deletions and point mutants thereof was
      studied in wild-type and mutant Drosophila embryos as well as in cultured cells.
      We find that the lab550 enhancer is composed of two elements, a Homeotic Response
      Element (HOMRE) and a DPP Response Element (DPPRE) that synergize. None of these
      two elements can reproduce the expression of lab550, either with regard to
      expression level or with regard to spatial restriction. The isolated DPPRE of
      lab550 responds extremely weakly to DPP. Interestingly, we found that the
      inducibility of this DPPRE is weak because it is tuned down by the action of a
      repressor element. This repressor element and an additional 50 bp element appear
      to be crucial for the cooperation of the HOMRE and the DPPRE, and might tightly
      link the DPP response to the homeotic input. The cooperation between the
      different elements of the enhancer leads to the segmentally restricted activity
      of lab550 in the endoderm and provides a mechanism to create specific responses
      to DPP signaling with the help of a HOX protein complex.

PMID- 11526089
TI  - CD antigens 2001.

PMID- 11526090
TI  - Molecular mimicry: anti-DNA antibodies may arise inadvertently as a response to
      antibodies generated to microorganisms.
AB  - The origin of anti-DNA antibodies remains speculative. We argue that some of
      these antibodies may arise inadvertently in nature during the course of a normal
      immune response due to their induction by antibodies which bear structures
      (mimotopes) that mimic DNA. These antibodies are not necessarily DNA specific
      but, like the T15 idiotype (id)-positive antibodies which bind to
      phosphorylcholine, are produced normally to some environmental or microbial
      antigen. Such a mimotope was found in a T15(+) antibody at the highly specific
      region encoded principally by the D gene, DFL16.1. This mimotope was also found
      in human antibodies that are encoded by DXP'1, the human counterpart of DFL16.1
      and which is used commonly in anti-DNA antibodies. The mimotope is closely
      related to the epitope responsible for the T15 id and appears to be cryptic or
      normally hidden in the native protein. The existence of such a common, conserved
      sequence raises questions about how easily anti-DNA antibodies can be generated
      in nature and what purpose these proteins may serve. Molecular mimicry with
      regard to autoimmunity must thus be viewed as existing not necessarily between
      the infectious agent and self-antigens, but also between the antibodies induced
      by the organism and the self-antigens.

PMID- 11526091
TI  - Reversal of experimental allergic encephalomyelitis with non-mitogenic, non
      depleting anti-CD3 mAb therapy with a preferential effect on T(h)1 cells that is
      augmented by IL-4.
AB  - This study examined whether therapy with a non-mitogenic, non-activating anti-CD3
      mAb (G4.18) alone, or in combination with the T(h)2 cytokines, could inhibit
      induction or facilitate recovery from experimental allergic encephalomyelitis
      (EAE) in Lewis rats. G4.18, but not rIL-4, rIL-5 or anti-IL-4 mAb, reduced the
      severity and accelerated recovery from active EAE. A combination of rIL-4 with
      G4.18 was more effective than G4.18 alone. The infiltrate of CD4(+) and CD8(+) T
      cells, B cells, dendritic cells, and macrophages in the brain stem was less with
      combined G4.18 and IL-4 than G4.18 therapy or no treatment. Residual cells had
      preferential sparing of T(r)1 cytokines IL-5 and transforming growth factor-beta
      with loss of T(h)1 markers IL-2, IFN-gamma and IL-12Rbeta2, and the T(h)2
      cytokine IL-4 as well as macrophage cytokines IL-10 and tumor necrosis factor
      alpha. Lymph nodes draining the site of immunization had less mRNA for T(h)1
      cytokines, but T(h)2 and T(r)1 cytokine expression was spared. Treatment with
      G4.18, rIL-4 or rIL-5 from the time of immunization had no effect on the course
      of active EAE. MRC OX-81, a mAb that blocks IL-4, delayed onset by 2 days, but
      had no effect on severity of active EAE. G4.18 also inhibited the ability of
      activated T cells from rats with active EAE to transfer passive EAE. This study
      demonstrated that T cell-mediated inflammation was rapidly reversed by a non
      activating anti-CD3 mAb that blocked effector T(h)1 cells, and spared cells
      expressing T(h)2 and T(r)1 cytokines.

PMID- 11526092
TI  - Eukaryotic heat shock proteins as molecular links in innate and adaptive immune
      responses: Hsp60-mediated activation of cytotoxic T cells.
AB  - Heat shock proteins (HSP) like Hsp60, Hsp70 and gp96 act directly on antigen
      presenting cells (APC), e.g. by inducing the secretion of cytokines. Here we
      analyzed the impact of Hsp60 on the antigen-specific activation of CD8(+) T cells
      in a TCR transgenic system. Hsp60 induced low amounts of IFN-gamma in the absence
      of antigenic peptide; however, the release of IFN-gamma is increased by a factor
      of 3-10 following the addition of Hsp60 to purified populations of OT-1
      [ovalbumin (OVA)257-264/H2-K(b)-restricted] T cells and antigen-pulsed peritoneal
      exudate cells (PEC) as APC. This effect is strictly correlated with the PEC
      ability to produce IL-12. In contrast, antigen-specific IL-2 secretion and T cell
      proliferation was not changed in the presence of Hsp60. Hsp60-containing OT-1 T
      cell cultures produced IFN-gamma even when the number of antigenic MHC class I
      complexes was too low to be stimulatory and could not be detected with specific
      mAb. Hsp60, thus, acts as a catalyzing molecule to initiate both innate and
      adaptive immune responses, and its presence (e.g. during an infection with
      cellular destruction) has direct consequences for the activation of otherwise
      'ignorant' antigen-specific T cells.

PMID- 11526093
TI  - Molecular cloning and functional characterization of guinea pig IL-12.
AB  - IL-12 is a heterodimeric cytokine that plays a central role in cell-mediated
      immunity. We cloned complete cDNAs of guinea pig homologues of IL-12 p35 and p40
      subunits, and compared their functional properties with human IL-12. Both p35 and
      p40 mRNA were constitutively expressed in the testis and peritoneal macrophages.
      On immunoblotting, anti-guinea pig p40 antibody detected the constitutive
      expression of p40 protein in the testis, while in macrophages it was induced in
      response to lipopolysaccharide. An unidentified 200-kDa macromolecule was also
      expressed in the testis. All recombinant hybrid heterodimer p70 (guinea pig p70,
      human p70 and two interspecies heterodimers) exerted proliferative activity
      toward concanavalin A-primed guinea pig and human lymphoblasts in a dose
      dependent manner. A similar tendency was observed in IFN-gamma production in IL-2
      treated human lymphocytes. All hybrid heterodimers also induced IFN-gamma mRNA
      from IL-2-treated guinea pig splenocytes. Thus, unlike the current concept that
      the p35 subunit determines the species incompatibility of IL-12 in humans and
      mice, p35 has marginal ability to define its species-specific functional
      expression between humans and guinea pigs. In addition, constitutive expression
      of IL-12 or related molecules in the testis indicated a potential role of this
      molecule in regulation of physiological or pathophysiological conditions in the
      reproductive system.

PMID- 11526094
TI  - Quantitative analysis of phospholipids and gangliosides in bone marrow
      progenitors of lymphocytes, thymocytes and mature lymphocytes in tumor-bearing
      animals.
AB  - The phospholipid and ganglioside composition in bone marrow progenitors of
      lymphocytes, thymocytes and mature lymphocytes of intact rats and rats with
      sarcoma 45 were studied. The lymphocytes and their progenitors were isolated by
      Ficoll-Paque density centrifugation. The phospholipids and gangliosides were
      separated by thin-layer chromatography following standard chloroform:methanol
      extraction from the cells. Alterations in the lipid spectrum (both phospholipids
      and gangliosides) were shown to take place during lymphocyte differentiation. The
      rate of ganglioside sialylation diminished, which was expressed as an increase in
      mono- and di-, and a decrease in tri- and tetrasialoganglioside levels. Tumor
      induced alterations in lymphocyte lipid composition involve all stages of
      lymphocyte differentiation. These shifts are believed to be connected with a
      disturbance of the antineoplastic function of lymphocytes and, consequently, the
      immune response of the tumor-bearing organism.

PMID- 11526095
TI  - Transforming growth factor-beta produced by progressor tumors inhibits, while IL
      10 produced by regressor tumors enhances, Langerhans cell migration from skin.
AB  - The induction of epidermal immunity depends on activation of local dendritic
      cells (DC), Langerhans cells (LC), to migrate from the skin to local lymph nodes
      and mature into potent immunostimulatory cells. We have previously shown that
      progressor skin tumors, which evade immunological destruction, prevent contact
      sensitizer-induced LC migration from the skin to draining lymph nodes. In
      contrast, regressor tumors, which evoke protective immunity, did not inhibit DC
      mobilization. In this study we utilized the skin explant model to determine the
      factors produced by skin tumors which regulate LC migration from the skin.
      Supernatants from two progressor squamous cell carcinoma lines both inhibited LC
      migration, whereas supernatants from two regressor squamous cell carcinoma lines
      both enhanced LC mobilization. Transforming growth factor (TGF)-beta1 inhibited,
      while IL-10 enhanced, LC migration from cultured skin. Both reduced the ability
      of LC to mature into potent allostimulators. Antibody neutralization identified
      that TGF-beta1 produced by the progressor tumor was responsible for inhibition of
      LC migration, while IL-10 produced by the regressor tumor enhanced LC
      mobilization. Thus these studies show that skin tumors influence DC mobilization
      from tumors by production of cytokines, and that TGF-beta1 is one factor produced
      by tumors which can immobilize LC and keep them in an immature form. This is
      likely to be an important mechanism of tumor escape from the immune system as
      progressor tumors inhibited, while regressor tumors enhanced DC mobilization.

PMID- 11526096
TI  - Murine models of systemic lupus erythematosus: B and T cell responses to
      spliceosomal ribonucleoproteins in MRL/Fas(lpr) and (NZB x NZW)F(1) lupus mice.
AB  - (NZB x NZW)F(1) and MRL/Fas(lpr) lupus mice present a similar phenotype with a
      spectrum of autoantibodies associated with very severe nephritis. It is thought,
      however, that in contrast to other lupus-prone mice such as MRL/Fas(lpr) mice,
      (NZB x NZW)F(1) mice do not generate autoantibodies to ribonucleoproteins (RNP)
      Sm/RNP. In this study, we demonstrate that contrary to previous reports, the
      autoimmune response directed against Sm/RNP antigens also occurs in NZB x NZW
      mice. CD4(+) T cells from unprimed 10-week-old NZB x NZW mice proliferate and
      secrete IL-2 in response to peptide 131-151 of the U1-70K protein, which is known
      to contain a T(h) epitope recognized by CD4(+) T cells from MRL/Fas(lpr) mice.
      Peptide 131-151, which was found to bind I-A(k) and I-E(k) class II MHC
      molecules, also bound both I-A(d) and I-E(d) molecules. This result led us to
      also re-evaluate longitudinally the anti-Sm/RNP antibody response in NZB x NZW
      mice. We found that 25-week-old mice do produce antibodies reacting with several
      small nuclear and heterogeneous nuclear (hn) RNP proteins, such as SmD1, U1-70K
      and hnRNP A2/B1 proteins. The fine specificity of these antibodies was studied
      with overlapping synthetic peptides. The same antigenically positive and negative
      peptides were characterized in MRL/Fas(lpr) and NZB x NZW mice in the three
      proteins. This new finding can help to understand the mechanisms involved in the
      development of the anti-Sm/RNP antibody response and, particularly, the role
      played by non-MHC genes in this autoimmune response.

PMID- 11526097
TI  - In situ demonstration of intraepithelial lymphocyte adhesion to villus
      microvessels of the small intestine.
AB  - The recirculation of lymphocytes through the intestinal mucosa is important for
      specific immune defense, but the origin and differentiation of intraepithelial
      lymphocytes (IEL) are not fully understood. The present study therefore used
      intravital microscopy to investigate the migration of IEL to the villus mucosa
      and Peyer's patches of the small intestine. IEL were separated from inverted
      murine small intestine and mesenteric lymph node (MLN) T cells were also
      isolated. The adhesion of fluorescence-labeled lymphocytes to postcapillary
      venules (PCV) of Peyer's patches and arcade microvessels of small intestinal
      villi was observed after injection. In some experiments, the effect of antibodies
      against adhesion molecules on cell kinetics were investigated. IEL time
      dependently accumulated in villus microvessels of the small intestine, whereas
      few MLN cells did. Few IEL adhered to the PCV of Peyer's patches. IEL were shown
      to express alpha(E)beta(7)-integrin but not L-selectin. The accumulation of IEL
      in villus archade was significantly inhibited by antibody against beta(7)
      integrin or mucosal addressin cell adhesion molecules (MAdCAM)-1, but not by
      alpha(E)-integrin. The combined blocking of beta(7)-integrin and MAdCAM-1 further
      attenuated the sticking of IEL in this area, although it did not entirely block
      the IEL adherence. The adherence of CD4(+) or TCRalphabeta IEL to villus
      microvessels was significantly greater than that of CD4(-) or TCRgammadelta IEL.
      It was demonstrated in situ for the first time that IEL adhered selectively to
      the villus microvessels of the small intestine partly via beta(7) and MAdCAM-1.

PMID- 11526098
TI  - Clonal instability of V region hypermutation in the Ramos Burkitt's lymphoma cell
      line.
AB  - Affinity maturation of the humoral immune response is caused by single base
      changes that are introduced into the V regions of the Ig genes during a brief
      period of B cell differentiation. It has recently become possible to study V
      region mutation in some human Burkitt's lymphoma cell lines that mutate their V
      regions and express surface markers that suggest they arose from the malignant
      transformation of germinal center B cells. Ramos Burkitt's cells constitutively
      mutate their V regions at a rate of approximately 2 x 10(-5)
      mutations/bp/generation. However, the sequencing of unselected V regions
      suggested that our Ramos cell line was progressively losing its ability to
      undergo V region hypermutation. To accurately quantify this process, subclones
      with different nonsense mutations in the mu heavy chain V region were identified.
      Reversion analysis and sequencing of unselected V regions were used to examine
      the clonal stability of V region hypermutation. Even after only 1 month in
      culture, stable and unstable subclones could be identified. The identification of
      mutating and non-mutating subclones of Ramos provided a unique opportunity to
      identify factors involved in the mutational process. Differential gene expression
      between mutating and non-mutating Ramos clones was examined by RT-PCR and cDNA
      microarray analyses. We found that the expression of activation-induced cytidine
      deaminase (AID), a putative cytidine deaminase, correlated with mutation rates in
      Ramos subclones. These results suggest that the hypermutation phenotype is
      inherently unstable in Ramos and that long culture periods favor outgrowth of non
      mutating cells that express lower levels of AID.

PMID- 11526099
TI  - Distinct requirements for IL-6 in polyclonal and specific Ig production induced
      by microorganisms.
AB  - The role of IL-6 in Ig production induced in the mouse by lactate dehydrogenase
      elevating virus (LDV), Toxoplasma gondii or lipopolysaccharide (LPS) was
      assessed. Following infection with LDV, a strong activator of B cells, an early
      and transient IL-6 production was observed, that originated predominantly from
      macrophages. Whereas LDV-induced B lymphocyte proliferation appeared independent
      of IL-6, mice deficient for this cytokine showed a marked reduction in their
      total T-dependent IgG2a production when compared to their normal counterparts. By
      contrast, specific responses directed against either LDV or non-viral antigens
      administered at the time of infection were not decreased in the absence of IL-6.
      Similarly, polyclonal, but not anti-parasite IgG2a production triggered by T.
      gondii infection was strongly dependent on the presence of IL-6. Finally, T
      independent total IgG3 secretion triggered by LPS was also markedly reduced in IL
      6-deficient mice. These results suggest that IL-6 plays a major role in T
      dependent and T-independent polyclonal Ig production following B lymphocyte
      activation by viruses, and parasites, but not in specific antibody responses
      induced by the same microorganisms.

PMID- 11526100
TI  - Mouse B-1 cell-derived mononuclear phagocyte, a novel cellular component of acute
      non-specific inflammatory exudate.
AB  - At least three B cell subsets, B-1a, B-1b and B-2, or conventional B cells are
      present in the mouse periphery. Here we demonstrate that B-1 cells spontaneously
      proliferate in stationary cultures of normal adherent mouse peritoneal cells. B-1
      cells were characterized by morphology, immunohistochemistry and flow cytometry.
      IgM was detected in the supernatants of these cultures. We demonstrated that the
      major cell population analyzed expresses the B-1b phenotype. When these cells
      were transferred to a new culture, a large proportion of them adhere to the
      plastic surface, and spread as bipolar cells endowed with the capacity to
      phagocytose via Fc and mannose receptors. Flow cytometry analysis of these
      adherent cells demonstrated that the great majority of them share both B-220 and
      Mac-1 antigens. Nevertheless, 45% of them were exclusively Mac-1(+). Finally,
      when they were labeled in vitro with [(3)H]thymidine and transferred to the
      peritoneal cavity of naive mice, they migrate to a non-specific inflammatory
      focus induced by a foreign-body implant. These data demonstrate that B-1 cells,
      mainly B-1b cells, not only proliferate and differentiate into a mononuclear
      phagocyte in vitro, but also that they exit the peritoneal cavity and migrate to
      a non-specific inflammatory milieu.

PMID- 11526101
TI  - Two distinct steps of immigration of hematopoietic progenitors into the early
      thymus anlage.
AB  - Thymic epithelial cells, which create a three-dimensionally organized meshwork
      structure peculiar to the thymus, develop from simple epithelia of the third
      pharyngeal pouch and cleft during organogenesis. We comparatively investigated
      the thymus anlages of normal and nude mice by immunohistochemical analysis with
      regard to epithelial organization and distribution of hematopoietic progenitor
      cells at early stages of organogenesis. Our results show that development of the
      mouse thymus anlage at early stages can be subdivided into at least two stages by
      the differences in epithelial organization, i.e. stratified epithelial stage on
      embryonic day (Ed) 11 and clustered epithelial stage on Ed12. At the former
      stage, hematopoietic progenitor cells are accumulated in the mesenchymal layer of
      the thymus anlage, and at the latter stage progenitor cells enter the epithelial
      cluster and proliferate. In nude mice, hematopoietic progenitor cells are found
      in the mesenchymal layer on Ed11.5, but they are not observed among epithelial
      cells on Ed12, even though epithelial cells form a cluster structure. The present
      results suggest that aberrant development of the nude mouse thymus anlage occurs
      at the clustered epithelial stage and that epithelial cells of the nude anlage
      lack the ability to induce the entrance of hematopoietic progenitor cells into
      the epithelial cluster.

PMID- 11526102
TI  - Kinetic analysis of the conjugation of ubiquitin to picornavirus 3C proteases
      catalyzed by the mammalian ubiquitin-protein ligase E3alpha.
AB  - The 3C proteases of the encephalomyocarditis virus and the hepatitis A virus are
      both type III substrates for the mammalian ubiquitin-protein ligase E3alpha. The
      conjugation of ubiquitin to these proteins requires internal ten-amino acid-long
      protein destruction signal sequences. To evaluate how these destruction signals
      modulate interactions that must occur between E3alpha and the 3C proteases, we
      have kinetically analyzed the formation of ubiquitin-3C protease conjugates in a
      reconstituted system of purified E1, HsUbc2b/E2(14Kb), and human E3alpha. Our
      measurements show that the encephalomyocarditis virus 3C protease is
      ubiquitinated in this system with K(m) = 42 +/- 11 microm and V(max) = 0.051 +/-
      0.01 pmol/min whereas the parameters for the ubiquitination of the hepatitis A
      virus 3C protease are K(m) = 20 +/- 5 microm and V(max) = 0.018 +/- 0.003
      pmol/min. Mutations in the destruction signal sequences resulted in changes in
      the rate at which E3alpha conjugates ubiquitin to the altered 3C protease
      proteins. The K(m) and V(max) values for these reactions change proportionally in
      the same direction. These results suggest differences in rates of conjugation of
      ubiquitin to 3C proteases are primarily a k(cat) effect. Replacing specific
      encephalomyocarditis virus 3C protease lysine residues with arginine residues was
      found to increase, rather than decrease, the rate of ubiquitin conjugation, and
      the K(m) and V(max) values for these reactions are both higher than for the wild
      type protein. The ability of E3alpha to catalyze the conjugation of ubiquitin to
      both 3C proteases was found to be inhibited by lysylalanine and
      phenylalanylalanine, demonstrating that the same sites on E3alpha that bind
      destabilizing N-terminal amino acids in type I and II substrates also interact
      with the 3C proteases.

PMID- 11526103
TI  - Interaction of the SH2 domain of Fyn with a cytoskeletal protein, beta-adducin.
AB  - Fyn is a Src family tyrosine kinase expressed abundantly in neurons and believed
      to have specific functions in the brain. To understand the function of Fyn
      tyrosine kinase, we attempted to identify Fyn Src homology 2 (SH2) domain-binding
      proteins from a Nonidet P-40-insoluble fraction of the mouse brain. beta-Adducin,
      an actin filament-associated cytoskeletal protein, was isolated by two
      dimensional gel electrophoresis and identified by tandem mass spectrometry. beta
      Adducin was tyrosine phosphorylated by coexpression with wild type but not with a
      kinase-negative form of Fyn in COS-7 cells. Cell staining analysis showed that
      coexpression of beta-adducin with Fyn induced translocation of beta-adducin from
      the cytoplasm to the periphery of the cells where it was colocalized with actin
      filaments and Fyn. These findings suggest that tyrosine-phosphorylated beta
      adducin associates with the SH2 domain of Fyn and colocalizes under plasma
      membranes.

PMID- 11526104
TI  - Elevation of beta-amyloid peptide 2-42 in sporadic and familial Alzheimer's
      disease and its generation in PS1 knockout cells.
AB  - Urea-based beta-amyloid (Abeta) SDS-polyacrylamide gel electrophoresis and
      immunoblots were used to analyze the generation of Abeta peptides in conditioned
      medium from primary mouse neurons and a neuroglioma cell line, as well as in
      human cerebrospinal fluid. A comparable and highly conserved pattern of Abeta
      peptides, namely, 1-40/42 and carboxyl-terminal-truncated 1-37, 1-38, and 1-39,
      was found. Besides Abeta1-42, we also observed a consistent elevation of amino
      terminal-truncated Abeta2-42 in a detergent-soluble pool in brains of subjects
      with Alzheimer's disease. Abeta2-42 was also specifically elevated in
      cerebrospinal fluid samples of Alzheimer's disease patients. To decipher the
      contribution of potential different gamma-secretases (presenilins (PSs)) in
      generating the amino-terminal- and carboxyl-terminal-truncated Abeta peptides, we
      overexpressed beta-amyloid precursor protein (APP)-trafficking mutants in PS1+/+
      and PS1-/- neurons. As compared with APP-WT (primary neurons from control or PS1
      deficient mice infected with Semliki Forest virus), PS1-/- neurons and PS1+/+
      neurons overexpressing APP-Deltact (a slow-internalizing mutant) show a decrease
      of all secreted Abeta peptide species, as expected, because this mutant is
      processed mainly by alpha-secretase. This drop is even more pronounced for the
      APP-KK construct (APP mutant carrying an endoplasmic reticulum retention motif).
      Surprisingly, Abeta2-42 is significantly less affected in PS1-/- neurons and in
      neurons transfected with the endocytosis-deficient APP-Deltact construct. Our
      data confirm that PS1 is closely involved in the production of Abeta1-40/42 and
      the carboxyl-terminal-truncated Abeta1-37, Abeta1-38, and Abeta1-39, but the
      amino-terminal-truncated and carboxyl-terminal-elongated Abeta2-42 seems to be
      less affected by PS1 deficiency. Moreover, our results indicate that the latter
      Abeta peptide species could be generated by a beta(Asp/Ala)-secretase activity.

PMID- 11526105
TI  - Aspartate residues of the Glu-Glu-Asp-Asp (EEDD) pore locus control selectivity
      and permeation of the T-type Ca(2+) channel alpha(1G).
AB  - The structural determinant of the permeation and selectivity properties of high
      voltage-activated (HVA) Ca(2+) channels is a locus formed by four glutamate
      residues (EEEE), one in each P-region of the domains I-IV of the alpha(1)
      subunit. We tested whether the divergent aspartate residues of the EEDD locus of
      low voltage-activated (LVA or T-type) Ca(2+) channels account for the distinctive
      permeation and selectivity features of these channels. Using the whole-cell patch
      clamp technique in the HEK293 expression system, we studied the properties of the
      alpha(1G) T-type, the alpha(1C) L-type Ca(2+) channel subunits, and alpha(1G)
      pore mutants, containing aspartate-to-glutamate conversions in domain III, domain
      IV, or both. Three characteristic features of HVA Ca(2+) channel permeation, i.e.
      (a) Ba(2+) over Ca(2+) permeability, (b) Ca(2+)/Ba(2+) anomalous mole fraction
      effect (AMFE), and (c) high Cd(2+) sensitivity, were conferred on the domain III
      mutant (EEED) of alpha(1G). In contrast, the relative Ca(2+)/Ba(2+) permeability
      and the lack of AMFE of the alpha(1G) wild type channel were retained in the
      domain IV mutant (EEDE). The double mutant (EEEE) displayed AMFE and a Cd(2+)
      sensitivity similar to that of alpha(1C), but currents were larger in Ca(2+)-
      than in Ba(2+)-containing solutions. The mutation in domain III, but not that in
      domain IV, consistently displayed outward fluxes of monovalent cations. H(+)
      blocked Ca(2+) currents in all mutants more efficiently than in alpha(1G). In
      addition, activation curves of all mutants were displaced to more positive
      voltages and had a larger slope factor than in alpha(1G) wild type. We conclude
      that the aspartate residues of the EEDD locus of the alpha(1G) Ca(2+) channel
      subunit not only control its permeation properties, but also affect its
      activation curve. The mutation of both divergent aspartates only partially
      confers HVA channel permeation properties to the alpha(1G) Ca(2+) channel
      subunit.

PMID- 11526106
TI  - Interaction of neuronal calcium sensor-1 (NCS-1) with phosphatidylinositol 4
      kinase beta stimulates lipid kinase activity and affects membrane trafficking in
      COS-7 cells.
AB  - Phosphatidylinositol 4-kinases (PI4K) catalyze the first step in the synthesis of
      phosphatidylinositol 4,5-bisphosphate, an important lipid regulator of several
      cellular functions. Here we show that the Ca(2+)-binding protein, neuronal
      calcium sensor-1 (NCS-1), can physically associate with the type III PI4Kbeta
      with functional consequences affecting the kinase. Recombinant PI4Kbeta, but not
      its glutathione S-transferase-fused form, showed enhanced PI kinase activity when
      incubated with recombinant NCS-1, but only if the latter was myristoylated.
      Similarly, in vitro translated NCS-1, but not its myristoylation-defective
      mutant, was found associated with recombinant- or in vitro translated PI4Kbeta in
      PI4Kbeta-immunoprecipitates. When expressed in COS-7 cells, PI4Kbeta and NCS-1
      formed a complex that could be immunoprecipitated with antibodies against either
      proteins, and PI 4-kinase activity was present in anti-NCS-1 immunoprecipitates.
      Expressed NCS-1-YFP showed co-localization with endogenous PI4Kbeta primarily in
      the Golgi, but it was also present in the walls of numerous large perinuclear
      vesicles. Co-expression of a catalytically inactive PI4Kbeta inhibited the
      development of this vesicular phenotype. Transfection of PI4Kbeta and NCS-1 had
      no effect on basal PIP synthesis in permeabilized COS-7 cells, but it increased
      the wortmannin-sensitive [(32)P]phosphate incorporation into phosphatidylinositol
      4-phosphate during Ca(2+)-induced phospholipase C activation. These results
      together indicate that NCS-1 is able to interact with PI4Kbeta also in mammalian
      cells and may play a role in the regulation of this enzyme in specific cellular
      compartments affecting vesicular trafficking.

PMID- 11526107
TI  - A second exon splicing silencer within human immunodeficiency virus type 1 tat
      exon 2 represses splicing of Tat mRNA and binds protein hnRNP H.
AB  - An equilibrium between spliced and unspliced primary transcripts is essential for
      retrovirus multiplication. This equilibrium is maintained by the presence of
      inefficient splice sites. The A3 3'-splice site of human immunodeficiency virus
      type I (HIV-1) is required for Tat mRNA production. The infrequent utilization of
      this splice site has been attributed to the presence of a suboptimal
      polypyrimidine tract and an exonic splicing silencer (ESS2) in tat exon 2
      approximately 60 nucleotides downstream of 3'-splice site A3. Here, using site
      directed mutagenesis followed by analysis of splicing in vitro and in HeLa cells,
      we show that the 5' extremity of tat exon 2 contains a second exonic splicing
      silencer (ESS2p), which acts to repress splice site A3. The inhibitory property
      of this exonic silencer was active when inserted downstream of another HIV-1 3'
      splice site (A2). Protein hnRNP H binds to this inhibitory element, and two U-to
      C substitutions within the ESS2p element cause a decreased hnRNP H affinity with
      a concomitant increase in splicing efficiency at 3'-splice site A3. This suggests
      that hnRNP H is directly involved in splicing inhibition. We propose that hnRNP H
      binds to the HIV-1 ESS2p element and competes with U2AF(35) for binding to the
      exon sequence flanking 3'-splice site A3. This binding results in the inhibition
      of splicing at 3'-splice site A3.

PMID- 11526108
TI  - The Drosophila nitric-oxide synthase gene (dNOS) encodes a family of proteins
      that can modulate NOS activity by acting as dominant negative regulators.
AB  - Nitric oxide (NO) is involved in organ development, synaptogenesis, and response
      to hypoxia in Drosophila. We cloned and analyzed the only gene in the fly genome
      that encodes Drosophila nitric-oxide synthase (dNOS). It consists of 19 exons and
      is dispersed over 34 kilobases of genomic DNA. Alternative transcription start
      sites and alternative splice sites are used to generate a remarkable variety of
      mRNAs from the dNOS gene. We identified eight new transcripts that are widely
      expressed throughout Drosophila development and encode a family of DNOS-related
      proteins. Alternative splicing affects both the 5'-untranslated region and the
      coding region of the dNOS primary transcript. Most of the splicing alterations in
      the coding region of the gene lead to premature termination of the open reading
      frame. As a result, none of the alternative transcripts encode an enzymatically
      active protein. However, some of these shorter DNOS protein products can
      effectively inhibit enzymatic activity of the full-length DNOS1 protein when co
      expressed in mammalian cells, thus acting as dominant negative regulators of NO
      synthesis. Using immunoprecipitation, we demonstrate that these short DNOS
      protein isoforms can form heterodimers with DNOS1, pointing to a physical basis
      for the dominant negative effect. Our results suggest a novel regulatory function
      for the family of proteins encoded by the Drosophila NOS gene.

PMID- 11526109
TI  - Insulin receptor substrate-1 pleckstrin homology and phosphotyrosine-binding
      domains are both involved in plasma membrane targeting.
AB  - The localization of insulin receptor substrate (IRS) molecules may be responsible
      for the differential biological activities of insulin and other peptides such as
      platelet-derived growth factor. The subcellular localization of IRS-1 is
      controversial, with some reports suggesting association with the cytoskeleton and
      other studies reporting membrane localization. In this study, we used
      immunofluorescence microscopy to define the localization of IRS-1. In the basal
      state, recombinant IRS-1 was localized predominantly in the cytoplasm. In
      response to insulin, recombinant IRS-1 translocated to the plasma membrane. We
      have also studied the localization of green fluorescent protein (GFP) fusion
      proteins. Unlike native IRS-1, a fusion protein containing GFP plus full-length
      IRS-1 appeared to localize in inclusion bodies. In contrast, when GFP was fused
      to the N terminus of IRS-1 (i.e. the pleckstrin homology and phosphotyrosine
      binding domains), this fusion protein was targeted to the plasma membrane.
      Mutations of phosphoinositide-binding sites in both the pleckstrin homology and
      phosphotyrosine-binding domains significantly reduced the ability of Myc-tagged
      IRS-1 to translocate to the plasma membrane following insulin stimulation.
      However, these mutations did not cause a statistically significant impairment of
      tyrosine phosphorylation in response to insulin. This raises the possibility that
      IRS-1 tyrosine phosphorylation may occur prior to plasma membrane translocation.

PMID- 11526111
TI  - Alteration of product specificity of Rhodobacter sphaeroides phytoene desaturase
      by directed evolution.
AB  - Phytoene desaturases occurring in nature convert phytoene to either neurosporene
      or lycopene in most eubacteria. Approximately 10% of known phytoene desaturases,
      as in Rhodobacter, produce neurosporene, whereas the rest produce lycopene. These
      two types of enzymes, although similar in function, have relatively low
      similarity (below 60%) in terms of nucleotide or amino acid sequence. The
      mechanism controlling the product specificity of these enzymes is unclear. Here
      we used directed evolution to change the product of Rhodobacter sphaeroides
      phytoene desaturase (crtI gene product), a neurosporene-producing enzyme, to
      lycopene. Two generations of random mutagenesis were performed, from which three
      positive mutants were isolated and sequenced. We then used site-directed
      mutagenesis to determine the effect of each amino acid change. Gathering
      information from random mutagenesis, we further recombined the beneficial
      mutations by site-directed mutagenesis and increased the percent of lycopene
      production to 90%.

PMID- 11526110
TI  - FYVE domain targets Pib1p ubiquitin ligase to endosome and vacuolar membranes.
AB  - Signaling by phosphatidylinositol 3-kinases (PI3Ks) is often mediated by proteins
      which bind PI3K products directly and are localized to intracellular membranes
      rich in PI3K products. The FYVE finger domain binds with high specificity to
      PtdIns3P and proteins containing this domain have been shown to be important
      components of diverse PI3K signaling pathways. The genome of the yeast
      Saccharomyces cerevisiae encodes five proteins containing FYVE domains, including
      Pib1p, whose function is unknown. In addition to a FYVE finger motif, the primary
      structure of Pib1p contains a region rich in cysteine and histidine residues that
      we demonstrate binds 2 mol eq of zinc, consistent with this region containing a
      RING structural domain. The Pib1p RING domain exhibited E2-dependent ubiquitin
      ligase activity in vitro, indicating that Pib1p is an E3 RING-type ubiquitin
      ligase. Fluorescence microscopy was used to demonstrate that a GFP-Pib1p fusion
      protein localized to endosomal and vacuolar membranes and deletional analysis of
      Pib1p domains indicated that localization of GFP-Pib1p is mediated solely by the
      FYVE domain. These results suggest that Pib1p mediates ubiquitination of a subset
      of cellular proteins localized to endosome and vacuolar membranes, and they
      expand the repertoire of PI3K-regulated pathways identified in eukaryotic cells.

PMID- 11526112
TI  - Activation of the Ras-cAMP signal transduction pathway inhibits the proteasome
      independent degradation of misfolded protein aggregates in the endoplasmic
      reticulum lumen.
AB  - Many kinds of misfolded secretory proteins are known to be degraded in the
      endoplasmic reticulum (ER). Dislocation of misfolded proteins from the ER to the
      cytosol and subsequent degradation by the proteasome have been demonstrated.
      Using the yeast Saccharomyces cerevisiae, we have been studying the secretion of
      a heterologous protein, Rhizopus niveus aspartic proteinase-I (RNAP-I).
      Previously, we found that the pro sequence of RNAP-I is important for the folding
      and secretion, and that Deltapro, a mutated derivative of RNAP-I in which the
      entire region of the pro sequence is deleted, forms gross aggregates in the yeast
      ER. In this study, we show that the degradation of Deltapro occurs independently
      of the proteasome. Its degradation was not inhibited either by a potent
      proteasome inhibitor or in a proteasome mutant. We also show that neither the
      export from the ER nor the vacuolar proteinase is required for the degradation of
      Deltapro. These results raise the possibility that the Deltapro aggregates are
      degraded in the ER lumen. We have isolated a yeast mutant in which the
      degradation of Deltapro is delayed. We show that the mutated gene is IRA2, which
      encodes a GTPase-activating protein for Ras. Because Ira2 protein is a negative
      regulator of the Ras-cAMP pathway, this result suggests that hyperactivation of
      the Ras-cAMP pathway inhibits the degradation of Deltapro. Consistently, down
      regulation of the Ras-cAMP pathway in the ira2 mutant suppressed the defect of
      the degradation of Deltapro. Thus, the Ras-cAMP signal transduction pathway seems
      to control the proteasome-independent degradation of the ER misfolded protein
      aggregates.

PMID- 11526113
TI  - The loss of cytoplasmic potassium upon host cell breakdown triggers egress of
      Toxoplasma gondii.
AB  - The ability of intracellular parasites to monitor the viability of their host
      cells is essential for their survival. The protozoan parasite Toxoplasma gondii
      actively invades nucleated animal cells and replicates in their cytoplasm. Two to
      3 days after infection, the parasite-filled host cell breaks down and the
      parasites leave to initiate infection of a new cell. Parasite egress from the
      host cell is triggered by rupture of the host plasma membrane and the ensuing
      reduction in the concentration of cytoplasmic potassium. The many other changes
      in host cell composition do not appear be used as triggers. The reduction in the
      host cell [K(+)] appears to activate a phospholipase C activity in Toxoplasma
      that, in turn, causes an increase in cytoplasmic [Ca(2+)] in the parasite. The
      latter appears to be necessary and sufficient for inducing egress, as buffering
      of cytoplasmic Ca(2+) blocks egress and calcium ionophores circumvent the need
      for a reduction of host cell [K(+)] and parasite phospholipase C activation. The
      increase in [Ca(2+)](C) brings about egress by the activation of at least two
      signaling pathways: the protein kinase TgCDPK1 and the calmodulin-dependent
      protein phosphatase calcineurin.

PMID- 11526114
TI  - BRCA1 RING domain cancer-predisposing mutations. Structural consequences and
      effects on protein-protein interactions.
AB  - Cancer-predisposing missense mutations in the RING domain of BRCA1 primarily
      target Zn(2+)-liganding residues. Here we report on the structural consequences
      of such mutations introduced into the second Zn(2+) site (Site II) of the BRCA1
      RING domain and their effect on the interaction with the BARD1 RING domain. Each
      of the BRCA1 Site II mutants still interact and form a stable heterodimer with
      BARD1. Limited proteolysis of BRCA1/BARD1 complexes, monitored by matrix-assisted
      laser desorption ionization time-of-flight spectrometry, show that the mutations
      cause a local structural perturbation that is primarily confined to the second
      Zn(2+) binding loop of the BRCA1 subunit. These findings are consistent with the
      structure of the BRCA1/BARD1 heterodimer, which shows this region is well removed
      from the helices required for dimerization with BARD1. Instead, the mutations
      alter a region of BRCA1 that appears to be required for interaction with
      ubiquitin-conjugating enzymes.

PMID- 11526115
TI  - The Rieske Fe/S protein of the cytochrome b6/f complex in chloroplasts: missing
      link in the evolution of protein transport pathways in chloroplasts?
AB  - The Rieske Fe/S protein, a nuclear-encoded subunit of the cytochrome b(6)/f
      complex in chloroplasts, is retarded in the stromal space after import into the
      chloroplast and only slowly translocated further into the thylakoid membrane
      system. As shown by the sensitivity to nigericin and to specific competitor
      proteins, thylakoid transport takes place by the DeltapH-dependent TAT pathway.
      The Rieske protein is an untypical TAT substrate, however. It is only the second
      integral membrane protein shown to utilize this pathway, and it is the first
      authentic substrate without a cleavable signal peptide. Transport is instead
      mediated by the NH(2)-terminal membrane anchor, which lacks, however, the twin
      arginine motif indicative of DeltapH/TAT-dependent transport signals.
      Furthermore, transport is affected by sodium azide as well as by competitor
      proteins for the Sec pathway in chloroplasts, demonstrating for the first time
      some cross-talk of the two pathways. This might take place in the stroma where
      the Rieske protein accumulates after import in several complexes of high
      molecular mass, among which the cpn60 complex is the most prominent. These
      untypical features suggest that the Rieske protein represents an intermediate or
      early state in the evolution of the thylakoidal protein transport pathways.

PMID- 11526116
TI  - Toxicity of antiviral nucleoside analogs and the human mitochondrial DNA
      polymerase.
AB  - To examine the role of the mitochondrial polymerase (Pol gamma) in clinically
      observed toxicity of nucleoside analogs used to treat AIDS, we examined the
      kinetics of incorporation catalyzed by Pol gamma for each Food and Drug
      Administration-approved analog plus 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)
      5-iodouracil (FIAU), beta-L-(-)-2',3'-dideoxy-3'-thiacytidine (-)3TC, and (R)-9
      (2-phosphonylmethoxypropyl)adenine (PMPA). We used recombinant exonuclease
      deficient (E200A), reconstituted human Pol gamma holoenzyme in single turnover
      kinetic studies to measure K(d) (K(m)) and k(pol) (k(cat)) to estimate the
      specificity constant (k(cat)/K(m)) for each nucleoside analog triphosphate. The
      specificity constants vary more than 500,000-fold for the series ddC > ddA (ddI)
      > 2',3'-didehydro-2',3'-dideoxythymidine (d4T) >> (+)3TC >> (-)3TC > PMPA >
      azidothymidine (AZT) >> Carbovir (CBV). Abacavir (prodrug of CBV) and PMPA are
      two new drugs that are expected to be least toxic. Notably, the higher toxicities
      of d4T, ddC, and ddA arose from their 13-36-fold tighter binding relative to the
      normal dNTP even though their rates of incorporation were comparable with PMPA
      and AZT. We also examined the rate of exonuclease removal of each analog after
      incorporation. The rates varied from 0.06 to 0.0004 s(-1) for the series FIAU >
      (+)3TC approximately equal to (-)3TC > CBV > AZT > PMPA approximately equal to
      d4T >> ddA (ddI) >> ddC. Removal of ddC was too slow to measure (<0.00002 s(-1)).
      The high toxicity of dideoxy compounds, ddC and ddI (metabolized to ddA), may be
      a combination of high rates of incorporation and ineffective exonuclease removal.
      Conversely, the more effective excision of (-)3TC, CBV, and AZT may contribute to
      lower toxicity. FIAU is readily extended by the next correct base pair (0.13 s(
      1)) faster than it is removed (0.06 s(-1)) and, therefore, is stably incorporated
      and highly mutagenic. We define a toxicity index for chain terminators to account
      for relative rates of incorporation versus removal. These results provide a
      method to rapidly screen new analogs for potential toxicity.

PMID- 11526117
TI  - Heterogeneous processing and zona pellucida binding activity of pig zonadhesin.
AB  - Zonadhesin is a mosaic protein in sperm membrane fractions that binds directly
      and in a species-specific manner to the extracellular matrix (zona pellucida) of
      the oocyte. The active form of pig zonadhesin from capacitated, epididymal
      spermatozoa comprises two covalently associated polypeptide chains of M(r)
      105,000 (p105) and M(r) 45,000 (p45). Here we report detection and
      characterization of multiple zonadhesin isoforms in freshly ejaculated cells.
      Antibodies to the predicted von Willebrand D0-D1, D1, and D3 domains of pig
      zonadhesin recognized p105, p45, and additional M(r) 60,000-90,000 polypeptides
      in particulate fractions of uncapacitated cells. Although the p105/45 form
      constituted a minority of all zonadhesin forms in sperm membrane fractions, it
      was the predominant form capable of binding to the pig zona pellucida. Zonadhesin
      binding sites were distributed over the entire zona pellucida. Anion exchange
      chromatography resolved active, p105/45 zonadhesin from the p60-90 inactive
      forms. Without disulfide bond reduction some zonadhesin was M(r) > or = 300,000,
      including M(r) 300,000 and 900,000 proteins comprising in part multimers of
      p105/45. The multimeric forms did not bind the zona pellucida as avidly as did
      the p105/45 monomer. Expressed D1 and D3 domain fragments containing the
      CG(L/V)CG sequence motif spontaneously formed multimers at -246 mV E(h) in vitro.
      Double Cys --> Ser mutants of the D1 fragment formed multimers with the same
      apparent kinetics as the wild type protein. Zonadhesin localized to the apical
      head of pig spermatozoa. We conclude that a heterogeneous combination of specific
      proteolysis and intermolecular disulfide bond formation in the sperm head
      generates multiple forms of zonadhesin with differing avidities for the zona
      pellucida.

PMID- 11526118
TI  - Two active site asparagines are essential for the reaction mechanism of the class
      III anaerobic ribonucleotide reductase from bacteriophage T4.
AB  - Class III ribonucleotide reductase is an anaerobic enzyme that uses a glycyl
      radical to catalyze the reduction of ribonucleotides to deoxyribonucleotides and
      formate as ultimate reductant. The reaction mechanism of class III ribonucleotide
      reductases requires two cysteines within the active site, Cys-79 and Cys-290 in
      bacteriophage T4 NrdD numbering. Cys-290 is believed to form a transient thiyl
      radical that initiates the reaction with substrate and Cys-79 to take part as a
      transient thiyl radical in later steps of the reductive reaction. The recently
      solved three-dimensional structure of class III ribonucleotide reductase (RNR)
      from bacteriophage T4 shows that two highly conserved asparagines, Asn-78 and Asn
      311, are positioned close to the essential Cys-79. We have investigated the
      function of Asn-78 and Asn-311 by site-directed mutagenesis and measured enzyme
      activity and glycyl radical formation in five single (N78(A/C/D) and N311(A/C))
      and one double (N78A/N311A) mutant proteins. Our results suggest that both
      asparagines are important for the catalytic mechanism of class III RNR and that
      one asparagine can partially compensate for the lack of the other functional
      group in the single Asn --> Ala mutant proteins. A plausible role for these two
      asparagines could be in positioning formate in the active site to orient it
      toward the proposed thiyl radical of Cys-79. This would also control the highly
      reactive carbon dioxide radical anion form of formate within the active site
      before it is released as carbon dioxide. A detailed reaction scheme including the
      function of the two asparagines and two formate molecules is proposed for class
      III RNRs.

PMID- 11526119
TI  - Definitive identification of mammalian 5-hydroxymethyluracil DNA N-glycosylase
      activity as SMUG1.
AB  - Purification from calf thymus of a DNA N-glycosylase activity (HMUDG) that
      released 5-hydroxymethyluracil (5hmUra) from the DNA of Bacillus subtilis phage
      SPO1 was undertaken. Analysis of the most purified fraction by SDS-polyacrylamide
      gel electrophoresis revealed a multiplicity of protein species making it
      impossible to identify HMUDG by inspection. Therefore, we renatured the enzyme
      after SDS-polyacrylamide gel electrophoresis and assayed slices of the gel for
      DNA N-glycosylase activity directed against 5hmUra. Maximum enzymatic activity
      was identified between molecular mass markers 30 and 34 kDa. Protein was
      extracted from gel slices and subjected to tryptic digestion and analysis by mass
      spectrometry. Analysis revealed the presence of 11 peptides that were homologous
      or identical to the sequence of the recently characterized human single-stranded
      monofunctional uracil DNA N-glycosylase (hSMUG1). The cDNA of hSMUG1 was isolated
      and expressed as a recombinant glutathione S-transferase fusion protein that was
      shown to release 5hmUra with 20x the specific activity of the most purified
      bovine fraction. We conclude that hSMUG1 and HMUDG are the same protein.

PMID- 11526120
TI  - Spectroscopic and kinetic characterization of the bifunctional chorismate
      synthase from Neurospora crassa: evidence for a common binding site for 5
      enolpyruvylshikimate 3-phosphate and NADPH.
AB  - Chorismate synthase catalyzes the anti-1,4-elimination of the phosphate group and
      the C-(6proR) hydrogen from 5-enolpyruvylshikimate 3-phosphate to yield
      chorismate, a central building block in aromatic amino acid biosynthesis. The
      enzyme has an absolute requirement for reduced FMN, which in the case of the
      fungal chorismate synthases is supplied by an intrinsic FMN:NADPH oxidoreductase
      activity, i.e. these enzymes have an additional catalytic activity. Therefore,
      these fungal enzymes have been termed "bifunctional." We have cloned chorismate
      synthase from the common bread mold Neurospora crassa, expressed it
      heterologously in Escherichia coli, and purified it in a three-step purification
      procedure to homogeneity. Recombinant N. crassa chorismate synthase has a
      diaphorase activity, i.e. it catalyzes the reduction of oxidized FMN at the
      expense of NADPH. Using NADPH as a reductant, a reduced flavin intermediate was
      observed under single and multiple turnover conditions with spectral features
      similar to those reported for monofunctional chorismate synthases, thus
      demonstrating that the intermediate is common to the chorismate synthase
      catalyzed reaction. Furthermore, multiple turnover experiments in the presence of
      oxygen have provided evidence that NADPH binds in or near the substrate (5
      enolpyruvylshikimate 3-phosphate) binding site, suggesting that NADPH binding to
      bifunctional chorismate synthases is embedded in the general protein structure
      and a special NADPH binding domain is not required to generate the intrinsic
      oxidoreductase activity.

PMID- 11526121
TI  - beta 1-adrenergic receptor association with the synaptic scaffolding protein
      membrane-associated guanylate kinase inverted-2 (MAGI-2). Differential regulation
      of receptor internalization by MAGI-2 and PSD-95.
AB  - The beta1-adrenergic receptor (beta1AR) is known to be localized to synapses and
      to modulate synaptic plasticity in many brain regions, but the molecular
      mechanisms determining beta1AR subcellular localization are not fully understood.
      Using overlay and pull-down techniques, we found that the beta1AR carboxyl
      terminus associates with MAGI-2 (membrane-associated guanylate kinase inverted
      2), a protein also known as S-SCAM (synaptic scaffolding molecule). MAGI-2 is a
      multidomain scaffolding protein that contains nine potential protein-protein
      interaction modules, including 6 PDZ domains, 2 WW domains, and a guanylate
      kinase-like domain. The beta1AR carboxyl terminus binds with high affinity to the
      first PDZ domain of MAGI-2, with the last few amino acids of the beta1AR carboxyl
      terminus being the key determinants of the interaction. In cells, the association
      of full-length beta1AR with MAGI-2 occurs constitutively and is enhanced by
      agonist stimulation of the receptor, as assessed by both co-immunoprecipitation
      experiments and immunofluorescence co-localization studies. Agonist-induced
      internalization of the beta1AR is markedly increased by co-expression with MAGI
      2. Strikingly, this result is the opposite of the effect of co-expression with
      PSD-95, a previously reported binding partner of the beta1AR. Further cellular
      experiments revealed that MAGI-2 has no effect on beta1AR oligomerization but
      does promote association of beta1AR with the cytoplasmic signaling protein beta
      catenin, a known MAGI-2 binding partner. These data reveal that MAGI-2 is a
      specific beta1AR binding partner that modulates beta1AR function and facilitates
      the physical association of the beta1AR with intracellular proteins involved in
      signal transduction and synaptic regulation.

PMID- 11526122
TI  - Nkx2-5 activity is essential for cardiomyogenesis.
AB  - The homeobox transcription factor tinman is essential for heart vessel formation
      in Drosophila. In contrast, mice lacking the murine homologue Nkx2-5 are
      defective in cardiac looping but not in cardiac myocyte development. The lack of
      an essential role for Nkx2-5 in cardiomyogenesis in mammalian systems is most
      likely the result of genetic redundancy with family members. In this study, we
      used a dominant negative mutant of Nkx2-5, created by fusing the repressor domain
      of engrailed 2 to the Nkx2-5 homeodomain, termed Nkx/EnR. Expression of Nkx/EnR
      inhibited Me(2)SO-induced cardiomyogenesis in P19 cells but not skeletal
      myogenesis. Nkx/EnR inhibited expression of cardiomyoblast markers, such as GATA
      4 and MEF2C, but not of mesoderm markers, such as Brachyury T and Wnt5b, or of
      skeletal lineage markers, such as MyoD and Mox1. To identify the minimal region
      of Nkx2-5 that can trigger cardiomyogenesis, we analyzed the activity of various
      Nkx2-5 deletion mutants. The C-terminal domain was not necessary for the ability
      of Nkx2-5 to induce cardiomyogenesis and loss of this domain did not enhance
      myogenesis. Therefore, Nkx2-5 function is essential for commitment of mesoderm
      into the cardiac muscle lineage, and the N-terminal region, together with the
      homeodomain, is sufficient for cardiomyogenesis in P19 cells.

PMID- 11526123
TI  - Detection of B virus antibody in monkey sera using glycoprotein D expressed in
      mammalian cells.
AB  - The gene encoding glycoprotein D (gD) of the monkey B virus (Cercopithecine
      herpesvirus 1) was cloned into a mammalian expression vector, pcDNA3.1(-), and
      the recombinant plasmid DNA was transfected into COS7 cells. The expression of gD
      in transfected COS7 cells was detected by indirect immunofluorescence assay or
      radioimmunoprecipitation analysis (RIPA). Although the expressed gD protein was
      revealed to react well with sera from monkeys naturally infected with B virus by
      RIPA, some sera showed reduced reactivity when analyzed by the Western blotting
      (WB) method. Some sera also showed relatively high background when the WB was
      performed using gD expressed from recombinant plasmid. The mutant gD protein
      lacking the transmembrane domain (TM) and cytoplasmic tail (CT) was next
      expressed in COS7 cells. The mutant protein was secreted into culture medium
      without apparent loss of the antigenicity. Using the secretory form of the gD
      protein as antigen in dot blot analysis, sera from B virus-infected monkeys were
      shown to react with the mutant protein without nonspecific reaction. Since the
      recombinant gD or its derivative lacking TM and CT could be expressed in
      mammalian cells with proper antigenicity, these antigens appeared to be useful
      for serological detection of B virus infection in monkeys.

PMID- 11526124
TI  - Citrate synthase gene sequence: a new tool for phylogenetic analysis and
      identification of Ehrlichia.
AB  - The sequence of the citrate synthase gene (gltA) of 13 ehrlichial species
      (Ehrlichia chaffeensis, Ehrlichia canis, Ehrlichia muris, an Ehrlichia species
      recently detected from Ixodes ovatus, Cowdria ruminantium, Ehrlichia
      phagocytophila, Ehrlichia equi, the human granulocytic ehrlichiosis [HGE] agent,
      Anaplasma marginale, Anaplasma centrale, Ehrlichia sennetsu, Ehrlichia risticii,
      and Neorickettsia helminthoeca) have been determined by degenerate PCR and the
      Genome Walker method. The ehrlichial gltA genes are 1,197 bp (E. sennetsu and E.
      risticii) to 1,254 bp (A. marginale and A. centrale) long, and GC contents of the
      gene vary from 30.5% (Ehrlichia sp. detected from I. ovatus) to 51.0% (A.
      centrale). The percent identities of the gltA nucleotide sequences among
      ehrlichial species were 49.7% (E. risticii versus A. centrale) to 99.8% (HGE
      agent versus E. equi). The percent identities of deduced amino acid sequences
      were 44.4% (E. sennetsu versus E. muris) to 99.5% (HGE agent versus E. equi),
      whereas the homology range of 16S rRNA genes was 83.5% (E. risticii versus the
      Ehrlichia sp. detected from I. ovatus) to 99.9% (HGE agent, E. equi, and E.
      phagocytophila). The architecture of the phylogenetic trees constructed by gltA
      nucleotide sequences or amino acid sequences was similar to that derived from the
      16S rRNA gene sequences but showed more-significant bootstrap values. Based upon
      the alignment analysis of the ehrlichial gltA sequences, two sets of primers were
      designed to amplify tick-borne Ehrlichia and Neorickettsia genogroup Ehrlichia
      (N. helminthoeca, E. sennetsu, and E. risticii), respectively. Tick-borne
      Ehrlichia species were specifically identified by restriction fragment length
      polymorphism (RFLP) patterns of AcsI and XhoI with the exception of E. muris and
      the very closely related ehrlichia derived from I. ovatus for which sequence
      analysis of the PCR product is needed. Similarly, Neorickettsia genogroup
      Ehrlichia species were specifically identified by RFLP patterns of RcaI
      digestion. If confirmed this technique will be useful in rapidly identifying
      Ehrlichia spp.

PMID- 11526125
TI  - Evidence of extrahepatic sites of replication of the hepatitis E virus in a swine
      model.
AB  - Hepatitis E virus (HEV) is the major cause of enterically transmitted non-A, non
      B hepatitis in many developing countries and is also endemic in many
      industrialized countries. Due to the lack of an effective cell culture system and
      a practical animal model, the mechanisms of HEV pathogenesis and replication are
      poorly understood. Our recent identification of swine HEV from pigs affords us an
      opportunity to systematically study HEV replication and pathogenesis in a swine
      model. In an early study, we experimentally infected specific-pathogen-free pigs
      with two strains of HEV: swine HEV and the US-2 strain of human HEV. Eighteen
      pigs (group 1) were inoculated intravenously with swine HEV, 19 pigs (group 2)
      were inoculated with the US-2 strain of human HEV, and 17 pigs (group 3) were
      used as uninoculated controls. The clinical and pathological findings have been
      previously reported. In this expanded study, we aim to identify the potential
      extrahepatic sites of HEV replication using the swine model. Two pigs from each
      group were necropsied at 3, 7, 14, 20, 27, and 55 days postinoculation (DPI).
      Thirteen different types of tissues and organs were collected from each
      necropsied animal. Reverse transcriptase PCR (RT-PCR) was used to detect the
      presence of positive-strand HEV RNA in each tissue collected during necropsy at
      different DPI. A negative-strand-specific RT-PCR was standardized and used to
      detect the replicative, negative strand of HEV RNA from tissues that tested
      positive for the positive-strand RNA. As expected, positive-strand HEV RNA was
      detected in almost every type of tissue at some time point during the viremic
      period between 3 and 27 DPI. Positive-strand HEV RNA was still detectable in some
      tissues in the absence of serum HEV RNA from both swine HEV- and human HEV
      inoculated pigs. However, replicative, negative-strand HEV RNA was detected
      primarily in the small intestines, lymph nodes, colons, and livers. Our results
      indicate that HEV replicates in tissues other than the liver. The data from this
      study may have important implications for HEV pathogenesis, xenotransplantation,
      and the development of an in vitro cell culture system for HEV.

PMID- 11526126
TI  - Rapid and accurate identification of coagulase-negative staphylococci by real
      time PCR.
AB  - Biprobe identification assays based on real-time PCR were designed for 15 species
      of coagulase-negative staphylococci (CNS). Three sets of primers and four
      biprobes were designed from two variable regions of the 16S rRNA gene. An
      identification scheme was developed based on the pattern of melting peaks
      observed with the four biprobes that had been tested on 24 type strains. This
      scheme was then tested on 100 previously identified clinical isolates and 42
      blindly tested isolates. For 125 of the 142 clinical isolates there was a perfect
      correlation between the biprobe identification and the result of the ID 32 Staph
      phenotypic tests and PCR. For 12 of the other isolates a 300-bp portion of the
      16S rRNA gene was sequenced to determine identity. The remaining five isolates
      could not be fully identified. LightCycler real-time PCR allowed rapid and
      accurate identification of the important CNS implicated in infection.

PMID- 11526127
TI  - Differentiation of metronidazole-sensitive and -resistant clinical isolates of
      Helicobacter pylori by immunoblotting with antisera to the RdxA protein.
AB  - Antimicrobial resistance in Helicobacter pylori is a serious and increasing
      problem, and the development of rapid, reliable methods for detecting resistance
      would greatly improve the selection of antibiotics used to treat gastric
      infection with this organism. We assessed whether detection of the RdxA protein
      could provide the basis for determining the susceptibility of H. pylori to
      metronidazole. In order to raise polyclonal antisera to RdxA, we cloned the rdxA
      gene from H. pylori strain 26695 into the commercial expression vector pMAL-c2,
      purified the resultant fusion protein by affinity chromatography, and used this
      recombinant RdxA preparation to immunize rabbits. We then used this specific anti
      RdxA antibody to perform immunoblotting on whole bacterial cell lysates of 17
      metronidazole-sensitive and 27 metronidazole-resistant clinical isolates of H.
      pylori. While a 24-kDa immunoreactive band corresponding to the RdxA protein was
      observed in all metronidazole-sensitive strains, this band was absent in 25 of 27
      resistant isolates. Our results indicate that testing for the absence of the RdxA
      protein would identify the majority of clinical isolates that will respond poorly
      to metronidazole-containing eradication regimens and have implications for the
      development of assays capable of detecting metronidazole resistance in H. pylori.

PMID- 11526128
TI  - LightCycler multiplex PCR for the laboratory diagnosis of common viral infections
      of the central nervous system.
AB  - A conventional multiplex PCR assay that detects herpes simplex virus type 1 (HSV
      1), HSV-2, varicella-zoster virus, and enteroviruses for the diagnosis of central
      nervous system infections was modified to be performed using the LightCycler
      system. The sensitivity of detection of each of the viruses using the LightCycler
      assay was compared to that of the conventional assay using external quality
      assessment material. The assays had equivalent sensitivities, but the LightCycler
      assay was more rapid, reduced the risk of contamination, and used an amplicon
      detection format that demonstrated greater discrimination than a gel
      electrophoresis method.

PMID- 11526129
TI  - Stx2 subtyping of Shiga toxin-producing Escherichia coli isolated from cattle in
      France: detection of a new Stx2 subtype and correlation with additional virulence
      factors.
AB  - At least 11 Stx2 variants produced by Shiga toxin-producing Escherichia coli
      (STEC) isolated from patients and animals have been described. The Stx2 subtyping
      of STEC isolated from healthy cows positive for stx(2) (n = 104) or stx(2) and
      stx(1) (n = 63) was investigated. Stx2vh-b, Stx2 (renamed Stx2-EDL933), and
      Stx2vh-a were the subtypes mostly detected among the bovine isolates (39.5, 39,
      and 25.5%, respectively). Stx2e was not present, and subtypes included in the
      Stx2d group (Stx2d-OX3a, Stx2d-O111, and Stx2d-Ount) were found infrequently
      among the isolates examined (8.5%). A combination of two distinct Stx2 subtypes
      was observed among 23.5% of the strains. For the first time, a combination of
      three subtypes (Stx2-EDL933/Stx2vh-b/Stx2d and Stx2vh-a/Stx2vh-b/Stx2d) was
      detected (3.5% of the isolates). In addition, bovine STEC harboring stx(1) and
      one or two stx(2) genes appeared highly cytotoxic toward Vero cells. A new Stx2
      subtype (Stx2-NV206), present among 14.5% of the isolates, showed high
      cytotoxicity for Vero cells. Two amino acid residues (Ser-291 and Glu-297)
      important for the activation of Stx2 by human intestinal mucus were conserved on
      the Stx2-NV206 A subunit. The gene encoding Ehx enterohemolysin was prominent
      among STEC harboring stx(2)-EDL933 alone (78%) or a combination of stx(2)-EDL933
      and stx(2)vh-b (85%). In addition, Stx2-EDL933 and/or Stx2vh-b subtypes were
      highly associated with other putative virulence factors such as Stx1 and EspP
      extracellular serine protease, but not with EAST1 enterotoxin.

PMID- 11526130
TI  - Semiautomation of multilocus sequence typing for the characterization of clinical
      isolates of Neisseria meningitidis.
AB  - The Scottish Meningococcus and Pneumococcus Reference Laboratory (SMPRL) provides
      a national service for the laboratory confirmation of meningococcal and
      pneumococcal disease in Scotland. Part of this service includes the serogrouping
      of meningococcal isolates followed by typing and subtyping. The procedures for
      this are labor-intensive but important for the identification of linked cases and
      the surveillance of disease so that effective public health measures can be
      taken. However, different strains of meningococci, such as those within the
      electrophoretic type 37 complex, occurring during case clusters of disease are
      now indistinguishable by current methods. The SMPRL has started using multilocus
      sequence typing (MLST) as a routine method for the characterization of isolates
      of Neisseria meningitidis. MLST produces nucleotide sequence data of seven
      housekeeping genes providing results that are useful for public health
      management. However, the method is laborious and time-consuming and therefore
      lends itself towards automation. The SMPRL therefore developed a semiautomated
      method for MLST using a 96-well format liquid handler and an automated DNA
      sequencer. Semiautomated MLST is now provided as a reference service for
      Scotland. This work describes the methodology required for the characterization
      of N. meningitidis and highlights its usefulness for public health intervention.

PMID- 11526131
TI  - PCR detection and molecular identification of Chlamydiaceae species.
AB  - Recent taxonomic developments, based on 16s and 23s rRNA gene sequences, have
      divided the family Chlamydiaceae into two genera and nine species, of which five
      have been found to infect humans. Few simple methods are available to detect and
      identify all species sensitively and specifically. In this study the suitability
      of the omp2 gene as a target for molecular identification of Chlamydiaceae is
      demonstrated. Phylogenetic analysis of partial omp2 gene sequences from all nine
      species agrees with the recently published taxonomic changes based on the
      ribosomal genes. The use of a family-specific PCR primer pair, which is able to
      amplify the 5' end of the omp2 gene from all Chlamydiaceae except some
      Chlamydophila pecorum strains, is described. Identification of all nine species
      was achieved using restriction fragment length polymorphism analysis with a
      single enzyme, AluI, confirmed by DNA sequencing. A PCR enzyme-linked
      oligonucleotide assay was developed which can detect a single chlamydial genome
      and may be applied to DNA extracts from any specimen or culture for the detection
      of single or mixed human chlamydial infection.

PMID- 11526132
TI  - Experimental paratuberculosis in calves following inoculation with a rabbit
      isolate of Mycobacterium avium subsp. paratuberculosis.
AB  - The role of wildlife species in the epidemiology of paratuberculosis has been the
      subject of increased research efforts following the discovery of natural
      paratuberculosis in free-living rabbits from farms in east Scotland. This paper
      describes the experimental inoculation of young calves with an isolate of
      Mycobacterium avium subsp. paratuberculosis recovered from a free-living rabbit.
      After a 6-month incubation period, all eight calves inoculated with the rabbit
      isolate had developed histopathological and/or microbiological evidence of M.
      avium subsp. paratuberculosis infection. Similar results were obtained from a
      group of calves infected with a bovine isolate of M. avium subsp.
      paratuberculosis. The virulence of the rabbit isolate for calves demonstrated in
      this study suggests that rabbits are capable of passing paratuberculosis to
      domestic ruminants and that wildlife reservoirs of M. avium subsp.
      paratuberculosis should therefore be considered when formulating control plans
      for the disease.

PMID- 11526133
TI  - Identification of Mycobacterium species by multiple-fluorescence PCR-single
      strand conformation polymorphism analysis of the 16S rRNA gene.
AB  - Identification of mycobacteria to the species level by growth-based methodologies
      is a process that has been fraught with difficulties due to the long generation
      times of mycobacteria. There is an increasing incidence of unusual nontuberculous
      mycobacterial infections, especially in patients with concomitant
      immunocompromised states, which has led to the discovery of new mycobacterial
      species and the recognition of the pathogenicity of organisms that were once
      considered nonpathogens. Therefore, there is a need for rapid and sensitive
      techniques that can accurately identify all mycobacterial species. Multiple
      fluorescence-based PCR and subsequent single-strand conformation polymorphism
      (SSCP) analysis (MF-PCR-SSCP) of four variable regions of the 16S rRNA gene were
      used to identify species-specific patterns for 30 of the most common
      mycobacterial human pathogens and environmental isolates. The species-specific
      SSCP patterns generated were then entered into a database by using BioNumerics,
      version 1.5, software with a pattern-recognition capability, among its multiple
      uses. Patient specimens previously identified by 16S rRNA gene sequencing were
      subsequently tested by this method and were identified by comparing their
      patterns with those in the reference database. Fourteen species whose SSCP
      patterns were included in the database were correctly identified. Five other test
      organisms were correctly identified as unique species or were identified by their
      closest relative, as they were not in the database. We propose that MF-PCR-SSCP
      offers a rapid, specific, and relatively inexpensive identification tool for the
      differentiation of mycobacterial species.

PMID- 11526134
TI  - Enhancing the specificity of the COBAS AMPLICOR CT/NG test for Neisseria
      gonorrhoeae by retesting specimens with equivocal results.
AB  - The COBAS AMPLICOR CT/NG test for Neisseria gonorrhoeae cross-reacts with certain
      strains of nonpathogenic Neisseria species. In some strains, the target sequence
      is identical to that of N. gonorrhoeae, whereas other strains have a small number
      of mismatches within the regions recognized by the primers or probe used in the
      COBAS AMPLICOR NG test. These cross-reactive strains are occasionally present in
      urogenital specimens, causing false-positive results in the COBAS AMPLICOR NG
      test. Analysis of the data generated in a large multicenter clinical trial showed
      that 2.9% of the specimens gave signals between A(660)s of 0.2 and 3.5 but that
      one-half of these equivocal specimens did not contain N. gonorrhoeae. Most of
      these equivocal specimens were correctly classified as true positive or true
      negative by retesting in duplicate and defining a PCR-positive result as two of
      three results with an A(660) of > or =2.0. If specimens had been classified as
      positive or negative based on a single test result using a cutoff of an A(660) of
      0.2, specificity would have ranged from 96.2 to 98.9% depending on specimen type,
      sex, and presence of symptoms. By employing the equivocal zone-retesting
      algorithm, specificity increased to 98.6 to 99.9% with little effect (0.1 to 4.9%
      decrease) on sensitivity in most specimen types, enabling the test to achieve a
      positive predictive value of at least 90% in populations with a prevalence of 4%
      or higher. In lower-prevalence populations, the test could be used to screen for
      presumptive infections that would have to be confirmed by an independent test.

PMID- 11526135
TI  - Identification of clinical staphylococcal isolates from humans by internal
      transcribed spacer PCR.
AB  - The emergence of coagulase-negative staphylococci not only as human pathogens but
      also as reservoirs of antibiotic resistance determinants requires the deployment
      and development of methods for their rapid and reliable identification. Internal
      transcribed spacer-PCR (ITS-PCR) was used to identify a collection of 617
      clinical staphylococcal isolates. The amplicons were resolved in high-resolution
      agarose gels and visually compared with the patterns obtained for the control
      strains of 29 staphylococcal species. Of the 617 isolates studied, 592 (95.95%)
      were identified by ITS-PCR and included 11 species: 302 isolates of
      Staphylococcus epidermidis, 157 of S. haemolyticus, 79 of S. aureus, 21 of S.
      hominis, 14 of S. saprophyticus, 8 of S. warneri, 6 of S. simulans, 2 of S.
      lugdunensis, and 1 each of S. caprae, S. carnosus, and S. cohnii. All species
      analyzed had unique ITS-PCR patterns, although some were very similar, namely,
      the group S. saprophyticus, S. cohnii, S. gallinarum, S. xylosus, S. lentus, S.
      equorum, and S. chromogenes, the pair S. schleiferi and S. vitulus, and the pair
      S. piscifermentans and S. carnosus. Four species, S. aureus, S. caprae, S.
      haemolyticus, and S. lugdunensis, showed polymorphisms on their ITS-PCR patterns.
      ITS-PCR proved to be a valuable alternative for the identification of
      staphylococci, offering, within the same response time and at lower cost, higher
      reliability than the currently available commercial systems.

PMID- 11526136
TI  - Identification of strains of Alcaligenes and Agrobacterium by a polyphasic
      approach.
AB  - The number of stable discriminant biochemical characters is limited in the genera
      Alcaligenes and Agrobacterium, whose species are consequently difficult to
      distinguish from one another by conventional tests. Moreover, genomic studies
      have recently drastically modified the nomenclature of these genera; for example,
      Alcaligenes xylosoxidans was transferred to the genus Achromobacter in 1998.
      Twenty-five strains of Achromobacter xylosoxidans, three strains of an
      Agrobacterium sp., five strains of an Alcaligenes sp., and four unnamed strains
      belonging to the Centers for Disease Control and Prevention group IVc-2 were
      examined. These strains were characterized by conventional tests, including
      biochemical tests. The assimilation of 99 carbohydrates, organic acids, and amino
      acids was studied by using Biotype-100 strips, and rRNA gene restriction patterns
      were obtained with the automated Riboprinter microbial characterization system
      after cleavage of total DNA with EcoRI or PstI restriction endonuclease. This
      polyphasic approach allowed the two subspecies of A. xylosoxidans to be clearly
      separated. Relationships between five strains and the Ralstonia paucula type
      strain were demonstrated. Likewise, three strains were found to be related to the
      Ochrobactrum anthropi type strain. We showed that substrate assimilation tests
      and automated ribotyping provide a simple, rapid, and reliable means of
      identifying A. xylosoxidans subspecies and that these two methods can be used as
      alternative methods to characterize unidentified strains rapidly when
      discriminant biochemical characters are missing.

PMID- 11526137
TI  - Novel approach to reduce the hepatitis C virus (HCV) window period: clinical
      evaluation of a new enzyme-linked immunosorbent assay for HCV core antigen.
AB  - The window period in hepatitis C virus (HCV) infection is still a major problem
      in ensuring blood safety. HCV RNA detection by nucleic acid amplification
      technology-based tests has contributed to reduce the infectivity of blood
      products, but it is expensive, time-consuming and affected by a high prevalence
      of false-positive results. The aim of this study was to assess the performance of
      a newly developed enzyme immunoassay for the detection of HCV core antigen and
      its suitability for use in the screening of blood units in order to identify
      infecting samples that do not contain specific antibodies. For evaluation of
      laboratory performance, different samples were selected: to evaluate specificity,
      we tested 2,586 sera from blood donors, 500 general population samples, and 58
      "difficult sera". All samples were tested by two screening assays, and results
      were negative. To estimate clinical sensitivity, 103 HCV RNA-positive, anti-HCV
      negative samples, 6 natural seroconversion panels, and 9 commercial
      seroconversion panels were tested. Intra- and interassay precision were
      determined on two HCV-RNA-positive, anti-HCV-negative sera. Seventeen (0.66%)
      blood donor samples, 2 (0.4%) general population samples, and 2 (3.44%) difficult
      sera were initially reactive; 3 sera were positive on repetition. These 21
      samples tested by reverse transcription-PCR were negative. The clinical
      sensitivity calculated with seroconversion panels and seroconverted patient
      samples was very similar to PCR sensitivity: 95% of PCR-positive, antibody
      negative samples contained detectable HCV antigen. Data on intra- and interassay
      precision showed dispersion indices with values of less than 10%. In conclusion,
      the HCV antigen assay showed high sensitivity and specificity and could become a
      useful means of improving the safety of blood and blood products.

PMID- 11526138
TI  - Identification of aminoglycoside-modifying enzymes by susceptibility testing:
      epidemiology of methicillin-resistant Staphylococcus aureus in Japan.
AB  - A multiple-primer PCR was used to identify genes encoding aminoglycoside
      modifying enzymes in 381 clinical isolates of methicillin-resistant
      Staphylococcus aureus (MRSA). The technique used three sets of primers
      delineating specific DNA fragments of the aph(3')-III, ant(4')-I, and aac(6')
      aph(2") genes, which influence the MICs of gentamicin, tobramycin, and
      lividomycin. Isolates with none of the three genes detected were susceptible to
      all three agents. Isolates with the aph(3')-III gene showed resistance to
      lividomycin (MIC > 1,024 microg/ml), and those with the ant(4')-I gene were
      resistant to tobramycin (MIC > or = 8 microg/ml). Isolates with only the aac(6')
      aph(2") gene were resistant to gentamicin (MIC > or = 8 microg/ml) and tobramycin
      in decreasing order; those with both the ant(4')-I and aac(6')-aph(2") genes also
      were resistant to gentamicin and tobramycin, but in increasing order.
      Susceptibility testing, then, could detect specific genes. In 381 Japanese MRSA
      isolates, the ant(4')-I, aac(6')-aph(2"), and aph(3')-III genes were prevalent in
      84.5, 61.7, and 8.9%, respectively. Isolates with only the ant(4')-I gene had
      coagulase type II or III, but isolates with both the ant(4')-I and aac(6')
      aph(2") genes included all coagulase types. Most isolates with coagulase type IV
      or VII carried the aac(6')-aph(2") gene. Of the MRSA isolates with ant(4')-I
      and/or aac(6')-aph(2") genes, 97% were resistant to aminoglycosides in clinical
      use, but a new aminoglycoside, arbekacin, had excellent activity against these
      isolates.

PMID- 11526139
TI  - Seven human immunodeficiency virus (HIV) antigen-antibody combination assays:
      evaluation of HIV seroconversion sensitivity and subtype detection.
AB  - In this study, we evaluated the performance of two prototype human
      immunodeficiency virus (HIV) antigen-antibody (Ag-Ab) combination assays, one
      from Abbott Laboratories (AxSYM HIV Ag-Ab) and the other from bioMerieux (VIDAS
      HIV Duo Ultra), versus five combination assays commercially available in Europe.
      The assays were Enzygnost HIV Integral, Genscreen Plus HIV Ag-Ab, Murex HIV Ag-Ab
      Combination, VIDAS HIV Duo, and Vironostika HIV Uniform II Ag-Ab. All assays were
      evaluated for the ability to detect p24 antigen from HIV-1 groups M and O,
      antibody-positive plasma samples from HIV-1 groups M and O, HIV-2, and 19 HIV
      seroconversion panels. Results indicate that although all combination assays can
      detect antibodies to HIV-1, group M, subtypes A to G, circulating recombinant
      form (CRF) A/E, and HIV-1 group O, their sensitivity varied considerably when
      tested using diluted HIV-1 group O and HIV-2 antibody-positive samples. Among
      combination assays, the AxSYM, Murex, and VIDAS HIV Duo Ultra assays exhibited
      the best antigen sensitivity (at approximately 25 pg of HIV Ag/ml) for detection
      of HIV-1 group M, subtypes A to G and CRF A/E, and HIV-1 group O isolates.
      However, the VIDAS HIV Duo Ultra assay had a lower sensitivity for HIV-1 group M
      and subtype C, and was unable to detect subtype C antigen even at 125 pg of HIV
      Ag/ml. The HIV antigen sensitivity of the VIDAS HIV Duo and Genscreen Plus
      combination assays was approximately 125 pg of HIV Ag/ml for detection of all HIV
      1 group M isolates except HIV-1 group O while the sensitivity of Vironostika HIV
      Uniform II Ag-Ab and Enzygnost HIV Integral Ag-Ab assays for all the group M
      subtypes was >125 pg of HIV Ag/ml. Among the combination assays, the AxSYM assay
      had the best performance for detection of early seroconversion samples, followed
      by the Murex and VIDAS HIV Duo Ultra assays.

PMID- 11526140
TI  - Quantitative detection of Streptococcus pneumoniae in nasopharyngeal secretions
      by real-time PCR.
AB  - Streptococcus pneumoniae is an important cause of community-acquired pneumonia.
      However, in this setting the diagnostic sensitivity of blood cultures is below
      30%. Since during such infections changes in the amounts of S. pneumoniae may
      also occur in the upper respiratory tract, quantification of these bacteria in
      nasopharnygeal secretions (NPSs) may offer a suitable diagnostic approach. Real
      time PCR offers a sensitive, efficient, and routinely reproducible approach to
      quantification. Using primers and a fluorescent probe specific for the
      pneumolysin gene, we were able to detect DNA from serial dilutions of S.
      pneumoniae cells in which the quantities of DNA ranged from the amounts extracted
      from 1 to 10(6) cells. No difference was noted when the same DNA was mixed with
      DNA extracted from NPSs shown to be deficient of S. pneumoniae following culture,
      suggesting that this bacterium can be detected and accurately quantitated in
      clinical samples. DNAs from Haemophilus influenzae, Moraxella catarrhalis, or
      alpha-hemolytic streptococci other than S. pneumoniae were not amplified or were
      only weakly amplified when there were > or =10(6) cells per reaction mixture.
      When the assay was applied to NPSs from patients with respiratory tract
      infections, the assay performed with a sensitivity of 100% and a specificity of
      up to 96% compared to the culture results. The numbers of S. pneumoniae organisms
      detected by real-time PCR correlated with the numbers detected by
      semiquantitative cultures. A real-time PCR that targeted the pneumolysin gene
      provided a sensitive and reliable means for routine rapid detection and
      quantification of S. pneumoniae present in NPSs. This assay may serve as a tool
      to study changes in the amounts of S. pneumoniae during lower respiratory tract
      infections.

PMID- 11526141
TI  - Reliable detection of respiratory syncytial virus infection in children for
      adequate hospital infection control management.
AB  - By using a rapid test for respiratory syncytial virus (RSV) detection (Abbott
      TestPack RSV), a number of patients were observed, showing repeatedly positive
      results over a period of up to 10 weeks. A prospective study was initiated to
      compare the rapid test with an antigen capture enzyme immunoassay (EIA) and a
      nested reverse transcriptase PCR (RT-PCR) protocol for detection of RSV serotypes
      A and B. Only respiratory samples from children exhibiting the prolonged presence
      of RSV (> or =5 days) as determined by the rapid test were considered. A total of
      134 specimens from 24 children was investigated by antigen capture EIA and nested
      RT-PCR. Using RT-PCR as the reference method, we determined the RSV rapid test to
      have a specificity of 63% and a sensitivity of 66% and the antigen capture EIA to
      have a specificity of 96% and a sensitivity of 69% for acute-phase samples and
      the homologous virus serotype A. In 7 (29%) of 24 patients, the positive results
      of the RSV rapid test could not be confirmed by either nested RT-PCR or antigen
      capture EIA. In these seven patients a variety of other respiratory viruses were
      detected. For general screening the RSV rapid test was found to be a reasonable
      tool to get quick results. However, its lack of specificity in some patients
      requires confirmation by additional tests to rule out false-positive results
      and/or detection of other respiratory viruses.

PMID- 11526142
TI  - Extensive allelic variation among Francisella tularensis strains in a short
      sequence tandem repeat region.
AB  - Members of the genus Francisella and the species F. tularensis appear to be
      genetically very similar despite pronounced differences in virulence and
      geographic localization, and currently used typing methods do not allow
      discrimination of individual strains. Here we show that a number of short
      sequence tandem repeat (SSTR) loci are present in F. tularensis genomes and that
      two of these loci, SSTR9 and SSTR16, are together highly discriminatory. Labeled
      PCR amplification products from the loci were identified by an automated DNA
      sequencer for size determination, and each allelic variant was sequenced.
      Simpson's index of diversity was 0.97 based on an analysis of 39 nonrelated F.
      tularensis isolates. The locus showing the highest discrimination, SSTR9, gave an
      index of diversity of 0.95. Thirty-two strains isolated from humans during five
      outbreaks of tularemia showed much less variation. For example, 11 of 12 strains
      isolated in the Ljusdal area, Sweden in 1995 and 1998 had identical allelic
      variants. Phenotypic variants of strains and extensively cultured replicates
      within strains did not differ, and, for example, the same allelic combination was
      present in 55 isolates of the live-vaccine strain of F. tularensis and another
      one was present in all 13 isolates of a strain passaged in animals. The analysis
      of short-sequence repeats of F. tularensis strains appears to be a powerful tool
      for discrimination of individual strains and may be useful for a detailed
      analysis of the epidemiology of this potent pathogen.

PMID- 11526143
TI  - Group G beta-hemolytic streptococcal bacteremia characterized by 16S ribosomal
      RNA gene sequencing.
AB  - Little is known about the relative importance of the four species of Lancefield
      group G beta-hemolytic streptococci in causing bacteremia and the factors that
      determine the outcome for patients with group G beta-hemolytic streptococcal
      bacteremia. From 1997 to 2000, 75 group G beta-hemolytic streptococcal strains
      were isolated from the blood cultures of 66 patients. Sequencing of the 16S rRNA
      genes of the group G beta-hemolytic streptococci showed that all 75 isolates were
      Streptococcus dysgalactiae subspecies equisimilis. The API system (20 STREP) and
      Vitek system (GPI) successfully identified 65 (98.5%) and 62 (93.9%) isolates,
      respectively, as S. dysgalactiae subspecies equisimilis with >95% confidence,
      whereas the ATB Expression system (ID32 STREP) only successfully identified 49
      isolates (74.2%) as S. dysgalactiae subspecies equisimilis with >95% confidence.
      The median age of the patients was 76 years (range, 33 to 99 years). Fifty-six
      patients (85%) were over 60 years old. All patients had underlying diseases. No
      source of the bacteremia was identified (primary bacteremia) in 34 patients
      (52%), whereas 17 (26%) had cellulitis and 8 (12%) had bed sore or wound
      infections. Fifty-eight patients (88%) had community-acquired group G
      streptococcal bacteremia. Sixty-two patients (94%) had group G Streptococcus
      recovered in one blood culture, whereas 4 patients (6%) had it recovered in
      multiple blood cultures. Fifty-nine patients (89%) had group G Streptococcus as
      the only bacterium recovered in their blood cultures, whereas in 7 patients other
      bacteria were recovered concomitantly with the group G Streptococcus in the blood
      cultures (Staphylococcus aureus in 3, Clostridium perfringens in 2, Citrobacter
      freundii in 1, and Bacteroides fragilis in 1). Overall, 10 patients (15%) died.
      Male sex, diagnosis other than cellulitis, hospital-acquired bacteremia, and
      multiple positive blood cultures were associated with mortality [P < 0.005
      (relative risk [RR] = 7.6), P < 0.05 (RR = 3.7), P < 0.005 (RR = 5.6), and P <
      0.05 (RR = 5.6), respectively]. Unlike group C beta-hemolytic streptococcal
      bacteremia, group G beta-hemolytic streptococcal bacteremia is not a zoonotic
      infection in Hong Kong.

PMID- 11526144
TI  - Enzyme-linked immunosorbent assay for detecting herpesvirus exposure in
      Mediterranean tortoises (spur-thighed tortoise [Testudo graeca] and Hermann's
      tortoise [Testudo hermanni]).
AB  - An enzyme-linked immunosorbent assay (ELISA) was developed for the detection of
      antibodies to a herpesvirus associated with an upper respiratory tract disease in
      Mediterranean tortoises [spur-thighed tortoise (Testudo graeca) and Hermann's
      tortoise (Testudo hermanni)]. This serodiagnostic test was validated through a
      hyperimmunization study. The mean of the A(405) readings of the plasma samples
      collected at time zero of the hyperimmunization study plus three times the
      standard deviation was used as the cutoff for seropositivity in tortoises. ELISA
      results were compared to serum neutralization (SN) values for the same samples by
      using the McNemar test. The results obtained by SN and ELISA were not
      significantly different (P > 0.05). This new ELISA could be used as an important
      diagnostic tool for screening wild populations and private and zoo collections of
      Mediterranean tortoises.

PMID- 11526145
TI  - Antibody responses to recombinant Epstein-Barr virus antigens in nasopharyngeal
      carcinoma patients: complementary test of ZEBRA protein and early antigens p54
      and p138.
AB  - Serological tests based on the antibodies directed against the Epstein-Barr virus
      early antigen (EA) and viral capsid antigen (VCA), which have been recognized as
      tumor markers for nasopharyngeal carcinoma (NPC), are routinely used to help in
      the diagnosis of this malignancy. The detection of these antibodies reveals very
      low titers, found only in a small proportion of young compared with older NPC
      patients. This is a problem for the diagnosis of NPC, especially among
      Maghrebians, among whom young people are also affected, and emphasizes the
      necessity to search for more reliable markers. The present study reports results
      of immunoglobulin G (IgG) and IgA responses of NPC patients to recombinant EA
      antigens p54 (BMRF1) and p138 (BALF2), VCA complex antigens p18 (BFRF3) and p23
      (BLRF2), and EBNA antigen p72 (BKRF1). Our results show that IgA-EA-p54 and -p138
      (IgA-EA-p54+138) antibodies have a diagnostic value for detection of NPC (70%),
      compared with IgA-VCA-p18+23 and IgA-EBNA-p72, which have limited diagnostic
      value, especially in young patients. It is also noteworthy that IgA-EA-p54+138
      can detect a high percentage (64%) of NPC cases negative by immunofluorescence.
      These results, however, clearly show that a single test cannot achieve the
      objective of detecting all NPC patients, and it seems advisable to combine
      different tests for the diagnosis of NPC. The combination of IgG-ZEBRA with IgA
      EA-p54+138 improved the sensitivity of detection of NPC to 95% in the overall NPC
      population. The use of IgA-EA-p54+138 in combination with IgG-ZEBRA will
      facilitate detailed studies on the pattern of antibody response, which may result
      in the development of useful serological markers to guide the treatment of NPC.

PMID- 11526146
TI  - Use of a heteroduplex mobility assay to detect differences in the fusion protein
      cleavage site coding sequence among Newcastle disease virus isolates.
AB  - Newcastle disease virus (NDV) is an economically important pathogen of poultry
      that may cause clinical disease that ranges from a mild respiratory syndrome to a
      virulent form with high mortality, depending on an isolate's pathotype.
      Infections with virulent NDV strains are required to be reported by member
      nations to the Office of International Epizootes (OIE). The primary determinant
      for virulence among NDV isolates is the presence or absence of dibasic amino
      acids in the fusion (F) protein cleavage activation site. Along with biological
      virulence determinations as the definitive tests, OIE accepts reporting of the F
      protein cleavage site sequence of NDV isolates as a virulence criterion.
      Nucleotide sequence data for many NDV isolates recently isolated from infected
      chickens and other avian species worldwide have been deposited in GenBank.
      Consequently, viral genomic information surrounding the F protein cleavage site
      coding sequence was used to develop a heteroduplex mobility assay (HMA) to aid in
      further identification of molecular markers as predictors of NDV virulence. Using
      common vaccine strains as a reference, we were able to distinguish virulent
      viruses among NDV isolates that correlated with phylogenetic analysis of the
      nucleotide sequence. This technique was also used to examine NDV isolates not
      previously characterized. We were able to distinguish vaccine-like viruses from
      other isolates potentially virulent for chickens. This technique will help
      improve international harmonization of veterinary biologics as set forth by the
      OIE and the Veterinary International Cooperation on Harmonization of Technical
      Requirements of Veterinary Medicinal Products. Ultimately, the HMA could be used
      for initial screening among a large number of isolates and rapid identification
      of potentially virulent NDV that continue to threaten commercial poultry
      worldwide.

PMID- 11526147
TI  - Identification and characterization of variable-number tandem repeats in the
      Yersinia pestis genome.
AB  - Yersinia pestis, the infamous plague-causing pathogen, appears to have emerged in
      relatively recent history. Evidence of this fact comes from several studies that
      document a lack of nucleotide diversity in the Y. pestis genome. In contrast, we
      report that variable-number tandem repeat (VNTR) sequences are common in the Y.
      pestis genome and occur frequently in gene coding regions. Larger tandem repeat
      arrays, most useful for phylogenetic analysis, are present at an average of 2.18
      arrays per 10 kbp and are distributed evenly throughout the genome and the two
      virulence plasmids, pCD1 and pMT1. We examined allelic diversity at 42
      chromosomal VNTR loci in 24 selected isolates (12 globally distributed and 12
      from Siskiyou County, Calif.). Vast differences in diversity were observed among
      the 42 VNTR loci, ranging from 2 to 11 alleles. We found that the maximum copy
      number of repeats in an array was highly correlated with diversity (R = 0.86).
      VNTR-based phylogenetic analysis of the 24 strains successfully grouped isolates
      from biovar orientalis and most of the antiqua and mediaevalis strains. Hence,
      multiple-locus VNTR analysis (MLVA) appears capable of both distinguishing
      closely related strains and successfully classifying more distant relationships.
      Harnessing the power of MLVA to establish standardized databases will enable
      researchers to better understand plague ecology and evolution around the world.

PMID- 11526148
TI  - Francisella tularensis strain typing using multiple-locus, variable-number tandem
      repeat analysis.
AB  - Francisella tularensis, the etiological agent of tularemia, is found throughout
      the Northern hemisphere. After analyzing the F. tularensis genomic sequence for
      potential variable-number tandem repeats (VNTRs), we developed a multilocus VNTR
      analysis (MLVA) typing system for this pathogen. Variation was detected at six
      VNTR loci in a set of 56 isolates from California, Oklahoma, Arizona, and Oregon
      and the F. tularensis live vaccine strain. PCR assays revealed diversity at these
      loci with total allele numbers ranging from 2 to 20, and Nei's diversity index
      values ranging from 0.36 to 0.93. Cluster analysis identified two genetically
      distinct groups consistent with the current biovar classification system of F.
      tularensis. These findings suggest that these VNTR markers are useful for
      identifying F. tularensis isolates at this taxonomic level. In this study, biovar
      B isolates were less diverse than those in biovar A, possibly reflecting the
      history of tularemia in North America. Seven isolates from a recent epizootic in
      Maricopa County, Ariz., were identical at all VNTR marker loci. Their identity,
      even at a hypervariable VNTR locus, indicates a common source of infection. This
      demonstrates the applicability of MLVA for rapid characterization and
      identification of outbreak isolates. Future construction of reference databases
      will allow faster outbreak tracking as well as providing a foundation for
      deciphering global genetic relationships.

PMID- 11526149
TI  - Outbreak of infection with extended-spectrum beta-lactamase-producing Klebsiella
      pneumoniae in a Mexican hospital.
AB  - Thirty-one strains of Klebsiella pneumoniae (including 10 duplicates) from 21
      septicemic pediatric patients (age, <2 months) were studied during a 4-month
      period (June to October 1996) in which the fatality rate was 62% (13 of 21).
      These isolates identified by the API 20E system yielded the same biotype. Pulsed
      field gel electrophoresis experiments revealed the same clone in 31 strains. The
      isolates were multidrug-resistant but were still susceptible to ciprofloxacin,
      imipenem, and cefoxitin. A 135-kb plasmid was harbored in all of the isolates. No
      transconjugants were obtained that were resistant to ampicillin, cefotaxime,
      tetracycline, or gentamicin. Isoelectric focusing for beta-lactamases was
      performed on all strains, and three bands with pIs of 5.4, 7.6, and 8.2 were
      obtained. Of these, the pI 8.2 beta-lactamase had an extended-spectrum beta
      lactamase phenotype. PCR amplification of both TEM- and SHV-type genes was
      obtained. The sequence analysis of the SHV PCR product indicated a mutation
      corresponding to the SHV-5 beta-lactamase.

PMID- 11526150
TI  - Evaluation of the Affirm Ambient Temperature Transport System for the detection
      and identification of Trichomonas vaginalis, Gardnerella vaginalis, and Candida
      species from vaginal fluid specimens.
AB  - The objective of this study was to measure the performance of the Affirm Ambient
      Temperature Transport System (ATTS) over time and to estimate the length of time
      the system can preserve a vaginal specimen containing the three common organisms
      causing vaginitis: Trichomonas vaginalis, Candida species, and Gardnerella
      vaginalis (one of the causative agents of bacterial vaginosis). Women with
      symptoms of vaginitis presenting to one of three clinical centers were evaluated
      over a 4- to 8-week period. Four simultaneously obtained swabs were collected and
      tested by the Affirm VPIII assay at time zero with and without a preservative
      reagent, at 24 h with reagent, and at either 48 or 72 h with reagent. For each of
      the three organisms, Trichomonas, Gardnerella, and Candida, positivity at each
      time point was evaluated and compared to that at reference time zero with and
      without the ATTS. A total of 940 specimens were obtained from the three clinical
      sites. Eight hundred three were positive for one or more of the three organisms.
      Gardnerella had the highest overall positive rate (62%), followed by Candida with
      18% and Trichomonas at 9%. The percent sensitivity versus control for Trichomonas
      ranged from 100% at time zero with and without reagent to 91% by 72 h.
      Gardnerella and Candida sensitivity remained at 100% for each time period. The
      Affirm VPIII ATTS system performed within 10% of the control swab (no transport
      reagent) at all four time points (0, 24, 48, and 72 h) for Trichomonas,
      Gardnerella, and Candida.

PMID- 11526151
TI  - Phylogenetic origin of hepatitis B virus strains with precore C-1858 variant.
AB  - Mutations that prevent the expression of the hepatitis B e antigen frequently
      emerge in the immunoreactive phase of infection. The predominant mutation, the
      precore G-->A-1896 mutation, is restricted by the variability at position 1858
      and is rare in strains with cytosine at nucleotide 1858. The C-1858 variant is
      characteristic of genotype A. It also occurs in genotypes C and F, but not in B,
      D, or E, explaining the geographical variation in the prevalence of precore
      mutants. C-1858 strains have been frequently observed in southeast Asia, but have
      not been phylogenetically characterized. By sequencing eight complete hepatitis B
      virus genomes, C-1858 variants of east Asian origin were found to constitute a
      phylogenetic entity within genotype C that probably diverged several hundred
      years ago. Further study of the distribution of this variant is warranted.

PMID- 11526152
TI  - Novel method for detection, typing, and quantification of human papillomaviruses
      in clinical samples.
AB  - We report the development of a novel detection and typing methodology for human
      papillomaviruses (HPV) based on real-time PCR with the self-probing fluorescent
      primers known as Scorpions. This technique is quick, simple, specific, sensitive,
      and capable of estimating viral load per cell. We report the results of over 100
      typing reactions performed on cell lines, biopsies, and cervical cytobrush
      samples which, when compared to the current reference HPV detection and typing
      technique, present a kappa value of 0.89. We further report preliminary data
      suggesting a relationship between viral load per cell and grade of cervical
      disease.

PMID- 11526154
TI  - Direct identification of mycobacteria from MB/BacT alert 3D bottles: comparative
      evaluation of two commercial probe assays.
AB  - The new INNO-LiPA Mycobacteria (Innogenetics, Ghent, Belgium), a reverse
      hybridization-based line probe assay, and the AccuProbe assay (Gen-Probe Inc.,
      San Diego, Calif.) were applied to MB/BacT Alert 3D (MB/BacT) system (Organon
      Teknika, Boxtel, The Netherlands) culture bottles and evaluated for mycobacterial
      identification. From 2,532 respiratory and extrapulmonary specimens submitted for
      culture, 168 were flagged positive by the MB/BacT system and promptly evaluated
      for identification (within 24 h). Each of 163 vials grew one mycobacterial
      isolate, including Mycobacterium tuberculosis complex (n = 73), M. avium complex
      (n = 3), M. avium (n = 8), M. intracellulare (n = 5), M. kansasii (n = 15), M.
      gordonae (n = 8), M. malmoense (n = 3), M. chelonae (n = 13), M. abscessus (n =
      2), M. xenopi (n = 11), M. scrofulaceum (n = 2), M. fortuitum (n = 7), M. terrae
      (n = 3), M. simiae (n = 2), M. celatum (n = 3), M. flavescens (n = 1), M.
      interjectum (n = 1), M. bohemicum (n = 1), and M. pulveris (n = 2). Five cultures
      yielded mixed growth of two mycobacterial species: M. tuberculosis complex plus
      M. gordonae (n = 2), M. tuberculosis complex plus M. chelonae (n = 1), M.
      tuberculosis complex plus M. xenopi (n = 1), and M. avium plus M. chelonae (n =
      1). In testing of one-isolate vials, both systems showed excellent sensitivity
      and specificity for all species and complexes for which they are licensed (nine
      for INNO-LiPA Mycobacteria versus six for AccuProbe). There were minor
      discrepancies in results for two isolates identified by INNO-LiPA Mycobacteria as
      M. avium - M. intracellulare - M. scrofulaceum (MAIS) complex and by AccuProbe as
      M. intracellulare. In testing of two-isolate vials, INNO-LiPA Mycobacteria
      correctly identified all isolates, while the AccuProbe assay failed to identify
      three M. tuberculosis complex isolates and one M. avium isolate. The AccuProbe
      assay was completed within 2 h, while INNO-LiPA Mycobacteria required a 6-h
      period. In our opinion, INNO-LiPA Mycobacteria offers the following advantages:
      (i) it contains a genus-specific probe that, in addition to being used in genus
      identification, may be used as an internal control for both the amplification and
      hybridization steps; (ii) it simultaneously identifies M. tuberculosis complex,
      MAIS complex, and seven other mycobacterial species, even from mixed cultures;
      (iii) its mycobacterial DNA amplification ensures reliable results independent
      from the concentration of viable microorganisms; and (iv) it genotypically
      identifies M. kansasii and M. chelonae. In conclusion, even though INNO-LiPA
      Mycobacteria is considerably less easy to use than AccuProbe, requiring personnel
      skilled in molecular biology techniques, it represents an excellent approach for
      routine identification of frequently encountered mycobacteria.

PMID- 11526153
TI  - Use of serum immune complexes in a new test that accurately confirms early Lyme
      disease and active infection with Borrelia burgdorferi.
AB  - The present recommendation for serologic confirmation of Lyme disease (LD) calls
      for immunoblotting in support of positive or equivocal ELISA. Borrelia
      burgdorferi releases large quantities of proteins, suggesting that specific
      antibodies in serum might be trapped in immune complexes (ICs), rendering the
      antibodies undetectable by standard assays using unmodified serum. Production of
      ICs requires ongoing antigen production, so persistence of IC might be a marker
      of ongoing or persisting infection. We developed an immunoglobulin M (IgM)
      capture assay (EMIBA) measuring IC-derived IgM antibodies and tested it using
      three well-defined LD populations (from an academic LD referral center, a well
      described Centers for Disease Control and Prevention (CDC) serum bank, and a
      group of erythema migrans patients from whose skin lesions B. burgdorferi was
      grown) and controls (non-Lyme arthritis inflammatory joint disease, syphilis,
      multiple sclerosis, and nondisease subjects from a region where LD is endemic,
      perhaps the most relevant comparison group of all). Previous studies demonstrated
      that specific antigen-antibody complexes in the sera of patients with LD could be
      precipitated by polyethylene glycol and could then be disrupted with maintenance
      of the immunoreactivity of the released antibodies, that specific anti-B.
      burgdorferi IgM was concentrated in ICs, and that occasionally IgM to specific B.
      burgdorferi antigens was found in the IC but not in unprocessed serum. EMIBA
      compared favorably with commercial and CDC flagellin-enhanced enzyme-linked
      immunosorbent assays and other assays in confirming the diagnosis of LD. EMIBA
      confirmed early B. burgdorferi infection more accurately than the comparator
      assays. In addition, EMIBA more accurately differentiated seropositivity in
      patients with active ongoing infection from seroreactivity persisting long after
      clinically successful antibiotic therapy; i.e., EMIBA identified seroreactivity
      indicating a clinical circumstance requiring antibiotic therapy. Thus, EMIBA is a
      promising new assay for accurate serologic confirmation of early and/or active
      LD.

PMID- 11526155
TI  - Rapid method for detection of gram-positive and -negative bacteria in milk from
      cows with moderate or severe clinical mastitis.
AB  - A rapid method for demonstration of gram-positive and gram-negative bacteria in
      milk is described. The technique is based on dilution of the sample in a medium,
      followed by filtration through a porous polysulfone membrane with a pore size
      retaining and concentrating bacteria from the sample. The bacteria concentrated
      on the surface of the membrane are stained with a cationic dye (toluidine blue)
      that can be visualized by the naked eye. After staining, the membrane is treated
      with ethanol-acetic acid (pH 2.8 to 3.0), which causes decolorization of gram
      negative bacteria, whereas gram-positive bacteria retain the stain. The method
      does not require heat fixation, electrical power, microscopic examination, or
      specially trained personnel. The time needed to perform the test is approximately
      5 min. The technique was applied to artificially infected milk and milk from cows
      with moderate or severe clinical mastitis for detection and differentiation of
      bacteria. The sensitivity of the filtration method was 92 and 100% for gram
      positive and gram-negative bacteria, respectively, compared with traditional
      bacteriological culture of milk samples. The detection limit was 5 x 10(6) CFU/ml
      for Staphylococcus aureus and 1 x 10(6) CFU/ml for Escherichia coli in spiked
      milk samples. The overall specificity of the method was 86%. This diagnostic
      method can provide on-site guidance to the veterinarian to optimize use of
      antibiotics in mastitis therapy.

PMID- 11526156
TI  - Biofilm formation by Candida dubliniensis.
AB  - Candida dubliniensis is an opportunistic yeast closely related to Candida
      albicans that has been recently implicated in oropharyngeal candidiasis in human
      immunodeficiency virus-infected patients. Most manifestations of candidiasis are
      associated with biofilm formation, with cells in biofilms displaying properties
      dramatically different from free-living cells grown under normal laboratory
      conditions. Here, we report on the development of in vitro models of C.
      dubliniensis biofilms on the surfaces of biomaterials (polystyrene and acrylic)
      and on the characteristics associated with biofilm formation by this newly
      described species. Time course analysis using a formazan salt reduction assay to
      monitor metabolic activities of cells within the biofilm, together with
      microscopy studies, revealed that biofilm formation by C. dubliniensis occurred
      after initial focal adherence, followed by growth, proliferation, and maturation
      over 24 to 48 h. Serum and saliva preconditioning films enhanced the initial
      attachment of C. dubliniensis and subsequent biofilm formation. Scanning electron
      microscopy and confocal scanning laser microscopy were used to further
      characterize C. dubliniensis biofilms. Mature C. dubliniensis biofilms consisted
      of a dense network of yeasts cells and hyphal elements embedded within
      exopolymeric material. C. dubliniensis biofilms displayed spatial heterogeneity
      and an architecture showing microcolonies with ramifying water channels.
      Antifungal susceptibility testing demonstrated the increased resistance of
      sessile C. dubliniensis cells, including the type strain and eight different
      clinical isolates, against fluconazole and amphotericin B compared to their
      planktonic counterparts. C. dubliniensis biofilm formation may allow this species
      to maintain its ecological niche as a commensal and during infection with
      important clinical repercussions.

PMID- 11526157
TI  - Concomitant infection of enterotoxigenic Escherichia coli in an outbreak of
      cholera caused by Vibrio cholerae O1 and O139 in Ahmedabad, India.
AB  - In Ahmedabad, a major city in the state of Gujarat, India, an outbreak of acute
      secretory diarrhea caused by Vibrio cholerae O1 Ogawa El Tor, V. cholerae O139,
      and multiple serotypes of enterotoxigenic Escherichia coli (ETEC) occurred in
      January 2000. All of the representative V. cholerae O1 and O139 isolates examined
      harbored the ctxA gene (encoding the A subunit of cholera toxin) and the El Tor
      variant of the tcpA gene (encoding toxin-coregulated pilus). ETEC isolates of
      different serotypes were positive for the elt gene, encoding heat-labile
      enterotoxin. To further understand the molecular characteristics of the
      pathogens, representative isolates were examined by ribotyping and pulsed-field
      gel electrophoresis (PFGE). Ribotyping showed that the isolates of V. cholerae O1
      Ogawa exhibited a pattern identical to that of the prevailing clone of O1 in
      areas where cholera is endemic in India, and all of the O139 isolates were
      identical to the BII clone of V. cholerae O139. PFGE of the representative O1
      Ogawa isolates exhibited an identical pattern, comparable to the H pattern of the
      new clone of O1 reported in Calcutta, India. PFGE analysis of the V. cholerae
      O139 isolates showed identical patterns, but these differed from the PFGE
      patterns of O139 isolates reported during 1992 to 1997 in Calcutta. ETEC isolates
      showed genetic heterogeneity among isolates belonging to the same serotype,
      although the identical PFGE pattern was also observed among ETEC isolates of
      different serotypes. Antibiograms of the isolates were unusual, because all of
      the O139 isolates were resistant to nalidixic acid. Likewise, all of the E. coli
      isolates showed resistance to ciprofloxacin, norfloxacin, and nalidixic acid.
      This is a unique outbreak, and we believe that it is the first in which V.
      cholerae and ETEC were concomitantly involved.

PMID- 11526158
TI  - Evaluation of the VITEK 2 system for the identification and susceptibility
      testing of three species of nonfermenting gram-negative rods frequently isolated
      from clinical samples.
AB  - VITEK 2 is a new automatic system for the identification and susceptibility
      testing of the most clinically important bacteria. In the present study 198
      clinical isolates, including Pseudomonas aeruginosa (n = 146), Acinetobacter
      baumannii (n = 25), and Stenotrophomonas maltophilia (n = 27) were evaluated.
      Reference susceptibility testing of cefepime, cefotaxime, ceftazidime,
      ciprofloxacin, gentamicin, imipenem, meropenem, piperacillin, tobramycin,
      levofloxacin (only for P. aeruginosa), co-trimoxazole (only for S. maltophilia),
      and ampicillin-sulbactam and tetracycline (only for A. baumannii) was performed
      by microdilution (NCCLS guidelines). The VITEK 2 system correctly identified
      91.6, 100, and 76% of P. aeruginosa, S. maltophilia, and A. baumannii isolates,
      respectively, within 3 h. The respective percentages of essential agreement (to
      within 1 twofold dilution) for P. aeruginosa and A. baumannii were 89.0 and 88.0%
      (cefepime), 91.1 and 100% (cefotaxime), 95.2 and 96.0% (ceftazidime), 98.6 and
      100% (ciprofloxacin), 88.4 and 100% (gentamicin), 87.0 and 92.0% (imipenem), 85.0
      and 88.0% (meropenem), 84.2 and 96.0% (piperacillin), and 97.3 and 80%
      (tobramycin). The essential agreement for levofloxacin against P. aeruginosa was
      86.3%. The percentages of essential agreement for ampicillin-sulbactam and
      tetracycline against A. baumannii were 88.0 and 100%, respectively. Very major
      errors for P. aeruginosa (resistant by the reference method, susceptible with the
      VITEK 2 system [resistant to susceptible]) were noted for cefepime (0.7%),
      cefotaxime (0.7%), gentamicin (0.7%), imipenem (1.4%), levofloxacin (2.7%), and
      piperacillin (2.7%) and, for one strain of A. baumannii, for imipenem. Major
      errors (susceptible to resistant) were noted only for P. aeruginosa and cefepime
      (2.0%), ceftazidime (0.7%), and piperacillin (3.4%). Minor errors ranged from
      0.0% for piperacillin to 22.6% for cefotaxime against P. aeruginosa and from 0.0%
      for piperacillin and ciprofloxacin to 20.0% for cefepime against A. baumannii.
      The VITEK 2 system provided co-trimoxazole MICs only for S. maltophilia; no very
      major or major errors were obtained for co-trimoxazole against this species. It
      is concluded that the VITEK 2 system allows the rapid identification of S.
      maltophilia and most P. aeruginosa and A. baumannii isolates. The VITEK 2 system
      can perform reliable susceptibility testing of many of the antimicrobial agents
      used against P. aeruginosa and A. baumannii. It would be desirable if new
      versions of the VITEK 2 software were able to determine MICs and the
      corresponding clinical categories of agents active against S. maltophilia.

PMID- 11526159
TI  - International surveillance of bloodstream infections due to Candida species:
      frequency of occurrence and in vitro susceptibilities to fluconazole,
      ravuconazole, and voriconazole of isolates collected from 1997 through 1999 in
      the SENTRY antimicrobial surveillance program.
AB  - A surveillance program (SENTRY) of bloodstream infections (BSI) in the United
      States, Canada, Latin America, and Europe from 1997 through 1999 detected 1,184
      episodes of candidemia in 71 medical centers (32 in the United States, 23 in
      Europe, 9 in Latin America, and 7 in Canada). Overall, 55% of the yeast BSIs were
      due to Candida albicans, followed by Candida glabrata and Candida parapsilosis
      (15%), Candida tropicalis (9%), and miscellaneous Candida spp. (6%). In the
      United States, 45% of candidemias were due to non-C. albicans species. C.
      glabrata (21%) was the most common non-C. albicans species in the United States,
      and the proportion of non-C. albicans BSIs was highest in Latin America (55%). C.
      albicans accounted for 60% of BSI in Canada and 58% in Europe. C. parapsilosis
      was the most common non-C. albicans species in Latin America (25%), Canada (16%),
      and Europe (17%). Isolates of C. albicans, C. parapsilosis, and C. tropicalis
      were all highly susceptible to fluconazole (97 to 100% at < or =8 microg/ml).
      Likewise, 97 to 100% of these species were inhibited by < or =1 microg/ml of
      ravuconazole (concentration at which 50% were inhibited [MIC(50)], 0.007 to 0.03
      microg/ml) or voriconazole (MIC(50), 0.007 to 0.06 microg/ml). Both ravuconazole
      and voriconazole were significantly more active than fluconazole against C.
      glabrata (MIC(90)s of 0.5 to 1.0 microg/ml versus 16 to 32 microg/ml,
      respectively). A trend of increased susceptibility of C. glabrata to fluconazole
      was noted over the three-year period. The percentage of C. glabrata isolates
      susceptible to fluconazole increased from 48% in 1997 to 84% in 1999, and
      MIC(50)s decreased from 16 to 4 microg/ml. A similar trend was documented in both
      the Americas (57 to 84% susceptible) and Europe (22 to 80% susceptible). Some
      geographic differences in susceptibility to triazole were observed with Canadian
      isolates generally more susceptible than isolates from the United States and
      Europe. These observations suggest susceptibility patterns and trends among yeast
      isolates from BSI and raise additional questions that can be answered only by
      continued surveillance and clinical investigations of the type reported here
      (SENTRY Program).

PMID- 11526160
TI  - Variation in restriction fragment length polymorphisms among serial isolates from
      patients with Trichophyton rubrum infection.
AB  - Molecular genotyping of strains of Trichophyton rubrum and T. mentagrophytes from
      patients with onychomycosis of the toes was performed to ascertain whether the
      fungal genotype changes over the course of time as sequential samples were
      obtained from patients receiving antifungal therapy and during follow-up. Sixty
      six serial strains of T. rubrum and 11 strains of T. mentagrophytes were obtained
      from 20 patients (16 patients with T. rubrum, 4 with T. mentagrophytes) who were
      treated with oral antifungal therapy and observed over periods of up to 36
      months. These strains were screened for genetic variation by hybridization of
      EcoRI-digested genomic DNAs with a probe amplified from the small-subunit (18S)
      ribosomal DNA and adjacent internal transcribed spacer regions. A total of five
      restriction fragment length polymorphism (RFLP) types were observed among 66
      strains of T. rubrum. Two major RFLP types, differentiated by one band shift,
      represented 68% of the samples. None of the patients had a unique genotype. More
      than one RFLP type was often observed from a single patient (same nail) over a
      period of 1, 2, or 3 years, even in cases that did not appear cured at any time.
      Samples taken from different nails of the same patient had either the same or a
      different genotype. The genotypic variation did not correspond to any detectable
      phenotypic variation. Furthermore, no correlation was observed between the
      efficacy of the treatment administered and the genotype observed. While the DNA
      region studied distinguished among T. rubrum, T. mentagrophytes, and T.
      tonsurans, intraspecific RFLP variation was observed for T. rubrum and T.
      mentagrophytes strains. While independent multiple infection and coinhabitation
      of multiple strains may explain the presence of different genotypes in a nail,
      microevolutionary events such as rapid substrain shuffling, as seen in studies of
      repetitive regions in Candida species, may also produce the same result. The
      recovery of multiple strains during the course of sequential sampling of uncured
      patients further suggests that the typing system is not able to distinguish
      between relapse or reinfection, ongoing infection, and de novo infection.

PMID- 11526161
TI  - Detection of Ebola viral antigen by enzyme-linked immunosorbent assay using a
      novel monoclonal antibody to nucleoprotein.
AB  - With the increase in international traffic, the risk of introducing rare but
      severe infectious diseases like Ebola hemorrhagic fever is increasing all over
      the world. However, the system for the diagnosis of Ebola virus infection is
      available in a limited number of countries. In the present study, we developed an
      Ebola virus antigen-detection enzyme-linked immunosorbent assay (ELISA) system
      using a novel monoclonal antibody (MAb) to the nucleoprotein (NP). This antibody
      recognized an epitope defined by a 26-amino-acid stretch near the C terminus of
      NP. In a sandwich ELISA system with the MAb, as little as 30 ng of purified
      recombinant NP (rNP) was detected. Although this MAb was prepared by immunization
      with rNP of subtype Zaire, it also reacted to the corresponding region of NP
      derived from the Reston and Sudan subtypes. These results suggest that our ELISA
      system should work with three of four Ebola subtypes. Furthermore, our ELISA
      system detected the NP in subtype Reston-infected monkey specimens, while the
      background level in noninfected specimens was very low, suggesting the usefulness
      of the ELISA for laboratory diagnosis with clinical specimens.

PMID- 11526162
TI  - Evaluation of PCR-restriction profile analysis and IS2404 restriction fragment
      length polymorphism and amplified fragment length polymorphism fingerprinting for
      identification and typing of Mycobacterium ulcerans and M. marinum.
AB  - Mycobacterium ulcerans and M. marinum are emerging necrotizing mycobacterial
      pathogens that reside in common reservoirs of infection and exhibit striking
      pathophysiological similarities. Furthermore, the interspecific taxonomic
      relationship between the two species is not clear as a result of the very high
      phylogenetic relatedness (i.e., >99.8% 16S rRNA sequence similarity), in contrast
      to only 25 to 47% DNA relatedness. To help understand the genotypic affiliation
      between these two closely related species, we performed a comparative analysis
      including PCR restriction profile analysis (PRPA), IS2404 restriction fragment
      length polymorphism (RFLP), and amplified fragment length polymorphism (AFLP) on
      a set of M. ulcerans (n = 29) and M. marinum (n = 28) strains recovered from
      different geographic origins. PRPA was based on a triple restriction of the 3'
      end region of 16S rRNA, which differentiated M. ulcerans into three types;
      however, the technique could not distinguish M. marinum from M. ulcerans isolates
      originating from South America and Southeast Asia. RFLP based on IS2404 produced
      six M. ulcerans types related to six geographic regions and did not produce any
      band with M. marinum, confirming the previous findings of Chemlal et al. (K.
      Chemlal, K. DeRidder, P. A. Fonteyne, W. M. Meyers, J. Swings, and F. Portaels,
      Am. J. Trop. Med. Hyg. 64:270-273, 2001). AFLP analysis resulted in profiles
      which grouped M. ulcerans and M. marinum into two separate clusters. The
      numerical analysis also revealed subgroups among the M. marinum and M. ulcerans
      isolates. In conclusion, PRPA appears to provide a rapid method for
      differentiating the African M. ulcerans type from other geographical types but is
      unsuitable for interspecific differentiation of M. marinum and M. ulcerans. In
      comparison, whole- genome techniques such as IS 2404-RFLP and AFLP appear to be
      far more useful in discriminating between M. marinum and M. ulcerans, and may
      thus be promising molecular tools for the differential diagnosis of infections
      caused by these two species.

PMID- 11526163
TI  - Relevance of the number of positive bottles in determining clinical significance
      of coagulase-negative staphylococci in blood cultures.
AB  - Coagulase-negative staphylococci (CNS) are the most commonly isolated
      contaminants from blood cultures, yet they frequently cause true infections.
      Determining the clinical significance of CNS is difficult, and clinicians often
      consider the number of positive bottles within a set of blood culture bottles in
      their assessment. Therefore, in three separate studies, we counted the number of
      positive bottles within blood culture sets comprising two, three, or four bottles
      in order to predict whether or not CNS were clinically significant isolates (CSI)
      in adult patients with suspected sepsis. Each culture was evaluated by
      independent, published clinical criteria to determine its clinical importance. Of
      486 positive sets that included two adequately filled bottles, 127 (26%) CNS were
      CSI, 329 (67%) were contaminants, and 30 (6%) were indeterminate as a cause of
      sepsis. Among CSI, 39 and 61% were isolated from one and two bottles,
      respectively. The positive predictive value for sepsis was 18% when one bottle
      was positive and 37% when both bottles were positive. Of 235 positive sets that
      included three adequately filled bottles, 81 (34%) were CSI, 109 (46%) were
      contaminants, and 45 (19%) were indeterminate as a cause of sepsis. Of CSI, 43,
      38, and 19% were found in one, two, and three bottles, respectively. The positive
      predictive value for sepsis was 28, 52, and 30% when one, two and three bottles
      were positive. Of 303 positive blood culture sets that included four adequately
      filled bottles, 64 (21%) were considered CSI, 197 (65%) were contaminants, and 42
      (14%) were indeterminate as a cause of sepsis. Of CSI, 27, 28, 19, and 27% were
      found in one, two, three, and four bottles, respectively. The positive predictive
      value for sepsis was 11, 30, 34, and 37% when one, two, three, and four bottles
      were positive. We conclude that the number of culture bottles positive in a given
      culture set cannot reliably predict the clinical significance of the CNS isolated
      and, therefore, should not be used as a criterion for determining whether or not
      an isolate represents true infection or contamination.

PMID- 11526164
TI  - Molecular identification of microorganisms from endodontic infections.
AB  - A relatively wide range of bacteria have been isolated from root canals using
      standard culture techniques. However, only 50% of the bacteria in the oral cavity
      are cultivable (S. S. Socransky et al., Arch. Oral Biol. 8:278-280, 1963); hence,
      bacterial diversity in endodontic infections is underestimated. This study used a
      PCR-based 16S rRNA gene assay, followed by cloning and sequencing of 16S rRNA
      amplicons from a small subset of samples to assess the diversity of bacteria
      present in infected root canals. A total of 41 clinical samples from 15 de novo
      and 26 refractory cases of endodontic infections were assessed. Of these samples,
      44% were positive by culture and 68% were positive by PCR. Eight samples were
      selected for further analysis. Of these, the two de novo cases yielded sequences
      related to those of the genera Enterococcus, Lactobacillus, Propionibacterium,
      and Streptococcus and two clones were related to previously uncultivated
      bacteria, while the sinus-associated, de novo case yielded sequences related to
      those of the genera Lactobacillus, Pantoea, Prevotella, and Selenomonas. The five
      refractory cases produced clones which were related to the genera Capnocytophaga,
      Cytophaga, Dialister, Eubacterium, Fusobacterium, Gemella, Mogibacterium,
      Peptostreptococcus, Prevotella, Propionibacterium, Selenomonas, Solobacterium,
      Streptococcus, and Veillonella and two clones representing previously
      uncultivated bacteria. The phylogenetic positions of several clones associated
      with the Clostridiaceae and Sporomusa subgroups of the Firmicutes grouping are
      also shown. This study demonstrates that molecular techniques can detect the
      presence of bacteria in endodontic infections when culture techniques yield a
      negative result and can be used to identify a wider range of endodontic-infection
      related bacteria including the presence of previously unidentified or
      unculturable bacteria.

PMID- 11526165
TI  - Genetic and phenotypic features of Streptococcus pyogenes strains isolated in
      Brazil that harbor new emm sequences.
AB  - In the present study, 37 group A Streptococcus (GAS) strains belonging to 13 new
      emm sequence types identified among GAS strains randomly isolated in Brazil were
      characterized by using phenotypic and genotypic methods. The new types were
      designated st204, st211, st213, st809, st833, st854, st2904, st2911, st2917,
      st2926, st3757, st3765, and st6735. All isolates were susceptible to the
      antimicrobial agents tested, except to tetracycline. They all carried the speB
      gene, and 94.6% produced detectable SpeB. Most strains belonging to a given emm
      type had similar or highly related pulsed-field gel electrophoresis profiles that
      were distinct from profiles of strains of another type. The other characteristics
      were variable from isolate to isolate, although some associations were
      consistently found within some emm types. Unlike the other isolates, all type
      st213 isolates were speA positive and produced SpeA. Strains belonging to st3765
      were T6 and opacity factor (OF) negative. Individual isolates within OF-positive
      emm types were associated with unique sof gene sequence types, while OF-negative
      isolates were sof negative by PCR. This report provides information on new emm
      sequence types first detected in GAS isolates from a geographic area not
      extensively surveyed. Such data can contribute to a better understanding of the
      local and global dynamics of GAS populations and of the epidemiological aspects
      of GAS infections occurring in tropical regions.

PMID- 11526166
TI  - Antifungal effects of lysozyme and lactoferrin against genetically similar,
      sequential Candida albicans isolates from a human immunodeficiency virus-infected
      southern Chinese cohort.
AB  - A variety of innate defense factors in saliva such as lysozyme and lactoferrin
      contribute to mucosal protection and modulate Candida populations in the oral
      cavity. It is also known that in human immunodeficiency virus (HIV)-infected
      individuals significant variations in the concentrations of lysozyme and
      lactoferrin in saliva occur during disease progression. Therefore, the aim of
      this study was to determine the in vitro susceptibility to human lactoferrin and
      hen egg white lysozyme of genotypically similar oral Candida albicans isolates
      obtained from six HIV-infected ethnic Chinese during sequential visits over a 12
      month period. The similarity of the genotypes (50 in total) was evaluated using a
      randomly amplified polymorphic DNA assay. A blastospore viability assay was
      performed to evaluate the sensitivity of the organisms to lysozyme and
      lactoferrin. Exposure to physiological concentrations of either lysozyme (30
      microg/ml) or lactoferrin (20 microg/ml) caused a rapid loss of viability among
      all isolates to a varying extent. None of the sequential C. albicans isolates
      demonstrated significant differences in sensitivity to either protein from one
      visit to the next; similar results were noted when the different genotypes from
      the same individual were compared. On Spearman correlation analysis of two
      genotypes that were sequentially isolated from a single patient, a significant
      negative correlation between lysozyme (r = -0.88; P < 0.02) (but not lactoferrin)
      resistance and the duration of HIV disease was seen. These results imply that a
      minority of C. albicans isolates that persist intraorally in individuals with HIV
      disease develop progressive resistance to innate salivary antifungal defenses
      such as lysozyme, possibly as an adaptive response. However, the vast majority of
      the Candida isolates appear to succumb to these nonspecific host immune mediators
      abundantly present in the oral environment.

PMID- 11526167
TI  - Evaluation of recombinant Leptospira antigen-based enzyme-linked immunosorbent
      assays for the serodiagnosis of leptospirosis.
AB  - There is an urgent need for development of new serodiagnostic strategies for
      leptospirosis, an emerging zoonosis with worldwide distribution. We have
      evaluated the diagnostic utility of five recombinant antigens in enzyme-linked
      immunosorbent assays (ELISAs) for serodiagnosis of leptospirosis. Sera from 50
      healthy residents of a high-incidence region were used to determine cutoff values
      for 96% specificity. In paired sera from 50 cases of leptospirosis confirmed by
      the microscopic agglutination test, immunoglobulin G (IgG) but not IgM reacted
      with the recombinant leptospiral proteins. The recombinant LipL32 IgG ELISA had
      the highest sensitivities in the acute (56%) and convalescent (94%) phases of
      leptospirosis. ELISAs based on recombinant OmpL1, LipL41, and Hsp58 had
      sensitivities of 16, 24, and 18% during the acute phase and 72, 44, and 32%
      during convalescence, respectively. Compared to sera from healthy individuals,
      patient sera did not react significantly with recombinant LipL36 (P > 0.05).
      Recombinant LipL32 IgG ELISA demonstrated 95% specificity among 100 healthy
      individuals, and specificities ranging from 90 to 97% among 30 dengue patients,
      30 hepatitis patients, and 16 patients with diseases initially thought to be
      leptospirosis. Among 39 Venereal Disease Research Laboratory test-positive
      individuals and 30 Lyme disease patients, 13 and 23% of sera, respectively,
      reacted positively with the rLipL32 antigen. These findings indicate that rLipL32
      may be an useful antigen for the serodiagnosis of leptospirosis.

PMID- 11526168
TI  - Identification of novel Helicobacter species in pig stomachs by PCR and partial
      sequencing.
AB  - Evidence of infection with Helicobacter species in pig stomach was investigated
      by the use of a PCR with Helicobacter genus-specific primers. Forty pig stomachs,
      each of four different ulcer lesion grades, 0, 1, 2, and 3 in the pars esophagea
      area, were collected from a slaughterhouse in Minnesota. Of 160 stomach samples
      examined, 102 (63.8%) were positive by the PCR assay. The 40 samples each of
      lesion grades 0, 1, 2, and 3 showed 22.5, 52.5, 85.0, and 95.0% PCR-positive
      results, respectively. There was a significant trend (P < or = 0.01) in the
      proportions of PCR-positive cases relative to severity of the lesion. About 80%
      of the 16S rRNA gene was amplified, and PCR-restriction fragment length
      polymorphism (RFLP) patterns were analyzed. Of 102 PCR-positive samples, the PCR
      RFLP patterns resulted in four different types, 32 samples being classified into
      type MN 1, 16 samples into type MN 2, 43 samples into type MN 3, and 11 samples
      into type MN 4. When the sequences of each RFLP type were compared to those
      reported in databases by using BLAST software, types MN 1, MN 2, MN 3, and MN 4
      showed homologies of 97.3, 95.4, 96.7, and 99.5% with the 16S ribosomal DNA of
      Helicobacter flexispira taxon 3, Helicobacter sp. strains MIT 94-022 and MZ
      640285, and Helicobacter suis, respectively. None of the 102 samples positive for
      the Helicobacter genus were positive with a primer set specific for Helicobacter
      pylori. Attempts to culture the organisms from selected stomachs in vitro were
      unsuccessful.

PMID- 11526169
TI  - Pneumococcal carriage in children in The Netherlands: a molecular epidemiological
      study.
AB  - In 1999, Engelen and coworkers investigated colonization in Amsterdam among 259
      children attending 16 day-care centers (DCCs) and among 276 children who did not
      attend day-care centers (NDCCs). A 1.6- to 3.4-fold increased risk for
      nasopharyngeal colonization was observed in children attending DCCs compared with
      NDCC children, while no difference in antibiotic resistance was found between
      groups. The serotype and genotype distributions of 305 nasopharyngeal
      Streptococcus pneumoniae isolates of the latter study were investigated. The
      predominant serotypes in both the DCC and the NDCC groups included 19F (19 and
      18%, respectively), 6B (14 and 16%, respectively), 6A (13 and 7%, respectively),
      23F (9 and 7%, respectively), and 9V (7 and 7%, respectively). The theoretical
      vaccine coverage of the 7-valent conjugate vaccine was 59% for the DCC children
      and 56% for the NDCC group. Genetic analysis of the pneumococcal isolates
      revealed 75% clustering among pneumococci isolated from DCC attendees versus 50%
      among the NDCC children. The average pneumococcal cluster size in the DCC group
      was 3.8 and 4.6 isolates for two respective sample dates (range, 2 to 13 isolates
      per cluster), while the average cluster size for the NDCC group was 3.0 (range, 2
      to 6 isolates per cluster). Similar to observations made in other countries,
      these results indicate a higher risk for horizontal spread of pneumococci in
      Dutch DCCs than in the general population. This study emphasizes the importance
      of molecular epidemiological monitoring before, during, and after implementation
      of pneumococcal conjugate vaccination in national vaccination programs for
      children.

PMID- 11526170
TI  - Six-year study of the incidence of herpes in genital and nongenital cultures in a
      central Kentucky medical center patient population.
AB  - Herpes infections are among the most common sexually transmitted diseases and are
      the most common cause of genital ulcer disease in the United States. This study
      addresses the changing distribution of herpes simplex virus type 1 (HSV-1) and
      HSV-2 in patients presenting for evaluation of herpetic infections. Viral culture
      results from the University of Kentucky Clinical Microbiology Laboratory were
      reviewed for a 6-year period (1994 through 1999). Data were collected on patient
      sex, site of culture, and culture result. These data were analyzed statistically
      to identify yearly trends. Of the 4,498 cultures analyzed, nearly equal
      proportions of HSV-1 (13.3%) and HSV-2 (12.0%) were detected for an overall
      culture positivity rate of 25.3%. Approximately two-thirds of all positive
      cultures were from women. Although HSV-2 remained the predominant type of genital
      herpes, over the 6-year span of this study, there was a trend toward increasing
      proportions of HSV-1 genitalis, with 31.8% of male patients and 44.8% of female
      patients demonstrating HSV-1 genitalis by 1999. The majority of patients with HSV
      in nongenital sites grew HSV-1. Although there was significant yearly variation,
      HSV-2 was isolated from only 9.4% of patients with nongenital HSV for the entire
      6-year period. This study therefore concludes that HSV-2 remains primarily a
      genital pathogen, while HSV-1 is taking on an increasingly important role in
      causing genital ulcer disease in addition to being the primary nongenital HSV.

PMID- 11526171
TI  - Determination of Enterococcus faecalis groESL full-length sequence and
      application for species identification.
AB  - Amplification of the partial Cpn60 (or GroEL) gene segment has been used for
      identification of many bacteria, including Enterococcus species. To obtain more
      sequence data from groESL genes of Enterococcus faecalis, the full-length
      sequence of the E. faecalis groESL genes containing groES (285 bp), spacer (57
      bp), and groEL (1,626 bp) was determined. A database search of GenBank revealed
      that the deduced E. faecalis GroES and GroEL proteins show significant homology
      to the GroES and GroEL proteins of other bacteria. The GroEL (groEL) of E.
      faecalis had the highest identity with Streptococcus pneumoniae (81.8% amino acid
      sequence identity and 73.0% nucleotide sequence identity), followed by
      Lactococcus zeae, while GroES (groES) had 60.2% (64.6%) identity with
      Lactobacillus zeae and 58.5% (66.2%) identity with Lactococcus lactis, followed
      by 57.0% (65.5%) identity with Bacillus subtilis. Based on the groES sequence, an
      E. faecalis-specific PCR assay was developed, and this PCR assay was positive for
      all the E. faecalis strains tested. Dot blot hybridization using either groES or
      groEL as the probe distinguished E. faecalis clearly from other species,
      indicating that both genes can be used as suitable targets for E. faecalis
      identification. Moreover, broad-range PCR-restriction fragment length
      polymorphism of groESL was designed to differentiate eight commonly encountered
      Enterococcus species. The Enterococcus species of reference strains could be
      easily differentiated on the basis of restriction patterns produced by HaeIII and
      RsaI. The DNA-based assays developed in this study provide an alternative to
      currently used methods of identification for clinically important enterococcal
      species.

PMID- 11526172
TI  - Multiplex PCR protocol for the diagnosis of staphylococcal infection.
AB  - We report the development of a multiplex PCR protocol for the diagnosis of
      staphylococcal infection. The protocol was designed to (i) detect any
      staphylococcal species to the exclusion of other bacterial pathogens (based on
      primers corresponding to Staphylococcus-specific regions of the 16S rRNA genes),
      (ii) distinguish between S. aureus and the coagulase-negative staphylococci (CNS)
      (based on amplification of the S. aureus-specific clfA gene), and (iii) provide
      an indication of the likelihood that the staphylococci present in the specimen
      are resistant to oxacillin (based on amplification of the mecA gene). The
      expected fragments were amplified from each of 60 staphylococcal isolates (13
      oxacillin-resistant S. aureus isolates, 23 oxacillin-sensitive S. aureus
      isolates, 17 oxacillin-resistant CNS, and 7 oxacillin-sensitive CNS). No
      amplification products were observed with template DNA from nonstaphylococcal
      species, and the efficiency of amplification of staphylococcal targets was not
      adversely affected by the presence of DNA from other bacterial species in the
      same sample. The utility of the protocol for the analysis of clinical samples was
      verified by analysis of aliquots taken directly from BacT/Alert blood culture
      bottles. Of 77 blood cultures tested, only 7 yielded results inconsistent with
      those of conventional methods of diagnosis and susceptibility testing. Of those,
      one was identified as a CNS species by PCR and S. aureus by conventional methods.
      We also identified two isolates that were mecA positive but were oxacillin
      sensitive according to conventional methods. The other four samples failed to
      yield any amplification product even with a control set of primers corresponding
      to a conserved region of the eubacterial rRNA genes.

PMID- 11526173
TI  - Spread of drug-resistant pulmonary tuberculosis in Estonia.
AB  - Restriction fragment length polymorphism (RFLP) analysis of 209 Mycobacterium
      tuberculosis clinical isolates obtained from newly detected pulmonary
      tuberculosis patients (151 male and 58 female; mean age, 41 years) in Estonia
      during 1994 showed that 61 isolates (29%) belonged to a genetically closely
      related group of isolates, family A, with a predominant IS6110 banding pattern.
      These strains shared the majority of their IS6110 DNA-containing restriction
      fragments, representing a predominant banding pattern (similarity, >65%). This
      family A comprised 12 clusters of identical isolates, and the largest cluster
      comprised 10 strains. The majority (87.5%) of all multidrug-resistant (MDR)
      isolates, 67.2% of all isolates with any drug resistance, but only 12% of the
      fully susceptible isolates of M. tuberculosis belonged to family A. These strains
      were confirmed by spoligotyping as members of the Beijing genotype family. The
      spread of Beijing genotype MDR M. tuberculosis strains was also frequently seen
      in 1997 to 1999. The members of this homogenous group of drug-resistant M.
      tuberculosis strains have contributed substantially to the continual emergence of
      drug-resistant tuberculosis all over Estonia.

PMID- 11526174
TI  - Sequence typing confirms that Campylobacter jejuni strains associated with
      Guillain-Barre and Miller-Fisher syndromes are of diverse genetic lineage,
      serotype, and flagella type.
AB  - Guillain-Barre syndrome (GBS) and Miller-Fisher syndrome (MFS) are correlated
      with prior infection by Campylobacter jejuni in up to 40% of cases. Nucleotide
      sequence-based typing of 25 C. jejuni isolates associated with neuropathy
      permitted robust comparisons with equivalent data from approximately 800 C.
      jejuni isolates not associated with neuropathy. A total of 13 genetic lineages
      and 20 flaA short variable region nucleotide sequences were present among the 25
      isolates. A minority of isolates (4 of 25) had the flaA short variable region
      nucleotide sequences that were previously proposed as a marker for GBS-associated
      isolates. These 4 isolates probably represented the Penner serotype 19 lineage,
      which has been proposed to have an association with GBS.

PMID- 11526175
TI  - Detection of rpoB mutations in Mycobacterium tuberculosis by biprobe analysis.
AB  - A biprobe assay utilizing LightCycler technology was developed to detect rifampin
      resistance-associated gene mutations in the Mycobacterium tuberculosis rpoB gene.
      Three biprobes detected all mutations present in the 46 rifampin-resistant
      isolates. Wild-type sequences were correctly identified in each case. The method
      was reproducible, accurate, and easy to use.

PMID- 11526176
TI  - Existence of hepatitis C virus in Culex quinquefasciatus after ingestion of
      infected blood: experimental approach to evaluating transmission by mosquitoes.
AB  - We used PCR to detect hepatitis C virus (HCV) RNA among supernatants of ground
      Culex quinquefasciatus mosquitoes that (i) had been fed HCV-positive blood, (ii)
      had been intrathoracically inoculated with HCV-positive blood, or (iii) were from
      homes of hepatitis C patients. HCV RNA was detectable under all three conditions,
      but it did not replicate in mosquitoes and was not detectably transmitted during
      feeding.

PMID- 11526177
TI  - Isolation and characterization of a species-specific DNA fragment for
      identification of Candida (Torulopsis) glabrata by PCR.
AB  - A PCR specific for Candida glabrata that amplifies a mitochondrial rRNA gene
      fragment was developed by analysis of C. glabrata-specific agarose gel bands,
      which were generated by arbitrarily primed PCR. The expected PCR product was
      successfully amplified with genomic DNA from 95 C. glabrata isolates but not from
      a number of other fungal isolates.

PMID- 11526178
TI  - Survival of some medically important fungi on hospital fabrics and plastics.
AB  - Tests of the survival of Candida spp., Aspergillus spp., a Fusarium sp., a Mucor
      sp., and a Paecilomyces sp. on hospital fabrics and plastics indicated that
      viability was variable, with most fungi surviving at least 1 day but many living
      for weeks. These findings reinforce the need for appropriate disinfection and
      conscientious contact control precautions.

PMID- 11526179
TI  - Discrimination between Candida albicans and other pathogenic species of the genus
      Candida by their differential sensitivities to toxins of a panel of killer
      yeasts.
AB  - The differential sensitivities to toxins produced by a short panel of four killer
      yeasts allowed discrimination between 91 strains of the yeast Candida albicans
      and 223 non-C. albicans Candida strains. One hundred percent of C. albicans
      isolates exhibited negative results to the toxin panel, while 100% of non-C.
      albicans cultures gave well-defined and reproducible positive results to at least
      one of the four killer toxins. Among C. albicans strains only 96 and 87% gave
      germ tube (GT)- and chlamydospore-positive results, respectively. In addition a
      few GT-false-positive strains were detected among non-C. albicans isolates.
      Susceptibility to the toxin panel is apparently expressed more consistently than
      either GT or chlamydospore production and may constitute a promising basis for a
      new simple and easy-to-use procedure for routine discrimination between the
      species C. albicans and other species of the genus Candida.

PMID- 11526180
TI  - Cryptococcus neoformans var. neoformans (serotype D) strains are more susceptible
      to heat than C. neoformans var. grubii (serotype A) strains.
AB  - Cryptococcus neoformans var. neoformans (serotype D) and C. neoformans var.
      grubii (serotype A) differ in geographic prevalence and dermatotropism, with C.
      neoformans var. neoformans strains being more prevalent among isolates from
      temperate countries as well as from skin infections. Analysis of 19 strains from
      each serotype revealed wide variation in thermal susceptibility, with C.
      neoformans var. neoformans strains being more susceptible, on average, to heat
      killing. The results suggest a consistent explanation for the geographic
      differences between serotype A and D strains and for the dermatotropism of
      serotype D strains.

PMID- 11526181
TI  - Cysticercus antigens in cerebrospinal fluid samples from patients with
      neurocysticercosis.
AB  - Antigens were detected in cerebrospinal fluid (CSF) samples from patients with
      neurocysticercosis (NC) by enzyme-linked immunosorbent assay (ELISA) using
      polyclonal sera of rabbit anti-Taenia solium cysticerci (anti-Tso) and anti-
      Taenia crassiceps cysticerci vesicular fluid (anti-Tcra or anti-Tcra <30 kDa). A
      group of NC patients (n = 174) were studied (NC), including 40 patients in
      different phases of the disease. ELISAs carried out with the anti-Tso, anti-Tcra,
      and anti-Tcra <30 kDa showed sensitivities of 81.2, 90, and 95.8% and
      specificities of 82, 98, and 100%, respectively. The 14- and 18-kDa low-molecular
      weight peptides were only detected in CSF samples from patients with NC by
      immunoblotting with anti-Tso and anti-Tcra sera. Because of the importance of the
      diagnosis and prognosis of cysticercosis, the detection of antigens may
      contribute as an additional marker to the study and clarification of the parasite
      host relationship.

PMID- 11526182
TI  - Identification of Streptococcus pneumoniae revisited.
AB  - The sensitivities and specificities of several different diagnostic assays for
      Streptococcus pneumoniae were assessed using 99 clinical isolates of S.
      pneumoniae and 101 viridans streptococci and were as follows: Pneumoslide, 99 and
      87%, respectively; Directigen, 100 and 85%, respectively; Phadebact, 100 and 98%,
      respectively; deoxycholate drop test, 99 and 98%, respectively; deoxycholate tube
      test, 100 and 99%, respectively; optochin, 99 and 98%, respectively; and Gram
      Positive Identification Card, 90 and 96%, respectively. Identification of
      clinical isolates of S. pneumoniae should be confirmed using one or more
      diagnostic assays with well-documented high (e.g., > or =95%) sensitivities and
      specificities.

PMID- 11526183
TI  - Prevalence of molecular types and mecA gene carriage of coagulase-negative
      Staphylococci in a neonatal intensive care unit: relation to nosocomial
      septicemia.
AB  - Molecular typing of isolates revealed that neonatal coagulase-negative
      staphylococcal (CONS) septicemia is most frequently caused by predominant,
      antibiotic-resistant CONS types, which are widely distributed among both neonates
      and staff of the neonatal unit, suggesting cross-contamination. Therefore,
      infection control measures may be valuable in the prevention of this common
      nosocomial septicemia.

PMID- 11526184
TI  - Heteroresistance to vancomycin in Enterococcus faecium.
AB  - This study presents the first report of vancomycin heteroresistance in an
      Enterococcus faecium isolate from a patient. The original isolate was susceptible
      in vitro to vancomycin. E-tests showed growth of subcolonies in a zone of
      inhibition with a vancomycin MIC of >256 microg/ml. Both the susceptible and
      resistant colonies were from the same strain as determined by PFGE, and both
      contained the vanA gene as determined by PCR.

PMID- 11526185
TI  - Application of PCR to distinguish common species of dermatophytes.
AB  - This report describes the application of PCR fingerprinting for the
      identification of species and varieties of common dermatophytes and related fungi
      utilizing as a single primer the simple repetitive oligonucleotide (GACA)(4). The
      primer was able to amplify all the strains, producing species-specific profiles
      for Microsporum canis, Microsporum gypseum, Trichophyton rubrum, Trichophyton
      ajelloi, and Epidermophyton floccosum. Intraspecific variability was not observed
      for these species. Instead, three different profiles were observed in the
      Trichophyton mentagrophytes group.

PMID- 11526186
TI  - First report of human infection due to the fungus Triadelphia pulvinata.
AB  - Triadelphia pulvinata, a soil hyphomycete, was found to be the cause of
      eczematoid, scaly, grey lesions on the skin of both eyelids of a 30-year-old
      Indian male living in Saudi Arabia. Repeated KOH preparations of the skin
      scrapings showed presence of sclerotic, branched, septate hyphae. When cultured,
      skin scrapings from the lesion grew the dematiaceous fungus T. pulvinata.
      Treatment with topical clotrimazole cured the infection, and no recurrence of the
      infection was noted in a 5-year follow-up.

PMID- 11526188
TI  - Contamination of catheter-drawn blood cultures.
AB  - To assess the risk of contamination, we reviewed retrospectively 1,408 matched
      pairs of simultaneous catheter-drawn and venipuncture blood cultures. Catheter
      drawn cultures were equally likely to be truly positive (14.4 versus 13.7%) but
      more likely to be contaminated (3.8 versus 1.8% [P = 0.001]). Direct venipuncture
      cultures are preferred.

PMID- 11526187
TI  - Multicenter proficiency testing of nucleic acid amplification methods for the
      detection of enteroviruses.
AB  - A multicenter study of molecular detection of enteroviruses was conducted using a
      proficiency panel. Of 70 data sets, 46 (66%) reported correct results for samples
      containing at least 1 50% infective dose per ml and for negative samples.
      Variation in performance between laboratories demonstrates the need for ongoing
      quality control.

PMID- 11526189
TI  - Diversity of Babesia Infecting European sheep ticks (Ixodes ricinus).
AB  - Questing Ixodes ricinus (Acari: Ixodidae) adult and nymphal ticks collected in
      various parts of Slovenia were tested for the presence of babesial parasites with
      a PCR assay based on the nuclear small subunit rRNA gene (nss-ribosomal DNA
      [rDNA]). Thirteen of 135 ticks were found to contain babesial DNA. Sequence
      determination and analysis of amplified portions of nss-rDNA revealed their
      identity with Babesia microti and a high degree of homology with Babesia
      odocoilei and Babesia divergens. The results of this study represent the first
      genetic evidence of B. microti and B. divergens-like parasites in I. ricinus
      ticks in Europe.

PMID- 11526190
TI  - Molecular typing of the etiologic agent of human granulocytic ehrlichiosis.
AB  - The p44 gene of the agent of human granulocytic ehrlichiosis (aoHGE) encodes a 44
      kDa major outer surface protein. A technique was developed for the typing of the
      aoHGE based on the PCR amplification of the p44 gene followed by a multiple
      restriction digest with HindIII, EcoRV, and AspI to generate restriction fragment
      length polymorphism patterns. Twenty-four samples of the aoHGE were collected
      from geographically dispersed sites in the United States and included isolates
      from humans, equines, canines, small mammals, and ticks. Six granulocytic
      ehrlichiosis (GE) types were identified. The GE typing method is relatively
      simple to perform, is reproducible, and is able to differentiate among the
      various isolates of granulocytic ehrlichiae in the United States. These
      characteristics suggest that this GE typing method may be an important
      epizootiological and epidemiological tool.

PMID- 11526191
TI  - Colorimetric assay for antifungal susceptibility testing of Aspergillus species.
AB  - A colorimetric assay for antifungal susceptibility testing of Aspergillus species
      (Aspergillus fumigatus, Aspergillus flavus, Aspergillus terreus, Aspergillus
      nidulans, and Aspergillus ustus) is described based on the reduction of the
      tetrazolium salt 2,3-bis(2-methoxy-4-nitro-5-[(sulphenylamino)carbonyl]-2H
      tetrazolium-hydroxide (XTT) in the presence of menadione as an electron-coupling
      agent. The combination of 200 microg of XTT/ml with 25 microM menadione resulted
      in a high production of formazan within 2 h of exposure, allowing the detection
      of hyphae formed by low inocula of 10(2) CFU/ml after 24 h of incubation. Under
      these settings, the formazan production correlated linearly with the fungal
      biomass and less-variable concentration effect curves for amphotericin B and
      itraconazole were obtained.

PMID- 11526192
TI  - Murine monoclonal antibodies against Escherichia coli O4 lipopolysaccharide and
      H5 flagellin.
AB  - Two murine monoclonal antibodies (MAb), 2C5-F10 and 8D1-H10, reactive with
      Escherichia coli O4 and H5 antigens, respectively, were generated and
      characterized. Enzyme immunoassays and immunoblots demonstrated that MAb 2C5-F10
      reacted specifically with lipopolysaccharide O antigen of E. coli O4 isolates,
      while MAb 8D1-H10 reacted with E. coli strains expressing H5 flagella.

PMID- 11526193
TI  - Hemorrhagic fever with renal syndrome: diagnostic problems with a known disease.
AB  - Hemorrhagic fever with renal syndrome (HFRS), caused by different hantaviruses,
      is a distinct clinical syndrome endemic in several parts of Asia and Europe.
      However, the clinical picture can sometimes be indistinguishable from that of
      other infectious or noninfectious diseases. In this report we describe a clinical
      case, which is a rare occurrence but is a prime example of the difficulties in
      the diagnosis of HFRS in areas with a low prevalence of the disease.

PMID- 11526194
TI  - Native valve endocarditis due to Bartonella henselae in a middle-aged human
      immunodeficiency virus-negative woman.
AB  - We report the case of a human immunodeficiency virus-negative woman who developed
      native valve endocarditis of the aortic valve due to Bartonell henselae
      infection. The diagnosis was established using serology and PCR analysis of
      excised aortic valve tissue.

PMID- 11526195
TI  - Peritoneal dialysis-associated peritonitis caused by Dermabacter hominis.
AB  - Dermabacter hominis was the cause of a peritoneal dialysis-associated
      peritonitis. D. hominis was identified by phenotypic criteria and by sequencing
      the 16S rRNA gene. Clinical cure was achieved with cefuroxime treatment despite
      the isolate's reduced susceptibility to this drug (MIC, 12 mg/liter) on in vitro
      testing. The successful treatment was probably due to the high concentrations
      attained by intraperitoneal administration of the drug.

PMID- 11526196
TI  - The mouse Na+-K+-ATPase gamma-subunit gene (Fxyd2) encodes three developmentally
      regulated transcripts.
AB  - The Na(+)-K(+)-ATPase is understood to function as a hetero-oligomer of alpha-
      and beta-subunits, but a third subunit, gamma, has been proposed to influence the
      enzyme's catalytic function. Recently, two variants of the gamma-subunit have
      been described in kidney, raising the possibility of multiple gamma-subunits with
      diverse functions. We now report the cloning and sequencing of the mouse gamma
      subunit gene (Fxyd2). Analysis of the structure of the gene shows that it encodes
      three mRNAs that have distinct NH(2)-terminal (extracellular) encoding sequences
      but common transmembrane and COOH-terminal-encoding sequences resulting from
      differential splicing and, probably, alternate promoter usage. The three mRNAs
      have tissue-specific expression patterns. The existence of three different
      extracellular domains of the gamma-variants and how they may interact with the
      sodium pump to alter its cation transport properties must now be taken into
      account for future understanding of the modulation of the Na(+)-K(+)-ATPase by
      its gamma-subunit.

PMID- 11526197
TI  - New Dyscalc loci for myocardial cell necrosis and calcification (dystrophic
      cardiac calcinosis) in mice.
AB  - Dystrophic cardiac calcinosis (DCC) occurs among certain inbred strains of mice
      and involves necrosis and subsequent calcification as response of myocardial
      tissue to injury. Using a complete linkage map approach, we investigated the
      genetics of DCC in an F(2) intercross of resistant C57BL/6J and susceptible
      C3H/HeJ inbred strains and identified previously a major predisposing
      quantitative trait locus (QTL), Dyscalc1, on proximal chromosome 7. Analysis of
      inheritance suggested, however, that DCC is influenced by additional modifier
      QTL, which have as yet not been mapped. Here, we report the identification by
      composite interval mapping of the DCC loci Dyscalc2, Dyscalc3, and Dyscalc4 on
      chromosomes 4, 12 and 14, respectively. Together, the four Dyscalc loci explained
      47% of the phenotypic variance of DCC, which was induced by a high-fat diet.
      Additive epistasis between Dyscalc1 and Dyscalc2 enhanced DCC. Examining
      recombinant inbred strains, we propose a 10-cM interval containing Dyscalc1 and
      discuss potential candidate genes.

PMID- 11526198
TI  - Identification of genomic regions controlling plasma FSH concentrations in
      Meishan-White Composite boars.
AB  - The Chinese Meishan (ME) breed of pig is unique for many reproductive traits.
      Compared with Western breeds of swine, ME females reach puberty earlier, ovulate
      more ova per estrus, and have greater uterine capacity, while intact males
      (boars) have smaller testes and extremely elevated plasma levels of pituitary
      derived glycoprotein hormones. In an effort to identify the genetic mechanisms
      controlling the elevated plasma levels of pituitary-derived glycoprotein hormones
      [in particular, follicle-stimulating hormone (FSH)] and to determine whether some
      of these genetic factors are also responsible for differences in other
      phenotypes, we scanned the entire genome for regions that affected plasma FSH in
      boars from a Meishan-White Composite (equal contributions of Chester White,
      Landrace, Large White, and Yorkshire) resource population. Initially, the entire
      genome of 121 boars was scanned for regions that potentially influenced plasma
      FSH. The most significant genomic regions were further studied in a total of 436
      boars. Three genomic regions located on chromosomes 3, 10, and X apparently
      possess genes that significantly affect FSH level, and one region provided
      suggestive evidence for the presence of FSH-controlling genes located on
      chromosome 8. The region on the X chromosome also affected testes size. Similar
      genomic regions to those identified on chromosomes 3, 8, and 10 in this study
      have been identified to affect ovulation rate in female litter mates, supporting
      the hypothesis that plasma FSH in pubertal boars and ovulation rate in females is
      controlled by a similar set of genes.

PMID- 11526199
TI  - Skeletal muscle Na currents in mice heterozygous for Six5 deficiency.
AB  - Myotonic dystrophy results from a trinucleotide repeat expansion between the
      myotonic dystrophy protein kinase gene (Dmpk), which encodes a serine-threonine
      protein kinase, and the Six5 gene, which encodes a homeodomain protein. The
      disease is characterized by late bursts of skeletal muscle Na channel openings,
      and this is recapitulated in Dmpk -/- and Dmpk +/- murine skeletal muscle. To
      test whether deficiency of the nearby Six5 gene also affected Na channel gating
      in murine skeletal muscle, we measured Na currents from cell-attached patches in
      Six5 +/- mice and age-matched wild-type and Dmpk +/- mice. Late bursts of Na
      channel activity were defined as an opening probability >10% measured from 10 to
      110 ms after depolarization. There was no significant difference in the
      occurrence of late Na channel bursts in wild-type and Six5 +/- muscle, whereas in
      Dmpk +/- muscle there was greater than fivefold increase in late bursts (P <
      0.001). Compared with wild-type mice, Na current amplitude was unchanged in Six5
      +/- muscle, whereas in Dmpk +/- muscle it was 36% reduced (P < 0.05). Thus, since
      Six5 +/- mice do not exhibit the Na channel gating abnormality of Dmpk
      deficiency, we conclude that Six5 deficiency does not contribute to the Na
      channel gating abnormality seen in dystrophia myotonica patients.

PMID- 11526200
TI  - Oxygen-dependent expression of hypoxia-inducible factor-1alpha in renal medullary
      cells of rats.
AB  - Hypoxia-inducible factor-1alpha (HIF-1alpha) is a transcription factor that
      regulates the oxygen-dependent expression of a number of genes. This
      transcription factor may contribute to the abundant expression of many genes in
      renal medullary cells that function normally under hypoxic conditions. The
      present study was designed to determine the characteristics of HIF-1alpha cDNA
      cloned from the rat kidney and the expression profile of HIF-1alpha in different
      kidney regions and to explore the mechanism activating or regulating HIF-1alpha
      expression in renal medullary cells. A 3,718-bp HIF-1alpha cDNA from the rat
      kidney was first cloned and sequenced using RT-PCR and TA cloning technique. It
      was found that 823 amino acids deduced from this renal HIF-1alpha cDNA had 99%,
      96%, and 90% identity with rat, mouse, or human HIF-1alpha deposited in GenBank,
      respectively. The 3'-untranslated region of HIF-1alpha mRNA from the rat kidney
      contained seven AUUUA instability elements, five of which were found to be
      conserved among rat, mouse, and human HIF-1alpha. Northern blot analyses
      demonstrated a corticomedullary gradient of HIF-1alpha mRNA expression in the
      kidney, with the greatest abundance in the renal inner medulla. Western blot
      analyses also detected a higher HIF-1alpha protein level in the nuclear extracts
      from the renal medulla than the renal cortex. A classic loop diuretic, furosemide
      (10 mg/kg ip), markedly increased renal medullary Po(2) levels from 22.5 to 52.2
      mmHg, which was accompanied by a significant reduction of HIF-1alpha transcripts
      in renal medullary tissue. In in vitro experiments, low Po(2), but not elevated
      osmolarity, was found to significantly increase HIF-1alpha mRNA in renal
      medullary interstitial cells and inner medullary collecting duct cells. These
      results indicate that HIF-1alpha is more abundantly expressed in the renal
      medulla compared with the renal cortex. Increased abundance of HIF-1alpha mRNA in
      the renal medulla may represent an adaptive response of renal medullary cells to
      low Po(2).

PMID- 11526201
TI  - Gene expression following acute morphine administration.
AB  - The long-term response to neurotropic drugs depends on drug-induced
      neuroplasticity and underlying changes in gene expression. However, alterations
      in neuronal gene expression can be observed even following single injection. To
      investigate the extent of these changes, gene expression in the medial striatum
      and lumbar part of the spinal cord was monitored by cDNA microarray following
      single injection of morphine. Using robust and resistant linear regression (MM
      estimator) with simultaneous prediction confidence intervals, we detected
      differentially expressed genes. By combining the results with cluster analysis,
      we have found that a single morphine injection alters expression of two major
      groups of genes, for proteins involved in mitochondrial respiration and for
      cytoskeleton-related proteins. RNAs for these proteins were mostly downregulated
      both in the medial striatum and in lumbar part of the spinal cord. These
      transitory changes were prevented by coadministration of the opioid antagonist
      naloxone. Data indicate that microarray analysis by itself is useful in
      describing the effect of well-known substances on the nervous system and provides
      sufficient information to propose a potentially novel pathway mediating its
      activity.

PMID- 11526202
TI  - Identification of two susceptibility loci for vascular fragility in the Brown
      Norway rat.
AB  - A trait of vascular fragility, characterized by the formation of abrupt defects
      within the elastic laminae of the abdominal aorta, has been identified in Brown
      Norway (BN) rats. These lesions are greatly exacerbated in F(1) rats from a BN x
      New Zealand genetically hypertensive (GH) intercross, implying that the genetic
      background provided by the GH rat influences lesion severity. The F(2) progeny of
      the BN x GH intercross were used to identify susceptibility loci for the lesions
      as well as exacerbating loci. Two major quantitative trait loci (QTLs) for number
      of internal elastic lamina lesions were identified on rat chromosomes 5 and 10,
      with the maximum "log of the odds ratio" (LOD) scores at D5Rat119 (LOD 5.0) and
      at D10Mit2 (LOD 4.5), respectively, together contributing 33.5% to the genetic
      variance. Further analysis revealed that the chromosome 10 locus exhibits a
      dominant mode of inheritance, with BN alleles being associated with increased
      lesion number (P < 0.0002) compared with GH homozygotes. This locus was in
      epistasis to a modifier locus on rat chromosome 2 at D2Mit14 (LOD score 2.12). A
      second major locus was identified on chromosome 5, exhibiting a semidominant mode
      of inheritance, again with the BN allele being significantly associated with
      increased lesion number (P < 0.0001). Furthermore, a locus influencing lesion
      severity was identified on chromosome 3 wherein GH alleles associated with
      increased severity. This is the first study to identify susceptibility loci for
      vascular elastic tissue fragility.

PMID- 11526203
TI  - Induction of CD4(+) T cell-dependent CD8(+) type 1 responses in humans by a
      malaria DNA vaccine.
AB  - We assessed immunogenicity of a malaria DNA vaccine administered by needle i.m.
      or needleless jet injection [i.m. or i.m./intradermally (i.d.)] in 14 volunteers.
      Antigen-specific IFN-gamma responses were detected by enzyme-linked immunospot
      (ELISPOT) assays in all subjects to multiple 9- to 23-aa peptides containing
      class I and/or class II restricted epitopes, and were dependent on both CD8(+)
      and CD4(+) T cells. Overall, frequency of response was significantly greater
      after i.m. jet injection. CD8(+)-dependent cytotoxic T lymphocytes (CTL) were
      detected in 8/14 volunteers. Demonstration in humans of elicitation of the class
      I restricted IFN-gamma responses we believe necessary for protection against the
      liver stage of malaria parasites brings us closer to an effective malaria
      vaccine.

PMID- 11526204
TI  - Receptor-like kinases from Arabidopsis form a monophyletic gene family related to
      animal receptor kinases.
AB  - Plant receptor-like kinases (RLKs) are proteins with a predicted signal sequence,
      single transmembrane region, and cytoplasmic kinase domain. Receptor-like kinases
      belong to a large gene family with at least 610 members that represent nearly
      2.5% of Arabidopsis protein coding genes. We have categorized members of this
      family into subfamilies based on both the identity of the extracellular domains
      and the phylogenetic relationships between the kinase domains of subfamily
      members. Surprisingly, this structurally defined group of genes is monophyletic
      with respect to kinase domains when compared with the other eukaryotic kinase
      families. In an extended analysis, animal receptor kinases, Raf kinases, plant
      RLKs, and animal receptor tyrosine kinases form a well supported group sharing a
      common origin within the superfamily of serine/threonine/tyrosine kinases. Among
      animal kinase sequences, Drosophila Pelle and related cytoplasmic kinases fall
      within the plant RLK clade, which we now define as the RLK/Pelle family. A survey
      of expressed sequence tag records for land plants reveals that mosses, ferns,
      conifers, and flowering plants have similar percentages of expressed sequence
      tags representing RLK/Pelle homologs, suggesting that the size of this gene
      family may have been close to the present-day level before the diversification of
      land plant lineages. The distribution pattern of four RLK subfamilies on
      Arabidopsis chromosomes indicates that the expansion of this gene family is
      partly a consequence of duplication and reshuffling of the Arabidopsis genome and
      of the generation of tandem repeats.

PMID- 11526205
TI  - Oligodendrocyte lineage genes (OLIG) as molecular markers for human glial brain
      tumors.
AB  - The most common primary tumors of the human brain are thought to be of glial cell
      origin. However, glial cell neoplasms cannot be fully classified by cellular
      morphology or with conventional markers for astrocytes, oligodendrocytes, or
      their progenitors. Recent insights into central nervous system tumorigenesis
      suggest that novel molecular markers might be found among factors that have roles
      in glial development. Oligodendrocyte lineage genes (Olig1/2) encode basic helix
      loop-helix transcription factors. In the rodent central nervous system, they are
      expressed exclusively in oligodendrocytes and oligodendrocyte progenitors, and
      Olig1 can promote formation of an chondroitin sulfate proteoglycon-positive glial
      progenitor. Here we show that human OLIG genes are expressed strongly in
      oligodendroglioma, contrasting absent or low expression in astrocytoma. Our data
      provide evidence that neoplastic cells of oligodendroglioma resemble
      oligodendrocytes or their progenitor cells and may derive from cells of this
      lineage. They further suggest the diagnostic potential of OLIG markers to augment
      identification of oligodendroglial tumors.

PMID- 11526206
TI  - In vivo mechanism-based inactivation of S-adenosylmethionine decarboxylases from
      Escherichia coli, Salmonella typhimurium, and Saccharomyces cerevisiae.
AB  - S-adenosylmethionine decarboxylase (AdoMetDC), a key enzyme in the biosynthesis
      of spermidine and spermine, is first synthesized as a proenzyme, which is cleaved
      posttranslationally to form alpha and beta subunits. The alpha subunit contains a
      covalently bound pyruvoyl group derived from serine that is essential for
      activity. With the use of an Escherichia coli overexpression system, we have
      purified AdoMetDCs encoded by the E. coli, Saccharomyces cerevisiae, and
      Salmonella typhimurium genes. Unexpectedly we found by mass spectrometry that
      these enzymes had been modified posttranslationally in vivo by a mechanism-based
      "suicide" inactivation. A large percentage of the alpha subunit of each enzyme
      had been modified in vivo to give peaks with masses m/z = 57 +/- 1 and m/z = 75
      +/- 1 daltons higher than the parent peak. AdoMetDC activity decreased markedly
      during overexpression concurrently with the increase of the additional peaks for
      the alpha subunit. Sequencing of a tryptic fragment by tandem mass spectrometry
      showed that Cys-140 was modified with a +75 +/- 1 adduct, which is probably
      derived from the reaction product. Comparable modification of the alpha subunit
      was also observed in in vitro experiments after incubation with the substrate or
      with the reaction product, which is consistent with the in vitro alkylation of E.
      coli AdoMetDC reported by Diaz and Anton [Diaz, E. & Anton, D. L. (1991)
      Biochemistry 30, 4078-4081].

PMID- 11526207
TI  - The plug domain of FepA, a TonB-dependent transport protein from Escherichia
      coli, binds its siderophore in the absence of the transmembrane barrel domain.
AB  - FepA, an outer membrane iron siderophore transporter from Escherichia coli, is
      composed of a 22-stranded membrane-spanning beta barrel with a globular N
      terminal "plug" domain of 148 residues that folds up inside the barrel and
      completely occludes the barrel's interior (1). We have overexpressed and purified
      this plug domain by itself and find that it behaves in vitro as a predominantly
      unfolded yet soluble protein, as determined by circular dichroism, thermal
      denaturation, and NMR studies. Despite its unfolded state, the isolated domain
      binds ferric enterobactin, the siderophore ligand of FepA, with an affinity of 5
      microM, just 100-fold reduced from that of intact FepA. These findings argue
      against the hypothesis that the plug domain is pulled intact from the barrel
      during transport in vivo but may be consistent either with a model where the plug
      rearranges within the barrel to create a channel large enough to allow transport
      or with a model where the plug unfolds and comes out of the barrel.

PMID- 11526208
TI  - Conversion of monomeric protein L to an obligate dimer by computational protein
      design.
AB  - Protein L consists of a single alpha-helix packed on a four-stranded beta-sheet
      formed by two symmetrically opposed beta-hairpins. We use a computer-based
      protein design procedure to stabilize a domain-swapped dimer of protein L in
      which the second beta-turn straightens and the C-terminal strand inserts into the
      beta-sheet of the partner. The designed obligate dimer contains three mutations
      (A52V, N53P, and G55A) and has a dissociation constant of approximately 700 pM,
      which is comparable to the dissociation constant of many naturally occurring
      protein dimers. The structure of the dimer has been determined by x-ray
      crystallography and is close to the in silico model.

PMID- 11526209
TI  - Adult-generated hippocampal and neocortical neurons in macaques have a transient
      existence.
AB  - Previously we reported that new neurons are added to the hippocampus and
      neocortex of adult macaque monkeys. Here we compare the production and survival
      of adult-generated neurons and glia in the dentate gyrus, prefrontal cortex, and
      inferior temporal cortex. Twelve adult macaques were injected with the thymidine
      analogue BrdUrd, and the phenotypes of labeled cells were examined after 2 h, 24
      h, 2 wk, 5 wk, 9 wk, and 12 wk by using the following immunocytochemical markers:
      for immature and mature neurons, class III beta-tubulin (TuJ1); for mature
      neurons, neuronal nuclei; for astrocytes, glial fibrillary acidic protein; and
      for oligodendrocytes, 2',3'-cyclic nucleotide 3' phosphodiesterase. We found that
      the dentate gyrus had many more BrdUrd-labeled cells than either neocortical
      area. Furthermore, a greater percentage of BrdUrd-labeled cells expressed a
      neuronal marker in the dentate gyrus than in either neocortical area. The number
      of new cells in all three areas declined by 9 wk after BrdUrd labeling,
      suggesting that some of the new cells have a transient existence. BrdUrd-labeled
      cells also were found in the subventricular zone and in the white matter between
      the lateral ventricle and neocortex; some of the latter cells were double-labeled
      for BrdUrd and TuJ1. Adult neocortical neurogenesis is not restricted to
      primates. Five adult rats were injected with BrdUrd, and after a 3-wk survival
      time, there were cells double-labeled for BrdUrd and either TuJ1 or neuronal
      nuclei in the anterior neocortex as well as the dentate gyrus.

PMID- 11526210
TI  - Multiwavelength anomalous diffraction analysis at the M absorption edges of
      uranium.
AB  - The multiwavelength anomalous diffraction (MAD) method for phase evaluation is
      now widely used in macromolecular crystallography. Successful MAD structure
      determinations have been carried out at the K or L absorption edges of a variety
      of elements. In this study, we investigate the anomalous scattering properties of
      uranium at its M(IV) (3.326 A) and M(V) (3.490 A) edge. Fluorescence spectra
      showed remarkably strong anomalous scattering at these edges (f' = -70e, f" = 80e
      at the M(IV) edge and f' = -90e, f" = 105e at the M(V) edge), many times higher
      than from any anomalous scatterers used previously for MAD phasing. However, the
      large scattering angles and high absorption at the low energies of these edges
      present some difficulties not found in typical crystallographic studies. We
      conducted test experiments at the M(IV) edge with crystals of porcine elastase
      derivatized with uranyl nitrate. A four-wavelength MAD data set complete to 3.2-A
      Bragg spacings was collected from a single small frozen crystal. Analysis of the
      data yielded satisfactory phase information (average difference of (0)phi(T) -
      (0)phi(A) for replicated determinations is 32 degrees ) and produced an
      interpretable electron-density map. Our results demonstrate that it is practical
      to measure macromolecular diffraction data at these edges with current
      instrumentation and that phase information of good accuracy can be extracted from
      such experiments. We show that such experiments have potential for the phasing of
      very large macromolecular assemblages.

PMID- 11526211
TI  - Prediction of cognitive decline in normal elderly subjects with 2-[(18)F]fluoro-2
      deoxy-D-glucose/poitron-emission tomography (FDG/PET).
AB  - Neuropathology studies show that patients with mild cognitive impairment (MCI)
      and Alzheimer's disease typically have lesions of the entorhinal cortex (EC),
      hippocampus (Hip), and temporal neocortex. Related observations with in vivo
      imaging have enabled the prediction of dementia from MCI. Although individuals
      with normal cognition may have focal EC lesions, this anatomy has not been
      studied as a predictor of cognitive decline and brain change. The objective of
      this MRI-guided 2-[(18)F]fluoro-2-deoxy-d-glucose/positron-emission tomography
      (FDG/PET) study was to examine the hypothesis that among normal elderly subjects,
      EC METglu reductions predict decline and the involvement of the Hip and
      neocortex. In a 3-year longitudinal study of 48 healthy normal elderly, 12
      individuals (mean age 72) demonstrated cognitive decline (11 to MCI and 1 to
      Alzheimer's disease). Nondeclining controls were matched on apolipoprotein E
      genotype, age, education, and gender. At baseline, metabolic reductions in the EC
      accurately predicted the conversion from normal to MCI. Among those who declined,
      the baseline EC predicted longitudinal memory and temporal neocortex metabolic
      reductions. At follow-up, those who declined showed memory impairment and
      hypometabolism in temporal lobe neocortex and Hip. Among those subjects who
      declined, apolipoprotein E E4 carriers showed marked longitudinal temporal
      neocortex reductions. In summary, these data suggest that an EC stage of brain
      involvement can be detected in normal elderly that predicts future cognitive and
      brain metabolism reductions. Progressive E4-related hypometabolism may underlie
      the known increased susceptibility for dementia. Further study is required to
      estimate individual risks and to determine the physiologic basis for METglu
      changes detected while cognition is normal.

PMID- 11526212
TI  - Localized cerebral blood flow response at submillimeter columnar resolution.
AB  - Functional magnetic resonance imaging (fMRI) has been widely used for imaging
      brain functions. However, the extent of the fMRI hemodynamic response around the
      active sites, at submillimeter resolution, remains poorly understood and
      controversial. With the use of perfusion-based fMRI, we evaluated the hemodynamic
      response in the cat visual cortex after orientation-specific stimuli. Activation
      maps obtained by using cerebral blood flow fMRI measurements were predominantly
      devoid of large draining vein contamination and reproducible at columnar
      resolution. Stimulus-specific cerebral blood flow responses were spatially
      localized to individual cortical columns, and columnar layouts were resolved. The
      periodic spacing of orientation columnar structures was estimated to be 1.1 +/-
      0.2 mm (n = 14 orientations, five animals), consistent with previous findings.
      The estimated cerebral blood flow response at full width at half-maximum was 470
      microm under single-stimulus conditions without differential subtraction. These
      results suggest that hemodynamic-based fMRI can indeed be used to map individual
      functional columns if large-vessel contributions can be minimized or eliminated.

PMID- 11526213
TI  - A model for melanosome biogenesis based on the purification and analysis of early
      melanosomes.
AB  - Melanosome biogenesis and function were studied after purification of early stage
      melanosomes and characterization of specific proteins sorted to that organelle.
      Melanosomes were isolated from highly pigmented human MNT1 melanoma cells after
      disruption and initial separation by sucrose density gradient centrifugation. Low
      density sucrose fractions were found by electron microscopy to be enriched in
      stage I and stage II melanosomes, and these fractions were further separated and
      purified by free flow electrophoresis. Tyrosinase and dopachrome tautomerase
      (DCT) activities were found exclusively in stage II melanosomes, even though DCT
      (and to some extent tyrosinase) proteins were sorted to stage I melanosomes.
      Western immunoblotting revealed that these catalytic proteins, as well as TYRP1,
      MART1, and GP100, were cleaved and inactivated in stage I melanosomes.
      Proteolytic cleavage was critical for the refolding of GP100 within the
      melanosomal milieu, and subsequent reorganization of amorphous stage I
      melanosomes into fibrillar, ovoid, and highly organized stage II melanosomes
      appears to stabilize the catalytic functions of melanosomal enzymes and allows
      melanin biosynthesis to begin. These results provide a better understanding of
      the structural features seen during melanosome biogenesis, and they yield further
      clues as to the physiological regulation of pigmentation.

PMID- 11526214
TI  - Multiple conformations of PEVK proteins detected by single-molecule techniques.
AB  - An important component of muscle elasticity is the PEVK region of titin, so named
      because of the preponderance of these amino acids. However, the PEVK region,
      similar to other elastomeric proteins, is thought to form a random coil and
      therefore its structure cannot be determined by standard techniques. Here we
      combine single-molecule electron microscopy and atomic force microscopy to
      examine the conformations of the human cardiac titin PEVK region. In contrast to
      a simple random coil, we have found that cardiac PEVK shows a wide range of
      elastic conformations with end-to-end distances ranging from 9 to 24 nm and
      persistence lengths from 0.4 to 2.5 nm. Individual PEVK molecules retained their
      distinctive elastic conformations through many stretch-relaxation cycles,
      consistent with the view that these PEVK conformers cannot be interconverted by
      force. The multiple elastic conformations of cardiac PEVK may result from varying
      degrees of proline isomerization. The single-molecule techniques demonstrated
      here may help elucidate the conformation of other proteins that lack a well
      defined structure.

PMID- 11526215
TI  - Nitric oxide-induced apoptosis in pancreatic beta cells is mediated by the
      endoplasmic reticulum stress pathway.
AB  - Excessive nitric oxide (NO) production in cytokine-activated beta cells has been
      implicated in beta cell disruption in type 1 diabetes. beta cells are very
      vulnerable to NO-induced apoptosis. However, the mechanism underlying this
      phenomenon is unclear. Low concentrations of NO that lead to apoptosis apparently
      do not cause severe DNA damage in mouse MIN6 beta cells. CHOP, a C/EBP homologous
      protein that is induced by endoplasmic reticulum (ER) stress and plays a role in
      growth arrest and cell death, was induced by a NO donor, S-nitroso-N-acetyl-D,L
      penicillamine (SNAP). SNAP increased cytosolic Ca(2+), and only agents depleting
      ER Ca(2+) induced CHOP expression and led to apoptosis, suggesting that NO
      depletes ER Ca(2+). Overexpression of calreticulin increased the Ca(2+) content
      of ER and afforded protection to cells against NO-mediated apoptosis.
      Furthermore, pancreatic islets from CHOP knockout mice showed resistance to NO.
      We conclude that NO depletes ER Ca(2+), causes ER stress, and leads to apoptosis.
      Thus, ER Ca(2+) stores are a new target of NO, and the ER stress pathway is a
      major mechanism of NO-mediated beta cell apoptosis.

PMID- 11526216
TI  - A role for IL-1 alpha in inducing pathologic inflammation during bacterial
      infection.
AB  - Infection with pathogenic microbes often results in a significant inflammatory
      response. A cascade of proinflammatory cytokines including tumor necrosis factor
      alpha (TNF-alpha) and IL-1 initiates this response. Although there is a clear
      role for IL-1 during infection, little is known to distinguish the role of IL-1
      alpha from that of IL-1 beta during this process. With the use of Yersinia
      enterocolitica as a model enteric pathogen, we have identified a specific role
      for IL-1 alpha in inducing pathologic inflammation during bacterial infection.
      Depletion of IL-1 alpha in mice infected with wild-type Y. enterocolitica results
      in significantly decreased intestinal inflammation. Furthermore, a bacterial
      mutant that does not induce IL-1 alpha expression but induces normal levels of IL
      1 beta, TNF-alpha, and IFN-gamma, causes greatly reduced intestinal inflammation
      and is attenuated by LD(50) analysis in the C57BL/6 mouse model. These results
      demonstrate a distinct and unrecognized role for IL-1 alpha in inducing
      intestinal inflammation that cannot be compensated for by the endogenous levels
      of IL-1 beta, TNF-alpha, or IFN-gamma that are produced in response to Y.
      enterocolitica. Additionally, these results suggest that IL-1 alpha-induced
      inflammation is a major contributor to the pathology of yersiniosis.

PMID- 11526217
TI  - Modulation of HIV-like particle assembly in vitro by inositol phosphates.
AB  - HIV-1 Gag protein assembles into 100- to 120-nm diameter particles in mammalian
      cells. Recombinant HIV-1 Gag protein assembles in a fully defined system in vitro
      into particles that are only 25-30 nm in diameter and that differ significantly
      in other respects from authentic particles. However, particles with the size and
      other properties of authentic virions were obtained in vitro by addition of
      inositol phosphates or phosphatidylinsitol phosphates to the assembly system.
      Thus, the interactions between HIV-1 Gag protein molecules are altered by binding
      of inositol derivatives; this binding is apparently essential for normal HIV-1
      particle assembly. This requirement is not seen in a deleted Gag protein lacking
      residues 16-99 within the matrix domain.

PMID- 11526218
TI  - Incomplete taxon sampling is not a problem for phylogenetic inference.
AB  - A major issue in all data collection for molecular phylogenetics is taxon
      sampling, which refers to the use of data from only a small representative set of
      species for inferring higher-level evolutionary history. Insufficient taxon
      sampling is often cited as a significant source of error in phylogenetic studies,
      and consequently, acquisition of large data sets is advocated. To test this
      assertion, we have conducted computer simulation studies by using natural
      collections of evolutionary parameters--rates of evolution, species sampling, and
      gene lengths--determined from data available in genomic databases. A comparison
      of the true tree with trees constructed by using taxa subsamples and trees
      constructed by using all taxa shows that the amount of phylogenetic error per
      internal branch is similar; a result that holds true for the neighbor-joining,
      minimum evolution, maximum parsimony, and maximum likelihood methods.
      Furthermore, our results show that even though trees inferred by using
      progressively larger taxa subsamples of a real data set become increasingly
      similar to trees inferred by using the full sample, all inferred trees are
      equidistant from the true tree in terms of phylogenetic error per internal
      branch. Our results suggest that longer sequences, rather than extensive
      sampling, will better improve the accuracy of phylogenetic inference.

PMID- 11526219
TI  - Human mitochondrial topoisomerase I.
AB  - Tension generated in the circular mitochondrial genome during replication and
      transcription points to the need for mtDNA topoisomerase activity. Here we report
      a 601-aa polypeptide highly homologous to nuclear topoisomerase I. The N-terminal
      domain of this novel topoisomerase contains a mitochondrial localization sequence
      and lacks a nuclear localization signal. Therefore, we refer to this polypeptide
      as top1mt. The pattern of top1mt expression matches the requirement for high
      mitochondrial activity in specific tissues. top1mt is a type IB topoisomerase
      that requires divalent metal (Ca(2+) or Mg(2+)) and alkaline pH for optimum
      activity. The TOP1mt gene is highly homologous to the nuclear TOP1 gene and
      consists of 14 exons. It is localized on human chromosome 8q24.3.

PMID- 11526221
TI  - Solvent interactions determine carbohydrate conformation.
AB  - The relationship between the three-dimensional structures of oligosaccharides and
      polysaccharides and their biological properties has been the focus of many recent
      studies. The overall conformation of an oligosaccharide depends primarily on the
      orientation of the torsion angles (phi, psi, and omega) between glycosyl
      residues. Numerous experimental studies have shown that in glucopyranosides the
      omega-torsion angle (O(6)-C(6)-C(5)-O(5)) displays a preference for gauche
      orientations, in disagreement with predictions based on gas-phase quantum
      mechanics calculations. In contrast, the omega-angle in galactopyranosides
      displays a high proportion of the anti-orientation. For oligosaccharides
      containing glycosidic linkages at the 6-position (1-->6 linked), variations in
      rotamer population have a direct effect on the oligosaccharides' structure and
      function, and yet the physical origin of these conformational preferences remains
      unclear. Although it is generally recognized that the gauche effect in
      carbohydrates is a solvent-dependent phenomenon, the mechanism through which
      solvent induces the gauche preference is not understood. In the present work,
      quantum mechanics and solvated molecular dynamics calculations were performed on
      two representative carbohydrates, methyl alpha-D-glucopyranoside and methyl alpha
      D-galactopyranoside. We show that correct reproduction of the experimental
      rotamer distributions about the omega-angles is obtained only after explicit
      water is included in the molecular dynamics simulations. The primary role of the
      water appears to be to disrupt the hydrogen bonding within the carbohydrate,
      thereby allowing the rotamer populations to be determined by internal electronic
      and steric repulsions between the oxygen atoms. The results reported here provide
      a quantitative explanation of the conformational behavior of (1-->6)-linked
      carbohydrates.

PMID- 11526220
TI  - Lateral transfer at the gene and subgenic levels in the evolution of eukaryotic
      enolase.
AB  - Enolase genes from land plants and apicomplexa (intracellular parasites,
      including the malarial parasite, Plasmodium) share two short insertions. This
      observation has led to the suggestion that the apicomplexan enolase is the
      product of a lateral transfer event involving the algal endosymbiont from which
      the apicomplexan plastid is derived. We have examined enolases from a wide
      variety of algae, as well as ciliates (close relatives of apicomplexa), to
      determine whether lateral transfer can account for the origin of the apicomplexan
      enolase. We find that lateral gene transfer, likely occurring intracellularly
      between endosymbiont and host nucleus, does account for the evolution of
      cryptomonad and chlorarachniophyte algal enolases but fails to explain the
      apicomplexan enolase. This failure is because the phylogenetic distribution of
      the insertions--which we find in apicomplexa, ciliates, land plants, and
      charophyte green algae--directly conflicts with the phylogeny of the gene itself.
      Protein insertions have traditionally been treated as reliable markers of
      evolutionary events; however, these enolase insertions do not seem to reflect
      accurately the evolutionary history of the molecule. The lack of congruence
      between insertions and phylogeny could be because of the parallel loss of both
      insertions in two or more lineages, or what is more likely, because the
      insertions were transmitted between distantly related genes by lateral transfer
      and fine-scale recombination, resulting in a mosaic gene. This latter process
      would be difficult to detect without such insertions to act as markers, and such
      mosaic genes could blur the "tree of life" beyond the extent to which whole-gene
      lateral transfer is already known to confound evolutionary reconstruction.

PMID- 11526223
TI  - Two by two: the pairings of P-selectin and P-selectin glycoprotein ligand 1.

PMID- 11526222
TI  - CD40 stimulation accelerates deletion of tumor-specific CD8(+) T cells in the
      absence of tumor-antigen vaccination.
AB  - Previous work has established a role for CD40-mediated signals in eliciting
      helper-dependent CD8(+) T cell responses. Here we investigated the effects of in
      vivo CD40 stimulation on the survival and function of tumor-specific CD8(+) T
      cells in a mouse melanoma model system. We found that agonistic anti-CD40
      antibody treatment alone of tumor-bearing mice accelerated the deletion of tumor
      antigen-specific T cells. However, long-term survival and function of tumor
      antigen-specific T cells could be achieved when viral immunization with tumor
      antigen and anti-CD40 treatment were combined. This rescue of CD8(+) T cells
      could not be easily replicated by inflammatory or antigen-specific stimuli alone,
      demonstrating the specificity of signals that regulate the deletion or survival
      of tumor-specific T cells. These results demonstrate that opposing effects can be
      elicited by CD40 stimulation in vivo and suggest the need for caution in using
      this treatment for cancer patients.

PMID- 11526224
TI  - Making sense (and antisense) of the X inactivation center.

PMID- 11526225
TI  - Targeted therapies for killing tumor cells.

PMID- 11526227
TI  - C(m)C(a/t)GG methylation: a new epigenetic mark in mammalian DNA?

PMID- 11526226
TI  - Linking molecular therapeutics to molecular diagnostics: inhibition of the
      FRAP/RAFT/TOR component of the PI3K pathway preferentially blocks PTEN mutant
      cells in vitro and in vivo.

PMID- 11526228
TI  - Chiral exciton coupling of merocyanine dyes within a well defined hydrogen-bonded
      assembly.
AB  - Multichromophoric hydrogen-bonded assemblies 1(3) small middle dot(BAR)(6) are
      studied that bear a remarkably close resemblance to commelinin, a naturally
      occurring assembly responsible for an intense blue color of flowers. The
      incorporated chromophores exhibit a hypsochromic shift in the UV/visible (Vis)
      absorption maximum (Delta lambda(max) = 14 nm) compared with the free
      chromophores. In addition, the chiroptical properties of incorporated
      chromophores can be rationally controlled by changing the supramolecular
      chirality of the assembly. These properties have been used to study the stability
      of this type of assembly with UV and CD spectroscopy at concentrations far below
      the NMR sensitivity threshold (10(-4) M). The determined C(50%) values of 2-3
      microM in benzene show the extremely high stability of these hydrogen-bonded
      assemblies.

PMID- 11526229
TI  - The see-through medaka: a fish model that is transparent throughout life.
AB  - The see-through medaka is a vertebrate model with a transparent body in the adult
      stage, as well as during the embryonic stages, that was generated from a small
      laboratory fish, medaka (Oryzias latipes). In this fish model, most of the
      pigments are genetically removed from the entire body by a combination of
      recessive alleles at four loci. The main internal organs, namely, heart, spleen,
      blood vessels, liver, gut, gonads, kidney, brain, spinal cord, lens, air bladder,
      and gills, in living adult fish are visible to the naked eye or with a simple
      stereoscopic microscope. This fish is healthy and fertile. A transgenic see
      through medaka was produced by using the green fluorescent protein (GFP) gene
      fused to the regulatory regions of the medaka vasa gene, in which germ cell
      specific expression of GFP was visualized. The fluorescent tag also efficiently
      improved visibility of gonadal tissues. The process of oocyte maturation in the
      ovary was monitored by repeated observations from the outside of the body during
      one spawning cycle in the same living females of the transgenic see-through
      stock. The see-through medaka will provide an opportunity for noninvasive studies
      of morphological and molecular events that occur in internal organs in the later
      stages of life.

PMID- 11526231
TI  - Phospholamban domain IB forms an interaction site with the loop between
      transmembrane helices M6 and M7 of sarco(endo)plasmic reticulum Ca2+ ATPases.
AB  - Transmembrane helix M6 of the sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA)
      has been shown to form a site of interaction with phospholamban (PLN). Site
      directed mutagenesis was carried out in the cytoplasmic loop (L67) between M6 and
      M7 in SERCA1a to detect other SERCA-PLN binding sites. Mutants N810A, D813A, and
      R822A had diminished ability to interact functionally with PLN, but only D813A
      and R822A had reduced physical interaction with PLN. PLN mutants R25A, Q26A,
      N27A, L28A, Q29A, and N30A had enhanced physical interaction with wild-type (wt)
      SERCA1a, but physical interaction of these PLN mutants with SERCA1a mutants D813A
      and R822A was reduced about 2.5 fold (range 1.44-2.82). Exceptions were the
      interactions of PLN N27A and N30A with SERCA1a D813A, which were reduced by 7.3-
      and 5.8-fold, respectively. A superinhibitory PLN deletion mutant, PLNDelta21-29,
      had strong physical interactions with SERCA1a and with SERCA1a mutant D813A.
      Physical interactions with SERCA1a and mutant D813A were sharply diminished,
      however, for the PLN deletion mutant, PLNDelta21-30, lacking PLN N30. Physical
      interactions between SERCA1a and a PLN-cytochrome b(5) chimera containing PLN
      residues 1-29 were much stronger than those between a PLN-cytochrome b(5) chimera
      containing PLN residues 1-21 and lacking N27. These results suggest that a SERCA1
      PLN interaction site occurs between L67 of SERCA1a and domain IB of PLN, which
      involves SERCA1a D813 and PLN N27 and N30.

PMID- 11526230
TI  - Symmetrical dimer of the human dopamine transporter revealed by cross-linking Cys
      306 at the extracellular end of the sixth transmembrane segment.
AB  - There is evidence both for and against Na(+)- and Cl(-)-dependent
      neurotransmitter transporters forming oligomers. We found that cross-linking the
      human dopamine transporter (DAT), which is heterologously expressed in human
      embryonic kidney 293 cells, either with copper phenanthroline (CuP) or the
      bifunctional reagent bis-(2-methanethiosulfonatoethyl)amine hydrochloride (bis
      EA) increased the apparent molecular mass determined with nonreducing SDS/PAGE
      from approximately 85 to approximately 195 kDa. After cross-linking, but not
      before, coexpressed, differentially epitope-tagged DAT molecules, solubilized in
      Triton X-100, were coimmunoprecipitated. Thus, the 195-kDa complex was a
      homodimer. Cross-linking of DAT did not affect tyramine uptake. Replacement of
      Cys-306 with Ala prevented cross-linking. Replacement of all of the non-disulfide
      bonded cysteines in the extracellular and membrane domains, except for Cys-306,
      did not prevent cross-linking. We conclude that the cross-link is between Cys-306
      at the extracellular end of TM6 in each of the two DATs. The motif GVXXGVXXA
      occurs at the intracellular end of TM6 in DAT and is found in a number of other
      neurotransmitter transporters. This sequence was originally found at the
      dimerization interface in glycophorin A, and it promotes dimerization in model
      systems. Mutation of either glycine disrupted DAT expression and function. The
      intracellular end of TM6, like the extracellular end, is likely to be part of the
      dimerization interface.

PMID- 11526232
TI  - Why multiple small subunits (Y2 and Y4) for yeast ribonucleotide reductase?
      Toward understanding the role of Y4.
AB  - Ribonucleotide reductases (RNRs) catalyze the conversion of nucleotides to
      deoxynucleotides. Class I RNRs are composed of two homodimeric subunits: R1 and
      R2. R1 is directly involved in the reduction, and R2 contains the diferric
      tyrosyl radical (Y*) cofactor essential for the initiation of reduction.
      Saccharomyces cerevisiae has two RNRs; Y1 and Y3 correspond to R1, whereas Y2 and
      Y4 correspond to R2. Y4 is essential for diferric-Y* formation in Y2 from apoY2,
      Fe(2+), and O(2). The actual function of Y4 is controversial. Y2 and Y4 have been
      further characterized in an effort to understand their respective roles in
      nucleotide reduction. (His)(6)-Y2, Y4, and (His)(6)-Y4 are homodimers, isolated
      largely in apo form. Their CD spectra reveal that they are predominantly helical.
      The concentrations of Y2 and Y4 in vivo are 0.5-2.3 microM, as determined by
      Western analysis. Incubation of Y2 and Y4 under physiological conditions
      generates apo Y2Y4 heterodimer, which can form a diferric-Y small middle dot when
      incubated with Fe(2+) and O(2). Holo Y2Y4 heterodimer contains 0.6-0.8 Y* and has
      a specific activity of 0.8-1.3 micromol.min.mg. Titration of Y2 with Y4 in the
      presence of Fe(2+) and O(2) gives maximal activity with one equivalent of Y4 per
      Y2. Models for the function of Y4 based on these data and the accompanying
      structure will be discussed.

PMID- 11526233
TI  - Structure of the yeast ribonucleotide reductase Y2Y4 heterodimer.
AB  - The R2 subunits of class I ribonucleotide reductases (RNRs) house a diferric
      tyrosyl radical (Y*) cofactor essential for DNA synthesis. In yeast, there are
      two R2 proteins, Y2 and Y4. Although both Y2 and Y4 are homologous to R2s from
      other organisms, Y4 lacks three conserved iron-binding residues, and its exact
      function is unclear. Y4 is required for assembly of the diferric-Y* cofactor in
      Y2, and the two proteins can form both homodimeric and heterodimeric complexes.
      The Y2Y4 heterodimer was crystallized from a mixture of the two proteins, and its
      structure was determined to 2.8 A resolution. Both Y2 and Y4 are completely alpha
      helical and resemble the mouse and Escherichia coli R2s in overall fold. Three
      alpha helices not observed in the mouse R2 structure are present at the Y2 N
      terminus, and one extra N-terminal helix is observed in Y4. In addition, one of
      the eight principal helices in both Y2 and Y4, alphaD, is shifted significantly
      from its position in mouse R2. The heterodimer interface is similar to the mouse
      R2 homodimer interface in size and interacting residues, but loop regions at the
      interface edges differ. A single metal ion, assigned as Zn(II), occupies the Fe2
      position in the Y2 active site. Treatment of the crystals with Fe(II) results in
      difference electron density consistent with formation of a diiron center. No
      metal-binding site is observed in Y4. Instead, the residues in the active site
      region form a hydrogen-bonding network involving an arginine, two glutamic acids,
      and a water molecule.

PMID- 11526234
TI  - A hemoglobin from plants homologous to truncated hemoglobins of microorganisms.
AB  - We have identified a nuclear-encoded Hb from plants (GLB3) that has a central
      domain similar to the "truncated" Hbs of bacteria, protozoa, and algae. The three
      dimensional structure of these Hbs is a 2-on-2 arrangement of alpha-helices,
      distinct from the 3-on-3 arrangement of the standard globin fold [Pesce, A.,
      Couture, M., Dewilde, S., Guertin, M., Yamauchi, K., Ascenzi, P., Moens, L. &
      Bolognesi, M. (2000) EMBO J. 19, 2424-2434]. GLB3-like genes are not found in
      animals or yeast, but our analysis reveals that they are present in a wide range
      of Angiosperms and a Bryophyte. Although cyanobacteria and Chlamydomonas have 2
      on-2 Hbs (GLBN), GLB3 is more likely related to GLBO-type 2-on-2 Hbs from
      bacteria. Consequently, GLB3 is unlikely to have arisen from a horizontal
      transfer between the chloroplast and nuclear genomes. Arabidopsis thaliana GLB3
      protein exhibits unusual concentration-independent binding of O(2) and CO. The
      absorbance spectrum of deoxy-GLB3 is unique; the protein forms a transient six
      coordinate structure after reduction and deoxygenation, which slowly converts to
      a five-coordinate structure. In A. thaliana, GLB3 is expressed throughout the
      plant but responds to none of the treatments that induce plant 3-on-3 Hbs. Our
      analysis of the sequence, ligand interactions, and expression profile of GLB3
      indicates that this protein has unique biochemical properties, evolutionary
      history, and, most likely, a function distinct from those of other plant Hbs.

PMID- 11526235
TI  - Regulation of SR protein localization during development.
AB  - Ser-Arg-rich (SR) proteins play numerous roles in spliceosome assembly and the
      regulation of splice-site selection. Whereas considerable attention has focused
      on the mechanistic details of SR protein activities, little is known concerning
      how these splicing regulators are controlled by the cell. Here we examined the
      subcellular localization of precursor mRNA splicing factors during early
      development of the nematode Ascaris lumbricoides. In the early embryo, before
      major zygotic gene activation, most SR proteins, along with RNA polymerase II,
      are localized in the cytoplasm. As development proceeds, we observe a significant
      decrease in the cytoplasmic levels of these factors and a concomitant increase in
      nuclear localization. In contrast, trimethylguanosine-capped small nuclear
      ribonucleoproteins are predominantly localized in the nucleus throughout this
      period. We previously showed that the phosphorylation state and activity of SR
      proteins are regulated during A. lumbricoides embryogenesis. These changes
      correlate with the onset of precursor mRNA splicing and zygotic transcription.
      Thus, a coordinate change in the subcellular localization of SR proteins and RNA
      polymerase II occurs at the transition from reliance on maternally deposited
      factors to embryonic expression. We propose that before zygotic gene activation,
      SR proteins and RNA polymerase II are stockpiled in the cytoplasm of early
      embryos, awaiting signals that lead to their activation.

PMID- 11526236
TI  - The Eurasian heartland: a continental perspective on Y-chromosome diversity.
AB  - The nonrecombining portion of the human Y chromosome has proven to be a valuable
      tool for the study of population history. The maintenance of extended haplotypes
      characteristic of particular geographic regions, despite extensive admixture,
      allows complex demographic events to be deconstructed. In this study we report
      the frequencies of 23 Y-chromosome biallelic polymorphism haplotypes in 1,935 men
      from 49 Eurasian populations, with a particular focus on Central Asia. These
      haplotypes reveal traces of historical migrations, and provide an insight into
      the earliest patterns of settlement of anatomically modern humans on the Eurasian
      continent. Central Asia is revealed to be an important reservoir of genetic
      diversity, and the source of at least three major waves of migration leading into
      Europe, the Americas, and India. The genetic results are interpreted in the
      context of Eurasian linguistic patterns.

PMID- 11526237
TI  - Attributes of gammadelta intraepithelial lymphocytes as suggested by their
      transcriptional profile.
AB  - gammadelta T lymphocytes in the intestinal intraepithelial layer (gammadelta
      IELs) are thought to contribute to immune competence, but their actual function
      remains poorly understood. Here we used DNA microarrays to study the gene
      expression profile of gammadelta IELs in a Yersinia infection system to better
      define their roles. To validate this approach, mesenteric lymph node CD8(+)
      alphabeta T cells were similarly analyzed. The transcription profiles show that,
      whereas lymph node CD8(+) alphabeta T cells must be activated to become cytotoxic
      effectors, gammadelta IELs are constitutively activated and appear to use
      different signaling cascades. Our data suggest that gammadelta IELs may respond
      efficiently to a broad range of pathological situations irrespective of their
      diverse T cell antigen receptor repertoire. gammadelta IELs may modulate local
      immune responses and participate in intestinal lipid metabolism, cholesterol
      homeostasis, and physiology. This study provides a strong basis for further
      investigations of the roles of these cells as well as mucosal immune defense in
      general.

PMID- 11526238
TI  - Germinal center-associated nuclear protein (GANP) has a phosphorylation-dependent
      DNA-primase activity that is up-regulated in germinal center regions.
AB  - Antigen stimulation induces a rapid proliferation of B cells for expansion of
      specific B cell clones and their further differentiation into antibody-producing
      cells in germinal centers of T-dependent antigen-immunized mice. Previously, we
      identified a 210-kDa germinal center-associated nuclear protein (GANP) that is up
      regulated selectively in germinal centers and carries an MCM-binding domain in
      the carboxyl-terminal side. In addition, here, we found a region (from 414 to 550
      aa) in GANP molecule that is slightly similar to the known DNA-primase component
      p49. The recombinant GANP fragment covering this region synthesizes RNA primers
      for extension by DNA polymerase I with single-stranded DNA templates in vitro.
      GANP DNA-primase activity is controlled by phosphorylation at Ser(502) that is
      induced by CD40-mediated signaling in vitro and in the germinal center B cells
      stimulated with antigen in vivo. Overexpression of ganp cDNA in Daudi B cells
      caused the increased DNA synthesis more than the levels of the mock
      transfectants. These evidences suggested that the novel DNA-primase GANP is
      involved in regulation of cell proliferation of antigen-driven B cells in
      germinal centers.

PMID- 11526239
TI  - A combinatorial approach for selectively inducing programmed cell death in human
      pancreatic cancer cells.
AB  - Pancreatic cancer is an extremely aggressive neoplasm whose incidence equals its
      death rate. Despite intensive analysis, the genetic changes that mediate
      pancreatic cancer development and effective therapies for diminishing the
      morbidity associated with this disease remain unresolved. Through subtraction
      hybridization, we have identified a gene associated with induction of
      irreversible growth arrest, cancer reversion, and terminal differentiation in
      human melanoma cells, melanoma differentiation associated gene-7 (mda-7). Ectopic
      expression of mda-7 when using a recombinant adenovirus, Ad.mda-7, results in
      growth suppression and apoptosis in a broad spectrum of human cancers with
      diverse genetic defects, without exerting deleterious effects in normal human
      epithelial or fibroblast cells. Despite the apparently ubiquitous antitumor
      effects of mda-7, pancreatic carcinoma cells are remarkably refractory to Ad.mda
      7 induced growth suppression and apoptosis. In contrast, the combination of
      Ad.mda-7 with antisense phosphorothioate oligonucleotides, which target the K-ras
      oncogene (a gene that is mutated in 85 to 95% of pancreatic carcinomas), induces
      a dramatic suppression in growth and a decrease in cell viability by induction of
      apoptosis. In mutant K-ras pancreatic carcinoma cells, programmed cell death
      correlates with expression and an increase, respectively, in MDA-7 and BAX
      proteins and increases in the ratio of BAX to BCL-2 proteins. Moreover,
      transfection of mutant K-ras pancreatic carcinoma cells with an antisense K-ras
      expression vector and infection with Ad.mda-7 inhibits colony formation in vitro
      and tumorigenesis in vivo in nude mice. These intriguing observations demonstrate
      that a combinatorial approach, consisting of a cancer-specific apoptosis-inducing
      gene and an oncogene inactivation strategy, may provide the foundation for
      developing an effective therapy for pancreatic cancer.

PMID- 11526241
TI  - Variable beta-catenin expression in colorectal cancers indicates tumor
      progression driven by the tumor environment.
AB  - Invasion and dissemination of well-differentiated carcinomas are often associated
      with loss of epithelial differentiation and gain of mesenchyme-like capabilities
      of the tumor cells at the invasive front. However, when comparing central areas
      of primary colorectal carcinomas and corresponding metastases, we again found the
      same differentiated epithelial growth patterns. These characteristic phenotypic
      changes were associated with distinct expression patterns of beta-catenin, the
      main oncogenic protein in colorectal carcinomas, and E-cadherin. Nuclear beta
      catenin was found in dedifferentiated mesenchyme-like tumor cells at the invasive
      front, but strikingly, as in central areas of the primary tumors, was localized
      to the membrane and cytoplasm in polarized epithelial tumor cells in the
      metastases. This expression pattern was accompanied by changes in E-cadherin
      expression and proliferative activity. On the basis of these data, we postulate
      that an important driving force for progression of well-differentiated colorectal
      carcinomas is the specific environment, initiating two transient phenotypic
      transition processes by modulating intracellular beta-catenin distribution in
      tumor cells.

PMID- 11526240
TI  - Molecular emergence of acute myeloid leukemia during treatment for acute
      lymphoblastic leukemia.
AB  - Therapy-related acute myeloid leukemias (t-AML) with translocations of the MLL
      gene are associated with the use of topoisomerase II inhibitors. We established
      the emergence of the malignant clone in a child who developed t-AML with a
      t(11;19) (q23;p13.3) during treatment for acute lymphoblastic leukemia (ALL). The
      MLL-ENL and the reciprocal ENL-MLL genomic fusions and their chimeric transcripts
      were characterized from samples collected at the time of t-AML diagnosis. We used
      PCR with patient-specific genomic primers to establish the emergence of the MLL
      ENL fusion in serially obtained DNA samples. The MLL-ENL fusion was not
      detectable in bone marrow at the time of ALL diagnosis or after 2 months of
      chemotherapy (frequency <8.3 x 10(-7) cells(-1)). The genomic fusion was first
      detected in bone marrow after 6 months of treatment at a frequency of one in
      4,000 mononuclear bone marrow cells; the frequency was one in 70 cells after 20
      months of therapy. At the first detection of MLL-ENL, the only topoisomerase II
      inhibitors the patient had received were one dose of daunorubicin and two doses
      of etoposide. The MLL-ENL fusion was not detectable in blood at the time of ALL
      diagnosis or after 0.7, 2, 8, 10, and 12 months of therapy but was detectable in
      blood at 16 months (one in 2.3 x 10(4) cells). Recombinogenic Alu sequences
      bracketed the breakpoints in both fusions. These data indicate that the malignant
      clone was not present before therapy, arose early during chemotherapy, and was
      able to proliferate even during exposure to antileukemic therapy.

PMID- 11526242
TI  - An anti-angiogenic state in mice and humans with retinal photoreceptor cell
      degeneration.
AB  - Abnormal angiogenesis accompanies many pathological conditions including cancer,
      inflammation, and eye diseases. Proliferative retinopathy because of retinal
      neovascularization is a leading cause of blindness in developed countries.
      Another major cause of irreversible vision loss is retinitis pigmentosa, a group
      of diseases characterized by progressive photoreceptor cell degeneration.
      Interestingly, anecdotal evidence has long suggested that proliferative diabetic
      retinopathy is rarely associated clinically with retinitis pigmentosa. Here we
      show that neonatal mice with classic inherited retinal degeneration
      (Pdeb(rd1)/Pdeb(rd1)) fail to mount reactive retinal neovascularization in a
      mouse model of oxygen-induced proliferative retinopathy. We also present a
      comparable human paradigm: spontaneous regression of retinal neovascularization
      associated with long-standing diabetes mellitus occurs when retinitis pigmentosa
      becomes clinically evident. Both mouse and human data indicate that reactive
      retinal neovascularization either fails to develop or regresses when the number
      of photoreceptor cells is markedly reduced. Our findings support the hypothesis
      that a functional mechanism underlying this anti-angiogenic state is failure of
      the predicted up-regulation of vascular endothelial growth factor, although other
      growth factors may also be involved. Preventive and therapeutic strategies
      against both proliferative and degenerative retinopathies may emerge from this
      work.

PMID- 11526244
TI  - Noninvasive neuroelectronic interfacing with synaptically connected snail neurons
      immobilized on a semiconductor chip.
AB  - A hybrid circuit of a semiconductor chip and synaptically connected neurons was
      implemented and characterized. Individual nerve cells from the snail Lymnaea
      stagnalis were immobilized on a silicon chip by microscopic picket fences of
      polyimide. The cells formed a network with electrical synapses after outgrowth in
      brain conditioned medium. Pairs of neurons were electronically interfaced for
      noninvasive stimulation and recording. Voltage pulses were applied to a
      capacitive stimulator on the chip to excite the attached neuron. Signals were
      transmitted in the neuronal net and elicited an action potential in a second
      neuron. The postsynaptic excitation modulated the current of a transistor on the
      chip. The implementation of the silicon-neuron-neuron-silicon circuit constitutes
      a proof-of-principle experiment for the development of neuroelectronic systems to
      be used in studies on neuronal signal processing, neurocomputation, and
      neuroprosthetics.

PMID- 11526243
TI  - AML1-ETO expression is directly involved in the development of acute myeloid
      leukemia in the presence of additional mutations.
AB  - The t(8;21) is one of the most frequent chromosomal abnormalities associated with
      acute myeloid leukemia (AML). The translocation, which involves the AML1 gene on
      chromosome 21 and the ETO gene on chromosome 8, generates an AML1-ETO fusion
      transcription factor. To examine the effect of the AML1-ETO fusion protein on
      leukemogenesis, we made transgenic mice in which expression of AML1-ETO is under
      the control of the human MRP8 promoter (hMRP8-AML1-ETO). AML1-ETO is specifically
      expressed in myeloid cells, including common myeloid progenitors of hMRP8-AML1
      ETO transgenic mice. The transgenic mice were healthy during their life spans,
      suggesting that AML1-ETO alone is not sufficient for leukemogenesis. However,
      after treatment of newborn hMRP8-AML1-ETO transgenic mice and their wild-type
      littermates with a strong DNA-alkylating mutagen, N-ethyl-N-nitrosourea, 55% of
      transgenic mice developed AML and the other 45% of transgenic mice and all of the
      wild-type littermates developed acute T lymphoblastic leukemia. Our results
      provide direct evidence that AML1-ETO is critical for causing myeloid leukemia,
      but one or more additional mutations are required for leukemogenesis. The hMRP8
      AML1-ETO-transgenic mice provide an excellent model that can be used to isolate
      additional genetic events and to further understand the molecular pathogenesis of
      AML1-ETO-related leukemia.

PMID- 11526245
TI  - An essential role of a TatC homologue of a Delta pH- dependent protein
      transporter in thylakoid membrane formation during chloroplast development in
      Arabidopsis thaliana.
AB  - At least three transport systems function in targeting nuclear-encoded
      chloroplast proteins to the chloroplast thylakoid membrane. One of these systems
      requires a thylakoid pH gradient and is named the DeltapH-dependent protein
      transport system. A similar DeltapH export system of Escherichia coli contains
      four components, twin arginine translocation A (TatA), TatB, TatC, and TatE. TatC
      is a major component of the DeltapH-dependent protein transporter in E. coli and
      functions in the translocation of tightly folded proteins across membranes. We
      have isolated four transposon-inserted albino mutants named albino and pale green
      2 (apg2) from Arabidopsis thaliana and showed that the transposons were inserted
      into different sites of a single gene. The APG2 gene product (named cpTatC) has
      sequence similarity with bacterial TatC and contains six putative transmembrane
      domains, including bacterial TatC proteins and a transit peptide in its N
      terminus. apg2 mutants showed albino phenotypes and could not grow in soil. The
      apg2 plastids were highly vacuolated, lacked internal membrane structures and
      lamellae of the thylakoid membrane, and contained many densely stained globule
      structures, like undifferentiated proplastids. Immunoblot analysis detected no
      thylakoid membrane proteins such as D1, light-harvesting complex, and OE23 in
      apg2 plastids, whereas soluble proteins such as rubisco large and small subunits
      were not decreased. These results indicate an essential role of cpTatC in
      chloroplast development, especially in thylakoid membrane formation.

PMID- 11526247
TI  - Diagnosis Please certificate of recognition awarded again to Sergio Julio
      Moguillansky, MD.

PMID- 11526246
TI  - A genome-wide scan for linkage to human exceptional longevity identifies a locus
      on chromosome 4.
AB  - Substantial evidence supports the familial aggregation of exceptional longevity.
      The existence of rare families demonstrating clustering for this phenotype
      suggests that a genetic etiology may be an important component. Previous attempts
      at localizing loci predisposing for exceptional longevity have been limited to
      association studies of candidate gene polymorphisms. In this study, a genome-wide
      scan for such predisposing loci was conducted by using 308 individuals belonging
      to 137 sibships demonstrating exceptional longevity. By using nonparametric
      analysis, significant evidence for linkage was noted for chromosome 4 at D4S1564
      with a MLS of 3.65 (P = 0.044). The analysis was corroborated by a parametric
      analysis (P = 0.052). These linkage results indicate the likelihood that there
      exists a gene, or genes, that exerts a substantial influence on the ability to
      achieve exceptional old age. Identification of the genes in humans that allow
      certain individuals to live to extreme old age should lead to insights on
      cellular pathways that are important to the aging process.

PMID- 11526248
TI  - Determining costs of imaging services.

PMID- 11526249
TI  - Evidence-based radiology: a new approach to the practice of radiology.
AB  - In this review, the principles of evidence-based health care and their
      application to radiology are discussed. Evidence-based health care involves the
      more formal integration of the best research evidence with clinical expertise and
      explicit acknowledgment of patient values in clinical decision making, as
      compared with conventional practice. Recently, many health care disciplines have
      adopted the principles and practice of evidence-based health care. In radiology,
      including its diagnostic and interventional aspects, these developments have
      received limited attention. This review of evidence-based health care could,
      therefore, be useful to radiologists at any stage of their training or career, to
      encourage the practice of evidence-based radiology. The development of evidence
      based health care is described, and evidence-based health care and evidence-based
      radiology are defined. The importance of evidence-based health care as a new
      approach to the practice of medicine and its importance for transdisciplinary
      collaboration are discussed. The skills required to practice evidence-based
      radiology are identified, and the roles of evidence-based radiology in radiologic
      practice, education, and research are discussed.

PMID- 11526250
TI  - Endovascular versus open surgical elective repair of infrarenal abdominal aortic
      aneurysm: predictors of patient discharge destination.
AB  - PURPOSE: To evaluate patient discharge destination after elective endovascular or
      open surgical repair of infrarenal abdominal aortic aneurysm and to determine
      predictors for discharge to home or to a rehabilitation center. MATERIALS AND
      METHODS: All patients electively treated for infrarenal abdominal aortic aneurysm
      with endovascular repair (n = 182) or open surgery (n = 274) between January 1997
      and September 1999 were included. From the hospital database, information on
      discharge destination, patient characteristics, complications, and length of stay
      was retrieved. Multiple logistic regression analysis was performed to determine
      predictors for discharge to home or to a rehabilitation center. RESULTS: Patient
      characteristics did not differ significantly between the treatment groups, with
      the exception of age (mean age, 75.1 vs 72.9 years in the endovascular and open
      surgical group, respectively; P =.005). Patient discharge destinations differed
      significantly between the treatment groups (P =.001). After endovascular
      procedures, 156 (85.7%) of 182 patients went home and 19 (10.4%) of 182 patients
      went to a rehabilitation center. After open surgery, 187 (68.2%) of 274 patients
      went home and 64 (23.4%) of 274 patients went to a rehabilitation center. The
      odds ratio of discharge to a rehabilitation center, instead of home, following
      endovascular procedures versus open surgery was 0.23 (95% CI: 0.13, 0.43).
      CONCLUSION: Following elective repair of infrarenal abdominal aortic aneurysm,
      significantly more patients went home after an endovascular procedure than after
      open surgery. Procedure type was a significant predictor of discharge
      destination.

PMID- 11526251
TI  - Resource cost analysis of cervical spine trauma radiography.
AB  - PURPOSE: To determine the resource costs of the technical component of cervical
      spine radiography in patients with trauma and the factors that drive resource
      costs, to provide a model for resource cost estimation, and to compare resource
      costs with other methods of cost estimation. MATERIALS AND METHODS: Direct
      measurement was made of technologist labor and supply costs of a cohort of 409
      consecutive patients with trauma who underwent cervical spine radiography.
      Probability of cervical spine injury was determined by reviewing emergency
      department medical records. An animated simulation model was used to combine cost
      and injury probability estimates to determine resource costs. Sensitivity
      analysis explored factors that determined costs and estimated uncertainty in
      model estimations. Comparison was made with other cost estimates. RESULTS: The
      average technical resource cost for cervical spine radiography was $49.60. Both
      direct labor ($19.60 vs $13.33; P <.005) and film ($8.39 vs $6.76; P <.005) costs
      were greater in patients with high probability of injury than in those with low
      probability of injury. Overall costs in patients with high probability of injury
      exceeded those in patients with low probability of injury by 33%. Resource costs
      exceeded Medicare resource-based relative value unit reimbursements for all
      patients with trauma. CONCLUSION: Resource costs of the technical components of
      cervical spine radiography varied with patient probability of injury and were
      higher than Medicare reimbursements.

PMID- 11526253
TI  - MR imaging of the wrist: effect on clinical diagnosis and patient care.
AB  - PURPOSE: To evaluate the effect of magnetic resonance (MR) imaging of the wrist
      on clinicians' diagnoses, diagnostic certainty, and patient care. MATERIALS AND
      METHODS: A controlled observational study was performed. Referring clinicians
      completed questionnaires about diagnosis and intended management before and after
      wrist MR imaging. One hundred eighteen consecutive patients referred for MR
      imaging of the wrist were recruited from the MR imaging units at a regional
      teaching hospital and a large district general hospital. The main measures were
      changes in the clinicians' leading and subsidiary diagnoses after MR imaging,
      their certainty in these diagnoses, and changes in intended patient care.
      RESULTS: Questionnaires were incorrectly completed for five patients,
      questionnaires were not returned for three, appointments were canceled for 10,
      and two could not tolerate the MR examination. Complete follow-up data were
      available for 98 patients. The clinical diagnosis changed in 55 of 98 patients;
      in the remaining 43 patients, diagnostic certainty increased in 23. Clinicians
      reported that MR imaging had substantially improved their understanding of the
      disease in 67 of 98 patients. The care plan changed in 45 of 98 patients, with a
      shift away from surgical treatment. Twenty-eight patients were discharged without
      further investigation. MR imaging was similarly effective in the regional
      teaching center and the district general hospital. CONCLUSION: MR imaging of the
      wrist influences clinicians' diagnoses and management plans.

PMID- 11526254
TI  - Palmar tilt of the distal radius: influence of off-lateral projection  initial
      observations.
AB  - PURPOSE: To evaluate the effect of slight off-lateral positioning of the wrist on
      measurements of the palmar tilt of the distal radius on lateral views and to
      determine how this effect can be corrected quantitatively. MATERIALS AND METHODS:
      Seven cadaveric forearms in neutral and various oblique positions (5 degrees, 10
      degrees, 15 degrees, 20 degrees ) of supination and pronation were examined with
      lateral radiography. The palmar tilt of the distal radius measured on the
      radiographs was correlated with each position of the wrist and the distance
      between the position of the palmar cortex of the pisiform bone (P) and a
      reference point (point 0), which was defined as the midpoint within the interval
      between palmar cortices of the distal scaphoid pole and of the capitate head (P0
      distance). The same measurements were performed on 11 wrists during arthrography.
      RESULTS: The apparent palmar tilt of the distal radius increased with supination
      of the forearm. Regression analysis with the P0 distance as independent and
      palmar tilt as dependent variables resulted in a slope of 0.95 in the seven
      cadaveric wrists and of 0.92 in the 11 wrist arthrograms. The squares of the
      correlation coefficients (R(2)) were 0.89 in cadaveric wrists and 0.69 in 11
      wrist arthrograms. CONCLUSION: Differences in the palmar tilt produced by off
      lateral projections of the wrist can be estimated from the measured difference of
      the P0 distance. A 1-mm difference in the P0 distance corresponds to a difference
      in the palmar tilt of approximately 1 degrees.

PMID- 11526255
TI  - Ulnar nerve dislocation and snapping triceps syndrome: diagnosis with dynamic
      sonography--report of three cases.
AB  - Initial experience with the use of dynamic sonography of the elbow for diagnosing
      ulnar nerve dislocation and snapping triceps syndrome is reported. Cases of three
      consecutive patients who underwent sonographic evaluation of the elbow and
      subsequent open elbow surgery for symptomatic ulnar nerve dislocation were
      reviewed. Dynamic sonography of the elbow was used to aid in the accurate
      diagnosis of and differentiation between ulnar nerve dislocation and snapping of
      the medial triceps muscle.

PMID- 11526256
TI  - Brain atrophy in relapsing-remitting multiple sclerosis: fractional volumetric
      analysis of gray matter and white matter.
AB  - PURPOSE: To determine the fractional brain tissue volume changes in the gray
      matter and white matter of patients with relapsing-remitting multiple sclerosis
      (MS) and to correlate these measurements with clinical disability and total
      lesion load. MATERIALS AND METHODS: Thirty patients with relapsing-remitting MS
      and 25 healthy control subjects underwent magnetic resonance imaging. Fractional
      brain tissue volumes (tissue volume relative to total intracranial volume) were
      obtained from the total segmented gray matter and white matter in each group and
      were analyzed. RESULTS: The fractional volume of white matter versus that of gray
      matter was significantly lower (-6.4%) in patients with MS (P <.0001) than in
      control subjects. Neither gray matter nor white matter fractional volume
      measurements correlated with clinical disability in the patients with MS.
      CONCLUSION: Loss of brain parenchymal volume in patients with relapsing-remitting
      MS is predominantly confined to white matter. Analysis of fractional brain tissue
      volumes provides additional information useful in characterizing MS and may have
      potential in evaluating treatment strategies.

PMID- 11526257
TI  - Effects of ecstasy (MDMA) on the brain in abstinent users: initial observations
      with diffusion and perfusion MR imaging.
AB  - PURPOSE: To evaluate the effects of 3,4-methylenedioxymethamphetamine (MDMA,
      ecstasy) on the human brain by using diffusion and perfusion magnetic resonance
      (MR) imaging. MATERIALS AND METHODS: Eight abstinent ecstasy users and six
      ecstasy nonusers underwent diffusion and perfusion MR imaging. Apparent diffusion
      coefficient and relative cerebral volume maps were reconstructed. Differences in
      apparent diffusion coefficient values and relative cerebral volume ratios between
      the groups were analyzed with the Mann-Whitney-Wilcoxon test. The relationship
      between apparent diffusion coefficient and relative cerebral volume and the
      extent of previous ecstasy use was investigated with Spearman rank correlation.
      RESULTS: Apparent diffusion coefficient values (0.84 vs 0.65 x 10(-5) cm(2)/sec,
      P <.025) and relative cerebral volume ratios (1.22 vs 1.01, P <.025) were
      significantly higher in the globus pallidus of ecstasy users compared with
      nonusers, respectively. Increases in pallidal relative cerebral volume were
      positively correlated with the extent of previous use of ecstasy (rho = 0.73, P
      <.04). CONCLUSION: Ecstasy use is associated with tissue changes in the globus
      pallidus. These findings are in agreement with findings in case reports,
      suggesting that the globus pallidus is particularly sensitive to the effects of
      ecstasy.

PMID- 11526258
TI  - The tau sign.

PMID- 11526259
TI  - Head and neck lesions: characterization with diffusion-weighted echo-planar MR
      imaging.
AB  - PURPOSE: To evaluate whether apparent diffusion coefficients (ADCs) calculated
      from diffusion-weighted echo-planar magnetic resonance (MR) images can be used to
      characterize head and neck lesions. MATERIALS AND METHODS: Diffusion-weighted
      echo-planar MR imaging was performed with a 1.5-T MR unit in 97 head and neck
      lesions in 97 patients. Images were obtained with a diffusion-weighted factor,
      factor b, of 0, 500, and 1,000 sec/mm(2), and an ADC map was constructed. The
      ADCs of lesions, cerebrospinal fluid, and spinal cord were calculated. RESULTS:
      Acceptable images for ADC measurement were obtained in 81 (84%) patients. The
      mean ADC of malignant lymphomas, (0.66 +/- 0.17[SD]) x 10(-3) mm(2)/sec (n = 13),
      was significantly smaller (P <.001) than that of carcinomas. The mean ADC of
      carcinomas, (1.13 +/- 0.43) x 10(-3) mm(2)/sec (n = 36), was significantly
      smaller (P =.002) than that of benign solid tumors. The mean ADC of benign solid
      tumors, (1.56 +/- 0.51) x 10(-3) mm(2)/sec (n = 22), was significantly smaller (P
      =.035) than that of benign cystic lesions, (2.05 +/- 0.62) x 10(-3) mm(2)/sec (n
      = 10). No significant differences were seen in the mean ADC of cerebrospinal
      fluid and of spinal cord among four groups of lesions. When an ADC smaller than
      1.22 x 10(-3) mm(2)/sec was used for predicting malignancy, the highest accuracy
      of 86%, with 84% sensitivity and 91% specificity, was obtained. CONCLUSION:
      Measurement of ADCs may be used to characterize head and neck lesions.

PMID- 11526260
TI  - Minimally invasive surgery for solitary parathyroid adenomas in patients with
      primary hyperparathyroidism: role of US with supplemental CT.
AB  - PURPOSE: To determine the role of ultrasonography (US) with supplemental computed
      tomography (CT) in patients with primary hyperparathyroidism who undergo
      minimally invasive surgery instead of conventional neck exploration. MATERIALS
      AND METHODS: US and CT were performed in 61 consecutive patients with primary
      hyperparathyroidism (part 1) to identify and localize solitary adenomas for
      resection by means of minimally invasive surgery and to provide a surgical road
      map. In part 2, involving 33 consecutive patients, CT was performed only when no
      solitary adenoma was identified with US or for road map information. Minimally
      invasive surgery was considered successful when serum calcium levels normalized
      and remained stable. RESULTS: In part 1, 46 definite solitary adenomas were found
      with US and two additional ones with CT. Minimally invasive surgery was
      successful in 45 patients and failed once. In part 2, US helped identify 23
      solitary adenomas, and CT helped to find one. Minimally invasive surgery was
      successful in 22 patients and failed in two. Combined results in 94 patients
      demonstrated successful minimally invasive surgery in 67 (71%), with 64 of them
      selected with US alone (95% CI: 61, 80). The sensitivity of US in the diagnosis
      of solitary adenoma was 78% (95% CI: 67%, 86%), with a positive predictive value
      of 96% (95% CI: 88%, 99%). CONCLUSION: US examination of patients with primary
      hyperparathyroidism allowed successful selection for minimally invasive surgery
      in more than two-thirds of the cases, with additional CT useful chiefly for
      surgical road mapping.

PMID- 11526261
TI  - Noninvasive MR imaging-guided focal opening of the blood-brain barrier in
      rabbits.
AB  - PURPOSE: To determine if focused ultrasound beams can be used to locally open the
      blood-brain barrier without damage to surrounding brain tissue and if magnetic
      resonance (MR) imaging can be used to monitor this procedure. MATERIALS AND
      METHODS: The brains of 18 rabbits were sonicated (pulsed sonication) in four to
      six locations, with temporal peak acoustic power ranging from 0.2 to 11.5 W.
      Prior to each sonication, a bolus of ultrasonographic (US) contrast agent was
      injected into the ear vein of the rabbit. A series of fast or spoiled gradient
      echo MR images were obtained during the sonications to monitor the temperature
      elevation and potential tissue changes. Contrast material-enhanced MR images
      obtained minutes after sonications and repeated 1-48 hours later were used to
      depict blood-brain barrier opening. Whole brain histologic evaluation was
      performed. RESULTS: Opening of the blood-brain barrier was confirmed with
      detection of MR imaging contrast agent at the targeted locations. The lowest
      power levels used produced blood-brain barrier opening without damage to the
      surrounding neurons. Contrast enhancement correlated with the focal signal
      intensity changes in the magnitude fast spoiled gradient-echo MR images.
      CONCLUSION: The blood-brain barrier can be consistently opened with focused
      ultrasound exposures in the presence of a US contrast agent. MR imaging signal
      intensity changes may be useful in the detection of blood-brain barrier opening
      during sonication.

PMID- 11526262
TI  - Continuous-infusion contrast-enhanced US: in vitro studies of infusion techniques
      with different contrast agents.
AB  - PURPOSE: To evaluate the infusion properties of three ultrasonographic (US)
      contrast agents and to compare different infusion techniques for achieving
      constant signals during harmonic power Doppler US. MATERIALS AND METHODS: In
      vitro studies were performed in a flow phantom. SH U 508A, NC100100, or FS069 was
      continuously infused at clinically usable doses and infusion rates. To assess
      agent-specific physical properties, these agents were administered by using a
      vertically fixed infusion pump and varying infusion start times. The contrast
      agents were administered by also using a horizontally oriented infusion pump that
      was either fixed or continuously rotated to homogenize the agent in the syringe.
      RESULTS: With SH U 508A and NC100100, constant signals were achieved, regardless
      of the infusion modality used. Compared with conventional infusion, the
      continuous homogenization of SH U 508A, although not necessary for signal
      constancy, increased the agent's usefulness (P <.05). With FS069, only continuous
      homogenization yielded constant signals (P <.001). CONCLUSION: Continuous
      infusion of SH U 508A or NC100100 provided constant harmonic power Doppler US
      signals, regardless of the infusion modality used. Because of the special
      physical properties of FS069, only homogenization produced constant harmonic
      power Doppler US signals during continuous infusion of this agent.

PMID- 11526263
TI  - Catheter-related upper extremity deep venous thrombosis in cancer patients: a
      prospective study based on Doppler US.
AB  - PURPOSE: This prospective study extending for more than 3 years had two
      objectives: (a) to use Doppler ultrasonography (US) to estimate the incidence of
      asymptomatic catheter-related upper extremity deep venous thrombosis (DVT) in a
      large population and (b) to study the effect of the catheter position as an
      individual risk factor for catheter-related DVT. MATERIALS AND METHODS: Between
      October 1995 and June 1998, a total of 145 patients who had oropharyngeal tract
      cancer and who were fitted with the same totally implantable central venous
      catheters (CVCs) were included in the study. Follow-up included (a) estimation of
      the position of each catheter tip on a chest radiograph obtained immediately
      after surgery and (b) regular monthly Doppler US screening for catheter-related
      DVT. RESULTS: Seventeen patients developed catheter-related DVT; 13 of them were
      asymptomatic. The mean interval between CVC implantation and detection of
      thrombosis was 42.2 days. Correct positioning of the distal catheter tip was
      associated with a significantly lower rate of catheter-related DVT. Only five of
      87 patients with a correctly positioned distal catheter tip (ie, either in the
      superior vena cava or at the junction between the right atrium and the superior
      vena cava) developed thrombosis, compared with 12 of 26 patients with a misplaced
      catheter (P <.001). The side on which the CVC was implanted did not influence the
      catheter-related DVT rate. CONCLUSION: The rate of asymptomatic catheter-related
      DVT is high and could be lowered with correct initial CVC positioning.

PMID- 11526264
TI  - Do different types of liver lesions differ in their uptake of the microbubble
      contrast agent SH U 508A in the late liver phase? Early experience.
AB  - PURPOSE: To compare the uptake of SH U 508A in different types of liver lesions
      by using stimulated acoustic emission. MATERIALS AND METHODS: Thirty-seven
      patients with characterized lesions (metastasis, n = 17; hepatocellular
      carcinoma, n = 4; hemangioma, n = 9; focal nodular hyperplasia, n = 7) received
      2.5 g SH U 508A. After 5 minutes, stimulated acoustic emission was elicited by
      using a previously described method. Liver and/or lesional differences were
      assessed with videodensitometry (objective conspicuity score), and two observers
      assessed each lesion by using a six-point scale (subjective conspicuity score).
      RESULTS: Metastases and hepatocellular carcinoma had low stimulated acoustic
      emission; median objective conspicuity scores were 70% and 68% (all scores were >
      or =43%), respectively, and subjective conspicuity scores were 2 or higher for
      both observers. Hemangiomas had reduced stimulated acoustic emission, with more
      variability; the median objective conspicuity score was 41% (range, 9%-72%), and
      the median subjective conspicuity scores were 2 (range, 1-4) and 3.5 (range, 1-5)
      for observers 1 and 2, respectively. Focal nodular hyperplasia had stimulated
      acoustic emission comparable to that of the liver in all cases; the median
      objective conspicuity score was -4.7% (all scores were <6%), and the subjective
      conspicuity score was 1 or lower for both observers. This finding completely
      separated focal nodular hyperplasia and malignancies. Significant differences
      were seen between focal nodular hyperplasia and all other lesion types (P < .05).
      CONCLUSION: Strong late-phase lesional uptake of SH U 508A is characteristic of
      focal nodular hyperplasia, is seen in some hemangiomas, and was not observed in
      malignancies.

PMID- 11526265
TI  - Conspicuity of hepatocellular nodular lesions in cirrhotic livers at ferumoxides
      enhanced MR imaging: importance of Kupffer cell number.
AB  - PURPOSE: To correlate the conspicuity of hepatocellular carcinomas and dysplastic
      nodules on ferumoxides-enhanced magnetic resonance (MR) images with the number of
      Kupffer cells in the hepatic lesions, as compared with that in background liver
      in histopathologic findings. MATERIALS AND METHODS: Sixty-nine
      histopathologically proved moderately or poorly differentiated hepatocellular
      carcinomas, 10 well-differentiated hepatocellular carcinomas, and 19 dysplastic
      nodules were retrospectively studied in 68 patients with cirrhosis who underwent
      ferumoxides-enhanced MR imaging. The contrast-to-noise ratio between the nodules
      and surrounding parenchyma was calculated at T2-weighted fast spin-echo imaging,
      and the difference in the number of Kupffer cells between the nodules and
      surrounding hepatic tissue was calculated histopathologically. The results of MR
      imaging and histopathologic examination were correlated. RESULTS: All 69
      moderately or poorly differentiated hepatocellular carcinomas had high contrast
      to-noise ratios at MR imaging and large differences in the number of Kupffer
      cells. Six of the 10 well-differentiated hepatocellular carcinomas had contrast
      to-noise ratios of zero or nearly zero, and five of these had little difference
      in the number of Kupffer cells. All 19 dysplastic nodules had contrast-to-noise
      ratios of zero or nearly zero, and there were virtually no differences in the
      number of Kupffer cells. CONCLUSION: Hepatocellular nodule conspicuity at
      ferumoxides-enhanced MR imaging depends on differences in the number of Kupffer
      cells within a nodule and the surrounding cirrhotic liver; moderately or poorly
      differentiated hepatocellular carcinomas can be distinguished from well
      differentiated hepatocellular carcinomas and dysplastic nodules.

PMID- 11526266
TI  - Recurrent pyogenic cholangitis: comparison between MR cholangiography and direct
      cholangiography.
AB  - PURPOSE: To compare the accuracy of magnetic resonance (MR) cholangiography with
      that of direct cholangiography for the evaluation of recurrent pyogenic
      cholangitis. MATERIALS AND METHODS: Twenty-four patients with recurrent pyogenic
      cholangitis underwent MR cholangiography before surgery, and 18 of these 24 also
      underwent direct cholangiography. Two reviewers evaluated MR cholangiograms and
      direct cholangiograms and focused on identifying intrahepatic ductal dilatation,
      stricture, and calculi, as well as coexistent parenchymal abnormalities, on the
      basis of the classification of the internal lobes and segments of the liver.
      These observations were compared with surgical findings. RESULTS: According to
      examination results in the surgical specimens, 24 patients had 46 segmental
      abnormalities. MR cholangiography depicted all 46 (100%) segments with ductal
      dilatation, 22 (96%) of 23 segments with focal ductal stricture, and 43 (98%) of
      44 segments with ductal calculi. Eighteen patients who underwent direct
      cholangiography had 32 segmental abnormalities according to examination results
      in the surgical specimens. Direct cholangiography depicted 15 (47%) of 32
      segments with ductal dilatation, eight (44%) of 18 segments with focal ductal
      stricture, and 14 (45%) of 31 segments with ductal calculi. CONCLUSION: MR
      cholangiography is superior to direct cholangiography for accurate topographic
      evaluation of recurrent pyogenic cholangitis because it is able to depict all of
      the biliary tree, despite obstruction or stenosis.

PMID- 11526267
TI  - Acute appendicitis: comparison of helical CT diagnosis focused technique with
      oral contrast material versus nonfocused technique with oral and intravenous
      contrast material.
AB  - PURPOSE: To compare the diagnostic accuracy of focused helical computed
      tomography (CT) with orally administered contrast material with that of
      nonfocused helical CT with orally and intravenously administered contrast
      material. MATERIALS AND METHODS: After receiving oral contrast material, 228
      patients with clinically suspected appendicitis underwent focused appendiceal CT
      (5-mm section thickness, 15-cm coverage in the right lower quadrant). Immediately
      thereafter, helical CT of the entire abdomen and pelvis was performed following
      intravenous administration of contrast material (abdomen, 7-mm section thickness;
      pelvis, 5-mm section thickness). Studies were separated and independently
      interpreted by three observers who were blinded to patient names. Diagnoses were
      established by means of surgical and/or clinical follow-up findings. RESULTS:
      Fifty-one (22.4%) of 228 patients had acute appendicitis. Readers diagnosed
      appendicitis with 83.3%, 73.8%, and 71.4% sensitivity and 93.0%, 92.3%, and 97.9%
      specificity with focused nonenhanced appendiceal CT. Readers diagnosed
      appendicitis with 92.9%, 92.9%, and 88.1% sensitivity and 93.7%, 95.1%, and 96.5%
      specificity with nonfocused enhanced CT. Summary areas under the receiver
      operating characteristic curve estimates for focused nonenhanced and nonfocused
      enhanced CT were 0.916 and 0.964, respectively; the differences were
      statistically significant (P <.05) for two of three readers. All readers
      demonstrated higher sensitivities for detecting the inflamed appendix with
      nonfocused enhanced CT. Appendicitis was missed with focused CT in two patients
      whose inflamed appendix was not included in the imaging of the right lower
      quadrant. All readers were significantly more confident in diagnosing alternative
      conditions with nonfocused enhanced CT. CONCLUSION: Diagnostic accuracy of
      helical CT for acute appendicitis improved significantly with use of intravenous
      contrast material.

PMID- 11526268
TI  - Suspected appendicitis in children: focused CT technique for evaluation.
AB  - PURPOSE: To determine the accuracy of a focused computed tomographic (CT)
      technique with oral and intravenous contrast materials for the diagnosis of
      appendicitis. MATERIALS AND METHODS: Ninety-three abdominal-pelvic contrast
      material-enhanced CT scans obtained during 6 years in 54 girls and 39 boys (age
      range, 1-18 years) with right lower quadrant pain were retrospectively reviewed.
      The detected abnormal findings were recorded as being in the region above the
      upper pole of the right kidney, between the upper pole of the right kidney and
      the lower pole of the right kidney (RLP), or below the iliac crest. Sensitivity,
      specificity, and positive and negative predictive values were calculated. chi(2)
      analysis was performed to determine whether there were significant differences
      among patient groups according to region of detected disease. RESULTS: Fifty-five
      scans were abnormal: 38 showed appendicitis; and 17, other diseases. No scans,
      except two that showed pneumonia, had key findings above the RLP. Nineteen scans
      showed key findings between the RLP and the iliac crest. Thirty-three scans had
      diagnostic findings only below the iliac crest. The sensitivity (97%),
      specificity (93%), positive predictive value (90%), and negative predictive value
      (98%) of interpretation with all images for the diagnosis of appendicitis were
      the same as those of interpretation with only the focused images. CONCLUSION: CT
      performed to diagnose appendicitis can be limited to the region below the RLP.

PMID- 11526269
TI  - Knee in early juvenile rheumatoid arthritis: MR imaging findings.
AB  - PURPOSE: To determine the magnetic resonance (MR) imaging findings in the knee in
      early juvenile rheumatoid arthritis. MATERIALS AND METHODS: MR imaging (1.5 T)
      was performed in the more symptomatic knee in 30 children with juvenile
      rheumatoid arthritis with a symptom duration 1 year or less. Conventional, fast
      spin-echo, three-dimensional gradient-echo, and gadolinium-enhanced T1-weighted
      images were assessed. Two radiologists independently read the images, and a third
      resolved disagreements. These images were compared with knee radiographs in 27
      children. RESULTS: Mean maximal synovial thickness was 4.8 mm +/- 2.4 (SD). Mean
      synovial volume was 15.4 mL +/- 10.8. Suprapatellar joint effusions were seen in
      26 (87%) of 30 knees, meniscal hypoplasia in 11 (37%) of 30 knees, and abnormal
      epiphyseal marrow in eight (27%) of 30 knees. Three knees had articular cartilage
      contour irregularity, fissures, and/or thinning. One knee had a bone erosion.
      Knee radiographs showed suprapatellar fullness in 78% of the knees, joint space
      narrowing in one knee, and no bone abnormalities. CONCLUSION: Synovial
      hypertrophy and joint effusions are the most frequent MR imaging findings of
      knees in early juvenile rheumatoid arthritis. Early in the disease,
      radiographically occult cartilage and bone erosions are uncommonly seen at MR
      imaging. The potential relationship of synovitis to cartilage abnormalities
      deserves further study.

PMID- 11526270
TI  - Effect of electrocardiogram triggering on reproducibility of coronary artery
      calcium scoring.
AB  - PURPOSE: To test the hypothesis that computed tomographic (CT) scanning during
      early rather than middle diastole can significantly reduce the interscan
      variability of coronary artery calcium (CAC) scores. MATERIALS AND METHODS: Five
      hundred thirty-eight patients were initially enrolled; 282 of them were found to
      have CAC at electron-beam CT and underwent repeat scanning to measure interscan
      variability with different electrocardiogram (ECG) triggers. Eight patients were
      excluded owing to respiratory motion; thus, 274 asymptomatic patients were
      examined. Patients were randomly assigned to different ECG trigger interval
      groups: 40% (group 1), 50% (group 2), 60% (group 3), and 80% (group 4). Patients
      in whom more than one-third of sections had greater than 10% ECG trigger
      variability were classified in the untriggered group (group 5). Interscan
      variation was compared among all five groups. RESULTS: Interscan variabilities in
      CAC groups 1-5 were 11.5%, 15.3%, 20.3%, 17.4%, and 33.1%, respectively, for
      total calcium area, and 15.0%, 23.3%, 25.6%, 24.0%, and 42.4%, respectively, for
      total calcium score. CAC score variability was reduced by 34%; and calcium area
      variability, by 38% in group 1, as compared with the reduced variabilities in
      group 4 (P <.01 for both measures). Breath holding was adequate in 812 cases, and
      ECG triggering was correct in 790 of cases. CONCLUSION: Study results strongly
      support the use of an ECG trigger of 40% rather than 80% of the R-R interval in
      electron-beam CT calcium studies.

PMID- 11526271
TI  - ECG-gated reconstructed multi-detector row CT coronary angiography: effect of
      varying trigger delay on image quality.
AB  - PURPOSE: To evaluate the effectiveness of electrocardiographically (ECG)-gated
      retrospective image reconstruction for multi-detector row computed tomographic
      (CT) coronary angiography in reducing cardiac motion artifacts and to evaluate
      the influence of heart rate on cardiac image quality. MATERIALS AND METHODS:
      Sixty-five patients with different heart rates underwent coronary CT angiography.
      Raw helical CT data and ECG tracings were combined to retrospectively reconstruct
      at the defined consecutive z position with a temporal resolution of 250 msec per
      section. The starting points of the reconstruction were chosen between 30% and
      80% of the R-R intervals. The relationships between heart rate, trigger delay,
      and image quality were analyzed. RESULTS: Optimal image quality was achieved with
      a 50% trigger delay for the right coronary artery and 60% for the left circumflex
      coronary artery. Optimal image quality for the left anterior descending coronary
      artery was equally obtained at 50% and 60% triggering. A significant negative
      correlation was observed between heart rate and image quality (P <.05). The best
      image quality was achieved when the heart rate was less than 74.5 beats per
      minute. CONCLUSION: To achieve high image quality, the heart rate should be
      sufficiently slow. Selection of appropriate trigger delays and a decreasing heart
      rate are effective to reduce cardiac motion artifacts.

PMID- 11526273
TI  - Case 38: Caroli disease and renal tubular ectasia.

PMID- 11526275
TI  - Nonvascular interventional procedures: analysis of a 10-year database containing
      more than 21,000 cases.
AB  - PURPOSE: To analyze all procedures performed during 10 years in a nonvascular
      interventional practice. MATERIALS AND METHODS: Date, organ location, and type of
      all 21,324 procedures performed between October 1990 and September 2000 were
      recorded in a database; also included were patient age and inpatient or
      outpatient status. Because genitourinary procedures were not included during the
      first 4 years, nephrostomies were added retrospectively. Yearly interventional
      caseload was compared with the department caseload and the assignment of new
      medical record numbers. Trends in individual procedure location and type were
      analyzed, as well as patient age, inpatient status, daily caseloads, and day of
      the week when the procedure was performed. RESULTS: Caseloads have increased
      10.8% per year, exceeding increases in radiology department and hospital
      activity. Abdomen, outside of a specific organ, was the most common location;
      catheter deployment was the most common procedure. Abscess drainage, placement of
      chest tubes, and nephrostomies have increased, but biliary drainages have
      decreased. Inpatients outnumbered outpatients in all years except 1995, but the
      trend was toward an increase in the proportion of outpatients. The average
      patient was 59.6 years old, with average age diminishing. Friday was the busiest
      day, but weekend procedures have increased. CONCLUSION: Nonvascular
      interventional procedures have increased, with more currently being performed on
      weekends.

PMID- 11526274
TI  - Endovascular brachytherapy for prophylaxis against restenosis after long-segment
      femoropopliteal placement of stents: initial results.
AB  - PURPOSE: To evaluate the feasibility, safety, and effectiveness of endovascular
      brachytherapy for the prevention of restenosis after long-segment femoropopliteal
      percutaneous transluminal angioplasty (PTA) and stent implantation. MATERIALS AND
      METHODS: Thirty-three patients (23 men, 10 women; mean age, 66 years) with
      femoropopliteal lesions (mean treated length, 17 cm; range, 4-30 cm) underwent
      PTA and stent implantation followed by brachytherapy with a centering catheter. A
      dose of 14 Gy was delivered to the adventitia by using an iridium 192 source.
      Long-term pharmacotherapy with acetylsalicylic acid was combined with clopidogrel
      for 1 month. Follow-up examinations included measurement of the ankle-brachial
      index, color-coded duplex ultrasonography, and angiography. RESULTS: The overall
      6-month recurrence rate was 30% (10 of 33 arteries). Seven patients developed
      sudden late thrombotic occlusion of the segment with the stent 3.5-6 months after
      stent implantation. Considering the overall results after successful local
      thrombolysis in six of these seven patients, only four (12%) of 33 arteries with
      a stent had in-stent restenosis caused by neointimal hyperplasia. CONCLUSION: The
      study results are promising concerning the possibility of reducing in-stent
      restenosis by means of brachytherapy after long-segment femoropopliteal placement
      of stents. The high incidence of late thrombotic occlusion requires optimization
      of the antithrombotic regimen.

PMID- 11526276
TI  - Carotid arterial stent placement: results and follow-up in 53 patients.
AB  - PURPOSE: To describe the results, complications, and follow-up data after stent
      placement for occlusive internal carotid arterial disease and to compare the
      results with those in the literature. MATERIALS AND METHODS: Carotid arterial
      stent placement was attempted in 57 arteries in 53 patients. Thirty-six (68%) of
      53 patients were symptomatic. Forty-two (79%) of 53 patients had one to three
      clinically important comorbidities and were considered at high risk. All patients
      underwent pre- and postprocedural independent neurologic examinations. Follow-up
      consisted of serial duplex ultrasonography and clinical assessment. RESULTS: The
      immediate technical success rate of stent deployment was 97%. Periprocedurally,
      three (three [5%] of 57 interventions) transient ischemic attacks and three
      (three [5%] of 57 interventions) minor strokes occurred. Two deaths occurred in
      the first 30 days (one myocardial infarction, one renal failure). One ipsilateral
      major stroke occurred 3 weeks after the procedure. The 30-day ipsilateral major
      stroke and death rate was 5% (three of 57 interventions). At 30 days, one of
      three patients with minor stroke had mild residual dysphasia. Treatment remained
      clinically successful in 48 (96%) of 50 patients. The restenosis rate was 4% (two
      patients). CONCLUSION: Carotid arterial stent placement in a high-risk population
      has morbidity and mortality rates comparable to those of carotid endarterectomy
      in a lower risk population. Carotid arterial stent placement can be performed
      with a low restenosis rate.

PMID- 11526277
TI  - Aortic and arterial aneurysms in behcet disease: management with stent-grafts-
      initial experience.
AB  - PURPOSE: To assess the application of stent-grafts in the management of aortic
      and arterial aneurysms in patients with Behcet disease. MATERIALS AND METHODS:
      Nine aneurysms in seven patients were managed with various types of stent-grafts.
      Diagnoses were based on clinical findings. The aortic aneurysms (n = 3) were
      thoracic (n = 1), suprarenal (n = 1), or infrarenal (n = 1). The arterial
      aneurysms (n = 6) were in the right and left subclavian (n = 2), right common
      carotid (n = 2), right brachiocephalic (n = 1), or left common iliac arteries (n
      = 1). A tandem connection of Gianturco stent covered with polytetrafluorethylene
      was placed in three aneurysms, and a balloon-expandable stent was placed in six.
      RESULTS: The stent-graft was successfully placed in all patients. Immediate
      follow-up angiography revealed complete exclusion of the aneurysm in all cases.
      Follow-up computed tomography performed 3 days to 2 weeks later revealed complete
      exclusion and thrombosis of the aneurysm and patency of the stent-graft in six
      patients. In one patient, total occlusion of the artery with a stent occurred due
      to flow disturbance caused by double lesions. During follow-up (range, 6-59
      months; mean, 28 months), the aneurysm resolved and completely regressed in four
      patients. A recurrent aneurysm at the distal margin of previously inserted stent
      graft was successfully managed with an additional stent-graft. CONCLUSION: The
      findings in this initial experience suggest that stent-graft insertion may be a
      safe and effective alternative to surgical treatment of aortic and arterial
      aneurysms in patients with Behcet disease.

PMID- 11526278
TI  - Determination of renal arterial stenosis severity: comparison of pressure
      gradient and vessel diameter.
AB  - PURPOSE: To determine the hemodynamic significance of arteriographically detected
      renal arterial stenosis by obtaining pressure gradients with a miniaturized
      pressure guide wire. MATERIALS AND METHODS: Forty-six renal arterial stenoses in
      38 patients were assessed in terms of severity and then subjected to gradient
      determination before and after angioplasty. The patients (mean age, 63 years) had
      a mean serum creatinine value of 1.3 mg/dL +/- 0.4 (114.9 micromol/L +/- 35.4
      [SD]) and required on average three medications for blood pressure control. The
      mean degree of stenosis diameter was 51% +/- 17 (range, 12%-85%). RESULTS: The
      systolic and mean arterial pressure gradients with and those without
      vasodilatation were highly correlated with stenosis severity, systolic blood
      pressure, and serum creatinine as a curvilinear fit (r = 0.9, P <.01). At 50%
      stenosis severity, the mean pressure gradient was 22 mm Hg. CONCLUSION: Patients
      with a pressure gradient greater than 20 mm Hg should be good candidates for
      renal arterial dilatation, and use of the pressure guide wire will facilitate
      interventional decisions.

PMID- 11526279
TI  - Predictors of prostate carcinoma: accuracy of gray-scale and color Doppler US and
      serum markers.
AB  - PURPOSE: To determine the accuracy of detecting prostate cancer by using (a) gray
      scale and color Doppler transrectal ultrasonography (US), (b) serum and excess
      prostate-specific antigen (PSA) levels, and (c) targeted and sextant transrectal
      US-guided biopsy. The relationship between US-detected neovascularity and tumor
      biologic activity was also evaluated. MATERIALS AND METHODS: Between 1995 and
      1999, 544 patients with elevated PSA levels and/or abnormal digital rectal
      examination underwent transrectal US-guided sextant biopsy and targeted biopsy of
      US abnormalities. Sensitivity, specificity, and accuracy of gray-scale US, color
      Doppler US, targeted biopsy, and PSA and excess PSA were calculated. RESULTS:
      Gray-scale US depicted 78 (41.1%) of 190 cancers, whereas color Doppler US
      depicted 30 (15.8%) additional cancers. Targeted biopsy was used to detect 108
      (56.8%) cancers, whereas sextant biopsy was used to detect 82 (43.2%) additional
      cancers. Although US-visible cancers had a higher Gleason grade than did cancers
      discovered at sextant biopsy (P <.05), 25 of the 66 cancers identified with
      sextant biopsy alone were Gleason grade 6 or higher. Color Doppler US-depicted
      hypervascularity correlated with biologically aggressive tumors. Excess PSA was
      normal in 58 (30.5%) cancers, with an accuracy of 67.3%, resulting in better
      prediction of prostate tumors than with serum PSA level alone. CONCLUSION: Gray
      scale transrectal US, even coupled with color Doppler US, is inadequate for
      prostate carcinoma screening; therefore, targeted biopsy should always be
      accompanied by complete sextant biopsy sampling.

PMID- 11526280
TI  - Endometrial evaluation with transvaginal US and hysterosonography in asymptomatic
      postmenopausal women with breast cancer receiving tamoxifen.
AB  - PURPOSE: To determine performance characteristics of transvaginal ultrasonography
      (US) and hysterosonography for diagnosing endometrial abnormality in asymptomatic
      postmenopausal women with breast cancer receiving tamoxifen. MATERIALS AND
      METHODS: The authors prospectively examined 138 women receiving tamoxifen by
      using transvaginal US, hysterosonography, and office hysteroscopy. The combined
      hysteroscopic-histopathologic diagnosis was the reference standard. Sensitivity,
      specificity, positive and negative predictive values, and likelihood ratios of
      transvaginal US and hysterosonography were calculated. RESULTS: All 138 women
      underwent transvaginal US; 104, successful hysterosonography; and 117, successful
      hysteroscopy. Uterine abnormality was present in 47 (40.2%) of 117 women: 45 with
      polyps and two with submucosal fibroids. Receiver operating characteristic curve
      analysis revealed 6 mm to be the optimal endometrial thickness cutoff for
      diagnosing endometrial abnormalities. When a thickness greater than 6 mm or a
      focal endometrial finding was considered abnormal, transvaginal US had a
      sensitivity of 85.1% and a specificity of 55.7%. In 92 women who completed
      transvaginal US, hysterosonography, and hysteroscopy, hysterosonography was more
      specific (79.2%; P =.008) but not significantly more sensitive (89.7%; P =.508)
      than transvaginal US. When women with abnormal transvaginal US findings were
      further examined with hysterosonography, the sequential combination of
      transvaginal US and hysterosonography was more specific (77.1%) than transvaginal
      US alone (P <.001), without a significant decrease in sensitivity (78.7%; P
      =.25). CONCLUSION: In asymptomatic postmenopausal women receiving tamoxifen, 6 mm
      is the optimal endometrial thickness cutoff for diagnosing endometrial
      abnormalities with transvaginal US. Further examination with hysterosonography
      can improve specificity by reducing the high false-positive rate of transvaginal
      US.

PMID- 11526281
TI  - Estrogen receptor status in primary breast cancer: iodine 123-labeled cis-11beta
      methoxy-17alpha-iodovinyl estradiol scintigraphy.
AB  - PURPOSE: To determine the sensitivity of iodine 123 ((123)I)-labeled cis-11beta
      methoxy-17alpha-iodovinyl estradiol (Z-MIVE) scintigraphy for the detection of
      estrogen receptors in patients with primary breast carcinoma. MATERIALS AND
      METHODS: In 22 patients, estrogen receptor status was assessed with planar
      scintigraphy and single photon emission computed tomography (SPECT) 4 hours after
      the injection of 185 MBq (123)I-labeled Z-MIVE. For histologic and estrogen
      receptor immunohistochemical analysis, breast carcinoma tissue was obtained in
      all patients by means of biopsy or resection of the primary tumor. Two
      experienced physicians semiquantitatively scored the scintigraphic and
      immunohistochemical findings. The uptake ratio at scintigraphy and the
      immunohistologic staining intensity were scored as negative, weak, intermediate,
      or strong. RESULTS: All patients had histologically proven breast cancer.
      Immunohistologic staining for estrogen receptors yielded negative findings in
      four patients and positive findings in 18 (weak staining, n = 2; intermediate
      staining, n = 6; strong staining, n = 10). Planar (123)I-labeled Z-MIVE
      scintigraphic findings were negative in five patients and positive in 17 (weak
      uptake, n = 2; intermediate uptake, n = 10; strong uptake, n = 5), resulting in
      one false-negative finding. Findings at (123)I-labeled Z-MIVE SPECT were negative
      in four patients and positive in 18. The sensitivities of (123)I-labeled Z-MIVE
      scintigraphy for estrogen receptors were 100% with SPECT and 94% with planar
      scintigraphy. The correlation between immunohistologic and planar scintigraphic
      scores of estrogen receptor status was 0.72 (P <.01). CONCLUSION: (123)I-labeled
      Z-MIVE scintigraphy is a sensitive noninvasive tool for the detection of estrogen
      receptors in patients with breast cancer.

PMID- 11526282
TI  - Screening mammography with computer-aided detection: prospective study of 12,860
      patients in a community breast center.
AB  - PURPOSE: To prospectively assess the effect of computer-aided detection (CAD) on
      the interpretation of screening mammograms in a community breast center.
      MATERIALS AND METHODS: Over a 12-month period, 12,860 screening mammograms were
      interpreted with the assistance of a CAD system. Each mammogram was initially
      interpreted without the assistance of CAD, followed immediately by a reevaluation
      of areas marked by the CAD system. Data were recorded to measure the effect of
      CAD on the recall rate, positive predictive value for biopsy, cancer detection
      rate, and stage of malignancies at detection. RESULTS: When comparing the
      radiologist's performance without CAD with that when CAD was used, the authors
      observed the following: (a) an increase in recall rate from 6.5% to 7.7%, (b) no
      change in the positive predictive value for biopsy at 38%, (c) a 19.5% increase
      in the number of cancers detected, and (d) an increase in the proportion of early
      stage (0 and I) malignancies detected from 73% to 78%. CONCLUSION: The use of CAD
      in the interpretation of screening mammograms can increase the detection of early
      stage malignancies without undue effect on the recall rate or positive predictive
      value for biopsy.

PMID- 11526283
TI  - Potential of computer-aided diagnosis to reduce variability in radiologists'
      interpretations of mammograms depicting microcalcifications.
AB  - PURPOSE: To evaluate whether computer-aided diagnosis can reduce interobserver
      variability in the interpretation of mammograms. MATERIALS AND METHODS: Ten
      radiologists interpreted mammograms showing clustered microcalcifications in 104
      patients. Decisions for biopsy or follow-up were made with and without a computer
      aid, and these decisions were compared. The computer was used to estimate the
      likelihood that a microcalcification cluster was due to a malignancy. Variability
      in the radiologists' recommendations for biopsy versus follow-up was then
      analyzed. RESULTS: Variation in the radiologists' accuracy, as measured with the
      SD of the area under the receiver operating characteristic curve, was reduced by
      46% with computer aid. Access to the computer aid increased the agreement among
      all observers from 13% to 32% of the total cases (P <.001), while the kappa value
      increased from 0.19 to 0.41 (P <.05). Use of computer aid eliminated two-thirds
      of the substantial disagreements in which two radiologists recommended biopsy and
      routine screening in the same patient (P <.05). CONCLUSION: In addition to its
      demonstrated potential to improve diagnostic accuracy, computer-aided diagnosis
      has the potential to reduce the variability among radiologists in the
      interpretation of mammograms.

PMID- 11526284
TI  - Benign and malignant breast masses and axillary nodes: evaluation with echo
      enhanced color power Doppler US.
AB  - PURPOSE: To evaluate microbubble contrast enhancement in distinguishing malignant
      from benign breast masses and malignant from benign axillary nodes in patients
      with breast cancer. MATERIALS AND METHODS: Eighty-six patients with 86 breast
      masses and 32 patients with breast cancer (subgroup of 86 patients) with 32
      axillary nodes underwent color power Doppler ultrasonography with and without
      contrast material. Vascular features and contrast material transit times were
      recorded. Nodal enhancement was compared with corresponding primary breast cancer
      enhancement in the subset of 32 patients. RESULTS: Pathologic analysis revealed
      58 breast carcinomas and 28 benign breast lesions and 20 malignant and 12 benign
      axillary nodes in the 32 patients with breast cancer. Breast cancers had a
      greater total number and greater number of peripheral vessels than did benign
      lesions before and after contrast material administration (P <.001). Malignant
      nodes had a greater total number and greater number of peripheral vessels at
      baseline and after contrast enhancement (P <.05), and a longer enhancement
      duration (P =.004) compared with benign nodes. Malignant nodes enhanced more than
      did corresponding primary breast cancers. Postcontrast number of peripheral
      vessels was an independent predictor of primary breast cancer (P <.05), and
      increased number of peripheral vessels after contrast enhancement and enhancement
      duration were independent predictors of nodal malignancy (P <.05). CONCLUSION:
      Primary breast cancers and malignant axillary nodes had a greater total number
      and greater number of peripheral vessels compared with benign breast masses and
      axillary nodes, respectively.

PMID- 11526285
TI  - Peripheral lung adenocarcinoma: correlation of thin-section CT findings with
      histologic prognostic factors and survival.
AB  - PURPOSE: To evaluate the prognostic importance of thin-section computed
      tomographic (CT) findings of peripheral lung adenocarcinomas. MATERIALS AND
      METHODS: The subjects were 127 patients with adenocarcinomas smaller than 3 cm in
      largest diameter who underwent at least a lobectomy with hilar and mediastinal
      lymphadenectomy. The margin characteristics of nodules and the extent of ground
      glass opacity (GGO) within the nodules at preoperative thin-section CT were
      analyzed retrospectively. Regional lymph node metastasis (LNM) and vessel
      invasion (VI) were histologically examined in surgical specimens. Survival curves
      were calculated according to the Kaplan-Meier method. RESULTS: The frequencies of
      LNM (4% [1 of 24]) and VI (13% [three of 24]) in adenocarcinomas with GGO
      components of more than 50% were significantly lower than those with GGO
      components of less than 10% (LNM, P <.05; VI, P <.01). The patients with GGO
      components of more than 50% showed a significantly better prognosis than those
      with GGO components less than 50% (P <.05). All 17 adenocarcinomas smaller than 2
      cm with GGO components of more than 50% were free of LNM and VI, and all these
      patients are alive without recurrence. Coarse spiculation and thickening of
      bronchovascular bundles around the tumors were observed more frequently in tumors
      with LNM or VI than in those without LNM or VI (P <.01). CONCLUSION: Thin-section
      CT findings of peripheral lung adenocarcinomas correlate well with histologic
      prognostic factors.

PMID- 11526286
TI  - Free-breathing cardiac MR imaging: study of implications of respiratory motion-
      initial results.
AB  - The respiratory motion of several anatomic regions (right hemidiaphragm, left
      ventricle of the heart, chest wall, abdominal wall) was investigated during free
      breathing in 10 healthy volunteers by using multinavigator technology and real
      time magnetic resonance (MR) imaging. The respiratory motion shows hysteretic
      effects, which are strongly subject dependent and might have some effect on the
      quality of cardiac MR images.

PMID- 11526287
TI  - Interstitial MR lymphography with gadoterate meglumine: initial experience in
      humans.
AB  - Magnetic resonance (MR) lymphography was performed in five healthy volunteers and
      three patients (two adults and one infant). Subcutaneous administration of
      gadoterate meglumine in the foot allowed visualization of draining lymph vessels
      and nodes. In one patient, an inguinal fluid collection could be characterized as
      a lymphocele. In the infant, a chylothorax was diagnosed. The authors conclude
      that interstitial MR lymphography with commercially available compounds is
      feasible.

PMID- 11526288
TI  - Human knee: in vivo T1(rho)-weighted MR imaging at 1.5 T--preliminary experience.
AB  - A fast spin-echo sequence weighted with a time constant that defines the magnetic
      relaxation of spins under the influence of a radio-frequency field (T1(rho)) was
      used in six subjects to measure magnetic resonance (MR) relaxation times in the
      knee joint with a 1.5-T MR imager. A quantitative comparison of T2- and T1(rho)
      weighted MR images was also performed. Substantial T1(rho) dispersion was
      demonstrated in human articular cartilage, but muscle did not demonstrate much
      dispersion. T1(rho)-weighted images depicted a chondral lesion with 25% better
      signal-difference-to-noise ratios than comparable T2-weighted images. This
      technique may depict cartilage and muscular abnormalities.

PMID- 11526289
TI  - Emergency radiology.

PMID- 11526290
TI  - The specificity of appendiceal outer diameter at US.

PMID- 11526291
TI  - Brachial arterial access.

PMID- 11526297
TI  - Analysis of chord-length distributions.
AB  - A closed-form analytical solution for the inversion of the integral equation
      relating small-angle scattering intensity distributions of two-phase systems to
      chord-length distributions is presented. The result is generalized to arbitrary
      derivatives of higher order of the autocorrelation function and to arbitrary
      projections of the scattering intensity (including slit collimation). This
      inverse transformation offers an elegant way to investigate the impact of certain
      features, e.g. singularities, in the chord-length distribution or its higher
      order derivatives on the scattering curve, e.g. oscillatory components in the
      asymptotic behavior at a large scattering vector. Several examples are discussed.

PMID- 11526298
TI  - On the arithmetic classification of crystal structures.
AB  - An arithmetic criterion for the classification of crystal structures with $n$
      points in their unit cell ('n-lattices') was described by Pitteri & Zanzotto
      [Acta Cryst. (1998), A54 359-373]. In this paper, a systematic analysis of
      monoatomic 2-lattices is given, showing that there exist 29 distinct arithmetic
      types of these structures, some of which share the same space groups. As all
      monoatomic 2-lattices are constituted by a single crystallographic orbit, these
      structures are also classified by the established criterion of Fischer & Koch
      [Koch & Fischer (1975). Acta Cryst. A31, 88-95; Fischer & Koch (1996).
      International Tables for Crystallography, Vol. A. Dordrecht: Kluwer] involving
      the lattice complexes. The two classifications are found to coincide in this
      simplest case. By examination of some examples taken from the allotropes of the
      elements, it is also shown how the arithmetic criterion can be used to classify
      more complex crystals, such as monoatomic 4-lattices. This gives a group
      theoretical framework for distinguishing structures when the space-group
      classification fails to do so, and Fischer & Koch's criterion, as presented in
      the literature, may not be immediately applied.

PMID- 11526299
TI  - Diffraction by the ideal paracrystal.
AB  - A detailed analysis is made of the statistics and diffraction by a general,
      finite, two-dimensional ideal paracrystal. The statistics of the diagonal chain
      through the ideal paracrystal are derived, and the special cases of square and
      hexagonal ideal paracrystals are considered. Expressions for the diffraction are
      derived and characteristics of diffraction patterns are discussed in terms of the
      different parameters of the model for square and hexagonal ideal paracrystals.
      The variation of peak widths with scattering angle along different directions in
      reciprocal space is examined.

PMID- 11526300
TI  - Environmental influence on electron scattering from a molecule.
AB  - The environmental influence on the electron scattering amplitudes of a molecule
      was evaluated by ab initio molecular-orbital calculations. The model system is
      formic acid in various states, i.e. the monomer, hydrogen-bonded dimer and
      ionized formate form. The model electrostatic potentials were calculated either
      in vacuo or with the polarizable continuum model as a simple model of an aqueous
      environment. It was found that charge compensation due to the environment affects
      the scattering amplitudes significantly. The resultant molecular electrostatic
      potential was fitted by six nucleus-centered Gaussians of site/environment
      dependent atomic electrostatic potentials with small residual errors. Therefore,
      the site/environment-dependent atomic electrostatic potentials will give a good
      model for electron crystallography.

PMID- 11526301
TI  - Applications of dynamical diffraction under locally plane wave conditions:
      defects in nearly perfect crystals and X-ray refractometry.
AB  - In a previous paper, the concept of a locally plane wave was explained
      theoretically. In such a configuration, the fringe pattern recorded on the film
      can be considered as a phase analyser. Here the experimental analysis is
      presented, showing examples of interesting applications to X-ray refractometry
      and to the visualization of the strain field around isolated defects.

PMID- 11526302
TI  - The Gummelt decagon as a 'quasi unit cell'.
AB  - Steinhardt, Jeong, Saitoh, Tanaka, Abe & Tsai [Nature (London) (1998), 396, 55
      57] have demonstrated that the structure of decagonal Al-Ni-Co can be built from
      overlapping clusters of a single type. The structure arises from a decoration of
      the decagons of a Gummelt covering. The unit (essentially a decagonal prism) was
      called by Steinhardt et al. a 'quasi unit cell'. In this work, a classification
      scheme is proposed for 'G patterns'--quasiperiodic patterns obtained by
      decorating a decagonal quasi unit cell. The classification makes use of the fact
      that G patterns can also be derived from decoration of a tiling. The tiles are
      analogues, for decagonal quasiperiodic patterns, of the 'asymmetric units' of a
      periodic pattern; they provide a simple mode of description and classification of
      the 'Gummelt-type structures'. Four existing models for decagonal phases are
      considered from this viewpoint.

PMID- 11526303
TI  - Electron crystallographic image-processing investigation and superstructure
      determination for (Pb0.5Sr0.3Cu0.2)Sr2(Ca0.6Sr0.4)Cu2Oy.
AB  - An electron crystallographic image-processing technique based on the combination
      of high-resolution electron microscopy and electron diffraction has been
      developed to investigate the commensurate structural modulation in the high-Tc
      superconductor (Pb0.5Sr0.3Cu0.2)Sr2(Ca0.6Sr0.4)Cu2Oy. After symmetry averaging, a
      structure image was obtained by image deconvolution at the resolution limited by
      that of the electron microscope. Then phase extension was employed to enhance the
      image resolution up to about 1.25 A by means of the electron diffraction data
      corrected with an empirical method. In the final projected potential map, the
      occupational and/or positional modulation is clearly observed for all atoms,
      including oxygen. The key points of determining superstructures by the technique
      are studied and discussed.

PMID- 11526304
TI  - Theoretical investigation of metastable Al2SiO5 polymorphs.
AB  - Using theoretical simulations based on density functional theory within the
      generalized gradient approximation, a series of metastable phase transitions
      occurring in low-pressure Al2SiO5 polymorphs (andalusite and sillimanite) are
      predicted; similar results were obtained using semiclassical interatomic
      potentials within the ionic shell model. Soft lattice modes as well as related
      structural changes are analysed. For sillimanite, an isosymmetric phase
      transition at ca 35 GPa is predicted; an incommensurately modulated form of
      sillimanite can also be obtained at low temperatures and high pressures. The high
      pressure isosymmetric phase contains five-coordinate Si and Al atoms. The origin
      of the fivefold coordination is discussed in detail. Andalusite was found to
      transform directly into an amorphous phase at ca 50 GPa. This study provides an
      insight into the nature of metastable modifications of crystal structures and the
      ways in which they are formed. Present results indicate the existence of a
      critical bonding distance, above which interatomic interactions cannot be
      considered as bonding. The critical distance for the Si-O bond is 2.25 A.

PMID- 11526305
TI  - Sparsity of the normal matrix in the refinement of macromolecules at atomic and
      subatomic resolution.
AB  - The normal matrix in the least-squares refinement of macromolecules is very
      sparse when the resolution reaches atomic and subatomic levels. The elements of
      the normal matrix, related to coordinates, thermal motion and charge-density
      parameters, have a global tendency to decrease rapidly with the interatomic
      distance between the atoms concerned. For instance, in the case of the protein
      crambin at 0.54 A resolution, the elements are reduced by two orders of magnitude
      for distances above 1.5 A. The neglect a priori of most of the normal-matrix
      elements according to a distance criterion represents an approximation in the
      refinement of macromolecules, which is particularly valid at very high
      resolution. The analytical expressions of the normal-matrix elements, which have
      been derived for the coordinates and the thermal parameters, show that the degree
      of matrix sparsity increases with the diffraction resolution and the size of the
      asymmetric unit.

PMID- 11526306
TI  - On integrating direct methods and isomorphous-replacement techniques: triplet
      estimation and treatment of errors.
AB  - The method of joint probability distribution functions has been generalized in
      order to include and treat different sources of error. The probability
      distributions of the isomorphous pairs (E(p), E(d)) and of the two triples
      (E(ph), E(pk), E(ph+k), E(dh), E(dk), E(dh+k)) are obtained, on the assumption
      that the lack of isomorphism and the errors in measurements cumulate on the E(d)
      variables. The conditional distributions of the two-phase and the three-phase
      structure invariants are derived, showing how the reliability of the
      probabilistic estimates depends on the errors.

PMID- 11526307
TI  - The structure of a decagonal Al72Ni20Co8 quasicrystal.
AB  - The structure of a decagonal Al72Ni20Co8 quasicrystal with space group P10(5)/mmc
      has been determined on the basis of a single-crystal X-ray data set using the
      five-dimensional description. The best-fit model structure based on a cluster
      model having lower symmetry than the decagonal symmetry with 103 parameters gives
      wR = 0.045 and R = 0.063 for 449 reflections. The structure is well described by
      the hexagon, boat and star tiling with an edge length of 6.36 A and is very
      consistent with recent high-resolution electron-microscopy images. The refined
      structure is compared with previously discussed model structures including
      cluster-based models having 20 A tenfold symmetric clusters.

PMID- 11526308
TI  - Diffraction of partially coherent X-rays and the crystallographic phase problem.
AB  - This paper proposes a new physical method for the partial solution of the
      crystallographic phase problem by illuminating the crystal with an X-ray beam of
      limited coherence. The diffraction spots broaden and, if the coherence length of
      the incident beam is small enough in all three dimensions, the diffraction
      pattern becomes continuous. Independent information about the structure is then
      available both at the Bragg angles and at angles that do not satisfy the Bragg
      conditions. Under certain conditions, the total information is sufficient to
      solve the crystal structure ab initio. Two prescriptions for producing X-ray
      beams with limited coherence are given.

PMID- 11526309
TI  - Diffraction line profiles from polydisperse crystalline systems.
AB  - Diffraction patterns for polydisperse systems of crystalline grains of cubic
      materials were calculated considering some common grain shapes: sphere, cube,
      tetrahedron and octahedron. Analytical expressions for the Fourier transforms and
      corresponding column-length distributions were calculated for the various crystal
      shapes considering two representative examples of size-distribution functions:
      lognormal and Poisson. Results are illustrated by means of pattern simulations
      for a f.c.c. material. Line-broadening anisotropy owing to the different crystal
      shapes is discussed. The proposed approach is quite general and can be used for
      any given crystallite shape and different distribution functions; moreover, the
      Fourier transform formalism allows the introduction in the line-profile
      expression of other contributions to line broadening in a relatively easy and
      straightforward way.

PMID- 11526310
TI  - Nomenclature of magnetic, incommensurate, composition-changed morphotropic,
      polytype, transient-structural and quasicrystalline phases undergoing phase
      transitions. II. Report of an IUCr Working Group on Phase Transition
      Nomenclature.
AB  - A general nomenclature applicable to the phases that form in any sequence of
      transitions in the solid state has been recommended by an IUCr Working Group
      [Acta Cryst. (1998). A54, 1028-1033]. The six-field notation of the first Report,
      hereafter I, was applied to the case of structural phase transitions, i.e. to
      transformations resulting from temperature and/or pressure changes between two
      crystalline (strictly periodic) phases involving modifications to the atomic
      arrangement. Extensive examples that illustrate the recommendations were
      provided. This second Report considers, within the framework of a similar six
      field notation, the more complex nomenclature of transitions involving magnetic
      phases, incommensurate phases and transitions that occur as a function of
      composition change. Extension of the nomenclature to the case of phases with less
      clearly established relevance to standard schemes of transition in equilibrium
      systems, namely polytype phases, radiation-induced and other transient phases,
      quasicrystalline phases and their transitions is recommended more tentatively. A
      uniform notation for the translational periodicity, propagation vector or
      wavevector for magnetic and/or incommensurate substances is specified. The
      notation adopted for incommensurate phases, relying partly on the existence of an
      average structure, is also consistent with that for commensurate phases in a
      sequence. The sixth field of the nomenclature is used to emphasize the special
      features of polytypes and transient phases. As in I, illustrative examples are
      provided for each category of phase sequence.

PMID- 11526312
TI  - The structure and domain organization of Escherichia coli isocitrate lyase.
AB  - Enzymes of the glyoxylate-bypass pathway are potential targets for the control of
      many human diseases caused by such pathogens as Mycobacteria and Leishmania.
      Isocitrate lyase catalyses the first committed step in this pathway and the
      structure of this tetrameric enzyme from Escherichia coli has been determined at
      2.1 A resolution. E. coli isocitrate lyase, like the enzyme from other
      prokaryotes, is located in the cytoplasm, whereas in plants, protozoa, algae and
      fungi this enzyme is found localized in glyoxysomes. Comparison of the structure
      of the prokaryotic isocitrate lyase with that from the eukaryote Aspergillus
      nidulans reveals a different domain structure following the deletion of
      approximately 100 residues from the larger eukaryotic enzyme. Despite this, the
      active sites of the prokaryotic and eukaryotic enzymes are very closely related,
      including the apparent disorder of two equivalent segments of the protein that
      are known to be involved in a conformational change as part of the enzyme's
      catalytic cycle.

PMID- 11526313
TI  - Structure of lobster apocrustacyanin A1 using softer X-rays.
AB  - The molecular basis of the camouflage colouration of marine crustacea is often
      provided by carotenoproteins. The blue colour of the lobster carapace, for
      example, is intricately associated with a multimacromolecular 16-mer complex of
      protein subunits each with a bound astaxanthin molecule. The protein subunits of
      crustacyanin fall into two distinct subfamilies, CRTC and CRTA. Here, the crystal
      structure solution of the A(1) protein of the CRTC subfamily is reported. The
      problematic nature of the structure solution of the CRTC proteins (both C(1) and
      A(1)) warranted consideration and the development of new approaches. Three
      putative disulfides per protein subunit were likely to exist based on molecular
      homology modelling against known lipocalin protein structures. With two such
      subunits per crystallographic asymmetric unit, this direct approach was still
      difficult as it involved detecting a weak signal from these sulfurs and suggested
      the use of softer X-rays, combined with high data multiplicity, as reported
      previously [Chayen et al. (2000), Acta Cryst. D56, 1064-1066]. This paper now
      describes the structure solution of CRTC in the form of the A(1) dimer based on
      use of softer X-rays (2 A wavelength). The structure solution involved a xenon
      derivative with an optimized xenon L(I) edge f" signal and a native data set. The
      hand of the xenon SIROAS phases was determined by using the sulfur anomalous
      signal from a high-multiplicity native data set also recorded at 2 A wavelength.
      For refinement, a high-resolution data set was measured at short wavelength. All
      four data sets were collected at 100 K. The refined structure to 1.4 A resolution
      based on 60 276 reflections has an R factor of 17.7% and an R(free) of 22.9%
      (3137 reflections). The structure is that of a typical lipocalin, being closely
      related to insecticyanin, to bilin-binding protein and to retinol-binding
      protein. This A(1) monomer or dimer can now be used as a search motif in the
      structural studies of the oligomeric forms alpha- and beta-crustacyanins, which
      contain bound astaxanthin molecules.

PMID- 11526314
TI  - The C1 subunit of alpha-crustacyanin: the de novo phasing of the crystal
      structure of a 40 kDa homodimeric protein using the anomalous scattering from S
      atoms combined with direct methods.
AB  - The previously unknown crystal structure of the C(1) subunit of the carotenoid
      binding protein alpha-crustacyanin has been determined using the anomalous
      scattering available at 1.77 A wavelength to determine the partial structure of
      the S atoms intrinsic to the native protein. The resulting 'heavy-atom' phases,
      in conjunction with near-atomic resolution (d(min) = 1.15 A) data, were then used
      to initiate successful structure determination using a direct-methods approach.
      This is, to the authors' knowledge, the first time such a small anomalous signal
      ( approximately 1%) has been used to aid the determination of a macromolecular
      structure. As well as the structure itself, the methods used during data
      collection and those used in the elucidation of the sulfur 'heavy-atom' partial
      structure are described here. As predicted, the C(1) subunit adopts a tertiary
      structure typical of the lipocalin superfamily: an eight-stranded antiparallel
      beta-barrel with a repeated +1 topology. The beta-barrel has a calyx shape with
      the two molecules in the asymmetric unit interacting in such a way that the open
      ends of each calyx face each other, although they do not form a single elongated
      pocket. A comparison of this structure with those of other members of the
      lipocalin superfamily has allowed speculation as to the nature of carotenoid
      binding by the protein.

PMID- 11526315
TI  - Structure of a pseudo-16-mer DNA with stacked guanines and two G-A mispairs
      complexed with the N-terminal fragment of Moloney murine leukemia virus reverse
      transcriptase.
AB  - The X-ray crystal structure at 2.0 A resolution of a DNA molecule complexed with
      the N-terminal fragment of Moloney murine leukemia virus reverse transcriptase
      (MMLV RT) has been determined. This method allows the study of nucleic acids in a
      unique and largely unfettered environment without the complicated lattice
      interactions typically observed in DNA-only crystal structures. Molecular
      replacement phasing using only the protein provided readily interpretable
      electron density with no model bias for the DNA. The asymmetric unit of the
      structure consists of the protein molecule bound to the blunt end of a DNA 6/10
      mer, which is composed of a six-base strand (5'-GTCGTC-3') and a ten-base strand
      (3'-CAGCAGGGCA-5'), resulting in a six-base-pair duplex with a four-base single
      stranded overhang. In the crystal structure, the bases of the overhang
      reciprocally pair to yield a doubly nicked pseudo-hexadecamer primarily B-form
      DNA molecule. The pairing between the single strands gives two standard (G-C)
      Watson-Crick pairs and two G(anti)-A(anti) mispairs. The mispairs reside in a G-C
      rich environment and the three consecutive guanines on the 10-mer impart
      interesting structural features to the pseudo-hexadecamer, such as the preference
      for a guanine stack, stretching the C-G base pairs flanking the mispair to the
      point of loss of intra-base-pair hydrogen bonding. The DNA was designed for the
      purpose of comparison with a previous structure, which was determined in the same
      crystal lattice. In all of the authors' previous fragment-DNA complexes, the
      nucleotide at the blunt-ended 3'-hydroxyl was a purine. Consistent with the
      proposed mechanistic role of interactions with the 3'-hydroxyl in processive DNA
      synthesis by RT, it was found that a pyrimidine at this position in the DNA makes
      indentical interactions with the strictly conserved Gly191 and the main chain of
      Leu115 of MMLV RT.

PMID- 11526316
TI  - Selenomethionine substitution of orotidine-5'-monophosphate decarboxylase causes
      a change in crystal contacts and space group.
AB  - Orotidine 5'-monophosphate decarboxylase (ODCase) catalyses the decarboxylation
      of orotidine 5'-monophosphate to uridine 5'-monophosphate, the last step in the
      de novo biosynthesis of uridine 5'-monophosphate. In order to determine the
      structure of ODCase from Escherichia coli by the multi-wavelength anomalous
      dispersion technique, both native and SeMet-substituted proteins have been
      produced and purified. During the production of SeMet ODCase, it was observed
      that SeMet was the only amino acid that it was necessary to add to the defined
      medium during expression. SeMet-substituted ODCase in complex with the inhibitor
      1-(5'-phospho-beta-D-ribofuranosyl)barbituric acid crystallizes under similar
      conditions as the native enzyme. In contrast to the native enzyme, where the
      crystals belong to the orthorhombic space group P2(1)2(1)2(1), the SeMet
      substituted enzyme crystallizes in the monoclinic space group P2(1), with a
      quadrupling of the volume of the asymmetric unit. Despite the drastic difference
      in symmetry, the overall crystal packing is effectively identical in the two
      crystal forms. The change in space group appears to originate in differences in
      the crystal contacts near the SeMet and Met residues. These differences can be
      rationalized in terms of SeMet's larger size and hydrophobicity.

PMID- 11526317
TI  - Structure determination of the head-tail connector of bacteriophage phi29.
AB  - The head-tail connector of bacteriophage phi29 is composed of 12 36 kDa subunits
      with 12-fold symmetry. It is the central component of a rotary motor that
      packages the genomic dsDNA into preformed proheads. This motor consists of the
      head-tail connector, surrounded by a phi29-encoded, 174-base, RNA and a viral
      ATPase protein, both of which have fivefold symmetry in three-dimensional cryo
      electron microscopy reconstructions. DNA is translocated into the prohead through
      a 36 A diameter pore in the center of the connector, where the DNA takes the role
      of a motor spindle. The helical nature of the DNA allows the rotational action of
      the connector to be transformed into a linear translation of the DNA. The crystal
      structure determination of connector crystals in space group C2 was initiated by
      molecular replacement, using an approximately 20 A resolution model derived from
      cryo-electron microscopy. The model phases were extended to 3.5 A resolution
      using 12-fold non-crystallographic symmetry averaging and solvent flattening.
      Although this electron density was not interpretable, the phases were adequate to
      locate the position of 24 mercury sites of a thimerosal heavy-atom derivative.
      The resultant 3.2 A single isomorphous replacement phases were improved using
      density modification, producing an interpretable electron-density map. The
      crystallographically refined structure was used as a molecular-replacement model
      to solve the structures of two other crystal forms of the connector molecule. One
      of these was in the same space group and almost isomorphous, whereas the other
      was in space group P2(1)2(1)2. The structural differences between the oligomeric
      connector molecules in the three crystal forms and between different monomers
      within each crystal show that the structure is relatively flexible, particularly
      in the protruding domain at the wide end of the connector. This domain probably
      acts as a bearing, allowing the connector to rotate within the pentagonal portal
      of the prohead during DNA packaging.

PMID- 11526319
TI  - A direct-method ab initio phasing of a protein, cupredoxin amicyanin, at 1.31 A
      resolution.
AB  - The direct-methods program MULTAN88 has been applied successfully to redetermine
      the structure of a protein, cupredoxin amicyanin, containing 808 non-H atom
      sites, one Cu atom and 132 ordered water molecules in the asymmetric unit using
      data at 1.31 A resolution. Starting with initially random phases, useful phase
      sets selected by figures of merit could be obtained from multiple trials. The E
      maps corresponding to the best eight phase sets in order of combined figures of
      merit (CFOM2) revealed a distorted tetrahedral geometry around the Cu site. The
      phase estimates from the metal and a few neighbouring atoms in the initial E map
      corresponding to the set with the highest CFOM2 could be improved by the density
      modification procedure PERP and led to an interpretable electron-density map.

PMID- 11526318
TI  - Structure of staphylococcal enterotoxin C2 at various pH levels.
AB  - The three-dimensional structure of staphylococcal enterotoxin C2 (SEC2), a toxin
      as well as a superantigen, has been determined at various pH levels from two
      different crystal forms, tetragonal (pH 5.0, 5.5, 6.0 and 6.5) and monoclinic (pH
      8.0) at 100 and 293 K, respectively, by the molecular-replacement method.
      Tetragonal crystals belong to space group P4(3)2(1)2, with unit-cell parameters a
      = b = 42.68, c = 289.15 A (at pH 5.0), and monoclinic crystals to space group
      P2(1), with unit-cell parameters a = 43.3, b = 70.6, c = 42.2 A, beta = 90.3
      degrees. SEC2 contains a zinc-binding motif, D+HExxH, and accordingly a Zn atom
      has been identified. The coordination of the zinc ion suggests that it may be
      catalytic zinc rather than structural, but there is so far no biological evidence
      that it possesses catalytic activity. However, superantigen staphylococcal
      exfoliative toxins A and B have been shown to have enzymatic activity after their
      fold was identified to be similar to that of serine protease. The structure and
      its conformation are similar to the previously reported structures of SEC2.
      Though it was expected that the zinc ion may be leached out, as the histidines
      coordinating the zinc ion are expected to be protonated below pH 6.0, zinc is
      present at all pH values. The coordination distances to zinc increase with
      decreasing pH, with the distances being the least at pH 8.0. The results of
      automated model building using the ARP/wARP program for different data sets
      collected at various pH values are discussed.

PMID- 11526320
TI  - Individual interactions influence the crystalline order for membrane proteins.
AB  - The role of contact interactions in the crystallization of membrane proteins was
      assessed by mutation of amino-acid residues on the surface of the reaction center
      from Rhodobacter sphaeroides. Five single-site mutants were constructed, with
      changes in contact regions found in the trigonal and tetragonal forms but not the
      orthorhombic form. Crystallization trials for the tetragonal form yielded either
      no crystals or crystals with an altered morphology, whereas crystals grew in the
      other two forms, indicating that these interactions are essential for the
      stability of the tetragonal crystals. Changes in the structures determined by X
      ray diffraction of trigonal crystals for each mutant were related to the quality
      of the diffraction. Significant differences in the resolution limit of the
      crystals were associated with the loss of specific interactions between
      neighboring proteins. The results suggest that the contact regions are crucial
      for obtaining highly ordered crystals of membrane proteins.

PMID- 11526321
TI  - Crystallization of a complex between human CDK6 and a virus-encoded cyclin is
      critically dependent on the addition of small charged organic molecules.
AB  - Human CDK6 plays an important role in controlling entry into the eukaryotic cell
      cycle. An activated complex of human CDK6 with a viral cyclin from herpesvirus
      saimiri was purified to homogeneity and crystallized using polyethylene glycol
      3350 as precipitant. Crystallization was critically dependent on a narrow range
      of calcium acetate concentration and the presence of sulfo-betaine 201 as
      additive. Crystals belong to the hexagonal space group P6(1)22 or P6(5)22, with
      unit-cell parameters a = b = 70.14, c = 448.77 A, gamma = 120 degrees, and
      diffract X-rays to at least 3.1 A resolution.

PMID- 11526322
TI  - Overexpression, purification, crystallization and data collection of a single
      stranded DNA-binding protein from Sulfolobus solfataricus.
AB  - Single-stranded DNA-binding proteins are recruited when single-stranded DNA is
      exposed by disruption of the duplex. Many important biological processes such as
      DNA replication can only occur when the two strands of the duplex are separated.
      A defining trait of these proteins is the presence of the so-called OB fold. The
      single-stranded DNA-binding protein of the crenarchaeote Sulfolobus solfataricus
      has a number of interesting differences and similarities to both the eubacterial
      and eukaryotic homologues. It has an extended C-terminal tail with significant
      sequence identity to a similar region in the eubacterial protein. However, the
      sequence of the OB fold is much more like the eukaryotic and euryarchaeal
      proteins. The S. solfataricus protein remains a monomer in the absence of DNA but
      rapidly polymerizes upon binding - a behaviour not seen in the Escherichia coli
      protein. The protein has been overexpressed, purified and crystallized. The
      protein crystallizes in two related forms, both having space group P6(1) (or
      P6(5)) with approximate unit-cell parameters a = b = 75, c = 69 A, but the
      crystals are distinguished by their size and morphology. The larger crystals are
      hexagonal bipyramids and are merohedrally twinned, diffracting to 1.34 A with
      diffraction observed to 1.2 A. Smaller needle-like crystals diffract to about 2.0
      A but are not twinned. Molecular-replacement attempts have failed owing to low
      identity with available search models. The structure will be determined by
      multiple-wavelength methods.

PMID- 11526323
TI  - Crystallization and preliminary diffraction studies of native and
      selenomethionine CcmG (CycY, DsbE).
AB  - Disulfide-bond (Dsb) proteins are a family of redox proteins containing a Cys-X-X
      Cys motif. They are essential for disulfide-bond exchange in the bacterial
      periplasm and are necessary for the correct folding and function of many secreted
      proteins. CcmG (DsbE) is a reducing Dsb protein required for cytochrome c
      maturation. Crystals of Bradyrhizobium japonicum CcmG have been obtained that
      diffract X-rays to 1.14 A resolution. The crystals are orthorhombic, space group
      P2(1)2(1)2(1), with unit-cell parameters a = 35.1, b = 48.2, c = 90.2 A.
      Selenomethionine CcmG was expressed without using a methionine auxotroph or
      methionine-pathway inhibition and was purified without reducing agents.

PMID- 11526324
TI  - Crystallization and preliminary crystallographic analysis of the recombinant N
      terminal domain of riboflavin synthase.
AB  - Riboflavin synthase catalyzes the final step in the biosynthesis of riboflavin.
      Animals and humans lack this enzyme, whereas many bacteria and certain yeasts are
      absolutely dependent on endogenous riboflavin synthesis. Riboflavin synthase is
      therefore an attractive target for chemotherapy. The N-terminal domain of
      riboflavin synthase forms a dimer in solution and is capable of strongly binding
      riboflavin. It can serve as a model for the binding site of the native enzyme.
      Structural information obtained from this domain at high resolution will be
      helpful in the determination of the binding mode of riboflavin and thus for the
      development of antimicrobial drugs. Here, the crystallization and preliminary
      crystallographic analysis of the N-terminal domain of riboflavin synthase are
      reported. The crystals belong to the space group C222(1), with unit-cell
      parameters a = 50.3, b = 104.7, c = 85.3 A, alpha = beta = gamma = 90 degrees,
      and diffract to 2.6 A resolution.

PMID- 11526325
TI  - Crystallization and preliminary X-ray analysis of a thermoalkalophilic lipase
      from Bacillus stearothermophilus L1.
AB  - A thermoalkalophilic lipase from Bacillus stearothermophilus L1 (L1 lipase) was
      crystallized in two different crystal forms using a low concentration of the
      enzyme and a calcium-exchange process. The first, needle-like, crystal form,
      which diffracts to about 3.5 A, belongs to the orthorhombic space group
      P2(1)2(1)2(1), with unit-cell parameters a = 67.84, b = 72.96, c = 104.41 A. The
      second, monoclinic, crystal form, which behaves better than the first form for
      crystallographic analyses, belongs to the monoclinic space group C2 and has unit
      cell parameters a = 119.62, b = 85.05, c = 98.36 A, beta = 99.73 degrees. From
      the monoclinic crystals, a native data set and a samarium-derivative data set
      were collected to 2.0 and 2.3 A resolution, respectively. The difference
      Patterson map between the two data sets shows strong heavy-atom peaks, indicating
      that the crystals are suitable for a high-resolution structure determination.

PMID- 11526326
TI  - Crystallization and preliminary X-ray diffraction analysis of the 1,3-1,4-beta-D
      glucanase from Fibrobacter succinogenes.
AB  - The truncated 1,3-1,4-beta-glucanase (1,3-1,4-beta-D-glucan 4-glucanohydrolase;
      E.C. 3.2.1.73) from Fibrobacter succinogenes was crystallized in four different
      forms by the vapour-diffusion method. Form A crystals have the largest trigonal
      P321 unit cell, diffracting to 3.0 A resolution with four to six molecules per
      asymmetric unit. Form B and C crystals belong to the same monoclinic space group
      P2(1), but the form B unit cell is twice as large as the unit cell of form C.
      Form B crystals diffract to 2.5 A resolution and contain four molecules per
      asymmetric unit. Form C crystals diffract to 2.1 A resolution and contain two
      molecules per asymmetric unit. Form D crystals have the smallest orthorhombic
      P2(1)2(1)2(1) unit cell, containing only one molecule per asymmetric unit, and
      diffract beyond 2.1 A resolution. The crystallization conditions for form B and C
      crystals are almost identical, except that form C crystals were grown in the
      presence of 2 mM Ca(2+) ions. It is likely that Ca(2+) directly binds to the
      glucanase, leading to unit-cell shrinkage as observed in other Bacillus glucanase
      crystals. A self-rotation search identified non-crystallographic twofold axes
      that combine with the crystallographic twofold dyads to give 222 symmetry for
      both form A and form B crystals, indicating that the glucanase has a tendency to
      pack in 222 symmetry.

PMID- 11526327
TI  - Purification, crystallization and preliminary X-ray analysis of the Fab fragment
      from MNAC13, a novel antagonistic anti-tyrosine kinase A receptor monoclonal
      antibody.
AB  - The monoclonal antibody MNAC13 is a potent antagonist that prevents the binding
      of nerve-growth factor (NGF) to its tyrosine kinase A receptor (TrkA) in a
      variety of systems. Structural studies of the FabMNAC13 fragment were performed
      to gain insights into the mechanism of action of this potentially therapeutic
      monoclonal antibody. The optimal conditions for crystallization of FabMNAC13 were
      determined. Crystals appeared as prismatic bundles, displayed P2(1)2(1)2(1) space
      group symmetry and diffracted to a resolution of 1.8 A. The unit-cell parameters
      were determined to be a = 52.73, b = 67.55, c = 111.43 A. The data set was 99.5%
      complete. Molecular replacement was performed, resulting in a correlation
      coefficient of 0.55 and an R value of 0.40. The structure refinement is now in
      progress.

PMID- 11526328
TI  - Overexpression, purification, crystallization and data collection on the
      Bordetella pertussis wlbD gene product, a putative UDP-GlcNAc 2'-epimerase.
AB  - The Boredetella pertussis wlbD gene product is a putative uridine-5-diphosphate N
      acetylglucosamine (UDP-GlcNAc) 2'-epimerase involved in Band A lipopolysaccharide
      biosynthesis. The wlbD gene is homologous to Escherichia coli rffE (32%
      identical), an established UDP-GlcNAc 2'-epimerase that is involved in
      enterobacterial common antigen (ECA) formation. The structure of the rffE protein
      reveals an unexpected role for a bound sodium ion in orientating a substrate
      binding alpha-helix in the enzyme active site. Whilst key active-site residues in
      rffE are present in the wlbD sequence, the sodium-binding residues outside the
      active site are absent. This raises questions about the modulation of enzyme
      activity in these two enzymes. The wlbD gene from B. pertussis has been cloned
      and overexpressed in E. coli and the resulting protein has been purified to
      homogeneity. In the current study, crystals of the mutant Gln339Arg wlbD enzyme
      have been obtained by sitting-drop vapour diffusion. Uncomplexed Gln339Arg and
      UDP-GlcNAc complex data sets have been collected in-house on a rotating-anode
      generator to 2.1 A. Combined, the data sets identify the space group as
      P2(1)2(1)2(1), with unit-cell parameters a = 78, b = 91, c = 125 A, alpha = beta
      = gamma = 90 degrees. The asymmetric unit contains two monomers and 53% solvent.

PMID- 11526329
TI  - Crystallization and preliminary X-ray analysis of a depressant insect toxin from
      the scorpion Buthus martensii Karsch.
AB  - Depressant insect toxins are a distinct group of scorpion neurotoxins for which
      no three-dimensional structures are yet available. A depressant insect toxin
      named BmK dITAP3 from the scorpion Buthus martensii Karsch (BmK) has been
      purified and crystallized. Single crystals of dITAP3 grew in the presence of the
      detergent CYMAL-6 using the hanging-drop vapour-diffusion method with ammonium
      sulfate as precipitant. A set of diffraction data to 2.6 A resolution has been
      collected. Preliminary analysis of the diffraction data indicated that the
      crystal belonged to space group R3, with unit-cell parameters a = b = 73.29, c =
      68.90 A, alpha = beta = 90, gamma = 120 degrees. Assuming two molecules in the
      asymmetric unit, the estimated solvent content is 53.4%.

PMID- 11526330
TI  - Crystallization and preliminary X-ray diffraction analysis of a novel trypsin
      inhibitor from seeds of Copaifera langsdorffii.
AB  - A novel trypsin inhibitor isolated from seeds of Copaifera langsdorffii was
      purified to homogeneity and crystallized. Crystals suitable for X-ray analysis
      were grown using the hanging-drop vapour-diffusion method at 291 K in sodium
      acetate buffer at pH values near 4.3 using PEG 4000 as precipitant. The crystals
      presented symmetry compatible with the space group P4(1)2(1)2 or P4(3)2(1)2, with
      unit-cell parameters a = b = 58.71, c = 93.75 A, and diffracted to 1.83 A
      resolution at the synchrotron source.

PMID- 11526331
TI  - Crystallization and preliminary X-ray analysis of NAD kinase from Mycobacterium
      tuberculosis H37Rv.
AB  - NAD kinase from Mycobacterium tuberculosis H37Rv utilizes ATP or inorganic
      polyphosphate [poly(P)] as a phosphoryl donor for the phosphorylation of NAD. The
      enzyme overexpressed in Escherichia coli was purified and crystallized by means
      of the hanging-drop vapour-diffusion method with polyethylene glycol 4000 as the
      precipitant. Preliminary X-ray analysis of the resultant crystals revealed they
      belonged to the monoclinic space group C2 and had unit-cell parameters a = 140.0,
      b = 69.3, c = 106.3 A, beta = 130.1 degrees. The molecular weight of the NAD
      kinase is 35 kDa; assuming that a crystal contains two subunits of the NAD kinase
      in an asymmetric unit, the solvent content V(sol) is 0.62. X-ray diffraction data
      to 2.99 A have been collected from the native crystal.

PMID- 11526332
TI  - Crystallization of the catalytic subunit of Saccharomyces cerevisiae
      acetohydroxyacid synthase.
AB  - Acetohydroxyacid synthase (AHAS; E.C. 4.1.3.18) is the first enzyme in the
      biosynthetic pathway of the branched-chain amino acids isoleucine, leucine and
      valine. It is a thiamin diphosphate-dependent enzyme which catalyses the
      decarboxylation of pyruvate and its condensation with either 2-ketobutyrate or a
      second molecule of pyruvate to give 2-aceto-2-hydroxybutyrate or 2-acetolactate,
      respectively. The enzyme is the target of sulfonylurea and imidazolinone
      herbicides, which act as potent and specific inhibitors. Here, the
      crystallization and preliminary X-ray diffraction analysis of the catalytic
      subunit of Saccharomyces cerevisiae AHAS is reported. Data to 2.7 A resolution
      have been collected using synchrotron radiation (Advanced Photon Source,
      Chicago). Crystals have unit-cell parameters a = 95.8, b = 110.0, c = 178.9 A and
      belong to the space group P2(1)2(1)2(1). Preliminary analysis indicates there is
      one dimer located in each asymmetric unit.

PMID- 11526333
TI  - Cloning, purification, crystallization and preliminary crystallographic analysis
      of Bacillus subtilis LuxS.
AB  - LuxS of Bacillus subtilis is a member of a novel family of proteins with a
      potential role in quorum sensing, controlling important aspects of cellular
      physiology in a range of microbial species. B. subtilis luxS was cloned,
      expressed in Escherichia coli, purified and crystallized using the hanging-drop
      method of vapour diffusion with ammonium sulfate as the precipitant. The crystals
      belong to one of the enantiomorphic space groups P6(1)22 or P6(5)22, with
      approximate unit-cell parameters a = b = 63.6, c = 151.5 A and one subunit in the
      asymmetric unit, corresponding to a packing density of 2.5 A(3) Da(-1). The
      crystals diffract X-rays to at least 1.55 A resolution on a synchrotron-radiation
      source. Determination of the structure will provide insights into the key
      determinants of function of this class of proteins, for which no structures are
      currently available.

PMID- 11526334
TI  - Crystallization and preliminary X-ray diffraction analysis of the light
      harvesting protein phycocyanin from the thermophilic cyanobacterium Synechococcus
      elongatus.
AB  - The crystallization and preliminary crystallographic study of phycocyanin from
      the thermophilic cyanobacterium Synechococcus elongatus is reported. Phycocyanin
      is composed of alpha- and beta-subunits consisting of 162 and 172 amino-acid
      residues, respectively. These associate to form an alphabeta heterodimer, which
      further associates to give a ring-shaped trimer (alphabeta)(3). Two trimers bind
      head-to-head to form a hexamer (alphabeta)(6). Phycocyanin crystals have been
      obtained by the sitting-drop vapour-diffusion method with a precipitant solution
      containing 30%(w/v) PEG 4000 and 100 mM MES pH 7.5-8.0. Using synchrotron
      radiation, the crystals diffract to 2.0 A resolution. They belong to the trigonal
      space group R32, with unit-cell parameters a = b = 186.75 (3), c = 59.75 (4) A,
      alpha = beta = 90, gamma = 120 degrees. Assuming that the crystallographic triad
      is identical to the threefold axis of the hexamer and with three (alphabeta)(6)
      molecules in a unit cell, the calculated molar volume (V(M)) is 2.64 A(3) Da(-1).
      This value corresponds to a solvent content of approximately 53%, with one
      alphabeta heterodimer occupying the asymmetric unit.

PMID- 11526335
TI  - Purification, crystallization and Patterson search of haemoglobin IV from the
      armoured catfish Liposarcus anisitsi.
AB  - Considerable interest is currently focused on fish haemoglobins in order to
      identify the structural basis for their diversity of functional behaviour. The
      armored catfish Liposarcus anisitsi presents accessorial air breathing through a
      modified stomach, which allows this species to survive in waters with low oxygen
      content. The analysis of its haemolysate has shown the presence of four main
      haemoglobins, with this work focusing on haemoglobin IV (LaHb-IV). LaHb-IV was
      crystallized and X-ray diffraction data were collected to 2.4 A resolution using
      a synchrotron-radiation source. The crystal belongs to the orthorhombic space
      group P2(1)2(1)2(1), with unit-cell parameters a = 52.6 (1), b = 104.8 (2), c =
      113.9 (2) A; preliminary structural analysis revealed the presence of one
      tetramer in the asymmetric unit. The structure was determined using the standard
      molecular-replacement technique.

PMID- 11526336
TI  - A novel 40 kDa protein from goat mammary secretions: purification,
      crystallization and preliminary X-ray diffraction studies.
AB  - A novel 40 kDa protein has been purified from dry secretions of the mammary gland
      of goats. The first 15 N-terminal residues were sequenced and showed a sequence
      identity of 30% to a novel 39 kDa whey protein from bovine mammary secretions.
      The protein was crystallized by the microdialysis method. Protein was dissolved
      to a concentration of 40 mg ml(-1) in 0.025 M Tris-HCl pH 8.0 and equilibrated
      with the same buffer containing 19%(v/v) ethanol. The crystals belong to the
      orthorhombic space group P2(1)2(1)2(1), with unit-cell parameters a = 66.1, b =
      107.8, c = 63.2 A and one molecule per asymmetric unit. Intensity data were
      collected to 2.9 A resolution, with a completeness of 95%. Since no similar model
      is available in the protein structure database, heavy-atom derivatives have been
      prepared and three-dimensional structure determination using the isomorphous
      replacement method is in progress.

PMID- 11526337
TI  - Structure of interleukin 4 mutant E9A suggests polar steering in receptor-complex
      formation.
AB  - Interleukin 4 (IL-4) is a pleiotropic cytokine which induces T-cell
      differentiation and class switching of B cells. It therefore plays a central role
      in the development of allergies and asthma. An IL-4 variant in which Glu9 was
      mutated to alanine shows an 800-fold drop in binding affinity towards its high
      affinity receptor chain. As shown by surface plasmon resonance measurements, this
      mostly arises from a decreased association rate. Here, the crystal structure of
      this mutant is reported. It reveals that the protein has a virtually identical
      structure to the wild type, showing that the unusual behaviour of the mutated
      protein is not a consequence of misfolding. The possibility that polar
      interactions in the encounter complex have a steering effect is discussed.

PMID- 11526338
TI  - MAD on threonine synthase: the phasing power of oxidized selenomethionine.
AB  - The use of selenomethionine and anomalous dispersion has become the most widely
      used way of solving the phase problem for de novo protein structure
      determination. In this paper, MAD data collected from oxidized and reduced
      selenomethionine-containing protein are described, and it is shown that oxidized
      selenomethionine has a very strong phasing power and can be efficiently used if
      the oxidation is uniform. The comparison was performed on threonine synthase
      crystals. For example, the phasing power of the oxidized data is doubled for the
      dispersive signal and is 20% stronger for the anomalous signal at the peak
      wavelength. The strength of the anomalous signal can be used to improve the
      signal when a protein contains few methionines or for single anomalous
      dispersion. The oxidation of some selenomethionines shows in the electron-density
      map through the presence of water molecules within hydrogen-bonding distance of
      the putative O atom.

PMID- 11526339
TI  - LISA: an intranet-based flexible database for protein crystallography project
      management.
AB  - The increase in the number of projects carried out in protein crystallography
      laboratories has emphasized the need for effective management of project
      information and data. To meet this need, a flexible web-accessible database for
      protein crystallography project management (LISA) has been developed using the
      open-source software MySQL and PHP4. The database contains information about all
      aspects of structure-determination projects, including primer and plasmid
      sequences, protein expression, purification and crystallization results,
      structure coordinate files and resultant publications. The database web pages
      include links to relevant servers and contain, in addition, tools for processing
      stored information. The software package is freely available.

PMID- 11526340
TI  - Oligosaccharide binding to family 11 xylanases: both covalent intermediate and
      mutant product complexes display (2,5)B conformations at the active centre.
AB  - The glycoside hydrolase sequence-based classification reveals two families of
      enzymes which hydrolyse the beta-1,4-linked backbone of xylan, xylanases, termed
      families GH-10 and GH-11. Family GH-11 xylanases are intriguing in that catalysis
      is performed via a covalent intermediate adopting an unusual (2,5)B (boat)
      conformation, a conformation which also fulfils the stereochemical constraints of
      the oxocarbenium ion-like transition state. Here, the 1.9 A structure of a
      nucleophile, E94A, mutant of the Xyn11 from Bacillus agaradhaerens in complex
      with xylotriose is presented. Intriguingly, this complex also adopts the (2,5)B
      conformation in the -1 subsite, with the vacant space provided by the Glu-->Ala
      mutation allowing the sugar to adopt the alpha-configuration at C1. The structure
      of the covalent 2-deoxy-2-fluoroxylobiosyl-enzyme intermediate has been extended
      to atomic (1.1 A) resolution.

PMID- 11526341
TI  - Histochemical method for characterization of enzyme crystals: application to
      crystals of Torpedo californica acetylcholinesterase.
AB  - Histochemical methods are employed to detect and localize a wide range of
      enzymes. Even though protein crystallographers do not commonly use this
      technique, the extensively used colorimetric reaction of Karnovsky was
      successfully adapted for easy and quick identification of acetylcholinesterase
      crystals. The method relies on the reduction of ferricyanide to ferrocyanide by
      thiocholine, released from acetylthiocholine by enzymatic hydrolysis, followed by
      formation of a cupric ferrocyanide precipitate, and allows rapid differentiation
      between salt and enzyme crystals and between native and inhibited crystals of the
      enzyme.

PMID- 11526343
TI  - GLYCO XVI. XVI International Symposium on Glycoconjugates. August 19-24, 2001.
      The Hague, The Netherlands. Abstracts.

PMID- 11526342
TI  - Map self-validation: improved criteria to resolve the SIR or SAS phase ambiguity.
AB  - A procedure was recently described that used the correlation coefficient (CC)
      agreement between the observed /F(h)/ and their associated unbiased 'omit map'
      extrapolated values /X(h)/ from an initial trial map as the basis for resolving
      the SIR or SAS phase ambiguity. It is noted here that a significant improvement
      in selectivity can be obtained if this agreement is expressed in terms of the
      complex-valued F(h) and X(h). A new scheme is outlined to exploit the weighted
      average of the two SIR or SAS phase choices. This procedure requires six FFTs per
      phase compared with three for the older method that randomly selected either of
      the two permitted phase choices from the Argand diagram as starting values. Trial
      calculations are encouraging for applications as low as 4 A resolution.

PMID- 11526344
TI  - Expression of the alpha1F calcium channel subunit by photoreceptors in the rat
      retina.
AB  - PURPOSE: The CACNA1F gene encodes a voltage-gated calcium channel alpha1 subunit,
      alpha1F, which is expressed in the human retina. Mutations in this gene cause
      incomplete X-linked congenital stationary night blindness (CSNB2). The aim of
      this study was to obtain the sequence of the rat alpha1F cDNA and localize the
      encoded polypeptide in the rat retina. METHODS: The full-length rat alpha1F
      sequence was compiled from sequencing of overlapping alpha1F PCR fragments
      amplified from rat retinal cDNA. Antiserum was raised against a human alpha1F
      peptide. It was found that the human alpha1F peptide used to generate the
      antiserum was conserved at only 11 out of 19 residues in the cloned rat sequence.
      Therefore, antibodies were affinity purified against either the human alpha1F
      peptide or the equivalent rat peptide and used for immunofluorescent staining of
      rat retina sections. RESULTS: The rat alpha1F amino acid sequence was found to be
      91% and 95% identical to the human and mouse alpha1F sequences, respectively.
      Antibodies affinity purified against the human alpha1F peptide stained both the
      outer nuclear layer (ONL) and outer plexiform layer of rat retina sections. In
      contrast, staining with antibodies affinity purified against the corresponding
      rat alpha1F peptide was restricted to the ONL. CONCLUSIONS: The rat alpha1F amino
      acid sequence is highly homologous to the human and mouse sequences. The
      immunohistochemical results indicate the existence of distinct alpha1F isoforms
      or alpha1F-like channels, which are differentially distributed in the cell bodies
      and synaptic terminals of photoreceptors in the rat retina.

PMID- 11526345
TI  - The continuation of the Prevention of Events With Angiotensin-Converting Enzyme
      Inhibition (PEACE) Trial.

PMID- 11526346
TI  - Stent selection in clinical practice: Have clinical trials provided the evidence
      we need?

PMID- 11526347
TI  - Reperfusion therapy for acute myocardial infarction in patients with prior bypass
      surgery.

PMID- 11526348
TI  - On the uniformity of cardiopulmonary exercise testing in chronic heart failure.

PMID- 11526349
TI  - Pounds of prevention: obesity therapy.

PMID- 11526350
TI  - Minimally invasive aortic valve surgery: What is "port access"?

PMID- 11526351
TI  - Inotropic therapy for heart failure: an evidence-based approach.
AB  - BACKGROUND: Agents that increase cardiac contractility (positive inotropes) have
      beneficial hemodynamic effects in patients with acute and chronic heart failure
      but have frequently led to increased mortality when given on a long-term basis.
      Despite this fact, inotropes remain commonly used in the management of heart
      failure. METHODS: We reviewed the available data on short- and long-term inotrope
      use in heart failure, emphasizing high-quality evidence on the basis of
      randomized trials that were powered to address clinical end points. RESULTS:
      Available data suggest that long-term inotropic therapy has a negative impact on
      survival in patients with heart failure, regardless of the agent used. The data
      that inotropic therapy improves quality of life are mixed. High-quality
      randomized evidence is lacking for the use of inotropes for other heart failure
      indications, such as for acute decompensations or as a "bridge to transplant."
      CONCLUSIONS: On the basis of the available evidence, the routine use of inotropes
      as heart failure therapy is not indicated in either the acute or chronic setting.
      Potentially appropriate uses of inotropes include as temporary treatment of
      diuretic-refractory acute heart failure decompensations or as a bridge to
      definitive treatment such as revascularization or cardiac transplantation.
      Inotropes also may be appropriate as a palliative measure in patients with truly
      end-stage heart failure. A model of heart failure pathophysiologic features that
      combines an understanding of both hemodynamic and neurohormonal factors will be
      required to best develop and evaluate novel treatments for advanced heart
      failure.

PMID- 11526352
TI  - Effects of cocaine on the coronary arteries.
AB  - BACKGROUND: A number of studies have documented myocardial ischemia and
      infarction associated with cocaine use. Mismatch between myocardial oxygen supply
      and demand from cocaine-induced vasoconstriction and increased myocardial
      workload are often invoked as the major postulated mechanism by which cocaine
      induces myocardial ischemia. This article reviews the literature studying the
      effects produced by cocaine on the coronary arteries to provide insight into the
      various pathophysiologic mechanisms by which cocaine triggers acute cardiac
      ischemia or infarction. METHODS: We reviewed the published literature describing
      the effects of cocaine on the coronary arteries. A MEDLINE search of English
      language articles published between 1985 and 2000 was performed. Key words
      included coronary arteries, coronary vasoconstriction, vasospasm, coronary
      vasodilation, cardiac vasculature, myocardial ischemia, platelets, thrombosis,
      and cocaine. Both animal and human studies were included. The bibliographies of
      identified articles were also explored for additional sources of information.
      RESULTS: A recreational dose of cocaine increases the heart rate by approximately
      30 beats/min. It also increases the blood pressure by 20/10 mm Hg. These
      increases are modest, are equivalent to mild exercise, and are not believed to be
      sufficient to result in myocardial ischemia in the majority of cases. Animal and
      human studies have documented cocaine-induced early coronary artery vasodilation
      as shown by a decrease in coronary perfusion pressure ranging from 13% to 68%.
      This was followed by a more sustained vasoconstriction demonstrated by a decrease
      in epicardial coronary artery diameter ranging from 5% to 30% with various doses
      of cocaine by various methods of administration. These changes alone are also an
      unlikely explanation for cocaine-induced myocardial ischemia. Therefore neither
      increases in myocardial workload nor hemodynamic changes are sufficient to
      explain cocaine-induced myocardial ischemia. However, evidence also exists that
      cocaine activates platelets and promotes thrombosis, resulting in intracoronary
      thrombus formation. Cocaine may also promote premature and more severe coronary
      atherosclerosis. CONCLUSION: The etiology of cocaine-induced myocardial ischemia
      is complex and is likely to be multifactorial. It appears to be the result of
      coronary artery vasoconstriction, intracoronary thrombosis, and accelerated
      atherosclerosis.

PMID- 11526353
TI  - The late open artery hypothesis--a decade later.
AB  - BACKGROUND: Early reperfusion after myocardial infarction has been proved to
      preserve left ventricular function and reduce mortality. However, a significant
      number of patients have persistent occlusion of the infarct-related artery late
      (days to weeks) after myocardial infarction because of ineligibility for
      thrombolytic therapy, failure of reperfusion, or reocclusion. METHODS: In this
      report we review the data on the potential mechanisms and benefits of late
      reperfusion and present prospective data on the incidence of and current practice
      patterns for the management of persistently occluded infarct-related arteries
      late after myocardial infarction. RESULTS: Although several studies have
      associated late patency of the infarct-related artery with improved long-term
      clinical outcome, they were nonrandomized and reflect selection bias.
      Furthermore, data on late patency from the largest study, Global Utilization of
      Steptokinase and Tissue Plasminogen Activator for Occluded Arteries (GUSTO-I),
      failed to confirm independent benefits of an open infarct-related artery 1 year
      after myocardial infarction. The randomized data on the effects of percutaneous
      transluminal coronary angioplasty for occluded infarct-related arteries late
      after myocardial infarction are limited and inconclusive. CONCLUSIONS: The
      hypothesis that late reperfusion by percutaneous coronary intervention days to
      weeks after myocardial infarction results in improved long-term clinical outcomes
      in asymptomatic patients with occluded infarct-related artery is currently being
      tested in the randomized, multicenter Occluded Artery Trial.

PMID- 11526354
TI  - Pediatric hypertension.

PMID- 11526355
TI  - Hyperlipidemia in children and adolescents.

PMID- 11526356
TI  - Obesity and insulin resistance in young people.

PMID- 11526357
TI  - Does stent design affect probability of restenosis? A randomized trial comparing
      Multilink stents with GFX stents.
AB  - BACKGROUND: Experimental studies have revealed that stent configuration
      influences intimal hyperplasia. The purpose of this study was to evaluate
      clinical outcomes for 2 stent designs in a randomized trial with quantitative
      coronary angiography (QCA) and intravascular ultrasonography (IVUS). METHODS: We
      randomly assigned 100 patients with 107 lesions and symptomatic coronary artery
      disease to deployment of a Multilink stent (Advanced Cardiovascular Systems,
      Guidant, Santa Clara, Calif) or a GFX stent (Applied Vascular Engineering, Santa
      Rosa, Calif) with IVUS guidance. QCA and IVUS studies were performed before and
      after intervention and at follow-up (4.2 +/- 1.0 months). RESULTS: There were no
      significant differences in baseline characteristics and QCA and IVUS parameters
      before and after intervention between the 2 groups. However, minimal lumen
      diameter at follow-up was significantly larger in the Multilink group (2.46 +/-
      0.59 vs 2.08 +/- 0.79 mm, P <.05). Maximal in-stent intimal hyperplasia was
      significantly larger in the GFX group (2.9 +/- 1.7 vs 1.8 +/- 1.2 mm(2), P <.01).
      The restenosis rate differed between the 2 groups (Multilink 4% vs GFX 26%, P
      =.003). In multiple stepwise logistic regression analysis, the only predictor
      that significantly correlated with restenosis was stent type (P <.01). The odds
      ratio for the GFX stent-treated vessels was 18.65 (95% confidence interval 2.10
      165.45). CONCLUSIONS: With deployment of the GFX stent, a thicker neointima
      develops within the stent. Stent configuration may affect clinical outcomes.

PMID- 11526358
TI  - Primary percutaneous coronary interventions in patients with acute myocardial
      infarction and prior coronary artery bypass grafting.
AB  - BACKGROUND: The outcome of patients with previous coronary artery bypass grafting
      (CABG) undergoing primary percutaneous coronary intervention (PCI) for the
      treatment of acute myocardial infarction (AMI) is unclear. We sought to assess
      the outcome of patients with prior CABG undergoing primary PCI for the treatment
      of AMI. METHODS AND RESULTS: Between 1991 and 1997, 1072 patients with AMI
      underwent primary PCI without antecedent thrombolytic therapy at the Mayo Clinic.
      There were 128 patients with previous CABG and 944 without previous CABG.
      Patients with previous CABG were further subdivided according to the treated
      vessel: native vessels (n = 65) and bypass graft (n = 63). Clinical and
      angiographic characteristics and 30-day and 1-year outcomes were evaluated.
      Patients with previous CABG were significantly older and had a higher incidence
      of diabetes, hypertension, and hypercholesterolemia. They had a lower left
      ventricular ejection fraction and were also more likely to have congestive heart
      failure. After 1 year of follow-up, adverse cardiac events (death, MI, CABG, or
      repeat PCI) were significantly greater in patients with prior CABG (49.2% vs
      35.9%, P =.04). With use of multivariate logistic regression analysis to adjust
      for differences in baseline characteristics, the treatment of vein graft was
      independently associated with adverse cardiac events (relative risk 1.48 [95%
      confidence interval 1.07-2.03], P =.02), but a history of prior CABG itself was
      not (relative risk 1.22 [95% confidence interval 0.96-1.56], P =.11).
      CONCLUSIONS: Primary PCI for AMI in patients with previous CABG is associated
      with higher adverse events largely attributable to adverse baseline clinical
      characteristics and the treatment of a vein graft.

PMID- 11526359
TI  - Feasibility of photopheresis to reduce the occurrence of restenosis after
      percutaneous transluminal coronary angioplasty: a clinical pilot study.
AB  - BACKGROUND: Photopheresis was evaluated as a means of preventing restenosis on
      the basis of immune modulation. METHODS: This was a prospective, randomized,
      controlled clinical trial analyzing clinical restenosis at 6 months after
      percutaneous transluminal coronary angioplasty (PTCA). Seventy-eight patients
      with single-vessel angioplasty were randomly assigned to a control group of 41
      patients and a treatment group of 37 patients. At 6 months, there were 72
      evaluable patients: 39 control patients and 33 treated. Twenty-nine control
      patients received balloon PTCA only and 10 patients received stents. Twenty
      treated patients received PTCA only and 13 patients received stents. Baseline
      clinical characteristics of both groups were similar. The treatment group
      received photopheresis for a total of 5 treatments. Primary end points were death
      from any cause, myocardial infarction, ischemia, and repeat revascularization
      procedures. RESULTS: By intention-to-treat analysis, clinical restenosis occurred
      in 27% of control patients versus 8% of treated patients (P =.040, relative risk
      = 0.30). CONCLUSIONS: Photopheresis therapy in patients undergoing balloon PTCA
      with and without stent deployment has been shown to be effective in reducing
      restenosis. The use of photopheresis in such patients merits further
      investigation.

PMID- 11526360
TI  - Value of the Bruce protocol to determine peak exercise oxygen consumption in
      patients evaluated for cardiac transplantation.
AB  - BACKGROUND: Peak exercise oxygen consumption (peak VO2) is an important
      discriminator of survival in patients with systolic heart failure and is used to
      select ambulatory patients for transplantation. The major trials assessing the
      relationship between peak VO2 and survival have used a variety of low-level
      exercise protocols. It is unknown how peak VO2 measured in this patient
      population by the more vigorous Bruce treadmill protocol compares with that
      obtained on less intense protocols. METHODS: We studied 15 patients (50 +/- 12
      years old) with severe heart failure (left ventricular ejection fraction 23.5% +/
      8.6%). Patients randomly performed 3 exercise tests with the Bruce treadmill,
      modified Naughton treadmill, and modified bicycle protocols within 14 days. To
      determine the ability of this patient population to perform the Bruce protocol,
      we also retrospectively analyzed the ability of 84 patients to perform this test
      on their initial evaluations at our center. RESULTS: All patients reached the
      anaerobic threshold (AT) on all 3 protocols. The Bruce and modified Naughton
      treadmill protocols resulted in similar peak VO2 percent predicted peak VO2, and
      VO2 at AT values (17.7 +/- 3.8 mL/kg/min, 57.2% +/- 21.1% and 15.4 +/- 4.1
      mL/kg/min vs 18.0 +/- 4.7 mL/kg/min, 58.1% +/- 22.5% and 15.6 +/- 4.4 mL/kg/min,
      respectively). Peak VO2 and VO2 at AT on both treadmill protocols were higher
      than those obtained with bicycle testing (15.3 +/- 3.1 and 11.8 +/- 3.0
      mL/kg/min, P <.05). Exercise duration was shorter with the Bruce and bicycle
      protocols (6.2 +/- 2.2 and 6.7 +/- 2.4 minutes, respectively) compared with the
      modified Naughton protocol (9.7 +/- 4.3 minutes, both P <.005). In addition, 79
      of the 84 patients (94%) evaluated were able to complete the Bruce protocol and
      reach AT. CONCLUSIONS: The Bruce protocol was more time efficient than the
      modified Naughton protocol and yielded similar peak VO2, percent predicted peak
      VO2, and VO2 at AT values. Bicycle exercise may underestimate peak VO2 values.
      The form of exercise should be considered when assessing peak VO2 criteria for
      transplant listing.

PMID- 11526361
TI  - Minimally invasive aortic valve replacement: echocardiographic and clinical
      results.
AB  - BACKGROUND: Port access has been described for mitral and bypass surgery. The
      purpose of this study was to review the clinical and echocardiographic outcomes
      of aortic valve replacement by use of port access. METHODS: Between 1996 and
      1999, 153 port-access aortic valve replacements were performed at our
      institution. The mean age was 63 years (range 16-91 years); 58% were male. The
      New York Heart Association mean class was III; 18% were in class IV. Thirteen
      percent had diabetes, 42% hypertension, 7% prior transient ischemic episode or
      stroke, 7% lung disease, 3% renal failure, and 13% previous surgery.
      Echocardiograms were obtained after valve replacement in 125 patients (96
      intraoperative transesophageal and 97 transthoracic echoes). RESULTS: Median
      length of stay was 8 days. There were no intraoperative deaths; 10 patients
      (6.5%) died in the postoperative period. Stroke occurred in 4 (2.6%), sepsis in 5
      (3.3%), renal failure in 5 (3.3%), pneumonia in 3 (2%), and wound infection in 1
      (0.7%). Tissue prosthesis was present in 83 and a mechanical prosthesis in 42. No
      or trace regurgitation was seen on 94 of 96 (98%) postbypass intraoperative
      echocardiograms and mild on 2. On follow-up echocardiograms, moderate
      regurgitation was seen in 4 of 97 (4.1%), mild-to-moderate in 2 (2.1%), mild in
      18 (18.6%), and no or trace in 71 (73.2%). Of those who had aortic regurgitation
      on intraoperative or follow-up echocardiograms, it was paravalvular in 8.
      CONCLUSIONS: Minimally invasive aortic valve replacement with a port-access
      approach is feasible, even in high-risk patients. Small incisions, a low
      infection rate, and a short length of stay are attainable. However, the
      complications associated with traditional aortic valve replacement still occur.
      Echocardiography is valuable both for intraoperative monitoring and follow-up of
      this new procedure.

PMID- 11526362
TI  - The role of transesophageal echocardiography in transcatheter closure of secundum
      atrial septal defects by the Amplatzer septal occluder.
AB  - BACKGROUND: Our purpose was to determine the role of transesophageal
      echocardiography (TEE) in the closure of atrial septal defects by the Amplatzer
      septal occluder (ASO) (AGA Medical, Golden Valley, Minn). METHODS: A total of 240
      patients with atrial septal defect (ASD) secundum were examined by transthoracic
      2-dimensional echocardiography (TTE) and TEE to determine the ASD morphologic
      features, diameter, and rims. During transcatheter closure TEE was used for
      determination of the ASD diameter and guidance of the ASO implantation. RESULTS:
      Sixteen (6%) patients were found not suitable for transcatheter closure with TTE,
      35 (14%) with TEE, and 2 during catheterization. Twenty-eight patients (18%) had
      partial or total deficiency of the posterior, inferoanterior, or inferoposterior
      rim, 54 (27%) had a centrally positioned ASD, 92 (46%) had insufficient
      superoanterior rim, and 9 had multiple ASDs, whereas 8 had a septal aneurysm
      associated with a single defect and 4 a multiperforated aneurysm. A total of 170
      patients underwent implantation of ASO. The ASO was correctly positioned in 144
      at the first attempt. In the remainder TEE revealed unstable position of the left
      atrial disk (12), opening of both atrial disks in the left atrium (5), deployment
      of the device through the smaller defect in patients with multiple ASDs (3), and,
      in 1 patient, the device was too small and had to be replaced by a larger one.
      CONCLUSIONS: Morphologic variations of the ASD are common. TEE is crucial for the
      determination of the ASD morphologic features, diameter, and rims, which are
      crucial for proper patient selection. TEE allows precise guiding and positioning
      of the ASO, which is essential for safe and effective transcatheter ASD closure.

PMID- 11526363
TI  - Effects of sibutramine on body weight and serum lipids: a double-blind,
      randomized, placebo-controlled study in 322 overweight and obese patients with
      dyslipidemia.
AB  - BACKGROUND: Cardiovascular risk factors associated with obesity, including
      dyslipidemia, can be improved by weight loss. The main dyslipidemia associated
      with obesity is elevated serum triglyceride and decreased serum high-density
      lipoprotein cholesterol (HDL-C) levels. METHODS: A total of 322 obese patients
      (body mass index > or = 27) with serum triglyceride levels > or = 250 mg/dL and <
      or = 1000 mg/dL and serum HDL-C levels < or = 45 mg/dL (women) and < or = 40
      mg/dL (men) were placed on a step I American Heart Association diet and
      subsequently randomized to sibutramine 20 mg (n = 162) or placebo (n = 160) once
      daily for 24 weeks. RESULTS: Patients taking sibutramine had significantly
      greater mean weight loss than those receiving placebo (-4.9 kg vs -0.6 kg, P < or
      = .05). Forty-two percent of the sibutramine group lost > or = 5% of baseline
      weight and 12% lost > or = 10% compared with 8% and 3%, respectively, of the
      placebo group (P < or = .05). Mean decreases in serum triglyceride levels among
      5% and 10% weight-loss responders in the sibutramine group were 33.4 mg/dL and
      72.3 mg/dL, respectively, compared with an increase of 31.7 mg/dL among all
      patients receiving placebo (P < or = .05). Mean increases in serum HDL-C levels
      for 5% and 10% weight-loss responders in the sibutramine group were 4.9 mg/dL and
      6.7 mg/dL, respectively, compared with an increase of 1.7 mg/dL among all
      patients in the placebo group (P < or = .05). Adverse events and discontinuation
      rates were similar in the sibutramine and placebo groups, although sibutramine
      treated patients had mean increases in systolic and diastolic blood pressure of 2
      to 3 mm Hg relative to placebo. CONCLUSIONS: In overweight and obese patients
      with high serum triglyceride levels and low serum HDL-C levels, treatment with
      sibutramine was associated with significant improvements in body weight and in
      serum triglyceride and HDL-C levels.

PMID- 11526364
TI  - Effect of carvedilol on survival and hemodynamics in patients with atrial
      fibrillation and left ventricular dysfunction: retrospective analysis of the US
      Carvedilol Heart Failure Trials Program.
AB  - BACKGROUND: Atrial fibrillation (AF) is present in a significant number of
      patients with congestive heart failure (CHF) caused by left ventricular
      dysfunction and is associated with significant morbidity and increased mortality
      rates. Thus it is necessary to establish therapy to improve the outcome in this
      high-risk population. METHODS: We conducted a retrospective analysis of data from
      the US Carvedilol Heart Failure Trials Program and identified patients with AF at
      the time of enrollment. In these trials, 1094 patients with at least 3 months of
      heart failure symptoms and an ejection fraction < or = 0.35 were randomly
      assigned to receive carvedilol or placebo in a double-blind, stratified program
      according to performance on an exercise test. RESULTS: One hundred thirty-six
      patients with concomitant AF and CHF were identified during the screening visit
      (84 assigned to carvedilol and 52 to placebo). Therapy with carvedilol resulted
      in a significant improvement in left ventricular ejection fraction (from 23% to
      33% with carvedilol and from 24% to 27% with placebo, P =.001). The physician
      global assessment improved in a greater number of patients treated with
      carvedilol than in those treated with placebo (71% vs 48%, P =.025). A trend
      toward a reduction in the combined end point of death or CHF hospitalization was
      also observed (19% in patients treated with placebo and 7% in patients on
      carvedilol; relative risk, 0.35; 95% confidence interval, 0.12, 1.02; P =.055).
      CONCLUSIONS: In patients with AF complicating CHF, carvedilol significantly
      improves left ventricular ejection fraction and physician global assessment and
      probably reduces the combined end point of CHF hospitalizations or death.

PMID- 11526365
TI  - Challenges of subgroup analyses in multinational clinical trials: experiences
      from the MERIT-HF trial.
AB  - BACKGROUND: International placebo-controlled survival trials (Metoprolol
      Controlled-Release Randomised Intervention Trial in Heart Failure [MERIT-HF],
      Cardiac Insufficiency Bisoprolol Study [CIBIS-II], and Carvedilol Prospective
      Randomized Cumulative Survival trial [COPERNICUS]) evaluating the effects of b
      blockade in patients with heart failure have all demonstrated highly significant
      positive effects on total mortality as well as total mortality plus all-cause
      hospitalization. Also, the analysis of the US Carvedilol Program indicated an
      effect on these end points. Although none of these trials are large enough to
      provide definitive results in any particular subgroup, it is natural for
      physicians to examine the consistency of results across various subgroups or risk
      groups. Our purpose was to examine both predefined and post hoc subgroups in the
      MERIT-HF trial to provide guidance as to whether any subgroup is at increased
      risk, despite an overall strongly positive effect, and to discuss the
      difficulties and limitations in conducting such subgroup analyses. METHODS: The
      study was conducted at 313 clinical sites in 16 randomization regions across 14
      countries, with a total of 3991 patients. Total mortality (first primary end
      point) and total mortality plus all-cause hospitalization (second primary end
      point) were analyzed on a time to first event. The first secondary end point was
      total mortality plus hospitalization for heart failure. RESULTS: Overall, MERIT
      HF demonstrated a hazard ratio of 0.66 for total mortality and 0.81 for mortality
      plus all-cause hospitalization. The hazard ratio of the first secondary end point
      of mortality plus hospitalization for heart failure was 0.69. The results were
      remarkably consistent for both primary outcomes and the first secondary outcome
      across all predefined subgroups as well as for nearly all post hoc subgroups. The
      results of the post hoc US subgroup showed a mortality hazard ratio of 1.05.
      However, the US results regarding both the second primary combined outcome of
      total mortality plus all-cause hospitalization and of the first secondary
      combined outcome of total mortality plus heart failure hospitalization were in
      concordance with the overall results of MERIT-HF. Tests of country by treatment
      interaction (14 countries) revealed a nonsignificant P value of.22 for total
      mortality. The mortality hazard ratio for US patients in New York Heart
      Association (NYHA) class III/IV was 0.80, and it was 2.24 for patients in NYHA
      class II, which is not consistent with causality by biologic gradient. We have
      not been able to identify any confounding factor in baseline characteristics,
      baseline treatment, or treatment during follow-up that could account for any
      treatment by country interaction. Thus we attribute the US subgroup mortality
      hazard ratio to be due to chance. CONCLUSIONS: Just as we must be extremely
      cautious in overinterpreting positive effects in subgroups, even those that are
      predefined, we must also be cautious in focusing on subgroups with an apparent
      neutral or negative trend. We should examine subgroups to obtain a general sense
      of consistency, which is clearly the case in MERIT-HF. We should expect some
      variation of the treatment effect around the overall estimate as we examine a
      large number of subgroups because of small sample size in subgroups and chance.
      Thus the best estimate of the treatment effect on total mortality for any
      subgroup is the estimate of the hazard ratio for the overall trial.

PMID- 11526366
TI  - Carvedilol titration in patients with congestive heart failure receiving
      inotropic therapy.
AB  - BACKGROUND: Carvedilol has been shown to improve morbidity and mortality in
      patients with congestive heart failure (CHF). There are limited data of
      carvedilol use in patients on inotrope therapy. We present our experience with
      carvedilol titration in New York Heart Association (NYHA) class IIIb/IV patients
      stabilized on milrinone therapy, as a nonrandomized study with a parallel control
      group of patients never on inotropes. These patients achieved volume control and
      stabilization of their symptoms during the course of milrinone therapy. METHODS
      AND RESULTS: Seventeen patients in class IIIb/IV CHF (group 1) on intermittent
      intravenous milrinone therapy and 15 patients in class II/IIIa compensated CHF
      (group 2) on standard triple heart failure therapy were titrated on carvedilol.
      Success and adverse events during titration were compared between the 2 groups.
      Fifteen (88%) patients in group 1 and 14 (93%) patients in group 2 were
      successfully titrated on carvedilol over 8.1 +/- 1.8 weeks and 6.7 +/- 2.8 weeks,
      respectively. The target dose of carvedilol (25 or 50 mg twice daily) was
      achieved in 13 (87%) patients (group 1) and 14 (93%) patients (group 2). Seven
      (47%) patients in group 1 and 4 (28%) patients in group 2 had adverse events
      during carvedilol titration. Eight (53%) patients in group 1 were weaned off
      milrinone over a period of 8.4 weeks after carvedilol titration, whereas the rest
      of the patients had reduction in the frequency of infusion. Ten (63%) patients in
      group 1 improved by one or more functional classes. CONCLUSIONS: Patients in NYHA
      class IIIb/IV who are treated with inotropic therapy can be titrated on
      carvedilol after reaching a stable state while on milrinone and standard oral
      drugs. Most of these patients can be successfully weaned off of milrinone or have
      decreased frequency of infusions and demonstrate improved functional status.
      Prospective randomized trials are required to evaluate these observations made in
      a limited number of patients in class IIIb and IV CHF because the combination of
      milrinone and beta-blockers has never been adequately evaluated.

PMID- 11526367
TI  - The role of reperfusion therapy in paced patients with acute myocardial
      infarction.
AB  - BACKGROUND/OBJECTIVE: Our purpose was to evaluate the effectiveness of
      reperfusion therapy among elderly paced patients with acute myocardial infarction
      (MI). Current guidelines make no recommendation for the use of reperfusion
      therapy among patients who have a paced rhythm during MI. METHODS: We evaluated
      1954 Medicare beneficiaries 65 years and older treated for acute MI between 1994
      and 1996 who had a paced rhythm for use of reperfusion therapy. Use of
      reperfusion therapy was evaluated for associations with outcomes by logistic
      regression and Cox proportional hazards models incorporating propensity score
      analysis. RESULTS: Reperfusion therapy was used in 171 (8.8%) patients; 70 were
      treated with primary PTCA and 101 with thrombolytic therapy. Patients who
      received reperfusion therapy had 30-day mortality rates similar to those who did
      not receive reperfusion (26.3% vs 25.7%, P =.87). Multivariate adjustment for
      mortality risk factors and treatment propensity indicated no survival benefit
      associated with reperfusion therapy at 30 days (relative risk [RR] 1.07, 95%
      confidence interval [CI] 0.77-1.43) or long-term follow-up (hazard ratio [HR]
      0.86, 95% CI 0.68-1.10). Mortality risks varied by type of reperfusion therapy.
      Patients treated with primary percutaneous transluminal coronary angioplasty were
      at comparable risk of mortality at 30 days (RR 0.73, 95% CI 0.40-1.23) but at
      lower risk at long-term follow-up (HR 0.60, 95% CI 0.40-0.88). Mortality risks
      were unchanged among patients treated with thrombolytics at 30 days (RR 1.32, 95%
      CI 0.92-1.79) and long-term follow-up (HR 1.08, 95% CI 0.82-1.43). CONCLUSION: We
      find suggestive evidence that primary percutaneous transluminal coronary
      angioplasty provides a long-term survival benefit in the treatment of elderly
      patients with acute MI who have a paced rhythm.

PMID- 11526368
TI  - Antiarrhythmic drug use in the implantable defibrillator arm of the
      Antiarrhythmics Versus Implantable Defibrillators (AVID) Study.
AB  - BACKGROUND: Previous retrospective or observational series suggest that many
      patients with an implantable cardioverter-defibrillator (ICD) will be treated
      with antiarrhythmic drugs (AADs) to modify the frequency or manifestation of
      recurrent ventricular arrhythmias. The relative clinical benefit, however, is
      uncertain, and deleterious interactions can occur. The objective of this clinical
      investigation was to study the need for, and effects of, concomitant AAD use with
      the ICD in a prospectively defined cohort. METHODS: All patients randomly
      assigned to the ICD arm of the Antiarrhythmics Versus Implantable Defibrillators
      (AVID) study were followed for the addition of class I or III AADs ("crossover")
      after hospital discharge. Addition of AADs was strictly regulated by AVID
      protocol. The timing and reasons for crossover and the effects on ventricular
      arrhythmia recurrence were analyzed. Patients were excluded if they required AADs
      before hospital discharge after index arrhythmias or if they had no ventricular
      arrhythmia before initiation of AADs. RESULTS: After a median follow-up of 135
      days, 81 (18%) of the 461 eligible patients required AADs and formed the
      crossover group. The primary reason for crossover was frequent ICD shocks in 64%
      of patients. The most common AAD selected was amiodarone (in 42%). Independent
      predictors of crossover were lower ejection fraction, absence of ventricular
      fibrillation, or presence of nonsyncopal ventricular tachycardia at presentation,
      prior unexplained syncope, female sex, and history of cigarette smoking. Before
      AAD use, the 1-year arrhythmia event rate was 90%; after AAD, the event rate was
      only 64% (P =.0001). The time to first event was extended from 3.9 +/- 0.7 months
      to 11.2 +/- 1.8 months. There were 1.4 +/- 3.7 fewer ICD therapy events (P =.005)
      after crossover, predominantly accounted for by reduction in shocks rather than
      antitachycardia pacing therapies. CONCLUSIONS: The majority of patients who
      receive ICDs for sustained ventricular tachycardia or ventricular fibrillation
      can be treated without AADs. Most commonly, AADs are added to combat frequent ICD
      shocks, which are successfully reduced by AAD therapy.

PMID- 11526369
TI  - The natural history of Wolff-Parkinson-White syndrome in 228 military aviators: a
      long-term follow-up of 22 years.
AB  - BACKGROUND: Wolff-Parkinson-White (WPW) syndrome poses a risk for
      tachyarrhythmias and sudden cardiac death. Most WPW studies have relatively
      limited numbers of subjects and brief follow-up periods. METHODS: We reviewed
      records of 238 consecutive military aviators with WPW syndrome evaluated from
      1955 to 1999. Follow-up was by questionnaires, telephone interviews, or death
      certificates. Events included sudden cardiac death and supraventricular
      tachycardia (SVT) (by electrocardiographic [ECG] documentation or suggestive
      symptoms). RESULTS: The mean age was 34.3 years (range 17-56 years). Forty-two
      (42/238, 17.6%) had SVT (WPW syndrome) and 196 of 238 (82.4%) had the WPW ECG
      pattern only. The mean follow-up of 21.8 years (range 2-41 years) was obtained on
      228 of 238 (96%) for a total of 4906 patient-years. Sudden cardiac death occurred
      in 1 of 228, an incidence of 0.0002 per patient-year (95% confidence interval 0.0
      0.001). SVT occurred in 47 of 228 (20.6%) or 0.01 per patient-year. One hundred
      eighty-seven (187/228, 82%) initially had the WPW ECG pattern only; 28 of 187
      (15.0%) reported SVT during follow-up. Forty-one (41/228, 18%) initially had WPW
      syndrome; 19 of 41(46.3%) reported additional SVT during follow-up. CONCLUSION:
      Sudden cardiac death risk was low (0.02%/patient-year) in this WPW population.
      The SVT incidence was 1% per patient-year. Referral bias and some characteristics
      of the unique military aviator population may partly account for these low event
      rates. However, these results may be more applicable to unselected populations
      than are tertiary referral-based studies.

PMID- 11526370
TI  - Cost-effectiveness of beta-blocker therapy with metoprolol or with carvedilol for
      treatment of heart failure in Canada.
AB  - OBJECTIVE: The purpose of this study was to estimate the cost-effectiveness of
      beta-blocker therapy with either metoprolol or carvedilol in addition to
      conventional therapy for patients with heart failure (HF) in Canada. DESIGN: A
      Markov simulation was used to estimate the costs and life expectancy for treating
      patients with conventional therapy alone and with the addition of metoprolol or
      carvedilol. Although carvedilol has been marketed in Canada since 1999,
      metoprolol succinate has yet to be marketed there, so the price is unknown.
      Therefore we input a Canadian price based on the price ratio of the 2 drugs in
      the United States. RESULTS: For subjects aged 60 years at HF onset, the expected
      years of life are 4.53 years for those treated with conventional therapy alone,
      5.70 years for those who receive conventional therapy plus metoprolol, and 6.21
      years for those who receive conventional therapy plus carvedilol. The expected
      costs (in 1999 Canadian dollars) are $8,989, $13,833, and $18,114, respectively.
      This yields incremental cost-effectiveness ratios (ICERs) for metoprolol relative
      to conventional therapy alone of $4,140 per life-year gained, and for carvedilol
      relative to metoprolol, the ICER is $8,394 per life-year gained. CONCLUSIONS: In
      addition to conventional therapy with furosemide and angiotensin converting
      enzyme inhibitors, treatment with either metoprolol or carvedilol confers a
      survival benefit that is attractive from a cost-effectiveness point of view.
      Until better information becomes available, it is not possible to distinguish
      between the two beta-blockers on the basis of cost-effectiveness. This means that
      the choice of beta-blockers for HF should be based largely on clinical
      considerations because both beta-blockers prolong life at relatively low cost.

PMID- 11526371
TI  - Percutaneous closure with Amplatzer device is a safe and efficient alternative to
      surgery in adults with large atrial septal defects.
AB  - BACKGROUND: In adults with atrial septal defect (ASD) and large right-to-left
      shunt, closure of the defect is recommended. Percutaneous closure is still rarely
      used in this population. This study presents the results of transcatheter closure
      with the Amplatzer occluder in such patients. METHODS AND RESULTS: We studied 44
      consecutive adult patients with a secundum ASD and 2 of the 3 following criteria:
      QP/QS >/=2 by oximetry, echocardiographic right ventricle overload, and ASD size
      >20 mm. Forty-two patients had a successful implantation. In 1 patient an
      unstable device was withdrawn; in another one, the device embolized in the
      pulmonary artery. At 6-month median follow-up, 95% had a complete closure; 2
      patients with an additional defect had a small residual shunt. Major
      complications were the aforementioned embolization and a cerebrovascular accident
      in a patient with atrial fibrillation treated with aspirin. Others were minor and
      transitory: premature atrial beats in 3 patients, and paroxysmal atrial
      fibrillation and pulmonary edema in 1 patient each. CONCLUSIONS: Transcatheter
      closure of large ASDs with the Amplatzer device is efficient with less morbidity
      than surgical closure.

PMID- 11526372
TI  - Evaluation of arterial stiffness in children with Williams syndrome: Does it play
      a role in evolving hypertension?
AB  - BACKGROUND: Pathologic studies and surgical observations of thickened aortic
      walls have suggested an increase in aortic stiffness in patients with Williams
      syndrome. However, in vivo objective evaluation of aortic and arterial stiffness
      in Williams syndrome are lacking. Moreover, systemic hypertension, although
      prevalent in Williams syndrome, does not have a well-defined mechanism in this
      syndrome. Therefore, the purpose of this study was to quantitate aortic stiffness
      and arterial compliance in an objective manner, as well as to determine their
      roles in development of hypertension, in children with Williams syndrome.
      METHODS: We studied 13 patients with Williams syndrome (aged 3-12 years) and 16
      age-matched control subjects. Aortic stiffness was calculated from the beta index
      as follows: beta = (ln[P(s)/P(d)])/ ([D(s) - D(d)]/D(d)), where P(s) and P(d) are
      systolic and diastolic blood pressures and D(s) and D(d) are systolic and
      diastolic aortic dimensions, respectively. Arterial compliance (C) was calculated
      by the area method: C= (A(d) x CO x CL) / (A(t) x [P(es) - P(d)]), where A(t) is
      the total area and A(d) is the area under the diastolic portion of the arterial
      pulse tracing, CO is the cardiac output, CL is the cycle length, and P(es) is
      aortic end-systolic pressure. RESULTS: In patients with Williams syndrome, the
      beta index was 2-fold higher than in control patients (9.02 +/- 3.15 vs 4.43 +/-
      0.96, P <.005). Moreover, there was a strong positive correlation between the
      beta index and the systolic blood pressure (r = 0.8 and P <.0001). Compliance was
      decreased by 42% (0.41 +/- 0.11 vs 0.71 +/- 0.10 mL/mm Hg, P <.05), suggesting
      decreased arterial compliance. CONCLUSIONS: Our study indicates that in vivo
      arterial stiffness is increased in patients with Williams syndrome. We speculate
      that increased arterial stiffness may be the predisposing cause of systemic
      hypertension in Williams syndrome.

PMID- 11526373
TI  - Time course of left ventricular remodeling after stentless aortic valve
      replacement.
AB  - BACKGROUND: Stentless aortic valves are associated with a significant decrease in
      left ventricular hypertrophy. This study examined the time course and factors
      affecting left ventricular mass regression (LVMR) after aortic valve replacement
      (AVR) with Cryolife O'Brien (CLOB) (Cryolife International, Atlanta, Ga)
      stentless valves. METHODS: Between 1993 and 2000, 130 consecutive patients
      underwent AVR with CLOB. Mean age was 71.3 +/- 6.3 years. Sixty-four (49.2%) were
      male. Mean body surface area (BSA) was 1.7 +/- 0.2 m(2). Mean valve size
      implanted was 23.6 +/- 2.0 mm. All patients were monitored with serial
      echocardiograms; the first study was performed preoperatively, and subsequent
      controls were at 6 months, 1, 2, 3, 4, 5, 6, and 7 years, respectively. Left
      ventricular mass was calculated by the Devereux formula and indexed by BSA.
      RESULTS: Analysis of variance showed a significant reduction in the left
      ventricular mass index (LVMI) over time (P < .001). Most LVMRs occurred within
      the first 6 months, and after 1 year LVMI had decreased by 37.5% with further,
      but not statistically significant, reductions at later examinations. We found
      that baseline BSA > 1.75 m(2), male sex, arterial blood pressure > or = 150 mm
      Hg, left ventricular ejection fraction < or = 35%, New York Heart Association
      functional class > or = III, non-sinus rhythm, and prevalent aortic incompetence
      to be factors influencing LVMR. LVMR was not related to postoperative effective
      orifice area < or = 0.85 cm/m(2) and prosthetic size. CONCLUSIONS: AVR with a
      CLOB valve is followed by a significant LVMR that occurs soon after surgery. It
      is influenced by several patient-related factors: most of them can be predicted
      preoperatively.

PMID- 11526374
TI  - Blockade of adenosine receptors with aminophylline limits ischemic
      preconditioning in human beings.
AB  - BACKGROUND: Ischemic preconditioning is characterized by the limitation of
      infarct size or ischemic signs after one or more brief episodes of ischemia, a
      process that probably involves stimulation of adenosine receptors. One human
      model of ischemic preconditioning is repetitive occlusion of a coronary artery
      during angioplasty. By using this method of inducing ischemia, we tested the
      hypothesis that blockade of adenosine receptors with aminophylline would abolish
      ischemic preconditioning in human beings. METHODS: Twenty-six patients undergoing
      angioplasty were randomly assigned to receive either aminophylline (6 mg/kg IV)
      or placebo before repetitive coronary occlusion (two 2-minute occlusions
      separated by 5 minutes). ST-segment changes on the surface electrocardiogram were
      used as a measure of myocardial ischemia. Serum theophylline levels and the
      conduction response to an intravenous bolus of adenosine were used to assess the
      efficacy of adenosine receptor blockade. RESULTS: Repetitive coronary occlusion
      resulted in a reduction in ST-segment shift in 9 of 13 patients given placebo. In
      contrast, 9 of 13 patients receiving aminophylline had an increase in ST-segment
      shift on the second occlusion (P =.002). Patients receiving aminophylline (mean
      serum theophylline level of 8.38 +/- 0.45 mg/dL) did not have significant
      conduction block with intravenous adenosine. CONCLUSIONS: Repetitive coronary
      occlusion reduces the signs of ischemia in human beings, a process limited by
      blockade of adenosine receptors.

PMID- 11526376
TI  - T cell regulation: a special job or everyone's responsibility?

PMID- 11526377
TI  - Autoimmune diseases: genes, bugs and failed regulation.

PMID- 11526378
TI  - Multiple sclerosis: a two-stage disease.

PMID- 11526379
TI  - Systemic lupus erythematosus: an autoimmune disease of B cell hyperactivity.

PMID- 11526380
TI  - Type 1 diabetes.

PMID- 11526381
TI  - Determinants of autoimmune thyroid disease.

PMID- 11526382
TI  - Pathogenesis of arthritis: recent research progress.

PMID- 11526384
TI  - Sex differences in autoimmune disease.

PMID- 11526385
TI  - Lessons from animal models for human autoimmune diseases.

PMID- 11526386
TI  - Immunotherapy of multiple sclerosis: where are we? Where should we go?

PMID- 11526387
TI  - The risk of autoimmunity associated with tumor immunotherapy.

PMID- 11526388
TI  - Autoimmunity and lymphoma: tribulations of B cells.

PMID- 11526390
TI  - The genetics of complex autoimmune diseases: non-MHC susceptibility genes.
AB  - Susceptibility to complex autoimmune diseases (AIDs) is a multigenic phenotype
      affected by a variety of genetic and environmental or stochastic factors. After
      over a decade of linkage analyses, the identification of non-major
      histocompatibility complex (non-MHC) susceptibility alleles has proved to be
      difficult, predominantly because of extensive genetic heterogeneity and possible
      epistatic interactions among the multiple genes required for disease development.
      Despite these difficulties, progress has been made in elucidating the genetic
      mechanisms that influence the inheritance of susceptibility, and the pace of gene
      discovery is accelerating. An intriguing new finding has been the colocalization
      of several AID susceptibility genes in both rodent models and human linkage
      studies. This may indicate that several susceptibility alleles affect multiple
      AIDs, or alternatively that genomic organization has resulted in the clustering
      of many immune system genes. The completion of the human genome sequence, coupled
      with the imminent completion of the mouse genome, should yield key information
      that will dramatically enhance the rate of gene discovery in complex conditions
      such as AID susceptibility.

PMID- 11526389
TI  - Autoimmunity provoked by infection: how good is the case for T cell epitope
      mimicry?
AB  - Autoimmune diseases remain one of the mysteries that perplex immunologists. What
      makes the immune system, which has evolved to protect an organism from foreign
      invaders, turn on the organism itself? A popular answer to this question involves
      the lymphoid network's primordial function: autoimmunity is a by-product of the
      immune response to microbial infection. For decades there have been tantalizing
      associations between infectious agents and autoimmunity: beta-hemolytic
      streptococci and rheumatic fever; B3 Coxsackieviruses and myocarditis;
      Trypanosoma cruzi and Chagas' disease; diverse viruses and multiple sclerosis;
      Borrelia burgdorfii and Lyme arthritis; and B4 Coxsackievirus, cytomegalovirus or
      rubella and type 1 diabetes, to name the most frequently cited examples. In
      addition, animal models have provided direct evidence that infection with a
      particular microbe can incite a particular autoimmune disease. Nonetheless, many
      of the associations appear less than convincing and, even for those that seem to
      be on solid footing, there is no real understanding of the underlying
      mechanism(s).

PMID- 11526391
TI  - Tolerogenic strategies to halt or prevent type 1 diabetes.
AB  - A variety of therapeutic strategies have been developed to tolerize autoreactive
      T cells and prevent autoimmune pathology. In terms of type 1 diabetes, prevention
      strategies can inhibit the priming and expansion of autoreactive T cells;
      however, a cure for diabetes would require tolerance to be established in the
      presence of primed effector cells together with replacement of the destroyed beta
      cell mass. Replacement of beta cells could be accomplished by transplantation of
      islets or stem cells or through islet regeneration. We will focus here on
      tolerogenic strategies that have been used to prevent onset of type 1 diabetes
      and discuss the potential for a cure.

PMID- 11526392
TI  - Regulatory T cells in the control of immune pathology.
AB  - It is now well established that regulatory T (T(R)) cells can inhibit harmful
      immunopathological responses directed against self or foreign antigens. However,
      many key aspects of T(R) cell biology remain unresolved, especially with regard
      to their antigen specificities and the cellular and molecular pathways involved
      in their development and mechanisms of action. We will review here recent
      findings in these areas, outline a model for how T(R) cells may inhibit the
      development of immune pathology and discuss potential therapeutic benefits that
      may arise from the manipulation of T(R) cell function.

PMID- 11526393
TI  - "Decisions, decisions.": beta-catenin-mediated activation of TCF-1 and Lef-1
      influences the fate of developing T cells.

PMID- 11526394
TI  - Location, location, location: the cell biology of immunoglobulin allelic control.

PMID- 11526395
TI  - The functional genomics experience (are you experienced?).

PMID- 11526396
TI  - TIRAP: how Toll receptors fraternize.

PMID- 11526397
TI  - A new job for dendritic cells.

PMID- 11526399
TI  - TIRAP: an adapter molecule in the Toll signaling pathway.
AB  - Mammalian Toll-like receptors (TLRs) recognize conserved products of microbial
      metabolism and activate NF-kappa B and other signaling pathways through the
      adapter protein MyD88. Although some cellular responses are completely abolished
      in MyD88-deficient mice, TLR4, but not TLR9, can activate NF-kappa B and mitogen
      activated protein kinases and induce dendritic cell maturation in the absence of
      MyD88. These differences suggest that another adapter must exist that can mediate
      MyD88-independent signaling in response to TLR4 ligation. We have identified and
      characterized a Toll-interleukin 1 receptor (TIR) domain-containing adapter
      protein (TIRAP) and have shown that it controls activation of MyD88-independent
      signaling pathways downstream of TLR4. We have also shown that the double
      stranded RNA-binding protein kinase PKR is a component of both the TIRAP- and
      MyD88-dependent signaling pathways.

PMID- 11526400
TI  - Deletion of a coordinate regulator of type 2 cytokine expression in mice.
AB  - Mechanisms that underlie the patterning of cytokine expression in T helper (T(H))
      cell subsets remain incompletely defined. An evolutionarily conserved
      approximately 400-bp noncoding sequence in the intergenic region between the
      genes Il4 and Il13, designated conserved noncoding sequence 1 (CNS-1), was
      deleted in mice. The capacity to develop T(H)2 cells was compromised in vitro and
      in vivo in the absence of CNS-1. Despite the profound effect in T cells, mast
      cells from CNS-1(-/-) mice maintained their capacity to produce interleukin 4. A
      T cell-specific element critical for the optimal expression of type 2 cytokines
      may represent the evolution of a regulatory sequence exploited by adaptive
      immunity.

PMID- 11526401
TI  - Nonequivalent nuclear location of immunoglobulin alleles in B lymphocytes.
AB  - Individual B lymphocytes normally express immunoglobulin (Ig) proteins derived
      from single Ig heavy chain (H) and light chain (L) alleles. Allelic exclusion
      ensures monoallelic expression of Ig genes by each B cell to maintain single
      receptor specificity. Here we provide evidence that at later stages of B cell
      development, additional mechanisms may contribute to prioritizing expression of
      single IgH and IgL alleles. Fluorescent in situ hybridization analysis of primary
      splenic B cells isolated from normal and genetically manipulated mice showed that
      endogenous IgH, kappa and lambda alleles localized to different subnuclear
      environments after activation and had differential expression patterns. However,
      this differential recruitment and expression of Ig alleles was not typically seen
      among transformed B cell lines. These data raise the possibility that epigenetic
      factors help maintain the monoallelic expression of Ig.

PMID- 11526402
TI  - Lsc is required for marginal zone B cells, regulation of lymphocyte motility and
      immune responses.
AB  - Lsc (the murine homolog of human p115 Rho GEF) is a member of the Dbl-homology
      family of GTP exchange factors and is a specific activator of Rho. Lsc is
      activated by the G alpha(13) subunit of heterotrimeric G proteins and contains a
      regulator of G protein signaling domain that downmodulates G alpha(12) and G
      alpha(13). Lsc is expressed primarily in the hematopoietic system and links the
      activation of G alpha(12) and G alpha(13)-coupled receptors to actin
      polymerization in B and T cells. Lsc is essential for marginal zone B (MZB) cell
      homeostasis and for the generation of immune responses. Although Lsc-deficient
      lymphocytes show reduced basal motility, MZB cells show enhanced migration after
      serum activation. Thus, Lsc is a critical regulator of MZB cells and immune
      functions.

PMID- 11526403
TI  - Somatic activation of beta-catenin bypasses pre-TCR signaling and TCR selection
      in thymocyte development.
AB  - Mutation or ablation of T cell factor 1 and lymphocyte enhancer factor 1
      indicated involvement of the Wnt pathway in thymocyte development. The central
      effector of the Wnt pathway is beta-catenin, which undergoes stabilization upon
      binding of Wnt ligands to frizzled receptors. We report here that conditional
      stabilization of beta-catenin in immature thymocytes resulted in the generation
      of single positive T cells that lacked the alpha beta TCR and developed in the
      absence of pre-TCR signaling and TCR selection. Although active beta-catenin
      induced differentiation in the absence of TCRs, its action was associated with
      reduced proliferation and survival when compared to developmental changes induced
      by the pre-TCR or the alpha beta TCR.

PMID- 11526404
TI  - Proteolysis-independent regulation of PI3K by Cbl-b-mediated ubiquitination in T
      cells.
AB  - Cbl-b, a ring-type E3 ubiquitin protein ligase, is implicated in setting the
      threshold of T lymphocyte activation. The p85 regulatory subunit of
      phosphatidylinositol 3 kinase (PI3K) was identified as a substrate for Cbl-b. We
      have shown that Cbl-b negatively regulated p85 in a proteolysis-independent
      manner. Cbl-b is involved in the recruitment of p85 to CD28 and T cell antigen
      receptor zeta through its E3 ubiquitin ligase activity. The enhanced activation
      of Cbl-b(-/-) T cells was suppressed by the inhibition of PI3K. The results
      suggest a proteolysis-independent function for Cbl-b in the modification of
      protein recruitment.

PMID- 11526405
TI  - Separable effector T cell populations specialized for B cell help or tissue
      inflammation.
AB  - We identified specialized B helper and tissue inflammatory CD4(+) T cell subsets
      that developed concurrently from common naive precursors during the primary
      immune response. These separable populations were distinguishable by their
      expression of adhesion and chemoattractant receptors that directed their homing
      to the appropriate effector sites in vivo and also showed intrinsic differences
      in their ability to support B cell antibody production and produce effector
      cytokines in vitro. Thus, our data show a previously unappreciated functional
      specialization among CD4(+) effector T cells, further defining their diversity
      and role in adaptive immunity.

PMID- 11526406
TI  - Inducible IL-2 production by dendritic cells revealed by global gene expression
      analysis.
AB  - Dendritic cells (DCs) are strong activators of primary T cell responses. Their
      priming ability is acquired upon encounter with maturation stimuli. To identify
      the genes that are differentially expressed upon maturation induced by exposure
      to Gram-negative bacteria, a kinetic study of DC gene expression was done with
      microarrays representing 11,000 genes and ESTs (expressed sequence tags).
      Approximately 3000 differentially expressed transcripts were identified. We found
      that functional interleukin 2 (IL-2) mRNA, which gave rise to IL-2 production,
      was transiently up-regulated at early time-points after bacterial encounter. In
      contrast, macrophages did not produce IL-2 upon bacterial stimulation. Thus, IL-2
      is an additional key cytokine that confers unique T cell stimulatory capacity to
      DCs.

PMID- 11526408
TI  - The history of the stethoscope.

PMID- 11526409
TI  - Automated cardiac auscultation for detection of pathologic heart murmurs.
AB  - Experienced cardiologists can usually recognize pathologic heart murmurs with
      high sensitivity and specificity, although nonspecialists with less clinical
      experience may have more difficulty. Harsh, pansystolic murmurs of intensity
      grade > or = 3 at the left upper sternal border (LUSB) are likely to be
      associated with pathology. In this study, we designed a system for automatically
      detecting systolic murmurs due to a variety of conditions and examined the
      correlation between relative murmur intensity and likelihood of pathology.
      Cardiac auscultatory examinations of 194 children and young adults were recorded,
      digitized, and stored along with corresponding echocardiographic diagnoses, and
      automated spectral analysis using continuous wavelet transforms was performed.
      Patients without heart disease and either no murmur or an innocent murmur (n =
      95) were compared to patients with a variety of cardiac diagnoses and a
      pathologic systolic murmur present at the LUSB (n = 99). The sensitivity and
      specificity of the automated system for detecting pathologic murmurs with
      intensity grade > or = 2 were both 96%, and for grade > or = 3 murmurs they were
      100%. Automated cardiac auscultation and interpretation may be useful as a
      diagnostic aid to support clinical decision making.

PMID- 11526410
TI  - Long-distance transports of newborn infants with congenital heart disease.
AB  - Little has been published about specific problems that may occur during long
      distance transports of newborn cardiac patients. During a 4-year period after
      centralization of pediatric heart surgery in Sweden, 286 transports were
      prospectively investigated. A majority (77.3%) of the transports were carried out
      by nonspecialized teams. Ten severe adverse events, including the death of 1
      infant, occurred during the 286 transports (3.5%). Another infant died later of
      cerebral complications from hypoxia, rendering a transport-related mortality of
      0.7%. Twenty-two infants (7.7%) were severely hypoxic (oxygen saturation < or
      =65%) at arrival, and 12 of these infants suffered from transposition of the
      great arteries. During the second 2-year period increased use of intravenous
      prostaglandin E1 and transportation from tertiary-level units was associated with
      better transport outcome. During the same time period, overall 30-day
      postoperative mortality for pediatric cardiac surgery decreased from 4.0% to 1.2%
      in our hospital. When highly specialized treatment is centralized for quality
      reasons it is also important that risks associated with transport are considered
      and that the quality of transport is high. For some cardiac malformations
      antenatal diagnosis and referral of the mother for delivery to a center with
      pediatric cardiac surgery would probably further increase the chance of healthy
      survival in some infants.

PMID- 11526412
TI  - Congenital complete heart block in the fetus: hemodynamic features, antenatal
      treatment, and outcome in six cases.
AB  - Congenital heart block (CHB) can result in intrauterine cardiac failure leading
      to fetal or neonatal loss. To establish perinatal hemodynamic factors which might
      predict adverse outcome, six fetuses with CHB diagnosed between 20 and 30
      gestational weeks were examined by echocardiography at 2-week intervals. Neonatal
      morbidity and outcome in infancy are detailed. The fetuses showed a significant
      decrease in ventricular rate (VR) with advancing gestation (60 +/- 7 vs 51 +/- 4
      beats/min, p = 0.03). Cardiac decompensation defined as hydrops or pericardial
      effusion was associated with VR of lower than 55 beats/min in two fetuses. Three
      mothers had a therapeutic trial with a sympathomimetic and digoxin. Salbutamol
      increased VR 10% in one of three fetuses treated. Digoxin decreased pericardial
      effusion in one hydropic fetus with autoimmune myocarditis. In this fetus, poor
      left ventricular fractional shortening (LVFS) was accompanied with high umbilical
      artery resistance index (RI). High amniotic fluid erythropoietin indicated severe
      hypoxia preceding death. Pacemaker was indicated in all the newborns. At the age
      of 2 weeks all the surviving infants had tricuspid regurgitation and a shunt
      through foramen ovale due to asynchronized atrioventricular contraction. During
      the 12-month follow-up two of five surviving infants had no symptoms. One had
      symptomatic neonatal lupus. Two infants had patent ductus arteriosus, one with
      dilated cardiomyopathy. In conclusion, poor fetal outcome was associated with low
      VR, low LVFS, and high RI. Despite early pacing, morbidity was high in infancy
      due to cardiomyopathy and associated heart defects. Regular echocardiographic
      monitoring during pregnancy and after delivery is required in order to optimize
      care and timing of any interventions.

PMID- 11526413
TI  - Cardiac troponin I and N-terminal pro-brain natriuretic peptide in umbilical
      artery blood in relation to fetal heart rate abnormalities during labor.
AB  - The use of continuous fetal heart rate (FHR) recordings to monitor fetal well
      being during labor is standard clinical practice in developed countries. Little
      is known about the relationship, if any, that exists between these FHR
      abnormalities and the fetal cardiac musculature and function. The aim of this
      study was to investigate umbilical artery serum levels of cardiac troponin I, a
      sensitive and specific marker of myocardial necrosis, and N-terminal pro-brain
      natriuretic peptide (pro-BNP), a sensitive marker of left ventricular
      dysfunction, in relation to FHR abnormalities. Umbilical artery blood samples
      were taken from 27 cases immediately after delivery of the infant. There was
      evidence of significant FHR abnormalities in 11 of these cases (group 2) and the
      FHR recording was normal in 16 cases (group 1). The mean N-terminal pro-BNP level
      in umbilical artery serum in group 2 was 413 fmol/L (SEM = 85) and in group 1 was
      223 fmol/L (SEM = 28)(p = 0.022). There was no significant difference observed in
      cardiac troponin I levels between the two groups. Umbilical artery serum N
      terminal pro-BNP is elevated in association with fetal heart rate abnormality in
      the late stage of labor. This finding suggests that some degree of cardiac
      compromise accompanies FHR abnormality.

PMID- 11526414
TI  - Right atrial tunnel to the left atrial appendage: a danger during balloon
      septostomy.
AB  - Right atrial tunnel to the left atrial appendage is a very rare anomaly not
      previously described. Per se, it has no physiological significance but is a
      source of potential disaster during balloon atrial septostomy. The precise
      anatomy is demonstrated and ways are proposed to avoid tearing the atrial wall
      during therapeutic cardiac catheterization.

PMID- 11526415
TI  - Around PediHeart: noncompaction of the left ventricle.

PMID- 11526416
TI  - Reentrant tachycardia using two discrete atrioventricular nodes and a concealed
      atriofascicular pathway.
AB  - We describe a case of reentrant supraventricular tachycardia using two discrete
      atrioventricular (AV) nodes in the antegrade direction and a concealed
      atriofascicular pathway in the retrograde direction in a 21-year-old woman with
      superior-inferior ventricles and ventricular inversion. Using the Carto
      endocardial mapping system, two discrete AV nodes were identified as well as a
      separate decremental AV pathway located midway between the two nodes. Ablation of
      the separate pathway resulted in elimination of inducible tachycardia without
      loss of either AV node.

PMID- 11526417
TI  - Aneurysmal dilatation of the ductus arteriosus in a neonate.
AB  - Fetal ultrasound provides the capacity for early detection of a variety of
      congenital heart diseases. We report a case of aneurysmal dilatation of a patent
      ductus arteriosus detected in utero and subsequently confirmed by transthoracic
      echocardiography in the neonatal period. Prompt recognition of the ductus
      aneurysm with resultant surgical ligation may have averted potentially serious
      complications from this condition.

PMID- 11526418
TI  - Around PediHeart: bioprosthesis failure.

PMID- 11526419
TI  - An uncommon echocardiographic marker for anomalous origin of the left coronary
      artery from the pulmonary artery: visualization of intercoronary collaterals
      within the ventricular septum.
AB  - A rare and striking echocardiographic finding with color-flow Doppler-
      visualization of intercoronary collaterals within the ventricular septum--in an
      asymptomatic 5-year-old girl is reported. It strongly suggests anomalous origin
      of the left coronary artery from the pulmonary artery. Several additional
      echocardiographic features can secure the diagnosis and allow one to proceed with
      surgical correction without confirmatory cardiac catheterization and
      angiocardiography. The ages of our patient and of the seven cases reported
      previously suggest that these collaterals will more likely be identified beyond
      infancy and in relatively asymptomatic patients with this congenital anomaly.

PMID- 11526420
TI  - Ventricular aneurysm or diverticulum? Clinical differential diagnosis.
AB  - Intrathoracic ventricular aneurysms and diverticula can be differentiated by
      several criteria. Contractility is the only reliable parameter: aneurysms expand,
      whereas diverticula contract during ventricular systole.

PMID- 11526421
TI  - Surgical therapy of a coronary artery fistula draining into the left atrium.
AB  - Coronary artery fistulas (CAFs) are rare vascular anomalies. We describe a case
      of CAF draining into the left atrium, combined with an atrial septum defect (ASD)
      and azygos continuity in a 3-year-old girl. Surgical therapy included closure of
      the ASD combined with closure of the CAF through a left atrial approach. Even
      though CAF can be treated by interventional means, surgical correction may be
      required in the presence of associated cardiac abnormalities.

PMID- 11526422
TI  - Neurocardiogenic syncope in a 10-year-old boy.
AB  - We present a case with a suspected epileptic disorder. This may be a result of a
      neurocardiogenic syncope leading to seizures. A 10-year-old boy suffered two
      episodes of sudden loss of consciousness after getting injections.
      Electrocardiography (ECG) and electroencephalography recordings during a
      venipuncture showed asystole of 6 seconds followed by a generalized seizure with
      clonic jerks of the right arm and leg while theta waves in the EEG were noted.
      Tilt-table testing could not provoke a pathological reaction.

PMID- 11526423
TI  - Left atrial reduction and mitral valve replacement in a 5-year-old girl with
      severe mitral regurgitation and giant left atrium.
AB  - Giant left atrium associated with mitral valve disease has been implicated in the
      morbidity following mitral valve repair or replacement. Various methods including
      left atrial plication have been described to reduce the size of left atrium.
      Herein we describe our technique of left atrial reduction in a 5-year-old girl
      with severe mitral regurgitation and giant left atrium. She underwent mitral
      valve replacement and circumferential left atrial reduction with successful
      outcome.

PMID- 11526424
TI  - Antioxidants may mitigate the deterioration of coronary arteritis in patients
      with Kawasaki disease unresponsive to high-dose intravenous gamma-globulin.
AB  - During the early stages of Kawasaki disease, a marked increase in oxygen-free
      radicals (OFRs), which are produced by activated polymorphonuclear cells, may
      induce coronary arteritis. Early use of high-dose intravenous gamma-globulin
      (IVIG) and aspirin effectively blocked this deteriorating course of coronary
      arteritis; however, late use of IVIG, even using a high-dose schedule, did not
      achieve the same efficacy. The causes and reactions to the scenario of IVIG
      refractoriness have rarely been mentioned in the literature. We present an 11
      month-old male infant with Kawasaki disease and deteriorating coronary arteritis
      owing to late use of IVIG who showed dramatic responsiveness to the addition of
      alpha-tocopherol and ascorbic acid. We also discuss the possible mechanism.

PMID- 11526425
TI  - Percutaneous transluminal angioplasty of the left internal thoracic artery graft:
      a case report of a child operated on for anomalous origin of the left coronary
      artery from the pulmonary artery.
AB  - We report a case of an 8-year-old girl operated on with left internal thoracic
      artery-coronary artery anastomosis for anomalous left coronary artery from the
      pulmonary artery, in whom an early stenosis of the graft was successfully treated
      by percutaneous transluminal angioplasty.

PMID- 11526426
TI  - Around PediHeart: early bidirectional cavopulmonary anastomosis.

PMID- 11526427
TI  - Incidence and management of subaortic stenosis in Malta.

PMID- 11526429
TI  - Apaf1 is no longer single.

PMID- 11526430
TI  - Lipoxygenases and their involvement in programmed cell death.
AB  - Lipoxygenases are a family of enzymes which dioxygenate unsaturated fatty acids,
      thus initiating lipoperoxidation of membranes and the synthesis of signaling
      molecules. Consequently, they induce structural and metabolic changes in the cell
      in a number of pathophysiological conditions. Recently, a pro-apoptotic effect of
      lipoxygenase, and of the hydroperoxides produced thereof, has been reported in
      different cells and tissues, leading to cell death. Anti-apoptotic effects of
      lipoxygenases have also been reported; however, this has often been based on the
      use of enzyme inhibitors. Here we review the characteristics of the lipoxygenase
      family and its involvement in the initiation of oxidative stress-induced
      apoptosis. Finally, we discuss the role of lipoxygenase activation in apoptosis
      of animal and plant cells, suggesting a common signal transduction pathway in
      cell death conserved through evolution of both kingdoms.

PMID- 11526431
TI  - Transient expression of the Bcl-2 family member, A1-a, results in nuclear
      localization and resistance to staurosporine-induced apoptosis.
AB  - The Bcl-2 family of proteins has been characterized by either anti-apoptotic or
      pro-apoptotic activity. Insight into how Bcl-2 family members function has been
      gained by determining their intracellular localization. We have generated a
      monoclonal anti-A1-a antibody and used a COS-7 overexpression system to study the
      localization of the murine anti-apoptotic Bcl-2 family member, A1-a. A1-a
      overexpressed in COS-7 cells localized to the nucleus as determined by
      subcellular fractionation and immunofluorescent microscopy. A1-a in the COS-7
      nucleus bound tightly to the nuclear matrix as evidenced by resistance to
      treatment with DNAse I and RNAse A and sequential extraction with 1.0% Triton X
      100, 0.15 M NaCl, 0.25 M HCl, 0.5 M Tris pH 7.4 and 6 M urea. HPLC analysis of A1
      a, subsequent to SDS extraction, produced fractions that gave multiple bands when
      analyzed by Western blot analysis suggesting a propensity to form multimers. COS
      7 cells transfected with A1-a were protected from apoptotic induction by
      staurosporine treatment.

PMID- 11526432
TI  - Mitochondrial targeting of JNK/SAPK in the phorbol ester response of myeloid
      leukemia cells.
AB  - Treatment of human U-937 myeloid leukemia cells with 12-O-tetradecanoylphorbol-13
      acetate (TPA) is associated with activation of the stress-activated protein
      kinase (SAPK) and induction of terminal monocytic differentiation. The present
      studies demonstrate that TPA targets SAPK to mitochondria by a mechanism
      dependent on activation of protein kinase C (PKC) beta. Translocation of SAPK to
      mitochondria in response to TPA is associated with release of cytochrome c,
      caspase-3 activation and induction of apoptosis. The results show that TPA
      induces the association of SAPK with the mitochondrial anti-apoptotic Bcl-x(L)
      protein. Overexpression of Bcl-x(L) attenuated the apoptotic response to TPA
      treatment. Moreover, expression of Bcl-x(L) mutated at sites of SAPK
      phosphorylation (Thr-47, -115) was more effective than wild-type Bcl-x(L) in
      abrogating TPA-induced cytochrome c release and apoptosis. By contrast,
      expression of Bcl-x(L) had little effect on induction of the monocytic phenotype.
      These findings indicate that myeloid leukemia cells respond to TPA with targeting
      of SAPK to mitochondria and that this response contributes to terminal
      differentiation through the release of cytochrome c and induction of apoptosis.

PMID- 11526433
TI  - Increased expression and activation of poly(ADP-ribose) polymerase (PARP)
      contribute to retinal ganglion cell death following rat optic nerve transection.
AB  - Excessive activation of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) by
      free-radical damaged DNA mediates necrotic cell death in injury models of
      cerebral ischemia-reperfusion and excitotoxicity. We recently reported that
      secondary retinal ganglion cell (RGC) death following rat optic nerve (ON)
      transection is mainly apoptotic and can significantly but not entirely be blocked
      by caspase inhibition. In the present study, we demonstrate transient, RGC
      specific PARP activation and increased retinal PARP expression early after ON
      axotomy. In addition, intravitreal injections of 3-aminobenzamide blocked PARP
      activation in RGCs and resulted in an increased number of surviving RGCs when
      compared to control animals 14 days after ON transection. These data indicate
      that secondary degeneration of a subset of axotomized RGCs results from a
      necrotic-type cell death mediated by PARP activation and increased PARP
      expression. Furthermore, PARP inhibition may constitute a relevant strategy for
      clinical treatment of traumatic brain injury.

PMID- 11526434
TI  - Escherichia coli induces apoptosis and proliferation of mammary cells.
AB  - Mammary cell apoptosis and proliferation were assessed after injection of
      Escherichia coli into the left mammary quarters of six cows. Bacteriological
      analysis of foremilk samples revealed coliform infection in the injected quarters
      of four cows. Milk somatic cell counts increased in these quarters and peaked at
      24 h after bacterial injection. Body temperature also increased, peaking at 12 h
      postinjection. The number of apoptotic cells was significantly higher in the
      mastitic tissue than in the uninfected control. Expression of Bax and interleukin
      1beta converting enzyme increased in the mastitic tissue at 24 h and 72 h
      postinfection, whereas Bcl-2 expression decreased at 24 h but did not differ
      significantly from the control at 72 h postinfection. Induction of matrix
      metalloproteinase-9, stromelysin-1 and urokinase-type plasminogen activator was
      also observed in the mastitic tissue. Moreover, cell proliferation increased in
      the infected tissue. These results demonstrate that Escherichia coli-induced
      mastitis promotes apoptosis and cell proliferation.

PMID- 11526435
TI  - Poly (ADP-ribose) polymerase inhibitor increases apoptosis and reduces necrosis
      induced by a DNA minor groove binding methyl sulfonate ester.
AB  - The poly(ADP-ribose) polymerase (PARP) is involved in cell recovery from DNA
      damage, such as methylation of N3-adenine, that activates the base excision
      repair process. In the present study we demonstrated that MeOSO(2)(CH(2))(2)
      lexitropsin (Me-Lex), a methylating agent that almost exclusively produces N3
      methyladenine, induced different modalities of cell death in human leukemic cell
      lines, depending on the presence of PARP inhibitor. Growth inhibition, provoked
      by the combination of Me-Lex and PARP inhibitor, was associated with a marked
      down-regulation of c-myc, increased generation of single strand breaks and
      apoptosis. When used as single agent, at concentrations that saturated cell
      repair ability, Me-Lex induced mainly cell death by necrosis. Surprisingly,
      addition of a PARP inhibitor enhanced apoptosis and reduced the early appearance
      of necrosis. Telomerase activity was completely suppressed in cells exposed to Me
      Lex alone, by 24 h after treatment, whereas it did not change when Me-Lex was
      combined with PARP inhibitor. Thereafter, inhibition of telomerase was observed
      with both treatments. The results suggest new insights on different modalities of
      cell death induced by high levels of N3-methyladenine per se, or by the
      methylated base in the presence of PARP inhibitor.

PMID- 11526436
TI  - Death receptor-induced apoptotic and necrotic cell death: differential role of
      caspases and mitochondria.
AB  - In L929sAhFas cells, tumor necrosis factor (TNF) leads to necrotic cell death,
      whereas agonistic anti-Fas antibodies elicit apoptotic cell death. Apoptosis, but
      not necrosis, is correlated with a rapid externalization of phosphatidylserine
      and the appearance of a hypoploid population. During necrosis no cytosolic and
      organelle-associated active caspase-3 and -7 fragments are detectable. The
      necrotic process does not involve proteolytic generation of truncated Bid;
      moreover, no mitochondrial release of cytochrome c is observed. Bcl-2
      overexpression slows down the onset of necrotic cell death. In the case of
      apoptosis, active caspases are released to the culture supernatant, coinciding
      with the release of lactate dehydrogenase. Following necrosis, mainly unprocessed
      forms of caspases are released. Both TNF-induced necrosis and necrosis induced by
      anti-Fas in the presence of the caspase inhibitor benzyloxycarbonyl-Val-Ala
      Asp(OMe)-fluoromethylketone are prevented by the serine protease inhibitor N
      tosyl-L-phenylalanine chloromethylketone and the oxygen radical scavenger
      butylated hydroxyanisole, while Fas-induced apoptosis is not affected.

PMID- 11526437
TI  - Staurosporine inhibits phosphorylation of translational regulators linked to
      mTOR.
AB  - Treatment of Swiss 3T3 cells with staurosporine resulted in dephosphorylation of
      two proteins which play key roles in regulating mRNA translation. This occurred
      before the execution of apoptosis, assessed by caspase-3 activity. These
      translation regulators are p70 S6 kinase, which phosphorylates ribosomal protein
      S6, and eukaryotic initiation factor (eIF) 4E binding protein 1 (4E-BP1), which
      both lie downstream of the mammalian target of rapamycin (mTOR). This resulted in
      decreased p70 S6 kinase activity, dephosphorylation of ribosomal protein S6,
      increased binding of 4E-BP1 to eIF4E and a concomitant decrease in eIF4F
      complexes. Our data show that staurosporine impairs mTOR signalling in vivo but
      that this not due to direct inhibition of mTOR or to inhibition of protein kinase
      C. It is becoming clear that agents which cause apoptosis inactivate mTOR
      signalling as a common early response prior to the execution of apoptosis, i.e.,
      before caspase activation.

PMID- 11526438
TI  - Glycine blocks opening of a death channel in cultured hepatic sinusoidal
      endothelial cells during chemical hypoxia.
AB  - Using confocal microscopy, we investigated mechanisms underlying loss of plasma
      membrane integrity during necrotic death of cultured hepatic sinusoidal
      endothelial cells exposed to 2.5 mM potassium cyanide (chemical hypoxia). After 2
      3 h, the anionic fluorophore calcein abruptly began to enter the cytosol, and
      nuclei labeled with cationic propidium after another 2-5 min. As calcein
      permeated, growth of blebs on the plasma membrane accelerated. Lucifer yellow,
      another anionic fluorophore, entered identically to calcein, whereas high
      molecular weight dextrans (40-2000 kDa) entered like propidium. Glycine slowed,
      but did not prevent calcein entry, whereas permeation of propidium and high
      molecular weight dextrans was blocked completely by glycine. These findings
      suggest that opening of a glycine-sensitive organic anion channel, or death
      channel, precipitates a metastable state characterized by rapid cell swelling and
      bleb growth. This metastable state culminates in non-specific breakdown of the
      plasma membrane permeability barrier and irreversible cell death.

PMID- 11526439
TI  - AP-1 mediated retinal photoreceptor apoptosis is independent of N-terminal
      phosphorylation of c-Jun.
AB  - Apoptosis is essential for retinal development but it is also a major mode of
      cell loss in many human retinal dystrophies. High levels of visible light induce
      retinal apoptosis in mice and rats. This process is dependent on the induction of
      the transcription factor AP-1, a dimeric complex composed of c-Fos and c-Jun/JunD
      phosphoproteins. While c-Fos is essential, JunD is dispensable for light-induced
      photoreceptor apoptosis. Here we show that N-terminal phosphorylation of c-Jun,
      the other main partner of c-Fos in induced AP-1 complexes is not required for
      programmed cell death during retinal development in vivo and is also dispensable
      for photoreceptor apoptosis induced by the exogenous stimuli "excessive light"
      and N-nitroso-N-methylurea (MNU). Mice expressing a mutant c-Jun protein (JunAA)
      that cannot be phosphorylated at its N-terminus are apoptosis competent and their
      retina is not distinguishable from wild-type mice. Accordingly, Jun kinase,
      responsible for phosphorylation of wild-type c-Jun protein is at best only
      marginally induced by the apoptotic stimuli "light" and MNU. Complex composition
      of light-induced AP-1 complexes is similar in wild-type and JunAA mice. This
      shows that the mutant c-Jun protein can be part of the DNA binding complex AP-1
      and demonstrates that induction of the DNA binding activity of AP-1 after light
      insult does not depend on N-terminal phosphorylation of c-Jun. Our results
      suggest that transactivation of target genes by phosphorylated c-jun/AP-1 is not
      required for MNU- or light-induced apoptosis of photoreceptor cells.

PMID- 11526441
TI  - Isolation of neuronal cells with high processing activity for the Machado-Joseph
      disease protein.

PMID- 11526442
TI  - Conformational change of Bax: a question of life or death.

PMID- 11526440
TI  - Caspase-14, a keratinocyte specific caspase: mRNA splice variants and expression
      pattern in embryonic and adult mouse.

PMID- 11526443
TI  - Retinoic acid receptor-independent mechanism of apoptosis of melanoma cells by
      the retinoid CD437 (AHPN).
AB  - Retinoic acid (RA) induces differentiation of S91 melanoma cells through
      activation of RA receptor (RAR)gamma without affecting cell viability. The novel
      RARgamma-agonist CD437 (AHPN), however, also induces concomitant apoptosis
      through an unknown mechanism which was investigated here. By utilizing DNA
      microarray analysis, five apoptosis-associated, CD437-induced transcripts (CITs)
      were identified. Interestingly, all CITs are also regulated by p53 in a DNA
      damage response, and consistent with this interpretation, CD437 was found to
      cause DNA adduct-formation. However, p53 is not required for CD437-dependent
      regulation of CITs. Among this set of genes, induction of p21(WAF1/CIP1) is
      likely to be responsible for early S-phase growth-arrest of CD437-treated cells,
      whereas ei24 is a critical mediator of CD437-induced apoptosis in S91 cells.
      These data suggest an RAR-independent mechanism in which CD437 causes DNA adduct
      formation, resulting in induction of a p53-independent DNA damage response, and
      subsequent growth-arrest and apoptosis. CD437-mediated DNA adduct-formation may
      also explain its apoptotic effects in other cell types.

PMID- 11526444
TI  - Sponge Bcl-2 homologous protein (BHP2-GC) confers distinct stress resistance to
      human HEK-293 cells.
AB  - It is established that sponges, the phylogenetically oldest still extant phylum
      of Metazoa, possess key molecules of the apoptotic pathways, that is members from
      the Bcl-2 family and a pro-apoptotic molecule with death domains. Here we report
      on transfection studies of human cells with a sponge gene, GCBHP2. Sponge tissue
      was exposed to heat shock and tributyltin, which caused an upregulation of gene
      expression of GCBHP2. The cDNA GCBHP2 was introduced into human HEK-293 cells and
      mouse NIH-3T3 cells; the stable transfection was confirmed by the identification
      of the transcripts, by Western blotting as well as by immunofluorescence using
      antibodies raised against the recombinant polypeptide. HEK-293 cells, transfected
      with GCBHP2, showed high resistance to serum starvation and tributyltin
      treatment, compared to mock-transfected cells. In contrast to mock-transfected
      cells, GCBHP2-transfected cells activated caspase-3 to a lower extent. Thus,
      sponges contain gene(s) involved in apoptotic pathway(s) displaying their
      function also in human cells.

PMID- 11526445
TI  - Involvement of protein kinase C-delta in DNA damage-induced apoptosis.
AB  - We have previously shown that the protein kinase C (PKC) signal transduction
      pathway regulates cell death by the DNA damaging agent cis
      diamminedichloroplatinum(II) (cDDP). In the present study we have investigated
      how PKC influences the sequence of events that are triggered by cDDP-induced DNA
      damage. cDDP caused activation of caspases-8, -9, -3, -7 and cleavage of
      PKCdelta. Rottlerin, a selective inhibitor of novel PKCdelta, blocked activation
      of caspases, proteolytic activation of PKCdelta and cell death induced by cDDP.
      In contrast, Go 6976, an inhibitor of conventional PKCalpha and betaI, did not
      prevent cDDP-induced caspase activation and cDDP cytotoxicity. In HeLa cells,
      PKCdelta was distributed both in the cytosol and heavy membrane (HM) fraction
      containing mitochondria. While caspase-8 was primarily cytosolic, a small amount
      of caspases-9, -7 and -3 could be detected in the HM fraction. cDDP caused a time
      dependent increase in Cytochrome c release from the mitochondria and processing
      of both cytosolic and membrane-associated caspases, as well as proteolytic
      cleavage of PKCdelta. Rottlerin attenuated late but not early release of
      Cytochrome c by cDDP. It, however, inhibited activation of caspases and
      proteolytic cleavage of PKCdelta in both cytosolic and HM fractions. The
      antiapoptotic effect of rottlerin was evident when it was added together with or
      following cDDP addition but not when added after cDDP was removed from the
      medium. Thus, the PKCdelta inhibitor acts at an early stage of the cDDP-induced
      cell death pathway that precedes caspase activation.

PMID- 11526446
TI  - Bax translocation to mitochondria subsequent to a rapid loss of mitochondrial
      membrane potential.
AB  - Bax, a pro-apoptotic member of the Bcl-2 family, is a cytosolic protein that
      inserts into mitochondrial membranes upon induction of cell death. Using the
      green fluorescent protein fused to Bax (GFP-Bax) to quantitate mitochondrial
      binding in living cells we have investigated the cause of Bax association with
      mitochondria and the time course relative to endogenous and induced changes in
      mitochondrial membrane potential (DeltaPsi(m)). We have found that staurosporine
      (STS) induces a loss in DeltaPsi(m) before GFP-Bax translocation can be measured.
      The onset of the DeltaPsi(m) loss is followed by a rapid and complete collapse of
      DeltaPsi(m) which is followed by Bax association with mitochondria. The
      mitochondria uncoupler FCCP, in the presence of the F(1)-F(0) ATPase inhibitor
      oligomycin, can trigger Bax translocation to mitochondria suggesting that when
      ATP levels are maintained a collapse of DeltaPsi(m) induces Bax translocation.
      Neither FCCP nor oligomycin alone alters Bax location. Bax association with
      mitochondria is also triggered by inhibitors of the electron transport chain,
      antimycin and rotenone, compounds that collapse DeltaPsi(m) without inducing
      rapid ATP hydrolysis that typically occurs with uncouplers such as FCCP. Taken
      together, our results suggest that alterations in mitochondrial energization
      associated with apoptosis can initiate Bax docking to mitochondria.

PMID- 11526447
TI  - Poly(ADP-ribose) polymerase inhibitors attenuate necrotic but not apoptotic
      neuronal death in experimental models of cerebral ischemia.
AB  - An excessive activation of poly(ADP-ribose) polymerase (PARP) has been proposed
      to play a key role in post-ischemic neuronal death. We examined the
      neuroprotective effects of the PARP inhibitors benzamide, 6(5H)-phenanthridinone,
      and 3,4-dihydro-5-[4-1(1-piperidinyl)buthoxy]-1(2H)-isoquinolinone in three
      rodent models of cerebral ischemia. Increasing concentrations of the three PARP
      inhibitors attenuated neuronal injury induced by 60 min oxygen-glucose
      deprivation (OGD) in mixed cortical cell cultures, but were unable to reduce CA1
      pyramidal cell loss in organotypic hippocampal slices exposed to 30 min OGD or in
      gerbils following 5 min bilateral carotid occlusion. We then examined the
      necrotic and apoptotic features of OGD-induced neurodegeneration in cortical
      cells and hippocampal slices using biochemical and morphological approaches.
      Cortical cells exposed to OGD released lactate dehydrogenase into the medium and
      displayed ultrastructural features of necrotic cell death, whereas no caspase-3
      activation nor morphological characteristics of apoptosis were observed at any
      time point after OGD. In contrast, a marked increase in caspase-3 activity was
      observed in organotypic hippocampal slices after OGD, together with fluorescence
      and electron microscope evidence of apoptotic neuronal death in the CA1
      subregion. Moreover, the caspase inhibitor Z-VAD-FMK reduced OGD-induced CA1
      pyramidal cell loss. These findings suggest that PARP overactivation may be an
      important mechanism leading to post-ischemic neurodegeneration of the necrotic
      but not of the apoptotic type.

PMID- 11526448
TI  - Bcl-x(S) can form homodimers and heterodimers and its apoptotic activity requires
      localization of Bcl-x(S) to the mitochondria and its BH3 and loop domains.
AB  - Proteins of the Bcl-2 family regulate apoptosis, some antagonizing cell death and
      others, such as Bcl-x(S), promoting it. We previously showed that expression of
      Bcl-x(S) in PC12 cells is a useful system for studying the mechanism of Bcl-x(S)
      induced apoptosis. To further investigate this apoptotic effect and its
      prevention by anti-apoptotic agents, we assessed the role of distinct Bcl-x(S)
      domains, via the study of their mutations, on the ability of Bcl-x(S) to induce
      apoptosis and to localize to the mitochondria, as well as the ability of these
      domains to counteract the effects of anti-apoptotic agents on Bcl-x(S). Deletion
      of the transmembrane domain (DeltaTM) prevented the localization of Bcl-x(S)
      DeltaTM to the mitochondria and the ability of this mutant to induce apoptosis.
      Deletion of the amino acids GD 94-95 from the BH3 domain, or deletion of the loop
      region, impaired the ability of these mutants to induce apoptosis but not their
      localization to the mitochondria. Deletion of the BH4 domain or destruction of
      the caspase cleavage site in the loop region (by replacing amino acid D61 with
      A61) did not affect either the localization of these mutants to the mitochondria
      or their ability to induce cell death. It thus appears that Bcl-x(S)-induced
      apoptosis in PC12 cells is mediated by localization of Bcl-x(S) to the
      mitochondria by a process that requires the transmembrane domain. Furthermore,
      once localized to the mitochondria Bcl-x(S) requires the BH3 domain, and to a
      lesser extent the loop domain, for its subsequent activity. The anti-apoptotic
      agents Bcl-2 and Bcl-x(L), the caspase inhibitor Z-VAD-FMK, and nerve growth
      factor (NGF) did not prevent Bcl-x(S) localization to the mitochondria, and did
      not require the BH4 or the loop domains of Bcl-x(S) for their survival effect.
      Bcl-x(S) is capable of forming homodimers with itself and heterodimers with Bcl
      x(L) or Bcl-2. Accordingly co-expression of Bcl-x(S) DeltaTM with Bcl-x(S), Bcl
      2, or Bcl-x(L) leads to a change in the subcellular distribution of Bcl-x(S)
      DeltaTM, from a diffuse distribution throughout the cell to a more defined
      distribution. Moreover co-immunoprecipitation experiments directly demonstrated
      that Bcl-x(S) can associate with GFP-Bcl-x(S), Bcl-x(L), or Bcl-2. These results
      suggest that such Bcl-x(S) interactions may be important for the mechanism of
      action of this protein.

PMID- 11526449
TI  - Opioids are non-competitive inhibitors of nitric oxide synthase in T47D human
      breast cancer cells.
AB  - Opioids and nitric oxide (NO) interact functionally in different systems. NO
      generating agents decrease the activity of opioid agonists, prevent opioid
      tolerance, and are used in opioid withdrawal syndromes. There exist, however, few
      reports indicating a direct interaction of the two systems. T47D human breast
      cancer cells in culture express opioid receptors, and opioid agonists inhibit
      their growth, while they release high amounts of the NO-related molecules NO(2
      )/NO(3-)to the culture medium. We have used this system to assay a possible
      direct interaction of opiergic and nitric oxide systems. Our results show that
      delta- or mu-acting opioid agonists do not modify the release of NO(2-)/NO(3-).
      In contrast, kappa-acting opioid agonists (ethylketocyclazocine, and alpha(S1)
      casomorphine) decrease the release of NO(2-)/NO(3-), in a time- and dose
      dependent manner. The general opioid antagonist diprenorphine (10(-6) M) produce
      a similar NO(2-)/NO(3-)release inhibition, indicating a possible non-opioid
      receptor mediated phenomenon. In addition, ethylketocyclazocine, alpha(S1)
      casomorphin and diprenorphine directly inhibit NOS activity: agonists, interact
      with both calcium-dependent and independent NOS-isoforms, while the antagonist
      diprenorphine modifies only the activity of the calcium-dependent fraction of the
      enzyme. Analysis of this interaction revealed that opioids modify the dimeric
      active form of NOS, through binding to the reductase part of the molecule, acting
      as non-competitive inhibitors of the enzyme. This interaction opens interesting
      new possibilities for tumor biology and breast cancer therapy.

PMID- 11526450
TI  - Thymocytes selected for resistance to hydrogen peroxide show altered antioxidant
      enzyme profiles and resistance to dexamethasone-induced apoptosis.
AB  - Treatment of WEHI7.2 cells, a mouse thymoma-derived cell line, with
      dexamethasone, a synthetic glucocorticoid, causes the cells to undergo apoptosis.
      Previous work has shown that treatment of WEHI7.2 cells with dexamethasone
      results in a downregulation of antioxidant defense enzymes, suggesting that
      increased oxidative stress may play a role in glucocorticoid-induced apoptosis.
      To test whether resistance to oxidative stress causes resistance to dexamethasone
      induced apoptosis, WEHI7.2 cell variants selected for resistance to 50, 100 and
      200 microM H(2)O(2) were developed. Resistance to H(2)O(2) is accompanied by
      increased antioxidant enzyme activity, resistance to other oxidants and a delayed
      loss of viable cells after dexamethasone treatment. In the 200 microM H(2)O(2)
      resistant cell variant the delay in cell loss is correlated with delayed release
      of cytochrome c from the mitochondria into the cytosol. This suggests that
      reactive oxygen species play a role in a signaling event during steroid-mediated
      apoptosis in lymphocytes.

PMID- 11526452
TI  - Mapping of herpes simplex virus-1 VP22 functional domains for inter- and
      subcellular protein targeting.
AB  - The herpes simplex virus 1 (HSV-1) tegument protein VP22 has been utilised as a
      vehicle for trafficking proteins. It has a remarkable property of exiting the
      cell that is producing it and entering the neighbouring cells, which has been
      used to deliver therapeutic proteins, p53 and herpes simplex virus thymidine
      kinase (tk). It has a complex pattern of expression and subcellular localisation.
      Functions of VP22 include intercellular transport, binding to and bundling of
      microfilaments, inducing cytoskeleton collapse, nuclear translocation during
      mitosis, and binding to chromatin and nuclear membrane. The regions of VP22 which
      contain each of these functions have not been characterised. Finding the region
      carrying the property of intercellular spread would facilitate enhancement of
      transport function. By constructing a series of deletion constructs of VP22
      tagged by the green fluorescent protein (GFP) we have mapped the functions of
      VP22 to specific regions in the polypeptide as follows: intercellular transport -
      aa 81-195; binding and reorganisation of cytoskeleton - aa 159-267; nuclear
      targeting, inhibition of cytoskeleton collapse - aa 81-121; and nuclear targeting
      and facilitation of intercellular transport - aa 267-301. Separation of VP22
      functions enables focus on the mechanism of VP22-mediated transport and improve
      the transportation efficiency of VP22.

PMID- 11526451
TI  - Skeletal muscle regeneration after insulin-like growth factor I gene transfer by
      recombinant Sendai virus vector.
AB  - We scrutinized the applicability and efficacy of Sendai virus (SeV) vectors
      expressing either LacZ or human insulin-like growth factor-I (hIGF-I) in gene
      transfer into skeletal muscle. Seven days after the intramuscular injection of
      LacZ/SeV X-gal labeled myofibers were demonstrated in rat anterior tibialis
      muscle with/without bupivacaine treatment and the transgene expression persisted
      up to 1 month after injection. Recombinant hIGF-I was detected as a major protein
      species in culture supernatants of a neonatal rat myoblast cell line L6 and thus
      induced the cells to undergo myogenetic differentiation. The introduction of hIGF
      I/SeV into the muscle showed a significant increase in regenerating and split
      myofibers which were indicative of hypertrophy, and also an increase in the total
      number of myofibers, in comparison to that seen in the LacZ/SeV-treated control
      muscle. These results demonstrate that SeV achieves high-level transgene
      expression in skeletal muscle, and that hIGF-I gene transfer using SeV vector may
      therefore have great potential in the treatment of neuromuscular disorders.

PMID- 11526453
TI  - Latency associated promoter transgene expression in the central nervous system
      after stereotaxic delivery of replication-defective HSV-1-based vectors.
AB  - The herpes simplex virus type 1 (HSV-1) latency associated promoter (LAP) has
      been shown to sustain long-term reporter gene expression within sensory neurones.
      Its activity within the CNS is, however, less well understood. In this study we
      characterise the activity of the LAP after stereotaxic delivery of recombinant
      HSV-1-based vectors to the brain. Two classes of vectors were utilised in these
      studies: (1) a replication-defective vector lacking the glycoprotein H and
      thymidine kinase genes, designated CS1, and (2) a virus mutant severely impaired
      for immediate-early (IE) gene expression which lacks functional VP16, ICP4 and
      ICP0 genes, designated in1388. Both vectors contain the LacZ gene under the
      control of the LAP. Following delivery of either vector to the striatum, beta-gal
      expression was detected within anatomically related CNS regions distal to the
      site of injection. At these sites the number of beta-gal-positive cells increased
      with time and remained stable up to 4 weeks p.i. beta-Gal expression could not be
      detected at the site of injection after delivery of CS1 but beta-gal expression
      within neurones located at this site was observed after delivery of in1388,
      indicating reduced toxicity of this severely disabled virus. Transgene expression
      decreased dramatically with both vectors at later time-points (>4 weeks after
      delivery), but PCR analysis demonstrated that viral genomes were stably
      maintained for up to 180 days following delivery, indicating that the loss of
      beta-gal-positive neurones was not likely to be due to a loss of vector
      transduced cells. Moreover, after delivery of an equivalent virus to the rat
      striatum in situ hybridisation analysis showed a similar decrease in the number
      of neurones expressing the endogenous LATs with time. These data indicate that
      although the HSV-1 LAP can drive the expression of foreign genes in a variety of
      CNS neurones, in these cells there is a slow down-regulation of the viral
      promoter which eventually results in the loss of detectable transgene expression.

PMID- 11526454
TI  - Direct correlation between positron emission tomographic images of two reporter
      genes delivered by two distinct adenoviral vectors.
AB  - Biodistribution, magnitude and duration of a therapeutic transgene's expression
      may be assessed by linking it to the expression of a positron emission tomography
      (PET) reporter gene (PRG) and then imaging the PRG's expression by a PET reporter
      probe (PRP) in living animals. We validate the simple approach of co
      administering two distinct but otherwise identical adenoviruses, one expressing a
      therapeutic transgene and the other expressing the PRG, to track the therapeutic
      gene's expression. Two PET reporter genes, a mutant herpes simplex virus type 1
      thymidine kinase (HSV1-sr39tk) and dopamine-2 receptor (D(2)R), each regulated by
      the same cytomegalovirus (CMV) promoter, have been inserted into separate
      adenoviral vectors (Ad). We demonstrate that cells co-infected with equivalent
      titers of Ad-CMV-HSV1-sr39tk and Ad-CMV-D(2)R express both reporter genes with
      good correlation (r(2) = 0.93). Similarly, a high correlation (r(2) = 0.97) was
      observed between the expression of both PRGs in the livers of mice co-infected
      via tail-vein injection with equivalent titers of these two adenoviruses.
      Finally, microPET imaging of HSV1-sr39tk and D(2)R expression with 9-(4
      [(18)F]fluoro-3-hydroxymethylbutyl) guanine ([(18)F]FHBG) and 3-(2
      [(18)F]fluoroethyl)spiperone ([(18)F]FESP), utilizing several adenovirus-mediated
      delivery routes, illustrates the feasibility of evaluating relative levels of
      transgene expression in living animals, using this approach.

PMID- 11526455
TI  - Intraventricular administration of recombinant adenovirus to neonatal twitcher
      mouse leads to clinicopathological improvements.
AB  - Twitcher mouse is a murine model of human globoid cell leukodystrophy (Krabbe
      disease), which is characterized by a genetic deficiency in galactocerebrosidase
      (GALC) activity. The nervous system is affected early and severely by
      demyelination in the white matter. So far, there is no effective treatment for
      Krabbe disease except bone marrow transplantation (BMT). However, BMT has
      inherent limitations such as unavailability of donors and graft-versus-host
      disease. In this study, we injected recombinant adenovirus encoding GALC into the
      lateral ventricle of twitcher mice at postnatal day 0 (PND 0) and the therapeutic
      effects were evaluated. Our results showed slight, but significant improvements
      in motor functions, body weight and twitching and a prolonged life span. In
      brain, GALC activity was increased to 15% that of normal littermates and
      psychosine concentration was decreased to 55% that of untreated twitcher mice at
      PND 15. The number of PAS-positive globoid cells in brain stem was also reduced
      significantly at PND 35. In contrast, when adenoviruses were injected to the
      twitcher mice at PND 15, almost no improvements were observed. These results
      demonstrate that the timing of treatment may be of great importance in Krabbe
      disease.

PMID- 11526456
TI  - Evidence for nonspecific adsorption of targeted retrovirus vector particles to
      cells.
AB  - The ability to specifically target a cell-type is important for the development
      of vectors for in vivo gene therapy. In order to produce retrovirus vectors
      targeting ovarian cancer cells, which specifically overexpress alpha folate
      receptor (alphaFR), a single chain antibody was fused as an N-terminal extension
      of the ecotropic and amphotropic murine leukemia virus (MLV) envelope
      glycoproteins. Vector particles bearing the modified glycoproteins were produced
      and analysed. Although conventional FACS studies indicated that viral particles
      bearing the modified Env could bind to ovarian cancer cells, targeted infection
      was not achieved. The initial step of virus-cell interaction was further studied
      using an immunofluorescence technique, which allows visualisation of single
      retrovirus particles. Vectors bearing chimeric or wild-type glycoproteins bound
      equally well to cells with or without the targeted receptor, although soluble
      chimeric glycoproteins bound specifically to FBP. Our results indicate that the
      incorporation of specific ligands to the virus envelope does not necessarily
      result in significant enhancement of vector particle binding. A similar
      interaction was also observed using Env-defective virus particles, suggesting
      that cellular factors incorporated into the lipid envelope play a dominant role
      in promoting initial adsorption of virus particles to cells. Significant
      implications arise from these observations on the interpretation of previous
      reports on 'targeted' vectors, and for the development of vectors for in vivo
      gene therapy protocols.

PMID- 11526457
TI  - Electrotransfer of naked DNA in the skeletal muscles of animal models of muscular
      dystrophies.
AB  - The electrotransfer of naked DNA has recently been adapted to the transduction of
      skeletal muscle fibers. We investigated the short- and long-term efficacy of this
      methodology in wild-type animals and in mouse models of congenital muscular
      dystrophy (dy/dy, dy(2J)/dy(2J)), or Duchenne muscular dystrophy (mdx/mdx). Using
      a reporter construct, the short-term efficacy of fiber transduction reached 40%
      and was similar in wild-type, dy/dy and dy(2J)/dy(2J) animals, indicating that
      ongoing muscle fibrosis was not a major obstacle to the electrotransfer-mediated
      gene transfer. Although the complete rejection of transduced fibers was observed
      within 3 weeks in the absence of immunosuppression, the persistency was prolonged
      over 10 weeks when transient or continuous immunosuppressive regimens were used.
      Using therapeutic plasmids, we demonstrated that electrotransfer also allowed the
      transduction of large constructs encoding the laminin alpha2 chain in dy/dy
      mouse, or a chimeric dystrophin-EGFP protein in mdx/mdx mouse. The correct
      sarcolemmal localization of these structural proteins demonstrated the functional
      relevance of their expression in vivo, with a diffusion domain estimated to be
      300 to 500 microm. However, degeneration-regeneration events hampered the long
      term stability of transduced fibers. Given its efficacy for naked DNA transfer in
      these models of muscular dystrophies, and despite some limitations, gene
      electrotransfer methodology should be further explored as a potential avenue for
      treatment of muscular dystrophies.

PMID- 11526458
TI  - Chitosan as a nonviral gene delivery system. Structure-property relationships and
      characteristics compared with polyethylenimine in vitro and after lung
      administration in vivo.
AB  - Chitosan is a natural cationic linear polymer that has recently emerged as an
      alternative nonviral gene delivery system. We have established the relationships
      between the structure and the properties of chitosan-pDNA polyplexes in vitro.
      Further, we have compared polyplexes of ultrapure chitosan (UPC) of preferred
      molecular structure with those of optimised polyethylenimine (PEI) polyplexes in
      vitro and after intratracheal administration to mice in vivo. Chitosans in which
      over two out of three monomer units carried a primary amino group formed stable
      colloidal polyplexes with pDNA. Optimized UPC and PEI polyplexes protected the
      pDNA from serum degradation to approximately the same degree, and they gave a
      comparable maximal transgene expression in 293 cells. In contrast to PEI, UPC was
      non toxic at escalating doses. After intratracheal administration, both
      polyplexes distributed to the mid-airways, where transgene expression was
      observed in virtually every epithelial cell, using a sensitive pLacZ reporter
      containing a translational enhancer element. However, the kinetics of gene
      expression differed - PEI polyplexes induced a more rapid onset of gene
      expression than UPC. This was attributed to a more rapid endosomal escape of the
      PEI polyplexes. Although this resulted in a more efficient gene expression with
      PEI polyplexes, UPC had an efficiency comparable to that of commonly used
      cationic lipids. In conclusion, this study provides insights into the use of
      chitosan as a gene delivery system. It emphasises that chitosan is a nontoxic
      alternative to other cationic polymers and it forms a platform for further
      studies of chitosan-based gene delivery systems.

PMID- 11526461
TI  - Dopamine D4 receptor gene (DRD4) is associated with Novelty Seeking (NS) and
      substance abuse: the saga continues...

PMID- 11526462
TI  - Time-dependent sensitization and ECT.

PMID- 11526463
TI  - Association study of cannabinoid receptor gene (CNR1) alleles and drug
      dependence.

PMID- 11526464
TI  - Genetic mechanisms of behavior--don't forget about the transcription factors.
AB  - Major changes in psychiatric phenotypes due to genetic factors are seldom the
      result of single gene polymorphisms, but more often the result of several genetic
      mechanisms. In this millennium article we discuss the notion that the expression
      of numerous candidate genes could be regulated by the same transcription factors,
      and that polymorphisms in transcription factor genes might explain some
      phenotypes. We describe recent results of studies on the biological marker
      thrombocyte monoamine oxidase (trbc MAO) and the transcription factor AP-2beta.
      Low levels of trbc MAO is associated with temperamental characteristics such as
      sensation seeking and impulsiveness, and the enzyme is genetically regulated by
      specific transcriptional mechanisms. Transcription factor AP-2beta is important
      for the development of midbrain structures and AP-2beta has several binding sites
      in the regulatory regions of genes encoding key proteins in the monoamine
      transmitter systems. We have recently shown AP-2beta to be linked to personality,
      binge-eating disorder, treatment with antidepressant drugs, and also to trbc MAO.
      Regardless of whether transcriptions factors, such as AP-2beta, regulate the
      expression of eg, the number of monoamine neurons or a variety of candidate genes
      within the monoamine systems, or both, we would like to emphasize the role of
      transcription factors, besides polymorphisms in monoaminergic candidate genes,
      when explaining inter-individual differences in temperament and psychiatric
      vulnerability.

PMID- 11526465
TI  - Antagonism of nicotinic acetylcholine receptors by inhibitors of monoamine
      uptake.
AB  - A study was made of the effects of several monoamine-uptake inhibitors on
      membrane currents elicited by acetylcholine (ACh-currents) generated by rat
      neuronal alpha2beta4 and mouse muscle nicotinic acetylcholine receptors (AChRs)
      expressed in Xenopus laevis oocytes. For the two types of receptors the monoamine
      uptake inhibitors reduced the ACh-currents albeit to different degrees. The order
      of inhibitory potency was norfluoxetine > clomipramine > indatraline > fluoxetine
      > imipramine > zimelidine > 6-nitro-quipazine > trazodone for neuronal
      alpha2beta4 AChRs, and norfluoxetine > fluoxetine > imipramine > clomipramine >
      indatraline > zimelidine > trazodone > 6-nitro-quipazine for muscle AChRs. Thus,
      the most potent inhibitor was norfluoxetine, whilst the weakest ones were
      trazodone, 6-nitro-quipazine and zimelidine. Effects of the tricyclic
      antidepressant imipramine were studied in more detail. Imipramine inhibited
      reversibly and non-competitively the ACh-current with a similar inhibiting
      potency for both neuronal alpha2beta4 and muscle AChRs. The half-inhibitory
      concentrations of imipramine were 3.65 +/- 0.30 microM for neuronal alpha2beta4
      and 5.57 +/- 0.19 microM for muscle receptors. The corresponding Hill
      coefficients were 0.73 and 1.2 respectively. The inhibition of imipramine was
      slightly voltage-dependent, with electric distances of approximately 0.10 and
      approximately 0.12 for neuronal alpha2beta4 and muscle AChRs respectively.
      Moreover, imipramine accelerated the rate of decay of ACh- currents of both
      muscle and neuronal AChRs. The ACh-current inhibition was stronger when oocytes,
      expressing neuronal alpha2beta4 or muscle receptors, were preincubated with
      imipramine alone than when it was applied after the ACh-current had been
      generated, suggesting that imipramine acts also on non-activated or closed AChRs.
      We conclude that monoamine-uptake inhibitors reduce ACh-currents and that
      imipramine regulates reversibly and non- competitively neuronal alpha2beta4 and
      muscle AChRs through similar mechanisms, perhaps by interacting externally on a
      non-conducting state of the AChR and by blocking the open receptor-channel
      complex close to the vestibule of the channel. These studies may be important for
      understanding the regulation of AChRs as well as for understanding antidepressant
      and side-effects of monoamine-uptake inhibitors.

PMID- 11526467
TI  - Cognitive interference is associated with neuronal marker N-acetyl aspartate in
      the anterior cingulate cortex: an in vivo (1)H-MRS study of the Stroop Color-Word
      task.
AB  - The neurobiology of cognitive interference is unknown. Previous brain imaging
      studies using the Stroop Color-Word (SCW) task indicate involvement of the
      cingulate cortex cognitive division. The present study examines
      interrelationships between regional brain N-Acetyl aspartate (NAA) levels (as
      identified by in vivo proton magnetic resonance spectroscopy in the right and
      left anterior cingulate cortex (ACC), dorsolateral prefrontal cortex,
      orbitofrontal cortex and thalamus) and cognitive interference (as measured by the
      SCW task) in 15 normal subjects. The results show that brain chemistry depends on
      cognitive interference levels (high vs low). Reduction of NAA levels was
      demonstrated in the right ACC (ie, cognitive midsupracallosal division) of high
      interference subjects, as compared to the low interference group (P < 0.01, two
      tailed t-test). Chemical-cognitive relationships were analyzed by calculating
      correlations between regional NAA levels and the SCW task scores. Cognitive
      interference was highly correlated with the right anterior cingulate NAA (r =
      0.76, P < 0.001), and was unrelated to other studied regional NAA, including the
      left ACC (P < 0.025; comparing the difference between r values in the right and
      left ACC). The interrelationships between NAA across brain regions were examined
      using correlation analysis (square matrix correlation maps), which detected
      different connectivity patterns between the two groups. These findings provide
      evidence of ACC involvement in cognitive interference suggesting a possibility of
      neuronal reorganization in the physiological mechanism of interference (most
      likely due to genetically predetermined control of the number of neurons,
      dendrites and receptors, and their function). We conclude that spectroscopic
      brain mapping of NAA, the marker of neuronal density and function, to the SCW
      task measures differentiates between high and low interference in normal
      subjects. This neuroimaging/cognitive tool may be useful for documentation of
      interference in studying cognitive control mechanisms, and in diagnosis of
      neuropsychiatric disorders where dysfunction of cingulate cortex is expected.

PMID- 11526466
TI  - Short- and long-term effect of acetylcholinesterase inhibition on the expression
      and metabolism of the amyloid precursor protein.
AB  - We have investigated the acute and chronic effect of metrifonate (MTF) and
      dichlorvos (DDVP), respectively the prodrug and active acetylcholinesterase
      inhibitor, on the secretory processing of the amyloid precursor protein (APP) in
      SH-SY5Y neuroblastoma cells. We demonstrate that the acute treatment of SH-SY5Y
      cells with both compounds results in an increased secretion of the soluble
      fragment of APP (sAPPalpha) into the conditioned media of cells, with a pattern
      correlated to the level of acetycholinesterase inhibition. The regulation of APP
      processing in these conditions is mediated by an indirect cholinergic effect on
      muscarinic receptors, as demonstrated by inhibition with atropine. We have also
      followed APP expression and metabolism after long-term treatment with
      metrifonate. Treated cells showed reduced AChE activity after 24, 48 h and also
      following 7 days of repeated treatment, a time point at which increased AChE
      expression was detectable. At all time points sAPPalpha release was unaffected
      suggesting that enhanced sAPPalpha release by MTF is transitory, nevertheless the
      sensitivity of cholinergic receptors was unchanged, as indicated by the fact that
      cholinergic response can be elicited similarly in untreated and treated cells.
      APP gene expression was unaffected by long-term AChE inhibition suggesting that
      increased short-term sAPPalpha release does not elicit compensatory effects.

PMID- 11526468
TI  - Expression of corticotropin releasing hormone receptors type I and type II mRNA
      in suicide victims and controls.
AB  - Corticotropin-releasing hormone (CRH) is a key neuroendocrine factor implementing
      endocrine, immune and behavioral responses to stress. CRH exerts its action
      through two major receptors, CRH-R1 and CRH-R2. Recently novel non-peptidic
      antagonists directed against CRH-R1 or CRH-R2 have been proposed as promising
      agents in the treatment of depression, anxiety and eating disorder. However, so
      far the CRH-receptor system has not been widely studied in humans. Therefore, we
      employed quantitative TaqMan PCR to analyze the expression and distribution of
      both CRH-R1 and CRH-R2 in human brain tissue and peripheral organs. Furthermore
      the expression of CRH receptors was analyzed for the first time in pituitaries of
      suicide victims by in situ hybridization and quantitative PCR. Our data
      demonstrated a different expression pattern in humans as compared to rodents.
      Both CRH-R1 and CRH-R2 were expressed in high amounts in the brain with the
      strongest expression in the pituitary. As described in rodents, however the CRH
      R1 in human was the predominant receptor in the brain (82.7 +/- 11.0%), whilst
      CRH-R2 was the predominant receptor in peripheral organs (77.0 +/- 15.8%). There
      was a shift in the ratio of CRH-R1/R2 in the pituitaries of suicide victims. In
      conclusion, both CRH-R1 and CRH-R2 are widely expressed in human tissues with a
      distribution substantially different from rodents. Strong expression of both CRH
      R1 and CRH-R2 in human pituitaries suggests that particularly under stress,
      activation of the HPA axis can be maintained through both receptors.

PMID- 11526469
TI  - St John's wort, hypericin, and imipramine: a comparative analysis of mRNA levels
      in brain areas involved in HPA axis control following short-term and long-term
      administration in normal and stressed rats.
AB  - Clinical studies demonstrate that the antidepressant efficacy of St John's wort
      (Hypericum) is comparable to that of tricyclic antidepressants such as
      imipramine. Onset of efficacy of these drugs occurs after several weeks of
      treatment. Therefore, we used in situhybridization histochemistry to examine in
      rats the effects of short-term (2 weeks) and long-term (8 weeks) administration
      of imipramine, Hypericum extract, and hypericin (an active constituent of St
      John's wort) on the expression of genes that may be involved in the regulation of
      the hypothalamic-pituitary-adrenal (HPA) axis. Imipramine (15 mg kg(-1)),
      Hypericum (500 mg kg(-1)), and hypericin (0.2 mg kg(-1)) given daily by gavage
      for 8 weeks but not for 2 weeks significantly decreased levels of corticotropin
      releasing hormone (CRH) mRNA by 16-22% in the hypothalamic paraventricular
      nucleus (PVN) and serotonin 5-HT(1A) receptor mRNA by 11-17% in the hippocampus.
      Only imipramine decreased tyrosine hydroxylase (TH) mRNA levels in the locus
      coeruleus (by 23%), and only at 8 weeks. The similar delayed effects of the three
      compounds on gene transcription suggests a shared action on the centers that
      control HPA axis activity. A second study was performed to assess the effects of
      long-term imipramine and Hypericum administration on stress-induced changes in
      gene transcription in stress-responsive circuits. Repeated immobilization stress
      (2 h daily for 7 days) increased mRNA levels of CRH in the PVN,
      proopiomelanocortin (POMC) in the anterior pituitary, glutamic acid decarboxylase
      (GAD 65/67) in the bed nucleus of the stria terminalis (BST), cyclic AMP response
      element binding protein (CREB) in the hippocampus, and TH in the locus coeruleus.
      It decreased mRNA levels of 5-HT(1A) and brain-derived neurotrophic factor (BDNF)
      in the hippocampus. Long-term pre-treatment with either imipramine or Hypericum
      reduced to control levels the stress-induced increases in gene transcription of
      GAD in the BST, CREB in the hippocampus, and POMC in the pituitary. The stress
      induced increases in mRNA levels of CRH in the PVN and TH in the locus coeruleus
      were reduced by imipramine but not by Hypericum. The stress-induced decreases in
      BDNF and 5-HT(1A)mRNA levels were not prevented by either drug. Taken together,
      these data show: (1) that Hypericum and hypericin have delayed effects on HPA
      axis control centers similar to those of imipramine; and (2) that select stress
      induced changes in gene transcription in particular brain areas can be prevented
      by long-term treatment with either the prototypic tricyclic antidepressant
      imipramine or the herbiceutical St John's wort. However, imipramine appears to be
      more effective in blocking stress effects on the HPA axis than the plant extract.

PMID- 11526470
TI  - Association and linkage studies between bipolar affective disorder and the
      polymorphic CAG/CTG repeat loci ERDA1, SEF2-1B, MAB21L and KCNN3.
AB  - Several reports have suggested the presence of anticipation in bipolar affective
      disorder (BPAD). In addition, independent studies using the RED (repeat expansion
      detection) have shown association between BPAD and longer CAG/CTG repeats.
      Therefore loci with large CAG/CTG repeats are plausible candidates in the
      inheritance of BPAD. The present study assesses the length of the repeats in four
      loci: the ERDA-1 locus which is known to account for most of the long CAG repeats
      detected by RED, the SEF2-1b locus which is placed in a region where positive
      linkage results have been reported and the loci MAB21L and KCNN3 as functional
      candidate genes. A Brazilian case-control sample with 115 unrelated BPAD patients
      and 196 healthy control subjects and 14 multiply affected bipolar families was
      investigated. With the case-control design the distribution of alleles between
      the two groups did not approach statistical significance. The extended
      transmission disequilibrium test (ETDT) performed in our families did not show
      evidence for linkage disequilibrium. Parametric and non-parametric linkage
      analysis also did not provide support for linkage between any of the four loci
      and BPAD. Our data do not support the hypothesis that variation at the
      polymorphic CAG/CTG repeat loci ERDA-1, SEF2-1b, MAB21L or KCNN3 influence
      susceptibility to BPAD in our sample.

PMID- 11526471
TI  - Mapping susceptibility genes for bipolar disorder: a pharmacogenetic approach
      based on excellent response to lithium.
AB  - Genetic mapping studies in bipolar disorder (BD) have been hampered by the
      unclear boundaries of the phenotypic spectrum, and possibly, by the complexity of
      the underlying genetic mechanisms, and heterogeneity. Among the suggested
      approaches to circumvent these problems, a pharmacogenetic strategy has been
      increasingly proposed. Several studies have indicated that patients with BD who
      respond well to lithium prophylaxis constitute a biologically distinct subgroup.
      In this study we have conducted a complete genome scan using 378 markers spaced
      at an average distance of 10 cM in 31 families ascertained through excellent
      lithium responders. Response to lithium was evaluated prospectively with an
      average follow-up of 12 years. Evidence for linkage was found with a locus on
      chromosome 15q14 (ACTC, lod score = 3.46, locus-specific P-value = 0.000014) and
      suggestive results were observed for another marker on chromosome 7q11.2
      (D7S1816, lod score = 2.68, locus-specific P-value = 0.00011). Other interesting
      findings were obtained with markers on chromosomes 6 and 22, namely D6S1050 (lod
      score = 2.0, locus-specific P-value = 0.00004) and D22S420 (lod score = 1.91).
      Nonparametric linkage analysis provided additional support for the role of these
      loci. Further analyses of these results suggested that the locus on chromosome
      15q14 may be implicated in the etiology of BD, whereas the 7q11.2 locus may be
      relevant for lithium response. In conclusion, our results provide original
      evidence suggesting that loci on 15q14 and 7q11.2 may be implicated in the
      pathogenesis of BD responsive to lithium.

PMID- 11526473
TI  - Influence of tryptophan hydroxylase and serotonin transporter genes on
      fluvoxamine antidepressant activity.
AB  - The aim of the present study was to test a possible effect of the A218C
      tryptophan hydroxylase (TPH) gene variant on the antidepressant activity of
      fluvoxamine in a sample of major and bipolar depressives, with or without
      psychotic features. Two hundred and seventeen inpatients were treated with
      fluvoxamine 300 mg and either placebo or pindolol in a double blind design for 6
      weeks. The severity of depressive symptoms was weekly assessed with the Hamilton
      Rating Scale for Depression. TPH allelic variants were determined in each subject
      by using a PCR-based technique. No significant finding was observed in the
      overall sample as well as in the pindolol group, while TPH*A/A was associated
      with a slower response to fluvoxamine treatment in subjects not taking pindolol
      (P = 0.001). This effect was independent from the previously reported influence
      of 5-HTTLPR polymorphism. If confirmed, these results may shed further light on
      the genetically determined component of the response to pharmacological
      treatments, thus helping the clinician to individualize each patient's therapy
      according to their genetic pattern.

PMID- 11526472
TI  - Variability of 5-HT2C receptor cys23ser polymorphism among European populations
      and vulnerability to affective disorder.
AB  - Substantial evidence supports a role for dysfunction of brain serotonergic (5-HT)
      systems in the pathogenesis of major affective disorder, both unipolar (recurrent
      major depression) and bipolar.(1) Modification of serotonergic neurotransmission
      is pivotally implicated in the mechanism of action of antidepressant drugs(2) and
      also in the action of mood stabilizing agents, particularly lithium carbonate.(3)
      Accordingly, genes that code for the multiple subtypes of serotonin receptors
      that have been cloned and are expressed in brain,(4) are strong candidates for a
      role in the genetic etiology of affective illness. We examined a structural
      variant of the serotonin 2C (5-HT2C) receptor gene (HTR2C) that gives rise to a
      cysteine to serine substitution in the N terminal extracellular domain of the
      receptor protein (cys23ser),(5) in 513 patients with recurrent major depression
      (MDD-R), 649 patients with bipolar (BP) affective disorder and 901 normal
      controls. The subjects were drawn from nine European countries participating in
      the European Collaborative Project on Affective Disorders. There was significant
      variation in the frequency of the HT2CR ser23 allele among the 10 population
      groups included in the sample (from 24.6% in Greek control subjects to 9.2% in
      Scots, chi(2) = 20.9, df 9, P = 0.01). Logistic regression analysis demonstrated
      that over and above this inter-population variability, there was a significant
      excess of HT2CR ser23 allele carriers in patients compared to normal controls
      that was demonstrable for both the MDD (chi(2) = 7.34, df 1, P = 0.006) and BP
      (chi(2) = 5.45, df 1, P = 0.02) patients. These findings support a possible role
      for genetically based structural variation in 5-HT2C receptors in the
      pathogenesis of major affective disorder.

PMID- 11526474
TI  - Neurotrophin-3 modulates noradrenergic neuron function and opiate withdrawal.
AB  - Somatic symptoms and aversion of opiate withdrawal, regulated by noradrenergic
      signaling, were attenuated in mice with a CNS-wide conditional ablation of
      neurotrophin-3. This occurred in conjunction with altered cAMP-mediated
      excitation and reduced upregulation of tyrosine hydroxylase in A6 (locus
      coeruleus) without loss of neurons. Transgene-derived NT-3 expressed by
      noradrenergic neurons of conditional mutants restored opiate withdrawal symptoms.
      Endogenous NT-3 expression, strikingly absent in noradrenergic neurons of
      postnatal and adult brain, is present in afferent sources of the dorsal medulla
      and is upregulated after chronic morphine exposure in noradrenergic projection
      areas of the ventral forebrain. NT-3 expressed by non-catecholaminergic neurons
      may modulate opiate withdrawal and noradrenergic signalling.

PMID- 11526476
TI  - The tumor suppressor protein menin interacts with NF-kappaB proteins and inhibits
      NF-kappaB-mediated transactivation.
AB  - Multiple endocrine neoplasia type 1 is an autosomal dominant tumor syndrome.
      Manifestations include neoplasms of the parathyroid glands, enteropancreatic
      neuroendocrine cells, and the anterior pituitary gland. The MEN1 tumor suppressor
      gene encodes menin, a 610 amino acid nuclear protein without sequence homology to
      other proteins. To elucidate menin function, we used immunoprecipitation to
      identify interacting proteins. The NF-kappaB proteins p50, p52 and p65 were found
      to interact specifically and directly with menin in vitro and in vivo. The region
      of NF-kappaB proteins sufficient for binding to menin is the N-terminus.
      Furthermore, amino acids 305-381 of menin are essential for this binding. Menin
      represses p65-mediated transcriptional activation on NF-kappaB sites in a dose
      dependent and specific manner. Also, PMA (phorbol 12-myristate 13-acetate)
      stimulated NF-kappaB activation is suppressed by menin. These observations
      suggest that menin's ability to interact with NF-kappaB proteins and its
      modulation of NF-kappaB transactivation contribute to menin's tumor suppressor
      function.

PMID- 11526477
TI  - Inhibition of v-Abl transformation in 3T3 cells overexpressing different forms of
      the Abelson interactor protein Abi-1.
AB  - The abi-1 gene encodes a protein that binds and is phosphorylated by the Abelson
      protein tyrosine kinase. Constructs expressing a full-length abi-1 cDNA, and a
      smaller cDNA arising from an alternatively spliced form, were generated and
      tested for their effect on transformation of NIH3T3 cells by the Abelson murine
      leukemia virus. Overexpression of both forms of the protein strongly inhibited
      transformation by the wild-type P160 strain of the virus, but not by the non
      interacting mutant P90A strain. The inhibition required the SH3 domain of Abi-1,
      suggesting that a direct interaction was required for the effect. Rare
      breakthrough P160 transformants of the Abi-1 overexpressing lines were found to
      have downregulated Abi-1 protein levels by a post-transcriptional mechanism.

PMID- 11526478
TI  - Cleavage of Fyn and Lyn in their N-terminal unique regions during induction of
      apoptosis: a new mechanism for Src kinase regulation.
AB  - The members of the Src kinase family are expressed in a wide variety of tissues,
      but some of them such as Blk, Hck, Fgr, Lck and Lyn are found primarily in
      hematopoietic cells. In the present study, we have undertaken experiments to test
      whether Src kinase cleavage and relocation is a general mechanism during
      induction of apoptosis. Our results indicate that Fyn and Lyn are efficiently
      cleaved in their unique region in hematopoietic cells undergoing apoptosis. Fyn
      cleavage occurred in Fas-stimulated Jurkat T cells but Fyn and Lyn were also
      processed in the SKW6.4 B cell line. Inhibition of caspases by Z-VAD-fmk or Ac
      DEVD-CHO totally prevented Fyn and Lyn cleavage in both intact cells and in
      vitro. Fyn and Lyn but not Lck, Src and Hck were processed in vitro by human
      recombinant caspase 3 and by cellular extracts prepared from Fas-stimulated
      cells. Single mutation of Asp 19 or Asp 18 in the unique N-terminal domains of
      Fyn and Lyn respectively abolished their cleavage and relocation into the
      cytoplasm of apoptotic cells. When immunoprecipitated from COS cells N-terminal
      deleted Src kinases exhibited increased enzymatic kinase activity toward enolase.
      Thus, cleavage of Fyn and Lyn during induction of apoptosis represents a new
      mechanism for the regulation of Src kinases that may have important functional
      and physiological consequences.

PMID- 11526479
TI  - IGF-II induces rapid beta-catenin relocation to the nucleus during epithelium to
      mesenchyme transition.
AB  - The epithelium to mesenchyme transition is thought to play a fundamental role
      during embryonic development and tumor progression. Loss of cell-cell adhesion
      and modification of both cell morphology and gene expression are the main events
      associated with this transition. There is a large amount of evidence suggesting
      that growth factors can initiate these events. Yet, the connection from growth
      factor induction to changes in cell adhesion and morphology is largely unknown.
      To elucidate this connection, we have investigated the action of IGF-II on E
      cadherin/beta-catenin complex-mediated cell-cell adhesion and on beta-catenin/TCF
      3 mediated gene expression. We can show that (1) IGF-II induces a rapid
      epithelium to mesenchymal transition; (2) IGF1R, the receptor for IGF-II, belongs
      to the same membrane complex as E-cadherin and beta-catenin; (3) IGF-II induces a
      redistribution of beta-catenin from the plasma membrane to the nucleus and an
      intracellular sequestration and degradation of E-cadherin; (4) IGF-II induces the
      transcription of beta-catenin/TCF-3 target genes. Based on the given case of IGF
      II and E-cadherin/beta-catenin complex, this study reveals the backbone of a
      cascade connecting growth factor signaling with cell-cell adhesion during EMT.

PMID- 11526480
TI  - Polyoma virus disrupts ARF signaling to p53.
AB  - Polyoma virus (Py) differs from other small DNA tumor viruses in not encoding a
      protein that inactivates p53. The complete Py early region encoding the large T
      antigen (PyLT), middle T-antigen (PyMT) and small T-antigen (PyST) will transform
      primary rodent cells and REF52 cells, but PyMT, the main Py oncogene, by itself
      will only transform these cells when p53 or ARF is inactivated. We have related
      Py oncogene cooperation with the effects of the Py T-antigens on the ARF-p53
      signaling pathway. PyMT activates an ARF-induced p53-mediated block to cell
      division explaining the inability of PyMT alone to generate dividing transformed
      cells. In contrast, in REF52 cells transformed by the whole Py early region
      (PyREF52), ARF is upregulated but p53 is not activated. Thus PyLT and/or PyST
      negates the PyMT-induced ARF-mediated block to cell division by disrupting the
      signaling pathway from ARF to p53. Although there is no detectable interaction or
      co-localization of endogenous ARF (nucleoli) and MDM2 (nucleoplasm) in PyREF52
      cells, expression of transfected ectopic ARF results in an MDM2/ARF interaction
      and sequestration of MDM2 into the nucleoli. Sequestration of MDM2 by ARF in the
      nucleoli is not essential for a p53 response in REF52 cells as activation of Raf
      in REF52Raf-ER cells results in an ARF-induced p53-mediated cell cycle block in
      the absence of a detectable ARF-MDM2 interaction. Py may provide new insights
      into the cellular ARF-p53 signaling pathway.

PMID- 11526481
TI  - The Brn-3b POU family transcription factor regulates the cellular growth,
      proliferation, and anchorage dependence of MCF7 human breast cancer cells.
AB  - The Brn-3b POU domain containing transcription factor is expressed in the
      developing sensory nervous system as well as in epithelial cells of the breast,
      cervix, and testes. Brn-3b functionally interacts with the estrogen receptor (ER)
      and in association with the ER, regulates transcription from estrogen responsive
      genes. In addition, Brn-3b expression is elevated in breast tumours compared to
      levels in normal mammary cells. To explore the role of Brn-3b in breast cancer,
      we established stable cell lines derived from the MCF7 human breast cancer cell
      line which had been transfected with Brn-3b sense or anti-sense constructs. The
      Brn-3b over-expressing cell lines exhibited increased growth rate, reached
      confluence at a higher saturation density, had higher proliferative activity, and
      an enhanced ability to form colonies in soft agar when compared to the control
      empty vector transfected cells. Likewise, the Brn-3b anti-sense cell lines showed
      reduced cellular growth and proliferation, reached confluence at a lower density,
      and exhibited a decreased ability to form colonies in soft agar when compared to
      the vector controls. Five to ten per cent of the Brn-3b over-expressing cells
      exhibited a severely altered morphology characterized by reduced adherence to
      tissue culture plastic, increased cell size, and a vacuolar cell shape. These
      results thus further indicate a role for the Brn-3b transcription factor in
      regulating mammary cell growth and suggest that its elevation in breast cancer is
      of functional significance.

PMID- 11526482
TI  - Different effects of p14ARF on the levels of ubiquitinated p53 and Mdm2 in vivo.
AB  - Mdm2 has been shown to promote its own ubiquitination and the ubiquitination of
      the p53 tumour suppressor by virtue of its E3 ubiquitin ligase activity. This
      modification targets Mdm2 and p53 for degradation by the proteasome. The p14ARF
      tumour suppressor has been shown to inhibit degradation of p53 mediated by Mdm2.
      Several models have been proposed to explain this effect of p14ARF. Here we have
      compared the effects of p14ARF overexpression on the in vivo ubiquitination of
      p53 and Mdm2. We report that the inhibition of the Mdm2-mediated degradation of
      p53 by p14ARF is associated with a decrease in the proportion of ubiquitinated
      p53. The levels of polyubiquitinated p53 decreased preferentially compared to
      monoubiquitinated species. p14ARF overexpression increased the levels of Mdm2 but
      it did not reduce the overall levels of ubiquitinated Mdm2 in vivo. This is
      unexpected because p14ARF has been reported to inhibit the ubiquitination of Mdm2
      in vitro. In addition we show that like p14ARF, the proteasome inhibitor MG132
      can promote the accumulation of Mdm2 in the nucleolus and that this can occur in
      the absence of p14ARF expression. We also show that the mutation of the nucleolar
      localization signal of Mdm2 does not impair the overall ubiquitination of Mdm2
      but is necessary for the effective polyubiquitination of p53. These studies
      reveal important differences in the regulation of the stability of p53 and of
      Mdm2.

PMID- 11526483
TI  - A DNA microarray screen for genes involved in c-MYC and N-MYC oncogenesis in
      human tumors.
AB  - MYC proto-oncogenes play a major role in various types of human tumors. The
      products of these genes are transcription factors that bind to specific sequences
      and activate the expression of target genes. Identifying these target genes and
      their downstream effectors is a crucial step in understanding and preventing MYC
      induced oncogenesis. Until now, most of the efforts to identify such genes were
      performed by analysing in vitro systems whose relevance to the malignant process
      in vivo remains unclear. We aimed at identifying genes that play a major role in
      the malignant process of MYC induced carcinogenesis. Thus, we analysed the
      expression profiles of human MYC induced tumors and compared them to similar, non
      MYC tumors. Moreover, we looked for the common characteristics of different types
      of MYC induced tumors. We identified several genes, most of them involved in cell
      cycle regulation, that are over expressed in MYC induced lymphomas as well as MYC
      induced neuronal-like tumors. In order to determine whether MYC induced
      oncogenesis is similar in human and in the mouse model system, we analysed the
      expression of the identified genes in cells derived from transgenic mice tumors.
      We also present the distribution of MYC putative binding sites in the regulatory
      sequences of the genes identified in our analysis. This analysis pointed to two
      genes (E2F1 and TSC2) as candidates to be targets of Myc activity. We thus
      further analysed the expression of these genes in the tumor cell lines, and
      examined the plausibility that elements in their promoter bind the Myc protein.
      Our data points to several genes that may be involved in c-MYC and N-MYC induced
      tumors and to two genes that may be targets for MYC activity.

PMID- 11526484
TI  - Integrin signaling inhibits paclitaxel-induced apoptosis in breast cancer cells.
AB  - Inherent or acquired drug resistance is one of the major problems in
      chemotherapy. The mechanisms by which cancer cells survive and escape the
      cytotoxic effects of chemotherapeutic agents are essentially unknown. In the
      present study, we demonstrate that in the MDA-MB-231 and MDA-MB-435 breast cancer
      cells, ligation of beta1 integrins by their extracellular matrix ligands inhibits
      significantly apoptosis induced by paclitaxel and vincristine, two microtubule
      directed chemotherapeutic agents that are widely used in the therapy of breast
      cancer. We show that beta1 integrin signaling inhibits drug-induced apoptosis by
      inhibiting the release of cytochrome c from the mitochondria in response to drug
      treatment. Further, integrin-mediated protection from drug-induced apoptosis and
      inhibition of cytochrome c release are dependent on the activation of the PI 3
      kinase/Akt pathway. Our results identify beta1 integrin signaling as an important
      survival pathway in drug-induced apoptosis in breast cancer cells and suggest
      that activation of this pathway may contribute to the generation of drug
      resistance.

PMID- 11526485
TI  - Genetic mapping and DNA sequence-based analysis of deleted regions on chromosome
      16 involved in progression of bladder cancer from occult preneoplastic conditions
      to invasive disease.
AB  - Histologic and genetic mapping with 30 hypervariable markers mapped to chromosome
      16 were performed on 234 DNA samples of five cystectomy specimens from patients
      with invasive bladder cancer. Allelic losses of individual markers were related
      to microscopically identified precursor conditions in the entire bladder mucosa
      and invasive cancer. Their significance for the development and progression of
      neoplasia from in situ preneoplastic conditions to invasive disease was analysed
      by the nearest neighbor algorithm and binomial maximum likelihood analysis. Using
      this approach we identified five distinct regions of allelic losses defined by
      their flanking markers and predicted size as follows. p13.3(D16S418-D16S406, 1.2
      cM), p13.1(D16S748-D16S287, 12.9 cM), q12 1(D16S409-D16S514, 24.0 cM), q22.1
      (D16S496-D16S515, 5.4 cM), and q24 (D16S507-D16S511, 5.9 cM and D16S402-D16S413,
      17.4 cM). The regions mapping to p13.1 and q24 were involved in early
      intraurothelial phases of bladder neoplasia such as mild to moderate dysplasia.
      On the other hand the deleted region mapping to p13.3 was involved in progression
      of severe dysplasia/carcinoma in situ to invasive bladder cancer. Testing of
      markers that exhibited statistically significant LOH in relation to progression
      of neoplasia from precursor conditions to invasive cancer on 28 tumors and voided
      urine samples from 25 patients with bladder cancer revealed that q12.1 showed LOH
      in 46.4% of tumor and 32.0% of voided urine samples. The LOH of a single marker
      D16S541 could be detected in approximately 28% of tumors and 20% of voided urine
      samples of patients with bladder cancer. These data imply that the deleted region
      centered around marker D16S541 spanning approximately 10 cM and flanked by
      D16S409 and D16S415 contains a novel putative tumor suppressor gene or genes
      playing an important role in the development of human bladder cancer. To
      facilitate more precise positional mapping and identification of pathogenetically
      relevant genes, we analysed of human genome contig and sequence databases
      spanning the deleted regions. Multiple known candidate genes and several smaller
      gene-rich areas mapping to the target regions of chromosome 16 were identified.

PMID- 11526486
TI  - Hepatocellular expression of a dominant-negative mutant TGF-beta type II receptor
      accelerates chemically induced hepatocarcinogenesis.
AB  - The potent growth-inhibitory activity of cytokines of the transforming growth
      factor-beta (TGF-beta) superfamily and their widespread expression in epithelia
      suggest that they may play an important role in the maintenance of epithelial
      homeostasis. To analyse TGF-beta mediated tumor suppressor activity in the liver,
      we generated transgenic mice overexpressing a dominant negative type II TGF-beta
      receptor in hepatocytes under control of the regulatory elements of the human C
      reactive protein gene promoter. Transgenic animals exhibited constitutive and
      liver-specific transgene expression. The functional inactivation of the TGF-beta
      signaling pathway in transgenic hepatocytes was shown by reduced TGF-beta induced
      inhibition of DNA synthesis in primary hepatocyte cultures. Liver morphology and
      spontaneous tumorigenesis were unchanged in transgenic mice suggesting that
      interruption of the signaling of all three isoforms of TGF-beta in hepatocytes
      does not disturb tissue homeostasis in the liver under physiological conditions.
      However, following initiation with the carcinogen diethylnitrosamine and tumor
      promotion with phenobarbital transgenic mice exhibited a moderate albeit
      significant increase in the incidence, size and multiplicity of both
      preneoplastic tissue lesions in the liver and of hepatocellular carcinomas. These
      results give in vivo evidence for a tumor suppressor activity of the endogenous
      TGF-beta system in the liver during chemical hepatocarcinogenesis.

PMID- 11526487
TI  - Extensive characterization of genetic alterations in a series of human colorectal
      cancer cell lines.
AB  - A number of genetic alterations have been described in colorectal cancers. They
      include allelic losses on specific chromosomal arms, mutations of oncogenes,
      tumor suppressor genes and mismatch repair genes, microsatellite instability in
      coding repeat sequences of target genes and methylation defects in gene
      promoters. Since these alterations have been reported by different groups on
      different tumors and cell lines, the complete repertoire of genetic alterations
      for any given tumor sample remains unknown. In the present study, we analysed a
      series of 22 colorectal cancer cell lines for 31 different genetic alterations.
      We found significant correlations between mutational profiles in these colorectal
      cell lines associated with differences in mismatch repair status. This panel of
      colon cancer cell lines is representative of the genetic heterogeneity occurring
      in sporadic colorectal carcinoma. Our results may prove to be very useful for
      understanding the different biological pathways involved in the development of
      colon cancer, and for groups studying cellular biology and pharmacology on the
      same cell lines.

PMID- 11526488
TI  - Aberrant promoter methylation of previously unidentified target genes is a common
      abnormality in medulloblastomas--implications for tumor biology and potential
      clinical utility.
AB  - Medulloblastomas exhibit an array of diverse cytogenetic abnormalities. To
      evaluate the significance of epigenetic rather than genetic lesions in
      medulloblastomas and other primitive neuroectodermal tumors (PNETs) of the
      childhood CNS we performed a systematic analysis of gene specific and global
      methylation. Methylation-specific PCR detected no methylation for p15(INK4B), von
      Hippel Lindau and TP53 and only limited methylation for E-Cadherin and p16(INK4A)
      in tumors. The cell lines Daoy and MHH-PNET-5 in which the p16(INK4A) promoter
      was methylated did not express the gene, but demonstrated abnormalities by SSCP.
      Immunohistochemistry for p16 was negative in all examined normal cerebella and
      medulloblastomas. Using the technique of Restriction Landmark Genomic Scanning we
      detected methylation affecting up to 1% of all CpG islands in primary MB/PNETs
      and 6% in MB cell lines. Methylation patterns differed between medulloblastomas
      and PNETs. Examination of several methylated sequences revealed homologies to
      known genes and expressed sequences. Analysis of survival data identified seven
      of 30 hypermethylated sequences significantly correlating with poor prognosis. We
      suggest that DNA hypermethylation has an outstanding potential for the
      identification of novel tumor suppressors as well as diagnostic and therapeutic
      targets in MBs and other PNETs of the CNS.

PMID- 11526489
TI  - Ionizing radiation but not anticancer drugs causes cell cycle arrest and failure
      to activate the mitochondrial death pathway in MCF-7 breast carcinoma cells.
AB  - There is considerable evidence that ionizing radiation (IR) and chemotherapeutic
      drugs mediate apoptosis through the intrinsic death pathway via the release of
      mitochondrial cytochrome c and activation of caspases -9 and -3. Here we show
      that MCF-7 cells that lack caspase-3 undergo a caspase-dependent apoptotic cell
      death in the absence of DNA fragmentation and alpha-fodrin cleavage following
      treatment with etoposide or doxorubicin, but not after exposure to IR. Re
      expression of caspase-3 restored DNA fragmentation and alpha-fodrin cleavage
      following drug treatment, but it did not alter the radiation-resistant phenotype
      of these cells. In contrast to the anticancer drugs, IR failed to induce the
      intrinsic death pathway in MCF-7/casp-3 cells, an event readily observed in IR
      induced apoptosis of HeLa cells. Although IR-induced DNA double-strand breaks
      were repaired with similar efficiencies in all cell lines, cell cycle analyses
      revealed a persistent G2/M arrest in the two MCF-7 cell lines, but not in HeLa
      cells. Together, our data demonstrate that caspase-3 is required for DNA
      fragmentation and alpha-fodrin cleavage in drug-induced apoptosis and that the
      intrinsic death pathway is fully functional in MCF-7 cells. Furthermore, they
      show that the radiation-resistant phenotype of MCF-7 cells is not due to the lack
      of caspase-3, but is caused by the failure of IR to activate the intrinsic death
      pathway. We propose (1) different signaling pathways are induced by anticancer
      drugs and IR, and (2) IR-induced G2/M arrest prevents the generation of an
      apoptotic signal required for the activation of the intrinsic death pathway.

PMID- 11526490
TI  - STI571 inactivation of the gastrointestinal stromal tumor c-KIT oncoprotein:
      biological and clinical implications.
AB  - Mutations in the c-KIT receptor occur somatically in many sporadic
      Gastrointestinal Stromal Tumors (GIST), and similar mutations have been
      identified at the germline level in kindreds with multiple GISTs. These mutations
      activate the tyrosine kinase activity of c-KIT and induce constitutive signaling.
      To investigate the function of activated c-KIT in GIST, we established a human
      GIST cell line, GIST882, which expresses an activating KIT mutation (K642E) in
      the first part of the cytoplasmic split tyrosine kinase domain. Notably, the
      K642E substitution is encoded by a homozygous exon 13 missense mutation, and,
      therefore, GIST882 cells do not express native KIT. GIST882 c-KIT protein is
      constitutively tyrosine phosphorylated, but tyrosine phosphorylation was rapidly
      and completely abolished after incubating the cells with the selective tyrosine
      kinase inhibitor STI571. Furthermore, GIST882 cells evidenced decreased
      proliferation and the onset of apoptotic cell death after prolonged incubation
      with STI571. Similar results were obtained after administering STI571 to a
      primary GIST cell culture that expressed a c-KIT exon 11 juxtamembrane mutation
      (K558NP). These cell-culture-based studies support an important role for c-KIT
      signaling in GIST and suggest therapeutic potential for STI571 in patients
      afflicted by this chemoresistant tumor.

PMID- 11526491
TI  - No evidence of somatic FGFR3 mutation in various types of carcinoma.
AB  - Germline specific point mutations in the gene encoding fibroblast growth factor
      receptor 3 (FGFR3) are associated with autosomal dominant human skeletal
      dysplasia and craniosynostosis syndromes. Mutations identical to the germinal
      activating mutations found in severe skeletal dysplasias have been identified in
      certain types of cancer: at low frequency in multiple myeloma and cervix
      carcinoma and at high frequency in bladder carcinoma. We analysed, by SSCP and
      sequencing, the prevalence of FGFR3 mutations in 116 primary tumours of various
      types (upper aerodigestive tract, oesophagus, stomach, lung and skin). The
      regions analysed encompassed all FGFR3 point mutations previously described in
      severe skeletal dysplasia and cancers. No mutations were detected in the tumour
      types examined, suggesting that FGFR3 mutations are restricted to a few tumour
      types, the evidence to date suggesting that they are very specific to bladder
      carcinomas.

PMID- 11526492
TI  - Identification of AXUD1, a novel human gene induced by AXIN1 and its reduced
      expression in human carcinomas of the lung, liver, colon and kidney.
AB  - Axin, an important regulator of beta-catenin, is frequently mutated in human
      hepatocellular carcinomas (HCCs), and transduction of the wild-type Axin gene
      (AXIN1) induces apoptosis in HCC cells as well as in colon cancer cells. To
      investigate the detailed biological function of Axin, we searched on a cDNA
      microarray for genes whose expression was altered by transfer of wild-type AXIN1
      into colon-cancer cell line LoVo. Among the genes showing altered expression, we
      focused on one, termed AXUD1 (AXIN1 up-regulated), that revealed enhanced
      expression in response to exogenously expressed AXIN1 but not to LacZ, a control
      gene. The AXUD1 gene consists of five exons and encodes a transcript with an open
      reading frame of 1767 bp. A 3.2-kb transcript of AXUD1 was expressed in all human
      tissues examined, most abundantly in lung, placenta, skeletal muscle, pancreas
      and leukocyte. By radiation-hybrid mapping we assigned its chromosomal location
      at 3p22, a region where frequent loss of heterozygosity has been reported in
      lung, renal, prostate, breast and cervical cancers. AXUD1 was frequently down
      regulated in lung, kidney, liver and colon cancers compared with their
      corresponding normal tissues, suggesting that AXUD1 may have a tumor-suppressor
      function in those organs.

PMID- 11526494
TI  - Genomic structure and mutational analysis of the human KIF1B gene which is
      homozygously deleted in neuroblastoma at chromosome 1p36.2.
AB  - In order to clone candidate tumor suppressor genes whose loss contributes to the
      pathogenesis of neuroblastoma (NB), we performed polymerase chain reaction (PCR)
      screening using a high-density sequence tagged site-content map within a commonly
      deleted region (chromosome band 1p36) in 24 NB cell lines. We found a
      approximately 480 kb homozygously deleted region at chromosome band 1p36.2 in one
      of the 24 NB cell lines, NB-1, and cloned the human homologue (KIF1B-beta) of the
      mouseKif1B-beta gene in this region. The KIF1B-beta gene had at least 47 exons,
      all of which had a classic exon-intron boundary structure. Mouse Kif1B is a
      microtubule-based putative anterograde motor protein for the transport of
      mitochondria in neural cells. We performed mutational analysis of the KIF1B-beta
      gene in 23 cell lines using 46 sets of primers and also an allelic imbalance (AI)
      analysis of KIF1B-beta in 50 fresh NB samples. A missense mutation at codon 1554,
      GTG (Gly) to ATG (Met), silent mutations at codon 409 (ACG to ACA) and codon 1721
      (ACC to ACT), and polymorphisms at codon 170, GAT (Asp) to GAA (Glu), and at
      codon 1087, TAT (Tyr), to TGT (Cys), were all identified, although their
      functional significances remain to be determined. The AI for KIF1B-beta was
      slightly higher (38%) than those for the other two markers (D1S244, D1S1350) (35
      and 32%) within the commonly deleted region (1p36). Reverse transcriptase-PCR
      analysis of the KIF1B-beta gene revealed obvious expression in all NB cell lines
      except NB-1, although decreased expression of the KIF1B-beta gene was found in a
      subset of early- and advanced-stage NBs. These results suggest that the KIF1B
      beta gene may not be a candidate for tumor suppressor gene of NB.

PMID- 11526493
TI  - The pVHL-associated SCF ubiquitin ligase complex: molecular genetic analysis of
      elongin B and C, Rbx1 and HIF-1alpha in renal cell carcinoma.
AB  - The VHL gene product (pVHL) forms a multimeric complex with the elongin B and C,
      Cul2 and Rbx1 proteins (VCBCR complex), which is homologous to the SCF family of
      ubiquitin ligase complexes. The VCBCR complex binds HIF-1alpha and HIF-2alpha,
      transcription factors critically involved in cellular responses to hypoxia, and
      targets them for ubiquitin-mediated proteolysis. Germline mutations in the VHL
      gene cause susceptibility to haemangioblastomas, renal cell carcinoma (RCC),
      phaeochromocytoma and other tumours. In addition somatic inactivation of the VHL
      gene occurs in most sporadic clear cell RCC (CC-RCC). However, the absence of
      somatic VHL inactivation in 30-40% of CC-RCC implies the involvement of other
      gatekeeper genes in CC-RCC development. We reasoned that in CC-RCC without VHL
      inactivation, other pVHL-interacting proteins might be defective. To assess the
      role of elongin B/C, Rbx1 and HIF-1alpha in RCC tumorigenesis we (a) mapped the
      genes to chromosomes 8q(cen) (elongin C), 16p13.3 (elongin B) and 22q11.2 (Rbx1)
      by FISH, monochromosomal somatic cell hybrid panel screening and in silico
      GenBank homology searching; (b) determined the genomic organisation of elongin C
      (by direct sequencing of PAC clones), Rbx1 and elongin B (by GenBank homology
      searching); and (c) performed mutation analysis of exons comprising the coding
      regions of elongins B, C and Rbx1 and the oxygen-dependent degradation domain of
      HIF-1alpha by SSCP screening and direct sequencing in 35 sporadic clear cell RCC
      samples without VHL gene inactivation and in 13 individuals with familial non-VHL
      clear cell RCC. No coding region sequence variations were detected for the
      elongin B, elongin C or Rbx1 genes. Two amino acid substitutions (Pro582Ser and
      Ala588Thr) were identified in the oxygen-dependent degradation/pVHL binding
      domain of HIF-1alpha, however neither substitution was observed exclusively in
      tumour samples. Association analysis in panels of CC-RCC and non-neoplastic
      samples using the RFLPs generated by each variant did not reveal allelic
      frequency differences between RCC patients and controls (P>0.32 by chi-squared
      analysis). Nevertheless, the significance of these variations and their potential
      for modulation of HIF-1alpha function merits further investigation in both other
      tumour types and in non-neoplastic disease. Taken together with our previous Cul2
      mutation analysis these data suggest that development of sporadic and familial
      RCC is not commonly contributed to by genetic events altering the destruction
      domain of HIF-1alpha, or components of the HIF-alpha destruction complex other
      than VHL itself. Although (a) activation of HIF could occur through mutation of
      another region of HIF-a, and (b) epigenetic silencing of elongin B/C, Cul2 or
      Rbx1 cannot be excluded, these findings suggest that pVHL may represent the sole
      mutational target through which the VCBR complex is disrupted in CC-RCC. HIF
      response is activated in CC-RCC tumorigenesis.

PMID- 11526495
TI  - Germline SDHD mutation in paraganglioma of the spinal cord.
AB  - Hereditary paraganglioma of the head and neck is associated with germline
      mutations in the SDHD gene, which encodes a mitochondrial respiratory chain
      protein. Paragangliomas of the central nervous system are very rare, occur almost
      exclusively in the cauda equina of the spinal cord and are considered non
      familial. In the present study, we screened 22 apparently sporadic paragangliomas
      of the cauda equina for SDHD mutations. One spinal paraganglioma and similar
      cerebellar tumours that developed 22 years later in the same patient contained a
      missense mutation at codon 12 (GGT-->AGT, Gly-->Ser) and a silent mutation at
      codon 68 (AGC-->AGT, Ser-->Ser). There was no family history of paragangliomas
      but DNA from white blood cells of this patient showed the same sequence
      alterations, indicating the presence of a germline mutation. All other cases of
      spinal paraganglioma had the wild-type SDHD sequence, except one case with a
      silent mutation at codon 68 (AGC-->AGT, Ser-->Ser). This is the first observation
      indicating that inherited SDHD mutations may occasionally cause the development
      of paragangliomas in the central nervous system.

PMID- 11526497
TI  - beta-catenin is a downstream effector of Wnt-mediated tumorigenesis in the
      mammary gland.
AB  - The Wnt signal transduction pathway has been implicated in mammary tumorigenesis
      in the mouse. beta-catenin, a key downstream effector of this pathway interacts
      with and thus activates the Tcf/Lef family of transcription factors. Elevated
      levels of beta-catenin have been found in many human tumors, notably colon
      carcinomas. Recently, elevated levels of beta-catenin have been associated with
      poor prognosis in human adenocarcinoma of the breast. In order to assess the
      possible role of beta-catenin in mammary carcinoma, we have created transgenic
      mice bearing the MMTV-LTR driving an activated form of beta-catenin. These mice
      develop mammary gland hyperplasia and mammary adenocarcinoma, a phenotype very
      similar to that of transgenic mice expressing an MMTV-driven Wnt gene. Indeed,
      the histopathology of the mammary tumors in Wnt-mediated adenocarcinoma is
      identical to that observed in our beta-catenin-mediated disease model.
      Furthermore, putative beta-catenin transcriptional targets, cyclin D1 and c-myc,
      are elevated in beta-catenin-mediated mammary tumors and cell lines. These
      observations support the notion that the oncogenic Wnt pathway operates via beta
      catenin and its targets in the context of mammary hyperplasia and carcinoma.

PMID- 11526496
TI  - The growth-promoting activity of the Bad protein in chicken embryo fibroblasts
      requires binding to protein 14-3-3.
AB  - Phosphorylation of the Bad protein is a key regulatory event in the prevention of
      apoptosis by survival factors. Phosphorylated Bad binds to the cytosolic 14-3-3
      protein and is sequestered from the apoptotic machinery of the mitochondrial
      membrane. To examine the role of Bad in cell growth and apoptosis in primary
      cultures, we produced stable Bad transfectants of chicken embryo fibroblasts
      (CEF). As expected, serum starvation of Bad transfectants promoted apoptosis.
      However, Bad-transfected CEF maintained in media with a high serum concentration
      were capable of anchorage-independent growth and grew to a higher saturation
      density than control CEF transfected with the empty vector. High dilutions of the
      infectious retroviral vector RCAS expressing Bad led to the formation of
      multilayered cell foci. The growth-promoting effects of Bad were dependent on the
      serine 136 phosphorylation site and correlated directly with binding of Bad to 14
      3-3. These results suggest that phosphorylated Bad promotes cell growth and in
      oncogenic transformation may contribute to the neoplastic phenotype of the cell.

PMID- 11526498
TI  - Activation of p53 transcriptional activity requires ATM's kinase domain and
      multiple N-terminal serine residues of p53.
AB  - The ATM protein kinase regulates the cell's response to DNA damage by regulating
      cell cycle checkpoints and DNA repair. ATM phosphorylates several proteins
      involved in the DNA-damage response, including p53. We have examined the
      mechanism by which ATM regulates p53's transcriptional activity. Here, we
      demonstrate that reintroduction of ATM into AT cells restores the activation of
      p53 by the radio-mimetic agent bleomycin. Further, p53 activation is lost when a
      kinase inactive ATM is used, or if the N-terminal of ATM is deleted. In addition,
      AT cells stably expressing ATM showed decreased sensitivity to Ionizing Radiation
      induced cell killing, whereas cells expressing kinase inactive ATM or N
      terminally deleted ATM were indistinguishable from AT cells. Finally, single
      point-mutations of serines 15, 20, 33 or 37 did not individually block the ATM
      dependent activation of p53 transcriptional activity by bleomycin. However,
      double mutations of either serines 15 and 20 or serines 33 and 37 blocked the
      ability of ATM to activate p53. Our results indicate that the N-terminal of ATM
      and ATM's kinase activity are required for activation of p53's transcriptional
      activity and restoration of normal sensitivity to DNA damage. In addition,
      activation of p53 by ATM requires multiple serine residues in p53's
      transactivation domain.

PMID- 11526500
TI  - The rapid destabilization of p53 mRNA in immortal chicken embryo fibroblast
      cells.
AB  - The steady-state levels of p53 mRNA were dramatically lower in immortal chicken
      embryo fibroblast (CEF) cell lines compared to primary CEF cells. In the presence
      of cycloheximide (CHX), the steady-state levels of p53 mRNA markedly increased in
      immortal CEF cell lines, similar to levels found in primary cells. The de novo
      synthetic rates of p53 mRNA were relatively similar in primary and immortal cells
      grown in the presence or absence of CHX. Destabilization of p53 mRNA was observed
      in the nuclei of immortal, but not primary, CEF cells. The half-life of p53 mRNA
      in primary cells was found to be a relatively long 23 h compared to only 3 h in
      immortal cells. The expression of transfected p53 cDNA was inhibited in immortal
      cells, but restored upon CHX treatment. The 5'-region of the p53 mRNA was shown
      to be involved in the rapid p53 mRNA destabilization in immortal cells by
      expression analysis of 5'- and 3'-deleted p53 cDNAs as well as fusion mRNA
      constructs of N-terminal p53 and N-terminal deleted LacZ genes. Together, it is
      suggestive that the downregulation of p53 mRNA in immortal CEF cells occurs
      through a post-transcriptional destabilizing mechanism.

PMID- 11526499
TI  - Acquired expression of transcriptionally active p73 in hepatocellular carcinoma
      cells.
AB  - p53 and p73 proteins activate similar target genes and induce apoptosis and cell
      cycle arrest. However, p53, but not p73 is considered a tumour-suppressor gene.
      Unlike p53, p73 deficiency in mice does not lead to a cancer-prone phenotype, and
      p73 gene is not mutated in human cancers, including hepatocellular carcinoma.
      Here we report that normal liver cells express only DeltaN-p73 transcript forms
      giving rise to the synthesis of N-terminally truncated, transcriptionally
      inactive and dominant negative p73 proteins. In contrast, most hepatocellular
      carcinoma cells express TA-p73 transcript forms encoding full-length and
      transcriptionally active p73 proteins, in addition to DeltaN-p73. We also show
      that together with the acquired expression of TA-p73, the 'retinoblastoma
      pathway' is inactivated, and E2F1-target genes including cyclin E and p14(ARF)
      are activated in hepatocellular carcinoma. However, there was no full correlation
      between 'retinoblastoma pathway' inactivation and TA-p73 expression. Most TA-p73
      expressing hepatocellular carcinoma cells have also lost p53 function either by
      lack of expression or missense mutations. The p73 gene, encoding only DeltaN-p73
      protein, may function as a tumour promoter rather than a tumour suppressor in
      liver tissue. This may be one reason why p73 is not a mutation target in
      hepatocellular carcinoma.

PMID- 11526501
TI  - E2F2 converts reversibly differentiated PC12 cells to an irreversible,
      neurotrophin-dependent state.
AB  - E2Fs play a central role in cell proliferation and growth arrest through their
      ability to regulate genes involved in cell cycle progression, arrest and
      apoptosis. Recent studies further indicate that this family of transcriptional
      regulators participate in cell fate/differentiation events. They are thus likely
      to have a prominent role in controlling the terminal differentiation process and
      its irreversibility. Here we have specifically examined the role of E2F2 in
      neuronal differentiation using a gain-of-function approach. Endogenous E2F2
      increased in PC12 cells in response to nerve growth factor (NGF) and was also
      expressed in cerebellar granule neurons undergoing terminal differentiation.
      While PC12 cells normally undergo reversible dedifferentiation and cell cycle re
      entry upon NGF removal, forced expression of E2F2 inhibited these events and
      induced apoptosis. Thus, E2F2 converted PC12-derived neurons from a reversible to
      a 'terminally' differentiated, NGF-dependent state, analogous to postmitotic
      sympathetic neurons. This contrasts with the effects of E2F4, which enhances the
      differentiation state of PC12 cells without affecting cell cycle parameters or
      survival. These results indicate that E2F2 may have a unique role in maintaining
      the postmitotic state of terminally differentiated neurons, and may participate
      in apoptosis in neurons attempting to re-enter the cell cycle. It may also be
      potentially useful in promoting the terminally arrested/differentiated state of
      tumor cells.

PMID- 11526502
TI  - Functional cooperation between JunD and NF-kappaB in rat hepatocytes.
AB  - AP-1 and NF-kappaB are rapidly activated during liver regeneration. Whether these
      parallel inductions have potential functional implications is not known. Isolated
      rat hepatocytes were stimulated with two mitogens, epidermal growth factor or
      hepatocyte growth factor and with tumor necrosis factor alpha, a cytokine
      involved in the liver regenerative response in vivo and a strong inducer of NF
      kappaB. All three cytokines increased AP-1 and NF-kappaB binding to their cognate
      cis-element and induced a 2.5-fold activation of NF-kappaB-dependent
      transcription. Inactivation of AP-1 by TAM67, a dominant negative mutant of AP-1
      drastically inhibited basal and cytokine-induced NF-kappaB transactivation.
      Overexpression of Jun D, but not of the other Jun or Fos proteins increased by
      threefold NF-kappaB transactivation. Functional cooperation between JunD and p65
      was demonstrated in a simple Gal-hybrid system. Finally, a twofold decrease in NF
      kappaB transactivation was found in hepatocytes isolated from JunD(-/-) mice
      compared with hepatocytes from JunD(+/+) mice. Altogether these data demonstrate
      a functional cooperation of p65 with JunD, a major constituent of AP-1 in normal
      hepatocytes.

PMID- 11526503
TI  - Involvement of protein kinase Cdelta in contact-dependent inhibition of growth in
      human and murine fibroblasts.
AB  - There is evidence that protein kinase C delta (PKCdelta) is a tumor suppressor,
      although its physiological role has not been elucidated so far. Since important
      anti-proliferative signals are mediated by cell-cell contacts we studied whether
      PKCdelta is involved in contact-dependent inhibition of growth in human (FH109)
      and murine (NIH3T3) fibroblasts. Cell-cell contacts were imitated by the addition
      of glutardialdehyde-fixed cells to sparsely seeded fibroblasts. Downregulation of
      the PKC isoforms alpha, delta, epsilon, and mu after prolonged treatment with 12
      O-tetradecanoylphorbol-13-acetate (TPA, 0.1 microM) resulted in a significant
      release from contact-inhibition in FH109 cells. Bryostatin 1 selectively
      prevented TPA-induced PKCdelta-downregulation and reversed TPA-induced release
      from contact-inhibition arguing for a role of PKCdelta in contact-inhibition. In
      accordance, the PKCdelta specific inhibitor Rottlerin (1 microM) totally
      abolished contact-inhibition. Interestingly, immunofluorescence revealed a rapid
      translocation of PKCdelta to the nucleus when cultures reached confluence with a
      peak in early-mid G1 phase. Nuclear translocation of PKCdelta in response to cell
      cell contacts could also be demonstrated after subcellular fractionation by
      Western blotting and by measuring PKCdelta-activity after immunoprecipitation.
      Transient transfection of NIH3T3 cells with a dominant negative mutant of
      PKCdelta induced a transformed phenotype. We conclude that PKCdelta is involved
      in contact-dependent inhibition of growth.

PMID- 11526504
TI  - hH-Rev107, a class II tumor suppressor gene, is expressed by post-meiotic
      testicular germ cells and CIS cells but not by human testicular germ cell tumors.
AB  - By systematic analysis of a human testis library, we have isolated the hH-Rev107
      3 cDNA, identical to hH-Rev107-1 cDNA, which was previously described as a class
      II tumor suppressor gene. In this study, two transcripts (1 and 0.8 kb) were
      detected by Northern blot in all human tissues, excepted in thymus. The strongest
      expression was found in testis, skeletal muscle and heart. These two mRNA are
      probably transcribed from only one gene that we mapped to the q12-q13 region of
      the chromosome 11. In human testis, hH-Rev107 gene expression was localized, by
      in situ hybridization, within the round spermatids. To investigate a possible
      role for hH-Rev107 protein in testicular malignant growth, we examined the
      expression of this gene in germ cell tumors. A strong hH-Rev107 gene expression
      was observed in normal testis as well as in samples with preinvasive carcinoma in
      situ but was completely absent in overt tumors, both seminomas and non-seminomas.
      By in situ hybridization, CIS was found hH-Rev107 positive and tumor negative. A
      semi-quantitative assessment of hH-Rev107 mRNA level in testicular germ cell
      tumors, by RT-PCR, exhibited a ninefold decrease in the gene expression. No gross
      structural aberrations of hH-Rev107 gene were detected in these human primary
      tumors. The results suggest that down-regulation of hH-Rev107 may be associated
      with invasive progression of testicular germ cell tumors.

PMID- 11526505
TI  - Role of cyclic AMP responsive element in the UVB induction of cyclooxygenase-2
      transcription in human keratinocytes.
AB  - It has been shown that UVB irradiation induces expression of COX-2 and up
      regulation of COX-2 plays a functional role in UVB tumor promotion. In this
      study, we examined the cis-elements in the human COX-2 promoter that may be
      responsible for the UVB induction of COX-2. Analyses with the COX-2 promoter
      region revealed that the cyclic AMP responsive element near the TATA box was
      essential for both basal and UVB induced COX-2 expression. This was further
      supported by studies using a dominant negative mutant of CREB, which strongly
      inhibited the activity of COX-2 promoter. Electrophoretic mobility shift assays
      indicated that CREB and ATF-1 were the major proteins binding to the COX-2 CRE.
      CREB and ATF-1 were phosphorylated upon UVB treatment, and SB202190, a p38 MAPK
      inhibitor, decreased the phosphorylation of CREB/ATF-1 and suppressed COX-2
      promoter activity. In contrast, treatment with forskolin, an activator of
      adenylyl cyclase, led to phosphorylation of CREB and ATF-1 and activation of COX
      2 promoter. Finally, enhanced binding of phospho-CREB/ATF-1 to the COX-2 CRE was
      observed after UVB induction. Thus, one signaling pathway for UVB induction of
      human COX-2 involves activation of p38, subsequent phosphorylation of CREB/ATF-1,
      and activation of the COX-2 CRE through enhanced binding of phosphorylated
      CREB/ATF-1.

PMID- 11526506
TI  - Molecular mechanisms for aberrant expression of the human breast cancer specific
      gene 1 in breast cancer cells: control of transcription by DNA methylation and
      intronic sequences.
AB  - Breast cancer specific gene 1 (BCSG1), also referred as synuclein gamma, is the
      third member of a neuronal protein family synuclein. BCSG1 is not expressed in
      normal breast tissues but highly expressed in advanced infiltrating breast
      carcinomas. When over expressed, BCSG1 significantly stimulates breast cancer
      metastasis. To elucidate the molecular mechanisms underlying the abnormal
      transcription of BCSG1 in breast cancer cells, in this study, we isolated a 2195
      base pair fragment of human BCSG1 gene. This fragment includes 1 kb 5'-flanking
      region, exon 1, and intron 1. By analysing the promoter activity and the
      methylation status of the exon 1 region, we show that (1) Intron 1 plays critical
      roles in the control of BCSG1 gene transcription through cis-regulatory sequences
      that affect BCSG1 transcription in cell type-specific and cell type-nonspecific
      manners. (2) The activator protein-1 (AP-1) is functionally involved in BCSG1
      transcription in breast cancer cells through its binding to an AP-1 motif located
      in the intron 1. (3) The exon 1 region of BCSG1 gene contains a CpG island that
      is unmethylated in BCSG1-positive SKBR-3 and T47D cells but densely methylated in
      BCSG1-negative MCF-7 cells. (4) Treating MCF-7 cells with a demethylating agent 5
      Aza-2'-deoxycytidine specifically activated BCSG1 transcription. Thus, our
      results suggest that while the cellular content of transcription activators and
      repressors that interact with the cis-regulatory sequences present in the intron
      1 contribute prominently to the tissue-specific expression of BCSG1,
      demethylation of exon 1 is an important factor responsible for the aberrant
      expression of BCSG1 in breast carcinomas.

PMID- 11526507
TI  - A repertoire library that allows the selection of synthetic SH2s with altered
      binding specificities.
AB  - Tyrosine phosphorylation is one of the major mechanisms involved in the
      intracellular propagation of external signals. Strategies aimed at interfering
      with this process might allow the control of several cellular phenotypes. SH2
      domains mediate protein-protein interactions by recognizing phosphotyrosine (pY)
      residues in the context of specific phosphopeptides. We created an SH2-scaffolded
      repertoire library by randomly mutagenizing five critical amino acid positions in
      the specificity-determining region of the PLCgamma C-terminal SH2 domain.
      Synthetic SH2 domains were selected from the library using biotinylated
      phosphopeptides derived from a natural PLCgamma-SH2 ligand as well as unrelated
      SH2 ligands. The isolated SH2s displayed high binding affinity constants for the
      selecting peptides and were capable of interacting with the corresponding
      proteins.

PMID- 11526509
TI  - Expression of herstatin, an autoinhibitor of HER-2/neu, inhibits transactivation
      of HER-3 by HER-2 and blocks EGF activation of the EGF receptor.
AB  - The four members of the EGF receptor family are capable of homomeric as well as
      heteromeric interactions. HER-2/neu (erbB-2) dominates as the preferred
      coreceptor that amplifies mitogenic signaling. An alternative HER-2/neu product,
      herstatin, consists of a segment of the ectodomain of p185HER-2 and an intron
      encoded C-terminus. Recombinant herstatin was found to bind with nM affinity and
      inhibit p185HER-2. To further examine the impact on receptor activity, herstatin
      was expressed with various receptor tyrosine kinases. In CHO cells that
      overexpressed HER-2, herstatin caused a sevenfold inhibition of colony formation
      that corresponded to a reduction in the tyrosine phosphorylation of p185HER-2.
      Herstatin also prevented HER-2 mediated transactivation of the kinase impaired
      HER-3 as reflected in transphosphorylation of HER-3 and heteromers between HER-2
      and HER-3. In EGF receptor-overexpressing cells, EGF induction of receptor
      dimerization and tyrosine phosphorylation were reduced more than 90%, and
      receptor down-regulation as well as colony formation were also suppressed by
      coexpression with herstatin. Inhibition was selective for the EGF receptor family
      since herstatin expression did not reduce tyrosine phosphorylation mediated by
      the FGF receptor-2 or by insulin-like growth factor -1. Herstatin bound to the
      EGF receptor as well as to p185HER-2 in pull-down assays suggesting that complex
      formation may be involved in receptor inhibition. Our findings indicate that
      herstatin has the capability to negatively regulate combinations of interactions
      between group I receptor tyrosine kinases that confer synergistic growth signals.

PMID- 11526508
TI  - Mitochondrial mutations in early stage prostate cancer and bodily fluids.
AB  - We recently demonstrated the existence of specific patterns of somatic
      mitochondrial DNA (mtDNA) mutations in several cancers. Here we sought to
      identify the presence of mtDNA mutations in prostate cancer and their paired PIN
      lesions. The D-loop region, 16S rRNA, and the NADH subunits of complex I were
      sequenced to identify mtDNA mutations in 16 matched PIN lesions and primary
      prostate cancers. Twenty mtDNA mutations were detected in the tumor tissue of
      three patients. Identical mutations were also identified in the PIN lesion from
      one patient. This patient with multiple point mutations also harbored a high
      frequency of microsatellite instability (MSI-H) in nuclear mononucleotide repeat
      markers. Remarkably, identical mutations were also detected in all (3/3) matched
      urine and plasma samples obtained from these patients. Although mitochondrial
      mutations are less common in prostate adenocarcinoma, they occur early in cancer
      progression and they can be detected in bodily fluids of early stage disease
      patients. The identification of MtDNA mutations may complement other early
      detection approaches for prostate cancer.

PMID- 11526510
TI  - Regulation of Laloo by the Xenopus C-terminal Src kinase (Xcsk) during early
      vertebrate development.
AB  - Mesoderm formation in the frog, Xenopus laevis, is dependent on the activity of
      one or more members of the Src family kinases; the molecular interactions
      underlying this requirement are not well understood. The C-terminal Src Kinase
      (Csk) is a potent inhibitor of Src activity, and is required for normal mammalian
      development; here we report the characterization of Xenopus Csk (Xcsk). Xcsk is
      widely expressed during early development, physically interacts with the Src
      kinase Laloo, and inhibits the generation of mesoderm by the Src kinases. Xcsk
      activity requires a functional kinase domain; furthermore, a kinase-inactive Xcsk
      mutant potently synergizes with Laloo during early vertebrate development,
      suggesting a fundamental role for the Src kinase-Csk regulatory circuit during
      mesoderm induction, in vivo.

PMID- 11526511
TI  - Alterations of repeated sequences in 5' upstream and coding regions in colorectal
      tumors from patients with hereditary nonpolyposis colorectal cancer and Turcot
      syndrome.
AB  - One of the characteristics of tumors from patients with germline mutations of DNA
      mismatch repair genes is instability at microsatellite regions (MSI). We analysed
      alterations at repeated sequences of coding regions, as well as those of 5'
      upstream regions, in 29 MSI-High colorectal tumors from patients with hereditary
      nonpolyposis colorectal cancer (HNPCC) and Turcot syndrome. We found that
      repeated sequences in 5' upstream regions were altered in these tumors, at
      considerable frequencies. The (A)10 repeat in the promoter region (position -178
      to approximately -169) of the GAPDH gene was altered in 17% of the tumors. The
      (A)10(TA)9 in the 5' upstream region (position -318 to approximately -291) of the
      mitochondrial isoleucyl tRNA synthetase gene (IleRS-A), coded in nuclear DNA, was
      altered in 59% of the tumors, whereas (A)9 in the 5' upstream region (position 
      859 to approximately -851) of cytoplasmic isoleucyl tRNA synthetase gene (IleRS
      B) was not altered. Alteration at repeated sequences in the coding regions were
      72% at TGFbetaRII(A)10, 24% at IGFIIR(G)8, 45% at BAX(G)8, 55% at E2F4(CAG)13,
      66% at caspase-5 (A)10, 31% at MBD4(A)10, 55% at hMSH3(A)8 and 34% at hMSH6(C)8.
      The number of altered genes increased with the advancement of carcinoma according
      to Dukes categories: mean numbers of altered genes within these 10 genes were 2.6
      for Dukes A, 4.7 for Dukes B and 7.8 for Dukes C. The mean number for adenomas
      was 2.0. These results suggest that the MSI phenotype also causes alteration of
      5' upstream regions which may affect apoptosis and some mitochondrial functions
      in HNPCC and Turcot tumors, and that accumulation of altered genes with repeated
      sequences is associated with the progression of HNPCC and Turcot colorectal
      tumors.

PMID- 11526512
TI  - An extracellular ligand increases the specific activity of the receptor-like
      protein tyrosine phosphatase DEP-1.
AB  - Cellular growth, differentiation and migration is regulated by protein tyrosine
      phosphorylation. Receptor-like protein tyrosine phosphatases are thus likely to
      be key regulators of vital cellular processes. The regulation of these enzymes is
      in general poorly understood. Ligands have been identified only for a small
      subset of the receptor-like protein tyrosine phosphatases and in no case has
      upregulation of the specific activity by extracellular ligands been demonstrated.
      Prompted by earlier findings of ligands for receptor-like protein tyrosine
      phosphatases in extracellular matrix we investigated if Matrigel, a preparation
      of extracellular matrix proteins, contained modulators of the specific activity
      of the receptor-like protein tyrosine phosphatase DEP-1. Matrigel stimulation of
      cells increased the specific activity of immunoprecipitated DEP-1. Also,
      incubation of immunoprecipitated DEP-1 with Matrigel led to an increase in DEP-1
      activity, which was blocked by soluble DEP-1 extracellular domain. Finally,
      immunoprecipitated DeltaECD-DEP-1, a mutant form of DEP-1 lacking most of the
      extracellular domain, failed to respond to Matrigel stimulation. These
      experiments identify Matrigel as a source of DEP-1 agonist(s) and provide the
      first evidence for upregulation of the specific activity of receptor-like protein
      tyrosine phosphatases by extracellular ligands.

PMID- 11526513
TI  - Accelerated degradation of cellular FLIP protein through the ubiquitin-proteasome
      pathway in p53-mediated apoptosis of human cancer cells.
AB  - Apoptosis is a morphologically distinct form of programmed cell death that plays
      a major role in cancer treatments. This cellular suicide program is known to be
      regulated by many different signals from both intracellular and extracellular
      stimuli. Here we report that p53 suppressed expression of the cellular FLICE
      inhibitory protein (FLIP) that potentially blocks apoptotic signaling in human
      colon cancer cell lines expressing mutated and wild-type p53. In contrast, the
      expression of the death receptor KILLER/DR5 (TRAIL-R2) had no effect on FLIP
      expression, although exogenous p53 is known to induce KILLER/DR5 expression. In
      line with these observations, FLIP-negative cancer cells were sensitive to both
      p53- and KILLER/DR5-mediated apoptosis, whereas cells containing high levels of
      FLIP underwent apoptotic cell death when triggered by ectopic p53 expression but
      not by KILLER/DR5 expression. Treating the cells with a specific inhibitor of the
      proteasome inhibited the decrease of FLIP by p53, suggesting that p53 enhances
      the degradation of FLIP via a ubiquitin-proteasome pathway. Thus, the data
      indicate that p53-mediated downregulation of FLIP may explain the potent
      sensitization of human cancer cells to the apoptotic suicide program induced by
      wild-type p53 gene transfer.

PMID- 11526514
TI  - Identification of homozygous deletions at chromosome 16q23 in aflatoxin B1
      exposed hepatocellular carcinoma.
AB  - Loss of heterozygosity (LOH) represents the most frequent genetic alteration
      observed in hepatocellular carcinoma (HCC). Chromosome 16q is of particular
      interest as it exhibits LOH in 29% of HCC tumors and is frequently lost in
      breast, prostate, ovarian and gastric carcinomas. We genotyped 157 HCC tumors for
      17 microsatellite markers distributed on chromosome 16q and determined a common
      region of LOH localized between the markers D16S518 and D16S504. By refining the
      boundaries of two interstitial LOH and two homozygous deletions, the critical
      region was delimited to 180 kb between D16S3096 and D16S3029. This region is
      located in intron 8 of the WWOX/FOR gene, but a search for mutations in all
      coding exons of this gene in 27 HCC tumors and cell lines did not reveal any
      tumor somatic alterations. Furthermore, by RT-PCR, no abnormal transcripts of
      this WWOX/FOR gene was detected in nine HCC cell lines. Finally, analysis of the
      p53 gene mutations with the clinical parameters of all tumors revealed that the
      two homozygous deletions have occurred in tumors presenting a R249S mutation. Our
      data revealed a relationship between chromosome 16q homozygous deletions and
      R249S p53 mutations in tumors where the patient had been exposed to aflatoxin B1
      (P=0.002). These results are consistent with a role of aflatoxin B1 in the
      instability of chromosome 16q at the fragile site FRA16D. However, the nature of
      the specific gene that is altered during hepatocarcinogenesis remains to be
      elucidated.

PMID- 11526516
TI  - Genetic loci controlling susceptibility to gamma-ray-induced thymic lymphoma.
AB  - BALB/c is a susceptible strain for the development of gamma-ray induced mouse
      thymic lymphoma whereas MSM shows resistance. Association analysis of 220
      backcross mice between the two strains using 67 markers was carried out to
      identify loci involved in the control of susceptibility. The genotype of mice
      with lymphoma showed excess heterozygosity relative to MSM homozygosity at
      D2Mit15 and D4Mit12 and was skewed toward MSM-derived alleles at D5Mit5. The P
      values in Mantel-Cox test were 0.0048 (D2Mit15), 0.0034 (D4Mit12) and 0.0048
      (D5Mit5), suggesting association at the three loci in the susceptibility.
      Cooperative effect on lymphomagenesis was also observed among the three loci. To
      obtain independent evidence for linkage at D4Mit12, we made partially congenic
      mice in which a D4Mit12 region in BALB/c was replaced by MSM-derived homolog.
      Examination for the lymphoma susceptibility in 78 progeny of the congenic mice
      confirmed the effect of the locus near D4Mit12 (P=0.0037). The result, together
      with the linkage analysis, shows that the locus near D4Mit12 is regarded as a
      confirmed linkage but the other two loci as marginally suggestive.

PMID- 11526515
TI  - Birt-Hogg-Dube syndrome: mapping of a novel hereditary neoplasia gene to
      chromosome 17p12-q11.2.
AB  - Birt-Hogg-Dube syndrome (BHD) is an autosomal dominant neoplasia syndrome
      characterized mainly by benign skin tumors, and to a lesser extent, renal tumors
      and spontaneous pneumothorax. To map the BHD locus, we performed a genome-wide
      linkage analysis using polymorphic microsatellite markers on a large Swedish BHD
      family. Evidence of linkage was identified on chromosome 17p12-q11.2, with a
      maximum LOD score of 3.58 for marker D17S1852. Further haplotype analysis defined
      a approximately 35 cM candidate interval between the two flanking markers,
      D17S1791 and D17S798. This information will facilitate the identification of the
      BHD gene, leading to the understanding of its underlying molecular etiology.

PMID- 11526517
TI  - Allergic contact dermatitis from natural latex.
AB  - BACKGROUND: Reports on natural latex allergy have increased steadily during the
      last 10 years. Latex allergy generally refers to a type 1 reaction to natural
      rubber latex (NRL) proteins with clinical manifestations ranging from contact
      urticaria to asthma and anaphylaxis. Previous United States studies on NRL
      allergy largely have been reported by allergists with little detailed information
      on hand eczema, contact allergy, or on outcome. The present study was performed
      from March 1998 to November 1999 with the aim of finding out the prevalence of
      type IV hypersensitivity to latex in patients with suspected rubber allergy.
      MATERIALS AND METHODS: A total of 167 patients with hand eczema and contact with
      rubber products underwent patch testing with the standard screening and rubber
      components (test series Deutsche Kontaktallergiegruppe), and NRL pure provided by
      Regent (liquid high ammonia 0.7% NRL, accelerator, and preservative-free latex)
      between March 1998 and November 1999. The charts of all NRL positive patients are
      reported with the results of history, prick, patch tests, total IgE, specific IgE
      to latex (FEIA) test and follow-up data (after 6 months). RESULTS: Four patients
      (3 men) showed positive patch test results to NRL. One of these patients also
      reacted to the rubber chemical tetraethylthiuram monosulfide, and another one of
      these patients revealed a type 1 reaction to NRL, diagnosed by positive reaction
      to prick test. The other 3 patients with patch test reactions to NRL had negative
      reactions to prick tests to NRL extracts after 20 minutes. All 4 patients had a
      positive delayed prick test reaction to NRL. Latex FEIA test result was negative
      in all 4 patients. The contact eczema healed after elimination of the latex
      gloves and medical latex devices in all patients. Furthermore, 10 of the 167
      patch testing patients (6%) were positive for tetramethylthiuram monosulfide 1%.
      CONCLUSION: In the present study with 167 patients, the prevalence of type IV
      hypersensitivity to latex was 2.4%. We recommend that the patch test with NRL as
      well as with rubber additives should be performed in patients of suspected
      contact dermatitis caused by rubber products.

PMID- 11526518
TI  - Prevalence of evaluation for latex allergy and association with practice
      characteristics in United States dermatologists: results of a cross-sectional
      survey.
AB  - BACKGROUND: Natural rubber latex allergy is a potentially life-threatening,
      immunoglobin E (IgE) mediated reaction. Despite great strides in identification
      of high-risk groups, methods for diagnosis remain limited in the United States
      and most evaluations are performed by allergists. OBJECTIVE: The objective of
      this study was to estimate the prevalence of evaluation for latex allergy and
      association with practice characteristics in United States dermatologists.
      METHODS: A cross-sectional survey of one third of United States Fellows of the
      American Academy of Dermatology. RESULTS: The survey response rate was 43%. Of
      responding dermatologists, 17% stated that they evaluate patients for latex
      allergy, most commonly with a radioallergosorbent (RAST) or use test. Only 3.6%
      stated that they perform prick or scratch tests for latex allergy in their
      office, and most of these dermatologists (86%) prepare their own latex prick test
      solutions. Evaluation for latex allergy was significantly associated with patch
      testing, photopatch testing, an interest in contact dermatitis, and number of
      contact dermatitis books owned, but not with number of years in practice.
      CONCLUSIONS: Most United States dermatologists do not evaluate patients for latex
      allergy, most likely because of lack of available antigens and because methods
      for diagnosing latex allergy are not familiar to most dermatologists.

PMID- 11526519
TI  - Dental metal allergy in patients with oral, cutaneous, and genital lichenoid
      reactions.
AB  - BACKGROUND: The subject of lichen planus (LP) and dental metal allergy long has
      been debated. An overwhelming majority of the existing literature focuses on
      mercury and gold salts in relation to oral lichen planus. OBJECTIVE: Our
      objective was to expand current knowledge regarding LP and lichenoid lesions (LL)
      and dental metal allergy by investigating more metals and investigating cutaneous
      and genital disease in addition to oral disease. METHODS: Fifty-one patients with
      known LP or LL were patch tested to a series of dental metals. Patients chose to
      replace their dental metals or make no revision. A telephone survey was conducted
      after 1 year to determine disease state. RESULTS: Thirty-eight of 51 patients
      (74.5%) had at least 1 positive reaction. Twenty-five of 51 patients (49.0%)
      showed sensitivity to at least 1 mercurial allergen. Prevalence data for patients
      patch tested by the North American Contact Dermatitis Group (NACDG) from 1996 to
      1998 was available for chromate, cobalt, gold, nickel, and thimerosal. The
      prevalence of positive reactions was higher in our group than in the NACDG group
      for all 5 of these allergens, and statistical significance was achieved for
      chromate (P = .028), gold (P = .041), and thimerosal (P = .005). Of patients who
      had a positive patch test reaction to 1 or more metals, 100% (9 of 9) reported
      improvement after metal replacement, whereas 62.5% (15 of 24) reported
      improvement without metal replacement. CONCLUSION: Sensitization to dental metals
      is more common among LP and LL patients than in routinely tested patients, and
      might be an etiologic or triggering factor in the disease.

PMID- 11526520
TI  - Role of body piercing in the induction of metal allergies.
AB  - BACKGROUND: Metal allergies have been linked to body piercing in women, but few
      studies have explored this phenomenon in men. It has been postulated that
      nickel/cobalt and nickel/palladium exhibit coreactivity in patients allergic to
      metals. OBJECTIVES: (1) Determine the incidence rate and the source for the
      induction of metal allergy in 3 groups of men: unpierced, one site-pierced, and
      multiple sites-pierced; and (2) evaluate the degree of coreactivity between
      nickel/cobalt and nickel/palladium. METHODS: Men aged 18 to 43 years (n = 118)
      were patch-tested using the North American Contact Dermatitis Group's protocol to
      nickel sulfate 2.5%, gold sodium thiosulfate 0.5%, cobalt chloride 1%, and
      palladium chloride 1%. RESULTS: Eleven (9.3%) subjects had at least 1 positive
      reaction. When characterized by the number of pierced sites, positive reactions
      were seen in 2 of 50 (4.0%) unpierced, 3 of 27 (11.1%) one site-pierced, and 6 of
      41 (14.6%) multiply pierced men. The number of piercings was a statistically
      significant predictor of metal allergy (P = .04). Four (66.7%) cobalt and no
      palladium reactions occurred in nickel-positive subjects. The source for the
      induction of the allergic response was primarily jewelry, which accounted for 5
      of 6 nickel allergies and 2 of 3 gold allergies. Silver jewelry was a significant
      predictor of an allergic response. CONCLUSION: This study represents the first
      report that the number of body piercings has positive bearing on the incidence of
      metal allergy in men. The data also support the theory of coreactivity for
      nickel/cobalt, but not for nickel/palladium.

PMID- 11526521
TI  - Contact allergenic potency: correlation of human and local lymph node assay data.
AB  - BACKGROUND: Effective toxicologic evaluation of skin sensitization requires that
      potential contact allergens are identified and that the likely risks of
      sensitization among exposed populations are assessed. By definition, chemicals
      that are classified as contact sensitizers have the capacity to cause allergic
      contact dermatitis (ACD) in humans. However, this hazard is not an all-or-nothing
      phenomenon; clear dose-response relationships can be discerned and thresholds
      identified for both the induction of sensitization and the elicitation of ACD.
      Commonly, these parameters are grouped under the heading of potency, the
      determination of which is vital for risk assessment. Preclinical testing for
      sensitization potential is critically important for hazard assessment before
      human exposure. The murine local lymph node assay (LLNA) is the most recently
      accepted test method for sensitization hazard assessment. OBJECTIVE: The aim was
      to compare potency estimations derived from LLNA data with clinical
      determinations of relative potency based on human data. METHODS: No-effect levels
      (NOELs) for a range of 21 chemicals were determined from nondiagnostic human
      repeat patch test studies as reported in the literature. These levels were
      compared with LLNA EC(3) values, the estimated concentration required to produce
      a 3-fold increase (positive response) in draining lymph node cell (LNC)
      proliferative activity. RESULTS: Using available human repeat patch test data,
      together with expert judgment, the compounds were classified as strong, moderate,
      weak, extremely weak, or nonsensitizing. Additionally, the potency of each
      chemical was classified independently based on its LLNA EC(3) value. The results
      show clearly that LLNA EC(3) values are very comparable with the NOELs calculated
      from the literature. Moreover, the potency rankings based upon LLNA EC(3) data
      support their human classification. CONCLUSION: The present investigations show
      that the LLNA can be used to provide quantitative estimates of relative skin
      sensitizing potency EC(3) values that correlate closely with NOELs established
      from human repeat patch testing and from our clinical experience.

PMID- 11526522
TI  - Rapid allergen delivery with photomechanical waves for inducing allergic skin
      reactions in the hairless guinea pig animal model.
AB  - BACKGROUND: Patch testing is the confirmatory procedure for allergic contact
      dermatitis. The test requires the application of chemicals under occlusion for
      approximately 48 hours to maximize penetration, although it can also produce
      irritation. Photomechanical waves (PW) have been shown to render the stratum
      corneum transiently permeable and facilitate the delivery of macromolecules into
      the epidermis. This alternative might reduce prolonged occlusion of the skin to
      minimize irritancy, while retaining the sensitivity of the test. OBJECTIVE: PW
      was used to facilitate the delivery of an allergen into the skin in vivo.
      METHODS: The allergic skin reaction using PW delivery was compared with 5-minute
      and 21-hour occlusion in a sensitized hairless albino guinea pig model. The pigs
      were sensitized by intradermal injection of (0.01%) dinitrochlorobenzene (DNCB)
      and topical administration (0.1%, 1 week later) of the hapten. One month later,
      testing for the allergic response was performed by the administration with PW of
      10 microL of 0.1% DNCB. RESULTS: Our results show that there was an allergic
      reaction for the 24 hour occlusion or PW delivery of the antigen. In contrast, no
      response was observed for the 5-minute occlusion with the antigen. CONCLUSION:
      The rapid delivery of antigens with PW can improve the test for the diagnosis of
      contact dermatitis.

PMID- 11526523
TI  - Strategy to decrease the risk of adverse effects of fragrance ingredients in
      cosmetic products.
AB  - In spite of extensive self-regulation of the fragrance industry, fragrance
      ingredients are still major causes of allergic contact dermatitis. There are
      indications that the problem is increasing in some countries, and that many
      nonregulated compounds are involved in the development of allergies. The use of
      essential oils in fragrance compounds might add both allergenic and carcinogenic
      compounds to a product and the exact composition of such ingredients is difficult
      to control. Herein, we propose a simple strategy to decrease the risk of adverse
      effects of fragrance ingredients in cosmetic products. This strategy consists of
      four major steps: (1) limit the concentration of fragrance compound in the
      products, (2) follow legislation and guidelines, (3) limit the concentration of a
      number of well-known sensitizing fragrance chemicals, and (4) limit the
      concentration of essential oils and materials with unknown composition. The
      strategy is discussed as an alternative to animal testing and in relation to
      other more resource-demanding approaches to the same problem.

PMID- 11526524
TI  - Patch testing with serial dilutions of budesonide, its R and S diastereomers, and
      potentially cross-reacting substances.
AB  - BACKGROUND: Budesonide, a marker for corticosteroid allergy, is a 1:1 mixture of
      2 diastereomers, the R and S, present in all commercial formulations. Budesonide
      is said to cross-react with group B substances through the R and S diastereomer
      and some group D substances only through the S diastereomer. OBJECTIVE: To
      investigate the cross-reactivity pattern between the R and S diastereomers and 4
      potentially cross-reacting substances, 2 from group B and 2 from group D.
      METHODS: By patch testing 10 patients hypersensitive to budesonide with a serial
      dilution of budesonide, the R and S diastereomer, triamcinolone acetonide,
      amcinonide, prednicarbate, and hydrocortisone-17-butyrate. RESULTS: Nine of 10
      patients reacted to budesonide and the S diastereomer. Seven of 9 to the R
      diastereomer. Each of the 9 patients with S diastereomer allergy reacted to the
      group B and/or group D substances. Five patients reacted to triamcinolone
      acetonide, not to 1.0% but only to 0.0010% and 0.00010%. CONCLUSION: The R and S
      diastereomers can induce positive patch test reactions in budesonide
      hypersensitive individuals. The potential of budesonide to cross-react with
      substances from group B and D might be explained by the presence of the 2
      diastereomers. When patch testing with triamcinolone acetonide, much lower
      concentrations than recommended should be used.

PMID- 11526525
TI  - Allergic contact dermatitis to proparacaine with subsequent cross-sensitization
      to tetracaine from ophthalmic preparations.
AB  - We report 2 cases of allergic contact dermatitis (ACD) to proparacaine and
      tetracaine. Patient 1 is an ophthalmologist with chronic finger pad dermatitis
      sensitized to the topical anesthetic proparacaine. Despite discontinuance of
      proparacaine and substitution with a patch test negative agent, tetracaine, his
      hand dermatitis persisted. Follow up patch testing documented that acquisition of
      contact allergy to tetracaine as well as thiuram had taken place. Patient 2 had a
      periocular eczematous dermatitis with ACD to both proparacaine and tetracaine.
      Cross sensitization between related topical ophthalmologic anesthetics has been
      suggested to be a rare occurrence. We suggest that allergic sensitization and
      possible cross-reaction to topical anesthetics in ophthalmologists and
      ophthalmologic technicians is an occupational hazard. Chronically eczematized
      skin might result in increased exposure to contact allergens and result in
      concomitant allergic sensitization. ACD to topical anesthetic agents among
      ophthalmologists should be recognized as a potential hazard.

PMID- 11526526
TI  - Photocontact dermatitis to ketoprofen.
AB  - A case of photocontact dermatitis from ketoprofen is described in a 19-year-old
      woman with a 3-day history of pruritic lesions on the right forearm. Physical
      examination revealed a 105 x 46 mm, dark reddish lesion consisting of edematous
      erythema and papules on the extensor aspect of the right forearm. In photopatch
      testing, positive reactions to as-is (Mohrus compress [Hisamitsu Pharmaceutical
      Co, Inc, Tosu, Japan]), ketorofen 1% in petrolatum (pet.), suprofen 1% pet., and
      tiaprofenic acid 1% pet. were seen. We must consider the anatomic sites on which
      nonsteroidal anti-inflammation medicaments are applied, as well as their effects.

PMID- 11526527
TI  - Occupational contact urticaria and late-phase bronchial asthma caused by
      compositae pollen in a florist.
AB  - Insect-pollinated members of the plant family Compositae (Asteraceae) rarely
      cause immediate-type hypersensitivity disease; however, this may have quite
      disabling consequences, which is shown by the case of a 42-year-old female
      florist. She developed contact urticaria later accompanied by rhinoconjunctivitis
      and bronchial asthma with maximum obstruction occurring some hours after the end
      of occupational exposure to the causative Compositae pollens of, for example,
      dandelions, blazing star, golden rod, yarrow, Aster ssp, chrysanthemums, and
      marguerite. Skin testing revealed immediate-type hypersensitivity to several
      members of the above-mentioned plant family confirmed by demonstration of
      specific IgE antibodies. Bronchial provocation testing yielded a positive
      response with all 4 pollen extracts tested. The patient had to give up work in a
      flower shop, because sufficient avoidance of airborne inhalant exposure was not
      considered practical.

PMID- 11526528
TI  - Advances in bioartificial liver devices.

PMID- 11526529
TI  - Water movement across rat bile duct units is transcellular and channel-mediated.
AB  - In recent studies using freshly isolated rat cholangiocytes, we established that
      water crosses the cholangiocyte membrane by a channel-mediated mechanism
      involving aquaporins, a family of water-channel proteins. Our goal was to address
      the importance of channel-mediated water transport in ductal bile formation by
      employing a physiologic experimental model, the enclosed, polarized rat
      intrahepatic bile duct unit (IBDU). Expansion and reduction of luminal areas as a
      reflection of water movement into and out of IBDUs prepared from livers of normal
      rats were measured by quantitative computer-assisted image analysis. When
      enclosed IBDUs were exposed to inward or outward osmotic gradients, their luminal
      area rapidly increased (approximately 25%) or decreased (approximately 20%)
      reflecting net water secretion or absorption, respectively. These effects were
      specifically inhibited by 2 water channel blockers, DMSO and HgCl2. In both
      instances, beta-mercaptoethanol reversed the inhibitory effects. In the absence
      of an osmotic gradient, choleretic agents (secretin and forskolin) and a
      cholestatic hormone (somatostatin) induced a significant increase or decrease of
      IBDU luminal area by 21% and 22%, respectively. These effects were also inhibited
      by DMSO and reversed by beta-mercaptoethanol. Under our experimental conditions,
      DMSO did not interfere with either forskolin-induced cAMP synthesis or the
      generation of osmotic driving forces via the apical chloride-bicarbonate
      exchanger. Protamine, an inhibitor of the paracellular pathway, had no effect on
      hypotonic or forskolin-induced water secretion in IBDUs. These results in a
      physiologically relevant model of ductal bile formation provide additional
      support for the concept that osmotically driven and agonist-stimulated water
      movement into (secretion) and out of (absorption) the biliary ductal lumen is
      transcellular and water channel-mediated.

PMID- 11526530
TI  - Graft dysfunction mimicking autoimmune hepatitis following liver transplantation
      in adults.
AB  - In children, a type of graft dysfunction associated with autoimmune features has
      been described. We have identified 7 adult liver-transplant (LT) recipients from
      a series of over 1,000 consecutive transplant recipients who presented between
      0.3 years and 7.2 years following transplantation with characteristic symptoms,
      autoantibody profiles, and histologic findings of autoimmune disease. The
      indications for transplantation were Ecstasy overdose, alcohol-related cirrhosis,
      primary sclerosing cholangitis (PSC) (2), primary biliary cirrhosis (PBC),
      hepatitis C cirrhosis, and cryptogenic cirrhosis. Two patterns of de novo
      autoantibody development were noted; anti-liver-kidney-microsome (LKM) antibody
      development at high titer in association with an aspartate transaminase (AST) >
      500 and antinuclear (ANA) and antismooth muscle (AMA) antibody development at
      titers >1/80 with lower AST levels. All cases had elevated IgG. Liver biopsies
      showed changes of an autoimmune-type hepatitis with portal and periportal
      hepatitis in association with a marked infiltrate of plasma cells, lymphocytes,
      and bridging collapse. Two patients lost their grafts because of the disease.
      Patients were treated with reintroduction of steroids and azathioprine in cases
      in which it had been withdrawn. Major histocompatibility class I and II
      mismatching did not incur risk. Eight of 12 liver allografts were acquired from
      either DRB*0301- or DRB*0401-positive donors, and 4 recipients were DRB*0301
      positive. This series illustrates that both symptoms and histologic findings of
      graft dysfunction compatible with autoimmune hepatitis (AIH) exist in adult LT
      recipients. Graft loss may be a consequence. This entity may represent a specific
      type of rejection that should currently be classified as "graft dysfunction
      mimicking autoimmune hepatitis."

PMID- 11526531
TI  - Effects of a long-acting formulation of octreotide on renal function and renal
      sodium handling in cirrhotic patients with portal hypertension: a randomized,
      double-blind, controlled trial.
AB  - Octreotide seems to have a beneficial effect on variceal bleeding, and long-term
      administration for the prevention of rebleeding is currently being evaluated.
      Experimental studies have suggested a beneficial effect of chronic octreotide
      treatment on renal function, while clinical studies have shown variable effects.
      Twenty-five cirrhotic patients with portal hypertension were randomized in a
      double-blind design to placebo or a single subcutaneous dose of a long-acting
      formulation of octreotide (octreotide-LAR) (20 mg). Renal function tests were
      performed before dosing and repeated after 30 days. The patients were in sodium
      steady state at the time of study. Glomerular filtration rate (GFR) and effective
      renal plasma flow (ERPF) were measured by a constant infusion clearance
      technique. Renal sodium handling was determined by lithium and sodium clearance
      measurements. Therapeutic serum levels of octreotide along with a reduction of
      insulin-like growth factor I (IGF-I) (P <.01) and an increase of IGF binding
      protein 1 (P <.05) were demonstrated. No effect of octreotide was observed on
      GFR, ERPF, or filtration fraction (GFR/ERPF). Changes in clearance and extraction
      fraction of sodium and lithium during octreotide treatment were not significantly
      different from those of placebo. In addition, no changes in free water clearance,
      urinary flow rate, or 24-hour Na excretion were demonstrated. A significant
      increase of mean arterial pressure (+5 mm Hg; P <.01) was observed after
      treatment with octreotide-LAR. It is concluded that in spite of increased
      arterial pressure, octreotide-LAR has no significant effect on renal hemodynamics
      and tubular function in clinically stable cirrhotic patients with portal
      hypertension.

PMID- 11526532
TI  - A comparative study of antibody expressions in primary biliary cirrhosis and
      autoimmune cholangitis using phage display.
AB  - Primary biliary cirrhosis (PBC) and autoimmune cholangitis (AIC) are serologic
      expressions of an autoimmune liver disease affecting biliary ductular cells.
      Previously we screened a phage-displayed random peptide library with polyclonal
      IgG from 2 Australian patients with PBC and derived peptides that identified a
      single conformational (discontinuous) epitope in the inner lipoyl domain of the
      E2 subunit of the pyruvate dehydrogenase complex (PDC-E2), the characteristic
      autoantigen in PBC. Here we have used phage display to investigate the reactivity
      of PBC sera from 2 ethnically and geographically distinct populations, Japanese
      and Australian, and the 2 serologic expressions, PBC and AIC. Random 7-mer and 12
      mer peptide libraries were biopanned with IgG from 3 Japanese patients with PBC
      and 3 with AIC who did not have anti-PDC-E2. The phage clones (phagotopes)
      obtained were tested by capture enzyme-linked immunosorbent assay (ELISA) for
      reactivity with affinity-purified anti-PDC-E2, and compared with those obtained
      from Australian patients with PBC. Peptide sequences of the derived phagotopes
      and sequences derived by biopanning with irrelevant antisera were aligned to
      develop a guide tree based on physicochemical similarity. Both Australian and
      Japanese PBC-derived phagotopes were distributed in branches of the guide tree
      that contained the peptide sequences MH and FV previously identified as part of
      an immunodominant conformational epitope of PDC-E2, indicating that epitope
      selection was not influenced by the racial origin of the PBC sera. Biopanning
      with either PBC or AIC-derived IgG yielded phagotopes that reacted with anti-PDC
      E2 by capture ELISA, further establishing that there is a similar autoimmune
      targeting in PBC and AIC.

PMID- 11526533
TI  - Increased production of vascular endothelial growth factor in peritoneal
      macrophages of cirrhotic patients with spontaneous bacterial peritonitis.
AB  - Spontaneous bacterial peritonitis (SBP) is a common complication of cirrhotic
      patients with ascites that usually results in renal failure and death despite the
      efficacy of the current antibiotic therapy. The pathogenesis of these phenomena
      is poorly known but it has been related to the production of vasoactive cell
      mediators locally acting on the splanchnic vasculature. Because previous studies
      showed that peritoneal macrophages of cirrhotic patients may produce high
      quantities of vascular endothelial growth factor (VEGF), a powerful vessel
      permeabilizing agent, when stimulated by cytokines and bacterial
      lipopolysaccharide, the present study was aimed to seek whether peritoneal
      macrophages of SBP patients are induced to produce increased amounts of VEGF. Our
      results indicate that the production rate and the messenger RNA (mRNA) and
      protein expression of this substance are increased in macrophages of patients
      with SBP in comparison with those of noninfected cirrhotic patients. This
      characteristic feature is absent in circulating monocytes of these patients.
      Moreover, enhanced endothelial cell proliferation induced by conditioned medium
      of macrophages isolated from the ascites of patients with SBP is abolished by
      anti-VEGF antibody, and peritoneal tissue of cirrhotic patients expresses both
      VEGF receptors, Flt-1 and KDR. These results, therefore, are consistent with the
      concept that locally released macrophage-derived VEGF may result in increased
      vascular permeability and plasma leakage in the peritoneal vessels of cirrhotic
      patients with SBP.

PMID- 11526534
TI  - Distinct epitopes on formiminotransferase cyclodeaminase induce autoimmune liver
      cytosol antibody type 1.
AB  - Liver cytosol antibody type 1 (LC1) is regarded as a serologic marker of type 2
      autoimmune hepatitis, in addition to liver kidney microsomal antibody type 1.
      Among 38 patients with type 2 autoimmune hepatitis, 23 were positive for LC1
      antibodies. The antigen recognized by LC1 has been identified as a liver-specific
      58-kd metabolic enzyme named formiminotransferase cyclodeaminase (FTCD). All 23
      LC1-positive sera immunoprecipitated rat FTCD, and 22 gave an identity reaction
      with rat FTCD by immunodiffusion. No reaction was observed with sera from 10
      patients with type 1 autoimmune hepatitis, 10 with primary biliary cirrhosis, 10
      with chronic hepatitis C, and 10 healthy controls. By Western immunoblotting all
      23 LC1-positive sera and all the controls tested negative, suggesting that all
      the antigenic epitopes were destroyed by denaturation. FTCD is a bifunctional
      protein composed of distinct globular FT and CD domains connected by a short
      linker. To identify epitopes that trigger the LC1 autoimmune response, we tested
      LC1 antibodies against FTCD constructs encoding the N-terminal FT domain (amino
      acids 1-339), or the C-terminal CD domain (amino acids 332-541). Of 20 sera
      positive against full-length FTCD, 8 (40%) recognized the FT domain and the CD
      domain, 7 (35%) recognized only the FT domain, and 5 (25%) did not recognize
      either construct. No sera reacted with only the CD domain. These data indicate
      that multiple regions of FTCD trigger the LC1 autoimmune response, and that LC1
      reactivity is mainly directed to conformation-sensitive epitopes located in the
      FT region of FTCD.

PMID- 11526535
TI  - Hepatocellular carcinomas in native livers from patients treated with orthotopic
      liver transplantation: biologic and therapeutic implications.
AB  - The gross and histopathologic characteristics of 212 nonfibrolamellar
      hepatocellular carcinomas (HCCs) discovered in native livers removed at the time
      of liver transplantation were correlated with features of invasive growth and
      tumor-free survival. The results show that most HCCs begin as small well
      differentiated tumors that have an increased proliferation rate and induce
      neovascularization, compared with the surrounding liver. But at this stage, they
      maintain a near-normal apoptosis/mitosis ratio and uncommonly show vascular
      invasion. As tumors enlarge, foci of dedifferentiation appear within the
      neoplastic nodules, which have a higher proliferation rate and show more
      pleomorphism than surrounding better-differentiated areas. Vascular invasion,
      which is the strongest predictor of disease recurrence, correlates significantly
      with tumor number and size, tumor giant cells and necrosis, the predominant and
      worst degree of differentiation, and the apoptosis/mitosis ratio. In the absence
      of macroscopic or large vessel invasion, largest tumor size (P <.006),
      apoptosis/mitosis ratio (P <.03), and number of tumors (P <.04) were independent
      predictors of tumor-free survival and none of 24 patients with tumors having an
      apoptosis/mitosis ratio greater than 7.2 had recurrence. A minority of HCCs
      (<15%) quickly develop aggressive features (moderate or poor differentiation, low
      apoptosis/mitosis ratio, and vascular invasion) while still small, similar to
      flat carcinomas of the bladder and colon. In conclusion, hepatic carcinogenesis
      in humans is a multistep and multifocal process. As in experimental animal
      studies, aggressive biologic behavior (vascular invasion and recurrence)
      correlates significantly with profound alterations in the apoptosis/mitosis ratio
      and with architectural and cytologic alterations that suggest a progressive
      accumulation of multiple genetic abnormalities.

PMID- 11526536
TI  - Mechanisms of cell death induced by suicide genes encoding purine nucleoside
      phosphorylase and thymidine kinase in human hepatocellular carcinoma cells in
      vitro.
AB  - For gene therapy of hepatocellular carcinoma (HCC), the Escherichia coli purine
      nucleoside phosphorylase (PNP)/fludarabine suicide gene system may be more useful
      than the herpes simplex virus thymidine kinase/ganciclovir (HSV-tk/GCV) system as
      a result of a stronger bystander effect. To analyze the molecular mechanisms
      involved in PNP/fludarabine-mediated cell death in human HCC cells in comparison
      with HSV-tk/GCV, we transduced human HCC cells of the cell lines, HepG2 and
      Hep3B, with PNP or HSV-tk using adenoviral vectors, followed by prodrug
      incubation. Both systems predominantly induced apoptosis in HepG2 and Hep3B
      cells. PNP/fludarabine induced strong p53 accumulation and a more rapid onset of
      apoptosis in p53-positive HepG2 cells as compared with p53-negative Hep3B cells,
      but efficiency of tumor cell killing was similar in both cell lines. In contrast,
      HSV-tk/GCV-induced apoptosis was reduced in p53-negative Hep3B cells as compared
      with p53-positive HepG2 cells. HSV-tk/GCV, but not PNP/fludarabine, caused up
      regulation of Fas in p53-positive HepG2 cells and of Fas ligand (FasL) in both
      HCC cell lines. These results demonstrate cell line-specific differences in
      response to treatment with PNP/fludarabine and HSV-tk/GCV, respectively, and
      indicate that PNP/fludarabine may be superior to HSV-tk/GCV for the treatment of
      human HCC because of its independence from p53 and the Fas/FasL system.

PMID- 11526537
TI  - A modified choline-deficient, ethionine-supplemented diet protocol effectively
      induces oval cells in mouse liver.
AB  - Several reliable and reproducible methods are available to induce oval cells in
      rat liver. Effective methods often involve inhibiting proliferation in
      hepatocytes using an alkylating agent, then subjecting the rat to partial
      hepatectomy (PH). The surgery is difficult to perform reproducibly in mice.
      Approaches that do not include partial hepatectomy, such as administration of D
      galactosamine, are ineffective in mice. We found that a choline-deficient,
      ethionine-supplemented (CDE) diet, which is very effective in rats, leads to high
      morbidity and mortality when administered to mice. This article outlines an
      alternative protocol by which a CDE diet can be administered to mice. This diet
      is shown to be highly effective for oval cell induction, without causing high
      mortality. It takes less time and is at least as effective as other commonly used
      protocols for inducing oval cells in mice.

PMID- 11526538
TI  - High rates of hepatocellular carcinoma in cirrhotic patients with high liver cell
      proliferative activity.
AB  - The prevalence, risk factors, and clinical significance of high liver cell
      proliferative activity were investigated in 208 well-compensated cirrhotic
      patients (150 men; 50 years; 135 with chronic hepatitis C) who had been under
      prospective surveillance for hepatocellular carcinoma (HCC) with annual abdominal
      ultrasound (US) and serum alpha-fetoprotein (AFP) determination. Immunostaining
      for proliferating cell nuclear antigen (PCNA) was employed to assess liver cell
      proliferative activity in formalin-fixed, paraffin-embedded liver specimens. The
      percentage of reactive nuclei was calculated by a computer-assisted image
      analysis system. The overall PCNA labeling index (LI) ranged from 0.1% to 12.5%
      (mean, 2.1%), being significantly higher in the 50 patients who developed HCC
      during 88 +/- 42 months of follow-up than in the 158 patients who remained cancer
      free (3.6% +/- 2.4% vs. 1.6% +/- 1.5%; P <.0001). By receiver operating curve
      (ROC), a 2.0% cut-off value of PCNA-LI discriminated between patients at high and
      low risk for developing cancer. By multivariate analysis, high histologic grading
      scores and gender were associated to PCNA LI >2.0%. The yearly incidence of HCC
      was 5.2% for the 80 patients with PCNA-LI >2.0% compared with 1.1% for the 128
      with low PCNA-LI (relative risk, 4.90; 95% CI, 2.63-9.55). By multivariate
      analysis, PCNA-LI >2.0% was the strongest independent predictor of cancer (hazard
      ratio, 5.49; 95% CI, 2.90-10.37). Overall, survival was significantly lower in
      patients with high liver cell proliferative activity rates than in those with low
      proliferative rates (10% vs. 75%; P <.0001). In conclusion, development of HCC in
      patients with compensated cirrhosis seems to be reliably predicted by liver cell
      proliferation status.

PMID- 11526539
TI  - Discrimination value of the new western prognostic system (CLIP score) for
      hepatocellular carcinoma in 662 Japanese patients. Cancer of the Liver Italian
      Program.
AB  - To reliably estimate the prognoses of patients with hepatocellular carcinoma
      (HCC), both liver function and tumor-related factors should be accounted for.
      However, there are few worldwide staging systems that assess prognostic value in
      the context of selecting individual patients for randomized stratification in
      therapeutic and clinical trials. We investigated the value of known prognostic
      systems and verified the usefulness of the new scoring system proposed by the
      Cancer of the Liver Italian Program (CLIP), as determined from 662 Japanese
      patients. A retrospective analysis of the HCC diagnoses at 4 Japanese
      institutions from 1990 and 1998 was performed. Overall survival was the only end
      point used in the analysis. Discriminatory ability and predictive power of the
      CLIP score were compared with those of Okuda stage and AJCC TNM stage. Compared
      with the Okuda and AJCC staging systems, the CLIP score's enhanced discriminatory
      capacity, which was tested by the linear trend test and Harrels' c-index,
      revealed a class of patients with an impressively more favorable prognosis and
      another class with a relatively shorter life expectancy. Moreover, the likelihood
      ratio test showed that the CLIP score had additional homogeneity of survival
      within each score above that of the Okuda stage or the AJCC stage. This was true
      for 3 subgroups of patients who received surgery, transcatheter arterial
      chemoembolizations, and percutaneous ethanol injections. Collectively, these
      findings indicate that the CLIP score has the highest stratification ability with
      regard to prognosis in patients with HCC. The CLIP score could be used
      internationally to stratify randomization groups in therapeutic and clinical
      trials.

PMID- 11526540
TI  - Low-molecular-weight hyaluronic acid induces nuclear factor-kappaB-dependent
      resistance against tumor necrosis factor alpha-mediated liver injury in mice.
AB  - Liver resident NK1.1+ T cells are supposed to play a pivotal role in the onset of
      inflammatory liver injury in experimental mouse models such as concanavalin A
      (Con A)-induced hepatitis. These cells, expressing the adhesion receptor, CD44,
      are largely depleted from the liver by a single intravenous injection of low
      molecular-weight fragments of hyaluronic acid (LMW-HA). Here, we report that LMW
      HA pretreatment protected mice from liver injury in several models of T-cell- and
      macrophage-dependent, tumor necrosis factor alpha (TNF-alpha)-mediated
      inflammatory liver injury, i.e., from liver injury induced by either Con A or
      Pseudomonas exotoxin A (PEA) or PEA/lipopolysaccharide (LPS). Interestingly,
      apart from inhibition of cellular adhesion, pretreatment of mice with LMW-HA was
      also capable of preventing hepatocellular apoptosis and activation of caspase-3
      induced by direct administration of recombinant murine (rmu) TNF-alpha to D
      galactosamine (GalN)-sensitized mice. LMW-HA-induced hepatoprotection could be
      neutralized by pretreatment with the nuclear factor-kappaB (NF-kappaB) inhibitor,
      pyrrolidine dithiocarbamate (PDTC), demonstrating the involvement of NF-kappaB in
      the observed protective mechanism. Indeed, injection of LMW-HA rapidly induced
      the production of TNF-alpha by Kupffer cells and the translocation of NF-kappaB
      into hepatocellular nuclei. Both LMW-HA-induced TNF-alpha production and NF
      kappaB translocation were blocked by pretreatment with PDTC. Our findings provide
      evidence for an unknown mechanism of LMW-HA-dependent protection from
      inflammatory liver disease, i.e., induction of TNF-alpha- and NF-kappaB-dependent
      cytoprotective proteins within the target parenchymal liver cells.

PMID- 11526541
TI  - Activation of caspases occurs downstream from radical oxygen species production,
      Bcl-xL down-regulation, and early cytochrome C release in apoptosis induced by
      transforming growth factor beta in rat fetal hepatocytes.
AB  - Most of the morphologic changes that are observed in apoptotic cells are caused
      by a set of cysteine proteases (caspases) that are activated during this process.
      In previous works from our group we found that treatment of rat fetal hepatocytes
      with transforming growth factor beta1 (TGF-beta1) is followed by apoptotic cell
      death. TGF-beta1 mediates radical oxygen species (ROS) production that precedes
      bcl-xL down-regulation, loss of mitochondrial transmembrane potential, release of
      cytochrome c, and activation of caspase-3 (Herrera et al., FASEB J 2001;15:741
      751). In this work, we have analyzed how TGF-beta1 activates the caspase cascade
      and whether or not caspase activation precedes the oxidative stress induced by
      this factor. Our results show that TGF-beta1 activates at least caspase-3, -8,
      and -9 in rat fetal hepatocytes, which are not required for ROS production,
      glutathione depletion, bcl-xL down-regulation, and initial cytochrome c release.
      However, caspase activation mediates cleavage of Bid and Bcl-xL that could
      originate an amplification loop on the mitochondrial events. An interesting
      result is that transmembrane potential disruption occurs later than the initial
      cytochrome c release and is mostly blocked by the pan-caspase inhibitor Z
      VAD.fmk, indicating that the decrease in mitochondrial transmembrane potential
      (Delta(Psi)m) may be a consequence of caspase activity rather than the mechanism
      by which TGF-beta induces cytochrome c efflux. Finally, although Z-VAD.fmk
      completely blocks nucleosomal DNA fragmentation, it only delays cell death, which
      suggests that activation of the apoptotic program by TGF-beta in fetal
      hepatocytes inevitably leads to death, with or without caspases.

PMID- 11526542
TI  - Human liver regeneration: hepatic energy economy is less efficient when the organ
      is diseased.
AB  - Recovery of liver cell mass following hepatectomy requires a metabolic compromise
      between differentiated function and organ regrowth. Clinical experience has shown
      that hepatic failure after resection is more common when the organ is diseased.
      We have evaluated intracellular hepatic biochemistry in patients with normal and
      cirrhotic livers undergoing partial hepatectomy, using 31-phosphorus magnetic
      resonance spectroscopy ((31)P MRS). Eighteen patients were studied, half with
      normal liver architecture (normal group, n = 9) and half with cirrhotic
      parenchyma (cirrhosis group, n = 9). Magnetic resonance examinations were
      performed preoperatively and on postoperative days 2, 4, 6, 14, and 28. Hepatic
      volume (estimated by magnetic resonance imaging [MRI]) and blood chemistries were
      measured at the same intervals. Following a comparable reduction in parenchymal
      volume, the cirrhotic group demonstrated a more sustained fall in adenosine
      triphosphate (ATP) energy state. Disturbance of membrane phospholipid metabolism
      and duration of acute-phase reaction were more marked when the liver was
      diseased. The pattern of derangement of hepatic function, however, was similar in
      the two groups. Overall, the recovery process was less efficient in the cirrhotic
      organ, and culminated in a diminished rate and extent of the regenerative
      response. These outcomes indicate that liver regeneration after partial
      hepatectomy involves modulation of hepatic energy economy in response to changing
      work demands. The efficiency of this process is influenced by the histopathologic
      state of the organ, and in turn governs the physiologic reserve. These findings
      may explain the mechanism of posthepatectomy liver failure, and offer a rational
      basis for the assessment of novel hepatic support strategies.

PMID- 11526543
TI  - Acquisition of susceptibility to hepatitis C virus replication in HepG2 cells by
      fusion with primary human hepatocytes: establishment of a quantitative assay for
      hepatitis C virus infectivity in a cell culture system.
AB  - Hepatitis C virus (HCV) replicates in human and chimpanzee hepatocytes. To
      characterize the nature of HCV and evaluate antiviral agents, the development of
      an HCV replication system in a cell culture is essential. We developed a cell
      line derived from human hepatocytes by fusing them with a hepatoblastoma cell
      line, HepG2, and obtained several clones. When we tested the clones for their
      ability to support HCV replication by nested RT-PCR, we found 1 clone (IMY-N9)
      that was more susceptible to HCV replication than HepG2. The negative-strand HCV
      RNA was detected in IMY-N9 by strand-specific RT-PCR, and viral RNA was
      identified in culture supernatant during the culture. Then we monitored HCV RNA
      titers in IMY-N9 and HepG2, respectively, by real-time detection PCR throughout
      the culture. A significant increase in the HCV RNA titer was observed only in IMY
      N9. Serial passages of HCV culture supernatant were shown in the culture system.
      Furthermore, we tested several infectious materials for viral infectivity by
      monitoring HCV RNA titers and/or 50% tissue culture infectious dose (TCID50) of
      HCV on IMY-N9. In each material, HCV showed various growth patterns and a
      different TCID50 even though the PCR titer in each material was identical. The
      results showed that HCV in each material served various growth patterns and
      different TCID50 even though PCR titer in each material was identical. This cell
      line is useful for estimating viral activity and for studying cellular factors
      that may be necessary to HCV replication in human hepatocytes.

PMID- 11526544
TI  - Sequential treatment with lamivudine and interferon monotherapies in patients
      with chronic hepatitis B not responding to interferon alone: results of a pilot
      study.
AB  - Sustained viral suppression using monotherapy with interferon alfa (IFN-alpha) or
      lamivudine can only be achieved in a small percentage of patients with chronic
      hepatitis B. The concomitant administration of lamivudine and IFN-alpha does not
      enhance efficacy. We postulated that the optimal timing of therapy might be
      sequential treatment with lamivudine and IFN-alpha. The aim of this study was
      therefore to assess the efficacy of sequential treatment in patients resistant to
      IFN-alpha alone. Fourteen male patients, with a median age of 40 years,
      nonresponders to IFN-alpha with hepatitis B virus (HBV) DNA > 100 pg/mL (branched
      DNA [bDNA] Chiron) and positive hepatitis B e antigen (HBeAg) in 11 of 14
      patients, were treated with lamivudine 100 mg/d alone for 20 weeks, then with
      both IFN-alpha2b 5 MU 3 times per week and lamivudine for 4 weeks, and lastly
      with IFN-alpha alone for 24 weeks. At the end of lamivudine therapy, all patients
      had undetectable serum HBV DNA, and none exhibited an emergence of HBV polymerase
      mutant or breakthrough. Sustained serum HBV-DNA clearance 6 months after the end
      of sequential treatment was achieved in 8 of 14 patients, HBeAg-to-anti-HBe
      seroconversion in 5 of 11 patients, and HBeAg and hepatitis B surface antigen
      (HBsAg) seroconversions in 3 of 14 patients (anti-HBs > 100 IU/mL). All sustained
      responders had normalized their alanine transaminase (ALT) values and exhibited
      histologic improvements. In conclusion, the results of this pilot study suggest
      that sequential treatment with lamivudine and IFN-alpha can induce a sustained
      virologic response, including HBs seroconversion, in patients with chronic
      hepatitis B not responding to IFN-alpha alone, without the selection of drug
      resistant mutants. This therapeutic schedule warrants further evaluation in
      clinical trials.

PMID- 11526545
TI  - Safety and efficacy of oral entecavir given for 28 days in patients with chronic
      hepatitis B virus infection.
AB  - Entecavir is an oral antiviral drug with selective activity against hepatitis B
      virus (HBV). We conducted a randomized, placebo-controlled, dose-escalating study
      in patients with chronic hepatitis B infection in which we evaluated the efficacy
      and safety of entecavir given for 28 days. Follow-up was 24 weeks. All doses of
      entecavir (0.05 mg, 0.1 mg, 0.5 mg, and 1.0 mg) showed a pronounced suppression
      of replication of the HBV with a 2.21, 2.29, 2.81, and 2.55 mean log(10)
      reduction of viral load, respectively. Approximately 25% of patients on entecavir
      showed a decline of HBV DNA below the limit of detection of the Chiron HBV-DNA
      assay (<0.7 MEq/mL). In the postdosing follow-up period patients who were treated
      with 0.5 and 1.0 mg of entecavir showed a considerably slower return in their HBV
      DNA levels to baseline compared with those patients treated with lower dosages (P
      <.05). All doses of entecavir were well tolerated with no significant difference
      between treated patients and those receiving placebo. No significant changes in
      alanine transaminase (ALT) levels within the dose groups and the placebo group
      between baseline and the end of treatment were observed. Three patients (9%) (1
      each in the 0.05-, 0.1-, and 0.5-mg groups) experienced asymptomatic hepatitis
      flares 16 weeks (2 patients) and 24 weeks (1 patient) after withdrawal of
      entecavir. In conclusion, in this 28-day study of entecavir a pronounced decrease
      of HBV DNA was observed and there were no significant side effects in entecavir
      patients in comparison with placebo-treated patients.

PMID- 11526546
TI  - Hepatitis B virus variants in patients receiving lamivudine treatment with
      breakthrough hepatitis evaluated by serial viral loads and full-length viral
      sequences.
AB  - Both viral loads and genome variations have been implicated in the pathogenesis
      of acute exacerbation of chronic hepatitis B. Hepatitis B exacerbation in
      patients receiving lamivudine treatment represented a unique setting to clarify
      their importance. Three organ recipients with posttransplantation hepatitis B
      exacerbation and 3 patients with chronic hepatitis B were studied. All received
      lamivudine treatment and their alanine aminotransferase (ALT) levels and
      hepatitis B virus (HBV) loads were regularly followed. Full-length genomic
      sequences before and during lamivudine treatment were determined in patients who
      had breakthrough of serum HBV DNA or elevation of serum ALT. Breakthrough of
      serum HBV DNA occurred after 6 to 15 months of lamivudine treatment in all. A
      rapid increase of viral load accompanying the emergence of tyrosine-methionine
      aspartate-aspartate (YMDD) variant was followed by hepatitis B exacerbation in
      each patient. The mean number of nucleotide and amino acid substitutions per
      genome pair was equivalent in immunosuppressed or immunocompetent patients (6.3
      vs. 6.3 for nucleotide, P >.05; 6.0 vs. 6.7 for amino acid, P >.05). Changes of
      nucleotide and amino acid beyond the YMDD motif were distributed along the whole
      HBV genome but none occurred within the known B-cell epitopes and human leukocyte
      antigen class I- or II-restricted T-cell epitopes. Our results suggest that a
      resurgence of viral load rather than changes of the known immunogenic viral
      epitopes is more closely associated with the development of hepatitis B
      exacerbation after the emergence of YMDD variants in patients receiving
      lamivudine treatment.

PMID- 11526547
TI  - Geographic distribution of hepatitis B virus (HBV) genotype in patients with
      chronic HBV infection in Japan.
AB  - The geographic distribution of hepatitis B virus (HBV) genotypes in Japan and its
      clinical relevance are poorly understood. We studied 731 Japanese patients with
      chronic HBV infection. HBV genotype was determined by the restriction fragment
      length polymorphism (RFLP) method after polymerase chain reaction (PCR). Of the
      720 patients with positive PCR, 12 (1.7%) were HBV genotype A, 88 (12.2%) were
      genotype B, 610 (84.7%) were genotype C, 3 (0.4%) were genotype D, and 7 (1.0%)
      were of mixed genotype. Over 94% of patients on the Japanese mainland had
      genotype C, while 60% of the patients on Okinawa, the most southern islands, and
      22.9% in the Tohoku area, the northern part of the mainland, harbored genotype B.
      Compared with genotype C patients, genotype B patients were older (53.6 to 42.2
      years; P <.01), had a lower rate of positive hepatitis B e antigen (HBeAg) (18.4%
      to 50.6%; P <.01), and a lower level of serum HBV DNA (5.02 to 5.87 log genome
      equivalents (LGE)/mL; P <.01). The mean age of the genotype B patients with
      hepatocellular carcinoma was 70.1 +/- 9.2 years, compared with 55.2 +/- 9.7 of
      genotype C patients (P <.01). These results indicate that genotypes C and B are
      predominant in Japan, and there are significant differences in geographic
      distribution and clinical characteristics among the patients with the different
      genotypes.

PMID- 11526548
TI  - Complementary and alternative medicine in chronic liver disease.

PMID- 11526549
TI  - Liver transplantation in the elderly: is caution warranted?

PMID- 11526550
TI  - Cytochrome c: which way out?

PMID- 11526551
TI  - Tumor dissemination after radiofrequency ablation of hepatocellular carcinoma.

PMID- 11526552
TI  - Tumor dissemination after radiofrequency ablation of hepatocellular carcinoma.

PMID- 11526553
TI  - Tumor dissemination after radiofrequency ablation of hepatocellular carcinoma.

PMID- 11526554
TI  - Tumor dissemination after radiofrequency ablation of hepatocellular carcinoma.

PMID- 11526555
TI  - Maintaining professionalism in a managed care environment.

PMID- 11526556
TI  - A comparison of discectomy and arthroscopic lysis and lavage for the treatment of
      chronic closed lock of the temporomandibular joint: a randomized outcome study.
AB  - PURPOSE: The study compared the efficacy of discectomy or arthroscopic lysis and
      lavage in patients with chronic closed lock of the temporomandibular joint (TMJ)
      in a prospective, randomized clinical trial. PATIENTS AND METHODS: Twenty-two
      patients with a clinical diagnosis of chronic closed lock were prospectively
      randomized to either discectomy or arthroscopic lysis and lavage. The individual
      outcome in each patient was evaluated with a visual analog scale for pain and a
      questionnaire concerning mandibular functional impairment. The clinical
      evaluation included measurement of maximum interincisal opening and protrusion,
      recording of clicking and crepitation, and palpation for tenderness of the TMJ
      and jaw muscles. Recordings were made before the operation (baseline) and at the
      1-year follow-up. RESULTS: Twenty patients completed the study. Discectomy and
      arthroscopic lysis and lavage significantly reduced pain and improved mandibular
      function. Discectomy reduced pain somewhat more effectively than arthroscopic
      lysis and lavage. The clinical recordings at the 1-year follow-up indicated
      similarly good outcomes after both procedures. CONCLUSION: Both discectomy and
      arthroscopic lysis and lavage are effective surgical methods for treatment of
      chronic closed lock of the TMJ. Considering that arthroscopic lysis and lavage is
      a minimally invasive outpatient procedure, it should be used as the first choice
      in surgical treatment of this condition.

PMID- 11526558
TI  - The use of intra-articular opioids and bupivacaine for analgesia following
      temporomandibular joint arthroscopy: a prospective, randomized trial.
AB  - PURPOSE: This investigation evaluated the efficacy of using intra-articular
      morphine, bupivacaine, or a combination of both in the management of
      postarthroscopy temporomandibular joint (TMJ) pain. MATERIALS AND METHODS: Thirty
      two consecutive patients with internal derangements of the TMJ and persistent
      pain underwent TMJ arthroscopy. The patients were randomized equally into 4
      groups. Group 1 received a sterile saline solution (control), group 2 received
      bupivacaine alone, group 3 received only a morphine solution, and group 4
      received morphine mixed with bupivacaine. The patients recorded postarthroscopy
      pain using a visual analog scale (VAS), as well as analgesic consumption for 24
      hours. The VAS and analgesic consumption were compared in the 4 groups. RESULTS:
      Group 3 (bupivacaine alone) consumed, on average, 5.1 fewer analgesic equivalents
      than did group 1 (control) over the 24-hour period of study (P <.05). Otherwise,
      there was no significant difference in the number of analgesic equivalents
      consumed by the 4 groups. Patients treated with bupivacaine alone and those with
      morphine alone had significantly lower pain scores than the controls. However,
      there was no significant difference between the pain scores of the morphine and
      bupivacaine groups at any time. Patients treated with the mixture of morphine and
      bupivacaine showed no significant difference from controls at any time.
      CONCLUSIONS: Bupivacaine alone provides a better analgesic effect than morphine
      alone or the combination of morphine and bupivacaine. Morphine alone has a longer
      time of onset, with less effect on the pain scores during the 24-hour observation
      period.

PMID- 11526560
TI  - The use of autogenous vein grafts for inferior alveolar and lingual nerve
      reconstruction.
AB  - PURPOSE: This study evaluated whether an autogenous vein graft forms a
      satisfactory conduit for nerve regeneration. PATIENTS AND METHODS: Fifteen
      patients received a total of 16 autogenous vein grafts to repair continuity
      defects of the inferior alveolar (6) and lingual nerves (10) nerves. All were
      treated between 4 and 10 months after injury. At surgery, the postresection
      defects ranged from 2 to 14 mm. All lingual nerves were repaired with saphenous
      vein grafts from an intraoral approach and all inferior alveolar nerves were
      repaired with facial vein grafts inserted from an extraoral approach. RESULTS:
      Lingual nerve repair in 3 cases where the gap between the nerve ends was 5 mm or
      less resulted in some return of sensation. In 7 cases where the gap was between 5
      and 14 mm, there was no return of sensation. In the 6 inferior alveolar nerve
      repairs there was some return of sensation in all cases and there was good return
      of sensation in 3 cases. One patient redeveloped dysesthesia in the inferior
      alveolar nerve and subsequently had a neurectomy. Histologic material was
      available from this case. CONCLUSIONS: It appears that a vein graft can form a
      physiologic conduit for nerve regeneration. The results are more successful with
      shorter gaps, which indicates that, in some respects, the vein acts like a
      barrier membrane. The increased success rate in the inferior alveolar nerve
      repair may be because the vein remains straight and patent in the inferior
      alveolar canal. The lack of success with a long lingual nerve gap repair may be
      because the vein is collapsed or kinked by movement of the tongue, which may
      inhibit neural regeneration. Therefore, vein grafts should not be used for long
      lingual nerve continuity defects.

PMID- 11526562
TI  - Immediate postexpansion changes following the use of the transpalatal distractor.
AB  - PURPOSE: This study analyzed the immediate postexpansion positional changes of
      the maxillary halves resulting from the use of the transpalatal distractor (Surgi
      Tec NV, Bruges, Belgium). PATIENTS AND METHODS: Corticotomies were performed in
      the same way as surgically assisted rapid palatal expansion, all from a buccal
      sulcus approach. Titanium abutment plates with box extension were placed
      horizontally in the vertical wall of the palatal vault overlying the second
      premolar root through a mucoperiosteal incision and fixed with titanium screws 5
      mm in length. An appropriate telescopic distraction module was fitted in the
      slots of the boxes. Expansion started 1 week after surgery, at a rate of 0.33
      mm/d. Digital measurements on digital photographs of the models were obtained
      from 20 postadolescent patients before and immediately after transpalatal
      distraction. The distractor was placed at the level of the second premolar.
      Pterygomaxillary separation was not performed. Changes in the intercanine,
      interpremolar and intermolar width, in the dental arch perimeter, and in the
      premolar and molar angulations in the frontal plane were analyzed and correlated.
      RESULTS: Width expansions of 35.7%, 31.7%, and 22.7% were noted in the canine,
      premolar, and molar regions, respectively. There was a mean increase of the arch
      perimeter of 10.5%, which correlated well (P <.001) with the expansion at the
      canine and premolar level. The mean angulation changes in the frontal plane of
      the premolar and molar segments were minimal, -8.3 degrees +/- 9.6 degrees and
      0.9 degrees +/- 9.9 degrees, respectively. The change in angulation at the molar
      level correlated (P <.005) with the amount of expansion in that region. Premolar
      angulation did not correlate with the expansion, and segment angulation did not
      correlate with age. CONCLUSIONS: The expansion at the canine level was 1.5 times
      greater than at the molar level (corrected value relative to the original
      intermolar width). The change in arch perimeter can be predicted from the
      expansion at the canine and premolar level. Expansion in the frontal plane occurs
      with little tipping of the segments.

PMID- 11526564
TI  - Disc mobility and arthroscopic condition of the temporomandibular joint
      associated with long-term mandibular discontinuity.
AB  - PURPOSE: The present study aimed to explore disc mobility and arthroscopically
      diagnosed morphologic changes in the temporomandibular joint (TMJ) associated
      with long-term mandibular discontinuity. PATIENTS AND METHODS: Twelve patients
      (24 TMJs) who had undergone mandibulectomy including the unilateral condyle or
      segmental mandibulectomy without mandibular reconstruction, more than 8 months
      before this study were examined. The 24 TMJs were classified into 3 groups as
      follows: group 1, TMJs with a major mandibular fragment including the mandibular
      body (n = 11); group 2, TMJs with a mandibular ramus including the coronoid
      process (n = 5); and group 3, TMJs with only a condylar process, a mandibular
      ramus not including the coronoid process, or without a condyle (n = 8). Disc
      mobility was evaluated by magnetic resonance imaging, and arthroscopic
      observation of the superior joint compartment (SJC) was performed in all TMJs.
      The relationship between disc mobility and the arthroscopic findings was also
      studied. RESULTS: The frequency of immobile discs differed significantly among
      groups 1 (0%), 2 (40.0%), and 3 (100%). Arthroscopic findings were normal in all
      SJCs of group 1. Various types of fibrous adhesions were observed in 40.0% of
      group 2 and in 75.0% of group 3. The development of fibrous adhesions in the SJC
      was significantly related to the presence of an immobile disc. CONCLUSIONS: Long
      term immobilization of the TMJ in a nonfunctional state seems to promote the
      development of fibrous adhesions in the SJC. Preservation of the mandibular
      fragment including the coronoid process, during mandibulectomy appears to
      contribute to postoperative TMJ mobility. To ensure recovery of a physiologic TMJ
      after mandibulectomy, it seems important to re-establish TMJ mobility by
      establishing mandibular continuity as soon as possible.

PMID- 11526566
TI  - Management of oral squamous cell carcinoma treated with inadequate excisional
      biopsy.
AB  - PURPOSE: When an initial "excisional biopsy" has been performed on a primary oral
      carcinoma, microscopic tumor may remain and the usual landmarks that enable the
      surgeon to plan his safe margin are destroyed. This article analyzes the impact
      that such a biopsy may have on treatment and patient outcome. PATIENTS AND
      METHODS: A retrospective chart review of a consecutive series of 350 oral cancer
      patients treated by 1 surgeon in an 8-year period identified 33 (9.4%) patients
      who originally had inadequate excisional biopsies. Exclusion criteria eliminated
      7 patients who were lost to follow-up or who had undergone previous treatment
      with radiation therapy or chemotherapy. Data extracted included age, sex, race,
      primary intraoral site, estimated tumor (T) stage, method of treatment,
      histology, follow-up, and outcome. RESULTS: Twenty-four of the 26 patients
      underwent re-excision of their oral cancer. Ten of these patients (38.4%) also
      underwent selective neck dissection. Fifteen of the 24 patients (62.5%) had
      residual carcinoma identified in the re-excision specimen, and 3 of the patients
      who underwent elective neck dissection had micrometastasis identified. The
      patients were followed for an average of 35.5 months. Two of 24 (8.3%) patients
      had local recurrence at 36 and 84 months, respectively. Both patients were
      managed with re-excision and are still alive with no evidence of disease. Of the
      10 patients originally treated with elective neck dissection, there has been no
      regional recurrence. However, of the 14 patients who underwent re-excision of the
      lesion without neck dissection, 3 developed regional disease at 1, 5, and 6
      months, respectively, postoperatively. These patients underwent neck dissection
      and radiation therapy. Two patients are alive with no evidence of disease, and
      the third died of a second primary lung cancer. Twenty-five of the 26 patients
      (96.2%) are still alive and well with no evidence of disease. CONCLUSIONS:
      Patients who have had inadequate excisional biopsies can be effectively managed
      with re-excision plus neck dissection when indicated by T stage or more than 3 mm
      depth of invasion.

PMID- 11526568
TI  - Sensory nerve impairment following mandibular third molar surgery.
AB  - PURPOSE: This prospective study reports the rate and factors influencing sensory
      impairment of the inferior alveolar and lingual nerves after the removal of
      impacted mandibular third molars under local anesthesia. PATIENTS AND METHODS:
      There were 741 patients with 741 mandibular third molars removed under local
      anesthesia during a 3-year period from 1994 to 1997. Standardized data collection
      included the patient's name, age and gender, side of operation, angulation of the
      tooth, lingual flap elevation, use of vertical or horizontal tooth division, the
      experience of the operator, and the occurrence of lingual and/or inferior
      alveolar nerve paresthesia. RESULTS: Postoperative lingual nerve paresthesia
      occurred in 19 patients (2.6%). There was a highly significant increase in the
      incidence associated with raising of a lingual flap (P <.001). The incidence of
      inferior alveolar nerve paresthesia was (3.9%). It was highest in the under 20
      year-old age group (9.8%), and there was a highly significant relationship to the
      experience of the operator (P <.001). Statistical analyses revealed that both
      lingual and inferior alveolar nerve paresthesia were unrelated to the other
      variables. CONCLUSIONS: The elevation of lingual flaps and the experience of the
      operator are significant factors contributing to lingual and inferior alveolar
      nerve paresthesia, respectively.

PMID- 11526570
TI  - Long-term evaluation of arthroscopic discectomy of the temporomandibular joint
      using the Holmium YAG laser.
AB  - PURPOSE: The goal of this study was to evaluate the clinical results with
      arthroscopic discectomy using a Holmium YAG laser for treatment of patients with
      pain and dysfunction and large disc perforations resulting by advanced internal
      derangement. PATIENTS AND METHODS: The subjects comprised 30 patients (38 joints)
      who underwent arthroscopic discectomy with Holmium YAG laser. All patients had
      chronic pain, restricted range of motion, and a diagnosis of disc perforation
      (Wilkes stage IV to V of internal derangement). All patients had not responded to
      conventional nonsurgical treatment (eg, appliance therapy, nonsteroidal anti
      inflammatory drugs, physical therapy) or previous temporomandibular joint (TMJ)
      arthroscopy. All patients filled out a questionnaire preoperatively and
      postoperatively for assessment of their signs and symptoms. The questionnaire
      consisted of a visual analog scale (VAS) with items on pain and diet. RESULTS:
      The overall success rate for arthroscopy discectomy using a Holmium YAG laser was
      93.33% (28 of 30 patients) in a mean follow-up of 31.7 months. No complications
      were observed in this study. Maximal interincisal opening improved from a mean of
      25.40 to 39.96 mm after 18 months or more from surgery. The subjective data
      elicited from VAS scores showed a significant improvement in pain score, in
      interference of pain with normal diet, and effect of pain on life in general. All
      preoperative scores were significantly different from postoperative scores (P
      <.05). CONCLUSIONS: On the basis of this follow-up study, arthroscopic discectomy
      for treatment of large disc perforations seems to provide an effective treatment
      for TMJ pain and dysfunction, decreasing the pain and improving the range of
      motion.

PMID- 11526572
TI  - Distraction osteogenesis after membranous bone onlay grafting in a dog model.
AB  - PURPOSE: The purpose of this experiment was to study the possibility of
      distraction osteogenesis in a membranous bone onlay graft to the mandible and to
      clarify the histology of the bone repair. MATERIALS AND METHODS: Four dogs, 5
      months of age at the beginning of the experiment, were used for this study. The
      zygomatic arch was exposed in the subperiosteal plane, and a 3-cm long, full
      thickness portion of the arch was harvested. The lateral surface of the
      mandibular body was exposed in the subperiosteal plane, and the bone was fixed to
      the lateral surface as a membranous onlay graft using screws. A vertical
      osteotomy through the graft and underlying mandibular body was done
      postoperatively at week 1 in dog 1, week 2 in dog 2, week 3 in dog 3, and week 4
      in dog 4. An external distraction device was applied to the mandibular body, and
      distraction was started 7 days after the operation at a rate of 1 mm/d for 10
      days. After completion of distraction, the device was left in place for 6 weeks
      to allow for bony consolidation. Radiographs were carried out at 2, 4, and 6
      weeks postdistraction. All dogs were killed 6 weeks after distraction. RESULTS:
      New bone between the native underlying mandibular segments was generated in the
      distraction zone in all dogs. New bone was not generated between the segments of
      the membranous bone onlay graft in dog 1, but was generated in dog 2, dog 3, and
      dog 4. However, in dogs 2 and 3, the new bone between the segments was less firm,
      with more fibrous tissue, than the bone between the native underlying mandibular
      segments. Histologically, the distraction gap between the segments of the
      membranous bone onlay graft in dogs 2 and 3 was composed of considerable fibrous
      tissue in the central zone and activated osteoblastic cells forming new bone in
      the margins. In dog 4, there was much more osteoblastic activity in the
      distraction gap, and the new bone had the appearance of almost normal cortical
      bone. CONCLUSION: These findings show that distraction osteogenesis is possible
      in a membranous bone onlay graft and suggest that the distraction should be
      performed at least 4 weeks after the onlay grafting.

PMID- 11526573
TI  - Strength analysis of Le Fort I osteotomy fixation: titanium versus resorbable
      plates.
AB  - PURPOSE: The purpose of this study was to compare the biomechanical
      characteristics of metallic and polymeric fixation systems using a 3-dimensional
      skull model to simulate clinical conditions of maxillary advancement and loading.
      MATERIAL AND METHODS: Standard titanium, prebent titanium, and resorbable plates
      and mesh were applied to surgically altered polyurethane skulls. The constructs
      were loaded using an Instron machine (Instron Inc, Canton, MA) in anterior
      posterior (AP) and inferior-superior (IS) directions. The load displacement, load
      to failure, and deformation magnitudes and modes of failure were recorded.
      Statistical studies included analysis of variance (ANOVA) at P <.05. RESULTS:
      Elastic stiffness was different among groups in the AP direction, but no
      significant difference was found in the IS direction. The IS loading direction
      load displacement (stiffness) was significantly greater than that on AP loading.
      The maximum load for permanent deformation was larger in the AP direction, while
      the maximum load for breaking was larger in the IS direction. CONCLUSION: The
      overall evaluation of the model and test analyses supported the relative value of
      this in vitro system and study procedure. All systems showed load capacity
      magnitudes above 285 N (64 lbs) and more elastic resistance in the IS direction.
      The resorbable systems showed lower elastic stiffness compared with the titanium
      systems, but they appear to be adequate for fixation and withstanding the forces
      of mastication.

PMID- 11526575
TI  - Changes in the inferior alveolar nerve after mandibular lengthening with
      different rates of distraction.
AB  - PURPOSE: This study investigated the changes in the inferior alveolar nerve after
      mandibular lengthening with different rates of distraction. MATERIALS AND
      METHODS: Bilateral mandibular corticotomies were performed in 8 goats. The
      mandibles in 6 goats were lengthened 10 mm using a custom-made distractor with 2
      different rates of distraction (1 mm/d [n = 3] and 2 mm/d [n = 3]); the other 2
      nondistracted mandibles served as a control. The goats with distracted mandibles
      were killed at 2 weeks after completion of distraction. The inferior alveolar
      nerve specimens from all animals were harvested and processed for histologic and
      ultrastructural evaluation. RESULTS: The mandibles were lengthened successfully
      in the distracted animals. Morphologic changes in the inferior alveolar nerves
      were observed when compared with the nondistracted controls. Moreover, signs of
      nerve degeneration, such as demyelination, axonal swelling, axoplasmic darking,
      and decrease in the number of axons, were more extensive and prominent in those
      nerves distracted at a rate of 2 mm/d. CONCLUSIONS: Degenerative changes in the
      inferior alveolar nerve occur after mandibular lengthening by distraction
      osteogenesis. The distraction rate of 1 mm/d appears to be tolerable and safe for
      the inferior alveolar nerve, but rapid distraction may cause serious
      degeneration.

PMID- 11526577
TI  - Disc preservation surgery for the treatment of internal derangements of the
      temporomandibular joint.

PMID- 11526578
TI  - Discectomy for the treatment of internal derangements of the temporomandibular
      joint.

PMID- 11526579
TI  - Large maxillary mass in a child.

PMID- 11526580
TI  - Comprehensive management of cleft lip and palate deformities.
AB  - PURPOSE: The controversy regarding the timing of repair of the deformities
      associated with cleft lip and palate still exists. The goal of this article is to
      present a versatile, universal philosophy of management of these deformities
      involving early repair. PATIENTS AND METHODS: Over 20 years, 2,698 new patients
      with cleft lip and palate deformities were treated. These included 1,298
      unilateral and 320 bilateral cleft lip and palate patients. The remaining
      patients (1,018) had isolated palatal clefts. All patients were operated
      according to the same protocol and the same surgical procedure. The treatment
      philosophy was based on early, wide myoperiosteal-periosteo-sutural
      reconstruction by a modified Delaire functional cheilorhinoplasty and alveolar
      gingivoperiosteoplasty at 3 months, followed by soft and hard functional
      palatoplasty at 9 months. RESULTS: All patients were followed longitudinally and
      retrospectively. The parameters investigated were facial symmetry, presence or
      absence of growth retardation, and oropharyngeal and nasal function. The
      parameters studied indicated that when this treatment schedule was followed and
      the procedures were performed on time and according to the protocol, there was
      minimal growth retardation of the maxilla. When early gingivoperiosteoplasty was
      performed in 25% of the patients there was a sufficient amount of alveolar bone
      for eruption of the primary and permanent dentition. This negated the need for
      secondary alveolar bone grafting. The development of the upper lip was
      harmonious, and usually no further corrective procedures were necessary. The nose
      was usually well developed and functionally normal. CONCLUSION: Optimal
      rehabilitation of the patients was achieved by following the principles and
      treatment strategies described. If the treatment principles are not incorporated
      in the functional repair (ie, joining of the primary and the secondary growth
      centers during corrective procedures), compromised results are to be expected.

PMID- 11526582
TI  - Multifocal desmoplastic fibromas of the mandible.

PMID- 11526583
TI  - Osteochondroma of the mandibular condyle: report of 2 cases treated with
      conservative surgery.

PMID- 11526584
TI  - Outpatient use of low-molecular weight heparin in an anticoagulated patient
      requiring oral surgery: case report.

PMID- 11526586
TI  - Extraoral removal of mandibular odontogenic dentigerous cysts: a report of 2
      cases.

PMID- 11526587
TI  - Surgical and reconstructive treatment of a large ossifying fibroma of the
      mandible in a retrognathic patient.

PMID- 11526588
TI  - Isolated lymphoepithelial lesion of the palate: report of a case and review of
      the literature.

PMID- 11526589
TI  - Condylar resorption following distraction osteogenesis: a case report.

PMID- 11526591
TI  - Bony ossicle in the maxillary sinus containing a tooth.

PMID- 11526592
TI  - The biology of platelet-rich plasma.

PMID- 11526594
TI  - Implications of signal transduction inhibition for the treatment of chronic
      myeloid leukemia.

PMID- 11526595
TI  - The role of Bcr-Abl in chronic myeloid leukemia and stem cell biology.
AB  - Hematopoietic stem cells, the critical target cells in chronic myeloid leukemia
      (CML), are difficult to study owing to their rarity. An in vitro differentiation
      model was used to examine the role of the Bcr-Abl tyrosine kinase in the
      pathogenesis of CML. A tetracycline-regulated promoter was developed to drive Bcr
      Abl expression in differentiating embryonal stem cells. Enforced Bcr-Abl
      expression was sufficient to increase the number of multilineage progenitors.
      Myeloid progenitors were expanded in particular and erythroid development was
      suppressed, consistent with the phenotype of CML. A complementary approach was
      used to investigate the effect of specifically blocking Bcr-Abl-deregulated
      tyrosine kinase activity in transformed cells. For this purpose a fusion
      "escort/phosphatase" was created that binds to Bcr-Abl and effectively inhibits
      kinase activity in vitro and in vivo. Loss of function was demonstrated by growth
      inhibition of bcr-abl-transformed fibroblasts, reacquisition of growth factor
      dependence by Bcr-Abl-expressing hematopoietic cells, and normalization of
      erythroid differentiation in a human CML line. These studies reaffirm the central
      role of stem cell biology in understanding the causes and possible treatments for
      CML, and suggest that direct targeting and inhibition of Bcr-Abl kinase activity
      is a valid therapeutic approach to treating this disease.

PMID- 11526596
TI  - Signal transduction inhibition: results from phase I clinical trials in chronic
      myeloid leukemia.
AB  - The tyrosine kinase inhibitor, imatinib mesylate (Gleevec, Novartis
      Pharmaceuticals Corp, East Hanover, NJ) (formerly STI571) showed significant
      antileukemic activity with minimal toxicity in preclinical studies. Based on
      these data, a phase I clinical trial was conducted in patients with chronic
      myeloid leukemia (CML) who failed other treatment options. Once therapeutic doses
      were attained, 53 of 54 patients (98%) in the chronic phase achieved hematologic
      remissions. With prolonged therapy of 2 to 5 months duration, a growing
      percentage of patients achieved cytogenetic responses. Imatinib mesylate also has
      activity as a single agent in CML blast crisis and in patients with Ph(+) acute
      lymphocytic leukemia (ALL). Although responses tend not to be durable, 20% of
      patients with myeloid blast crisis are in continuous remission for periods up to
      1 year. Ongoing clinical studies are directed at optimizing the use of imatinib
      mesylate.

PMID- 11526597
TI  - Molecular studies in chronic myeloid leukemia patients treated with tyrosine
      kinase inhibitors.
AB  - The tyrosine kinase inhibitor imatinib mesylate (Gleevec, Novartis
      Pharmaceuticals Corp, East Hanover, NJ) (formerly STI571) blocks the
      constitutively activated Bcr-Abl tyrosine kinase that is characteristic of
      chronic myeloid leukemia (CML). Molecular analysis for the presence of residual
      Bcr-Abl-positive cells in patients with a cytogenetic response following
      treatment with imatinib mesylate reveals that some patients have undetectable
      disease using quantitative reverse-transcriptase polymerase chain reaction (RT
      PCR) assays capable of detecting 1 in 10(5) Philadelphia chromosome-positive
      (Ph(+)) cells. To examine whether the leukemia is still Bcr-Abl-dependent in
      patients who have responded to imatinib mesylate but have relapsed, a
      quantitative assay that directly measures enzymatic activity of Bcr-Abl toward
      one of its major signaling substrates has been developed. This assay allows
      monitoring both of the imatinib mesylate sensitivity of patient cells in vitro,
      and of the endogenous inhibition of Bcr-Abl kinase activity during imatinib
      mesylate treatment and relapse. Studies show that imatinib mesylate resistance is
      associated with restored activation of the Bcr-Abl signal transduction pathway in
      the majority of cases, indicating that Bcr-Abl remains a valid target for
      therapeutic intervention. Understanding resistance mechanisms of Ph(+) leukemia
      to imatinib mesylate will allow design of therapies to overcome such barriers to
      efficacy.

PMID- 11526599
TI  - Implications of imatinib mesylate for hematopoietic stem cell transplantation.
AB  - The ability of allogeneic bone marrow or blood stem cell transplantation (SCT) to
      induce long-term remission or cure of chronic myeloid leukemia (CML) is well
      established. However, the use of this treatment is limited by the availability of
      suitable human leukocyte antigen (HLA) identical siblings or matched unrelated
      donors (MUD). As a consequence only a relatively small proportion of CML patients
      are eligible for a transplant, and of these not all are cured. The preliminary
      results of trials using the new Bcr-Abl kinase inhibitor imatinib mesylate
      (formerly CGP57-148B, STI571, Gleevec) to treat CML are very encouraging.
      However, a number of important questions cannot yet be answered: Can imatinib
      mesylate induce durable molecular remissions? Can the drug prolong survival in
      comparison with other nontransplant treatments? and, can it actually cure CML
      patients? Until answers to these questions are available, SCT and use of
      interferon-alfa (IFN-alpha) alone or in combination (perhaps with imatinib
      mesylate) must remain major therapeutic options. I summarize here the advantages
      and disadvantages associated with currently available therapy. I review three
      different approaches to initial treatment of the CML patient diagnosed in chronic
      phase, and make a tentative recommendation for one of these options. It is likely
      that the situation will alter considerably in the foreseeable future.

PMID- 11526598
TI  - Interferon-alfa-based treatment of chronic myeloid leukemia and implications of
      signal transduction inhibition.
AB  - The cytokine interferon-alfa (IFN-alpha) has substantial activity in chronic
      myeloid leukemia (CML) and is the nontransplant standard of care for chronic
      phase disease. When used as front-line therapy, IFN-alpha induces a state of
      tumor dormancy and delays progression to advanced phase. Unfortunately, IFN-alpha
      is associated with substantial toxicity at therapeutic doses. The introduction of
      pegylated IFN-alpha (PEG-IFN-alpha), a modified form of the protein that permits
      weekly administration, may alleviate some of the problems observed with IFN
      alpha. Combination regimens of IFN-alpha with other drugs such as cytarabine (Ara
      C) appear to enhance efficacy and are currently under investigation. The tyrosine
      kinase inhibitor imatinib mesylate (Gleevec, Novartis Pharmaceuticals Corp, East
      Hanover, NJ) (formerly STI571) also is efficacious in chronic-phase CML, with a
      low toxicity profile. However, its potential to cure CML remains unknown even
      though it achieves frequent cytogenetic responses. To enhance treatment outcome,
      a combination of IFN-alpha and imatinib mesylate therapies is proposed. Low-dose
      IFN-alpha may be given after imatinib mesylate-induced remission as a specific
      immune stimulant to consolidate the remission. Recent data showing a possible
      additive effect of imatinib mesylate and IFN-alpha suggest that concurrent use of
      these agents may also be more effective than single use, particularly in advanced
      stages of CML where imatinib mesylate has activity but resistance develops.

PMID- 11526600
TI  - Perspectives on the future of chronic myeloid leukemia treatment.
AB  - Chronic myeloid leukemia (CML) is probably the best understood human malignancy
      at the molecular level, but among the hardest to explain to patients concerning
      appropriate treatment options. At present, we do not know the long-term outcome
      of promising new therapies such as the tyrosine kinase inhibitor imatinib
      mesylate (Gleevec, Novartis Pharmaceuticals Corp, East Hanover, NJ) (formerly
      STI571) and nonmyeloablative transplants. There is also no reliable way to
      predict which patients will respond to a particular therapy. The development of
      methods to predict therapeutic response will be of major benefit to patients, and
      the newly emerging science of gene array analysis may provide such a tool. In
      this context, given the proven likelihood of cure with allogeneic transplantation
      and the negative effects of delay, in Seattle we continue to suggest
      transplantation as the initial form of therapy for patients below age 55 years
      with matched sibling donors. For patients without matched donors below the age of
      40, we would suggest an unrelated donor search and only proceed directly to
      transplant for those with allele-level matches. For younger patients without
      matches and those aged 40 to 55, an initial trial of imatinib mesylate might be
      preferred. For patients over age 55 with CML, initial therapy with imatinib
      mesylate, possibly an interferon-containing regimen or nonmyeloablative
      allogeneic transplantation may be considered.

PMID- 11526601
TI  - Thought Field Therapy: initial research.

PMID- 11526602
TI  - The impact of Thought Field Therapy on heart rate variability.
AB  - Thought Field Therapy (TFT) is a rapid treatment for psychological problems
      typically taking only minutes. HRV has been shown to be a strong predictor of
      mortality and is adversely affected by such problems as anxiety, depression, and
      trauma. Interventions presented in the current literature show modest
      improvements in HRV. Twenty cases, treated by the author and other therapists
      with TFT, are presented. The cases include some with diagnosed heart problems and
      very low HRV, which is ordinarily more resistant to change. The degree of
      improvements that are registered on HRV as a result of TFT treatment exceeds
      reports found in the current literature. There is a close correspondence between
      improved HRV and client report of reduced degree of upset. HRV may prove to be an
      appropriate objective measure of psychotherapy efficacy given the correspondence
      between client report and HRV outcome. Further research in TFT and HRV is
      encouraged by these results.

PMID- 11526603
TI  - Tertullian's motto and Callahan's method.
AB  - The purposes of this commentary are to provide a critique of Callahan's (this
      issue) article on Thought Field Therapy (TFT) and to discuss when our commitment
      to intellectual open-mindedness requires that we attend to nontraditional
      treatment interventions in clinical psychology.

PMID- 11526604
TI  - Raising and lowering of heart rate variability: some clinical findings of Thought
      Field Therapy.
AB  - This clinical report presents some of the findings in Thought Field Therapy (TFT)
      that show both raising and lowering of heart rate variability (HRV). TFT
      algorithms are effective, but the specificity of diagnosed treatment gives
      results that are superior to algorithms. Some TFT treatments take only seconds to
      yield improved results on HRV. Toxins can undo a cured problem and lower HRV. TFT
      can overturn the effect of some toxins. It is hypothesized that TFT works by
      inputting a specific code that addresses and effects the healing system. HRV may
      be a measure of general physical and mental health.

PMID- 11526605
TI  - Heart rate variability does not tap putative efficacy of Thought Field Therapy.
AB  - Callahan (2001) has offered a series of case reports in an effort to validate the
      rationale and methods of Thought Field Therapy (TFT). These case reports employ
      subjective ratings, that is, the Subjective Units of Distress (SUD) rating scale
      as well as a gross measure of heart rate variability (HRV). My criticisms center
      around (a) inappropriately strong inferences given exclusive reliance on case
      reports, a potentially biased sample, and lack of appropriate controls; (b)
      misinterpretation of statistical artifact as systematic effect; (c) lack of
      systematic evaluation of HRV changes; and (d) erroneous interpretation of HRV.
      Callahan's article provides no evidence for the efficacy of TFT nor does it
      provide evidence for the credibility of TFT's rationale.

PMID- 11526606
TI  - Heart rate variability as an outcome measure for Thought Field Therapy in
      clinical practice.
AB  - The need for empirical, objective, clear, and practical outcome measures for
      therapy has long been recognized by clinicians and researchers. Pragmatic tools
      for objective determination of the efficacy of therapy have been scarce in
      clinical practice settings. Heart rate variability (HRV) is increasing in
      popularity for use in clinical settings as a measure of treatment success. Since
      HRV is stable and placebo-free, it has the potential to meet this need. Thirty
      nine cases are presented from the clinical practices of the authors and three
      other clinicians where HRV was used as an outcome measure for Thought Field
      Therapy (TFT). The cases included TFT treatments which addressed a wide variety
      of problems including phobias, anxiety, trauma, depression, fatigue, attention
      deficit hyperactivity disorder, learning difficulties, compulsions, obsessions,
      eating disorders, anger, and physical pain. A lowering of subjective units of
      distress was in most cases related to an improvement in HRV.

PMID- 11526607
TI  - The search for the holy grail: heart rate variability and thought field therapy.
AB  - Thought Field Therapy (TFT) is one of several unusual psychotherapies that have
      witnessed rapid growth over the past few years, despite the absence of scientific
      support. Promoters of TFT frequently cite changes in heart rate variability (HRV)
      as evidence of TFT's effects. Pignotti and Steinberg (2001) present reports of 39
      cases in which HRV was assessed prior to and immediately following TFT. Serious
      methodological shortcomings preclude interpretation of these data with respect to
      either the efficacy of TFT or the clinical utility of HRV. Ethical concerns are
      raised about the aggressive promotion of TFT and the misuse of HRV.

PMID- 11526608
TI  - Thought Field Therapy clinical applications: utilization in an HMO in behavioral
      medicine and behavioral health services.
AB  - Thought Field Therapy (TFT) is a self-administered treatment developed by
      psychologist Roger Callahan. TFT uses energy meridian treatment points and
      bilateral optical-cortical stimulation while focusing on the targeted symptoms or
      problem being addressed. The clinical applications of TFT summarized included
      anxiety, adjustment disorder with anxiety and depression, anxiety due to medical
      condition, anger, acute stress, bereavement, chronic pain, cravings, depression,
      fatigue, nausea, neurodermatitis, obsessive traits, panic disorder without
      agoraphobia, parent-child stress, phobia, posttraumatic stress disorder,
      relationship stress, trichotillomania, tremor, and work stress. This uncontrolled
      study reports on changes in self-reported Subjective Units of Distress (SUD;
      Wolpe, 1969) in 1,594 applications of TFT, treating 714 patients. Paired t-tests
      of pre- and posttreatment SUD were statistically significant in 31 categories
      reviewed. These within-session decreases of SUD are preliminary data that call
      for controlled studies to examine validity, reliability, and maintenance of
      effects over time. Illustrative case and heart rate variability data are
      presented.

PMID- 11526609
TI  - Sakai et al. is not an adequate demonstration of TFT effectiveness.
AB  - Sakai et al. (2001) report an uncontrolled case series of TFT treatments applied
      to a wide range of psychological complaints in a large health maintenance
      facility. They analyze verbal report measures of symptom severity and conclude
      that the specific treatment is effective for a wide range of psychological
      problems. A review of the theory and research on TFT efficacy indicates that the
      theoretical basis for the specific treatment is unfounded and that adequately
      controlled efficacy research has yet to be conducted. The authors' conclusions
      about effectiveness and applicability are not supported by either theory, prior
      research, or the findings of their clinical application.

PMID- 11526610
TI  - Thought Field Therapy-soothing the bad moments of Kosovo.
AB  - Trauma in Kosovo was treated with Thought Field Therapy (TFT) during five
      separate trips by members of the Global Institute of Thought Field Therapy, in
      the year 2000. Clinicians from Sweden, the United Kingdom, and the United States
      were joined in Kosovo by four physicians who transported them to remote war-torn
      villages where patients with severe trauma were treated. Treatment was given to
      105 patients with 249 separate traumas. Total relief was reported by 103 of the
      patients, and for 247 of the separate traumas. Follow-up data averaging five
      months revealed no instance of relapse.

PMID- 11526611
TI  - Between search and research: how to find your way around? Review of the article
      "Thought Field Therapy- soothing the bad moments of Kosovo".
AB  - This article is based on a review of the article, "Thought Field Therapy-Soothing
      the Bad Moments of Kosovo," (Johnson, Shala, Sejdijaj, Odell, & Dabishevici
      [2001]). As it is assumed that it is the intention of the reviewed article to
      prove the effectiveness of TFT, the information given is evaluated in terms of
      how well this goal is attained. However, as a sample description is not provided
      and minimal methodological standards, such as some kind of standardized
      diagnostical procedure, are not met, it is not possible to appraise issues
      central to any empirical study. Furthermore the design of the study is not in
      accordance with the goal of the study, as any control for expectancy effects,
      natural remission, or even a comparison with other successful psychotherapeutic
      procedures is missing. The study provides very limited evidence for the
      effectiveness of TFT.

PMID- 11526612
TI  - "Echo attributions" and other risks when publishing on novel therapies without
      peer review.
AB  - A special series on Thought Field Therapy in the Journal of Clinical Psychology
      provides an opportunity for psychologists to learn about techniques and theories
      outside the mainstream of our field. Unfortunately, by publishing this series of
      manuscripts without meeting the standards of peer review, the Journal also
      provides an avenue for the misuse of its good reputation and the improper
      promotion of untested methods. "Echo attributions" can be made whereby an author
      attributes the source of his own words to the professional journal in which the
      text appears. Historical examples illustrate that such misuse of scientific
      journals and institutions occurs. A formal statement of guidelines is needed to
      instruct authors on appropriate versus unethical representations of their
      publications.

PMID- 11526614
TI  - Contexts and systems in studies of maternal and child health.

PMID- 11526615
TI  - Mothers' evaluation of their caregiving for premature and full-term infants
      through the first year: contributing factors.
AB  - We explored change in mothers' evaluations of their caregiving through the first
      postterm year for full-term infants and for prematurely born, very low birth
      weight infants with a history of lung disease, and we examined the contribution
      to this evaluation of infant, family, and mother conditions. Fifty-four mothers
      of premature infants and 49 mothers of full-term infants evaluated their
      caregiving relationship, performance, and satisfaction at 1, 4, 8, and 12 months
      infant postterm age. In addition, at the same intervals-1, 4, 8, and 12 months
      mothers rated their symptoms of depression, infant responsiveness, and
      satisfaction with help from husband or partner. Positive and negative feeding
      behaviors of mother and of infant were rated from videotapes. Regression
      analysis, which included all rated variables, infant birth maturity/lung health
      status, and number of children in the mother's care, showed that the 1-month
      assessment differed significantly from the assessments at 4, 8, and 12 months.
      All conditions, except for infant birth maturity/lung health status and mother's
      positive feeding behavior, were significantly associated with caregiving
      evaluation. Findings support inclusion of infant, family, and mother conditions
      in a caregiving evaluation model. Infant responsiveness may be particularly
      salient to a mother's caregiving evaluation.

PMID- 11526616
TI  - Biological rhythm development in preterm infants: does health status influence
      body temperature circadian rhythm?
AB  - Twenty-six preterm infants, postconceptional age from 28 to 35 weeks and
      postnatal age approximately 14 days, were included in a study of the development
      of temperature circadian rhythm. Insulated abdominal skin temperature and
      incubator air temperature were recorded continuously at 1-min intervals for 24
      hr. Using cosinor analysis, cycle mesor, amplitude, and acrophase were
      determined. Initial results from regression analysis did not confirm a predicted
      linear relationship between postconceptional age and amplitude; however, dividing
      the sample according to health status into sick (N = 15) and not sick (N = 11)
      groups revealed differing regression models. For not sick infants, amplitude
      increased with postconceptional age (R(2) =.405), whereas no relationship was
      found between postconceptional age and cycle amplitude in sick infants (R(2)
      =.069). These results indicate that healthy preterm infants demonstrate emergence
      of circadian temperature rhythm. Implications include potential time-based
      periods of vulnerability, overheating and hyperthermia, and management of
      incubator operation.

PMID- 11526617
TI  - Developmental outcomes of infants with bronchopulmonary dysplasia: comparison
      with other medically fragile infants.
AB  - The purpose of this study was to compare the developmental outcomes and mother
      infant interactions of infants with bronchopulmonary dysplasia (BPD) and those of
      other medically fragile infants. One-hour behavioral observations were made of
      the interactions of mothers with two groups of infants (23 with BPD, 39 medically
      fragile without BPD or neurological problems) at enrollment, every 2 months
      during hospitalization, 1 month after discharge, and at 6 months' and 12 months'
      corrected age. Assessment of the home environment also was done at 6 and 12
      months. Multiple regressions were calculated separately for child mental,
      adaptive, language, and motor outcomes. Predictors were: home environment
      assessment, measures of maternal interactive behaviors (positive attention,
      expression of negative affect, medicalized caregiving), infant group membership,
      and presence of intraventricular hemorrhage (IVH) in the infant. There were no
      significant differences between the two groups in any of the developmental
      outcomes or interactive variables, and the presence of IVH had no effect on these
      variables. Maternal positive attention and the home environment were correlated
      with mental development, and mother negative affect was related to adaptive
      behavior for both groups. Differences in developmental and interactive behaviors
      between infants with BPD and other prematurely born infants found in other
      studies appear to be a result of chronic health problems and, thus, are not
      unique to infants with BPD.

PMID- 11526618
TI  - Relationship of psychosocial tasks of pregnancy and attentional functioning in
      the third trimester.
AB  - Because childbearing women function in multiple roles, the capacity to focus or
      concentrate is an important resource while preparing for birth and parenting. In
      addition to daily tasks that require mental effort, gravidas have psychosocial
      demands related to pregnancy. The purpose of this study was to examine the
      relationship between the psychosocial tasks of pregnancy and the capacity to
      focus or direct attention. A convenience sample of 57 pregnant women in their
      third trimester was recruited from prenatal education classes to participate in
      this descriptive correlational study. After other variables thought to influence
      attentional functioning were considered, women experiencing the greatest conflict
      in psychosocial tasks had the most difficulty using directed attention and more
      negatively evaluated their attentional functioning. In order to empower gravidas
      to participate in their health care, it is important for researchers and
      practitioners to understand and support directed attentional functioning, an
      important area for nursing care and research.

PMID- 11526619
TI  - Relationships among maternal-fetal attachment, prenatal depression, and health
      practices in pregnancy.
AB  - The purpose of this study was to investigate a conceptual model in which
      depression was proposed to have direct negative effects on positive health
      practices as well as indirect negative effects through maternal-fetal attachment
      (MFA). Participants were 252 adult pregnant women, between 20 and 40 weeks
      postgestation, who were recruited from five prenatal care sites. Data were
      collected using mailed self-report instruments measuring MFA, depression, health
      practices, and demographic and pregnancy information. Hierarchical regression was
      used to examine direct and indirect effects of depression, person characteristics
      (maternal age, pregnancy risk status, parity, ethnicity, education, income,
      marital status), and MFA on health practices. Results of the study supported the
      conceptual model. Higher education, lower parity, and being partnered predicted
      more positive health practices (p <05). After controlling for person
      characteristics, depression was found to be a significant predictor of MFA. Both
      depression and MFA were significant predictors of positive health practices but
      in opposite directions. Depression had a negative relationship and MFA a positive
      relationship with positive health practices.

PMID- 11526621
TI  - Real qualitative researchers do not count: the use of numbers in qualitative
      research.
AB  - Two myths about qualitative research are that real qualitative researchers do not
      count and cannot count. These antinumber myths have led to the underutilization
      of numbers in qualitative research and to the simplistic view of qualitative
      research as non- or antinumber. Yet numbers are integral to qualitative research,
      as meaning depends, in part, on number. As in quantitative research, numbers are
      used in qualitative research to establish the significance of a research project,
      to document what is known about a problem, and to describe a sample. But they are
      also useful for showcasing the labor and complexity of qualitative work and to
      generate meaning from qualitative data; to document, verify, and test researcher
      interpretations or conclusions; and to re-present target events and experiences.
      Although numbers are important in the treatment of qualitative data, qualitative
      researchers should avoid the counting pitfalls of verbal counting, overcounting,
      misleading counting, and acontextual counting.

PMID- 11526620
TI  - Development and testing of the patient expectations and satisfaction with
      prenatal care instrument.
AB  - Addressing consumer needs requires the development of a valid means of
      specifically measuring pregnant women's satisfaction with prenatal care. This
      study's purpose was to develop items for, to pilot-test, and to examine the
      structural validity of the Patient Expectations and Satisfaction with Prenatal
      Care (PESPC) instrument. Extant literature and information obtained from focus
      groups were used in the development. The PESPC was pilot-tested with a sample of
      114 pregnant women receiving prenatal care. To structurally validate the PESPC,
      data collected from 587 women who participated in a cross-sectional, self
      administered survey were used. Structural equation modeling and confirmatory
      factor analysis were used to develop and cross-validate the PESPC. The PESPC was
      found to be structurally valid, and the subscales of Expectations and
      Satisfaction demonstrated acceptable levels of internal consistency.

PMID- 11526622
TI  - [Otoacoustic emissions screening as early identification of hearing loss in
      newborns].
AB  - The aim of this study was to examine the results of transient evoked otoacoustic
      emissions (TEOAE) as screening test for hearing impairment in newborn infants. We
      examined 9.951 of 11.405 infants born in our city from January 1st, 1995, to
      December 31st, 1998. A TEOAE test was performed prior to discharge and repeated
      one week later in cases who failed the first TEOAE. In case of suspected hearing
      loss auditory brainstem response (ABR) was performed 3 months later. Hearing loss
      was defined as ABR threshold > 20 dB. 157 infants (1.5%) were identified with
      hearing loss. Screening with TEOAE was sufficiently sensitive in identification
      of congenital hearing impairment and the efficacy increased with the experience.

PMID- 11526623
TI  - [Result of middle fossa vestibular neurectomy in Meniere's disease].
AB  - The results and complications of 224 middle fossa vestibular neurectomies (MFVN)
      performed between 1968 and 1994 are reported. Relief of vertigo, hearing and
      tinnitus (both pre- and postoperative), facial paralysis, wound infection, suture
      dehiscence, cerebrospinal fluid (CSF) leak, meningitis, subdural hematoma,
      average hospitalization time, and death were evaluated. The procedure was
      effective against vertigo in Meniere's disease in 100% of the cases with
      unilateral involvement. The excellent results with regard to relief of vertigo
      and the acceptable incidence of complications make MFVN one of the most adequate
      surgical treatments for Meniere's disease.

PMID- 11526624
TI  - [Obstructive sleep apnea in children. Our experience].
AB  - We expose our experience in obstructive sleep apnea syndrome (OSAS) in the
      pediatric population and review the literature. Forty-six nocturnal respiratory
      polygraphies were performed using a portable device (Eden Trace II Plus) that
      measures heart rate, chest wall impedance, nasal/oral airflow and oxygen
      saturation. Seven children have been studied before and six weeks after
      Adenotonsillectomy. All this children experienced an immediate and important
      improvement of their obstructive symptoms. After Adenotonsillectomy the number of
      obstructive sleep apneas disminished up to 87.25% and the number of hypoapneas
      disminished up to 73.3. The arterial oxygen saturation during the night
      normalized in the seven patients. The initial treatment of OSAS in children
      should be the Adenotonsillectomy, although the diagnostic criteria of OSAS in
      children have to be defined more precisely in the future.

PMID- 11526625
TI  - [Auditory training with wide-band white noise: effects on the recruitment (III)].
AB  - The auditory training with wide-band white noise is a methodology for the
      qualitative recovery of the hearing loss in people suffering from sensorineural
      hearing loss. It is based on the application of a wide-band white modified noise.
      In a prospective study, we have assessed the modifications of the recruitment
      coefficient in a sample of 48 patients who have followed a program of 15 auditory
      training with wide-band white noise sessions. The average improvement of the
      recruitment coefficient expressed in percentage is a 7.7498%, which comes up to
      23.5249% in the case of a binaural recruitment coefficient. From our results, it
      can be deduced that the auditory training with wide-band white noise reduces the
      recruitment. That is to say, the decrease of the recruitment in high intensities
      both binaurally and in all ears.

PMID- 11526626
TI  - [Distant metastases in patients with advance laryngeal carcinoma].
AB  - Patients with advanced stage cancer larynx have a higher risk of development of
      distant metastases which means a bad prognosis. In our study we try to identify
      risk factors with the idea of involve to all of these patients in more aggressive
      systemic therapy protocols. Data of 57 patients surgically treated, with squamous
      pharyngolaryngeal carcinoma, stage III and IV, are evaluated. Advanced T stage or
      more extensive neck disease more often caused distant metastases (p < 0.05), and
      also the histological evidence of tumor invasion in three or more cervical nodes
      (p = 0.02), and poorly differentiated tumors (p < 0.05). Tumor site, surface area
      in cm, presence of ulceration, and loco-regional uncontrol were not associated
      with distant metastases.

PMID- 11526627
TI  - [Electrooculographic findings in patients with neurofibromatosis].
AB  - Neurofibromatosis are frequent genetic syndromes, with the electrooculographic
      examination (EOG) as an useful tool in their evaluation. We present the EOG
      findings of 16 patients with this entity which were seen at our Department
      between 1969 and 1991. Mean of age was 31 years. Nine patients were female (56%).
      The most frequent pathologic findings were: spontaneous nystagmus (37.5%) and
      abnormalities in the pursuit tracking test (31.2%). These results are discussed
      and the main literature concerning this matter is reviewed.

PMID- 11526628
TI  - [Repair of facial nerve gaps with cryopreserved allografts in rats
      immunosuppressed with cyclosporin A].
AB  - The aim of this study is to assess the feasibility of peripheral nerve allografts
      pretreated utilizing cold storage and cyclosporin A to improve the facial nerve
      regeneration in Wistar rat. Three groups were designed: Normal Wistar rats. 4
      millimeters nerve gaps repaired with cryopreserved nerve allografts. 4
      millimeters nerve gaps repaired with cryopreserved nerve grafts and treated with
      cyclosporin A. At 16 weeks post-engraftment the animals were evaluated: Facial
      palsy grading system. Electrophysiologic latency. Axonal counting. Nervous fiber
      area immediately distal to the graft. The facial function of the experimental
      groups was similar to the control rats while the latency and morphometric
      parameters was poor than the normal rats. CONCLUSIONS: 1. Cryopreserved nerve
      allografts in facial nerve repair in rats are useful in the aquisition of a
      facial functional nerve recovery as much in immunosuppressed animal as not. 2.
      Cryopreservation of nerve allografts results a good method of storage of nerve
      grafts. 3. Cyclosporin A immunosuppression improved not much the grading facial
      palsy in this model but the electrophysiologic and morphometry is significantly
      better.

PMID- 11526629
TI  - [Alterations of the basal membrane in middle ear cholesteatoma].
AB  - Cholesteatoma epithelium is characterized by a keratinocyte disregulation
      accompanied by destruction of the ossicles and other bony parts of the temporal
      bone. Immunohistochemical methods using antibodies to fibronectin, tenascin and
      metalloproteinases were used to assess the alterations of the instrinsic and
      extrinsic components of the basement membrane. Spatial orientation of the
      basement membrane was preserved in histological sections. Collagen type IV,
      tenascin, fibronectin, basic fibroblastic growth factor (bFGF), and matrix
      metalloproteinases (MMPs) are related to the matrix, perimatrix of normal or
      pathological tissues. They were studied immunohistologically in twenty
      cholesteatomas, eight samples of normal auditory canal skin, and six specimens of
      normal middle ear mucosa. Cholesteatomas displayed alterations of the basal
      membrane, with presence of MMPs and a linear immunoreactivity for collagen type
      IV and laminin, disrupted in areas with intense inflammation. The electronic
      microscope revealed protrusions, duplications, thickening and disruptions of the
      lamina densa of the basement membrane. Thus, we conclude, that MMPs and bFGF
      could play an important role maintaining the proliferative activity and the
      aggressive behaviour of cholesteatoma in the middle ear.

PMID- 11526630
TI  - [Morphological changes in adenotonsillar tissue as early manifestation of
      asymptomatic HIV patient].
AB  - The HIV virus induces in the host several changes in your immunological system,
      which heads to the AIDS. We report two cases diagnosed by pathological studies
      after adenotonsilectomy for adenotonsilar hypertrophy. The diagnosis of HIV
      patients is suspected by epidemiologic (risk groups) or clinical features
      (opportunist diseases). But, it exists a early diagnosis, the histological
      findings in the extranodal lymphoid tissues, unusual on the literature. These
      phenomenons re-enforce the contamination way by means of the superior
      aerodigestive tract mucosis.

PMID- 11526631
TI  - [Benign paroxysmal positional vertigo secondary to surgical maneuvers on superior
      maxilla].
AB  - The benign paroxysmal positional vertigo (BPPV) is a common vestibular end organ
      disorder. BPPV may be idiopathic or secondary to head traumas, viral
      labyrinthitis, otology surgery and many others conditions. We report two cases of
      BPPV secondary to surgical maneuvers on superior maxillary. We have not found
      this etiology in scientific literature but, the increase of this kind of surgery,
      can produce an increase of its frequency. For this reason the otoneurologists and
      oral surgeons must bear in mind this possibility to make a right diagnostic and
      treatment of the syndrome.

PMID- 11526632
TI  - [Langerhans's cell histiocytosis in otorhinolaryngology].
AB  - Langerhans's cell histiocytosis (LCH) is an uncommon disease characterized by an
      accumulation of abnormal histiocytes, together lymphocytes and eosinophils in
      various organs and tissues. The head and neck are frequent sites of initial
      presentation. We present two cases of LCH with otorhinolaryngologic symptoms.
      Current recommendations for diagnosis, evaluation and treatment of LCH are also
      discussed.

PMID- 11526633
TI  - [Modification in subtotal laryngectomy with epiglottoplasty].
AB  - We describe the modification in one of the passages of the technique of subtotal
      laryngectomy with epiglottoplasty, consisting of the opening of larynx through
      the thyroid membrane. This maneuver improves the visualization of the tumor
      facilitating the time of its removal and later reconstruction.

PMID- 11526634
TI  - [Variability of N in Meniere's disease].
AB  - Intratympanic treatment of incapacitating vertigo in Meniere's disease has become
      a first option treatment for most otolaryngologists nowadays. Reporting their
      results following adequate minimum follow-up and under the same criteria is as
      important as to clearly state the indications that have been settled, through
      adequate handicap psychometric tests. Furthermore, when results are reported,
      knowing the total number of patients (N) with a diagnosis of Meniere's disease is
      essential to evaluate such results in those treated patients, bearing in mind
      that most Meniere's patients do well with medical treatment as well.

PMID- 11526635
TI  - [Basophils from palatine tonsils and adenoids in recurrent acute adenoid
      tonsillitis and adenoid tonsillar hypertrophy in children].

PMID- 11526636
TI  - Histological changes in the nerve, skin and nasal mucosa of patients with primary
      neuritic leprosy.
AB  - Primary neuritic leprosy (PNL) presents as a peripheral neuropathy with no
      visible skin patches and skin smears negative for acid fast bacilli. The
      pathogenesis of PNL is poorly understood. The aim of the study was to document
      the histological changes in the nerve, apparently normal skin and nasal mucosa in
      PNL and to study its significance to the pathogenesis of leprosy lesions. The
      study is based on a cohort of 208 PNL patients registered at the Schieffelin
      Leprosy Research and Training Centre, Karigiri. All patients had a nerve biopsy,
      196 had a skin biopsy and 39 had a nasal mucosal biopsy. The findings reveal that
      PNL patients exhibit a spectrum of disease histologically in the nerve ranging
      from lepromatous to tuberculoid leprosy with a significant proportion (46%)
      manifesting a multibacillary leprosy histology. Findings in the apparently normal
      skin and nasal mucosa reveal that there are widespread changes due to leprosy in
      tissues such as the skin and nasal mucosa even when the disease appears
      clinically confined to a few nerves. PNL may be an early stage in the
      pathogenesis of the disease before the appearance of skin lesions. The number of
      nerves enlarged and lepromin status did not give any clue to the nature of
      underlying disease.

PMID- 11526637
TI  - [Leprosy surgery in a bush hospital in Africa: experience in Madagascar].
AB  - We report our experience of leprosy surgery in terms of feasibility and efficacy
      in a small hospital of bush in Madagascar during the period of September 1989 to
      January 1993. Operations of neurolysis, corrections of claw hands by the
      techniques of Lasso-Zancolli or Van Droogenbroeck, arthrodesis, resections and
      amputations have been performed. Our results suggest that at least a part of
      these surgical procedures may be performed by a non specialized medical team,
      taught on the premises. Thus, the cost of treatment will be low and accessible to
      more leprosy patients.

PMID- 11526638
TI  - [Leprosy surgery: retrospective study in Madagascar].
AB  - Leprosy is endemic in Madagascar and the diagnosis of leprosy is still done
      lately. Thus, many patients suffer from multiple and/or severe disabilities.
      Since a long time, many leprologists argue that surgery is necessary and useful
      in the treatment of these disabilities. We report the results of a retrospective
      study done in 25 patients reevaluated 2 to 7 years after surgery. Of these
      patients: 17 patients (68%) have success, 7 patients (28%) have a partial
      improvement and only 1 case (4%) had no benefit. These results are encouraging
      and suggest that surgery must be proposed more often to treat in leprosy
      disabilities.

PMID- 11526639
TI  - Progression of acral bone resorption in multibacillary leprosy.
AB  - Although leprosy became a curable disease after implementation of the Global
      Strategy for the Elimination of Leprosy (WHO), mutilations and deformities are
      still commonplace in endemic countries. Hence, it remains important to evaluate
      the prevalence rate and the risk factors of acral bone resorption in the
      multidrug therapy (MDT) era. A cohort of 105 newly-diagnosed adult multibacillary
      leprosy patients admitted for treatment between 1990-1992 was surveyed until
      1999. Progression of bone resorption (BR) in cured leprosy patients was observed
      up to 8 years after release from MDT. Twenty three percent of the patients were
      found to have acral resorption. BR was found to be associated with male sex,
      grade of disability at diagnosis with other deformities and with the occurrence
      of four or more lepra reactions. Patient surveillance after release from MDT
      continues to be a necessary procedure in individuals with disabilities and
      recurrent or persistent reactions.

PMID- 11526640
TI  - Presence of cytokines in the serum may affect the in vitro responses of T cells.

PMID- 11526641
TI  - [Leprosy situation in the southeastern region of Madagascar from 1996 to 1998].
AB  - Leprosy is endemic in Madagascar. The authors report the results of an
      epidemiologic study performed between 1996 and 1998 in Farafanguna, localized in
      the South-Eastern of the country. During this period, 217 new cases have been
      diagnosed. Of the 130 cases included in the study, 69.23% were children aged
      lower than 15 years and 76.91% suffered from a multibacillary form. More than 50%
      of the cases belonged to a large family (6 persons or more) and at least one
      family case was found in more than 60% of cases. These results enhance the
      severity of the disease in the country and show the presence of multiple risk
      factors (promiscuity, family cases and multibacillary forms).

PMID- 11526642
TI  - [Vestibular and oculomotor changes in subjects treated with cisplatin].
AB  - Cisplatin is an agent used in the treatment of distinct oncologic diseases. We
      present the electrooculographic (EOG) findings of 6 patients which were seen at
      our Department under the diagnosis of chronic toxicity for cisplatin and
      associated vestibular alterations. Mean of age was 45 years. Three subjects were
      female (50%). The most frequent pathologic finding was ataxic pursuit tracking
      (100%). Additionally, spontaneous nystagmus, alterations in positional test, and
      vestibulo-ocular reflex suppression were also found. These results are discussed
      and the main literature concerning this matter is reviewed.

PMID- 11526643
TI  - [Upper lateral cartilage transposition in the surgical management of nasal valve
      incompetence].
AB  - We have operated eight patients with nasal obstruction secondary to internal
      valvular incompetence. In three of them an alar collapse were associated.
      Diagnosis was made by anamnesis and clinical exploration. Open rhinoplasty
      approach was employed. Surgical technique was the transposition of lateral over
      alar cartilage. In the three patients with alar collapse, a fixation graft of
      septal cartilage were added to the previous technique. Nasal obstruction and
      valvular incompetence missapeared in all the patients.

PMID- 11526644
TI  - [Survival rate in epidermoid carcinoma of the oral cavity].
AB  - The present study aims to analyse the survival of 94 patients with squamous cell
      carcinoma of the oral cavity. They were 86 men and 8 women with a mean age of 61.
      Seventy four percent were smokers and 70% consumed alcohol regularly. Eighty
      three percent had unhealthy teeth. A great majority of patients (76) were in the
      advanced stages (III-IV) and 61% showed neck nodules. The overall survival at 5
      years was the following: 70% for patients in stage I, 85% in stage II, 58% stage
      III and only 17% for the patients in stage IV. The most significant prognostic
      factor that affected the survival was the N stage. For the patients in N0 and N1
      we only found significant differences when the lymph nodes were histologically
      affected by the tumor.

PMID- 11526645
TI  - ["Usual" morbidity of pediatric tonsillectomy: a study of 126 cases].
AB  - Pediatric tonsillectomy is a common procedure in the ENT practice, usually in a
      Day-surgery basis. The aim of the present work is to further investigate
      postoperative morbidity to improve both treatment and quality of assistance. 126
      children operated in our Day-surgery unit were included in the study, and a
      questionnaire with items related to postoperative pain, otalgia, halitosis,
      vomitig, fever and other aspects was filled by their parents or relatives in
      charge. Significative pain lasting until the third or fourth day was recorded in
      half of the cases. At the end of the first week most of the children are
      improved, although only 55% are eating normally. Vomitting, usually the day of
      the surgery, is described by one third of cases. In our experience, ambulatory
      tonsillectomy is a safe procedure with low incidence of complications, which are
      mild. However, the delay in returning to a normal diet and the relative high
      incidence of vomiting bring into question the inclusion of tonsillectomy in a Day
      Surgery program, making necessary to implement treatment protocols to avoid such
      problems.

PMID- 11526646
TI  - [The usefulness of craniocorpography in the diagnosis of patients with dizziness
      and increasing muscle tension in the neck].
AB  - By the moment, craniocorpographic record of the Romberg test has been scarcely
      used in clinical practice. Since craniocorpography is a method for recording
      oscillations of the head and shoulders, it can show characteristic patterns in
      patients with vertigo caused by increased muscle tension in the neck. In order to
      confirm this hypothesis, a prospective comparative study was performed with 329
      patients. They were included in three different groups: patients with cervical
      vertigo, patients with vestibular pathology and a healthy control group.
      Movements of the head (with static shoulders) are more usual in patients with
      cervical vertigo (67%) than in those with vestibular pathology (27%) and healthy
      subjects (31%). With regard to the kind of head oscillations, front-back flexions
      and oscillations in all directions were the most frequent (36% and 34%,
      respectively). Nevertheless, the only movements previously reported (cervical
      rotation or torsion) only were 3% of total head movements in our study. We
      concluded that static craniocorpography is an useful method in diagnosing vertigo
      secondary to increased muscle tension in the neck.

PMID- 11526648
TI  - [Auditory training with wide-band white noise: effects on the pain threshold and
      pure tone thresholds].
AB  - The auditory training with wide-band white noise is a methodology for the
      qualitative recovery of the hearing loss in people suffering from sensorineural
      hearing loss. It is based on the application of a wide-band white modified noise.
      In a prospective study, we have assessed the modifications of the total auditory
      threshold (UAt), the conversational auditory threshold (UAc), and the pain
      threshold (Ud) in a sample of 48 patients, who have followed a program of 15
      auditory training with wide-band white noise sessions. The average improvements
      of the variables expressed in percentage are 0.78% for the UAt, 0.64% for the
      UAc, and 5.31% for the Ud. From our results, it can be deduced that the auditory
      training with wide-band white noise does not modify the pure tone thresholds, but
      it moves the pain threshold towards higher intensities, enlarging the dynamic
      auditory field.

PMID- 11526647
TI  - [Congenital lesions of the naso-frontal midline].
AB  - Dermoids cysts, gliomas and encephaloceles are uncommon congenital lesions that
      result from an aberrant embryologic development. Six cases of these nasal lesions
      have been treated. These may present an intracranial extension as a consequence
      of an unusual closure of the anterior neural tube and it requires an early
      diagnosis to avoid local and intracranial infectious complications. Therefore, an
      early surgical correction is thus imperative. Neuroimaging studies may help to
      predict intracranial involvement.

PMID- 11526649
TI  - [Usefulness of facial nerve monitoring during parotidectomy].
AB  - OBJECTIVE: To analyse the usefulness of facial nerve monitoring by continuous
      electromyography during parotidectomy. PATIENTS AND METHODS: Fifty-two
      consecutive patients who underwent parotidectomy (27 unmonitored and 25
      monitored) between 1987 and 1998. Both groups had a similar distribution of
      superficial and total parotidectomy. RESULTS: Facial nerve monitoring reduced the
      incidence and severity of facial nerve paralysis independently of the kind of
      surgery performed. The incidence of temporary facial paralysis was significantly
      lower in the monitored group (36%) than in the unmonitored group (70%) (p =
      0.013). The rates of permanent deficit were 4% for the monitored group and 30%
      for the unmonitored group (p = 0.025). CONCLUSIONS: The results suggest that
      intraoperative facial nerve monitoring reduces the incidence of postoperative
      facial deficit. The routine use of facial nerve monitoring is controversial.
      However, it is considered useful in surgery where there is a higher risk of
      injury to the facial nerve such as total parotidectomy, re-interventions or
      chronic inflammatory conditions.

PMID- 11526650
TI  - [Melanoma of the hard palate].
AB  - Oral melanomas are extremely rare and occur most often on the palate and gingiva.
      Its prognosis is poor. Surgical management remains the preferred treatment,
      sometimes in combination with chemotherapy. We report the case of a 72 years old
      woman with a malignant melanoma of the hard palate who developed three years
      later a gingival nevi and 5 years later metastatic cervical lymph nodes. Our
      treatment has been only radical surgery all times.

PMID- 11526651
TI  - [Parotid metastases of a neuroendocrine cutaneous carcinoma].
AB  - A case of metastatic Merkel-cell carcinoma to lymph nodes on the left side of the
      neck nad left parotid is described. Neuroendocrine cutaneous carcinoma, also
      called Merkel cell carcinoma (MCC), is an uncommon primary skin tumor most often
      seen in elderly. Literature is reviewed and comment about more important features
      of these lesions, like differential diagnosis, prognosis and treatment.

PMID- 11526652
TI  - [Jugular vein thrombosis: report of six cases].
AB  - Venous thrombosis in superior extremities and neck represent less than 5% of the
      total of venous thrombosis. Internal jugular vein thrombosis is associated with
      intravenous drug abuse, long term venous catheterization, local infection or
      spontaneous occlusion. The clinical findings are cervical swelling, progressive
      inflammatory signs overlying sternomastoid muscle, and an important functional
      limitation. Diagnosis is confirmed by cervical ultrasounds and contrast-enhanced
      computer tomography. Usual treatment involves anticoagulation and antibiotics,
      surgery is not frequently needed. We described the management and outcome of six
      cases of internal jugular vein thrombosis.

PMID- 11526653
TI  - [Oat-cell carcinoma of the tongue: report of a case].
AB  - We present a case of oat cell carcinoma of tongue in a 76 year old man with a
      squamous carcinoma of lung.

PMID- 11526654
TI  - [Co-administration of histamine H1 antagonist and oral anticoagulants].
AB  - Indications for oral anticoagulation and antihistamine H1 antagonists therapies
      are increasingly. So, it is easy to find individuals who need both treatments.
      The unknowledgement about possible interferences of antihistamines over
      acenocumarin often makes to avoid them at the same time. A review on a population
      receiving anticoagulation on a Therapeutic Center allowed us to verify disorders
      secondary to the association of antihistamines into their therapeutic scheme.
      Loratadine, ebastine and cetirizine show similar records of interaction into
      acenocumarin pharmacokinetics, probably due to a liver enzymatic induction on the
      anticoagulant drug, producing a decrease on INR values in which anticoagulation
      is measured. This could make necessary to increase temporally acenocumarin dose.
      During coadministration no thromboembolic event nor bleeding were registered.

PMID- 11526655
TI  - [PCI or thrombolysis in myocardial infarction? Effect of the combination of the
      two methods should be studied].

PMID- 11526656
TI  - [Primary PTCA or thrombolysis in acute myocardial infarction?].
AB  - In acute ST-elevation infarction two different reperfusion strategies-
      thrombolytic medication and acute coronary angiography--have proved to improve
      the prognosis. The clinical course for patients with ST-elevation infarction is
      described in relation to whether they received thrombolytic medication or
      underwent acute coronary angiography with the aim of mechanical
      revascularization. The one-year mortality was high (20 percent) regardless of
      treatment strategy. In terms of morbidity there were no clear differences between
      the two treatment groups.

PMID- 11526657
TI  - [A controlled trial with prolonged follow up: percutaneous intervention in acute
      myocardial infarction is equivalent to thrombolytic therapy].
AB  - Previous studies comparing percutaneous coronary intervention (PCI) with
      thrombolysis for treatment of myocardial infarction with ST-elevation have in
      meta-analyses but not in randomized trials shown that PCI is more effective.
      Despite a large volume of primary PCI performed in Sweden no controlled trials
      have been carried out. The present study included 96 patients with myocardial
      infarction with ST-segment elevation treated with primary PCI 1995-1998. The main
      indications were shock (15 cases), contraindication to thrombolysis (24 cases),
      as an alternative to thrombolysis (57 cases), with a mortality in the respective
      groups of 67, 25 and 10 percent. Controls matched for age and infarct location
      and treated with thrombolysis could be identified for 55 of the patients treated
      with PCI. After four years 40 percent and 52 percent of the patients treated with
      PCI and thrombolysis respectively reached the combined endpoint of
      death/myocardial infarction/revascularization/angina pectoris (not significant).
      In conclusion, the study shows that primary PCI in patients with myocardial
      infarction with ST-segment elevation can be performed safely also in Sweden.

PMID- 11526658
TI  - [Vibrio vulnificus. A marine bacterium with lethal potential].
AB  - Vibrio vulnificus is a halophilic gram-negative rod widespread in the aquatic
      environment and associated with primary septicemia and severe wound infections.
      The first Swedish case was reported in 1994. Ever since, sporadic cases have
      occurred in the south of Sweden whenever the coastal water temperature has
      exceeded 20 degrees C. Critical for a successful outcome in these infections has
      been early diagnosis with appropriate antibiotic and surgical treatment. A review
      of this subject was prompted by two cases of fulminant septicemia, which both
      presented themselves as atypical erysipelas.

PMID- 11526659
TI  - [Idiopathic thrombocytopenia during pregnancy. The risk in connection with
      umbilical blood sampling is probably greater than the benefit].
AB  - Some fetuses whose mothers have idiopathic thrombocytopenic purpura (ITP) may
      themselves have low platelet count and are thought to be at risk of serious
      bleeding complications, especially intracranial bleeding, during vaginal
      delivery. The aim of the present study was to prospectively evaluate outcome for
      mothers with ITP and their neonates with or without the information provided by
      percutaneous umbilical blood sampling (PUBS). Our intention was to perform
      cordocentesis using PUBS to measure fetal platelet count in pregnant women with
      ITP, utilizing the information thus derived as an aid in planning for delivery.
      Thirty-five pregnancies in 34 women with ITP or low platelet count (< 105 x
      10(9)/L) were monitored. PUBS was to be performed on 13 women only, five of whom
      were splenectomized. There were two complications related to the PUBS itself
      which led to cesarean sections on the same day. Twelve of the 13 fetuses with
      PUBS had platelet count greater than 50 x 10(9)/L in the 36th week of pregnancy,
      and vaginal deliveries were initially planned. After experiencing one serious
      complication with PUBS, we found it difficult for ethical reasons to perform PUBS
      on mothers with ITP. Therefore 22 pregnancies were monitored without PUBS. Nine
      of the 35 children (26%) were delivered by cesarean section. The frequencies of
      vaginal and cesarean deliveries in the groups with and without PUBS were the
      same. Six of 15 neonates (40%) born to splenectomized mothers had platelet counts
      less than 50 x 10(9)/L during the first days of life and four of these were
      treated with intravenous gamma globulin and/or cortisone. No intracranial
      bleeding was observed in any of the children. In our hands, PUBS in ITP is
      potentially harmful and must be questioned. The frequency of low platelet count
      and/or bleeding complications in neonates of mothers with ITP born vaginally is
      low. In our opinion, the mode of delivery should be chosen mainly on the basis of
      obstetric criteria.

PMID- 11526660
TI  - [Pregnant women's sick leave is behind the increased sick leave among women of
      fertile age. A study of pregnant women's sick leave 1978-1997].
AB  - Sick leave rates among pregnant women have been found to vary substantially over
      time. 8,884 woman delivered at Linkoping and Varnamo Women's Clinics in 1978,
      1986, 1988, 1992, 1995 and 1997 were studied. Sick leave nearly doubled between
      1978 and 1986, and dropped back to the 1978 level in 1997. The somewhat
      paradoxical findings in our surveys indicate that attitudes, especially as
      observed in the youngest age groups, together with a sensible adaptation to the
      prevailing terms of the social security system, may well be the most plausible
      explanation. Studies on sick leave among women of fertile age should preferably
      also contain information on the proportion of sick-listed pregnant women, as a
      small proportion of pregnant women may have a profound impact on sick leave
      statistics among all insured women of fertile age.

PMID- 11526661
TI  - [An inquiry among medical students. No to legalization of euthanasia, but yes to
      dropped charges or remission of sentence].
AB  - In a questionnaire to medical students in Sweden, only 6 out of 135 answered that
      they wanted voluntary active euthanasia to be legalized. However, most of the
      students were of the opinion that the charges brought against the physician could
      be withdrawn pending assessment by a public prosecutor (55), or alternatively,
      that remission of sentence could be granted pending assessment by a court (45). A
      somewhat smaller group (26) answered that prison corresponding to the sentence
      for manslaughter was reasonable. Only 3 students considered voluntary active
      euthanasia to be murder. Legal monitoring of each case of active euthanasia was
      very important to these medical students, but many answered that under specific
      conditions there should be no punishment.

PMID- 11526663
TI  - [Psychologists at community health centers provide emergency crisis intervention.
      The number of referrals to psychiatric departments can be reduced].

PMID- 11526662
TI  - [Both a healthy and an injured brain is shaped and reshaped during the whole
      life. New therapeutic strategies in pediatric neurology, neurology and hand
      surgery].

PMID- 11526664
TI  - [Psychosocial survey of drunken drivers within the KAPUBRA project. A new
      interview technique suitable for matching the right treatment with the right
      client].
AB  - Three different programs for individuals convicted of drunken driving are being
      evaluated in a randomized design in collaboration between researchers at the
      Karolinska Institute and the Prison and Probation Service in Sweden. In the years
      1996-1998, 912 clients were interviewed by means of a structured interview, the
      Addiction Severity Index (ASI), which covers seven problem areas (medical status,
      alcohol use, employment status, drug use, legal status, family/social and
      psychiatric status). So far about half of the subjects have been re-investigated
      two years after leave. Initially, the group being investigated had problems
      particularly in the areas of criminality and alcohol use. Two years later a
      positive trend in most of the problem areas could be observed for clients in
      follow-up.

PMID- 11526665
TI  - [Carefully prepared follow-up of psychiatric patients after discharge is
      necessary to prevent suicide].

PMID- 11526666
TI  - [Organ and tissue donation. Relatives and personnel tell about experiences and
      agony].

PMID- 11526667
TI  - [Questionable sanction by the HSAN counteracts openness in health care].

PMID- 11526668
TI  - [Evidence-based medicine: many critics misunderstand EBM].

PMID- 11526669
TI  - [A welcome debate on evidence-based medicine].

PMID- 11526670
TI  - [Cooling dilates carotid artery].

PMID- 11526671
TI  - [Smoking cessation or lung cancer screening--an artificial antagonism].

PMID- 11526672
TI  - [Sure, the physician should be responsible for the computer systems].

PMID- 11526673
TI  - [Medical decisions at the end of life--practice and attitudes].

PMID- 11526674
TI  - [Whiplash injuries are badly investigated].

PMID- 11526675
TI  - [Listen to citizens' wishes!].

PMID- 11526676
TI  - [STDs today: risk groups and prevention tools].
AB  - The importance of specific programs for controlling and preventing sexually
      transmitted diseases (STD) has been widely recognized, considering that there
      exists no treatment that results in complection resolution of sexually
      transmitted viral pathologies, that many STDs have long periods of infectivity
      and clinical latency, and that there is a high risk of sequelae and of related
      oncogenesis. However, STD prevention can be quite complex, in that a variety of
      diseases with diverse clinical and epidemiological characteristics are currently
      defined as "STDs". One of the main aspects of STD prevention is the
      identification of population groups considered to be at risk of transmission and
      that play an important role in maintaining the current epidemic status of STDs in
      the general population (i.e., sexually promiscuous persons). As with other
      diseases, the prevention of STDs is generally classified into primary prevention
      and secondary prevention. Primary prevention consists of protecting healthy
      individuals from acquiring the infection and mainly consists of promoting safe
      sex (including barrier methods), performing vaccination, and conducting
      information and education campaigns. The objective of secondary prevention is to
      prevent the disease from further evolving in persons who are already infected or
      ill, including the prevention of complications, by providing proper medical care
      and treatment. The main tools of secondary prevention of STDs are: early
      diagnosis of cases, early and targeted therapy, and management of sexual
      partners.

PMID- 11526677
TI  - [Research on endometrial heat shock protein 60 KDA in the study of female
      infertility].

PMID- 11526678
TI  - [Mycoplasma genital infections].

PMID- 11526679
TI  - [Gestational success in patients at risk of preterm labor with presence of
      ureaplasma urealyticum in cervico-vaginal secretions].

PMID- 11526680
TI  - [Ureaplasma urealyticum urogenital infections and assessment of antibiotic
      resistance].

PMID- 11526681
TI  - [Prenatal diagnosis and treatment of congenital toxoplasmosis: a program of
      regional surveillance].
AB  - Toxo-net is a regional program of survey on congenital toxoplasmosis which has
      two aims: 1) to estimate the incidence of gestational and congenital
      toxoplasmosis in our Region (Piemonte); 2) to assess the compliance to our
      diagnostic, therapeutic and follow-up protocols which are thoroughly described.
      Thirty-two obstetrical, neonatal and laboratory units of Piemonte Region have
      been involved. During 18 months (January 1997-June 1998) 365 pregnant women were
      studied because of suspected seroconversion: in 129 patients infection was
      confirmed. Amniocentesis for prenatal diagnosis was carried on 11 patients; two
      fetuses were affected. 35% of the mothers were untreated or inadequately treated.
      Hydrocephaly was observed in two fetuses. Neonatal follow-up at 12 months is
      available for 68 of the 129 infected mothers. Four babies (5.8%) were infected,
      three of them being symptomatic; their mothers had not been treated. It is
      concluded that the implementation of a screening program for toxoplasmosis during
      pregnancy seems to be beneficial. However an effort to improve the surveillance
      system and the education of the gynecologists, general practitioners and of the
      patients is needed, and economic evaluations are warranted.

PMID- 11526682
TI  - [Bacterial synergy in postsurgical infective complications in gynecology].

PMID- 11526683
TI  - [Clinical features of postsurgical infections in obstetrics and gynecology].

PMID- 11526684
TI  - [Sexually transmitted diseases and HIV-1 infection in Italian adolescents].
AB  - OBJECTIVE: To assess the distribution of specific sexually transmitted diseases
      (STD), including HIV-1 infection, among Italian adolescents with an acute STD and
      to evaluate these individuals behavioural characteristics. METHODS: The database
      of Italy's STD Surveillance System was used as the source of data. Data on all
      STD cases reported among individuals under 20 years of age were analysed.
      RESULTS: From September 1990 to December 1997, 57,046 cases of STDs were reported
      to the surveillance system; 1,757 (3.1%) of these were reported among
      adolescents, of whom 896 (51.0%) were males. The most commonly reported diseases
      among males were genital warts (30.7%) and non-gonococcal urethritis (18.5%);
      among females, the most commonly reported diseases were non-gonococcal vaginitis
      (39.1%) and genital warts (30.0%). Of the 555 males tested for HIV-1 antibodies,
      28 (5.0%) were seropositive; of the 510 females tested, 17 (3.3%) were
      seropositive. The highest HIV-1 seroprevalence rates were found among intravenous
      drug users (IDU) (33.3% among male IDUs and 23.8% among female IDUs) and among
      homosexual males (17.6%). DISCUSSION AND CONCLUSIONS: In Italy, the impact of
      STDs among adolescents is not negligible, though the distribution of STDs among
      this population group differs from the distribution among adults. Moreover, the
      prevalence of HIV-1 among adolescents with STDs is similar to that among adults
      with STDs. This study's data suggest the need to further develop STD/HIV
      prevention programmes that specifically target youths.

PMID- 11526685
TI  - [Sexually transmitted diseases in adolescence].
AB  - BACKGROUND: Sexually transmitted diseases (STD) have their most incidence in
      adolescence. We conducted an observational study on the symptomatic patients of
      our STD's office to evaluate epidemiological distribution, behavioral patterns
      and diffusion of genital infections in teen-agers in respect of the adult
      population. METHODS: From april 1996 to april 1999 we studied two groups of
      patients: 54 teen-agers (13-19 years) and 917 women in fertile age (20-40 years).
      All the patients underwent to a clinical and microbiological examination of
      vaginal secretions (Gram slide, wet mount, cultures for bacteria, yeasts,
      eventually Chlamydia trachomatis, Mycoplasma spp, Neisseria gonorrhoeae, Herpes
      simplex virus--HSV--) and to an anamnestic and socio-epidemiological
      questionnaire. RESULTS: The more frequent genital infections among adolescents
      was vulvovaginal candidiasis (35% vs. 23.9% of adult people). HSV was found in
      1.8% of teen-agers (vs. 0.6%) and when requested, Chlamydia trachomatis and
      mycoplasmas was found respectively in 16.6% (vs. 1.1%) and 50% (vs. 28%) in
      adolescents. We observed a high percentage of pregnancy (22.2%) of voluntary
      pregnancy interruption (41.6%) and a specific sexual behavior among teenagers.
      CONCLUSIONS: Our data show a particular behavioral risk pattern in the
      adolescence population and indicate the necessity of a serious program of
      prevention and sexual education that allow young people to live with more
      consciousness and safety their sexuality.

PMID- 11526686
TI  - [HIV occupational infections in gynecology: risk assessment, post-exposure
      management, and drug prophylaxis].
AB  - The average risk of HIV infection after percutaneous exposure to HIV-infected
      blood is 0.3%. Higher risk factors of HIV transmission to health care worker
      after percutaneous exposure are deep injury, visible blood on device, procedure
      involving needle in artery or vein and terminal: Illness in source patient or
      high viremia. It has been shown that post-exposure use of zidovudine diminishes
      risk of transmission. In Italy 5 occupational HIV infections in health care
      workers have been documented. Although prevention of exposure to blood is the
      best method to avoid occupational risk of HIV infection, nevertheless an adequate
      management of blood-borne exposure is essential for achieving a safer health care
      workplace. In this paper we reviewed the modality and the frequency of blood
      borne exposures in Italian health care setting, focusing on in obstetric and
      gynaecology. Finally, Italian recommendation for the management of blood-born
      exposure, including post-exposure chemoprophylaxis are discussed.

PMID- 11526687
TI  - [Screening for HIV-1 infection targeted to women at a center for sexually
      transmitted diseases (STD). Comparison between 2 periods of 5 years of work].
AB  - OBJECTIVE: To determine changes over time in the proportion of individuals
      requesting HIV-1 testing represented by women and in the HIV-1 prevalence among
      women attending a centre for sexually transmitted diseases (STD) in Rome Italy.
      METHODS: We analysed the computerised clinical records of all women undergoing
      HIV-1 testing in two five-year periods (i.e., 1985-89 and 1993-97). RESULTS: In
      the period 1985-89, 2,605 individuals underwent HIV-1 testing; 605 (23.2%) of
      these individuals were women. In the period 1993-97, 5,981 individuals were
      tested; 2,015 (33.7%) were women. When analysing the proportion of women tested
      by exposure category, there was an increase in the proportion of non-drug-using
      heterosexual women (75.5% in 1985-89 vs. 84.6% in 1993-97) and of women from
      geographical areas endemic for HIV (1.8% vs. 5.5%, respectively), where as there
      was a decrease in the proportion of tested women represented by intravenous drug
      users (12.4% vs. 2.7%). Overall, the prevalence of HIV-1 infection among women
      decreased (8.8% in 1985-89 vs. 5.0% in 1993-97). When considering specific
      exposure categories, the prevalence increased among partners of HIV-1 infected
      males (8.7% vs. 36.5%) and among women from endemic areas (2.8% vs. 9.3%).
      DISCUSSION AND CONCLUSIONS: The increased proportion of women requesting HIV-1
      testing, especially those reporting at-risk heterosexual behaviour, suggests that
      women are generally more informed with regard to the risks of sexual
      transmission. However, the increase in HIV-1 prevalence among women with an HIV-1
      infected partner and those from endemic areas suggests that programmes for
      preventing sexual transmission need to be improved.

PMID- 11526688
TI  - [Progress and problems of the treatment of HIV infection].
AB  - The introduction of antiretroviral therapies (ARVTs) with drugs in combination
      has determined a marked reduction in morbidity and mortality in national
      surveillance data bases. A parallel dramatic decrease in HIV plasma viral load
      has been observed. This evidence has been promptly transferred in therapy
      guidelines, in which undetectable viral load is currently considered the primary
      objective of ARVT. However, CD4+ T-cell counts and their trends should not be
      underestimated, particularly as far as their surrogate value and viro
      immunological discordant trends are considered. Last but not least, long-term
      clinical effect of ARVT depends not only on antiviral efficacy, but also on
      toxicity, tolerability, patients' adherence to regimens, resistances and cross
      resistances to anti-retroviral drugs before and during therapy. In conclusion,
      ARVT should be "tailored" both to the stage of the disease and to psycho-social
      profile of the patient, considering of the highest degree of importance, when
      possible, quality of life and preservation of future therapy options.

PMID- 11526689
TI  - Is seborrhoeic dermatitis a clinical marker of HIV disease?
AB  - The Authors have conducted a cohort study on a group of subjects HIV positive,
      asymptomatic, (group A, according to CDC criteria) who presented Seborrhoeic
      dermatitis (SD), to evaluate if this cutaneous finding could be considered a
      marker of the HIV disease. Previously the Authors had shown that healthy subjects
      affected by SD showed at blood level an imbalance in the ratio of PL-PUFA
      (fundamental components of cell walls) to the antioxidants Vitamin E (Vit E) and
      gluthathion peroxidase (GSH-Px); furthermore the Authors reported SD as being
      constantly present in AIDS patients, in which they found more severe biochemical
      changes. On these bases they enrolled 72 HIV positive individuals that presented
      at STD-AIDS Unit of the S Gallicano Institute in the years 1994-1995 and followed
      them, until the 1998. They were all asymptomatic and were divided at the
      beginning in two subgroups, respectively with and without SD. Records were made
      regularly of their clinical, laboratory and biochemical data. The results
      highlighted the fact that SD-HIV positive individuals had severe biochemical
      alterations and a worse clinical evolution (higher incidence of opportunistic
      events). These data confirm on the hand the SD as a cutaneous marker of HIV
      disease not only, but also its presence could indicate the possibility of a worse
      progression of the disease. Finally the Authors suggest the possibility of a
      dietary pharmacological treatment, associated, or not, with antiretroviral
      therapy, to the aim to improve cell membrane defences and thereby cell immunity
      itself.

PMID- 11526690
TI  - [Colposcopy in human papilloma virus infections of the distal uro-ano-genital
      tract].
AB  - HPV infections fall within the STDs and certain high-risk types have a
      significant role in the cancer genesis of the distal genital tract. The infection
      results can be clinically evident or be subclinical and in this latter case they
      are revealed by a highly-sensitive colposcopic examination after acetic acid
      application at 3% followed by Schiller's test with Lugol solution in weak iodine
      concentration. Indeed, the distal districts of male and female uroano-genital
      tracts takes advantage of the colposcopic diagnostics although complementary
      analysis like histology or DNA tests for HPV typing have sometimes to be
      performed to confirm the results or to evaluate the prognosis. HPV subclinical
      lesions, above all at cervical and vaginal level, are those mostly involved with
      the cancer genesis: the bright-white acidophilia often combined with irregular
      surface, atypical vascularization and discrete iodine caption represents a
      colposcopic indication to complementary diagnostic analysis aiming at choosing
      the most suitable therapy for which colposcopy can show the lesion topography and
      its frequent plurilocalizations.

PMID- 11526692
TI  - Means for STI prevention--how are they applied and how effective are they?
AB  - The present communication concerns factors, the application of which may
      contribute to reduce the transfer rate of sexually transmitted infections (STIs),
      including geomedical aspects. The factors elaborated on are, e.g. maternal health
      care, sexual education early in life, health prevention programmes and sexual
      risk reduction counselling of commercial sex workers, screening activities as
      well as recommendation of preventive strategies based on analyses of monitored
      data from screening studies. Case- and carrier detection stimulated by society-,
      company- and client-initiatives, syndrome-based therapy of STIs, barrier-
      (condom) and hormonal anticonception counselling and the special features of
      HIV/AIDS prevention are also elaborated on. The spread of sexually transmitted
      infections (STIs) in a society and between various geographic areas within and
      between countries is dependent of a large number of factors. The relative
      importance of all such factors have been rather poorly analysed simultaneously in
      one area, particularly with regard to their interactive impact on the
      epidemiology of these infections. Such analyses must, however, be a prerequisite
      for any successful intervention programme attempting to reduce the spread of STIs
      in a society. The present communication will elaborate on a number of factors
      (tab. I), the application of which is believed to be important for reducing the
      transfer rate of STIs, not only between individuals living in one and the same
      community but also between geographically separated community.

PMID- 11526691
TI  - [Bowenoid papulosis: myth or reality?].
AB  - The authors present a review of recent theories about clinical entity of Bowenoid
      Papulosis (P.B.), considering histological and etiopathogenesis aspects. The
      starting point of this review was recent observation of some clinical cases of
      P.B. The HPV is clearly involved in the start and the growth of this pathology.
      However, we have serious doubts regarding the etiopathology role of such virus of
      the pathology and the element of the start of a simil-neoplastic shape because
      the HPV was not found in the clinical shapes that we have examined. The frequent
      spread of the illness might give an answer to the immunology of the patient even
      though there was not significant immunity deficit in the previous cases that we
      have examined. Another remark was noticed by therapy writers. They are wondering
      whether they should practice a therapy called "wait" rather than treatment which
      is sometimes harmful and collateral effects. The last patients who have been
      treated by dtc in the beginning were restricted to local therapies with
      podofilotoxines in rare cases where they were examined after their treatment.

PMID- 11526693
TI  - [Update on medical treatment of condyloma].

PMID- 11526694
TI  - [Ablative therapy of condyloma].

PMID- 11526695
TI  - [Vestibular papillomatosis].
AB  - The aim of the present study is to re-update the clinical significance of
      vestibular papillomatosis. At the beginning of the eighties this condition has
      been related to HPV infection based on histological and/or molecular evidence of
      the virus presence and considered responsible of many cases of pruritus and/or
      vulvodynia. Based upon these findings a lot of clinicians have been treating this
      condition by laser ablation or by topical application of podophyllin or
      trichloroacetic acid. At present the majority of the authors believes that
      vestibular papillomatosis should be considered an anatomical variant of the
      vestibular mucosa not HPV related. Therefore HPV-DNA presence should be
      considered a causal rather than a causal agent. This evidence is important in
      defining the management of vestibular papillomatosis: the papillae are usually
      distinguishable from condylomata acuminata by clinical examination and biopsies
      or HPV testing are not necessary. According to the studies considering vestibular
      papillomatosis a non HPV related condition and on the bases of a series of 252
      women examined, the Authors share the opinion that this clinical entity should be
      considered a normal vestibular findings. As a consequence no ablative treatment
      is usually required even if in presence of symptomatology or HPV molecular
      infection.

PMID- 11526696
TI  - [Typification of HPV in clinical practice].
AB  - OBJECTIVE: To improve the sensitivity of cervical carcinoma screening and to
      determine the optimal management with an ASCUS Pap result we evaluated the
      effectiveness of combining thin layer cytologic slides (ThinPrep) and HPV DNA
      testing. METHODS: A total of 170 women were studied with conventional Pap smears,
      liquid based cytology, HPV testing and colposcopy with eventual histologic
      evaluation. RESULTS: The ThinPrep method yielded 12.5% more high grade lesions
      than did the conventional smears (and more severe diagnoses as compared to the
      conventional smears). HPV prevalence was significantly associated with disease
      status. Of 30 patients with ASCUS, HPV testing detected 100% of high grade
      lesions and 67% of low grade. If colposcopy had been limited to HPV+ women, 47%
      of case would have been spared. CONCLUSIONS: Liquid based cell collection
      improves sensitivity for the detection of disease. For women with ASCUS cytology,
      HPV DNA testing of residual specimen can identify the majority of high risk cases
      using a single sample.

PMID- 11526697
TI  - Screening for Chlamydia trachomatis; the Amsterdam experience.

PMID- 11526698
TI  - [Comparison of methods for monitoring young women with stage I borderline ovarian
      tumor after conservative surgery].

PMID- 11526699
TI  - [Role of intestinal resection in primary cytoreduction of ovarian cancer].
AB  - BACKGROUND: The aim of this study is to define the role of the intestinal removal
      for the therapy of ovarian cancer in advanced stadium. METHODS: We have examined
      247 females with epithelial ovarian cancer in advanced stadium, that had
      intestinal removal. RESULTS: The survival in the females that had a very good
      intestinal removal is greatest than in the females that hadn't a very good
      intestinal removal.

PMID- 11526700
TI  - [Working activity and risk of preterm labor].

PMID- 11526701
TI  - [Cytoreductive surgery in patients with stage IV ovarian carcinoma].
AB  - BACKGROUND: The aim of this study is to evaluate the efficacy of cytoriductive
      surgical in females with ovarian carcinoma in advanced stadium, and to define the
      role of this surgical for the survival of females with hepatic metastases.
      METHODS: This is a retrospective study. 164 females with ovarian cancer in IV
      stadium was examined. 64 females had hepatic metastasis. All patients had
      cytoriductive surgical. RESULTS: The survival in the patients without hepatic
      metastasis was 38 months if the cytoreduction was very good; it was 18.3 months
      if there is residual disease. The survival in the patients with hepatic
      metastasis was 50.1 months if the cytoreduction was very good; it was 27 months
      if there is residual disease. CONCLUSIONS: A very good surgical is very important
      for the survival of patients with ovarian cancer in advanced stadium. This is
      true also in the patients with hepatic metastases.

PMID- 11526702
TI  - [Meigs' syndrome and "Meigs' pseudo-syndrome." Report of 2 cases].
AB  - BACKGROUND: The aim of this study is to investigate similitudis and differences
      between the Meigs' syndrome and Meigs' pseudosyndrom. The Meigs' syndrome is an
      uncommon disease that is characterized by benign ovarian tumor, ascites and
      pleural effusion. The Meigs' pseudosyndrom is a serious disease that is
      characterized by malignant ovarian tumor, ascites, pleural effusion. METHODS: We
      have examined two cases: a case of Meigs' syndrome that is characterized by
      vomit, abdominal pain, ascites, height serum Ca 125 level; a case of Meigs'
      pseudosyndrom that is characterized by ovarian adenocarcinoma that is
      diagnosticated owing to ascites and pleural effusion. CONCLUSIONS: This study
      suggest that the surgical therapy have a very important role for the complete
      remission of the disease in the Meigs' syndrome and for the remission of ascites
      and pleural effusion in the Meigs' pseudosyndrom.

PMID- 11526703
TI  - [Right ovariectomy in patients with borderline stage III/IV endometriosis].

PMID- 11526704
TI  - Immunological variations in women suffering from ovarian cancer. Influence of
      radical surgical treatment.
AB  - BACKGROUND: The immune system includes all the innate or acquired mechanisms,
      that the organism uses for protecting itself from the aggression of external
      pathogens or neoplasia. About the control of the tumor growth, the immune
      mechanisms implicated are quite a lot: the cytotoxicity against the tumor cells
      by cytotoxic T lymphocyte, macrophages, NK cells; simil-NK cells (ADCC). Tumors
      have generally antigenic marked potential, for which numerous antigens have been
      identified, but none of these has revealed a correlated specificity to the
      neoplasia. Only a glycoprotein at elevated molecular weight, the CA125, presents
      an elevated specificity and sensibility. The objective of this study was to
      examine immunological variations in the peripheral blood of patients with ovarian
      carcinoma before and after radical surgical treatment. METHODS: In the Institute
      of Obstetrics and Gynaecology of Second University of Studies of Naples the
      immunological variations in 8 women (mean age: 59.5; range: 49-70 years)
      suffering from ovarian cancer, have been evaluated before and after radical
      surgical treatment (when the stage of the tumor made possible the surgery) and
      compared to 8 normal volunteers of comparable age (control group), in the period
      January 1994-June 1998. The patients were followed in average for two years and
      subjected to a immunological screening with blood drawings effected at the
      hospitalisation and later 1, 6, 12, 18, 24 months from surgical treatment. The
      immune evaluation were effected with: proliferation tests on the monocytes of the
      peripheral blood, evaluation of the production of Interleukin 1 and 2 with the
      leukocyte phenotyping, evaluation of NK cells activity. The patients were
      followed in average for two years. RESULTS: The radical surgery decidedly
      improves the immune response. The ability to produce IL-1 by the lymphocytes of
      the patients object of our study, appeared constantly falling (with reduction of
      about 50%) before the surgery and it meaningfully increases in the post-surgery
      period. The surgery doesn't modify the lymphocytes T helper and T inducer. The
      surgery delays the diminution of the NK cells in a little meaningful way. The
      periodic dosage of the CA125 does not give the same results: in the 60% a
      progressive increase was realised and in the 40% it remained constant.
      CONCLUSIONS: The surgery constantly improved the physical state of the patient,
      determining an increase of the immune response toward the neoplasia, and
      therefore achieving a meaningful increase of survival.

PMID- 11526705
TI  - [Limitations and expectations of Doppler color in the diagnosis of ovarian
      cancer].

PMID- 11526706
TI  - [Small ovarian cysts in postmenopause: assessment of their malignant potential
      with vaginal ultrasonography and tumor marker Ca125 titration].
AB  - BACKGROUND: The aim of this study was to determine the risk of malignancy in
      cystic ovarian tumors < 10 cm in diameter in asymptomatic postmenopausal women.
      METHODS: All cystic ovarian tumors, detected by abdominal and transvaginal
      sonography screening, in asymptomatic postmenopausal women were evaluated with
      respect to size and morphology. Follow-up data were available both on patients
      undergoing surgery and on those who elected to be followed without operative
      intervention. Titration of the tumoral marker Ca125 was carried out, too.
      RESULTS: Unilocular cystic tumors were detected in 32 of 352 postmenopausal
      patients (9%), of 45-65 years of age arrived at the "Centre for diagnosis and
      therapy of menopausal diseases" of the III Divisione di Ginecologia e Ostetricia
      della Seconda Universita degli Studi di Napoli from the 1st January to the 31st
      December 1999. All tumors were < 10 cm in diameter and 98% were < 5 cm in
      diameter; just one tumor was hardly > 5 cm in diameter (5.8), 14 of these cystic
      ovarian tumors (49%) resolved spontaneously within 60 days while 18 (51%)
      persisted. Seven patients with persistent cystic ovarian tumors underwent
      operative tumor removal. Five of these patients had serous cystadenoma and 2
      other women had cystoadenofibroma. Not even one case of ovarian carcinoma was
      found in this group. The remaining 11 patients with unilocular cystic ovarian
      tumors underwent sonography control every 3 months for one year and no one of
      these patients developed ovarian carcinoma. In all these patients the dosage of
      the tumoral marker Ca125 remained under the suspicious threshold of malignant
      ovaric tumor (Ca125 = 35 U/ml). CONCLUSIONS: Unilocular cystic ovarian tumors < 5
      cm in diameter in asymptomatic postmenopausal women were associated with minimal
      risk for ovarian cancer. In contrast, complex ovarian cysts wall abnormalities or
      solid areas are associated with a significant risk for malignancy. These date are
      important in determining therapeutic optimal strategies in these patients.

PMID- 11526707
TI  - Ovarian cancer screening by transvaginal color Doppler ultrasonography.
AB  - BACKGROUND: The need for the early detection of ovarian cancer continues to be
      one of the most important issue in women's health care. The ovarian neoplasia
      characteristically have a scarce symptomatology for which it tries to create a
      sensitive and specific screening test so that the diagnosis could precociously be
      made and, consequently, improve the prognosis with a timely therapy. Our purpose
      was to assess the performance of transvaginal color Doppler ultrasonography in
      ovarian cancer screening. METHODS: In the Institute of Obstetrics and Gynaecology
      of Second University of Studies of Naples, in the period between January 1997 and
      December 1998, 60 women, divided into two groups (the 1st group included 30 women
      in fertile age with standard uterine dimensions, the 2nd group included 30
      menopausal women), were submitted to transvaginal color Doppler ultrasonography.
      Color Doppler ultrasonography was performed with an ESAOTE ANSALDO AU5 HARMONIC
      ultrasound machine provided with a 6.5 MHz real-time sector electronic array
      endovaginal probe with a 5 MHz pulsed Doppler system and equipped with the color
      velocity imaging system for the color blood flow codification. The score used in
      the evaluation of the ovary are us follows: volume of the adnexa (from 1 to 5);
      presence of papillas and septa (from 1 to 5); wall thickness (from 1 to 5). An
      high score (> 12) corresponds to probability of presence of neoplasia. For the
      flow modifications the following parameters were considered: RI (Index of
      resistance); PI (Pulse Index); Vmax (Maximum Speed). CD was considered as
      suspicious when flow was detected and the lowest RI found was < or = 0.45, PI <
      or = 0.58 Vmax < or = 60. RESULTS: Sonographic morphology evaluation and CD were
      suspicious in 11 cases and 9 of these were positive on histopathological analysis
      (true positive = 15%, false positive = 5%). All the women that had
      morphologically normal ovaries observed on ultrasound examination and were not
      suspicious on CD analysis, were also negative on histopathological analysis (true
      negative = 80%). CONCLUSIONS: The color Doppler ultrasonography revealed a
      decidedly valid method of screening of the first level, being non-invasive
      examination, painless, therefore well accepted by the patients, even if in some
      women, especially if in fertile age, the physiological modifications calls for
      repeated investigations and compare its parameters.

PMID- 11526708
TI  - [HPV infection. Clinical features and treatment].
AB  - The aspecific and exiguous symptoms and the lacking information are among the
      reasons of the diffusion of the vulvo-vaginal papillomatosis. We carried out the
      present study between 1995 and 1999 in the outpatient clinic of cervico-vaginal
      pathology of the Second University of Naples. 680 patients (aged between 18 and
      56 years) underwent vulvoscopic and colposcopic examination. The did not show any
      relevant symptoms specific for HPV infection. Among the viral strains, HPV-16 and
      HPV 18 are able to induce a cervical cancer. To eliminate the pathology the
      primary prevention is necessary: it consist of both an adequate information about
      the micro-condilomatosis, the role of the activator agent, the modality of the
      infection, and the annual screening examinations such as pap-test and colposcopy.
      As first line treatment during secondary prevention, we utilize Roferon A, and
      perform diathermocoagulation according with the local diffusion and the degree of
      the disease (mild, moderate, severe). At the end of the therapy with Roferon A we
      observed that the infective focus was eliminated in about 60% of the cases and,
      only for moderate and severe micro-condilomatosis a diathermocoagulation was
      necessary.

PMID- 11526709
TI  - [Gestational HSV in the work setting].
AB  - OBJECTIVE: The purpose of our studies has been that to individualize the in
      partnership factors of risk to infection Herpes Simplex Virus-Type 2 in pregnant
      women and to appraise the role of the job in such context. METHODS: A champion of
      79 pregnant women with infection from HSV-2 has responded to a questionnaire
      regarding the appearance of the infection, her own job and the degree of stress,
      if they used services hygienic public. RESULTS: In this champion of pregnant
      women 63% they are workers. Of these the 85% they introduced signs of a
      reinfection. For the housewives in 67% there was a reinfection. 84% of the
      housewives it uses services hygienic privacies. The infection from HSV has
      appeared in 28.5% of the been born by women with first infection from HSV
      genitalis, and in 12.5% of the been born by women with reinfection from HSV.
      CONCLUSIONS: The women that work are mostly to risk of reinfection, they have
      more evident troubles. This is consequence of a style of life that contemplates a
      state of superior stress and a great tiredness from the same and of the
      appearance of vulvo-vaginal infections sustained by microorganisms transmitted
      through the hygienic services.

PMID- 11526710
TI  - [Use of GnRH analogues in the treatment of virilizing tumors].

PMID- 11526711
TI  - [Second-look in ovarian cancer: laparoscopy or laparotomy?].
AB  - BACKGROUND: The aim of the present study was to compare the laparoscopic second
      look with laparotomic second-look as regards the consistency of diagnosis of
      residual tumoral disease after first step treatment in patients affected by
      ovarian cancer, and to evaluate the feasibility of the laparoscopic second-look.
      METHODS: Twenty-one patients affected by ovarian cancer underwent laparoscopic
      second-look followed by laparotomic second-look. Six months after the first
      surgical intervention all the patients showed no contraindications to
      laparoscopic second-look. All the surgeries were performed with the same
      procedure: after the introduction of the trocars the lysis of adherences was
      carried out, the whole abdominal cavity was explored, 18 abdominal-pelvic sites
      were examined, direct biopsies were performed and samples for the cyto- and
      histological analysis were obtained. RESULTS: Positive predictive value for
      laparoscopy was 100% (6 out of 6 cases), while negative predictive value was 84%
      (2 false negative cases out of 12). The complete abdominal-pelvic examination was
      possible in 95% of cases with laparotomy while in 41% of cases with laparoscopy,
      because of post-operative severe adherences. CONCLUSIONS: Laparoscopic second
      look has a good consistency as regards the diagnosis of residual tumoral disease,
      but its feasibility is lower than laparotomy owing to the presence of severe
      adherences and the high risk of intra- and post-operative compliances.

PMID- 11526712
TI  - [New serum markers in malignant epithelial tumors of the ovary].

PMID- 11526713
TI  - [Second surgery of ovarian carcinoma].

PMID- 11526714
TI  - [Role of intraperitoneal chemotherapy].

PMID- 11526716
TI  - [Chemoresistance in antineoplastic treatment of ovarian tumors].

PMID- 11526715
TI  - [Familial ovarian carcinoma].

PMID- 11526717
TI  - [Recurrence of malignant epithelial tumors of the ovary].

PMID- 11526718
TI  - [Biological factors with prognostic significance in ovarian cancer].

PMID- 11526719
TI  - [Treatment of intestinal and urinary tract obstruction in patients with advanced
      ovarian disease].

PMID- 11526720
TI  - [Role of Ca 125 in pelvic masses. Our experience].
AB  - BACKGROUND: The goal of our study is to plan a screening program for early
      detection of ovarian cancer through clinical examination, pelvic ultrasonography
      and serum Ca 125 dosage. METHODS: Between January 1993 and June 1999, 436
      patients have been submitted to ovarian cancer screening at the Obstetrics and
      Gynecology Institute of the Second University of Naples. All women were in
      postmenopausal period, older than 50 years and didn't show any gynecologic
      disease. RESULTS: Clinical examination selected 41 patients (9.4%) with a pelvic
      mass; pelvic ultrasonography revealed ovarian or uterine mass (only subserous
      myoma) in 87 cases (19.9%). These patients were submitted to Ca 125 serum dosage;
      in three cases Ca 125 was higher than 65 U/ml and in 26 cases its value was
      between 35 and 65 U/ml. The remaining 58 patients showed Ca 125 values lower than
      35 U/ml. Four patients with ovarian cancer have been detected with our screening
      program. CONCLUSIONS: The authors conclude that pelvic ultrasonography and serum
      Ca 125 dosage are useful for the assessment of an early screening program of
      ovarian cancer.

PMID- 11526721
TI  - [Role of echo-guided aspiration of ovarian cysts. Our experience].
AB  - BACKGROUND: Ultrasound-guided puncture is a simple and easy to perform procedure.
      This study was undertaken to verify the role of fine-needle aspiration (FNA)
      followed by cytological examination as a possible alternative to surgery in case
      of cystic pelvic masses. Ovarian cysts are conventionally managed by laparoscopy
      or laparotomy. METHODS: From January 1993 to December 1997, 224 patients with a
      proven cystic pelvic mass underwent surgical intervention and have been
      retrospectively analysed for FNA under sonographic guidance. The sediment
      aspirated was examined by a cytological method and when possible it was also
      correlated to a histological test. RESULTS: Eight patients (34.8%) had been
      submitted to one needle cyst aspiration before surgical intervention and 15
      (65.2%) to more than one aspiration. Patients with an history of only one
      aspiration were submitted to surgical intervention with urgency statistically
      more than the group with an history of more than one aspiration. Anatomo
      pathologic examination showed a significative relevance of serous and
      endometriotic cysts. CONCLUSIONS: We conclude that FNA might be proposed in young
      women with a unilocular ovarian cyst to avoid a surgical procedure. In all
      instances the ultrasonographic appearance of the cyst and the characteristics of
      aspirated fluid are the most important findings.

PMID- 11526722
TI  - [IVF-ET and extrauterine pregnancy. Report of a clinical case].
AB  - A lot of hypothesis have been advanced to explain the aetiology of the ectopic
      pregnancy, even if this one isn't clear yet. We report a case of ectopic
      pregnancy in a patient who was included in an egg-donation program. The patient,
      who was hospitalised urgently, showed symptoms that underlined extra-uterine
      pregnancy which was also confirmed by the ultrasonography. The case was solved by
      salpingectomy during a laparoscopic treatment. Sure, the techniques of the in
      vitro fertilization and embryo transfer are an important risk factor of extra
      uterine pregnancy. Among the qualitative and quantitative aspects, we have to
      consider: the negative influence that the excess of E2 and progesterone has on
      the tubal and endometrial epithelium, modalities of accomplishment of the
      transfer, and at last, the tubal factor infertility. Our conclusion don't support
      the theory which considers E2 and progesterone as the principal cause of ectopic
      pregnancy.

PMID- 11526723
TI  - [Borderline ovarian tumors].

PMID- 11526724
TI  - [Ovarian cysts in adolescence: epidemiologic, clinical and management
      assessment].
AB  - BACKGROUND: To evaluate the frequency of ovarian cyst formation in the
      adolescents and to report on the clinical implications of these cysts. METHODS: A
      prospective analysis of data on 94 girls (aged 10-19) with diagnosed ovarian
      cysts was performed at the Gynecology Department of Aversa and Naples hospitals
      between 1995-2000. Operations were performed because of pains or ultrasound
      suspected features. The patients who were not operated on were kept under
      observation and had ultrasound tests monthly, receiving gestogen to facilitate
      resolution of the cyst and as treatment of menstrual disorders. The site, number,
      size and type of the cysts were examined. RESULTS: The ovarian cysts were
      unilateral, unilocular, and simple, with the size varying between 3 cm and 5 cm
      in 83 cases, more than 5 cm in 8 cases and less than 3 cm in 3 cases. Among 94
      patients 6 (6.4%) were initially qualified for the operation because of the
      strong pains or ultrasound equivocal aspect. Hormonal treatment was given in 74
      cases, whereas in 14 cases only follow up sonography was performed. Cysts
      resolved spontaneously in 2 months on average, or in 1 month after hormonal
      treatment. No malignant tumors were found in the observed group. CONCLUSIONS:
      Clinical observation periodically repeated ultrasound tests seems to be the most
      appropriate procedure employed at adolescent girls with asymptomatic ovarian
      cysts. Hormonal treatment shortened the duration of the cysts somewhat, even if
      in a not significant manner, and thus was useful mainly in the treatment of
      concomitant menstrual disorders.

PMID- 11526725
TI  - [Treatment of ovarian carcinoma with intraperitoneal administration of interferon
      alpha 2b].
AB  - BACKGROUND: Pharmacokinetic studies have confirmed that for many chemotherapeutic
      agents a substantial pharmacological advantage can be achieved using the
      intraperitoneal route. Aim of this study is to evaluate the efficacy of
      intraperitoneal interferon alpha 2b chemotherapy to treat ovarian cancer.
      METHODS: Forty-four patients affected by ovarian cancer have been submitted to
      intraperitoneal interferon alpha 2b chemotherapy from October 1989 to May 1996 at
      the Gynecology and Obstetric Institute of the Second University of Naples.
      Intraperitoneal route has been obtained through a catheter in left iliac fossa.
      Drugs have been solved in 2000 ml of physiologic solution to obtain a better
      distribution into the peritoneal fluid. RESULTS: Three patients of 15 not-pre
      medicated and 16 of 24 pre-medicated have obtained complete anatomo-pathological
      resolution. No compliances have been checked about catheter. Only two patients
      have stopped the therapy for asthenia; all the others have well tolerated
      interferon. CONCLUSIONS: Our study shows the very low toxicity of interferon
      associated to a good tolerance of the intraperitoneal catheter and therefore we
      retain that intraperitoneal chemotherapy with interferon alpha 2b improves the
      prognosis of patients with minimal ovarian cancer after systemical chemotherapy.

PMID- 11526726
TI  - [Review of the literature on BRCA 1 and BRCA 2].

PMID- 11526727
TI  - Contraception with the latest estroprogestagens in women suffering from systemic
      lupus erythematosus.
AB  - BACKGROUND: This study was performed to evaluate, in women suffering from
      Systemic Lupus Erythematosus (SLE), the relationship between the assumption of
      oral contraceptives and the evolution of the disease. METHODS: In the Institute
      of Obstetrics and Gynaecology in collaboration with the Institute of
      Dermosyphilopathical Clinic of Second University of Studies of Naples, 20 women
      in fertile age suffering from SLE with specific cutaneous manifestations were
      studied for the year 1999. All the patients requested to take, at contraceptive
      purpose, low-dosage estroprogestagens. The contraceptives we prescribed have, as
      active substance, the gestodene at the dose of 0.075 mg and the etinilestrdiol at
      the dose of 0.02 mg per day. Patients' group in object was compared for a year
      with a similar control group of women suffering from SLE not subjected to any
      pharmacological therapy. RESULTS: Only 5 patients out 20 have had to suspend
      therapy after 4 or 5 months, because a relapse of the illness was experienced
      while the others 15 patients did not lament a relapse of the illness. In the
      control group a more or less similar percentage of patients, during the months of
      the observation, spontaneously had episodes of relapse of the illness.
      CONCLUSIONS: The results of our brief study have shown that the administration of
      hormonal contraceptives in reality doesn't constantly produce immediate and
      remarkable exacerbations of the illness in women suffering from SLE. In our
      opinion the contraception with the latest estroprogestagens can comfortably be
      effected under strict medical control, probably because the medicines at low
      dosage are quickly metabolized and in the majority of the cases they don't have
      capacity to influence the course of such chronic connectivitis.

PMID- 11526728
TI  - [Risk of chromosomal pathology in fetus with abnormal umbilical artery
      flowmetry].
AB  - BACKGROUND: Goal of this study is to consider the incidence of chromosomal
      abnormalities in fetuses by velocimetry abnormalities. METHODS: The author select
      64 pregnancies by velocimetry abnormalities of umbilical artery diastolic flow
      (ARED: Absent or Reverse end Diastolic Flow). RESULTS: The fetal cariotype from
      amniociti or from umbilical blood at delivery moment is resulted abnormal in 5
      cases. Fetal-maternal risk factors of chromosomopaties are: malformations; fetal
      growth retardation; maternal age > or = 35. CONCLUSIONS: Other studies and other
      results are necessary for this discussion.

PMID- 11526729
TI  - [Usefulness of ultrasonography of the cervical canal in the screening of pregnant
      women at risk of premature labor].
AB  - BACKGROUND: Goal of the study is to evaluate the utility of cervical sonography
      in the second quarter as screening of pregnancies with risk of preterm labor.
      METHODS: A.A. evaluate, by transvaginal sonography (TVS) of the uterine cervix,
      75 pregnancies with history of preterm labor and 25 with risk of preterm labor
      between XXIV and XXXIII week of pregnancy. The uterine cervix length < 40 mm and
      width > 5 mm, funneling were pathological and predictive factors of preterm
      labor. RESULTS: Eighty-five percent of pregnancies that have, at sonography TVG,
      abnormal values of length and width of uterine cervix, delivered before XXXVI
      week. CONCLUSIONS: These results confirm the importance of the high frequency
      ultrasonography transvaginal, TVS, for its predictive value and for treatment in
      pregnancies with risk of preterm labor.

PMID- 11526730
TI  - [Psychological features of ovarian cancer in the elderly].

PMID- 11526731
TI  - [Study on a sample of working pregnant women, with previous pregnancy at risk,
      with preventive polyunsaturated fatty acid supplementation].

PMID- 11526733
TI  - Medical jargon and legalese.

PMID- 11526732
TI  - [Borderline ovarian tumors. Retrospective analysis of 20 cases].
AB  - BACKGROUND: To evaluate the clinical features, the surgical management and
      outcome of 20 patients with stage-I borderline ovarian tumors. METHODS: Twenty
      cases of FIGO stage-I ovarian tumors, aged from 31 to 58 years (mean 37 years)
      have been reviewed. All informations of clinical stage, surgical intervention and
      prognosis were achieved by reviewing hospital records. Minimal requirements for
      conservative management were adequate staging and complete information about the
      therapeutic options. Factors important in the choice of the treatment were, age,
      wish to preserve fertility, histologic type and grade, and the stage of the
      tumour. RESULTS: Eleven of the 20 patients (55%) were at stage IA, 6 cases (30%)
      were at stage IB, 3 cases (15%) were at stage IC. Thirteen (65%) were with
      mucinous cystadenoma of borderline malignancy, 7 cases (35%) were of serous type.
      Thirteen patients underwent total abdominal hysterectomy and bilateral salpingo
      oophorectomy (TAH and BSO). Seven patients were treated with unilateral
      oophorectomy or unilateral salpingo-oophorectomy (USO). One patient underwent
      enucleation of ovarian tumor and biopsy of contralateral ovary. Any patient were
      treated with chemotherapy after operation. With a median follow up of two years,
      we observed no recurrence of carcinoma in women treated conservatively or in
      those treated more radically. CONCLUSIONS: Conservative surgery remains a
      therapeutic option in selected patients with borderline ovarian tumors. Prolonged
      intensive follow-up is required for women treated conservatively for borderline
      malignant ovarian tumours.

PMID- 11526734
TI  - Liquid nutritional supplements.

PMID- 11526735
TI  - JCAHO update. Human resources.

PMID- 11526736
TI  - Assembly and intracellular trafficking of GABAA receptors.

PMID- 11526737
TI  - Molecular modeling of ligand-gated ion channels: progress and challenges.
AB  - There has been rapid progress in molecular modeling of LGICs in recent years. The
      convergence of improved software for molecular mechanics/dynamics, techniques of
      chimeric substitution and site-directed mutations, and the first X-ray structures
      of transmembrane ion channels will make it possible to build reasonable models of
      neuronal ion channels well in advance of publication of their crystal structures.
      These models will not only serve as guides for future site-directed mutagenesis,
      but they will also be a starting point for understanding the dynamics of ion
      channel gating.

PMID- 11526738
TI  - Alzheimer's disease: its diagnosis and pathogenesis.
AB  - A hypothesis has been presented that links many of the identified and putative
      risk factors for AD and suggests a mechanism for their action. Crawford (1996,
      1998) proposes an association between AD and cerebral blood flow (CBF) by citing
      evidence that many of the factors that are linked with an increased risk of AD
      also decrease CBF (e.g., old age, depression, underactivity, head trauma).
      Similarly, it is suggested factors that increase CBF are associated with a
      decreased risk of AD (e.g., education, exercise, smoking, NSAIDs). Although the
      authors acknowledge that reduced CBF is not sufficient to cause AD, the reported
      positive and negative associations provide tantalizing evidence for a common mode
      of action for many of the equivocal risk factors reported to date. This
      hypothesis is also consistent with other data that links microvascular damage and
      impaired blood flow (de la Torre, 1997, 2000) and low education with increased
      cerebrovascular disease (Del Ser et al., 1999). Gaining a better understanding of
      the interaction between AD and vascular disease is of great importance. Not only
      will it provide insights into the pathogenesis of AD, but it may also provide us
      with a rare opportunity for the treatment and possible prevention of AD. A great
      many risk factors for vascular disease have been identified and intervention
      programs have successfully reduced the incidence of heart disease and stroke. The
      potential exists to provide the same level of success with AD.

PMID- 11526739
TI  - DNA arrays and functional genomics in neurobiology.

PMID- 11526740
TI  - Subcellular localization and regulation of GABAA receptors and associated
      proteins.

PMID- 11526741
TI  - D1 dopamine receptors.

PMID- 11526742
TI  - [Results of 1043 prenatal cytogenetic studies: retrospective study in the context
      of applicability of interphase FISH in prenatal diagnosis]].
AB  - OBJECTIVES: The risk of aneuploidy in a fetus is the main reason for referral in
      approximately 80% of prenatal studies. Recently, a new method for rapid detection
      of the most frequent aneuploidies affecting chromosomes 13, 18, 21, X and Y has
      been developed. Fluorescence in situ hybridisation (FISH) on uncultured fetal
      cells with probes specific for these chromosomes has been described which enables
      diagnosing aneuploidies within 24 to 48 hours. The purpose of the study was
      evaluation of clinical utility of this new method in prenatal diagnostics.
      MATERIALS AND METHODS: Retrospective analysis of the results of 1043 prenatal
      cytogenetic studies performed with conventional banding methods was done. Number
      and type of chromosomal abnormalities found in different categories of
      indications with special emphasis on aberrations undetectable by FISH were
      analysed. RESULTS: Chromosomal aberrations were found in 4.7% studies. The
      frequency of aneuploidies was 1.8% accounting for 35.8% of all diagnosed
      chromosomal abnormalities. In the group of 854 studies performed for elevated
      risk of aneuploidy it accounted for 60.7% (17/28) abnormalities. All other
      aberrations could not be detected by FISH with probes for most frequent
      aneuploidies. Among them, there were 6 unbalanced: del (8) and pseudic (15) with
      known abnormal phenotype and 4 marker chromosomes with unknown clinical
      consequences. Three other abnormalities were balanced but familial origin of them
      was documented. CONCLUSIONS: A karyotype using classical banding methods should
      be performed whatever the indication of prenatal study is. It is the only fully
      informative method able to detect all chromosomal abnormalities. Interphase FISH
      assay must be considered as a complementary procedure to fetal karyotype analysis
      as it is designed only for aneuploidy identification. However it may be a very
      useful method for rapid diagnosis in specific clinical conditions especially in
      the cases of high risk of aneuploidy.

PMID- 11526743
TI  - [Prenatal and neonatal diagnosis of osteogenesis imperfecta in obstetrical
      practice].
AB  - Osteogenesis imperfecta (OI types I, II, III, IV) is a heterogeneous group of
      genetically disorders of connective tissue. Quantitative or qualitative
      abnormalities of type I collagen form pathogenetical basis of the disease. They
      are caused by mutations in genes encoding collagen proteins or enzymes involved
      in collagen biosynthesis. The clinical features of each type usually correspond
      to the type of mutation. Typical manifestations are fragile bones with multiple
      bone fractures and bone deformities. Currently applied diagnosis in utero of OI
      II and sometimes OI III may be performed. Diagnosis of other OI phenotypes cannot
      be made until after birth. We present three cases of OI II (four children)
      diagnosed, in utero, by ultrasound examination. The analysis in work include: 1.
      the prenatal sonographic features of OI type II 2. the biochemical properties of
      collagen in the above cases 3. genetic counselling of the families affected by
      OI.

PMID- 11526744
TI  - [Endometrial carcinoma in patients with family history of neoplasms].
AB  - OBJECTIVES: The aim of the study was multifactorial clinical analysis of patients
      with neoplasmatic family history operated because of endometrial carcinoma in 2nd
      Dept. of Obstetrics and Gynecology Medical University of Gdansk between 1983
      1997. MATERIAL AND METHODS: The group of 117 women who answered inquiry forms was
      analysed. The other data was obtained from case histories. The subgroup of
      patients with neoplasmatic family history was selected. RESULTS: The subgroup of
      patients with neoplasmatic family history was 41.9% of all treated women (49
      women). The median age was 58.8; most of them were para- and postmenopausal
      women. In the group of patients with adenocarcinoma of endometrium the
      neoplasmatic family history was obtained twice more often then in group with
      adenosquamous carcinoma. The neoplasmatic disease was found in different members
      of family (parents, sisters, brothers, grandparents, uncles, aunties and other).
      In 1/3 cases a neoplasmatic disease was found in few members of the family.
      CONCLUSION: Women with neoplasmatic family history have to be controlled more
      strictly because of "coexisted" genetic, internal and economic factors.

PMID- 11526745
TI  - [Analysis of pulmonary venous blood flow in growth retarded fetuses above 30
      weeks of gestation].
AB  - Abnormal spectra of blood flow are observed in many fetal vessels in pregnancy
      complicated by intrauterine growth restriction. Redistribution of blood flow to
      the most important organs causes a diminished perfusion of the others. The
      disturbances of lung perfusion in utero are related to abnormal growth and
      development of the fetal lung. The aim of this study was to describe blood flow
      velocity waveforms in fetal pulmonary veins in normally grown and growth
      restricted fetuses above 30 weeks of gestation. Doppler studies were performed in
      53 normally grown and 39 growth restricted fetuses. The subjects of analysis
      were: peak systolic (VS), peak diastolic (VD), end-diastolic (VA), and
      pulsatility index for veins (PIV). Analysis was performed for two gestational
      intervals: 31-36, 37-41 wks. The pulmonary venous flow in growth retarded fetuses
      demonstrates the similar pattern to that observed in normally grown fetuses above
      30 weeks of gestation. There were no statistically significant differences
      between normally grown and growth restricted fetuses in all analyzed indices in
      both gestational intervals.

PMID- 11526746
TI  - [Proteolytic activity of placenta with EPH-gestosis determined by casein and
      azocasein].
AB  - Total proteolytic activity, activity of cathepsin B, activity of cysteine
      cathepsins and contents of protein degradation products were determined in
      placentas of pregnancies complicated with mild, moderate and severe EPH-gestosis
      and in placentas from normal pregnancies. The highest activity of all the
      determined proteases was observed in placentas of pregnancies complicated with
      severe EPH-gestosis. The placentas of pregnancies complicated with severe EPH
      gestosis also include the highest amounts of aminoacids and low-molecular
      peptides.

PMID- 11526747
TI  - [The evaluation of complications caused by insertion of Veres needle and trocars
      placement based on analysis of 4211 laparoscopic operations].
AB  - The retrospective analysis of 4211 laparoscopic operations was performed. The
      complications caused by insertion of Veres needle and trocars placement were
      found in 66 cases (1.6%). There were: retropneumoperitoneum--in 33 cases
      (8@1000), vascular injuries--22 cases (5@1000), injuries of the gastrointestinal
      organs--9 cases (2@1000). In 2 cases (0.4@1000) perforation of the wall of
      urinary bladder occurred. The accurate preparation of patients to laparoscopy,
      knowledge of management with complications, ability to laying sutures through all
      of abdominal layers, using of Foley's catheter for haemostasis enabled to cure
      both the main disease and complications.

PMID- 11526748
TI  - [Application of pcr in paternity determination in pregnancy preceded by rape].
AB  - Authors present a case of PCR (Polymerase Chain Reaction) technique application
      for the paternity determination in pregnancy preceded by the rape. Diagnostic
      material was obtained in the 10th week of pregnancy by the use of transabdominal
      Chorionic Villous Sampling under the echo-guidance and its DNA feature was
      compared against the DNA material obtained from the vagina after the rape and the
      material from mother and her husband. The PCR technique revealed in chorionic
      villi the presence of allele that were present in material deriving from mother
      and her husband as well as no even single allele from the material of violator.
      Exclusion of violator as a father of the foetus effected in decision of
      continuing the pregnancy.

PMID- 11526749
TI  - [Regular menstrual bleeding in a woman after hysterectomy].
AB  - The authors present a rare case of 39 years old woman, who had regular monthly
      bleedings mimicking menstruation during the two years after abdominal
      hysterectomy (without the adnexa). The woman was operated on in 1997 because of
      large uterine myoma and presented no other pathology in the abdominal cavity. She
      also suffered from autoimmunological anemia and chorea, which decreased her life
      activity and resulted in lack of gynecological care after the operation. The
      patient misunderstood the effect of surgery and mistook bleedings for signs of
      normal hormonal function. Deep external endometriosis of vaginal cuff and
      surrounding tissues was the cause of 'menstruation'. All this tissues were
      surgically removed. An immunological mechanism which plays role in endometriosis,
      chorea and anemia, was discussed.

PMID- 11526750
TI  - [Pruritic urticaria-related papules and plaques of pregnancy: a case report].
AB  - Rarely met pruritic urticarial papules and plaques of pregnancy usually are
      connected with multiply pregnancy. Disease begins in the third trimester of
      pregnancy, doesn't react on treating and disappear after delivery. In the
      reported case massive skin changes disappeared in a few days after caesarean
      section.

PMID- 11526751
TI  - [Lung hypoplasia and the application of Doppler ultrasonography in the assessment
      of fetal pulmonary circulation].
AB  - The paper presents a review of literature concerning the use of Doppler technique
      in the evaluation of pulmonary blood flow. Especially, it is important to monitor
      the development of lung in suspicion of lung hypoplasia that closely correlates
      with abnormal development of pulmonary vessels. In the literature there are
      single reports pointing on its usefulness in the detection of lethal lung
      hypoplasia. It has been suggested that this technique may provide valuable
      information of the development of vascular bed in lung. Recent data concerning
      Doppler blood flow velocimetry in hypoplastic lung stimulate to further studies
      suggesting their significant value in the diagnosis and distinguishing the lethal
      form of pulmonary hypoplasia.

PMID- 11526752
TI  - [Primary hypertension, positive family history and pregnancy].
AB  - The greatest belief that the group of patients with primary hypertension is
      heterogeneous and the progress which took place in the last few years in the
      research study concerning primary hypertension induced to recapitulation of the
      given data to asses the influence of the primary hypertension on the pregnant
      woman and the fetus. The study presented with clinical data claims that 50% of
      women with mild and moderate primary hypertension showed spontaneous reduction of
      blood pressure levels in the first months of pregnancy. The results should be
      taken under consideration when treating the hypertension. Simultaneously, at
      present the medicine does not posses the ability to indicate the type of
      hypertension which manifests itself in the second half of pregnancy, it is being
      proposed to monitor the evaluation of the renin-angiotensin-aldosterone system
      during pregnancy, as being helpful to the physician. All the study concerning the
      activity of the RAA system during pregnancy with the pregnancy induced
      hypertension showed remarkably lower growth levels with the gestational age
      unlike the pregnancy with the primary hypertension. The mild as well as moderate
      primary hypertension does not implicate any danger to the woman nor the fetus.
      But the simultaneous incidence of the pregnancy induced hypertension deteriorates
      the prognosis for both the woman and the fetus. The most sensitive prognostic
      factor for the pregnant woman with primary hypertension is the evaluation of the
      blood pressure levels in the first half of pregnancy. The study also covers the
      importance of the arterial hypertension family history among both healthy and
      those with primary hypertension pregnant women.

PMID- 11526753
TI  - [Risk of skeletal system damage caused by heparin administration in pregnant
      women: review of literature].
AB  - Long-term administration of heparin can lead to development of osteoporosis. The
      review of clinical studies of the effects of standard heparin and low molecular
      weight heparins on the skeletal system of pregnant women is presented.

PMID- 11526754
TI  - [Surgical treatment of intrapelvic endometriosis].
AB  - The paper is a review of the surgical treatment of women intrapelvic
      endometriosis with attention to the extent of the intervention, the selection of
      appropriate procedure and employment different techniques and innovations in
      surgical therapy. Principles of the management of deep infiltrating
      endometriosis, methods of relieve the pelvic pain and the prevention of
      postoperative adhesion are also discussed.

PMID- 11526755
TI  - [Ovarian cancer and endometriosis].
AB  - Endometriosis is a relatively common condition found in up to 29% of women
      undergoing laparotomies. The authors suggest that endometriosis could have
      undergone malignant change. They propose the criteria used to establish that a
      malignant tumor has develop in endometriosis: clear evidence of endometriosis
      should be found close to the tumor, the histopathological appearance should be
      such that origin of the tumor from endometriosis is plausible, no other primary
      site should be found. The authors consider that atypical endometriosis possesses
      a precancerous potential or is most frequently associated with endometrioid and
      clear cell carcinomas.

PMID- 11526756
TI  - [Application of IVF in women with endometriosis].
AB  - Application of IVF at women with endometriosis after pharmacological and surgical
      therapy hold out hopes to possession of child. Endometriosis occurs three times
      more often in the patients with primary sterility than in patients with secondary
      sterility. The presence of a small endometriosis does not reduce the success of
      the IVF therapy. The women with endometriosis who undergo IVF treatment have
      similar prospect in compensate with women with tubal sterility. IVF improve
      fertility in women with mild or minimal endometriosis. But at women after IVF the
      presence of endometriomas is associated with increased rates of early pregnancy
      losses. Women with endometriosis marking often antinuclear antibodies and
      antiphospholipid antibodies than women without endometriosis. To evaluate the 15%
      of infertile women have endometriosis.

PMID- 11526757
TI  - [The results of GnRH analog treatment of endometriosis].
AB  - Our study consisted of 146 patients with endometriosis diagnosed during
      laparoscopy. The age of those women varied from 19 to 43. Pathological changes
      were classified according to Revised American Fertility Society scale. Numeric
      scale was also used to evaluate clinical symptoms characteristic to this disease.
      During the initial laparoscopy biopsies were taken, endometrial implants were
      coagulated, pelvic adhesions deliberated and endometriomas were enucleated or
      their wall cut out and coagulated. When endometriosis was histopathologically
      confirmed the hormonal treatment was undertaken during a period of time from 3 to
      6 months depending on the severity of the disease. The patients were treated with
      3.6 mg gosereline and 3.75 mg triptorelin monthly or with 400 mcg of naphareline
      daily. The hormonal therapy was monitored by the concentration of estradiol in
      blood serum. After full cycle of GnRH analogues treatment laparoscopy was
      repeated. The mean of The Symptom Severity Scores decreased from 7.1 to 2.1 after
      the treatment which is a 70% decrease. In the group of women with pain complains
      96% of patients noticed improvement, in the group suffering from infertility
      there were 26.3% of patients who got pregnant. GnRH analogues were good tolerated
      by patients during the treatment.

PMID- 11526758
TI  - [Nafarelin acetate (Synarel) and thermocoagulation in the treatment of
      endometriosis].
AB  - We evaluated the results of united treatment (thermocoagulation and nafarelin
      acetate) of the node type of endometriosis) among women with pain syndrome in
      pelvis minoris. During the treatment we observed withdrawal of pain in lower
      abdomen among 60% of patients and assuagement in remaining cases. During the
      treatment by Synarel the menses were absent together with complaints connected
      with menstruation. The efficacy of the drug together with surgical intervention
      was many times higher then that of thermocoagulation alone.

PMID- 11526759
TI  - [Decapeptyl (triptorelin) in the treatment of endometriosis genitalis externa].
AB  - The study involved 69 patients in whom endometriosis was diagnosed. The patients
      were divided into three groups randomly. In each of the groups, a different
      method of treatment was applied. In group A thermocoagulation was used, in group
      B triptorelin was used and in group C the above monitored methods of treatment
      were applied. Combined therapy involving the use of both thermocoagulation and
      triptorelin seen to be the most effective.

PMID- 11526760
TI  - [The evaluation of the effect of combined treatment (laparoscopic ante-fixation
      of the uterus and Danazol-therapy) in patients with endometriosis and
      retroflexion of the uterus].
AB  - 14 patients suffered from endometriosis and retroflected uterus were presented.
      They were treated with laparoscopic ante-fixation of the uterus and Danazol
      therapy. Combined treatment was successful, the pain had ceased.

PMID- 11526761
TI  - [Treatment of endometriosis with dienogest: preliminary report].
AB  - AIM OF THE STUDY: Influence of two hormonal therapies (GnRH agonist--leuprolein
      acetate and a new progestin--dienogest) on symptoms of endometriosis in patients
      with different clinical grade of disease. MATERIAL AND METHODS: 34 women with
      endometriosis confirmed by laparoscopy and histology were included into the
      study. Patients were randomized and divided into two therapeutic groups. One
      group was treated with dienogest and the second with leuprolein acetate during 6
      month of study. The intensification of pain was assessed with Visual Analog Scale
      (VAS) and pelvic symptoms scale before, during (3 month) and after therapy.
      Dyspareunia was assessed with pelvic symptoms scale before, during (3 month) and
      after therapy. Frequency of adverse effects was assessed in 1, 3 and 6 month of
      therapy. Emotional state, bone density and basic serum parameters were assessed
      before and after therapy. RESULTS AND CONCLUSIONS: Dienogest as well as
      leuprolein acetate decreased pelvic pain and dyspareunia. There were no
      differences between these influences. Dienogest did not reveal androgenic
      activity (did not reveal activity nor intense seborrheic lesions, nor hirsutism,
      nor voice tone). Dienogest did not reveal hot flashes. Bleeding (caused by
      dienogest therapy) did not influence hematologic indices nor affected the
      patients' decision on preterm end of treatment.

PMID- 11526762
TI  - [Endometriosis of the lungs: analysis of diagnosis and therapy].
AB  - A casuistic case has been presented with endometriosis of the lung in an 18-year
      old girl. Several diagnostic difficulties including haemoptysis accompanying
      changes in the hings and chest, suggesting a npl process. The final diagnosis has
      been made after the second thoracotomy and was confirmed by the histopathological
      examination of the lungs and pleurae. Because of the patient's age the a-GnRH
      therapy was not taken and the treatment with new progestin (dienogest) was
      administered. The 4-months therapy have appeared to be fully positive without any
      side effects.

PMID- 11526763
TI  - [Pneumothorax during menstruation: a case report].
AB  - Endometriosis is a condition where endometrial glands lie outside the uterine
      cavity. The underlying pathophysiological mechanism remain unclear. Pelvic
      localizations are common but thoracic are possible. Catamenial pneumothorax is a
      clinical variant of spontaneous pneumothorax. The 39 years old women with
      catamenial pneumothorax is reported. Patient suffered from endometriosis.
      Diagnosis was established on clinical grounds. After laparoscopy the danazol
      treatment was started.

PMID- 11526764
TI  - [Adnexectomy as therapeutic method of non-operative case of endometriosis: a case
      report].
AB  - Perianal endometriosis is an infrequent form of extragenital endometriosis. A
      case of endometriosis in an episiotomy scar with involvement of the external anal
      sphincter is presented. The question of treatment is discussed. Adnexectomy is
      suggested when wide involvement of the external anal sphincter is diagnosed.

PMID- 11526766
TI  - [Adenomyosis. Diagnostic technique and treatment].
AB  - STUDY OBJECTIVE: A retrospective analysis of ultrasound diagnosis of adenomyosis.
      DESIGN: Evaluation of 149 cases of hysterectomy excluding cases of ovarian and/or
      cervical carcinoma. MATERIAL AND METHODS: Pre-operative ultrasound results were
      analyzed in 149 cases of hysterectomy. Uterine morphometry and myometrial
      echogenicity were assessed. RESULTS: Adenomyosis was diagnosed in 19 cases of
      hysterectomy. Preoperative ultrasound demonstrated a sensitivity of 88.8% and
      specificity of 94.6%. No correlations of adenomyosis with uterine leiomyomas or
      endometrial pathology were found. CONCLUSION: Adenomyosis was found in 12% of non
      oncological cases of hysterectomy. Preoperative ultrasound established the
      diagnosis of adenomyosis.

PMID- 11526765
TI  - [Endometriosis in surgical scars after cesarean section comparison of the
      operative methods].
AB  - The investigation group comprised 33 women who, between 1983-2000, passed an
      operation of removal of endometrial tumors in site of abdominal scars after
      cesarean section. Among 15 patient routine procedures are performed while among
      18 patients the endometrial tumors were enucleated using coagulation. Separation
      of endometrial tumors which usually does not have a distinct outlines and often
      infiltrates the surrounding tissues by using coagulation, leads to smaller
      bleeding and enable the complete excision of the tumor.

PMID- 11526767
TI  - [Initial analysis of chocolate cysts operated on by laparoscopy].
AB  - 53 women with an ovarian chocolate cyst were operated in a laparoscopy. A
      histopathological examination showed 60.4% of endometriomas and 39.6% of
      hemorrhagic lutein cysts. The average age of patients with endometriomas was 33.9
      while of the ones with hemorrhagic lutein cysts was 28.6. The operated patients,
      who were under 35 years old, could be divided into halves, one half of them had
      endometriomas while the other half had hemorrhagic lutein cysts. However,
      endometriomas appeared significantly more often in the group of operated patients
      who were older than 35 years old.

PMID- 11526768
TI  - [The course of interstitial part of ovary duct in relation to prevalence of
      pelvic endometriosis].
AB  - The aim of the study was to assess the anatomical course of interstitial part of
      fallopian tubes in relation to pelvic endometriosis. The study comprised of 154
      dissected oviducts. In 114 (74.02%) cases the course was tortuous, 21 (13.64%)
      curved and in 19 (12.34%) straight. Pelvic endometriosis was confirmed by
      histopathological examination of 12 women. In all of these cases the course of
      interstitial part of oviducts was straight or curved at least on one side. Any
      woman who had bilaterally tortuous course of the interstitial part of the
      oviducts had no endometriosis.

PMID- 11526769
TI  - [Extraperitoneal inguinal endometriosis].
AB  - The case report of the very rare, extraperitoneal endometriosis in the inguinal
      localisation in 40-year-old woman. Clinical diagnosis was confirmed by
      histological examination of the removed endometriotic focus. The main patient's
      complain was the pain in the groin during menses often accompanied with the
      feeling of dumbness of the ipsilateral leg. During menses the palpable tumor
      enlarged and was painful. The surgical excision of the tumor with broad margins
      is the best method of treatment. In differential diagnosis one should consider
      entrapped inguinal hernia as well as displaced ovary.

PMID- 11526770
TI  - [Adolescent endometriosis].
AB  - DESIGN: The aim of our study was estimation of frequency of occurrence
      endometriosis at girls operated from different indications, research of
      predisposing factors and estimation of selected biophysical parameters. MATERIAL
      AND METHODS: Material determined 14 of patients in 13 to 21 years old of life
      operated on account of endometriosis of sexual organs in our Clinic in years 1996
      1999. We study the frequency of occurrence of illness, analysis of perceptible
      clinical reasons, clinical stage of disease using ASF classification. It was
      analysed according to gynaecological age of girls, periodical complaints,
      cystical changes in ultrasound investigation. In serum of blood the level of
      CA125 was analysed with ready sets of firm Abbott. Congenital malformations were
      classed according to Buttram classification. CONCLUSIONS: On base obtained of
      results one ascertained, that protracted pain in pelvis not responding to
      analgesic and antiphlogistic treatment is indication to complex diagnostics with
      regard of laparoscopy making possible diagnosis of endometriosis. One ascertained
      also, that sensibilizing of doctors on predisposing factors to formations of
      endometriosis (congenital malformations, intrauterine device) can contribute to
      preventive activities.

PMID- 11526771
TI  - [Two years experience of laparoscopic management of the deep posterior vaginal
      endometriosis].
AB  - Our three year experiences of laparoscopic operations recto-vaginal endometriosis
      is presented here. We treated 15 patients. The main symptom was severe
      dyspaurenia. Laparoscopic (n = 14) and laparotomic (n = 1) excision of
      endometriotic nodules resulted in considerable pain relief. The surgical
      techniques was excision with scissors and bipolar coagulation. In all the
      procedures the anterior rectum was freed to the loose areolar tissue of the recto
      vaginal septum, prior to excising deep fibrotic endometriosis. Operation time was
      average 135 minutes and intraoperative blood loss was minimal. Postoperative
      hospital stay was average 4.8 days. Fourteen patients were free from the
      preoperative symptoms at six month follow-up. Laparoscopic surgery for deep recto
      vaginal endometriosis is an effective treatment and offers significant symptom
      relief.

PMID- 11526772
TI  - [Comparison of the efficacy of treatment by two laparoscopic techniques combined
      with medical treatment of endometriosis stage three and four].
AB  - 20 patients were treated for endometriosis with combined treatment, we have
      divided prospectively our patients on the 2 groups. One group was operated by
      laparoscopic marsupialisation of endometrial cyst and coagulation. The second
      group was operated by stripping of lining. Second-look laparoscopy was performed
      after six month medical treatment. Two techniques laparoscopic was very efficacy
      (decrease of AFS score). The difference between them wasn't significant.

PMID- 11526773
TI  - [Ultrasonographic picture of endometrial tumors of ovaries].
AB  - The retrospective analysis was made of 599 patients with ovarian tumours who
      underwent operation in Central Hospital of Ministry of Internal Affairs at
      Department of Obstetrics and Gynaecology during 1991-1999. All the patients were
      examined before operation by transabdominal and/or transvaginal ultrasonic probe.
      A total of 114 endometriotic masses were diagnosed (20 patients had bilateral
      masses). We noted 83 (72.8%) unilocular cysts, 23 (20.1%) multilocular cysts and
      7 (6.2%) partially solid tumours. The so-called "typically" monolocular round
      shaped, smooth-walled endometriotic cyst with diffuse low-level internal echoes
      was only found in 48%.

PMID- 11526774
TI  - [Diagnostic value of transvaginal ultrasound in the detection of ovarian
      endometriosis].
AB  - The aim of the study was to estimate of efficiency of endovaginal ultrasonography
      in diagnosis of ovarian endometriosis. The study was performed in 59 women with
      ovarian tumors. Ultrasound examinations were performed with Aloka 2000 using 5.0
      MHz transducers. The endovaginal ultrasonography is very useful in diagnosis of
      ovarian endometriosis, showing sensitivity--90%, specificity--68%, positive
      predictive value--75%, negative predictive value--86%. Ultrasound examination is
      an important tool in noninvasive diagnostic procedure of adnexal pathology.

PMID- 11526775
TI  - [Endometriosis of the appendix vermiformis].
AB  - 11 cases of the endometriosis of the appendix vermiformis were analyzed among
      women in age between 19-57 years. We observed that endometriosis of appendix were
      accompanied by advanced stages of the ovarian or peritoneum endometriosis in 9
      cases. Diagnosis of endometriosis of the appendix is almost impossible before
      operation because it often could be covered by other genital organs diseases such
      like: uterine fibromas, ectopic pregnancy, PID. The clinical symptoms of
      appendicitis observed before an operation seldom find confirmation in results of
      additional laboratory tests.

PMID- 11526776
TI  - [Endometriosis of the abdominal wall: diagnosis and treatment techniques].
AB  - An analysis of abdominal wall endometrioma management was performed. History of
      cesarean section and/or uterine surgery and ultrasound are important in the
      diagnosis. Danazol test may confirm the diagnosis as well as reduce tumor size
      before operation. HF Electrosurgery, including spray coagulation technique are
      recommended in all cases. Hormonal therapy, including Danazol,
      Medroxyprogesterone or Lynestrenol gives poor effects in cases of endometrioma.

PMID- 11526777
TI  - [Ovarian endometriomas during pregnancy].
AB  - OBJECTIVES: Endometriomas are rare in pregnancy. May be difficult to diagnose and
      may cause significant complications at any stage during gestation. MATERIALS AND
      METHODS: The author presents 2 cases of ovarian endometriomas diagnosed and
      treated surgically in 14 and 18 weeks of pregnancy. In the first case laparoscopy
      was performed, in the second case laparoscopy and then laparotomy due to massive
      adhesions were performed. RESULTS: In both cases histopathological examinations
      showed: cystis picea endometriotica ovarii. Both patients delivered at term.
      CONCLUSIONS: Ovarian endometriomas does not exclude fertility. Surgical
      management of ovarian endometriomas does not complicate pregnancy course.

PMID- 11526778
TI  - [Rapidly growing endometrial cyst of the uterus in a young woman].
AB  - A case of a rapidly growing endometriotic cyst of uterus in young women diagnosed
      for sterility, and previously treated by GnRH analogues was presented. The case
      was difficult to diagnose before the operation.

PMID- 11526779
TI  - [The implantation of bipolar coagulation to remove endometriosis foci].
AB  - The paper compares the results of bipolar coagulation bey means of ERBE ICC 300
      diatermy coagulator and WISAP endocoagulator. The results of both types of
      coagulation were assessed with reference to the changes occurring on peritoneum
      ligamenti sacro-uterini, Douglas pouch and ovary. The best results of
      endometriosis foci coagulation were obtained with bipolar ball at 20-30 W; no
      side effects or feelings of malaise were observed in patients just after the
      operation or over a longer period of convalescence.

PMID- 11526780
TI  - [Transvaginal hydrolaparoscopy].
AB  - The paper presents a simple and cheap method of transvaginal hydro-laparoscopy
      used for the observation women pelvic organs. The method may be useful to
      diagnose sterility, indefinite pains the pelvis or to control the patients
      previously undergoing operations. Hydro-laparoscopy was carried out in 12
      patients by means of a modified 3 mm hysteroscope equipped with modified Verres
      needle. The method worked successfully in 10 cases. The quality of the endoscopic
      pictures od pelvic organs was satisfactory. No complications during the operation
      or convalescence were observed.

PMID- 11526781
TI  - [Pregnancy and delivery in women after endometriosis treatment].
AB  - The study was done in Clinic of Pathology Pregnancy in A.M. in Lodz in 1998-2000
      y. The first group consist of women after endometriosis treatment--30, the second
      -30 healthy pregnant women. The course of pregnancy and delivery was observed.
      High rate of: women over 35 years old, preterm delivery, cervical insufficiency
      treated surgically, caesarean sections rate were observed in group of women after
      endometriosis treatment. There was no difference at neonatal state between
      groups.

PMID- 11526782
TI  - [Ultrasonographic assessment of pregnancy development after endometriosis
      treatment].
AB  - Investigated group comprised pregnant women after sterility treatment, which
      underwent obstetrical care in Institute of Obstetrics and Gynaecology Medical
      Academy of Lodz in years 1998-2000. In the first group were 25 pregnant women
      after endometriosis treatment, the second one 23 healthy pregnant women. At term
      were performed ultrasound examinations (biometry and estimated fetal weight) than
      were assessed neonatal weight in both groups. There were found the similar mean
      age in both groups, but in the group after treatment more women in age over 30
      years were observed (not significant). The higher weights were observed in the
      group of healthy pregnant women in ultrasound fetal estimation before delivery
      (about 343.5 g) and neonatal weight after delivery (about 407 g) but without
      significance. There is possibility of the better vascular development in the feto
      maternal circulation in the course of pregnancy in healthy women than after
      endometriosis treatment, but for the correct conclusions should be made further
      research on larger collectives. Ultrasound assessment is a useful method in
      prenatal diagnostic with possibility of precise analysis of the fetal
      development.

PMID- 11526783
TI  - [The assessment of dendritic cells cultured from peritoneal fluid macrophages:
      first report and new perspectives in the treatment of endometriosis].
AB  - Dendritic cells represent discrete leukocyte subpopulation of specialist or
      "professional" antigen-presenting cells (APC). They play a crucial role in the
      activation of naive T cells "in vivo" They have monocyte/macrophages origin.
      There are no data in literature on the presence of dendritic cells derived from
      peritoneal fluid monocytes/macrophages. In our study we tried to culture PF
      macrophages from patients who undergone surgery so that to obtain dendritic
      cells. PF was aspirated during laparoscopy from patients with endometriosis,
      unexplained infertility or benign noninflammatory ovarian tumor. Peritoneal
      macrophages were isolated using adherence method then were cultured and
      stimulated with GM-CSF and IL-4. Phenotype of cultured cell was estimated using
      flow cytometry after incubation with monoclonal antibodies CD45/14, CD 40/HLA-DR,
      CD28/3, CD3/40L, CD25/5 and CD69/HLA-DR. Morphology of cultured cells was
      confirmed microscopically after May-Grunvald-Giemsa staining. PF leukocytes
      concentration varied from 1.2 x 10(6) cells/mm3 to 22.6 x 10(6) cells/mm3.
      Cultured monocytes/macrophages from PF had morphology typical for dendritic
      cells. We also found that only dendritic cells from patients with endometriosis
      had higher expression HLA-DR antigen (93.6% of cells) and low expression of CD40
      (2.7% of cells) on their surface in comparison to reference group. It is worthy
      to notify that dendritic cells from patients with endometriosis expressed also
      CD25 antigen characteristic for T leukocytes. To our data it is the first report
      in literature on dendritic cells obtained from PF macrophages.

PMID- 11526784
TI  - [Phagocyte activity of macrophages in the peritoneal fluid of patients with
      endometriosis].
AB  - Phagocytic activity of macrophages isolated from peritoneal fluid (PF) was
      estimated using flow cytometry. Study group consists of 28 patients with
      endometriosis and 19 patients with benign noninflammatory tumour of adnex(is)
      served as reference group. Macrophages were processed in two ways: fresh cells
      were obtained from women with endometriosis (n = 7) and reference group (n = 10)
      and frozen cells derived from patients with endometriosis (n = 21) and reference
      group (n = 9). Phagocytic activity of macrophages was measured against opsonized
      and conjugated with FITC E. coli. It is worth to notify that phagocytosis was
      determined in PF environment in the study. Percentage of phagocytosing fresh
      macrophages did not differ (p = 0.05) between subjected groups of patients and
      was respectively 64.3% +/- 17.3% vs 49.0 +/- 4.0%. Phagocytic activity of frozen
      macrophages derived from patients with endometriosis was significantly higher (p
      < 0.02) in comparison to reference group (14.3 +/- 9.1% vs 5.2 +/- 2.8%).

PMID- 11526785
TI  - [The evaluation of IL-12 levels in peritoneal fluid and serum of women with
      endometriosis].
AB  - We studied levels of IL-12 in peritoneal fluid and serum in patients with
      minimal, advanced and recurrent endometriosis compared to women without
      endometriotic lesions in pelvis minor. The aim of the study was to determine
      whether level of IL-12 detected in peritoneal fluid or serum changes with grading
      of severity of endometriosis. To assess IL-12 levels immunosorbent ELISA was
      used. There were no statistically significant differences in IL-12 levels in
      peritoneal fluid nor in serum in any of studied groups. There was higher
      concentration (without statistical significance) of IL-12 in peritoneal fluid of
      healthy women compared to women with endometriosis.

PMID- 11526786
TI  - [E-cadherin in the serum and the peritoneal fluid of women with endometriosis].
AB  - Endometriosis, a disease of unclear etiopathogenesis, is a quite common problem
      in gynecology. It is thought that the retrograde flow of the menstrual debris to
      the peritoneal cavity plays an important role in the origin of endometriosis but
      the mechanism of endometrial cells implantation remains unknown. Recently many
      centers have reported the importance of adhesion molecules in this process. We
      studied the concentrations of E-cadherin in the serum and the peritoneal fluid of
      women with endometriosis. Our results show a significant decrease of E-cadherin
      concentrations in sera and peritoneal fluids in women with endometriosis. We
      suggest that screening the level of E-caherin may be useful in the monitoring the
      therapy of endometriosis.

PMID- 11526787
TI  - [Lipid peroxides, tumor necrosis factor alpha (TNF-alpha) and interferon gamma
      (IFN-gamma) in peritoneal fluid from infertile women with minimal and mild
      endometriosis].
AB  - OBJECTIVES: To assess the concentrations of tumor necrosis factor alpha (TNF
      alpha), interferon gamma (IFN-gamma) and lipid peroxides (the marker of free
      radicals activity) in peritoneal fluid (PF) of infertile women with minimal and
      mild endometriosis. MATERIALS AND METHODS: 19 women were studied, including 9
      infertile women with minimal or mild endometriosis and 10 patients with tubal
      occlusion (the reference group). Lipid peroxides (malonyldialdehyde and 4
      hydroxynonenal), TNF-alpha and IFN-gamma concentrations were measured in the PF
      using commercially available kits. RESULTS: Concentration of IFN-gamma was
      detectable in PF of 7 (77.8%) women with endometriosis and in PF from 3 (30%)
      patients with tubal occlusion. Neither TNF-alpha or lipid peroxides PF
      concentration differed significantly (p < 0.05) between the groups. In the group
      with endometriosis we have found a positive correlation (R = 0.77, p = 0.04)
      between the concentrations of TNF-alpha and IFN-gamma. CONCLUSIONS: Our results
      suggest that oxidative stress in the PF doesn't appear to play a role in
      endometriosis-associated infertility.

PMID- 11526788
TI  - [VEGF, TNF-alpha and IL-6 in the peritoneal fluid of women with unexplained
      infertility].
AB  - Unexplained infertility is an important problem in diagnosis and therapy in
      everyday gynecologist's practice. Looking for possible reasons of the unexplained
      infertility we studied the concentrations of selected cytokines (VEGF, TNF-alpha
      and IL-6) in the peritoneal fluid of women suffering from the unexplained
      infertility. We compared the results in the studied group with the control group
      and with the patients with endometriosis. Immunological disorders of the
      peritoneal fluid in endometriosis are thought to take part in its pathomechanism.
      Our results suggest that the levels of one of the main factors of endothelium
      proliferation (VEGF) in the peritoneal fluid from women with unexplained
      infertility and women with endometriosis are comparable. Concentration IL-6 and
      TNF-alpha in the peritoneal fluid in case of unexplained infertility and control
      group was lower than in the endometriosis patients.

PMID- 11526789
TI  - [Evaluation of peripheral blood neutrophils activity in women with
      endometriosis].
AB  - Authors evaluated the neutrophils ability of creating reactive oxygen
      intermediates (ROI) in peripheral blood of 14 patients with endometriosis. These
      tests were performed using the chemiluminescence method. Enhanced ROI production
      and in vivo priming phenomenon of neutrophils in endometriosis were reported. The
      observed increase in oxygen activity of neutrophils was statistically significant
      only in reaction with the use of fMLP. However performed neutrophils
      preactivation with TNF-alpha followed by the chemiluminescence test revealed the
      occurrence of in vivo neutrophil activation in women with endometriosis. Reported
      data confirm the existence of local inflammatory reaction in the course of
      endometriosis.

PMID- 11526790
TI  - [Evaluation of the generation of interleukin-10 by peripheral blood lymphocytes
      in women with endometriosis].
AB  - The aim of study was the evaluation of generating the IL-10 by peripheral blood
      lymphocytes in women with endometriosis according to the stage of of the disease.
      Cytokine was estimated by immunoenzymatic method Elisa. The generation of IL-10
      by peripheral blood lymphocytes was lower in patients with all stages of
      endometriosis than in control group. Decreased IL-10 generating observed in our
      study was not statistically significant, but it may correlate with disorders of
      immunological cell response. It may also play a role in a development and
      progression of endometriosis.

PMID- 11526791
TI  - [VEGF concentration in peritoneal fluid of patients with endometriosis].
AB  - The theory of Sampson that endometrial cells and fragments desquamated during the
      menstrual period are transported through fallopian tubes into the peritoneal
      cavity where they implant, proliferate and develop into endometriotic lesions is
      generally accepted. There is increasing evidence that immunological mechanisms
      play a role in the pathogenesis and pathophysiology of endometriosis. Excessive
      endometrial angiogenesis is proposed as an important mechanism in the
      pathogenesis of endometriosis. Evidence is reviewed for the hypothesis that the
      endometrium of women with endometriosis has an increased capacity to proliferate,
      implant and grow in the peritoneal cavity. From the known angiogenic factors,
      vascular endothelial growth factor (VEGF) has emerged as a pivotally important
      regulator of normal angiogenesis and pathological neovascularization. In present
      study we evaluated the concentrations of VEGF in peritoneal fluid of patients
      with endometriosis and showed no correlation between AFS score and VEGF
      concentration in peritoneal and in ovarian endometriosis. Above results do not
      confirm former observations indicating the role of VEGF in endometriosis
      pathogenesis.

PMID- 11526792
TI  - [Subjective response to neuroleptic medication: a validation study of the Italian
      version of the Drug Attitude Inventory (DAI)].
AB  - OBJECTIVE: Aim of the study was to investigate the psychometric properties of the
      Italian version of the Drug Attitude Inventory (DAI) by exploring its construct
      validity. SETTING: 90 voluntary admitted patients with DSM III-R Schizophrenic
      (n.72) and Schizoaffective (n.18) disorders, age range between 18 and 50 years,
      treated with typical antipsychotics, able to participate in the study, were
      selected. DESIGN: Exploratory factor analyses with alpha factoring and maximum
      likelihood methods with Varimax Rotation were used to analyse DAI scores.
      RESULTS: Extraction methods found 7 factors which explained 62.5% of the total
      variance. The first 2 factors could be labelled as "subjective response to
      treatment" construct and factors 3 to 7 as "attitude to medication" construct.
      CONCLUSION: Although preliminarily, the Italian version of the DAI seems to
      maintain the original psychometric properties and it can be used easily to get a
      valid measurement of the patients' attitude to neuroleptic medication.

PMID- 11526793
TI  - [Analysis and comparative evaluations of the costs of supports and treatments of
      schizophrenia, affective psychosis, paranoia and neurosis].
AB  - OBJECTIVE: The aim of the study was to show, trough the calculation of the direct
      costs of supports and treatments actually provided by a NHS Mental Health
      Department, the presence of associations between four diagnostic groups
      (schizophrenia, affective psychosis, paranoia and neurotic disorders) and their
      overall and items (community care, rehabilitation facilities and in-patients
      services) costs. SETTING: Mental Health Department and CSM "Scalo" (NHS Mental
      Centre), AUSL "Citta di Bologna", Emilia-Romagna Region. DESIGN: Yearly direct
      costs were calculated for a sample (n = 75) of all patients (N = 745) who during
      365 days had more than four contacts with CSM and also for four randomised
      diagnostic groups (n = 30 per group). MAIN OUTCOME MEASURES: We calculated unit
      costs of 15 types of services provided by CSM, selected according to the yearly
      number of services provided and the time spent by each health professional, and
      the in patient-cost per all days spent in a public or private sector hospital for
      psychiatric care. RESULTS: The statistic analysis, performed with the help of the
      Kruskal-Wallis test, showed significantly higher overall costs for the
      schizophrenic patients than the sample-group and the neurotic disorders-group;
      besides a significant difference in the item costs for rehabilitation facilities
      was found between the schizophrenic group and the paranoia, neurotic disorders
      groups and the sample one, whereas no significant differences in costs of
      inpatients services and drugs administration were tested between the groups.
      CONCLUSIONS: The results of our study allow to demonstrate that there are cost
      differences between the diagnosis (direct costs are highest for schizophrenic
      patients and lowest for those with neurotic disorders) and that the costs
      evaluation can be used to ensure appropriate provisions to Mental Health
      Department for support and treatment of a wide range of psychiatric disorders.

PMID- 11526794
TI  - [Predicting length of stay in Italian Psychiatric Forensic Hospitals: a survival
      analysis].
AB  - Admission to an Italian Forensic Hospital (OPG) results in formal exit from
      psychiatric care provided by NHS community based psychiatric services. The length
      of stay in such facilities is often perceived as a factor negatively affecting
      the opportunity for reintegration in the community. METHOD: Factors predicting
      length of stay in OPG were investigated by means of a survival analysis carried
      out on a cohort of 118 inmates of three OPGs (Castiglione delle Stiviere, Reggio
      Emilia and Montelupo Fiorentino), who represent the whole forensic population
      from 3 different geographical areas at 30.06.97; all discharges occurred in the
      following 18 months were examined. RESULTS: In survival analyses conducted on
      individual predictors, five variables predicted a longer stay: type of offenses
      (homicide: 706.6 weeks vs. 307.1 for minor offenses and 194.7 for grievous bodily
      harm, log-rank = 31.8, p < 0.001), type of admission (RR = 0.98, CI 95% 0.97
      0.99, p < 0.001), the diagnosis of schizophrenia (621.9 weeks vs. 398.9 weeks or
      less for other diagnoses; log rank = 9.08, df = 3, p = 0.028), BPRS thought
      disturbance score (RR = 0.89, CI 98% 0.81-0.98, p < 0.01), hospital of stay
      (314.6 weeks in Montelupo Fiorentino vs. 706.6 for Reggio Emilia and 621.9 for
      Castiglione delle Stiviere; log-rank = 9.64, df = 2, p < 0.001). In a Cox linear
      regression model three significant factors were selected: type of offenses stype
      of admission, diagnosis of schizophrenia. CONCLUSIONS: Judicial factors are
      relevant in determining the length of stay in OPG. The diagnosis of schizophrenia
      seems to play an independent role in predicting a longer stay.

PMID- 11526795
TI  - [New trends in drug addiction: synthetic drugs. Epidemiological, clinical and
      preventive issues].

PMID- 11526796
TI  - Alcohol policy as a public health issue. Reconsidering an old concept and its
      relevance for mental health.

PMID- 11526797
TI  - Drug treatment service provision in the UK: policy comprehensiveness versus
      practice effectiveness.

PMID- 11526798
TI  - Analysis of patterns of mental health care with three different approaches (cross
      sectional, longitudinal and dynamic).
AB  - OBJECTIVE: This article attempts to provide an overview of different methods of
      analysis of information on service utilization from different approaches.
      METHODS: A systematic review of the studies of pattern of care is done. The
      analysis of pattern of care has been divided into three different approaches:
      cross-sectional, longitudinal and dynamic. RESULTS: In cross-sectional studies,
      information on utilization is based on the total number of contacts with mental
      health services during a given period. In the second approach, called
      longitudinal, survival analysis is applied considering the interval of time
      between each contact. The third type of analysis, called here the "dynamic"
      approach, involves the application of mathematical models based on the Markov
      chain to analyse the probability of change from one type of contact to another.
      CONCLUSIONS: We emphasise the need for further studies designed to analyse data
      from psychiatric case registers with standardised models for mental health
      services utilization analysis.

PMID- 11526799
TI  - [Post-partum as a specific risk factor for the onset of obsessive-compulsive
      disorder: clinical-controlled study].
AB  - OBJECTIVE: The aim of this study is to evaluate the presence of triggering life
      events for the onset of Obsessive-Compulsive Disorder in women (OCD). DESIGN:
      Clinical controlled study. SETTING: Service for depressive and anxiety disorders;
      Department of Neuroscience, Psychiatric Unit, University of Turin. METHODS: The
      study compares twenty-nine women with OCD (DSM-IV criteria) with twenty-nine
      healthy control women matched for demographic features and with twenty-nine women
      with Bulimia Nervosa (DSM-IV criteria) matched for age, age at onset, education
      and marital status. All patients were assessed with the Clinical Structured
      Interview for DSMIII-R (SCID) and with the Interview for Recent Life Event by
      Paykel. Moreover, OCD patients were assessed with the Yale-Brown Obsessive
      Compulsive Scale (Y-BOCS) and bulimic patients with the Eating Disorder Inventory
      (EDI). RESULTS: The study demonstrates that the only specific life event that is
      significantly associated with the onset of OCD is "having a new born child" No
      significant differences in frequency and severity of stressing life events were
      found in the three groups. CONCLUSIONS: The results confirms the findings of our
      previous study: post partum is the only risk factor for the onset of OCD in
      female population, compared to healthy control. Furthermore, this research points
      out the importance and the specificity of this association showing that post
      partum is not a risk factor in all psychiatric disorders.

PMID- 11526800
TI  - [The condition of families of patients with schizophrenia in Italy: burden,
      social network and professional support].
AB  - OBJECTIVE: This study aimed to describe: a) the interventions received by
      patients with schizophrenia attending Italian mental health services (MHS); b)
      the relatives' burden and social network and the professional support received by
      the families. DESIGN: The study has been carried out in 30 MHS, randomly selected
      and stratified by geographic areas and population density. 25 patients with a DSM
      IV diagnosis of schizophrenia and 25 relatives were recruited in each MHS. Family
      burden was evaluated in relation to: a) geographic area; b) interventions
      received by the patients; c) social and professional support received by the
      families. MAIN OUTCOME MEASURES: a) patients: Brief Psychiatric Rating Scale
      (BPRS) and Disability Assessment Interview (AD); b) key-relatives: Family
      Problems Questionnaire (QPF) and Social Network Questionnaire (QRS); c)
      interventions received by the patients and their families: Scheda di Rilevazione
      degli Interventi--Pattern of Care Schedule (SRI). RESULTS: Data on 709 patients
      and their key-relatives were collected. In the two months preceding the data
      collection, 35% of patients attended rehabilitative programmes; 80% of the
      families were in regular contact with the MHS and 8% received family
      psychoeducational interventions. Family burden was higher in Southern than in
      Central and Northern Italy. This difference disappeared when rehabilitative
      interventions and family support were provided. CONCLUSIONS: This study
      highlights that the situation of the families of patients with schizophrenia is
      more burdensome in Southern Italy and is greatly influenced by the type of
      interventions provided by the MHS.

PMID- 11526801
TI  - Etonogestrel implant (Implanon) for contraception.
AB  - Levonorgestrel 38 mg subdermal implant (Norplant), intended to provide
      contraception for 5 years, was withdrawn in the UK in 1999 due to unwanted
      effects (menstrual disturbances) and difficulties in removing the device. Since
      then, [symbol: see text]etonogestrel implant (Implanon-Organon), another
      progestogen--only subdermal contraceptive device, has become available in the UK.
      The manufacturer claims that etonogestrel implant provides contraception for up
      to 3 years and is easy to insert and remove. Here, we consider the place of
      etonogestrel implant.

PMID- 11526802
TI  - Managing incontinence due to detrusor instability.
AB  - Urinary incontinence affects around 3.5 million people of all ages in the UK. For
      many, incontinence severely restricts their routine activities and damages their
      quality of life and self-esteem. In about one-third of women sufferers, and
      around a half of all men with incontinence, the cause is detrusor instability.
      This condition is characterised by involuntary bladder contractions or pressure
      rises during bladder filling, which result in a strong or uncontrollable urge to
      pass urine and, often, incontinence. Here, we consider a primary care-based
      approach to managing urinary incontinence in adults, concentrating on the medical
      management of detrusor instability.

PMID- 11526803
TI  - The contributions of health economics to mental health policy.

PMID- 11526804
TI  - Using financial incentives to promote shared mental health care.
AB  - OBJECTIVES: To consider the most common primary care reimbursement structures, to
      identify incentives inherent in each, and to discuss how each could be used to
      encourage a shared-care approach to treating mental disorders at the primary care
      level. METHOD: Three major financial reimbursement models--fee-for-service,
      capitation, and blended payment mechanisms--are examined. Each is considered in
      terms of its risk-sharing elements and the consequent incentives. We offer
      several scenarios to illustrate how the shared-care practice model might be
      encouraged under each financing mechanism. RESULTS: The current fee-for-service
      system does not encourage shared care. For wide adoption of the shared-care
      practice model, there must be a change in the reimbursement system's incentives.
      While none of the financing mechanisms offers a perfect solution, each has
      potential. Each, however, must be carefully tailored to its environment.
      CONCLUSIONS: Financial considerations are just one aspect to achieving shared
      care. Nevertheless, in designing a system to encourage collaborative, coordinated
      care for those suffering from mental illness, decision makers should be wary of
      creating or maintaining obstacles (financial or otherwise) to provision of
      accessible, high-quality care.

PMID- 11526805
TI  - Economic impacts of supported employment for persons with severe mental illness.
AB  - BACKGROUND: Most persons with severe mental illness prefer competitive to
      sheltered vocational settings. Supported employment (SE) has become a clearly
      defined model for helping people with severe mental illness to find and maintain
      competitive jobs. It involves individualized and rapid placement, ongoing support
      and assessment, and integration of vocational and mental health staff within a
      single clinical team. Previous studies show that SE secures competitive
      employment much more effectively than do other approaches. This review focuses on
      its economic impacts. METHODS: Studies reporting some service use or monetary
      outcomes of adding SE programs were identified. These outcomes were tabulated and
      are discussed in narrative form. RESULTS: Five nonrandomized and 3 randomized
      studies compare SE programs with day treatment or transitional employment
      programs. The introduction of SE services can result in anything from an increase
      to a decrease in vocational service costs, depending on the extent to which they
      substitute for previous vocational or day treatment services. Overall service
      costs tend to be lower, but differences are not significant. Earnings increase
      only slightly on average. CONCLUSIONS: Converting day treatment or other less
      effective vocational programs into SE programs can be cost-saving or cost-neutral
      from the hospital, community centre, and government points of view. Investments
      of new money into SE programs are unlikely to be materially offset by reductions
      in other health care costs, by reductions in government benefit payments, or by
      increased tax revenues. Such investments must be motivated by the value of
      increasing the community integration of persons with severe mental illness.

PMID- 11526806
TI  - Mild dementia or cognitive impairment: the Modified Mini-Mental State examination
      (3MS) as a screen for dementia.
AB  - OBJECTIVE: To examine the Modified Mini-Mental State Examination (3MS) as a
      screen for dementia. METHOD: A group of 1092 elderly Edmonton community residents
      completed the 3MS and the Geriatric Mental State Examination (GMS). 3MS
      sensitivity and specificity were determined by comparing positive 3MS screens
      (score < or = 77) with those classified as GMS "organic" (severity level 3,
      equivalent to a clinical diagnosis). In the Canadian Study of Health and Aging
      (CSHA), 2914 subjects received the 3MS and a clinical examination. A group
      described as having "cognitive impairment but no dementia (CIND)" was identified.
      RESULTS: In Edmonton, the 3MS showed 88% sensitivity, 90% specificity, 29%
      positive predictive value (PPV), and 99% negative predictive value (NPV). In the
      CSHA, 30% of subjects receiving both the 3MS and a clinical examination were
      classified as CIND. One-half of these were classified as having "age associated
      memory impairment (AAMI)" or as "unspecified." CONCLUSIONS: The 3MS with a
      cutting score of 77/78 proved a reasonable screening instrument; 1 case in 3
      screening "positive" has dementia, but few (0.64%) will be missed by screening
      "negative." CIND, accounting for 2 out of 3 cases screened positive by the 3MS in
      the Edmonton study, is a substantial, heterogeneous group that is not necessarily
      "predementia" but that in many cases merits further investigation.

PMID- 11526807
TI  - [Schizophrenia and cognitive behavioral psychotherapy].
AB  - OBJECTIVE: To distinguish between different approaches of cognitive-behavioural
      therapy (CBT) for schizophrenia depending on the goals, objectives and methods of
      these approaches, then to discuss efficacy studies. METHOD: A summary of
      information collected through electronic (MEDLINE, PSYchlit) and bibliographic
      research. RESULTS: CBTs all broadly attempt to bring a better cognitive,
      behavioural and emotional adjustment to the psychotic experience by suggesting to
      the patient a new explanatory model of psychosis: the vulnerability-stress model.
      These approaches involve different levels and goals. Some focus on correcting
      basic cognitive deficits or modifying the psychotic symptoms and the related
      distress. At the other end of the spectrum, metacognitive therapies aim to modify
      and restructure dysfunctional self and environment schemas to enable the
      development of better-adjusted and generally applied cognitive strategies. A few
      studies with limited power and methods have shown the efficiency of those
      therapies. CONCLUSION: CBTs prove to be a promising additive treatment. They have
      been shown to improve social adjustment and quality of life, and to diminish
      psychotic symptoms and the related distress. They address all positive, negative,
      cognitive, behavioural, and emotional symptoms while considering the stage of the
      disease and the patient's special needs. Further research is needed to establish
      the duration, the best provision frequency, and the specificity of these
      approaches.

PMID- 11526808
TI  - Polydipsia, psychosis, and familial psychopathology.
AB  - OBJECTIVE: To compare the demographic and clinical factors and familial
      psychopathology of chronic psychiatric inpatients with, and without, polydipsia.
      METHOD: We undertook a case-control study of chronic psychiatric inpatients both
      with, and without, polydipsia. Clinical and demographic data were gathered using
      a predesigned questionnaire, the Positive and Negative Syndrome Scale (PANSS),
      the Abnormal Involuntary Movement Scale (AIMS), the Mini-Mental State Examination
      Scale (MMSE), and the Family History-Research Diagnostic Criteria (FH-RDC).
      RESULTS: The prevalence rate of polydipsia was 20.2%. The group with polydipsia
      was significantly younger, both at the time of their first-ever psychiatric and
      current psychiatric admissions, compared with the group without polydipsia. The 2
      groups were similar in terms of their illness characteristics and psychiatric
      diagnoses. In the group with polydipsia, alcohol abuse predated the psychotic
      illness by a mean of 10.5 (SD 4.4) years, compared with 4.8 (SD 1.6) years for
      the same period in the unaffected group. The 2 groups did not differ
      significantly regarding the antipsychotic medication dosage, the proportion on
      concomitant anticholinergic medication, the documented previous response to
      antipsychotic medication, or past treatment with electroconvulsive therapy (ECT).
      First-degree relatives of patients with polydipsia were found to have
      significantly higher rates of alcohol dependence. CONCLUSION: This study provides
      further evidence for the higher rate of polydipsia among chronic psychiatric
      patient populations and for high rates of alcohol-related problems among their
      first-degree relatives.

PMID- 11526809
TI  - Alternative medicine use by individuals with major depression.
AB  - OBJECTIVE: To describe the use of alternative medicine (AM) by persons with major
      depression and to examine the factors associated with AM use among these
      individuals. METHODS: We used data from the 1994-1995 and 1996-1997 National
      Population Health Surveys. We selected subjects who had major depression
      according to the Composite International Diagnostic Interview Short Form for
      Major Depression (CIDI-SFMD). The prevalence of AM and conventional health
      service use by the subjects was calculated for each survey and was stratified by
      province. We employed logistic regression to examine the factors associated with
      AM use. RESULTS: There was a temporal trend toward increasing use of AM among
      persons with major depression. The prevalence of AM use among subjects with major
      depression was 7.8% in 1994-1995 and 12.9% in 1996-1997. Female sex, having more
      than 12 years' education, and having 1 or more long-term medical conditions were
      associated with an increased likelihood of using AM. The sex difference in AM use
      depended on subjects' age in 1996-1997. CONCLUSION: General practitioners, mental
      health specialists, and AM providers should be aware of their patients' use of
      both conventional medical services and AM because there may be interactions
      between conventional and alternative treatments. Communication and, if possible,
      cooperation may lead to improved outcomes in the management of depressive
      disorders.

PMID- 11526810
TI  - Risperidone treatment of outpatients with schizophrenia: no evidence of sex
      differences in treatment response.
AB  - OBJECTIVE: Given the renewed interest in the role of sex differences in
      schizophrenia, we undertook a post hoc analysis to determine whether sex
      differences in treatment response were present among outpatients with
      schizophrenia who received risperidone in an 8-week, open-label, Phase IV
      clinical study. METHOD: We evaluated 330 adult patients (232 men, 98 women) with
      a DSM-III-R diagnosis of schizophrenia for safety and 292 (206 men, 86 women) for
      efficacy. Antipsychotic and antiparkinsonian medications were discontinued at
      study entry. Treatment with risperidone was initiated at a dosage of 2 mg daily,
      increased to the target dosage of 6 mg daily by day 3, and maintained at 6 mg
      daily until day 14. The dosage was then maintained at 6 mg daily, increased or
      decreased by 2 mg daily each week, based on the patient's response. Risperidone
      treatment was given for 8 weeks; the permitted dosage range was 4 mg to 10 mg
      daily. RESULTS: Both male and female participants responded well to risperidone
      treatment; by the final assessment day, they had experienced decreases from
      baseline in their total Positive and Negative Syndrome Scale (PANSS) scores of
      41.0% and 36.5%, respectively. Most male (77%) and female (78%) participants were
      considered to be PANSS responders: risperidone was effective against both the
      positive and negative symptoms of schizophrenia. Both sexes showed improvements
      over baseline in the incidence and severity of parkinsonism, dystonia, and
      dyskinesia. No significant (P > 0.05) sex differences in treatment response were
      observed for any of the efficacy outcomes or in the incidence and severity of
      extrapyramidal symptoms (EPS). CONCLUSIONS: In this population of outpatients
      with chronic schizophrenia, both men and women responded well to flexible doses
      of risperidone. No significant sex differences were evident either in treatment
      response or in neurological side effects. The absence of sex differences in
      response to risperidone treatment may obviate the need for a sex-based
      differential dosing in schizophrenia management.

PMID- 11526811
TI  - Pre-, peri-, and postnatal trauma in subjects with attention-deficit
      hyperactivity disorder.
AB  - OBJECTIVE: To review research on pre-, peri-, and postnatal stress and their
      potential relation to attention-deficit hyperactivity disorder (ADHD). METHOD: We
      selected and critically reviewed 51 research reports from the medical and
      psychology literature, between January 1, 1976 and May 1, 2001, based on the
      subjects of pre-, peri-, or postnatal stress and ADHD. RESULTS: Children with
      ADHD show higher percentages of pre-, peri-, or postnatal insult, compared with
      unaffected children; however, the relative influence of various factors is still
      controversial. CONCLUSIONS: The etiology of ADHD encompasses genetic and
      environmental factors. Pre-, peri-, and postnatal stressors are environmental
      factors that may play a role in its etiology. Future research should carefully
      examine interactions between genetic predisposition and environmental factors as
      etiologies of ADHD.

PMID- 11526812
TI  - Body mass index in persons with schizophrenia.
AB  - BACKGROUND: Schizophrenia has been associated with several health concerns and
      risks. Overall mortality among persons with schizophrenia has been shown to be
      about twice that of the general population. There is growing concern that persons
      with schizophrenia may also be at risk for being overweight or obese, compared
      with the general population. To examine this possibility, the author compared the
      distribution of body mass index values (BMI = kg/m2) in people with schizophrenia
      with that of the Canadian population as a whole. METHOD: Weights and heights were
      obtained for 183 patients receiving treatment in a hospital-based program for
      persons with schizophrenia. These BMI values were compared with the results of
      Statistics Canada's 1996-1997 National Population Health Survey (NPHS), which
      provided average BMI values for the general population. RESULTS: The average BMI
      in the study sample was 29.02, with the average for men being 28.49 (range 15.55
      to 49.22, SD 6.25) and the average for women, 30.02 (range 19.30 to 45.71, SD
      6.45). This is compared with the NPHS average BMI of 26.3 for men and 24.3 for
      women. The prevalence of obesity (BMI > 30) in the sample was 42.08%, 3.5 times
      that of the Canadian average of 12% and 2.8 times that of the 15% prevalence in
      Manitoba. In this sample, 26.78% had a BMI in the acceptable range, in contrast
      to the 48% of those in the NPHS who had a weight appropriate to their height.
      CONCLUSIONS: This analysis provides evidence that the BMI distribution of the
      sample population is different from that of the national population as
      represented in the NPHS data. The data indicate that patients with schizophrenia
      are significantly heavier than the general population.

PMID- 11526813
TI  - Re: The neurobiology, neuropharmacology, and pharmacologic treatment of
      paraphilias and compulsive sexual behaviour.

PMID- 11526814
TI  - Open-label risperidone treatment of 6 children and adolescents with autism.

PMID- 11526815
TI  - Bupropion and drug-induced parkinsonism.

PMID- 11526816
TI  - Re: Training residents for community psychiatric practice--the resident
      perspective.

PMID- 11526817
TI  - Metamorphosis of delusion of pregnancy.

PMID- 11526818
TI  - Home visits from an outpatient psychiatric clinic.

PMID- 11526819
TI  - Clinical characteristics of delusional disorder.

PMID- 11526820
TI  - Sexual aversion disorder treated with behavioural desensitization.

PMID- 11526821
TI  - [Comparative study of the activity of hyaluronic acid and dextranomer in the
      treatment of leg ulcers of venous origin].

PMID- 11526822
TI  - [Role of dressings with hyaluronic acid base in the treatment of leg ulcers].

PMID- 11526823
TI  - [Hyaluronic acid].

PMID- 11526824
TI  - [Physiopathology of normal cutaneous cicatrization and in leg ulcer].

PMID- 11526825
TI  - [Pharmacological properties of hyaluronic acid].

PMID- 11526826
TI  - The effects of external sodium and potassium concentration on the membrane
      potential of atrioventricular fibers of the toad.
AB  - Intracellular records were made from fibers in the A-V conducting system of
      isolated toad hearts. The A-V region was perfused with Ringer's solution of
      various K and Na concentrations. Resting potential in 2.8 mM [K]o was about 60
      mv. Over the range 0.28 to 28 mM, resting potential diminished with increasing
      [K]o. Spontaneous action potentials appeared when [K]o was increased to 11.2 mM,
      and when resting potential had fallen to about 40 to 50 mv. Changes in [Na]o over
      the range 22 to 110 mM had a little effect on resting potential, but there was a
      linear relation between the peak value of the action potential and log [Na]o.
      Wenckebach periodicity was observed when [Na]o was lowered.

PMID- 11526827
TI  - Ca fluxes in single twitch muscle fibers.
AB  - Ca influx and efflux in single twitch muscle fibers were determined by the
      movement of 45Ca. The isotope was assayed by counting the center 1 cm of a fiber
      while it was in nonradioactive Rnger's solution. The average resting influx in
      1.0 mM Ca Ringer's was 0.26 pM Ca/cm2. sec for 5 to 20 min influx periods. The
      average additional influx upon stimulation in 1.0 mM Ca was 0.73 pM Ca/cm2.
      twitch. The efflux after both resting and stimulated 45Ca influx can be described
      by a single exponential curve with an average time constant of 125 min. This
      relationship is an indication of Ca exchange with a single intracellular
      compartment. This compartment contains an estimated 47% of the total muscle Ca at
      1.0 mM Ca. When the Ca in the Ringer was reduced to 0.5 mM Ca, both the resting
      and stimulated Ca fluxes decreased. When Ca was raised to 1.8 mM, the stimulated
      influxes increased but the resting influx did not.

PMID- 11526828
TI  - Long duration responses in squid giant axons injected with 134cesium sulfate
      solutions.
AB  - Giant axons from the squid were injected with 1.5 M cesium sulfate solutions
      containing the radioactive isotopes 42K and 134Cs. These axons, when stimulated,
      gave characteristic long duration action potentials lasting between 5 and 45
      msec. The effluxes of 42K and 134Cs were measured both under resting conditions
      and during periods of repetitive stimulation. During the lengthened responses
      there were considerable increases in potassium efflux but only small increases in
      cesium efflux. The selectivity of the delayed rectification process was about 9
      times greater for potassium ions than for cesium ions. The data suggest that
      internal cesium ions inhibit the outward potassium movement occurring during an
      action potential. The extra potassium effluxes taking place during excitation
      appear to be reduced in the presence of cesium ions to values between 7 and 22%
      of those expected in the absence of cesium inhibition.

PMID- 11526829
TI  - Voltage clamp studies on the effect of internal cesium ion on sodium and
      potassium currents in the squid giant axon.
AB  - Isolated and cleaned giant axons of Loligo pealii were internally perfused with
      solutions containing cesium sulfate and potassium fluoride. Membrane currents
      obtained as a function of clamped membrane potentials indicated a severe
      depression of the delayed outward current component normally attributed to
      potassium ion movement. Steady-state currents showed a negative slope in the
      potential range from -45 to -5 mv which corresponded to the negative slope for
      the peak sodium current relation vs. membrane potential which suggested long
      duration sodium currents. Using sodium-free sea water externally, sodium currents
      were separated from total currents and these persisted for longer times than
      normal. This result suggested that internal cesium ion delays the sodium
      conductance turnoff. The separated nonsodium currents showed an abnormal
      rectification as compared with those predicted by the independence principle,
      such that while potassium permeability appeared normal at the resting potential,
      its value decreased progressively with increasing depolarization.

PMID- 11526830
TI  - Energetics of coupled active transport of sodium and chloride.
AB  - A Clark electrode was used to measure oxygen consumption by the gall bladder, in
      which there is a direct and one-to-one linkage between active Na and active Cl
      transport. O2 uptake was reversibly depressed when Cl in the mucosal bathing
      solution was replaced by a poorly transported anion, such as sulfate. This effect
      of Cl was abolished by ouabain or in Na-free solutions. When the anion was
      chloride, treatment with ouabain or replacement of Na by a poorly transported
      cation depressed QO2 more than did replacement of Cl. However, ouabain or removal
      of Na also depressed QO2 in Na2SO4 solutions, in which salt transport is minimal.
      It is concluded that oxygen uptake in the gall bladder consists of three
      fractions: 9% requires both Na and Cl, is inhibited by ouabain, and is linked to
      the NaCl pump; 36% requires Na but not Cl, is inhibited by ouabain, and possibly
      is linked to the cellular K uptake mechanism; and 55% represents basal uptake. If
      the extra oxygen uptake observed during transport supplies all the energy for
      transport, then 25 Na + 25 Cl ions are transported actively per O2 consumed;
      i.e., twice as many ions as in epithelia which transport only Na actively. This
      extra uptake is more than sufficient to supply the energy for overcoming internal
      membrane resistance under the experimental conditions used.

PMID- 11526831
TI  - Oxygen consumption rate of tissue measured by a micropolarographic method.
AB  - A new method for measuring the oxygen consumption rate of a sheet of homogeneous
      tissue is described. The method measures, by a Clark-type oxygen electrode
      without a membrane, the time for the tissue to consume all its dissolved oxygen.
      The electrode is applied to one surface of the tissue sheet and the other surface
      is sealed from the atmosphere by a cover slip. The consumption is calculated from
      an estimate of the oxygen dissolved in the tissue at the moment it is covered and
      the time for the oxygen tension at one surface to fall to zero. The data also
      yield the oxygen diffusion coefficient in the oxygen-consuming tissue.

PMID- 11526832
TI  - Stimulation of the salt receptor of the blowfly. I. NaCl.
AB  - Application of NaCl solutions to the tip of a labellar sensillum of the blowfly
      elicited a repetitive neural response from the salt receptor. The response was
      examined with respect to reproducibility and adaptation. A threshold was observed
      for tests with dilute solutions. Above this, the response increased linearly with
      the logarithm of the molarity. The response was not significantly affected by the
      pH of stimulating solutions, buffered or not, between 3 and 10. Beyond this
      range, it was reversibly inhibited until, at greater extremes of pH, atypical
      stimulation independent of the presence of salt was seen. Receptor sensitivity
      increased with fly age. The results presented here may be due to effects at sites
      in the sensillum other than the receptor membrane.

PMID- 11526833
TI  - Stimulation of the salt receptor of the blowfly. II. Temperature.
AB  - The response of the salt receptor of the blowfly increased with increasing
      ambient temperature. At constant ambient temperature, the response increased as
      the relative humidity was raised. At low relative humidity, the temperature of
      the stimulating solution near its air interface was markedly below ambient
      temperature, due to evaporation. Warming and cooling the tip of the sensillum
      while recording from its side respectively raised and lowered the frequency of
      "spontaneous" action potentials of the receptor. The results indicate that the
      response of the salt receptor is dependent on the temperature of the stimulus.
      The Q10 is probably several times greater than one.

PMID- 11526834
TI  - Stimulation of the salt receptor of the blowfly. III. The alkali halides.
AB  - Application of solutions of each of the alkali halides to the tip of a labellar
      sensillum of the blowfly elicited a repetitive neural discharge from the salt
      receptor. The records were qualitatively similar to those for NaCl. For each of
      the alkali chlorides and sodium halides, the shapes of the curves of the response
      of the salt receptor as a function of concentration were similar to that for
      NaCl. The alkali halides exhibited a regular pattern of relative stimulating
      effectiveness for the salt receptor. The effectiveness of the anions increased
      monotonically with atomic number. The effectiveness of the cations was greatest
      for potassium and declined as the atomic number was increased or decreased. This
      hierarchy for stimulating effectiveness was maintained at all tested molarities.
      The response to a mixture of two salts appeared to be an average of those to the
      single salts at concentrations equal to the total concentration of the mixture.
      Cross-adaptation was observed between the alkali halides. The results indicate
      that an explanation of stimulation of the salt receptor must apply to all the
      salts tested and that both the anion and the cation affect a salt's stimulating
      effectiveness.

PMID- 11526835
TI  - Increased mutation rate of E. coli K12 lambda cultures maintained in continuous
      logarithmic growth.
AB  - Continuous logarithmic growth of E. coli K12 lambda in an automatic culture cell
      resulted in marked increases in the proportion of several mutants. The P1 phage
      resistant cells increased 10 to 3000 times, the T2 phage-resistant cells 1 to
      1000 times, the neomycin-resistant cells 1 to 10 times, and the virus-producing
      cells 30 to 70 times. No change occurred in the penicillin-resistant cells.
      Calculation of the growth curves and direct determination of the mutation rates
      by the null fraction method showed that the increases in the proportion of
      mutants were due to increases in the mutation rates.

PMID- 11526836
TI  - Cytodifferentiation and membrane transport properties in LK sheep red cells.
AB  - Young cells produced in LK sheep during rapid hematopoiesis after massive
      hemorrhage contain more K than the cells which are normally released into the
      circulation. The K content in these new cells falls to that characteristic of
      mature LK cells after a few days in the circulation. K transport properties in
      young and old cells before and after massive bleeding were studied. Young and old
      cells were separated by means of a density gradient centrifugation technique.
      Evidence showing that younger cells are found in the lower density fractions is
      presented. Active transport of K in the lightest fraction as measured by
      strophanthidin-sensitive influx was four to five times greater in red cells drawn
      6 days after massive bleeding while the K leak as measured by strophanthidin
      insensitive influx was only slightly larger. No change after bleeding was
      observed in older cells which had been present in the circulation prior to the
      hemorrhage. It is concluded that the high K content of young cells produced in LK
      sheep after bleeding is due to temporary retention of membrane K transport
      properties characteristic of HK cells. Thus, genetically determined modification
      of membrane transport properties has been shown to occur in nondividing
      circulating red cells.

PMID- 11526837
TI  - Exchange diffusion effect and euryhalinity in teleosts.
AB  - The sea water (SW)-adapted euryhaline Platichthys flesus, and the marine Serranus
      exchange about 50% of their internal sodium with the external sodium per hour.
      This rate of exchange decreases with decreasing salinity of the adaptation
      medium. When the flounder is transferred from SW to FW an instantaneous 90%
      reduction of the Na and Cl outflux is observed. About 30 min later a second,
      progressive, reduction occurs. The outflux reductions appear to result from two
      types of regulatory mechanisms reducing gill permeability and preventing
      excessive salt loss. The first reduction corresponds to independent "Na- and Cl
      free effects" as shown by transfers to artificial media containing either Na or
      Cl with an impermeant co-ion. The pattern of simultaneous rapid variations of Na
      influx and outflux for a range of salinity changes in flounder adapted to SW, 1/2
      SW, or 1/4 SW has been studied. The data are compatible with the hypothesis of an
      exchange diffusion mechanism characterized by a coupling of both unidirectional
      fluxes. The affinity of the exchange diffusion carrier for sodium has been
      measured (Km approximately equal to 400 mM). The delayed reduction would result
      from a progressive diminution of the quantity of carrier available but without
      modification of its affinity for sodium. When the stenohaline marine perch is
      transferred from SW to FW, a 40% reduction of the outflux is observed. But it is
      not the result of an exchange diffusion effect as it is related to the external
      osmolarity change and not to the NaCl concentration change. Furthermore no
      delayed reduction is observed after transfer into FW. This transfer is
      accompanied by a heavy loss of electrolytes resulting in a rapid decline of the
      plasma electrolyte level and death. A comparative survey of the relative
      importance of these regulatory mechanisms has been made.

PMID- 11526839
TI  - Effect of ions on the efflux of acetylcholine from peripheral nerve.
AB  - The nerves from the walking leg of lobster released acetylcholine (ACh) even when
      the ends were tied off, although this release was significantly increased when
      the nerve endings were not tied. The resting nerves were kept in sea water
      containing physostigmine. In absence of physostigmine no ACh was found in the
      surrounding fluid. Removal of Ca from the sea water reduced the release of ACh,
      while increased concentrations of Ca had no significant effect. Removal of Mg++
      or increased Mg++ concentrations in the presence of normal Ca++ concentrations
      increased the release of ACh. Increased K+ concentrations had a stimulating
      action on the efflux of ACh. Increased or reduced Na+ concentrations had only
      slight effects on the release of ACh in resting lobster nerve. During the 4 hr
      observation period the excised nerves were still able to synthesize ACh. The
      choline acetylase activity was stimulated by increased concentrations of Mg++ and
      K+. The effects of ions on the release of ACh are similar to those reported at
      the junction.

PMID- 11526838
TI  - Osmometrically determined characteristics of the cell membrane of squid and
      lobster giant axons.
AB  - Lobster and squid giant nerve fibers respond differently when subjected to
      osmotic challenges. The axons proper, as distinct from the total (fiber) complex
      formed by the axon and connective sheath, both behave as "fast" osmometers for
      changes in the concentration of NaCl, but the maximum degree of swelling in
      hyposmotic media is by about 60% in lobster and only by 20% in squid. The
      relative volume intercepts of the van't Hoff relation are about 0.2 for lobster
      and 0.4 for squid. The sheaths of both axons undergo only small, apparently
      passive changes in volume. Lobster axons are permeable to Cl, but squid axons are
      impermeable to this anion. Lobster axons are also permeable to glycerol. The
      implications of the data as to the nature of volume regulation of cells are
      discussed.

PMID- 11526840
TI  - Ionic conductance changes in lobster axon membrane when lanthanum is substituted
      for calcium.
AB  - The trivalent rare earth lanthanum was substituted for calcium in the sea water
      bathing the exterior of an "artificial node" of a lobster axon in a sucrose gap.
      It caused a progressive rise in threshold, and a decrease in the height of the
      action potential as well as in its rates of rise and fall. Prolonged application
      produced an excitation block. Voltage-clamp studies of the ionic currents showed
      that the time courses of the ionic conductance changes for both sodium and
      potassium were increased. Concurrently, the potentials at which the conductance
      increases occurred were shifted to more positive inside values for the La+++ sea
      water. These effects resemble changes resulting from a high external calcium
      concentration. Over and above this, La+++ also causes a marked reduction in the
      maximum amount of conductance increase following a depolarizing potential step.
      Membrane action potentials similar to those observed experimentally in the La+++
      solution have been computed with appropriate parameter changes in the Hodgkin
      Huxley equations.

PMID- 11526842
TI  - Time course of TEA(+)-induced anomalous rectification in squid giant axons.
AB  - Changes in the voltage clamp currents of squid giant axons wrought by low
      axoplasmic TEA+ (tetraethylammonium chloride) concentrations (0.3 mM and above)
      are described. They are: (a) For positive steps from the resting potential in sea
      water, the K+ current increases, decreases, then increases, instead of increasing
      monotonically. (b) For positive steps from the resting potential in 440 mM
      external K+, the current has an exponentially decaying component, whose decay
      rate increases with axoplasmic [TEA+]. The control currents increase
      monotonically. (c) For negative steps from the resting potential in 440 mM
      external K+, the current record has a peak followed by a decay that is slow
      relative to the control. The control record decreases monotonically.
      Qualitatively these findings can be described by a simple kinetic model, from
      which, with one assumption, it is possible to calculate the rate at which K+ ions
      move through the K+ channels. An interesting conclusion from (c) is that the
      channels cannot be closed by the normal voltage-sensitive mechanism (described by
      Hodgkin and Huxley) until they are free of TEA+.

PMID- 11526841
TI  - Anion permeability of the olfactory receptive membrane.
AB  - The ionic mechanism of the electropositive olfactory receptor potential was
      studied in the bullfrog and the swamp frog. The positive receptor potential
      strikingly decreased in amplitude in chloride-free solution. When the olfactory
      epithelium was immersed in high-KCl-Ringer's solution and then in Cl-free, high-K
      solution, the polarity of the positive potential could be reversed. This is
      supposed to be due to the exit of the increased internal chloride ion. From the
      above two experiments it is concluded that the positive olfactory receptor
      potential depends primarily upon the influx of the chloride ion through the
      olfactory receptive membrane. Some contribution by potassium and possibly other
      ions may occur. The ability of other anions to substitute for chloride was
      examined. It was found that only Br-, F-, and HCO2- could penetrate the olfactory
      receptive membrane. The sieve hypothesis in the inhibitory post-synaptic membrane
      (Coombs, Eccles, and Fatt, 1955) is not applicable to the olfactory receptive
      membrane on the basis of the size of hydrated ions, but it may be applicable on
      the basis of the sizes of naked ions.

PMID- 11526844
TI  - Mach band type lateral inhibition in different sense organs.
AB  - Experiments were done on the skin with shearing forces, vibrations, and heat
      stimuli and on the tongue with taste stimuli to show that the well known Mach
      bands are not exclusively a visual phenomenon. On the contrary, it is not
      difficult to produce areas of a decreased sensation magnitude corresponding to
      the dark Mach bands in vision. It is shown on a geometrical model of nervous
      interaction that the appearance of Mach bands for certain patterns of stimulus
      distribution is correlated with nervous inhibition surrounding the area of
      sensation. This corroborates the earlier finding that surrounding every area
      transmitting sensation there is an area simultaneously transmitting inhibition.

PMID- 11526843
TI  - The effect of high sodium concentration on the action potential of the skate
      heart.
AB  - It already has been well documented that the maximum rate of depolarization and
      amplitude of action potentials are directly dependent on [Na+]o in the vertebrate
      myocardium. Almost all studies have been carried out at low sodium concentration
      ranges by substituting NaCl for other substances. Action potentials should be
      demonstrable in higher sodium concentrations, but cells are inevitably damaged by
      osmotic changes. The blood of elasmobranchs is nearly isosmotic with sea water,
      but NaCl accounts for 54.5% of the osmotic pressure and 38.7% of it is maintained
      by urea molecules. Utilizing this special situation in elasmobranchs, the effect
      of high sodium concentration was studied up to 170% of normal sodium
      concentration, while still retaining isosmotic condition. The rate of
      depolarization, amplitude, and duration of the myocardial action potential all
      increased in direct proportion to [Na+]o, and no depressant effect on
      transmembrane action potentials was observed in solutions of high sodium
      concentration. With regard to depolarization rate, the regression curve fitted by
      the least squares method passed through zero within two standard errors. At high
      sodium levels, the overshoot changed as expected theoretically, but at lower
      ranges it deviated from the theoretical values. [Na+]i and [K+]i in this tissue
      have been determined, and these data are explained on the basis of the Na theory.

PMID- 11526845
TI  - Tracer and nontracer potassium fluxes in squid giant axons and the effects of
      changes in external potassium concentration and membrane potential.
AB  - The efflux of labeled and unlabeled potassium ions from the squid giant axon has
      been measured under a variety of experimental conditions. Axons soaked in sea
      water containing 42K ions lost radioactivity when placed in inactive sea water
      according to kinetics which indicate the presence of at least two cellular
      compartments. A rapidly equilibrating superficial compartment, probably the
      Schwann cell, was observed to elevate the specific activity of 42K lost from such
      axons to K-free sea water for a period of hours. The extra radioactive potassium
      loss from such axons during stimulation, however, was shown to have a specific
      activity identical within error to that measured in the axoplasm at the end of
      the experiment. The same was shown for the extra potassium loss occurring during
      passage of a steady depolarizing current. Axons placed in sea water with an
      elevated potassium ion concentration (50 mM) showed an increased potassium efflux
      that was in general agreement with the accompanying increase in membrane
      conductance. The efflux of potassium ions observed in 50 mM K sea water at
      different membrane potentials did not support the theory that the potassium
      fluxes obey the independence principle.

PMID- 11526846
TI  - Enhanced permeability to sugar associated with muscle contraction. Studies of the
      role of Ca++.
AB  - When contractures were induced in isolated frog sartorius muscles with 4 mM
      caffeine, there was an increase in permeability of the muscle cells to 3
      methylglucose. This observation suggests that the changes in permeability to
      sugar that are known to occur in electrically stimulated muscles may not be
      intimately related to the depolarization phase of the tissue response.
      Contractures that were elicited by exposing the muscles to a high concentration
      of K+ were also associated with an increased permeability to sugar. As the
      concentration of 45Ca in the medium was raised, more 45Ca entered the muscles
      during potassium contractures, and the contractures lasted longer, in agreement
      with the observations of other investigators. There was also a greater change in
      permeability to sugar when potassium contractures were elicited in the presence
      of higher concentrations of Ca++. The possibility that the enhanced permeability
      to sugar may be related to changes in the intracellular concentration of Ca++ is
      discussed.

PMID- 11526847
TI  - Light metabolism and chloroplast structure in chlorophyll-deficient tobacco
      mutants.
AB  - In tobacco mutants which contain 1/8 to 1/30 of the normal chlorophyll content
      per leaf area the content of yellow pigments (carotenoids) is also diminished but
      less in proportion to the chlorophyll content. The pale yellow-green mutant grows
      and matures provided that light intensity and temperature make up for the
      chlorophyll deficiency. In most green plants and algae light saturation of
      photosynthesis is reached between 5000 and 12,000 ergs/sec.cm2. The mutants
      continue to give higher photosynthetic rates until the incident intensity reaches
      50,000 ergs/sec.cm2. While often unable to compensate their respiration at
      intensities at which the normal green plant approaches saturation, the pale
      yellow-green leaves are able to provide the mutant plant with two to three times
      the absolute amount of carbon dioxide assimilation per hour and leaf area at
      50,000 ergs/sec.cm2 and 20 degrees to 25 degrees C. These observations are valid
      for red light lambda > 600 m mu. In blue light lambda < 575 m mu (below
      saturation levels) the mutants separate into two classes, one in which absorption
      by some carotenoid enhances the photosynthetic rate and the other in which the
      absorbing pigments are inactive and therefore depress the rate strongly. The
      unusual kinetics of photosynthesis in these chlorophyll-deficient tobacco mutants
      is reflected in the structure of their chloroplasts which we found to be of a
      kind thus far not described for healthy, normally growing, higher plants.

PMID- 11526848
TI  - Surface density of calcium ions and calcium spikes in the barnacle muscle fiber
      membrane.
AB  - The effects of various divalent cations in the external solution upon the Ca
      spike of the barnacle muscle fiber membrane were studied using intracellular
      recording and polarizing techniques. Analysis of the maximum rate of rise of the
      spike potential indicates that different species of divalent cations bind the
      same membrane sites competitively with different dissociation constants. The
      overshoot of the spike potential is determined by the density of Ca (Sr) ions in
      the membrane sites while the threshold membrane potential for spike initiation
      depends on the total density of divalent cations. The order of binding among
      different divalent and trivalent cations is the following: La+++, UO2++ > Zn++,
      Co++, Fe++ > Mn++ > Ni++ > Ca++ > Mg++, Sr++.

PMID- 11526849
TI  - The electrical and mechanical activity of the esophageal cell of Ascaris
      lumbricoides.
AB  - The esophagus of Ascaris is a syncytial muscle organ of tubular shape in which
      the myofibrils are arranged radially between the lumen and the external surface.
      A resting potential of almost 40 mv (cytoplasm negative) is maintained by the
      extracellular organic anions (volatile fatty acids) found in the perienteric
      fluid. Replacement of these anions by Cl- ions results in a large depolarization.
      The resting potential is also decreased when the external pH is lowered. The
      leading phase of the action potential with a positive overshoot of about 18 mv
      elicits contraction of the myofibrils, development of negative pressure within
      the lumen, and suction of liquid and food particles. The mechanical energy stored
      in the elastic components of the cell is released when the myofibrils relax, thus
      injecting the contents of the lumen into the intestine. A fast and synchronous
      relaxation is elicited by a regenerative membrane polarization, a negative spike
      with a peak value of up to 108 mv produced by an increase in the permeability of
      the membrane to K+ ions. Cells completely depolarized in "chloride" saline are
      still able to generate such large potassium spikes.

PMID- 11526850
TI  - Extracellular action potentials recorded from the interior of the giant
      esophageal cell of Ascaris.
AB  - Exploration of the cytoplasm of the giant esophageal cell of Ascaris with a
      recording microelectrode shows the existence of shallow spaces where the
      microelectrode tip becomes extracellular in spite of being in the interior of the
      cell. When the microelectrode penetrates into these spaces from the cytoplasm,
      the resting potential shifts to a different level or entirely disappears. At the
      same time the large intracellular spikes are replaced by small transients similar
      to extracellularly recorded action potentials. It is concluded that such spaces
      are in communication with the external solution, and separated from the cytoplasm
      by an electrically active membrane; i.e., able to generate action potentials.
      Measurement of the potential differences between the interior of the spaces and
      the external solution shows that although some are not polarized, many spaces
      have a resting potential of the same polarity as that of the cytoplasm. It is
      suggested that although they are of larger size these spaces may be equivalent to
      the tubular systems which in other muscle cells are known to be involved in the
      spread of excitation into the cytoplasm.

PMID- 11526851
TI  - The circadian rhythm in photosynthesis in Acetabularia in the presence of
      actinomycin D, puromycin, and chloramphenicol.
AB  - Anucleate Acetabularia crenulata shows a circadian rhythm in photosynthesis. In
      this study, an oxygen electrode was employed to measure this photosynthetic
      rhythm in the presence and absence of the inhibitors, actinomycin D,
      chloramphenicol, and puromycin. High concentrations of the inhibitors were used:
      actinomycin D, 20-40 micrograms ml-1; puromycin, 30 and 100 micrograms ml-1; and
      chloramphenicol, 250 micrograms ml-1. The effectiveness of these inhibitors on
      protein synthesis was also measured under the same conditions used for the
      determination of rhythmicity. In spite of large effects of all three inhibitors
      on the incorporation of 14C leucine, no effect on the period or the phase of the
      photosynthetic rhythm was observed. The higher concentration of puromycin and
      chloramphenicol produced toxic effects which were expressed as a reduction in the
      amount of photosynthesis, but rhythmicity was still apparent. After 3 or 4 days'
      exposure to actinomycin, Acetabularia became resistant to its effect. Recovery
      was also observed in the ability to incorporate leucine. The implications of
      these results for theories of the basic oscillator responsible for circadian
      rhythmicity are discussed.

PMID- 11526852
TI  - Active state in heart muscle. Its delayed onset and modification by inotropic
      agents.
AB  - The course of active state in heart muscle has been analyzed using a modified
      quick release method. The onset of maximum active state was found to be delayed,
      requiring 110-500 msec from time of stimulation, while the time to peak isometric
      tension required 250-650 msec. Further, the time from stimulation to peak tension
      was linearly related to the time required to establish maximum intensity of
      active state as well as to the duration of maximum active state. The duration of
      maximum active state was prolonged (90-220 msec), occupying most of the latter
      half of the rising phase of the isometric contraction. Norepinephrine (10(-5) M)
      shortened the latency from electrical stimulus to mechanical response,
      accelerated the onset of maximum active state, increased its intensity, decreased
      its duration, and accelerated its rate of decline. These changes were accompanied
      by an increase in the rate of tension development and the tension developed while
      the time from stimulation to peak isometric tension was abbreviated. Similar
      findings were shown for strophanthidin (1 microgram/ml) although lesser
      decrements in the duration of maximum active state and time to peak tension were
      found than with norepinephrine for similar increments in the maximum intensity of
      active state.

PMID- 11526853
TI  - The extracellular space of voluntary muscle tissues.
AB  - The volume occupied by the extracellular space has been investigated in six types
      of voluntary muscles: sartorius (frog), semitendinosus (frog), tibialis anticus
      longus (frog), iliofibularis (frog), rectus abdominis (frog), and diaphragm
      (rat). With the aid of four types of probe material, three of which are
      conventionally employed (inulin, sorbitol, sucrose) and one of which is newly
      introduced (poly-L-glutamate), and a different experimental method, we have
      demonstrated that the "true" extracellular space of frog sartorius,
      semitendinosus, tibialis anticus longus, and iliofibularis muscle and of rat
      diaphragm muscle is equal to, or probably less than, 8-9% (v/w) of the tissue.
      The frog rectus muscle shows a somewhat higher ceiling value of 14%.

PMID- 11526854
TI  - The transport of salt and water across isolated rat ileum. Evidence for at least
      two distinct pathways.
AB  - The flows of sodium, potassium, and chloride under electrical and chemical
      gradients and of salt and water in the presence of osmotic pressure gradients are
      described by phenomenological equations based on the thermodynamics of
      irreversible processes. The aim was to give the simplest possible description,
      that is to postulate the least number of active transport processes and the least
      number of separate pathways across the intestine. On this basis, the results were
      consistent with the following picture of the intestine: Two channels exist across
      this tissue, one allowing only passive transport of ions and the other only
      active. In the passive channel, the predominant resistance to ion flow is
      friction with the water in the channel. The electroosmotic flow indicates that
      the passive channel is lined with negative fixed charged groups having a surface
      charge density of 3000 esu cm-2. The values of the ion-water frictional
      coefficients, and the relationship between ionic concentrations and flows
      indicate that the passive channel is extracellular. The active channel behaves as
      two membranes in series, the first membrane being semipermeable but allowing
      active transport of sodium, and the second membrane being similar to the passive
      channel. Friction with the ions in the second "membrane" is the predominant
      resistance to water flow.

PMID- 11526855
TI  - Phenomenological description of active transport of salt and water.
AB  - The phenomenological definition of active transport by Kedem and the methods of
      Kedem and Katchalsky have been used to obtain practical equations describing
      active transport in the single salt and bi-ionic systems. Procedures were devised
      to evaluate the required set of 10 coefficients for the single salt case and 15
      for the bi-ionic. Three of these coefficients are unusual. They express the
      effects of active transport, i.e. of entrainment between metabolism and the
      conventional transport flows: active salt transport coefficient, a volume pump
      coefficient, and an electrogenicity coefficient. In the bi-ionic case a new
      passive coefficient, lambda, was used to express the linkage between the fluxes
      of the two salts. However, if primary active transport involves only one ion, for
      example in the bi-ionic case, 12 coefficients suffice and certain relations can
      be predicted between the practical coefficients. Particular types of primary
      active transport could be identified by this means. The relation of active
      transport to membrane electrogenesis was also examined and the flux ratio
      equation was rederived in terms of the practical coefficients. Applications to
      specific parallel and series membrane systems have been analyzed.

PMID- 11526856
TI  - Analysis of compound postsynaptic potentials in the central nervous system of the
      surf clam.
AB  - Compound postsynaptic potentials, comprising graded excitatory-inhibitory
      sequences, are the characteristic mode of response to afferent input exhibited by
      a population of cells in the visceroparietal ganglion of Spisula. Experimentally
      induced interaction between the phases of the response indicates that the
      observed sequential invasion represents differences in individual component
      latencies, rather than the physiological resultant of two separate processes
      having simultaneous onset but different rates of decay. Excitation is depressed
      by changes in membrane conductance throughout the duration of the inhibitory
      phase; moreover, since similar pathways from the periphery initiate both phases,
      excitatory events are limited to a duration roughly equal in length to the
      latency for the inhibition. Within this interval repetitive volleys can evoke
      summation of excitatory events. The inhibitory mechanism is temporally stable,
      however, and dominates the membrane during repetitive trains of volleys at 1 to
      100 per sec. Artificially generated increases in the membrane potential decrease
      the IPSP while increasing the amplitude of the EPSP. Thus, both phases of the
      compound response appear to result from events occurring at chemically
      transmitting synaptic loci. Evidence is presented that these events are driven
      via collaterals of the same afferent fibers. The behavioral role of these
      response sequences is uncertain. Analogies, in terms of some observed reflex
      activity in these clams, appear to exist but presently lack experimental
      verification.

PMID- 11526857
TI  - Drug spending keeps rising, but rate of increase slowing.

PMID- 11526858
TI  - Study demonstrates capitation's potential to hold down drug cost.

PMID- 11526859
TI  - Medicare HMOs, FFS plans provide equal care following heart attack.

PMID- 11526860
TI  - New York HMOs show mixed results compared with national averages.

PMID- 11526861
TI  - [Post-surgical and post-infectious meningoencephalic herniation in the middle
      ear].
AB  - Meningoencephalic hernia of the middle ear, due to the advent of antibiotics, the
      surgical microscope, and the new surgical techniques for the treatment of chronic
      otitis media, is an infrequent pathology in the presents days. The goal of this
      paper is to present four cases of meningoencephalic hernia of the middle ear,
      three of then postsurgical and the remaining of inflammatory origin. Diagnosis,
      treatment and complications are discussed. Meningoencephalic hernia of the middle
      ear is usually asymptomatic and diagnosis is accidental. Immediate surgical
      treatment is indicated in order to avoid the potential complications of this
      disease. Transmastoid approach has been used for three cases and a middle cranial
      fossa approach was used in the fourth patient.

PMID- 11526862
TI  - [Auditory training with wide-band white noise: effects on the verbal
      discrimination].
AB  - The auditory training with wide-band white noise is a methodology for the
      qualitative recovery of the hearing loss in people suffering from sensorineural
      hearing loss. It is based on the application of a wide-band white modified noise.
      In a prospective study, we have assessed the modifications of the verbal
      reception threshold URV), the maximum discrimination (Dmax), and the
      discrimination coefficient (Kd) in a sample of 48 patients, who have followed a
      program of 15 auditory training with wide-band white noise sessions. The average
      improvements of the verbal discrimination variables expressed in percentage are
      4.23% for the URV, a 9.04% for the kd, a 17.87% for the Dmax, and 4.32%, 10.05%,
      13.04% for the binaural URV, Kd and Dmax respectively. From our results, it can
      be deduced that the auditory training with wide-band white noise improves the
      verbal discrimination measures. Not only it allows to reach the verbal reception
      threshold at a lower intensity, but also it moves the discrimination line towards
      the left. Furthermore, it increases the maximum discrimination both in binaural
      measurements and in those which consider all the ears.

PMID- 11526863
TI  - [Treating benign paroxysmal positional vertigo with the canalith repositioning
      maneuver of Epley. Our experience].
AB  - Benign Paroxysmal Positional Vertigo (BPPV) is one of the most common peripheral
      vestibular disorders. Particle repositioning maneuvers are simple and effective
      treatments for patients with BPPV. This study included 37 consecutive cases of
      BPPV treated with the particle repositioning maneuver of Epley. 97% of patients
      improved and the maneuver was well tolerated. We conclude that Epley Maneuver is
      safe and effective in the treatment of BPPV.

PMID- 11526864
TI  - [Analysis of 2,500 squamous cell carcinoma of the head and neck].
AB  - The purpose of this paper is to define the prevalence of squamous cell carcinoma
      of the head and neck as seen at the ENT Department, Hospital de la Santa Creu i
      Sant Pau, Barcelona, Spain in the last years, studying 2500 cases. Relative
      frequencies at the various sites, age distribution, male to female ratios, TNM
      stage are reported. From the results we point out that laryngeal squamous cell
      carcinomas (1297 cases) were more than 50% of all tumors, followed by
      oropharygeal carcinomas, oral cavity carcinomas and hypopharyngeal carcinomas.
      The mean age was 61 years, and patients with nasopharyngeal carcinomas were the
      youngest. 92% of the patients were males, and the highest rate of males was seen
      in the larynx and hypopharynx (97% males). Only 9% of the patients were non
      smokers and 18% were not alcohol drinkers. Hypopharyngeal squamous cell
      carcinomas concentrated the highest rate of patients with severe toxic
      consumption. A significant proportion of earlier tumors was only seen in the
      larynx and oral cavity (54% and 41% Stages I-II, respectively). On the other
      hand, hypopharyngeal carcinoma, oropharyngeal carcinoma and nasopharyngeal
      carcinomas were mainly diagnosed in advanced stages.

PMID- 11526865
TI  - [Neoplastic invasion of laryngeal cartilage: diagnosis by computed tomography].
AB  - The diagnostic of the laryngeal cartilage neoplastic invasion plays an important
      role in the accurate staging of the laryngeal carcinoma and its treatment. To
      evaluate the accuracy of the CT diagnosing cartilage involvement, the present
      study is reported. 127 patients with carcinoma of the larynx and hipopharynx T3
      T4, surgical treated between 1993 and 1997 at Ciudad Sanitaria y Universitaria de
      Bellvitge, are retrospectively studied. TC presents an a accuracy of 78%, a
      specificity of 91% and a sensitivity of 54% in the diagnostic of laryngeal
      cartilage invasion of the laryngeal and hipopharyngeal carcinoma.

PMID- 11526866
TI  - [Cervical lymph node involvement in laryngeal carcinoma: a retrospective study of
      430 cases].
AB  - Cervical lymph node involvement in laryngeal tumors could be a market impact on
      the disease prognosis. We performed a retrospective study of 430 patients who
      underwent surgery to treat laryngeal carcinoma in our center over a 10-year
      period. The objective was to correlate clinical and pathological lymph node
      involvement with the site of origin and size of the tumor, the treatment and its
      impact on patient survival. We observed a significantly greater incidence of
      lymph node involvement in tumors originating from supraglottis, with a rate of
      occult lymph node metastases of 31%. Patients with lymphadenopathy that remained
      undetected in the absence of surgical treatment and those with nonmetastatic
      lymphadenopathy presented similar 5-year survival rates, 83% y 98% respectively.
      However, the 5-year survival decreased to 24% in the presence of metastatic lymph
      node involvement. These results support the proposal that treatment of laryngeal
      carcinoma should include the region of the cervical nodes as well.

PMID- 11526867
TI  - [Experience with the HME-Provox Stomafilter in laryngectomized patients].
AB  - Respiratory symptoms after total laryngectomy are both frequent and troublesome.
      Previous studies have demonstrated the positive effect of a heat and moisture
      exchanger (MHE) on the respiratory system in patients after total laryngectomy.
      In the present study we analyze the opinion of 40 total laryngectomized patients
      regarding the use of the MHE-Provox Stomafilter kit. Focus has been directed to
      speech function parameters and pulmonary symptoms. Benefits in phonatory
      parameters--intelligibility, fluency, pressure and telephone intelligibility,
      have been over 70%. Reduction in pulmonary symptoms--coughing, sputum production,
      forced expectoration, stoma cleaning--have also been significant. Our results
      support the use of MHE Provox Stomafilter for minimizing and preventing
      respiratory problems and increasing the quality of the voice through the
      tracheoesophageal puncture system.

PMID- 11526868
TI  - [Hypopharynx and larynx basaloid squamous carcinoma: our experience with 6
      cases].
AB  - INTRODUCTION: Basaloid squamous carcinoma (BSC) of the head and neck is an
      uncommon, recently described variant of epidermoid carcinoma. BSC appears
      biologically with a greater propensity to local aggressiveness and metastatic
      potential than the conventional type. OBJECTIVES: To determine the incidence of
      BSC of the larynx and hypopharynx in our area, and to evaluate its behavior and
      prognosis. PATIENTS & METHODS: 272 cases of squamous carcinoma of the larynx and
      hypopharynx were reviewed and 6 diagnosis of BSC were made, corresponding to 6
      tumors in 5 patients. Their clinical records were analyzed. An
      immunohistochemical study was performed, including antibodies against
      cytokeratins (CK 7, CK 8, CK 19, CK 20, CK 1, 10, 5, 14, y CK 10), epithelial
      markers (EMA, CEA, Ber-EP4), vimentin and three neuroendocrine markers: neuron
      specific enolase, chromogranin and synaptophisin. Bcl-2 expression was also
      investigated. RESULTS: Most tumors were supraglottic. 5 out of 6 tumors were
      clinically benign, without any metastases or recurrence after exclusive surgical
      resection and a follow-up ranging 42 to 142 months. We detected a trend toward a
      primitive pattern of keratin expression. All tumors were stained with EMA and CEA
      MoAbs, but we could not find Ber-EP4 nor endocrine markers staining in any of
      them. However, BCL-2 expression was widely found in 4 out of 5 tumors
      immunostained. CONCLUSION: It seems to be a progressive dedifferentiation of the
      basaloid cell component, probably a subpopulation with more primitive features
      responsible of the aggressiveness reported in the literature. However, the
      surprising good prognosis in most of our cases makes necessary more studies and
      wider series to confirm our data.

PMID- 11526869
TI  - [Prevalence of oral lichen planus and oral leukoplakia in 112 patients with oral
      squamous cell carcinoma].
AB  - OBJECTIVE: To study the association existing between precancerous conditions,
      like oral lichen planus and oral leukoplakia into 112 patients with oral squamous
      cell carcinoma (OSCC). MATERIALS AND METHODS: We applied a protocol to 112
      patients with OSCC in the "Servicio de Estomatologia del Hospital General
      Universitario de Valencia". We made two groups: 1. patients with precancerous
      lesions and oral carcinoma, 2. patients with OSCC and no precancerous lesions.
      RESULTS: The average age was 61.4 years, 85 of them being men and 27 women. The
      tongue and floor of the mouth were the most common locations. 33.6% of the
      tumours presented stage TNM I, most of them being histologically well
      differentiated and the 55.8% were ulcerated. We found differences between two
      groups of the patients regarding alcohol and tobacco habits, location, size and
      clinical stage and histological differentiation of the malignant lesions.

PMID- 11526870
TI  - [Forestier's syndrome. Report of two cases].
AB  - Diffuse idiopathic skeletal hyperostosis (DISH) with cervical involvement which
      cause dysphagia is a rare disease. The otolaryngologist usually can make its
      diagnostic with a barium swallowing esophagogram. Two patients with DISH are
      reported.

PMID- 11526871
TI  - [Leiomyosarcoma of the larynx. Based on one case].
AB  - Leiomyosarcoma is a malignant tumour of smooth muscle cells. Usually is found in
      the gastrointestinal and female genital tracts, but is extremely rare in the
      larynx. Diagnosis is based in immunohistochemical studies. From the related
      literature is concluded that this tumour has a very aggressive behavior, with a
      very bad prognosis in spite of a radical surgery. A case of glottic Laryngeal
      Leiomyosarcoma (LL) treated with partial surgery is presented, There isn't any
      evidence of recurrent or metastases after a two years follow-up.

PMID- 11526872
TI  - [Maxillary ameloblastoma: report of two cases].
AB  - The ameloblastomas are benign odontogenic tumors locally aggressive that between
      15-20% are located in the upper maxillary. The maxillary ameloblastomas have
      worse forecast than their mandibular homologous upon presenting greater index of
      postsurgery relapses and a greater percentage of malignancy. Their proximity to
      nasal cavity, orbit and skull base suppose a risk added by the probability of
      extension to these structures.

PMID- 11526873
TI  - [Salivary gland myoepithelioma].
AB  - Myoepithelioma is a rare salivary gland tumor (less than 1%) which are usually
      located in parotid gland and minor salivary glands. Histology and
      immunohistochemical features of this tumors are reviewed. We report 2 cases
      arising in parotid and hard palate.

PMID- 11526874
TI  - Osteopathic manipulative treatment and outcomes for pneumonia.

PMID- 11526875
TI  - Urolithiasis update: clinical experience with the Swiss LithoClast.
AB  - This article describes the authors' first experience using the EMS Swiss
      LithoClast pneumatic lithotriptor in the management of middle and distal ureteral
      calculi. Also presented is a review of the literature comparing different
      modalities of intracorporeal lithotripsy. A retrospective analysis was performed
      on 11 patients treated with the Swiss LithoClast using the Circon ACMI MR6 Rigid
      Mini-ureteroscope (7 patients with distal calculi and 4 patients with midureteral
      calculi). The lithotriptor successfully fragmented 91% of the calculi,
      independent of stone composition. Complete failure of fragmentation was only
      encountered in one patient, and this was secondary to the lithotriptor's inherent
      ballistic force causing retrograde passage of the calculus. One patient had
      postoperative radiographic evidence of stone fragments along the ureteral stent.
      There was no intraoperative morbidity or long-term complications encountered with
      use of the pneumatic lithotriptor. Additionally, patients' overall satisfaction
      was 91% with respect to the procedure itself and relief of preoperative pain. The
      only significant postoperative complaint was ureteral stent discomfort in one
      patient. The authors conclude that the EMS Swiss LithoClast pneumatic
      lithotriptor is a safe and effective tool in the management of middle and distal
      ureteral calculi. However, as noted with one patient, there is always a risk of
      stone push from the ballistic force of the lithotriptor.

PMID- 11526876
TI  - Manual medicine diversity: research pitfalls and the emerging medical paradigm.
AB  - Recent studies published in leading medical journals have concluded that
      chiropractic treatment is not particularly helpful for relieving asthma and
      migraine symptoms because even though study participants showed notable
      improvement in symptoms, those subjects who received sham manual medicine
      treatments also showed improvement. Yet the sham treatment received by control
      groups in these studies is reminiscent in many ways of traditional osteopathic
      manipulation. This seems to represent not only a failure to recognize the value
      of many manual medicine techniques but also an ignorance of the broad spectrum of
      manual medicine techniques used by various practitioners, from osteopathic
      physicians to chiropractors to physical therapists. Such blind spots compromise
      research methodology with regard to manual medicine studies, which could, in
      turn, diminish the role of manual medicine in clinical practice. Osteopathic
      manipulative treatment provides an excellent model for recognizing and
      integrating the full range of manual medicine techniques into research and
      clinical applications because of the wide range of techniques employed. The
      potential exists for these techniques to contribute much to medical research and
      clinical practice--provided that osteopathic physicians and other manual medicine
      practitioners work to alleviate ignorance about the efficacy of various forms of
      manipulation.

PMID- 11526877
TI  - Digoxin toxicity in a 26-year-old woman taking a herbal dietary supplement.
AB  - Herbal dietary supplements are often considered by patients to be safe and free
      from side effects. The case described here shows digoxin toxicity in a patient
      taking a dietary supplement not normally considered to contain digoxin. In
      addition to highlighting the risks of herbal supplements, this case also
      demonstrates the concept that digoxin equivalents are not picked up by the
      standard digoxin assay.

PMID- 11526878
TI  - Osteopathic philosophy and emergent treatment in acute respiratory failure.
AB  - Osteopathic manipulation has been used to treat a wide range of diseases in
      largely outpatient settings. The authors describe the emergent use of osteopathic
      manipulative treatment to improve respiratory mechanics in a critically ill
      patient with acute respiratory failure. High-velocity mobilization of cervical
      and thoracic dysfunctions resulted in a decreased work of breathing, improved
      arterial oxygenation, resolution of tachycardia, and an overall improvement in
      the patient's clinical condition.

PMID- 11526879
TI  - Anal duct carcinoma: report of case and a survey of the experience of the
      American Osteopathic College of Proctology.
AB  - Anal duct carcinoma, also known as anal gland carcinoma or adenocarcinoma of the
      anal canal, is an unusual anal cancer that accounts for approximately 0.1% of all
      gastrointestinal cancers. Delays in diagnosis most likely account for the poor
      prognosis associated with this cancer. Presenting symptoms often mimic those of
      more common benign anorectal pathologic processes. Multimodality treatment that
      includes surgery, chemotherapy, and radiation therapy is often recommended. The
      authors describe a typical case of anal duct carcinoma and its management. They
      also discuss the findings of a survey of the combined experience of members of
      the American Osteopathic College of Proctology and review the literature.

PMID- 11526880
TI  - Periodontal diseases in children and adolescents: 2. Management.
AB  - Many of the periodontal diseases affecting children and adolescents can be
      successfully managed in general dental practice. The decision to treat the young
      patient in the practice setting or to refer to a periodontal specialist will
      depend on the complexity of treatment, patient factors and the expertise of the
      practitioner. Treatment should be provided in three phases: the initial cause
      related phase is aimed at controlling microbial plaque; the corrective phase is
      intended to restore function and aesthetics; supportive periodontal therapy is
      aimed at preventing recurrence and progression of periodontal disease. Even in
      cases requiring specialist referral, the dental team in general practice has a
      key role in the initial and supportive phases of therapy.

PMID- 11526881
TI  - A pictorial essay of clinical innovations with posterior tooth-coloured
      restorations.
AB  - The application of multi-surfaced posterior tooth-coloured restorations is an
      exercise in risk tolerance when dentine occupies the bulk of the tooth substrate.
      Success with posterior tooth-coloured restorations is dependent on interfacial
      integrity. Although the literature is full of guidelines on producing
      aesthetically pleasing restorations, most practising clinicians appreciate that
      clinical success involves more than aesthetics: success is strongly dependent on
      operative competence. This article describes a number of innovative clinical
      techniques and discusses the probationary status of current adhesive options and
      the need for excellence in all phases of these demanding restorative sequences.

PMID- 11526882
TI  - Treatment planning for the problem patient: restorative, ethical, legal and
      psychological perspectives. Case 2: Jacqueline.
AB  - Jacqueline's is the second of a series of four articles that aims to look at some
      of the problems patients may present with when they visit their dentist. Each
      article starts with a brief scenario about the hypothetical patient and his/her
      clinical problems. As well as the clinical problem, each case also raises
      ethical, legal or psychological problems. All of these issues are discussed and
      possible management strategies and treatment options described.

PMID- 11526883
TI  - A review of technology and safety aspects of erbium lasers in dentistry.
AB  - This article reviews aspects of the probable mechanisms used by erbium dental
      lasers for cutting dentine and enamel, describes key issues of the risk of
      temperature elevation and speed of cutting relative to conventional techniques
      and looks at issues concerned with the safety of lasers.

PMID- 11526884
TI  - Treatment planning for the loss of first permanent molars.
AB  - During the mixed-dentition stage of dental development, dentists may encounter
      patients with first permanent molars considered to have a poor long-term
      prognosis. In this situation, extraction of the tooth and space closure or use of
      the extraction space for future orthodontic treatment should be considered. The
      aim of this article is to give guidelines about treatment planning for patients
      who have first molars with a poor prognosis during the mixed-dentition stage.

PMID- 11526885
TI  - Submerging deciduous molars--an extraction in time!
AB  - A case is presented of a 25-year-old man with a submerged lower second deciduous
      molar and an impacted lower second premolar. Treatment was complicated by the
      relationship of the teeth to the inferior dental nerve, which necessitated
      extensive bone removal and mental nerve transposition to remove the submerged and
      impacted teeth. Early recognition and treatment of the submerging tooth might
      have prevented the need for such extensive surgery and morbidity at a later date.

PMID- 11526886
TI  - Vocational training: the case scenario workshop.
AB  - This article describes the procedure for conducting a workshop for a vocational
      training group, using six clinical case scenarios harvested from the vocational
      training group's own experience. During the session, the main group (which
      includes trainers) breaks up into smaller groups to discuss the management of
      each case, then a spokesperson presents the management solutions back to the re
      assembled larger group: further interaction and discussion then takes place. This
      article discusses six typical case scenarios from a recent workshop. The case
      scenario workshop is an exciting way to encourage discussion and interaction with
      all parties involved.

PMID- 11526887
TI  - Evaluation of the 1-year clinical performance of dentin-bonded ceramic crowns and
      four case reports.
AB  - OBJECTIVE: Dentin-bonded crowns are a comparatively recent addition to the
      dentist's armamentarium. Although 1-year data cannot predict the long-term
      performance of restorations, it may be useful for new treatment modalities, given
      that it will describe early, catastrophic failures. In this study, the 1-year
      performance of 109 dentin-bonded crowns was assessed. METHOD AND MATERIALS: The
      crowns were placed in two locations (Glasgow, Scotland, and Belfast, Northern
      Ireland) for 27 patients. The principal reasons for crown placement were tooth
      substance loss, esthetic reasons, and tooth fracture. Minimal preparations were
      used. Ninety-eight crowns were available for review at 1 year. RESULTS: Ninety
      crowns were found to be intact, six had a crack visible on transillumination and
      two had fractured. No crowns had debonded. No secondary caries was noted. No
      unsatisfactory scores were recorded for marginal adaptation, adjacent gingival
      health, or color match. CONCLUSION: The dentin-bonded crowns placed during this
      study provided good overall performance at 1 year.

PMID- 11526888
TI  - Assessment of clinical preparations for single gold and ceramometal crowns.
AB  - OBJECTIVE: Single-crown preparations at a dental teaching hospital were compared
      with guidelines advocated in the dental literature. METHOD AND MATERIALS: Sixty
      three single complete gold crown and 151 single ceramometal crown preparations
      were evaluated. Impression silhouettes were measured for occlusal and axial wall
      tooth reductions, shoulder widths, internal shoulder angles, and axial wall
      convergence angles. Marginal designs, the presence of retention grooves and
      undercuts, and the types of cores present were also recorded. RESULTS: Cuspal
      reduction was generally inadequate for the ceramometal crowns, and central fossa
      reduction was insufficient for both complete gold crowns and ceramometal crowns.
      The facial shoulder widths were also generally underprepared for the ceramometal
      crowns. Axial wall convergence angles for both complete gold crowns and
      ceramometal crowns were generally much greater than recommended. Large
      faciolingual convergence angles for anterior ceramometal crowns were associated
      with the absence of cingulum walls. Few preparations had retention grooves or
      undercut areas. CONCLUSION: Although strict guidelines for tooth preparations for
      complete crowns are available and well known to dentists, the preparations in
      this study did not always conform to these recommendations.

PMID- 11526890
TI  - Unusual maxillary second premolar morphology: a case report.
AB  - This case report presents the relatively uncommon occurrence of a maxillary
      second premolar with 3 root canals. The possibility of additional root canals
      should be considered even in teeth with a low frequency of abnormal root canal
      anatomy. Sound knowledge of root canal anatomy, critical interpretation of
      radiographs, and high-magnification examination are essential elements of success
      in complicated root canal therapy.

PMID- 11526889
TI  - Pulp-dentin biology in restorative dentistry. Part 3: Pulpal inflammation and its
      sequelae.
AB  - Physiologic and histopathologic experimental studies over the last 30 to 40 years
      have demonstrated that the healing of the dental pulp is comparable to that of
      connective tissue elsewhere, despite its location in the low-compliance pulp
      chamber. The greatest difficulty from a clinical point of view is to assess
      cellular changes and vitality of the pulp. If it is vital, the potential for
      repair is present, especially in young individuals.

PMID- 11526891
TI  - Early periodical literature of dental radiology.
AB  - Examination of the early literature of dental radiology reveals that dental
      scientists of the time were eager to experiment with the new technology but were
      unaware of the dangers associated with radiation.

PMID- 11526892
TI  - Pathologic changes in the pericoronal tissues of unerupted third molars.
AB  - OBJECTIVE: The purpose of this study was to determine whether the incidence of
      pathologic conditions affecting the pericoronal tissue of unerupted third molars
      justifies their routine removal. METHOD AND MATERIALS: The pericoronal tissue
      associated with completely unerupted third molars was submitted for histologic
      examination after surgical tooth removal was performed in 37 males and 55
      females, aged 13 to 63 years. The 104 unerupted third molars comprised 68
      mandibular third molars (65.38%) and 36 maxillary third molars (34.62%). RESULTS:
      The incidence of normal tissue of a dental follicle was 41.35%, and the incidence
      of pathologic tissue was 58.65% (dentigerous cyst, 50.96%; chronic nonspecific
      inflammatory tissue, 4.81%; odontogenic keratocyst, 1.92%; ameloblastoma, 0.96%).
      The incidence of pathologic conditions was higher than that of normal conditions
      in all third molar positions. In younger patients, normal tissue was more
      commonly found, but in patients older than 20 years, the incidence of pathologic
      tissue was higher than the incidence of normal tissue. CONCLUSION: Unerupted
      third molars should be removed before pathologic changes can occur in their
      pericoronal tissues. This justifies routine removal of unerupted third molars
      from patients older than 20 years.

PMID- 11526893
TI  - Premolar development in Greek children with cleft lip and palate.
AB  - OBJECTIVE: The purpose of this investigation was to study the development of the
      premolars in a sample of Greek children with cleft lip and palate. METHOD AND
      MATERIALS: The study material consisted of panoramic radiographs of 34
      individuals (22 boys and 12 girls) with cleft lip with or without cleft palate.
      The boys ranged from 9.0 to 14.0 years of age and the girls ranged from 8.0 to
      14.5 years of age. The mean age was 11.3 years. Each panoramic radiograph was
      matched with a corresponding one of an unaffected individual of the same sex and
      chronologic age (+/- 3 months). The panoramic radiographs were used to categorize
      the stages of tooth development according to the 10 stages of mineralization
      described by Nolla. The assessment was repeated by a second observer. RESULTS:
      Individuals with clefts exhibited a statistically significant delay of formation
      and mineralization of the maxillary right and left second premolars and the
      mandibular right second premolar in comparison to individuals without clefts. In
      the cleft group, there was no statistically significant difference between boys
      and girls in premolar development. No asymmetric development of contralateral
      premolar teeth was observed in individuals with cleft lip and palate. CONCLUSION:
      Although the exact biologic explanation remains to be found, the formation of
      premolars is delayed in children with cleft lip and palate.

PMID- 11526894
TI  - Anticariogenic effects of black tea (Camellia sinensis) in caries prone-rats.
AB  - OBJECTIVE: Black tea (Camellia sinensis) may have anticariogenic properties. The
      present study was designed to determine whether consumption of black tea
      influences cariogenesis in young, caries-prone rats. METHOD AND MATERIALS:
      Eighteen-day-old Sprague-Dawley rats (n = 24; eight per group) fed a cariogenic
      diet (MIT 200) were randomly assigned to three groups to receive deionized,
      distilled fluoride-free water, tea, or fluoridated water (25 ppm), ad libitum,
      for 14 days. In addition, an initial control group of rats was studied at 20 days
      of age. Teeth were stained with silver nitrate to detect caries and cut
      mesiodistally. First and second molars were assessed for caries. RESULTS: The
      initial control group had negligible caries. Caries-prone rats consuming fluoride
      free water had significantly more caries lesions (6.75) than did the tea (3.12)
      and the fluoridated water (0.85) groups. CONCLUSION: Consumption of black tea for
      2 weeks attenuated development and progression of caries in caries-prone young
      rats.

PMID- 11526895
TI  - Camille B. Capdeboscq, Jr: the good teacher.

PMID- 11526896
TI  - Focal epithelial hyperplasia (Heck's disease).

PMID- 11526897
TI  - Mississippi's highways are die-ways.

PMID- 11526898
TI  - Healthcare community responds to lawsuit abuse public rallies for tort reform.

PMID- 11526899
TI  - Pursuant to the Board's recommendation....

PMID- 11526900
TI  - [Distribution and correlation of uric acid with classic cardiovascular risk
      factors in an adult population in Campania. VIP project data].
AB  - BACKGROUND: The aim of this study was to correlate uric acid levels with the
      classic cardiovascular risk factors in an adult population in Campania. METHODS:
      The following parameters were assessed in the study population (600 men and 600
      women) aged between 25-74 years old, subdivided into 5 age groups (25-34, 35-44,
      45-54, 55-64, 65-74): ECG, arterial pressure and body mass index (obtained by
      dividing weight in kg by height in metres squared). A blood sample was also taken
      to evaluate uric and other biochemical variables including: total cholesterol,
      HDL, L DI, glycemia, triglycerides, red and white blood cells, C3, fibrinogen,
      platelets and insulin serum levels. RESULTS: The results confirmed the positive
      correlation between uric acid and red and white blood cells in males, and between
      uric and the following variables in females: cholesterol, C3, LDL, systolic blood
      pressure, diastolic blood pressure, triglycerides, white blood cells, BMI and
      fibrinogen. When the correlation was performed in the entire population, uric
      acid correlated with triglycerides and red and white blood cells. Multivariate
      analysis for the entire population showed a strong correlation between uric acid,
      triglycerides and white blood cells. CONCLUSIONS: This study confirms the data
      reported in the literature and highlights the correlation between uric and the
      classic cardiovascular risk factors. This association is more evident in females.

PMID- 11526901
TI  - Updated guidelines now available. Revised guidelines for using antiretroviral
      agents in adults and adolescents are now available on the Internet.

PMID- 11526902
TI  - Vaccine enters human trials.

PMID- 11526903
TI  - Chlamydia screening recommendations.

PMID- 11526904
TI  - Vaccine passes another test.

PMID- 11526906
TI  - Accessing more molecular diversity than presently exists on earth.

PMID- 11526905
TI  - Self-assembled molecular structures as ultrasonically-responsive barrier
      membranes for pulsatile drug delivery.
AB  - Noninvasive ultrasound has been shown to increase the release rate on demand from
      drug delivery systems; however, such systems generally suffer from background
      drug leaching. To address this issue, a drug-containing polymeric monolith coated
      with a novel ultrasound-responsive coating was developed. A self-assembled
      molecular structure coating based on relatively impermeable, ordered methylene
      chains forms an ultrasound-activated on-off switch in controlling drug release on
      demand, while keeping the drug inside the polymer carrier in the absence of
      ultrasound. The orderly structure and molecular orientation of these C12 n-alkyl
      methylene chains on polymeric surfaces resemble self-assembled monolayers on
      gold. Their preparation and characterization have been published recently (Kwok
      et al. [Biomacromolecules 2000;1(1):139-148]). Ultrasound release studies showed
      that a copolymer of 2-hydroxyethyl methacrylate and ethylene glycol
      dimethacrylate (MW 400) coated with such an ultrasound-responsive membrane
      maintained sufficient insulin for multiple insulin delivery, compared with a
      substantial burst release during the first 2 h from uncoated samples. With
      appropriate surface coating coverage, the background leach rate can be precisely
      controlled. The biological activity of the insulin releasate was tested by
      assessing its ability to regulate [C14]-deoxyglucose uptake in 3T3-L1 adipocyte
      cells in a controlled cell culture environment. Uptake triggered by released
      insulin was comparable to that of the positive insulin control. The data
      demonstrate that the released insulin remains active even after the insulin had
      been exposed to matrix synthesis and the methylene chain coating process.

PMID- 11526907
TI  - 'Anticalins': a new class of engineered ligand-binding proteins with antibody
      like properties.
AB  - The development of soluble receptor proteins that recognise given target
      molecules--ranging from small chemical compounds to macromolecular structures at
      a cell surface, for example--is of ever increasing importance in the life
      sciences and biotechnology. For the past century this area of application was
      dominated by antibodies, which were traditionally generated via immunisation of
      animals but have recently also become available by means of protein engineering
      methods. The so-called 'anticalins' offer an alternative type of ligand-binding
      proteins, which has been constructed on the basis of lipocalins as a scaffold.
      The central element of this protein architecture is a beta-barrel structure of
      eight antiparallel strands, which supports four loops at its open end. These
      loops form the natural binding site of the lipocalins and can be reshaped in
      vitro by extensive amino acid replacement, thus creating novel binding
      specificities. The bilin-binding protein (BBP) was employed as a model system for
      the preparation of a random library with 16 selectively mutagenized residues.
      Using bacterial phagemid display and colony screening techniques, several
      lipocalin variants--termed anticalins--have been selected from this library,
      exhibiting binding activity for compounds like fluorescein or digoxigenin.
      Anticalins possess high affinity and specificity for their prescribed ligands as
      well as fast binding kinetics, so that their functional properties are similar to
      those of antibodies. Compared with them, they exhibit however several advantages,
      including a smaller size, composition of a single polypeptide chain, and a simple
      set of four hypervariable loops that can be easily manipulated at the genetic
      level. Apart from haptenic compounds as targets, anticalins should also be able
      to recognise macromolecular antigens, provided that the random library is
      accordingly designed. Hence, they should not only serve as valuable reagents for
      bioanalytical purposes, but may also have a potential in replacing antibodies for
      medical therapy.

PMID- 11526908
TI  - Single domain camel antibodies: current status.
AB  - The antigen-binding capacity of the paired variable domains of an antibody is
      well established. The observation that the isolated heavy chains of anti-hapten
      antibodies retain some antigen-binding capacity in the absence of light chains
      led to attempts to obtain an even smaller antigen-binding unit in a VH format.
      Unfortunately, the poor solubility, the reduced affinity for the antigen and the
      irreproducible outcome showed that additional protein engineering would be
      required to successfully generate single-domain antibody fragments. By
      serendipity, it was discovered that this engineering is already performed
      continuously in nature. Part of the humoral immune response of camels and llamas
      is based largely on heavy-chain antibodies where the light chain is totally
      absent. These unique antibody isotypes interact with the antigen by virtue of
      only one single variable domain, referred to as VHH. Despite the absence of the
      VH-VL combinatorial diversity, these heavy-chain antibodies exhibit a broad
      antigen-binding repertoire by enlarging their hypervariable regions. Methods are
      described to tap the VHH repertoire of an immunised dromedary or llama. These VHH
      libraries contain a high titre of intact antigen-specific binders that were
      matured in vivo. Synthetic libraries of a 'camelised' human VH, a mouse VH or a
      camelid VHH scaffold with a randomised CDR3 could constitute a valid alternative
      to immune libraries to retrieve useful single-domain antigen binders. The
      recombinant VHH that are selected from such libraries are well expressed, highly
      soluble in aqueous environments and very robust. Some in vivo matured VHH were
      also shown to be potent enzyme inhibitors, and the low complexity of the antigen
      binding site is an asset in the design of peptide mimetics. Because of their
      smaller size and the above properties, the VHH clearly offer added-value over
      conventional antibody fragments. They are expected to open perspectives as enzyme
      inhibitors and intrabodies, as modular building units for multivalent or
      multifunctional constructs, or as immuno-adsorbents and detection units in
      biosensors.

PMID- 11526909
TI  - In vivo recombination as a tool to generate molecular diversity in phage antibody
      libraries.
AB  - The creation of diversity in populations of polypeptides has become an important
      tool in the derivation of polypeptides with useful characteristics. This requires
      efficient methods to create diversity coupled with methods to select polypeptides
      with desired properties. In this review we describe the use of in vivo
      recombination as a powerful way to generate diversity. The novel principles for
      the recombination process and several applications of this process for the
      creation of phage antibody libraries are described. The advantage and
      disadvantages are discussed and possible future exploitation presented.

PMID- 11526910
TI  - Cosmix-plexing: a novel recombinatorial approach for evolutionary selection from
      combinatorial libraries.
AB  - The efficiency of existing combinatorial biological library methods has been
      moderate in terms of the success rates, the affinities of the ligands selected
      and the time and effort involved in trying to optimize the initial leads.
      Although mimicking natural evolution, existing strategies take little notice of
      the importance of recombination within a selected population to generate
      increased diversity. We present an overview of our recent progress which has
      resulted in the successful development of such a strategy, which we designate
      cosmix-plexing. We incorporate recombination as a central feature in obtaining
      high success rates and high affinities, even for short monomer peptides, in a
      very short time. The method uses type II restriction enzymes to re-assort small
      hypervariable DNA cassettes from an intermediate pre-selected population (e.g.
      from a phagemid display library), while maintaining the original open-reading
      frame. Since, in the naive library, each cassette contains all possible
      combinations of the polypeptide sequences it encodes, much longer regions can be
      optimized than was possible with methods which depend on a simple selection from
      the naive library. Short peptides can now be rapidly selected, which exhibit the
      same, or higher, specificity and affinity for a defined target molecule, than
      (say) an antibody or even the natural ligand.

PMID- 11526911
TI  - Retroperitoneoscopic nephrectomy for benign diseases of the kidney.

PMID- 11526912
TI  - [Mesenteric panniculitis].

PMID- 11526913
TI  - Laboratory personnel shortages.

PMID- 11526914
TI  - Tac2-N, an atypical C-type tandem C2 protein localized in the nucleus.

PMID- 11526915
TI  - In vitro antitumor activity of cerivastatin, a novel and potent HMG-CoA reductase
      inhibitor.

PMID- 11526916
TI  - Vectors of diseases. Hazards and risks for travellers: Part II.

PMID- 11526917
TI  - [Conduct problems in a sample of institutionalized minors with previous
      mistreatment].
AB  - PURPOSE: The present study tries to analyse the maltreatment effects and the
      expected relation, according to the reviewed literature, with behaviour problems
      in a sample of children in residential care in a protection centre in Seville
      county (Spain). METHOD: The sample was conformed by a group of maltreated
      subjects in a protection setting (n = 30) and two groups of equivalent comparison
      (n = 30 and n = 30). The first group was conformed by subjects living in a
      marginal area of Sevilla, similar to the origin setting of the study group, and
      the second group comes from a wealthy area of this city. The behaviour problems
      index CBC of Achenbach (1978; 1979; Achenbach & Edelbrock, 1983) was used.
      RESULTS: No significant differences between groups in the CBC total score was
      found. However, significant differences were found in the extemalising dimension
      and in the delinquency, somatic anxiety, somatic problems, and social withdrawal
      dimensions. Victims of corruption presented higher scores on the CBC total score,
      extemalising dimension, and delinquency. CONCLUSIONS: Young people, victims of
      child maltreatment and living in an institution, showed problems of withdrawal.
      Victims of corruption or emotional abuse presented more psychopathological
      problems.

PMID- 11526918
TI  - The putative collagen binding peptide hastens periodontal ligament cell
      attachment to bone replacement graft materials.
AB  - BACKGROUND: Bone replacement graft (BRG) materials are often used to treat
      periodontal defects, to promote cellular invasion, and to encourage bone
      regrowth. Periodontal ligament fibroblasts (PDLF) incorporate these materials and
      form the basis of the renewed connection between the existing and newly formed
      alveolar bone and the tooth surface. A peptide (P-15) that mimics the putative
      cell-binding domain of collagen has been reported to promote dermal fibroblast
      attachment and proliferation. METHODS: PDLF were quantitatively examined for
      their ability to adhere to a variety of BRG materials fluorometrically. In
      addition, scanning electron microscopy was used to examine the changes in
      morphology exhibited by these cells as they attached and spread on several BRG
      materials. Finally, BRG materials containing the P-15 peptide were quantitatively
      examined for their ability to promote PDLF attachment and proliferation. RESULTS:
      Freeze-dried allograft bone supports greater PDLF attachment than does several
      xenograft and alloplastic anorganic bone replacement materials. An anorganic BRG
      material containing the P-15 peptide promoted more rapid cell attachment and
      spreading than a similar anorganic BRG material lacking this peptide. Finally,
      none of the BRG materials examined promoted PDLF proliferation. CONCLUSIONS: Our
      data indicate that the addition of the P-15 peptide increases the rapidity of
      PDLF attachment to xenogeneic bone replacement materials. This increase in the
      rate of attachment may have clinical significance in the context of the dynamic
      regulation of cell attachment during periodontal regeneration. However, this
      peptide does not promote an increase in stable cell attachment or proliferation
      in vitro.

PMID- 11526919
TI  - Lest we forget.

PMID- 11526920
TI  - Hydroxyethylstarch as a risk factor for acute renal failure in severe sepsis.

PMID- 11526921
TI  - Hydroxyethylstarch as a risk factor for acute renal failure in severe sepsis.

PMID- 11526922
TI  - Hydroxyethylstarch as a risk factor for acute renal failure in severe sepsis.

PMID- 11526923
TI  - Iodine intake in pregnancy.

PMID- 11526924
TI  - History of torture.

PMID- 11526925
TI  - History of torture.

PMID- 11526926
TI  - Frequency of esp in Enterococcus faecium isolates.

PMID- 11526927
TI  - Reporting of randomised controlled trials.

PMID- 11526928
TI  - Systemic lupus erythematosus.

PMID- 11526929
TI  - Systemic lupus erythematosus.

PMID- 11526930
TI  - Systemic lupus erythematosus.

PMID- 11526931
TI  - Systemic lupus erythematosus.

PMID- 11526932
TI  - Effects of multiple exposures to insecticide.

PMID- 11526933
TI  - Autotransplantation of ovarian tissue.

PMID- 11526934
TI  - Computerised application process for medical postgraduate study.

PMID- 11526935
TI  - Why are public-health policies ill made in japan?

PMID- 11526936
TI  - Implication in post-transfusion infection.

PMID- 11526937
TI  - A Smithsonian jewel: biological collections.

PMID- 11526938
TI  - Geneticists' views on embryonic stem cells.

PMID- 11526939
TI  - Parasitic plants major problem to food crops.

PMID- 11526940
TI  - The brain's susceptibility to amyloid plaques.

PMID- 11526941
TI  - Chiral selection when stirred, not shaken.

PMID- 11526942
TI  - Quinolones may mean shorter TB therapy.

PMID- 11526944
TI  - California sees rise in unsafe sex.

PMID- 11526943
TI  - TB therapy approach may delay AIDS.

PMID- 11526945
TI  - Fake AIDS drugs found.

PMID- 11526946
TI  - Infection rates on the rise.

PMID- 11526947
TI  - Chlamydia tests may be overused.

PMID- 11526948
TI  - Report From the 93rd Cardiovascular and   Renal Drugs Advisory Committee Meeting,
      August 9-10, 2001.

PMID- 11526949
TI  - Finding uncontrolled hypertensives.

PMID- 11526950
TI  - Lung-volume reduction surgery poses significant   mortality risks to the sickest
      patients.

PMID- 11526951
TI  - Immunoregulation of microglial functional properties.
AB  - Microglia are the resident tissue macrophages of the central nervous system (CNS)
      parenchyma and are key players in the initiation of an inflammatory response.
      Microglia rapidly transform from a resting to an activated morphology in response
      to a variety of disease states. However, they can also be the target of
      infections, as in the case of HIV. Many of the effector properties of microglia
      can be attributed to the array of substances they secrete in response to stimuli
      such as bacterial lipopolysaccharide, cytokines, and chemokines. The products of
      activated microglia include: cytokines (pro- and anti-inflammatory), chemokines,
      nitric oxide, superoxide radicals, and proteases. Furthermore, microglia have the
      ability to present antigen to T cells, migrate in response to chemotactic
      stimuli, and phagocytose cell debris. This report focuses on the immunomodulatory
      functions of microglia, with particular attention to chemokines, and highlights
      their pivotal role in the CNS.

PMID- 11526952
TI  - From theory to therapy: implications from an in vitro model of ramified
      microglia.
AB  - Microglia are the principal immune cells in the central nervous system (CNS),
      characterized by a highly specific morphology and unusual antigenic phenotype. An
      increasing number of studies have focused on the role of microglia in the
      pathogenesis of neurodegenerative diseases. To elucidate the function of
      microglial cells under several neuropathological conditions, we have studied and
      established a cell culture model that allows us to cultivate microglial cells in
      their inactive, resting (ramified) phenotype. In the first part of this work, we
      describe the interaction of microglia cells with their epithelial (astrocytic)
      microenvironment. The second part reviews experiments with microglia cell
      cultures to elucidate underlying signalling pathways and summarizes recent
      advances of our knowledge in microglial molecular pathways that may ultimately
      lead to neurodegeneration.

PMID- 11526953
TI  - Origin of microglia.
AB  - This paper reviews the various proposed hypotheses on the origin of microglia.
      The seminal study of del Rio-Hortega first stated that the cells were derived
      from the mesodermal pial cells that invaded the brain during embryonic
      development. Along with this was the description of precursor cells in the yolk
      sac in early development. Our results in the embryonic mouse brain have shown the
      occurrence of lectin-labelled precursor cells at the yolk sac that later appeared
      in the mesenchymal tissue associated with the neuroepithelium where they
      penetrated the nervous tissue to become the microglia. A second major view has
      held that microglia are of neuroectodermal origin; the cells either originate
      from glioblasts or the germinal matrix. Another school of thought is that
      microglia are derived from blood monocytes. In this connection, circulating
      monocytes enter the developing brain to assume the form as amoeboid microglia
      that subsequently evolve to become the ramified microglia. In traumatic brain
      lesions following an intravenous injection of colloidal carbon as a cytoplasmic
      marker for monocytes, it was found that carbon-labelled monocytes were the main
      source of brain macrophages, some of which transformed into microglia during the
      healing process. In conclusion, our results derived from the normal and altered
      brain development as well as from experimental lesions tend to favour the view of
      the monocytic nature of microglia. Recent studies by us also point to the
      possibility that some microglial cells may arise from the pial mesenchymal
      macrophages that appear to originate from the yolk sac precursors.

PMID- 11526954
TI  - Ion channels in cultured microglia.
AB  - Inward and, depending on activation state, outward potassium currents are the
      dominant ion channels in microglial cells in culture. During transition between
      resting and activated phases, there is also an upregulated expression of
      stretch/swelling-activated chloride currents. Pharmacological blockade of the
      specific potassium channels does not prevent the transition, whereas blockade of
      chloride channels does, suggesting that this current may be involved in phase
      changes. Interestingly, this chloride current is far less studied than the
      potassium currents with regard to the different microglial phases. One puzzling
      finding when studying microglial state is that despite changes in current
      densities and membrane oscillations during transition, there is no evidence of an
      accompanying change in membrane potential. In other cells of the immune system,
      membrane oscillations and alterations in membrane potential are correlated with
      transitions in cellular phases. This discrepancy in microglia may be a result of
      the fact that almost all ion channel and membrane potential studies in culture
      are undertaken with concomitant dialysis of cytoplasm with pipette solution.
      Further complicating matters is that the few studies that use microglia in situ,
      find fundamental differences in ion channel current patterns of "resting"
      microglia as well as different temporal changes to pathological events or
      stimuli.

PMID- 11526955
TI  - Establishment of microglial cell cultures derived from postmortem human adult
      brain tissue: immunophenotypical and functional characterization.
AB  - Cell cultures have become an integral part of the daily routine in most
      biological research laboratories. Because they are very dynamic and highly
      accessible, cell cultures permit direct experimental manipulations where cause
      effect relations can be more definitely assayed. We have developed cultures of
      microglial cells from rapid autopsies (range 3-10 hours) of nondemented elderly
      patients and Alzheimer's disease patients. Cultures were derived from the
      subcortical white matter, corpus callosum, and frontal, temporal, and occipital
      cortex. The adherent microglial cells were immunoreactive for CD68, CD45, CD11c,
      and major histocompatibility complex (MHC) class II markers, and were not
      immunoreactive for astrocyte or oligodendrocyte markers. In addition, some
      functional characteristics of the isolated microglial cells were also studied.
      Upon stimulation with lipopolysaccharide (LPS), microglial cells secreted pro-
      and antiinflammatory mediators, i.e., interleukin- (IL)-6, prostaglandin E2
      (PGE2), and IL-10, indicating the functional capacity of cultured microglia.

PMID- 11526956
TI  - Microglia in neuroregeneration.
AB  - Microglia has the potential to produce and release a range of factors that
      directly and/or indirectly promote regeneration in the injured nervous system.
      The overwhelming evidence indicates, however, that this potential is generally
      not expressed in vivo. Activated microglia may enhance neuronal degeneration
      following axotomy, thereby counteracting functional recovery. Microglia does not
      seem to contribute significantly to axonal outgrowth after peripheral nerve
      injury, since this process proceeds uneventful even if perineuronal microglia is
      eliminated. The phagocytic phenotype of microglia is highly suppressed during
      Wallerian degeneration in the central nervous system. Therefore, microglia is
      incapable of rapid and efficient removal of myelin debris and its putative growth
      inhibitory components. In this way, microglia may contribute to regeneration
      failure in the central nervous system. Structural and temporal correlations are
      compatible with participation by perineuronal microglia in axotomy-induced
      shedding of presynaptic terminals, but direct evidence for such participation is
      lacking. Currently, the most promising case for a promoting effect on neural
      repair by activated microglia appears to be as a mediator of collateral
      sprouting, at least in certain brain areas. However, final proof for a critical
      role of microglia in these instances is still lacking. Results from in vitro
      studies demonstrate that microglia can develop a regeneration supportive
      phenotype. Altering the microglial involvement following neural injury from a
      typically passive or even counterproductive state and into a condition where
      these cells are actively supporting regeneration and plasticity is, therefore, an
      exciting challenge and probably a realistic goal.

PMID- 11526957
TI  - Microglia in neurodegeneration: molecular aspects.
AB  - Inflammatory events in the CNS are associated with injuries as well as with well
      known chronic degenerative diseases, such as Multiple Sclerosis, Parkinson's, or
      Alzheimer's disease. Compared to inflammation in peripheral tissues, inflammation
      in brain appears to follow distinct pathways and time-courses, which likely has
      to do with a relatively strong immunosuppression in that organ. For this reason,
      it is of great importance to get insights into the molecular mechanism governing
      immune reactions in brain tissue. This task is hard to achieve in vivo, but can
      be approached by studying the major cell type responsible for brain inflammation,
      the microglia, in culture. Since these cells are the only professional antigen
      presenting cells resident in brain parenchyma, molecular mechanisms of antigen
      presentation are being discussed first. After covering the expression and
      regulation of anti- and proinflammatory cytokines, induction and regulation of
      two key enzymes and their products-COX-2 and iNOS-are summarized. Possibly,
      pivotal molecular targets for drug therapies of brain disorders will be
      discovered in intracellular signaling pathways leading to activation of
      transcription factors. Finally, the impact of growth factors, of neurotrophins in
      particular, is highlighted. It is concluded that the presently available data on
      the molecular level is far from being statisfying, but that only from better
      insights into molecular events will we obtain the information required for more
      specific therapies.

PMID- 11526958
TI  - Effect of the kappa-opioid receptor agonist, U69593, on reinstatement of
      extinguished amphetamine self-administration behavior.
AB  - Previous research has indicated that pretreatment with the kappa-opioid receptor
      agonist, U69593, decreased the ability of experimenter-administered cocaine to
      reinstate extinguished cocaine self-administration behavior. This effect was
      specific to cocaine-produced drug seeking since U69593 failed to attenuate the
      ability of experimenter-administered amphetamine to reinstate extinguished
      cocaine self-administration behavior. One possibility is that U69593 selectively
      attenuates the behavioral effects of the drug that was originally self
      administered. In order to test this hypothesis, the present study examined the
      effect of U69593 (0.0 or 0.32 mg/kg) on the reinstatement of extinguished
      amphetamine self-administration behavior produced by experimenter-administered
      injections of cocaine and amphetamine. Following extinction of amphetamine self
      administration (0.04 mg/kg/infusion) the ability of cocaine (0.0, 5.0, 10.0 or
      20.0 mg/kg) or amphetamine (0.0, 0.3, 1.0 or 3.0 mg/kg) to reinstate extinguished
      self-administration behavior was measured. Both drugs reinstated extinguished
      responding and the reinstatement was attenuated by pretreatment with U69593. The
      data indicate that the ability of U69593 to decrease drug seeking is not
      restricted to subjects experienced with cocaine self-administration. Self
      administration history does, however, determine the effect of U69593 on
      amphetamine-produced drug seeking.

PMID- 11526959
TI  - Analgesic efficacy of ketorolac and morphine in neonatal rats.
AB  - Ketorolac is a potent nonsteroidal antiinflammatory drug (NSAID). In adult humans
      and animals, its analgesic efficacy can be comparable to opiates. However, it has
      not been studied in neonatal animals. We conducted a blinded, controlled study
      comparing the effects of ketorolac and morphine in neonatal rats using the
      formalin model. Animals were given intraperitoneal (i.p.) injections of ketorolac
      or morphine at 3 or 21 days of age. Ketorolac had an analgesic and
      antiinflammatory effect in 21-day-old pups, but not in the 3-day-olds. Morphine
      had a significant analgesic, but no antiinflammatory effect at both ages. These
      results indicate that ketorolac is an effective analgesic agent in preweaning,
      but not neonatal rats. Opiates may be more appropriate analgesics in neonates.

PMID- 11526961
TI  - Effects of MDL 73005 on water-maze performances and locomotor activity in
      scopolamine-treated rats.
AB  - The stimulation of 5-HT1A receptors in the raphe or their blockade in the
      hippocampus can reduce cognitive deficits induced by blockade of muscarinic
      receptors in the hippocampus. We investigated the effects of MDL 73005 (8-[2-(2,3
      dihydro-1,4-benzodioxin-2-ylmethylamino) ethyl]-8-azaspiro[4,5] decane-7,9-dione
      methyl sulphonate), an agonist at 5-HT1A somatodendritic autoreceptors and an
      antagonist at postsynaptic 5-HT1A receptors in rats treated systemically with
      scopolamine. Spatial memory was assessed in a water maze using protocols testing
      reference and working memory. Home cage locomotor activity was also determined.
      Working memory and locomotor activity were evaluated before and after para
      chlorophenylalanine (pCPA) treatment. Scopolamine produced a weak impairment of
      reference memory at 0.5 mg/kg, and a more pronounced impairment of working memory
      at 0.25 and 0.5 mg/kg. MDL 73005 alone (2 mg/kg, i.p.) had no effect, but
      prevented the memory impairments induced by 0.25 mg/kg of scopolamine.
      Scopolamine induced hyperlocomotion. MDL 73005 alone did not affect locomotor
      activity, but exacerbated the hyperlocomotion induced by 0.5 mg/kg of
      scopolamine. pCPA did not abolish the effects of MDL 73005, suggesting that these
      effects were not due to an action at presynaptic receptors, or even that they
      involved receptors other than serotonergic ones (e.g., D2). In conclusion, MDL
      73005 is able to antagonise moderate spatial memory dysfunctions induced by
      systemic muscarinic blockade.

PMID- 11526960
TI  - Role of estrogen in the acquisition of intravenously self-administered cocaine in
      female rats.
AB  - Previous work from this laboratory has revealed that female rats acquired cocaine
      self-administration at a faster rate than male rats and that a greater percentage
      of females acquired self-administration [Psychopharmacology 144 (1999) 77.]. It
      has been suggested that sex differences in stimulant self-administration may be
      related to ovarian hormones, particularly estrogen. To investigate this
      possibility, we compared four groups (n = 10) of female rats: ovariectomized
      (OVX) treated with either estradiol benzoate (EB) or vehicle (VEH), and sham
      operated intact (SH) females treated with either the antiestrogen tamoxifen (TAM)
      or VEH. An autoshaping procedure was used to train rats to lever press for
      intravenous infusions of cocaine (0.2 mg/kg). The criterion for cocaine
      acquisition was a mean of 100 self-administered infusions over five consecutive 6
      h sessions. Results revealed that 70% of the OVX + EB group and 80% of the SH +
      VEH group acquired self-administration, while only 30% of the OVX + VEH group and
      50% of the SH + TAM group met the acquisition criterion. Rats that had estrogen
      chemically or surgically blocked exhibited significantly less responding for
      cocaine over the acquisition testing period, and fewer of these rats met the
      acquisition criterion compared to intact rats and to OVX rats with estrogen (EB)
      replacement. The percentages for females with estrogen (70% and 80%) vs. those
      without (OVX, 30%) were similar to those reported for intact females (70%) and
      males (30%) in the previous study [Psychopharmacology (2000)]. Taken together,
      these results suggest that estrogen is a key factor influencing drug-seeking
      behavior in female rats, and it may underlie sex differences in drug-reinforced
      responding.

PMID- 11526962
TI  - Amlodipine enhances the activity of antiepileptic drugs against
      pentylenetetrazole-induced seizures.
AB  - Amlodipine (AML), which belongs to the 1,4-dihydropyridine calcium channel
      antagonists, possesses pharmacological and pharmacokinetic profile that
      distinguishes it from other agents of this class. Pentylenetetrazole (PTZ)
      induced clonic and tonic convulsions in mice were significantly reduced by
      administration of AML at 10 mg/kg. At this dose AML remained without influence
      upon the plasma level of PTZ. The ED50 value of AML against clonic seizures
      induced by PTZ was 5.4 mg/kg. This calcium channel antagonist (at 2.5 mg/kg)
      combined with ethosuximide (ETX), valproate magnesium (VPA) or phenobarbital (PB)
      significantly reduced their ED50 values against clonic phase of PTZ-induced
      seizures. AML administered alone or in combination with antiepileptic drugs
      (AEDs) worsened the motor performance of mice in the chimney test. However, these
      treatments remained without significant influence on the retention time in the
      passive avoidance test. Plasma levels of antiepileptics remained unchanged in the
      presence of AML. The results indicate that AML does not seem a good candidate for
      a combination therapy in epileptic patients because of its adverse potential.

PMID- 11526963
TI  - Abnormal presynaptic catecholamine regulation in a hyperactive SNAP-25-deficient
      mouse mutant.
AB  - The consequences of a reduction in the presynaptic protein, SNAP-25, were
      investigated to determine the neurochemical basis of the marked hyperlocomotor
      activity in coloboma (Cm/+) mice. SNAP-25 is part of the minimal presynaptic
      machinery necessary for exocytotic neurotransmitter release. Reserpine treatment
      was used to deplete vesicular stores of catecholamines. Coloboma mice were more
      sensitive to the effects of reserpine than control mice. However, presynaptic
      regulation of dopamine (DA) release, as assessed by low-dose apomorphine
      challenge, was intact. There were region-specific reductions in in vivo tyrosine
      hydroxylation and the DA metabolites homovanillic acid (HVA) and 3,4
      dihydroxyphenylacetic acid (DOPAC) in the striatum and nucleus accumbens of Cm/+
      mice. While hyperactivity is often associated with changes in DA concentration,
      norepinephrine (NE) concentration was significantly increased in the striatum and
      nucleus accumbens of the hyperactive mutant. The increase in NE may regulate the
      hyperactivity in these mice, as suggested by current hypotheses of the mechanisms
      underlying attention-deficit hyperactivity disorder (ADHD) and Tourette's
      syndrome.

PMID- 11526964
TI  - The anxiolytic-like effect of MCI-225, a selective NA reuptake inhibitor with 5
      HT3 receptor antagonism.
AB  - We have previously reported that MCI-225, a selective noradrenaline (NA) reuptake
      inhibitor with serotonin (5-HT)3 receptor antagonism, shows antidepressant-like
      properties in experiments using rodents. In this study, we investigated the
      effect of MCI-225 in anxiety models in comparison with diazepam, ondansetron,
      maprotiline, imipramine, and trazodone. In social interaction (SI) test in rats,
      MCI-225 (10 and 30 mg/kg, p.o.), diazepam (1-10 mg/kg, p.o.), and a selective 5
      HT3 receptor antagonist ondansetron (1 mg/kg, p.o.) significantly increas

PMID- 11526965
TI  - Behavioral sensitization to ethanol in rats: evidence from the Sprague-Dawley
      strain.
AB  - Although it has been shown with other drugs of abuse, behavioral sensitization
      has not been shown with ethanol in rats. One possible reason for the negative
      previous findings may be due to the doses of ethanol employed in the different
      phases of sensitization. In the current experiment, outbred Sprague-Dawley rats
      were divided into either high or low responders to novelty. They were pretreated
      for 15 days with intraperitoneal injections of either saline or 1.0 g/kg ethanol,
      and then given a challenge dose of 0.25 g/kg ethanol after a 3-week period.
      During the first 10 min after the challenge dose, rats high in response to
      novelty pretreated with ethanol displayed higher locomotor activity scores
      relative to the other three groups. These data demonstrated evidence for
      behavioral sensitization with ethanol in outbred rats.

PMID- 11526966
TI  - Reliability of individual differences in initial sensitivity and acute tolerance
      to nitrous oxide hypothermia.
AB  - On average, the hypothermia exhibited by rats receiving 60% nitrous oxide (N2O)
      eventually abates despite the continued inhalation of the drug (i.e., acute
      tolerance develops). However, large individual differences occur in both the
      magnitude of hypothermia achieved and the degree of acute tolerance that
      develops. To determine whether the degree of temperature loss and subsequent
      recovery during N2O administration are reliable characteristics of an individual,
      we measured intraperitoneal temperature via telemetry in 77 Long-Evans rats that
      each received 60% N2O for 5 h during two sessions separated by 14 days. Good
      intersession reliability (Pearson's r) was observed for simple change and
      adjusted change scores for both initial N2O temperature sensitivity (.61 < or = r
      < or = .62), and acute tolerance development (.46 < or = r < or = .52). In a
      separate experiment, three groups of rats were selected based on their individual
      body temperature patterns during an initial N2O administration: (1) insensitive
      to N2O hypothermia (n = 8); (2) marked hypothermia followed by acute tolerance
      development (n = 6); and (3) marked hypothermia followed by little acute
      tolerance development (n = 6). When retested 10 days later, each group exhibited
      a body temperature profile similar to that observed during the initial N2O
      exposure. Thus, the temperature profile observed during a rat's initial exposure
      to 60% N2O reflects a reproducible response for that animal.

PMID- 11526967
TI  - A dopamine partial agonist and antagonist block amphetamine self-administration
      in a progressive ratio schedule.
AB  - A recently characterized class of compounds, dopamine partial agonists, have been
      suggested as potential therapeutic candidates for pharmacological intervention in
      psychostimulant addiction. These drugs bind to dopamine receptors with high
      affinity and low intrinsic activity and are thought to behave as functional
      antagonists in conditions of high dopaminergic tone, and as agonists in
      conditions of low receptor occupancy by dopamine. The aim of the present study
      was to characterize the effects of terguride, a partial dopamine agonist at the
      D2 receptor subtype, on intravenous self-administration of amphetamine in a
      progressive ratio schedule and to compare it with the effects produced by the
      dopamine D2 antagonist eticlopride and the dopamine D2 full agonist quinpirole.
      Terguride at the doses of 0.2 and 0.4 mg/kg i.p. significantly decreased the
      maximum number of responses delivered for a single injection of amphetamine
      ("breaking point"), an effect similar to that produced by the antagonist
      eticlopride (0.01-0.1 mg/kg s.c.). In contrast, administration of quinpirole (0.1
      1 mg/kg s.c.) did not significantly modify the breaking point for amphetamine
      responding. Also, terguride dose-dependently increased responding for amphetamine
      self-administration on a continuous reinforcement schedule. These data further
      confirm the effects of terguride on psychostimulant self-administration and
      indicate that under these conditions partial dopamine agonists act as functional
      dopamine receptor antagonists.

PMID- 11526968
TI  - D1 but not D2 dopamine receptor antagonism blocks the acquisition of a flavor
      preference conditioned by intragastric carbohydrate infusions.
AB  - The effects of dopamine D1 (SCH23390) and D2 (raclopride) receptor antagonists on
      the acquisition and expressions of flavor preferences conditioned by the
      postingestive actions of sucrose were investigated. Food-restricted rats were
      trained in one-bottle sessions to associate one flavored saccharin solution (CS+)
      with intragastric (i.g.) infusions of 16% sucrose, and another flavored saccharin
      solution (CS-) with water infusions. Flavor preferences were then measured in two
      bottle tests. In Experiment 1A, rats that received the D2 antagonist (raclopride,
      200 nmol/kg; RAC group) throughout training consumed less CS+ and CS- than did
      saline-treated Control rats; a saline-treated Yoked group had its intake limited
      to that of the RAC group. All three groups displayed CS+ preferences during two
      bottle tests when treated with saline or raclopride, except at doses that greatly
      suppressed intake. Experiment 1B obtained similar results with rats treated with
      400 nmol/kg raclopride throughout training. In Experiment 2, rats that received
      the D1 antagonist (SCH23390, 200 nmol/kg; SCH group) throughout training consumed
      less CS+ and CS- than did saline-treated Control rats; a saline-treated Yoked
      group had its intake limited to that of the SCH group. Unlike the Control and
      Yoked groups, the SCH group failed to prefer the CS+ to the CS- in two bottle
      tests. SCH23390 treatment during two-bottle testing did not block CS+ preference
      in the Control or Yoked groups, except at doses that greatly suppressed intake.
      We conclude that D1, but not D2, dopamine receptors are critically involved in
      the acquisition of a sucrose-conditioned flavor preference, and both receptor
      subtypes have a more limited role in the expression of this preference.

PMID- 11526969
TI  - Diazepam fails to potentiate GABA-induced chloride uptake and to produce
      anxiolytic-like action in aged rats.
AB  - The pharmacological response to benzodiazepines has been demonstrated to be
      different in aged individuals in comparison to adults. We studied the age
      dependent changes in some of the in vitro and behavioral effects of diazepam in
      aged (24 months old) rats, comparing them to adults (3 months old). We evaluated
      the in vitro gamma-aminobutyric acid (GABA)-induced 36Cl- uptake and the diazepam
      potentiation of GABA-stimulated 36Cl- uptake in microsacs from cerebral cortex of
      both groups of animals. We found no differences in the GABA-stimulated 36Cl-
      uptake between adult and aged animals, and diazepam failed to potentiate GABA
      induced 36Cl- flux in the aged cortical microsacs. We also examined the effect of
      0.03-10 mg of diazepam on locomotor activity in an open-field test and the
      anxiolytic-like action of diazepam in doses ranging from 0.03 to 1 in a dark
      light transition test. We observed no anxiolytic-like action of the drug in the
      dark-light transition test in the aged rats, while there was a shift to the left
      in the diminution of locomotor activity evaluated by the open-field test. We
      conclude that the pharmacodynamic changes observed in cortical GABA(A) receptors
      in aged rats could partially explain the lack of anxiolytic-like action but not
      the oversedation evidenced in this group of animals.

PMID- 11526970
TI  - Lesions of the posterior basolateral amygdala block feeding induced by systemic 8
      OH-DPAT.
AB  - We have recently reported that bilateral electrolytic lesions of the
      posterodorsal amygdala (PDA) in female rats which induce protracted overeating
      and weight gain also attenuate short-term feeding stimulated by intraraphe
      infusions of the serotonin (5-HT) 1A agonist, (+/-)-8-hydroxy-2-(di-n
      propylamino)tetralin, (8-OH-DPAT). Bilateral lesions of the posterior basolateral
      amygdala (pBLA) in male rats have also been reported to enhance feeding and
      weight gain, but much less so than PDA lesions do in female rats. The present
      study was performed to determine if pBLA lesions in female rats might attenuate 8
      OH-DPAT feeding and what, if any, relationship exists between 8-OH-DPAT-induced
      feeding and lesion-induced weight gain. Lesioned rats showed reliable increases
      in 24-h food intake and weight gain relative to shams during the days between
      surgery and acute drug-induced feeding tests. 8-OH-DPAT (0, 60, 120 or 240
      microg/kg in saline) increased feeding of shams in a dose-dependent manner over 2
      h. Feeding at the most effective dose (120 microg/kg) was reduced to vehicle
      levels in lesioned rats. The feeding induced by this dose correlated inversely
      (r=-.59, P<.01) with the magnitude of weight gained following lesions. Feeding at
      the highest dose (240 microg/kg) showed a biphasic effect of feeding inhibition
      over the first vs. second hour that was unaffected by lesions. These findings
      imply that either fibers of passage and/or cellular elements in both the PDA and
      pBLA normally inhibit overeating and weight gain via intact serotonergic
      mechanisms.

PMID- 11526971
TI  - Histamine and selective H3-receptor ligands: a possible role in the mechanism and
      management of epilepsy.
AB  - The interaction of selective histamine H3-receptor agonist R(alpha)-methyl
      histamine (RAMH) and antagonist thioperamide (THP) with some antiepileptic drugs
      [AED; phenytoin (PHT), carbamazepine (CBZ), sodium valproate (SVP), and
      gabapentin (GBP)] was studied on seizures induced by maximal electroshock (MES)
      and pentylenetetrazole (PTZ) in mice. It was found that subeffective dose of THP
      in combination with the subeffective doses of PHT and GBP provided protection
      against MES and/or PTZ-induced seizures. Further, RAMH reversed the protection
      afforded by either PHT or GBP on MES and/or PTZ seizures. In another set of
      experiments, the histamine content was measured in the whole brain and in
      different brain regions including cerebral cortex, hypothalamus, brain stem and
      cerebellum following convulsant (MES and PTZ) and AED treatment. It was seen that
      while MES exhibited a tendency to enhance brain histamine levels, PTZ showed the
      opposite effect. AEDs either increased (PHT and GBP) or decreased (SVP) brain
      histamine content in different regions to varying degrees. The results indicate a
      role for histamine in seizures and in the action of AEDs and suggest that
      selective H3-receptor antagonists may prove to be of value as adjuncts to
      conventional AEDs.

PMID- 11526972
TI  - Developmental lead exposure in rats: is a behavioral sequel extended at F2
      generation?
AB  - Lead toxicity was studied in rats exposed from conception until weaning and
      assessed by monitoring offspring behavior in both the open field and elevated
      plus maze and by determining tissue lead in an assessment schedule extended to
      first (F1) and second (F2) generations. Dams utilized for the F1 generation were
      submitted to 750 ppm of lead (acetate) in drinking water during pregnancy and
      lactation. For F1 pups, behavioral alterations were not detected in the elevated
      plus maze, while in the open field, spontaneous locomotor activity as well as
      time of both grooming and rearing increased, while freezing time decreased in 30-
      and 90-day-old rats. Lead content was higher in tissues of 1- and 30-day-old
      pups. However, in 90-day-old rats, lead was detected only in the femur. F2
      generation was lead-free but still presented alterations in both locomotor
      activity and grooming in 30- and 90-day-old pups. It appears that developmental
      lead exposure may cause behavioral effects during the developmental stage of the
      F1 generation, which remains throughout the animal's adult life as a sequel,
      regardless of lead accumulation, and is extended to the F2 generation of rats.

PMID- 11526973
TI  - Prepulse inhibition of the acoustic startle response in cocaine-withdrawn rats.
AB  - Prepulse inhibition (PPI) of startle is a sensorimotor gating task in which a low
      intensity acoustic stimulus presented prior to a high-intensity, startle
      eliciting stimulus can attenuate the acoustic startle response (ASR). Previous
      studies on startle reactivity in cocaine-withdrawn rats have found minimal
      changes; the present study extends this work to the gating of ASR. In Experiment
      1, rats were injected daily with either saline or cocaine (30 mg/kg i.p.) for 2
      weeks. ASR and PPI were measured prior to, and at 3- and 14-day withdrawal from,
      the chronic treatment. No effect of cocaine treatment was found on either
      measure. In Experiment 2, treatment was extended to 8 weeks, and an earlier
      withdrawal time point (1 day) was added. Rats treated with cocaine for 8 weeks
      exhibited lower startle reactivity during withdrawal compared with saline-treated
      controls. PPI did not differ between treatment groups. Thus, extended chronic
      treatment with cocaine rendered significant effects on startle responsivity.
      Further, this finding mirrors the blunted ASR exhibited in chronic cocaine users
      [Neuropsychopharmacology 22 (2000) 89.].

PMID- 11526974
TI  - Opioid receptor involvement in the adaptation to motion sickness in Suncus
      murinus.
AB  - The aim of the present study was to investigate an opioid receptor involvement in
      the adaptation response to motion sickness in Suncus murinus. Different groups of
      animals were treated intraperitoneally with either saline, morphine (0.1 and 1.0
      mg/kg), naloxone (1.0, 10.0 and 5.0 mg/kg) or a combination of naloxone plus
      morphine in the absence or 30 min prior to a horizontal motion stimulus of 1 Hz
      and 40 mm amplitude. For the study of adaptation, different groups received
      saline on the first trial, and in subsequent trials (every 2 days) they received
      either saline, naloxone (1.0 and 10.0 mg/kg, i.p.) or morphine (0.1 mg/kg, i.p.)
      30 min prior to the motion stimulus. Pretreatment with morphine caused a dose
      related reduction in emesis induced by a single challenge to a motion stimulus.
      Pretreatment with naloxone alone did not induce emesis in its own right nor did
      it modify emesis induced by a single challenge to a motion stimulus. However,
      pretreatment with naloxone (5.0 mg/kg, i.p.) revealed an emetic response to
      morphine (P<.001) (1.0 mg/kg, i.p.) and antagonised the reduction of motion
      sickness induced by morphine. In animals that received saline or naloxone (1.0
      mg/kg), a motion stimulus inducing emesis decreased the responsiveness of animals
      to a second and subsequent motion stimulus challenge when applied every 2 days
      for 11 trials. However, the animals receiving naloxone 10.0 mg/kg prior to the
      second and subsequent challenges showed no significant reduction in the intensity
      of emesis compared to the first trial. The data are revealing of an emetic
      potential of morphine when administered in the presence of a naloxone
      pretreatment. The administration of naloxone is also revealing of an additional
      inhibitory opioid system whose activation by endogenous opioid(s) may play a role
      in the adaptation to motion sickness on repeated challenge in S. murinus.

PMID- 11526975
TI  - Different treatment regimens and the development of tolerance to nicotine's
      anxiogenic effects.
AB  - The effects of different treatment regimens were investigated on the development
      of tolerance to the anxiogenic effect of nicotine (0.45 mg/kg) in the social
      interaction test of anxiety. Rats received nicotine (0.45 mg/kg/day) by
      intravenous injections (5 days/week), subcutaneous injections (5 or 7 days/week)
      or continuous infusion by osmotic minipump. In all groups, 4 days of nicotine
      treatment resulted in significant decreases in social interaction compared with
      the vehicle control groups, without changes in locomotor activity, indicating a
      specific anxiogenic effect. These significant anxiogenic effects persisted even
      after 4 weeks of treatment although they were less marked, indicating development
      of partial tolerance. No significant changes in the time spent in social
      interaction were found when rats were tested undrugged 24 and 72 h after the
      termination of nicotine treatment. There was no evidence that the treatment
      regimen affected the rate of development of tolerance, despite very different
      peak plasma nicotine concentrations.

PMID- 11526976
TI  - Role of central histaminergic system in lorazepam withdrawal syndrome in rats.
AB  - Effects of histaminergic agonists and antagonists were investigated on withdrawal
      signs in lorazepam-dependent rats. Physical dependence was developed by giving
      lorazepam admixed with the food in the following dose schedule (in mg/kg given
      daily x days): 10 x 4, 20 x 4, 40 x 4, 80 x 4, and 120 x 7. The parameters
      observed during the periods of administration of lorazepam and after its
      withdrawal were spontaneous locomotor activity (SLA), reaction time to pain, foot
      shock aggression (FSA), and audiogenic seizures. During the withdrawal period,
      the rats were divided into groups of 10 each. Control-withdrawal group did not
      receive any drug. The drugs (in mg/kg administered intramuscularly)--L-histidine
      (50), histamine-N-methyl (2), promethazine (10), pheniramine (10), astemizole
      (10), and thioperamide (1)--were given separately in other groups daily during
      the withdrawal period. The withdrawal signs in control group were hyperkinesia,
      hyperaggression, and audiogenic seizures. L-Histidine, precursor of histamine,
      and thioperamide, antagonist of H3 receptor, potentiated hyperkinesia,
      hyperaggression, and audiogenic seizures. Histamine-N-methyl, agonist of H3
      receptor, and H1 receptor antagonists, promethazine and pheniramine, blocked all
      the withdrawal signs. Astemizole, a peripheral antagonist of H1 receptor, could
      not affect any withdrawal sign. It may be concluded that histamine H1 receptors
      are facilitatory and H3 receptors are inhibitory for benzodiazepine (BZD)
      withdrawal syndrome.

PMID- 11526977
TI  - Characterization of the analgesic properties of nomifensine in rats.
AB  - The analgesic properties of the catecholamine uptake inhibitor nomifensine were
      investigated in the tail immersion, hot plate and formalin tests. Systemic
      administration of nomifensine produced analgesia only in the formalin test. The
      analgesia was dose-dependent (0.625-5 mg/kg), and the highest dose completely
      abolished nociceptive behaviors induced by 2% formalin. The analgesia was not
      affected by the opioid antagonist naltrexone (2.5-40 microg s.c.) but was dose
      dependently reversed by the D2 antagonist eticlopride (181.3-270 microg/kg i.p.).
      Neither naltrexone nor eticlopride affected formalin pain scores. Nomifensine
      analgesia appears to be dopamine-mediated but independent of opioid mechanisms.

PMID- 11526978
TI  - Comparison of N2O- and chlordiazepoxide-induced behaviors in the light/dark
      exploration test.
AB  - Earlier research has demonstrated similarities in the behavioral effects of
      nitrous oxide (N2O) and benzodiazepine (BZ) drugs such as chlordiazepoxide (CP).
      The present research was conducted to compare the behavioral effects of N2O and
      CP in mice in the light/dark exploration test. When challenged with either N2O or
      CP, mice exhibited significant dose-dependent increases in the time spent in the
      light compartment and also in the number of transitions between the light and
      dark compartments. Pretreatment with BZ receptor antagonist flumazenil (FLU), the
      GABA(A) receptor antagonist SR-95531 or the selective neuronal nitric oxide (NO)
      synthase (nNOS) inhibitor 7-nitroindazole (7-NI) all antagonized anxiolytic
      effects of N20 and CP. Based on these findings, it was concluded that N20 and CP
      evoke similar behavioral effects in the light/dark exploration test that are
      similar in their interaction with BZ and GABA(A) receptor antagonists. There also
      appears to be a specific role for nNOS in generating the NO involved in mediation
      of these effects.

PMID- 11526979
TI  - Adenosine agonists CGS 21680 and NECA inhibit the initiation of cocaine self
      administration.
AB  - Administration of the adenosine antagonist caffeine will facilitate the
      reinstatement of cocaine self-administration responding. This suggests that
      adenosine receptors may play a role in the motivational systems that regulate
      cocaine-seeking behaviors. If so then adenosine agonists may act to block cocaine
      self-administration. To test this hypothesis, the effects of the nonselective
      adenosine agonist NECA and of the A2A selective agonist, CGS 21680 on the self
      administration of cocaine were determined. In these experiments, rats were
      allowed to obtain intravenous cocaine infusions (0.6 mg/kg/infusion) delivered
      under a Fixed Ratio 5 schedule. Treatment with either NECA or CGS 21680 in
      comparison to vehicle administration reduced the number of infusions received per
      session. This, primarily, was due to a marked increase in the latency for
      delivery of the first cocaine infusion. Responding after drug-induced delays
      tended to be at control levels. Adenosine agonists are known to have sedative
      effects and these actions might play a role in NECA and CGS 21680-induced
      increases in latencies for cocaine delivery. These results indicate that the
      administration of adenosine agonists may inhibit cocaine-seeking behaviors. The
      degree to which these actions are on motivational systems as opposed to involving
      less specific effects remains to be fully elucidated.

PMID- 11526980
TI  - Alcohol place preference conditioning in high- and low-alcohol preferring
      selected lines of mice.
AB  - High- and low-alcohol preferring (HAP and LAP) selected lines of mice diverge
      greatly in free-choice alcohol consumption. This study investigated whether the
      lines differ in a measure of alcohol reward not dependent on drinking,
      specifically place conditioning. Mice were subjected to a differential
      conditioning procedure in which four alcohol-paired CS+ trials on one floor cue
      (0, 1.5, 3, or 4 g/kg; ns=20-24) alternated with four saline-paired CS- trials on
      a different floor cue. Testing was on a split floor, half CS+ and half CS-. HAP
      and LAP mice showed no preference at 0 g/kg, and equivalent, moderate preference
      at 1.5 and 3 g/kg alcohol. At 4 g/kg, LAP, but not HAP mice showed an increase in
      preference. The present findings imply greater efficacy of alcohol preference
      conditioning in LAP mice, but do not speak for line differences in sensitivity.
      Results do not support the hypothesis that selection for high drinking yields
      greater efficacy of alcohol as a reinforcer when reward is measured using a
      technique that does not rely on drinking. Low drinking in LAP mice may emerge
      from innate taste avoidance of alcohol as a result of selective breeding for low
      preference, which prevents them from encountering alcohol's rewarding,
      pharmacological effects.

PMID- 11526981
TI  - Strain and model differences in behavioral outcomes after spinal cord injury in
      rat.
AB  - Spinal cord injury (SCI) results in loss of function below the level of injury
      and the development of chronic central pain (CCP) syndromes. Since different
      strains may develop and express chronic pain behaviors differently, we evaluated
      behavioral outcomes (locomotor recovery and the development of mechanical and
      thermal allodynia) in three commonly used strains of rats (Long-Evans, Wistar,
      and Sprague-Dawley) using two models of SCI. The two models examined were
      contusion at T10 (NYU impactor, 12.5 mm height) and the T13 hemisection.
      Mechanical stimulation (von Frey filaments) revealed significantly lower baseline
      responses for Long-Evans rats and significantly higher baseline paw withdrawal
      latencies to thermal stimulation for Wistar rats compared to the other strains.
      Following contusion SCI, Long-Evans rats had the highest percentage of animals
      that developed mechanical allodynia (73%), while Sprague-Dawley rats had the
      highest percentages (75%) following hemisection SCI. Interestingly, the Sprague
      Dawley rats had the highest percentage (87%) to develop thermal allodynia
      following contusion SCI, while 100% of both Long-Evans and Sprague Dawley rats
      developed thermal allodynia in the hemisection model. Locomotor recovery after
      SCI was similar for each model in that Long-Evans rats recovered slower and to a
      lesser extent than the other strains. In each model, Sprague-Dawley rats
      recovered faster and achieved greater function. Overall, the hemisection model
      produced a larger percentage of animals that developed CCP and had greater
      responses to mechanical stimulation. Thus, it appears that strain selection has a
      greater impact on locomotor recovery and model selection has a greater impact on
      the development of CCP following SCI. Furthermore, these results suggest that
      genetic factors may play a role in recovery following SCI.

PMID- 11526982
TI  - Effects of 4-aminopyridine on motor evoked potentials in patients with spinal
      cord injury: a double-blinded, placebo-controlled crossover trial.
AB  - 4-Aminopyridine (4-AP) is a potassium (K+) channel blocking agent that has been
      shown to reduce the latency and increase the amplitude of motor evoked potentials
      (MEPs) elicited with transcranial magnetic stimulation (TMS) in patients with
      chronic spinal cord injury (SCI). These effects on MEPs are thought to reflect
      enhanced conduction in long tract axons brought about by overcoming conduction
      deficits due to focal demyelination and/or by enhancing neuroneuronal
      transmission at one or more sites of the neuraxis. The present study was designed
      to obtain further evidence of reduced central motor conduction time (CMCT) and to
      determine whether MEPs could be recorded from paretic muscles in which they were
      not normally elicited. MEPs were elicited with TMS being delivered to subjects (n
      = 25) pre- and post-administration of 4-AP (10 mg capsule) or placebo. The
      principal finding was that 4-AP lowered the stimulation threshold, increased the
      amplitude and reduced the latency of MEPs in all muscles tested, including those
      that were unimpaired, but did not alter measures of the peripheral nervous system
      (i.e., M-wave, H-reflex, F-wave). These 4-AP-induced changes in MEPs were
      significantly greater than those seen with placebo (p < 0.05). The primary
      implication of these results is that a low dose of 4-AP (immediate-release
      formulation) appears to improve the impaired central motor conduction of some
      patients with incomplete SCI. This is most likely attributable to overcoming
      conduction deficits at the site of injury but may also involve an increase in
      cortical excitability.

PMID- 11526983
TI  - Intrathecal levels of complement-derived soluble membrane attack complex (sC5b-9)
      correlate with blood-brain barrier dysfunction in patients with traumatic brain
      injury.
AB  - It has become evident in recent years that intracranial inflammation after
      traumatic brain injury (TBI) is, at least in part, mediated by activation of the
      complement system. However, most conclusions have been drawn from experimental
      studies, and the intrathecal activation of the complement cascade after TBI has
      not yet been demonstrated in humans. In the present study, we analyzed the levels
      of the soluble terminal complement complex sC5b-9 by ELISA in ventricular
      cerebrospinal fluid (CSF) of patients with severe TBI (n = 11) for up to 10 days
      after trauma. The mean sC5b-9 levels in CSF were significantly elevated in 10 of
      11 TBI patients compared to control CSF from subjects without trauma or
      inflammatory neurological disease (n = 12; p < 0.001). In some patients, the
      maximal sC5b-9 concentrations were up to 1,800-fold higher than in control CSF.
      The analysis of the extent of posttraumatic blood-brain barrier (BBB)
      dysfunction, as determined by CSF/serum albumin quotient (Q(A)), revealed that
      patients with a moderate to severe BBB impairment (mean Q(A) > 0.01) had
      significantly higher intrathecal sC5b-9 levels as compared to patients with
      normal BBB function (mean Q(A) < 0.007; p < 0.0001). In addition, a significant
      correlation between the individual daily Q(A) values and the corresponding sC5b-9
      CSF levels was detected in 8 of 11 patients (r = 0.72-0.998; p < 0.05). These
      data demonstrate for the first time that terminal pathway complement activation
      occurs after head injury and suggest a possible pathophysiological role of
      complement with regard to posttraumatic BBB dysfunction.

PMID- 11526984
TI  - Neurochemical characterization of traumatic brain injury in humans.
AB  - Trauma is the leading cause of death in individuals between the ages of 1 and 44
      years. And, in the case of severe head injury mortality can reach as high as 35
      70%. Despite this fact, there has been little progress in the development of
      effective pharmacological agents to protect brain injured patients. To date,
      there is little data on the mechanisms involved in neuronal cellular insult after
      severe head injury, especially in humans. Glutamate acts both as a primary
      excitatory neurotransmitter and a potential neurotoxin within the mammalian
      brain. Evidence indicates that hyperactivity of the glutamate system contributes
      to neuronal death in brain trauma. Also, in animal models of neurotrauma, this
      neural injury is followed by gliosis which has been linked to the severity of
      brain injury. To investigate the glutamate system in brain trauma, we carried out
      [3H]glutamate and [3H]MK801 (a noncompetitive NMDA-receptor antagonist) binding
      and [3H]glutamate uptake assays in human cerebral cortex preparations obtained
      from severely brain injured and control victims. Additionally, to investigate
      gliosis following brain injury, we performed GFAP immunohistochemistry. There
      were no significant differences in [3H]glutamate binding (affinity or density of
      sites) between the control and head injured groups. In contrast, cerebral
      cortical [3H]MK801 binding revealed both a significant increase in the density of
      sites (Bmax) and a decrease in the dissociation constant (Kd) in the head injured
      group when compared to controls. There were no significant differences in
      [3H]glutamate uptake between groups. The injured brains presented an increased
      number of GFAP-positive astrocytes and more intense GFAP reaction in comparison
      to control brains. In the context of traumatic brain injury, our results
      encourage further investigation into compounds capable of selective modulation of
      NMDA receptor subtype in humans while also therapeutically manipulating glial
      cell responses following brain trauma.

PMID- 11526985
TI  - Enhanced lipid peroxidation processes in patients after brain contusion.
AB  - Erythrocyte superoxide dismutase (SOD-1) activity and cerebrospinal fluid (CSF),
      blood plasma low-density lipoprotein (LDL) and erythrocyte thiobarbituric acid
      reactive substance (TBARS) concentrations were determined in 30 patients with
      brain contusion and in 37 control patients with low back pain due to
      noninflammatory degenerative lumbar disc disease. In comparison to controls,
      during 10-day follow-up patients with brain contusion had significantly increased
      erythrocyte SOD-1 activity and CSF, blood plasma (LDL), and erythrocyte TBARS
      concentrations. The highest CSF TBARS concentrations were observed in five
      patients who died 2, 7, or 8 days following head injury. A significant negative
      correlation was found between erythrocyte SOD-1 activity or TBARS concentrations,
      in the blood plasma LDL fraction and erythrocytes, and The Glasgow Coma Scale
      score. These results suggest that enhanced lipid peroxidation processes, which
      seem to correlate with the severity of head injury, accompany brain contusion.

PMID- 11526986
TI  - Upregulation of iNOS expression and phosphorylation of eIF-2alpha are paralleled
      by suppression of protein synthesis in rat hypothalamus in a closed head trauma
      model.
AB  - When the inducible form of nitric oxide synthase (iNOS) is expressed after
      challenge to the nervous system, it results in abnormally high concentrations of
      nitric oxide (NO). Under such conditions, NO could phosphorylate the eukaryotic
      translation initiation factor (eIF)-2alpha, thus suppressing protein synthesis in
      neurons that play a role in endocrine and autonomic functions. Using the Marmarou
      model of traumatic brain injury (TBI), we observed a rapid increase (at 4 h after
      TBI) of iNOS mRNA in magno- and parvocellular supraoptic and paraventricular
      neurons, declining gradually by approximately 30% at 24 h and by approximately
      80% at 48 h. Western analysis indicated a trend towards increased iNOS protein
      synthesis at 4 h, which peaked at 8 h, and tended to decrease at the later time
      points. At the same time points, we detected immunocytochemically the
      phosphorylated form of eIF-2alpha (eIF-2alpha[P]) as cytoplasmic and more often
      as nuclear labeling. The incidence of double-labeled [iNOS and eIF-2alpha(P)]
      neuronal profiles, particularly at 24 h and 48 h after TBI, was high. De novo
      protein synthesis assessed quantitatively after infusion of 35S
      methionine/cysteine was reduced by approximately 20% at 4 h, remained depressed
      at 24 h, and did not return to control levels up to 48 h following the trauma.
      The results suggest that iNOS may trigger phosphorylation of eIF-2alpha, which in
      turn interferes with protein synthesis at the translational (ribosomal complex)
      and transcriptional (chromatin) levels. The depression in protein synthesis may
      include downregulation of iNOS itself, which could be an autoregulatory
      inhibitory feedback mechanism for NO synthesis. Excessive amounts of NO may also
      participate in dysfunction of hypothalamic circuits that underlie endocrine and
      autonomic alterations following TBI.

PMID- 11526987
TI  - Intraarterial administration of marrow stromal cells in a rat model of traumatic
      brain injury.
AB  - To test the efficacy of various delivery routes of stem cells to treat cerebral
      injury, we investigated the parenchymal distribution of marrow stromal cells
      (MSCs) injected into the internal carotid artery (ICA) of the adult rat after
      traumatic brain injury (TBI). Bromodeoxyuridine (BrdU)-labeled MSCs were injected
      via the ipsilateral ICA at 24 h after TBI. Using histology and
      immunohistochemistry, the distribution of implanted MSCs was analyzed at 7 days
      after transplantation. Four groups (n = 4/group) were studied: group 1, animals
      transplanted with MSCs cultured with NGF and BDNF at 24 h after TBI; group 2,
      animals transplanted with MSCs cultured without NGF and BDNF; group 3, animals
      injected with a placebo, phosphate buffered saline into the ICA at 24 h after
      TBI; and group 4, rats subjected to TBI only. In groups 1 and 2, BrdU-positive
      cells were localized to the boundary zone of the lesion, corpus callosum and
      cortex of the ipsilateral hemisphere. The number of BrdU-positive cells was
      significantly higher in the ipsilateral hemisphere than in the contralateral
      hemisphere. More MSCs infused intraarterially engrafted in group 1 (18.9%) than
      in group 2 (14.4%, p < 0.05). Using double staining, BrdU-positive cells
      expressed MAP-2, NeuN, and GFAP in both groups 1 and 2, with this expression
      being greater in group 1 and the difference between two groups reaching
      statistical significance in case of MAP-2. Our data suggest that intraarterial
      transplantation of MSCs is a viable route for the intracerebral administration of
      MSCs for the treatment of TBI, since MSCs infused intraarterially after TBI
      survive and migrate into the brain. Some implanted MSCs express proteins specific
      to neurons and astrocytes. The addition of NGF and BDNF promote migration of MSCs
      into the brain and subsequent expression of neuronal protein MAP-2.

PMID- 11526988
TI  - Free radical scavenger posttreatment improves functional and morphological
      outcome after fluid percussion injury in the rat.
AB  - Reactive oxygen species (ROS) are thought to contribute to the secondary injury
      process after traumatic brain injury (TBI). ROS scavenging compounds have shown
      neuroprotective properties in various models of experimental brain injury,
      including TBI. Administration of nitrone radical scavengers has emerged as a
      promising pharmacological concept in focal experimental ischemia due to their low
      toxicity and neuroprotective properties, with a time window of several hours. The
      aim of this study was to test the neuroprotective efficacy of two nitrones, the
      readily blood-brain barrier (BBB) penetrating alpha-phenyl-N-tert-butyl nitrone
      (PBN) and the poorly BBB penetrating sulfo-derivative, 2-sulfo-phenyl-N-tert
      butyl nitrone (S-PBN) after moderate (2.20-2.45 atm) lateral fluid percussion
      injury (FPI) in rats. Twenty-six rats received a 24-h intravenous infusion (30
      mg/kg/h) of saline, PBN, or an equimolar dose of S-PBN beginning 30 min after
      FPI. Eight sham-operated animals were used as controls. Cognitive function was
      assessed using the Morris Water Maze at day 11-15 after TBI, neurological status
      at day 1, 4, and 8 and morphological outcome at day 15. PBN and S-PBN treatment
      significantly reduced the loss of ipsilateral hemispheric tissue whereas only S
      PBN tended to reduce the cortical lesion volume. PBN treatment caused a
      significant improvement in the neurological score as compared to saline-treated
      animals, while S-PBN alone attenuated the cognitive deficit. Our results suggest
      that nitrone radical scavengers are neuroprotective when administered 30 min
      after FPI in rats. Differences in pharmacokinetics may account for the observed
      individual neuroprotective profiles of the two nitrones.

PMID- 11526989
TI  - Bradykinin B2, but not B1, receptor antagonism has a neuroprotective effect after
      brain injury.
AB  - The aim of the present study was to measure the therapeutic effects of bradykinin
      antagonists on lesion volume and brain swelling induced by cold injury in the
      parietal cortex of rat and mouse, respectively. Cold lesion was induced by
      application of a precooled (-78 degrees C) copper cylinder (3 mm diameter) to the
      intact dura of rat and mouse for 6 and 30 sec, respectively. At 24 h after the
      injury, the brains were removed and lesion volume was determined by the
      triphenyltetrazolium chloride method in rats. In the mouse, brain swelling was
      expressed as percentage increase in weight of the injured hemisphere which is
      compared to the contralateral side. After a subcutaneous priming dose of 18
      microg/kg, a 1-h pretreatment and 24-h posttreatment using osmotic minipumps (300
      ng/kg x min) was applied. Hoe140, a bradykinin receptor 2 antagonist, revealed a
      19% reduction of lesion volume (p < 0.05) in the rat and a 14% diminution of
      brain swelling (p < 0.05) in the mouse. In contrast, the bradykinin receptor 1
      antagonist, B 9858, had no effect on lesion volume compared to sham treated rats.
      When B 9858 was given in combination with Hoe140, a significant reduction in
      lesion volume was seen which was equivalent to and not different from that seen
      with Hoe140 alone in the rat. We conclude that brain injury after cold lesion is
      partially mediated by bradykinin and can be successfully treated with B2
      antagonists.

PMID- 11526990
TI  - Small shifts in craniotomy position in the lateral fluid percussion injury model
      are associated with differential lesion development.
AB  - Previous studies have shown that location and direction of injury may affect
      outcome in experimental models of traumatic brain injury. Significant variability
      in outcome data has also been noted in studies using the lateral fluid percussion
      brain injury model (FPI) in rats. In recent studies from our laboratory, we
      observed considerable variability in localization and severity of tissue damage
      as a function of small changes in craniotomy position. To further address this
      issue, we examined the relationship between craniotomy position and brain lesion
      size/location in rats subjected to moderate FPI (2.28 +/- 0.18 atmospheres). With
      placement of a 5-mm craniotomy adjacent to the sagittal suture, there was both
      ipsilateral and contralateral damage as detected at 3 weeks posttrauma using T2
      weighted magnetic resonance imaging (MRI). The MRI lesions were generally
      restricted to the hippocampus and subcortical layers. Shifting of the craniotomy
      site laterally was associated with increased ipsilateral tissue damage and a
      greater cortical component that correlated with distance from the sagittal
      suture. In contrast, the contralateral MRI lesion did not change significantly in
      size or location unless the center of the craniotomy was placed more than 3.5 mm
      from the sagittal suture, under which condition contralateral damage could no
      longer be detected. Ipsilateral tissue damage as determined from the MRI scans
      was linearly correlated to motor outcome but not with cognitive outcome as
      assessed by the Morris Water Maze. We conclude that craniotomy position is
      critical in determining extent and location of tissue injury produced during the
      lateral FPI model in rats. Addressing such potential variability is essential for
      studies that address either injury mechanisms or therapeutic treatments.

PMID- 11526991
TI  - Source distribution of neuromagnetic slow waves and MEG-delta activity in
      schizophrenic patients.
AB  - BACKGROUND: Schizophrenic patients exhibit more activity in the
      electroencephalographic delta and theta frequency range than do control subjects.
      Using magnetic source imaging (MSI) our study aimed to explore this phenomenon in
      the magnetoencephalogram (MEG), the distribution of its sources, and associations
      between symptom profiles and sources of low-frequency activity in the brain.
      METHODS: Whole-head MEG recordings were obtained from 28 schizophrenic patients
      and 20 healthy control subjects during a resting condition. The generators of the
      focal magnetic slow waves were located employing a single moving dipole model.
      Distributed or multiple delta and theta sources were captured by the minimum norm
      estimate. RESULTS: Both localization procedures showed slow wave activity to be
      enhanced in schizophrenic patients compared with control subjects. Focal slow
      wave activity differed most between groups in frontotemporal and in posterior
      regions. Slow wave activity was associated with symptom characteristics in that
      positive symptoms varied with frontal delta and theta activity. CONCLUSIONS:
      Results indicate that activity in low-frequency bands in schizophrenic patients
      exceeds the activity of control subjects in distinct areas, and that this focal
      clustering of neuromagnetic slow waves may be related to psychopathologic
      characteristics.

PMID- 11526992
TI  - Modulation of glutamate receptors in response to the novel antipsychotic
      olanzapine in rats.
AB  - BACKGROUND: A disturbance in glutamate neurotransmission has been hypothesized in
      schizophrenia. Hence, the beneficial effects of pharmacological treatment may be
      related to adaptive changes taking place in this neurotransmitter system.
      METHODS: In this study, we investigated the modulation of ionotropic and
      metabotropic glutamate receptors in the rat brain following acute or chronic
      exposure to the novel antipsychotic olanzapine. RESULTS: In accordance with the
      clear distinction between classical and atypical drugs, olanzapine did not alter
      glutamate receptor expression in striatum. Chronic, not acute, exposure to
      olanzapine was capable of up-regulating hippocampal mRNA levels for GluR-B and
      GluR-C, two alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid (AMPA)
      forming subunits. This effect could be relevant for the improvement of
      schizophrenic alterations, which are thought to depend on dysfunction of the
      glutamatergic transmission within the hippocampal formation. We also found that
      the expression of group II glutamate metabotropic receptors was up-regulated in
      the frontal cortex after chronic exposure to clozapine, and to a lesser extent
      olanzapine, but not with haloperidol. CONCLUSIONS: The adaptive mechanisms taking
      place in glutamatergic transmission might prove useful in ameliorating some of
      the dysfunction observed in the brain of schizophrenic patients.

PMID- 11526993
TI  - Association between 5HT2A receptor gene promoter region polymorphism and eating
      disorders in Japanese patients.
AB  - BACKGROUND: Evidence from family and twin studies suggests a genetic contribution
      to the etiology of eating disorders (EDs). Recently, researchers have reported
      genetic associations between the MspI polymorphism (-1438A/G) of the promoter
      region of the 5HT2A receptor gene and EDs; however, reports of evidence against
      these findings make the association controversial. METHODS: The authors examined
      the prevalence of the -1438A/G polymorphism of the 5HT2A receptor gene among 182
      Japanese patients with EDs and 374 normal control subjects. Interactions of the
      association of this polymorphism with subtypes of anorexia nervosa (AN), bulimia
      nervosa (BN), and various clinical characteristics were also assessed. RESULTS:
      In contrast to previous studies reporting elevated A allele frequencies in
      patients with AN, the G allele had a significantly higher frequency in patients
      with BN but not in patients with AN, than in control subjects. Examination of the
      interactions revealed that the presence of the binge eating and/or purging
      behavior and comorbid borderline personality disorder (BPD) tended to be
      associated with increased frequency of the G allele. CONCLUSIONS: Though
      preliminary, these results can be interpreted as suggesting that the G allele of
      the 5HT2A receptor gene -1438A/G polymorphism may be associated with pathological
      features that EDs and BPD have in common, especially disinhibition in eating
      behavior and personality trait.

PMID- 11526994
TI  - EEG asymmetry: relationship to mood and risk for alcoholism in Mission Indian
      youth.
AB  - BACKGROUND: Left frontal electroencephalogram (EEG) alpha dominance has been
      hypothesized to be related to depressed mood as well as aversive motivation and
      emotion. However, few studies have prospectively evaluated electroencephalogram
      asymmetry during development in high-risk adolescents and children. METHODS: EEG
      alpha asymmetry was investigated in 134 Mission Indian children who were between
      7 and 13 years of age. The relationships between electroencephalogram alpha
      asymmetry and age, gender, parental history of alcohol dependence, Native
      American heritage, and mood/ approach behaviors were explored. RESULTS: No
      significant relationship was found between frontal alpha asymmetry and age,
      gender, or behavioral measures of depressed mood and/or approach behaviors.
      However, participants with > or = 50% Native American heritage were significantly
      more likely to have greater electroencephalogram alpha power in the left frontal
      cortex than in the right. CONCLUSIONS: The present findings suggest that the
      hypothesized relationship between EEG alpha asymmetry and measures of depressed
      mood, aversive motivation, and emotion may not be universal in all age or ethnic
      groups. Additionally, though the relationship between greater degrees of Native
      American heritage and alpha asymmetry are not as yet clear, we suggest it may be
      more related to substance abuse than depression in this population of Mission
      Indians.

PMID- 11526995
TI  - Repeated intermittent administration of psychomotor stimulant drugs alters the
      acquisition of Pavlovian approach behavior in rats: differential effects of
      cocaine, d-amphetamine and 3,4- methylenedioxymethamphetamine ("Ecstasy").
AB  - BACKGROUND: Psychomotor stimulant drugs can produce long-lasting changes in
      neurochemistry and behavior after multiple doses. In particular, neuroadaptations
      within corticolimbic brain structures that mediate incentive learning and
      motivated behavior have been demonstrated after chronic exposure to cocaine, d
      amphetamine, and 3,4-methylenedioxymethamphetamine (MDMA). As stimulus-reward
      learning is likely relevant to addictive behavior (i.e., augmented conditioned
      reward and stimulus control of behavior), we have investigated whether prior
      repeated administration of psychomotor stimulant drugs (of abuse, including
      cocaine, d-amphetamine, or MDMA, would affect the acquisition of Pavlovian
      approach behavior. METHODS: Water-deprived rats were tested for the acquisition
      of Pavlovian approach behavior after 5 days treatment with cocaine (15-20 mg/kg
      once or twice daily), d-amphetamine (2.5 mg/kg once or twice daily), or MDMA (2.5
      mg/kg twice daily) followed by a 7-day, drug-free period. RESULTS: Prior repeated
      treatment with cocaine or d-amphetamine produced a significant enhancement of
      acquisition of Pavlovian approach behavior, indicating accelerated stimulus
      reward learning, whereas MDMA administration produced increased inappropriate
      responding, indicating impulsivity. Abnormal drug-induced approach behavior was
      found to persist throughout the testing period. CONCLUSIONS: These studies
      demonstrate that psychomotor stimulant-induced sensitization can produce long
      term alterations in stimulus-reward learning and impulse control that may
      contribute to the compulsive drug taking that typifies addiction.

PMID- 11526996
TI  - Susceptibility to neuroleptic-induced tardive dyskinesia and the T102C
      polymorphism in the serotonin type 2A receptor.
AB  - BACKGROUND: Genetic factors have been implicated in the pathophysiology of the
      movement disorder tardive dyskinesia, which may involve dopamine-serotonin
      interaction. Case-control association studies have identified the T102C
      polymorphism of the 5-HT2A receptor gene as being associated with schizophrenia
      and responsiveness to clozapine. In this study, we examine the association of
      this polymorphism in the 5-HT2A receptor gene as a risk factor for developing
      schizophrenia and tardive dyskinesia from prolonged treatment with neuroleptics.
      METHODS: Ninety-seven healthy control subjects with no history of mental illness
      and 221 schizophrenic patients (87 with tardive dyskinesia, 134 without) were
      genotyped by PCR-RFLP. RESULTS: Comparison between cases and control subjects
      revealed no significant association between the C allele and schizophrenia. There
      was significant difference in allele frequency (p = .044, OR = 1.54 95% CI = 1.02
      2.33) between patients who developed tardive dyskinesia and those who did not.
      Significant difference remains even after adjusting for age and neuroleptic
      dosage (p = .041) with the odds ratio at 1.64 (95% CI = 1.02-2.62). CONCLUSIONS:
      A genetic variant of the 5-HT2A receptor may be associated with neuroleptic
      induced tardive dyskinesia in schizophrenia. Further studies are needed to
      replicate the finding. The role of 5-HT2A receptor in the etiology of tardive
      dyskinesia or treatment-resistant schizophrenia should be further investigated.

PMID- 11526997
TI  - Risperidone-associated new-onset diabetes.
AB  - BACKGROUND: Weight gain, and its associated complications such as the development
      of diabetes, is becoming increasingly recognized as an important potential side
      effect of the novel antipsychotic drugs. METHODS: Two retrospective cases are
      described in which patients with schizophrenia developed diabetes while taking
      the antipsychotic medication risperidone. RESULTS: Both patients had preexisting
      risk factors for diabetes and developed insulin resistance in the context of
      weight gain. Both cases necessitated medical intervention and one patient
      requires ongoing treatment with insulin. CONCLUSIONS: Although the exact
      mechanism of antipsychotic induced diabetes remains obscure, weight gain appears
      to be a significant risk factor. Careful monitoring of weight and fasting
      glucoses is recommended for any patient taking novel antipsychotic medications.

PMID- 11526999
TI  - Three-dimensional mapping of temporo-limbic regions and the lateral ventricles in
      schizophrenia: gender effects.
AB  - BACKGROUND: Local alterations in morphological parameters are poorly
      characterized in several brain regions widely implicated in schizophrenia
      neuropathology. METHODS: Surface-based anatomical modeling was applied to
      magnetic resonance data to obtain three-dimensional (3D) average anatomical maps
      and measures of location, shape, asymmetry, and volume for the lateral
      ventricles, hippocampus, amygdala, and superior temporal gyrus in schizophrenic
      (n = 25; 15 male) and normal subjects (n = 28; 15 male) matched for demographic
      variables. For all regions, intra-group variability was visualized and group
      differences assessed statistically to discriminate local alterations in anatomy
      across sex and diagnosis. RESULTS: Posterior hippocampal volumes, lengths, and
      widths were reduced in patients. The right amygdala showed volume increases in
      schizophrenia patients versus controls. Ventricular enlargements, pronounced in
      the left hemisphere, occurred in the superior and lateral dimensions in patients,
      and these effects interacted with gender. Superior horn anterior extremes,
      inferior horn volumes, and hippocampal asymmetries exhibited gender effects.
      Significant group differences were absent in superior temporal gyrus parameters.
      Finally, regional variability profiles differed across groups. CONCLUSIONS: Clear
      morphometric differences of the lateral ventricles, hippocampus, and amygdala
      indicate regional displacements and shape distortions in several functional
      systems in schizophrenia. Alterations in these structures as mapped in 3D may
      provide the foundation for establishing brain abnormalities not previously
      defined at such a local level.

PMID- 11527000
TI  - Relative risk for cognitive impairments in siblings of patients with
      schizophrenia.
AB  - BACKGROUND: Patients with schizophrenia have impairments in several domains of
      cognition, including working memory/executive function, verbal memory, language,
      oculomotor scanning/psychomotor speed, and general intelligence. Impairments have
      also been found in unaffected siblings, suggesting they could be heritable. To
      assess the suitability of cognitive dysfunction for use in genetic studies, we
      estimated relative risk (lambda) in a large cohort of siblings. METHODS: One
      hundred forty-seven patients with schizophrenia, 193 of their siblings, and 47
      control subjects were studied using a neuropsychological test battery, which
      included intelligence quotient (IQ), Wide Range Achievement Test, Wisconsin Card
      Sort, Wechsler Memory Scale (revised), California Verbal List Test, Trails A and
      B, and Letter and Category Fluency. Relative risk was estimated using a cutoff
      score of 1 SD below the control mean. RESULTS: As expected, patients performed
      markedly worse than control subjects on all tests except the Wide Range
      Achievement Test. Siblings had impaired performance on the Wisconsin Card Sort
      and Trails B, with trends for reduction (p = .01-.05) on the California Verbal
      List Test and Letter Fluency. Relative risk to siblings was elevated on the
      Trails B (lambda = 4.0) and California Verbal List Test (lambda = 2.8). Trends (p
      = .01-.05) for increased lambda were also seen for Wisconsin Card Sort, Letter
      Fluency, Wechsler Memory Scale and decline in IQ (lambda = 1.74-2.4).
      Correlations between tests of different cognitive functions were weak, indicating
      they measure relatively independent processes. CONCLUSION: Unselected siblings of
      patients with schizophrenia have impairments in several cognitive domains.
      Relative risk scores were in the moderate range, suggesting a significant genetic
      component. Impairments on one test only weakly predicted impairments on other
      tests. Thus, cognitive phenotypes identify distinct, familial traits associated
      with schizophrenia. Using this dimensional approach to subdividing schizophrenia
      may reduce the clinical and genetic heterogeneity of schizophrenia and improve
      the power of genetic studies.

PMID- 11527001
TI  - The therapeutic potential of 5-HT6 receptor antagonists.

PMID- 11527002
TI  - Cost effectiveness of the newer atypical antipsychotics: a review of the
      pharmacoeconomic research evidence.
AB  - A comprehensive evaluation of atypical antipsychotics for the treatment of
      schizophrenia involves documentation of clinical effectiveness, quality of life
      and medical cost outcomes. The results of pharmacoeconomic studies assist
      psychiatrists, and other healthcare decision-makers, in identifying
      pharmacotherapies that provide the greatest benefit to patients at the most
      acceptable cost. The cost-effectiveness of the newer atypical antipsychotics has
      been examined using clinical decision-modeling studies and randomized clinical
      trials. The research evidence suggests that clozapine is a cost-effective
      treatment for neuroleptic refractory schizophrenia. Olanzapine and risperidone
      may be cost-neutral or, at best, slightly cost-saving compared with conventional
      antipsychotics, although they do improve clinical symptoms and quality of life
      outcomes. There is insufficient published data on pharmacoeconomic outcomes for
      sertindole, quetiapine and ziprasidone to make any conclusions about their cost
      effectiveness in treating schizophrenia.

PMID- 11527003
TI  - SB-271046 (SmithKline Beecham).
AB  - SmithKline Beecham is developing the 5-HT6 antagonist, SB-271046, as a potential
      cognition enhancer. By December 1999, phase I trials had commenced [360354]. This
      drug was originally being developed primarily for the treatment of shizophrenia
      [284490], however, cognitive disorders, including but not limited to Alzheimer's
      disease, have been the main target since 1998 [394309]. SB-271046 is a potent,
      selective 5-HT6 antagonist with a pKi value of 8.9 [333710]. SB-258585, also
      known as 4-iodo-N-[4-methoxy-3-(4-methylpiperazin-1-yl)phenyl]benzenesulfonamide
      is an analog of SB-271046 [322488]. Data recently presented at the Society for
      Neuroscience annual meeting in November 2000 demonstrated that administration of
      SB-271046 resulted in a signficant increase in glutamate and aspartate levels in
      the frontal cortex, without affecting noradrenaline, dopamine or 5-HT levels.
      This was stated to suggest that 5-HT6 antagonists might therefore be useful for
      treating cognitive dysfunction [390469]. The drug has also been radiolabeled in
      order to provide an assay for estimating in vivo 5-HT6 receptor occupancy
      [390470].

PMID- 11526998
TI  - A neurobiological basis for substance abuse comorbidity in schizophrenia.
AB  - It is commonly held that substance use comorbidity in schizophrenia represents
      self-medication, an attempt by patients to alleviate adverse positive and
      negative symptoms, cognitive impairment, or medication side effects. However,
      recent advances suggest that increased vulnerability to addictive behavior may
      reflect the impact of the neuropathology of schizophrenia on the neural circuitry
      mediating drug reward and reinforcement. We hypothesize that abnormalities in the
      hippocampal formation and frontal cortex facilitate the positive reinforcing
      effects of drug reward and reduce inhibitory control over drug-seeking behavior.
      In this model, disturbances in drug reward are mediated, in part, by dysregulated
      neural integration of dopamine and glutamate signaling in the nucleus accumbens
      resulting form frontal cortical and hippocampal dysfunction. Altered integration
      of these signals would produce neural and motivational changes similar to long
      term substance abuse but without the necessity of prior drug exposure. Thus,
      schizophrenic patients may have a predilection for addictive behavior as a
      primary disease symptom in parallel to, and in many, cases independent from,
      their other symptoms.

PMID- 11527004
TI  - M-100907 (Aventis).
AB  - M-100907 is a highly selective 5-HT2A antagonist that is being developed by
      Aventis Pharmaceuticals, formerly Hoechst Marion Roussel (HMR), for the potential
      treatment of schizophrenia. M-100907 is in phase III trials for chronic
      schizophrenia [307936], [307942], [307940]. In August 1999, development was
      discontinued for acute schizophrenia (schizoaffective disorder) on the basis of
      poor results [335083]. M-100907 is a potent antagonist in every putative animal
      behavioral model of schizophrenia that involves activation of 5-HT2A receptors
      [181713]. Interestingly, M-100907 is also active in animal models involving
      blockade of NMDA glutamatergic channel receptors, an effect known to resemble
      some behavioral symptoms of schizophrenia in man [390328]. M-100907 belongs to a
      series of piperidine derivatives, which were originally disclosed in the
      associated patent, EP-00208235. M-100907 is specifically claimed in a later
      patent, EP-00531410. This patent describes superior in vivo potency for M-100907
      and its claims include the use of M-100907 for the treatment of thromboembolic
      disorders. The use of M-100907 for the treatment of various developmental
      neurological disorders such as autism and attention deficit hyperactivity
      disorder is disclosed in WO-09956750. In 1996, this product was designated one of
      HMR's nine top priority products, serving an unmet medical need and addressing a
      potential market in excess of US $500 million per year [221118]. In January 1999,
      BT Alex Brown predicted sales of US $30 million in 2000 rising to US $220 million
      in 2002 [318220]. In April 1999, ABN Amro predicted annual sales of DM 50 million
      in 2000, rising to DM 150 million in 2002 [328676].

PMID- 11527005
TI  - Humoral and cellular immune responses: independent forces or collaborators in the
      fight against cancer?
AB  - Recent advances in our understanding of immune function with regard to the
      generation of a potent antitumor response have resulted in a renewed interest in
      cancer vaccines and point to a role for immunotherapy in the treatment of cancer.
      Currently, the majority of vaccine strategies for the treatment of solid
      malignancies focus on the generation of cytotoxic T lymphocytes (CTL) that
      destroy tumor cells that express a given target protein, or antigen. However,
      antibody therapies have already been successful against some cancers. Current
      humoral immunotherapy typically involves the passive infusion of monoclonal
      antibodies, which usually target a specific tumor-encoded antigen. However,
      vaccines can be engineered to induce humoral immunity. By focusing on the
      cellular arm of the immune response at the expense of humoral immunity (or the
      converse), we may have inadvertently limited the potential efficacy of our
      anticancer vaccines. This article seeks to explore the notion that a vaccine
      designed to optimally activate both arms of the immune system may well generate
      an antitumor immune response greater than the sum of the two individual effector
      mechanisms alone.

PMID- 11527007
TI  - Alemtuzumab (Millennium/ILEX).
AB  - Alemtuzumab, a lymphocyte-depleting humanized monoclonal antibody, is being
      developed by Millennium Pharmaceuticals Inc and ILEX Oncology for the potential
      treatment of chronic lymphocytic leukemia (CLL) [274580]. The utility of the
      compound for treating bone marrow (BM) stem cell transplantation-associated graft
      versus-host disease (GVHD) [372946] and for ex vivo purging of BM to remove
      malignant T-cells [244056] is also being investigated. Additional potential
      therapeutic areas for which clinical trials are planned or ongoing include
      vasculitis, multiple sclerosis [288762] and organ transplantation [338304]. A
      Biologics License Application (BLA) was filed with the FDA in December 1999 by
      ILEX and Millennium [351523], [351524], [373873]. The FDA accepted the
      application for filing in February 2000 [355775] and returned a complete response
      letter in June 2000 [372172]. Millennium and ILEX submitted a response to the FDA
      in August 2000 [379766]. Alemtuzumab has received Fast Track designation [304771]
      and orphan drug status from the FDA [288762], and the drug was reviewed by the
      FDA's Oncologic Drugs Advisory Committee on 14 December, 2000 [387228]. The
      committee voted 14 to 1 to recommend accelerated approval of alemtuzumab for
      patients with CLL who have been treated with alkylating agents and who have
      failed fludarabine therapy [393778], [393894]. In March 2000, Millennium and ILEX
      also submitted a Marketing Authorization Application (MAA) for alemtuzumab to the
      European Agency for the Evaluation of Medicinal Products (EMEA) [363595]. In
      October 2000, EMEA accepted the MAA for alemtuzumab under the agency's
      centralized approval procedure [387228]. Alemtuzumab was originally synthesized
      by Herman Waldmann and colleagues at Cambridge University and licensed to
      Burroughs Wellcome (BW) via the British Technology Group (BTG) [162622]. BW
      conducted phase I and II trials for a broad range of indications, but then
      discontinued development because of disappointing results in phase II rheumatoid
      arthritis trials [326848]. In April 1997, LeukoSite licensed rights to the
      antibody from BTG for the treatment of CLL and prolymphocytic leukemia, plus an
      option to develop it for other indications. BW agreed to supply LeukoSite with
      intellectual property [244056], [326848]. In May 1997, LeukoSite entered into a
      joint venture with ILEX Oncology for the further development of alemtuzumab
      [245986]. By the end of 1999, Millennium acquired LeukoSite with commitment to
      pursue development of the compound through the joint venture Millennium & ILEX
      Partners LP [351523], [370237]. In August 1999, Schering AG and its US affiliate
      Berlex Laboratories obtained exclusive worldwide marketing rights for
      alemtuzumab, excluding Japan and East Asia. In the US, Berlex, Millennium and
      ILEX will divide profits from alemtuzumab sales equally [337702], [338837].

PMID- 11527006
TI  - Endothelial monocyte activating polypeptide II (EMAP II) enhances the effect of
      TNF on tumor-associated vasculature.
AB  - Endothelial monocyte activating polypeptide II (EMAP II) was initially identified
      as a factor that may modulate the interaction of tumor necrosis factor (TNF) with
      tumor vascular endothelium. Since the toxicity of TNF has continued to hamper its
      clinical use in cancer patients, investigators have developed a renewed interest
      in modulators such as EMAP II. Over a period of 25 years, investigations into the
      mechanism of antitumor action of TNF have yielded important observations
      concerning the role of the microvasculature as the target for TNF's activity.
      EMAP II was identified as an endothelial response mediator secreted by a highly
      TNF-sensitive tumor line, the Meth A fibrosarcoma. When used to treat tumors,
      either by systemic administration of recombinant protein or by gene transfer,
      EMAP II upregulates cellular receptors for TNF on endothelial cells and confers
      TNF sensitivity to tumors previously believed to be TNF-resistant. Potential
      mechanisms for EMAP II's selective effects on endothelial cells have been
      described. These include induction of endothelial cell apoptosis and upregulation
      of TNF receptor I (TNFR1). Other recent investigations have posited various
      physiological roles for EMAP II, ranging from the mediation of inflammation to
      the vascular remodeling that occurs during normal embryogenesis. EMAP II has
      generated interest as a modulator of TNF response for isolated whole-organ,
      isolated limb, or systemic perfusion. By enhancing the tumor vasculature response
      to TNF, EMAP II may enable lower, non-toxic doses of TNF to be used to clinical
      advantage.

PMID- 11527009
TI  - Towards the development of vaccines against Helicobacter pylori: status and
      issues.
AB  - Helicobacter pylori is one of the most common bacteria worldwide. It infects more
      than 50% of the human population, and causes serious gastric diseases, such as
      chronic gastritis, peptic ulcer and, in some individuals, gastric cancer. The
      current treatment with antibiotics is not without drawbacks. The development of
      vaccines could help enormously in reducing the burden of H. pylori-associated
      diseases. A large body of evidence from experimental animal models has shown that
      vaccine-mediated prevention or vaccine-induced eradication of H. pylori is
      feasible. Several issues, however, are still unresolved, concerning the quality
      of the induced immune response necessary to achieve strong and sustained
      protective immunity in man. Several trials in humans are planned for the next few
      years. These studies will tell whether vaccination against H. pylori is feasible
      in man, and will offer the great opportunity to understand better the
      relationship between this ancient bacterium and humans.

PMID- 11527008
TI  - The use of CpG DNA as a mucosal vaccine adjuvant.
AB  - CpG DNA has been shown to be a potent adjuvant in many disease models. Most
      studies using CpG DNA as adjuvant have used parenteral delivery, but more
      effective protection against mucosal pathogens could be achieved with effective
      mucosal immunization. Recently, mucosal immunization with CpG DNA as an adjuvant
      has been shown to induce both systemic (humoral and cellular) and mucosal antigen
      specific immune responses. This review will concentrate on the use of CpG DNA as
      an adjuvant for the induction of mucosal immunity.

PMID- 11527010
TI  - Vaccines: ideal drugs for the 21st century?

PMID- 11527011
TI  - Menjugate (Chiron).
AB  - Chiron has developed and launched Menjugate, a vaccine for the treatment for
      meningococcus C infections caused by the pathogen Neisseria meningitidis
      [177064]. In August 1999, Chiron filed with the UK MCA for a license to market
      Menjugate. The licence was granted in March 2000 [339082], [344773], [357897] and
      as of April 2000, a vaccination program was underway in the UK [362152].
      Menjugate is indicated for children of 12 months and older, but Chiron was
      expecting approval in the US for infants younger than 12 months by the end of
      2000. The company will also pursue mutual recognition in Europe [376204]. In
      August 2000, Chiron received marketing clearance for Menjugate from the Irish
      Medicines Board as a conjugate against meningococcal C disease [378353]. The
      vaccine employs CRM-conjugate technology, whereby a diphtheria toxoid is used as
      a carrier protein for the meningitis C-specific antigens. The vaccine is being
      developed for its potential to provide protection against meningitis in both
      adults and infants. In July 2000, Chiron entered into a comarketing and co
      promotion agreement with Aventis Pasteur under which Aventis will assist Chiron
      in marketing and sales efforts for Menjugate in the UK [374760].

PMID- 11527012
TI  - Tetracel (American Home Products).
AB  - American Home Products (AHP) is developing Tetracel as a vaccine for children
      (aged 12 to 18 months) against diphtheria, tetanus, pertussis and Haemophilus
      influenzae type B (Hib) [275146]. The components are contained in AHP's two
      currently marketed vaccines. ACEL-Immune contains diphtheria and tetanus toxoids
      with acellular pertussis vaccine adsorbed, and HibTITER contains the Haemophilus
      influenzae B conjugate vaccine (diphtheria CRM197 protein conjugate) [239655]. As
      of January 2000, Lehman Brothers predicted Tetracel to be approved in the US
      during 2000 [354434].

PMID- 11527013
TI  - Inhaled anticholinergic therapy: applied pharmacology and interesting
      developments.

PMID- 11527014
TI  - Neutrophil-derived elastases and their inhibitors: potential role in the
      pathogenesis of lung disease.
AB  - The proteinase-antiproteinase hypothesis still receives support from clinical and
      experimental observations in a range of inflammatory lung diseases. The function
      of these molecules appears to be broader than originally believed and further
      research is likely to lead to an improved understanding of their role in the
      regulation of both the beneficial and detrimental effects in inflammatory
      response and the maintenance of the homeostasis in the normal lung. Thus the
      potential for the development as therapeutic tools is likely to become more
      attractive as improved drug development and delivery mechanisms appear.

PMID- 11527015
TI  - ABT-761 (Abbott).
AB  - Abbott's ABT-761 is a 5-lipoxygenase inhibitor with 8-fold increased potency over
      Bay-X-1005 and 150-fold over zileuton [171665]. It has a longer duration of
      action than its closest competitor, ZD-2138 (AstraZeneca), and has entered phase
      III trials for asthma [224216]. ABT-761 is the follow-up compound for zileuton
      and, due to its increased potency, requires only once-daily dosing [187700]. ABT
      761 has shown excellent oral bioavailability and an extended duration of plasma
      levels in man, and initial results for a single 200 mg po dose have shown a
      significant protective effect against exercise- and adenosine-induced
      bronchoconstriction in asthmatics [215839]. The drug is well tolerated in healthy
      volunteers and shows linear pharmacokinetics. The pharmacokinetics in children
      are similar to that of adults.

PMID- 11527016
TI  - Inhibition of cardiac ATP-dependent potassium channels by sulfonylurea drugs.

PMID- 11527017
TI  - Therapy of heart failure.

PMID- 11527018
TI  - New antiarrhythmic agents for atrial fibrillation.

PMID- 11527019
TI  - KCB-328 (C&C Research Labs).
AB  - C & C Research Labs is investigating the class III antiarrhythmic KCB-328 as a
      potential treatment for heart arrhythmia [310688]. The compound is potent in
      vitro, with little reverse frequency-dependence when compared with E-4031 (qv)
      and dofetilide (qv) [223384]. KCB-328 is in preclinical development [351687].

PMID- 11527020
TI  - Tedisamil (Solvay).
AB  - Tedisamil, a potassium channel blocker (class III anti-arrhythmic agent)from
      Solvay, is in phase II trials for the potential treatment of atrial fibrillation
      [342434]. The drug had completed phase III trials for angina pectoris [342434],
      [177648], and although an NDA dossier for angina pectoris in refractory patients
      was ready for filing with the US FDA, Solvay has decided to pursue the broader
      indication of atrial fibrillation instead [342434]. Tedisamil is bradycardic
      without producing a negative inotropic effect. In a canine model of exercise
      induced angina, myocardial function was maintained. In rat, rabbit, canine and
      simian hearts, there was a marked prolongation of action potential, due to
      tedisamil's modulating effects on potassium channels. Diastolic arterial pressure
      was not influenced [276934]. Tedisamil also rapidly terminated sustained atrial
      fibrillation and prevented its reinitiation in a canine model of the condition
      [315378]. The class III antiarrhythmic effect of tedisamil is related
      predominantly to the strong blocking effect of the drug on the rapid component of
      the delayed rectifier potassium current [334806].

PMID- 11527021
TI  - Arbor marking.

PMID- 11527022
TI  - Flexor digitorum longus transfer and medial displacement calcaneal osteotomy for
      posterior tibial tendon dysfunction: a middle-term clinical follow-up.
AB  - HYPOTHESES/PURPOSE: The medial displacement calcaneal osteotomy has recently
      become a popular addition to flexor digitorum longus transfer for stage II
      posterior tibial tendon dysfunction. We reviewed the results of 26 patients who
      had undergone the procedure at an average of 32 months prior to follow-up (range
      12 to 70 months) with particular attention to objective functional parameters.
      CONCLUSIONS/SIGNIFICANCE: FDL transfer and medial displacement calcaneal
      osteotomy provides good functional and symptomatic results in the middle-term.
      The operation preserves the majority of subtalar motion and is objectively
      durable as assessed by the continued ability to perform a single-leg toe rise.
      Although moderate radiographic improvement in the arch is frequent, often
      patients fail to notice this clinically. A prolonged period of steady improvement
      in symptoms after surgery is common. SUMMARY OF METHODS/RESULTS: Between 1993 and
      1998, 26 patients underwent flexor digitorum longus transfer and medial
      displacement calcaneal osteotomy performed by the senior author. Sixteen returned
      for the study and were seen for physical exams. Three were included on the basis
      of chart review including one who was deceased and two who could not be
      contacted. Five further patients included on the basis of chart review were also
      contacted for telephone interviews. For the survival analysis, however, their
      last physical examination was used as the follow-up date. Two patients who had
      early technical failures were not interviewed but were counted as early failures
      of the procedure in the survival analysis. Functionally, all patients except
      three could perform a single-leg toe rise at follow-up, a maneuver none could
      perform preoperatively. Of these three, two cases were technical failures with
      loss of fixation of the FDL transfer early in the postoperative course,
      ultimately requiring revision procedures including one subtalar fusion. Another
      patient was a late failure after developing increasing pain and weakness during a
      pregnancy 69 months after the procedure. Clinically assessed subtalar motion
      remained 81 +/- 15% of the contralateral side in those patients with unilateral
      disease. Although improvement in the radiographic alignment of the foot was
      commonly noted, only 50% of patients felt the conformation of their foot had
      noticeably changed, and only one (4%) felt the improvement to be significant.
      Pain relief was rated excellent by 75% and good by 16%; the average AOFAS
      Hindfoot pain subscale score was 35.2 (out of 40 possible). Function was felt to
      be markedly improved by all patients except the three who were unable to perform
      a single-leg toe rise. The average score for the four functional symptom
      categories of the AOFAS score was 26.8 (out of 28 possible). Most patients noted
      that although they were able to perform daily activities after their
      postoperative immobilization was liberalized, there was a prolonged period of
      steady improvement in symptoms and function after surgery. The median length of
      time to self-rated maximal medical improvement was 10 months.

PMID- 11527023
TI  - Isolated talonavicular arthrodesis for talonavicular arthritis.
AB  - We have reviewed a single surgeon's experience with isolated talonavicular fusion
      in 16 patients with talonavicular arthritis. Fixation was either by staples or
      screws. Fifteen solid unions were achieved in the 16 patients who were followed
      (mean: 51 months). The average Ankle-Hindfoot Scale improved from 77.2
      preoperatively to 92.9 postoperatively (p < 0.001). Subjectively, 15 patients
      were satisfied and one patient dissatisfied with the results. Further
      osteoarthritis in the adjacent joints was noted in five patients. We concluded
      that isolated talonavicular fusion is an effective method of treatment of
      talonavicular arthritis regarding pain relief and functional improvement. Though
      osteoarthritis was found in some adjacent joints postoperatively, the results
      were still satisfactory.

PMID- 11527024
TI  - Ligamentous restraints of the second tarsometatarsal joint: a biomechanical
      evaluation.
AB  - Ligamentous injury of the tarsometatarsal joint complex is an uncommon, but
      disabling condition that frequently occurs in elite athletes. There are few
      options for managing these injuries, in part because the relative mechanical
      contribution of the ligaments of the tarsometatarsal joint is unknown,
      complicating decisions regarding which ligaments need reconstruction. In the
      current study, strength and stiffness of the dorsal, plantar, and Lisfranc
      ligaments of 20 paired cadaver feet were measured and compared. The plantar and
      Lisfranc ligaments were significantly stiffer and stronger than the dorsal
      ligament, and the Lisfranc ligament was significantly stronger and stiffer than
      the plantar ligament.

PMID- 11527025
TI  - The influence of perioperative soft tissue complications on the clinical outcome
      in surgically treated ankle fractures.
AB  - The influence of perioperative soft tissue complications on the functional
      outcome after open reduction and internal fixation of closed ankle fractures was
      investigated. Eighty-eight consecutive patients were followed 3.7 years (SD +/-
      0.6) after the injury. Two major and 21 minor soft tissue complications were
      registered. Average dorsal extension was 29.9 degrees (range four to 54, SD +/-
      9.5) of the fractured ankles and 37.2 degrees (range eight to 60, SD +/- 9.1) of
      the non-fractured ankles. The average subjective functional score was 84.6 (range
      40 to 100, SD +/- 14.9). A significant difference was found with respect to the
      subjective functional score (p = 0.048, Kruskal-Wallis test) but not with respect
      to dorsal extension (0.358, Kruskal-Wallis test) when comparing groups of minor,
      major and no soft tissue complications. This study suggests that major soft
      tissue complications have a negative effect on the long-term functional outcome
      after surgical repair of an ankle fracture. Minor soft tissue complications,
      primary skin problems, the timing of primary surgery and fracture types according
      to AO/ASIF have no or minor influence on the long-term functional result. This
      study confirms previous reports that the presence of osteoarthritis is frequently
      associated with a reduced functional outcome.

PMID- 11527026
TI  - Foot and ankle injuries in motor vehicle accidents.
AB  - BACKGROUND: We studied foot and ankle (F/A) injuries that occurred in motor
      vehicle accidents treated in a Level 1 trauma center. METHODS: The records of F/A
      injuries of 2248 consecutive orthopedic patients were reviewed to find foot and
      ankle injuries. RESULTS: Pilon fractures were common. Motor Vehicle Accident
      (MVA) occupants with F/A injuries had a higher injury Severity Score than those
      without (17.9 vs. 11.6, p <. 001). MVA F/A injury risk was higher without
      restraint [relative risk ratio (rrr) 1.68, p <. 0032] than with restraint except
      for air bagged drivers who were similar to unrestrained drivers (rrr 1.18, p >
      .05, NS). CONCLUSION: Patients with F/A injuries may have serious associated
      injuries. Air bags may not protect feet.

PMID- 11527027
TI  - Ground reaction forces at discrete sites of the foot derived from pressure plate
      measurements.
AB  - While the literature is replete with studies investigating the pressure beneath
      the human foot during walking, ground reaction forces experienced at discrete
      sites may provide a more valuable insight into its mechanical behavior during
      gait. Despite the fact that changes in the distribution of force have been
      reported to occur with both foot deformity and fatigue, site-specific force data
      for nonpathological gait is not well documented. The current study provides an
      indirect estimate of force and accompanying temporal parameters, for discrete
      sites of the foot in young, healthy adults walking at their preferred speed.

PMID- 11527028
TI  - The relationship of the heel pad compressibility and plantar pressure
      distribution.
AB  - Loss of heel pad elasticity has been suggested as one of the possible
      explanations of heel pain. This study aimed to determine the effect of heel pad
      thickness and its compressibility to heel pressure distribution, in 47 (94 feet)
      normal subjects and 59 (94 feet) patients with heel pain, using radiological
      measurements and EMED-SF (Novel, Munich) plantar pressure distribution
      measurement system. Both heels of the patients and control group were
      radiographed with and without weight bearing. The ratio of the heel pad thickness
      in loading to unloading position was defined as "the heel pad compressibility
      index." The plantar peak pressure of the heel was measured at heel strike phase
      of the gait cycle. The compressibility index for control and patient groups were
      found to be 0.60 and 0.69, respectively. The peak pressure under the heel pad was
      recorded to be 28.4 N/cm2 for patients and 31.7 N/cm2 for control group. No
      significant difference was found for heel pad compressibility index and heel pad
      pressures between patient and control groups (p > 0.05). This study revealed that
      there is no relationship between heel pad compressibility and pressure
      distribution of the heel pad both in control and patient group. We feel the
      flexibility of the heel pad does not have any influence on heel pain syndromes.

PMID- 11527029
TI  - Outcome of ankle arthrodesis performed by dowel technique in patients with
      rheumatic disease.
AB  - Between the years 1988 and 1994, 19 ankle arthrodeses were performed on 18
      patients (nine men) using the dowel technique. Patients were followed until a
      fusion had occurred, a non-union was successfully rearthrodesed, or a
      pseudoarthrosis was stabilized with orthosis treatment. Patients' radiographs and
      documents were analyzed both preoperatively and during the healing period.
      Subtalar fusion had been performed previously in eight ankles and rheumatoid
      destruction of subtalar complex was observed in seven other hindfeet. The
      original dowel method was used in 13 ankles and a modified procedure was
      performed in six. Local bone grafts were utilized. Solid fusion was achieved in
      13 ankles (68%), but with delayed union in two cases. Non-union was present in
      six ankles, and two re-arthrodeses were performed with successful fusion in the
      other. Orthosis treatment was necessary in three of five ankles with permanent
      non-union. One chronic infection leading to non-union was detected. Only two of
      the six ankles (33%) with the modified technique using additional exposures
      healed without complications. In the dowel technique, the preoperative position
      of the ankle and location of the guiding Kirschner wire are of crucial importance
      and the original technique with a large cutter should be used. In patients with
      rheumatic disease, this fusion method did not yield acceptable results.

PMID- 11527030
TI  - Angioleiomyoma: clinical presentation and surgical management.
AB  - Angioleiomyomas are relatively rare, benign, vascular soft tissue tumors with a
      predilection for the lower extremity. They may occur in either the cutaneous or
      subcutaneous tissue and are usually well encapsulated. Erosion of adjacent bone
      due to secondary compression phenomenon has rarely been reported in the
      literature. This study describes three cases.

PMID- 11527032
TI  - Osteoarticular tuberculosis of the foot and ankle.

PMID- 11527031
TI  - Basal cell carcinoma of the nail unit: a case report.
AB  - Basal cell carcinomas (BCC) of the foot are rare. A review of the English
      literature found only 23 cases of BCC reported in the foot, none of which
      involved the nail unit. The nail unit, which is composed of the nail bed and nail
      folds, is an exceedingly atypical site for basal cell carcinomas. A case of BCC
      of the proximal nail fold of the hallux which was treated with Mohs Micrographic
      Surgery (MMS) is presented.

PMID- 11527033
TI  - Technique tip: Revisiting an alternative method of fixation for first MTP joint
      arthrodesis.

PMID- 11527034
TI  - The use of psychophysical tuning curves to explore dead regions in the cochlea.
AB  - OBJECTIVE: "Dead regions" are regions in the cochlea with no functioning inner
      hair cells (IHCs) and/or neurons. Amplification (using a hearing aid) over a
      frequency range corresponding to a dead region may not be beneficial and may even
      impair speech intelligibility. The objective of this article is to illustrate the
      use of psychophysical tuning curves (PTCs) as a tool for investigating dead
      regions and to illustrate the variety of audiogram configurations that can be
      associated with dead regions. We explore the influence of signal level and signal
      frequency to test the hypothesis that the frequency at the tip of the tuning
      curve defines the boundary of the dead region. DESIGN: PTCs were measured for
      five subjects with sensorineural hearing loss who were suspected of having dead
      regions. One had a relatively "flat" loss, one had a mild mid-frequency loss and
      three had high-frequency losses, varying in severity from 70 dB to more than 120
      dB. For each PTC, the level and frequency of the sinusoidal signal were fixed,
      and the level of a narrowband noise masker needed just to mask the signal was
      determined as a function of the masker frequency. When the signal falls in a
      frequency region that is not "dead," the signal is detected via IHCs with
      characteristic frequencies (CFs) at or close to the signal frequency. In such a
      case, the tip of the PTC (the masker frequency at which the masker level is
      lowest) lies at or close to the signal frequency. When a dead region is present,
      the signal is detected via IHCs with CFs different from that of the signal
      frequency. In such a case, the tip of the PTC is shifted away from the signal
      frequency. RESULTS: PTCs with frequency-shifted tips (indicative of dead regions)
      were found for all subjects. The frequencies at the tips sometimes decreased
      slightly with increasing signal level. For the subject with a relatively flat
      loss, PTCs with tips close to 3000 Hz were obtained for signal frequencies of
      400, 1000 and 1500 Hz. A PTC with a tip at 5000 Hz was found for a signal
      frequency of 6000 Hz. These results suggest that this subject had an "island" of
      surviving IHCs and neurons with CFs ranging from 3000 to 5000 Hz, with extensive
      dead regions on either side. For the subject with a mid-frequency loss, the
      pattern of results suggested a mid-frequency dead region. For the subjects with
      high-frequency loss, the results suggested the presence of high-frequency dead
      regions, in one case starting at a frequency where absolute thresholds were only
      slightly higher than normal. CONCLUSIONS: PTCs can be used to detect and delimit
      dead regions. Often, the frequency at the tip of the PTC can be used to define
      approximately one boundary of the dead region. However, the detection of beats
      can affect the shape of the PTC around the tip when the signal frequency lies
      just inside the dead region. The level of the signal can also have some effect on
      the frequency at the tip of the PTC. Very low signal levels can lead to variable
      results. Dead regions can start at frequencies where absolute thresholds are near
      normal.

PMID- 11527035
TI  - Audiologic aspects of the search for DFNA20: a gene causing late-onset,
      progressive, sensorineural hearing loss.
AB  - OBJECTIVE: The purpose of this research was to identify the gene responsible for
      a novel form of nonsyndromic, late-onset, bilateral, progressive, sensorineural
      hearing loss in a Michigan family of English descent. This report describes the
      audiologic aspects of the search. DESIGN: Fifty-eight members of the family
      served as subjects for the study. Family pedigree information was gathered from
      family interviews, family records, birth and death registration records and
      census data. Audiologic evaluation was used to describe the hearing loss
      (phenotype) and classify family members as affected or unaffected based on
      hearing status. These data then were used in a linkage analysis, a process in
      which the inheritance of a trait is compared with the inheritance of genetic
      markers and statistically significant associations are sought. RESULTS: The team
      mapped the hearing loss to the long arm of chromosome 17 at band 17q25. The
      pattern of inheritance is autosomal dominant. The search for the gene is
      continuing using a candidate gene approach. CONCLUSIONS: The hearing loss
      demonstrated by this mid-Michigan family is a novel form of nonsyndromic,
      genetic, late-onset, bilateral, progressive, sensorineural hearing loss. The
      locus of the gene, the 20th for autosomal dominant hearing loss, is at band 17q25
      of chromosome 17.

PMID- 11527036
TI  - Estimation of psychophysical levels using the electrically evoked compound action
      potential measured with the neural response telemetry capabilities of Cochlear
      Corporation's CI24M device.
AB  - OBJECTIVE: The goal of this study was to estimate psychophysical levels using the
      electrically evoked compound action potential (EAP), measured with the Neural
      Response Telemetry capabilities of Cochlear Corporation's Nucleus CI24M cochlear
      implant system. DESIGN: Twelve postlingually deafened adults with at least 3 mo
      of implant experience with the CI24M were subjects in this study. EAP growth
      functions were successfully quantified on each active electrode of every subject.
      Correlation and regression analyses were performed between EAP measures and
      cochlear implant fitting psychophysics. Other information including performance,
      etiology and duration of hearing loss, and individual electrode impedance was
      considered. RESULTS: EAP thresholds were found to be highly correlated with
      psychophysical thresholds. The rate of EAP growth with increasing stimulation
      levels was also found to be correlated with the dynamic range of loudness limits
      and psychophysical thresholds in some subjects. No relationship was evident
      between EAP measures and speech perception tests. CONCLUSIONS: Information from
      EAP growth function measurements may be used to estimate psychophysical
      information used in cochlear implant fitting but not to predict performance with
      the device.

PMID- 11527037
TI  - Three-dimensional spiraling finite element model of the electrically stimulated
      cochlea.
AB  - OBJECTIVE: The objective of the article is to provide an accurate model of the
      human cochlea with which potential distributions and thus neural excitation
      patterns around cochlear implant electrodes can be determined. Improvements on
      previous models of the implanted cochlea are that this model 1) includes the
      spiral nature of the cochlea as well as many other anatomical details (and it is
      a model of the human cochlear rather than the guinea pig cochlea), and 2)
      facilitates modeling of different electrode geometries, array locations and
      electrode separations without changing the structure of the model. DESIGN: A
      three-dimensional spiraling finite element model of the human cochlea was
      created. The model incorporates the effect of neighboring canals and conduction
      along the fluid-filled canals of the cochlea. Potential distributions are used as
      inputs to a nerve fiber model to investigate auditory nerve excitation patterns
      around intracochlear electrode arrays. RESULTS: Potential distributions around
      intracochlear electrodes generated with the finite element model are presented.
      The effects of electrode separation, electrode geometry and array location on
      excitation threshold, excitation spread and ectopic excitation (i.e., excitation
      of nerve fibers at an undesirable location) are demonstrated. CONCLUSIONS: The
      following conclusions should be considered preliminary, as their accuracy depends
      on the exactness of the underlying model. The spiraling geometry of the cochlea
      causes asymmetry in potential distributions. The location of electrodes along the
      length of the basilar membrane has a stronger influence on the site of excitation
      than the polarity of the leading phase of the stimulus. Array location is the
      primary parameter that controls excitation spread. Threshold currents and the
      effect of ongoing loss of peripheral dendrites on threshold currents can be
      limited by placing arrays close to the modiolus. Point electrode geometries are
      recommended above banded electrode geometries only when the array can be placed
      close to the modiolus. There is a tradeoff between array location and the degree
      of ectopic stimulation caused by a specific array location. Bimodal excitation
      patterns exist at comfortable stimulus intensities for longitudinal bipolar
      electrode configurations. It is shown that an electrode configuration with an
      electrode separation of approximately half that of the bipolar electrode
      separation of the Nucleus electrode can be used instead of radial and offset
      radial electrode configurations to create unimodal excitation patterns. The
      stimulation resolution of cochlear implant electrode arrays can potentially be
      improved by increasing the number of electrode contacts in an array.

PMID- 11527038
TI  - Estimating the acoustic reflex threshold from wideband measures of reflectance,
      admittance, and power.
AB  - OBJECTIVE: A method was developed to estimate the contralateral acoustic reflex
      threshold using shifts in wideband energy reflectance, admittance magnitude and
      power. DESIGN: In the first experiment contralateral reflex thresholds for a
      noise activator were estimated on three adult participants using reflectance,
      admittance and power measurements at frequencies from 250 to 8000 Hz. The reflex
      threshold was defined using a magnitude and a correlation technique, both having
      the property of examining the pattern of the reflex-induced shift across a fairly
      broad frequency range (250 to 2000 Hz). In the second experiment, the magnitude
      method was modified to include an F test for the comparison of the magnitude of
      reflex-induced shifts in reflectance, admittance and power relative to response
      differences in a no-activator baseline condition. Data from four additional
      participants then were analyzed across a broader frequency range using a method
      that combined magnitude and correlation methods of estimating reflex thresholds.
      RESULTS: Acoustic reflex thresholds were obtained using reflectance, admittance
      and power-level measures in all subjects in both experiments. Individual reflex
      threshold estimates were as much as 24 dB lower than with the clinical system,
      with an average of approximately 14 dB lower for the three participants in the
      first experiment, and approximately 18 dB lower for the four participants in the
      second experiment. CONCLUSIONS: Wideband measures of reflectance, admittance and
      power were successfully used to estimate acoustic reflex thresholds in seven
      participants. A reflex threshold test was devised based on the magnitude of the
      response shift in the presence of a contralateral activator, and the similarity
      of the response shift spectra across frequency between successive activator
      levels. Across all participants in the study, the new test yielded a more
      sensitive measure of the acoustic reflex threshold than the clinical method. This
      finding has both clinical and theoretical implications for the study of the
      acoustic reflex.

PMID- 11527039
TI  - Effects of amplification and speechreading on consonant recognition by persons
      with impaired hearing.
AB  - OBJECTIVE: This study sought to describe the consonant information provided by
      amplification and by speechreading, and the extent to which such information
      might be complementary when a hearing aid user can see the talker's face. DESIGN:
      Participants were 25 adults with acquired sensorineural hearing losses who wore
      the GN ReSound BT2 Personal Hearing System binaurally. Consonant recognition was
      assessed under four test conditions, each presented at an input level of 50 dB
      SPL: unaided listening without speechreading (baseline), aided listening without
      speechreading, unaided listening with speechreading, and aided listening with
      speechreading. Confusion matrices were generated for each of the four conditions
      to determine overall percent correct for each of 14 consonants, and information
      transmitted for place of articulation, manner of articulation, and voicing
      features. RESULTS: Both amplification and speechreading provided a significant
      improvement in consonant recognition from the baseline condition. Speech-reading
      provided primarily place-of-articulation information, whereas amplification
      provided information about place and manner of articulation, as well as some
      voicing information. CONCLUSIONS: Both amplification and speechreading provided
      place-of-articulation cues. The manner-of-articulation and voicing cues provided
      by amplification, therefore, were generally complementary to speechreading. It
      appears that the synergistic effect of combining the two sources of information
      can be optimized by amplification parameters that provide good audibility in the
      low-to-mid frequencies.

PMID- 11527040
TI  - An investigation of the applicability of the inventory, satisfaction with
      amplification in daily life, at 2 weeks post hearing aid fitting.
AB  - OBJECTIVE: To investigate the applicability of the self-report inventory,
      Satisfaction with Amplification in Daily Life (SADL), at 2 wk postfitting.
      DESIGN: The SADL was completed by two groups of hearing aid users, one fitted 2
      wk before completion, the other at least 1 yr before. All SADLs were completed as
      a paper and pencil exercise, without involvement of an audiologist or other
      clinic staff. All the aid users were Government funded, all were fitted with the
      same model hearing aid, all were over the age of 60 yr, and all were fitted and
      counselled by the same two audiologists. Comparisons were made of the two groups'
      scores on each subscale and Global score, as well as on scores for each
      individual question. RESULTS: All scores for subscales, Global score, and
      individual questions were higher at 2 wk postfitting than at 1 yr. Significant
      differences were found for subscales Positive Effect (p < 0.05), Service and Cost
      (p < 0.025), Negative Features (p < 0.001), as well as for the Global score (p <
      0.001). The only subscale not resulting in a significant difference was Personal
      Image (p > 0.10). It was noted that Negative Features, such as background
      interference, acoustic feedback, and problems with telephone use, apparently take
      longer to be observed than Positive Effects such as improved communication and
      good sound quality. By contrast with some other reported studies, these results
      all display a reduction in self-reported outcome, rather than stability, or even
      improvement, over time. Among other possibilities, this finding may suggest the
      SADL measures something different to that measured by other inventories.
      CONCLUSIONS: The results of this investigation suggest that, if the aim is to
      predict long-term satisfaction with aid fitting, 2 wk postfitting is too early
      for meaningful application of the SADL as an outcome measure. It is possible that
      an earlier stability in SADL scores might be obtained by inclusion of additional
      questions aimed at earlier detection of negative features. Such inclusions may
      detract from one of the SADL's advantages, namely its brevity. It also is
      suggested that the long-term value of self-report methods will depend on
      development of rigorous and scientifically acceptable administration procedures,
      including appropriate times for application.

PMID- 11527041
TI  - Impact of compression and hearing aid style on directional hearing aid benefit
      and performance.
AB  - OBJECTIVE: To evaluate the impact of low-threshold compression and hearing aid
      style (in-the-ear [ITE] versus behind-the-ear [BTE]) on the directional benefit
      and performance of commercially available directional hearing aids. DESIGN: Forty
      seven adult listeners with mild-to-moderate sensorineural hearing loss were fit
      bilaterally with one BTE and four different ITE hearing aids. Speech recognition
      performance was measured through the Connected Speech Test (CST) and Hearing in
      Noise Test (HINT) for a simulated noisy restaurant environment. RESULTS: For both
      the HINT and CST, speech recognition performance was significantly greater for
      subjects fit with directional in comparison with omnidirectional microphone
      hearing aids. Performance was significantly poorer for the BTE instrument in
      comparison with the ITE hearing aids when using omnidirectional microphones. No
      differences were found for directional benefit between compression and linear
      fitting schemes. CONCLUSIONS: No systematic relationship was found between the
      relative directional benefit and hearing aid style; however, the speech
      recognition performance of the subjects was somewhat predictable based on
      Directivity Index measures of the individual hearing aid models. The fact that
      compression did not interact significantly with microphone type agrees well with
      previously reported electroacoustic data.

PMID- 11527042
TI  - Anti-HIV-1 activity in vitro of ceftazidime degradation products.
AB  - Cephalosporins in aqueous solutions generate degradation products that inhibit in
      vitro HIV-1 replication in cell lines, as well as in primary cells (lymphocytes
      and macrophages). This effect is observed at concentrations that do not interfere
      with the normal functions of these cells. Upon chromatographic fractionation of
      an aqueous solution of hydrolysed ceftazidime, a high molecular weight fraction
      (MW 8000) with antiviral activity was isolated. The exact chemical nature of the
      active component responsible for the anti-HIV activity in vitro appears to be
      complex and is currently unknown. Inhibition of HIV-1 reverse transcriptase and
      RNase H activity was observed, however, higher concentrations than those needed
      to inhibit HIV replication were required. The inhibitory action of the hydrolysed
      ceftazidime was manifested during the early phase of the HIV-1 life-cycle.
      Despite a lack of a direct effect of the CD4/gp120 interaction, HIV-1 mediated
      cell fusion was inhibited by the hydrolysed ceftazidime, suggesting that the
      active principle acts in a very early stage of the viral life-cycle.

PMID- 11527043
TI  - 5'-Nor carbocyclic 5'-deoxy-5'-(isobutylthio)adenosine and a 2',3'-dideoxy-2',3'
      didehydro derivative.
AB  - The inhibition of biochemical processes requiring S-adenosylmethionine as a co
      factor have led to many nucleoside-based medicinal agents. Included in this group
      are 5'-deoxy-5'-(isobutylthio)adenosine (SIBA), a nucleoside with antiparasitic,
      antiviral and antiproliferative effects, and 5'-noraristeromycin, a carbocyclic
      derived nucleoside with potent antiviral properties. This report brings together
      the structural components of these two compounds by describing both enantiomers
      of carbocyclic 5-nor SIBA (3 and 4). Owing to the recent interest in 2',3'
      dideoxy-2',3'-didehydro nucleosides as antiviral agents, this derivative of 3 (5)
      is also described. All three compounds were screened against a variety of viruses
      and were found to be inactive at high concentrations or at limiting
      concentrations for the screening methods. The viruses subjected to 3-5 were
      herpes simplex virus types 1 and 2, human cytomegalovirus, vaccinia virus,
      vesicular stomatitis virus, respiratory syncytial virus, varicelIa zoster virus,
      coxsackie virus, parainfluenza-3 virus, sindbis virus, punta toro virus, reovirus
      1, human immunodeficiency virus, influenza virus types A and B, adenovirus type 1
      and measles virus. These results suggest that the C-5' methylene of the C-5' thio
      based carbocyclic nucleosides is important for their antiviral properties.

PMID- 11527044
TI  - Enhancement of anti-herpetic activity of glycyrrhizic acid by physiological
      proteins.
AB  - Some enzymes present in biological fluids, such as lysozyme (LYS) and lactoferrin
      (LAC), are known to possess antibacterial and antiviral activity, against
      herpesviruses in particular. It will be shown in this paper that their
      combination with a natural triterpene, namely glycyrrhizic acid (GLA), gives
      significant results in enhancing the antagonistic activity on HSV1 in in vitro
      assays. Data elaboration was carried out by calculation of the FIC index
      (fractional inhibitory concentration) for each combination of the three compounds
      and by a three-dimensional evaluation of the inhibiting combinatory effects,
      which indicated the percentage of the synergistic action. A FIC index equal to or
      below 0.5 demonstrated a significant synergistic effect between two substances.
      Considering each single compound, the 50% inhibiting doses on viral replication
      (ID50) were 252+/-53 microg/ml for LAC, 497+/-165 microg/ml for LYS and 740+/-125
      microg/ml for GLA. The combination of LAC and GLA showed a clear synergistic
      effect, with a FIC index of 0.08 and a potentiating activity which, for some
      doses, was up to 1.5 log10 of difference (from about 5.5x10(6) to 10(5) pfu/ml).
      The combinations of GLA and LYS, and LYS and LAC showed a less significant
      synergistic activity. These findings led to the conclusion that some
      physiological proteins, even at concentrations usually present in some body
      fluids, may enhance the anti-herpetic activity of a natural compound such as GLA.

PMID- 11527045
TI  - Furano pyrimidines as novel potent and selective anti-VZV agents.
AB  - Bicyclic furano pyrimidine nucleosides have been found to be highly potent and
      selective inhibitors of varicella zoster virus (VZV). They are inactive against
      herpes simplex virus and have been known for several decades as (unwanted)
      synthetic by-products in the Pd-catalysed coupling of acetylenes to 5-iodo
      nucleosides. These fluorescent bicyclic nucleosides are now established as a new
      family of potent antivirals. They are unusual in that they exhibit complete
      specificity for VZV and require an alkyl (or alkylaryl) side-chain for biological
      activity. The latter requirement confers extremely high lipophilicities on these
      compounds, unknown amongst chemotherapeutic nucleosides, which may be of
      considerable importance in formulation, dosing and tissue distribution. The most
      potent compounds reported are p-alkylaryl compounds, with EC50 values below 1 nM
      versus VZV and selectivity index values of around 1,000,000. Here, we review the
      discovery, synthesis, characterization, antiviral profile, SAR, mechanism of
      action and development prospects for this new family of antivirals.

PMID- 11527046
TI  - Differential susceptibility of retroviruses to nucleoside analogues.
AB  - Retroviruses may cause diseases in their vertebrate hosts. They are distinguished
      by their common means of replication involving reverse transcription, a process
      inhibited by nucleoside reverse transcriptase inhibitors (NRTIs) and other
      compounds used in antiretroviral chemotherapy. Previous work on NRTIs has been
      limited to their effect on human immunodeficiency virus (HIV) (for review see Ho
      & Hitchcock, 1989; Weller, 1999) and little information exists regarding the
      efficacy and therapeutic potential of these drugs against other retroviruses. We
      have tested all six NRTIs licensed for HIV treatment [didanosine (ddI),
      zalcitabine (ddC), lamivudine (3TC), stavudine (d4T), zidovudine (AZT) and
      abacavir (ABC)] against seven retroviruses representative of the traditional
      subfamilies: Spumavirinae, Lentivirinae and the Oncovirinae. As expected, each
      drug showed a range of activities against the panel of retroviruses, some drugs
      inhibiting other viruses at concentrations well below those required for HIV.
      Overall, AZT was the most active inhibitor (IC50 range, 0.032-1.0 microM), being
      most active against the Spuma (foamy) viruses. Abacavir was inhibitory for HIV-1,
      MN strain (HIV-1 MN), amphotrophic murine leukemia virus (MLV-A) and simian foamy
      virus type 6 (SFV-6). The least effective inhibitor, 3TC (IC50 range, 0.32->100
      microM), was most potent against simian retrovirus types 1 and 2 (SRV-1, SRV-2)
      and HIV-1, but did not inhibit foamy viruses and MLV-A. Additionally, there were
      differences in the concentration of drug required to inhibit closely related
      viruses. Taken together, these data suggest that NRTIs have a wide spectrum of
      antiretroviral activity and the activity of compounds, even against closely
      related retroviruses, cannot be predicted.

PMID- 11527047
TI  - Antiviral activity and intracellular metabolism of bis(tButylSATE)
      phosphotriester of beta-L-2',3'dideoxyadenosine, a potent inhibitor of HIV and
      HBV replication.
AB  - The beta-L-nucleoside analogue beta-L-2',3'-dideoxy adenosine (beta-L-ddA) has
      been shown to exhibit limited antiviral activities. This was attributed to its
      rapid catabolism through cleavage of the glycosidic bond and poor phosphorylation
      to the nucleotide beta-L-2',3'-dideoxyadenosine-5'-mono phosphate (beta-L-ddAMP)
      (Placidi et al., 2000). However, the nucleotide beta-L-2',3'-dideoxyadenosine-5'
      triphosphate (beta-L-ddATP) inhibited the activity of both HIV-1 reverse
      transcriptase (RT) and viral DNA polymerase isolated from woodchuck hepatitis
      virus-infected serum (a model of hepatitis B) with an inhibitory concentration
      (IC50) of 2.0 microM without inhibiting human DNA polymerases alpha, beta, or
      gamma up to a concentration of 100 microM. These results suggested that prodrugs
      of beta-L-ddAMP may bypass the poor metabolic activation of beta-L-ddA and lead
      to more potent and selective antiviral activity. Therefore, the mononucleoside
      phosphotriester derivative of beta-L-ddAMP incorporating the S-pivaloyl-2
      thioethyl (tButylSATE) groups, beta-L-ddAMP-bis(tButylSATE) was synthesized. Beta
      L-ddAMP-bis(tButylSATE) inhibited HIV replication in human peripheral blood
      mononuclear cells (PBMCs) and HBV replication in 2.2.15 cells with effective
      concentrations (EC50s) of 2 and 80 nM, respectively. Intracellular metabolism of
      beta-L-ddAMP-bis(tButylSATE) demonstrated that beta-L-ddATP was the predominant
      intracellular metabolite in PBMC and liver cells. The intracellular half-life of
      beta-L-ddATP was 5.4 and 9.2 h in HepG2 and PBMCs, respectively. The
      intracellular concentrations of beta-L-ddATP were maintained above the EC50 for
      the inhibition of HIV RT and hepatitis B virus (HBV) for as long as 24 h after
      removal of the drug.

PMID- 11527048
TI  - An assessment tool for predicting fracture risk in postmenopausal women.
AB  - Due to the magnitude of the morbidity and mortality associated with untreated
      osteoporosis, it is essential that high-risk individuals be identified so that
      they can receive appropriate evaluation and treatment. The objective of this
      investigation was to develop a simple clinical assessment tool based on a small
      number of risk factors that could be used by women or their clinicians to assess
      their risk of fractures. Using data from the Study of Osteoporotic Fractures
      (SOF), a total of 7782 women age 65 years and older with bone mineral density
      (BMD) measurements and baseline risk factors were included in the analysis. A
      model with and without BMD T-scores was developed by identifying variables that
      could be easily assessed in either clinical practice or by self-administration.
      The assessment tool, called the FRACTURE Index, is comprised of a set of seven
      variables that include age; BMD T-score, fracture after age 50 years, maternal
      hip fracture after age 50, weight less than or equal to 125 pounds (57 kg),
      smoking status, and use of arms to stand up from a chair. The FRACTURE Index was
      shown to be predictive of hip fracture, as well as vertebral and nonvertebral
      fractures. In addition, this index was validated using the EPIDOS fracture study.
      The FRACTURE Index can be used either with or without BMD testing by older
      postmenopausal women or their clinicians to assess the 5-year risk of hip and
      other osteoporotic fractures, and could be useful in helping to determine the
      need for further evaluation and treatment of these women.

PMID- 11527049
TI  - Bone mineral density of the spine, hip and distal forearm in representative
      samples of the Japanese female population: Japanese Population-Based Osteoporosis
      (JPOS) Study.
AB  - Low bone mineral density (BMD) is one of the most important elements for the
      diagnosis of osteoporosis and screening people with higher risk of fractures. To
      establish the criterion value of BMD for the diagnosis of osteoporosis and to
      estimate the prevalence rate of osteoporosis in Japanese women, we performed a
      Japanese population-based osteoporosis (JPOS) study. The subjects were 4550 women
      aged 15 through 79 years randomly selected from seven municipalities throughout
      Japan. The sample size was determined to ensure that the observed mean BMD would
      remain within 2.5% from the real value with a probability of 0.95 in each of the
      5-year age groups. The study comprised bone mass measurements by dual-energy X
      ray absorptiometry at the spine (L2-4), hip and distal forearm, body size
      measurements and detailed interviews on medical and gynecologic history. After
      excluding those subjects with apparent or suggested abnormalities affecting bone
      mass from 3985 women (87.6%) who completed the study, 3465 women remained and
      served as the subjects. We present 5-year age-specific mean values of BMD and cut
      off values for the diagnosis of osteoporosis according to World Health
      Organization (WHO) and the Japanese Society of Bone and Mineral Research (JSBMR)
      criteria. The cut-off levels at the spine and the distal radius proposed in this
      study were similar to those proposed by the JSBMR but the cut-off level at the
      femoral neck in this study was 4.7% higher than that of the JSBMR. The prevalence
      rates of osteoporosis according to WHO criteria in the present subjects aged 50
      through 79 years were calculated as 38.0% at the spine, 11.6% at the femoral neck
      and 56.8% at the distal one-third site of the radius, and those in the Japanese
      female population of the same age were estimated to be 35.1%, 9.4% and 51.2%,
      respectively. A fivefold difference was observed among the prevalence rates at
      different skeletal sites, which suggests that the different definitions of
      osteoporosis should be established for the different skeletal sites. The
      prevalence rate diagnosed at the femoral neck seemed to be lower in the present
      study than those reported for Caucasians. This might account for a lower
      incidence rate of hip fracture in Japanese women.

PMID- 11527050
TI  - Modeling of cross-sectional bone size, mass and geometry at the proximal radius:
      a study of normal bone development using peripheral quantitative computed
      tomography.
AB  - It is becoming increasingly accepted that bone size is an important determinant
      of bone mass. Studies on the development of bone size may therefore promote a
      better understanding of the basis of diseases which are due to low bone mass.
      Here, we characterize the temporal changes in cross-sectional bone size, geometry
      and mass at the radial diaphysis in healthy subjects from 6 to 40 years of age (n
      = 469; 273 females). Peripheral quantitative computed tomography was used to
      measure total and cortical cross-sectional area, bone mineral content (BMC) and
      volumetric bone mineral density (BMD) at the site of the forearm whose distance
      from the ulnar styloid process corresponded to 65% of forearm length. Over the
      age range of the study, total cross-sectional area increased by 39 mm2 (50%) in
      females and by 85 mm2 (116%) in males. Cortical area increased to a similar
      extent in both sexes. Between 6-7 years and adulthood, BMC increased by 52 mg/mm
      (111%) in females and by 73 mg/mm (140%) in males and was significantly higher in
      males after the age of 15 years. Volumetric BMD increased by 246 mg/cm3 (48%) in
      females but by only 132 mg/cm3 (23%) in males and was significantly higher in
      women than in men. In summary, these data show that BMC in men is higher than in
      women, because periosteal modeling continues longer in boys than in girls.
      Volumetric BMD is higher in women, partly because the size of the marrow cavity
      does not increase in girls as it does in boys.

PMID- 11527051
TI  - Determinants of bone mineral density and spinal fracture risk in postmenopausal
      Japanese women.
AB  - The present study analyzed the factors that determine bone mineral density (BMD)
      and predict spinal fracture risk in postmenopausal Japanese women. Two hundred
      and five postmenopausal Japanese women aged 48-84 years (mean age 64 years) were
      enrolled in the cross-sectional study. BMD of the lumbar spine, femoral neck and
      total body as well as body composition were measured by dual-energy X-ray
      absorptiometry (DXA). Mid-radial BMD was measured by single-photon
      absorptiometry. We also determined serum levels of insulin-like growth factor
      (IGF)-I, IGF binding protein-2, -3 and osteocalcin as well as urinary levels of
      pyridinoline (Pyr), deoxy-Pyr (D-Pyr) and growth hormone. Multiple regression
      analysis revealed that lean body mass (LBM) was positively correlated with BMD at
      all sites. In contrast, femoral neck BMD was highly related to fat mass as well
      as LBM, although fat mass was not an independent correlate of total body and mid
      radial BMD. LBM and urinary D-Pyr were crucial determinants at all sites except
      the mid-radius in stepwise regression analysis. Fat mass and serum IGF-I were
      determinants of femoral neck and mid-radial BMD, respectively. In terms of
      reproductive history, parity affected lumbar BMD. Factors affecting BMD differed
      according to the site. On the other hand, lumbar BMD as well as serum levels of
      IGF-I and albumin were selected as predictors of spinal fracture risk in multiple
      logistic regression analysis. Lumbar BMD, serum IGF-I and LBM were selected in
      women with lumbar BMD above 0.727 g/cm2. In conclusion, the present study
      indicates that LBM is a more important determinant of BMD than fat mass at any
      site except the femoral neck. Age, serum IGF-I and urinary D-Pyr were also
      determinants of BMD, dependent on the regions measured. Lumbar BMD and LBM as
      well as serum levels of IGF-I and albumin were useful markers which predicted the
      risk of osteoporotic spinal fractures in postmenopausal Japanese women.

PMID- 11527052
TI  - Incidence of distal forearm fracture in British men and women.
AB  - Fracture of the distal forearm is one of the most frequent osteoporotic
      fractures. However, there are few data concerning its incidence in Britain. The
      aim of this study was to determine the incidence of distal forearm fracture in
      adult British men and women. Six centers took part in the study: Aberdeen, Hull,
      Nottingham, Portsmouth, Southampton and Truro. At each center, men and women aged
      35 years and over with an incident distal forearm fracture and who resided in the
      catchment area of the main hospital at that center, were identified during a 12
      month period. Incident fractures were identified from all possible point-of
      contact sources in each locality, including accident and emergency records,
      fracture clinics, ward listings and plaster room registers. The population at
      risk was defined geographically according to postcode and the denominator
      obtained from 1991 census data mapped to these postcodes. During the 12 month
      study period, 3161 individuals with distal forearm fracture were identified. The
      age-adjusted incidence, age 35 years and over, was 36.8/10,000 person-years in
      women and 9.0/10,000 person-years in men. In women, the incidence of fracture
      increased progressively with age from the perimenopausal period, while in men the
      incidence remained low until later life. Fractures were more frequently left
      sided (55.6%) and 19.4% of subjects required hospitalization. On the basis of
      these data we estimate that 71,000 adult men and women sustain a distal forearm
      fracture in Britain each year. Compared with previous British surveys the pattern
      of incidence with age appears to have changed in women, the reason for this is
      unclear.

PMID- 11527053
TI  - Awareness of osteoporosis and compliance with management guidelines in patients
      with newly diagnosed low-impact fractures.
AB  - A pre-existing fracture is a strong predictor of additional osteoporotic
      fractures. Consequently, current guidelines emphasize the need for treating
      patients with existing osteoporotic fractures. The present study aimed to assess
      the implementation of osteoporosis guidelines in routine practice. To this end,
      we reviewed the hospital charts of women and men aged 50 years and older with new
      fractures due to low or moderate impact treated in the emergency room, orthopedic
      surgery and rehabilitation departments. Notation of osteoporosis as a
      contributing cause for the fracture, performance of screening laboratory tests
      for possible secondary causes and treatment recommendations were abstracted from
      the record. In addition, we utilized the centralized pharmacy and laboratory
      computerized databases of the largest health maintenance organization in the area
      to follow dispensation of osteoporosis drugs and performance of screening
      laboratory tests in the community following fracture incidents. During the
      corresponding periods of January and February 1998 and 1999, 183 patients aged 50
      years and older with low-impact fractures were treated in the emergency room only
      and 113 were hospitalized. Osteoporosis was rarely mentioned in the medical
      documentation. During the 6 month period after the fracture incident at least 70%
      of the emergency room patients and 62% of the hospitalized patients received no
      osteoporosis drugs. However, an encouraging significant trend toward increasing
      use of osteoporosis drugs, both prior to and after a fracture incident, was noted
      between the two survey periods among the emergency room fracture patients, but
      not among the hospitalized patients. Calcium supplements were the most commonly
      used osteoporosis drug. Bisphosphonates, hormone replacement therapy, raloxifene
      and calcitonin were rarely prescribed. Men were less likely than women to receive
      treatment for osteoporosis. Systematic laboratory evaluations for secondary
      causes of osteoporosis were not performed. We conclude that despite extensive
      attempts at increasing awareness among health professionals and the public at
      large, osteoporosis is still rarely singled out as a problem in patients with
      newly diagnosed low-impact fractures, and the majority of them are not managed
      according to guidelines. Further studies should address specific problems in
      physicians' and patients' attitude that may account for the present situation.

PMID- 11527054
TI  - A comparative study of computed digital absorptiometry and conventional dual
      energy X-ray absorptiometry in postmenopausal women.
AB  - The aim of the study was to evaluate whether computed digital absorptiometry
      (CDA) of the hand might be a useful screening technique for identifying patients
      with postmenopausal osteoporosis and to compare the results of CDA with those of
      dual-energy X-ray absorptiometry (DXA) of the lumbar spine and femoral neck. We
      studied 230 postmenopausal women (mean age 58.4 + 7.9 years). For CDA, bone
      mineral density (BMD) was measured with an AccuDEXA Schick densitometer in the
      third middle phalanx of the nondominant hand. For DXA, BMD of the lumbar spine
      and upper femur was assessed using a DXA Hologic QDR-1000 densitometer. We did a
      comparative analysis (ANOVA) and linear correlation tests. Sensitivity and
      specificity of CDA and receiver operating characteristic (ROC) curves for the
      diagnosis of osteoporosis were calculated. The mean BMD with CDA was 0.445 +/-
      0.084 (T-score: -1.27 +/- 1.29). The mean BMD (g/cm2) with DXA at the lumbar
      spine was 0.877 +/- 0.166 (T-score: -1.52 +/- 1.59) and 0.708 +/- 0.127 at the
      femoral neck (T-score: -1.12 +/- 1.25). BMD at the lumbar spine and femoral neck
      correlated positively with CDA of the hand (r = 0.66 and r = 0.65 respectively,
      p<0.001). When using as cut-off a T-score of -2.5, according to WHO criteria, 76
      women (33%) had osteoporosis of the lumbar spine and/or femoral neck with DXA and
      42 (18%) with CDA (p<0.001). The kappa score for osteoporosis was 0.33 for CDA
      versus spinal DXA and 0.35 for CDA versus femoral DXA. With the cut-off level
      used, sensitivity and specificity of CDA in detecting osteoporosis at the lumbar
      spine were 0.39 and 0.90, respectively; sensitivity and specificity of CDA in
      identifying osteoporosis at the femoral neck were 0.58 and 0.87, respectively.
      The positive predictive value of CDA for osteoporosis was 69% and the negative
      predictive value was 75%. The area under the ROC curve for osteoporosis was 0.822
      +/- 0.028. We conclude that: (a) CDA assessment has a moderate correlation with
      BMD measured by DXA at the lumbar spine and femoral neck; (b) CDA has a low
      sensitivity for the diagnosis of osteoporosis compared with spinal and femoral
      DXA; and (c) predictive values for osteoporosis at both the lumbar spine and
      femoral neck are acceptable.

PMID- 11527055
TI  - Effects of hormonal replacement therapy on bone metabolism in young adults with
      beta-thalassemia major.
AB  - The aim of our cross-sectional study was to evaluate the effects of hormonal
      replacement therapy (HRT) on a population of young thalassemics in order to
      understand better the role of hypogonadism in the balance of bone metabolism.
      Markers of bone turnover and bone mineral density (BMD) were measured in 40 young
      patients (mean age 19.8 +/- 4.5 years) with beta-thalassemia major: 20 subjects
      were biochemically eugonadal. since they were undergoing HRT (group A, treated
      patients), and 20 were hypogonadic, having suspended HRT (group B, untreated
      patients). We also examined 20 healthy control subjects (group C) matched for
      age, anthropometric features and sex to the study groups. Our study shows that
      young thalassemic patients exhibit a significant loss of cortical and trabecular
      bone [aBMD L2-L4: 0.886 +/- 0.052 g/cm2 (group A), 0.726 +/- 0.040 g/cm2 (group
      B), 1.083 +/- 0.090 g/cm (group C); aBMD femoral neck: 0.890 +/- 0.071 g/cm2
      (group A), 0.700 +/- 0.065 g/cm2 (group B), 0.934 +/- 0.076 g/ cm2 (group C)].
      Osteoporosis is only observed at the lumbar level in treated thalassemic
      patients, while in untreated patients it involves the femoral neck also. Bone
      turnover in thalassemic patients is higher in the resorptive phase, than in the
      neoformation phase and this is more marked in hypogonadic untreated patients. In
      conclusion, our data demonstrate the important role played by hypogonadism in the
      development and deterioration of osteopenia/osteoporosis in thalassemia major.
      Consequently, sex hormone replacement therapy represents an appropriate tool in
      the prevention and treatment of osteoporosis in thalassemics, probably together
      with bisphosphonates in cases with severely increased bone resorption.

PMID- 11527056
TI  - Discordant normal ranges for proximal femur bone density in Australia.
AB  - The aim of the study was to investigate the reference ranges currently in use for
      femoral neck bone mineral density (BMD) in Australia. Representative scans were
      obtained of the proximal femur from 78 dual-energy X-ray absorptiometry centers
      across Australia. Femoral neck BMD was standardized using published conversion
      equations and corresponding T-scores calculated using an Australian reference
      range (ARR) and using the NHANES-III reference range (NH3RR). Reported T-scores
      (TR) from the DXA centers were compared with T-scores derived from the NH3RR
      (TNH) and from the ARR (TA). Examination of the regression lines comparing TR
      with TNH, and TR with TA, demonstrated that the reference ranges used by centers
      with Lunar, and some of the Norland and Hologic instruments, differed only
      slightly from both the NH3RR and the ARR. A number of centers, however, with
      Norland or Hologic scanners, were using reference ranges which differed from both
      the NH3RR and ARR. The reference ranges used with these latter Hologic or Norland
      scanners could result in T-score differences of up to I standard deviation in the
      clinically relevant T-score range. The NH3RR was compared with the ARR using a
      set of BMD values covering the clinical range. There was close agreement between
      TNH and corresponding TA, confirming close agreement between the NH3RR and ARR.
      There are thus clinically important differences in the reference ranges currently
      used within Australia for interpretation of femoral neck BMD. For consistency,
      and in view of its validation, the NH3RR is recommended as the most appropriate
      Caucasian normal range in Australia. The ARR for femoral neck BMD does not differ
      significantly from the NH3RR and is also acceptable. Problems relating to the use
      of discordant BMD reference ranges potentially may exist in other countries.

PMID- 11527058
TI  - Weight and body mass index at menarche are associated with premenopausal bone
      mass.
AB  - Adolescence is a critical time for skeletal growth and mineralization. Exposure
      to protective or detrimental factors during this period may influence peak bone
      mass attainment and subsequent development of osteoporosis. In order to evaluate
      the association of body size during adolescence with subsequent adult bone mass,
      we conducted a follow-up study of a community-based cohort of girls who
      participated in a growth and sexual maturation study 30 years ago. Data from the
      original study included age at menarche, height at menarche and weight at
      menarche. Follow-up evaluation of 119 subjects, now premenopausal women ages 40
      45 years, included bone mineral density (BMD) measurements of the total body,
      lumbar spine, femoral neck, total hip, and ultradistal radius by dual-energy X
      ray absorptiometry. After adjustment for current adult weight and other factors
      related to bone mass, weight at menarche was found to be positively associated
      with subsequent adult BMD. Similarly, body mass index (BMI) at menarche was
      positively associated with adult BMD. In contrast, age at menarche was not found
      to predict adult BMD. When the subjects were divided into quartiles based on
      their BMI at menarche, subjects in the lowest quartile of BMI at menarche had
      adult mean BMD that was 8-15% lower at the measured sites compared with subjects
      in the highest quartile of BMI at menarche. In conclusion, low body weight and
      low BMI at menarche appear to be significant predictors of reduced bone mass in
      healthy premenopausal women ages 40-45 years.

PMID- 11527057
TI  - Commencing, continuing and stopping brisk walking: effects on bone mineral
      density, quantitative ultrasound of bone and markers of bone metabolism in
      postmenopausal women.
AB  - Regular walking is associated with reduced risk of fracture and, in our recent
      randomized trial, reduced calcaneal bone loss relative to controls. The present
      follow-up study compared the effects on dual-energy X-ray absorptiometry,
      ultrasound and biochemical indices of bone density and metabolism of (i) taking
      up (ii) continuing with and (iii) ceasing brisk walking for exercise. Subjects
      were 68 postmenopausal women aged 60-70 years. Twenty previously sedentary women
      remained sedentary (Sed/Sed) whilst 17 took up brisk walking (Sed/Walk). Fifteen
      women who had been walking regularly for 1 year returned to their former
      sedentary lifestyle (Walk/Sed), whilst 16 continued brisk walking over a second
      year (Walk/Walk). Bone mineral density (BMD), broadband ultrasonic attenuation
      (BUA), and biochemical markers of bone formation (serum osteocalcin, C-terminal
      propeptide of type I collagen and bone alkaline phosphatase) and resorption
      (urinary deoxypyridinoline) were assessed at baseline and 12 months. Women in the
      Sed/Walk and Walk/Walk groups completed a mean (SEM) of 16.9 (0.7) and 20.8 (1.2)
      min of brisk walking per day, respectively. Changes in BMD did not differ
      significantly between groups. Calcaneal BMD decreased significantly in Walk/Sed
      women [by 2.7 (1.4)%; p = 0.01] whilst changes in other groups were not
      significant. Calcaneal BUA increased significantly (p = 0.02) in Sed/Walk women
      [by 7.4 (3.3)%] relative to other groups. Urinary deoxypyridinoline increased
      over the year in the Sed/Sed group but there were no significant changes in
      biochemical markers in other groups. Women taking up brisk walking for exercise
      showed no change in BMD but a significant increase in calcaneal BUA. There was no
      significant effect on BMD or BUA of continuing brisk walking but calcaneal BMD
      declined on ceasing brisk walking. Bone resorption increased in sedentary women
      but not exercisers, suggesting the effect on exercise on bone in postmenopausal
      women could be through amelioration of this increased turnover.

PMID- 11527059
TI  - Bone density in an immigrant population from Southeast Asia.
AB  - The epidemiology of bone loss in populations of Asian heritage is still poorly
      known. This study compared the skeletal status of a convenience sample of 396
      Southeast Asian immigrants (172 Vietnamese, 171 Cambodians and 53 Laotians)
      residing in Rochester, Minnesota in 1997 with 684 white subjects previously
      recruited from an age-stratified random sample of community residents. Areal bone
      mineral density (BMD, g/cm2) and volumetric bone mineral apparent density (BMAD,
      g/cm3) were determined for lumbar spine and proximal femur using the Hologic QDR
      2000 instrument for the white population and the QDR 4500 for Southeast Asian
      subjects; the machines were cross-calibrated from data on 20 volunteers. Lumbar
      spine BMD was 7% higher in white than Southeast Asian women (p < 0.001), and
      similar results were observed for the femoral neck; lumbar spine BMD was 12%
      higher in white than nonwhite men (p < 0.001). Race-specific discrepancies were
      reduced by calculating BMAD: for premenopausal women, lumbar spine and femoral
      neck differences between whites and Southeast Asians were eliminated; for
      postmenopausal women the lumbar spine differences persisted (p < 0.0001), while
      femoral neck BMAD was actually higher for Southeast Asians. There were no race
      specific differences in femoral neck BMAD among men of any age (p = 0.312), but
      lumbar spine BMAD was less for younger (p = 0.042) but not older (p = 0.693)
      Southeast Asian men. There were differences among the Southeast Asian subgroups,
      but no clear pattern emerged. Predictors of lumbar spine BMAD in Southeast Asian
      women were age (p < 0.001), weight (p = 0.015) and gravidity (p = 0.037). Even
      after adjusting for bone size using BMAD, 32% and 9% of Southeast Asian women and
      men, respectively, would be considered to have osteoporosis at the femoral neck
      and 25% and 4%, respectively, at the lumbar spine. These findings indicate a need
      for culturally sensitive educational interventions for Southeast Asians and for
      physicians to pursue diagnosis and treatment to prevent osteoporosis-related
      disabilities in this population.

PMID- 11527060
TI  - Changes in bone density in patients with ankylosing spondylitis: a two-year
      follow-up study.
AB  - The objectives of the study were to determine the 2 year rate of bone changes in
      patients with ankylosing spondylitis (AS) and, whether bone loss is related to
      physical impairment, systemic inflammation. and therapy. Consecutive outpatients
      fulfilling the modified New York criteria for AS were included. Baseline
      assessment included age, disease duration, treatment, clinical, radiologic and
      laboratory data. Erythrocyte sedimentation rate (ESR) and C-reactive protein
      (CRP) were determined every 6 months. Persistent systemic inflammation was
      defined as mean ESR > or = 28 mm/h or mean CRP > or = 15 mg/l. Bone mineral
      density (BMD) at the lumbar spine and femoral neck was measured by dual-energy X
      ray absorptiometry, at baseline and year 2. Statistical analysis compared the
      baseline and 24 month follow-up BMD data, and determined whether baseline data,
      and persistent systemic inflammation during the 2 years, were related to the 24
      month percentage changes in BMD. Fifty-four patients (35 men, 19 women; mean age
      37.3 +/- 11.3 years, mean disease duration 12.4 +/- 8.6 years) were included.
      After 2 years, BMD did not change at the lumbar spine (+0.75% +/- 3.5, p = 0.23),
      and decreased at the femoral neck (-1.6% +/- 4, p = 0.006). The 24 month
      percentage change in femoral neck BMD was related to persistent systemic
      inflammation, defined using ESR (mean percentage change -4.1% +/- 5.7 and -1.2%
      +/- 3.9 in patients with and without persistent inflammation; respectively; p =
      0.007). These results suggest that persistent inflammation might be an etiologic
      factor of bone loss in AS.

PMID- 11527061
TI  - Bone loss from the hand in women following distal forearm fracture.
AB  - Bone loss occurs after distal forearm fracture, but it is unclear if this bone
      loss is fully recovered. We designed a cross-sectional study to evaluate the time
      course of the bone loss from the hand after distal forearm fracture. We
      identified 40 women who had a fracture of the distal forearm within the previous
      4.5 years. Their ages ranged from 42 to 81 (mean 64 years) and time since
      fracture 6 to 54 (mean 28 months). These were compared with 95 women (mean age
      67, range 57 to 80 years) from a population-based cohort. Lumbar spine (LS) and
      hand bone mineral density (BMD) were measured in all subjects using a Hologic QDR
      1000/W densitometer. Ultrasound of the fingers of both hands was measured in the
      forearm fracture group using a DBM Sonic 1200 R model. Compared to controls, LS
      BMD was decreased by 6.4% (p<0.001), non-fractured hand by 3.2% (p<0.001) and the
      fractured hand by 6.1% (p<0.001) in the forearm fracture group. The mean
      difference in bone density between the fractured and non-fractured hand was
      0.0207 g/cm2, the average value for the non-fractured hand being 0.304 g/cm2. The
      decement in hand BMD was equivalent to 6.2% (p<0.0001). The difference in hand
      BMD between the fractured and non-fractured side was greatest when the time since
      fracture was short; there was no further difference in hand BMD after 2 years.
      Ultrasound showed a mean difference of 18.7 m/s in amplitude-dependent speed of
      sound (AD-SoS) with the average value being 1893 m/s. A 1.0% decrease was
      observed in the fractured hand AD-SoS (p<0.05). A strong relationship was
      observed between AD-SoS and BMD in both hands (r = 0.70, p<0.001). We conclude
      that distal forearm fracture results in a significant decrease in hand BMD that
      is partially reversible. The decrease in hand BMD is reflected in the ultrasound
      properties of the finger phalanx.

PMID- 11527062
TI  - The analgesic efficacy of bee venom acupuncture for knee osteoarthritis: a
      comparative study with needle acupuncture.
AB  - The aim of this investigation was to determine whether bee venom (BV)
      administered directly into an acupoint was a clinically effective and safe method
      for relieving the pain of patients with knee osteoarthritis (OA) as compared to
      traditional needle acupuncture. We evaluated the efficacy of BV acupuncture using
      both pain relief scores and computerized infrared thermography (IRT) following 4
      weeks of BV acupuncture treatment. We observed that a significantly higher
      proportion of subjects receiving BV acupuncture reported substantial pain relief
      as compared with those receiving traditional needle acupuncture therapy.
      Furthermore, the IRT score was significantly improved and paralleled the level of
      pain relief.

PMID- 11527063
TI  - Objective assessment of the sympatholytic action of the Nei-Kuan acupoint.
AB  - From animal experiments and clinical trials, we can think that acupuncture of Nei
      Kuan (EH-6) is effective in the control of some vegetative functions. We have
      tried to determine the real reach of these assumptions by means of simple
      quantitative measurement methods, such as detection of cardiac frequency and
      systolic and diastolic blood pressure, and the sympathetic electrical response.
      The experiments were performed on 29 healthy volunteers. Basal values of these
      parameters were recorded, and also after orthodox Nei-Kuan acupuncture, non
      acupunctural point puncture, supine lying by 15 min, Chu-Tze (EH-3) acupuncture
      and bipolar electrical stimulus of the median nerve at the Nei-Kuan level in the
      wrist. Such conditions were designed to evaluate non-specific puncture, repose
      and direct median nerve stimulation influences in the effects of Nei-Kuan
      acupuncture. We conclude that Nei-Kuan acupuncture strongly inhibits sympathetic
      tone, with reduction of cardiac frequency, systolic blood pressure and an
      important reduction of the amplitude of the sympathetic electrical response; the
      latency of the electrical response was also prolonged. Some weak effects on blood
      pressure and cardiac frequency were observed also, as non-specific effects of
      puncture and median nerve stimulation. From previous anatomical data, we
      hypothesize that the level of such actions is suprametameric, with strong
      implication of the diencephalon and cerebral cortex.

PMID- 11527064
TI  - Studies of the central neural pathways to the stomach and Zusanli (ST36).
AB  - The purpose of this morphological study was to investigate the relation between
      the meridian, meridian points and viscera using neuroanatomical tracers. The
      common locations of the spinal cord and brain projecting to the stomach and
      Zusanli were observed following injection of CTB (cholera toxin B subunit) and
      pseudorabies viruses (PRV-Ba, Bartha strain and PRV-Ba-Gal, galactosidase
      insertion) into the stomach and Zusanli (ST36). After 4-5 days of survival
      following injection into twelve rats, they were perfused, and their spinal cords
      and brains were frozen sectioned (30 microm). These sections were stained by X
      gal histochemical, CTB and PRV-Ba immunohistochemical staining methods, and
      examined with the light microscope. The results were as follows: Commonly labeled
      medulla oblongata regions were dorsal motor nucleus of vagus nerve (DMV), nucleus
      tractus solitarius (NTS) and area postrema (AP) following injection of CTB and
      PRV-Ba-Gal into stomach and Zusanli, respectively. In the spinal cord, commonly
      labeled neurons were found in thoracic, lumbar and sacral spinal segments.
      Densely labeled areas were found in lamina IV, V, VII (intermediolateral nucleus)
      and X of the spinal cord. In the brain, commonly labeled neurons were found in
      the Al noradrenalin cells/Cl adrenalin cells/caudoventrolateral reticular
      nucleus, dorsal motor nucleus of vagus nerve, nucleus tractus solitarius, area
      postrema, raphe obscurus nucleus, raphe pallidus nucleus, raphe magnus nucleus,
      gigantocellular nucleus, locus coeruleus, parabrachial nucleus, Kolliker-Fuse
      nucleus, A5 cell group, central gray matter, paraventricular hypothalamic
      nucleus, lateral hypothalamic nucleus, retrochiasmatic hypothalamic nucleus, bed
      nucleus of stria terminalis and amygdaloid nucleus. Thus central autonomic center
      project both to the stomach and Zusanli. These morphological results suggest that
      there is a commonality of CNS cell groups in brain controlling stomach (viscera)
      and Zusanli (limb).

PMID- 11527065
TI  - The effectiveness of Tsu-San-Li (St-36) and Tai-Chung (Li-3) acupoints for
      treatment of acute liver damage in rats.
AB  - This study investigated the effects of acupuncture on carbon tetrachloride (CCl4)
      induced acute liver injury in male rats (n=36). The experimental groups were
      injected with CCl4 before, during, or after acupuncture therapy. Acupoints
      similar to the human Tsu-San-Li (St-36) and Tai-Chung (Li-3) were needled
      bilaterally. Rats treated with CCl4 had higher levels of serum glutamate-oxalate
      transaminase (sGOT) and serum glutamate-pyruvate-transaminase (sGPT). Comparing
      the experimental groups, biochemical and pathological parameters of liver injury
      were significantly reduced when rats were acupunctured after, not before, CCl4
      induced hepatotoxicity. Acupuncture at the Tsu-San-Li and Tai-Chung acupoints
      cannot prevent acute liver injury but may be effective in treating liver injury
      induced by carbon tetrachloride in rats.

PMID- 11527066
TI  - Changes in peripheral lymphocyte subpopulations after direct moxibustion.
AB  - We measured peripheral lymphocyte subpopulations after direct moxibustion using
      moxa cones the size of a half-rice grain. In humans at 2 hrs after the direct
      moxibustion, NK cell percentage decreased and CD4/CD8 ratio increased
      significantly. Although the same trends were observed in the control session,
      those changes were not statistically significant. In rabbits at 3 and 12 hrs
      after direct moxibustion, CD4/CD8 ratio significantly increased, and recovered at
      between 24 and 72 hrs after treatment. Similarly, the CD4/CD8 ratio significantly
      increased in the control session, but they seemed to have a shorter duration.
      Although it is not yet clear whether the effects are beneficial, we found that
      direct moxibustion influences the immune system at least transiently.

PMID- 11527067
TI  - Qi therapy as an intervention to reduce chronic pain and to enhance mood in
      elderly subjects: a pilot study.
AB  - Qi therapy (or external Qi) is an oriental complementary therapy preventing,
      curing disease and strengthens health and improving the human potentiality
      through regulation of body. It is increasingly being used to improve the quality
      of life, but there is little direct evidence of its efficacy. This study assessed
      the effects of Qi therapy (QT) on reducing pain and enhancing mood states in
      elderly subjects with chronic pain. We studied 40 elderly participants with
      chronic pain, who were randomly allocated to receive QT (n=20) or standard care
      (n=20). The experimental group receives Qi therapy twice a week for 2 weeks
      (total 4 times), and control group received general care at the same time and the
      same amount of duration. We measured pain level and Profile of Mood State (POMS)
      to explore participants' response to Qi therapy. There was a significant
      reduction in pain (p<0.0001) after QT and an improved positive mood state
      (p<0.0001). These findings suggest that Qi therapy may have a role in helping the
      elderly to cope with their pain and mood disturbances.

PMID- 11527068
TI  - Studies on the psychosomatic functioning of ill-health according to Eastern and
      Western medicine 6. Psychosomatic characteristics of anxiety and depression.
AB  - In the accompanying paper "Psychosomatic Characteristics of Anxiety and the
      Anxiety-Affinitive Constitution (Provisional Term) in Medical Students," we
      suggest that an assessment of the relationship between anxiety and the state of
      thoracic-abdominal balance of breathing, and the creation of an anxiety
      affinitive constitution index (AACI) derived from that assessment, will be
      indispensable for furthering research in the future. Using the tenets of Oriental
      psychosomatic medicine, we examined in this research medical students (N=104)
      from whom we had received fully-informed consent for the research in writing, and
      patients who met the DSM-IV diagnostic criteria for anxiety disorders (N=18) and
      major depressive episodes (N=20). We then identified their anxiety and depressive
      psychosomatic traits in accordance with an assessment of the relationship between
      anxiety and the state of their thoracic-abdominal balance of breathing, and the
      AACI derived from that assessment. We performed a multiple regression analysis
      with the STAI trait anxiety as the dependent variable, and the parameters of the
      somatic tests as the independent variables. We obtained the formula that AACI=
      62.9 + 72.9 x the thoracic/abdominal respiratory movement ratio (the fractal
      dimension value for the thoracic respiratory curve/the fractal dimension value
      for the abdominal respiratory curve) + 22.5 x the horizontal eye movement (the
      fractal dimension value) + 2.4 x the dental indentation of the tongue (existence,
      1; none 0). We then obtained data regarding a symptomatological, constitutional,
      and nosological, diagnosis of anxiety and depression based on the AACI values of
      the Student's t test calculated for the medical students and the anxiety disorder
      patients and patients with major depressive episodes, and a statistical analysis
      using ANOVA. We believe the AACI we created in this research will be very
      important and significant for the preventive treatment of lifestyle illnesses and
      stress-related diseases.

PMID- 11527069
TI  - Modulation of Chelidonii herba on GABA activated chloride current in rat PAG
      neurons.
AB  - Modulation of Chelidonii herba on gamma-aminobutyric acid (GABA) activated
      chloride current in the acutely dissociated periaqueductal gray (PAG) neuron was
      studied by nystatin-perforated patch-clamp technique. High concentrations of
      Chelidonii herba elicited ion current, that was blocked by bicuculline. Low
      concentrations reduced the GABA activated current in PAG. Two types of inhibitory
      action of Chelidonii herba on GABA activated current have been implicated in PAG.
      One is the inhibitory action of Chelidonii herba on GABA was abolished by
      naltrexone and the other is that of Chelidonii herba was potentiated by
      naltrexone. In addition, all of two types of action of Chelidonii herba are
      linked to pertussis toxin-sensitive GTP-binding proteins. These results suggest
      that the inhibitory modulation of Chelidonii herba on GABA activated current via
      G-proteins in PAG neuron is an important analgesic mechanism.

PMID- 11527070
TI  - Administration of chinese herbal medicines facilitates the locomotor activity in
      dystrophin-deficient mice.
AB  - The purpose of this study was to access the effects of chinese herbal medicines
      on Duchenne muscular dystrophy (DMD). We use dystrophin-deficient mice (mdx), an
      animal model of DMD, to evaluate the effect of chinese herbal medicines on
      locomotor activity. The consumption of water for each mouse was controlled during
      the three-month experimental session. Each mouse was allowed to drink 3 ml water
      with or without herbal medicines daily for three months. The estimated intake of
      chinese herbal medicine in adult mdx mouse with 30 g weight is 100 mg/kg per day,
      close to a dose used in human. The locomotor activity of the mdx mice was
      measured every month. Monitoring the locomotor activity of mdx mice after three
      month administration of chinese herbal medicines, the results showed that liu-wei
      di-huang-wan (LDW) and san-lin-pai-tsu-san (SPS) can facilitate locomotor
      activity with the parameters of horizontal activity, total distance, number of
      movements, movement time, vertical activity, number of vertical movements,
      vertical movement time, stereotypy, number of stereotyped movements, and
      stereotyped movement time. These results suggest that either LDW or SPS can act
      as a potent herbal medicine for the pharmacological treatment of DMD patients.

PMID- 11527071
TI  - Effect of Alpinia oxyphylla fruit extract on compound 48/80-induced anaphylactic
      reactions.
AB  - The effect of the aqueous extract of Alpinia oxyphylla Miq. (Zingiberaceae)
      fruits (AOFE) on anaphylactic reaction was investigated. AOFE completely
      inhibited compound 48/80-induced systemic anaphylactic shock at dose of 1.0 g/kg.
      When AOFE was pretreated at concentrations ranging from 0.01 to 1.0 g/kg, the
      plasma histamine levels induced by compound 48/80 were reduced in a dose
      dependent manner. AOFE also inhibited the histamine release from rat peritoneal
      mast cells (RPMC) by compound 48/80. The level of cAMP in RPMC, when AOFE was
      added, transiently and significantly increased about 4-fold compared with that of
      basal cells. These results indicate that AOFE may be beneficial in the treatment
      of non-specific anaphylactic reactions.

PMID- 11527072
TI  - Antileukemic activity of Bidens pilosa L. var. minor (Blume) Sherff and
      Houttuynia cordata Thunb.
AB  - To evaluate the anti-leukemic activity of Bidens pilosa L. var. minor (Blume)
      Sherff and Houttuynia cordata Thunb., cytotoxicity tests with an XTT-based
      colorimetric assay were used. Five leukemic cell lines, namely L1210, U937, K562,
      Raji and P3HR1, were cultured with hot water extracts of B. pilosa var. minor or
      H. cordata. Hot water extracts of B. pilosa var. minor inhibited these five
      leukemic cells with IC50s between 145 microg/ml and 586 microg/ml. The effect was
      greatest on four cell lines, namely L1210, P3MR1, Raji and K562, with IC50s below
      200 microg/ml and a selective index of more than 5. Hot water extract of H.
      cordata inhibited these five leukemic cells with IC50s between 478 microg/ml and
      662 microg/ml. The selective index was between 1.5 and 2.1. B. pilosa var. minor
      was more effective than H. cordata in inhibiting most of the leukemic cells in
      our study. We suggest that B. pilosa L. var. minor (Blume) Sherff may prove to be
      a useful medicinal plant for treating leukemia.

PMID- 11527073
TI  - Ethyl acetate extract of the stem bark of Cudrania tricuspidata induces apoptosis
      in human leukemia HL-60 cells.
AB  - Apoptosis is now widely accepted as playing a role in tumorigenesis. An effective
      compound which can kill tumors via apoptotic pathway appears to be a relevant
      strategy to suppress various human tumors. The ethyl acetate extract from the
      stem bark of Cudrania tricuspidata (EACT) showed dose- and time-dependent
      cytotoxic effects on human leukemia HL-60 cells. DNA fragmentation and
      morphological changes, accompanied by condensed and fragmented nuclei, were
      observed in the cells cultured for 6 hr with EACT. These results suggest that the
      cytotoxicity of the crude extract from Cudrania tricuspidata against HL-60 cells
      is due to apoptosis.

PMID- 11527074
TI  - Effects of (-)-menthol on arylamine N-acetyltransferase activity in human liver
      tumor cells.
AB  - To evaluate whether or not (-)-menthol affects arylamine N-acetyltransferase
      (NAT) activity, we selected human liver tumor cell line (J 5) for examination. By
      using high performance liquid chromatography, NAT activity for acetylation of 2
      aminofluorene (AF) was determined. (-)-Menthol displayed a dose-dependent
      inhibition to cytosolic NAT activity. Time-course experiments showed that NAT
      activity measured from intact human liver tumor cells was inhibited by (-)
      menthol for up to 24 hrs. But in human liver tumor intact cells, the low doses
      (0.0032 and 0.032 mM) of (-)-menthol promoted the NAT activity and the high doses
      (3.2 and 32 mM) of (-)-menthol inhibited NAT activity and the 0.32 mM (-)-menthol
      did not show any significant differences between control and (-)-menthol treated
      groups. Using standard steady-state kinetic analysis, it was demonstrated that (
      )-menthol was a possible uncompetitive inhibitor (decrease Km and Vmax) to NAT
      activity in cytosols. This report is the first demonstration which showed (-)
      menthol affect on human liver tumor cells NAT activity.

PMID- 11527075
TI  - Anticonvulsive and free radical scavenging activities of Gastrodia elata Bl. in
      kainic acid-treated rats.
AB  - Gastrodia elata Bl. (GE) is a traditional Chinese herb that is commonly used in
      Chinese communities to treat convulsive disorders such as epilepsy. The purpose
      of the present study was to determine the anticonvulsive and free radical
      activities of GE in rats. In vitro studies were conducted by using brain tissue
      from 6 male Sprague-Dawley (SD) rats treated with 120 microg/ml of kainic acid
      (KA), with or without the addition of various concentrations of GE. In vivo
      studies were conducted in a total of 30 male SD rats divided into 5 groups of 6
      rats which were treated as follows: 1) the normal group received an
      intraperitoneal injection (i.p.) of PBS (Phosphate buffer saline, 1 ml/kg); 2)
      the control group received KA (12 mg/kg) i.p.; 3) the GE 1.0 group received oral
      administration of GE 1.0 g/kg 30 min prior to KA administration; 4) the GE 0.5
      group received oral administration of GE 0.5 g/kg 30 min prior to KA
      administration; 5) the PH group received oral administration of phenytoin 20
      mg/kg 30 min prior to KA administration. Seizures were verified by behavioral
      observations, electroencephalograph (EEG) and electromyography (EMG). Lipid
      peroxide levels in the rat brain, luminol chemiluminescence (CL) and lucigenin-CL
      in the peripheral blood were measured simultaneously after behavioral
      observations. The results indicate that GE administration significantly reduced
      KA-induced lipid peroxide levels in vitro. Oral administration of GE 1.0 g/kg and
      phenytoin 20 mg/kg significantly reduced counts of wet dog shakes (WDS), paw
      tremor (PT) and facial myoclonia (FM) in KA-treated rats. In addition, oral
      administration of GE 1.0 g/kg significantly delayed the onset of WDS, from 30 min
      in the control group to 46 min in the 0.5 g/kg group, and 63 min in the GE 1.0
      g/kg group. A significantly reduced level of lipid peroxides in the rat brain was
      found in the GE 1.0 g/kg, 0.5 g/kg, and phenytoin 20 mg/kg groups. The GE 1.0
      g/kg group showed significant reduction of luminol-CL and lucigenin-CL counts in
      the peripheral blood compared to the control group. The results of the present
      study demonstrate that GE has anticonvulsive and free radical scavenging
      activities. Further studies are needed to determine the clinical effectiveness of
      GE as an anticonvulsant in humans.

PMID- 11527077
TI  - Suppression of collagen-induced arthritis in rats by continuous administration of
      dae-bang-poong-tang (da-fang-feng-tang).
AB  - Although dae-bang-poong-tang (an herbal formula of 15 herbs)-treated rats
      exhibited a mild inflammation, the significant histological changes including a
      marked infiltration of inflammatory cells in the synovium and damaged articular
      cartilages were not observed. The staining abilities of the cartilage such as
      periodic acid Schiff s reaction in the interterritorial matrix of hyaline
      cartilage, alcian blue and aldehyde fuchsin staining in the capsule of
      chondrocytes and in the interterritorial matrix of articular cartilage and Con A,
      sWGA and BSL-1 affinities of chondrocytes tended to decrease in the rats with
      collagen-induced arthritis compared with normal rats. Decreased stainabilities
      and affinities were almost recovered in the dae-bang-poong-tang-treated rats. In
      the collagen-induced rats, iNOS expression in the synovial lining cells and
      subsynovial tissue were significantly increased and numerous strong
      immunoreactive cells were demonstrated in the subsynovial tissue. Somewhat
      decreased immunoreaction of iNOS was shown in the synovial lining cells and
      subsynovial tissue of dae-bang-poong-tang-treated rats. It was concluded that dae
      bang-poong-tang showed a notable protection against histological changes and
      histochemical staining, and it acted as an inhibitor of iNOS expression. Dae-bang
      poong-tang may be used as a complementary therapeutic agent to alleviate the
      rheumatoid arthritis.

PMID- 11527076
TI  - Effects of Puerariae Flos and Puerariae Radix extracts on antioxidant enzymes in
      ethanol-treated rats.
AB  - This study was performed to investigate the effect of Puerariae Flos (PF) and
      Puerariae Radix (PR) water extracts on the activities and mRNA expression of
      three hepatic antioxidant enzymes in ethanol-treated rats. Male Sprague-Dawley
      rats were divided into four groups, a control, ethanol-treated, ethanol plus PF
      treated, and ethanol plus PR-treated group with seven rats per group. Ethanol (25
      % v/v, 5 g/kg body weight) was orally administered once a day for 5 weeks. The PF
      and PR water extracts were supplemented in a diet based on 1.2 g of raw PF or
      PR/kg body weight/day. Ethanol administration without the PF or PR supplement
      significantly lowered the activities of hepatic Cu/Zn SOD and catalase (CAT),
      whereas it increased the hepatic GSH-Px activity. However, the PF and PR
      supplementation resulted in a significant increase in the Cu/Zn SOD and/or CAT
      activities and a significant decrease in the GSH-Px activity in the ethanol
      treated rats. The mRNA levels of these antioxidant enzymes in the ethanol-treated
      rats were normalized to the control level by the PF or PR supplement. The hepatic
      glutathione content, which was significantly lower in the ethanol-treated group
      than in the control group, was also normalized to the control level by
      supplementing with either PF or PR. The PF or PR supplement resulted in lowering
      the hepatic malondialdehyde to the control level in the ethanol-treated rats.

PMID- 11527078
TI  - Treatment with sheng-mai-san reduces myocardial infarct size through activation
      of protein kinase C and opening of mitochondrial KATP channel.
AB  - Sheng-mei-san (SMS), a traditional Chinese formulation comprising Radix Ginseng,
      Radix Ophiopogonis and Fructus Schisandrae, has long been used for more than 700
      years for patients with coronary heart disease. We attempted to clarify 1)
      whether SMS reduces myocardial infarct size, and 2) whether the infarct size
      reducing effect of SMS is related to activation of protein kinase C and the
      opening of the mitochondrial KATP channels in Japanese white rabbits without
      collateral circulation. The results indicate that three days treatment but not
      acute treatment with SMS reduces myocardial infarct size through activation of
      protein kinase C and opening of the mitochondrial KATP channels.

PMID- 11527079
TI  - Clinical implications of pulsatile hormone signals.
AB  - In all biological systems, the information content of hormonal signals is
      conveyed by the modalities of pulsatile hormone secretion. New mathematical tools
      for the analysis of pulsatile behaviour and increasing knowledge of the sources
      of signal variability have enabled us to recognize altered hormonal pulsatility
      associated with human disease. Its consequences for our understanding of disease
      mechanisms, for diagnostic procedures and for therapeutic decisions are discussed
      at the level of single hormones. Increased disorderliness of hormone secretion is
      a hallmark of pituitary adenomas, indicating functional subsystem autonomy. The
      effects on target tissues of changing growth hormone therapy from low-frequency
      administration to long-acting preparations are still incompletely understood. In
      contrast, the gonadotropic axis is a paradigm for the successful therapeutic use
      of induced pulsatility changes, where therapy with long-acting gonadotropin
      releasing hormone (GnRH) agonists suppresses endogenous gonadotropin pulses and
      gonadal function, and pulsatile GnRH administration is used to restore normal
      gonadal function. Future development of endocrine therapies will depend on our
      knowledge of hormonal pulsatility.

PMID- 11527080
TI  - Growth hormone receptor antagonists: discovery and potential uses.
AB  - Serum levels of growth hormone (GH) in the human body vary and can influence the
      levels of insulin-like growth factor I (IGF-1). Low levels of GH can result in a
      dwarf phenotype and have been positively correlated with an increased life
      expectancy. High levels of GH can lead to gigantism or a clinical syndrome termed
      acromegaly, and also have been implicated in diabetic eye and kidney damage.
      Additionally, it has been postulated that the GH-IGF-I system can be involved in
      several types of cancers. Overall, both elevated and suppressed circulating
      levels of GH can have pronounced physiological effects. More than a decade ago a
      new class of drug, a GH antagonist, was discovered. It is now being tested for
      its ability to combat the effects of high circulating levels of GH. In this
      review, we will discuss some of the detrimental actions of GH and how a GH
      antagonist may be used to combat these effects.

PMID- 11527081
TI  - Experience with pegvisomant in the treatment of acromegaly.
AB  - Established modalities of therapy for acromegaly (surgical adenomectomy, external
      beam pituitary irradiation, oral dopamine agonists, and injectable somatostatin
      analogues) have as their common goal the lowering of circulating growth hormone
      (GH) levels, with a consequent reduction in serum insulin-like growth factor I
      (IGF-I). Pegvisomant is a GH receptor antagonist that inhibits GH receptor
      dimerization and has a powerful ability to lower serum IGF-I levels in patients
      with active acromegaly. Currently available data suggest that pegvisomant is an
      effective treatment for acromegaly that is safe, well tolerated, and not
      associated with expansion of residual pituitary tumour over the time period
      studied.

PMID- 11527082
TI  - Potential use of growth hormone receptor antagonist in the treatment of diabetic
      kidney disease.
AB  - Various growth factors have been proposed to be players in the development of
      diabetic microvascular complications. In particular, growth hormone (GH) and
      insulin-like growth factors (IGFs) have a long history in diabetes, with
      measurable effects on the development of diabetic kidney disease in experimental
      animal models through changes in a complex intrarenal system. Furthermore, new
      data obtained in knock-out (KO) mice with GH receptor (GHR)/GH-binding protein
      (GHBP) gene disruption have shown that these animals are protected against
      diabetes-induced renal changes. The recent development of specific inhibitors of
      GH action, i.e. specific GHR antagonists (GHRAs), has opened the possibility that
      this group of inhibitors may be used as therapeutic agents in conditions where GH
      and IGFs have been suggested to play a pathophysiological role, such as late
      complications of diabetes. Accordingly, new data from studies in diabetic mice
      treated with a GHRA (G120K-PEG) from the onset of diabetes, showed normalization
      of the diabetes-associated renal hypertrophy and glomerular enlargement and, most
      importantly, a lowering effect on the diabetes-induced rise in urinary albumin
      excretion (UAE), a marker of renal damage. In addition, late intervention with
      GHRAs alone or in combination with angiotensin-converting enzyme inhibitors in
      non-obese diabetic mice with manifest renal changes, showed regression in some of
      the diabetes-associated renal changes (e.g. UAE and renal hypertrophy). These
      experimental data strongly suggest that GHR blockade may present a new concept in
      the treatment of diabetic renal complications. Future studies are warranted to
      characterize fully the clinical potential of GHRAs as drugs for treatment of
      diabetic complications in general.

PMID- 11527083
TI  - Cancer and the potential place for growth hormone receptor antagonist therapy.
AB  - Pegvisomant is a recombinant protein, structurally similar to natural human
      growth hormone (GH), which is capable of binding to the GH receptor as a
      competitive antagonist. As well as being evaluated for the treatment of
      acromegaly, pegvisomant is being investigated as a possible antineoplastic agent,
      initially in mice. So far, in vitro efficacy against meningioma and in vivo
      efficacy against colon and breast cancer cell lines have been examined.

PMID- 11527084
TI  - Insulin signalling through ultradian oscillations.
AB  - Periodic oscillations appear to be a characteristic of insulin secretion at
      various different levels. Very rapid pulsations are seen in the isolated beta
      cell and islet, while rapid (10- to 15-min) pulsations are seen both in the
      intact organism and in the isolated pancreas. Ultradian oscillations,
      particularly evident in situations of sustained exogenous glucose loading, appear
      to be a characteristic of intact organisms and have been hypothesized to be
      intrinsic to the normal glucose-insulin feedback system. Many of the features
      seen in experimental situations and in abnormalities of the system can be
      predicted by computer modelling of this system, supporting this hypothesis. A
      further theoretical feature of this hypothesis, borne out by experiment, is the
      ability to entrain insulin pulsatility by oscillations in an exogenous glucose
      infusion. Identification of defective ultradian oscillations and entrainment can
      identify subtle abnormalities of insulin sensitivity and pancreatic function, and
      restoration of normal function can be demonstrated after pharmaceutical
      intervention.

PMID- 11527085
TI  - Neurophysiological regulation and target-tissue impact of the pulsatile mode of
      growth hormone secretion in the human.
AB  - Neuroendocrine axes function as an ensemble of regulatory loci which communicate
      and maintain homeostasis via time-delayed blood-borne signals. The growth hormone
      (GH)-insulin-like growth factor I (IGF-I) feedback axis sustains a vividly
      pulsatile mode of interglandular signalling. Pulsatility is driven jointly by
      hypothalamic GH-releasing hormone (GHRH) and GH-releasing peptide (GHRP), and
      modulated by somatostatinergic restraint. Paradoxically, intermittent
      somatostatin inputs also facilitate somatotrope-cell responses to recurrent
      secretagogue stimuli, thereby amplifying pulsatile GH secretion. A concurrent low
      basal (8-12% of normal total) rate of GH release is controlled positively by GHRH
      and GHRP and negatively by somatostatin. Sex-steroid hormones (such as oestradiol
      and aromatizable androgen) and normal female and male puberty augment GH
      secretory-burst mass 1.8- to 3.5-fold, whereas ageing, relative obesity, physical
      inactivity, hypogonadism, and hypopituitarism mute the amplitude/mass of
      pulsatile GH output. An abrupt rise in circulating GH concentration stimulates
      rapid internalization of the GH receptor in peripheral target tissues, and evokes
      second-messenger nuclear signalling via the STAT 5b pathway. Discrete GH peaks
      stimulate linear (skeletal) growth and drive muscle IGF-I gene expression more
      effectually than basal (time-invariant) GH exposure. A brief pulse of GH can
      saturate the plasma GH-binding protein system and achieve prolonged plasma GH
      concentrations by convolution with peripheral distribution and clearance
      mechanisms. A single burst of GH secretion also feeds back after a short latency
      on central nervous system (CNS) regulatory centres via specific brain GH
      receptors to activate somatostatinergic and reciprocally subdue GHRH outflow.
      This autoregulatory loop probably contributes to the time-dependent
      physiologically pulsatile dynamics of the GH axis. More slowly varying systemic
      IGF-I concentrations may also damp GH secretory pulse amplitude by delayed
      negative-feedback actions. According to this simplified construct, GH pulsatility
      emerges due to time-ordered multivalent interfaces among GHRH/GHRP feedforward
      and somatostatin, GH and IGF-I feedback signals. Resultant GH pulses trigger
      tissue-specific gene expression, thereby promoting skeletal and muscular growth,
      metabolic and body compositional adaptations, and CNS reactions that jointly
      maintain health and homeostasis.

PMID- 11527086
TI  - Overview of pulse actions in the human.
AB  - Many hormones are secreted in a pulsatile fashion. The knowledge of this
      pulsatility has brought about detailed descriptions of hormone fluctuations
      employing sophisticated methods, but only a few advantages in patient care. Two
      areas of research comprise the analysis of the effects of single pulses on target
      cells and the development of circadian rhythms in newborn humans. This article
      gives an overview of these aspects of hormone physiology.

PMID- 11527087
TI  - Growth hormone treatment in adults: is there a true gender difference?
AB  - The importance of growth hormone (GH) deficiency in adults became evident at the
      end of the 1980s, when the first clinical studies on GH replacement therapy in
      adults were published. Since then, accumulated experience has shown a great
      individual variability in the response to GH replacement, including a potential
      difference in responsiveness between genders. The aim of this paper is to review
      the data regarding the effects of gender differences on GH pharmacokinetics,
      pharmacodynamics, and efficacy of replacement. In addition, we start with a short
      review of the possible role of GH in sexual development and sexual life.

PMID- 11527088
TI  - The somatomedin hypothesis revisited in a transgenic model.
AB  - Studies of insulin-like growth factor I (IGF-I) gene knockout mice models have
      clearly shown that IGF-I is necessary for prenatal as well as postnatal body
      growth in mice. Clinical studies of a patient with an IGF-I gene defect which
      caused complete absence of IGF-I, verified that it is important for intrauterine
      and postnatal growth. Recent studies of mice with liver-specific and inducible
      IGF-I gene knockout indicated that liver-derived IGF-I is not necessary for
      postnatal body growth, although serum IGF-I levels are decreased by more than 80%
      in these mice. Therefore, extrahepatic IGF-I is sufficient for maintenance of
      postnatal body growth in mice. Further investigations are needed to assess
      whether liver-derived circulating IGF-I is essential for other biological
      functions.

PMID- 11527089
TI  - Modulation of retinal endothelial cell behaviour by insulin-like growth factor I
      and somatostatin analogues: implications for diabetic retinopathy.
AB  - Evidence suggests the involvement of growth hormone (GH), insulin-like growth
      factor I (IGF-I) and somatostatin in the pathology associated with diabetic
      retinopathy. We examined the effect of IGF-I on human retinal endothelial cell
      (HREC) survival following high glucose exposure and serum starvation, examined
      the signalling pathways mediating the protective effect of IGF-I on HREC, and
      characterized somatostatin receptor-induced retinal endothelial cell death. IGF-I
      (10 ng/ml) protected HREC from apoptosis induced by high glucose and serum
      starvation. Wortmannin, a specific inhibitor of phosphotidylinositol-3-kinase,
      blocks the ability of IGF-I to protect HREC from apoptosis. Incubation of HREC in
      serum-free medium caused a time-dependent increase in c-Jun N-terminal kinase
      (JNK) activity, and continuous culture of HREC in the presence of IGF-I or
      vascular endothelial growth factor (VEGF) prevented JNK activation and arrested
      apoptosis. Activation of tyrosine kinase receptors results in extracellular
      signal-related kinase (ERK) activation and activation of ERK is required for
      proliferation. Both IGF-I and VEGF produced a time- and concentration-dependent
      increase in the activation of ERK. Type 2 and type 3 somatostatin receptors have
      been implicated in cell-cycle arrest and apoptosis. Activation of the type 3
      receptor in HREC resulted in cell death. These studies suggest that IGF-I is
      critical for HREC survival, and that somatostatin analogues acting through the
      type 3 receptor have direct effects on retinal endothelial cells. Furthermore, it
      appears that the therapeutic efficacy of somatostatin analogues lies not only in
      systemic inhibition of GH, but also in modulating local growth factor effects.

PMID- 11527090
TI  - Findings and theoretical considerations on the usefulness of the acid-labile
      subunit in the monitoring of acromegaly.
AB  - Growth hormone (GH) action induces a variety of biochemical factors of which
      insulin-like growth factor I (IGF-I) is conventionally measured for the diagnosis
      and monitoring of GH-related disorders such as GH deficiency or acromegaly. IGF-I
      circulates predominantly as a ternary complex with IGF-binding protein 3 (IGFBP
      3) and the acid labile subunit (ALS). In the treatment of active acromegaly with
      the GH receptor antagonist pegvisomant, ALS showed a closer correlation with the
      change in ring size, measured as a clinical indicator of disease activity, than
      did IGF-I or IGFBP-3. ALS thus seems to be a clinically useful marker of disease
      activity in acromegaly.

PMID- 11527091
TI  - Is there a medical need to explore the clinical use of insulin-like growth factor
      I?
AB  - Cloning of the insulin-like growth factor I (IGF-I) gene led to the development
      in 1987 of recombinant IGF-I available for clinical use. Trials were started
      targeting endocrine, metabolic and neurological disorders, and beneficial results
      have been demonstrated in IGF-I deficiency states caused by IGF-I gene deletion
      and growth hormone (GH) receptor deficiency, type 1 and type 2 diabetes mellitus,
      and severe insulin resistance syndromes. Results of equivocal benefit have also
      been reported in osteoporosis and amyotrophic lateral sclerosis. Recent
      encouraging data using the IGF-I-IGF-binding protein 3 (IGFBP-3) complex in
      diabetes mellitus suggest that this preparation may eventually replace
      recombinant free IGF-I. The lack of an established therapeutic indication for IGF
      I has resulted in its supplies being severely limited. It will probably be
      decided during the next decade whether use of IGF-I or the IGF-I-IGFBP-3 complex
      becomes firmly established as an accepted endocrine therapy.

PMID- 11527092
TI  - Growth hormone and exercise: physiology, use and abuse.
AB  - This review summarizes the interactions between growth hormone (GH) and exercise.
      Exercise has profound effects upon the GH-insulin-like growth factor I axis per
      se. In addition, there is increasing evidence that such physiological
      perturbations might be influential in the performance responses to repeated
      training. However, the ergogenic effects of systemic administration of
      recombinant human GH by athletes and bodybuilders remain unproven. What is
      certain is that the prevalence of GH abuse by sportspeople will increase, not
      least because it is currently undetectable. The frequent and potentially severe
      side-effects associated with such 'doping' will be of increasing relevance to
      endocrinologists.

PMID- 11527093
TI  - Obesity: a rational target for managing diabetes mellitus.
AB  - Obesity is a growing public health problem worldwide. It is a particularly common
      problem among individuals with type 2 diabetes mellitus. The magnitude of
      obesity, the central location of fat, and a history of weight gain are
      independent risks for developing diabetes mellitus. Potential factors implicated
      in the pathogenesis of diabetes mellitus in obese patients include increased
      plasma free fatty acid concentrations, increased production of cytokines,
      increased leptin levels, and increased levels of a recently discovered protein
      called resistin. Epidemiological and interventional studies suggest that even
      modest loss of body weight, either by changes in lifestyle or pharmacological
      means is associated with significant amelioration of insulin resistance and
      improvement in diabetes mellitus control. Treatment of obesity is an important
      therapeutic goal in the management of patients with type 2 diabetes mellitus.

PMID- 11527094
TI  - The role of leptin and hypothalamic neuropeptides in energy homeostasis: update
      on leptin in obesity.
AB  - Leptin is an adipocyte-secreted hormone the serum levels of which reflect the
      amount of energy stored in adipose tissue as well as short-term energy imbalance.
      Serum levels of many cytokines and hormones also influence circulating leptin
      levels. Leptin binding to specific receptors in the hypothalamus results in
      altered expression of orexigenic and anorexigenic neuropeptides that regulate
      neuroendocrine function and energy homeostasis, and recent experimental evidence
      suggests that leptin plays an important role in the pathogenesis of obesity and
      eating disorders. Research that followed the discovery of leptin is significantly
      broadening our understanding of the mechanisms underlying energy homeostasis, the
      elucidation of which is expected to result soon in the development of new
      therapeutic approaches for obesity and eating disorders.

PMID- 11527095
TI  - Regulation of gonadotropin-releasing hormone release by cyclic AMP signalling
      pathways.
AB  - The frequency and amplitude of gonadotropin-releasing hormone (GnRH) pulses are
      tightly regulated for the maintenance of reproductive cycles. Pulsatile GnRH
      release was shown to be an intrinsic property of murine GT1 GnRH neurons, and
      primate placodal GnRH neurons. GT1 neurons show spontaneous action potentials
      that are associated with Ca2+ oscillations and hormone secretion. Increased
      cyclic AMP (cAMP) levels in GT1 neurons appear to stimulate GnRH release by
      activation of cAMP-gated cation (CNG) channels. Activation of the CNG channels
      correlated with increased neuron excitability and Ca2+ oscillations. Activation
      of protein kinase A is not necessary for cAMP-induced stimulation of GnRH
      secretion, but appears to activate negative feedback pathways. Potential negative
      feedback pathways may decrease cAMP levels by inhibiting adenylyl cyclase V, and
      activating the phosphodiesterase, PDE4D3. These stimulatory and inhibitory cAMP
      signalling pathways appear to regulate the excitability of the GT1 neurons, and
      may constitute a biological clock timing the pulsatile release of GnRH.

PMID- 11527096
TI  - Activation of the hypothalamic-pituitary-adrenal axis in obesity: cause or
      consequence?
AB  - Cortisol secretion rate is increased in obesity, but plasma cortisol levels are
      not consistently elevated. This suggests that the principal abnormality in
      obesity may relate to enhanced peripheral metabolism. Recent studies have
      identified enhanced inactivation of cortisol by 5alpha-reductase, and impaired
      regeneration of cortisol in the liver by 11beta-hydroxysteroid dehydrogenase type
      1 (11beta-HSD1), as possible mediators of this increased cortisol clearance rate
      in obesity. Most intriguingly, the changes in 11beta-HSD1 are tissue-specific,
      and generation of cortisol from inactive cortisone appears to be increased in
      adipose tissue in obesity. Selective inhibition of 11beta-HSD1 provides a novel
      therapeutic target for lowering intra-adipose cortisol concentrations and effect,
      without inducing other adverse effects of cortisol deficiency.

PMID- 11527097
TI  - Visceral obesity and the role of the somatotropic axis in the development of
      metabolic complications.
AB  - It is well recognized that aberrant fat localization such as visceral obesity
      rather than total body fat mass is a major risk factor for cardiovascular disease
      and type 2 diabetes mellitus. During recent decades, several studies have
      described a range of metabolic disturbances associated with abdominal obesity,
      including glucose intolerance, hyperinsulinaemia, insulin resistance,
      hypertension and dyslipoproteinaemia, now widely known as the metabolic syndrome.
      Several abnormalities in the hypothalamic-pituitary axis have been described
      associated with visceral obesity, suggesting a central neuroendocrine
      dysregulation including increased cortisol concentration and impaired
      gonadotropin and growth hormone (GH) secretion. Some steps in the chain of events
      in this theory still remain unclear, however, although these findings have
      introduced new therapeutic possibilities. These include therapy with sex steroids
      in both viscerally obese men and women, and several attempts to use GH to treat
      the endocrine abnormalities present in visceral obesity. The results of these
      studies are promising, but the therapies are still not recommended for general
      use.

PMID- 11527098
TI  - The emotional consequences of false positive mammography: African-American
      women's reactions in their own words.
AB  - High false positive rates associated with screening for breast cancer in the
      United States have an unintended psychological consequence for women (Lerman et
      al., 1991) that has raised concerns in recent years (Sox, 1998). This study uses
      inductive qualitative analysis of open-ended interviews with 45 African American
      women living in New York City who were part of a larger study of women and their
      experiences after receiving an abnormal mammogram. Themes resulting from the
      analyses included: inadequate provider-patient communication, anxieties
      exacerbated by waiting and wondering, and fears of iatrogenic effects of follow
      up tests such as biopsies and repeat mammograms. While more research is needed on
      message-framing strategies for women entering mammographic testing and follow-up,
      modest changes in service delivery such as improved medical communication can
      help to alleviate fears and enhance trust.

PMID- 11527099
TI  - Daughters and mothers exercising together (DAMET): a 12-week pilot project
      designed to improve physical self-perception and increase recreational physical
      activity.
AB  - This paper presents the results of a 12-week single-sex, family-based physical
      activity intervention grounded in Social Cognitive Theory. Mother/daughter pairs
      and triads (n = 20) attended physical activity and classroom sessions twice
      weekly. Physiological data (VO2peak, height, and weight), psychological data
      (physical self-perception profile subscale scores), information about physical
      activity participation (PAP, d x wk(-1)) and qualitative impressions (QI) of the
      program were collected pre- and post-intervention. PAP and QI were also collected
      6-months after completing the intervention. Although no significant increases in
      physical activity were reported, significant improvements in perceived sport
      competence, physical condition, and strength and muscularity were reported over
      time. The social cognitive theory, as used to plan this physical activity
      intervention, offered a promising theoretical perspective for facilitating
      improved physical self-perception in adolescent girls and their mothers.

PMID- 11527100
TI  - Reproductive and contraceptive attitudes as predictors of condom use among women
      in an HIV prevention intervention.
AB  - This study prospectively evaluates the effect of childbearing motivation and
      contraceptive attitudes on consistency of condom use among at-risk women enrolled
      in an HIV prevention intervention. Women (age 15-40, 85% African-American) were
      recruited from homeless shelters, drug treatment facilities, and public housing
      developments and assigned to standard or enhanced intervention conditions. Among
      the eligible study group of nonsterilized women with a main partner (n = 312),
      24.4% wanted to have a baby at baseline; 43.5% believed their partner wanted them
      to have a baby. Women who reported a desire for a baby, compared to all others,
      were less likely to be at a higher level of condom consistency six months later
      (OR = 0.66; .48-.90). Women who perceived partner support for contraceptive use
      showed a higher level of condom consistency (OR = 1.20; 1.03-1.41) at 6-month
      follow-up. Many women in this study wanted to have a baby and this desire
      interfered with subsequent consistency of condom use. We also found that condom
      use increased toward consistency of use among women whose partner supported
      contraceptive use. HIV prevention interventions should include screening for
      reproductive motivation, so that prevention messages can be tailored to the
      realities of women's lives. Women who want a baby can be educated about disease
      prevention in the context of pregnancy planning and linked with appropriate
      services. Women who want to avoid childbearing can be given messages that
      emphasize the contraceptive benefits of condom use and that help strengthen
      partner support.

PMID- 11527101
TI  - Urban women's negotiation strategies for safer sex with their male partners.
AB  - Heterosexual transmission of HIV is growing at an increasing rate. One primary
      prevention strategy is to consistently use condoms. With the exception of female
      condoms, women do not "wear" condoms and therefore must negotiate condom use with
      their male partners. This present study examines the strategies women believe
      they would use in a safer sex negotiation with a male partner including (1)
      initiating negotiations, (2) resolving conflict, and (3) maintaining the
      intention to practice safer sex. The findings highlight the importance of
      understanding women's patterns of negotiation as well as their repertoire of
      negotiation skills prior to their exposure to behavioral interventions and
      prevention programs.

PMID- 11527102
TI  - Homeless women's access to health services: a study of social networks and
      managed care in the US.
AB  - Homeless women experience more severe physical and mental health problems than
      women in the general population. Under-utilization of health services complicates
      these health conditions. The study reported here explored how homeless women
      access health services within the context of shelter living and emerging managed
      care systems. Informed by grounded theory and dimensional analysis, the
      investigator conducted in-depth interviews with 19 homeless women, 6 staff from
      agencies serving homeless women, and 2 community health nurses. Findings revealed
      that homeless women usually had circuitous rather than direct routes to health
      services. First, they typically found a social network opportunity structure
      where brokers could assist them into the health care system. The first tiers of
      access included a domestic violence shelter, a shelter for single homeless women,
      and a cafe offering low-cost meals to an inner city homeless population. Even
      after locating this opportunity structure, the conditions of managed care, with
      its mechanisms of referral and unfamiliarity with the needs of impoverished
      women, complicated access. Thus, access requires policies that address not only
      the availability of health professionals, but also tiers of access that include a
      social network opportunity structure where women can interact with advocates who
      broker their entry into the health care system.

PMID- 11527103
TI  - The impact of family history of breast cancer on women's health beliefs, salience
      of breast cancer family history, and degree of involvement in breast cancer
      issues.
AB  - Prior investigations have employed the Health Belief Model (HBM) to predict
      health care utilization and cancer screening behaviors. The HBM is expanded in
      the current investigation to include issue involvement with breast cancer and
      salience of breast cancer family history. Differences in the constructs of this
      expanded HBM, as they relate to mammography screening, between women with
      positive and negative family histories of breast cancer were assessed in 378
      women. Perceived benefits and barriers were found to be similar for women with
      positive and negative family histories of breast cancer. However, susceptibility,
      cues to action, salience of family history, and issue involvement were found to
      be more relevant for women with a positive family history of breast cancer. These
      findings have implications for interventions directed at increasing compliance
      with recommendations for breast cancer screening.

PMID- 11527104
TI  - Gender differences in causes of depression.
AB  - This study adopts a stress process perspective to analyze gender differences in
      the causes of depression. The stress process links psychological well-being to
      position in the social structure via the mediating and moderating effects of
      stressors and resources. The study examines stressors and resources as mediators
      of the SES/depression relationship, and resources as moderators of the
      stressor/depression relationship. Furthermore, it tests the hypotheses that women
      are more exposed and more vulnerable to stressors than are men, that women
      benefit more psychologically from socially supportive relationships, and suffer
      more from conflict-ridden relationships than men. The analysis utilizes survey
      data of urban Nevadans age 45-74, collected in the Fall of 1997, and employs
      ordinary least squares regression to test the stress process model. The results
      indicate that financial strain and perceptions of danger in one's neighborhood
      mediate the relationship between SES and depression, but resources do not
      moderate the effects of stressors on depression. Women are more exposed to
      stressors than men, but are not more vulnerable to them. Positive social
      relationships do have more beneficial psychological effects for women than for
      men, but the effects of marital conflict do not vary by gender. Implications for
      social policy and treatment for depression are discussed.

PMID- 11527106
TI  - Beliefs and behaviors about Pap and breast self-examination among Thai immigrant
      women in Brisbane, Australia.
AB  - Regular screening is an important preventive method in reducing morbidity and
      mortality from cervical and breast cancer. In 1998, a cross-sectional study was
      conducted in Brisbane, Australia, among 145 Thai immigrant women, to explore
      cultural and social factors related to their use of Pap smear tests and breast
      self-examination (BSE). The study aimed at describing women's beliefs and
      perceptions about the body, breast and cervical cancer, and their perceptions of
      the causes of the diseases. It explored the women's perception of the severity
      and the effects of both cancers on aspects of patients' lives, and their chance
      of developing both cancers. The Thai immigrant women explained the causes of
      breast and cervical cancer using both traditional beliefs and medical knowledge.
      They perceived that both cancers affect a patient's health and her daily
      activities. Some women believed that they would develop cervical cancer if their
      perineum or vulva was "dirty." Some believed that they would have breast cancer
      because they had a history of benign tumor or cyst of a breast. Forty-four
      percent of the women had biennial Pap smears in the past five years and only 25%
      conducted BSE monthly in the past two years. Information relating to perceived
      barriers to undertake regular cervical cancer and breast cancer screenings and
      other health beliefs can be applied by health care personnel to increase Thai
      immigrant women's preventive health behaviors.

PMID- 11527105
TI  - Cervical cancer screening in ethnocultural groups: case studies in women-centered
      care.
AB  - INTRODUCTION: The purpose of this study was to identify and describe critical
      elements of women-centered care within the context of providing cervical
      screening to three ethnocultural groups in Canada: Asian, South Asian and First
      Nations. METHODS: Data for this collective case study included open-ended
      interviews with purposive samples of women and key informants from each target
      group. Following thematic analysis, cross-case analysis was completed by
      comparing and contrasting issues and contextual factors influencing women's and
      providers' experiences. RESULTS: Cervical screening services for each group were
      shaped by attention to ethnocultural values, women's desire for thorough
      explanations, and the importance of a comfortable setting. While participation
      rates varied across clinics, women were positive about their experiences in
      obtaining cervical screening. Some women's expectations that they could address a
      range of health concerns with female health providers at the clinics were stymied
      by structural barriers that prevented staff from addressing issues beyond those
      directly related to cervical screening. Cross-case analysis revealed three key
      elements of women-centered care: respectful and culturally appropriate
      interactions between women and health providers, the importance of providing
      acceptable alternatives for women, and the need for comprehensive health
      services. CONCLUSION: While the establishment of Pap test clinics for
      ethnocultural groups has the potential to enhance participation in cervical
      screening, changes in health policy and the structure of health services are
      required for existing programs to fully implement the elements of women-centered
      health care identified in this study. Other models of providing health care to
      women in ethnocultural groups, including the use of clinics staffed by nurse
      practitioners, should be evaluated.

PMID- 11527107
TI  - Single parenthood, occupational drift and psychological distress among immigrant
      women from the former Soviet Union in Israel.
AB  - BACKGROUND: The study examined whether the combination of single parenthood and
      occupational drift in the context of immigration puts single mothers at higher
      risk for psychological distress compared to married mothers, and investigated the
      potential mediating and moderating psychosocial factors (social support, sense of
      coherence-SOC, fluency in Hebrew). METHODS: Participants were selected from
      random samples of married and unmarried mothers, recent immigrants to Israel from
      the Former Soviet Union, aged 25-50 years. A total of 221 single mothers and 241
      married mothers were interviewed. RESULTS: No differences were found in
      occupational drift or in fluency in Hebrew between the groups. The levels of SOC
      and social support were significantly lower among the single mothers and mean
      scores of distress were significantly higher among single (1.48 +/- 0.75)
      compared to married mothers (1.21 +/- 0.65, p < 0.001). In multiple linear
      regressions on distress, no interaction of marital status and occupational drift
      was found. After inclusion of psychosocial variables, the association of marital
      status with distress was significantly mediated by SOC and more modestly by
      social support, and was moderated by social support: the beneficial effect of
      social support on distress was significantly greater for married mothers than for
      single mothers. CONCLUSIONS: The difference in psychological distress between
      single and married mothers during the first years after immigration is not due to
      occupational stressors but to psychosocial resources. Single parenthood should be
      viewed as a marker of psychosocial risk among immigrant women.

PMID- 11527108
TI  - Impact of job characteristics on psychological health of Chinese single working
      women.
AB  - This study aims at investigating the impact of individual and contextual job
      characteristics of control, psychological and physical demand, and security on
      psychological distress of 193 Chinese single working women in Hong Kong. The
      mediating role of job satisfaction in the job characteristics-distress relation
      is also assessed. Multiple regression analysis results show that job satisfaction
      mediates the effects of job control and security in predicting psychological
      distress; whereas psychological job demand has an independent effect on mental
      distress after considering the effect of job satisfaction. This main effect model
      indicates that psychological distress is best predicted by small company size,
      high psychological job demand, and low job satisfaction. Results from a separate
      regression analysis fails to support the overall combined effect of job demand
      control on psychological distress. However, a significant physical job demand
      control interaction effect on mental distress is noted, which reduces slightly
      after controlling the effect of job satisfaction.

PMID- 11527109
TI  - Pharmacology of beta-blockers: classical aspects and recent developments.
AB  - All clinically used beta-blockers share the common feature of being competitive
      antagonists at beta-adrenoceptors. They differ, however, in additional
      pharmacological properties, such as beta1/beta2-selectivity ratios, presence or
      absence of intrinsic sympathomimetic activity (ISA), and/or local anesthetic
      activity. Furthermore, beta-blockers differ widely in their pharmacokinetic
      properties. The mammalian beta1- and beta2-adrenoceptors are the products of
      different genes but the receptor proteins show a certain degree of homology. Both
      span the cell membrane seven times. The cytoplasmic part of the receptor protein
      is the site of phosphorylations and hence involved in the process of receptor
      internalization. Upon exposure of tissues or organs to beta-blockers,
      characteristic changes emerge at the cellular level. There is an increase in the
      density of beta-adrenoceptors in the surface membrane, termed upregulation. This
      upregulation is subtype-specific, i.e., nonselective beta-blockers increase the
      density of both beta1- and beta2-adrenoceptors whereas beta1-selective
      antagonists upregulate only the former subtype. In contrast, beta-blockers with
      pronounced ISA downregulate beta-adrenoceptors. Beta-adrenoceptor density also
      changes in pathological situations. There is a downregulation of cardiac beta
      adrenoceptors in dilated cardiomyopathy, probably as a consequence of increased
      sympathetic tone. A rapid upregulation of beta-adrenoceptors is characteristic of
      myocardial ischemia. This upregulation occurs in spite of a massive release of
      norepinephrine from cardiac adrenergic nerves during ischemia. Both
      norepinephrine release and upregulation of cardiac beta-adrenoceptors lead to an
      adrenergic overstimulation of ischemic myocardium. Blockade of beta-adrenoceptors
      inhibits the catecholamine component of this vicious circle and may explain part
      of the beneficial effects of beta-blockers in coronary artery disease and
      myocardial infarction.

PMID- 11527110
TI  - Optimization of beta-blockers' pharmacology.
AB  - Beta-adrenergic-blocking drugs (BABs) have a firm place in the therapy of
      cardiovascular conditions including angina and hypertension. Although all BABs
      are competitive inhibitors of beta-receptors, they may differ in their additional
      pharmacodynamics, i.e., beta1-(cardio)selectivity, partial agonistic activity
      (PAA), and pharmacokinetic properties. Understanding these additional properties
      would allow the physician to choose the more appropriate agent for some patients
      or for specific situations. beta1-Selective BABs may be of potential importance
      in patients with obstructive airway disease, peripheral vascular disease, and
      hyperlipidemia and in diabetic patients receiving antidiabetic drugs. These BABs
      may better control the increased blood pressure in response to hypoglycemia,
      exercise, or cigarette smoking. Nonselective BABs may be preferably used to
      decrease epinephrine-induced hypokalemia or to prevent myocardial infarction, and
      in certain circumstances (i.e., migraine, anxiety, thyrotoxicosis or essential
      tremor). BABs with PAA may theoretically cause a lesser degree of
      cardiodepression (reduction of heart rate at rest, cardiac output, and AV
      conduction), bronchospasm, and peripheral vasoconstriction and minor effects on
      plasma lipids. Withdrawal syndrome may be absent after BABs with PAA. The
      pharmacokinetic properties of the BABs such as absorption, bioavailability,
      elimination half-life, liver metabolization, interindividual variability, as well
      as pharmacological interactions depend on their hydrophilic/lipophilic ratio. The
      development of new BABs continues. It has been possible to incorporate into a
      drug molecule combinations of PAA, preferred beta1-blockade, and beta2-agonist
      activity. Even if these new agents cause less adverse effects (e.g.,
      vasoconstriction, bronchospasm), their clinical significance remains to be
      established.

PMID- 11527111
TI  - Circadian variation of the total ischemic burden and influence by beta-blocking
      agents.
AB  - We investigated 150 unselected patients with proven coronary artery disease. All
      patients were off all routine antianginal treatments and there were 598 ischemic
      episodes, of which 75% were silent. It was found that episodes of ischemia, both
      silent and painful, occurred predominantly during the daytime hours from 0730 to
      1930 h. This pattern is similar to that described by others. There was a
      significant excess of episodes of ischemia in the morning hours (0730-1330 h),
      with a secondary peak occurring in the evening hours. We further investigated a
      subgroup of 41 patients who were monitored for 1,581 h while being treated with
      atenolol. These patients were investigated in a double-blind fashion, and during
      the off treatment phase the circadian pattern of ischemic episodes was similar to
      that described for the group as a whole. However, on treatment with atenolol,
      there was a significant reduction in the frequency and total duration of ischemic
      episodes throughout the day. Atenolol significantly altered the circadian
      distribution of ischemic episodes with elimination of the morning peak; there was
      some preservation of the evening peak although this was smaller than that
      described when the patients were off therapy. The circadian distribution of
      ischemic episodes and the observed changes with beta-blocking treatment resemble
      the reported circadian variation of acute myocardial infarction and sudden death.
      Although these studies do not in any way prove that myocardial ischemic episodes
      and their alteration by treatment are related to the development of acute
      myocardial infarction and death, the relationship between ischemic episodes and
      the end points of coronary disease require further investigation.

PMID- 11527112
TI  - The role of catecholamines in ischemia.
AB  - In myocardial ischemia, sympathetic activity of the heart is closely connected
      with the progression of cell injury and the incidence of malignant arrhythmias.
      Adrenergic stimulation of the ischemic myocardium is due to increased local
      norepinephrine concentrations in the heart, whereas the plasma catecholamine
      levels are of minor relevance. During the first few minutes of ischemia. efferent
      sympathetic nerves are activated. Excessive accumulation of norepinephrine,
      however, is prevented since adenosine, formed in the ischemic myocardium,
      suppresses exocytotic norepinephrine release, and released norepinephrine is
      rapidly removed as long as catecholamine reuptake is functional. With progression
      of ischemia to more than 10 min, the myocardium is no longer protected against
      excess catecholamine accumulation in the interstitial space because local
      metabolic release mechanisms become increasingly important. This release, which
      is independent of central sympathetic activity and extracellular calcium, occurs
      in two steps: first, norepinephrine escapes from its intracellular storage
      vesicles and accumulates in the cytoplasma of the neuron; in a second, rate
      limiting step, norepinephrine is transported across the plasma membrane into the
      interstitial space, using the neuronal uptake carrier in reverse of its normal
      transport direction. Studies using acute and chronic sympathetic denervation and
      antiadrenergic agents demonstrate that this local metabolic, rather than
      centrally induced, norepinephrine release is critically involved in the
      progression of ischemic cell damage and the occurrence of ventricullar
      fibrillation in early ischemia. As a consequence of local metabolic catecholamine
      release, extracellular norepinephrine reaches 1,000 times the normal plasma
      concentration within 20 min of ischemia. Myocardial ischemia results in a
      temporary supersensitivity to catecholamines of the myocytes. This is due to a
      twofold increase in alpha1- and a 30% increase of beta-adrenergic receptor number
      at the cell surface. The sensitization of adenylate cyclase during the first 20
      min of total ischemia is followed by a rapid inactivation of the enzyme that also
      includes the coupling protein Gs. The deleterious combination of extremely high
      norepinephrine concentrations with an at least temporarily enhanced
      responsiveness of the tissue to catecholamines is thought to accelerate the
      propagation of the wavefront of irreversible cell damage in the ischemic
      myocardium. Moreover, the inhomogenous distribution of catecholamine excess
      within the heart is considered to promote malignant arrhythmias by unmasking and
      enhancing electrophysiological disturbances in early ischemia.

PMID- 11527113
TI  - Medical interventions in acute myocardial infarction.
AB  - Streptokinase, APSAC, and rtPA clearly reduce mortality in acute myocardial
      infarction. rtPA is definitely superior at recanalization; it does it faster and
      more effectively in the first 1-2 h after infusion. There is no evidence that it
      causes less bleeding, but rather that the proneness to bleeding might be a little
      higher. rtPA is expensive. Therefore, on the whole, physicians in the United
      Kingdom mainly use streptokinase and some APSAC. rtPA is probably the best agent
      for second-time use within 6-12 months of the first use of streptokinase or
      APSAC, when antibodies may limit the effectiveness of these agents. Aspirin is
      clearly useful, and one should remember to use it long term in any patient who
      has had a vascular event. It should not be used for primary prevention except
      where there is a clear vascular risk. For secondary prevention, it is very
      effective. Intravenous beta-blockers should be considered for less ill patients,
      who amount to about 50% of all patients admitted. Beta-blocker treatment reduces
      cardiac rupture and should be used in conjunction with thrombolysis and continued
      long term in patients without contraindications. It also has proven
      antiarrhythmic benefit (sudden death). Anticoagulants are promising but yet to be
      proven. Nitrates may have a place in the acute therapy of myocardial infarction,
      but calcium blockers and lidocaine are definitely not suited for routine use.
      Lidocaine should generally be used only in patients who already have ventricular
      fibrillation or severe or symptomatic ventricular arrhythmia. Finally, before
      getting too enthusiastic, one should remember that this overview deals only with
      those people who reach the hospital alive. There is a huge number of patients at
      least equal to those admitted who die before reaching medical help. They have to
      be prevented from getting a myocardial infarction. Therefore, along with better
      treatment, we need to focus on prevention, with arguments against smoking, excess
      weight, and in favor of more exercise. These arguments are still very important.

PMID- 11527114
TI  - Invasive strategy for treatment of myocardial infarction.
AB  - The classical approach to the treatment of acute myocardial infarction (MI) has
      been one of stabilization and complication management. In an effort to optimize
      treatment, the initiation of the cardiac care unit and the use of antiarrhythmic
      therapy have succeeded in lowering the mortality rate substantially. More modern
      concepts are aimed at limiting infarct size and preserving myocardial function.
      These aims can be achieved medically using intravenous (i.v.) thrombolysis or
      invasively either with intracoronary (i.c.) thrombolysis, percutaneous
      transluminal coronary angioplasty (PTCA), or bypass surgery. Although i.c.
      thrombolysis is more effective than the i.v. route, the necessity for acute
      coronary catheterization makes it incompatible and difficult for routine use, and
      thus is usually reserved for cases in which i.v. lysis has failed. Intravenous
      thrombolysis is becoming the standard approach to MI, and the remaining questions
      are those of which drug and dosage are optimal and how to approach the patient
      after thrombolysis. In this regard, we favor a symptom-guided approach, as shown
      by the TIMI-IIA and European cooperative studies. In patients with ongoing
      ischemia postlysis, heart catheterization is indicated and a decision regarding
      PTCA or surgery is then made, depending on anatomy. In patients remaining stable
      after acute lysis, a predischarge stress may help in selecting patients requiring
      catheterization. As an alternative invasive approach to acute MI, PTCA may be the
      quickest and most effective method to recanalize a vessel, but, again, logistical
      problems make it incompatible in the acute setting. The same is true for bypass
      surgery, and although extensive improvements have been made in intraoperative
      myocardial preservation so that a 2% mortality is achievable, it is reserved for
      patients with extensive ischemia and anatomy unsuitable for PTCA (extensive
      multivessel or left main disease).

PMID- 11527115
TI  - Safety and efficacy of beta-blockers in the treatment of stable angina pectoris.
AB  - In stable exercise-induced angina pectoris, beta-blockers exert their beneficial
      effects mainly through a reduction in heart rate, blood pressure. and
      contractility. Additional beneficial effects are an improvement in myocardial
      oxygen supply through a redistribution of coronary flow, a lengthening of
      diastole, a facilitation of aerobic metabolism, and a rightward shift of the
      oxygen-hemoglobin dissociation curve. Cardioselective beta-blockers can be
      expected to have fewer side effects than the nonselective drugs. Apart from a
      reduction in anginal attack rate and an improvement in exercise capacity, a
      reduction in silent ischemia may be desirable when treating patients with stable
      effort angina, beta-blockers effectively reduce asymptomatic ischemia. Bisoprolol
      is a new beta1-selective beta-blocker with a clear 24-h duration of action
      regarding symptoms and improvement of exercise capacity in patients with stable
      exercise-induced angina pectoris. Bisoprolol 10 mg and atenolol 100 mg are
      equipotent in achieving these effects.

PMID- 11527116
TI  - Beta-blocking agents in heart failure: modern concepts and overview.
AB  - Heart failure is characterized by the inability of the myocardium to shorten
      sufficiently or to eject an adequate stroke volume to maintain normal perfusion
      of both the cardiac and the extracardiac organs. Irrespective of etiologic
      reasons, the depression of myocardial contractility represents one of the major
      mechanisms that contributes to low output in heart failure. Despite their
      intrinsic negative inotropic effects, beta-receptor-blocking agents have been
      used in numerous studies for treating the failing heart, especially in dilated
      cardiomyopathy and ischemic heart disease. In this regard, specific therapeutic
      aims of the use of beta-receptor-blocking agents in chronic heart failure have
      been described. e.g., reduction of an increased heart rate in tachycardia, blood
      pressure reduction in hypertensive heart failure, improvement of supraventricular
      and ventricular arrhythmias, depression of an increased sympathetic tone (e.g.,
      in hyperthyrioidism, pheochromocytoma), increase in the amount of downregulated
      beta-receptors, and anti-ischemic effects in coronary artery disease. For chronic
      heart failure, therefore, some special indications may be established and may be
      individually used; for acute heart failure, only very rare indications are
      present (e.g., hypertensive crisis, life-threatening cardiac arrhythmias). The
      actual rationale for the use of beta-receptor blocking agents in heart failure is
      therefore analyzed with regard to pathophysiology, clinical effects, and clinical
      outcome of treated patients.

PMID- 11527117
TI  - The role of cardiac beta1- and beta2-adrenoceptor stimulation in heart failure.
AB  - Substantial evidence has accumulated that in the human heart both beta1- and
      beta2-adrenoceptors coexist. As a rule, the amount of beta2-adrenoceptors is
      higher in the atria (about 30% of the total beta-adrenoceptor population) than in
      the ventricular myocardium (about 20%). Both beta1- and beta2-adrenoceptors
      couple to adenylate cyclase and mediate positive inotropic effects of
      isoproterenol and epinephrine on isolated, electrically driven cardiac
      preparations. In the atria, stimulation of both beta1- and beta2-adrenoceptors
      causes maximal increases in contractile force; in the ventricular myocardium,
      however, only beta1-adrenoceptor stimulation maximally increases contractile
      force, whereas beta2-adrenoceptor stimulation evokes only submaximal increases.
      On the other hand, norepinephrine induces its positive inotropic effect on atrial
      and ventricular preparations solely via beta1-adrenoceptor stimulation. Because
      norepinephrine is the main transmitter of the human sympathetic nervous system,
      this indicates that under normal physiological conditions, the heart rate and
      contractility are under the control of cardiac beta1-adrenoceptors, whereas
      cardiac beta2-adrenoceptors play only a minor role, if at all. However, in
      situations of stress, when large amounts of epinephrine (acting at both beta1-
      and beta2-adrenoceptors with the same affinity) are released from the adrenal
      medulla, activation of cardiac beta2-adrenoceptors may contribute to an
      additional increase in heart rate and/or contractility. In chronic heart failure,
      cardiac beta-adrenoceptor function decreases (presumably due to endogenous
      "downregulation" by the elevated catecholamines), and this decrease is related to
      the severity of the disease (judged clinically by NYHA functional class).
      However, cardiac beta1- and beta2-adrenoceptors seem to be differentially
      affected in different kinds of heart failure: in end-stage dilated
      cardiomyopathy, beta1-adrenoceptors selectively decrease, whereas beta2
      adrenoceptors are nearly normal. Under these (pathological) conditions, beta2
      adrenoceptors may substitute for the loss in beta1-adrenoceptors, thereby
      maintaining contractility, at least partially. On the other hand, in end-stage
      ischemic cardiomyopathy, tetralogy of Fallot, and mitral valve disease, both
      beta1- and beta2-adrenoceptors concomitantly decrease. The reason for this
      differential regulation of cardiac beta1- and beta2-adrenoceptors in different
      forms of heart failure remains to be elucidated.

PMID- 11527118
TI  - Beta-blocking agents and positive inotropic agents in the therapy of chronic
      heart failure.
AB  - Positive inotropic stimulation of the failing cardiac muscle seems to be useful,
      if certain requirements are met: (a) there is some cardiac contractile reserve
      left, (b) the positive inotropic agent of choice is able to mobilize this
      contractile reserve, and (c) peripheral vascular resistance is not increased
      permanently by this agent. On the other hand, the physiological response (i.e.,
      positive inotropic effect) to circulating catecholamines in heart failure is
      decreased or even absent due to receptor desensitization and an alteration of
      guanine nucleotide-binding proteins (increased Gi). It has been proved that
      functionally active beta-adrenoceptors may be restored by treatment with beta
      adrenoceptor antagonists. However, these agents necessarily will have negative
      inotropic effects in the failing cardiac muscle, if the force of contraction is
      largely dependent on a permanent stimulation by catecholamines and if there are
      no spare beta-adrenoceptors. To clarify these as-yet unresolved problems, we have
      determined the contractile reserve as well as its utilization by positive
      inotropic agents in human cardiac muscles of failing and nonfailing hearts. The
      number and functional activity of cardiac glycoside receptors, beta
      adrenoceptors, and alpha-adrenoceptors were measured as well as the positive
      inotropic and negative inotropic effects of partial agonists. Furthermore, we
      have accumulated evidence that, in fact, there are no spare beta-adrenoceptors in
      the human cardiac muscle. The lack of spare beta-adrenoceptors has consequences
      for the therapeutic approach in patients with heart failure. At least initially,
      the administration of beta-adrenoceptor-blocking agents to patients with heart
      failure depending on agonist-induced stimulation will lead to a worsening of
      cardiac function. If this situation can be tolerated, however, the subsequent
      restoration of functionally active beta-adrenoceptors after beta-blockade may
      lead to restored physiological regulation of force of contraction by
      norepinephrine.

PMID- 11527119
TI  - Beta-blockers vs. angiotensin-converting enzyme inhibitors in hypertension:
      effects on left ventricular hypertrophy.
AB  - Both beta-blockers and angiotensin-converting enzyme (ACE) inhibitors have been
      shown to cause left ventricular hypertrophy regression in hypertensive patients.
      So far, no study allowed a true comparison of these drugs in this regard.
      Therefore, 56 hypertensive patients (38 newly recognized and 18 without any
      antihypertensive drugs for more than 2 months, mean of 9.5+/-14 months) were
      randomized to enalapril (En, n = 30) or a beta-blocker, bisoprolol (Bi, n = 26),
      once daily and underwent before and after 2 and 6 months on treatment (a) office
      and 24-h ambulatory monitoring of BP, (b) M-mode echo assessment of left
      ventricular mass (LVM) index and fractional shortening (FS), and (c) Doppler
      evaluation of left ventricular filling. All recordings were read blindly by two
      observers. The intraobserver coefficient of variation of LVM was 9%. After 6
      months, office BP (146+/-18/90+/-10 vs. 170+/-14/104+/-8 mm Hg) and 24-h BP(120+/
      17/77+/-9 vs. 138+/-15/90+/-9 mm Hg) were similarly reduced with both drugs. The
      LVM index was significantly reduced (p < 0.001) (Bi, 11%; En, 7%) and FS was
      unchanged. The early to late diastolic left ventricular flow ratio (E/A) was
      increased with bisoprolol (1.06+/-0.29 vs. 0.85+/-0.17, p < 0.0001) but not with
      enalapril (0.95+/-0.24 vs. 0.88+/-0.34), but this was mainly due to heart rate
      reduction with bisoprolol. We found no correlation between the reductions in 24-h
      BP and in LVM index. Bisoprolol and enalapril were similarly effective in
      lowering blood pressure (BP) in the office and during 24-h monitoring and in
      reducing the left ventricular mass index in hypertensive patients.

PMID- 11527120
TI  - Beta-blocking agents vs. antiarrhythmic interventions in heart failure
      complicated by arrhythmias.
AB  - Approximately 40-50% of the patients with end-stage cardiac failure (either
      ischemic or nonischemic) die suddenly and unexpectedly, most probably from
      ventricular fibrillation. It is unclear whether the complex ventricular
      arrhythmias observed in large numbers of these patients were related to the mode
      of death. Theoretically, it seems quite reasonable to attempt to suppress the
      development of life-threatening ventricular arrhythmias (e.g., sustained
      ventricular tachycardia or ventricular fibrillation) in those patients. If
      antiarrhythmic drug therapy is ineffective, alternative antiarrhythmic
      interventions (antiarrhythmic surgery or implantation of an automatic implantable
      cardioverter defibrillator) should be considered. In patients with so-called
      potentially malignant ventricular arrhythmias (e.g., nonsustained ventricular
      tachycardia), antiarrhythmic drug therapy remains controversial as presently
      there is no definitive proof that this therapy prolongs life or reduces the
      incidence of sudden cardiac death. In patients with end-stage cardiac failure,
      beta-blockade can result in a decrease in resting tachycardia, improvement in
      clinical heart failure symptoms, and increase in work load capacity. It remains
      controversial whether treatment with these agents can also improve prognosis and
      prevent sudden cardiac death. Therefore, at this time, only patients in the
      earlier stages of this clinical syndrome and with clinical signs of markedly
      increased sympathetic tone can be treated with low doses of beta-blockers.

PMID- 11527121
TI  - Bisoprolol: studies of potential interactions with theophylline and warfarin in
      healthy volunteers.
AB  - Many patients receiving bisoprolol treatment might also require warfarin or
      theophylline therapy. Two studies were carried out in healthy volunteers to
      investigate the possibility that bisoprolol might interact with warfarin or
      theophylline, both of which have low therapeutic ratios. In a balanced, two-way,
      crossover study, eight men and four women took bisoprolol 10 mg daily for 14
      days. They were divided into two groups of six volunteers. On the tenth day of
      treatment, six subjects received theophylline 375 mg (Nuelin tablets) by mouth
      and the pharmacokinetics of theophylline were determined. After a washout period
      of 7 days, they also underwent determination of single-dose theophylline
      kinetics. The other six subjects had single-dose theophylline kinetics determined
      7 days before the first dose of bisoprolol, and then again after 10 days of
      bisoprolol treatment. Concurrent administration of bisoprolol did not influence
      the tolerability of theophylline and had no significant effect on any of the
      pharmacokinetic parameters for theophylline. In a separate study, 12 healthy men
      received warfarin daily until their prothrombin times were about 1.5 x control.
      They then received bisoprolol 10 mg daily p.o. for 10 days; warfarin was
      continued until 5 days after the end of bisoprolol treatment. Bisoprolol and
      warfarin treatments were well tolerated, and there was no effect on prothrombin
      times of either starting or stopping bisoprolol treatment. These studies show no
      effect of bisoprolol treatment upon theophylline pharmacokinetics, and no
      evidence of an effect of bisoprolol upon low-level anticoagulation with warfarin.
      Nevertheless, care should always be taken when changes are made in the medication
      of patients receiving theophylline or warfarin.

PMID- 11527122
TI  - Study of the electrophysiological properties of intravenous bisoprolol in
      patients with and without coronary artery disease by programmed stimulation.
AB  - The objective of this study was to assess the electrophysiological properties of
      intravenous bisoprolol in patients with and without coronary artery disease (CAD)
      by programmed stimulation. Sixteen inpatients subjected to an
      electrophysiological investigation because of dizziness or palpitations were
      given 10 mg of intravenous bisoprolol after basal measurement and were checked
      again 15 and 45 min after infusion. Eight patients with CAD (seven males and one
      female; mean age of 60+/-4 years) and eight patients without CAD (five males and
      three females; mean age of 59+/-4 years) were investigated after washout of prior
      antiarrhythmic drugs. For coronary patients, the CAD was documented by a history
      of myocardial infarction or by a confirmatory coronary arteriography. Main
      outcome measures were parameters of invasive electrophysiological exploration,
      with measurement of conduction intervals at rest and during pacing and of
      refractory periods by means of extrastimulus technique. No significant difference
      was noted at baseline between the two groups except for CSNRT. After infusion of
      10 mg of bisoprolol, with the exception of CSNRT (increased in the group without
      CAD), no significant differences were noted on comparison between coronary and
      noncoronary patients. Bisoprolol significantly increased the sinus cycle length,
      SACT, and FRP of the atria. Regarding atrioventricular nodal conduction,
      bisoprolol significantly increased the AH 100, ERP, and FRP and significantly
      decreased the Wenckebach point. In the right ventricle, bisoprolol moderately,
      but significantly, decreased the corrected QT and induced a small, temporary,
      significant increase in ERP. Bisoprolol appears to be a very potent beta-blocker
      that is well tolerated at an intravenous dose of 10 mg. Its depressant effects
      concern mainly the atrial function and the nodal conduction, without significant
      differences between the two groups of patients. The decrease in QTc may be a
      favorable aspect regarding its electrophysiologic tolerance especially in the
      acute phase of myocardial infarction.

PMID- 11527123
TI  - Three years of experience with bisoprolol in the treatment of mild to moderate
      hypertension.
AB  - Long-term efficacy and safety of the beta1-selective adrenoceptor-blocking agent
      bisoprolol was investigated in 164 patients with mild to moderate essential
      hypertension who had already been treated successfully with bisoprolol once daily
      for 1 year in preceding studies. The good therapeutic effect of bisoprolol was
      maintained for another 1 or 2 years. There was no need for further dose
      adaptations, and the patients remained on their individually titrated dose. At
      the end of the third year, 22.6% of the patients required 5 mg or less, 63.7%
      needed 10 mg, and 13.7% of the patients required 20 mg. Four patients received a
      diuretic in addition to maintain a reasonable blood pressure reduction. Thirty
      four of the 164 patients experienced adverse events, which necessitated a
      premature study withdrawal only in 2 cases. The repeatedly checked laboratory
      parameters did not adversely change under long-term treatment with bisoprolol up
      to 36 months. In particular, this also holds true for total cholesterol,
      triglycerides, and blood glucose.

PMID- 11527124
TI  - Effect of bisoprolol and acebutolol on resting blood pressure and on exercise
      blood pressure profile in hypertensive patients: a comparative, single-blind
      study.
AB  - The objective of this study was to compare the efficacy and the safety of
      bisoprolol (B) and acebutolol (A) on blood pressure at rest and during exercise
      in hypertensives. The design was a comparative, single-blind study with two
      phases following a 10-day washout period for pretreated patients: a 15 day
      placebo phase and an 8-week therapeutic phase. Forty-six outpatients suffering
      from mild to moderate essential hypertension [diastolic blood pressure (DBP)
      ranging between 95 and 120 mm Hg] were randomly given either 10 mg of bisoprolol
      or 400 mg of acebutolol once a day for 8 weeks; this dosage was doubled after 4
      weeks if DBP was still above 90 mm Hg. Blood pressure measurements were made 24 h
      after drug intake at rest and during exercise stress tests and were performed at
      the end of the placebo period and after 1 and 2 months of active treatment. Serum
      lipid levels were also measured before and at the end of the study. Forty-four
      patients (21 B/23 A) were analyzed for resting blood pressures and 33 (15 B/18 A)
      for exercise blood pressure profile. At the end of the first month of treatment,
      a significant decrease (p < 0.001) in supine and upright systolic (SBP) and DBP
      was noted in both groups. The reduction in supine DBP after 4 weeks was
      significantly greater with B (p = 0.036). A further decrease of blood pressure
      was observed in both groups during the second month of treatment, which was
      significant only in supine SBP (p < 0.05). After 2 months, the heart rate
      decreased by 24% with B and 13% with A (B vs. A; p = 0.002). Regarding the BP
      profile during exercise, B and A caused a similar and significant reduction in
      both SBP and DBP (p < 0.001). The reduction in heart rate during exercise was
      more marked with B, with no significant difference between the two groups. Side
      effects were reported in three patients on B and six on A. Both at rest and
      during exercise, at a level of effort similar to that of daily activities, B
      exerted a hypotensive effect at least equivalent to that of A in mild and
      moderate hypertensive patients.

PMID- 11527125
TI  - Age dependence of therapy result and risk in the treatment of arterial
      hypertension?
AB  - In an open multicenter study, 2,012 patients with mild to moderate essential
      hypertension were treated for 8 weeks with the beta1-selective blocker
      bisoprolol. A total of 570 general practitioners participated in this study. A
      total of 1,597 patients whose resting diastolic blood pressure (DBP) ranged from
      95 to 115 mm Hg were considered eligible for this study. Patients received one
      tablet of bisoprolol (5 mg) o.d. for the first 4 weeks. In patients not
      responding satisfactorily to treatment, the dose could be increased to 10 mg o.d.
      for the following 4 weeks. A total of 1,201 patients were evaluated for efficacy
      and all 2,012 patients were evaluated for tolerability. After 4 weeks of therapy,
      mean systolic blood pressure (SBP) was lowered significantly from 170+/-15 to
      151+/-14 mm Hg, and mean DBP was lowered from 104+/-5 to 92+/-7 mm Hg. A further
      4-week treatment lowered the blood pressure even more: mean SBP from 151+/-14 to
      144+/-13 mm Hg and mean DBP from 92+/-7 to 88+/-7 mm Hg. The total extent of both
      SBP and DBP reduction was equal in all age groups and showed no dependency of the
      initial blood pressure value. At the end of the study. the responder rate was
      94.9% in patients aged under 60 years, and 90.6% in patients aged over 60 years.
      The age group 31-40 years showed the highest responder rate (97.5%). After 8
      weeks of treatment, 69.5% of the patients were still on 5 mg of bisoprolol and
      27.6% on 10 mg of bisoprolol. Of all 2,012 patients, 11.6% reported side effects
      such as vertigo, fatigue. gastrointestinal disturbances, and headache. The
      incidence of adverse drug reactions was highest in the age group 31-40 years.
      Bisoprolol proved in this study to be an effective and safe antihypertensive
      agent when given to patients with mild to moderate hypertension for 8 weeks.

PMID- 11527126
TI  - Bisoprolol vs. chlorthalidone: a randomized, double-blind, comparative study in
      arterial hypertension.
AB  - The antihypertensive effect and tolerance of bisoprolol and chlorthalidone were
      evaluated in a randomized, double-blind, controlled trial during 4 weeks of
      treatment. A total of46 patients, aged 18-65 years, were initially included; 41
      patients presenting with a diastolic blood pressure between 95 and 120 mm Hg at
      the end of a previous placebo period completed the trial. They were randomly
      allocated to two groups: 22 patients were treated with bisoprolol 10 mg o.d., and
      19 patients with chlorthalidone 50 mg o.d. Both treatments induced a significant
      reduction in systolic and diastolic blood pressure (p < 0.001). No difference in
      antihypertensive efficacy was found between the two treatments after 4 weeks.
      However, with chlorthalidone, significant changes were found with regard to serum
      potassium (decrease; p < 0.001) and uric acid (increase: p < 0.05) and the
      incidence of clinical side effects was higher in the chlorthalidone group (37%)
      in comparison to the patients treated with bisoprolol (13%).

PMID- 11527127
TI  - Cardiovascular reactivity to and renal impact of stress and exercise: effects of
      bisoprolol.
AB  - The orthosympathetic nervous system is involved in the pathogenesis of essential
      hypertension. In this study, we carried out tests of sympathetic stimulation
      using successfully an isometric exercise and a psychological stress. The efficacy
      of the two tests in 10 normotensive patients (NTs) was assessed by a significant
      increase in blood pressure and heart rate and a significant increase in
      metanephrine urinary excretion. These tests, repeated 2 months later, were
      perfectly reproducible in NTs. The cardiovascular response during exercise and
      stress was significantly higher in 10 hypertensive patients (HTs) than in NTs. At
      rest, urinary norepinephrine excretion was significantly higher in HTs. In
      contrast to NTs, stress in HTs significantly increased urinary excretion of
      epinephrine and norepinephrine, whereas exercise failed to increase urinary
      catecholamine excretion in both groups. In HTs, both tests induced an increase in
      microalbuminuria. Among functional renal parameters, only proximal sodium
      reabsorption (measured by lithium clearance) was significantly lower in HTs than
      in NTs, compensated by a higher distal reabsorption. In HTs, 2 months of
      treatment with bisoprolol reduced rest and peak heart rate and blood pressure,
      but failed to reduce blood pressure reactivity to the orthosympathetic
      stimulation. Proximal sodium reabsorption at rest was normalized by the
      treatment. Bisoprolol was also able to reduce microalbuminuria during the 24 h
      and in the rest period preceding the test, but the same percent increase was
      observed during tests.

PMID- 11527128
TI  - Interaction of bisoprolol and procainamide in human cardiac impulse generation
      and conduction.
AB  - Combined treatment of beta-adrenoceptor-blocking agents and class I
      antiarrhythmic drugs can potentially have profound and deleterious effects on
      cardiac impulse formation and conduction. We studied the effect of 5 mg of oral
      bisoprolol daily and 10 mg/kg of procainamide intravenously with programmed
      electrical stimulation of the heart in 10 patients with postinfarction
      ventricular tachyarrhythmias. Oral bisoprolol slowed sinus rhythm and
      atrioventricular nodal conduction; ventricular effective refractory periods were
      increased significantly after several days of oral bisoprolol treatment. Combined
      treatment of oral bisoprolol and intravenous procainamide did not produce
      clinically relevant changes in parameters of cardiac impulse formation and
      conduction. This study shows that combined use of bisoprolol and a class I
      antiarrhythmic drug appears to be safe in patients with ventricular
      tachyarrhythrhythmias late after myocardial infarction.

PMID- 11527129
TI  - Bisoprolol pilot studies in myocardial infarction.
AB  - The efficacy of beta-blockade after myocardial infarction (MI) has been
      investigated in a series of studies. When beta-blockers are used during the first
      hours after the onset of MI, a reduction in infarct size, mortality, and nonfatal
      reinfarction may occur. Bisoprolol is a highly beta1-selective beta-blocker,
      without intrinsic sympathomimetic activity (ISA), and with a plasma elimination
      half-life of 10-12 h, permitting treatment with one daily dose. Because no
      experience with bisoprolol was available in MI, its safety and efficacy were
      studied in two open, uncontrolled pilot studies. The first study was a dose
      finding study in 37 patients with a 3-day-old MI. Bisoprolol was given
      intravenously and carefully titrated in steps of 1 mg up to a cumulative maximum
      dose of 5 mg. Subsequently, the patients received 10 mg of oral bisoprolol once
      daily (o.d.) until the end of the study. Based on the results of this first pilot
      study, a second pilot study was performed in which bisoprolol was given within
      the first 6 h after the onset of MI. Intravenous (i.v.) bisoprolol was titrated
      in two steps of 2.5 mg each, directly followed by 10 mg of oral bisoprolol o.d.
      The aim of this study was to investigate the influence of i.v. and subsequent
      oral bisoprolol on central hemodynamics. The results of these studies demonstrate
      that i.v. and subsequent oral administration of bisoprolol is well tolerated and
      indicate that the selected dose regimen is hemodynamically safe.

PMID- 11527130
TI  - Hemodynamics and exercise tolerance after bisoprolol, nifedipine, and their
      combination in patients with angina pectoris.
AB  - The different mechanisms of action of beta-blockers and calcium antagonists could
      result in an additive therapeutic effect in patients with angina pectoris. Twenty
      one male patients aged between 41 and 68 years and suffering from chronic stable
      angina pectoris and coronary artery disease confirmed by angiography took part in
      a randomized, double-blind study to examine the acute effect of 10 mg of
      bisoprolol, 20 mg of nifedipine, and a combination of the two drugs on
      hemodynamics at rest and during exercise [heart rate (HR), systolic blood
      pressure (SBP), rate-pressure product (RPP), cardiac index (CI), total peripheral
      resistance (TPR), and pulmonary capillary wedge pressure (PCP)], the behavior of
      the ST segment (ST), and exercise tolerance until occurrence of an ST-segment
      depression of 0.1 mV (W-ST01) and until onset of anginal pain (W-AP1). Following
      a baseline exercise test, 11 patients were given 10 mg of bisoprolol orally,
      whereas 10 patients received placebo. Two hours later, a second exercise test was
      carried out. All patients in both groups then received 20 mg of N orally. A third
      exercise test was performed 2 h later. On exercise, bisoprolol resulted in
      significant changes in HR (-16%), RPP (-22%), and CI (-16%), as well as in TPR (+
      13%); PCP was not significantly affected. Nifedipine led to significant changes
      in CI (+9%) and PCP (-34%). The effects of bisoprolol on HR and RPP and of
      nifedipine on PCP were retained in the combination. Competition was detectable as
      regards the opposing effects on CI and TPR. Measured by W-ST01 and ST, bisoprolol
      had a marked anti-ischemic effect, whereas that of nifedipine was distinctly
      less. There was an increase in effect after combination of the drugs (not
      significant). In patients with chronic angina pectoris due to coronary artery
      disease, bisoprolol and nifedipine had different hemodynamic profiles after acute
      administration; when the two drugs were combined, these effects were partly
      intensified and partly canceled out. There was a tendency for the effect of
      bisoprolol to be intensified by nifedipine in the combination. The combination of
      bisoprolol and nifedipine was well tolerated in the doses selected.

PMID- 11527131
TI  - Bisoprolol in the treatment of chronic stable angina pectoris.
AB  - The purpose of the study was to assess the efficacy and tolerance of the beta1
      selective beta-adrenoceptor-blocking agent bisoprolol in patients with chronic
      stable angina pectoris. A total of 236 outpatients (158 male and 78 female) over
      21 years of age (mean age of 57 years and 60 years for men and women,
      respectively) were included in an open trial of 4 weeks duration. A total of
      32.5% of the patients were smokers. After a washout period of at least 1 week,
      patients were initially treated with 10 mg of bisoprolol o.d. for 2 weeks, after
      which the dose could be adjusted to 5, 15, or 20 mg in accordance with clinical
      criteria (efficacy, tolerance). Eighty-eight percent of the patients were
      maintained on 10 mg of bisoprolol. The frequency of angina attacks was reduced in
      89% of all patients: 56% became free of angina attacks. There were no differences
      in response as related to age and smoking habits. Bisoprolol was well tolerated.
      Beta-blocker-specific side effects were observed in 12 patients (5.1%). In
      conclusion, bisoprolol administered once daily appears to be an effective and
      safe antianginal agent.

PMID- 11527132
TI  - Beta-adrenoceptor-blocking drugs in the elderly.
AB  - Beta-adrenoceptor function appears to be diminished in the elderly, although the
      exact mechanisms are still uncertain. Some evidence suggests that this
      attenuation is predominantly of beta1-receptor activity, with beta2-receptor
      activity remaining intact. Pharmacokinetic changes also occur in the elderly with
      beta-blockers. Absorption is unchanged but bioavailability may be increased,
      particularly with lipophilic drugs such as propranolol that are subject to "first
      pass" effects. Both hepatic and renal clearance may be diminished, and this
      suggests that, in general, elderly patients will require smaller doses than those
      normally given to younger ones. Although antihypertensive response to beta
      blockers has been linked to renin status, clinical trial evidence indicates that
      beta-blockers are effective antihypertensive agents in the elderly, and clinical
      experience suggests that this is true also for ischemic heart disease. Provided
      attention is given to patient selection, associated diseases, and dosage, in
      general, beta-blockers appear to be well tolerated in the elderly. However,
      careful clinical supervision is required, particularly during treatment
      initiation.

PMID- 11527133
TI  - Antiarrhythmic properties of beta-blockers.
AB  - Beta-blockers are effective antiarryhthmic agents for certain types of
      supraventricular and ventricular arrhythmias. They are able to prevent
      arrhythmias associated with sympathetic hyperactivity, suppress automaticity, and
      slow conduction in myocardial tissue with predominant slow-response activity. In
      animal experiments, beta-blockers have been shown to exert pronounced
      antifibrillatory effects following occlusion of a main coronary artery. This
      effectiveness may be the basis for the improved survival of patients with chronic
      coronary artery disease under long-term beta-blockade. Side effects are often
      dose-related; the optimal and minimal effective doses of the beta-blocker are
      critical in limiting adverse effects. As conventional antiarrhythmic agents have
      not been shown to reduce the risk of mortality in postmyocardial infarction
      patients, a broader application of beta-blockers as antiarrhythmic agents within
      the future, possibly in combination with class I or III drugs, seems conceivable.

PMID- 11527134
TI  - Beta-blockade and brachial artery hemodynamics in hypertension.
AB  - The effect of systemic adrenergic blockade on hypertensive brachial arteries was
      studied in humans with pulsed Doppler flowmetry. Blockade of beta-receptors by
      the nonselective beta-blocking agent propranolol did not modify the brachial
      artery diameter, whereas pindolol increased this parameter for the same degree of
      blood pressure reduction. The beta1-selective blocking agents atenolol and
      bisoprolol caused similar decreases in blood pressure and a reduction in the
      diameters of the brachial artery and abdominal aorta, respectively. The
      combination of alpha- and beta-blockade produced a rapid drop in blood pressure
      but did not change the brachial arterial diameter. Thus, following beta-blockade,
      the arterial diameter increased, did not change, or even decreased despite an
      adequate blood pressure reduction. It is suggested that beta-blockade in some
      instances resets the pressure-diameter curve and therefore has a direct action on
      the arterial wall independent of the mechanical effect of blood pressure
      reduction.

PMID- 11527135
TI  - Long-term treatment of angina pectoris with bisoprolol or atenolol in patients
      with chronic obstructive bronchitis: a randomized, double-blind crossover study.
AB  - Forty outpatients suffering from angina pectoris due to coronary artery disease
      and concomitant reversible. chronic obstructive bronchitis were treated with the
      beta1-selective beta-blockers atenolol (50 mg) and bisoprolol (5 mg) for 6 months
      in each case, following a randomized, double-blind crossover study design. Lung
      function tests were carried out by means of whole-body plethysmography before and
      then several times during treatment. 2 to 4 h after drug intake (once daily in
      the morning). The main target variables for the factorial analysis of variance
      for comparison of the two beta-blockers were the airway resistance (AWR), the
      forced expiratory volume in the first second (FEV1), and the peak expiratory flow
      rate (PEFR). Bicycle ergometry was performed before and after therapy in order to
      check the cardiovascular effects of the two beta-blockers. The patients were
      questioned as to their angina pectoris and bronchitis symptoms at the monthly
      check-ups. There was no difference between the two beta-blockers (p > 0.05), both
      causing a slight increase in AWR, which increased with therapy duration, and a
      small but significant decrease in FEV1 and PEFR (p < 0.01). The bronchitis
      symptoms were not affected; however, seasonal influences were detected. Atenolol
      and bisoprolol had comparably pronounced effects on the cardiovascular parameters
      during ergometry (blood pressure, heart rate, W x min product, and ST-segment
      depression) and the frequency of angina pectoris attacks. Even beta1-selective
      beta-blockers may cause an impairment of lung function in patients with chronic
      obstructive bronchitis. This may be due to the presence of beta1-adrenoceptors in
      the bronchial tissue. Fifty milligrams of atenolol and 5 mg of bisoprolol once
      per day are effective in the treatment of angina pectoris.

PMID- 11527136
TI  - Beta-receptor blockade, physical activity, and metabolism.
AB  - The adaptation processes under physical activity are regulated through an
      increase in the sympathetic impulse, whereby the circulation adaptation is
      mediated specifically by way of beta1-receptors and the energy supply
      predominantly by way of beta2-receptors. The maximum performance capacity,
      therefore, is restricted through every form of beta-blockade. However, it follows
      from the receptor pattern that the mixed beta1/beta2-blockade exhibits a
      substantially clearer effect. For everyday performance, the predominant beta1
      selective blockade represents practically no handicap. The special advantages of
      beta1-selective-compared to nonselective-blockade are discussed. Beta1-blockers
      practically do not affect glycogenolysis. Under beta1/beta2-blockers,
      hypoglycemia could reactively lead to reflective pressure increases and
      bradycardia through epinephrine release. Beta1-blockers additionally influence
      the cellular potassium homeostasis to a substantially lower extent. Under
      nonselective blockers, a distinct increase in the serum potassium and a
      retardation of the reuptake in the cells are observed. Also, lipolysis is
      strongly negatively influenced under nonselective blockers. Especially for
      atherogenesis, the important high-density lipoprotein cholesterol is negatively
      influenced under nonselective blockers in contrast to selective ones. Under these
      aspects, results are demonstrated that were obtained in 16 hypertensive patients
      treated with bisoprolol. In conclusion, beta1-selective blockers are largely
      "metabolically neutral" and are therefore to be preferred.

PMID- 11527137
TI  - Influence of multiple risk factors on the hazard of hypertension.
AB  - Atherosclerosis and coronary artery disease (CAD) are now the commonest sequelae
      of hypertension and all clinical manifestations of CAD occur in excess in persons
      with elevated blood pressure. Risk increases in relation to the extent of blood
      pressure elevation whether this is in the systolic or diastolic component, at any
      age and in either sex. Even isolated systolic hypertension increases
      cardiovascular risk. Elevated pressures are often accompanied by lipid
      abnormalities, hyperglycemia, elevated fibrinogen, obesity, and ECG
      abnormalities, all of which augment the risk. These risk factors associated with
      hypertension influence the coronary risk potential more than the nature of the
      blood pressure elevation. Although blood pressure makes an independent
      contribution to CAD, the risk at any level of pressure is markedly influenced by
      the cardiovascular risk profile. In mild to moderate hypertension in particular,
      the risk of CHD is concentrated in those who have impaired glucose tolerance,
      increased total/HDL ratio, ECG abnormalities, and smoke cigarettes. One or more
      of these associated risk factors also predisposes to other cardiovascular
      sequelae of hypertension, including stroke, peripheral vascular disease, and
      cardiac failure. The presence of organ involvement indicated by proteinuria,
      evidence of impaired ventricular function, or left ventricular hypertrophy
      greatly escalates the risk and usually indicates a compromised coronary
      circulation. Most myocardial infarctions and sudden deaths occur prior to the
      appearance of such evidence. Hypertensive risk assessment requires consideration
      of the multivariate risk profile because of the interdependence of the risk
      factors. The nature and urgency of treatment is better determined from such a
      risk profile than from the blood pressure parameters alone. Optimal preventive
      management of hypertension requires more than normalization of the blood pressure
      if coronary sequelae are to be avoided.

PMID- 11527138
TI  - Beta-blockers vs. thiazides in the treatment of hypertension: a review of the
      experience of the large national trials.
AB  - The effects of antihypertensive treatment on cerebrovascular disease and coronary
      artery disease (CAD) end points reported in the large-scale national trials have
      differed. All trials have shown stroke benefit, whereas CAD benefit has not been
      convincingly demonstrated in any. In three trials, the effects of thiazide- and
      beta-blocker-based regimens can be directly compared. In the MRC Treatment Trial
      for Mild Hypertension in Britain, the largest of the trials and the only one to
      compare these two classes of drugs with each other and with untreated controls,
      stroke benefit was significantly greater in the thiazide than in the beta-blocker
      group (p = 0.002). Indeed, the 70% reduction in fatal strokes and 65% reduction
      in nonfatal strokes suggested an effect on cerebral infarction as well as on
      cerebral hemorrhage. Opposing trends were found for CAD end points with beta
      blockers and thiazides when compared with controls. For coronary events, sudden
      deaths, and ECG changes of infarction, significant differences were found between
      the reduced rates for those receiving propranolol and the higher rates for those
      receiving bendrofluazide. Weak evidence has been put forward by four trials
      MRFIT, HDFP, the Oslo trial, and the MRC trial-suggesting that thiazide treatment
      for those who already have evidence of coronary disease may be harmful. In no
      case is the evidence conclusive, and it involves only a small (but important)
      subgroup. In the MRC trial, a nonselective beta-blocker, propranolol, provided
      greater CAD benefit as measured by the incidence of myocardial infarction, sudden
      death, and ECG changes, but only in nonsmokers. Hypotheses generated by these
      trials need further investigation.

PMID- 11527139
TI  - Primary prevention with beta-blockade in patients with hypertension: review of
      results and clinical implications.
AB  - The MAPHY primary prevention study in hypertensive men aged 40-64 years with
      diastolic blood pressure above 100 mm Hg showed that total mortality, sudden
      cardiovascular death, and the pooled incidence of fatal and definite nonfatal
      coronary events were significantly lower in patients randomized to metoprolol (n
      = 1,609) than in patients randomized to diuretics (n = 1,625) (p = 0.028, p =
      0.017, and p = 0.001, respectively). The publication of the mortality results
      aroused great interest as well as a number of comments in the literature. The aim
      of this review is to present comments on the study design, results, and clinical
      implications of primary preventive studies performed with beta-blockers in
      hypertension. Statistical analyses of the MAPHY study results convincingly show a
      substantially lower risk for coronary events in patients on metoprololin relative
      terms, about a 25% reduction compared with diuretics-with beneficial preventive
      effects on coronary events both in smokers and nonsmokers. Supporting evidence
      for the MAPHY study results are available from several other clinical studies in
      hypertensive men and also from experimental, clinical, and animal studies. The
      results indicate that the difference in mortality and coronary events in the
      studies performed probably is mediated via mechanisms other than blood pressure
      control. Benefits have been attributed to the beta1-blockade of treatment, and
      evidence suggests that relatively lipophilic beta-blockers are best documented.
      Cardioselectivity appears to be an advantage for the risk reduction in smokers
      and also concerning side effects and quality of life. Thus, available data
      support the choice of a beta-blocker as antihypertensive therapy in patients with
      increased risk for coronary events unless contraindications limit the choice of
      these agents. Furthermore, primary prevention and risk reduction in hypertensives
      is dependent not only on the choice of the antihypertensive agent but also on
      improved detection and management of the other cardiovascular risk factors.

PMID- 11527140
TI  - Beta-blocker effects on plasma lipids in antihypertensive therapy: importance of
      the duration of treatment and the lipid status before treatment.
AB  - The aim of this study was to evaluate the effects of long-term monotherapy with
      four beta-blockers provided with different pharmacological properties on plasma
      lipids in both normocholesterolemic and hypercholesterolemic hypertensive
      patients. After a 1-month run-in period on placebo, 70 hypertensive patients with
      basal total cholesterol (TC) < or = 220 mg/dl were treated for 3 years with
      propranolol 160 mg/day or atenolol 100 mg/day or bisoprolol 10 mg/day or
      mepindolol 10 mg/day, while 59 hypertensive patients with basal TC > 220 mg/dl
      were given the same beta-blockers at the same dosage for 6 months. In both
      normocholesterolemic and hypercholesterolemic hypertensive patients. HDL-C and
      triglyceride (TG) levels showed significant changes that appeared to be related
      to the type of beta-blocker used and to the duration of therapy. Nonselective,
      non-ISA (intrinsic sympathomimetic activity) propranolol caused the most
      pronounced changes, decreasing HDL-C and increasing TG concentrations; beta1
      selective atenolol and bisoprolol had similar, but less remarkable effects; even
      more discrete changes were observed on mepindolol (with ISA). The variations in
      HDL-C and TG values reached their peak in 6-12 months of beta-blocker therapy;
      then, after a plateau phase, they showed a progressive trend toward pretreatment
      levels. In hypercholesterolemic patients, the percent change in both HDL-C and TG
      values was lower compared to normocholesterolemic patients.

PMID- 11527141
TI  - Comparison of beta-blockade and ACE inhibitors in the treatment of hypertension.
AB  - There are important pharmacodynamic differences between the various beta
      adrenoceptor-blocking drugs, whereas the angiotensin-converting enzyme (ACE)
      inhibitors differ mainly in their pharmacokinetic properties. The differing
      properties of the beta-blocking drugs may contribute to their antihypertensive
      effect; possibly, the beta1-selective agents are slightly more effective.
      Comparisons between groups of drugs may not be fully applicable to all members of
      the group. Overall, however, beta-blocking drugs and ACE inhibitors appear to
      control the resting blood pressure to a similar degree, whereas on exercise the
      rise in blood pressure is inhibited to a greater extent by beta1-blockade. ACE
      inhibitors reverse the hemodynamic changes of hypertension in contrast to beta1
      blocking drugs without intrinsic sympathomimetic activity (ISA). Neither group of
      drugs interferes with cardiovascular reflexes such as the response to posture.
      The beta-blocking drugs have specific contraindications such as asthma and heart
      failure. Although some earlier studies suggested otherwise, more recent smaller
      investigations suggest that overall patient acceptability of ACE inhibitors and
      beta-blockers is similar. In certain instances, particularly in the presence of
      diuretics, a large first-dose effect with a profound fall in blood pressure may
      be seen with ACE inhibitors. In contrast to other drugs, there is some evidence
      that beta-blocking drugs have a cardioprotective effect. ACE inhibitors and beta
      blocking drugs have a similar spectrum of activity, with black patients
      responding less well. Although in dispute, drugs are often useful in the elderly.
      Both groups possess additional therapeutic indications that may influence the
      choice to treat hypertension.

PMID- 11527142
TI  - Circadian pattern of blood pressure and heart rate in the longer term after heart
      transplantation.
AB  - A loss of the circadian rhythm pattern of the blood pressure (BP) and heart rate
      (HR) as well as the development of hypertension has been found after heart
      transplantation (Htx). To determine whether a reappearance of this rhythm occurs
      in the long term after Htx, we used 24-h ambulatory monitoring to study 27
      patients 1.7+/-1.6 years (range of 10 days to 4.3 years) after Htx. Patients were
      divided into two groups: group I (short term), Htx less than 6 months (n = 7);
      and group 2 (long term), Htx more than 6 months previously (n = 20). Group 2 had
      significantly higher diastolic BP as well as a greater fall in systolic BP during
      the night (-0.4+/-8.0 vs. 9.0+/-7.2 mm Hg, p < 0.01). There was also a higher day
      HR found in group 2 (73.2+/-14.5 vs. 96.8+/-12.5 beats/min, p < 0.001) as well as
      a larger fall in night HR in group 2 (4.2+/-5.5 vs. 11.9+/-4.9 beats/min, p <
      0.005). The return of the circadian rhythm pattern in the longer term after Htx
      may result from partial reinervation of the heart, although other neurohumoral
      factors or concomitant medication (lower steroid dosages) may play a role.

PMID- 11527143
TI  - Prevention of stress-induced hypertension in hypertensive patients.
AB  - The aim of the study was to assess the course of the alerting reaction during an
      effective antihypertensive treatment, and to discuss its interference with the
      conduct of therapy. In 28 patients suffering from mild to moderate hypertension,
      the basal blood pressure was measured in an outpatient clinic according to a
      standardized procedure, first by a nurse, then by a 12-min recorded monitoring,
      and then by a physician using a mercury sphygmomanometer with the patient in the
      upright and then the supine position. In comparison with the monitoring (mean
      values recorded at 6, 9, and 12 min), there was a significant increase in
      diastolic and systolic blood pressure taken by the nurse and by the physician,
      which diminished at the end of the visit with the physician. Patients then
      received 10 mg of bisoprolol each morning and presented again on day 30 and day
      60, following the same procedure and under identical conditions. Despite the
      desired antihypertensive effect, the alerting reaction persisted at each visit up
      to the end of the study, being unchanged in the case of the systolic blood
      pressure and accentuated in the case of the diastolic blood pressure. Our results
      confirm those of previous investigations showing that even an effective
      antihypertensive therapy is unequivocally associated with a persisting alerting
      reaction irrespective of the antihypertensive drug applied. Thus, patients may be
      exposed to the potential risk involved with false failures and unnecessary
      overtreatment. The physician must compare his or her own measurements with
      readings made outside the consulting office and must program ambulatory blood
      pressure monitoring in the case of discrepancy. This is a suitable means of
      confirming and validating blood pressure measurements, as this method does not
      record the alerting reaction.

PMID- 11527144
TI  - Bisoprolol and nifedipine SR in the treatment of hypertension in the elderly.
AB  - Forty outpatients (11 men and 29 women) aged between 65 and 85 years (mean age of
      68 years) with mild to moderate hypertension [mean systolic/diastolic blood
      pressure (SBP/DBP) after 2 weeks on placebo of 175/102 mm Hg] were included in a
      randomized, double-blind, parallel-group study to compare the efficacy and
      tolerance of 10 mg of bisoprolol once daily (o.d., n = 20) and 20 mg of
      nifedipine sustained release (SR) b.i.d. (n = 20) during 4 weeks of treatment.
      SBP and DBP were significantly reduced compared to baseline with both treatments.
      There was no significant difference in efficacy between the two treatments after
      2 and 4 weeks. After 2 weeks, the number of patients with normalized DBP (< or
      =90 mm Hg) was higher with bisoprolol than with nifedipine, this difference no
      longer being present after 4 weeks. Resting heart rate was significantly reduced
      with bisoprolol from 78+/-8 to 68+/-9 beats/min after 4 weeks, but there was no
      change in heart rate with nifedipine. Adverse events were reported by 6 patients
      on bisoprolol (20 events) and 12 patients on nifedipine (51 events) and the
      overall tolerance of bisoprolol was considered to be significantly better than
      that of nifedipine. Because bisoprolol is equally effective when administered
      once daily in comparison with nifedipine SR, which has to be given twice daily,
      and since bisoprolol exhibits a better tolerance, this beta-blocker appears to be
      a useful drug of first choice for the treatment of elderly hypertensive patients.

PMID- 11527145
TI  - Human BMP-7/OP-1 induces the growth and differentiation of adipocytes and
      osteoblasts in bone marrow stromal cell cultures.
AB  - We studied the effects of BMP-7/OP-1 on growth and differentiation of bone marrow
      stromal cells. BMS2, a mouse bone marrow stromal cell line capable of
      differentiating into adipocytes and osteoblasts, were treated in a serum-free
      medium containing differentiation agents that favor the expression of both
      lineages. BMP-7/OP-1 stimulated cell proliferation and differentiation
      concomitantly. These effects were dose- and growth phase-dependent. Cells were
      more sensitive to the treatment early in the culture (30-40% confluence) with a
      significant increase in cell proliferation and markers of differentiation at low
      concentrations. When treated later in the growth phase (90-100% confluence), no
      significant increase in cell proliferation was seen. The concentration
      requirement for cells later in the culture to reach an equivalent degree of
      differentiation was 3-10- fold higher than for cells treated early. In both
      cases, the effects on adipocyte differentiation were biphasic; low concentrations
      stimulated adipocyte differentiation which was inhibited at higher concentrations
      where stimulation of osteoblast markers were observed. We conclude that cell
      proliferation and cell differentiation into adipocyte/osteoblast can occur
      simultaneously under BMP-7/OP-1 treatment.

PMID- 11527147
TI  - Membrane-Bound and cytosolic forms of heterotrimeric G proteins in young and
      adult rat myocardium: influence of neonatal hypo- and hyperthyroidism.
AB  - Membrane and cytosolic fractions prepared from ventricular myocardium of young
      (21-day-old) hypo- or hyperthyroid rats and adult (84-day-old) previously hypo-
      or hyperthyroid rats were analyzed by immunoblotting with specific anti-G-protein
      antibodies for the relative content of Gs alpha, Gi alpha/Go alpha, Gq alpha/G11
      alpha, and G beta. All tested G protein subunits were present not only in
      myocardial membranes but were at least partially distributed in the cytosol,
      except for Go alpha2, and G11 alpha. Cytosolic forms of the individual G proteins
      represented about 5-60% of total cellular amounts of these proteins. The long (Gs
      alpha-L) isoform of Gs alpha prevailed over the short (Gs alpha-S) isoform in
      both crude myocardial membranes and cytosol. The Gs alpha-L/Gs alpha-S ratio in
      membranes as well as in cytosol increased during maturation due to a substantial
      increase in Gs alpha-L. Interestingly, whereas the amount of membrane-bound Gi
      alpha/Go alpha and Gq alpha/G11 alpha proteins tend to lower during postnatal
      development, cytosolic forms of these G proteins mostly rise. Neonatal
      hypothyroidism reduced the amount of myocardial Gs alpha and increased that of Gi
      alpha/Go alpha proteins. By contrast, neonatal hyperthyroidism increased
      expression of Gs alpha and decreased that of Gi alpha and G11 alpha in young
      myocardium. Changes in G protein content induced by neonatal hypo- and
      hyperthyroidism in young rat myocardium were restored in adulthood. Alterations
      in the membrane-cytosol balance of G protein subunits associated with maturation
      or induced by altered thyroid status indicate physiological importance of
      cytosolic forms of these proteins in the rat myocardium.

PMID- 11527146
TI  - Cepharanthine activates caspases and induces apoptosis in Jurkat and K562 human
      leukemia cell lines.
AB  - Cepharanthine (CEP) is a known membrane stabilizer that has been widely used in
      Japan for the treatment of several disorders such as anticancer therapy-provoked
      leukopenia. We here report that apoptosis was induced by low concentrations (1-5
      microM) of CEP in a human leukemia T cell line, Jurkat, and by slightly higher
      concentrations (5-10 microM) in a human chronic myelogenous leukemia (CML) cell
      line K562, which expresses a p210 antiapoptotic Bcr-Abl fusion protein. Induction
      of apoptosis was confirmed in both Jurkat and K562 cells by DNA fragmentation and
      typical apoptotic nuclear change, which were preceded by disruption of
      mitochondrial membrane potential and were induced through a Fas-independent
      pathway. CEP treatment induced activation of caspase-9 and -3 accompanied by
      cleavage of PARP, Bid, lamin B1, and DFF45/ICAD in both Jurkat and K562 cells,
      whereas caspase-8 activation and Akt cleavage were observed only in Jurkat cells.
      The CEP-induced apoptosis was completely blocked by zVAD-fmk, a broad caspase
      inhibitor. Interestingly, CEP treatment induced remarkable degradation of the Bcr
      Abl protein in K562 cells, and this degradation was prevented partially by zVAD
      fmk. When used in combination with a nontoxic concentration of herbimycin A,
      lower concentrations (2-5 microM) of CEP induced obvious apoptosis in K562 cells
      with rapid degradation or decrease in the amount of Bcr-Abl and Akt proteins. Our
      results suggest that CEP, which does not have bone marrow toxicity, may possess
      therapeutic potential against human leukemias, including CML, which is resistant
      to anticancer drugs and radiotherapy.

PMID- 11527148
TI  - Transcriptional state and chromatin structure of the murine entactin and laminin
      gamma1 genes.
AB  - The positions of nucleosomes in the proximal 5' regions of the coordinately
      regulated murine entactin/nidogen and laminin gamma1 genes have been identified
      in four different transcriptional states--constitutively off, basal, induced, and
      constitutively induced. In the entactin gene a 450 base pair (bp) region of open
      chromatin is present between three positioned nucleosomes and the transcriptional
      start site in the basal, induced, and constitutively induced states. Additionally
      there is a 200 bp open chromatin region at approximately -2.1 kbp that is only
      present in the induced and constitutively induced states. In the laminin gamma1
      gene, a 650 bp region of nucleosome-free chromatin is present between nucleosomes
      positioned at approximately -750 and +120 in all transcriptionally active states.
      These results suggest that basal co-expression of these genes requires sites
      present in these near upstream regions. The induction to high levels appears to
      involve additional sites and possibly the production of new and/or the
      modification of existing trans-acting factors.

PMID- 11527149
TI  - Properties of exogenously added GPI-anchored proteins following their
      incorporation into cells.
AB  - Isolated glycosylphosphatidylinositol (GPI)-anchored proteins, when added to
      cells in vitro, incorporate into their surface membranes and, once incorporated,
      exert their native functions. Virtually any protein of interest, if expressed as
      a GPI-reanchored derivative, can be modified to acquire this capacity. Such
      transfer of proteins directly to cells, termed "protein engineering" or
      "painting" constitutes an alternative to conventional gene transfer for
      manipulating cell surface composition that has many potential applications.
      Previous studies with incorporated GPI-anchored proteins have focused almost
      entirely on their extracellular functions. In this study, biotinylated human
      erythrocyte (E(hu)) decay accelerating factor, E(hu) acetylcholinesterase, and
      GPI-reanchored murine B7-1 and B7-2 were used as GPI-anchored reporters to
      characterize their plasma membrane organization and cell signalling properties
      following addition to Hela or Chinese hamster ovary cells. For each reporter,
      three types of cell-association were documented; (1) nonphysiological attachment
      and/or incomplete insertion, (2) uncomplexed membrane integration, and (3)
      organization into TX-100-resistant microdomains. Transit from the first two
      compartments into the third, i.e., microdomains, progressed slowly, continuing
      even after 24 to 36 h and was associated with the acquisition of cell signalling
      capacity. All four reporters, incorporated in two different detergents, behaved
      similarly. When organized in microdomains, caveolin and other GPI proteins co
      isolated with the incorporated reporter. These results have implications for
      protein engineering of cells in general, and in particular, for cells such as
      modified tumor cell immunogens administered to patients for therapeutic purposes.

PMID- 11527150
TI  - Cloning and characterization of human syndecan-3.
AB  - Syndecans are cell-surface heparan sulfate proteoglycans, which perform a variety
      of functions in the cell. Most important, they are co-receptors for growth
      factors and mediate cell-cell and cell-matrix interactions. Four syndecans
      (syndecan 1-4) have been described in different species. The aim of this work was
      the cloning and characterization of human syndecan-3. The human syndecan-3
      sequence has high homology to the rat and mouse sequences, with the exception of
      the 5'-region. Syndecan-3 mRNA is mostly expressed in the nervous system, the
      adrenal gland, and the spleen. When different cell lines were transiently
      transfected with full-length syndecan-3 cDNA, it was localized to the membrane
      and induced the formation of long filopodia-like structures, microspikes, and
      varicosities. Consequently, the actin cytoskeleton was re-organized, since actin
      staining was mostly found in the cellular extensions and at the cell periphery,
      co-localizing with the syndecan-3 staining. The development of the phenotype
      depended on the presence of sugar chains, as transfected glycosaminoglycan
      deficient Chinese hamster ovary (CHO) 745 cells did not show these structural
      changes, nor did transfected CHO K1 cells in the presence of heparin. The
      similarity of the cloned DNA sequence with that of other mammalian species and
      the high expression in the nervous system led us to the assumption that human
      syndecan-3 could perform comparable functions to those described for syndecan-3
      in rat and mouse. Additionally, transient transfection experiments suggest a role
      of human syndecan-3 in the organization of cell shape by affecting the actin
      cytoskeleton, possibly by transferring signals from the cell surface in a sugar
      dependent mechanism.

PMID- 11527151
TI  - Inducible expression of the alpha2-macroglobulin signaling receptor in response
      to antigenic stimulation: a study of second messenger generation.
AB  - Thioglycollate (TG)-elicited murine, peritoneal macrophages express two receptors
      for activated forms of the proteinase inhibitor alpha2-macroglobulin (alpha2M*)-
      namely, the low density lipoprotein receptor-related protein (LRP) and the
      alpha2M signaling receptor (alpha2MSR). We now report that resident peritoneal
      macrophages express only 400+/-50 alpha2MSR receptors/cell compared to 5000+/-500
      receptor/TG-elicited macrophage. By contrast, LRP expression is only 2-2.5-fold
      greater on elicited cells. The low level of alpha2MSR expression by resident
      cells is insufficient to trigger signal transduction in contrast to TG-elicited
      cells which when exposed to alpha2M* demonstrate a rapid rise in inositol 1,4,5
      trisphosphate and a concomitant increase in cytosolic free Ca2+. We then studied
      a variety of preparations injected subcutaneously for their ability to upregulate
      alpha2MSR. Macroaggregated bovine serum albumin (macroBSA) injection upregulated
      alpha2MSR and triggered signaling responses by splenic macrophages. Nonaggregated
      BSA injection alone or in the presence of alum, by contrast, did not alter
      alpha2MSR expression. Recombivax (hepatitis B antigen adsorbed to alum) injection
      also upregulated alpha2MSR on splenic macrophages while the alum carrier had no
      effect. We conclude that macrophage alpha2M* receptors are inducible and their
      expression may be regulated, in part, by potential antigens.

PMID- 11527152
TI  - Nitroxide TEMPOL impairs mitochondrial function and induces apoptosis in HL60
      cells.
AB  - The piperidine nitroxide TEMPOL induces apoptosis in a number of tumor cell lines
      through free radical-dependent mechanisms. As mitochondria play a major role in
      apoptosis as both source and target for free radicals, the present study focuses
      on mitochondrial effects of TEMPOL in a human promyelocytic leukemic cell line
      (HL-60). On 24-h exposure to TEMPOL, the following alterations were observed: 1)
      decrease in both the intracellular and mitochondrial glutathione pools; 2)
      impairment of oxidative phosphorylation; and 3) decrease in mitochondrial
      membrane potential. In addition, TEMPOL was found to specifically target complex
      I of the respiratory chain, with minor effects on complexes II and IV, suggesting
      that mitochondrial effects might play a role in TEMPOL-induced oxidative stress
      and apoptosis, and that TEMPOL might sensitize tumor cells to the pro-apoptotic
      effects of cytotoxic agents.

PMID- 11527153
TI  - Recombinant Semliki Forest virus enhanced plasminogen activator inhibitor 1
      expression and storage in the megakaryocytic cell line MEG-01.
AB  - Platelet plasminogen activator inhibitor I (PAI-1), a trace alpha-granule
      protein, is a key physiological regulator of fibrinolysis. Because information on
      the packaging of PAI-1 into alpha-granules during megakaryocytopoiesis may reveal
      novel approaches for controlling hemostasis, this study investigated basal,
      plasmid-mediated, and alphavirus-mediated PAI-1 packaging into alpha-granules
      like structures in the megakaryocytic cell line MEG-01. Differentiation of MEG-01
      cells with phorbol myristate acetate (PMA) was observed to result in a four-fold
      increase in both secreted and cell-associated PAI-1 antigen over a four day
      period. Subcellular fractionation of PMA-treated MEG-01 cells on 45% self-forming
      Percoll gradients was employed to separate low density membrane and Golgi-rich
      fractions from a high density granule-containing region. A subsequent 30-60% pre
      formed Percoll gradient was employed to remove contaminating lysosomes from the
      PAI-1/glycoprotein IIbIIIa-containing granules. Electron microscopy showed that
      these MEG-01 granules share a similar size distribution (350-600 nm) and
      morphology to platelet alpha-granules. PAI-1 (40 ng/mg protein) in isolated MEG
      01 storage granules was approximately 10% of the levels present in isolated
      platelet alpha-granules. To elevate PAI-1 production/storage, two expression
      systems were investigated. Experiments with plasmids encoding PAI-1 and beta
      galactosidase resulted in low transfection efficiency (0.001%). In contrast,
      Semliki Forest virus (SFV)-mediated gene transfer increased cellular PAI-1 by 31
      fold (1,200 ng/10(6) cells at 10 MOI) in comparison to mock-infected cells. Pulse
      chase experiments demonstrated that SFV/PAI-1 mediated gene expression could
      enhance PAI-1 storage 6-9-fold, reaching levels present within platelets. To
      document the ability of PAI-1 to be stored in a rapidly releasable form in MEG-01
      cells, we isolated platelet-like particles from the media conditioned by the
      cells and examined secretagogue-induced release of PAI-1. Particles from SFV/PAI
      1 infected cells display a 5-fold enhanced secretion of PAI-1 following treatment
      with ADP in comparison to particles incubated in the absence of secretagogue.
      These results suggest that SFV mediated gene expression in MEG-01 cells provides
      a useful framework for analyzing the production and storage of alpha-granule
      proteins.

PMID- 11527154
TI  - IL-1beta sensitizes intervertebral disc annulus cells to fluid-induced shear
      stress.
AB  - Chronic inflammation and altered mechanical loading are implicated as
      contributors to intervertebral disc degeneration. Biomechanical and biochemical
      factors play a role in disc degeneration but have received limited study.
      Mechanically, intervertebral discs are sheared during bending or twisting of the
      trunk. Biochemically, IL-1beta, detected in degenerative discs, promotes
      metalloproteinase expression. We hypothesized that disc cells might respond to
      shear stress and IL-1beta in a calcium signaling response. We measured the effect
      of single and combined stimuli on intracellular calcium concentration ([Ca2+]ic)
      and signaling. Cells were isolated from annulus tissue, cultured to quiescence,
      plated on collagen-bonded Culture Slips and incubated with Fura-2AM. Cells then
      were incubated in IL-1beta. Cell response to the effects of fluid flow was tested
      using FlexFlo, a laminar flow device. Human annulus (hAN) cells responded to
      laminar fluid flow with a one to three-fold increase in [Ca2+]ic. IL-1beta alone
      produced a small, transient stimulation. hAN cells pretreated with IL-1beta
      responded to shear with a more dramatic and sustained increase in [Ca2+]ic, six
      to ten-fold over basal level, when compared to shear then IL-1beta or shear and
      IL-1beta alone (P<0.001 for all comparisons). This is the first study documenting
      synergism of a signaling response to biomechanical and biochemical stimuli in
      human disc cells. IL-1beta treatment appeared to "sensitize" annulus cells to
      mechanical load. This increased responsiveness to mechanical load in the face of
      inflammatory cytokines may imply that the sensitivity of annulus cells to shear
      increases during inflammation and may affect initiation and progression of disc
      degeneration.

PMID- 11527155
TI  - Breakpoints of t(4;11) translocations in the human MLL and AF4 genes in ALL
      patients are preferentially clustered outside of high-affinity matrix attachment
      regions.
AB  - Chromosomal translocations t(4;11) are based on illegitimate recombinations
      between the human MLL and AF4 genes, and are associated with high-risk acute
      leukemias of infants and young children. Here, the question was asked, whether a
      correlation exists between the location of translocation breakpoints within both
      genes and the location of S/MARs. In "halo mapping experiments" (to define SARs),
      about 20 kb of MLL DNA was found to be attached to the nuclear matrix. Similar
      experiments performed for the translocation partner gene AF4 revealed that SARs
      are spanning nearly the complete breakpoint cluster region of the AF4 gene. By
      using short DNA fragments in "scaffold reassociation experiments" (to define
      MARs), similar results were obtained for both genes. However, Distamycin A
      competition experiments in combination with "scaffold reassociation experiments"
      revealed specific differences in the affinity of each tested DNA fragment to bind
      the isolated nuclear matrix proteins. When the latter data were compared with the
      known location of chromosomal breakpoints for both genes, an unexpected
      correlation was observed. DNA areas with strong MAR affinity contained fewer
      translocation breakpoints, while areas with weak or absent MAR affinity showed a
      higher density of chromosomal breakpoints.

PMID- 11527156
TI  - Genetic lesions and perturbation of chromatin architecture: a road to cell
      transformation.
AB  - Differential gene expression is a rigorously precise procedure that defines the
      developmental program of cells, tissues, organs, and of the entire organism. The
      correct execution of this program requires the participation of multiple and
      complex groups of regulators. In addition to transcription factors, which are key
      tools in ontogenesis by providing sequential switch of different genes, the
      structure of the chromatin is a dominant determinant leading to gene expression.
      Through the novel and insightful work of several investigators, it appears that
      the architecture of the chromatin spanning the genes can and does influence the
      efficiency of RNA transcription, and therefore of gene expression. Several new
      enzymatic complexes have been identified that reversibly modify the chromatin
      architecture by methylation, phosphorylation, and acetylation of the nucleosomal
      core proteins. These enzymes are crucial for the proper balance and maintenance
      of gene expression, and are often the target of mutations and alterations in
      human cancer. Here, we review briefly the current models proposing how some of
      these enzymes normally modify the chromatin structure and how their functional
      disruption leads to inappropriate gene expression and cell transformation.

PMID- 11527157
TI  - JNK phosphorylates the HSF1 transcriptional activation domain: role of JNK in the
      regulation of the heat shock response.
AB  - The role of c-Jun NH2-terminal kinase (JNK) signaling cascade in the stress
      inducible phosphorylation of heat shock factor 1 (HSF1) was investigated using
      known agonists and antagonists of JNK. We showed that treatment of HeLa cells
      with MG132, a proteasome inhibitor and known INK activator, caused the
      transcriptional activation domain of HSF1 to be targeted and phosphorylated by
      JNK2 in vivo. Dose-response and time course studies of the effects of heat shock
      and anisomycin treatment showed a close correlation of the activation of JNK and
      hyperphosphorylation of HSF1. SB203580 inhibited INK at the 100 microM
      concentration and significantly reduced the amount of hyperphosphorylated HSF1
      upon heat shock or anisomycin treatment. SB203580 and dominant-negative JNK
      suppress hsp70 promoter-driven reporter gene expression selectively at 45 degrees
      C but not at 42 degrees C heat stress, suggesting that JNK would be
      preferentially associated with the protective heat shock response against severe
      heat stress. The possibility that JNK-mediated phosphorylation of HSF1 may
      selectively stabilize the HSF1 protein and confers protection to cells under
      conditions of severe stress is discussed.

PMID- 11527159
TI  - Surgical therapy of parotid hemangiomas.
AB  - The goal of this review is to define the clinical characteristics of parotid
      hemangiomas in children and outline their therapeutic management. The records of
      42 pediatric patients with hemangiomas were reviewed; 10 required surgical
      treatment. Two cases of temporary postoperative facial nerve palsy were observed.
      Treatment was commonly delayed, and there is a significant likelihood of
      spontaneous regression. The indications for surgical intervention are an increase
      in tumor size, rapid tumor growth, failure of tumor size to decrease and
      hemorrhage into the lesion.

PMID- 11527160
TI  - Surgical closure of patent ductus arteriosus in very-low-birth-weight infants.
AB  - In many very-low-birth-weight (VLBW) infants the ductus arteriosus fails to close
      spontaneously, and they subsequently develop signs and symptoms of poor tissue
      perfusion and heart failure. This study evalutes the results of early surgical
      closure of patent ductus arteriosus (PDA). We retrospectively reviewed the
      records of all 101 VLBW infants who weighed 1,500 g or less when their PDA was
      surgically ligated in Turku University Hospital between 1988 and 1998. The mean
      gestational age at birth was 27.2 weeks and mean birth weight 963+/-239 g. The
      operation was performed at 12+/-8 days of age; the infants' weight at operation
      was 969+/-231 g and they were tracheally extubated 11+/-14 days after the
      operation. The surgery-related mortality was 3% (3/101) and overall mortality 10%
      (10/101). We conclude that surgical closure of PDA is safe and effective in VLBW
      infants.

PMID- 11527158
TI  - Differential sensitivity to apoptosis between the human small and large
      intestinal mucosae: linkage with segment-specific regulation of BCL-2 homologs
      and involvement of signaling pathways.
AB  - The small and large intestines differ in their expression profiles of Bcl-2
      homologs. Intestinal segment-specific Bcl-2 homolog expression profiles are
      acquired as early as by mid-gestation (18-20 weeks) in man. In the present study,
      we examined the question whether such distinctions underlie segment-specific
      control mechanisms of intestinal cell survival. Using mid-gestation human jejunum
      and colon organotypic cultures, we analyzed the impact of growth factors (namely
      insulin; 10 microg/ml) and pharmacological compounds that inhibit signal
      transduction molecules/pathways (namely tyrosine kinases, Fak, P13-K/Akt, and
      MEK/Erk) on cell survival and Bcl-2 homolog expression (anti-apoptotic: Bcl-2,
      Bcl-X(L), Mcl-1; pro-apoptotic: Bax, Bak, Bad). The relative activation levels of
      p125Fak, p42Erk-2, and p57Akt were analyzed as well. Herein, we report that (1)
      the inhibition of signal transduction molecules/pathways revealed striking
      differences in their impact on cell survival in the jejunum and colon (e.g., the
      inhibition of p125Fak induced apoptosis with a significantly greater extent in
      the jejunum [approximately 43%] than in the colon [approximately 24%]); (2) sharp
      distinctions between the two segments were noted in the modulatory effects of the
      various treatments on Bcl-2 homolog steady-state levels (e.g., inhibition of
      tyrosine kinase activities in the jejunum down-regulated all anti-apoptotics
      analyzed while increasing Bax, whereas the same treatment in the colon down
      regulated Bcl-X(L) only and increased all pro-apoptotics); and (3) in addition to
      their differential impact on cell survival and Bcl-2 homolog expression, the
      MEK/Erk and P13-K/Akt pathways were found to be distinctively regulated in the
      jejunum and colon mucosae (e.g., insulin in the jejunum increased p42Erk-2
      activation without affecting that of p57Akt, whereas the same treatment in the
      colon decreased p42Erk-2 activation while increasing that of p57Akt). Altogether,
      these data show that intestinal cell survival is characterized by segment
      specific susceptibilities to apoptosis, which are in turn linked with segmental
      distinctions in the involvement of signaling pathways and the regulation of Bcl-2
      homolog steady-state levels. Therefore, these indicate that cell survival is
      subject to segment-specific control mechanisms along the proximal-distal axis of
      the intestine.

PMID- 11527161
TI  - Cervical cystic hygroma: pre-, intra-, and post-operative morbidity and mortality
      in Zaria, Nigeria.
AB  - The management of extensive cystic hygromas in the cervical region (CCH) presents
      difficult challenges. A retrospective study of 41 children with CCH treated over
      24 years in Nigeria was carried out; there were 28 boys and 13 girls with an age
      range of 3 days to 10 years (median 6.5 months). Thirty-three (80%) presented
      with 34 life-threatening complications including infection in 11 (27%), rapid
      increase in cyst size in 10 (24%), respiratory obstruction in 7 (17%), and
      intracystic hemorrhage in 6 (15%). Complete excision was possible in only 14 of
      34 (41%) patients, and injuries to neighboring structures occurred in 6 (18%)
      (facial nerve 2, recurrent laryngeal nerve 1, internal jugular vein 1, parotid
      duct 1, pharynx 1). Postoperatively, 8 (24%) patients developed 9 complications.
      Wound infections occurred in 5 incompletely-excised cysts and 2 patients had
      respiratory obstruction. One patient with a wound infection developed edema of
      the tongue lasting several days and drainage was prolonged (> 6 weeks) in 1. Five
      patients died, 3 from respiratory obstruction and 1 each from wound and chest
      infection. Four patients (12%) developed a recurrence within 5 years of surgery.
      The pre-, intra-, and post-operative morbidity were high in this series. Although
      complete excision is the ideal treatment for CCH, this need not be pursued if
      neighboring structures are liable to injury. When cysts are incompletely excised,
      antibiotic prophylaxis is necessary as the incidence of wound infection is high.

PMID- 11527162
TI  - Funnel chest: treatment strategy and follow-up.
AB  - Although funnel chest is the most frequently seen deformity of the anterior chest
      wall in children, there is still considerable controversy regarding three major
      aspects, namely, the frequency of such deformities, their physiological
      importance, and the methods available for treatment. We retrospectively analyzed
      our experience with the 154 patients managed in our department. In 81 of these an
      operation was performed (OP), and the clinical findings for this group were
      compared with the 73 patients in whom an operation was not performed (NOP).
      Evaluation included subjective findings, especially the views of the patients'
      parents, and objective findings, including chest radiographs, computed tomography
      (CT), spirogram, electrocardiography, and echocardiography. In all patients the
      assessment included postoperative respiratory symptoms, appearance of the chest,
      and psychological aspects related to the deformity. Post-operatively, respiratory
      symptoms almost invariably subsided. The cosmetic result could initially be
      regarded as satisfactory or fair during the first 10 years following surgery, but
      over time there was frequently increasing concern regarding the scar. The NOP
      patients showed significantly less severity of the funnel index compared with OP
      patients. However, there was no spontaneous improvement in the deformity in older
      patients; most of the NOP patients continued to show a cosmetic deformity and
      26.7% had psychological problems. This retrospective study confirms that our
      treatment strategy of objective criteria for operation (functional compression
      index > 0.2, % vital capacity <80, and CT index less than 0.25) and timing of
      operation (between 4 and 6 years of age) provides good results. Based on the
      analysis of long-term follow-up, surgery is considered indicated in patients with
      severe deformity. However, in the interest of psychological development, the
      indications for surgery may be extended.

PMID- 11527163
TI  - Dumping syndrome: a common problem following Nissen fundoplication in young
      children.
AB  - Within a 3-year period we observed six children, aged 3 months to 4 years, with
      dumping syndrome (DS) following Nissen fundoplication. Five were neurologically
      normal and one was slightly mentally retarded. Symptoms included postprandial
      tachycardia, diaphoresis, lethargy, severe retching, meteorism or gas-bloat
      syndrome, watery diarrhea, refusal to eat with failure to thrive, and
      developmental delay. Results of an oral glucose tolerance test did not correlate
      with the severity of symptoms. In one child severe retching led to recurrent
      paraesophageal gastric herniation, necessitating two reoperations and a
      gastrostomy. A lack of meal stimulated pancreatic polypeptide release in this
      patient indicated vagal damage. Initially five of the six children needed
      continuous intragastric feeding until bolus application of a carbohydrate
      modified diet was tolerated. We conclude that the diagnosis of DS is often
      delayed in spite of characteristic clinical signs. Intensive postoperative follow
      up after antireflux surgery should be mandatory in children.

PMID- 11527164
TI  - Silo construction from a sterile adhesive film and polypropylene mesh in the
      repair of gastroschisis and omphalocele.
AB  - A simple technique of constructing a silo for the treatment of gastroschisis (GS)
      and omphalocele (OMP) is described. A polypropylene mesh covered on both sides
      with a sterile transparent adhesive film (incise drape) was used; both these
      items are freely available in the operating room. The resultant silo is sterile,
      soft, flexible, sturdy, internally smooth, provides a reasonable barrier, and
      allows enough visibility of the bowel. This silo was used in the treatment of 25
      cases of GS and 13 cases of OMP with acceptable results. Survival was better in
      patients in whom primary closure could be achieved in both OMP and GS. Silo
      treatment was associated with higher mortality from septic causes.

PMID- 11527165
TI  - The primary management of testicular maldescent in gastroschisis.
AB  - Gastroschisis (GS) is the commonest abdominal-wall defect in the Western world.
      The conventional practice has been reduction of the viscera and closure of the
      abdominal wall as an emergency procedure. The testis is often a part of the
      prolapsed viscera along with the bowel loops, stomach, fallopian tube, etc. The
      primary management of prolapsed (PT) (3) and intra-abdominal (5) testes (IAT) in
      this condition was studied in 16 consecutive male babies with GS, each was
      managed by simple reposition of the testes and closure of the abdominal wall. The
      babies were followed up for spontaneous descent of the testes. At 18-month follow
      up, all five IAT had descended into the scrotum spontaneously and were palpably
      normal. Of the three extra-abdominal PT, two had descended into the scrotum and
      were normal in size and on palpation. One was palpable in the superficial
      inguinal pouch. Simple reposition of the testes into the abdomen and closure of
      the abdominal defect is the correct approach for primary management of PT or IAT
      in a newborn with GS.

PMID- 11527166
TI  - Multiple gastrointestinal atresias result from disturbed morphogenesis.
AB  - Multiple gastrointestinal atresias (MGA) have been reported to account for 6% to
      32% of all intestinal atresias. Controversy exists regarding the pathogenesis.
      Many investigators believe MGA to be the result of multiple ischemic infarctions
      of the intestinal tract. However, some have suggested that MGA results from a
      malformative process early in fetal life. Prenatal exposure to adriamycin in a
      rat model has been reported to lead to a spectrum of tracheoesophageal and
      associated malformations of the gastrointestinal tract, including intestinal
      atresias, identical to these observed in humans. The aim of this study was to
      determine the incidence and histopathologic findings of MGA in order to
      understand the pathogenesis. Timed-pregnant Sprague-Dawley rats were injected
      with adriamycin (1.75 mg/kg) in nine different gestational-day protocols. MGA was
      only seen in those rats who received adriamycin on gestational days 7, 8, and 9.
      The litters were recovered on day 21 by cesarean section. The digestive tracts
      (DT) of the fetuses were harvested for macroscopic and microscopic examination.
      Ten rats who received adriamycin on gestational days 7, 8, and 9 produced 87
      newborns; 1 was damaged during dissection. DT anomalies occurred in 80 (93%) of
      the 86 newborns; 94% of these demonstrated MGA. There was a very high incidence
      of associated anomalies in newborns with MGA. Histologically, the blind-ending
      atresias showed different degrees of villous hyperplasia with or without
      intraluminal material. This is the first report demonstrating a high rate of
      occurrence of MGA in the adriamycin rat model. The injection of adriamycin early
      in gestation, the high incidence of associated malformations, and the anatomic
      and histologic findings in MGA indicate that MGA is a result of a malformative
      rather than an ischemic process.

PMID- 11527167
TI  - Splenic injuries in children: correlation between imaging and clinical
      management.
AB  - For non-operative management of splenic injuries in children, questions remain as
      regards imaging, length of hospital stay, and follow-up. We reviewed our
      experience concerning these issues over the past 15 years. The charts of all
      children with splenic injuries from January 1983 to December 1998 were reviewed.
      All computed tomography (CT) scans were reviewed and classified according to
      degree of splenic injury. Fisher's exact test and a linear regression model were
      used to analyze data. Sixty-nine males and 23 females under 16 years of age were
      identified; 57 (62%) had CT scans; 8 underwent a laparotomy; and 6 (6.5%) died.
      Age, on hemoglobin admission, and duration of intensive-care-unit stay were
      significantly related to hospital stay (median 8 days). Motor vehicle-pedestrian
      related injuries correlated significantly with mortality. CT class did not
      correlate with mortality (P = 0.68) or hospital stay (P = 0.2). Follow-up data
      were available for 66 patients, 36 of them with imaging. Follow-up imaging did
      not impact on clinical decisions and no late sequelae were identified.

PMID- 11527168
TI  - Splenectomy and splenic slice grafting in the management of thalassemia.
AB  - Over the last decade and a half, we performed a splenectomy along with slice
      grafting of the spleen in 170 (beta28 and Ebeta 142) transfusion-dependent, high
      risk thalassemic patients. Of these, 17 were selected for study of the fate of
      the grafts and their immune status before and after operation. The procedure had
      equally good advantages of splenectomy and immunoconservation as partial
      splenectomy, partial splenic embolization, or partial splenic dearterialization,
      if not better, but none of the disadvantages of the other procedures.

PMID- 11527169
TI  - Hydatid disease of the liver in childhood: the success of medical therapy and
      surgical alternatives.
AB  - Hydatid liver disease in children is a serious problem where the parasite is
      endemic. Although surgery is considered the treatment of choice, medical therapy
      is an alternative, but its curative efficacy is controversial. The aims of this
      study were to evaluate the curative efficacy of medical treatment and compare the
      results of surgical techniques with respect to postoperative complications in 102
      consecutive children (64 male and 38 female, aged 4 to 15 years, mean 8.15 years)
      treated in two children's hospitals between 1988 and 1997. In 67, medication with
      albendazole was used as the initial therapy; 17 had multiple hepatic cysts and 8
      had coexisting cysts in the lung. Success was defined as progressive shrinkage
      and solidification of the cyst. The overall success of medical therapy was
      approximately 27%: 18 of the 67 patients were cured with albendazole (15 had a
      single cyst, 3 multiple cysts) and 1 recurrence (6%) was observed. Age, sex, and
      the size, location, and number of cysts did not show any relationship to the
      response to medical therapy. After 12 to 14 weeks of medical treatment, a viable
      cyst on ultrasonography and/or computed tomography was accepted as a sign of
      treatment failure and these patients were scheduled for surgery. A total of 84
      patients (35 primarily, 49 after unsuccessful medical therapy) were treated
      surgically. Procedures included cystectomy and tube drainage in 11 patients,
      cystectomy in 17, cystectomy and capitonnage in 24, and cystectomy and
      omentoplasty in 32. The incidence of early postoperative complications was 55%
      for tube drainage, 18% for cystectomy, 13% for capitonnage, and 0% for
      omentoplasty. During the follow-up period, 2 surgical patients (2%) developed
      recurrent disease. Medical treatment with albendazole resulted in fewer curative
      successes than expected. A longer period of medical treatment may increase the
      success rate; this question requires further study. Omentoplasty decreased the
      rate of early postoperative complications, especially cavity abscess and biliary
      fistula, after surgical treatment and should be recommended in this setting.

PMID- 11527170
TI  - Extended hepatic resection with transplantation back-up for an "unresectable"
      tumour.
AB  - Liver transplantation (LT) for malignancy has had disappointing long-term results
      due to tumour recurrence. Ex-vivo dissection and auto-transplantation have had
      poor results when the tumor was obstructing bile ducts. Advances in liver surgery
      have made extensive liver resection safer, but cases of "unresectable" tumours
      due to site and size still present. A 10-year-old boy was referred with jaundice
      due to a 6 x 8-cm central (segment 4) tumour shown on biopsy to be a
      fibrolamellar hepatocellular carcinoma. Ultrasound (US) and Computed Tomography
      also showed dilatation of intrahepatic bile ducts in both lobes. Angiography
      showed a large tumour mass supplied by the left branch of the hepatic artery, a
      low take-off of a right branch of the hepatic artery, and a very displaced but
      patent portal vein. The initial surgical consensus was that the tumour was
      unresectable. The patient was listed for LT with the plan of first attempting
      resection with a liver graft-in-waiting. An extended left hepatectomy was
      performed under total vascular exclusion with resection of the tumour, which had
      extended from segment 4 into surrounding segments 1, 3, 5, and 8. Intraoperative
      US assisted in planning the resection. The right hepatic vein, artery, and the
      right branch of the portal vein could be preserved and a Roux loop was
      anastomosed to a markedly dilated segment 6 and 7 intrahepatic duct for bile
      drainage. Vascular exclusion time was 30 min. The patient made a good recovery
      without major complications. Jaundice and bile-duct dilatation resolved. On
      follow up at 5 years there was no recurrence. The liver graft-in-waiting gave the
      surgical team confidence to proceed with an extensive resection beyond a "point
      of no return" and allowed good clearance of the disease and avoidance of LT with
      all the long-term consequences of immunosuppression. This mandates that extensive
      hepatic surgery in children should be carried out in centres that have a facility
      for LT should the need arise.

PMID- 11527171
TI  - Open method versus capitonnage in management of hepatic hydatidosis in children.
AB  - Hepatic hydatid cysts (HHC) are not uncommon in children, and a large number of
      cases are treated surgically every year in Kashmir. Capitonnage is commonly used
      to deal with the residual pericyst cavity after enucleation of the endocyst, but
      its recognized major complications are hydrops and secondary infection in the
      residual cavity. In this randomized study, a prospective and retrospective
      evaluation was done to compare capitonnage with the open method of treating HHCs.
      In 42 children, group I (n = 23) treated by capitonnage and group II (n = 19)
      treated by the 'open' method, there was no mortality. Group II patients had a
      more rapid recovery and fewer postoperative complications as well as a shorter
      total hospital stay compared to group I patients.

PMID- 11527173
TI  - Bacterial cholangitis in patients with biliary atresia: impact on short-term
      outcome.
AB  - Bacterial cholangitis (BC) is a common complication in patients with biliary
      atresia (BA) and is characterized by fever, acholic stools and positive blood
      cultures. The diagnosis is often empirical because the yield of blood cultures is
      low. It is difficult to differentiate BC from other febrile episodes. In order to
      characterize the clinical and laboratory features of BC in patients with BA,
      identify risk factors, and correlate cholangitis with outcome, 37 patients with
      BA from 1993 to 1998 who underwent a Kasai operation in our hospital were
      studied. The follow-up period ranged from 6 to 59 months. A total of 107 febrile
      episodes were documented in these patients. The diagnostic criteria for
      cholangitis were fever, increased jaundice, or acholic stools. The clinical
      features, laboratory data, results of bacterial cultures, and outcomes were
      analyzed retrospectively. A total of 107 febrile episodes, including 78 bouts of
      cholangitis and 29 non-cholangitis infections, were found in 34 patients.
      Patients with BC had higher postoperative bilirubin levels (P = 0.02) and less
      frequent use of prophylactic antibiotics (P = 0.05) than those with non
      cholangitis infections. Abnormal white blood cell counts (> 12,000 or <4,000 mm3)
      tended to be present in patients with BC (P = 0.08). There were no statistical
      differences in the risk factors and laboratory data between culture-positive (n =
      16) and -negative (n = 62) cholangitis cases. The occurrence of cholangitis
      significantly reduced survival in both patients with good (P = 0.03) and
      inadequate bile flow (P = 0.03). All 9 patients who had never had cholangitis
      survived during the follow-up period. Repeated attacks of BC further decreased
      survival probability. The responsive organisms were mainly enteric bacteria,
      including Escherichia coli, Enterobacter cloacae, Klebsiella pneumoniae,
      Pseudomonas aeruginosa, Acinetobacter baumanni, and Salmonella typhi. The
      sensitivity tests justified empirical therapy with ceftriaxone. The effectiveness
      of prophylactic trimethoprim-sulfamethoxazole or neomycin warrants further
      studies. BC was a highly prevalent postoperative complication in patients with
      BA, especially those with inadequate bile drainage. It significantly affected
      early mortality. Aggressive and complete treatment with empirical ceftriaxone was
      appropriate.

PMID- 11527172
TI  - Beneficial effect of a traditional herbal medicine (inchin-ko-to) in
      postoperative biliary atresia patients.
AB  - Inchin-ko-to (ICKT) prevents Fas-mediated liver injury. This study evaluates the
      effect of ICKT on conventional markers of liver function (LF) and liver fibrosis
      in 18 postoperative biliary atresia (BA) patients aged 3 to 23 years with
      elevated glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase
      (GPT), gamma-glutamyl transpeptidase (gammaGTP) but normal serum total bilirubin
      (T-Bil) levels. ICKT (0.15 g/kg per day) was administered orally for 1 year.
      Serum GOT, GPT, gammaGTP, total bile acids (TBA), and T-Bil as markers of LF and
      hyaluronic acid (HA), prolyl hydroxylase (PH), procollagen III peptide (PIIIP),
      and type IV collagen as markers of liver fibrosis were measured before and after
      treatment in each patient and compared statistically. All patients tolerated ICKT
      well, and there were no side effects. The percentage of subjects who improved
      after ICKT was 45% for serum GOT, 72% for GPT, 72% for gammaGTP, 72% for TBA, 67%
      for HA, 40% for PH, 50% for PIIIP, and 23% for type IV collagen. Changes in the
      mean values of all serum markers were statistically significant (P < 0.01). It is
      concluded that long-term administration of ICKT in postoperative BA patients
      improves liver status as assessed by markers of LF and fibrosis.

PMID- 11527174
TI  - Outcome after laparoscopic cholecystotomy and cholecystectomy in children with
      symptomatic cholecystolithiasis: a preliminary report.
AB  - Laparoscopic cholecystectomy (LCE) has become the procedure of choice for
      symptomatic gallstones in children. However, there is concern about the
      disadvantages of cholecystectomy. Numerous postoperative symptoms and a possible
      correlation of the procedure with a higher incidence of right-sided colon
      carcinoma have been described. Therefore, it has been suggested to remove the
      gallstones via a cholecystotomy, leaving the gallbladder in place. This is the
      first report on the functional and symptomatic outcome of laparoscopic
      cholecystotomy (LCO) versus LCE in a consecutive series of children. A follow-up
      study of all children who underwent surgery for symptomatic gallstone disease
      from 1993 to 1999 was performed. Nine underwent LCO and 8 standard LCE. The
      procedure was chosen according to the preference of the surgeon. Patients and
      parents underwent a standardized follow-up interview. The intensitiy of six
      gastrointestinal symptoms was graded from 0 to 3. The patients and parents scored
      the symptomatic outcome using a 100-point visual analogue scale. There were no
      intraoperative complications. Bleeding of a port site required suturing in 1
      patient after LCO, and fever with a further uneventful course occurred in another
      after LCE. The mean duration of hospital stay was 3.0 days after LCO and 2.4 days
      after LCE. In 1 patient a missed gallstone was identified 4 weeks after LCO. The
      patient underwent LCE with a further uneventful course. At follow-up (mean 20.7
      months after LCO, 28.3 months after LCE, P = n.s.) there was a tendency toward a
      lower incidence of symptoms after LCO. Symptoms were reported by 3 of 8 patients
      after LCO and 5 of 8 after LCE. The mean score of the symptomatic outcome was not
      statistically different. All patients with LCO were free of stones on ultrasound
      examination with normal contraction of the gallbladder. LCO thus represents an
      alternative approach. We consider LCO for children with symptomatic
      cholecystolithiasis before the onset of puberty. However, data on the long-term
      outcome from larger series are mandatory before a general recommendation can be
      given.

PMID- 11527175
TI  - Carcinoid tumors of the appendix in children.
AB  - We report ten cases of carcinoid tumor of the appendix observed in children from
      1988 to 1996. The patients included six females and four males with an average
      age of 13 years at presentation. They were admitted after complaining of pain in
      the lower abdominal quadrant. In eight children who presented with symptoms of
      acute appendicitis, the tumor was located at the tip of the appendix. Diagnosis
      was performed after appendicectomy (AE) and pathologic examination, which
      revealed a tumor slightly under 1 cm in size. Two other children were admitted
      with clinical signs of peritonitis due to larger tumors measuring more than 2 cm
      on the base of the appendix. One patient underwent a cecectomy, the other a right
      hemicolectomy. For all patients follow-up was 3 years, and all recovered fully.
      According to these findings and a review of the literature, we suggest
      conservative surgical procedures in children. More than 70% of these tumors are
      localized at the tip of the appendix and represent an incidental pathologic
      finding during AE; AE alone is curative. Patients with a bulky tumor of the
      appendicular base measuring 2 cm and invading the serosa and mesoappendix without
      metastases may be treated with a cecectomy; ileocecal resection may be indicated
      in cases where the tumor has infiltrated tissue beyond the cecum with localized
      metastases and in patients with incomplete gross resection. Right hemicolectomy
      is questionable in this age group and restricted to rare conditions.

PMID- 11527177
TI  - Semicircular papillotomy: a new surgical technique for removal of bile stones
      lodged in the ampulla of Vater.
AB  - Bile stones lodged in the ampulla of Vater present a rare but often difficult
      problem. Considering the disadvantages of conventional papillotomy and
      papillectomy, we developed a technique in which both the anatomic structures and
      their function are preserved. Histologic studies of the ampulla provided the
      basis for the technique, in which the muscular layers of the ampulla are not cut
      through as in conventional papillotomy but are bluntly separated, preserving this
      important anatomic component of the ampulla saved. The postoperative and long
      term outcome of seven patients with bile stones lodged in the ampulla are
      reported. We found semicircular lateral papillotomy a safe procedure that
      preserves the muscular structures and function of the ampulla.

PMID- 11527176
TI  - Clinical appraisal of Ascaris lumbricoides, with special reference to surgical
      complications.
AB  - Over a period of 4 years (January 1993-December 1997), 509 patients were treated
      for abdominal colic with or without intestinal obstruction and a history of
      passage of adult roundworms either in the stool or in vomitus. All patients were
      below the age of 10 years, the youngest 6 months old, and were treated
      successfully with antispasmodics and normal saline enemas. When the pain
      subsided, an anthelminthic drug was given. Of 209 patients admitted to the
      hospital, 105 responded to conservative management and 104 (50%) required
      surgical intervention. The procedures included squeezing out of worms, resection
      and anastomosis, and treatment of other pathologies like acute appendicitis,
      tubercular stricture of the small intenstine, etc. Five patients died in the
      postoperative period due to various complications. There were no deaths among
      those treated by conservative management. Early recognition of the condition can
      prevent serious surgical complications and morbidity.

PMID- 11527178
TI  - Rectourinary fistula with a narrow urethra.
AB  - A rectourinary fistula is a common accompaniment of anorectal malformations (ARM)
      in boys. Most boys pass urine normally after reconstruction and closure of the
      fistula, but a few have serious problems because of a narrow urethra. In our
      series, a narrow urethra was encountered in three types of male ARM: 3
      rectourethral fistulae, 4 rectovesical fistulae, and 6 H-fistulae. We have
      studied the diagnostic and therapeutic problems that a narrow urethra produces in
      patients afflicted with each of these malformations.

PMID- 11527179
TI  - Outcome of pull-in procedure in children with severe post-disruption posterior
      urethral strictures.
AB  - A total of 17 children aged 5 to 15 years with the diagnosis of posttraumatic
      posterior urethral stricture were operated upon using a pull-in procedure during
      the last 9 years. Among the diagnostic tools, synchronous inspection of both the
      anterior and posterior urethra by cystoscopy yielded the most valuable
      information. A success rate of 70% was achieved with the procedure plus
      postoperative re-catheterization. A pedunculated tube prepared from the scrotal
      skin cured 2 patients after a series of failed operations. Difficult voiding
      occurring after removal of the stent due to an inappropriate pressure gradient
      created between the bladder neck and urethra usually benefits from short-term
      catheterization. Mild chordee was present in 1 patient. Ejaculation and erection
      were present in 3 children who reached puberty.

PMID- 11527180
TI  - The effect of the genitofemoral nerve division on the contralateral descended
      testis in the unilateral cryptorchidism model.
AB  - It is widely accepted that there are degenerative changes and decreased
      spermatogenesis in the contralateral descended testis (CDT) in unilateral
      undescended testis (UUDT). While some investigators have postulated that the
      mechanism may be related to primary (congenital) or secondary (autoimmune,
      vascular, and neural) events, the exact mechanism of the damage to the CDT is
      still unknown. The present study was planned to investigate the role of the
      genitofemoral nerve (GFN) on the changes in the CDT. Forty male Wistar albino
      rats were divided into four groups of 10 each. During the newborn period a UUDT
      model was created and at the age of 30 days ipsilateral GFN division was done
      (group A). In addition, UUDT with intact GFN (group B), divided right GFN with
      bilateral scrotal testes (group C), and control (group D) groups were formed.
      When the animals reached early adulthood, they were killed and the testes were
      removed. Mean seminiferous-tubular diameter (STD) and germinal-ephitelium
      maturity was determined using modified Johnson testicular biopsy scores (TBS).
      The mean STD and TBS of the study groups did not show any differences suggesting
      that ipsilateral division of the GFN has no effect on the CDT in the UUDT model.

PMID- 11527181
TI  - The ascending testis: is late orchidopexy due to failure of screening or late
      ascent?
AB  - It is widely recommended that infant boys with undescended testes (UDT) should be
      referred for surgical opinion before the age of 18 months. To attempt to identify
      the reasons why the mean age at orchidopexy in our institution was as high as 5.5
      years, a retrospective review of the screening history, examinations, and
      management of boys over the age of 3 years at the time of orchidopexy was
      undertaken by reference to community, general practitioner, and hospital records.
      In 36 children where hospital and community records giving information prior to
      referral were available, the UDT had previously been documented on at least one
      occasion as descended in 24 children or retractile in 10. In 1 child there was
      delayed referral, and in another, there was operative delay. It is concluded that
      there is either frequent failure of the Child Health Surveillance screening
      programme, or that late ascent of a testis previously sited in the scrotum is a
      common occurrence. We recommend further prospective studies to clarify this
      latter phenomenon.

PMID- 11527182
TI  - The history of spina bifida, hydrocephalus, paraplegia, and incontinence.
AB  - This paper covers the history since ancient times of spina bifida (SB) and its
      main associated conditions, viz., hydrocephalus, paraplegia and incontinence.
      Particular stress has been placed on the ancient authors who recognised these
      conditions. The article concludes with the history of some general aspects of SB
      and the dilemmas in its treatment.

PMID- 11527183
TI  - Central-venous access through the peripheral route in surgical neonates: an audit
      of 125 consecutive lines from a regional neonatal centre.
AB  - A long Percutaneous silastic IV line is frequently used in surgical neonates for
      infusion of hyperosmolar parenteral nutrition fluid into a central vein for
      several days without the need for operative insertion of a Broviac catheter or
      risks of direct puncture of a central vein. Our study was aimed at auditing the
      performance of 125 consecutive lines over a 2-year period. During this period,
      insertion was attempted in 125 babies; in 13 cases the line could not be inserted
      because of technical problems. The gestational ages varied between 25 and 41
      weeks and weights between 630 g and 4.2 kg. Success did not appear to be related
      to the age or weight of the baby. The mean duration of complication-free
      performance was 22.4 days. There was a significant difference between the
      complication rate of lines inserted in the operating theatre versus those on the
      ward (P < 0.05). There was no significant increase in complications in lines used
      for over 4 weeks. The technique adopted by us for inserting these lines is likely
      to succeed in the majority of cases, including premature and small-for-dates
      babies. In our experience, lines inserted in the controlled theatre environment
      either before or after abdominal surgery performed better. The manufacturer's
      recommendation to electively change the line every 4 weeks needs further
      prospective evaluation.

PMID- 11527184
TI  - Telemedicine in pediatric surgery.
AB  - Telemedicine is a new academic specialty at the crossroads of medical informatics
      whose potential is still largely untapped by pediatric surgeons. Telemedicine
      aims to alleviate travel concerns associated with the delivery of health care, to
      bring expert pediatric surgeons to areas where currently none exist, and to
      improve coordination between pediatric surgeons, transcending all barriers.
      Today, it is possible to transmit all digitized data--roentgenograms,
      echocardiograms, radiologic images, intraoperative photographs, histologic
      images, etc., and to consult specific experts in the subspecialties of childcare.
      It is possible to train and guide surgical trainees by experts without their
      physical presence. In the future, telemedicine will constitute an integral part
      of the health care of children and the training of pediatric surgeons.

PMID- 11527185
TI  - Pediatric surgery in sub-Saharan Africa.
AB  - Pediatric surgery in sub-Saharan Africa is disadvantaged by the large number of
      sick children, disease patterns specific to the region, late presentation, and
      advanced pathology. In addition, it is practiced in an environment of limited
      resources and facilities and other health priorities. Obstacles to better
      pediatric-surgical care (PSC) include a general lack of interest in surgical
      conditions affecting African children, its poorly defined role, and a lack of
      political commitment by governments and international agencies to see surgical
      care of children improve. Pediatric-surgical practice in Africa must be cognizant
      of the factors that limit delivery of surgical services and work toward
      developing cost-effective strategies that benefit the largest number of children.
      Demonstrating that childhood surgical conditions are a significant public health
      care problem is the most likely way to change health-care policy and to ensure
      adequate resources for PSC. Other priorities should be to define a cost-effective
      package of pediatric surgical services, improve PSC at the community level, and
      strengthen pediatric surgical-education.

PMID- 11527187
TI  - Agenesis of the skull bones.
AB  - Agenesis of the cranial bones, a rare condition usually incompatible with life,
      was seen in a neonate. Embryogenesis and management of the condition are
      discussed. The defect heals with conservative treatment.

PMID- 11527186
TI  - Emergency neonatal surgery in a developing country.
AB  - With better understanding of neonatal physiology and improvements in diagnostic
      facilities and neonatal intensive care units (NICU), the outcome of neonatal
      surgery has improved in developed countries. In developing countries, however,
      neonatal surgery is problematic, particularly in the emergency setting, but there
      are few reports from these countries. A retrospective analysis of 154 neonates
      who had emergency surgery over a 10-year period at the Ahmadu Bello University
      Teaching Hospital, Zaria, Nigeria, was undertaken. Emergency surgery represented
      40% of surgical procedures in neonates in the hospital. The majority of the
      patients (94.8%) were delivered at home or in rural health centers. The median
      weight was 2.7 kg (range 2.0-3.7 kg). In 89 cases (58%) the indications for
      surgery were intestinal obstruction, anorectal malformations in 60(67%) and in
      33(21%) complicated exomphalos or gastroschisis. Nine patients (6%) required
      surgery for ruptured neural-tube defects. A colostomy was the commonest procedure
      (51, 33%), 27(53%) of which were performed using a local anesthetic without
      adverse effects. Thirty-three abdominal-wall defects were closed by various
      methods (fascial closure 23, skin closure 6, improvised silo 4). Overall, 37
      (24%) procedures were performed using local anesthesia. Fifty-nine patients (38%)
      developed postoperative complications (infections 33, respiratory insufficiency
      16, colostomy complications 8, anastomotic leak 2). The mortality was 30.5%, 66%
      due to overwhelming infection, 28% to respiratory insufficiency, and 4.3% to
      multiple anomalies. Other factors considered to have contributed to morbidity and
      mortality were late referral and presentation and a lack of NICUs. Thus,
      emergency neonatal surgery is attended by high morbidity and mortality in our
      environment at the present time. Early referral and presentation and provision of
      NICUs should improve the outcome.

PMID- 11527188
TI  - Three-dimensional pressure imaging: a novel method for intraoperative manometry
      during laparoscopic esophagomyotomy for esophageal achalasia.
AB  - With the introduction of computerized manometry, the creation of the three
      dimensional (3-D) pressure image with measurement of pressure vector volume (PVV)
      has become available to assess the pressure structure of the high-pressure zone
      (HPZ) of the distal esophagus. We have applied this technique to intraoperative
      manometry during laparoscopic surgery for esophageal achalasia (EA). A
      laparoscopic esophagomyotomy with anterior fundoplication was performed in a 12
      year-old boy with EA. Computerized 3-D images were obtained by a stepwise
      pullback of a manometric assembly with eight radial side-holes to quantitate the
      PVV of the HPZ of the distal esophagus in each stage of the operation for EA.
      Virtual abolishment of the peak pressure image and a marked reduction in the PVV
      after esophagomyotomy suggested appropriate decompression of the HPZ.
      Intraoperative manometry using computerized 3-D pressure imaging with measurement
      of the PVV is thus useful to assess the HPZ during laparoscopic surgery for EA.

PMID- 11527189
TI  - Herniation through triple defects of the diaphragm with gastric volvulus.
AB  - A rare case of herniation through triple defects in the diaphragm with volvulus
      of the stomach is reported. Herniation with gastric volvulus was diagnosed
      preoperatively. Three diaphragmatic defects were detected at surgery. Repair of
      the defects after reduction of the abdominal contents resulted in an uneventful
      recovery.

PMID- 11527190
TI  - Ectopic intrathoracic liver.
AB  - Accessory hepatic tissue, unlike accessory splenic and pancreatic tissue, is rare
      and has a limited and almost exclusively sub diaphragmatic distribution. Fewer
      than ten cases of intrathoracic ectopic liver have been reported so far in the
      literature. This paper reports a case that caused a diagnostic dilemma.

PMID- 11527191
TI  - Spontaneous perforation of the extrahepatic bile duct in an infant.
AB  - A 1.2-year-old male presented with gradual-onset biliary ascites, mild icterus,
      and failure to thrive due to spontaneous bile-duct perforation (SPBD) confirmed
      by technetium 99Tc HIDA scan and abdominal paracentesis. Peritoneal tube drainage
      for 2 weeks helped the perforation to seal spontaneously, as there was no distal
      obstruction. No surgery was needed. Only less than 100 cases of SPBD have been
      reported in the English literature. The pathogenesis and treatment options are
      reviewed and discussed.

PMID- 11527192
TI  - Wilms' tumor arising in a horseshoe kidney.
AB  - The incidence of horseshoe kidney (HK) is estimated at 1 in 400 cases. The
      occurrence of Wilms' tumor (WT) in a HK is an uncommon event, estimated at 0.4%
      0.9% of all WTs. We report a case of WT arising from the isthmus of a HK and
      review the literature on the subject.

PMID- 11527193
TI  - Neonatal intestinal obstruction from solitary intestinal fibromatosis.
AB  - Solitary intestinal fibromatosis (SIF) is a very rare condition, with only 13
      cases reported. We present a new case of SIF causing neonatal intestinal
      obstruction and review the literature on this condition. SIF appears to be a
      condition of infancy and carries a very good prognosis after segmental resection.

PMID- 11527194
TI  - Application of the Malone antegrade continence enema principle in degenerative
      leiomyopathy.
AB  - An 1-year-old boy with degenerative leiomyopathy (DL) presented with a volvulus
      of the transverse colon. After derotating the volvulus, we constructed a tube
      colostomy (TC) from the transverse colon. This TC has been used for the past 2
      years by the patient for regular deflation of the colon and antegrade colonic
      enemas (ACE). We present this as a preliminary report of the use of the Malone
      ACE procedure in a patient with DL and review the relevant literature.

PMID- 11527195
TI  - Junctional epidermolysis bullosa lethalis with pyloric and anorectal obstruction.
AB  - The authors present a case of epidermolysis bullosa lethalis (EBL) associated
      with a double obstruction, one at the pyloric and the other in the anorectal
      region. Both obstructions could be due to separation of the rectal mucosa during
      intrauterine life followed by adhesive closure of its wall. Both the
      gastrointestinal lesions could be part of the generalized denudation process
      involved in EBL.

PMID- 11527196
TI  - Adenocarcinoma of the colon as a second malignancy in a child.
AB  - Solid tumors as second malignancies are not common in children who have been
      managed for lymphoproliferative disorders. We report a case of adenocarcinoma
      (AC) of the colon as a second malignancy in a patient who was on maintenance
      chemotherapy for acute lymphoblastic leukemia (ALL). In children, primary AC of
      the colon is very rare; colonic AC occurring as a second malignancy in a child is
      rarer still. A case of AC of the colon following chemotherapy for ALL has not yet
      been published.

PMID- 11527198
TI  - Epigastric heteropagus twins--a report of four cases.
AB  - Asymmetrical conjoined twinning is an extremely rare congenital anomaly
      constituting only 1%-2% of all conjoined twins. In epigastric heteropagus twins
      (EHT), the dependent portion (parasite) is smaller than the host (autosite). The
      embryopathy is related to incomplete cleavage of the embryo at 2 weeks of
      gestation. However, some form of ischaemic insult in early gestation leads to
      selective atrophy of the cranial part of one of the monozygous twins. We report
      our experience with four cases of EHT and a review of the literature with a
      discussion of possible embryopathy.

PMID- 11527197
TI  - Recurrent cervical abscess: life-threatening presentation of chronic
      granulomatous disease in twin infants.
AB  - Non-identical male twins presented at 12 and 13 weeks of life, respectively, with
      recurrent cervical abscesses and signs of imminent upper-airway obstruction
      (UAO). Despite adequate initial surgical drainage, airway patency became
      seriously jeopardised in both cases by recurrent abscess formation requiring
      further intervention. Chronic granulomatous disease was eventually diagnosed in
      both cases. The unusual presentation of this rare condition with life-threatening
      UAO in twin infants, a scenario not previously described, is reported and a
      management protocol suggested.

PMID- 11527199
TI  - Fetus in fetu: report of an additional, well-developed case.
AB  - An 8-month-old boy presenting with a fast-growing abdominal mass was operated
      upon to remove the tumor, which was confirmed to be a well-formed fetus in fetu.
      The authors describe the clinical, radiologic, and surgical findings and review
      the literature.

PMID- 11527200
TI  - Limb-body wall complex: a compound anomaly pattern in body-wall defects.
AB  - Our presentation of four cases demonstrates the essential features of limb-body
      wall complex (LBWC), representing a compound anomaly pattern in body-wall
      defects. The diagnosis of this entity is based on two of the three following
      characteristics: (1) exencephaly/encephalocele and facial clefts; (2) thoraco-
      and/or abdominoschisis; and (3) limb defects. A definite association with
      internal anomalies and severe kyphoscoliosis makes a more distinct concept of the
      pathogenesis reasonable. Limb-body wall malformations result from a malfunction
      of the ectodermal placodes involving the early embryonic folding process. The
      poor prognosis of LBWC calls for early antenatal diagnosis.

PMID- 11527201
TI  - Mesh hiatal reinforcement in Nissen fundoplication.
AB  - Persistent or recurrent gastro-oesophageal reflux (GOR) following Nissen
      fundoplication occurs in up to one in five cases, especially if the child is
      neurologically impaired. We advocate the use of mesh hiatal reinforcement for
      patients undergoing reoperation for GOR or if the diaphragmatic crura are thought
      to require reinforcement at the time of the original surgery.

PMID- 11527202
TI  - Laparoscopic colonic mapping of dysganglionosis.
AB  - Retention of a proximal aganglionic segment or the unrecognized coexistence of
      other dysganglionoses may jeopardize the definitive surgical treatment of
      Hirschsprung's disease (HD). To assess the extent of the disease and/or the
      presence of other dysganglionoses without an additional laparotomy, we developed
      a laparoscopic-assisted technique to perform colonic full-thickness biopsies.
      After creation of a pneumoperitoneum, a 5-mm laparoscope is inserted in the
      supraumbilical area and a working 10/12-mm port is placed in the left iliac
      fossa. The sigmoid/descending colon is grasped and pulled through the abdominal
      wall and a full-thickness biopsy done. The same procedure is applied to the
      transverse and ascending colon. Rectal and colonic biopsy specimens were studied
      using enzyme histochemical methods. Over the last year, five children aged 7
      months to 12 years with dysganglionosis underwent laparoscopic-assisted mapping
      of the colon. Previous rectal suction biopsies were diagnostic of HD in three
      patients and suspicious of hypoganglionosis in two. Proximal full-thickness
      biopsies revealed: normal colon in two cases of HD; coexistent type B intestinal
      neuronal dysplasia up to the descending colon in the other case of HD; and
      hypoganglionosis up to the ascending colon in the two patients with suspected
      hypoganglionosis. The procedures were performed easily, the patients being
      discharged after 36 to 48 h with no complications. Four children have already
      undergone pull-through procedures with resection of the affected colon in
      adhesion-free abdominal cavities and did not develop constipation or
      enterocolitis. Laparoscopic-assisted mapping of the entire colon is a simple,
      safe, and effective procedure that may contribute to improving the outcome of
      intestinal dysganglionosis by better characterization of the disease.

PMID- 11527203
TI  - Hypospadias repair using a double onlay preputial flap.
AB  - From an anatomical view, a more reasonable blood supply can be achieved in
      hypospadias repair using a double-faced onlay flap. A urethroplasty was performed
      in 15 patients with middle or posterior hypospadias using a double-faced onlay
      preputial flap (DOPF). In this method, the urethral plate is preserved and a
      double-faced preputial flap is developed. The inner face of the flap is sutured
      to the urethral plate to create the neourethra and the outer face together with
      the rest of the dorsal prepuce is used for ventral skin coverage. Postoperative
      complications occurred in 2 patients: 1 developed a fistula in the subcoronal
      region and 1 had dorsal skin necrosis and suture disruption of the glanular
      wings. The overall complication rate was 13%. The DOPF provides a well
      vascularized ventral skin cover and reduces the area of avascular dorsal skin.
      The viability of the neourethra can be evaluated by simply looking at the outer
      face of the flap. However, the complication rate is similar to that of other
      techniques.

PMID- 11527204
TI  - Reappraisal of the role of the bilioenteric conduit (BEC) in the pathogenesis of
      postoperative cholangitis.

PMID- 11527205
TI  - Vanishing gut in infants with gastroschisis.

PMID- 11527206
TI  - Anterior ectopic anus: an accurate definitive term for choice of treatment?

PMID- 11527207
TI  - An adriamycin experimental rat model inducing a wide variety of abnormalities
      similar to VACTERL association in humans is now well established.

PMID- 11527208
TI  - Array analysis of the genes regulated during neuronal differentiation of human
      embryonal cells.
AB  - Recent advances in genetic technology have provided a new platform on which the
      simultaneous analysis of a large number of genes is possible in a rapid and
      efficient fashion. To assess the differential expression of human genes during
      neuronal differentiation, we compared the transcript profiles of
      undifferentiated, partially differentiated, and fully differentiated NT2/D1
      cultures with cDNA expression arrays. Approximately 75 genes (13% of the gene
      array pool) were differentially expressed during neuronal development of NT2/D1
      cells. Genes coding for pyruvate kinase M2 isozyme, clathrin assembly proteins,
      calmodulin, fibronectin, laminin, thymosin beta-10, and many others were
      upregulated as NT2/D1 cells differentiated into neurons. In contrast, several
      kinases, phosphatases, and G-protein coupled receptor genes showed downregulation
      upon neuronal differentiation. The information provided here is an invaluable
      reference for characterizing the phenotype of these cells. This information can
      also be used in cell therapy and transplantation in which the graft
      microenvironment and interaction with the host tissue is crucial.

PMID- 11527209
TI  - beta1 Integrin-extracellular matrix protein interaction modulates the migratory
      response to chemokine stimulation.
AB  - It is well established that chemokines have a major role in the stimulation of
      cell movement on extracellular matrix (ECM) substrates. However, it is also clear
      that ECM substrates may influence the ability of cells to undergo migration.
      Using the migration chamber method, we assessed the migratory response of human
      embryonic kidney-293 (HEK) transfectant cells expressing the CC chemokine
      receptor 5 (CCR5) (HEK-CCR5) to stimulation by chemokines (macrophage inflamatory
      protein (MIP)-1alpha, MIP-1beta, and regulated on activation normal-T cell
      expressed and secreted (RANTES)) on ECM substrates (collagen type I and
      fibronectin). Using filters coated with collagen (20 microg/mL), results showed
      that the chemokines differed in their ability to elicit cell movement according
      to the order MIP-1beta > RANTES MIP-1alpha. In contrast, using filters coated
      with fibronectin (20 microg/mL), all three chemokines were similar in their
      ability to stimulate migration of HEK-CCR5 cells. In addition, the migratory
      response with respect to the concentrations of ECM substrates appeared biphasic:
      thus, chemokine-stimulated cell movement was inhibited at high ECM concentrations
      (100 microg/mL). To determine the involvement of beta1 integrins, results showed
      that the migratory response to chemokine stimulation on collagen was largely
      inhibited by monoclonal antibody (mAb) to alpha2beta1; however, complete
      inhibition required a combination of mAbs to alpha1beta1 and alpha2beta1. In
      comparison, migration on fibronectin was inhibited by mAb to alpha3beta1 and
      alpha5beta1. Our results suggest that the migratory response to CCR5 stimulation
      may vary quantitatively with both the CCR5 ligand (MIP-1alpha, MIP-1beta, and
      RANTES), as well as the nature and concentration of the ECM substrate involved.

PMID- 11527211
TI  - Palmitic acid uptake by the rat soleus muscle in vitro.
AB  - Abstract: The rate of fatty acid uptake, oxidation, and deposition in skeletal
      muscles in relation to total and unbound to albumin fatty acids concentration in
      the medium were investigated in the incubated rat soleus muscle. An
      immunohistochemical technique was applied to demonstrate whether the albumin
      bound fatty acid complex from the medium penetrates well within all areas of the
      muscle strips. It was found that the percentage of incorporation of palmitic acid
      into intramuscular lipids was fairly constant, independently of the fatty acid
      concentration in the medium, and amounted to 63-72% for triacylglycerols, 7-12%
      for diacylglycerols-monoacylglycerols, and 19-26% for phospholipids. Both
      palmitic acid incorporation into the muscle triacylglycerol stores and its
      oxidation to CO2 closely correlated with an increase in both total and unbound to
      albumin fatty acid concentrations in the incubation medium. Under conditions of
      increased total but constant unbound to albumin palmitic acid concentrations, the
      incorporation of palmitic acid into triacylglycerols and its oxidation to CO2
      were also increased, but to a lower extent. This supports the hypothesis that the
      cellular fatty acid metabolism depends not only on the availability of fatty
      acids unbound to albumin, but also on the availability of fatty acids complexed
      to albumin.

PMID- 11527210
TI  - Intermediate filaments modulation in an in vitro model of the hepatic stellate
      cell activation or conversion into the lipocyte phenotype.
AB  - Hepatic stellate cells are intralobular connective tissue cells expressing the
      myofibroblast or the lipocyte phenotypes. They participate in homeostasis of the
      liver extracellular matrix, repair, regeneration, and fibrosis under the former
      phenotype, and control the retinol metabolism, storage, and release under the
      latter one. They are heterogeneous in terms of their tissue distribution,
      function, and expression of cytoskeletal proteins. We have studied the
      expressions of intermediate filaments in the cloned GRX cell line representative
      of murine hepatic stellate cells, by immunolabeling, reverse transcription
      polymerase chain reaction (RT-PCR), immunoprecipitation and Western blots. GRX
      cells expressed vimentin, desmin, glial fibrillary acidic protein (GFAP), and
      smooth muscle alpha actin (SM-alphaA). Vimentin, desmin, and SMN-alphaA were
      expressed in all cultures. GFAP showed a heterogeneous intensity of expression
      and did not form a filamentous cytoskeletal network, showing a distinct punctuate
      cytoplasmic distribution. When activated by inflammatory mediators, GRX cells
      increased expression of desmin and GFAP. Retinol-mediated induction of the
      lipocyte phenotype elicited a strong decrease of intermediate filament protein
      expression and the collapse of the filamentous structure of the cytoskeleton.
      Quiescent hepatic stellate precursors can respond to physiologic or pathologic
      stimuli, expressing activated myofibroblast or lipocyte phenotypes with distinct
      patterns of cytoskeleton structure, metabolic function, and interaction with the
      tissue environment.

PMID- 11527212
TI  - Contact-activated migration of melanoma B16 and sarcoma XC cells.
AB  - During migration, tumour cells interact with neighbouring neoplastic and normal
      host cells, and such interaction may influence their motile activity. We
      investigated the effect of homotypic collisions on the motile activity of two
      tumour cell lines, mouse melanoma B16 and rat sarcoma XC, and nontransformed
      human skin fibroblasts. It was found that the tumour cells show only limited
      motile activity when moving as single cells without contact with neighbours. At a
      higher density of the culture (and also at a greater number of cell to cell
      contacts) the activation of motility of investigated tumour cells was observed.
      On the other hand, the normal human skin fibroblasts showed a typical reaction of
      density-dependent inhibition of motility. The motile activity of tumour cells was
      not affected by conditioned media and was visibly dependent on a direct physical
      contact among colliding cells. The activation of cell movement was observed about
      40-50 min after the initial contact between tumour cells. Contact-activated
      migration of neoplastic cells was inhibited by 50 microM verapamil (a selective
      voltage-gated calcium channel inhibitor) and 10 microM gadolinium chloride (a
      nonspecific blocker of mechanosensitive ion channels) but not by pertussis toxin.
      The observation that homotypic collisions among tumour cells strongly increase
      their motile activity suggests that contact-activated migration may play a
      significant role in tumour invasion and metastasis.

PMID- 11527213
TI  - Yap1 overproduction restores arsenite resistance to the ABC transporter deficient
      mutant ycf1 by activating ACR3 expression.
AB  - Ycf1 and Acr3 are transporters that have been previously shown to protect
      Saccharomyces cerevisiae cells from the toxic effects of arsenite. Ycf1 and Acr3
      are positively regulated by distinct, but related bZIP transcriptional
      activators, Yap1 and Yap8, respectively. In this study, we show that
      overexpression of Yap1 complemented the arsenite hypersensitivity of the ycf1
      null mutant, but only if the ACR3 gene is functional. We further show that the
      expression of either an ACR3-lacZ promoter fusion reporter or the endogenous ACR3
      gene was stimulated by the overproduction of Yap1 upon exposure to arsenite.
      These data suggest that Yap1 confers arsenite resistance to the ycf1 null mutant
      by activating expression of the Yap8-dependent target gene, ACR3. Our data also
      show Yap8-dependent ACR3-lacZ expression was greatly stimulated by arsenite in a
      dose-dependent manner in the parental strain. However, overproduction of Yap1 in
      the parental strain severely limited dose-dependent activation of the reporter by
      arsenite. We conclude that Yap1 may compete with Yap8 for binding to the ACR3
      promoter, but is unable to act as a potent activator.

PMID- 11527214
TI  - Helicobacter pylori from asymptomatic hosts expressing heptoglycan but lacking
      Lewis O-chains: Lewis blood-group O-chains may play a role in Helicobacter pylori
      induced pathology.
AB  - Helicobacter pylori is a widespread Gram-negative bacterium responsible for the
      onset of various gastric pathologies and cancers in humans. A familiar trait of
      H. pylori is the production of cell-surface lipopolysaccharides (LPSs; O-chain -
      > core --> lipid A) with O-chain structures analogous to some mammalian histo
      blood-group antigens, those being the Lewis determinants (Lea, Leb, Lex, sialyl
      Lex, Ley) and blood groups A and linear B. Some of these LPS antigens have been
      implicated as autoimmune, adhesion, and colonization components of H. pylori
      pathogenic mechanisms. This article describes the chemical structures of LPSs
      from H. pylori isolated from subjects with no overt signs of disease.
      Experimental data from chemical- and spectroscopic-based studies unanimously
      showed that these H. pylori manufactured extended heptoglycans composed of 2- and
      3-linked D-glycero-alpha-D-manno-heptopyranose units and did not express any
      blood-group O-antigen chains. The fact that another H. pylori isolate with a
      similar LPS structure was shown to be capable of colonizing mice indicates that
      H. pylori histo-blood-group structures are not an absolute prerequisite for
      colonization in the murine model also. The absence of O-chains with histo-blood
      groups may cause H. pylori to become inept in exciting an immune response.
      Additionally, the presence of elongated heptoglycans may impede exposure of
      disease-causing outer-membrane antigens. These factors may render such H. pylori
      incapable of creating exogenous contacts essential for pathogenesis of severe
      gastroduodenal diseases and suggest that histo-blood groups in the LPS may indeed
      play a role in inducing a more severe H. pylori pathology.

PMID- 11527215
TI  - Characterization of matrix metalloprotease activities induced in the sea urchin
      extraembryonic matrix, the hyaline layer.
AB  - Hyaline layers, freshly prepared from one-hour-old embryos, were devoid of
      gelatin-cleavage activity. However, upon storage at 4 degrees C, gelatin-cleavage
      activities appeared; three species of apparent mol mass 94 --> 117-, 90-, and 45
      kDa were seen. All three species required zinc for activity. Using gel-exclusion
      chromatography we separated the 94 --> 117-, and 90-kDa species from the 45-kDa
      activity. The two higher mol mass species were inhibited by ethylenebis
      (oxyethylenenitrilo) tetraacetic acid and the lost activity was restored by
      calcium. Reconstitution of activity occurred with an apparent dissociation
      constant (calcium) of 5 microM. The presence of millimolar concentrations of
      magnesium had a minimal inhibitory effect on activity. The thermal denaturation
      profile of the higher mol mass gelatin-cleavage activity was significantly
      different in the presence and absence of calcium. Stabilization of these
      activities against thermal denaturation at 60 degrees C occurred with an apparent
      dissociation constant (calcium) of 0.6 mM. Magnesium had no significant effect on
      the thermal denaturation profile. Collectively, these results suggest at least
      two different modes of interaction between calcium and the higher mol mass
      gelatinases. These conclusions are discussed in the context of the high calcium
      and magnesium concentrations present in the sea water environment of the sea
      urchin embryo.

PMID- 11527216
TI  - Processing of the insulin-like growth factor-II-mannose 6-phosphate receptor in
      isolated liver subcellular fractions.
AB  - A truncated, soluble form of the insulin-like growth factor-II-mannose 6
      phosphate (IGF-II-M6P) receptor has been identified in serum and shown to be
      released from cultured tissues and cells, liver being the main contributor to
      serum receptor in adult rats. In the present study, the processing of the IGF-II
      M6P receptor has been characterized in isolated liver subcellular fractions using
      ligand binding, affinity crosslinking, and Western immunoblotting techniques. The
      receptor in plasma membrane fractions differed from that in Golgi-endosomal
      fractions by: (i) a lower molecular size upon reducing polyacrylamide gel
      electrophoresis (245 vs. 255 kDa); (ii) a less tight membrane association as
      judged upon extractibility by NaCI; and (iii) the inability to recognize antibody
      anti-22C, directed against the cytoplasmic domain of the receptor. Incubation of
      cell fractions at 30 degrees C led to a pH- and time-dependent release of the
      receptor into the medium. The pH optimum for release was 5.5 in the Golgi
      endosomal fraction and 7.5 in plasma membrane fractions; at this pH,
      approximately 2% and 20%-30% of total receptors were released per hour,
      respectively. Receptor release was inhibited in a dose-dependent manner by
      aprotinin, benzamidine, and leupeptin in the Golgi-endosomal fraction, and by
      1,10 phenanthroline in plasma membrane fractions, although high concentrations
      were required for inhibition. The receptor released from Golgi-endosomes showed a
      5-10 kDa reduction in size and a loss of ability to recognize antibody anti-22C,
      but that released from plasma membranes showed little or no changes in size. We
      conclude that soluble, carboxy-terminally truncated forms of the IGF-II-M6P
      receptor are generated from the intact receptor in isolated Golgi-endosomal and
      plasma membrane fractions. However, receptor processing in these fractions
      exhibits different properties, suggesting the involvement of different proteases.

PMID- 11527217
TI  - Folding pathway for partially folded rabbit muscle creatine kinase.
AB  - Rabbit muscle creatine kinase (CK) was modified by 5,5'-dithio-bis(2-nitrobenzoic
      acid) accompanied by 3 M guanidine hydrochloride denaturation to produce a
      partially folded state with modified thiol groups. The partially folded CK was in
      a monomeric state detected by size exclusion chromatography, native
      polyacrylamide gel electrophoresis, circular dichroism, and intrinsic
      fluorescence studies. After dithiothreitol (DTT) treatment, about 70% CK activity
      was regained with a two-phase kinetic course. Rate constants calculated for
      regaining of activity and refolding were compared with those for CK modified with
      various treatments to show that refolding and recovery of activity were
      synchronized. To further characterize the partially folded CK state and its
      folding pathway, the molecular chaperone GroEL was used to evaluate whether it
      can bind with partly folded CK during refolding, and 1-anilinonaphthalene-8
      sulfonate was used to detect the hydrophobic surface of the monomeric state of
      CK. The monomeric state of CK did not bind with GroEL, although it had a larger
      area of hydrophobic surface relative to the native state. These results may
      provide different evidence for the structural requirement of GroEL recognition to
      the substrate protein compared with previously reported results that GroEL bound
      with substrate proteins mainly through hydrophobic surface. The present study
      provides data for a monomeric intermediate trapped by the modification of the SH
      groups during the refolding of CK. Schemes are given for explaining both the
      partial folding CK pathway and the refolding pathway.

PMID- 11527218
TI  - Deglycosylated ceruloplasmin maintains its enzymatic, antioxidant,
      cardioprotective, and neuronoprotective properties.
AB  - Ceruloplasmin (CP), an important serum antioxidant, is a blue copper glycoprotein
      with ferroxidase and oxidase activities. Among other physiological actions,
      plasma CP was shown to protect isolated rat hearts and cultured P19 neurons
      exposed to oxidative stress conditions, raising the possibility of using this
      protein in the treatment of cardiac and neuronal diseases related to oxidative
      damage. However, since therapeutic applications of CP must be compatible with
      restrictions in the administration of blood derivatives to humans, there is a
      need to produce the protein by genetic engineering. To help in the choice of
      adequate expression systems, we undertook this study to determine if the
      carbohydrate moiety on the protein is essential for its functions. CP was
      completely deglycosylated using N-glycosidase F under nondenaturing conditions.
      Deglycosylated CP was found to retain most of the conformational, antioxidant,
      and enzymatic properties of the native protein in vitro. Moreover, both forms of
      the protein had similar cardioprotective and neuronoprotective effects against
      oxidative stress as evaluated with isolated rat hearts undergoing ischemia
      reperfusion and with cultured P19 neurons exposed to xanthine-xanthine oxidase.
      The data thus indicate that the carbohydrate moiety of CP is not essential for
      its enzymatic and protective actions. Accordingly, even the use of expression
      systems that do not glycosylate mammalian proteins could provide a recombinant CP
      that retains its therapeutic potential.

PMID- 11527219
TI  - Purification and characterization of cholesterol sulfotransferase from rat skin.
AB  - Previous work has demonstrated that the activity of the enzyme cholesterol
      sulfotransferase is rapidly and dramatically increased upon squamous
      differentiation of a variety of epithelial cells in culture, including epidermal
      keratinocytes. As a step toward understanding the molecular mechanisms underlying
      this differentiation-related change, we now report the partial purification and
      characterization of this enzyme activity from rat skin. Supernatant solutions
      from rat skin homogenates were subjected to a series of column chromatography
      steps including anion exchange, gel filtration, chromatofocusing and hydrophobic
      interaction chromatography. The purification procedure resulted in cholesterol
      sulfotransferase activity purified 2,700-fold with a 11% recovery. The most
      purified preparation yielded a major Coomassie blue-stained band on denaturing
      polyacrylamide gel electrophoresis of an apparent molecular weight (MW) of 40,000
      Da. Photoaffinity labeling with the donor substrate, 3'-phosphoadenosine-5'
      phospho-[35S]-sulfate resulted in a single radiolabeled protein band on
      denaturing polyacrylamide gel electrophoresis, again of apparent MW 40,000 Da,
      strongly suggesting that the major Coomassie blue-stained band in the most
      purified preparation is the cholesterol sulfotransferase protein. Among 3beta
      hydroxysteroids with a A5 double bond that were tested, each served as a
      substrate, while androgens, estrogens, corticosteroids, p-nitrophenol and DOPA
      did not serve as substrates. Apparent Michaelis constants for the 3beta
      hydroxysteroid substrates ranged from 0.6 to 8 microM.

PMID- 11527220
TI  - Repeated exposures of human skin equivalent to low doses of ultraviolet-B
      radiation lead to changes in cellular functions and accumulation of cyclobutane
      pyrimidine dimers.
AB  - Chronic exposure to sunlight may induce skin damage such as photoaging and
      photocarcinogenesis. These harmful effects are mostly caused by ultraviolet-B
      (UVB) rays. Yet, less is known about the contribution of low UVB doses to skin
      damage. The aim of this study was to determine the tissue changes induced by
      repeated exposure to a suberythemal dose of UVB radiation. Human keratinocytes in
      monolayer cultures and in skin equivalent were irradiated daily with 8 mJ/cm2 of
      UVB. Then structural, ultrastructural, and biochemical alterations were
      evaluated. The results show that exposure to UVB led to a generalized
      destabilization of the epidermis structure. In irradiated skin equivalents,
      keratinocytes displayed differentiated morphology and a reduced capacity to
      proliferate. Ultrastructural analysis revealed, not only unusual aggregation of
      intermediate filaments, but also disorganized desmosomes and larger mitochondria
      in basal cells. UVB irradiation also induced the secretion of metalloproteinase
      9, which may be responsible for degradation of type IV collagen at the basement
      membrane. DNA damage analysis showed that both single and repeated exposure to
      UVB led to formation of (6-4) photoproducts and cyclobutane pyrimidine dimers.
      Although the (6-4) photoproducts were repaired within 24 h after irradiation,
      cyclobutane pyrimidine dimers accumulated over the course of the experiment.
      These studies demonstrate that, even at a suberythemal dose, repeated exposure to
      UVB causes significant functional and molecular damage to keratinocytes, which
      might eventually predispose to skin cancer.

PMID- 11527221
TI  - Contribution of leucine 85 to the structure and function of Saccharomyces
      cerevisiae iso-1 cytochrome c.
AB  - Cytochrome c is a small electron-transport protein whose major role is to
      transfer electrons between complex III (cytochrome reductase) and complex IV
      (cytochrome c oxidase) in the inner mitochondrial membrane of eukaryotes.
      Cytochrome c is used as a model for the examination of protein folding and
      structure and for the study of biological electron-transport processes. Amongst
      96 cytochrome c sequences, residue 85 is generally conserved as either isoleucine
      or leucine. Spatially, the side chain is associated closely with that of the
      invariant residue Phe82, and this interaction may be important for optimal
      cytochrome c activity. The functional role of residue 85 has been examined using
      six site-directed mutants of Saccharomyces cerevisiae iso-1 cytochrome c,
      including, for the first time, kinetic data for electron transfer with the
      principle physiological partners. Results indicate two likely roles for the
      residue: first, heme crevice resistance to ligand exchange, sensitive to both the
      hydrophobicity and volume of the side chain; second, modulation of electron
      transport activity through maintenance of the hydrophobic character of the
      protein in the vicinity of Phe82 and the exposed heme edge, and possibly of the
      ability of this region to facilitate redox-linked conformational change.

PMID- 11527222
TI  - Induction of apoptosis in HT29 human intestinal epithelial cells by the cytotoxic
      enterotoxin of Aeromonas hydrophila.
AB  - The cytotoxic enterotoxin produced by Aeromonas hydrophila is considered to be
      the main virulence factor in gastrointestinal infections mediated by this
      pathogen. In this study, we examined the morphological and apoptotic effects of
      this toxin on HT29 cells, using light and electron microscopy in situ, as well as
      agarose gel electrophoresis of cell DNA. Cells treated with the cytotoxic
      enterotoxin became round and lost their polarity as well as their adhesion to
      each other and to the substrate. Cytoplasmic blebbing and nuclear condensation
      also occurred. DNA fragmentation was detected by TUNEL labelling and agarose gel
      electrophoresis. These results show that the cytotoxic enterotoxin of A.
      hydrophila can induce apoptosis in human intestinal cells in culture.

PMID- 11527223
TI  - Organophosphate food residues: a potential hazard (commentary).

PMID- 11527224
TI  - Food poisoning due to methamidophos-contaminated vegetables.
AB  - BACKGROUND: Organophosphate poisoning is well known for its characteristic
      symptoms and signs, but food poisoning caused by pesticide-contaminated food is
      seldom reported. CASE REPORT: We report three incidents of food poisoning that
      resulted from exposure to the organophosphate insecticide methamidophos in
      vegetables. These outbreaks caused a cholinergic syndrome in 4 patients. The
      cholinergic overactivity led as to suspect organophosphate food poisoning. All
      patients recovered well following appropriate therapy. The clinical diagnosis of
      organophosphate poisoning was confirmed by reduced levels of erythrocytes and
      plasma cholinesterase and the presence of methamidophos in the vegetable
      leftovers. The implicated vegetables and levels of methamidophos were: Ipomoea
      batatas 255 ppm, Gynura bicolor 110 ppm, and red cabbage 26.3 ppm. Since
      methamidophos is normally applied to vegetables during planting, improper
      selection and/or overuse of pesticide or improper harvest times may explain the
      occurrence of these high residue levels of methamidophos.

PMID- 11527225
TI  - Vegetable-borne methamidophos poisoning.

PMID- 11527227
TI  - Food-borne clenbuterol may have potential for cardiovascular effects with chronic
      exposure (commentary).

PMID- 11527226
TI  - Clenbuterol ingestion causing prolonged tachycardia, hypokalemia, and
      hypophosphatemia with confirmation by quantitative levels.
AB  - BACKGROUND: Clenbuterol is a long acting beta2-adrenergic agonist used in the
      treatment of pulmonary disorders. Acute clenbuterol toxicity resembles that of
      other beta2-adrenergic agonists. Most previously reported cases of clenbuterol
      toxicity describe patients who ate livestock illicitly treated with clenbuterol.
      CASE REPORT: We report a case of human clenbuterol toxicity confirmed and
      correlated with qualitative and quantitative serum clenbuterol assays. This
      poisoned patient, a 28-year-old woman, developed sustained sinus tachycardia at
      140/min, hypokalemia (2.4 mEq/L, 2.4 mmol/L), hypophosphatemia (0.9 mg/dL, 0.29
      mmol/L), and hypomagnesemia (1.52 mg/dL, 0.76 mmol/L) after ingesting a
      reportedly small quantity of clenbuterol. The patient received repeated doses of
      metoprolol to treat her cardiovascular stimulation and potassium chloride to
      treat her hypokalemia. She remained symptomatic for more than 20 hours after the
      ingestion. Analysis by enzyme-linked immunosorbent assay and liquid
      chromatography/mass spectrometry revealed a serum clenbuterol concentration of
      2.93 mcg/L 3 hours after the ingestion and an undetectable serum concentration 20
      hours after ingestion. It is noteworthy that at a serum concentration below the
      limit of detection by liquid chromatography/mass spectrometry, the patient
      remained symptomatic. Acute clenbuterol toxicity is rarely reported following
      illicit use in humans, and this is the first such case to provide confirmatory
      toxicological analysis.

PMID- 11527228
TI  - Calcium neutralizes fluoride bioavailability in a lethal model of fluoride
      poisoning.
AB  - OBJECTIVES: Acute systemic fluoride poisoning can result in systemic
      hypocalcemia, cardiac dysrhythmias, and cardiovascular collapse. Topical and
      intraarterial therapy with calcium or magnesium salts reduces dermal injury from
      fluoride burns. The mechanism of these therapies is to bind and inactivate the
      fluoride ion. The purpose of this study is to evaluate the effect of calcium and
      magnesium to decrease the bioavailability of fluoride in a lethal model of
      fluoride poisoning. METHODS: In preliminary studies, we determined that fluoride
      3.6 mM/kg intraperitoneally in the form of sodium fluoride was uniformly and
      rapidly fatal in a mouse model. Using this fluoride dose, we performed a
      controlled, randomized, blinded study of low- and high-dose calcium chloride (1.8
      and 3.6 mM/kg intraperitoneally, respectively) and magnesium sulfate (3.6 mM/kg
      intraperitoneally) to decrease the bioavailability of the fluoride ion. After
      injection with sodium fluoride, animals were immediately treated with injections
      of sodium chloride (control), calcium chloride (low- or high-dose), or magnesium
      sulfate. The major outcome was 6-hour survival using a Cox Proportional Hazard
      model. RESULTS: All untreated animals died within 60 minutes. Using a Cox
      Proportional Hazard model, each 1.8 mM/kg dose of calcium chloride administered
      reduced the risk of death by 33%. Magnesium sulfate treatment was not associated
      with a hazard reduction. CONCLUSION: Calcium chloride administered simultaneously
      with sodium fluoride reduces the bioavailability of fluoride poisoning in a mouse
      model. The equivalent dose of magnesium sulfate does not significantly decrease
      fluoride bioavailability.

PMID- 11527229
TI  - Acute toxicities of betel nut: rare but probably overlooked events.
AB  - BACKGROUND: Betel nut chewing has long been a social habit in Taiwan and other
      Asian and tropical countries. It produces various autonomic and psychoneurologic
      effects including tachycardia, flushing, warmth, cholinergic activation,
      alertness, and euphoria. Although the oral carcinogenic effects are well known,
      data concerning its acute toxicity are few. To better understand the toxicity of
      betel nut, cases reported to the Taiwan Poison Control Center as probable or
      possible betel nut-related toxicity (January 1988-June 1998) were reviewed. In
      the 17 cases suitable for review (14 males, 3 females, age 21 to 60 years), the
      most common manifestations were tachycardia/palpitations (7); tachypnea/dyspnea
      (6); hypotension and sweating (5); vomiting, dizziness, and chest discomfort (4);
      abdominal colic, nausea, numbness, and coma (3); and acute myocardial infarction
      and related manifestations (2). The reported quantity of betel nut used was low
      (1 to 6 nuts), except an extract of 100 betel nuts was used in 1 case and 66
      chewed in another. Most cases recovered within 24 hours after the exposure. One
      patient developed probable acute myocardial infarction and ventricular
      fibrillation and died despite repeated cardiac defibrillation. Although betel nut
      chewing is widespread, significant toxicity as reported to a poison center is
      rare. Because most betel nut-related effects are transient and mild in nature,
      the incidence of such events is likely to be underreported. Nevertheless, betel
      nut chewing can produce significant cholinergic, neurological, cardiovascular,
      and gastrointestinal manifestations. It is possible that it may aggravate cardiac
      diseases in susceptible patients but this hypothesis must be further
      investigated. Treatment is symptomatic. With timely support, rapid and complete
      recovery is anticipated but a small risk of major complications cannot yet be
      discounted.

PMID- 11527230
TI  - Use of hair analysis for confirmation of self-reported cocaine use in users with
      negative urine tests.
AB  - INTRODUCTION: Identification of cocaine use based on a urine test may miss many
      cases because of the short elimination half-life of the drug. Our objective was
      to verify the sensitivity of the cocaine hair test in admitted users. PATIENTS
      AND METHODS: Admitted cocaine users (38), that were 18-70 years of age and
      reported to have refrained from using cocaine in the few days to months prior to
      the test, were compared to 10 controls who claimed never to have used cocaine.
      All had negative urine tests for cocaine and benzoylecgonine by thin-layer
      chromatography. Cocaine and benzoylecgonine were extracted from unwashed hair and
      tested by established immunoassays. RESULTS: The hair test was positive in 37/38
      cases (97%) and in none of the controls. There was significantly more cocaine in
      black hair than in brown or blonde hair per mg of cocaine dose reported to have
      been consumed, highlighting a potential bias when interpreting test results in
      individuals with dark hair. There was a statistically significant correlation
      between reported dose used and hair concentrations of cocaine. DISCUSSION: The
      cocaine hair test appears to be highly sensitive and specific in identifying past
      cocaine use in the setting of a negative urine test.

PMID- 11527231
TI  - Age-specific and age-adjusted penetrance as poison center outcome measures.
AB  - BACKGROUND: The American Association of Poison Control Centers defines penetrance
      as the number of exposures per 1000 residents of a population during one year.
      This metric fails to account for confounding by age group variability. We
      demonstrate the error caused by using raw penetrance and present two alternate
      methods of calculation, age-specific penetrance and age-adjusted penetrance.
      METHODS: Data from the toxic exposure surveillance system were collected from
      calls to our 41 county regional poison centers in 1998. Age-specific penetrance
      (ASP) was calculated by dividing the number of exposures (E) in age interval "i"
      in county "A" by 1000 population in age interval "Pi" in county "A" or ASP =
      Ei/Pi. AAP is the summation of the weighted age-specific penetrance. Weights
      (w(si)) represent the relative age distribution of a standard population, in this
      case the 1998 US population. AAP = sigma(i) w(si) * Ei/Pi. RESULTS: [table: see
      text] County C has low raw penetrance and is known to have relatively fewer
      toddlers and presumably a lower incidence of poisoning. This demonstrates that
      raw penetrance misrepresents populations with small proportions of children and
      should not be used to compare promotion or prevention activities between
      populations. CONCLUSION: We recommend poison centers and the American Association
      of Poison Control Centers replace raw penetrance with age-adjusted penetrance as
      one measure of the effectiveness of a poison center's awareness efforts.

PMID- 11527232
TI  - Etiologic and demographic characteristics of poisoning: a prospective hospital
      based study in Oman.
AB  - BACKGROUND: The health care system in Oman is characterized by its rapid
      development and free medical services for all its nationals although traditional
      medicine still plays a major role in daily life. Epidemiological data on
      poisoning are scanty. OBJECTIVE: To determine the annual rate of poisoning
      related Accident & Emergency Department visits at Sultan Qaboos University
      Hospital in Oman and to evaluate, in both children and adults, the etiologic and
      demographic characteristics of poisoning cases. The poisoning pattern is
      contrasted to that of other countries. METHODS: A prospective observational study
      included all symptomatic and asymptomatic poisoning-related Accident & Emergency
      Department visits over 4 years (1996-1999). Data were recorded on a specifically
      designed poison reporting form. RESULTS: Two hundred and four poisoning-related
      Accident & Emergency Department visits were recorded corresponding to an average
      annual rate of 1.8/1000 Accident & Emergency Department visits. Therapeutic
      agents were most commonly involved (50% of all cases). Accidental poisoning in
      toddlers was most commonly caused by drugs. Intentional poisoning in adults
      involved mainly therapeutic agents (50%), particularly analgesics, followed by
      industrial and environmental agents (25%). Animal poisoning (14%) was most
      commonly encountered in adult males. Traditional remedies constituted 7% of all
      poisoning cases. A total of 148 patients (73%) were admitted for 1 to 175 days.
      CONCLUSIONS: Compared to studies performed in urban hospitals in other countries,
      (1) the annual rate of poisoning-related Accident & Emergency Department visits
      was substantially lower, (2) psychoactive drugs were less frequently incriminated
      in intentional ingestions, and (3) we found a significantly higher frequency of
      poisoning by animals and traditional remedies than reported by urban hospitals in
      other Middle Eastern countries. The limitations of our study (Accident &
      Emergency Department-based data collection in an urban hospital) do not permit
      extrapolation to the rest of the country.

PMID- 11527233
TI  - The effects of lithium, valproic acid, and carbamazepine during pregnancy and
      lactation.
AB  - The chronic, complex, and episodic course of bipolar mood disorder presents a
      particularly formidable challenge to the clinician making a treatment plan for
      the onset or recurrence of the illness during pregnancy and lactation. Women
      treated with anti-manic drugs who become pregnant are commonly considered to be
      at high risk for fetal complications during the pregnancy or during lactation.
      The risks of antimanic drug use during pregnancy include teratogenic effects,
      direct neonatal toxicity, and the potential for longer-term neurobehavioral
      sequela. The use of medications during pregnancy and lactation requires critical
      attention to the timing of exposure, dosage, duration of use, and fetal
      susceptibility. The postnatal period is a time of increased onset and relapse of
      mental illness. No antimanic drug can be proven completely safe. Prescribing
      antimanic medications with a long safety record, avoiding exposure in the first
      trimester; avoiding multidrug regimens, and prescribing the lowest dose for the
      shortest duration will minimize the fetal risk. This review considers treatment
      with lithium, valproic acid, and carbamazepine. It assesses the risk to the
      fetus, the perinatal risks for the infant, the risks associated with treatment
      during the puerperium and breast-feeding, and the risks to the later development
      of the child.

PMID- 11527234
TI  - Efficacy of continuous venovenous hemodialysis in the treatment of severe lithium
      toxicity.
AB  - The syndrome of lithium toxicity has been well described. Hemodialysis is the
      recommended treatment for severe toxicity. We report a case in which continuous
      venovenous hemodialysis was used in the treatment of lithium toxicity. The
      calculated average lithium clearance was 23 mL per minute, comparing favorably
      with that of normal renal clearance (20-30 mL/min) and of intermittent
      hemodialysis (50-100 mL/min). This report discusses the potential benefits of
      this therapy in a hemodynamically unstable patient who may not tolerate
      hemodialysis.

PMID- 11527235
TI  - Abuse of telazol: an animal tranquilizer.
AB  - BACKGROUND: Telazol (tiletamine hydrochloride 50 mg/mL, zolazepam hydrochloride
      50 mg/mL) is utilized in veterinary medicine as a small-animal anesthetic.
      Telazol is comparable to ketamine in efficacy, and in conjunction with ketamine,
      has been responsible for one reported human fatality. We report a case of a woman
      who abused telazol. CASE REPORT: A 30-year-old female employee at a local zoo was
      found unresponsive by fellow workers in a clean animal treatment room. Initial
      reports were that she had injected veterinary-grade diazepam and telazol. On
      scene paramedics reported her as obtunded and arousable to deep painful stimuli,
      with gag reflex intact. Systolic blood pressure was 90 mm Hg by palpation. A
      fresh needle puncture mark was present on her right arm; nearby were a syringe,
      tourniquet, and bottles of each drug. Emergency Department assessment included
      airway, breathing, circulation, and intravenous access. She was lavaged and given
      activated charcoal with a cathartic. Shortly after arrival, she became alert and
      oriented. Family members insisted this was not an overdose. The patient had been
      previously evaluated for reported episodes of syncope, "only in the evening,
      while at work," and was prescribed diazepam for anxiety. Product information on
      telazol was limited to the Veterinary Drug Physician's Desk Reference. A urine
      drugs-of-abuse screen was positive for benzodiazepines and cannabinoids. The
      patient subsequently revealed a history of recreational use of telazol. She was
      discharged to an in-patient detoxification facility, 12 hours postadmission.
      CONCLUSION: Telazol used in veterinary medicine as an anesthetic agent, is
      structurally related to ketamine. Telazol causes almost immediate anesthetic
      effects, and sudden alertness is not uncommon as the effects of the drug subside.
      Urine drugs-of-abuse screens are unlikely to identify telazol. We report a
      veterinary worker who abused telazol.

PMID- 11527236
TI  - Erythromelalgia and mushroom poisoning.
AB  - OBJECTIVE: To report the first European observations of erythromelalgia due to
      mushroom poisoning. METHODS: Clinical features of erythromelalgia were observed
      in 7 cases seen over 3 years. All patients had eaten the same mushrooms species,
      gathered in the same French alpine valley. Erythromelalgia was first described in
      Japan after Clitocybe acromelalga ingestion. Clitocybe amoenolens was identified
      as the possible cause of poisoning in our cases.

PMID- 11527237
TI  - Self-poisoning with Colchicum autumnale L. flowers.
AB  - A 44-year-old man ingested about 40 flowers of Colchicum autumnale L. The patient
      presented with nausea, vomiting, and abdominal pain 2 hours after ingestion and
      had diarrhea 14 hours after ingestion. Hematological values remained within
      normal range. Treatment was mainly supportive. The outcome was favorable. The
      intoxication was confirmed by high-performance liquid chromatography-mass
      spectrometry. Maximal colchicine levels were 4.34 ng/mL at 13 hours in plasma and
      5.43 ng/mL at 16 hours in erythrocytes. CONCLUSION: We report one of the few
      symptomatic cases of Colchicum autumnale L. poisoning confirmed by toxicological
      analysis.

PMID- 11527238
TI  - Amatoxin poisoning from ingestion of Japanese Galerina mushrooms.
AB  - BACKGROUND: Although some Japanese Galerina species poisonings manifest as
      gastrointestinal symptoms followed by late-onset hepatorenal failure (phalloides
      syndrome), the toxin responsible for this has not been determined. CASE REPORT:
      We report a 6-year-old boy who developed characteristic cholera-like diarrhea and
      late-onset severe hepatic deterioration after eating mushrooms, later identified
      as a Galerina species, most likely Galerina fasciculata. A residual mushroom
      revealed alpha-amanitin. This account is the first known reported case of
      poisoning by Japanese Galerina species where an amatoxin was demonstrated to be
      responsible for the toxicity.

PMID- 11527239
TI  - The effect of gamma hydroxybutyrate on serum osmolality.

PMID- 11527240
TI  - A unique valproic acid ingestion.

PMID- 11527241
TI  - Sildenafil overdose in a female patient.

PMID- 11527242
TI  - The rising prevalence of asthma in young Melbourne adults is associated with
      improvement in treatment.
AB  - BACKGROUND: Asthma is a common source of morbidity and is now recognized as a
      national health priority in Australia. Although a number of epidemiologic studies
      have been conducted in Australia to determine the prevalence of asthma in adults,
      it is unclear whether the prevalence is changing. OBJECTIVES: To determine the
      prevalence in 1998 of self-reported asthma and respiratory symptoms among young
      adults and changes in prevalence between 1990 and 1999. METHODS: Cross-sectional
      postal survey to 4,455 young adults (aged 20 to 44 years) randomly selected from
      the electoral rolls of the inner southeastern suburbs of metropolitan Melbourne.
      The survey instrument was the validated European Community Respiratory Health
      Survey screening questionnaire, which gathered data on self-reported respiratory
      symptoms, including whether asthma had been diagnosed. Identically worded
      questions from similar surveys conducted in 1990, 1992, and 1999 were used to
      compare changes in prevalence. RESULTS: A response rate of 72% was achieved in
      1998 after three mailings and telephone followup. Forty-two percent reported
      nasal allergies, 26% wheezed within the past 12 months, and 20% ever had asthma.
      The prevalence of doctor-diagnosed asthma was 18%, whereas 10% reported using
      asthma medications within the past 12 months. Nine percent of respondents
      reported an asthma attack within the past 12 months. The prevalence of having
      ever had asthma, doctor-diagnosed asthma, and using asthma medications had
      increased significantly since 1990. However, the prevalence of respiratory
      symptoms did not significantly change over this time. CONCLUSIONS: The prevalence
      of asthma is likely to be rising, but the symptoms of asthma are being better
      managed in young Melbourne adults.

PMID- 11527243
TI  - Asthma mortality in Uruguay, 1984-1998.
AB  - BACKGROUND: Asthma mortality rates have increased worldwide during the past
      several years despite the increased availability of new and effective
      medications. Few studies show reliable data from Latin American countries.
      OBJECTIVE: To determine asthma mortality rates from 1984 to 1998 and to relate
      mortality to sales of asthma medications. METHODS: We conducted a retrospective
      epidemiologic study in the total population of Uruguay. Data were obtained from
      the Department of Statistics of the Ministry of Public Health. Trends in
      mortality rates were analyzed using linear regression procedures. Spearman rank
      correlations were used to relate mortality rates to sales of asthma medications.
      RESULTS: The mean overall mortality rate was 5.10 per 100,000 during the period
      1984 to 1998, (range 6.08 to 3.39) and showed a decreasing trend (P = 0.001).
      During the period 1995 to 1998, a more pronounced decrease was observed (mean
      mortality rate, 4.10 per 100,000). In the 5- to 34-year-old age group the mean
      mortality rate was 0.43 (range 0.65 to 0.13). Similarly, the mortality rate in
      this age group decreased particularly in the 1994 to 1998 period (mean 0.19; P =
      0.005). Finally, the mortality rate was inversely correlated with sales of
      inhaled corticosteroids; for the overall mortality rate, p = -0.71, P = 0.003;
      for 5- to 34-year-old age group, p = -0.63, P = 0.01. CONCLUSIONS: Although
      mortality attributable to asthma seems to be decreasing, the overall mortality
      rate is still high compared with more economically developed countries. A more
      pronounced decrease in asthma mortality has been seen in the 5- to 34-year-old
      group. At present, Uruguay is a Latin American country with a low rate of asthma
      mortality. This is probably related to the use of new therapies to treat asthma.

PMID- 11527244
TI  - Prevalence of mood disorders and relationship to asthma severity in patients at
      an inner-city asthma clinic.
AB  - BACKGROUND: Depressive symptoms are associated with noncompliance and even sudden
      death in asthma patients. Some studies suggest that low-income, minority, inner
      city asthma patients may be at high risk for asthma-related morbidity and
      mortality in which depression may be a risk factor. Minimal data are available on
      the prevalence of depression and other mood disorders in asthma patients.
      OBJECTIVE: In this pilot study, we examined the prevalence of depression and the
      association between depression and measures of asthma severity in patients at an
      inner-city asthma clinic. METHODS: Mood disorders were diagnosed using a
      diagnostic interview given to patients (N = 44) at asthma clinic visits. Inhaled
      steroid dose, FEV1 percentage, and asthma severity were also obtained. RESULTS:
      Eighteen patients (41%) had a lifetime mood disorder but only seven of these
      patients received pharmacotherapy. Patients with a past mood disorder had
      significantly higher FEV1 percentage predicted values (P = 0.03) than those
      without a mood disorder. Trends toward less severe asthma (P = 0.13) and lower
      inhaled steroid dose (P = 0.13) in patients with a mood disorder history were
      also found. CONCLUSIONS: The data suggest that mood disorders are common, but
      often unrecognized and untreated in asthma patients. The data also suggest that
      mood disorders are not necessarily associated with more severe asthma, at least
      in the population studied.

PMID- 11527245
TI  - Case report of venom immunotherapy for a patient with large local reactions.
AB  - BACKGROUND: Inadvertent Hymenoptera stings reportedly elicit large local
      reactions in up to 17% of the general population. Current practice parameters do
      not recommend venom immunotherapy (IT) for these cases. OBJECTIVE: The goal of
      this case study was to investigate the clinical and immunologic consequences of
      venom IT in a newly sensitized individual with large local reactions using an
      intentional sting challenge before and after treatment to document changes in
      reaction severity. METHODS: A 47-year-old man became honeybee venom (HBV)
      allergic with progressively larger reactions at honeybee sting sites with
      subsequent stings. Then, a sting on his forefinger produced a large (62 cm) local
      reaction with swelling throughout the arm that persisted for more than 4 weeks
      with severe pain. He refused steroid therapy and voluntarily requested venom IT
      with honeybee-sting challenges to monitor clinical parameters and immunologic
      changes in his skin and serum before and 7 months post-HBV maintenance IT.
      RESULTS: A single pre-IT bee sting challenge produced an 11.4-cm wheal with 13-cm
      erythema at the sting site after 15 minutes, followed by several weeks of edema
      that involved the entire arm. After rapid escalation of venom IT to maintenance
      in 7 weeks, a post-maintenance IT sting challenge with two honeybees produced a 3
      cm diameter erythema with no wheal at 15 minutes and no late-phase induration.
      Complete loss of any visible reaction at the field sting site resulted after 13
      months of maintenance venom IT. A HBV-specific IgG antibody level >3.5 microg/mL
      and IgG/IgE antibody molar ratio >500 persisted over the period of venom IT, with
      venom skin reactivity diminishing 100-fold. CONCLUSIONS: These results support
      venom IT use in the treatment of Hymenoptera venom-sensitive individuals who
      experience large local reactions and are at risk for repetitive inadvertent
      stings.

PMID- 11527246
TI  - Hereditary angioedema first apparent in the ninth decade during treatment with
      ACE inhibitor.
AB  - BACKGROUND: Hereditary angioedema ordinarily manifests itself in childhood. The
      development of angioedema in this disease and as a side effect of angiotensin
      converting enzyme inhibitor treatment is caused by similar mechanisms. METHODS:
      We report a case of female patient, diagnosed with hereditary angioedema at age
      90, who experienced the first attack 8 years earlier during angiotensin
      converting enzyme inhibitor use. CONCLUSIONS: This patient presented with her
      first episode of hereditary angioedema at the oldest age ever reported. A careful
      family history, especially for angioedema, should be taken in patients of all
      ages before initiating treatment with angiotensin-converting enzyme inhibitor.

PMID- 11527247
TI  - Chickpea: a major food allergen in the Indian subcontinent and its clinical and
      immunochemical correlation.
AB  - BACKGROUND: The food allergy pattern of a country is influenced by the foods most
      commonly consumed. In India, the majority of the population consumes a vegetarian
      diet made up of pulse (legumes), cereals, and vegetables. In contrast to many
      western countries, chickpea preparations are consumed in large quantities in
      India. This study reports for the first time chickpea hypersensitivity reactions
      diagnosed with in vivo and in vitro tests. METHODS: One thousand four hundred
      patients visiting allergy clinics were randomly selected for the study. Those
      patients reporting an allergic reaction on every occasion after eating chickpea
      were considered history-positive. Modified prick tests were performed with
      chickpea and other members of the legume family on all these patients. The claims
      of the history-positive patients were verified with double-blind, placebo
      controlled food challenges (DBPCFCs). Proteins in chickpea extracts were
      separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and
      transferred on nitrocellulose paper. Serum specimens from history-positive
      patients were analyzed by immunoblot and ELISA. To verify the IgE specificity, an
      immunoblot inhibition assay was also performed. RESULTS: Of the 1,400 patients
      screened, 142 patients were history-positive to some food and 59 of these
      implicated chickpeas. Forty-one patients were skin test-positive and 31 were
      DBPCFC-positive for chickpea. The predominant symptoms after chickpea ingestion
      were respiratory. The ELISA results did not correlate well with the DBPCFC
      results; however, the skin test results correlated with DBPCFC in 75% of
      patients. Immunoblot analysis showed that 70, 64, 35, and 26 kD proteins were
      major allergens. CONCLUSIONS: Chickpea is an important source of allergen that
      can cause IgE-mediated hypersensitivity reactions ranging from rhinitis to
      anaphylaxis.

PMID- 11527248
TI  - Cromolyn sodium suppresses eosinophilic inflammation in patients with aspirin
      intolerant asthma.
AB  - BACKGROUND: Although administration of cromolyn sodium is one of the most useful
      drugs for the treatment of aspirin-intolerant asthma (AIA), both its
      pharmacologic mechanism of action and association with the pathogenesis remain
      obscure. OBJECTIVE: This study was designed to investigate the protective effect
      of cromolyn sodium on airway responsiveness to the sulpyrine provocation test,
      and to examine whether its activity is associated with a reduction in
      eosinophilic inflammation. METHODS: Patients were randomly assigned to receive
      cromolyn sodium (20 mg/2 mL, or 1 ampoule; Fujisawa, Osaka, Japan) or matching
      placebo (2 mL of saline) four times daily for 1 week. We evaluated the effects of
      pretreatment with cromolyn sodium on bronchoconstriction precipitated by
      inhalation of sulpyrine in 16 adult patients with mild or moderate AIA; those who
      were in stable clinical condition were allocated to this study. A double-blind,
      randomized, crossover design was used. Blood and sputum samples were taken in the
      morning on the sulpyrine provocation testing day. Eosinophil counting and
      measurement of eosinophilic cationic protein (ECP) were performed. RESULTS:
      Inhaled cromolyn sodium protect against aspirin-induced attacks of asthma through
      mechanisms not related to the bronchodilator property, but related to the
      improvement of the bronchial hypersensitivity, almost completely in all patients
      (P < 0.001). After 1 week's treatment with cromolyn sodium, patients' symptoms,
      blood and sputum eosinophils counts, and sputum ECP levels were significantly
      decreased compared with both placebo and baseline. CONCLUSIONS: Cromolyn sodium
      has a bronchial anti-inflammatory effect associated with decreased eosinophilic
      infiltration. This is the first report that cromolyn sodium reduces blood and
      sputum eosinophils counts and sputum ECP levels in AIA.

PMID- 11527249
TI  - Psocoptera spp. (book louse): a new major household allergen in Mumbai.
AB  - BACKGROUND: Exposure and sensitization to indoor allergens of house dust mites
      and insects is well established. However, there are no reports on the
      allergenicity of Psocoptera spp. (book louse). These insects are known to inhabit
      various terrestrial habitats such as tree bark (bark lice), old papers, books,
      stored food products, etc and gain entry into human dwellings through these
      modes. They have the potential to sensitize individuals with an occupational
      exposure to them. OBJECTIVE: Our objective is to use clinical and immunologic
      techniques to evaluate the extent of sensitization to Psocoptera in patients with
      nasobronchial allergy. We also have the objective to determine the extent of
      Psocoptera infestation in houses in Mumbai (Bombay). METHODS: An entomologic
      analysis of dust samples in houses in Mumbai was carried out and Psocoptera found
      in these samples was mass-cultured. Two hundred patients were checked for allergy
      to the Psocoptera extracts using skin test. Total IgE and specific IgE to
      Psocoptera in sera from Psocopotera-sensitive patients' sera were estimated by
      enzyme immunoassay. IgE-binding proteins of Psocoptera were determined by
      immunoblotting experiments. RESULTS: Among the 75 house dust samples from Mumbai
      analyzed for the presence of Psocoptera, 25% were found to be infested by
      Psocoptera. Strong skin sensitivity to Psocoptera was found in 20% of patients.
      Total IgE levels >150 IU/mL were found in these patients and high levels of
      specific IgE to Psocoptera were detected by ELISA. Immunoblot analysis revealed
      67, 59, 43, and 27 kD proteins as major allergens of Psocoptera. CONCLUSIONS:
      Psocoptera is an important allergen in Mumbai as it causes IgE mediated responses
      in 20% of the allergic population studied.

PMID- 11527250
TI  - Effects of pranlukast, a cysteinyl leukotriene receptor 1 antagonist, combined
      with inhaled beclomethasone in patients with moderate or severe asthma.
AB  - BACKGROUND: Although inhaled steroids are used as the first line of therapy in
      asthmatic patients, symptoms of asthma do not improve completely in some
      patients. OBJECTIVE: To investigate the effects of pranlukast, a cysteinyl
      leukotriene receptor 1 antagonist, in patients with moderate/severe asthma, when
      combined with beclomethasone dipropionate (BDP). METHODS: Protocol 1: After a 2
      week observation period, 41 patients with moderate asthma were divided into those
      receiving BDP at 1,600 microg/day or 800 microg/day + pranlukast (450 mg/day).
      The effect of treatment was evaluated by measuring AM peak expiratory flow rate,
      symptom score, frequency of beta2-agonists, and daily variability of peak
      expiratory flow rate. Protocol 2: 39 patients participated in this study
      including those with moderate asthma on 800 microg/day BDP (group I), severe
      asthma on BDP at 1,600 microg/day (group II), and severe asthma on 1,600
      microg/day BDP + 5 to 20 mg prednisolone (group III). Patients of all groups were
      additionally treated with pranlukast. RESULTS: Protocol 1: Both treatment
      regimens resulted in improvement in each clinical parameter. There were no
      significant differences in the effects of two treatment regimens. Protocol 2:
      Pranlukast was effective in group I and II, but not in group III. In groups I and
      II, pranlukast tended to be more effective when BDP was introduced within the
      first year of onset of asthma. CONCLUSIONS: Pranlukast is effective for patients
      with moderate asthma and those patients with severe asthma who are not treated
      with oral steroids. Pranlukast is more effective in patients treated with BDP
      early after onset.

PMID- 11527251
TI  - Zileuton and atopic dermatitis.

PMID- 11527252
TI  - Prevalence of latex allergy.

PMID- 11527253
TI  - Is there hope in studies demonstrating an increase in asthma prevalence?

PMID- 11527254
TI  - 2001: the asthma odyssey.

PMID- 11527255
TI  - Understanding the pathogenesis of allergic asthma using mouse models.
AB  - OBJECTIVE: This paper reviews the current views of the pathogenesis of airway
      eosinophilic inflammation and airway hyperresponsiveness (AHR) in allergic asthma
      based on mouse models of the disease. The reader will also encounter new
      treatment strategies that have arisen as this knowledge is applied in practice.
      DATA SOURCES: MEDLINE searches were conducted with key words asthma, mouse model,
      and murine. Additional articles were identified from references in articles and
      book chapters. STUDY SELECTION: Original research papers and review articles from
      peer-reviewed journals were chosen. RESULTS: Although the mouse model does not
      replicate human asthma exactly, the lessons learned about the pathogenesis of
      allergic airway inflammation and AHR are generally applicable in humans. Type 2 T
      helper lymphocytes (Th2) orchestrate the inflammation and are crucial for the
      development of AHR. Cells and molecules involved in T cell activation (dendritic
      cells, T cell receptor, major histocompatibility complex molecule, and
      costimulatory molecules) are also vital. Besides these, no other cell or molecule
      could be shown to be indispensable for the establishment of the model under all
      experimental conditions. There are at least three pathways that lead to AHR. One
      is dependent on immunoglobulin E and mast cells, one on eosinophils and
      interleukin-5 (IL-5), and one on IL-13. Eosinophils are probably the most
      important effector cells of AHR. Radical methods to treat asthma have been tested
      in the animal model, including modifying the polarity of lymphocyte response and
      antagonizing IL-5. CONCLUSIONS: AHR, the hallmark of asthma, is attributable to
      airway inflammation ultimately mediated by helper T cells via three pathways, at
      least. The mouse model is also a valuable testing ground for new therapies of
      asthma.

PMID- 11527256
TI  - Pancreaticoenteric anastomotic leak following pancreaticoduodenectomy.

PMID- 11527257
TI  - Serious injuries from airbags.

PMID- 11527258
TI  - Colorectal anastomotic leak rates are measures of technical skill in surgery.

PMID- 11527259
TI  - Determinants of pancreaticoenteric anastomotic leak following
      pancreaticoduodenectomy.
AB  - BACKGROUND: The purpose of the present paper was to study the incidence,
      presentation and management of pancreaticoenteric anastomotic (PEA) leak
      following pancreaticoduodenectomy (PD) and to identify risk factors associated
      with PEA leak. METHODS: One hundred and twenty patients underwent PD for benign
      and malignant pancreatic and periampullary lesions from 1989 to 1998.
      Prospectively collected data were analysed for incidence and outcome of PEA leak.
      Four clinical, three laboratory parameters, preoperative biliary drainage (PBD),
      perioperative octreotide use, nine intraoperative parameters, site of tumour and
      stage of malignant tumours were analysed by univariate and multivariate logistic
      regression analysis to identify factors influencing PEA leak. RESULTS: Pancreatic
      leak developed in 15 (12.5%) patients. Nine patients (60%) had a PEA leak that
      manifested as controlled leak through the drain. All were managed conservatively
      and the leak stopped after a mean duration of 17 days (range: 6-32 days). Six
      (40%) patients had associated intra-abdominal complications, and three (50%) died
      in the postoperative period. Pancreatic fistula healed in the three remaining
      patients after a mean duration of 18 days (range: 15-25 days). Diabetes (P =
      0.02; odds ratio (OR) = 4.60; 95% confidence interval (CI): 1.23-17.18), PBD (P =
      0.03; OR = 4.82; 95% CI: 1.21-19.24), sequence of reconstruction (bilioenteric
      anastomosis as first anastomosis; P = 0.01; OR = 6.25; 95% CI: 1.45-26.83) and
      duration of surgery > 8 h (P = 0.01; OR: 5.61; 95% CI: 1.54-20.39) were
      associated with a significantly higher incidence of PEA leak. CONCLUSION:
      Pancreaticoenteric anastomotic leak occurred in 12% of patients undergoing PD for
      pancreatic and periampullary tumours. The majority of these were uncomplicated
      and healed with conservative treatment. Complicated leaks were associated with
      high mortality. Diabetes mellitus, PBD, prolonged surgery and the sequence of
      reconstruction were risk factors associated with an increased incidence of PEA
      leak.

PMID- 11527260
TI  - Anastomotic leak in colorectal surgery: a single surgeon's experience.
AB  - BACKGROUND: Anastomotic leakage following colorectal resection and anastomosis
      has been proposed as a colorectal surgical indicator. Leak rates after elective
      surgery vary and tend to be higher as anastomoses become lower. The present study
      audits leak rates and outcomes of patients undergoing colorectal surgery, under
      the care of a single surgeon, in two geographically different centres. METHODS:
      Patients presenting to the University Colorectal Service in Wellington between
      1975 and 1990 and patients presenting to the colorectal service at King Faisal
      Specialist Hospital (KFSH) between 1990 and 1999 were recorded in computerized
      databases. These databases were searched for patients who developed anastomotic
      leakage. The records of patients identified were examined in relation to
      diagnoses, presentation, primary operation, further surgery performed, and final
      outcome. RESULTS: Two thousand and 11 patients were entered into the Wellington
      database and 1,348 were entered into the Riyadh database. Twenty-nine patients
      with a leaking anastomosis (3.6%) were identified. There were 19 male patients.
      The postoperative mortality rate in patients who did not leak was 1.7% but in
      patients who developed a leak after the same operation this rate was 24.1%. Most
      patients who sustained a leak had an original diagnosis of colorectal cancer.
      More non-leaking anastomoses were sutured. Sixteen patients with leaks (55.2%)
      received perioperative total parenteral nutrition (TPN) (9.2% in the no-leak
      group). Leaking anastomoses were associated with more postoperative respiratory
      problems (55.2% vs 24.0%) and wound infections (65.5% vs 14.8%). Of the 22 living
      patients, seven had no surgical intervention, 14 had stomata (two stomata were
      retained) and one patient with a localized leak was drained percutaneously. Five
      other patients in addition to having a stoma constructed were drained
      percutaneously. No patient developed an enteric fistula following leakage.
      CONCLUSION: Anastomotic leakage may be minimized by ensuring that patients are as
      fit as possible prior to surgery, stomata are used liberally, particularly in
      emergency patients, and a good anastomotic technique is utilized at all times.
      Despite these precautions some patients will still develop a leak and if timely
      and appropriate action is taken the majority will survive and have their stomata
      closed.

PMID- 11527261
TI  - Diagnostic value of preoperative RT-PCR-based screening method to detect
      carcinoembryonic antigen-expressing free cancer cells in the peritoneal cavity
      from patients with gastric cancer.
AB  - BACKGROUND: At present the most reliable method for the diagnosis of peritoneal
      micrometastasis of gastric cancer is peritoneal wash cytology, but the
      sensitivity of this method is low. The aim of the present study was to verify
      whether carcinoembryonic antigen (CEA) reverse transcriptase-polymerase chain
      reaction (RT-PCR) assay can enhance the sensitivity and specificity of
      conventional cytology, and to determine how this technique can improve the
      accuracy of peritoneal recurrence. METHODS: The present study included 230
      patients with gastric cancer. Preoperative peritoneal wash was done by a
      paracentesis, followed by conventional cytology, CEA measurement, and CEA RT-PCR
      of recovered fluid. RESULTS: The CEA RT-PCR assay yielded 40 (17%) positives,
      which included none of the 26 patients with benign disease. The incidence of
      positive cytology and CEA level in wash fluid was 19% and 15%, respectively.
      Logistic stepwise regression analysis revealed that lymph node status, depth of
      invasion, venous invasion, and the results of peritoneal cytological examination,
      and CEA RT-PCR assay were independently related to peritoneal recurrence. The CEA
      level in the wash fluid was not related to peritoneal recurrence. Peritoneal
      cytological examination was the most significant predictive factor for peritoneal
      recurrence with a sensitivity of 46%, specificity of 94% and accuracy of 73%,
      while the corresponding values of the CEA RT-PCR assay were 31%, 95%, and 73%.
      Combining cytological examination with CEA RT-PCR assay resulted in a sensitivity
      rate for peritoneal recurrence of 57%, an 11% improvement over that of cytology
      alone. CONCLUSION: The data indicate that the use of a combination of CEA RT-PCR
      and cytological assay is more likely to identify patients who will develop
      peritoneal recurrence. This may be useful for the classification of patients for
      the most suitable therapeutic trials.

PMID- 11527262
TI  - Local resection of ampullary adenocarcinomas of the duodenum.
AB  - BACKGROUND: Pancreaticoduodenectomy (PD) is considered to be the optimal
      treatment for ampullary adenocarcinomas. Local resection (LR) is a less invasive
      and potentially equally effective alternative for cancers with favourable
      prognostic features. Identification of these prognostic parameters may allow
      selection of patients suitable for LR. METHODS: Twenty-five patients were treated
      for a primary Vater's ampulla adenocarcinoma at the Alfred Hospital, Melbourne,
      Australia, between January 1989 and January 2000. Risk factors for cancer
      recurrence were evaluated and the specific role of LR was defined. RESULTS:
      Fourteen patients had PD, five had LR and six had bypass procedures (five biliary
      stents; one operative bypass). Presenting symptoms included jaundice (64%),
      abdominal pain (54%) and weight loss (32%). Adenocarcinomas that were resected
      had a median diameter of 2.5 cm, and were limited to the ampulla in 26% (T1),
      invaded the duodenal wall in 42% (T2) and infiltrated 2 cm or less into the
      pancreas in 32% (T1) of cases. Locally resected cancers were confined to the
      ampulla or invaded the duodenum and recurred in one patient following excision.
      Six recurrences occurred in total, influenced significantly by T staging (P =
      0.009). Patient age, preoperative symptoms, laboratory tests, tumour size,
      differentiation, ulceration, lymphovascular spread and perineural invasion had no
      effect on recurrence. Patients undergoing LR had lower morbidity and mortality,
      reduced blood transfusion requirements and shorter hospital stay than those
      treated by PD. CONCLUSIONS: T staging predicts the risk of tumour recurrence and
      can be determined using endoscopic ultrasound. Local resection is a suitable
      alternative to pancreaticoduodenal resection in patients with T1 and T2
      adenocarcinomas with a maximum diameter of 3 cm or less.

PMID- 11527264
TI  - Use of a computer-controlled bipolar diathermy system in radical prostatectomies
      and other open urological surgery.
AB  - BACKGROUND: Ligasure is a computer-controlled bipolar diathermy system, designed
      to optimally seal vessels < or = 7 mm in diameter. The aim of the present study
      was to evaluate its application to open urological surgery. METHODS: The Ligasure
      device was used in 32 consecutive open surgical cases, including 25 radical
      prostatectomies, five radical nephrectomies, one partial nephrectomy and one
      nephro-ureterectomy. All procedures were performed using standard surgical
      techniques, with the exception that the Ligasure device was used for haemostasis.
      This included pelvic lymphatics and prostatic, adrenal, gonadal and aberrant
      obturator vessels, as well as vessels associated with the ureter, vasa, seminal
      vesicles, peri-renal fat, peritoneum and peri-adrenal tissues. Vessels > 7 mm in
      diameter, such as the renal artery, were ligated. In no patients were haemostatic
      clips used. RESULTS: In all procedures, vessels and other structures < 7 mm were
      successfully sealed using the Ligasure device. For some structures, such as the
      prostatic pedicles and the seminal vesicles, the Ligasure device was much easier
      to apply than haemostatic clips. Use of the Ligasure device reduced the operating
      time (mean: 113 min vs 135.5 min; P < 0.001) and blood loss (mean: 529 mL vs 642
      mL; P < 0.02) for radical prostatectomies. No intraoperative or postoperative
      blood transfusions were required. There were no postoperative haemorrhages, lymph
      leakage or lymphocoeles. Median inpatient hospital stay was 7 days (range: 6-9
      days) and no patients required readmission. CONCLUSION: The Ligasure, device was
      safe and easy to use in major urological procedures.

PMID- 11527263
TI  - Clinical value of magnetic resonance imaging of the knee.
AB  - BACKGROUND: Magnetic resonance (MR) imaging is an accurate imaging modality of
      the knee. The role of MR in clinical practice has not been precisely defined,
      largely due to the relative expense of the technique. METHODS: For each new
      patient with a knee problem who was referred for MR, a provisional diagnosis was
      made together with a level of certainty regarding the diagnosis. The waiting time
      for the scan was recorded. To assess clinical usefulness the MR diagnosis was
      compared with the provisional diagnosis and classified according to the following
      descending order of value: unexpected negative (no intra-articular pathology),
      confirmatory negative, unexpected positive or confirmatory positive. To assess
      accuracy of the MR diagnosis, the operative diagnosis was compared to the MR
      diagnosis in those patients who underwent arthroscopy. RESULTS: Fifty-two per
      cent of scans were assessed as being very useful and a further 20% were assessed
      as being moderately useful. Magnetic resonance had a 95% accuracy for medial
      meniscal tears, 91% accuracy for lateral meniscal tears, and 98% accuracy for
      anterior cruciate ligament tears, similar to previously reported studies. The
      diagnostic arthroscopy rate in the patients who underwent MR scanning was similar
      to that in patients for whom the surgeon was more confident about the diagnosis
      and who therefore did not undergo MR scanning. The diagnostic arthroscopy rate
      could have been reduced if surgery had not been performed in 14 patients who had
      a negative MR scan. CONCLUSIONS: There is a role for selective use of MR in the
      assessment of knee conditions. In particular, MR can be used to reduce the
      diagnostic arthroscopy rate.

PMID- 11527265
TI  - Treatment of childhood phimosis with a moderately potent topical steroid.
AB  - BACKGROUND: Recently, topical steroid application has been shown by a small
      number of studies to be an effective alternative to circumcision for the
      treatment of phimosis. However, only potent or very potent corticosteroids have
      been more thoroughly studied in this treatment option. A prospective study was
      conducted to determine whether comparable results could be achieved using a
      weaker steroid cream. METHODS: Boys, 3-13 years of age, with non-retractable
      foreskin due to a tight ring at the tip were offered the regimen of twice-daily
      preputial retraction and topical application of 0.02% triamcinolone acetonide
      cream. The degree of preputial retractability was assessed at presentation and at
      4 and 6 weeks of treatment. Success was defined as full retraction or free
      retraction up to agglutination of the foreskin to the glans. RESULTS: Eighty
      three boys completed the treatment. Successful retraction was achieved in 48/83
      (58%) patients after 4 weeks and 70/83 (84%) patients after 6 weeks of
      application. The overall response rate aggregated from six published series using
      0.05% betamethasone was 87% at 4 weeks and 90% on completion of treatment. Thus,
      the results appear inferior when analysed at 4 weeks but compare favourably with
      those reported for a more potent steroid on completion of the full course of
      treatment. CONCLUSIONS: Even though the triamcinolone cream used in the present
      study is less potent than the more commonly used 0.05% betamethasone valerate
      cream, it could effect comparable improvements in foreskin retractability after 6
      weeks of treatment.

PMID- 11527266
TI  - Costs of accessing surgical specialists by rural and remote residents.
AB  - INTRODUCTION: Access to surgical specialist services by rural and remote
      residents in Australia is limited. Little information is available on the cost to
      rural residents of accessing specialist treatment. The aim of the present study
      was to define the personal costs incurred by country patients in Western
      Australia when accessing specialist surgical services in a rural or metropolitan
      setting. METHODS: A random sample of 50 patients who attended a visiting rural
      surgical service between December 1998 and February 1999 inclusive was recruited.
      In a structured telephone interview patients were asked 40 non-clinical questions
      relating to their recent specialist consultation. The cost of accessing these
      services was determined from time lost from work, distance and travel expenses.
      The same formula was then applied to estimate the cost of attending a base
      metropolitan hospital. The need for an accompanying person was determined from a
      subset of 16 patients who had transferred to metropolitan specialist consultation
      in the previous 12 months. Average waiting list times for consultations and
      common surgical procedures for the visiting service were compared with those for
      a metropolitan-based service. RESULTS: An estimated saving of AU$1,077 was made
      per specialist consultation when accessing a local rather than a metropolitan
      service. Savings were observed in travel time, distance travelled, lost income,
      provision of an escort and waiting time. CONCLUSION: The present study shows that
      the personal costs and difficulties incurred by rural and remote residents when
      accessing specialist treatment can be reduced if a visiting specialist service is
      available.

PMID- 11527267
TI  - Effect of topical glyceryl trinitrate on anodermal blood flow in patients with
      chronic anal fissures.
AB  - INTRODUCTION: Recent studies have highlighted the role of increased internal anal
      sphincter pressure and decreased anodermal blood flow in the pathogenesis of
      chronic anal fissures. The duration of the effect of topical 0.2% glyceryl
      trinitrate (GTN) ointment on anodermal blood flow in fissure and normal areas was
      investigated in patients with chronic anal fissures. METHODS: Six patients with
      chronic anal fissures in the posterior midline participated in the study. Blood
      flow measurements were performed on the anoderm using laser Doppler flowmetry
      before and immediately after the topical application of 0.2% GTN ointment and
      subsequent readings were taken at 5, 15, 30, 45 and 60 min in all four quadrants.
      RESULTS: The mean anodermal blood flow in the fissure region is significantly
      lower than the mean blood flow of the rest of the anoderm before 0.2% GTN
      ointment is applied (228.7 +/- 61.8 flux units vs 439.3 +/- 25.5 flux units,
      respectively; P < 0.05). Immediately after the application of local 0.2% GTN
      ointment there is a significant increase in anodermal blood flow over the anal
      fissure region (457.8 +/- 56.5 flux units; P < 0.05) compared to the rest of the
      anoderm (457.4 +/- 30.8 flux units). This increase is most marked at 5 min post
      GTN ointment application in the fissure area (474.6 +/- 41.1 flux units) and the
      blood flow in the fissure region is consistently above the rest of the anoderm
      for most of the 60 min. CONCLUSION: There is clearly reduced blood flow to the
      chronic anal fissure region compared to the rest of the anoderm. Topical
      application of glyceryl trinitrate ointment seems to significantly improve the
      blood flow to the fissured area in the first hour. This may therefore help in the
      healing of chronic anal fissures.

PMID- 11527268
TI  - Gastric tube graft interposition as an oesophageal substitute.

PMID- 11527269
TI  - Carotid artery dissection: another airbag injury.

PMID- 11527270
TI  - Oesophageal rupture resulting from airbag deployment during a motor vehicle
      accident.

PMID- 11527271
TI  - Repair of major airway injury using albumin-glutaraldehyde glue.

PMID- 11527272
TI  - Left-sided gall bladder: a diagnostic and surgical challenge.

PMID- 11527273
TI  - Management of complicated intrathoracic Riedel's thyroiditis.

PMID- 11527274
TI  - A functional MRI study of three motor tasks in the evaluation of stroke recovery.
AB  - Functional brain imaging studies have provided insights into the processes
      related to motor recovery after stroke. The comparative value of different motor
      activation tasks for probing these processes has received limited study. We
      hypothesized that different hand motor tasks would activate the brain differently
      in controls, and that this would affect control-patient comparisons. Functional
      magnetic resonance imaging (MRI) was used to evaluate nine control subjects and
      seven patients with good recovery after a left hemisphere hemiparetic stroke. The
      volume of activated brain in bilateral sensorimotor cortex and four other motor
      regions was compared during each of three tasks performed by the right hand:
      index-finger tapping, four-finger tapping, and squeezing. In control subjects,
      activation in left sensorimotor cortex was found to be significantly larger
      during squeezing as compared with index-finger tapping. When comparing control
      subjects with stroke patients, patients showed a larger volume of activation in
      right sensorimotor cortex during index-finger tapping but not with four-finger
      tapping or squeezing. In addition, patients also showed a trend toward larger
      activation volume than controls within left supplementary motor area during index
      finger tapping but not during the other tasks. Motion artifact was more common
      with squeezing than with the tapping tasks. The choice of hand motor tasks used
      during brain mapping can influence findings in control subjects as well as the
      differences identified between controls and stroke patients. The results may be
      useful for future studies of motor recovery after stroke.

PMID- 11527275
TI  - Impact of neurorehabilitation on disability in patients with acutely and
      chronically disabling diseases of the nervous system measured by the Extended
      Barthel Index.
AB  - To study the impact of rehabilitation on disability in an unselected patient
      group with acutely and chronically disabling neurologic diseases, the Extended
      Barthel Index (EBI) was determined at the beginning and at the end of the
      rehabilitation stay in all patients admitted to our Neurorehabilitation Centre in
      Valens, Switzerland. Patients who reached the highest possible EBI score at entry
      ("ceiling effect"), with a short stay (<1 week), or with a deterioration due to
      other medical complications were excluded. Finally EBI data of 743 patients could
      be analyzed. The mean EBI at entry was 45 and 51 at discharge. The mean increase
      of the EBI score per week was 1.1 (SD, 1.7). The change of the EBI score was
      analyzed independently in patients with acute neurologic diseases admitted in the
      postacute phase (acute group) and patients with chronically disabling neurologic
      diseases (chronic group). As expected, the increase of the EBI score was higher
      in the acute group than in the chronic group; 80.8% of the acute group patients
      and 42.5% of the chronic group patients showed an increase of the EBI score at
      discharge. Both groups showed a significant EBI gain with a marked shift to
      higher EBI scores at discharge. The mean gain per week was 1.6 in the acute group
      and 0.5 in the chronic group, respectively. Analysis of EBI changes considering
      the different underlying diseases showed the highest increase in patients with
      stroke and traumatic brain injury.

PMID- 11527276
TI  - Assessing motor deficits in neurological rehabilitation: patterns of instrument
      usage.
AB  - To describe current patterns in the use of clinical scales and measurement
      technology for the assessment of motor deficits in neurological rehabilitation.
      Questionnaire, sent to the 2,556 members of the World Forum for Neurological
      Rehabilitation, distributed over 75 countries. Sixty-eight questionnaires were
      returned. Generally, participants indicated that the centres where they were
      based used a number of different clinical assessment scales (median, three), most
      frequently with a small proportion of patients. The (Modified) Ashworth Scale,
      the FIM, and the Fugl-Meyer were used most frequently. Only 35 respondents stated
      that their centre used one or more scales in >75% of their patients, but the
      choice of such routinely applied instruments varied between centres. The
      application of measurement technology was restricted, with video and goniometry
      being used most frequently. The main barriers to more frequent use of assessment
      tools were perceived to be a lack of resources, information, and training. The
      (albeit limited) results from this survey suggest that the assessment of motor
      deficits in neurological rehabilitation is currently mostly qualitative and lacks
      standardisation. More resources and education are required to support a more
      routine application of assessment tools and to integrate measurement technology
      further in neurological rehabilitation to assist in the process of quantification
      of outcomes.

PMID- 11527277
TI  - fMRI response during visual motion stimulation in patients with late whiplash
      syndrome.
AB  - After whiplash trauma, up to one fourth of patients develop chronic symptoms
      including head and neck pain and cognitive disturbances. Resting perfusion single
      photon-emission computed tomography (SPECT) found decreased
      temporoparietooccipital tracer uptake among these long-term symptomatic patients
      with late whiplash syndrome. As MT/MST (V5/V5a) are located in that area, this
      study addressed the question whether these patients show impairments in visual
      motion perception. We examined five symptomatic patients with late whiplash
      syndrome, five asymptomatic patients after whiplash trauma, and a control group
      of seven volunteers without the history of trauma. Tests for visual motion
      perception and functional magnetic resonance imaging (fMRI) measurements during
      visual motion stimulation were performed. Symptomatic patients showed a
      significant reduction in their ability to perceive coherent visual motion
      compared with controls, whereas the asymptomatic patients did not show this
      effect. fMRI activation was similar during random dot motion in all three groups,
      but was significantly decreased during coherent dot motion in the symptomatic
      patients compared with the other two groups. Reduced psychophysical motion
      performance and reduced fMRI responses in symptomatic patients with late whiplash
      syndrome both point to a functional impairment in cortical areas sensitive to
      coherent motion. Larger studies are needed to confirm these clinical and
      functional imaging results to provide a possible additional diagnostic criterion
      for the evaluation of patients with late whiplash syndrome.

PMID- 11527278
TI  - An electromechanical gait trainer for restoration of gait in hemiparetic stroke
      patients: preliminary results.
AB  - Modern concepts of gait rehabilitation after stroke favor a task-specific
      repetitive approach. In practice, the required physical effort of the therapists
      limits the realization of this approach. Therefore, a mechanized gait trainer
      enabling nonambulatory patients to have the repetitive practice of a gait-like
      movement without overstraining therapists was constructed. This preliminary study
      investigated whether an additional 4-week daily therapy on the gait trainer could
      improve gait ability in 14 chronic wheelchair-bound hemiparetic subjects. The 4
      weeks of physiotherapy and gait-trainer therapy resulted in a relevant
      improvement of gait ability in all subjects. Velocity, cadence, and stride length
      improved significantly (p < 0.01). The kinesiologic electromyogram of selected
      lower-limb muscles revealed a more physiologic pattern. The confounding influence
      of spontaneous recovery, the lack of a control group, and the double amount of
      therapy limit the clinical relevance of this study. Nevertheless, the gait
      trainer seems feasible as an adjunctive tool in gait rehabilitation after stroke;
      further studies are needed.

PMID- 11527279
TI  - Putaminal hemorrhage and outcome.
AB  - Twenty-five patients (average age, 65 +/- 4.5 years) with spontaneous putaminal
      hemorrhage were studied to determine any independent predictors as to survival
      and level of disability. Based on the computed tomography (CT) findings, they
      were grouped according to their location and extent of the hemorrhage. The
      thalamus and the caudate were not involved. Univariate and multivariate
      regression analyses were done to determine any potential prognostic indicator.
      The groups were significantly different with regard to volume, intraventricular
      hemorrhage, midline shift, ambient cisterns, hydrocephalus, and disability score
      but not different with respect to pineal shift, side, gender, and age. The
      variables that arose as significant predictors of disability were
      intraventricular hemorrhage, midline shift, hydrocephalus, ambient cistems (all p
      < or = 0.001), pineal shift and age (both p < or = 0.04). Neither gender nor side
      was a significant predictor for disability score (p = 0.92 and p = 0.125,
      respectively). Multivariate regression model included volume, ambient cisterns,
      and age as significant predictors for disability score.

PMID- 11527280
TI  - The estimated cost of managing focal spasticity: a physician practice patterns
      survey.
AB  - The purpose of this study was to estimate the overall cost of managing focal
      spasticity after stroke (CVA) and traumatic brain injury (TBI) and the cost
      impact of individual treatments. Sixty physicians described management strategies
      over six treatment visits for four focal spasticity case studies (one upper and
      one lower extremity case for CVA and TBI). Mean and median per-case costs were
      determined across physicians; median per-case costs of physicians who did or did
      not report use of specific treatments were compared. Mean per-case costs of
      managing spasticity are as follows: CVA upper, $5,131; CVA lower, $5,384; TBI
      upper, $14,615; and TBI lower, $13,966. Median per-case costs for strategies
      including botulinum toxin type A (BTX-A) were less than those without BTX-A in
      CVA upper; median costs for strategies including oral baclofen were more than
      those without baclofen in CVA lower. Fewer total treatments were reported with
      BTX-A than without; more total treatments were reported with baclofen than
      without. No individual treatment had a significant impact on median treatment
      costs in TBI. Physician-reported spasticity management costs are substantial.
      Despite higher drug costs for BTX-A compared with oral therapies like baclofen,
      strategies for managing spasticity in CVA that include BTX-A may cost less than
      those without BTX-A.

PMID- 11527281
TI  - The interrelations between disability and quality of life in patients with
      multiple sclerosis in the area of Bajo Aragon, Spain: a geographically based
      survey.
AB  - Multiple sclerosis (MS) is one of the most disabling diseases in young people,
      but the interrelation between disability and quality of life is poorly
      understood. As individual correlations between disability and the perspective of
      the patient may be weak in individual subjects, the purpose of our work was to
      analyze and correlate quality of life with neurologic impairment and disability
      in all patients with MS from the geographic area of the Bajo Aragon in the
      northeastern region of Spain. A total of 36 patients with a diagnosis of probable
      or clinically definite MS had an average age was 38.1 years (range,17-66 years).
      The majority of them were women (66.6%) and had relapsing-remitting forms
      (83.3%). The Minimal Record of Disability measured neurologic impairments,
      functional limitations, and handicaps. Quality of life was measured by the
      Functional Assessment of Multiple Sclerosis (FAMS) scale. Statistical analysis
      was performed with the Kruskal-Wallis nonparametric test and Pearson's
      coefficient of correlation. The mean EDSS of our cohort was 2.76 (range, 0-9).
      The mean FAMS score was 78.6 (SD, 52.5). We found that patients moderately or
      severely disabled (EDSS >3) showed a significantly decreased satisfaction in
      comparison with the nondisabled or mildly disabled ones. Disability and handicaps
      were significantly related to some items of FAMS: mobility, symptoms, and
      emotional well-being, but not with the remaining items: general contentment,
      thinking and fatigue, family and social well-being, and additional concerns. In
      comparison with patients from other population-based surveys, our patients were
      less disabled and enjoyed a better quality of life. Although we globally observed
      poorer quality of life in more disabled patients, the perspectives of the
      patients did not necessarily agree with disability scales in some domains of
      health. Quality of life should be included in the approach to MS patients if we
      want to provide cost-effective health care.

PMID- 11527282
TI  - Effectiveness of an attention- and memory-training program on neuropsychological
      deficits in schizophrenia.
AB  - The effect of two cognitive remediation procedures developed for closed head
      injury, Attention Process Training (APT) and Prospective Memory Training (PROMT),
      on neuropsychological deficits in schizophrenia was investigated. Six patients
      with schizophrenia, varying in baseline intellectual function and symptoms, were
      studied; three in a remediation condition and three in a nonremediated control
      condition. Results were evaluated individually for each of the three treated
      patients. Two of three remediation-treated subjects showed marked improvement on
      tests of sustained and divided attention. Untreated patients showed little
      evidence of change in neuropsychological test performance across a similar time
      interval, when tested on a subset of the measures administered to remediation
      treated patients. The results of this study are discussed with a view toward
      future studies using larger sample sizes with homogeneous subject populations.

PMID- 11527283
TI  - Critical illness neuropathy.
AB  - Critical illness neuropathy frequently accompanies the septic syndrome in
      intensive care units. Another entity that may occur independently or concurrently
      in critically ill patients is a myopathy, giving rise to difficulties in
      distinguishing between them. The two patients described had sensorimotor axonal
      peripheral neuropathy. Axonopathy as a rule has a poor prognosis for recovery,
      which is slow and often incomplete. There are few reports of the functional
      outcome after rehabilitation therapy. The two patients described had 5-6 weeks of
      active rehabilitation therapy with improvement from moderate/severe disability at
      the onset to slight debility at the end of therapy.

PMID- 11527284
TI  - Unit management of depression of patients with multiple sclerosis using cognitive
      remediation strategies: a preliminary study.
AB  - Multiple sclerosis (MS) is a chronic, often progressive neurologic disorder
      characterized by cerebral and spinal cord lesions. Patients with advanced MS
      often require continuous supervision in a long-term skilled nursing facility.
      Many of these patients experience clinical levels of depression. For this
      experiment, we randomly assigned MS patients living in a skilled nursing facility
      to either a control condition or an extended treatment protocol. The protocol
      consisted of assigning individual certified nursing assistants (CNAs) to each
      patient, in-service training for the CNAs, and the use of memory notebooks. All
      patients completed the short version of the Beck Depression Inventory and several
      measures of cognitive functioning at the start and end of the study. The results
      indicate statistically and clinically significant improvements in the depression
      of patients in the treatment but not in the control condition. These results led
      to recommendations for the treatment of MS patients living in long-term skilled
      nursing facilities and for additional research.

PMID- 11527285
TI  - Neoadjuvant chemotherapy in operable adenocarcinoma of the oesophagus.

PMID- 11527286
TI  - Chemotherapy in oesophageal cancer.

PMID- 11527287
TI  - Squamous cell carcinoma of the oesophagus treated with radiation and 5
      fluorouracil, with and without mitomycin C.
AB  - A retrospective analysis was performed of patients with squamous cell carcinoma
      of the oesophagus without evidence of distant metastases, who were treated with
      radical intent. Between 1981 and 1984, and 1989 and 1991, 98 patients were
      treated with radiation, 5-fluorouracil (5-FU) and mitomycin C; and between 1984
      and 1989, 133 patients were treated with radiation and 5-FU without mitomycin C.
      Actuarial survival and local control were assessed, and prognostic factors were
      identified for both endpoints. The standard dose of radiation prescribed was 52
      Gy to the 95% isodose in 20 fractions over 4 weeks. 5-FU was given by continuous
      infusion as 1 g/m2 (maximum 1.5 g)/day, for 4 days. Patients who received
      mitomycin C were given 10 mg/m2 (maximum 18 mg) on day 1. Survival and local
      relapse-free rates were estimated using the method of Kaplan and Meier, and the
      Cox proportional hazards model was used to evaluate possible prognostic factors,
      including the effect of mitomycin C administration. The median survival was 15.4
      months (95% confidence interval 12.7-17.2) with 31% 2-year survival (standard
      error (SE) 3%), and 13% 5-year survival (SE 2%). In the multivariate analysis,
      lower radiation dose and younger age were the only statistically significant
      prognostic factors for reduced overall survival and reduced relapse-free rate
      respectively. There was no difference in survival (chi(2) = 0.07, 1 degree of
      freedom (df), P=0.79) or local relapse-free rate (chi2 = 0.39, 1 df, P = 0.53)
      between patients treated with or without mitomycin C. The treatment was well
      tolerated. Further studies are required to determine the most effective
      combination of radiation and chemotherapy or other radiation sensitizers for
      squamous cell carcinoma of the oesophagus.

PMID- 11527289
TI  - 5-fluorouracil-induced balanitis in a patient with oesophageal carcinoma.
AB  - We have reported the case history of a patient with balanitis, who was treated
      with 5-FU. Although 5-FU has a wide toxicity profile, balanitis has not been
      reported in association with this therapy.

PMID- 11527288
TI  - Combined results from three phase II trials of neoadjuvant chemotherapy in
      operable adenocarcinoma of the oesophagus.
AB  - Adenocarcinoma of the oesophagus is a systemic disease at presentation in the
      majority of patients. This article analyses the impact of preoperative
      chemotherapy on a cohort of 68 patients. From 1990 to 1996, 68 patients with
      potentially operable adenocarcinoma of the oesophagus were entered into three
      sequential Phase II trials of neoadjuvant chemotherapy with cisplatin/mitomycin
      C/ifosfamide, cisplatin/5-fluorouracil (5-FU) and mitomycin C/cisplatin/5-FU.
      Twenty-four (35%) patients had a radiological (4 complete; 20 partial) response
      to chemotherapy, and 52 (76%) went on to have the primary tumour resected. There
      was only one pathological complete responder. The overall median survival was 13
      months (95% confidence interval (CI) 9-16). Survival for the 28 N(0) patients was
      34 months (95% CI 14-60). The pattern of failure for resected patients was
      predominantly systemic (16/17). These results indicate that neoadjuvant
      chemotherapy followed by surgery for adenocarcinoma of the oesophagus achieves
      excellent local control. The dominance, however, of distant recurrence after
      surgery underlines the fact that, in the majority of patients, the only hope of
      improving results in the future is to develop better systemic therapies.

PMID- 11527290
TI  - Breast cancer: locoregional control and survival.

PMID- 11527291
TI  - The management of menopausal sequelae in patients with breast cancer.
AB  - The use of chemotherapy and tamoxifen for young women with breast cancer results
      in premature menopause in a significant number of patients. Early menopause has
      serious vasomotor, psychological, genitourinary, cardiac and skeletal effects.
      Psychopharmacological and herbal preparations are widely used for the treatment
      of vasomotor symptoms. The incidence of psychological and depressive illness
      following the menopause in women with breast cancer is significantly higher than
      seen with the natural menopause. Targeting this population of patients for early
      diagnosis and psychiatric intervention is recommended. Local vaginal moisturising
      or oestrogen cream would help to alleviate some of the urogenital symptoms.
      Patients whose treatment included Anthracycline chemotherapy or radiation to the
      heart and those with a history of heart disease, should be monitored closely for
      latecardiac complications. Early menopause is the major risk factor for the
      development of osteoporosis. Weight bearing exercise, bisphosphonate or
      calcitonin therapy are all useful in treating osteoporosis. Should a woman with a
      history of breast cancer be given hormone replacement therapy is one of the most
      controversial issues in the oncology field. There are no published prospective
      randomised studies on the subject. The available data suggests an increase of 5%
      of breast cancer related events when hormone replacement therapy is given to
      women with breast cancer. However, in certain situations, this could be given
      after a detailed explanation and documentation. The patient and physician should
      balance the severity of symptoms against the increased breast cancer related
      events and the final decision should be left to the patient.

PMID- 11527292
TI  - Imaging of metastatic breast cancer: distribution and radiological assessment at
      presentation.
AB  - This prospective study was performed to document the distribution of sites of
      disease in breast cancer patients with newly diagnosed metastatic disease, and to
      identify those with assessable or measurable disease by International Union
      Against Cancer (UICC) criteria. Data were collected on a consecutive series of
      100 patients presenting with metastatic breast cancer. Imaging findings recorded
      included whether patients had assessable or measurable disease and which
      potentially assessable sites were rendered unassessable by radiotherapy.
      Radiologically diagnosable complications were recorded. Skeletal metastases
      comprised the majority, with 67 patients having skeletal involvement, although of
      these only 33 (49%) had assessable disease and 24 (36%) measurable disease.
      Sixteen (24%) patients had radiographically occult metastases. Liver ultrasound
      examination showed metastatic disease in 32 patients, of whom 28 (88%) had
      measurable lesions and 12% diffuse disease. Chest radiographs demonstrated
      metastatic disease in 42 patients, with assessable disease in 39 (93%) and
      measurable disease in 18 (43%). In total, 80 patients had radiologically
      assessable disease, with five rendered unassessable by the administration of
      radiotherapy to the only assessable site. Therefore, of the 100 patients, 75%
      (95% confidence interval (CI) 65-83) had radiologically assessable disease, with
      55% (95% 45-65 CI) having measurable lesions by UICC criteria.

PMID- 11527293
TI  - Outpatient follow-up after treatment for early breast cancer: updated results
      after 5 years.
AB  - The value of frequent outpatient follow-up in the first few years after primary
      treatment for early breast cancer is a controversial issue. Schedules involving 3
      4 monthly visits in the first 2-3 years and 6-monthly from years 3-5 are still
      commonplace. In this study we audited such a policy from a single cancer centre,
      identifying a cohort of all 612 patients with early breast cancer (pT(1-3)pN(0
      1)NxM0) referred for adjuvant therapy in 1993. The hospital records were reviewed
      to ascertain patient and tumour characteristics, the surgical and adjuvant
      treatment received, the timing and sequencing of recurrences and their mode of
      detection. Five hundred and five patients had breast conservation surgery. The
      actuarial local recurrence-free survival rate at 5 years in this group was 94.5%.
      Twenty-five of the 31 local recurrences that occurred were the first site of
      relapse. Eight (32%) of these were detected at routine clinic appointments, seven
      (28%) by routine mammography, and nine (36%) were interim referrals. Significant
      risk factors for local recurrence identified were lymph node status (P = 0.03)
      and tumour grade (P = 0.04). One hundred and four patients underwent mastectomy.
      The actuarial local recurrence-free survival at 5 years in this group was 85.4%.
      Nine of the 13 local recurrences were the first site of relapse. Six (66.7%) of
      these were detected at routine appointments. The significant risk factor for
      local recurrence identified was tumour grade (P = 0.03). Overall, 60.1% of
      metastases presented as interim referrals. Nodal status, tumour grade and tumour
      stage were confirmed as significant risk factors for metastasis (P < or = 0.001).
      Hazard rate analysis demonstrated a peak incidence of both local and metastatic
      recurrences in the second year, diminishing thereafter. This peak was largely
      confined to patients with tumours with poor prognostic features. We identified
      only eight patients out of a total of 612 followed up as outpatients for 5 years
      who had local recurrences that were detected at routine appointments and were
      amenable to salvage surgery with the prospect of cure. Therefore it is unlikely
      that a reduction in the intensity of outpatient follow-up in the early years
      after primary treatment will have a significant impact on the overall mortality
      or morbidity of patients with early breast cancer. Other models of follow-up are
      discussed, which could work well provided good communication is maintained
      amongst the health care professionals involved.

PMID- 11527294
TI  - Recurrent locally advanced breast cancer: the treatment of chest wall disease
      with further chemotherapy.
AB  - Locally recurrent advanced breast cancer is associated with significant morbidity
      and one aim of treatment is to control chest wall disease. There are no published
      data on the efficacy of subsequent courses of chemotherapy in this setting. We
      reviewed the case notes of 22 patients who developed locally recurrent breast
      cancer despite having received previous surgery, radiotherapy and one prior
      course of chemotherapy for local disease. These patients were treated with
      further systemic chemotherapy in an attempt to palliate their symptoms and
      control recurrent disease. The overall objective response rate observed with
      chemotherapy was 26% and a further 45% had stabilization of disease during
      treatment. Time to progression of disease was longest with anthracycline-based
      regimens; this decreased with subsequent lines of treatment. Chemotherapy was a
      safe and effective treatment modality in the care of women with locally recurrent
      breast cancer. A prospective database will now be established to collect further
      information on this group of patients, including their quality of life.

PMID- 11527295
TI  - Complete resolution of metastatic breast cancer by withdrawal of hormone
      replacement therapy.
AB  - We report the case history of a patient with a known history of locally recurrent
      breast cancer, who developed metastatic disease while taking hormone replacement
      therapy (HRT). She underwent complete radiographic resolution of disease with no
      treatment other than cessation of the HRT.

PMID- 11527296
TI  - Palliative radiotherapy for lung cancer: is it enough?

PMID- 11527297
TI  - Patients with advanced cancer: a survey of the understanding of their illness and
      expectations from palliative radiotherapy for symptomatic metastases.
AB  - We conducted a pilot study to examine patients' understanding of their illness
      and their expectations for palliative radiotherapy for symptomatic metastases.
      Participants were asked to complete a survey consisting of seven questions prior
      to the initial consultation. Demographic details and information on extent of
      disease were collected. Patients were asked to score their symptom distress using
      the modified Edmonton Symptom Assessment System. Sixty patients participated in
      the pilot study between January and April 1999. Their median age was 68 years
      (range 46-90). The most common primary tumours were lung, prostate and breast.
      Twenty-one patients (35%) believed that their cancer was curable. Twelve (20%)
      expected that palliative radiotherapy would cure their advanced cancer and 23
      (38%) believed that palliative radiotherapy would prolong their lives. Twenty-one
      patients (35%) had concerns about the effectiveness of radiation therapy and
      twenty (33%) had concerns about the side-effects of radiotherapy. Fifty-two (87%)
      were not familiar with the concept of radiation treatment. Forty-seven patients
      (78%) reported that they were not given information about the radiation
      treatment; 51 (85%) were not satisfied with the information that their own
      doctors had provided regarding radiation treatment prior to the consultation at
      our clinic. A significant proportion of the patients in this pilot study had
      misconceptions regarding their illness and unrealistic expectations from
      palliative radiotherapy. We plan to provide educational pamphlets for use in
      referring doctors' surgeries and clinics in order to inform patients of the
      nature, rationale and anticipated benefits and side-effects of palliative
      radiotherapy.

PMID- 11527298
TI  - How accurate are physicians' clinical predictions of survival and the available
      prognostic tools in estimating survival times in terminally ill cancer patients?
      A systematic review.
AB  - The purpose of this review was to examine the accuracy of physicians' clinical
      predictions of survival and the available prognostic tools in estimating survival
      times in terminally ill cancer patients. A MEDLINE search for English language
      articles published between 1966 and March 2000 was performed using the following
      keywords: forecasting/clinical prediction, prognosis/prognostic factors, survival
      and neoplasm metastasis. Searches in CancerLit, EMBASE, PubMed, the Cochrane
      Library and reference sections of articles were performed. Studies were included
      if they concerned adult patients with various cancer histological diagnoses and
      employed clinical prediction and the readily available clinical parameters.
      Biochemical and molecular markers were excluded. Grading of the evidence and
      recommendations was performed. Twelve articles on clinical prediction and 19 on
      prognostic factors met the inclusion criteria. Clinical prediction tends to be
      incorrect in the optimistic direction but improves with repeated measurements.
      Performance status has been found to be most strongly correlated with the
      duration of survival, followed by the 'terminal syndrome', which includes
      anorexia, weight loss and dysphagia. Cognitive failure and confusion have also
      been associated with a shorter life span. Performance status combined with
      clinical symptoms and the clinician's estimate helps to guide an accurate
      prediction, as reviewed in an Italian series. There is fair evidence to support
      using performance status, and clinical and biochemical parameters, in addition to
      clinicians' judgement to aid survival prediction. However, there is weak evidence
      to support that clinicians' estimates alone could be specifically employed for
      survival prediction.

PMID- 11527299
TI  - Predictors of response to strontium-89 (Metastron) in skeletal metastases from
      prostate cancer: report of a single centre's 10-year experience.
AB  - An analysis of prospectively collected data from 75 patients with bone metastases
      secondary to prostate cancer who were treated with strontium-89 injection in a
      single centre over a 10-year period, is presented. The surrogate role of markers
      of disease progression (haemoglobin and prostate specific (PSA) antigen levels;
      number of bone scan-positive sites), symptomatic factors (analgesic intake;
      number of painful bone sites) and history of prior external radiotherapy, were
      analysed to determine whether any parameters had a predictive effect on the
      success of strontium-89 treatment. The success of strontium-89 injection was
      determined by calculating the change in number of sites of bone pain (pain sites)
      and analgesic intake. The outcome was classed as successful in 42 (56.0%)
      patients, unsuccessful in 13 (17.3%) and unchanged in 20 (26.7%). Proportionately
      more of the patients who had 'superscans' on bone scintigraphy at baseline had an
      unsuccessful outcome after a strontium-89 injection (5/7; 71.4%); for those with
      fewer bone scan-positive sites the majority had successful outcomes. Patients
      with a successful outcome had a significantly better survival rate after
      strontium-89 injection. Multivariate analysis showed haemoglobin level, PSA level
      and outcome after strontium-89 treatment to be significant independent prognostic
      variables; no change/unsuccessful outcome, a high PSA level prior to treatment,
      and a low haemoglobin level were associated with poor survival. It is suggested
      that early treatment with strontium-89 (Metastron) in patients with fewer bone
      metastases is more likely to be successful, with a longer time before further
      therapy required.

PMID- 11527300
TI  - Stereotactic radiotherapy for solitary brain metastases.
AB  - PURPOSE: Surgery is considered to be the treatment of choice for patients with
      solitary brain metastases. We report a single-centre experience of stereotactic
      radiotherapy (SRT)/radiosurgery as an alternative to surgery and define
      prognostic parameters that provide for a more rational selection of patients for
      appropriate treatment. PATIENTS AND METHODS: Between 1990 and 1997, 96 patients
      with 106 brain metastases received SRT to a dose of 20 Gy in two fractions (range
      20-30 Gy in 24 fractions) either alone or in combination with whole brain
      radiotherapy. RESULTS: After SRT, 51% of patients had improvement in neurological
      function. The median survival of the 96 patients was 9 months. The Radiation
      Therapy Oncology Group prognostic grouping for patients with multiple brain
      metastases (prognostic factors: age, performance status, systemic metastases,
      status of primary tumour) was applicable to this cohort, with median survivals of
      15, 8 and 2 months for favourable, intermediate and poor prognostic groups
      respectively. CONCLUSION: SRT is a non-invasive method of treatment of solitary
      brain metastases and the outcome is comparable with the results obtained after
      surgical excision. Prognosis is determined by factors defined for patients with
      multiple brain metastases, with performance status being the most important.
      SRT/radiosurgery should be reserved for patients with favourable prognostic
      factors, with a Karnofsky performance status >70, who have a reasonable chance of
      good quality prolonged survival. In future trials, radiosurgery should be
      compared in terms of survival, quality of life and health economics to whole
      brain radiotherapy and surgery.

PMID- 11527301
TI  - Rare cancers.

PMID- 11527302
TI  - Severe anaphylactic reaction to oxaliplatin.

PMID- 11527303
TI  - Oxaliplatin-induced radiation recall: timing not a problem.

PMID- 11527304
TI  - Locally recurrent adenoid cystic carcinoma of the left antrum: response to
      epirubicin, cisplatin and 5-fluorouracil.

PMID- 11527305
TI  - Outcomes of cervix cancer treatments in 1993.

PMID- 11527306
TI  - The "temporal processing deficit" hypothesis in dyslexia: new experimental
      evidence.
AB  - The notion that developmental dyslexia may result from a general, nonspecific,
      defect in perceiving rapidly changing auditory signals is a current subject of
      debate (so-called "temporal processing deficit" hypothesis). Thirteen
      phonological dyslexics (age 10-13 years) and 10 controls matched for
      chronological and reading age were compared on a temporal order judgment (TOJ)
      task using the succession of two consonants (/p/-/s/) within a cluster. In order
      to test the relevance of the temporal deficit hypothesis, the task also included
      two additional conditions where either the two stimuli were artificially slowed
      or the interstimulus interval was expanded. As expected, the TOJ performance was
      significantly poorer in dyslexics than in controls. Moreover, in the "slowed
      speech" condition dyslexics' performance improved to reach the normal controls'
      level, whereas no significant improvement occurred when increasing the
      interstimulus interval. Finally dyslexics' performances, especially on the slowed
      condition, were found correlated with several tests of phonological processing
      (phoneme deletion, rhyme judgment, and nonword spelling tasks). These results
      lend support to the general temporal deficit theory of dyslexia.

PMID- 11527307
TI  - Children with spina bifida perceive visual illusions but not multistable figures.
AB  - We compared 32 children with spina bifida and 32 age-matched controls on two
      classes of illusory perception, one involving visual illusions and the other,
      multistable figures. Children with spina bifida were as adept as age peers in the
      perception of visual illusions concerned with size, length, and area, but were
      impaired in the perception of multistable figures that involved figure-ground
      reversals, illusory contours, perspective reversing, and paradoxical figures.
      That children with spina bifida reliably perceive illusions that rely on
      inappropriate constancy scaling of size, length, and area suggests that their
      brain dysmorphologies do not prevent the acquisition of basic perceptual
      operations that enhance the local coherence of object perception. That they do
      not perceive multistable figures suggests that their visual perception
      impairments may involve not object processing so much as poor top-down control
      from higher association areas to representations in the visual cortex.

PMID- 11527308
TI  - Adult attention-deficit/hyperactivity disorder: neuropsychological correlates and
      clinical presentation.
AB  - We compared the neuropsychological test performance of adult ADHD patients to the
      neurocognitive profiles of control subjects recruited from the general
      population. We administered a neuropsychological test battery consisting of
      measures considered sensitive to either orbitofrontal or dorsolateral-prefrontal
      (DLPF) dysfunction. Orbitofrontal hypoarousal is associated with behavioral
      disinhibition and a relative indifference to punishment. The DLPF region may
      function as a central executive system. Indeed, DLPF dysfunction may underlie
      many of the cardinal symptoms associated with ADHD. We tested the following
      hypotheses: (1) adult subjects meeting DSM-IV criteria for ADHD, predominantly
      hyperactive-impulsive type, would display neuropsychological deficits on tasks
      sensitive to orbitofrontal dysfunction; (2) adult subjects meeting DSM-IV
      criteria for ADHD, predominantly inattentive type, would perform poorly on
      measures sensitive to DLPF dysfunction; and (3) adult subjects meeting DSM-IV
      criteria for ADHD, combined type, would exhibit performance deficits on
      orbitofrontal measures and on DLPF tasks. Results partially confirmed our
      hypotheses. Subtyping ADHD patients revealed important group differences.
      Distinct neurocognitive and clinical profiles were observed.

PMID- 11527309
TI  - Production of narratives: picture sequence facilitates organizational but not
      conceptual processing in less educated subjects.
AB  - Fifty-three healthy older adults were produced stories induced by two types of
      picture stimuli (single picture and picture sequence). Discourse samples were
      analyzed for: (1) percentage of expected main ideas (which reflect conceptual
      processing) and (2) number of transitional markers (which reflect organizational
      processing). Results indicate that the older group (75 to 84 years) produced a
      lower percentage of main ideas and less transitional markers than the younger
      group (65 to 74 years). Both groups also showed better performance in response to
      the picture sequence than to the single picture. For the percentage of expected
      main ideas, however, a superior performance in response to the picture sequence
      was observed only among older subjects with higher (11 to 18 years) but not lower
      (4 to 10 years) levels of formal education. The role of education and the
      importance of stimulus type in discourse-specific tasks are discussed.

PMID- 11527310
TI  - Handedness and depression in university students: a sex by handedness
      interaction.
AB  - Previous research has indicated that there is an increased incidence of left
      handedness in samples of depressed individuals. We administered the Beck
      Depression Inventory (BDI) to a sample of 541 undergraduate students. Left-handed
      males showed significant elevation of BDI scores. It is unlikely that this result
      is due to decreased right hemisphere activity or sex-role conflicts. However, one
      possibility is that known differences in male steroid hormones levels between
      right- and left-handers contributed to this effect. Press

PMID- 11527311
TI  - Word valence, attention, and hemispheric activity in depressed, remitted, and
      nondepressed controls.
AB  - Clinically depressed (n = 20), previously depressed (n = 28), and nondepressed
      control (n = 27) individuals, classified according to a structured clinical
      diagnostic interview, participated in a study employing a modified prior entry
      (Titchener, 1908) procedure to investigate interrelationships among word
      (adjective) valence, visual attention, and cerebral hemispheric activity.
      Overall, positive words were selected more quickly when presented to the right,
      versus left, visual field (RVF, LVF); the opposite pattern was observed for
      negative words. While there was no significant group X Valence X Visual Field
      interaction, planned comparisons revealed that the aforementioned Valence X
      Visual Field interaction was significant only for the nondepressed control group.
      Although the remitted group exhibited an overall pattern similar to the control
      group, the depressed group evinced a pattern in the opposite direction for
      positive words (i.e., quicker in the LVF than the RVF).

PMID- 11527312
TI  - Spatial strategy elaboration in egocentric and allocentric tasks following medial
      prefrontal cortex lesions in the rat.
AB  - We evaluated the role of the medial prefrontal cortex (mPFC) in the elaboration
      of egocentric navigation strategies in a water maze (WM). Lesions of mPFC cell
      bodies was achieved in 21 rats using bilateral injections of ibotenic acid (IA);
      13 control rats were injected with saline. After 17 days, rats had to learn an
      allocentric (using external cues: 10 lesioned, 7 saline rats) or an egocentric WM
      (using internal/kinetic cues: 10 lesioned, 6 saline rats) over six trials in a
      same session. The initial trajectory on the sixth trial was used as an index of
      the elaboration of a navigation strategy. In the egocentric test, lesioned rats
      were more rarely located in the target quadrant than control rats. No differences
      were found between lesioned and control rats in the allocentric test. These
      results show that lesions of the mPFC impairs the capacity to elaborate an
      egocentric navigation strategy.

PMID- 11527313
TI  - Hemispheric processing asymmetries: implications for memory.
AB  - Recent research has demonstrated that memory for words elicits left hemisphere
      activation, faces right hemisphere activation, and nameable objects bilateral
      activation. This pattern of results was attributed to dual coding of information,
      with the left hemisphere employing a verbal code and the right a nonverbal code.
      Nameable objects can be encoded either verbally or nonverbally and this accounts
      for their bilateral activation. We investigated this hypothesis in a callosotomy
      patient. Consistent with dual coding, the left hemisphere was superior to the
      right in memory for words, whereas the right was superior for faces. Contrary to
      prediction, performance on nameable pictures was not equivalent in the two
      hemispheres, but rather resulted in a right hemisphere superiority. In addition,
      memory for pictures was significantly better than for either words or faces.
      These findings suggest that the dual code hypothesis is an oversimplification of
      the processing capabilities of the two hemispheres.

PMID- 11527314
TI  - Imagined and actual limb selection: a test of preference.
AB  - Imagined and actual motor performance were compared to determine what factor(s)
      drive limb selection for programming movements in contralateral hemispace. Forty
      right-handed blindfolded subjects were asked to 'reach' via auditory stimulus for
      a small object placed at multiple locations in hemispace. Two conditions were
      included: arms uncrossed and arms crossed. With the uncrossed condition,
      responses were similar. With arms crossed, subjects had the choice of keeping the
      limbs crossed, reacting to proximity, or uncrossing the arms to reach
      ipsilaterally. In this condition subjects 'imagined' that they would maintain the
      crossedposition and reach with the hand closest to the stimulus in both right and
      left hemispace. However, during 'actual' reaching, responses differed. For left
      field stimuli, participants kept the arms crossed, but in response to right-field
      stimuli, subjects preferred to uncross the limbs in order to reach with the
      dominant hand. These findings suggest that while motor dominance is the primary
      factor in limb choice for action in ipsilateral hemispace, it appears that object
      proximity drives limb selection for reaching in contralateral hemispace.

PMID- 11527315
TI  - Number-Stroop performance in normal aging and Alzheimer's-type dementia.
AB  - The number-Stroop paradigm was used to investigate changes in the inhibitory
      system and in numerical processing in healthy elderly and individuals with
      dementia of Alzheimer's type (DAT). The size-congruity effect (i.e., relative to
      neutral trials, incongruent pairs interfere and/or congruent pairs facilitate
      either numerical or physical comparison) was found in all groups, though the
      pattern of interference and facilitation varied across them. Overall, the
      selective attention breakdown was reflected by the increase in interference shown
      by the older group and the DAT group. On the other hand, the observation of a
      standard laterality effect andof automatic numerical processing in all groups
      suggests that access and retrieval of numerical information is relatively
      resistant to cognitive deterioration.

PMID- 11527316
TI  - Letter and number writing in agraphia: a single-case study.
AB  - The gradual recovery of writing abilities of a patient whose processing of Arabic
      numerals and alphabetic script evolved differently over time is reported. Writing
      of multidigit numerals was achieved when writing of letters was nil. However,
      despite an initial advantage for numbers, the final examination disclosed fluent
      and correct writing of letters and words together with specific syntactic
      difficulties in complex Arabic numerals. The differential improvement for Arabic
      and alphabetic stimuli is partly explained in terms of different processing
      requirements rather than in terms of script-specific mechanisms only.

PMID- 11527317
TI  - Neuropsychological impairments in the syndromes of schizophrenia: a comparison
      between different dimensional models.
AB  - This study investigates the associations between the different symptom dimensions
      of schizophrenia and neuropsychological performances. Globally, the results
      replicate previously described associations. The "negative" dimension correlates
      with impaired sustained attention and working memory, thus suggestive of
      dorsolateral frontal cortex dysfunction. "Disorganization" correlates with the
      ability to inhibit proactive interference. thus with ventromedial frontal
      dysfunction. The results also add support to the view that the "psychotic"
      dimension described in three-dimension models includes in fact two distinct
      dimensions, (1) "hallucinations," here associated to episodic memory measures,
      and (2) "delusions", here associated to visuospatial attention, thus suggestive
      of mediotemporal and posterior neocortical dysfunction, respectively.

PMID- 11527318
TI  - Left-side infant holding: a test of the hemispheric arousal-attentional
      hypothesis.
AB  - When asked to hold a young infant in their arms, most adults hold on the left
      side (Harris, 1997). In a prior study, we found the same bias when we asked
      adults merely to imagine holding an infant in their arms (Harris, Almerigi, &
      Kirsch, 1999). It has been hypothesized that the left-side bias is the product of
      right-hemisphere arousal accompanying certain aspects of the act, causing
      attention to be driven to the contralateral, or left, side of personal space.
      Left-side holding, whether actual or imagined, thus would be consistent with the
      direction to which the holder's attention has been endogenously directed. We
      tested this hypothesis by giving 250 college students the "imagine-holding" task
      and then, as an independent measure of lateralized hemispheric arousal, a 34-item
      Chimeric Faces Test (CFT). On the "imagine" test, a significant majority reported
      a left-side hold, and, on the CFT, left-side holders had a significantly stronger
      left-hemispace bias than right-side holders, although both left- and right side
      holders had left-hemispace CFT biases. The results thus support the attentional
      arousal hypothesis but indicate that other factors are contributing as well.

PMID- 11527319
TI  - Exploring the contribution of the cerebral hemispheres to language comprehension
      deficits in adults with developmental language disorder.
AB  - A divided visual field, priming paradigm was used to observe how adults who have
      a history of developmental language disorder (DLD) access lexically ambiguous
      words. The results show that sustained semantic access to subordinate word
      meanings (such as BANK-RIVER), which is seen in control subjects, is disrupted in
      the right cerebral hemisphere for this special population of readers. In the left
      hemisphere, only the most dominant meaning of the ambiguous word shows sustained
      priming in both controls and DLD participants. Therefore, for the DLD readers the
      subordinate meanings of words are not primed in either hemisphere and, thus, may
      not be available during online processing and integration of discourse. This
      right hemisphere lexical access deficit might contribute to the language
      comprehension difficulties exhibited by adult readers with a history of DLD.

PMID- 11527321
TI  - Are text and tune of familiar songs separable by brain damage?
AB  - The recognition of text and tune in songs was examined in a music-agnosic patient
      and five matched controls. Listeners had to focus on one component of the song at
      a time (text or music) and had to decide whether the component was familiar or
      unfamiliar. Songs were either matched (i.e., an original familiar or an original
      unfamiliar song) or mismatched (a combination of a familiar component with an
      unfamiliar one). Normal listeners displayed response patterns that are congruent
      with those obtained previously in different experimental settings and which
      showed that text and tune are difficult to separate. Data collected in the
      patient, however, suggest some independence between text and music in songs.
      Moreover, the usual asymmetry in favor of text was much reduced when later verses
      were used. Overall, the results are interpreted as revealing strong association,
      not integration, between the musical and the verbal component of familiar songs.

PMID- 11527320
TI  - Patterns of apraxia associated with the production of intransitive limb gestures
      following left and right hemisphere stroke.
AB  - The model of apraxia proposed by Roy (1996) states that three patterns of apraxia
      should be observed across pantomime and imitation conditions. In the present
      analysis the frequency and severity of each pattern of apraxia were examined in a
      consecutive sample of left-(LHD) and right-hemisphere-damaged (RHD) patients
      during the production of intransitive limb gestures. The results indicated that a
      significant proportion of LHD and RHD patients were selectively impaired in
      formulating the ideational component of intransitive limb gestures.

PMID- 11527322
TI  - The role of nasals in reading: a normative study in French.
AB  - Dual-route models of reading assume that reading can be done in two ways. A most
      common lexical route, on the one hand, allows regular and irregular words to be
      read while a second sublexical route allows nonwords and novel words to be read.
      A graphemic processing stage in sublexical reading is assumed to assemble the
      individual letters of a word or a nonword into multiletter graphemes prior to
      grapheme-phoneme conversion. The purpose of this study was to determine whether
      vowel/nasal clusters required as much time to be processed asvowel/vowel and
      consonant/consonant clusters in sublexical nonword reading in French. Results
      indicate that nonwords that contain vowel/nasal clusters are read significantly
      faster than nonwords comprising vowel/vowel and consonant/consonant clusters.
      Furthermore, nonwords that contain single-letter graphemes are read significantly
      faster than nonwords comprising vowel/nasal clusters and nonwords comprising
      vowel/vowel and consonant/consonant clusters. These results taken as a whole
      support the idea that nasals act as diacritic marks rather than being processed
      by means of a graphemic parsing procedure.

PMID- 11527323
TI  - Factors predicting success in picture naming in Alzheimer's disease and primary
      progressive aphasia.
AB  - The aim of the present study was to determine the predictive value of all
      important variables in the picture naming performance of 8 patients with probable
      Alzheimer's disease (AD) and 8 patients with primary progressive aphasia (PPA).
      The experimental investigation controlled for (i) visual complexity, (ii) name
      agreement on dominant response, (iii) age of acquisition, (iv) frequency, (v)
      word length, (vi) concept familiarity, and (vii) category membership. The results
      of the multiple regression analyses showed that age of acquisition and name
      agreement were significant for 10/16 subjects. Visual complexity, frequency,
      familiarity, and category were also significant for four patients respectively.
      Word length had no effect. These results are at variance with those of series of
      patients with AD (Gaillard et al., 1998) and with PPA (Lambon Ralph et al., 1998)
      where concept familiarity was found to be one of the most predictive factors of
      naming success.

PMID- 11527324
TI  - Lexical and semantic factors influencing picture naming in aphasia.
AB  - Picture naming requires early visual analysis, accessing stored structural
      knowledge, semantic activation, and lexical retrieval. We tested the effect of
      perceptual, lexical, and semantic variables on the performance of aphasics in
      picture naming and assessed prevalence of natural categories vs artifact
      dissociations. Forty-nine aphasics were asked to name 60 pictures, from three
      natural (animals, fruits, and vegetables) and three artificial categories (tools,
      furniture, and vehicles). For each item visual (drawing complexity, image
      agreement), semantic (prototypicality, concept familiarity) and lexical variables
      (word frequency, name agreement) were available. The effect of these variables
      showed individual differences; altogether, visual complexity had little
      influence, whereas lexical and semantic variables were more influential. Name
      agreement was most important, followed by word frequency. On a multiple single
      case analysis 10 patients (20%) showed a natural/artificial category
      dissociation. Five of the six subjects faring better with artifacts were males,
      and all of four patients faring better with natural categories were females.
      Interpretations of this finding are discussed.

PMID- 11527325
TI  - Refutation of Poffenberger's inference: an existence proof and a countermodel.
AB  - Interhemispheric relay time (IHRT) is inferred from simple (visual) reaction time
      (SRT) by subtracting SRTs in ipsilateral hand-field conditions from SRTs in
      contralateral hand-field conditions. This index, the "crossed-uncrossed
      differential" (CUD) is a synonym of IHRT in the current literature. The CUD has
      been shown to be significantly moderated by experimental variables, including
      attentional. One reason the CUD = IHRT hypostasy persists today is that no
      experimental manipulation has yet been able to generate a significantly negative
      CUD in a subject manifesting a significant positive CUD in classical conditions.
      We implemented an experimental manipulation, in SRT, consisting of increasing
      complexity of the response after the initial key press required at detection. In
      a very large scale single-case experiment, we found that the CUD thus went from
      significantly positive in classical SRT to significantly negative in the
      increased response load condition.

PMID- 11527326
TI  - Mixed-case effects in lateralized word recognition.
AB  - Effects of case alternation and word length were studied in a lateralized visual
      lexical decision task. The previously reported visual field and word length
      interaction was found for upper- and lowercase presentations, but not for MiXeD
      CaSe, where both fields were affected by word length. We discuss the results in
      light of two contrasting models of lateralized word recognition.

PMID- 11527327
TI  - Four hours of paradoxical sleep deprivation impairs alternation performance in a
      water maze in the rat.
AB  - Sixteen rats were deprived of paradoxical sleep (PS) for 4 h using the "flower
      pot" technique and 16 other served as yoked controls. PS-deprived and control
      rats then had to learn a water maze using either a standard allocentric
      configuration (i.e., finding the submerged platform using external cues; n =
      6/group) or an alternation version (goal platform alternating between two
      locations; n 10/group). Rats were submitted to six trials with a cutoff time of
      60 s and an intertrial interval of 5 min. Criterion was set as two consecutive
      successful completions. PS-deprived rats made more quadrant entries and took more
      time to reach criterion on the alternation task than control rats while both
      groups were equal on the allocentric task. Based on lesion studies (Ethier et
      al., this issue) we propose that tasks that require an intact medial prefrontal
      cortex are particularly sensitive to PS deprivation.

PMID- 11527328
TI  - Intensive training of phonological skills in progressive aphasia: a model of
      brain plasticity in neurodegenerative disease.
AB  - Three patients with a typical syndrome of nonfluent primary progressive aphasia
      (Mesulam's syndrome) were trained daily with a remediation protocol including
      auditory exercises specifically designed to involve several aspects of
      phonological processing, a domain known to be specifically affected in the
      condition. The speech content of the exercises was based on the temporal theory
      of phonological processes according to which increasing the duration of formant
      transition should facilitate phoneme discrimination and phoneomic awareness.
      Significantly improved performance on the trained tasks was demonstrated in the
      three patients. Improvement further generalized to other tasks such as nonword
      repetition and reading. We conclude that such results (1) argue for using
      intensive focused therapy of language impairment in neurodegenerative disorders,
      (2) may constitute a good model of brain plasticity in neurodegenerative
      disorders in general, and (3) support theories of phonological processing
      emphasizing temporal features of the auditory signal.

PMID- 11527329
TI  - Is the optimal viewing position in reading influenced by familiarity of the
      letter string?
AB  - An optimal viewing position (OVP) for word recognition has been proposed by
      several authors. The location of this position would be located at the center of
      the word or just left of it. Several hypotheses ranging from perceptual to
      hemispheric factors have been proposed to explain this phenomenon. In the
      experiment presented here, the effect of the nature of the stimulus was tested:
      word, pseudo-word, or nonword on the existence and location of this position.
      Little research has investigated this issue. Five-letter words, pseudo-words, and
      non-words were presented, with the subject fixating initially on one of the five
      possible letter positions. The number of letters correctly identified and reading
      performance were recorded for each stimulus. Results show that an initial
      fixation on the third letter entails better letter identification for all kinds
      of stimuli. However, in terms of reading, only word reading benefit from a
      fixation on the third letter. These results are discussed in relation to the
      different hypotheses of OVP in reading. These are (1) hemispheric specialization,
      (2) reading habits, and (3) lexical constraints.

PMID- 11527330
TI  - Semantic information is used by a deep dyslexic to parse compounds.
AB  - We report a case study of a 48 year-old patient, J.O., who was tested 20 years
      after the removal of a tumor in the left temporal-parietal region. This surgery
      and subsequent radiation resulted in right side paralysis and numerous language
      problems. Tests of J.O.'s single word reading abilities indicate that she could
      be classified as a deep dyslexic with over 16% of her errors in word naming
      having a clear semantic relationship with the target word (Coltheart, 1980). We
      examined her ability to read compound words aloud and following Libben (1993) we
      provide evidence that J.O. is a second case in which there is obligatory access
      of morphological constituents of compound words. These data are discussed within
      the context of Libben's (1998) compound word processing model.

PMID- 11527331
TI  - Some quick arithmetic.
AB  - Mathematical abilities for the four simple arithmetic operations were studied on
      a sample of 53 female right-handers. True and false statements were presented
      auditorily and a manual response was required as to the trueness of the
      statements. Response times, accuracy, and laterality index showed no significant
      ear advantage, but the responses to true statements were significantly faster
      than to the false ones. The shortest response times were found for addition
      problems, and the longest for subtractions. The correlation between the size of
      the difference between the two operands and response time was not conclusive but
      the trend was unexpectedly positive.

PMID- 11527332
TI  - Handedness and immune function.
AB  - Geschwind, Galaburda, and Behan (GBG) have suggested that in utero levels of
      testosterone influence both cerebral and immune system developments (Geschwind
      and Behan, 1982; Geschwind and Galaburda, 1984; Geschwind and Galaburda, 1985).
      According to this theory, high levels of testosterone result in greater
      incidences of left-handedness, deviations from standard distribution of cerebral
      functions (known as anomalous dominance), and increased autoimmune dysfunction.
      While the original data supported these assertions, more recent tests of the
      hypothesis have been equivocal. One criticism of these studies is that the
      definition of both handedness and anomalous dominance are too vague. It was one
      of the aims of this project to investigate and clarify the GBG model by examining
      four different aspects of handedness as well as a more direct measure of
      anomalous dominance. In order to extend the GBG model, degree of left-handedness,
      general immune system functioning, and current testosterone levels were also
      examined. First, it was predicted and found that left handers had a higher
      incidence of autoimmune diseases in their immediate families than did right
      handers. Second, those left handers with an incidence of at least one autoimmune
      disease were more strongly left-handed than were those with no incidence of
      autoimmunity. Finally, it was observed that higher testos terone levels were
      supportive of general immunity. The present findings both support and expand the
      GBG model.

PMID- 11527333
TI  - Productive syntax abilities in Huntington's and Parkinson's diseases.
AB  - This study examined syntactic changes in the spoken discourse of patients with
      Huntington's (HD) or Parkinson's disease (PD) and explored possible relationships
      between their syntactic changes and concomitant cognitive and motoric symptoms.
      Patient and control groups participated in a conversational discourse activity
      and completed a battery of standardized speech and cognitive tests. The HD group
      used shorter and fewer grammatically complete utterances than their healthy, age
      matched peers, whereas there were no significant syntactic differences between PD
      patients and their healthy, age-matched peers or between PD and HD patients.
      Productive syntax abilities in HD and PD were meaningfully related to both
      neuropsychological and motor speech changes. These findings indicate that
      patients with subcortical disease, at least those with HD, may present with
      language production deficits and that these deficits are most likely the product
      of not only motor speech limitations (i.e., dysarthria) but also underlying
      cognitive impairments.

PMID- 11527334
TI  - Unilateral hemispheric activation does not affect free-viewing perceptual
      asymmetries.
AB  - Strong leftward perceptual biases have been reported for the selection of the
      darker of two left/right mirror-reversed luminance gradients under free-viewing
      conditions. This study investigated the effect of unilateral hemispheric
      activation on this leftward bias in two groups of dextrals (N = 52 and N = 24).
      In Experiment 1, activation was manipulated by asking participants to tap with
      their left or right fingers along their midline. In Experiment 2, participants
      clenched their left or right hands in their respective hemispaces. Participants
      selected the stimulus that was darker on the left-hand side 73% of the time.
      Despite manipulations of activation strength and hemispace, activation had no
      effect on the asymmetry. If activation was important, the leftward bias should
      have been enhanced when the left hand/right hemisphere was active and reduced (or
      reversed) when the right hand/left hemisphere was active. The contribution of
      left-to-right scanning biases to free-viewing perceptual asymmetries is discussed
      as an alternative.

PMID- 11527335
TI  - Preparation and motor potentials in chronic tic and Tourette syndromes.
AB  - Many studies have found that people with tic disorder show more difficulty when
      inhibiting an automated than a controlled response. Furthermore, although normal
      motor threshold and excitability are present, but reduced or impaired, motor
      inhibition seems manifest in patients with tic. In order to localize this
      inhibition impairment in tic disorder the present study examine two response
      locked ERPs: the Bereitschaft (preparation BP) and the motor potentials (MP). The
      simple tic group showed faster BP latency and smaller amplitude than control and
      complex tic group and did not show a corresponding change in values with practice
      or with automated or controlled condition. The MP amplitudes revealed that
      whereas both controls and complex tic disorder showed a decrease in amplitude
      during control condition for both blocks, simple tic showed larger amplitude. Our
      ERP results are in agreement with RT results of a previous study. The explanation
      could lie with modulation in motor excitation inhibition circuits and seems worse
      in simple tics where the movements are more automatic and nonvoluntary.

PMID- 11527336
TI  - The isomorphic mapping hypothesis: evidence from Korean.
AB  - This paper evaluates the relative merits of the trace deletion hypothesis, which
      attributes agrammatic comprehension difficulties to the loss of traces, and the
      isomorphic mapping hypothesis, which proposes that agrammatics have difficulty
      understanding sentences in which there is a nonisomorphic mapping between the
      syntactic representation and the corresponding event in the real world. (The two
      are isomorphic if the order of NPs reflects the place of entities in the event's
      'action chain.' Since agents act on themes and transmit them to goals, the agent
      theme-goal order is isomorphic with the corresponding event but the agent-goal
      theme order is not.) The two hypotheses contrast in the predictions they make
      concerning goal-theme and theme-goal patterns in Korean: the TDH predicts
      degraded performance on the theme-goal structure (which is derived from the goal
      theme structure); the IMH predicts difficulties on the goal theme structure,
      since it is nonisomorphic. Results of a comprehension study involving four Korean
      Broca's aphasics provide strong support for the IMH over the TDH.

PMID- 11527337
TI  - Language evolution in children with cochlear implants.
AB  - The capacity to incorporate significant words into the existing vocabulary and to
      use these words to form sentences with more mature syntactic structures emerges
      over a considerable time course in young deaf children who have undergone a
      cochlear implantation. The purpose of this follow-up study is to document the
      nature and time span of language production--in morphosyntactic and lexical
      skills--when a child's first experience with language sounds is provided
      artificially through electrical stimulation. To examine the development of these
      two aspects of linguistic processing, five deaf French children, all enrolled in
      similar postimplantation educational settings, were individually assessed at 6
      month intervals over a period of 18 months. Computerized analyses were derived
      from their spontaneous speech in a 20-min standardized play session. Results for
      mean length of utterance and vocabulary revealed gradually improving performance
      for most children, in spite of the generally low starting point. Both measures of
      production nevertheless remained well below the norms established for normally
      hearing children. Although the achievement of higher production scores, which
      underlies more effective interpersonal exchanges, is evident after only 1 year of
      device use, it is clear that improvement does not always occur at the same pace,
      as shown by two of the children. This emphasizes the importance of longitudinal
      studies in documenting intersubject variability and intrasubject stability
      throughout the experience with an implant.

PMID- 11527338
TI  - Short-term memory impairment and unilateral dichotic listening extinction in a
      child with Landau-Kleffner syndrome: auditory or phonological disorder?
AB  - The neuropsychological profile of a child with a Landau-Kleffner syndrome is
      presented here. The observed cognitive difficulties included verbal short-term
      memory and seemed partially compensated for when the experimental assessments
      bypassed the auditory channel. This case study is especially challenging since
      the child, whose phonological skills were quite efficient and who exhibited a
      dichotic listening unilateral extinction, had developed average reading and
      spelling abilities. The fact that B.E.'s performance on memory tasks was quite
      poor when the stimuli were presented auditorily and more efficient when the
      stimuli were presented visually, strongly suggests that the observed memory
      impairment was due to a deficit at the level of cortical auditory processing.
      B.E.'s phonological skills were efficient, suggesting a neuropsychological
      dissociation between phonological ability and auditory processing. The fact that
      B.E. dramatically recovered language and easily acquired reading and spelling
      accounts for the hypothesis that compensatory strategies allowed him to develop
      phonological skills from predominantly visual input.

PMID- 11527339
TI  - Language production and comprehension in an adult with ACoA syndrome.
AB  - This study explored the prediction that cases with anterior communicating artery
      (ACoA) syndrome will exhibit deficits in higher-level language production and
      comprehension. A 65-year-old adult male with a history of ACoA syndrome was
      tested on higher-level linguistic tasks. The patient's performance on discourse
      comprehension. discourse production, and linguistic ambiguity comprehension tasks
      was impaired.

PMID- 11527340
TI  - Brain and face: communicating signals of health in the left and right sides of
      the face.
AB  - In human communication and mate selection the appearance of health sends signals
      regarding biological fitness. We compared the appearance of health in the sides
      of the face to previous results on left-right facial asymmetry in the appearance
      of beauty (1). The stimuli were created by aligning the left and right sides of
      the face each with its own mirror image. Here, participants viewed 38 pairs of
      left-left and right-right faces and judged which member of the pair looked
      healthier. No significant interaction emerged between decision (health vs
      attractiveness) and face side. Rather, in women's faces right-right was
      significantly more healthy and attractive than left-left, while in men's faces
      there was no significant left-right difference. In biology and evolution, health
      and beauty are closely linked and the findings here confirm this relationship in
      human faces.

PMID- 11527341
TI  - Pattern of intrusions in verbal recall: comparison of Alzheimer's disease,
      Parkinson's disease, and frontal lobe dementia.
AB  - Although some researchers have suggested that intrusions in word list learning
      are more frequent in Alzheimer's disease, recent studies have shown that this
      might not be true. In fact, intrusions are common in many neurological
      degenerative diseases. The goal of the present study was to examine the types of
      intrusions made by three groups of patients, namely patients with Parkinson's
      disease (PD), Alzheimer's disease (AD), and dementia with prominent frontal lobe
      semiology (FD). Although PD patients learned more words (trials 1 to 5 on the
      RAVLT) than the two other groups, there was no significant difference in the
      total number of intrusions. However, significant differences between groups were
      observed for nonrelated intrusions, the proportion of PD patients (15.4%) being
      lower than the proportion of AD (45.5%) and FD (45.8%) patients with this type of
      intrusions. No other type of intrusions (same category, recurring, phonemic)
      significantly differentiated between the three groups. The proactive interference
      effect (PI), measured as the difference between first recall of list A and list B
      recall, was stronger in PD than in the two other groups, reflecting the strong
      positive correlation between total number of words recalled on the RAVLT and
      severity of the PI effect. Prior list intrusions (intrusions from list A while
      recalling list B items) were significantly more pronounced in FD than in the two
      other groups. Finally, free associations (series of intrusions related to one
      another but not to the target items) were observed almost exclusively in FD
      patients. These findings illustrate some qualitative differences between various
      neurological degenerative diseases. They also stress the marked similarities
      between AD and FD with regards to verbal learning.

PMID- 11527342
TI  - Impaired short temporal interval discrimination in a dyslexic adult.
AB  - The ability to discriminate short temporal intervals was examined in a dyslexic
      adult (E.C.) and six matched controls. Listeners had to decide whether the second
      interval was shorter or longer than a standard (target) interval. Each interval
      was defined as the silent duration between two successive brief tones. Eight
      target intervals were used, ranging from 100 to 1,200 ms in duration. At each
      target interval, the differential threshold (DL) for duration was assessed, with
      the use of an adaptive psychophysical procedure. The results show that E.C.'s
      differential threshold values were much larger than those of controls. Moreover,
      the slope estimates covering the duration range from 100 to 800 ms indicated that
      in comparison to controls, E.C.'s differential threshold increased dramatically
      as the target duration increased. Thus her timing impairment becomes more
      pronounced with increasing duration. This timing deficit is consistent with other
      studies that have found temporal processing deficits associated with dyslexia.

PMID- 11527343
TI  - Prosopagnosia: a case study involving problems in processing configural
      information.
AB  - An ongoing issue in face recognition research is whether holistic face processing
      relies on the segregation of local discrete facial parts. Evidence in favor of
      the holistic-plus-parts view stems from a recent study reported by Arguin and
      Saumier (1999), who show that the priming effects of individual facial parts
      (i.e., eyes, nose, mouth, orcontour) depends on the presence of configural
      information and that the magnitude of priming augments as the number of facial
      parts serving as primes increase. The present study demonstrates that these
      global processing effects are absent in a prosopagnosic patient (A.R.), who shows
      no priming from single face parts and a linear increase in the magnitude of
      priming as a function of the number of parts presented. These findings indicate
      that A.R. is incapable of integrating individual facial parts into a global
      facial configuration ant that this is likely at the root of her prosopagnosia.

PMID- 11527344
TI  - Contribution of visual and semantic proximity to identification performance in a
      viral encephalitis patient.
AB  - Identification deficits were investigated in F.S., a patient with herpes simplex
      viral encephalitis. F.S.'s confrontation naming abilities were assessed for
      multiple repetitions of 12 line drawings of artifacts. Six of the line drawings
      consisted of psychologically "close" objects (i.e., objects that share many
      visual and semantic features with other objects) and 6 were psychologically
      "disparate" objects (i.e., objects that share few, if any, visual and semantic
      features with other objects). F.S. correctly named all of the objects from the
      "disparate" category but only 47% of the objects from the "close" category. We
      also tested F.S. using novel, computer-generated shapes that were paired with
      artifact labels. We paired semantically close or disparate labels to shapes and
      F.S. attempted to learn these pairings. Overall, F.S.'s shape-label confusions
      were most detrimentally affected when we used labels that referred to objects
      that were visually close and semantically distinct. Results indicate that, at
      least for our patient, visual similarity contributed the most to his
      identification errors.

PMID- 11527345
TI  - Executive deficits appearing in the initial stage of Alzheimer's disease.
AB  - The presence of executive deficits has been sought at a stage of Alzheimer's
      disease where currently used neuropsychological batteries could not yet
      distinguish Alzheimer's patients from normal age- and education-matched controls.
      This study shows that, at this early stage, those patients that 6 months later
      are found to show clear signs of Alzheimer's had been significantly worse than
      normal controls in an executive function task adapted from the Brown-Peterson
      procedure.

PMID- 11527346
TI  - Stimulus-specific neglect in a deep dyslexic patient.
AB  - We report a patient (B.V.) who appears to suffer from two dyslexic disorders.
      First, B.V. showed a severe impairment in reading aloud nonwords (e.g., reading
      TREST as TREE), in addition to making several semantic errors when reading aloud
      words (e.g., reading ILL as SICK) and in picture naming (e.g., responding KNIFE
      to a picture of a FORK). These results suggest that B.V. suffers from deep
      dyslexia. Second, B.V. showed an impairment in reading the final letters of both
      words and nonwords (e.g., reading SHOWN as SHORT and reading PROGE as PROOF).
      Thus, it appears that B.V. also suffers from neglect dyslexia. We discuss how
      these two forms of dyslexia could be interacting to account for B.V.'s pattern of
      errors in reading aloud words and nonwords and in picture naming.

PMID- 11527347
TI  - Feature processing and superiority of three-quarter views in face recognition.
AB  - The specificity of face recognition is usually related to the hypothesis that it
      could be based mainly on global processing of the whole face. However, this does
      not mean that more analytic processes, like the local processing of some
      features, could not play a role in the recognition process in some circumstances.
      An experiment was conducted with 18 normal subjects in order to evaluate the role
      of analytic processes in the recognition of faces viewed from different angles.
      Makeup was applied to eyes and lips to enhance local processing (local cue). We
      found a positive effect of the makeup cue, which could be due to better
      recognition when the shape of eyes and lips are highlighted. Also, we found
      better recognition with left-sided views compared to right-sided views. Finally,
      the makeup effect was significant in left three-quarter views but not in right
      three-quarter views. If this effect is due to analytic processing of some facial
      features, it could be related to a left hemisphere operation.

PMID- 11527348
TI  - Postnatal development of lateralized motor preference in the African grey parrot
      (Psittacus erithacus).
AB  - The parrot appears to provide a potentially unique animal model of handedness in
      humans, but few (if any) observational studies of early postnatal development of
      postural/motor asymmetries have been published. We studied three African Grey
      hatchlings, raised without human physical contact, for the first 5 months of
      life. All three animals failed to show consistent postural and/or motor
      asymmetries until the end of the 4 postnatal week. These results appear to be
      comparable to data from prior studies with human infants. Delayed development of
      lateral motor and/or postural preferences may represent an evolutionarily
      adaptive strategy for altricial animals.

PMID- 11527350
TI  - The mind and brain scholar as a hitchhiker in the post-Gutenberg galaxy:
      publishing at 2000 and beyond.
AB  - Electronic journal (e-journal) publishing has started to change the ways we think
      about publishing. However, many scholars and scientists in the mind and brain
      sciences are still ignorant of the new possibilities and ongoing debates. This
      paper will provide a summary of the issues involved, give an update of the
      current discussion, and supply practical information on issues related to e
      journal publishing and self-archiving relevant for the mind and brain sciences.
      Issues such as differences between traditional and e-journal publishing, open
      archive initiatives, worldwide conventions, quality control, costs involved in e
      journal publishing, and copyright questions will be addressed. Practical hints on
      how to self-archive, how to submit to the e-journal Psycoloquy, how to create an
      open research archive, and where to find information relevant to e-publishing
      will be supplied.

PMID- 11527349
TI  - Information processing speed deficits may be better correlated with the extent of
      white matter sclerotic lesions in multiple sclerosis than previously suspected.
AB  - Despite frequent use of the Paced Auditory Serial Addition Test (PASAT; Gronwall,
      1977) for examining information processing speed (IPS) deficits in multiple
      sclerosis (MS), prior literature on the relationship between PASAT performance
      and severity of brain disease has been contradictory. In the present study, we
      found that PASAT performance is moderately well correlated with the total area of
      sclerotic brain lesions in MS patients only if a modified scoring method (mean
      "dyad" score; Snyder et al., 1993), but not the standard scoring method, is
      applied. We conclude that the PASAT remains a useful measure of IPS in MS, if a
      flaw in the typical scoring technique for this test is corrected. In our sample
      of 41 MS patients, for every one point decrease in mean dyad score, total lesion
      area increased by 364.08 mm2 on average, after controlling for age, sex, and
      education. IPS deficits are more severe for patients with greater brain disease,
      due to increased disruption of the white matter pathways that likely support the
      parallel distributed processing of complex information by geographically distant
      brain regions.

PMID- 11527351
TI  - Global cognitive decline in schizophrenia with remission of symptoms?
AB  - The relation of symptoms to cognitive dysfunction in schizophrenia is still
      controversial. This study was aimed (i) at verifying if a homogeneous sample of
      10 young treated outpatients in remission from psychotic symptoms displays a
      characteristic pattern of cognitive dysfunction and (ii) at testing the issue of
      a general cognitive impairment. The neuropsychological performance of the
      patients was confronted with a large control group by means of Equivalent Scores,
      a normative method widely used in Italy, which allows direct, reliable comparison
      between tests and between patients. We found that our patients, as a group, were
      affected by a basic activation deficit in attention and by a semantic impairment.
      These deficits in symptom-free patients could indicate that their brains are in
      some ways working differently from those of normal controls and that this pattern
      is not necessarily linked to psychotic symptoms: their neuropsychological
      impairment might reflect a basic difference in the way of processing information
      that is always present and is independent of general intellectual decay.

PMID- 11527352
TI  - Measures of visuospatial short-term memory: the Knox Cube Imitation Test and the
      Corsi Blocks Test compared.
AB  - The present investigation analyzes the characteristics of two tasks that have
      been considered as a measure of visuospatial abilities: The Knox Cube Imitation
      Test and the Corsi Blocks Test. The former was originally devised by Knox (1913)
      to diagnose mental retardation in potential immigrants to the United States,
      while the latter has been specifically designed to be used in neuropsychological
      practice by Corsi (1972). Although both tasks have been widely used in the past,
      there is little empirical research investigating the characteristics of these
      tasks from a theoretical point of view. In order to do so, we carried out two
      parallel experiments in which both tasks were presented in a baseline condition
      as well as in association with three different concurrent tasks (i.e.,
      articulatory suppression, spatial tapping, and random generation) supposed to tap
      the various components of working memory. Results showed that neither of the
      tasks can be considered as a pure measure of visuospatial processing and that, at
      the same time, it is necessary to reconsider the architecture of working memory
      in order to suggest a more integrated functioning of the system.

PMID- 11527353
TI  - Grapheme-phoneme processing of single words.
AB  - Often used in cognitive studies measuring reaction times and in functional
      imaging studies, the subtraction paradigm is based on the comparison of
      performance on tasks presupposed to refer to different cognitive levels of
      processing. Within the framework of the study of phonological processing of
      words, manipulating the grapheme-phoneme transparency of stimuli can represent a
      means of counteracting the methodological drawbacks inherent to the subtraction
      paradigm. Thus, the purpose of this study was to determine the effect of the
      level of difficulty of grapheme-phoneme matching on the processing of transparent
      and nontransparent words. Grapheme-phoneme matching was carried out both on the
      final syllable of words and on sublexical segments within the word. The results
      indicate that processing is faster for the transparent than for the
      nontransparent stimuli. This task will now have to be reintroduced in brain
      imaging studies aiming to look at different levels of difficulty for grapheme
      phoneme matching.

PMID- 11527354
TI  - Transitive gesture production in apraxia: visual and nonvisual sensory
      contributions.
AB  - The production of transitive limb gestures is optimized when the appropriate tool
      can be physically manipulated. Little research has addressed the independent
      contributions of visual and nonvisual sources of sensory information to this
      phenomenon. In this study, 12 control, 37 LHD, and 50 RHD stroke patients
      performed transitive limb gestures to pantomime (to verbal command with the
      object visible) and object manipulation. Performance was more accurate in the
      object manipulation condition, suggesting that haptic and kinesthetic cues are
      important for transitive gesture production. Various patterns of performance were
      observed in the stroke groups, indicating that selective damage to the
      haptic/kinesthetic processing system is possible and common following unilateral
      stroke.

PMID- 11527355
TI  - The validity of cognitive distance in oral and written discourse.
AB  - Oral and written discourse samples of adolescents with closed head injury (CHI)
      and controls were analyzed to determine if efficiency and coherence measures
      changed as the length of their picture descriptions increased. The hypothesis was
      that as ideas were elaborated, the number of words used to express an idea would
      increase and the conceptual connectedness of ideas would decrease. This research
      study supported this expectation for efficiency in normal oral and written
      discourse but not for the discourse of participants with CHI. Further, the
      efficiency measure significantly differentiated the writing and speaking of the
      two groups as the picture descriptions were elaborated. Coherence ratings did not
      distinguish the development of discourse within or between groups

PMID- 11527356
TI  - Task complexity and habituation effects on frontal P300 topography.
AB  - The P3(00) event-related potential (ERP) component is usually reported as having
      a centroparietal maximum. However, the P3 topography is more frontal in early
      session trials which may be masked by averaging over the entire session and is
      evident longer into the test session among elderly subjects. This hyperfrontality
      is interpreted as a sign of poor prefrontal adaptive functioning. In the present
      study, P3 amplitude was examined in university students to determine how early a
      change in amplitude would be evident and the effect of task complexity on the
      amplitude across electrode sites. ERPs were elicited using a working-memory n
      back task where participants pressed a key to target letter presentations in
      three conditions of increasing complexity. Single-trial ERP waveforms were then
      averaged in successive sequences of five trials. Results revealed a greater
      decrease in frontal P3 amplitude compared to the central and parietal P3 after
      the first block of five target trials until the third block. The results are
      interpreted as indicating rapid decrease in hyperfrontality with habituation to
      an easy task. Increases in task complexity (the 2-back paradigm), however,
      reduced this frontal P3 attenuation. Results support a P3 ERP model of
      hyperfrontality reflecting short-term adaptive function by the prefrontal cortex.

PMID- 11527357
TI  - Hemispheric effects of canonical views of category members with known typicality
      levels.
AB  - Is there a preferred hemispheric canonical view of a concept? We investigated
      this question in a natural superordinate category membership decision task using
      a hemifield paradigm. Participants had to decide whether or not an image of an
      object lateralized in the left (LVF) or right (RVF) visual half-field is a member
      of a predesignated superordinate category. The objects represented high, medium,
      or low typicality levels, and each object had six different perspective views
      (front, front-right, front-left, side, back-left, and back-right). The latency
      responses revealed a significant interaction of Hemi Field X View X Typicality
      (there wasno hemifield difference in accuracy). The findings confirm the presence
      of asymmetry in stored concepts in long-term memory and suggest, in addition, a
      hemispheric canonical view of these concepts, a view strongly related to
      typicality level.

PMID- 11527358
TI  - Unilateral neglect: the effect of competing stimuli on estimated line length.
AB  - Normal subjects and patients with right hemisphere lesions with or without signs
      of left unilateral neglect judged the length of a horizontal line presented on
      the left or on the right side of space. In half of the trials, the line was
      presented with a centrally located square or diamond, and subjects had to
      identify the central stimulus before performing the judgment of length. The
      presence of the central stimulus improved accuracy of performance in controls and
      in patients without neglect; neglect patients, however, produced more
      overestimations of left-sided lines when these was presented with a central
      stimulus than when the lines occurred in isolation. This finding underlines the
      importance of attentional factors in length estimates performed by neglect
      patients in their neglected space.

PMID- 11527359
TI  - Planning times during traveling salesman's problem: differences between closed
      head injury and normal subjects.
AB  - We studied planning behavior in a group of normal subjects and a group of closed
      head injury patients (CHI). A computerized version of the traveling salesman's
      problem was used as a visuospatial planning ability task. The program collected
      measurements of partial times, number of moves, and number of skipped subgoals.
      These measures allow us to calculate a "planning index" of subjects' planning
      ability. Results show that CHI patients present limitations in the planning
      process due to the lack of ongoing planning.

PMID- 11527360
TI  - Psychological verbs and the double-dependency hypothesis.
AB  - The double-dependency hypothesis (DDH, Mauner et al., 1993) holds that where two
      dependencies of a certain kind are present, comprehension in Broca's aphasia will
      be random, but that where there is only one dependency, comprehension will be
      intact. We tested this hypothesis by examining the performance of Broca's
      aphasics on sentences with psychological verbs of two different classes. One
      class has an argument structure in which the Experiencer role is assigned to the
      subject. In the other class, the Experiencer role is assigned to the object.
      Subject-Experiencer verbs can form verbal passives which have two relevant
      dependencies, whereas object-Experiencer verbs can form adjectival passives and
      have only one relevant dependency. Thus these sentence types make contrasting
      predictions relevant to the DDH. Our results clearly demonstrate that patients
      understand the adjectival passive psychological verbs, as predicted by the DDH.
      On the verbal passive psychological verbs, patients perform at chance, again
      consistent with DDH predictions. These results firmly buttress the DDH account.
      They also contradict the results of an earlier study (of verbal passive
      psychological verbs only), a study which we argue is plagued with problems
      (namely, Grodzinsky, 1995b).

PMID- 11527361
TI  - The impact of different neuropathologies on pre- and postsurgical
      neuropsychological functioning in children with temporal lobe epilepsy.

PMID- 11527362
TI  - Cognitive and motor development in children with vertically transmitted HIV
      infection.
AB  - This study was designed to examine mental and motor development in infants with
      vertically transmitted human immunodeficiency virus (HIV) infection. Early
      neurodevelopment was examined in 25 young children with HIV infection acquired
      through vertical transmission. Compared with 25 children born to HIV-positive
      mothers but not infected with the virus, and after controlling for developmental
      risk factors, the HIV-infected group showed impairments in mental and motor
      development. Mental and motor development were assessed using the Bayley Scales
      of Infant Development. On the mental scale (MDI), the HIV-infected infants
      obtained significantly lower scores than the uninfected infants. On the
      performace scale (PDI), the HIV-infected infants obtained significantly lower
      standard scores than the uninfected infants. CT scan results were available for
      20 of the HIV-infected children. CT abnormalities were associated with
      developmental delays, particularly for motor development. The results point to
      the importance of early abnormalities in myelination and of subcortical lesions
      of cognitive and motor development.

PMID- 11527363
TI  - Divided attention years after severe closed head injury: the effect of
      dependencies between the subtasks.
AB  - Lesions of white matter which connects distant brain areas are characteristic for
      closed head injury (CHI). It was predicted that this impairs divided attention
      only if dependent subtasks are used which require communication between
      corresponding brain processes. Fourteen chronic severe CHI patients (mean age 42
      years) and 14 healthy controls, matched on age, gender, and education,
      participated in an experiment on divided attention. A typical left hemisphere
      task and a typical right hemisphere task must be simultaneously performed in a
      condition where they are completely independent and in conditions with
      dependencies between the tasks. Only in the dependent conditions the CHI group
      showed poor divided attention performance.

PMID- 11527364
TI  - The left visual hemispace bias for the perception of chimeric faces: a further
      test of the difficulty of discrimination hypothesis.
AB  - When people make judgments of visual-spatial forms, they generally perform better
      if the information is presented in their left visual hemispace (LVH), whereas for
      verbal material, they generally show a right visual hemispace (RVH) bias. For
      verbal material, the strength and direction of the effect also has been linked to
      task difficulty, with the bias shifting toward the RVH as task difficulty
      increases. Two experiments are presented that show the reverse direction of
      change for a nonverbal task; that is, when a nonverbal task is more difficult,
      the usual LVH effect shifts toward an RVH bias. Taking into account recent
      developments in theory and research on hemispheric differences in styles of
      information processing, we propose that task difficulty is related more generally
      to changes in processing style.

PMID- 11527365
TI  - Memory for kinesthetically defined target location: evidence for manual
      asymmetries.
AB  - Sixteen right-handed male adults performed a pointing task without vision. The
      participant's arm was moved passively to one of four targets which was
      subsequently pointed to following a delay of 1, 2, or 10 s. Our previous research
      on visual memory for target location showed a rapid decay which was comparable
      for both hands. The present study of memory for kinesthetic target location found
      decay for the left hand only. These findings suggest two memory stores for target
      location information, one visual which decays over time but is accessible to both
      hands and another based on kinesthetic information which is more stable and limb
      specific.

PMID- 11527366
TI  - Categorical processing in the left and right hemispheres: the effect of category
      repetition.
AB  - Previous research has indicated that the right hemisphere (RH) exhibits priming
      for nonassociated category members, but that the left hemisphere (LH) does not
      (Chiarello et al., 1990; Chiarello & Richards, 1992). Subsequent research has
      shown that time course is an important factor, but what other variables might
      influence the priming of nonassociated semantic category members? We hypothesized
      that repeated stimulation of the same semantic category would produce priming
      within the LH. Previous studies have used few exemplars from a given semantic
      category and thus have not tested this idea. Our prediction was that the LH would
      show priming after an adequate number of category instances had been processed.
      Based on previous research, we predicted no change in the priming observed in the
      RH over trial block. Priming was obtained in the RH, but it diminished as
      category repetition increased. In contrast, priming was not significant in the
      LH, indicating that category repetition does not induce maintenance of category
      members within the LH.

PMID- 11527367
TI  - Word identification in adults with mild mental retardation: does IQ influence
      reading achievement?
AB  - OBJECTIVE: To assess the relationship between word identification and
      intelligence in adults with mild mental retardation (IQ < 80). METHOD: A
      standardized evaluation was administered to 67 adults with mild mental
      retardation. The evaluation included a psychiatric interview, the WAIS-R, and a 2
      h interview with a speech therapist and reading tests. RESULTS: Causes of mental
      retardation were diverse in the sample, and IQ scores ranged from 43 to 79 (mean
      score = 64). All subjects exhibited reading impairment, including 69% with severe
      impairment. No subject with an IQ score under 65 was able to perform adequately
      in the word identification tasks. Word identification was correlated with total
      and verbal IQ, but not with performance IQ. CONCLUSION: Our results suggest that,
      in contrast to subjects with normal intelligence, IQ score is correlated with
      reading in subjects with mild mental retardation. Finally, remediation should be
      preferentially implemented for subjects with IQ score greater than 65.

PMID- 11527368
TI  - The role of prosody in discourse processing.
AB  - The influence of prosody and its visual analog, punctuation, in text
      comprehension was investigated in two experiments. In the first experiment 20
      subjects listened to three taped passages of equal length and difficulty varying
      in intonation (normal, monotonous, or altered) and were tested on tasks of text
      comprehension and word recognition. In the second experiment 20 new subjects read
      the same passages but with varying punctuation (appropriate, no punctuation, or
      altered) and were also tested on text comprehension and word recognition.
      Subjects' reading time was also recorded. ANOVA results revealed that altered
      prosody and punctuation affect performance in a similar fashion and seriously
      impair text comprehension and word recognition. This sensitivity to altered
      intonation suggests that linguistic prosody not only supplies redundant cues for
      judging sentence structure but that it also manages attentional resources to help
      with semantic encoding of lexical units and with the organization of linguistic
      information in long term memory.

PMID- 11527369
TI  - Position of the egocentric reference and performance in line bisection and
      subjective vertical estimation tasks.
AB  - Egocentric body coordinates such as the sagittal midline have been proposed to
      act as a reference for ballistic movements in extracorporeal space. Symmetrical
      functioning of the multiple neural structures processing sensory information
      would account for the normal sagittal position of the egocentric reference.
      According to this hypothesis a unilateral parietal lesion would induce a
      ipsilesional deviation which would prevent neglect patients from responding to
      stimuli that occur on that side. In this line of reasoning, an experimental
      manipulation of the position of the egocentric reference by way of a postural
      perturbation should have an effect on visuospatial tasks performance in normal
      subjects. Seventeen right-handed subjects were submitted in the dark to two
      visuomotor tasks: the adjustment of a luminescent rod to the vertical and the
      bisection of a luminescent line, either with the trunk and the head aligned at 0
      degrees or with a 30 degrees trunk rotation to the right or to the left. Results
      revealed no significant effect of trunk rotation on the performance in both
      tasks. We discuss these findings and their implication for the understanding of
      the neglect syndrome.

PMID- 11527370
TI  - Age vs Alzheimer's: a computational model of changes in representation.
AB  - Previous research has demonstrated that the language of older adults leads to
      denser representations in a high dimensional model of memory than does the
      language of younger adults (Conley & Burgess, in press), and thus that density in
      the model (HAL or the hyperspace analogue to language) may constitute a useful
      metric in comparing memory for younger and older adults. This paper extends the
      previous research by examining the role of density in semantic representations
      that emerged from the language generated by adults with Alzheimer' s and
      comparing the results with age-matched normal controls. We found that, just as
      older adults have denser representations in semantic space than do younger
      adults, adults with Alzheimer's have still denser representations than normal
      older adults. These results support the hypothesis that greater density, normally
      associated in the model with good semantic depth, may in fact reach a "saturation
      point" and affect retrieval in older adults and especially adults with
      Alzheimer's.

PMID- 11527371
TI  - Visuospatial working memory in Turner's syndrome.
AB  - Turner's syndrome is a genetic disorder, specific to women, in which one of the X
      chromosomes is partially or completely deleted. This syndrome is associated with
      physical features such as short stature or failure in primary and secondary
      sexual development, together with a specific pattern of cognitive functions. It
      has been suggested that women affected by Turner's syndrome perform poorly in
      tasks measuring visuospatial abilities and have a verbal IQ significantly higher
      than performance IQ. Although this result has received strong empirical support,
      the nature of the visuospatial deficit is still unclear. Recent studies on
      visuospatial processes have highlighted that the underlying cognitive structure
      is more complex than previously suggested and several dissociations have been
      reported (e.g., visual vs spatial, sequential vs simultaneous, or passive vs
      active processes). In the present study we analyze in detail the characteristics
      of the visuospatial deficit associated with Turner's syndrome by presenting four
      young women with a comprehensive battery of tasks designed to tap all aspects of
      visuospatial working memory. Results confirm that Turner's syndrome is associated
      with a general visuospatial working memory deficit, but the pattern of
      performance of different cases can be different, with a greater emphasis on
      active visuospatial processes. and on either sequential or simultaneous spatial
      processes.

PMID- 11527372
TI  - A longitudinal study of the performance of the elderly and young on the Tower of
      Hanoi puzzle and Rey recall.
AB  - Normal performance on the Tower of Hanoi puzzle by amnesic patients has been
      taken as support for viewing this problem solving task as having a nondeclarative
      memory component. Individuals in each decade of life between the 20s and 80s were
      asked to solve this puzzle four times in four sessions with intersession
      intervals from 1 to 7 days (Davis & Keller, 1998). Participants in their 70s and
      80s were significantly impaired compared to participants in their 20s and 30s.
      The elderly were also significantly impaired on five immediate trials of a 15
      words verbal recall test. Participants were readministered these tests an average
      of 6.6 years later for the elderly (n = 12) and 7.7 years later for the young (n
      = 11). For the Tower of Hanoi, the performance of the elderly, but not the young
      individuals, was significantly poorer than their original performance. For the
      verbal recall test, no significant change over time was detected for the young or
      elderly participants. These findings support the view that some nondeclarative
      and/or problem solving tasks demonstrate as great or greater decline with age
      than some declarative tasks.

PMID- 11527373
TI  - A ten-year longitudinal examination of repetition priming, incidental recall,
      free recall, and recognition in young and elderly.
AB  - The effects of age and time on nondeclarative and declarative memory in young and
      elderly were examined in a 10-year longitudinal study using tests of word-stem
      priming, incidental recall, free recall, and recognition. The elderly were
      significantly impaired on all tests, but no reliable longitudinal decrement by
      the elderly was detected for priming, incidental recall,or recognition. The
      elderly demonstrated a significant longitudinal decline in declarative memory as
      assessed by a test of free recall. While nondeclarative memory declines with age,
      the longitudinal findings are consistent with the view that declarative memory is
      more susceptible to the effects of aging.

PMID- 11527374
TI  - OsK2, a new selective inhibitor of Kv1.2 potassium channels purified from the
      venom of the scorpion Orthochirus scrobiculosus.
AB  - A novel inhibitor of voltage-gated K(+) channels has been purified to homogeneity
      from the venom of the black scorpion Orthochirus scrobiculosus. This toxin, named
      OsK2, has been characterized as a 28-residue peptide, containing six conserved
      cysteine residues and was shown to be a potent and selective blocker of Kv1.2
      channels (K(d) = 97 nM). OsK2 is the second member of the 13th subfamily of short
      chain K(+) channel-blocking peptides known thus far and is therefore called alpha
      KTx 13.2.

PMID- 11527375
TI  - Transient hypoxia differentially decreases GRK2 protein levels in CHO cells
      stably expressing the m1 mAChR.
AB  - G protein-coupled kinase 2 (GRK2) has a key role in regulating signaling
      activities of a variety of G protein-coupled receptors (GPCRs). Several recent
      studies have directly implicated GRK2 phosphorylation in desensitization of
      GPCRs. In addition, binding by G(betagamma) or phosphorylation by PKC or c-Src
      [corrected] has been shown to activate or enhance GRK2 activity, respectively.
      Conversely, the calcium binding protein calmodulin or the serine/threonine kinase
      ERK has been implicated in inhibiting GRK2 activity. However, with the exception
      of a recent report indicating that activation of beta2-adrenergic receptor
      results in the ubiquitination and rapid degradation of GRK2, very little is known
      about cellular mechanisms that alter the protein levels of GRK2 [corrected].
      Here, we report a novel serendipitous observation regarding alteration of GRK2
      [corrected] protein levels. Exposure of CHO cells stably expressing the m1
      muscarinic acetylcholine receptor (mAChR) to transient hypoxia caused near
      ablation of the GRK2 protein. In contrast, GRK2 protein levels remained unchanged
      in the parental CHO cells or in CHO cells stably expressing the m2 mAChR when
      exposed to transient hypoxia. The present study reports a novel observation that
      is unveiled by transient hypoxia in which GRK2 protein levels are altered by
      cellular mechanisms involving the m1 mAChR.

PMID- 11527376
TI  - The effects of AICAR on adipocyte differentiation of 3T3-L1 cells.
AB  - The AMP-activated protein kinase (AMPK) activator, 5-aminoimidazole-4-carboxamide
      ribonucleoside (AICAR), has been found to inhibit the differentiation of 3T3-L1
      adipocytes, if added at an early phase of differentiation. AICAR blocks the
      expression of the late adipogenic markers, fatty acid synthase and acetyl-CoA
      carboxylase, and of the transcription factors, C/EBPalpha and PPARgamma. It also
      inhibits early clonal expansion of pre-adipocytes, prevents the fall in C/EBPbeta
      expression during the intermediate stage of differentiation and inhibits the late
      phase expression of CHOP-10, an antagonist of C/EBPbeta. These data suggest a
      possible inhibitory role for AMPK in the process of adipose differentiation and
      suggest that AMPK might be a target to block adipogenesis.

PMID- 11527377
TI  - Long-term modulation of HERG channel gating in hypoxia.
AB  - Using the patch-clamp technique, we analysed changes in the biophysical
      properties of HERG potassium channels in neuroblastoma cells long-term exposed to
      hypoxia. In this condition, HERG channels underwent a profound modulation that
      consisted of: (i) a slowing in open-close kinetics; (ii) a marked hyperpolarizing
      shift in voltage dependence of steady-state activation; and (iii) a slowing of
      the inactivation removal. The overall physiological impact of these changes in
      neuroblastoma cells is an increase in the HERG window current in the range of the
      resting potential (V(REST)), which varied between -40 and -30 mV. Such a current
      modulation is suitable to stabilise the resting potential (V(REST)) in hypoxic
      environments.

PMID- 11527378
TI  - The genomic structure and promoter region of the human parkin gene.
AB  - Parkin has been identified as a causative gene of the autosomal recessive
      juvenile parkinsonism (AR-JP). In this study, we determined the genomic structure
      of the Parkin gene and identified a core promoter region based on the DNA
      sequence of 1.4 Mb. The 5'-flanking region contained no apparent TATA or CAAT box
      elements but several putative cis-elements for various transcription factors. The
      GC- and CpG-rich regions were observed not only in the 5'-flanking sequence but
      also in the 5'-part of the first intron of Parkin. We identified an exact
      starting point of Parkin transcription. A core promoter region was determined by
      transfecting a series of deletion constructs with a dual luciferase reporter
      system into human neuroblastoma cells. Furthermore, we located a neighboring
      novel gene in a head-to-head direction with Parkin with only a 198-bp interval.

PMID- 11527379
TI  - Differential regulation of IL-1beta and TNF-alpha RNA expression by MEK1
      inhibitor after focal cerebral ischemia in mice.
AB  - Activation of the extracellular-signal-responsive kinase (ERK 1/2) by MAP
      kinase/ERK kinase (MEK1/2) following ischemia/reperfusion in the brain has been
      associated with cell death since inhibition of MEK1/2 provides neuroprotection in
      cerebral ischemia injury. Since inflammation has been implicated in ischemic
      brain injury, the present study investigated whether MEK1/2 modifies expression
      of two key inflammatory cytokines, IL-1beta and TNFalpha, that have been shown to
      exacerbate ischemic brain injury. A mouse model of transient cerebral ischemia
      was deployed to test the effect of selective MEK1/2 inhibitor (SL327) on infarct
      size and cytokine expression. SL327 (100 mg/kg, i.p.) administered 15 min prior
      to ischemia resulted in 64% reduction in infarct size over controls (n = 8, P <
      0.01). Under the same condition, SL327 significantly reduced peak expression of
      IL-1beta mRNA (59% reduction compared to vehicle, P < 0.01, n = 4) but not TNF
      alpha mRNA. A parallel reduction in IL-1beta protein (67%, P < 0.05, n = 6) was
      also observed using ELISA analysis. These data suggest that the neuroprotective
      effect of MEK1/2 inhibition may be mediated by suppression of IL-1beta. The study
      also demonstrates for the first time that these two cytokines are differentially
      regulated by kinase mediated signaling pathways.

PMID- 11527380
TI  - Intrinsic fluorescence from DNA can be enhanced by metallic particles.
AB  - High sensitivity detection of DNA is essential for genomics. The intrinsic
      fluorescence from DNA is very weak and almost all methods for detecting DNA rely
      on the use of extrinsic fluorescent probes. We show that the intrinsic emission
      from DNA can be enhanced many-fold by spatial proximity to silver island films.
      Silver islands are subwavelength size patches of metallic silver on an inert
      substrate. Time-resolved measurements show a decreased lifetime for the intrinsic
      DNA emission near the silver islands. These results of increased intensity and
      decreased lifetime indicate a metal-induced increase in the radiative rate decay
      of the DNA bases. The possibility of increased radiative decay rates for DNA
      bases and other fluorophores suggest a wide variety of DNA measurements and other
      biomedical assays based on metal-induced increases in the fluorescence quantum
      yield of weakly fluorescent substances.

PMID- 11527381
TI  - Analysis of the mammalian talin2 gene TLN2.
AB  - We have utilised genomic and EST databases to assemble the sequence of the human
      talin2 (TLN2) gene. Talin2 protein is similar in size and sequence to talin1
      throughout its length (74% identity, 86% similarity). The major differences are
      in (i) the size of the genes, the TLN2 gene is >200 kb compared with
      approximately 30 kb for TLN1 due to a difference in intron size, although
      intron/exon boundaries, with the exception of two, are strictly conserved; (ii)
      the expression patterns, TLN1 gives rise to an approximately 8-kb mRNA which is
      observed in all tissues, whereas TLN2 gives rise to multiple transcripts with the
      highest levels in heart.

PMID- 11527382
TI  - Through induction of juxtaposition and tyrosine kinase activity of Jak1, X-gene
      product of hepatitis B virus stimulates Ras and the transcriptional activation
      through AP-1, NF-kappaB, and SRE enhancers.
AB  - Here, based on the recent finding of HBx (X-gene product of hepatitis B virus) as
      the inducer of Jak1, we investigated the mechanism for the HBx-mediated host cell
      regulation and found that (i) HBx associates specifically with Jak1 in vivo; (ii)
      HBx itself forms a dimer which leads to juxtaposition of associated Jak1 and
      subsequent activation of the tyrosine kinase activity of Jak1; (iii) HBx-mediated
      activation of the promoters containing AP-1-, NF-kappaB-, SRE-, and SIE-sites is
      dependent on the activation of Jak1; (iv) Jak1, once activated by HBx, induces
      Ras activity through recruitment of Grb2 and induces tyrosine phosphorylation of
      Raf1, but not shc. These findings show that previously reported functions of HBx,
      such as activation of multiple signaling pathways and transcriptional activation
      are attributable to HBx-mediated Jak1 activation.

PMID- 11527383
TI  - Type A allatostatins from Drosophila melanogaster and Diplotera puncata activate
      two Drosophila allatostatin receptors, DAR-1 and DAR-2, expressed in CHO cells.
AB  - The type-A allatostatins A (AST-A) are a group of insect peptides with a common C
      terminal motif Y/FXFGL-NH(2). The existence of at least four putative type A
      Drosophila melanogaster ASTs (called type A drostatins or DST-As) has been
      predicted from the sequence of a recently cloned DST-A preprohormone [C. Lenz et
      al. (2000) Biochem. Biophys. Res. Commun. 273, 126-1131]. SRPYSFGL-NH(2), (DST
      3A), the only DST isolated from Drosophila so far, activated the first cloned DST
      A GPCR (DAR-1) [N. Birgul et al. (1999) EMBO J. 18, 5892-5900]. A newly cloned
      orphan Dm GPCR, which shares 47% overall and 60% transmembrane region sequence
      identity with DAR-1, was classified as a second putative Dm DST-A receptor (DAR
      2) [C. Lenz et al. (2000) Biochem. Biophys. Res. Commun. 273, 571-577]. Although
      activation of DAR-2 by DSTs has been postulated, no experimental evidence for
      that has been presented to date. In this study, we expressed both DAR-1 and DAR-2
      in CHO cells and used a GTPgammaS and a Ca(2+) mobilization assay for
      pharmacological evaluation of the receptors. Synthetically prepared DST-As, as
      well as selected Diplotera punctata (cockroach) ASTs, activated DAR-1 and DAR-2
      in both functional assays indicating ligand redundancy and cross species
      activity. Cell pretreatment with pertussis toxin led to some differences in the
      nature and magnitude of signaling pathways at the DAR-1 and DAR-2 receptors,
      suggesting possible differential coupling to cellular effector system(s) and
      distinct biological functions of each receptor in vivo.

PMID- 11527384
TI  - CueO is a multi-copper oxidase that confers copper tolerance in Escherichia coli.
AB  - The putative multi-copper oxidase CueO had previously been implicated in
      intrinsic copper resistance in Escherichia coli. In this report we showed that
      the presence of CueO in the periplasm protected alkaline phosphatase from copper
      induced damage. CueO contained four copper atoms per molecule and displayed
      spectroscopic properties typical of blue copper oxidases. CueO catalyzed the
      oxidation of p-phenylenediamine (pPD), 2,6-dimethoxyphenol (DMP) and exhibited
      ferroxidase activity in vitro.

PMID- 11527385
TI  - IGF-I and mechanical environment interact to modulate engineered cartilage
      development.
AB  - Bovine calf articular chondrocytes were seeded onto biodegradable polyglycolic
      acid scaffolds and cultured for four weeks using in vitro systems providing
      different mechanical environments (static and mixed Petri dishes, static and
      mixed flasks, and rotating vessels) and different biochemical environments
      (medium with and without supplemental insulin-like growth factor I, IGF-I). Under
      all conditions, the resulting engineered tissue histologically resembled
      cartilage and contained its major constituents: glycosaminoglycans, collagen, and
      cells. The mechanical environment and supplemental IGF-I (a) independently
      modulated tissue morphology, growth, biochemical composition, and mechanical
      properties (equilibrium modulus) of engineered cartilage as previously reported;
      (b) interacted additively or in some cases nonadditively producing results not
      suggested by the independent responses, and (c) in combination produced tissue
      superior to that obtained by modifying these factors individually.

PMID- 11527386
TI  - Troglitazone inhibits growth of MCF-7 breast carcinoma cells by targeting G1 cell
      cycle regulators.
AB  - Peroxisome proliferator activated receptor gamma (PPARgamma) is a member of the
      nuclear receptor superfamily. Ligand activation of PPARgamma has been shown to
      cause growth arrest in several human tumor cell types, but the underlying
      molecular mechanism has not been elucidated. We report here that the PPARgamma
      ligand troglitazone (TRO) inhibited MCF-7 cell proliferation by blocking events
      critical for G1 --> S progression. Flow cytometry demonstrated that TRO at 20
      microM increased the percentage of cells in G1 from 51 to 69% after 24 h.
      Accumulation of cells in G1 was accompanied by an attenuation of Rb protein
      phosphorylation associated with decreased CDK4 and CDK2 activities. Inhibition of
      CDK activity by TRO correlates with decreased protein levels for several G1
      regulators of Rb phosphorylation (cyclin D1, and CDKs 2, 4, and 6).
      Overexpression of cyclin D1 partially rescued MCF-7 cells from TRO-mediated G1
      arrest. Targeting of G1 regulatory proteins, particularly cyclin D1, and the
      resulting induction of G1 arrest by TRO may provide a novel antiproliferative
      therapy for human breast cancer.

PMID- 11527387
TI  - PGE(2) stimulates VEGF expression in endothelial cells via ERK2/JNK1 signaling
      pathways.
AB  - Vascular endothelial growth factor (VEGF) plays an essential role in the
      initiation and regulation of angiogenesis-a crucial component of wound healing
      and cancer growth. Prostaglandins (PGs) stimulate angiogenesis but the precise
      mechanisms of their pro-angiogenic actions remain unexplained. We investigated
      whether prostaglandin E(2) (PGE(2)) can induce VEGF expression in rat gastric
      microvascular endothelial cells (RGMEC) and the signaling pathway(s) involved. We
      demonstrated that PGE(2) significantly increased ERK2 and JNK1 activation and
      VEGF mRNA and protein expression. Incubation of RGMEC with PD 98059 (MEK kinase
      inhibitor) significantly reduced PGE(2)-induced ERK2 activity, VEGF mRNA and
      protein expression. Furthermore, PD 98059 treatment almost completely abolished
      JNK1 activation. Our data suggest that PGE(2)-stimulates VEGF expression in RGMEC
      via transactivation of JNK1 by ERK2. One potential implication of this finding is
      that increased PG levels in cancers could facilitate tumor growth by stimulating
      VEGF synthesis and angiogenesis.

PMID- 11527388
TI  - Efficient retroviral gene transfer to the liver in vivo using nonpolypeptidic
      mitogens.
AB  - Recombinant retroviral vectors are attractive tools for achieving sustained
      expression of a therapeutic gene in the liver. However, cell division is required
      for efficient transduction with these vectors. Here we report that two widely
      used liver mitogens, triiodothyronin (T3) and cyproterone acetate (CPA), enable
      hepatocyte transduction with recombinant retroviral vectors delivered in vivo
      into the bloodstream. Treatment with T3 as well as CPA, alone or in combination,
      resulted in an increase in hepatocyte replication predominantly around the portal
      tract. The mitogenic activity made it possible to transduce hepatocytes in the
      same location. Moreover, when administered together, the two drugs synergized and
      the transduction level reached 5% of hepatocytes. This transduction level is
      compatible with clinical applications for a number of inherited liver diseases.
      Since these two compounds have a long history of safe clinical use, we propose
      that these liver mitogens may have potential for clinical application in liver
      directed gene therapy.

PMID- 11527389
TI  - Characterization of loops of the yeast mitochondrial ADP/ATP carrier facing the
      cytosol by site-directed mutagenesis.
AB  - To characterize structural features of the regions of the yeast type 2 ADP/ATP
      carrier (yAAC2) facing the cytosol, we prepared its Cys-less mutant, in which all
      four cysteine residues were replaced by alanine residues. The Cys-less mutant
      functioned like native yAAC2, showing that the cysteine residues are not
      essential. We then prepared cysteine mutants by substituting Ser(21) in the
      putative N-terminal region, Ala(124) and Ser(222) in the first and second loops
      facing cytosol, respectively, and Leu(312) in the C-terminal region of the Cys
      less mutant for cysteine and examined the labeling of the substituted cysteine
      residues of the mutants with the membrane-impermeable SH reagent eosin-5
      maleimide (EMA) from the cytosol. EMA labeled all the mutants, showing that all
      regions containing mutated residues faced the cytosolic side. The effects of
      transport inhibitors on EMA labeling were also examined. From the results, the
      location and conformation of the region around mutated residues were discussed.

PMID- 11527390
TI  - Evidence against GRB10 as the gene responsible for Silver-Russell syndrome.
AB  - Recent evidence shows that Silver-Russell syndrome (SRS), the major functional
      deficit of which is limited growth, both intrauterine and postnatal, is due to a
      double dose of a gene within 7p11.2-p13 that is normally expressed exclusively
      from the maternal copy. Of the several growth-related genes in this chromosomal
      region, only GRB10 has been demonstrated to be imprinted; however, imprinting was
      limited to brain and muscle and was incomplete. Using reverse-transcript PCR, we
      now confirm GRB10 imprinting in these two tissues is isoform-specific and, more
      importantly, demonstrate absence of imprinting in growth plate cartilage, the
      tissue most directly involved in linear growth. Thus, it is unlikely that GRB10
      is the gene responsible for SRS.

PMID- 11527391
TI  - Interaction between ATBP and DmUbc9 in the expression of the Sarcophaga lectin
      gene.
AB  - We previously demonstrated that (A+T)-stretch binding protein (ATBP) and Dorsal
      related immunity factor (Dif) are required for the expression of the Sarcophaga
      lectin gene in SL-2 cells (Aozasa et al., Eur. J. Biochem. 268, 2506-2511, 2001).
      The present study demonstrates that DmUbc9 interacts with ATBP, and
      cotransfection of the DmUbc9 vector with ATBP and Dif vectors greatly enhances
      the expression of the luciferase reporter of the Sarcophaga lectin gene in SL-2
      cells. These results suggest that sumoylation of ATBP is involved in the
      expression of the Sarcophaga lectin gene in this system.

PMID- 11527392
TI  - Transient suppression of X-ray-induced apoptosis by exposure to power frequency
      magnetic fields in MCF-7 cells.
AB  - Epidemiological studies suggest that exposure to power frequency magnetic fields
      may be a risk factor for breast cancer in humans. To study the relationship
      between exposure to 60-Hz magnetic fields (MFs) and breast cancer, cell cycle
      distribution, apoptosis, and the expression of related proteins (p21, Bax, and
      Bcl-2) were determined in MCF-7 cells following exposure to magnetic fields (60
      Hz, 5 mT) alone or in combination with X rays. It was found that exposure of MCF
      7 cells to 60-Hz MFs for 4, 8, and 24 h had no effect on cell cycle distribution.
      Furthermore, 60-Hz MFs failed to affect cell growth arrest and p21 expression
      induced by X rays (4 Gy). Similarly, 60-Hz MFs did not induce apoptosis or the
      expression of Bax and Bcl-2, two proteins related to apoptosis. However, exposure
      of cells to 60-Hz MFs for 24 h after irradiation by X rays (12 Gy) significantly
      decreased apoptosis and Bax expression but increased Bcl-2 expression. The
      effects of exposure to 60-Hz MFs on X-ray-induced apoptosis and Bax and Bcl-2
      expressions were not observed at 72 h. These data suggest that exposure to 60-Hz
      MFs has no effects on the growth of MCF-7 cells, but it might transiently
      suppress X-ray-induced apoptosis through increasing the Bcl-2/Bax ratio.

PMID- 11527393
TI  - Metastin suppresses the motility and growth of CHO cells transfected with its
      receptor.
AB  - We recently reported having identified of the ligand for an orphan G-protein
      coupled receptor, hOT7T175, as the gene product (68-121)-amide of the metastasis
      suppressor gene KiSS-1. We further showed that the ligand, which we named
      "metastin," inhibits chemotaxis and invasion of Chinese hamster ovary (CHO) cells
      transfected with hOT7T175 cDNA (CHO/h175) in vitro, and pulmonary metastasis of
      hOT7T175-transfected B16-BL6 melanomas in vivo. In the present study, we
      investigated the activity of metastin in CHO/h175 cells in greater detail.
      Metastin significantly suppressed motility in a chemotaxis assay and wound
      healing assay at 10-100 nM order concentrations. Two N-terminally truncated
      peptides, metastin(40-54) and metastin(45-54) inhibited the migration of CHO/h175
      cells as potently as metastin itself. Metastin also inhibited the spreading,
      monolayer growth and colony formation in agar (0.8%) of CHO/h175 cells at 10-100
      nM concentrations. These results indicate that metastin is a potent inhibitor of
      cell motility, leading to suppression of cell growth and antimetastatic activity,
      and suggest that low molecular chemical compounds could replace its activity as a
      novel antimetastatic agent.

PMID- 11527394
TI  - Altered sensitivity to a novel vasoconstrictor endothelin-1 (1-31) in myometrium
      and umbilical artery of women with severe preeclampsia.
AB  - We have suggested that a novel endothelin-1 with 31 amino acids [ET-1 (1-31)]
      plays an important role in fetal circulation, owing to a strong contractile
      activity on the umbilical artery. To clarify the pathophysiological significance
      of ET-1 (1-31) in the development of severe preeclampsia, its contractile
      activities on human umbilical arteries and uterine smooth muscle from patients
      with preeclampsia were studied. The contraction by ET-1 (1-31) was stronger in
      uterine smooth muscle of the patients with severe preeclampsia than that of
      normal subjects. On the contrary, the constriction of umbilical artery of the
      patients with eclampsia was significantly weaker than that of normal pregnant
      women. The stronger contraction of myometrium by ET-1 (1-31) in patients with
      severe preeclampsia observed for the first time in the present study suggests
      that ET-1 (1-31) might be involved in the development of preeclampsia.

PMID- 11527395
TI  - The effect of endothelin-1 on nuclear factor kappa B in macrophages.
AB  - Nuclear factor kappaB (NF-kappaB) is a transcriptional factor which may be
      pivotal in the pathogenesis of atherosclerosis. Endothelin-1 (ET-1) is a peptide
      with proatherogenic properties. We hypothesized that ET-1 may act through
      activation of NF-kappaB and degradation of IkappaB-alpha, the cytosolic inhibitor
      of NF-kappaB activation, to create an atherogenic environment. The human
      monocytic cell line THP-1 was stimulated with ET-1 +/- the ET antagonist, BQ788
      and the proteosome inhibitor, PSI. LPS was used as a positive control. Gel shift
      assays for NF-kappaB activity and Western blot analysis for IkappaB-alpha were
      performed. Both LPS and ET-1 led to activation of NF-kappaB in nuclear extracts
      [3.4 +/- 0.45 (LPS) and 2.9 +/- 0.26 (ET-1) fold increase in Arbitrary
      Densitometric Units (ADU) compared with negative control (P < 0.005 in both
      cases)]. In the presence of the ETB antagonist, BQ788, NF-kappaB activation was
      attenuated and not different from control (1.7 +/- 0.24 fold DU compared with
      negative control; P = NS). In addition, both LPS and ET-1 mediated NF-kappaB
      activation were attenuated by preincubation with the proteosome inhibitor, PSI
      (1.3 +/- 0.58 and 1.1 +/- 0.3 fold increase in ADU compared with negative control
      respectively). Both LPS and ET-1 led to a decrease in the amount of IkappaB-alpha
      present in the THP-1 cytoplasmic extracts (2.1 +/- 1.5% and 54 +/- 15.7% of ADU
      vs negative control (P < 0.05). NF-kappaB is activated by ET-1 in human THP-1
      monocytes. This data supports a role for the ETs in the development of
      inflammation in the vessel wall in atherosclerosis.

PMID- 11527396
TI  - Molecular cloning and characterization of a novel Jasmonate inducible
      pathogenesis-related class 10 protein gene, JIOsPR10, from rice (Oryza sativa L.)
      seedling leaves.
AB  - A novel rice (Oryza sativa L.) gene, homologous to a sorghum pathogenesis-related
      class 10 protein gene, was cloned from a cDNA library prepared from 2-week-old
      jasmonic acid-treated rice seedling leaves, and named as JIOsPR10 (jasmonate
      inducible). JIOsPR10 encoded a 160-amino-acid polypeptide with a predicted
      molecular mass of 17,173.23 Da and a pI of 5.84. JIOsPR10 was highly similar
      (77%) to the sorghum PR10 protein, but showed less than 55% similarity with other
      identified PR10s at the amino acid level. Genomic Southern analyses indicated the
      presence of related genes in the rice genome. The JIOsPR10 transcript was not
      detected in the healthy leaves, and was not induced after cut. Further expression
      analysis revealed that the signaling components of defense/stress pathways,
      jasmonate, salicylate, and H(2)O(2) significantly up-regulated the JIOsPR10 mRNA
      over the cut control, whereas two other stress regulators, ethylene and abscisic
      acid, failed to induce its expression. Interestingly the protein phosphatase (PP)
      inhibitors, cantharidin, endothall, and okadaic acid, rapidly and potently up
      regulated the JIOsPR10 expression, suggesting involvement of the
      phosphorylation/dephosphorylation events. Additionally, the inducible expression
      of the JIOsPR10 gene was influenced by light signal(s). Finally, the blast
      pathogen (Magnaporthe grisea) also specifically elicited the accumulation of
      JIOsPR10 mRNA in leaves. Induction of the JIOsPR10 gene expression by signaling
      molecules, PP inhibitors and pathogen attack, strongly indicate a role for this
      novel gene in rice self-defense/stress response(s).

PMID- 11527397
TI  - 14-3-3 protein-activated and autoinhibited forms of plasma membrane H(+)-ATPase.
AB  - Several authors previously showed that the interaction between 14-3-3 proteins
      and plasma membrane H(+)-ATPase leads to an activated complex in which the enzyme
      is endowed with more favorable kinetic parameters and a more physiological pH
      optimum. In this paper we report immunological studies with antibodies covering a
      different specific region of the protein, including the N- and the C-terminal
      ends. The results showed that, beside a free and a complexed form, a third form
      of H(+)-ATPase in the cell must exist with low activity and no more activation
      due to the loss of a part of the C-terminal regulatory domain. A model in which
      14-3-3 proteins activate H(+)-ATPase by protecting it from a specific proteolytic
      attack is presented and its generalization is discussed.

PMID- 11527398
TI  - Oxidation and generation of hydrogen peroxide by thiol compounds in commonly used
      cell culture media.
AB  - Many studies have examined the effects of thiol compounds upon cells in culture
      (e.g., upon signal transduction and regulation of gene expression), but few have
      considered how thiols can interact with cell culture media. A wide range of
      thiols (cysteine, GSH, N-acetylcysteine, gamma-glutamylcysteine,
      cysteinylglycine, cysteamine, homocysteine) were found to interact with three
      commonly used cell culture media (RPMI, MEM, DMEM) to generate hydrogen peroxide
      with complex concentration-dependencies. Thiols added to these media rapidly
      disappeared, although less H(2)O(2) was generated on a molar basis than the
      amount of thiol lost. Studies on cellular effects of thiols, especially those on
      redox regulation of gene expression or protein function, need to take into
      account that thiols are rapidly lost, and that their oxidation generates
      H(2)O(2), which can have multiple concentration-dependent effects on cell
      metabolism.

PMID- 11527399
TI  - Role of G proteins and modulation of p38 MAPK activation in the protection by
      nitric oxide against ischemia-reoxygenation injury.
AB  - Protein kinase C (PKC)-mediated regulation of the mitogen-activated protein
      kinases (MAPK) may play a role in the protection afforded by ischemic
      preconditioning (PC). Nitric oxide (NO) can influence MAPK activation via
      interaction with PKC or farnesylation of low-molecular-weight (LMWT) G proteins.
      However, we have recently reported the mechanism of NO-induced cardioprotection
      to be a PKC-independent process. Therefore, we investigated the role of LMWT G
      proteins and MAPK signaling in NO-induced cardioprotection against simulated
      ischemia-reoxygenation (SI-R) injury. Neonatal rat cardiomyocytes treated for 90
      min with the NO donor S-nitroso-N-acetyl-l,l-penicillamine (SNAP) 1 mM were
      protected against 6 h of SI (hypoxic conditions at 37 degrees C with 20 mM
      lactate, 16 mM KCl at pH 6.2) and 24 h reoxygenation under normal culture
      conditions. NO-induced protection was blocked by the G protein inhibitor alpha
      hydroxyfarnesylphosphonic acid (alphaHFP) 10 microM. We studied the time course
      of p42/44 and p38 MAPK dual-phosphorylation hourly during SI using phospho
      specific antibodies. p38 was phosphorylated during SI and the peak
      phosphorylation was significantly delayed by SNAP pretreatment. The p38 inhibitor
      SB203580 1 microM, given during SI, protected against injury. Thus the delay in
      peak p38 activation may contribute to, rather than be the effect of, NO-induced
      cardioprotection. We have shown that p38beta does not contribute to the total p38
      signal in our extracts. Thus there is no detectable beta isoform. We conclude
      that the main isoform present in these cells and thought to be responsible for
      the observed phenomenon, is the alpha isoform.

PMID- 11527400
TI  - Isolation of Bcl-2 binding proteins that exhibit homology with BAG-1 and
      suppressor of death domains protein.
AB  - The Bcl-2 oncoprotein is a potent inhibitor of apoptosis and is overexpressed in
      a variety of different malignancies. Bcl-2 function is regulated through
      heterodimerization with other members of the Bcl-2 protein family. In addition,
      several proteins that are not members of the Bcl-2 family can bind to Bcl-2,
      including BAG-1 protein. In this study, we screened for proteins that bind to Bcl
      2, and isolated two additional members of the BAG-1 protein family, BAG-3 and BAG
      4. The BAG-4 protein that we cloned also corresponds to the recently isolated
      suppressor of death domains (SODD) protein, a molecule that binds and inhibits
      signaling by tumor necrosis factor receptor 1 (TNFR1). Both BAG-3 and BAG-4/SODD
      were found to physically associate with Bcl-2, and both proteins are well
      conserved from human to mouse. A region of homology, comprising 68 amino acids,
      is present in the carboxyl termini of BAG-3 and BAG-4/SODD, and this region
      corresponds with sequences termed BAG domains that are found in other members of
      the BAG-1 protein family. In BAG-3 and BAG-4/SODD, the BAG domains appear to
      constitute the Bcl-2 binding regions of these molecules. BAG-3 and BAG-4/SODD,
      like BAG-1, were also shown to bind to Hsp70 inside the cell. Moreover, BAG-3
      overexpression modestly inhibited apoptosis resulting from cytokine deprivation
      of IL-3-dependent 32D cells. Together, our findings demonstrate that other
      members of the BAG-1 protein family, namely BAG-3 and BAG-4/SODD, bind to Bcl-2
      and provide a potential link between pathways regulated by Bcl-2 and pathways
      regulated by Hsp70, as well as TNFR1.

PMID- 11527401
TI  - MEK1/2 inhibitors promote Ara-C-induced apoptosis but not loss of Deltapsi(m) in
      HL-60 cells.
AB  - The effects of pharmacologic MEK1/2 inhibitors on ara-C-mediated mitochondrial
      injury, caspase activation, and apoptosis have been examined in HL-60 leukemic
      cells. Coadministration of subtoxic concentrations of the MEK1/2 inhibitors U0126
      (20 microM), PD98059 (40 microM), or PD184352 (10 microM) with 10-100 microM ara
      C (6 h) potentiated apoptosis (i.e., by approx twofold), and pro-caspase 3, pro
      caspase 8, Bid, and PARP cleavage. Unexpectedly, MEK1/2 inhibitors failed to
      enhance ara-C-mediated loss of mitochondrial membrane potential (DeltaPsi(m)),
      but instead induced substantial increases in cytosolic release of cytochrome c
      and Smac/DIABLO. U0126/ara-C-mediated apoptosis and pro-caspase 3 activation, but
      not cytochrome c or Smac/DIABLO release, were blocked by the pan-caspase
      inhibitor ZVAD-fmk. Together, these findings indicate that potentiation of ara-C
      mediated lethality in HL-60 cells by MEK1/2 inhibitors involves enhanced
      cytosolic release of cytochrome c and Smac/DIABLO but not discharge of
      DeltaPsi(m), implicating activation of an apoptotic pathway that differs, at
      least with respect to the nature of the accompanying mitochondrial injury, from
      that triggered by ara-C alone.

PMID- 11527402
TI  - Cloning, structure, and expression of the mouse Ovca1 gene.
AB  - We report the isolation of the mouse Ovca1 gene, the orthologue of human
      OVCA1/DPH2L1, a putative tumor suppressor associated with ovarian cancer. Mouse
      Ovca1 contains at least 13 exons and spans approximately 17 kb. Northern analysis
      showed that Ovca1 is expressed in most adult mouse tissues. The most predominant
      Ovca1 transcript is 2.1 kb. RT-PCR analysis demonstrated Ovca1 expression in
      embryos from 8.5 days postcoitum (d.p.c.) to 10.5 d.p.c., and various organs of
      14.5 d.p.c. embryos. Mouse Ovca1 encodes a protein of 438 amino acids and has
      high identity with human OVCA1. Western blot and immunohistochemistry revealed
      that mouse OVCA1 is a 50-kDa protein that is predominately localized in a
      punctate pattern in the nucleus. Based on gene homology, structure, and
      expression patterns, these findings indicate that mouse Ovca1 is the orthologue
      of human OVCA1/DPH2L1. This study will facilitate experiments to elucidate the in
      vivo role of Ovca1 in cancer.

PMID- 11527403
TI  - Apoptosis induced by human Fas-associated factor 1, hFAF1, requires its ubiquitin
      homologous domain, but not the Fas-binding domain.
AB  - FAF1 is a Fas-binding protein without typical death domain. Instead, FAF1 has
      several domains found in proteins of ubiquitination pathway. Transient
      overexpression of hFAF1 in BOSC23 cells caused membrane blebbing and cell body
      condensation which were characteristics of apoptosis. Subsequent analysis
      revealed that overexpression of hFAF1 induced nuclear condensation, appearance of
      phosphatidylserines in the outer leaflet of the cellular membrane, and caspase 3
      activation. The apoptotic potential of hFAF1 required downstream ubiquitin
      homologous domain (UB2) and adjacent nuclear localization signal but not the Fas
      binding domain. Our data showed that mere intrinsic overexpression of hFAF1
      initiated apoptosis in the absence of any extrinsic death signal in BOSC23 cells.

PMID- 11527404
TI  - FUP1, a gene associated with hepatocellular carcinoma, stimulates NIH3T3 cell
      proliferation and tumor formation in nude mice.
AB  - Human primary hepatocellular carcinoma (HCC)is one of the highly prevalent
      malignant diseases worldwide, the identification of HCC-associated genes has been
      a major approach in elucidating the molecular mechanism of tumorigenesis of HCC.
      In our previous studies, a function-unknown gene, which displayed marked
      expression difference between the HCC sample and normal liver control has been
      detected by cDNA microarray. This gene was named after fup1 (function-unknown
      protein 1), and was cloned according to the data of GenBank. The cDNA of fup1 has
      an open-reading frame 1233 base pairs in size. Here, the function analysis of
      FUP1 related to HCC is being reported. The NIH3T3 cells transiently transfected
      with FLAG-conjugated FUP1 revealed strong nuclear staining in immunofluorescent
      assay. Furthermore, cell proliferation enhancing activity of fup1 was shown by
      MTT assay in stable transfectant NIH3T3 cell line with pcDNA3-derived plasmid
      having fup1 under the regulation of pCMV, while cell proliferation repressing
      activity of antisense fup1 was observed in BEL7404 stable transfectant cells.
      Tumorigenicity of the above stable transfectant cells was analyzed in nude mice
      compared with appropriate controls. The result was in good agreement with MTT
      assay. Elevated tumorigenicity of fup1 transfected NIH3T3 cell and repressed
      tumorigenicity of antisense fup1 transfected BEL7404 cell were clearly
      demonstrated. The results above suggested that fup1 might be a critical gene
      related to carcinogenesis of HCC. Detailed molecular function of fup1 remains to
      be elucidated.

PMID- 11527405
TI  - An anti-EGF monoclonal antibody that detects intramolecular communication in
      factor IX.
AB  - Coagulation factor IX contains a gamma-carboxyglutamic acid (Gla) module, two
      epidermal growth factor-like (EGF) modules, and a serine protease region. We have
      characterized a mouse monoclonal antibody that binds the N-terminal EGF-like
      module of human factor IX with high affinity. Studies of recombinant factor IX
      mutants indicated that the epitope is located in the C-terminal end of the EGF
      like module, which is consistent with the binding being non-Ca(2+)-dependent. The
      antibody bound factor IXa (K(D) = 7.6 x 10(-10) M) with about 10-fold higher
      affinity than factor IX (K(D) = 6.2 x 10(-9) M). Binding of the antibody to
      factor IXa did not affect the amidolytic activity of the protein, nor was binding
      affected by active site inhibition of factor IXa. These results are consistent
      with long-range interactions between the serine protease region and the N
      terminal EGF-like module in factor IX.

PMID- 11527406
TI  - ik3-1/Cables is associated with Trap and Pctaire2.
AB  - ik3-1/Cables is associated with and phosphorylated by cdk3 in self-replicating
      cells. In postmitotic neurons, it may serve as an adaptor molecule, functionally
      connecting c-abl and cdk5, and supporting neurite growth. Here, we cloned cDNAs
      coding for mouse Trap (tudor repeat associator with Pctaire 2) to interact with
      ik3-1. ik3-1 interacts with a region of mouse Trap containing the C-terminal
      tudor repeat domains 4 and 5 (corresponding to amino acids 881-1086 of mouse
      Trap). Furthermore, the N-terminal 93-amino-acid domain of ik3-1 is essential for
      ik3-1 interaction with Trap. Moreover, ik3-1 is coimmunoprecipitated with Pctaire
      2 from COS7 cells, although we could not clarify whether ik3-1 is directly
      associated with Pctaire 2 or indirectly associated with Pctaire 2 through Trap.
      In vitro kinase assay indicated that ik3-1 does not activate phosphorylation of
      myelin basic protein or histione H 1 by the Pctaire 2-mediated kinase. These
      findings led us to speculate that through ik3-1, the Pctaire family and Trap may
      be functionally connected with cdk3 or cdk5.

PMID- 11527407
TI  - A factor of inducing IgE from a filarial parasite prevents insulin-dependent
      diabetes mellitus in nonobese diabetic mice.
AB  - Parasitic helminth infections are characterized by eosinophilia and markedly
      elevated levels of circulating antigen-nonspecific immunoglobulin E (IgE),
      responses from which concern helminth protection. We previously purified a factor
      from Dirofilaria immitis that induces antigen-nonspecific IgE in mice and rats.
      Recombinant DiAg (rDiAg) has various biological activities. It is also known that
      parasitic helminth infection generates tremendous Th2 responses. The nonobese
      diabetic (NOD) mouse spontaneously develops Th1 cell-dependent autoimmune
      diabetes. Here we investigated the effects of rDiAg on the initiation and
      progression of this disease. rDiAg treatment of 6-week-old NOD females (the age
      at which insulitis typically begins) completely prevented insulitis and diabetes.
      Thus, rDiAg impaired the islet Ag-specific Th1 cell response in vivo, and the
      prevention of diabetes by rDiAg was associated with switching of the response
      from a Th1 to a Th2 profile. Since rDiAg clearly prevented insulitis by
      inhibiting the development and further accumulation of pathogenic Th1 cells to
      islets of Langerhans, we conclude that DiAg is a native Th2 inducer in filarial
      helminth and that Th1 responses are required for early events in the development
      of spontaneous autoimmune diabetes. In conclusion, the presence of parasitic
      helminth infections may play an important role as an immunomodulator in some
      autoimmune diseases or allergies.

PMID- 11527408
TI  - Hepatic stellate cells contain the functional estrogen receptor beta but not the
      estrogen receptor alpha in male and female rats.
AB  - In an earlier study, we showed that estradiol (E2) inhibits proliferation and
      transformation in cultured rat hepatic stellate cells (HSCs) and that the actions
      of E2 are mediated through estrogen receptors (ERs). This study reports on an
      investigation of the cellular localization of ER subtypes ERalpha and ERbeta
      using immunohistochemistry in experimental fibrotic liver rats and of each ER
      subtype expression in cultured rat HSCs by evaluating the produced mRNA and
      protein. The results indicate that high levels of ERbeta expression and low or no
      levels of ERalpha expression were observed in normal and fibrotic livers and in
      quiescent and activated HSCs from both males and females. The specificity of E2
      mediated antiapoptotic induction through the ERbeta was shown by dose-dependent
      inhibition by the pure ER antagonist ICI 182,780 in HSCs which were undergoing
      early apoptosis. These findings demonstrate for the first time that rat HSCs
      possess functional Erbeta, but not Eralpha, to respond directly to E2 exposure.

PMID- 11527409
TI  - Identification of splicing variants of Frabin with partly different functions and
      tissue distribution.
AB  - Frabin is a GDP/GTP exchange protein for Cdc42 small G protein with actin
      filament-binding activity. Frabin consists of the actin filament-binding domain,
      the Dbl homology domain, the first pleckstrin homology domain, the FYVE-finger
      domain, and the second pleckstrin homology domain in this order from the N
      terminus. Frabin forms filopodia through direct activation of Cdc42 and
      lamellipodia through indirect activation of Rac small G protein. We isolated here
      two smaller splicing variants of frabin and named the original one, middle-size
      one, and smallest one frabin-alpha, -beta, and -gamma, respectively. Frabin-beta
      lacked the second pleckstrin homology domain and frabin-gamma lacked the FYVE
      finger domain and the second pleckstrin homology domain. These three variants
      were expressed in all of the tissues examined but their expression levels are
      different depending on tissues. In L fibroblasts, all the three variants formed
      filopodia. As to lamellipodia, frabin-alpha formed them; frabin-beta formed them
      to a small extent; and frabin-gamma did not. In MDCK epithelial cells, frabin
      alpha formed microspikes but frabin-beta or -gamma did not.

PMID- 11527410
TI  - Archaeoglobus fulgidus RNase HII in DNA replication: enzymological functions and
      activity regulation via metal cofactors.
AB  - RNA primer removal during DNA replication is dependent on ribonucleotide- and
      structure-specific RNase H and FEN-1 nuclease activities. A specific RNase H
      involved in this reaction has long been sought. RNase HII is the only open
      reading frame in Archaeoglobus fulgidus genome, while multiple RNases H exist in
      eukaryotic cells. Data presented here show that RNase HII from A. fulgidus
      (aRNase HII) specifically recognizes RNA-DNA junctions and generates products
      suited for the FEN-1 nuclease, indicating its role in DNA replication.
      Biochemical characterization of aRNase HII activity in the presence of various
      divalent metal ions reveals a broad metal tolerance with a preference for Mg(2+)
      and Mn(2+). Combined mutagenesis, biochemical competitions, and metal-dependent
      activity assays further clarify the functions of the identified amino acid
      residues in substrate binding or catalysis, respectively. These experiments also
      reveal that Asp129 form a second-metal binding site, and thus contribute to
      activity attenuation.

PMID- 11527411
TI  - Developmental expression of alcohol dehydrogenase (ADH3) in zebrafish (Danio
      rerio).
AB  - Alcohol dehydrogenase (ADH) is the primary enzyme responsible for metabolism of
      ethanol to acetaldehyde. One class of ADH has been described in fish, and has
      been found to be structurally similar to mammalian class III ADH (glutathione
      dependent formaldehyde dehydrogenase) but functionally similar to class I ADH
      (primarily responsible for ethanol metabolism). We have cloned a cDNA by RT-PCR
      from zebrafish (Danio rerio) liver representing the zebrafish ADH3 gene product,
      with a coding region of 1131 nucleotides. The deduced amino acid sequences share
      90% identity to ADH3 from the marine fish Sparus aurata, and 82 and 81% identity
      to the mouse and human sequences, respectively. Using a quantitative competitive
      RT-PCR assay, ADH3 mRNA was detected at all timepoints analyzed and was lowest
      between 8 and 24 h postfertilization. Thus, differential ADH3 expression may be
      at least partly responsible for temporal variations in the sensitivity of
      zebrafish embryos to developmental alcohol exposure.

PMID- 11527412
TI  - Interaction of Myc-associated zinc finger protein with DCC, the product of a
      tumor-suppressor gene, during the neural differentiation of P19 EC cells.
AB  - Expression of the DCC (deleted in colorectal cancer) protein is strongly induced
      during the neural differentiation of mouse P19 embryonal carcinoma (EC) cells
      that occurs when these cells are treated with retinoic acid (RA). Myc-associated
      zinc finger protein (MAZ) is a DNA-binding protein that is widely expressed and
      functions in human, mouse and hamster cells as an activator, an initiator or a
      terminator of transcription. However, the biological functions of MAZ remain
      elusive. We report here that MAZ associates with the cytoplasmic domain of the
      DCC protein in vivo and in vitro. Yeast two-hybrid assays confirmed this
      association. An immunofluorescence study demonstrated that DCC protein is
      expressed at elevated levels in neuron-like P19 EC cells, in particular in axons,
      in which the MAZ protein is also expressed. We found that MAZ was translocated
      from the nucleus to the cytoplasm during the RA-induced terminal differentiation
      of P19 EC cells with resultant loss of the ability of MAZ to bind to the ME1a1
      site of the c-myc promoter. Taken together, our observations imply that the DCC
      protein might play a critical role as a signaling molecule in the regulation of
      the transcriptional activity of MAZ during the neural differentiation of P19 EC
      cells.

PMID- 11527413
TI  - Specific tissue distribution of megsin, a novel serpin, in the glomerulus and its
      up-regulation in IgA nephropathy.
AB  - Mesangial cells play critical roles in maintaining a structure and function of
      the glomerulus. We previously cloned a novel mesangium-predominant gene, megsin,
      a new serine protease inhibitor. To clarify localization and roles of megsin
      protein, we raised polyclonal antibodies to megsin. By immunohistochemistry,
      megsin protein was specifically identified in the mesangial area. The amount of
      megsin protein was increased in glomeruli of patients with IgA nephropathy than
      in those of normal individuals and of patients with minimal change nephrotic
      syndrome or membranous nephropathy, suggesting a pathophysiological role of
      megsin as a functional modulator of mesangial functions in situ.

PMID- 11527414
TI  - Cardiac Characteristics of Transgenic Mice Overexpressing Refsum Disease Gene
      Associated Protein within the Heart.
AB  - Arrhythmia is a common cardiac symptom of Refsum disease. Recently, we identified
      a novel neuron-specific PAHX-associated protein (PAHX-AP1), which binds to the
      Refsum disease gene (PAHX). In this report, we developed heart-targeted
      transgenic (TG) mice under the control of alpha-myosin heavy chain promoter to
      determine whether cardiac overexpression of PAHX-AP1 provokes cardiac involvement
      symptoms. Northern and in situ hybridization analyses revealed PAHX-AP1
      transcript was overexpressed in TG atrium, especially in the sinoatrial node. TG
      mice showed tachycardia, and tachyarrhythmia was observed in 20% of TG mice.
      Isolated TG atria showed higher frequency beating and were more sensitive to
      aconitine-induced tachyarrhythmia than the wild-type, and 40% of the TG atria
      showed irregular beating. Action potential duration in TG atrial fiber was
      shortened much more than the wild-type. Systemic administration of arrhythmogenic
      agents induced arrhythmia in TG mice, while no arrhythmia with the same dose in
      nonTG mice. Our results indicate that the chronic atrial tachycardia by
      overexpressed neuron-specific PAHX-AP1 transgene in atrium may be responsible for
      the increased susceptibility to arrhythmia.

PMID- 11527415
TI  - Identification of four Drosophila allatostatins as the cognate ligands for the
      Drosophila orphan receptor DAR-2.
AB  - The allatostatins are generally inhibitory insect neuropeptides. The Drosophila
      orphan receptor DAR-2 is a G-protein-coupled receptor, having 47% amino acid
      residue identity with another Drosophila receptor, DAR-1 (which is also called
      dros. GPCR, or DGR) that was previously shown to be the receptor for an intrinsic
      Drosophila A-type (cockroach-type) allatostatin. Here, we have permanently
      expressed DAR-2 in CHO cells and found that it is the cognate receptor for four
      Drosophila A-type allatostatins, the drostatins-A1 to -A4. Of all the drostatins,
      drostatin-A4 (Thr-Thr-Arg-Pro-Gln-Pro-Phe-Asn-Phe-Gly-Leu-NH(2)) is the most
      effective in causing a second messenger cascade (measured as bioluminescence;
      threshold, 10(-9) M; EC(50), 10(-8) M), whereas the others are less effective and
      about equally potent (EC(50), 8 x 10(-8) M). Northern blots showed that the DAR-2
      gene is expressed in embryos, larvae, pupae, and adult flies. In adult flies, the
      receptor is more strongly expressed in the thorax/abdomen than in the head parts,
      suggesting that DAR-2 is a gut receptor. This is confirmed by Northern blots from
      3rd instar larvae, showing that the DAR-2 gene is mainly expressed in the gut and
      only very weakly in the brain. The Drosophila larval gut also contains about 20
      30 endocrine cells, expressing the gene for the drostatins-A1 to -A4. We suggest,
      therefore, that DAR-2 mediates an allatostatin (drostatin)-induced inhibition of
      gut motility. This is the first report on the permanent and functional expression
      of a Drosophila gut neurohormone receptor.

PMID- 11527416
TI  - Invasiveness of hepatocellular carcinoma cell lines: contribution of hepatocyte
      growth factor, c-met, and transcription factor Ets-1.
AB  - To understand the mechanism of invasion and metastasis of hepatocellular
      carcinoma (HCC), the expression of c-met and Ets-1, and the effect of HGF on
      these cell's motility and invasion ability were examined in four hepatoma cell
      lines. The analysis revealed that the overexpression of c-met and Ets-1 is
      closely connected with the motility and invasion ability of the HCC cell lines.
      Invasion activity of HepG2 and HLE cells were enhanced by the addition of HGF to
      medium. HGF regulated c-met transcription in HepG2 and Bel-7402 cells, HGF also
      induced Ets-1 transcription in Bel-7402 cell. Bel-7402 cells stably transduced
      with the human Ets-1 gene showed significantly increased invasion potentials
      compared to parental and mock-transfected cells. The expression level of c-met,
      MMP1, MMP9, and u-PA in Bel-7402 cells transfected with Ets-1 were markedly
      increased, and as a consequence of c-met expression increase. Bel-7402 cells
      transfected with Ets-1 were more responsive to exogenous HGF stimulation in
      invasiveness and motility ability. In addition, conditioned by antisense Ets-1
      oligonucleotide-treat-Bel-7402 cells transfected with Ets-1 gene and HLE hepatoma
      cells showed markedly reduced invasion activity, and down-regulated the
      transcription of Ets-1, c-met, u-PA, MMP-1, and MMP-9. These results strongly
      suggest that Ets-1 has a crucial role in the invasive property in hepatoma cell
      lines, and there may exist a loop to enhance the invasive ability of hepatoma
      cell lines.

PMID- 11527417
TI  - Processing in the C-terminal domain of minicollagen XII removes a heparin-binding
      site.
AB  - A minicollagen comprising the two C-terminal domains of collagen XII (COL1 and
      NC1) has been expressed in insect cells and characterized biochemically. An
      interaction with heparin is demonstrated, which depends on the correct folding of
      the molecule. After secretion, minicollagen XII is immediately processed to a
      form lacking heparin binding ability. Processed and unprocessed trimers differ
      only at the level of the eight or nine C-terminal residues but they reveal
      different structures as judged from rotary shadowing images. Similar processing
      is also observed in the medium of transfected human HeLa cells. These data show
      that a heparin-binding site is present in the C-terminal end of the chicken
      collagen XII sequence and strongly suggest that proteolytic processing in the NC1
      domain can occur in vivo and regulate the interactive properties of collagen XII.

PMID- 11527418
TI  - Activation of p44/p42 mitogen-activated protein kinase limits triiodothyronine
      stimulated alkaline phosphatase activity in osteoblasts.
AB  - It has been shown that thyroid hormone stimulates the activity of alkaline
      phosphatase, a marker of mature osteoblast phenotype, in osteoblasts. In the
      present study, we investigated whether p44/p42 mitogen-activated protein (MAP)
      kinase is involved in the thyroid hormone-stimulated alkaline phosphatase
      activity in osteoblast-like MC3T3-E1 cells. Triiodothyronine (T(3)) markedly
      induced the phosphorylation of p44/p42 MAP kinase. PD98059 and U0126, inhibitors
      of the upstream kinase that activates p44/p42 MAP kinase, significantly enhanced
      the T(3)-induced alkaline phosphatase activity in a dose-dependent manner. The
      phosphorylation of p44/p42 MAP kinase induced by T(3) was reduced by U0126. These
      results strongly suggest that p44/p42 MAP kinase takes part in the thyroid
      hormone-stimulated alkaline phosphatase activity in osteoblasts and that p44/p42
      MAP kinase plays an inhibitory role in the thyroid hormone-effect.

PMID- 11527419
TI  - R(+)-methanandamide induces cyclooxygenase-2 expression in human neuroglioma
      cells via a non-cannabinoid receptor-mediated mechanism.
AB  - Cannabinoids affect prostaglandin (PG) formation in the central nervous system
      through as yet unidentified mechanisms. Using H4 human neuroglioma cells, the
      present study investigates the effect of R(+)-methanandamide (metabolically
      stable analogue of the endocannabinoid anandamide) on the expression of the
      cyclooxygenase-2 (COX-2) enzyme. Incubation of cells with R(+)-methanandamide was
      accompanied by concentration-dependent increases in COX-2 mRNA, COX-2 protein,
      and COX-2-dependent PGE(2) synthesis. Moreover, treatment of cells with R(+)
      methanandamide in the presence of interleukin-1beta led to an overadditive
      induction of COX-2 expression. The stimulatory effect of R(+)-methanandamide on
      COX-2 expression was mimicked by the structurally unrelated cannabinoid Delta(9)
      tetrahydrocannabinol. Stimulation of both COX-2 mRNA expression and subsequent
      PGE(2) synthesis by R(+)-methanandamide was not affected by the selective CB(1)
      receptor antagonist AM-251 or the G(i/o) protein inactivator pertussis toxin.
      Enhancement of COX-2 expression by R(+)-methanandamide was paralleled by time
      dependent phosphorylations of p38 mitogen-activated protein kinase (MAPK) and
      p42/44 MAPK. Consistent with the activation of both kinases, R(+)-methanandamide
      induced COX-2 mRNA expression and PGE(2) formation were abrogated in the presence
      of specific inhibitors of p38 MAPK (SB203580) and p42/44 MAPK activation
      (PD98059). Together, our results demonstrate that R(+)-methanandamide induces COX
      2 expression in human neuroglioma cells via a cannabinoid receptor-independent
      mechanism involving activation of the MAPK pathway. In conclusion, induction of
      COX-2 expression may represent a novel mechanism by which cannabinoids mediate PG
      dependent effects within the central nervous system.

PMID- 11527420
TI  - Estrogen effects in the myocardium: inhibition of NF-kappaB DNA binding by
      estrogen receptor-alpha and -beta.
AB  - We have previously shown that estrogen effects in the heart include direct
      hormone effects on the myocardium. In a recent study we found that one beneficial
      effect of estradiol on the myocardium is the inhibition of apoptosis in cardiac
      myocytes. This effect was associated with a reduction of NF-kappaB activity. In
      the present study we have analyzed the functional mechanism of NF-kappaB
      inhibition in the myocardium by estrogen receptors-alpha and -beta. Despite the
      previous finding that 17-beta-estradiol (10 nM) inhibited the staurosporine
      induced binding of p65/p50 NF-kappaB complexes to their cognate DNA elements in
      cultured rat cardiac myocytes, myocyte extracts showed no change in expression or
      cellular localization of p65, p50, and IkappaB upon staurosporine or estradiol
      treatment. Addition of either estrogen receptor-alpha or estrogen receptor-beta
      as recombinant protein was sufficient to inhibit staurosporine-dependent p65/p50
      DNA binding in cardiac myocytes. 17-beta-Estradiol inhibits staurosporine-induced
      p65/p50 DNA binding associated with apoptotic cell death of cardiac myocytes via
      estrogen receptors-alpha and -beta. This is not associated with changes in p65,
      p50 and IkappaB expression or subcellular localization. Thus, inhibition of NF
      kappaB activity by estrogenic compounds might inhibit NF-kappaB dependent gene
      expression such as pro-inflammatory cytokines in the myocardium.

PMID- 11527421
TI  - Phosphoenolpyruvate carboxylase kinase is controlled by a similar signaling
      cascade in CAM and C(4) plants.
AB  - In Crassulacean acid metabolism (CAM) plants, phosphoenolpyruvate carboxylase
      (PEPC) is subject to day-night regulatory phosphorylation of a conserved serine
      residue in the plant enzyme's N-terminal domain. The dark increase in PEPC-kinase
      (PEPC-k) activity is under control of a circadian oscillator, via the enhanced
      expression of the corresponding gene (1). The signaling cascade leading to PEPC-k
      up-regulation was investigated in leaves and mesophyll cell protoplasts of the
      facultative, salt-inducible CAM species, Mesembryanthemum crystallinum. Mesophyll
      cell protoplasts had the same PEPC-k activity as leaves from which they were
      prepared (i.e., high at night, low during the day). However, unlike C(4)
      protoplasts (2), CAM protoplasts did not show marked PEPC-k up-regulation when
      isolated during the day and treated with a weak base such as NH(4)Cl.
      Investigations using various pharmacological reagents established the operation,
      in the darkened CAM leaf, of a PEPC-k cascade including the following components:
      a phosphoinositide-dependent phospholipase C (PI-PLC), inositol 1,4,5 P (IP(3))
      gated tonoplast calcium channels, and a putative Ca(2+)/calmodulin protein
      kinase. These results suggest that a similar signaling machinery is involved in
      both C(4) (2, 3) and CAM plants to regulate PEPC-k activity, the phosphorylation
      state of PEPC, and, thus, carbon flux through this enzyme during CAM
      photosynthesis.

PMID- 11527422
TI  - Characterization of the DNA-binding property of Smad5.
AB  - Activation of TGF-beta superfamily receptors leads to phosphorylation of Smad
      proteins which function as transcription factors to regulate gene expression.
      Previous studies have indicated that Smad5, together with Smad1 and Smad8,
      participates in signaling downstream of BMP receptors. To characterize the DNA
      binding characteristics of Smad5, we used the GST-Smad5 N-terminal fusion protein
      to select for random oligonucleotide sequences that were able to binds the
      protein. As a result, we found that Smad5 is able to bind a consensus sequence
      TGTGC. We further used the Smad7 promoter sequence that contains a Smad-binding
      element (SBE), GTCTAGAC to determine how mutations in each nucleotide in the SBE
      affects the binding with Smad5, compared with the binding with Smad1, Smad2,
      Smad3, Smad4, and Smad8. Interestingly, Smad5, but not Smad1 and Smad8, was able
      to bind the SBE, at a level similar to the binding by Smad3 and Smad4. However,
      mutations at the SBE had different effect on the binding with Smad5, compared to
      that with Smad3 and Smad4. These studies suggest that even though Smad5 falls
      into the same subfamily with Smad1 and Smad8 in mediating the signaling by BMP
      receptors, it has an unique DNA-binding property that is similar to Smad3, which
      specifically transduces signaling for TGF-beta and activin receptors.

PMID- 11527423
TI  - Isolation and preliminary biological assessment of AADGAPLIRFamide and
      SVPGVLRFamide from Caenorhabditis elegans.
AB  - To date, 9 FMRFamide-related peptides (FaRPs) have been structurally
      characterised from Caenorhabditis elegans. Radioimmunometrical screening of an
      ethanolic extract of C. elegans revealed the presence of two additional FaRPs
      that were purified by reverse-phase HPLC and subjected to Edman degradation
      analysis and gas-phase sequencing. Unequivocal primary structures for the two
      FaRPs were determined as Ala-Ala-Asp-Gly-Ala-Pro-Leu-Ile-Arg-Phe-NH(2) and Ser
      Val-Pro-Gly-Val-Leu-Arg-Phe-NH(2). Using MALDI-TOF mass spectrometry, the
      molecular masses of the peptides were found to be 1032 Da (MH) and 875 Da
      (MH)(+), respectively. Two copies of AADGAPLIRFamide are predicted to be encoded
      on the precursor gene termed flp-13, while one copy of SVPGVLRFamide is located
      on flp-18. Synthetic replicates of the peptides were tested on Ascaris suum
      somatic muscle to assess bioactivity. ADDGAPLIRFamide had inhibitory effects on
      A. suum muscle strips, which occurred over a range of concentrations from a
      threshold for activity of 10 nM to 10 microM. SVPGVLRFamide was excitatory on A.
      suum somatic musculature from a threshold concentration for activity of 1 nM to
      10 microM. The inhibitory and excitatory effects of AADGAPLIRFamide and
      SVPGVLRFamide, respectively, were the same for dorsal and ventral muscle strips
      as well as innervated and denervated preparations, suggesting that these
      physiological effects are not nerve cord dependent. Addition of ADDGAPLIRFamide
      (10 microM) to muscle strips preincubated in high-K(+) and -Ca(2+)-free medium
      resulted in a normal inhibitory response. Peptide addition to muscle strips
      preincubated in Cl(-)-free medium showed no inhibitory response, suggesting that
      the inhibitory response of the peptide may be chloride mediated. A normal
      excitatory response was noted following the addition of 10 microM SVPGVLRFamide
      to muscle strips preincubated in high-K(+), Ca(2+)- and Cl(-)-free media.

PMID- 11527424
TI  - Decreased DMPK transcript levels in myotonic dystrophy 1 type IIA muscle fibers.
AB  - Myotonic dystrophy 1 is caused by the expansion of a CTG trinucleotide repeat on
      chromosome 19q13.3. The repeat lies in the 3' untranslated region of the myotonic
      dystrophy protein kinase gene (DMPK), and it has been hypothesised that the
      expansion alters the expression levels of DMPK and/or its neighbouring genes,
      DMWD and SIX5. Published data remain controversial, partly due to the mixed cell
      populations found in most tissues examined. We have microdissected human skeletal
      muscle biopsies from myotonic dystrophy 1 patients and controls and analysed gene
      expression at this locus for type I and type IIA fibres, using quantitative real
      time reverse transcription-polymerase chain reaction. Levels of DMPK expression
      were specifically decreased in the type IIA fibres of myotonic dystrophy
      patients, below the levels found in controls. This suggests that DMPK expression
      is altered in this disease, suggesting significant pathological consequences.

PMID- 11527425
TI  - Ceramide blocks PDGF-induced DNA synthesis in mesangial cells via inhibition of
      Akt kinase in the absence of apoptosis.
AB  - The mechanism of action of ceramide in glomerular mesangial cells has not been
      studied. We investigated the effect of C2 ceramide on the mitogenic signal
      transduction pathways induced by PDGF in mesangial cells. Increasing
      concentrations of C2 ceramide inhibited PDGF-induced DNA synthesis in a dose
      dependent manner with maximum inhibition at 15 microM. This inhibition of DNA
      synthesis was associated with attenuation of PDGF-induced early response gene c
      fos transcription. PDGF receptor beta immunecomplex kinase assay showed no
      inhibitory effect of C2 ceramide on PDGF receptor tyrosine kinase activity. We
      have recently shown that the mitogenic effect of PDGF is mediated by the enzyme
      phosphatidylinositol (PI) 3 kinase in mesangial cells. C2 ceramide had no effect
      on PDGF-induced PDGFR-associated PI 3 kinase activity. These data indicate that
      inhibitory effect of C2 on PDGF-induced DNA synthesis is likely due to post
      receptor and post-PI 3 kinase events. To address the mechanism of C2-mediated
      inhibition of DNA synthesis, we investigated the downstream target of PI 3
      kinase, Akt. PDGF time-dependently increased Akt kinase activity in a PI 3 kinase
      dependent manner. Incubation of mesangial cells with C2 ceramide inhibited PDGF
      induced Akt activity. Akt kinase inhibits apoptosis of cells via phosphorylation
      of multiple proapoptotic proteins. However, inhibition of Akt activity by C2
      ceramide did not induce apoptosis in mesangial cells. These data provide the
      first evidence that in mesangial cells, ceramide cross-talks with PI 3 kinase
      dependent Akt kinase to inhibit PDGF-induced DNA synthesis without inducing
      apoptosis.

PMID- 11527426
TI  - Manifold reduction of moesin in fetal Down syndrome brain.
AB  - Moesin is a member of the ERM family and is involved in plasma membrane-actin
      cytoskeleton cross-linking, resulting cell adhesion, shape, and motility. Because
      moesin was shown to be highly expressed in growth cones and moesin/radixin
      suppression led to impaired structure and function of this key element in brain
      development, we tested the ERM family, ezrin, radixin, and moesin, in fetal Down
      syndrome (DS) cortex at the early second trimester. We applied two-dimensional
      gel electrophoresis with subsequent MALDI detection and identification of protein
      spots followed by quantification with specific software. Moesin was shown to be
      significantly and manifold reduced in fetal DS brain, whereas reduction of ezrin
      and radixin did not reach statistical significance. We therefore propose the
      involvement of moesin in developmental impairment of DS brain, including
      deteriorated arborisation, neuritic outgrowth, and neuronal migration.
      Furthermore, decreased moesin is the second F-actin bundling protein, besides
      drebrin, that is manifold reduced in fetal DS brain.

PMID- 11527428
TI  - 3D model for TM region of the AT-1 receptor in complex with angiotensin II
      independently validated by site-directed mutagenesis data.
AB  - A three-dimensional model of the complex of angiotensin II (AII) with the
      transmembrane (TM) region of the angiotensin II receptor of type 1 (the AT-1
      receptor) was obtained by molecular modeling procedures employing structural
      homology to the X-ray structure of rhodopsin. Since the modeling procedure
      considered only steric and energy considerations without prior knowledge of the
      experimental results of site-directed mutagenesis, the results with receptor
      mutants could be used for independent validation of the model. Indeed, the model
      brings in contact the residues of AII responsible for agonistic activity, Tyr(4),
      His(6), and Phe(8), with many residues of AT-1 involved in signal transduction
      according to site-directed mutagenesis. The model also predicts the existence of
      several possible conformational pathways for transferring the binding signal
      through the TM region of AT-1 to the intracellular loops interacting with the G
      protein.

PMID- 11527427
TI  - Design and evaluation of a tryptophanless RecA protein with wild type activity.
AB  - The C-terminal domain of the Escherichia coli RecA protein contains two
      tryptophan residues whose native fluorescence emission provides an interfering
      background signal when other fluorophores such as 1,N(6)-ethenoadenine, 2
      aminopurine and other tryptophan residues are used to probe the protein's
      activities. Replacement of the wild type tryptophans with nonfluorescent residues
      is not trivial because one tryptophan is highly conserved and the C-terminal
      domain functions in both DNA binding as well as interfilament protein-protein
      contact. We undertook the task of creating a tryptophanless RecA protein with WT
      RecA activity by selecting suitable amino acid replacements for Trp290 and
      Trp308. Mutant proteins were screened in vivo using assays of SOS induction and
      cell survival following UV irradiation. Based on its activity in these assays,
      the W290H-W308F W-less RecA was purified for in vitro characterization and
      functioned like WT RecA in DNA-dependent ATPase and DNA strand exchange assays.
      Spectrofluorometry indicates that the W290H-W308F RecA protein generates no
      significant emission when excited with 295-nm light. Based on its ability to
      function as wild type protein in vivo and in vitro, this dark RecA protein will
      be useful for future fluorescence experiments.

PMID- 11527429
TI  - Binding to intracellular targets of the metastasis-inducing protein, S100A4
      (p9Ka).
AB  - Experimentally elevated levels of S100A4 induce a metastatic phenotype in benign
      mammary tumour cells in vivo. In humans, the presence of S100A4 in breast cancer
      cells correlates strongly with reduced patient survival. Potential interacting
      binding partners for S100A4 have now been examined using an optical biosensor.
      There was significant interaction of S100A4 with non-muscle myosin and p53, but
      not with actin, tropomyosin or tubulin. The results suggest that myosin and p53
      are likely to be intracellular targets of S100A4. S100A4 had a greater affinity
      for wild-type or mutant arg-175-his p53 than for non-muscle myosin. The results
      suggest that S100A4 might induce metastasis by influencing the function of p53 as
      well as through its interaction with myosin and that any mechanism is independent
      of the mutational status of p53.

PMID- 11527430
TI  - 8-N(3)-3'-biotinyl-ATP, a novel monofunctional reagent: differences in the F(1)-
      and V(1)-ATPases by means of the ATP analogue.
AB  - A novel photoaffinity label, 8-N(3)-3'-biotinyl-ATP, has been synthesized. The
      introduction of an additional biotin residue is advantageous for easy detection
      of labeled proteins. This could be first tested by reaction with the F(1)-ATPase
      from the thermophilic bacterium PS3 (TF(1)). UV irradiation of TF(1) in the
      presence of 8-N(3)-3'-biotinyl-ATP results in a nucleotide-dependent binding of
      the analogue in the noncatalytic alpha and the catalytic beta subunits of TF(1),
      demonstrating the suitability of this analogue as a potential photoaffinity
      label. Reaction with the V(1)-ATPase, however, led to labeling of subunit E,
      which has been suggested as a structural and functional homologue of the gamma
      subunit of the F-ATPases. MALDI-TOF mass spectrometry has been used to map the
      regions of subunit E involved in the binding of 8-N(3)-3'-biotinyl-ATP.

PMID- 11527431
TI  - Characterization of interactions between Nedd4 and beta and gammaENaC using
      surface plasmon resonance.
AB  - Cell surface expression of the epithelial Na(+) channel ENaC is regulated by the
      ubiquitin ligase Nedd4. Binding of the WW domains of Nedd4 to the PY region in
      the carboxy tails of beta and gammaENaC, results in channel ubiquitination and
      degradation. Kinetic analysis of these interactions has been done using surface
      plasmon resonance. Synthetic peptides corresponding to the PY regions of beta and
      gammaENaC were immobilized on a sensor chip and "real-time" kinetics of their
      binding to recombinant WW proteins was determined. Specificity of the
      interactions was established by competition experiment, as well as by monitoring
      effects of a point mutation known to impair Nedd4/ENaC binding. These data
      provides the first determination of association, dissociation and equilibrium
      constants for the interactions between WW2 and beta or gammaENaC.

PMID- 11527432
TI  - Some attractions of verb agreement.
AB  - In English, words like scissors are grammatically plural but conceptually
      singular, while words like suds are both grammatically and conceptually plural.
      Words like army can be construed plurally, despite being grammatically singular.
      To explore whether and how congruence between grammatical and conceptual number
      affected the production of subject-verb number agreement in English, we elicited
      sentence completions for complex subject noun phrases like The advertisement for
      the scissors. In these phrases, singular subject nouns were followed by
      distractor words whose grammatical and conceptual numbers varied. The incidence
      of plural attraction (the use of plural verbs after plural distractors) increased
      only when distractors were grammatically plural, and revealed no influence from
      the distractors' number meanings. Companion experiments in Dutch offered
      converging support for this account and suggested that similar agreement
      processes operate in that language. The findings argue for a component of
      agreement that is sensitive primarily to the grammatical reflections of number.
      Together with other results, the evidence indicates that the implementation of
      agreement in languages like English and Dutch involves separable processes of
      number marking and number morphing, in which number meaning plays different
      parts.

PMID- 11527433
TI  - Representing properties locally.
AB  - Theories of knowledge such as feature lists, semantic networks, and localist
      neural nets typically use a single global symbol to represent a property that
      occurs in multiple concepts. Thus, a global symbol represents mane across HORSE,
      PONY, and LION. Alternatively, perceptual theories of knowledge, as well as
      distributed representational systems, assume that properties take different local
      forms in different concepts. Thus, different local forms of mane exist for HORSE,
      PONY, and LION, each capturing the specific form that mane takes in its
      respective concept. Three experiments used the property verification task to
      assess whether properties are represented globally or locally (e.g., Does a PONY
      have mane?). If a single global form represents a property, then verifying it in
      any concept should increase its accessibility and speed its verification later in
      any other concept. Verifying mane for PONY should benefit as much from having
      verified mane for LION earlier as from verifying mane for HORSE. If properties
      are represented locally, however, verifying a property should only benefit from
      verifying a similar form earlier. Verifying mane for PONY should only benefit
      from verifying mane for HORSE, not from verifying mane for LION. Findings from
      three experiments strongly supported local property representation and ruled out
      the interpretation that object similarity was responsible (e.g., the greater
      overall similarity between HORSE and PONY than between LION and PONY). The
      findings further suggest that property representation and verification are
      complicated phenomena, grounded in sensory-motor simulations.

PMID- 11527434
TI  - Plasmodium gallinaceum: ookinete formation and proteolytic enzyme dynamics in
      highly refractory Aedes aegypti populations.
AB  - Despite significant progress in the identification of the genetic basis of the
      refractory phenotype, little is known about the physiological mechanism of
      refractoriness. This study therefore examined the physiological basis of mosquito
      refractoriness in the Aedes aegypti/P. gallinaceum system, in which a selected
      refractory strain does not permit Plasmodium oocyst formation. We examined the
      kinetics of two major proteolytic enzymes involved in blood meal digestion and
      the dynamics of ookinete formation for two refractory populations (strains Moyo-R
      and Formosus) and one susceptible population (strain Red). Healthy ookinetes were
      observed in both the susceptible and the refractory populations, although the
      susceptible population generally exhibited higher enzymatic activity for trypsin
      and aminopeptidase than the refractory populations. Parasite numbers in the
      susceptible Red population showed a 4- to 7-fold decrease in abundance during the
      transition from the ookinete stage to the oocyst stage, far less than the
      refractory populations (30- to 92-fold reduction). Due to its smaller body size,
      Moyo-R individuals generally ingest a smaller blood meal and thus intake fewer
      gametocytes than Red individuals. Thus, the possibility that refractoriness in
      the Moyo-R population results from fewer gametocytes being ingested is examined.
      We found that the Red population remained highly susceptible and the Moyo-R
      population stayed refractory when those individuals with similar blood meal size
      were compared. We conclude that failure of oocyst development in the refractory
      mosquitoes is not due to ookinete damage by proteolytic enzymes or to fewer
      gametocytes being ingested, but rather is due to a midgut barrier or to some
      other mechanism.

PMID- 11527435
TI  - Exogenous interleukin-12 (IL-12) exacerbates Cryptosporidium parvum infection in
      gamma interferon knockout mice.
AB  - Experimental infection of BALB/c- or C57BL/6-gamma-interferon-knockout (GKO) mice
      with Cryptosporidium parvum results in infection in both strains with different
      outcomes of disease. The BALB/c-GKO mice recover from infection, whereas the
      C57BL/6-GKO mice succumb to infection in less than 2 weeks. Differences in
      cytokine mRNA expression suggested that recovery may involve other cytokines. To
      determine whether the addition of either a Th1 or Th2 cytokine could alter the
      outcome of infection, we treated GKO mice with either recombinant (r)IL-4 or rIL
      12 1 day before infection (DBI) or daily. No effect on the oocyst shedding
      patterns in either strain nor an increase in survival of the C57BL/6-GKO mice was
      observed in the rIL-4-treated mice. Whereas one dose of 0.5 microg rIL-12 given 1
      DBI had no effect on oocyst shedding, we found that daily doses of rIL-12
      administered intraperitoneally exacerbated C. parvum infection in both animal
      models. Administration of rIL-12 shortened the survival time in the C57BL/6-GKO
      mice and prevented BALB/c-GKO mice from recovering from infection. Specific
      proliferation of T cells to cryptosporidial antigen and Th1 and Th2 mRNA cytokine
      expression was markedly decreased in rIL-12-treated mice. Nitric oxide (NO) may
      have played a minor role in the decreased proliferation observed since levels of
      NO present in the splenocyte cultures from rIL-12-treated mice in response to
      parasite antigen stimulation were higher than those observed in controls. Thus,
      we propose that resistance to and recovery from C. parvum infections involves a
      fine balance in the amount and timing of Th1 and Th2 cytokines.

PMID- 11527436
TI  - Receptor-mediated endocytosis in an apicomplexan parasite (Toxoplasma gondii).
AB  - Endocytosis mechanisms are poorly known in apicomplexan parasites. Here, we show
      that extracellular tachyzoites of Toxoplasma gondii bind and internalize heparin
      like sulfated glycans in a specific, saturable manner. Discrete binding of the
      glycan occurs at the anterior third of the tachyzoite, where it is rapidly
      concentrated inside single tubulo vesicular compartments that become multiple
      with time. The compound is held for several hours intracellularly with no
      apparent exocytosis or acidification. Incubation in the continuous presence of
      fluorescein isothiocyanate-conjugated heparin enhances the binding and
      internalization of this ligand by live tachyzoites. Two tachyzoite surface
      polypeptides exhibit strong binding and specificity for heparin, making them
      candidate receptors. Uptake of fluid-phase endocytic tracers occurs via
      nonspecific pinocytosis in the same region of the parasite cell, but with much
      lower efficiency. These observations show that extracellular tachyzoites can
      acquire molecules through both receptor-specific and fluid-phase endocytic
      mechanisms. Understanding the physiological relevance of these processes for the
      extracellular and intracellular stages of T. gondii may bring about direct
      targeting of the parasite by drug delivery into the tachyzoites.

PMID- 11527437
TI  - Entamoeba invadens: enhancement of excystation and metacystic development by
      cytochalasin D.
AB  - Effects of three actin-modifying drugs, cytochalasin D, latrunculin A, and
      jasplakinolide, on the excystation and metacystic development in vitro of
      Entamoeba invadens were examined by transfer of the cysts to growth medium with
      the drugs. Cytochalasin D unexpectedly increased the number of metacystic amoebae
      of E. invadens strain IP-1 during incubation. Metacystic development, which was
      determined by the number of nuclei of metacystic amoebae, was faster in the
      culture with cytochalasin D than in the culture without the drug. These results
      suggest that cytochalasin D enhances the excystation and metacystic development.
      In contrast, latrunculin A and jasplakinolide inhibited these process. No
      excystation occurred in encystation medium even in the presence of cytochalasin
      D, suggesting that growth medium is essential for excystation. Excystation was
      further enhanced when the cysts were incubated with cytochalasin D before culture
      in growth medium with the drug. The enhancing effect of cytochalasin D on the
      excystation and metacystic development was abrogated by jasplakinolide. Thus, the
      results indicate that cytochalasin D, unlike latrunculin A and jasplakinolide,
      caused enhancement of the excystation and metacystic development of this
      parasite.

PMID- 11527438
TI  - Plasmodium vivax: ookinete destruction and oocyst development arrest are
      responsible for Anopheles albimanus resistance to circumsporozoite phenotype
      VK247 parasites.
AB  - Anopheles albimanus and An. pseudopunctipennis differ in their susceptibilities
      to Plasmodium vivax circumsporozoite phenotypes. An. pseudopunctipennis is
      susceptible to phenotype VK247 but almost refractory to VK210. In contrast, An.
      albimanus is almost refractory to VK247 but susceptible to VK210. To investigate
      the site in the mosquito and the parasite stage at which resistance mechanisms
      affect VK247 development in An. albimanus, parasite development was followed in a
      series of experiments in which both mosquitoes species were simultaneously
      infected with blood from patients. Parasite phenotype was determined in mature
      oocysts and salivary gland sporozoites by use of immunofluorescence and Western
      blot assays and/or gene identification. Ookinete maturation and their densities
      within the bloodmeal bolus were similar in both mosquito species. Ookinete
      densities on the internal midgut surface of An. albimanus were 4.7 times higher
      than those in An. pseudopunctipennis; however, the densities of developing
      oocysts on the external midgut surface were 6.12 times higher in the latter
      species. Electron microscopy observation of ookinetes in An. albimanus midgut
      epithelium indicated severe parasite damage. These results indicate that P. vivax
      VK247 parasites are destroyed at different parasite stages during migration in
      An. albimanus midguts. A portion, accumulated on the internal midgut surface, is
      probably destroyed by the mosquito's digestive enzymes and another portion is
      most likely destroyed by mosquito defense molecules within the midgut epithelium.
      A third group, reaching the external midgut surface, initiates oocyst
      development, but over 90% of them interrupt their development and die. The
      identification of mechanisms that participate in parasite destruction could
      provide new elements to construct transgenic mosquitoes resistant to malaria
      parasites.

PMID- 11527439
TI  - Lack of DNA methylation in Schistosoma mansoni.
AB  - Schistosoma mansoni genomic DNA from male and female adult worms was subjected to
      restriction by the isoschizomeric endonucleases HpaII and MspI, which display
      different sensitivities with respect to cytosine methylation. The digested DNA
      was hybridized with 13 S. mansoni probes. Southern blot analysis showed that
      there were no observable differences in the restriction patterns of the two
      isoschizomers and that the patterns were identical in male and female parasites.
      Adenine methylation was also ruled out since no differences were observed with
      DpnI, Sau3A1, or MboI restriction enzymes. The methylation-dependent restriction
      endonuclease McrBC, which cleaves DNA containing methylcytosine and will not
      cleave unmethylated DNA, did not digest S. mansoni genomic DNA. These results
      demonstrate that the genome of adult S. mansoni is not methylated.

PMID- 11527440
TI  - Toxoplasma gondii: genetic selection of tethered dihydrofolate reductase
      thymidylate synthase fusion proteins.

PMID- 11527441
TI  - On the principles of the vascular network branching.
AB  - We propose an explanation of Murray's law without applying the minimality
      principles. The model deals with a "delivering" artery system of an organ that is
      characterized, first, by the space-filling embedding into the organ tissue and,
      second, by the uniform distribution of the blood pressure drop over it. The
      latter assumption is justified using the available physiological data and the
      idea about conditions needed for perfect self-regulation. Based on the two
      statements we get Murray's law, and so, demonstrate that it can be also regarded
      as a direct consequence of the organism's capacity for controlling finely the
      blood flow redistribution over peripheral vascular networks.

PMID- 11527442
TI  - Diversity patterns from ecological models at dynamical equilibrium.
AB  - We study a dynamic model of ecosystems where an immigration flux assembles the
      species community and maintains its biodiversity. This framework is particularly
      relevant for insular ecosystems. Population dynamics is represented either as an
      individual-based model or as a set of deterministic equations for population
      abundances. Local extinctions and immigrations balance at a statistically
      stationary state where biodiversity fluctuates around a constant mean value. We
      find a number of scaling laws characterizing this stationary state. In
      particular, the number of species increases as a power law of the immigration
      rate. With additional assumptions on the immigration flux, we obtain species-area
      relationships in agreement with observations for archipelagos. We also find power
      law distributions for species abundances and lifetimes.

PMID- 11527443
TI  - Exploring protein sequence space using knowledge-based potentials.
AB  - Knowledge-based potentials can be used to decide whether an amino acid sequence
      is likely to fold into a prescribed native protein structure. We use this idea to
      survey the sequence-structure relations in protein space. In particular, we test
      the following two propositions which were found to be important for efficient
      evolution: the sequences folding into a particular native fold form extensive
      neutral networks that percolate through sequence space. The neutral networks of
      any two native folds approach each other to within a few point mutations.
      Computer simulations using two very different potential functions, M. Sippl's
      PROSA pair potential and a neural network based potential, are used to verify
      these claims.

PMID- 11527444
TI  - Link between truncated fractals and coupled oscillators in biological systems.
AB  - This article aims at providing a new theoretical insight into the fundamental
      question of the origin of truncated fractals in biological systems. It is well
      known that fractal geometry is one of the characteristics of living organisms.
      However, contrary to mathematical fractals which are self-similar at all scales,
      the biological fractals are truncated, i.e. their self-similarity extends at most
      over a few orders of magnitude of separation. We show that nonlinear coupled
      oscillators, modeling one of the basic features of biological systems, may
      generate truncated fractals: a truncated fractal pattern for basin boundaries
      appears in a simple mathematical model of two coupled nonlinear oscillators with
      weak dissipation. This fractal pattern can be considered as a particular hidden
      fractal property. At the level of sufficiently fine precision technique the
      truncated fractality acts as a simple structure, leading to predictability, but
      at a lower level of precision it is effectively fractal, limiting the
      predictability of the long-term behavior of biological systems. We point out to
      the generic nature of our result.

PMID- 11527445
TI  - The geometry of shape space: application to influenza.
AB  - Shape space was proposed over 20 years ago as a conceptual formalism in which to
      represent antibody/antigen binding. It has since played a key role in
      computational immunology. Antigens and antibodies are considered to be points in
      an abstract "shape space", where coordinates of points in this space represent
      generalized physico-chemical properties associated with various (unspecified)
      physical properties related to binding, such as geometric shape, hydrophobicity,
      charge, etc. Distances in shape space between points representing antibodies and
      (the shape complement) of antigens are assumed to be related to their affinity,
      with small distances corresponding to high affinity. In this paper, we provide
      algorithms, related to metric and ordinal multidimensional scaling algorithms
      first developed in the mathematical psychology literature, which construct
      explicit, quantitative coordinates for points in shape space given experimental
      data such as hemagglutination inhibition assays, or other general affinity
      assays. Previously, such coordinates had been conceptual constructs and totally
      implicit. The dimension of shape space deduced from hemagglutination inhibition
      assays for influenza is low, approximately five dimensional. The deduction of the
      explicit geometry of shape space given experimental affinity data provides new
      ways to quantify the similarity of antibodies to antibodies, antigens to
      antigens, and the affinity of antigens to antibodies. This has potential utility
      in, e.g. strain selection decisions for annual influenza vaccines, among other
      applications. The analysis techniques presented here are not restricted to the
      analysis of antibody-antigen interactions and are generally applicable to
      affinity data resulting from binding assays.

PMID- 11527446
TI  - Describing the pumping heart as a pressure source.
AB  - The pumping heart is described by a new mathematical approach which considers the
      heart as a pressure source depending on time, volume and flow. This new approach
      allows a separation between isovolumic (non-ejecting) and ejecting heart
      properties. The computed results cover most of the features of the human
      ventricle during normal and altered vascular conditions. It is shown that the
      time-varying elastance concept is disqualified as an independent description of
      the heart, it follows from isovolumic heart properties and an ejection effect
      which consists of positive and negative effects of ventricular blood ejection.

PMID- 11527447
TI  - Engineered underdominance allows efficient and economical introgression of traits
      into pest populations.
AB  - A novel form of underdominance is suggested as a mechanism that is able to drive
      desired genes into pest populations through the release of transgenic individuals
      over one or more generations. Such a mechanism is urgently needed by those
      working to reduce the impact of malaria by releasing strains of Anopheles, the
      vector of the disease, that are not susceptible to malaria parasites. We use
      simple population genetics models to quantify the benefits conferred when
      heterozygous genotypes, arising from matings between introduced and wild
      individuals, are not viable. In a randomly mating population, underdominant
      systems accelerate introgression of desired alleles and allow the release of
      individuals to be discontinued once the frequency of transgenic alleles attains a
      threshold. A set of two constructs, which together are selectively neutral but
      lethal when one is carried without the other, are found to produce dynamics that
      are characteristic of underdominant systems. When these constructs are carried on
      non-homologous chromosomes, then the ratio of released to natural born
      individuals need only be greater than 3:100 for introgression to occur.
      Furthermore, the threshold for the gene frequencies over which the introduced
      genes are expected to become fixed upon discontinuing the release of transgenic
      individuals is surprisingly low. The location of the threshold suggests that the
      introduced genes are expected to spread in space, at least locally. For the first
      time, the prospect of a practical drive mechanism for the genetic manipulation of
      pest populations is raised.

PMID- 11527448
TI  - Survival of replicators with parabolic growth tendency and exponential decay.
AB  - The claim that the competition of parabolically growing self-replicators leads to
      dynamically stable coexistence was challenged by Lifson & Lifson [(1999). J.
      theor. Biol.199, 425-433]. They have shown that, if single- and double-strands
      are treated separately, and only single-strands undergo spontaneous decay, then
      there is natural selection rather than survival of everybody. We use their models
      to show that if double-strand decay is not neglected, then dynamical coexistence
      is still possible under a wide range of parameter values, in agreement with the
      chromatographized replicator model of von Kiedrowski & Szathmary [(2000).
      Selection 1-3, 173-179]. Coexistence is always ensured above a critical resource
      (monomer) inflow rate. Recycling of decayed replicators into monomers further
      favours dynamical coexistence. The claim that parabolic growth invariably results
      in coexistence remains valid for the model for which it was meant to apply,
      namely for parabolic growth without template decay. Exponential decay acting on
      single- and double-strands, combined with parabolic growth, may or may not result
      in a dynamical coexistence of self-replicators.

PMID- 11527449
TI  - Coexistence and Darwinian selection among replicators: response to the preceding
      paper by Scheuring and Szathmary.

PMID- 11527450
TI  - Stochastic effects in intercellular calcium spiking in hepatocytes.
AB  - We carry out a Monte Carlo simulation of stochastic effects for two models of
      intercellular calcium wave propagation in rat hepatocytes. Both models involve
      gap junction diffusion by a second messenger. We find that, in general, the
      stochastic effects improve agreement with experiment, for a reasonable choice of
      model parameters. Both stochastic models exhibit baseline fluctuations and
      variations in the peak heights of Ca(2+). In addition, we find for one model that
      there is a distribution of latency times, rather than a single latency time, with
      a distribution width which is comparable to the experimental observation of spike
      widths. We also find for the other model with low gap junction diffusion that it
      is possible for cell multiplets to oscillate independently initially, but to
      subsequently become synchronized.

PMID- 11527451
TI  - The art of listening.

PMID- 11527452
TI  - Patient positioning and spinal locking for lumbar spine rotation manipulation.
AB  - High velocity low amplitude (HVLA) thrust techniques are widely used by many
      manual therapists to treat low back pain. There is increasing evidence that
      spinal manipulation produces positive patient outcomes for acute low back pain.
      HVLA thrust techniques are associated with an audible release in the form of a
      pop or cracking sound that is widely accepted to represent cavitation of a spinal
      zygapophyseal joint. This audible release distinguishes these techniques from
      other manual therapy interventions. When using long lever HVLA thrust techniques
      spinal locking is necessary to localize forces and achieve cavitation at a
      specific vertebral segment. A critical factor in applying lumbar spine
      manipulation with minimal force is patient positioning and spinal locking. A
      knowledge of coupled movements of the lumbar spine aids an understanding of the
      patient positioning required to achieve spinal locking consistent with maximal
      patient comfort and cooperation. Excessive rotation can result in pain, patient
      resistance and failed technique. This masterclass presents a model of patient
      positioning for the lumbar spine that minimizes excessive use of rotation to
      achieve spinal locking prior to the application of the thrust.

PMID- 11527453
TI  - The influence of initial resting posture on range of motion of the lumbar spine.
AB  - The aim of this study was to investigate the influence of initial resting posture
      on range of motion of the lumbar spine in 18 normal subjects. Subjects resting
      posture and active range of motion was measured using the CA-6000 Spinal Motion
      Analyser (OSI, USA) in five test positions, namely in flat standing and with a
      variety of heel raises. Analysis showed that there was no significant correlation
      between subject's normal resting posture and active range of motion. However,
      when subjects resting posture was artificially altered with heel raises,
      significant effects on the active range of motion were demonstrated. Increasing
      heel height significantly influenced resting posture in the sagittal plane only.
      As heel height increased, the lumbar lordosis decreased and a significant
      reduction in the range of lumbar spine flexion (P<0.001) was observed. Simulating
      pelvic asymmetry influenced resting posture in the frontal plane and significant
      effects on the range of lateral flexion (P<0.05) were observed. These results
      have important clinical implications in terms of using range of motion of the
      lumbar spine as an examination tool and suggest that studies using range of
      motion as an outcome measure should consider initial resting posture.

PMID- 11527454
TI  - Intra-operator and inter-operator reliability of surface electromyography in the
      clinical evaluation of back muscles.
AB  - As a prerequisite to the use of a test battery based on electromyographic (EMG)
      analysis of the paraspinal muscles for identifying and remedying back muscle
      dysfunction, the intra- and inter-operator reliability was assessed. Fifteen
      volunteers underwent EMG tests on three occasions. The test subjects were asked
      to perform 22 exercises, subdivided into four categories: coordination,
      stabilization, balance and strength exercises. The time interval between the
      tests was one week. The myoelectric signals of the multifidus (MF) and
      iliocostalis lumborum pars thoracis (ICLT) were analysed with regard to amplitude
      (averaged EMG) and frequency (zero cross rate). The results indicated that the
      reliability was better for the MF than for the ICLT, and also for exercises at
      higher loads (strength exercises). In the intra-operator condition, the
      reproducibility of the averaged EMG was good (ICC>0.75), except for the balance
      exercises (ICC = 0.40-0.74). In general, the averaged EMG in the inter-operator
      condition and the zero cross rate in both the intra- and inter-operator
      conditions are less or poorly reliable. These results demonstrate that when back
      muscle function is evaluated during coordination, stabilization and strength
      exercises, only the averaged EMG parameter has acceptable reproducibility over
      time when assessed by the same operator.

PMID- 11527455
TI  - Pain and muscular responses to a neural tissue provocation test in the upper
      limb.
AB  - Pain and muscular responses to a Neural Tissue Provocation Test with bias to
      median nerve were examined in 20 asymptomatic subjects. The test was performed on
      both arms with the cervical spine in a neutral position and in contralateral
      sideflexion as a sensitizing manoeuvre. The angle of elbow extension at the time
      of onset of pain and muscle activity in trapezius, biceps and triceps muscles was
      measured using an electrogoniometer. Muscle activity was recorded by surface
      electromyography. Results indicate that pain responses and muscle activity of
      trapezius are present in the majority of normal subjects. The onset of pain was
      highly reliable and compared favourably with detection of muscle activity onset.
      There was no significant difference of the angle of the elbow with the onset of
      pain between arms. Hence in patients with unilateral neck or upper limb pain a
      difference between sides might be indicative of a possible neural tissue
      involvement. Pain and muscular responses were influenced by the position of the
      cervical spine. This finding suggests that cervical contralateral sideflexion has
      a sensitizing effect on neural tissues. There was an association between the
      onset of pain and onset of trapezius muscle activity in all painful trials.
      However, muscle activity was also present in subjects with no pain.

PMID- 11527456
TI  - The initial effects of an elbow mobilization with movement technique on grip
      strength in subjects with lateral epicondylalgia.
AB  - This preliminary study indicates the proportion of patients with lateral
      epicondylalgia that demonstrate a favourable initial response to a manual therapy
      technique - the mobilization with movement (MWM) for tennis elbow. Twenty-five
      subjects with lateral epicondylalgia participated. In a one-group pretest - post
      test design, we measured (1) pain with active motion, (2) pain-free grip strength
      and, (3) maximum grip strength before and after a single intervention of MWM.
      Results of the study indicate that MWM was effective in allowing 92% of subjects
      to perform previously painful movements pain-free, and improving grip strength
      immediately afterwards. Significant differences were found between the grip
      strength of the affected and unaffected limbs prior to the intervention. Both
      pain-free grip strength and maximum grip strength of the affected limb increased
      significantly following the intervention. Pain-free grip strength increased by a
      greater magnitude than maximum grip strength. It can be concluded that MWM is a
      promising intervention modality for the treatment of patients with Lateral
      Epicondylalgia. Pain-free grip strength is a more responsive measure of outcome
      than maximum grip strength for patients with Lateral Epicondylalgia. Further
      research is warranted to investigate the long-term effectiveness of MWM in the
      treatment of impairment and disability resulting from Lateral Epicondylalgia.

PMID- 11527457
TI  - Mobilization with movement applied to the elbow affects shoulder range of
      movement in subjects with lateral epicondylalgia.
AB  - Clinical observations have suggested a relationship between shoulder range of
      movement (ROM) and lateral epicondylalgia. This study reports the effect of a
      single intervention of a mobilization with movement (MWM) applied to the elbow,
      on shoulder rotation ROM in subjects with lateral epicondylalgia. Twenty-three
      subjects with lateral epicondylalgia were included. In a one-group pretest-post
      test design, ROM of shoulder internal and external rotation were measured by
      goniometer before and after the application of the MWM, of both the unaffected
      and the affected limbs. Significant differences in pre-intervention external
      rotation ROM were found between unaffected and affected shoulders of subjects
      with lateral epicondylalgia, but no significant difference remained post
      intervention. It may be concluded that restriction of shoulder rotation ROM is
      present in patients with lateral epicondylalgia, probably due to a facilitated
      level of shoulder rotator muscle tone. Shoulder internal and external rotation
      ROM increases significantly following MWM to the elbow, in subjects with
      unilateral lateral epicondylalgia. Surprisingly, these ROM increases are also
      apparent on the 'unaffected' limb. These findings suggest that the MWM causes a
      neurophysiologically mediated decrease in resting muscle tone.

PMID- 11527458
TI  - Traumatic thumb injury management using mobilization with movement.

PMID- 11527459
TI  - Bibliography. Musculoskeletal pain.

PMID- 11527461
TI  - Phylogenetic relationships among higher Nemertean (Nemertea) Taxa inferred from
      18S rDNA sequences.
AB  - We estimated the phylogenetic relationships of 15 nemertean (phylum Nemertea)
      species from the four subclasses Hoplo-, Hetero-, Palaeo-, and Bdellonemertea
      with 18S rDNA sequence data. Three outgroup taxa were used for rooting: Annelida,
      Platyhelminthes, and Mollusca. Parsimony and maximum-likelihood analyses
      supported the monophyletic status of the Heteronemertea and a taxon consisting of
      hoplonemerteans and Bdellonemertea, while indicating that Palaeonemertea is
      paraphyletic. The monophyletic status of the two nemertean classes Anopla and
      Enopla is not supported by the data. The unambiguous clades are well supported,
      as assessed by a randomization test (bootstrapping) and branch support values.

PMID- 11527463
TI  - Can microsatellites be used to infer phylogenies? Evidence from population
      affinities of the Western Canary Island lizard (Gallotia galloti).
AB  - Population phylogeographic studies are generally based solely on mtDNA without
      corroboration, from an independent segregating unit (i.e., nuclear genes), that
      the mtDNA gene tree represents the organismal phylogeny. This paper attempts to
      evaluate the utility of microsatellites for this process by use of the Western
      Canary Island lacertid (Gallotia galloti) as a model. The geological times of
      island eruptions are known, and well-supported mtDNA phylogenies exist
      (corroborated as the organismal phylogeny rather than just a gene tree by nuclear
      random amplified polymorphic DNAs (RAPDs)). The allelic variation in 12
      populations from four islands (representing five haplotype lineages) was
      investigated in five unlinked microsatellite loci. Analysis of molecular variance
      showed this data to be highly structured. A series of genetic distances among
      populations was computed based on both the variance in allele frequency (i.e.,
      F(st) related) and the variance in repeat numbers (i.e., R(st) related). The
      genetic distances based on the former were more highly correlated with the mtDNA
      genetic distances than those based on the latter. All trees based on both models
      supported the primary division shown by mtDNA and RAPDs, which is dated at ca.
      2.8 to 5.6 mybp (depending on calibration of the mtDNA clock) and which could,
      under the evolutionary species concept, be regarded separate species. This was
      achieved despite theoretical problems posed by the use of few loci, suspected
      bottlenecks, and large population sizes. The finer details were less consistently
      represented. Nevertheless, this study demonstrates that even a small number of
      microsatellites can be useful in corroborating the deeper divisions of a
      population phylogeny.

PMID- 11527462
TI  - Molecular phylogeny of the chipmunks inferred from Mitochondrial cytochrome b and
      cytochrome oxidase II gene sequences.
AB  - There are currently 25 recognized species of the chipmunk genus Tamias. In this
      study we sequenced the complete mitochondrial cytochrome b (cyt b) gene of 23
      Tamias species. We analyzed the cyt b sequence and then analyzed a combined data
      set of cyt b along with a previous data set of cytochrome oxidase subunit II
      (COII) sequence. Maximum-likelihood was used to further test the fit of models of
      evolution to the cyt b data. Other sciurid cyt b sequence was added to examine
      the evolution of Tamias in the context of other sciurids. Relationships among
      Tamias species are discussed, particularly the possibility of a current sorting
      event among taxa of the southwestern United States and the extreme divergences
      among the three subgenera (Neotamias, Eutamias, and Tamias).

PMID- 11527464
TI  - Classification and phylogenetic relationships of African tilapiine fishes
      inferred from mitochondrial DNA sequences.
AB  - African cichlid fishes are composed of two major lineages, the haplochromines and
      the tilapiines. Whereas the phylogenetic relationships of the haplochromines have
      been studied extensively, primarily because of their spectacular adaptive
      radiations in the Great Lakes of East Africa, little is known about the
      relationships among the tilapiine species, despite the fact that they have become
      an important component of African, indeed world, aquaculture. To remedy this
      situation, molecular phylogenetic analysis of tilapiine fishes was undertaken. A
      segment of mitochondrial DNA encompassing the terminal part of the tRNA(Pro) gene
      and the most variable part of the control region was amplified by the polymerase
      chain reaction with DNA samples isolated from 42 tilapiine species, and the
      amplification products were subjected to heteroduplex analysis and sequencing.
      Phylogenetic trees based on 68 sequences revealed the existence of 11 sequence
      groups and 11 single-sequence branches. The groups, designated Ti1 through Ti11,
      were distinguished by specific combinations of diagnostic substitutions,
      formation of monophyletic clusters, and separation by genetic distances in excess
      of 0.04. Although the relationships among the groups could not be resolved, the
      sequences separated Oreochromis and Sarotherodon from Tilapia, as defined by
      Trewavas. The Oreochromis sequences clustered with the Sarotherodon sequences and
      thus supported the hypothesis that the mouthbrooding behavior of the tilapiine
      fishes evolved only once from the substrate-spawning behavior. Since on
      phylogenetic trees the O. alcalicus (sub)species were always separated from O.
      amphimelas by other Oreochromis species, it was concluded that the adaptation to
      life in water with a high salt concentration and high pH values evolved
      independently at least twice in the tilapiine fishes. The tilapiines diverged
      from the haplochromines more than 8 million years ago; most of the intragroup
      divergences among the tilapiines took place an estimated 1.1 to 6 million years
      ago.

PMID- 11527465
TI  - Evidence for three major clades within the snapping shrimp genus Alpheus inferred
      from nuclear and mitochondrial gene sequence data.
AB  - The snapping shrimp genus Alpheus is among the most diverse of caridean shrimps,
      and analyses of taxa separated by the Isthmus of Panama have been used to
      estimate rates of molecular evolution. Although seven morphological groups have
      been informally suggested, no formal phylogenetic analysis of the genus has been
      previously attempted. Here we infer the phylogenetic relationships within Alpheus
      using sequence data from two nuclear genes, glucose-6-phosphate isomerase and
      elongation factor-1alpha, and from the mitochondrial gene cytochrome oxidase I.
      Three major clades corresponding to previously noted morphological features were
      identified. Discrepancies between earlier informal morphological groupings and
      molecular analyses largely consisted of species whose morphologies were not
      entirely typical of the group to which they had been assigned. The traditional
      placements of shrimp with highly sessile lifestyles and consequently simplified
      morphologies were also not supported by molecular analyses. Phylogenies for
      Alpheus suggest that specialized ecological requirements (e.g., symbiotic
      associations and estuarine habitats) and modified claw morphologies have evolved
      independently several times. These new analyses also support the sister species
      status of transisthmian pairs analyzed previously, although very similar pairs
      were not always resolved with the more slowly evolving nuclear loci. In addition,
      six new cryptic species were identified in the course of these studies plus a
      seventh whose status remains to be determined.

PMID- 11527466
TI  - Molecular phylogeny of gobioid fishes (Perciformes: Gobioidei) based on
      mitochondrial 12S rRNA sequences.
AB  - The molecular phylogeny of the gobioid fishes, comprising 33 genera and 43 valid
      species, was examined by use of complete mitochondrial 12S rRNA and
      tRNA(VAL)genes. Both parsimony and neighbor-joining analyses revealed comparable
      results and are generally congruent with those of morphological studies. The
      Odontobutis, which was always placed at the base of the phylogenetic trees, can
      be treated as a sister group of all other nonrhyacichthyid gobioids. Within
      eleotrid fishes, the monophyly of the Eleotrinae is strongly supported by
      molecular data. The Butinae is closer to fishes with five branchiostegal rays and
      should be treated as a sister group of the latter. The group with five
      branchiostegal rays, except for sicydiines, can be divided into two groups
      according to their epural counts. Fish with one epural, the Gobiinae of Pezold
      plus Microdesmidae, form a monophyletic group which is sister to those with two
      epurals, the Oxudercinae and Gobionellinae of Pezold. However, Sicydiinae, which
      have one epural, are closer to the Oxudercinae and Gobionellinae rather than to
      the Gobiinae. Since progressive reduction in epural number has been observed
      along this lineage, the sicydiines should be treated as a derived group within
      the groups with two epurals.

PMID- 11527467
TI  - Retrieval of four adaptive lineages in duiker antelope: evidence from
      mitochondrial DNA sequences and fluorescence in situ hybridization.
AB  - Independent molecular markers (mitochondrial DNA sequences from two genes and
      fluorescence in situ hybridization with satellite DNA sequences as hybridization
      probes) were employed to investigate phylogenetic relationships among duiker
      antelope. When analyzed singly or taken together, the molecular and cytogenetic
      data allowed for the delimitation of four adaptive groups: the conservative
      dwarfs which are basal, a savanna specialist which groups apart from the forest
      duikers, the giant duikers, and the red duikers. Within the latter, a further
      subdivision comprising an east African and a west African red duiker clade is
      evident. The placement of the endangered zebra duiker and Aders' duiker remains
      problematic. Several of the nomenclatural divisions in current use are questioned
      by our results. These include the recognition of Philantomba as genus name for
      the blue and Maxwell's duiker and that Harvey's duiker be relegated to a
      subspecies of the Natal red duiker. We place our results in a biogeographic
      context and argue that duiker speciation has been driven predominantly by habitat
      fragmentation which probably led to the disruption of gene flow between
      geographic populations.

PMID- 11527468
TI  - Molecular systematics of the family Mormoopidae (Chiroptera) based on cytochrome
      b and recombination activating gene 2 sequences.
AB  - We examined 1140 bp of the mitochondrial cytochrome b gene and 1398 bp of the
      nuclear RAG2 gene to investigate the systematics of the eight species of bats
      within the family Mormoopidae. It was concluded that within the genus Pteronotus
      there were four valid subgenera: Phyllodia, Chilonycteris, Pteronotus, and an
      undescribed subgenus. Within Pteronotus, P. parnellii either was part of an
      unresolved tetratomy with the other three subgenera (cytochrome b data) or was
      basal (RAG2 and combined data). For three species, P. gymnonotus, P. macleayii,
      and P. quadridens, our sample revealed little geographic variation. In P. davyi
      and P. parnellii, the magnitude of genetic distance suggests the possibility of
      two biological species existing within the currently recognized taxa. Within P.
      personatus, there was substantial geographic variation partitioned in a step-like
      fashion among our specimens. Neither of the species within the genus Mormoops
      showed the deep distance nodes present in P. davyi, P. parnellii, and P.
      personatus. Cytochrome b and RAG2 data indicated that M. megalophylla evolved
      recently from its common ancestor. Although there was considerable agreement
      among the branching patterns for the nuclear and mitochondrial genes, both genes
      failed to provide robust data concerning the evolutionary relationships among the
      subgenera.

PMID- 11527469
TI  - Molecular systematics of aphids and their primary endosymbionts.
AB  - Aphids constitute a monophyletic group within the order Homoptera (i.e.,
      superfamily Aphidoidea). The Aphidoidea originated in the Jurassic about 150 my
      ago from some aphidiform ancestor whose origin can be traced back to about 250 my
      ago. They exhibit a mutualistic association with intracellular bacteria (Buchnera
      sp.) related to Escherichia coli. Buchnera is usually considered the aphids'
      primary endosymbiont. The association is obligate for both partners. The 16S rDNA
      based phylogeny of Buchnera from four aphid families showed complete concordance
      with the morphology-based phylogeny of their aphid hosts, which pointed to a
      single original infection in a common ancestor of aphids some 100-250 my ago
      followed by cospeciation of aphids and Buchnera. This study concentrated on the
      molecular phylogeny of both the aphids and their primary endosymbionts of five
      aphid families including for the first time representatives of the family
      Lachnidae. We discuss results based on two Buchnera genes (16S rDNA and the beta
      subunit of the F-ATPase complex) and on one host mitochondrial gene (the subunit
      6 of the F-ATPase complex). Although our data do not allow definitive
      evolutionary relationships to be established among the different aphid families,
      some traditionally accepted groupings are put into question from both bacterial
      and insect data. In particular, the Lachnidae and the Aphididae, which from
      morphological data are considered recently evolved sister groups, do not seem to
      be as closely related as is usually accepted. Finally, we discuss our results in
      the light of the proposed parallel evolution of aphids and their endosymbionts.

PMID- 11527470
TI  - Molecular phylogeny and evolution of the freshwater eel, genus Anguilla.
AB  - A molecular phylogenetic analysis was conducted on all of the known catadromous
      eel species of the genus Anguilla to assess their relationships and evolutionary
      history. The analyses of a total of 1427 bp of the mitochondrial 16S ribosomal
      RNA and 1140 bp of the complete cytochrome b gene sequences suggested that the
      genus Anguilla was monophyletic in origin, with A. borneensis as the most basal
      species. Four clades/species groups that correspond to their geographical ranges
      were indicated, Indo-Atlantic (three species), Oceania (two species), tropical
      Pacific (two species), and Indo-Pacific (five species), with ambiguous positions
      for A. japonica and A. reinhardti. This grouping conflicts with that of a
      previous morphological study, since the broad undivided maxillary and short-fin
      type, which were thought to be phylogenetically important, were paraphyletic in
      the molecular analysis. However, the molecular phylogeny and the present
      geographic distribution of species suggested historical dispersion of the genus
      Anguilla according to the Tethys corridor hypothesis, which proposed that
      anguillid eels originated near present-day Indonesia and dispersed westward along
      paleo-circumglobal equatorial currents. The westward-moving strain entered the
      paleo-Atlantic through the Tethys Sea and was ancestral to present-day European
      and American species.

PMID- 11527471
TI  - Examining monophyly in a large radiation of Madagascan butterflies (Lepidoptera:
      Satyrinae: Mycalesina) based on mitochondrial DNA data.
AB  - The satyrine butterfly subtribe Mycalesina has undergone one of the more
      spectacular evolutionary radiations of butterflies in the Old World tropics.
      Perhaps the most phenotypically pronounced diversification of the group has
      occurred in the Malagasy region, where 68 currently recognized species are
      divided among five genera. Here, we report the results of phylogenetic analyses
      of sequence data from the cytochrome c oxidase II and cytochrome b mitochondrial
      genes, for a total of 54 mycalesine taxa, mostly from Madagascar. These molecular
      data complement an existing data set based on male morphological characters. The
      molecular results support the suggestion from morphology that three of the five
      Malagasy genera are paraphyletic and support the monophyly of at least three
      major morphological clades. Novel hypotheses of terminal taxon pairs are
      generated by the molecular data. Dense taxon sampling appears to be crucial for
      elucidating phylogenetic relationships within this large radiation. A potentially
      complex scenario for the origin of Malagasy mycalesines is proposed.

PMID- 11527472
TI  - Inferring the history of the polyploid Silene aegaea (Caryophyllaceae) using
      plastid and homoeologous nuclear DNA sequences.
AB  - The origin of the rare allotetraploid Silene aegaea was inferred from plastid
      rps16 intron sequences, homoeologous copies of nuclear ribosomal internal
      transcribed spacer (ITS) sequences, and an intron from the nuclear gene coding
      for the second largest subunit of RNA polymerase II (RPB2). The nuclear DNA
      regions support the S. sedoides and S. pentelica lineages as most closely related
      to the two S. aegaea paralogues. A few recombinant ITS sequences were found, but
      as PCR recombination could be demonstrated, no true recombination could be
      demonstrated. No recombination was found in the RPB2 sequences. Plastid rps16
      intron sequences strongly support S. pentelica as the maternal lineage. The
      strength of the approach of using homoeologous sequences of several loci is
      demonstrated, and its usefulness for the study of phylogenies of groups including
      polyploids is emphasized.

PMID- 11527474
TI  - Growth hormone administration and exercise effects on muscle fiber type and
      diameter in moderately frail older people.
AB  - OBJECTIVE: Reduced muscle mass and strength are characteristic findings of growth
      hormone deficiency (GHD) and aging. We evaluated measures of muscle strength,
      muscle fiber type, and cross sectional area in response to treatment with
      recombinant human growth hormone (rhGH) with or without a structured resistance
      exercise program in frail older subjects. DESIGN: Placebo-controlled, randomized,
      double blind trial. SETTING: Outpatient clinical research center at an urban
      university-affiliated teaching hospital. PARTICIPANTS: Thirty-one consenting
      older subjects (mean age 71.3 +/- 4.5 years) recruited as a subset of a larger
      project evaluating rhGH and exercise in older people, who underwent 62 quadricep
      muscle biopsies. INTERVENTION: Random assignment to a 6-month course of one of
      four protocols: rhGH administered subcutaneously daily at bedtime, rhGH and a
      structured resistance exercise program, structured resistance exercise with
      placebo injections, or placebo injections only. MEASUREMENTS: Muscle biopsy
      specimens were obtained from the vastus lateralis muscle. Isokinetic dynamometry
      strength tests were used to monitor individual progress and to adjust the weights
      used in the exercise program. Serum insulin-like growth factor-I (IGF-I) was
      measured and body composition was measured using a Hologic QDR 1000W dual X-ray
      densitometer. RESULTS: The administration of rhGH resulted in significant
      increase in circulating IGF-I levels in the individuals receiving rhGH treatment.
      Muscle strength increased significantly in both the rhGH/exercise (+55.6%, P
      =.0004) as well as the exercise alone (+47.8%, P =.0005) groups. There was a
      significant increase in the proportion of type 2 fibers between baseline and six
      months in the combined rhGH treated subjects versus those not receiving rhGH (P
      =.027). CONCLUSIONS: Our results are encouraging in that they suggest an effect
      of growth hormone on a specific aging-correlated deficit. IGF-I was increased by
      administrating rhGH and muscle strength was increased by exercise. The
      administration of rhGH to frail older individuals in this study resulted in
      significant changes in the proportions of fiber types. Whether changes in fiber
      cross-sectional area or absolute number occur with long-term growth hormone
      administration requires further study.

PMID- 11527475
TI  - A randomized trial of exercise programs among older individuals living in two
      long-term care facilities: the FallsFREE program.
AB  - OBJECTIVE: To use two different exercise programs over a 2-year period to reduce
      falls and their sequelae among residents of two long-term care facilities.
      DESIGN: Randomized, controlled trial. SETTING: The study took place at two long
      term care facilities with services ranging from independent living to skilled
      nursing. PARTICIPANTS: One hundred and ten participants whose average age was 84
      and who were capable of ambulating with or without assistive devices and could
      follow simple directions. INTERVENTION: Participants were randomized to one of
      two exercise groups (resistance/endurance plus basic enhanced programming or tai
      chi plus basic enhanced programming) or to a control group (basic enhanced
      programming only). Exercise classes were held three times per week throughout the
      study. MEASUREMENTS: Participants were evaluated for cognitive and physical
      functioning at baseline and 6, 12, and 24 months. Falls were determined from
      incident reports filed by the nursing staffs at the facilities. RESULTS: Time to
      first fall, time to death, number of days hospitalized, and incidence of falls
      did not differ among the treatment and control groups (P>.05). Among all
      participants, those who fell had significantly lower baseline Folstein Mini
      Mental State Examination and instrumental activities of daily living scores and
      experienced significantly greater declines in these measures over the 2-year
      program. CONCLUSION: There were no significant differences in falls among the two
      exercise groups and the control group. Lack of treatment differences and low
      adherence rates suggest that residents of long-term care facilities may require
      individualized exercise interventions that can be adapted to their changing
      needs.

PMID- 11527476
TI  - Deriving a risk-adjustment model for pressure ulcer development using the Minimum
      Data Set.
AB  - OBJECTIVE: To use the Minimum Data Set (MDS) to derive a risk-adjustment model
      for pressure ulcer development that may be used in assessing the quality of
      nursing home care. DESIGN: Perspective observational study using MDS data from
      1997. SETTING: A large, for-profit, nursing home chain. PARTICIPANTS: Our unit of
      analysis was 39,649 observations made on 14,607 nursing home residents who were
      without a stage 2 or larger pressure ulcer on an index assessment. MEASUREMENTS:
      Pressure ulcer status was determined at an outcome assessment approximately 90
      days after an index assessment. Potential predictors of pressure ulcer
      development were examined for bivariate associations, contributing to the
      development of a multivariate logistic regression model. RESULTS: A stage 2 or
      larger pressure ulcer developed in 2.3% of the observations. Seventeen resident
      characteristics were found to be associated with pressure ulcer development.
      These included dependence in mobility and transferring, diabetes mellitus,
      peripheral vascular disease, urinary incontinence, lower body mass index, and end
      stage disease. A risk-adjustment model based on these characteristics was well
      calibrated and able to discriminate among residents with different levels of risk
      for ulcer development (model c-statistic = 0.73). CONCLUSION: A clinically
      credible risk-adjustment model with good performance properties can be developed
      using the MDS. This model may be useful in profiling nursing homes on their rate
      of pressure ulcer development.

PMID- 11527477
TI  - Evaluation of a risk-adjustment model for pressure ulcer development using the
      Minimum Data Set.
AB  - OBJECTIVE: To validate a previously derived risk-adjustment model for pressure
      ulcer development in a separate sample of nursing home residents and to determine
      the extent to which use of this model affects judgments of nursing home
      performance. DESIGN: Retrospective observational study using Minimum Data Set
      (MDS) data from 1998. SETTING: A large, for-profit, nursing home chain.
      PARTICIPANTS: Twenty-nine thousand and forty observations were made on 13,457
      nursing home residents who were without a pressure ulcer on an index assessment.
      MEASUREMENTS: We used logistic regression in our validation sample to calculate
      new coefficients for the 17 previously identified predictors of pressure ulcer
      development. Coefficients from this new sample were compared with those
      previously derived. Expected rates of pressure ulcer development were determined
      for 108 nursing homes. Unadjusted and risk-adjusted rates of pressure ulcer
      development from these homes were also calculated and outlier identification
      using these two approaches was compared. RESULTS: Predictors of pressure ulcer
      development in the derivation sample generally showed similar effects in the
      validation sample. The model c-statistic was also unchanged at 0.73, but it was
      not calibrated as well in the validation sample. On applying the model to the
      nursing homes, expected rates of ulcer development ranged from 1.1% to 3.2% (P
      <.001). The observed rates ranged from 0% to 12.1% (P <.001). There were 12
      outliers using unadjusted rates and 15 using adjusted performance. Ten nursing
      homes were identified as outliers using both approaches. CONCLUSIONS: Our MDS
      risk-adjustment model for pressure ulcer development performed well in this new
      sample. Nursing homes differ significantly in their expected rates of pressure
      ulcer development. Outlier identification also differs depending on whether
      unadjusted or risk-adjusted performance is evaluated.

PMID- 11527478
TI  - Serum and urine markers of bone metabolism during the year after hip fracture.
AB  - OBJECTIVE: As part of a larger study to describe indices of recovery during the
      year after hip fracture, the current prospective study investigated longitudinal
      changes in serum and urine markers of bone metabolism for the year after hip
      fracture and related them to bone mineral density (BMD). DESIGN: A representative
      subset of participants provided serum and urine samples and had bone density
      measured at 3, 10, 60, 180, and 365 days postfracture. SETTING: Two Baltimore
      hospitals. PARTICIPANTS: The subjects were 205 community-dwelling, white women
      age 65 and older with fresh proximal femur fractures. MEASUREMENTS: Samples were
      assayed for specific bone-related proteins and bone turnover markers, including
      serum osteocalcin (OC), procollagen type 1 carboxy-terminal extension peptide
      (PICP), bone-specific alkaline phosphatase (BAP), and urinary deoxypyridinoline
      (DPD) cross-links. Selected hormonal regulators of bone metabolism, including
      parathyroid hormone (PTH), calcitonin (CT), 1,25-dihydroxy vitamin D(3) (1,25
      (OH)(2)D), and estrone (E(1)) were measured from serum samples. Repeated measures
      analyses were used to evaluate postfracture changes in each of the markers.
      RESULTS: BAP, OC, and PICP were most active during the early postfracture period
      (3-60 days). BAP and OC remained elevated at 365 days compared with 3 days. DPD
      rose 48% from 3 days to 60 days, but this difference was not statistically
      significant. PTH and 1,25 (OH)(2)D increased steadily and significantly from 3 to
      365 days. E(1) was highest at baseline and decreased at each time point, whereas
      CT showed no significant changes. When subjects were stratified into high-,
      medium-, and low-BMD groups based on their measurement at 3 days, both
      osteoclastic and osteoblastic markers in the low-BMD group displayed exaggerated
      and different patterns over time compared with the other groups. CONCLUSION:
      Currently, the standard treatment of care for hip fractures still results in high
      morbidity and mortality and failure to regain prefracture quality of life.
      Gaining an understanding of bone cell activity in these patients after hip
      fracture, derived by measuring markers longitudinally during recovery, provides a
      baseline by which to measure the effectiveness of new interventions to improve
      recovery from hip fracture.

PMID- 11527479
TI  - Strength, balance, and the modifying effects of obesity and knee pain: results
      from the Observational Arthritis Study in Seniors (oasis).
AB  - OBJECTIVE: To examine the relationship between muscular strength and dynamic
      balance in a sample of older adults with knee pain and to determine the role that
      obesity and severity of knee pain play in the ability to maintain balance.
      DESIGN: Cross-sectional study designed to examine the association between
      strength and balance in a cohort of older adults with chronic knee pain. SETTING:
      A university health and exercise science center. PARTICIPANTS: A cohort of 480
      adults age 65 and older with knee pain. MEASUREMENTS: Force platform dynamic
      balance measure of the center of pressure excursion during a forward and
      subsequent backward lean. Isokinetic strength measures of concentric and
      eccentric knee flexion and extension and concentric ankle plantar flexion and
      dorsiflexion. Body mass index (BMI) and a knee pain scale were used to measure
      obesity and knee pain, respectively. RESULTS: A regression model was developed to
      investigate the relationship between dynamic balance and muscular strength while
      controlling for gender, BMI, radiographic severity, knee pain, and foot length.
      Knee strength alone explained 18.4% of the variability in dynamic balance. The
      addition of knee pain, BMI, radiographic severity, gender, and foot length
      explained an additional 6.7%. When the knee-ankle interaction, ankle strength,
      and knee strength--pain interaction variables were added to the regression model,
      28.9% of the variability in dynamic balance was explained. CONCLUSIONS: Strength
      appears to play a significant role in maintaining balance in an older,
      osteoarthritic population. We found that mean knee strength accounted for
      approximately 19% of the variability in dynamic balance. Hence, greater knee
      strength was associated with better dynamic balance. The best dynamic balance
      performances occurred in participants that had a combination of strong knees and
      strong ankles. However, knee osteoarthritic patients with weak knee strength
      could still maintain high levels of dynamic balance by having strong ankle
      strength. Moreover, we have shown that obesity is associated with attenuated
      dynamic balance performance and that poorer balance is associated with higher
      pain scores in the presence of weaker knees. For stronger knees, however, pain
      does not appear to be related to balance.

PMID- 11527480
TI  - Self-reported social and emotional impact of urinary incontinence.
AB  - OBJECTIVE: Incontinence-specific and generic measures of well-being were
      regressed on potential predictors to identify incontinent respondents at risk for
      psychosocial distress and to understand the relationship between urinary
      incontinence (UI) and other determinants of social and emotional status. DESIGN:
      Survey data were collected May 1994 through April 1996. SETTING: Telephone
      interviews as a supplement to a nationally representative monthly consumer
      survey. PARTICIPANTS: Analyses were based on 1,116 continent and 206 incontinent
      respondents age 40 and older. MEASUREMENTS: Incontinent respondents self-reported
      the extent to which urine loss restricted social activities or affected their
      feelings about themselves. All respondents were asked whether they felt
      depressed, lonely, or sad. Covariates included sex, age, race, education, social
      desirability, health status, frequency of urine loss, quantity of loss, and
      urgency. RESULTS: The majority of incontinent respondents reported that urine
      loss did not restrict activities or diminish self-esteem. Incontinent respondents
      who were younger, male, less educated, lower in social desirability, in poorer
      health, or losing greater quantities of urine were more likely to report
      psychosocial distress, although these correlates were not consistently
      significant. Compared with continent respondents, significantly higher
      percentages of incontinent respondents reported feeling depressed, lonely, or
      sad. In the multivariate models, incontinence retained an independent association
      with loneliness, but not with sadness or depression. CONCLUSION: Even though the
      direct psychosocial impact of urine loss may be minor in many cases, UI is
      associated with a constellation of physical and behavioral factors that can
      impose a social and emotional burden. This suggests that UI cannot be adequately
      evaluated or treated without consideration of the patient's overall quality of
      life.

PMID- 11527481
TI  - Healthy centenarians do not exist, but autonomous centenarians do: a population
      based study of morbidity among Danish centenarians.
AB  - OBJECTIVE: To assess the prevalence of common illnesses in an unselected
      population of centenarians. DESIGN: A population-based survey. SETTING: Denmark.
      PARTICIPANTS: All Danes who celebrated their 100th anniversary between April 1,
      1995 and May 31, 1996: 276 persons. MEASUREMENTS: All participants (including
      proxies) were visited at their domicile for an interview (sociodemographic
      characteristics, activities of daily living, living conditions, need of
      assistance from other people, former health and current diseases, current
      medication) and a clinical examination (dementia screening test, heart and lung
      auscultation, neurological assessment, height and weight, electrocardiogram, arm
      and ankle blood pressure, assessment of hearing and vision capacity, a short
      physical performance test, bio-impedance, lung function test, blood test).
      Further health information was retrieved from medical files and national health
      registers. RESULTS: Seventy-five percent (207) of eligible subjects participated
      in the study. Cardiovascular disease was present in 149 (72%) subjects.
      Osteoarthritis (major joints) was present in 54%, hypertension (> or =140/ > or
      =90) in 52%, dementia in 51%, and ischemic heart disease in 28%. The mean number
      of illness was 4.3 (standard deviation (SD) 1.86). Only one subject was
      identified as being free from any chronic condition or illness. Sixty percent had
      been treated for illness with high mortality. In 25 autonomous (nondemented,
      functioning well physically, living at home) and 182 nonautonomous centenarians,
      comorbidities were equivalent. CONCLUSION: Because they have a high prevalence of
      several common diseases and chronic conditions, Danish centenarians are not
      healthy. However, a minor proportion was identified as being cognitively intact
      and functioning well.

PMID- 11527482
TI  - Disability in the oldest old: "can do" or "do do"?
AB  - OBJECTIVE: To investigate the discrepancies between outcomes for competence (can
      do) and actual performance (do do) in activities of daily living (ADLs). DESIGN:
      Baseline measurements of a population-based follow-up study. SETTING: Leiden 85
      Plus Study, the Netherlands. PARTICIPANTS: Five hundred and ninety-nine persons,
      age 85. The response rate was 86%. MEASUREMENTS: Face-to-face interviews.
      Measurements of competence and actual performance were based on the Groningen
      Activity Restriction Scale. Help received was assessed for several domains.
      Prevalence rates for disability were assessed according to the concepts of both
      competence and actual performance. Analysis was performed separately for basic
      activities of daily living (BADLs) and instrumental activities of daily living
      (IADLs). RESULTS: Seventy-seven percent of the oldest old were competent to
      perform all the BADLs and performed them regularly. Fifteen percent were not
      competent to perform certain BADLs independently but performed them regularly
      with help from others. The prevalence of disability defined as inability in one
      or more BADLs was 22% for women and 10% for men. The prevalence of disability
      defined as inactivity in one or more BADLs was 16% for women and 17% for men.
      Only 5% of the oldest old were competent to perform all IADLs and performed them
      regularly. In spite of being competent, 70% did not perform certain IADLs
      regularly. The prevalence of disability defined as inability in one or more IADLs
      was 64% for women and 55% for men. The prevalence of disability defined as
      inactivity in one or more IADLs was 92% for women and 98% for men. CONCLUSION:
      The structural discrepancies between the outcomes of competence and actual
      performance have important consequences when estimating disability in old people.
      Promoting actual performance in IADLs may reduce disability.

PMID- 11527483
TI  - The management of adverse clinical events in nursing homes: a 1-year survey
      study.
AB  - OBJECTIVE: In Italian nursing homes (NHs), care delivery at night and during
      holidays is not regulated by regional laws; some facilities employ staff
      physicians, others employ physicians engaged from year to year (temporary
      physicians), and others employ publicly funded National Health System (NHS)
      physicians. This study was designed to determine whether the use of different
      kinds of physicians leads to different outcomes with regard to the rate of
      hospitalization and appropriateness of the management of adverse clinical events.
      DESIGN: Prospective, nonrandomized-survey data collection. SETTING: Ten nonprofit
      nursing facilities in Italy. PARTICIPANTS: Three hundred and fifty-two NH
      residents, staff physicians, temporary physicians, and NHS physicians.
      MEASUREMENTS: Medical intervention during adverse clinical events occurring at
      night and during holidays. RESULTS: Three hundred and fifty-two residents
      experienced 551 adverse clinical events; 78 were hospitalized. The
      hospitalization rate of NHS physicians was about two times that of the temporary
      physicians and six times that of the staff physicians. Staff physicians'
      diagnoses and management were appropriate in the majority of cases; NHS diagnosis
      and management were doubtful or incorrect in about one-third of all cases.
      CONCLUSIONS: NH residents frequently experience adverse clinical events;
      physician characteristics influence the rate of hospitalization and the quality
      of medical interventions.

PMID- 11527484
TI  - An intervention to increase fluid intake in nursing home residents: prompting and
      preference compliance.
AB  - OBJECTIVE: To evaluate a three-phase, behavioral intervention to improve fluid
      intake in nursing home (NH) residents. DESIGN: Controlled clinical intervention
      trial. SETTING: Two community NHs. PARTICIPANTS: Sixty-three incontinent NH
      residents. INTERVENTION: Participants were randomized into intervention and
      control groups. The intervention consisted of three phases for a total of 32
      weeks: (1) 16 weeks of four verbal prompts to drink per day, in between meals;
      (2) 8 weeks of eight verbal prompts per day, in between meals; and (3) 8 weeks of
      eight verbal prompts per day, in between meals, plus compliance with participant
      beverage preferences. MEASUREMENTS: Between-meal fluid intake was measured in
      ounces by research staff during all three phases of the intervention. Percentage
      of fluids consumed during meals was also estimated by research staff for a total
      of nine meals per participant (3 consecutive days) at baseline and at 8 and 32
      weeks into the intervention. Serum osmolality, blood urea nitrogen, and
      creatinine values were obtained for all participants in one of the two sites at
      the same three time points. RESULTS: The majority (78%) of participants increased
      their fluid intake between meals in response to the increase in verbal prompts
      (phase 1 to 2). A subset of residents (21%), however, only increased their fluid
      intake in response to beverage preference compliance (phase 3). There was a
      significant reduction in the proportion of intervention participants who had
      laboratory values indicative of dehydration compared with the control
      participants. Cognitive and nutritional status were predictive of residents'
      responsiveness to the intervention. CONCLUSIONS: A behavioral intervention that
      consists of verbal prompts and beverage preference compliance was effective in
      increasing fluid intake among most of a sample of incontinent NH residents.
      Verbal prompting alone was effective in improving fluid intake in the more
      cognitively impaired residents, whereas preference compliance was needed to
      increase fluid intake among less cognitively impaired NH residents.

PMID- 11527485
TI  - Cognitive impairment and mortality in older primary care patients.
AB  - OBJECTIVE: To assess the impact of cognitive impairment on mortality in older
      primary care patients after controlling for confounding effects of demographic
      and comorbid chronic conditions. DESIGN: Prospective cohort study. SETTING:
      Academic primary care group practice. PARTICIPANTS: Three thousand nine hundred
      and fifty-seven patients age 60 and older who completed the Short Portable Mental
      Status Questionnaire (SPMSQ) during routine office visits. MEASUREMENTS:
      Cognitive impairment measured at baseline using the SPMSQ, demographics, problem
      drinking, history of smoking, clinical data (including weight, cholesterol level,
      and serum albumin), and comorbid chronic conditions collected at baseline;
      survival time measured during the 5 to 7 years after baseline. RESULTS: Eight
      hundred and eighty-six patients (22.4%) died during the 5 to 7 years of follow
      up. Cognitive impairment was categorized as having no impairment (84.3%), mild
      impairment (10.5%), and moderate-to-severe impairment (5.2%) based on SPMSQ
      score. Chi-square tests revealed that patients with moderate-to-severe impairment
      were significantly more likely to die compared with patients with mild impairment
      (40.8% vs 21.5%) and those with no impairment (40.8% vs 21.4%). No significant
      difference in crude mortality was found between patients with no impairment and
      those with mild impairment. After analyzing time to death using the Kaplan-Meier
      method, patients with moderate-to-severe cognitive impairment were at increased
      risk of death compared with those with no or mild impairment (Log-rank chi(2) =
      55.5; P <.0001). Even in multivariable analyses using Cox proportional hazards to
      control for confounding factors, compared with those with no impairment,
      moderately-to-severely impaired patients had an increased risk of death, with a
      hazard ratio (HR) of 1.70. Increased risk of death was also associated with older
      age (HR = 1.03 for each year), a history of smoking (HR = 1.48), having a serum
      albumin level <3.5 g/L (HR = 1.29), and weighing less than 90% of the ideal body
      weight (HR = 1.98). Outpatient diagnoses associated with increased mortality risk
      were diabetes mellitus, coronary artery disease, congestive heart failure,
      cerebrovascular disease, cancer, anemia, and chronic obstructive pulmonary
      disease (HR range 1.36-1.67). Factors protective of mortality risk included
      female gender (HR = 0.67) and black race (HR = 0.73). CONCLUSIONS: Moderate-to
      severe cognitive impairment is associated with an increased risk of mortality,
      even after controlling for confounding effects of demographic and clinical
      characteristics. Mild cognitive impairment is not associated with mortality risk,
      but a longer follow-up period may be necessary to identify this risk if it
      exists.

PMID- 11527486
TI  - Clock drawing: analysis in a retirement community.
AB  - OBJECTIVE: To test the hypothesis that performance on a clock-drawing test in a
      mailed survey to an older cohort is associated with known and potential risk and
      protective factors for Alzheimer's disease. DESIGN: The Leisure World Cohort
      Study is an ongoing study, begun in 1981, of nearly 14,000 older adults. In
      November 1992, the 8,406 living cohort members were mailed a follow-up
      questionnaire. SETTING: Leisure World Laguna Hills, a southern California
      retirement community. PARTICIPANTS: The study population is a predominantly
      white, well-educated, upper-middle-class community; approximately two-thirds are
      women. Data from 4,843 cohort members (mean age 80 years; range 52-101) were
      analyzed. MEASUREMENTS: The questionnaire included a clock-drawing task: a
      predrawn circle 3 1/4 inches (8.3 cm) in diameter was provided with instructions
      "In the circle below, draw in the numbers as on a clock face. Make no erasures."
      Clocks were scored on 7 items: all numbers 1-12 present without adding extra or
      omitting numbers, sequencing of numbers, position of numbers, orientation of
      numbers to circle, consistent number style (either Arabic or Roman), tilt of
      numbers, and superfluous marks. A total clock score was calculated by summing the
      number of correct individual items (0-7). We also classified individuals as
      cognitively impaired by a previously suggested method: individuals were affected
      if they did not have three numbers drawn in the upper left quadrant of the clock
      face. RESULTS: Ninety percent or more of the participants across all ages placed
      the numbers 1 to 12 on their clocks without omissions or additions; 35% completed
      the clock drawing without error. The mean total clock scores decreased with each
      successive 5-year age group in both men and women. Regression analysis indicated
      a significant effect for age (b = -0.15, P <.0001), education (b = 0.05, P
      =.0001), smoking (b = 0.13, P =.03), and female gender (b = -0.05, P =.05) and a
      marginally significant effect of nonrheumatoid arthritis (b = 0.05, P =.07) on
      total clock score. No other measured variable had a significant effect.
      Cognitively impaired individuals were more likely to be female and older. After
      adjusting for age and gender, they were also more likely to be hypertensive and
      to have taken blood pressure medication and less likely to be college graduates,
      have glaucoma or arthritis, and to have taken vitamin supplements. CONCLUSION:
      The clock-drawing task is an appealing measure of cognitive function for large
      epidemiological studies because it is a simple, self-administered test that is
      easily adapted to mail surveys and correlates with more-detailed and more-time
      consuming cognitive screens. Although it is relatively free of influence by
      language, cultural, or ethnic factors, our study shows that even in a highly
      educated population, clock drawing is influenced by educational level and other
      known risk factors for Alzheimer's disease. Thus a clock-drawing task may help
      predict cognitive frailty and future disability in older people. Such
      determination can direct high-risk individuals to earlier diagnosis, potential
      therapies, and better management.

PMID- 11527487
TI  - Acculturation and the prevalence of depression in older Mexican Americans:
      baseline results of the Sacramento Area Latino Study on Aging.
AB  - OBJECTIVE: To determine the association between acculturation, immigration, and
      prevalence of depression in older Mexican Americans. DESIGN: Cross-sectional
      analysis from a cohort study. SETTING: Urban and rural counties of the Central
      Valley of Northern California. PARTICIPANTS: One thousand seven hundred and
      eighty-nine Latinos recruited from a population-based sample (85% Mexican
      Americans) with a mean age of 70.6 (range 60-100; standard deviation (SD) =
      7.13); 58.2% were women. MEASUREMENTS: Depressive symptoms were assessed with the
      Center for Epidemiologic Studies--Depression scale (CES-D). Acculturation was
      measured with the Acculturation Rating Scale for Mexican Americans--II.
      Psychosocial, behavioral, and medical histories were also obtained. RESULTS: The
      prevalence of depression (CES-D > or = 16) was 25.4%. Women were at greater risk
      (32.0%) than men (16.3%; male/female odds ratio (OR) = 2.43, 95% confidence
      interval (CI) = 1.90-3.09). The prevalence of depression was higher among
      immigrants (30.4%, OR = 1.70, 95% CI = 1.36-2.13), bicultural participants
      (24.2%, OR = 1.66, 95% CI = 1.24-2.24), and less-acculturated participants
      (36.1%, OR = 2.95, 95% CI = 2.22-3.93) compared with U.S.-born (20.5%) and more
      acculturated groups (16.1%). When adjustments for education, income,
      psychosocial, behavioral, and health-problem factors were made, the least
      acculturated participants were at significantly higher risk of depression than
      highly acculturated Mexican Americans (OR = 1.56, 95% CI = 1.06-2.31).
      CONCLUSIONS: These findings are consistent with previously reported estimates of
      a higher prevalence of depression for older Mexican Americans than non-Hispanic
      Caucasians and African Americans and are the first to report the prevalence and
      risk of depression for older U.S.-born and immigrant Mexican Americans. The high
      prevalence of depression of the least acculturated group may be related to
      cultural barriers encountered by immigrants and less-acculturated older Mexican
      Americans and to poorer health status.

PMID- 11527488
TI  - Functional ability and oral health among older people: a longitudinal study from
      age 75 to 80.
AB  - OBJECTIVE: To examine whether functional ability at age 75 and age 80 is
      associated with oral health and use of dental services cross-sectionally and
      whether changes in functional ability from age 75 to age 80 are associated with
      oral health and regular use of dental services at age 80. DESIGN: The study
      included a random sample of 75-year-olds at baseline and a follow-up study 5
      years later. The data are treated as two cross-sectional studies at age 75 and
      80, respectively, and as a longitudinal study from age 75 to 80. SETTING: The
      western part of Copenhagen County. PARTICIPANTS: The two cross-sectional studies
      of 75- and 80-year-old people included 411 and 321 persons, respectively. The
      longitudinal study from age 75 to 80 included the 326 persons who participated in
      both surveys. MEASUREMENTS: Oral health status was measured roughly by number of
      teeth and chewing ability. Use of dental services was measured by frequency of
      visits to a dentist or denturist. Functional ability was measured by two scales
      on mobility in relation to tiredness and need of help. Changes in mobility from
      age 75 to 80 is described as (1) improved or sustained good, (2) decreased, and
      (3) sustained poor. Gender, chronic diseases, self-rated health, socio
      demographic factors, living alone, and social relations were included as possible
      confounders. RESULTS: The odds ratio of having no or few teeth was 1.7 (1.1-2.6)
      in 75-year-old individuals who felt tired in mobility, 1.7 (1.0-2.9) in 80-year
      old persons who needed help with mobility, and 2.7 (0.94-7.5) in persons with
      sustained need of help with mobility from age 75 to 80. The odds ratio of chewing
      difficulties was 1.7 (1.1-2.8) in 80-year-old people in need of help, and 1.8
      (1.1-3.0) in persons age 75 to 80 needing sustained help. Dentate 80-year-old
      persons who felt tired in mobility had an odds ratio of 2.0 (0.94-4.2) of not
      using dental services. CONCLUSIONS: The results indicate that oral impairment
      (e.g., having no or few teeth), oral functional limitations (e.g., chewing
      problems), and general functional limitations (e.g., mobility problems) are
      interrelated and that prevention of disabilities should be aimed at both
      functional limitations and oral health problems if the intention is to promote a
      good life in old age. In addition, the results point to the importance of taking
      problems in mobility seriously in delivering preventive services to old people
      because people who are tired or dependent on help seem to be at a higher risk of
      not using dental services regularly.

PMID- 11527489
TI  - Physician confidence and interest in learning more about common geriatric topics:
      a needs assessment.
AB  - OBJECTIVE: To assess physicians' confidence in and interest in learning more
      about 18 specific geriatric topics. DESIGN: Written survey. SETTING: Annual
      meetings of the American College of Physicians (ACP) and the American Academy of
      Family Physicians (AAFP). PARTICIPANTS: Seven hundred and fifty-eight physicians
      (547 ACP members, 211 AAFP members). MEASUREMENTS: For each topic, participants
      rated their confidence in performance, their peers' need for education, and their
      interest in learning more, using a five-point Likert scale. RESULTS: Survey
      participants were on average 16 years out of medical school and 61% were in a
      community primary care practice that included many geriatric patients on a
      primarily fee-for-service basis. High levels of interest in learning more about
      dementia, functional assessment, urinary incontinence, and sensory impairment
      were found. A substantial correlation (r =.44, P <.0001) between the proportion
      of seniors reported in the physicians' practice and confidence in performance in
      the areas surveyed was identified. CONCLUSIONS: These findings provide useful
      information on the physician-learner's perception of needs, which is important in
      the design of effective continuing education efforts in geriatrics.

PMID- 11527490
TI  - High body mass index does not predict mortality in older people: analysis of the
      Longitudinal Study of Aging.
AB  - OBJECTIVE: To determine the excess mortality associated with obesity (defined by
      body mass index (BMI)) in older people, with and without adjustment for other
      risk factors associated with mortality and for demographic factors. DESIGN:
      Retrospective cohort analysis of the Longitudinal Study of Aging (LSOA). SETTING:
      Nationally representative sample of community-dwelling older people.
      PARTICIPANTS: Seven thousand five hundred and twenty-seven participants age 70
      and older in 1984. MEASUREMENTS: We used Cox regression to calculate proportional
      hazards ratios for mortality over 96 months. We tested the hypothesis that
      increased BMI (top 15%) increased mortality rates in older people. RESULTS: Death
      occurred in 38% of the cohort: 54% of the thin (lowest 10% of the population, BMI
      <19.4 kg/m(2)), 33% of the obese (highest 15%, BMI> 28.5 kg/m(2)), and 37% of the
      remaining participants (normal) died. Adjustment for demographic factors, health
      services utilization, and functional status still demonstrated reduced mortality
      in obese older people (hazard ratio 0.86, 95% confidence interval (CI) = 0.77
      0.97) compared with normal. After adjustment, thin older people remained more
      likely to die (hazard ratio 1.46, 95% CI = 1.30-1.64) than normal older people.
      Sensitivity analyses for income, mortality during the first two years of follow
      up, and medical comorbidities did not substantively alter the conclusions.
      CONCLUSION: Obesity may be protective compared with thinness or normal weight in
      older community-dwelling Americans.

PMID- 11527491
TI  - On the use of surrogate respondents for controls in a case-control study of
      Alzheimer's disease.
AB  - OBJECTIVE: To examine the presence and extent of bias introduced by using
      surrogate respondents for healthy controls in a case-control study of Alzheimer's
      disease (AD). DESIGN: Comparative study of matched responses to questionnaire
      ascertaining lifestyle issues. SETTING: University Hospitals/Case Western Reserve
      University Alzheimer Center. PARTICIPANTS: Controls (n = 50) were identified
      through the Research Registry. Surrogates (n = 50) were their healthy relatives
      or friends. MEASUREMENTS: Answers in the areas of demographic and occupational
      history, smoking habits, medical history, dietary intake, and leisure and work
      activities were recorded. The analysis was based on methods for paired data.
      Continuous variables were analyzed, focusing on paired differences between self
      and surrogate responses. RESULTS: For occupations and exposures, over 80% of the
      surrogates agreed with the subjects on over 80% of the questions. On smoking
      history, over 90% of the surrogates agreed with the subjects on over 70% of the
      questions. On leisure and work activities, over 70% of the surrogates agreed with
      the subjects on over 50% of the questions. There was less agreement regarding
      medical history. For continuous variables, most paired t-tests of zero mean
      difference between self and surrogate responses resulted in nonrejection of this
      hypothesis. Computed mean differences were not always positive or always
      negative. CONCLUSION: We did not find systematic under- or overreporting by the
      surrogates of the controls. Therefore, if there are biases in the responses of
      surrogates of the AD cases in our case-control study, they would not be canceled
      out by using surrogates for the controls.

PMID- 11527493
TI  - Role of the clinical breast examination in breast cancer screening does this
      patient have breast cancer? Does this patient have breast cancer? Barton MB,
      Harris R, Fletcher SW JAMA 1999;282:1270-1280.

PMID- 11527492
TI  - Neuropsychological and genetic differences between age-associated memory
      impairment and mild cognitive impairment entities.
AB  - OBJECTIVE: To neuropsychologically and genetically compare age-associated memory
      impairment (AAMI) and mild cognitive impairment (MCI) entities and to determine
      what proportion of AAMI diagnosed individuals could also receive a MCI diagnosis.
      To compare the distribution of a previously known genetic risk factor for
      Alzheimer's disease (apolipoprotein E common polymorphism) associated with these
      two conditions with a sample of the normal aging. DESIGN: Neuropsychological and
      genetic assessments in AAMI and MCI individuals. Genetic assessment in AAMI, MCI,
      and control subjects. SETTING: General health centers and geriatric homes from
      northeastern Spain (Catalunya). PARTICIPANTS: One hundred and four subjects
      presenting subjective memory complaints were selected and the AAMI and MCI
      criteria were applied. One hundred and twenty-four healthy Spanish subjects age
      50 and older were defined as controls. MEASUREMENTS: Memory, language, and
      frontal lobe functions were assessed using standard neuropsychological tests. The
      apolipoprotein E (apo E) polymorphism was obtained by using polymerase chain
      reaction (PCR) and HhaI restriction endonuclease. RESULTS: Sixty-seven percent of
      previously diagnosed AAMI individuals could also be identified as MCI subjects.
      These MCI cases differed from those only-AAMI individuals both in
      neuropsychological and genetic analyses, performing worse not only on memory but
      also on language and frontal lobe tests and presenting high and low prevalences
      of the apo E epsilon 3/epsilon 4 and epsilon 3/epsilon 3 genotypes, respectively.
      The general AAMI sample of 93 individuals also differed from controls in the apo
      E genotype and allele distributions but these differences were no longer present
      after subtracting the MCI cases (63 subjects). These findings reflect that the
      differences between the memory impaired sample and the control sample regarding
      the apo E polymorphism were mainly attributable to MCI individuals and not to
      those who received only a diagnosis of AAMI alone. CONCLUSIONS: Our findings
      suggest that among AAMI subjects, those who also fulfill the MCI criteria present
      a neuropsychological and genetic profile closer to that previously related to
      Alzheimer's disease than those individuals only eligible for a diagnosis of AAMI.
      However, our findings also suggest that using only the AAMI criteria still
      appears to select a population that differs genetically from the normal older
      population.

PMID- 11527495
TI  - Ethnogeriatrics comes of age!

PMID- 11527496
TI  - Pressure ulcers: using what we know to improve quality of care.

PMID- 11527497
TI  - The shifting impact of UI.

PMID- 11527498
TI  - Functional ability and oral health: reintegrating mouth and body.

PMID- 11527499
TI  - Vascular and blood pressure effects of folic acid in older patients with
      cardiovascular disease.

PMID- 11527500
TI  - Breast cancer in older women.

PMID- 11527501
TI  - The cumulative effects of social class on mental status decline.

PMID- 11527502
TI  - Survival in Finnish centenarians in relation to apolipoprotein E polymorphism.

PMID- 11527503
TI  - Treatment-resistant atopic dermatitis.

PMID- 11527504
TI  - Functional status and mortality in community-dwelling older people.

PMID- 11527505
TI  - Phenotyping of Campylobacter jejuni and Campylobacter coli by a quantitative
      antibiogram [MIC] typing scheme using Euclidean distances [QATED].
AB  - BACKGROUND: Enteropathogenic Campylobacter jejuni and C. coli are presently the
      most common cause of acute bacterial gastroenteritis in the developed world. An
      understanding of sources and means of transmission of Campylobacter is an
      essential factor in order to reduce the incidence of Campylobacter-related
      gastroenteritis in man. Consequently a reproducible, sensitive and well
      standardised typing scheme is critical in the successful discrimination of
      strains and in the subsequent investigations of outbreaks. For this purpose, a
      phenotypic typing scheme based on quantitative antibiogram determination based on
      Euclidean distance (QATED), was developed. RESULTS AND CONCLUSION: The results
      obtained with this typing scheme demonstrated that individual livers of colonized
      pigs could be infected with multiple strains of Campylobacter spp. and subspecies
      types. In conclusion, phenotyping of Campylobacter jejuni and C. coli by QATED is
      a simple, inexpensive and discriminatory sub-species characterisation scheme,
      which may be useful in primary diagnostic clinical laboratories, where no
      specialist Campylobacter phenotyping or molecular genotyping schemes exist. It is
      especially suitable for food-borne outbreak investigations in the community,
      where a rapid and local response is required to aid with public health
      epidemiological investigations.

PMID- 11527506
TI  - Joint effects of citrus peel use and black tea intake on the risk of squamous
      cell carcinoma of the skin.
AB  - BACKGROUND: Differences in tea drinking habits and/or citrus peel use are likely
      to vary by populations and could contribute to the inconsistencies found between
      studies comparing their consumption and cancer risk. METHODS: A population-based
      case-control study was used to evaluate the relationships between citrus peel use
      and black tea intake and squamous cell carcinoma (SCC) of the skin. Moreover, we
      assessed the independent and interactive effects of citrus peel and black tea in
      the development of SCC. RESULTS: Hot and iced teas were consumed by 30.7% and
      51.8% of the subjects, respectively. Peel consumption was reported by 34.5% of
      subjects. Controls were more likely than were cases to report citrus peel use
      (odds ratio (OR) = 0.67) and hot tea intake (OR = 0.79). After adjustment for hot
      and iced tea intake, the ORs associated with citrus peel use were 0.55 and 0.69,
      respectively, whereas the corresponding adjusted ORs for hot and iced tea intake
      after adjustment for citrus peel use were 0.87 and 1.22 respectively. Compared
      with those who did not consume hot black tea or citrus peel, the adjusted ORs
      associated with sole consumption of hot black tea or citrus peel were 0.60 and
      0.30, respectively. Subjects who reported consumption of both hot black tea and
      citrus peel had a significant marked decrease (OR= 0.22; 95% CI = 0.10 - 0.51)
      risk of skin SCC. CONCLUSION: These results indicate that both citrus peel use
      and strong (hot) black tea have independent potential protective effects in
      relation to skin SCC.

PMID- 11527507
TI  - Effects of microcosm scaling and food resources on growth and survival of larval
      Culex pipiens.
AB  - BACKGROUND: We used a simple experimental design to test for the effects of
      microcosm scaling on the growth and survival of the mosquito, Culex pipiens.
      Microcosm and mesocosm studies are commonly used in ecology, and there is often
      an assumption that scaling doesn't affect experimental outcomes. The assumption
      is implicit in the design; choice of mesocosms may be arbitrary or based on
      convenience or cost. We tested the hypothesis that scale would influence larvae
      due to depth and surface area effects. Larvae were predicted to perform poorly in
      microcosms that were both deep and had small openings, due to buildup of waste
      products, less exchange with the environment, and increased competition. To
      determine if the choice of scale affected responses to other factors, we
      independently varied leaf litter quantity, whose effects on mosquitoes are well
      known. RESULTS: We found adverse effects of both a lower wall surface area and
      lower horizontal surface area, but microcosm scale interacted with resources such
      that C. pipiens is affected by habitat size only when food resources are scarce.
      At low resource levels mosquitoes were fewer, but larger, in microcosms with
      smaller horizontal surface area and greater depth than in microcosms with greater
      horizontal surface area and shallower depth. Microcosms with more vertical
      surface area/volume often produced larger mosquitoes; more food may have been
      available since mosquitoes browse on walls and other substrates for food.
      CONCLUSIONS: The interaction between habitat size and food abundance is
      consequential to aquatic animals, and choice of scale in experiments may affect
      results. Varying surface area and depth causes the scale effect, with small
      horizontal surface area and large depth decreasing matter exchange with the
      surrounding environment. In addition, fewer resources leads to less leaf surface
      area, and the effects of varying surface area will be greater under conditions of
      limiting resources. This leads to smaller size, which limits fecundity and
      survival. Choice of container size, either by ovipositing females or researchers,
      interacts with a major aspect of the ecology of animals; obtaining resources in a
      resource-limited environment.

PMID- 11527508
TI  - Systematic reviews of complementary therapies - an annotated bibliography. Part
      3: homeopathy.
AB  - BACKGROUND: Complementary therapies are widespread but controversial. We aim to
      provide a comprehensive collection and a summary of systematic reviews of
      clinical trials in three major complementary therapies (acupuncture, herbal
      medicine, homeopathy). This article is dealing with homeopathy. Potentially
      relevant reviews were searched through the register of the Cochrane Complementary
      Medicine Field, the Cochrane Library, Medline, and bibliographies of articles and
      books. To be included articles had to review prospective clinical trials of
      homeopathy; had to describe review methods explicitly; had to be published; and
      had to focus on treatment effects. Information on conditions, interventions,
      methods, results and conclusions was extracted using a pretested form and
      summarized descriptively. RESULTS: Eighteen out of 22 potentially relevant
      reviews preselected in the screening process met the inclusion criteria. Six
      reviews addressed the question whether homeopathy is effective across conditions
      and interventions. The majority of available trials seem to report positive
      results but the evidence is not convincing. For isopathic nosodes for allergic
      conditions, oscillococcinum for influenza-like syndromes and galphimia for
      pollinosis the evidence is promising while in other areas reviewed the results
      are equivocal. INTERPRETATION: Reviews on homeopathy often address general
      questions. While the evidence is promising for some topics the findings of the
      available reviews are unlikely to end the controversy on this therapy.

PMID- 11527509
TI  - Obesity and weight change related to parity and breast-feeding among parous women
      in Brazil.
AB  - OBJECTIVE: Studies on the independent role of parity in long-term body weight
      change in economically developing countries are scarce and inconclusive, and only
      a few studies have taken into account patterns of breast-feeding. This
      association was examined in a national cross-sectional survey representative of
      Brazilian parous women. DESIGN AND SETTING: The survey conducted in 1996 measured
      women's height and weight in the household and data on weight prior to the first
      pregnancy, parity and breast-feeding were recalled. SUBJECTS: A sample of 2338
      parous women, 15 to 49 years of age, 29 months after last delivery on average,
      had current body mass index (BMI, in kg m(-2)) modelled through hierarchical
      multiple linear regression analysis. Explanatory variables included parity, days
      of predominant breast-feeding, BMI pre-pregnancy, socio-economic, geographic,
      demographic and other reproductive variables. RESULTS: Prevalences of overweight
      (BMI = 25.0-29.9 kg m(-2)) and obesity (BMI > or = 30.0 kg m(-2)) were 25.2% and
      9.3%. The overall mean weight gain per year after the first pregnancy was 0.90 kg
      for an average time since first pregnancy of eight years. BMI pre-pregnancy
      modified the association between current BMI and parity. Therefore, weight change
      attributed to parity calculated for a woman of average height (1.56 m) was 0.60
      kg greater for primiparous women with a BMI pre-pregnancy of 30 kg m(-2),
      compared with women with BMI pre-pregnancy of 25 kg m(-2). This greater weight
      retention among obese women was 1.21 kg for women with two children and 1.82 kg
      for women with three or more children. Parity reduced the effect of weight loss
      associated with lactation (1.75 kg for six months of lactation among primiparous
      women and 0.87 kg among women with three or more children). For the sub-sample of
      793 primiparous women, a weight decrease of 300 g was associated with each month
      of predominant breast-feeding for all prior BMI levels. CONCLUSIONS: In this
      study, weight change associated to reproduction was highly dependent on BMI
      previous to pregnancy and the effects of parity and lactation were small.

PMID- 11527510
TI  - Ecological variation of intake of cassava food and dietary cyanide load in
      Nigerian communities.
AB  - AIM: To study the ecological variation of intake of cassava foods and dietary
      cyanide load. DESIGN: Ecological study design. SETTING: Five communities in south
      western Nigeria where tropical ataxic neuropathy (TAN) was described as endemic
      (area A), 11 communities in south-western Nigeria where TAN was described as
      absent (area B), and five communities in northern Nigeria (area C). SUBJECTS:
      Subjects were randomly sampled from selected communities. Intake of cassava foods
      was estimated from dietary history and dietary cyanide load was estimated from
      urine thiocyanate concentrations. Residual cyanogens in cassava food samples from
      the community markets were determined. RESULTS: In total, 1272 subjects from 21
      communities - 238 from area A, 659 from area B and 375 from area C - were
      selected. Intake of cassava food per person per week was 17 meals in area A, 10
      meals in area B, and one meal in area C. Geometrical mean urine thiocyanate
      concentrations were 73 micromol l(-1), 51 micromol l(-1) and 17 micromol l(-1) in
      areas A, B and C, respectively. Mean residual cyanogen content in cassava food
      samples was 16 mg HCN eq kg(-1) (confidence interval (CI) 13-18) in area A, and
      13 mg HCN eq kg(-1) in area B (CI 11-14). CONCLUSION: This study shows that the
      intake of cassava foods and dietary cyanide load is high in several communities
      in south-western Nigeria, predominantly in communities where TAN has been
      reported. Dietary cyanide load in these communities appears to be determined by
      the combination of frequency of intake and cyanogen content of cassava foods.
      Measures to improve the effectiveness of removal of cyanogen from cassava roots
      during processing are needed in the affected communities.

PMID- 11527511
TI  - Cattle eradication and malnutrition in under five's: a natural experiment in
      Botswana.
AB  - BACKGROUND: An outbreak of contagious bovine pleuropneumonia (CBPP) in the
      northern part of Botswana in 1996 was contained through eradication of all heads
      of cattle in Ngamiland district (Ngami East and West) in the period April 1996 to
      February 1997. This disaster posed a serious threat to those who depended on the
      livestock sector for sustenance and to the nutrition security of the population,
      especially the under five's. AIM: The aim of this study was to assess the impact
      of the cattle eradication on the nutritional status of children. METHOD: A
      secondary analysis of existing data from the Botswana National Nutrition
      Surveillance System enabled us to study the impact of this disaster on
      malnutrition in the under five's by comparing quarterly malnutrition rates for
      Ngami East with national figures for the period of January 1995 to March 1998.
      RESULTS: While the risk for malnutrition among under five's in Ngami East
      increased from 0.046 to 0.105 during the study period, giving a relative risk of
      2.299, the increase in risk for Botswana was from 0.133 to 0.139, giving a
      relative risk of 1.048. The attributable risk for cattle eradication impact on
      malnutrition was 4.6% for Botswana and 54.4% for Ngami East. CONCLUSION: The
      cattle eradication impacted seriously on the food and nutrition security of the
      under five's in Ngami East, compared with the country as a whole.

PMID- 11527512
TI  - Maternal consumption of pulque, a traditional central Mexican alcoholic beverage:
      relationships to infant growth and development.
AB  - OBJECTIVES: To document the consumption during pregnancy of pulque, a traditional
      central Mexican alcoholic beverage, and its relationship to subsequent infant
      size, physical growth and performance on the Bayley Scales of Infant Development.
      DESIGN: Prospective cohort study. SETTING: Six villages in rural, central Mexico
      in 1984-1985. SUBJECTS: Seventy mother-infant pairs. RESULTS: Most women (72.9%)
      consumed pulque during pregnancy, and 28.6% consumed more than 150 g ethanol
      week(-1) from the beverage. Individuals who consumed pulque showed no
      compensating decrease in energy obtained from other foods. Pulque consumption
      possessed curvilinear relationships with both infant length (at 1 and 6 months)
      and Bayley mental performance (at 6 months). Heavy pulque intakes were associated
      with smaller infant size and poorer mental performance. In modest quantities,
      pulque consumption may have been beneficial due to its micronutrient content.
      CONCLUSIONS: Intakes of alcohol from pulque were common among pregnant women in
      these rural, central Mexican villages. Given current scientific knowledge of the
      adverse effects of ethanol on foetal development, public health interventions are
      needed to reduce heavy pulque consumption during pregnancy in some areas of rural
      Mexico.

PMID- 11527513
TI  - The potential contribution of increased vegetable and fruit consumption to health
      gain in the European Union.
AB  - BACKGROUND: The risk of many important diseases can be reduced by consuming a
      diet rich in vegetables and fruit. For this reason the World Health Organization
      (WHO) recommends a daily intake of more than 400 g person(-1). The pattern of
      both the supply and intake of vegetables and fruit and the potential health gain
      achieved by increasing intake in the European Union (EU) and three accession
      countries are presented in this paper. METHODS: Patterns of supply and dietary
      intake were assessed using (1) FAO food balance sheets, which allow comparison
      between the levels of supply in countries but do not reflect actual intake; and
      (2) survey data reflecting dietary intake. Using WHO mortality data for coronary
      heart and cerebrovascular disease and major cancers up to age 65 years, the
      number of preventable deaths is estimated, assuming vegetable and fruit
      consumption were levelled up to that of the highest consuming group, and assuming
      relative risks of 0.5, 0.7 or 0.9. RESULTS: Vegetable and fruit consumption
      varies considerably between EU Member States. The populations of about half
      (seven) of the EU Member States have a mean daily intake of less than 275 g.
      Using the best current estimates of relative risk, over 26,000 deaths before the
      age of 65 years would be prevented annually in the EU if intake was levelled up
      to the highest consumption levels (and about double this number of deaths before
      the age of 75 years). CONCLUSION: Increasing the intake of vegetables and fruit
      is feasible and could result in considerable improvements in public health within
      the EU. Priority should be given to developing methods that demonstrate the
      burden of disease caused by too low intakes of vegetables and fruit. This would
      enable the appropriate social, cultural and economic policies to be developed
      within the EU.

PMID- 11527514
TI  - Is principal components analysis necessary to characterise dietary behaviour in
      studies of diet and disease?
AB  - OBJECTIVE: To assess the relative ability of principal components analysis (PCA)
      derived dietary patterns to correctly identify cases and controls compared with
      other methods of characterising food intake. SUBJECTS: Participants in this study
      were 232 endometrial cancer cases and 639 controls from the Western New York Diet
      Study, 1986-1991, frequency-matched to cases on age and county of residence.
      DESIGN: Usual intake in the year preceding interview of 190 foods and beverages
      was collected during a personal interview using a detailed food-frequency
      questionnaire. Principal components analysis identified two major dietary
      patterns which we labelled 'healthy' and 'high fat'. Classification on disease
      status was assessed with separate discriminant analyses (DAs) for four different
      characterisation schemes: stepwise DA of 168 food items to identify the subset of
      foods that best discriminated between cases and controls; foods associated with
      each PCA-derived dietary pattern; fruits and vegetables (47 items); and stepwise
      DA of USDA-defined food groups (fresh fruit, canned/frozen fruit, raw vegetables,
      cooked vegetables, red meat, poultry, fish and seafood, processed meats, snacks
      and sweets, grain products, dairy, and fats). RESULTS: In general, classification
      of disease status was somewhat better among cases (54.7% to 67.7%) than controls
      (54.0% to 63.1%). Correct classification was highest for fruits and vegetables
      (67.7% and 62.9%, respectively) but comparable to that of the other schemes
      (49.5% to 66.8%). CONCLUSIONS: Our results suggest that the use of principal
      components analysis to characterise dietary behaviour may not provide substantial
      advantages over more commonly used, less sophisticated methods of characterising
      diet.

PMID- 11527515
TI  - Maternal knowledge, attitude and practice regarding folic acid intake during the
      periconceptional period.
AB  - OBJECTIVE: To study the knowledge, attitude and practice of pregnant women
      regarding periconceptional folic acid (FA) intake. DESIGN: Questionnaire-based
      prospective study. SETTING: Antenatal clinic of a District General Hospital.
      SUBJECTS: Three-hundred pregnant women in an antenatal clinic. RESULTS: Nearly
      all (298/300) had heard of FA. A majority (275/300, 91%) knew that FA could
      prevent neural tube defects, and married women those with higher education those
      of Social Classes 1-3 and women over 30 years of age were more likely to be thus
      aware. Knowledge about the correct timing of FA intake was seen in 76% and was
      more likely in those with higher education married women and women age over 30
      years Intake of FA in the periconceptional period was seen in 134/300 (44.6%)
      women and was most likely in the married, Social Classes 1-3, women with higher
      education (all P<0.001), non-smokers women with a planned pregnancy and women
      aged 30 years and over CONCLUSIONS: The knowledge of the correct timing of FA
      intake was present in only 76%. Less than half (44.6%) had taken FA in the
      periconceptional period, and this was far more common in the more 'privileged'
      classes. Low socio-economic status, age less than 30 years, lower educational
      status and unplanned pregnancy were high risk factors for not taking FA. The
      challenge to the medical profession for targeting this group cannot be over
      emphasised.

PMID- 11527516
TI  - Is the link between nutrients and foods understood? The case of fibre and folate.
AB  - OBJECTIVES: To assess and contrast awareness of the link between dietary fibre
      and folate and their major food sources (fruit, vegetables, bread and cereals).
      DESIGN: Mailed questionnaire investigating changes made to dietary intake of
      fibre, folate, fruit, vegetables, bread and cereals in the previous six months.
      SETTING: The survey was conducted between June and November 1998 in the
      Australian Capital Territory. SUBJECTS: One thousand one hundred and twenty-six
      adults randomly selected from the electoral roll. RESULTS: More women than men in
      both older (50+ years) and younger (18-49 years) age groups reported increasing
      their consumption of folate, fibre, fruit and vegetables in the prior six months.
      In contrast, more men than women reported increased consumption of bread,
      cereals, rice and pasta in the previous six months. For food categories and
      fibre, less than 4% of respondents were unsure about changes in these food
      habits. However, 26% of men and women were 'not sure' about changes to folate
      intake. Similar proportions of men and women (about 33%) reported consuming more
      fruit, vegetables or cereal-based foods over the prior six months, yet only 6% of
      these men and 14% of these women reported consuming more folate. In contrast, 44%
      of men and 51% of women who reported consuming more plant foods also reported
      consuming more dietary fibre. CONCLUSIONS: The results suggested that subjects,
      particularly the younger age group, had a poor understanding of the relationship
      between folate intake and its major food sources. The understanding of the
      relationship between fibre intake and its food sources appeared substantial, but
      confusion about specific food sources was still evident. These outcomes question
      the effectiveness of nutrition education used to date, particularly for the
      current priority of increasing folate intake in younger women in the new, 'health
      claims' environment.

PMID- 11527517
TI  - Underreporting of energy intake in repeated 24-hour recalls related to gender,
      age, weight status, day of interview, educational level, reported food intake,
      smoking habits and area of living.
AB  - OBJECTIVE: The aims of the present study were (1) to evaluate the degree to which
      underreporting of energy intake by repeated 24-hour recalls was related to
      gender, age, weight status, day of interview, educational level, smoking habits
      and area of living, and (2) to compare the dietary characteristics of
      underreporters with those of others. DESIGN: Cross-sectional study. Ten 24-hour
      recalls were performed during a one-year period. SETTING: The Vasterbotten
      intervention programme of cardiovascular disease and diabetes in Northern Sweden.
      SUBJECTS: Ninety-four men and 99 women in four age groups: 30, 40, 50 and 60
      years. RESULTS: The prevalence of men and women with a food intake level (FIL;
      reported energy intake divided by estimated basal metabolic rate) below 1.2 was
      44% and 47%, respectively. The youngest age group had higher FIL values than the
      oldest age group for both men (1.5 versus 1.1) and women (1.4 versus 1.1). The
      prevalence and magnitude of underreporting were directly related to body mass
      index (BMI; correlation coefficient: -0.47 (men) and -0.55 (women)). Smokers had
      a lower FIL value (1.1) than non-smokers (1.3). The nutrient density was lower
      for the group with high FIL values for protein and calcium and higher for fat and
      sucrose. The upper FIL group often had higher intake frequencies and larger
      portion sizes than the lower FIL group. CONCLUSIONS: Underreporting of energy
      intake is prevalent when 24-hour recalls are used, but the prevalence differs
      between sub-groups in the population. BMI was the main predictor of
      underreporting but also old age and smoking seem to contribute in this aspect.
      Socially desirable food items were not underreported to the same extent as
      socially undesirable food items. The intake frequencies and portion sizes partly
      explained the differences in FIL.

PMID- 11527518
TI  - Breast-feeding in sub-Saharan Africa: outlook for 2000.

PMID- 11527519
TI  - Tetralogy of Fallot.
AB  - The optimal surgical approach and timing for patients with tetralogy of Fallot
      remain controversial. There are two options in current practice: a two-stage
      repair (an initial palliative aortopulmonary shunt at an early age followed by
      complete repair at an older age) or primary complete repair. There has been a
      trend towards primary repair at a young age, which can be attributed to advances
      in anesthetic and cardiac surgical techniques. Primary repair has several
      advantages. The correction can be done in one operation and shunt complications
      are avoided. Progressive right ventricular fibrosis, ventricular hypertrophy, and
      chronic hypoxia are avoided, which may reduce the incidence of late ventricular
      arrhythmias. However, surgical correction at a young age is associated with an
      increased incidence of transannular patching and consequent pulmonary
      regurgitation. Progressive pulmonary regurgitation is associated with late
      ventricular arrhythmias and sudden death. These consequences may be prevented by
      timely pulmonary valve replacement. Palliative procedures include an
      aortopulmonary shunt, balloon dilation of the right ventricular tract, and stent
      placement. Of these measures, the aortopulmonary shunt is preferred, as it
      results in a more predictable outcome. Complications associated with shunt
      placement include shunt occlusion, pulmonary artery distortion, and occasionally,
      volume overloading of the left ventricle and pulmonary circulation. Institutional
      and surgeon preferences exist for either surgical strategy, and ultimately are
      justifiable when they produce the best outcomes for the individual patient. The
      optimal surgical strategy has to be determined by large prospective randomized
      studies that compare the functional status of the pulmonary valve and the need
      for reoperation at long-term follow-up.

PMID- 11527521
TI  - Postoperative Cardiac Arrhythmias in Children.
AB  - The cardiac rhythm can be very labile in the early postoperative period,
      necessitating a high degree of vigilance. Bradycardia may be due to sinus node
      dysfunction or varying degrees of atrioventricular block, both of which are
      usually due to surgical trauma. Temporary pacing, using implanted temporary
      pacing wires, should be readily available. Most often, bradycardias are
      transient. Patients who fail to recover an adequate sinus rhythm or
      atrioventricular conduction within 7 to 10 days should be treated with a
      pacemaker. Supraventricular tachycardia, ventricular tachycardia, and junctional
      ectopic tachycardia are the major tachyarrhythmias of the early postoperative
      period. Establishing the diagnosis may require electrocardiography, atrial
      electrocardiograph recordings, and the use of intravenous adenosine. The
      management options for patients with tachyarrhythmias include vagal maneuvers,
      hypothermia, pacing, drug therapy, catheter ablation, direct-current
      cardioversion, and adjuvant measures. Electrolytes and acid-based balance should
      be checked in all patients with an arrhythmia and optimized if necessary.

PMID- 11527520
TI  - Pediatric Primary Pulmonary Hypertension.
AB  - Primary pulmonary hypertension is a disease for which there is no single best
      therapy. Rather, it is a process that progresses inexorably to disability and
      death, for which there are a variety of palliative therapies, all with
      significant side effects, and none curative. Nevertheless, it is clear that the
      available therapies improve the quality of life and prolong life; failure to
      offer therapy for patients with this disease in the current era is indefensible.
      As primary pulmonary hypertension progresses, one must chose from among the
      available therapies the regimen that provides the most benefit for the patient
      with the least associated morbidity. Organ replacement is appropriate only after
      all other available therapies have been exhausted. The recommended hierarchy of
      therapy is 1) anticongestive therapy, anticoagulation, and supplemental oxygen,
      2) calcium channel blockade, 3) continuous intravenous prostacyclin, 4) beta
      receptor agonists for cardiac support, and 5) lung transplantation. Newer
      therapies, described in this review, soon will be incorporated into this
      hierarchy.

PMID- 11527522
TI  - Congenital Coronary Artery Abnormalities in Children.
AB  - After a significant coronary artery abnormality is recognized in a pediatric
      patient, surgery or appropriate transcatheter intervention should be performed.
      The risk of fatality from a congenital coronary abnormality far outweighs the
      small risks of surgical or transcatheter intervention. Angiography, although
      considered the state-of-the-art method of diagnosis, has significant spatial
      limitations and is not always diagnostic of aberrant coronary origins from the
      contralateral aortic sinus. In the hands of an experienced coronary imager, color
      flow Doppler echocardiography is one of the best diagnostic tools for congenital
      coronary abnormalities. Symptoms of a coronary abnormality vary from none to a
      sudden coronary event that may result in death. Awareness of subtle as well as
      obvious symptoms is essential for a timely intervention. Surgical or
      transcatheter intervention in an asymptomatic child with a coronary abnormality
      is controversial, but it is becoming more acceptable due to a better
      understanding of the risks involved in unrepaired congenital coronary
      abnormalities. Surgical reimplantation is the treatment of choice for a patients
      with a pulmonary origin of a coronary artery. Surgical unroofing of the
      intramural segment is preferable in an aberrant coronary origin from the
      contralateral aortic sinus. Surgical enlargement of a stenotic ostium is
      recommended for ostial stenosis. Transcatheter coil embolization is becoming the
      treatment of choice of large coronary artery fistula.

PMID- 11527523
TI  - Cerebral Sinovenous Thrombosis.
AB  - Cranial sinovenous disorders comprise a disparate group of illnesses affecting
      one or more intracranial venous sinuses and cerebral veins, alone or in
      combination, due to a variety of causes. As medical knowledge advances, fewer and
      fewer patients have an "idiopathic" diagnosis, with causes clarified in an ever
      increasing number of patients. These not only include the long-known puerperal,
      marantic, infective, and traumatic causes, but in recent years, also a variety of
      congenital and acquired coagulation disorders, such as protein S, protein C, and
      antithrombin III deficiency. Certain sinuses are preferentially involved with
      certain causative entities; for example, cavernous and lateral sinuses are more
      frequently occluded in relation to infectious processes, either directly or as a
      parameningeal focus, whereas the superior sagittal sinus is most often occluded
      by trauma, tumor, or coagulopathy. The optimal treatment of sinovenous occlusion
      depends on establishing the cause with alacrity, because delays in diagnosis may
      lead to life-threatening hyperpyrexia, elevations in intracranial pressure,
      venous infarctions, seizures, coma, and death. However, because up to a third of
      patients with nonseptic occlusions may survive untreated, with few residua,
      controversy persists regarding optimal management. There has been a dearth of
      randomized, prospective treatment trials in this group of disorders. The little
      data that exist suggest that rapid control of infection, seizure prophylaxis, and
      anticoagulation must be achieved early so as to prevent progression of thrombosis
      and intracranial venous hypertension. In recent years, direct retrograde venous
      thrombolysis has become increasingly available, and has produced such remarkable
      results that it is likely soon to become the primary treatment of choice for the
      nontraumatic or nontumoral occlusions.

PMID- 11527524
TI  - Subarachnoid Hemorrhage.
AB  - Patients presenting with subarachnoid hemorrhage from aneurysmal rupture benefit
      from early repair of the aneurysm. Recent advances in endovascular technology now
      allow informed discussion of the merits of surgical versus endovascular repair of
      the aneurysm. Patients need close observation in an intensive-care unit following
      subarachnoid hemorrhage to diagnose and treat the multiple complications that
      result. These complications include hydrocephalus, fever, neurogenic pulmonary
      and cardiac dysfunction, and the development of delayed cerebral ischemia from
      vasospasm. There exist effective medical and endovascular treatments for cerebral
      vasospasm.

PMID- 11527525
TI  - Asymptomatic Internal Carotid Artery Origin Stenosis.
AB  - Proper therapy for patients with internal carotid artery stenosis requires a
      precise pathophysiologic diagnosis that includes characterization and
      localization of ischemic disease of the brain and knowledge of the arterial
      disease and the collateral cerebral circulation. Noninvasive techniques such as
      duplex ultrasound and transcranial Doppler, magnetic resonance angiography, and
      CT angiography allow precise determination of the stroke subtype and parent
      arterial pathology. Antiplatelet agents prevent the formation of thrombus on
      carotid artery atherosclerotic plaque. 3-Hydroxy-3-methyglutaryl coenzyme A
      reductase inhibitors may help stabilize carotid plaques by altering the plaque
      morphology and reducing inflammation. Carotid endarterectomy, which is the only
      procedure proven to be beneficial for patients with asymptomatic disease, should
      be considered primary intervention. Until ongoing trials for interventional
      procedures are completed, carotid artery angioplasty and stenting should be
      considered only in patients with contraindications to carotid endarterectomy. It
      can be argued that an ideal clinical trial in a high-risk population has not yet
      been completed. This factor has become even more important with the development
      of stenting procedures. We have long advocated a trial of only treating patients
      with hemodynamically significant stenotic lesions (70% to 99%).

PMID- 11527526
TI  - Synthesis of the alpha-D-GlcpA-(1-->3)-alpha-L-Rhap-(1-->2)-L-Rha trisaccharide
      isolated from the cell wall hydrolyzate of the green alga, Chlorella vulgaris.
AB  - The title trisaccharide was synthesized from 6-O-acetyl-2,3,4-tri-O-benzyl-alpha
      D-glucopyranosyl chloride (10), ethyl 2,4-di-O-benzyl-1-thio- (5) and benzyl 3,4
      di-O-benzyl-alpha-L-rhamnopyranoside (9). The disaccharide 11 obtained from
      compounds 5 and 10 was used as the glycosyl donor to glycosylate the
      rhamnopyranoside derivative 9 having free OH-2 using the NIS-AgOTf-mediated
      glycosylation methodology. Zemplen deacetylation of the trisaccharide 12 resulted
      in the 6"-OH derivative (13), which was selectively oxidized with CrO3 to the
      uronic acid derivative 14. The benzyl groups were removed by catalytic
      hydrogenolysis to furnish the target trisaccharide (1).

PMID- 11527527
TI  - Synthesis and characterisation of N-glycosyl amines from the reaction between 4,6
      O-benzylidene-D-glucopyranose and substituted aromatic amines and also between 2
      (o-aminophenyl)benzimidazole and pentoses or hexoses.
AB  - Twelve N-glycosyl amines were synthesised using 4,6-O-benzylidene-D-glucopyranose
      and different substituted aromatic amines, including some diamines that resulted
      in bis-glycosyl amines. Another set of six N-glycosyl amines was synthesised
      using different hexoses and pentoses and 2-(o-aminophenyl)benzimidazole. All
      compounds were isolated as solid products and purified, their elemental
      compositions were established, and these were characterised by NMR (1H and 13C),
      UV-Vis, and FTIR spectroscopy, by FAB mass spectrometry (molecular-ion peaks gave
      molecular weights), and by their optical rotations. While the protected
      saccharide, 4,6-O-benzylidene-D-glucopyranose, exists as a mixture of beta and
      alpha anomers in solution, the corresponding N-glycosyl amines were of only the
      beta anomeric form as determined by NMR and FTIR spectroscopy. On the other hand,
      N-glycosyl amines synthesised from 2-(o-aminophenyl)benzimidazole prefer the
      alpha anomeric form, and in two cases a mixture of both the beta and the alpha
      anomers were observed. The trends observed in the chemical shifts were compared
      among different products.

PMID- 11527528
TI  - Stereoselective synthesis of [13C]methyl 2-[15N]amino-2-deoxy-beta-D
      glucopyranoside derivatives.
AB  - Efficient syntheses of three [13C]methyl 2-[15N]amino-2-deoxy-beta-D
      glucopyranoside derivatives are described. Amination of the D-glucal with
      (saltmen)Mn(15N) proceeded with 11:1 stereoselectivity favoring the gluco
      configuration; subsequent methylation of the [15N]lactol using [13C]iodomethane
      and silver(I) oxide afforded the doubly labeled beta glucoside in high yield.
      This compound served as the common precursor for three [13C]methyl 2
      [15N]aminoglucosides: (2-[15N]trifluoroacetyl-), (2-[15N]acetyl-), and (2
      [15N]azido-). Selected heteronuclear coupling constants are reported.

PMID- 11527529
TI  - Synthesis of peracetylated chacotriose.
AB  - Steroidal glycoalkaloids of many Solanum species have recognized biological
      activities, especially those containing the glycosyl moiety alpha-L
      rhamnopyranosyl-(1-->2)-[alpha-L-rhamnopyranosyl-(1-->4)]-D-glucopyranose
      (chacotriose) whose peracetate is here synthesized and characterized by complete
      1H and 13C NMR assignment.

PMID- 11527530
TI  - Synthesis of a divalent glycoside of an alpha-galactosyl disaccharide epitope
      involved in the hyperacute rejection of xenotransplantation.
AB  - 3,6-dioxaoct-1,8-diyl di-(3-O-alpha-D-galactopyranosyl-beta-D-galactopyranoside)
      was synthesized for use in research on hyperacute rejection of
      xenotransplantation. The trichloroacetate method was successfully applied to form
      stereoselectively the alpha-D-galactosyl linkage under mild reaction conditions
      and a simple procedure. The divalent O-glycoside was formed from the
      corresponding trichloroacetimidate in one step with reasonable yield.

PMID- 11527531
TI  - Binding properties and esterase activity of monoclonal antibodies elicited
      against sucrose 6-heptylphosphonate.
AB  - Various sugar phosphonates were prepared by a Mitsunobu condensation between
      phosphonic diacids and properly protected carbohydrates. 6'-O-p
      Aminophenylsucrose 6-heptylphosphonate was coupled to Bovine Serum Albumin (BSA)
      and Keyhole Limpet Hemocyanin (KLH) and the KLH conjugate was used for generation
      of monoclonal antibodies. Binding properties of these antibodies were screened by
      competitive enzyme-linked immunosorbent assay (ELISA) using the BSA conjugate. A
      monoclonal antibody with good binding properties showed a regioselective esterase
      activity toward 6-octanoylsucrose compared with 6'-octanoylsucrose.

PMID- 11527532
TI  - Role of Phe286 in the recognition mechanism of cyclomaltooligosaccharides
      (cyclodextrins) by Thermoactinomyces vulgaris R-47 alpha-amylase 2 (TVAII). X-ray
      structures of the mutant TVAIIs, F286A and F286Y, and kinetic analyses of the
      Phe286-replaced mutant TVAIIs.
AB  - Phe286 located in the center of the active site of alpha-amylase 2 from
      Thermoactinomyces vulgaris R-47 (TVAII) plays an important role in the substrate
      recognition for cyclomaltooligosaccharides (cyclodextrins). The X-ray structures
      of mutant TVAIIs with the replacement of Phe286 by Ala (F286A) and Tyr (F286Y)
      were determined at 3.2 A resolution. Their structures have no significant
      differences from that of the wild-type enzyme. The kinetic analyses of Phe286
      replaced variants showed that the variants with non-aromatic residues, Ala
      (F286A) and Leu (F286L), have lower enzymatic activities than those with aromatic
      residues, Tyr (F286Y) and Trp (F286W), and the replacement of Phe286 affects
      enzymatic activities for CDs more than those for starch.

PMID- 11527533
TI  - Identification and structural analysis of synthetic oligosaccharides of Shigella
      sonnei using MALDI-TOF MS.
AB  - MALDI-TOF mass spectroscopy was used for the molecular weight determination of
      protected synthetic oligosaccharides related to a cell surface bacterial
      polysaccharide. By-products containing chlorinated protecting groups caused
      isotopic patterns characteristic of the natural isotopic distribution of
      chlorine, were identified on the basis of isotopic distribution. 2,4,6
      Trihydroxyacetophenone (THAP) as a matrix was better than 2,5-dihydroxybenzoic
      acid (DHB) for compounds containing chlorine, since monoisotopic resolution and
      no fragmentation were observed. In the post source decay (PSD) mode the
      identification of the oligosaccharide sequence through cleavage of the
      interglycosidic linkages was also possible, thus providing a sensitive and
      accurate tool for the structural verification of synthetic oligosaccharide
      intermediates.

PMID- 11527534
TI  - Stereoselective synthesis of methyl 4,6-O-benzylidene-2-C-methoxycarbonylmethyl
      alpha-D-ribo-hexopyranosid-3-ulose, and its X-ray crystallographic analysis.
AB  - Methyl 4,6-O-benzylidene-2-C-methoxycarbonylmethyl-alpha-D-ribo-hexopyranosid-3
      ulose has been stereoselectively synthesized in 65% yield by reaction of methyl
      4,6-O-benzylidene-alpha-D-arabino-hexopyranosid-2-ulose with diethyl malonate. X
      ray crystallographic structure analysis reveals that the chain-branch and the OH
      group are bonded to C-2 in axial and equatorial positions, respectively. The
      molecules in the crystal lattice are stacked along a one-dimensional chain, with
      intermolecular hydrogen bonds between O-8 of one molecule and 2-OH of the next as
      well as intramolecular hydrogen bonds between O-3 and 2-OH. All phenyl groups are
      parallel as well as the planes of sugar rings in the molecular columnar stacking.

PMID- 11527535
TI  - Stereospecific synthesis of beta-D-allopyranosides by dihydroxylation of beta-D
      erythro-2,3-dideoxyhex-2-enopyranosides.
AB  - The synthesis of 4,6-O-benzylidene-beta-D-erythro-2-3-dideoxyhex-2-enopyranosides
      and their osmium and ruthenium catalysed dihydroxylation reactions have been
      investigated. These reactions have been shown, for a range of monosaccharides and
      a disaccharide, to proceed stereospecifically to give beta-D-allopyranosides in
      moderate to excellent yield.

PMID- 11527536
TI  - Improved synthesis and characterization of 1,3,4,6-tetra-O-acetyl-2-(N
      acetylacetamido)-2-deoxy-beta-D-glucopyranose.
AB  - A method from the 1960s to synthesize the N,N-diacetyl derivative of
      peracetylated beta-D-glucosamine was improved by assistance of molecular sieves.
      The melting point of the title compound was revised and the structure determined
      by means of X-ray diffraction.

PMID- 11527538
TI  - Molecular cloning and functional expression of the guinea pig alpha(1a)
      adrenoceptor.
AB  - In the present paper, the cloning and expression of the guinea pig alpha(1A)
      adrenoceptor is presented. The nucleotide sequence had an open reading frame of
      1401 bp that encoded a 466 amino-acid protein with an estimated molecular mass of
      approximately 51.5 kDa. When the clone was expressed in Cos-1 cells, specific
      high-affinity binding of [(3)H]prazosin and [(3)H]tamsulosin was observed.
      Chloroethylclonidine treatment of membranes slightly decreased the total binding
      with both radioligands. Binding competition experiments using [(3)H]tamsulosin
      showed the following potency order: (a) for agonists: oxymetazoline
      >>epinephrine>norepinephrine>methoxamine, and (b) for antagonists: prazosin> or 5
      methyl-urapidil=benoxathian>phentolamine>>BMY 7378 (8-[2-[4-(2-methoxyphenyl)-1
      piperazinyl]ethyl]-8-azaspiro[4,5]decane-7,9-dione). Photoaffinity labeling using
      [(125)I-aryl]azido-prazosin revealed a major broad band with a molecular mass
      between 70 and 80 kDa. The receptor was functional, as evidenced by an
      epinephrine-increased production of [(3)H]inositol phosphates that was blocked by
      prazosin.

PMID- 11527540
TI  - Lack of evidence for cross-competition between vasoactive intestinal peptide and
      somatostatin at their respective receptors.
AB  - A possible cross-competition between vasoactive intestinal peptide (VIP) and
      somatostatin (somatotropin release inhibiting factor; SRIF) and their respective
      receptors, was investigated at native or recombinant SRIF and VIP/pituitary
      adenylate cyclase-activating polypeptide (PACAP) receptors. The activity of VIP
      was examined in radioligand binding assays at mouse sst(1-5), rat sst(1-2) and
      human sst(1-5) receptors; or at human tumours preferentially expressing each of
      the five SRIF receptors. Moreover, SRIF was investigated at human tumoral tissues
      known to exclusively express specific VIP/PACAP receptor(s). VIP had no
      significant effect on any of the radioligand binding sites of the SRIF receptor
      family of rat, mouse or human origin tested. Conversely, SRIF did not interfere
      with the human VIP/PACAP binding sites tested. Taken together, the results cast
      reservation on the claimed cross-competition between VIP and SRIF at,
      specifically human sst(3) receptors, or any of the cloned SRIF or VIP/PACAP
      receptors recognised to date.

PMID- 11527539
TI  - P2Y(11) receptor expression by human lymphocytes: evidence for two cAMP-linked
      purinoceptors.
AB  - The effects of extracellular ATP, ADP, AMP and adenosine on cAMP accumulation
      have been studied in freshly isolated B-lymphocytes from patients with chronic
      lymphocytic leukemia. Extracellular ATP and several nucleotide analogs stimulated
      cAMP accumulation with the following order of potency: ATP (EC(50)=120+/-20
      microM)>ADP>>AMP. ADP was less effective than ATP and may be a partial agonist.
      AMP exhibited variable but generally weak activity. The stable analog of ATP,
      alpha,beta-methylene ATP (EC(50)=110+/-15 microM) also stimulated cAMP
      accumulation and exhibited similar efficacy to ATP. The P2Y(2) receptor agonist,
      UTP had no effect on intracellular cAMP levels. Adenosine and the A(2A)/A(2B)
      receptor agonist, 5'-N-ethylcarboxamidoadenosine (NECA) also stimulated cAMP
      accumulation in CLL lymphocytes. Adenosine deaminase inhibited the cAMP response
      to adenosine but had no effect on the ATP-induced cAMP response. On the other
      hand, the AMP analog, adenosine 5'-thiomonophosphate, (AMPS; 1.0 mM) inhibited
      ATP-induced and alpha,beta-methylene ATP-induced cAMP production but had no
      effect on adenosine-induced cAMP production. Reverse transcriptase-polymerase
      chain reaction (RT-PCR) analysis revealed the presence of P2Y(11) receptor as
      well as A(2A) and A(2B) receptor mRNA in chronic lymphocytic leukemia
      lymphocytes. However, A(2B) receptors would appear to be relatively ineffective
      because the A(2A) selective agonist, CGS-21680 exhibited comparable efficacy to
      NECA. Furthermore, the A(2A)-selective antagonist 8-(3-chlorostyryl)-caffeine
      (CSC) right-shifted the concentration-response curve for NECA. Taken together,
      the data indicate that ATP induces cAMP accumulation via the activation of
      P2Y(11) receptors whereas adenosine induces cAMP accumulation via the activation
      of A(2A) receptors. Coordinate activation of P2Y(11) and A(2A) receptors may
      influence the developmental fate of normal B-lymphocytes.

PMID- 11527541
TI  - [(Dihydroindenyl)oxy]alkonic acid inhibits the cystic fibrosis transmembrane
      conductance regulator.
AB  - We investigated the effects of [(dihydroindenyl)oxy]alkaonic acid (DIOA) on the
      Cl(-) secretion in Calu-3 human airway epithelial cells that exclusively express
      the cystic fibrosis transmembrane conductance regulator (CFTR) as an apical Cl(-)
      channel. The 5'-nitro-2-(3-phenylpropylamino) benzoate (NPPB)-sensitive short
      circuit current (I(sc)) and apical conductance were markedly reduced by DIOA (100
      microM) in the presence and absence of isoproterenol (10 nM). Replacement of the
      butyl group in DIOA with a methyl group attenuated the inhibitory effects. The
      ED(50) of DIOA (17.0+/-1.0 microM) was almost equivalent to that of NPPB (15.6+/
      2.1 microM). In conclusion, DIOA inhibits CFTR as strongly as NPPB does.

PMID- 11527542
TI  - NMDA receptors are involved in dithiothreitol-induced hypothermia.
AB  - Sulfhydryl-reducing agents, such as dithiothreitol, modulate glutamate N-methyl-D
      aspartate (NMDA) receptors. Since these receptors are involved in
      thermoregulatory processes, we studied the effects of their positive modulation,
      through a dithiothreitol-induced reduction of the receptor redox site, on
      thermoregulation in rats maintained at an ambient temperature of 20-22 degrees C.
      Given intraperitoneally at the dose of 25 and 50 mg x kg(-1), dithiothreitol
      induced dose-dependent hypothermia. The prior administration of 0.5 mg x kg(-1)
      of (+/-)-dizocilpine maleate (MK801), a non-competitive glutamate NMDA receptor
      antagonist, blocked most of the dithiothreitol-induced hypothermia. MK801 given
      alone was followed by slight transient hyperthermia. This confirms the
      involvement of NMDA receptors in thermoregulation and suggests that they might be
      under redox modulation.

PMID- 11527543
TI  - Adenosine A(1) receptor agonism in the immature rat brain and heart.
AB  - We examined if the adenosine A(1) receptor agonist adenosine amine congener
      (ADAC, 100 microg/kg i.p.) is neuroprotective in 7-day-old rats subjected to
      hypoxic ischemia. Brain damage, evaluated as weight deficit and gross morphology,
      was not affected by ADAC treatment. Nonetheless, ADAC (100 microg/kg i.p.)
      reduced heart rate by 44% (p<0.0001), indicating that the dose given was
      pharmacologically active. Adenosine A(1) receptors were determined by [(3)H] 1,3
      dipropyl-8-cyclopentylxanthine (DPCPX)-binding and levels were 23% of the adult
      levels. GTP did not affect [(3)H] DPCPX-binding in the cerebral cortex at
      postnatal day 7 whereas there was strong enhancement of [(3)H] DPCPX-binding in
      the heart. This suggested a poor G-protein coupling at postnatal day 7 in the
      brain, which also was confirmed using GTP [gamma-(35)S]-binding in the presence
      of an adenosine A(1) receptor agonist. Thus, the lack of a neuroprotective effect
      of ADAC may be explained by the fact that adenosine A(1) receptors are not part
      of a functional unit in the 7-day-old rat brain.

PMID- 11527544
TI  - Effects of molsidomine on scopolamine-induced amnesia and hypermotility in the
      rat.
AB  - Nitric oxide (NO) is hypothesized to be a novel intracellular messenger in the
      central nervous system. Recently, NO involvement in learning and memory processes
      has been proposed. Compounds that inhibit nitric oxide synthase, the key
      synthesizing enzyme, may block cognition, while NO donors may facilitate it. The
      aim of this study was to assess in the rat the effects of the NO donor
      molsidomine (2 and 4 mg/kg, i.p.) on memory deficits caused by scopolamine. For
      this purpose, the object recognition task and the step-through passive avoidance
      procedure were chosen. In addition, the effects of molsidomine in antagonizing
      the scopolamine-induced hypermotility were also examined. Scopolamine at 0.2
      mg/kg (object recognition) and 0.75 mg/kg (passive avoidance) disrupted
      acquisition in both the tasks and induced locomotor hyperactivity at the dose of
      0.2 mg/kg. Molsidomine at either dose reversed the scopolamine-induced deficits
      in the object recognition paradigm but did not counteract the hypermotility and
      the deficits occurred in the passive avoidance test. These results suggest that
      to some extent, the NO donor molsidomine is involved in memory processing.

PMID- 11527545
TI  - Effects of bezafibrate on beta-cell function of rat pancreatic islets.
AB  - Bezafibrate is an activator of peroxisome proliferator-activated receptors (PPAR)
      alpha. The present study was performed to investigate the effects of bezafibrate
      and the PPAR alpha activator, 4-Cholro-6-(2.3-xylidino)-2-pyrimidin-ylthio acetic
      acid (WY14643), on the beta-cell function of rat pancreatic islets in vitro. In
      islets cultured with 300 microM bezafibrate or WY14643 for 8 h, a low glucose
      concentration induced insulin release and increased the levels of mRNA for PPAR
      alpha, acyl CoA oxidase, carnitine palmitoyl transferase-1, pyruvate
      dehydrogenase E1 alpha or pyruvate carboxylase. In contrast, after a 48-h culture
      period, a high glucose concentration induced insulin release and islet insulin
      content, but decreased the levels of mRNA for glucose transporter-2 (GLUT-2),
      preproinsulin or pancreatic/duodenal homeobox-1. Diazoxide, the KATP channel
      opener, restored these responses. We conclude that bezafibrate enhances insulin
      release through the activation of PPAR alpha gene expression during a short
      culture period, whereas it may contribute to beta-cell dysfunction through the
      mechanism of "excessive stimulation" during longer culture periods.

PMID- 11527548
TI  - Deficit in automatic sound-change detection may underlie some music perception
      deficits after acute hemispheric stroke.
AB  - Music perception deficits following acute neurological damage are thought to be
      rare. By a newly devised test battery of music-perception skills, however, we
      were able to identify among a group of 12 patients with acute hemispheric stroke
      six patients with music perception deficits (amusia) while six others had no such
      deficits. In addition we recorded event-related brain potentials (ERPs) in a
      passive listening task with frequent standard and infrequent pitch deviants
      designed to elicit the mismatch negativity (MMN). The MMN in the patients with
      amusia was grossly reduced, while the non-amusic patients and control subjects
      had MMNs of equal size. These data show that amusia is quite common in unselected
      stroke patients. The MMN reduction suggests that amusia is related to unspecific
      automatic stimulus classification deficits in these patients.

PMID- 11527547
TI  - The cannabinoid CB(1) receptor antagonist SR141716A increases norepinephrine
      outflow in the rat anterior hypothalamus.
AB  - The effects of the selective cannabinoid CB(1) receptor antagonist N-(piperidin-1
      yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide
      hydrochloride (SR141716A) on extracellular concentrations of norepinephrine and 5
      hydroxytryptamine (5-HT) were assessed by in vivo microdialysis in the anterior
      hypothalamus of freely moving rats. SR14716A (0.3, 1, 3 mg/kg, i.p.) dose
      dependently increased norepinephrine efflux to about 300% of baseline, without
      affecting 5-HT levels. This increase in norepinephrine outflow could play an
      important role in the pharmacological and potentially therapeutic actions of
      SR141716A.

PMID- 11527549
TI  - The role of argument structure in the production of nouns and verbs.
AB  - The study reports an investigation on the role of argument structure complexity
      in the production of nouns and verbs in three Italian agrammatic patients. The
      patients, all showing a clear noun/verb dissociation in the assessment tests,
      were requested to produce either nouns or verbs in a picture naming task. Four
      sets of words were selected to be produced in the naming task: non-argumental
      nouns (e.g., medaglia-medal), argumental nouns (e.g., pianto-crying), one-place
      argument verbs (e.g., dormire-to sleep), and two-place argument verbs (e.g.,
      sparare-to shoot). The performance of the three patients was almost identical.
      All made reliably fewer errors in the production of non-argumental nouns than in
      the production of verbs, thus replicating with the new materials the initially
      observed dissociation. Moreover, they made fewer errors with one-place than with
      two-place argument verbs, and with non-argumental than with argumental nouns.
      Finally, in contrast with the previously observed noun/verb dissociation, when
      their ability to produce argumental nouns and verbs was compared, no reliable
      difference was found. The results indicate that argument complexity may affect
      the ability of agrammatic patients to produce words. It is argued that since
      argument complexity is necessarily associated with verbs and only rarely with
      nouns, unless special attention is paid, argument complexity effects are easily
      confounded with grammatical class effects, possibly leading to erroneous
      interpretations of patients' performance.

PMID- 11527550
TI  - Context and crossover in unilateral neglect.
AB  - Patients with left-neglect bisect horizontal lines to the right of true center.
      Their bisection bias is affected by line length, so that longer lines are
      bisected further to the right. Patients often crossover and bisect very short
      lines to the left of true center. We tested the hypothesis that the context in
      which lines are apprehended accounts for the crossover phenomenon. We replicated
      previous findings that a line is bisected further leftward when it is preceded by
      a longer line and further rightward when it is preceded by a shorter line. These
      contextual effects occur with relatively short and relatively long target lines.
      Bisection patterns in two different series of lines, one ranging from 10 to 150
      mm, and the other from 110 to 250 mm, were investigated. If crossover bisections
      were simply due to contextual effects then left-sided errors would be observed on
      bisections of the shorter lines of both series. Our findings did not support this
      hypothesis. Crossover bisections occurred only with objectively short lines,
      those shorter than 40 mm. Even though we found significant contextual effects on
      line bisection biases, these effects per se do not account for the crossover
      phenomenon. Rather, our data suggest that the absolute length of the line is
      associated specifically with the crossover phenomenon.

PMID- 11527551
TI  - Two eyes make a pair: facial organization and perceptual learning reduce visual
      extinction.
AB  - We examined a patient with left spatial neglect and visual extinction due to
      right parietal damage in tasks where identical stimuli were presented before and
      after they were primed so as to be perceived as the eyes of schematic faces. In a
      first block, we presented alphanumeric stimuli (+, o, T, 6) on the right, left,
      or both sides of fixation on a blank background, and established that the patient
      could perceive unilateral stimuli on either side but extinguished most of the
      left-sided ones in the bilateral trials. In a second block, some of these stimuli
      (+, o) were presented again, but now in the position of eyes within the context
      of an oval frame which created the impression of a schematic face. Other stimuli
      (T, 6) were presented as previously on a blank background for an equal number of
      trials. In the third critical block, all stimuli were presented once again on a
      blank background, as in the first block. Now the patient extinguished very few of
      those left-sided stimuli primed to be seen as a pair of eyes in face
      configuration (+, o), but still extinguished most of the other stimuli (T, 6). A
      second control experiment showed no effect of repeatedly exposing stimuli in a
      common region of space defined by meaningless shape boundaries. These results
      suggest that facial organization can group eye features before the level where
      attentional selection or extinction occurs, and that such grouping may be
      influenced by rapid perceptual learning.

PMID- 11527552
TI  - Clinical validity of the 'mini-mental state' for Spanish speaking communities.
AB  - The Mini-Mental State (MMS) is a brief structured test of cognitive function. The
      purpose of this study was to adapt and normalise MMS for the Spanish population.
      The test was administered to 450 subjects (253 control volunteers, 86 mild
      memory/cognitive impairment without dementia subjects - CIWD and 111 Alzheimer's
      Disease patients - AD). A cross-sectional statistical study in a population
      stratified by age and education was conducted. A more accurate diagnosis is
      provided by scores that have been adjusted for age and level of education. The
      recommended cut-off in our study was 24/25 (non-demented above 24). The
      adaptation and normalisation of MMS provides the Spanish population with a highly
      valuable screening tool.

PMID- 11527553
TI  - Assessment of handedness using a digitizing tablet: a new method.
AB  - The assessment of handedness is of interest in some psychiatric populations,
      above all in schizophrenic patients, because there may be a relationship between
      neurodevelopmental, hemispheric damage and psychiatric disease processes (Crow
      TJ. Schizophrenia Bulletin 1990;16:433-443; Tyler M, Diamond J, Lewis S.
      Schizophrenia Research 1995;18:37-41). Various methods to assess handedness have
      been proposed. In order to detect the most precise instrument for the assessment
      of handedness, two different measures, a questionnaire and a computational
      procedure for movement analysis, were compared in a group of healthy subjects.
      The ability of the methods to discriminate not only between the groups of right
      handers (n=12) and left-handers (n=23), but also between left-handers trained in
      school to use the non-dominant right hand ('inconsistent' left-handers; n=11) and
      those allowed to use their left hand for writing ('consistent' left-handers;
      n=12) was investigated. For future investigations, our main concern was to
      determine if one method had superiority over the other. The results revealed that
      the Edinburgh Handedness Inventory (EHI) distinguishes just as well as the
      computational method between right-handers and non-right-handers. However, more
      precise discrimination between the subgroups of 'consistent' and 'inconsistent'
      left-handers is possible using digitized analysis of hand-motor performance.
      According to our results handedness should be assessed not only with the EHI, but
      also with the computer-aided analysis of hand-movements.

PMID- 11527554
TI  - Brain activation during automatic and controlled processing of semantic
      relations: a priming experiment using lexical-decision.
AB  - Semantic relations may be studied using the experimental technique known as
      semantic priming, in which a word 'primes' the processing of a related target
      (e.g. lion-tiger), following a short delay. Priming may be automatic or, with
      longer delays, under more controlled processing. This study used functional
      magnetic resonance imaging (fMRI) to examine the cerebral activation during two
      lexical-decision semantic priming experiments, with a short and long delay,
      representing automatic and controlled processing, respectively. A further two un
      primed lexical-decision tasks were performed to distinguish cerebral activation
      specific to semantic priming itself from those utilised during lexical-decision
      processes. Distinct regions of anterior cingulate cortex (ACC) were critical to
      automatic and controlled semantic priming, whilst the putamen and hippocampal
      complex responded differently to unrelated and semantically related prime-target
      pairs. Lexical-decision alone revealed activation in posterior temporal cortex
      especially on the left, in agreement with previous neuroimaging studies. The
      results provide a plausible neural substrate for common semantic relations
      independent of task demands and further emphasise the regional functional
      specialisation of the ACC.

PMID- 11527555
TI  - Contralesional directional hypermetria associated with line bisection-specific
      ipsilesional neglect.
AB  - Patients with contralesional neglect from right hemisphere injuries often fail to
      be aware of or respond to visual stimuli in the left hemispace. In contrast,
      other patients with right hemisphere damage rarely demonstrate behavior
      consistent with task-specific ipsilesional neglect (IN). We performed a series of
      experiments in a patient with IN on a line bisection task after a right frontal
      infarct. When asked to perform horizontal limb movements without visual feedback,
      the patient showed a leftward directional hypermetria. Similar performance was
      also observed during a representational production of a given distance without
      sensory input. These results suggest that IN is induced by a directional
      hypermetria resulting from disruption of the motor-intentional system.

PMID- 11527556
TI  - Sensation seeking correlates of passive auditory P3 to a single stimulus.
AB  - A single auditory stimulus in a passive ignore condition elicits a P3 potential
      (passive P3) that shares similar morphology with the classical P3 (P300 or P3b)
      in the active auditory 'oddball' paradigm. Since the classical P3 is correlated
      with introversion, anxiety, or sensation seeking, it was hypothesized that the
      passive P3 is correlated with sensation seeking personality. Therefore, 39
      healthy subjects aged from 15 to 57 years and free from depression, were asked to
      answer Zuckerman's sensation seeking scales (SSS), and undergo an auditory event
      related potential procedure with a single stimulus. In all subjects, a clear
      passive P3 appeared at three midline electrodes that shared similar latency and
      amplitude to the classical P3. The SSS total and experience seeking subscale
      scores were positively correlated with N1 amplitude at Fz. In contrast, the SSS
      total and some subscale scores were negatively correlated with the passive P3
      amplitudes at the three electrodes. The sensation seeking personality effects on
      the passive P3 might be via a cortical inhibition process during memory updating,
      which are considered to be involved in the classical P3.

PMID- 11527557
TI  - Impaired speech perception in aphasic patients: event-related potential and
      neuropsychological assessment.
AB  - The mismatch negativity component (MMN) of auditory event-related potentials
      (ERP) was recorded in four aphasic patients and in age, gender and education
      matched controls. The MMN changes elicited by tone, vowel, voicing stop consonant
      and place-of articulation contrasts were recorded over both hemispheres. The
      results of MMN amplitude, latency and distribution differences between aphasics
      and controls were analyzed in detail. An extensive neuropsychological
      investigation was performed in order to highlight the assumed dissociation and
      possible interactions between the impaired acoustic/phonetic perception and
      deficient comprehension in aphasic patients. Our principal finding was that MMN
      elicited by pitch deviations is not enough sensitive to distinguish between
      patients and age-matched controls. The MMN elicited by consonant contrasts was
      found to be the most vulnerable in aphasic patients investigated. The MMN
      elicited by voicing ([ba:] vs. [pa:]) and place-of-articulation ([ba:] vs. [ga:])
      could be characterized by total lack, distorted or very limited distribution and
      correlated with the patients' performance shown in the behavioral phoneme
      discrimination task. The magnitude of the deficient phoneme (vowel and consonant
      contrasts) processing shown by MMN anomalies was proportionally related to the
      non-word discrimination and did not interact with the word discrimination
      performance. The impact of deficient speech sound processing on higher level
      processes may depend on the type of aphasia, while the presence of perceptual
      deficits in processing acoustic/phonetic contrasts seems to be independent of the
      type of aphasia.

PMID- 11527558
TI  - Distinct patterns of word retrieval in right and left frontal lobe patients: a
      multidimensional perspective.
AB  - Several studies have shown that patients with frontal lobe damage (FL) generate
      fewer words than control participants in verbal fluency tasks. In the current
      study, we were interested in assessing the quality of such verbal fluency data.
      Multidimensional exploratory techniques, namely, hierarchical clustering (HC) and
      correspondence analysis (CoA), were performed on verbal fluency data collected
      from 13 FL patients and 11 age-matched controls. HC of individual word-profiles
      distinguished between patients with left frontal lobe (LFL) and right frontal
      lobe (RFL) lesions. CoA revealed that LFL patients generated unusual word
      profiles, as evidenced by their peripheral location on a CoA map, while RFL
      patients produced highly typical word-profiles. We would like to suggest that
      preserved functioning of the left frontal lobe might have constrained the
      responses of the RFL group resulting in typical word combinations, whereas
      preserved right frontal lobe functioning might have mediated greater
      diversification in the responses of the LFL group. The present study shows that
      HC and CoA can be applied to neuropsychological data to reveal complex
      relationships between cognitive performance and cerebral lesion sites.

PMID- 11527559
TI  - Are Alzheimer's disease patients able to learn visual prototypes?
AB  - Recently, controversial results emerged regarding visual prototype learning in
      Alzheimer's disease (AD). The aim of this study was to elucidate this issue in a
      larger population of AD patients. The AD patients (N=72) and age-matched healthy
      control subjects (N=25) learned to recognize and to categorize visual dot
      patterns. In comparison with the control subjects, the AD patients as a group
      showed dysfunctions in the recognition task, whereas categorization was
      relatively spared in their case. Recognition was impaired in patients with mild
      AD (Mini-Mental score: 18-23) and moderate AD (Mini-Mental score<18), whereas
      categorization was impaired only in patients with moderate AD. These results
      suggest that while the medio-temporal/diencephalic explicit memory system is
      markedly affected even in early AD, the sensory neocortical areas mediating
      implicit category learning display a sufficient degree of functional capacity
      until later stages of the disease.

PMID- 11527560
TI  - Spared numerical abilities in a case of semantic dementia.
AB  - We report a case study of a patient (IH) with a progressive impairment of
      semantic memory affecting all categories of knowledge apart from numbers.
      Pictorial material was better understood than words, but was still severely
      impaired. The selective preservation of nearly all aspects of numerical knowledge
      suggested that this domain might have different neuropsychological status from
      other aspects of semantic memory.

PMID- 11527562
TI  - Prism adaptation improves representational neglect.
AB  - Previous work has shown that various symptoms of unilateral neglect, including
      the pathological shift of the subjective midline to the right, may be improved by
      a short adaptation period to a prismatic shift of the visual field to the right.
      We report here, in two neglect patients the improvement of imagery neglect after
      prism exposure. Despite a strong neglect observed for mental images, as well as
      for conventional tests, the mental evocation of left-sided information from an
      internal image of the map of France was fully recovered following prism
      adaptation to the right. This improvement could not be explained by the
      alteration of visuomotor responses induced by the prism adaptation. Therefore,
      prism adaptation may act not only on sensory-motor levels but also on a higher
      cognitive level of mental space representation and/or exploration.

PMID- 11527561
TI  - Automatic orienting of visuospatial attention in Parkinson's disease.
AB  - The basal ganglia are involved in not only motor behavior, but also other more
      cognitive processes, such as attention. We tested Parkinson's disease (PD)
      patients in a task that measures reflexive orienting of spatial attention. Seven
      patients with idiopathic PD and eight control subjects performed a covert
      orienting task where spatial attention was directed by means of exogenous cues
      (luminance increments) with no predictive validity for target position. The
      subjects' task was to make a speeded saccade to a visual target, which appeared a
      variable time after onset of the cue either in the cued or an uncued spatial
      position. There was no overall difference between PD patients and control
      subjects in terms of the initial facilitation following reflexive cues, and later
      inhibition of return (IOR). However, PD patients differed from control subjects
      in two important respects. First, they were significantly faster than were
      control subjects on this reflexive visual-orienting task. Second, disease
      severity correlated with attentional performance; more advanced patients showed
      less initial facilitation but greater IOR. Thus PD patients show better
      performance on a reflexive saccade task and, for more advanced patients, greater
      IOR than control subjects. These findings are consistent with the possibility
      that reflexive attentional processes in PD patients may be more active.

PMID- 11527563
TI  - Evaluation of the cytotoxicity, mutagenicity and antimutagenicity of emerging
      edible plants.
AB  - This study evaluates the toxic, mutagenic and antimutagenic effects of emerging
      edible plants that are consumed as new leafy vegetables in Taiwan. Among eight
      plant extracts, only the extracts of Sol (Solanum nigrum L.) showed cytotoxicity
      to Salmonella typhimurium TA100 in the absence of S9 mix. The toxicity of
      extracts from different parts of the Sol plant, such as leaf and stem, immature
      fruit and mature fruit, towards S. typhimurium TA100 and human lymphocytes was
      also assayed. The immature fruit extracts of Sol exhibited strong cytotoxicity
      with dose dependence and induced significant DNA damage in human lymphocytes
      based on the comet assay. However, no mutagenicity was found in eight plant
      extracts to TA98 or TA100 either with or without the S9 mixture. Sol and Sec
      [Sechium edule (Jacq.) Swartz] extracts showed the strongest inhibitory effect
      towards the mutagenicity of 2-amino-3-methyl-imidazo[4,5-f]quinoline (IQ) in S.
      typhimurium TA98 and TA100; the ID(50) was less then 1 mg/plate. Cra
      [Crassocephalum creidioides (Benth.) S. Moore] extracts also expressed moderate
      antimutagenic activities towards IQ and benzo[a]pyrene (B[a]P) either in TA98 or
      in TA100; the ID(50) was 1.63-2.41 mg/plate. The extracts from Bas (Basella alba
      L.), Bou (Boussingaultia gracilis Miers var. pseudobaselloides Bailey), Cen
      (Centella asiatica L. Urban), Cor (Corchorus olitorius L.) and Por (Portulaca
      oleracea L.) showed weak to moderate inhibition of mutagenicity of IQ. However,
      the potential antimutagenicity of these plant extracts towards B[a]P was weaker
      than that towards IQ. For a direct mutagen, 4-nitroquinoline-N-oxide (NQNO), only
      the Sol extracts showed strong inhibitory effects in the TA100 system. The
      antimutagenic activity of water extracts of Sec was partly reduced by heating at
      100 degrees C for 20 min. The heat-stable antimutagens in Sec extracts could be
      produced in the plant extract preparation process. Fractions with molecular
      weights above 30,000 showed the strongest antimutagenicity and peroxidase
      activity in all the fractions of the Sec extracts.

PMID- 11527564
TI  - Assessment of cancer risk from ethylene oxide residues in spices imported into
      New Zealand.
AB  - Quantitative estimates of cancer risks from ethylene oxide (ETO) residues were
      constructed based on 200 retail samples of various spices in New Zealand. Two
      samples of cinnamon contained detectable ETO. The highest value encountered was
      15 ppm. ETO was not detected in the remaining 198 samples. However, 31 samples
      had detectable levels of ethylene chlorohydrin (ECH) and/or ethylene bromohydrin
      (EBH). A conservative estimate of ETO intake, based on average spice consumption,
      was 3.4 x 10(-6) mg/kg/day. Cancer potency factors for ETO ranging from 0.29 to
      0.55 (mg/kg/day)(-1) were used to form cancer risk estimates. The resulting
      estimates of average lifetime excess cancer risk was 0.8 x 10(-6) to 1.7 x 10(
      6). The US 97.5 percentile value for spice consumption (2.8 kg spices per year),
      gave an extreme upper-end estimate of lifetime cancer risk of approximately 1.4 x
      10(-5). These risks are practically negligible considering the conservative
      assumptions used in estimating exposure to ETO. The exposures to ECH and EBH are
      200-300-fold higher than to ETO. These compounds are of lesser potency to ETO in
      terms of mutagenicity or carcinogenicity in studies to date. However, the precise
      contribution of these compounds to the cancer risk estimate is uncertain due to
      large toxicological data gaps, including the absence of a 2-year cancer bioassay
      by the oral route.

PMID- 11527565
TI  - Subchronic toxicity study of gallic acid by oral administration in F344 rats.
AB  - Subchronic toxicity of gallic acid (GA) was investigated in F344 rats by feeding
      diet containing 0, 0.2, 0.6, 1.7 and 5% GA for 13 weeks. Each group consisted of
      10 rats of each sex. Toxicological parameters included clinical signs, body
      weight, food consumption, hematology, blood biochemistry, organ weights and
      histopathological assessment. Body weight gain in the 5% GA-treated animals of
      both sexes from week 1 to the end of the experiment was significantly lower than
      that of the untreated controls. Toxic effects following administration of 0.6% or
      more in males and 5% in females included reduction of hemoglobin concentration,
      hematocrit and red blood cell counts and increase in reticulocytes.
      Histopathologically, extramedullary hematopoiesis, hemosiderin deposition and
      congestion appeared in the spleens of 5% GA-treated animals, suggesting
      development of hemolytic anemia. In addition, centrilobular liver cell
      hypertrophy, reflected in increase in liver weight, was observed in animals of
      both sexes from 1.7%. In the kidney, Berlin blue-negative brown pigment
      deposition in the proximal tubular epithelium was observed at 5% GA. However, the
      severity of these pathological changes was weak. Based on the present toxicology
      data, 0.2% was determined to be a no-observed-adverse-effect level (NOAEL) in
      rats. This level was translated into 119 and 128 mg/kg/day, respectively for male
      and female rats.

PMID- 11527566
TI  - Instability of N-acetylated fumonisin B1 (FA1) and the impact on inhibition of
      ceramide synthase in rat liver slices.
AB  - Fumonisin B1 (FB1) is a mycotoxin produced by Fusarium verticillioides. It
      inhibits ceramide synthase, which is a proposed underlying mechanism responsible
      for the myriad of toxic endpoints observed. We previously reported that N
      acetylation of FB1 prevents ceramide synthase inhibition, but cautioned that
      impure preparations of FA1 can contain a contaminant with the ability to inhibit
      ceramide synthase. We now report that FA1 spontaneously rearranges to O
      acetylated analogs. These rearrangement products are putative inhibitors of
      ceramide synthase. Rat liver slices exposed to impure FA1 containing O-acetylated
      FB1 had sphinganine/sphingosine (Sa:So) ratios of 1.15-1.64. Control slices had
      Sa:So ratios of 0.07-0.24. Clean-up to remove the O-acetylated FB1 yielded
      purified FA1, which produced Sa:So ratios in liver slices of 0.08-0.18. After
      storage for approximately 1 year as either a dry powder in a desiccator, or as a
      dried film at 4 degrees C, the purified FA1 again contained O-acetylated FB1, and
      was capable of ceramide synthase inhibition. FA1 was most stable in neutral
      solution, but in acidic solution the equilibrium shifted towards the O-acetylated
      forms. FA1 in solid form also rearranged, but more slowly than in acid solution.
      As FA1 is considerably less cytotoxic than FB1, these results provide additional
      support for the conclusion that a primary amino group is necessary for both
      ceramide synthase inhibition and toxicity.

PMID- 11527567
TI  - Regional variations in skin barrier function and cutaneous irritation due to
      iontophoresis in human subjects.
AB  - The effect of saline iontophoresis on skin barrier function and irritation was
      investigated on three body sites (abdomen, chest and upper arm) in order to
      select an appropriate site for iontophoretic delivery of drugs. Thirty healthy
      human volunteers were recruited according to specific entry criteria. Ten
      subjects, five males and five females, were assigned to each body site group.
      Skin barrier function and irritation was examined after 4 h of saline
      iontophoresis at a current density of 0.2 mA/cm(2) on a 6.5 cm(2) area in terms
      of the measured responses: transepidermal water loss (TEWL), skin capacitance,
      skin temperature and visual scores. Alterations in TEWL due to iontophoresis were
      not observed in the upper arm and chest; however, changes in TEWL at the abdomen
      were observed and returned to baseline 2 h after patch removal. Similarly,
      changes in capacitance due to iontophoresis returned to baseline (P>0.05) at the
      three body sites 2 h after patch removal except under the anode at the abdomen
      (P<0.05). There was a significant increase in skin temperature due to
      iontophoresis at the anode and the cathode (P<0.05) at the upper arm. Edema was
      not observed. At patch removal, the erythema score was significantly (P<0.001)
      elevated in comparison to baseline at the three body sites. Erythema resolved
      within 24 h except at the chest under the anode, where the erythema score was
      still higher (P<0.01) than the baseline. Papules appeared in five subjects at the
      active anode site on the chest. In three of the subjects, these papules did not
      resolve until 24 h post patch removal. Thus, there was regional variation in the
      function of the skin and irritation due to iontophoresis. Irritation was greater
      at the chest than at the abdomen or upper arm.

PMID- 11527568
TI  - Immunotoxicity of a standardized citrus polymethoxylated flavone extract.
AB  - Polymethoxylated flavones (PMFs) from citrus inhibit production of TNF-alpha and
      other pro-inflammatory cytokines. As TNF-alpha also modulates NK cell activity,
      the current studies were conducted to assess the potential for a standardized
      citrus PMF mixture to suppress humoral and innate immune functions. PMFs were
      isolated from orange peel oil using a procedure that obtained a consistent
      mixture of PMFs both in identity and proportion. The mixture consisted of
      nobiletin (30.7%), 3,3',4',5,6,7,8-heptamethoxyflavone (27.9%),
      trimethylscutellarein (14.5%), tangeretin (10.4%), sinensetin (5.8%), 5-demethyl
      nobiletin (2.0%), hexa-O-methylquercetagetin (1.3%), 5-demethyl
      tetramethylscutellarein (0.6%), and other flavonoids (2.7%). To assess the effect
      of the PMF mixture on humoral immune responses, female B(6)C(3)F(1) mice (n=8)
      were exposed to the PMF by gavage at 5, 50, 150 and 500 mg/kg/day for 28 days. On
      day 25, mice were sensitized to sRBC by tail vein injection and AFC response
      determined 4 days later. Humoral immunity was insensitive to suppression
      following exposure to all concentrations of the PMF mixture. Suppression of NK
      cell activity was observed only following 500 mg/kg/day for 28 days. Body weights
      were not affected by exposure to any concentration of the PMF mixture in sRBC
      immunized or non-immunized mice. However, in sRBC-immunized mice, higher
      concentrations of PMF were associated with a statistically insignificant increase
      in spleen weight (P>0.05). No change in spleen weight was observed in non
      immunized mice. As anticipated, based on previously published in vitro
      observations, long-term, high-dose exposure to a standardized mixture of citrus
      PMFs caused a mild suppression of NK cell activity; however, humoral immunity was
      not sensitive to suppression at the same exposure levels.

PMID- 11527569
TI  - Allergic contact dermatitis elicitation thresholds of potent allergens in humans.
AB  - Literature scoured for human allergenicity to individual chemicals yields a
      limited number of potent sensitizers, which can be classified in four categories:
      metals, botanicals, biocides and miscellany. Potency is defined as strong for
      substances eliciting eczematous reactions to patch concentrations of 500 ppm
      (parts per million) or less in sensitized individuals. Most data encountered stem
      from studies conducted on dermatology patients tested routinely for
      hypersensitivity; only few data have been generated by systematic serial dilution
      testing.

PMID- 11527570
TI  - Ornithine decarboxylase and thymidine kinase activities and polyamine levels from
      selected organs of adult miniature swine receiving three concentrations of
      dietary menhaden oil.
AB  - Mature, female swine were randomly assigned to one of seven dietary groups. Swine
      in groups 1-3 were fed a cholesterol-rich diet for 55 days while the remaining
      groups remained on a basal swine diet. At the end of the cholesterol(Chol)
      preloading period the swine in groups 1-7 were placed on menhaden oil (MO) and/or
      corn oil (CO) as follows: groups 1 and 4, 15% CO (control); groups 2 and 5, 0.75%
      MO+14.25% CO; groups 3 and 7, 15% MO; and group 6, 7.5% MO+7.5% CO. Animals were
      killed at the end of the approximately 6-month feeding period and portions of
      liver, pancreas and colon mucosa were analyzed for both ornithine decarboxylase
      (ODC) and thymidine kinase (TK) activity while polyamine levels were measured in
      the liver and pancreas. Statistical analyses were carried out by one-way and two
      way ANOVA and by trend analysis. In the pancreas, the highest MO group (group 7)
      had significantly higher ODC levels when compared with the CO control (group 4)
      and the next to highest MO group (group 6) (one-way ANOVA)-all non-cholesterol
      preloaded groups. Using a two-way ANOVA (Chol-by-MO), liver ODC was significantly
      lower in the CO control when compared with the lowest and highest MO groups
      (groups 5 and 7, respectively), again in the non-cholesterol-preloaded animals.
      In the colon, the swine in the Chol-low MO group (group 2) had significantly
      lower TK activity than the Chol/CO control group (group 1) and Chol/Hi MO group
      (group 3) (one-way ANOVA) and also had significantly lower activity than all
      groups except the CO control (group 4) (two-way ANOVA). Liver acetylputrescine in
      the lowest and highest MO groups (groups 5 and 7, respectively) was significantly
      higher than in the CO group (group 4). Liver spermidine in the Chol-Hi MO group
      (group 3) was significantly higher than the Chol-Lo MO group (group 2), while the
      highest MO group (group 7) had a statistically higher level than the other non
      cholesterol groups (groups 4-6) (one-way ANOVA). Liver spermine was significantly
      higher in the Chol-Hi MO group (group 3) when compared to the CO control (group
      1) and the Chol-Lo MO group (group 2) (one-way ANOVA). Pancreatic putrescine in
      the CO control (group 4) was significantly higher than all other groups (two-way
      ANOVA) while spermine from the 2 Chol-MO groups (groups 2 and 3) was higher than
      the Chol-CO control (group 1) (one-way ANOVA). Using trend analysis, liver TK,
      putrescine and spermidine increased in the non-cholesterol preloaded groups with
      increasing dietary MO, similar to the increase seen in ODC. Thus, of the three
      organs studied, only liver responded to menhaden oil with changes in both ODC
      itself or some of its metabolic engendered products and thymidine kinase; at
      least for one of the parameters, ODC, change associated with dietary MO was
      dependent on whether the swine were preloaded with cholesterol.

PMID- 11527571
TI  - Inactivation of cytochrome P450 by the food-derived complex phenol oleuropein.
AB  - Complex phenols, such as the glycoside oleuropein and hydroxytyrosol, are found
      in high concentrations in the typical components of the Mediterranean diet. We
      have previously reported that oleuropein inhibits androstenedione 6 beta
      hydroxylase activity, a CYP3A marker in human liver microsomes (Stupans, I.,
      Stretch, G., Hayball, P., 2000. Olive oil phenols inhibit human hepatic
      microsomal activity. Journal of Nutrition. 130 2367-2370). Oleuropein, but not
      the structurally similar compounds hydroxytyrosol and secologanin, was found to
      be a mechanism-based inhibitor of androstenedione 6 beta-hydroxylase activity.
      Preincubation with 100 microM oleuropein and NADPH resulted in a significantly
      lower androstenedione 6 beta-hydroxylase activity when compared to preincubation
      carried out with oleuropein without NADPH, 0.11+/-0.01 nmol/mg microsomal
      protein/min compared with 0.29+/-0.03 nmol/mg microsomal protein/min (P<0.05).
      The inactivation exhibited pseudo-first-order kinetics. The maximal rate constant
      for inactivation (k(inactivation)) was calculated to be 0.09 min(-1) and the
      concentration of inactivator required for half maximal inactivation (Ki) was
      calculated to be 22.2 microM. Oleuropein was found to be a relatively weak
      inhibitor of CYP1A2-mediated 7-methoxyresorufin-O-deethylation (24% inhibition at
      100 microM oleuropein), but not CYP2E1-mediated chlorzoxazone 6-hydroxylation.
      CYP1A2 did not undergo mechanism-based inactivation by oleuropein.

PMID- 11527572
TI  - Long-term depression: a cascade of induction and expression mechanisms.
AB  - The aims of this paper are to provide a comprehensive and up to date review of
      the mechanisms of induction and expression of long-term depression (LTD) of
      synaptic transmission. The review will focus largely on homosynaptic LTD and
      other forms of LTD will be considered only where appropriate for a fuller
      understanding of LTD mechanisms. We shall concentrate on what are felt to be some
      of the most interesting recent findings concerning LTD in the central nervous
      system. Wherever possible we shall try to consider some of the disparities in
      results and possible reasons for these. Finally, we shall briefly consider some
      of the possible functional consequences of LTD for normal physiological function.

PMID- 11527573
TI  - Non-genomic effects of glucocorticoids in the neural system. Evidence, mechanisms
      and implications.
AB  - Complementing the classical concept of genomic steroid actions, here we (i)
      review evidence showing that important neural effects of glucocorticoids are
      exerted by non-genomic mechanisms; (ii) describe known mechanisms that may
      underlie such effects; (iii) summarize the functions and implications of non
      genomic mechanisms and (iv) outline future directions of research. The role of
      non-genomic mechanisms is to shape the response of the organism to challenges
      that require a substantial reorganization of neural and somatic functions and
      involve massive behavioral shifts. Non-genomic effects may (i) prepare the cell
      for subsequent glucocorticoid-induced genomic changes, (ii) bridge the gap
      between the early need of change and the delay in the expression of genomic
      effects and (iii) may induce specific changes that in some instances are opposite
      to those induced by genomic mechanisms. The latter can be explained by the fact
      that challenging situations require different responses in early (acute) and
      later (chronic) phases. Data show that non-genomic mechanisms of glucocorticoid
      action play a role in both pathological phenomena and the expression of
      ameliorative pharmacological effects. Non-genomic mechanisms that underlie many
      glucocorticoid-induced neural changes constitute a for long overlooked
      controlling factor. Despite the multitude and the variety of accumulated data,
      important questions remain to be answered.

PMID- 11527574
TI  - The multifaceted roles of glycogen synthase kinase 3beta in cellular signaling.
AB  - Glycogen synthase kinase-3beta (GSK3beta) is a fascinating enzyme with an
      astoundingly diverse number of actions in intracellular signaling systems.
      GSK3beta activity is regulated by serine (inhibitory) and tyrosine (stimulatory)
      phosphorylation, by protein complex formation, and by its intracellular
      localization. GSK3beta phosphorylates and thereby regulates the functions of many
      metabolic, signaling, and structural proteins. Notable among the signaling
      proteins regulated by GSK3beta are the many transcription factors, including
      activator protein-1, cyclic AMP response element binding protein, heat shock
      factor-1, nuclear factor of activated T cells, Myc, beta-catenin, CCAAT/enhancer
      binding protein, and NFkappaB. Lithium, the primary therapeutic agent for bipolar
      mood disorder, is a selective inhibitor of GSK3beta. This raises the possibility
      that dysregulation of GSK3beta and its inhibition by lithium may contribute to
      the disorder and its treatment, respectively. GSK3beta has been linked to all of
      the primary abnormalities associated with Alzheimer's disease. These include
      interactions between GSK3beta and components of the plaque-producing amyloid
      system, the participation of GSK3beta in phosphorylating the microtubule-binding
      protein tau that may contribute to the formation of neurofibrillary tangles, and
      interactions of GSK3beta with presenilin and other Alzheimer's disease-associated
      proteins. GSK3beta also regulates cell survival, as it facilitates a variety of
      apoptotic mechanisms, and lithium provides protection from many insults. Thus,
      GSK3beta has a central role regulating neuronal plasticity, gene expression, and
      cell survival, and may be a key component of certain psychiatric and
      neurodegenerative diseases.

PMID- 11527575
TI  - A stochastic, molecular model of the fission yeast cell cycle: role of the
      nucleocytoplasmic ratio in cycle time regulation.
AB  - We propose a stochastic version of a recently published, deterministic model of
      the molecular mechanism regulating the mitotic cell cycle of fission yeast,
      Schizosaccharomyces pombe. Stochasticity is introduced in two ways: (i) by
      considering the known asymmetry of cell division, which produces daughter cells
      of slightly different sizes; and (ii) by assuming that the nuclear volumes of the
      two newborn cells may also differ. In this model, the accumulation of cyclins in
      the nucleus is proportional to the ratio of cytoplasmic to nuclear volumes. We
      have simulated the cell-cycle statistics of populations of wild-type cells and of
      wee1(-) mutant cells. Our results are consistent with well known experimental
      observations.

PMID- 11527576
TI  - A model of oxidative phosphorylation in mammalian skeletal muscle.
AB  - A dynamic computer model of oxidative phosphorylation in oxidative mammalian
      skeletal muscle was developed. The previously published model of oxidative
      phosphorylation in isolated skeletal muscle mitochondria was extended by
      incorporation of the creatine kinase system (creatine kinase plus
      phosphocreatine/creatine pair), cytosolic proton production/consumption system
      (proton production/consumption by the creatine kinase-catalysed reaction,
      efflux/influx of protons), physiological size of the adenine nucleotide pool and
      some additional minor changes. Theoretical studies performed by means of the
      extended model demonstrated that the CK system, which allows for large changes in
      P(i) in relation to isolated mitochondria system, has no significant influence on
      the kinetic properties of oxidative phosphorylation, as inorganic phosphate only
      slightly modifies the relationship between the respiration rate and [ADP].
      Computer simulations also suggested that the second-order dependence of oxidative
      phosphorylation on [ADP] proposed in the literature refers only to the ATP
      synthesis flux, but not to the oxygen consumption flux (the difference between
      these two fluxes being due to the proton leak). Next, time courses of changes in
      fluxes and metabolite concentrations during transition between different steady
      states were simulated. The model suggests, in accordance with previous
      theoretical predictions, that activation of oxidative phosphorylation by an
      increase in [ADP] can (roughly) explain the behaviour of the system only at low
      work intensities, while at higher work intensities parallel activation of
      different steps of oxidative phosphorylation is involved.

PMID- 11527577
TI  - Classification of CD and absorption spectra in the Soret band of H(2)TMPyP bound
      to various synthetic polynucleotides.
AB  - The binding mode of porphyrins, namely meso-tetrakis(N-methyl pyridinium-4
      yl)porphyrin (H(2)TMPyP), was classified in this work by absorption and circular
      dichroism(CD) spectroscopy. The three binding modes of intercalation, minor
      groove binding and external stacking exhibit their own characteristic absorption
      and CD spectra. Intercalation occurs for this porphyrin when bound to GC-rich
      polynucleotides at a low mixing ratio, as expected. This binding mode produces
      hypochromism and a red shift in the absorption band and a negative CD band in the
      Soret absorption region. When it is complexed with AT-rich polynucleotides at a
      low mixing ratio, hypochromism and a red shift in the absorption band and a
      positive CD peak is apparent, and this species can easily be assigned to the
      minor groove-binding mode. For both AT- and GC-rich polynucleotides at a high
      binding ratio, an excitonic CD was apparent. The sign of excitonic CD depends on
      the order of the DNA bases; the CD spectra of H(2)TMPyP complexed with non
      alternating homopolymer (disregarding the nature of base pairs, i.e. AT or GC)
      are characterized by a positive band at short wavelengths followed by a negative
      band at long wavelengths. In contrast, those complexed with alternating
      polynucleotide were opposite to those of non-alternating homopolymers.

PMID- 11527578
TI  - Path finding by tube morphogenesis in an amoeboid organism.
AB  - We have studied how the plasmodium of Physarum polycephalum, a large amoeboid
      cell, is able to track the shortest path between two selected points in a
      labyrinth. When nutrients are supplied at these points to a sheet-like plasmodium
      extended fully in a maze, the organism forms a single tube which connects the two
      sites via the shortest route. During the path finding, plasmodial parts in dead
      ends of the maze shrink and finally the tube with the minimum-length is selected
      from the existing possibilities. A simple cellular mechanism based on interacting
      cellular rhythms may describe the experimental observations.

PMID- 11527579
TI  - Influence of allosteric effectors on the kinetics and equilibrium binding of
      phosphoenolpyruvate (PEP) to phosphoenolpyruvate carboxylase (PEPC) from Zea
      mays.
AB  - Phosphoenolpyruvate carboxylase (PEPC) the carbon dioxide processing enzyme of
      C(4) plants, shows the features of an allosteric enzyme. Allosteric activators
      such as D-glucose-6-phosphate and glycine increase the affinity of PEPC for its
      substrate PEP at pH 8.0 and pH 7.0. Allosteric inhibitors like L-malate and L
      aspartate predominantly decrease the affinity of the carboxylase for PEP at pH
      7.0. This was demonstrated by determination of the enzymatic activity and stopped
      flow (SF) fluorimetry. The binding reaction of PEP to PEPC from Zea mays was
      measured using the fluorescence probe 2-p-toluidinonaphthalene-6-sulfonate (TNS).
      The kinetics are described by an allosteric mechanism with a fast reversible
      bimolecular binding step of PEP to a high affinity (tensed) form of PEPC, which
      is in equilibrium with its low affinity (relaxed) form. The influence of
      allosteric effectors on the conformational transition step is demonstrated in
      support of the description of the kinetics of PEPC by applying a concerted
      allosteric mechanism as introduced by Monod, Wyman and Changeux. In summary, we
      present data for the influence of allosteric activators on the kinetics of PEP
      binding to PEPC and on the concentration dependence of the isomerisation reaction
      between two allosteric forms of PEPC.

PMID- 11527580
TI  - DSC studies of Fusarium solani pisi cutinase: consequences for stability in the
      presence of surfactants.
AB  - The application of cutinase from Fusarium solani pisi as a fat-stain removing
      ingredient in laundry washing is hampered by its lack of stability in the
      presence of anionic surfactants. We postulate that the stability of cutinase
      towards anionics can be improved by mutations increasing its temperature
      stability. Thermal unfolding as measured with DSC, appears to be irreversible,
      though the thermograms are more symmetric than predicted by a simple irreversible
      model. In the presence of taurodeoxycholate (TDOC), the unfolding temperature is
      lower and the unfolding is reversible. We conclude that an early reversible
      unfolding intermediate exists in which a number of additional hydrophobic patches
      are exposed to the solvent, or preferentially are covered with TDOC. Improvement
      of the stability of cutinase with respect to both surfactants and thermal
      denaturation, should thus be directed toward the prevention of exposure of
      hydrophobic patches in the early intermediate.

PMID- 11527581
TI  - Activity coefficients of the peptide and the electrolyte in ternary systems
      water+glycylglycine+NaCl, +NaBr, +KCl and +KBr at 298.2 K.
AB  - The activity coefficients of glycylglycine in four aqueous electrolyte solutions
      (+NaCl, +NaBr, +KCl and +KBr) were obtained at 298.2 K. The mean ionic activity
      coefficient of the electrolyte in aqueous solutions containing the peptide was
      determined from measurements of the potential differences of a cation and an
      anion ion-selective-electrode, each vs. a double junction reference electrode.
      The results show that the nature of the anion has a major effect on the activity
      coefficients of glycylglycine. Comparison of activity coefficient data for
      glycylglycine with literature data for glycine, both in aqueous NaCl solutions,
      indicates that the effect of the electrolyte is larger for the peptide than for
      the amino acid. For the peptide, in all cases, the effect of the electrolyte is
      more important at low molalities of the electrolyte. The Wilson equation was used
      to correlate the activity coefficient data obtained. The correlation results were
      satisfactory for the region of concentrated electrolyte.

PMID- 11527582
TI  - Combined kinetic mechanism describing activation and inhibition of muscle
      glycogen phosphorylase b by adenosine 5'-monophosphate.
AB  - The kinetic analysis of the glycogen chain growth reaction catalyzed by glycogen
      phosphorylase b from rabbit skeletal muscle has been carried out over a wide
      range of concentrations of AMP under the saturation of the enzyme by glycogen.
      The applicability of 23 different variants of the kinetic model involving the
      interaction of AMP and glucose 1-phosphate binding sites in the dimeric enzyme
      molecule is considered. A kinetic model has been proposed which assumes: (i) the
      independent binding of one molecule of glucose 1-phosphate in the catalytic site
      on the one hand, and AMP in both allosteric effector sites and both nucleoside
      inhibitor sites of the dimeric enzyme molecule bound by glycogen on the other
      hand; (ii) the binding of AMP in one of the allosteric effector sites results in
      an increase in the affinity of other allosteric effector site to AMP; (iii) the
      independent binding of AMP to the nucleoside inhibitor sites of the dimeric
      enzyme molecule; (iv) the exclusive binding of the second molecule of glucose 1
      phosphate in the catalytic site of glycogen phosphorylase b containing two
      molecules of AMP occupying both allosteric effector sites; and (v) the catalytic
      act occurs exclusively in the complex of the enzyme with glycogen, two molecules
      of AMP occupying both allosteric effector sites, and two molecules of glucose 1
      phosphate occupying both catalytic sites.

PMID- 11527583
TI  - The role of facilitated diffusion in oxygen transport by cell-free hemoglobins:
      implications for the design of hemoglobin-based oxygen carriers.
AB  - We compared rates of oxygen transport in an in vitro capillary system using red
      blood cells (RBCs) and cell-free hemoglobins. The axial PO(2) drop down the
      capillary was calculated using finite-element analysis. RBCs, unmodified
      hemoglobin (HbA(0)), cross-linked hemoglobin (alpha alpha-Hb) and hemoglobin
      conjugated to polyethylene-glycol (PEG-Hb) were evaluated. According to their
      fractional saturation curves, PEG-Hb showed the least desaturation down the
      capillary, which most closely matched the RBCs; HbA(0) and alpha alpha-Hb showed
      much greater desaturation. A lumped diffusion parameter, K*, was calculated based
      on the Fick diffusion equation with a term for facilitated diffusion. The overall
      rates of oxygen transfer are consistent with hemoglobin diffusion rates according
      to the Stokes-Einstein Law and with previously measured blood pressure responses
      in rats. This study provides a conceptual framework for the design of a 'blood
      substitute' based on mimicking O(2) transport by RBCs to prevent autoregulatory
      changes in blood flow and pressure.

PMID- 11527584
TI  - Protection of radiation-induced protein damage by curcumin.
AB  - Free radical reactions of lysozyme (Lz), tryptophan and disulfides were studied
      with curcumin, a lipid-soluble antioxidant from turmeric, in aqueous solution
      using a pulse radiolysis technique. The binding of curcumin with lysozyme was
      confirmed using absorption, fluorescence and stopped-flow techniques. The free
      radicals of curcumin generated after repairing radicals of disulfides, lysozyme
      and tryptophan absorb at 500-510 nm. Implication of this in evaluating the
      antioxidant behavior of curcumin in protecting proteins is discussed.

PMID- 11527585
TI  - NCD activation of tubulin polymerization.
AB  - Tubulin dimer (tT) was purified from turkey erythrocytes. The motor domain of
      Drosophila non-claret disjunctional protein, NCD(335-700), was expressed in E.
      coli and purified. At 37 degrees C in the presence of GTP, the rate of
      polymerization of tT to microtubule (tMt) is accelerated over threefold by the
      presence of NCD(335-700). At 10 degrees C, the rate of tT polymerization is
      increased from zero, within experimental error, in the absence of NCD(335-700) to
      rates near those observed at 37 degrees C when NCD(335-700) is present. The
      NCD(335-700) concentration dependence of the rate indicated the reactive species
      was NCD(335-700)(n).tT, with n approximately 2. At 10 degrees C in the absence of
      GTP, polymerization does not occur, but tT activates NCD(335-700) MgATPase
      activity 10-fold. For the same conditions, using mians-NCD(335-700), which is
      modified with 2-(4'-maleimidylanilino) naphthalene-6-sulfonic acid, the apparent
      K(D) for binding to tT is 2.3 x 10(-5) M in the presence of MgADP. Replacing ADP
      with AMPPNP or ATP has a negligible effect on K(D). Mians-NCD(335-700) binding to
      tMt is 10-fold stronger than to tT. The above data indicate NCD(335-700) binds at
      a functional site on tT. The stoichiometry is consistent with the formation of
      NCD(335-700)(2).tT which in vitro accelerates self-assembly initiation and/or
      polymerization by binding a second tT in a position favorable for tubulin-tubulin
      interaction. The data suggest that in vivo functional NCD binding to microtubule
      involves one motor domain binding to alpha- and beta-subunits at the interface of
      two different tubulin dimers in a protofilament.

PMID- 11527586
TI  - Adsorption of an amphiphilic penicillin onto human serum albumin:
      characterisation of the complex.
AB  - The complex formed by the interaction of the amphiphilic penicillin drug
      nafcillin and human serum albumin (HSA) in water at 25 degrees C has been
      characterised using a range of physicochemical techniques. Measurements of the
      solution conductivity and the electrophoretic mobility of the complexes have
      shown an ionic adsorption of the drug on the protein surface leading to a surface
      saturation at a nafcillin concentration of 0.012 mmol kg(-1) and subsequent
      formation of drug micelles in solutions of higher nafcillin concentration.
      Measurements of the size of the complex and the thickness of the adsorbed layer
      by static and dynamic light scattering have shown a gradual change in
      hydrodynamic radius of the complex with increasing drug concentration typical of
      a saturation rather than a denaturation process, the magnitude of the change
      being insufficient to account for any appreciable extension or unfolding of the
      HSA molecule. The interaction potential between the HSA/nafcillin complexes, and
      the stability of the complexes were determined from the dependence of diffusion
      coefficients on protein concentration by application of the DLVO colloidal
      stability theory. The results indicate decreasing stability of the colloidal
      dispersion of the drug/protein complexes with an increase in the concentration of
      added drug.

PMID- 11527587
TI  - Prenatal diagnosis of cleft palate by three-dimensional ultrasound.
AB  - Prenatal diagnosis of cleft palate is very important to prenatal consultation and
      management after birth. To examine if three-dimensional (3-D) ultrasound (US) is
      an accurate diagnostic method for clinical use, we analyzed our experience in
      detecting cleft palate by 3-D US. From June 1996 to January 2000, 21 fetuses with
      facial clefts were scanned by 2-D US, as well as by 3-D US. The coronal and
      oblique planes were reconstructed by 3-D US to detect the cleft palate. In
      addition, level II US was performed to find any possibly associated anomalies.
      All the scans were recorded on optic disks for final analysis. In our study, the
      gestational age when prenatal diagnosis was made by US initially was between 20
      and 34 weeks. The accuracy for prenatal diagnosis of cleft lip with or without
      cleft palate by 3-D US was 100%, which was superior to that by 2-D US (p < 0.05).
      In addition, we proposed a novel method to evaluate the cleft palate systemically
      by 3-D US. In conclusion, from our study, fetuses with cleft lip combined with or
      without cleft palate can be easily differentiated by 3-D US. The reconstruction
      of coronal and oblique planes by 3-D US is a powerful tool for detecting cleft
      palate.

PMID- 11527588
TI  - Three-dimensional ultrasound-guided core needle breast biopsy.
AB  - A new core needle breast biopsy system guided by 3-D ultrasound (US) is proposed.
      Our device provides rapid imaging and real-time guidance, as well as breast
      stabilization and a needle guidance apparatus using 3-D imaging. The targeting
      accuracy of our device was tested by inserting a 14-gauge biopsy needle into agar
      phantoms under 3-D US guidance. A total of 18 0.8-mm stainless-steel beads
      embedded in the phantoms defined each of the four target positions tested.
      Positioning accuracy was calculated by comparing needle tip position to the
      preinsertion bead position, as measured by three observers three times each on 3
      D US. The interobserver standard error of measurement was no more than 0.14 mm
      for the beads and 0.27 mm for the needle tips. A 3-D principal component analysis
      was performed to obtain the population distribution of needle tip position
      relative to the target beads for the four target positions. The 3-D 95%
      confidence intervals were found to have total widths ranging from 0.43 to 1.71
      mm, depending on direction and bead position.

PMID- 11527589
TI  - Noninvasive assessment of laryngeal phonation function using color Doppler
      ultrasound imaging.
AB  - Color Doppler imaging (CDI) was used to identify the morphology of vocal folds
      (VF) and to quantify the tissue horizontal displacement velocity (HDV) in the
      vibrating portion of VF. Mucosal HDV that gives an estimate of the stiffness of
      the VF cover is very important clinically. The VF and its cover were shown to be
      very hypoechoic and not adequately visible in B-scan image. However, in this
      study, we found that the structure of the true VF, especially the mucosa and the
      superficial layer of the lamina propria, the so-called "cover," can be easily
      identified and evaluated using CDI. The mean VF displacement velocity was
      measured by decoding the pseudocolor codes of the ultrasound (US) image at the
      vibrating sites. The mucosal mean HDV obtained from 10 normal men of age 34 +/- 8
      years phonating at their most comfortable pitch and intensity (98 +/- 12 Hz, 55
      65 dB) was about 68 +/- 10 cm/s, which agreed reasonably with the literature.
      Therefore, the CDI could be used as a potential tool for assessing the phonation
      function in the larynx nonintrusively.

PMID- 11527590
TI  - An objective method for grading ultrasound images of carotid artery plaques.
AB  - Plaque composition may improve identification of patients at risk of stroke. A
      new method of grading ultrasound (US) images to assess plaque composition is
      described. B-mode US images were obtained from 50 carotid specimens. Image
      analysis parameters were entered into a discriminant analysis package and
      compared retrospectively with histology. Discriminant functions were derived and
      then applied prospectively to image-analysis data obtained from a further 50
      plaque specimens. For the prospective analysis, US images were graded according
      to the relative contribution of calcium, fibrous tissue, haemorrhage and lipid.
      The accuracy for retrospective classification of calcium was 100%, for fibrous
      tissue 97%, for lipid 76% and 68% for haemorrhage (kappa = 0.81). Prospective
      classification showed an overall agreement of 65% (kappa = 0.47). Significant
      intraplaque haemorrhage was identified with an 81% sensitivity and 83%
      specificity. The US method described demonstrated improved accuracy compared to
      previous studies. Further study is required to establish the use of this method
      for in vivo images and its correlation with patient symptoms.

PMID- 11527591
TI  - In vivo ultrasonic measurement of tissue vibration at a stenosis: a case study.
AB  - It is known that bruits often can be heard downstream from stenoses. They are
      thought to be produced by disturbed blood flow and vessel wall vibrations. Our
      understanding of bruits has been limited, though, to analysis of sounds heard at
      the level of the skin. For direct measurements from the stenosis site, we
      developed an ultrasonic pulse-echo multigate system using quadrature phase
      demodulation. The system simultaneously measures tissue displacements and blood
      velocities at multiple depths. This paper presents a case study of a severe
      stenosis in a human infrainguinal vein bypass graft. During systole, nearly
      sinusoidal vessel wall vibrations were detected. Solid tissue vibration
      amplitudes measured up to 2 microm, with temporal durations of 100 ms and
      frequencies of roughly 145 Hz and its harmonics. Cross-axial oscillations were
      also found in the lumen that correlate with the wall vibrations, suggesting
      coupling between wall vibration and blood velocity oscillation.

PMID- 11527592
TI  - Evaluation of blood flow in the cerebral microcirculation: analysis of the refill
      kinetics during ultrasound contrast agent infusion.
AB  - By means of harmonic imaging, it is possible to display brain perfusion
      qualitatively using ultrasound (US) contrast agent (UCA) bolus injection. With
      UCA continuous infusion reaching a steady state, mean microbubble velocity can be
      measured, analyzing the reappearance rate after microbubble destruction by US
      (refill kinetics). We performed an animal pilot study to investigate this new
      method for the assessment of brain perfusion. Using harmonic grey-scale imaging,
      five sedated male beagle dogs were investigated through the intact skull with
      increasing pulsing intervals (250 to 8000 ms) and three UCA infusion rates (0.5,
      1.0 and 1.5 mL/min of Optison). Cerebral blood flow was increased by
      acetazolamide (30 mg/kg BW). Intensity vs. pulsing interval curves were analyzed
      using an exponential curve fit [I(t) = A(1-e(-beta t))] and parameters of the
      curve were compared. We found that increasing the pulsing interval above 4000 ms
      led to no further increase of echo enhancement for infusion rates. Mean beta
      values were not influenced by infusion rate (p = 0.25 and p = 0.55). Mean F
      values increased nonsignificantly with rising infusion rate (p = 0.25 and p =
      0.86). Acetazolamide led to an increase of mean beta and F values (p = 0.18 and p
      = 0.025, respectively). It is possible to evaluate changes in brain perfusion
      through the intact skull by analyzing the UCA refill kinetics after US-induced
      microbubble destruction.

PMID- 11527593
TI  - Automated embolus identification using a rule-based expert system.
AB  - Transcranial Doppler ultrasound (US) can be used to detect microemboli in the
      cerebral circulation, but is still limited because it usually relies on "human
      experts" (HEs) to identify signals corresponding to embolic events. The purpose
      of this study was to develop an automatic system that could replace the HE and,
      thus, make the technique more widely applicable and, potentially, more reliable.
      An expert system, based around a digital signal-processing board, analysed
      Doppler signal patterns in both the time domain and frequency domain. The system
      was trained and tested on Doppler signals recorded during the dissection and
      recovery phases of carotid endarterectomy. It was tested with 74 separate 2.5-min
      recordings that contained at least 575 artefacts in addition to 253 s of
      diathermy interference. The results were compared with the results obtained by
      three HEs. Using a "gold-standard" that classified any event detected by the
      majority of HEs as an embolus, the automatic system displayed a sensitivity of
      94.7% and a specificity of 95.1% for 1151 candidate events 7 dB or more above the
      clutter (signal-to-clutter ratio, SCR, > or = 7 dB), and 89.6% and 95.3%,
      respectively, for 2098 candidate events with SCR > or = 5 dB. The system had a
      very similar performance to individual HEs for SCR > or = 7dB, and was only
      marginally worse for SCR > or = 5 dB.

PMID- 11527594
TI  - Ultrasonic tissue characterization can predict beta-blocker efficacy in dilated
      cardiomyopathy.
AB  - The aim was to determine if the combination of cyclic variation of myocardial
      integrated backscatter (variation IB) and left ventricular mass measurements can
      predict the efficacy of beta-blocker treatment in dilated cardiomyopathy. In 32
      patients, left ventricular mass and variation IB were measured at baseline and
      during 6 microg/kg/min dobutamine infusion before the initiation of beta-blocker
      therapy. Variation IB was measured at left and right ventricular halves in the
      ventricular septum. The baseline left ventricular mass index and transseptal
      variation IB gradient during dobutamine were significantly greater in the
      effective group (1.16 +/- 0.18 g/mL and 1.8 +/- 0.6 dB) than in the ineffective
      group (0.94 +/- 0.28 g/mL, p = 0.032 and 0.4 +/- 0.6 dB, p < 0.005). When both
      baseline left ventricular mass index > or = 1.05 g/mL and transseptal variation
      IB gradient during dobutamine > or = 1.5 dB were defined as predictive criteria
      for the effective group, the sensitivity was 78% and the specificity was 86%.
      Analysis of transseptal variation IB during dobutamine may provide useful
      information predicting the efficacy of beta-blocker therapy in dilated
      cardiomyopathy.

PMID- 11527595
TI  - Can natural strain and strain rate quantify regional myocardial deformation? A
      study in healthy subjects.
AB  - Strain rate (SR) and strain (epsilon) have been proposed as new ultrasound (US)
      indices for quantifying regional wall deformation, and can be measured from color
      Doppler myocardial data by determining the local spatial velocity gradient. The
      aim of this study was to define normal regional SR/epsilon values for both radial
      and longitudinal myocardial deformation. SR/epsilon profiles were obtained from
      40 healthy volunteers. For radial deformation, posterior left ventricular (LV)
      wall SR/epsilon were calculated. For longitudinal, they were determined for
      basal, mid- and apical segments of the 1. septum; 2. lateral, 3. posterior and 4.
      anterior LV walls and for the 5. right ventricular (RV) lateral wall. SR/epsilon
      values describing radial deformation were higher than the corresponding
      SR/epsilon values obtained for longitudinal deformation. Longitudinal SR/epsilon
      were homogeneous throughout the septum and all LV walls. This was in contrast to
      the normal base-apex velocity gradient. The RV segmental SR/epsilon values were
      higher than those obtained from the corresponding LV wall and inhomogeneous
      (higher in the apical segments). SR/epsilon imaging appears to be a robust
      technique for quantifying regional myocardial deformation.

PMID- 11527596
TI  - Pathological changes in human malignant carcinoma treated with high-intensity
      focused ultrasound.
AB  - The purpose of this study was to investigate the pathologic changes of
      extracorporeal ablation of human malignant tumors with high-intensity focused
      ultrasound (HIFU). HIFU treatment was performed in the 164 patients with liver
      cancer, breast cancer, malignant bone tumor, soft tissue sarcoma and other
      malignant tumors at focal peak intensities from 5000 W x cm(-2) to 20,000 W x cm(
      2), with operating frequencies of 0.8 to 3.2 MHz. To explore the pathologic
      impact of extracorporeal HIFU, 30 patients with malignant carcinoma underwent
      surgical removal after HIFU treatment. Pathologic findings showed that the
      treated tissues demonstrated homogeneous coagulative necrosis with an
      irreversible tumor cell death and severe damage to tumor blood vessels at the
      level of microsvasculature within the HIFU-targeted region. Thermolesions to
      intervening tissue were never observed. The treated region had a sharp border
      comprising only several cell layers between the treated and untreated areas. The
      repair of lesions had the processes of necrotic tissue absorption and granulation
      tissue replacement. It is concluded that extracorporeal treatment of human solid
      malignancies with HIFU could be safe, effective and feasible. As a noninvasive
      therapy, HIFU would be used clinically to treat patients with solid malignancies.

PMID- 11527597
TI  - Lysis and sonoporation of epidermoid and phagocytic monolayer cells by diagnostic
      ultrasound activation of contrast agent gas bodies.
AB  - Epidermoid A431 (human carcinoma) and phagocytic RAW-264.7 cells were grown as
      monolayers on 5-microm thick Mylar sheets by standard culture methods. The sheets
      formed one window of disk-shaped ultrasound (US) exposure chambers. A diagnostic
      US machine in spectral Doppler mode was used for exposure with a 3.5-MHz scanhead
      aimed upward at the chamber in a 37 degrees C water bath. Sonoporation and cell
      lysis were evaluated for assessment of cell membrane damage. For both epidermoid
      and RAW cells on the upper window with 1% Optison contrast agent, cell lysis was
      detectable in addition to sonoporation. The phagocytic cells tended to retain the
      gas bodies when incubated with contrast agent, and membrane damage occurred even
      for exposure on the bottom window. The effects were also seen for RAW cells
      incubated with 5% contrast agent for 15 min and then rinsed before exposure.
      Above a threshold range for lysis and sonoporation of 0.09 to 0.23 MPa, the
      counts of affected cells increased for both cell lines to about 20% at 0.83 MPa.
      These results indicate relatively low thresholds for membrane damage induced by
      diagnostic US activation of contrast agent gas bodies, with a potential for
      targeting of these effects to phagocytic cells.

PMID- 11527598
TI  - Contrast-transfer efficiency for continuously varying tissue moduli: simulation
      and phantom validation.
AB  - This study consisted of two parts. In the first part, the contrast-transfer
      efficiency (CTE) in elastography was extended to account for continuous changes
      of modulus distribution. It was shown that, for a finite size background, the
      strain contrast approaches the modulus contrast in the case of Gaussian
      distributions. Thus, an increase in the CTE was obtained. For a fixed background
      size, it was shown that the CTE increases as the SD of the Gaussian distribution
      increases. This property was explained by the redistribution of strain
      concentrations at the inclusion/background interface. In the second part of the
      study, the CTE was verified experimentally. Six gelatin/agar/water-based phantoms
      embedding inclusions with modulus contrast varying between +/- 6 dB were
      manufactured. It was shown that the modulus at the interface inclusion/background
      was continuous and, in turn, resulted in an increase of the CTE as compared to
      the known case of a sharp boundary. The continuous inclusion/background interface
      was explained by the existence of an osmotic pressure gradient.

PMID- 11527599
TI  - Ultrasonic power balances--effect of a coupling window on the power measured from
      physiotherapy ultrasound units.
AB  - The output from physiotherapy ultrasound (US) probes is usually measured using a
      radiation force balance. Some balances are sealed and incorporate a membrane
      coupling window. The probes are highly resonant, and the output may be affected
      by changes in acoustic loading caused by the membrane. A model has been developed
      to examine this effect, and predicts that a polythene membrane 100-microm thick
      can change the output power by up to 17%.

PMID- 11527600
TI  - Ultrasound-guided reduction of an incarcerated Spigelian hernia.
AB  - Spigelian hernia is a rare abdominal hernia. We report a case in which its
      diagnosis proved ultrasonography to be an effective tool, not only to diagnose an
      incarcerated Spigelian hernia but, moreover, to reduce it by echo-probe
      palpation. Ultrasound (US) is an aid for therapy of various diseases. In our
      experience, US-guidance prevented possible damage related to forced and wrongly
      applied compression during the hernia reduction, and allowed us to perform
      surgical repair on an elective basis. In conclusion, if an incarcerated Spigelian
      hernia is suspected, a US examination should be done on an emergency basis to
      confirm the diagnosis and to attempt US-guided reduction.

PMID- 11527601
TI  - Estimation of antithyroid drug dose in Graves' disease: value of quantification
      of thyroid blood flow with color duplex sonography.
AB  - The purpose of this study was to evaluate if there is an association between the
      antithyroid drug dose that is needed to establish euthyroidism and thyroid blood
      flow measurements. A total of 23 Graves' disease patients with euthyroidism
      taking antithyroid drug therapy were enlisted to undergo spectral duplex
      sonography of the thyroid arteries and color-flow mapping of the thyroid gland.
      Color pixel density (CPD) was calculated with computer assistance from the color
      flow maps. There was a strong correlation between the CPD and methimazole dose
      (rp = 0.79). Methimazole maintenance dosage could be predicted from CPD values
      with a coefficient of determination of 0.62. In conclusion, CPD measurements
      could be a useful tool for the clinical endocrinologist to estimate the
      antithyroid drug dose that is needed to maintain euthyroidism.

PMID- 11527602
TI  - Infant cerebral ventricle volume: a comparison of 3-D ultrasound and magnetic
      resonance imaging.
AB  - Enlargement of the cerebral lateral ventricles is observed in several
      neuropsychiatric disorders with origins in early brain development. Lateral
      ventricle size is also predictive of poor neurodevelopmental outcome in premature
      infants. Three-dimensional (3-D) ultrasound (US) offers an improved methodology
      for the study of lateral ventricle volume in neonates and infants. To assess the
      validity of ventricle volume measures obtained with 3-D US, we compared the
      volumes obtained by 3-D US with magnetic resonance imaging (MRI) in seven
      infants. Ventricle volumes were determined using a computer-assisted image
      analysis program, IRIS. There was excellent correlation between ventricle volumes
      obtained with 3-D US and those obtained with MRI (intraclass correlation
      coefficient 0.92, F = 23.28, p = 0.00027), indicating that 3-D US provides valid
      measures of overall lateral ventricle volume compared to the "gold standard" of
      MRI. 3-D US can provide an economical and practical means of studying lateral
      ventricle volume in neonates, a neurostructural marker of abnormal brain
      development.

PMID- 11527603
TI  - Ultrasound-induced physiological effects and secondary metabolite (saponin)
      production in Panax ginseng cell cultures.
AB  - This work was aimed at the effects of ultrasound (US) on the growth and secondary
      metabolite biosynthesis of cultured plant cells. Suspension cultures of Panax
      ginseng cells were exposed to US at power density below 82 mW/cm3 for short
      periods of time (1-4 min) in a US bath (38.5-kHz fixed frequency and 810 W
      maximum peak power). Under most exposure conditions, US stimulated the
      biosynthesis of secondary metabolites, the ginsenoside saponins of ginseng cells,
      increasing the total saponin content of the cell by up to 75%. The growth and
      viability of ginseng cells were usually depressed immediately after the exposure
      to US, but recovered gradually to levels similar to those of a normal culture in
      a few days, with virtually no net loss of biomass yield at the end of the culture
      period. At some lower US doses, sonicated cultures could even reach slightly
      higher biomass yields than that of normal cultures. The effects of US on cell
      growth and secondary metabolite yield showed a significant correlation with the
      total US energy emitted (i.e., the product of US power and exposure time).
      Mechanical stress and microstreaming induced by acoustic cavitation were
      considered as the most possible causes of the various physiological effects of US
      on ginseng cells. In particular, the stimulation of secondary metabolite
      production by US may be a result of US-induced plant cell defense response.

PMID- 11527605
TI  - Quality of cardiovascular care in the US.

PMID- 11527606
TI  - Patent foramen ovale: a review of associated conditions and the impact of
      physiological size.
AB  - Patent foramen ovale (PFO) is implicated in platypnea-orthodeoxia, stroke and
      decompression sickness (DCS) in divers and astronauts. However, PFO size in
      relation to clinical illness is largely unknown since few studies evaluate PFO,
      either functionally or anatomically. The autopsy incidence of PFO is
      approximately 27% and 6% for a large defect (0.6 cm to 1.0 cm). A PFO is often
      associated with atrial septal aneurysm and Chiari network, although these
      anatomic variations are uncommon. Methodologies for diagnosis and anatomic and
      functional sizing of a PFO include transthoracic echocardiography (TTE),
      transesophageal echocardiography (TEE) and transcranial Doppler (TCD), with
      saline contrast. Saline injection via the right femoral vein appears to have a
      higher diagnostic yield for PFO than via the right antecubital vein. Saline
      contrast with TTE using native tissue harmonics or transmitral pulsed wave
      Doppler have quantitated PFO functional size, while TEE is presently the
      reference standard. The platypnea-orthodeoxia syndrome is associated with a large
      resting PFO shunt. Transthoracic echocardiography, TEE and TCD have been used in
      an attempt to quantitate PFO in patients with cryptogenic stroke. The larger PFOs
      (approximately > or =4 mm size) or those with significant resting shunts appear
      to be clinically significant. Approximately two-thirds of divers with unexplained
      DCS have a PFO that may be responsible and may be related to PFO size. Limited
      data are available on the incidence of PFO in high altitude aviators with DCS,
      but there appears to be a relationship. A large decompression stress is
      associated with extra vehicular activity (EVA) from spacecraft. After four cases
      of serious DCS in EVA simulations, a resting PFO was detected by contrast TTE in
      three cases. Patent foramen ovales vary in both anatomical and functional size,
      and the clinical impact of a particular PFO in various situations (platypnea
      orthodeoxia, thromboembolism, DCS in underwater divers, DCS in high-altitude
      aviators and astronauts) may be different.

PMID- 11527607
TI  - Does the presence of thrombus seen on a coronary angiogram affect the outcome
      after percutaneous coronary angioplasty? An Angiographic Trials Pool data
      experience.
AB  - OBJECTIVES: This study aimed to determine whether pre-existing angiographic
      thrombus was associated with adverse in-hospital and six-month outcomes after
      percutaneous coronary interventions. BACKGROUND: There are conflicting data about
      whether pre-existing thrombus is an independent predictor of adverse in-hospital
      and short-term outcome after coronary interventions. METHODS: The Angiographic
      Trials Pool, a data set derived from eight prospective randomized trials, was
      analyzed. The study population consisted of 7,917 patients who underwent coronary
      interventions between 1986 and 1995. Two trials were excluded because they did
      not collect information regarding thrombus. Patients from the other six trials
      were divided on the basis of the presence or absence of thrombus. RESULTS: In
      patients with (n = 2,752) and without (5,165) thrombus, in-hospital mortality
      following angioplasty was low (0.8 vs. 0.6%, p = 0.207). Several adverse outcomes
      were higher in patients with thrombus: death/myocardial infarction (8.4 vs. 5.5%,
      p < or = 0.001), in-hospital abrupt closure (5.9 vs. 3.9%, p < or = 0.001) and an
      in-hospital composite of death, myocardial infarction and/or repeat
      revascularization (15.4 vs. 11.2%, p < or = 0.001). Six-month mortality was low
      and comparable between the two groups (2.1 vs. 1.8%, p = 0.34), but the incidence
      of six-month death/myocardial infarction was higher in patients with thrombus
      (11.7 vs. 8.7%, p < or = 0.0001). CONCLUSIONS: Percutaneous coronary angioplasty
      can be performed with low mortality in patients with pre-existing thrombus,
      although these patients are at higher risk of in-hospital and six-month
      death/myocardial infarction. Continued efforts are required to optimize the
      outcome in these high risk patients.

PMID- 11527608
TI  - Treatment of diffuse in-stent restenosis with rotational atherectomy followed by
      radiation therapy with a rhenium-188-mercaptoacetyltriglycine-filled balloon.
AB  - OBJECTIVES: This study was done to evaluate the feasibility and efficacy of beta
      radiation therapy with a rhenium-188-mercaptoacetyltriglycine ((188)Re-MAG(3))
      filled balloon after rotational atherectomy for diffuse in-stent restenosis
      (ISR). BACKGROUND: Rotational atherectomy has been shown to be safe and efficient
      for the treatment of ISR, but the recurrence rate is still high. Intracoronary
      beta-irradiation after rotational atherectomy may be a reasonable approach to
      prevent recurrent ISR. METHODS: Fifty consecutive patients with diffuse ISR
      (length >10 mm) in native coronary arteries underwent rotational atherectomy and
      adjunctive balloon angioplasty, followed by beta-irradiation using a (188)Re
      MAG(3)-filled balloon catheter. The radiation dose was 15 Gy at a depth of 1.0 mm
      into the vessel wall. RESULTS: The mean lengths of the lesion and irradiated
      segment were 25.6 +/- 12.7 mm and 37.6 +/- 11.2 mm, respectively. Radiation was
      delivered successfully to all patients, with a mean irradiation time of 201.8 +/-
      61.7 s. No adverse event, including myocardial infarction, death or stent
      thrombosis, occurred during the follow-up period (mean 10.3 +/- 3.7 months), and
      nontarget vessel revascularization was needed in one patient. The six-month
      binary angiographic restenosis rate was 10.4%, and the loss index was 0.17 +/-
      0.31. CONCLUSIONS: Beta-irradiation using a (188)Re-MAG(3)-filled balloon after
      rotational atherectomy is safe and feasible in patients with diffuse ISR, and it
      may improve their clinical and angiographic outcomes. Further prospective,
      randomized trials are warranted to evaluate the synergistic effect of debulking
      and irradiation in patients with diffuse ISR.

PMID- 11527609
TI  - Vascular complications after percutaneous coronary interventions following
      hemostasis with manual compression versus arteriotomy closure devices.
AB  - OBJECTIVES: We evaluated the vascular complications after hemostasis with
      arteriotomy closure devices (ACD) versus manual compression after percutaneous
      coronary interventions (PCI). BACKGROUND: Previous clinical studies have
      indicated that ACD can be used for achievement of hemostasis and early ambulation
      after PCI. This study investigated the safety of ACD in achieving hemostasis
      after PCI compared with manual compression in a large cohort of consecutive
      patients. METHODS: A total of 5,093 patients were followed after PCI was
      performed with the transfemoral approach. Univariate and multivariate analysis
      were used to identify the predictors of vascular complications with ACD (n = 516)
      or with manual compression (n = 5,892) as a hemostasis option after sheath
      removal. RESULTS: The use of ACD was associated with a more frequent occurrence
      of hematoma compared with manual compression (9.3 vs. 5.1%, p < 0.001). There was
      also a higher rate of significant hematocrit drop (>15%) with ACD versus manual
      compression (5.2% vs. 2.5%, p < 0.001). Similar rates of pseudoaneurysm and
      arteriovenous fistulae were noted with either hemostasis technique. Vascular
      surgical repair at the access site was required more often with ACD versus manual
      compression (2.5 vs. 1.5%, p = 0.03). CONCLUSIONS: In this early experience with
      ACD after PCI, their use was associated with higher vascular complication rates
      than hemostasis with manual compression.

PMID- 11527610
TI  - Arteriotomy closure devices-the FDA perspective.

PMID- 11527611
TI  - Clinical and quantitative coronary angiographic predictors of coronary
      restenosis: a comparative analysis from the balloon-to-stent era.
AB  - OBJECTIVES: We sought to assess whether coronary stents have modified the
      predictive value of demographic, clinical and quantitative coronary angiographic
      (QCA) predictors of coronary restenosis. BACKGROUND: A systematic analysis in a
      large cohort of registries and randomized trials of the percutaneous transluminal
      coronary angioplasty (PTCA) and stent era has never been performed. METHODS: A
      total of 9,120 treated lesions in 8,156 patients included in nine randomized
      trials and 10 registries, with baseline, post-procedural and six-month follow-up
      QCA analyses, were included in this study. Predictors of restenosis were
      identified with univariate and multivariate logistic regression analyses.
      Interaction terms were introduced in the regression equation to evaluate whether
      the predictors of restenosis were common to both eras or specific for either one
      of the revascularization techniques. RESULTS: The restenosis rate was 35% after
      PTCA and 19% after angioplasty with additional stenting. In the univariate
      analysis, favorable predictors were previous coronary artery bypass graft surgery
      (CABG), stent use, stent length and a large pre-procedural minimal lumen diameter
      (pre-MLD); unfavorable predictors were weight, body mass index, diabetes
      mellitus, multi-vessel disease, lesion length and a high residual post-procedural
      diameter stenosis (post-DS). Predictors specific for the PTCA population were a
      large post-procedural MLD (post-MLD) as favorable and a severe pre-procedural DS
      (pre-DS) as unfavorable. Favorable predictors specific for the stent population
      were a large post-MLD and a large pre-procedural reference diameter (pre-RD). In
      the multivariate analysis, the best model included the following favorable
      predictors: stent use, a large post-MLD, previous CABG and the interaction term
      between stent use and a large post-MLD; unfavorable predictors were lesion length
      and diabetes mellitus. CONCLUSIONS: There are no major differences in demographic
      and clinical predictors of coronary restenosis between PTCA and stent
      populations. In the modern (stent) era, a severe pre-DS is no longer an
      unfavorable predictor of restenosis. Still important, but more so in the stent
      population, is a large post-MLD (optimal result). Finally, a larger pre-RD became
      a favorable predictor with the advent of stenting.

PMID- 11527612
TI  - Effect of glycoprotein IIb/IIIa receptor inhibition on angiographic complications
      during percutaneous coronary intervention in the ESPRIT trial.
AB  - OBJECTIVES: We sought to determine whether eptifibatide decreases the incidence
      of in-laboratory angiographic complications and to determine the relationship of
      angiographically evident complications to elevations of creatine kinase-MB (CK
      MB) enzyme levels during percutaneous coronary intervention. BACKGROUND: In the
      Enhanced Suppression of the Platelet IIb/IIIa Receptor with Integrilin Therapy
      (ESPRIT) trial, eptifibatide during coronary intervention was associated with
      decreased ischemic complications at 48 h and 30 days. METHODS: Patients (n =
      2,064) were randomized to placebo versus eptifibatide (two 180 microg/kg boluses
      10 min apart and as a continuous infusion of 2 microg/kg per min) during
      percutaneous coronary stenting. Angiographic complications including major
      dissection, distal embolization, residual thrombus, abrupt closure, residual
      stenosis >50% and side-branch occlusion were prospectively recorded by the
      operator. Creatine kinase-MB levels were measured after the procedure and every 6
      h thereafter. The incidence of angiographic complications and CK-MB elevation was
      determined for eptifibatide versus placebo groups. RESULTS: Eptifibatide-treated
      patients demonstrated nonsignificant trends toward fewer angiographic
      complications (10 vs. 12% for placebo patients, p = 0.13) and, for patients with
      angiographic complications, fewer subsequent CK-MB elevations (43 vs. 50% for
      placebo patients, p = 0.31). In patients without any angiographic complications,
      the incidence of CK-MB elevation >3 times the normal was 7% with placebo and 4%
      with eptifibatide (p = 0.003). CONCLUSIONS: Eptifibatide during nonurgent
      coronary stent intervention only minimally (and insignificantly) reduces the
      incidence of angiographic complications and subsequent CK-MB elevations in
      patients developing an angiographic complication. The greater effect is to reduce
      myocardial infarction in patients undergoing otherwise uneventful coronary stent
      implantation as well as in the overall study population.

PMID- 11527613
TI  - Long-term clinical outcome and predictors of major adverse cardiac events after
      percutaneous interventions on saphenous vein grafts.
AB  - OBJECTIVES: The purpose of this study was to examine the long-term clinical
      outcome after percutaneous intervention of saphenous vein grafts (SVG) and to
      identify the predictors of major adverse cardiac events (MACE). BACKGROUND:
      Percutaneous interventions of SVGs have been associated with more procedural
      complications and higher restenosis rates compared with interventions on native
      vessels. METHODS: From 1993 to 1997, 1,062 patients underwent percutaneous
      intervention on 1,142 SVG lesions. Procedural, in-hospital and long-term clinical
      outcomes were recorded in a database and analyzed. RESULTS: In-hospital MACE
      occurred in 137 patients (13%) including death (8%), Q-wave myocardial infarction
      (MI) (2%) and coronary artery bypass surgery (3%). Late MACE occurred in 565
      patients (54%) including death (9%), Q-wave MI (9%) and target vessel
      revascularization (36%). Any MACE occurred in 457 (43%) patients. Follow-up was
      available in 1,056 (99%) patients at 3 +/- 1 year. Univariate predictors were
      restenotic lesion (odds ratio [OR]: 2.47, confidence interval [CI]: 1.13 to 3.85,
      p = 0.0003), unstable angina (OR: 1.99, CI: 1.27 to 2.91, p = 0.04) and
      congestive heart failure (CHF) (OR: 1.97, CI: 1.14 to 3.24, p = 0.02) for in
      hospital MACE, and peripheral vascular disease (PVD) (OR: 2.18, CI: 1.34 to 3.44,
      p = 0.002), intra-aortic balloon pump placement (OR: 2.08, CI: 1.13 to 3.85, p =
      0.02) and previous MI (OR: 1.97, CI: 1.14 to 3.25, p = 0.007) for late MACE.
      Independent multivariate predictors for late MACE were restenotic lesion
      (relative risk [RR] 1.33, p = 0.02), PVD (RR: 1.31, p = 0.01), CHF (RR: 1.42, p =
      0.01) and multiple stents (RR: 1.47, p = 0.004). Angiographic follow-up was
      available for 422 patients. Angiographic restenosis occurred in 122 (29%) of
      stented SVGs and 181 (43%) of nonstented SVGs (p = 0.04). Stent implantation did
      not confer a survival benefit. CONCLUSIONS: Despite the use of new interventional
      devices, SVG interventions are associated with significant morbidity and
      mortality; SVG stenting is not associated with better three-year event-free
      survival. This may be due to progressive disease at nonstented sites.

PMID- 11527614
TI  - TIMI frame count immediately after primary coronary angioplasty as a predictor of
      functional recovery in patients with TIMI 3 reperfused acute myocardial
      infarction.
AB  - OBJECTIVES: The purpose of this study was to evaluate whether higher coronary
      blood flow, estimated by the corrected Thrombolysis In Myocardial Infarction
      (TIMI) frame count (CTFC), is related to better functional and clinical outcome
      after successful percutaneous transluminal coronary angioplasty (PTCA) in
      patients with acute myocardial infarction (AMI). BACKGROUND: Experimental studies
      have found that functional recovery of the infarcted myocardium was associated
      with increased blood flow (reactive hyperemia) to the infarcted bed shortly after
      reperfusion. METHODS: We measured CTFC immediately after successful (TIMI 3)
      primary PTCA in 104 consecutive patients with their first AMI. Wall motion score
      index (WMSI) and the presence of pericardial effusion were assessed by two
      dimensional echocardiography before and one month after PTCA. RESULTS: The
      patients were divided into two groups according to mean CTFC for corresponding
      coronary artery of the control group: TIMI 3 slow group (45 patients, 40 > CTFC >
      or = 23) and TIMI 3 fast group (59 patients, CTFC < 23). There were no
      significant differences in the baseline characteristics and WMSI before
      reperfusion between the two groups. Improvement of WMSI in the TIMI 3 fast group
      was significantly greater than that of the TIMI 3 slow group (1.33 +/- 0.52 vs.
      0.60 +/- 0.34, p < 0.001). Pericardial effusion and intractable heart failure
      were observed more frequently in the TIMI 3 slow group than in the TIMI 3 fast
      group (27 vs. 10%; p < 0.05, 36 vs. 17%; p < 0.05). Corrected TIMI frame count,
      assessed as a continuous variable, had a significant correlation with the change
      in WMSI (r = 0.60, p < 0.001) after adjusting for age, gender, history of
      hypertension, history of diabetes, elapsed time to PTCA, collateral grade,
      presence of antegrade flow before PTCA and number of diseased vessels.
      CONCLUSIONS: Lower CTFC of the infarct-related artery immediately after PTCA was
      associated with greater functional recovery; and hence, CTFC can predict clinical
      and functional outcome in patients with successful PTCA.

PMID- 11527615
TI  - Cutting balloon angioplasty for the treatment of in-stent restenosis: a matched
      comparison with rotational atherectomy, additional stent implantation and balloon
      angioplasty.
AB  - OBJECTIVES: The purpose of the study was to determine whether cutting balloon
      angioplasty (CBA) has advantages over other modalities in treatment of in-stent
      restenosis (ISR). BACKGROUND: Controversies exist regarding optimal treatment for
      ISR. Recently, CBA emerged as a tool in management of ISR. METHODS: A total of
      648 lesions treated for ISR were divided into four groups according to the
      treatment strategy: CBA, rotational atherectomy (ROTA), additional stenting
      (STENT), and percutaneous transluminal coronary angioplasty (PTCA). Following the
      matching process, 258 lesions were entered into the analysis. RESULTS: Baseline
      clinical and angiographic characteristics were similar among the groups (p = NS).
      Acute lumen gain was significantly higher in the STENT group (2.12 +/- 0.7 mm),
      whereas in the CBA group the gain was similar to one achieved following ROTA and
      following PTCA (1.70 +/- 0.6 vs. 1.79 +/- 0.5 mm and 1.56 +/- 0.7 mm,
      respectively; p = NS). The lumen loss at follow-up was lower for the CBA versus
      ROTA and versus STENT (0.63 +/- 0.6 vs. 1.30 +/- 0.8 mm and 1.36 +/- 0.8 mm,
      respectively; p < 0.0001), yielding a lower recurrent restenosis rate (20% vs.
      35.9% and 41.4%, respectively; p < 0.05). By multivariate analysis, CBA (odds
      ratio [OR] = 0.17; confidence interval [CI], 0.06 to 0.51; p = 0.001) and diffuse
      restenosis type at baseline (OR = 2.07; CI, 1.15 to 3.71; p = 0.02) were
      identified as predictors of target lesion revascularization. CONCLUSIONS: We
      conclude that CBA is a safe and efficient technique for treatment of ISR, with
      immediate results similar to atheroablation and better clinical and angiographic
      outcomes at follow-up. This approach might be implemented as a viable option in
      management of focal ISR and to prepare diffuse ISR for brachytherapy treatment.

PMID- 11527616
TI  - A cutting edge technology, or is it?

PMID- 11527617
TI  - Prevalence of coronary artery disease and its relationship to lipids in a
      selected population in South India: The Chennai Urban Population Study (CUPS No.
      5).
AB  - OBJECTIVES: The aim of this study was to assess the prevalence and risk factors
      for coronary artery disease (CAD) in a native urban South Indian population.
      BACKGROUND: High prevalence rates of premature CAD have been reported in migrant
      Asian Indians. There are very few studies on CAD in native Indians living in the
      Indian subcontinent. METHODS: The Chennai Urban Population Study (CUPS) is an
      epidemiological study involving two residential areas in Chennai in South India.
      Of the total of 1,399 eligible subjects (age > or =20 years), 1,262 (90.2%)
      participated in the study. All the study subjects underwent a glucose tolerance
      test and were categorized as having normal glucose tolerance (NGT), impaired
      glucose tolerance (IGT) or diabetes. Twelve-lead electrocardiogram (ECG) was
      performed in 1,175 individuals (84%). Coronary artery disease was diagnosed based
      on previous medical history or Minnesota coding of ECGs. RESULTS: The overall
      prevalence rate of CAD is 11.0% (age standardized, 9.0%). The prevalence rates of
      CAD were 9.1%, 14.9% and 21.4% in those with NGT, IGT and diabetes, respectively.
      Prevalence of CAD increased with an increase in total cholesterol (trend chi
      square: 26.2, p < 0.001), low-density lipoprotein (LDL) cholesterol (trend chi
      square: 24.5, p < 0.001), triglycerides (trend chi-square: 9.96, p = 0.002) and
      total cholesterol/high-density lipoprotein ratio (trend chi-square: 6.14, p =
      0.0132). Multiple logistic regression analysis identified age (odds ratio [OR]:
      1.05, p < 0.001) and LDL cholesterol (OR: 1.009, p = 0.051) as the risk factors
      for CAD. CONCLUSIONS: The prevalence of CAD is rising rapidly in urban India.
      Lifestyle changes and aggressive control of risk factors are urgently needed to
      reverse this trend.

PMID- 11527618
TI  - Tackling the growing epidemic of cardiovascular disease in South Asia.

PMID- 11527619
TI  - Gender differences and temporal trends in clinical characteristics, stress test
      results and use of invasive procedures in patients undergoing evaluation for
      coronary artery disease.
AB  - OBJECTIVES: This study examined gender differences and temporal changes in the
      clinical characteristics of patients referred for nuclear stress imaging, their
      imaging results and subsequent utilization of coronary angiography and
      revascularization. BACKGROUND: Gender bias may influence resource utilization in
      patients with coronary artery disease (CAD). No study has analyzed gender
      differences and time trends in patients referred for noninvasive testing and
      subsequent use of invasive procedures. METHODS: Between January 1986 and December
      1995, 14,499 patients (5,910 women and 8,589 men) without established CAD
      underwent stress myocardial perfusion imaging. The clinical characteristics,
      imaging results, coronary angiograms and revascularization outcomes were compared
      in women and men over time. RESULTS: The mean pretest probability of CAD was
      lower in women (45%) than in men (70%) (p < 0.001). More women (69%) than men
      (42%) had normal nuclear images (p < 0.001). Men (17%) were more likely than
      women (8%) to undergo coronary angiography (p < 0.001). Male gender was
      independently associated with referral for coronary angiography (multivariate
      model: chi-square = 16, p < 0.001) but was considerably weaker than the imaging
      variables (summed reversibility score: chi-square = 273, p < 0.001).
      Revascularization was performed in more men (46% of the population undergoing
      angiography) than women (39%) (p = 0.01), but gender was not independently
      associated with referral to revascularization. There were no significant
      differences in clinical, imaging or invasive variables between the genders over
      time. CONCLUSIONS: There was little evidence for a bias against women in this
      study. Women were somewhat less likely to undergo coronary angiography but were
      referred for stress perfusion imaging more liberally. Practice patterns remained
      constant over this 10-year period.

PMID- 11527620
TI  - Race and the decision to refer for coronary revascularization: the effect of
      physician awareness of patient ethnicity.
AB  - OBJECTIVES: We sought to assess whether there were differences, relative to
      racial ethnicity, in coronary revascularization recommendations made by a panel
      that had no knowledge of the patients' ethnicity. BACKGROUND: Coronary
      revascularization is employed less frequently in African American than in white
      patients. It is unclear whether this utilization pattern is driven by clinical
      differences between the two populations or by nonclinical factors. METHODS: Data
      were reviewed from 938 (26.5% African American, 73.5% white) consecutive cardiac
      catheterizations done between 1993 and 1995. Revascularization recommendations
      were made by cardiologists and cardiothoracic surgeons provided with the
      patients' clinical and angiographic data, but without knowledge of their
      ethnicity. Revascularization recommendations were compared between African
      American and white patients and correlated with clinical characteristics.
      RESULTS: No difference was noted in the percentage of African American and white
      patients recommended for revascularization, without reference to whether the
      recommendation was for percutaneous transluminal coronary angioplasty (PTCA) or
      for coronary artery bypass graft surgery (CABG) 40 vs. 46%, p = NS). African
      Americans were recommended more frequently for PTCA (22 vs. 18%, p = NS), whereas
      CABG was recommended for more white patients (28 vs. 18%, p = 0.002).
      Significantly fewer African Americans had disease in the left main or left
      anterior descending coronary artery or in multiple arteries. After adjusting for
      age, co-morbidity, left ventricular dysfunction and the extent of coronary
      disease, African Americans were more likely to have a recommendation for PTCA
      (odds ratio [OR] 1.42, 95% confidence interval [CI] 0.96 to 2.11, p = 0.08) and
      less likely to have a recommendation for CABG (OR 0.59, 95% CI 0.37 to 0.94, p =
      0.02). CONCLUSIONS: This study suggests that when only clinical factors are
      considered, the rates of recommendations for revascularization will be similar
      for white and African American patients; but the type of revascularization
      procedure may differ by ethnicity and may depend, in part, on clinical factors.

PMID- 11527621
TI  - Renal insufficiency and cardiovascular events in postmenopausal women with
      coronary heart disease.
AB  - OBJECTIVES: This study sought to determine the independent association of renal
      insufficiency with cardiovascular risk among women with known coronary heart
      disease (CHD). BACKGROUND: Although patients with end-stage renal disease and
      proteinuria are at high risk for cardiovascular events, little is known about the
      cardiovascular risk associated with moderate renal insufficiency. METHODS: The
      Heart and Estrogen/progestin Replacement Study (HERS) was a clinical trial among
      2,763 women with coronary disease who were randomized to conjugated estrogen plus
      progestins or identical placebo and followed for a mean of 4.1 years. Women were
      categorized as having normal renal function (creatinine < 1.2 mg/dl; n = 2,012),
      mild renal insufficiency (1.2 mg/dl to 1.4 mg/dl; n = 567) and moderate renal
      insufficiency (>1.4 mg/dl; n = 182). We examined the independent association of
      renal function with incident cardiovascular events including CHD death, nonfatal
      myocardial infarction, hospitalization for unstable angina, stroke and transient
      ischemic attacks. RESULTS: Compared with women with normal renal function, those
      with mild and moderate renal insufficiency were older, more likely to be black,
      have a history of hypertension and diabetes and have higher serum levels of
      triglycerides and lipoprotein(a). After multivariate adjustment, both mild
      (relative hazards [RH] = 1.24; 95% confidence interval [CI]: 1.0 to 1.5) and
      moderate renal insufficiency (RH = 1.57; 95% CI: 1.2 to 2.1) were independently
      associated with increased risk for cardiovascular events compared with women with
      normal renal function. CONCLUSIONS: Renal insufficiency is an independent risk
      factor for cardiovascular events in postmenopausal women with known coronary
      artery disease. Renal function may add helpful information to CHD risk
      stratification.

PMID- 11527622
TI  - Effects of interleukin-1 gene polymorphisms on the development of coronary artery
      disease associated with Chlamydia pneumoniae infection.
AB  - OBJECTIVES: This study was done to elucidate the effects of interleukin (IL)-1
      gene polymorphisms on coronary artery disease (CAD) associated with Chlamydia
      pneumoniae (CP) infection. BACKGROUND: It was suggested that CP was associated
      with CAD. However, genetic factors involved in CAD associated with CP infection
      are unknown. METHODS: We evaluated CP immunoglobulin G (IgG) seropositivity and
      IL-1 beta (a C/T transition at -511) and IL-1 receptor antagonist (IL-1Ra) (a
      variable-number repeat in intron 2) gene polymorphisms in 292 patients undergoing
      coronary angiography. RESULTS: Seropositivity for CP was present in 61% of
      patients with CAD versus 51% without CAD (p = NS). The percentage of patients
      having IL-1 beta (-511) C/C genotype and/or IL-1Ra (intron 2) 2- or 3-repeat
      allele was higher in patients with CAD than without CAD (29 vs. 16%, p < 0.025).
      To clarify the effects of these CAD-associated variants (IL-1 beta C/C and/or IL
      1Ra 2- or 3-repeat), patients were divided into four groups. A stepwise increase
      in CAD prevalence was observed depending on CP seropositivity and the variants.
      Odds ratios (ORs) for CAD were 1.4 in the group with seropositivity alone, 1.7
      with the variants alone and 3.8 with seropositivity and the variants. Such
      variants were associated with CAD in both patients with and without
      seropositivity. Interestingly, high prevalence of myocardial infarction (MI) was
      confined to the group with seropositivity and the variants (OR, 2.8). The
      variants were associated with MI only in patients with CP seropositivity.
      CONCLUSIONS: The IL-1 gene polymorphisms were found to play a role in the
      development of CAD, especially MI, in patients with CP infection.

PMID- 11527623
TI  - Plaque burden, arterial remodeling and plaque vulnerability: determined by
      systemic factors?
AB  - OBJECTIVES: This study was designed to determine whether arterial remodeling and
      plaque vulnerability are influenced by systemic factors. BACKGROUND:
      Atherosclerotic luminal narrowing is caused by gradual plaque growth and arterial
      remodeling. In the acute phase, luminal narrowing may be accelerated by acute
      thrombus formation, usually precipitated by rupture of a vulnerable plaque.
      METHODS: Femoral arteries were obtained from elderly individuals at autopsy.
      Pairs of atherosclerotic femoral arteries from 42 individuals were examined. The
      arteries were divided in 1-cm intervals. Plaque size, the mode of arterial
      remodeling and histopathologic characteristics of plaque vulnerability (lipid
      rich core and plaque inflammation) were compared between right and left femoral
      arteries obtained from the same individual. A role for systemic factors was
      assumed if a phenomenon was equally present in both arteries. RESULTS: There was
      concordance in average plaque size (r(2) = 0.5, p < 0.001), expansive remodeling
      (kappa = 0.42, p = 0.007) and occurrence of plaques containing a large lipid-rich
      core (kappa = 0.60, p = 0.001), but no concordance in plaque inflammation (kappa
      = 0.067, p = 0.61) between right and left arteries. CONCLUSIONS: These results
      suggest that not only the amount of atherosclerosis, but also arterial remodeling
      and lipid deposition in plaques, are influenced by systemic factors. The
      nonhomogeneous distribution of inflammation in atherosclerotic arteries supports
      the hypothesis that plaque inflammation is locally affected.

PMID- 11527624
TI  - Angiotensin-converting enzyme inhibition is associated with reduced troponin
      release in non-ST-elevation acute coronary syndromes.
AB  - OBJECTIVES: This study was done to determine the effects of angiotensin
      converting enzyme (ACE) inhibition and other clinical factors on troponin release
      in non-ST-elevation acute coronary syndrome (ACS). BACKGROUND: Troponin is now
      widely used as a marker of risk in ACS, but determinants of its release have not
      been defined. METHODS: This was a prospective cohort study of 301 consecutive
      patients admitted with non-ST-elevation ACS. Baseline clinical data were
      recorded, ACE gene polymorphism was determined and serial blood samples were
      obtained for troponin-I assay. RESULTS: Significant troponin-I release (>0.1
      microg/l) was detected in 93 (31%) patients. Pretreatment with ACE inhibitors,
      recorded in 53 patients (17.6%), independently reduced the odds of troponin-I
      release (odds ratio 0.25; 95% confidence intervals 0.10 to 0.64) and was
      associated with lower maximum troponin-I concentrations (median [interquartile
      range]) compared with patients not pretreated with ACE inhibitors (0.44 microg/l
      [0.19 to 2.65 microg/l] vs. 4.18 microg/l [0.91 to 12.41 microg/l], p = 0.01).
      Pretreatment with aspirin, recorded in 173 patients (57.5%), did not
      significantly reduce the odds of troponin-I release after adjustment but was
      associated with lower maximum troponin-I concentrations compared with patients
      not pretreated with aspirin (2.31 microg/l [0.72 to 8.02 microg/l] vs. 5.85
      microg/l [1.19 to 12.79 microg/l], p = 0.05). The ACE genotyping (n = 268) showed
      81 patients (30%) DD homozygous and 77 (29%) II homozygous. There was no
      association between ACE genotype and troponin release. CONCLUSIONS: We conclude
      that ACE inhibition reduces troponin release in non-ST-elevation ACS. This is
      likely to be mediated by the beneficial effects of treatment on vascular
      reactivity and the coagulation system.

PMID- 11527625
TI  - Gender and survival: a population-based study of 201,114 men and women following
      a first acute myocardial infarction.
AB  - OBJECTIVES: We tested the hypotheses that the effect of gender on short-term case
      fatality following a first admission for acute myocardial infarction (AMI) varies
      with age, and that this effect is offset by differences in the proportion of men
      and women who survive to reach hospital. BACKGROUND: Evidence is conflicting
      regarding the effect of gender on prognosis after AMI. METHODS: All 201,114 first
      AMIs between 1986 and 1995 were studied. Both 30-day and 1-year case fatality
      were analyzed for the 117,749 patients hospitalized and for all first AMIs,
      including deaths before hospitalization. The effect of gender and its interaction
      with age on survival was examined using multivariate modeling. RESULTS: Gender
      based differences in survival varied according to age in hospitalized patients,
      with younger women having higher 30-day case fatality than men (e.g., <55 years,
      women 6.5% vs. 4.8% men, p < 0.0001). When deaths from first AMI before
      hospitalization were included in 30-day case fatality, women were less likely to
      die (adjusted odds ratio 0.9, confidence interval 0.89 to 0.93). Gender was not
      an independent predictor of one-year survival (p = 0.16). CONCLUSIONS: Female
      gender increases the probability of surviving to reach hospital, and this
      outweighs the excess risk of death occurring in younger women following
      hospitalization. Overall, men have a higher 30-day case fatality than women.
      Women do not fare worse than men after AMI when age and other factors are taken
      into account. However, men are more likely to die before hospitalization.

PMID- 11527626
TI  - Acute myocardial infarction in the elderly: differences by age.
AB  - OBJECTIVES: We evaluated the clinical characteristics and outcomes of elderly
      patients hospitalized with acute myocardial infarction (AMI) to describe
      differences by age. BACKGROUND: Elderly patients with AMI are perceived as a
      homogeneous population, though the extent by which clinical characteristics vary
      among elderly patients has not been well described. METHODS: Data from 163,140
      hospital admissions of Medicare beneficiaries age > or =65 years between 1994 and
      1996 with AMI at U.S. hospitals were evaluated for differences in clinical
      characteristics and mortality across five age-based strata (in years): 65 to 69,
      70 to 74, 75 to 79, 80 to 84 and > or =85. RESULTS: Older age was associated with
      a greater proportion of patients with functional limitations, heart failure,
      prior coronary disease and renal insufficiency and a lower proportion of male and
      diabetic patients. Of note, the proportion of patients presenting with chest pain
      within 6 h of symptom onset, and with ST-segment elevation, was lower in each
      successive age group. Thirty-day mortality rates were higher in older age groups
      (65 to 69: 10.9%, 70 to 74: 14.1%, 75 to 79: 18.5%, 80 to 84: 23.2%, > or =85:
      31.2%, p = 0.001 for trend). The effect of age persisted but was attenuated after
      adjustment for differences in patient characteristics; similar trends were
      observed for one-year mortality. CONCLUSIONS: Our data indicate significant age
      associated differences in clinical characteristics in elderly patients with AMI,
      which account for some of the age-associated differences in mortality. The
      practice of grouping older patients together as a single age group may obscure
      important age-associated differences.

PMID- 11527627
TI  - Changes in heart rate and heart rate variability before ambulatory ischemic
      events(1).
AB  - OBJECTIVES: The aim of this study was to determine the time course of autonomic
      nervous system activity preceding ambulatory ischemic events. BACKGROUND: Vagal
      withdrawal can produce myocardial ischemia and may be involved in the genesis of
      ambulatory ischemic events. We analyzed trajectories of heart rate variability
      (HRV) 1 h before and after ischemic events, and we examined the role of exercise
      and mental stress in preischemic autonomic changes. METHODS: Male patients with
      stable coronary artery disease (n = 19; 62.1 +/- 9.3 years) underwent 48-h
      ambulatory electrocardiographic monitoring. Frequency domain HRV measures were
      assessed for 60 min before and after each of 68 ischemic events and during
      nonischemic heart rate-matched control periods. RESULTS: High-frequency HRV
      decreased from -60, -20 to -10 min before ischemic events (4.8 +/- 1.3; 4.6 +/-
      1.3; 4.4 +/- 1.2 ln [ms(2)], respectively; p = 0.04) and further from -4, -2 min,
      until ischemia (4.4 +/- 1.3; 4.1 +/- 1.3; 3.7 +/- 1.2 ln [ms(2)]; p's < 0.01).
      Low frequency HRV decreases started at -4 min (p < 0.05). Ischemic events
      occurring at high mental activities were preceded by depressed high frequency HRV
      levels compared with events at low mental activity (p = 0.038 at -4 min, p =
      0.045 at -2 min), whereas the effects of mental activities were not observed
      during nonischemic control periods. Heart rate variability measures remained
      significantly decreased for 20 min after recovery of ST-segment depression when
      events were triggered by high activity levels. CONCLUSIONS: Autonomic changes
      consistent with vagal withdrawal can act as a precipitating factor for daily life
      ischemia, particularly in episodes triggered by mental activities.

PMID- 11527628
TI  - Double potentials along the ablation line as a guide to radiofrequency ablation
      of typical atrial flutter.
AB  - OBJECTIVES: The purpose of this study was to determine the characteristics of
      double potentials (DPs) that are helpful in guiding ablation within the cavo
      tricuspid isthmus. BACKGROUND: Double potentials have been considered a reliable
      criterion of cavo-tricuspid isthmus block in patients undergoing radiofrequency
      ablation of typical atrial flutter (AFL). However, the minimal degree of
      separation of the two components of DPs needed to indicate complete block has not
      been well defined. METHODS: Radiofrequency ablation was performed in 30 patients
      with isthmus-dependent AFL. Bipolar electrograms were recorded along the ablation
      line during proximal coronary sinus pacing at sites at which radiofrequency
      ablation resulted in incomplete or complete isthmus block. RESULTS: Double
      potentials were observed at 42% of recording sites when there was incomplete
      isthmus block, compared with 100% of recording sites when the block was complete.
      The mean intervals separating the two components of DPs were 65 +/- 21 ms and 135
      +/- 30 ms during incomplete and complete block, respectively (p < 0.001). An
      interval separating the two components of DPs (DP(1-2) interval) <90 ms was
      always associated with a local gap, whereas a DP(1-2) interval > or =110 ms was
      always associated with local block. When the DP(1-2) interval was between 90 and
      110 ms, an isoelectric segment within the DP and a negative polarity in the
      second component of the DP were helpful in indicating local isthmus block. A DP(1
      2) interval > or =90 ms with a maximal variation of 15 ms along the entire
      ablation line was an indicator of complete block in the cavo-tricuspid isthmus.
      CONCLUSIONS: Detailed analysis of DPs is helpful in identifying gaps in the
      ablation line and in distinguishing complete from incomplete isthmus block in
      patients undergoing radiofrequency ablation of typical AFL.

PMID- 11527629
TI  - Anasarca-mediated attenuation of the amplitude of electrocardiogram complexes: a
      description of a heretofore unrecognized phenomenon.
AB  - OBJECTIVES: The relationship between the changes of weight (WT) and
      electrocardiogram (ECG) QRS amplitude in patients with anasarca (AN) was
      evaluated. BACKGROUND: Attenuation of the ECG voltage occurs as the electrical
      current spreads from the epicardium to the body surface. The voltage registered
      is a function of the cardiac potentials, the electrical resistivities of the
      intervening tissues and the orientation of the ECG leads with respect to the
      direction of propagation of excitation. Lung congestion and pericardial and
      pleural effusions can cause attenuation in the ECG potentials; additionally, a
      similar change was recently observed in patients with AN. METHODS: A prospective
      study of this phenomenon in 28 patients with a critical illness was carried out.
      Electrocardiograms and patients' WTs were recorded daily. Pericardial effusions
      were excluded by serial echocardiograms. The sums of the amplitude of QRS
      complexes from the 12 ECG leads (Sigma QRS) were correlated with the
      corresponding WTs. Intracardiac ECGs, done in three patients, were correlated
      with surface ECGs. RESULTS: Admission WT was 148.9 +/- 37.8 lbs, and it peaked to
      197.8 +/- 52.3 lbs (p = 0.0005). Admission Sigma QRS was 120.2 +/- 41.6 mm and
      dropped to 54.8 +/- 26.9 mm at time of peak WT (p = 0.0005). Regression of Sigma
      QRS on WT revealed an r = 0.61 and a p = 0.0005. Subsequent WT loss in 13
      patients (from 219.0 +/- 40.7 lbs to 179.5 +/- 41.7 lbs, p = 0.001) led to an
      increase of Sigma QRS from 53.5 +/- 24.5 mm to 86.8 +/- 38.2 mm (p = 0.001).
      Intracardiac ECGs remained stable, while surface ECGs changed with perturbations
      of WT. CONCLUSIONS: Attenuation of ECG voltage in patients with AN correlates
      with WT gain, and it can be attributed to a shunting of the cardiac potentials
      due to the low resistance of the AN fluid.

PMID- 11527630
TI  - The prevalence, incidence and prognostic value of the Brugada-type
      electrocardiogram: a population-based study of four decades.
AB  - OBJECTIVES: We sought to demonstrate the prevalence, incidence and prognostic
      value of the Brugada-type electrocardiogram (ECG) in a general population.
      BACKGROUND: The Brugada syndrome is characterized by evidence of right bundle
      branch block and ST segment elevation in the right precordial leads, as well as
      sudden death caused by ventricular fibrillation. However, the natural history of
      the Brugada-type ECG remains unclear. METHODS: We investigated 4,788 subjects
      (1,956 men and 2,832 women) who were <50 years old in 1958 and had undergone
      biennial health examinations, including electrocardiography, through 1999. The
      Brugada-type ECG was defined as a terminal r' wave in lead V(1) and ST segment
      elevation > or =0.1 mV in leads V(1) and V(2). Unexpected death was defined as
      sudden death or unexplained accidental death. RESULTS: There were a total of 32
      Brugada-type ECG cases; the prevalence and incidence were 146.2 in 100,000
      persons and 14.2 persons per 100,000 person-years, respectively. The incidence
      was nine times higher among men than women, and the average age at presentation
      was 45 +/- 10.5 years. The Brugada-type ECG appeared intermittently in most cases
      and was found in 26% of subjects who died unexpectedly. Cox survival analysis
      revealed that mortality from unexpected death was significantly higher in
      subjects with a Brugada-type ECG than in control subjects (p < 0.01). Unexpected
      deaths were more frequent among subjects with the Brugada-type ECG who had a
      history of syncope (p < 0.05). CONCLUSIONS: The Brugada-type ECG is not a very
      rare condition in the adult Japanese population. Subjects with a Brugada-type ECG
      have an increased risk of unexpected death.

PMID- 11527631
TI  - Prevalence and mortality of the Brugada-type electrocardiogram in one city in
      Japan.
AB  - OBJECTIVES: We sought to study the prevalence and mortality of subjects
      exhibiting the Brugada-type electrocardiogram (ECG) in a community-based
      population in Japan. BACKGROUND: The Brugada syndrome has been associated with
      sudden death in subjects without structural heart disease. Hospital-based studies
      showed 11% to 38% annual fatal arrhythmic events in patients with the Brugada
      syndrome. METHODS: Prevalence and mortality of the Brugada-type ECG were studied
      in subjects who had ECGs during a health examination in Moriguchi, Osaka, Japan.
      Information about death and relocation from Moriguchi city was obtained
      prospectively. RESULTS: The Brugada-type ECG was found in 98 of 13,929 study
      subjects (0.70%, 95% confidence interval [CI]: 0.57% to 0.86%). The typical coved
      type with an rsR' pattern in V(1) lead ("typical" Brugada-type) was found in
      0.12% of subjects (95% CI: 0.07% to 0.20%). The prevalence for male subjects with
      the Brugada-type ECG (81%) was significantly higher than it was for those without
      (26%, p < 0.0001). In male subjects, the Brugada-type ECG was found in 2.14% (95%
      CI: 1.70% to 2.66%), and the "typical" Brugada-type was found in 0.38% (95% CI:
      0.21% to 0.64%). After 2.6 +/- 0.3 years of follow-up, there was 1 death (1.0%,
      95% CI: 0.03% to 5.6%) of a subject with the Brugada-type ECG, whereas there were
      139 deaths (1.0%, 95% CI: 0.85% to 1.2%) of those without the Brugada-type ECG (p
      = 0.9943, log-rank test). CONCLUSIONS: A substantial number of the Brugada-type
      ECG were observed in subjects in a community-based population in Japan,
      especially in men. The total mortality of subjects with the Brugada-type ECG did
      not differ from the mortality of those without the Brugada-type ECG in a
      community-based population.

PMID- 11527632
TI  - Brugada syndrome: manifest, concealed, "asymptomatic," suspected and simulated.

PMID- 11527633
TI  - Prevalence of left atrial chamber and appendage thrombi in patients with atrial
      flutter and its clinical significance.
AB  - OBJECTIVES: The study was done to assess the prevalence of left atrial (LA)
      chamber and appendage thrombi in patients with atrial flutter (AFl) scheduled for
      electrophysiologic study (EPS), to evaluate the prevalence of thromboembolic
      complications after transesophageal echocardiographic (TEE)-guided restoration of
      sinus rhythm and to evaluate clinical risk factors for a thrombogenic milieu.
      BACKGROUND: Recent studies showed controversial results on the prevalence of
      atrial thrombi and the risk of thromboembolism after restoring sinus rhythm in
      patients with AFl. METHODS: Between 1995 and 1999, patients with AFl who were
      scheduled for EPS were included in the study. After transesophageal assessment of
      the left atrial appendage and exclusion of thrombi, an effective anticoagulation
      was initiated and patients underwent EPS within 24 h. RESULTS: We performed 202
      EPSs (radiofrequency catheter ablation, n = 122; overdrive stimulation, n = 64;
      electrical cardioversion, n = 16) in 139 consecutive patients with AFl. Fifteen
      patients with a thrombogenic milieu were identified. All of them had paroxysmal
      atrial fibrillation (AF). Transesophageal echocardiography revealed LA thrombi in
      two cases (1%). After EPS no thromboembolic complications were observed. Diabetes
      mellitus, arterial hypertension and a decreased left ventricular ejection
      fraction were found to be independent risk factors associated with a thrombogenic
      milieu. CONCLUSIONS: The findings of a low prevalence of LA appendage thrombi
      (1%) in patients with AFl and a close correlation between a history of previous
      embolism and paroxysmal AF support the current guidelines that patients with pure
      AFl do not require anticoagulation therapy, whereas patients with AFl and
      paroxysmal AF should receive anticoagulation therapy. In addition, the presence
      of clinical risk factors should alert the physician to an increased likelihood
      for a thrombogenic milieu.

PMID- 11527634
TI  - Is atrial flutter a risk factor for stroke?

PMID- 11527635
TI  - The relationship between obesity and mortality in patients with heart failure.
AB  - OBJECTIVES: The study aimed to evaluate the role of obesity in the prognosis of
      patients with heart failure (HF). BACKGROUND: Previous reports link obesity to
      the development of HF. However, the impact of obesity in patients with
      established HF has not been studied. METHODS: We analyzed 1,203 patients with
      advanced HF followed in a comprehensive HF management program. The patients were
      subclassified into categories of body mass index (BMI) defined as: underweight
      BMI <20.7 (n = 164), recommended BMI 20.7 to 27.7 (n = 692), overweight BMI 27.8
      to 31 (n = 168) and obese BMI >31 (n = 179). This sample size allows the
      detection of small effects (0.02), with a power of 0.80 and an alpha level of
      0.05 for comparing one-year survival between BMI groups. RESULTS: The four BMI
      groups had similar profiles in terms of ejection fraction (mean 0.22), sodium,
      creatinine and smoking. The obese and overweight groups had significantly higher
      rates of hypertension and diabetes, as well as higher levels of cholesterol,
      triglycerides and low density lipoprotein cholesterol. The four BMI groups had
      similar survival rates. Ejection fraction, HF etiology and angiotensin-converting
      enzyme inhibitor use predicted survival on univariate analysis (p < 0.01),
      although BMI did not. On multivariate analysis, cardiopulmonary exercise tests,
      pulmonary capillary wedge pressure and serum sodium were strong predictors of
      survival (p < 0.05). Higher BMI was not a risk factor for increased mortality,
      but was associated with a trend toward improved survival. CONCLUSIONS: In a large
      cohort of patients with advanced HF of multiple etiologies, obesity is not
      associated with increased mortality and may confer a more favorable prognosis.
      Further studies need to delineate whether weight loss promotion in medically
      optimized patients with HF is a worthwhile therapeutic goal.

PMID- 11527636
TI  - Cardiac cycle-dependent changes in aortic area and distensibility are reduced in
      older patients with isolated diastolic heart failure and correlate with exercise
      intolerance.
AB  - OBJECTIVES: The goal of this study was to determine if cardiac cycle-dependent
      changes in proximal thoracic aortic area and distensibility are associated with
      exercise intolerance in elderly patients with diastolic heart failure (DHF).
      BACKGROUND: Aortic compliance declines substantially with age. We hypothesized
      that a reduction in cardiac cycle-dependent changes in thoracic aortic area and
      distensibility (above that which occurs with aging) could be associated with the
      exercise intolerance that is prominent in elderly diastolic heart failure
      patients. METHODS: Thirty subjects (20 healthy individuals [10 < 30 years of age
      and 10 > 60 years of age] and 10 individuals > the age of 60 years with DHF)
      underwent a magnetic resonance imaging (MRI) study of the heart and proximal
      thoracic aorta followed within 48 h by maximal exercise ergometry with expired
      gas analysis. RESULTS: The patients with DHF had higher resting brachial pulse
      and systolic blood pressure, left ventricular mass, aortic wall thickness and
      mean aortic flow velocity, and, compared with healthy older subjects, they had a
      significant reduction in MRI-assessed cardiac cycle-dependent change in aortic
      area and distensibility (p < 0.0001) that correlated with diminished peak
      exercise oxygen consumption (r = 0.79). After controlling for age and gender in a
      multivariate analysis, thoracic aortic distensibility was a significant predictor
      of peak exercise oxygen consumption (p < 0.04). CONCLUSIONS: Older patients with
      isolated DHF have reduced cardiac cycle-dependent changes in proximal thoracic
      aortic area and distensibility (beyond that which occurs with normal aging), and
      this correlates with and may contribute to their severe exercise intolerance.

PMID- 11527637
TI  - Diastolic heart failure, diastolic left ventricular dysfunction and exercise
      intolerance.

PMID- 11527638
TI  - Effect of age on mortality, hospitalizations and response to digoxin in patients
      with heart failure: the DIG study.
AB  - OBJECTIVES: This study was designed to determine the effect of increasing age on
      mortality, hospitalizations and digoxin side effects in patients with heart
      failure (HF), and to determine whether the effect of digoxin on clinical outcomes
      varies as a function of age. BACKGROUND: The incidence and prevalence of HF
      increase with advancing age, but there are limited data on the clinical course
      and response to specific therapeutic interventions in elderly patients with HF.
      METHODS: The Digitalis Investigation Group (DIG) study was a prospective,
      randomized clinical trial involving 7,788 patients with HF randomized to digoxin
      or placebo and followed for an average of 37 months. In the present analysis,
      patients were stratified into five age categories: <50 years (n = 841), 50 to 59
      years (n = 1,545), 60 to 69 years (n = 2,885), 70 to 79 years (n = 2,092) and >
      or =80 years (n = 425). Interactions between age and the following clinical
      outcomes were examined: total mortality, all-cause hospitalizations, HF
      hospitalizations, the composite of HF death or HF hospitalization,
      hospitalization for suspected digoxin toxicity and withdrawal from therapy
      because of side effects. RESULTS: Increasing age was an independent risk factor
      for total mortality, all-cause hospitalization, HF hospitalization, HF death or
      hospital admission, hospitalization for suspected digoxin toxicity and withdrawal
      from digoxin therapy (all p < 0.001). However, there were no significant
      interactions between age and digoxin treatment with respect to any of the major
      clinical end points. CONCLUSIONS: Increasing age is associated with progressively
      worse clinical outcomes in patients with HF. However, the beneficial effects of
      digoxin in reducing all-cause admissions, HF admissions, and HF death or
      hospitalization are independent of age. Thus, digoxin remains a useful agent for
      the adjunctive treatment of HF due to impaired left ventricular systolic function
      in patients of all ages.

PMID- 11527639
TI  - Simvastatin treatment is associated with improvement in coronary endothelial
      function and decreased cytokine activation in patients after heart
      transplantation.
AB  - OBJECTIVES: This study was designed to assess the association between 3-hydroxy-3
      methylglutaryl coenzyme A (HMG-CoA) reductase inhibition, coronary endothelial
      function and cytokine activation in heart transplant recipients without
      angiographically detectable disease. BACKGROUND: Coronary endothelial dysfunction
      contributes to cardiac allograft vasculopathy. The vasoprotective effects of
      statins in heart transplant recipients may include restoration of endothelial
      function and suppression of allograft inflammatory activity. METHODS: Heart
      transplant recipients (one to three years after heart transplant) were divided
      into three groups based on the total cholesterol levels: group 1 (n = 21),
      patients with a history of hypercholesterolemia adequately controlled with
      simvastatin; group 2 (n = 19), patients with hypercholesterolemia not adequately
      treated with simvastatin; and group 3 (n = 40), patients without
      hypercholesterolemia. Coronary vasomotor function and intimal thickness as well
      as coronary sinus and aortic cytokine concentrations (tumor necrosis factor [TNF]
      alpha, interleukin [IL]-6 and soluble IL-2 receptor) were investigated. In a
      prospective one-year follow-up study, changes in coronary endothelial function
      and cytokine levels were compared between 11 hypercholesterolemic patients
      treated with simvastatin and 9 controls. RESULTS: Epicardial and microvascular
      endothelial functions were better in groups 1 and 3 than they were in group 2 (p
      < 0.01 and p < 0.05). Transcardiac IL-6 and TNF-alpha gradients were
      significantly increased in groups 2 and 3 compared with group 1 (IL-6: p < 0.05;
      TNF-alpha: p < 0.01). Plaque areas were significantly increased in groups 1 and 2
      (p < 0.05 vs. group 3), whereas lumen area was increased in group 2 compared with
      group 1 (p < 0.05), demonstrating adaptive vascular remodeling. In patients
      treated with simvastatin, coronary endothelial function and cardiac cytokine
      activity significantly improved during the one-year follow-up. CONCLUSIONS:
      Inhibition of allograft inflammatory activity and attenuation of the coronary
      endothelial dysfunction observed in cardiac transplant recipients during
      treatment with simvastatin may represent an important mechanism by which HMG-CoA
      reductase inhibitors protect against the development of cardiac allograft
      vasculopathy.

PMID- 11527640
TI  - Echocardiographic characteristics and outcome of straddling mitral valve.
AB  - OBJECTIVES: This study sought to characterize the echocardiographic features of
      straddling mitral valve (SMV) and to determine its surgical implications and
      midterm outcome in a large clinical cohort. BACKGROUND: Despite a relatively
      large body of literature on the postmortem anatomy of SMV, there is a paucity of
      information regarding its echocardiographic features, surgical implications and
      preoperative predictors of outcome. METHODS: A retrospective review identified 46
      patients with SMV between 1982 and 1999 who underwent echocardiography and
      surgery and had follow-up data. A detailed review of the echocardiograms,
      surgical reports and all pertinent records was undertaken. RESULTS: Review of the
      echocardiograms revealed a widely varying anatomy among the study patients.
      However, four distinct groups with relatively uniform morphologic features could
      be distinguished on the basis of segmental analysis. Cardiac malposition
      associated with right ventricular hypoplasia, superior-inferior ventricles and
      criss-cross atrioventricular relations were common among patients with [S,D,L] (S
      = visceroatrial situs solitus, D = D-ventricular loop, L = L-malposition of the
      great arteries) (n = 6) and [S,L,D] (n = 5) segmental combinations but were rare
      among patients with [S,D,D] (n = 26) and [S,L,L] (n = 9) combinations. Surgical
      management consisted of a functional single-ventricle palliation in 38 patients
      (83%) and biventricular repair in 8 patients (17%). Overall mortality was 22%,
      but none of the seven patients who were operated on during the cohort's last five
      years (1994 to 1999) has died. By multivariate analysis, noncommitted ventricular
      septal defect was the strongest independent predictor of death (relative risk =
      10.2), followed by multiple ventricular septal defects (relative risk = 4.7).
      CONCLUSIONS: This study demonstrates that echocardiography provides detailed
      noninvasive imaging of the complex anatomic features of SMV and its associated
      anomalies. Anatomic classification based on segmental analysis allows the
      distinction of four groups with more uniform morphologic features. Although a
      biventricular approach is feasible in selected patients, a functional
      univentricular palliation is indicated in those with major straddling and
      markedly hypoplastic ventricles.

PMID- 11527641
TI  - Aortic valve sclerosis and aortic atherosclerosis: different manifestations of
      the same disease? Insights from a population-based study.
AB  - OBJECTIVES: The aim of this study was to examine the association between
      atherosclerosis risk factors, aortic atherosclerosis and aortic valve
      abnormalities in the general population. BACKGROUND: Clinical and experimental
      studies suggest that aortic valve sclerosis (AVS) is a manifestation of the
      atherosclerotic process. METHODS: Three hundred eighty-one subjects, a sample of
      the Olmsted County (Minnesota) population, were examined by transthoracic and
      transesophageal echocardiography. The presence of AVS (thickened valve leaflets),
      elevated transaortic flow velocities and aortic regurgitation (AR) was
      determined. The associations between atherosclerosis risk factors, aortic
      atherosclerosis (imaged by transesophageal echocardiography) and aortic valve
      abnormalities were examined. RESULTS: Age, male gender, body mass index (odds
      ratio [OR]: 1.07 per kg/m(2); 95% confidence interval [CI]: 1.02 to 1.12),
      antihypertensive treatment (OR: 1.93; CI: 1.12 to 3.32) and plasma homocysteine
      levels (OR: 1.89 per twofold increase; CI: 0.99 to 3.61) were independently
      associated with an increased risk of AVS. Age, body mass index and pulse pressure
      (OR: 1.21 per 10 mm Hg; CI: 1.00 to 1.46) were associated with elevated (upper
      quintile) transaortic velocities, whereas only age was independently associated
      with AR. Sinotubular junction sclerosis (p = 0.001) and atherosclerosis of the
      ascending aorta (p = 0.03) were independently associated with AVS and elevated
      transaortic velocities, respectively. CONCLUSIONS: Atherosclerosis risk factors
      and proximal aortic atherosclerosis are independently associated with aortic
      valve abnormalities in the general population. These observations suggest that
      AVS is an atherosclerosis-like process involving the aortic valve.

PMID- 11527642
TI  - Discrete subaortic stenosis in adults: increased prevalence and slow rate of
      progression of the obstruction and aortic regurgitation.
AB  - OBJECTIVES: We sought to determine the prevalence and rate of progression of left
      ventricular outflow tract obstruction (LVOTO) and aortic regurgitation (AR) in
      adults with discrete subaortic stenosis (DSS). BACKGROUND: Discrete subaortic
      stenosis is an uncommon form of LVOTO, with rapid hemodynamic progression in
      children, but the prevalence and rate of progression in adults have not been
      studied so far. METHODS: The prevalence of DSS was determined in 2,057
      consecutive adults diagnosed with congenital heart disease (CHD). The
      relationship between LVOTO on Doppler echocardiography and patient age was
      analyzed. Sequential changes in LVOTO and AR were determined for patients with
      two or more Doppler echocardiograms obtained with at least a two-year interval.
      RESULTS: A total of 134 adults (mean age 31 +/- 17 years) were diagnosed with
      DSS. The prevalence was 6.5% for all adults with CHD. Sixty patients (44%) had
      other associated CHD. The mean age of 29 patients who had undergone an operation
      for DSS during their adult life (56 +/- 15 years) was significantly higher than
      that of 64 patients (27 +/- 13 years) who had not required a surgical
      intervention (p < 0.0001). A significant relationship between LVOTO and patient
      age (r = 0.61, p < 0.0001) was found: 21 +/- 16 mm Hg in patients <25 years old,
      51 +/- 47 mm Hg for those between 25 and 50 years old, and 78 +/- 36 mm Hg for
      those >50 years old. The LVOTO increased from 39.2 +/- 28 to 46.8 +/- 34 mm Hg (p
      = 0.01) during a mean follow-up of 4.8 +/- 1.8 years in 25 patients. The slope of
      the change in LVOTO was 2.25 +/- 4.7 mm Hg per year of follow-up. Aortic
      regurgitation was detected by color Doppler imaging in 109 patients (81%), but it
      was hemodynamically significant in <20%. An increase in the mean degree of AR
      over time was not significant (baseline: 1.3 +/- 0.8; follow-up: 1.5 +/- 0.9; p =
      0.096). CONCLUSIONS: The prevalence of DSS is increasing in adults due to the
      greater number of repaired CHDs that develop into evolutive DSS. In contrast to
      infants and children, adults with DSS show a slow rate of LVOTO progression.
      Aortic regurgitation is a common but usually mild and nonprogressive consequence.
      The current indications for surgical intervention should be revised.

PMID- 11527643
TI  - Natural history of discrete subvalvar aortic stenosis: management implications.

PMID- 11527644
TI  - Pressure-guided nonsurgical myocardial reduction induced by small septal
      infarctions in hypertrophic obstructive cardiomyopathy.
AB  - OBJECTIVES: We sought to assess the safety and efficacy of pressure-guided
      nonsurgical myocardial reduction (NSMR) with the induction of small septal
      infarctions in patients with hypertrophic obstructive cardiomyopathy (HOCM).
      BACKGROUND: Nonsurgical myocardial reduction has been shown to decrease left
      ventricular outflow tract (LVOT) obstruction and to improve symptoms in patients
      with HOCM. Infarct sizes differ considerably among studies published so far.
      METHODS: In 50 patients, the LVOT gradient was invasively determined at the time
      of the intervention, four to six months (n = 49) and 12 to 18 months (n = 25)
      after NSMR. New York Heart Association functional class and quality of life were
      assessed by using a standard questionnaire. Exercise capacity was tested by spiro
      ergometry. Left ventricular (LV) mass was determined by electron beam computed
      tomography. RESULTS: Small septal infarctions (mean creatine kinase value 413 +/-
      193 U/l) resulted in a sustained decrease in LVOT gradients, from 80 +/- 33 to 18
      +/- 17 mm Hg after four to six months (p < 0.001, n = 49) and to 17 +/- 15 mm Hg
      (p < 0.001, n = 25) after 12 to 18 months. Nonsurgical myocardial reduction was
      followed by a decrease in LV hypertrophy, which was associated with a sustained
      increase in exercise capacity, as well as improvement in quality of life.
      CONCLUSIONS: Pressure-guided NSMR inducing small septal infarctions was
      sufficient to result in a sustained decrease in LVOT obstruction and to improve
      symptoms. The incidence of complications, such as complete heart block with
      necessary permanent pacemaker implantation (<10%), seems to be diminished by
      minimizing the infarct size.

PMID- 11527645
TI  - Differential effects of pentaerythritol tetranitrate and nitroglycerin on the
      development of tolerance and evidence of lipid peroxidation: a human in vivo
      study.
AB  - OBJECTIVES: We investigated the development of nitrate tolerance after continuous
      exposure to nitroglycerin (GTN) as compared with pentaerythritol tetranitrate
      (PETN) in humans. BACKGROUND: Sustained therapy with GTN causes tolerance and has
      been associated with increased production of free oxygen radicals by the
      endothelium. Pentaerythritol tetranitrate is an organic nitrate that has been
      used in the therapy of angina. There have been no investigations concerning the
      development of tolerance to PETN in humans. Animal investigations suggested that
      continuous therapy with PETN does not cause increased free radical production or
      hemodynamic tolerance. METHODS: We randomized 30 healthy volunteers to continuous
      GTN (0.6 mg/h/24 h), long-acting PETN (60 mg orally three times a day) or no
      treatment (control group) for seven days. We studied systemic blood pressure
      responses and venous volume responses to GTN with strain-gauge plethysmography.
      The levels of cytotoxic aldehydes and isoprostanes were measured as markers of
      free radical-mediated lipid peroxidation. RESULTS: Tolerance, as demonstrated by
      blood pressure and forearm plethysmography, developed in the GTN group and was
      absent in the PETN group (p < 0.05). Therapy with GTN was associated with a
      significant increase in plasma markers of lipid peroxidation. This response was
      not observed in those treated with PETN (isoprostanes: control: 38 +/- 5; GTN: 59
      +/- 6; PETN: 38 +/- 3 microg/ml; p < 0.005). CONCLUSIONS: Treatment with PETN
      does not cause tolerance and is not associated with evidence of increased free
      radical production.

PMID- 11527646
TI  - The effect of combined aerobic and resistance exercise training on vascular
      function in type 2 diabetes.
AB  - OBJECTIVES: The purpose of this study was to examine whether exercise training
      stimulates a generalized improvement in vascular function in patients with type 2
      diabetes mellitus. BACKGROUND: Exercise is often recommended for patients with
      type 2 diabetes to improve physical conditioning and glycemic control. This study
      examined the effect of eight weeks of exercise training on conduit and resistance
      vessel function in patients with type 2 diabetes, using a randomized crossover
      design. METHODS: Both resistance vessel endothelium-dependent and -independent
      functions were determined by forearm plethysmography and intrabrachial infusions
      of acetylcholine (ACh) and sodium nitroprusside (SNP), respectively, in 16
      patients with type 2 diabetes. Conduit vessel endothelial function was assessed
      in 15 of these patients using high-resolution ultrasound and flow-mediated
      dilation of the brachial artery; glyceryl trinitrate (GTN) was used as an
      endothelium-independent dilator. RESULTS: Flow-mediated dilation increased from
      1.7 +/- 0.5% to 5.0 +/- 0.4% following training (p < 0.001). The forearm blood
      flow ratio to ACh was significantly improved (analysis of variance, p < 0.05).
      Responses to SNP and GTN were unchanged. Endothelium-dependent vasodilation was
      enhanced in both conduit and resistance vessels. CONCLUSIONS: If endothelial
      dysfunction is an integral component of the pathogenesis of vascular disease, as
      currently believed, this study supports the value of an exercise program in the
      management of type 2 diabetes.

PMID- 11527647
TI  - Contrast echocardiography improves the accuracy and reproducibility of left
      ventricular remodeling measurements: a prospective, randomly assigned, blinded
      study.
AB  - OBJECTIVES: We sought to assess the impact of contrast injection and harmonic
      imaging, on the measure by echocardiography of left ventricular (LV) remodeling.
      BACKGROUND: Left ventricular remodeling is a precursor of LV dysfunction, but the
      impact of contrast injection and harmonic imaging on the accuracy or
      reproducibility of echocardiography is unclear. METHODS: We prospectively
      collected LV images by using simultaneous methods. Then, LV volumes were measured
      off-line, in blinded manner and in random order. The accuracy of echocardiography
      was determined in comparison to electron beam computed tomography (EBCT) in 26
      patients. The reproducibility of echocardiography was assessed by three blinded
      observers with different training levels in 32 patients. RESULTS: End-diastolic
      volume (EDV), end-systolic volume (ESV), stroke volume (SV) and ejection fraction
      (EF), as measured by EBCT (195 +/- 55, 58 +/- 24 and 137 +/- 35 ml and 71 +/- 5%,
      respectively) and echocardiography with harmonic imaging and contrast injection
      (194 +/- 51, 55 +/- 20 and 140 +/- 35 ml and 72 +/- 4%, respectively), showed no
      differences (all p > 0.15) and excellent correlations (all r > 0.87). In
      contrast, echocardiography using harmonic imaging without contrast injection
      underestimated the EBCT results (all p < 0.01). Reproducibility was superior with
      rather than without contrast injection for intraobserver and interobserver
      variabilities (all p < 0.001). Values measured by different observers were
      different without contrast injection, but were similar with contrast injection
      (all p > 0.18). Consequently, intrinsic patient differences represented a larger
      and almost exclusive proportion of global variability with contrast injection for
      EDV (94 vs. 79%), ESV (93 vs. 82%), SV (87 vs. 53%) and EF (84 vs. 41%), as
      compared with harmonic imaging without contrast injection (all p < 0.005).
      CONCLUSIONS: For assessment of LV remodeling, echocardiography with harmonic
      imaging and contrast injection improved the accuracy and reproducibility, as
      compared with imaging without contrast injection. With contrast injection,
      variability was almost exclusively due to intrinsic patient differences.
      Therefore, when evaluation of LV remodeling is deemed important, assessment after
      contrast injection should be the preferred echocardiographic approach.

PMID- 11527648
TI  - Important role of endogenous norepinephrine and epinephrine in the development of
      in vivo pressure-overload cardiac hypertrophy.
AB  - OBJECTIVES: We sought to define the role of norepinephrine and epinephrine in the
      development of cardiac hypertrophy and to determine whether the absence of
      circulating catecholamines alters the activation of downstream myocardial
      signaling pathways. BACKGROUND: Cardiac hypertrophy is associated with elevated
      plasma catecholamine levels and an increase in cardiac morbidity and mortality.
      Although considerable evidence suggests that G-protein-coupled receptors are
      involved in the hypertrophic response, it remains controversial whether
      catecholamines are required for the development of in vivo cardiac hypertrophy.
      METHODS: We performed transverse aortic constriction (TAC) in dopamine beta
      hydroxylase knockout mice (Dbh(-/-), genetically altered mice that are completely
      devoid of endogenous norepinephrine and epinephrine) and littermate control mice.
      After induction of cardiac hypertrophy, the mitogen-activated protein kinase
      (MAPK) signaling pathways were measured in pressure-overloaded/wild-type and Dbh(
      /-) hearts. RESULTS: Compared with the control animals, cardiac hypertrophy was
      significantly blunted in Dbh(-/-) mice, which was not associated with altered
      cardiac function, as assessed by transthoracic echocardiography in conscious
      mice. The extracellularly regulated kinase (ERK 1/2), c-jun-NH(2)-terminal kinase
      (JNK) and p38 MAPK pathways were all activated by two- to threefold after TAC in
      the control animals. In contrast, induction of the three pathways (ERK 1/2, JNK
      and p38) was completely abolished in Dbh(-/-) mice. CONCLUSIONS: These data
      demonstrate a nearly complete requirement of endogenous norepinephrine and
      epinephrine for the induction of in vivo pressure-overload cardiac hypertrophy
      and for the activation of hypertrophic signaling pathways.

PMID- 11527649
TI  - Effects of chronic atrial fibrillation on gap junction distribution in human and
      rat atria.
AB  - OBJECTIVES: To elucidate the structural basis for the electrophysiologic
      remodeling induced by chronic atrial fibrillation (AF), we investigated
      connexin40 and connexin43 (Cx40 and Cx43) expression and distribution in atria of
      patients with and without chronic AF and in an animal model of AF with additional
      electrophysiologic investigation of anisotropy (ratio of longitudinal and
      transverse velocities). BACKGROUND: Atrial fibrillation is a common arrhythmia
      that has a tendency to become persistent. Since gap junctions provide the
      syncytial properties of the atrium, changes in expression and distribution of
      intercellular connections may accompany the chronification of AF. METHODS: Atrial
      tissues isolated from 12 patients in normal sinus rhythm at the time of cardiac
      surgery and from 12 patients with chronic AF were processed for immunohistology
      and immunoblotting for the detection of the gap junction proteins. The functional
      study of the cardiac tissue anisotropy was performed in rat atria in which AF was
      induced by 24 h of rapid pacing (10 Hz). RESULTS: Immunoblotting revealed that AF
      did not induce any significant change in Cx43 content in human atria. In
      contrast, a 2.7-fold increase in expression of Cx40 was observed in AF.
      Immunohistologic analysis indicated that AF resulted in an increase in the
      immunostaining of both connexins at the lateral membrane of human atrial cells. A
      similar spatial redistribution of the Cx43 signal was seen in isolated rat atria
      with experimentally-induced AF. In addition, AF in rat atria resulted in
      decreased anisotropy with slightly enhanced transverse conduction velocity.
      CONCLUSIONS: This experimental study showed that AF is accompanied by spatial
      remodeling of gap junctions that might induce changes in the biophysical
      properties of the tissue.

PMID- 11527650
TI  - Attenuation of interatrial conduction using right atrial septal catheter
      ablation.
AB  - OBJECTIVES: We sought to characterize a method of attenuating interatrial
      conduction using radiofrequency ablated lesions applied to the right atrial
      septum. BACKGROUND: Interatrial conduction occurs in specific zones. Recent data
      suggest that interatrial conduction can be important in triggering and sustaining
      atrial fibrillation. Therefore, a method for attenuating interatrial conduction
      may have therapeutic value. METHODS: In 13 healthy pigs, interatrial conduction
      was evaluated before and after sequential ablation of the right atrial septum,
      targeting interatrial conduction zones. In six animals, zone 1 (crista terminalis
      and limbus) was ablated first, followed by ablation of zone 2 (fossa ovalis and
      coronary sinus ostium). In the other seven animals, the order of ablation was
      reversed. Electrophysiologic and pathologic findings were correlated. RESULTS:
      After ablation of zone 1, interatrial conduction was slowed, but there was no
      block. After ablation of zone 2, conduction was unchanged. After ablation of both
      zones, complete block was observed in four animals, and there was left atrial
      quiescence. In the remaining nine animals, incomplete block was observed, with
      marked conduction slowing or block during sinus rhythm and pacing. Ablation did
      not adversely affect atrioventricular node conduction, nor did it facilitate
      sustenance of an atrial arrhythmia. Pathologic analysis revealed that complete
      interatrial conduction block was associated with confluent ablation of both
      targeted zones. CONCLUSIONS: Catheter ablation of the right atrial septum
      attenuated interatrial conduction without disturbing atrioventricular conduction.

PMID- 11527651
TI  - Cellular and humoral immune responses to heat shock protein 65 are both involved
      in promoting fatty-streak formation in LDL-receptor deficient mice.
AB  - OBJECTIVES: This study was designed to determine the role of cellular and humoral
      immune responses to heat shock protein 65 (HSP65) in murine atherosclerosis.
      BACKGROUND: Inflammatory processes appear to influence the progression of
      atherosclerosis. Immunization with HSP65 was previously shown to induce
      arteriosclerosis in rabbits and to enhance fatty-streak formation in mice.
      However, it has not been demonstrated directly whether HSP65-reactive antibodies
      and lymphocytes are separately capable of influencing lesion formation. METHODS:
      Low density lipoprotein-receptor deficient (LDL-RD) mice were immunized with
      HSP65 or control bovine serum albumin (BSA). Lymph-node cells, splenocytes and
      immunoglobulin G (IgG) were obtained from the immunized mice and transferred
      separately to six groups of syngenic LDL-RD mice. RESULTS: Adoptive transfer of
      HSP65-reactive lymph node cells increased fatty-streak formation in comparison
      with mice treated with BSA-primed cells. Similarly, transfer of splenocytes
      reactive with HSP65 led to enhanced fatty-streak generation compared with mice
      injected with BSA-sensitized splenocytes. Repeated intraperitoneal administration
      of IgG from serum of HSP65-immunized mice (every 10 days) enhanced fatty-streak
      formation in mice in comparison with their anti-BSA-IgG injected littermates.
      CONCLUSIONS: Antibodies and lymphocytes reactive to HSP65 promote fatty-streak
      formation in mice, providing direct evidence for the proatherogenic properties of
      cellular and humoral immunity to HSP65.

PMID- 11527653
TI  - ACCME standards for commercial support--time for a change?

PMID- 11527652
TI  - Gender-specific difference in cardiac ATP-sensitive K(+) channels.
AB  - OBJECTIVES: The main objective of this study was to establish whether gender
      regulates expression and/or properties of cardiac ATP-sensitive K(+) (K(ATP))
      channels. BACKGROUND: Recently, evidence has been provided that differing cardiac
      responses in males and females to metabolic stress may result from gender
      specific difference(s) in the efficiency of endogenous cardioprotective
      mechanism(s) such as K(ATP) channels. METHODS: A reverse transcription polymerase
      chain reaction (RT-PCR) using primers specific for Kir6.2, Kir6.1 and SUR2A
      subunits was performed on total RNA from guinea pig ventricular tissue. Western
      blotting using anti-Kir6.2 and anti-SUR2A antibodies was performed on cardiac
      membrane fraction. Whole-cell, single-channel electrophysiology and digital
      epifluorescent Ca(2+) imaging were performed on isolated guinea pig ventricular
      cardiomyocytes. RESULTS: The RT-PCR revealed higher levels of SUR2A, but not
      Kir6.1 and Kir6.2, messenger RNA in female tissue relative to male tissue, while
      much higher levels of both Kir6.2 and SUR2A proteins in cardiac membrane fraction
      in female tissue compared with male tissue were found. In both male and female
      tissue, pinacidil (100 microM), a K(ATP) channel opener, induced outward whole
      cell currents. The current density of the pinacidil-sensitive component was
      significantly higher in female tissue than it was in male tissue, while no
      differences in single K(ATP) channel properties between genders were observed.
      Ischemia-reperfusion challenge induced significant intracellular Ca(2+) loading
      in male, but not female, cardiomyocytes. To test the hypothesis that SUR2A
      expression is the limiting factor in K(ATP) channel formation, we took different
      volumes of Kir6.2 and SUR2A complementary DNA (cDNA) from the same cDNA pool and
      subjected them to PCR. In order to obtain a band having 50% of the maximal
      intensity, a volume of SUR2a cDNA approximately 20 times the volume of Kir6.2
      cDNA was required. CONCLUSIONS: This study has demonstrated that female tissue
      expresses higher levels of functional cardiac K(ATP) channels than male tissue
      due to the higher expression of the SUR2A subunit, which has an impact on cardiac
      response to ischemia-reperfusion challenge.

PMID- 11527654
TI  - The importance of the cardiologist.

PMID- 11527655
TI  - Low dietary zinc alters indices of copper function and status in postmenopausal
      women.
AB  - OBJECTIVES: To better define the relationship between dietary zinc and copper for
      humans so that sound recommendations for intakes of these elements can be made.
      METHODS: A study was conducted to ascertain the effect of moderately excessive
      and deficient intakes of zinc on copper metabolism and use in humans fed low and
      luxuriant amounts of copper. Twenty-one postmenopausal women housed in a
      metabolic unit completed the study as designed. After a 10-d equilibration period
      in which they were fed a diet providing 31.5 micromol (2 mg) Cu and 91.8 micromol
      (9 mg) Zn/8.4 MJ (2000 kcal), the women were divided into two groups. One group
      was fed a diet containing 15.7 micromol (1 mg) Cu/8.4 MJ (2000 kcal), and the
      other group was fed a diet containing 47.2 micromol (3 mg) Cu/8.4 MJ (2000 kcal).
      After equilibration, both groups were fed the basal diet providing 45.9 micromol
      (3 mg) Zn/8.4 MJ (2000 kcal) for 90 d; this was followed by another 10-d
      equilibration period before dietary zinc was increased to 811 micromol (53
      mg)/8.4 MJ (2000 kcal) for 90 d. RESULTS: The women were in positive copper
      balance only when the diet provided 47.2 micromol (3 mg) Cu and 811 micromol (53
      mg) Zn/d. Immunoreactive ceruloplasmin concentrations and platelet cytochrome-c
      oxidase activity on a platelet number basis were significantly lower and the
      ratio between enzymatic and immunoreactive ceruloplasmin was significantly higher
      during low dietary than during high dietary zinc intake. Serum cholesterol was
      higher in subjects fed 15.7 micromol (1 mg) Cu/d than in those fed 47.2 micromol
      (3 mg) Cu/d. Total and low-density lipoprotein cholesterol concentrations
      decreased with zinc supplementation. Whole-blood glutathione concentration and
      erythrocyte glutathione peroxidase activity were lower during high than during
      low dietary zinc intake. CONCLUSIONS: The findings indicate that an inadequate
      intake of zinc (45.9 micromol/d; 3 mg/d) was more effective than a moderately
      high intake of zinc (811 micromol/d; 53 mg/d) in inducing changes associated with
      a decreased copper status in postmenopausal women. Furthermore, the findings
      indicate that copper status indicators might be useful in evaluating changes in
      zinc status in humans, and an intake of 15.7 micromol (1 mg)/d of copper may be
      inadequate for postmenopausal women.

PMID- 11527656
TI  - Effect of vitamin and trace-element supplementation on cognitive function in
      elderly subjects.
AB  - OBJECTIVE: To determine whether supplementation with vitamins and trace elements
      in modest amounts influences cognitive function in apparently healthy, elderly
      subjects. METHODS: The study was designed as a randomized, double-blind, placebo
      controlled trial. Ninety-six, apparently healthy, independent men and women older
      than 65 y of age were recruited and randomized to receive a supplement of trace
      elements and vitamins or a placebo daily for 12 mo. Blood-nutrient levels were
      estimated at baseline and at the end of the study. The major outcome measure
      assessed was cognitive function consisting of immediate and long-term memory,
      abstract thinking, problem-solving ability, and attention. RESULTS: Eighty-six
      subjects completed the 1-y trial. The supplemented group showed a significant
      improvement in all cognitive tests (P < 0.001 to 0.05) except long-term memory
      recall (P > 0.1). Those whose blood-nutrient levels were below the reference
      standard showed lower responses on cognitive tests. There was no significant
      correlation between individual nutrient levels and performance on various
      cognitive function tests. CONCLUSIONS: Cognitive functions improved after oral
      supplementation with modest amounts of vitamins and trace elements. This has
      considerable clinical and public health significance. We recommend that such a
      supplement be provided to all elderly subjects because it should significantly
      improve cognition and thus quality of life and the ability to perform activities
      of daily living. Such a nutritional approach may delay the onset of Alzheimer's
      disease.

PMID- 11527657
TI  - Heritability of diurnal changes in food intake in free-living humans.
AB  - OBJECTIVES: The time of day of meal ingestion, the number of people present at
      the meal, the subjective state of hunger, and the estimated before-meal contents
      in the stomach have been established as influences on the amount eaten in a meal,
      and this influence has been shown to be heritable. Because these factors
      intercorrelate, the possibility that the calculated heritabilities for some of
      these variables could result indirectly from their convariation with one of the
      other heritable variables was assessed. METHODS: The independence of the
      heritability of the influence of these four factors was investigated with 110
      identical and 102 fraternal same-sex and 53 fraternal mixed-sex adult twin pairs
      who were paid to maintain 7-d food intake diaries. From the diary reports, the
      meal sizes were calculated and subjected to multiple regression analysis using
      the estimated before-meal stomach contents, the reported number of other people
      present, the subjective hunger ratings, and the time of day of the meal as
      predictors. Linear structural modeling was applied to the beta coefficients from
      the multiple regression to investigate whether the heritability of the influences
      of these four variables was independent. RESULTS: Significant genetic effects
      were found for the beta coefficients for all four variables, indicating that the
      heritability of their relationship with intake is to some extent heritable.
      CONCLUSIONS: These results suggest that the influences of multiple factors on
      intake are influenced by the genes and become part of the total package of
      genetically determined physiologic, sociocultural, and psychological processes
      that regulate energy balance.

PMID- 11527658
TI  - Folate supplementation prevents plasma homocysteine increase after fenofibrate
      therapy.
AB  - BACKGROUND: Homocysteine is associated with an increased risk of atherosclerosis.
      The administration of fibrates has been reported to significantly increase plasma
      homocysteine levels, a potentially adverse effect of fibrates. We investigated
      the hypothesis that concomitant treatment with fenofibrate and folic acid leads
      to a smaller increase in plasma total homocysteine levels than treatment with
      fenofibrate alone. METHODS: A randomized, open-label study compared the effect of
      micronized fenofibrate (200 mg daily) alone versus fenofibrate plus folic acid
      (10 mg every other day) on plasma homocysteine levels. Twenty-two patients with
      mixed hyperlipidemia participated. The 9-wk treatment period was preceded by a 4
      wk wash-out period without hypolipidemic drugs. RESULTS: In patients treated with
      fenofibrate only, plasma homocysteine levels increased by 6.85 +/- 5.23
      micromol/L (from 12.27 +/- 3.15 to 19.13 +/- 7.20 micromol/L); in patients
      treated with fenofibrate and folic acid, plasma homocysteine levels increased by
      2.01 +/- 2.88 micromol/L (from 10.14 +/- 2.32 to 12.15 +/- 3.08 micromol/L). The
      difference in the homocysteine increase between the two groups was statistically
      significant at P = 0.014. CONCLUSIONS: Folic acid supplementation in patients
      treated with fenofibrate significantly reduced the increase in plasma
      homocysteine levels. More studies are needed to clarify whether amelioration of
      this side effect increases the clinical benefit of fibrates.

PMID- 11527660
TI  - Norepinephrine-induced glycerol release from adipose tissue: influence of age and
      body mass index in obese people.

PMID- 11527659
TI  - Nutrition disorders and immunologic parameters: study of the thymus in growing
      rats.
AB  - OBJECTIVES: We studied the effect of a low-quality dietary protein on cellular
      proliferation and maturation in the thymus of growing rats over time. METHODS:
      After weaning Wistar rats were fed a diet containing 6.5 g/100 g of corn flour
      for 6, 10, 18, and 45 d (M groups). For comparison, other rats were fed a diet
      containing 6.5 g/100 g of casein (Cas groups), and well-nourished age-matched
      control rats were fed a commercial laboratory diet (C groups). Food intake, body
      weight, thymus weight, total number of thymocytes, and the percentages of CD43(+)
      and Thy1(+) thymocyte phenotypic antigen determinants were measured. RESULTS: M
      versus Cas and C groups showed significant differences (P < 0.01) in body and
      thymus weights after 6 d of feeding, and the total number of thymocytes and the
      percentages of CD43(+) and Thy1(+) were significantly lower after 10 d of
      feeding. The results indicated that consuming a cereal diet for short or long
      periods causes thymus atrophy in growing rats, with significant reductions in the
      total number of T-cells concomitant with increases in the number of immature
      thymocytes. CONCLUSIONS: The data showed that, in addition to low-protein
      concentration, low-quality dietary protein is a limiting factor in certain steps
      of cellular intrathymic pathways, probably related to the requirement of specific
      amino acids for optimal immune response.

PMID- 11527661
TI  - Circadian rhythmicity of whole-blood glutathione in healthy subjects.
AB  - OBJECTIVES: Physiologic rhythms of antioxidants have been the subject of
      considerable interest in recent years. Physiologically, it is known that 24-h
      variability in whole-blood glutathione (GSH) could depend on various factors,
      such as meal composition, protein dietary content, meal-related hormonal
      modifications, and stress. Experiments were conducted to determine if the
      circadian variations previously observed in hepatic concentrations of reduced
      glutathione in animals also occurred in healthy volunteers. METHODS: The
      circadian periodicity of whole-blood glutathione was explored. All parameters
      were measured enzymatically at 4-h intervals over a 24-h period. RESULTS:
      Circadian rhythms were not found. The rhythms peak for glutathione content
      occurred at 9 h with a small peak at 21 h. The nadir occurred at 17 h and 1 h.
      CONCLUSION: These data show that despite this wide distribution of glutathione
      throughout the day we could not find any significant intertime variability.

PMID- 11527662
TI  - Zinc and copper: evidence for interdependence, not antagonism.

PMID- 11527663
TI  - Breast feeding, infant formulae, and oral tolerance.

PMID- 11527664
TI  - Folic-acid-mediated inhibition of human colon-cancer cell growth.

PMID- 11527665
TI  - Folate homeostasis and antiproliferative activity of folates and antifolates.

PMID- 11527666
TI  - Is it worthwhile to try different coenzymatic forms of folate in future
      chemoprevention trials?

PMID- 11527667
TI  - Energy regulation in inflammation-induced anorexia: implications for treatment.

PMID- 11527668
TI  - The balance between omega-6 and omega-3 fatty acids and the risk of coronary
      heart disease.

PMID- 11527670
TI  - Malnutrition in the critically ill.

PMID- 11527671
TI  - Irreversible intestinal failure, nutrition support, and small bowel
      transplantation.
AB  - OBJECTIVES: Prolonged total parenteral nutrition (TPN) is a palliative but life
      saving treatment for patients with irreversible intestinal failure (IIF). During
      the past few years, intestinal transplantation (ITx) has become the most
      realistic alternative to TPN. METHODS: We identified potential candidates for
      ITx, reported clinical data of the international Intestinal Transplant Registry,
      and analyzed the intestinal function after transplantation and the common
      nutrition strategies usually adopted in the recipients. RESULTS: At present,
      candidates for ITx are patients with IIF who develop a life-threatening
      complication during TPN treatment. During the past few years, clinical results
      have improved mainly in relation to the progress in immunosuppression, but
      prevention of the acute cellular rejection (ACR) is still the key point. ACR,
      high doses of immunosuppressant drugs, and intestinal bacterial translocation can
      exacerbate intestinal malabsorption and sustain systemic complications such as
      sepsis and multiorgan failure. Early enteral alimentation is started after ITx
      and gradually increased. To prevent dehydration and malnutrition caused by
      persistent diarrhea, parenteral nutrition is frequently maintained for 1 to 2 mo.
      More than 66% of long-term recipients become nutritionally independent of TPN.
      CONCLUSIONS: ITx is now a life-saving option for patients with IIF and severe
      complications from TPN. Clinical and nutritional management of the recipients is
      a complex procedure and requires a great deal of expertise. After transplantation
      most adults maintain adequate nutrition status and children have normal growth.
      Multiple episodes of ACR, early and persistent dehydration, and malabsorption are
      still common problems that influence the recipient's quality of life.

PMID- 11527672
TI  - Cancer cachexia and its treatment with fish-oil-enriched nutritional
      supplementation.
AB  - OBJECTIVE: Cachexia is a common condition affecting those with advanced cancer.
      This review explores mechanisms of cachexia and possible treatments devised with
      these mechanisms in mind. METHODS: Selective review of the relevant scientific
      literature was performed with particular emphasis on studies performed by our
      group over the past 10 y involving patients with advanced pancreatic cancer.
      RESULTS: Cancer cachexia adversely affects patient quality of life and survival.
      It is characterized by a lack of a normal anabolic response to the provision of
      apparently adequate nutrition. It appears to result from a persistent response to
      illness stimulated by the cancer resulting in a proinflammatory cytokine and
      catabolic hormonal environment. Interventions that ignore this inflammatory
      milieu have had little success. More promising interventions have a broad
      antiinflammatory component such as nonsteroidal antiinflammatory drugs or fish
      oil. Preliminary studies of a combination of fish oil as an antiinflammatory
      agent with nutritional supplementation show promise in reversing weight loss with
      apparent gains in lean tissue and performance status in association with
      normalization of the metabolic environment in patients with advanced pancreatic
      cancer. CONCLUSIONS: Cancer cachexia produces a metabolic environment that
      prevents the appropriate use of supplied nutrition. Antiinflammatory agents such
      as fish oil in combination with nutritional supplementation may reverse aspects
      of cachexia.

PMID- 11527673
TI  - Metabolic and nutritional disorders in cardiac cachexia.
AB  - Cardiac cachexia is divided into two types, i.e., the classic type, which occurs
      in patients with severe heart failure, and the nosocomial type, which develops in
      the postoperative state. Cardiac cachexia is due both to a decrease in nutrient
      intake (anorexia, malabsorption) and to specific metabolic alterations
      (hypercatabolism with increased energy expenditure, response to hypoxia,
      inflammatory status, etc). Among the various mechanisms involved in the
      pathogenesis of cachexia, cellular hypoxia has long been recognized. The chronic
      activation of the endogenous neurohormonal system is another specific feature of
      such patients; a striking relationship was found between cardiac cachexia and
      hormonal levels which correlate better than the classical parameters of cardiac
      failure severity. Finally, inflammatory syndrome has been known to occur
      frequently in patients with cardiac cachexia. Several studies have shown that
      tumor necrosis factor-alpha was significantly increased in cachectic patients and
      that chronic activation of the systemic immune response might be a common and
      unifying factor.

PMID- 11527674
TI  - Nutritional assessment in various stages of liver cirrhosis.
AB  - OBJECTIVES: The aims of this study were to determine the prevalence of protein
      calorie malnutrition, characteristics, and clinical importance of nutrition
      disorders in patients with liver cirrhosis according to severity of disease.
      METHODS: Nutrition assessments such as subjective global assessment,
      anthropometric and biochemical measurements, immunocompentency, thiamin and
      riboflavin status in 60 patients with cirrhosis (33 male and 27 female) were
      recorded between June 1999 and December 1999 at an outpatient clinic at
      Ramathibodi Hospital, Bangkok, Thailand. The origin of liver disease was alcohol
      related in 50% of patients. Child-Pugh criteria were used to establish the
      severity of liver disease. RESULTS: In terms of energy malnutrition, 13.3% of
      patients had ideal body weights below 90% and 11.7% had body mass indexes below
      18.5 kg/m(2). Protein malnutrition (low albumin) and immunoincompetence (abnormal
      response to skin tests) were found much more frequently (45% and 22%) than energy
      malnutrition. Patients with alcoholic cirrhosis had ascites (P < 0.05) and
      hepatic encephalopathy (P < 0.001) more frequently and less triceps skinfold
      thickness than those with non-alcoholic cirrhosis. Subjective global assessment
      and serum proteins correlated with the degree of liver-function impairment, but
      immunologic tests correlated inversely in cirrhosis patients. Mean values for
      creatinine-height index, hemoglobin, cholesterol, and complement C4 showed
      significant decreases in severe liver failure (Child-Pugh class C) only in
      patients with alcoholic cirrhosis (P < 0.05). Malnutrition was correlated with
      the clinical severity of liver disease. CONCLUSIONS: The study showed that
      protein-energy malnutrition is a common complication of liver cirrhosis.
      Nutritional disorders appeared to be related to the degree of liver injury and
      the etiology of nutritional disorders. Nutritional disorders were more severe
      with alcoholic cirrhosis than with non-alcoholic cirrhosis.

PMID- 11527675
TI  - Glutamine supplementation in cancer patients.
AB  - OBJECTIVES: Three series of studies investigated whether 1) glutamine deficiency
      occurs in tumor-bearing rats, 2) glutamine supplementation improves protein
      metabolism during chemotherapy in tumor-bearing rats, and 3) oral glutamine
      supplement improves systemic immune and gut-barrier function in patients with
      esophageal cancer receiving radiochemotherapy. METHODS: In the animal studies,
      AH109A hepatoma cells or Yoshida sarcoma cells were inoculated into male Donryu
      rats to induce tumors. Glutamine production was measured by U-14C-glutamine
      infusion and the conversion of arginine to glutamine was measured by infusion of
      U-14C-arginine. The effect of glutamine on protein metabolism was investigated by
      1-14C-leucine infusion. In the clinical study, 13 patients with esophageal cancer
      were randomized into two groups, control and glutamine supplemented (30 g/d), for
      4 wk. RESULTS: Glutamine levels in plasma and skeletal muscle were decreased in
      tumor-bearing rats, although glutamine production and the conversion of arginine
      to glutamine were increased. Glutamine-supplemented total parenteral nutrition
      reduced whole-body protein breakdown rate during chemotherapy in tumor-bearing
      rats. Oral supplementation of glutamine to the patients with esophageal cancer
      enhanced lymphocyte mitogenic function and reduced permeability of the gut during
      radiochemotherapy. CONCLUSIONS: Glutamine depletion in host tissues occurs in
      tumor-bearing rats. Glutamine supplementation can attenuate loss of protein in
      the muscle in tumor-bearing animals and protect immune and gut-barrier function
      during radiochemotherapy in patients with advanced cancer.

PMID- 11527676
TI  - Cancer: impact of nutrition intervention outcome--nutrition issues for patients.
AB  - OBJECTIVE: We examined nutritional issues, assessment, and intervention
      strategies for patients with cancer. METHODS: Reviews of practice guidelines and
      published reports were used to identify nutritional issues and strategies that
      can benefit patients with cancer. RESULTS: Assessment tools such as the Patient
      Generated Subjective Global Assessment are useful in terms of identifying
      patients with nutrition issues and guiding intervention. However, quality of life
      and other measures should also be considered. There is a need for early and
      ongoing nutrition interventions. CONCLUSIONS: Encourage patients to try a new
      food or supplement on days when they are not receiving chemotherapy or radiation
      therapy because it may result in better tolerance. Screen patients to determine
      their nutritional status. Closely monitor changes in weight, food intake, and
      symptoms such as nausea and vomiting. Refer to a registered dietitian for a
      complete nutrition assessment and individualized counseling.

PMID- 11527677
TI  - Parenteral nutrition support after bone marrow transplantation: comparison of
      total and partial parenteral nutrition during the early posttransplantation
      period.
AB  - OBJECTIVE: Bone marrow transplantation (BMT) usually is indicated if the
      patient's malignant disease involves the marrow or if hazard to the normal marrow
      is the limiting factor in the aggressive treatment of disease. The success of BMT
      depends on a complete team with all the resources needed to ensure optimal
      results. Aggressive nutrition support after BMT is very important. Adequate
      parenteral nutrition, total (TPN) or partial, followed by enteral nutrition
      according to the patient's gastrointestinal function is the important principle.
      METHODS: Between 1996 and 2000, 60 patients, 46 male and 14 female, received BMT
      in Chang Gung Memorial Hospital. Their ages ranged from 6 to 54 y. Standard TPN
      was used in 40 patients after BMT, and partial parenteral nutrition was used in
      the remaining 20 patients. TPN was enriched with branched-chain amino acids
      (BCAA) when the patient's liver functions were impaired, and cyclic TPN was
      shifted when the patient's liver functions persistently deteriorated. RESULTS:
      Most patients improved their nutrition status and increased their body weights,
      especially those receiving TPN. The patients receiving partial parenteral
      nutrition decreased their visceral proteins significantly during the course of
      parenteral nutrition. The BCAA-TPN can maintain a patient's visceral protein
      better than standard TPN. Only two patients expired because of graft rejection
      and sepsis; their body weights and nutrition status showed deterioration despite
      aggressive nutrition support. CONCLUSIONS: We conclude that the nutrition support
      for patients with BMT is related to the success of marrow transplantation.
      Parenteral nutrition support, especially with TPN, is important because of
      frequent gastrointestinal dysfunction during the posttransplantational period,
      and it is better at maintaining the nutrition status and body weights of patients
      after BMT. An oral diet can be resumed after the patient's gastrointestinal
      function has improved and it can be tolerated.

PMID- 11527678
TI  - Decisions for enteral access in the intensive care unit.
AB  - When making decisions regarding nutrition support, many factors must be
      considered before committing a patient to receive parenteral or enteral
      nutrition. Parenteral nutrition (PN) is more expensive and technically more
      difficult to administer than enteral nutrition (EN). The charge for PN can range
      from US 200 dollars to 1000 dollars per day, where a standard hospital diet or
      enteral tube feedings might cost less than US 25 dollars/d. PN is also associated
      with a much higher incidence of biochemical complications such as hyperglycemia
      and other electrolyte abnormalities and catheter-related complications such as
      infection, thrombosis, or pneumothorax. For many years PN was preferred to EN
      because it was believed to be unwise to feed a critically ill patient into the
      gut. It has now been shown in multiple studies that it is not only feasible to
      feed critically ill patients early, but also it may be immunologically
      advantageous to feed enterally. The cost effectiveness of the nutrition support
      team approach to monitoring PN and EN should not be underestimated by hospital
      administrators. If enteral therapy can be instituted, significant patient-care
      cost savings may be realized. This presentation will discuss decisions that must
      be addressed in the intensive care unit. With more physician education, protocols
      can be designed to provide the most advantageous use of nutrition support for the
      benefit of the hospitalized patient.

PMID- 11527679
TI  - A trawl through the current nutrition literature.

PMID- 11527680
TI  - Glutathione-nutritional and pharmacologic viewpoints: Part IV.

PMID- 11527681
TI  - Nutrition assessment.

PMID- 11527682
TI  - A future for hyperthermia in cancer treatment?

PMID- 11527683
TI  - Cremophor EL: the drawbacks and advantages of vehicle selection for drug
      formulation.
AB  - Cremophor EL (CrEL) is a formulation vehicle used for various poorly-water
      soluble drugs, including the anticancer agent paclitaxel (Taxol). In contrast to
      earlier reports, CrEL is not an inert vehicle, but exerts a range of biological
      effects, some of which have important clinical implications. Its use has been
      associated with severe anaphylactoid hypersensitivity reactions, hyperlipidaemia,
      abnormal lipoprotein patterns, aggregation of erythrocytes and peripheral
      neuropathy. The pharmacokinetic behaviour of CrEL is dose-independent, although
      its clearance is highly influenced by duration of the infusion. This is
      particularly important since CrEL can affect the disposition of various drugs by
      changing the unbound drug concentration through micellar encapsulation. In
      addition, it has been shown that CrEL, as an integral component of paclitaxel
      chemotherapy, modifies the toxicity profile of certain anticancer agents given
      concomitantly, by mechanisms other than kinetic interference. A clear
      understanding of the biological and pharmacological role of CrEL is essential to
      help oncologists avoid side-effects associated with the use of paclitaxel or
      other agents using this vehicle. With the present development of various new
      anticancer agents, it is recommended that alternative formulation approaches
      should be pursued to allow a better control of the toxicity of the treatment and
      the pharmacological interactions related to the use of CrEL.

PMID- 11527684
TI  - Neoadjuvant chemotherapy combined with regional hyperthermia (RHT) for locally
      advanced primary or recurrent high-risk adult soft-tissue sarcomas (STS) of
      adults: long-term results of a phase II study.
AB  - In this phase II study, activity and safety of neoadjuvant regional hyperthermia
      (RHT) combined with chemotherapy was investigated in 59 patients with primary
      advanced or recurrent high-risk soft-tissue sarcoma (STS). Patients received four
      EIA cycles consisting of etoposide, ifosfamide and doxorubicin combined with RHT
      followed by surgical resection and adjuvant treatment. The overall objective
      response (OR) rate was 17%, with one complete (2%) and eight partial (15%)
      responses. In addition, 13 minor responses (25%) were seen. At time of surgery,
      complete necrosis (pCR) occurred in 6 patients and >75% necrosis (favourable
      histological response (FHR)) in 12 patients. At the completion of protocol
      treatment, 36 patients were rendered disease-free which was significantly
      associated with the initial radiographic and/or pathological tumour response
      (P=0.004). Treatment-related toxicity was acceptable overall. At a medium follow
      up of 82 months, local treatment failure occurred in 33 patients, median overall
      survival (OS) was 52 months, and the 5-year survival rate was 49% (95% confidence
      interval (CI): 36-61%). OS which did not differ for extremity versus non
      extremity STS (P=0.21) was better for patients responding to EIA combined with
      RHT (P<0.01).

PMID- 11527686
TI  - Predicting cancer-associated anaemia in patients receiving non-platinum
      chemotherapy: results of a retrospective survey.
AB  - A 2-year retrospective chart survey of 1064 patients with colorectal, breast,
      lung or ovarian cancer, Hodgkin's disease, or non-Hodgkin's lymphoma was
      conducted at 24 centres in France to determine the prevalence of anaemia
      (haemoglobin (Hb) levels < or = 120 g/l) and need for transfusion in patients who
      received non-platinum-based chemotherapy for more than three cycles or 3 months.
      Baseline Hb levels documented anaemia in 37.1% of patients (all tumour types). By
      cycle 3, the prevalence of anemia increased to 54.1% of patients and remained
      over 50% at cycle 4. At some time during chemotherapy 14.5% of patients were
      transfused. Predictive risk factors for anaemia requiring transfusion included
      low baseline Hb, decrease in Hb during the first month of chemotherapy, primary
      tumour site, prior blood transfusions and duration of chemotherapy. By early
      identification of patients at the highest risk of developing anaemia,
      interventions such as epoetin alfa can be employed to reduce or eliminate the
      need for transfusions.

PMID- 11527685
TI  - Treatment of primary, recurrent or inadequately resected high-risk soft-tissue
      sarcomas (STS) of adults: results of a phase II pilot study (RHT-95) of
      neoadjuvant chemotherapy combined with regional hyperthermia.
AB  - The efficacy of thermochemotherapy in adult patients with primary, recurrent or
      inadequately resected non-metastatic high-risk soft-tissue sarcomas (STS) was
      assessed. 54 patients were prospectively treated with four cycles of etoposide,
      ifosfamide and doxorubicin (EIA) combined with regional hyperthermia (RHT)
      followed by surgery, another four cycles of EIA without RHT and external beam
      radiation. The objective response rate was 16% and at a median follow-up time of
      57 months, the 4-year estimated rates of local failure-free survival (LFFS),
      distant metastasis-free survival (DMFS), event-free survival (EFS) and overall
      survival (OS) were 59% (95% confidence interval (CI) 45-73%), 59% (95% CI 44
      73%), 26% (95% CI 14-38%) and 40% (95% CI 27-53%), respectively. OS was in favour
      of patients responding to neoadjuvant treatment (P=0.073). In comparison to a
      preceding phase II study including pre- and postsurgical thermochemotherapy (RHT
      91), at a 4-year follow-up the RHT-95 study cohort showed an inferior LFFS rate
      (P=0.027), but this did not affect DMFS (P=0.558) or OS (P=0.126). Hence,
      postsurgical thermochemotherapy seems critical for local tumour control without
      affecting survival.

PMID- 11527687
TI  - Phase II study of mitomycin-C and cisplatin in disseminated, squamous cell
      carcinoma of the uterine cervix. A European Organization for Research and
      Treatment of Cancer (EORTC) Gynecological Cancer Group study.
AB  - The aim of this study was to investigate the tumour response rate and toxicity of
      a combination chemotherapy consisting of mitomycin-C and cisplatin in patients
      with disseminated squamous-cell carcinoma of the uterine cervix. Chemotherapy
      consisted of mitomycin, 6 mg/m(2) intravenously (i.v.), and cisplatin, 50 mg/m(2)
      given i.v., both administered on day 1 of each cycle. The regimen was repeated at
      4-weekly intervals. Mitomycin-C/cisplatin were used to treat 33 evaluable
      patients aged 29-67 years (median: 50 years). All patients except 1 had
      previously been treated with either surgery, radiation or both. At the initiation
      of chemotherapy, 8 patients had loco-regional and disseminated disease and 25
      women had only distant metastases. The overall response rate was 42% (95%
      confidence interval (CI): 26-61%). Five complete and nine partial responses were
      observed with a median duration of response of 7.9 months (95% CI: 3.7-23.5
      months). 9 patients had stable disease and 10 developed progressive disease
      during mitomycin-C/cisplatin-treatment. World Health Organization (WHO) grade
      III/IV side-effects were documented in 15 women, of whom 10 had gastro-intestinal
      toxicity, 3 had haematological toxicity, 1 had alopecia and 1 developed an
      allergic reaction to cisplatin. There were neither drug-related deaths nor severe
      or irreversible renal or hepatic dysfunction or peripheral neuropathy. The median
      progression-free survival was 5.0 months (95% CI: 3.6-6.2 months) for all
      patients and 10.5 months (95% CI: 6.2-15.2 months) for the responders. The median
      overall survival was 11.2 months (95% CI: 6.5-18.4 months).The mitomycin
      C/cisplatin combination showed antitumour activity in the treatment of advanced
      or recurrent squamous-cell carcinoma of the uterine cervix. The regimen was well
      tolerated and could be administered on an outpatient basis.

PMID- 11527688
TI  - Serum adhesion molecules and interleukin-2 receptor as markers of tumour load and
      prognosis in advanced cutaneous melanoma.
AB  - Cell adhesion molecules are cell surface glycoproteins that may act as mediators
      in the metastatic process. Soluble interleukin-2 receptor (sIL-2R) is an
      immunological marker that may also serve as an indicator of tumour progression.
      Normal and neoplastic cells are capable of releasing these molecules into
      circulation. We evaluated the association between pretreatment serum levels of
      soluble intercellular adhesion molecule 1 (sICAM-1), vascular cell adhesion
      molecule 1 (sVCAM-1) and sIL-2R and metastases and survival in 50 patients with
      advanced melanoma. The patients with liver and/or bone metastases had
      significantly higher sICAM-1 levels than those with soft tissue and/or lung
      involvement (P=0.002). In addition, there was a trend towards higher sIL-2R
      levels in patients with more metastatic sites (P=0.07). In univariate analysis,
      the number of metastatic sites (P=0.0001, odds ratio (OR) 3.0, 95% confidence
      interval (CI): 1.7-5.3), the metastatic site (P=0.01, OR 2.3, 95% CI: 1.2-4.4)
      and the levels of sICAM-1 (P=0.011, OR 2.5, 95% CI: 1.2-5.0), sVCAM-1 (P=0.036,
      OR 2.1, 95% CI: 1.0-4.3) and sIL-2R (P=0.0016, OR 3.0, 95% CI: 1.5-6.0) were
      found to be statistically significant prognostic factors for survival. In
      multivariate analysis, the number of metastatic sites was the dominant prognostic
      indicator. After it was excluded from the analysis, the sIL-2R level and the
      metastatic site were found to be significant. It can be concluded, that high
      sICAM-1 levels suggest liver metastases and sIL-2R seems to serve as a marker of
      tumour load in metastatic melanoma. Furthermore, the sIL-2R level appears to add
      to clinical data predicting the patient's outcome.

PMID- 11527689
TI  - Proliferation kinetics and prognosis in gastric cancer after resection.
AB  - The influence of proliferation and proliferation kinetics on prognosis in gastric
      cancer after complete resection are controversial. In a prospective study we
      investigated the tumour specimens of 111 patients after resection of gastric
      cancer, who received 200 mg intravenous (i.v.) bromodeoxyuridine (BrdU) pre
      operatively. The following biological parameters were analysed in the tumour
      tissue using flow-cytometry: DNA ploidy, proportion of S-phase cells, BrdU
      labelling index (LI), DNA synthesis time (T(s)), potential tumour doubling time
      (T(pot)), proliferating cell nuclear antigen (PCNA) and Ki-67 LI. The median
      follow-up time was 40 months (range 19-62 months). Besides the established
      pathohistological prognostic factors, univariate analysis revealed a prognostic
      influence on survival for BrdU LI, T(pot) and the proportion of S-phase cells. By
      multivariate Cox analysis of the completely resected cases, only tumour stage and
      T(pot) had a significant, independent influence on survival. By classification
      and regression trees (CART) analysis, resection status, tumour stage and T(pot)
      defined risk groups with significantly different outcomes. A short T(pot) was a
      predictor of better survival in stage I, II and IIIA tumours. Ploidy and the
      other investigated proliferation-related parameters failed to demonstrate any
      influence on prognosis after resection of gastric cancer.

PMID- 11527690
TI  - UFT and leucovorin in first-line chemotherapy for patients with metastatic
      gastric cancer. An Early Clinical Studies Group (ECSG)/European Organization for
      Research Treatment of Cancer (EORTC) phase II trial.
AB  - A phase II study was performed to evaluate 1-(2-tetrahydrofuryl)-5-fluorouracil
      and uracil (UFT) and leucovorin as first-line chemotherapy in European patients
      with advanced gastric cancer. From 38 patients, 25 were evaluable for response
      and 36 for toxicity. Patients received UFT at 300 mg/m(2)/day for 28 days, every
      35 days and leucovorin at 90 mg/day on an identical schedule. Overall response
      rate was 10.5% (95% confidence interval (CI): 3.7-22.5%) in intent-to-treat
      analysis and 16% (95% CI: 5.7-33%) in evaluable patients. Grade 3-4 common
      toxicity criteria (CTC) toxicities were diarrhoea (28%; 10/36), nausea (11%;
      4/36), vomiting (8%; 3/36) and asthenia (11%; 4/36). 23 patients in 44% (42/96)
      of the courses had to skip days of treatment due to toxicity or to non
      compliance. In conclusion, UFT+leucovorin has a definitive, but low, efficacy in
      advanced gastric cancer patients. Toxicities were mainly gastrointestinal and
      treatment needs to be withheld if grade 2 diarrhoea occurs.

PMID- 11527691
TI  - Indwelling lines and nutrition.

PMID- 11527693
TI  - Cancer survival increases in Europe, but international differences remain wide.
AB  - The EUROCARE project analysed cancer survival data from 45 population-based
      cancer registries in 17 European countries, revealing wide international
      differences in cancer survival. We calculated 5-year relative survival for
      1836287 patients diagnosed with one of 13 cancers during the period 1978-1989.
      The data, from 20 cancer registries in 13 countries, were grouped into four
      regions: Finland, Sweden, Iceland (Northern Europe); Denmark, England and
      Scotland (UK and Denmark); France, The Netherlands, Germany, Italy and
      Switzerland (Western Europe); Estonia and Poland (Eastern Europe), and broken
      down into four periods (1978-1980, 1981-1983, 1984-1986, 1987-1989). For each
      cancer, mean European and regional survival was estimated as the weighted mean of
      5-year relative survival in each country. Survival increased with time for all
      tumours, particularly for cancers of testis (12% increase, i.e. from 79.9 to
      91.9%), breast, large bowel, skin melanoma (approximately 9-10%), and lymphomas
      (approximately 7%). For most solid tumours, survival was highest in Northern
      Europe and lowest in Eastern Europe, and also low in the UK and Denmark. Regional
      variation was less marked for the lymphomas. Survival improved more in Western
      than Northern Europe, and the differences between these regions fell for bowel
      cancer (from 8.0% for those diagnosed in 1978-1980 to 2% for those diagnosed in
      1987-1989), breast cancer (from 7.4% to 3.9%), skin melanoma (from 13.4% to
      11.0%) and Hodgkin's disease (from 7.2 to 0.6%). For potentially curable
      malignancies such as Hodgkin's disease, large bowel, breast and testicular
      cancers, there were substantial increases in survival, suggesting an earlier
      diagnosis and more effective treatment. The persisting regional differences
      suggest there are corresponding differences in the availability of diagnostic and
      therapeutic facilities, and in the effectiveness of healthcare systems.

PMID- 11527694
TI  - The incidence of breast cancer from screening women according to predicted family
      history risk: Does annual clinical examination add to mammography?
AB  - In breast cancer, mutations of predisposition genes such as BRCA-1/2 and other
      genes as yet uncharacterised are manifest in up to 10% of cases. Although the
      prior probability of the presence of a breast cancer predisposing gene can be
      calculated for individual women, there is no published evidence to justify
      predicted risk as a selection criteria for screening. This study aims to define
      which patient groups with a significant family history should be screened, and
      whether clinical examination is necessary in addition to mammography. The Claus
      model was used to predict breast cancer risk in women with a family history.
      Women were divided into two groups according to their predicted risk: group I
      consisted of women at standard risk (lifetime risk less than 1:6) and group II
      with moderate/high risk (lifetime risk greater than or equal to 1:6). Women were
      cancer-free at the point of entry, and screening consisted of annual clinical
      examination and mammography from the age of 35 years. This study consisted of
      1500 women in group I and 1078 in group II. The period of observation was 5902.0
      and 4327.8 women years, respectively. A total of 31 cancers were detected, 12 in
      group I and 19 in group II. The median age at diagnosis in group II was 45 years
      (range 26-66 years) compared with 54.5 years (range 38-63 years) in group I
      (P=0.03). The relative risk of developing breast cancer in group II was 2.6 (95%
      confidence interval (CI) 1.2-5.8). When compared with breast cancer incidence in
      the normal population, the standardised incidence ratio in group II was
      significantly higher at 2.8 (95% CI: 1.7-4.2). The standardised incidence ratio
      of women in group I was similar to that of the general population (1.1 (95% CI:
      0.6-1.8)). A total of 26/31 (84%) cancers detected were palpable, of which 14
      (54%) were not visible on mammography. Approximately one-third of all palpable
      cancers were detected at routine follow-up. Mammography correctly identified
      17/31 cancers (55%), but 29% of these were not palpable. Family history screening
      programmes are effective and women should be selected for screening according to
      predicted risk. The younger age of diagnosis in group II justifies screening from
      an earlier age using both annual clinical examination and mammography.

PMID- 11527695
TI  - Long-term prognosis of gastric cancer in a European country: a population-based
      study in Florence (Italy). 10-year survival of cases diagnosed in 1985-1987.
AB  - This paper analysed, in a population-based series of 1976 gastric cancers
      diagnosed in Florence (Italy), from 1985 to 1987, the relationship between
      prognostic variables (demographic, clinical and pathological) and 10-year
      survival rates. Gastric cancer was mostly detected in elderly patients (mean age:
      70.5 years) and at advanced stages (i.e. approximately 50% of the patients could
      not undergo radical surgery). Ten-year observed survival was 12.1% (95%
      confidence interval (CI): 10.6-13.6%) for the whole series and 20.8% (95% CI:
      18.3-23.3%) for resected cases; relative survival was, respectively, 20.9% (95%
      CI: 18.4-23.4%) and 32.0% (95% CI: 28.1-35.9%). Ten-year relative survival was
      86% for stage IA (95% CI: 73-99%) and 67% for stage IB (95% CI: 52-82%).
      Multivariate analysis showed a significantly better prognosis in females and a
      significantly worse prognosis in patients aged 65 years or more (reference: < or
      = 59 years). In addition, an independent prognostic effect was observed for pT in
      the resected cases (reference: pT3; pT1: RR = 0.47, 95% CI: 0.34-0.64; pT2 =
      0.71, 95% CI: 0.58-0.87; pT4: RR = 2.02, 95% CI: 1.49-2.75), pN (reference: pN0;
      pN1: RR = 2.13, 95% CI: 1.70-2.68; pN2-3: RR = 3.14, 95% CI: 2.42-4.07; pN+ no.
      nodes involved unspecified: RR = 4.26, 95% CI: 3.11-5.83) and surgical margin
      involvement (reference: not involved; involved: RR = 1.36, 95% CI: 1.08-1.72). In
      addition, the stage, after adjustment for age, gender and surgical margin
      involvement, showed a strong independent prognostic value (reference: stage II;
      IA: RR=0.37, 95% CI: 0.25-0.57; IB: RR=0.70, 95% CI: 0.50-0.98; IIIA: RR = 1.80,
      95% CI: 1.40-2.33; IIIB: RR = 2.82, 95% CI: 2.14-3.72; IV: RR = 3.29, 95% CI:
      2.36-4.59). In conclusion, on the basis of a large population-based series, our
      results confirm the prognostic effect on long-term gastric cancer survival of
      pathological and demographic variables. In addition, the study shows that Italy
      had a relatively good, long-term survival when diagnosis was performed at early
      stages. However, only a few cases were diagnosed at stages when cure by radical
      surgery is more likely (i.e. stage I accounted for approximately 20% of the
      resected cases and less than 10% of all incident cases).

PMID- 11527696
TI  - Thymidylate synthase (TS) and ribonucleotide reductase (RNR) may be involved in
      acquired resistance to 5-fluorouracil (5-FU) in human cancer xenografts in vivo.
AB  - A human tumour sub-line resistant to 5-fluorouracil (5-FU) was established by
      once a day and every 5, with at least 50 administrations of 5-FU to KM12C human
      colorectal xenografts in nude mice. KM12C tumours treated with 5-FU showed less
      sensitivity to 5-FU with an inhibition rate (IR) of 7.9%, while non-treated
      tumours were highly sensitive to 5-FU with an IR of 81.8%. To clarify the
      mechanism of 5-FU-resistance, the activities of various enzymes and gene
      expressions involved in the metabolism of 5-FU in both parental and 5-FU-treated
      KM12C tumours were measured. A 2- to 3-fold increase in thymidylate synthase (TS)
      activity and 4- to 5-fold decrease in ribonucleotide reductase (RNR) activity
      were observed in 5-FU-resistant KM12C tumours, while the activities of orotate
      phosphoribosyltransferase (OPRT) thymidine and uridine phosphorylases (TP,UP) and
      thymidine kinase (TK) were not markedly changed as a consequence of repeated
      treatment of KM12C tumours with 5-FU. The expression of TS mRNA was also
      amplified in accordance with the increased TS activity in a 5-FU-treated tumour
      sub-line (KM12C/5-FU) compared with that in parental tumours, but changed
      expressions of both RNR-R1 and RNA-R2 mRNA could not be detected in the 5-FU
      resistant tumour sub-line compared with the parental tumours, suggesting possible
      post-transcriptional regulation of RNR. Moreover, RNR, in addition to TS and
      OPRT, seemed to be related to the inherent insensitivity to 5-FU in human cancer
      xenografts. From these results, it may be concluded that RNR activity is one of
      the acquired or inherent resistant factors, including TS, to 5-FU in human cancer
      xenografts in vivo.

PMID- 11527697
TI  - Ribozyme targeting of HER-2 inhibits pancreatic cancer cell growth in vivo.
AB  - We have analysed HER-2 expression and function in pancreatic cancer cells to
      determine whether HER-2 has a rate-limiting role for pancreatic cancer cell
      growth in vitro and in vivo. To specifically assess HER-2 function, we used HER-2
      targeted ribozymes expressed under the control of the tet-off promoter system.
      Six out of 11 human pancreatic cancer cell lines expressed all four epidermal
      growth factor (EGF)-receptor family members (HER-1 (EGF-R), HER-2, HER-3, and HER
      4), including Panc89 cells. Expression of the ribozymes quenched endogenous HER-2
      mRNA levels in Panc89 cells by approximately 40-60% which was reflected by a 40
      50% reduction of the HER-2 surface glycoprotein. HER-2 depletion inhibited the in
      vitro proliferation rate by approximately 40% and decreased in vivo tumour growth
      by approximately 60% (P<0.05). Our study demonstrates for the first time a rate
      limiting role for HER-2 in pancreatic cancer cell proliferation and suggests HER
      2 targeting as a potential approach in pancreatic cancer therapy.

PMID- 11527698
TI  - Decreased expression of Bid in human hepatocellular carcinoma is related to
      hepatitis B virus X protein.
AB  - As a mitochondrial membrane death ligand, Bid oligomerises Bak to release
      cytochrome C and its deficiency renders hepatocytes resistant to apoptosis
      induced by Fas. The Bid level in hepatocellular carcinoma (HCC) is unknown. In
      this report, we examined the expression of Bid protein and mRNA in HCC cancerous
      tissues and their corresponding non-cancerous ones. The effect of the hepatitis B
      x protein (HBx) on the expression of Bid was also evaluated by transfecting
      hepatoma cells with the HBx gene. The results showed that the expression of Bid
      was significantly lower in cancerous tissues than that in their corresponding non
      cancerous tissues. Immunohistochemical study revealed that Bid molecule was
      mainly localised in hepato-cytoplasm. Some nuclei were also positive for Bid
      antigen though to a lesser degree. In vitro experiments demonstrated that the
      expression of Bid in cells transfected with HBx was significantly lower than that
      in the cells without HBx transfection. This finding suggests that HBx may play a
      causative role in the reduction of Bid expression in HCC. This in vitro result
      is, to some degree, supported by clinical data that all the HCC examined are
      positive for hepatitis B virus (HBV). We conclude from this data that the
      expression of Bid in HCC is significantly decreased and the reduction of Bid may
      result from a mechanism associated with HBx, a major hepatocarcinogenic product
      from HBV. The imbalance of increased anti-apoptosis and decreased pro-apoptosis
      seen in HCC is a critical mechanism leading to the uncontrolled growth of tumour
      cells. Therefore, this study suggests that a deficiency in the expression of Bid
      may contribute to the development of such an imbalance in HCC.

PMID- 11527699
TI  - In vivo inhibition of tumour growth by dexamethasone in murine osteosarcomas.
AB  - This study was performed to determine whether glucocorticoid (GC) is an effective
      inhibitor of tumour growth in murine osteosarcoma (OS) in vivo. The effects of
      dexamethasone (DEX) on the growth of this tumour were studied in male C3H/He
      mice. The animals received a dose of 1.25 or 5 microg/g of DEX in 0.1 ml of
      steroid solution daily intraperitoneally (i.p.) for 14 days. In each DEX-treated
      group, significant inhibition of the tumour growth curve was seen in a dose-
      dependent manner compared with the control group (P<0.0001). The percentage of
      proliferative cell nuclear antigen (PCNA)-positive cells was 22.7% in the 5
      microg/g DEX treatment group compared with 67.6% in the control group (P=0.009).
      Furthermore, mifepristone, a GC receptor antagonist, blocked the inhibition of
      tumour growth induced by DEX. In the control group, tumour cells showed positive
      reactivity for nuclear glucocorticoid receptors (GR) by immunohistochemistry. The
      results of this study indicate that tumour growth inhibition by DEX in murine
      osteosarcoma may be via GR.

PMID- 11527700
TI  - T Lymphocytes infiltrating various tumour types express the MHC class II ligand
      lymphocyte activation gene-3 (LAG-3): role of LAG-3/MHC class II interactions in
      cell-cell contacts.
AB  - The product of the Lymphocyte Activation Gene-3 (LAG-3, CD223) is a high affinity
      MHC class II ligand expressed by activated CD4(+) and CD8(+) T cells, which can
      associate with the T cell receptor (TCR) and downregulate TCR signalling in
      vitro. We have also reported that a soluble mLAG-3Ig fusion protein works as a
      vaccine adjuvant in vivo in mice, enhancing Th1 and CD8 T cell responses. Here,
      we report that LAG-3 expression was found, using fluorescent activated cell
      sorting (FACS) analysis, on 11-48% of human tumour-infiltrating lymphocytes
      (TILs) isolated from eight freshly dissociated renal cell carcinomas (RCCs), and
      was restricted mostly to CD8(+) cells. Immunohistochemical analysis confirmed LAG
      3 expression by TILs in 9/11 RCCs, as well as in tumours of different origins,
      such as melanomas (3/5) and lymphomas (7/7). Since not only antigen presenting
      cells (APCs), but also TILs themselves strongly express major histocompatibility
      complex (MHC) class II, we firstly investigated whether LAG-3/MHC class II T-T
      cell contacts might influence tumour cell recognition. However, cytotoxicity
      inhibition was not observed in two RCC-specific CD8(+) T cell clones in the
      presence of the LAG-3-specific MAb, and there was also no observed difference in
      the recognition of LAG-3-transfected or wild-type RCC by these cytotoxic T
      lymphocytes (CTLs). In contrast, MHC class II engagement by LAG-3Ig was found to
      enhance the capacity of immature dendritic cells to stimulate naive T cell
      proliferation and IL-12-dependent IFN-gamma production by T cells in vitro. These
      results therefore provide support for a role for TIL-expressed LAG-3 in the
      engagement of class II molecules on APCs, thereby contributing to APC activation
      and Th1/Tc1 commitment, without downregulating cytotoxicity.

PMID- 11527701
TI  - An anti-apoptotic role for NGF receptors in human rhabdomyosarcoma.
AB  - The expression and biological function of Nerve Growth Factor (NGF) receptors was
      studied in a panel of rhabdomyosarcoma cell lines derived from embryonal and
      alveolar histotype. All the cell lines expressed both the high affinity receptor
      TrkA and the low affinity receptor p75(NTR). Treatment with exogenous NGF did not
      considerably alter rhabdomyosarcoma cell growth or differentiation, but
      significantly inhibited spontaneous apoptosis as well as apoptosis, and induced
      by serum starvation or apoptosis induced by treatment with cycloheximide (CHX).
      Rhabdomyosarcoma cell lines expressed NGF and other neurotrophins and trace
      amounts of NGF protein were found in the supernatants of rhabdomyosarcoma cell
      cultures. Blocking the putative autocrine loop with an anti-NGF antibody resulted
      in an increase in apoptosis compared with control cultures. These data suggest
      that the simultaneous presence of both high and low affinity NGF receptors
      engaged by endogenous or exogenous NGF might contribute to the escape from
      apoptosis exhibited by the rhabdomyosarcoma cells.

PMID- 11527703
TI  - Evolution of anti-HIV drug candidates. Part 1: From alpha-anilinophenylacetamide
      (alpha-APA) to imidoyl thiourea (ITU).
AB  - Stemming from work on a previous clinical candidate, loviride, and other alpha
      APA derivatives, a new series of potent non-nucleoside reverse transcriptase
      inhibitors (NNRTIs) has been synthesized. The ITU analogues, which contain a
      unique diarylated imidoyl thiourea, are very active in inhibiting both wild-type
      and clinically important mutant strains of HIV-1.

PMID- 11527704
TI  - Evolution of anti-HIV drug candidates. Part 2: Diaryltriazine (DATA) analogues.
AB  - A synthesis program directed toward improving the stability of imidoyl thiourea
      based non-nucleoside reverse transcriptase inhibitors (NNRTIs) led to the
      discovery of diaryltriazines (DATAs), a new class of potent NNRTIs. The synthesis
      and anti-HIV structure-activity relationship (SAR) studies of a series of DATA
      derivatives are described.

PMID- 11527705
TI  - Evolution of anti-HIV drug candidates. Part 3: Diarylpyrimidine (DAPY) analogues.
AB  - The synthesis and anti-HIV-1 activity of a series of diarylpyrimidines (DAPYs)
      are described. Several members of this novel class of non-nucleoside reverse
      transcriptase inhibitors (NNRTIs) are extremely potent against both wild-type and
      a panel of clinically significant single- and double-mutant strains of HIV-1.

PMID- 11527706
TI  - Inhibitors of bacterial enoyl acyl carrier protein reductase (FabI): 2,9
      disubstituted 1,2,3,4-tetrahydropyrido[3,4-b]indoles as potential antibacterial
      agents.
AB  - An SAR study of a screening lead has led to the identification of 2,9
      disubstituted 1,2,3,4-tetrahydropyrido[3,4-b]indoles as inhibitors of
      Staphylococcus aureus enoyl acyl carrier protein reductase (FabI).

PMID- 11527707
TI  - The mechanism of action of bacimethrin, a naturally occurring thiamin
      antimetabolite.
AB  - The mechanism of bacimethrin (2) toxicity has been determined. This compound is
      converted to 2'-methoxy-thiamin pyrophosphate (10) by the thiamin biosynthetic
      enzymes. Of the seven thiamin pyrophosphate utilizing enzymes in Escherichia
      coli, 2'-methoxy-thiamin pyrophosphate inhibits alpha-ketoglutarate
      dehydrogenase, transketolase, and deoxy-D-xylulose-5-phosphate synthase.
      Bacimethrin does not cause repression of the genes coding for the thiamin
      biosynthetic enzymes.

PMID- 11527708
TI  - Synthesis and microtubule binding of fluorescent paclitaxel derivatives.
AB  - The preparation of two new fluorescent derivatives of paclitaxel in which the
      fluorophore is bonded to paclitaxel at the C-10 position is reported. Both
      analogues, 10-deacetyl-10-(m-aminobenzoyl)paclitaxel (1, BTax) and 10-deacetyl-10
      [7-(diethylamino) coumarin-3-carbonyl]paclitaxel (2, CTax) retain good activity
      as promoters of in vitro tubulin assembly. Microtubule binding enhances the
      emission intensity of both probes.

PMID- 11527709
TI  - Optimization of a screening lead for factor VIIa/TF.
AB  - The structure-based design and progression of a screening lead to a 3nM factor
      VIIa/TF inhibitor with improved selectivity versus related enzymes is described.

PMID- 11527710
TI  - Synthesis of d-labeled N-alkylmaleimides and application to quantitative peptide
      analysis by isotope differential mass spectrometry.
AB  - d-Labeled N-alkylmaleimides have been prepared for specific modification of the
      terminal SH groups of cysteine residues in proteins or peptides. These reagents
      are useful tools for quantitative analysis of peptides by stable isotope
      differential mass spectrometry.

PMID- 11527711
TI  - Modulation of immunostimulatory activity of CpG oligonucleotides by site-specific
      deletion of nucleobases.
AB  - The effect of nucleobase deletion in the 3'- or the 5'-flanking sequence to a CpG
      motif on immunostimulatory activity of CpG-containing oligonucleotides was
      examined by cell proliferation, secretion of IL-12 and IL-6 in mouse spleen cell
      cultures, and by spleen enlargement in mice. Deletion of one or two nucleobases
      in the 3'-flanking sequence to a CpG-motif at certain positions did not affect
      immunostimulatory activity, while similar deletions in the 5'-flanking sequence
      increased immunostimulatory activity compared with the parent oligo.

PMID- 11527712
TI  - Antimalarial t-butylperoxyamines.
AB  - Twelve t-butylperoxyamines (6-17) were synthesized as targeted antimalarials and
      evaluated for antimalarial activity in vivo against Plasmodium berghei in mice
      and in vitro against both chloroquine sensitive and chloroquine resistant strains
      of Plasmodium falciparum. Compound 8 was found to have highest potency with
      activity at 80 and 160mg/kg dose in vivo and compound 11 exhibited highest
      efficacy in vitro.

PMID- 11527713
TI  - Conformational search of antisense nucleotides.
AB  - A preliminary MMFF implementation of selenium atom parameters necessary to model
      the nucleoside 1 is reported. X-ray structures of two compounds 1 and 2 have been
      used as references. Ab initio methods have been adopted for checking torsional
      energy profile and charge distribution. Monte Carlo calculations and energy
      minimization in solvation complete the conformational search.

PMID- 11527714
TI  - Design and synthesis of glycolic and mandelic acid derivatives as factor Xa
      inhibitors.
AB  - A series of glycolic and mandelic acid derivatives was synthesized and
      investigated for their factor Xa inhibitory activity. These analogues are highly
      potent and selective inhibitors against fXa. In a rabbit deep vein thrombosis
      model, compound 26 showed significant antithrombotic effects (81% inhibition of
      thrombus formation) at 1.1 microM plasma concentration following intravenous
      administration.

PMID- 11527715
TI  - Aminopyrazoles with high affinity for the human neuropeptide Y5 receptor.
AB  - 1,3-Disubstituted-5-aminopyrazoles were prepared based on a lead compound found
      through high-throughput screening of our corporate compound library in an assay
      measuring affinity for the human neuropeptide Y5 receptor. The target compounds
      were prepared by cyclization of alpha-cyanoketones with appropriate hydrazines,
      followed by reduction and coupling to various sulfonamido-carboxylic acids.
      Several of these arylpyrazoles (e.g., 19 and 45) displayed high affinity for the
      human NPY Y5 receptor (<20nM IC(50)s).

PMID- 11527716
TI  - Pyrazolecarboxamide human neuropeptide Y5 receptor ligands with in vivo
      antifeedant activity.
AB  - 1-Aryl-3-carboxamido-5-alkylpyrazoles were prepared based on a hit found in high
      throughput screening of our corporate compound library in an assay measuring
      affinity for the human neuropeptide Y5 receptor. 1-(3-Trifluoromethylphenyl)-3-[N
      (5-quinolinyl)carboxamido]-5-methylpyrazole (31) bound to the human neuropeptide
      Y5 receptor with a 80 nM IC(50 )and was shown to inhibit cumulative food
      consumption 43.2% 2-6 h after ip dosing in a fasting-induced feeding model in
      rats.

PMID- 11527717
TI  - Anti-AIDS agents. Part 47: Synthesis and anti-HIV activity of 3-substituted 3',4'
      Di-O-(S)-camphanoyl-(3'R,4'R)-(+)-cis-khellactone derivatives.
AB  - Six 3-substituted 3',4'-di-O-(S)-camphanoyl-(+)-cis-khellactone derivatives (3-8)
      were synthesized from 3-methyl DCK (2). 3-Hydroxymethyl DCK (6) exhibited potent
      anti-HIV activity in H9 lymphocytes with EC(50) and TI values of 1.87 x 10(-4)
      microM and 1.89 x 10(5), respectively. These values are similar to those of DCK
      and better than those of AZT in the same assay.

PMID- 11527719
TI  - Synthesis and biological evaluation of L- and D-configurations of 2',3'-dideoxy
      4'-C-methyl-3'-oxacytidine analogues.
AB  - Novel L- and D-configuration 2',3'-dideoxy-4'-C-methyl-3'-oxacytidine and their 5
      fluoro analogues have been synthesized from 1-benzyloxy-2-propanone and L
      ascorbic acid in eight steps and evaluated for biological activity.

PMID- 11527718
TI  - Synthesis and purine receptor affinity of 6-oxopurine nucleosides and nucleotides
      containing (N)-methanocarba-pseudoribose rings.
AB  - 6-Oxopurine derivatives containing a northern (N) methanocarba modification
      (i.e., fused cyclopropane and cyclopentane rings in place of the ribose) were
      synthesized and the adenosine receptor affinity measured. Guanine or hypoxanthine
      was coupled at the 7-position, or 1,3-dibutylxanthine was coupled at the 9
      position. The pseudoribose ring was also substituted at the 5'-position with an N
      methyluronamide or with phosphate groups.

PMID- 11527720
TI  - Imidazolopyrazinones as potential antioxidants.
AB  - A series of imidazolopyrazinones 3, substituted at C-2, and C-2/C-6, has been
      prepared. The compounds behaved as quenchers of superoxide anion. The more active
      compounds are structurally related to coelenterazine, a natural substrate of
      marine bioluminescence. Theoretical parameters based on Hartree-Fock
      instabilities have been examined.

PMID- 11527721
TI  - Metabolic stabilization of benzylidene ketal M(2) muscarinic receptor antagonists
      via halonaphthoic acid substitution.
AB  - The potential toxicological liabilities of the M(2) muscarinic antagonist 1 were
      addressed by replacing the methylenedioxyphenyl moiety with a p-methoxyphenyl
      group, resulting in M(2) selective compounds such as 3. Several halogenated
      naphthamide derivatives of 3 were studied in order to improve the pharmacokinetic
      profile via blockage of oxidative metabolism. Compound 4 demonstrated excellent
      M(2) affinity and selectivity, human microsomal stability, and oral
      bioavailability in rodents and primates.

PMID- 11527722
TI  - In vitro stability of alpha-helical peptide nucleic acids (alphaPNAs).
AB  - Alpha-helical peptide nucleic acids (alphaPNAs) are synthetic molecules that
      merge the alpha-helix secondary structure of peptides with the codified Watson
      Crick base pairing capability of nucleic acids. It is now demonstrated that
      alphaPNAs made up of either L- or D-amino acids are resistant to degradation by
      the proteases present in human serum. The increased stability of alphaPNAs
      towards proteases may be attributable to the presence of unnatural nucleoamino
      acid residues [-NHCH(CH(2)OCH(2)B)CO-, where B=thymine or cytosine] since the
      replacement of these amino acids by serine yields a control peptide that does
      break down in human serum. The stability of alphaPNAs towards proteases makes
      them attractive candidates for further development as antisense agents.

PMID- 11527723
TI  - A novel phosphotyrosine mimetic 4'-carboxymethyloxy-3'-phosphonophenylalanine
      (Cpp): exploitation in the design of nonpeptide inhibitors of pp60(Src) SH2
      domain.
AB  - The novel phosphotyrosine (pTyr) mimetic 4'-carboxymethyloxy-3'
      phosphonophenylalanine (Cpp) has been designed and incorporated into a series of
      nonpeptide inhibitors of the SH2 domain of pp60(c-Src) (Src) tyrosine kinase. A
      2.2 A X-ray crystal structure of 1a bound to a mutant form of Lck SH2 domain
      provides insight regarding the structure-activity relationships and supports the
      design concept of this new pTyr mimetic.

PMID- 11527724
TI  - Monocharged inhibitors of mast cell tryptase derived from potent and selective
      dibasic inhibitors.
AB  - Truncation of potent and selective dibasic inhibitors afforded monocharged
      inhibitors of human mast-cell tryptase. Using two classes of analogues as lead
      structures, several monocharged derivatives were identified with K(i) values
      ranging from 0.084 to 0.21 microM against the enzyme.

PMID- 11527725
TI  - Vinyl sulfonium as novel proteolytic enzyme inhibitor.
AB  - Vinyl sulfoniums were synthesized from vinyl sulfides by methylation, and
      inhibited the proteolytic enzyme papain. Inhibition studies suggest a mechanism
      by which the vinyl sulfonium inhibitor covalently and irreversibly modifies the
      enzyme.

PMID- 11527726
TI  - Rational design and synthesis of novel 2,5-disubstituted cis- and trans
      piperidine derivatives exhibiting differential activity for the dopamine
      transporter.
AB  - Herein, we report the rational design and synthesis of novel 2,5-disubstituted
      piperidine derivatives in the cis and trans isomeric forms. Out of these two
      isomers, the cis-isomer, 7a, was found to exhibit the most potent activity and
      selectivity for the dopamine transporter. These novel derivatives represent
      conformationally constrained version of piperidine analogue of GBR compounds.

PMID- 11527727
TI  - The synthesis and tubulin binding activity of thiophene-based analogues of
      combretastatin A-4.
AB  - A number of analogues of combretastatin A-4 (1), containing a thiophene ring
      interposed between the two phenyl groups, have been prepared. The synthesis of
      these compounds employed a combination of palladium-mediated coupling and
      iodocyclization techniques. The thiophene compounds 11, 14, 18, and 19 also
      represent non-benzofused analogues of some recently described tubulin binding
      benzo[b]thiophenes 3-5. The most active thiophene compounds identified in this
      study were 11, 14, and 18. Overall they are less active than 1 but exhibit
      comparable activity to the most active of the benzo[b]thiophenes 3-5. A structure
      activity relationship of these compounds is considered.

PMID- 11527728
TI  - New 1-aryl-4-(biarylmethylene)piperazines as potential atypical antipsychotics
      sharing dopamine D(2)-receptor and serotonin 5-HT(1A)-receptor affinities.
AB  - This paper describes the syntheses of several 1-aryl-4
      (biarylmethylene)piperazines and the results of the determination of their
      affinity for D(2) and 5-HT(1A) receptors. A selection of these compounds was
      evaluated in vivo, resulting in the identification of a drug candidate which is
      being clinically evaluated as a potential atypical antipsychotic with reduced
      extrapyrimidal side effects.

PMID- 11527729
TI  - Parallel solid-phase synthesis of zatebradine analogues as potential I(f) channel
      blockers.
AB  - The first solid-phase synthesis of zatebradine 1 and its analogues is reported.
      This has resulted in the preparation of compounds with increased ability to
      reduce the spontaneous beating of isolated guinea-pig atria in a concentration
      dependent manner. One example, 8g, showed a maximum reduction of beating of 80%
      at 3 microM compared to a reduction of 40% at 3 microM with zatebradine 1.

PMID- 11527730
TI  - Structure-activity relationship studies of a bisbenzimidazole-based, Zn(2+)
      dependent inhibitor of HCV NS3 serine protease.
AB  - A survey of isosteric replacements of the phosphonoalanine side chain coupled
      with a process of conformational constraint of a bisbenzimidazole-based, Zn(2+)
      dependent inhibitor of hepatitis C virus (HCV) NS3 serine protease resulted in
      the identification of novel series of active compounds with extended side chains.
      However, Zn(2+)-dependent HCV NS3 inhibition was relatively insensitive to the
      structural variations examined but dependent on the presence of negatively
      charged functionality. This result was interpreted in the context of an initial
      electrostatic interaction between protease and inhibitor that is subsequently
      consolidated by Zn(2+), with binding facilitated by the featureless active site
      and proximal regions of the HCV NS3 protein.

PMID- 11527731
TI  - A novel class of inhibitors for steroid 5alpha-reductase: synthesis and
      evaluation of umbelliferone derivatives.
AB  - A series of umbelliferone derivatives was prepared and their 5alpha-reductase
      type 1 inhibitory activities were evaluated in cell culture systems. Our studies
      have identified a new series of potent 5alpha-reductase type 1 inhibitors and
      provided the basis for further development for the treatment of human endocrine
      disorders associated with overproduction of DHT by 5alpha-reductase type 1. The
      preliminary structure-activity relationship was described to elucidate the
      essential structural requirements.

PMID- 11527732
TI  - Drug design, synthesis, and evaluation of a non-sugar-based selectin antagonist.
AB  - We have designed a series of simple rigid compounds (2) having a phenyl ring
      attached to three essential groups necessary for selectin binding, i.e., a fucose
      unit, a carboxylic acid, and the hydrophobic part. In this series of compound 2,
      2a exhibited strong inhibitory activity in in vitro P-selectin mediated cell
      adhesion assay. The novel type of compound 2a would be a potential lead compound
      for selectin antagonist.

PMID- 11527733
TI  - Synthesis and bioactivities of novel pyridazine derivatives: inhibitors of
      interleukin-1 beta (IL-1beta) production.
AB  - New pyridazine derivatives were prepared, and their abilities to inhibit IL-1beta
      production were evaluated. Some compounds showed potent inhibitory activity
      against IL-1beta production in HL-60 cells stimulated with lipopolysaccharide
      (LPS). The synthesis and structure-activity relationships of these compounds are
      described.

PMID- 11527734
TI  - Synthesis and bioactivities of novel 5,6-bis(4-methoxyphenyl)-2H-pyridazin-3-one
      derivatives: inhibitors of interleukin-1 beta (IL-1beta) production.
AB  - New 5,6-bis(4-methoxyphenyl)-2H-pyridazin-3-one derivatives were prepared, and
      their abilities to inhibit IL-1beta production were evaluated. Some compounds
      showed potent inhibitory activity against IL-1beta production in HL-60 cells
      stimulated with lipopolysaccharide (LPS). The synthesis and structure-activity
      relationships of these compounds are described.

PMID- 11527735
TI  - N-hydroxyl derivatives of guanidine based drugs as enzymatic NO donors.
AB  - Recent research suggests that NO may play a role in the physiological effects of
      some guanidine-containing drugs. In this report, three guanidine-containing drugs
      (guanadrel, guanoxan, and guanethidine) together with their N-hydroxyl
      derivatives were synthesized and their NO-releasing abilities catalyzed by nitric
      oxide synthases (NOSs) and horseradish peroxidase were evaluated. The guanidine
      containing compounds could not release NO in the presence of NOS or peroxidase.
      The corresponding N-hydroxyl compounds exhibited weak NO-releasing ability under
      the catalyzed of NOS and good NO-releasing ability under the oxidation by
      horseradish peroxidase in the presence of H(2)O(2). These compounds also
      displayed vasodilatory activity.

PMID- 11527736
TI  - 3'-Azidoabscisic acid as a photoaffinity reagent for abscisic acid binding
      proteins.
AB  - 3'-Azidoabscisic acid was synthesized as a potential photoaffinity reagent for
      abscisic acid binding proteins. This compound was stable in organic and aqueous
      solutions in the dark, but was decomposed by UV irradiation. Its biological
      activity was equivalent to that of abscisic acid, suggesting that it may be an
      effective photoaffinity reagent.

PMID- 11527737
TI  - Identification of a series of oxadiazole-substituted alpha-isopropoxy
      phenylpropanoic acids with activity on PPARalpha, PPARgamma, and PPARdelta.
AB  - A series of oxadiazole-substituted alpha-isopropoxy phenylpropanoic acids with
      dual agonist activity on PPARalpha and PPARgamma is described. Several of these
      compounds also showed partial agonist activity on PPARdelta. Resolution of one
      analogue showed that PPARalpha and PPARgamma activity resided in mainly one
      enantiomer, whereas PPARdelta activity was retained in both enantiomers.

PMID- 11527738
TI  - Utility of boron clusters for drug design. Hansch-fujita hydrophobic parameters
      pi of dicarba-closo-dodecaboranyl groups.
AB  - The spherical boron clusters, dicarba-closo-dodecaboranes (carboranes) are new
      hydrophobic pharmacophores, which interact hydrophobically with receptors. We
      have experimentally measured the partition coefficients log P for
      carboranylphenols employing an HPLC method, and determined the Hansch-Fujita
      hydrophobic parameters pi of various carboranyl groups. The values (pi=2.69-4.44)
      vary depending on the position of substitution on the carborane cage and the
      isomeric form (o-, m-, p-carboranes). These values lie within the range of those
      of hydrocarbons.

PMID- 11527739
TI  - An approach to the identification of potent inhibitors of influenza virus fusion
      using parallel synthesis methodology.
AB  - Structure-activity studies associated with the salicylic acid-derived inhibitor
      of influenza fusion, BMY-27709, were examined using a parallel synthesis
      approach. This SAR survey led to the discovery of potent influenza inhibitory
      activity in a series of aromatic amides and thioamides derived from 1,3,3
      trimethyl-5-hydroxycyclohexylmethylamine. Select compounds were characterized as
      inhibitors of the H1 subtype of influenza A viruses that act by preventing the pH
      induced fusion process, thereby blocking viral entry into host cells. In a plaque
      reduction assay, the most potent inhibitors displayed EC(50) values of 0.02-0.14
      microg/mL.

PMID- 11527740
TI  - Synthesis and biological properties of new 1beta-methylcarbapenems containing
      heteroaromatic thioether moiety.
AB  - The synthesis and biological activities of a series of new 1beta
      methylcarbapenems 1a-h having heteroaromatic thioether moiety at C-5 position of
      pyrrolidine were described. Among these compounds, 1,2,3-thiadiazole derivative
      1h showed the most potent antibacterial activity and advanced pharmacokinetics in
      comparison with meropenem.

PMID- 11527741
TI  - Hydrolysis of plasmid DNA catalyzed by Co(III) complex of cyclen attached to
      polystyrene.
AB  - Reactivity of the Co(III) complex of cyclen (CoCyc) in the hydrolytic cleavage of
      supercoiled pUC18 DNA leading to the formation of the corresponding open circular
      form was enhanced by >200 times upon attachment of CoCyc to cross-linked
      polystyrenes. Thus, half-lives as short as 40 min were achieved by the resin
      based CoCyc in cleavage of the supercoiled DNA at 4 degrees C.

PMID- 11527742
TI  - Development of C-20 modified betulinic acid derivatives as antitumor agents.
AB  - Chemical modifications were performed on C-20 position of betulinic acid for a
      structure-activity relationship study. The evaluation of the compounds using
      human colon carcinoma HCT-116, human prostate adenocarcinoma PC3, and human
      melanoma cell lines M14-MEL, SK-MEL-2, and UACC-257 did not show any selective
      cytotoxicity towards melanoma cells. The results from both MTT reduction assay
      and SRB staining assay were comparable that no remarkable differences in
      cytotoxicity profile of the compounds were noticed. The C-20 position was found
      to be sensitive to the size and the electron density of the substituents in
      retaining the cytotoxicity of betulinic acid and was found to be undesirable
      position to derivatize.

PMID- 11527745
TI  - PARASCANDOLA RESPONDS.

PMID- 11527746
TI  - Air pollution, weather stress, and blood pressure.

PMID- 11527748
TI  - ERRATUM.

PMID- 11527747
TI  - Cigarettes and the Surgeon General's report.

PMID- 11527749
TI  - IBALD-MULLI AND PETERS RESPOND.

PMID- 11527751
TI  - Confronting global AIDS: prevention and treatment.

PMID- 11527752
TI  - Public health and changes in illicit drug prices.

PMID- 11527753
TI  - Reenergizing public health through precaution.
AB  - The precautionary principle has provoked a spirited debate among
      environmentalists worldwide, but it is equally relevant to public health and
      shares much with primary prevention. Its central components are (1) taking
      preventive action in the face of uncertainty; (2) shifting the burden of proof to
      the proponents of an activity; (3) exploring a wide range of alternatives to
      possibly harmful actions; and (4) increasing public participation in decision
      making. Precaution is relevant to public health, because it can help to prevent
      unintended consequences of well-intentioned public health interventions by
      ensuring a more thorough assessment of the problems and proposed solutions. It
      can also be a positive force for change. Three aspects are stressed: promoting
      the search for safer technologies, encouraging greater democracy and openness in
      public health policy, and stimulating reevaluation of the methods of public
      health science.

PMID- 11527754
TI  - The precautionary principle and electric and magnetic fields.
AB  - Current environmental regulation represents a paternalistic policy, more
      concerned to avoid false postives than false negatives, limiting opportunities
      for individuals to make choices between risk-avoidance and risk-taking
      alternatives. For example, many exposures to magnetic fields could be reduced at
      little or no cost but are not considered seriously, owing to the uncertainty of
      risk and the concern to avoid false positives. Even though precautionary ap
      proaches that focus on avoiding false negatives often do not lead to adverse
      economic consequences or irrational choices, such approaches usually are not
      taken. The value of autonomy and the proper role of governmental paternalism with
      respect to environmental policy need to be considered more carefully in
      environmental decision making.

PMID- 11527756
TI  - The professions of public health.
AB  - Law has been an essential tool of public health practice for centuries. From the
      19th century until recent decades, however, most histories of public health
      described, approvingly, the progression of the field from marginally useful
      policy, made by persons learned in law, to effective policy, made by persons
      employing the methods of biomedical and behavioral science. Historians have
      recently begun to change this standard account by documenting the centrality of
      law in the development of public health practice. The revised history of public
      health offers additional justification for the program of public health law
      reform proposed in this issue of the Journal by Gostin and by Moulton and
      Matthews, who describe the new program in public health law of the Centers for
      Disease Control and Prevention.

PMID- 11527755
TI  - The precautionary principle also applies to public health actions.
AB  - The precautionary principle asserts that the burden of proof for potentially
      harmful actions by industry or government rests on the assurance of safety and
      that when there are threats of serious damage, scientific uncertainty must be
      resolved in favor of prevention. Yet we in public health are sometimes guilty of
      not adhering to this principle. Examples of actions with unintended negative
      consequences include the addition of methyl tert-butyl ether to gasoline in the
      United States to decrease air pollution, the drilling of tube wells in Bangladesh
      to avoid surface water microbial contamination, and villagewide parenteral
      antischistosomiasis therapy in Egypt. Each of these actions had unintended
      negative consequences. Lessons include the importance of multidisciplinary
      approaches to public health and the value of risk-benefit analysis, of public
      health surveillance, and of a functioning tort system-all of which contribute to
      effective precautionary approaches.

PMID- 11527757
TI  - Public health law reform.
AB  - Public health law reform is necessary because existing statutes are outdated,
      contain multiple layers of regulation, and are inconsistent. A model law would
      define the mission and functions of public health agen cies, provide a full range
      of flexible powers, specify clear criteria and procedures for activities, and
      provide protections for privacy and against discrimination. The law reform
      process provides an opportunity for public health agencies to draw attention to
      their resource needs and achievements and to form ties with constituency groups
      and enduring relations with the legislative branch of government. Ultimately, the
      law should become a catalyst, rather than an impediment, to reinvigorating the
      public health system.

PMID- 11527758
TI  - Strengthening the legal foundation for public health practice: a framework for
      action.
AB  - Growing concern that public health laws may be inadequate to the challenges that
      confront public health practitioners has led to adoption of a Healthy People 2010
      objective for improved laws and policies. It has also led to concerted efforts to
      strengthen the legal foundation for public health practice. In this editorial,
      the authors present a framework for collaborative research, analysis, and
      development to strengthen public health laws, skill in applying laws, and law
      related information resources.

PMID- 11527759
TI  - Night shift in a glass factory.

PMID- 11527760
TI  - Radioactivity and rights: clashes at Bikini Atoll.
AB  - Cash can never compensate people for a half century of exile and the destruction
      of a lifestyle and culture.

PMID- 11527761
TI  - Retaining hard-to-reach women in HIV prevention and vaccine trials: Project
      ACHIEVE.
AB  - Project ACHIEVE, which conducts HIV prevention research studies, maintains a
      women's site in the South Bronx in NewYork City. Owing to a focused retention
      effort at the South Bronx site, high retention rates were achieved in a vaccine
      preparedness study for women at high risk of HIV infection. Comparable retention
      rates have been achieved in HIV vaccine trials with similar cohorts of women at
      this site. These results suggest that concerns about retaining hard-to-reach
      populations should not cause these populations to be excluded from HIV vaccine
      and prevention trials.

PMID- 11527762
TI  - De morbis artificum diatriba [diseases of workers]. 1713.

PMID- 11527763
TI  - Bernardino Ramazzini: The Father of Occupational Medicine.

PMID- 11527764
TI  - Minority women and advocacy for women's health.
AB  - US minority health issues involve racial/ethnic disparities that affect both
      women and men. However, women's health advocacy in the United States does not
      consistently address problems specific to minority women. The underlying
      evolution and political strength of the women's health and minority health
      movements differ profoundly. Women of color comprise only one quarter of women's
      health movement constituents and are, on average, socioeconomically
      disadvantaged. Potential alliances may be inhibited by vestiges of historical
      racial and social divisions that detract from feelings of commonality and mutual
      support. Nevertheless, insufficient attention to minority women's issues
      undermines the legitimacy of the women's health movement and may prevent
      important advances that can be achieved only when diversity is fully considered.

PMID- 11527765
TI  - Informational privacy and the public's health: the Model State Public Health
      Privacy Act.
AB  - Protecting public health requires the acquisition, use, and storage of extensive
      health-related information about individuals. The electronic accumulation and
      exchange of personal data promises significant public health benefits but also
      threatens individual privacy; breaches of privacy can lead to individual
      discrimination in employment, insurance, and government programs. Individuals
      concerned about privacy invasions may avoid clinical or public health tests,
      treatments, or research. Although individual privacy protections are critical,
      comprehensive federal privacy protections do not adequately protect public health
      data, and existing state privacy laws are inconsistent and fragmented. The Model
      State Public Health Privacy Act provides strong privacy safeguards for public
      health data while preserving the ability of state and local public health
      departments to act for the common good.

PMID- 11527766
TI  - Coverage of tobacco dependence treatments for pregnant smokers in health
      maintenance organizations.

PMID- 11527767
TI  - Geographic variations in asthma mortality in Erie and Niagara counties, western
      New York, 1991-1996.

PMID- 11527768
TI  - Seat belt use in top-grossing movies vs actual US rates, 1978-1998.

PMID- 11527769
TI  - Local lead data are needed for local decision making.

PMID- 11527770
TI  - Estimation of health benefits from a local living wage ordinance.
AB  - OBJECTIVES: This study estimated the magnitude of health improvements resulting
      from a proposed living wage ordinance in San Francisco. METHODS: Published
      observational models of the relationship of income to health were applied to
      predict improvements in health outcomes associated with proposed wage increases
      in San Francisco. RESULTS: With adoption of a living wage of $11.00 per hour, we
      predict decreases in premature death from all causes for adults aged 24 to 44
      years working full-time in families whose current annual income is $20,000 (for
      men, relative hazard [RH] = 0.94, 95% confidence interval [CI] = 0.92, 0.97; for
      women, RH = 0.96, 95% CI = 0.95, 0.98). Improvements in subjectively rated health
      and reductions in the number of days sick in bed, in limitations of work and
      activities of daily living, and in depressive symptoms were also predicted, as
      were increases in daily alcohol consumption. For the offspring of full-time
      workers currently earning $20,000, a living wage predicts an increase of 0.25
      years (95% CI = 0.20, 0.30) of completed education, increased odds of completing
      high school (odds ratio = 1.34, 95% CI = 1.20, 1.49), and a reduced risk of early
      childbirth (RH = 0.78, 95% CI = 0.69, 0.86). CONCLUSIONS: A living wage in San
      Francisco is associated with substantial health improvement.

PMID- 11527771
TI  - Keeping the unemployed healthy: the effect of means-tested and entitlement
      benefits in Britain, Germany, and the United States.
AB  - OBJECTIVES: Although considerable evidence about the health effects of
      unemployment exists, little is known about the possible protective effects of
      various social interventions. This study examined the role that means-tested and
      entitlement programs could have in ameliorating the health impact of unemployment
      in Britain, Germany, and the United States. METHODS: Logistic regression models
      were used to analyze panel data from Britain (1991-1993), Germany (1991-1993),
      and the United States (1985-1987) available in the Household Panel Comparability
      Project database. The analysis included 8,726 respondents from Britain, 11,086
      from Germany, and 11,668 from the United States. The health-dependent variable
      used was a single measure of perceived health status. RESULTS: Evidence was found
      of differences in perceived health status between groups of unemployed people
      characterized by the types of benefits they receive. When socioeconomic
      characteristics and previous health and employment status are controlled for,
      means-tested benefits do not seem sufficient to reduce the impact of unemployment
      on health. CONCLUSIONS: Monitoring the possible health effects of changes in
      public assistance benefits should be given priority in the research and political
      agenda.

PMID- 11527772
TI  - Coverage of smoking cessation treatment by union health and welfare funds.
AB  - OBJECTIVES: This study determined the level of insurance coverage for smoking
      cessation treatment and factors associated with coverage among health and welfare
      funds affiliated with a large labor union. METHODS: A self-administered written
      survey was mailed to fund and union officials. Analyses were conducted by chi2
      tests. RESULTS: Twenty-nine percent of funds provided coverage for some type of
      smoking cessation treatment, with the odds of coverage significantly increased
      among funds whose administrators reported having received members' requests for
      smoking cessation treatment in the past year (odds ratio = 4.9, P = .05).
      CONCLUSIONS: Coverage for smoking cessation services is low, comparable to
      coverage offered by other health insurers. Interventions with union members and
      fund officials are needed to provide union members with access to affordable and
      effective smoking cessation treatments.

PMID- 11527773
TI  - The short-term impact of national smoke-free workplace legislation on passive
      smoking and tobacco use.
AB  - OBJECTIVES: This study sought to evaluate the short-term impact of national smoke
      free workplace legislation on employee exposure to environmental tobacco smoke at
      work and on employee smoking habits. METHODS: We performed 2 cross-sectional
      studies in 9 medium-sized and large Finnish workplaces, before and after
      implementation of national smoke-free workplace legislation. We assessed tobacco
      smoke exposure via questionnaire and indoor air nicotine measurements. RESULTS:
      Exposure to environmental tobacco smoke declined considerably after the
      legislation was implemented. Tobacco consumption among smokers diminished.
      Nicotine concentrations fell significantly. CONCLUSIONS: Legislation was more
      efficient than voluntary workplace-specific smoking restrictions in reducing
      passive smoking and cigarette consumption.

PMID- 11527774
TI  - The smoke you don't see: uncovering tobacco industry scientific strategies aimed
      against environmental tobacco smoke policies.
AB  - OBJECTIVES: This review details the tobacco industry's scientific campaign aimed
      against policies addressing environmental tobacco smoke (ETS) and efforts to
      undermine US regulatory agencies from approximately 1988 to 1993. METHODS: The
      public availability of more than 40 million internal, once-secret tobacco company
      documents allowed an unedited and historical look at tobacco industry strategies.
      RESULTS: The analysis showed that the tobacco industry went to great lengths to
      battle the ETS issue worldwide by camouflaging its involvement and creating an
      impression of legitimate, unbiased scientific research. CONCLUSIONS: There is a
      need for further international monitoring of industry-produced science and for
      significant improvements in tobacco document accessibility.

PMID- 11527775
TI  - Cigarette smoking behavior among US Latino men and women from different countries
      of origin.
AB  - OBJECTIVES: This study sought to compare smoking behavior among Latino men and
      women from different countries of origin. METHODS: A telephone-administered
      survey was conducted in 8 cities with Latino men and women of different national
      origin living in census tracts with at least 70% Latino individuals. RESULTS: A
      total of 8882 participants completed the survey; 53% were women. The average age
      of respondents was 44 years; 63% were foreign-born, and 59% preferred Spanish for
      the interview. Current smoking was more prevalent among men (25.0%, 95%
      confidence interval [CI] = 23.7, 26.3) than among women (12.1%, 95% CI = 11.1,
      13.0). Smoking rates were not significantly different by national origin among
      men, but Puerto Rican women had higher rates of smoking than other women. Central
      American men and women had the lowest smoking rates. Foreign-born respondents
      were less likely to be smokers (odds ratio [OR] = 0.77, 95% CI = 0.66, 0.90) than
      US-born respondents, and respondents with 12 years or less of education had an
      increased odds of smoking (OR = 1.17, 95% CI = 1.01, 1.35). High ac culturation
      was associated with more smoking in women (OR = 1.12, 95% CI = 1.00-1.25) and
      less smoking in men (OR = 0.86, 95% CI = 0.78-0.95). Puerto Rican and Cuban
      respondents were more likely to be current smokers and to smoke more than 20
      cigarettes per day. CONCLUSIONS: Older, US-born, and more-educated respondents
      were less likely to be current smokers. Respondents of Puerto Rican and Cuban
      origin were more likely to smoke. Acculturation has divergent effects on smoking
      behavior by sex.

PMID- 11527776
TI  - Changes in access to mental health care among the poor and nonpoor: results from
      the health care reform in Puerto Rico.
AB  - OBJECTIVES: Health care reforms associated with managed care may adversely affect
      the health care safety net for disadvantaged populations. This study compared
      changes in health care use among poor and nonpoor individuals enrolled in managed
      care. METHODS: Data from 3 waves of a random community sample were collected on
      approximately 3,000 adults. Changes in use of mental health services were
      assessed in a pretest-posttest, quasi-experimental design. RESULTS: Managed care
      increased use of specialty services among the nonpoor while maintaining the same
      level of use for the poor in the public sector. CONCLUSIONS: Reallocation of
      mental health services may be a result of expanding Medicaid eligibility.

PMID- 11527778
TI  - Modeling the cost and outcomes of pharmacist-prescribed emergency contraception.
AB  - OBJECTIVES: This study investigated the effect on the risk and cost of unintended
      pregnancies of emergency contraceptive pills obtained directly from a pharmacist.
      METHODS: We used a decision model to compare outcomes for private and public
      payers following unprotected intercourse from. RESULTS: Obtaining emergency
      contraceptive pills from a pharmacy, compared with obtaining them from a
      physician or clinic, resulted in a $158 (95% confidence interval (CI) =$76, $269)
      reduction in costs for private payers and a $48 (95% CI = $16, $93) reduction for
      public payers. CONCLUSIONS: Our findings suggest that under varied assumptions,
      obtaining emergency contraceptive pills directly from a pharmacist reduces the
      number of unintended pregnancies and is cost saving.

PMID- 11527777
TI  - Psychologic distress and natural menopause: a multiethnic community study.
AB  - OBJECTIVES: This study examined the association between psychologic distress and
      natural menopause in a community sample of African American, White, Chinese,
      Hispanic, and Japanese women participating in a national women's health study.
      METHODS: A cohort of 16,065 women aged 40 to 55 years provided information on
      menstrual regularity in the previous year, psychosocial factors, health, and
      somatic-psychologic symptoms. Psychologic distress was defined as feeling tense,
      depressed, and irritable in the previous 2 weeks. RESULTS: Rates of psychologic
      distress were highest in early perimenopause (28.9%) and lowest in premenopause
      (20.9%) and postmenopause (22%). In comparison with premenopausal women, early
      perimenopausal women were at a greater risk of distress, with and without
      adjustment for vasomotor and sleep symptoms and covariates. Odds of distress were
      significantly higher for Whites than for the other racial/ethnic groups.
      CONCLUSIONS: Psychologic distress is associated with irregular menses in midlife.
      It is important to determine whether distress is linked to alterations in hormone
      levels and to what extent a mood-hormone relationship may be influenced by
      socioeconomic and cultural factors.

PMID- 11527779
TI  - Drug prices and emergency department mentions for cocaine and heroin.
AB  - OBJECTIVES: In this report, the author illustrates the historic relation between
      retail drug prices and emergency department mentions for cocaine and heroin.
      METHODS: Price series based on the Drug Enforcement Administration's System to
      Retrieve Information From Drug Evidence database were correlated with data on
      emergency department mentions from the DrugAbuse Warning Network for cocaine
      (1978-1996) and heroin (1981-1996). RESULTS: A simple model in which emergency
      department mentions are driven by only prices explains more than 95% of the
      variation in emergency department mentions. CONCLUSIONS: Fluctuations in prices
      are an important determinant of adverse health outcomes associated with drugs.

PMID- 11527780
TI  - Eligibility under State Children's Health Insurance Programs.
AB  - OBJECTIVES: This study analyzed associations between income eligibility criteria
      under the State Children's Health Insurance Program (SCHIP) and state
      characteristics. METHODS: We used multivariate methods to explore relations
      between eligibility expansions under SCHIP and percentages of uninsured children
      from low-income families, per capita income, and political characteristics.
      RESULTS: Proportions of uninsured children, per capita income, and states'
      preexisting eligibility thresholds were statistically associated with changes in
      eligibility thresholds, whereas only per capita income was associated with
      overall SCHIP eligibility thresholds. Political dynamics were not statistically
      related to SCHIP expansions. CONCLUSIONS: State demographic characteristics were
      associated with changes in eligibility from preexisting levels but rarely were
      associated with SCHIP eligibility thresholds.

PMID- 11527781
TI  - Does investor ownership of nursing homes compromise the quality of care?
AB  - OBJECTIVES: Two thirds of nursing homes are investor owned. This study examined
      whether investor ownership affects quality. METHODS: We analyzed 1998 data from
      state inspections of 13,693 nursing facilities. We used a multivariate model and
      controlled for case mix, facility characteristics, and location. RESULTS:
      Investor-owned facilities averaged 5.89 deficiencies per home, 46.5% higher than
      nonprofit facilities and 43.0% higher than public facilities. In multivariate
      analysis, investor ownership predicted 0.679 additional deficiencies per home;
      chain ownership predicted an additional 0.633 deficiencies. Nurse staffing was
      lower at investor-owned nursing homes. CONCLUSIONS: Investor-owned nursing homes
      provide worse care and less nursing care than do not-for-profit or public homes.

PMID- 11527782
TI  - Cost-effectiveness of earlier initiation of antiretroviral therapy for uninsured
      HIV-infected adults.
AB  - OBJECTIVES: This study was designed to examine the societal cost-effectiveness
      and the impact on government payers of earlier initiation of antiretroviral
      therapy for uninsured HIV-infected adults. METHODS: A state-transition simulation
      model of HIV disease was used. Data were derived from the Multicenter AIDS Cohort
      Study, published randomized trials, and medical care cost estimates for all
      government payers and for Massachusetts, NewYork, and Florida. RESULTS: Quality
      adjusted life expectancy increased from 7.64 years with therapy initiated at 200
      CD4 cells/microL to 8.21 years with therapy initiated at 500 CD4 cells/microL.
      Initiating therapy at 500 CD4/microL was a more efficient use of resources than
      initiating therapy at 200 CD4/microL and had an incremental cost-effectiveness
      ratio of $17,300 per quality-adjusted life-year gained, compared with no therapy.
      Costs to state payers in the first 5 years ranged from $5,500 to $24,900 because
      of differences among the states in the availability of federal funds forAIDS drug
      assistance programs. CONCLUSIONS: Antiretroviral therapy initiated at 500 CD4
      cells/microL is cost-effective from a societal: perspective compared with therapy
      initiated later. States should consider Medicaid waivers to expand access to
      early therapy.

PMID- 11527783
TI  - Health and federal budgetary effects of increasing access to antiretroviral
      medications for HIV by expanding Medicaid.
AB  - OBJECTIVES. This study modeled the health and federal fiscal effects of expanding
      Medicaid for HIV-infected people to improve access to highly active
      antiretroviral therapy. METHODS: A disease state model of the US HIV epidemic,
      with and without Medicaid expansion, was used. Eligibility required a CD4 cell
      count less than 500/mm3 or viral load greater than 10,000, absent or inadequate
      medication insurance, and annual income less than $10,000. Two benefits were
      modeled, "full" and "limited" (medications, outpatient care). Federal spending
      for Medicaid, Medicare, AIDS Drug Assistance Program, Supplemental Security
      Income, and Social Security Disability Insurance were assessed. RESULTS: An
      estimated 38,000 individuals would enroll in a Medicaid HIV expansion. Over 5
      years, expansion would prevent an estimated 13,000 AIDS diagnoses and 2600 deaths
      and add 5,816 years of life. Net federal costs for all programs are $739 million
      (full benefits) and $480 million (limited benefits); for Medicaid alone, the
      costs are $1.43 and $1.17 billion, respectively. Results were sensitive to
      awareness of serostatus, highly active antiretroviral therapy cost, and
      participation rate. Strategies for federal cost neutrality include Medicaid HIV
      drug price reductions as low as 9% and private insurance buy-ins. CONCLUSIONS:
      Expansion of the Medicaid eligibility to increase access to antiretroviral
      therapy would have substantial health benefits at affordable costs.

PMID- 11527784
TI  - Use of protease inhibitors and non-nucleoside reverse transcriptase inhibitors
      among Medicaid beneficiaries with AIDS.
AB  - OBJECTIVES: This study compared the use of new antiretroviral treatments across
      sociodemographic subgroups during the 3 years after the introduction of these
      treatments and examined diffusion of the therapies over time. METHODS: Merged
      surveillance and claims data were used to examine use of protease inhibitors and
      non-nucleoside reverse transcriptase inhibitors (PI/NNRTIs) among New Jersey
      Medicaid beneficiaries with AIDS. RESULTS: In 1996, there were sharp disparities
      in use of PI/NNRTI therapy among racial minorities and injection drug users, even
      after control for other patient characteristics. These gaps had decreased by
      1998. Higher PI/NNRTI treatment rates were also observed among beneficiaries
      enrolled in a statewide HIV/AIDS-specific home- and community-based Medicaid
      waiver program. CONCLUSIONS: Even within a population of individuals similar in
      regard to health coverage, there were substantial sociodemographic differences in
      use of PI/NNRTIs during the early years after their introduction. These
      differences narrowed as new treatments became standard. Participation in a case
      managed Medicaid waiver program seems to be associated with a more appropriate
      pattern of use. These results suggest a need to address nonfinancial barriers to
      care.

PMID- 11527785
TI  - Differential HIV risk in bathhouses and public cruising areas.
AB  - OBJECTIVES: This report investigates differences in risk behaviors among men who
      have sex with men (MSM) who went to gay bathhouses, public cruising areas, or
      both. METHODS: We used a probability sample of MSM residing in 4 US cities (n =
      2,881). RESULTS: Men who used party drugs and had unprotected anal intercourse
      with nonprimary partners were more likely to go to sex venues than men who did
      not. Among attendees, MSM who went to public cruising areas only were least
      likely, and those who went to both public cruising areas and bathhouses were most
      likely to report risky sex in public settings. CONCLUSIONS: Distinguishing
      between sex venues previously treated as a single construct revealed a
      significant association between pattern of venue use and sexual risk. Targeting
      HIV prevention in the bathhouses would reach the segment of men at greatest risk
      for HIV transmission.

PMID- 11527786
TI  - Neighborhood poverty and the resurgence of tuberculosis in New York City, 1984
      1992.
AB  - OBJECTIVES: The resurgence of tuberculosis (TB) in NewYork City has been
      attributed to AIDS and immigration; however, the role of poverty in the epidemic
      is unclear. We assessed the relation between neighborhood poverty and TB at the
      height of the epidemic and longitudinally from 1984 through 1992. METHODS: Census
      block groups were used as proxies for neighborhoods. For each neighborhood, we
      calculated TB and AIDS incidence in 1984 and 1992 with data from the Bureaus of
      Tuberculosis Control and AIDS Surveillance and obtained poverty rates from the
      census. RESULTS: For 1992, 3,343 TB cases were mapped to 5,482 neighborhoods,
      yielding a mean incidence of 46.5 per 100,000. Neighborhood poverty was
      associated with TB (relative risk = 1.33; 95% confidence interval = 1.30, 1.36
      per 10% increase in poverty). This association persisted after adjustment for
      AIDS, proportion foreign born, and race/ethnicity. Neighborhoods with declining
      income from 1980 to 1990 had larger increases in TB incidence than did
      neighborhoods with increasing income. CONCLUSIONS: Leading up to and at the
      height of the TB epidemic in New York City, neighborhood poverty was strongly
      associated with TB incidence. Public health interventions should target
      impoverished areas.

PMID- 11527787
TI  - Poverty, race/ethnicity, and psychiatric disorder: a study of rural children.
AB  - OBJECTIVES: This study examined the effect of poverty on the prevalence of
      psychiatric disorder in rural Black and White children. METHODS: A representative
      sample of 541 Black children and 379 White children aged 9 to 17 was drawn from 4
      predominantly rural counties. Structured interviews with parents and children
      collected information on psychiatric disorders, absolute and relative poverty,
      and risk factors for psychiatric disorder. RESULTS: Three-month prevalence of
      psychiatric disorder was similar to that found in other community samples (20%).
      Federal criteria for poverty were met by 18% of the White and 52% of the Black
      families. Black and White children were exposed to equal numbers of risk factors
      overall, but the association between poverty and psychopathology was stronger for
      White children (odds ratio [OR] = 2.1; 95% confidence interval [CI] = 1.1, 4.2)
      than for Black children (OR = 1.5; 95% CI = 0.9, 2.6). Family history of mental
      illness, poor parenting, and residential instability mediated this association in
      both groups. CONCLUSIONS: In this rural sample, poverty was only weakly
      associated with child psychiatric disorders. Risk factors for both racial/ethnic
      groups were family mental illness, multiple moves, lack of parental warmth, lax
      supervision, and harsh punishment.

PMID- 11527788
TI  - Local increases in coronary heart disease mortality among blacks and whites in
      the United States, 1985-1995.
AB  - OBJECTIVES: This study analyzed coronary heart disease (CHD) mortality trends
      from 1985 to 1995, by race and sex, among Black and White adults 35 years and
      older to determine whether adverse trends were evident in any US localities.
      METHODS: Log-linear regression models of annual age-adjusted death rates provided
      a quantitative measure of local mortality trends. RESULTS: Increasing trends in
      CHD mortality were observed in 11 of 174 labor market areas for Black women, 23
      of 175 areas for Black men, 10 of 394 areas for White women, and 4 of 394 areas
      for White men. Nationwide, adverse trends affected 1.7% of Black women, 8.0% of
      Black men, 1.1% of White women, and 0.3% of White men. CONCLUSIONS: From 1985 to
      1995, moderate to strong local increases in CHD mortality were observed,
      predominantly in the southern United States. Black men evidenced the most
      unfavorable trends and were 25 times as likely as White men to be part of a local
      population experiencing increases in coronary heart disease mortality.

PMID- 11527789
TI  - Registry-driven, community-based immunization outreach: a randomized controlled
      trial.
AB  - OBJECTIVES: This study evaluated the effectiveness of registry-driven, community
      based outreach directed toward children with immunization delays. METHODS: A
      sample of 1,856 children aged 6 to 10 months was randomly assigned to receive
      either outreach or no intervention. RESULTS: Children in the outreach group were
      more likely to receive an immunization during the observation period than
      children in the control group (61% vs 43%). Outreach was most effective for
      children with multiple risks, as measured by their immunization record; it was
      not effective for children whose mothers had received inadequate prenatal care.
      CONCLUSIONS: Registry-driven outreach can effectively identify high-risk children
      and bring them to care.

PMID- 11527790
TI  - The quality improvement-research divide and the need for external oversight.
AB  - Historically, quality assurance studies have received scant ethical attention.
      The advent of information systems capable of supporting research-grade continuous
      quality improvement projects demands that we clearly define how these projects
      differ from research and when they require external review. The ethical
      obligation for the performance of quality assurance projects, with its emphasis
      on identifiable immediate action for a served population, is a critical
      distinction. The obligation to perform continuous quality improvement is a
      deliverable of the social contract entered into implicitly by patients and health
      care providers and systems. In this article, the authors review the ethical
      framework that requires these studies, evaluate the differences between quality
      assurance studies and classic research, and propose criteria for requiring
      external review.

PMID- 11527791
TI  - Retinopathies associated with antiretinal antibodies.

PMID- 11527792
TI  - Use of intravenous immunoglobulins for prophylaxis or treatment of infectious
      diseases.

PMID- 11527793
TI  - African enigma: key player in human immunodeficiency virus pathogenesis in
      developing countries?

PMID- 11527794
TI  - Reciprocal interaction of human immunodeficiency virus and hepatitis C virus
      infections.

PMID- 11527795
TI  - Development and validation of a gamma interferon ELISPOT assay for quantitation
      of cellular immune responses to varicella-zoster virus.
AB  - Cell-mediated immunity appears to be critical for the prevention and control of
      varicella-zoster virus (VZV) infection and complications arising from zoster.
      Current assays of VZV-specific cell-mediated immunity are cumbersome or lack
      sensitivity. We have developed a gamma interferon ELISPOT assay that provides a
      direct measure of the number of T cells secreting a cytokine following
      stimulation with antigen. This assay is extremely sensitive and specific, with
      the ability to detect gamma interferon spot-forming cells (SFC) in the range of
      10 to 1,000 SFC per million peripheral blood mononuclear cells (PBMCs). This
      assay has been validated by demonstrating the following: (i) the response
      detected is mediated almost entirely by CD4+ T cells, (ii) ELISPOT responses from
      fresh-frozen PBMCs are equivalent to those from freshly isolated cells, (iii)
      frozen PBMCs can be shipped on dry ice for up to 48 h without loss of activity,
      (iv) frozen PBMC samples can be stored in liquid nitrogen over long periods (>22
      months) without any significant change in response, and (v) the numbers of
      ELISPOTs counted using a computer-based imaging system are equivalent to those
      counted by humans but have lower variability. The ability to use frozen cells is
      facilitated by the use of a recombinant nuclease (Benzonase) that can prevent
      cell clumping when samples are thawed. Frozen PBMC samples can be cycled through
      multiple changes in storage between liquid nitrogen and dry ice without any
      change in response being detected. This facilitates collection of samples at one
      site and testing performed at a remote location. This VZV ELISPOT assay provides
      a new versatile tool for monitoring cellular immune responses either during a
      herpes zoster disease outbreak or following vaccination.

PMID- 11527796
TI  - Human lymphocyte proliferation responses following primary immunization with
      rabies vaccine as neoantigen.
AB  - Evaluation of the T-cell immune response following primary antigenic challenge
      with a neoantigen is a critical aspect of assessment of the cellular immune
      response. While many antigens can be used to accurately assess in vitro T-cell
      proliferation to a recall antigen, only a few neoantigens have been tested for
      their capacities to measure T-cell responses in vitro to a primary immunization.
      Rabies vaccination is an excellent candidate for the testing of T-cell
      proliferation responses to a primary immunization because few individuals have
      been exposed to rabies virus antigens. In the present study 14 rabies vaccine
      naive, healthy adult volunteers were immunized against rabies virus, and T-cell
      proliferation and antibody responses were measured before and after vaccination.
      Optimal lymphocyte proliferation to soluble rabies virus antigen occurred after 8
      days in culture. The average level of uptake of tritiated thymidine
      postimmunization was 29,620 +/- 4,448 cpm, whereas preimmunization levels were
      12,660 +/- 3,448 cpm (P = 0.002). All individuals showed increases in rabies
      virus antibody titers from <0.05 to 5.59 +/- 1.64 IU/ml. The degree of
      proliferation to tetanus toxoid as a recall antigen was similar to the response
      to rabies virus antigen among the cohort. Due to high levels of preimmunization
      proliferation, four subjects failed to demonstrate a twofold increase in response
      to rabies virus antigen. The high levels of T-cell responses may be due to a
      viral superantigen effect in some individuals. Rabies vaccination offers a safe
      and effective means for measurement of both T- and B-cell immune responses to a
      neoantigen in healthy and immune suppressed individuals.

PMID- 11527797
TI  - Molecular investigation of transmission of human immunodeficiency virus type 1 in
      a criminal case.
AB  - Very few criminal cases involving human immunodeficiency virus type 1 (HIV-1)
      transmission have been described. We report on an HIV-1 transmission case with a
      child being infected by an HIV-1-positive man. The objective was to determine
      through molecular epidemiology and phylogenetic analyses whether HIV-1 from the
      HIV-1-positive man could be the source of infection in the HIV-1-positive child,
      as claimed by the authorities. We conducted genetic analysis of three different
      parts of the HIV-1 genome (gag, pol, and env) by PCR, direct-sequencing, and
      phylogenetic analyses. We used maximum likelihood, maximum parsimony, and
      neighbor-joining methods for the phylogenetic analyses to investigate whether the
      sequences from the man and the child were related. We found that the viral
      sequences from the man and the child formed separate clusters in all of the
      phylogenetic analyses compared to the local controls. A unique amino acid
      deletion was identified in the C2-V3-C3 region of the env gene in the virus from
      the man and the child. These results were used in the criminal court to elucidate
      whether the virus from the man was related to the virus from the child. In
      summary, the results from the phylogenetic analyses, the sequence distances
      between the virus from the man and the virus from the child, and the
      identification of the unique molecular fingerprint in the env gene together
      indicated that the virus from the man and the virus from the child were
      epidemiologically linked.

PMID- 11527798
TI  - Plasmodium vivax polymorphism in a clinical drug trial.
AB  - Data from a double-blind randomized clinical drug trial were analyzed to find the
      comparative responses of two antirelapse drugs, bulaquine and primaquine, against
      different relapsing forms of Plasmodium vivax infection. A 1-year follow-up study
      strongly suggests that the duration of preerythrocytic development of P. vivax is
      a polymorphic characteristic, exhibited by two strains of hypnozoites responsible
      for early and late manifestations after primary infection. Short-term relapses
      were significantly higher in the first half year than long-term relapses, and the
      reverse was true in the second half year. Clinical drug response data showed that
      the hypnozoites characterized for short-term relapse were not susceptible to
      either of the antirelapse drugs in the currently administered dose, whereas
      hypnozoites characterized for long incubation were significantly susceptible.

PMID- 11527799
TI  - Identification of the psaA gene, coding for pneumococcal surface adhesin A, in
      viridans group streptococci other than Streptococcus pneumoniae.
AB  - The gene encoding the pneumococcal surface adhesin A (PsaA) protein has been
      identified in three different viridans group streptococcal species. Comparative
      studies of the psaA gene identified in different pneumococcal isolates by
      sequencing PCR products showed a high degree of conservation among these strains.
      PsaA is encoded by an open reading frame of 930 bp. The analysis of this fragment
      in Streptococcus mitis, Streptococcus oralis, and Streptococcus anginosus strains
      revealed a sequence identity of 95, 94, and 90%, respectively, to the
      corresponding open reading frame of the previously reported Streptococcus
      pneumoniae serotype 6B strain. Our results confirm that psaA is present and
      detectable in heterologous bacterial species. The possible implications of these
      results for the suitability and potential use of PsaA in the identification and
      diagnosis of pneumococcal diseases are discussed.

PMID- 11527800
TI  - Clinical and serological follow-up of patients with human granulocytic
      ehrlichiosis in Slovenia.
AB  - An evaluation of the clinical outcome and the duration of the antibody response
      of patients with human granulocytic ehrlichiosis (HGE) was undertaken in
      Slovenia. Adult patients with a febrile illness occurring within 6 weeks of a
      tick bite were classified as having probable or confirmed HGE based on the
      outcome of serological or PCR testing. Thirty patients (median age, 44 years)
      were enrolled, and clinical evaluations and serum collection were undertaken at
      initial presentation and at 14 days, 6 to 8 weeks, and 3 to 4, 6, 12, 18, and 24
      months. An indirect immunofluorescence assay (IFA) was performed, and reciprocal
      titers of > or =128 were interpreted as positive. Patients presented a median of
      4 days after the onset of fever and were febrile for a median of 7.5 days; four
      (13.3%) received doxycycline. Seroconversion was observed in 3 of 30 (10.0%)
      patients, and 25 (83.3%) showed >4-fold change in antibody titer. PCR results
      were positive in 2 of 3 (66.7%) seronegative patients but in none of 27
      seropositive patients at the first presentation. IFA antibody titers of > or =128
      were found in 14 of 29 (48.3%), 17 of 30 (56.7%), 13 of 30 (43.4%), and 12 of 30
      (40.0%) patients 6, 12, 18, and 24 months after presentation, respectively.
      Patients reporting additional tick bites during the study had significantly
      higher antibody titers at most time points during follow-up. No long-term
      clinical consequences were found during follow-up.

PMID- 11527801
TI  - Simplified assay for measuring Toxoplasma gondii immunoglobulin G avidity.
AB  - A Toxoplasma gondii immunoglobulin G (IgG) avidity enzyme-linked immunosorbent
      assay (ELISA) was developed that combines the accuracy of assays based on end
      point titers and the relative ease of assays based on optical density values.
      Like published procedures, the new assay's avidity index (AI) was based on
      differential T. gondii-specific IgG reactivity in serum-treated wells washed with
      urea buffer versus that in wells washed with control buffer; unlike previous
      assays, however, the IgG reactivity was measured quantitatively using a standard
      curve. The assay was evaluated using 24 IgG-positive and IgM-positive sera
      collected within 5 months of the onset of symptoms (recent-infection group) and
      25 IgG-positive and IgM-negative sera (past-infection group). All sera in the
      recent-infection group exhibited AI values of <0.18, whereas all sera in the past
      infection group exhibited AI values of >0.27. The AI values of the recent
      infection group showed significant correlation with the number of days after the
      onset of symptoms. A subset of 16 sera (8 recent and 8 past) was tested using a
      commercially available T. gondii IgG avidity ELISA based on end point titration;
      the results of the two assays showed highly significant correlation (R(2) =
      0.9125). In addition, we confirmed and extended the findings of other
      investigators, showing that AI values calculated using optical density values,
      but not AI values calculated using quantitative IgG values, varied significantly
      depending on the serum dilution used. This new assay should facilitate the
      accurate measurement of T. gondii IgG avidity in a reference laboratory setting.

PMID- 11527802
TI  - Comparison of Chemicon SimulFluor direct fluorescent antibody staining with cell
      culture and shell vial direct immunoperoxidase staining for detection of herpes
      simplex virus and with cytospin direct immunofluorescence staining for detection
      of varicella-zoster virus.
AB  - A new rapid direct immunofluorescence assay, the SimulFluor direct fluorescent
      antibody (DFA) assay, which can simultaneously detect herpes simplex virus types
      1 and 2 (HSV-1 and -2) and varicella-zoster virus (VZV), was evaluated in
      comparison with our current standard procedures of (i) shell vial direct
      immunoperoxidase (shell vial IP) staining and cell culture for detection of HSV
      and (ii) cytospin DFA staining for VZV detection. A total of 517 vesicular, oral,
      genital, and skin lesion specimens were tested by all three procedures. For HSV
      detection, the SimulFluor DFA assay had an overall sensitivity, specificity,
      positive predictive value, and negative predictive value of 80.0, 98.3, 92.3, and
      95.1%, respectively, when compared to culture. Shell vial IP staining had a
      sensitivity, specificity, positive predictive value, and negative predictive
      value of 87.6, 100, 100, and 96.9%, respectively, when compared with cell
      culture. The SimulFluor DFA assay, however, offers same-day, 1.5-hours results
      versus a 1- to 2-day wait for shell vial IP staining results and a 1- to 6-day
      wait for culture results for HSV. For VZV detection SimulFluor DFA staining
      detected 27 positive specimens as compared to 31 by our standard cytospin DFA
      technique--a correlation of 87.1%. A positive SimulFluor reaction for VZV is
      indicated by yellow-gold fluorescence compared to the bright apple-green
      fluorescence observed by cytospin DFA staining. There is no difference in
      turnaround time between the two assays. The SimulFluor DFA assay is a rapid
      immunofluorescence assay that can detect 80% of the HSV-positive specimens and
      87% of the VZV-positive specimens with a 1.5-h turnaround time.

PMID- 11527803
TI  - Comparison of serologic assays for detection of antibodies against human
      herpesvirus 8.
AB  - Improvement of serologic assays for detection of antibodies against human
      herpesvirus 8 (HHV-8) is critical to better understand its epidemiology and
      biology. We produced the HHV-8 latent (ORF73) and lytic (ORF65, K8.1, and
      glycoprotein B) antigens in the Semliki Forest virus system and evaluated their
      performance in immunofluorescence assays (IFAs) and enzyme-linked immunosorbent
      assays (ELISAs). These assays were compared with other latent antigen-based
      assays, including an IFA based on primary effusion lymphoma (PEL) cells and an
      ELISA based on bacterially expressed ORF73 antigen, as well as with other lytic
      antigen-based assays, including an IFA based on induced PEL cells, a commercial
      ELISA based on purified virions, and ELISAs based on K8.1- and ORF65-derived
      oligopeptides. We used a panel of 180 serum specimens obtained from three groups
      expected to have high, intermediate, and low HHV-8 prevalences. Using three
      different evaluation methods, we found that (i) the performances of the lytic
      antigen-based ELISAs were almost equivalent, (ii) the lytic antigen-based assays
      were more sensitive than the latent antigen-based assays, and (iii) in general,
      IFAs were more sensitive than ELISAs based on the same open reading frame. We
      also found that serum specimens from healthy individuals contained antibodies
      cross-reactive with HHV-8 glycoprotein B that can potentially cause false
      positive reactions in lytic PEL-based IFAs. Although this is not a substantial
      problem in most epidemiologic studies, it may confound the interpretation of data
      in studies that require high assay specificity. Because the K8.1-based IFA
      provides sensitivity similar to that of lytic PEL-based IFAs and improved
      specificity, it can be a useful alternative to the PEL-based IFAs.

PMID- 11527804
TI  - New coupled-particle light-scattering assay for detection of Ro/SSA (52 and 60
      kilodaltons) and La/SSB autoantibodies in connective tissue diseases.
AB  - The diagnostic and analytical performance of the coupled-particle light
      scattering assay in detecting anti-Ro/SSA autoantibodies (the 60-kDa [Ro60] and
      the 52-kDa [Ro52] antibodies) and anti-La/SSB autoantibodies was evaluated. The
      antigens were obtained by recombinant DNA procedures to include the most
      immunogenic epitopes for each protein by using a prokaryotic expression system.
      Serum samples from 151 patients with connective tissue diseases and 52 control
      subjects (including patients with viral infections, patients with Lyme disease,
      and healthy subjects) were studied. Sensitivities for detection of anti-Ro/SSA
      and anti-La/SSB were 88.2 and 95.2%, respectively; specificities were 97.6 and
      98.1%, respectively. The intra-assay coefficient of variation (CV) ranged from
      4.3 to 10.9% for anti-Ro/SSA and from 2.8 to 12.5% for anti-La/SSB; interassay
      CVs ranged from 6.5 to 13.2% and from 8.2 to 14.5%, respectively. Among the anti
      Ro/SSA-positive samples, Ro60 was recognized by 66% of the test sera and Ro52 was
      recognized by 95% of the test sera. Thirty-four percent of the Ro/SSA-positive
      sera were reactive only with the Ro52 antigen, indicating that anti-Ro52 is the
      most common antibody specificity recognized by anti-Ro/SSA autoantibodies. No
      differences were found between the prevalences of anti-Ro60 and anti-Ro52 in
      relation to systemic lupus erythematosus or Sjogren's syndrome. The results of
      the present study indicate that this new immunoassay is an efficient diagnostic
      tool for the detection of anti-Ro/SSA and anti-La/SSB antibodies in patients with
      autoimmune disorders.

PMID- 11527805
TI  - Maturational changes in peripheral lymphocyte subsets pertinent to monitoring
      human immunodeficiency virus-infected Chinese pediatric patients.
AB  - On the basis of results of testing of 212 peripheral blood samples from ethnic
      Chinese individuals in five age groups, ranging from birth to adulthood, by
      standardized flow cytometry techniques, we studied the maturational processes
      that are pertinent to monitoring the human immunodeficiency virus (HIV)-infected
      Chinese pediatric population. While the numbers of peripheral total white cells
      and percent lymphocytes declined from birth to adulthood, the percent CD3+ T
      lymphocytes was steady among all age groups studied. The numbers of CD3+ CD4+ (T
      helper) cells decreased markedly after the first year of life, followed by a
      slower decline afterward and then a slight increase before adulthood. The trend
      for CD3+ CD8+(T-suppressor) cells, however, was an increase among individuals of
      all age ranges. The numbers of CD19+ CD3- (B cells) increased only during the
      first year of life and then declined steadily, while natural killer (NK) cells
      showed the opposite pattern. Comparison of the results with those of studies done
      with a Caucasian population showed that both peripheral T-helper and T-suppressor
      cell numbers were low after the first year of life in the Chinese pediatric
      population in comparison with those in a Caucasian pediatric population. Lower B
      cell counts and higher NK-cell counts were seen after the first year of life in
      the Chinese population than in the Caucasian population. It is important that for
      each HIV-infected population normative ranges of the lymphocyte subset be
      established to monitor HIV-infected pediatric patients.

PMID- 11527806
TI  - Slow human immunodeficiency virus (HIV) infectivity correlated with low HIV
      coreceptor levels.
AB  - The absolute number of CD4+ lymphocytes in blood is prognostic for disease
      progression, yet the cell surface density of CD4 receptors or chemokine receptors
      on a single cell has not previously been found to be predictive of human
      immunodeficiency virus (HIV) infectivity outcome. It has recently been shown that
      human leukocyte elastase (HLE) and its ligand alpha(1) proteinase inhibitor
      (alpha(1)PI; alpha(1)antitrypsin) act as HIV fusion cofactors. The present study
      shows that decreased HIV infectivity is significantly correlated with decreased
      cell surface density of HLE but not with decreased CD4 nor chemokine receptors.
      In vitro HIV infectivity outcome in this study was predicted by the surface
      density of HLE on mononuclear phagocytes but not on lymphocytes. The set point
      HLE surface density was in part determined by alpha(1)PI. Decreased circulating
      alpha(1)PI was correlated with increased cell surface HLE and with increased HIV
      infectivity. The correlation of HIV infectivity outcome with surface HLE and
      circulating alpha(1)PI supports the utility of these HIV cofactors in diagnostic
      analysis and therapeutic intervention.

PMID- 11527807
TI  - Self antigen prognostic for human immunodeficiency virus disease progression.
AB  - We have recently found that an extracellular protein, alpha(1) proteinase
      inhibitor (alpha(1)PI; alpha(1) antitrypsin), is required for in vitro human
      immunodeficiency virus (HIV) infectivity outcome. We show here in a study of HIV
      seropositive patients that decreased viral load is significantly correlated with
      decreased circulating alpha(1)PI. In the asymptomatic category of HIV disease,
      100% of patients manifest deficient levels of active alpha(1)PI, a condition
      known to lead to degenerative lung diseases and a dramatically reduced life span.
      Further, HIV-associated alpha(1)PI deficiency is correlated with circulating anti
      alpha(1)PI immunoglobulin G. These results suggest that preventing HIV-associated
      alpha(1)PI deficiency may provide a strategic target for preventing HIV
      associated pathophysiology.

PMID- 11527808
TI  - Highly active antiretroviral therapy in human immunodeficiency virus type 1
      infected children: analysis of cellular immune responses.
AB  - The present study analyzes the effect of highly active antiretroviral therapy
      (HAART) on restoration of cellular immunity in human immunodeficiency virus (HIV)
      infected children over a 24-week period following initiation of HAART with
      ritonavir, nevirapine, and stavudine. The immunological parameters evaluated at
      four time points (at enrollment and at 4, 12, and 24 weeks of therapy) included
      cytokine production by monocytes as well as T-cell proliferation in response to
      mitogen, alloantigen, and recall antigens including HIV type 1 envelope peptides.
      Circulating levels of interleukin-16 (IL-16) were measured, in addition to CD4+ T
      cell counts, plasma HIV RNA levels, and the delayed-type hypersensitivity (DTH)
      response. At enrollment the children exhibited defects in several immune
      parameters measured. Therapy increased CD4+ T-cell counts and decreased viral
      loads significantly. By contrast, the only immunological parameter that was
      significantly increased was IL-12 p70 production by monocytes; the DTH response
      to Candida albicans also showed a strong increase in patients becoming positive.
      In conclusion, these results demonstrate that HAART in HIV-infected children
      affects the dynamics of HIV replication and the CD4+ T-cell count over 24 weeks,
      similar to the pattern seen in HIV-infected adults. Furthermore, these data
      indicate improvement in antigen-presenting cell immunological function in HIV
      infected children induced by HAART.

PMID- 11527809
TI  - V gamma 9V delta 2 T cells in human legionellosis.
AB  - In humans, expansion of circulating Vgamma9Vdelta2 T cells seems to be a
      pathophysiological denominator shared by protozoan and intracellular bacterial
      diseases. The assumption was tested here on legionellosis, a condition conforming
      to the category but not yet described with respect to gammadelta T cells. Levels
      of Vgamma9Vdelta2 T cells in peripheral blood were measured at various intervals
      in 14 subjects undergoing a Pontiac fever-like disease, shown by serological
      investigation to be caused by Legionella micdadei. In samples obtained 4 to 6
      days after the onset of the disease, the mean percentage (+/- the standard
      deviation) of Vgamma9Vdelta2+ T cells among CD3+ cells was 1.0% +/- 0.5%,
      compared to 5.0% +/- 3.9% in healthy control subjects (P < 0.001). Thereafter, a
      pronounced increase occurred and at 2 to 7 weeks after onset, mean peak levels
      were as high as approximately equal to 15%. During the next 6 months, values
      slowly declined, although without reaching the normal range. Percentages of
      gammadelta+ T cells expressing tumor necrosis factor alpha or gamma interferon in
      response to phorbol myristate acetate were assayed in vitro. At 14 to 16 days
      after the onset of disease, the expression of both cytokines was increased (P <
      0.01), whereas at 5 to 7 weeks, the expression of tumor necrosis factor alpha was
      decreased (P < 0.05), possibly reflecting modulation of an inflammatory response.
      In conclusion, Pontiac fever was found to be associated with a pronounced and
      long-lasting expansion of Vgamma9Vdelta2 T cells, implying that the subset may
      also be pathophysiologically important in a mild and transient form of
      intracellular bacterial diseases. Surprisingly, the expansion was preceded by a
      depletion of circulatory Vgamma9Vdelta2 T cells. Possibly, Vgamma9Vdelta2 T cells
      are initially recruited to a site of infection before they expand in response to
      antigen and occur in high numbers in blood.

PMID- 11527810
TI  - Detection of Y chromosome DNA as evidence of semen in cervicovaginal secretions
      of sexually active women.
AB  - The detection of traces of semen in cervicovaginal secretions (CVS) from sexually
      active women practicing unprotected sex is a prerequisite for the accurate study
      of cervicovaginal immunity. Two semen markers, the prostatic-specific antigen
      (PSA) and the Y chromosome, were detected in parallel in CVS obtained by a
      standardized vaginal washing of consecutive women attending the principal medical
      center for sexually transmitted diseases of Bangui, Central African Republic. PSA
      was detected by immunoenzymatic capture assay in the cell-free fraction of CVS,
      and the Y chromosome was detected by a single PCR assay of DNA extracted by
      silica from the cell fraction (Y PCR). Fifty (19%) cell-free fractions of the 264
      beta-globin-positive CVS samples were positive for PSA, and 100 (38%) cell
      fractions of the CVS samples were positive for the Y chromosome. All the 50 (19%)
      PSA-containing CVS samples were also positive for the Y chromosome. Fifty (19%)
      CVS samples were positive only for the Y chromosome, with no detectable PSA. The
      remaining 164 (62%) CVS samples were both PSA and Y chromosome negative. These
      findings demonstrate that CVS from sexually active women may contain cell
      associated semen residues unrecognized by conventional immunoenzymatic assays
      used to detect semen components. The detection of cell-associated male DNA with a
      highly sensitive and specific procedure such as Y PCR constitutes a method of
      choice to detect semen traces in female genital secretions.

PMID- 11527812
TI  - Chemokine receptor CCR5 Delta 32 genetic analysis using multiple specimen types
      and the NucliSens Basic Kit.
AB  - Resistance to HIV-1 infection and delayed disease progression have been
      associated with a 32-bp deletion (Delta32) in the gene encoding the CCR5
      chemokine receptor. In the present study we describe the modification of a
      nucleic acid sequence-based amplification (NASBA)-based CCR5 genotyping assay for
      a NucliSens Basic Kit (Organon Teknika, Durham, N.C.) format using a new target
      specific sandwich oligonucleotide detection methodology. The new method permitted
      the use of generic electrochemiluminescent probes supplied in the NucliSens Basic
      Kit, whereas the original NASBA method required expensive target-specific
      ruthenium detection probes. The Basic Kit CCR5 Delta32 genotypic analysis was in
      100% concordance with both the original NASBA assay and DNA PCR results. This
      study also evaluated the use of multiple specimen types, including peripheral
      blood mononuclear cells (PBMC), whole blood, dried blood spots, buccal scrapings,
      and plasma, for CCR5 genotype analysis. The sensitivities of the three assays
      were comparable when PBMC or whole blood was the specimen source. In contrast,
      when dried blood spots, buccal scrapings, or plasma was used as the sample
      source, the sensitivity of DNA PCR was 80.95, 42.8, or 0%, respectively, compared
      to 100% sensitivity obtained with the original NASBA and Basic Kit NASBA assays.
      Our study indicates that the NucliSens Basic Kit NASBA assay is very sensitive
      and specific for CCR5 Delta32 genotyping using multiple sample types.

PMID- 11527811
TI  - Toxin genes and other characteristics of Staphylococcus aureus isolates from milk
      of cows with mastitis.
AB  - In the present study, 103 Staphylococcus aureus strains isolated from milk
      samples from 60 cows with mastitis from eight different farms in seven different
      locations in one region of Germany were compared pheno- and genotypically and by
      identification of various toxins. On the basis of culture and hemolytic
      properties and by determination of the tube coagulase reaction, all of the
      isolates could be identified as S. aureus. This could be confirmed by PCR
      amplification of species-specific parts of the gene encoding the 23S rRNA. In
      addition, all of the S. aureus isolates harbored the genes encoding
      staphylococcal coagulase and clumping factor and the genes encoding the X region
      and the immunoglobulin G binding region of protein A. These four genes displayed
      size polymorphisms. By PCR amplification, the genes for the toxins staphylococcal
      enterotoxin A (SEA), SEC, SED, SEG, SEI, SEJ, and TSST-1 but not those for SEB,
      SEE, SEH, and the exfoliative toxins ETA and ETB could be detected. To analyze
      the epidemiological relationships, the isolates were subjected to DNA
      fingerprinting by macrorestriction analysis of their chromosomal DNAs. According
      to the observed gene polymorphisms, the toxin patterns, and the information given
      by macrorestriction analysis of the isolates by pulsed-field gel electrophoresis,
      a limited number of clones seemed to be responsible for the cases of bovine
      mastitis on the various farms.

PMID- 11527813
TI  - Lipoteichoic acid inhibits interleukin-2 (IL-2) function by direct binding to IL
      2.
AB  - Lipoteichoic acid (LTA) is associated with the cell envelope of most gram
      positive bacteria. Although previously thought to act mainly as a virulence
      factor by virtue of its adhesive nature, evidence is now provided that LTA can
      also suppress the function of interleukin-2 (IL-2), an autocrine growth factor
      for T cells. LTA from four separate bacterial strains lowered the levels of
      detectable IL-2 during a peripheral blood mononuclear cell response to the
      antigen tetanus toxoid (TT). T-cell proliferation in response to TT was similarly
      inhibited by LTA. In contrast, levels of detectable gamma interferon increased.
      In addition, LTA inhibited IL-2 detection by enzyme-linked immunosorbent assay
      (ELISA) and blocked the proliferative response of an IL-2-dependent T-cell line
      to soluble IL-2. Further studies using ELISA demonstrated that LTA blocks IL-2
      detection and function by binding directly to IL-2. Flow cytometric analysis
      revealed that IL-2 binding to T cells is inhibited in the presence of purified
      LTA but not LTA plus anti-LTA monoclonal antibody. In summary, these studies
      demonstrate a novel effect of LTA on the immune response through direct binding
      to IL-2 and inhibition of IL-2 function. Importantly, gram-positive organisms
      from which LTA is obtained not only play an important role in the pathology of
      diseases such as bacterial endocarditis, septic shock, acute respiratory distress
      syndrome, and multiple organ failure but also comprise a significant portion of
      commensal populations within the human host. Inhibition of IL-2 function by LTA
      may represent yet another mechanism by which gram-positive bacteria dampen the
      host immune response and facilitate survival. Thus, LTA provides a potential
      target for therapeutic intervention when gram-positive organisms are involved.

PMID- 11527814
TI  - Late hematogenous infection of subcutaneous implants in rats.
AB  - Late biomaterial-centered infection is a major complication associated with the
      use of biomaterial implants. In this study biomaterials that had been implanted
      subcutaneously in rats were hematogenously challenged with bacteria 4 weeks after
      implantation. Bacteria were spread either by intravenous injection or by
      stimulation of bacterial translocation. It was found that none of the
      biomaterials was infected by hematogenous spread, whereas 5% of the implants were
      infected by perioperative contamination. We conclude that late hematogenous
      infection of subcutaneous biomaterials does not occur in the rat. For humans as
      well, there are growing doubts whether implants actually become infected through
      hematogenous routes; it is thought that late infections may be caused by delayed
      appearance of perioperatively introduced bacteria.

PMID- 11527816
TI  - Anti-CD20 monoclonal antibody treatment of human herpesvirus 8-associated, body
      cavity-based lymphoma with an unusual phenotype in a human immunodeficiency virus
      negative patient.
AB  - Human herpesvirus 8 (HHV-8), or Kaposi's sarcoma-associated herpesvirus, is a
      gammaherpesvirus first detected in Kaposi's sarcoma tumor cells and subsequently
      in primary effusion lymphoma (PEL) tumor cells and peripheral blood mononuclear
      cells from PEL patients. PEL has been recognized as an individual nosologic
      entity based on its distinctive features and consistent association with HHV-8
      infection. PEL is an unusual form of body cavity-based B-cell lymphoma (BCBL). It
      occurs predominantly in human immunodeficiency virus (HIV)-positive patients but
      occasionally also in elderly HIV-negative patients. We describe a case of PEL,
      with ascites, bilateral pleural effusions, and a small axillary lymphadenopathy,
      in a 72-year-old HIV-negative man. PCR performed on a lymph node specimen and in
      liquid effusion was positive for HHV-8 and negative for Epstein-Barr virus. The
      immunophenotype of the neoplastic cells was B CD19+ CD20+ CD22+ with coexpression
      of CD10 and CD23 and with clonal kappa light chain rearrangement. The patient was
      treated with Rituximab, a chimeric (human-mouse) anti-CD20 monoclonal antibody.
      Thirteen months later, the patient continued in clinical remission. This is the
      first report of an HHV-8-associated BCBL in an HIV-negative patient in Argentina.

PMID- 11527817
TI  - Seroprevalence of antibodies to microorganisms known to cause arterial and
      myocardial damage in patients with or without coronary stenosis.
AB  - Infections are assumed to play a role in coronary artery disease (CAD) and
      cardiomyopathies. It is unknown whether the seroprevalence of antibodies to these
      microorganisms is higher in patients with than without CAD. The seroprevalence of
      antibodies to Bartonella henselae, Borrelia burgdorferi, Chlamydia pneumoniae,
      Coxiella burnetii, Helicobacter pylori, human granulocytic Ehrlichia, Leptospira,
      Rickettsia conorii, and Treponema pallidum was assessed prospectively in patients
      with exertional dyspnea or anginal chest pain who underwent coronary angiography
      because of suspected CAD. Patients with normal angiograms (NA) were those in whom
      no more than 50% stenosis of any coronary artery was found. Patients with CAD
      were patients who underwent percutaneous transluminal coronary angioplasty. There
      were 50 patients with CAD (9 female) and 62 with NA (25 female), with a mean age
      of 62 years. All patients had antibodies to at least one microorganism: to B.
      henselae, 8% of CAD patients and 5% of NA patients; to B. burgdorferi IgG, 14%
      CAD and 6% NA; to B. burgdorferi IgM, 6% CAD and 3% NA; to C. pneumoniae
      lipopolysaccharide (LPS) IgA, 76% CAD and 77% NA; to C. pneumoniae LPS IgG, 80%
      CAD and 90% NA; to C. burnetii, 0% CAD and 5% NA; to H. pylori, 92% CAD and 68%
      NA; to human granulocytic Ehrlichia, 8% CAD and 3% NA; to Leptospira IgG, 4% CAD
      and 2% NA; to R. conorii, 10% in both groups; and to T. pallidum, 2% CAD and 0%
      NA. The seroprevalence of antibodies to micro-organisms known to induce arterial
      and myocardial damage does not differ between patients with CAD and NA.

PMID- 11527815
TI  - Presence of oligoclonal T cells in cerebrospinal fluid of a child with
      multiphasic disseminated encephalomyelitis following hepatitis A virus infection.
AB  - We have investigated the clonality of beta-chain T-cell receptor (TCR)
      transcripts from the cerebrospinal fluid (CSF) and peripheral blood from a 7-year
      old child who developed a multiphasic disseminated encephalomyelitis following an
      infection with hepatitis A virus. We amplified beta-chain TCR transcripts by
      nonpalindromic adaptor (NPA)-PCR-Vbeta-specific PCR. TCR transcripts from only
      five Vbeta families (Vbeta13, Vbeta3, Vbeta17, Vbeta8, and Vbeta20) were detected
      in CSF. The amplified products were combined, cloned, and sequenced. Sequence
      analysis revealed in the CSF substantial proportions of identical beta-chain of
      TCR transcripts, demonstrating oligoclonal populations of T cells. Seventeen of
      35 (48%) transcripts were 100% identical, demonstrating a major Vbeta13.3
      Dbeta2.1 Jbeta1.3 clonal expansion. Six of 35 (17%) transcripts were also 100%
      identical, revealing a second Vbeta13 clonal expansion (Vbeta13.1 Dbeta2.1
      Jbeta1.2). Clonal expansions were also found within the Vbeta3 family (transcript
      Vbeta3.1 Dbeta2.1 Jbeta1.5 accounted for 5 of 35 transcripts [14%]) and within
      the Vbeta20 family (transcript Vbeta20.1 Dbeta1.1 Jbeta2.4 accounted for 3 of 35
      transcripts [8%]). These results demonstrate the presence of T-cell oligoclonal
      expansions in the CSF of this patient following infection with hepatitis A virus.
      Analysis of the CDR3 motifs revealed that two of the clonally expanded T-cell
      clones exhibited substantial homology to myelin basic protein-reactive T-cell
      clones. In contrast, all Vbeta TCR families were expressed in peripheral blood
      lymphocytes. Oligoclonal expansions of T cells were not detected in the
      peripheral blood of this patient. It remains to be determined whether these
      clonally expanded T cells are specific for hepatitis A viral antigen(s) or host
      central nervous system antigen(s) and whether molecular mimicry between hepatitis
      A viral protein and a host protein is responsible for demyelinating disease in
      this patient.

PMID- 11527819
TI  - Serum antibody response to polysaccharides in children with recurrent respiratory
      tract infections.
AB  - We evaluated children (15-months old and older) with recurrent upper respiratory
      tract infections and normal levels of immunoglobulins in serum for specific
      polysaccharide immunodeficiency using an enzyme-linked immunosorbent assay
      method. Results showed that of 12 patients vaccinated with Act-HIB vaccine, one
      did not develop specific antibodies to Haemophilus influenzae type b,
      demonstrating that such immunodeficiency is present in Costa Rican children.

PMID- 11527818
TI  - Effects of calorie restriction on polymicrobial peritonitis induced by cecum
      ligation and puncture in young C57BL/6 mice.
AB  - Calorie restriction (CR) is known to prolong the life span and maintain an active
      immune function in aged mice, but it is still not known if rodents under CR can
      respond optimally to bacterial infection. We report here on the influence of CR
      on the response of peritoneal macrophages to lipopolysaccharide, splenic NF
      kappaB and NF-interleukin-6 (IL-6) activities, and mortality in polymicrobial
      sepsis induced by cecal ligation and puncture (CLP). Macrophages from 6-month-old
      C57BL/6 mice on a calorie-restricted diet were less responsive to
      lipopolysaccharide, as evidenced by lower levels of IL-12 and IL-6 protein and
      mRNA expression. Furthermore, in vitro lipopolysaccharide-stimulated macrophages
      from mice under CR also expressed decreased lipopolysaccharide receptor CD14
      levels as well as Toll-like receptor 2 (TLR2) and TLR4 mRNA levels. In addition,
      the phagocytic capacity and class II (I-A(b)) expression of macrophages were also
      found to be significantly lower in mice under CR. Mice under CR died earlier (P <
      0.005) after sepsis induced by CLP, which appeared to be a result of increased
      levels in serum of the proinflammatory cytokines tumor necrosis factor alpha and
      IL-6 and splenic NF-kappaB and NF-IL-6 activation 4 h after CLP. However, mice
      under CR survived significantly (P < 0.005) longer than mice fed ad libitum when
      injected with paraquat, a free radical-inducing agent. These data suggest that
      young mice under CR may be protected against oxidative stress but may have
      delayed maturation of macrophage function and increased susceptibility to
      bacterial infection.

PMID- 11527820
TI  - Serum immunoglobulin G antibody responses to Bordetella pertussis
      lipooligosaccharide and B. parapertussis lipopolysaccharide in children with
      pertussis and parapertussis.
AB  - Serum immunoglobulin G (IgG) antibodies against the lipooligosaccharide (LOS) of
      Bordetella pertussis and the lipopolysaccharide (LPS) of Bordetella parapertussis
      were measured by enzyme-linked immunosorbent assay in paired sera from 40
      children with pertussis and 14 with parapertussis. Wide differences in the
      individual responses were noted. Both anti-LOS and -LPS IgG levels increased
      significantly in the children with pertussis, as did anti-LPS but not anti-LOS in
      those with parapertussis.

PMID- 11527821
TI  - Determination of human immunodeficiency virus type 1 subtypes by a rapid method
      useful for the routine diagnostic laboratory.
AB  - The existence of human immunodeficiency virus type 1 (HIV-1) subtypes has many
      important implications for the global evolution of HIV and for the evaluation of
      pathogenicity, transmissibility, and candidate HIV vaccines. The aim of this
      study was to establish a rapid method for determination of HIV-1 subtypes useful
      for a routine diagnostic laboratory and to investigate the distribution of HIV-1
      subtypes in Austrian patients. Samples were tested by a subtyping method based on
      a 1.3-kb sequence of the polymerase gene generated by a commercially available
      drug resistance assay. The generated sequence was subtyped by means of an HIV
      sequence database. Results of 74 routine samples revealed subtype B (71.6%) as
      the predominant subtype, followed by subtype A (13.5%) and subtype C (6.8%).
      Subtypes E, F, G, and AE (CM240) were also detected. This subtyping method was
      found to be very easy to handle, rapid, and inexpensive and has proved suitable
      for high-throughput routine diagnostic laboratories. The specific polymerase gene
      sequence, however, must be existent.

PMID- 11527822
TI  - Expression of natural peptide antibiotics in human articular cartilage and
      synovial membrane.
AB  - In view of frequent present use of invasive procedures on limb joints, it is
      astonishing that articular joint inflammation is a rare event. We questioned
      whether antimicrobial peptides play a role in protecting human articular
      cartilage and synovial membrane against inflammatory agents. Our results
      implicate defensins in the protection of human articular joints against
      pathogens.

PMID- 11527823
TI  - Excretory-secretory antigens of Trypanosoma cruzi are potentially useful for
      serodiagnosis of chronic Chagas' disease.
AB  - The reactivities of sera from chronic chagasic patients against the
      trypomastigote excreted-secreted antigens (TESA) of Trypanosoma cruzi strains
      with different biodemes were analyzed by TESA-blot and TESA-enzyme-linked
      immunosorbent assay (ELISA). Although both tests presented high sensitivity and
      specificity, TESA-ELISA is more appropriate for screening a larger number of
      samples.

PMID- 11527824
TI  - Significant role of interleukin-8 in pathogenesis of pulmonary disease due to
      Mycoplasma pneumoniae infection.
AB  - We found elevated levels of interleukin-8 in pleural fluid samples from patients
      with pleural effusion and with a sustained fibrotic change of the lung due to
      Mycoplasma pneumoniae infection. This result suggests a critical role of
      interleukin-8 in the pathogenesis of a certain type of pulmonary disease caused
      by M. pneumoniae.

PMID- 11527825
TI  - Reactivity of MEST-1 (antigalactofuranose) with Trypanosoma cruzi
      glycosylinositol phosphorylceramides (GIPCs): immunolocalization of GIPCs in
      acidic vesicles of epimastigotes.
AB  - Using confocal microscopy, MEST-1-positive immunofluorescence was observed within
      various Trypanosoma cruzi forms, except in cell-derived trypomastigotes.
      Glycosylinositol phosphorylceramides were identified by thin-layer chromatography
      immunostaining as the antigens recognized by MEST-1 in these parasites. In
      epimastigotes, labeling of MEST-1 coincided with acidic vesicles, indicating an
      internal localization of these glycoconjugates.

PMID- 11527826
TI  - High serum interleukin-10 and tumor necrosis factor alpha levels in chronic
      paracoccidioidomycosis.
AB  - In patients with chronic paracoccidioidomycosis (n = 10), levels of tumor
      necrosis factor alpha, interleukin-10, and interleukin-2 in serum, measured by
      enzyme-linked immunosorbent assay (in picograms per milliliter, as mean +/-
      standard error of the mean), were higher than in normal controls (n = 8): 186 +/-
      40 versus 40 +/- 7 (P < 0.05), 203 +/- 95 versus 20 +/- 8 (P = 0.001), and 96.3
      +/- 78.57 versus 1.19 +/- 1.19 (P = 0.045), respectively. Gamma interferon and
      interleukin-4 levels were similar in patients and controls.

PMID- 11527829
TI  - Should physicians routinely inquire about guns? Yes: inquiry could save lives.

PMID- 11527830
TI  - Should physicians routinely inquire about guns? No: this inquiry is an invasion
      of privacy.

PMID- 11527831
TI  - When does primary care turn into palliative care?

PMID- 11527834
TI  - Why global health matters to US primary care physicians.

PMID- 11527832
TI  - Physicians' legal duty to relieve suffering.

PMID- 11527835
TI  - The critical issues in global health today.

PMID- 11527837
TI  - Use of Neo-melubrina, a banned antipyretic drug, in San Diego, California: a
      survey of patients and providers.
AB  - BACKGROUND: Dipyrone is an antipyretic drug that has been associated with
      agranulocytosis. It is banned in the United States but is available in Mexico
      under the name Neo-melubrina. OBJECTIVES: To define the use of Neo-melubrina in
      the Hispanic population of 2 San Diego, California, community clinics and to
      determine local physicians' and nurse practitioners' awareness of the drug and
      its risks. DESIGN: Patient survey and provider survey. PARTICIPANTS:  PATIENTS:
      200 parents of Hispanic pediatric patients. Providers: members of San Diego
      chapters of the American Academy of Pediatrics, the American Academy of Family
      Physicians, and the California Coalition of Nurse Practitioners. MAIN OUTCOME
      MEASURES: Self-reported use of Neo-melubrina by patients, and provider awareness
      of Neo-melubrina and its most significant side effects. RESULTS: Of the 200
      patients, 76 (38.0%) reported a lifetime use of Neo-melubrina. Most (56%) used it
      for both pain and fever. Most providers were unable to correctly identify why Neo
      melubrina might be used or its adverse effects. Physicians answered correctly
      more often than nurse practitioners and pediatric providers more often than
      family medicine providers. Providers who trained within 75 miles of the US-Mexico
      border, who reported a patient population of more than 50% Hispanic, and who were
      resident physicians at the time of the survey were most likely to answer
      correctly. CONCLUSIONS: Neo-melubrina has been used by a substantial percentage
      of Hispanic patients in the community clinics surveyed. Many San Diego health
      care providers are unaware of this medication and may, therefore, miss
      opportunities to educate patients about safer alternatives.

PMID- 11527839
TI  - We should always ask our patients about unconventional treatments.

PMID- 11527840
TI  - Does a fixed physician reminder system improve the care of patients with coronary
      artery disease? A randomized controlled trial.

PMID- 11527842
TI  - Changing physician behavior: what does it take?

PMID- 11527843
TI  - Why should primary care physicians know about breast cancer genetics?

PMID- 11527845
TI  - Dialog on genetic catastrophe.

PMID- 11527850
TI  - Seizure disorders: Part 2. Treatment.

PMID- 11527851
TI  - Attention deficit hyperactivity disorder.

PMID- 11527853
TI  - Treating dyspnea in a patient with advanced chronic obstructive pulmonary
      disease.

PMID- 11527852
TI  - Methemoglobinemia.

PMID- 11527855
TI  - Myth: silver sulfadiazine is the best treatment for minor burns.

PMID- 11527858
TI  - Immigrant women's health: Infectious diseases--Part 1. Clinical assessment,
      tuberculosis, hepatitis, and malaria.

PMID- 11527859
TI  - Prompting patients when taking a history may reduce error.

PMID- 11527860
TI  - Ignoring the elephant.

PMID- 11527861
TI  - Culture and one child's genetic abnormality.

PMID- 11527862
TI  - Community participation in health: perpetual allure, persistent challenge.
AB  - The concept of community participation continues to capture the attention of
      international health policymakers and analysts nearly a quarter of a century
      after it was formally introduced at the Alma Ata Conference. This paper reviews
      trends in the participation literature of the 1990s, drawing examples primarily
      from Latin America. The following topics are discussed: sustainability, new
      methods for operationalizing and evaluating participation, the significance of
      local and cultural variability in determining outcomes, participatory self
      determination as raised in the social movements literature, the increasing
      importance of intersectoral linkages, and continuing impediments posed by
      biomedical ideologies and systems. While the rhetoric and practice of
      participation have become fully integrated into mainstream health and development
      discourses, the paper concludes that ideological and political disagreements
      continue to divide pragmatists, who favour utilitarian models of participation,
      from activists, who prefer empowerment models.

PMID- 11527863
TI  - The performance of social marketing in reaching the poor and vulnerable in AIDS
      control programmes.
AB  - The article reviews evidence on the impact and effectiveness of condom social
      marketing programmes (CSMPs) in reaching the poor and vulnerable with
      information, services and products in the context of HIV/AIDS/STD prevention and
      control. Ideally, the success of CSMPs would be judged by whether they contribute
      to sustained improvements in sexual health outcomes at the population level.
      Given methodological and attribution difficulties, intermediary criteria are
      employed to assess effectiveness and impact, focusing on changes in behaviour
      (including condom use) among poor and vulnerable groups, and access by the poor
      and vulnerable to condoms, services and information. It remains difficult to
      reach definitive conclusions about the extent to which CSMPs meet the sexual
      health needs of the poor and vulnerable, due largely to reliance on sales data
      for CSMP monitoring and evaluation. CSMPs (like many health programme strategies)
      have traditionally collected little information on client profiles, health
      seeking behaviour, condom use effectiveness, and supply-side issues. Recent data
      indicate that CSMPs are unlikely to be pro-poor in their early stages, in terms
      of the distribution of benefits, but as CSMPs mature, then inequities in access
      diminish, followed by reduced inequities in condom use. The paper assesses the
      extent to which social marketing is effective in improving access for the poor
      and vulnerable using a number of variables. In terms of economic access, it is
      evident that low-income groups are particularly sensitive to CSMP price
      increases, and that a cost-recovery focus excludes the poorest. Convenience is
      significantly improved for those who can afford to pay, and CSMPs appear to be
      addressing social and regulatory constraints to access. Conventional CSMP
      monitoring systems make it difficult to assess the effectiveness of behavioural
      change IEC strategies, although data on this dimension of the social marketing
      approach are beginning to emerge.

PMID- 11527864
TI  - Scaling-up HIV/AIDS and TB home-based care: lessons from Zambia.
AB  - Home-based care coverage in Africa is currently very low and likely to reduce
      drastically in the near future. This paper investigates the low coverage of home
      based care programmes in Africa and uses two home-based care projects in Zambia
      as case studies. The very limited involvement of governments in the provision of
      home-based care services appears to be one of the main reasons behind the low
      coverage of home-based care in Africa. Governments therefore should provide some
      form of basic home-based care services and/or strengthen support to other
      institutions providing home-based care. In order to facilitate governments'
      involvement in home-based care activities, an analysis of tasks performed by
      community nurses and volunteers is used to identify tasks that government,
      missionary or NGO employed nurses may be able to provide without, or with very
      limited, donor assistance. However, further research and development is needed to
      develop affordable, feasible and sustainable home care programmes that can be
      implemented by staff working in government, NGO and missionary health facilities.
      In addition, innovative strategies are required to establish effective
      partnerships between the NGO, missionary and government health facilities.

PMID- 11527865
TI  - Assessing a computerized routine health information system in Mali using LQAS.
AB  - BACKGROUND: Between 1987 and 1998 Save the Children conducted a child survival
      programme in Mali with the goal of reducing maternal and child morbidity and
      mortality. An integral part of this programme was a computerized demographic
      surveillance and health information system (HIS) that gathered data on
      individuals on an on-going basis. OBJECTIVE: To assess the overall coverage and
      quality of the data in the HIS, to identify specific health districts that needed
      improvements in data collection methods, and to determine particular areas of
      weakness in data collection. METHODS: Random samples of 20 mothers with children
      <5 years were selected in each of 14 health districts. Mothers were interviewed
      about pregnancies, live births, deaths of children <5, and children's growth
      monitoring and immunization status. The Lot Quality Assurance Method (LQAS) was
      used to identify districts in which records and interview results did not meet
      predetermined levels of acceptability. Data collected in the interviews were
      combined to estimate overall coverage and quality. RESULTS: When all variables
      were analyzed, all 14 lots were rejected, and it was estimated that 52% of all
      events occurring in the community were registered in ProMIS. Much of this poor
      performance was due to immunization and growth monitoring data, which were not
      updated due to printer problems. Coverage of events increased (92%) when
      immunizations and growth monitoring were excluded, and no lots were rejected.
      When all variables were analyzed for quality of data recorded, six lots were
      rejected and the overall estimation was 83%. With immunizations and growth
      monitoring excluded, overall quality was 86% and no lots were rejected.
      CONCLUSIONS: The comprehensive computerized HIS did not meet expectations. This
      may be due, in part, to the ambitious objective of complete and intensive
      monitoring of a large population without adequate staff and equipment. Future
      efforts should consider employing a more targeted and streamlined HIS so that
      data can be more complete and useful.

PMID- 11527866
TI  - Safer maternal health in rural Uttar Pradesh: do primary health services
      contribute?
AB  - India accounts for about one-quarter of maternal deaths world wide, with the most
      recent statistics showing an average maternal mortality ratio of 407 per 100 000
      live births at the national level. The government had hoped to reduce maternal
      mortality to 200 by 2000, but it is clear that this was not achieved. This paper
      explores the reasons why the most populous state of Uttar Pradesh continues to
      have one of the highest reported maternal mortality ratios in India. Data from
      two districts of Uttar Pradesh on mother and child health-care utilization and
      the readiness of the public sector to provide antenatal and emergency obstetric
      services are used to illustrate the reasons why maternal mortality has not
      declined. While blueprints for safe motherhood programmes exist, the equipment
      and technical competence to provide services is weak at the present moment.
      Reductions in maternal mortality would require interventions to improve service
      delivery as well as community mobilization to improve utilization of services,
      especially in life-threatening situations.

PMID- 11527868
TI  - The impact of supervision on stock management and adherence to treatment
      guidelines: a randomized controlled trial.
AB  - Ensuring the availability of essential drugs and using them appropriately are
      crucial if limited resources for health care are to be used optimally. While
      training of health workers throughout Zimbabwe in drug management (including
      stock management and rational drug use) resulted in significant improvements in a
      variety of drug use indicators, these achievements could not be sustained, and a
      new strategy was introduced based on the supervision of primary health care
      providers. This was launched in 1995 with a training course in supervisory skills
      for district pharmacy staff. In order to evaluate the impact of the supervision
      and the effectiveness of the training programme, adherence to standard treatment
      guidelines (STG) and stock management protocols was evaluated in a randomized
      controlled trial. The study compared three different groups of health facilities:
      those that received supervision for either use of STG (n = 23) or stock
      management (n = 21) - each facility acting as control for the other area of
      supervision - and a comparison group of facilities which received no supervision
      (n = 18). On-the-spot supervision by a specially trained pharmacy staff, based
      around identified deficiencies, took place at the start of the study and 3 months
      later. The evaluation compared performance on a variety of drug management
      indicators at baseline and 6-8 months after the second supervisory visit. The
      results of the study showed that, following supervision, overall stock management
      improved significantly when compared with the control and comparison groups.
      Similar improvements were demonstrated for adherence to STG, although the effect
      was confounded by other interventions. The study also showed that supervision has
      a positive effect on improving performance in areas other than those supervised,
      and demonstrated that pharmacy technicians with limited clinical skills can be
      trained to influence primary health care workers to positively improve
      prescribing practices. Allocating resources to supervision is likely to result in
      improved performance of health workers with regard to the rational use of
      essential drugs, resulting in improved efficiency and effectiveness.

PMID- 11527867
TI  - A cost-minimization approach to planning the geographical distribution of health
      facilities.
AB  - This paper illustrates a method of planning the geographic distribution of health
      facilities in order to maximize the social benefits achievable from the
      investment. Data from Bangladesh have been used to determine the optimal
      distribution of emergency obstetric care (EOC) facilities in the country using
      the estimates of average social cost per woman. Costs incurred by households,
      including the costs associated with maternal mortality, tend to increase with
      increasing radius of a facility's catchment area. The average facility-based
      costs tend to decline with increasing radius due to lower per capita capital
      expenditures. The summation of these two average cost functions generates a U
      shaped curve. In this research, the minimum point of the aggregated average cost
      curve defines the 'optimal' radius of a health facility. The catchment area
      defined by the optimal radius minimizes the average social cost of providing EOC
      services in a region. The empirical analysis suggests that the optimal radius for
      the 20 regions of Bangladesh varies from about 6 to 12 km. If the optimal radius
      of the catchment area is used in planning health centre locations, Bangladesh
      will need to set up 450 EOC facilities; currently there are only 90 such
      facilities.

PMID- 11527869
TI  - Research in action: the training approach of the Joint Health Systems Research
      Project for the Southern African Region.
AB  - Over the last two decades, capacity-building in health research has been
      recognized as a priority by the international research community. Since 1987 the
      Joint Health Systems Research (HSR) Project for the Southern African Region has
      been making efforts to increase the national expertise for operational health
      research, starting in ten Southern African countries, in order to strengthen
      decision-making in health care at all levels. Initially, its targets were health
      managers and public health staff. Step-by-step, staff of different levels and
      disciplines have, in small groups, developed and implemented research protocols
      on problems experienced in their own working environment. The recommendations
      resulting from over 200 studies could, to a large extent, be implemented by the
      teams themselves. The Project was characterized by a flexible approach, allowing
      countries to participate at their own speed and to determine their own activities
      and the support they needed. As Ministries of Health as well as research
      institutions, in an increasing number of Southern and Eastern African countries,
      choose to actively participate in HSR, this has contributed to bridge the gap
      between the academic world and the health field. Still, sustainability of HSR
      activities remains a challenge. This paper describes the approach of the Joint
      HSR Project over the first 10 years of its operation, and its major strengths and
      limitations.

PMID- 11527870
TI  - Is equity being sacrificed? Willingness and ability to pay for schistosomiasis
      control in China.
AB  - Decentralization of the health care system in China has led to an increasing need
      for income generation at all operational levels, both for curative services and
      for public health programmes. In general, people have accepted the costs of
      curative services, although the impact of charges on health-seeking behaviour has
      yet to be assessed. Public health programmes present particular problems in terms
      of revenue generation, however, because of the less direct impact of these
      activities on individual health and well-being. In this paper, we report the
      results of a cross-sectional study of willingness and ability to pay for
      schistosomiasis control. Questionnaires were administered to household heads of
      six representative villages in the Dongting Lake Region of Hunan Province, China.
      A total of 628 valid questionnaires were analyzed. The yearly mean household
      expenditure on schistosomiasis diagnosis and treatment was RMB 59.50 +/- 146.04
      Yuan (US$1 = 8 RMB Yuan), accounting for 0.94% of the total yearly household
      income. Most household heads (514, 82%) thought schistosomiasis was the greatest
      health threat in their communities, but only 30.9% of them were willing to pay
      for screening, diagnosis and treatment of the infection. On the other hand, 72.3%
      of the respondents were willing to undertake volunteer work for control.

PMID- 11527871
TI  - Changing access to health services in urban China: implications for equity.
AB  - The ongoing reform of public institutions and state-owned enterprises in urban
      China has had a profound impact on the financing, organization and provision of
      health services. Access to health care by the urban population has become more
      inequitable. One of the most pressing concerns is that those who have lost jobs
      have increasing difficulties accessing health care. Using the data from the
      national household health surveys conducted in 1993 and 1998, this paper presents
      empirical results of changing utilization of health care among different income
      groups. Over 16 000 households and 54 000 individuals in the urban areas were
      randomly selected to collect information on perceived need of and demand for
      health care and expenditures on the services. The findings show that the income
      gap between the highest and lowest income groups increased in real terms from
      1993 to 1998. There was a significant decline in the population covered by the
      government insurance scheme (GIS) and the labour insurance scheme (LIS), while
      the proportion of the population who had to pay for services out-of-pocket
      increased from 28% in 1993 to 44% in 1998. There was no statistically significant
      change in self-reported illness in the 2 weeks prior to survey among the study
      population over the period. While it was found that more people who reported
      illness from each income group received medical treatment of some kind, there was
      a decline in seeking care from a health provider. Among those in the lowest
      income group who reported illness but did not obtain treatment of any kind,
      nearly 70% (as compared with 38% in 1993) claimed financial difficulty as the
      major reason in 1998. The use of in-patient services dropped significantly from
      4.5% in 1993 to 3.0% in 1998. The decreased use of in-patient services was more
      serious in the lowest and lower income groups than in higher and highest income
      groups. The percentage of patients referred for hospital admission but not being
      hospitalized had a negative relationship with income level. We can conclude from
      the data analysis that access of the urban population, particularly the poor, to
      formal health services has worsened and become more inequitable since the early
      1990s. Among possible reasons for this trend are the rapid rise of per capita
      expenditure on health services and the decline in insurance coverage.

PMID- 11527872
TI  - The promise and limits of private medicine: health policy dilemmas in Nigeria.
AB  - Developments in health are easily among the best known human development
      indicators. Comparisons of life expectancy, infant mortality, access to safe
      water and similar data indicate the positions of individual countries. The
      political and economic processes which these indices reflect, or which inform the
      nature of health policy, are often not as clear or visible. These structural
      factors are either frequently ignored or mentioned only in passing, as
      illustrated in a recent paper published in this journal on the private medical
      enterprise in Nigeria (Ogunbekun et al. 1999). According to the authors, the
      generally low quality of public health services and high user fees have combined
      to make private medicine the 'unavoidable choice' of Nigerians. They identify
      benefits of private medicine as higher technical efficiency and contributing to
      fill the gap created by inadequate public sector services and to medical
      training. This paper argues that these claims are exaggerated, and that the
      authors seem to ignore Nigeria's political and economic processes, the health
      seeking behaviour of Nigerians, as well as the prevailing causes of morbidity and
      mortality. It is suggested that whereas the contributions of private medicine are
      significant, there are also several limitations, some of which originate from its
      for-profit raison d'etre. The ultimate aim of health development must include
      improved access to services and better health status for the majority of the
      people. Without any form of public supported programme of payments in Nigeria,
      these objectives are circumscribed, especially with high fees in the private
      system. It is concluded that while private medicine will continue to be available
      for those who can afford it, it is unlikely to provide solutions to Nigeria's
      morbidity and mortality problems, particularly in relation to epidemics such as
      the growing burden of HIV/AIDS.

PMID- 11527873
TI  - Newspaper reports as a source for injury data in developing countries.
AB  - Injuries are an important public health problem and a leading cause of death
      among adults and children. In most of the developing world, with rapid changes in
      lifestyle, rural development, urbanization, an increase in number of vehicles,
      introduction of mechanized farming and pesticides in agriculture, the effect of
      injuries on mortality and morbidity is expected to increase. Injuries have been
      infrequently studied in developing countries; their importance is incompletely
      understood and they are seriously neglected in health research and policy. The
      reasons for this situation may be many, but one important reason is the
      unavailability of data in countries to assess the magnitude of the problem.
      Hospital and police records are the primary data source for injuries in the
      majority of the developing world. Newspaper reports may be an alternative source
      for injury data. This hypothesis was tested in the Rawalpindi Division of
      Pakistan by collecting data from newspaper reports for both intentional and
      unintentional injuries for 6 months (January-June 1999). This was compared with
      police data for the same time period. The results revealed that newspapers report
      more injury-related events and for some categories, such as suicides, the
      reporting was far greater by newspapers than the police. We conclude that the
      current system of police data collection needs to be strengthened. Newspapers may
      serve as a comparative source of information to evaluate the coverage of police
      data.

PMID- 11527874
TI  - Calculating and presenting disability adjusted life years (DALYs) in cost
      effectiveness analysis.
AB  - Disability adjusted life years (DALYs) are the sum of the present value of future
      years of lifetime lost through premature mortality, and the present value of
      years of future lifetime adjusted for the average severity (frequency and
      intensity) of any mental or physical disability caused by a disease or injury.
      They have been used as an outcome indicator in micro economic evaluations as well
      as sectoral prioritization exercises using league tables of cost-effectiveness.
      However, many of the current analyses are not comparable or transferable because
      either the assumptions used differ or are unclear, and because results are not
      presented in a way that allows researchers or policy-makers to re-calculate and
      re-interpret findings for use in an alternative context. However, at times there
      have also been miscalculations. This may happen either because evaluators
      disagree with the assumptions behind DALYs or because the methods of calculation
      have not been set out clearly. This paper shows how to calculate DALYs for cost
      effectiveness analysis using a worked example. It also shows the impact of
      changing the age weighting and discount rates on estimates of cost-effectiveness,
      and suggests a set of minimum reporting criteria for using DALYs in cost
      effectiveness analysis. Finally, readers are introduced briefly to a selected
      literature arguing for and against the use of DALYs.

PMID- 11527875
TI  - Financing advances on salaries of health workers in Chad: an example of a
      feasible strategy to sustain the Bamako Initiative.

PMID- 11527876
TI  - Screening standards in assisted reproductive technologies. Is the British
      Andrology Society recommendation to recruit cytomegalovirus negative semen donors
      only, a reasonable one?
AB  - The British Andrology Society recently recommended the exclusion of all
      cytomegalovirus (CMV) seropositive semen donors to prevent the risk of congenital
      CMV infection. The recommendation is based on the results of recent studies that
      identified a high percentage of symptomatic congenital CMV infections in newborns
      of women with CMV seropositivity pre-existing to pregnancy and on the fact that
      CMV can be detected in semen of CMV seropositive men. These are not new data. CMV
      seropositive women can infect their fetuses with their own latent CMV strain that
      can reactivate, or with an exogenous strain that can be transmitted to them by a
      sexual partner, but also by contacts, for example with an excreting child. The
      efficiency of these various ways of transmission to the fetus and the factors
      that could influence this transmission are for the moment completely unknown. An
      infectious virus is recovered by culture in the semen of <5% of CMV seropositive
      men. Exclusion of a large population of donors on the sole criteria of a positive
      CMV serology introduces the general message that this part of the male population
      is also not suitable as possible partners in couples who have no fertility
      problems. The problem of congenital infection in neonates of CMV seropositive
      women is a complex one that has just begun to be investigated. No data exists
      concerning this risk in the setting of assisted reproduction. We think that
      alternatives to the drastic BAS recommendation exist and should be more deeply
      discussed.

PMID- 11527877
TI  - Sharing information with donor insemination offspring. A child-conception versus
      a family-building approach.
AB  - This paper suggests an innovative approach to the sharing of information between
      parents and their donor-conceived offspring. The 'family-building' approach is
      offered in the hope that it will stimulate discussion and development.
      Traditionally, the emphasis has been on telling the child about his/her donor
      conception. This has the potential to unintentionally separate the child from the
      parents. The family-building approach presents donor conception as an issue
      concerning all members of the family, thus encouraging the child to see
      him/herself as an integral part of this family's history. Within this approach,
      the semen provider is acknowledged for his contribution and for having an ongoing
      significance in the family. It is important, however, to clearly differentiate
      between him as the genitor and the child's father as the loving and nurturing
      male in the family. Implications for professionals include the need to
      acknowledge that donor insemination does not only enable a woman to become
      pregnant but that it creates a family with a past, present and future. Therefore
      it will be helpful to provide information about and explore attitudes towards
      this type of family-building before couples start treatment.

PMID- 11527878
TI  - Reactive oxygen species stimulate prostaglandin F2 alpha production in human
      endometrial stromal cells in vitro.
AB  - BACKGROUND: The present study was undertaken to investigate the effect of
      reactive oxygen species on prostaglandin F2 alpha (PGF2 alpha) production by
      human endometrial stromal cells (ESC). METHODS AND RESULTS: Isolated ESC were
      incubated with hydrogen peroxide, which induces lipid peroxidation. Hydrogen
      peroxide increased both intracellular and medium concentrations of PGF2 alpha (P
      < 0.01). A time course study showed that hydrogen peroxide significantly
      increased PGF2 alpha concentrations in the medium after 6 h incubation (P <
      0.01), after which no further increase was observed. To study whether the
      increase in PGF2 alpha production caused by hydrogen peroxide was mediated by
      cyclooxygenase, ESC were incubated with indomethacin (0.5 microg/ml), an
      inhibitor of cyclooxygenase, in the presence of hydrogen peroxide. Indomethacin
      significantly blocked the increases in PGF2 alpha production caused by hydrogen
      peroxide (P < 0.01). Hydrogen peroxide also increased PGF2 alpha production by
      decidualized ESC (P < 0.01), induced by the incubation with medroxyprogesterone
      acetate (10(-6) mol/l) and oestradiol (10(-8) mol/l). CONCLUSIONS: Reactive
      oxygen species stimulate PGF2 alpha production in ESC, suggesting that they might
      influence endometrial function by regulating PGF2 alpha production.

PMID- 11527879
TI  - Apoptosis in endometrial glandular and stromal cells in women with and without
      endometriosis.
AB  - BACKGROUND: The aetiology of endometriosis is unknown. Ectopic dissemination of
      the endometrial cells gives origin to endometriotic lesions, but occurs in women
      with and without endometriosis. It has been suggested that increased ectopic cell
      survival facilitates their implantation. The objectives of this study were to
      evaluate endometrial apoptosis in women with endometriosis according to: (i)
      cyclic changes, (ii) glandular and stromal contribution, and (iii) stage of the
      disease. METHODS: The subjects were women undergoing diagnostic laparoscopy and
      endometrial biopsies for suspected endometriosis. Spontaneous apoptosis was
      evaluated using TdT-mediated dUTP-biotin nick end-labelling (TUNEL) assay.
      Apoptotic cells per 10 mm(2) (apoptotic index) in an area of 10-50 mm(2) in 5
      microm endometrial tissue sections were counted and location of these cells was
      recorded. RESULTS: The apoptotic index in glandular epithelium was lower in
      endometriosis than controls (26.0 +/- 5.5 versus 51.2 +/- 9.7, P = 0.03) but not
      in the stroma (36.3 +/- 6.4 versus 48.4 +/- 11.3, NS). In controls, apoptosis was
      highest during the late secretory/menstrual and early proliferative phases and
      cyclic variability was apparent. In endometriosis, this cyclic variability was
      lost. There was a trend toward decreased apoptosis with increasing stage of the
      disease, but the differences lacked statistical significance. CONCLUSIONS:
      Spontaneous apoptosis is decreased in the endometrial glands in women with
      endometriosis, especially during late secretory/menstrual and early proliferative
      phases of the cycle. This may indicate increased viability of endometrial cells
      shed during menses, facilitating their ectopic survival and implantation.

PMID- 11527880
TI  - Origins of vaginal acidity: high D/L lactate ratio is consistent with bacteria
      being the primary source.
AB  - BACKGROUND: The origin of the lactic acid that acidifies the vagina is not well
      established. It is widely accepted that during times of high oestrogen (during
      the neonatal period and again during a woman's reproductive years) large amounts
      of glycogen are deposited in the vaginal epithelium and that the glycogen is
      anaerobically metabolized to lactic acid. What is not established is whether
      lactic acid is primarily produced by vaginal bacteria or by vaginal epithelial
      cells. Human cells can make only L-lactate, while bacteria can produce both D-
      and L-, thus the D- to L-lactate ratio can indicate the relative contribution of
      bacterially derived lactic acid. METHODS: In this study, we used chiral HPLC to
      examine the percentages of D- and L-lactate in vaginal secretions, in primary
      cultures of bacteria from these vaginal secretions, and in cultures of
      lactobacillus isolates of vaginal origin. RESULTS: We found that in most vaginal
      secretion samples, >50% of the lactic acid was the D-isoform (mean 55%, range 6
      75%, n = 14). CONCLUSIONS: Our results thus support the hypothesis that vaginal
      bacteria, not epithelial cells, are the primary source of lactic acid in the
      vagina.

PMID- 11527881
TI  - Relationship of ovarian stimulation response with vascular endothelial growth
      factor and degree of granulosa cell apoptosis.
AB  - BACKGROUND: The aim of this study was to evaluate the concentration of vascular
      endothelial growth factor (VEGF) in follicular fluid and in granulosa cell
      cultures in relation to the degree of apoptosis in granulosa cells from patients
      with different types of ovarian response to controlled ovarian hyperstimulation.
      METHODS: We studied 30 women who underwent controlled ovarian hyperstimulation
      and oocyte retrieval. Group A comprised patients with 1-4 follicles (n = 10),
      group B patients with 5-14 follicles (n = 10) and group C patients with >15
      follicles (n = 10). RESULTS: Mean (+/-SD) VEGF concentrations in follicular fluid
      were 1232 +/- 209, 813 +/- 198 and 396 +/- 103 pg/ml for groups A, B and C
      respectively (P > 0.01). Concentrations of VEGF in granulosa cell supernatant
      were 684 +/- 316, 1101 +/- 295 and 1596 +/- 227 pg/ml respectively (P < 0.05).
      Percentages of apoptotic cells in granulosa cells culture was 55.02 +/- 7.5,
      23.98 +/- 4.4 and 14.2 +/- 2.3% respectively (A versus B, P < 0.01, A versus C, P
      < 0.006, B versus C, NS). CONCLUSIONS: Our findings showed that in patients with
      decreased ovarian response to controlled ovarian hyperstimulation, follicular
      fluid VEGF concentration is elevated, the concentration from granulosa cells
      culture supernatant is decreased and the percentage of apoptotic granulosa cells
      is increased, while opposite findings occurred in patients with normal or hyper
      responses.

PMID- 11527882
TI  - Baseline non-fasting serum leptin concentration to body mass index ratio is
      predictive of IVF outcomes.
AB  - BACKGROUND: The present study was designed to determine whether circulating
      leptin concentrations and/or body mass index (BMI) in women undergoing IVF are
      predictive of outcomes. METHODS: IVF cycle outcomes, e.g. fertilization, embryo
      development, implantation, pregnancy, were analysed relative to baseline (i.e.
      day gonadotrophin stimulation was initiated) non-fasting serum leptin
      concentrations and BMI. RESULTS: Serum leptin concentrations correlated with BMI
      (r = 0.739, P < 0.0001) as expected. Multiple logistic regression analyses showed
      correlation between serum leptin and pregnancy success (likelihood ratio = 5.198,
      P < 0.05), but there was no association between pregnancy and BMI. However, the
      serum leptin to BMI ratio was more strongly correlated (likelihood ratio = 7.258,
      P < 0.01) with pregnancy success than was leptin alone. Moreover, women with a
      low leptin:BMI ratio (< or =0.3) had significantly more superior quality embryos
      on day 3 post-retrieval (2.5 versus 1.4, P < 0.05, Kruskal-Wallis) and a greater
      implantation rate (26.7 versus 13.2%, P < 0.025, chi(2)) than women with a high
      leptin:BMI ratio (> or =0.7). CONCLUSIONS: The leptin:BMI ratio appears to be
      highly predictive of IVF success. Elevated leptin concentrations, particularly
      relative to BMI, may negatively impact fertility by assisted reproduction,
      possibly through direct ovarian actions resulting in impaired oocyte quality
      and/or early embryo development.

PMID- 11527883
TI  - Oestradiol plus progesterone treatment increases serum leptin concentrations in
      normal women.
AB  - BACKGROUND: Previous studies have alluded to a role for both oestradiol and
      progesterone in the secretion of leptin from fat cells in the human, although
      direct evidence has yet to be obtained. The study aim was to assess serum leptin
      concentrations in normally cycling women receiving exogenous oestradiol and
      progesterone. METHODS: Normally cycling women were investigated in an untreated
      spontaneous cycle (control, n = 10), a cycle treated with oestradiol (oestradiol
      cycle, n = 10) and a cycle treated with oestradiol plus progesterone
      (oestradiol+progesterone cycle, n = 6). Oestradiol was given to the women through
      skin patches on cycle days 2, 3 and 4, and progesterone intravaginally on cycle
      days 3, 4 and 5. Serum concentrations of leptin, oestradiol, progesterone, FSH
      and LH were measured in daily blood samples. RESULTS: During the treatment, serum
      oestradiol and progesterone concentrations increased significantly. In the
      oestradiol cycles, leptin concentrations were not affected by treatment and did
      not differ from those in controls. In the oestradiol+progesterone cycles, leptin
      concentrations (mean +/- SEM) increased in all women from cycle day 3 (8.6 +/-
      1.1 ng/ml) to days 5 (12.2 +/- 1.8 ng/ml, P < 0.01) and 6 (11.9 +/- 2.0, P <
      0.05), and were at these points significantly higher than in the control cycles
      (P < 0.05). The mean percentage increase from day 3 to the peak concentration on
      days 5 or 6 was 62.6 +/- 6.8%. Leptin concentrations returned to the pretreatment
      value on day 7, together with the concentrations of oestradiol and progesterone.
      In the oestradiol+progesterone cycles, leptin concentrations correlated
      significantly with oestradiol and progesterone concentrations, but not with FSH
      and LH concentrations. CONCLUSIONS: These results show, for the first time, that
      leptin secretion can be stimulated in women by the administration of oestradiol
      plus progesterone. This may explain the increased concentrations of leptin during
      the luteal phase of the normal menstrual cycle.

PMID- 11527884
TI  - Endocrinological and ultrasonographic variations after immature oocyte retrieval
      in a natural cycle.
AB  - BACKGROUND: In-vitro oocyte maturation is an appealing alternative in
      reproductive medicine but the results obtained are still poor. The aim of our
      prospective and observational investigation was to study the hormonal
      modifications that immature follicular aspiration might induce in a natural cycle
      as well as the implications that these alterations may have in the endometrium.
      METHODS: Eleven patients (13 cycles) were included in our in-vitro oocyte
      maturation programme. Ovaries were scanned with transvaginal probes every day and
      follicular aspiration was performed when a follicle of 9 mm was visualized. Blood
      was also drawn for hormonal analysis. Endometrial thickness was recorded every
      day after oocyte retrieval. Two endometrial biopsies were taken on days 6 and 8
      after oocyte retrieval. RESULTS: We observed a significant drop in serum
      oestradiol concentrations after immature oocyte retrieval previous to follicle
      dominance. Immediately after, rises in both FSH and LH were detected. Also, a new
      dominant follicle started to grow 3-4 days later. Steroid hormones secreted by
      this newly recruited follicle were significantly lower than in controls, inducing
      inadequate endometrial thickness. CONCLUSIONS: These studies show that exogenous
      hormonal administration might be necessary to achieve a correct endometrial
      growth when in-vitro oocyte maturation is employed in IVF.

PMID- 11527885
TI  - Hypothalamic-pituitary-ovarian dysfunction after prepubertal chemotherapy and
      cranial irradiation for acute leukaemia.
AB  - BACKGROUND: We assessed adult hypothalamic-pituitary-ovarian function following
      treatment with chemotherapy and cranial irradiation for childhood acute
      lymphoblastic leukaemia. METHODS: The patients (n = 12) had median age at
      diagnosis of 4.7 years, and at assessment of 20.8 years. They collected a daily
      urine sample over two to five consecutive menstrual cycles (total of 41 cycles)
      for analysis of LH and steroid excretion. Blood sampling and ovarian ultrasound
      examination was performed in the early follicular phase. Sixteen healthy women
      with regular menstrual cycles were recruited as controls. RESULTS: Urinary LH
      excretion was significantly lower in patients throughout the cycle, particularly
      during the LH surge (P < 0.0001). The length of the luteal phase was
      significantly shorter in patients than in normal controls (12.2 +/- 0.3 versus
      13.6 +/- 0.4 days, P = 0.01) with a high prevalence of short (< or =11 days)
      luteal phases (15/39 cycles). Luteal phase pregnanediol excretion was slightly
      but not significantly lower. Follicular and luteal phase excretion of oestrone
      was lower in patients than in controls (P = 0.01). Early follicular phase plasma
      oestradiol was also lower in the patient group (P = 0.032) although LH, FSH,
      inhibin A and B concentrations were similar. CONCLUSIONS: These data indicate
      that treatment for childhood leukaemia results in subtle ovulatory disorder in
      some patients, probably related to cranial irradiation. Follow-up of these women
      is required to detect any effect on reproductive potential.

PMID- 11527886
TI  - Spontaneous regression over time of the germinal epithelium in a Y chromosome
      microdeleted patient: Case report.
AB  - Azoospermia factor (AZF) region microdeletions, which account for about 10-15% of
      patients with oligoazoospermia, seem to lack a close genotype-testicular
      phenotype correlation. Although many genetic and non-genetic factors may
      contribute to this outcome, it was thought that a spontaneous regression of
      testicular germ cells might also play a relevant role. The opportunity for
      carrying out two different testicular biopsies one year apart in an AZFc
      microdeleted patient enabled corroboration of this possibility. Indeed, the first
      biopsy showed a spermatocyte maturation arrest with mean Johnsen scores of 4 and
      3.9 in the right and left testes respectively. One year later, the right
      testicular biopsy showed a picture of Sertoli cell-only syndrome in 90% of the
      tubules examined, and of spermatogonial maturation arrest in the remaining
      tubules, with a mean Johnsen score of 2.1. The almost complete absence of
      germinal cells was confirmed by four left testicular sperm aspirations (TESA),
      conducted at the same time as the biopsy during an intracytoplasmic sperm
      injection cycle, which showed the almost exclusive presence of Sertoli cells (85%
      of the whole cell population). No spermatozoa could be retrieved by TESA or
      testicular biopsy. To our knowledge, this is the first case of a spontaneous
      regression of the germinal cell epithelium over time in a patient with a Yq
      microdeletion without the apparent intervention of any cause known to affect the
      germinal epithelium.

PMID- 11527887
TI  - Medical management of early fetal demise using a combination of mifepristone and
      misoprostol.
AB  - BACKGROUND: This study aims to assess the efficacy of a combination of
      mifepristone and misoprostol in the management of missed miscarriage and
      anembryonic pregnancy. METHODS: Data of 220 consecutive women with miscarriage,
      undergoing medical evacuation of the uterus were collected prospectively at an
      early pregnancy assessment unit in a tertiary referral hospital. Each woman
      received a single oral dose of mifepristone 200 mg and 36-48 h later vaginal
      misoprostol 800 microg. Three hours following the first dose, two further doses
      of misoprostol, 400 microg each, were administered vaginally or orally at 3 h
      intervals. Women who failed to pass products of conception were offered repeat
      medical regime with misoprostol. Success was defined as complete uterine
      evacuation within 3 days, without the need for surgical evacuation. RESULTS: The
      overall success rate of medical management was 84.1%. Mifepristone alone induced
      natural expulsion of products of conception in 18.1% of women. The median dose of
      misoprostol required was 1600 microg and the median induction miscarriage
      interval after first prostaglandin administration was 8.04 h (range: 0.58-50.54
      h). Of the 142 women who were symptomatic at presentation the medical regime
      failed in 30 (21.1%), compared with five (6.4%) failures of the 78 who were
      asymptomatic (P = 0.007). Of the 35 women who had surgical evacuation, eight
      required an emergency curettage for bleeding. CONCLUSIONS: The combination of
      oral mifepristone 200 mg with vaginal or oral misoprostol is an alternative to
      surgical management of early fetal demise, although it is not as effective as
      surgery.

PMID- 11527888
TI  - RASA, a recombinant single-chain variable fragment (scFv) antibody directed
      against the human sperm surface: implications for novel contraceptives.
AB  - BACKGROUND: A recombinant single-chain variable fragment (scFv) antibody was
      engineered to a tissue-specific carbohydrate epitope located on human sperm
      agglutination antigen-1 (SAGA-1), a sperm glycoform of CD52. METHODS AND RESULTS:
      cDNAs encoding the variable regions of the S19 [IgG(1)kappa] monoclonal antibody
      (mAb) were identified, linked, and cloned into the pCANTAB 5E vector. The
      recombinant anti-sperm antibody (RASA) was expressed in E. coli HB2151 cells as a
      29 kDa monomer and, remarkably, also formed multimers of approximately 60 and 90
      kDa. RASA reacted with the endogenous SAGA-1 antigen by Western blot analysis,
      labelled the entire human sperm surface by indirect immunofluorescence, and
      aggregated human spermatozoa in a tangled (head-to-head, head-to-tail, tail-to
      tail) pattern of agglutination, as was also observed with the native S19 mAb.
      CONCLUSIONS: These results demonstrate that active recombinant antibodies can be
      produced to a tissue-specific carbohydrate epitope on the human sperm surface,
      thereby opening opportunities for novel contraceptive agents.

PMID- 11527889
TI  - Low-dose dexamethasone augments the ovarian response to exogenous gonadotrophins
      leading to a reduction in cycle cancellation rate in a standard IVF programme.
AB  - BACKGROUND: Cancellation of assisted conception cycles because of poor ovarian
      response to gonadotrophins is a significant problem in assisted reproduction.
      Various adjuvant treatments have been suggested to improve responsiveness. This
      study reports on the potential benefits of low dose dexamethasone. METHODS:
      Patients <40 years of age were invited to participate in a twin centre
      prospective double blind randomized placebo controlled study. A total of 290
      patients were recruited and computer randomized using sealed envelopes to receive
      either 1 mg dexamethasone (n = 145) or placebo tablets (n = 145) in addition to a
      standard long protocol gonadotrophin-releasing hormone analogue with
      gonadotrophin stimulation regime. RESULTS: A significantly lower cancellation
      rate for poor ovarian response was observed in the dexamethasone group compared
      with controls (2.8 versus 12.4% respectively, P < 0.002). Further comparisons
      between the dexamethasone group and controls were made of median fertilization
      rates (60 versus 61% respectively, NS), implantation rates (16.3 versus 11.6%
      respectively, NS) and pregnancy rate per cycle started (26.9 versus 17.2%, NS).
      The benefit was apparent in patients both with polycystic and normal ovaries.
      CONCLUSION: Low dose dexamethasone co-treatment reduces the incidence of poor
      ovarian response. It may increase clinical pregnancy rates and should be
      considered for inclusion in stimulation regimes to optimize ovarian response.

PMID- 11527890
TI  - Serological investigation of Mycoplasma genitalium in infertile women.
AB  - BACKGROUND: The role of Mycoplasma genitalium in the pathogenesis of pelvic
      inflammatory disease has not been characterized. METHODS: Sera from 308 infertile
      women were investigated for antibodies to M. genitalium by immunoblotting. Women
      with tubal factor infertility (TFI) made up 132 of the patients, 67 of the women
      had an infertile male partner and 109 were infertile for unknown reasons.
      RESULTS: Of the TFI patients 29 (22.0%) were seropositive to the major adhesin,
      MgPa, of M. genitalium versus 11 (6.3%) in the group of women with normal tubes.
      No cross-reactions between MgPa and P1 of the related Mycoplasma pneumoniae were
      found. Besides, MgPa positive sera were confirmed by immunoblotting using a
      cloned fragment of the C-terminal part of MgPa specific to M. genitalium.
      Chlamydia trachomatis is known to be able to cause infertility as a result of
      salpingitis. Therefore, the sera were tested against C. trachomatis using a
      commercial ELISA test. Seventy-five (56.8%) of the TFI patients were seropositive
      to C. trachomatis. Eight (27.6%) TFI patients seropositive to MgPa were negative
      to C. trachomatis. CONCLUSIONS: This study indicates that M. genitalium may be an
      independent risk factor in the development of an inflammatory process leading to
      scarring of the uterine tubes in women and thereby causing infertility.

PMID- 11527891
TI  - Rescue of IVF cycles by HMG in pituitary down-regulated normogonadotrophic young
      women characterized by a poor initial response to recombinant FSH.
AB  - BACKGROUND: The aim of this study was to investigate the effects of adding human
      menopausal gonadotrophin (HMG) during controlled ovarian stimulation in
      normoovulatory normogonadotrophic patients showing an initial suboptimal response
      to a standardized long protocol therapy with recombinant FSH (rFSH) (300 IU/day).
      METHODS: A total of 43 such patients were randomized in two groups. In Group A,
      150 IU rFSH was substituted by 150 IU HMG after day 8 of stimulation. The
      stimulation protocol of Group B involved a simple increase of the daily rFSH dose
      to 375 IU after day 8. A total of 40 BMI and age matched patients with an optimal
      ovarian response formed the control group (Group C). RESULTS: The mean Group A
      serum concentration of oestradiol on the day of HCG administration and average
      number of oocytes retrieved were significantly higher than Group B (P < 0.001)
      and equivalent to Group C. A total of 10 pregnancies (50%) in Group A, 8 (34.8%)
      in Group B and 19 (47.5%) in the control group were achieved. CONCLUSIONS: The
      data suggest that LH supplementation improves the ovarian outcome in patients
      characterized by an inadequate initial response to rFSH therapy in a long
      protocol.

PMID- 11527893
TI  - The acrosome index, radical buffer capacity and number of isolated progressively
      motile spermatozoa predict IVF results.
AB  - BACKGROUND: The accuracy by which a number of newly described semen variables can
      predict either total fertilization failure (TFF) or pregnancy outcome in IVF, has
      not previously been investigated. The study aim was, therefore, to determine
      prospectively the predictive value of these variables. METHODS: The semen
      variables investigated were the post-wash total progressively motile sperm cell
      count (TPMC(post-wash)), the acrosome index (AI), 'cytoplasmic residues' and
      normal sperm morphology, evaluated according to the strict criteria ('strict
      criteria'), as well as the fast and slow total radical trapping antioxidant
      potential ('fast TRAP' and 'slow TRAP' respectively). RESULTS: The study group (n
      = 87) showed a mean (+/- SD) number of 10.2 +/- SD retrieved oocytes, 12.6% TFF,
      a mean fertilization rate of 59.7% and a pregnancy rate of 19.5% (17/87). TFF was
      significantly predicted by TPMC(post-wash), 'strict criteria', AI and
      'cytoplasmic residues' (all P < 0.05). The outcome after embryo transfer was
      significantly predicted by AI and 'fast TRAP'. Semen samples with an AI <5% and a
      'fast TRAP' <1.14 mmol/l in particular did not result in any pregnancies after
      IVF-embryo transfer. CONCLUSIONS: Of all the measured and calculated semen
      variables, TPMC(post-wash) was the best predictor of TFF, whilst AI and 'fast
      TRAP' were the best predictors of pregnancy after IVF.

PMID- 11527892
TI  - The questionable use of albumin for the prevention of ovarian hyperstimulation
      syndrome in an IVF programme: a randomized placebo-controlled trial.
AB  - BACKGROUND: The role of intravenous (IV) albumin administration in the prevention
      of ovarian hyperstimulation syndrome (OHSS) and in the improvement of IVF
      conception outcomes was evaluated in a prospective, randomized, placebo
      controlled double blind study. METHODS: Ninety-eight women were enrolled in the
      study and were consecutively assigned to either a treatment group or a control
      group. Eleven patients were lost to follow-up after assignment. Of the remaining
      87 women, 46 received albumin on the day of oocyte retrieval, and 41 received
      0.9% sodium chloride solution as a placebo control. Outcome measures included
      OHSS incidence rates and pregnancy rates in the two trial groups. RESULTS: Four
      of the 46 patients in the study group developed severe OHSS and six developed
      moderate OHSS. In the control group, one of the 41 developed severe OHSS and five
      developed moderate OHSS. The difference in OHSS incidence rates between the two
      groups was not statistically significant [relative risk (RR) = 1.49, 95% CI =
      0.59-3.73]. Fourteen patients (30%) in the intervention group conceived, compared
      with 16 patients (39%) in the control group. The difference in conception rates
      between the two groups was not statistically significant (RR = 0.78, 95% CI =
      0.44-1.39). CONCLUSIONS: Albumin appears to have no positive effect on OHSS or
      conception rates, while its use carries the risk of undesirable side effects,
      including exacerbation of ascites in OHSS, nausea, vomiting, febrile reaction,
      allergic reaction, anaphylactic shock and risk of virus and prion transmission.
      We suggest that this form of treatment should not be included in the prevention
      of OHSS.

PMID- 11527894
TI  - Endometrial markers of uterine receptivity utilizing the donor oocyte model.
AB  - BACKGROUND: Ethical constraints limit the ability to study peri-implantation
      phase human endometrium. In this study, the donor oocyte model was used to study
      candidate endometrial markers of uterine receptivity. METHODS: Archived, paraffin
      embedded tissue obtained by endometrial biopsy during cycle days 21-23 of
      patients undergoing 'mock' hormonal treatment cycles were evaluated by standard
      histological criteria and immunohistochemical staining for alpha v beta 3
      integrin and glycodelin. All of these patients (n = 101) had undergone a donor
      oocyte embryo transfer cycle utilizing the exact same hormonal protocol. RESULTS:
      Histological evaluation revealed 62 (61.3%) in-phase, 34 (33.7%) dyssynchronous,
      2 (2.0%) immature and 3 (3.0%) advanced endometria. The clinical outcomes of
      patients with either in-phase or dyssynchronous endometria were similar. Very
      strong correlations were noted between endometrial glandular dating and either
      alpha v beta 3 integrin or glycodelin immunostaining intensity (P < 0.001 for
      both). Glycodelin and alpha v beta 3 integrin immunostaining intensities were
      also highly correlated with each other (P < 0.001). CONCLUSIONS: Throughout the
      time period corresponding to the putative window of maximal endometrial
      receptivity (cycle days 21-23) a dynamic process was observed in exogenous
      hormonal replacement cycles characterized by a rapid histological advancement of
      endometrial glandular elements as well as progressive alpha v beta 3 integrin and
      glycodelin expression.

PMID- 11527895
TI  - One versus two embryo transfer after IVF and ICSI: a randomized study.
AB  - BACKGROUND: The main reason for adverse treatment outcome in assisted
      reproduction is the high rate of multiple pregnancies. The only strategy to avoid
      dizygotic twins is to transfer one embryo at a time. METHODS: A total of 144
      women, who had had at least four good quality embryos available after
      IVF/intracytoplasmic sperm injection (ICSI) and who had no more than one previous
      failed treatment cycle, were randomized to have either one or two embryos
      transferred. The treatment outcomes including those after frozen embryo transfer
      were compared between these groups. RESULTS: The clinical pregnancy rate per
      transfer was 32.4% in the one embryo transfer group and 47.1% in the two embryo
      transfer group, the difference being not significant. Eleven twin deliveries (n =
      39) occurred in the two embryo transfer group and there was one pair of
      monozygotic twins in the one embryo transfer group. The cumulative pregnancy rate
      per patient after transfer of fresh and frozen embryos was 47.3% in the one
      embryo transfer group and 58.6% in the two embryo transfer group. CONCLUSIONS:
      Our results indicate that among women who have good quality embryos in their
      first IVF/ICSI, good treatment results can be achieved. They support the idea of
      changing embryo transfer policy towards one embryo transfer without any
      remarkable decrease in the success rate, while dizygotic twins can be avoided.

PMID- 11527896
TI  - Ultrasound-guided embryo transfer maximizes the IVF results on day 3 and day 4
      embryo transfer but has no impact on day 5.
AB  - BACKGROUND: The use of ultrasound-guided embryo transfer has been reported to
      affect success rates in some centres but not others. In a prospective study, we
      examined the influence of ultrasound guidance in embryo transfer performed on
      different days after oocyte retrieval. METHODS: Two different methods of embryo
      transfer were evaluated in 1069 consecutive transfers. The ultrasound-guided
      embryo transfer was used in 433 cases, whereas 636 embryo transfers were
      performed with the tactile assessment ('clinical feel') method. RESULTS:
      Ultrasound-guided embryo transfer yielded a higher overall pregnancy rate than
      the 'clinical feel' approach, 47 versus 36% (P < 0.001). This difference was
      statistically significant where embryos were transferred after 3 or 4 days of
      culture, 45.9 versus 37.1% (P = 0.001) and 42.3 versus 27% (P = 0.035)
      respectively but not significant (P = 0.112) on day 5 embryo transfer (56.3
      versus 45.7%). Likewise, the implantation rate was significantly different
      between the two groups on day 3 and 4 embryo transfer, 23.3 versus 15.8% (P <
      0.01) and 21.6 versus 15.7% (P < 0.05%) respectively but no statistical
      difference was noted on day 5 embryo transfer, 26.7 versus 23.6%. CONCLUSION:
      Ultrasound assistance in embryo transfer on day 3 and 4 significantly improved
      pregnancy rates in IVF but had no impact on day 5.

PMID- 11527897
TI  - Birth of a healthy girl after ICSI with ejaculated spermatozoa from a man with
      non-mosaic Klinefelter's syndrome.
AB  - Klinefelter's syndrome is a major contributor to male infertility. Recent reports
      of births after ICSI with especially testicular spermatozoa from infertile men
      with this syndrome are promising. The birth of a healthy girl after ICSI
      treatment with ejaculated spermatozoa from a man with non-mosaic Klinefelter's
      syndrome is reported. The non-mosaic karyotype was confirmed by chromosome
      analysis of both peripheral blood leukocytes and fibroblasts from a skin biopsy.
      In conclusion, in a very few cases, men with apparently non-mosaic Klinefelter's
      syndrome have ejaculated spermatozoa that can result in a birth of a healthy
      child following ICSI.

PMID- 11527898
TI  - Characterization of subsets of human spermatozoa at different stages of
      maturation: implications in the diagnosis and treatment of male infertility.
AB  - BACKGROUND: Reactive oxygen species (ROS)-induced damage of membrane
      phospholipids and DNA in human spermatozoa has been implicated in the
      pathogenesis of male infertility. In this study, variations in ROS production,
      DNA structure (as measured by the sperm chromatin structure assay) and lipid
      composition, were studied in human spermatozoa at different stages of maturation.
      METHODS: Sperm subsets were isolated by discontinuous density gradient
      centrifugation of semen samples obtained from healthy donors and from infertility
      patients. RESULTS: DNA damage and ROS production were highest in immature
      spermatozoa with cytoplasmic retention and abnormal head morphology, and lowest
      in mature spermatozoa. Docosahexaenoic acid and sterol content were highest in
      immature germ cells and immature spermatozoa, and lowest in mature spermatozoa.
      The relative proportion of ROS-producing immature spermatozoa in the sample was
      directly correlated with DNA damage in mature spermatozoa, and inversely
      correlated with the recovery of motile spermatozoa. There was no correlation
      between DNA damage and sperm morphology in mature spermatozoa. CONCLUSIONS: The
      high levels of ROS production and DNA damage observed in immature spermatozoa may
      be indicative of derangements in the regulation of spermiogenesis. DNA damage in
      mature spermatozoa may be the result of oxidative damage by ROS-producing
      immature spermatozoa during sperm migration from the seminiferous tubules to the
      epididymis.

PMID- 11527899
TI  - Differential production of reactive oxygen species by subsets of human
      spermatozoa at different stages of maturation.
AB  - BACKGROUND: Reactive oxygen species (ROS)-mediated damage to human spermatozoa
      has been implicated in the pathogenesis of male infertility. Although ROS
      production by human spermatozoa has been extensively studied, the cell-to-cell
      variation in ROS production by spermatozoa at different stages of maturation has
      never been investigated. METHODS: In this study, we determined ROS production by
      subsets of human spermatozoa at different stages of maturation isolated by
      density gradient centrifugation of ejaculated spermatozoa obtained from healthy
      donors and from patients attending a clinic for infertility screening. RESULTS:
      Four different fractions were obtained. ROS production was highest in immature
      spermatozoa with abnormal head morphology and cytoplasmic retention and lowest in
      mature spermatozoa and immature germ cells (P < 0.01). ROS production was highest
      in immature spermatozoa from males with abnormal semen parameters compared with
      donors (P < 0.0001) or patients with normal semen parameters (P = 0.015). ROS
      production by immature spermatozoa was inversely correlated with the recovery of
      motile, mature spermatozoa in the high density fraction 4 (P = 0.01).
      CONCLUSIONS: The results of this study indicate that there is significant cell-to
      cell variation in ROS production in subsets of spermatozoa at different stages of
      maturation and that oxidative damage of mature spermatozoa by ROS-producing
      immature spermatozoa during sperm migration from the seminiferous tubules to the
      epididymis may be an important cause of male infertility.

PMID- 11527901
TI  - Developmental potential of elongating and elongated spermatids obtained after in
      vitro maturation of isolated round spermatids.
AB  - BACKGROUND: Round spermatid injections are associated with disappointing clinical
      outcomes, and although these cells have been shown to mature into late spermatids
      in vitro, the developmental potential of such gametes remains to be demonstrated.
      METHODS: Round spermatids were isolated from 12 testicle samples of patients with
      obstructive azoospermia, hypoplasia, complete maturation arrest, and incomplete
      Sertoli cell-only syndrome. They were cultured for 7 days at 32 degrees C, 5%
      CO(2)in air, in microdrops of Vero cell-conditioned medium containing 10%
      synthetic serum substitute. RESULTS: From the 238 round spermatids cultured,
      25.2% attained the elongating and 5.5% the elongated spermatid stage (3-4 days
      per step). Relatively higher maturation rates were found in cases with
      obstructive azoospermia, but differences were significant only for elongated
      spermatids (9.3%). No differences were found in maturation rates between cases
      with non-obstructive azoospermia (4.3% of elongated spermatids). Experimental
      microinjections with elongating and elongated spermatids revealed a low
      fertilization rate (40.9%) but a normal blastocyst formation rate (60%).
      CONCLUSIONS: Late spermatids resulting from in-vitro culture of round spermatids
      in conditioned medium, either in controls in cases with a spermiogenetic block,
      appeared able to successfully fertilize the human oocyte and elicit normal embryo
      development.

PMID- 11527900
TI  - Phosphatidylinositol 3-kinase inhibition enhances human sperm motility.
AB  - BACKGROUND: The number of spermatozoa with forward motility after capacitation
      procedures represents the limiting factor for application of IVF versus
      intracytoplasmatic sperm injection (ICSI) procedure in cases of
      oligoasthenozoospermia. The possibility of increasing this number may thus be of
      help to the patient. A complex array of signalling pathways is involved in the
      regulation of sperm motility and recent data pointed out an important role for
      kinase/phosphatase-regulated phosphorylation of proteins. Here, we investigated
      the role of phosphatidylinositol 3-kinase (PI3K), a lipid and protein kinase
      involved in the regulation of several biological aspects of somatic cells, on
      human sperm motility by using the specific PI3K inhibitor LY294002. METHODS AND
      RESULTS: We demonstrated that in-vitro incubation of swim-up selected or
      unselected human spermatozoa with LY294002 determined an increase of percentage
      forward motility in all the treated samples. The effect was dose-dependent with
      an EC(50) of 1.09 +/- 0.54 micromol/l. LY294002 also increased sperm movement
      characteristics and hyperactivation as evaluated by computer-assisted motion
      analyser. The compound was also able to overcome the detrimental effect of
      hydrogen peroxide and lithium chloride on sperm motility. CONCLUSIONS: Our
      results suggest a negative role for PI3K in the development and maintenance of
      sperm motility and suggest a possible use of PI3K inhibitors to enhance motility
      in cases of asthenozoospermia.

PMID- 11527902
TI  - Significance of serum inhibin B concentration for evaluating improvement in
      spermatogenesis after varicocelectomy.
AB  - BACKGROUND: The study aim was to clarify the relationship of serum inhibin B
      concentrations to recovery of spermatogenic function after varicocelectomy, both
      as a predictor of improvement in the seminogram and as a means of monitoring
      hormonal function after surgery. METHODS: Fifty-two varicocele patients,
      including five with normal sperm concentrations, were studied. Changes in the
      seminogram, serum hormone concentrations and serum inhibin B were evaluated in
      the 47 oligozoospermic patients after surgery. Preoperative inhibin B
      concentrations correlated significantly with serum concentrations of FSH (r =
      0.598, P < 0.0001) and testosterone (r = 0.380, P < 0.02). Inhibin B
      concentrations also correlated significantly with sperm concentration (r = 0.351,
      P < 0.02) and total testicular volume (r = 0.578, P < 0.0001). No significant
      correlation was seen between inhibin B and the Johnsen score. Preoperative
      concentrations of inhibin B were higher in patients who increased their sperm
      concentration after surgery (responders) than in those without improved
      concentrations (non-responders). No significant difference was observed between
      pre- and postoperative inhibin B concentrations in responders or non-responders.
      However, 15 of 25 (60%) patients with increased inhibin B showed improvement of
      the seminogram, while only five of 22 (23%) patients with no change or a decrease
      in inhibin B had any improvement (P < 0.05). CONCLUSIONS: Preoperative serum
      inhibin B concentration could not reliably predict a response to varicocelectomy.
      However, a change in serum inhibin B concentration after varicocelectomy might be
      helpful to evaluate the improvement of testicular function after varicocelectomy.

PMID- 11527903
TI  - Sperm swim-up techniques and DNA fragmentation.
AB  - BACKGROUND: Swim-up techniques for sperm separation may have detrimental effects
      on sperm DNA. We wished to determine whether the normal swim-up method with
      centrifugation used in our laboratory, which involves a centrifugation step, was
      harmful to sperm compared with swim-up without centrifugation. METHODS: Semen
      samples were obtained from patients undergoing IVF or andrology assessment. An
      aliquot was removed for fixation and subsequent DNA fragmentation determination.
      The remaining sample was divided into two equal parts, which were subjected to
      swim-up either with (normal swim-up) or without (direct-swim-up) centrifugation.
      Semen analysis was performed both before and after swim-up. DNA fragmentation, in
      spermatozoa previously fixed in 4% paraformaldehyde, was assessed by the terminal
      transferase-mediated DNA end-labelling procedure (TUNEL). The percentage of
      spermatozoa with DNA damage after each swim-up technique was compared with that
      in the original semen sample. RESULTS: DNA damage was <5% in most samples. No
      significant change in DNA fragmentation was observed between the two swim-up
      procedures, although the 'normal' swim-up sample had significantly less DNA
      fragmentation than the pre-swim-up sample. CONCLUSIONS: We conclude that our
      normal swim-up technique caused no more DNA damage to spermatozoa from normal
      semen samples than a direct swim-up technique that involved no centrifugation
      step.

PMID- 11527904
TI  - Developmental ability of chromosomally abnormal human embryos to develop to the
      blastocyst stage.
AB  - BACKGROUND: A correlation between morphology, developmental competence and
      chromosome abnormalities is established. However, since absolute correlations are
      rare, embryo selection remains one of the most arduous tasks in assisted
      reproduction. This study was undertaken in order to determine which chromosomal
      abnormalities are compatible with development to the blastocyst stage. METHODS:
      Embryos diagnosed by preimplantation genetic diagnosis (PGD) as chromosomally
      abnormal or unsuitable for transfer were cultured to day 5 or 6. Morphology and
      development were observed daily. After extended culture, embryos were fixed and
      analysed by two rounds of FISH with the same probes used for PGD. RESULTS: Some
      types of numerical chromosome abnormalities do not preclude full differentiation
      in vitro. For instance, extensive mosaicism was detected in blastocysts and
      trisomic embryos reached the blastocyst stage with a frequency of 37%.
      Interestingly, only those monosomies compatible with first trimester development
      (monosomy X and 21) were detected at blastocyst stage. CONCLUSION: Even though
      there is a strong selection against chromosomally abnormal embryos, extended
      culture to day 5 or 6 cannot be used as a reliable tool to select against
      clinically relevant chromosome abnormalities such as trisomies.

PMID- 11527905
TI  - Laser zona pellucida thinning--an alternative approach to assisted hatching.
AB  - BACKGROUND: The purpose of this study was to assess the efficacy and hatching
      characteristics of in-vitro cultured human embryos subjected to laser zona
      pellucida thinning. METHOD: Zona thinning was performed on 110 embryos using a
      non-contact 1.48 microm diode laser and the hatch rate in vitro was compared with
      42 control embryos. Variation of zona thickness and degree of zona expansion was
      assessed. Scanning electron microscopy was performed on embryos entrapped during
      hatching to identify the site of hatching. RESULTS: The rate of hatching was
      significantly higher in laser thinned blastocysts compared with control embryos
      (68 versus 33% respectively, P < 0.01). Laser thinning increased the variation of
      zona thickness in embryos from 11.6-27.3%. Natural zona thinning occurred in 92%
      of laser thinned hatching blastocysts and 100% of control embryos. CONCLUSION:
      These results suggest that laser zona thinning is effective and may provide
      significant advantages over conventional assisted hatching techniques, which
      create holes.

PMID- 11527906
TI  - Cryoloop vitrification yields superior survival of Rhesus monkey blastocysts.
AB  - BACKGROUND: Vitrification using the cryoloop procedure was evaluated for
      preservation of non-human primate blastocysts by comparing survival results from
      two different cryoprotectant mixtures with prior results from controlled rate
      cooling. METHODS: Rhesus monkey blastocysts were produced by intracytoplasmic
      sperm injection of mature oocytes from cycling females stimulated with
      recombinant human hormones. Morphologically well-formed blastocysts were divided
      between Procedure A (2.8 mol/l dimethylsulphoxide and 3.6 mol/l ethylene glycol
      with 0.65 mol/l sucrose and 25 micromol/l Ficoll in TALP-HEPES with 20% fetal
      bovine serum (TH20)) and Procedure B (3.4 mol/l glycerol and 4.5 mol/l ethylene
      glycol in TH20). After >48 h in liquid nitrogen, the removal of cryoprotectants
      was accomplished in the presence of a 3-step series of decreasing sucrose
      concentrations in TH20. Surviving embryos were co-cultured on buffalo rat liver
      cells. RESULTS: Of 16 blastocysts vitrified via Procedure A, 38% survived with
      minimal lysis and only one hatched in culture; in contrast, of 33 blastocysts
      vitrified by Procedure B, 85% survived and 71% hatched. Of 22 blastocysts
      cryopreserved by conventional slow cooling, 36% survived and 6% hatched. Transfer
      into three recipients, each with two embryos vitrified with Procedure B, resulted
      in a successful twin-term pregnancy. CONCLUSION: Modified cryoloop vitrification
      with a final solution of 3.4 mol/l glycerol and 4.5 mol/l ethylene glycol is a
      promising procedure for preserving Rhesus monkey blastocysts that is simple,
      rapid, and inexpensive.

PMID- 11527907
TI  - The Graduated Embryo Score (GES) predicts blastocyst formation and pregnancy rate
      from cleavage-stage embryos.
AB  - BACKGROUND: Embryo morphology and cleavage rates alone do not consistently
      identify embryos with high implantation potential following IVF. Blastocyst
      transfer has been reported to improve success rates by identifying potentially
      superior quality embryos. Algorithms for predicting IVF outcomes based on the
      presence of early developmental milestones have been proposed. Here we introduce
      the Graduated Embryo Score (GES). METHODS: Nucleolar alignment along the
      pronuclear axis, regular cleavage and degree of fragmentation at the first cell
      division, and cell number and morphology on day 3 were weighted to create a
      possible GES of 100 for each of 1245 fertilized embryos derived from 109 patients
      aged <40 years. The GES was correlated with IVF outcome. RESULTS: Of 983 embryos
      for extended culture, 349 (36%) developed to blastocyst and 180 (18%) were good
      quality (grade I-II). When ranked by cell number and morphology alone, 34% of
      embryos with > or =7 cells and <20% fragmentation formed good quality
      blastocysts. Using GES, embryos scoring 90-100 had 64% blastocyst formation
      compared with 31% scoring 70-85 and with 11% scoring 30-65. Embryos scoring 70
      100 had 44% blastocyst development compared with 9% scoring 0-65. Fifty-six
      patients (51%) conceived on-going gestations from 294 transferred embryos. In
      patients with at least one transferred embryo scoring > or =70, the pregnancy
      rate was 59% compared with 34% if all embryos scored <70. The overall
      implantation rate was 28%. Among embryos scoring 70-100, an implantation rate of
      39% was seen, compared with 24% among embryos scoring 0-65. CONCLUSIONS:
      Predicting which cleaved embryos will form blastocysts could permit the high
      success rates associated with blastocyst transfer to be achieved from day 3
      embryo transfer.

PMID- 11527908
TI  - Effects of supplementation with free radical scavengers on the survival and
      fertilization rates of mouse cryopreserved oocytes.
AB  - BACKGROUND: This study was conducted to investigate the effects of
      supplementation with free radical scavengers on the survival and fertilization
      rates of freeze-thawed mouse oocytes. METHODS: Superovulated oocytes with cumulus
      cells were cryopreserved by slow freezing in propanediol combined with a rapid
      thawing protocol. The cryopreservation medium was supplemented with the
      antioxidant enzymes superoxide dismutase (SOD) and catalase, and with the nitric
      oxide (NO) scavenger, haemoglobin (Hb). RESULTS: The addition of 50 IU/ml SOD
      showed significantly higher survival and fertilization capabilities compared with
      control (P < 0.01). Oocyte survival was greatly increased by concomitant addition
      of SOD with 10 IU/ml catalase (P < 0.01). On the other hand, the NO donor (sodium
      nitroprusside) inhibited survival and fertilization rates (P < 0.05).
      Significantly decreased survival and fertilization rates were also observed
      following the addition of high concentrations (10(-3) to 10(-6) nmol/l) of the NO
      synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME). In contrast,
      significantly better oocyte survival and fertilization rates were detected with
      low concentrations (10(-7) nmol/l) of L-NAME. Oocyte survival potential was
      significantly increased by addition of Hb (1 microg/ml, P < 0.05). Moreover,
      oocyte survival and fertilization rates were significantly promoted by the
      concomitant addition of SOD with Hb (P < 0.01). CONCLUSIONS: These results
      suggest that supplementation of free radical scavengers, particularly
      combinations of SOD with NO scavengers in freezing and thawing media, improved
      the post-thaw survival and fertilization rates of cryopreserved mouse oocytes.

PMID- 11527909
TI  - Reduction of post-surgical adhesions with ferric hyaluronate gel: a European
      study.
AB  - BACKGROUND: The objective of this study was to assess the safety and efficacy of
      a 0.5% ferric hyaluronate gel, in reducing adhesions in patients undergoing
      peritoneal cavity surgery by laparotomy, with a planned 'second-look'
      laparoscopy. METHODS: The study was a randomized (by computer-generated
      schedule), third party blinded, placebo-controlled, parallel-group design
      conducted at five centres in Europe. Females aged 18-46 years received 300 ml
      ferric hyaluronate (n = 38) or lactated Ringer's (n = 39) as an intraperitoneal
      instillate at the completion of surgery. At second-look 6-12 weeks later, the
      presence of adhesions was evaluated at 24 abdominal sites. RESULTS: Patients
      treated with ferric hyaluronate had significantly fewer adhesions compared with
      controls. When adhesions formed, they were significantly less extensive and less
      severe in the treated group. The American Fertility Society score for adnexal
      adhesions was reduced by 69% in the treatment group compared with controls. The
      safety profile of ferric hyaluronate-treated patients was comparable with those
      treated with lactated Ringer's solution. CONCLUSIONS: In conclusion, ferric
      hyaluronate was safe and highly efficacious in reducing the number, severity and
      extent of adhesions throughout the abdomen following peritoneal cavity surgery.

PMID- 11527910
TI  - Value of magnetic resonance imaging in predicting efficacy of GnRH analogue
      treatment for uterine leiomyoma.
AB  - BACKGROUND: Estimating pharmacological efficacy is important when selecting
      conservative treatment of uterine leiomyoma. Hence, the ability of magnetic
      resonance (MR) imaging to predict gonadotrophin-releasing hormone (GnRH) analogue
      efficacy was investigated. METHODS: A total of 85 lesions was studied in 40
      patients who were clinically diagnosed as having uterine leiomyoma and treated
      with GnRH analogue for 24 weeks. To evaluate changes in lesion size, T2-weighted
      and gadopentetate-dimeglumine (Gd-DTPA)-enhanced, T1-weighted MR images were
      obtained within 2 weeks before, and immediately after termination of, GnRH
      analogue treatment. RESULTS: An average 46.3% size reduction was observed in 45
      lesions (52.9%); these were seen as low signal intensity on T2-weighted images
      and enhanced by Gd-DTPA. Also, an average 44.7% size reduction was observed in
      lesions enhanced by Gd-DTPA, irrespective of signal intensity findings on T2
      weighted images. The average size reduction of unenhanced lesions was only 17.8%,
      and significantly different from enhanced lesions (P < 0.001). The prediction of
      efficacy was difficult in those lesions not enhanced. CONCLUSIONS: It is
      considered that evaluation of MR signal intensities, and the presence or absence
      of Gd-DTPA enhancement, would predict treatment efficacy before GnRH analogue
      administration.

PMID- 11527911
TI  - Relative risk of conversion from normoglycaemia to impaired glucose tolerance or
      non-insulin dependent diabetes mellitus in polycystic ovarian syndrome.
AB  - BACKGROUND: Cross-sectional studies have shown a high frequency of impaired
      glucose tolerance (IGT) and non-insulin dependent diabetes mellitus (NIDDM) in
      women with polycystic ovarian syndrome (PCOS). However, little is known about the
      change in glucose tolerance that occurs over a period of several years in women
      with PCOS. METHODS: Sixty-seven women with PCOS received a 75 g glucose tolerance
      test and measurement of lipids at baseline and at follow-up after an average time
      of 6.2 years. All women followed prospectively had normal glucose tolerance (n =
      54) or IGT (n = 13) at the start of the study. RESULTS: Change in glycaemic
      control from baseline was frequent, with 5/54 (9%) of normoglycaemic women at
      baseline developing IGT and a further 4/54 (8%) moving directly from
      normoglycaemic to NIDDM. For women with IGT at baseline, 7/13 (54%) had NIDDM at
      follow-up. Body mass index (BMI) at baseline was an independent significant
      predictor of adverse change in glycaemic control. CONCLUSIONS: Women with PCOS,
      particularly those with a high BMI, should be reviewed regularly with respect to
      IGT or NIDDM, as the frequency of impaired glycaemic control is high, and that
      the rate of conversion from normal glucose tolerance to IGT or NIDDM, or from IGT
      to NIDDM is substantial.

PMID- 11527912
TI  - Nuchal translucency measurement and pregnancy outcome after assisted conception
      versus spontaneously conceived twins.
AB  - BACKGROUND: Nuchal translucency (NT) measurement for Down's syndrome screening or
      detecting various fetal anomalies is a reliable sonographic marker. This study
      evaluates the contribution of NT screening in spontaneously conceived and
      assisted conception twin pregnancies. METHODS AND RESULTS: Maternal age at
      measurement, chorionicity, ultrasound features, karyotype results and pregnancy
      outcome were recorded prospectively and compared in 83 assisted reproduction
      treatment and 91 spontaneously conceived twins. Pregnancy outcome was evaluated
      according to maternal age, method of conception, NT data and chorionicity. NT
      measurements (> or =95 centiles of the normal range) were considered screen
      positive and mid-pregnancy fetal karyotyping was advised. Complicated pregnancy
      outcome, which could be signalled by increased NT, was defined as either
      chromosomal abnormalities, severe structural defects or fetal demise. Based on NT
      measurements, 16 fetuses (4.6%) were found to be screen-positive. Five of them
      had chromosomal aneuploidy and selective termination was performed. The parents
      also opted for this procedure in another five fetuses because of major structural
      abnormality diagnosed during NT assessment. No other chromosomal or major fetal
      abnormality were found post-natally. Although no difference was found in NT,
      crown-rump length and maternal age between spontaneous and assisted reproduction
      technology twin pregnancies, the former group had a significantly higher rate of
      screen-positive results (7 versus 2%, P = 0.047), amniocentesis uptake (33 versus
      22%, P = 0.014), monochorionic twining (32 versus 4%, P = 0.001) and complicated
      pregnancy outcome (11 versus 5%, P = 0.02). CONCLUSION: The present study
      confirms that first trimester target scanning can improve outcome by early
      detection and management of cases with an anomalous co-twin. It also identifies
      some differences between spontaneously and artificially conceived twin
      pregnancies in relation to this area of testing.

PMID- 11527913
TI  - Intrauterine haematomas in a recurrent miscarriage population.
AB  - BACKGROUND: This study examines the effect of intrauterine haematomas (IUH)
      discovered during early pregnancy ultrasound scanning in patients with recurrent
      miscarriage. Previous studies of IUHs have reported conflicting findings, and
      none studied women with recurrent miscarriage. METHODS: A total of 341 women with
      a viable pregnancy was included. Women with an IUH (n = 41) were compared with
      those without (n = 300). RESULTS: An IUH was identified by ultrasound in 12%
      (41/341) women. There were no differences in the number of live births between
      the two groups (25/41, 61% in the IUH group compared with 169/300, 56% without an
      IUH) or the number of miscarriages (6/41, 15% with an IUH compared with 72/300,
      24% without an IUH). Anti-phospholipid antibodies were more common in the IUH
      group (21/31, 68% compared with 103/244, 42% P < 0.01). More women with
      haematomas experienced vaginal bleeding (16/31, 52% compared with 47/244, 19%, P
      < 0.01). These associations did not affect pregnancy outcome. Also, no increase
      in the rate of pregnancy complications was observed in the IUH group.
      CONCLUSIONS: The presence of an IUH in this potentially high risk patient group
      does not have a deleterious effect on pregnancy outcome.

PMID- 11527914
TI  - Leptin and leptin-binding activity in women with recurrent miscarriage:
      correlation with pregnancy outcome.
AB  - BACKGROUND: Previous studies in humans and mice have suggested the importance of
      leptin in fetal growth. Recurrent miscarriage may be a result of abnormal
      placental and/or fetal development and therefore abnormal leptin levels may be
      associated with this form of pregnancy loss. METHODS: Leptin and leptin-binding
      activity (LBA) were measured in blood obtained from women who had a history of
      recurrent miscarriage (n = 53) during weeks 5-6 and 7-8 of pregnancy, and the
      concentrations were correlated with subsequent pregnancy outcome. RESULTS:
      Concentrations of leptin ranged from 1.4-62.8 ng/ml, but there was a strong
      correlation (r = 0.825, P < 0.001) between leptin values at weeks 5-6 and 7-8 in
      the same woman. Women who subsequently miscarried had significantly lower plasma
      leptin concentrations on both weeks 5-6 (13.34 +/- 2.1 ng/ml) (P < 0.05) and 7-8
      (13.71 +/- 2.4 ng/ml) (P < 0.01) of pregnancy, than women who subsequently had a
      term birth (22.04 +/- 2.43 ng/ml week 5-6, 24.76 +/- 3.66 ng/ml week 7-8). LBA
      values ranged from 1-8.5% but there was no significant difference in LBA in blood
      obtained from women who subsequently miscarried or had a live birth. CONCLUSIONS:
      The significantly lower concentrations of leptin in women who subsequently
      miscarried suggest that leptin may play a role in preventing miscarriage.
      However, as there was a considerable overlap between the values of leptin in
      women who subsequently miscarried, and those that had a live birth, these
      measurements are of limited use in the prediction of pregnancy outcome in these
      women.

PMID- 11527915
TI  - The role of genetic factors in age at natural menopause.
AB  - BACKGROUND: Environmental factors explain only a small part of the age variance
      at which menopause commences. The variation in natural menopause is a trait
      predominantly determined by interaction of multiple genes, whose identity and
      causative genetic variation remains to be determined. Menopause is a
      retrospective marker for the reproductive capacity of preceding years, since
      subfertility and infertility precede menopause at distinct time-intervals. In the
      present study we have investigated the contribution of genetic factors to
      menopausal age. METHODS: Data were collected from a random population sample of
      singleton and twin sisters participating in a prospective breast cancer screening
      project, who had subsequently experienced natural menopause. Heritability of
      menopausal age was estimated with analysis of variance, Mx modelling and Gibbs
      sampling. RESULTS: All produced almost identical heritability estimates of 0.85
      0.87 for singleton sisters, suggesting a strong genetic contribution to
      menopausal age. Twin data were used to distinguish additive genetic from common
      environmental effects; a heritability of 0.71-0.72 was determined, which does not
      deviate significantly from the estimate for singleton sisters. CONCLUSIONS:
      According to our findings, a woman with a family history of early menopause risks
      early menopause and consequently early reproductive failure herself.

PMID- 11527916
TI  - An attempt to reconstruct children's donor concept: a comparison between
      children's and lesbian parents' attitudes towards donor anonymity.
AB  - BACKGROUND: This study investigated the donor concept of children who were born
      by means of donor insemination (DI), and their lesbian parents. METHODS: A total
      of 41 children aged between 7 and 17 years, and 45 parents, took part in the
      follow-up study. In-depth topic interviews were used to reconstruct how DI
      children and their mothers perceived the donor. Data were collected about the
      birth story, about children's conversations with their mothers concerning donor
      characteristics and about children's and parents' attitudes towards the status of
      the donor. RESULTS: 54% of these children preferred donor anonymity at this point
      in their life, whereas 46% wanted to know more about the donor. The majority of
      the latter group would have liked to know the donor's identity, with boys
      outnumbering girls. The remaining children of this group were content with non
      identifying information. Children wanted to know more about the donors whereas
      the majority of the mothers preferred the donor to remain anonymous. CONCLUSIONS:
      Our results suggest that among DI children in general and among members of the
      same family, unit opinions differ on the status of the donor. A flexible system
      offering different types of donors seems to be necessary in order to meet the
      needs of each family.

PMID- 11527917
TI  - Is the observed association between increasing paternal age and delayed
      conception an artefact?

PMID- 11527919
TI  - The effect of intercourse on pregnancy rates during assisted human reproduction.

PMID- 11527921
TI  - Women with small ovarian volume and microdose GnRH agonist protocol.

PMID- 11527922
TI  - Offspring sex ratios and the causes of placental pathology: the case of placental
      abruption.

PMID- 11527924
TI  - Association of HLA class I and class II antigen expression and mortality in uveal
      melanoma.
AB  - PURPOSE: Malignant transformation of cells is frequently associated with
      abnormalities in human leukocyte antigen (HLA) expression. These abnormalities
      may play a role in the clinical course of the disease, because HLA antigens
      mediate interactions of tumor cells with T cells and NK cells. Uveal melanoma is
      a highly malignant tumor of the eye and is characterized by a hematogenic spread
      to the liver. Little is known about the role of HLA expression in progression of
      this malignant disease. METHODS: In the present study HLA class I antigen,
      beta(2)-microglobulin (beta(2)-m), and HLA class II antigen expression was
      analyzed in primary uveal melanoma lesions by immunoperoxidase staining with
      monoclonal antibodies of 65 archival clinical samples. The results were
      correlated with the clinical course of the disease. RESULTS: HLA class I antigen
      expression and beta(2)-m expression were downregulated in 40 and 35 lesions,
      respectively. HLA class II antigens were expressed in 30 lesions. Patients with
      high HLA class I, including beta(2)-m, and HLA class II antigen expression in
      their primary melanoma lesions had a significantly decreased survival (P = 0.009,
      P < 0.001, and P = 0.006, respectively). CONCLUSIONS: The findings argue against
      a major role of cytotoxic T-lymphocyte (CTL)-mediated control of tumor growth in
      the clinical course of uveal melanoma and are compatible with a potential role of
      NK-cell-mediated control of hematogenic metastatic spread.

PMID- 11527925
TI  - Detection of natural peptide antibiotics in human nasolacrimal ducts.
AB  - PURPOSE: To determine the expression and production of antimicrobial peptides by
      mucosal cells of the lacrimal passage in healthy and pathologic states. METHODS:
      Detection of bactericidal-permeability-increasing protein (BPI), heparin-binding
      protein (CAP37), human cationic antimicrobial protein (LL-37), human alpha
      defensin 5 (HD5), human alpha-defensin 6 (HD6), human beta-defensin 1 (HBD-1),
      and human beta-defensin 2 (HBD-2) was performed by reverse transcription
      polymerase chain reaction (RT-PCR). Intracellular deposition of lysozyme,
      lactoferrin, secretory phospholipase A(2), human neutrophil defensins (HNP-1, -2,
      and -3), human beta-defensin 1 (HBD-1), and human beta-defensin 2 (HBD-2) was
      analyzed immunohistochemically. Samples were obtained from 15 patients by surgery
      and from 10 cadavers. RESULTS: RT-PCR revealed BPI, CAP37, and HBD-1 mRNA in
      samples of healthy nasolacrimal duct epithelium. Additionally, HBD-2 mRNA was
      detected in epithelial samples from patients with dacryocystitis. Messenger RNAs
      for LL-37 and alpha-defensin 5 and 6 were absent in all samples investigated.
      Immunohistochemistry revealed lysozyme, lactoferrin, secretory phospholipase
      A(2), and HNP-1, -2, and -3 to be present in all samples, whereas HBD-1 was
      present only in some of the healthy and inflamed samples. Immunoreactive HBD-2
      peptide was visible only in some of the inflamed samples. CONCLUSIONS: The data
      suggest that the human efferent tear ducts produce a broad spectrum of
      antimicrobial peptides. Under inflammatory conditions, changes in the expression
      pattern occurred, revealing induction of the human inducible defensin HBD-2 and
      in some cases downregulation of HBD-1 and CAP37. Antimicrobial peptides have a
      therapeutic potential in dacryocystitis, in that they have a broad spectrum of
      antimicrobial activity and accelerate epithelial healing. However, caution is
      appropriate, because defensins also promote fibrin formation and cell
      proliferation, which are key elements in scarring processes, such as
      dacryostenosis.

PMID- 11527926
TI  - Isolation and characterization of galectins in the mammalian retina.
AB  - PURPOSE: Previous studies have suggested that galectins may be involved in
      retinal adhesion and photoreceptor cell survival. To elucidate the underlying
      mechanisms, the authors isolated retinal galectins, determined their types and
      distributions, and investigated the validity of the hypothesis, using rat models.
      METHODS: An antibody was prepared against a bovine retinal lectin that was
      isolated by use of a lactose-agarose column. cDNA of the lectin was isolated by
      screening of a bovine retinal cDNA library, using the antibody, and then was
      sequenced. The cDNAs of rat retinal galectins were also isolated by means of
      polymerase chain reaction and used to produce an antibody against recombinant
      galectin-3. Using the described antibodies, the authors examined the
      distributions of galectins in bovine and rat retinas, morphologic changes of rat
      retinas induced by the antibodies, and distributional changes of galectins in
      constant-light-exposed rat retinas. RESULTS: The cDNAs of bovine galectin-1, rat
      galectin-1, and rat galectin-3 were isolated. Galectin-1 was found in various
      regions, including the retinal pigment epithelium, outer limiting membrane, and
      outer plexiform layer in bovine and rat retinas. Galectin-3 was increasingly
      detected in the cytoplasm of Muller cells after constant light exposure after an
      increase in its transcript. Retinal detachment and vacuolation of the outer
      plexiform layer were induced in rat eyes by intravitreous injection of the anti
      galectin-1 antibody. CONCLUSIONS: Galectin-1 may be involved in adhesion of the
      photoreceptor and outer plexiform layers by interacting with glycoconjugates with
      beta-galactoside residues in the interphotoreceptor matrix and synaptic cleft
      matrix. Galectin-3 may increase in Muller cells of a degenerative rat retina,
      probably through endogenous anti-apoptosis.

PMID- 11527927
TI  - Ocular pathology in mitochondrial superoxide dismutase (Sod2)-deficient mice.
AB  - PURPOSE: To characterize the pathologic features in retina, optic nerve, and
      extraocular muscle of mitochondrial superoxide dismutase (Sod2)-deficient mice, a
      model of increased mitochondrial production of reactive oxygen species. METHODS:
      Morphometric and ultrastructural study of eyes of 43 homozygous sod2(tm1Cje-/-)
      mice and wild-type control animals. For retinal morphometric analysis, 32
      manganese 5,10,15,20-tetrakis (4-benzoic acid) porphyrin (MnTBAP)-treated animals
      aged either 9 to 10 days or 20 to 21 days were studied. Ultrastructural
      examination was performed on tissue from the treated animals, and 11 additional
      untreated mutant and control animals. RESULTS: In treated Sod2-deficient animals,
      the photoreceptor layer was thinner centrally at 9 to 10 days than in control
      animals (mean 8.8 vs. 14.7 microm). By 20 to 21 days, all retinal layers apart
      from the outer nuclear layer and retinal pigment epithelium (RPE) were thinner
      centrally in mutant animals (total retinal thickness, 233.2 vs. 272.6 microm;
      combined nerve fiber layer, ganglion cell layer, and inner plexiform layer, 86.2
      vs. 103.4 microm; inner nuclear layer, 51.8 vs. 60.3 microm; photoreceptors, 26.7
      vs. 35.6 microm). Optic nerve cross-sectional area was less in 20- to 21-day-old
      treated Sod2-deficient animals than in control animals. Mitochondrial morphologic
      abnormalities (swelling, pale matrix, and disorganized cristae) were found
      predominantly in older mutant animals' (16 and 20 to 21 days) RPE and in
      extraocular muscle of a 16-day-old untreated mutant. CONCLUSIONS: In sod2(tm1Cje
      /-) mice, there is relative progressive retinal thinning, with particular
      involvement of the inner retinal layers and an early effect on the photoreceptor
      layer, as well as mitochondrial morphologic abnormalities, all consistent with
      mitochondrial disease.

PMID- 11527928
TI  - Structural and ultrastructural changes to the sclera in a mammalian model of high
      myopia.
AB  - PURPOSE: The development of high myopia is associated with scleral thinning and
      changes in the diameter of scleral collagen fibrils in humans. In the present
      study, the association between these scleral changes and the losses in scleral
      tissue that have previously been reported in animal models were investigated to
      determine the relationship between changes in collagen fibril architecture and
      thinning of the sclera in high myopia. METHODS: Myopia was induced in young tree
      shrews by monocular deprivation of pattern vision for short-term (12 days) or
      long-term (3-20 months) periods. Scleral tissue from normal animals over a wide
      age range (birth to 21 months) was also collected to provide data on the normal
      development of the sclera. Light and electron microscopy were used to measure
      scleral thickness and to determine the frequency distribution of collagen fibril
      diameters in the sclera. Tissue loss was monitored through measures of scleral
      dry weight. RESULTS: Significant scleral thinning and tissue loss, particularly
      at the posterior pole of the eye, were associated with ocular enlargement and
      myopia development after both short- and long-term treatments. However, collagen
      fibril diameter distribution was not significantly altered after short-term
      myopia treatment, whereas, from 3 months of monocular deprivation onward,
      significant reductions in the median collagen fibril diameter were noted,
      particularly at the posterior pole. CONCLUSIONS: The results of this study
      demonstrated that loss of scleral tissue and subsequent scleral thinning occurred
      rapidly during development of axial myopia. However, this initial tissue loss
      progressed in a way that did not result in significant alterations to the
      collagen fibril diameter distribution. In the longer term, there was an increased
      number of small diameter collagen fibrils in the sclera of highly myopic eyes,
      which is consistent with findings in humans and is likely to contribute to the
      weakened biomechanical properties of the sclera that have previously been
      reported.

PMID- 11527929
TI  - Patients with persistent pain after enucleation studied by MRI dynamic color
      mapping and histopathology.
AB  - PURPOSE: To study possible causes of persistent pain in patients who underwent
      enucleation of the globe and in whom all other noninvasively detectable causes of
      pain had been ruled out. METHODS: Twenty patients were studied, 10 with
      intractable pain (score >5 on a 0-to-9 self-reporting pain scale) persisting for
      more than 6 months after enucleation (for various reasons) and 10 without pain
      (score <4) at least 6 months after enucleation. Magnetic resonance imaging (MRI)
      with dynamic color mapping (MRI-DCM) was used to quantify the motion of the optic
      nerve in millimeters per degree of gaze, 2 to 3 mm behind the implant.
      Histopathologic study of biopsy specimens was used to verify imaging findings.
      RESULTS: The optic nerve was attached to the implant in almost all (19/20)
      patients. On average, the motion was significantly less in patients with
      persistent intractable pain (0.04 mm/deg) than in patients without pain (0.08
      mm/deg; normal orbit, 0.13 mm/deg). A biopsy specimen was available in 5 of 10
      patients with persistent pain, and in 4 of those 5, microscopic neuroma was found
      close to the optic nerve-implant junction. CONCLUSIONS: In the enucleated orbit,
      the optic nerve is usually attached to the implant and soft tissue motion is
      decreased. In patients who have persistent pain after enucleation, motion is
      decreased even more, and a high percentage of microscopic amputation neuromas are
      found. Increased stiffness of orbital soft tissue and optic nerve attachment
      after enucleation are detectable using MRI-DCM, and may play a role in
      susceptible patients in the development of microscopic amputation neuroma and
      pain.

PMID- 11527930
TI  - Somatostatin receptor gene expression in human ocular tissues: RT-PCR and
      immunohistochemical study.
AB  - PURPOSE: Somatostatin (SST) analogues have been used to treat proliferative
      diabetic retinopathy, pseudotumor cerebri, thyroid orbitopathy, and cystoid
      macular edema. There is a paucity of published data in regards to cell-specific
      distribution of SST receptors (SSTR) in normal human eye tissues. Gene expression
      for all five known SSTRs in normal human ciliary body/iris, retina, choroid, and
      cultured retinal pigment epithelial (RPE) cells were studied. METHODS: mRNA was
      isolated from human ocular tissues (iris/ciliary body, retina, and choroid)
      dissected from eight pairs of normal eyes (9-62 years) and from RPE cells grown
      in culture. RT-PCR was done for all five SSTRs in all analyzed tissues.
      Immunohistochemistry for SSTR1 and SSTR2 was performed on eight pairs of normal
      human eyes (28-74 years) imbedded in paraffin. RESULTS: SSTR1 to 5 genes are
      expressed in retina, SSTR1 and SSTR2 genes in cultured RPE cells, and SSTR1, 2,
      and 4 in ciliary body and choroid. SSTR1 and SSTR2 immunoreactivity (-ir) was
      observed on a variety of cells within all analyzed tissues including cornea,
      iris, trabecular meshwork, Schlemm's canal, ciliary processes, ciliary muscle,
      retina, choroid, cultured RPE cells, and optic nerve. CONCLUSIONS: SSTR genes are
      widely expressed in normal human eye tissues, with genes for SSTR1 and SSTR2
      being the most widely expressed. Genes for all SSTRs are expressed in retina.
      SSTR1-ir and SSTR2-ir were observed in all analyzed ocular tissues. Detailed
      knowledge of SSTRs distribution and function in the human eye will result in a
      better understanding of their role in health and disease.

PMID- 11527931
TI  - Structure, chromosomal location, and tissue-specific expression of the mouse
      opticin gene.
AB  - PURPOSE: To determine the structure, location, and tissue-specific expression of
      the mouse opticin gene (Optc) and to compare expression in the eye with that of
      Prelp, collagen II, and collagen IX. METHODS: Expressed sequence tags (ESTs) to
      mouse opticin were identified and the full-length sequence obtained after PCR
      reactions using a 15-day-postconception (dpc) whole-mouse embryo cDNA library.
      The mouse chromosomal localization of Optc was determined by radiation hybrid
      mapping and its genomic structure determined using an Optc-containing BAC clone.
      Tissue-specific expression of opticin, PRELP, collagen II, and collagen IX mRNAs
      was investigated by in situ hybridization and by dot blot hybridization for
      opticin. RESULTS: The Optc gene was localized to mouse chromosome 1 at 74.3 cM
      and consisted of seven exons spanning 10 kb. The Optc gene was less than 4 kb
      from the Prelp gene. In situ hybridization localized opticin mRNA exclusively to
      the presumptive ciliary body during development and to the nonpigmented ciliary
      epithelium of the adult mouse eye. Expression of Prelp was also detected in the
      nonpigmented ciliary epithelium of the adult eye. However, expression of collagen
      types II and IX was detected largely in the developing mouse eye, with type IX
      expression confined primarily to the presumptive ciliary body. CONCLUSIONS: The
      Optc, Prelp, and fibromodulin (Fmod) genes form a cluster on mouse chromosome 1.
      Opticin may represent a marker for ciliary body differentiation. Continued
      expression of opticin in the adult mouse eye suggests functions other than that
      of putative regulator of vitreous collagen fibrillogenesis.

PMID- 11527932
TI  - Novel cytochrome P4501B1 (CYP1B1) gene mutations in Japanese patients with
      primary congenital glaucoma.
AB  - PURPOSE: To investigate CYP1B1 gene mutations in Japanese patients with primary
      congenital glaucoma (PCG). METHODS: Sixty-five unrelated Japanese patients with
      PCG were screened by PCR-single-strand conformational polymorphism (SSCP)
      analysis followed by direct sequencing. No patients were offspring of
      consanguineous marriages, a common occurrence among patients in previous reports.
      PCG haplotypes were constructed with intragenic polymorphisms in affected
      individuals. Three-dimensional atomic structures of human CYP1B1 and four mutant
      CYP1B1 sequences representing missense mutations were assembled using homology
      modeling and were regularized by an energy-minimization procedure. RESULTS:
      Eleven novel mutations, including seven definite and four probable mutations,
      were detected in 13 (20%) of the 65 unrelated patients. Of the seven definite
      mutations, three were predicted to truncate the CYP1B1 open reading frame. The
      other four were missense mutations (Asp192Val, Ala330Phe, Val364Met, and
      Arg444Gln), all located in conserved core structures determining proper folding
      and heme-binding ability of cytochrome P450 molecules. Molecular modeling
      demonstrated that two of four mutations in positions 330 and 364 were
      structurally neutral, but Arg444Gln caused significant structural change. Of the
      four probable mutations, three were missense (Val198Ile, Val320Leu, and
      Glu499Gly); the other was a base substitution in the noncoding region of exon 1.
      CONCLUSIONS: The 11 varied CYP1B1 mutations found in 13 unrelated Japanese
      patients with sporadic occurrence of PCG represent an allelic heterogeneity and
      may be unique to a specific population.

PMID- 11527933
TI  - Clinical features and mutations in patients with dominant retinitis pigmentosa-1
      (RP1).
AB  - PURPOSE: To survey patients with dominant retinitis pigmentosa (RP) for mutations
      in the RP1 gene to determine the spectrum of dominant mutations in this gene, to
      estimate the proportion of dominant RP caused by this gene, and to determine
      whether the clinical features of patients with RP1 mutations differ from features
      of those with rhodopsin mutations. METHODS: A set of 241 patients who did not
      have mutations in the rhodopsin gene (based on previous work) formed the basis
      for the study. Of these patients, 117 had also been previously evaluated and were
      found not to carry mutations in the RDS gene. The single-strand conformation
      polymorphism (SSCP) method was used to search for sequence variants, which were
      then directly sequenced. The relatives of selected patients were recruited for
      segregation analyses. Clinical evaluations of patients included a measurement of
      Snellen visual acuity, final dark adaptation thresholds, visual fields, and ERGs.
      Clinical data were compared with those obtained earlier from a study of 128
      patients with dominant rhodopsin mutations. RESULTS: Of the 241 patients, all
      were screened for the most common RP1 mutation (Arg677Ter), and 10 patients were
      found to have this mutation. In addition, an evaluation of a subset of 189
      patients in whom the entire coding sequence was evaluated revealed the following
      mutations: Gln679Ter (1 case), Gly723Ter (2 cases), Glu729(1-bp del) (1 case),
      Leu762(5-bp del) (2 cases), and Asn763(4-bp del) (1 case). All of these mutations
      cosegregated with RP in the families of the index patients. Nine missense
      mutations that were each found in six or fewer patients were encountered. The
      segregation of eight of these was evaluated in the respective patients' families,
      and only one segregated with dominant RP. This cosegregating missense change was
      in cis with the nonsense mutation Gln679Ter. Although patients with RP1 mutations
      had, on average, slightly better visual acuity than patients with rhodopsin
      mutations, there was no statistically significant difference in final dark
      adaptation thresholds, visual field diameters, or cone electroretinogram (ERG)
      amplitudes. Comparably aged patients with RP1 mutations had visual function that
      varied by approximately two orders of magnitude, based on visual fields and ERG
      amplitudes. CONCLUSIONS: Dominant RP1 alleles typically have premature nonsense
      codons occurring in the last exon of the gene and would be expected to encode
      mutant proteins that are only approximately one third the size of the wild-type
      protein, suggesting that a dominant negative effect rather than
      haploinsufficiency is the mechanism leading to RP caused by RP1 mutations. On
      average, patients with RP1 mutations have slightly better visual acuity than
      patients with dominant rhodopsin mutations; otherwise, they have similarly severe
      disease. The wide range in severity among patients with RP1 mutations indicates
      that other genetic or environmental factors modulate the effect of the primary
      mutation.

PMID- 11527934
TI  - Locus for autosomal recessive nonsyndromic persistent hyperplastic primary
      vitreous.
AB  - PURPOSE: To map the disease locus in a six-generation, consanguineous Pakistani
      family affected by nonsyndromic autosomal recessive persistent hyperplastic
      primary vitreous (arPHPV). All affected individuals had peripheral anterior
      synechiae and corneal opacities with variable degrees of cataract and a
      retrolenticular white mass behind the lens. METHODS: Genomic DNA from family
      members was typed for alleles at more than 400 known polymorphic genetic markers,
      by polymerase chain reaction. Alleles were assigned to individuals, which allowed
      calculation of lod scores. RESULTS: A maximum two-point lod score of 4.07 was
      obtained with marker D10S1225 with no recombination. Two recombinations with
      marker D10S208 and D10S537 localized the disease within a region of approximately
      30 centimorgans (cM). However, homozygosity across the region refined the arPHPV
      locus to 13 cM. CONCLUSIONS: Linkage analysis shows localization of nonsyndromic
      arPHPV to chromosome10q11-q21.

PMID- 11527935
TI  - Mutations in ABCR (ABCA4) in patients with Stargardt macular degeneration or cone
      rod degeneration.
AB  - PURPOSE: To determine the spectrum of ABCR mutations associated with Stargardt
      macular degeneration and cone-rod degeneration (CRD). METHODS: One hundred
      eighteen unrelated patients with recessive Stargardt macular degeneration and
      eight with recessive CRD were screened for mutations in ABCR (ABCA4) by single
      strand conformation polymorphism analysis. Variants were characterized by direct
      genomic sequencing. Segregation analysis was performed on the families of 20
      patients in whom at least two or more likely pathogenic sequence changes were
      identified. RESULTS: The authors found 77 sequence changes likely to be
      pathogenic: 21 null mutations (15 novel), 55 missense changes (26 novel), and one
      deletion of a consensus glycosylation site (also novel). Fifty-two patients with
      Stargardt macular degeneration (44% of those screened) and five with CRD each had
      two of these sequence changes or were homozygous for one of them. Segregation
      analyses in the families of 19 of these patients were informative and revealed
      that the index cases and all available affected siblings were compound
      heterozygotes or homozygotes. The authors found one instance of an apparently de
      novo mutation, Ile824Thr, in a patient. Thirty-seven (31%) of the 118 patients
      with Stargardt disease and one with CRD had only one likely pathogenic sequence
      change. Twenty-nine patients with Stargardt disease (25%) and two with CRD had no
      identified sequence changes. CONCLUSIONS: This report of 42 novel mutations
      brings the growing number of identified likely pathogenic sequence changes in
      ABCR to approximately 250.

PMID- 11527936
TI  - Incidence and progression rates of age-related maculopathy: the Rotterdam Study.
AB  - PURPOSE: To describe the incidence rate of age-related macular degeneration (AMD)
      and the progression rates of early stages of age-related maculopathy (ARM), and
      to study the hierarchy of fundus features that determine progression. METHODS: A
      group of 4953 subjects aged 55 years and older living in Rotterdam, The
      Netherlands, was studied at baseline and at 2-year follow-up to determine the
      incidence of neovascular and atrophic AMD. A subgroup of 1244 subjects was
      studied for progression of early stages of ARM. Fundus transparencies were graded
      for features of ARM using the International Classification System. ARM was
      stratified in four exclusive stages, according to type of drusen and presence of
      pigmentary irregularities. RESULTS: The overall 2-year cumulative incidence of
      AMD was 0.2%, increasing to 1.8% in subjects of 85 years and older. Of those in
      the early stages, one fourth showed progression to a more severe stage. The most
      important predictors for progression were more than 10% of macular area covered
      by drusen (odds ratio [OR] 5.7, 95% confidence interval [CI] 2.9-11.3), presence
      of depigmentation (OR 4.0, 95% CI 2.5-6.4), and hyperpigmentation (OR 3.4, 95% CI
      2.1-5.4). CONCLUSIONS: The incidence of AMD appears to be lower in The
      Netherlands than in the United States. Progression of early ARM stages occurs in
      a distinct pattern at a stable rate, with a large area of drusen and presence of
      pigmentary changes as the most important predictors.

PMID- 11527937
TI  - Morphology and neurochemistry of canine corneal innervation.
AB  - PURPOSE: To determine the architectural pattern and neuropeptide content of
      canine corneal innervation. METHODS: Corneal nerve fibers in normal dog eyes were
      labeled immunohistochemically with antibodies against protein gene product (PGP)
      9.5, calcitonin gene-related peptide (CGRP), substance P (SP), vasoactive
      intestinal polypeptide (VIP), and tyrosine hydroxylase (TH). Relative innervation
      densities and distribution patterns for each fiber population were assessed
      qualitatively by serial line-drawing reconstructions and quantitatively by
      computer-assisted analyses. RESULTS: More than 99% of all corneal PGP-9.5
      immunoreactive (IR) nerves contained both CGRP and SP, approximately 30%
      contained TH, and none contained VIP. Distribution patterns of corneal PGP-9.5-,
      CGRP-, SP-, and TH-IR nerves were indistinguishable, except that TH-IR fibers
      were absent from the corneal epithelium. Morphologically, canine corneal
      innervation consisted of a rich anterior stromal plexus, divided on the basis of
      morphologic criteria into anterior and posterior levels, and a rich epithelial
      innervation, characterized by large numbers of horizontally oriented, basal
      epithelial "leash" formations. Leash axons in all quadrants of the corneal
      epithelium oriented preferentially toward a common locus in the perilimbal
      cornea. CONCLUSIONS: The results of this study demonstrate for the first time the
      detailed architectural features, distinctive basal epithelial leash orientations,
      and peptidergic content of canine corneal innervation. The normal innervation
      pattern described in this study will provide other investigators with essential
      baseline data for assessing corneal nerve alterations in canine patients with
      spontaneous chronic corneal epithelial defects (SCCED) and other ocular diseases
      or injuries.

PMID- 11527938
TI  - Spontaneous chronic corneal epithelial defects (SCCED) in dogs: clinical
      features, innervation, and effect of topical SP, with or without IGF-1.
AB  - PURPOSE: To delineate the clinical features and alterations in innervation and
      substance P (SP) content in spontaneous chronic corneal epithelial defects
      (SCCED) in dogs and to conduct a preliminary investigation evaluating the
      efficacy of topical SP, with or without insulin-like growth factor (IGF)-1, in
      the treatment of this disorder. METHODS: Complete ophthalmic examinations,
      including Cochet-Bonnet aesthesiometry, were performed in 45 canine patients that
      had spontaneous corneal epithelial defects of at least 3 weeks' duration and with
      no identifiable cause. Eighteen patients had superficial keratectomies performed,
      and the corneal nerves were labeled immunohistochemically with antibodies against
      protein gene product (PGP)-9.5, SP, vasoactive intestinal peptide (VIP), and
      tyrosine hydroxylase (TH). Relative fiber densities were assessed qualitatively
      and quantitatively. Corneal epithelial cell and tear SP contents were determined
      in affected and normal dogs by an enzyme immunoassay. A preliminary open-label
      treatment trial of topical SP, with and without IGF-1, was conducted in 21 dogs.
      RESULTS: The duration of the erosion before admittance into the study was a mean
      of 9.22 weeks (range, 3-52). The average patient was middle aged (mean, 9.25 +/-
      1.85 years [SD]); no sex predisposition of the disease was identified. Boxers,
      golden retrievers, and keeshonds were overrepresented when compared with the
      normal hospital population. Corneal sensation was normal. Marked alterations in
      corneal innervation were identified in affected dogs with abnormal increased SP
      and calcitonin gene-related peptide (CGRP)-immunoreactive nerve plexuses
      identified surrounding the periphery of the epithelial defect. The SP content of
      epithelial cells surrounding the defect increased, whereas the tear SP content
      remained unchanged. Of the canine patients treated with SP, with or without IGF
      1, 70% to 75% had complete healing of the defect. CONCLUSIONS: This idiopathic
      spontaneous corneal disease in dogs shares clinical features with chronic
      epithelial defects in humans. The presence of marked alterations in peptidergic
      innervation and positive response to topical therapy with SP suggest that SP
      plays a critical role in corneal wound-healing processes.

PMID- 11527939
TI  - Morphology and immunohistochemistry of spontaneous chronic corneal epithelial
      defects (SCCED) in dogs.
AB  - PURPOSE: To determine the morphologic features of the epithelium and
      extracellular matrix in spontaneous chronic corneal epithelial defects (SCCED) in
      dogs. METHODS: Forty-eight superficial keratectomy specimens were obtained after
      confirmation of the presence of a superficial corneal erosion for longer than 3
      weeks with no discernible underlying cause. Histologic samples were examined by
      light microscopy, scanning electron microscopy, and transmission electron
      microscopy. Immunolocalization of laminin, collagen IV, fibronectin, and collagen
      VII was performed. RESULTS: Epithelial cells adjacent to the defect were poorly
      attached to the underlying extracellular matrix. A prominent superficial stromal
      hyaline acellular zone composed of collagen fibrils in the area of the erosion
      was present in most specimens. Samples exhibited a varying degree of fibroplasia,
      vascularization, and leukocytic infiltrate. Laminin, collagen IV, and collagen
      VII were usually either not present or were present only in discontinuous
      segments on the surface of the erosion. Fibronectin usually coated the surface of
      the erosion, either as a continuous sheet or in discontinuous segments.
      Transmission electron microscopy of 15 samples revealed that the basement
      membrane was either absent in the area of the erosion or was present only in
      discontinuous segments. Scanning electron microscopy of eight of nine samples
      confirmed the absence of continuous basement membrane. Epithelial and
      extracellular matrix components in the peripheral cornea appeared normal.
      CONCLUSIONS: Most canine patients with spontaneous chronic corneal epithelial
      defects do not have a normal basement membrane structure in the region of the
      epithelial defect and have other abnormalities in the subjacent extracellular
      matrix that may reflect a part of the underlying pathophysiology of chronic and
      recurrent erosions.

PMID- 11527940
TI  - Presence of nerves and their receptors in mouse and human conjunctival goblet
      cells.
AB  - PURPOSE: To determine whether neural pathways for controlling goblet cell
      secretion are present in mouse and human conjunctiva. METHODS: Mouse conjunctiva
      was homogenized and subjected to electrophoresis and Western blotting to detect
      PGP 9.5 (indicates nerves), muscarinic receptor subtypes (indicates
      parasympathetic pathway), and adrenergic receptors (indicates sympathetic
      pathway). Mouse eyes and human conjunctival tissue were analyzed by
      immunofluorescence microscopy. Antibodies to vasoactive intestinal peptide (VIP),
      tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DBH), and muscarinic and
      alpha(1)- and beta-adrenergic receptor subtypes were used. RESULTS: Western blot
      demonstrated PGP 9.5, M(1), M(2), and M(3) muscarinic receptors and alpha(1A)-,
      beta(1)-, beta(2)-, and beta(3)-adrenergic receptors in mouse conjunctiva.
      Immunoreactivity for VIP, TH, and DBH was found adjacent to mouse and human
      goblet cells. M(1) and M(2) muscarinic receptors were identified throughout mouse
      conjunctiva, but M(3) receptor was predominantly on goblet cells. All three
      muscarinic receptor subtypes were detected on goblet cells in human conjunctiva.
      alpha(1A)-Adrenergic receptors were found on epithelial cells and on goblet cells
      in mouse and human conjunctiva. beta(1)- and beta(2)-Adrenergic receptors were
      found on both epithelial and goblet cells in mouse conjunctiva, but not on human
      conjunctival cells. beta(3)-Adrenergic receptors were found on both epithelial
      and goblet cells in human conjunctiva but not on mouse conjunctival cells.
      CONCLUSIONS: The following conclusions were drawn: parasympathetic nerves and
      M(1), M(2), and M(3) muscarinic receptors, as well as sympathetic nerves are
      present on mouse and human goblet cells. The adrenergic receptors beta(1) and
      beta(2,) but not alpha(1A) and beta(3) are present on mouse conjunctival goblet
      cells, whereas alpha(1A) and beta(3,) but not beta(1) and beta(2) are present on
      human conjunctival goblet cells, suggesting that these nerves and receptors could
      activate goblet cell secretion in mouse and humans.

PMID- 11527941
TI  - Pro- and anti-inflammatory forms of interleukin-1 in the tear fluid and
      conjunctiva of patients with dry-eye disease.
AB  - PURPOSE: To compare the expression of the pro- and anti-inflammatory forms of
      interleukin (IL)-1 in the tear fluid and conjunctival epithelium of normal eyes
      and those with dry-eye disease. METHODS: The concentrations of IL-1 alpha, IL-1
      beta (precursor and mature forms), and IL-1 receptor antagonist (IL-1Ra) were
      measured by ELISA in tear fluid samples obtained from normal individuals and
      patients with dry eye who had rosacea-associated meibomian gland disease (MGD) or
      Sjogren's syndrome (SS) aqueous tear deficiency (ATD). These cytokines were also
      measured in normal tear fluid before and after nasal stimulation to induce reflex
      tearing. The relative expression of these cytokines was evaluated in conjunctival
      impression cytology specimens and conjunctival biopsy tissue obtained from normal
      subjects and SS ATD-affected patients using immunofluorescent staining. Matrix
      metalloproteinase (MMP)-9 concentration and activity in the tear fluid were
      evaluated with gelatin zymography and with an MMP-9 activity assay kit,
      respectively. RESULTS: Compared with normal subjects, the concentration of IL-1
      alpha and mature IL-1 beta in the tear fluid was increased, and the concentration
      of precursor IL-1 beta was decreased in patients with MGD (P < 0.05, P = 0.02,
      and P < 0.01, respectively) and SS ATD (P < 0.001, P = 0.02, and P < 0.001,
      respectively). There was no significant change in the concentration of IL-1
      alpha, precursor IL-1 beta, and IL-1Ra in reflex tear fluid, indicating that the
      lacrimal glands may secrete these cytokines. The activity of MMP-9, a
      physiological activator of IL-1 beta, was significantly elevated in the tear
      fluid of both dry-eye groups compared with normal subjects. A strong positive
      correlation was observed between the intensity of corneal fluorescein staining
      and the tear fluid IL-1 alpha concentration (r(2) = 0.17, P < 0.02) and the
      mature-to-precursor IL-1 beta ratio (r(2) = 0.46, P < 0.001). Positive
      immunofluorescent staining for IL-1 alpha, mature IL-1 beta, and IL-1Ra was
      observed in a significantly greater percentage of conjunctival cytology specimens
      from eyes with SS ATD than in those from normal eyes (P < 0.01 for IL-1 alpha, P
      < 0.009 for mature IL-1 beta, and P < 0.05 for IL-1Ra). CONCLUSIONS: Dry-eye
      disease is accompanied by an increase in the proinflammatory forms of IL-1 (IL-1
      alpha and mature IL-1 beta) and a decrease in the biologically inactive precursor
      IL-1 beta in tear fluid. Increased protease activity on the ocular surface may be
      one mechanism by which precursor IL-1 beta is cleaved to the mature, biologically
      active form. The conjunctival epithelium appears to be one source of the
      increased concentration of IL-1 in the tear fluid of patients with dry-eye
      disease. These results suggest that IL-1 may play a key role in the pathogenesis
      of keratoconjunctivitis sicca.

PMID- 11527942
TI  - Superoxide dismutase isoenzymes in the normal and diseased human cornea.
AB  - PURPOSE: The human cornea, a tissue much exposed to oxidative stress, is rich in
      extracellular superoxide dismutase (SOD). In this study, the contents and
      distributions of the SOD isoenzymes in the normal human cornea were compared with
      those in corneas affected by keratoconus and bullous keratopathy. METHODS: The
      central and peripheral parts of normal human corneas were analyzed separately.
      Central corneal buttons were obtained from patients with keratoconus and bullous
      keratopathy who were undergoing primary keratoplasty or retransplantation. SOD
      enzymatic activities were determined by a direct spectrophotometric method, and
      extracellular SOD and the cytosolic Cu- and Zn-containing SOD (CuZn-SOD) proteins
      were determined with ELISA and studied with immunohistochemistry. RESULTS: The
      total SOD content, and particularly the extracellular SOD content, was lower in
      the central than in the peripheral normal cornea. CuZn-SOD and extracellular SOD
      were demonstrated in all three corneal layers. CuZn-SOD was found in cells,
      whereas extracellular SOD appeared to be localized on cell surfaces, in basal
      membranes, and in the stroma. In keratoconus, corneal levels of extracellular SOD
      were half those in the control corneas, whereas CuZn-SOD and the mitochondrial Mn
      containing SOD levels were normal. In bullous keratopathy, apart from edematous
      dilution, SOD isoenzyme levels were essentially normal. In a remarkable finding,
      the same pattern in SOD isoenzyme levels as in the original disease was also
      found at retransplantation. CONCLUSIONS: Extracellular SOD and CuZn-SOD show
      markedly different distribution patterns within the human cornea. Extracellular
      SOD activity in the central cornea is halved in keratoconus, compared with that
      in normal control corneas. The finding of a similar reduction at
      retransplantation in keratoconus suggests reduced corneal extracellular SOD
      synthesis in cells of the host as a cause of the low enzyme levels.

PMID- 11527943
TI  - Modification of smooth pursuit initiation by a nonvisual, afferent feedback
      signal.
AB  - PURPOSE: To investigate the role of extraocular muscle afferent signals in the
      initiation and early maintenance of smooth-pursuit eye movements. METHODS: A
      suction scleral contact lens was used to impede the movements of the right eye
      while subjects tracked small targets in a step-ramp pursuit paradigm. Movements
      of the left eye were measured by infrared oculography. Pursuit latency, eye
      acceleration, and velocity were analyzed trial-by-trial and compared before,
      while, and after the right eye was impeded. RESULTS: When the right eye was
      impeded, initial acceleration and eye velocity were reduced. Pursuit latency was
      unchanged. The velocity effect had a rapid onset and offset; there was no
      evidence that the effects built up over a number of trials. Detailed analysis
      suggested that the reduction in velocity occurred approximately 40 msec after
      pursuit was initiated. CONCLUSIONS: These results are consistent with the
      hypothesis that extraocular muscle afferent signals provide a feedback signal of
      the movements of the eyes that may be used to modify the initiation and early
      maintenance of smooth pursuit on-line. It appears that for pursuit, as with
      saccades, the priority in these conditions is to maintain conjugacy.

PMID- 11527944
TI  - Increased elastin expression in astrocytes of the lamina cribrosa in response to
      elevated intraocular pressure.
AB  - PURPOSE: To determine whether abnormal elastin synthesis in the glaucomatous
      optic nerve head and lamina cribrosa is due to elevated intraocular pressure
      (IOP) or secondary to axonal injury, monkeys with elevated IOP and with optic
      nerve transection were compared. METHODS: Unilateral, chronic elevated IOP was
      induced in 11 rhesus monkeys by laser scarification of the trabecular meshwork.
      IOP was monitored weekly and maintained within 25 to 45 mm Hg for 7 to 36 weeks.
      In 6 monkeys, unilateral, optic nerve transection was performed, and monkeys were
      killed after 4 weeks. Optic nerve damage was assessed by stereoscopic slit-lamp
      biomicroscopy and fundus photography and by confocal scanning laser
      ophthalmoscopy. The eyes were enucleated and processed for immunohistochemistry
      and in situ hybridization and for electron microscopic immunogold detection of
      elastin. Axonal loss was evaluated in cross sections of the optic nerve stained
      with phenylenediamine. RESULTS: Compared with normal contralateral controls, the
      lamina cribrosa of eyes with elevated IOP exhibited markedly increased elastin
      and the presence of elastotic aggregates in the extracellular matrix and
      upregulation of elastin mRNA in the astrocytes. In transected eyes, elastin
      appeared as fine fibers in the lamina cribrosa, without elastotic aggregates, and
      without new synthesis or abnormal deposition of elastin. At the transected site,
      new synthesis of elastin was present in the pia mater but not in astrocytes in
      the glial scar. CONCLUSIONS: This study demonstrates that abnormal elastin
      synthesis in experimental glaucomatous optic neuropathy in the monkey is specific
      to elevated IOP and not secondary to axonal loss. The mechanisms by which
      elevated IOP induces enhanced elastin synthesis in laminar astrocytes are unknown
      but differ from those involved in acute axonal injury such as transection, where
      inflammation and breakdown of the blood-nerve barrier occur.

PMID- 11527945
TI  - Neurotrophin and neurotrophin receptor expression by cells of the human lamina
      cribrosa.
AB  - PURPOSE: To determine whether cells and tissue from the human lamina cribrosa
      (LC) express neurotrophin and tyrosine kinase (trk) receptor mRNA and protein and
      whether these cells secrete neurotrophins. METHODS: Synthesis of cDNA and the
      reverse transcription-polymerase chain reaction (RT-PCR) were conducted using
      total RNA obtained from well-characterized cell lines from the human LC and human
      optic nerve head (ONH) tissue. Immunofluorescent localization and Western blot
      analysis were used to evaluate neurotrophin and trk protein expression in cells
      and tissue from the human LC. Immunoassay systems (ELISAs) were used to detect
      the secretion of neurotrophins. RESULTS: Two morphologically distinct cell types
      (LC cells and ONH astrocytes) were isolated and characterized from the human LC.
      Messenger RNA for each of the neurotrophins, three full-length trk receptors and
      two truncated trk receptors were detected in both cell types and in human ONH
      tissue. Protein for the neurotrophins and trk receptors were detected in LC
      cells, ONH astrocytes, and ONH tissue. Neither cell type expressed mRNA or
      protein for the low-affinity neurotrophin receptor p75. The secretion of
      neurotrophins was observed in both cell types. CONCLUSIONS: Cells from the human
      LC express mRNA and protein of neurotrophins and trk receptors. In addition,
      cells from the LC secrete neurotrophins, which suggests that there is paracrine
      and/or autocrine signaling within the LC. Neurotrophin signaling within this
      region of the ONH may play important roles in the maintenance of the normal LC
      and in such diseases as glaucoma.

PMID- 11527946
TI  - Characterization of myocilin-myocilin interactions.
AB  - PURPOSE: To determine whether myocilin (MYOC; also referred to as TIGR) is
      present as a complex in human aqueous humor, whether part of the complex
      formation may be due to MYOC-MYOC interactions and to characterize the sites of
      interaction. METHODS: Human aqueous humor was analyzed by using a gel filtration
      column for the identification of MYOC complexes. MYOC-MYOC interactions were
      studied with a yeast two-hybrid system. Expression of full-length and truncated
      MYOC proteins in AH109 yeast was analyzed for growth and color on minimal medium.
      Site-directed mutagenesis was used to selectively mutate eight leucine residues
      within the leucine zipper motif. In vitro transcription and translation was used
      to verify yeast two-hybrid analysis. RESULTS: MYOC was found to be present in
      human aqueous humor as a complex ranging from 120 to 180 kDa. Expression of full
      length MYOC in yeast as well as in vitro binding studies revealed that MYOC can
      interact with itself. MYOC-MYOC interactions occurred mainly within amino acids
      117-166, a region containing a leucine zipper domain. Glycine substitution for
      selective leucine residues confirmed that MYOC-MYOC interactions occurred mainly
      within the leucine zipper domain. CONCLUSIONS: MYOC is present in human aqueous
      humor, not as a monomer but as a complex. Part of this complex may form due to
      MYOC-MYOC interactions that take place mainly within the leucine zipper domain.

PMID- 11527947
TI  - Long-term fluctuation in short-wavelength automated perimetry in glaucoma
      suspects and glaucoma patients.
AB  - PURPOSE: To determine the magnitude of the homogeneous, LF(Ho), and the
      heterogeneous, LF(He), components of the long-term fluctuation (LF) in glaucoma
      suspects and in stable primary open angle glaucoma (POAG) patients undergoing
      short-wavelength automated perimetry (SWAP) and to compare the magnitude of the
      SWAP LF components with those elicited by standard white-on-white (W-W)
      perimetry. METHODS: The sample comprised 33 glaucoma suspects and 17 patients
      with early-to-moderate stable POAG who underwent W-W perimetry and SWAP at each
      of six visits over a mean period of 12.75 months (SD, 2.29). The LF(Ho), LF(He),
      and error components of the long-term fluctuation were determined between the
      third and seventh visual field examinations. The intervening visual field
      examinations and the optic nerve head parameters, derived both by stereo
      observation and by the Heidelberg Retinal Tomograph, were used to confirm
      stability over the follow-up period. RESULTS: The LF(Ho) and LF(He) components
      were larger in the POAG patients than in the glaucoma suspects for both W-W
      perimetry and SWAP; the magnitude was independent of the depth of defect and of
      the short-term fluctuation. All three components of long-term fluctuation were
      greater for SWAP than for W-W perimetry, both in the glaucoma suspects and in the
      POAG patients. CONCLUSIONS: SWAP exhibits greater long-term fluctuation than
      white-on-white perimetry. The usefulness of SWAP will be limited if the extent of
      this variability is not overcome in future statistical procedures developed to
      detect progressive visual field loss.

PMID- 11527948
TI  - Cyclooxygenase-2 gene expression and regulation in human retinal pigment
      epithelial cells.
AB  - PURPOSE: Cyclooxygenases (COX) orchestrate a variety of homeostatic processes and
      participate in various pathophysiological conditions. The retinal pigment
      epithelium (RPE) cell performs a variety of regulatory functions within the
      retina. The conditions under which COX-1 and COX-2 are expressed and upregulated
      in human RPE (HRPE) cells were determined. METHODS: COX gene expression was
      examined using RT-PCR analysis of untreated HRPE cultures or cultures exposed to
      bacterial lipopolysaccharide or various cytokines. COX proteins were detected by
      immunohistochemistry and Western blot analysis. Prostaglandin (PG) production was
      analyzed by EIA. RESULTS: Examination of untreated RPE cells revealed the
      presence of COX-2 mRNA and the absence of COX-1 mRNA. Moreover, cytokine
      stimulation more readily enhanced COX-2 gene expression than COX-1 gene
      expression. IL-1 beta, the most potent inducer of COX-2, also resulted in
      detection of COX-2 protein by immunocytochemical staining and Western blot
      analysis. There was a direct relationship between both the appearance and amount
      of COX-2 mRNA and protein synthesis and the degree of PG synthesis by RPE cells.
      Furthermore, COX inhibitors significantly decreased PG production. Pretreatment
      of RPE cells with a NF-kappa B inhibitor, PDTC, resulted in dose-dependent
      decrease in IL-1 beta-induced COX-2 gene expression and PG production.
      CONCLUSIONS: COX-2 was the predominant isoform of cyclooxygenase in untreated
      HRPE cells. When HRPE cells were treated with proinflammatory cytokines, COX-2
      gene expression and synthesis of PGs were enhanced. NF-kappa B mediated the
      induction of COX-2 gene expression in HRPE cells. These studies indicate that RPE
      cells may participate in normal and pathologic retinal conditions through the
      induction of COX-2.

PMID- 11527949
TI  - Phospholipase A(2) in rabbit tears: a host defense against Staphylococcus aureus.
AB  - PURPOSE: This study analyzed rabbit tears for anti-staphylococcal activity, the
      role of phospholipase A(2) (PLA2) in this reaction, and the ability of enzyme
      inhibitors to promote bacterial survival. METHODS: Contact lenses with
      Staphylococcus aureus were applied to scarified rabbit eyes. The colony-forming
      units (CFU) per cornea or lens were determined and pathology was scored by slit
      lamp examination (SLE). The bactericidal activity was measured by incubating
      bacteria with rabbit tears or PLA2 at 33 degrees or 37 degrees C. Radiolabeled S.
      aureus was incubated with PLA2 or tears to quantify the release of a membrane
      component that was identified by thin-layer chromatography. Inhibitors of these
      reactions were also analyzed. RESULTS: Application of Staphylococcus, on contact
      lenses, to rabbit corneas resulted in bacterial killing and limited inflammation.
      Incubation of tears and bacteria (1:1; v/v) in tryptic soy broth at 33 degrees C
      decreased CFU approximately 4 logs. Tears (> or =30 microl) or PLA2 (> or =30 U)
      incubated with bacteria in phosphate-buffered saline were bactericidal. PLA2 (>
      or =0.2 U) or tears (> or =2 microl) cleaved bacterial membranes, liberating
      arachidonic acid. Spermidine or tetracaine inhibited cleavage of bacterial
      membranes by tears or PLA2 and spermidine promoted bacterial survival and growth
      in tears. Tears (60 microl) killed >99% of the bacterial inoculum, whereas
      bacteria incubated in tears plus spermidine approximately doubled in number.
      CONCLUSIONS: PLA2 in rabbit tears kills Staphylococcus by hydrolyzing bacterial
      membranes to release arachidonic acid. Spermidine and tetracaine inhibited PLA2
      activity and spermidine protected Staphylococcus from PLA2 in rabbit tears.

PMID- 11527950
TI  - Regional differences in functional receptor distribution and calcium mobilization
      in the intact human lens.
AB  - PURPOSE: To investigate regional differences in Ca(2+) mobilization kinetics in
      the intact human lens produced by exposure to agonists of tyrosine-kinase and G
      protein-coupled receptors and to characterize the major receptor subtypes
      involved in Ca(2+) signaling in the different regions. METHODS: Whole human
      lenses were placed anterior side down in a plastic chamber and perifused with
      artificial aqueous humor (AAH) at 30 degrees C. After fura-2 incorporation,
      cytosolic Ca(2+) levels were monitored by using epifluorescence techniques in
      either the equatorial or central anterior epithelial cells of the intact lens.
      Agonists dissolved in AAH were applied to the lens in successive short pulses.
      RESULTS: Central anterior lens epithelial cells produced a large response to 10
      microM acetylcholine (ACh) and histamine; only a small response to adenosine
      triphosphate (ATP); and no response to 10 microM adrenalin, 10 ng/ml epithelial
      growth factor (EGF) or TGF alpha, or 50 ng/ml platelet-derived growth factor
      (PDGF)-AB. Conversely, the equatorial cells produced a strong response to 10
      microM ATP and histamine, 10 ng/ml EGF (or TGF alpha), and 50 ng/ml PDGF-AB, but
      failed to respond to 10 microM ACh or 10 microM adrenalin. The EGF-induced
      response in the equatorial cells was blocked completely by tyrphostin (AG1478), a
      specific inhibitor of the EGF receptor tyrosine kinase. Carbachol, a
      nonhydrolyzable analogue of ACh, and pilocarpine, the M1 muscarinic receptor
      specific agonist, both produced the same trend of response amplitude elicited by
      ACh in each region of the lens. The potency order of purinergic agonist-induced
      Ca(2+) mobilization at the equator was consistent with the P2Y(2) receptor
      subtype. The histamine-induced response was abolished by 10 microM triprolidine,
      a specific H(1) receptor antagonist, but remained unaffected by the specific H(2)
      and H(3) antagonists, ranitidine and thioperamide, respectively. CONCLUSIONS.
      There is a spatial heterogeneity in functional receptor activity in different
      regions of the whole lens. The important growth factor receptors for EGF and PDGF
      are functionally active only in the equatorial cells of the mature human lens.
      This study further shows that the ACh, histamine, and ATP-induced responses arise
      from the activation of M1 muscarinic, H(1) histamine, and P2Y(2) purinergic
      receptors, respectively.

PMID- 11527951
TI  - Activation of a CFTR-mediated chloride current in a rabbit corneal epithelial
      cell line.
AB  - PURPOSE: To determine whether there is gene expression and functional activity of
      cystic fibrosis transmembrane conductance regulator protein (CFTR) in an SV40
      immortalized rabbit corneal epithelial cell line, tRCE. METHODS: Both whole-cell
      and cell-attached patch-clamp techniques were used to examine the biophysical
      characteristics of the cAMP-dependent chloride current. The molecular identity of
      this conductance was evaluated using RT-PCR analysis. RESULTS: In whole-cell
      patch-clamp studies, a cAMP-dependent chloride conductance was further
      facilitated by the known CFTR activator genistein (20 microM). Kinetic analysis
      of cell-attached patches containing few channels ascertained that genistein
      increased the chloride channel activity by increasing channel open probability
      (via an increased channel open time and a decreased channel closed time). In
      addition, in the presence of a reduced forskolin concentration (i.e., 100 nM),
      the chloride conductance generated could be augmented by the nonspecific
      phosphodiesterase enzyme inhibitor, IBMX (100 microM), implicating the importance
      of intracellular cAMP in the regulation of this conductance. Furthermore, this
      conductance exhibited voltage-dependent inhibition in the presence of the CFTR
      chloride channel blocker glibenclamide (250 microM), but was DIDS insensitive
      (500 microM). Consistent with the presence of a CFTR-mediated chloride
      conductance, the expression of CFTR-mRNA was detected using RT-PCR. Sequence
      analysis of the product revealed 99.4% homology to that described for rabbit
      CFTR. CONCLUSIONS: In tRCE cells, there is gene expression and functional CFTR
      activity. Its presence may have important therapeutic implications in corneal
      epithelial diseases resulting from declines in transepithelial secretory and
      fluid transport activity.

PMID- 11527952
TI  - Identification of Kir2.1 channel activity in cultured trabecular meshwork cells.
AB  - PURPOSE: To study the presence of inwardly rectifying K(+) (Kir) channels in
      cultured bovine (BTM) and human (HTM) trabecular meshwork cells. METHODS:
      Cultures of BTM and HTM cells were obtained by an extracellular matrix digestion
      technique. Whole-cell patch-clamp recordings of BTM cells were performed with the
      appropriate solutions to detect K(+) currents. Also, Western blot analysis of
      Kir2.1 protein expression was performed on both cultured BTM and HTM cells.
      RESULTS: A strong inwardly rectifying current at negative potentials to the
      equilibrium potential for K(+) (E(K+)) and highly selective for K(+) was detected
      in 60% of cultured BTM cells. The slope conductance of the inward rectification
      was more pronounced when the extracellular [K(+)] was increased and was
      proportional to [K(+)](0.45). The current was blocked by Ba(2+) and Cs(+) in a
      voltage- and concentration-dependent manner, with K(d) at 0 mV, of 74.7 microM
      and 45.6 mM, respectively. Current amplitude was reduced by increasing
      extracellular [Ca(2+)]. The current was insensitive to 10 microM glibenclamide
      and 10 nM tertiapin. The application of 100 microM 8-Br-cAMP reduced the current
      by 50%. Kir2.1 channel expression was detected in confluent monolayers of BTM and
      HTM cells by Western blot analysis. CONCLUSIONS: A population of cultured BTM
      cells expressed an inwardly rectifying K(+) current that illustrates the
      biophysical and pharmacologic characteristics of the detected Kir2.1 channel
      protein. Kir2.1 channels are also thought to be present in HTM cells. Kir2.1
      channels could be related to TM physiology, because they are involved in
      contractile and cell volume regulatory responses, two mechanisms that modify TM
      permeability.

PMID- 11527953
TI  - Inhibitory effect of ischemic preconditioning on leukocyte participation in
      retinal ischemia-reperfusion injury.
AB  - PURPOSE: Recent reports have shown that ischemic preconditioning induces strong
      protection against retinal damage by subsequent prolonged ischemia and that this
      protection is mediated by mechanisms involving the adenosine A1 receptor. This
      study was designed to evaluate quantitatively the effects of ischemic
      preconditioning on leukocyte-mediated reperfusion injury after transient retinal
      ischemia and to define the role of the adenosine A1 receptor in these effects.
      METHODS: Transient retinal ischemia was induced in male rats by temporary
      ligation of the optic nerve. Ischemic preconditioning (5 minutes of ischemia) was
      induced 24 hours before 60 minutes of ischemia. The adenosine A1 receptor
      antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) was administered
      intramuscularly immediately after ischemic preconditioning. Leukocyte behavior in
      the retina after 60 minutes of ischemia was evaluated in vivo with acridine
      orange digital fluorography. RESULTS: Ischemic preconditioning inhibited
      leukocyte rolling. The maximum number of rolling leukocytes was reduced to 3.0%
      at 12 hours after reperfusion (P < 0.01). Subsequent leukocyte accumulation was
      also decreased with ischemic preconditioning. The maximum number of accumulated
      leukocytes was reduced to 22.6% at 24 hours after reperfusion (P < 0.01). These
      inhibitory effects were suppressed by administration of DPCPX (P < 0.0001). The
      numbers of rolling leukocytes at 12 hours after reperfusion and accumulated
      leukocytes at 24 hours after reperfusion were 102.7% (NS) and 83.4% (P < 0.01),
      respectively, compared with the number without ischemic preconditioning.
      CONCLUSIONS: The present study demonstrates the inhibitory effects of ischemic
      preconditioning on leukocyte rolling and subsequent leukocyte accumulation during
      retinal ischemia-reperfusion injury. Furthermore, the adenosine A1 receptor may
      play an important role in these inhibitory effects.

PMID- 11527954
TI  - Three-dimensional topographic angiography in chorioretinal vascular disease.
AB  - PURPOSE: To evaluate a new angiographic technique that offers three-dimensional
      imaging of chorioretinal vascular diseases. METHODS: Fluorescein (FA) and
      indocyanine green angiography (ICGA) were performed using a confocal scanning
      laser ophthalmoscope. Tomographic series with 32 images per set were taken over a
      depth of 4 mm at an image frequency of 20 Hz. An axial analysis was performed for
      each x/y position to determine the fluorescence distribution along the z-axis.
      The location of the onset of fluorescence at a defined threshold intensity was
      identified and a depth profile was generated. The overall results of fluorescence
      topography were displayed in a gray scale-coded image and three-dimensional
      relief. RESULTS: Topographic angiography delineated the choriocapillary surface
      covering the posterior pole with exposed larger retinal vessels. Superficial
      masking of fluorescence by hemorrhage or absorbing fluid did not preclude
      detection of underlying diseases. Choroidal neovascularization (CNV) appeared as
      a vascular formation with distinct configuration and prominence. Chorioretinal
      infiltrates exhibited perfusion defects with dye pooling. Retinal pigment
      epithelium detachments (PEDs) demonstrated dynamic filling mechanisms.
      Intraretinal extravasation in retinal vascular disease was detected within a well
      demarcated area with prominent retinal thickening. CONCLUSIONS: Confocal
      topographic angiography allows high-resolution three-dimensional imaging of
      chorioretinal vascular and exudative diseases. Structural vascular changes (e.g.,
      proliferation) are detected in respect to location and size. Dynamic processes
      (e.g., perfusion defects, extravasation, and barrier dysfunction) are clearly
      identified and may be quantified. Topographic angiography is a promising
      technique in the diagnosis, therapeutic evaluation, and pathophysiological
      evaluation of macular disease.

PMID- 11527955
TI  - Mutation of human retinal fascin gene (FSCN2) causes autosomal dominant retinitis
      pigmentosa.
AB  - PURPOSE: To characterize the clinical features of 14 Japanese patients with
      autosomal dominant retinitis pigmentosa (ADRP) who were found to have a mutation
      in the FSCN2 gene. METHODS: Mutation screening by single-strand conformation
      polymorphism (SSCP) was performed in 120 unrelated patients with ADRP, 200
      unrelated patients with autosomal recessive retinitis pigmentosa (ARRP), and 100
      patients with simplex RP (SRP). The DNA fragment that showed abnormal mobility on
      SSCP was sequenced. The clinical features of these patients were determined by
      visual acuity, slit lamp biomicroscopy, electroretinography, fluorescein
      angiography, and kinetic visual field testing. RESULTS: A novel 208delG mutation
      in the FSCN2 gene was identified in 14 patients from four unrelated families with
      ADRP. The ophthalmic findings were typical of RP. CONCLUSIONS: The findings show
      that a 208delG mutation in the FSCN2 gene produces ADRP. This mutation was found
      in 3.3% of the patients with ADRP in Japan, which suggests that it may be
      relatively common in Japanese patients with ADRP.

PMID- 11527956
TI  - Suppression of choroidal neovascularization by adeno-associated virus vector
      expressing angiostatin.
AB  - PURPOSE: To test the efficacy of a recombinant adeno-associated virus (rAAV)
      vector that expresses mouse angiostatin in suppressing experimental choroidal
      neovascularization (CNV) in a rat model. METHODS: An rAAV vector, rAAV
      angiostatin, was constructed to deliver the mouse angiostatin gene. rAAV
      angiostatin and a control virus, rAAV-lacZ, were delivered in vivo by subretinal
      injection in Brown Norway rats, and the delivery was confirmed by reverse
      transcriptase polymerase chain reaction (RT-PCR). For a CNV suppression
      experiment, CNV was generated by fundus krypton laser photocoagulation 7 days
      after the viral vector injection and was evaluated by fluorescein angiography
      (FA) and histology. Apoptosis in retina was analyzed using the TUNEL assay.
      Inflammation in the retina was investigated by immunohistochemistry, using
      antibodies that recognize lymphocytes. RESULTS: rAAV-angiostatin injection led to
      sustained expression of the angiostatin gene in chorioretinal tissue for up to150
      days. FA analysis revealed significant reduction of the average sizes of CNV
      lesions in rAAV-angiostatin-injected eyes when compared with rAAV-lacZ-injected
      eyes at both 14 (P = 0.019) and 150 (P = 0.010) days after injection. Moreover,
      histologic analysis of CNV lesions also revealed significantly smaller lesions in
      rAAV-angiostatin-injected eyes (P = 0.004). As for adverse effects, rAAV
      angiostatin injection did not cause inflammation or apoptosis of cells in retina
      and choroid. CONCLUSIONS: This is the first report that subretinal injection of
      rAAV-angiostatin can significantly reduce the sizes of CNV lesions. This and the
      absence of apoptosis and inflammation in chorioretinal tissue indicate the
      feasibility of a gene therapy approach for treatment of CNV disease.

PMID- 11527957
TI  - VEGF-initiated blood-retinal barrier breakdown in early diabetes.
AB  - PURPOSE: The objectives of this study were to (1) determine whether endogenous
      vascular endothelial growth factor (VEGF) triggers diabetic blood-retinal barrier
      breakdown, and (2) identify the site as well as phenotype of the hyperpermeable
      diabetic retinal vessels. METHODS: Retinal VEGF mRNA levels were quantified in 1
      week diabetic rats using the RNase protection assay. VEGF bioactivity was blocked
      via the systemic administration of a highly specific VEGF-neutralizing soluble
      Flt/F(c) construct (VEGF TrapA(40)). An inactive IL6 receptor/F(c) construct
      (IL6R Trap) was used as an isotype control. Blood-retinal barrier breakdown was
      quantified using the Evans blue technique and was spatially localized with
      fluorescent microspheres. RESULTS: Retinal VEGF mRNA levels in 1-week diabetic
      animals were 3.2-fold higher than in nondiabetic controls (P < 0.0001).
      Similarly, retinal vascular permeability in 8-day diabetic animals was 1.8-fold
      higher than in normal nondiabetic controls (P < 0.05). Diabetes-induced blood
      retinal barrier breakdown was dose-dependently inhibited with VEGF TrapA(40),
      with 25 mg/kg producing complete inhibition of the diabetes-induced increases (P
      < 0.05). Blood-retinal barrier breakdown in diabetic animals treated with solvent
      alone or IL6R Trap did not differ significantly from untreated diabetic animals
      (P > 0.05). Spatially, early blood-retinal barrier breakdown was localized to the
      retinal venules and capillaries of the superficial retinal vasculature.
      CONCLUSIONS: Early blood-retinal barrier breakdown in experimental diabetes is
      VEGF dependent and is restricted, in part, to the venules and capillaries of the
      superficial inner retinal vasculature. VEGF inhibition should prove a useful
      therapeutic approach in the treatment of early diabetic blood-retinal barrier
      breakdown.

PMID- 11527958
TI  - Localization of the alpha(1F) calcium channel subunit in the rat retina.
AB  - PURPOSE: The molecular identity of the calcium channels that mediate glutamate
      release from photoreceptors is unknown. Mutations in the recently identified,
      retina-specific alpha(1F) calcium channel subunit cause incomplete X-linked
      congenital stationary night blindness (CSNB2), the phenotype of which is
      consistent with a defect in neurotransmission within the retina. The purpose of
      this study was to determine the cellular distribution of the alpha(1F) subunit in
      the retina. METHODS: Antibodies were raised against a unique peptide from the
      human alpha(1F) sequence. Rat retina sections were labeled with affinity-purified
      alpha(1F) antibodies and the immunofluorescence analyzed by confocal microscopy.
      The alpha(1F) staining was compared with that obtained with a pan-alpha(1)
      antibody, used to reveal the distribution of known voltage-gated calcium channels
      in the retina. Some sections were double labeled for alpha(1F) and the
      photoreceptor synaptic ribbon marker, bassoon. RESULTS: Staining of retina
      sections with anti-alpha(1F) resulted in strong punctate labeling in the outer
      plexiform layer (OPL) and weak punctate labeling in the inner plexiform layer
      (IPL), consistent with a synaptic localization. Staining was also observed in the
      outer nuclear layer. Within the OPL, alpha(1F) immunoreactivity was clustered in
      discrete, horseshoe-shaped patches, the shape and dimensions of which are
      characteristic of rod active zones. Similar structures were labeled with the pan
      alpha(1) antibody. Localization of alpha(1F) immunoreactivity to rod active zones
      was confirmed by double labeling for bassoon, a component of photoreceptor
      synaptic ribbons. CONCLUSIONS: The distribution of alpha(1F) immunoreactivity in
      the OPL suggests that calcium influx through alpha(1F) or alpha(1F)-like channels
      mediates glutamate release from rod photoreceptors.

PMID- 11527959
TI  - Induction of an aging mRNA retinal pigment epithelial cell phenotype by matrix
      containing advanced glycation end products in vitro.
AB  - PURPOSE: To determine an extensive mRNA phenotype of the established RPE cell
      line ARPE-19 when grown on a matrix modified by advanced glycation end products
      (AGEs). METHODS: Growth Factor Reduced Matrigel (Collaborative Biomedical
      Products, Bedford, MA) was nonenzymatically glycated with glycolaldehyde. ARPE-19
      cells were seeded on both AGE-Matrigel and Matrigel and grown to confluence, and
      serum was withdrawn for 3 days. RNA was extracted, and microarray analysis was
      performed to characterize the genes, which are altered by a matrix modified by
      AGEs. Gene expression changes were confirmed by RT-PCR/Southern and Northern blot
      analysis. Apoptosis was measured by annexin V/propidium iodide labeling. RESULTS:
      Clusters of genes with altered expression were found related to cell
      differentiation, growth factors that regulate the RPE cell and basement membrane,
      and apoptosis. RT-PCR/Southern and Northern blot analysis confirmed the
      expression patterns of selected genes, and flow cytometry showed increased
      annexin V/propidium iodide-labeled cells when grown on AGE-Matrigel. CONCLUSIONS:
      Microarray analysis identified clusters of genes that could promote an aging RPE
      phenotype in vitro induced by a matrix modified with AGEs.

PMID- 11527960
TI  - Role of D-cysteine desulfhydrase in the adaptation of Escherichia coli to D
      cysteine.
AB  - D-cysteine, a powerful inhibitor of Escherichia coli growth, is decomposed in
      vitro into pyruvate, H2S, and NH3 by D-cysteine desulfhydrase. To assess the role
      of this reaction in the adaptation of the bacterium to growth on D-cysteine, the
      gene of the desulfhydrase was cloned. It corresponds to the open reading frame
      yedO at 43.03 min on the genetic map of E. coli. The amino acid sequence deduced
      from this gene is homologous to those of several 1-aminocyclopropane-carboxylate
      deaminases. However, the E. coli desulfhydrase does not use 1-aminocyclopropane-1
      carboxylate as substrate. Various mutants in which the yedO gene was inactivated
      or overexpressed were constructed. They exhibited hypersensitivity or resistance,
      respectively, to the presence of d-cysteine in the culture medium. Growth
      protection against D-cysteine in minimal medium was conferred by the simultaneous
      addition of isoleucine, leucine, and valine. In agreement with this behavior, D
      cysteine inhibited the activity of threonine deaminase, a key enzyme of the
      isoleucine, leucine, and valine pathway. Finally, in the presence of the intact
      yedO gene, E. coli growth was improved by addition of D-cysteine as the sole
      sulfur source. In agreement with a role of the desulfhydrase in sulfur
      metabolism, yedO expression was induced under conditions of sulfate limitation.

PMID- 11527961
TI  - Regulation of beta-catenin function by the IkappaB kinases.
AB  - Both the beta-catenin and the nuclear factor kappaB (NF-kappaB) proteins are
      important regulators of gene expression and cellular proliferation. Two kinases,
      IKKalpha and IKKbeta, are critical activators of the NF-kappaB pathway. Here we
      present evidence that these kinases are also important in the regulation of beta
      catenin function. IKKalpha- and IKKbeta-deficient mouse embryo fibroblasts
      exhibited different patterns of beta-catenin cellular localization. IKKbeta
      decreases beta-catenin-dependent transcriptional activation, while IKKalpha
      increases beta-catenin-dependent transcriptional activity. IKKalpha and IKKbeta
      interact with and phosphorylate beta-catenin using both in vitro and in vivo
      assays. Our results suggest that differential interactions of beta-catenin with
      IKKalpha and IKKbeta may in part be responsible for regulating beta-catenin
      protein levels and cellular localization and integrating signaling events between
      the NF-kappaB and Wingless pathways.

PMID- 11527962
TI  - Structure prediction and active site analysis of the metal binding determinants
      in gamma -glutamylcysteine synthetase.
AB  - gamma-Glultamylcysteine synthetase (gamma-GCS) catalyzes the first step in the de
      novo biosynthesis of glutathione. In trypanosomes, glutathione is conjugated to
      spermidine to form a unique cofactor termed trypanothione, an essential cofactor
      for the maintenance of redox balance in the cell. Using extensive similarity
      searches and sequence motif analysis we detected homology between gamma-GCS and
      glutamine synthetase (GS), allowing these proteins to be unified into a
      superfamily of carboxylate-amine/ammonia ligases. The structure of gamma-GCS,
      which was previously poorly understood, was modeled using the known structure of
      GS. Two metal-binding sites, each ligated by three conserved active site residues
      (n1: Glu-55, Glu-93, Glu-100; and n2: Glu-53, Gln-321, and Glu-489), are
      predicted to form the catalytic center of the active site, where the n1 site is
      expected to bind free metal and the n2 site to interact with MgATP. To elucidate
      the roles of the metals and their ligands in catalysis, these six residues were
      mutated to alanine in the Trypanosoma brucei enzyme. All mutations caused a
      substantial loss of activity. Most notably, E93A was able to catalyze the l-Glu
      dependent ATP hydrolysis but not the peptide bond ligation, suggesting that the
      n1 metal plays an important role in positioning l-Glu for the reaction chemistry.
      The apparent K(m) values for ATP were increased for both the E489A and Q321A
      mutant enzymes, consistent with a role for the n2 metal in ATP binding and
      phosphoryl transfer. Furthermore, the apparent K(d) values for activation of
      E489A and Q321A by free Mg(2+) increased. Finally, substitution of Mn(2+) for
      Mg(2+) in the reaction rescued the catalytic deficits caused by both mutations,
      demonstrating that the nature of the metal ligands plays an important role in
      metal specificity.

PMID- 11527963
TI  - A defect in the cytochrome b large subunit in complex II causes both superoxide
      anion overproduction and abnormal energy metabolism in Caenorhabditis elegans.
AB  - A mev-1(kn1) mutant of the nematode Caenorhabditis elegans is defective in the
      cytochrome b large subunit (Cyt-1/ceSDHC) in complex II of the mitochondrial
      electron transport chain. We have previously shown that a mutation in mev-1
      causes shortened life span and rapid accumulation of aging markers such as
      fluorescent materials and protein carbonyls in an oxygen-dependent fashion.
      However, it remains unclear as to whether this hypersensitivity is caused by
      direct toxicity of the exogenous oxygen or by the damage of endogenous reactive
      oxygen species derived from mitochondria. Here we report important biochemical
      changes in mev-1 animals that serve to explain their abnormalities under normoxic
      conditions: (i) an overproduction of superoxide anion from mitochondria; and (ii)
      a reciprocal reduction in glutathione content even under atmospheric oxygen. In
      addition, unlike wild type, the levels of superoxide anion production from mev-1
      mitochondria were significantly elevated under hyperoxia. Under normal
      circumstances, it is well known that superoxide anion is produced at complexes I
      and III in the electron transport system. Our data suggest that the mev-1(kn1)
      mutation increases superoxide anion production at complex II itself rather than
      at complexes I and III. The mev-1 mutant also had a lactate level 2-fold higher
      than wild type, indicative of lactic acidosis, a hallmark of human mitochondrial
      diseases. These data indicate that Cyt-1/ceSDHC plays an important role not only
      in energy metabolism but also in superoxide anion production that is critically
      involved in sensitivity to atmospheric oxygen.

PMID- 11527964
TI  - Crystal structure of Bruton's tyrosine kinase domain suggests a novel pathway for
      activation and provides insights into the molecular basis of X-linked
      agammaglobulinemia.
AB  - Bruton's tyrosine kinase is intimately involved in signal transduction pathways
      regulating survival, activation, proliferation, and differentiation of B lineage
      lymphoid cells. Mutations in the human btk gene are the cause of X-linked
      agammaglobulinemia, a male immune deficiency disorder characterized by a lack of
      mature, immunoglobulin-producing B lymphocytes. We have determined the x-ray
      crystal structure of the Bruton's tyrosine kinase kinase domain in its
      unphosphorylated state to a 2.1 A resolution. A comparison with the structures of
      other tyrosine kinases and a possible mechanism of activation unique to Bruton's
      tyrosine kinase are provided.

PMID- 11527965
TI  - Multimerization of phosphorylated and non-phosphorylated ArcA is necessary for
      the response regulator function of the Arc two-component signal transduction
      system.
AB  - To adapt to anaerobic conditions, Escherichia coli operates the Arc two-component
      signal transduction system, consisting of a sensor kinase, ArcB, and a response
      regulator, ArcA. ArcA is converted to the active form, phosphorylated ArcA (ArcA
      P), by ArcB-mediated phosphorylation. The active ArcA-P binds to the promoter
      regions of target genes, thereby regulating their transcriptional activities. The
      phosphoryl group of ArcA-P is unstable with a half-life of 30 min. However, we
      were able to inhibit the dephosphorylation for more than 12 h by the addition of
      EDTA; this allowed us to characterize ArcA-P. Gel-filtration and glycerol
      sedimentation experiments demonstrated that ArcA exists as a homo-dimer. ArcA
      phosphorylated by either ArcB or carbamyl phosphate multimerizes to form a
      tetramer of dimers; this multimer binds to the ArcA DNA binding site. Isoelectric
      focusing gel electrophoresis and nitrocellulose-filter binding analyses indicated
      that the ArcA multimer is composed of both ArcA-P and ArcA in a ratio, 1:1. The
      ArcA(D54E) mutant protein was unable to be phosphorylated by ArcB. This defect
      resulted in the inability of ArcA(D54E) to form a multimer or to bind to the ArcA
      DNA binding site. These results indicate that phosphorylation of ArcA induces
      multimerization prior to DNA binding, and the multimerization is a prerequisite
      for binding. Our results suggest a novel model that phosphorylation of ArcA by
      ArcB regulates multimerization of ArcA, which in turn functions as a response
      regulator.

PMID- 11527966
TI  - The small conductance K+ channel, KCNQ1: expression, function, and subunit
      composition in murine trachea.
AB  - The gene KCNQ1 encodes a K(+) channel alpha-subunit important for cardiac
      repolarization, formerly known as K(v)LQT1. In large and small intestine a
      channel complex consisting of KCNQ1 and the beta-subunit KCNE3 (MiRP2) is known
      to mediate the cAMP-activated basolateral K(+) current, which is essential for
      luminal Cl(-) secretion. Northern blot experiments revealed an expression of both
      subunits in lung tissue. However, previous reports suggested a role of KCNE1
      (minK, Isk) but not KCNE3 in airway epithelial cells. Here we give evidence that
      KCNE1 is not detected in murine tracheal epithelial cells and that Cl(-)
      secretion by these cells is not reduced by the knock-out of the KCNE1 gene. In
      contrast we show that a complex consisting of KCNQ1 and KCNE3 probably forms a
      basolateral K(+) channel in murine tracheal epithelial cells. As described for
      colonic epithelium, the current through KCNQ1 complexes in murine trachea is
      specifically inhibited by the chromanol 293B. A 293B-sensitive current was
      present after stimulation with forskolin and agonists that increase Ca(2+) as
      well as after administration of the pharmacological K(+) channel activator, 1
      EBIO. A 293B-inhibitable current was already present under control conditions and
      reduced after administration of amiloride indicating a role of this K(+) channel
      not only for Cl(-) secretion but also for Na(+) reabsorption. We conclude that at
      least in mice a KCNQ1 channel complex seems to be the dominant basolateral K(+)
      conductance in tracheal epithelial cells.

PMID- 11527967
TI  - Engineered Zn(2+) switches in the gamma-aminobutyric acid (GABA) transporter-1.
      Differential effects on GABA uptake and currents.
AB  - Two high affinity Zn(2+) binding sites were engineered in the otherwise Zn(2+)
      insensitive rat gamma-aminobutyric acid (GABA) transporter-1 (rGAT-1) based on
      structural information derived from Zn(2+) binding sites engineered previously in
      the homologous dopamine transporter. Introduction of a histidine (T349H) at the
      extracellular end of transmembrane segment (TM) 7 together with a histidine
      (E370H) or a cysteine (Q374C) at the extracellular end of TM 8 resulted in potent
      inhibition of [3H]GABA uptake by Zn(2+) (IC(50) = 35 and 44 microM,
      respectively). Upon expression in Xenopus laevis oocytes it was similarly
      observed that Zn(2+) was a potent inhibitor of the GABA-induced current (IC(50) =
      21 microM for T349H/E370H and 51 microM for T349H/Q374C), albeit maximum
      inhibition was only approximately 40% in T349H/E370H versus approximately 90% in
      T349H/Q374C. In the wild type, Zn(2+) did not affect the Na(+)-dependent
      transient currents elicited by voltage jumps and thought to reflect capacitive
      charge movements associated with Na(+) binding. However, in both mutants Zn(2+)
      caused a reduction of the inward transient currents upon jumping to
      hyperpolarized potentials as reflected in rightward-shifted Q/V relationships.
      This suggests that Zn(2+) is inhibiting transporter function by stabilizing the
      outward-facing Na(+)-bound state. Translocation of lithium by the transporter
      does not require GABA binding and analysis of this uncoupled Li(+) conductance
      revealed a potent inhibition by Zn(2+) in T349H/E370H, whereas surprisingly the
      T349H/Q374C leak was unaffected. This differential effect supports that the leak
      conductance represents a unique operational mode of the transporter involving
      conformational changes different from those of the substrate translocation
      process. Altogether our results support both an evolutionary conserved structural
      organization of the TM 7/8 domain and a key role of this domain in GABA-dependent
      and -independent conformational changes of the transporter.

PMID- 11527968
TI  - Erythrocyte ankyrin promoter mutations associated with recessive hereditary
      spherocytosis cause significant abnormalities in ankyrin expression.
AB  - Ankyrin defects are the most common cause of hereditary spherocytosis (HS). In
      several kindreds with recessive, ankyrin-deficient HS, mutations have been
      identified in the ankyrin promoter that have been proposed to decrease ankyrin
      synthesis. We analyzed the effects of two mutations, -108T to C and -108T to C in
      cis with -153G to A, on ankyrin expression. No difference between wild type and
      mutant promoters was demonstrated in transfection or gel shift assays in vitro.
      Transgenic mice with a wild type ankyrin promoter linked to a human (A)gamma
      globin gene expressed gamma-globin in 100% of erythrocytes in a copy number
      dependent, position-independent manner. Transgenic mice with the mutant -108
      promoter demonstrated variegated gamma-globin expression, but showed copy number
      dependent and position-independent expression similar to wild type. Severe
      effects in ankyrin expression were seen in mice with the linked -108/-153
      mutations. Three transgenic lines had undetectable levels of (A)gamma-globin
      mRNA, indicating position-dependent expression, and four lines expressed
      significantly lower levels of (A)gamma-globin mRNA than wild type. Two of four
      expressing lines showed variegated gamma-globin expression, and there was no
      correlation between transgene copy number and RNA level, indicating copy number
      independent expression. These data are the first demonstration of functional
      defects caused by HS-related, ankyrin gene promoter mutations.

PMID- 11527969
TI  - Substrate specificities of recombinant mannan-binding lectin-associated serine
      proteases-1 and -2.
AB  - Mannan-binding lectin (MBL)-associated serine proteases-1 and 2 (MASP-1 and MASP
      2) are homologous modular proteases that each interact with MBL, an oligomeric
      serum lectin involved in innate immunity. To precisely determine their substrate
      specificity, human MASP-1 and MASP-2, and fragments from their catalytic regions
      were expressed using a baculovirus/insect cells system. Recombinant MASP-2
      displayed a rather wide, C1s-like esterolytic activity, and specifically cleaved
      complement proteins C2 and C4, with relative efficiencies 3- and 23-fold higher,
      respectively, than human C1s. MASP-2 also showed very weak C3 cleaving activity.
      Recombinant MASP-1 had a lower and more restricted esterolytic activity. It
      showed marginal activity toward C2 and C3, and no activity on C4. The enzymic
      activity of both MASP-1 and MASP-2 was specifically titrated by C1 inhibitor, and
      abolished at a 1:1 C1 inhibitor:protease ratio. Taken together with previous
      findings, these and other data strongly support the hypothesis that MASP-2 is the
      protease that, in association with MBL, triggers complement activation via the
      MBL pathway, through combined self-activation and proteolytic properties devoted
      to C1r and C1s in the C1 complex. In view of the very low activity of MASP-1 on
      C3 and C2, our data raise questions about the implication of this protease in
      complement activation.

PMID- 11527970
TI  - Rotenone inhibits the mitochondrial permeability transition-induced cell death in
      U937 and KB cells.
AB  - The permeability transition pore (PTP) is a mitochondrial inner membrane Ca(2+)
      sensitive channel that plays a key role in different models of cell death.
      Because functional links between the PTP and the respiratory chain complex I have
      been reported, we have investigated the effects of rotenone on PTP regulation in
      U937 and KB cells. We show that rotenone was more potent than cyclosporin A at
      inhibiting Ca(2+)-induced PTP opening in digitonin-permeabilized cells energized
      with succinate. Consistent with PTP regulation by electron flux through complex
      I, the effect of rotenone persisted after oxidation of pyridine nucleotides by
      duroquinone. tert-butyl hydroperoxide induced PTP opening in intact cells (as
      shown by mitochondrial permeabilization to calcein and cobalt), as well as
      cytochrome c release and cell death. All these events were prevented by rotenone
      or cyclosporin A. These data demonstrate that respiratory chain complex I plays a
      key role in PTP regulation in vivo and confirm the importance of PTP opening in
      the commitment to cell death.

PMID- 11527971
TI  - Constitutive MEK/MAPK activation leads to p27(Kip1) deregulation and antiestrogen
      resistance in human breast cancer cells.
AB  - Antiestrogens, such as the drug tamoxifen, inhibit breast cancer growth by
      inducing cell cycle arrest. Antiestrogens require action of the cell cycle
      inhibitor p27(Kip1) to mediate G1 arrest in estrogen receptor-positive breast
      cancer cells. We report that constitutive activation of the mitogen-activated
      protein kinase (MAPK) pathway alters p27 phosphorylation, reduces p27 protein
      levels, reduces the cdk2 inhibitory activity of the remaining p27, and
      contributes to antiestrogen resistance. In two antiestrogen-resistant cell lines
      that showed increased MAPK activation, inhibition of the MAPK kinase (MEK) by
      addition of U0126 changed p27 phosphorylation and restored p27 inhibitory
      function and sensitivity to antiestrogens. Using antisense p27 oligonucleotides,
      we demonstrated that this restoration of antiestrogen-mediated cell cycle arrest
      required p27 function. These data suggest that oncogene-mediated MAPK activation,
      frequently observed in human breast cancers, contributes to antiestrogen
      resistance through p27 deregulation.

PMID- 11527972
TI  - Hyaluronan binding and degradation by Streptococcus agalactiae hyaluronate lyase.
AB  - Streptococcus agalactiae hyaluronate lyase is a virulence factor that helps this
      pathogen to break through the biophysical barrier of the host tissues by the
      enzymatic degradation of hyaluronan and certain chondroitin sulfates at beta-1,4
      glycosidic linkages. Crystal structures of the native enzyme and the enzyme
      product complex were determined at 2.1- and 2.2-A resolutions, respectively. An
      elongated cleft transversing the middle of the molecule has been identified as
      the substrate-binding place. Two product molecules of hyaluronan degradation were
      observed bound to the cleft. The enzyme catalytic site was identified to comprise
      three residues: His(479), Tyr(488), and Asn(429). The highly positively charged
      cleft facilitates the binding of the negatively charged polymeric substrate
      chain. The matching between the aromatic patch of the enzyme and the hydrophobic
      patch of the substrate chain anchors the substrate chain into degradation
      position. A pair of proton exchanges between the enzyme and the substrate results
      in the cleavage of the beta-1,4 glycosidic linkage of the substrate chain and the
      unsaturation of the product. Phe(423) likely determines the size of the product
      at the product release side of the catalytic region. Hyaluronan chain is
      processively degraded from the reducing end toward the nonreducing end. The
      unsulfated or 6-sulfated regions of chondroitin sulfate can also be degraded in
      the same manner as hyaluronan.

PMID- 11527973
TI  - Isolation and characterization of a folate receptor mRNA-binding trans-factor
      from human placenta. Evidence favoring identity with heterogeneous nuclear
      ribonucleoprotein E1.
AB  - The interaction of an 18-base cis-element in the 5'-untranslated region of human
      folate receptor (FR)-alpha mRNA with a cytosolic trans-factor protein is critical
      for the translation of FR (Sun, X.-L., and Antony, A. C. (1996) J. Biol. Chem.
      271, 25539-25547). This trans-factor was isolated to apparent homogeneity as a 43
      and 38-kDa doublet from human placenta using poly(U)-Sepharose, followed by
      preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis and electro
      elution as major purification steps. Amino acid microsequencing of two cyanogen
      bromide-generated peptide fragments of the 43-kDa trans-factor revealed complete
      identity with 43-kDa heterogeneous nuclear ribonucleoprotein E1 (hnRNP E1).
      Purified specific rabbit anti-hnRNP E1 peptide antibodies (generated against a
      synthetic oligopeptide that was not represented in microsequenced peptides of the
      trans-factor) also recognized the purified trans-factor on Western blots.
      Conversely, the 18-base FR RNA cis-element also bound hnRNP E1 protein on
      Northwestern blots. Moreover, a 19-base RNA cis-element in the 3'-untranslated
      region of 15-lipoxygenase mRNA that is known to bind hnRNP E1 also interacted
      with placental 43-kDa trans-factor. In addition, several murine tissues
      containing a hnRNP E1-related protein (also known as alphaCP-1) readily
      interacted with the 18-base FR RNA cis-element. Finally, anti-hnRNP E1 antibodies
      specifically inhibited translation of FR in vitro in a dose-dependent manner, and
      the antibody effect could be reversed in a dose-dependent manner by either
      purified trans-factor or hnRNP E1. Collectively, the data favor identity of the
      FR mRNA-binding trans-factor and hnRNP E1, confirm its critical role in the
      translation of FR, and highlight yet another role of multifunctional hnRNP E1 in
      eukaryotic mRNA regulation.

PMID- 11527974
TI  - Mutant prion proteins are partially retained in the endoplasmic reticulum.
AB  - Familial prion diseases are linked to point and insertional mutations in the
      prion protein (PrP) gene that are presumed to favor conversion of the cellular
      isoform of PrP to the infectious isoform. In this report, we have investigated
      the subcellular localization of PrP molecules carrying pathogenic mutations using
      immunofluorescence staining, immunogold labeling, and PrP-green fluorescent
      protein chimeras. To facilitate visualization of the mutant proteins, we have
      utilized a novel Sindbis viral replicon engineered to produce high protein levels
      without cytopathology. We demonstrate that several different pathogenic mutations
      have a common effect on the trafficking of PrP, impairing delivery of the
      molecules to the cell surface and causing a portion of them to accumulate in the
      endoplasmic reticulum. These observations suggest that protein quality control in
      the endoplasmic reticulum may play an important role in prion diseases, as it
      does in some other inherited human disorders. Our experiments also show that
      chimeric PrP molecules with the sequence of green fluorescent protein inserted
      adjacent to the glycolipidation site are post-translationally modified and
      localized normally, thus documenting the utility of these constructs in cell
      biological studies of PrP.

PMID- 11527975
TI  - Design and characterization of a highly selective peptide inhibitor of the small
      conductance calcium-activated K+ channel, SkCa2.
AB  - Apamin-sensitive small conductance calcium-activated potassium channels (SKCa1-3)
      mediate the slow afterhyperpolarization in neurons, but the molecular identity of
      the channel has not been defined because of the lack of specific inhibitors. Here
      we describe the structure-based design of a selective inhibitor of SKCa2.
      Leiurotoxin I (Lei) and PO5, peptide toxins that share the RXCQ motif, potently
      blocked human SKCa2 and SKCa3 but not SKCa1, whereas maurotoxin, Pi1, Tskappa,
      and PO1 were ineffective. Lei blocked these channels more potently than PO5
      because of the presence of Ala(1), Phe(2), and Met(7). By replacing Met(7) in the
      RXCQ motif of Lei with the shorter, unnatural, positively charged diaminobutanoic
      acid (Dab), we generated Lei-Dab(7), a selective SKCa2 inhibitor (K(d) = 3.8 nm)
      that interacts with residues in the external vestibule of the channel. SKCa3 was
      rendered sensitive to Lei-Dab(7) by replacing His(521) with the corresponding
      SKCa2 residue (Asn(367)). Intracerebroventricular injection of Lei-Dab(7) into
      mice resulted in no gross central nervous system toxicity at concentrations that
      specifically blocked SKCa2 homotetramers. Lei-Dab(7) will be a useful tool to
      investigate the functional role of SKCa2 in mammalian tissues.

PMID- 11527976
TI  - A Cdc28 mutant uncouples G1 cyclin phosphorylation and ubiquitination from G1
      cyclin proteolysis.
AB  - Proteolysis of the yeast G(1) cyclins is triggered by their Cdc28-dependent
      phosphorylation. Phosphorylated Cln1 and Cln2 are ubiquitinated by the SCF-Grr1
      complex and then degraded by the 26 S proteasome. In this study, we identified a
      cak1 allele in a genetic screen for mutants that stabilize the yeast G(1)
      cyclins. Further characterization showed that Cln2HA was hypophosphorylated,
      unable to bind Cdc28, and stabilized in cak1 mutants at the restrictive
      temperature. Hypophosphorylation of Cln2HA could thus explain its stabilization.
      To test this possibility, we expressed a Cak1-independent mutant of Cdc28 (Cdc28
      43244) in cak1 mutants and found that Cln2HA phosphorylation was restored, but
      surprisingly, the phospho-Cln2HA was stabilized. When bound to Cdc28-43244,
      Cln2HA was recognized and polyubiquitinated by SCF-Grr1. The Cdc28-43244 mutant
      thus reveals an unexpected complexity in the degradation of polyubiquitinated
      Cln2HA by the proteasome.

PMID- 11527977
TI  - Regulation of matrilysin expression in airway epithelial cells by Pseudomonas
      aeruginosa flagellin.
AB  - Matrilysin (matrix metalloproteinase-7) is expressed by mucosal epithelia
      throughout the body and functions in host defense by activating murine intestinal
      alpha-defensins. In normal adult human lung, matrilysin is expressed at low
      levels in the airway epithelium, but is markedly up-regulated in cystic fibrosis
      (CF). Because CF lungs support a heavy bacterial load, we assessed if relevant CF
      pathogens regulate matrilysin expression in human lung epithelial cells. Indeed,
      acute infection with Pseudomonas aeruginosa (but not Staphylococcus aureus,
      Haemophilus influenzae, or Klebsiella pneumoniae) induced the expression of
      matrilysin in Calu-3 lung epithelial cells. Increased matrilysin mRNA levels were
      detectable at 3 h post-infection and peaked at a 25-fold induction between 6 and
      8 h. Both P. aeruginosa CF isolates and laboratory strains induced matrilysin
      expression to similar levels. Flagellin, the monomeric precursor of bacterial
      flagella, was identified as the inductive factor released by P. aeruginosa that
      regulated matrilysin expression. In addition, flagellin-null mutants failed to
      stimulate matrilysin expression in cultured cells or in lungs infected in vivo.
      These data show that P. aeruginosa (and specifically flagellin) potently
      stimulates matrilysin expression in lung epithelial cells and may mediate the
      overexpression of this proteinase in CF lungs.

PMID- 11527978
TI  - Novel RNA-binding properties of Pop3p support a role for eukaryotic RNase P
      protein subunits in substrate recognition.
AB  - Ribonuclease P (RNase P) catalyzes the 5'-end maturation of transfer RNA
      molecules. Recent evidence suggests that the eukaryotic protein subunits may
      provide substrate-binding functions (True, H. L., and Celander, D. W. (1998) J.
      Biol. Chem. 273, 7193-7196). We now report that Pop3p, an essential protein
      subunit of the holoenzyme in Saccharomyces cerevisiae, displays novel RNA-binding
      properties. A recombinant form of Pop3p (H6Pop3p) displays a 3-fold greater
      affinity for binding pre-tRNA substrates relative to tRNA products. The
      recognition sequence for the H6Pop3p-substrate interaction in vitro was mapped to
      a 39-nucleotide long sequence that extends from position -21 to +18 surrounding
      the natural processing site in pre-tRNA substrates. H6Pop3p binds a variety of
      RNA molecules with high affinity (K(d) = 16-25 nm) and displays a preference for
      single-stranded RNAs. Removal or modification of basic C-terminal residues
      attenuates the RNA-binding properties displayed by the protein specifically for a
      pre-tRNA substrate. These studies support the model that eukaryotic RNase P
      proteins bind simultaneously to the RNA subunit and RNA substrate.

PMID- 11527979
TI  - Functional analysis of chimeric proteins of the Wilson Cu(I)-ATPase (ATP7B) and
      ZntA, a Pb(II)/Zn(II)/Cd(II)-ATPase from Escherichia coli.
AB  - ATP7B, the Wilson disease-associated Cu(I)-transporter, and ZntA from Escherichia
      coli are soft metal P1-type ATPases with mutually exclusive metal ion substrates.
      P1-type ATPases have a distinctive amino-terminal domain containing the conserved
      metal-binding motif GXXCXXC. ZntA has one copy of this motif while ATP7B has six
      copies. The effect of interchanging the amino-terminal domains of ATP7B and ZntA
      was investigated. Chimeric proteins were constructed in which either the entire
      amino-terminal domain of ATP7B or only its sixth metal-binding motif replaced the
      amino-terminal domain of ZntA. Both chimeras conferred resistance to lead, zinc,
      and cadmium salts but not to copper salts. The purified chimeras displayed
      activity with lead, cadmium, zinc, and mercury, which are substrates of ZntA.
      There was no activity with copper or silver, which are substrates of ATP7B. The
      chimeras were 2-3-fold less active than ZntA. Thus, the amino-terminal domain of
      P1-type ATPases cannot alter the metal specificity determined by the
      transmembrane segment. Also, these results suggest that this domain interacts
      with the rest of the transporter in a metal ion-specific manner; the amino
      terminal domain of ATP7B cannot replace that of ZntA in restoring full catalytic
      activity.

PMID- 11527980
TI  - High affinity association of myo-inositol trisphosphates with phytase and its
      effect upon the catalytic potential of the enzyme.
AB  - A neutral phytase from germinating mung bean (Vigna radiata) seeds
      dephosphorylates myo-inositol hexakisphosphate sequentially to myo-inositol. The
      enzyme also binds with higher affinity to myo-inositol trisphosphates (1,4,5),
      (2,4,5), and (1,3,4) isomers without catalysis. The high affinity complex elicits
      Ca(2+) mobilization in vitro from microsomes/vacuoles via the formation of a
      ternary complex with the receptor for Ins(1,4,5)P(3). As a sequel to our previous
      report, we have carried out a detailed characterization of the two sites and
      examined the mutual interactions between them. Presaturation of the high affinity
      site leads to an increase in the affinity of the enzyme for phytic acid and its
      rate of dephosphorylation as well. From the products of limited tryptic cleavage
      of phytase, two peptides, each with one activity, have been isolated. The larger
      peptide ( approximately 66 kDa) contains the catalytic site, and the smaller
      peptide ( approximately 5 kDa) has the high affinity myo-inositol trisphosphate
      binding site. The interaction between the dual activities of phytase has been
      observed also at the level of the two peptides. A sequence homology search using
      N-terminal 12 amino acid residues of the 5-kDa fragment has revealed significant
      homology with the Homer class of proteins implicated in signaling pathways
      involving metabotropic glutamate receptor and myo-inositol 1,4,5-trisphosphate
      receptor. These results indicate a second role of phytase in Ca(2+) mobilization
      during germination of mung been seed via a salvage pathway that involves
      allosteric activation by myo-inositol trisphosphate.

PMID- 11527981
TI  - The biology and enzymology of protein N-myristoylation.

PMID- 11527982
TI  - Regulation of hematopoiesis by gap junction-mediated intercellular communication.
AB  - Gap junctions are intercellular channels formed by individual structural units
      known as connexins (Cx) that allow the intercellular exchange of small molecules
      between cells. The presence of Cx protein in bone marrow and thymic stromal cells
      and the demonstration that these cells are functionally coupled have led to the
      hypothesis that groups of stromal cells in the bone marrow and thymus form a
      functional syncytium through which their hematopoietic support capacity is
      coordinated. The validity of this hypothesis was recently tested in a newly
      developed strain of mice in which the gene encoding Cx43, the principal Cx
      expressed in hematopoietic tissues, was disrupted. Studies of myelopoiesis and
      lymphopoiesis in these Cx43-deficient mice revealed that expression of Cx43 in
      the bone marrow and thymus is critically important during periods of active
      hematopoiesis, such as during embryogenesis and after recovery from cytoablative
      treatments. The clinical implications of these observations, as well as issues
      that remain to be addressed to understand the mechanism(s) by which gap junctions
      regulate hematopoiesis, are addressed.

PMID- 11527983
TI  - Negative regulation of cytokine signaling.
AB  - Cytokines use complex signaling cascades to elicit their biological effects, many
      of which involve phosphorylation as a mechanism of activation. Rapid and
      efficient attenuation of cytokine signals is crucial to maintaining regulation of
      these processes and to preventing toxic side effects. Phosphatases have been
      shown to be involved in these regulatory processes, but more recent research has
      seen the discovery of two new families of negative regulators, the suppressor of
      cytokine signaling (SOCS) and protein inhibitors of signal transducer and
      activator of transcription (STAT) (PIAS) protein families. SOCS proteins are
      induced by and inhibit many cytokine-signaling systems in a classic negative
      feedback loop, and the generation of transgenic and knockout models has greatly
      increased our understanding of their physiological functions. PIAS proteins
      interact with the transcriptional mediators of cytokine action, the STATs, to
      suppress their DNA-binding activity. These three classes of molecules form what
      is now emerging as an integrated system for deactivating cytokine signaling at a
      number of levels, from the receptor to the transcription factor.

PMID- 11527984
TI  - Hemofiltrate CC chemokines with unique biochemical properties: HCC-1/CCL14a and
      HCC-2/CCL15.
AB  - The hemofiltrate CC chemokines CCL14a (formerly HCC-1), CCL14b (formerly HCC-3),
      and CCL15 (formerly HCC-2) are encoded by mono- as well as bicistronic
      transcripts from a tandem gene arrangement on human chromosome 17q11.2. The
      transcription and splicing into several mono- and bicistronic transcripts of this
      gene complex are unique for human genes. No corresponding mechanism is known in
      nonprimate mammalian species such as mice and rats. The extremely high
      concentration of CCL14a in human plasma is exceptional for chemokines and led to
      the identification of this chemokine. Several molecular forms of CCL14a have been
      isolated and investigated. The mature propeptide CCL14a(1-74) is a low-affinity
      agonist of CCR1 which is converted to a high-affinity agonist of CCR1 and CCR5 on
      proteolytic processing by serine proteases. In contrast, CCL15 is characterized
      using molecular forms deduced from the mRNA/cDNA and shown to activate cells via
      CCR1 and CCR3, also dependent on the amino-terminal length. Hemofiltrate CC
      chemokines are chemoattractants for different types of leukocytes including
      monocytes, eosinophils, T cells, dendritic cells, and neutrophils. In this
      review, we emphasize the genomic organization, expression patterns, and
      biochemical properties of CCL14a, CCL14b, and CCL15. We report results of
      significance for the development of therapeutic strategies, especially concerning
      HIV infection and inflammatory diseases.

PMID- 11527985
TI  - Activation of human neutrophils in vitro and dieldrin-induced neutrophilic
      inflammation in vivo.
AB  - Many chemicals of environmental concern are known to alter the immune system and
      are considered toxic molecules because they affect immune cell functions.
      Inflammation related to environmental chemical exposure, however, is poorly
      documented, except that from air pollutants. In this study, we found that the
      organochlorine insecticide dieldrin could not alter the ability of human
      neutrophils to phagocytose opsonized sheep red blood cells at nonnecrotic
      concentrations (0.1, 1, 10, and 50 microM). However, dieldrin was found to
      increase human neutrophil superoxide production, RNA synthesis, and
      proinflammatory cytokine interleukin-8 production. The normal apoptotic rate of
      neutrophils evaluated by both cytology and flow cytometry (CD-16 staining) was
      not altered by dieldrin treatments, and this was correlated with its inability to
      inhibit spreading of neutrophils onto glass. Using the murine air pouch model, we
      found that dieldrin induces a neutrophilic inflammation. Taken together, these
      results demonstrated that dieldrin is a proinflammatory contaminant. To our
      knowledge, this is the first report establishing that dieldrin is a contaminant
      exhibiting proinflammatory properties. In addition, it is the first time that the
      murine air pouch model has been successfully used to confirm that a chemical of
      environmental concern can induce an inflammatory response in vivo.

PMID- 11527986
TI  - Monocyte chemoattractant protein-1 enhances HSV-induced encephalomyelitis by
      stimulating Th2 responses.
AB  - Monocyte chemoattractant protein (MCP)-1 has a pathogenic role in herpesvirus
      induced encephalomyelitis (HSM). Anti-MCP-1 antibody greatly decreased HSM
      severity in mice infected with herpes simplex virus type 2 (HSM mice), compared
      with its effect in control HSM mice treated with rabbit immunoglobulin. HSM
      severity was markedly enhanced in mice previously treated with a mixture of
      interleukin (IL) 4 and -10. In response to stimulation with antigen, HSM mouse
      cells isolated from cerebrospinal fluids (CSF cells) produced IL-4 in culture
      fluids; however, IL-4 production decreased in CSF cells derived from HSM mice
      previously treated with anti-MCP-1 antibody. A macrophage population isolated in
      CSF cells from HSM mice (CSF-Mphi) produced MCP-1 in culture fluids. In response
      to stimulation with herpesvirus antigen, a population of T cells isolated from
      CSF cells from HSM mice (CSF-T cells) produced IL-4 into their culture fluids,
      although MCP-1 was not produced by CSF-T cells stimulated by this antigen. IL-4
      production by CSF-T cells was markedly enhanced when they were stimulated with
      viral antigen in the presence of murine recombinant MCP-1 (rMCP-1). Furthermore,
      IL-4 was produced in naive splenic T cells cocultured with CSF-Mphi. These
      results indicate that the severity of HSM is influenced by MCP-1, which
      stimulates Th2 responses.

PMID- 11527987
TI  - Monophosphoryl lipid A stimulated up-regulation of reactive oxygen intermediates
      in human monocytes in vitro.
AB  - The production of reactive oxygen and nitrogen intermediates is a common response
      to infectious challenge in vivo. These agents have been implicated in the
      modulation of cytokine responses and are produced in large amounts in response to
      endotoxins produced by a number of infectious agents. The antigen-presenting cell
      activation caused by these lipopolysacchardies (LPS) has been exploited in the
      use of these agents as adjuvants. In recent years, less-toxic derivatives have
      been sought. One such agent, monophosphoryl lipid A (MPL), has been used
      increasingly in vivo as an adjuvant and as a modulator of the inflammatory
      process. It is known that this agent modulates the inflammatory response and
      cytokine production. In addition, we have shown its effect on the production of
      reactive nitrogen intermediates. In this paper, we show that MPL stimulates the
      release of high levels of superoxide (O(2)(-)) and hydrogen peroxide (H(2)O(2)),
      the latter being greater than that seen with LPS and appearing to be related to
      the inability of MPL to stimulate catalase activity. When cells were pretreated
      with LPS or MPL and subsequently challenged with LPS, the production of O(2)(-)
      and H(2)O(2) was inhibited significantly by LPS and MPL. The concentration of MPL
      required to induce significant hyporesponsiveness to subsequent LPS challenge was
      10 times lower than that of LPS. Hyporesponsiveness was greatest when induced by
      10 microg/ml MPL, the same concentration that induced the maximum release of
      H(2)O(2) in primary stimulation. In addition, we have shown that following MPL
      pretreatment, LPS stimulation does not cause the loss of cytoplasmic
      IkappaBalpha, which occurs when human monocytes are cultured with LPS. From our
      results, we propose a model for the reduced toxicity of MPL.

PMID- 11527988
TI  - Muramyl dipeptide and mononuclear cell supernatant induce Langhans-type cells
      from human monocytes.
AB  - Muramyl dipeptide (MDP) in bacterial cell walls reportedly evokes epithelioid
      cell granulomas. We examined its effects on multinucleated-giant-cell (MGC)
      formation from monocytes. Supernatant of concanavalin A-stimulated peripheral
      blood mononuclear cells (conditioned medium) generated MGCs from monocytes. MDP
      significantly increased the fusion index of Langhans-type MGCs (LGCs) but did not
      affect total MGCs. N-Acetylmuramyl-L-alanyl-L-isoglutamine, an MDP analogue, had
      no effect on MGC formation. MGCs were produced by conditioned medium from
      CD14(++)/CD16(-) monocytes. MDP enhanced the LGC fusion index from CD14(++)/CD16(
      ) monocytes. MGCs were not produced from CD14(+)/CD16(+) monocytes or immature
      dendritic cells induced by granulocyte macrophage-colony stimulating factor (GM
      CSF) and interleukin (IL) 4 and only weakly produced from macrophage (M)-CSF- or
      GM-CSF-induced macrophages. Added MDP did not generate MGCs from CD14(+)/CD16(+)
      monocytes or dendritic cells but enhanced LGC formation from macrophages. Because
      IFN-gamma, IL-3, and GM-CSF reportedly are important in LGC induction, we added
      anti-IFN-gamma, anti-IL-3, or anti-GM-CSF monoclonal antibody (mAb) concomitantly
      to the monocyte culture treated with conditioned medium alone or plus MDP. Anti
      IFN-gamma mAb completely abrogated MGC generation, whereas anti-GM-CSF and anti
      IL-3 mAbs significantly inhibited LGCs. These findings suggest that
      CD14(++)/CD16(-) monocytes are fused to form LGCs by MDP derived from
      granulomatous-disease-causing pathogens with inflammatory mediators such as IFN
      gamma, IL-3, and GM-CSF.

PMID- 11527989
TI  - Agonist-dependent failure of neutrophil function in diabetes correlates with
      extent of hyperglycemia.
AB  - Inexplicable controversies with regard to possible functional defects of
      neutrophilic polymorphonuclear leukocytes (PMNs) in diabetes persist. The purpose
      of the present study was to elucidate the relative effectiveness of several PMN
      agonists in stimulating lysosomal-enzyme secretion and leukotriene (LT) B(4)
      production by PMNs isolated from diabetic subjects. Formyl-methionyl-leucyl
      phenylalanine (fMLP) and platelet-activating factor (PAF) induced significantly
      less lysosomal-enzyme secretion and LTB(4) production in diabetic-subject PMNs
      than in normal-subject PMNs. It is surprising that PMNs from these same diabetic
      subjects responded normally after stimulation with A23187, serum-opsonized
      zymosan, or phorbol myristate acetate. The in vitro responsiveness of PMNs
      stimulated with fMLP or PAF was inversely correlated with indices of in vivo
      glycemic control (fasting plasma glucose and glycated-hemoglobin levels). In
      combination, these results indicate that hyperglycemia is associated with
      sustained decreases in PMN function but only in response to agonists that
      initiate stimulus-response coupling via G-protein-coupled receptors. This agonist
      selective reduction in PMN responsiveness may contribute to the compromised host
      defense associated with sustained hyperglycemia in diabetes.

PMID- 11527990
TI  - Different orders for acquisition of apoptotic characteristics by leukocytes.
AB  - Apoptotic leukocytes undergo cellular changes that are used as markers for
      "early" versus "late" stages of apoptosis. To ascertain if the order for
      acquisition of these changes is unique to specific hematopoietic cell types, we
      compared four leukocyte cell types and the following five apoptotic
      characteristics: MC540 incorporation, annexin V-FITC binding, propidium iodide
      (PI) labeling of hypodiploid nuclei, DNA fragmentation by a colorimetric assay,
      and cell membrane permeability to PI. The order for acquisition of these
      apoptotic characteristics was significantly different for each of the leukocyte
      cell types and for the mode of induction of apoptosis. It is interesting that the
      nuclear changes but not the membrane changes studied in mouse spleen cells
      required caspase activity. In summary, the acquisition of these apoptotic
      characteristics occurs through caspase-dependent and caspase-independent
      mechanisms, and importantly, the order for acquisition of the characteristics is
      specific for the cell type and for the mode of induction of apoptosis.

PMID- 11527991
TI  - Induction of fibroblast-like cells from CD34(+) progenitor cells of the bone
      marrow in rheumatoid arthritis.
AB  - To assess the role of bone marrow in the pathogenesis of rheumatoid arthritis
      (RA), we examined the capacity of CD34(+) cells from bone marrow to generate
      fibroblast-like type B synoviocytes. CD34(+) cells from the bone marrow of 22 RA
      patients differentiated into cells with fibroblast-like morphology, which
      expressed prolyl 4-hydroxylase, in the presence of stem cell factor (SCF),
      granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis
      factor alpha (TNF-alpha), much more effectively than CD34(+) cells from bone
      marrow of 15 control subjects (10 patients with osteoarthritis and 5 healthy
      individuals). The generation of fibroblast-like cells was not at all observed in
      cultures with SCF, GM-CSF, and interleukin 4 (IL-4) with or without TNF-alpha.
      Generation of fibroblast-like cells was correlated with matrix metalloproteinase
      (MMP)-1 levels in culture supernatants. Thus, MMP-1 levels were significantly
      higher in TNF-alpha-stimulated cultures of bone marrow CD34(+) cells from
      patients with RA than in those from the control group. These results indicate
      that bone marrow CD34(+) cells from patients with RA have abnormal capacities to
      respond to TNF-alpha and to differentiate into fibroblast-like cells producing
      MMP-1, suggesting that bone marrow CD34(+) progenitor cells might generate type B
      synoviocytes and thus could play an important role in the pathogenesis of RA.

PMID- 11527993
TI  - CXCR4 undergoes complex lineage and inducing agent-dependent dissociation of
      expression and functional responsiveness to SDF-1alpha during myeloid
      differentiation.
AB  - The CXC chemokine SDF-1 and its receptor CXCR4 mediate myelopoiesis, presumably
      by regulating the homing of hematopoietic progenitor cells. We used the inducible
      HL-60 cell line as a model system for comparative analysis of CXCR4 expression
      during differential maturation into the granulocytic or monocytic phenotypes.
      Five different measures of CXCR4 expression and functional coupling: mRNA and
      surface expression, SDF-1-mediated [(35)S]GTPgammaS binding, calcium flux, and
      chemotaxis were examined simultaneously. Granulocytic differentiation with
      dimethyl sulfoxide induced surface expression of CXCR4 as well as SDF-1-mediated
      [(35)S]GTPgammaS binding and chemotaxis, whereas calcium flux was attenuated by
      twofold to threefold in HL-60 cells. Conversely, monocytic differentiation with
      vitamin D(3) inhibited surface expression and SDF-1-mediated chemotaxis, even as
      it induced [(35)S]GTPgammaS binding and calcium flux by more than twofold. Sodium
      butyrate up-regulated all parameters of CXCR4 expression studied. Together, these
      results demonstrate that CXCR4 expression undergoes complex regulation at
      multiple checkpoints, with the likely involvement of different G-proteins for
      signal transduction during cellular differentiation and following activation with
      SDF-1.

PMID- 11527992
TI  - IL-12 plays a pivotal role in LFA-1-mediated T cell adhesiveness by up-regulation
      of CCR5 expression.
AB  - The chemokine receptor CCR5 has been implicated in the recruitment of T cells to
      inflammatory sites. However, the regulation of CCR5 induction on T cells and its
      contribution to T cell adhesiveness are poorly understood. Using a Th1 clone,
      2D6, that can be maintained with interleukin (IL)-12 or IL-2 alone (designated
      2D6(IL-12) or 2D6(IL-2), respectively), we investigated how CCR5 is induced on T
      cells and whether CCR5 is responsible for up-regulating the function of adhesion
      molecules. 2D6(IL-12) grew, forming cell aggregates, in culture containing IL-12.
      This was due to lymphocyte function-associated antigen (LFA)-1-intercellular
      adhesion molecule (ICAM)-1 interaction, because 2D6(IL-12) expressed both LFA-1
      and ICAM-1 and cell aggregation was inhibited by anti-ICAM-1 monoclonal antibody.
      Despite comparable levels of LFA-1 and ICAM-1 expression, 2D6(IL-2) cells did not
      aggregate in culture with IL-2. It is important that there was a critical
      difference in CCR5 expression between 2D6(IL-12) and 2D6(IL-2); the former
      expressed high levels of CCR5, and the latter expressed only marginal levels.
      Both types of cells expressed detectable albeit low levels of RANTES (regulated
      on activation, normal T expressed and secreted) mRNA. Unlike IL-12 or IL-2, IL-18
      induced high levels of RANTES mRNA expression without modulating CCR5 expression.
      Therefore, combined stimulation with IL-12 and IL-18 strikingly up-regulated 2D6
      cell aggregation. Notably, LFA-1-mediated aggregation of 2D6(IL-12) cells was
      suppressed by anti-CCR5 antibody. These results indicate that IL-12 plays a
      critical role in CCR5 expression on Th1 cells and consequently contributes to
      CCR5-mediated activation of LFA-1 molecules.

PMID- 11527994
TI  - Interleukin-12 increases interleukin 8 production and release by human
      polymorphonuclear neutrophils.
AB  - Interleukin (IL) 12 is a heterodimeric cytokine mainly produced by phagocytes
      important target cells for IL-12 in particular with a chemotactic effect-and
      antigen-presenting cells in response to various microorganisms. Because IL-8 is a
      strong chemokine for polymorphonuclear neutrophils (PMNs), we investigated the
      effect of IL-12 on PMN IL-8 production. IL-12 alone had no significant effect,
      but with lipopolysaccharide (LPS) it was additive at both protein and mRNA
      levels. Actinomycin D at the beginning of culture inhibited IL-8 mRNA induction,
      whereas late addition affected IL-8 transcript stability, suggesting gene
      transcription involvement. Results with parthenolide and tyrphostin AG490 suggest
      that nuclear factor-kappaB and signal transducer and activator of transcription 4
      play a role. The IL-12 additive effect was restricted to IL-8 release, with no
      action on cell-associated IL-8. IL-12 additive effects occurred after 18 h of
      culture, with no marked up-regulation of IL-12 receptor expression, and were
      blocked by actinomycin D added after 16 h of culture. Tumor necrosis factor (TNF)
      alpha and interferon (IFN) gamma had intermediate roles; their specific
      inhibition reduced IL-12's effect. IL-12's chemotactic mechanism seemed mediated
      by overproduction and release of IL-8 by human PMNs in the presence of LPS, an
      effect involving TNF-alpha and IFN-gamma secretion. These results point to a new
      role for IL-12 in inflammation, through an autocrine amplification loop.

PMID- 11527995
TI  - Regulation of interleukin-8 gene expression after phagocytosis of zymosan by
      human monocytic cells.
AB  - Monocyte phagocytosis of pathogens or inflammatory debris leads to chemokine
      secretion and heralds the influx of leukocytes to the site of injury. Persistent
      chemokine secretion can lead to tissue damage. However, the mechanisms by which
      phagocytosis regulates chemokine synthesis remain poorly understood. As a first
      step, we have studied regulation of interleukin (IL) 8 gene expression after
      interaction with zymosan or latex. IL-8 secretion was consistently one- or
      twofold higher after incubation with zymosan than with latex. Nuclear factor (NF)
      kappaB translocation to the nucleus was induced by zymosan but not latex,
      indicating that its translocation is dependent on the nature of the phagocytic
      stimulus. NFkappaB activation coincided with IkappaBalpha degradation but had no
      effect on processing of NFkappaB1/p105, the precursor of the NFkappaB protein
      p50. The NFkappaB inhibitor gliotoxin abrogated zymosan-induced IL-8 synthesis in
      peripheral blood monocytes, further demonstrating that the induction of IL-8 mRNA
      by zymosan is NFkappaB dependent. SB203580 inhibition of the p38 mitogen
      activated protein kinase (MAPK) pathway significantly decreased zymosan-induced
      IL-8 mRNA accumulation. Inhibitors of protein kinases A and C or tyrosine kinases
      had no significant effect on zymosan-induced IL-8 synthesis. These data indicate
      that p38 MAPK and NFkappaB are critical in controlling zymosan-induced IL-8
      secretion.

PMID- 11527996
TI  - CCR1 chemokine receptor expression isolates erythroid from granulocyte-macrophage
      progenitors.
AB  - Simple methods that separate progenitor cells of different hemopoietic lineages
      would facilitate studies on lineage commitment and differentiation. We used an
      antibody specific for the chemokine receptor CCR1 to examine mononuclear cells
      isolated from cord blood samples. When CD34(+) cells were separated into
      CD34(+)CCR1(+) and CD34(+)CCR1(-) cells and plated in colony-forming assays, the
      granulocyte/macrophage progenitors were found almost exclusively in the
      CD34(+)CCR1(+) cells. In contrast, the CD34(+)CCR1(-) cells contained the
      majority of the erythroid progenitors. There was a highly significant difference
      (P<0.002) in the total percentage distribution of both granulocyte-macrophage
      colony-forming cells and erythroid burst-forming units between the two
      populations. This is the first report of separation of erythroid progenitors from
      granulocyte/macrophage progenitors using a chemokine receptor antibody in cord
      blood samples. These results suggest that at the clonogenic progenitor cell stage
      the expression of CCR1 might be lineage-specific. This method should prove useful
      for studies on erythroid progenitor and granulocyte/macrophage differentiation.

PMID- 11527997
TI  - Circular minidefensins and posttranslational generation of molecular diversity.
AB  - We purified two new minidefensins (RTD-2 and RTD-3) from the bone marrow of
      rhesus monkeys. Both were circular octadecapeptides that contained three
      intramolecular disulfide bonds and were homologous to RTD-1, a circular (theta)
      defensin previously described by Tang et al. (Science, 286, 498-502, 1999).
      However, whereas the 18 residues of RTD-1 represent spliced nonapeptide fragments
      derived from two different demidefensin precursors, RTD-2 and -3 comprise tandem
      nonapeptide repeats derived from only one of the RTD-1 precursors. Thus, circular
      minidefensins are products of a novel posttranslational system that generates
      effector molecule diversity without commensurate genome expansion. A system
      wherein two demidefensin genes can produce three circular minidefensins might
      allow n such genes to produce (n/2)(n+1) peptides.

PMID- 11527998
TI  - Chemokine/chemokine receptor nomenclature.

PMID- 11527999
TI  - Biological degradation of 2,4,6-trinitrotoluene.
AB  - Nitroaromatic compounds are xenobiotics that have found multiple applications in
      the synthesis of foams, pharmaceuticals, pesticides, and explosives. These
      compounds are toxic and recalcitrant and are degraded relatively slowly in the
      environment by microorganisms. 2,4,6-Trinitrotoluene (TNT) is the most widely
      used nitroaromatic compound. Certain strains of Pseudomonas and fungi can use TNT
      as a nitrogen source through the removal of nitrogen as nitrite from TNT under
      aerobic conditions and the further reduction of the released nitrite to ammonium,
      which is incorporated into carbon skeletons. Phanerochaete chrysosporium and
      other fungi mineralize TNT under ligninolytic conditions by converting it into
      reduced TNT intermediates, which are excreted to the external milieu, where they
      are substrates for ligninolytic enzymes. Most if not all aerobic microorganisms
      reduce TNT to the corresponding amino derivatives via the formation of nitroso
      and hydroxylamine intermediates. Condensation of the latter compounds yields
      highly recalcitrant azoxytetranitrotoluenes. Anaerobic microorganisms can also
      degrade TNT through different pathways. One pathway, found in Desulfovibrio and
      Clostridium, involves reduction of TNT to triaminotoluene; subsequent steps are
      still not known. Some Clostridium species may reduce TNT to
      hydroxylaminodinitrotoluenes, which are then further metabolized. Another pathway
      has been described in Pseudomonas sp. strain JLR11 and involves nitrite release
      and further reduction to ammonium, with almost 85% of the N-TNT incorporated as
      organic N in the cells. It was recently reported that in this strain TNT can
      serve as a final electron acceptor in respiratory chains and that the reduction
      of TNT is coupled to ATP synthesis. In this review we also discuss a number of
      biotechnological applications of bacteria and fungi, including slurry reactors,
      composting, and land farming, to remove TNT from polluted soils. These treatments
      have been designed to achieve mineralization or reduction of TNT and
      immobilization of its amino derivatives on humic material. These approaches are
      highly efficient in removing TNT, and increasing amounts of research into the
      potential usefulness of phytoremediation, rhizophytoremediation, and transgenic
      plants with bacterial genes for TNT removal are being done.

PMID- 11528002
TI  - Questionable thymic nurse cell.
AB  - Since their discovery in 1980, thymic nurse cells (TNCs) have been controversial.
      Questions pertaining to the existence of the TNC as a "unit" cell with thymocytes
      completely enclosed within its cytoplasm were the focus of initial debates. Early
      skeptics proposed the multicellular complex to be an artifact of the procedures
      used to isolate TNCs from the thymus. Since that time, TNCs have been found in
      fish, frogs, tadpoles, chickens, sheep, pigs, rats, mice, and humans. Their
      evolutionary conservation throughout the animal kingdom relieved most
      speculations about the existence of TNCs and at the same time demonstrated their
      apparent importance to the thymus and T-cell development. In this review we will
      discuss and debate reports that describe (i) the organization or structure of
      TNCs, (ii) the thymocyte subset(s) found within the cytoplasm of TNCs and their
      uptake and release, and (iii) the function of this fascinating multicellular
      interaction that occurs during the process of T-cell development. Discussions
      about the future of the field and experimental approaches that will lead to
      answers to remaining questions are also presented.

PMID- 11528000
TI  - Sodium ion cycle in bacterial pathogens: evidence from cross-genome comparisons.
AB  - Analysis of the bacterial genome sequences shows that many human and animal
      pathogens encode primary membrane Na+ pumps, Na+-transporting dicarboxylate
      decarboxylases or Na+ translocating NADH:ubiquinone oxidoreductase, and a number
      of Na+ -dependent permeases. This indicates that these bacteria can utilize Na+
      as a coupling ion instead of or in addition to the H+ cycle. This capability to
      use a Na+ cycle might be an important virulence factor for such pathogens as
      Vibrio cholerae, Neisseria meningitidis, Salmonella enterica serovar Typhi, and
      Yersinia pestis. In Treponema pallidum, Chlamydia trachomatis, and Chlamydia
      pneumoniae, the Na+ gradient may well be the only energy source for secondary
      transport. A survey of preliminary genome sequences of Porphyromonas gingivalis,
      Actinobacillus actinomycetemcomitans, and Treponema denticola indicates that
      these oral pathogens also rely on the Na+ cycle for at least part of their energy
      metabolism. The possible roles of the Na+ cycling in the energy metabolism and
      pathogenicity of these organisms are reviewed. The recent discovery of an
      effective natural antibiotic, korormicin, targeted against the Na+ -translocating
      NADH:ubiquinone oxidoreductase, suggests a potential use of Na+ pumps as drug
      targets and/or vaccine candidates. The antimicrobial potential of other
      inhibitors of the Na+ cycle, such as monensin, Li+ and Ag+ ions, and amiloride
      derivatives, is discussed.

PMID- 11528003
TI  - Allosteric regulation of catalytic activity: Escherichia coli aspartate
      transcarbamoylase versus yeast chorismate mutase.
AB  - Allosteric regulation of key metabolic enzymes is a fascinating field to study
      the structure-function relationship of induced conformational changes of
      proteins. In this review we compare the principles of allosteric transitions of
      the complex classical model aspartate transcarbamoylase (ATCase) from Escherichia
      coli, consisting of 12 polypeptides, and the less complicated chorismate mutase
      derived from baker's yeast, which functions as a homodimer. Chorismate mutase
      presumably represents the minimal oligomerization state of a cooperative enzyme
      which still can be either activated or inhibited by different heterotropic
      effectors. Detailed knowledge of the number of possible quaternary states and a
      description of molecular triggers for conformational changes of model enzymes
      such as ATCase and chorismate mutase shed more and more light on allostery as an
      important regulatory mechanism of any living cell. The comparison of wild-type
      and engineered mutant enzymes reveals that current textbook models for regulation
      do not cover the entire picture needed to describe the function of these enzymes
      in detail.

PMID- 11528001
TI  - Receptors and entry cofactors for retroviruses include single and multiple
      transmembrane-spanning proteins as well as newly described
      glycophosphatidylinositol-anchored and secreted proteins.
AB  - In the past few years, many retrovirus receptors, coreceptors, and cofactors have
      been identified. These molecules are important for some aspects of viral entry,
      although in some cases it remains to be determined whether they are required for
      binding or postbinding stages in entry, such as fusion. There are certain common
      features to the molecules that many retroviruses use to gain entry into the cell.
      For example, the receptors for most mammalian oncoretroviruses are multiple
      membrane-spanning transport proteins. However, avian retroviruses use single-pass
      membrane proteins, and a sheep retrovirus uses a glycosylphosphatidylinositol
      anchored molecule as its receptor. For some retroviruses, particularly the
      lentiviruses, two cell surface molecules are required for efficient entry. More
      recently, a soluble protein that is required for viral entry has been identified
      for a feline oncoretrovirus. In this review, we will focus on the various
      strategies used by mammalian retroviruses to gain entry into the cell. The choice
      of receptors will also be discussed in light of pressures that drive viral
      evolution and persistence.

PMID- 11528007
TI  - Liver disorder and the HFE locus.

PMID- 11528004
TI  - Metabolic context and possible physiological themes of sigma(54)-dependent genes
      in Escherichia coli.
AB  - Sigma(54) has several features that distinguish it from other sigma factors in
      Escherichia coli: it is not homologous to other sigma subunits, sigma(54)
      dependent expression absolutely requires an activator, and the activator binding
      sites can be far from the transcription start site. A rationale for these
      properties has not been readily apparent, in part because of an inability to
      assign a common physiological function for sigma(54)-dependent genes. Surveys of
      sigma(54)-dependent genes from a variety of organisms suggest that the products
      of these genes are often involved in nitrogen assimilation; however, many are
      not. Such broad surveys inevitably remove the sigma(54)-dependent genes from a
      potentially coherent metabolic context. To address this concern, we consider the
      function and metabolic context of sigma(54)-dependent genes primarily from a
      single organism, Escherichia coli, in which a reasonably complete list of
      sigma(54)-dependent genes has been identified by computer analysis combined with
      a DNA microarray analysis of nitrogen limitation-induced genes. E. coli appears
      to have approximately 30 sigma(54)-dependent operons, and about half are involved
      in nitrogen assimilation and metabolism. A possible physiological relationship
      between sigma(54)-dependent genes may be based on the fact that nitrogen
      assimilation consumes energy and intermediates of central metabolism. The
      products of the sigma(54)-dependent genes that are not involved in nitrogen
      metabolism may prevent depletion of metabolites and energy resources in certain
      environments or partially neutralize adverse conditions. Such a relationship may
      limit the number of physiological themes of sigma(54)-dependent genes within a
      single organism and may partially account for the unique features of sigma(54)
      and sigma(54)-dependent gene expression.

PMID- 11528008
TI  - Cholesterol lowering in the older population: time for reassessment?
AB  - Hypercholesterolaemia is an established major risk factor for coronary heart
      disease (CHD) in the general population. In the vast majority of studies that
      focused on this particular age group and carefully eliminated other confounding
      factors such as co-morbid conditions, hypercholesterolaemia was a risk factor for
      CHD in the older population. Because the prevalence of CHD increases with
      advancing age, studies that consider not only the relative risk attributed to
      cholesterol but also the absolute numbers of people affected, show
      hypercholesterolaemia to be an even stronger risk factor in the elderly. Large
      primary and secondary prevention studies of HMG-CoA reductase inhibitors
      (statins) in the elderly have shown a reduction in major coronary events similar
      to that observed in the younger age group. The role of hypercholesterolaemia as a
      risk factor for stroke is less clear, and a major limitation is the heterogeneous
      nature of the disease. Nevertheless, most studies that evaluated non-haemorrhagic
      strokes separately showed a positive association with cholesterol levels, and
      statin therapy is effective in preventing stroke. These data provide a rationale
      for treating older hypercholesterolaemic people with statins, not only to prevent
      CHD, but also to prevent stroke.

PMID- 11528006
TI  - Autophagy in yeast: mechanistic insights and physiological function.
AB  - Unicellular eukaryotic organisms must be capable of rapid adaptation to changing
      environments. While such changes do not normally occur in the tissues of
      multicellular organisms, developmental and pathological changes in the
      environment of cells often require adaptation mechanisms not dissimilar from
      those found in simpler cells. Autophagy is a catabolic membrane-trafficking
      phenomenon that occurs in response to dramatic changes in the nutrients available
      to yeast cells, for example during starvation or after challenge with rapamycin,
      a macrolide antibiotic whose effects mimic starvation. Autophagy also occurs in
      animal cells that are serum starved or challenged with specific hormonal stimuli.
      In macroautophagy, the form of autophagy commonly observed, cytoplasmic material
      is sequestered in double-membrane vesicles called autophagosomes and is then
      delivered to a lytic compartment such as the yeast vacuole or mammalian lysosome.
      In this fashion, autophagy allows the degradation and recycling of a wide
      spectrum of biological macromolecules. While autophagy is induced only under
      specific conditions, salient mechanistic aspects of autophagy are functional in a
      constitutive fashion. In Saccharomyces cerevisiae, induction of autophagy
      subverts a constitutive membrane-trafficking mechanism called the cytoplasm-to
      vacuole targeting pathway from a specific mode, in which it carries the resident
      vacuolar hydrolase, aminopeptidase I, to a nonspecific bulk mode in which
      significant amounts of cytoplasmic material are also sequestered and recycled in
      the vacuole. The general aim of this review is to focus on insights gained into
      the mechanism of autophagy in yeast and also to review our understanding of the
      physiological significance of autophagy in both yeast and higher organisms.

PMID- 11528009
TI  - A case ascertainment study of septic discitis: clinical, microbiological and
      radiological features.
AB  - We studied the spectrum of septic discitis presenting to two busy district
      general hospitals over 2.5 years (November 1996 to April 1999), surveying the
      case notes of all patients attending Royal Bournemouth and Poole Hospitals with
      probable septic discitis on magnetic resonance imaging (MRI). Twenty-two cases of
      septic discitis were identified, suggesting an annual incidence of 2/100
      000/year. Seventy-three percent of patients were aged > or =65 years. In 91% of
      patients, back pain was the presenting symptom, with neurological signs evident
      in 45% of patients. Fever >37.5 degrees C was present in 68% of patients, and a
      marked elevation of erythrocyte sedimentation rate (ESR) in 91%. Diagnosis was
      originally by MRI in 86% of patients, with plain radiographs not diagnostic of
      discitis in the early stages of the infection. Staphylococcus aureus was the
      commonest pathogen (41%), but in 18% of patients, no organism was identified. The
      major predisposing factors to septic discitis were invasive procedures (41%),
      underlying cancer (25%) and diabetes (18%). Pre-existing degenerative spinal
      disease was found in 50% of patients. Four patients whose causative organism was
      not isolated had a poorer outcome: one death and three with increased morbidity.
      Our estimated incidence rate (2/100 000/year) is higher than that in previous
      studies and may be due to a higher detection rate with MRI and/or a genuine
      increase in the number of cases. Septic discitis should be considered in any
      patient who has severe localized pain at any spinal level, especially if
      accompanied by fever and elevated ESR, or in the immunosuppressed.

PMID- 11528010
TI  - Abnormal serum free thyroid hormone levels due to heparin administration.
AB  - Fractionated or unfractionated heparin may produce artefactual elevation in
      measured concentrations of free thyroid hormones. Although the specific cause is
      unknown, it may be a consequence of displacement of thyroid hormones from their
      binding sites by free fatty acids liberated in vitro. We describe four cases of
      heparin-induced abnormalities in free thyroid hormone measurements where some
      diagnostic confusion was generated. Increasing physician awareness of this poorly
      appreciated entity may avert diagnostic confusion and unnecessary investigation.

PMID- 11528005
TI  - Polar flagellar motility of the Vibrionaceae.
AB  - Polar flagella of Vibrio species can rotate at speeds as high as 100,000 rpm and
      effectively propel the bacteria in liquid as fast as 60 microm/s. The sodium
      motive force powers rotation of the filament, which acts as a propeller. The
      filament is complex, composed of multiple subunits, and sheathed by an extension
      of the cell outer membrane. The regulatory circuitry controlling expression of
      the polar flagellar genes of members of the Vibrionaceae is different from the
      peritrichous system of enteric bacteria or the polar system of Caulobacter
      crescentus. The scheme of gene control is also pertinent to other members of the
      gamma purple bacteria, in particular to Pseudomonas species. This review uses the
      framework of the polar flagellar system of Vibrio parahaemolyticus to provide a
      synthesis of what is known about polar motility systems of the Vibrionaceae. In
      addition to its propulsive role, the single polar flagellum of V.
      parahaemolyticus is believed to act as a tactile sensor controlling surface
      induced gene expression. Under conditions that impede rotation of the polar
      flagellum, an alternate, lateral flagellar motility system is induced that
      enables movement through viscous environments and over surfaces. Although the
      dual flagellar systems possess no shared structural components and although
      distinct type III secretion systems direct the simultaneous placement and
      assembly of polar and lateral organelles, movement is coordinated by shared
      chemotaxis machinery.

PMID- 11528011
TI  - The anti-inflammatory effects of circulating fatty acids in obstructive jaundice:
      similarities with pregnancy-induced immunosuppression.
AB  - Rheumatoid arthritis (RA) is ameliorated during both obstructive jaundice and
      pregnancy. Previous studies of polymorphonuclear leukocyte (PMN) function during
      pregnancy have shown reductions in the stimulated release of arachidonic acid
      (AA) and leukotriene B4 (LTB4), and lower NADPH oxidase activity. These changes
      may account for the amelioration of RA. The cause of this reduction in PMN
      function appears to be a progressive change in circulating fatty acids (FA), with
      a reduction in polyunsaturated FA, predominantly AA. The NADPH oxidase
      responsible for the respiratory burst has a direct requirement for
      polyunsaturated FA, particularly AA. We investigated whether the same changes in
      PMN function and FA, occur during obstructive jaundice. Patients with biliary
      obstructions were investigated before and after surgical correction (n=14).
      Obstructive jaundice caused significant changes in the proportions of serum and
      cellular FA. There was a striking reduction in polyunsaturated FA, particularly
      AA (48% in serum, p<0.001; 42% in PMNs, p<0.001) and an increase in mono
      unsaturated oleic acid (24% in serum, p<0.001; 15% in PMNs, p<0.005). Similar
      changes occurred in mononuclear cell FA. Jaundice also caused a significant
      reduction in PMN function. Respiratory burst activity was reduced by between 32%
      and 38% in response to physiological and non-physiological stimuli, and there
      were similar significant reductions in the release of AA and LTB4. These changes
      in stimulated PMN function were evident whether or not the cells were first
      primed with tumour necrosis factor alpha (TNFalpha). Incubation of PMNs from
      healthy donors in pooled serum from patients with obstructive jaundice caused a
      reduction of 32% in cellular AA and 38% in NADPH oxidase activity. These findings
      support the idea that circulating FA can regulate PMN inflammatory
      responsiveness. The FA-induced attenuation in PMN activity in both jaundice and
      pregnancy may explain their ameliorating effects upon RA.

PMID- 11528012
TI  - Increased oxidative stress in Alzheimer's disease as assessed with 4
      hydroxynonenal but not malondialdehyde.
AB  - Oxidative stress is thought to play a major role in the pathogenesis of
      Alzheimer's disease (AD). Although there is strong post-mortem and experimental
      evidence of oxidative damage occurring in AD brains, the use of markers in the
      peripheral circulation to show oxidative stress is less convincing. We examined
      plasma from AD patients for markers of increased oxidative stress. We report
      elevated levels of 4-hydroxy-nonenal (4-HNE) in AD patients compared to controls
      (median 20.6, IQR 6.0-25.2 vs. 7.8, 3.3-14.5 micomol/l, respectively; p=0.001)
      but not malondialdehyde (MDA), and lower levels of ascorbate in AD plasma when
      compared to age-matched controls (9.9, 6.0-33.7 vs. 24.2, 13.9-48.6 micromol/l;
      p<0.05). Levels of 4-HNE in AD patients were inversely related to ascorbate (r=
      0.337; p=0.07) and Folstein Mini-Mental State Examination (MMSE) (r=-0.474;
      p=0.015). The concentration of protein sulphydryls, free-radical scavengers, was
      directly related to the MMSE result (r=0.427; p=0.03). Increased production of 4
      HNE indicates increased oxidative stress (lipid peroxidation), which is not
      evident using the more common marker MDA. This elevation of 4-HNE was related to
      the degree of cognitive impairment (MMSE).

PMID- 11528013
TI  - Venous serum chloride and bicarbonate measurements in the evaluation of
      respiratory function in motor neuron disease.
AB  - Respiratory failure, with or without pneumonia, is the usual cause of death in
      patients with motor neuron disease (MND). Forced vital capacity (FVC) is often
      used to monitor respiratory function in MND and is, in part, predictive of
      survival time. However, such volitional tests are unreliable in many patients,
      especially later in the disease, and access to hospital laboratories can also be
      a problem for some disabled patients. We assessed the use of domiciliary venous
      serum chloride and bicarbonate measurements in evaluating respiratory function in
      MND. Newly-diagnosed MND patients (n=23) were followed-up at home every 3 months
      for up to 15 months. Respiratory symptoms were measured using a questionnaire,
      and FVC was documented. Venous serum chloride and bicarbonate were also measured.
      One patient had symptoms of airway obstruction disease, and was excluded from the
      analysis. Ten patients developed abnormally low chloride (mean 95, range 88-97,
      reference interval 98-107 mmol/l) and an abnormally high bicarbonate (mean 33,
      range 31-37, reference interval 22-30 mmol/l) during follow-up, of whom eight
      died within the next 5 (mean 2.2, range 0.5-5) months; two were still alive at
      the end of the study but had developed respiratory symptoms. Twelve patients had
      normal chloride and bicarbonate during follow-up: all were still alive at 15
      months, all had a FVC of >50% predicted, and only one had respiratory symptoms at
      their last assessment. Raised bicarbonate and low chloride were associated with
      the presence of respiratory symptoms suggesting respiratory muscle weakness.
      Venous serum chloride and bicarbonate potentially can provide useful information
      about respiratory status and prognosis in MND patients.

PMID- 11528015
TI  - Acute myocardial infarction soon after nicotine replacement therapy.

PMID- 11528014
TI  - Respiratory muscle assessment in motor neurone disease.

PMID- 11528016
TI  - Antiphospholipid syndrome presenting as cardiac failure.

PMID- 11528017
TI  - Ethical Aspects of Animal to Human Xenografts.

PMID- 11528018
TI  - Xenotransplantation: A Historical Perspective.

PMID- 11528019
TI  - The Application of Xenotransplantation in Humans--Reasons to Delay.

PMID- 11528021
TI  - Xenotransplantation: The Need, The Immunologic Hurdles, and The Prospects for
      Success.

PMID- 11528020
TI  - The Imunologic Response to Xenografts.

PMID- 11528022
TI  - Xenotransplantation and Infectious Diseases.

PMID- 11528023
TI  - Xenograft Transplantation of the Infectious Disease Conundrum.

PMID- 11528024
TI  - Laboratory Animal Care Policies and Regulations: Canada.

PMID- 11528026
TI  - Laboratory Animal Care Policies and Regulations: New Zealand.

PMID- 11528025
TI  - Laboratory Animal Care Policies and Regulations: Japan.

PMID- 11528027
TI  - Laboratory Animal Care Policies and Regulations: United Kingdom.

PMID- 11528028
TI  - > Laboratory Animal Care Policies and Regulations: United States.

PMID- 11528029
TI  - Emerging Issues: The Impact of International Free Trade Agreements on Animal
      Research.

PMID- 11528030
TI  - Review of Polyclonal Antibody Production Procedures in Mammals and Poultry.

PMID- 11528031
TI  - Review of Selected Adjuvants Used in Antibody Production.

PMID- 11528032
TI  - Monoclonal Antibodies by Somatic Cell Fusion.

PMID- 11528033
TI  - Recombinant Antibody Technolgy.

PMID- 11528034
TI  - Institutional Policies and Guidelines on Adjuvants and Antibody Production.

PMID- 11528035
TI  - Guidelines for the Care and Use of Fish in Research.

PMID- 11528036
TI  - Amphibians as Laboratory Animals.

PMID- 11528037
TI  - Nonavian Reptiles as Laboratory Animals.

PMID- 11528038
TI  - Evaluation of Hypothermia for Anesthesia in Reptiles and Amphibians.

PMID- 11528039
TI  - Use of Electronic Communications for IACUC Functions.

PMID- 11528040
TI  - Future Costs of Chimpanzees in U.S. Research Institutions.

PMID- 11528041
TI  - The Laboratory Opossum (Monodelphis Domestica) in Laboratory Research.

PMID- 11528042
TI  - Unusual Laboratory Rodent Species: Research Uses, Care, and Associated
      Biohazards.

PMID- 11528044
TI  - The SPF Pig in Research.

PMID- 11528043
TI  - Establishing Specific Pathogen-Free (SPF) Nonhuman Primate Colonies.

PMID- 11528045
TI  - Transgenic Technology and Laboratory Animal Science.

PMID- 11528046
TI  - Special Report: The 1996 Guide for the Care and Use of Laboratory Animals.

PMID- 11528047
TI  - Using Computer Simulation Models of Physiological and Metabolic Processes in
      Laboratory Animals.

PMID- 11528048
TI  - Genetic and Demographic Modeling for Animal Colony and Population Management.

PMID- 11528049
TI  - Statistical Modeling Approaches to Genetic Analysis.

PMID- 11528050
TI  - Educational Simulation Models in the Biomedical Sciences.

PMID- 11528051
TI  - Current Inbred and Hybrid Rat and Mouse Models for Gereontological Research.

PMID- 11528052
TI  - Senescence-accelerated Mouse (SAM): With Special Reference to Development and
      Pathological Phenotypes.

PMID- 11528053
TI  - Heterogeneous Reference Populations in Animal Model Research in Aging.

PMID- 11528055
TI  - Birds as Models of Aging in Biomedical Research.

PMID- 11528054
TI  - Use of Transgenic Mice in Aging Research.

PMID- 11528057
TI  - Introduction to the Internet and World Wide Web.

PMID- 11528056
TI  - Small Nonhuman Primates as Potential Models of Human Aging.

PMID- 11528058
TI  - Animal Resources on the Web.

PMID- 11528060
TI  - Automating the Institutional Animal Care and Use Committee.

PMID- 11528059
TI  - Internet Resources in Primatology.

PMID- 11528061
TI  - Social Experience and Immune System Measures in Laboratory-housed Macaques:
      Implications for Management and Research.

PMID- 11528062
TI  - Why It Is Important to Understand Animal Behavior.

PMID- 11528063
TI  - Psychoneuroimmunology.

PMID- 11528064
TI  - Background and Overview of Comparative Genomics.
AB  - Comparative genomics---the cross-referencing of information on genome
      organization between species---provides an additional dimension to the Human
      Genome Project and can derive much information from it for the benefit of animal
      health and animal breeding. Arrangements of genes and other DNA sequences may be
      determined by a variety of genetic and physical techniques, at resolutions from
      the gross cytological level to the level of the single base pair. Gross
      arrangements and rearrangements can also be charted by comparative chromosome
      painting. Genome organization may then be compared across mammal---and other
      vertebrate---species. Genetic mapping is well advanced in several livestock
      species as well as rodent model species, and outline maps are available for at
      least 30 mammal species in eight orders. At the time of this writing, maps are
      being rapidly constructed for chicken and fish species. Comparisons, even over
      vast evolutionary time scales, show that the mammal genome---indeed, the
      vertebrate genome---has been highly conserved. Thus, information about location
      and function of genes is directly transferable across species and should greatly
      accelerate the search for genes that specify inherited diseases in domestic
      mammals and humans as well as genes that specify economically important traits.

PMID- 11528065
TI  - Internet Comparative Mapping Resources.

PMID- 11528066
TI  - Comparative Mapping Using Chromosome Sorting and Painting.

PMID- 11528067
TI  - Comparative Chromosome Painting of Primate Genomes.

PMID- 11528068
TI  - Chromosome Painting in Marsupials.

PMID- 11528069
TI  - The Mouse Gene Map.

PMID- 11528070
TI  - The Rat Gene Map.

PMID- 11528071
TI  - The Vole Gene Map.

PMID- 11528072
TI  - Gene Maps of Nonhuman Primates.

PMID- 11528073
TI  - The Cattle Gene Map.

PMID- 11528074
TI  - The Sheep Gene Map.

PMID- 11528075
TI  - The Horse Gene Map.

PMID- 11528076
TI  - The Dog Gene Map.

PMID- 11528077
TI  - The Fox Gene Map.

PMID- 11528078
TI  - The American Mink Gene Map.

PMID- 11528080
TI  - Gene Maps of Marsupials.

PMID- 11528079
TI  - The Common Shrew Gene Map.

PMID- 11528081
TI  - Gene Maps of Monotremes (Mammalian Subclass Prototheria).

PMID- 11528082
TI  - The Chicken Gene Map.

PMID- 11528084
TI  - The Pufferfish Gene Map.

PMID- 11528083
TI  - The Linkage Map of Xiphophorus Fishes.

PMID- 11528085
TI  - Comparative Chromosome Painting (Enclosed poster).

PMID- 11528086
TI  - Comparative Genome Maps of Vertebrates (Enclosed poster).

PMID- 11528087
TI  - Risks of Infection among Laboratory Rats and Mice at Major Biomedical Research
      Institutions.

PMID- 11528088
TI  - Microbiological Assessment of Laboratory Rats and Mice.

PMID- 11528089
TI  - Current Strategies for Controlling/Eliminating Opportunistic Microorganisms.

PMID- 11528091
TI  - Future Directions in Rodent Pathogen Control.

PMID- 11528090
TI  - Reflections on Future Needs in Research with Animals.

PMID- 11528092
TI  - Opportunistic Infections in Research Rodents: The Challenges Are Great and the
      Hour is Late.

PMID- 11528093
TI  - Retinal abnormalities in newly diagnosed adult acute myeloid leukemia.
AB  - Retinal abnormalities (RA) are very frequently observed in adult patients with
      acute myeloid leukemia (AML), but the clinical significance of these findings has
      not been fully investigated. We examined the fundus oculi in a cohort of 122
      adult patients with AML at presentation and analyzed some clinical and biological
      features to assess whether there was any association with RA. For this purpose,
      we subdivided the patients into two groups according to the presence or absence
      of RA (groups 1 and 2, respectively). We considered current laboratory parameters
      such as white blood cell (WBC) count, hemoglobin (Hb), platelets and serum
      lactate dehydrogenase (LDH). Moreover, we subdivided the patients into two groups
      according to age <60 (group A) or > or =60 years (group B) to evaluate a possible
      association between RA and response to treatment and/or overall survival (OS). In
      our series, a higher median age and a lower Hb value were associated with group 1
      (p = 0.001 and p = 0.04, respectively); the median LDH value was 812 U/l (range
      224-5,551) and 607 (range 181-5,244) for groups 1 and 2, respectively (p = 0.02).
      There was no association between RA and karyotypic alterations. In terms of
      outcome, in group A (<60 years), 80% patients who achieved complete remission
      (CR) were in group 2 vs. 13% nonresponders (NR) (p < 0.0001). Median OS of group
      2 patients was 49.7 months compared with 7.2 months for those in group 1 (p =
      0.002). In group B, 58% patients who achieved CR were in group 1 vs. 15% NR (p <
      0.006). Median OS of patients in group 2 was 14.6 months compared with 2.9 months
      in group 1 (p = 0.02). Our data show that RA are significantly associated with
      some biological features and with shorter OS in AML patients and this parameter
      seems to be an effective clinical sign of poor prognosis in terms of CR.

PMID- 11528095
TI  - Influence of cytokines and autologous lymphokine-activated killer cells on
      leukemic bone marrow cells and colonies in AML.
AB  - We have already shown that cytokine cocktails (IL-1beta, IL-3, IL-6, SCF, GM-CSF)
      and/or lymphokine-activated killer (LAK) cells can reduce the amounts of clonal,
      CD34-positive mononuclear bone marrow cells (BM-MNC) in acute myeloid leukemia
      (AML). In addition, the influence of those cocktails and/or LAK cells on the
      clonogenic potential of AML BM-MNC was investigated. BM colonies cultured in agar
      during different stages of the disease were immunophenotyped in situ: 17 patients
      at diagnosis, 14 patients in complete remission, 8 patients at relapse, 8 healthy
      donors. A significant reduction in leukemic cells and colonies positive for CD34
      after in vitro culture of BM-MNC with cytokine cocktails was achieved with all
      samples obtained at diagnosis (n = 8, p < 0.01), in 6 of 8 cases in complete
      remission but only in 2 of 6 cases at relapse. Cytokine cocktails stimulated
      granulopoiesis as well as B and T lymphopoiesis. Colonies with leukemic phenotype
      could never be detected in healthy BM. A significant reduction in leukemic
      colonies was achieved by coculture of BM-MNC (uncultured or cytokine precultured)
      with autologous LAK cells in all 4 cases at diagnosis and in 1 case at relapse.
      An additive effect of in vitro cytokine preincubation of BM samples on the
      leukemia-reducing effect of LAK cells could be demonstrated in all samples
      studied (p < 0.001; diagnosis: n = 10, relapse: n = 3, complete remission: n =
      7). Patients had a better prognosis if CD34-positive colonies in AML could be
      reduced by cytokine incubation (p = 0.03) or coculture with autologous LAK cells
      in vitro (p = 0.04). Our data show that cytokines as well as LAK cells alone and
      in combination can reduce, however not eliminate clonogenic AML cells. Such
      mechanisms might be responsible for maintaining stable remissions in AML.

PMID- 11528094
TI  - Efficacy of intravenous immunoglobulin in the treatment of thrombotic
      thrombocytopaenic purpura. A study of 44 cases.
AB  - Thrombotic thrombocytopaenic purpura (TTP) is characterised by platelet
      aggregation in the capillaries, thrombocytopaenia and microangiopathic haemolytic
      anaemia that result in organ ischaemia, mainly of the CNS and kidneys. Since the
      institution of plasma exchange therapy no further treatments have been proved to
      improve the survival and the relapse rate of TTP patients. In this retrospective
      study, we evaluated the efficacy of normal human immunoglobulin treatment in 44
      patients suffering from TTP. Patients were divided into two groups that either
      did not receive (group A: 15 patients) or received (group B: 29 patients) 400
      mg/kg of human normal immunoglobulin intravenously (ivIgG) for 5 days. All
      patients received treatment with corticosteroids, anti-platelet agents and plasma
      exchange. The results clearly showed that there was no statistically significant
      difference between the two groups in either remission rate or time to relapse
      following remission. In conclusion, this study did not prove any beneficial
      effect of ivIgG in the treatment of TTP patients.

PMID- 11528096
TI  - Cytoreduction and stem cell mobilization with a regimen of paclitaxel, etoposide
      and cyclophosphamide followed by autologous transplantation using a preparative
      regimen of busulfan, etoposide and cyclophosphamide for patients with advanced
      lymphoma.
AB  - Forty-one patients with advanced Hodgkin's disease or intermediate or high-grade
      lymphoma, after having received standard salvage chemotherapy, were treated with
      a nonablative high-dose regimen of paclitaxel, etoposide and cyclophosphamide (D
      TEC) to optimally cytoreduce their disease and simultaneously mobilize peripheral
      blood stem cells. This regimen produced a response rate of 78% (35% complete and
      43.2% partial response) and mobilized sufficient peripheral blood stem cells in
      94% of the patients. Thirty-two of these patients then underwent autologous
      progenitor cell transplantation after ablative conditioning with busulfan,
      etoposide and cyclophosphamide. Actuarial overall survival at 61 months was 71.9%
      with an event-free survival (EFS) of 65.6%. Median EFS was 24.4 months. EFS of
      patients responsive to salvage chemotherapy was 75% at 61 months, compared to
      33.3% at 51.4 months in patients resistant to salvage chemotherapy. EFS of
      patients with disease sensitive to D-TEC was 75% at 61 months compared to 0% at
      13.1 months in patients resistant to D-TEC. In a multivariate analysis, the only
      significant parameter for transplant outcome was sensitivity to D-TEC (p =
      0.016), but not sensitivity to standard salvage chemotherapy. Aggressive
      cytoreduction may permit even those patients who are resistant to standard
      salvage chemotherapy to become successful transplant candidates.

PMID- 11528097
TI  - Direct-antiglobulin-test-negative immune haemolytic anaemia and thrombocytopenia
      in a patient with Hodgkin's disease.
AB  - A case of direct-antiglobulin-test (DAT)-negative auto-immune haemolytic anaemia
      (AIHA) and immune thrombocytopenia (ITP) associated with Hodgkin's disease (HD)
      is reported. A 52-year-old male was admitted with anaemia, thrombocytopenia, and
      lymphadenopathy. The patient was DAT negative, although he exhibited the clinical
      features of warm-type AIHA and elevated levels of red-blood-cell-associated IgG
      (RBC-IgG). The serum level of platelet-associated IgG (PA-IgG) was markedly
      increased. A biopsy specimen of the inguinal lymph nodes showed HD of mixed
      cellularity. Marked improvement of subjective symptoms, normalization of
      haematological values and a decrease in the level of both RBC- and PA-IgG were
      observed after the start of combination chemotherapy for HD. Although the
      association of HD, ITP, and/or AIHA has been infrequently reported, the
      measurement of RBC-IgG is recommended in cases of HD with anaemia even though DAT
      is negative, since HD is known to be associated with various protean
      immunological abnormalities.

PMID- 11528098
TI  - Primary hepatic Burkitt's lymphoma with chronic hepatitis C.
AB  - The liver is an uncommon primary site for malignant lymphoma, and primary hepatic
      lymphoma has been found to make up 0.4% of all extranodal lymphomas. We report a
      rare case of a 75-year-old Japanese male with primary hepatic Burkitt's lymphoma,
      according to both the revised European-American Lymphoma classification and the
      new World Health Organization classification. As not only histological findings
      but also immunological features are deemed essential in the diagnosis of
      Burkitt's lymphoma, the previous 7 cases of primary hepatic Burkitt's lymphoma
      were not fully evaluated, using these criteria. As far as we know, this is the
      first case of primary hepatic Burkitt's lymphoma with typical features on
      histological, immunological and cytogenetical analysis. He had a history of
      chronic hepatitis C over several decades with subsequent liver cirrhosis. From
      our review of the literature and our case, the relationship between hepatitis C
      virus infection and the development of primary hepatic Burkitt's lymphoma remains
      obscure.

PMID- 11528099
TI  - Ten-year survivor with multiple myeloma in first complete remission following
      treatment with conventional chemotherapy. Case report and a review of the
      literature.
AB  - A 62-year-old woman with multiple myeloma, who has been in complete remission
      (CR) for 10 years, is reported. The patient was treated with conventional
      chemotherapy, including nitrosourea derivatives. Five patients with myeloma,
      including the present case, who have survived for 10 years or more in CR and on
      whom detailed clinical descriptions were published, are reviewed. Their disease
      condition represented "a cure" or "a state extremely close to cure". The review
      indicates the following favorable prognostic factors common to these patients:
      age < or =65 years and a rapid response to treatment. Progressive bone
      destruction and/or lytic changes at disease onset is perhaps not a bad prognostic
      factor in myeloma patients with excellent outcome.

PMID- 11528100
TI  - Bone marrow histopathology predicting blast crisis in chronic myeloid leukemia.

PMID- 11528101
TI  - Low incidence of human herpesvirus 8 in bone marrow samples from Brazilian
      patients with multiple myeloma.

PMID- 11528102
TI  - Expression of CD157 and CD38 antigens on human myeloid leukaemia cells: a similar
      pattern of modulation with differentiating inducers.

PMID- 11528104
TI  - Proceedings of the 14th International Chromosome Conference. September 4-8, 2001,
      Wurzburg, Germany.

PMID- 11528103
TI  - Feasibility of antenatal screening of beta-thalassemia in Mumbai, India.

PMID- 11528106
TI  - Prostate cancer and the problem of genotype phenotype correlation.

PMID- 11528105
TI  - Re-defining the chromatin loop domain.
AB  - It is commonly accepted that the loop domain represents the basic structural unit
      of eukaryotic chromatin associated with DNA replication, gene expression and
      higher order packaging. However, molecular-cytological information defining the
      loop domain is lacking. There are gaps in our knowledge of the loop structure and
      how it regulates gene expression. The combination of new data/reagents from the
      Human Genome Project plus the use of novel molecular cytological technology will
      provide answers. Here we briefly review the status of chromatin loop research and
      pose questions that need to be addressed. New experimental systems are also
      presented to target some long-standing issues regarding the structure and
      function of the chromatin loop domain and its relationship with the nuclear
      matrix. This new knowledge will have a profound impact for modern genetics and
      molecular medicine.

PMID- 11528107
TI  - Unusual chromosomal mosaicism as a cause of mental retardation and congenital
      malformations in a familial reciprocal translocation carrier,
      t(17;22)(q24.2;q11.23).
AB  - Familial reciprocal translocations are generally without phenotypic effect,
      although there is some evidence for a small excess of mental retardation and
      congenital malformations (MR/CM) in children carrying familial reciprocal
      translocations. Possible mechanisms whereby such translocations could have a
      phenotypic effect include cryptic unbalanced rearrangements, uniparental disomy,
      and disruption of putative genes at the breakpoints, unmasking recessive alleles
      on the normal homologs. Mosaicism for a supernumerary derivative chromosome in a
      carrier of a familial reciprocal translocation has not yet been described. We
      report a boy presenting with MR/CM and a familial reciprocal translocation,
      t(17;22)(q24.2;q11.23), inherited from the mother. Cytogenetic analysis of
      peripheral blood lymphocytes showed a balanced karyotype in all 32 analyzed
      metaphase spreads. Molecular genetic analysis was consistent with biparental
      origin of the normal homologs. In metaphase spreads from skin fibroblasts a
      supernumerary chromosome was found in all 24 cells analyzed and could be
      identified as der(22)t(17;22)(q24.2;q11.23). Several possible segregation modes
      at meiosis I followed by meiosis II or postzygotic nondisjunction of the der(22)
      might have led to this unusual chromosomal mosaicism. We propose hidden mosaicism
      as a possible cause for MR/CM in patients who apparently carry a balanced
      familial reciprocal translocation.

PMID- 11528108
TI  - Prothymosin alpha, a mammalian c-myc-regulated acidic nuclear protein, provokes
      the decondensation of human chromosomes in vitro.
AB  - Prothymosin (ProT alpha) is an acidic nuclear protein, widely distributed in
      mammalian cells, whose expression is regulated by c-myc and linked to cell
      proliferation. ProT alpha interacts with histone H1 via its acidic domain, and
      its overexpression provokes the unfolding of chromatin fibers. Here we show that
      incubation of human native metaphase chromosomes with ProT alpha induces their
      extensive unravelling suggesting a function of this protein in chromosome
      decondensation.

PMID- 11528109
TI  - Alteration of chromosome numbers by generation of minichromosomes -- is there a
      lower limit of chromosome size for stable segregation?
AB  - Practical applications of minichromosomes, generated by de novo composition or by
      truncation of natural chromosomes, rely on stable transmission of these
      chromosomes. Functional centromeres, telomeres and replication origins are
      recognized as prerequisites for minichromosome stability. However, it is not yet
      clear whether, and if yes, to what degree the chromatin content has a qualitative
      or quantitative impact on stable chromosome transmission. A small translocation
      chromosome, which arose after X-irradiation of a reconstructed field bean
      karyotype, comprised approximately 5% of the haploid metaphase complement and was
      found to consist of three pieces of duplicated chromatin and a wild-type
      centromere. This chromosome was stably transmitted through all meristematic and
      pollen grain mitoses but was frequently lost during meiosis (66% loss in
      hemizygous and 33% in homozygous condition). This minichromosome was only a
      little smaller than stably segregating translocation chromosomes (comprising
      approximately 6% of the genome) of a euploid field bean karyotype. The
      duplications specific for this minichromosome did not influence meiotic
      segregation when associated with non-duplicated chromatin of other chromosomes.
      In comparison with minichromosomes of other species, the possibility of a lower
      size limit for a stable chromosome transmission must therefore be considered
      which might be based, for instance, on insufficient lateral support of
      centromeres or on insufficient bivalent stability due to the incapability of
      chiasma formation.

PMID- 11528110
TI  - Two supernumerary marker chromosomes, originating from chromosomes 6 and 11, in a
      child with developmental delay and craniofacial dysmorphism.
AB  - The interpretation of the significance of marker chromosomes, which can be
      encountered at prenatal diagnosis, is extremely problematic. Various factors
      contribute to the difficulty of clarifying the phenotypic risks of supernumerary
      marker chromosomes, including differences in the size, structure, and origin of
      marker chromosomes, as well as the occurrence of multiple marker chromosomes of
      different origin in the same proband. Research on marker chromosomes is currently
      in a data-accumulation phase. We report the presence of two marker chromosomes,
      originating from chromosomes 6 and 11, in a child with developmental delay and
      craniofacial dysmorphism and discuss the related literature.

PMID- 11528111
TI  - Comparative genomic hybridization based strategy for the analysis of different
      chromosome imbalances detected in conventional cytogenetic diagnostics.
AB  - Today, conventional cytogenetics (CC) is the main technique in routine genetic
      diagnostics for the analysis of genotype/phenotype correlations. Additionally,
      fluorescence in situ hybridization (FISH) has proven to be useful for the
      characterization of structural chromosome aberrations found in conventional
      cytogenetics. Comparative genomic hybridization (CGH) is a molecular cytogenetic
      FISH approach developed for the detection of genomic imbalances with cytogenetic
      resolution. CGH allows the genome-wide assessment of relative DNA copy number
      changes using extracted specimen DNA as a probe. We investigated the capacity of
      CGH in cases referred for conventional cytogenetic diagnostics for the detection
      of chromosome imbalances. Three different groups of conspicuous karyotypes after
      CC (intrachromosomal rearrangements, interchromosomal rearrangements, and
      additional marker chromosomes) in pre- and postnatal diagnostic cases were
      surveyed by CGH to characterize the underlying imbalances of chromosome segments.
      All together, we investigated more than 100 cases by CGH and validated the
      results with other molecular cytogenetic methods. Here we present eight of these
      cases in order to demonstrate our CGH based strategy to analyze chromosomal de
      novo rearrangements. CGH provided additional cytogenetic information to
      complement conventional cytogenetic investigations. Additionally, CGH refined the
      description of the aberrant chromosome segments allowing us to further
      characterize the underlying mechanisms involved.

PMID- 11528112
TI  - The combination of SKY and specific loci detection with FISH or immunostaining.
AB  - Spectral karyotyping (SKY) represents an effective tool to detect individual
      chromosomes and analyze major karyotype abnormalities within an entire genome. We
      have tested the feasibility of combining SKY and FISH/protein detection in order
      to combine SKY's unique abilities with specific loci detection. Our experimental
      results demonstrate that various combined protocols involving SKY, FISH and
      immunostaining work well when proper procedures are used. This combined approach
      allows the tracking of key genes or targeted chromosome regions while monitoring
      changes throughout the whole genome. It is particularly useful when
      simultaneously monitoring the behavior of both protein complexes and DNA loci
      within the genome. The details of this methodology are described and
      systematically tested in this communication.

PMID- 11528113
TI  - Telomere shortening in Fanconi anaemia demonstrated by a direct FISH approach.
AB  - Analysis of telomere status in patients with Fanconi anaemia (FA) has previously
      been carried out by measurement of telomere restriction fragment (TRF) length by
      Southern blotting and densitometry. Results from these studies indicated that FA
      patients had significant reduction in telomere length compared with age-matched
      controls. This paper confirms and extends these findings using a direct FISH
      technique, which showed that 15 out of 16 FA patients had increased loss of
      telomere signals compared with controls. In 12 out of the 16 patients, decrease
      in telomere signal intensity could also be detected using a Q-FISH approach.

PMID- 11528114
TI  - Meningioma: a cytogenetic model of a complex benign human tumor, including data
      on 394 karyotyped cases.
AB  - Meningioma is the most frequent tumor of neuroectodermal origin in humans. It is
      usually benign. Only a minority of cases shows progression to an anaplastic tumor
      (WHO grade II and III). Meningioma is generally a sporadic tumor. Multiple and
      familial cases are rare and mostly associated with (hereditary) neurofibromatosis
      2 (NF2). Meningiomas show an unexpectedly high recurrence rate. Also, completely
      removed low-grade tumors can recur. Recurrence and multiplicity are correlated
      with the formation of a peritumoral edema. On the cytogenetic level, meningioma
      is the best-studied tumor in humans. Grade I tumors show either uniform monosomy
      22 or a diploid karyotype. The majority of high-grade, but only a minority of low
      grade, meningiomas show loss of merlin, a cytoskeleton-cytoplasm-linker protein.
      Merlin is the product of the NF2 gene located on chromosome 22. A second tumor
      suppressor gene on chromosome 22 has not yet been detected. In contrast to other
      solid tumors, progression of meningiomas is correlated with increasing
      hypodiploidy, showing characteristic clonal evolutions that mostly include
      chromosomes 14, 18, and 19 and, more rarely, 6 and 10. Structural aberrations are
      infrequent, except for the loss of the short arm of chromosome 1, which appears
      to be the decisive step for anaplastic growth. Comparative histochemical and
      molecular cytogenetic studies point to the alkaline phosphatase gene (ALPL, liver
      bone-kidney type) located on 1p36.1-->p34 as a candidate tumor suppressor gene. A
      model is proposed that tries to explain - with a minimum number of essential
      steps - the origin, progression, infiltration, and recurrence of meningiomas.

PMID- 11528115
TI  - Genomic imbalances in 61 renal cancers from the proximal tubulus detected by
      comparative genomic hybridization.
AB  - Comparative genomic hybridization (CGH) has been applied to characterize 61
      primary renal cell carcinomas derived histogenetically from the proximal tubulus.
      The tumor samples comprised 46 clear-cell renal cell carcinomas (ccRCCs) and 15
      papillary renal cell carcinomas (pRCCs). Changes in the copy number of entire
      chromosomes or subregions were detected in 56 tumors (92%). In ccRCCs, losses of
      chromosome 3 or 3p (63%); 14q (30%); 9 (26%); 1 and 6 or 6q (17% each); 4 and 8
      or 8p (15% each); 22 (11%); 2 or 2q and 19 (9% each); 7q, 10, 16, 17p, 18, and Y
      (7% each); and 5, 11, 13, 15, and 21 (4% each) were detected. Most frequent
      genomic gains in ccRCC were found on chromosome 5 (63%); 7 (35%); 1 or 1q (33%);
      2q (24%); 8 or 8q, 12, and 20 (20% each); 3q (17%); 16 (15%); 19 (13%); 6 and 17
      or 17q (11% each); and 4, 10, 11, 21, and Y (9% each). In pRCCs, gains in the
      copy number of chromosomes 7 and 17 (7/15, each) and 16 and 20 (6/15, each) were
      frequent. One pRCC showed amplification of subchromosome regions 2q22-->q33, 16q,
      17q and the entire X chromosome. In pRCC, losses were less frequently seen than
      gains. Losses of chromosomes 1, 14, 15, and Y (3/15 each) and 2, 4, 6, and 13
      (2/15 each) were observed. In ccRCCs, statistical evaluation revealed significant
      correlations of chromosomal imbalances with tumor stage and grade, i.e., a gain
      in copy number of chromosome 5 correlated positively with low tumor grade,
      whereas a gain of chromosomes 10 and 17 correlated positively with high tumor
      grade. Furthermore, loss of chromosome 4 correlated positively with high tumor
      stage.

PMID- 11528116
TI  - Biased distribution of repetitive elements: a landmark for neo-Y chromosome
      evolution in Drosophila miranda.
AB  - It is generally assumed that the sex chromosomes developed from a pair of
      homologs. Over evolution, the proto-Y chromosome, with a very short differential
      segment, matured in its final stage into a heterochromatic and, for the most
      part, genetically eroded Y chromosome. The constraints on the evolution of the
      proto-Y chromosome have been speculated upon since the sex chromosomes were
      discovered. Several models have been suggested. Drosophila miranda has proved to
      be a unique and potent model system to study Y-chromosome evolution. We use
      selected test genes distributed along the neo-Y chromosome as entry gates to
      analyze the molecular mechanisms involved in the process of Y-chromosome
      evolution. Here, we report our findings on the Kruppel gene (Kr), which is
      located distally on the neo-sex chromosome pair.

PMID- 11528117
TI  - Genomic structure and chromosome location of the human gene encoding the zinc
      finger autoantigen ZNF330.
AB  - We have recently described a novel zinc finger cDNA, ZNF330, which was
      immunologically characterized as a new human autoantigen, highly conserved during
      evolution from nematodes to humans. The protein was found at the nucleolus and
      the cytoplasm in interphase and transiently associates with centromeres in
      mitosis as determined by immunofluorescence analysis. We now describe that the
      association of ZNF330 with the nucleolus but not with the cytoplasm is RNA
      dependent as shown by RNAse treatment of fixed culture cells, since ZNF330
      localization was unaffected by DNAse treatment. We also report the cloning,
      structural organization and chromosome location of the human ZNF330 gene. The
      gene is comprised of 10 exons and spans approximately 16 kb of genomic DNA. The
      conserved residues forming nine CXXC motifs are contained in exons 3 to 9.
      Several major transcription initiation sites were located 126, 124 and 121 bp
      upstream of the translation initiation codon ATG, as determined by primer
      extension analysis. The human ZNF330 gene was mapped by FISH to chromosome 4q31.1
      ->q31.2, the site of the FRA4C locus previously described as a common fragile
      site for acquired chromosome instability in humans.

PMID- 11528118
TI  - Genomic organization of the human NFAT5 gene: exon-intron structure of the 14-kb
      transcript and CpG-island analysis of the promoter region.
AB  - NFAT5, also known as tonicity enhancer binding protein (TonEBP) or NFATL1, is a
      new member of the immunologically important NFAT protein family. Despite its
      obvious relationship to this transcription factor family, NFAT5 shows distinct
      ways of regulation and function. The complete coding sequence and its alternative
      splice forms have been described previously. This sequence only refers to less
      than half of the total mRNA length. High conservation of this gene was shown
      among man, mouse, and pig. Here we report the cloning of the complete 14-kb cDNA
      sequence, its genomic organization, and a possible fourth isoform of the
      corresponding protein. Additionally, we describe the promoter region by CpG
      island methylation analysis.

PMID- 11528119
TI  - Reconstruction of the female Gorilla gorilla karyotype using 25-color FISH and
      multicolor banding (MCB).
AB  - The origin of the human and great ape chromosomes has been studied by comparative
      chromosome banding analysis and, more recently, by fluorescence in situ
      hybridization (FISH), using human whole-chromosome painting probes. It is not
      always possible, however, to determine the exact breakpoints and distribution or
      orientation of specific DNA regions using these techniques. To overcome this
      problem, the recently developed multicolor banding (MCB) probe set for all human
      chromosomes was applied in the present study to reanalyze the chromosomes of
      Gorilla gorilla (GGO). While the results agree with those of most previous
      banding and FISH studies, the breakpoints for the pericentric inversion on GGO 3
      were defined more precisely. Moreover, no paracentric inversion was found on GGO
      14, and no pericentric inversions could be demonstrated on GGO 16 or 17.

PMID- 11528120
TI  - Comparative cytogenetics of the African elephant (Loxodonta africana) and Asiatic
      elephant (Elephas maximus).
AB  - G- and C-banded karyotypes of the two extant species of the mammalian order
      Proboscidea are presented for the first time. Chromosome complements were 2n = 56
      in both Loxodonta africana and Elephas maximus. Comparisons between the species
      demonstrated a high level of chromosome band homology, with 26 conserved
      autosomal pairs. The normal diploid karyotype of L. africana had 25
      acrocentric/telocentric and two metacentric/submetacentric autosomal pairs. E.
      maximus differed by having one less acrocentric and one additional submetacentric
      pair due to either a heterochromatic arm addition or deletion involving autosomal
      pair 27. Several acrocentric autosomes of L. africana exhibited small short arms
      that were absent in homologous chromosomes of E. maximus. The X chromosomes in
      both species were large submetacentric elements and were homologous. However, the
      small acrocentric Y chromosomes differed; in E. maximus it was slightly larger
      and had more distinct G-bands than its counterpart in L. africana. Extant
      Elephantidae appear to be relatively conservative in their rates of chromosomal
      change compared to some other mammalian families. The high-quality banded
      karyotypes presented here should prove useful as references in future chromosome
      analyses of elephant populations and in comparative cytogenetic studies with
      other ungulate orders.

PMID- 11528121
TI  - Chromosomal evolution in the vlei rat, Otomys irroratus (Muridae: Otomyinae): a
      compound chromosomal rearrangement separates two major cytogenetic groups.
AB  - G- and C-banding delimits two cytogenetic groups within the vlei rat, Otomys
      irroratus. One has a diploid number of 2n = 24, resulting from a centric fusion
      of chromosomes 7 and 12 of the O. irroratus standard coupled with a tandem fusion
      to chromosome 8. The second has a diploid number of 2n = 28, lacks the compound
      chromosome, and appears to have a far wider geographic distribution within South
      Africa. Additionally, the two groups differ through the presence of cytotype
      specific heterozygous centric fusions and one to three B chromosomes which appear
      as floating polymorphisms in the 2n = 28 complex.

PMID- 11528122
TI  - Comparative FISH mapping of human cDNA clones to chromosomes of the musk shrew
      (Suncus murinus, Insectivora).
AB  - Forty-one cDNA clones of human functional genes were newly mapped to chromosomes
      of the musk shrew (Suncus murinus, Insectivora) by fluorescence in situ
      hybridization, and a comparative cytogenetic map of 51 genes, including 10 genes
      reported in our previous study, was constructed between human (HSA) and musk
      shrew (SMU) chromosomes. In this comparative map, the 51 genes localized to human
      autosomes, except HSA 8, 16, and 20, were mapped to 15 shrew autosomes, except
      SMU 4, 16, 17 and 18. Twelve conserved segments were identified between human and
      shrew chromosomes, and six segments among the musk shrew, human, and mouse. Our
      results defined the presence of at least one inversion and several
      interchromosomal rearrangements that occurred during evolution after the two
      species diverged from a common ancestor. Localization of three major
      histocompatibility complex (MHC) genes to shrew chromosome 3 suggested that the
      MHC genes of the musk shrew are located in a cluster on chromosome 3. The
      cytogenetic map constructed in this study is the first cytogenetic map with many
      functional genes in insectivore species. This approach provides clues for
      clarifying the chromosomal evolution in this order.

PMID- 11528123
TI  - The origin of four squirrel monkey cell lines established by karyotype analysis.
AB  - The squirrel monkey is a neotropical primate genus which is widely used in
      biomedical research but includes individual species and subspecies that respond
      differently to experimental perturbations. GTG-banding patterns of chromosomes 15
      and 16, which are distinct among different squirrel monkey species and
      subspecies, were used to determine the origin of three lung fibroblast cell lines
      from squirrel monkeys of unknown genetic background (DPSO 114/74, SqMkLu/68, and
      7603830) and to confirm the origin of a lymphoblast cell line (GSML) recently
      established from Guyanese squirrel monkey. DPSO 114/74 cells are from Peruvian
      squirrel monkey, SqMkLu/68 cells are Bolivian squirrel monkey, and 7603830 cells
      are from a Peruvian/Bolivian hybrid. Chromosome analysis of GSML cells confirmed
      that they are from Guyanese squirrel monkey.

PMID- 11528124
TI  - Chicken microchromosomes are hypermethylated and can be identified by specific
      painting probes.
AB  - Microdissection of single chicken microchromosomes (MICs) followed by degenerate
      oligonucleotide-primed (DOP) PCR allows the rapid generation of MIC-specific DNA
      libraries. Since some libraries derived from a single (or a few) chromosome(s)
      label the entire MIC fraction, the majority of chicken MICs share repetitive DNA
      sequences that are not found on the macrochromosomes. In evolutionarily distant
      bird species, MICs are invariably hypermethylated. Methylcytosine staining
      provides additional in situ evidence for the high gene content of MICs and strong
      compartmentalization of avian genomes.

PMID- 11528125
TI  - Ts65Dn -- localization of the translocation breakpoint and trisomic gene content
      in a mouse model for Down syndrome.
AB  - Fluorescent in situ hybridization (FISH) -- using mouse chromosome paints, probes
      for the mouse major centromeric satellite DNA, and probes for genes on
      chromosomes (Chr) 16 and 17 -- was employed to locate the breakpoint in a
      translocation used to produce a mouse model for Down syndrome. The Ts65Dn trisomy
      is derived from the reciprocal translocation T(16;17)65Dn. The Ts65Dn mouse
      carries a marker chromosome containing the distal segment of Chr 16, a region
      that shows linkage conservation with human Chr 21, and the proximal end of Chr
      17. This chromosome confers trisomy for most of the genes in the Chr 16 segment
      and Ts65Dn mice show many of the phenotypic features characteristic of Down
      syndrome. We used FISH on metaphase chromosomes from translocation T65Dn/+
      heterozygotes and Ts65Dn mice to show that the Chr 17 breakpoint is distal to the
      heterochromatin of Chr 17, that the Ts65Dn marker chromosome contains a small
      portion of Chr 17 euchromatin, that the Chr 16 breakpoint lies between the Ncam2
      and Gabpa/App genes, and that the Ts65Dn chromosome contains >80% of the human
      Chr 21 homologs. The significance of this finding is discussed in terms of the
      utility of this mouse model.

PMID- 11528126
TI  - Comparative architectural aspects of regions of conserved synteny on human
      chromosome 11p15.3 and mouse chromosome 7 (including genes WEE1 and LMO1).
AB  - Human chromosome 11p15.3 is associated with chromosome aberrations in the
      Beckwith Wiedemann Syndrome and implicated in the pathogenesis of different tumor
      types including lung cancer and leukemias. To date, only single tumor-relevant
      genes with linkage to this region (e.g. LMO1) have been found suggesting that
      this region may harbor additional potential disease associated genes. Although
      this genomic area has been studied for years, the exact order of genes/chromosome
      markers between D11S572 and the WEE1 gene locus remained unclear. Using the FISH
      technique and PAC clones of the flanking markers we determined the order of the
      genomic markers. Based on these clones we established a PAC contig of the
      respective region. To analyse the chromosome area in detail the synteny of the
      orthologous region on distal mouse chromosome 7 was determined and a
      corresponding mouse clone contig established, proving the conserved order of the
      genes and markers in both species: "cen-WEE1-D11S2043-ZNF143-RANBP7-CEGF1- ST5
      D11S932-LMO1-D11S572-TUB-tel", with inverted order of the murine genes with
      respect to the telomere/centromere orientation. The region covered by these
      contigs comprises roughly 1.6 MB in human as well as in mouse. The genomic
      sequence of the two subregions (around WEE1 and LMO1) in both species was
      determined using a shotgun sequencing strategy. Comparative sequence analysis
      techniques demonstrate that the content of repetitive elements seems to decline
      from centromere to telomere (52.6% to 34.5%) in human and in the corresponding
      murine region from telomere to centromere (41.87% to 27.82%). Genomic
      organisation of the regions around WEE1 and LMO1 was conserved, although the
      length of gene regions varied between the species in an unpredictable ratio. CpG
      islands were found conserved in putative promoter regions of the known genes but
      also in regions which so far have not been described as harboring expressed
      sequences.

PMID- 11528127
TI  - Comparative genomic sequencing reveals a strikingly similar architecture of a
      conserved syntenic region on human chromosome 11p15.3 (including gene ST5) and
      mouse chromosome 7.
AB  - Comparative genomics is a superior way to identify phylogenetically conserved
      features like genes or regions involved in gene regulation. The comparison of
      extended orthologous chromosomal regions should also reveal other characteristic
      traits essential for chromosome or gene function. In the present study we have
      sequenced and compared a region of conserved synteny from human chromosome
      11p15.3 and mouse chromosome 7. In human, this region is known to contain several
      genes involved in the development of various disorders like Beckwith-Wiedemann
      overgrowth syndrome and other tumor diseases. Furthermore, in the neighboring
      chromosome region 11p15.5 extensive imprinting of genes has been reported which
      might extend to region 11p15.3. The analysis of approximately 730 kb in human and
      620 kb in mouse led to the identification of eleven genes. All putative genes
      found in the mouse DNA were also present in the same order and orientation in the
      human chromosome. However, in the human DNA one putative gene of unknown function
      could be identified which is not present in the orthologous position of the mouse
      chromosome. The sequence similarity between human and mouse is higher in
      transcribed and exon regions than in non-transcribed segments. Dot plot analysis,
      however, reveals a surprisingly well-conserved sequence similarity over the
      entire analyzed region. In particular, the positions of CpG islands, short
      regions of very high GC content in the 5' region of putative genes, are similar
      in human and mouse. With respect to base composition, two distinct segments of
      significantly different GC content exist as well in human as in the mouse. With a
      GC content of 45% the one segment would correspond to "isochore H1" and the other
      segment (39% GC in human, 40% GC in mouse) to "isochore L1/L2". The gene density
      (one gene per 66 kb) is slightly higher than the average calculated for the
      complete human genome (one gene per 90 kb). The comparison of the number and
      distribution of repetitive elements shows that the proportion of human DNA made
      up by interspersed repeats (43.8%) is significantly higher than in the
      corresponding mouse DNA (30.1%). This partly explains why the human DNA is longer
      between the landmark genes used to define the orthologous positions in human and
      mouse.

PMID- 11528128
TI  - Chromosome homologies between man and mountain zebra (Equus zebra hartmannae) and
      description of a new ancestral synteny involving sequences homologous to human
      chromosomes 4 and 8.
AB  - Using human chromosome painting probes, we looked for homologies between human
      and mountain zebra (Equus zebra hartmannae, Equidae, Perissodactyla) karyotypes.
      Except for two very short segments, all euchromatic regions were found to have a
      human homologous chromosome segment. Conserved syntenies previously described in
      various mammalian orders were detected. Each synteny corresponded to a
      chromosomal region homologous to two parts of human chromosomes: HSA3 and HSA21,
      HSA7 and HSA16, HSA12 and HSA22, and HSA16 and HSA19. Chromosomal segments
      homologous to a part of HSA11 and HSA19p are found syntenic in zebra, horse and
      donkey, suggesting that this group of synteny has been inherited from an Equidae
      or Perissodactyla common ancestor. A synteny of segments homologous to parts of
      HSA4 and HSA8 was observed in zebra and horse. It also exists in the rabbit
      (Lagomorpha) and several Carnivora species. A second group of taxa which does not
      have this region of synteny is composed of primates, Chiroptera and Insectivora,
      and possibly also Cetacea and Scandantia. Thus, the presence or absence of this
      region of synteny may separate two groups of eutherian mammals.

PMID- 11528129
TI  - Integration of porcine chromosome 13 maps.
AB  - In order to expand the comparative map between human chromosome 3 (HSA3) and
      porcine chromosome 13 (SSC13), seven genes from HSA3 were mapped on SSC13 by
      fluorescence in situ hybridisation (FISH), viz. ACAA1, ACPP, B4GALT4, LTF, MYLK,
      PDHB and RARB. With a view to integrating this expanded comparative map with the
      existing SSC13 linkage map, we used the INRA-University of Minnesota porcine
      Radiation Hybrid panel (IMpRH) to localize more precisely and to order 15 genes
      on the SSC13 map, viz. ACPP, ADCY5, APOD, BCHE, CD86, DRD3, GAP43, PCCB, RAF1,
      RHO, SI, TF, TFRC, TOP2B and ZNF148. In this way, we were able to create an
      integrated map, containing 38 type I and 81 type II markers, by correlating the
      linkage, radiation hybrid (RH) and cytogenetic maps of SSC13. This integrated map
      will give us the opportunity to take maximal advantage of the comparative mapping
      strategy for positional candidate cloning of genes responsible for economically
      important traits.

PMID- 11528130
TI  - Centromere and telomere redistribution precedes homologue pairing and terminal
      synapsis initiation during prophase I of cattle spermatogenesis.
AB  - Alterations in nuclear topology associated with meiotic chromosome pairing were
      studied in premeiotic cells and spermatocytes I of adult bovine males. To this
      end, we performed FISH with chromosome, pericentromeric satellite-DNA and
      telomere-specific probes in combination with immunostaining of synaptonemal
      complex proteins (SCP3, SCP1) on testis tissue sections. Nuclei of premeiotic
      cells (spermatogonia) exhibited a scattered telomere distribution while
      pericentromeres formed a few intranuclear clusters. We observed that the
      chromosome pairing process in cattle prophase I is preceded by repositioning of
      centromeres and telomeres to the nuclear periphery during preleptotene.
      Clustering of chromosome ends (bouquet formation) was observed during the
      transition from leptonema to zygonema and coincided with pairing of a sub
      centromeric marker of bovine chromosomes 7. Dissolution of bouquet topology
      during zygonema left perinuclear telomeres scattered over the nuclear periphery
      at pachynema. SCP3 staining in frozen tissue sections revealed the appearance of
      this axial element protein in intranuclear aggregates during preleptotene,
      followed by extensive axial element formation during leptotene. Synapsis as
      revealed by SCP1 staining initiated peripherally at earliest zygotene, at this
      stage nuclei still contained numerous SCP3 clusters. Our observations reveal
      prominent non-homologous satellite-DNA associations in spermatogonia and indicate
      the conservation of topological features of the meiotic chromosome pairing
      process among mammals. The comparison of telomere dynamics in mouse and cattle
      prophase I suggests that a larger number of chromosomes prolongs the duration of
      the bouquet stage.

PMID- 11528131
TI  - Assignment of the SMARCF1 gene to tammar wallaby chromosome 5q by fluorescence in
      situ hybridisation.

PMID- 11528133
TI  - Peritoneal adhesions: etiology, pathophysiology, and clinical significance.
      Recent advances in prevention and management.
AB  - AIM: To summarize the most common etiologic factors and describe the
      pathophysiology in the formation of peritoneal adhesions, to outline their
      clinical significance and consequences, and to evaluate the pharmacologic,
      mechanical, and surgical adjuvant strategies to minimize peritoneal adhesion
      formation. METHODS: We performed an extensive MEDLINE search of the
      internationally published English literature of all medical and epidemiological
      journal articles, textbooks, scientific reports, and scientific journals from
      1940 to 1997. We also reviewed reference lists in all the articles retrieved in
      the search as well as those of major texts regarding intraperitoneal postsurgical
      adhesion formation. All sources identified were reviewed with particular
      attention to risk factors, pathophysiology, clinical manifestations, various
      methods, and innovative techniques for effectively and safely reducing the
      formation of postsurgical adhesions. RESULTS: The formation of postoperative
      peritoneal adhesions is an important complication following gynecological and
      general abdominal surgery, leading to clinical and significant economical
      consequences. Adhesion occur in more than 90% of the patients following major
      abdominal surgery and in 55-100% of the women undergoing pelvic surgery. Small
      bowel obstruction, infertility, chronic abdominal and pelvic pain, and difficult
      reoperative surgery are the most common consequences of peritoneal adhesions.
      Despite elaborate efforts to develop effective strategies to reduce or prevent
      adhesions, their formation remains a frequent occurrence after abdominal surgery.
      CONCLUSIONS: Until additional information and findings from future clinical
      investigations exist, only a meticulous surgical technique can be advocated in
      order to reduce unnecessary morbidity and mortality rates from these untoward
      effects of surgery.

PMID- 11528134
TI  - Extracorporal resection of the rectum in the treatment of complete rectal
      prolapse using a circular stapling device.
AB  - BACKGROUND AND PATIENTS: The technique of the extracorporal resection of the
      rectum using a circular stapler in the treatment of complete rectal prolapse is
      described on the basis of 31 successfully applied operations at the Surgical Unit
      in Dusseldorf-Gerresheim. RESULTS: The easy-to-perform operation does not require
      general anaesthesia, the incidence of peri-operative complications (5/31) and
      lethality (1/31) is acceptable and post-operative recovery is fast due to less
      physiologic insult as compared to transabdominal procedures. The recurrence rates
      (0/22) stand the comparison with transabdominal procedures. The operation can be
      re-performed in the case of a recurrent prolapse. CONCLUSIONS: Our good results
      show that the perineal rectosigmoidostomy using a circular stapler is a safe and
      efficient means of controlling rectal prolapse. Many advantages in comparison
      with transabdominal procedures make it an attractive option for many patients
      suffering from rectal prolapse.

PMID- 11528135
TI  - Portal venous air and pneumatosis intestinalis.

PMID- 11528136
TI  - Immunocytochemical detection of tumour cells in the thoracic duct of patients
      with an adenocarcinoma of the oesophagus.
AB  - BACKGROUND: Compared to other hollow viscus organs, the oesophagus has a unique
      anatomy in which lymphatic channels are abundantly present in the mucosa and
      submucosa. It has been hypothesized that tumour cells can directly disseminate
      from these superficial layers into the thoracic duct without passing juxta
      tumoral lymph nodes. We investigated whether tumour cells of an oesophageal
      carcinoma could be detected in the thoracic duct during operative manipulation.
      METHODS: In patients with an adenocarcinoma of the oesophagus and/or gastro
      oesophageal junction, undergoing a transthoracic resection with two-field
      lymphadenectomy, lymph was collected and cells were immunostained. RESULTS:
      Tumour cells could be detected in the thoracic duct lymph of only 1 out of 19
      patients during operative manipulation. CONCLUSION: Peroperative data from this
      study do not support the hypothesis that oesophageal carcinoma readily
      metastasizes directly into the thoracic duct.

PMID- 11528137
TI  - Single and multiple pyogenic liver abscesses: etiology, clinical course, and
      outcome.
AB  - BACKGROUND: Pyogenic liver abscesses are uncommon but they still carry a high
      mortality rate when encountered. This study was undertaken to evaluate the
      differences in the clinical behaviour of patients with single and multiple
      abscesses. METHODS: From January 1985 to December 1997, 133 patients with this
      disease were treated in the surgical departments of five hospitals, 97 had a
      single abscess and 36 had multiple abscesses. Clinical features, methods of
      treatment, and outcome were assessed and compared in both types of abscesses.
      RESULTS: A biliary origin from ascending cholangitis was most frequently found in
      multiple abscesses (p = 0.007). Mean age and duration of symptoms were higher in
      multiple lesions (p = 0.03 and p = 0.001). High levels of alkaline phosphatase
      were more frequently seen in multiple abscesses than in solitary ones (p = 0.02).
      They were both most frequently located on the right side. Antibiotic therapy
      alone was most frequently used in multiple abscesses (p = 0.01). Mortality rate
      was also higher in this type of patients (p = 0.01). The abscess-related
      morbidity rate was higher in multiple lesions as well but the statistical
      difference was not significant. CONCLUSIONS: These results suggest that multiple
      liver abscesses comprise a disease of biliary origin, higher age, longer
      symptomatic periods, and also higher mortality rate than in single abscess.

PMID- 11528139
TI  - Treatment of adrenal metastases after hepatic resection of a hepatocellular
      carcinoma.
AB  - BACKGROUND: The adrenal gland is a common site of extrahepatic metastases from a
      hepatocellular carcinoma (HCC). However, treatment of adrenal metastases has not
      been well characterized. METHODS: Of 562 patients who underwent hepatic resection
      for a HCC, 91 developed extrahepatic metastases. We reviewed the medical records
      of 10 patients with adrenal metastases (9 males and 1 female; mean age 63 years
      at the time of hepatic resection). RESULTS: The mean diameter of the primary
      tumors was 5 cm, and all were located in the right lobe of the liver. The mean
      interval from hepatic resection to recurrence was 18 months. Seven patients
      underwent treatment of intrahepatic recurrence. To treat the adrenal metastases,
      surgical resection was performed in 4 patients, and transcatheter arterial
      embolization was performed in 1 patient. The patients treated had no other
      extrahepatic metastases. The mean diameter of the resected adrenal tumors was 6
      cm. There was no hospital mortality. With surgical resection, 1 patient has been
      alive 63 months after recurrence. CONCLUSIONS: Adrenal metastases from a HCC were
      often large at the time of diagnosis. Since surgical resection was a safe
      procedure, and some patients could be alive for a long time, it should be
      performed whenever possible.

PMID- 11528138
TI  - Surgical treatment of intrabiliary rupture of hydatid cysts of liver: comparison
      of choledochoduodenostomy with T-tube drainage.
AB  - BACKGROUND: Intrabiliary rupture is one of the most serious complications of
      liver hydatid cysts (LHC). The kind of surgery for these patients is still
      controversial. T-tube drainage and choledochoduodenostomy (CD) are used by most
      of the surgeons. But there is no comparative study in the literature. METHODS:
      Eighty patients with symptomatic intrabiliary rupture were treated between 1980
      and 1995. All patients had jaundice. In addition to treatment of the cyst cavity,
      T-tube drainage of the common bile duct (CBD) was performed in 53 patients, 25
      patients underwent a CD for biliary drainage and two patients were treated by a T
      tube placed in the CBD without treating the cyst. The T-tube drainage and CD
      groups were compared in regard to morbidity, mortality, duration of the
      operation, rate of relaparatomy and duration of postoperative hospital stay.
      RESULTS: The morbidity rate was 40% (10/25) after CD and 18.1% (10/55) after T
      tube drainage. Relaparatomy was necessary in 8% (2/25) and 1.8% (1/55) of
      patients treated with CD and T-tube drainage, respectively. T-tube drainage was
      performed much more rapidly than CD (p < 0.05). The length of hospital stay for
      both groups was the same. One patient who was treated with CD died
      postoperatively. CONCLUSION: Our results suggest that T-tube drainage is superior
      to CD for intrabiliary rupture of LHC in most cases.

PMID- 11528140
TI  - Dye-staining stereomicroscopic examinations for fine mucosal structures of the
      gallbladder.
AB  - BACKGROUND: In order to diagnose an unsuspected gallbladder carcinoma and to
      examine whether a differential diagnosis could be made between cancer and
      noncancerous lesions during surgery, we evaluated the findings of fine structures
      of various types of gallbladder mucosa. METHODS: We used stereomicroscopy with a
      dye-contrast technique under water and measured the maximum blood vessel
      diameters of the gallbladder mucosa: normal gallbladder, chronic cholecystitis,
      and carcinoma. RESULTS: All normal gallbladders showed fine-reticular-type
      findings. In chronic cholecystitis, 5.8% of the specimens (n = 69) had fine
      reticular type, 87.0% had rough reticular type, and 7.2% had atrophic type. All
      the cases of adenomyomatosis (n = 16) showed rough reticular type. In eight
      specimens of pancreaticobiliary maljunction, 75% of them showed high reticular
      type, and the other 25% showed papillary type. The two adenoma specimens showed
      fine granular type. In five gallbladder carcinomas, the lattice-like pattern
      completely disappeared and showed rough granular type. The average of maximum
      vessel diameters in the gallbladder mucosa were 41.0 microm in normal
      gallbladders, 99.1 microm in patients with chronic cholecystitis, and 614.8
      microm in patients with a carcinoma. There were significant differences among
      them (p < 0.05). CONCLUSION: This study showed that differential diagnosis
      between cancer and noncancerous lesion is possible by dye-staining mucosal
      pattern and measurement of maximum vessel diameters by stereoscopic examination.

PMID- 11528141
TI  - Effects of propranolol on human postoperative ileus.
AB  - BACKGROUND: The sympathetic nervous hyperactivity present in response to surgical
      stress has been implicated as an important component of the postoperative
      paralytic ileus. A randomized and prospective study was conducted, evaluating the
      effects of the preoperative beta-adrenergic blockade with propranolol in
      schistosomotic patients during the period of postoperative ileus. METHODS: The
      study compared schistosomotic patients submitted, or not, to beta-adrenergic
      blockade. Basal cardiac frequency was determined and propranolol was used in a
      dose of 40 mg twice a day. The dose was adjusted weekly until a minimum decrease
      of 20% in cardiac frequency was achieved. Three coupled bipolar electrodes were
      placed in the left colon in both groups, and registration of myoelectric activity
      of the left colon was made twice a day during the period of postoperative ileus
      using a system of data collection (DATA Q Series 200). The electric signals were
      previously amplified, filtered and separated into Electric Control Activity (ECA)
      and Electric Response Activity (ERA). RESULTS: The dose of propranolol varied
      from 80 to 160 mg/day. The proportional decrease in basal heart frequency varied
      from 20 to 33%, with an average of 25.4 +/- 3.9% in the propranolol group,
      maintaining a mean of 24.3 +/- 3.6% decrease in the postoperative period.
      Differences on clinical recovery of the postoperative ileus were not found.
      Significant differences on electromyographic patterns were not observed between
      the groups, except for the presence of a greater number of short-duration
      contractions in the second postoperative day in the beta-blocked group.
      CONCLUSION: The authors suggest that the preoperative beta-adrenergic blockade
      with propranolol does not determine myoelectric activity changes that could
      contribute to an earlier resolution of postoperative ileus.

PMID- 11528142
TI  - Theodor Kocher (1841-1917)--a surgical maestro.

PMID- 11528143
TI  - Biliary web--a rare cause of extrahepatic biliary obstruction.
AB  - A case of an isolated mucosal web of the common hepatic duct is presented. Such
      extrahepatic biliary webs are extremely rare causes of biliary obstruction,
      likely congenital in nature, but presenting in later life due to the initial
      patency of these webs in allowing bile drainage from the liver. The relevant
      literature is reviewed; diagnostic and therapeutic aspects are discussed.

PMID- 11528144
TI  - Successful left trisegmentectomy for polycystic liver disease accompanied by
      jaundice.
AB  - BACKGROUND: We report a case of severe polycystic liver disease (PLD) with
      jaundice in a 57-year-old woman who underwent successful left trisegmentectomy.
      METHOD: She was admitted for the first time in February 1992 to our hospital with
      a 7-year history of PLD, and became jaundiced in June 1995. Because normal liver
      parenchyma was confirmed mainly to the posterior segment, left trisegmentectomy
      was performed. RESULTS: No postoperative complication occurred. The serum
      bilirubin level decreased promptly after the operation, but postoperative
      endoscopic retrograde cholangiography showed that the root of the posterior
      hepatic duct remained thin. Thus, the elimination of jaundice was presumed to
      have been caused by a decrease of intra-abdominal and peripheral biliary
      pressure, since a large volume of tissue had been removed from the peritoneal
      cavity. She has since remained well without any symptoms. CONCLUSION: This
      procedure is useful for severe PLD, because it can be performed safely and the
      symptoms disappear dramatically. However, further follow-up is needed to
      determine the long-term effects of this procedure, because the remaining liver
      has shown some increase in size.

PMID- 11528145
TI  - Lipoma of the liver associated with hepatocellular carcinoma and polycystic liver
      disease.
AB  - BACKGROUND/AIMS: We report on a patient with lipoma of the liver associated with
      hepatocellular carcinoma (HCC) and polycystic liver disease. METHODS: Clinical
      features of a patient with lipoma, HCC and polycystic liver disease are
      presented. A right liver lobectomy was performed. RESULTS: Histological
      examination revealed a poorly differentiated multicentric HCC, as well as bile
      duct cysts and an encapsulated tumor of adipose tissue. The postoperative course
      was uncomplicated. The patient died 4 years after surgery with local recurrence
      of HCC. CONCLUSION: We find the report to be of interest because of the unusual
      nature of this association and the low prevalence of lipoma of the liver. The
      association of liver polycystic disease with other types of tumor is discussed
      and the literature dealing with lipomas of the liver reviewed.

PMID- 11528146
TI  - Splenic artery aneurysm rupture.
AB  - BACKGROUND: Splenic artery aneurysms are uncommon even though they are second
      only to those of the aorto-iliac system. There is also controversy regarding
      their management. METHODS: We report the case of a 50-year-old patient with
      ruptured splenic artery aneurysm and review the literature regarding its
      diagnosis and management. RESULTS: The patient underwent emergency laparotomy and
      splenectomy was performed. CONCLUSION: Resuscitation and an aggressive surgical
      approach should be taken in order to save the life of the patients.

PMID- 11528147
TI  - Pancreatic resection for cancer in a young patient with HIV infection.

PMID- 11528148
TI  - Focal intraperitoneal fat infarction.
AB  - Focal intraperitoneal fat infarction, e.g. epiploic appendagitis and segmental
      omentum infarction, may mimic almost every acute abdominal condition. The
      symptoms of this benign and self-limiting disease will disappear without
      treatment. The etiology, symptoms, diagnosis (mainly with ultrasound and CT scan)
      and course of the disease are being described. An atypical case history with
      uneventful recovery without medical or surgical treatment is presented.

PMID- 11528149
TI  - Neuromuscular and vascular hamartoma of the small intestine.
AB  - Neuromuscular and vascular hamartoma is an extremely rare stricturing condition
      of the small bowel. It consists of abnormal mixtures of intestinal tissues:
      disorganized fascicles of smooth muscle derived from the submucosa, bundles of
      nonmyelinated nerve fibers with scattered abnormal ganglion cells and
      hemangiomatous vessels, occurring focally and causing recurrent obstructive
      symptoms or occult chronic gastrointestinal bleeding. In this paper we report our
      experience with this tumor.

PMID- 11528150
TI  - Carcinoma of the colon metastatic to the lower gingiva.
AB  - A case of carcinoma of the colon that metastasized to the lower gingiva is
      described. The patient who had carcinoma of the colon developed a proliferating
      lesion at the site of a recent tooth extraction. A few days later, the primary
      site of the malignancy appeared. The clinical features in such cases were
      reviewed in studies by others, most of which were of oral and dental surgery.
      Thus, because of our case, gastroenterologists should consider the possibility of
      gingival metastasis from malignant disease such as colorectal cancer.

PMID- 11528151
TI  - Dermoid cyst of the colon.
AB  - Dermoid cysts are benign cystic teratomas lined by skin and epidermal appendages.
      We report a dermoid cyst occurring in a 26-year-old female whose chief complaint
      was irregular vaginal bleeding. Abdominal magnetic resonance image demonstrated a
      space-occupying lesion in the right lower abdomen. The mass showed hyperintensity
      on the T2 image and the signal was homogeneous for the interior. During abdominal
      surgery we made the diagnosis of subserous tumor of the colon and resected the
      ileocecal portion of the colon. The tumor measured 5.4 x 4.8 x 3.5 cm and was
      soft and elastic. On cross section, a unilocular cyst filled with atheromatous
      material was found. Pathological examination revealed a dermoid cyst. In the view
      of this diagnosis, a simple excision would have been an adequate treatment.

PMID- 11528152
TI  - Reinforcement of extraperitoneal gastrointestinal anastomoses by omentum.

PMID- 11528153
TI  - The role of carotid stenosis in vascular cognitive impairment.
AB  - The role of carotid stenosis in vascular cognitive impairment was reviewed using
      Medline, EMBASE, PsychLit and PsychInfo databases using the words "carotid
      stenosis", "neuropsychological tests" and "endarterectomy". Limited evidence
      exists for frontal lobe dysfunction associated with carotid stenosis, but there
      is a lack of systematic and prospective studies carried out in consecutive
      patients, including appropriate neuropsychological and MRI assessment. Possible
      pathophysiological processes suggested for cognitive impairment associated with
      carotid stenosis are suggested; these include chronic ischaemia and lacunar
      infarction; such mechanisms and resultant pathologies may co-exist in the
      presence of large-artery atheroma.

PMID- 11528154
TI  - Hypertension and neurovascular compression of the left lateral medulla oblongata
      in ischemic stroke.
AB  - Hypertension is a major risk factor for stroke. Neurovascular compression (NC) of
      the left ventrolateral medulla oblongata may cause arterial hypertension. We
      evaluated the relationship between the two ischemic stroke patients. We
      classified 69 patients under 50 years old (49 men and 20 women, aged 43.6 +/- 7.3
      years) based on magnetic resonance imaging findings as follows: NC patients (n =
      38; 10 with NC on the right side, 18 with NC on the left side, and 10 with NC on
      both sides) and non-NC patients (n = 31). We compared the following clinical
      characteristics between the two groups: (1) risk factors for stroke, including
      hypertension, diabetes mellitus, hypercholesterolemia, and smoking and (2) stroke
      subtype. Hypertension was more frequent in the NC group than in the non-NC group
      (58 vs. 19%, p = 0.001). Hypertension was more frequent in patients with left
      side NC than in those with right-side NC (78 vs. 20%, p = 0.005). No other
      differences were observed between the two groups. Twelve patients presented with
      atherothrombotic stroke, 16 with cardioembolic stroke, 24 with lacunar stroke and
      17 with stroke of miscellaneous etiology. NC was significantly more common in
      patients with lacunar stroke as compared with those affected by other stroke
      subtypes (p = 0.015). We found a significant relationship between hypertension
      and NC of the ventrolateral medulla oblongata on the left side in ischemic stroke
      patients younger than 50 years of age. Some patients with lacunar stroke may have
      hyptertension related to NC.

PMID- 11528155
TI  - Orbicularis oculi and orbicularis oris reflexes in blepharospasm and torticollis
      spasmodica during spasm-free intervals.
AB  - To investigate possible abnormalities of the blink reflex pathways, we analyzed
      the latencies and amplitudes of the blink reflex responses in the orbicularis
      oculi (Ooculi) muscle, following supraorbital nerve stimulation, in 19 patients
      with blepharospasm, 16 patients with torticollis spasmodica and 22 control
      subjects. Furthermore, in order to examine the suprasegmental control of the
      responses, the reflex responses were also evoked in the orbicularis oris (Ooris)
      muscle after stimulation of the ipsilateral supraorbital nerve. The responses
      were recorded only when subjects had no contractions of the eyelid muscles,
      either involuntarily, voluntarily or spontaneously; this could be controlled by a
      sound signal. The metrics of the reflex responses in the Ooculi and Ooris muscles
      in patient groups were comparable to those in controls. Our data indicate that
      the afferent and efferent pathways of the reflex arc and the suprasegmental
      control of the reflex are intact in patients with blepharospasm and torticollis
      spasmodica, at least during spasm-free intervals. Alterations of responses may
      occur during spasms due to either segmental or suprasegmental changes.

PMID- 11528156
TI  - Mycophenolate mofetil in the therapy of severe myasthenia gravis.
AB  - Mycophenolate mofetil is a novel immunosuppressive drug already established in
      transplantation medicine. Recently, results of three open clinical trials on
      mycophenolate mofetil in myasthenia gravis have been reported. Mycophenolate
      mofetil in a dose of 1.0-2.0 g/day was given in 2 patients with severe refractory
      myasthenia gravis and in 1 patient with myasthenia gravis-polymyositis syndrome.
      Apart from dose-dependent reversible hemolytic anemia in 1 patient, no severe
      side effects occurred. Considerable improvement of myasthenic symptoms was seen
      in all patients within 3-6 months after the initiation of this therapy.
      Mycophenolate mofetil may be considered as a useful alternative in the treatment
      of severe myasthenia gravis when standard therapeutic regimens fail. It is
      usually well tolerated and its application is simple.

PMID- 11528157
TI  - Guillain-Barre syndrome in Spain, 1985-1997: epidemiological and public health
      views.
AB  - Retrospective demographic information and hospital record data were collected for
      337 patients resident in Spain who had validated Guillain-Barre syndrome (GBS)
      diagnoses and clinical onset during the period 1985-1997 and had been admitted to
      11 centres, covering a population of 3.9 million. The European age-adjusted GBS
      incidence per 100,000 for 1985-1997 among the population aged 20 and over was
      0.85, with a breakdown of 1.14 in men and 0.58 in women. Incidence increased with
      age and time, with occasional rises that mimicked outbreaks and occurred at
      irregular 2- to 4-year intervals, mainly in winter. Spatial variation was modest.
      Respiratory and gastrointestinal infections respectively constituted 49.3 and
      19.3% of recorded preceding events. The 97.5% intercentile limit, obtained from
      the 1985-1997 monthly incidences using predictions from a Poisson model, was
      proposed as the threshold value for pilot epidemiological surveillance of GBS in
      1998-1999.

PMID- 11528158
TI  - Nail-patella syndrome associated with respiratory chain disorder.
AB  - Nail-patella syndrome (NPS) has not been described to be associated with a
      respiratory chain disorder (RCD) before. In a 42-year-old man with the typical
      phenotype of an NPS, weakness and wasting of the shoulder girdle muscles, muscle
      cramps, fatigability, hyperhidrosis, chest pain and creatine kinase elevation
      were observed. Echocardiography revealed left ventricular hypertrabeculation.
      Needle electromyography was myopathic, lactate stress testing was abnormal,
      muscle biopsy showed typical features of an RCD and mtDNA analysis revealed the
      A3243G MELAS mutation. In conclusion, this case demonstrates that NPS may be
      randomly associated with RCD. NPS patients should undergo detailed cardiological
      and neurological investigations, in order not to overlook a double trouble
      partially mimicking NPS.

PMID- 11528159
TI  - Neglect in radial and vertical axes after a unilateral left temporo-occipital
      lesion.

PMID- 11528160
TI  - Amaurosis fugax associated with phencyclidine inhalation.

PMID- 11528161
TI  - Propriospinal negative myoclonus.

PMID- 11528162
TI  - Focal hyperperfusion on (99m)Tc ECD SPECT in a patient with epileptic aphasia.

PMID- 11528163
TI  - Acute disseminated encephalomyelitis following Leptospira infection.

PMID- 11528164
TI  - Posterior cerebral artery infarction caused by cerebral sparganosis-induced
      vasculitis.

PMID- 11528165
TI  - A preliminary, randomized, multicenter study comparing intravenous
      immunoglobulin, plasma exchange, and immune adsorption in Guillain-Barre
      syndrome.

PMID- 11528166
TI  - Detection of posterior ischemic optic neuropathy due to giant cell arteritis with
      magnetic resonance imaging.

PMID- 11528167
TI  - Rivastigmine in the treatment of Alzheimer's disease.

PMID- 11528170
TI  - Proposal for a "European Scoring System for Laparoscopic Operations in Urology".
AB  - PURPOSE: To propose a scoring system of difficulties for the most currently
      performed laparoscopic procedures in urology. MATERIALS AND METHODS: Each current
      laparoscopic procedure has been evaluated according to three different criteria:
      technical difficulty, operative risk and the attention required. Each criterion
      is scored from 1 (minimal impact of the criteria) to 7 (maximal impact of the
      criteria). The sum of the 3 criteria is used to classify each operation according
      to an increasing level of global difficulty, classified into 6 levels: easy (E:
      sum of criteria between 3 and 5), slightly difficult (SD: sum of criteria between
      6 and 8), fairly difficult (FD: sum of criteria between 9 and 11), difficult (D:
      sum of criteria between 12 and 14), very difficult (VD: sum of criteria between
      15 and 17), extremely difficult (ED: sum of criteria greater than 18). RESULTS:
      Procedures currently performed by laparoscopy have been selected for evaluation
      according to the above criteria, and retrospectively validated by European
      experts in laparoscopic urology according to their experience and the
      international literature. CONCLUSION: This proposal of a scoring scale system is
      a basis for discussion, teaching and learning of urological laparoscopy. By
      necessity, this scale is evolving and will be regularly reconsidered and updated
      every 5 years.

PMID- 11528171
TI  - Current role of laparoscopic adrenalectomy.
AB  - OBJECTIVE: Laparoscopic adrenalectomy is now a standard procedure for the vast
      majority of patients with surgical adrenal disease. Herein, we evaluate various
      techniques employed during laparoscopic adrenalectomy, and assess the current
      role of laparoscopic adrenalectomy, and possible future developments. MATERIALS
      AND METHODS: We reviewed large series of reports presenting the results of
      laparoscopic transperitoneal and retroperitoneal adrenalectomy and we compared
      the data of different series and authors, adding our experience. RESULTS:
      Laparoscopic adrenalectomy is a safe, reproducible and effective procedure with
      low complication rates. With increasing worldwide experience, the indications for
      laparoscopic adrenalectomy are expanding. When retrospectively compared to open
      surgery, laparoscopic adrenalectomy is superior in terms of postoperative pain,
      hospital stay, return to normal activity and complications. CONCLUSIONS:
      Laparoscopic adrenalectomy is a safe and effective option for most surgical
      adrenal pathologies. Moreover, laparoscopic adrenalectomy is associated with a
      superior patient tolerance profile. It is safe to say that today, laparoscopy
      must be considered the first choice procedure for excision of benign surgical
      adrenal lesions.

PMID- 11528172
TI  - Laparoscopic radical nephrectomy.
AB  - Laparoscopic radical nephrectomy has gained in popularity as an accepted
      treatment modality for localized renal cell carcinoma at many centers worldwide.
      Laparoscopic radical nephrectomy may be performed via a transperitoneal or
      retroperitoneal approach. Mostly, the transperitoneal approach is used. Current
      indications for laparoscopic radical nephrectomy include patients with T(1)
      T(3a)N(0)M(0) renal tumors. Herein, transperitoneal as well as retroperitoneal
      laparoscopic approaches are described. Surgical outcomes and complications from
      published series are reviewed with comparison to open surgery. Special related
      concerns as oncologic principles, organ retrieval, lymphadenectomy, and
      concomitant adrenalectomy are addressed. In conclusion, laparoscopic radical
      nephrectomy is now established with considerable advantages; decreased
      postoperative morbidity, decreased analgesic requirements, improved cosmesis,
      shorter hospital stay and convalescence. Although no long-term follow-up is
      available, short and intermediate follow-up results confirm the effectiveness of
      laparoscopic radical nephrectomy.

PMID- 11528173
TI  - Nonrandomized comparison of open flank versus laparoscopic nephrectomy in 249
      patients with benign renal disease.
AB  - OBJECTIVES: We report the results from a nonrandomized comparison of open flank
      versus laparoscopic nephrectomy in patients with benign renal disease. METHODS:
      From January 1993 to December 1997, 249 nephrectomies for benign renal disease
      were performed at our institution. There were 118 patients in the open flank
      nephrectomy group (median age 58.5, range 8-89 years) and 131 patients in the
      laparoscopic nephrectomy group (median age 40, range 16-73 years). Clinical
      parameters such as operative times, blood loss, transfusion rates, conversion and
      complication rates, start of oral intake, analgesic consumption, duration of
      hospitalization and convalescence and short-term mortality were compared among
      both groups. RESULTS: Median operative time in the open flank nephrectomy group
      was 90 (range 30-240) min and also 90 (range 41-210) min in the laparoscopic
      nephrectomy group. In the laparoscopy group 8 patients were converted to open
      surgery (6.1%). There were 27 complications (20.6%) in the laparoscopic
      nephrectomy group compared to 30 complications (25.4%) in the open flank
      nephrectomy group. Postoperatively, patients in the laparoscopic nephrectomy
      group required less morphine sulfate equivalent (12 vs. 20 mg) for pain control
      and they had a shorter hospital stay (4 vs. 10 days) and convalescence (24 vs. 36
      days). The postoperative parameters are given as medians and reached
      statistically significant differences in favor of laparoscopic nephrectomy.
      CONCLUSIONS: Laparoscopic nephrectomy results in a significantly briefer
      postoperative course when compared to open flank nephrectomy. As a matter of fact
      laparoscopy in urology is still a center-related procedure and even in these
      centers only a minority of urologists practice laparoscopy. However, in
      experienced centers the laparoscopic technique should be offered to patients with
      benign renal disease who are scheduled for elective nephrectomy.

PMID- 11528174
TI  - Laparoscopic versus open ureterolithotomy. A comparative study.
AB  - OBJECTIVE: The aim of this study is to compare the transperitoneal laparoscopic
      ureterolithotomy versus conventional open surgery in cases of ureteric stones
      which failed to be treated endoscopically. MATERIALS AND METHODS: In this study,
      the clinical results of 18 transperitoneal laparoscopic ureterolithotomies (TLU)
      are compared with 18 open ureterolithotomies (OU) for impacted or large stones of
      the upper and middle portion of the ureter that were unable to be disintegrated
      with extracorporeal shock wave lithotripsy (SWL) or endoscopically. In the
      analysis of the clinical data are included the operative time and the post
      operative morbidity, length of analgesia needed, hospital stay and convalescence
      period. RESULTS: All our laparoscopic procedures were accomplished successfully.
      The mean operation time was 130 min for TLU and 85 min for OU. Analgesic
      medication requirement per patient was 1 day for TLU and 4 days for OU while the
      postoperative hospital stay averaged 3 days for TLU and 8 days for OU and the
      time of convalescence was12 days for TLU and 22 days for OU. No patient required
      a blood transfusion and postoperative complications included urinary leak,
      subcutaneous hematoma, subcutaneous emphysema in the TLU group and wound
      cellulitis and urinary tact infections in the OU group. CONCLUSION: While most
      patients with ureteric calculi can be rendered stone-free with SWL and
      endourological procedures, open stone surgery continues to represent a reasonable
      alternative for a small segment of the urinary stone population. However, our
      results reveal distinct benefits of TLU when compared to OU and thus laparoscopy
      instead of open surgery should be preferred.

PMID- 11528175
TI  - Laparoscopic radical prostatectomy. The Creteil experience.
AB  - OBJECTIVES: In an effort to reduce the morbidity associated to radical
      prostatectomy, we implemented laparoscopic surgery to this advanced ablative and
      reconstructive procedure. In our study, we describe our operative technique and
      assess our results in terms of oncologic cure, continence and potency. METHODS:
      200 patients with clinically localized prostate cancer underwent laparoscopic
      radical prostatectomy. 66 of these patients were either referred, or operated
      during surgical demonstrations. Thus, complete evaluation is based on a
      homogeneous personal series of 134 patients and was performed by an independent
      clinical analyst. There were 91 T1 and 43 T2. We did not perform pelvic lymph
      node excision in 78 patients whose PSA was less than 10 ng/ml and the Gleason
      score of endorectal biopsies was below 7. The surgical procedure recapitulated
      the steps of traditional retropubic prostatectomy with one basic difference
      however: the first step of the technique consisted in a rectoprostatic cleavage,
      which was done transperitoneally. Except for the first 10 patients, the
      vesicourethral reconstruction was performed either with two hemi-circumferential
      or a single circumferential running suture. RESULTS: All interventions were
      performed as planned, no conversions were necessary, and only 4 patients required
      blood transfusion. Operating time decreased with growing experience; after the
      first 20 patients the usual operating time was 3.5 h without and 4 h with
      lymphadenectomy. The surgical complication rate was 22.5% in the first 40
      patients, and 3.2% in the remaining 94 patients. Except for the first 10
      patients, the mean hospital stay was 6.1 days and bladder catheterization 4.8
      days. Median catheterization time was 4 days. Histological study of the specimen
      showed pT2 disease in 101 patients and pT3 in 33 patients, the rate of positive
      margins was 16.8 and 48.8%, respectively. At 1 year, overall erection rate (with
      or without sexual intercourse) was 56%, the rate of patients without pad was
      86.2% during the day and 100% during the night. CONCLUSIONS: Laparoscopic
      environment seems to comply with the oncologic goals of radical prostatectomy.
      Improved intraoperative visualization and magnification may provide benefits for
      the preservation of continence and potency by allowing a more precise dissection
      and vesicourethral reconstruction. Despite longer operative times and the steep
      learning curve this new technique is currently proliferating due to expectations
      of decreased postoperative morbidity and better quality of life.

PMID- 11528176
TI  - Laparoscopic radical prostatectomy. Technical aspects and experience with 125
      cases.
AB  - PURPOSE: The laparoscopic access for radical prostatectomy offers an alternative
      to the open surgical procedure with less morbidity. We report on our experience
      with 125 laparoscopic prostatectomies, especially with respect to making the
      laparoscopic approach a routine procedure and with a view to the oncological and
      functional results. MATERIAL AND METHODS: From June 1999 to September 2000, we
      performed 125 laparoscopic prostatectomies. These included only patients with
      cancer stages T1 or T2. The mean PSA concentration was 10.5 ng/ml. Forty-four
      percent of the patients had undergone previous abdominal and 19% previous
      transurethral surgery. For our laparoscopic prostatectomies we used the
      descending technique. Free-hand laparoscopic suturing and in situ knot-tying
      technique were used for the urethrovesical anastomosis. The mobilized specimens
      were removed in an endobag via a muscle splitting incision. RESULTS: All 125
      procedures could be completed successfully. No case required conversion to open
      surgery. The average operating time was 255 min, the last 40 procedures taking
      200 min only. Mean blood loss was 185 ml. Two patients (2%) required
      postoperative blood transfusion. After an initial learning curve, catheter
      remained in place for an average of 5.5 days, and the average postoperative stay
      in hospital was 8 days. Intraoperative complications were seen in 5 patients
      (4%). In 13 patients (10.4%) postoperative complications were observed. 86% of
      the patients are continent 6 months postoperatively. Preservation of the
      neurovascular bundle and sexual potency is possible. CONCLUSION: Laparoscopic
      radical prostatectomy is an ambitious procedure with a steep learning curve,
      especially for the laparoscopic dissecting and suturing technique. The excellent
      sight for dissection results in a reduced blood loss and faster convalescence
      with an overall lower morbidity. Also with regard to oncological and functional
      (continence) results the minimally invasive access is at least equivalent to the
      open procedure. In our opinion, laparoscopic prostatectomy will be the future
      method of choice for radical prostatectomy.

PMID- 11528177
TI  - Heilbronn laparoscopic radical prostatectomy. Technique and results after 100
      cases.
AB  - INTRODUCTION: In 1999, Guillonneau and Vallancien presented a refined approach of
      a descending laparoscopic radical prostatectomy which based mainly on the primary
      access to the seminal vesicles and an improved suturing and knotting technique.
      Based on our own experience reconstructive laparoscopy as well as with open
      retropubic radical prostatectomy we have used a combined ascending/descending
      technique similar to open surgery. In this paper we want to describe our approach
      and to present the initial results with the Heilbronn technique. MATERIALS AND
      METHODS: A transperitoneal approach is used with a W-shaped arrangement of the
      trocars (13-mm umbilical port, 2 x 10 mm medial, 2 x 5 mm lateral ports). After
      the exposure of the Retzius' space and control of the dorsal vein complex the
      urethra is incised and the distal pedicles of the prostate (+/- the neurovascular
      bundle) are transsected. We now pull the apex ventrally and start with the
      incision at the bladder neck followed by a transvesical access to both vasa
      deferentia and seminal vesicles. The gland is entrapped in the Extraction Bag.
      After accomplishing the posterior wall of the urethrovesical anastomosis with
      five interrupted sutures, the foley catheter is placed into the bladder and the
      bladder neck is closed. Now the prostate is extracted via the umbilical incision.
      From March 1999 to June 2000, we have performed 100 cases (48 pT2-, 47 pT3- and 5
      pT4 tumors). The mean preoperative PSA was 26.8 (1.4-75.5) ng/ml. Two tumors were
      grade 1, 72 grade 2 and 26 grade 3. Median Gleason score was 6 (3-9). All
      specimen were inked and examined according to the Stanford protocol.
      Postoperative continence was evaluated using a questionnaire monitored by a
      colleague who was involved in surgery. RESULTS: We had 5 conversions (rectal
      injury, difficult dissection, adhesion, 2x bleeding at the dorsal vein complex).
      The mean operating time was 278 (180-500) min., the transfusion rate 31%. One
      patient required reintervention due to bleeding from the right obturator fossa.
      95% of the patients did not require any analgesia on the second postoperative
      day. Positive margins were found in 17% of the patients, of which 12 had a PSA
      nadir to a value of less than 0.1 ng/ml within 3 weeks after surgery. In 82
      patients, the anastomosis was tight after removal of the catheter, median
      catheter time was 8 (6-30) days. 4% developed a stricture at the anastomotic site
      which could be treated by laser incision. On discharge 33% were continent, after
      6 months 81%, whereas only 2 patients still suffer from grade II stress
      incontinence at 9 months. CONCLUSIONS: Laparoscopic radical prostatectomy is
      feasible but requires laparoscopic expertise. Its learning curve is still
      ongoing. Morbidity is low, oncological control is similar to results of open
      surgery, functional results are promising.

PMID- 11528178
TI  - Extraperitoneal laparoscopic radical prostatectomy. Results after 50 cases.
AB  - INTRODUCTION: After an initial experience using transperitoneal laparoscopic
      radical prostatectomy as described by Vallancien and Guillonneau, we developed a
      pure extraperitoneal approach. This approach seems more comparable to the open
      technique and avoid potential risks of specific complications due to the
      transperitoneal approach. We evaluated the perioperative parameters (blood loss,
      operating time, transfusion rate) and postoperative results (oncological results,
      continence and potency) after our first 50 cases. MATERIAL AND METHOD: Between
      September 1999 and September 2000, we performed 50 laparoscopic radical
      prostatectomy. On average, patients were 63.3 years old (range 47-71), had
      preoperative mean PSA values of 9.14 ng/ml (1.1-23). Median Gleason score was 6
      (4-10) with 2.5 (1-6) positive biopsies for a mean prostate volume of 40 cm(3)
      (17.5-95.0). Clinical stage was T1, T2a, T2b and T3 in 46.3, 41.5, 9.8 and 2.4%
      of the cases, respectively. We used a pure extraperitoneal approach and we
      performed a descending technique starting with the dissection at the bladder
      neck. The seminal vesicles dissection is comparable to the open approach.
      RESULTS: 42 extraperitoneal and 8 transperitoneal procedures were performed (2 in
      the initial experience, 3 because of previous abdominal surgery and 3 because of
      incidental peritoneal opening). Mean operative time was 317 min, mean blood loss
      680 cm(3), transfusion rate of 13%. 1 patient/50 was converted to an open
      procedure. Pathological stage was pT1a, pT2a, pT2b, pT2c, pT3a and pT3b in 2.2,
      8.5, 42.5, 2.2, 34 and 10.6% of cases, respectively. Positive surgical margins
      were observed in 22% of cases. The potency rate after neurovascular bilateral
      bundle preservation was 43% at 3 months (n = 7) and 67% at 6 months and (n = 6)
      without any further treatment. The continence rate (no pad) was 39% at 3 months
      and 85% at 6 months. Detectable postoperative PSA at 3 month was observed in 2
      patients only. Two major complications occurred: one acute transient renal
      failure one uretrorectal fistula at day 20. CONCLUSIONS: The extraperitoneal
      laparoscopic radical prostatectomy results seem comparable to transperitoneal
      laparoscopic radical prostatectomy or open surgery. This approach is reproducible
      and seems to avoid the potential risks of intraperitoneal injury. Long-term
      follow up and comparative series are however necessary to further evaluate these
      new techniques.

PMID- 11528179
TI  - Robotically assisted laparoscopic radical prostatectomy: feasibility study in
      men.
AB  - PURPOSE: We report our early experience of robotically assisted laparoscopic
      radical prostatectomy. MATERIAL AND METHODS: Five consecutive patients, with an
      average age of 58 years, PSA 12, 1.6 positive biopsies, Gleason score 6, were
      operated in our institution over a period of 1 week by the same surgeon. A
      robotically assisted laparoscopic nerve sparing radical prostatectomy was
      performed according to the Montsouris technique with the Da Vinci robot
      (Intuitive Inc., Mountain View, Calif., USA). RESULTS: The mean installation time
      was 93 min (range 76-149). The mean operating time (starting at the dissection of
      the seminal vesicles until the final stitch of the anastomosis) was 222 min
      (range 150-381 min). The average blood loss was 800 cm(3) (range 700-1,600
      cm(3)). No postoperative complications were seen. Bladder catheter time: 6.5
      days, hospital stay 5.5 days, urine leak 1/5, continence 4/5, positive margin
      1/5. CONCLUSION: After this short experience, we conclude that: The use of a tele
      manipulation system accompanied by a three-dimensional view of the operating
      field provides a real benefit for the surgeon, and the urethro-anastomosis is
      easier to perform. The benefit for the patient is presently not very clear in
      terms of operating time, postoperative course and functional results, our initial
      results show that the robotically assisted procedure is at least as safe and
      effective as the conventional laparoscopic procedure.

PMID- 11528180
TI  - Telesurgical laparoscopic radical prostatectomy. Initial experience.
AB  - INTRODUCTION: Telepresence surgery offers theoretically to overcome two main
      problems of laparoscopic surgery, i.e. the limitation to only four degrees of
      freedom and the lack of stereovision. Since 1998, telesurgical minimally invasive
      procedures have been performed with the da Vinci system mainly for cardiac bypass
      surgery. Clinical experience in urology is still very limited. We want to present
      our initial experience using the device for robot-assisted laparoscopic radical
      prostatectomy. MATERIAL AND METHODS: The Intuitive surgical system consists of
      two main components: the surgeon's viewing and control console with 3D imaging
      and the surgical arm unit that positions and maneuvers detachable surgical
      instruments. These instruments introduced via two 8-mm trocars allow movements in
      all 6 degrees of freedom due to the EndoWrist technology. The surgeon performs
      the procedure seated at the console holding specially designed instruments.
      Highly specialized computer software and mechanics transfer the surgeon's hand
      movements exactly to the microsurgical movements of the manipulators at the
      operative site. We have used a semilunar-shaped 5-trocar arrangement with the
      robot's arms at the lateral trocars and two assistant trocars medially. A sixth
      trocar was used in the right suprapubic area for retraction of the gland. The
      left assistant used different instruments such as bipolar forceps, Ultracision,
      Endoclip, whereas the right assistant mainly used the suction-irrigation device.
      Except the first case, the Intuitive System was attached after exposure of
      Retzius' space. RESULTS: We have treated 6 patients (2 pT2, 4 pT3, median Gleason
      score 6). The OR time averaged 315 (242-480) min including pelvic lymph node
      dissection. No intraoperative complications occurred, 1 patient required
      transfusions. There were no positive margins, median catheter time was 5 days. 3
      patients were completely continent after 1 month. CONCLUSION: Telerobotic
      laparoscopic surgery offers several advantages over all presently available
      techniques, such as all six degrees of freedom, dexterity enhancement, tremor
      filtering, and stereovision. There is a learning curve with the device, mainly
      because of the magnification, the 3D image and the lack of tactile feedback.
      However, only after a short period of time, the experienced surgeon is able to
      get familiar with the device. However, there are still concerns with respect to
      the high investment and running costs of the device as well as regarding the
      necessity of further developments of instruments for urological procedures.

PMID- 11528181
TI  - Future developments and perspectives in laparoscopy.
AB  - INTRODUCTION: As urologists head into the new millennium, it has become clear
      that laparoscopy will play a significant role in successful urologic practice.
      Issues that are addressed in this article include: (1) What are the new limits?
      (2) Technological advances. (3) Adequate training. (4) How to technically
      simplify the laparoscopic procedures? MATERIALS AND METHODS: To answer the stated
      questions a review of the literature has been undertaken together with interviews
      of the leading experts and laparoscopic working groups in urologic laparoscopy.
      The gathered information has been summarized and focussed with the aim of
      presenting the perspectives of laparoscopy in urology. RESULTS AND DISCUSSION:
      Standardized indications for laparoscopic urological surgery are benign
      nephrectomy, nephroureterectomy, cryptorchidism, adrenalectomy, renal cysts,
      lymphocele and bilateral or relapsing varicocele. Future indications might
      include living donor nephrectomy, partial nephrectomy and cyst decortication for
      adult polycystic kidney disease. Controversy exists about the laparoscopic
      treatment of malignancies in the urinary tract. Whereas pelvic lymph node
      dissection--even if performed with decreasing frequency--is accepted worldwide,
      retroperitoneal lymphadenectomy for low-stage testis cancer is currently
      performed only at few centers. The recent breakthrough in uro-oncological
      laparoscopic surgery has been laparoscopic radical prostatectomy changing our
      views on the limits of laparoscopic urology. Endoscopic suturing devices (i.e.
      Endostitch) are further being developed, and a prototype reapproximating micro
      clips (VCS stapler) has been used to perform a uretero-ureterostomy
      laparoscopically in a porcine model. Nevertheless, the ability of endoscopic
      suturing using the standard equipment has still to be considered as a "conditio
      sine qua non". Improvements for tissue division and dissection include an
      electrosurgical snare to perform a partial nephrectomy, the development of a
      pneumodissector and hydrodissector. Robotics, including the AESOP 3000 and ZEUS
      represent a glimpse of the future. By positioning the optique in a voice
      controlled full range motion mechanic arm, the image on the screen is very steady
      and the ergonomics of the surgeons is increased significantly. The da Vinci
      System, however, is the first system that has translated all visions of
      telepresence surgery into clinical reality, recently also for laparoscopic
      radical prostatectomy. CONCLUSIONS: The future of laparoscopic urology is a two
      tiered approach. On the first tier, the advancement of complex reconstructive and
      ablative surgery such as laparoscopic prostatectomy or, laparoscopic
      retroperitoneal node dissection, will be undertaken by referral centers of
      expertise. It is from these individuals that we will look to in order to separate
      what is feasible and what is reasonable. The second tier will be focusing on
      simplifying the procedure for the average urologist. As such, developments such
      as the pneumodissector, hydrodissection, and hand assistance will bring
      exstirpative laparoscopy into the realm of more urologists. What is critical is
      that the urologic community supports both groups of laparoscopists.

PMID- 11528184
TI  - EAU guidelines on prostate cancer.
AB  - OBJECTIVES: To develop clinical guidelines for the management of patients with
      prostate cancer. METHODS: Guidelines were compiled by a working panel based on
      current literature following a literature review using MEDLINE. Already published
      structured analysis from national and international guidelines was used, and
      panel consensus was employed when literature evidence was absent or of poor
      quality. RESULTS: The full text of the guidelines is available through the EAU
      Central Office and the EAU website (www.uroweb.org). This article summarizes the
      main conclusions from the guidelines concerning the diagnosis and staging,
      treatment and follow-up of patients with prostate cancer. The diagnosis of
      prostate cancer should be based on histopathological or cytological examinations.
      N- and M-staging may be omitted in selected patients with a low serum prostate
      specific antigen due to low risk of metastasis. Active treatment is warranted in
      most stages of prostate cancer but active monitoring is recommended for elderly
      patients with early stage tumours and is still optional in some other situations.
      Follow-up is based on a disease-specific history, serum-prostate-specific antigen
      supplemented by a digital rectal examination. Routine imaging is not necessary in
      asymptomatic patients. CONCLUSIONS: Prostate cancer is one of the most common
      malignancies in men. These guidelines have been drawn up to provide support in
      the management of this large group of patients.

PMID- 11528185
TI  - EAU guidelines on testicular cancer.
AB  - OBJECTIVES: To establish guidelines for the diagnosis, staging, treatment and
      follow-up of germ cell testicular cancer. METHODS: A search of published work was
      conducted using Medline. Highly evidence-based articles were selected and their
      findings analysed by the members of the Oncological Urology Working Group of the
      EAU. Testis cancer is rare and affects young men in their 3rd and 4th decades of
      life. The majority of these tumours are derived from germ cells (seminomatous and
      non-seminoma germ cell testicular cancer), and more than 50% of patients are
      diagnosed with stage I disease. Epidemiological, pathological and clinical risk
      factors are well established. The tumour, node, metastasis (TNM) staging system
      is endorsed, and for metastatic disease a recently devised prognostic-factor
      based staging system has proven to be useful. Staging assessment includes pre-
      and post-orchiectomy marker levels, pathology of the testis, and nodal and
      visceral status. Following orchiectomy, treatment depends on the tumour type,
      pathological risk factors for stage I disease and clinical prognostic factors for
      advanced disease. The cure rate is excellent for disease stages I and II,
      irrespective of the treatment adopted. However, the pattern of relapse (rate,
      timing and site) is highly influenced by therapeutic policy. For metastatic
      disease, survival depends on clinical prognostic factors and treatment. Follow-up
      schedules are tailored according to stage, tumour type and post-orchiectomy
      treatment schedules. CONCLUSIONS: Excellent cure rates are achieved for early
      stage germ cell testis tumours following accurate staging at diagnosis.
      Satisfactory survival rate can be achieved in advanced metastatic disease using a
      multidisciplinary therapeutic approach. Follow-up schedules vary, depending on
      the pathology and stage of the primary tumour and on the treatment policy adopted
      following orchiectomy.

PMID- 11528186
TI  - Radiation-induced haemorrhagic cystitis.
AB  - OBJECTIVES: In this article we review the literature concerning the frequency and
      management of severe haemorrhagic radiation-induced cystitis. METHODS: A Medline
      search was performed from 1966 to 1999 for articles in English. A total of 309
      references were found. Abstracts and complete articles were reviewed. RESULTS:
      Severe haemorrhagic cystitis following radiotherapy remains a relatively rare
      event. However, the fact that it is relentlessly progressive and that treatment
      options are suboptimal makes it clinically important. The incidence of severe
      haematuria following pelvic irradiation is difficult to determine from the
      literature although most studies state an incidence of less than 5% which
      increases with time since irradiation. Methods of treatment include simple
      bladder irrigation, cystodiathermy, oral, parenteral and intravesical agent,
      hyperbaric oxygen therapy, hydrodistension, internal iliac embolisation, urinary
      diversion and cystectomy. No management strategy is 100% successful and a
      stepwise progression in treatment intensity is often required. CONCLUSION: The
      articles available on radiation-induced haemorrhagic cystitis are principally
      retrospective and involve small numbers of patients who have had several
      different treatment modalities. In the absence of randomised studies comparing
      treatments, it is impossible to set definitive rules about management but
      patients with this condition probably warrant early and aggressive treatment.

PMID- 11528187
TI  - Transrectal high intensity focused ultrasound for the treatment of localized
      prostate cancer: factors influencing the outcome.
AB  - OBJECTIVES: Efficacy evaluation of high intensity focused ultrasound (HIFU)
      treatment for localized prostate cancer and identification of the factors
      affecting the outcome. PATIENTS AND METHODS: 102 patients with prostate cancer
      stage T1-T2 and noncandidates for radical prostatectomy have been treated with
      HIFU (Ablatherm, EDAP-Technomed). The disease progression (failure) was strictly
      defined by any positive sample at control biopsies, whatever the prostate
      specific antigen (PSA) level, or by 3 consecutive increases in PSA levels in case
      of negative biopsies. RESULTS: At inclusion, patients' baseline characteristics
      were (mean +/- standard deviation): age 70.8 (+/-6.13) years, PSA 8.38 (+/-4.8)
      ng/ml, prostate volume 33.3 (+/-16.71) cm3. The population mean follow-up was 19
      months (3-76 months). The overall success rate was 66%. Statistically significant
      variations of the overall success with a more favorable outcome were observed
      when (1) the initial PSA level was < or =10 ng/ml (73 vs. 50%, p = 0.02), (2) the
      Gleason score was < or =6 (81 vs. 46%, p<0.001) and (3) the pretreatment sextant
      biopsy evidenced 1-4 positive samples (68 vs. 40%, p = 0.01). CONCLUSION: Results
      observed after HIFU treatment in localized prostate cancer are now challenging
      those obtained after radiation therapy. The success rate is influenced by disease
      related prognostic factors.

PMID- 11528188
TI  - Orchidectomy following failure of antiandrogen monotherapy in patients with
      metastatic prostate cancer.
AB  - OBJECTIVE: Patients with metastatic prostate cancer who are initially treated by
      oral antiandrogens and then have progressive disease may be offered surgical
      castration as a second-line treatment. Twenty-eight such patients were reviewed
      to determine the outcome in terms of secondary PSA response, symptomatic relief
      and disease-specific survival. MATERIALS AND METHODS: Retrospective chart-based
      review of patients undergoing bilateral scrotal orchidectomy after failure of
      antiandrogen monotherapy. RESULTS: Patients who had a >50% reduction in PSA at 12
      weeks' postorchidectomy had significantly greater duration of PSA response and
      disease-specific survival. 64% of patients who had bone pain prior to
      orchidectomy had some relief of symptoms postoperatively. No prognostic
      indicators of improved survival were identified. CONCLUSION: Orchidectomy as a
      secondary hormonal treatment following relapse on antiandrogens does produce a
      response in terms of PSA level and symptoms in some patients.

PMID- 11528189
TI  - Periprostatic local anesthesia before ultrasound-guided prostate biopsy: an
      update of the miami experience.
AB  - INTRODUCTION: Transrectal ultrasound (TRUS)-guided biopsy is a very common office
      procedure for most urologists. Pain or discomfort associated with this procedure
      has been addressed recently by the use of periprostatic local anesthesia. We re
      address this issue with an update of our experience and emphasize the crucial
      steps that contribute to the success of the technique. We also analyzed the
      subsequent intraoperative effects of injecting lidocaine into the area of the
      neurovascular bundles. MATERIALS AND METHODS: Between June 1999 and December
      2000, 200 patients underwent TRUS-guided biopsies of the prostate. Patients were
      properly consented and subjected to the procedure using periprostatic nerve block
      with 10 cm3 of 1% plain lidocaine. An 'ultrasonographic wheal' was created
      between the rectal wall and the posterior aspect of the prostate and three or
      four different locations along the neurovascular bundles. Pain scores were
      evaluated with the visual analogue scale. RESULTS: TRUS biopsy of the prostate
      was performed in 200 consecutive patients using periprostatic local anesthesia,
      40 patients (20%) had undergone previous prostate biopsy without anesthesia. The
      age of patients ranged from 44 to 75 years (mean 67). The number of biopsies
      ranged from 6 to 14. Mean time from introduction of the probe per rectum to the
      end of the procedure was 18 min. There were no instances of clinical infection,
      significant bleeding, urinary retention, diaphoresis or hypotension. The visual
      analogue scale ranged from 1 to 3 (mean 2). Intraoperative findings in 62
      patients who subsequently underwent nerve-sparing radical retropubic
      prostatectomy were no different from the patients who had biopsies without a
      local anesthetic. CONCLUSION: TRUS-guided biopsy of the prostate is the procedure
      of choice for diagnosing prostate cancer. This procedure can be accomplished with
      minimal pain with the use of periprostatic local anesthesia. It is an easy, safe,
      acceptable and reproducible technique that we believe should be considered for
      all patients undergoing TRUS biopsy regardless of age or number of biopsies.

PMID- 11528190
TI  - Perioperative morbidity of the extended radical perineal prostatectomy.
AB  - PURPOSE: Perioperative morbidity is an essential indicator for the quality of an
      operative technique. This fact is especially important in radical prostatectomy
      since different treatment modalities may provide similar outcome in terms of
      local tumor control. MATERIALS AND METHODS: The conventional type of radical
      perineal prostatectomy is associated with a significant percentage of positive
      surgical margins and was therefore substituted by a modified extended radical
      perineal prostatectomy at our institution. This procedure which includes partial
      resection of the dorsal vein complex and extrafascial resection of the seminal
      vesicals was performed in 200 patients with clinical T1 to T3 prostate cancer.
      The medical records were retrospectively reviewed for perioperative morbidity.
      RESULTS: There was no perioperative mortality and only 7% of the patients
      experienced postoperative complications. Blood substitution was indicated in 14%
      of the patients and could be reduced to 4% in the last 50 patients. The
      reintervention rate was 2.5% including 3 patients in whom a rectocutaneous
      fistula had to be repaired. The suction drainage was removed in 92% patients
      within 5 days. The indwelling catheter stayed in place for less than 14 days in
      89% of all patients and was removed as early as after 2-7 days in 92% of the last
      50 patients. Anastomotic strictures were observed in 8 (5%) of 160 patients
      followed for more than 6 months. 87.4% of patients were considered continent
      after at least 6 months follow-up. However, pad use was reported in 33.6%.
      CONCLUSION: The extended type of radical perineal prostatectomy provides
      excellent results in terms of perioperative morbidity, although a significant
      learning curve can be noted, which is indicated by blood substitution and
      duration of necessary catheter drainage. Since the rate of positive surgical
      margins in pT3 tumors is low (21%) and iatrogenic positive margins in pT2 tumors
      are avoided, this type of prostatectomy should be performed in case a potency
      sparing procedure is not indicated.

PMID- 11528191
TI  - Intravesical BCG in patients with carcinoma in situ of the urinary bladder: long
      term results of EORTC GU Group phase II protocol 30861.
AB  - OBJECTIVES: This phase II study was designed to assess the response rate, side
      effects and long-term efficacy of BCG in the treatment of carcinoma in situ (Cis)
      of the urinary bladder. METHODS: 103 eligible patients with Cis were treated with
      6 consecutive weekly intravesical instillations of 120 mg BCG-Connaught. In case
      of no response, a second 6-week course was given. RESULTS: A complete response
      (CR) was observed in 77 of the 103 eligible patients (75%) and 93 evaluable
      patients (83%). In 6 of 10 patients the CR was induced by a second cycle of 6
      weekly instillations. After a median follow-up of 7.6 years, 39 of the 77 CR
      patients (50%) are still alive and have retained their bladder, 31 (40%) without
      tumor recurrence. Another 7 patients underwent cystectomy and are still alive
      while 16 (20%) have died due to bladder cancer. Ten patients stopped treatment
      due to toxicity. In 2 patients, cystectomy was done because of severe cystitis
      and reduced bladder capacity. Drug cystitis, bacterial cystitis and fever
      occurred in 45, 15 and 15% of the patients, respectively. Severe drug cystitis
      was noted in 3 out of 10 patients receiving more than 6 instillations,
      necessitating cystectomy in 1 case. CONCLUSION: Intravesical short-term BCG is an
      effective treatment modality in Cis, yielding a high CR rate. This therapy may
      however be suboptimal in some patients as the 5-year disease-free rate in
      complete responders drops to 60%. Still, this is an acceptable result for
      patients in whom cystectomy would otherwise be performed in virtually all cases.

PMID- 11528192
TI  - Distressful symptoms after radical cystectomy with urinary diversion for urinary
      bladder cancer: a Swedish population-based study.
AB  - OBJECTIVE: To study the excess prevalence of distressful symptoms after radical
      surgery for urinary bladder cancer. METHODS: We included all patients who
      underwent cystectomy due to bladder cancer before 1996 in Stockholm County. A
      control group was randomly selected from the general population. Information was
      collected by means of an anonymous postal questionnaire. RESULTS: Completed
      questionnaires were returned by 310 (71%) controls and 251 (85%) cystectomized
      individuals. A 5-fold (reservoir) and 9-fold (conduit) increase in defecation
      urgency and a 4-fold (reservoir) and 6-fold (conduit) increase in faecal leakage
      were reported in individuals operated on. Urinary tract infection was increased 3
      fold in cystectomized individuals compared with controls, during the previous
      year 26% of the patients reported a symptomatic infection. The perception of a
      reduced physical attractiveness due to disease was more than 5-fold increased in
      the men operated on compared to the controls. The majority, 135 out of 201 (67%),
      reported that they would have refused alternative bladder-sparing procedures if
      they decreased the prospects of survival by even as little as 1%. CONCLUSIONS:
      The patient's situation after cystectomy is considerably impaired due to changed
      bowel and sexual function, urinary tract infections and a sense of decreased
      attractiveness. However, most patients are in spite of this unwilling to
      compromise survival.

PMID- 11528193
TI  - Expression of pS2 protein and its relation with the Ki-67 proliferative indices
      and tumor recurrence in superficial bladder carcinomas.
AB  - OBJECTIVE: To investigate the expression and possible role of pS2 protein as a
      predictor of tumor recurrence in superficial transitional cell carcinoma of the
      bladder and to determine its relation with tumor stage, grade, size, number,
      recurrence and proliferative activity. METHODS: Paraffin sections of
      transurethral resection material from 80 patients with superficial transitional
      cell bladder carcinoma were stained with pS2 and Ki-67 antibodies using the
      standard streptavidin biotin immunoperoxidase method. Cytoplasmic pS2 staining
      was scored on a scale of 1-3 and the Ki-67-labelling index was determined as a
      percentage of positively staining tumor cells. RESULTS: An inverse relationship
      was found between pS2 expression and Ki-67 index (p<0.001). pS2 expression showed
      no relation with any clinicopathological prognostic parameters as well as the
      recurrence rate. The recurrence rate was only associated with increased tumor
      number (p = 0.05), while the time to first recurrence was significantly related
      to tumor size, proliferative activity and tumor grade (p = 0.04, p<0.001, and p =
      0.03, respectively). On the other hand, higher tumor grade was correlated with
      increased tumor number, Ki-67 index and tumor stage (p = 0.016, p = 0.006, and
      p<0.001, respectively). CONCLUSION: pS2 expression is associated with a low
      proliferative potential of superficial transitional cell carcinoma of the
      bladder, while it does not seem to be related to the recurrence rate of the tumor
      and other prognostic factors. Tumor size and proliferative activity may aid in
      the estimation of the time to the first recurrence.

PMID- 11528194
TI  - Prospective evaluation of Ki-67 labeling in predicting the recurrence and
      progression of superficial bladder transitional cell carcinoma.
AB  - PURPOSE: We studied a series of superficial transitional cell carcinoma of the
      bladder to assess whether the Ki-67 labeling index predicts recurrence and
      progression in a cohort of patients treated by transurethral resection alone or
      receiving adjuvant intravesical bacillus Calmette-Guerin therapy (BCG). MATERIALS
      AND METHODS: From 1989 to 1990, we prospectively studied 70 consecutive cases of
      superficial transitional cell carcinoma of the bladder using Ki-67
      immunostaining. The tumors were 43 pTa and 27 pTl. Thirteen were treated with
      transurethral resection only and 57 received adjuvant intravesical BCG. The
      median follow-up times was 64 months. The threshold index values of Ki-67 for
      recurrence and progression were determined using ROC curves. The relative
      predictive values of the Ki-67 labeling index and tumor characteristics for
      recurrence and progression were evaluated using Cox's proportional hazards model.
      RESULTS: A cutoff value of 13% was determined. The recurrence free survival rate
      at 5 years was 68% for cases with a Ki-67 labeling index of 13 or higher and 71%
      for those with an index of less than 13 (NS). The progression-free survival rate
      at 5 years was 43% in cases with an index of 13 or higher and 89% in those with
      an index of less than 13 (p<0.0001). Using multivariate analysis the Ki-67
      labeling index is an independent risk factor for tumor progression with a
      relative risk of 4.61 (p<0.05). CONCLUSION: When BCG is used for high and
      intermediate risk superficial bladder cancers, the Ki-67 labeling index is an
      independent predictive factor of progression but not of recurrence.

PMID- 11528195
TI  - Sildenafil: efficacy and safety in daily clinical experience.
AB  - OBJECTIVES: Sildenafil citrate (Viagra) is a potent selective inhibitor of
      phosphodiesterase type 5 proposed for the oral treatment of erectile dysfunction
      (ED). The aim of this study was to evaluate its efficacy and safety when used in
      daily practice in patients with ED of various aetiology. PATIENTS AND METHODS:
      From September 1998 to April 1999, 380 patients chose sildenafil as treatment for
      their ED. One hundred and forty-five (38%) of them suffered from psychogenic ED,
      125 (33%) organic and 110 (29%) of mixed aetiology. The grade of erection
      achieved and the occurrence of satisfactory sexual intercourse assessed the
      efficacy. Safety and tolerance were evaluated recording any side effect or
      adverse event. RESULTS: The overall efficacy of Viagra was 77%, with a response
      of 100% among the group of hormonal patients, 88% for psychogenic, 72% for mixed,
      69% for diabetes, 65% for vascular and 60% for neurological symptoms. A few and
      mild to moderate side effects were recorded. CONCLUSION: These results indicate
      that the use of sildenafil citrate is an effective and well-tolerated therapy for
      men with ED of various aetiology with an overall success rate of 77%.

PMID- 11528196
TI  - Vardenafil increases penile rigidity and tumescence in men with erectile
      dysfunction after a single oral dose.
AB  - OBJECTIVES: To evaluate the effect of two doses of vardenafil hydrochloride on
      penile rigidity and tumescence while determining the pharmacokinetics. METHODS:
      Twenty-one patients with erectile dysfunction completed three oral single-dose
      regimens (placebo, 20 and 40 mg vardenafil) in a randomized, placebo-controlled,
      3-way cross-over study. Penile rigidity and tumescence were measured at the base
      and tip with a Rigiscan for up to 2 h after dosing. The period included three 20
      min repeated episodes of visual sexual stimulation. Blood samples were taken
      periodically up to 24 h after dosing. RESULTS: After 20 and 40 mg vardenafil, the
      mean duration of >60% rigidity of the base of the penis was greater than after
      placebo by 42.9 min (95% Cl 29.3-56.4) and by 49.3 min (95% Cl 35.7-62.9),
      respectively (p<0.001), and greater than after placebo by 34.6 min (95% Cl 22.1
      47.1) for both doses at the tip. Additionally, significantly greater rigidity
      activity units and tumescence activity units were found for both doses compared
      with placebo (p<0.001). The plasma concentrations of vardenafil increased
      rapidly, with a median t(max) of about 40 min and a mean t1/2 of 4.4-4.8 h.
      Relative bioavailability was slightly higher for the 40-mg dose than for the 20
      mg dose. The treatments were well tolerated, although slightly more adverse
      events, primarily headache, flushing and nasal congestion, were seen with the 40
      mg dose compared with placebo. CONCLUSION: The findings confirm that vardenafil
      was able to generate stronger erections of longer duration than placebo under
      conditions of visual sexual stimulation in patients with erectile dysfunction.
      The pharmacokinetic, pharmacodynamic and tolerability profiles support vardenafil
      hydrochloride as a strong candidate for further testing as a treatment for
      erectile dysfunction.

PMID- 11528197
TI  - Voiding dysfunction of sigmoid neobladder in women: a comparative study with men.
AB  - OBJECTIVE: We compared results of urodynamic testing in male and female patients
      with sigmoid neobladders following radical cystectomy to determine factors
      important to voiding status, especially in women. METHODS: Continence status,
      urodynamics by pressure-flow measurements, and neocystograms were evaluated in 14
      male and 9 female patients. RESULTS: Of 14 male patients, 11 (78.6%) showed
      acceptable urinary continence during the day, as did all of the 9 female
      patients. At night, 6 of the 14 men and 6 of the 9 women were continent with or
      without voiding at regular intervals. All 14 male patients could void
      volitionally during the follow-up period. In contrast, 1 of 9 female patients
      required clean intermittent catheterization to manage the large amount of
      residual urine. Her neocystourethral angle was 90 degrees and pelvic descent of
      the bladder (pouchocele) was observed. The intrareservoir pressure at maximal
      flow was significantly lower in female than in male patients (p<0.05). The ratio
      of abdominal pressure to intrareservoir pressure did not differ significantly
      between males and females. Abdominal straining generated most of the
      intrareservoir pressure. An increase in intrareservoir pressure was associated
      with urinary flow, but the magnitude of pressure did not correlate with the peak
      urinary flow. CONCLUSION: The location of the neobladder and avoidance of
      angulation at its outlet are important for obtaining good voiding after the
      reconstruction of neobladder in women, but the intrareservoir pressure is less
      critical.

PMID- 11528198
TI  - A conservative treatment of phimosis in boys.
AB  - OBJECTIVE: The aim of this study was to evaluate the efficacy of topical
      applications of clobetasol propionate cream in the treatment of phimosis in boys
      and a comparison of the results presented with an overview of the current
      studies. METHODS: In a prospective study, 94 boys (mean age 5.5 years) were
      treated with topical applications of 0.05% clobetasol propionate cream twice
      daily. The prepuce was treated for 1 month, with an attempt at prepuce retraction
      after 14 days. The boys were evaluated after 1 month of treatment and every 3
      months during follow-up. RESULTS: Of the 94 boys, 91 were available for follow
      up, of whom 42 boys (46.1%) achieved complete retraction of the prepuce, 24
      (26.4%) had only preputial adhesions and 4 (4.4%) had partial retraction. Twenty
      one boys (23.1%) had no response. The treatment was continued in 13 boys with
      good results eventually. Seven boys (7.7%) had recurrence after a mean follow-up
      of 4.3 months (range 2-7). No side effects were noted. Circumcision was necessary
      in 24 of the 91 boys (26.4%). The mean follow-up was 11.0 months (range 3-18).
      CONCLUSIONS: Local application of clobetasol propionate cream is a simple, safe
      and effective treatment for phimosis in boys and avoids circumcision and its
      associated risks. It should be offered first instead of circumcision.

PMID- 11528199
TI  - Prospective randomized trial using laser acupuncture versus desmopressin in the
      treatment of nocturnal enuresis.
AB  - OBJECTIVES: Several treatment modalities for children suffering from
      monosymptomatic nocturnal enuresis are available, but desmopressin is a well
      established option. On the other hand, alternative nonpharmacological therapies
      such as laser acupuncture are more frequently requested by the parents. To our
      knowledge, there is no prospective randomized trial which evaluated the efficacy
      of such an alternative approach in comparison with the widespread use of
      desmopressin. METHODS: Forty children aged over 5 years presenting with primary
      nocturnal enuresis underwent a previous evaluation of their voiding function to
      assure normal voiding patterns and a high nighttime urine production. Then the
      children were randomized into two groups: group A children were treated with
      desmopressin alone, and group B children underwent laser acupuncture. All
      children were investigated after a minimum follow-up period of 6 month to
      evaluate the duration of the response. RESULTS: The children of both groups had
      an initial mean frequency of 5.5 wet nights per week. After a minimum follow-up
      period of 6 months reevaluation revealed a complete success rate of 75% in the
      desmopressin-treated group. Additional 10% of the children had a reduction of
      their wet nights of more than 50%. On the other hand, 6 months after laser
      acupuncture, 65% of the randomized children were completely dry. Another 10% had
      a reduction of the enuresis frequency of more than 50% per week. 20% of the
      children in the desmopressin-treated group did not respond at all as compared
      with 15% in the acupuncture-treated group. Statistical evaluation revealed no
      significant differences among the response rates in both groups. CONCLUSION: Im
      comparison with pharmacological therapy using desmopressin, our study shows that
      laser acupuncture should be taken into account as an alternative, noninvasive,
      painless, cost-effective, and short-term therapy for children with primary
      nocturnal enuresis in case of a normal bladder function and high nighttime urine
      production. Success rates indicated no statistically significant differences
      between the well-established desmopressin therapy and the alternative laser
      acupuncture.

PMID- 11528200
TI  - Association of smoking with urgency in older people.
AB  - OBJECTIVE: To evaluate the association of smoking with urgency in older people.
      METHODS: A population-based survey involving 1,059 people aged 60-89 years. A
      stratified sampling method was used and data were collected by interviews. The
      response rate was 82%. The indicators were urgency, former and current smoking,
      alcohol and coffee drinking. Prevalences of urgency were calculated for 15-year
      age groups of the two genders. Logistic regression models were used to analyse
      the age-adjusted association of urgency with smoking, use of alcohol and coffee
      drinking in the whole study population and separately in the two gender groups.
      RESULTS: The prevalence of urgency was lowest among younger men (6.6%) and
      highest among older women (19.5%). In the whole study population including both
      genders the current smokers were at greater risk of suffering from urgency [OR
      (odds ratio) 2.76; 95% CI (confidence interval) 1.43-5.32] than the never-smokers
      while the OR of urgency for former smokers was 1.63 (95% CI 0.97-2.74). In the
      separate models for the two genders the current male smokers (OR 2.55; 95% CI
      1.13-5.73) and the former female smokers (OR 2.62; 95% CI 1.14-6.0) were at
      greater risk. The OR for current female smokers was 2.54 (95% CI 0.79-8.22), but
      the group was very small. Alcohol use and coffee drinking were not associated
      with urgency. CONCLUSION: Smoking is associated with urgency in older people.
      Especially current smokers are at greater risk than never-smokers. The prevalence
      of urgency is higher among women and is increased in both genders with advancing
      age. The study material being cross-sectional the causal relationship cannot be
      confirmed.

PMID- 11528201
TI  - A comparative cross-sectional study of lower urinary tract symptoms in both
      sexes.
AB  - OBJECTIVES: The aims of this investigation were to compare prevalence and
      severity of lower urinary tract symptoms (LUTS) in both sexes and to analyze
      their effect on everyday life ('botherness') in a cross-sectional study design.
      METHODS: Individuals participating in a health survey in Vienna completed a
      German version of the Bristol LUTS questionnaire. In this questionnaire, storage
      (irritative) and voiding (obstructive) symptoms were assessed by six items, each
      followed by a quality of life ('botherness') question. RESULTS: A consecutive
      series of 1,191 women (49.8+/-13.5 years) and 1,211 men (48.5+/-11.9 years) were
      analyzed. The mean increase in LUTS from the youngest (20-39 years) to the oldest
      (>70 years) age group was 43.7% (7.3%/decade) for men and 23.6% (3.9%/decade) for
      women. In all decades, storage symptoms were higher for women. Beyond the age of
      60 years this discrepancy declined. Voiding symptoms were almost identical in
      both sexes until the 5th decade, thereafter they increased significantly in men
      but not in women. 'Urgency' and 'frequency' were more bothersome to older
      individuals, 'nocturia' and voiding symptoms were almost equally bothersome to
      younger and older participants. CONCLUSIONS: These data provide insights into the
      development of storage and voiding problems with age in both sexes. Sex- and age
      stratified analyses of quality of life impairments ('botherness') due to LUTS
      have demonstrated the importance of age for the impact of LUTS on the bother
      score.

PMID- 11528202
TI  - Methods for measuring crystallization in urolithiasis research: why, how and
      when?
AB  - Whereas crystalluria does not distinguish between kidney stone formers and
      healthy people and thus can be considered a physiologic event, kidney stone
      formation is a pathologic incident and reflects a specific form of
      biomineralization. Both single urinary crystals as well as whole kidney stones
      form under exquisite control of organic macromolecules. Simple crystal formation
      in the urinary tract is distinguished from stone formation in the kidney by the
      process of particle retention. The latter occurs either because nucleated
      crystals strongly aggregate to particles too large to pass freely through the
      tubules ('free particle' theory), or because crystals become abnormally adherent
      to tubular cell surfaces ('fixed particle' theory). Since it is impossible to
      mimic all the processes involved in stone formation in vitro, it is highly
      important to carefully chose a specific crystallization process for in vitro
      studies, and to select the most appropriate experimental conditions for measuring
      the chosen process as reliably as possible. This overview aims at critically
      reviewing the principles of currently available assay systems for studying
      crystallization processes involved in stone formation. Consensus is reached by
      the experts that no in vitro system really mimics what happens in renal stone
      formation, but that carefully designed in vitro studies will always play an
      important part in urolithiasis research. For such studies, it is highly important
      to exactly control the appropriate experimental conditions that are relevant to a
      specific crystallization process under investigation. Practical guidelines for
      researchers working with crystallization systems are provided, and it is
      concluded that international efforts should be made to standardize the
      terminology, to agree on a set of basic experimental parameters (temperature, pH,
      artificial urine composition), and to adopt simple tests or conditions are
      reference points for quality and comparative control.

PMID- 11528203
TI  - High-throughput microarray technologies: from genomics to clinics.
AB  - BACKGROUND: Despite continuous research efforts in the past decades, there are
      still cancers where no effective treatment is available, such as advanced kidney
      cancer or hormone-refractory prostate cancer. A better understanding of the
      molecular mechanisms of cancer development and progression is the basis for the
      development of new diagnostic and therapeutic strategies. Current developments in
      genomics have a dramatic impact on the whole field of research. The sequence of
      the entire human genome will soon be fully sequenced and provide the 'book of
      life' as a basis for the understanding of human disease. METHODS AND RESULTS: New
      technologies have emerged to translate the human genome sequence into gene
      function and improved diagnostics or treatment modalities. New technologies such
      as microarrays are not only important for fundamental research, but will also be
      useful for diagnostic, prognostic or therapeutic purposes in individual patients.
      DNA microarrays make it possible to analyze the mRNA expression of thousands of
      genes simultaneously. The resulting comprehensive gene expression surveys lead to
      the identification of new genes and pathways with importance in cancer
      development and progression, or as targets for new therapies. The validation and
      prioritization of genes emerging from genome screening analyses in large series
      of clinical tumors has become a new bottleneck in research. Therefore, we have
      recently developed the tissue microarray (TMA) technology to efficiently test the
      clinical relevance of candidate genes. TMAs are microscope slides containing
      samples from hundreds of individual tumor specimens. They can be used for large
      scale, massively parallel in situ analysis of genetic alterations on a DNA, RNA
      and protein level using in situ hybridization or immunohistochemistry on hundreds
      of tumor specimens at a time. Microarray technologies are already increasingly
      being used in urologic research, and will also have a strong impact on clinical
      urology. CONCLUSIONS: DNA microarrays and TMAs provide a powerful approach to
      identify large numbers of new candidate genes, and rapidly validate their
      clinical impact in large series of human tumors. These technologies will soon
      lead to a better molecular understanding of urologic tumors, and accelerate the
      identification of new prognostic markers or therapeutic targets.

PMID- 11528204
TI  - Discrepancy between Gleason scores of biopsy and radical prostatectomy specimens.

PMID- 11528206
TI  - Influences of the N- and C-termini of the distal nephron inward rectifier, ROMK.
AB  - The inward rectifying potassium channels of the ROMK family are present in the
      distal nephron of the kidney. These channels have two membrane spanning portions,
      between which lies a hydrophobic domain thought to confer the majority of the
      conductive properties of the channel. The N- and C-termini are both
      intracellular. In this paper we have examined the contribution of the N- and C
      termini to the pore by examining the interaction of Cs+ with the channels. ROMK1
      has an additional 19 amino acids on its N-terminus in comparison to ROMK2. The C
      terminus of ROMK2 was extended by addition of a streptavidin tag (sfROMK2).
      Currents were measured following expression in Xenopus oocytes using two
      electrode voltage clamp. ROMK1, ROMK2 and sfROMK2 exhibited concentration- and
      voltage-dependent block of inward currents by extracellular Cs+. The Hill
      coefficients were not significantly different from one. The mean Kd values at 0
      mV were 100.6 +/- 10.6, 63.1 +/- 3.9 and 40.6 +/- 9.4, respectively (p < 0.05).
      The electric distances (delta) were 0.94 +/- 0.06, 1.0 +/- 0.05 and 1.37 +/- 0.06
      respectively. The delta of sfROMK2 was greater than either ROMK1 or ROMK2 (p <
      0.001). ROMK1, ROMK2 and sfROMK2 are sensitive to extracellular Cs+. Block was
      both concentration- and voltage-dependent. sfROMK2 is most Cs+-sensitive. ROMK1
      contains an additional N-terminal 19 amino acids. Thus the pore properties of
      these two isoforms are subtly different, and influenced by the N-terminus. The
      lower Kd in sfROMK2 suggests that the streptavidin tag, and perhaps the C
      terminus, also affect the pore.

PMID- 11528207
TI  - Hippurate metabolism as a hydroxyl radical trapping mechanism in the rat kidney.
AB  - Hippurate (Hip) is considered to be the end product of benzoate (BA) metabolism.
      However, the kidney is able to metabolize Hip. Although only Hip but no BA is
      present in the blood, rat urine contains under normal conditions less Hip (about
      0.4 mM) than BA (about 4.5 mM) and of hydroxylated derivatives of BA (hydroxy-BAs
      = HB and dihydroxy-BAs = DHB). Generation of HBs and DHBs is the result of
      radical substitution by free OH radicals (*OH). Thus, rate of synthesis of HBs
      and DHBs may reflect the production rate of *OH in the kidney *OH generation is
      elevated following ischemic stress. Therefore, production of HBs and DHBs can be
      expected to be elevated in postischemic injury. The validity of this assumption
      was tested in vitro on isolated tubular segments and in vivo in the rat.
      Metabolism of Hip at 0.1 mmol x l(-1 ) (0.1 mM) as well as of BA resulted in
      enlarged production of both HBs (especially 3-HB and 4-HB) and of DHBs
      (especially 2,6-DHB). Production of 2,3- and especially of 2,5-DHB was elevated
      in the presence of high concentration (1.0 mM) of salicylate (2-HB) only. In vivo
      both in acute (120 min) and in chronic (5 days) experiments ligation of one renal
      artery for 30 respectively 60 min resulted in enlarged excretion of HBs and DHBs,
      especially of 2,6- and 3,5-DHB. This finding is noteworthy since (a) formation of
      2,6-DHB necessitates as precursor salicylate which could not be detected in our
      experiments and (b) the spontaneous attack of *OH upon the benzol ring would
      prefer the positions 2,3- 2,5- and 3,4-. Therefore, the existence of regulating
      factor(s) guiding OH groups to definite positions is a distinct possibility.
      These results indicate that metabolism of Hip leading to hydroxylated BAs may be
      a renoprotective mechanism against attack of *OH in reoxygenated renal tissue.

PMID- 11528208
TI  - Effects of sex hormones on Na+/glucose cotransporter of renal proximal tubular
      cells following oxidant injury.
AB  - It was reported that reactive oxygen metabolites play an important role in the
      pathogenesis of several renal diseases including glomerulonephritis, ischemia and
      acute tubular necrosis. However, the effect of oxidants and protective effect of
      sex steroid hormones on Na+/glucose cotransporter of renal proximal tubular cells
      is not yet elucidated. In the present study, we examined the effect of sex
      steroid hormones against tert-butyl hydroperoxide (t-BHP)-induced alteration of
      Na+/glucose cotransporter activity in primary cultured rabbit renal proximal
      tubule cells (PTCs). t-BHP inhibited alpha-methyl-D-glucopyranoside (alpha-MG)
      uptake in a dose-dependent manner. t-BHP-induced inhibition of alpha-MG uptake
      was due not to Km but to the decrease of Vmax. 0.5 mM t-BHP-induced inhibition of
      alpha-MG uptake was significantly blocked by estradiol-17beta, but not by
      progesterone and testosterone. This protective effect was not blocked by estrogen
      receptor antagonist or transcription and translation inhibitor. In addition, 0.5
      mM t-BHP increased [3H]-arachidonic acid (AA) release and Ca2+ uptake. These
      effects of t-BHP were also significantly blocked by estradiol-17beta, but not by
      progesterone and testosterone. Protective efficacy of estradiol-17beta on t-BHP
      induced inhibition of alpha-MG uptake is exhibited between antioxidants and iron
      chelators. In conclusion, estradiol-17beta, but not progesterone and
      testosterone, partially prevented t-BHP-induced inhibition of alpha-MG uptake
      through its antioxidant activity dependent upon phenol structures and inhibition
      of AA release and Ca2+ influx.

PMID- 11528209
TI  - Intrarenal distribution of blood flow in sodium depleted and sodium loaded rats:
      role of nitric oxide.
AB  - The renal hemodynamic effects of nitric oxide synthase (NOS) inhibition and
      dietary salt were studied in rats. L-NAME (0.1 mg/ml in the drinking fluid, about
      12 mg/kg/day) was given for 4 days to rats receiving low (sodium depletion, SD),
      normal (N) or high (sodium load, SL) NaCl diet. Intrarenal hemodynamics was
      studied in anaesthesia. NOS inhibition decreased renal blood flow and increased
      renal vascular resistance in each group. Cortical and outer medullary but not
      inner medullary blood flow increased in direct ratio to the sodium intake. NOS
      inhibition decreased the blood flow and increased the vascular resistance in all
      layers of the kidney in SD, N, and SL rats as well. In SD and N, but not in SL
      rats L-NAME induced vasoconstriction was higher in the outer (OM) and inner
      medulla (IM) than in the cortex (C) [SD: DeltaCVR 43%, DeltaOMVR 54%, DeltaIMVR
      84%; N: DeltaCVR 54%, DeltaOMVR 96%, DeltaIMVR 106%; SL: DeltaCVR 50%, DeltaOMVR
      64%, DeltaIMVR 35%]; in normal rats blood flow shifts from the medulla toward the
      cortex. In conclusion, nitric oxide may have a role in the regulation of renal
      vascular tone not only in the case of regular sodium uptake but in the sodium
      depleted or loaded organism as well. However, nitric oxide has no role in the
      dietary salt evoked vascular adaptation in the kidney.

PMID- 11528210
TI  - Renal hemodynamics in young and old spontaneously hypertensive rats during
      intrarenal infusion of arginine vasopressin.
AB  - BACKGROUND/AIMS: To gain insight into the effect of arginine vasopressin (AVP) on
      renal hemodynamics in hypertensive rats, we investigated the vasoconstrictive
      response to AVP on total renal blood flow (RBF) and total and zonal glomerular
      filtration rate (GFR) in young and old spontaneously hypertensive rats (SHR). A
      hypothesis of increased AVP sensitivity in the juxtamedullary cortex of SHR was
      tested. METHODS: Total RBF and total and zonal GFR were studied in 10- and 40
      week-old SHR and normotensive Wistar-Kyoto rats (WKY). RBF was recorded by a
      flowmeter before infusion of AVP and immediately after injection of a bolus dose
      of 10 ng AVP. Whole kidney GFR and its intracortical distribution was measured by
      the tubular uptake of 125I- and 131I-labelled aprotinin before and during a
      continuous infusion of AVP 5 ng/min. Ligand binding measurements of preglomerular
      V1a receptors were performed in young and old rats. RESULTS: RBF decreased by 43
      +/- 3% in 10-week SHR (9.2 +/- 0.5 vs. 5.2 +/- 0.3 ml x min(-1) x g(-1)),
      significantly more than 10-week WKY where RBF decreased by 35 +/- 3% (9.6 +/- 0.7
      vs. 6.5 +/- 0.5 ml x min(-1) x g(-1)) (p < 0.05). The effect of AVP on RBF was
      attenuated in 40-week-old rats where the decline in RBF was 29 +/- 5% in SHR and
      23 +/- 4% in WKY (p > 0.05). GFR decreased by 6 +/- 3% (1.03 +/- 0.04 vs. 0.96 +/
      0.04 ml x min(-1) x g(-1), p < 0.05) in 10-week SHR and was unchanged in 10-week
      WKY (1.10 +/- 0.07 vs. 1.08 +/- 0.04 ml x min(-1) x g(-1), p > 0.10). GFR
      decreased by 11 +/- 10% in 40-week SHR and by 4 +/- 4% in 40-week WKY (p > 0.05).
      AVP infusion significantly increased filtration fraction in all groups except 40
      week SHR, indicating that AVP has the strongest vasoconstrictive effect on
      postglomerular vessels. The intrarenal distribution of GFR was unchanged in the
      normotensive and hypertensive groups. V1a receptor density was upregulated in
      young SHR compared to young WKY (p < 0.05), but downregulated in old compared to
      young SHR (p = 0.05). CONCLUSION: The results indicate that AVP sensitivity is
      not increased in the juxtamedullary cortex in SHR and the reduced
      vasoconstrictive effect in old SHR is due to a reduced density of V1a receptors.

PMID- 11528211
TI  - Effects of angiotensin II on the renal antioxidant activities of borderline
      hypertensive rats.
AB  - This study was aimed to study the angiotensin II (Ang II)-induced antioxidant
      changes in the kidney of borderline-hypertensive rats (BHR). We measured renal
      antioxidant enzyme activities, and glutathione (GSH) contents and lipid peroxide
      levels in relation to the age of subjects. In the antioxidant enzyme assays,
      consistent changes were not observed in relation to age. However, in the assay
      for reduced GSH, nonenzymatic antioxidant, contents of adult and aged rats were
      much greater than those of weanling rats. Subcutaneous injection of pressor dose
      of human Ang II (200 microg/kg over 90 min) significantly reduced enzymatic
      activities in the weanling (4-week-aged) and adult (10-week-aged) BHR. However,
      in the relatively aged (16-week-aged) rats, Ang II did not alter enzymatic
      activities. Renal GSH contents of aged BHR, were highly increased by Ang II.
      Renal lipid peroxide levels of weanling and adult BHR were increased by Ang II,
      but decreased in the aged rats. However, these characteristic changes of renal
      antioxidant due to Ang II of the BHR could not be observed in the age-matched
      control, Wistar-Kyoto rats (WKR). From these results, it can be concluded that
      impacts of oxidative stress on the kidney of BHR may be greater in the young
      rats.

PMID- 11528212
TI  - Modulation of endothelin-1-induced cytosolic free calcium mobilization and
      mitogen-activated protein kinase activation by erythropoietin in vascular smooth
      muscle cells.
AB  - BACKGROUND: It has been reported that human recombinant erythropoietin (rHuEPO)
      modulates the sensitivity of the cardiovascular system to vasoconstrictors. We
      investigated whether rHuEPO has modulative effects on the endothelin-1 (ET-1)
      induced elevation of cytosolic free calcium concentration ([Ca2+]i) and mitogen
      activated protein (MAP) kinase activation in vascular smooth muscle cells (VSMC).
      METHODS: [Ca2+]i was measured by fura-2/AM, and MAP kinase activation was
      analyzed by Western blotting. RESULTS: Exposure of VSMC to rHuEPO prior to
      stimulation with ET-1 enhanced both basal and ET-1-induced elevation of [Ca2+]i
      in a dose-dependent manner in the presence of extracellular Ca2+. The synergistic
      effect was also retained in the absence of extracellular Ca2+ after exposure to
      rHuEPO. However, the effect was diminished in the presence of extracellular Ca2+
      combined with the intracellular Ca2+ release inhibitor TMB-8, PKC inhibitor, or
      PKC depletion. Exposure to rHuEPO also had a synergistic effect on the activation
      of MAP kinase induced by ET-1; however, this effect was diminished in the
      presence of the Ca2+ chelator BAPTA-AM. CONCLUSION: The results suggest that
      rHuEPO has synergistic effects on ET-1-induced [Ca2+]i mobilization, particularly
      on intracellular Ca2+ release, and MAP kinase activation in VSMC.

PMID- 11528213
TI  - Lack of association between Gly460Trp polymorphism of alpha-adducin gene and salt
      sensitivity of blood pressure in Polish hypertensives.
AB  - BACKGROUND: Previous studies have suggested that alpha-adducin (alpha-ADD)
      polymorphism may identify patients with a salt-sensitive form of hypertension.
      AIM: To investigate the association between Gly460Trp polymorphism of alpha-ADD
      and the pattern of blood pressure response to subacute (1 week) salt loading and
      depletion in young adult thin Polish hypertensives. METHODS: The study group
      consisted of 44 subjects with salt-sensitive hypertension (SS) and 24 subjects
      with non-salt-sensitive hypertension (SR). Genomic DNA isolated from peripheral
      blood leukocytes was amplified by PCR method with primers flanking the
      polymorphic region. The mismatch near to 3'-end of the upstream primer was
      introduced to create a Nla III restriction site in Trp 460 allele. In addition,
      excreted fraction of filtered sodium (FENa), plasma renin activity (PRA) and
      plasma concentrations of aldosterone (ALDO) were determined on normal, low and
      high salt diets. RESULTS: FENa on normal or high salt diets were significantly
      lower in the SS hypertensives as compared with the SR patients. PRA in SS group
      was also significantly lower as compared with results in SR group, but only on
      high salt diet. No significant difference was detected in frequencies of
      genotypes and alleles of alpha-ADD gene between SS and SR subjects. An additional
      analysis with regard to genotype (Gly/Gly vs. Gly/Trp+Trp/Trp) showed no
      significant difference in changes of blood pressure as well as in results of
      laboratory investigations. CONCLUSION: Our results suggest lack of association
      between Gly460Trp polymorphism of alpha-adducin gene and salt sensitivity of
      blood pressure in Polish hypertensives.

PMID- 11528214
TI  - Transjugular renal biopsy. Our experience with 67 cases.
AB  - BACKGROUND: Transjugular renal biopsy (TJRB) is still a novel technique of renal
      tissue sampling exploiting the transjugular route. TJRB should be performed
      particularly in situations when the percutaneous route is precluded, i.e.
      especially in patients with clotting disorders. In the past, only a few papers
      reported the experience with larger numbers of patients. The goal of this paper
      is to analyze our experience with TJRB. METHODS AND RESULTS: From 1993 to 1999,
      67 patients, mean age 49.8 years (SD +/- 10.2), male/female ratio 40/27,
      underwent TJRB. Fifty-two patients (78%) suffered from renal insufficiency and 19
      of them (28%) were on dialysis treatment at the time of TJRB. Arterial
      hypertension was recorded in 42%. The combined kidney and liver biopsy (46%) and
      clotting disorders (39%) were the most frequent indications for performing TJRB.
      Renal tissue was yielded in 53 patients (79%) but a sample sufficient for
      histological diagnosis was taken in 49 (73%), reaching on average 10.8 glomeruli.
      Altogether 19 different histological entities were disclosed and out of them,
      vascular nephrosclerosis (12%), necrotizing and crescentic glomerulonephritis,
      IgA nephropathy (IgAN) and amyloidosis (three latter per 10%) represented the
      most frequent diagnoses. TJRB was combined with liver biopsy in 31 patients (46%)
      and/or hepatic vein catheterization in 22 patients (33%) confirming portal
      hypertension in 8. The clinically significant liver histology was found in 20
      patients, of them cirrhosis/fibrosis in 8, chronic hepatitis in 4 and steatosis
      in 5. Among those 20 patients, IgAN was disclosed as the most common renal
      diagnosis (6). Clinically symptomatic complications were recorded in 12 cases
      (18%) but 9 of them suffered from clotting disorders. Complications included
      development of subcapsular hematoma in 6 cases, macroscopic hematuria in 4 cases,
      and hypovolemic hemorrhagic shock in 2. One patient had to undergo surgical
      treatment. Dividing the patients into a subgroup with or without clotting
      disorders, the complication rate was 34 vs. 7%. CONCLUSIONS: TJRB is a new
      diagnostic method, which, looking at its indications, facilitates the diagnosis
      of glomerulopathies in patients who could not be considered for percutaneous
      renal biopsy, particularly due to clotting disorders. The technical aspect of
      this procedure plays a fundamental role in the final risk/benefit ratio but if
      done correctly it involves acceptable risk and is well tolerated.

PMID- 11528215
TI  - A role of ghrelin in neuroendocrine and behavioral responses to stress in mice.
AB  - Ghrelin, an endogenous ligand of the growth hormone secretagogue receptor, was
      recently identified in the rat stomach. Previous studies have shown that ghrelin
      potently increases growth hormone release and food intake. We examined the
      effects of the gastric peptide ghrelin on anxiety-like behavior in association
      with the hypothalamic-pituitary-adrenal axis in mice. Both intra-third
      cerebroventricular and intraperitoneal administration of ghrelin potently and
      significantly induced anxiogenic activities in the elevated plus maze test.
      Ghrelin gene expression in the stomach was increased by tail pinch stress as well
      as by starvation stress. Administration of a corticotropin-releasing hormone
      (CRH) receptor antagonist significantly inhibited ghrelin-induced anxiogenic
      effects. Peripherally administered ghrelin significantly increased CRH mRNA, but
      not urocortin mRNA expression in the hypothalamus. Furthermore, intraperitoneal
      injection of ghrelin produced a significant dose- dependent increase in serum
      corticosterone levels. These findings suggest that ghrelin may have a role in
      mediating neuroendocrine and behavioral responses to stressors and that the
      stomach could play an important role, not only in the regulation of appetite, but
      also in the regulation of anxiety.

PMID- 11528216
TI  - Immobilization stress rapidly and differentially modulates BDNF and TrkB mRNA
      expression in the pituitary gland of adult male rats.
AB  - Brain-derived neurotrophic factor (BDNF) is a neurotrophin involved in neuronal
      survival and plasticity that binds to high-affinity receptors named TrkB. In the
      central nervous system, brain insults, including stress, induce modifications in
      BDNF messenger RNA (mRNA) expression. The present study attempted to determine in
      the adult rat pituitary, a peripheral structure relevant for the stress response:
      (1) whether BDNF and TrkB mRNA expression is influenced by different durations
      (15, 30, 60, 180 and 300 min) of single immobilization stress; (2) the expression
      of BDNF transcripts containing the different exons and their possible variations
      after stress exposure. Plasma corticotropin (ACTH) and corticosterone
      concentrations were strongly and significantly increased as early as 5 min after
      the stress stimulus. Using RNAse protection assay and in situ hybridization, a
      rapid increase in BDNF mRNA occurred at 15 min. This was accompanied by an
      increase in BDNF protein at 60 min, and by a rapid and significant decrease in
      TrkB mRNA expression observed at 15 and 30 min after stress application. RT-PCR
      analysis of BNDF transcripts showed strong basal expression of exons III and IV,
      whereas transcripts containing exons I and II seemed weakly expressed. After
      stress application, transcripts containing exons III and IV were rapidly and
      significantly increased at 30 min, whereas transcripts containing exons I and II
      remained unchanged. These results show that pituitary BDNF transcripts expression
      is differentially affected by immobilization stress.

PMID- 11528217
TI  - Acute effects of purified and UV-inactivated Herpes simplex virus type 1 on the
      hypothalamo-pituitary-adrenocortical axis.
AB  - Herpes simplex virus type 1 (HSV-1) is a common cause of viral encephalitis,
      manifested by neuroendocrine and behavioral changes. We have previously
      demonstrated that HSV-1 induces marked hypothalamo-pituitary-adrenocortical (HPA)
      axis activation. In this study we characterized the acute effects of HSV-1 on the
      HPA axis occurring before viral replication and appearance of clinical signs of
      encephalitis. Since in previous studies we used crude virus preparations which
      may contain immune factors produced by the infected cells, we tested here the
      effects of purified HSV-1 virions. HSV-1 was propagated on Vero cells and virions
      were purified by centrifugation in sucrose gradients. Inactivation of viral
      infectivity was achieved by UV-irradiation, which caused a million-fold decrease
      in virus titer, as determined by plaque assay. Intracerebroventricular (ICV)
      inoculation of crude or purified virions induced a dose dependent increase in
      serum corticosterone and corticotropin (ACTH). This effect was maximal within 3.5
      h postinfection and lasted for 72 h. ICV inoculation of UV-inactivated purified
      virions caused a marked increase in serum corticosterone and ACTH at 3.5 h, but
      in contrast to the effect of the active virus, the hormone levels gradually
      decreased at 24 h, and returned to basal levels at 72 h postinfection. HSV-1
      induced HPA axis activation at 3.5 h was completely abolished by pretreatment
      with interleukin-1 receptor antagonist, injected ICV. Adrenalectomized rats
      failed to respond to ICV inoculation of purified HSV-1 by increase in ACTH. In
      contrast, these rats responded to ICV injection of LPS. IN CONCLUSION: (1) HSV-1
      can acutely activate the HPA axis before and independently of any viral
      replication; (2) HSV-1-induced HPA axis activation depends on a permissive action
      of circulating glucocorticoids and on host derived brain interleukin-1.

PMID- 11528218
TI  - Acute stress-induced facilitation of the hypothalamic-pituitary-adrenal axis:
      evidence for the roles of stressor duration and serotonin.
AB  - Stress-induced activation of the hypothalamic-pituitary-adrenal (HPA) axis
      stimulates the release of both facilitatory and inhibitory components. We
      proposed that the transient removal of the inhibitory component, corticosterone,
      during a stressor would leave the HPA axis in a state of hyper-responsiveness
      (facilitated state). Consistent with this expectation, we have previously
      observed that aminoglutethimide (AG)-induced removal of corticosterone during an
      immobilization stressor resulted in the hypersecretion of both ACTH and
      corticosterone to a subsequent stressor. In the present study we determined the
      effect of stressor duration on the magnitude of facilitation. AG plus a 10-min
      immobilization (IMM(10)) stress on day 1 resulted in facilitation of the HPA
      axis. This was reflected in higher ACTH and corticosterone responses to an
      injection stress on day 2 as compared to appropriate control rats. AG plus a 60
      min immobilization (IMM(60)) stress on day 1 resulted in significantly greater
      facilitation as compared to the AG+IMM(10) pretreatment. It is apparent that
      facilitation of the HPA axis is dependent on the duration of stress. Stress can
      alter plasma corticosterone-binding globulin levels and AG administration can
      cause accumulation of the corticosterone biosynthetic precursor, adrenal
      cholesterol. In order to rule out these peripheral reasons for the hypersecretion
      of ACTH and corticosterone in our paradigm, we measured the plasma free fraction
      of corticosterone and adrenal mitochondrial cholesterol levels on day 2 after
      different pretreatments on day 1. AG+IMM(60) pretreatment caused a significant
      increase in the plasma free fraction of corticosterone. Hypersecretion of ACTH
      and corticosterone in this group, despite an enhanced feedback signal, suggests
      central loci for the origin of facilitation. Also, AG treatment on day 1 did not
      result in accumulation of free or esterified adrenal cholesterol levels on day 2,
      and therefore cannot account for the hypersecretion of corticosterone. In our
      final study we attempted to determine if serotonin released during the first
      stressor is partially responsible for stress-induced facilitation of the HPA
      axis. We administered 8-hydroxy-2-(di-n-propylamino)tetralin (DPAT), a 5HT(1A)
      agonist, either alone or in conjunction with stress and examined the effects of
      these pretreatments on the magnitude of facilitation. Interestingly, DPAT
      administered in lieu of stress produced facilitation similar in magnitude to that
      produced by IMM(10). DPAT administered in conjunction with IMM(10) augmented
      stress-induced facilitation. Our results suggest that stress-induced facilitation
      of the HPA axis is associated with the release of serotonin during stress.

PMID- 11528219
TI  - Melatonin receptor subtype MT2 (Mel 1b) and not mt1 (Mel 1a) is associated with
      melatonin-induced enhancement of cell-mediated and humoral immunity.
AB  - Individuals of many vertebrate species undergo seasonal changes in immune
      function in addition to marked seasonal changes in reproductive, metabolic, and
      other physiological processes. Despite growing evidence that photoperiod mediates
      seasonal changes in immunity, little is known regarding the neuroendocrine
      mechanisms underlying these changes. Enhanced immune function in short days is
      correlated with increased duration of nightly melatonin secretion, and recent
      studies indicate that melatonin can act directly on immune cells to enhance
      immune function. It remains unknown, however, which melatonin receptor subtype
      mediates immune enhancement by melatonin. The present study examined the
      contribution of specific melatonin receptor subtypes, mt1 (Mel 1a) and MT2 (Mel
      1b), in mediating melatonin-induced enhancement of cell-mediated and humoral
      immune function in mice. Melatonin enhanced both splenocyte proliferation and
      anti-keyhole limpet hemocyanin (KLH) IgG concentrations in both wild-type (WT)
      and mice lacking a functional gene for melatonin receptor mt1 (mt1 -/-),
      suggesting that the mt1 receptor does not mediate these responses. In addition,
      luzindole, an MT2 receptor antagonist, attenuated melatonin-induced enhancement
      of splenocyte proliferation in both WT and mt1 -/- mice. Taken together, these
      results suggest that receptor subtype mt1 is not necessary for mediating
      melatonin-induced enhancement of immune function and provide the first evidence
      for a specific melatonin receptor subtype, MT2, that may be involved in melatonin
      induced immune enhancement.

PMID- 11528220
TI  - Role of gonadal steroids in the corticotropin-releasing hormone and
      proopiomelanocortin gene expression response to Delta(9)-tetrahydrocannabinol in
      the hypothalamus of the rat.
AB  - Chronic exposure to Delta(9)-tetrahydrocannabinol (Delta(9)-THC) increases
      corticotropin-releasing hormone (CRH) and proopiomelanocortin (POMC) gene
      expression in the rat hypothalamus. The levels of circulating gonadal steroids
      concurrently modulate both neuropeptides in male and female rats. However, it
      remains unknown whether gonadal steroids regulate Delta(9)-THC effects on CRH and
      POMC gene expression in the hypothalamus of male and female rats. To explore this
      hypothesis, experiments were conducted on intact, 2-week-gonadectomized, 1-week
      gonadectomized, 1-week-dihydrotestosterone (DHT)- or estradiol-replaced male and
      female rats. One week after hormonal replacement, animals were treated with
      vehicle or Delta(9)-THC (5 mg/kg/day, i.p. for 7 days). Administration of
      Delta(9)-THC to intact male rats increased CRH gene expression. Castration
      abolished Delta(9)-THC effects of CRH gene expression in males but not in
      females. On the other hand, POMC mRNA levels were reduced as a result of
      castration, and DHT treatment did not prevent this decrease. Delta(9)-THC
      treatment similarly increases POMC gene expression of intact, orchidectomized and
      DHT-replaced males. In females, ovariectomy decreased CRH gene expression.
      Delta(9)-THC administration increased CRH gene expression to the same extent in
      castrated and estradiol-replaced rats. On the other hand, POMC gene expression
      was increased by ovariectomy, and Delta(9)-THC administration did only increase
      POMC transcript levels in the estradiol-replaced group. These data show that
      gonadal steroids differentially regulate the effects of Delta(9)-THC on both CRH
      and POMC gene expression in the hypothalamus of male and female rats, suggesting
      gender differences in the reaction to cannabinoids.

PMID- 11528221
TI  - Expression of functional melanocortin-4 receptor in the hypothalamic GT1-1 cell
      line.
AB  - Mutations in the melanocortin-4 receptor (MC4-R) cause obesity in both mice and
      humans, and the receptor is presumed to have an important role in the regulation
      of energy homeostasis. The MC4-R is expressed in discrete sets of neurons in the
      central nervous system, and thus it has been technically difficult to study the
      regulation of expression and the signaling mechanisms of this receptor. We report
      here a neuronal cell line that exhibits endogenous functional expression for the
      MC4-R. Initially, RT-PCR analysis showed the presence of MC4-R RNA in the
      hypothalamic GT1-1 and GT1-7 cells. In addition, GT1-7 cells expressed
      melanocortin-3 receptor while the GT1-1 subclone specifically expressed
      predominantly the MC4-R RNA. High-affinity binding sites were demonstrated in the
      GT1-1 and GT1-7 cells for NDP-alpha melanocyte-stimulating hormone (MSH; K(i) =
      1.1 x 10(-10) and 1.8 x 10(-10) M) and agouti-related protein (AGRP; K(i) = 1.548
      x 10(-9) and 1.663(-9) M). alpha-MSH-stimulated cAMP production in GT1-1 cells
      with an EC(50) of 2.2 x 10(-8) M, and cAMP production was inhibited in the
      presence of AGRP, an endogenous antagonist of the MC4-R. Stimulation of
      gonadotropin-releasing hormone (GnRH) secretion was achieved with 1 nM to 1
      microM concentrations of NDP-alpha-MSH while no GnRH secretion was observed when
      the GT1-1 cells were treated with AGRP. The data presented here show that GT1-1
      cells specifically express a functional MC4-R that couples to GnRH release.

PMID- 11528222
TI  - Structure and biological activity of gonadotropin-releasing hormone isoforms
      isolated from rat and hamster brains.
AB  - Rat and hamster brain tissues were used to investigate the possible existence of
      a follicle stimulating hormone (FSH)-releasing factor with similar
      characteristics to the lamprey gonadotropin-releasing hormone III (lGnRH-III)
      form proposed in previous reports. The present studies involved isolation and
      purification of the molecule by high-performance liquid chromatography (HPLC),
      identification by radioimmunoassay, sequence analysis by automated Edman
      degradation, mass spectrometry and examination of biological activity.
      Hypothalamic extracts from both species contained an HPLC fraction that was
      immunoreactive to GnRH and coeluted with lGnRH-III and 9-hydroxyproline mGnRH
      ([Hyp(9)]GnRH). Determination of primary structure from purified total brain
      material demonstrated that the isolated molecule was [Hyp(9)]GnRH. This is the
      first report showing the presence of the posttranslationally modified form
      already known as [Hyp(9)]GnRH by primary sequence analysis. The biological
      activity of distinct GnRH peptides was also tested in vitro for gonadotropin
      release using rat pituitary primary cell cultures. The results showed that
      [Hyp(9)]GnRH stimulated both luteinizing hormone and FSH release, as already
      reported, whereas lGnRH-III had no action on the secretion of either
      gonadotropin.

PMID- 11528223
TI  - Proto-oncogene Ets-1 and the kidney.

PMID- 11528224
TI  - The insulin-like growth factor system in kidney diseases.
AB  - The insulin-like growth factor system is intimately involved in renal
      development, growth, function and the pathophysiology of several disease states.
      Exogenous IGF-I increases GFR and RPF, perhaps mediated by nitric oxide (NO). In
      chronic renal failure, IGF-I, the binding proteins and their fragments decrease
      bioavailability. After transplantation, the levels of bioactive IGF-I increase
      likely due to better nutrition and increased clearance of the binding proteins
      and their fragments. In the nephritic syndrome, a similar mechanism may be
      active, in that the binding proteins and their fragments may inhibit IGF-I
      action.

PMID- 11528225
TI  - Long-term outcome after percutaneous transluminal coronary angioplasty in
      patients with chronic renal failure with and without diabetic nephropathy.
AB  - OBJECTIVE: Percutaneous transluminal coronary angioplasty (PTCA) in patients on
      maintenance hemodialysis leads to high rates of restenosis and postinterventional
      complications. The additional influence of diabetes mellitus on the results of
      PTCA in patients with diabetic nephropathy and reduced but sufficient renal
      function has not been investigated before. METHODS: In a retrospective case
      control study, 51 patients with reduced renal function were compared to 71
      matched controls. Patients with elevated creatinine values were divided in two
      subgroups: diabetic nephropathy (diabetes, n = 15) and stable renal insufficiency
      (renal failure, n = 36). RESULTS: The control group had normal renal function
      (creatinine: 1.0 +/- 0.01) and a mean survival time of 3.6 +/- 0.8 years.
      Patients with renal failure showed a mean survival time of 2.7 +/- 0.3 years (p <
      0.001), creatinine values of 2.0 +/- 0.2 and elevated fibrinogen values of 401 +/
      28 (p < 0.01). Patients with diabetes (creatinine: 2.2 +/- 0.2) had a
      significantly higher mortality rate with a reduced mean survival time of 1.25 +/-
      0.3 years (p < 0.001), postinterventional acute renal failure (n = 2, p < 0.01)
      and Re-PTCA (n = 2, p < 0.05). DISCUSSION: Patients with reduced but stable renal
      function showed a higher mortality than comparable patients from the control
      group. The group of patients with diabetic nephropathy has a poor prognosis after
      PTCA even though renal function was only moderately reduced.

PMID- 11528226
TI  - Elevation of blood (1-->3)-beta-D-glucan concentrations in hemodialysis patients.
AB  - Determination of the blood (1-->3)-beta-D-glucan (beta-DG) concentration is a
      sensitive marker to detect the presence of deep mycosis and fungal infections.
      Although cellulose material is known to contain beta-DG, the influence of a
      cellulose dialyzer membrane on the blood beta-DG level remains to be elucidated.
      In this study, we determined the plasma beta-DG levels in dialysis outpatients
      using either a modified regenerated cellulose (MRC) or a synthetic polysulfone
      (PS) membrane for more than 3 months. Plasma beta-DG levels were extremely high
      in patients using the MRC (2,778 +/- 549 pg/ml, n = 9) but not the PS membrane
      (18.8 +/- 3.7 pg/ml, n = 8) compared to normal ranges (<20 pg/ml). A single
      dialysis session using the MRC membrane further increased blood beta-DG values to
      5,561 +/- 722 pg/ml (p < 0.01). After changing the membranes from MRC to PS, the
      blood beta-DG levels gradually decreased and reached 29.6 +/- 6.0 pg/ml at 6
      months. In contrast, the PS membrane did not affect plasma beta-DG levels after a
      single dialysis session (16.0 +/- 3.9 pg/ml) or 4 months later (24.0 +/- 4.9
      pg/ml). These findings suggested that a cellulose membrane could influence the
      measurement of blood beta-DG concentrations in the long-term. Careful assessment
      is required to diagnose the presence of fungal infection in HD patients using a
      cellulose membrane.

PMID- 11528227
TI  - Plasma adrenomedullin levels in patients on hemodialysis.
AB  - Adrenomedullin (AM) is a hypotensive peptide that has recently been isolated from
      human pheochromocytoma. In this study, we measured plasma AM concentrations in 54
      patients on hemodialysis (HD) and examined the clinical significance. We also
      evaluated the effects of high-flux and low-flux dialysis membranes on plasma AM
      levels. The average value of plasma AM at pre-HD (4.44 +/- 0.16 fmol/ml) was
      significantly elevated compared with that in 44 healthy volunteers (1.31 +/- 1.41
      fmol/ml) (p < 0.0001). The plasma AM concentrations at pre-HD showed a negative
      correlation with age and mean blood pressure (MBP) at pre-HD. The plasma AM
      concentrations at post-HD showed a negative correlation with MBP at post-HD and a
      negative correlation with the reduction rate of AM. Multiple regression analysis
      showed that age and MBP were independent factors associated with plasma AM at pre
      HD and that MBP and reduction rate of AM were independent factors associated with
      plasma AM at post-HD. We investigated the differences between high-flux dialyzers
      (PS-UW, PS-N and FB-F) and a low-flux dialyzer (AM-BC-F), and we found that high
      flux dialyzers removed plasma AM more efficiently than a low-flux dialyzer did.
      In addition, in 3 patients on HD, plasma AM levels decreased significantly during
      isovolumic dialysis using a high-flux dialyzer, despite the fact that there were
      no significant changes in MBP and ANP. In conclusion, elevation in plasma AM
      level causes a fall in MBP in patients on HD, therefore, removal of AM by HD
      treatment using a high-flux dialyzer contributes to the stability of blood
      pressure during HD.

PMID- 11528229
TI  - Cerebral imaging changes in patients with chronic renal failure treated
      conservatively or in hemodialysis.
AB  - BACKGROUND: Nonuremic patients with apparently normal memory and behavior,
      studied by means of cerebral computed tomography and found to have cerebral
      atrophy (CA), evidenced functional intellectual deficits when they underwent
      psychometric testing. The finding of CA has been repeatedly reported in limited
      case groups of uremic patients who also demonstrated functional intellectual
      deficits on the basis of the same tests. This retrospective study considered all
      diagnostic cerebral computed tomography scans done in our department between 1981
      and 1998. Fifty-five uremic patients in conservative treatment (CT) and 111
      patients in hemodialysis treatment (HT) were selected on the basis of the
      following two criteria: primary nephropathy as the cause of uremia and an age <
      or =55 years to exclude involutive brain changes occurring with age. AIMS: The
      aims of the study were to determine the percent of uremic patients with CA, the
      characteristics of their CA (cortical or subcortical), and eventual associated
      morphological lesions. RESULTS: CA was detected in 50.9% (cortical atrophy in
      47.3% and subcortical atrophy in 3.6%) of the uremic patients in CT and in 77.5%
      of those in HT (cortical atrophy in 65.7% and subcortical atrophy in 7.7%). The
      average degree of CA was 0.872 in the patients in CT and 1.765 in the patients in
      HT. Thirty-four of the patients in the CT group and 46 in the HT group were
      hypertensive: these patients had a more severe degree of CA than the
      nonhypertensive subjects. In the CT group, the degree of CA in the hypertensive
      patients was 1.205 versus 0.428 for the nonhypertensive subjects. In the HT
      group, the degree of CA was 2.087 for the hypertensive patients versus 1.538 for
      the nonhypertensive patients. Of the overall population, 7.8% had ischemic
      lesions, 9.6% had endocranial calcifications, and 5.4% evidenced periventricular
      white matter hyperintensities. CONCLUSIONS: The high percent of CA found in young
      uremic patients increased in subjects in HT and, even more so in hypertensive
      patients. Vascular calcifications, focal ischemia and leukoaraiosis, well-known
      expressions of a chronic state of cerebrovascular insufficiency, were also found
      in HT patients; hypertension alone is a recognized accelerator of vascular
      damage. Thus, early and severe atherosclerosis and related hypoperfusion can be
      considered as the paramount causes of parenchymal cerebral damage in uremia.

PMID- 11528228
TI  - High incidence of severe twin hemodialysis catheter infections in elderly women.
      Possible roles of insufficient nutrition and social support.
AB  - BACKGROUND: Cuffed-tunneled hemodialysis (HD) catheters are recommended as a
      bridging therapy until peripheral access is available, but their long-term use is
      controversial. AIM: To evaluate the complications and lifetime of twin-tunneled
      HD catheters and to identify parameters which could predict their outcome.
      METHODS: 29 chronic HD patients (19 female and 10 male) were inserted with twin
      hemodialysis catheters (28 Tesio, 1 Schon Duoflow), followed for up to 9 months
      or until catheter loss, and evaluated for severe catheter-related complications
      necessitating catheter removal. Since the most common severe complication was
      catheter-related infection, we retrospectively examined whether parameters such
      as age, gender, duration of end-stage renal disease, delivered dose of dialysis,
      nutrition, diabetes and indices of social support correlate with this outcome.
      RESULTS: Severe catheter infection requiring catheter removal occurred in 11
      patients (10 female). Of these infected female patients, 9 were elderly (> or =67
      years) and in 6 of those, catheter infection was fatal (54% of infected cases).
      At 9 months, severe catheter infection and related patient death rates were 38
      and 21%, respectively. Severe catheter infection was significantly related to
      less social support (p < 0.005), older age, female gender, lower nPCR (all p <
      0.05), and tended to be related to shorter end-stage renal disease duration prior
      to catheter insertion (p = 0.06). CONCLUSION: This study demonstrated that twin
      HD catheters are associated with a high incidence of severe catheter-related
      infections which was most significantly related to social-support as well as
      inadequate nutrition, older age and female gender. Therefore, we suggest early
      removal of the catheter, enhancement of social support and dietary counseling for
      the elderly and lonely HD patients using this type of catheter.

PMID- 11528230
TI  - Assessment of the length of each hemodialysis session by on-line dialysate urea
      monitoring.
AB  - Hemodialysis (HD) prescription is usually based on the periodical measurement of
      the Kt/V achieved in a midweek dialysis session. The purpose of the study was to
      assess the duration of each HD session to achieve a target dose of dialysis. This
      allowed to determine whether a given dialysis session may be considered
      representative of the other HD sessions. Seventy-two HD sessions were studied in
      4 stable patients, who were randomly dialyzed during 3 consecutive periods, each
      lasting 2 weeks, using a different blood flow rate (Qb) in each period: 400, 300
      or 200 ml/min. All HD were prolonged to achieve an on-line dialysate urea monitor
      (UM) Kt/V of 1.2. The UM Kt/V was compared with the Kt/V calculated using pre-HD,
      post-HD and rebound (45 min post-HD) plasma water urea concentrations. Comparison
      of the duration of the second midweek dialysis session with the length of the
      other HD showed 95% concordance intervals (+/-2 SD) of +/-21.08 min for Qb 400,
      +/-26.88 min for Qb 300 and +/-37.02 min for Qb 200 ml/min. The 95% concordance
      intervals for whole body urea clearance were +/-32.0, +/-20.36 and +/-15.62
      ml/min for Qb 400, 300 and 200 ml/min, respectively. No differences were observed
      between UM Kt/V and blood-based double-pool Kt/V obtained by the second
      generation Daugirdas (1.18 +/- 0.08) and Garred (1.19 +/- 0.08) Kt/V formulas. In
      conclusion, a great variability was observed between different HD sessions with
      regard to the whole body urea clearance and the time required to attain a target
      Kt/V even when the HD characteristics remained constant. The length of every HD
      required to achieve a target dose of dialysis can be assessed by on-line
      dialysate urea monitoring.

PMID- 11528231
TI  - Correlation between peritoneal mesothelial cell cytology and peritoneal
      histopathology with respect to prognosis in patients on continuous ambulatory
      peritoneal dialysis.
AB  - BACKGROUND: Sclerosing encapsulating peritonitis (SEP) is a serious complication
      seen in patients on long-term continuous ambulatory peritoneal dialysis (CAPD).
      We have previously reported that mesothelial cells in effluent dialysate
      significantly increased in size as the duration of CAPD progressed. In this
      study, we investigated the relationship between mesothelial cytology,
      histopathology of the peritoneum, and clinical outcomes of 34 CAPD patients.
      METHODS: When peritoneal dialysis catheters were inserted (n = 7) or removed (n =
      27), a peritoneal biopsy was performed and results compared with mesothelial
      cytology in effluent dialysate. RESULTS: A significant positive correlation was
      noted between the duration of CAPD and the surface area of peritoneal mesothelial
      cells (r = 0.721, p < 0.0001). The surface area of mesothelial cells in
      peritoneal sclerosis (n = 9; 584 +/- 97 microm(2)) was significantly greater than
      in peritoneal fibrosis (n = 14; 389 +/- 26 microm(2), p < 0.05), pathologic acute
      peritonitis (n = 3; 223 +/- 10 microm(2), p < 0.005), and normal peritoneum (n =
      7; 247 +/- 12 microm(2), p < 0.001). The surface area in sclerosing peritonitis
      (n = 1; 1,200 microm(2)) was greater than that of all the others. Giant cells
      were found in the 1 case with sclerosing peritonitis and in 3 of 9 cases with
      peritoneal sclerosis, although they were found in only 1 of 14 patients with
      peritoneal fibrosis and in none of those with pathologic acute peritonitis or
      normal peritoneum. As the surface area of mesothelial cells increased to more
      than 400 microm(2) and giant cells appeared in the effluent, the frequency of
      peritoneal sclerosis and/or clinical SEP increased. CONCLUSION: An increase in
      the mesothelial cell surface area and the emergence of giant cells in the
      effluent indicate advanced peritoneal histopathology, and may be useful
      indicators to determine appropriate timing of discontinuation of CAPD to prevent
      the development of SEP.

PMID- 11528232
TI  - The molecular basis of Dutch infantile nephropathic cystinosis.
AB  - Infantile nephropathic cystinosis, an inborn error of metabolism with an
      autosomal recessive inheritance pattern, is characterized by lysosomal storage of
      the amino acid cystine due to an impaired transport of cystine out of the
      lysosomes. Initial clinical features consist of the renal Fanconi syndrome and
      crystals in the cornea. Oral therapy with cysteamine lowers the intracellular
      cystine content. Recently, the gene coding for the integral membrane protein
      cystinosin, which is responsible for membrane transport of cystine (CTNS), was
      cloned. Mutation analysis of the CTNS gene of Caucasian patients revealed a
      common 57-kb deletion, and several other mutations spread throughout the entire
      gene. In the present study, we developed an improved screening method for the
      detection of the common 57-kb deletion. By use of this method we detected the 57
      kb deletion in 59% of the examined Dutch alleles. The remaining alleles were
      screened for other mutations by genomic sequencing of the different exons,
      revealing three previously described mutations. Furthermore, we studied a
      possible genotype-phenotype relation of the homozygous deleted patients, which
      could not be demonstrated in our study population. Next to biochemical
      determination of cystine in leukocytes or fibroblasts, molecular genetic analysis
      enables prenatal diagnosis and facilitates identification of carriers.

PMID- 11528233
TI  - Trans-tubular potassium gradient in patients with drug-induced hyperkalemia.
AB  - BACKGROUND: Trans-tubular potassium gradient (TTKG) is considered to reflect
      mainly aldosterone bioactivity with regard to its kaliuretic response. We
      determined both TTKG and aldosterone serum concentrations in patients with severe
      drug-induced hyperkalemia (DIH). METHODS: Ten hyperkalemic patients with serum
      potassium of more than 5.5 mEq/l, and serum creatinine of less than 2.5 mg/dl
      (221 micromol/l) were studied prospectively. Two control groups of 10 patients
      each were used. Control 1 group with normal renal function, and control 2 group
      with normokalemia and renal failure of the same magnitude as that of the
      hyperkalemic patients. Serum osmolarity, electrolytes, creatinine, aldosterone
      and urine electrolytes and osmolarity were measured and TTKG calculated. RESULTS:
      DIH patients had lower TTKG values than control 1 patients (2.58 +/- 0.36 vs.
      6.68 +/- 0.55, p < 0.001), and also lower than that of the control 2 patients
      (2.58 +/- 0.36 vs. 5.51 +/- 0.87, p < 0.01). Serum aldosterone concentration in
      the DIH group was higher than that of the control 1 group [24.30 +/- 5.0 vs. 7.4
      +/- 2.1 pg/ml (674 +/- 139 vs. 205 +/- 58 pmol/l), p < 0.006] but not different
      from that of the control 2 group [24.3 +/- 5.0 vs. 15.3 +/- 3.8 pg/ml (674 +/-
      139 vs. 424 +/- 106 pmol/l), respectively, p = 0.18]. Although there was some
      overlap in TTKG between DIH and control groups, 6 of 10 DIH patients had TTKG of
      less than 2.5, while none of the control patients had such a low value.
      CONCLUSION: DIH is characterized by lower TTKG values than those observed in
      patients with normal or mild-to-moderate renal failure. Other factors in addition
      to aldosterone seem to be involved.

PMID- 11528234
TI  - Pharmacokinetics of abacavir in HIV-1-infected patients with impaired renal
      function.
AB  - BACKGROUND: Abacavir is a potent, novel 2'-deoxyguanosine analogue reverse
      transcriptase inhibitor (NRTI) which effectively suppresses HIV-1 replication. To
      date, there is no pharmacokinetic study in patients with renal impairment.
      METHODS: Five HIV-1-infected patients with various degrees of renal dysfunction
      (creatinine clearance 60, 40, 25, 20 and 1 haemodialyzed patient) were evaluated
      after being treated for at least 2 months with multi-antiretroviral therapy
      including abacavir. After an overnight fast, the subjects received their abacavir
      dosage (600 or 300 mg). Blood samples were withdrawn and plasma concentrations
      determined. A nonparametric pharmacokinetic analysis was then performed. The
      dialysability of abacavir was also evaluated. RESULTS: Time of maximum plasma
      concentration (T(max)) was constant among the subjects with a mean value of 0.7
      +/- 0.27 h (range 0.33-1). Maximum plasma concentration (C(max)) ranged from 2.76
      to 4.15 mg/l (mean 3.44 +/- 0.59). The elimination half-life ranged from 1.31 to
      2.67 h (mean 2.08 +/- 0.51). Normalized C(max)/dose ranged from 0.007 to 0.014
      mg/l and normalized AUC(0-inf)/dose ranged from 0.014 to 0.035 mg.h/l. In
      haemodialysis the dialysance was 60-80 ml/min with a fractional drug removal of
      24% during a 4-hour haemodialysis session with a high permeability membrane.
      DISCUSSION: In our patients, absorption, elimination and distribution phases were
      not altered by renal insufficiency. Furthermore, our pharmacokinetic data are
      similar to those obtained in patients with normal renal function. Therefore,
      dosage adjustment is not necessary in patients with renal insufficiency. In
      haemodialyzed patients, treatment can be administered independently to the
      dialysis session because of the negligible elimination of abacavir in the
      dialysate.

PMID- 11528235
TI  - Nephrotic origin hyperlipidemia, relative reduction of vitamin E level and
      subsequent oxidative stress may promote atherosclerosis.
AB  - BACKGROUND: The relation between nephrotic syndrome and atherosclerosis has not
      yet been fully clarified, although the high levels of low-density lipoprotein
      cholesterol usually found in this syndrome may give rise to atherosclerosis. This
      study was intended to test the disturbances of antioxidant/oxidant status in
      children with nephrotic syndrome (NS). METHODS: 8 children in the active stage
      (AS) of NS, 7 children during the remission stage (REM) of NS, and 14 control
      subjects (CTRL) were enrolled into the study. The levels of plasma total
      cholesterol (TC), HDL-cholesterol (HDL-chol), LDL-cholesterol (LDL-chol),
      triglycerides (TG), vitamin E and 7-ketocholesterol (7KCH) before and after
      plasma saponification were measured. RESULTS: A significant increase in the
      concentrations of TC, LDL-chol, vitamin E and total 7KCH in AS patients have been
      found. These patients had also a lower vitamin E/LDL-chol ratio. These changes
      have not been observed in the remission stage of nephrotic syndrome. Higher
      amounts of electronegatively charged-(oxidized) LDL particles as well as
      different oxysterols in AS patients have also been demonstrated. CONCLUSION: The
      study revealed significant disturbances in oxidant status during NS leading to
      plasma accumulation of oxidized LDL and cholesterol oxidation products that exert
      cytotoxicity and are known to induce atherosclerosis. We suggest that this may
      constitute an important link between nephrotic syndrome and atherosclerosis.

PMID- 11528236
TI  - Characterization of aldose reductase from the thick ascending limb of Henle's
      loop of rabbit kidney.
AB  - BACKGROUND: The organic osmolyte sorbitol plays an important role in the
      osmoregulation of immortalized epithelial cells of the thick ascending limb of
      Henle's loop (TALH) of rabbit. The intracellular sorbitol content seems to depend
      strongly on the extracellular osmolarity. To investigate the nature of the
      osmotic regulation we characterized the aldose reductase. METHODS: We determined
      aldose reductase activity enzymatically and the content of organic osmolytes by
      HPLC. RESULTS: The aldose reductase activity correlates with the extracellular
      tonicity. Elevating the osmolarity of the medium from 300 to 600 mosm/l by
      addition of NaCl or sucrose resulted in a significant increase of maximal
      velocity (V(max)) of the adapted cells from 8 +/- 1 micromol/g x min (300 mosm/l)
      to 322 +/- 28 micromol/g x min (600 mosm/l, NaCl) or 54 +/- 9 micromol/g x min
      (600 mosm/l, sucrose), respectively, while affinity (K(m)) remained unchanged.
      But we found no rise of aldose reductase activity when extracellular urea
      concentration was elevated. Similar alterations in V(max) were observed when the
      activity of the highly enriched enzyme was determined with glucose as substrate.
      Elevation of the extracellular osmolarity by NaCl and sucrose strongly induced
      the expression of aldose reductase protein with an apparent molecular weight of
      39 kD. The affinity of glucose is characteristically low with a K(m) above 300
      mmol/l. Aldose reductase utilizes both NADPH and with lower affinity NADH as
      coenzymes. In vitro sulfate ions (0.4 mol/l) results in a two-fold activation of
      the aldose reductase activity whereas sodium (200-400 mmol/l) decreased the
      activity significantly (22-33%). Potassium and chloride up to 400 mmol/l did not
      alter the aldose reductase activity in vitro. CONCLUSIONS: These results indicate
      that the aldose reductase of TALH cells of the outer medulla is osmotically
      regulated and has many similarities with aldose reductase in renal inner medulla.
      Therefore, intracellular sorbitol synthesis seems to be of similar importance in
      the osmoregulation of TALH cells as in the inner medulla.

PMID- 11528237
TI  - Cortical Na+,K+-ATPase activity, abundance and distribution after in vivo renal
      ischemia without reperfusion in rats.
AB  - The aim of our work was to study the changes in activity, abundance and
      distribution of sodium, potassium-adenosine triphosphatase (Na+,K+-ATPase) in
      membranes of cortical tubular cells in an in vivo model of ischemic injury
      without reperfusion. Na+,K+-ATPase, alkaline phosphatase (AP) activities and
      their distribution in membranes isolated from renal cortex using a Percoll
      gradient were studied after different ischemic periods. Na+,K+-ATPase alpha
      subunit protein abundance was analysed by Western-blot. Plasma urea and cortical
      adenosine 5' triphosphate (ATP) were also measured. In cortical homogenates 5 min
      of ischemia promoted a diminution in ATP content. Na+,K+-ATPase activity
      diminished after 40 min and AP after 100 min of ischemia. Na+,K+-ATPase activity
      in the Percoll gradient fractions after 5 min peaked at a higher density and was
      significantly decreased after 40 min. AP activity was decreased in typically
      enriched apical membranes after both times of ischemia. At each time studied
      Na+,K+-ATPase abundance was increased in cortical homogenates and membranes. Our
      results showed opposite effects of ischemia on Na+,K+-ATPase activity and
      abundance. Increased levels of Na+,K+-ATPase protein were observed. The enzyme
      would be rapidly delivered to membrane domains and become inactivated as ischemia
      persists.

PMID- 11528238
TI  - Biochemical, histological and behavioral consequences of nephrectomy in young and
      aged mice.
AB  - BACKGROUND: This study investigates the effect of nephrectomy in young and aged
      mice on some biochemical, histological and behavioural aspects. METHODS: Each age
      group, 2- and 12-months-old, comprised a sham-operated group, a unilaterally
      nephrectomized group and a subtotally nephrectomized group. Consequences of
      nephrectomy were examined 10 days postsurgery on urea and guanidino compound
      levels in body fluids and brain; the remaining kidney by light-microscopic
      examination; and learning and memory abilities using the Morris water maze task.
      RESULTS: Effect of nephrectomy on urea and guanidino compound levels in plasma,
      urine and brain was significantly more pronounced in the young age group. Some
      guanidino compounds show a tendency to decrease with aging in the sham-operated
      group and the two nephrectomized groups. Higher compensatory kidney hypertrophy
      was found in younger nephrectomized mice whereas in older mice glomerular
      mesangial expansion was a common feature. Finally, young mice with subtotal
      nephrectomy displayed a slight but significant impairment in memory and learning;
      whilst old nephrectomized mice manifested no impairment. CONCLUSIONS: Nephrectomy
      induces more changes in younger mice than in older mice as observed in higher
      variation of urea and guanidino compound levels, glomerular volume and kidney
      hypertrophy and decline in spatial learning and memory.

PMID- 11528239
TI  - Pharmacokinetics of cetirizine in chronic hemodialysis patients: multiple-dose
      study.
AB  - The serum concentration-time profiles of cetirizine were measured in 8 male end
      stage renal failure (ESRF) patients on chronic hemodialysis (HD). Cetirizine (5
      mg) was ingested three times a week during the predialysis period. Blood samples
      were drawn for basal level evaluation, before and after dialysis on 3 days per
      week, and before HD the following week. The serum levels of cetirizine were
      measured using a validated atmospheric-pressure ionization liquid chromatography
      tandem mass spectrometry method. Basal levels of cetirizine in HD patients were
      confirmed to be 0 ng/ml. The predialysis levels of cetirizine on days 1, 3, 5,
      and 8 were (mean +/- SD) 2.74 +/- 7.76, 34.16 +/- 21.55, 35.58 +/- 13.43, and
      22.47 +/- 12.92 ng/ml, respectively. The postdialysis levels of cetirizine 4-5 h
      after ingestion were as follows (ng/ml): day 1, 103.11 +/- 37.27; day 3, 131.34
      +/- 51.18, and day 5, 136.48 +/- 48.72. Between dialysis sessions, no
      supplemental dosage was required to keep the therapeutic range of 14 ng/ml. In
      addition, the predialysis levels on day 8 were not statistically different from
      the basal levels. Evidence from the multiple-dose study supports the clinical use
      of cetirizine for ESRF patients on HD. Thus, it is concluded that a prescription
      of 5 mg cetirizine three times a week during the predialysis period will be the
      effective and safety renal dosage for ESRD patients on HD.

PMID- 11528240
TI  - Persistent post-transplant autonomous hyperparathyroidism despite 23 years of
      excellent renal allograft function.
AB  - Hyperparathyroidism is a common problem for patients on renal replacement therapy
      programs. Many long-term dialysis patients require parathyroidectomy while on
      dialysis. Some patients, however, despite severe renal osteodystrophy, are
      transplanted, and in these a large proportion show a slow resolution of bony
      problems, in the context of the removal of the uremic stimulus to abnormal bone
      metabolism. A proportion of these patients become hypercalcaemic after renal
      transplantation, sometimes with symptoms. There is not a consensus on how these
      patients should be managed, with opinions varying from early parathyroidectomy to
      later parathyroidectomy and to conservative treatment. We present the case of a
      lady who underwent 23 years of conservative management of her post-transplant
      hyperparathyroidism. She was hypercalcaemic for almost all of that period,
      despite excellent renal transplant function. Finally, after 23 years she
      underwent surgical parathyroidectomy with autografting with prompt sustained
      resolution of her symptomatic hypercalcaemia.

PMID- 11528241
TI  - Metronidazole-induced encephalopathy in a uremic patient: a case report.
AB  - A variety of neurologic disorders may develop in patients with chronic renal
      failure. Drug toxicity must be thought of in the differential diagnosis of these
      disorders. We report a case with renal failure developing serious neurotoxicity
      after metronidazole use.

PMID- 11528242
TI  - Effect of weekly or successive iron supplementation on erythropoietin doses in
      patients receiving hemodialysis.
AB  - AIMS: To conduct a 3-month prospective study to determine the optimal way for
      intravenous iron supplementation in hemodialysis (HD) patients with resistance to
      recombinant human erythropoietin (rHuEPO) therapy due to deficient iron storage.
      METHODS: Thirty-five HD patients with iron deficiency were divided into three
      groups: (1) patients receiving an intravenous infusion of 40 mg of iron during
      the first ten HD sessions (n = 12); (2) patients receiving 40 mg of iron injected
      once a week for 10 weeks (n = 12), and (3) patients without any iron
      supplementation (n = 11). The rHuEPO dosage was adjusted to maintain hemoglobin
      levels >10.0 g/dl, and the degree of anemia was assessed 3 months later. RESULTS:
      In group 1, the hemoglobin levels were significantly increased after 4 weeks and
      remained increased until the end of the study (p < 0.01). In group 2, the
      hemoglobin levels were gradually increased until the end of the study (p < 0.01).
      There was no difference in the final hemoglobin values between both groups. The
      rHuEPO dosage was significantly decreased from 131 +/- 18 to 90 +/- 17 U/kg/week
      in group 1 (p < 0.01), but could not be changed in group 2 during the observation
      period despite a similar elevation of the serum ferritin level. In group 3, the
      rHuEPO doses were rather increased at the end of the study (p < 0.05).
      CONCLUSION: Aggressive iron supplementation for the short term may be effective
      to restore rHuEPO hyporesponsiveness in HD patients with functional iron
      deficiency.

PMID- 11528243
TI  - Microalbuminuria is not linked to lipoprotein oxidation in nondiabetic obese
      patients.

PMID- 11528244
TI  - Evaluation of 3- and 4-hour daytime segments of ambulatory blood pressure
      monitoring in patients on hemodialysis: can they substitute for a whole 12- or 24
      hour study?

PMID- 11528245
TI  - Rhabdomyolysis associated with concurrent use of simvastatin and diltiazem.

PMID- 11528246
TI  - Acute effect of human recombinant erythropoietin administration on soluble
      transferrin receptor.

PMID- 11528247
TI  - A literature analysis of prognostic factors for response and quality of response
      of patients with renal cell carcinoma to interleukin-2-based therapy.
AB  - OBJECTIVE: To characterize prognostic factors for response of advanced renal cell
      carcinoma to interleukin-2-based regimens. PATIENTS AND METHODS: Data compiled
      from 80 published series were examined for associations between patient
      characteristics and outcomes. RESULTS: Response rates were highest in trials
      utilizing interleukin-2 combinations. Longer median survivals were associated
      with high percentages of patients with nephrectomy, good performance status, with
      publication year, response rates, and inversely with median ages. Associations of
      performance status and prior nephrectomy with response rates were detected in
      trials with individual patient details. The response rate was higher for patients
      older than the median age of patients entering each trial, and also higher for
      males. Among responders, attainment of complete response was associated with
      fewer sites of involvement. Pooled response duration of patients reported to have
      complete responses exhibited durability, but no correlation with prognostic
      factors. Selection factors may have influenced apparent differences between types
      of regimens. We confirm the potential for durable remissions from interleukin-2
      based regimens.

PMID- 11528248
TI  - Tumor growth patterns and biological characteristics of early gastric carcinoma.
AB  - Gastric cancer is a major malignant disease. The development of new diagnostic
      techniques and mass screening have led to increased detection rates of patients
      with early-stage gastric cancer in Japan. However, after curative resection of
      early gastric cancer, there are various types of recurrences, and residual occult
      disease and distant micrometastasis precede death. The growth and metastatic
      potential of cancer cells are closely related to the postoperative outcome, and
      patients at risk for cancer-related death after surgery have to be closely
      monitored to prevent tumor recurrence. The biological behavior of cancer cells
      should be determined in patients with early gastric cancer and with a less
      favorable prognosis to detect potential early recurrences in the liver. Two types
      of growth patterns have been found in early gastric cancer: the superficially
      spreading (Super) type and the penetrating (Pen) type, and the
      clinicopathological and biological characteristics of each type have been
      extensively determined. A subtype of the Pen-type gastric cancer, which is
      progressing expansively with complete destruction of the muscularis mucosae (Pen
      A type) has a less favorable prognosis due to early recurrences in the liver.
      These clinical cancer types are closely related to chromosomal instability in DNA
      aneuploidy and p53 overexpression, and vascular endothelial growth factor
      activation induced tumor angiogenesis, vascular invasion and hematogenous
      metastasis. Thus, patients with Pen-A-type cancer showing expansive tumor growth
      had a poorer postoperative outcome and a hematogenous-related recurrence of the
      cancer. Antiangiogenic approaches in a postoperative setting may prove to be
      effective in preventing tumor recurrence and improving the prognosis for these
      patients.

PMID- 11528249
TI  - A phase I study of raltitrexed (Tomudex) combined with carmofur in metastatic
      colorectal cancer.
AB  - OBJECTIVES: The aim of the study was to define the maximum tolerated dose (MTD)
      of the combination of raltitrexed plus carmofur, and to evaluate the tolerability
      and efficacy of this combination in metastatic colorectal cancer. METHODS: Twenty
      eight patients (23 receiving first-line therapy, 5 receiving second-line therapy)
      entered the study; 16 were chemonaive. Raltitrexed (Tomudex) 1.5-3.0 mg/m(2) was
      given as a 15- to 30-min intravenous infusion on day 1 of a 21-day cycle followed
      by carmofur 300-400 mg/m(2) orally 3 times daily on days 2-14. Therapy was given
      until disease progression or dose-limiting toxicity (DLT) occurred. RESULTS: A
      total of 170 cycles of therapy were administered. The MTD was reached at the
      raltitrexed dose of 3.0 mg/m(2) and the carmofur dose of 400 mg/m(2). DLTs
      included grade 3-4 diarrhea, fatigue, anorexia, mucositis, anemia,
      thrombocytopenia, neutropenia, neurological symptoms and febrile neutropenia.
      Eleven of the 22 evaluable first-line patients achieved a partial response
      (response rate 50%, 95% confidence interval 29-71%), 8 had stable disease and 3
      had disease progression. One of the 5 patients who received second-line therapy
      responded. CONCLUSIONS: The recommended dose of this combination therapy for
      further evaluation is raltitrexed 3.0 mg/m(2) plus carmofur 300 mg/m(2). This
      combination has unique but manageable toxicity and promising efficacy in
      metastatic colorectal cancer.

PMID- 11528250
TI  - Assessment of quality of care in an oncology institute using information on
      patients' satisfaction.
AB  - OBJECTIVE: To evaluate the feasibility of conducting a patient satisfaction
      survey in the oncology hospital setting, using a multidimensional patient
      satisfaction questionnaire to be completed at home. METHODS: Socio-demographic
      and clinical data were collected for 133 consecutive patients. Patients were
      asked to complete the European Organisation for Research and Treatment of Cancer
      QLQ-C30 (version 2.0) just before hospital discharge and the Comprehensive
      Assessment of Satisfaction with Care at home 2 weeks after discharge. RESULTS:
      Respondents (73% of patients approached) were younger, hospitalized for a shorter
      time and presented less appetite loss, nausea and vomiting and better physical
      and role functioning than non-responders. The aspects of care for which patients
      wanted the most improvement were associated with the provision of medical
      information. In multivariate analyses, longer hospital stay was associated with
      higher satisfaction with all aspects of medical and nursing care, most probably
      because patients discharged early were not assured of continuity of care and
      lacked information regarding self-care at home. Higher global quality of life was
      associated with higher satisfaction with all aspects of care, suggesting the
      potential contribution of patient satisfaction to the patients' well-being.
      CONCLUSIONS: Conducting a patient satisfaction survey in an oncology hospital
      setting proved feasible; however, further surveys should attempt to obtain the
      opinion of patients with more severe physical conditions. The assessment of the
      patients' satisfaction provided indications for improvement of care in a
      particular hospital. Although the results of this study are specific to one
      hospital, the methods could be reproduced in other hospital settings, but may
      possibly lead to other conclusions.

PMID- 11528251
TI  - Hypersensitivity reactions to carboplatin administration are common but not
      always severe: a 10-year experience.
AB  - We have retrospectively evaluated and characterized the hypersensitivity
      reactions associated with carboplatin administration in ovarian cancer patients
      treated mainly on an outpatient basis at the Laikon Hospital from 1988 to 1998. A
      total of 240 patients, who had never been exposed to platinum compounds
      previously, received carboplatin plus cyclophosphamide (n = 58) or paclitaxel (n
      = 136) intravenously, and intraperitoneal carboplatin plus intravenous
      cyclophosphamide (n = 46). The median number of carboplatin courses was 6 (range
      3-12) and 5 (range 4-6) for the intravenous and intraperitoneal treatment
      regimens, respectively. Thirty-two of 194 patients (16%) who were on intravenous
      carboplatin treatment developed symptoms compatible with a hypersensitivity
      reaction to carboplatin, that was always verified by manifestation of at least
      similar symptoms on rechallenging. In contrast, in the group of 46 patients on
      intraperitoneal carboplatin treatment, no hypersensitivity reaction was ever
      noticed. Hypersensitivity reactions always occurred after administration of the
      first 4 intravenous courses of carboplatin; 4, 19, 4, and 5 reactions occurred at
      the 5th, 6th, 7th, and 8th courses, respectively. These reactions could be
      distinguished in: (a) mild hypersensitivity reactions in 20 of 194 patients,
      which manifested as itching (20 patients) and small area erythema plus erythema
      of the palms and soles (12 patients), occurring either during intravenous
      injection when most of the drug scheduled had been administered, or within 3
      days, and (b) in severe reactions in 12 of 194 patients, which manifested acutely
      as itching, diffuse erythroderma, rigor, facial swelling, throat and chest
      tightness, tachycardia (12 patients) and bronchospasm (2 patients), and
      hypertension or hypotension in 8 and 4 patients, respectively. With appropriate
      symptomatic management, discontinuation of carboplatin treatment was not required
      in patients with mild hypersensitivity reactions, but none of the 12 patients
      with severe reactions was able to receive a full subsequent dose of carboplatin
      on rechallenging. However, in 4 of these 12 patients carboplatin was replaced by
      cisplatin, which was given for 4-6 courses without side effects. These findings
      indicate that although hypersensitivity reactions are common in general,
      occurring in almost 1 of every 6 patients treated intravenously with carboplatin,
      their clinical picture is variable, leading to discontinuation of treatment in
      only 6% of patients. This is not the case when the intraperitoneal route of
      carboplatin administration is used when indicated.

PMID- 11528252
TI  - Effect of the dose and duration of interferon-alpha therapy on the incidence of
      hepatocellular carcinoma in noncirrhotic patients with a nonsustained response to
      interferon for chronic hepatitis C.
AB  - OBJECTIVE: We evaluated the effect of dose and duration of treatment with
      interferon (IFN)-alpha on the incidence of hepatocellular carcinoma (HCC) after
      IFN treatment in patients with chronic hepatitis C. METHODS: A total of 291
      noncirrhotic patients with chronic hepatitis C without hepatitis B virus
      coinfection in whom hepatitis C virus (HCV) was not eradicated by IFN-alpha
      therapy were retrospectively analyzed. The incidence of HCC after IFN therapy was
      compared according to the total dose or duration of treatment. RESULTS: Patients
      were followed up for 6-117 months after the end of IFN treatment. The duration of
      IFN treatment (< or =24 vs. >24 weeks) had no effect on the incidence of HCC.
      However, the incidence of HCC was significantly lower in patients who received
      >500 million units of IFN as a total dose than in patients who received < or =500
      million units of IFN (p = 0.0480), and the total dose of IFN (>500 million units)
      was an independent factor affecting the incidence of HCC (p = 0.0405). In
      addition, when focusing on patients whose histology was F2 or F3 before IFN
      treatment, the suppressive effect of the total dose of IFN (>500 million units)
      was emphasized (p = 0.0049 in generalized Wilcoxon test and p = 0.0178 in
      multivariate analysis). CONCLUSIONS: Patients with chronic hepatitis C should
      receive more than 500 million units of IFN when IFN is used to decrease the
      incidence of subsequent HCC.

PMID- 11528253
TI  - Chemotherapy-related hemolytic-uremic syndrome following treatment of a carcinoma
      of the nasopharynx.
AB  - OBJECTIVE: A cisplatin-containing regimen followed by radiation therapy is the
      recommended treatment for patients with advanced nasopharyngeal carcinoma. We
      report a case of a 58-year-old woman with hemolytic-uremic syndrome (HUS) who
      received induction chemotherapy for undifferentiated squamous cell carcinoma of
      the nasopharynx. PATIENTS AND METHODS: During the 2nd course of chemotherapy
      (consisting of bleomycin, cisplatin and epirubicin), the patient developed
      hemolytic anemia, thrombocytopenia, and acute renal failure. After HUS had been
      diagnosed, the patient was transferred to the intensive care unit. RESULTS: Twice
      daily therapeutic plasma exchange (TPE) with fresh-frozen plasma, hemodialysis
      and high-dose cortisone was performed. Two weeks after the start of plasma
      exchange, thrombocytes and renal function began to normalize. Low-dose cortisone
      was continued until the patient recovered from hemolytic anemia. Six weeks after
      the administration of the second course of chemotherapy, the patient had fully
      recovered from HUS, and radiation therapy was carried out as planned. The patient
      responded well to treatment, but died 9 months after the diagnosis due to liver
      metastases. CONCLUSION: We demonstrated that early TPE with fresh-frozen plasma
      and high-dose cortisone is a potentially successful treatment modality for the
      usually fatal, fulminant form of chemotherapy-induced HUS.

PMID- 11528254
TI  - Immunoreactivity of monoclonal antibody BW835 represents a marker of progression
      and prognosis in early gastric cancer.
AB  - The Thomsen-Friedenreich (TF) antigen is a well-known human pan-carcinoma
      antigen. It represents a carbohydrate core disaccharide (Gal beta 1-3GalNAc)
      which is predominantly bound to mucin peptide cores. Its immunoreactivity depends
      on changes in glycosylation which lead to a reduction in the carbohydrate chain
      length and the exposure of core carbohydrates. In the present study, we
      investigated 208 gastric adenocarcinomas with respect to their
      immunohistochemical reactivity applying two monoclonal antibodies (MAbs). MAb
      specifically detecting TF antigen (A78-G/A7) and MAb BW835 were included. The
      latter reacts with a certain glycoform of the MUC1 peptide core, characterized by
      core-type glycans like TF. A78-G/A7 epitopes were detected in 68.8% and BW835
      epitopes in 57.7% of the carcinomas. BW835 immunoreactivity correlated with the
      presence of lymph node metastases. Both A78-G/A7 and BW835 staining were
      significantly stronger in tubular/papillary cancer (WHO classification) and
      intestinal-type cancer according to Lauren. In univariate survival analyses of
      all patients studied, BW835 immunoreactivity was a marker of an unfavorable
      prognosis (p < 0.05). The presence of A78-G/A7 and BW835 epitopes exerted a
      negative effect on the subgroup of pTNM stage I carcinomas. These results
      indicate that TF and MUC1-TF immunoreactivity defines a 'high-risk' subgroup of
      stage I patients in gastric cancer.

PMID- 11528255
TI  - Genetic alterations in the human Tcf-4 gene in Japanese patients with sporadic
      gastrointestinal cancers with microsatellite instability.
AB  - Disruption of the APC/beta-catenin/Tcf pathway has been proposed as an important
      step in the development of cancer. The Tcf-4 transcription factor gene was
      reported to be one of the targets of microsatellite instability (MSI) in
      colorectal cancers in with MSI. We carried out a sequencing analysis of the Tcf-4
      gene in 41 Japanese patients with gastrointestinal tumors with MSI as well as in
      cancer cell lines. Three of 21 (14.3%) colorectal tumors with MSI contained a
      mutant Tcf-4 gene encoding 1-bp deletion in an (A)9 repeat, leading to carboxyl
      terminal truncation of Tcf-4 protein. No Tcf-4 mutations were detected in 20
      gastric tumors with MSI, or in gastric cancer cell lines. Additionally, we found
      a novel transcript of the Tcf-4 gene which contained a segment of 73 bp in front
      of the (A)9 repeat of the Tcf-4 coding sequence. Sequencing analysis revealed
      that the inserted fragment was 60% homologous to that of exon IXA of the Tcf-1
      gene. It is of interest that this insertion resulted in truncation of Tcf-4,
      similar to the 1-bp deletion in the (A)9 repeat. Therefore, in part of the
      Japanese colorectal tumors with MSI, frameshift mutations in Tcf-4 may be of
      functional significance. Functional alterations in the Tcf-4 signaling network in
      gastrointestinal tumorigenesis require further investigations.

PMID- 11528256
TI  - Expression of metallothionein in colorectal cancers and synchronous liver
      metastases.
AB  - The aim of this study is to clarify whether the expression of metallothionein
      (MT) is related with the malignant potential in primary colorectal cancer and/or
      synchronous liver metastasis. Immunohistochemical staining for MT was performed
      on the specimens of adenocarcinoma of the colon and rectum and its liver
      metastases in 34 patients treated with curative surgery, respectively. Expression
      of MT was compared with clinicopathological variables and patient survival. In
      patients with primary colorectal cancer, positive expression was found in 7 of 34
      (20.6%) patients, but MT was not detected in any of the cases of liver metastases
      (0%; p = 0.0111). In the primary tumor, positive MT expression was significantly
      associated with a higher degree of lymph node involvement (mean +/- SD: 48.4 +/-
      33.8 vs. 18.6 +/- 24.4% in MT-positive and MT-negative tumors, respectively; p =
      0.0122). The survival rate in the patients with MT-negative tumors was
      significantly better than that in those with MT-positive tumors as primary sites
      (p = 0.0198). MT expression in colorectal cancer may be a potential marker
      affecting lymph node metastases and may be a predictor of a poor prognosis,
      particularly in patients with synchronous liver metastases.

PMID- 11528257
TI  - Features of microsatellite instability in colorectal cancer: comparison between
      colon and rectum.
AB  - In one third of colorectal cancer patients, tumours occur in the rectum. Unique
      aetiologies may underlie the increased carcinogenesis in this region of the
      colorectum. Microsatellite instability (MSI) was analysed in specimens obtained
      from 121 colorectal carcinoma patients, using five dinucleotide markers and a new
      fluorescent system. The incidence of microsatellite alterations in the proximal
      colon, the distal colon and the rectum was 44.4% (16/36), 37.2% (16/43) and 23.8%
      (10/42), respectively. Patterns of microsatellite alterations could be classified
      into two subtypes, one showing relatively small changes within 6 bases (type A)
      and the other exhibiting drastic changes over 8 bases (type B). All the changes
      observed in tumours in the rectum were type A, and no type B mutation was noted.
      There was a close correlation between type B mutations and high-frequency MSI (>
      or =2 markers), MSI-H, and between type A mutations and low-frequency MSI (1
      marker), MSI-L. The type B/MSI-H phenotype significantly correlated with the
      proximal localisation of tumours. In the rectum, there was no tumour with the
      type B/MSI-H phenotype. These findings suggest that cancers occurring in the
      colon and the rectum have a differential molecular background for carcinogenesis.

PMID- 11528258
TI  - Experimental staphylococcal endophthalmitis.
AB  - Endophthalmitis is one of the most feared complications of ocular trauma or
      surgery. It is a complex pathogen- and host-mediated process that often results
      in significant vision loss. This review summarizes data from experimental models
      of staphylococcal endophthalmitis that address the host's immune response to
      intraocular staphylococci and those that investigate disease pathogenesis.

PMID- 11528259
TI  - Ocular infections due to contaminated solutions.

PMID- 11528260
TI  - Safety of ozonated solution as an antiseptic of the ocular surface prior to
      ophthalmic surgery.
AB  - PURPOSE: To evaluate the safety of an ozonated solution as an antiseptic of the
      ocular surface prior to ophthalmic surgery. METHODS: In experiment 1, a primary
      culture of rabbit corneal epithelium was established. Then, 0, 4 and 10 ppm
      ozonated solution and 1.25% povidone-iodine, respectively, were applied to
      confluent cells on collagen-coated filter inserts (Millicell-CM) for 10 min
      followed by replacement with fresh medium. The transepithelial electrical
      resistance (TER), which is a good indicator of cell barrier function, was
      sequentially measured for 30 min. In experiment 2, adult pigmented rabbit eyes
      were washed with 20 ml of 4 ppm ozonated solution, 1.25% povidone-iodine solution
      or saline. Slitlamp examinations were performed before and after washing.
      RESULTS: In experiment 1, 4 ppm ozonated solution did not change the TER as
      compared with the control. 10 ppm ozonated solution and 1.25% povidone-iodine
      similarly reduced the TER values significantly as compared with those of the
      control and 4 ppm ozonated solution. In experiment 2, 4 ppm ozonated solution and
      saline showed mild superficial punctate keratitis (SPK) in 8.3% of eyes. However,
      1.25% povidone-iodine resulted in mild SPK in 17% of eyes and moderate SPK in 25%
      of eyes. The prevalence of SPK between two groups was significantly different (p
      = 0.03). CONCLUSION: Ozonated solution may be safe and a useful antiseptic of the
      ocular surface prior to ophthalmic surgery.

PMID- 11528261
TI  - Use of topical clotrimazole in human keratomycosis.
AB  - Twelve out of 15 patients (9 males and 6 females) with laboratory-proven fungal
      keratitis were treated with topical clotrimazole, a synthetic imidazole
      derivative. Their ages ranged from 8 to 70 years. The posttreatment visual
      acuities were significantly better than the pretreatment visual acuities. No
      significant biomicroscopic signs of ocular surface toxicity were noted. The
      ocular condition in 3 patients (all infected with Fusarium solani) deteriorated
      to blindness despite the antifungal therapy. CONCLUSION: The clotrimazole usually
      marketed as dermatological preparation can be used in a diluted form to treat
      human keratomycosis safely and successfully. A combination with a polyene
      derivative should be considered in the treatment of fungal corneal infection due
      to Fusarium spp.

PMID- 11528262
TI  - The one-month effects of topical betaxolol, dorzolamide and apraclonidine on
      ocular blood flow velocities in patients with newly diagnosed primary open-angle
      glaucoma.
AB  - PURPOSE: This double-masked, prospective and randomized clinical trial was
      planned to investigate with color Doppler imaging the 1-month vascular effects of
      betaxolol, dorzolamide and apraclonidine treatment on patients with newly
      diagnosed primary open-angle glaucoma (POAG). METHODS: 22 consecutive patients
      with newly diagnosed POAG between the ages of 46 and 72 years were enrolled in
      this study. All patients were newly diagnosed cases and had not received any
      antiglaucoma medication before. Patients who had a systemic vascular disease
      (including systemic hypertension) or were taking beta-blockers, nitrates or
      calcium channel blockers were excluded from the study. The patients were randomly
      divided into three groups. Groups A and B contained 7 patients, group C contained
      8 patients. Group A patients were treated with topical betaxolol, group B
      patients received topical dorzolamide eye drops, and group C patients were
      treated with topical apraclonidine eye drops. Peak systolic velocities (PSV), end
      diastolic velocities (EDV) and resistive indices (RI) in the right ophthalmic
      arteries (OA), central retinal arteries (CRA) and posterior ciliary arteries
      (PCA) were measured at baseline by using color Doppler imaging on a masked basis.
      On days 15 and 30 of treatment, the same measurements were repeated. The inter-
      and intragroup results were compared statistically. RESULTS: Compared to
      pretreatment measurements, topical betaxolol therapy significantly decreased PSV
      only in the PCA and only on day 30 of treatment (p = 0.011). On days 15 and 30,
      dorzolamide decreased RI measurements in the PCA compared to pretreatment
      measurement (p = 0.013 and p = 0.011, respectively). Apraclonidine also decreased
      PSV in the OA on days 15 and 30 of treatment when compared to pretreatment values
      (p = 0.013 and p = 0.012, respectively). When 15-day measurements were compared
      between the groups, PSV in the OA were significantly higher in dorzolamide
      treated patients compared to other groups (p = 0.01 and p = 0.011). On day 30 of
      treatment, PSV in the OA was also higher in the dorzolamide-treated group than
      the other groups (p = 0.012 and p = 0.01). Additionally, apraclonidine-treated
      patients had a significantly lower EDV in the OA than the other groups (p = 0.013
      and p = 0.01). The RI in the OA was also significantly lower in the apraclonidine
      treated group compared to the other groups (p = 0.01 and p = 0.011). CONCLUSION:
      Our study suggests that dorzolamide has the most advantageous 1-month effects on
      blood flow velocity in the retrobulbar arterial circulation of POAG patients.
      Betaxolol seems superior to apraclonidine in this regard. Our data may help the
      clinician when treating patients with POAG medically. Further studies using a
      larger population size may clarify our results.

PMID- 11528263
TI  - A morphometric study of age changes in the rat optic nerve.
AB  - Age-related changes of the optic nerve fibres were studied in 3-month-old
      (young), 12-month-old (adult) and 24-month-old (aged) male Sprague-Dawley rats.
      The optic nerve was harvested with particular care from the intracranial portion.
      Cross sections from the optic nerve of animals of different age groups were
      stained with toluidine blue and examined under a light microscope at low and high
      magnification. Other sections were stained for the demonstration of glial cells
      using the method described by Holzer. A third group of sections were stained by
      the immunohistochemical method to detect glial fibrillary acidic protein, which
      is a marker for localising and characterising astrocytes. All these morphological
      results were subjected to the quantitative analysis of images and to statistical
      analysis of the values to identify significant morphometric data. Biochemical
      dosages of proteins were also performed on homogenised fragments of the optic
      nerve. Our results demonstrate that the following age-related changes can be
      observed: (1) an increase in meningeal membranes, (2) an increased number of
      astrocytes, (3) an increase in areal density of glial fibrillary acidic protein
      immunoreactivities, (4) an increased thickness of the entire optic nerve and an
      increased area of the nerve, (5) a decreased number of nerve fibres and (6) a
      decrease in the nerve fibre/meningeal membrane ratio from 3:1 to 1:1. Moreover,
      the amount of protein does not change with age. The rat optic nerve, therefore,
      appears sensitive to aging processes.

PMID- 11528264
TI  - Spontaneous resolution of congenital bilateral Brown's syndrome.
AB  - We report a case of bilateral Brown's syndrome in a 4-year-old girl. Forced
      duction testing confirmed the clinical diagnosis. After 7 months we observed a
      spontaneous resolution in the right eye. The problem in her left eye did not show
      any significant change over 36 months of follow-up. Various spontaneous
      resolutions in bilateral cases are reviewed.

PMID- 11528265
TI  - Intraocular pressure -- all that is raised is not glaucoma.
AB  - Increased intraocular pressure invariably sets our mind in the direction of
      either establishing or ruling out the diagnosis of glaucoma and in the process,
      sometimes, certain hidden factors may escape our attention, leading to some delay
      in delivering the specific treatment to the patient. We present a case whose
      underlying pathology remained obscured for more than 10 years before we examined
      this patient and discovered the hidden secret.

PMID- 11528266
TI  - Intraocular hemangiopericytoma. A case report.
AB  - A 55-year-old man presented with a smoothly elevated solid choroidal mass with
      choroidal detachment in the temporal region of the left eye. Both fluorescein and
      indocyanine green angiography suggested a vascularized lesion such as an angioma.
      However, radiographic examination revealed a solid, circumscribed, dome-shaped
      mass. During a 3-month observation, the mass gradually enlarged and invaded the
      iris. The possibility of malignant melanoma could not be ruled out. Due to rapid
      and continued growth of the tumor, the eye was enucleated. Histopathologic
      examination revealed proliferation of spindle-shaped cells surrounding reticulin
      positive vessels, which is characteristic of hemangiopericytoma. To our
      knowledge, this is only the fourth reported case of intraocular
      hemangiopericytoma and the first diagnosed in a male patient.

PMID- 11528267
TI  - [Ophthalmomyiasis externa acquired in Germany: case report and review of the
      literature].
AB  - Infestation with larvae (maggots) is known as myiasis. Ophthalmomyiasis externa
      refers specifically to infestation that involves the lids and conjunctiva in man.
      Ophthalmomyiasis which originates from Germany is unusual, because the vector of
      the Oestrus ovis larvae is most prevalent in the warm climate of Mediterranean
      countries. The sheep nasal botfly (Oestrus ovis sp.) is responsible for most
      cases of external ophthalmomyiasis. This case report gives a detailed description
      of the larvae, their life cycle and an overview of infestations in Germany as
      well as the therapy of ophthalmomyiasis. CASE REPORT: At the end of August 1999,
      a 28-year-old man attended the outpatient department of Giessen University Eye
      Clinic with a foreign body sensation in his left eye. He reported that something
      hit his left eye while he was climbing on his motorbike in the early evening
      hours. Shortly afterwards he had a foreign body sensation in his left eye. On
      history taking he reported no other ophthalmologic problems in the past. Slitlamp
      biomicroscopy revealed white, vivid, approximately 1.5-mm-long, light-sensitive
      maggots on the conjunctiva and under the upper lid. These were removed
      mechanically and the conjunctiva rinsed with saline. Local therapy was not
      applied. CONCLUSION: Infestation with larvae of O. ovis has to be considered not
      only in tourists from Mediterranean countries, but also in Germany in the late
      summer.

PMID- 11528269
TI  - Heterogeneity of phospholipase C in the cochlea of the guinea pig.
AB  - In the present study, we investigated the presence of phosphatidylinositol
      specific phospholipase C (PLC) isoforms in the cochlea of the guinea pig using
      Western blot analysis and immunocytochemistry. By Western blotting, PLCbeta1 and
      delta1 were expressed in the cochlear sensory epithelia (CSE) and PLCbeta1,
      gamma1 and delta1 were expressed in the cochlear lateral wall. By
      immunocytochemistry of the CSE, PLCbeta1-like immunoreactivity was mainly
      expressed in the outer hair cells (OHCs), but not in the inner hair cells (IHCs).
      PLCgamma1 and delta1 were expressed neither in the OHCs nor in the IHCs. In the
      cochlear lateral wall, PLCbeta1, delta1 and gamma1 were expressed in the stria
      vascularis and the spiral ligament. In addition, PLCbeta1, delta1 and gamma1 were
      also present in type I spiral ganglion cells. Based on these results, we
      discussed the function of these PLC isoforms in the cochlea.

PMID- 11528268
TI  - Allopurinol attenuates endolymphatic hydrops in the guinea pig cochlea.
AB  - Based on the hypothesis that Ca(2+) overload in the scala media may produce
      endolymphatic hydrops and generate free oxygen radicals (FOR), allopurinol, a
      xanthine oxidase inhibitor and free radical scavenger, was administered to guinea
      pigs after the surgical obliteration of the endolymphatic duct. Allopurinol was
      given intraperitoneally (50 mg/kg/day) for 15 days starting 1 day prior to the
      surgical blockage procedure. Measurements from histological serial sections of
      these temporal bones showed that the total volume of the scala media was
      significantly reduced (p = 0.007) compared with control hydropic ears. There was
      an indication of reduced incidence of atrophy in sensorineural structures and
      stria vascularis. These findings suggest that allopurinol may attenuate the
      development of endolymphatic hydrops and cell damage by preventing the formation
      of FOR or scavenging FOR. This study may lead to a new aspect of treatment for
      Meniere's disease.

PMID- 11528270
TI  - Aldosterone assessment in patients with Meniere's disease.
AB  - Since 1938 endolymphatic hydrops has generally been accepted as the basic
      histopathological substrate of Meniere's disease. In animal studies it has been
      found that exogenous administration of aldosterone resulted in endolymphatic
      hydrops. Manifestations of Meniere's disease are frequently observed in times of
      emotional stress. Mediated through the hypothalamus, stress leads to an increased
      secretion of adrenocorticotropic hormone from the anterior pituitary gland,
      followed by an increased adrenocortical production of glucocorticoids (cortisol
      and corticosterone) and mineralocorticoids (aldosterone). We addressed the
      question whether plasma aldosterone levels, like in guinea pigs, would be
      increased in patients with Meniere's disease. As part of a diagnostic protocol a
      clinical prospective cohort study was therefore performed on 89 patients with
      Meniere's disease to assess plasma aldosterone levels. Plasma aldosterone was not
      elevated in Meniere patients compared to plasma aldosterone in a control group of
      27 normal subjects. No statistically significant differences were found in plasma
      aldosterone between uni- and bilateral Meniere's disease. Plasma aldosterone
      levels did not correlate with age, average hearing loss, duration or perceived
      severity of subjective complaints (vertigo, hearing loss, tinnitus and aural
      pressure). In this study plasma aldosterone was not elevated in patients with
      Meniere's disease compared to normal subjects. Plasma aldosterone can thus not be
      used as a diagnostic tool for Meniere's disease. IN CONCLUSION: No anomalous
      plasma aldosterone levels were found in Meniere patients during an attack-free
      period. The question whether plasma aldosterone and cortisol levels show
      variations before, during and after an attack remains to be answered. If so, this
      might contribute to a better understanding of the pathophysiological mechanism of
      Meniere's disease.

PMID- 11528271
TI  - Endoscopic-assisted myringoplasty.
AB  - An improved myringoplasty technique utilizing fibrin glue and carried out through
      the external auditory canal was recently introduced. This endoscopic-assisted
      technique allows exquisite views and avoids blind surgical procedures, thereby
      expanding the indications for minimally invasive myringoplasty. This technique
      was applied to patients in whom, due to the curved external auditory canal, the
      margin of the perforation of the tympanic membrane was not visible with an
      operating microscope. We summarized the results of 22 endoscopic-assisted
      myringoplasties and concluded that this technique provides satisfactory results
      both in the success rate of perforation closure and in hearing outcome.

PMID- 11528272
TI  - Correlation between MRI findings and second-Look operation in cholesteatoma
      surgery.
AB  - Two-staged intact canal wall tympanoplasty is a common operation for treatment of
      middle ear cholesteatoma. MRI provides better tissue differentiation of the
      middle ear and/or mastoid, which often become occupied with soft density tissue
      after the first operation. If MRI was able to detect the presence of a recurrent
      or residual cholesteatoma with sufficient sensitivity and specificity, this may
      facilitate a decrease in the number of second-look procedures. This study
      compared MRI findings to surgical findings at second-look surgery and calculated
      the correlation rates between the two sets of findings. Thirty ears having
      undergone intact canal wall tympanoplasty for cholesteatoma at the initial
      operation were examined by MRI prior to the second look. Otoscopic findings of
      the tympanic membrane were nonsuspect in all cases. The true positive rate was
      11/30 (37%) and the true negative rate was 10/30 (33%), leading to a
      radiosurgical correlation of 70%, whereas the false positive rate was 6/30 (20%)
      and the false negative rate was 3/30 (10%). This indicates that 30% of the MRI
      findings were incorrect. Therefore, at the present time, MRI does not appear as a
      likely replacement for second-look surgery in cases of intact canal wall
      tympanoplasty.

PMID- 11528273
TI  - Treatment of gustatory sweating with botulinum toxin: special aspects.
AB  - Botulinum toxin treatment is an efficient, well-tolerated technique for patients
      suffering from gustatory sweating, first described by our group. With the
      experience gained in recent years we were able to improve on some of our skills
      in the diagnosis and treatment of gustatory sweating and here we wish to focus on
      some interesting aspects: (1) the necessity for an exact anamnesis before
      treatment with botulinum toxin to ensure correct treatment; (2) the advantages of
      Minor's test in special situations, for example, when sweating occurs in regions
      of hairy skin, retroauricular, at the back of the auricle and in areas distant
      from the site of salivary gland surgery; (3) the reduction of pain during
      treatment using an anesthetic ointment containing lidocaine and prilocaine as
      active substances; (4) intracutaneous injections in areas anterior to the fascia
      protected skin of the lateral face-covering mimetic muscles, and (5) the
      occasional necessity for short-time reinjection in small areas of persistent
      sweating.

PMID- 11528274
TI  - Treatment of snorers with a volatile oil: a randomized, double-blind placebo
      controlled trial.
AB  - Snoring is a significant problem both for the patient and for the bed partner.
      Seventy-two male and female heavy snorers and their bed partners participated in
      a double-blinded, placebo-controlled study on the effects of a volatile oil
      administered by gargling. The patients were diagnosed as heavy snorers after they
      underwent overnight polysomnography showing that their apnea indexes were below
      5, thus sleep apnea patients were not included in the study. The participants and
      their partners filled out evaluations concerning snoring intensity, mouth
      dryness, nasal stuffiness and the Epworth Sleepiness Scale prior to and after
      using the volatile oil or placebo for 14 consecutive nights. There were no
      statistically significant decreases in snoring as graded by the bed partner or in
      mouth dryness, nasal stuffiness, or the Epworth Sleepiness Scale scores graded by
      the patients who were randomized to use the volatile oil. The results of this
      study indicate that this volatile oil is not an effective treatment in patients
      presenting with symptoms of snoring.

PMID- 11528275
TI  - Voice outcome following lateral laryngotomy to remove teflon granuloma.
AB  - Formation of a Teflon granuloma may lead to progressive dysphonia and airway
      compromise. Excision of the granuloma by lateral laryngotomy allows preservation
      of the uninvolved lamina propria. A sternothyroid muscle flap or Silastic implant
      to medialize the vocal fold restores a straight glottal edge and optimizes voice
      production. Fifteen patients underwent removal of a Teflon granuloma via a
      lateral approach. Analysis of data revealed improved acoustic and aerodynamic
      parameters of voice following surgery. Indices of acoustic perturbation were
      reduced, and vocal pitch normalized. While the dynamic pitch range was unchanged,
      the capacity to vary loudness was enhanced. Flow rates in speech, abnormally
      elevated before surgery, normalized after the procedure, and phonation times were
      significantly longer. Perceptual and stroboscopic data confirmed that voices were
      improved, but not normal.

PMID- 11528276
TI  - [Fluorine-18]fluorodeoxyglucose positron emission tomography, DNA ploidy and
      growth fraction in squamous-cell carcinomas of the head and neck.
AB  - BACKGROUND: Positron emission tomography (PET) offers an opportunity to examine
      noninvasively cellular functions with different tracers.
      [(18)F]Fluorodeoxyglucose (FDG) is most commonly used in identifying malignant
      tumors. Several tumor biologic characteristics (tumor cell viability, growth
      faction, treatment response to radiation, cell membrane dysfunction, recurrence
      rate) are suggested to be characterized by [(18)F]FDG PET. The aim of this study
      was to assess which other tumor biologic characteristics of squamous-cell
      carcinoma of the head and neck are correlated with [(18)F]FDG PET. METHODS:
      [(18)F]FDG PET was performed in 14 patients with squamous-cell carcinomas of the
      upper digestive tract (TNM classification T(2)-T(4), N(1)-N(3)). After
      attenuation correction, predefined areas of the tumor were semiquantitatively
      analyzed by the technique of the region of interest and calculated as standard
      uptake values (SUV). Afterwards, 5 biopsies of different tumor regions were
      obtained during endoscopy in each patient under general anesthesia, and a
      correlation between SUV of [(18)F]FDG PET and tumor biologic parameters was
      attempted. These parameters included: quantitative DNA measurements (i.e. 2c
      deviation index, 5c exceeding rate), immunohistochemical assessment of growth
      fraction (i.e. Ki67-MIB-1, PCNA) along with morphological tumor front grading.
      RESULTS: The results revealed a marked variation of proliferation and cellular
      differentiation in various regions of the tumor for all parameters examined.
      There was a close correlation between [(18)F]FDG uptake and growth fraction (r =
      0.83 for Ki67-MIB-1 and r = 0.8 for PCNA). A poor correlation was found between
      DNA aneuploidy (r = 0.4) or tumor front grading (r = 0.12) and [(18)F]FDG uptake.
      CONCLUSIONS: Our results confirm previous clinical and histologic observations
      that squamous-cell carcinomas of the upper digestive tract are heterogeneous
      tumors. Ki67 antigen, which has been shown to be of predictive value for
      proliferation and individual prognosis, correlated with [(18)F]FDG uptake. Using
      [(18)F]FDG PET, the main proliferation centers of inhomogeneous squamous-cell
      carcinomas could be identified with possible clinical implications for patient
      management.

PMID- 11528277
TI  - Histological grading, growth fraction and DNA-ploidy as criteria for the
      treatment of pharyngeal and supraglottic squamous cell carcinomas: a preliminary,
      prospective study.
AB  - BACKGROUND: Individualized treatment for patients with squamous cell carcinomas
      is most desirable. Biologic parameters of tumors may provide relevant criteria to
      achieve this goal. The aim of this study was: (1) to avoid elective neck
      dissection in patients with squamous cell carcinomas of the pharynx and
      supraglottis staged N0 by ultrasonography; (2) to administer postoperative
      radiotherapy only in patients staged 'highly aggressive' by biologic tumor
      parameters, in order to reduce patient morbidity and to improve quality of life.
      STUDY DESIGN AND METHODS: This prospective trial was performed in 35 patients
      (any T stage, N0 or N1 by ultrasonographic examination). Tumor biopsies were
      taken for histological examination and for evaluation of some biological tumor
      markers. These parameters comprised DNA cytometric examinations, histological
      grading of the tumor front and immunohistochemical staining for proliferation
      markers (MIB1, PCNA). Based on these parameters, tumors were classified into 'low
      aggressive' (group 1) and highly aggressive (group 2) behavior. In all patients,
      second primaries were excluded by endoscopy, and the presenting tumor was
      resected with clear margins. In cases of ultrasonographically enlarged lymph
      nodes, functional neck dissection was performed. When biologic tumor profile
      showed low aggressive behavior (group 1), no postoperative radiotherapy was
      advised. In cases of highly aggressive tumors, radiotherapy was recommended
      postoperatively independent of all other parameters (group 2a and 2b). RESULTS:
      The average follow-up was 36 months (range 16-65 months). Fifteen patients were
      included in group 1, 20 patients in group 2. Three patients with highly
      aggressive tumors who refused RTx were regarded independently (group 2b). In this
      pilot study of 35 patients, there was no difference in disease-free survival
      between group 1 and group 2a. Twenty-five of 35 patients were alive with no
      evidence of disease 29-65 months after treatment (3 died of disease; 5 died of
      second primary carcinomas; 2 died independent of disease). Eleven of 15 patients
      survived disease free in group 1, 13/17 in group 2a. In group 2b, 2 out of 3
      patients, who were advised but refused postoperative radiotherapy, had
      recurrences. CONCLUSIONS: The results of this preliminary study point towards
      usefulness of some tumor biologic parameters in decision making for
      individualized treatment in patients with squamous cell carcinomas.

PMID- 11528278
TI  - Clinical outcome of laryngotracheal separation for intractable aspiration
      pneumonia.
AB  - OBJECTIVES: To confirm that laryngotracheal separation (LTS) is a satisfactory
      treatment for patients with intractable aspiration pneumonia, even though it does
      not require tracheoesophageal anastomosis. STUDY DESIGN: Retrospective. METHODS:
      Nine patients with intractable aspiration pneumonia underwent LTS at our
      institution from 1996 to 1999. Two patients underwent postoperative barium
      swallow radiography. RESULTS: Neither halitosis nor stimulation of the cough
      reflex occurred due to pooled secretions in the blind pouch of the proximal
      tracheal segment. Barium swallow radiography confirmed that the secretions
      drained within 40 min by swallowing or a change in patient position. CONCLUSION:
      LTS is a satisfactory solution to the problem of chronic aspiration. Neither
      pooled secretions in the proximal tracheal segment nor fistula formation were
      significant postoperative problems.

PMID- 11528280
TI  - Exercise and elderly persons.

PMID- 11528279
TI  - Inflammatory myositis: a rare differential diagnosis of a neck lump.
AB  - Inflammatory myositis is an extremely rare benign inflammatory condition of
      skeletal muscle. It usually affects the extremities, and there are only 10 cases
      reported in the head and neck region. Its significance is that in this region it
      can be clinically mistaken for a neoplasm. We describe a case and review the
      literature.

PMID- 11528281
TI  - Exercise in the geriatric population.

PMID- 11528282
TI  - Exercise therapy for older persons with cardiovascular disease.
AB  - Cardiac rehabilitation with exercise training after myocardial infarction in
      persons younger than 70 years has been found to cause a significant decrease in
      all-cause mortality, cardiovascular mortality, and fatal reinfarction, but no
      significant difference in nonfatal reinfarction. After myocardial infarction or
      coronary revascularization in older individuals, such programs significantly
      improve physical work capacity, body mass index, percent body fat, serum lipids,
      behavioral characteristics, and quality of life. Exercise modalities should
      include aerobic, resistance, and flexibility exercises. Less intense exercise of
      longer duration should be performed by older persons with coronary artery
      disease. Exercise training programs in patients with congestive heart failure
      produce significant improvement in peak oxygen consumption, exercise duration,
      and power output. The benefits of exercise training in patients with congestive
      heart failure may be due to an increase in cardiac output, an improvement in
      skeletal muscle metabolism, and an increase in peak blood flow to the exercising
      limb caused by a reduction in vascular resistance.

PMID- 11528283
TI  - Exercise in patients with hypertension.
AB  - A progressive increase in arterial stiffness with aging contributes to systolic
      hypertension that results in left ventricular hypertrophy and concentric
      remodeling in the elderly. Lowering of blood pressure in older adults reduces
      cardiovascular risks. Endurance exercise training can lower blood pressure in
      older adults with mild (grade I) hypertension. However, the blood pressure
      lowering effect of exercise training, compared with antihypertensive medications,
      is generally modest for both systolic and diastolic blood pressure. Exercise
      training alone is likely to be ineffective in lowering blood pressure
      sufficiently in older adults with moderate to severe (grade II and higher)
      hypertension. However, exercise and weight loss may potentiate the effects of
      antihypertensive medications in these subjects. Low-intensity endurance exercise
      training appears to be most effective in reducing blood pressure in older
      hypertensive adults. Metabolic adaptations to exercise training can significantly
      reduce other risk factors for coronary artery disease and atherosclerosis, in
      addition to reducing blood pressure. Endurance exercise training improves
      exercise capacity and quality of life, and can induce a modest but significant
      regression of left ventricular hypertrophy and remodeling in older adults with
      hypertension.

PMID- 11528284
TI  - The benefits of exercise in geriatric women.
AB  - Women 65 years of age and older are the fastest growing segment of the
      population. As women age, physical inactivity is the leading cause of morbidity
      and mortality due to coronary heart disease, diabetes mellitus, and hypertension.
      There is also a loss of both physiologic and psychological capabilities that
      contributes to an overall reduction in function and independent living. Regular
      physical activity in geriatric women has been shown to reduce cardiovascular
      morbidity and all-cause mortality. Further research needs to be done to evaluate
      the role of regular physical activity in the management of diabetes and
      hyperlipidemia.

PMID- 11528285
TI  - Exercise in the geriatric patient with congestive heart failure.
AB  - The benefits of exercise in the elderly patient with heart failure have been well
      documented, but the studies have been limited by restrictive inclusion criteria.
      Most studies have involved patients who are younger and healthier than those
      normally seen in clinical practice. Improvements in neurohormonal, metabolic, and
      vascular status have been well documented in the relatively young patients who
      have been evaluated. Consequently, peak exercise time, oxygen consumption,
      submaximal exercise, and quality of life have also improved. Studies suggest that
      older, more severely limited patients may also benefit from exercise. However,
      they are less likely to tolerate an exercise program and may not improve their
      quality of life if the exercise is excessive. Caution is warranted when exercise
      is prescribed to elderly patients with heart failure.

PMID- 11528286
TI  - Exercise in the healthy older adult.
AB  - Habitual exercise provides numerous health benefits to the older adult. While
      dynamic aerobic activities increase stamina and lung capacity, isometric or
      resistance training improves muscle strength and endurance. Long-term benefits of
      continued exercise include a decreased risk of death from heart disease, enhanced
      balance and mobility, a decreased risk of diabetes, and an improvement in
      depressive symptoms. While the hazards of exercise relate predominantly to
      extremes of intensity and duration, all older adults should consult with a
      physician before beginning a new activity program. A prescription for exercise
      should include both aerobic and resistance training components, and frequent
      follow-up to improve adherence is highly recommended.

PMID- 11528287
TI  - What I tell medical house staff about old hearts.
AB  - House officers tend to view elderly patients with heart disease in the same way
      they view middle-aged patients. This essay discusses the difference between old
      hearts and middle-aged hearts. The teaching setting, as well as the common
      cardiovascular problems seen in the elderly, are described in this essay. In
      addition, an explanation is given as to why the clinical picture of the same
      disease is different in elderly patients than in middle-aged patients.

PMID- 11528288
TI  - Ethical issues in the management of geriatric cardiac patients.
AB  - A nonterminally ill cardiac patient opts for a high-risk revascularization
      procedure but insists on not receiving cardiopulmonary resuscitation in the event
      of an iatrogenic cardiac arrest.

PMID- 11528289
TI  - Acquired left ventricular outflow tract obstruction during acute myocardial
      infarction: diagnosis of a new cardiac murmur.

PMID- 11528290
TI  - Atrial premature complexes with and without aberrant ventricular conduction.

PMID- 11528291
TI  - Ischemic stroke in elderly patients with symptomatic carotid stenosis.

PMID- 11528292
TI  - Atrial fibrillation in the elderly--an increasing problem that mandates
      aggressive management.

PMID- 11528293
TI  - Characterizing neurodynamic changes before seizures.
AB  - The study of dynamic changes in neural activity preceding epileptic seizure
      allows the characterization of a preictal state several minutes before seizure
      onset. This opens up new perspectives for studying the mechanisms of
      epileptogenesis as well as for possible therapeutic interventions, which
      represent a major breakthrough. In this review the authors present and discuss
      the results from their group in this domain using nonlinear analysis of brain
      signals, as well as the limitations of this topic and current questions.

PMID- 11528294
TI  - Nonlinear EEG analysis in epilepsy: its possible use for interictal focus
      localization, seizure anticipation, and prevention.
AB  - Several recent studies emphasize the high value of nonlinear EEG analysis
      particularly for improved characterization of epileptic brain states. In this
      review the authors report their work to increase insight into the spatial and
      temporal dynamics of the epileptogenic process. Specifically, they discuss
      possibilities for seizure anticipation, which is one of the most challenging
      aspects of epileptology. Although there are numerous studies exploring basic
      neuronal mechanisms that are likely to be associated with seizures, to date no
      definite information is available regarding how, when, or why a seizure occurs.
      Nonlinear EEG analysis now provides strong evidence that the interictal-ictal
      state transition is not an abrupt phenomenon. Rather, findings indicate that it
      is indeed possible to detect a preseizure phase. The unequivocal definition of
      such a state with a sufficient length would enable investigations of basic
      mechanisms leading to seizure initiation in humans, and development of adequate
      seizure prevention strategies.

PMID- 11528295
TI  - Epileptic event forewarning from scalp EEG.
AB  - The authors present a model-independent approach to quantify changes in the
      dynamics underlying nonlinear time-serial data. From time-windowed datasets, the
      authors construct discrete distribution functions on the phase space. Condition
      change between base case and test case distribution functions is assessed by
      dissimilarity measures via L1 distance and chi2 statistic. The discriminating
      power of these measures is first tested on noiseless data from the Lorenz and
      Bondarenko models, and is then applied to detecting dynamic change in
      multichannel clinical scalp EEG data. The authors compare the dissimilarity
      measures with the traditional nonlinear measures used in the analysis of chaotic
      systems. They also assess the potential usefulness of the new measures for
      robust, accurate, and timely forewarning of epileptic events.

PMID- 11528296
TI  - Understanding dynamic state changes in temporal lobe epilepsy.
AB  - The authors review their work in applying nonlinear dynamics to predict onset of
      seizures in patients with medically refractory temporal lobe epilepsy. The
      underlying mathematical methodology is presented in some detail. To illustrate
      their approach, they present an extensive discussion of the analysis of preictal
      data from two seizures of one patient, and from one disease-free subject. They
      find similar behavior in some nonlinear measures across seizures, which suggests
      the possibility of forming a robust method of seizure prediction. However,
      despite clinical and electrographic preictal and ictal similarity, they have also
      found marked heterogeneity in other nonlinear measures of preictal activity
      across seizures arising out of stage 2 nonrapid eye movement sleep. The
      underlying basis for this variation remains uncertain and needs to be the subject
      of further intense study to gain a better understanding of the dynamic basis of
      epilepsy. The origin of these heterogeneities may or may not be related to the
      much larger differences in nonlinear measures between patients and disease-free
      subjects. To understand these differences, the authors think it is crucial to pay
      close attention to potentially confounding factors such as behavioral and other
      state changes, and to study and report in detail the ways in which relevant
      nonlinear measures behave in the presence of such changes, independent of seizure
      onset.

PMID- 11528297
TI  - Early seizure detection.
AB  - For patients with medically intractable epilepsy, there have been few effective
      alternatives to resective surgery, a destructive, irreversible treatment. A
      strategy receiving increased attention is using interictal spike patterns and
      continuous EEG measurements from epileptic patients to predict and ultimately
      control seizure activity via chemical or electrical control systems. This work
      compares results of seven linear and nonlinear methods (analysis of power
      spectra, cross-correlation, principal components, phase, wavelets, correlation
      integral, and mutual prediction) in detecting the earliest dynamical changes
      preceding 12 intracranially-recorded seizures from 4 patients. A method of
      counting standard deviations was used to compare across methods, and the earliest
      departures from thresholds determined from non-seizure EEG were compared to a
      neurologist's judgement. For these data, the nonlinear methods offered no
      predictive advantage over the linear methods. All the methods described here were
      successful in detecting changes leading to a seizure between one and two minutes
      before the first changes noted by the neurologist, although analysis of phase
      correlation proved the most robust. The success of phase analysis may be due in
      part to its complete insensitivity to amplitude, which may provide a significant
      source of error.

PMID- 11528298
TI  - Observations on the application of the correlation dimension and correlation
      integral to the prediction of seizures.
AB  - The authors reexamine the correlation integral and the related correlation
      dimension in the context of EEG analysis with application to seizure prediction.
      They identify dependencies of the correlation integral and the correlation
      dimension on frequency and amplitude of the signal, which may result in a
      reinterpretation of the dynamic importance of these measures and may cast doubts
      on their predictive abilities for certain classes of seizures. The relevance, for
      clinical and research purposes, of the distinction between retrospective and
      prospective inference (prediction) is addressed briefly. The authors point to the
      need for further research, consisting of long time series, containing multiple
      seizures, and for the development of objective prediction criteria.

PMID- 11528299
TI  - Stochastic modeling and prediction of experimental seizures in Sprague-Dawley
      rats.
AB  - Most seizure prediction methods are based on nonlinear dynamic techniques, which
      are highly computationally expensive, thus limiting their clinical usefulness.
      The authors propose a different approach for prediction that uses a stochastic
      Markov chain model. Seizure (Ts) and interictal (Ti) durations were measured from
      11 rats treated with 3-mercaptopropionic acid. The duration of a seizure Ts was
      used to predict the time (Ti2) to the next one. Ts and Ti were distributed
      bimodally into short (S) and long (L), generating four probable transitions: S -
      > S, S --> L, L --> S, and L --> L. The joint probability density f (Ts, Ti2) was
      modeled, and was used to predict Ti2 given Ts. An identical model predicted Ts
      given the duration Ti1 of the preceding interictal interval. The median
      prediction error was 3.0 +/- 3.5 seconds for Ts (given Ti1) and 6.5 +/- 2.0
      seconds for Ti2 (given Ts). In comparison, ranges for observed values were 2.3
      seconds < Ts < 120 seconds and 6.6 seconds < Ti < 782 seconds. These results
      suggest that stochastic models are potentially useful tools for the prediction of
      seizures. Further investigation of the probable temporal interdependence between
      the ictal and interictal states may provide valuable insight into the dynamics of
      the epileptic brain.

PMID- 11528300
TI  - Markov process amplitude EEG model for spontaneous background activity.
AB  - The Markov process amplitude (MPA) EEG model effectively representing spontaneous
      brain activity of the EEG was introduced. The relationship between the electrical
      mechanism for EEG generation and the proposed model was also investigated. The
      MPA EEG model was described by the sinusoidal waves with the randomly fluctuating
      amplitude of the first-order Markov process. The parameters of the MPA EEG model
      were determined optimally based on the real EEG records. The results of model
      outputs in the frequency domain demonstrated an excellent fit with the power
      spectrum of the corresponding EEG. The simulated model signal in the time domain
      also showed good agreement with the EEG time series. The satisfactory results
      from the MPA EEG model suggest its possible applicability in clinical practice.
      Furthermore, from the high goodness of fit, the authors think that the neurons
      oscillate at fixed frequencies and are modulated by synaptic interactions in
      accordance with the first-order Markov process.

PMID- 11528302
TI  - The last word.

PMID- 11528301
TI  - Activation of interictal spiking in mesiotemporal lobe epilepsy by propofol
      induced sleep.
AB  - The objective of this study was to test whether low-dose propofol increases the
      number of interictal spikes in patients with mesiotemporal lobe epilepsy, and to
      determine whether this is the result of intrinsic properties and is restricted to
      the primary epileptogenic focus. Controlled infusion of propofol in step-up/-down
      target concentrations of 0, 0.3, 0.6, and 0.8 mg/L was administered to 10
      patients during a 3.5-hour daytime EEG registration. The number of spikes were
      counted and related to propofol concentration and sleep level. Results were
      compared with a spontaneous, nocturnal first sleep cycle in 9 of 10 patients. All
      patients entered nonrapid eye movement 1 sleep during propofol administration,
      and 8 reached nonrapid eye movement 2 sleep. In 7 patients who showed spikes,
      spikes were related to sleep (P < 0.05) and not to increasing (P = 0.1) or
      decreasing (P = 0.5) propofol concentration. Six of nine patients showed more
      spikes during spontaneous (nocturnal) sleep than during propofol-induced sleep.
      Contralateral spiking was not suppressed selectively. Low-dose propofol is a safe
      means of increasing spiking in these patients because it induces sleep. There
      were no signs of an intrinsic epileptogenicity of propofol or a selective effect
      on ipsilateral spikes. Controlled sleep induction will increase the yield of
      interictal spikes during short interictal recordings such as in
      magnetoencephalography.

PMID- 11528303
TI  - ECT education.

PMID- 11528304
TI  - Laboratory screening prior to ECT.
AB  - INTRODUCTION: Screening for occult disease using laboratory testing prior to
      electroconvulsive therapy (ECT) is a common practice with little empirical
      support. METHOD: In a pre-ECT and post-ECT sample of 73 and 562 (respectively)
      patients evaluated for ECT, the utility of the electrocardiogram, serum sodium,
      serum potassium, serum creatinine, chest radiograph, hemoglobin level, and white
      blood cell count was examined. RESULTS AND DISCUSSION: Reviewing the
      electrocardiogram and measuring sodium and potassium levels prior to the
      administration of ECT appear to be useful screening tests because they detect
      correctable unexpected conditions that are relevant to the risk of the procedure.
      Hemoglobin and white blood cell count abnormalities did not influence the
      administration of ECT or predict ECT complications. An abnormal creatinine level
      or abnormal chest radiograph prior to the administration of ECT predicted a poor
      medical prognosis that appeared largely unrelated to the administration of ECT.

PMID- 11528305
TI  - Phenylephrine and ECS-induced retrograde amnesia.
AB  - Phenylephrine is a nonselective alpha-receptor agonist. This study examined
      whether the administration of phenylephrine immediately before electroconvulsive
      shocks (ECS) attenuated ECS-induced retrograde amnesia. Adult male Wistar rats
      received phenylephrine (0.25 mg/kg i.p.) or saline 3 min before each of three
      once-daily true or sham ECS. Retention of pre-ECS learning was studied 1 day
      after the ECS course using a passive avoidance task. Phenylephrine increased
      seizure duration in ECS-treated rats, and also enhanced recall in both true and
      sham ECS groups. The latter finding suggests that phenylephrine nonspecifically
      improves cognitive functions, perhaps through adrenergic mechanisms that improve
      memory consolidation and storage. Since phenylephrine increases blood pressure,
      its cognitive effects also weaken the hypothesis that ECT-induced cognitive
      impairment results from the seizure-related hypertensive surge.

PMID- 11528306
TI  - Impact of maintenance ECT on concentration and memory.
AB  - INTRODUCTION: With the increased administration of outpatient electroconvulsive
      therapy (ECT), it is important to develop methods for monitoring patients for
      adverse effects of treatment. This pilot study was designed to evaluate the
      utility of using telephone assessments to determine whether patents receiving
      maintenance ECT (MECT) experience cognitive deficits related to individual
      treatments. METHOD: Patients were recruited from an existing population of
      outpatients receiving MECT. The consenting patients were called on three
      occasions and given a battery of telephone cognitive assessments including
      Orientation-Memory-Concentration, Buschke Selective Reminding, Verbal Fluency,
      "World" Backwards, Serial Sevens, and Wechsler Logical Memory. The occasions for
      the telephone interviews were the day before ECT, the day after a treatment, and
      a week later. RESULTS: Sixteen patients completed the study. The correlation
      between baseline and time 3 ranged from 1.00 for spelling "world" backward to
      0.509 for Verbal Fluency Category, indicating considerable variability in test
      retest reliability. One test, Verbal Fluency Category, showed group level
      effects, with decrements in performance the day after a treatment. One of the 16
      patients showed global cognitive deficits the day after a treatment. DISCUSSION:
      The pilot results suggest that telephone assessment may be a useful approach for
      monitoring patients receiving outpatient ECT. Monitoring may serve to guide
      clinicians in advising individuals and their caregivers about the return to
      activities after an individual treatment. Overall these findings support the
      tolerability of MECT.

PMID- 11528307
TI  - Focal prefrontal seizures induced by bilateral ECT.
AB  - INTRODUCTION: It has been proposed that the greater efficacy of bilateral (BL)
      over right unilateral (RUL) electroconvulsive therapy (ECT) at low stimulus
      intensity is due to differences in site of seizure initiation. We hypothesized
      that focal prefrontal seizures are more common with BL than RUL administration.
      METHOD: Records were reviewed of the 1,007 ECT treatments of 84 consecutive
      patients randomized to RUL or BL electrode placement. RESULTS: Eight events were
      identified in which there was an electroencephalographic seizure without motor
      manifestation. All of these events occurred at titration sessions and with BL
      stimuli (p = 0.002). These events were more likely to occur later in the course
      of treatment. DISCUSSION: We suggest that BL ECT may induce focal seizures in
      prefrontal areas and that these seizures are more likely to occur later in the
      treatment course.

PMID- 11528308
TI  - Long-term outcome after ECT for catatonic depression.
AB  - INTRODUCTION: This is the initial report of the course of major depression with
      catatonic features after hospitalization. METHOD: Telephone interviews and
      ratings were conducted 3-7 years after response to inpatient electroconvulsive
      therapy (ECT) for such catatonic depression. This was done for all 19 followable
      patients treated over a particular 4-year period. All had received left anterior
      right temporal brief-pulse ECT. Prior to data examination, we constructed rules
      to classify medications as antimelancholic. These rules led to the inclusion of
      lithium, tricyclics, bupropion, and venlafaxine in this antimelancholic
      classification and to the exclusion of selective serotonin reuptake inhibitors.
      RESULTS: Ten of the 13 patients discharged on antimelancholic medication (AMM)
      had good function on follow-up and no more than one rehospitalization. In
      contrast, none of the six patients in the other group had as good an outcome (p =
      0.004, corrected chi2 = 8.26). The AMM group had no deaths, but three patients in
      the other group died of acute cardiopulmonary causes (p = 0.015). In most cases,
      catatonia and depression were not identified by informant interview on follow-up.
      DISCUSSION: ECT followed by AMM usually led to long-term outcome that was good
      and better than without such medication. Although benzodiazepines can acutely
      diminish catatonia, we found no relevant long-term study; accordingly, long-term
      benzodiazepine use in catatonia is speculative.

PMID- 11528309
TI  - Effect on the emotions of healthy individuals of slow repetitive transcranial
      magnetic stimulation applied to the prefrontal cortex.
AB  - Recent studies indicate that both slow and fast repetitive transcranial magnetic
      stimulation (rTMS) have a mood-elevating effect in major depressive episodes. The
      effect of slow rTMS on the emotions of healthy individuals has not been examined.
      METHODS: We studied the effects of slow rTMS applied to the left and right
      prefrontal cortex (PFC) of 18 healthy individuals. Active and sham stimulation
      was applied to both sides of all individuals. Stimulation was with a 9-cm figure
      of-eight coil at the following parameters: 110% of motor threshold, 1 Hz, single
      train of 500 stimuli. Depression, happiness, irritability, and anxiety were
      measured before and 5, 30, and 240 min after stimulation using visual analogue
      scales. A sleep questionnaire was completed the morning after each stimulation
      session. A new method of providing sham was used. RESULTS: Slow rTMS applied to
      the PFC did not produce significant changes in the emotions of healthy
      individuals; nor was sleep influenced. DISCUSSION: In conclusion, slow rTMS at
      these parameters applied to the PFC does not produce significant changes in the
      emotions of healthy individuals.

PMID- 11528310
TI  - Factors influencing treatment frequency of continuation ECT in schizophrenia.
AB  - Although continuation and maintenance electroconvulsive therapy (C-ECT and M-ECT)
      have been used since 1943, no studies reported data that might help guide the
      selection of C-ECT frequency. This two-phase study was conducted in 32 chronic
      schizophrenic patients, with history of prior responsiveness to ECT to determine
      clinical variables associated with treatment frequency of C-ECT. After acute
      combination treatment with ECT and neuroleptics (Phase I), all patients received
      weekly ECT during the first 4 weeks of C-ECT (Phase II). They were then assigned
      to receive either weekly (n = 8) or biweekly (n = 24) ECT, depending on the
      history of their prior responsiveness to C-/M-ECT and their Brief Psychiatric
      Rating Scale (BPRS) scores. At the third month, patients with biweekly ECT were
      assigned to receive either biweekly (n = 17) or triweekly ECT (n = 7) following
      the same criteria. The duration of Phase II was 6 months. Onset of illness,
      numbers of admission, educational level, duration of trials of the previously
      failed neuroleptics, BPRS scores, and percentage of reductions in BPRS scores at
      the end of Phase I, Global Assessment of Functioning (GAF) scores at the end of
      Phase I, Mini-Mental State Exam (MMSE) scores at Phase I entry and Phase I end,
      and GAF and MMSE scores during the first month of Phase II showed a
      differentiation between patients having weekly treatment versus biweekly
      treatment. Whereas a history of previously failed flupenthixol treatment, dosage
      of flupenthixol used in this study, and MMSE scores at the end of Phase I and
      during the first month of Phase II showed a differentiation between patients
      having biweekly C-ECT versus triweekly C-ECT. Our results suggest that the better
      the prognostic factors for each patient, the longer the frequency of C-ECT.

PMID- 11528311
TI  - Magnetic and seizure thresholds before and after six electroconvulsive
      treatments.
AB  - OBJECTIVES: Electroconvulsive therapy (ECT) is a well-established treatment in
      psychiatry. It has been reported that in patients with nondelusional major
      depression, transcranial magnetic stimulation (TMS) may substitute for ECT. To
      explore whether ECT and TMS share mechanisms of action, we studied the effects of
      ECT on both seizure threshold (ST) and magnetic motor threshold (MT). METHODS: We
      measured ST and MT in 10 patients referred for ECT. MT was defined as the minimal
      power of the TMS equipment at which a motor evoked potential (MEP) response could
      be detected 50% of the time. ST was defined as the minimal intensity of
      electrical stimulation needed to elicit an adequate seizure. ECT was performed
      following the methods recommended by the American Psychiatric Association. All
      subjects signed an informed consent for participation in the research. RESULTS:
      We measured MT and ST in 10 patients before and after 6 ECT treatments. No
      changes in MT were detected from the treatment (paired t-test: t = 1.05, SD =
      4.78, p = 0.25). ST, on the other hand, increased significantly with treatment
      (paired t-test: t = 2.99, SD = 190.20, p < 0.001). CONCLUSIONS: ECT and TMS do
      not share a common mechanism at least with regard to MT and ST.

PMID- 11528312
TI  - Successful electroconvulsive therapy in an elderly man with severe
      thrombocytopenia: case report and literature review.
AB  - Electroconvulsive therapy (ECT) is a safe and effective treatment for depression.
      Furthermore, modifications to ECT have made it a safe procedure for patients who
      were previously thought to be too ill or old to undergo the stress of
      convulsions. Little is known, however, of the safety of performing ECT on
      patients with severe thrombocytopenia. Such patients may be at increased risk for
      hemorrhagic complications due to the procedure. In this article, we describe the
      case of a 74-year-old man with major depression and myelodysplastic syndrome with
      associated severe thrombocytopenia, who underwent successful administration of a
      full course (nine treatments) of ECT. The physiologic changes caused by modified
      ECT and the potential risk of hemorrhage (including intracranial hemorrhage) in
      thrombocytopenic patients undergoing ECT are also discussed.

PMID- 11528313
TI  - Emergence of catatonia during ECT.
AB  - Emergence of catatonia during electroconvulsive therapy (ECT) is unexpected, as
      catatonia responds well to ECT. We report four cases with onset of catatonia
      during ECT. Four inpatients with affective disorders (three without prior
      catatonia) developed catatonia by Bush-Francis criteria during a course of ECT.
      All four patients had been taking benzodiazepines, which were stopped 5-15 days
      before ECT. Two became catatonic after ECT no. 4, one after ECT no. 1, and one
      after ECT no. 10. The episodes of catatonia resolved promptly with the resumption
      of benzodiazepines. Two patients completed a course of ECT, whereas two received
      neuroleptics and/or antidepressants without further ECT. All showed improvements
      in their affective and psychotic symptoms. The cases illustrate the appearance of
      catatonia during a course of ECT and suggest recent cessation of benzodiazepines
      as a risk factor. Benzodiazepines relieve the catatonia, and ECT may be
      continued.

PMID- 11528314
TI  - Treatment of agitation and aggression in four demented patients using ECT.
AB  - Electroconvulsive therapy (ECT) has been shown to be effective in treating the
      behavioral symptoms associated with psychiatric disorders in demented patients.
      Four case studies are presented that show its efficacy in treating behavioral
      symptoms in demented patients. We suggest that ECT is beneficial in these
      potentially life-threatening behavioral disturbances.

PMID- 11528315
TI  - ECT in the treatment of status epilepticus.
AB  - INTRODUCTION: Owing to its potent anticonvulsant actions, electroconvulsive
      therapy (ECT) has been proposed as an intervention for treatment-resistant
      seizure disorders. METHOD: We review the literature on the use of ECT in
      treatment-resistant epilepsy and status epilepticus (SE) and present a case of a
      patient who was in nonconvulsive SE for 26 days and then treated with ECT after
      all standard pharmacological strategies were exhausted. Because of skull defects,
      a novel electrode placement was used. RESULTS: Owing to massively elevated
      seizure threshold attributable to concomitant anticonvulsant medications,
      extraordinarily high electrical dosage was needed for ECT to elicit generalized
      seizures. Status was terminated after three successful ECT-induced seizures.
      However, the long-term functional outcome of the patient was poor. DISCUSSION:
      The role of ECT in the treatment algorithm for SE is discussed.

PMID- 11528316
TI  - The combined use of bupropion, lithium, and venlafaxine during ECT: a case of
      prolonged seizure activity.
AB  - There is limited literature addressing the safety of administering
      electroconvulsive therapy (ECT) to patients concomitantly receiving bupropion
      monotherapy or in combination with other drugs that may alter the seizure
      threshold. We describe a prolonged seizure occurring during the first treatment
      of a course of ECT in an adult patient receiving long-term bupropion therapy,
      lithium, and venlafaxine.

PMID- 11528319
TI  - Modal ECT is effective: response to letter by Sackeim et al.

PMID- 11528317
TI  - Treatment of the modal patient: does one size fit nearly all?

PMID- 11528320
TI  - Response to Letter by Sackeim et al. " Treatment of the modal patient: does one
      size fit nearly all? ".

PMID- 11528321
TI  - Quantitative EEG during seizures induced by ECT.

PMID- 11528323
TI  - ECT and bilateral foot drop.

PMID- 11528324
TI  - Memory loss: from polarization to reconciliation.

PMID- 11528326
TI  - Unilateral ECT for prophylaxis in affective illness.

PMID- 11528327
TI  - Effect of propionyl-L-carnitine on exercise performance in peripheral arterial
      disease.
AB  - BACKGROUND: Supplementation with propionyl-L-carnitine (PLC) may be of use in
      improving the exercise capacity of people with peripheral arterial disease.
      METHODS: After a 2-wk exercise familiarization phase, seven subjects displaying
      intermittent claudication were studied over a 12-wk period consisting of three 4
      wk phases, baseline (B), supplementation (S), and placebo (P). PLC was
      supplemented at 2 g x d(-1), and subjects were blinded to the order of
      supplementation. Unilateral calf strength and endurance were assessed weekly.
      Walking performance was assessed at the end of each phase using an incremental
      protocol, during which respiratory gases were collected. RESULTS: Although there
      was not a significant increase in maximal walking time ( approximately 14%) in
      the whole group, walking time improved to a greater extent than the individual
      baseline coefficient of variation in four of the seven subjects. The changes in
      walking performance were correlated with changes in the respiratory exchange
      ratio both at steady state (r = 0.59) and maximal exercise (r = 0.79). Muscle
      strength increased significantly from 695 +/- 198 N to 812 +/- 249 N by the end
      of S. Changes in calf strength from B to S were modestly related to changes in
      walking performance (r = 0.56). No improvements in calf endurance were detected
      throughout the study. CONCLUSIONS: These preliminary data suggest that, in
      addition to walking performance, muscle strength can be increased in PAD patients
      after 4 wk of supplementation with propionyl-L-carnitine.

PMID- 11528328
TI  - Risk factors for groin injuries in hockey.
AB  - PURPOSE: The objective of this cohort study was to determine the level of off
      season sport specific activity, peak isometric adductor torque, and hip abduction
      flexibility that are predictive of groin or abdominal strain injury in the
      National Hockey League (NHL). METHODS: The subjects were 1292 consenting NHL
      players. Estimated relative risks of injury are reported using the following
      exposures: 1) level of sport specific training in the off-season, 2) peak
      isometric adductor torque, 3) total hip abduction flexibility, 4) previous
      injury, 5) years of NHL experience, and 6) skate blade hollow measurement.
      Estimates of probability of injury are predicted for various levels of exposures
      on the basis of logistic regression analysis. RESULTS: During training camp,
      players who reported less than 18 sessions sport specific training in the off
      season were at greater than three times the risk of injury than those who did not
      (relative risk (RR); 3.38 95% confidence interval (CI), 1.45-7.92). Players who
      reported previous history of this injury were at more than two times the risk of
      injury than those who did not (RR, 2.88; 95% CI, 1.33-6.26). Veterans were at
      greater than five times the risk of injury than rookies (RR, 5.69; 95% CI, 2.05
      15.85). Peak isometric adductor torque, total abduction flexibility, and skate
      blade hollow measurement were not predictive of injury. There is evidence of a
      dose-response gradient as predicted probability of injury decreases with
      increasing levels of sport specific training. In the regular season, sport
      specific training was not as strong a risk factor (RR, 2.32; 95% CI, 1.0-5.39).
      CONCLUSION: Low levels of off-season sport specific training and previous injury
      are clearly risks for groin injury at an elite level of hockey. Future research
      is required to investigate prevention strategies for this injury in hockey.

PMID- 11528329
TI  - Response to a fluid load in athletes with a history of exercise induced
      hyponatremia.
AB  - PURPOSE: To determine whether athletes who had previously developed hyponatremia
      during an ultradistance triathlon show an impaired ability to excrete a large
      fluid load compared with athletes who had completed the same race without
      developing hyponatremia. METHODS: Six athletes who had developed hyponatremia
      ([Na] < 135 mmol x L(-1)) in the 1997 Ironman Triathlon (study cases) were
      compared with six athletes who completed the same race without hyponatremia
      (controls). All participants consumed 3.4 L of water over 2 h at rest. Weight,
      urine output, urine electrolytes, serum [Na(+)], hemoglobin, and hematocrit were
      measured every 30 min. Changes in plasma volume and residual fluid volume in the
      gut were estimated from these data. RESULTS: There were no significant
      differences between cases and controls in any parameters measured. Maximal rates
      of urine production (+/- SD) (1043 +/- 331 mL x h(-1) for cases, 878 +/- 168 mL x
      h(-1) for controls) were substantially behind the rate of fluid intake (1500 mL x
      h(-1)). Consequent to fluid retention, serum [Na(+)] fell progressively in both
      groups. Five cases and four controls developed hyponatremia. There was an inverse
      correlation between change in body weight and change in [Na(+)] (r = -0.67).
      Estimated changes in the intra- and extra-cellular fluid volumes could account
      for all the retained fluid, and there was little evidence for fluid accumulation
      in the bowel. CONCLUSION: When evaluated at rest, there does not appear to be any
      unique pathophysiological characteristic that explains why some athletes develop
      hyponatremia in response to fluid overload during prolonged exercise. Rather,
      hyponatremia was induced with equal effect in both cases and controls, consequent
      to progressive fluid overload of all the body fluid compartments and without
      evidence for fluid retention in the small bowel.

PMID- 11528330
TI  - Long-term follow-up after exertional heat illness during recruit training.
AB  - PURPOSE: To evaluate long-term susceptibility to subsequent serious exertional
      heat illness (EHI) in military recruits who suffered exertional heat illness
      during basic training. METHODS: We identified Marine Corps members who completed
      at least 6 months of military service and suffered EHI treated as outpatients (N
      = 872) or inpatients (N = 50) during basic training in 1979-1991 at the Parris
      Island Marine Corps Recruit Depot, SC (EHI cases). We compared them to 1391
      similar members (noncases) who did not experience EHI during basic training.
      These subjects were followed from 6 months after accession into the military
      through the subsequent 4 yr. Follow-up was through military personnel records to
      determine retention and military hospital databases to determine subsequent
      hospitalizations during military service. RESULTS: Military retention rates were
      slightly lower for those who suffered EHI during basic training, compared with
      those who did not (24% vs 30% at 4 yr, respectively). Outpatient EHI cases also
      had about 40% higher subsequent hospitalization rates in military hospitals than
      noncases during their continued military service, although these differences
      declined over time and diagnoses showed little relationship to EHI. EHI cases had
      higher rates of subsequent hospitalization for EHI, but the number was too small
      (five hospitalizations) to provide stable comparisons. CONCLUSION:
      Hospitalization for EHI is uncommon during subsequent military service after an
      initial episode during basic training, and occurrence of EHI during basic
      training has only a small impact on subsequent military retention and
      hospitalization.

PMID- 11528331
TI  - Role of airway receptors in altitude-induced dyspnea.
AB  - PURPOSE: The purpose of this study was to examine the role of airway receptors in
      respiratory-related sensations after ascent to altitude. METHODS: Ratings of
      respiratory-related sensations, perceived exertion and acute mountain sickness,
      heart rate, and peripheral oxygen saturation were recorded at rest and exercise
      in male and female subjects who had inhaled either aerosolized saline or saline
      with tetracaine after acute ascent to an altitude of 3500 m and after prolonged
      acclimatization of 18 d at altitudes between 4000 and 5000 m. RESULTS: Tetracaine
      had no effect on respiratory-related sensations at altitude either at rest or
      during exercise, and male and female subjects experienced similar respiratory
      related sensations. Sensations of rapid breathing were experienced at rest after
      acute exposure to 3500 m as compared with sea level, but not after
      acclimatization to 5000 m. Sensations of rapid breathing, air hunger, and heavy
      breathing were experienced during exercise after acute and prolonged altitude
      exposure as compared with sea level, with a sensation of chest tightness
      experienced at 3500 m and a sensation of gasping experienced at 5000 m.
      CONCLUSION: These results suggest that airway afferents play no role in the
      respiratory-related sensations experienced by male and female subjects either
      during acute ascent to altitude or after prolonged acclimatization at altitude.

PMID- 11528332
TI  - Validation of the Hughston Clinic subjective knee questionnaire using gait
      analysis.
AB  - INTRODUCTION: Subjective questionnaires, completed by the patient, are often used
      to document the status of a disabled knee. The purpose of this study was to
      validate the Hughston Clinic subjective knee questionnaire by describing how knee
      kinematics and kinetics correlated to subjective knee scores after knee injury
      and surgery. METHODS: Five groups were studied: patients 2 (N = 37), 6 (N = 37),
      and 24 (N = 8) wk after ACL reconstruction (ACLR); patients with a chronic PCL
      deficiency (N = 9); and uninjured controls (N = 8). A three-dimensional motion
      analysis system and force platform were used to measure flexion angles and knee
      moments during level walking and stair climbing. RESULTS: Hughston Clinic
      questionnaire scores were significantly correlated to mechanical descriptors
      measured during stair ascent and descent in the 2- and 6-wk ACLR groups (P <
      0.05). The Hughston Clinic questionnaire score was correlated to several
      kinematic variables in the ACL reconstructed knee at 24 wk postoperative, e.g.,
      knee flexion during walking. In the PCL deficient group, the Hughston Clinic
      questionnaire score was correlated with several kinetic measures, e.g., the peak
      moment (knee extensors). The Hughston Clinic questionnaire score was not
      correlated to knee mechanics in the control group. CONCLUSION: The Hughston
      Clinic questionnaire score has been shown to be valid in this study as it
      reflects some mechanical descriptors during activities of daily living in the
      first 6 wk post ACL reconstruction. The questionnaire also provides information
      on gait modifications by people coping with knee injuries.

PMID- 11528333
TI  - Physiological responses to incremental exercise in patients with chronic fatigue
      syndrome.
AB  - PURPOSE: The purpose of this investigation was to characterize the physiological
      response profiles of patients with chronic fatigue syndrome (CFS), to an
      incremental exercise test, performed to the limit of tolerance. METHODS: Fifteen
      patients (12 women and three men) who fulfilled the case definition for chronic
      fatigue syndrome, and 15 healthy, sedentary, age- and sex-matched controls,
      performed an incremental progressive all-out treadmill test (cardiopulmonary
      exercise test). RESULTS: As a group, the CFS patients demonstrated significantly
      lower cardiovascular as well as ventilatory values at peak exercise, compared
      with the control group. At similar relative submaximal exercise levels (% peak
      VO(2)), the CFS patients portrayed response patterns (trending phenomenon)
      characterized, in most parameters, by similar intercepts, but either lower
      (VCO(2), HR, O(2pulse), V(E), V(T), PETCO(2)) or higher (B(f), V(E)/VCO(2))
      trending kinetics in the CFS compared with the control group. It was found that
      the primary exercise-related physiological difference between the CFS and the
      control group was their significantly lower heart rate at any equal relative and
      at maximal work level. Assuming maximal effort by all (indicated by RER,
      PETCO(2), and subjective exhaustion), these results could indicate either cardiac
      or peripheral insufficiency embedded in the pathology of CFS patients.
      CONCLUSION: We conclude that indexes from cardiopulmonary exercise testing may be
      used as objective discriminatory indicators for evaluation of patients
      complaining of chronic fatigue syndrome.

PMID- 11528334
TI  - Receptor changes in the nucleus tractus solitarii of the rat after exercise
      training.
AB  - PURPOSE: The aim of the present study was to evaluate neurotransmitter receptor
      changes in the nucleus tractus solitarii (NTS) of the rat after exercise
      training. METHODS: Twelve Wistar Kyoto rats were used. Six rats were submitted to
      a progressive training program in which they ran on a treadmill 5 d x wk(-1) for
      13 wk (trained). The other rats were kept as controls (sedentary). After this
      period, the rats were killed and the brains processed for quantitative receptor
      autoradiography. Coronal brain sections were obtained using a cryostat and were
      incubated with a specific buffer solution containing [(3)H]vasopressin or (3)Hp
      aminoclonidine. RESULTS: In the NTS of the trained rats, a decrease in the values
      of binding parameters (IC(50) and K(D)) of vasopressin receptors was observed,
      indicating an increase in the affinity of vasopressin receptors. On the other
      hand, a decreased affinity was observed for alpha(2)-adrenoceptors in the NTS of
      the trained rats in comparison with the sedentary animals. CONCLUSION: Exercise
      training leads to changes in vasopressin and alpha(2)-adrenoceptors, which may
      explain several physiological alterations occurring during physical activity.

PMID- 11528335
TI  - A comparison of the effects of unloading in young adult and aged skeletal muscle.
AB  - PURPOSE: The objective of this investigation was to determine whether
      morphological adaptations to unloading are different in young adult and aged
      skeletal muscle. METHODS: Sixteen young adult (8-month) Fischer 344 rats were
      randomly assigned to either a control or hindlimb suspension (HS) group. Sixteen
      aged (22-month) rats were similarly assigned to either control or HS conditions.
      After 4 wk, animals were euthanized and soleus and EDL muscles were
      histochemically analyzed. RESULTS: In controls, neither the soleus nor EDL
      displayed age-related differences in fiber size or composition. Unloading
      elicited fiber atrophy of the soleus in both age groups but to a greater extent
      (P < 0.05) in aged rats. Only in aged solei were HS-induced fiber type
      conversions (Type I --> II) detected. In the EDL, unloading caused atrophy only
      among the aged. CONCLUSION: These data suggest that aged muscle experiences
      greater detriment as a result of unloading. This may have important consequences
      in the aged because they are more likely to be restricted to bed rest or limb
      immobilization due to falls and other afflictions.

PMID- 11528336
TI  - Influence of training on NIRS muscle oxygen saturation during submaximal
      exercise.
AB  - PURPOSE: Endurance training improves the oxygen delivery and muscle metabolism.
      Muscle oxygen saturation measured by near infrared spectroscopy (IR-SO(2)), which
      is primarily influenced by the local delivery/demand balance, should thus be
      modified by training. We examined this effect by determining the influence of
      change in blood lactate and muscle capillary density with training on IR-SO(2) in
      seven healthy young subjects. METHODS: Two submaximal exercise tests at 50% (Ex1)
      and 80% pretraining VO(2max) (Ex2) were performed before and after a 4-wk
      endurance-training program. RESULTS: VO(2max) increased only slightly (+8%, NS)
      with training but the training effect was confirmed by the increased capillary
      density (+31%, P < 0.01) and citrate synthase activity (50%, P < 0.01),
      determined from muscle biopsy samples. Before training, blood lactate increased
      during the first 5 min of Ex1 and then remained constant (3.8 +/- 0.5 mmol x L(
      1), P < 0.01), whereas it increased continuously during Ex2 (8.9 +/- 1.8 mmol x
      L(-1), P < 0.001). After training, lactate decreased significantly and remained
      constant during the two bouts of exercise (2.0 +/- 0.4 and 3.7 +/- 1.2 at the end
      of Ex1 and Ex2, respectively, both P < 0.001). During Ex1, IR-SO(2) dropped
      initially at the onset of exercise and recovered progressively without reaching
      the resting level. Training did not change this pattern of IR-SO(2). During Ex2,
      IR-SO(2) decreased progressively during the 15 min of exercise (P < 0.05); IR-SO2
      kept constant after the initial drop after training. We found a significant
      relationship (r = 0.42, P = 0.03) between blood lactate and IR-SO(2) at the end
      of both bouts of exercise; this relationship was closer before training. By
      contrast, IR-SO(2) or IR-BV was not related to the capillary density. CONCLUSION:
      The training-induced adaptation in blood lactate influences IR-SO(2) during mild-
      to hard-intensity exercise. Thus, NIRS could be used as a noninvasive monitoring
      of training-induced adaptations.

PMID- 11528337
TI  - How long does the protective effect on eccentric exercise-induced muscle damage
      last?
AB  - PURPOSE: One bout of eccentric exercise produces an adaptation that reduces
      muscle damage in subsequent bouts. Because it is not known how long this
      adaptation lasts, the present study investigated the maximal length of the
      attenuated changes in muscle damage indicators after high-force eccentric
      exercise. METHODS: Male students (N = 35) were placed into three groups and
      performed two bouts of eccentric exercise of the nondominant elbow flexors
      separated by either 6 (N = 14), 9 (N = 11), or 12 (N = 10) months. Maximal
      isometric force (MIF), range of motion (ROM), upper arm circumference (CIR),
      muscle soreness (SOR), and plasma creatine kinase activity (CK) were measured
      before and for 5 d after exercise. Magnetic resonance (MR) images of the
      transverse and longitudinal scans of the upper arm were taken 4 d after exercise.
      Changes in the criterion measures were compared between the first and second
      bouts and between groups by a two-way repeated measures ANOVA. RESULTS: A faster
      recovery in MIF was evident after a second bout performed at 6 or 9 months, and
      reduced SOR as well as smaller increases in CIR, CK, and T2 relaxation time of MR
      images also occurred after the second exercise bout at 6 months compared with
      initial responses. No significant differences between the bouts were found for
      ROM, and the 12-month group did not show any repeated bout effect. CONCLUSION:
      These results show that the repeated bout effect for most of the criterion
      measures lasts at least 6 months but is lost between 9 and 12 months.

PMID- 11528338
TI  - Effects of endurance training on resting and post-exercise cardiac autonomic
      control.
AB  - PURPOSE: Endurance training induces reductions in both resting and postexercise
      heart rate (HR). If adaptation in cardiac autonomic regulation is a contributing
      factor in these reductions, changes in cardiac autonomic nervous system (ANS)
      should correspond to those in HR during an endurance-training program. We
      investigated the changes in resting and postexercise HR variabilities (both in
      the time and frequency domain) over a 6-wk training program. METHODS: HR
      variability was measured five times in an endurance-training group (N = 7) and
      four times in a control group (N = 5) during the course of study. RESULTS:
      Endurance training decreased HR and increased indices of parasympathetic
      modulation measured both at rest and during postexercise recovery periods.
      Noteworthy is that no changes in either HR or indices of ANS modulation measured
      during postexercise recovery periods were detectable after the first 7 d of the
      study despite continued changes in resting HR and indices in ANS modulation
      measured between the 7th and 42nd days of the endurance-training program.
      CONCLUSIONS: The study demonstrates that with endurance-training changes in
      cardiac ANS modulation partly contribute to a decrease in HR at rest and during
      postexercise recovery period, and that adaptation of the cardiac autonomic
      control occurs sooner in immediate postexercise periods than at rest.

PMID- 11528339
TI  - Atrioventricular plane displacement in female endurance athletes.
AB  - INTRODUCTION: A novel hypothesis for increased ventricular pumping describes the
      heart as a displacement pump, in which atrioventricular plane displacement (AVPD)
      is an important mechanism. The hypothesis predicts that AVPD increases at high
      heart rates. The aim of the present study was to determine whether AVPD increases
      during exercise at high heart rates. A secondary aim was to study the left
      ventricular function and dimensions in endurance-trained young female athletes.
      METHODS: Eight female cross-country skiers (18.5 +/- 0.9 yr, 169.3 +/- 2.9 cm,
      55.7 +/- 4.2 kg, and 64.8 +/- 3.7 mL x kg(-1) x min(-1) in maximal oxygen uptake)
      were compared with seven sedentary female controls (18.0 +/- 0.6 yr, 175.0 +/-
      2.5 cm, 71.1 +/- 4.1 kg, and 42.8 +/- 3.0 mL x kg(-1) x min(-1) in maximal oxygen
      uptake). Cardiac anatomy and function were assessed by echocardiography. RESULTS:
      Whereas left ventricular ejection fraction (LVEF) increased in both groups, AVPD
      fell significantly during exercise. AVPD did not correlate with LVEF, and there
      were no differences in AVPD between groups either at rest or during exercise.
      Cardiac output index (mL x lean body mass(-0.67)) and stroke volume index (mL x
      lean body mass(-1)) were higher in the trained group. The trained group had a
      larger left ventricular mass, and left ventricular internal dimensions, scaled to
      lean body mass. CONCLUSIONS: This first study to examine AVPD at rest and during
      exercise in endurance-trained athletes did not indicate that AVPD is an important
      mechanism of increased cardiac pumping during exercise. Endurance-trained female
      athletes have larger left ventricular dimensions and increased function as
      compared with sedentary subjects.

PMID- 11528340
TI  - Effects of short-duration and long-duration exercise on lipoprotein(a).
AB  - PURPOSE: Most studies that use either a single exercise session, exercise
      training, or a cross-sectional design have failed to find a relationship between
      exercise and plasma lipoprotein(a) [Lp(a)] concentrations. However, a few studies
      investigating the effects of longer and/or more strenuous exercise have shown
      elevated Lp(a) concentrations, possibly as an acute-phase reactant to muscle
      damage. Based on the assumption that greater muscle damage would occur with
      exercise of longer duration, the purpose of the present study was to determine
      whether exercise of longer duration would increase Lp(a) concentration and
      creatine kinase (CK) activity more than exercise of shorter duration. METHODS:
      Ten endurance-trained men (mean +/- SD: age, 27 +/- 6 yr; maximal oxygen
      consumption [VO(2max)], 57 +/- 7 mL x kg(-1) x min(-1)) completed two separate
      exercise sessions at 70% VO(2max). One session required 800 kcal of energy
      expenditure (60 +/- 6 min), and the other required 1500 kcal (112 +/- 12 min).
      Fasted blood samples were taken immediately before (0-pre), immediately after (0
      post), 1 d after (1-post), and 2 d after (2-post) each exercise session. RESULTS:
      CK activity increased after both exercise sessions (mean +/- SE; 800 kcal: 0-pre
      55 +/- 11, 1-post 168 +/- 64 U x L(-1) x min(-1); 1500 kcal: 0-pre 51 +/- 5, 1
      post 187 +/- 30, 2-post 123 +/- 19 U x L(-1) x min(-1); P < 0.05). However,
      median Lp(a) concentrations were not altered by either exercise session (800
      kcal: 0-pre 5.0 mg x dL(-1), 0-post 3.2 mg x dL(-1), 1-post 4.0 mg x dL(-1), 2
      post 3.4 mg x dL(-1); 1500 kcal: 0-pre 5.8 mg x dL(-1), 0-post 4.3 mg x dL(-1), 1
      post 3.2 mg x dL(-1), 2-post 5.3 mg x dL(-1)). In addition, no relationship
      existed between exercise-induced changes in CK activity and Lp(a) concentration
      (800 kcal: r = -0.26; 1500 kcal: r = -0.02). CONCLUSION: These results suggest
      that plasma Lp(a) concentration will not increase in response to minor exercise
      induced muscle damage in endurance-trained runners.

PMID- 11528341
TI  - Effects of a moderate glycemic meal on exercise duration and substrate
      utilization.
AB  - PURPOSE: To determine whether eating a breakfast cereal with a moderate glycemic
      index could alter substrate utilization and improve exercise duration. METHODS:
      Six active women (age, 24 +/- 2 yr; weight, 62.2 +/- 2.6 kg; VO(2peak), 46.6 +/-
      3.8 mL x kg(-1) x min(-1)) ate 75 g of available carbohydrate in the form of
      regular whole grain rolled oats (RO) mixed with 300 mL of water or water alone
      (CON). The trials were performed in random order and the meal or water was
      ingested 45 min before performing cycling exercise to exhaustion (60% of
      VO(2peak)). Blood samples were drawn for glucose, glucose kinetics, free fatty
      acids (FFA), glycerol, insulin, epinephrine (EPI), and norepinephrine (NE)
      determination. A muscle biopsy was obtained from the vastus lateralis muscle
      before the trial and immediately after exercise for glycogen determination.
      Glucose kinetics (Ra) were determined using a [6,6-(2)H] glucose tracer. RESULTS:
      Compared with CON, plasma FFA and glycerol levels were suppressed (P < 0.05)
      during the first 120 min of exercise for the RO trial. Respiratory exchange
      ratios (RER) were also higher (P < 0.05) for the first 120 min of exercise for
      the RO trial. At exhaustion, glucose, insulin, FFA, glycerol, EPI, NE, RER, and
      muscle glycogen were not different between trials. Glucose Ra was greater (P <
      0.05) during the RO trial compared with CON (2.36 +/- 0.22 and 1.92 +/- 0.27 mg x
      kg(-1) x min(-1), respectively). Exercise duration was 5% longer during RO, but
      the mean times were not significantly different (253.6 +/- 6 and 242.0 +/- 15
      min, respectively). CONCLUSIONS: Increased hepatic glucose output before fatigue
      provides some evidence of glucose sparing after the breakfast cereal trial.
      However, exercise duration was not significantly altered, possibly because of the
      sustained suppression of lipid metabolism and increased carbohydrate utilization
      throughout much of the exercise period.

PMID- 11528342
TI  - Influence of age on thirst and fluid intake.
AB  - Independently living older adults (over the age of 65 yr) consume adequate
      volumes of fluids on a daily basis. However, when challenged by fluid
      deprivation, a hyperosmotic stimulus, or exercise in a warm environment (all of
      which combine hypovolemia and hyperosmolality), older adults exhibit decreased
      thirst sensation and reduced fluid intake. Full fluid restoration eventually
      occurs, but full restoration of fluid balance is slowed. The aging process alters
      important physiological control systems associated with thirst and satiety.
      Recent evidence suggests that older men and women (i) have a higher baseline
      osmolality and thus a higher osmotic operating point for thirst sensation (with
      little or no change in sensitivity), and (ii) exhibit diminished thirst and
      satiety in response to the unloading (hypovolemia) and loading (hypervolemia) of
      baroreceptors. A diminished sensation of thirst in the elderly relative to young
      adults is generally absent when a volume stimulus is absent, despite higher
      baseline plasma osmolalities. Compared with the elderly, there are scant data
      associated with homeostatic control of thirst in children. Nonhomeostatic control
      of thirst and drinking behavior may likewise be different for children (as it is
      for the elderly), as compared with young adults; however, little empirical data
      exist on this topic. Children rarely exhibit voluntary dehydration for activities
      lasting 45 min or less; however, drink flavoring and sodium chloride are
      important promoters of drinking in active children.

PMID- 11528343
TI  - Effect of exercise on portal vein blood flow in man.
AB  - PURPOSE: Doppler pulsed flow and electronic scanning allow for instantaneous
      measurement of portal vein flow. This method was used to monitor alterations in
      splanchnic blood flow during exercise. METHODS: Measurements of portal vein blood
      flow were performed in eight healthy males at rest and at 10-min intervals during
      cycle ergometry at 70% of maximal aerobic capacity. Subjects stopped cycling
      briefly (approximately 30 s) and stopped breathing while measurements were made.
      Flow was calculated from values obtained for velocity of red blood cell passage
      and cross-sectional area of the vessel. RESULTS: Cross-sectional area decreased
      during exercise, resulting in a significant decrease in flow over time (P =
      0.0001 by ANOVA). The flow within the portal vein had decreased by 80% after 60
      min of exercise (absolute flow, 0.63 +/- 0.13 L x min(-1) at rest and 0.13 +/-
      0.04 L x min(-1) at 60 min). CONCLUSION: Electronic Doppler flow measurement of
      portal vein flow is a viable, noninvasive technique that can be used to measure
      splanchnic blood flow. Values obtained as a result of intensive exercise are in
      line with earlier results obtained with other techniques.

PMID- 11528344
TI  - Relation between intensity of physical activity and breast cancer risk reduction.
AB  - PURPOSE: To examine the influence of frequency, duration, and intensity of
      physical activity on risk of breast cancer and to compare breast cancer risks
      associated with self-reported versus assigned intensity levels of activity.
      METHODS: A population-based case-control study of 1233 incident breast cancer
      cases and 1241 controls was conducted in Alberta between 1995 and 1997. The
      frequency, duration and intensity of occupational, household, and recreational
      activities were measured throughout lifetime using the Lifetime Total Physical
      Activity Questionnaire and cognitive interviewing methods. Unconditional logistic
      regression analyses were used to estimate odds ratios and a full assessment of
      confounding and effect modification was undertaken. Odds ratios for self-reported
      and compendium-based assigned levels of activity were compared for lifetime total
      activity and by type of activity. RESULTS: Breast cancer risk reductions were
      comparable when self-reported and assigned intensity values were used, although
      the results and trends were more evident with the assigned intensity data.
      Moderate-intensity occupational and household activities decreased breast cancer
      risk, whereas recreational activity, at any intensity level, did not contribute
      to a breast cancer risk reduction. CONCLUSION: This study found that moderate
      intensity activities were the major contributors to the decrease in breast cancer
      risk found in this study and that risk reductions were more evident when the
      frequency and duration of activity alone were modeled. Of the three types of
      activity considered, the greatest risk reductions observed were for occupational
      and household activities.

PMID- 11528345
TI  - Delta efficiencies of running and cycling.
AB  - PURPOSE: The purpose of the present study was to compare delta efficiencies of
      running with cycling, while several factors that can possibly influence delta
      efficiency were excluded. METHODS: Twelve subjects performed a submaximal running
      and cycling test on subsequent days. Delta efficiencies of running and cycling
      were compared at equal metabolic intensities. Furthermore, rest periods were
      included in the protocol to avoid fatigue. Pedaling and stride frequencies were
      held constant during the tests. Finally, the influence of two ways of applying
      extra external load (inclination of treadmill and horizontal impeding forces) on
      the delta efficiency of running and cycling was investigated. RESULTS: The
      results of the present study show that the mean delta efficiency of running
      (45.5%) is still significantly higher than the mean delta efficiency of cycling
      (25.7%). The way extra external load is applied does not influence delta
      efficiency. CONCLUSION: The way of loading and the difference in metabolic
      intensity can be excluded as causes for the observed difference in delta
      efficiency between running and cycling. It is suggested that a different
      contribution in the metabolic load attributable to muscular activity of the arms
      and/or trunk that does not directly contribute to the work needed to overcome the
      amount of applied external load may be a relevant factor.

PMID- 11528346
TI  - Effects of technique variations on knee biomechanics during the squat and leg
      press.
AB  - PURPOSE: The specific aim of this project was to quantify knee forces and muscle
      activity while performing squat and leg press exercises with technique
      variations. METHODS: Ten experienced male lifters performed the squat, a high
      foot placement leg press (LPH), and a low foot placement leg press (LPL)
      employing a wide stance (WS), narrow stance (NS), and two foot angle positions
      (feet straight and feet turned out 30 degrees ). RESULTS: No differences were
      found in muscle activity or knee forces between foot angle variations. The squat
      generated greater quadriceps and hamstrings activity than the LPH and LPL, the WS
      LPH generated greater hamstrings activity than the NS-LPH, whereas the NS squat
      produced greater gastrocnemius activity than the WS squat. No ACL forces were
      produced for any exercise variation. Tibiofemoral (TF) compressive forces, PCL
      tensile forces, and patellofemoral (PF) compressive forces were generally greater
      in the squat than the LPH and LPL, and there were no differences in knee forces
      between the LPH and LPL. For all exercises, the WS generated greater PCL tensile
      forces than the NS, the NS produced greater TF and PF compressive forces than the
      WS during the LPH and LPL, whereas the WS generated greater TF and PF compressive
      forces than the NS during the squat. For all exercises, muscle activity and knee
      forces were generally greater in the knee extending phase than the knee flexing
      phase. CONCLUSIONS: The greater muscle activity and knee forces in the squat
      compared with the LPL and LPH implies the squat may be more effective in muscle
      development but should be used cautiously in those with PCL and PF disorders,
      especially at greater knee flexion angles. Because all forces increased with knee
      flexion, training within the functional 0-50 degrees range may be efficacious for
      those whose goal is to minimize knee forces. The lack of ACL forces implies that
      all exercises may be effective during ACL rehabilitation.

PMID- 11528347
TI  - Progressive strength training in sedentary, older African American women.
AB  - PURPOSE: This study investigated effects of an 8-wk, low-frequency and low
      volume, supervised, progressive strength training program emphasizing free
      weight, multijoint movements on the muscular power, strength, endurance, and
      flexibility of African American women 44 to 68 yr of age. METHODS: Nineteen
      sedentary African American women were randomly assigned to a strength training
      (ST) only group (N = 12; mean age, 51 yr) or a nonexercise control (C) group (N =
      7; mean age, 52 yr). Maximal power, strength, absolute endurance, and flexibility
      were assessed before and after training. Subjects trained 2 d x wk(-1) using free
      weight (barbells and dumbbells) and machine (plate loaded) exercises for two to
      three sets of 8 to 10 repetitions on both primary and assistance exercises.
      RESULTS: Upper body power (medicine ball put distance) significantly increased
      statistically (P = 0.002), but gains possibly lacked practical significance
      because of measurement variation. Lower body power (peak watts on bicycle)
      experienced a small, nonsignificant increase in the ST group. Significant
      increases (P = 0.000) in 1RM muscle strength occurred in the ST group (leg press,
      +99.8%; bench press, +34.4%). Absolute endurance significantly increased (P =
      0.000) in the ST group (leg press repetitions to failure at 70% pretest 1RM,
      +221%; bench press repetitions to failure at 50% pretest 1RM, +112%). Significant
      flexibility gains occurred in the ST group (sit-and-reach test, +8.2%; P =
      0.017). No significant changes occurred in power, strength, absolute endurance,
      or flexibility in the C group. CONCLUSION: This study demonstrates that 8 wk of
      low-frequency, supervised, progressive strength training emphasizing free weight,
      multijoint movements can safely cause significant gains in muscle strength,
      absolute endurance, and flexibility in older African American women.

PMID- 11528348
TI  - Maximal strength and power, endurance performance, and serum hormones in middle
      aged and elderly men.
AB  - PURPOSE: To examine maximal strength, power and muscle cross-sectional area,
      maximal and submaximal cycling endurance characteristics, and serum hormone
      concentrations of testosterone (T), free testosterone (FT), and cortisol (C) in
      middle-aged and elderly men. METHODS: Maximal knee extension force (isometric;
      MIF(KE)), power-load curves during concentric actions with loads ranging from 15%
      to 70% of 1 RM half-squat (1RM(HS)), muscle cross-sectional area of quadriceps
      femoris (CSA(QF)), workload, heart rate and lactate accumulation during
      incremental cycling, and serum hormone concentrations were measured in 26 middle
      aged (M42 yr) and 21 elderly men (M65 yr). RESULTS: The 1RM(HS) (14%), MIF(KE)
      (24%) and CSA(QF) (13%) were lower in M65 than in M42 (P < 0.05-0.01). Power
      during submaximal actions was lower (P < 0.05-0.001) in M65 than in M42, but the
      differences disappeared when expressed relative to CSA(QF). Serum FT was in M42
      higher (P < 0.05) than in M65. Maximal workload, maximal heart rate and peak
      blood lactate during cycling in M65 were 31%, 11%, and 20% lower than in M42 (P <
      0.01). During submaximal cycling blood lactate rose more rapidly with increasing
      workload in M65 than in M42 (P < 0.05-0.01), but the differences disappeared when
      expressed relative to CSA(QF). Significant correlations existed between
      individual values of serum FT:C ratio, C and T, and those of muscle strength and
      maximal workload. CONCLUSION: Declines in maximal strength, muscle mass, and
      endurance performance seem to take place with increasing age, although muscle
      power and demand for aerobic energy per unit of muscle tissue during submaximal
      loads remain similar. The balance between anabolic and catabolic hormones in
      aging people over the years may be associated with age-related decreased strength
      and declines in maximal cycling workload.

PMID- 11528349
TI  - Variability of competitive performance of distance runners.
AB  - PURPOSE: The typical variation in an athlete's performance from race to race sets
      a benchmark for assessing the utility of performance tests and the magnitude of
      factors affecting medal prospects. We report here the typical variation in
      competitive performance of endurance runners. METHODS: Repeated-measures analysis
      of log-transformed official race times provided the typical within-athlete
      variation in performance as coefficients of variation (CV). The types of race
      were cross-country runs (4 races over 9 wk), summer road runs (5 races over 4
      wk), winter road runs (4 races over 9 wk), half marathons (3 races over 13 wk and
      2 races over 22 wk), and marathons (2 races over 22 wk). RESULTS: Typical
      variation of times for the fastest quartile of male runners was 1.2-1.9% in the
      cross-country and road runs, 2.7% and 4.2% in half marathons, and 2.6% in
      marathons. Times for the slower half of runners in most events were more variable
      than those of the faster half (ratio of slower/faster CV, 1.0-2.3). Times of
      younger adult runners were more variable than times of older runners (ratio of
      younger/older CV, 1.1-1.8). Times of male runners were generally more variable
      than those of female runners (ratio of male/female CV, 0.9-1.7). CONCLUSION:
      Tests of endurance power suitable for assessing the smallest worthwhile changes
      in running performance for top runners need CV < or = 2.5% and < or = 1.5% for
      tests simulating half or full marathons and shorter running races, respectively.
      Most of the differences in variability of race times between types of race,
      ability groups, age groups, and sexes probably arise from differences in
      competitive experience and attitude toward competing.

PMID- 11528350
TI  - Validation of the Tracmor triaxial accelerometer system for walking.
AB  - PURPOSE: Walking is likely to contribute substantially to nonexercise activity
      thermogenesis. The Tracmor triaxial accelerometer system (Maastricht, The
      Netherlands) is the most widely validated system for detecting body movement in
      free-living subjects. The aim of this study was to validate the Tracmor triaxial
      accelerometer system for estimating the energy expenditure of walking. METHODS:
      Experiments were conducted in healthy subjects. First, baseline variability for
      Tracmor output was determined for subjects standing still. Second, Tracmor output
      was compared for walking on a treadmill and on level ground. Third, both Tracmor
      output and energy expenditure were compared for walking on a treadmill and
      walking on level ground. Finally, the effect of gradient on Tracmor output and
      energy expenditure was compared for subjects walking on a treadmill. RESULTS: The
      data demonstrated excellent reproducibility for comparing Tracmor output for
      standing (CV < 2%). There were excellent log-linear relationships between
      velocity and Tracmor output walking on a treadmill (r = 0.998) and on level
      ground (r = 0.999). Tracmor output and the energy expenditure of walking were
      inseparable for the two modalities of walking. However, the variance in response
      was such that to reliably derive the relationship between Tracmor output and
      energy expenditure, separate regression equations are needed for each subject.
      Finally, the Tracmor accelerometer did not detect the increased energy
      expenditure of walking that occurs as gradient increases. CONCLUSION: The Tracmor
      triaxial accelerometer provides reproducible and reliable data on the body motion
      associated with walking regardless of whether a subject walks on a treadmill or
      level ground. Tracmor units can be used to predict the energetic cost of walking
      provided that separate regression equations are derived for each subject to
      convert Tracmor output to energy expenditure.

PMID- 11528351
TI  - Physical activity and cardiovascular risk factors in a developing population.
AB  - PURPOSE: Noncommunicable diseases are emerging in developing countries. However,
      few studies have been conducted in those countries to evaluate the role of
      physical activity in the development of cardiovascular diseases. This study
      investigated physical activity and its relationship to risk factors for
      cardiovascular disease in a large population (N = 799) of civil servants from
      Benin City, Nigeria. METHODS: Physical activity levels were estimated by an
      interviewer-administered questionnaire, which determined the average hours per
      week over the past year spent in occupational and leisure activities. Time spent
      walking or biking to work was assessed as well. Other major measures included
      body mass index (BMI), waist-hip ratio (WHR), blood pressures, plasma insulin
      level, lipid profiles, and diet. RESULTS: More of the physical activity was
      attributed to occupational than to leisure activities. Compared with women, men
      had a higher activity level. No significant trend was observed across age groups.
      Male senior staff (a marker of higher socioeconomic status) had a lower physical
      activity level than male junior staff. Physical activity, especially time walking
      or biking to work, was inversely correlated with weight, BMI, WHR, blood
      pressures, insulin, total cholesterol, LDL and HDL cholesterol, and triglycerides
      in men, while such correlations were not consistent in women. In multivariate
      analysis in men, blood pressure and insulin were independently associated with
      BMI but not with walking, while an independent inverse association was seen
      between walking and BMI. CONCLUSION: Lack of physical activity was associated
      with adverse risk profiles for cardiovascular disease in this developing
      population.

PMID- 11528352
TI  - Comparison of the BOD POD with the four-compartment model in adult females.
AB  - PURPOSE: This study was designed to compare the accuracy and bias in estimates of
      total body density (Db) by hydrostatic weighing (HW) and the BOD POD, and percent
      body fat (%fat) by the BOD POD with the four-compartment model (4C model) in 42
      adult females. Furthermore, the role of the aqueous and mineral fractions in the
      estimation of body fat by the BOD POD was examined. METHODS: Total body water was
      determined by isotope dilution ((2)H(2)0) and bone mineral was determined by dual
      energy x-ray absorptiometry. Db and %fat were determined by the BOD POD and HW.
      The 4C model of Baumgartner was used as the criterion measure of body fat.
      RESULTS: HW Db (1.0352 g x cm(-3)) was not statistically different (P = 0.35)
      from BOD POD Db (1.0349 g x cm(-3)). The regression between Db by HW and the BOD
      POD significantly deviated from the line of identity (Db by HW = 0.90 x Db by BOD
      POD + 0.099; R(2) = 0.94). BOD POD %fat (28.8%) was significantly lower (P <
      0.01) than %fat by the 4C model (30.6%). The regression between %fat by the 4C
      model and the BOD POD significantly deviated from the line of identity (%fat by
      4C model = 0.88 x %fat by BOD POD + 5.41%; R(2) = 0.92). BOD POD Db and %fat
      showed no bias across the range of fatness. Only the aqueous fraction of the fat
      free mass (FFM) had a significant correlation with the difference in %fat between
      the 4C model and the BOD POD. CONCLUSION: These data indicate that the BOD POD
      underpredicted body fat as compared with the 4C model, and the aqueous fraction
      of the FFM had a significant effect on estimates of %fat by the BOD POD.

PMID- 11528353
TI  - Dietary soy and cardiovascular disease risk.

PMID- 11528354
TI  - Is weight an important factor in mortality risk in older women?

PMID- 11528355
TI  - Interactive effects of soy protein and estradiol on coronary artery reactivity in
      atherosclerotic, ovariectomized monkeys.
AB  - OBJECTIVE: Results of recent clinical trials indicate that mammalian estrogens
      may be less effective in reducing coronary heart disease risk than once thought.
      This study was designed to determine whether mammalian estrogen's coronary artery
      dilator benefits could be enhanced by adding soy with phytoestrogens. DESIGN:
      Forty-five atherosclerotic, ovariectomized monkeys were fed one of four diets:
      (1) atherogenic diet with casein/lactalbumin as source of protein (Casein, n =
      12); (2) casein diet with micronized estradiol equivalent to a woman's dose of 1
      mg/day (Casein + E2, n = 12); (3) atherogenic diet with soy protein with
      phytoestrogens (129 mg woman/day equivalent) (Soy, n = 11); and (4) the soy diet
      plus estradiol (Soy + E2, n = 10). METHODS: Quantitative angiography and
      intravascular Doppler were done after 6 months of experimental diet to measure
      changes in diameter and coronary flow reserve in the circumflex coronary artery
      in response to intracoronary acetylcholine and nitroglycerin. RESULTS: Arteries
      from the E2 and Soy + E2 groups dilated in response to acetylcholine 5 +/- 3% and
      12 +/- 5%, respectively (p < 0.05 vs. Casein). There was an interactive effect of
      soy and E2 on dilator response to acetylcholine (p < 0.05). Flow reserve was
      greatest in animals fed casein + E2 and soy + E2 (2.3 +/- 0.3 and 2.6 +/- 0.5,
      respectively; p < 0.05 vs. Casein). Soy protein alone had no effect on coronary
      artery reactivity (p > 0.05). CONCLUSION: Soy protein itself does not affect
      coronary artery dilator responses but interacts with estradiol to promote dilator
      responses to acetylcholine.

PMID- 11528356
TI  - The effect of menopause on the relation between weight gain and mortality among
      women.
AB  - OBJECTIVE: To examine the effect of menopause on the relation between weight gain
      and all-cause mortality. DESIGN: Prospective cohort study of 6,030 adults (ages
      25-82 years) who never smoked cigarettes, had no history of coronary heart
      disease, cancer, or stroke, and were enrolled in a 29-year follow-up in which
      anthropometric data were given at baseline and at 17 years after baseline.
      RESULTS: Weight gain that occurred over a 17-year interval (baseline to 17 years
      after baseline) increased the mortality risk of men and middle-aged women, but
      decreased the mortality risk of older women. Further study of the women revealed
      that a strong protective effect of weight gains was only evident among the
      leanest (<or=25 kg/m2) postmenopausal women. Specifically, weight gains of 10 kg
      or more (median = 13 kg) produced an almost threefold decrease in mortality risk
      among the leanest (<or=25 kg/m2) postmenopausal women [hazard ratio (HR) (95%
      confidence interval; CI) = 0.35 (0.13, 0.96)], but did not confer strong
      protection for heavier (>25 kg/m2) postmenopausal women [HR (95% CI) = 0.81
      (0.41, 1.58)] or for premenopausal women [HR (95% CI) = 1.05 (0.49, 2.25) for
      <or=25 kg/m2, 0.95 (0.38, 2.37) for >25 kg/m2]. We found that the protective
      effect of weight gain among the leanest postmenopausal women was primarily due to
      a more than threefold decrease in cardiovascular disease mortality risk. One
      possible explanation for these findings is that weight gain increases the level
      of adipose-tissue-derived estrogen among lean postmenopausal women. CONCLUSION:
      Moderate menopausal weight gain may be well tolerated in lean women.

PMID- 11528357
TI  - Unscheduled bleeding during initiation of continuous combined hormone replacement
      therapy: a direct comparison of two combinations of norethindrone acetate and
      ethinyl estradiol to medroxyprogesterone acetate and conjugated equine estrogens.
AB  - OBJECTIVE: To determine whether there are differences between continuous combined
      hormone replacement therapies on bleeding control. DESIGN: Nine hundred and forty
      five postmenopausal women were randomized to one of seven double-blind treatment
      groups (placebo, 0.25 mg norethindrone acetate (NA)/5 microg ethinyl estradiol
      (EE), 1 mg NA/5 microg EE, 0.5 mg NA/10 microg EE, 1 mg NA/10 microg EE, 5 microg
      EE, and 10 micro EE) or unmasked 0.625 mg conjugated equine estrogens (CEE)/2.5
      mg medroxyprogesterone acetate (MPA). Treatment was for 12 months; subjects kept
      daily diaries recording whether they had bleeding and/or spotting. RESULTS: The
      results focused on currently commercially available hormone replacement therapy
      products (femhrt [1 mg NA/5 microg EE] and Prempro [0.625 mg CEE/2.5 mg MPA]) as
      well as a high-dose NA/EE dose combination (1/10) over the first 6 months of use,
      the most critical period in establishing treatment adherence. At the end of month
      6 there was a greater incidence of amenorrhea with both NA/EE dose combinations
      compared with CEE/MPA (p = 0.009 for 1 mg NA/5 microg EE and p = 0.006 for 1 mg
      NA/10 microg EE). Statistically significantly more women were amenorrheic at
      every month based on cumulative amenorrhea for 1 mg NA/5 microg (p < 0.05)
      compared with CEE/MPA; at months 3 and 6 more women were amenorrheic on 1 mg
      NA/10 microg EE compared with CEE/MPA using the cumulative amenorrhea parameter.
      CONCLUSIONS: The results indicate that statistically significantly more women
      attained amenorrhea based on various parameters when administered continuous
      combined NA/EE compared with CEE/MPA. The potential for long-term treatment
      compliance based on better bleeding control may optimize the opportunity to
      prevent osteoporosis as well as other associated health benefits.

PMID- 11528358
TI  - Postmenopausal hormonal support: discontinuation of raloxifene versus estrogen.
AB  - OBJECTIVE: To determine possible differences in continuation among women
      initiating treatment with the selective estrogen receptor modulator raloxifene,
      versus those initiating treatment with estrogen-containing regimens. DESIGN: A
      pharmacy prescription database search for refill patterns. The study subjects
      were members of Kaiser Foundation Health Plan, a large health maintenance
      organization; 1,394 women age >or=60 years who filled index prescriptions for
      either raloxifene (n = 331) or systemic estrogens (n = 1,063) between April 1998
      and March 1999. The main outcome measure was discontinuation based on
      prescription refill patterns through December 2000. RESULTS: At 24 months, the
      probabilities of discontinuing were 56% for women starting raloxifene compared to
      72% for women starting estrogens. The likelihood of discontinuation was
      significantly less among women starting raloxifene than among those starting
      estrogen (hazard ratio = 0.75; 95% confidence interval = 0.64-0.88). Adjustments
      for age and prescriber specialty did not affect the risk. CONCLUSIONS: We
      conclude that discontinuation of estrogen by women well beyond the age of
      menopause is high; more than two-thirds discontinue within 2 years of starting.
      Women starting therapy with raloxifene are 25% percent less likely to discontinue
      their medication than those starting estrogen, providing some promise that long
      term benefits of raloxifene may be more easily achieved than those of estrogen.

PMID- 11528359
TI  - Red clover (Trifolium pratense) for menopausal women: current state of knowledge.
AB  - OBJECTIVE: Red clover (Trifolium pratense) extracts are becoming increasingly
      popular, primarily for the treatment of menopausal symptoms. Although promoted as
      a phytoestrogen source similar to soybeans, red clover is a medicinal herb, not a
      food, and traditionally has not been used long-term. We sought to review the
      scientific literature for this newer use. DESIGN: Medline was searched for
      controlled trials of red clover (Trifolium pratense), and other sources were
      searched for other studies and abstracts. RESULTS: Two double-blind placebo
      controlled trials found no beneficial effects of red clover extracts on hot
      flashes or other menopausal symptoms. Three of four trials examining the effect
      of red clover on lipids found no benefit; the fourth trial contains too little
      data to interpret. One study examining the effect of red clover on arterial
      compliance found a significant beneficial effect on arterial compliance.
      CONCLUSION: Red clover extracts have as yet no clear demonstrable benefit for
      menopausal symptoms. Potential estrogenic effects on breast and endometrium have
      not been adequately assessed. The presence of coumarins in some clover species
      makes it imperative to include tests of clotting factors in future trials.

PMID- 11528360
TI  - A double-blind randomized study on the effects of red clover isoflavones on the
      endometrium.
AB  - OBJECTIVE: To assess the effects of a red clover-derived isoflavone extract on
      the Ki-67 proliferative marker of endometrial biopsies in 45-to 50-year-old
      perimenopausal women. We hypothesized that we would be able to detect a decrease
      in the Ki-67 proliferative index during the late follicular phase after a 3-month
      course of approximately 50 mg red clover isoflavones. Isoflavones have been found
      to have some antiestrogenic effects, and an antiproliferative effect during the
      perimenopausal period may be especially useful owing to the excessive endometrial
      proliferation often characteristic of this period. DESIGN: In a double-blind,
      randomized, controlled study, 30 women between the ages of 45 and 50 years
      consented to an endometrial biopsy before and after a 3-month course of either
      placebo or active isoflavone extract. The biopsies were timed as close as
      possible to days 7-11 of the menstrual cycle, and simultaneous measurements of
      transvaginal endometrial thickness, uterine artery Doppler, hormone profiles,
      lipids, and bone markers were performed. RESULTS: Of 30 women, 2 did not return
      for a second biopsy, and a third had an unsuccessful second biopsy. Four subjects
      were excluded from the Intention to Treat analysis because they did not have a
      menstrual bleed within the time frame of the study (3 subjects) or were tested on
      day 13 instead of between days 7 and 11 of the cycle (1 subject). There was no
      change in the Ki-67 proliferation index after treatment in either group. Eight
      subjects in the placebo group and eight in the P-07 group had proliferative
      endometrial biopsies that were synchronized with estradiol levels at baseline and
      post-treatment, and analysis of these subjects revealed no detectable change in
      the relationship between estradiol levels and Ki-67 with treatment in either
      group. There was no change in fasting lipids, bone markers, uterine Doppler
      resistance, or pulsatility index. CONCLUSION: In this small pilot study, we did
      not find, using immunohistochemical quantification of the Ki-67 antigen, that red
      clover isoflavones had an antiproliferative effect in the endometrium. Small
      sample size, examination of a relatively short interval in the menstrual cycle,
      and isoflavone formulation may have contributed to our lack of findings; however,
      we believe that the issue of isoflavones and their possible antiproliferative
      effect is deserving of further study. A simpler physiological model with less
      hormonal variability, such as healthy, recently menopausal women on predetermined
      doses of estrogen, may prove to be more informative.

PMID- 11528361
TI  - Comparison of transdermal and oral estrogen-progestin replacement therapy:
      effects on cardiovascular risk factors.
AB  - OBJECTIVE: To determine the effects of oral and transdermal hormone replacement
      therapy on lipid profile and hemostatic factors in postmenopausal women. DESIGN:
      Twenty subjects were treated with oral E2 valerate (2 mg) combined with
      cyproterone acetate (1 mg) (group I) and 21 with transdermal E2 (1.5 mg) plus
      oral medroxyprogesterone acetate (5 mg) (group II). The effects on lipid profile
      and hemostatic parameters were evaluated at baseline and after 3, 6, and 12
      months of treatment. RESULTS: Group I showed a stronger increase of high-density
      lipoprotein (HDL) cholesterol levels (2-8%) and stronger reduction of atherogenic
      indices (total cholesterol/HDL cholesterol and low-density lipoprotein/HDL
      cholesterol) than group II. Group II showed a more pronounced reduction of
      triglyceride (21-31%) and factor VII (6-10%) levels than group I. Both groups
      showed reduced concentrations of total cholesterol, low-density lipoprotein
      cholesterol, tissue plasminogen activator, plasminogen activator inhibitor-1,
      antithrombin III, and protein S, whereas protein C was increased after 12 months
      of treatment. CONCLUSIONS: The cardioprotective effects of hormone replacement
      therapy are demonstrated by favorable effects on lipid profile and fibrinolytic
      activity. Oral hormone replacement therapy showed a more prominent effect on
      lipoprotein metabolism than did transdermal administration, but transdermal
      medication had a stronger effect on triglyceride and coagulation factors.
      However, it needs to be considered that there is an increased risk of venous
      thrombotic events in the first year of treatment.

PMID- 11528362
TI  - Pharmacokinetics and pharmacodynamics of 25-mg estradiol implants in
      postmenopausal Mexican women.
AB  - OBJECTIVE: To assess the serum concentrations of estradiol (E2), estrone (E1),
      gonadotrophins, sex hormone-binding globulin, and lipids, and to determine degree
      of symptom relief after subcutaneous implantation of 25 mg estradiol in
      postmenopausal Mexican women. DESIGN: Fifteen postmenopausal, hysterectomized
      women participated in an open, observational study. Blood samples were obtained
      before implantation and at regular intervals during a study period of 24 weeks.
      Climacteric symptoms were evaluated by means of the Greene climacteric scale.
      Wilcoxon's test was performed on the paired results of pre-and postimplantation
      values. RESULTS: Serum concentrations of E2 obtained after implantation were
      fairly constant, remaining within the early follicular range for the entire study
      period of 24 weeks, and were associated with significant symptom relief. A
      physiological, premenopausal E2:E1 ratio was achieved. No significant metabolic
      changes occurred. Side effects were estrogenic in nature and no removal of
      implant was required. CONCLUSIONS: Subcutaneous implantation of 25 mg estradiol
      results in physiological, premenopausal estrogen concentrations in most women and
      is associated with considerable symptom relief without inducing significant
      adverse metabolic effects.

PMID- 11528363
TI  - Women's responses to a mailed hormone replacement therapy workbook.
AB  - OBJECTIVE: Effectively communicating information about the complex decisions that
      face women at midlife, including whether to use hormone replacement therapy
      (HRT), is an ongoing challenge. Although numerous decision-making tools exist,
      few have been evaluated. The objective of this study was to examine women's use
      of a workbook designed to promote informed HRT decision-making. DESIGN: We
      developed a workbook to prepare women to discuss HRT, osteoporosis, heart
      disease, and breast cancer with their providers. To evaluate the workbook, women
      aged 45-65 years were randomly assigned to one of three groups: (1) workbook plus
      baseline and 6-month surveys, (2) workbook and 6-month survey, or (3) no workbook
      with both surveys. Results are based on the responses of 580 women in groups 1
      and 2 (response rate, 84.2%). RESULTS: At 6 months, 79% of women recalled
      receiving the workbook, of whom 51% read all or most of it, 35% skimmed or read
      part of it, and 14% did not read it. The percentages of women completing self
      assessments were 55% osteoporosis; 56% heart disease; 58% breast cancer; 57%
      advantages and disadvantages of HRT; and 52% personal preferences about HRT. As a
      result of the workbook, 10% made an appointment with their providers, and 12% had
      a discussion about HRT with their providers. Use of the workbook was not
      associated with menopause symptoms, attitudes about or use of HRT, hysterectomy,
      or provider discussions about menopause and HRT. CONCLUSION: This simple approach
      of using a mailed workbook holds promise as a successful mechanism to prepare
      women to discuss HRT and other related health issues with their providers.

PMID- 11528364
TI  - Adenomyosis demonstrates increased expression of the basic fibroblast growth
      factor receptor/ligand system compared with autologous endometrium.
AB  - OBJECTIVES: Basic fibroblast growth factor (bFGF) is an angiogenic growth factor
      present in human endometrium and myometrium. Women with leiomyoma-related
      abnormal uterine bleeding have local dysregulation of bFGF and its type 1
      receptor (FGF-R). This study was designed to evaluate if adenomyosis expresses
      bFGF and FGF-R, and if present, to compare bFGF and FGF-R expression in
      adenomyosis and autologous endometrium. DESIGN: Menopausal uteri containing
      endometrium and adenomyosis were analyzed using immunohistochemistry with
      monoclonal antibodies specific for bFGF, FGF-R, and proliferating cell nuclear
      antigen (PCNA), a marker of cellular proliferation. The expression and intensity
      of staining for bFGF, FGF-R, and PCNA were evaluated in the glandular epithelium
      and stroma of adenomyosis and endometrium. RESULTS: Glandular epithelial staining
      was significantly greater in adenomyosis compared with autologous endometrium for
      bFGF and FGF-R. Stromal staining for bFGF and PCNA was significantly increased in
      adenomyosis compared with autologous endometrium. CONCLUSIONS: Upregulation of
      the bFGF receptor/ligand system and increased cellular proliferation in
      adenomyosis may contribute to the pathogenesis of abnormal uterine bleeding
      associated with adenomyosis.

PMID- 11528365
TI  - Health beliefs and attitudes toward the prevention of osteoporosis in older
      women.
AB  - OBJECTIVE: A pilot study to determine health belief factors associated with
      osteoporosis prevention behaviors in peri-and postmenopausal women. DESIGN: We
      administered a survey to a convenience sample of 60 women aged 40-95 years old in
      an urban family practice center and an associated retirement community. The self
      reported questionnaire addressed demographics, osteoporosis risk factors, current
      preventive behaviors for osteoporosis, and health beliefs. RESULTS: The majority
      of women (89%) believed that osteoporosis is a serious condition, but only 29%
      perceived a personal susceptibility. Women were less concerned about osteoporosis
      when compared with cancer, cardiovascular disease, and neurologic disorders. Only
      40% of women were taking active measures to prevent osteoporosis. There was no
      significant relationship between active osteoporosis prevention behaviors and
      five health belief factors (motivation, barrier, active participant in health
      care, frustration, and benefit) (p >or= 0.43). However, active behaviors to
      prevent osteoporosis were found to correlate with the single item "I am worried
      about developing osteoporosis" (p = 0.03). Most women surveyed would be willing
      to exercise and take calcium and a multivitamin to prevent osteoporosis.
      CONCLUSION: Few women are taking active measures to prevent osteoporosis despite
      their belief that it is a serious condition. Our data suggest that most women do
      not perceive a personal susceptibility to the disease. Only women who reported
      actively worrying about developing osteoporosis were more likely to be engaged in
      significant osteoporosis preventive behaviors.

PMID- 11528366
TI  - Determinants of hormone replacement therapy duration among postmenopausal women
      with intact uteri.
AB  - OBJECTIVE: To investigate factors associated with hormone replacement therapy
      (HRT) duration among postmenopausal women with intact uteri. DESIGN: A Cox
      proportional hazard model on time to HRT discontinuation is estimated for 2,632
      postmenopausal HRT users with intact uteri who began a new episode of treatment
      between January 1990 and December 1994 in Saskatchewan, Canada. RESULTS: Major
      contraindicating medical events were highly associated with HRT discontinuation
      among postmenopausal women. Women who were diagnosed with uterine cancer while
      taking HRT were almost four times as likely to discontinue HRT, and women who
      were diagnosed with breast cancer while taking HRT were nearly five times as
      likely to discontinue HRT. Other statistically significant factors associated
      with the duration of HRT episodes include administration mode and the ability to
      try different types and strengths of HRT. Women initiating HRT with a transdermal
      patch were 50% more likely to discontinue it. Women who were willing and able to
      experiment with different HRT reduced their likelihood of discontinuing by one
      half to three-fourths. CONCLUSIONS: Although some of the factors associated with
      the hazard of HRT discontinuation among postmenopausal women who are taking the
      treatment for preventive benefits are immutable, clinicians may influence HRT
      continuation rates through initial drug choice or modifications in drug type or
      regimen over the course of therapy.

PMID- 11528367
TI  - Dietary inclusion of whole soy foods results in significant reductions in
      clinical risk factors for osteoporosis and cardiovascular disease in normal
      postmenopausal women.
AB  - OBJECTIVE: To determine the effects of dietary inclusion of soy foods on clinical
      markers for cardiovascular disease (CVD) and osteoporosis in normal
      postmenopausal women. DESIGN: This was a single open-group prospective clinical
      intervention. Forty-two normal postmenopausal women consumed three daily servings
      for 12 consecutive weeks of whole soy foods containing approximately 60 mg/d of
      isoflavones. Blood and urine specimens were obtained at baseline and after 12
      weeks of dietary intervention. RESULTS: Serum and urine levels of individual and
      total isoflavones increased significantly (7-19 fold, p < 0.001) from baseline. A
      significant increase (9.3%, p < 0.05) in the mean lag-time of low-density
      lipoprotein cholesterol oxidation was seen and was positively correlated with
      serum phytoestrogens (p < 0.05). Significant increases were found in mean levels
      of high-density lipoprotein cholesterol (HDLc) (3.7%, p < 0.05) and serum
      osteocalcin (10.2%, p < 0.025). Significant decreases were observed in total
      cholesterol:HDLc ratios (5.5%, p < 0.006) and mean urinary N-telopeptide
      excretion (13.9%, p < 0.02). Urinary excretion of total isoflavones was
      negatively correlated with very-low-density lipoprotein cholesterol,
      triglycerides, and total cholesterol:HDLc ratios (p < 0.04). No significant
      changes from baseline in HDLc peroxidation, total cholesterol, triglycerides, low
      density lipoprotein cholesterol, very-low-density lipoprotein cholesterol, bone
      specific alkaline phosphatase, follicle-stimulating hormone, or estradiol levels
      were observed. CONCLUSIONS: Dietary inclusion of whole soy foods containing 60
      mg/d of isoflavones results in significant serum levels of phytoestrogens and
      reductions in several key clinical risk factors for CVD and osteoporosis in
      normal postmenopausal women. Long-term, placebo-controlled clinical trials are
      needed to evaluate the effect of phytoestrogens on the clinical endpoints of CVD
      and osteoporosis in this population.

PMID- 11528368
TI  - Platelet function analyzer (PFA-100): a tool to quantify congenital or acquired
      platelet dysfunction.

PMID- 11528369
TI  - Relevance of folate metabolism in the pathogenesis of colorectal cancer.
AB  - The purpose of this review is to outline the principal mechanisms involved in
      folate metabolism and how they may relate to the pathogenesis of colorectal
      cancer (CRC). In recent years, mild folate depletion (low normal level) has been
      associated with an increased risk of developing certain cancers, in particular
      colorectal neoplasia. The epidemiologic and mechanistic evidence linking folate
      deficiency with carcinogenesis is reviewed, with a particular emphasis on
      colorectal neoplasia. Methylenetetrahydrofolate reductase (MTHFR) is a critical
      folate metabolizing enzyme, and a functional polymorphic variant of this enzyme,
      the so-called thermolabile variant, caused by a C677T transition in the MTHFR
      gene, is common in the general population. This review critically examines the
      evidence that suggests that carriers of this C677T variant may be at increased
      risk of developing colorectal neoplasia. Although folate depletion may predispose
      to the initiation of the neoplastic process, folate supplementation, on the other
      hand, might potentiate the progression of an already established early neoplastic
      clone (eg, a colorectal adenoma). This could have potential public health
      implications, given an increasingly widespread policy of folate supplementation
      of food staples.

PMID- 11528370
TI  - Inhibition of neuronal nitric oxide synthase ameliorates renal hyperfiltration in
      streptozotocin-induced diabetic rat.
AB  - Systemic inhibition of nitric oxide synthase (NOS) in streptozotocin-induced (STZ
      induced) diabetic rats results in decreases in glomerular filtration rate (GFR)
      and renal plasma flow (RPF) and an increase in renal vascular resistance (RVR).
      However, the exact isoform of NOS involved in diabetic renal hyperfiltration has
      not been determined. This study was conducted to clarify whether NO derived from
      neuronal NOS is involved in diabetic renal hyperfiltration when using a selective
      inhibitor of neuronal NOS, 7-nitro indazole (7-NI). Continuous infusion of NG
      nitro-L -arginine methyl ester (L-NAME) at 5 microg/kg/min ameliorated renal
      hyperfiltration, decreased RPF, and increased RVR in diabetic rats without
      affecting the mean arterial pressure (MAP). 7-NI administered intraperitoneally
      in diabetic rats significantly reduced GFR without affecting MAP, but the renal
      hyperfiltration was still observed after the administration of 7-NI. The combined
      administration of L-NAME after 7-NI caused a further decrease in GFR in diabetic
      rats and ultimately resulted in normalization of GFR. 7-NI did not change any
      parameters of renal hemodynamics in control rats. Urinary excretion of
      nitrite/nitrate and cyclic guanosine monophosphate was significantly increased in
      diabetic rats over values found in control rats. Our results suggested that a
      local inhibition of NO in the kidney was involved in the amelioration of diabetic
      renal hyperfiltration and that NO derived from neuronal NOS is involved, at least
      in part, in renal hyperfiltration in STZ-induced diabetic rats.

PMID- 11528372
TI  - Acquisition of the monocyte/macrophage phenotype in human mesangial cells.
AB  - The function of intrinsic glomerular cells in active glomerular inflammation may
      be similar to that of monocytes/macrophages. Mesangial cells have phagocytic
      properties and release numerous mediators. In this study we examined whether
      human mesangial cells (hMCs) express a monocyte/macrophage phenotype in active
      glomerular inflammation. We report that the proto-oncogene c-fms, the macrophage
      colony-stimulating factor (M-CSF) receptor, which is a characteristic gene of
      monocytes/macrophages, is expressed in hMCs. Normal unmanipulated hMCs express
      weak c-fms mRNA by reverse transcriptase-polymerase chain reaction (RT-PCR), and
      its expression increases after stimulation with platelet-derived growth factor-BB
      (PDGF-BB) and epidermal growth factor (EGF). The expression of c-fms was also
      demonstrated by flow cytometry with a specific polyclonal antibody. By
      immunohistochemistry, c-fms was prominently detected in acute glomerulonephritis,
      IgA nephritis, and lupus nephritis. These results indicate that hMCs express c
      fms in active glomerular inflammation and are consistent with mesangial cells
      acquiring some macrophage-like characteristics in diseased states.

PMID- 11528371
TI  - Epidermal growth factor induces expression of decay-accelerating factor in human
      colonic cancer cells via the mitogen-activated protein kinase pathway.
AB  - The expression of decay-accelerating factor (DAF), a complement regulatory
      protein, is enhanced in colorectal cancer. In this study, to elucidate mechanisms
      for enhanced DAF expression, we studied the effects of growth factors on DAF
      expression in HT-29 human colonic cancer cells. Cells were treated with epidermal
      growth factor (EGF), insulin-like growth factor-I, platelet-derived growth
      factor, and transforming growth factor-beta. DAF protein expression and mRNA
      expression were determined with enzyme immunoassay and Northern blot analysis.
      The signaling pathways that target DAF expression in response to growth factor
      stimulation were characterized by using various inhibitors of the signal
      transduction pathway. EGF induced significant increases in DAF protein and mRNA
      expression in HT-29 cells; the other growth factors had a weak effect or no
      effect. The EGF-induced DAF expression was inhibited by mitogen-activated protein
      (MAP) kinase kinase inhibitor PD 98059 but not by phosphatidylinositol-3 kinase
      inhibitor, phospholipase Cgamma inhibitor, or protein kinase C inhibitor. When we
      analyzed the phosphorylation state of the MAP kinase by immunoblot analysis,
      phosphorylated p44/p42 MAP kinase was detected in EGF-stimulated HT-29 cells, and
      the addition of PD 98059 abrogated the phosphorylation. These results indicate
      that EGF regulates DAF expression in HT-29 cells via the signaling pathway that
      depends on the activation of MAP kinase.

PMID- 11528373
TI  - Does a low-salt diet exert a protective effect on endothelial function in normal
      rats?
AB  - Sodium restriction is often used as an adjunct in the treatment of conditions
      characterized by endothelial dysfunction, such as hypertension and heart or
      kidney disease. However, the effect of sodium restriction on endothelial function
      is not known. Therefore, male Wistar rats were studied after a fixed salt diet
      had been maintained (low-salt group: 0.05% NaCl, n = 10; normal-salt group: 0.3%
      NaCl, n = 10) for 6 weeks. Blood pressure and sodium excretion values were
      measured once a week. Subsequently the rats were killed, the aorta was removed,
      and rings were cut. Endothelium-independent (sodium nitrite [SN]) and endothelium
      dependent (acetylcholine [ACh]) vasodilator responses were assessed in the
      presence of indomethacin (a cyclo-oxygenase inhibitor) and in the presence or
      absence of NG-monomethyl-L-arginine (L-NMMA; a competitive inhibitor of nitric
      oxide [NO] synthase). Endothelium-independent vasodilatation was not different
      for the two salt groups. Endothelium-dependent vasodilatation, on the other hand,
      was different. The response to ACh was almost completely abolished by L-NMMA in
      the normal-salt group, whereas vasodilatation was partially preserved during L
      NMMA in the low-salt group. Accordingly, the L-NMMA-sensitive contribution to ACh
      dependent vasodilatation was smaller in the low-salt group. Thus, salt
      restriction induced a non-NO and non-prostaglandin-dependent vasodilating
      pathway. By exclusion this could be endothelium-derived hyperpolarizing factor, a
      pathway of vasculoprotective potential. Accordingly, the relative contributions
      of the different vasoactive endothelial pathways were affected by salt intake.
      Further research will be needed to clarify the nature and importance of this non
      NO, non-prostaglandin-dependent pathway in the clinical setting as well.

PMID- 11528374
TI  - Lipoprotein lipase during continuous heparin infusion: tissue stores become
      partially depleted.
AB  - Lipoprotein lipase (LPL) and hepatic lipase (HL) are located at vascular surfaces
      in extrahepatic tissues and in the liver, respectively. Heparin displaces the
      enzymes into the circulating blood. Animal studies have shown that the liver
      takes up and degrades LPL. To explore whether heparin leads to a depletion of
      tissue stores, we followed the lipase activities in plasma during an 8-hour
      primed infusion of heparin in 10 healthy subjects. After an initial peak, the HL
      activity decreased slowly after a time curve similar to that for activated
      partial thromboplastin time. The time curve for LPL was different. After the
      initial peak, the activity dropped by almost 80%, from 30 to 120 minutes, and
      then leveled off to a plateau that corresponded to about 15% of the peak level. A
      second bolus of heparin was given to 4 subjects after 4 hours. The plasma LPL
      activity increased, but only to about 35% of the original peak level. We conclude
      that when heparin releases LPL into plasma, the lipase becomes liable to be taken
      up and degraded by the liver. After less than 1 hour, the stores of LPL have been
      exhausted, and recruitment of lipase into plasma depends on a slow but stable
      delivery of newly synthesized molecules.

PMID- 11528375
TI  - Something old, something new.

PMID- 11528376
TI  - A new verdict for an old convict.
AB  - Certain human cancers and carcinogen-induced rodent tumors commonly contain Kras2
      mutations. This activated form of ras has always been described as a dominant
      oncogene. A new study indicates that wildtype Kras2 has properties of a tumor
      suppressor gene and may have the capacity to reduce the transforming potential of
      oncogenically activated ras.

PMID- 11528377
TI  - The power of public access: the human genome project and the scientific process.
AB  - The scientific process, and scientific progress, require a critical examination
      of all published reports. Recent publications detailing errors in the draft human
      genome sequence are an integral part of our quest to better understand nature and
      demonstrate the value of free access to scientific data.

PMID- 11528378
TI  - Choreographing mRNA biogenesis.
AB  - Biogenesis of eukaryotic mRNA requires several post-transcriptional processing
      steps that must be completed accurately before it can be exported. Several
      processing factors are known to associate with RNA polymerase II during
      elongation, thereby positioning them to mediate efficient RNA processing. mRNAs
      are exported as complexes containing several RNA-binding proteins and other
      proteins. A recent study indicates that some of these packaging proteins also
      associate with RNA polymerase II during transcription. This suggests close
      coordination and mechanistic coupling of the events required to produce and
      export functional mRNAs.

PMID- 11528379
TI  - The sights along route 65.
AB  - Regeneration of rod visual pigments after photobleaching requires a protein
      called Rpe65. Several studies clarify its role in visual physiology and
      pathology, including a new one that shows it is required pigment regeneration in
      cone cells.

PMID- 11528382
TI  - How human geneticists in US view commercialization of the Human Genome Project.

PMID- 11528383
TI  - Mutations in SEPN1 cause congenital muscular dystrophy with spinal rigidity and
      restrictive respiratory syndrome.
AB  - One form of congenital muscular dystrophy, rigid spine syndrome (MIM 602771), is
      a rare neuromuscular disorder characterized by early rigidity of the spine and
      respiratory insufficiency. A locus on 1p35-36 (RSMD1) was recently found to
      segregate with rigid spine muscular dystrophy 1 (ref. 1). Here we refine the
      locus and find evidence of linkage disequilibrium associated with SEPN1, which
      encodes the recently described selenoprotein N (ref. 2). Our identification and
      analysis of mutations in SEPN1 is the first description of a selenoprotein
      implicated in a human disease.

PMID- 11528384
TI  - CARD15 mutations in Blau syndrome.
AB  - We have identified three missense mutations in the nucleotide-binding domain
      (NBD) of CARD15/NOD2 in four French and German families with Blau syndrome. Our
      findings indicate that, in addition to Crohn disease, CARD15 is involved in the
      susceptibility to a second granulomatous disorder.

PMID- 11528385
TI  - Human mtDNA and Y-chromosome variation is correlated with matrilocal versus
      patrilocal residence.
AB  - Genetic differences among human populations are usually larger for the Y
      chromosome than for mtDNA. One possible explanation is the higher rate of female
      versus male migration due to the widespread phenomenon of patrilocality, in which
      the woman moves to her mate's residence after marriage. To test this hypothesis,
      we compare mtDNA and Y-chromosome variation in three matrilocal (in which the man
      moves to his mate's residence after marriage) and three patrilocal groups among
      the hill tribes of northern Thailand. Genetic diversity in these groups shows a
      striking correlation with residence pattern, supporting the role of sex-specific
      migration in influencing human genetic variation.

PMID- 11528386
TI  - PTPRC (CD45) is not associated with the development of multiple sclerosis in U.S.
      patients.
AB  - A C-->G nucleotide transition in exon 4 of PTPRC (encoding protein-tyrosine
      phosphatase receptor-type C, also known as CD45) was recently reported to be
      genetically associated with the development of multiple sclerosis (MS). We
      performed an extensive evaluation of this polymorphism using large family-based
      and case-control comparisons. Overall, we observed no evidence of genetic
      association between the PTPRC polymorphism and MS susceptibility or disease
      course.

PMID- 11528387
TI  - Wildtype Kras2 can inhibit lung carcinogenesis in mice.
AB  - Although the ras genes have long been established as proto-oncogenes, the
      dominant role of activated ras in cell transformation has been questioned.
      Previous studies have shown frequent loss of the wildtype Kras2 allele in both
      mouse and human lung adenocarcinomas. To address the possible tumor suppressor
      role of wildtype Kras2 in lung tumorigenesis, we have carried out a lung tumor
      bioassay in heterozygous Kras2-deficient mice. Mice with a heterozygous Kras2
      deficiency were highly susceptible to the chemical induction of lung tumors when
      compared to wildtype mice. Activating Kras2 mutations were detected in all
      chemically induced lung tumors obtained from both wildtype and heterozygous Kras2
      deficient mice. Furthermore, wildtype Kras2 inhibited colony formation and tumor
      development by transformed NIH/3T3 cells and a mouse lung tumor cell line
      containing an activated Kras2 allele. Allelic loss of wildtype Kras2 was found in
      67% to 100% of chemically induced mouse lung adenocarcinomas that harbor a mutant
      Kras2 allele. Finally, an inverse correlation between the level of wildtype Kras2
      expression and extracellular signal-regulated kinase (ERK) activity was observed
      in these cells. These data strongly suggest that wildtype Kras2 has tumor
      suppressor activity and is frequently lost during lung tumor progression.

PMID- 11528388
TI  - Retinoic acid rescues inner ear defects in Hoxa1 deficient mice.
AB  - Little is known about the genetic pathways involved in the early steps of inner
      ear morphogenesis. Hoxa1 is transiently expressed in the developing hindbrain;
      its targeted inactivation in mice results in severe abnormalities of the otic
      capsule and membranous labyrinth. Here we show that a single maternal
      administration of a low dose of the vitamin A metabolite retinoic acid is
      sufficient to compensate the requirement for Hoxa1 function. It rescues cochlear
      and vestibular defects in mutant fetuses without affecting the development of the
      wildtype fetuses. These results identify a temporal window of susceptibility to
      retinoids that is critical for mammalian inner ear specification, and provide the
      first evidence that a subteratogenic dose of vitamin A derivative can be
      effective in rescuing a congenital defect in the mammalian embryo.

PMID- 11528389
TI  - Aberrant regulation of insulin receptor alternative splicing is associated with
      insulin resistance in myotonic dystrophy.
AB  - Myotonic dystrophy type 1 (DM1) is caused by a CTG trinucleotide expansion in the
      3' untranslated region of the DM protein kinase gene. People with DM1 have an
      unusual form of insulin resistance caused by a defect in skeletal muscle. Here we
      demonstrate that alternative splicing of the insulin receptor (IR) pre-mRNA is
      aberrantly regulated in DM1 skeletal muscle tissue, resulting in predominant
      expression of the lower-signaling nonmuscle isoform (IR-A). IR-A also
      predominates in DM1 skeletal muscle cultures, which exhibit a decreased metabolic
      response to insulin relative to cultures from normal controls. Steady-state
      levels of CUG-BP, a regulator of pre-mRNA splicing proposed to mediate some
      aspects of DM1 pathogenesis, are increased in DM1 skeletal muscle; overexpression
      of CUG-BP in normal cells induces a switch to IR-A. The CUG-BP protein mediates
      this switch through an intronic element located upstream of the alternatively
      spliced exon 11, and specifically binds within this element in vitro. These
      results support a model in which increased expression of a splicing regulator
      contributes to insulin resistance in DM1 by affecting IR alternative splicing.

PMID- 11528390
TI  - A Y-encoded subunit of the translation initiation factor Eif2 is essential for
      mouse spermatogenesis.
AB  - In mouse and man, deletions of specific regions of the Y chromosome have been
      linked to early failure of spermatogenesis and consequent sterility; the Y
      chromosomal gene(s) with this essential early role in spermatogenesis have not
      been identified. The partial deletion of the mouse Y short arm (the Sxrb
      deletion) that occurred when Tp(Y)1CtSxr-b (hereafter Sxrb) arose from
      Tp(Y)1CTSxr-b (hereafter Sxra) defines Spy, a Y chromosomal factor essential for
      normal spermatogonial proliferation. Molecular analysis has identified six genes
      that lie within the deletion: Ube1y1 (refs. 4,5), Smcy, Uty, Usp9y (also known as
      Dffry), Eif2s3y (also known as Eif-2gammay) and Dby10; all have closely similar X
      encoded homologs. Of the Y-encoded genes, Ube1y1 and Dby have been considered
      strong candidates for mouse Spy function, whereas Smcy has been effectively ruled
      out as a candidate. There is no Ube1y1 homolog in man, and DBY, either alone or
      in conjunction with USP9Y, is the favored candidate for an early spermatogenic
      role. Here we show that introduction of Ube1y1 and Dby as transgenes into Sxrb
      deletion mice fails to overcome the spermatogenic block. However, the
      introduction of Eif2s3y restores normal spermatogonial proliferation and
      progression through meiotic prophase. Therefore, Eif2s3y, which encodes a subunit
      of the eukaryotic translation initiation factor Eif2, is Spy.

PMID- 11528391
TI  - Comparable system-level organization of Archaea and Eukaryotes.
AB  - A central and long-standing issue in evolutionary theory is the origin of the
      biological variation upon which natural selection acts. Some hypotheses suggest
      that evolutionary change represents an adaptation to the surrounding environment
      within the constraints of an organism's innate characteristics. Elucidation of
      the origin and evolutionary relationship of species has been complemented by
      nucleotide sequence and gene content analyses, with profound implications for
      recognizing life's major domains. Understanding of evolutionary relationships may
      be further expanded by comparing systemic higher-level organization among
      species. Here we employ multivariate analyses to evaluate the biochemical
      reaction pathways characterizing 43 species. Comparison of the information
      transfer pathways of Archaea and Eukaryotes indicates a close relationship
      between these domains. In addition, whereas eukaryotic metabolic enzymes are
      primarily of bacterial origin, the pathway-level organization of archaeal and
      eukaryotic metabolic networks is more closely related. Our analyses therefore
      suggest that during the symbiotic evolution of eukaryotes, incorporation of
      bacterial metabolic enzymes into the proto-archaeal proteome was constrained by
      the host's pre-existing metabolic architecture.

PMID- 11528392
TI  - A mutant mitochondrial respiratory chain assembly protein causes complex III
      deficiency in patients with tubulopathy, encephalopathy and liver failure.
AB  - Complex III (CIII; ubiquinol cytochrome c reductase of the mitochondrial
      respiratory chain) catalyzes electron transfer from succinate and nicotinamide
      adenine dinucleotide-linked dehydrogenases to cytochrome c. CIII is made up of 11
      subunits, of which all but one (cytochrome b) are encoded by nuclear DNA. CIII
      deficiencies are rare and manifest heterogeneous clinical presentations. Although
      pathogenic mutations in the gene encoding mitochondrial cytochrome b have been
      described, mutations in the nuclear-DNA-encoded subunits have not been reported.
      Involvement of various genes has been indicated in assembly of yeast CIII (refs.
      8-11). So far only one such gene, BCS1L, has been identified in human. BCS1L
      represents, therefore, an obvious candidate gene in CIII deficiency. Here, we
      report BCS1L mutations in six patients, from four unrelated families and
      presenting neonatal proximal tubulopathy, hepatic involvement and encephalopathy.
      Complementation study in yeast confirmed the deleterious effect of these
      mutations. Mutation of BCS1L would seem to be a frequent cause of CIII
      deficiency, as one-third of our patients have BCS1L mutations.

PMID- 11528393
TI  - Mutant beta-spectrin 4 causes auditory and motor neuropathies in quivering mice.
AB  - The autosomal recessive mouse mutation quivering (qv), which arose spontaneously
      in 1953, produces progressive ataxia with hind limb paralysis, deafness and
      tremor. Six additional spontaneous alleles, qvJ, qv2J, qv3J, qv4J, qvlnd and
      qvlnd2J, have been identified. Ear twitch responses (Preyer's reflex) to sound
      are absent in homozygous qv/qv mice, although cochlear morphology seems normal
      and cochlear potentials recorded at the round window are no different from those
      of control mice. However, responses from brainstem auditory nuclei show abnormal
      transmission of auditory information, indicating that, in contrast to the many
      known mutations causing deafness originating in the cochlea, deafness in qv is
      central in origin. Here we report that quivering mice carry loss-of-function
      mutations in the mouse beta-spectrin 4 gene (Spnb4) that cause alterations in ion
      channel localization in myelinated nerves; this provides a rationale for the
      auditory and motor neuropathies of these mice.

PMID- 11528394
TI  - Mutations in the gene encoding epsilon-sarcoglycan cause myoclonus-dystonia
      syndrome.
AB  - The dystonias are a common clinically and genetically heterogeneous group of
      movement disorders. More than ten loci for inherited forms of dystonia have been
      mapped, but only three mutated genes have been identified so far. These are DYT1,
      encoding torsin A and mutant in the early-onset generalized form, GCH1 (formerly
      known as DYT5), encoding GTP-cyclohydrolase I and mutant in dominant dopa
      responsive dystonia, and TH, encoding tyrosine hydroxylase and mutant in the
      recessive form of the disease. Myoclonus-dystonia syndrome (MDS; DYT11) is an
      autosomal dominant disorder characterized by bilateral, alcohol-sensitive
      myoclonic jerks involving mainly the arms and axial muscles. Dystonia, usually
      torticollis and/or writer's cramp, occurs in most but not all affected patients
      and may occasionally be the only symptom of the disease. In addition, patients
      often show prominent psychiatric abnormalities, including panic attacks and
      obsessive-compulsive behavior. In most MDS families, the disease is linked to a
      locus on chromosome 7q21 (refs. 11-13). Using a positional cloning approach, we
      have identified five different heterozygous loss-of-function mutations in the
      gene for epsilon-sarcoglycan (SGCE), which we mapped to a refined critical region
      of about 3.2 Mb. SGCE is expressed in all brain regions examined. Pedigree
      analysis shows a marked difference in penetrance depending on the parental origin
      of the disease allele. This is indicative of a maternal imprinting mechanism,
      which has been demonstrated in the mouse epsilon-sarcoglycan gene.

PMID- 11528395
TI  - New views on RPE65 deficiency: the rod system is the source of vision in a mouse
      model of Leber congenital amaurosis.
AB  - Leber congenital amaurosis (LCA) is the most serious form of the autosomal
      recessive childhood-onset retinal dystrophies. Mutations in the gene encoding
      RPE65, a protein vital for regeneration of the visual pigment rhodopsin in the
      retinal pigment epithelium, account for 10-15% of LCA cases. Whereas previous
      studies of RPE65 deficiency in both animal models and patients attributed
      remaining visual function to cones, we show here that light-evoked retinal
      responses in fact originate from rods. For this purpose, we selectively impaired
      either rod or cone function in Rpe65-/- mice by generating double- mutant mice
      with models of pure cone function (rhodopsin-deficient mice; Rho-/-) and pure rod
      function (cyclic nucleotide-gated channel alpha3-deficient mice; Cnga3-/-). The
      electroretinograms (ERGs) of Rpe65-/- and Rpe65-/-Cnga3-/- mice were almost
      identical, whereas there was no assessable response in Rpe65-/-Rho-/- mice. Thus,
      we conclude that the rod system is the source of vision in RPE65 deficiency.
      Furthermore, we found that lack of RPE65 enables rods to mimic cone function by
      responding under normally cone-isolating lighting conditions. We propose as a
      mechanism decreased rod sensitivity due to a reduction in rhodopsin content to
      less than 1%. In general, the dissection of pathophysiological processes in
      animal models through the introduction of additional, selective mutations is a
      promising concept in functional genetics.

PMID- 11528396
TI  - Mutations in the gene encoding immunoglobulin mu-binding protein 2 cause spinal
      muscular atrophy with respiratory distress type 1.
AB  - Classic spinal muscular atrophy (SMA) is caused by mutations in the telomeric
      copy of SMN1. Its product is involved in various cellular processes, including
      cytoplasmic assembly of spliceosomal small nuclear ribonucleoproteins, pre-mRNA
      processing and activation of transcription. Spinal muscular atrophy with
      respiratory distress (SMARD) is clinically and genetically distinct from SMA.
      Here we demonstrate that SMARD type 1 (SMARD1) results from mutations in the gene
      encoding immunoglobulin micro-binding protein 2 (IGHMBP2; on chromosome 11q13.2
      q13.4). In six SMARD1 families, we detected three recessive missense mutations
      (exons 5, 11 and 12), two nonsense mutations (exons 2 and 5), one frameshift
      deletion (exon 5) and one splice donor-site mutation (intron 13). Mutations in
      mouse Ighmbp2 (ref. 14) have been shown to be responsible for spinal muscular
      atrophy in the neuromuscular degeneration (nmd) mouse, whose phenotype resembles
      the SMARD1 phenotype. Like the SMN1 product, IGHMBP2 colocalizes with the RNA
      processing machinery in both the cytoplasm and the nucleus. Our results show that
      IGHMBP2 is the second gene found to be defective in spinal muscular atrophy, and
      indicate that IGHMBP2 and SMN share common functions important for motor neuron
      maintenance and integrity in mammals.

PMID- 11528397
TI  - Disruption of an imprinted gene cluster by a targeted chromosomal translocation
      in mice.
AB  - Genomic imprinting is an epigenetic process in which the activity of a gene is
      determined by its parent of origin. Mechanisms governing genomic imprinting are
      just beginning to be understood. However, the tendency of imprinted genes to
      exist in chromosomal clusters suggests a sharing of regulatory elements. To
      better understand imprinted gene clustering, we disrupted a cluster of imprinted
      genes on mouse distal chromosome 7 using the Cre/loxP recombination system. In
      mice carrying a site-specific translocation separating Cdkn1c and Kcnq1,
      imprinting of the genes retained on chromosome 7, including Kcnq1, Kcnq1ot1,
      Ascl2, H19 and Igf2, is unaffected, demonstrating that these genes are not
      regulated by elements near or telomeric to Cdkn1c. In contrast, expression and
      imprinting of the translocated Cdkn1c, Slc22a1l and Tssc3 on chromosome 11 are
      affected, consistent with the hypothesis that elements regulating both expression
      and imprinting of these genes lie within or proximal to Kcnq1. These data support
      the proposal that chromosomal abnormalities, including translocations, within
      KCNQ1 that are associated with the human disease Beckwith-Wiedemann syndrome
      (BWS) may disrupt CDKN1C expression. These results underscore the importance of
      gene clustering for the proper regulation of imprinted genes.

PMID- 11528398
TI  - The UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase gene is
      mutated in recessive hereditary inclusion body myopathy.
AB  - Hereditary inclusion body myopathy (HIBM; OMIM 600737) is a unique group of
      neuromuscular disorders characterized by adult onset, slowly progressive distal
      and proximal weakness and a typical muscle pathology including rimmed vacuoles
      and filamentous inclusions. The autosomal recessive form described in Jews of
      Persian descent is the HIBM prototype. This myopathy affects mainly leg muscles,
      but with an unusual distribution that spares the quadriceps. This particular
      pattern of weakness distribution, termed quadriceps-sparing myopathy (QSM), was
      later found in Jews originating from other Middle Eastern countries as well as in
      non-Jews. We previously localized the gene causing HIBM in Middle Eastern Jews on
      chromosome 9p12-13 (ref. 5) within a genomic interval of about 700 kb (ref. 6).
      Haplotype analysis around the HIBM gene region of 104 affected people from 47
      Middle Eastern families indicates one unique ancestral founder chromosome in this
      community. By contrast, single non-Jewish families from India, Georgia (USA) and
      the Bahamas, with QSM and linkage to the same 9p12-13 region, show three distinct
      haplotypes. After excluding other potential candidate genes, we eventually
      identified mutations in the UDP-N-acetylglucosamine-2-epimerase/N
      acetylmannosamine kinase (GNE) gene in the HIBM families: all patients from
      Middle Eastern descent shared a single homozygous missense mutation, whereas
      distinct compound heterozygotes were identified in affected individuals of
      families of other ethnic origins. Our findings indicate that GNE is the gene
      responsible for recessive HIBM.

PMID- 11528399
TI  - An evaluation of the draft human genome sequence.
AB  - The completed draft version of the human genome, comprised of multiple short
      contigs encompassing 85% or more of euchromatin, was announced in June of 2000
      (ref. 1). The detailed findings of the sequencing consortium were reported
      several months later. The draft sequence has provided insight into global
      characteristics, such as the total number of genes and a more accurate definition
      of gene families. Also of importance are genome positional details such as local
      genome architecture, regional gene density and the location of transcribed units
      that are critical for disease gene identification. We carried out a series of
      mapping and computational experiments using a nonredundant collection of 925
      expressed sequence tags (ESTs) and sections of the public draft genome sequence
      that were available at different timepoints between April 2000 and April 2001. We
      found discrepancies in both the reported coverage of the human genome and the
      accuracy of mapping of genomic clones, suggesting some limitations of the draft
      genome sequence in providing accurate positional information and detailed
      characterization of chromosomal subregions.

PMID- 11528400
TI  - Rescue of embryonic lethality in Mdm4-null mice by loss of Trp53 suggests a
      nonoverlapping pathway with MDM2 to regulate p53.
AB  - The p53 protein can inhibit cell cycling or induce apoptosis, and is thus a
      critical regulator of tumorigenesis. This protein is negatively regulated by a
      physical interaction with MDM2, an E3 ubiquitin ligase. This interaction is
      critical for cell viability; loss of Mdm2 causes cell death in vitro and in vivo
      in a p53-dependent manner. The recently discovered MDM2-related protein MDM4
      (also known as MDMX) has some of the same properties as MDM2. MDM4 binds and
      inhibits p53 transcriptional activity in vitro. Unlike MDM2, however, MDM4 does
      not cause nuclear export or degradation of p53 (refs. 9,10). To study MDM4
      function in vivo, we deleted Mdm4 in mice. Mdm4-null mice died at 7.5-8.5 dpc,
      owing to loss of cell proliferation and not induction of apoptosis. To assess the
      importance of p53 in the death of Mdm4-/- embryos, we crossed in the Trp53-null
      allele. The loss of Trp53 completely rescued the Mdm4-/- embryonic lethality.
      Thus, MDM2 and MDM4 are nonoverlapping critical regulators of p53 in vivo. These
      data define a new pathway of p53 regulation and raise the possibility that
      increased MDM4 levels and the resulting inactivation of p53 contribute to the
      development of human tumors.

PMID- 11528401
TI  - Paternal transmission of the very common class I INS VNTR alleles predisposes to
      childhood obesity.
AB  - To identify some of the genetic factors that contribute to obesity in children of
      Central European and North African descent, we studied the parental transmission
      of alleles at the insulin locus to offspring with early-onset obesity. A variable
      nucleotide tandem repeat (VNTR) polymorphism upstream of the insulin gene (INS)
      is associated with variations in the expression of INS and the nearby gene
      encoding insulin-like growth factor 2 (IGF2). We found an excess of paternal
      transmission of class I VNTR alleles to obese children: children who inherited a
      class I allele from their father (but not those inheriting it from their mother)
      had a relative risk of early-onset obesity of 1.8. Due to the frequency of class
      I alleles in this population, this risk concerns 65-70% of all infants. These
      results suggest that increased in utero expression of paternal INS or IGF2 due to
      the class I INS VNTR allele may predispose offspring to postnatal fat deposition.

PMID- 11528405
TI  - Stretching the definition of espionage.

PMID- 11528406
TI  - Synaptic scaling in vitro and in vivo.

PMID- 11528408
TI  - Figure and ground in the brain.

PMID- 11528409
TI  - Protofibrils, the unifying toxic molecule of neurodegenerative disorders?

PMID- 11528411
TI  - Virtual neurology.

PMID- 11528410
TI  - Neuronal migration and the evolution of the human brain.

PMID- 11528412
TI  - From neuron to BOLD: new connections.

PMID- 11528414
TI  - Lactate enhances the acid-sensing Na+ channel on ischemia-sensing neurons.
AB  - Lactic acid produced by anaerobic metabolism during cardiac ischemia is among
      several compounds suggested to trigger anginal chest pain; however, the pH
      reached when a coronary artery is occluded (pH 7.0 to 6.7) can also occur during
      systemic acidosis, which causes no chest pain. Here we show that lactate, acting
      through extracellular divalent ions, dramatically increases activity of an acid
      sensing ion channel (ASIC) that is highly expressed on sensory neurons that
      innervate the heart. The effect should confer upon neurons that express ASICs an
      extra sensitivity to the lactic acidosis of local ischemia compared to acidity
      caused by systemic pathology.

PMID- 11528415
TI  - Opposing actions of protein kinase A and C mediate Hebbian synaptic plasticity.
AB  - A compartmental nerve-muscle tissue culture system expresses Hebbian activity
      dependent synapse modulation. Protein kinase C (PKC) mediates a heterosynaptic
      loss of efficacy, and we now show that protein kinase A (PKA) is involved in
      homosynaptic stabilization. Both work through postsynaptic changes in the
      acetylcholine receptor (AChR) as measured electrophysiologically and by imaging
      techniques.

PMID- 11528416
TI  - Reinforcing and locomotor stimulant effects of cocaine are absent in mGluR5 null
      mutant mice.
AB  - Both ionotropic and metabotropic glutamate receptors (mGluRs) are involved in the
      behavioral effects of pyschostimulants; however, the specific contributions of
      individual mGluR subtypes remain unknown. Here we show that mice lacking the
      mGluR5 gene do not self-administer cocaine, and show no increased locomotor
      activity following cocaine treatment, despite showing cocaine-induced increases
      in nucleus accumbens (NAcc) dopamine (DA) levels similar to wild-type (WT) mice.
      These results demonstrate a significant contribution of mGlu5 receptors to the
      behavioral effects of cocaine, and suggest that they may be involved in cocaine
      addiction.

PMID- 11528417
TI  - Synchrony does not promote grouping in temporally structured displays.
AB  - It has been proposed that the human visual system can use temporal synchrony to
      bind image regions into unified objects, as proposed in some neural models. Here
      we present experimental results from a new dynamic stimulus suggesting that
      previous evidence for this hypothesis can be explained with the well-established
      mechanisms of early visual processing, thus obviating the need to posit new
      synchrony-sensitive grouping mechanisms (see also ref. 5 for a critique of the
      binding by neural synchrony hypothesis).

PMID- 11528418
TI  - The fundamental plan of the retina.
AB  - The retina, like many other central nervous system structures, contains a huge
      diversity of neuronal types. Mammalian retinas contain approximately 55 distinct
      cell types, each with a different function. The census of cell types is nearing
      completion, as the development of quantitative methods makes it possible to be
      reasonably confident that few additional types exist. Although much remains to be
      learned, the fundamental structural principles are now becoming clear. They give
      a bottom-up view of the strategies used in the retina's processing of visual
      information and suggest new questions for physiological experiments and modeling.

PMID- 11528419
TI  - The 'Arctic' APP mutation (E693G) causes Alzheimer's disease by enhanced Abeta
      protofibril formation.
AB  - Several pathogenic Alzheimer's disease (AD) mutations have been described, all of
      which cause increased amyloid beta-protein (Abeta) levels. Here we present
      studies of a pathogenic amyloid precursor protein (APP) mutation, located within
      the Abeta sequence at codon 693 (E693G), that causes AD in a Swedish family.
      Carriers of this 'Arctic' mutation showed decreased Abeta42 and Abeta40 levels in
      plasma. Additionally, low levels of Abeta42 were detected in conditioned media
      from cells transfected with APPE693G. Fibrillization studies demonstrated no
      difference in fibrillization rate, but Abeta with the Arctic mutation formed
      protofibrils at a much higher rate and in larger quantities than wild-type (wt)
      Abeta. The finding of increased protofibril formation and decreased Abeta plasma
      levels in the Arctic AD may reflect an alternative pathogenic mechanism for AD
      involving rapid Abeta protofibril formation leading to accelerated buildup of
      insoluble Abeta intra- and/or extracellularly.

PMID- 11528420
TI  - Allosteric interaction between the amino terminal domain and the ligand binding
      domain of NR2A.
AB  - Fast desensitization is an important regulatory mechanism of neuronal NMDA
      receptor function. Only recombinant NMDA receptors composed of NR1/NR2A exhibit a
      fast component of desensitization similar to neuronal NMDA receptors. Here we
      report that the fast desensitization of NR1/NR2A receptors is caused by ambient
      zinc, and that a positive allosteric interaction occurs between the extracellular
      zinc-binding site located in the amino terminal domain and the glutamate-binding
      domain of NR2A. The relaxation of macroscopic currents reflects a shift to a new
      equilibrium due to increased zinc affinity after binding of glutamate. We also
      show a similar interaction between the ifenprodil binding site and the glutamate
      binding site of NR1/NR2B receptors. These data raise the possibility that there
      is an allosteric interaction between the amino terminal domain and the ligand
      binding domain of other glutamate receptors. Our findings may provide insight
      into how zinc and other extracellular modulators regulate NMDA receptor function.

PMID- 11528421
TI  - Two new classes of conopeptides inhibit the alpha1-adrenoceptor and noradrenaline
      transporter.
AB  - Cone snails use venom containing a cocktail of peptides ('conopeptides') to
      capture their prey. Many of these peptides also target mammalian receptors, often
      with exquisite selectivity. Here we report the discovery of two new classes of
      conopeptides. One class targets alpha1-adrenoceptors (rho-TIA from the fish
      hunting Conus tulipa), and the second class targets the neuronal noradrenaline
      transporter (chi-MrIA and chi-MrIB from the mollusk-hunting C. marmoreus). rho
      TIA and chi-MrIA selectively modulate these important membrane-bound proteins.
      Both peptides act as reversible non-competitive inhibitors and provide
      alternative avenues for the identification of inhibitor drugs.

PMID- 11528422
TI  - GABA(A) receptor cell surface number and subunit stability are regulated by the
      ubiquitin-like protein Plic-1.
AB  - Controlling the number of functional gamma-aminobutyric acid A (GABA(A))
      receptors in neuronal membranes is a crucial factor for the efficacy of
      inhibitory neurotransmission. Here we describe the direct interaction of GABA(A)
      receptors with the ubiquitin-like protein Plic-1. Furthermore, Plic-1 is enriched
      at inhibitory synapses and is associated with subsynaptic membranes.
      Functionally, Plic-1 facilitates GABA(A) receptor cell surface expression without
      affecting the rate of receptor internalization. Plic-1 also enhances the
      stability of intracellular GABA(A) receptor subunits, increasing the number of
      receptors available for insertion into the plasma membrane. Our study identifies
      a previously unknown role for Plic-1, a modulation of GABA(A) receptor cell
      surface number, which suggests that Plic-1 facilitates accumulation of these
      receptors in dendritic membranes.

PMID- 11528423
TI  - Subunit-specific temporal and spatial patterns of AMPA receptor exocytosis in
      hippocampal neurons.
AB  - Using a thrombin cleavage assay in cultured hippocampal neurons, we studied the
      kinetics, regulation and site of AMPA receptor surface delivery. Surface
      insertion of the GluR1 subunit occurs slowly in basal conditions and is
      stimulated by NMDA receptor activation and insulin, whereas GluR2 exocytosis is
      constitutively rapid. Although both subunits ultimately concentrate in synapses,
      GluR1 and GluR2 show different spatial patterns of surface accumulation,
      consistent with GluR1 being inserted initially at extrasynaptic sites and GluR2
      being inserted more directly at synapses. The spatiotemporal pattern of surface
      accumulation is determined by the cytoplasmic tails of GluR subunits, and in
      heteromeric receptors, GluR1 acts dominantly over GluR2. We propose that GluR1
      controls the exocytosis and GluR2/3, the recycling and endocytosis of AMPA
      receptors.

PMID- 11528424
TI  - Normal breathing requires preBotzinger complex neurokinin-1 receptor-expressing
      neurons.
AB  - The normal breathing rhythm in mammals is hypothesized to be generated by
      neurokinin-1 receptor (NK1R)-expressing neurons in the preBotzinger complex
      (preBotC), a medullary region proposed to contain the kernel of the circuits
      generating respiration. If this hypothesis is correct, then complete destruction
      of preBotC NK1R neurons should severely perturb and perhaps even fatally arrest
      breathing. Here we show that specific and near complete bilateral (but not
      unilateral) destruction of preBotC NK1R neurons results in both an ataxic
      breathing pattern with markedly altered blood gases and pH, and pathological
      responses to challenges such as hyperoxia, hypoxia and anesthesia. Thus, these
      approximately 600 neurons seem necessary for the generation of normal breathing
      in rats.

PMID- 11528426
TI  - Shape-coding in IT cells generalizes over contrast and mirror reversal, but not
      figure-ground reversal.
AB  - We assessed how the visual shape preferences of neurons in the inferior temporal
      cortex of awake, behaving monkeys generalized across three different stimulus
      transformations. Stimulus-preferences of particular cells among different polygon
      displays were correlated across reversed contrast polarity or mirror reversal,
      but not across figure-ground reversal. This corresponds with psychological
      findings on human shape judgments. Our results imply that neurons in inferior
      temporal cortex respond to components of visual shape derived only after figure
      ground assignment of contours, not to the contours themselves.

PMID- 11528425
TI  - Telencephalic origin of human thalamic GABAergic neurons.
AB  - In non-primate mammalian species, telencephalic and diencephalic neurons
      originate from their respective local proliferative zones. Using vital dye
      labeling in organotypic slice cultures, we show that in human brain, a contingent
      of neurons from the ganglionic eminence of the telencephalon migrate to the
      dorsal thalamic association nuclei of the diencephalon. These neurons rely on
      homotypic-neurophilic guidance during their migration, are GABAergic, and express
      Dlx1/2 homeodomain-containing proteins. Similar experiments in a non-human
      primate and in rodent embryos did not reveal a similar migratory pathway.
      Migration assays demonstrated that the human dorsal thalamus attracts
      telencephalic cells, an effect not observed in the mouse, in which such migration
      is inhibited by chemorepulsive cues. These data suggest that modifications in the
      pattern of migratory guidance cues in the forebrain may underlie the appearance
      of a new migratory pathway and thus contribute to the evolutionary expansion of
      the thalamic association nuclei in the human.

PMID- 11528427
TI  - The role of withdrawal in heroin addiction: enhances reward or promotes
      avoidance?
AB  - The compulsive nature of heroin abuse has been attributed to the fact that drug
      self-administration enables an addict to escape from and avoid the severe
      withdrawal symptoms resulting from opiate dependence. However, studies of
      incentive learning under natural motivational states suggest an alternative
      hypothesis, that withdrawal from heroin functions as a motivational state that
      enhances the incentive value of the drug, thereby enabling it to function as a
      much more effective reward for self-administration. In support of this
      hypothesis, we show here that previous experience with heroin in withdrawal is
      necessary for subsequent heroin-seeking behavior to be enhanced when dependent
      rats once again experience withdrawal.

PMID- 11528428
TI  - Prefrontal [correction of Prefontal] cortex in long-term memory: an
      "interference" approach using magnetic stimulation.
AB  - Neuroimaging has consistently shown engagement of the prefrontal cortex during
      episodic memory tasks, but the functional relevance of this metabolic/hemodynamic
      activation in memory processing is still to be determined. We used repetitive
      transcranial magnetic stimulation (rTMS) to transiently interfere with either
      left or right prefrontal brain activity during the encoding or retrieval of
      pictures showing complex scenes. We found that the right dorsolateral prefrontal
      cortex (DLPFC) was crucial for the retrieval of the encoded pictorial
      information, whereas the left DLPFC was involved in encoding operations. This
      'interference' approach allowed us to establish whether a cortical area activated
      by a memory task actually contributes to behavioral performance.

PMID- 11528431
TI  - Decision time at Yucca Mountain.

PMID- 11528429
TI  - Enhanced visual spatial attention ipsilateral to rTMS-induced 'virtual lesions'
      of human parietal cortex.
AB  - The breakdown of attentional mechanisms after brain damage can have drastic
      behavioral consequences, as in patients suffering from spatial neglect. While
      much research has concentrated on impaired attention to targets contralateral to
      sites of brain damage, here we report the ipsilateral enhancement of visual
      attention after repetitive transcranial magnetic stimulation (rTMS) of parietal
      cortex at parameters known to reduce cortical excitability. Normal healthy
      subjects received rTMS (1 Hz, 10 mins) over right or left parietal cortex.
      Subsequently, detection of visual stimuli contralateral to the stimulated
      hemisphere was consistently impaired when stimuli were also present in the
      opposite hemifield, mirroring the extinction phenomenon commonly observed in
      neglect patients. Additionally, subjects' attention to ipsilateral targets
      improved significantly over normal levels. These results underline the potential
      of focal brain dysfunction to produce behavioral improvement and give
      experimental support to models of interhemispheric competition in the distributed
      brain network for spatial attention.

PMID- 11528432
TI  - Women worse off (cont.).

PMID- 11528433
TI  - Japan's plans for space merger spark fears for basic research.

PMID- 11528434
TI  - Stem-cell list offers sixty-four lines.

PMID- 11528435
TI  - Elusive fossil could conceal answer to dinosaur debate.

PMID- 11528438
TI  - Joint venture on biochips ends in disarray.

PMID- 11528439
TI  - It's a dog's life for Siberian foxes.

PMID- 11528440
TI  - Funding bonanza for astronomy and biotech in Australia.

PMID- 11528443
TI  - Green-fingered gang could hold climate key.

PMID- 11528446
TI  - Out of sight, out of mind?

PMID- 11528444
TI  - Earliest malaria DNA found in Roman baby graveyard.

PMID- 11528447
TI  - Brought down to Earth.

PMID- 11528448
TI  - Collaboration with Japan could be more tempting.

PMID- 11528449
TI  - Could a website teach communication skills?

PMID- 11528450
TI  - Curious effects created by reversal of colour.

PMID- 11528455
TI  - Victor and victim.

PMID- 11528456
TI  - Reasoning for results.

PMID- 11528457
TI  - Achilles' heel of cancer?

PMID- 11528458
TI  - Quantum optics. Photons yield to peer pressure.

PMID- 11528461
TI  - Quantum engineering. Protecting the quantum world.

PMID- 11528460
TI  - Cardiovascular biology. Creating unique blood vessels.

PMID- 11528463
TI  - Chemistry. Mystery of an interstellar ion.

PMID- 11528462
TI  - Immunology. Antibody alterations.

PMID- 11528465
TI  - Mother's voice recognition by seal pups.

PMID- 11528466
TI  - Palaeontology. The beaks of ostrich dinosaurs.
AB  - Primitive ornithomimids, a ubiquitous group of specialized Cretaceous dinosaurs
      nested within a clade of predominantly carnivorous theropods, are known to have
      had teeth, whereas derived ornithomimids had an edentulous beak, which has
      prompted speculation about their dietary habits. Here we describe two new
      ornithomimid specimens in which soft-tissue structures of the beak have been
      preserved. These creatures probably used their beaks to strain food sediment in
      an aqueous environment, rather than for predation on large animals.

PMID- 11528467
TI  - Nanostructures. Self-assembled domain patterns.
AB  - The ordered domain patterns that form spontaneously in a wide variety of chemical
      and physical systems as a result of competing interatomic interactions can be
      used as templates for fabricating nanostructures. Here we describe a new self
      assembling domain pattern on a solid surface that involves two surface structures
      of lead on copper. The evolution of the system agrees with theoretical
      predictions, enabling us to probe the interatomic force parameters that are
      crucial to the process.

PMID- 11528468
TI  - Malaria. Cooperative silencing elements in var genes.
AB  - Each Plasmodium falciparum malaria parasite carries about 50 var genes from a
      diverse family that encode variable adhesion proteins on the infected red blood
      cells of the host, but individual parasites single out just one var gene for
      expression and silence all the others. Here we show that this silencing is
      established during the DNA-synthesis phase (S phase) of the cell cycle and that
      it depends on the cooperative interaction between two elements in separate
      control regions of each var gene (the 5'-flanking region and the intron). This
      finding should help to clarify the mechanisms by which parasites coordinate the
      silencing and activation of var genes that are responsible for antigenic
      variation in malaria.

PMID- 11528470
TI  - Identification of an angiogenic mitogen selective for endocrine gland
      endothelium.
AB  - The known endothelial mitogens stimulate growth of vascular endothelial cells
      without regard to their tissue of origin. Here we report a growth factor that is
      expressed largely in one type of tissue and acts selectively on one type of
      endothelium. This molecule, called endocrine-gland-derived vascular endothelial
      growth factor (EG-VEGF), induced proliferation, migration and fenestration (the
      formation of membrane discontinuities) in capillary endothelial cells derived
      from endocrine glands. However, EG-VEGF had little or no effect on a variety of
      other endothelial and non-endothelial cell types tested. Similar to VEGF, EG-VEGF
      possesses a HIF-1 binding site, and its expression is induced by hypoxia. Both EG
      VEGF and VEGF resulted in extensive angiogenesis and cyst formation when
      delivered in the ovary. However, unlike VEGF, EG-VEGF failed to promote
      angiogenesis in the cornea or skeletal muscle. Expression of human EG-VEGF
      messenger RNA is restricted to the steroidogenic glands, ovary, testis, adrenal
      and placenta and is often complementary to the expression of VEGF, suggesting
      that these molecules function in a coordinated manner. EG-VEGF is an example of a
      class of highly specific mitogens that act to regulate proliferation and
      differentiation of the vascular endothelium in a tissue-specific manner.

PMID- 11528472
TI  - Stimulated emission of polarization-entangled photons.
AB  - Entangled photon pairs-discrete light quanta that exhibit non-classical
      correlations-play a crucial role in quantum information science (for example, in
      demonstrations of quantum non-locality, quantum teleportation and quantum
      cryptography). At the macroscopic optical-field level non-classical correlations
      can also be important, as in the case of squeezed light, entangled light beams
      and teleportation of continuous quantum variables. Here we use stimulated
      parametric down-conversion to study entangled states of light that bridge the gap
      between discrete and macroscopic optical quantum correlations. We demonstrate
      experimentally the onset of laser-like action for entangled photons, through the
      creation and amplification of the spin-1/2 and spin-1 singlet states consisting
      of two and four photons, respectively. This entanglement structure holds great
      promise in quantum information science where there is a strong demand for
      entangled states of increasing complexity.

PMID- 11528471
TI  - Characterization of extrasolar terrestrial planets from diurnal photometric
      variability.
AB  - The detection of massive planets orbiting nearby stars has become almost routine,
      but current techniques are as yet unable to detect terrestrial planets with
      masses comparable to the Earth's. Future space-based observatories to detect
      Earth-like planets are being planned. Terrestrial planets orbiting in the
      habitable zones of stars-where planetary surface conditions are compatible with
      the presence of liquid water-are of enormous interest because they might have
      global environments similar to Earth's and even harbour life. The light scattered
      by such a planet will vary in intensity and colour as the planet rotates; the
      resulting light curve will contain information about the planet's surface and
      atmospheric properties. Here we report a model that predicts features that should
      be discernible in the light curve obtained by low-precision photometry. For
      extrasolar planets similar to Earth, we expect daily flux variations of up to
      hundreds of per cent, depending sensitively on ice and cloud cover as well as
      seasonal variations. This suggests that the meteorological variability,
      composition of the surface (for example, ocean versus land fraction) and rotation
      period of an Earth-like planet could be derived from photometric observations.
      Even signatures of Earth-like plant life could be constrained or possibly, with
      further study, even uniquely determined.

PMID- 11528473
TI  - Mechanism for the destruction of H+3 ions by electron impact.
AB  - The rate at which the simplest triatomic ion (H+3) dissociates following
      recombination with a low-energy electron has been measured in numerous
      experiments. This process is particularly important for understanding
      observations of H+3 in diffuse interstellar clouds. But, despite extensive
      efforts, no theoretical treatment has yet proved capable of predicting the
      measured dissociative recombination rates at low energy, even to within an order
      of magnitude. Here we show that the Jahn-Teller symmetry-distortion effect-almost
      universally neglected in the theoretical description of electron-molecule
      collisions-generates recombination at a much faster rate than any other known
      mechanism. Our estimated rate constant overlaps the range of values spanned by
      experiments. We treat the low-energy collision process as a curve-crossing
      problem, which was previously thought inapplicable to low-energy recombination in
      H+3. Our calculation reproduces the measured propensity for three-body versus two
      body breakup of the neutral fragments, as well as the vibrational distribution of
      the H2 product molecules.

PMID- 11528474
TI  - Parasitic computing.
AB  - Reliable communication on the Internet is guaranteed by a standard set of
      protocols, used by all computers. Here we show that these protocols can be
      exploited to compute with the communication infrastructure, transforming the
      Internet into a distributed computer in which servers unwittingly perform
      computation on behalf of a remote node. In this model, which we call 'parasitic
      computing', one machine forces target computers to solve a piece of a complex
      computational problem merely by engaging them in standard communication.
      Consequently, the target computers are unaware that they have performed
      computation for the benefit of a commanding node. As experimental evidence of the
      principle of parasitic computing, we harness the power of several web servers
      across the globe, which-unknown to them-work together to solve an NP complete
      problem.

PMID- 11528475
TI  - Universal behaviour in compressive failure of brittle materials.
AB  - Brittle failure limits the compressive strength of rock and ice when rapidly
      loaded under low to moderate confinement. Higher confinement or slower loading
      results in ductile failure once the brittle-ductile transition is crossed.
      Brittle failure begins when primary cracks initiate and slide, creating wing
      cracks at their tips. Under little to no confinement, wing cracks extend and link
      together, splitting the material into slender columns which then fail. Under low
      to moderate confinement, wing crack growth is restricted and terminal failure is
      controlled by the localization of damage along a narrow band. Early
      investigations proposed that localization results from either the linkage of wing
      cracks or the buckling of microcolumns created between adjacent wing cracks.
      Observations of compressive failure in ice suggest a mechanism whereby
      localization initiates owing to the bending-induced failure of slender
      microcolumns created between sets of secondary cracks emanating from one side of
      a primary crack. Here we analyse this mechanism, and show that it leads to a
      closed-form, quantitative model that depends only on independently measurable
      mechanical parameters. Our model predictions for both the brittle compressive
      strength and the brittle-ductile transition are consistent with data from a
      variety of crystalline materials, offering quantitative evidence for universal
      processes in brittle failure and for the broad applicability of the model.

PMID- 11528476
TI  - Transition of Mount Etna lavas from a mantle-plume to an island-arc magmatic
      source.
AB  - Mount Etna lies near the boundary between two regions that exhibit significantly
      different types of volcanism. To the north, volcanism in the Aeolian island arc
      is thought to be related to subduction of the Ionian lithosphere. On Sicily
      itself, however, no chemical or seismological evidence of subduction-related
      volcanism exists, and so it is thought that the volcanism-including that on Mount
      Etna itself-stems from the upwelling of mantle material, associated with various
      surface tectonic processes. But the paucity of geological evidence regarding the
      primary composition of magma from Mount Etna means that its source
      characteristics remain controversial. Here we characterize the trace-element
      composition of a series of lavas emitted by Mount Etna over the past 500 kyr and
      preserved as melt inclusions inside olivine phenocrysts. We show that the
      compositional change in primary magmas from Mount Etna reflects a progressive
      transition from a predominantly mantle-plume source to one with a greater
      contribution from island-arc (subduction-related) basalts. We suggest that this
      is associated with southward migration of the Ionian slab, which is becoming
      juxtaposed with a mantle plume beneath Sicily. This implies that the volcanism of
      Mount Etna has become more calc-alkaline, and hence more explosive, during its
      evolution.

PMID- 11528477
TI  - Genetic linkage of ecological specialization and reproductive isolation in pea
      aphids.
AB  - The evolution of ecological specialization generates biological diversity and may
      lead to speciation. Genetic architecture can either speed or retard this process.
      If resource use and mate choice have a common genetic basis through pleiotropy or
      close linkage, the resulting genetic correlations can promote the joint evolution
      of specialization and reproductive isolation, facilitating speciation. Here we
      present a model of the role of genetic correlations in specialization and
      speciation, and test it by analysing the genetic architecture of key traits in
      two highly specialized host races of the pea aphid (Acyrthosiphon pisum pisum;
      Hemiptera : Aphididae). We found several complexes of pleiotropic or closely
      linked quantitative trait loci (QTL) that affect key traits in ways that would
      promote speciation: QTL with antagonistic effects on performance on the two hosts
      are linked to QTL that produce asortative mating (through habitat choice). This
      type of genetic architecture may be common in taxa that have speciated under
      divergent natural selection.

PMID- 11528478
TI  - Dynamics of travelling waves in visual perception.
AB  - Nonlinear wave propagation is ubiquitous in nature, appearing in chemical
      reaction kinetics, cardiac tissue dynamics, cortical spreading depression and
      slow wave sleep. The application of dynamical modelling has provided valuable
      insights into the mechanisms underlying such nonlinear wave phenomena in several
      domains. Wave propagation can also be perceived as sweeping waves of visibility
      that occur when the two eyes view radically different stimuli. Termed binocular
      rivalry, these fluctuating states of perceptual dominance and suppression are
      thought to provide a window into the neural dynamics that underlie conscious
      visual awareness. Here we introduce a technique to measure the speed of rivalry
      dominance waves propagating around a large, essentially one-dimensional annulus.
      When mapped onto visual cortex, propagation speed is independent of eccentricity.
      Propagation speed doubles when waves travel along continuous contours, thus
      demonstrating effects of collinear facilitation. A neural model with reciprocal
      inhibition between two layers of units provides a quantitative explanation of
      dominance wave propagation in terms of disinhibition. Dominance waves provide a
      new tool for investigating fundamental cortical dynamics.

PMID- 11528479
TI  - Two-step process for photoreceptor formation in Drosophila.
AB  - The formation of photoreceptor cells (PRCs) in Drosophila serves as a paradigm
      for understanding neuronal determination and differentiation. During larval
      stages, a precise series of sequential inductive processes leads to the
      recruitment of eight distinct PRCs (R1-R8). But, final photoreceptor
      differentiation, including rhabdomere morphogenesis and opsin expression, is
      completed four days later, during pupal development. It is thought that
      photoreceptor cell fate is irreversibly established during larval development,
      when each photoreceptor expresses a particular set of transcriptional regulators
      and sends its projection to different layers of the optic lobes. Here, we show
      that the spalt (sal) gene complex encodes two transcription factors that are
      required late in pupation for photoreceptor differentiation. In the absence of
      the sal complex, rhabdomere morphology and expression of opsin genes in the inner
      PRCs R7 and R8 are changed to become identical to those of outer R1-R6 PRCs.
      However, these cells maintain their normal projections to the medulla part of the
      optic lobe, and not to the lamina where outer PRCs project. These data indicate
      that photoreceptor differentiation occurs as a two-step process. First, during
      larval development, the photoreceptor neurons become committed and send their
      axonal projections to their targets in the brain. Second, terminal
      differentiation is executed during pupal development and the photoreceptors adopt
      their final cellular properties.

PMID- 11528480
TI  - Virus-mediated killing of cells that lack p53 activity.
AB  - A major goal of molecular oncology is to identify means to kill cells lacking p53
      function. Most current cancer therapy is based on damaging cellular DNA by
      irradiation or chemicals. Recent reports support the notion that, in the event of
      DNA damage, the p53 tumour-suppressor protein is able to prevent cell death by
      sustaining an arrest of the cell cycle at the G2 phase. We report here that adeno
      associated virus (AAV) selectively induces apoptosis in cells that lack active
      p53. Cells with intact p53 activity are not killed but undergo arrest in the G2
      phase of the cell cycle. This arrest is characterized by an increase in p53
      activity and p21 levels and by the targeted destruction of CDC25C. Neither cell
      killing nor arrest depends upon AAV-encoded proteins. Rather, AAV DNA, which is
      single-stranded with hairpin structures at both ends, elicits in cells a DNA
      damage response that, in the absence of active p53, leads to cell death. AAV
      inhibits tumour growth in mice. Thus viruses can be used to deliver DNA of
      unusual structure into cells to trigger a DNA damage response without damaging
      cellular DNA and to selectively eliminate those cells lacking p53 activity.

PMID- 11528481
TI  - Rotational movement during cyclic nucleotide-gated channel opening.
AB  - Cyclic nucleotide-gated (CNG) channels are crucial components of visual,
      olfactory and gustatory signalling pathways. They open in response to direct
      binding of intracellular cyclic nucleotides and thus contribute to cellular
      control of both the membrane potential and intracellular Ca2+ levels. Cytosolic
      Ni2+ potentiates the rod channel (CNG1) response to cyclic nucleotides and
      inhibits the olfactory channel (CNG2) response. Modulation is due to coordination
      of Ni2+ by channel-specific histidines in the C-linker, between the S6
      transmembrane segment and the cyclic nucleotide-binding domain. Here we report,
      using a histidine scan of the initial C-linker of the CNG1 channel, stripes of
      sites producing Ni2+ potentiation or Ni2+ inhibition, separated by 50 degrees on
      an alpha-helix. These results suggest a model for channel gating where rotation
      of the post-S6 region around the channel's central axis realigns the Ni2+
      coordinating residues of multiple subunits. This rotation probably initiates
      movement of the S6 and pore opening.

PMID- 11528482
TI  - Ablation of XRCC2/3 transforms immunoglobulin V gene conversion into somatic
      hypermutation.
AB  - After gene rearrangement, immunoglobulin V genes are further diversified by
      either somatic hypermutation or gene conversion. Hypermutation (in man and mouse)
      occurs by the fixation of individual, non-templated nucleotide substitutions.
      Gene conversion (in chicken) is templated by a set of upstream V pseudogenes.
      Here we show that if the RAD51 paralogues XRCC2, XRCC3 or RAD51B are ablated the
      pattern of diversification of the immunoglobulin V gene in the chicken DT40 B
      cell lymphoma line exhibits a marked shift from one of gene conversion to one of
      somatic hypermutation. Non-templated, single-nucleotide substitutions are
      incorporated at high frequency specifically into the V domain, largely at G/C and
      with a marked hotspot preference. These mutant DT40 cell lines provide a
      tractable model for the genetic dissection of immunoglobulin hypermutation and
      the results support the idea that gene conversion and somatic hypermutation
      constitute distinct pathways for processing a common lesion in the immunoglobulin
      V gene. The marked induction of somatic hypermutation that is achieved by
      ablating the RAD51 paralogues is probably a consequence of modifying the
      recombination-mediated repair of such initiating lesions.

PMID- 11528485
TI  - Adverse profile of dietary nutrients, anthropometry and lipids in urban slum
      dwellers of northern India.
AB  - OBJECTIVES: The intra-country rural to urban migrant populations undergo radical
      socio-economic and lifestyle changes in a developing country. Therefore, it is an
      interesting sample in which to study nutrition pattern, anthropometry and
      metabolic profile. The aim of this study was to assess nutrient profile and its
      association with the anthropometry, percentage body fat (%BF) and blood lipids in
      the urban slum dwellers in northern India. DESIGN: A cross sectional
      epidemiological descriptive study. SETTINGS: The study was conducted in urban
      slum colony of Gautam Nagar, situated in a southern area of New Delhi. SUBJECTS:
      The data was recorded in 227 subjects (52 males and 175 females). RESULTS: The
      diets averaged approximately 59-60% of energy from carbohydrates, 12-13% energy
      from protein, and 24-27% energy from dietary total fat. Lower intake of
      monounsaturated fatty acids (MUFA), a low ratio of n-6/n-3 fatty acids, a high
      ratio of polyunsaturated and saturated fatty acids, a high intake of erucic acid,
      and a low consumption of fibre and vitamin E intake were significant
      observations. Although their mean body mass index (BMI) was in a low range
      (20.5+/-4.2), %BF was high in females (26.7+/-8.6%; P=0.001), and a high
      prevalence of abdominal obesity was observed in both males (22%) and females
      (16%). Moreover, there was high prevalence of hypercholesterolemia,
      hypertriglyceridemia and, in particular, low levels of high-density lipoprotein
      cholesterol. Those consuming a high-fat diet (>30%) also consumed high MUFA, n-3
      fatty acids, saturated fat and dietary cholesterol. Carbohydrate intake as
      percentage energy was a significant predictor of the levels of triacylglycerol in
      males, while in females significant predictors for triacylglycerol include intake
      of carbohydrate as percentage energy, age, %BF and BMI. CONCLUSION: In this
      economically deprived population, now constituting approximately 30-50% of the
      urban population of major cities in India, such adverse dietary, anthropometric
      and metabolic factors are predictors of early and accelerated atherosclerosis.
      SPONSORSHIP: This study was fully supported by a financial grant from the Science
      and Society Division, Department of Science and Technology, Ministry of Science
      and Technology, Government of India.

PMID- 11528486
TI  - Relative validity of a semi-quantitative food frequency questionnaire versus 28
      day weighed diet records in Japanese female dietitians.
AB  - OBJECTIVE: To assess the relative validity of a semi-quantitative food frequency
      questionnaire (SQFFQ) against 28 day weighed diet records (WDRs). SUBJECTS AND
      METHODS: The SQFFQ was administered to 106 (21 male and 85 female) Japanese
      dietitians in Aichi Prefecture in autumn, 1996 and four-season consecutive 7 day
      WDRs were carried out during 1996-1997. We evaluated validity of intakes of 15
      foods and 31 macro- and micro-nutrients based on the SQFFQ against those
      according to 28 day WDRs among 79 Japanese female dietitians. RESULTS: Mean daily
      intakes of selected foods and nutrients determined by the SQFFQ were generally
      equivalent to those measured by 28 day WDRs. Pearson's de-attenuated correlation
      coefficients (CCs) with log-transformation and energy-adjustment between intakes
      of selected foods and nutrients quantified by the SQFFQ and 28 day WDRs (minimum
      median-maximum) ranged from 0.17 (beverages)-0.52 to 0.74 (rice), and Spearman's
      rank CCs with energy-adjustment ranged from 0.28 (confectionery)-0.42 to 0.68
      (rice). Respective Pearson's CCs for intakes of nutrients were 0.28 (PUFAs)-0.51
      to 0.73 (magnesium), and Spearman's rank CCs ranged from 0.23 (n-3 PUFAs)-0.45 to
      0.71 (magnesium). Favorably higher agreement for intakes of foods/nutrients was
      achieved along with lower disagreement. CONCLUSIONS: Satisfactorily higher
      relative validity was attained in Japanese female dietitians with the SQFFQ. This
      calibrated questionnaire seems therefore appropriate for administration to
      Japanese dietitians to clarify associations between diet and health/disease.
      SPONSORSHIP: A grant-in-aid from the Ministry of Education, Science, Sports and
      Culture (06454242).

PMID- 11528487
TI  - Assessment of nutritional folate status and selected vitamin status of women of
      childbearing age.
AB  - OBJECTIVE: The aim of the study was to investigate folate and other selected
      vitamin status (ascorbic acid, tocopherol, retinol, vitamin B12), haematological
      indices and total homocysteine concentration of serum in women of childbearing
      age. DESIGN: A cross-sectional study. SETTING: Warsaw. SUBJECTS: Healthy women
      aged 18-30 y (n=78) not pregnant presently or previously, and not taking drugs.
      RESULTS: Haemoglobin and haematocrit values according to WHO criteria for 18 to
      30-y-old women were normal. The optimal levels of serum tocopherol, >1.29 mg/dl
      (>29.9 micromol/l) to preventing civilization diseases, were found in 5.5% and
      serum retinol >71.6 mcg/dl (>2.5 micromol/l) in 6.4% of all studied persons. The
      analysis of serum folate concentration showed high-risk deficiency,<3 ng/ml (<6.8
      nmol/l), in 6.4%, moderate and low risk together (7.0-14.9 nmol/l) in 61.6% and
      optimal folate levels (>14.9 nmol/l) in 32.0% of the studied group. Folate body
      stores were insufficient in almost all women. There was no high or moderate
      deficiency risk of vitamin B12 or ascorbic acid. None of the women under study
      had serum total homocysteine (tHcy) concentration >15 micromol/l, indicating
      hyperhomocysteinaemia. Serum total homocysteine concentrations in the range of 5
      15 micromol/l were found in 71.8%, and serum tHcy >10 micromol/l in 7.7% of the
      studied group of women. SPONSORSHIP: The study was sponsored by the Polish
      Committee for Scientific Research.

PMID- 11528488
TI  - Effects of palm oil and dietary cholesterol on plasma lipoproteins: results from
      a dietary crossover trial in free-living subjects.
AB  - OBJECTIVE: To study the effects of palm oil (PO) and egg consumption (E) on
      plasma lipoproteins. DESIGN: Randomized crossover trial. SETTING: Free-living
      subjects. SUBJECTS: Twenty-eight healthy male students aged 20-34 y.
      INTERVENTIONS: Four typical Colombian diets (10 878 kJ/day; 57% energy in
      carbohydrates, 12% energy in proteins and 31% energy in fats) were consumed for 4
      weeks. The HPOLC diet was high in PO (8.8% energy as palmitic acid, PA) and low
      in eggs (181.2 mg/kJ of dietary cholesterol, DC); the HPOHC diet was high in PO
      and high in eggs (866.1 mg/kJ of DC); the MPOMC diet was moderate in PO (6.3%
      energy as PA) and moderate in eggs (581.6 mg/kJ of DC); and the LOPOMC diet had
      no PO and was moderate in eggs (543.9 mg/kJ of DC). MAIN OUTCOME: Total (TC), low
      density (LDL-c), and high density lipoprotein cholesterol (HDL-c), and
      triacylglycerols (TAG) were measured on a pool of three fasting blood samples
      collected in consecutive days the last week of each diet. RESULTS: Comparison of
      the HPOHC and HPOLC diets showed increases in TC and LDL-c of 0.21 (P=0.01), and
      0.16 mmol/l (P=0.05). Comparison of LOPOMC and MPOMC diets showed increases in TC
      and LDL-c of 0.39 (P<0.001), and 0.38 mmol/l (P<0.001), respectively. No
      significant changes in HDL-c or TAG were observed. CONCLUSIONS: Our findings
      suggest that non-extreme short-term changes in PO and DC consumption lead to
      significant elevations in plasma TC and LDL-c. SPONSORSHIP: CENIPALMA, Fundacion
      Cardiovascular del Oriente Colombiano, Universidad Industrial de Santander.

PMID- 11528489
TI  - Fatty acid absorption in preterms on formulas with and without long-chain
      polyunsaturated fatty acids and in terms on formulas without these added.
AB  - BACKGROUND/OBJECTIVE: Long chain polyunsaturated fatty acids have beneficial
      effects in preterm neurophysiological development and are semi-essential. Their
      levels and variation in plasma and red cells in term and preterms are better
      known than their intestinal absorption. In this paper the absorption of
      supplemented arachidonic acid (AA) and docosahexaenoic acid (DHA) is evaluated in
      a preterm group. DESIGN: Four newborn randomized groups were studied. Group T
      comprised 11 terms on regular formula. Preterms: group P (n=9) was on a classic
      preterm formula. INTERVENTION: groups PA (n=9) and PB (n=13) were on the same
      formula but PB contained AA and DHA in similar proportion to breast milk. At 20
      days a 3 day metabolic balance was taken for Ca, P(i), Mg, total fat and
      individual fatty acids (C8-C24, saturated unsaturated). RESULTS: Calcium
      absorption was (mean+/-s.d.) 51+/-13% in terms. In preterms it was respectively
      45+/-18, 38+/-11 and 37+/-21%. Total fat absorption was 92.0+/-8.0% in terms, and
      from 95.0+/-2.0 to 91.0+/-8.0% in preterms. Absorption of 8:0, 10:0 and 12:0
      showed a very high and constant rate despite significant intake differences (715
      33 mg/kg/day). Linoleic acid and alpha-linolenic acid were absorbed in the three
      groups at around 94% regardless of a greater LA intake in group P. Details of
      absorption (mg/kg/day) were: for AA, intake 17+/-7, fecal excretion 5+/-4, net
      retention 12+/-5 (75.0+/-18%); for DHA, intake 10+/-3, fecal excretion 3+/-2, net
      retention 6+/-4 (62.3+/-30%). CONCLUSION: Intestinal absorption of fatty acids is
      high and is comparable in terms and preterms as regards the studied acids. Longer
      acids were less well absorbed. The supplemented amounts of AA and DHA were less
      well absorbed and probably not impairing calcium absorption. SPONSORSHIP:
      University of Alicante, University of Miguel Hernandez.

PMID- 11528490
TI  - Mild iodine deficiency is associated with elevated hearing thresholds in children
      in Benin.
AB  - OBJECTIVE: Elevated hearing thresholds have been demonstrated in populations
      afflicted by endemic cretinism as a result of severe iodine deficiency. However,
      data on the effects of less severe iodine deficiency on hearing thresholds in
      apparently normal children are scant. This study addresses the question whether
      there is a relationship among iodine variables, hearing and mental performance in
      a mildly iodine-deficient population. DESIGN: A randomized, placebo-controlled
      intervention trial with an observation period of 11 months. SETTING: An iodine
      deficient area in northern Benin. SUBJECTS: A total of 197 school children, aged
      7-11 y. INTERVENTIONS: A total of 97 children received an oral dose of iodized
      oil, containing 540 mg I, while 100 children received a placebo. About 3-4 months
      after supplementation, the whole population began to have access to iodized salt.
      Non-verbal mental tests were administered and biochemical indicators
      (thyrotropin, free thyroxine, thyroglobulin and urinary iodine) were measured at
      the beginning and the end of the study. Hearing was measured at the end of the
      study in both ears by pure-tone audiometry at seven frequencies. RESULTS: In this
      mildly iodine-deficient child population children with higher serum thyroglobulin
      concentrations had significantly higher hearing thresholds in the higher
      frequency range (> or = 2000 Hz) than children with lower serum thyroglobulin
      concentration. Moreover children with lower hearing thresholds performed
      significantly better on the mental tests used. CONCLUSIONS: Even when iodine
      deficiency is 'mild', promotion of adequate iodine intake through salt iodization
      programs and other means remains crucial. SPONSORSHIP: Nestle Foundation,
      Lausanne, Switzerland; Wageningen University, Wageningen, The Netherlands.

PMID- 11528492
TI  - Soy product intake and premenopausal hysterectomy in a follow-up study of
      Japanese women.
AB  - OBJECTIVE: The estrogenicity of dietary soy may increase the risk of diseases,
      such as uterine leiomyoma and endometriosis, which originate from uterine tissue
      and are predominant indications for hysterectomy. We sought to determine whether
      soy product intake is associated with an increased risk of premenopausal
      hysterectomy. DESIGN: Prospective cohort study. SETTING: Takayama City, Gifu,
      Japan. SUBJECTS: A cohort of 1172 female residents randomly selected from
      participants in the Takayama Study who were aged 35-54 and premenopausal at the
      time they entered the study in 1992. MEASUREMENTS: Diet including soy product and
      isoflavone intake was assessed by a validated semiquantitative food frequency
      questionnaire at baseline. Information on the onset of menopause and hysterectomy
      were obtained by a follow-up mail questionnaire in 1998. RESULTS: During the 6 y
      study period, 31 women underwent premenopausal hysterectomies. The second tertile
      of isoflavone intake was significantly associated with an decreased risk of
      premenopausal hysterectomy compared to the lowest tertile of intake after
      controlling for age and total energy (rate ratio=0.35, 95% confidence interval
      0.13-0.97), although the dose-response relationship was not statistically
      significant. CONCLUSIONS: It is possible that soy product intake may be inversely
      associated with diagnoses leading to hysterectomy. Future studies focusing on
      specific diseases will be required to examine this possibility. SPONSORSHIP:
      Grants from the Ministry of Education, Science, Sports and Culture, Japan.

PMID- 11528491
TI  - Comparison of gastric emptying of a solid and a liquid nutritional rehabilitation
      food.
AB  - OBJECTIVE: To compare gastric emptying of a solid and a liquid nutritional
      rehabilitation food. DESIGN: Cross-over trial. Eight volunteers took, in random
      order at least 1 week apart, 2100 kJ of a solid and a liquid nutritional
      rehabilitation food with added labelled [13C] glycine. SETTING: Research ward for
      healthy volunteers. SUBJECTS: Eight healthy volunteers. METHODS: Appearance of
      13CO2 was monitored in expired gas every 15 min for 240 min after meal intake and
      compared between solid and liquid meals. Parameters of gastric emptying were then
      calculated. RESULTS: Gastric half-emptying time was slightly longer for solid
      meal compared to liquid meal (101+/-6.0 vs 88+/-9.8 min, P=0.24). 13CO2 excretion
      peaked 138+/-5.3 min after the solid meal compared with 119+/-8.6 min with liquid
      meal (P=0.06). 13CO2 excretion was higher for the liquid food up to 110 min after
      the meal but then became higher for the solid food. Analysis of variance for
      repeated measures of 13CO2 excretion showed a significant interaction term
      between the type of food and time indicating a delayed elimination of 13CO2 for
      the solid food (P=0.018). CONCLUSIONS: Attempts to replace liquid nutritional
      rehabilitation foods by a solid food in malnourished patients should take into
      account a possible slower gastric emptying. SPONSORSHIP: Supported by a grant
      from Nutriset (Malaunay, France) and ANVAR (Agence Nationale de la Valorisation
      de la Recherche, contract no. A9703021P).

PMID- 11528493
TI  - High bioavailability of calcium in fortified Horlicks.
AB  - OBJECTIVE: To compare the bioavailability of calcium carbonate-fortified Horlicks
      with calcium naturally present in milk. DESIGN: Randomised crossover within
      subject comparison using a double label stable isotope technique. SETTING:
      Institute of Food Research, Human Nutrition Unit. PARTICIPANTS: Sixteen pre
      menopausal women aged 23-40 y, habituated to a high-calcium diet (mean 1240
      mg/day). RESULTS: Mean true fractional calcium absorption was 38.8% (s.d.+/-14.5)
      from Horlicks and 21.2% (s.d.+/-4.6) from milk. Significantly more calcium was
      absorbed from a serving of Horlicks than from the same quantity of calcium
      present in 420 g semi-skimmed milk (P<0.001). CONCLUSIONS: Fortified Horlicks is
      a highly bioavailable source of calcium. A single serving, containing at least
      500 mg calcium, provides half the reference nutrient intake for the population
      sub-group with the highest requirement (adolescent boys) and more than half for
      all others. SPONSORSHIP: SmithKline Beecham funded this research project.

PMID- 11528494
TI  - Obesity and body mass index in Spain: the 'single population' theory revisited.
AB  - OBJECTIVE: The 'single population' theory suggests that the distribution of body
      mass index (BMI) moves up and down as a whole. We test directly whether this
      theory is valid among the adult population within one country over time, by
      examining the association between median BMI and the prevalence of obesity in the
      adult population of Spain's 17 regions between 1987 and 1993. DESIGN AND SETTING:
      Ecological study using data from two national health surveys. SUBJECTS AND
      INTERVENTIONS: Self-reported weight and height for persons aged 20-64 y were
      drawn from representative Spanish-population samples from two similar National
      Health Surveys carried out in 1987 (n = 20 705) and 1993 (n = 15 490). MAIN
      OUTCOME MEASURES: Correlation and linear regression between the difference in
      median BMI and the difference in the prevalence of obesity (BMI > or = 30
      kg/m(2)) between 1987 and 1993. RESULTS: Between 1987 and 1993 the change in
      median BMI was in general strongly correlated with the change in the prevalence
      of obesity (r = 0.85; P < 0.001). The correlation is greater in women, persons
      over 45 y, and those with lower educational levels. Between 1987 and 1993 each
      unit of increase in median BMI is associated with an absolute increase of 5.1%
      (95% CI 3.3-6.8%) in the prevalence of obesity. CONCLUSIONS: The single
      population hypothesis holds true among the adult population within a whole
      country over time. This could be useful for monitoring and understanding the
      prevalence of obesity within a population.

PMID- 11528495
TI  - Plasma antioxidant capacity of HIV-seropositive and healthy subjects during long
      term ingestion of fruit juices or a fruit-vegetable-concentrate containing
      antioxidant polyphenols.
AB  - OBJECTIVE: To investigate whether antioxidant polyphenols from fruit juices or a
      fruit-vegetable-concentrate increase the plasma antioxidant capacity in HIV
      infected and healthy subjects. DESIGN: Twenty-three HIV-seropositive and 18
      seronegative adults were randomized to ingest either 1 l of fruit juice or 30 ml
      fruit-vegetable-concentrate per day over 16 weeks in addition to their normal
      Western diet. METHODS: Plasma antioxidant capacity was determined as Trolox
      equivalent antioxidant capacity (TEAC) at baseline, after 1 and 16 weeks of
      intervention, and after a 6 week washout. RESULTS: There was no difference in
      plasma antioxidant capacity between HIV-infected and healthy subjects at baseline
      (P=0.1). After 16 weeks of intervention TEAC increased in HIV-positive subjects
      with both types of polyphenol supplementation (juice, 1.38+/-0.07 to 1.42+/-0.04
      mM, P=0.034; concentrate, 1.40+/-0.09 to 1.46+/-0.08 mM, P=0.025). TEAC was not
      altered by either type of supplementation in HIV-seronegative subjects.
      CONCLUSION: Plasma antioxidant capacity can be increased by long-term ingestion
      of polyphenols from fruit juices or fruit-vegetable-concentrate in HIV
      seropositive but not in HIV-seronegative subjects. SPONSORSHIP: This study was
      supported by a grant and Cellagon aurum from HG Berner GmbH, Altenholz, and fruit
      juices from Eckes Granini GmbH & Co. KG, Nieder-Olm.

PMID- 11528497
TI  - An association between chronic undernutrition and educational test scores in
      Vietnamese children.
AB  - OBJECTIVE: To examine the association between results of educational tests and
      the anthropometric status of schoolchildren. DESIGN: Cross-sectional data
      collected during the baseline survey of a randomised trial. SETTING: Eighty-one
      primary schools in three districts of northern Vietnam. SUBJECTS: A total of 3055
      schoolchildren enrolled in class 3 and born in 1990. MAIN OUTCOME MEASURES: Tests
      of mathematics and Vietnamese language developed not to show floor or ceiling
      effects, and Z-scores of height-for-age, weight-for-age and weight-for-height.
      RESULTS: After controlling for age, sex, district and school the results of test
      scores in both mathematics and Vietnamese were significantly negatively
      correlated with Z-scores of height-for-age (P<0.001) and weight-for-age
      (P<0.001), but not with weight-for-height (P=0.75). CONCLUSIONS: A cross
      sectional negative association was observed in Vietnamese primary school children
      between indicators of chronic undernutrition and tests of educational
      achievement. SPONSORSHIP: The study was funded by donors to the Partnership for
      Child Development including the Rockefeller Foundation and the World Bank.

PMID- 11528496
TI  - Folate fortification: potential impact on folate intake in an older population.
AB  - OBJECTIVE: To examine the potential impact of different models of folate
      fortification of Australian foods on the folate intakes of older Australians.
      DESIGN: Dietary data were collected using a food frequency questionnaire from
      people attending a population-based health study. SETTING: Two postcode areas
      west of Sydney, Australia. SUBJECTS: A total of 2895 people aged over 49 y,
      obtained from a door knock census (79% of 3654 subjects examined). MAIN OUTCOME
      MEASURES: The folate intake in this population was estimated using four different
      models: (1) pre-fortification folate values; (2) current voluntary folate
      fortification in Australia; (3) universal fortification of all foods permitted to
      add folate, at 25% recommended dietary intake (RDI) per reference serve; and (4)
      universal fortification of all foods permitted to add folate, at 50% RDI per
      reference serve. The increased bioavailability of synthetic folic acid (SFA) was
      included in the analysis. RESULTS: At current voluntary folate fortification,
      approximately 65% of this population consume 320 microg dietary folate
      equivalents (DFE) or more per day from diet and supplements, and 0.4% (n=10)
      consume greater than the recommended upper safety level of 1000 microg from SFA.
      More than 95% of this older population would be expected to consume more than 320
      microg DFE from diet and supplements with universal fortification at 50% of the
      RDI, and 0.5% (n=14) may consume greater than 1000 microg/day of SFA.
      CONCLUSIONS: There is unlikely to be a large increase in the proportion of older
      persons who are likely to consume more than the upper safety level of intake with
      universal folate fortification. As most of those who currently or are predicted
      to consume over 1000 microg SFA take supplements containing folic acid, it is
      highly recommended that vitamin B12 be included in any vitamin supplements
      containing folate. SPONSORSHIP: This study was supported by the Australian
      National Health and Medical Research Council (NHMRC).

PMID- 11528498
TI  - Obesity and associated factors in a Palestinian West Bank village population.
AB  - OBJECTIVE: To describe body mass index (BMI), waist circumference and waist-hip
      ratio in a Palestinian West Bank village population, and to assess the
      associations of these variables to blood pressure and serum lipids. DESIGN: Cross
      sectional study. SETTING: Community-based study in a prototypic semi-rural
      Palestinian village in the central West Bank. SUBJECTS: All individuals aged 30
      65 y in the study village were invited for the study and 500 (85%) participated.
      MAIN OUTCOME MEASURES: BMI > or = 30 was used as the measure of obesity. RESULTS:
      The prevalence of obesity was 37.5% among women and 18.8% among men. The
      prevalence of abdominal obesity was 62.5% among women and 14.8% among men. BMI
      seemed to be the more important correlate of blood pressure whereas waist-hip
      ratio seemed to be the more important correlate of serum triglycerides, compared
      to the other obesity measures. CONCLUSIONS: The prevalence of obesity in the
      study population was very high compared to most other countries in the world,
      particularly among women. SPONSORSHIP: The study was funded by the Norwegian
      Universities' Committee for Development Research (NUFU). LCM Stene was supported
      by a grant from the Throne Holst Foundation.

PMID- 11528500
TI  - Complete exon-intron structure of the RPGR-interacting protein (RPGRIP1) gene
      allows the identification of mutations underlying Leber congenital amaurosis.
AB  - Leber congenital amaurosis (LCA) is a genetically heterogeneous autosomal
      recessive condition responsible for congenital blindness or greatly impaired
      vision since birth. So far, six LCA loci have been mapped but only 4 out of 6
      genes have been identified. A genome-wide screen for homozygosity was conducted
      in seven consanguineous families unlinked to any of the six LCA loci. Evidence
      for homozygosity was found in two of these seven families at the 14q11
      chromosomal region. Two retinal specific candidate genes were known to map to
      this region, namely the neural retina leucine zipper (NRL) and the retinitis
      pigmentosa GTPase regulator interacting protein (RPGRIP1). No mutation of the NRL
      gene was found in any of the two families. Thus, we determined the complete exon
      intron structure of the RPGRIP1 gene. RPGRIP1 encompasses 24 coding exons, nine
      of which are first described here with their corresponding exon-intron
      boundaries. The screening of the gene in the two families consistent with linkage
      to chromosome 14q11 allowed the identification of a homozygous null mutation and
      a homozygous missense mutation, respectively. Further screening of LCA patients
      unlinked to any of the four already identified LCA genes (n=86) identified seven
      additional mutations in six of them. In total, eight distinct mutations (5 out of
      8 truncating) in 8/93 patients were found. So far this gene accounts for eight
      out of 142 LCA cases in our series (5.6%).

PMID- 11528501
TI  - Partial tetrasomy 12pter-12p12.3 in a girl with Pallister-Killian syndrome:
      extraordinary finding of an analphoid, inverted duplicated marker.
AB  - Cytogenetic analysis in a girl with multiple congenital anomalies indicating
      Pallister-Killian syndrome (PKS) showed a supernumerary marker chromosome in 1/76
      lymphocytes and 34/75 fibroblast metaphases. GTG-banding pattern was consistent
      with the chromosomal region 12pter-12q11. While fluorescence-in-situ
      hybridisation (FISH) with a whole chromosome 12 painting probe confirmed the
      origin of the marker, a chromosome 12 specific alpha-satellite probe did not
      hybridise to it. FISH analysis with a specific subtelomeric probe 12p showed
      hybridisation to both ends of the marker chromosome. High-resolution multicolour
      banding (MCB) studies revealed the marker to be a der(12)(pter-->p12.3::p12.3-
      >pter). Summarising the FISH information, we defined the marker as an inverted
      duplication of 12pter-12p12.3 leading to partial tetrasomy of chromosome 12p. In
      skin fibroblasts, cultured at the patient's age of 1 year and 9 years, the marker
      chromosome was found in similar frequencies, even after several culture passages.
      Therefore, we consider the marker to have a functional centromere although it
      lacks detectable centromeric alpha-satellite sequences. To the best of our
      knowledge, this is the first proven analphoid marker of chromosome 12. Molecular
      genetic studies indicated that this marker is of paternal origin. The finding of
      partial tetrasomy 12pter-12p12.3 in our PKS patient allows to narrow down the
      critical region for PKS.

PMID- 11528502
TI  - N219Y, a new frequent mutation among mut(degree) forms of methylmalonic acidemia
      in Caucasian patients.
AB  - Mutations in the MUT locus encoding for the methylmalonyl-CoA mutase (MCM)
      apoenzyme are responsible for the mut forms of methylmalonic acidemia (MMA). To
      date, 49 different mutations have been identified in mut MMA. Only two frequent
      mutations have been reported in the Japanese population and in African-Americans.
      Here we report a new missense mutation N219Y (731 A-->T) which we found in five
      unrelated families of French and Turkish descent. All the patients exhibited a
      severe mut(degree) phenotype and three of them were homozygotes for N219Y. Direct
      involvement of the mutation in the loss of enzyme activity was demonstrated by
      mutagenesis and transient expression study. Mapping of the mutation onto a three
      dimensional model of human MCM constructed by homology with the Propionibacterium
      shermanii enzyme shows that it lies in a highly conserved secondary structure
      motif and might suggest impaired folding and/or poor stability compatible with
      the mut(degree) phenotype. Finally, a 1% N219Y carrier frequency was observed in
      a French anonymous control population. Thus, N219Y is the first frequent mut
      mutation to be reported in the Caucasian population.

PMID- 11528503
TI  - A 31 bp VNTR in the cystathionine beta-synthase (CBS) gene is associated with
      reduced CBS activity and elevated post-load homocysteine levels.
AB  - Molecular defects in genes encoding enzymes involved in homocysteine metabolism
      may account for mild hyperhomocysteinaemia, an independent and graded risk factor
      for cardiovascular disease (CVD). Although heterozygosity for cystathionine beta
      synthase (CBS) deficiency has been excluded as a major genetic cause of mild
      hyperhomocysteinaemia in vascular disease, mutations in (non-)coding DNA
      sequences may lead to a mildly decreased CBS expression and, consequently, to
      elevated plasma homocysteine levels. We assessed the association between a 31 bp
      VNTR, that spans the exon 13-intron 13 boundary of the CBS gene, and fasting,
      post-methionine load and increase upon methionine load plasma homocysteine levels
      in 190 patients with arterial occlusive disease, and in 381 controls. The 31 bp
      VNTR consists of 16, 17, 18, 19 or 21 repeat units and shows a significant
      increase in plasma homocysteine concentrations with an increasing number of
      repeat elements, in particular after methionine loading. In 26 vascular disease
      patients the relationship between this 31 bp VNTR and CBS enzyme activity in
      cultured fibroblasts was studied. The CBS enzyme activity decreased with
      increasing number of repeat units of the 31 bp VNTR. RT-PCR experiments showed
      evidence of alternative splicing at the exon 13-intron 13 splice junction site.
      The 31 bp VNTR in the CBS gene is associated with post-methionine load
      hyperhomocysteinaemia that may predispose individuals to an increased risk of
      cardiovascular diseases.

PMID- 11528504
TI  - Short tandem repeat (STR) haplotypes in HLA: an integrated 50-kb STR/linkage
      disequilibrium/gene map between the RING3 and HLA-B genes and identification of
      STR haplotype diversification in the class III region.
AB  - We present a dense STR/linkage disequilibrium(LD)/gene map between the RING3 and
      HLA-B loci, reference allelic sizes on the most prevalent HLA haplotypes and
      their allelic frequencies in pedigree founders. This resource will facilitate LD,
      evolution and gene mapping studies, including comparisons of HLA and STR
      haplotypes and identification of HLA recombinants. The map was constructed by
      testing novel and previously reported STRs using a panel of 885 individuals in
      211 families and 60 DNA samples from cell lines and bone marrow donors homozygous
      in the HLA-A, -B and -DR loci selected from over 15 000 entries into the registry
      of Swedish bone marrow donors. We have also analysed the variability of STR
      alleles/haplotypes on the most prevalent HLA haplotypes to identify STRs useful
      for fine mapping of disease genes in the region previously implicated in
      susceptibility to many disorders. The analysis of 40 HLA-A*01, B*0801,
      DRB1*03011, DQB1*0201 haplotypes in homozygous donors showed a surprising
      stability in 23 STRs between the class II recombination hot spot and HLA-B, with
      the average of 1.9% (16/838) variant alleles. However, 40% variant alleles were
      found at the D6S2670 locus in intron 19 of the tenascin-X gene both in the
      families and homozygous donors. The nucleotide sequence analysis of this STR
      showed a complex polymorphism consisting of tetra- (CTTT)(8-18) and penta
      nucleotide (CTTTT)(1-2) repeats, separated by an intervening non-polymorphic
      sequence of 42 bp. The HLA-A1, B*0801, DRB1*03011, DQB1*0201 haplotypes had five
      (CTTT)(14-18)/(CTTTT)(2) variants with a predominant (CTTT)(16) allele,
      implicating the tetranucleotide component as the source of this ancestral
      haplotype diversification, which may be due to the location of D6S2670 in the
      region of the highest GC content in the human MHC.

PMID- 11528505
TI  - Spectrum of mutations and genotype-phenotype analysis in Currarino syndrome.
AB  - The triad of a presacral tumour, sacral agenesis and anorectal malformation
      constitutes the Currarino syndrome which is caused by dorsal-ventral patterning
      defects during embryonic development. The syndrome occurs in the majority of
      patients as an autosomal dominant trait associated with mutations in the homeobox
      gene HLXB9 which encodes the nuclear protein HB9. However, genotype-phenotype
      analyses have been performed only in a few families and there are no reports
      about the specific impact of HLXB9 mutations on HB9 function. We performed a
      mutational analysis in 72 individuals from nine families with Currarino syndrome.
      We identified a total of five HLXB9 mutations, four novel and one known mutation,
      in four out of four families and one out of five sporadic cases. Highly variable
      phenotypes and a low penetrance with half of all carriers being clinically
      asymptomatic were found in three families, whereas affected members of one family
      showed almost identical phenotypes. However, an obvious genotype-phenotype
      correlation was not found. While HLXB9 mutations were diagnosed in 23 patients,
      no mutation or microdeletion was detected in four sporadic patients with
      Currarino syndrome. The distribution pattern of here and previously reported
      HLXB9 mutations indicates mutational predilection sites within exon 1 and the
      homeobox. Furthermore, sequence homology to Drosophila homeobox genes suggest
      that some of these mutations located within the homeobox may alter the DNA
      binding specificity of HB9 while those in sequences homologous to a recently
      identified NLS motif of the human homeobox gene PDX-1 may impair nuclear
      translocation of the mutated protein.

PMID- 11528506
TI  - Clinical and radiographic features of multiple epiphyseal dysplasia not linked to
      the COMP or type IX collagen genes.
AB  - Multiple epiphyseal dysplasia (MED) is a mild chondrodysplasia affecting the
      structural integrity of cartilage and causing early-onset osteoarthrosis in
      adulthood. The condition is genetically heterogeneous. Mutations in the COMP gene
      and in two genes (COL9A2; COL9A3), coding respectively for the alpha2(IX) and
      alpha3(IX) chains of type IX collagen, can cause the autosomal dominant forms of
      MED. Mutations in the DTDST gene have recently been identified in a recessive
      form of MED. However, for the majority of MED cases, the genetic defect still
      remains undetermined. We report a three-generation family with an autosomal
      dominant form of MED, characterised by normal stature, joint pain in childhood
      and early-onset osteoarthrosis, affecting mainly the hips and knees. Based on
      discordant inheritance among affected individuals linkage of the phenotype to the
      COMP, COL9A1, COL9A2, COL9A3 genes was excluded. Our study provides evidence that
      at least another locus, distinct from COL9A1, is involved in autosomal dominant
      MED.

PMID- 11528507
TI  - Incorporation of covariates in multipoint model-free linkage analysis of binary
      traits: how important are unaffecteds?
AB  - When the mode of inheritance is unknown, genetic linkage analysis of binary trait
      is commonly performed using affected-sib-pair approaches. When there is evidence
      that some covariates influence the phenotype, incorporation of this information
      is expected to increase the power of the analysis since it allows (1) a better
      specification of the phenotype and (2) to take into account unaffected subjects.
      Here, we show how to account for covariates in the sibship-oriented Maximum
      Likelihood-Binomial (MLB) linkage method by means of Pearson's logistic
      regression residuals which are computed using phenotypic and covariate
      information on both affected and unaffected subjects. These residuals are
      subsequently analysed as a quantitative phenotype with the corresponding
      extension of the MLB approach which can be used without any assumption on the
      distribution of these residuals. Then, a large simulation study is performed to
      study the relative power of incorporating or not unaffected sibs. To this aim,
      two different strategies in the multipoint analysis of family data are compared:
      (1) using residuals of the whole sibships (ie both covariate and genotypic
      information on unaffecteds is needed), and (2) using affecteds only (no
      information on unaffecteds is needed), under different generating models
      according to genetic and covariate effects. The results show that there is a
      clear increment in the power to detect the susceptibility locus when making use
      of the information carried by unaffecteds, in particular for dominant mode of
      inheritance and when values of the covariates influencing the disease are shared
      by all the members of the family.

PMID- 11528509
TI  - Replication and extension studies of inflammatory bowel disease susceptibility
      regions confirm linkage to chromosome 6p (IBD3).
AB  - Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the
      intestine, commonly diagnosed as either ulcerative colitis (UC) or Crohn's
      disease (CD). Epidemiological studies have consistently shown that both genetic
      and environmental factors influence the pathogenesis of IBD. A number of genome
      scans have been conducted in cohorts of IBD families with affected sibling pairs
      (ASPs) to identify chromosomal regions that harbour IBD susceptibility genes.
      Several putative linked loci have been identified, including two loci on
      chromosomes 16 and 12, IBD1 and IBD2, which have subsequently been replicated by
      independent region-specific studies. We have conducted both a replication study
      on another linkage region, chromosome 6p (IBD3), and extension studies on two
      other regions, chromosomes 3p and 7q. Microsatellite markers across each region
      were genotyped in 284 IBD ASPs from 234 families. A nonparametric peak multipoint
      LOD score of 3.0 was observed near D6S291, replicating the previous linkage to
      chromosome 6p (IBD3). Nominal evidence of linkage was observed at both the 3p and
      7q regions.

PMID- 11528508
TI  - A genome screen for multiple sclerosis in Sardinian multiplex families.
AB  - The prevalence of multiple sclerosis in Sardinia is significantly higher than in
      neighbouring Mediterranean countries, suggesting that the isolated growth of the
      population has concentrated genetic factors which increase susceptibility to the
      disease. The distinct HLA association of multiple sclerosis in Sardinia supports
      this interpretation. We have performed a whole genome screen for linkage in 49
      Sardinian multiplex families using 327 markers. Non parametric linkage analysis
      of these data reveal suggestive linkage in the region of Chr 1q31, Chr 10q23 and
      Chr 11p15.

PMID- 11528510
TI  - Familial Mediterranean fever: prevalence, penetrance and genetic drift.
AB  - FMF is widely distributed in populations inhabiting the Mediterranean basin. It
      is mainly attributed to five founder mutations (M680I, M694V, M694I, V726A,
      E148Q) in the MEFV gene. The frequencies and distribution of these mutations in
      146 FMF patients, of Arab and Jewish descent, were compared to that observed in
      1173 healthy individuals of pertinent ethnic groups. Five mutations accounted for
      91% of FMF chromosomes in our patients. Mutation M694V, predominant in North
      African Jews, was observed in all patients other than Ashkenazi Jews; mutation
      V726A was prevalent among all patients other than North African Jews; mutations
      M694I and M680I were mainly confined to Arab patients. Overall carrier rates, for
      four mutations (M680I, M694V, V726A, E148Q), were extremely high in our healthy
      cohort composed of Ashkenazi (n=407); Moroccan (n=243); Iraqi Jews (n=205); and
      Muslim Arabs (n=318); calculated at 1 : 4.5; 1 : 4.7; 1 : 3.5 and 1 : 4.3
      respectively. The V726A allele prevalent among Ashkenazi and Iraqi Jews and
      Muslim Arabs (carrier rates: 7.4, 12.8 and 7.3%, respectively) was not found
      among Moroccan Jews. The M694V allele detected among Moroccan and Iraqi Jews and
      Muslim Arabs (carrier rates 11.1, 2.9 and 0.6%, respectively) was not observed
      among Ashkenazim. The overall frequency of mutations V726A and E148Q in
      Ashkenazim, Iraqi Jews and Arabs indicates that the bulk of individuals that
      comply with the genetic definition of FMF remain asymptomatic.

PMID- 11528511
TI  - Haplotype analysis of the myotonic dystrophy type 1 (DM1) locus in Taiwan:
      implications for low prevalence and founder mutations of Taiwanese myotonic
      dystrophy type 1.
AB  - Myotonic dystrophy type 1 (DM1) is an autosomal dominant neuromuscular disorder
      caused by a CTG trinucleotide expansion at the DM1 locus. In this study, we
      investigated the frequency distribution of various CTG repeats in normal alleles
      and haplotyped the normal and expanded DM1 locus in a group of Taiwanese people.
      In the 496 normal chromosomes examined, up to 18 alleles with different CTG
      lengths from 5 to 30 repeats were found and the frequency of (CTG)(>18) alleles
      was only 1.4% (7/496), predicting a low prevalence of DM1. In addition, there is
      no absolute association between (CTG)(5-19) alleles and Alu insertion/deletion
      polymorphism observed on normal chromosomes. All DM1 alleles examined, however,
      were found to be associated with the Alu insertion. Further detailed genetic
      analysis demonstrated that at least eight haplotypes, including a new haplotype
      (L), were present in the Taiwanese population and that all DM1 alleles were with
      the same haplotype (haplotype A) as that identified in Canadian and Japanese DM1
      populations. These findings support the notion that the out-of-Africa DM1 alleles
      were originated by stepwise expansion from a pool of large-sized normal
      chromosomes with haplotype A.

PMID- 11528512
TI  - TP63 gene mutation in ADULT syndrome.
AB  - TP63 gene mutations have recently been shown to be disease causing in EEC and
      SHFM. Two other overlapping syndromes with ectrodactyly as a major feature, have
      been mapped to chromosome 3q27 close by the TP63 locus, namely the LMS and ADULT
      syndromes. Here, we report on a missense TP63 gene mutation in an isolated ADULT
      syndrome case. This finding widens the spectrum of abnormalities to be ascribed
      to TP63 gene in human and emphasise on the variable roles of the different Tp63
      isotypes.

PMID- 11528513
TI  - A new locus for autosomal dominant Charcot-Marie-Tooth disease type 2 (CMT2F)
      maps to chromosome 7q11-q21.
AB  - Charcot-Marie-Tooth disease (CMT) constitutes a genetically heterogeneous group
      of inherited motor and sensory peripheral neuropathies. The axonal type of CMT is
      designated CMT type 2 (CMT2). Four loci for autosomal dominant CMT2 have been
      reported so far. Only in CMT2E, linked to chromosome 8p21, disease-causing
      mutations in the gene for neurofilament light chain (NEFL) were identified. In
      this study we report a multigenerational Russian family with autosomal dominant
      CMT2 and assign the locus to chromosome 7q11-q21. The CMT2 neuropathy in this
      family represents a novel genetic entity designated CMT2F.

PMID- 11528515
TI  - Cell cycle effects of IL-10 on malignant B-1 cells.
AB  - IL-10 is overexpressed in human chronic lymphocytic leukemia (CLL), and is an
      autocrine growth factor involved in the development of malignant B1 clones in NZB
      mice, a murine model for CLL. Antisense IL-10 oligonucleotide treatment induces
      apoptosis and cell cycle disruption in these cells both in vitro and in vivo. In
      addition, NZB IL-10 knock-out mice fail to develop the B-1 clones. Dampening of
      IL-10 protein production via antisense IL-10 oligonucleotide treatment is
      correlated with decreased p27/Kip1 protein expression which results in increased
      cyclin D2, cyclin E and cyclin A associated kinase activity. The action of the
      antisense oligonucleotides is through alterations in cell cycle regulation,
      resulting in accelerated cell cycle progression, a G2/M block which culminates in
      apoptosis induction in the malignant cells. This implies that the role of IL-10
      as an autocrine growth factor in malignant B-1 cells lies in its ability to
      inhibit apoptosis induction through the maintenance of sustainable cell cycle
      progression in malignant cells.

PMID- 11528516
TI  - Genetic polymorphisms in molecules of innate immunity and susceptibility to
      infection with Wuchereria bancrofti in South India.
AB  - A pilot study was conducted to determine if host genetic factors influence
      susceptibility and outcomes in human filariasis. Using the candidate gene
      approach, a well-characterized population in South India was studied using common
      polymorphisms in six genes (CHIT1, MPO, NRAMP, CYBA, NCF2, and MBL2). A total of
      216 individuals from South India were genotyped; 67 normal (N), 63 asymptomatic
      microfilaria positive (MF+), 50 with chronic lymphatic dysfunction/elephantiasis
      (CP), and 36 tropical pulmonary eosinophilia (TPE). An association was observed
      between the HH variant CHIT1 genotype, which correlates with decreased activity
      and levels of chitotriosidase and susceptibility to filarial infection (MF+ and
      CP; P = 0.013). The heterozygosity of CHIT1 gene was over-represented in the
      normal individuals (P = 0.034). The XX genotype of the promoter region in MBL2
      was associated with susceptibility to filariasis (P = 0.0093). Since analysis for
      MBL-sufficient vs insufficient haplotypes was not informative, it is possible the
      MBL2 promoter association results from linkage disequilibrium with neighboring
      loci. We have identified two polymorphisms, CHIT1 and MBL2 that are associated
      with susceptibility to human filarial infection, findings that merit further
      follow-up in a larger study.

PMID- 11528517
TI  - Interferon-gamma polymorphisms in systemic lupus erythematosus.
AB  - Interferon-gamma is a cytokine which is believed to play a role in both the
      susceptibility and pathogenesis of lupus. To determine whether genetic variants
      might influence the development of this polygenic autoimmune disease, we analyzed
      the gene frequency of eight different alleles in controls and patients with SLE.
      Ninety-nine controls and 136 patients with systemic lupus erythematosus were
      genotyped for a CA repeat in the first intron of the interferon-gamma gene. There
      were no statistically significant differences in the allele frequencies between
      patients and controls suggesting that these polymorphic variants do not influence
      susceptibility. We then examined whether any of these alleles were associated
      with specific clinical manifestations. Allele 1 was associated with
      gastrointestinal lupus while allele 6 was associated with more severe lupus.
      Allele 2 appeared to be protective for arthritis. This suggests that genetic
      variation in interferon-gamma expression might influence the disease course.

PMID- 11528518
TI  - Polymorphisms of Fc gamma-receptors RIIa, RIIIa, and RIIIb in patients with adult
      periodontal diseases.
AB  - Polymorphisms influencing the binding affinity between the Fcgamma receptors and
      IgG of different subclasses are thought to be of importance in the individual
      susceptibility to infections with Gram-negative bacteria contributing to
      periodontal disease. One hundred and fifty-four Caucasian subjects were
      clinically and radiographically examined for their periodontal status and
      genotyped for their allelic pattern of FcgammaRIIa, FcgammaRIIIa, and FcgammaIIIb
      polymorphism. In assessing periodontitis according to mean probing depth and
      attachment loss, no differences were found in allele frequencies or combined
      allotypes between the subjects with mild or moderate and those with severe signs
      of periodontitis. However, the extent and severity of bone loss were
      significantly associated with the genotype of the receptor FcgammaRIIIa. An
      increased risk of severe bone destruction was observed in individuals carrying
      the FcgammaRIIIa-VV genotype (OR = 5.3; 95% CI 1.4-26.2). FcgammaRIIIb is in
      linkage disequilibrium with FcgammaRIIIa. Hence it is also related to periodontal
      disease. There is no indication of an association between the polymorphism of
      FcgammaRIIa and periodontitis. The results are evidence that the FcgammaRIIIa
      genotype coding for the high affinity receptor imposes an additional risk of bone
      loss as does the FcgammaRIIIb genotype coding for the low affinity receptor.

PMID- 11528519
TI  - The T cell regulator gene SH2D2A contributes to the genetic susceptibility of
      multiple sclerosis.
AB  - The T cell specific adapter protein (TSAd) encoded by the SH2D2A gene is involved
      in the control of T cell activation. The gene is located in the 1q21 region,
      which has been implicated in susceptibility to experimental allergic
      encephalomyelitis in the mouse. We therefore evaluated whether a polymorphic GA
      repeat (GA(13)-GA(33)) within the promoter region of the SH2D2A gene shows
      association to multiple sclerosis (MS). The frequency of the short alleles GA(13
      16) was increased among 313 Norwegian MS patients compared to 277 healthy
      controls (0.332 vs 0.249, OR 1.5, Pc = 0.03). Transmission disequilibrium
      analysis in 146 Scandinavian families with at least two affected sibs showed
      increased transmission of GA(16) to MS patients. No linkage or association of MS
      to four genetic markers flanking the SH2D2A gene was observed. After activation
      of naive CD4(+) T cells, T cells homozygous for MS associated short alleles
      displayed lower level of TSAd ex vivo than T cells carrying at least one long
      allele, which were not associated to MS. Since the SH2D2A protein modulates T
      cell activation, this may be a mechanism for how short SH2D2A alleles confer
      susceptibility to develop MS.

PMID- 11528520
TI  - Novel SNPs in the CD18 gene validate the association with MPO-ANCA+ vasculitis.
AB  - Wegener granulomatosis (WG), microscopic polyangiitis (MP), and Churg-Strauss
      syndrome (CSS) are characterized by the presence of anti-neutrophil cytoplasmic
      antibodies (ANCA). Anti-myeloperoxidase (MPO)-ANCA are a typical feature of MP
      and CSS, while anti-proteinase 3 (PRTN3)-ANCA are highly specific for WG. Several
      reports indicate that ANCA may directly contribute to pathological processes, ie,
      through an increase of adhesivity between polymorphonuclear (PMN) and endothelial
      cells (EC). PMN interact and endothelium interact via the adhesion cascade (AC).
      CD18 is a key molecule of the AC, as CD18 defects abrogate the adhesion of PMN
      and cause leukocyte adhesion deficiency, an immunodeficient trait. We have
      screened the entire coding and regulatory regions of the CD18 gene. Ten single
      nucleotide polymorphisms (SNP) were identified, four of them showing significant
      associations with MPO-ANCA(+) vasculitis. One of these SNP's was localized in an
      alternate transcription initiation site. This polymorphism may influence CD18
      gene expression, resulting in dose-dependent increase in adhesion and
      consecutively facilitated degranulation and respiratory burst. In this manner the
      pro-adherent genotype may predispose to MPO-ANCA(+) vasculitis.

PMID- 11528521
TI  - Lack of association of a functionally relevant single nucleotide polymorphism of
      matrix metalloproteinase-1 promoter with systemic sclerosis (scleroderma).
AB  - Matrix metalloproteinase 1 (MMP-1) is necessary for degradation of interstitial
      collagen types I, II, and III, which are the major constituents of the
      extracellular matrix (ECM). Increased expression of MMP-1 has been correlated
      with invasiveness of certain malignancies and cartilage degradation in rheumatoid
      arthritis. Increased transcriptional activity of MMP-1 has been reported with a
      single nucleotide polymorphism (SNP) of the MMP-1 promoter. Systemic sclerosis
      (SSc) is characterized by increased accumulation and turnover of collagen and
      other components of ECM. Previous studies have reported increased expression of
      MMP-1 transcripts in SSc fibroblasts. Therefore, we sought to determine if SSc
      patients with early disease (< or =5 years) from a multi-ethnic cohort were more
      or less likely than ethnically-matched normal controls to have an increased
      frequency of the high promoter activity MMP-1 genotype and whether MMP-1 promoter
      genotypes correlated with any of the major clinical manifestations of SSc. The
      results show that the frequency of the high activity promoter genotype in either
      the heterozygous or homozygous state did not differ significantly between SSc
      patients and ethnically-matched controls, or between SSc patients with either
      diffuse or limited scleroderma. Furthermore, MMP-1 promoter genotypes did not
      significantly correlate with any of the major clinical manifestations of SSc.

PMID- 11528522
TI  - Presence of four major haplotypes in human BCMA gene: lack of association with
      systemic lupus erythematosus and rheumatoid arthritis.
AB  - BCMA (TNFRSF17), along with TACI, has recently been demonstrated to be a receptor
      for BLyS (TNFSF13B). Recent studies indicated substantial role of BLyS signaling
      pathway for systemic lupus erythematosus (SLE). In the present study, we made an
      attempt to screen for polymorphisms of human BCMA, and to test their possible
      association with SLE and rheumatoid arthritis (RA). Two single nucleotide
      polymorphisms (SNPs) were detected within the coding sequence, both of which were
      synonymous substitutions. In addition, two SNPs within the promoter, two SNPs in
      the 5'-untranslated region (UTR), one SNP and one single nucleotide deletion in
      the 3'UTR and four rare variations were detected. From the combination of the
      polymorphisms, it was elucidated that four major haplotypes account for most of
      the genotypes in the Japanese population. Association with SLE and RA was not
      detected, although a slight tendency for the increase of BCMA.03 in SLE was
      observed (P = 0.089). These results indicated that human BCMA is conserved with
      respect to the amino acid sequence, and evidence for association with SLE and RA
      was not observed.

PMID- 11528523
TI  - Different allelic frequencies of several cytokine genes in Hong Kong Chinese and
      Swedish Caucasians.
AB  - It has been shown that cytokine gene polymorphisms are important in the
      regulation of the level of cytokine production that may affect the development
      and extent of inflammatory diseases and transplant rejections. The frequency of
      the -308 TNFA, -383 TNFR1, -1087 IL10 and codon 25 TGFB1 alleles were analysed in
      two different ethnic groups: Chinese from Hong Kong and Caucasians from western
      Sweden. Significant differences in the occurrence of the analysed alleles were
      shown between the two populations. The most profound difference was found in the
      frequency of the A/A genotype at the -1087 position of IL10 gene (18% in
      Caucasians and 89% in Chinese, P < 0.0001, both for the genotype and allele
      frequencies) and less although statistically significant for other investigated
      genes. The noted differences in the frequency of functionally important alleles
      of cytokine genes may have consequences for the mode of appearance and outcome of
      certain diseases in individuals of different ethnicity.

PMID- 11528524
TI  - Novel polymorphisms in the IL-10 related AK155 gene (chromosome 12q15).
AB  - AK155 is a recently discovered cytokine distantly related to IL-10. Its gene is
      located on chromosome 12q15, a region that is likely to harbour susceptibility
      genes for autoimmune and allergic diseases. We provide here identification and
      characterization of two microsatellite polymorphisms at the AK155 locus, i.e.
      D12S2511 and D12S2510. The first is located in the third intron and the second in
      the 3' region of the gene. Both might be useful as markers in association or
      linkage studies of polygenic inflammatory or allergic diseases. No association
      with multiple sclerosis was found for each of these markers by means of the
      transmission disequilibrium test in an extended number of Sardinian simplex
      families.

PMID- 11528525
TI  - Interleukin-4 and interleukin-4 receptor gene polymorphisms in inflammatory bowel
      diseases.
AB  - Imbalances in the regulation of Th1 and Th2 lymphocytes are crucial in
      inflammatory bowel diseases. Interleukin-4 is secreted by Th2 lymphocytes and
      downregulates cytokine production from Th1 lymphocytes. Functionally relevant
      polymorphisms have been described in the interleukin-4 and the interleukin-4
      receptor alpha genes. Association of inflammatory bowel diseases with these
      polymorphisms has been reported recently suggesting high transcription and
      enhanced signalling activity in Crohn's disease. Our study, comprising 211
      patients with Crohn's disease, 147 patients with ulcerative colitis and 446
      healthy controls revealed significant association of Crohn's disease with the 
      590 T allele of the interleukin-4 gene (P = 0.03). This allele entails reduced
      expression of IL-4. The reason for these contrasting findings may be discussed in
      the context of a putatively predisposing allele in linkage disequilibrium with
      the alleles of the interleukin-4 gene.

PMID- 11528527
TI  - Mannose-binding lectin polymorphisms in a Canary Islands (Spain) population.
AB  - We have compared the structural and promoter variants of the mannose-binding
      lectin (MBL) gene in a population from Gran Canaria with that from other
      populations previously reported. The observed frequencies of the seven alleles of
      the MBL gene in our population were: HYPA, 0.24; LYQA, 0.22; LYPA, 0.08; LXPA,
      0.19; LYPB, 0.17; LYQC, 0.03 and HYPD, 0.07. The frequency of non-producer
      alleles and of MBL-deficient individuals in our population is higher than in
      other European and Asian population.

PMID- 11528526
TI  - A novel polymorphism in the pseudogene TCRBV5S5 combines with TCRBV6S1 to define
      three haplotypes.
AB  - In the current study, we report a G to A single nucleotide polymorphism at base
      pair 396 of the TCRBV5S5P gene. This polymorphism has a frequency of 0.20 in a
      cohort of Caucasian controls. In addition, we provide evidence for linkage
      disequilibrium between TCRBV5S5P and the TCRBV6S1 gene.

PMID- 11528528
TI  - Two novel polymorphisms in the human transforming growth factor beta 2 gene.
AB  - We have identified two novel polymorphisms in the transforming growth factor beta
      2 (TGFbeta2) gene; an insertion in the 5'-untranslated region (5'UTR) and a
      single nucleotide polymorphism (SNP) in exon 1. A 895-bp fragment was analysed
      covering part of the 5'UTR and exon 1. Single-strand conformation polymorphism
      (SSCP) analysis of polymerase chain reaction (PCR) products was performed to
      detect sequence variations. This was followed by the sequencing of samples
      demonstrating distinct banding patterns. A 4-bp insertion (ACAA) in the 5'UTR and
      a SNP (G > A) within exon 1 was identified. The 5'UTR polymorphism was found to
      be common in three Caucasian populations from Spain, Turkey and the UK. Exon 1
      polymorphism is rare and results in an R to H amino acid substitution in codon
      91. Both polymorphisms may prove useful for investigating possible associations
      of TGFbeta2 with disease.

PMID- 11528529
TI  - A vascular connection to Alzheimer's disease.
AB  - Alzheimer"s disease (AD) is characterized by a progressive and debilitating
      dementia in elderly people. The causes of this disease are not known, but major
      risk factors include old age and a family history of dementia, Down"s syndrome,
      female gender, low level of education, and head injury. There is no known cure
      for Alzheimer"s disease. The disease is characterized by abnormal accumulation of
      amyloid-beta peptide and the protein Tau in the nerve cells and extracellular
      space of certain regions of the brain. Cerebral amyloid angiopathy is another
      marker for Alzheimer"s disease. In autopsies, small cerebral arterial blood
      vessels and capillaries show signs of inflammation, amyloid accumulations, and a
      focal breach of the blood-brain barrier. This review focuses on the results of
      recent investigations of vascular responses to infusion of amyloid-beta(1-40),
      the means of preventing vascular damage, using a live animal (rat) model, and the
      combination of intravital video recordings of the mesenteric microvascular bed
      with electron microscopic analyses of the same vascular segments. We propose that
      the cerebral vascular changes in patients with Alzheimer"s disease probably
      precede the neuronal damage and dementia.

PMID- 11528530
TI  - Flow in lymphatic networks: interaction between hepatic and intestinal lymph
      vessels.
AB  - OBJECTIVE: Lymph from both the liver and intestine flows into the cisterna chyli.
      We hypothesized that increasing liver lymph flow would increase cisterna chyli
      pressure and, thereby, decrease intestinal lymph flow, potentiating intestinal
      edema formation. METHODS: Anesthetized dogs were instrumented to measure and
      manipulate portal vein pressure and cisterna chyli pressure. The effects of
      directly increasing portal pressure with and without directly increasing cisterna
      chyli pressure on intestinal wet-to-dry ratio and intestinal ascites formation
      rate were determined. Target values for portal and cisterna chyli pressures were
      determined following elevation of inferior vena caval pressure to levels seen in
      patients with obstructive caval disease. RESULTS: Direct elevation of portal
      pressure (P(port)) alone to 17.5 mm Hg caused a significant increase in
      intestinal wet-to-dry ratio (3.98 +/- 0.24 vs. 3.40 +/- 0.43) and the rate of
      ascites formation (0.36 +/- 0.12 vs. 0.05 +/- 0.03 mL/g dry wt/h). Simultaneous
      direct elevation of cisterna chyli pressure to 6.0 mm Hg and P(port) to 17.5 mm
      Hg caused further increases in intestinal wet-to-dry ratio (5.52 +/- 1.20) and
      ascites formation (0.57 +/- 0.11 mL/g dry wt./h). CONCLUSIONS: Inferior vena
      caval hypertension increases liver lymph flow that elevates cisterna chyli
      pressure, which inhibits intestinal lymph flow and augments intestinal edema
      formation.

PMID- 11528532
TI  - An effective and economical solution for digitizing and analyzing video
      recordings of the microcirculation.
AB  - OBJECTIVE: To assemble an economical system for analysis of microcirculation
      movies. METHODS: Images of cremaster microvessels were recorded onto sVHS video
      cassettes. These recordings were digitized onto a Macintosh computer using a
      MiroMotion DC30 plus video compression card and Adobe Premiere software, which
      permits video rate (25-30 fps) capture of full-sized (768 x 576 PAL, 640 x 480
      NTSC) frames. Once captured, images were analyzed using NIH Image software.
      RESULTS: Combination of the Macintosh computer, the MiroMotion card, and Adobe
      Premiere allowed capture of high-resolution images at video rate, with the only
      limitation to sequence length being available hard-drive space. Captured movies
      could be directly accessed using the freely available NIH Image software. Use of
      built-in analysis tools and custom-written macros greatly facilitated rapid,
      accurate, and reproducible analysis of parameters such as blood flow velocity,
      leukocyte rolling velocity, and firm adhesion. CONCLUSIONS: Low-priced hardware
      and software aimed at the home-video enthusiast can be combined with free image
      analysis software to provide a powerful image-analysis solution for study of the
      microcirculation.

PMID- 11528531
TI  - Association between shear stress, angiogenesis, and VEGF in skeletal muscles in
      vivo.
AB  - OBJECTIVE: To investigate the hypothesis that capillary proliferation in skeletal
      muscles, induced by a long-term increase in blood flow which elevates capillary
      shear stress, is associated with capillary expression of vascular endothelial
      growth factor (VEGF). METHODS: Adult rats received prazosin in drinking water (
      approximately 2 mg per day) or had extensor digitorum longus (EDL) muscles
      stimulated by implanted electrodes for up to 14 days. At intervals, serial frozen
      sections of EDL were stained for alkaline phosphatase to identify capillaries,
      proliferating cell nuclear antigen (PCNA), and VEGF-A protein. Shear stress was
      estimated from capillary red blood cell velocities and diameters, measured by
      direct observation of epi-illuminated EDL. RESULTS: Chronic stimulation and
      prazosin treatment both increased capillary: fiber ratio by approximately 40%
      after 14 days. In stimulated muscles, the percentage of capillaries positively
      stained for VEGF increased within 3 to 4 days, while the density of PCNA-positive
      capillaries had increased 20-fold after 2 days. With prazosin, VEGF-positive
      capillaries increased after 2 and 4 days, accompanied by a threefold increase in
      PCNA. By 14 days, PCNA labeling and VEGF were still high in stimulated muscles,
      but no longer different from controls with prazosin. After 3 to 4 days of
      treatment, capillary shear stress in resting muscle was 57% higher than in
      controls as a result of stimulation, but 4 times higher with prazosin.
      CONCLUSIONS: Higher capillary shear stress with prazosin than with stimulation
      may upregulate VEGF expression in the early stages of treatment. Greater
      proliferation of capillaries preceding a higher proportion of VEGF-positive
      capillaries in stimulated muscles, in the presence of a modest increase in shear
      stress, suggests that angiogenesis was initiated by other factors in addition to
      shear stress.

PMID- 11528533
TI  - Vascular dysfunction induced by AGE is mediated by VEGF via mechanisms involving
      reactive oxygen species, guanylate cyclase, and protein kinase C.
AB  - OBJECTIVE: These experiments were designed to elucidate mechanisms mediating
      vascular dysfunction induced by advanced glycation end products (AGEs). METHODS:
      Skin chambers were mounted on the backs of Sprague-Dawley rats and 1 week later,
      granulation tissue that formed in the bottom of the chamber was exposed twice
      daily for 7 days to glycated rat serum albumin in the presence and absence of
      inhibitors of reactive oxygen intermediates, nitric oxide synthase and guanylate
      cyclase, protein kinase C (PKC), and a neutralizing vascular endothelial growth
      factor (VEGF) antibody. Vascular (125)I-albumin clearance and blood flow were
      quantified by use of a double isotope-dilution technique and radiolabeled
      microspheres, respectively. RESULTS: Albumin permeation and blood flow were
      increased dose-dependently to a maximum of 2 to 3 times controls by increasing
      the extent of glucose modification, the concentration, or the duration of
      exposure to glycated albumin. These increases were significantly attenuated by
      probucol and superoxide dismutase; N(G)-nitro-L-arginine-methyl ester (L-NAME), a
      nitric oxide synthase inhibitor; LY83583, a guanylate cyclase inhibitor; and
      LY333531, a beta-isoform-selective protein kinase C inhibitor. A neutralizing
      VEGF monoclonal antibody also markedly attenuated the permeability and blood flow
      increases induced by glycated albumin. CONCLUSIONS: These observations indicate
      potentially important roles for oxygen free-radicals and nitric oxide in
      mediating permeability and blood flow changes induced by glycated proteins via
      mechanisms involving increased protein kinase C activity and VEGF production.
      Striking similarities in the mechanism by which hyperglycemia and glycated
      proteins induce vascular dysfunction suggest that a common pathway mediates
      effects of these different metabolic imbalances on vascular dysfunction.

PMID- 11528534
TI  - Mediation of EDHF-induced reduction of smooth muscle [Ca(2+)](i) and arteriolar
      dilation by K(+) channels, 5,6-EET, and gap junctions.
AB  - OBJECTIVE: To characterize the role of K(+) channels, the cytochrome P-450 (CYP)
      metabolite 5,6-EET, and gap junctions in modulation of arteriolar myogenic tone
      by a non-nitric oxide nonprostaglandin mediator, termed "endothelium-dependent
      hyperpolarizing factor" (EDHF), released to acetylcholine (ACh) in skeletal
      muscle arterioles. METHODS: In isolated rat gracilis arterioles, simultaneous
      changes in smooth muscle (aSM) [Ca(2+)](i) (assessed by changes in fura-2
      ratiometric signal, R(Ca)) and diameter were measured in response to ACh in the
      presence of indomethacin and L-NAME. RESULTS: ACh, the K(ATP) channel opener
      pinacidil, and the Ca(2+) channel inhibitor verapamil elicited comparable
      decreases in aSM [Ca(2+)](i) (max.: -32 +/- 3%, 29 +/- 3%, and -30 +/- 3%,
      respectively) and arteriolar dilations (max.: 90 +/- 4%, 96 +/- 2%, and 95 +/-
      2%, respectively). ACh-induced responses were inhibited by KCl-depolarization,
      K(Ca) channel blockers (TEA, charybdotoxin), or gap junction inhibitors (18alpha
      glycyrrhetinic acid, hyperosmolar sucrose). The K(ATP) channel inhibitor
      glibenclamide, the K(IR) channel inhibitor barium chloride, or the CYP inhibitor
      17-octadecynoic acid (ODYA) were without effect. The putative EDHF analogue 5,6
      EET elicited constrictions in the presence of the endothelium that could be
      prevented by indomethacin or a TxA(2) receptor antagonist, whereas in the absence
      of the endothelium, EDHF elicited only small, charybdotoxin-insensitive decreases
      in aSM R(Ca) and dilations (max.: -8 +/- 2% and 27 +/- 4%, respectively).
      CONCLUSIONS: In skeletal muscle arterioles, EDHF 1) substantially and rapidly
      reduces myogenic tone by decreasing aSM [Ca(2+)](i) via opening K(Ca) channels,
      2) it is unlikely to be 5,6-EET or other CYP metabolites, but 3) requires
      functional gap junctions.

PMID- 11528535
TI  - Distribution of angiotensin II receptor expression in the microcirculation of
      striated muscle.
AB  - OBJECTIVE: The current study was undertaken to localize and identify angiotensin
      II (Ang II) receptor subtypes in the microcirculation of striated muscle.
      METHODS: Cremaster muscles from 7- to 8-week-old Sprague-Dawley rats were
      excised, placed in a dissection solution maintained at 4 degrees C, and 3 branch
      orders of arterioles and venules, as well as capillaries and a muscle specimen,
      were microdissected under a stereomicroscope. Reverse transcription polymerase
      chain reaction (RT-PCR) methods were developed for purification and amplification
      of extremely small amounts of RNA (<5 ng/microL) from whole tissue samples. RNA
      was isolated from each sample, reverse transcribed, and the cDNA products were
      amplified by polymerase chain reactions (PCR) specifically primed with either
      AT(1a), AT(1b), or AT(2) receptor primers. The products were electrophoretically
      size-fractionated on an agarose gel, stained with ethidium bromide to visualize
      DNA bands, and analyzed to determine the presence or absence of AT receptor
      subtypes. Protein expression was confirmed by Western blotting pooled samples
      with specific antiserum. RESULTS: AT(1a) and AT(2) receptors were found in nearly
      all orders of both arterioles and venules, as well as the skeletal muscle
      biopsies. AT(1b) receptors, if present, were only observed on a few instances in
      the arterioles. Furthermore, PCR reactions specifically primed for skeletal
      muscle cell (MHC(2B)) and endothelial cell (eNOS) specific proteins demonstrated
      that there was no cross-contamination between the vessels and the skeletal muscle
      biopsies. CONCLUSIONS: This study describes a unique method for the isolation and
      preparation of microvessels and provides the first data directly demonstrating
      the presence of AT(1) and AT(2) receptors in microvessels as well as in skeletal
      muscle fibers.

PMID- 11528536
TI  - A survey of report writing by neuropsychologists, I: general characteristics and
      content.
AB  - A survey addressing professional practices regarding the content and format of
      reports on clinical neuropsychological assessments was sent to a randomly
      selected sample of 750 US members of Division 40 of the American Psychological
      Association. A total of 414 usable replies were received, yielding a response
      rate of 55%. Although there was widespread agreement between respondents with
      different clinical practices regarding the need to include in reports various
      specific variables (e.g., patient age and education, referral agent and
      question), there was considerable variability with regard to other items. Most
      notably, frequency of comments about prior financial compensation seeking varied
      with patient age group, diagnostic category, and reimbursement source, whereas
      patient age group and (to a lesser extent) psychologist's board certification
      were associated with different habits regarding specification of the utilized
      norms. It is concluded that, although there are many similarities among clinical
      documentations from different sources, the content of neuropsychological reports
      tends to vary with the specific practice parameters of the individual
      neuropsychologist.

PMID- 11528537
TI  - A survey of report writing by neuropsychologists, II: test data, report format,
      and document length.
AB  - Data are presented regarding current practices in the organization of
      neuropsychological reports, based on a representative sample of 414 US members of
      Division 40 of the American Psychological Association. The vast majority of the
      sample included some numeric test data in their reports, either within the text
      or as an addendum. The nature of the most predominant age groups and diagnostic
      categories served by neuropsychologists was of prominent influence on variables
      such as the frequency of utilization of age- and grade-equivalent scores, the
      inclusion of specific diagnostic codes, the provision of narrative
      recommendations, and the practice of deferring report distribution until after
      review with the patient or family. In addition, greater involvement with forensic
      evaluations in a medicolegal context through private practice tended to increase
      length of reports. It is concluded that, although there are many areas of
      consensus in the field with regard to the organization of neuropsychological
      reports, the final product needs to be shaped on the basis of consideration of
      the clinical presentation of the patient as well as the needs and knowledge base
      of the target audience.

PMID- 11528538
TI  - Comparison of premorbid and postinjury mmpi-2 profiles in late postconcussion
      claimants.
AB  - A comparison of premorbid and postinjury MMPI-2 profiles was performed in 23
      patients with mild cranial/cervical injuries. All claimants attributed major
      personality change to their injuries during the course of compensation-related
      neuropsychological examinations. Their premorbid MMPI-2 profiles were all
      abnormal and the modal code-type indicated somatoform psychopathology. The post
      accident MMPI profiles showed continuous somatization trends, but they
      unexpectedly showed (a) increased defensiveness and (b) a general decrease in
      global psychopathology. The findings did not support an 'eggshell plaintiff'
      theory of chronic postconcussive complaints. The view that chronic postconcussive
      complaints require a wider focus on non-neuropsychological factors is enhanced.

PMID- 11528539
TI  - Comparing student and patient simulated malingerers' performance on standard
      neuropsychological measures to detect feigned cognitive deficits.
AB  - Despite the proliferation of studies investigating methods for detecting
      malingering, important questions that remain unanswered. Specifically, many
      studies use students to simulate malingering; however, it is unclear whether this
      is an appropriate analog group. In addition, many studies have focused on the
      development of cognitive measures designed to detect malingering, rather than
      pursuing whether current neuropsychological measures are effective. Results of
      the present investigation suggest that student malingerers are significantly more
      difficult to detect than non-neurological patients instructed to malinger. The
      findings also provide further support for the recent evidence that standard
      neuropsychological measures are useful in detecting malingering.

PMID- 11528540
TI  - Quantitative and qualitative interpretation of neuropsychological data in the
      assessment of temporal lobectomy candidates.
AB  - Neuropsychologists who serve as members of an epilepsy surgery team are often
      asked to provide information regarding localized cerebral dysfunction that may
      relate to the seizure focus in patients with intractable temporal lobe epilepsy
      (TLE). However, the rate at which neuropsychological (NP) assessment results
      correspond with the side of seizure focus (i.e., left vs. right) in TLE patients
      is unknown. The majority of literature in this area has focused on the ability of
      single NP tests to detect lateralized cognitive dysfunction in groups of TLE
      patients, with mixed findings and few consistent replications. The primary
      purpose of this study was to examine the rate at which qualitative clinician
      interpretations of NP profiles agree with seizure lateralization as determined by
      a multidisciplinary surgery team in temporal lobectomy candidates. Quantitative
      analyses of single NP test scores and groups of test scores (i.e., cognitive
      domain composite scores) were also conducted to examine their effectiveness in
      discriminating left from right TLE groups. Only four of the 19 NP test variables
      and three of the nine composite cognitive domain scores significantly differed
      between the groups. However, clinician interpretation of NP profiles agreed with
      the surgery conference team's determination of seizure laterality in two-thirds
      of cases. These findings suggest that qualitative aspects of NP performance play
      an important role in identifying lateralized cerebral dysfunction in TLE
      patients, and provide additional support for the use of NP assessment results in
      the selection of temporal lobectomy candidates.

PMID- 11528541
TI  - Effective screening for Alzheimer's disease among older African Americans.
AB  - Relatively little data exist concerning the utility of brief cognitive measures
      to detect dementia among African Americans. The current study evaluated the
      clinical utility of the Mini-Mental Status Exam (MMSE) and the Fuld Object Memory
      Evaluation (FOME) in detecting Alzheimer's disease (AD) among both African
      American and European American older adults. One hundred and forty geriatric
      patients from a large urban academic medical center were examined. Overall, the
      FOME appeared to be more effective in detecting AD than was the MMSE (93%
      sensitivity vs. 75% sensitivity, respectively), although both measures suffered
      from relatively low specificity (63.5) in the full sample. The FOME demonstrated
      exceptional clinical utility among African American patients (sensitivity 98.3%;
      specificity = 64.5; positive predictive power 83.8%; negative predictive power
      95.2%). The results of this study support the use of the FOME among older African
      Americans to detect dementia.

PMID- 11528542
TI  - Construct validity of the continuous attention test for children.
AB  - The purpose of this study was to evaluate the construct validity of the
      Continuous Attention Test for Children (the CAT), a clinical measure of
      vigilance. To examine convergent and discriminant validity, a multitrait
      multimethod matrix was used. It was predicted that the CAT would correlate with
      other neuropsychological measures involving vigilance, but not with measures
      involving potential confounds (e.g., short-term memory). Participants were 47
      children, aged 6 to 11, referred for neuropsychological assessment. Results
      partially supported discriminant validity, but convergent validity was weak. That
      is, findings suggest that the CAT measures an ability distinct from those
      assessed by some other popular tests involving vigilance. However, method-related
      confounds may remain. The CAT appears to add useful information in the context of
      clinical evaluations.

PMID- 11528543
TI  - Intraindividual variability in cognitive performance in persons with chronic
      fatigue syndrome.
AB  - Studies of cognitive performance among persons with chronic fatigue syndrome
      (CFS) have yielded inconsistent results. We sought to contribute to findings in
      this area by examining intraindividual variability as well as level of
      performance in cognitive functioning. A battery of cognitive measures was
      administered to 14 CFS patients and 16 healthy individuals on 10 weekly
      occasions. Analyses comparing the two groups in terms of level of performance
      defined by latency and accuracy scores revealed that the CFS patients were slower
      but not less accurate than healthy persons. The CFS group showed greater
      intraindividual variability (as measured by intraindividual standard deviations
      and coefficients of variation) than the healthy group, although the results
      varied by task and time frame. Intraindividual variability was found to be stable
      across time and correlated across tasks at each testing occasion. Intraindividual
      variability also uniquely differentiated the groups. The present findings support
      the proposition that intraindividual variability is a meaningful indicator of
      cognitive functioning in CFS patients.

PMID- 11528544
TI  - The WCST-64: a standardized short-form of the Wisconsin Card Sorting Test.
AB  - The Wisconsin Cart Sorting Test (WCST) is a well-established measure of executive
      function. Practical and financial constraints have increased the need for
      abbreviated neuropsychological procedures. A number of abbreviated versions of
      the WCST have been introduced and cogent arguments can be made for one over
      another in certain situations. However, the single deck, 64-card WCST (WCST-64)
      is the most logical and practical short form. Psychological Assessment Resources
      (PAR) has recently published a new manual with comprehensive norms for the WCST
      64. This paper reviews the new product, discusses the comparability of the WCST
      64 and the standard version, and suggests directions for future research.

PMID- 11528545
TI  - Getting into dementia assessment on the "ground floor".

PMID- 11528546
TI  - [History of pediatric oncology in Germany].

PMID- 11528547
TI  - [Treatment of children with acute lymphoblastic leukemias in the German
      Democratic Republic until 1991].

PMID- 11528548
TI  - [Congenital amegakaryocytic thrombocytopenia (CAMT) - a defect of the
      thrombopoietin receptor c-Mpl].
AB  - Congenital amegakaryocytic thrombocytopenia (CAMT) is a very rare bone marrow
      failure syndrome presenting with isolated hypomegakaryocytic thrombocytopenia at
      birth developing into a pancytopenia during the first years of life. Bone marrow
      transplantation is the only curative therapy for this disease so far.
      Thrombopoietin (TPO) is the most important hematopoietic growth factor for the
      regulation of megakaryopoiesis and thrombopoiesis. We investigated TPO production
      and reactivity in CAMT patients. TPO plasma levels were high like in other forms
      of thrombocytopenia due to ineffective megakaryopoiesis. However, we found a
      defective reactivity to TPO: Neither hematopoietic progenitor cells in the bone
      marrow nor platelets from the peripheral blood did respond to TPO. Flow
      cytometric investigations demonstrated a lack of expression of the TPO receptor c
      Mpl on the surface of platelets. Accordingly, we found mutations in the c-mpl
      gene, which are predicted to lead to a complete or at least partial loss of
      function of the TPO receptor. TPO is not only involved in the regulation of
      megakaryocytopoiesis but also in early hematopoiesis. This seems to be the reason
      for the general defect in hematopoiesis in CAMT leading to the development of
      pancytopenia.

PMID- 11528549
TI  - [Improved results in the treatment of acute myeloid leukemia - Results of study
      AML-BFM-93 in East Germany with comparisons to the preceding studies AML-I-82 and
      AML-II-87].
AB  - BACKGROUND: Three multicenter studies were conducted in East Germany on the
      treatment of acute myeloid leukaemia in children. The latest of the three studies
      (AML-BFM-93-OST) was part of the common German study AML-BFM-93. PATIENTS AND
      METHODS: The total number of registered patients was 262. The number and dosage
      of administered chemotherapeutic agents was elevated with each new study.
      RESULTS: Both the remission rate (85 %) and the likelihood of an event free
      survival (52 % after 5 years) could be improved significantly in study AML-BFM-93
      OST. The results of the common German study AML-BFM-93 were identical to those of
      the East German part AML-BFM-93-OST. Compared with international studies it was
      one of the most successful treatment strategies in children with AML. Patients
      who showed toxic side effects to heart, liver, kidneys, skin or nervous system
      during the chemotherapy had a significantly lower risk of relapse, once they
      overcame the intensive therapy. During the five years of study AML-BFM-93-OST,
      treatment results could be improved despite an unchanged therapy strategy. This
      may partly be due to the modernisations and restorations that were carried out in
      many East German hospitals in this time. CONCLUSIONS: The therapy regimen of
      study AML-BFM-93 allowed a substantial improvement in the treatment of children
      with AML. Further intensification of chemotherapy should only be undertaken in
      accordance to the individual sensitivity of each patient.

PMID- 11528550
TI  - Clinical outcome of patients with childhood acute lymphoblastic leukaemia and an
      initial leukaemic blood blast count of less than 1000 per microliter.
AB  - BACKGROUND: One of the strongest predictive factors for therapy outcome in
      childhood acute lymphoblastic leukaemia (ALL), treated according to ALL-BFM
      protocols, is the response to initial prednisone treatment. Prednisone response
      is characterized by the peripheral leukaemic blast count. The threshold value for
      the characterisation as good or poor prednisone response is 1000
      blasts/microliter on day eight of initial prednisone treatment. It is frequently
      being discussed, whether patients with ALL that initially present with < 1000
      blasts/microliter and still show < 1000 blasts/microliter by day eight of
      treatment, have the same therapy outcome as prednisone good-responders with
      initially >/= 1000 blasts/microliter. PATIENTS AND METHODS: We evaluated all
      patients included in the ALL-BFM 90 study showing good prednisone response. This
      group included 660 patients presenting with < 1000 blasts/microliter at
      diagnosis. We compared these patients with the prednisone good-responders that
      initially presented with >/= 1000 blasts/microliter. In addition we analysed all
      patients who showed an increasing blast count within the threshold of 1000
      blasts/microliter by day eight of treatment. RESULTS: Children presenting with
      ALL and < 1000 blasts/microliter at diagnosis showed a small but significantly
      better outcome than prednisone good-responders with initially >/= 1000
      blasts/microliter (5 year pEFS 0.86 vs. 0.81, P value 0.0064). If analyzed by
      treatment group, no significant differences were found. Patients with < 1000
      blasts/microliter on day eight of treatment but increasing blast count from
      diagnosis until day eight did not perform worse. CONCLUSION: The prognostic value
      of the prednisone response is not restricted to childhood ALL patients presenting
      with >/= 1000 blasts/microliter at diagnosis, but retains its strength as a
      strong predictor of treatment outcome also in patients with < 1000
      blasts/microliter at diagnosis.

PMID- 11528552
TI  - Traditional and emerging molecular markers in neuroblastoma prognosis: the good,
      the bad and the ugly.
AB  - BACKGROUND: Neuroblastomas (NB) are a heterogeneous group of childhood tumours
      with a wide range of likelihood for tumour progression. As traditional parameters
      do not ensure completely accurate prognostic grouping, new molecular markers are
      needed for assessing the individual patient's prognosis more precisely. PATIENTS
      AND METHODS: 133 NB of all stages were analysed in blind-trial fashion for
      telomerase activity (TA), expression of surviving, and MYCN status. These data
      were correlated with other traditional prognostic indicators and disease outcome.
      RESULTS AND CONCLUSIONS: TA is a powerful independent prognostic marker for all
      stages and is capable of differentiating between good and poor outcome in
      putative "favourable" clinical or biological subgroups of NB patients. High
      surviving expression is associated with an adverse outcome, but is more difficult
      to interprete than TA because survivin expression needs to be accurately
      quantified to be of predictive value. We propose an extended progression model
      for NB including emerging prognostic markers, with emphasis on telomerase
      activity.

PMID- 11528551
TI  - [Improved treatment results in children with AML: Results of study AML-BFM 93].
AB  - BACKGROUND: In the multicenter trial AML-BFM 93 daunorubicin or idarubicin was
      randomly applied in all patients during induction in combination with cytarabine
      and etoposide. After induction all patients were stratified to the standard or
      high risk group. To improve outcome in high risk patients high dose cytarabine
      and mitoxantrone (HAM) was introduced. The placing of HAM as either the 2nd or
      3rd therapy block was randomized to evaluate the efficacy and toxicity
      accordingly. PATIENTS AND METHODS: 471 children with de novo AML entered the
      trial AML-BFM 93 (161 standard risk, 310 high risk). RESULTS: Overall, 387 of 471
      (82 %) patients achieved remission, 5-year survival, event free survival (EFS),
      and disease free survival were 60 % SE 3 %, 51 % SE 2 % and 62 % SE 3 %,
      respectively. Idarubicin-based induction resulted in a significantly better blast
      cell reduction in the bone marrow on day 15 (25 of 144=17 % patients with > 5 %
      blasts compared to 46 of 149=31 % patients after daunorubicin, pchi(2)=0.01).
      This was, however, mainly seen in high risk patients treated with idarubicin (19
      % vs. 38 %, pchi(2)=0.007). Cardiotoxicity, WHO grade 1 - 3 shortening fraction
      reduction after induction occurred in 6 % patients in both arms. In the total
      group of patients probabilities of five years event-free survival and disease
      free survival were similar for patients treated with daunorubicin or idarubicin.
      However, in patients presenting with more than 5 % blasts on day 15 there was a
      trend for a better outcome after treatment with idarubicin (p logrank 0.06).
      Outcome in high risk patients was superior in study 93 compared to study 87
      (remission rate and 5-year pEFS in study AML-BFM 93 vs. study 87: 78 % vs. 68 %,
      p=0.007, and 44 % vs. 31 %, p logrank=0.01). The placing of HAM as the 2nd or 3rd
      therapy block was of minor importance. However, patients who received the
      daunorubicin treatment during induction benefited from early HAM. CONCLUSION:
      Compared to study AML-BFM 87 treatment results in study AML 93 improved
      significantly in high risk patients. This can partly be contributed to the better
      response on day 15 after idarubicin induction but is mainly due to the
      introduction of HAM.

PMID- 11528553
TI  - [Expression of the neurotrophin-receptor TrkB predicts outcome in
      nephroblastomas: results of a pilot-study].
AB  - BACKGROUND: The neurotrophin-receptor TrkB plays an important role in
      pathogenesis, biology and prognosis of neuroblastoma. Expression of TrkB on
      aggressive neuroblastomas leads to proliferation and survival of the tumor cells
      and is associated with an unfavorable prognosis. It is now known that Trk
      receptors are also expressed in extraneural tissues including the kidney.
      PATIENTS AND METHODS: To study the role of the neurotrophin-receptor TrkB in
      nephroblastoma/Wilms' Tumor (WT), we determined TrkB mRNA expression by
      semiquantitative duplex RT-PCR in 39 primary WT. Comparison of mRNA expression
      levels with clinical variables was performed using Cox regression analysis.
      RESULTS: The 5-year overall survival was significantly worse for patients with
      tumors expressing high levels of a functional TrkB-receptor (TrkBfull) in
      comparison to patients with low levels of TrkBfull (70 % versus 100 %, p=0.005).
      Conversely, children with tumors expressing high mRNA levels of a functionally
      inactive truncated TrkB receptor (TrkBtrunc) had a significantly higher 5-year
      overall survival rate in comparison to patients with low levels of TrkBtrunc (100
      % versus 68 %, p=0.003). The hazard ratios for TrkBfull and TrkBtrunc remained
      significant after adjusting for tumor stage. All WT with high levels of TrkB also
      expressed the ligand brain-derived neurotrophic factor (BDNF). CONCLUSIONS: Full
      length and truncated TrkB appear to be important prognostic factors in WT. Their
      expression should be assessed prospectively in a larger panel of WT and may have
      a future role in patient assignment to risk-based treatment strategies. TrkB
      signaling may be reduced in WT with favorable outcome due to low numbers of TrkB
      receptors or a competitive effect of functionally inactive TrkBtrunc.

PMID- 11528554
TI  - [Hypermethylation as a potential prognostic factor and a clue to a better
      understanding of the molecular pathogenesis of medulloblastoma--results of a
      genomewide methylation scan].
AB  - BACKGROUND: The molecular mechanisms controlling initiation and progression of
      medulloblastomas are largely unclear. Changes in DNA methylation of promoter
      regions have been shown to disturb the expression of growth regulatory genes.
      PATIENTS AND METHODS: We evaluated DNA methylation patterns in 17
      medulloblastomas, 5 stPNETs and 5 medulloblastoma cell lines using Restriction
      Landmark Genomic Scanning (RLGS), a method displaying up to 2.000 potential gene
      loci in a single gene. To test whether previously characterized tumor suppressor
      genes are affected by hypermethylation we performed MS-PCR for p15INK4B,
      p16INK4A, VHL, TP53 and E-cadherin. RESULTS: The analysis of RLGS profiles from
      tumors revealed an abundance of hypermethylation in primary tumors and cell
      lines. Extrapolated to the human genome with its approximately 36,000 genes a
      total of 420 loci become hypermethylated in the tumor genomes. The previously
      characterized medulloblastoma breakpoint cluster in 17p11.2 appears to be a
      hotspot for aberrant methylation. Cox regression analysis of survival data
      identified seven CpG islands for which hypermethylation is suggestive of a poor
      prognosis. MS-PCR analysis of known genes demonstrated hypermethylation of
      p16INK4A in a limited number of tumors. The pattern of DNA hypermethylation was
      similar in medulloblastomas and stPNETs. However, some CpG islands were shown to
      be specific for a tumor type, while others were shared targets. CONCLUSIONS:
      Hypermethylation is a common abnormality in primary medulloblastomas and
      supratentorial PNETs. Several hundreds of CpG islands are potential targets for
      methylation in medulloblastomas including the breakpoint cluster in 17p11.2. The
      methylation status of certain gene sequences appears to be associated with the
      clinical outcome. Promoter hypermethylation has an outstanding potential as a
      marker for the identification of novel tumor suppressors as well as diagnostic
      and therapeutic targets in medulloblastomas.

PMID- 11528555
TI  - Genetic analysis of childhood germ cell tumors with comparative genomic
      hybridization.
AB  - BACKGROUND: Germ Cell Tumors (GCTs) in children and adolescents constitute a
      clinically and histologically heterogeneous group of tumors. Compared to GCTs in
      adults, the numbers of GCTs in children analyzed with cytogenetic and molecular
      genetic techniques is limited. However, the data available to date reveal a
      pattern of cytogenetic aberrations different from that in adults. Comparative
      genomic hybridization (CGH) is a valuable technique for the genetic profiling of
      tumors that allows screening for chromosomal imbalances consistent with
      amplification of oncogenes and loss of putative tumor suppressor genes. As CGH
      does not require tissue culture, it also allows analysing archival tissue
      samples. PATIENTS: This study focuses exclusively on GCTs in children younger
      than ten years of age and summarizes the genetic data of 51 tumors. Eighteen
      teratomas and 33 malignant GCTs were included. Primary sites were the testis
      (n=10), coccyx (n=13), mediastinum (n=20), ovary (n=5), CNS (n=2), and the face
      (n=1). METHODS: The experimental procedure includes differential enzymatic
      fluorescence labeling of tumor and control DNA followed by comparative
      hybridization to normal male chromosomes, karyotyping and computerized analysis
      of the fluorescence profiles. RESULTS: With the exception of one testicular and
      two ovarian tumors, malignant GCTs in children do not show chromosomal gain of
      12p, which is characteristic of GCTs in adult patients. Irrespective of the
      primary site, childhood GCTs show chromosomal imbalances of chromosome 1 (loss of
      distal 1p, gain of 1q), deletion of 4q and 6q as well as gain of 20q at a high
      frequency. CONCLUSIONS: These studies will help guiding further investigations
      elucidating the role of putative tumor suppressor genes at e.g. 1p36 and 6q. In
      addition, further studies incorporated in prospective therapeutic protocols are
      necessary to evaluate the prognostic relevance of specific genetic aberrations.

PMID- 11528556
TI  - [Hematopoietic growth factors in prophylaxis and therapy of infections
      complications in children with neutropenia].
AB  - Hematopoietic colony-stimulating factors have been introduced into clinical
      practice as additional supportive measures to reduce infectious complications
      associated with congenital or acquired neutropenia. Over the past decade, we have
      begun to appreciate the subtler aspects of the proper use of G-CSF and GM-CSF,
      identifying appropriate indications and contraindications. In the course of
      evaluating the corpus of studies, a set of formal recommendations have been
      propagated for the judicious use of these expensive growth factors. To prevent
      serious infection, the use of G-CSF or GM-CSF is recommended in a subset of
      pediatric cancer patients shortly after having received chemotherapy or a form of
      a marrow transplant. Children with highly intensive chemotherapy (e.g., children
      with high risk ALL or NHL) seem to benefit from hematopoietic growth factors
      whereas this is still unclear for children undergoing therapy for solid tumors.
      An exciting development is the use of G-CSF and GM-CSF to mobilize peripheral
      blood progenitor cells for autologous or allogeneic transplantation. In pediatric
      patients with hematological diseases, there are only few data on the use of
      hematopoietic growth factors in children with myelodysplastic syndrome. Experts
      recommend the early administration of G-CSF in children with very severe aplastic
      anemia. The use of G-CSF is also recommended in children with severe chronic
      neutropenia, but these patients have to be monitored regularly for cytogenetic
      abnormalities. No larger study has shown a clinical benefit of hematopoietic
      growth factor in preterm or term infants. Future studies in pediatric patients
      are clearly warranted to address several issues. Prospective clinical trials are
      still needed to define specific treatment groups who can benefit from growth
      factor support. In this regard, efforts must be directed at better defining the
      endpoints and in particular assigning value to reduction in treatment of possible
      infectious complications, such as days in hospital, antibiotic usage and costs.
      In addition, randomized studies are required to evaluate the proper dosage and
      duration of therapy, which most likely will vary between groups of patients. In
      addition, combinations of different growth factors have to be tested,
      particularly if ex vivo expansion and the storage of hematopoietic stem cells are
      to be utilized in a wider spectrum of patients.

PMID- 11528557
TI  - [Cranial irradiation induces premature activation of the gonadotropin-releasing
      hormone].
AB  - BACKGROUND: CNS-irradiation in prepubertal children with leukemia or brain tumors
      can lead to precocious or in high doses to delayed puberty. The underlying
      mechanisms of these disorders are unknown. METHODS: A new animal model of
      experimentally induced pubertal disorders by cranial irradiation has been
      developed. In infantile or juvenile (12 - 23 days old) female rats precocious or
      delayed puberty have been induced by selective cranial Co60-irradiation (4 - 18
      Gy). At age of 32 - 38 days or 3 months relevant hormone parameters have been
      studied basal and after stimulated conditions. RESULTS: Low radiation doses (5 or
      6 Gy) led to accelerated onset of puberty as well as elevated LH- and estradiol
      levels. High radiation doses (9 - 18 Gy) caused retardation of sexual
      development, lower gonadotropin levels and growth retardation associated with
      growth hormone deficiency. After cranial irradiation with 5 Gy the release rates
      of the inhibitory neurotransmitter gamma-aminobutyric-acid (GABA) from
      hypothalamic explants were significantly lower (p < 0,05). The gonadotropin
      releasing-hormone (GnRH) expression in the hypothalamic preoptic area of
      irradiated animals (5 Gy) was significantly higher than in controls (p < 0,05).
      CONCLUSION: The GnRH-pulse generator is very radiosensitive as low dose
      irradiation causes precocious puberty, whereas high dose irradiation is
      associated with delayed sexual maturation. Radiation induced precocious puberty
      might be caused by damage to inhibitory GABAergic neurons leading to
      desinhibition and premature activation of GnRH neurons. Our animal model of
      cranial irradiation seems to be suitable to study neurotransmitter disorders,
      molecular mechanisms and potential preventive intervention of radiation induced
      pubertal changes.

PMID- 11528558
TI  - Obesity after childhood craniopharyngioma--German multicenter study on pre
      operative risk factors and quality of life.
AB  - BACKGROUND: Craniopharyngiomas are tumorous embryogenic malformations. As the
      survival rate after craniopharyngioma is high (92 %), prognosis and quality of
      life (QoL) in survivors mainly depend on adverse late effects such as obesity.
      PATIENTS AND METHODS: We analyzed 214 children and adolescents with
      craniopharyngioma. The records of 185 patients (86 %) were available for
      retrospective analysis of weight profiles and risk factors for obesity. Quality
      of life (QoL) was measured in 145 patients by the Fertigkeitenskala
      Munster/Heidelberg score (FMH) and in 77 patients by PEDQOL questionnaire.
      RESULTS: Eighty-two of 185 patients (44 %) developed severe obesity (body mass
      index [BMI] > 3 SD). Obese patients were compared with 79 patients (43 %) who
      kept normal weight (BMI < 2 SD). No differences between obese and normal weight
      patients were found in terms of gender distribution, age at diagnosis and follow
      up period. However, the BMI SDS at the time of diagnosis was higher (p < 0.0001)
      in patients who developed obesity than in those who did not. Furthermore, obese
      patients presented with bigger tumors (p < 0.05) and a higher rate of a
      hydrocephalus requiring a shunt (p < 0.05) and hypothalamic involvement (p <
      0.05). The mothers of patients who developed severe obesity had a higher BMI (p <
      0.001) at the time of diagnosis. Obese patients had a higher height-SDS at
      diagnosis (p < 0.05) and at the time of last follow-up (p < 0.05) when compared
      with normal weight patients. A prediction model for severe obesity after
      craniopharyngioma was calculated by logistic regression based on the risk
      factors: patient's BMI > 2 SD at diagnosis (p < 0.05; odds ratio: 16.4),
      hypothalamic involvement (p < 0.05; odds ratio: 3.4) and maternal BMI > 25
      kg/m(2) (p < 0.05; odds ratio: 4.6). Significant increases in BMI (p < 0.001)
      occurred during the early post-operative period especially during the first three
      years after diagnosis. FMH percentiles correlated negatively with BMI SDS
      (Spearman r: - 0.37; p < 0.001). Children with craniopharyngioma rated their QoL
      more negative (p < 0.05) in regard to physical abilities, cognitive functioning
      and social functioning when compared with healthy children of the same age group.
      Severely obese patients with craniopharyngioma estimated their QoL lower (p <
      0.05) for all domains except for autonomy, cognition and familial integration in
      comparison with non-obese patients. CONCLUSION: Hypothalamic tumor involvement
      and familial disposition for obesity are risk factors for the development of
      severe obesity in patients with craniopharyngioma. As weight gain starts early
      after diagnosis and severe obesity causes a reduction in QoL, early therapeutic
      efforts should be considered in patients at risk. To confirm our results the
      prospective multicenter study Kraniopharyngeom 2000 on children and adolescents
      with craniopharyngioma was initiated (www.kraniopharyngeom.com).

PMID- 11528559
TI  - [Germ cell transplantation as a tool for fertility preservation of oncological
      patients].
AB  - Spermatogonia are the diploid cells in the testis, representing a small self
      sustaining pool of male germ line stem cells as well as a larger pool of
      differentiating germ cells which enter the process of spermatogenesis. After
      going through prophase of meiosis as spermatocytes these cells finally leave the
      testis as sperm. Spermatogonia share many characteristics with other stem cells
      but also carry some specific physiological features. Many details about the
      kinetics of spermatogonial divisions, about the hormonal regulation of their
      expansion and differentiation and about their clinically relevant involvement as
      a cause for male infertility are poorly understood. However, the loss of
      spermatogonia following chemo- or radiotherapy leading to temporary or permanent
      infertility of the patient is a well known and unwanted site effect of many
      oncological therapies. Isolation and extracorporal storage of spermatogonia prior
      to the treatment and transplantation into the testis after recovery from the
      disease presents a promising future tool for fertility preservation in male
      patients undergoing oncological therapy.

PMID- 11528560
TI  - [Between heaven and hell - children's emotional perception of stemcell
      transplantation].
AB  - The following paper is the manuscript of an oral presentation during the annual
      GPOH meeting on May 22nd, 2000 in Berlin. Following her experiences as a member
      of the psychosocial care team of a children's cancer unit the author discusses
      the emotional impact of stemcell or bone marrow transplantation in children.
      Psychosocial care is identified as a way to support children emotionally during a
      situation of existential crisis, and to help them share their inner feelings and
      experiences.

PMID- 11528561
TI  - The central Scotland Escherichia coli O157:H7 outbreak: risk factors for the
      hemolytic uremic syndrome and death among hospitalized patients.
AB  - Little is known about risk factors for complications of Escherichia coli O157:H7
      infection in adults. The 1996 outbreak in central Scotland involved the largest
      number of adult case patients in whom hemolytic uremic syndrome (HUS) developed
      and, ultimately, the largest number of deaths associated with E. coli O157:H7
      infection that has yet been recorded. We investigated risk factors for HUS in a
      retrospective study of all hospitalized case patients in this outbreak. Of 120
      case patients, 34 had HUS develop, 28 of whom were adults. Sixteen adults died.
      Significant risk factors for HUS were age <15 years or >65 years (odds ratio
      [OR], 4.4; 95% confidence interval [CI], 1.3-14.4), hypochlorhydria (OR, 6.7; 95%
      CI, 1.9-24.0), and coincidental antibiotics (OR, 4.7; 95% CI 1.4-16.5). Factors
      associated with HUS were as follows: white blood cell count >20 x 10(9) cells/L
      (OR, 8.25; 95% CI, 1.1-60.3), neutrophil count >15 x 10(9) cells/L (OR, 8.5; 95%
      CI, 1.5-50.1), and serum albumin level <35 g/L (OR, 7.2; 95% CI, 1.2-42.5) < or
      =3 days after symptom onset. Deaths were confined to case patients >65 years of
      age. Early identification of risk factors for HUS is vital and could select case
      patients for trials of preventative and treatment therapies.

PMID- 11528562
TI  - Rotavirus and central nervous system symptoms: cause or contaminant? Case reports
      and review.
AB  - Rotavirus is a common cause of severe gastroenteritis in children. In 2 patients
      with rotavirus gastroenteritis who developed encephalopathy, rotavirus RNA was
      detected in the cerebrospinal fluid (CSF) by reverse transcription-polymerase
      chain reaction; in 1 patient, rotavirus RNA was detected on 2 occasions 3 weeks
      apart. There are increasing reports of cases in which patients who have seizures
      after an episode of rotavirus diarrhea have evidence of rotavirus in their CSF. A
      search of 2 large hospital discharge databases suggested that seizures are noted
      as part of the discharge diagnosis in the records of, at most, <4% of patients
      with rotavirus diarrhea versus 7% of patients with bacterial diarrhea. Although
      evidence suggesting that rotavirus is a cause of central nervous system sequelae
      remains inconclusive, the 2 case reports presented in this study further
      illustrate a possible association. Further study is required to determine whether
      detection of rotavirus in CSF represents a true pathogen, CSF contamination that
      occurs at the time of lumbar puncture or in the laboratory, or carriage of
      rotavirus RNA in trafficking lymphocytes.

PMID- 11528563
TI  - Risk factors for Acinetobacter baumannii nosocomial bacteremia in critically ill
      patients: a cohort study.
AB  - Nosocomial bacteremia caused by Acinetobacter baumannii (AB) is of increasing
      concern in critically ill patients, and the risk factors for this infection are
      not well established. An inception cohort study in a 40-bed medical and surgical
      intensive care unit (ICU) at a single institution was conducted during a 2-year
      period to determine the risk factors for AB nosocomial bacteremia. Risk factors
      related to the underlying diseases, the clinical picture at admission, and those
      acquired during the stay in the ICU were recorded upon admission and daily
      throughout the ICU stay. We defined an "invasive procedures index" as the number
      of invasive procedures performed every day during the ICU stay before the onset
      of AB bacteremia divided by the number of days in the ICU before the onset of AB
      bacteremia. Risk factors that were independently associated with AB bacteremia
      were immunosuppression, unscheduled admission to the hospital, respiratory
      failure at ICU admission, previous antimicrobial therapy, previous sepsis in the
      ICU, and the invasive procedures index.

PMID- 11528564
TI  - Evolution, incidence, and susceptibility of bacterial bloodstream isolates from
      519 bone marrow transplant patients.
AB  - Bacteria remain an important cause of infection in bone marrow transplants. To
      examine shifts in the etiology and susceptibility of bacterial isolates from
      transplants, we reviewed the incidence and susceptibility of blood isolates
      during a 7-year period. The infection rate fell dramatically during this time.
      Gram-positive organisms were isolated more often than gram-negative organisms,
      but the trend is reversing. Streptococci surpassed staphylococci for 5 years as
      the leading pathogen. Increasing resistance to penicillin, ciprofloxacin, and
      imipenem was noted in Streptococcus species. With the exception of type 1 beta
      lactamase-producing bacteria and Pseudomonas aeruginosa, gram-negative isolates
      remained overall susceptible to ceftazidime. Increased antibiotic prophylaxis
      coincided with the reduction in percentage of infected patients and increase in
      resistance to beta-lactam antibiotics. Mortality attributed to bacteremia was low
      except for infections caused by P. aeruginosa and the Enterobacter, Serratia,
      Citrobacter group. There was no mortality attributable to gram-positive organisms
      such as Staphylococcus aureus and viridans streptococci.

PMID- 11528565
TI  - Tuberculous pericarditis: optimal diagnosis and management.
AB  - Pericarditis is a rare manifestation of tuberculous disease. The appropriate
      diagnostic workup and optimal therapeutic management are not well defined. We
      present 10 new cases of tuberculous pericarditis and review the relevant
      literature. The specific topics addressed are (1) the importance of tissue for
      diagnosis, (2) the optimal surgical management, (3) the role of corticosteroids,
      and (4) the impact of human immunodeficiency virus (HIV) on the management of
      this disease. The cases and the literature suggest that the optimal management
      includes an open pericardial window with biopsy, both for diagnosis and to
      prevent reaccumulation of fluid. Corticosteroids probably offer some benefit in
      preventing fluid reaccumulation as well. The data are inconclusive regarding
      whether open drainage or corticosteroid use prevents progression to constrictive
      pericarditis. No studies have addressed these issues specifically in HIV-positive
      patients, but the 3 HIV-positive patients in our series had an excellent response
      to drainage and antituberculous therapy.

PMID- 11528566
TI  - Respiratory virus infections in pediatric hematopoietic stem cell
      transplantation.
AB  - Respiratory virus infections (RVI) have become an increasingly appreciated
      problem in the hematopoietic stem cell transplant (HSCT) population. A
      retrospective analysis of 274 patients undergoing 281 HSCT at St. Jude Children's
      Research Hospital from January 1994 through December 1997 was performed. Medical
      and clinical laboratory records were reviewed beginning at the onset of
      conditioning through the year following each HSCT, and the analysis was done for
      the first RVI only. Thirty-two (11%) of 281 HSCT cases developed a RVI during the
      first year post-HSCT. The most frequent cause of RVI was human parainfluenza
      virus type 3. Univariate analysis was performed to determine the association
      between risk factors and the cumulative incidence of RVI. Respiratory viruses are
      frequent causes of infections in the first year post-HSCT in the pediatric
      population. Only allogeneic transplant and the degree of acute or chronic graft
      versus host disease were found to be statistically significant risk factors for
      RVI.

PMID- 11528567
TI  - Community-acquired bacterial meningitis in adults: categorization of causes and
      timing of death.
AB  - The relationship between cause and timing of death in 294 adults who had been
      hospitalized with community-acquired bacterial meningitis was investigated. For
      74 patients with community-acquired bacterial meningitis who died during
      hospitalization, the underlying and immediate causes of death were identified
      according to the criteria of the World Health Organization and National Center
      for Health Statistics. Patients were classified into 3 groups: category I, in
      which meningitis was the underlying and immediate cause of death (59% of
      patients; median duration of survival, 5 days); category II, in which meningitis
      was the underlying but not immediate cause of death (18%; median duration of
      survival, 10 days); and category III, in which meningitis was neither the
      underlying nor immediate cause of death (23%; median duration of survival, 32
      days). In a substantial proportion of adults hospitalized with community-acquired
      bacterial meningitis, meningitis was neither the immediate nor the underlying
      cause of death. A 14-day survival end point discriminated between deaths
      attributable to meningitis and those with another cause.

PMID- 11528568
TI  - Human immunodeficiency virus-seronegative adults with extrapulmonary tuberculosis
      have abnormal innate immune responses.
AB  - Extrapulmonary tuberculosis is presumably a marker of underlying
      immunodeficiency, but cytokine response pathways in these patients have not been
      well studied. Cytokine responses of peripheral blood mononuclear cells from human
      immunodeficiency virus-seronegative adults with prior culture-confirmed
      extrapulmonary tuberculosis were compared with those of persons with latent
      Mycobacterium tuberculosis infection. Mitogen-stimulated interferon (IFN)-gamma
      production, interleukin (IL)-12 production, and IFN-gamma receptor- and IL-12
      receptor-mediated cytokine production did not differ between case patients and
      control patients. However, median resting IL-8 production was significantly lower
      in case patients than control patients (8051 vs. 19,290 pg/mL; P=.009). In
      addition, the median tumor necrosis factor (TNF)-alpha response was lower in case
      patients than control patients after stimulation with lipopolysaccharide (833 vs.
      1149 pg/mL; P=.06) and lipopolysaccharide plus IFN-gamma (3301 vs. 4411 pg/mL;
      P=.04). These abnormalities in resting IL-8 and lipopolysaccharide-induced TNF
      alpha production were not associated with IFN-gamma or IL-12 abnormalities and
      were detected up to several years after cure of disease, suggesting an
      abnormality in innate immunity.

PMID- 11528569
TI  - Randomized, placebo-controlled clinical trial of oral azithromycin prophylaxis
      against respiratory infections in a high-risk, young adult population.
AB  - Military Special Forces trainees undergo intense psychological and physical
      stressors that often lead to respiratory infection. During 1998-2000, 477 Navy
      Special Forces trainees were enrolled in a double-blind trial of oral
      azithromycin (1 g given weekly) plus a placebo injection, compared with
      benzathine penicillin G (1.2 million U) plus azithromycin placebo tablets. Among
      the 464 subjects with complete data, 44 developed acute respiratory infection (20
      with pneumonia) during the 2 weeks of most intense training; of these subjects,
      12 (27.3%) had evidence of Chlamydia pneumoniae infection and 7 (15.9%) had
      evidence of Mycoplasma pneumoniae infection. Trainees who received azithromycin
      were less likely than were trainees who received benzathine penicillin G to
      develop acute respiratory infection (risk ratio, 0.50; 95% confidence interval
      [CI], 0.28-0.92) and less likely at the end of training to report episodes of
      breathing difficulty (odds ratio [OR], 0.59; 95% CI, 0.34-1.01) or sore throat
      (OR, 0.66; 95% CI, 0.41-1.05). Compared with benzathine penicillin G prophylaxis,
      weekly oral azithromycin was superior in preventing respiratory infection in this
      population at transient high risk.

PMID- 11528570
TI  - Epidemiology and clonality of community-acquired methicillin-resistant
      Staphylococcus aureus in Minnesota, 1996-1998.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) has emerged among patients in
      the general population who do not have established risk factors for MRSA. Records
      from 10 Minnesota health facilities were reviewed to identify cases of MRSA
      infection that occurred during 1996-1998 and to identify which cases were
      community acquired. Susceptibility testing and pulsed-field gel electrophoresis
      (PFGE) subtyping were performed on available isolates. A total of 354 patients
      (median age, 16 years) with community-acquired MRSA (CAMRSA) infection were
      identified. Most case patients (299 [84%]) had skin infections, and 103 (29%)
      were hospitalized. More than 90% of isolates were susceptible to all
      antimicrobial agents tested, with the exception of beta-lactams and erythromycin.
      Of 334 patients treated with antimicrobial agents, 282 (84%) initially were
      treated with agents to which their isolates were nonsusceptible. Of 174 Minnesota
      isolates tested, 150 (86%) belonged to 1 PFGE clonal group. CAMRSA infections
      were identified throughout Minnesota; although most isolates were genetically
      related and susceptible to multiple antimicrobials, they were generally
      nonsusceptible to initial empirical therapy.

PMID- 11528571
TI  - A trial of acellular pertussis vaccine in hospital workers during the Cincinnati
      pertussis epidemic of 1993.
AB  - The safety and immunogenicity of acellular pertussis (AP) vaccine in outbreak
      control was determined in a randomized, double-blind, controlled trial.
      Participants received AP vaccine (n=102), which contained 25 microg of pertussis
      toxoid (PT) and 3 microg of filamentous hemagglutinin (FHA), or licensed
      meningococcal vaccine (MN; n=97). Local reactions (pain or tenderness, redness,
      swelling, and induration) and systemic reactions (fever, sleepiness or lethargy,
      and irritability) were similar among AP and MN vaccinees. One month after AP
      vaccination, the geometric mean level of IgG anti-PT was 33.1 microg/mL, with 2
      fold increases in 85% of patients and 4-fold increases in 73% of patients; for
      IgG anti-FHA, the respective values were 34.7 microg/mL, 92%, and 63%. After 6
      months of follow-up, no serological evidence of pertussis was seen among
      symptomatic or asymptomatic subjects. However, recent evidence of Bordetella
      pertussis infection before immunization was shown. Thus, AP vaccine was safe and
      immunogenic in adults.

PMID- 11528573
TI  - Reactive arthritis and Reiter's syndrome following an outbreak of gastroenteritis
      caused by Salmonella enteritidis.
AB  - Reactive arthritis and Reiter's syndrome have been reported following
      gastroenteritis. Prevalence studies for these conditions are uncommon, and the
      prevalence of Reiter's syndrome after Salmonella enteritidis infection has not
      been previously reported. After a large outbreak of S. enteritidis
      gastroenteritis, a survey of persons exposed to the implicated food source was
      conducted, and those with reactive arthritis were evaluated for possible risk
      factors. Among 481 persons responding to the questionnaire, 217 cases of S.
      enteritidis gastroenteritis were identified (31 confirmed and 186 clinical cases;
      attack rate, 45%). Twenty-nine percent of the cases had symptoms of reactive
      arthritis, 3% had symptoms of Reiter's syndrome, and 10% had reactive arthritis
      with oral ulcers. Markers for severe illness (diarrhea > or =7 days, emergency
      room visit or hospitalization, and antibiotic treatment) were statistically
      significant but colinear factors associated with reactive arthritis. Increased
      awareness of postdysenteric reactive arthritis and Reiter's syndrome is
      recommended.

PMID- 11528572
TI  - Mass vaccination of children with pertussis toxoid--decreased incidence in both
      vaccinated and nonvaccinated persons.
AB  - During 1979-1995, there was no vaccination against pertussis in Sweden. With the
      aim of studying the epidemiology and transmission of pertussis, mass vaccination
      with pertussis toxoid of children born during the 1990s was instituted in the
      Goteborg area (population, 778,597) in 1995. Infants were offered 3 doses of
      pertussis toxoid combined with diphtheria and tetanus toxoids. Children aged > or
      =1 year were offered 3 doses of pertussis toxoid alone. From June 1995 through
      February 1999, 167,810 doses of pertussis toxoid were given to 61,219 children
      born during the 1990s (56% received 3 doses). The number of Bordetella pertussis
      isolates per year declined from 1214 (1993-1995) to 64 (January 1997 through June
      1999; P<.0001), and hospitalizations due to pertussis declined from 62 to 5
      (P<.0001). Significant decreases in B. pertussis isolates and hospitalizations
      occurred in all age groups, including adults and nonvaccinated infants. Thus,
      mass vaccination of children with pertussis toxoid decreases spread of B.
      pertussis in the population.

PMID- 11528575
TI  - Gardnerella vaginalis isolated from patients with bacterial vaginosis and from
      patients with healthy vaginal ecosystems.
AB  - The differences in the phenotype and genotype of Gardnerella vaginalis isolates
      from patients with bacterial vaginosis (BV) and from patients without BV are
      unknown. In our study, 43 isolates of G. vaginalis were examined for biotype
      (hippurate hydrolysis, lipase, and beta-galactosidase activity), sensitivity to
      metronidazole, and genotype. Of the 117 women visiting the gynecology clinic at
      Rush-Presbyterian-St. Luke's Medical Center who were included in the study, 27.4%
      were found to have BV. G. vaginalis was found in samples from 87.5% of women with
      BV, from 34.0% of women with intermediate BV, and from 26.4% of women with
      healthy vaginal ecosystems. Among patients with G. vaginalis, biotypes 7 and 8
      were isolated from 32% and 20% of patients, respectively. Biotype 5 was
      predominantly associated with a healthy vaginal ecosystem (P=.0004). Biotypes 5
      and 7 were the most resistant to metronidazole. No specific phenotype or genotype
      of G. vaginalis causes BV.

PMID- 11528574
TI  - Atovaquone-proguanil versus mefloquine for malaria prophylaxis in nonimmune
      travelers: results from a randomized, double-blind study.
AB  - Concerns about the tolerability of mefloquine highlight the need for new drugs to
      prevent malaria. Atovaquone-proguanil (Malarone; GlaxoSmithKline) was safe and
      effective for prevention of falciparum malaria in lifelong residents of malaria
      endemic countries, but experience in nonimmune people is limited. In a
      randomized, double-blind study, nonimmune travelers received malaria prophylaxis
      with atovaquone-proguanil (493 subjects) or mefloquine (483 subjects).
      Information about adverse events (AEs) and potential episodes of malaria was
      obtained 7, 28, and 60 days after travel. AEs were reported by an equivalent
      proportion of subjects who had received atovaquone-proguanil or mefloquine (71.4%
      versus 67.3%; difference, 4.1%; 95% confidence interval, -1.71 to 9.9). Subjects
      who received atovaquone-proguanil had fewer treatment-related neuropsychiatric
      AEs (14% versus 29%; P=.001), fewer AEs of moderate or severe intensity (10%
      versus 19%; P=.001), and fewer AEs that caused prophylaxis to be discontinued
      (1.2% versus 5.0%; P=.001), compared with subjects who received melfoquine. No
      confirmed diagnoses of malaria occurred in either group. Atovaquone-proguanil was
      better tolerated than was mefloquine, and it was similarly effective for malaria
      prophylaxis in nonimmune travelers.

PMID- 11528576
TI  - The ethical challenge of infection-inducing challenge experiments.
AB  - Challenge experiments that induce infections in healthy volunteers are an
      important method for initial efficacy testing of candidate vaccines and for study
      of the pathogenesis of infectious diseases. Although these studies can be
      conducted safely for selected infectious diseases that are either fully treatable
      or self-limiting, they raise significant ethical issues. An ethical framework is
      offered for evaluating infection-inducing challenge experiments, which focuses on
      the scientific and public health rationale for conducting these studies, the
      risks that they pose and the ways in which these risks can be minimized, the
      symptoms experienced by healthy volunteers that may cause discomfort or distress,
      the exclusion of vulnerable research subjects, the informed consent process, the
      payment of volunteers, and the use of isolation of volunteers to prevent
      infection of others.

PMID- 11528577
TI  - Tuberculosis and aging: a global health problem.
AB  - Despite the World Health Organization's declaration that the spread of
      tuberculosis is a global emergency and despite the implementation of strong
      tuberculosis-control initiatives, this highly infectious disease continues to
      affect all vulnerable populations, including the elderly population (age > or =65
      years). Tuberculosis in aging adults remains a clinical and epidemiological
      challenge. Atypical clinical manifestations of tuberculosis in older persons can
      result in delay in diagnosis and initiation of treatment; thus, unfortunately,
      higher rates of morbidity and mortality from this treatable infection can occur.
      Underlying illnesses, age-related diminution in immune function, the increased
      frequency of adverse drug reactions, and institutionalization can complicate the
      overall clinical approach to tuberculosis in elderly patients; maintenance of a
      high index of suspicion for tuberculosis in this vulnerable population is, thus,
      undoubtedly justifiable.

PMID- 11528578
TI  - Diagnosis of Strongyloides stercoralis infection.
AB  - Strongyloides stercoralis infects 30 million people in 70 countries. Infection
      usually results in asymptomatic chronic disease of the gut, which can remain
      undetected for decades. However, in patients receiving long-term corticosteroid
      therapy, hyperinfection can occur, resulting in high mortality rates (up to 87%).
      Strongyloidiasis is difficult to diagnose because the parasite load is low and
      the larval output is irregular. Results of a single stool examination by use of
      conventional techniques fail to detect larvae in up to 70% of cases. Several
      immunodiagnostic assays have been found ineffective in detecting disseminated
      infections and show extensive cross-reactivity with hookworms, filariae, and
      schistosomes. Although it is important to detect latent S. stercoralis infections
      before administering chemotherapy or before the onset of immunosuppression in
      patients at risk, a specific and sensitive diagnostic test is lacking. This
      review describes the clinical manifestations of strongyloidiasis, as well as
      various diagnostic tests and treatment strategies.

PMID- 11528579
TI  - Adjunctive immune therapy for fungal infections.
AB  - Fungal infections in immunocompromised patients can pose difficult problems in
      clinical management, because the available antifungal chemotherapy is often
      unable to eradicate the infection in these people. Hence, the use of immune
      modulating therapy to augment impaired host immune responses--and thus enhance
      the efficacy of antifungal drugs--is a reasonable approach to improve the
      prognosis of fungal infections. Advances in biotechnology have produced a variety
      of biological response modifiers with the potential to serve as adjunctive immune
      therapy for the treatment of fungal infections, including cytokines, monoclonal
      antibodies, and cell growth factors. In recent years, immune-modulating therapies
      have been studied in an effort to define their potential use for the treatment of
      fungal infections. Much of the available information on the use of this approach
      is encouraging and invites further investigation--with the caveats that the
      information is mostly anecdotal and that immune-modulating therapy occasionally
      has produced adverse effects.

PMID- 11528580
TI  - Recent events and observations pertaining to smallpox virus destruction in 2002.
AB  - To destroy all remaining stocks of variola virus on or before 31 December 2002
      seems an even more compelling goal today than it did in 1999, when the 52d World
      Health Assembly authorized temporary retention of remaining stocks to facilitate
      the possible development of (1) a more attenuated, less reactogenic smallpox
      vaccine and (2) an antiviral drug that could be used in treatment of patients
      with smallpox. We believe the deadline established in 1999 should be adhered to,
      given the potential outcomes of present research. Although verification that
      every country will have destroyed its stock of virus is impossible, it is
      reasonable to assume that the risk of a smallpox virus release would be
      diminished were the World Health Assembly to call on each country to destroy its
      stocks of smallpox virus and to state that any person, laboratory, or country
      found to have virus after date x would be guilty of a crime against humanity.

PMID- 11528581
TI  - A randomized study of the utility of human immunodeficiency virus RNA measurement
      for the management of antiretroviral therapy.
AB  - To compare frequent measurement with infrequent measurement of human
      immunodeficiency virus (HIV) RNA levels in the management of antiretroviral
      therapy, we conducted a clinical strategy study of 206 HIV-infected patients who
      had <500 CD4 cells/mm(3). Patients were randomized (1.5:1) to undergo frequent
      monitoring (at baseline and every 2 months) or infrequent monitoring (at baseline
      and twice yearly), with CD4 cell counts determined every 2 months. Patients
      received unrestricted antiretroviral therapy. In the primary analysis (at month
      6), the frequent group had a mean HIV RNA reduction (+/- standard deviation) of
      0.93+/-0.79 log(10) copies/mL, versus 0.48+/-0.83 log(10) copies/mL for the
      infrequent group (P=.0002). A trend (P=.1) toward improved survival was seen in
      the frequent group. Given this improved virological response, more frequent HIV
      RNA measurement than is recommended in published guidelines (every 3-4 months)
      may be appropriate.

PMID- 11528582
TI  - Evolution of antifungal susceptibility among Candida species isolates recovered
      from human immunodeficiency virus-infected women receiving fluconazole
      prophylaxis.
AB  - The effect of fluconazole on the susceptibility of Candida isolates recovered
      from women infected with human immunodeficiency virus (HIV) was evaluated in a
      randomized, double-blind, placebo-controlled trial. Women with CD4(+) cell counts
      of < or =300 cells/mm(3) received either fluconazole (200 mg/week) or placebo as
      prophylaxis. The antifungal susceptibility of specimens was evaluated. One
      patient who received fluconazole and 2 patients assigned to placebo had Candida
      albicans isolates recovered that were resistant to fluconazole (MIC, > or =64
      microg/mL). Eleven patients assigned fluconazole and 4 patients assigned placebo
      had non-albicans Candida strains (all Candida glabrata) recovered that were
      resistant to fluconazole. There was significant azole cross-resistance among the
      non-albicans Candida species isolates. Although the rate of azole resistance did
      not significantly increase after fluconazole prophylaxis, there was a trend
      toward more in vitro azole resistance in C. glabrata isolates from patients
      assigned fluconazole. Moreover, the majority of resistant vaginal isolates of
      Candida species were recovered after initiation of open-label fluconazole use.

PMID- 11528583
TI  - Leishmaniasis recidivans recurrence after 43 years: a clinical and immunologic
      report after successful treatment.
AB  - We describe a patient with very late recurring leishmaniasis recidivans from whom
      lesional biopsy samples were obtained during and after topical steroid treatment
      that demonstrated the ability of the host to contain the parasite in the absence
      of therapy. Combination therapy with intralesional sodium stibogluconate and oral
      itraconazole was successful and immunologic data suggest that both CD4(+) and
      CD8(+) T cell subsets had roles in this disease process.

PMID- 11528584
TI  - Prophylaxis failure is associated with a specific Pneumocystis carinii genotype.
AB  - To investigate the possible association between Pneumocystis carinii types and
      various clinical and demographic parameters, we used molecular typing to analyze
      93 bronchoalveolar lavage specimens from patients with P. carinii pneumonia
      (PCP). Multivariate regression analysis revealed an association between being
      infected with a specific P. carinii genotype and receiving anti-PCP prophylaxis
      (odds ratio, 4.4; 95% confidence interval, 1.0-18.6; P=.05), although no
      association with a specific drug was detected.

PMID- 11528585
TI  - Posttravel hepatitis A: probable acquisition from an asymptomatic adopted child.
AB  - We report a case of acute hepatitis A in an adoptive parent that was probably
      acquired from a recently adopted child with asymptomatic, active infection.
      Prospective adoptive parents should be protected against hepatitis A because of
      potential exposure during travel and the risk of unrecognized active infection in
      adopted children.

PMID- 11528586
TI  - Treatment of American cutaneous leishmaniasis with miltefosine, an oral agent.
AB  - There is no recognized oral treatment for American cutaneous leishmaniasis. A
      rising-dose, open-label phase I/II trial of the oral agent miltefosine against
      Colombian cutaneous leishmaniasis was conducted. Seventy-two male Colombian
      soldiers (mean weight, 67 kg) received miltefosine at 50-100 mg/day for 3 weeks
      (for 32 evaluable patients) or at 133-150 mg/day for 3-4 weeks (for 32 evaluable
      patients). The per-protocol cure rate for 50-100 mg/day was 21 (66%) of 32
      patients. The per-protocol cure rate for 133-150 mg/day was 30 (94%) of 32
      patients (P =.01, by use of Fisher's exact test). The historic per-protocol cure
      rate for standard injections of antimony is 93%. "Motion sickness" that did not
      interfere with normal duties was experienced by 40% of patients and was dose
      related. Vomiting and diarrhea were reported on approximately 2% of treatment
      days. In this uncontrolled study of oral miltefosine for treatment of patients
      with American cutaneous leishmaniasis, a dosage of approximately 2.25 mg/kg/day
      for 3-4 weeks was effective and tolerated.

PMID- 11528587
TI  - Late and atypical cytomegalovirus disease in solid-organ transplant recipients.
AB  - Posttransplantation cytomegalovirus (CMV) disease typically occurs 1-4 months
      after solid-organ transplantation. The case definition invariably includes
      unexplained fever for > or =3 days, often with leukopenia. Late and atypical
      presentation of CMV disease has been rarely reported. Five cases of late and
      atypical CMV disease in heart (n = 1), liver (n = 1), and kidney (n = 3)
      transplant recipients occurred within a 4-month period in early 1999. These
      patients presented at a median of 25 months after organ transplantation (range, 6
      months to 22 years). Atypical findings included absence of fever in 3 patients,
      elevated white blood cell counts in 4 patients, and normal platelet counts in 4
      patients. Four patients were at risk for primary CMV infection, and 3 received
      ganciclovir prophylaxis for 3 months. One patients was treated for rejection, and
      2 patients had induction muromonab-CD3 (Orthclone; Orthobiotech). Two of the
      patients had pulmonary CMV disease, but neither of these patients had hypoxia.
      Two patients had enterocolitis, one of whom had chronic colitis for a year. These
      cases may represent a changing epidemiology and clinical presentation of CMV
      disease in solid-organ transplant recipients in an era of changing
      immunosuppression and improved CMV disease prevention in the early
      posttransplantation period.

PMID- 11528588
TI  - Infections caused by Kluyvera species in humans.
AB  - Kluyvera is a relatively newly described genus in the family Enterobacteriaceae
      that infrequently causes infections in humans. The organism has been isolated
      from various clinical specimens, but its significance has not been clearly
      established. In fact, it has been regarded alternatively as saprophytic,
      opportunistic, or pathogenic. Since the redefinition of this genus in 1981, case
      reports of diverse clinical infections occurring under various host conditions
      have been published. Here we present a critical review of all Kluyvera infections
      reported in the literature, along with our experience involving 5 additional
      cases. Most patients received prompt antimicrobial treatment on the basis of
      susceptibility testing, and overall the clinical outcomes were good.
      Antimicrobial agents active against most Kluyvera strains include third
      generation cephalosporins, fluoroquinolones, and aminoglycosides. In contrast,
      the resistance to ampicillin, extended-spectrum penicillins, and first- and
      second-generation cephalosporins is significant. Kluyvera is a potentially
      virulent pathogen that deserves aggressive treatment designed with an awareness
      of the organism's antimicrobial resistance patterns.

PMID- 11528589
TI  - Pulmonary reactions during treatment with amphotericin B: review of published
      cases and guidelines for management.
AB  - Acute respiratory events occasionally have been observed during the infusion of
      amphotericin B. Herein we analyze the 21 cases that have been reported, including
      a fatal reaction observed by us. Some useful guidelines are provided that likely
      will allow treatment to be continued safely for patients who have experienced
      such reactions.

PMID- 11528590
TI  - Association of pulmonary tuberculosis with increased dietary iron.
AB  - To determine whether increased dietary iron could be a risk factor for active
      tuberculosis, dietary iron history and human immunodeficiency virus (HIV) status
      were studied in 98 patients with pulmonary tuberculosis and in 98 control
      subjects from rural Zimbabwe. Exposure to high levels of dietary iron in the form
      of traditional beer is associated with increased iron stores in rural Africans.
      HIV seropositivity was associated with a 17.3-fold increase in the estimated odds
      of developing active tuberculosis (95% confidence interval [95% CI], 7.4-40.6;
      P<.001), and increased dietary iron was associated with a 3.5-fold increase (95%
      CI, 1.4-8.9; P=.009). Among patients treated for tuberculosis, HIV seropositivity
      was associated with a 3.8-fold increase in the estimated hazard ratio of death
      (95% CI, 1.0-13.8; P=.046), and increased dietary iron was associated with a 1.3
      fold increase (95% CI, 0.4-6.4; P=.2). These findings are consistent with the
      hypothesis that elevated dietary iron may increase the risk of active pulmonary
      tuberculosis.

PMID- 11528591
TI  - Expression of the erythrocyte-binding antigen 175 in sporozoites and in liver
      stages of Plasmodium falciparum.
AB  - Screening of a Plasmodium falciparum genomic expression library for antigens
      expressed at the pre-erythrocytic stages resulted in the isolation of a
      recombinant phage (DG249) whose insert corresponded to regions II and III of a
      175-kDa erythrocyte-binding antigen (EBA-175). EBA-175 is a parasite ligand
      implicated in red blood cell invasion. Reverse-transcriptase polymerase chain
      reaction, indirect immunofluorescent antibody test, and Western blot analysis
      confirmed that EBA-175 is expressed not only in blood-stage parasites but also in
      infected hepatocytes and on the sporozoite surface. The presence of EBA-175 on
      pre-erythrocytic parasites enhances the vaccine potential of this antigen by
      adding another target to the immune responses elicited by immunization.

PMID- 11528592
TI  - Immune responses to measles and mumps vaccination of infants at 6, 9, and 12
      months.
AB  - Immunizing infants against measles at the youngest age possible has the potential
      to reduce morbidity and mortality. The ability of infants at 6, 9, or 12 months
      to respond to measles and mumps vaccines was evaluated by measuring T cell
      proliferation, interferon-gamma production, and neutralizing antibody titers
      before and after vaccination. Infants in all age groups had equivalent cellular
      immune responses to measles or mumps viruses, with or without passive antibodies
      when immunized. In contrast, 6-month-old infants without passive antibodies had
      low geometric mean titers of antibody to measles or mumps viruses and low
      seroconversion rates. Geometric mean titers of antibody to measles virus
      increased if infants were revaccinated at 12 months. Six-month-old infants had
      limited humoral responses to paramyxovirus vaccines, whereas cellular immunity
      was equivalent to that of older infants. T cell responses can be established by
      immunization with these live attenuated virus vaccines during the first year,
      despite the presence of passive antibodies.

PMID- 11528593
TI  - Immunization with Haemophilus influenzae type b-CRM(197) conjugate vaccine
      elicits a mixed Th1 and Th2 CD(4+) T cell cytokine response that correlates with
      the isotype of antipolysaccharide antibody.
AB  - Haemophilus influenzae type b (Hib) capsular polysaccharide (PS) induces
      protective antibodies but is T independent and poorly immunogenic in infants.
      Conjugate vaccines of Hib PS linked to proteins, such as CRM(197), increase the
      PS antibody titer and elicit immunologic memory. To define the conjugate-induced
      memory T cell response, 19 adults were immunized with Hib-CRM(197), and antibody
      titers, carrier protein-specific CD4(+) T cell proliferation, and cytokine
      production were measured. Hib-CRM(197) induced PS and CRM(197) antibodies,
      vigorous T cell recall responses, and production of cytokines, including
      interleukin (IL)-2, IL-5, IL-10, and interferon-gamma. There was marked
      variability in PS antibody titer, despite consistent CRM(197)-specific recall
      responsiveness, which correlated with peak IgM and IgA PS antibody titers.
      Correlations were also found between IL-2 and IL-5 and IgA PS antibody levels.
      Hib-CRM(197) induced a rapid increase in CRM(197)-specific memory T cells and
      mixed Th1/Th2 cytokines, which may regulate the isotype and quantity of PS
      antibody.

PMID- 11528594
TI  - Ecologic and biologic determinants of filarial antigenemia in bancroftian
      filariasis in Papua New Guinea.
AB  - The relationship between filarial antigenemia and lymphatic pathology was
      investigated in residents of 11 villages in an area of Papua New Guinea where
      Wuchereria bancrofti is endemic. Antigenemia was determined in 1322 persons by
      means of the Og4C3 antibody capture assay. Prevalence of antigenemia by village
      ranged from 61.7% to 98.2% and did not vary by sex. Antigen level increased with
      transmission potential among the 4 villages with measured transmission potential
      (r(2)=.945; P=.028). Antigenemia was associated positively with age in villages
      with the lowest annual transmission potentials (45 and 404 infective larvae/year;
      P<.001), but was distributed evenly across age groups in villages with increased
      transmission (1485 and 2518 infective larvae/year). These data suggest that
      children and adults have similar worm burdens in areas of high transmission,
      whereas worm burdens in areas of lower transmission increase with age. These
      results may be useful in the design and evaluation of programs aimed at
      eliminating lymphatic filariasis.

PMID- 11528595
TI  - Epidemiology and clinical manifestations of unique Chlamydia trachomatis isolates
      that occupy nonfusogenic inclusions.
AB  - Unique Chlamydia trachomatis strains characterized by multiple nonfusing
      inclusions were recently described. These strains lack evidence of the protein
      IncA in the inclusion membrane and have mutations in the incA gene. This study
      evaluated the epidemiology and clinical manifestations of patients infected with
      nonfusing mutant strains (case patients) and compared them with patients infected
      with wild-type fusing strains (control subjects). Both male and female case
      patients had fewer signs of infection than did control subjects (P=.016 and
      P=.019, respectively). Female case patients also had fewer symptoms of infection
      (P=.02). Median inclusion-forming unit (ifu) counts were lower in male and female
      case patients (P=.045 and P=.135, respectively). Thus, nonfusing strains of C.
      trachomatis more often produce subclinical infections than do normal fusing
      strains and have lower median ifu counts. From a prevention perspective, the data
      underscore the importance of screening programs to detect and treat inapparent C.
      trachomatis infection.

PMID- 11528596
TI  - CD8 T lymphocytes and macrophages infiltrate coronary artery aneurysms in acute
      Kawasaki disease.
AB  - The pathogenesis of coronary arterial inflammation in acute Kawasaki disease (KD)
      is unclear. To test the hypothesis that the KD vascular lesion is an activated T
      lymphocyte-dependent process, immunohistochemical studies were done on coronary
      artery aneurysms from 8 fatal acute KD cases by using antibodies to CD45RO
      (activated or memory T lymphocyte), CD8 (cytotoxic T lymphocyte), CD4 (helper T
      lymphocyte), HAM56 (macrophage), and CD20 (B lymphocyte). Acute KD coronary
      arteritis was characterized by transmural infiltration of CD45RO T lymphocytes
      with CD8 T lymphocytes predominating over CD4 T lymphocytes. Macrophages were
      present primarily in the adventitial layer; B lymphocytes were notably absent.
      These data lend support to the hypotheses that KD results from infection with an
      intracellular pathogen, such as a virus, whose antigens are presented by major
      histocompatibility complex class I molecules, and that CD8 T lymphocytes and
      macrophages are important in the pathogenesis of KD coronary aneurysms.

PMID- 11528597
TI  - Lipopolysaccharide-binding protein increases toll-like receptor 4-dependent
      activation by nontypeable Haemophilus influenzae.
AB  - Nontypeable Haemophilus influenzae (NTHi) is a common cause of respiratory tract
      infections. This study investigated the ability of NTHi to bind
      lipopolysaccharide-binding protein (LBP) derived from respiratory epithelial
      cells and the subsequent stimulation of transfected cells expressing membrane
      bound CD14 and toll-like receptor 2 (TLR2) or TLR4. In the absence of LBP, NTHi
      at high concentrations (100 bacteria/epithelial cell) were required to induce
      signals through TLR2 and TLR4. Flow cytometry showed that NTHi in the stationary
      phase bound more LBP than did log-phase bacteria. Of interest, as few as 1 LBP
      bearing bacterium/cell induced strong signaling through TLR4. In contrast, LBP
      bound to NTHi did not promote any increased signaling mediated by TLR2, compared
      with NTHi without LBP. These data suggest that, upon NTHi infection, low numbers
      of bacteria binding LBP may activate TLR4-bearing cells, such as alveolar
      macrophages, and consequently induce an inflammatory response.

PMID- 11528598
TI  - Intracellular cytokine production by fetal and adult monocytes.
AB  - BACKGROUND/PURPOSE: In light of the neonate's increased susceptibility to
      systemic infection, the authors hypothesized that adult and fetal monocytes have
      different cytokine expression profiles in response to lipopolysaccharide (LPS),
      and interleukin (IL)-11, a counter-inflammatory cytokine. METHODS: Samples of
      cord blood (n = 30) and adult blood (n = 30) were obtained and treated as
      follows: control (baseline expression), LPS exposure, and IL-11 or IL-11+LPS
      exposure. After incubation with a protein transport inhibitor, mononuclear cells
      were stained for intracellular tumor necrosis factor (TNF)-alpha, IL-1beta, IL-6,
      and IL-8. Each sample was then analyzed by flow cytometry for cytokine
      expression. Cytokine production was measured by the percent positive as well as
      the fluorescence index for each cytokine. Analysis of variance (ANOVA) and
      Students t tests were used for statistical analysis. RESULTS: Baseline levels of
      IL-8 were significantly higher for fetal monocytes (P <.0001). After LPS
      exposure, fetal monocytes produced less TNF-alpha (P =.0105) and more IL-8 (P
      <.0007) relative to adult cells. IL-11 treatment reduced baseline production of
      IL-8 in fetal and adult monocytes (P <.05). CONCLUSIONS: These results suggest
      that neonatal monocytes portray a different cytokine expression profile compared
      with adult monocytes. IL-11 treatment appears to alter the IL-8 expression of
      resting fetal and adult monocytes.

PMID- 11528599
TI  - Hemodynamic effects of positive end-expiratory pressure during partial liquid
      ventilation in newborn lambs.
AB  - BACKGROUND/PURPOSE: The aim of this study was to compare the effect of positive
      end-expiratory pressure (PEEP) application on hemodynamics, lung mechanics, and
      oxygenation in the intact newborn lung during conventional ventilation (CV) and
      partial liquid ventilation (PLV) at functional residual capacity (FRC). CV or PLV
      modes of ventilation do not affect hemodynamics nor the optimum PEEP for
      oxygenation. METHODS: Seven newborn lambs (1 to 3 days old) were instrumented to
      measure pulmonary hemodynamics and airway mechanics. Each lamb was used as their
      own control to compare different modes of ventilation (CV followed by PLV) under
      graded variations of PEEP (4, 8, 12, and 16 cm H(2)O) on the influence on
      pulmonary blood flow and pulmonary vascular resistance. RESULTS: There was a
      significant drop in pulmonary blood flow (PBF) from baseline (PEEP of 4 cm H(2)O
      on CV, 1,229 +/- 377 mL/min) in both modes of ventilation on a PEEP of 16 cm
      H(2)O (CV, 750 +/- 318 mL/min v PLV, 926 +/- 396 mL/min, respectively; P <.05).
      Peak inspiratory pressure (PIP) was higher on PLV at PEEP states of 4 cm H(2)O
      (16.5 +/- 1.3 cm H(2)O to 10.6 +/- 2.1 cm H(2)O; P <.05) and 8 cm H(2)O (18.8 +/-
      2.2 cm H(2)O to 15.1 +/- 2.6 cm H(2)O; P <.05) when compared with CV. Conversely,
      PIP required to maintain the pCO(2) was lower on PLV at PEEP states of 12 (22.5
      +/- 3.6 cm H(2)O to 24.2 +/- 3.8 cm H(2)O; P <.05) and 16 cm H(2)O (27.0 +/- 1.6
      cm H(2)O to 34.0 +/- 5.9 cm H(2)O; P <.05). CONCLUSIONS: Hemodynamically, CO is
      impaired at a PEEP above 12 cm H(2)O in intact lungs. PFC at FRC does provide an
      advantage in lung mechanics more than 10 to 12 cm H(2)O of PEEP by decreasing the
      amount PIP needed to achieve the similar levels of gas exchange and minute
      ventilation, implying a reduced risk for barotrauma with chronic ventilation.
      Thus, selection of the appropriate level of PEEP appears to be important if PLV
      is to be utilized at FRC. The best strategy for PLV, including the selection of
      PEEP, remains to be determined.

PMID- 11528600
TI  - Prevention of ventilator-induced lung injury with partial liquid ventilation.
AB  - BACKGROUND/PURPOSE: Pulmonary injury from mechanical ventilation has been
      attributed to application of excess alveolar pressure (barotrauma) or volume
      (volutrauma). The authors questioned whether partial liquid ventilation (gas
      ventilation of the perfluorocarbon filled lung, PLV) would reduce ventilator
      induced lung injury. METHODS: A tracheostomy tube and carotid artery catheter
      were placed in anesthetized Sprague-Dawley rats (500 +/- 50 g). Bovine serum
      albumin (BSA) labeled with Iodine (I) 125 was administered intraarterially.
      Ventilation with tidal volume (TV) of 5 mL/kg was initiated. The rats were then
      selected randomly to a 30-minute experimental period of one of the following
      ventilation protocols: continued atraumatic gas ventilation (GV, TV, 5 mL/kg; n =
      10); atraumatic gas ventilation combined with intratracheal administration of 10
      mL/kg perfluorocarbon (GV-PLV, TV, 5 mL/kg, n = 10); barotrauma (BT, peak
      inspiratory pressure [PIP], 45 cm H(2)O; n = 10); barotrauma with PLV (BT-PLV,
      PIP, 45 cm H(2)O; n = 8); volutrauma (VT, TV, 30 mL/kg; n = 8); or volutrauma
      with PLV (VT-PLV, TV, 30 mL/kg; n = 10). Animals were killed and the amount of
      radiolabeled BSA in both lungs was measured and normalized to the counts in 1 mL
      of blood from that animal (injury index). Data were analyzed by analysis of
      variance (ANOVA) with post-hoc t test comparison between groups. RESULTS: There
      was a significant difference in the (125)I-BSA injury index when all groups were
      compared (P <.001 by ANOVA). Post-hoc analysis showed a significant decrease in
      the injury index when comparing BT versus BT-PLV (P =.024) and VT versus VT-PLV
      (P =.014). CONCLUSION: (125)I-BSA leak produced during high-pressure or high
      volume mechanical ventilation is reduced by partial liquid ventilation.

PMID- 11528601
TI  - Noncervicofacial atypical mycobacterial lymphadenitis in childhood.
AB  - BACKGROUND/PURPOSE: Atypical mycobacterial (AM) lymphadenitis is common in
      children but rarely occurs outside the cervicofacial region. The authors report
      their experience in the diagnosis and management of noncervicofacial AM
      lymphadenitis. METHODS: A retrospective review was conducted of cases diagnosed
      at our institution between January 1976 and December 1999, based on positive
      culture of atypical mycobacteria or consistent histology with supportive skin
      testing. RESULTS: Thirty-seven patients were identified over the 23-year review
      period. The median age was 4.3 years (range, 8 months to 13 years and 5 months),
      with 19 boys and 17 girls. The median duration of symptoms was 4 weeks, and the
      most commonly affected sites were the inguinal region (n = 17), axilla (n = 8),
      and lower limb (n = 6). Preceding local trauma was described in 10 patients and a
      viral illness in 4. Laboratory culture for atypical mycobacteria was positive in
      22, and skin testing suggestive in 21 and equivocal in 2. Treatment was by
      excision in 28 and drainage with or without curettage in 9. At a median follow-up
      of 19.7 months, disease had recurred in 4 patients, none of whom had been treated
      initially by excision. CONCLUSIONS: Atypical mycobacterial infection is an
      uncommon cause of noncervicofacial lymphadenitis in children. It typically
      presents with a 4-week history of painless regional lymphadenopathy that may
      follow penetrating trauma. If untreated, the overlying skin becomes involved with
      a violaceous discoloration, and ulceration may occur. Definitive treatment
      involves complete surgical excision, preferably before suppuration extending
      beyond the involved lymph nodes.

PMID- 11528602
TI  - The effect of amnio-allantoic fluid pH on the intestines: an experimental study
      in the chick embryo gastroschisis model.
AB  - BACKGROUND/PURPOSE: Prolonged exposure to amniotic fluid causes the intestinal
      changes such as serosal edema, thickening, fibrous coating, and adhesions in
      gastroschisis. The effect of amnio-allantoic fluid (AAF) pH on intestines was
      evaluated using a chick embryo gastroschisis model. METHODS: Seventy fertile eggs
      were divided into 5 groups: preliminary study (PS, n = 20), AAF control (AAC, n =
      10), just gastroschisis (JG, n = 10), gastroschisis pretreated with placebo (GPP,
      n = 15), and gastroschisis pretreated with sodium bicarbonate (GPS, n = 15). The
      PS group was also divided into 2 subgroups to determine the biochemical
      differences between the amniotic and the allantoic fluid. Gastroschisis was
      created surgically at the 14th day of incubation. In GPS group, 8.4% NaHCO(3)
      solution (0.1 mL/100 mg/d) was instilled into the AAF for 4 days. RESULTS: A
      significant decrease in intestinal damage was observed both macroscopically and
      microscopically in the group GPS compared with the JG and GPP groups.
      CONCLUSIONS: Pretreatment with alkalization of AAF prevented intestinal damage
      because of gastroschisis. Alkalization could be a simple alternative for
      pretreatment with amniotic fluid exchange for human fetuses with gastroschisis.

PMID- 11528603
TI  - Conservative management of mesenchymal hamartomas of the chest wall.
AB  - Mesenchymal hamartomas of the chest wall are rare benign lesions usually
      discovered in infancy. The authors present their experience with 3 cases. All of
      these cases were managed initially conservatively, although 1 child required a
      thoracotomy and partial tumour resection at 5 months of age because of
      respiratory compromise. The other 2 children have now reached 5 and 6 years of
      age with the tumors becoming less prominent. The authors believe many cases can
      be managed conservatively because malignant change has not been reported, and the
      lesions often become relatively smaller as the child grows.

PMID- 11528604
TI  - Multidisciplinary behavioral treatment of defecation problems: a controlled study
      in children with anorectal malformations.
AB  - BACKGROUND/PURPOSE: The most frequent consequences of being born with an
      anorectal malformation (ARM) are problems with fecal continence and constipation,
      which can have various negative implications. In this prospective, controlled
      study the effect of multidisciplinary behavioral treatment dealing with these
      problems is evaluated. METHODS: The effect of multidisciplinary behavioral
      treatment was studied in 24 children (15 boys, 9 girls; mean age 5.8 years).
      Thirteen children were allocated to the treatment condition. The 11 children
      allocated to the waiting list control group also were treated after a waiting
      period of 6 months. Children underwent follow-up after treatment. RESULTS:
      Compared with a waiting list control group, the experimental treatment group
      scores significantly better on 2 important measures ("Templeton," "Percentage of
      feces in toilet"). Although young children had poorer scores than older children
      before treatment, no significant differences in the favorable outcome of
      treatment were found between both groups after treatment. No effect of type of
      ARM on treatment was found either. The results of multidisciplinary behavioral
      treatment remain stable over a mean follow-up period of 7 months. CONCLUSION:
      Multidisciplinary behavioral treatment is an important and valuable supplement to
      the standard medical treatment of children born with ARM suffering from chronic
      defecation problems.

PMID- 11528605
TI  - Fourteen-year experience of acetylcholinesterase staining for rectal mucosal
      biopsy in neonatal Hirschsprung's disease.
AB  - BACKGROUND/PURPOSE: Acetylcholinesterase (AChE) staining of rectal mucosal biopsy
      specimens is the most important and popular examination for making a definite
      diagnosis of Hirschsprung's disease. This examination often is performed for
      patients with constipation in the daily clinic. The results of this examination
      are reflected immediately in the treatment. However, the authors sometimes
      encountered difficult cases to diagnose, especially in neonates. Therefore, a
      retrospective investigation was conducted on the benefits and problems of AChE
      staining of rectal mucosal biopsy specimens in neonates. METHODS: The authors
      encountered 459 cases (91 neonates) of suspected Hirschsprung's disease,
      clinically, from April 1986 to March 2000. Mucosal specimens were taken by punch
      biopsies. Samples were stained by the modified Karnovsky Roots method using
      rubeanic acid as an amplifier and immediately examined with a light microscope.
      These results were collected and assessed mainly on neonatal cases. The authors
      also analyzed the 104 cases of Hirschsprung's disease diagnosed in patients less
      than 1 year of age to evaluate the relationship between the grade of
      proliferation of AChE positive fiber and age. RESULTS: Forty-one neonatal cases
      of Hirschsprung's disease were diagnosed based on the findings of AChE staining.
      A definite diagnosis of Hirschsprung's disease was confirmed based on the
      pathologic findings of operative samples. Forty-eight cases that were diagnosed
      as normal included 4 cases that turned out to be false-negative (3
      Hirschspurung's disease cases and 1 case of an allied disorder of Hirschsprung's
      disease). There were no major complications in mucosal punch biopsy. In the cases
      of Hirschsprung's disease diagnosed in a patient less than 1 year of age, the
      grade of AChE-positive fiber tended to increase with the aging of patients.
      CONCLUSIONS: The specificity of AChE staining was high (100%), but its
      sensitivity was slightly low (91%). Careful long-term follow-up is required for
      any cases diagnosed as normal. Mucosal biopsies should be repeated in cases of
      persistent clinical symptoms.

PMID- 11528606
TI  - Solo-RBT: a new instrument for rectal suction biopsies in the diagnosis of
      Hirschsprung's disease.
AB  - BACKGROUND/PURPOSE: Preoperative histochemistry on rectal mucosal-submucosal
      specimens is the most important step in the diagnosis of Hirschsprung's disease
      and other dysganglionoses. Today, rectal mucosal-submucosal biopsy specimens are
      obtained by suction with the widely used tool first designed by Noblett in the
      late 1960s. The authors developed a new instrument, for which a patent has
      already been filed, for one-hand execution of rectal suction biopsies, which will
      make this operation easier and faster. METHODS: The authors modified the old tool
      but maintained the cutting method described by Noblett. The authors' innovative
      automatic tool (Solo-RBT) is based on the possibility of sequencing suction and
      cutting of the rectal mucosa just by pressing a "trigger." The trigger activates
      a plunger to obtain the vacuum necessary for the suction and a cutter for mucosal
      sampling. To perform a correct biopsy in children with different weight and in
      adults, Solo-RBT can be adjusted suitably to obtain automatically the vacuum
      required in each case. Additionally, this tool is provided with 2 different sizes
      of both capsules and cutters, and it can be disassembled completely for easy
      cleaning, maintenance, and sterilization. RESULTS: The instrument was tested
      clinically on 62 children (189 biopsies), and it proved to be versatile,
      atraumatic, and extremely handy, because it can be used by just 1 physician who
      only needs to press the trigger to obtain the biopsy. CONCLUSIONS: Solo-RBT not
      only maintains the benefits (atraumatic, easy to use, rapid) and the main
      characteristic (cutting system) of Noblett's tool but it also improves its
      features and eliminates most of its disadvantages. Therefore, Solo-RBT represents
      a significant improvement in the diagnosis of Hirschsprung's disease and other
      dysganglionoses.

PMID- 11528607
TI  - Fistula-in-ano in infants: is nonoperative management effective?
AB  - PURPOSE: Recently, a number of studies have reported positive results from the
      nonoperative management of fistula-in-ano in infancy, although it has not been of
      use in all patients. The purpose of this study was to discern the effective
      treatment methods of fistula-in-ano in infants. METHODS: A retrospective review
      was done of 310 children who required operative management for fistula-in-ano or
      perianal abscess between January 1991 and July 2000. Eighteen patients displayed
      an onset of symptoms at less than 1 year of age and a duration of symptoms longer
      than 12 months. The authors analyzed these patients' medical records. RESULTS:
      All patients were boys. The mean duration of the symptoms was 26.6 +/- 27.5
      months. Fourteen patients had shown an onset of symptoms at less than 6 months of
      age. The longest duration was 10 years. The patients showed conservative periods
      of over 12 months because their parents did not want them to undergo surgery. The
      disease in these patients followed 2 patterns. One (6 patients) was an onset of
      symptoms followed by a silent fistula-in-ano state. The other (12 patients) was
      an onset of symptoms followed by an intermittent relapse of inflammation. All
      patients underwent fistulotomy, and none of them had recurrent fistula during the
      follow-up period. CONCLUSIONS: Although the advantages of a nonoperative
      management of fistula-in-ano in infants include the avoidance of general
      anesthesia and surgical intervention, the lesions cannot be cured by a period of
      conservation. Surgical management is more effective in respect to the time
      factor.

PMID- 11528608
TI  - Mapping loci causing susceptibility to anal atresia in pigs, using a resource
      pedigree.
AB  - BACKGROUND/PURPOSE: Very little information on the genetic background for anal
      atresia (anorectal malformations; AA) in humans has been described. A strikingly
      similar natural anomaly occurs in piglets. The authors have used this as an
      animal model for various research purposes. The affected piglets were treated
      surgically soon after birth, raised, and used for breeding. The authors have
      generated a resource pedigree segregating for this naturally occurring
      nonsyndromal AA and describe here the first attempt to map susceptibility loci by
      marker analysis. METHODS: A pig pedigree with a high incidence of AA has been
      established by selective breeding using 3 probands from the Landrace and Large
      White breeds. It has been maintained by intrafamilial crossing for more than 15
      years. A backcross pedigree has now been generated by mating 4 AA females to an
      unaffected male from the Chinese Meishan breed. F(1) animals were both
      intercrossed and backcrossed to affected AA animals. A genome scan was carried
      out using the F(0), F(1), and affected backcross progeny. Ninety-two
      microsatellite loci were analyzed using fluorescently labelled primers and an
      ABI377 sequencer. Linkage analysis was done with the CRI-MAP 2.4 software.
      RESULTS: Crossing affected parents increased the incidence of abnormalities from
      30% to 61.9%. All 39 F(1) pigs were unaffected. In the F(1) intercross, only 3 of
      205 (1.5%) were affected, whereas 42 of 523 (8.0%) backcross progeny were
      affected. The marked difference in the incidence of affected progeny in the F(1)
      intercross and in the backcross indicates the presence of multiple genes causing
      AA. The genome scan showed suggestive evidence for the presence of a
      susceptibility locus on pig chromosome 15 (lod score 2.7 for a pig microsatellite
      marker SW2072). CONCLUSIONS: The results clearly show that AA has a oligogenic or
      polygenic background. The genome scan showed one suggestive locus causing AA on
      pig chromosome 15. The long-term goal is to identify causative genes for this
      malformation by comparative positional candidate cloning. This study provides,
      for the first time, linkage mapping of nonsyndromal anorectal malformations with
      a polygenic inheritance.

PMID- 11528609
TI  - Three quantitative approaches to the diagnosis of abdominal pain in children:
      practical applications of decision theory.
AB  - BACKGROUND/PURPOSE: The authors compared 3 quantitative methods for assisting
      clinicians in the differential diagnosis of abdominal pain in children, where the
      most common important endpoint is whether the patient has appendicitis. Pretest
      probability in different age and sex groups were determined to perform Bayesian
      analysis, binary logistic regression was used to determine which variables were
      statistically significantly likely to contribute to a diagnosis, and recursive
      partitioning was used to build decision trees with quantitative endpoints.
      METHODS: The records of all children (1,208) seen at a large urban emergency
      department (ED) with a chief complaint of abdominal pain were immediately
      reviewed retrospectively (24 to 72 hours after the encounter). Attempts were made
      to contact all the patients' families to determine an accurate final diagnosis. A
      total of 1,008 (83%) families were contacted. Data were analyzed by calculation
      of the posttest probability, recursive partitioning, and binary logistic
      regression. RESULTS: In all groups the most common diagnosis was abdominal pain
      (ICD-9 Code 789). After this, however, the order of the most common final
      diagnoses for abdominal pain varied significantly. The entire group had a pretest
      probability of appendicitis of 0.06. This varied with age and sex from 0.02 in
      boys 2 to 5 years old to 0.16 in boys older than 12 years. In boys age 5 to 12,
      recursive partitioning and binary logistic regression agreed on guarding and
      anorexia as important variables. Guarding and tenderness were important in girls
      age 5 to 12. In boys age greater than 12, both agreed on guarding and anorexia.
      Using sensitivities and specificities from the literature, computed tomography
      improved the posttest probability for the group from.06 to.33; ultrasound
      improved it from.06 to.48; and barium enema improved it from.06 to.58.
      CONCLUSIONS: Knowing the pretest probabilities in a specific population allows
      the physician to evaluate the likely diagnoses first. Other quantitative methods
      can help judge how much importance a certain criterion should have in the
      decision making and how much a particular test is likely to influence the
      probability of a correct diagnosis. It now should be possible to make these
      sophisticated quantitative methods readily available to clinicians via the
      computer.

PMID- 11528610
TI  - Acute abdominal symptoms and signs in children and young adults with spina
      bifida: ten years' experience.
AB  - BACKGROUND/PURPOSE: Diagnosis and management of the acute abdomen in patients
      with spina bifida (SB) can be problematic. There are at least 4 clinical factors
      that can predispose to the development of acute abdominal symptoms and signs, and
      patients with a thoracic level lesion can have a partially insensate abdomen. The
      authors analyzed their accumulated experience to determine the annual incidence
      of acute abdominal signs and symptoms in children and young adults with spina
      bifida, the differential diagnosis, the operative management, and the outcome.
      The pertinent literature was reviewed. METHODS: Cases were ascertained during a
      10-year period at 1 institution and reviewed retrospectively. RESULTS: Twenty-two
      episodes of acute abdominal symptoms and signs in 19 children and young adults
      with SB were ascertained over 10 years at 1 institution, for an annual incidence
      of 0.74%. More patients had a thoracic level lesion (n = 12; 60%) than in the
      clinic population as a whole (27%; P =.04), but the gender distribution was
      similar (58% girls), as was the prevalence of ventriculoperitoneal shunts (VPS;
      95%). The median age was 13 years (range, 1 year to 26 years). Hospitalization
      was necessary for 19 (86%) of the 22 episodes. The duration of symptoms before
      diagnosis was a median of 3 days (range, 1 to 14 days). Most patients (82%)
      presented with abdominal pain. Fever was present in 27%, shock in 23%, and
      peritoneal signs in 23%. There were 14 different final diagnoses, 10 (71%) of
      which were associated with a predisposing factor. Of the 22 episodes, 18 (82%)
      could be attributed to an underlying factor: (1) neurogenic bladder (9; 41%); (2)
      neurogenic bowel (3; 14%); (3) VPS (4; 18%); (4) complications from previous
      surgery (2; 9%). Thirteen patients (59%) underwent a total of 20 surgical
      procedures of 12 different kinds. Despite awareness of the complexities involved,
      3 patients (14%) died: 1 from complications resulting from bladder perforation; 1
      from urosepsis and shock; and 1 from peritonitis caused by VPS infection.
      CONCLUSION: The differential diagnosis of the acute abdomen in patients with SB
      is broad, conditions requiring surgery are frequently diagnosed, and the
      mortality rate is substantial, despite aggressive management.

PMID- 11528611
TI  - Minimal pelvic fluid in blunt abdominal trauma in children: the significance of
      this sonographic finding.
AB  - PURPOSE: The aim of this study was to evaluate the significance of the
      ultrasonographic finding of pelvic fluid after blunt abdominal trauma in children
      as a predictor of an abdominal organ injury. METHODS: The clinical and imaging
      data of 183 children with blunt abdominal trauma were reviewed retrospectively.
      All children had an abdominal sonography as the primary screening study. The
      ultrasound results were divided into 3 groups: group A, normal examination; group
      B, pelvic fluid only; group C, peritoneal fluid outside the pelvis. The results
      of the initial ultrasound examinations were compared with the findings of the CT
      scan, or a second ultrasound examination or the clinical course during the
      hospitalization. RESULTS: Group A included 87 children; group B, 57, and group C,
      39. Four abdominal organ injuries were missed by the ultrasound examination. The
      sensitivity and specificity of the ultrasound examinations to predict organ
      injury in presence of peritoneal fluid outside the pelvis were, respectively,
      89.5% and 96.6%; the positive and negative predictive value were 87.2% and 97.3%.
      No statistically significant difference was seen between group A and group B,
      whereas the presence of peritoneal fluid outside the pelvic cavity (group C) was
      associated strongly with an organ injury (P <.001). CONCLUSIONS: A normal
      ultrasound examination or the presence of pelvic fluid are associated with a low
      probability of an organ injury. In the presence of peritoneal fluid outside the
      pelvis, the probability of an organ injury is very high.

PMID- 11528612
TI  - Biliary atresia associated with meconium peritonitis caused by perforation of
      small bowel atresia.
AB  - BACKGROUND/PURPOSE: This report describes our experiences with 5 cases of biliary
      atresia associated with meconium peritonitis caused by perforation of small bowel
      atresia. METHODS: A review of medical records was undertaken in an effort to
      recognize cases of biliary atresia associated with meconium peritonitis. RESULTS:
      Five patients of 171 with biliary atresia (2.9%) were detected to have meconium
      peritonitis caused by perforation of small bowel atresia. The biliary atresia was
      not suspected during the initial operation for meconium peritonitis. Total
      parenteral nutrition (TPN) made it difficult to make an early differential
      diagnosis of biliary atresia because of the presence of TPN-associated
      cholestatic jaundice, and the Roux-en-Y limb used for hepatic portoenterostomy
      could not be made long enough to prevent cholangitis caused by preexisting short
      bowel. The main complications were severe, intractable cholangitis, short bowel
      syndrome with malnutrition; TPN-associated liver injury; and wound problems. Two
      patients died of ascending cholangitis, 1 patient of liver failure that was
      exacerbated by TPN-associated liver injury, and 1 patient is awaiting a liver
      transplant. Only 1 patient is in good health, being anicteric and showing normal
      growth and development. CONCLUSIONS: Biliary atresia is evidently closely
      associated with meconium peritonitis caused by perforation of small bowel
      atresia. The management of these patients is more difficult than that of patients
      with the usual form of biliary atresia, because of the necessity for a long
      period of TPN and the combined short bowel syndrome. The ideal management of
      these conditions has yet to be determined.

PMID- 11528613
TI  - Laparoscopic cholecystectomy: effective treatment for chronic abdominal pain in
      children with acalculous biliary pain.
AB  - BACKGROUND/PURPOSE: Acalcular biliary pain is a term used to identify patients
      who have significant abdominal pain related to an abnormally low gallbladder
      ejection fraction in the absence of cholelithiasis. Little is known about this
      disease in the pediatric population. The aim of this study was to determine
      whether laparoscopic cholecystectomy is an effective method for treatment of
      children with abdominal pain in the setting of acalcular biliary pain and whether
      one can predict the outcome preoperatively. METHODS: The charts of all children
      who underwent laparoscopic cholecystectomy for acalcular biliary pain in our
      institution from January 1991 through April 1998 were reviewed. Sixty-three
      patients were identified as children with acalcular biliary pain who underwent
      laparoscopic cholecystectomy. Forty-eight patients were contacted successfully
      and they all completed the questionnaire. Complete resolution of abdominal pain
      occurred in 72%, and another 18% had near-complete resolution of pain. Some
      improvement was noted by 8%, and only 2% had no improvement. In a multiple
      logistic model, none of the variables were significant predictors of response
      outcome. CONCLUSIONS: Laparoscopic cholecystectomy is an effective means of
      therapy for children with abdominal pain and low gallbladder ejection fraction.
      It is difficult to predict patients with complete response based on the
      preoperative clinical findings.

PMID- 11528614
TI  - Acute food bolus impaction without stricture in children with gastroesophageal
      reflux.
AB  - BACKGROUND/PURPOSE: This report identifies a group of children in whom severe
      acute food bolus impaction (AFBI) was the leading symptom of gastroesophageal
      reflux (GER) in the absence of stricture. METHODS: The esophageal structure and
      function of 8 patients treated for AFBI requiring endoscopic removal of
      alimentary foreign bodies in 6 of them (up to 4 times in 1 case) were
      investigated by barium meal, esophagoscopy-biopsy, pH-metering, pull-through
      stationary manometry, and 24-hour ambulatory manometry. The results were compared
      with those in a group of age-matched regular refluxers (n = 14) without AFBI.
      RESULTS: Six boys and 2 girls aged 108 +/- 59 months had impaction. Six children
      had symptoms of GER like vomiting during infancy, heartburn, or respiratory tract
      disease. Barium swallow ruled out stenosis in all patients and showed small
      hiatal hernias in 3. All had endoscopic and histologic esophagitis (moderate to
      severe in 6), and one had Schatzki ring. All but one (who had 8.45 mm Hg) had
      normal lower esophageal sphincter pressure (16.2 +/- 4.7 mm Hg, mean +/- SD), and
      all showed normal sphincteric relaxation. Esophageal body motility was not
      significantly different from that in regular refluxers except in 6 children in
      whom energetic distal peristalsis after reflux episodes could be seen
      particularly during the night. Three of them had amazingly powerful distal waves
      during the day and even stronger, simultaneous, wide and bizarre-shaped waves
      during sleep. Symptoms improved in all cases after antireflux medication. Four
      patients were cured after antireflux surgery. CONCLUSIONS: AFBI is a dramatic but
      practically unheard of symptom of GER in children. It should be differentiated
      from dysphagia and reveals motor dysfunction, sometimes severe, of the esophageal
      body in the absence of sphincteric obstruction. Antireflux medication or surgery
      were uniformly successful in our patients.

PMID- 11528615
TI  - Retching and vomiting in neurologically impaired children after fundoplication:
      predictive preoperative factors.
AB  - BACKGROUND/PURPOSE: In neurologically impaired children, retching and recurrent
      vomiting are common after Nissen fundoplication. The aim of this study was to
      identify whether there are preoperative factors that predict their occurrence.
      METHODS: Twenty neurologically impaired children (8 boys, 12 girls; age range, 3
      months to 8 years) were studied prospectively by taking a detailed history of
      behaviors and symptoms associated with feeding before and after Nissen
      fundoplication for gastroesophageal reflux. RESULTS: Preoperatively, children
      could be classified into 2 groups. Children in group A had symptoms suggestive of
      only gastroesophageal reflux (effortless "vomiting" or regurgitation), whereas
      children in group B exhibited one or more features associated with activation of
      the emetic reflex (pallor, sweating, retching, forceful vomiting).
      Postoperatively 0 of 8 in group A retched compared with 8 of 12 in group B (P
      <.005, Fishers Exact test). CONCLUSIONS: Children at high risk of retching, and
      ultimately vomiting, after antireflux surgery may be identified clinically
      preoperatively. They have symptoms that are specifically caused by activation of
      the emetic reflex rather than to gastroesophageal reflux. In these cases,
      antireflux surgery could be considered inappropriate and hence be avoided.

PMID- 11528616
TI  - Esophageal motor dysfunction persists in children after surgical cure of reflux:
      an ambulatory manometric study.
AB  - BACKGROUND/PURPOSE: Esophageal dysmotility shown by perfusion manometry in
      children with gastroesophageal reflux can be primary or acquired. This study
      examines by combined ambulatory pH-metry and manometry the nature of motor
      dysfunction and whether it improves after surgical cure of reflux. METHODS:
      Sixteen refluxing children aged 131 +/- 54 months were studied by combined
      ambulatory pH-metry and manometry before and more than 6 months after successful
      fundoplication. pH-metric and manometric variables were compared at both time end
      points by paired statistical tests accepting a significance level of P less
      than.05. RESULTS: Operation cured all patients clinically and pH-metrically, but,
      in spite of this, only the frequency of motor sequences decreased significantly
      after the operation from 1 (0.45) to 0.8 (0.6) waves per minute (median
      [interquartile range]). Wave amplitude and duration were similar in both
      conditions; the proportion of peristaltic waves was normal and did not change
      before and after the operation (79.5% [17.25] v 81.4% [21.5]; not significant),
      whereas the proportions of complete (63.2% [17.5] v 67.8% [19.3]; not
      significant) and effective (32.4% [31.95] v 27.25% [22.5]; not significant) waves
      were definitely low and remained so after treatment. CONCLUSIONS: The esophagus
      of children with GER has mild disturbances of peristaltic activity with waves
      often incomplete, weak, and scarcely effective. Dismotility does not improve
      after successful fundoplication suggesting that it could be a primary phenomenon.

PMID- 11528617
TI  - Complications of percutaneous endoscopic gastrostomy with or without concomitant
      antireflux surgery in 96 children.
AB  - BACKGROUND/PURPOSE: A study was conducted of the complications of percutaneous
      endoscopic gastrostomy (PEG) with or without antireflux surgery (ARS). METHODS: A
      retrospective review was conducted of all patients, receiving a PEG in the period
      January 1993 through December 1997. Patients' characteristics including
      underlying disease, indications, results of preoperative screening, and
      complications were recorded. PEG placement was performed with the Seldinger
      technique and, in some cases, under laparoscopic control. In the event of a
      pathologic pH study during preoperative screening, laparoscopic antireflux
      surgery (ARS) was added. RESULTS: Mean age was 5 years and 10 months. The
      majority of the children were mentally retarded. The main indications for PEG
      were vomiting, food refusal, inability to swallow, and aspiration. Fifty-nine
      patients had PEG without ARS. Nineteen of these patients had concomitant
      laparoscopy. Thirty-seven patients had PEG with ARS. One patient died
      postoperatively of gastric leakage. PEG-related complications occurred in 31% of
      the patients. There was a significant higher incidence of complications in the
      group of patients that underwent ARS together with PEG compared with PEG
      placement without ARS. Roughly half of the complications were peristomal
      infection related to the use of T-fasteners and the other half gastroduodenal
      obstruction caused by the balloon of the gastrostomy catheter, both preventable
      complications. Preoperative vomiting without a positive pH-study disappeared in
      most cases after PEG placement. Although the pH study normalized in 34 of 37
      patients after concomitant ARS, vomiting persisted in 7 of 17 patients. PEG
      improved the nutritional status in 75% of the children. CONCLUSIONS: PEG improved
      the nutritional status in the majority of the children. However, PEG placement
      can lead to a considerable amount of complications, especially when combined with
      ARS. ARS together with PEG is successful in treating GER but does not necessarily
      cure preexistent vomiting. PEG alone cures vomiting in 80% of the patients and
      rarely leads to vomiting. There seems no good reason for combining PEG with ARS.
      Only if symptoms progress after PEG, ARS should be considered. Caretakers and
      patients should be well informed before placement.

PMID- 11528618
TI  - High-dose omeprazole in esophagitis with stenosis after surgical treatment of
      esophageal atresia.
AB  - The authors describe 4 children with recurrent stenosis and persistent
      esophagitis after secondary repair of a long gap esophageal atresia. They
      underwent an esophageal reconstruction by elongation of the lesser gastric
      curvature according to Scharli at the age of 11 to 14 months. All had esophagitis
      grade III to IV (Savary-Miller classification), esophageal stenosis, and failure
      to thrive. Effective treatment of the esophagitis and prevention of stenosis
      consisted in high doses of omeprazole (1.9 to 2.5 mg/kg/d). After this treatment,
      the need for esophageal dilatation disappeared, and nutritional status
      normalized.

PMID- 11528619
TI  - Phenotypic presentation and outcome of esophageal atresia in the era of the Spitz
      classification.
AB  - PURPOSE: The aim of this study was to investigate contemporary patterns of
      presentation and outcome in newborns with esophageal atresia with or without
      tracheoesophageal fistula (OA) using modern prognostic criteria to appraise
      survival. METHODS: Over a 12-year period (1986 through 1997), 134 patients with
      OA were admitted to a single institution. Patient demographics, the presence of
      cardiac defects, other associated abnormalities (VACTERL), surgical intervention,
      and patient outcome were recorded. To identify and evaluate changes in the
      pattern of clinical presentation, frequency of associated anomalies and outcome,
      patients were analyzed during 4 consecutive time periods, 1986 to 1988, 1989 to
      1991, 1992 to 1994, and 1995 to 1997. RESULTS: A primary repair or delayed
      primary repair was performed in 113 (84%) patients, with a staged procedure in 19
      (14%). Two babies with trisomy 18 did not undergo surgery. Thirty-eight newborns
      (28%) had a major cardiac malformation (excluding patent ductus arteriosus,
      unless needing ligation), and 25 (19%) had recognized VACTERL associations. There
      was a significant increase in the proportion of infants with major cardiac
      defects diagnosed over the study period, 5 of 34 patients between 1986 and 1988
      to 19 of 41 patients between 1995 and 1997 (chi(2) test, P <.001), but the
      incidence of VACTERL associations remained unchanged. Overall survival rate was
      86% in those who underwent surgery. The relative risk of mortality in patients
      with major cardiac disease and VACTERL associations was 3.47 (95% CI; 1.51 to
      7.96) and 2.54 (95% CI; 1.14 to 4.86), respectively. Birth weight was
      significantly higher in infants who survived (2.68 kg) compared with those who
      died (2.16 kg, P =.003). Thirty percent of infants with more than one system
      abnormality died compared with 8% of infants with 1, system abnormality (P
      =.004). CONCLUSIONS: This study has found a significant increase in the frequency
      of cardiac abnormalities encountered in a cohort of OA patients during the period
      under review. Cardiac disease and multiple abnormalities carried a substantial
      increased risk of mortality. In the era of the Spitz classification, the
      phenotypic presentation is important to accurately assess caseload severity and
      prognosis.

PMID- 11528620
TI  - Neonatal perforation of a Y-shaped sigmoid duplication.
AB  - Tubular colonic duplications are exceedingly rare; the "Y"-shaped forms are
      exceptional. In the absence of associated low vertebral or urogenital
      malformations (often fistulas), the tubular colonic malformations frequently stay
      hidden for several years until a complication develops. The authors report a case
      of a spontaneous perforation of a Y-shaped tubular colonic duplication during the
      neonatal period.

PMID- 11528621
TI  - Postpneumonectomy syndrome in children: advantages and long-term follow-up of
      expandable prosthesis.
AB  - BACKGROUND/PURPOSE: Pneumonectomy in children can be complicated by a severe
      mediastinal shift, which leads to bronchial stretching resulting in severe
      respiratory failure. This postpneumonectomy syndrome can be corrected by
      inserting a prosthesis in the empty side of the chest. METHODS: Forty-two
      children, from 6 months to 15 years old, underwent a pneumonectomy. Seven of
      these patients were treated surgically for severe manifestations of
      postpneumonectomy syndrome. First insertion of an expandable prosthesis was
      followed up in 5 cases by its replacement with a breast prosthesis in
      adolescence. The expandable prosthesis was injected periodically with saline
      solution to maintain the mediastinum in a midline position as the children grew.
      RESULTS: The mean delay between pneumonectomy and first prosthesis implantation
      was 5 years (range, 11 months to 8 years). Pulmonary function tests showed a
      substantial improvement in the obstructive syndrome in all patients except one,
      in whom the functional improvement was moderate. The mean follow-up after the
      expandable prosthesis implantation was 6 years (range, 6 months to 10 years) and
      all patients are doing well. CONCLUSIONS: The insertion of an intrathoracic
      prosthesis can dramatically improve the clinical symptoms and reduce the
      functional obstructive syndrome. The expandable prosthesis allowed for
      progressive, well-tolerated recentering of the mediastinum and adjustment for
      growth.

PMID- 11528622
TI  - Natural history of experimental intestinal atresia: morphologic and
      ultrastructural study.
AB  - PURPOSE: The aim of this study was to evaluate a natural history of congenital
      intestinal atresia (IA) in the chick embryo and to assess the type and nature of
      changes in the intestine at various developmental stages. METHODS: Chick embryos
      underwent operative induction of IA on the 12th day of incubation. The procedure
      consisted of electrocoagulation of the mesenteric vessels supplying a 7- to 8-mm
      intestinal segment. The embryos were subjected to macroscopic examination,
      histologic and ultrastructural studies of the preatretic and postatretic bowel
      using the light microscope, scanning, and transmission electron microscopes. All
      investigations were performed in an experimental group (operated embryos), in a
      control group, and in a sham-operated group on the 15th, 17th, 19th, and 21st day
      of incubation. RESULTS: The original technique of an iatrogenic "vascular event"
      proved to be effective because IA developed in 96% of embryos surviving the
      procedure. The affected portion of the bowel underwent progressive necrosis, and
      signs of bowel obstruction could be observed 48 hours after operation. Cord
      atresia (type II) developed in 81% of embryos. Histologic investigations showed
      progressive thinning of mucosa, flattening of mucosal folds, and epithelial
      detachment within the intestine proximal to atresia. There was only mild
      hypertrophy of the muscular layers. All these pathomorphologic changes were of
      rapidly progressive nature until the 17th day of incubation. Later, the rate of
      distension of preatretic bowel and histologic changes were less. Ultrastructural
      investigation of the proximal bowel showed progressive flattening of the
      enterocytes associated with their apical bulging, widening of the intercellular
      spaces, and microvilli atrophy. Surprisingly, at days 19 and 21 of incubation,
      signs of induction of adaptive mechanisms with partial restoration of near-normal
      microvilli pattern were observed. CONCLUSIONS: Study of natural history of
      experimental IA indicates that histologic and ultrastructural lesions of the
      bowel are of dynamic nature and are not only the effect of pathologic
      intraluminal pressure.

PMID- 11528623
TI  - Dicephalus conjoined twins: a historical review with emphasis on viability.
AB  - Dicephalus conjoined twins (2 heads on 1 body) form a distinct subgroup. They are
      often stillborn because of cardiopulmonary malformations. This article describes
      17 historical cases with particular emphasis on viability. There are reliable
      reports of unseparated dicephali reaching maturity; 1 pair (the Tocci brothers)
      reached at least 34 years of age. In the absence of concomitant cardiac,
      pulmonary, and intestinal malformations, dicephalus conjoined twins may well
      attain adulthood. This appears to be unrelated to whether they have 4 (dicephalus
      tetrabrachius) or 3 (dicephalus tribrachius) arms at birth.

PMID- 11528624
TI  - Congenital abdominal aortic aneurysm causing renovascular hypertension,
      cardiomyopathy, and death in a 19-day-old neonate.
AB  - A full-term baby girl who was sent home day of life 2 was admitted to the
      hospital on day of life 7 for respiratory distress and poor feeding. The child
      was found to be hypertensive and in heart failure. Further workup led to the
      diagnosis of a suprarenal abdominal aortic aneurysm, but the infant had
      deteriorated clinically with heart failure, modest renal failure, renovascular
      hypertension, and no operative cure. The child died on day of life 20. Early
      diagnosis and prompt surgical resection are essential to managing this rare and
      lethal condition.

PMID- 11528625
TI  - Ingested needles in a 3-month-old infant.
AB  - This case describes a 3-month-old infant who swallowed multiple straight sewing
      needles that were removed at laparotomy. A motherhood psychiatric disorder was
      suspected.

PMID- 11528626
TI  - Metachronous Epstein-Barr virus-related smooth muscle tumors in a child after
      heart transplantation: case report and review of the literature.
AB  - Soft tissue tumors are uncommon manifestations of Epstein-Barr virus (EBV)
      infection in patients who have had transplants. The authors report 2 metachronous
      EBV-containing smooth muscle tumors in a child who had a heart transplant, and
      review the literature on posttransplant soft tissue tumors.

PMID- 11528627
TI  - Hepatic rupture caused by peliosis hepatis.
AB  - Peliosis hepatis is a rare entity that can affect children and cause fatal
      hepatic hemorrhage or hepatic failure. Radiographic findings are nonspecific and
      can resemble other hepatic pathologies such as cysts, abscesses, metastases, and
      hemangiomatosis. Peliosis hepatis can resolve spontaneously or by withdrawal of
      inciting medications. Certain cases may require surgical resection of the
      involved portions of the liver. Recently, fatal liver hemorrhage was reported in
      2 pediatric patients with a rare congenital muscle disorder known as myotubular
      (centronuclear) myopathy. One of these patients was found at autopsy to have
      peliosis hepatis. The authors report the first successful treatment of life
      threatening liver hemorrhage caused by peliosis hepatis in a child with
      myotubular myopathy. Awareness of this condition may reduce the catastrophic
      complications seen with peliosis hepatis.

PMID- 11528628
TI  - Difficult central venous access: can magnetic resonance angiography help?

PMID- 11528629
TI  - Re: "Glial derived growth factor signaling pathway in infantile hypertrophic
      pyloric stenosis (IHPS)".

PMID- 11528630
TI  - Re: "Gastric volvulus associated with wandering spleen in a child".

PMID- 11528631
TI  - Re: "Management of parapneumonic collections in infants and children".

PMID- 11528633
TI  - Urethral calculi managed with transurethral Holmium laser ablation.
AB  - In situ Holmium laser lithotripsy is a safe, effective procedure for the
      treatment of impacted urethral stones. This procedure can be performed
      transurethrally as an outpatient with minimal tissue trauma and render patients
      stone free. The authors utilized this procedure in 2 patients whose anatomy did
      not allow the calculi to be manipulated into the urinary bladder in a retrograde
      manner. Because of its successful use elsewhere in the urinary tract, we believe
      that Holmium laser lithotripsy may be the treatment of choice for impacted
      urethral stones.

PMID- 11528635
TI  - Unusual duplication of appendix and cecum: extension of the Cave-Wallbridge
      classification.
AB  - Duplicated appendix has, to date, been classified into 3 types. The authors
      present a type of duplicated appendix not previously described. Surgical
      exploration was done in a 14-year-old girl who had an acute abdomen. Surgical
      exploration showed a duplicated appendix that arose from the normal appendix and
      ended in a thick-walled, inflamed, perforated muscular pouch. Duplicated appendix
      is a treatable condition that rarely occurs with colonic duplication and which
      should be considered in the differential diagnosis of lower abdominal pain.

PMID- 11528634
TI  - Thoracoscopic esophagectomy in children.
AB  - Minimal access surgery is an alternative to open surgery in esophageal
      resections. Thoracoscopic surgery has been utilized for both benign and malignant
      esophageal lesions and is a complex and challenging surgical procedure that can
      provide some benefits in comparison with open thoracotomy. Many studies have
      described laparoscopic or thoracoscopic-assisted esophagectomy in adults. So far,
      to the best of our knowledge, there is no study about thoracoscopic esophagectomy
      in children. This report describes 2 pediatric cases of benign esophageal
      lesions: one stricture after accidental ingestion of caustic soda and one
      esophageal stenosis after thyroglossal duct complication. Both patients were
      submitted to thoracoscopic esophagectomy combined with laparotomy and open
      cervical exploration with success. This procedure presents some potential
      advantages when compared with open esophagectomy: shorter hospital stay, precise
      dissection of mediastinal structures, less postoperative pain, less blood loss
      during surgery and less long-term discomfort. In our cases, thoracoscopic surgery
      for children showed the same benefits as in adults. Although very feasible, it
      should not be attempted without sufficient training and should be carried out
      only in specialized medical centers and by surgeons with adequate experience with
      open esophagectomy.

PMID- 11528636
TI  - Pylephlebitis, portal-mesenteric thrombosis, and multiple liver abscesses owing
      to perforated appendicitis.
AB  - The authors report a case of a ruptured retrocecal appendix presenting with
      pylephlebitis, portal-mesenteric thrombosis, and multiple liver abscesses in an 8
      year-old boy. A right hemicolectomy was performed, and liver abscesses were
      drained. The patient was treated with long-term antibiotics and anticoagulation.
      This the only case of perforated appendicitis associated with these 3 morbid
      complications in the modern literature.

PMID- 11528637
TI  - Growth-arrest and inhomogenous echotexture of the affected testis after tumor
      enucleation for unilateral Leydig cell tumor.
AB  - The authors report on an 8-year-old boy with unilateral left-sided Leydig cell
      tumor. After enucleation of the tumor, endocrine disturbances resolved. Long-time
      follow-up for more than 7 years was characterized by growth-arrest of the
      affected gonad and the unchanged appearance of a circumscribed hypoechogenic
      residual lesion within the testis.

PMID- 11528638
TI  - Neonatal diaphragmatic hemangioma.
AB  - The first neonatal case of a hemangioma of the diaphragm in a neonate is
      reported. After 25 months the patient is well with no signs of recurrence.
      Diaphragmatic tumors should be considered in the differential diagnosis of
      neonatal thoracic masses.

PMID- 11528640
TI  - [Lip, cheilitis glandularis].

PMID- 11528639
TI  - [Immunodeficiency, hyper IgE type].

PMID- 11528641
TI  - [Lipodystrophy-coarse facies-acanthosis nigricans, Miescher type].

PMID- 11528642
TI  - [Lipodystrophy, congenital generalized (Berardinelli-Seip syndrome)].

PMID- 11528643
TI  - [Lipodystrophy, familial limb and trunk].

PMID- 11528644
TI  - [Lipogranulomatosis, Farber].

PMID- 11528645
TI  - [Lipomeningocele].

PMID- 11528646
TI  - [Lipoprotein lipase deficiency, familial].

PMID- 11528647
TI  - [Lissencephaly syndrome].

PMID- 11528648
TI  - [Lujan-Fryns syndrome].

PMID- 11528649
TI  - [Lung].

PMID- 11528651
TI  - [Lymphedema].

PMID- 11528650
TI  - [Immunodeficiency, Wiskott-Aldrich type].

PMID- 11528652
TI  - [Machado-Joseph disease].

PMID- 11528653
TI  - [Macroglossia].

PMID- 11528654
TI  - [Macular coloboma-brachydactyly].

PMID- 11528655
TI  - [Mal de Meleda].

PMID- 11528656
TI  - [Malignant hyperthermia].

PMID- 11528658
TI  - [Mandibuloacral dysplasia].

PMID- 11528657
TI  - [Mandible, torus mandibularis].

PMID- 11528659
TI  - [Mandibulofacial dysostosis].

PMID- 11528660
TI  - [Mannosidosis].

PMID- 11528661
TI  - [Maple syrup urine disease].

PMID- 11528662
TI  - [Immunodeficiency with centromeric instability, immunodeficiency-centromeric
      instability-facial anomalies (ICF)].

PMID- 11528663
TI  - [Marden-Walker syndrome].

PMID- 11528664
TI  - [Marfan syndrome].

PMID- 11528665
TI  - [Marinesco-Sjogren syndrome].

PMID- 11528666
TI  - [Marshall-Smith syndrome].

PMID- 11528667
TI  - [Martsolf syndrome].

PMID- 11528669
TI  - [Maxillofacial dysostosis].

PMID- 11528668
TI  - [Maxilla, median alveolar cleft].

PMID- 11528670
TI  - [Maxillonasal dysplasia, Binder type].

PMID- 11528671
TI  - [McDonough syndrome].

PMID- 11528672
TI  - [Meckel diverticulum].

PMID- 11528673
TI  - [Meckel syndrome].

PMID- 11528674
TI  - [Megacystis-megaduodenum syndrome].

PMID- 11528675
TI  - [Megacystis-microcolon-intestinal hypoperistalsis syndrome].

PMID- 11528676
TI  - [Incontinentia pigmenti, Bloch-Sulzberger syndrome].

PMID- 11528677
TI  - [Megalencephaly].

PMID- 11528678
TI  - [Megalocornea-mental retardation syndrome].

PMID- 11528679
TI  - [Meier-Gorlin syndrome (ear-patella-short stature syndrome)].

PMID- 11528680
TI  - [Melorheostosis].

PMID- 11528681
TI  - [Meningocele].

PMID- 11528683
TI  - [Meningomyelocele].

PMID- 11528682
TI  - [Meningocele-conotruncal heart defect, Korsakoff's type].

PMID- 11528684
TI  - [Menkes disease].

PMID- 11528685
TI  - [Mental retardation-heart defects-blepharophimosis].

PMID- 11528686
TI  - [Mesomelic dysplasia].

PMID- 11528687
TI  - [Metachromatic leukodystrophy].

PMID- 11528688
TI  - [Inflammatory disease, neonatal Bates-Lorber type].

PMID- 11528690
TI  - [Metatropic dysplasia].

PMID- 11528689
TI  - [Metaphyseal chondrodysplasia (metaphyseal dysplasia)].

PMID- 11528691
TI  - [Methylenetetrahydrofolate reductase deficiency].

PMID- 11528692
TI  - [Michelin tire baby syndrome].

PMID- 11528693
TI  - [Michels syndrome].

PMID- 11528694
TI  - [IVIC syndrome].

PMID- 11528695
TI  - [Microcephalic osteodysplastic primordial dwarfism].

PMID- 11528696
TI  - [Microcephaly-hiatus hernia-nephrosis, Galloway type].

PMID- 11528697
TI  - [Microcephaly with chorioretinopathy].

PMID- 11528698
TI  - [Microphthalmia with linear skin defects (MLS) syndrome].

PMID- 11528699
TI  - [Microvillus inclusion disease].

PMID- 11528700
TI  - [Mietens-Weber syndrome].

PMID- 11528701
TI  - [Mitochondrial encephalomyopathy].

PMID- 11528702
TI  - [MODED syndrome].

PMID- 11528704
TI  - [Jaw-winking syndrome].

PMID- 11528705
TI  - [Mucopolysaccharidosis (I-VII)].

PMID- 11528703
TI  - [Mosaic variegated aneuploidy].

PMID- 11528706
TI  - [Mullerian duct].

PMID- 11528707
TI  - [Multiple midline defects].

PMID- 11528708
TI  - [Mulvihill-Smith syndrome].

PMID- 11528709
TI  - [Jejunal atresia].

PMID- 11528710
TI  - [MURCS association].

PMID- 11528711
TI  - [Muscular atrophy, spinal and bulbar (SBMA), X-linked Kennedy type].

PMID- 11528712
TI  - [Muscular dystrophy, congenital with mental retardation, Fukuyama type].

PMID- 11528713
TI  - [Muscular dystrophy, Duchenne type, Becker type].

PMID- 11528714
TI  - [Muscular dystrophy, facio-scapulo-humeral].

PMID- 11528715
TI  - [Muscular dystrophy, limb-girdle].

PMID- 11528716
TI  - [Muscular dystrophy, oculopharyngeal].

PMID- 11528717
TI  - [Mutchinick syndrome].

PMID- 11528718
TI  - [Johanson-Blizzard syndrome].

PMID- 11528719
TI  - [Myasthenic syndrome, congenital slow channel type].

PMID- 11528720
TI  - [Myasthenic syndrome, familial infantile type].

PMID- 11528721
TI  - [Myopathy, central core disease type].

PMID- 11528722
TI  - [Myopathy, congenital fiber type disproportion].

PMID- 11528723
TI  - [Myopathy, hereditary with lactic acidosis].

PMID- 11528724
TI  - [Myopathy, myotubular].

PMID- 11528725
TI  - [Myopathy, nemaline].

PMID- 11528726
TI  - [Myopathy, ocular with hypogonadism].

PMID- 11528727
TI  - [Myopathy, reducing body].

PMID- 11528728
TI  - [Myotonia congenita].

PMID- 11528729
TI  - [Joubert syndrome].

PMID- 11528730
TI  - [Myotonic dystrophy].

PMID- 11528731
TI  - [Myxoma, intracardiac].

PMID- 11528732
TI  - [Nail-patella syndrome].

PMID- 11528733
TI  - [Nails].

PMID- 11528734
TI  - [Naso-digital-acoustic syndrome, Keipert type].

PMID- 11528735
TI  - [Nasopalpebral lipoma-coloboma syndrome].

PMID- 11528736
TI  - [Nasopharyngeal cyst].

PMID- 11528737
TI  - [Neck branchial cleft fistula, cystic hygroma of the neck].

PMID- 11528738
TI  - [Neonatal Marfan syndrome].

PMID- 11528739
TI  - [Nephritis-deafness(sensorineural), hereditary type].

PMID- 11528740
TI  - [Kabuki make-up syndrome].

PMID- 11528741
TI  - [Nephrosis].

PMID- 11528742
TI  - [Neu-Laxova syndrome].

PMID- 11528743
TI  - [Neuroaxonal dystrophy, infantile].

PMID- 11528744
TI  - [Neurocutaneous melanosis].

PMID- 11528745
TI  - [Neuroectodermal melanolysosomal syndrome].

PMID- 11528746
TI  - [Neuroectodermal syndrome, Flynn-Aird type (Flynn-Aird syndrome)].

PMID- 11528747
TI  - [Neuro-facio-digito-renal syndrome].

PMID- 11528748
TI  - [Neurofibromatosis (von Recklinghausen disease)].

PMID- 11528749
TI  - [Neuronal ceroid-lipofuscinosis].

PMID- 11528750
TI  - [Kallmann syndrome].

PMID- 11528751
TI  - [Neuropathy, congenital motor & sensory-skeletal-laryngeal defects].

PMID- 11528753
TI  - [Neuropathy, hereditary motor and sensory type I, II, hereditary with pressure
      palsies].

PMID- 11528752
TI  - [Neuropathy, giant axonal].

PMID- 11528754
TI  - [Neuropathy, hereditary recurrent brachial].

PMID- 11528755
TI  - [Nevi-atrial myxoma-myxoid neurofibromas-ephelides (Carney complex)].

PMID- 11528756
TI  - [Nevoid basal cell carcinoma syndrome].

PMID- 11528757
TI  - [Nevo syndrome].

PMID- 11528758
TI  - [Nevus].

PMID- 11528759
TI  - [Niemann-Pick disease (A, B, C)].

PMID- 11528760
TI  - [Night blindness, congenital].

PMID- 11528761
TI  - [Nijmegen breakage syndrome].

PMID- 11528762
TI  - [Noonan syndrome].

PMID- 11528763
TI  - [Norrie disease].

PMID- 11528764
TI  - [Nose].

PMID- 11528765
TI  - [Karsch-Neugebauer syndrome].

PMID- 11528766
TI  - [Ocular dermoids].

PMID- 11528767
TI  - [Ocular drusen].

PMID- 11528768
TI  - [Ocular motor apraxia, Cogan congenital type].

PMID- 11528769
TI  - [Oculo-auriculo-vertebral spectrum].

PMID- 11528770
TI  - [Oculo-cerebro-cutaneous syndrome].

PMID- 11528771
TI  - [Oculo-cerebro-facial syndrome, Kaufman type].

PMID- 11528772
TI  - [KBG syndrome].

PMID- 11528773
TI  - [Oculo-cerebro-renal syndrome of Lowe (OCRL)].

PMID- 11528774
TI  - [Oculo-dento-osseous syndrome].

PMID- 11528775
TI  - [Oculo-ectodermal syndrome].

PMID- 11528776
TI  - [Oculo-encephalo-hepato-renal syndrome].

PMID- 11528777
TI  - [Oculo-facial syndrome, Bencze type].

PMID- 11528778
TI  - [Oculo-facio-cardio-dental syndrome].

PMID- 11528779
TI  - [Oculo-mandibulo-facial syndrome. Hallermann-Streiff syndrome].

PMID- 11528780
TI  - [Oculo-osteo-cutaneous syndrome, Toumaala-Haapanen type].

PMID- 11528781
TI  - [Oculo-reno-cerebellar syndrome].

PMID- 11528782
TI  - [Odonto-onychodermal dysplasia].

PMID- 11528783
TI  - [Keratosis palmaris et plantaris of Unna-Thost].

PMID- 11528784
TI  - [Odonto-onychodysplasia-alopecia].

PMID- 11528785
TI  - [Odonto-trichomelic syndrome].

PMID- 11528786
TI  - [Olivopontocerebellar atrophy].

PMID- 11528787
TI  - [Omodysplasia].

PMID- 11528788
TI  - [Omphalocele].

PMID- 11528789
TI  - [Omphalomesenteric duct anomalies].

PMID- 11528790
TI  - [Onychodystrophy-coniform teeth-sensorineural hearing loss].

PMID- 11528791
TI  - [Onycho-trichodysplasia-neutropenia].

PMID- 11528792
TI  - [Ophthalmo-mandibulo-melic dwarfism].

PMID- 11528793
TI  - [Ophthalmoplegia].

PMID- 11528794
TI  - [Keutel syndrome].

PMID- 11528795
TI  - [Opsismodysplasia].

PMID- 11528796
TI  - [Optic atrophy, Behr syndrome].

PMID- 11528797
TI  - [Optic disk].

PMID- 11528798
TI  - [Optic nerve hypoplasia].

PMID- 11528800
TI  - [Oral dermoids].

PMID- 11528799
TI  - [Optico-cochleo-dentate-degeneration].

PMID- 11528801
TI  - [Oral-facial-skeletal syndrome].

PMID- 11528802
TI  - [Ornithine transcarbamylase deficiency].

PMID- 11528803
TI  - [Oro-cranio-digital syndrome].

PMID- 11528805
TI  - [Oro-facio-digital syndrome].

PMID- 11528804
TI  - [Kidney, medullary sponge].

PMID- 11528806
TI  - [Osteochondrodysplasia with hypertrichosis].

PMID- 11528807
TI  - [Osteodysplasia, lipomembranous polycystic-dementia].

PMID- 11528808
TI  - [Osteodysplastica gerodermia, Bamatter type].

PMID- 11528809
TI  - [Osteodysplasty].

PMID- 11528810
TI  - [Osteodystrophy-mental retardation, Ruvalcaba type].

PMID- 11528811
TI  - [Osteoectasia].

PMID- 11528812
TI  - [Osteofibrous dysplasia of tibia and fibula].

PMID- 11528813
TI  - [Osteogenesis imperfecta].

PMID- 11528814
TI  - [Kidney, polycystic disease-cataract-blindness].

PMID- 11528815
TI  - [Osteoglophonic dysplasia].

PMID- 11528816
TI  - [Osteolysis].

PMID- 11528817
TI  - [Osteomesopyknosis].

PMID- 11528818
TI  - [Osteopathia striata].

PMID- 11528819
TI  - [Osteopathia striata-cranial sclerosis-megalencephaly].

PMID- 11528820
TI  - [Kidney, polycystic disease, dominant].

PMID- 11528822
TI  - [Osteopoikilosis].

PMID- 11528821
TI  - [Osteopetrosis, benign dominant].

PMID- 11528823
TI  - [Osteoporosis, juvenile idiopathic].

PMID- 11528824
TI  - [Osteoporosis-pseudoglioma syndrome].

PMID- 11528825
TI  - [Oto-dental dysplasia].

PMID- 11528826
TI  - [Oto-oculo-musculo-skeletal syndrome].

PMID- 11528827
TI  - [Oto-onycho-peroneal syndrome].

PMID- 11528828
TI  - [Oto-palato-digital syndrome, type I].

PMID- 11528829
TI  - [Oto-palato-digital syndrome, type II].

PMID- 11528830
TI  - [Otosclerosis].

PMID- 11528831
TI  - [Kidney, renal dysplasia, Potter type II].

PMID- 11528832
TI  - [Oto-spondylo-megaepiphyseal dysplasia].

PMID- 11528833
TI  - [Overgrowth, macrocephaly-hemangioma, Riley-Smith type].

PMID- 11528834
TI  - [Overgrowth-renal hamartoma, Perlman type].

PMID- 11528835
TI  - [Pachydermoperiostosis].

PMID- 11528836
TI  - [Pachyonychia congenita-steatocystoma multiplex].

PMID- 11528837
TI  - [Pacman dysplasia].

PMID- 11528838
TI  - [Palatopharyngeal incompetence].

PMID- 11528839
TI  - [Pallister-Killian mosaic syndrome].

PMID- 11528840
TI  - [Pallister-W syndrome].

PMID- 11528841
TI  - [Palsy, congenital facial].

PMID- 11528842
TI  - [Palsy, progressive bulbar of childhood].

PMID- 11528843
TI  - [Pancytopenia, Fanconi type].

PMID- 11528844
TI  - [King syndrome].

PMID- 11528845
TI  - [Papillomavirus, congenital infection].

PMID- 11528846
TI  - [Paralysis, hyperkalemic periodic].

PMID- 11528847
TI  - [Paramyotonia congenita].

PMID- 11528848
TI  - [Paraplegia, familial spastic].

PMID- 11528849
TI  - [Parastremmatic dysplasia].

PMID- 11528850
TI  - [Pseudohypoparathyroidism].

PMID- 11528851
TI  - [Parietal foramina-clavicular hypoplasia].

PMID- 11528852
TI  - [Parotitis, punctate].

PMID- 11528853
TI  - [Pectus carinatum, excavatum].

PMID- 11528854
TI  - [Pelizaeus-Merzbacher disease].

PMID- 11528856
TI  - [Klippel-Feil syndrome].

PMID- 11528855
TI  - [Pemphigus, benign familial].

PMID- 11528857
TI  - [Pena-Shokeir syndrome].

PMID- 11528858
TI  - [Penoscrotal transposition].

PMID- 11528859
TI  - [Pentalogy of Cantrell].

PMID- 11528860
TI  - [Perrault syndrome].

PMID- 11528861
TI  - [Ichthyosis].

PMID- 11528862
TI  - [Pharynx/larynx hypoplasia-omphalocele, Shprintzen-Goldberg type].

PMID- 11528863
TI  - [Phenylketonuria].

PMID- 11528864
TI  - [Pilo-dento-ungular dysplasia with microcephaly].

PMID- 11528866
TI  - [Poikiloderma, hereditary acrokeratotic, Kindler-Weary type].

PMID- 11528865
TI  - [Plagiocephaly].

PMID- 11528867
TI  - [Kniest dysplasia].

PMID- 11528868
TI  - [Poikiloderma, sclerosing, hereditary].

PMID- 11528869
TI  - [Poland syndrome].

PMID- 11528870
TI  - [Polyposis-alopecia-pigmentation-nail defects, Cronkhite-Canada syndrome].

PMID- 11528871
TI  - [Polysyndactyly].

PMID- 11528872
TI  - [Polysyndactyly-cardiac malformations].

PMID- 11528873
TI  - [Polysyndactyly-dysmorphic craniofacies, Greig type].

PMID- 11528874
TI  - [Porphyria].

PMID- 11528875
TI  - [Prader-Willi syndrome].

PMID- 11528876
TI  - [Knobloch syndrome].

PMID- 11528877
TI  - [Progeria].

PMID- 11528878
TI  - [Progeria, neonatal Rautenstrauch-Wiedemann type].

PMID- 11528879
TI  - [Progeroid syndrome with Ehlers-Danlos features].

PMID- 11528880
TI  - [Proteus syndrome].

PMID- 11528881
TI  - [Prune-belly syndrome].

PMID- 11528882
TI  - [Pseudoachondroplastic dysplasia].

PMID- 11528884
TI  - [Pseudo-trisomy 13 syndrome].

PMID- 11528883
TI  - [Pseudoaminopterin syndrome].

PMID- 11528885
TI  - [Pterygia-dysmorphic facies-short stature-mental retardation].

PMID- 11528886
TI  - [Pterygium syndrome, multiple, multiple lethal].

PMID- 11528887
TI  - [Pterygium syndrome, popliteal].

PMID- 11528888
TI  - [Knuckle pads-leukonychia-deafness].

PMID- 11528889
TI  - [Pyknodysostosis].

PMID- 11528890
TI  - [Pyle disease].

PMID- 11528891
TI  - [Pyloric stenosis].

PMID- 11528892
TI  - [Pyloroduodenal atresia, hereditary].

PMID- 11528893
TI  - [Pyruvate dehydrogenase complex deficiency].

PMID- 11528894
TI  - [Krabbe disease, globoid cell leukodystrophy].

PMID- 11528895
TI  - [Radial defects].

PMID- 11528896
TI  - [Radial hypoplasia-triphalangeal thumbs-hypospadias-diastema].

PMID- 11528897
TI  - [Radial-renal-ocular syndrome].

PMID- 11528898
TI  - [Radial-renal syndrome].

PMID- 11528899
TI  - [Radial-ulnar synostosis].

PMID- 11528901
TI  - [Raine syndrome].

PMID- 11528900
TI  - [RAG syndrome].

PMID- 11528902
TI  - [Refsum disease].

PMID- 11528903
TI  - [Renal agenesis, bilateral].

PMID- 11528904
TI  - [Winter syndrome].

PMID- 11528905
TI  - [Retinitis pigmentosa].

PMID- 11528906
TI  - [Retinoblastoma].

PMID- 11528907
TI  - [Rett syndrome].

PMID- 11528908
TI  - [Rhizomelic syndrome, Urbach type].

PMID- 11528909
TI  - [Rieger syndrome].

PMID- 11528910
TI  - [Ritscher-Schinzel syndrome].

PMID- 11528911
TI  - [Roberts syndrome].

PMID- 11528912
TI  - [Krause-Kivlin syndrome(Krause-Van Schooneveld-Kivlin syndrome, Peters-plus
      syndrome)].

PMID- 11528913
TI  - [Robinow syndrome].

PMID- 11528914
TI  - [Rothmund-Thomson syndrome].

PMID- 11528915
TI  - [Rubinstein-Taybi broad thumb-hallux syndrome].

PMID- 11528917
TI  - [Satoyoshi syndrome].

PMID- 11528916
TI  - [Sacrococcygeal dysgenesis syndrome].

PMID- 11528918
TI  - [Say-Meyer syndrome].

PMID- 11528919
TI  - [Scalp defects-postaxial polydactyly].

PMID- 11528920
TI  - [Scalp-ear-nipple syndrome].

PMID- 11528921
TI  - [Schindler-disease/Kanzaki disease].

PMID- 11528922
TI  - [Kuskokwim syndrome].

PMID- 11528923
TI  - [Schinzel-Giedion syndrome].

PMID- 11528924
TI  - [Scimitar syndrome].

PMID- 11528925
TI  - [Scleroderma, familial progressive].

PMID- 11528926
TI  - [Sclerosteosis].

PMID- 11528928
TI  - [Kyphomelic dysplasia].

PMID- 11528927
TI  - [Seckel syndrome].

PMID- 11528929
TI  - [Seizures, febrile].

PMID- 11528930
TI  - [Seizures-ichthyosis-mental retardation].

PMID- 11528931
TI  - [Seizures, progressive myoclonic].

PMID- 11528932
TI  - [Septo-optic dysplasia].

PMID- 11528933
TI  - [Short rib-polydactyly syndrome, types I, II, III, IV].

PMID- 11528935
TI  - [Shwachman syndrome].

PMID- 11528934
TI  - [SHORT syndrome].

PMID- 11528936
TI  - [Sialidosis].

PMID- 11528937
TI  - [Silver-Russell syndrome].

PMID- 11528938
TI  - [Simpson-Golabi-Behmel syndrome].

PMID- 11528939
TI  - [Lacrimal glands].

PMID- 11528940
TI  - [Singleton-Merten syndrome].

PMID- 11528941
TI  - [Sirenomelia sequence].

PMID- 11528942
TI  - [Situs inversus viscerum].

PMID- 11528943
TI  - [Sjogren-Larsson syndrome].

PMID- 11528944
TI  - [Skeletal bowing-cortical thickening-bone fragility-ichthyosis].

PMID- 11528945
TI  - [Skeletal dysplasia, 3-M type].

PMID- 11528946
TI  - [Lacrimo-auriculo-dento-digital syndrome].

PMID- 11528947
TI  - [Skeletal dysplasia, boomerang dysplasia].

PMID- 11528948
TI  - [Skeletal dysplasia, de la Chapelle type].

PMID- 11528949
TI  - [Skeletal dysplasia, Fuhrmann type].

PMID- 11528950
TI  - [Skeletal dysplasia, Schneckenbecken type].

PMID- 11528952
TI  - [Skin].

PMID- 11528951
TI  - [Skeletal dysplasia, Weismann-Netter, Stuhl type].

PMID- 11528953
TI  - [Small patella syndrome].

PMID- 11528955
TI  - [Smith-Lemli-Opitz syndrome].

PMID- 11528954
TI  - [Smith-Fineman-Myers syndrome].

PMID- 11528956
TI  - [Larsen syndrome].

PMID- 11528957
TI  - [Spherophakia-brachymorphia syndrome].

PMID- 11528958
TI  - [Spinal muscular atrophy].

PMID- 11528959
TI  - [Spinocerebellar degeneration-corneal dystrophy].

PMID- 11528960
TI  - [SPONASTRIME dysplasia].

PMID- 11528961
TI  - [Spondylocarpotarsal synostosis syndrome].

PMID- 11528962
TI  - [Jarcho-Levin syndrome].

PMID- 11528963
TI  - [Spondyloenchondroplasia].

PMID- 11528964
TI  - [Spondyloepi (meta) physeal dysplasia-other forms].

PMID- 11528965
TI  - [Spondyloepimetaphyseal dysplasia-joint laxity].

PMID- 11528966
TI  - [Spondyloepiphyseal dysplasia congenita].

PMID- 11528967
TI  - [Larynx].

PMID- 11528968
TI  - [Spondyloepiphyseal dysplasia tarda].

PMID- 11528969
TI  - [Spondylometaphyseal dysplasia, Kozlowski type].

PMID- 11528970
TI  - [Spondyloperipheral dysplasia].

PMID- 11528971
TI  - [Stratton-Parker syndrome].

PMID- 11528972
TI  - [Sturge-Weber syndrome].

PMID- 11528973
TI  - [Stuve-Wiedemann syndrome].

PMID- 11528974
TI  - [Ichthyosis-cheek-eyebrow syndrome].

PMID- 11528975
TI  - [Succinyl-CoA: 3-ketoacid CoA transferase deficiency].

PMID- 11528976
TI  - [Symphalangism].

PMID- 11528977
TI  - [Syndactyly].

PMID- 11528978
TI  - [Syndactyly-microcephaly-mental retardation, Filippi type].

PMID- 11528980
TI  - [Teeth, dentinogenesis imperfecta].

PMID- 11528979
TI  - [Teeth, amelogenesis imperfecta].

PMID- 11528981
TI  - [Teeth, impacted].

PMID- 11528982
TI  - [Telangiectasia, Osler hemorrhagic].

PMID- 11528983
TI  - [Ter Haar syndrome].

PMID- 11528984
TI  - [Teratoma, presacral-sacral dysgenesis].

PMID- 11528985
TI  - [Teratoma, sacrococcygeal].

PMID- 11528986
TI  - [Thanatophoric dysplasia].

PMID- 11528987
TI  - [Thomas syndrome].

PMID- 11528988
TI  - [Thoracic dysplasia-hydrocephalus syndrome].

PMID- 11528989
TI  - [Thoracopelvic dysostosis, thoracolaryngopelvic dysplasia, Barnes syndrome].

PMID- 11528990
TI  - [Thrombocytopenia-absent radius, TAR syndrome].

PMID- 11528991
TI  - [Thumb, triphalangeal].

PMID- 11528992
TI  - [Tibial aplasia/hypoplasia].

PMID- 11528993
TI  - [Gollop-Wolfgang syndrome].

PMID- 11528994
TI  - [Tonoki syndrome].

PMID- 11528995
TI  - [Torg osteolysis syndrome].

PMID- 11528996
TI  - [Toriello-Carey syndrome].

PMID- 11528997
TI  - [Toriello syndrome].

PMID- 11528998
TI  - [Laurence-Moon syndrome].

PMID- 11528999
TI  - [Tourette syndrome].

PMID- 11529000
TI  - [Tracheoesophageal fistula/congenital esophageal atresia].

PMID- 11529001
TI  - [Tricho-dento-osseous syndrome].

PMID- 11529002
TI  - [Trichodermodysplasia-dental defects or alterations].

PMID- 11529003
TI  - [Tricho-hepato-enteric syndrome].

PMID- 11529004
TI  - [Lens].

PMID- 11529005
TI  - [Tricho-odonto-onychial dysplasia].

PMID- 11529006
TI  - [Trichoonychodysplasia-xeroderma].

PMID- 11529007
TI  - [Tricho-rhino-phalangeal syndrome, type I].

PMID- 11529008
TI  - [Tricho-rhino-phalangeal syndrome, type II].

PMID- 11529009
TI  - [Tricho-rhino-phalangeal syndrome, type III].

PMID- 11529010
TI  - [Trichothiodystrophy].

PMID- 11529011
TI  - [Tuberous sclerosis].

PMID- 11529012
TI  - [Tubular stenosis].

PMID- 11529013
TI  - [Turcot syndrome].

PMID- 11529014
TI  - [Turner syndrome].

PMID- 11529015
TI  - [Lentigines syndrome, multiple].

PMID- 11529017
TI  - [Tyrosinemia].

PMID- 11529016
TI  - [Twins, conjoined].

PMID- 11529018
TI  - [Umbilical cord].

PMID- 11529019
TI  - [Uniparental disomy (UPD) chromosome 14].

PMID- 11529020
TI  - [Uniparental disomy (UPD) chromosome 16].

PMID- 11529021
TI  - [Urofacial syndrome].

PMID- 11529022
TI  - [Usher syndrome].

PMID- 11529023
TI  - [VATER association].

PMID- 11529024
TI  - [Velo-cardio-facial syndrome].

PMID- 11529025
TI  - [Lenz microphthalmia syndrome].

PMID- 11529026
TI  - [Vesico-ureteral reflux].

PMID- 11529027
TI  - [Vitamin B6 dependency].

PMID- 11529028
TI  - [Vitamin D dependency].

PMID- 11529029
TI  - [von Hippel-Lindau syndrome].

PMID- 11529030
TI  - [Ichthyosis-coloboma-heart defect-deafness-mental retardation].

PMID- 11529031
TI  - [Waardenburg syndromes].

PMID- 11529032
TI  - [Walker-Warburg syndrome].

PMID- 11529033
TI  - [Weaver syndrome(Weaver-Smith syndrome)].

PMID- 11529034
TI  - [Werner syndrome].

PMID- 11529035
TI  - [Leprechaunism].

PMID- 11529036
TI  - [Williams syndrome].

PMID- 11529037
TI  - [Wilms tumor-pseudohermaphroditism-glomerulopathy, Denys-Drash type].

PMID- 11529038
TI  - [Wilson disease].

PMID- 11529039
TI  - [Winchester syndrome].

PMID- 11529040
TI  - [Wolman disease].

PMID- 11529041
TI  - [Wrinkly skin syndrome].

PMID- 11529042
TI  - [WT syndrome].

PMID- 11529043
TI  - [X-linked alpha-thalassemia/mental retardation (ATR-X) syndrome].

PMID- 11529044
TI  - [X-linked mental retardation].

PMID- 11529045
TI  - [Leri pleonosteosis syndrome].

PMID- 11529046
TI  - [X-linked mental retardation, fragile X syndrome].

PMID- 11529047
TI  - [Xanthomatosis, cerebrotendinous].

PMID- 11529048
TI  - [Xeroderma pigmentosum].

PMID- 11529049
TI  - [Young-Simpson syndrome].

PMID- 11529050
TI  - [Yunis-Varon syndrome].

PMID- 11529051
TI  - [Lesch-Nyhan syndrome].

PMID- 11529052
TI  - [Zellweger syndrome].

PMID- 11529053
TI  - [Epidemiological aspects of birth defects].

PMID- 11529054
TI  - [Comprehensive medical care].

PMID- 11529055
TI  - [Genetic counseling].

PMID- 11529056
TI  - [Birth defects monitoring].

PMID- 11529057
TI  - [Liddle syndrome].

PMID- 11529058
TI  - [Limb and scalp defects, Adams-Oliver type].

PMID- 11529059
TI  - [IFAP syndrome(ichthyosis follicularis, alopecia, and photophobia syndrome)].

PMID- 11529060
TI  - [Limb body wall complex].

PMID- 11529061
TI  - [Limb defect with absent ulna/fibula].

PMID- 11529062
TI  - [Limb-oto-cardiac syndrome].

PMID- 11529063
TI  - [Limb reduction-ichthyosis, CHILD syndrome].

PMID- 11529064
TI  - [Limb, upper hypoplasia-mullerian duct defects].

PMID- 11529065
TI  - [Limbs, supernumerary].

PMID- 11529066
TI  - Relevance of reactivity determinants to exposure assessment and biological
      monitoring of the elements.

PMID- 11529067
TI  - Increasing utilisation efficiency of ferric chloride etchant in industrial
      photochemical machining.
AB  - The environmental effects of photochemical machining (PCM) can be appreciable in
      view of the nature of the industry whereby various chemicals are used in the
      preparation and cleaning of metal surfaces, photographic processing of
      phototooling, coating and selective removal (development) of photoresists,
      etching through apertures in the resist stencils and stripping of resist after
      etching. This paper concerns the environmental impact of ferric chloride, the
      most commonly used etchant in PCM, and is believed to be the first quantitative
      analysis for the PCM industry. The findings showed that more than half of the PCM
      companies used regeneration of ferric chloride etchant and 76.3% of companies
      were prepared to use a more environment-friendly regeneration system at a higher
      overall cost. Regarding ferric chloride consumption, it was found that the
      performance of companies varies greatly: companies using regeneration were, on
      average, nearly seven times (340.8% compared with 51.1%) more efficient than
      those that do not regenerate, and the most efficient company used 135 times less
      etchant than the least efficient company. The findings of this study and the
      analysis carried out can be used by PCM companies as a benchmark in assessing
      their environmental performance with respect to etchant consumption efficiency.

PMID- 11529068
TI  - Characterisation of a Hg(II) ion optrode based on Nafion-1-(2-thiazolylazo)-2
      naphthol composite thin films.
AB  - An optrode for Hg2+ ions based on a Nafion-1-(2-thiazolylazo)-2-naphtol (TAN)
      composite thin film has been developed. This optrode has a wide linear response
      range of 1-75 microM (pH 6) of Hg2+ ions with a limit of detection of 0.05 microM
      (10 micrograms l-1), which is sufficiently adequate for many environmental
      monitoring applications. The reflectance signal response shows a close
      correlation with the theoretical model derived. The response time of the optrode
      thin film was within 5-7 min to reach 95% of the final signal, depending on the
      concentration of Hg2+ ions. The selectivity of optrode to Hg2+ ions in phosphate
      buffer is good, with Co2+ and Ni2+ ions as the main interferences.

PMID- 11529069
TI  - Clean air takes to the Web.

PMID- 11529070
TI  - Environmental use of diffusive samplers: evaluation of reliable diffusive uptake
      rates for benzene, toluene and xylene.

PMID- 11529071
TI  - Canada and US focus on hormone disrupters.

PMID- 11529072
TI  - Characterisation of workers' exposure in a Russian nickel refinery.
AB  - In support of a feasibility study of reproductive and developmental health among
      females employed in the Monchegorsk (Russia) nickel refinery, personal exposure
      and biological monitoring assessments were conducted. The inhalable aerosol
      fraction was measured and characterised by chemical speciation and particle-size
      distribution measurements. Unexpected findings were that: (i), pyrometallurgical
      working environments had significant levels of water-soluble nickel; (ii),
      significant exposure to cobalt occurred for the nickel workers; (iii), particles
      of size corresponding to the thoracic and respirable fractions appeared to be
      virtually absent in most of the areas surveyed. The water-soluble fraction is
      judged to be primarily responsible for the observed urinary nickel and cobalt
      concentrations. It is concluded relative to current international occupational
      exposure limits for nickel in air, and because of the high nickel concentrations
      observed in urine, that the Monchegorsk nickel workers are heavily exposed. The
      implication of this finding for follow-up epidemiological work is alluded to.

PMID- 11529073
TI  - CEN air quality standards.

PMID- 11529074
TI  - Sampling: the uncertainty that dares not speak its name.

PMID- 11529075
TI  - Development of an international standard for the determination of metals and
      metalloids in workplace air using ICP-AES: evaluation of sample dissolution
      procedures through an interlaboratory trial.
AB  - Inductively coupled plasma atomic emission spectrometry (ICP-AES) is rapidly
      overtaking atomic absorption spectrometry (AAS) as the method of choice for the
      determination of toxic metals in workplace air. However, the few ICP-AES methods
      that have been published are not well characterised in terms of the effectiveness
      of the sample dissolution procedures described and their validation status. The
      International Standards Organization (ISO) is currently engaged in developing ISO
      15202, which will describe a generic method for the determination of metals and
      metalloids in airborne particulate matter by ICP-AES. One part of the proposed
      standard deals with dissolution procedures. The ISO work has been supported by a
      project carried out in the authors' laboratory to identify, develop and validate
      sample dissolution procedures for inclusion in the proposed standard. This paper
      describes an interlaboratory comparison carried out to assess the performance of
      selected procedures using samples of airborne particulate matter collected on
      filters with a multiport sampler. Five dissolution procedures were tested. These
      included an ultrasonic agitation procedure, two hot-plate procedures (based upon
      NIOSH 7300 and OSHA ID 125G) and two microwave-assisted procedures (based upon
      EPA 3052). It was shown that the dissolution procedures selected for use in the
      trial and used internally at HSL generally gave equivalent performance. As
      expected, a wider spread of results was obtained by participants in the trial.
      More specifically, there exists some reservation regarding the ability of the
      ultrasonic and hot-plate procedures to attack fully on a consistent basis some
      resistant materials, e.g., chromium containing particulate matter. Above all, the
      trial demonstrated the usefulness of microwave-assisted dissolution procedures in
      a modern laboratory.

PMID- 11529076
TI  - Determination of Ni(CO)4, Fe(CO)5, Mo(CO)6, and W(CO)6 in sewage gas by using
      cryotrapping gas chromatography inductively coupled plasma mass spectrometry.
AB  - Evidence for the occurrence of Ni(CO)4 in addition to Mo(CO)6 and W(CO)6 in
      fermentation gases from a municipal sewage treatment plant is presented for the
      first time. The gases were sampled at the top of the sewage sludge digester using
      Tedlar bags, and were analysed using cryotrapping followed by gas chromatography
      coupled with inductively coupled mass spectrometry (GC-ICP-MS). The use of an ICP
      MS as an element-specific detector gives sufficiently low detection limits for
      metals and was coupled to a packed column gas chromatograph. This method provides
      information about the speciation of volatile transition metals in contrast to
      previously used methods for the determination of Ni(CO)4 in gas samples. The
      element-specific detection of three different isotopes (m/z 58, 60, 62) and the
      correspondence of the samples' retention times with those of the standard
      provided convincing evidence that Ni(CO)4 is present in the fermentation gas. The
      concentrations found were in the sub-ppb level, which is at least one order of
      magnitude lower than the threshold level of 1 ppb (v/v). In addition, Mo(CO)6 and
      W(CO)6 were also measured in the sub-ppb range in contrast to the absence of
      Fe(CO)5. The stabilities of Ni(CO)4, Fe(CO)5, and Mo(CO)6 were tested in a carbon
      monoxide atmosphere. In the presence of distilled water, the following order of
      stability was found after 11 weeks: Fe(CO)5 < Ni(CO)4 < Mo(CO)6. In the presence
      of an aqueous solution containing nickel, molybdenum, tungsten and iron, however,
      only Fe(CO)5 was significantly decomposed (< 0.3% recovery); Ni(CO)4 and Mo(CO)6
      were stable after 11 weeks. No W(CO)6 was formed. The low stability of Fe(CO)5 in
      the presence of water could be the reason why no volatile iron compound was found
      in sewage gas. This study showed that GC-ICP-MS can be employed to identify
      species-specific traces of metal carbonyls in process gases such as sewage gas.

PMID- 11529077
TI  - A diffusive sampling device for the determination of formaldehyde in air using N
      methyl-4-hydrazino-7-nitrobenzofurazan (MNBDH) as reagent.
AB  - A new method utilizing the diffusive sampling of formaldehyde in air has been
      developed. Formaldehyde is sampled with the use of a glass fiber filter
      impregnated with N-methyl-4-hydrazino-7-nitrobenzofurazan (MNBDH) and phosphoric
      acid. The formaldehyde hydrazone formed is desorbed from the filter with
      acetonitrile and determined by high-performance liquid chromatography (HPLC) with
      UV/visible detection at 474 nm. The sampling rate was determined to be 24.7 mL
      min-1 with a relative standard deviation of 7% for 48 experiments. The measured
      sampling rates were not dependent on the formaldehyde concentration (0.1-1.0 mg m
      3), sampling time (15-482 min) or relative humidity (20-85%). The detection limit
      was 70 micrograms m-3 for a 15 min sampling period and 2 micrograms m-3 for an 8
      h sampling period.

PMID- 11529078
TI  - Evaluation of two adsorbents for diffusive sampling and thermal desorption-gas
      chromatographic analysis of monoterpenes in air.
AB  - Tube type samplers with two different adsorbents, Chromosorb 106 and Tenax TA,
      were evaluated by laboratory experiments and field tests for simultaneous
      diffusive sampling of alpha-pinene, beta-pinene and delta 3-carene and subsequent
      thermal desorption-gas chromatographic analysis. No statistically significant
      effects of exposure time, concentrations of monoterpenes or relative humidity
      were found for samplers with Chromosorb 106 when running a factorial design, with
      the exception of the adsorption of delta 3-carene, for which some weak effects
      were noted. Samplers with Tenax TA were affected by the sampling time as well as
      the concentration for all terpenes, with a strong interaction effect between
      these two factors. The terpenes showed good storage stability on both adsorbents.
      No effect of back-diffusion was noted when using Chromosorb 106, while Tenax TA
      showed some back-diffusion effects. The uptake rates, in ml min-1, for the
      terpenes on Chromosorb 106 were 0.36 for alpha-pinene, 0.36 for beta-pinene and
      0.40 for delta 3-carene. The corresponding average values on Tenax TA were 0.30
      for alpha-pinene, 0.32 for beta-pinene and 0.38 for delta 3-carene. The field
      validation proved that diffusive sampling on Chromosorb 106 agreed well with
      pumped sampling on charcoal for stationary samples, while the personal samples
      indicated a discrepancy of 25% between Chromosorb 106 and charcoal samples. Tenax
      TA generally gave lower results than Chromosorb 106 in all field samples.
      Samplers packed with Chromosorb 106 could be used to monitor terpene levels in
      workplaces such as sawmills. The major advantages with this method are the
      sampling procedure, which is simple to perform compared to other techniques, the
      easily automated analysis procedure and the possibility to reuse the samplers.

PMID- 11529079
TI  - Selection and evaluation of sequential extraction procedures for the
      determination of phosphorus forms in lake sediment.
AB  - In order to achieve comparable measurements in the determination of phosphate
      forms in freshwater sediments, the Standards, Measurements and Testing Programme
      (formerly BCR) of the European Commission has launched a project the first step
      of which was to select and evaluate collaboratively existing extraction
      procedures. This was carried out through expert consultations and a literature
      survey, and was followed by the organisation of a first interlaboratory study for
      the evaluation of four sequential extraction schemes, one of which was selected
      as the most promising method for achieving comparability. This scheme, a modified
      version of the Williams protocol, was further tested in a second interlaboratory
      study. The so-called SMT extraction scheme seems promising and will provide, in
      the near future, a valuable tool for water managers in the field of lake
      restoration. It will be particularly helpful in estimating the stock of P
      potentially available, hence the risk of eutrophication due to internal P
      release.

PMID- 11529080
TI  - Improvement of the BCR three step sequential extraction procedure prior to the
      certification of new sediment and soil reference materials.
AB  - The Standards, Measurements and Testing Programme (formerly BCR) of the European
      Commission proposed a three-step sequential extraction procedure for sediment
      analysis, following extensive expert consultations and two interlaboratory
      studies. This scheme was recently used to certify the extractable trace element
      contents of a sediment reference material (CRM 601). Although this procedure
      offers a means to ensure the comparability of data in this field, some
      difficulties concerning the interlaboratory reproducibility still remain, and a
      new project is currently being conducted to determine the causes of poor
      reproducibility in the extraction scheme. The final objective of the project is
      the certification of new sediment and soil reference materials for their
      extractable contents of Cd, Cr, Cu, Ni, Pb and Zn. This paper presents the
      results of a small-scale interlaboratory study, which aimed to test a revised
      version of the extraction schemes by comparing the original and the modified
      protocols using the CRM 601 sample. This work offers an improvement to the BCR
      sequential extraction procedure through intercomparison exercises. This improved
      procedure will allow the obtaining of CRMs to validate analytical data in the
      analysis of soils and sediments, and it will also facilitate comparability of
      data in the European Union.

PMID- 11529081
TI  - Rising hormones.
AB  - Nineteen-ninety eight was a frantic year in the hormone-disruptor debate, with a
      whole series of studies and initiatives pushing the hormones issue up the policy
      agenda. As policy-makers weigh the options, the environmental monitoring
      community has an important opportunity to shape future policies.

PMID- 11529082
TI  - The extraction of aged polycyclic aromatic hydrocarbon (PAH) residues from a clay
      soil using sonication and a Soxhlet procedure: a comparative study.
AB  - A sonication method was compared with Soxhlet extraction for recovering
      polycyclic aromatic hydrocarbons (PAH) from a clay soil that had been
      contaminated with tar materials for several decades. Using sonication over an 8 h
      extraction period, maximum extraction of the 16 US EPA priority PAH was obtained
      with dichloromethane (DCM)-acetone (1 + 1). The same procedure using hexane
      acetone (1 + 1) recovered 86% of that obtained using DCM-acetone (1 + 1). PAH
      recovery was dependent on time of extraction up to a period of 8 h. The
      sonication procedure showed that individual PAH are extracted at differing rates
      depending on the number of fused rings in the molecule. Soxhlet extraction [with
      DCM-acetone (1 + 1)] over an 8 h period recovered 95% of the PAH removed by the
      sonication procedure using DCM-acetone (1 + 1), indicating that rigorous
      sonication can achieve PAH recoveries similar to those obtained by Soxhlet
      extraction. The lower recovery with the Soxhlet extraction was explained by the
      observed losses of the volatile PAH components after 1-4 h of extraction. The
      type of solvent used, the length of time of extraction and extraction method
      influenced the quantification of PAH in the soil. Therefore, the study has
      implications for PAH analyses in soils and sediments, and particularly for
      contaminated site assessments where the data from commercial laboratories are
      being used. The study emphasizes the importance of establishing (and being
      consistent in the application of) a vigorous extraction, particularly for
      commercial laboratories that handle samples of soil in batches (at different
      times) from a single site investigation or remediation process. The strong
      binding of PAH to soil, forming aged residues, has significant implications for
      extraction efficiency. This paper illustrates the problem of the underestimation
      of PAH using the US EPA method 3550, specifically where a surrogate spike is
      routinely employed and the efficiency of the extraction procedure for aged
      residues is unknown. The implications of this study for environmental monitoring,
      particularly where numerous batches of samples from a single site assessment or
      remediation program are submitted to commercial laboratories, is that it would be
      advisable for these laboratories to check their existing method's extraction
      efficiencies by conducting a time course sonication extraction on their
      particular soil to determine the optimum extraction time.

PMID- 11529083
TI  - Survey of environmental complex systems: pattern recognition of physicochemical
      data describing coastal water quality in the Gulf of Trieste.
AB  - A data set reporting temperature, salinity, dissolved oxygen, nitrogen as
      ammonia, nitrite and nitrate, silicate, chlorophyll a and phaeopigment values,
      determined in seawaters sampled during two years with a monthly frequency in 16
      stations in the Gulf of Trieste, and at different depths of the water column, has
      been studied. In order to find synthetic descriptors useful for following the
      spatial and temporal variations of biogeochemical phenomena occurring in the
      considered ecosystem, the data set has been factorized using principal component
      analysis. A graphical display of scores, by means of boxplots and biplots, helped
      in the interpretation of the data set. The first factor conditioning the system
      is related to the input of freshwater from the estuary of the Isonzo River and to
      the stratification of the seawater (thermohaline discontinuity), while the second
      and third components describe interactions between biological activity, nutrients
      and physicochemical parameters; typical spring and autumn phytoplankton blooms
      were identified, in addition to an exceptional winter bloom conditioned by
      anomalous meteorological/climatic conditions. The fourth principal component
      explains the reducing activity of seawaters, which often increases when the
      decomposition of organic matter is relevant. The simple linear model proposed,
      and the related graphs, are shown to be useful tools for monitoring the main
      features of such a complex dynamic environmental system. The outlined approach to
      the considered complex data structure presents in a cognitive easy way (graphical
      outputs) the significant variations of the data, and allows for a detailed
      interpretation of the results of the monitoring campaign. Temporal and spatial
      effects are outlined, as well as those related to the depth in the water column.

PMID- 11529084
TI  - A new mussel certified reference material (CRM 477) for the quality control of
      butyltin determination in the marine environment.
AB  - The analytical techniques used for the determination of butyltin compounds in
      biological tissues are generally based on a succession of steps (e.g.,
      extraction, derivatization, separation, detection) which are all prone to
      systematic errors. An interlaboratory programme performed at the EU level and
      based on a stepwise approach has enabled one to identify and remove most of these
      errors and to improve considerably the state of the art so that certification of
      a mussel reference material has been made possible. This paper describes the
      preparation of this mussel reference material containing monobutyltin (MBT),
      dibutyltin (DBT) and tributyltin (TBT), the homogeneity and stability studies and
      the analytical work performed for the certification of the contents of MBT
      [Sn(C4H9)3+], DBT [Sn(C4H9)2(2+)] and TBT [Sn(C4H9)3+]. The results obtained by a
      group of expert EU laboratories are discussed along with the methods used to
      certify the mass fractions (based on dry mass) of monobutyltin (1.50 +/- 0.28 mg
      kg-1 as MBT cations), dibutyltin (1.54 +/- 0.12 mg kg-1 as DBT cations) and
      tributyltin (2.20 +/- 0.19 mg kg-1 as TBT cations). The paper also describes an
      attempt to certify the content of triphenyltin in this material which, although
      reasonable agreement was found among the participants' results, failed owing to
      the instability of this compound. This new material will be of great support to
      ensure the quality control of butyltin determination in shellfish, as carried out
      in environmental monitoring programmes.

PMID- 11529086
TI  - Ireland faces challenge on air quality; finalises IPC system.

PMID- 11529085
TI  - Collaborative study to improve the quality control of rare earth element
      determinations in environmental matrices.
AB  - In order to control the quality of rare earth determinations in environmental
      matrices, the Standards, Measurements and Testing Programme (formerly Community
      Bureau of Reference, BCR) of the European Commission has started a project, the
      final aim of which is to certify four types of matrices (tuna muscle, mussel
      tissue, aquatic plant and estuarine sediment) for their contents of a range of
      rare earth elements (Sc, Y and the lanthanides: La, Ce, Pr, Nd, Sm, Eu, Gd, Tb,
      Dy, Ho, Er, Tm, Yb and Lu). The elements U and Th were added to the study. The
      first part of this project consisted of an interlaboratory study which aimed to
      test the feasibility of preparation of environmental reference materials and to
      detect and remove most of the pitfalls observed in rare earth determinations.
      This paper presents the preparation of the four matrices for the intercomparison
      study and for the candidate reference material. The main results are presented of
      the interlaboratory study that was carried out prior to the certification
      campaign. This collaborative trial is the first attempt ever carried out at this
      scale to evaluate the state-of-the-art of rare earth determinations in the
      environment. Its impact on the improvement of chemical measurements will have
      positive effects on the comparability of data necessary for environmental
      monitoring.

PMID- 11529087
TI  - An approach to the assessment of the quality of environmental monitoring data.
AB  - This paper reports an approach to the assessment of the validity of environmental
      monitoring data--a 'data filter'. The strategy has been developed through the UK
      National Marine Analytical Quality Control (AQC) Scheme for application to data
      collected for the UK National Marine Monitoring Plan, although the principles
      described are applicable more widely. The proposed data filter is divided into
      three components: Part A, 'QA/QC'--an assessment of the laboratory's practices in
      Quality Assurance/Quality Control; Part B, 'fitness for purpose'--an evaluation
      of the standard of accuracy that can be demonstrated by activities in (A), in
      relation to the intended application of the data; and Part C, the overall
      assessment on which data will be accepted as usable or rejected as being of
      suspect quality. A pilot application of the proposed approach is reported. The
      approach described in this paper is intended to formalise the assessment of
      environmental monitoring data for fitness for a chosen purpose. The issues
      important to fitness for purpose are discussed and assigned a relative priority
      order on which to judge the reliability/usefulness of monitoring data.

PMID- 11529088
TI  - Quality assurance in measuring the elemental composition of the alga Fucus
      vesiculosus.
AB  - Algae are increasingly used for the purpose of environmental biomonitoring, for
      instance in the long-term program of the Federal Environmental Specimen Bank of
      Germany. Therefore, for the studies presented here, freeze-dried samples of Fucus
      vesiculosus collected from the North Sea shores were analyzed for a broad range
      of elements by instrumental neutron activation analysis (INAA), while inductively
      coupled plasma atomic emission spectrometry (ICP-AES) and mass spectrometry (ICP
      MS) were carried out on digests. The entire analytical procedures, including
      field sampling, cleaning of material, sample handling, determination of blanks
      and instrumental parameters, are described. Certified reference materials
      analyzed in parallel with real samples and intermethod comparisons were used for
      assuring the accuracy of the analytical data. Reproducibility of INAA
      measurements was between 4 and 6% depending on the element considered. Possible
      sources of uncertainty and variation of the contaminant origins are discussed.
      Boundary conditions for the performance of algae sampling within environmental
      monitoring programs and the application of this marine bioindicator for the
      purpose of controlling time-dependent and local differences in element patterns
      are presented.

PMID- 11529089
TI  - EPA moves against mercury and toxic chemicals.

PMID- 11529090
TI  - Japan sounds alarm on hormone disrupters.

PMID- 11529091
TI  - Detection of petroleum hydrocarbons at low ppb levels using quartz resonator
      sensors and instrumentation of a smart environmental monitoring system.
AB  - Petroleum hydrocarbon vapors at low ppb levels can be detected using a thickness
      shear mode resonator (TSMR) coated with a chemical-sensing overlayer, prepared by
      radiofrequency sputtering of porous sintered-polyethylene (PS-PE). The sensing
      capabilities of PS-PE sensors were profoundly affected by the sputtering methods;
      they were enhanced by the photo-excitation effect, and were reduced by
      carbonization and water treatment. The photo-assisted PS-PE sensor was extremely
      sensitive and could detect linear hydrocarbon (> C12) vapors below the ppb level.
      The time constant of the sorption curve, however, was large, indicating a slow
      sensing speed. Toward creating instrumentation for a smart environmental
      monitoring system, the TSMR sensors were arrayed on a circuit board equipped with
      a serial interface and signal processing chips of the oscillation drive and
      frequency counter. Co-sorption with water vapor at a relative humidity of about
      10% has almost no effect on the sensing ability of PS-PE sensors for 1,2,4
      trimethylbenzene. Conversely, it enhances the sensitivity of the TSMR sensor
      coated with a D-phenylalanine film. Upward shifts in the baseline are evident
      with elapsed time. However, a rigorous ten-cycle iteration test for 100 ppm
      toluene vapor demonstrated good reproducibility of the sensor's signals.

PMID- 11529092
TI  - The influence of geometry and draught shields on the performance of passive
      samplers.
AB  - Passive samplers provide an excellent opportunity to perform indicative
      measurements or establish a dense network of measuring sites. A drawback compared
      with conventional active measuring methods is the larger spread of results. This
      variation can, to a large extent, be attributed to the influence of temperature,
      sampler geometry and wind on sampling results. A proper design of sampler
      geometry and optimum choice of draught shield can reduce the influence of wind
      velocity on a badge type sampler to less than 10%. Wire mesh screens prove to be
      inadequate in damping turbulence. Filters give good results. Attention should be
      paid to the size and isolation value of the walls of the sampler to prevent
      thermal updrafts occurring within the sampler. Tube type samplers are less
      influenced by wind, provided that turbulence is prevented from influencing
      diffusion within the sampler.

PMID- 11529093
TI  - Workplace monitoring of hydrogen peroxide using titanyl-coated sorbents.
AB  - The current methods of sampling hydrogen peroxide, based on bubbling in acid
      solutions (titanium tetrachloride or titanium oxysulfate), are unsuitable for
      personal sampling. An alternative medium has been developed: silica gel coated
      with titanium oxysulfate. Sample tubes of this new sampling medium are suitable
      for personal sampling. The sampling performance is the same as that of the
      methods based on bubbling, but the tubes must be desorbed as soon as possible,
      even if the spectrophotometric analysis can be postponed. Special emphasis has
      been placed on the possible interference by peracetic acid, which is currently
      used in conjunction with hydrogen peroxide in the food industry.

PMID- 11529094
TI  - Urinary nickel concentrations and selected pregnancy outcomes in delivering women
      and their newborns among arctic populations of Norway and Russia.
AB  - The two objectives of this study were to compare urinary nickel excretion in
      pregnant women and their newborns living in the Murmansk and Arkhangelsk Counties
      of Russia with that in comparable Norwegian populations living in Finnmark and
      the city of Bergen and to assess the influence on pregnancy outcome of different
      risk variables, specifically urinary nickel concentrations and questionnaire
      based anamnestic information. Life-style information and urine samples were
      collected from 50 consecutive mother-infant pairs from hospital delivery
      departments in three Russian and three Norwegian communities. Pregnancy outcomes
      were verified from medical records. Urinary nickel excretion was significantly
      higher in the Russian communities, independent of the presence of a nickel
      refinery as a local environmental source. The birth weight and mean body mass
      index of the newborn children (BMIC) were significantly lower (p < 0.001) in the
      Russian groups, with or without adjustment for gestational age. A multivariate
      linear regression analysis indicated that maternal urinary nickel concentration
      had no impact on birth weight. The maternal body mass index (BMI) and maternal
      height were positive explanatory variables; maternal urinary creatinine is
      suggested as a weak negative factor. Smoking was shown to be a strong negative
      predictor only in the Norwegian group among whom there was a significantly higher
      smoking frequency (p = 0.005). The significant contribution of a country factor
      in the predictive model is interpreted to indicate that a number of important
      risk factors for low birth weight were not identified.

PMID- 11529095
TI  - Use of quadrupole GC-MS and ion trap GC-MS-MS for determining 3-hydroxy fatty
      acids in settled house dust: relation to endotoxin activity.
AB  - Gas chromatography-mass spectrometry (GC-MS) using a quadrupole instrument and GC
      tandem MS (GC-MS-MS) using an ion trap instrument were applied to determine 3
      hydroxy fatty acids (3-OH FAs) with 10-18 carbon chain lengths, specific
      components of the endotoxin (lipopolysaccharide, LPS) of Gram-negative bacteria,
      in 30 house dust samples. The two methods provided similar detection sensitivity
      for methyl ester/trimethylsilyl derivatives of the 3-OH FAs and allowed these
      acids to be distinguished from co-eluting 2-OH FA derivatives. The correlation
      coefficients between endotoxin activity (Limulus test) and the combined amounts
      of 3-OH C10, 3-OH C12, and 3-OH C14 were 0.60 and 0.61 when using GC-MS and GC-MS
      MS, respectively. The superior selectivity of GC-MS-MS was illustrated in
      analyses of sub-milligram amounts of dust, where the chromatograms achieved by GC
      MS were difficult to interpret due to a high background and several closely
      eluting compounds. GC-MS-MS is therefore preferable to GC-MS for determining 3-OH
      FAs in minute (sub-milligram) amounts of dust.

PMID- 11529096
TI  - Distributions of lead and cadmium in dust in the vicinity of a sewage sludge
      incinerator.
AB  - The content of lead and cadmium in surface dust within a 4 km radius of a sewage
      sludge incinerator has been investigated. Particular attention was given to Pb
      and Cd in different size fractions of dust, an aspect not explored in previous
      studies, and the differences between expressions of contamination as
      concentration or loading were examined. Despite suggestions from reports that
      sludge incinerators may have difficulty in complying with emission standards, the
      present investigation found little evidence for a major contribution to local
      pollution by the incinerator. Certainly, the highest Cd level was found some 2.2
      km downwind of the prevailing wind direction from the incinerator, suggesting
      some resultant contamination, although the levels do not appear to be excessive.
      Similar observations apply to Pb contamination of the area. While data of the
      type produced in this study contribute to an understanding of environmental
      quality, both loadings and levels need to be considered, as the implications of
      only consideration one of these may be limited and even misleading.

PMID- 11529097
TI  - Carbonate induced dissolution of uranium containing precipitates under cement
      leachate conditions.
AB  - The effects of carbonate on uranium (VI) solubility under aerobic and
      cementitious conditions have been investigated. The information is of relevance
      to low level nuclear waste disposal. Aqueous NaOH, KOH, Ca(OH)2 and a cement
      leachate solution were added to uranyl nitrate solution. Afterwards, increasing
      amounts of ammonium carbonate were added to re-dissolve the precipitates. The
      precipitates were characterised by means of X-ray powder diffraction (XRPD)
      measurements and modelling studies. The model calculations were performed using
      the MINTEQA2 speciation code, with an expanded database incorporating uranium
      stability constants taken from the HATCHES database. The measured and predicted
      amounts of CO3(2-) needed to dissolve the precipitates were compared. The
      knowledge gained from the 'pure' systems was used to rationalise the
      precipitation and re-dissolution behaviour observed in the leachate system. The
      lack of uranium solubility at low carbonate levels brought into question
      literature formation constants for UO2(OH)3- and UO2(OH)4(2-). An approximate log
      K value of 26.8 for K2U2O7 formation was estimated from the KOH results at pH 12.
      Generally, uranium solubilities are expected to be insignificant at low level
      nuclear waste sites because anaerobic conditions should persist. However, this
      study has demonstrated that solubility in leachate could rise at high pH and high
      carbonate levels, if aerobic conditions were to develop. Soluble U(VI) species
      would be formed. The novel part of the study has been to reproduce the effects
      and to correlate enhanced solubilities with model predictions. Consequently, the
      study has re-emphasised the need for appropriate environmental monitoring of such
      sites.

PMID- 11529098
TI  - Optimizing the removal of carbon phases in soils and sediments for sequential
      chemical extractions by coulometry.
AB  - We have developed a coulometric technique to optimize the removal of the
      carbonate and organic fractions for sequential chemical extractions of soils and
      sediments. The coulometric system facilitates optimizing these two fractions by
      direct real-time measurement of carbon dioxide (CO2) evolved during the removal
      of these two fractions. Further analyses by ICP-MS and alpha-spectrometry aided
      in interpreting the results of coulometry experiments. The effects of time,
      temperature, ionic strength and pH were investigated. The sensitivity of the
      coulometric reaction vessel/detection system was sufficient even at very low
      total carbon content (< 0.1 mol kg-1). The efficiency of the system is estimated
      to be 96% with a standard deviation of 8%. Experiments were carried out using
      NIST Standard Reference Materials 4357 Ocean Sediment (OS), 2704 Buffalo River
      Sediment (BRS), and pure calcium carbonate. Carbonate minerals were dissolved
      selectively using an ammonium acetate-acetic acid buffer. Organic matter was then
      oxidized to CO2 using hydrogen peroxide (H2O2) in nitric acid. The carbonate
      fraction was completely dissolved within 120 min under all conditions examined
      (literature suggests up to 8 h). For the OS standard, the oxidation of organic
      matter self-perpetuates between 45 and 50 degrees C, a factor of two less than
      commonly suggested, while organic carbon in the BRS standard required 80 degrees
      C for the reaction to proceed to completion. For complete oxidation of organic
      matter, we find that at least three additions of H2O2 are required (popular
      methods suggest one or two).

PMID- 11529099
TI  - Evaluation of the state-of-the-art of butyl- and phenyltin compound
      determinations in freshwater sediment prior to certification of a reference
      material.
AB  - In order to control the quality of butyl- and phenyltin compound determinations
      in sediment, the Standards, Measurements and Testing Programme (formerly BCR) of
      the European Commission has started a project, the final aim of which is to
      certify a freshwater sediment for its contents of a range of organotin compounds
      (mono-, di- and tributyltin, and mono-, di- and triphenyltin). The first part of
      this project involved an interlaboratory study which aimed to test the
      feasibility of preparation of candidate freshwater sediment reference material
      and to detect and remove most of the pitfalls observed in organotin
      determinations. This paper presents the main results of this interlaboratory
      study carried out prior to the certification campaign. The agreement obtained
      among laboratories for the six compounds determined was considered to reflect the
      state-of-the-art and was encouraging enough to decide upon the organisation of a
      certification campaign, which will be concluded in June 1999.

PMID- 11529101
TI  - Effect of freezing on the length of the penis in Nucella lapillus (L.).
AB  - When quantifying imposex in Nucella lapillus, two indices are used: the Vas
      Deferens Sequence Index (VDSI) and the Relative Penis Size Index (RPSI). Freezing
      and thawing increase the length of the penis in both male and female Nucella
      lapillus. In the population studied, this had no significant effect on the RPSI,
      but was potentially an important source of additional variance in the estimation
      of the mean penis length.

PMID- 11529100
TI  - Stability and storage problems in organotin speciation in environmental samples.
AB  - The stability of both tributyltin (TBT) and triphenyltin (TPT) in water,
      sediment, oysters and cockles was studied over a period of 18 months using
      several storage conditions. Butyltins were stable in unacidified sea-water stored
      in polycarbonate bottles in the dark at 4 degrees C for 7 months, but half of the
      TBT concentration was lost after 540 d. A comparable preservation time was
      achieved for butyltins stored on C18 cartridges at room temperature. However,
      phenyltins extracted from sea-water were stable for only 60 d stored on
      cartridges and even more pronounced losses (about 90% after 540 d) occurred when
      they were stored in either polycarbonate or Pyrex glass bottles. Losses of
      organotins were observed in sediments after air drying and pasteurization
      treatments using a freeze-dried sediment as a comparator, whereas both butyltin
      and phenyltin species remained stable in sediments stored at -20 degrees C for
      the 18 months tested, irrespective of the treatment used for stabilization. Air
      drying followed by pasteurization was shown to be superior to other treatments
      for the stabilization of organotin compounds in sediments stored at higher
      temperatures, but 30% of TBT was lost after 540 d at 25 degrees C. Finally,
      butyltins were stable in both frozen cockles and oysters in the dark over a 7
      month period and in freeze-dried samples stored at 4 degrees C for 5 months, but
      TBT losses of about 70% were observed after 540 d.

PMID- 11529103
TI  - Europe moves towards unified air policy.

PMID- 11529102
TI  - An unhealthy road.
AB  - With transport now the major source of many air pollutants, scientists need to
      fill in important gaps in our understanding of associated health risks.

PMID- 11529104
TI  - Transport holds back US air quality.

PMID- 11529105
TI  - Determination of metal-humic complexes, free metal ions and total concentrations
      in natural waters.
AB  - A comparison of two systems for the quantitation of metal-humic complexes and
      free metal ions, consisting of the separation by coupled ion exchange columns
      followed by detection by inductively coupled plasma mass spectrometry or cold
      vapour atomic fluorescence spectrometry, is presented. The systems evaluated
      comprised the serially coupled anion and cation exchangers, Sephadex A-25/Chelex
      100 and Dowex 1X8/Chelamine Metalfix. Separation and preconcentration of the
      species studied were accomplished with both systems, elution being carried out
      using 2 M HNO3. Total concentrations, metal-humic complex fractions and free
      metal ion fractions of Al, Ba, Cd, Co, Cu, Fe, Hg, Mn, Pb, Sr, U and Zn in nine
      natural waters were determined. Statistical evaluation of the data from the two
      cation exchange materials, including results for additional elements, showed
      better precision (for Al, Ba, Cr, Cu and Mo) and higher recoveries (Al, Ba, Cd,
      Fe, Sr and Zn) for Chelex 100 than Chelamine Metalfix for free metal ions. On the
      other hand, Chelamine Metalfix recovered a significantly greater amount of Ni.
      The amounts of metal-humic complexes were compared with modelled distributions of
      these species, and one advantage of the preferred Sephadex A-25/Chelex 100 system
      is that the elements studied are all correctly classified with respect to their
      binding strengths to humic substances, which is not the case with the Dowex
      1X8/Chelamine Metalfix pair. With the preferred system, metal-humic complexes can
      be reliably determined, as indicated by the results of equilibrium speciation
      modelling. However, comparison with the total concentrations showed statistically
      significant, non-quantitative recoveries of Al, Cu, Hg, Mn, U and Zn from some
      samples. Thus a combination of speciation and total concentration measurements is
      required to obtain a complete representation of the distribution of trace
      elements in natural waters.

PMID- 11529106
TI  - Biomonitoring of contaminated mine tailings through age accumulation of trace
      metals in the bank vole (Clethrionomys glareolus).
AB  - Lead, zinc and cadmium were determined in a range of tissues from laboratory-bred
      bank voles (Clethrionomys glareolus) exposed to elevated levels of dietary zinc
      (124 micrograms g-1). The pelletised diet was derived from vegetation harvested
      from the surface of a revegetated tailings dam at a modern Zn-Pb mine. Exposure
      regimes to the contaminated diet were 16, 32, 64, 128 or 256 days. Elevated
      levels of dietary zinc were not reflected in the individual tissue or total body
      concentrations. Marginal age accumulation of lead and cadmium was evident in the
      liver (Pb) and kidney (Pb and Cd). Tissue residues did not attain toxicologically
      significant concentrations. Animals inhabiting the grassland are considered to be
      at low ecotoxicological risk with respect to trace metals.

PMID- 11529107
TI  - Cadmium concentrations in human kidney in the UK: 1978-1993.
AB  - Almost 2700 samples of human renal cortex have been collected from throughout the
      UK over a 16 year period from 1978 to 1993. The mean Cd concentration was 19
      micrograms g-1 and the median 16 micrograms g-1. Smokers were, on average, about
      5 micrograms g-1 higher than non-smokers. Cd increased from low concentration in
      the young to a maximum of 23 micrograms g-1 in middle age followed by a decrease
      in old age. Subjects who had died of renal disease had lower Cd concentrations.
      Geographical variations in the UK are small and the concentrations appear to be
      static over the 16 year period. Some 3.9% of the population had Cd concentrations
      > 50 micrograms g-1, the critical level at which beta 2-microglobulin appears in
      urine.

PMID- 11529108
TI  - QUASIMEME laboratory performance study of the biological effects of tributyltin
      (imposex and intersex) on two marine gastropod molluscs.
AB  - The disruption of the endocrine systems of gastropod molluscs and consequential
      physiological changes (imposex and intersex) are used as biomarkers for
      environmental contamination by tributyltin compounds. The first international
      laboratory performance study on the determination of imposex and intersex in
      neogastropod molluscs, Nucella lapillus and Littorina littorea has been
      undertaken by the QUASIMEME (Quality Assurance of Information for Marine
      Environmental Monitoring in Europe) project. Samples of live gastropods were
      distributed and participants were asked to record shell height and sex, together
      with penis length and vas deferens sequence stage (VDS) in Nucella or the
      intersex stage (IS) and prostate length in Littorina. Calculations were made of
      vas deferens sequence index (VDSI) and the relative penis size index (RPSI) in
      Nucella and of intersex stage index (ISI) and the average female prostate length
      (FPrL) in Littorina. Thirteen (87%) of the 15 participating laboratories returned
      data. The remaining two laboratories asked to participate in later exercises. For
      Nucella, seven laboratories reported sex ratios significantly different from the
      reference laboratory data. Differences in penis length measurements between
      laboratories were largely random, although there were indications of systematic
      errors affecting the data from three laboratories. Seven laboratories reported
      satisfactory data (Z-score magnitude of Z < 2) for VDSI. The inclusion of a high
      proportion of sub-adults in the Nucella samples may have made separation of the
      sexes more difficult than in mature adults. The sub-adults will have had smaller
      pene than mature adults in the same population, and therefore any errors (random
      or systematic) in the measurement of penis length or observation of reproductive
      organs would have a potentially greater impact on the final reported values of
      the summary imposex indices. The Littorina sample did not show a high degree of
      intersex (ISI = 0.41). The laboratories could determine the sex of Littorina
      reliably and only one laboratory reported data significantly different from the
      reference laboratory. All except two laboratories reported satisfactory data for
      ISI.

PMID- 11529109
TI  - Imposex measurement in the dogwhelk Nucella lapillus (L.)--temporal aspects of
      specimen preparation.
AB  - The measurement of the Relative Penis Size Index (RPSI) in the dogwhelk Nucella
      lapillus (L.) depends upon reliable observations of the length of the penis (PL).
      Following removal of soft tissue from the shell, PL increases with time leading
      to a progressively greater over-estimation of the RPSI. The error is
      proportionally greater at low RPSI values. To retain comparability with previous
      data, it is suggested that dogwhelks should be examined as soon as possible after
      shell crushing.

PMID- 11529110
TI  - Establishment of a sampling strategy for the use of blue mussels as an indicator
      of organotin contamination in the coastal environment.
AB  - The application of the Mussel Watch concept to the assessment of chemical
      contamination in the coastal environment is still premature, since the
      relationship between the physiological and ecological aspects of blue mussels and
      the accumulation of contaminants in their soft tissues remains unclear. We cannot
      yet directly estimate with known confidence the degree of chemical contamination
      from the levels of contaminants in the soft tissues of mussels. An understanding
      of the source and range of variability in the tissue concentrations of
      contaminants is essential, and the establishment of a biomonitoring sampling
      strategy to minimize the effect of identified sources of variability is required.
      The present study was conducted to clarify the characteristics of organotin
      accumulation in blue mussels under various conditions in Tokyo Bay, and to
      establish an optimized sampling strategy of mussels as exposure indicators of
      organotin contamination in Japan. It was clear that the sample number, individual
      size, spawning activity and vertical habitat were factors causing a variation of
      tissue concentration. Based on a quantitative estimation of the variability of
      organotin concentration in mussel tissues under various physiological and natural
      conditions, we suggest that a composite sample of 30 mussels (3-5 cm in shell
      length), collected from the infralittoral zone prior to their spawning season, is
      essential to reduce the variability between individuals and to obtain
      reproducible analytical values at a sampling site. For monitoring sites where
      natural blue mussels cannot be collected, an alternative method of transplanting
      blue mussels from a relatively clean area would be required.

PMID- 11529111
TI  - Study of the effect of pH, salinity and DOC on fluorescence of synthetic mixtures
      of freshwater and marine salts.
AB  - In order to provide support for the discussion of the fate of organic matter in
      estuaries, a laboratory simulation was performed by changing freshwater ionic
      strength, pH and organic matter content. The change in spectroscopic
      characteristics caused by variations in salinity, pH and organic matter
      concentration in the filtered samples was observed by UV-Vis and fluorescence
      spectroscopy. The increase in emission fluorescence intensity of dissolved
      organic matter (DOM) due to increasing salinity (in the range 0 to 5 g l-1) is
      affected by the pH of the samples. The emission fluorescence intensity at the
      three maxima observed in the fluorescence spectra, is linearly correlated with
      dissolved organic carbon (DOC) concentration at several salinity values in the
      same sample. The increase in organic matter concentration caused a shift in the
      emission peak wavelength at 410 nm for several salinity values. We concluded that
      it is necessary to take into account the influence of salinity and pH on emission
      fluorescence of dissolved organic matter if it is to be used as a tracer in
      estuarine or near shore areas.

PMID- 11529112
TI  - An automatic monitor of formaldehyde in air by a monitoring tape method.
AB  - An automatic monitor has been developed for measuring formaldehyde in air using a
      sensitive tape for formaldehyde. It is based on the color change of the tape on
      reaction with formaldehyde. The porous cellulose tape, containing silica gel as
      an absorbent and impregnated with the processing solution containing
      hydroxylamine sulfate, Methyl Yellow (pH indicator; pH 2.9-4.0, red-yellow),
      glycerin and methanol, was found to be a highly sensitive means of detecting
      formaldehyde and maintains a stable sensitivity. When the tape was exposed to a
      sample of air containing formaldehyde, the color of the tape changed from yellow
      to red. The degree of color change was proportional to the concentration of
      formaldehyde at a constant sampling time and flow rate, and it could be recorded
      by measuring the intensity of reflected light (555 nm). The tape could be used to
      detect down to 0.08 ppm (World Health Organization standard) of formaldehyde with
      a sampling time of 30 min and a flow rate of 100 mL min-1. Reproducibility tests
      showed that the relative standard deviation of response (n = 10) was 3.8% for 0.1
      ppm formaldehyde. The monitor is simple, specific, capable of unattended
      operation and is recommended for both laboratory and field operation.

PMID- 11529113
TI  - Field intercomparison of diffusive samplers for measuring ammonia.
AB  - Agricultural production systems are recognised as a major source of atmospheric
      ammonia. Deposition of ammonia and ammonium may contribute to undesired changes
      in oligotrophic ecosystems. The continuous measurement of atmospheric ammonia
      requires expensive and sophisticated techniques and is performed only in a very
      restrict number of ambient air stations in Europe. Therefore, the application of
      passive samplers, which have the advantage of being easy to handle and cost
      efficient, is useful. In the past the comparability of different passive samplers
      must be considered as rather scarce. In a joint European project under the
      leadership of the GSF-Forschungszentrum fur Umwelt und Gesundheit, Neuherberg, in
      1997 a comparison of different passive ammonia monitoring methods was carried out
      in a prealpine rural site near Garmisch-Partenkirchen. It was considered valuable
      to include not only well established systems but also methods still being
      developed. For the comparative test ten working groups with different methods
      took part. A wet annular denuder system, which has been developed by the
      Netherlands Energy Research Foundation for on-line measurement of atmospheric
      ammonia, served as reference of passive methods. The experiment, which started in
      June and finished in December, showed that most of the passive samplers fulfil
      the requirements and can be recommended for further measurements. Additional
      measurements of meteorological parameters were performed to check the influences
      of different weather conditions on passive sampling.

PMID- 11529114
TI  - Towards sustainable pesticides.
AB  - In the light of increasing concern over the environmental impact of pesticides,
      we look at the evolution of national and international policies for sustainable
      pesticide use, and the associated data requirements.

PMID- 11529115
TI  - Perchlorate rockets to US national attention.

PMID- 11529116
TI  - Challenges for Central Europe.

PMID- 11529117
TI  - Pressure grows on phthalates.

PMID- 11529118
TI  - Worldwide progress on chemical assessment.

PMID- 11529119
TI  - Canada targets chemical toxics.

PMID- 11529120
TI  - Cancer warnings for creosote and bisphenol.

PMID- 11529121
TI  - Summary of environment-related research areas developed in the frame of the 5th
      Framework Programme of the European Commission.
AB  - Following the decision of the European Parliament and of the Council of 22
      December 1998, The European Commission has launched its Fifth Framework Programme
      for Research, Technological Development and Demonstration (RTD) which will run
      from 1999 to 2002. The activities will be carried out in the frame of four
      thematic programmes and three horizontal ones. The first calls for proposals were
      published in March 1999. Detailed information on the work programme of each
      activity is available through the Internet at the following address
      http://www.cordis.lu/fp5 and through direct contact with the programme's help
      desks. The present summary gives an outline of environment-related research
      activities covered by 5th FWP.

PMID- 11529122
TI  - AIRMON '99: the Third International Symposium on Modern Principles of Air
      Monitoring (Geilo, Norway, February 10th to 14th 1999).

PMID- 11529123
TI  - Sampling and characterization of individual particles in occupational health
      studies.

PMID- 11529124
TI  - Application of recent advances in aerosol sampling science towards the
      development of improved sampling devices: the way ahead.
AB  - This paper reviews the framework that underpins the development of a new
      generation of personal samplers capable of operating at much lower flowrates that
      those of the current generation and so capable of being used for exposure
      assessment not only for 'traditional' occupational populations (i.e., industrial
      workers) but also for people exposed to aerosols in the ambient atmosphere
      (including children). The opportunity for this new generation of samplers stems
      from the availability of very light and compact low-flowrate pumps. The
      development and deployment of such instruments presents: (a) physical challenges
      in terms of how to collect particle size fractions in a manner which is
      consistent with the new particle size-selective sampling criteria, and (b)
      analytical challenges in terms of how to quantitate the much smaller amounts of
      collected material that need to be analysed. The paper lays out the physical and
      analytical scenarios, and points the way forward to how such challenges can be
      overcome. Work is already in progress in several countries to develop prototype
      instruments for applications like those described.

PMID- 11529125
TI  - Biosensors in air monitoring.

PMID- 11529126
TI  - Measurement of vapour-aerosol mixtures.
AB  - A particular problem in connection with the measurement of hazardous substances
      is posed by substances or groups of substances which may occur simultaneously in
      vapour and aerosol form. It is possible that, during sampling, the distribution
      of the two phases on the sampling medium is subject to changes due to
      vaporisation of aerosol or condensation of vapour. For workplace assessment
      purposes, it makes sense to consider the sum of vapour and aerosol, which never
      changes. Only then can the results of different sampling systems be compared.
      There are several ways in which vapour-aerosol mixtures can be sampled. Combining
      adsorption tubes or denuders with filters is the most important. Twofold
      requirements must be considered in the development of such sampling. METHODS:
      Those applying to sampling systems for aerosols as well as those for vapour
      sampling systems. To satisfy the requirements resulting from these substances and
      groups of substances, BIA's personal sampling system (PGP) was extended. In
      addition to the sampling head for inhalable dust (GSP), originally designed for a
      flow rate of 3.5 L min-1, sampling heads for 0.5, 1 and 10 L min-1 were
      developed. Tests were conducted on these sampling heads, which all showed
      compliance with the requirements defined for inhalable fraction sampling. For the
      combined sampling of aerosol and vapour, a system was created which allows a
      filter and up to three usual adsorption tubes to be loaded simultaneously. The
      measuring methods for alkanolamines, inorganic acids and explosives are described
      to illustrate the use of the above PGP extensions and the framework conditions,
      account of which must be taken in the sample treatment.

PMID- 11529127
TI  - Determination of carbonyls using liquid chromatography-mass spectrometry with
      atmospheric pressure chemical ionization.
AB  - A liquid chromatographic method for the determination of aldehydes and ketones
      based on mass spectrometric detection is described. Recently developed modular
      derivatizing agents are employed for analysis. These hydrazine reagents, e.g. 4
      dimethylamino-6-(4-methoxy-1-naphthyl)-1,3,5-triazine-2-hydrazine (DMNTH), react
      with the carbonyl compounds with the formation of the respective hydrazones,
      which are separated by HPLC-MS with atmospheric pressure chemical ionization in
      the positive mode. Electrospray ionization may also be used for analysis.
      Particular focus is directed on various calibration approaches, including
      external calibration with standard solutions and internal calibration with a
      hydrazone standard of cyclobutanone, an aldehyde not likely to occur in real
      samples. A second approach for internal calibration is based on the 13C2-labelled
      acetaldehyde hydrazone standard. Different calibration approaches may then be
      used for the analysis of real samples. Limits of detection range from 2 x 10(-8)
      to 5 x 10(-8) mol L-1 for a series of hydrazones, including hydrazones of
      saturated aldehydes with alkyl chain lengths from 1 to 7 carbon atoms, and
      hydrazones of selected unsaturated and aromatic aldehydes as well as ketone
      hydrazones.

PMID- 11529128
TI  - Air pollution exposure monitoring and estimating. Part I. Integrated air quality
      monitoring system.
AB  - This paper presents an integrated exposure monitoring system, based on an
      expansion of existing air quality monitoring systems using dispersion modelling.
      The system allows: (1) identifying geographical areas whose inhabitants are most
      exposed to ambient pollution; (2) identifying how many people in an area are
      exposed to concentrations of pollution exceeding air quality guidelines; (3)
      describing the exposure of population subgroups (e.g. children); (4) planning
      pollution abatement measures and quantifying their effects; (5) establishing risk
      assessment and management programs, and (6) investigating the short- and long
      term effects of both pollutants and pollution sources on public health. The
      effect of pollution is rarely very large and in order to discover it, exposure
      estimation must provide data that reflects both spatial and temporal variations.
      Estimates of pollution exposure are obtained using an integrated approach that
      combines results of measurements from monitoring programs with dispersion
      calculations. These values can serve as estimates for individual short-term or
      long-term exposure. The grouped data allows the expression of ambient pollution
      concentrations as the spatial distribution of estimates such as the mean or 98th
      percentile of such compounds as SO2, O3, NO2, PM10 and PM2.5. This integrated
      approach has been combined into a single software package, AirQUIS.

PMID- 11529129
TI  - Air pollution exposure monitoring and estimation. Part II. Model evaluation and
      population exposure.
AB  - The air pollution dispersion model EPISODE has been developed at the Norwegian
      Institute for Air Research (NILU) over the past several years in order to meet
      the needs of modern air quality management work in urban areas. The model has
      recently been used as a basis for exposure calculations of NOx and NO2 in order
      to assess the effects of different traffic diversion measures on health and well
      being for the residents in the Valerenga-Ekeberg-Gamlebyen area in Oslo. Here we
      describe some results from the most recent evaluations of the model for NOx and
      NO2 at station Nordahl Brunsgate in Oslo for the period 1 October 1996-19
      November 1996. In addition examples of population exposure calculations for Oslo
      performed during the winter period of 1995-96, are also presented.

PMID- 11529130
TI  - Air pollution exposure monitoring and estimation. Part III. Development of new
      types of air quality indicators.
AB  - The temporal pattern of exposure to a specific compound may affect health in
      several ways. Exposure to pollution can have short-term effects or long-term
      effects. For some compounds there is a threshold under which there is no presumed
      measurable effect, whereas for other compounds, there is no presumed threshold.
      For short-term effects, the exposure to a high concentration of a compound one
      day may either increase or decrease the response if values of the same compound
      become high again the next day. Adaptation to effects of short-term exposure to
      ozone, for example, is reported. Similarly, health response to sudden high peaks
      of concentration may also possibly differ in effect from those to peaks attained
      more gradually. For long-term effects of some compounds, the cumulative exposure
      may be more decisive in influencing health. This paper proposes and describes in
      detail several air quality indicators that reflect the time variability and the
      episodic nature of air pollution exposure, as an attempt to represent the
      temporal aspects of pollution exposure that may have important effects on health.
      Mean concentrations, 98th percentile and maximum values are the traditional
      indicators for estimating exposure. The temporal variability of particulate
      matter (PM10) and NO2, however, is here described by means of: (1) the rate of
      change of pollution as the difference between two consecutive hourly or daily
      values, and of (2) episodes, described in terms of number, duration and inter
      episode period, maximum concentration in the episode, and integrated episode
      exposure.

PMID- 11529131
TI  - Air pollution exposure monitoring and estimation. Part IV. Urban exposure in
      children.
AB  - In the winter of 1994, 2300 school-age children in Oslo participated in a panel
      study of the role of traffic pollution on the exacerbation of diseases of the
      respiratory system and other symptoms of reduced health and well being in
      children. The children filled out a diary daily with information for five time
      points over six weeks. In order to quantify exposure-effect relationships for the
      symptoms, individual exposure to NO2 and particulate matter (PM2.5) was
      estimated, using the DINEX method a combination of information from the diary as
      to the children's whereabouts during the five time points each day, coupled with
      continuous dispersion modelling. An individual exposure estimate for each time
      point for each child was defined. Individual exposure estimated using dispersion
      modelling can be used to examine patterns of exposure such as isolating
      geographic areas with higher concentrations or describing concentrations of
      pollution by time of day. The diary allowed the time-use of the children to be
      described.

PMID- 11529132
TI  - Air pollution exposure monitoring and estimation. Part V. Traffic exposure in
      adults.
AB  - In Oslo, traffic has been one of the dominating sources of air pollution in the
      last decade. In one part of the city where most traffic collects, two tunnels
      were built. A series of before and after studies was carried out in connection
      with the tunnels in use. Dispersion models were used as a basis for estimating
      exposure to nitrogen dioxide and particulate matter in two fractions. Exposure
      estimates were based on the results of the dispersion model providing estimates
      of outdoor pollutant concentrations on an hourly basis. The estimates represent
      concentrations in receptor points and in a square kilometre grid. The estimates
      were used to assess development of air pollution load in the area, compliance
      with air quality guidelines, and to provide a basis for quantifying exposure
      effect relationships in epidemiological studies. After both tunnels were taken in
      use, the pollution levels in the study area were lower than when the traffic was
      on the surface (a drop from 50 to 40 micrograms m-3). Compliance with air quality
      guidelines and other prescribed values has improved, even if high exposures still
      exist. The most important residential areas are now much less exposed, while
      areas around tunnel openings can be in periods exposed to high pollutant
      concentrations. The daily pattern of exposure shows smaller differences between
      peak and minimum concentrations than prior to the traffic changes. Exposures at
      home (in the investigation area) were reduced most, while exposures in other
      locations than at home showed only a small decrease. Highest hourly exposures are
      encountered in traffic.

PMID- 11529133
TI  - Air pollution exposure monitoring and estimation. Part VI. Ambient exposure of
      adults in an industrialised region.
AB  - This paper presents methodology and results of a dynamic individual air pollution
      exposure model (DINEX) that calculates the hourly exposure for each adult in a
      panel study. Each of over 260 participants, through the use of a diary, provided
      information used in the model to calculate his/her personal, individualised
      exposure. The participants filled out the diary daily, hour by hour, over two,
      two month periods. The exposure assessment model coupled the diary information
      and results of an indoor/outdoor measurement program, with the results of
      dispersion modelling on an hourly basis for an industrial area in Norway. The
      estimated air pollution concentrations from the dispersion model, based on
      continuous meteorological measurements, were calibrated with air pollutant
      concentrations measured continuously.

PMID- 11529134
TI  - Validation of a diffusive sampler for NO2.
AB  - A diffusive sampler for NO2, Willems badge, was validated in laboratory
      experiments and field tests. The collecting reagent for NO2 in the sampler is
      triethanolamine, and the analysis is based on a modified colorimetric method, the
      Saltzman method. The analysis was performed by a flow injection analysis (FIA)
      technique. The sampling rate for the sampler was determined to be 40.0 ml min-1.
      There was no effect of NO2 concentration or relative humidity on sampling rate,
      and the influence of sampling time was found to be small. The detection limit was
      4 micrograms m-3 for a 24 h sample. The capacity is high enough to allow sampling
      of 150 micrograms m-3 for 7 days, which is twice the recommended Swedish short
      term (24 h) guideline value as a 98-percentile over 6 months. In field tests, the
      sampler performed well, even at wind speeds higher than 2 m s-1, and at low
      temperatures. The overall uncertainty of the method was 24%. The sensitivity and
      capacity of the method also make it suitable for personal sampling for 2-8 h in
      working environments.

PMID- 11529135
TI  - Pentachlorophenol in indoor environments. Does a single measurement of air and
      dust concentrations represent the contamination?
AB  - In order to be able to make a decision, as to whether a room or building has a
      health-endangering pentachlorophenol (PCP) concentration, usually the PCP
      concentrations in air and settled dust are measured. The variability of the PCP
      concentration in indoor air and dust was studied. Air and dust samples were taken
      from 75 rooms in 30 buildings with suspicion of application of PCP-containing
      wood preservatives. Sampling was repeated four times within 18 months. Thirty-six
      rooms were reconstructed within the study; 39 rooms had unchanged contamination
      status during the study. The four times repeated measurements of PCP
      concentrations in air and dust in these rooms showed large variations of the
      measured values. The variability of the results is to a large extent in the same
      range as the measured values. The observed relative standard deviation of the PCP
      concentrations in air and dust does not depend on the average PCP concentration
      detected in the individual rooms.

PMID- 11529136
TI  - The effect of wind direction on the observed size distribution of particle
      adsorbed polycyclic aromatic hydrocarbons on an inner city sampling site.
AB  - An investigation of the variability in the size distribution of particle adsorbed
      polycyclic aromatic hydrocarbons (PAHs) on an inner city sampling site showed
      differences depending on the wind direction. Particle size distributions of PAHs
      from outdoor air sampling were measured in Munich from 1994 to 1997. The sampling
      site is located northeast of a crossing with heavy traffic and southwest of a
      large inner city park. Depending on the wind direction, three different size
      distributions of particle adsorbed PAHs were observed. The maximum PAH
      concentration on very small particles (geometric mean diameter 75 nm) was
      observed with wind from west to southwest coming directly from the crossing area
      or the roads with heavy traffic. The maximum PAH concentration on particles with
      geometric mean diameter of 260 nm was found on days with wind from the built-up
      area north of the sampling site. On particles with geometric mean diameter of 920
      nm the maximum PAH concentration was found on days with main wind directions from
      northeast to east. On these days the wind is blowing from the direction of the
      city park nearby. The distribution of particle adsorbed PAHs within different
      particle size classes is substantially influenced by the distance of the sampling
      site from strong sources of PAH loaded particulate matter.

PMID- 11529137
TI  - Air sampling of fungal spores on filters. An investigation on passive sampling
      and viability.
AB  - In this study, glycerol was tested as a collection substrate for passive
      bioaerosol sampling. Filters (mixed cellulose acetate and nitrate) were soaked in
      glycerol and exposed for an aerosol from three different fungal species:
      Penicillum commune, Aspergillus versicolor and Paecilomyces variotii. The passive
      sampling method was compared with a closed-face polycarbonate filter sampling
      method. Exposure was performed in an exposure chamber. The total number of spores
      was determined by microscopic techniques, and the cultivable number was
      determined by cultivation on Malt Extract Agar dishes. The glycerol soaked filter
      demonstrated a good correlation with the closed-face sampler with regard to the
      total count. Spores stored in a pumped filter cassette were not affected by
      storage for up to 7 days. On the other hand, the culturability of the spores was
      markedly decreased after 1 day when stored on glycerol soaked filters.

PMID- 11529139
TI  - Quantification of re-evaporated mass from loaded fibre-mist eliminators.
AB  - Airborne lubricant emissions are a serious health hazard for employees in the
      metal working industry. The basic components of lubricants are oils and additives
      for adapting the properties to achieve the process demands. The oils used in
      lubricants are either mineral, synthetic or of biological origin. The lubricants
      are used as water-emulsions and also as straight oils. Extreme process conditions
      cause considerable amounts of aerosol and vapour emissions of lubricants into the
      working environment. Fibre filters are used in industrial demisters for pollution
      control and also for sampling purposes. Re-evaporation of separated lubricants
      from loaded fibre filters causes increased vapour emissions. Quantification of
      lubricant vapour emission was the subject of this research. An apparatus and an
      appropriate procedure for measuring the dynamic behaviour of evaporative losses
      from fibre filters were developed. The test piece of a loaded fibre filter was
      fixed in a sampling probe according to VDI 2066. The vapour concentration of
      organic compounds in downstream air was measured in real-time by using a photo
      ionisation detector (PID). The PID was checked by sampling the vapour on an
      oleophilic adsorbent resin, solvent extraction and quantitative IR analysis and
      also gravimetrically. The two basic processes of filtering volatile aerosols are,
      on the one hand, collecting droplets on the fibres and, on the other hand, the
      evaporation of collected liquid. These two processes had to be separated in order
      to measure the increase of the vapour concentration caused by the tested fibre
      filter. The experiments were carried out using pure dodecane and hexadecane in
      order to avoid difficulties due to the unknown chemical composition of lubricant
      vapour. The variation of the air flow and the initial liquid mass on the filter
      covered the relevant range for industrial fibre demisters and for sampling
      methods based on collecting aerosols on fibre filters. It was found that the
      downstream air was saturated with lubricant vapour for a wide range of filter
      loads and filtration velocities. From the results obtained it can be concluded
      that loaded industrial filter systems emit air with saturation vapour
      concentration throughout their operation. Hence, vapour emissions can be
      estimated easily if the saturation vapour pressure and the mean relative
      molecular mass are known. Moreover, results obtained from measurements of filters
      with low loads confirm that the phase transition from liquid to vapour is
      influenced by the identified process parameters. This is relevant for measurement
      methods using fibre filters for sampling volatile aerosols. A semi-empirical
      model to estimate the evaporative losses for low loadings is proposed. However,
      further research is necessary to determine the full range of parameters that are
      relevant for evaporative losses from filters loaded with low masses of aerosols.

PMID- 11529138
TI  - Assessment of occupational exposure to diesel fumes--parameter optimization of
      the thermal coulometric measurement method for carbon.
AB  - 'Elemental' carbon (EC) is used as a surrogate to assess occupational exposure to
      diesel soot. EC thermal analysis needs complete desorption of organic compounds
      from the soot particles prior to analysis in order to minimize positive
      interferences and artefacts. The desorption of the organic compounds can be
      considered as the major step which influences the reliability of the EC
      determination. A systematic study was carried out to investigate the different
      parameters of influence such as desorption temperature, desorption duration,
      heating rate and type of the sample on the desorption efficiency. It was found
      that temperature and duration are the major parameters of influence on the
      desorption efficiency. The influence of the sample load can be seen as a measure
      of the pyrolysis susceptibility of the sample. An optimized temperature program
      is proposed.

PMID- 11529140
TI  - Classification of particles from the farm environment by automated sizing,
      counting and chemical characterisation with scanning electron microscopy-energy
      dispersive spectroscopy.
AB  - About 60,000 particles in 288 aerosol samples collected during farm work have
      been characterised with automated particle analysis using scanning electron
      microscopy (SEM) and energy dispersive X-ray spectrometry (EDS). Based on EDS
      analysis of materials with known composition (potato flour, alpha-quartz, K
      feldspar and beta-wollastonite), criteria were developed for classification of
      particles as: (1) organic, (2) silicon-rich (silica), and (3) other inorganic
      particles. The reproducibility of the relative mass proportions in dust samples
      collected during farm work was 0.078 when approximately 200 particles were
      characterised per sample. Field samples from the farm environment showed clear
      differences in composition. Generally, inorganic particles dominated the particle
      mass. The proportion of the organic particle mass was highest for tending of
      swine and poultry, 55 and 38% respectively. Silica particles amounted to 10 to
      20% of the total mass during handling crops, e.g. grain, straw, hay, potatoes,
      and onions. It seems likely that the results can be used in etiologic studies,
      but further validation would be needed for quantitative purposes.

PMID- 11529141
TI  - Determinations of PCB within a project to develop cleanup methods for PCB
      containing elastic sealant used in outdoor joints between concrete blocks in
      buildings.
AB  - Determinations of PCB were carried out as part of a project aimed at developing
      cleanup methods for PCB-containing elastic sealant used in outdoor joints between
      concrete blocks. The goals of the project were to develop methods, which minimise
      the spread of PCB to the outdoor environment and to indoor air, and which keep
      the PCB levels as low as reasonably possible in the workplace environment whilst
      removing the elastic sealant. The following PCB determinations were carried out:
      (1) concentration in the elastic sealant; (2) concentration in the concrete close
      to the sealant; (3) concentration in soil; (4) concentration in the indoor air;
      and (5) concentration in the air in the workplace environment. The cleanup
      process consisted of a number of different steps: (1) cutting the elastic sealant
      with an oscillating knife; (2) grinding the concrete with a mechanical machine;
      (3) sawing the concrete with a mechanical saw and (4) cutting the concrete with a
      mechanical chisel. In all these different steps a high capacity vacuum cleaner
      connected to the machines was used. The elastic sealant contained 4.7 to 8.1%
      total PCB of a technical product with a composition most similar to Clophene A40.
      The concrete close to the sealant (first 2 mm) contained 0.12 and 1.7% total PCB
      at two different places. The pattern of the PCB in the concrete resembled that of
      the sealant. PCB concentrations in the soil from the ground close to the building
      were 0.1 and 0.3 ppm at two different places before the remedial action. The
      source of the PCB in the soil is most likely the sealant as the PCB pattern is
      similar for the two materials. The PCB levels in the workplace air at the
      beginning of the project, when the techniques were not fully developed, were
      generally above the occupational exposure limit of 10 micrograms m-3 (up to 120
      micrograms m-3). Later when the techniques were optimised to better take care of
      dust and gases produced during the cutting and grinding etc., the levels were
      below or close to 10 micrograms m-3. The pattern of the PCB in the workplace air
      was different from that of the sealant and contained higher levels of lighter
      components. The PCB concentrations in the indoor air were measured before and
      during the remedial process. The levels were around 600 ng m-3 and there was no
      significant increase during the removal of the sealant. The PCB level after the
      remedial action will be measured later. The pattern of the PCB in the indoor air
      was different from that of the sealant as well as from that of the workplace air.
      Higher levels of the lighter PCB were present indoors compared to the composition
      in both workplace air and in sealant. Extracts of PCB were analysed by GC-MS with
      a SIM method (selected ion monitoring). Standard procedures were used for
      extraction of solid materials. For the air samples an OVS tube was used with XAD
      2 as adsorbent. The filter and adsorbent were extracted with toluene. This work
      shows that it is important to perform remedial action of PCB-containing elastic
      sealant as: (1) there is a spread of PCB to the indoor air giving high enough
      concentrations to make this the main PCB load on humans living in the apartments
      studied in this project; (2) large amounts are spread to the soil from these
      sealants; and (3) many of the PCB-containing elastic sealants used need to be
      changed from a functional perspective.

PMID- 11529142
TI  - Reduction and avoidance of lubricant mist demands an integrated assessment
      approach.
AB  - A case study to identify major factors for lubricant mist exposure covered 15
      metal machining sites. The investigation included milling, turning, drilling and
      grinding applications. Systematic analysis considered all relevant data
      concerning the machine tool, the lubricant and the suction plant. The efficiency
      of the implemented maintenance program at the installed filter systems was
      checked by concentration measurements immediately before and after service. All
      performed measurements of lubricant aerosol and vapor loads upstream and
      downstream of the installed filter systems were carried out according to VDI 2066
      and BIA 3110, respectively. The selection criteria for the sites to be
      investigated, the systematic nature of the data acquisition and the procedure of
      the analysis are demonstrated in detail by performing comparisons between
      selected applications using emulsions and those employing straight oil for
      lubrication. The results of the study identify recirculation of ventilated air as
      the major source of workplace exposure to airborne lubricant emissions. More than
      60% of the demisters investigated emit air at total lubricant loads (aerosols and
      vapor) above the limit of 20 mg m-3 at any time of operation; which also means
      immediately after service. A common reason for exceeded aerosol loads in
      recirculated air is e.g. the fact that the type of filter system applied is often
      not suitable for the separation problem. Loads of lubricant vapor are usually
      higher at the processes which use water emulsions as lubricant. In a quarter of
      the cases the limits were exceeded solely due to high vapor loads even
      immediately after service. The exposure can be reduced by replacing the
      lubricant, installation of a vapor separation plant or avoiding air
      recirculation. Maintenance time of the demisting system and aerosol separation
      efficiency of state-of-the-art demisting systems can be expanded by
      implementation of enhanced preliminary filter stages. This study confirms that
      appropriate service measures lower both aerosol emissions and lubricant vapor
      concentrations due to the reduction of exposed oil-wetted surfaces. The performed
      measurements show no significant relationship between loads of airborne
      lubricants and the type of machining process. Therefore, investigations at a much
      more detailed level have to be performed. However, the individual assessment of
      any workplace due to the complex situation remains essential.

PMID- 11529143
TI  - The fate and persistence of polychlorinated biphenyls in soil.
AB  - The fate and persistence of PCBs 28, 52, 101, 138, and 180 artificially
      introduced into three soils was studied under a variety of field conditions for
      up to 415 d following initial contamination. A relationship was detected between
      ln Koa (octanol/air partition coefficient) and the experimentally observed first
      order loss rate constant that was statistically significant at at least the 90%
      level in all but one instance. In nearly all experiments, PCB persistence was
      greater in soils of higher organic carbon content. Soil temperature and moisture
      content were also indicated as important influences on persistence. Significantly
      longer half-lives were observed in a soil in which initial PCB contamination had
      occurred ca. 1 year previously. A mass balance showed the most likely mechanism
      of loss to be volatilisation. Losses attributable to aerobic biodegradation could
      not be ruled out, but those due to leaching, uptake by biota, and soil erosion
      were demonstrated to be negligible. First-order rate constants (Kv) were
      determined for volatilisation of the same congeners from soil under a variety of
      controlled laboratory scenarios. Multiple linear regression analysis (MLRA)
      showed the most important influences on kv to be ln Koa (adjusted for soil
      temperature) and soil organic carbon content. Limited evidence was observed for a
      relationship between kv and soil moisture content, but not water flux. When
      tested against field measurements, the MLRA-derived relationship between kv and
      independent variables predicted to within a factor of 2.5, the persistence of
      PCBs 28, 52, and 101, However, it did not account for the influence of the age of
      contaminant association with the soil, soil moisture content or water flux, and
      failed to function for soils of high organic content, or where ln Koa exceeds ca.
      23.

PMID- 11529144
TI  - An investigation of the origin and mobility of phosphorus in freshwater sediments
      from Bort-Les-Orgues Reservoir, France.
AB  - In order to assess the origin and the potential mobility of phosphorus (P) in the
      sediment of the Bort-Les-Orgues Reservoir, France, two sequential extraction
      schemes, i.e., the SMT (modified Williams method) and the Golterman schemes, were
      compared. Finally, the potential mobility of P in this sediment was estimated
      from results of sequential extraction. The SMT method appeared to be more
      satisfactory than the Golterman method, which is in accordance with results from
      a study currently carried out in the framework of the European programme
      Standards, Measurements and Testing. Iron-bound P and organic P were the dominant
      forms of P in the sediment; these forms are likely to be released at the
      sediment/water interface in case of anoxia and could diffuse into the water
      column, thus increasing the risk of eutrophication in this sensitive reservoir.
      The P stock (330 +/- 66 t) is not negligible and should be taken into account in
      any restoration project of the reservoir. The SMT procedure seems promising and
      will provide, in the near future, a valuable tool for water managers in the field
      of lake restoration.

PMID- 11529145
TI  - Thermodynamic influences on size fractionated measurements (PM 2.5, PM 10) of
      ambient aerosols.
AB  - Mass concentrations of PM 10 and PM 2.5 are planned as new standards for the
      monitoring of ambient air quality in the European Union. Standard procedure is
      the removal of particles > 10 microns and > 2.5 microns aerodynamic diameter,
      respectively, by impaction in a preseparator. Different samplers work according
      to different principles of flow control. The influence of ambient temperature,
      pressure and relative humidity on different devices is calculated to estimate the
      comparability of various aerosol samplers. Therefore, the effects of these
      ambient factors on the volume flow as well as on the cut-off dp50 are
      investigated. In a second step, the influence of relative humidity on the flow
      control device is calculated. The results show that the cut-off shifts (up to
      6.4%) for varying ambient conditions. Therefore, the influence on the impaction
      process should not be neglected and an 'ideal sampler' would measure temperature,
      pressure and relative humidity and adapt the volume flow to avoid a systematic
      error in the cut-off.

PMID- 11529146
TI  - Doing what comes naturally.
AB  - With high-tech remediation technologies proving too expensive for all but the
      most seriously polluted sites, scientists and regulators are looking to the
      restorative powers of Nature to clean-up contamination. Effective implementation
      of so-called 'natural attenuation' techniques relies crucially on high quality
      environmental analysis.

PMID- 11529147
TI  - EU unveils new air pollution policy.

PMID- 11529148
TI  - WHO tackles water and transport.

PMID- 11529149
TI  - Baltic states face waste challenge.

PMID- 11529150
TI  - Irish water quality patchy.

PMID- 11529151
TI  - Finland improves water environment.

PMID- 11529152
TI  - Europe divided on phthalate migration tests.

PMID- 11529153
TI  - EPA's selenium revision heads into murky waters.
AB  - As the US EPA revises its standards for selenium in fresh water, a heated debate
      rages between government scientists, who say that existing standards must be
      tightened because selenium contamination is widespread, and industry scientists
      who believe that it is an environmental oddity. Fish, crustaceans and birds
      appear to be uniquely sensitive to even modest increases in environmental
      concentrations of this element. To set new standards, EPA must find a way to take
      into account an emerging understanding of selenium's complex geochemistry.

PMID- 11529154
TI  - Living with risk.

PMID- 11529155
TI  - Synthetic musks in environmental samples: indicator compounds with relevant
      properties for environmental monitoring.
AB  - Synthetic musks (nitro and polycyclic musks) are a group of chemicals offering a
      wide range of important properties for environmental monitoring programs. They
      are produced as odorous chemicals and added to a wide variety of perfumes,
      toiletry products and other household products. As such, they are directly
      applied in cosmetic products or in washed textiles to the human body in
      considerable concentrations and accumulate owing to dermal resorption. In
      addition, synthetic musks also enter the environment via waste water treatment.
      Several polycyclic musks are chiral. By using chiral gas chromatographic methods,
      it is possible to determine the enantiomeric ratio and assess their
      bioavailability. Although an comprehensive quality assurance program must be
      followed during the analysis of synthetic musks in environmental samples, the
      determination of these compounds is not very demanding and can be carried out by
      a standard analytical laboratory specialising in trace analysis of organic
      pollutants. Owing to the pheromone-like behavior of some synthetic musks, the
      induction of receptors in olfactory systems should be investigated. For HHCB
      (1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta[g]-2-benzopyran, e.g.,
      Galaxolide), three-dimensional structural similarities with androstenone (5 alpha
      androst-16-en-3-one), a mammalian steroid pheromone, were found, which support
      the hypothesis of HHCB as an artificial pheromone. Owing to their environmental
      abundance, their relation to human activities and their potential for pheromone
      like environmental behavior, synthetic musks are especially valuable as future
      indicator chemicals for environmental monitoring.

PMID- 11529156
TI  - Data needs for occupational epidemiologic studies.
AB  - Data needs in an epidemiologic study can appear to be substantial in light of the
      other responsibilities of an industrial hygienist. Many of the data needed for
      this type of investigation, however, are already collected for other exposure
      assessment purposes. To increase understanding of this concept, the data needs
      for the major purposes for conducting an exposure assessment are identified. The
      purposes include determining compliance; implementing industrial hygiene
      programs, such as personal protective and respiratory equipment, hazard
      communication training, and medical surveillance; investigating health complaints
      and worker concerns; investigating tasks or engineering control effectiveness;
      investigating toxic tort or worker compensation claims; and conducting
      epidemiologic studies. A comprehensive exposure assessment system is then
      described that incorporates the data needs for all these purposes, including
      epidemiologic studies. The data needs of epidemiologic studies and how the data
      are used are then described and illustrated with examples taken from published
      epidemiologic studies.

PMID- 11529157
TI  - Personal ammonia sensor for industrial environments.
AB  - The realisation of an opto-chemical ammonia sensor suitable for personal
      monitoring tasks is described, comprising a cyanine dye immobilised in a
      microporous glass thin film. The fabrication of sensor platforms incorporating
      embossed grating couplers provides a compact optical design with effective
      waveguiding characteristics, resulting in reversible ammonia sensitivity in the 5
      100 ppm range in under 2 min. Cross-sensitivity of sensor response with water and
      other potential interferents is considered.

PMID- 11529158
TI  - Development of a personal monitoring method for nitrogen dioxide and sulfur
      dioxide with Sep-Pak C18 cartridge sampling and ion chromatographic
      determination.
AB  - Personal monitoring methods for the determination of hourly integrated
      concentrations of NO2 and SO2 in ambient air have been developed. Triethanolamine
      (TEA)-impregnated C18 Sep-Pak cartridges were used to collect NO2 and SO2
      simultaneously. After sampling, NO2 and SO2 as their nitrite, nitrate, sulfite
      and sulfate analogues were stripped from the cartridges with a solution of 5%
      methanol in distilled, deionized water (DDW) and then determined by ion
      chromatography. Laboratory tests were conducted to evaluate the sampling rate,
      collection and recovery efficiencies, breakthrough volumes, absorption capacity,
      interference and sample stability on the cartridge during storage. NO2 and SO2
      detection limits of 0.3 and 0.4 ppb respectively for 1 h samples were obtained.
      Recoveries for both NO2 and SO2 exceeded 85%.

PMID- 11529159
TI  - Measuring strategies and monitoring of the indoor environment.
AB  - This paper presents key elements on which to base the design of a strategy for a
      particular indoor environment measurement task. Starting from a general strategy
      for responding to occupant complaints and conducting epidemiological and
      intervention studies the paper concentrates on selected key elements, with focus
      on air contaminants. Strategies for grouping of occupants with the purpose of
      exposure assessment should aim at optimising exposure contrast between groups,
      and grouping according to buildings may not be the proper choice. Occupant
      exposure can be measured by personal sampling or constructed from measured
      concentrations in microenvironments and activity patterns. The cause of temporal
      and spatial variability is discussed and guidance is given on the number of
      samples needed to detect a given change in true concentration level. The sick
      building syndrome (SBS) is defined as those situations where a high proportion of
      building occupants are complaining about mucous membrane or skin irritation,
      general symptoms. When investigating SBS, questionnaires should be used to
      collect structured information from occupants on perception of environmental
      conditions, psychosocial factors and symptoms. There is as yet no consensus on
      choice of length of reference period for reporting symptoms and for estimating
      exposure. Finally, methods for identifying and quantification of sources of air
      contaminants are discussed, including lab-scale or full-scale simulation, on-site
      measurement of source emission, air monitoring, surface sampling, and modelling.

PMID- 11529160
TI  - Measurements of fractionated gaseous mercury concentrations over northwestern and
      central Europe, 1995-99.
AB  - Although it makes up only a few per cent. of total gaseous mercury (TGM) in the
      atmosphere, the fraction of oxidised (divalent) mercury plays a major role in the
      biogeochemical cycle of mercury due to its high affinity for water and surfaces.
      Quantitative knowledge of this fraction present in mixing ratios in the parts-per
      10(15) (ppq) range is currently very scarce. This work is based on approximately
      220 data for divalent gaseous mercury (DGM) collected during 1995-99 in ambient
      air. Over the course of the measurements, the sampling and analytical methods
      were modified and improved. This is described here in detail and includes
      transition from wet leaching and reduction procedures to thermo-reductive
      desorption, the use of annular as well as tubular denuders and adoption of an
      automated sampling system. The concentration of DGM exhibited a strong seasonal
      behaviour in contrast to atomic gaseous mercury, with low values in winter and
      maximum values in summer. The DGM/TGM ratios were frequently found to be below
      the detection limit (< or = 1%) and in the range 1-5%. A trend of diurnal DGM
      patterns was observed and implies photolytically induced sources. Scavenging of
      DGM during rain events was also noticed.

PMID- 11529161
TI  - Determination of acrylic acid in air by using diffusion denuder tubes combined
      with HPLC technique.
AB  - A procedure for the determination of atmospheric acrylic acid in air at the
      microgram m-3 to mg m-3 level is described. Diffusion-based sampling, designed to
      discriminate gaseous analytes from their particulate counterparts, has been used.
      Acrylic acid is collected with an efficiency of > 98% in tubular denuders coated
      with sodium hydroxide-barium hydroxide-hydroquinone monomethyl ether, and
      analyzed by high performance liquid chromatography with UV absorbance detection.
      The detection limit is 2.9 micrograms m-3 at a flow rate of 0.5 L min-1 and 30
      min sampling time. A precision (p = 0.95, n = 10) of 7.5% of the overall
      procedure was achieved at the 100 micrograms m-3 level. Results of laboratory
      studies concerning the effect of the coating reagent and the relative humidity on
      the sampling efficiency as well as possible interferences, in particular by
      ozone, and the elimination of these interferences are discussed. This method was
      developed to monitor workplace atmospheres as well as ambient air in industrial
      environments.

PMID- 11529162
TI  - Determination of selected microbial volatile organic compounds by diffusive
      sampling and dual-column capillary GC-FID--a new feasible approach for the
      detection of an exposure to indoor mould fungi?
AB  - A new, analytically valid procedure is described to assess the exposure of human
      beings to the so-called microbial volatile organic compounds (MVOCs) in air. The
      method can be used routinely for large sample numbers and is especially valuable
      as a basis for further research on the correlation between single MVOCs and
      indoor mould growth. The procedure is based on the fact that fungi produce a
      variety of volatile organic compounds, such as 3-methylbutan-1-ol, 3-methylbutan
      2-ol, fenchone, heptan-2-one, hexan-2-one, octan-3-one, octan-3-ol, pentan-2-ol,
      alpha-terpineol, and thujopsene, which they emit into the indoor environment.
      Using diffusive samplers, these MVOCs are adsorbed onto charcoal during a
      sampling interval of four weeks. The described method is thus superior to
      existing methods which use short-term active sampling. After desorption with
      carbon disulfide, the MVOCs were determined by dual-column gas chromatography
      with flame ionization detection using the large-volume injection technique for
      sample introduction. The detection limits ranged between 0.15 and 0.53 microgram
      m-3, within-series precision was found to range between 6.5 and 19.0%, and
      recovery was between 77 and 118%. The procedure has been successfully applied in
      the context of a large field study to measure the indoor MVOC exposure in
      children's rooms of 132 dwellings. The objective of the study was to examine the
      relation between indoor mould growth, the indoor MVOC exposure and the prevalence
      of adverse health effects. Information about mould formation has been obtained by
      a questionnaire and by the determination of colony forming units of mould fungi
      in mattress dust. With the exception of 3-methylbutan-2-ol, fenchone, nonan-2
      one, octan-2-one, and thujopsene, indoor air concentrations of all MVOCs under
      investigation were significantly higher inside damp and mouldy dwellings. From
      the primary MVOCs under investigation, 3-methylbutan-1-ol, hexan-2-one, heptan-2
      one, and octan-3-ol were found to be most reliable indicators for mould
      formation. A correlation was also found between selected MVOCs and the occurrence
      of mould species in mattress dust. Aspergillus sp. correlated with heptan-2-one,
      hexan-2-one, octan-3-ol, octan-3-one, and alpha-terpineol, while the occurrence
      of Eurotium sp. was correlated with higher indoor air concentrations of 3
      methylbutan-1-ol, 3-methylbutan-2-ol, heptan-2-one, hexan-2-one, octan-3-ol, and
      thujopsene. Children living in dwellings with elevated MVOC levels had a higher
      prevalence of asthma, hay fever, wheezing, and irritations of the eyes. These
      positive associations persisted after controlling for confounding factors such as
      age, sex, body-mass index, number of siblings, social status, passive smoking,
      type of heating, and ventilation habits. However, they were not statistically
      significant. This lack of significance may be a result of the small number of
      investigated samples.

PMID- 11529163
TI  - A catalogue of urban hydrocarbons for the city of Leeds: atmospheric monitoring
      of volatile organic compounds by thermal desorption-gas chromatography.
AB  - A method has been developed for the speciation and quantitative determination of
      hydrocarbons in urban air in the city of Leeds. Hydrocarbons were pre
      concentrated by adsorbent tube air sampling and analyzed using thermal desorption
      and gas chromatography with flame ionization detection and structural
      confirmation by mass spectrometric detection. While automated volatile organic
      compound (VOC) analyzers produced data for a maximum of about 30 compounds
      simultaneously, with the method described here, a total of 68 C6-C12 hydrocarbons
      were measured simultaneously in one analysis at parts per billion (ppb) levels.
      Several monitoring surveys were performed, one during the winter of 1993 and the
      other in the summer of 1994, at a number of sites to investigate the levels of
      VOCs identified in the urban air of Leeds.

PMID- 11529164
TI  - Ultrasonic extraction and portable anodic stripping voltammetric measurement of
      lead in paint, dust wipes, soil, and air: an interlaboratory evaluation.
AB  - Recent studies have demonstrated the utility of ultrasonic extraction (UE),
      followed by portable anodic stripping voltammetry (ASV), for the on-site
      determination of lead in environmental and industrial hygiene samples. The aim of
      this work was to conduct an interlaboratory evaluation of the UE-ASV procedure,
      with a goal of establishing estimates of method performance based on results from
      collaborative interlaboratory analysis. In this investigation, performance
      evaluation materials (PEMs) with characterized lead concentrations were used for
      interlaboratory testing of the UE-ASV procedure. The UE-ASV protocol examined has
      been promulgated in the form of two separate national voluntary consensus
      standards (one for UE and another for electroanalysis, which includes ASV). The
      PEMs consisted of characterized and homogenized paints, soils, and dusts (the
      last of which were spiked onto wipes meeting national voluntary consensus
      standard specifications), and air filter samples (mixed cellulose ester membrane)
      generated using characterized paints within an aerosol chamber. The lead
      concentrations within the PEMs were chosen so as to bracket pertinent action
      levels for lead in the various sample matrices. The interlaboratory evaluation
      was conducted so as to comply with an applicable national voluntary consensus
      standard that can be used to estimate the interlaboratory precision of a given
      analytical test method. Based on the analytical results reported by the
      participating laboratories, relative standard deviations (RSDs) for repeatability
      and reproducibility were computed for three different lead contents of the four
      PEMs. RSDs for repeatability were 0.019-0.100 for paints; 0.030-0.151 for soils;
      0.085-0.134 for dust wipes; and 0.095-0.137 for air filters. RSDs for
      reproducibility were 0.127-0.213 for paints; 0.062-0.162 for soils; 0.085-0.134
      for dust wipes; and 0.114-0.220 for air filters. With the exception of one of the
      air filter samples and one of the paint samples, the precision estimates were
      within the +/- 20% precision requirement specified in the US Environmental
      Protection Agency National Lead Laboratory Accreditation Program (NLLAP). The
      results of this investigation illustrate that the UE-ASV procedure is an
      effective method for the quantitative measurement of lead in the matrices
      evaluated in this study.

PMID- 11529165
TI  - Determination of N-acetyl-S-(N-methylcarbamoyl)cysteine (AMCC) in the general
      population using gas chromatography-mass spectrometry.
AB  - Carbamoylation of glutathione, peptides and DNA is thought to be one of the most
      important reactions occurring in an organism after exposure to nitrosoureas,
      methylformamides or isocyanates. The carcinogenic effects of carbamoylation are
      not yet fully clarified. Although carbamoylation is known to occur after
      occupational exposure, it has never been reported in the general population. To
      clarify the situation, we investigated the levels of N-acetyl-S-(N
      methylcarbamoyl)cysteine (AMCC) in urine samples from persons without
      occupational exposure using a sensitive and specific method (gas chromatography
      mass spectrometry, GC-MS). AMCC is the degradation product of N
      methylcarbamoylated glutathione. The clean-up procedure of urine samples includes
      two liquid-liquid extraction steps and solid phase extraction using a cation
      exchange resin to separate AMCC from other urinary components. N,N
      Dimethylpropionic acid amide (DMPA) is used as internal standard. During the
      preparation of the samples, AMCC is converted to ethyl-N-methylcarbamate (EMC) in
      the presence of anhydrous potassium carbonate (K2CO3) and ethanol. The
      reliability and accuracy of this method have been proven in detail. The relative
      standard deviation for the within-series imprecision for three different
      concentrations was determined to be between 10.9% and 14.3%, while the relative
      standard deviation for the between-day imprecision was between 11.3% and 14.8%.
      The mean recovery for AMCC was determined to be between 79.2% and 85.6%. The
      limit of detection for the simultaneous measurement of two fragment masses was 30
      micrograms L-1. Using this GC-MS method, we analysed urine samples from 42
      individuals of the general population in order to determine their urinary
      excretion of AMCC. It was identified in 40 samples. The mean concentration was 40
      micrograms L-1. AMCC can be formed in two ways. The first possibility is the
      dietary intake of isothiocyanates, especially methyl isothiocyanate, which is a
      component of wine and cruciferous vegetables (such as cabbage, turnips and
      cress). During the metabolism of isothiocyanates in humans, the sulfur is partly
      exchanged for oxygen resulting in the formation of the corresponding isocyanate
      derivatives. The other possibility is the physiological formation of AMCC. In
      humans, this may occur via a two step process: carbamoylation and methylation, or
      vice versa. However, as AMCC was identified in about 95% of urine samples, and
      the standard deviation for the level of AMCC excreted was low, physiological
      formation seems to be the more probable pathway.

PMID- 11529166
TI  - Biomonitoring of antimony in environmental matrices from terrestrial and limnic
      ecosystems.
AB  - Elder and poplar leaves from various sampling sites were studied with respect to
      their antimony content. Moreover, a retrospective determination of Sb was
      performed in representative limnic and terrestrial samples of the Federal
      Environmental Specimen Bank of Germany which have been collected over 14 years.
      The analytical procedure is based on an open vessel acid digestion of freeze
      dried biological samples and the subsequent quantification of Sb in the digests
      by flow injection hydride generation atomic absorption spectrometry. Strict
      quality control schemes were applied to the entire procedure to guarantee
      accurate and precise results. No long-term changes of the Sb concentrations were
      found in spruce shoots or poplar leaves from different sampling sites. However,
      spruce shoots from a semi-natural region showed concentrations of Sb
      (approximately 22 ng g-1; range: 17-29 ng g-1) that were approximately four times
      lower than in corresponding samples from an urban-industrialized area. The
      analysis of virgin and washed elder leaves revealed that approximately 20-30% of
      the Sb is present on the leaf surface. Sb levels in elder leaves ranged from 5.2
      +/- 0.3 ng g-1 in samples from Argentina to 589 +/- 30 ng g-1 in leaves collected
      directly beside a motorway in Germany. Similarly, poplar leaves from Argentina
      and Chile showed about 4 ng Sb g-1, whereas 150 ng Sb g-1 was found in poplar
      leaves from Germany. The lowest concentrations of Sb were determined in digests
      of pigeon eggs (approximately 2 ng g-1), bream liver (approximately 4 ng g-1) and
      deer liver (approximately 6 ng g-1). A similar pattern of Sb concentrations in
      spruce shoots, leaves or liver samples from an industrialized area and an
      agrarian ecosystem in Germany was established. Concentrations of Sb in elder
      leaves were closely associated with car traffic, giving maximum concentrations of
      589 ng g-1 directly beside a motorway, 207 ng g-1 50 m from the motorway and 153
      ng g-1 in a close residential area.

PMID- 11529167
TI  - Continuous flow methods for evaluating the response of a copper ion selective
      electrode to total and free copper in seawater.
AB  - This work describes the development of an instrument for measuring free and total
      copper in seawater by continuous flow analysis (CFA) with an Orion copper (II)
      ion selective electrode (CuISE). Sample analysis times are reduced considerably
      by using an extrapolation technique based on the fitting of an empirical
      mathematical expression to the electrode time-response curve enabling a
      prediction of the final equilibrium potential. CuISE measurements in seawater
      samples containing nanomolar levels of total copper can be very time consuming,
      and this predictive approach significantly reduces sample analysis time, and
      improves sample throughput. The time taken to measure pCu in seawater to a
      precision of +/- 0.1, using conventional potentiometry, varies considerably
      depending on the condition of the electrode membrane but can be reduced by a
      factor of 3-6 (typically from 60 to 10 min) by using the extrapolation technique
      in conjunction with CFA. Details are given of the protocols used for
      preconditioning the CuISE. The system can be used as a portable instrument for
      field measurements or for shipboard measurements of free copper in seawater.
      Extrapolated equilibrium potentials are within +/- 0.5 mV of true steady state
      values.

PMID- 11529168
TI  - Distribution of iron and manganese in the Seine river estuary: approach with
      experimental laboratory mixing.
AB  - The physico-chemical behaviour of iron and manganese has been observed during
      many surveys covering various hydrodynamic conditions in the Seine river estuary
      system. The results obtained confirm the non-conservative behaviour of these two
      metals. Generally, dissolved iron exhibits non-conservative removal and shows a
      rapid decrease in low salinity; it is moved from fresh waters with high
      concentrations to saline waters with very low concentrations. This can be
      attributed to the flocculation processes as confirmed by laboratory experiments.
      Dissolved manganese versus salinity curves exhibit a peak concentration in the
      low salinity zone. Laboratory mixing experiments have been undertaken comparing
      iron and manganese adsorption/desorption from suspended material versus salinity,
      using a series of water samples collected in the up-river and marine regions in
      order to assess the importance of particulate material and salinity on iron and
      manganese distributions. The salinity was controlled by varying the marine to
      fresh water ratio. The reaction kinetics aspect is developed in more detail for
      manganese in the last series of remobilization experiments starting from a stock
      of suspended particles collected in the upstream river site (Caudebec) in
      mixtures of waters, according to time and salinity. This study has allowed us to
      show that iron and manganese behaviour in the Seine estuary is strongly
      influenced: (i) by the high turbidity zone and by the presence of calcium
      carbonate which could stabilise the Mn(II) form; and (ii) by the increase of
      salinity, calcium, magnesium and suspended matter concentrations and by complex
      formation.

PMID- 11529169
TI  - A study of exposure standards in Russia and the role of occupational hygiene.
AB  - This paper is the result of an investigation carried out in February 1997, which
      set out to learn about the development and application of occupational health
      standards, and in turn approaches to occupational environmental monitoring, in
      Russia, and to see how these were similar to, or different from, what takes place
      in other countries. The enquiry involved face-to-face meetings with senior
      Russian occupational health scientists and officials. It was confirmed that
      Russian occupational exposure standards are very stringent and provide a very
      high level of protection of workers. However, they are difficult to enforce, and
      it is suggested that the development of a strong and distinctive occupational
      hygiene discipline and profession in Russia would provide a "bridge" to enable
      more effective implementation and interpretation of those standards.

PMID- 11529170
TI  - Ensuring quality in long term environmental monitoring for chemical speciation.
AB  - The awareness regarding quality assurance (QA) and quality control (QC) for
      environmental monitoring has considerably increased in the past few years,
      especially with respect to the determination of chemical species, since errors
      occurring at various levels may considerably affect the interpretation of results
      (e.g. studies of toxic impact, geochemical pathways, etc.). QA for environmental
      analysis covers a broad range of activities from sample collection to laboratory
      work and the approach for ensuring quality data should be considered in a global
      context. However, whereas great emphasis has been placed on QA within the
      laboratory, there have been few systematic attempts to evaluate risks of
      discrepancies related, for example, to field manipulations. The situation is even
      worse when monitoring is applied to relatively new fields such as chemical
      speciation. This paper outlines some of the main aspects of quality control of
      environmental analysis, including the validation of methods, sampling and sample
      handling, storage, etc., with special emphasis on the monitoring of chemical
      forms of elements (e.g. species of tin, mercury, lead and selenium).

PMID- 11529171
TI  - Public environmental information: access or excess?
AB  - Amongst the mass of academic papers and policy reports it is easy to forget that
      scientists and regulators are not the only ones concerned about the environment.
      The public has an interest too. Aided by modern technology and increasing legal
      rights, the man in the street has access to environmental information as never
      before. In this article we review recent developments in public assess and what
      these mean for 'the experts'.

PMID- 11529172
TI  - Cadmium tops EU agenda.

PMID- 11529173
TI  - Europe's 'weather forecast'.

PMID- 11529174
TI  - Momentum grows for phthalate ban.

PMID- 11529175
TI  - Environmental monitoring of genetically modified crops.
AB  - Genetically modified (GM) crops are now approved for commercial use in several
      world areas. In terms of commercial acreage, the majority of these products
      possess either herbicide tolerance or insect protection traits. Prior to
      commercialization, each product underwent a country specific review of
      environmental safety data by independent regulatory authorities. Registration was
      granted after review of the data allowed authorities to conclude that the risks
      were minimal or manageable when balanced with the benefits. As a condition of
      registration, insect resistance management (IRM) has been imposed for insect
      protected products in most countries. Other world areas have reviewed similar
      data packages and have not yet been able to grant registration for commercial
      release. Post-registration environmental monitoring of GM crops is viewed in some
      world areas as a means of enabling approvals by addressing uncertainty that
      exists with this technology. Questions such as, who should monitor and who should
      pay for it, how should monitoring be conducted, what information is necessary to
      collect and how long should a given product be monitored are yet to be answered.
      Monitoring methods could be general (surveys and questionnaires) or specific
      (scientific studies to address specific questions). Independent research
      currently underway in countries where GM crops are commercial involves monitoring
      the benefits as well as the risks of these products. Experience with other
      products has shown that monitoring of GM crops will be of value only if the
      questions are clearly defined, the methods are appropriate and the end points
      (data collected) are interpretable.

PMID- 11529176
TI  - Evaluating the environmental effects of the GM revolution.
AB  - In the US, cradle of genetically modified crops, agricultural scientists and
      regulators are already tackling one environmental issue, and rushing to determine
      the magnitude of another.

PMID- 11529177
TI  - Genetically modified organisms and monitoring.
AB  - The genetic modification of organisms for food use has raised serious concern
      about the potential for adverse effects on the environment, ecosystems and on the
      health of humans and animals. As a relatively new technology, its impacts remain
      uncertain but could range from disturbances to the genetic functioning of
      individual organisms to a reduction in the biodiversity of farmland. As a result,
      the question of how to monitor for potential impacts is beset with problems. The
      fact that genetic modification can be used on a range of organisms for a variety
      of purposes means that those developing monitoring systems will need to be as
      imaginative as those developing GMOs. In the case of genetically modified
      organisms (GMOs) for food use, concern has focussed on the transfer of genes to
      other organisms, the potential for effects on non-target organisms, or on the
      health of humans and animals, and the likelihood of adverse effects on wildlife
      due to changes in farming practice. As with other new and unfamiliar
      technologies, genetic modification is also plagued by the problem of uncertainty.
      Novel genes are inserted randomly into the genome of the host organisms, and this
      leads to the possibility of unexpected effects. Unanticipated environmental
      disasters, such as the concentration of persistent organic pollutants in
      ecosystems at high latitudes, have highlighted the need for monitoring despite
      the obvious difficulties inherent in monitoring for unexpected effects.

PMID- 11529178
TI  - EU acts against phthalates.

PMID- 11529180
TI  - US firms slam EU over risk.

PMID- 11529179
TI  - Scientists back GM crops.

PMID- 11529181
TI  - Progress on Great Lakes clean-up.

PMID- 11529182
TI  - EU struggles with ozone and acid deposition.

PMID- 11529183
TI  - Determination of rotenoids and piperonyl butoxide in water, sediments and
      piscicide formulations.
AB  - Rotenone is a naturally occurring insecticide and piscicide (fish poison) found
      in many leguminous plants. This paper describes high-performance liquid
      chromatography (HPLC) methods for the quantitative analysis of rotenone's
      principal biologically active components (rotenone, tephrosin, rotenolone,
      deguelin) and the synergist piperonyl butoxide (PBO) in various media. Compounds
      were separated on a C18 reversed phase column with an acetonitrile-0.025 M
      phosphoric acid mobile phase and detected by UV absorbance or fluorescence (PBO
      only). Solid phase extraction (SPE) was used in either coupled (on-line) mode
      with a C18 concentrator column or automated off-line mode using Empore C18 disks.
      The on-line extraction efficiency was improved significantly by adding small
      amounts of methanol to water. Method detection limits (MDLs) for rotenoids and
      PBO in reagent water were 0.3 and 2 micrograms L-1, respectively, with optimal
      recoveries ranging from 90% to 99%. Aquatic sediments were extracted with
      methanol and the extracts were diluted in water prior to analysis by coupled SPE
      HPLC. In wet sediments, detection limits were approximately 20-100 micrograms kg
      1 with recoveries of 71% to 87%. Sonication in dimethyl sulfoxide (DMSO) followed
      by dilution in acetonitrile and filtration allowed determination of the active
      ingredients in powdered rotenone formulations. Details of sample preparation,
      cartridge column cleanup and analyte confirmation are provided.

PMID- 11529184
TI  - Fluorescence quenching of polycyclic aromatic compounds by humic substances. Part
      1. Methodology for the determination of sorption coefficients.
AB  - An introduction to the methodology of fluorescence quenching measurements as an
      experimental tool for investigating the sorption of hydrophobic organic
      substances by dissolved organic matter (OM) is given. Special attention is paid
      to the implications of inner-filter effects (IFEs) on the determination of
      sorption coefficients. The essential aspects of the theoretical description of
      IFEs are outlined and various procedures for the IFE correction of fluorescence
      quenching measurements in the presence of dissolved OM are presented. Geometric
      parameters relevant for the quantitative description of IFE applying a 90 degrees
      arrangement between fluorescence excitation and detection are determined by
      different methods, newly developed or adapted from the literature, for the
      fluorescence spectrometer used in this work. Moreover, an experimental validation
      of the applicability of different IFE correction procedures is performed. In
      order to evaluate the variations of sorption coefficients that result from the
      use of different IFE correction procedures, the quenching of the fluorescence of
      the well-known polycyclic aromatic compound pyrene by a commercially available
      humic substance in aqueous solution is investigated. Compared to the apparent
      sorption coefficient, which is obtained without any IFE correction, the sorption
      coefficients determined with the correction of primary IFE or with the correction
      of primary and secondary IFE are on average ca. 40 or 60% lower. The application
      of different IFE correction procedures allows the determination of sorption
      coefficients with appropriate precision of +/- 15%.

PMID- 11529185
TI  - A method for measuring dermal exposure to multifunctional acrylates.
AB  - UV-curable acrylates are used increasingly for coating wood surfaces in the
      furniture industry. One of the active components, tripropylene glycol diacrylate
      (TPGDA), is known to be both an allergen and irritant to the skin. Methods to
      measure dermal exposure to skin irritants and allergens, such as acrylates, are
      insufficient for exposure assessment and there is none for this compound. The aim
      of this investigation was to develop a skin and surface sampling method, based on
      tape stripping, and a gas chromatographic method for quantitative analysis for
      assessing occupational skin exposure to multifunctional acrylates. Twelve
      adhesives were tested for their efficiency to remove TPGDA and UV-coating from a
      glass surface, the skin of guinea pigs and human volunteers employing the tape
      stripping method in order to find the best performing tape. Variables that affect
      removal efficiency such as the applied dose and its retention time on the skin,
      tape adhesion time on the skin, and the number of strippings required to detect
      the contaminant from the skin were studied. Fixomull tape performed the best
      during sampling and analysis and had the most consistent removal efficiencies for
      the studied substances. The average removal efficiency with a single stripping at
      the 2 microliters TPGDA exposed skin sites was 85% (RSD = 14.1), and for UV-resin
      exposed sites 63% (RSD = 20.2). The results indicated that this method can be
      used for measuring dermal exposure to multifunctional acrylates efficiently,
      accurately, and economically. This method provides a sensitive and powerful tool
      for the assessment of dermal exposure to multifunctional acrylates both from the
      skin and from other contaminated surfaces in occupational field settings.

PMID- 11529186
TI  - Determination of alkylamine permeation through protective gloves using aliphatic
      amine pads.
AB  - A quantitative study of alkylamine permeation through a glove material using
      Permea-Tec aliphatic amine pads, used for the detection of chemical breakthrough
      of protective clothing, was performed for triethylamine following a microwave
      extraction process and gas chromatographic analysis. Triethylamine exhibited >
      99% adsorption on the pads at a spiking level of 729 ng (1.0 ml). Triethylamine
      showed recoveries from 63 to 90% (RSD < or = 5%) over the range 0.2-1.0 ml (146
      729 ng) applied to pads. The ASTM F739 standard and direct permeability testing
      procedures were used to determine breakthrough times for five protective glove
      materials using triethylamine as a challenge chemical. Breakthrough times for six
      protective gloves were determined ranging from 40 s to > 4 h. The quantitative
      concentration of triethylamine on the pads following permeation through the
      gloves was also determined, ranging from 101 to 103 ng cm-2 (382-386 ng per pad).

PMID- 11529187
TI  - The evaluation of a low resolution fourier transform infrared (FTIR) gas analyser
      for monitoring of solvent emission rates under field conditions.
AB  - The applicability of a low resolution (8 cm-1) Fourier transform infrared (FTIR)
      gas analyser with an absorption path length of 3 m was evaluated for the on-line
      monitoring of organic solvent mixture emissions in a flexographic ink
      manufacturing plant. The on-line monitoring revealed that the highest variations
      of solvent concentrations, up to three decades, occurred in the exhaust air. The
      FTIR analyser with a dynamic range of four decades covers well the concentration
      ranges typically found in the exhaust air and in the workroom air of ink
      manufacturing plants. The average emission rate of solvent mixture based on a
      sampling period of two days was 1.8 kg h-1 consisting of mainly ethanol (70%),
      ethyl acetate (15%) and propan-2-ol (11%). The detection limits of the analyser
      for the solvent compounds ranged from 0.3 to 4.3 mg m-3 and the measurement
      uncertainty was less than 10% in the concentration range of 8-15,000 mg m-3.
      These characteristics make the apparatus appropriate for most industrial hygiene
      applications. An FTIR spectrophotometer, equipped with an multipoint sampling
      unit, facilitates rapid identification of solvent components, real-time display
      of concentration data relevant to workroom air and environment monitoring as well
      as process control. Furthermore, the on-line concentration information enabled a
      rapid selection of representative sampling locations. The spectrophotometer is
      transportable, rugged and relatively simple to calibrate even in a hostile
      industrial environment.

PMID- 11529188
TI  - Establishing normal values for nickel in human lung disease.
AB  - People working in the nickel refining industry are known to have a higher
      concentration of nickel in lung tissue than the general population. To be able to
      evaluate a potential nickel exposure from other sources, e.g., welding, it is
      important to have sufficient data on what is normal for a local population.
      Several local factors such as the content of nickel in air and soil can have a
      significant impact on this so-called normal value. As almost all surgical
      equipment contains nickel, the sampling process can in itself be a source of
      contamination. The scope of this work was to investigate if there was any
      measurable contamination from the sampling instruments routinely used in
      hospitals, and if the presence of a nickel refinery had any effect on the nickel
      content in the lungs of the general population. Autopsy lung tissue samples were
      collected in situ from 50 people who had lived in the county of Vest Agder in
      Norway. Two samples were collected from each person; one with a regular scalpel
      (Swann-Norton) and forceps, and one with a titanium knife and plastic forceps.
      None of the persons had any known connection to the nickel refinery. The samples
      were collected at random and no special attention was given to age, sex and place
      of residence. The autopsies were performed according to Norwegian law and in
      understanding with the next of kin. The arithmetic mean value +/- s of nickel was
      0.64 +/- 0.56 microgram g-1 and 0.29 +/- 0.20 microgram g-1 dry weight,
      respectively, for samples collected with a regular scalpel and a titanium knife
      (P < 0.0001). For people who lived 8 km and closer to the refinery by the time of
      death, the nickel content was 0.41 +/- 0.19 microgram g-1 and for those who had
      lived between 8 and 70 km away from the refinery it was 0.18 +/- 0.13 microgram g
      1 (P < 0.015). No statistical difference was established between results for
      males and females. Previous investigations have shown that the nickel content in
      lung tissue varies in the so-called normal population. This work has shown that
      factors such as sampling equipment and place of residence have an impact on the
      results. It thus demonstrates that reliable background values can presumably only
      be obtained by collecting samples from individuals not exposed to known
      environmental nickel sources and to use nickel-free instruments in the sampling
      process.

PMID- 11529189
TI  - Correlation of urinary nickel excretion with observed 'total' and inhalable
      aerosol exposures of nickel refinery workers.
AB  - An investigation of the relationship between observed nickel aerosol exposures
      and urinary nickel excretion was undertaken at a Scandinavian nickel refinery.
      The goal of the study was to assess the impact of nickel aerosol speciation, the
      use of particle size-selective sampling instrumentation and adjustment of urinary
      levels for creatinine excretion on the usefulness of urinary nickel excretion as
      a marker for exposure. Urinary nickel measurements and paired 'total' and
      inhalable aerosol exposure measurements were collected each day for one week from
      refinery workers in four process areas. The mean observed urinary nickel
      concentration was 12 micrograms L-1 (11 micrograms of Ni per g of creatinine).
      The strongest relationships between urinary excretion and aerosol exposure were
      found when urinary nickel levels were adjusted for creatinine excretion and when
      exposure to only soluble forms of nickel aerosol was considered. No significant
      difference was observed between measures of 'total' and inhalable aerosol in the
      ability to predict urinary excretion patterns. In the light of these results, it
      is recommended that consideration be given to the chemical species distribution
      of nickel aerosol in the use of urinary nickel measurements as a screening tool
      for cancer risk in occupationally-exposed populations.

PMID- 11529190
TI  - Cement for stabilisation of industrial residues containing heavy metals.
AB  - A method aimed at decreasing the toxicity of heavy metals [namely, Zn(II) and
      Cr(III)] in real polluted residues by immobilisation has been developed. The
      residues were processed either with two cement-type stabilisers or lime. The
      cement-type stabilisers were Portland cement and Depocrete SM/2 at the self
      generated pH (ca. 11) which afforded physical as well as chemical potential for
      the immobilisation of heavy metals. The other stabiliser, lime, reduced organic
      compounds, thus favouring the decrease of the chemical oxygen demand (COD) and
      endowing the residue with better mechanical properties for transport. After
      leaching the stabilised residues using the standard leaching test [Order
      13/10/89, Boletin Oficial del Estado (BOE) 270 10/11/89], three ways for
      establishing the toxicity of the treated residues were used, namely: (1) the
      ecotoxicity test using Photobacterium phosphoreum (DIN 38 412); (2) determination
      of the concentration of heavy metals by atomic absorption spectrometry (AAS); (3)
      determination of the COD or oxygen required for complete chemical oxidation of a
      water sample. Portland cement (20%) blended with Depocrete SM/2 (3%) acted as an
      effective stabiliser for residues containing heavy metals as it increased the
      ecotoxicity index (EC50) by more than five times. Thus the heavy metal
      concentration in the leaching liquid was lowered to less than 0.1 mg l-1. The
      addition of 5% of lime afforded a residue easily transportable from the place of
      treatment to the landfill. The precision of the method was studied in terms of
      both repeatability and reproducibility. The values found with respect to EC50 and
      expressed as the relative standard deviation (RSD) were 1.6% and 5.1%,
      respectively.

PMID- 11529191
TI  - Detection of chlorophenolics in effluents from bleaching processes of rice-straw
      pulp.
AB  - A number of chlorinated derivatives of phenols, catechols, guaiacols,
      syringaldehydes, have been detected and their concentrations estimated, using gas
      chromatography in the chlorination (C) and extraction (E) stage of spent bleach
      liquor generated in the laboratory by bleaching rice-straw soda pulp. The
      concentration of various compounds detected have also been compared with their
      reported 96LC50 values.

PMID- 11529192
TI  - Sound science or sound bytes? Europe's struggle with genetically modified crops.
AB  - To restore its authority in the GM debate science has to face up to uncertainty,
      public mistrust and fierce commercial pressures.

PMID- 11529193
TI  - Retrospective evaluation on the surgical treatment of jaw bones ameloblastic
      lesions. Experience with 20 clinical cases.
AB  - BACKGROUND: Ameloblastoma is a benign but locally aggressive neoplasm of the
      odontogenic epithelium that causes expansion of the bone and tends to recur. The
      aim of this article is to present a retrospective evaluation on the management of
      ameloblastic lesion of the jawbones and to compare them with those reported in
      literature in order to rule out which surgical approach is likely to be the most
      appropriate, considering it extremely controversial. METHODS: Data corresponding
      to 20 patients with ameloblastic lesions involving the maxillary bones, admitted
      to the O ral and MaxilloFacial Surgery Department of Verona University Hospital,
      were analyzed in the period between 1984 and 1999. All data were selected for
      sex, age, site of involvement, histological patterns of the lesions, surgical
      steps performed concerning both primary pathology and secondary relapses
      including the reconstructive methods employed. RESULTS: The results showed a
      male/female ratio of 1.5/1. All the affected patients showed endosseous tumour
      masses localized in 90% of the cases at the mandible and only in 10% at the
      maxillary bone. Only one case with soft tissue involvement was observed.
      Treatment was enucleation and bone courettage in the 65% of cases while in 35%
      the lesion was excised performing wide bone resection. The histopathological
      study on the surgical specimens revealed the 50% of the lesions were unicystic
      45% were multicystic showing the other 5% a carcinomatous ameloblastic patterns.
      The recurrence rate in patients managed with enucleation and courettage was
      28.57% while in wide bone resection none recurrence was observed. CONCLUSIONS:
      Simply enucleation and curettage of multicystic ameloblastic lesion of jawbones
      results in an unacceptable recurrence rate. Conservative surgical treatment
      should be considered only in presence of unicystic lesion when extraosseous
      spread has not occurred. Multicystic lesions should be treated with an extended
      surgical resection.

PMID- 11529194
TI  - Ads may raise infection rate.

PMID- 11529195
TI  - Once-a-day indinavir studied.

PMID- 11529196
TI  - Marijuana can be prescribed.

PMID- 11529197
TI  - Trials begin for hepatitis C drug.

PMID- 11529198
TI  - Herpes vaccine encouraging.

PMID- 11529199
TI  - African-American men hide bisexuality.

PMID- 11529200
TI  - Statement by Wolf-Michael Catenhusen, Parliamentary State Secretary at the
      Federal Ministry of Education and Research on the occasion of the Symposium on
      the Future of Molecular Medicine on the topic of "The European Position on
      Embryonic Stem Cells" at the MDC in Berlin on 10 May 2000.

PMID- 11529201
TI  - Regulatory control and standardization of allergenic extracts. Proceedings of the
      9th International Paul-Ehrich-Seminar. September 9-11, 1999. Langen, Germany.

PMID- 11529202
TI  - Summaries for patients. Kidney disease in patients with lupus who are treated
      with potent drugs that suppress the immune system.

PMID- 11529203
TI  - Summaries for patients. Food poisoning from alfalfa and clover sprouts.

PMID- 11529204
TI  - Summaries for patients. The effects of hormone replacement therapy on blood
      pressure in postmenopausal women.

PMID- 11529205
TI  - Summaries for patients. Factors associated with normal blood pressure after
      surgery to treat primary aldosteronism.

PMID- 11529206
TI  - Correction: examination and refractive management of patients with Nystagmus.

PMID- 11529207
TI  - High-resolution footprinting studies of drug-DNA complexes using chemical and
      enzymatic probes.

PMID- 11529208
TI  - One-time screening for colorectal cancer with combined fecal occult-blood testing
      and examination of the distal colon.
AB  - BACKGROUND: Fecal occult-blood testing and sigmoidoscopy have been recommended
      for screening for colorectal cancer, but the sensitivity of such combined testing
      for detecting neoplasia is uncertain. At 13 Veterans Affairs medical centers, we
      performed colonoscopy to determine the prevalence of neoplasia and the
      sensitivity of one-time screening with a fecal occult-blood test plus
      sigmoidoscopy. METHODS: Asymptomatic subjects (age range, 50 to 75 years)
      provided stool specimens on cards from three consecutive days for fecal occult
      blood testing, which were rehydrated for interpretation. They then underwent
      colonoscopy. Sigmoidoscopy was defined in this study as examination of the rectum
      and sigmoid colon during colonoscopy, and sensitivity was estimated by
      determining how many patients with advanced neoplasia had an adenoma in the
      rectum or sigmoid colon. Advanced colonic neoplasia was defined as an adenoma 10
      mm or more in diameter, a villous adenoma, an adenoma with high-grade dysplasia,
      or invasive cancer. Classification of subjects according to the findings was
      based on the most advanced lesion. RESULTS: A total of 2885 subjects returned the
      three specimen cards for fecal occult-blood testing and underwent a complete
      colonoscopic examination. A total of 23.9 percent of subjects with advanced
      neoplasia had a positive test for fecal occult blood. As compared with subjects
      who had a negative test for fecal occult blood, the relative risk of advanced
      neoplasia in subjects who had a positive test was 3.47 (95 percent confidence
      interval, 2.76 to 4.35). Sigmoidoscopy identified 70.3 percent of all subjects
      with advanced neoplasia. Combined one-time screening with a fecal occult-blood
      test and sigmoidoscopy identified 75.8 percent of subjects with advanced
      neoplasia. CONCLUSIONS: One-time screening with both a fecal occult-blood test
      with rehydration and sigmoidoscopy fails to detect advanced colonic neoplasia in
      24 percent of subjects with the condition.

PMID- 11529209
TI  - Use of copper intrauterine devices and the risk of tubal infertility among
      nulligravid women.
AB  - BACKGROUND: Previous studies of intrauterine devices (IUDs), many of which are no
      longer in use, suggested that they might cause tubal infertility. The concern
      that IUDs that contain copper--currently the most commonly used type--may
      increase the risk of infertility in nulligravid women has limited the use of this
      highly effective method of birth control. METHODS: We conducted a case-control
      study of 1895 women recruited between 1997 and 1999. We enrolled 358 women with
      primary infertility who had tubal occlusion documented by hysterosalpingography,
      as well as 953 women with primary infertility who did not have tubal occlusion
      (infertile controls) and 584 primigravid women (pregnant controls). We collected
      information on the women's past use of contraceptives, including copper IUDs,
      previous sexual relationships, and history of genital tract infections. Each
      woman's blood was tested for antibodies to Chlamydia trachomatis. We used
      stratified analyses and logistic regression to assess the association between the
      previous use of a copper IUD and tubal occlusion. RESULTS: In analyses involving
      the women with tubal occlusion and the infertile controls, the odds ratio for
      tubal occlusion associated with the previous use of a copper IUD was 1.0 (95
      percent confidence interval, 0.6 to 1.7). When the primigravid women served as
      the controls, the corresponding odds ratio was 0.9 (95 percent confidence
      interval, 0.5 to 1.6). Tubal infertility was not associated with the duration of
      IUD use, the reason for the removal of the IUD, or the presence or absence of
      gynecologic problems related to its use. The presence of antibodies to chlamydia
      was associated with infertility. CONCLUSIONS: The previous use of a copper IUD is
      not associated with an increased risk of tubal occlusion among nulligravid women
      whereas infection with C. trachomatis is.

PMID- 11529210
TI  - Effect of prone positioning on the survival of patients with acute respiratory
      failure.
AB  - BACKGROUND: Although placing patients with acute respiratory failure in a prone
      (face down) position improves their oxygenation 60 to 70 percent of the time, the
      effect on survival is not known. METHODS: In a multicenter, randomized trial, we
      compared conventional treatment (in the supine position) of patients with acute
      lung injury or the acute respiratory distress syndrome with a predefined strategy
      of placing patients in a prone position for six or more hours daily for 10 days.
      We enrolled 304 patients, 152 in each group. RESULTS: The mortality rate was 23.0
      percent during the 10-day study period, 49.3 percent at the time of discharge
      from the intensive care unit, and 60.5 percent at 6 months. The relative risk of
      death in the prone group as compared with the supine group was 0.84 at the end of
      the study period (95 percent confidence interval, 0.56 to 1.27), 1.05 at the time
      of discharge from the intensive care unit (95 percent confidence interval, 0.84
      to 1.32), and 1.06 at six months (95 percent confidence interval, 0.88 to 1.28).
      During the study period the mean (+/-SD) increase in the ratio of the partial
      pressure of arterial oxygen to the fraction of inspired oxygen, measured each
      morning while patients were supine, was greater in the prone than the supine
      group (63.0+/-66.8 vs. 44.6+/-68.2, P=0.02). The incidence of complications
      related to positioning (such as pressure sores and accidental extubation) was
      similar in the two groups. CONCLUSIONS: Although placing patients with acute
      respiratory failure in a prone position improves their oxygenation, it does not
      improve survival.

PMID- 11529211
TI  - Prognostic importance of elevated jugular venous pressure and a third heart sound
      in patients with heart failure.
AB  - BACKGROUND: The independent prognostic value of elevated jugular venous pressure
      or a third heart sound in patients with heart failure is not well established.
      METHODS: We performed a retrospective analysis of the Studies of Left Ventricular
      Dysfunction treatment trial, in which 2569 patients with symptomatic heart
      failure or a history of it were randomly assigned to receive enalapril or
      placebo. The mean (+/-SD) follow-up was 32+/-15 months. The presence of elevated
      jugular venous pressure or a third heart sound was ascertained by physical
      examination on entry into the trial. The risks of hospitalization for heart
      failure and progression of heart failure as defined by death from pump failure
      and the composite end point of death or hospitalization for heart failure were
      compared in patients with these findings on physical examination and patients
      without these findings. RESULTS: Data on 2479 patients were complete and
      analyzed. In multivariate analyses that were adjusted for other markers of the
      severity of heart failure, elevated jugular venous pressure was associated with
      an increased risk of hospitalization for heart failure (relative risk, 1.32; 95
      percent confidence interval, 1.08 to 1.62; P<0.01), death or hospitalization for
      heart failure (relative risk, 1.30; 95 percent confidence interval, 1.11 to 1.53;
      P<0.005), and death from pump failure (relative risk, 1.37; 95 percent confidence
      interval, 1.07 to 1.75; P<0.05). The presence of a third heart sound was
      associated with similarly increased risks of these outcomes. CONCLUSIONS: In
      patients with heart failure, elevated jugular venous pressure and a third heart
      sound are each independently associated with adverse outcomes, including
      progression of heart failure. Clinical assessment for these findings is currently
      feasible and clinically meaningful.

PMID- 11529212
TI  - Human infection due to recombinant vaccinia-rabies glycoprotein virus.

PMID- 11529213
TI  - Images in clinical medicine. Carotid-body tumor.

PMID- 11529214
TI  - The pathogenesis of vasodilatory shock.

PMID- 11529215
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 26-2001. Hypertensive encephalopathy with impaired renal function
      in a 67-year-old woman with polymyositis.

PMID- 11529216
TI  - Screening for colon cancer--can we afford colonoscopy?

PMID- 11529217
TI  - Time to pardon the IUD?

PMID- 11529218
TI  - The acute respiratory distress syndrome, mechanical ventilation, and the prone
      position.

PMID- 11529219
TI  - The jugular venous pulse and third heart sound in patients with heart failure.

PMID- 11529220
TI  - The diagnosis of brain death.

PMID- 11529221
TI  - The diagnosis of brain death.

PMID- 11529222
TI  - The diagnosis of brain death.

PMID- 11529223
TI  - The diagnosis of brain death.

PMID- 11529224
TI  - The diagnosis of brain death.

PMID- 11529225
TI  - Cutaneous reactions to STI571.

PMID- 11529226
TI  - Heparin-induced thrombocytopenia.

PMID- 11529227
TI  - Heparin-induced thrombocytopenia.

PMID- 11529229
TI  - Atrial fibrillation.

PMID- 11529228
TI  - Atrial fibrillation.

PMID- 11529230
TI  - Treatment of brain metastases of malignant melanoma with temozolomide.

PMID- 11529231
TI  - Acquired type I von Willebrand's disease associated with highly substituted
      hydroxyethyl starch.

PMID- 11529234
TI  - Cancer risk from exposure to occupational acrylamide.

PMID- 11529235
TI  - Dose-response relation between acrylamide and pancreatic cancer.

PMID- 11529236
TI  - Amyotrophic lateral sclerosis and occupational exposure to 2,4
      dichlorophenoxyacetic acid.

PMID- 11529237
TI  - Bullying in hospitals.

PMID- 11529238
TI  - Endoanal advancement flap repair for complex anorectal fistulas.

PMID- 11529239
TI  - Clostridium septicum infection of the aorta.

PMID- 11529240
TI  - The diversity of organelle protein import mechanisms.
AB  - It was once believed that common mechanisms underpin the transfer of proteins
      across the membrane systems of organelles such as mitochondria, chloroplasts and
      peroxisomes. Now that many of the core components of the translocases have been
      indentified, results discussed at a recent conference [Max-Delbruck-Centrum
      Symposium "Protein Transport and Stability"; Berlin, Germany; 21-26 March 2001.
      Organized by Thomas Sommer and Enno Hartmann.] stress just how diverse the
      mechanisms of transport into these organelles really are.

PMID- 11529241
TI  - From the Centers for Disease Control and Prevention. West Nile virus activity-
      Eastern United States, 2001.

PMID- 11529243
TI  - From the Centers for Disease Control and Prevention. Hantavirus pulmonary
      syndrome--Vermont, 2000.

PMID- 11529242
TI  - From the Centers for Disease Control and Prevention. Heat-related deaths--Los
      Angeles County, California, 1999-2000, and United States, 1979-1998.

PMID- 11529244
TI  - From the Centers for Disease Control and Prevention. Drowning--Louisiana, 1998.

PMID- 11529245
TI  - JAMA patient page. Leukemia.

PMID- 11529246
TI  - Subthalamic GAD gene transfer in Parkinson disease patients who are candidates
      for deep brain stimulation.
AB  - This gene transfer experiment is the first Parkinson's Disease (PD) protocol to
      be submitted to the Recombinant DNA Advisory Committee. The principal
      investigators have uniquely focused their careers on both pre-clinical work on
      gene transfer in the brain and clinical expertise in management and surgical
      treatment of patients with PD. They have extensively used rodent models of PD for
      proof-of-principle experiments on the utility of different vector systems. PD is
      an excellent target for gene therapy, because it is a complex acquired disease of
      unknown etiology (apart from some rare familial cases) yet it is characterized by
      a specific neuroanatomical pathology, the degeneration of dopamine neurons of the
      substantia nigra (SN) with loss of dopamine input to the striatum. This pathology
      results in focal changes in the function of several deep brain nuclei, which have
      been well-characterized in humans and animal models and which account for many of
      the motor symptoms of PD. Our original approaches, largely to validate in vivo
      gene transfer in the brain, were designed to facilitate dopamine transmission in
      the striatum using an AAV vector expressing dopamine-synthetic enzymes. Although
      these confirmed the safety and potential efficacy of AAV, complex patient
      responses to dopamine augmenting medication as well as poor results and
      complications of human transplant studies suggested that this would be a
      difficult and potentially dangerous clinical strategy using current approaches.
      Subsequently, we and others investigated the use of growth factors, including
      GDNF. These showed some encouraging effects on dopamine neuron survival and
      regeneration in both rodent and primate models; however, uncertain consequences
      of long-term growth factor expression and question regarding timing of therapy in
      the disease course must be resolved before any clinical study can be
      contemplated. We now propose to infuse into the subthalamic nucleus (STN)
      recombinant AAV vectors expressing the two isoforms of the enzyme glutamic acid
      decarboxylase (GAD-65 and GAD-67), which synthesizes the major inhibitory
      neurotransmitter in the brain, GABA. The STN is a very small nucleus (140 cubic
      mm or 0.02% of the total brain volume, consisting of approximately 300,000
      neurons) which is disinhibited in PD, leading to pathological excitation of its
      targets, the internal segment of the globus pallidus (GPi) and substantia nigra
      pars reticulata (SNpr). Increased GPi/SNpr outflow is believed responsible for
      many of the cardinal symptoms of PD, i.e., tremor, rigidity, bradykinesia, and
      gait disturbance. A large amount of data based on lesioning, electrical
      stimulation, and local drug infusion studies with GABA-agonists in human PD
      patients have reinforced this circuit model of PD and the central role of the
      STN. Moreover, the closest conventional surgical intervention to our proposal,
      deep brain stimulation (DBS) of the STN, has shown remarkable efficacy in even
      late stage PD, unlike the early failures associated with recombinant GDNF
      infusion or cell transplantation approaches in PD. We believe that our gene
      transfer strategy will not only palliate symptoms by inhibiting STN activity, as
      with DBS, but we also have evidence that the vector converts excitatory STN
      projections to inhibitory projections. This additional dampening of outflow
      GPi/SNpr outflow may provide an additional advantage over DBS. Moreover, of
      perhaps the greatest interest, our preclinical data suggests that this strategy
      may also be neuroprotective, so this therapy may slow the degeneration of
      dopaminergic neurons. We will use both GAD isoforms since both are typically
      expressed in inhibitory neurons in the brain, and our data suggest that the
      combination of both isoforms is likely to be most beneficial. Our preclinical
      data includes three model systems: (1) old, chronically lesioned parkinsonian
      rats in which intraSTN GAD gene transfer results not only in improvement in both
      drug-induced asymmetrical behavior (apomorphine symmetrical rotations), but also
      in spontaneous behaviors. In our second model, GAD gene transfer precedes the
      generation of a dopamine lesion. Here GAD gene transfer showed remarkable
      neuroprotection. Finally, we carried out a study where GAD-65 and GAD-67 were
      used separately in monkeys that were resistant to MPTP lesioning and hence showed
      minimal symptomatology. Nevertheless GAD gene transfer showed no adverse effects
      and small improvements in both Parkinson rating scales and activity measures were
      obtained. In the proposed clinical trial, all patients will have met criteria for
      and will have given consent for STN DBS elective surgery. Twenty patients will
      all receive DBS electrodes, but in addition they will be randomized into two
      groups, to receive either a solution containing rAAV-GAD, or a solution which
      consists just of the vector vehicle, physiological saline. Patients, care
      providers, and physicians will be blind as to which solution any one patient
      receives. All patients, regardless of group, will agree to not have the DBS
      activated until the completion and unblinding of the study. Patients will be
      assessed with a core clinical assessment program modeled on the CAPSIT, and in
      addition will also undergo a preop and several postop PET scans. At the
      conclusion of the study, if any patient with sufficient symptomatic improvement
      will be offered DBS removal if they so desire. Any patients with no benefit will
      simply have their stimulators activated, which would normally be appropriate
      therapy for them and which requires no additional operations. If any unforeseen
      symptoms occur from STN production of GABA, this might be controlled by blocking
      STN GABA release with DBS, or STN lesioning could be performed using the DBS
      electrode. Again, this treatment would not subject the patient to additional
      invasive brain surgery. The trial described here reflects an evolution in our
      thinking about the best strategy to make a positive impact in Parkinson Disease
      by minimizing risk and maximizing potential benefit. To our knowledge, this
      proposal represents the first truly blinded, completely controlled gene or cell
      therapy study in the brain, which still provides the patient with the same
      surgical procedure which they would normally receive and should not subject the
      patient to additional surgical procedures regardless of the success or failure of
      the study. This study first and foremost aims to maximally serve the safety
      interests of the individual patient while simultaneously serving the public
      interest in rigorously determining in a scientific fashion if gene therapy can be
      effective to any degree in treating Parkinson's disease.

PMID- 11529247
TI  - A phase I/II dose escalation and activity study of intravenous injections of
      OCaP1 for subjects with refractory osteosarcoma metastatic to lung.
AB  - Osteosarcomas are malignant tumors arising from skeletal tissue and occur most
      frequently during childhood and adolescence. Osteosarcoma was once fatal in more
      than 80% of patients who presented with apparently localized disease.
      Chemotherapy, better surgical techniques, and improved staging methods now allow
      most patients to be treated with limb-sparing surgery and to be cured of their
      disease. However, many patients still die of metastatic disease and new
      approaches are still needed. The lung is the most frequent metastatic site and is
      treated with chemotherapy and surgical resections. Multiple resections for
      repeated recurrences that are limited to the lung are not uncommon but are
      limited by the amount of lung tissue that can be removed and become futile as
      recurrences become more frequent. Although a main component of initial therapy,
      chemotherapy has not been shown to be of benefit for recurrent disease. Direct
      introduction of therapeutic genes into malignant cells in vivo may provide
      effective treatment of solid tumors. The proposed study will use the adenoviral
      vector Ad-OC-E1a (OCaP1), which contains a murine osteocalcin (OC) promoter to
      regulate the production of the adenoviral E1a protein to allow for restricted
      viral replication and subsequent lysis of tumor cells. The OC promoter is
      developmentally regulated, with peak expression in the neonate. It functions
      primarily in osteoblasts found in growing bone and is highly expressed in
      osteogenic sarcomas. Because adenovirus is quickly cleared by normal tissues,
      especially the liver, systemic administration has been problematic. Although
      bioavailability would be decreased following exposure to the liver, the OcaP1
      construct should not be hepatotoxic due to OC-restricted tissue expression of the
      Ela protein. Metastatic disease to the lung is a major problem and often is the
      cause of death for patients with osteogenic sarcoma. Treatment of pulmonary
      metastases could potentially be accomplished using intravenously administered
      OcaP1 since the material would pass through the lung prior to reaching the
      systemic circulation. In animal models using OC expressing tumors, OCaP1 has been
      effective at reducing lung metastases following intravenous injection. This
      protocol is a phase I/II investigational study of bolus intravenous injections of
      Ad-OC-E1a for the treatment of chemotherapy-refractory osteogenic sarcoma that
      has metastasized to the lungs. Initially patients will receive one injection of 1
      x 10(10), 1 X 10(11), 1 X 10(12), or 5 x 10(12) viral particles of Ad-OC-E1a
      using a standard Phase I dose escalation design that studies 3 to 6 patients per
      dose group. After safety has been established in the first part of the trial, we
      will evaluate the anti-tumor activity of OCaP1. Because the matrix associated
      with osteogenic sarcoma may not change despite tumor necrosis, radiographic
      evaluation alone has not been considered sufficient to evaluate response in this
      disease. Histologic criteria that assess the amount of necrosis have been shown
      to have prognostic significance and are a key component of the anti-tumor
      response assessment. Therefore, the anti-tumor assessments will be carried out in
      patients for whom resection of their pulmonary metastases is clinically
      indicated. These patients will receive one injection of OCaP1 and 28 to 42 days
      later undergo their planned pulmonary resection. Responses will be graded using
      radiographic and histologic objective response criteria that are considered
      standard for osteogenic sarcoma. A total of 14 to 25 patients, depending upon
      whether objective anti-tumor responses occur, will be studied in this part of the
      protocol.

PMID- 11529248
TI  - VEGF gene transfer for diabetic neuropathy.
AB  - Among diabetics, peripheral neuropathy is common and ultimately accounts for
      significant morbidity. The ultimate consequence of such sensory defects involving
      the lower extremities may be foot ulceration initiated by trauma that is
      inapparent to the patient. Such ulcerations often lead to lower extremity
      amputation, a complication that is 15 times higher in diabetic versus non
      diabetic patients. Preliminary clinical studies have demonstrated improvement in
      signs and symptoms of sensory neuropathy in patients with lower extremity
      vascular occlusive disease following intramuscular injection of naked DNA
      encoding vascular endothelial growth factor (VEGF). To determine if such a
      strategy could be applied to diabetic patients, including those without evidence
      of large vessel occlusive disease, we investigated the hypothesis that
      experimental diabetic neuropathy results from destruction of the vasa nervorum
      and can be reversed by administration of an angiogenic growth factor. In two
      different animal models of diabetics, nerve blood flow and the number of vasa
      nervorum were found to be markedly attenuated resulting in severe peripheral
      neuropathy. In contrast, following VEGF gene transfer, vascularity and blood flow
      in nerves of treated animals were similar to those of non-diabetic controls;
      constitutive overexpression of VEGF resulted in restoration of large and small
      fiber peripheral nerve function. These findings implicate microvascular
      disruption as the basis for diabetic neuropathy and suggest that angiogenic
      growth factors may constitute a novel treatment strategy for this pernicious
      disorder. Accordingly, we now seek to address the following two objectives: 1.
      Objective #1: is to evaluate the safety and impact of phVEGF165 gene transfer on
      sensory neuropathy in patients with diabetes and associated macrovascular disease
      involving the lower extremities. 2. Objective #2: is to evaluate the safety and
      impact of phVEGF165 gene transfer on sensory neuropathy in patients with diabetes
      without macrovascular disease involving the lower extremities. The protocol
      outlined in this Investigational New Drug Application has been designed as a
      Phase I/II, single-site, dose escalating, double-blind, placebo controlled study
      to evaluate the safety and impact of phVEGF165 gene transfer on sensory
      neuropathy in patients with diabetes with or without macrovascular disease
      involving the lower extremities. Diabetic males or females > 21 years old with
      sensory neuropathy with or without macrovascular disease will be eligible. A
      total of 192 patients will be recruited into two arms of the study (each arm
      consisting of 96 patients) over a period of 4 years (the fifth year will be
      limited to follow-up examinations). The 96 patients in each of the two arms of
      the study will comprise 3 cohorts, each consisting of 32 patients. Within each of
      these cohorts, patients will be randomized to receive phVEGF165 or placebo based
      upon a 3:1 randomization ratio. Thus, at the completion of the study, 24 patients
      will have each received a given dose (1, 2, or 4 mg phVEGF165) and 24 patients
      will have received placebo. Doses will be employed in a serial dose-escalating
      fashion. The entire volume of the study drug will be divided and delivered in 8
      intramuscular injections administered into the foot, calf muscle, or distal thigh
      muscle of the affected extremity. Following the initial set of injections, repeat
      treatment with an identical dose will be provided 2 and 4 weeks after initial
      treatment.

PMID- 11529250
TI  - Exemption from RAC review of certain types of human gene transfer vaccine
      protocols: interpretation of the term "persistence of the vector encoded
      immunogen".

PMID- 11529249
TI  - A phase I trial of genetically modified Salmonella typhimurium expressing
      cytosine deaminase (TAPET-CD, VNP20029) administered by intratumoral injection in
      combination with 5-fluorocytosine for patients with advanced or metastatic
      cancer. Protocol no: CL-017. Version: April 9, 2001.
AB  - An attenuated strain of Salmonella typhimurium, designated VNP20009, was
      generated by deletion of the msbB and purl genes. When VNP20009 was administered
      intravenously (IV) to mice bearing spontaneous, syngeneic, or human xenograft
      tumors, the bacteria accumulated preferentially within the extracellular
      components of tumors, forming tumor-to-normal tissue ratios exceeding 300-1000 to
      1. NVP20009 was administered safely at doses up to 2.5 x 10(9) cfu/kg in monkey
      toxicology studies. Based on the preclinical data, VNP20009 entered Phase I human
      clinical trials in November 1999, and has now been administered to >45 patients
      by IV or direct intratumoral injection. By the intratumoral route, a maximum
      tolerated dose has not been reached, and dose escalation continues past the
      current dose level of 4 x 10(7)/m2. Furthermore, VNP20009 persisted in injected
      tumors for at least 2 weeks in 8/11 patients treated to date. By 30-min IV
      administration, a maximum tolerated dose (MTD) of 3 X 10(8) cfu/m2 has been
      established. In all patients treated to date, VNP20009 was not shed in urine or
      stool. VNP20009 has been further modified by chromosomal insertion of an E. coli
      cytosine deaminase (CD) gene at the deltamsbB locus which, when expressed,
      converts 5-fluorocytosine (5-FC) to 5-fluorouracil (5-FU). The CD containing
      VNP20009 was designated TAPET-CD or VNP20029. TAPET-CD had similar efficacy and
      safety in murine tumor models and similar safety profiles in animal toxicology
      studies, compared to its parent VNP20009. Specifically, TAPET-CD had a reduced
      virulence of >10,000 fold, when compared to the wild-type Salmonella strain. It
      was well-tolerated at doses up to 2 x 10(6) cfu/mouse and 1 X 10(10) cfu/monkey.
      After an IV or direct tumor injection to tumor-bearing mice, TAPET-CD reached
      tumor levels as high as 10(8)-10(9) cfu/gm. When compared to the accumulation in
      liver or spleen, the normal tissues with the greatest colonization of TAPET-CD,
      tumor-to-normal tissue ratios of TAPET-CD were 300-1000 to 1. TAPET-CD also
      caused tumor growth inhibition of >90% in several murine tumor models. When 5-FC
      was administered by intraperitoneal (IP) injection once or 3 times daily to tumor
      bearing mice that had been pre-treated with TAPET-CD, high levels of 5-FU
      (reaching 20-40 microM/g) were detected in the tumor, with low or undetectable 5
      FU levels in normal tissues (e.g., spleen, liver, etc.). Furthermore, co
      administration of 5-FC and TAPET-CD in 4 different murine tumor models enhanced
      anti-tumor activity compared to the significant anti-tumor activity of TAPET-CD
      alone, further confirming the benefit of the inserted CD gene. On the basis of
      the preclinical data, a Phase I clinical protocol is proposed in which advanced
      cancer patients will receive TAPET-CD by direct intratumoral injection and 5-FC.
      TAPET-CD will be administered on day 1. 5-FC will be given orally q8h daily
      beginning day 4 or when all toxicities of TAPET-CD have resolved to < or = grade
      1, and continued for 14 days. Tumor tissues will be sampled to verify TAPET-CD
      colonization and to measure intratumoral 5-FC and 5-FU concentrations on day 8. A
      second sample of tumor tissue will be obtained between day 15-17 in selected
      patients to confirm the persistence of high levels of bacteria in tumor and to
      obtain a second measurement of 5-FC and 5-FU intra-tumoral concentrations. The
      TAPET-CD/5-FC treatment cycle will be repeated in appropriate patients on day 29.

PMID- 11529251
TI  - Rates of verbal fluency decline in the longitudinal assessment of Alzheimer's
      disease.

PMID- 11529252
TI  - Acute life-threatening toxicity of cancer treatment.
AB  - Although patients with cancer may derive much benefit from treatment, they are at
      risk for developing life-threatening complications. Hypersensitivity reactions
      can be severe, as in the case of anaphylaxis with L-asparaginase. Cardiac
      toxicities consist of arrhythmias with various drugs, hemorrhagic myocarditis
      with cyclophosphamide and ifosfamide, cardiomyopathy with anthracyclines, and
      pericardial disease. Acute respiratory failure may occur as a result of ARDS
      caused by ATRA or cytarabine, from interstitial fibrosis, or from pulmonary veno
      occlusive disease. Hemorrhagic cystitis caused by cyclophosphamide and ifosfamide
      can be severe and result in exsanguination if unresponsive to treatment.
      Disseminated intravascular coagulation and thrombotic microangiopathy can produce
      thrombotic or hemorrhagic complications. Gastrointestinal toxicities include
      significant hepatotoxicity with a variety of drugs and development of acute
      surgical abdomen.

PMID- 11529253
TI  - Reduction of thrombogenic potential by physical exercise in the elderly.

PMID- 11529254
TI  - [Is ambulatory blood pressure monitoring reliable in hypertensive patients with
      atrial fibrillation?].
AB  - Atrial fibrillation (AF) is commonly seen in patients (pts) with systemic
      hypertension. They are usually excluded from ambulatory blood pressure monitoring
      (ABPM) because its accuracy is unknown. The aim of our study was to determine if
      ABPM can be used to assess 24 hour BP in pts with AF. We included hypertensive
      pts with chronic (> 6 months) AF, controlled heart rate (60-100 c.p.m), under
      therapy and also hypertensive pts in sinus rhythm (control group--CG). They were
      submitted to 24 hour ABPM (Spacelabs 90207). Manual BP with a standard mercury
      sphygmomanometer was taken during 3 visits (office BP) and on the day of
      ambulatory monitoring. Simultaneous measurements with a T-Tube were also
      performed. Thirty pts with chronic AF (63% males), mean age 73 +/- 8 years (52
      85) and 18 pts in sinus rhythm (CG) were studied. The age, gender, office BP,
      ambulatory BP and proportion of successful measurements was similar in the 2
      groups. In CG systolic and diastolic office BP did not differ from day ambulatory
      BP (148 +/- 14/84 +/- 7 vs 138 +/- 18/76 +/- 11 mmHg) and the same was seen in
      pts in AF (table). In this group, only the systolic BP taken immediately before
      the ambulatory device was put on, was significantly different from day ambulatory
      BP (148 +/- 21 vs 137 +/- 19 mmHg, p = 0.04). The proportion of successful
      measurements in AF group was 94 +/- 8 (65-98) with 93% > 80%. In 64 simultaneous
      measurements the differences were 6 +/- 5 and 5 +/- 5 mmHg for systolic and
      diastolic BP. Casual and ambulatory heart rate was also similar in the two groups
      (76 +/- 7/76 +/- 12--AF group; 78 +/- 10/78 +/- 8--control group). In conclusion,
      this study demonstrates that ABPM can be used to assess BP in patients with
      atrial fibrillation. There was a high percentage of successful recordings (93%).
      As in patients in sinus rhythm, there was no significantly difference in mean
      office blood pressure and daytime ambulatory blood pressure.

PMID- 11529255
TI  - Pharmacological approaches to inhibit endogenous glucose production as a means of
      anti-diabetic therapy.
AB  - The inappropriate overproduction of glucose by the liver is one of the key
      contributors to the hyperglycaemia of the diabetic state, and thus is a logical
      site of intervention for novel anti-diabetic approaches. Metformin is the only
      currently marketed anti-hyperglycaemic drug whose action is attributed largely to
      its having inhibitory effects on hepatic glucose production, but its molecular
      site and mechanism(s) of action remain unknown, whereas the liver acting PPAR
      alpha agonists have their effects primarily on lipid metabolism. This review
      therefore rather focuses on candidate molecular targets within the liver for anti
      hyperglycaemic therapy, and describes potential rate-controlling receptors and
      enzymes within the glucose producing pathways (glycogenolysis and
      gluconeogenesis). Most focus is directed towards inhibitors of the enzymes
      glucose-6-phosphatase, fructose-1,6-bisphosphatase and glycogen phosphorylase,
      and towards glucagon receptor antagonists, as these appear to be the most
      advanced in preclinical and clinical development, although progress with other
      potential targets is also described. Evidence of the anti-diabetic potential of
      such agents from animal studies is presented, and the relative merits of each
      approach are reviewed and compared. It is likely that such agents will become
      important additions to the therapeutic approaches to combat diabetes.

PMID- 11529256
TI  - A 76-year-old woman with polymyalgia, polyarthralgia, and interstitial lung
      disease.

PMID- 11529257
TI  - Primary prevention of lead poisoning in children.

PMID- 11529258
TI  - Depression and heart disease.

PMID- 11529259
TI  - COPD: management of acute exacerbations and chronic stable disease.
AB  - Acute exacerbations of chronic obstructive pulmonary disease (COPD) are treated
      with oxygen (in hypoxemic patients), inhaled beta2 agonists, inhaled
      anticholinergics, antibiotics and systemic corticosteroids. Methylxanthine
      therapy may be considered in patients who do not respond to other
      bronchodilators. Antibiotic therapy is directed at the most common pathogens,
      including Streptococcus pneumoniae, Haemophilus influenzae and Moraxella
      catarrhalis. Mild to moderate exacerbations of COPD are usually treated with
      older broad-spectrum antibiotics such as doxycycline, trimethoprim
      sulfamethoxazole and amoxicillin-clavulanate potassium. Treatment with augmented
      penicillins, fluoroquinolones, third-generation cephalosporins or aminoglycosides
      may be considered in patients with more severe exacerbations. The management of
      chronic stable COPD always includes smoking cessation and oxygen therapy. Inhaled
      beta2 agonists, inhaled anticholinergics and systemic corticosteroids provide
      short-term benefits in patients with chronic stable disease. Inhaled
      corticosteroids decrease airway reactivity and reduce the use of health care
      services for management of respiratory symptoms. Preventing acute exacerbations
      helps to reduce long-term complications. Long-term oxygen therapy, regular
      monitoring of pulmonary function and referral for pulmonary rehabilitation are
      often indicated. Influenza and pneumococcal vaccines should be given. Patients
      who do not respond to standard therapies may benefit from surgery.

PMID- 11529260
TI  - Information from your family doctor. Chronic obstructive pulmonary disease.

PMID- 11529261
TI  - Commonly missed diagnoses in the childhood eye examination.
AB  - Early and accurate detection of eye disorders in children can present a challenge
      for family physicians. Visual acuity screening, preferably performed before four
      years of age, is essential for diagnosing amblyopia. Cover testing may disclose
      small-angle or intermittent strabismus. Leukocoria, which is detected with an
      ophthalmoscope, may indicate retinoblastoma or cataract. Children with glaucoma
      may have light sensitivity and enlargement of the cornea, and conjunctivitis that
      does not respond quickly to treatment may reflect more serious ocular
      inflammation. Children with serious eye injuries often present to the primary
      care physician. Nystagmus and many systemic conditions are associated with
      specific eye findings.

PMID- 11529262
TI  - Recognizing spinal cord emergencies.
AB  - Physicians who work in primary care settings and emergency departments frequently
      evaluate patients with neck and back pain. Spinal cord emergencies are uncommon,
      but injury must be recognized early so that the diagnosis can be quickly
      confirmed and treatment can be instituted to possibly prevent permanent loss of
      function. The differential diagnosis includes spinal cord compression secondary
      to vertebral fracture or space-occupying lesion, spinal infection or abscess,
      vascular or hematologic damage, severe disc herniation and spinal stenosis. The
      most important information in the assessment of a possible spinal cord emergency
      comes from the history and the clinical evaluation. Physicians must look for "red
      flags"--key historical and clinical clues that increase the likelihood of a
      serious underlying disorder. In considering diagnostic tests, physicians should
      apply the principles outlined in an algorithm for the evaluation of low back pain
      prepared by the Agency for Healthcare Research and Quality (formerly the Agency
      for Health Care Policy and Research). Computed tomography and magnetic resonance
      imaging can clearly define anatomy, but these studies are costly and have a high
      false-positive rate. Referral of high-risk patients to a neurologist or spine
      specialist may be indicated.

PMID- 11529263
TI  - Assessment and treatment of depression following myocardial infarction.
AB  - Approximately 65 percent of patients with acute myocardial infarction report
      experiencing symptoms of depression. Major depression is present in 15 to 22
      percent of these patients. Depression is an independent risk factor in the
      development of and mortality associated with cardiovascular disease in otherwise
      healthy persons. Persons who are depressed and who have pre-existing
      cardiovascular disease have a 3.5 times greater risk of death than patients who
      are not depressed and have cardiovascular disease. Physicians can assess patients
      for depression by using one of several easily administered and scored self-report
      inventories, including the SIG E CAPS + mood mnemonic. Cognitive-behavior therapy
      is the preferred psychologic treatment. Selective serotonin reuptake inhibitor
      antidepressants are the recommended pharmacologic treatment because of the
      relative absence of effects on the cardiovascular system. The combination of a
      selective serotonin reuptake inhibitor with cognitive-behavior therapy is often
      the most effective treatment for depression in patients with cardiovascular
      disease.

PMID- 11529264
TI  - Information from your family doctor. Depression after heart attack--what should I
      know?

PMID- 11529265
TI  - Principles of appropriate antibiotic use: Part III. Acute rhinosinusitis. Centers
      for Disease Control and Prevention.

PMID- 11529266
TI  - What can the neurobiologist learn from mapping genes linked with behavioral
      traits?

PMID- 11529267
TI  - Chromosomal linkage associated with disease severity in the hydrocephalic H-Tx
      rat.
AB  - Infantile hydrocephalus results in neurological deficits despite surgical
      treatment. Fetal-onset hydrocephalus in humans can be caused by developmental
      abnormalities that are genetic in origin. The H-Tx rat has hydrocephalus with 40%
      penetrance and a polygenic inheritance. A backcross with Fisher F344 inbred
      strain produced a total of 1500 progeny with 17.5% hydrocephalus. Of these, only
      12.3% had overt disease and the remaining 5.2% had mild disease seen only after
      fixation of the brain. Disease severity was measured for all affected rats using
      the ratio of ventricle to brain width. The severity measure confirmed that there
      are two populations, mild hydrocephalus (M; ratio, <0.4) and severe hydrocephalus
      (S; ratio, >0.4), with a small overlap. For genotyping, the two populations were
      each subdivided based on the ratio measure to give a total of four groups of
      increasing severity. After an initial genome scan with microsatellite markers,
      all hydrocephalic rats and a subset of 128 normal progeny were genotyped on
      chromosomes 4, 9, 10, 11, 17 and 19. Rats in the mildest group had association
      with a locus on chromosome 4 (LOD 2.4), whereas those in the severest group were
      associated with a locus on chromosome 17 (LOD 3.2). All except the least affected
      group were associated with a heterozygous genotype on chromosomes 10 and 11 (LOD
      4.5 and 3.5, respectively). Chromosomes 9 and 19 had weak linkage to
      hydrocephalus. The number of hydrocephalus-associated loci carried by each rat
      correlated with the severity of disease. It is concluded that the severity of
      hydrocephalus in H-Tx is influenced by different genetic loci.

PMID- 11529268
TI  - Full-genome scans with autistic disorder: a review.
AB  - Autistic disorder is characterized by severe disturbances of social relatedness,
      impairments in language and communication, and restricted, repetitive, and
      stereotyped patterns of behaviors. Accumulated data strongly support the notion
      that genetic factors, as yet undetermined, play a significant role in the
      etiology of this syndrome. As genetic research in autism is still exploratory,
      full genomewide searches have been performed to localize susceptibility regions
      within the genome. Methods and results from the four first full-genome scans
      published to date (IMGSAC, 1998a; Philippe et al., 1999; Risch et al., 1999d;
      Barrett et al., 1999) are considered in this review. The four sets of multipoint
      linkage results are grouped in a single figure to facilitate comparisons among
      the four studies and with previous or future results. Although findings must be
      considered with caution because LOD score values do not reach the threshold for
      significant linkage, a region of approximately 50 cM on the long arm of
      chromosome 7 appears to play a role in the etiology of autistic disorder.

PMID- 11529269
TI  - Assessing implications between genotypic and phenotypic variables through lattice
      analysis.
AB  - A previous paper assessed a "Molecular Mapping of Twenty-Four Features of Down
      Syndrome on Chromosome 21" (Delabar et al., 1993), by analyzing the
      genotypes/phenotypes of patients suffering from partial trisomy. The mapping was
      defined through implications--each feature was mapped to the conjunction of
      cytogenetic bands that were shared by all patients having that feature. In the
      present paper, we extend that approach to determine how far those implications
      depart from defining equivalences. Finding equivalences is important. Local
      equivalences permit a genetic characterization of a feature. And if global
      equivalences held for all features, that set of bands would be sufficient to
      characterize the various phenotypes observed in individuals with partial trisomy
      21. To extend the earlier approach, we examine the structure of equivalences as
      well as the structure of implications. We examine both conjunctions of bands and
      conjunctions of features. The use of Galois lattices permits simultaneous
      evaluation of both kinds of structures. Each Galois lattice is labeled with a
      basis (minimal generating set) of implications going from conjunctions of
      features into bands and those going from conjunctions of bands into features.
      Analysis reveals that about half of the conjunctions of bands that characterize
      the genetic structure embody equivalences. This allows us to improve the genetic
      description of features and to specify minimal sets of questions that need to be
      investigated to make the global genetic description more precise.

PMID- 11529270
TI  - Quantitative trait locus mapping: fishing strategy or replicable results?
AB  - Genomewide scan, as shown by recently published linkage studies on the behavior
      of mice or in psychiatry, provides evidence for replicated quantitative trait
      loci (QTL). Several studies of Alzheimer's disease have demonstrated the promise
      of moving from clinical diagnoses to biological signs for psychiatric
      investigations. Empirical studies also demonstrate that genetic background,
      differences in environment, epistatic effects, and definition of the phenotype
      (including psychiatric diagnosis) all actively contribute to limit the
      duplication of QTL.

PMID- 11529271
TI  - The genetic architecture of odor-guided behavior in Drosophila melanogaster.
AB  - The avoidance response to repellent odorants in Drosophila melanogaster, a
      response essential for survival, provides an advantageous model for studies on
      the genetic architecture of behavior. Transposon tagging in a highly inbred
      strain of flies in combination with a rapid and simple statistical behavioral
      assay enables the identification of not only large phenotypic effects, but also
      small aberrations from wild-type avoidance behavior. The recent completion of the
      sequence of the Drosophila genome facilitates the molecular characterization of
      transposon-tagged genes and correlation between gene expression and behavior in
      smell-impaired (smi) mutant lines. Quantitative genetic analyses of a collection
      of smi lines in a coisogenic background revealed an extensive network of
      epistatic interactions among genes that shape the olfactory avoidance response.
      The identification and functional characterization of proteins encoded by smi
      genes that form part of the olfactory subgenome and correlation of polymorphisms
      in these genes with variation in odor-guided behavior in natural populations will
      advance our understanding of the genetic architecture of chemosensory behavior.

PMID- 11529272
TI  - Possible causal relationships between cerebellar patterns of foliation and
      hindlimb coordination in laboratory mice: a quantitative trait locus analysis.
AB  - The cerebellum is involved in a large set of integrative functions including
      memory, affect, and motricity. The cerebellar patterns of foliation and their
      causal relationships with motricity were investigated via a wide genome scan
      approach and quantitative trait locus (QTL) strategy. QTLs were mapped in an F2
      population derived from NZB/B1NJ and C57BL/6By inbred strains of mice for
      cerebellar fissures in the four vermal lobules (intraculminate, uvula, declival,
      and intracentral) and for hindpaw slips in a bar crossing test. No linkage was
      detected for uvula and intracentral fissures. We found five QTLs linked to
      declival fissure: Cpfd-1q and Cpfd-2q (chromosome 1), Cpfd-3q (chromosome 5),
      Cpfd-4q (chromosome 9), and Cpfd-5q (chromosome 13). Two QTLs were also mapped
      for intraculminate fissure Cpfi-1q (chromosome 4) and Cpfi-2q (chromosome 1).
      Most of the confidence intervals of these QTLs included genes that were
      previously identified for their implication in the physiological mechanisms
      underlying cerebellar patterns of foliation. Only one significant QTL was found
      for the measure of hindpaw coordination (Tne-1q). It was linked with Cpfd-1q and
      Cpfd-2q on the telomeric part of chromosome 1.

PMID- 11529273
TI  - Identifying genetic influences on sleep: an approach to discovering the
      mechanisms of sleep regulation.
AB  - Comparisons of sleep patterns of various inbred strains of mice have revealed
      differences in daily amounts of slow-wave sleep and rapid-eye movement sleep, in
      circadian patterns of sleep, and in some parameters of the electroencephalograms
      both in healthy mice and in mice undergoing microbial infections. Technical
      considerations will probably be an important variable in achieving consensus
      between different independent studies that use a genetic approach to identify
      sleep-regulatory genes or mechanisms. However, despite such differences, current
      data suggest that both normal sleep and various sleep disorders either have a
      genetic basis or are influenced by genetically determined physiologic or
      environmental predispositions. Excessive sleepiness, abnormal sleep patterns,
      nonrestorative sleep, and fatigue are becoming increasingly pervasive in modern
      society. Identifying genes that influence vigilance may ultimately contribute to
      a better understanding of the processes that control normal sleep and contribute
      to sleep disorders and may eventually promote the development of interventions to
      prevent or alleviate these disabling medical conditions.

PMID- 11529274
TI  - The midbrain dopaminergic system: anatomy and genetic variation in dopamine
      neuron number of inbred mouse strains.
AB  - The mesotelencephalic dopamine system is genetically variable and affects motor
      behavior, motivation, and learning. Here we examine the genetic variation of
      mesencephalic DA neuron number in a quasi-congenic RQI mouse strain and its
      background partner and in a recombinant inbred strain with different levels of
      mesencephalic tyrosine hydroxylase activity (TH/MES). We used B6.Cb4i5
      alpha6/Vad, C57BL/6By, and CXBI, which are known to express high, intermediate,
      and low levels of TH/MES, respectively. Unbiased stereological sampling with
      optical disector counting methods were employed to estimate the number of TH
      positive neurons in the A8-A9-A10 cell groups. Morphometric studies on the
      mesencephalic dopamine cell groups indicated that male mice of the B6.Cb4i5
      alpha6/Vad strain were endowed with a significantly lower number of TH-positive
      cells than CXBI mice. In all strains studied, the right retrorubral field (A8
      area) had a higher number of dopamine neurons compared to the left A8 area. The
      results suggest an inverse relationship between TH/MES and number of dopamine
      neurons in the A9-A10 cell groups and significant lateral asymmetry in the A8
      cell group. A detailed anatomical atlas of the mesencephalic A8-A9-A10
      dopaminergic cell groups in the mouse is also presented to facilitate the
      assignment of TH-positive neurons to specific cell groups.

PMID- 11529275
TI  - QTL analysis and genomewide mutagenesis in mice: complementary genetic approaches
      to the dissection of complex traits.
AB  - Quantitative genetics and quantitative trait locus (QTL) mapping have undergone a
      revolution in the last decade. Progress in the next decade promises to be at
      least as rapid, and strategies for fine-mapping QTLs and identifying underlying
      genes will be radically revised. In this Commentary we address several key
      issues: first, we revisit a perennial challenge--how to identify individual genes
      and allelic variants underlying QTLs. We compare current practice and procedures
      in QTL analysis with novel methods and resources that are just now being
      introduced. We argue that there is no one standard of proof for showing QTL =
      gene; rather, evidence from several sources must be carefully assembled until
      there is only one reasonable conclusion. Second, we compare QTL analysis with
      whole-genome mutagenesis in mice and point out some of the strengths and weakness
      of both of these phenotype-driven methods. Finally, we explore the advantages and
      disadvantages of naturally occurring vs mutagen-induced polymorphisms. We argue
      that these two complementary genetic methods have much to offer in efforts to
      highlight genes and pathways most likely to influence the susceptibility and
      progression of common diseases in human populations.

PMID- 11529276
TI  - Genetic dissection of the olfactory bulbs of mice: QTLs on four chromosomes
      modulate bulb size.
AB  - Olfaction is influenced by a complex mix of environmental and genetic factors
      that modulate the production, migration, and maturation of cells in the olfactory
      bulbs. In this study we analyzed effects of sex, age, body weight, and brain
      weight on olfactory bulb size in sexually mature mice. We then used regression
      corrected values (residuals) to map quantitative trait loci (QTLs) that
      selectively modulate bulb weight. This biometric analysis has relied on an F2
      intercross between C57BL/6J (B6) and DBA/2J (D2) inbred strains and a large
      sample of 35 BXD recombinant inbred (RI) strains. Bilateral bulb weight in adult
      mice ranges from 10 to 30 mg. Half of this remarkable variation can be predicted
      from differences in brain weight, sex, body weight, and age. A 100-mg difference
      in brain weight is associated with a 4.4-mg difference in bulb weight. Bulbs gain
      in weight by 0.2 mg/week--a 1% increase that continues until at least 300 days of
      age. Males tend to have slightly larger bulbs than females. By combining data
      from both related crosses (F2 and RI) we identified four QTLs with selective
      effects on bulb size (genomewide p < .05). Bulb4a is located on chromosome 4 (Chr
      4) and Bulb6a is located on Chr 6. Alleles inherited from B6 at both of these
      loci increase bulb weight by 0.5-1.0 mg. Bulb11a is located on proximal Chr 11
      and Bulb17a is located on the proximal part of Chr 17. In contrast to the first
      two QTLs, B6 alleles at these two loci decrease bulb weight by 0.5-1.0 mg.
      Collectively, the four loci account for 20% of the phenotypic variance in bulb
      weight.

PMID- 11529277
TI  - Further characterization and high-resolution mapping of quantitative trait loci
      for ethanol-induced locomotor activity.
AB  - Differential sensitivity to the stimulant effects of ethanol on locomotor
      activity is determined in part by genetic differences. Among inbred strains of
      mice, moderate doses of ethanol (1-2 g/kg) stimulate locomotor activity in some
      strains, e.g., the DBA/2J (D2), but only mildly affect activity in other strains,
      e.g., C57BL/6J (B6) (Crabbe et al., 1982, 1983; Crabbe, 1986; Dudek and Phillips,
      1990; Dudek et al., 1991; Dudek and Tritto, 1994). Quantitative trait loci (QTL)
      for the acute ethanol (1.5 g/kg) locomotor response has been identified in the
      BXD recombinant inbred (RI) series (N = 25 strains), a C57BL/6J x DBA/2J (B6D2)
      F2 intercross (N = 1800), and heterogeneous stock (HS) mice (N = 550). QTLs
      detected (p < .01) in the RI series were found on chromosomes 1, 2, and 6 and
      these QTLs were expressed in a time-dependent fashion. The QTLs on chromosomes 1
      and 2 were confirmed in the F2 intercross at p < 10(-7) or better. HS mice from
      G32 to G35 were used to fine-map the chromosome 2 QTL. Compared to the consensus
      map, the genetic map in the HS animals was expanded 10- to 15-fold. Over the
      region flanked by D2Mit94 to D2Mit304, three separate QTLs were detected in the
      HS animals. The data obtained confirm the usefulness of HS mice for the fine
      mapping of QTLs to a resolution of 2 cM or less.

PMID- 11529278
TI  - Genomewide search for epistasis in a complex trait: pentobarbital withdrawal
      convulsions in mice.
AB  - The well-documented difference in pentobarbital withdrawal severity between
      DBA/2J and C57BL/6J mice offers the opportunity to study how differences between
      allelic variants influence pentobarbital withdrawal via their additive and/or
      dominance effects and to identify modifier loci that also influence the trait via
      gene-gene interactions (a form of epistasis). Previous work in our laboratory
      identified seven provisional quantitative trait loci (QTLs) for pentobarbital
      withdrawal using BXD recombinant inbred strains. To date, only one of these QTLs
      has been confirmed, Pbw1. We hypothesized that other loci that act epistatically
      may also influence genetic variance in pentobarbital withdrawal severity. Using
      Epistat, a program developed to carry out full-genome searches for epistasis, we
      identified six provisional epistatic interactions (p < .002) between the
      provisional QTLs and modifier loci elsewhere in the genome. Verification testing
      of these interactions using 404 B6D2F2 mice provided supporting evidence that a
      QTL on chromosome 11 contributes to genetic variance in pentobarbital withdrawal,
      but only in the presence of a modifier allele on distal chromosome 1 (p = .0004).
      This modifier is in the same genomic vicinity as loci detected for a variety of
      withdrawal and seizure phenotypes.

PMID- 11529279
TI  - Immunological intervention with anti-immunoglobulin-E antibody to prevent asthma
      exacerbations.

PMID- 11529280
TI  - Hypoxic pulmonary hypertension in man: what minimum daily duration of hypoxaemia
      is required?

PMID- 11529281
TI  - The anti-IgE antibody omalizumab reduces exacerbations and steroid requirement in
      allergic asthmatics.
AB  - The clinical benefit and steroid-sparing effect of treatment with the anti
      immunoglobulin-E (IgE) antibody, omalizumab, was assessed in patients with
      moderate-to-severe allergic asthma. After a run-in period, 546 allergic
      asthmatics (aged 12-76 yrs), symptomatic despite inhaled corticosteroids (500
      1,200 microg daily of beclomethasone dipropionate), were randomized to receive
      double-blind either placebo or omalizumab every 2 or 4 weeks (depending on body
      weight and serum total IgE) subcutaneously for 7 months. A constant
      beclomethasone dose was maintained during a 16-week stable-steroid phase and
      progressively reduced to the lowest dose required for asthma control over the
      following 8 weeks. The latter dose was maintained for the next 4 weeks. Asthma
      exacerbations represented the primary variable. Compared to the placebo group,
      the omalizumab group showed 58% fewer exacerbations per patient during the stable
      steroid phase (p<0.001). During the steroid-reduction phase, there were 52% fewer
      exacerbations in the omalizumab group versus the placebo group (p<0.001) despite
      the greater reduction of the beclomethasone dosage on omalizumab (p<0.001).
      Treatment with omalizumab was well tolerated. The incidence of adverse events was
      similar in both groups. These results indicate that omalizumab therapy safely
      improves asthma control in allergic asthmatics who remain symptomatic despite
      regular use of inhaled corticosteroids and simultaneous reduction in
      corticosteroid requirement.

PMID- 11529282
TI  - Improved asthma control with budesonide/formoterol in a single inhaler, compared
      with budesonide alone.
AB  - Budesonide/formoterol in a single inhaler was compared with budesonide alone, and
      with concurrent administration of budesonide and formoterol from separate
      inhalers, in patients with asthma, not controlled with inhaled
      glucocorticosteroids alone. In this 12-week, double-blind, randomized, double
      dummy study, 362 adult asthmatics (forced expiratory volume in one second 73.8%
      of predicted, inhaled glucocorticosteroid dose 960 microg x day(-1)) received
      single inhaler budesonide/formoterol (Symbicort Turbuhaler) 160/4.5 microg, two
      inhalations b.i.d., or corresponding treatment with budesonide, or budesonide
      plus formoterol via separate inhalers. There was a greater increase in morning
      peak expiratory flow (PEF) with single-inhaler (35.7 L x min(-1)) and separate
      inhaler (32.0 L x min(-1)) budesonide and formoterol, compared with budesonide
      alone (0.2 L x min(-1); p<0.001, both comparisons); the effect was apparent after
      1 day (p<0.001 versus budesonide, both comparisons). Similarly, evening PEF, use
      of rescue medication, total asthma symptom scores and percentage of symptom-free
      days improved more with both single inhaler and separate inhaler therapy than
      with budesonide alone, as did asthma control days (approximately 15% more,
      p<0.001 versus budesonide, both comparisons, with a marked increase in the first
      week). All treatments were well tolerated and the adverse event profile was
      similar in all three treatment groups. It is concluded that single inhaler
      therapy with budesonide and formoterol is a clinically effective and well
      tolerated treatment for patients with asthma that is not fully controlled by
      inhaled glucocorticosteroids alone.

PMID- 11529283
TI  - Unaltered perception of dyspnoea during treatment with long-acting beta2
      agonists.
AB  - There is the possibility that during treatment with inhaled long-acting beta2
      agonists that a loss of perception of dyspnoea might occur and that the forced
      expiratory volume in one second (FEV1) might fall precipitously during bronchial
      provocation. This study investigated these possibilities during methacholine
      provocation, continued until there was > or =30% fall in FEV1, mimicking a
      moderate asthma attack. Nineteen asthmatic patients were asked to score their
      dyspnoea as a Borg score during provocation with methacholine. One hour prior to
      this provocation, the patients used the last morning dose of 14 days treatment
      with either formoterol (twice daily 24 microg by Turbuhaler), salmeterol (twice
      daily 100 microg by Diskhaler) and placebo in a double-blind, randomized, double
      dummy, cross-over design. The perception of dyspnoea, expressed as the Borg score
      divided by the change in FEV1 at > or =30% fall in FEV1, was similar on the three
      test days at 0.067, 0.076 and 0.074%(-1) after formoterol, salmeterol and placebo
      treatment, respectively (p=0.16). The slope of the methacholine dose response
      curve did not differ (p=0.52). In conclusion, no suggestion was found for an
      abnormal perception of dyspnoea or an exaggerated fall in forced expiratory
      volume in one second during provocation with methacholine under long-acting beta2
      agonist treatment.

PMID- 11529284
TI  - A new asthma severity index: a predictor of near-fatal asthma?
AB  - Bronchial hyperresponsiveness (BHR), measured as the provocative dose of inhaled
      histamine or methacholine required to produce a 20% fall in forced expiratory
      volume in one second (FEV1) (PD20), is widely used as one of the indices of
      asthma severity. Excessive bronchoconstriction, reflected by the maximal
      percentage fall in forced vital capacity (FVC) at PD20 (deltaFVC %) during BHR
      testing, is considered to be the most important pathophysiological determinant in
      fatal asthma. The present study hypothesized that an index which combines both
      the ease of airway narrowing and excessive bronchoconstriction, deltaFVC
      %/log(PD20), may be better in assessing asthma severity, especially in those at
      risk of near-fatal attacks. The dose-response curves of 46 asthmatics who
      underwent methacholine challenge testing were studied. Group 1 (n=14) patients
      had mild disease, Group 2 (n=21) had moderate disease and Group 3 (n=11) had
      severe disease, as classified according to the Global Initiative for Asthma. Nine
      patients had prior intubation for near-fatal asthma. deltaFVC %/log (PD20) was
      better than deltaFVC % and PD20 in categorizing patients into the three severity
      groups (p<0.0001), but more importantly, it was able to discriminate patients
      with previous intubation from those without (p=0.04). It also correlated better
      with FEV1 (% predicted), frequency of symptoms and inhaled steroid requirement
      than either index alone. It is concluded that the percentage fall in forced vital
      capacity/log of the provocative dose causing a 20% fall in forced expiratory
      volume in one second combines information on the ease and excessive degrees of
      airway narrowing in asthma. This new index may be better at assessing asthma
      severity and in discriminating those at risk of near-fatal attacks.

PMID- 11529285
TI  - Chronic intermittent hypercapnic hypoxia increases pulmonary arterial pressure
      and haematocrit in rats.
AB  - Sleep-disordered breathing is associated with pulmonary hypertension and raised
      haematocrit. The multiple episodes of apnoea in this condition cause chronic
      intermittent hypoxia and hypercapnia but the effects of such blood gas changes on
      pulmonary pressure or haematocrit are unknown. The present investigation tests
      the hypothesis that chronic intermittent hypercapnic hypoxia causes increased
      pulmonary arterial pressure and erythropoiesis. Rats were treated with
      alternating periods of normoxia and hypercapnic hypoxia every 30 s for 8 h per
      day for 5 days per week for 5 weeks, as a model of the intermittent blood gas
      changes which occur in sleep-disordered breathing in humans. Haematocrit, red
      blood cell count and haemoglobin concentration were measured each week and
      systemic and pulmonary arterial blood pressure and heart weight were measured
      after 5 weeks. In relation to control, chronic intermittent hypercapnic hypoxia
      caused a significant increase in systemic (104.3+/-4.7 mmHg versus 121.0+/-10.4
      mmHg) and pulmonary arterial pressure (20.7+/-6.8 mmHg versus 31.3+/-7.2 mmHg),
      right ventricular weight (expressed as ratios) and haematocrit (45.2+/-1.0%
      versus 51.5+/-1.5%). It is concluded that the pulmonary hypertension and elevated
      haematocrit associated with sleep-disordered breathing is caused by chronic
      intermittent hypercapnic hypoxia.

PMID- 11529287
TI  - Exercise tolerance in children with cystic fibrosis undergoing lung
      transplantation assessment.
AB  - The aim of this study was to compare the 6-min walk test against the recently
      developed 3-min step test, as measures of exercise tolerance in children with
      moderate to severe cystic fibrosis (CF) lung disease referred for lung
      transplantation assessment. Twenty-eight children with CF (16 girls, 12 boys),
      with a mean age of 13.7 yrs (range 7.2-17.8 yrs) and mean forced expiratory
      volume in one second of 34% predicted (range 17%-67%) were recruited. All
      subjects performed both the 6-min walk and 3-min step-tests. Outcome measures
      were maximum rise in heart rate (HR), and maximum fall in arterial oxygen
      saturation (Sa,O2). There was no significant difference in resting HR or Sa,O2
      prior to starting the two tests. Both step and walk tests produced significant
      rises in median HR (from 114-149 min(-1), p<0.0005, and 119-138 min(-1),
      p<0.0005, respectively) and significant falls in Sa,O2 (both from 94-92%,
      p<0.0005). The step test produced a significantly greater percentage rise in HR
      (30% versus 18%, p<0.0005) and a significantly greater percentage fall in Sa,O2
      (4% versus 2%, p=0.002). Bland-Altman analysis gave wide 95% limits of agreement
      (10.7-29.3% for rise in HR, -2.14.6% for fall in Sa,O2). The step test was well
      tolerated. The 3-min step test produced a greater fall in Sa,O2 and a greater
      rise in HR than the 6-min walk test in children with moderate to severe CF lung
      disease. It may be of value when assessing a child's suitability for lung
      transplantation.

PMID- 11529286
TI  - Response of nitric oxide pathway to L-arginine infusion at the altitude of 4,350
      m.
AB  - It was hypothesized that hypoxia may inhibit nitric oxide (NO) production by
      reducing the availability of endothelial NO synthase (NOS III) substrate. To
      evaluate the effect of L-arginine on the NO release in high altitude, 11 subjects
      were infused with L-arginine (0.5 g x kg(-1)) during 30 min in normoxia and after
      36 h at 4,350 m (hypoxia). The L-citrulline and cyclic guanosine monophosphate
      (cGMP) concentrations were measured to investigate NO synthesis and guanylyl
      cyclase activity respectively. L-citrulline concentration, arterial oxygen
      saturation (Sa,O2), systemic blood pressure, heart rate and acute mountain
      sickness (AMS) score were measured at rest and 15, 30 and 45 min after starting
      infusion. The results showed that baseline L-citrulline was lower in hypoxia
      (p<0.05). L-arginine infusion increased L-citrulline concentration in both
      conditions. However, in hypoxia L-citrulline concentration remained lower than in
      normoxia (p<0.05). The concentration of cGMP was lower in hypoxia (p<0.05). In
      hypoxia, Sa,O2 increased from 15 min after the start of the infusion to 45 min
      (p<0.05). Blood pressure and heart rate were not affected by L-arginine infusion.
      Subjects who experienced symptoms of AMS showed a slight decrease in AMS score
      with L-arginine. The decreased L-citrulline suggests a hypoxia-induced impairment
      of nitric oxide synthase III or a decrease in L-arginine availability. The
      improvement of arterial oxygen saturation by pretreatment with L-arginine could
      be ascribed to an enhancement of the ventilation/perfusion ratio. Collectively,
      these results are consistent with a decrease in nitric oxide production in
      hypoxia that could be antagonized by supplying nitric oxide synthase cosubstrate.

PMID- 11529288
TI  - Factors associated with poor pulmonary function: cross-sectional analysis of data
      from the ERCF. European Epidemiologic Registry of Cystic Fibrosis.
AB  - The European Epidemiologic Registry of Cystic Fibrosis began collecting
      longitudinal data on European cystic fibrosis patients in 1994. A cross-sectional
      analysis was performed to identify the factors associated with low values of %
      predicted forced expiratory volume in one second (FEV1) upon patient enrollment.
      Data from 7,010 patients aged > or =6 yrs were included. Clinical conditions,
      microbiological isolates and medications reported at enrollment or within the
      following 180 days were analysed for age-specific associations. Factors
      associated with FEV1 that were lower by >10% of pred values were: lower weight
      for age percentiles, haemoptysis, pneumothorax, pulmonary symptoms at
      presentation, Pseudomonas aeruginosa, Burkholderia cepacia, oral corticosteroids,
      nonsteroid anti-inflammatory drugs, dornase alfa, oxygen and assisted ventilation
      and, in patients >12 yrs old only, use of airway clearance techniques, inhaled
      bronchodilators, oral nutritional supplements, pancreatic enzymes and insulin or
      oral hypoglycaemics. Slightly impaired lung function (5-10%) was associated with:
      diabetes (> or = 18-yrs-old), gastro-oesophageal reflux, allergic
      bronchopulmonary aspergillosis, asthma-like symptoms, portal hypertension,
      Aspergillus spp. and Candida spp. Sex, Haemophilus influenzae and Staphylococcus
      aureus were not associated with impaired pulmonary status. Regular exercise
      (especially in older patients) and nasal polyposis were associated with slightly
      better FEV1. The results confirm those of previous studies and suggest selective
      prescribing in sicker patients.

PMID- 11529289
TI  - Influence of neonatal screening and centralized treatment on long-term clinical
      outcome and survival of CF patients.
AB  - After an experimental neonatal screening program for cystic fibrosis (CF) from
      1973-1979, a follow-up study took place from 1980-1997. Patients were treated at
      specialized centres (C) or at local hospitals (non-C). Aims of the study were: 1)
      to determine whether the previously reported benefits from screening persisted
      with time and after adjustment for confounding variables; and 2) to investigate
      whether centre treatment was associated with improved prognosis of CF patients.
      Prognosis of patients detected by screening (S; n=24) was compared with patients
      detected clinically, born during (non-S; n=29) and after the screening programme
      (post-S; n=39). In addition, prognosis was compared between 45 C and 47 non-C
      patients. Multivariable regression analysis was used to compare survival and
      mixed-effects model regression analysis was used to compare clinical outcome
      between patients. The analyses included the variables screening, centre
      treatment, sex, meconium ileus and genotype. S patients had a significantly
      smaller decline in forced expiratory volume in one second (FEVI) (difference
      +2.74% predicted) and significantly lower immunoglobulin-G (IgG) levels
      (difference -473.69 mg x dL(-1)) than non-S patients until 12 yrs of age. At 12
      yrs of age, vital capacity was significantly higher in S patients than in non-S
      patients (difference +362.79 mL). Survival seemed to be best for S patients
      compared to both non-S and post-S patients. Post-S patients were significantly
      heavier (difference in SD weight +0.77), had a significantly smaller decline in
      FEV1 (difference +2.80% pred) and lower IgG levels (difference -453.04 mg x dL(
      1)) than non-S patients until 12 yrs of age. C patients had a significantly
      improved survival (relative risk (RR) 0.18, 95% confidence interval 0.05-0.57)
      than non-C patients. Early diagnosis through neonatal screening leads to better
      preservation of lung function in the long term in cystic fibrosis patients.
      Management of cystic fibrosis patients in specialized centres improves survival.

PMID- 11529290
TI  - Urinary excretion reflects lung deposition of aminoglycoside aerosols in cystic
      fibrosis.
AB  - Using nebulization to deliver aminoglycosides may be of benefit in cystic
      fibrosis (CF) patients colonized by Pseudomonas aeruginosa. However, one problem
      with this route is the absence of clinical parameters allowing estimation of the
      mass of drug deposited in the lungs (MDL). The aim of this study was to assess
      whether aminoglycoside excretion in the urine reflects the MDL. Fourteen studies
      were performed in seven CF patients. Amikacin was mixed with albumin labelled
      with 99mTc and nebulized with an ultrasonic nebulizer. The MDL was determined by
      the mass-balance technique. Urine was collected during the 24 h following
      inhalation and was assayed for amikacin by fluorescence polarization immunoassay
      (FPIA). The mean+/-SEM MDL was 14.0+/-2.2% of the nebulizer charge. The mean+/
      SEM amount of amikacin excreted in the urine was 20.9+/-4.5 mg and correlated
      with the MDL (r=0.93; p=0.0001). There was, however, wide intersubject
      variability in both deposition and excretion in the urine. Monitoring excretion
      of aminoglycosides in the urine allows noninvasive estimation of the mass of drug
      deposited in the lung in cystic fibrosis patients, which might be useful to
      assess the dose-response relationship in groups of patients, but intersubject
      variability prevents its use for individual follow-up.

PMID- 11529292
TI  - Comparison of resistance measured by the interrupter technique and by passive
      mechanics in sedated infants.
AB  - Airways resistance measured by the interrupter technique (Rint) requires little
      patient cooperation and has been successfully used in young children, but little
      studied in infants. The authors aimed to evaluate the measurement of Rint in
      infants, using a commercially available device (the MicroRint), by comparing it
      with an established technique to measure respiratory resistance: the single
      breath occlusion technique (SBT); and a measure of airflow obstruction during
      forced expiration. Infants <18 months old with a history of wheeze, sedated with
      triclofos for pulmonary function testing, had measurements taken and compared to
      Rint (using the MicroRint), respiratory system resistance (Rrs) by SBT, and to
      maximal flow at functional residual capacity (V'maxFRC). Paired data from 25 of
      37 infants studied was obtained. There was a significant difference between Rint
      (mean 2.94+/-0.68) and Rrs (4.02+/-0.87), but the two measures were strongly
      correlated (r=0.7). Rint was negatively correlated with V'maxFRC (r=-0.63).
      Smaller infants failed to trigger the MicroRint. Interrupter resistance values in
      infants are significantly lower than values of respiratory system resistance
      obtained by passive mechanics. However, there is a strong correlation between the
      two measurements, as well as between resistance measured using the interrupter
      technique and maximal flow at functional residual capacity, which indicates that
      resistance measured using the interrupter technique may be a useful marker of
      airway obstruction in infants. There remain a number of theoretical and technical
      problems which require further exploration.

PMID- 11529291
TI  - Pre- and postnatal parental smoking and wheeze in infancy: cross cultural
      differences. Avon Study of Parents and Children (ALSPAC) Study Team, European
      Longitudinal Study of Pregnancy and Childhood (ELSPAC) Co-ordinating Centre.
AB  - In longitudinal cohort studies, the relationships between prenatal and postnatal
      tobacco smoke exposure and infant wheezing illnesses were compared in two
      geographically defined populations in Avon, UK and Brno and Znojmo in the South
      Moravian Region of the Czech Republic. Pregnant females living in defined regions
      and with expected dates of delivery between defined dates were recruited. Females
      completed self-report questionnaires during pregnancy and when their infant was 6
      months old. For this analysis, responses to questions about smoking during
      pregnancy, environmental tobacco smoke (ETS) exposure and reported wheezing
      illnesses of infants at 6 months after birth were used. Odds ratios for wheeze in
      relation to the smoking variables were calculated with adjustment for potential
      confounding effects. The prevalence of smoking during pregnancy was higher in
      Avon (17.5%) than the Czech Republic (7.1%). Exposure of infants to ETS during
      the first 6 months after birth was also reported to be higher in Avon (35.5%)
      than the Czech Republic (9.7%). The prevalence of reported wheezing by 6 months
      of age was 21.4% in Avon and 10.3% in Brno and Znojmo. In Avon, there was a
      significant relationship between infant wheeze and maternal smoking during
      pregnancy (odds ratio (95% confidence interval) 1.30 (1.09-1.56), p=0.004) but
      not with environmental exposure after birth (1.11 (0.98-1.25)). In contrast, in
      Brno and Znojmo in the Czech Republic, there was a significant relationship
      between infant wheeze and ETS exposure (1.66 (1.17-2.36), p=0.04) but not with
      maternal smoking during pregnancy (0.99 (0.64-1.55)). This study demonstrated an
      apparent difference in the associations between prenatal and postnatal tobacco
      smoke exposure and infant wheezing illnesses in two populations with different
      smoking prevalence. The relationships were independent of a number of potential
      confounding variables that have been associated with infant wheezing. Possible
      explanations of these observations include dose-related effects of prenatal and
      postnatal tobacco smoke exposure of infants.

PMID- 11529293
TI  - Forced oscillation measurements do not affect upper airway muscle tone or sleep
      in clinical studies.
AB  - Upper airway obstruction in the sleep apnoea/hypopnoea syndrome (SAHS) can be
      easily assessed by measuring respiratory impedance with the forced oscillation
      technique (FOT). This methodology has been proposed as a useful clinical tool
      both for the diagnosis of sleep breathing disorders and for continuous positive
      airway pressure (CPAP) titration. However, previous studies suggest that the
      application of high-frequency pressure oscillation to the upper airway may induce
      changes in the electroencephalogram (EEG) or upper airway muscle function. The
      effect of FOT measurements on upper airway muscle tone and EEG in clinical sleep
      studies was examined. Seven patients with moderate SAHS were included (age: 54+/
      11 yrs; apnoea/hypopnoea index: 43+/-21 events x h(-1); body mass index: 30+/-2
      kg x m(-2)). Genioglossus surface electromyogram activity (EMGgg) and EEG signal
      were analysed with and without FOT application (frequency: 5 Hz and 30 Hz; peak
      to-peak pressure oscillation: 1 cmH2O) during stable sleep. Measurements were
      carried out in two different situations. Step 1: applying FOT during episodes of
      obstructive events or flow limitation; and step 2: during prolonged periods of
      normal breathing at optimal CPAP. The root mean square of EMGgg activity and fast
      Fourier analysis (alpha and delta bands) of the EEG signal were performed. The
      application of FOT did not increase EMGgg activity in any of the situations
      studied. In addition, no evidence of the effects on EEG was found: alpha/delta
      relationship: awake:0.70, baseline sleep:0.13, FOT(5 Hz):0.18, FOT(30 Hz):0.11.
      The presented results suggest that the use of forced oscillation technique over
      the ranges of frequency and amplitude proposed for clinical sleep studies does
      not induce changes in upper airway muscle activity and neurological variables in
      patients with sleep apnoea/hypopnoea syndrome.

PMID- 11529294
TI  - Apnoea characteristics across the night in severe obstructive sleep apnoea:
      influence of body posture.
AB  - Several studies have reported changes in apnoea characteristics across the night
      in patients with obstructive sleep apnoea (OSA). However, the effect of body
      posture on these changes has not been evaluated. The purpose of this study was to
      assess how body posture influences sleep apnoea characteristics across the night
      in severe OSA. Polysomnograms of 30 patients with severe OSA who had > or = 30
      apnoeic episodes in the lateral position and 30 in the supine position during
      Stage 2 sleep, in the early, middle and late sleep periods were analysed. For
      each of the 30 events in each body position, the following variables were
      evaluated: apnoea duration; minimum saturation; change in saturation; duration of
      arousal; maximum snoring loudness and change in cardiac frequency. Although at
      any time during the night, apnoeas in the supine posture were more severe than
      those in the lateral position, a time effect across the night was found only for
      apnoea duration, change in cardiac frequency and duration of arousal. Body
      position did not affect the time trend for these variables across the night. The
      best fit for the changes of these three variables across the night was a
      quadratic time trend. It was concluded that in severe obstructive sleep apnoea
      during Stage 2 sleep, body position does not significantly affect the time trends
      of apnoea characteristics across the night. These data provide support for the
      participation of sleep-dependent mechanisms (homeostatic and circadian) in the
      determination of apnoea characteristics across the night.

PMID- 11529295
TI  - Changes in xylosyltransferase activity and in proteoglycan deposition in
      bleomycin-induced lung injury in rat.
AB  - Several lines of evidence support the hypothesis of the involvement of altered
      proteoglycan deposition in the development of lung diseases. UDP-D-xylose: core
      protein beta-D-xylosyltransferase (UDP-xylosyltransferase; EC 2.4.2.26) is a key
      enzyme for the glycosylation of proteoglycan core proteins. This study examined
      the catalytic activity of UDP-xylosyltransferase in lung tissue and in isolated
      fibroblasts, as well as the deposition of the proteoglycans versican, biglycan
      and decorin in rat lung tissue during bleomycin-induced lung injury. Rats were
      given, endotracheally, a single dose of bleomycin. Deposition of proteoglycans in
      lung tissue was assessed by immunohistochemistry and the catalytic activity of
      xylosyltransferase was determined with an acceptor peptide of the sequence Q-E-E
      E-G-S-G-G-G-Q-G-G as a substrate. The results show coincidence of increasing
      xylosyltransferase activities in lung tissue with accumulation of versican at
      alveolar entrance rings and in fibrotic regions in close proximity to alpha
      smooth muscle actin-positive cells. In contrast, no changes in biglycan and
      decorin deposition in fibrotic lungs were observed, except for decorin in
      alveolar type II pneumocytes and alveolar macrophages. Bleomycin treatment of
      isolated rat lung fibroblasts resulted in a concentration-dependent increase of
      xylosyltransferase activity up to 2 mU bleomycin x mL(-1). The data suggest a
      participation of myofibroblasts with increased xylosyltransferase activities in
      accumulation of versican in fibrotic foci of injured lung tissue at the early
      stages of development of lung fibrosis.

PMID- 11529296
TI  - Computed tomography of pulmonary sarcoid-like granulomas induced by complete
      Freund's adjuvant in rats.
AB  - Intravenous injection of complete Freund's adjuvant (CFA) in rats has been
      proposed as an experimental model for pulmonary sarcoidosis, but only some
      animals develop granulomas. Because the detection of the presence of granulomas
      and evaluation of the extent of the reaction has required histological
      evaluation, this model has been of limited use in following the evolution of the
      granulomatous process. The present study evaluated the ability of lung computed
      tomography (CT) scanning to identify in vivo pulmonary granulomas induced by CFA
      in rats. Wistar rats were injected with CFA to induce pulmonary sarcoid-like
      granulomas, and the presence and extent of pulmonary abnormalities, as detected
      by spiral CT and histopathological analysis, were compared. Spiral CT had a high
      sensitivity and specificity for the detection of sarcoid-like granulomas in rats
      injected with CFA. The extent of the pulmonary granulomatous reaction as assessed
      by the two techniques strongly correlated (r=0.93, p<0.01). In contrast, the mean
      density of lungs containing granulomas was not significantly different from that
      of lungs with no granulomatous reaction. Thus, lung computed tomography appears
      to be a valuable tool for the in vivo evaluation of the pulmonary granulomatous
      reaction induced by complete Freund's adjuvant in rats. With the help of computed
      tomography, this experimental model should be suitable for the sequential study
      of pulmonary sarcoid-like granulomas, particularly in response to various
      therapeutic strategies.

PMID- 11529297
TI  - A prospective comparison of nursing home acquired pneumonia with community
      acquired pneumonia.
AB  - Nursing home acquired pneumonia (NHAP) is thought to be clinically distinct from
      community acquired pneumonia (CAP). This observation, based on studies conducted
      mainly in North America, may not be relevant in countries with a different
      healthcare system. The authors describe an 18-month prospective cohort study of
      437 patients admitted to hospital with CAP, 40 (9%) of whom came from nursing
      homes. Detailed microbiological tests were performed in a subset of patients over
      12 months. Patients with NHAP were less likely to have a productive cough (odds
      ratio (OR) 0.4, p=0.02) or pleuritic pain (OR 0.1, p=0.03), but they were more
      likely to be confused (OR 2.6, p<0.001). They had poorer functional status
      (p<0.001) and more severe disease (p=0.03). Mortality was higher compared to CAP
      (53% versus 13%), but this was mainly explained by prior functional status (OR
      0.5, after adjustment for functional status). Pathogens were identified in 68% of
      22 NHAP and 80% of 44 matched CAP patients. Streptococcus pneumoniae was the most
      common (55% NHAP, 43% CAP). Atypical pathogens, enteric Gram negative bacilli and
      Staphylococcus aureus were uncommon. In conclusion, differences in functional
      status accounted for the increased mortality in nursing home acquired pneumonia
      compared to community acquired pneumonia. The pathogens implicated were similar.
      No grounds for a difference in choice of empirical antibiotics were apparent.

PMID- 11529298
TI  - Guidelines of tuberculosis preventive therapy for HIV-infected persons: a
      prospective, multicentre study. GISTA (Gruppo Italiano di Studio Tubercolosi e
      AIDS).
AB  - The aim of this study was to assess the degree of implementation of national
      guidelines for isoniazid preventive therapy (IPT) among human immunodeficiency
      virus (HIV)-infected individuals and factors affecting the impact of the
      programme. Twenty-eight infectious disease hospital units in Italy participated
      in this observational, multicentre, prospective cohort study. A number of HIV
      infected subjects, (n=1,705) seen for the first time as outpatients, were
      included in this analysis. Of the subjects considered, 1,215 out of the 1,705
      completed purified protein derivative (PPD) screening. Variables independently
      associated with offering and completion of PPD screening included having acquired
      immune deficiency syndrome (AIDS), higher educational levels and currently
      receiving therapy. Overall, 103 subjects were identified as candidates for IPT.
      Of these subjects, five had tuberculosis and 15 had contraindications to IPT.
      Forty subjects agreed to start IPT, and 29 completed a full-course regimen. The
      incidence of tuberculosis among IPT candidates who either did not begin or
      discontinued IPT was 6.1 per 100 person-yrs, while no cases of tuberculosis were
      observed in subjects completing IPT. Several factors may limit the implementation
      of an isoniazid preventive therapy programme for human immunodeficiency virus
      infected persons. Physicians fail to offer purified protein derivative screening
      to patients with high degrees of immunodeficiency, and those with a more intense
      workload seem to pay less attention to this test. The high number of
      contraindications among patients and their low level of acceptance further
      affects the impact of isoniazid preventive therapy.

PMID- 11529299
TI  - The tuberculin skin test in relation to immunological in vitro reactions in BCG
      vaccinated healthcare workers.
AB  - The aim was to study the tuberculin skin test in relation to immunological in
      vitro reactions in bacille Calmette-Guerin (BCG)-vaccinated healthcare workers.
      The present study was performed in Sweden, a country with a low incidence of
      tuberculosis, a high BCG vaccination efficacy and high tuberculin conversion
      rates. BCG-vaccinated healthcare workers (n=381) were tuberculin skin tested.
      From these, 11 subjects with negative tuberculin reactions (<6 mm) were matched
      for age and sex with 11 subjects with large positive reactions (> or = 15 mm).
      Lymphocyte transformation and the production of interferon-gamma (IFN-gamma) were
      analysed after stimulation in vitro of peripheral blood mononuclear cells with
      tuberculin purified protein derivative, heat-killed tubercle bacilli and a
      culture filtrate from tubercle bacilli. In the tuberculin-positive group the
      lymphocyte transformation response was 2-3 times larger, and IFN-gamma production
      was 7-10 times larger, than in the tuberculin-negative group (p<0.001). The
      present results suggest that a positive tuberculin skin test in bacille Calmette
      Guerin-vaccinated subjects indicates a stronger immune response of the protective
      T-helper 1-type than does a negative test. In similar settings, the study
      supports the traditional practice of regarding the tuberculin skin test in
      bacille Calmette-Guerin-vaccinated subjects as an indicator of a protective
      immune response against tuberculosis.

PMID- 11529300
TI  - Virtual tools for imaging of the thorax.
AB  - Helical computed tomography (HCT) allows for volume acquisition of the entire
      thorax during a single apnoea. Combination of HCT acquisition with synchronous
      vascular enhancement gives rise to HCT angiography (HCTA). In the last decade,
      HCT and HCTA have revolutionized the diagnosis of thoracic diseases, modifying
      many diagnostic algorithms. Because HCT provides for a true volume acquisition
      free of respiratory misregistration, three-dimensional (3D) rendering techniques
      can be applied to HCT acquisitions. As these 3D rendering techniques present the
      HCT information in a different format to the conventional transaxial CT slices,
      they can be summarized as virtual tools. The purpose of this review is to give
      the readers the most important technical aspects of virtual tools, to report
      their application to the thorax, to answer clinical and scientific questions, and
      to stress their importance for patient management, clinical decision making, and
      research.

PMID- 11529301
TI  - Statistics for the European Respiratory Journal.
AB  - This review summarizes statistical methods likely to be needed by researchers. It
      is not a replacement for a statistics book, and almost no symbols or mathematics
      are used. It seeks to guide researchers to the appropriate methods and to make
      them aware of some common pitfalls. Sections deal with methods for quantitative
      outcomes, both basic and more advanced, and parallel methods for qualitative or
      categorical outcomes. Reference is made to papers using the more advanced methods
      in the European Respiratory Journal in order that their relevance may be
      appreciated. The paper seeks to improve the quality of papers submitted to the
      European Respiratory Journal, to reduce the revisions to papers required of
      authors, and to enable readers of the journal to gain more insight into the
      interpretation of results.

PMID- 11529302
TI  - Management of malignant pleural effusions.

PMID- 11529303
TI  - "Haemoxygenase-1 induction and exhaled markers of oxidative stress in lung
      diseases", summary of the ERS Research Seminar in Budapest, Hungary, September,
      1999.
AB  - In recent years, there has been increasing interest in noninvasive monitoring of
      airway inflammation and oxidative stress. Several volatile and nonvolatile
      substances can be measured in exhaled breath and have been suggested as potential
      biomarkers of these events. Exhaled gases, including carbon monoxide (CO),
      alkanes (ethane, pentane), and substances measured in breath condensate, such as
      hydrogen peroxide (H2O2) and isoprostanes were all suggested as potential markers
      of oxidative stress in the lung. A European Respiratory Society (ERS)
      International Research Seminar entitled "Haemoxygenase-1 induction and exhaled
      markers of oxidative stress in lung diseases" was organized by the Airway
      Regulation and Provocation Group of the Clinical Allergy and Immunology Assembly
      in Budapest, Hungary in September, 1999 to integrate the latest knowledge on
      these issues and accelerate further improvement in this area. During this 2-day
      event several issues were raised about: the use and standardization of
      measurements in exhaled breath; problems of measuring expired H2O2 and other
      mediators in breath condensate; role and regulation of haemoxygenase (HO)-1 in
      the lung; and conditions and factors influencing exhaled CO. This report is a
      summary of the main presentations at the seminar, together with the current areas
      of research in this rapidly expanding field.

PMID- 11529304
TI  - A 40-yr-old male with cough, haemoptysis and increasing dyspnoea.

PMID- 11529306
TI  - Complexity in biological information processing. Proceedings of a symposium.
      Berlin, Germany, 4-6 July 2000.

PMID- 11529305
TI  - Resistance to penicillin among the Streptococcus pneumoniae in Turkey.

PMID- 11529307
TI  - From genes to whole organs: connecting biochemistry to physiology.
AB  - The successful analysis of physiological processes requires quantitative
      understanding of the functional interactions between the key components of cells,
      organs and systems, and how these interactions change in disease states. This
      information does not reside in the genome, or even in the individual proteins
      that genes code for. There is therefore no alternative to copying nature and
      computing these interactions to determine the logic of healthy and diseased
      states. The rapid growth in biological databases, models of cells, tissues and
      organs, and in computing power has made it possible to explore functionality all
      the way from the level of genes to whole organs and systems. Examples are given
      of genetic modifications of the Na+ channel protein in the heart that predispose
      people to ventricular fibrillation, and of multiple target therapy in drug
      development. Complexity in biological systems also arises from tissue and organ
      geometry. This is illustrated using modelling of the whole heart.

PMID- 11529308
TI  - Development of high-throughput tools to unravel the complexity of gene expression
      patterns in the mammalian brain.
AB  - Genomes of animals contain between 15000 (e.g. Drosophila) and 50000 (human,
      mouse) genes, many of which encode proteins involved in regulatory processes. The
      availability of sequence data for many of these genes opens up opportunities to
      study complex genetic and protein interactions that underlie biological
      regulation. Many examples demonstrate that an understanding of regulatory
      networks consisting of multiple components is significantly advanced by a
      detailed knowledge of the spatiotemporal expression pattern of each of the
      components. Gene expression patterns can readily be determined by RNA in situ
      hybridization. The unique challenge emerging from the knowledge of the sequence
      of entire genomes is that assignment of biological functions to genes needs to be
      carried out on an appropriately large scale. In terms of gene expression analysis
      by RNA in situ hybridization, efficient technologies need to be developed that
      permit determination and representation of expression patterns of thousands of
      genes within an acceptable time-scale. We set out to determine the spatial
      expression pattern of several thousand genes encoding putative regulatory
      proteins. To achieve this goal we have developed high-throughput technologies
      that allow the determination and visualization of gene expression patterns by RNA
      in situ hybridization on tissue sections at cellular resolution. In particular,
      we have invented instrumentation for robotic in situ hybridization capable of
      carrying out in a fully automated fashion, all steps required for detecting sites
      of gene expression in tissue sections. In addition, we have put together hardware
      and software for automated microscopic scanning of gene expression data that are
      produced by RNA in situ hybridization. The potential and limitations of these
      techniques and our efforts to build a Web-based database of gene expression
      patterns are discussed.

PMID- 11529309
TI  - Design of immune-based interventions in autoimmunity and viral infections--the
      need for predictive models that integrate time, dose and classes of immune
      responses.
AB  - The outcome of both autoimmune reactions and antiviral responses depends on a
      complex network of multiple components of the immune system. For example, most
      immune reactions can be viewed as a balance of aggressive and regulatory
      processes. Thus, a component of the immune system that has beneficial effects in
      one situation might have detrimental effects elsewhere: organ-specific immunity
      and autoimmunity are both governed by this paradigm. Additionally, the precise
      timing and magnitude of an immune response can frequently be more critical than
      its composition for determining efficacy as well as damage. These issues make the
      design of immune-based interventions very difficult, because it is frequently
      impossible to predict the outcome. For example, certain cytokines can either cure
      or worsen autoimmune processes depending on their dose and timing in relation to
      the ongoing disease process. Consequently, there is a strong need for models that
      can predict the outcome of immune-based interventions taking these considerations
      into account.

PMID- 11529310
TI  - Regulation of gene expression by action potentials: dependence on complexity in
      cellular information processing.
AB  - Nervous system development and plasticity are regulated by neural impulse
      activity, but it is not well understood how the pattern of action potential
      firing could regulate the expression of genes responsible for long-term adaptive
      responses in the nervous system. Studies on mouse sensory neurons in cell
      cultures equipped with stimulating electrodes show that specific genes can be
      regulated by different patterns of action potentials, and that the temporal
      dynamics of intracellular signalling cascades are critical in decoding and
      integrating information contained in the pattern of neural impulse activity.
      Functional consequences include effects on neurite outgrowth, cell adhesion,
      synaptic plasticity and axon-glial interactions. Signalling pathways involving
      Ca2+, CaM KII, MAPK and CREB are particularly important in coupling action
      potential firing to the transcriptional regulation of both neurons and glia, and
      in the conversion of short-term to long-term memory. Action potentials activate
      multiple convergent and divergent pathways, and the complex network properties of
      intracellular signalling and transcriptional regulatory mechanisms contribute to
      spike frequency decoding.

PMID- 11529311
TI  - Efficiency and complexity in neural coding.
AB  - Neural coding in the retina and lamina of fly compound eyes is amenable to
      detailed anatomical, physiological and theoretical analysis. This approach shows
      how identified cell signalling systems are optimized to maximize the transmission
      of information. Optimization reveals three familiar constraints, noise,
      saturation and bandwidth, and shows how coding can minimize their effects.
      Experiments reveal a fourth constraint, metabolic cost, whose properties favour
      the distribution of information among multiple pathways. The advantages of
      distributed codes will be offset by increasing complexity and the build up of
      noise. The optimization of coding in fly retina suggests that both noise and
      complexity will be reduced by matching each step in the system's operations to
      the input signal, and to the logical requirements of the network's ultimate
      function, pattern processing. This line of argument suggests tightly organized
      networks, laid out that information flows freely and independently, yet patterned
      so that the necessary contacts and transactions are made quickly and efficiently.

PMID- 11529313
TI  - Predictive learning of temporal sequences in recurrent neocortical circuits.
AB  - When a spike is initiated near the soma of a cortical pyramidal neuron, it may
      back-propagate up dendrites toward distal synapses, where strong depolarization
      can trigger spike-timing dependent Hebbian plasticity at recently activated
      synapses. We show that (a) these mechanisms can implement a temporal-difference
      algorithm for sequence learning, and (b) a population of recurrently connected
      neurons with this form of synaptic plasticity can learn to predict spatiotemporal
      input patterns. Using biophysical simulations, we demonstrate that a network of
      cortical neurons can develop direction selectivity similar to that observed in
      complex cells in alert monkey visual cortex as a consequence of learning to
      predict moving stimuli.

PMID- 11529312
TI  - Neural dynamics in cortical networks--precision of joint-spiking events.
AB  - Electrophysiological studies of cortical function on the basis of multiple single
      neuron recordings reveal neuronal interactions which depend on stimulus context
      and behavioural events. These interactions exhibit dynamics on different time
      scales, with time constants down to the millisecond range. Mechanisms underlying
      such dynamic organization of the cortical network were investigated by
      experimental and theoretical approaches. We review some recent results from these
      studies, concentrating on the occurrence of precise joint-spiking events in
      cortical activity, both in physiological and in model neural networks. These
      findings suggest that a combinatorial neural code, based on rapid associations of
      groups of neurons co-ordinating their activity at the single spike level, is
      biologically feasible.

PMID- 11529314
TI  - Controlling the immune system: diffuse feedback via a diffuse informational
      network.
AB  - Diffuse feedback is defined to be a process by which a system in some sense
      improves its performance with respect to a variety of conflicting and even
      contradictory goals. In the immune system, such feedback is mediated by scores of
      extracellular chemicals (cytokines), each of which participates in achieving
      several goals. Progress toward any given goal is mediated by several cytokines.
      The 'immunoinformatics' of this diffuse informational network will be discussed.
      It will be shown how diffuse feedbacks, based on this network, can improve the
      performance of a given type of immune effector cell, and can cause the
      preferential amplification of more potent effectors. It will be argued that
      diffuse feedback also acts in other biological systems ranging from the metabolic
      system to ant colonies.

PMID- 11529315
TI  - Functional modules in biological signalling networks.
AB  - Signalling pathways carry information from the outside of the cell to cellular
      machinery capable of producing biochemical or physiological responses. Although
      linear signalling plays an important role in biological regulation, signalling
      pathways are often interconnected to form networks. We have used computational
      analysis to study emergent properties of simple networks that consist of up to
      four pathways, We find that when one pathway gates signal flow through other
      pathways which produce physiological responses, gating results in signal
      prolongation such that the signal may be consolidated into a physiological
      response. When two pathways combine to form a feedback loop such feedback loops
      can exhibit bistability. Negative regulators of the loop can serve as the locus
      for flexibility whereby the system has the capability of switching states or
      functioning as a proportional read-out system. Networks where bistable feedback
      loops are connected to gates can lead to persistent signal activation at distal
      locations. These emergent properties indicate system analysis of signalling
      networks may be useful in understanding higher-order biological functions.

PMID- 11529316
TI  - The versatility and complexity of calcium signalling.
AB  - Ca2+ is a universal second messenger used to regulate a wide range of cellular
      processes such as fertilization, proliferation, contraction, secretion, learning
      and memory. Cells derive signal Ca2+ from both internal and external sources. The
      Ca2+ flowing through these channels constitute the elementary events of Ca2+
      signalling. Ca2+ can act within milliseconds in highly localized regions or it
      can act much more slowly as a global wave that spreads the signal throughout the
      cell. Various pumps and exchangers are responsible for returning the elevated
      levels of Ca2+ back to the resting state. The mitochondrion also plays a critical
      role in that it helps the recovery process by taking Ca2+ up from the cytoplasm.
      Alterations in the ebb and flow of Ca2+ through the mitochondria can lead to cell
      death. A good example of the complexity of Ca2+ signalling is its role in
      regulating cell proliferation, such as the activation of lymphocytes. The Ca2+
      signal needs to be present for over two hours and this prolonged period of
      signalling depends upon the entry of external Ca2+ through a process of
      capacitative Ca2+ entry. The Ca2+ signal stimulates gene transcription and thus
      initiates the cell cycle processes that culminate in cell division.

PMID- 11529317
TI  - Multiple pathways of ERK activation by G protein-coupled receptors.
AB  - It has only recently been fully realized that G protein-coupled receptors and G
      proteins play crucial roles in the regulation of cell growth, differentiation and
      even tumour formation. Naturally occurring mutations in G protein-coupled
      receptors and in G protein alpha subunits result in uncontrolled cellular
      proliferation resulting in distinct human diseases. One important mechanism to
      transduce mitogenic signals from the cell membrane to the cell nucleus is the
      engagement of the extracellular signal-regulated kinase (ERK)-mitogen-activated
      protein kinase (MAPK) cascade. A multitude of distinct signal transduction
      pathways have been deciphered which connect G proteins with the ERK cascade. Both
      receptor and non-receptor tyrosine kinases play pivotal roles in these signalling
      pathways. Mitogenic signalling by G protein-coupled receptors can be regarded as
      a complex interplay between signals emanating from different classes of cell
      surface receptors which ultimately converge upon a small subset of central
      signalling proteins in the cell. The characterization of receptor-, G protein-
      and tyrosine kinase-specific contributions to mitogenic signalling in a
      particular cell and the identification of proteins serving as a point of
      convergence in the mitogenic signalling cascade may ultimately allow the design
      of novel pharmacological approaches to treat diseases involving unrestricted cell
      proliferation.

PMID- 11529318
TI  - Heterogeneity of second messenger levels in living cells.
AB  - Over the last years we have utilised chimeras from aequorin and green fluorescent
      protein (GFP) to monitor the dynamics of second messenger levels in living cells.
      In this contribution we address two problems, i.e. the complexity of Ca2+
      handling by mitochondria and the localization of cAMP signalling. As to the
      first, we here demonstrate that physiological increases in mitochondrial Ca2+,
      monitored with selectively localized recombinant aequorin, concern a sub
      population of organelles that is stably and selectively associated with the
      endoplasmic reticulum. As to cAMP, we describe the use of a novel probe to
      monitor its changes in living cells, that takes advantage of the phenomenon of
      fluorescence resonance energy transfer (FRET) between suitable GFPs linked to the
      regulatory and catalytic subunits of protein kinase A (PKA). When cAMP is low the
      two fluorophores are in close proximity and generate FRET while increasing levels
      of cAMP determine progressive reduction of FRET as the two subunits (linked to
      the GFPs) diffuse apart. We also demonstrate that by using such cAMP sensor,
      localized increase of this second messenger can be observed upon selective
      stimulation of plasma membrane receptors.

PMID- 11529319
TI  - Humoral coding and decoding.
AB  - Humoral communication systems are dynamically regulated. Most hormones are
      released in a pulsatile or burst-like manner into the bloodstream. It is well
      known that information coded in the frequency and amplitude of secretory pulses
      allows for the differential regulation of specific target cell function and
      structure. However, despite intensive study of transmembrane signalling
      relatively little is known about how the temporal dynamics of extracellular
      humoral stimuli specifically regulates the temporal pattern of intracellular
      signalling pathways, such as Ca2+-dependent signalling. Repetitive spikes of Ca2+
      encode this information in their amplitude, duration and frequency, and are in
      turn decoded into the pattern of gene expression and phosphorylation of target
      proteins. Using a mathematical model for G protein-coupled Ca2+ signalling and
      information-theoretic approaches to stimulus reconstruction we have
      systematically quantified the amount of information coded in the Ca2+-signal
      about the dynamics of the stimulus, which allows us to explore the temporal
      bandwidth of transmembrane signalling. These in silico approaches permit us to
      differentiate the amount of information coded in the frequency, temporal
      precision, amplitude and the complete Ca2+-signal. This may open an avenue to the
      quantification of information flow and processing in the intra- and intercellular
      coding and decoding machinery.

PMID- 11529320
TI  - Update on HIV/AIDS in Thailand.
AB  - Thailand experienced its first case of AIDS in 1984. Approximately 800,000 Thais
      were infected with HIV in 1995 and 1 million Thais became infected by the year
      2000. There have been 5 major epidemic waves: among male homosexuals (started
      1984-5), intravenous drug users (started 1988), female commercial sex workers
      (started 1989), male clients (started 1990), and housewives and the newborn
      (started 1991). Approximately 96 per cent of HIV-1 infected Thais carried
      recombinant subtype A/E, the rest carried B'. In a male seroconvertors cohort of
      235 cases, median time to show CD4 <200 cells/microL was 6.8 years. Five years
      survival was significantly lower than that of the other subtype B seroconvertors
      study, i.e., 82 per cent compared to 90 per cent. Interestingly, 13.5 per cent of
      seronegative Thais showed homozygous SDF1-3'A polymorphism, which suggests that
      approximately one-tenth of Thais may become long-term non-progressors after HIV-1
      infection. Primary HIV infection syndrome is rare among Thai patients (1.1%). In
      contrast, it was 50-90 per cent in Western cohorts. In early symptomatic
      patients, one-third developed pruritic pappular eruptions (PPEs). In advanced
      stage, disseminated tuberculosis, Pneumocystis carinii pneumonia (PCP),
      cryptococcosis, and esophageal candidiasis are commonly found. In Northern
      Thailand, however, Penicillium marneffei infection or penicillosis is more common
      than cryptococcosis. The recent understanding of HIV pathogenesis suggests that
      HIV eradication is unlikely to be achievable with current strategies. Several
      National HIV treatment guidelines including the Thai guideline have been
      recommended treatment with triple antiretroviral regimen when patients become
      symptomatics or CD4+ <200. Current development of antiretroviral therapy which
      includes new agents, new formulas, and pharmacokinetic enhancements, is directed
      to better potency, higher genetic resistant barrier, less pill burden, and once a
      day dosing. These will ultimately improve the adherence and the long-term
      effectiveness of antiretroviral treatment. In reality, however, although the cost
      of triple regimen is dramatically declining, many patients still can not afford
      it. Primary prophylaxis and early diagnosis and treatment of opportunistic
      infection should be considered in patients with CD4+ <200 cells/microL. Modified
      short course ZDV studies and donation campaigns for preventing mother-to-child
      transmission, clinical trials to investigate the best use of expensive anti HIV
      medications in a poor resource setting have been or are being conducted. Nine
      phase I/II HIV-1 vaccine trial protocols have been or are being tested. A phase
      III trial of gp120 subtype B/E (AIDSVAX, VaxGen) was started in 1999, a total of
      2,500 volunteers will be enrolled, and interim analysis is planned for August
      2002. Thai investigators are also participating in pre-clinical development of
      recombinant BCG and DNA vaccines. Multidisciplinary and multi-level approaches,
      both by the government and private sectors, have had a positive impact on the HIV
      epidemic as shown by the declining seroprevalence of HIV infection in Thai male
      conscripts, and of major sexually transmitted diseases in men. Nevertheless, more
      effort at the grass roots level is needed to ensure further success and
      sustainability of the control of the HIV epidemic in Thailand.

PMID- 11529321
TI  - Scurvy: a case report.
AB  - An 8-year-old child with cerebral palsy came with progressive purpuric rash
      affecting the trunk and legs. He had tenderness on palpation of his extremities.
      Physical examination revealed a moderately pale and cachectic boy. There was
      bleeding per swollen gums and petichiae on the hard palate. Generalized multiple
      discrete palpable petichiae spots at hair follicles along the whole body, more on
      both legs, were observed. He also had tenderness on palpation of his extremities.
      His hemoglobin was 6.6 g/dl. Platelet count and coagulogram were normal.
      Roentgenographic findings showed generalized osteoporosis, metaphyseal white line
      of distal femur, proximal tibia. proximal fibula, distal radius, and distal ulna
      with submetaphyseal lucency bilaterally. Skin biopsy showed dilated hair
      follicles, filled with keratinous material and a small corkscrew hair. A
      diagnosis of scurvy was made; and vitamin C at a dosage of 300 mg per day was
      given. His swollen gums, bleeding per gums and muscle tenderness improved within
      2 days. Perifollicular hemorrhage, follicular hyperkeratosis, and anemia improved
      in 2 and 3 weeks respectively.

PMID- 11529322
TI  - Complete heart block in children at King Chulalongkorn Memorial Hospital.
AB  - The etiologies of complete heart block in thirty-one children (mean age 5.5 +/-
      5.2 years, range 0-14 years) diagnosed at King Chulalongkorn Memorial Hospital
      between 1990-2001 were reviewed. Three main groups of patients were identified:
      1) patients who presented in utero or in the newborn period (congenital heart
      block, n = 6), 2) patients who had complete heart block after cardiac surgery
      (postoperative heart block, n = 10), and 3) children outside the newborn period
      with a new diagnosis of complete heart block unrelated to cardiac surgery
      (unknown etiology, n = 15). Among 15 patients in the last group, 5 were
      asymptomatic (or minimally symptomatic) with complete heart block unexpectedly
      found. These patients probably had previously undetected congenital heart block.
      Two patients had complete heart block associated with mild viral illness, but no
      bradycardia-related symptom. The etiology for heart block in these 2 patients was
      unknown. Eight patients probably had recent onset heart block because of new
      bradycardia-related symptoms, or a previously documented normal heart rate. All
      patients in this group were female (mean age 4.3 +/- 4.3 years, median 3.5
      years). All were diagnosed between August and January, and the majority (75%) had
      a history of non-specific viral illness in the preceding 2 weeks. Seven patients
      (87.5%) were acutely symptomatic. Syncope and/or seizure were the most common
      presenting symptoms. Left ventricular systolic dysfunction was found in only one
      patient. The etiology of complete heart block in these patients probably was an
      acute viral myocarditis that preferentially affected the conduction system. Two
      of these eight patients had complete recovery of the atrioventricular conduction.
      The rest had no improvement or had only partial recovery and subsequently
      underwent permanent cardiac pacemaker insertion.

PMID- 11529323
TI  - Epidemiological survey of mental disorders and knowledge attitude practice upon
      mental health among people in Bangkok Metropolis.
AB  - To find the prevalence of 8 mental disorders and study knowledge, attitude,
      practice (KAP) upon mental health among people in Bangkok Metropolis a cross
      sectional, descriptive community survey was conducted. Two thousand, nine hundred
      and forty eight samples aged 15-60 years were selected by a multistage simple
      random sampling technique. Data collection was made by qualified interviewers who
      had experience in mental health care and had been trained to use the
      questionaires. The questionaires had been modified from DSM-IV and CIDI that had
      been tested for good validity and reliability. The survey methodology was divided
      into 2 stages, screening and diagnosis. The results showed that the life time
      prevalence of mental disorders were; schizophrenia (1.3%), mood disorders; manic
      episode (9.3%), major depressive episode (19.9%), dysthymia (1%), anxiety
      disorders (10.2%), mental retardation (1.8%), epilepsy (1.3%), suicidal idea
      (7.1%), drug and substances use disorders (11.2%), and alcohol use disorders
      (18.4%). Knowledge score was good, attitude was fairly good, practice was still
      weak in promotion and prevention aspects. As such, this study was used as a
      pattern to conduct a national survey in 14 provinces all over Thailand and the
      results are being summarized. The information is similar to the Global Burden of
      Diseases. We produced a national training program on "Detection and Management of
      Depression" for Primary Care Physicians that was, a 2 days' workshop. Other
      national programs promoting prevention and control have also been set up.

PMID- 11529324
TI  - Primary conjunctival tuberculoma: a case report.
AB  - Conjunctival tuberculoma is very rare in modern medicine. We report a case of a
      34-year-old Thai female patient presenting with multiple peculiar conjunctival
      nodules. Two small nodules were excised and submitted for histopathological
      study, which showed discrete granulomatous inflammation with caseating necrosis.
      The acid-fast bacilli's staining for tuberculous bacteria was positive. There was
      no other organ involvement of active tuberculosis. The patient was then treated
      with systemic anti-tuberculous regimen for 6 months. The remaining lesions
      disappeared within the first few months of treatment. Conjunctival tuberculoma
      should always be considered in cases of conjunctival nodules.

PMID- 11529325
TI  - Ice test for ocular myasthenia gravis.
AB  - A prospective, non randomized comparative study was conducted to examine the
      efficacy of the ice test in differentiating myasthenia gravis (MG) ptosis from
      non MG. Twenty patients with MG ptosis and 20 with non MG ptosis were evaluated
      by measuring the palpebral fissures pre and post ice test applied on the eyelids
      for 2 minutes. The difference in widening of palpebral fissure 2 mm or more was
      considered as a positive ice test. The results showed that 19 from 20 MG patients
      had positive ice test, whereas, all non MG patients had negative results. The
      sensitivity and specificity of the test were 95.0 per cent and 100 per cent,
      respectively while the accuracy or efficacy of the test was 97.5 per cent. In
      conclusion, the ice test is a useful, simple, safe, fast, cheap, and easy to
      perform for the screening and diagnosis MG patients with ocular ptosis.

PMID- 11529326
TI  - Optic nerve glioma in infancy: a case report of the youngest patient in Thailand.
AB  - A 4-month-old infant came to the department of Ophthalmology, King Chulalongkorn
      Memorial Hospital with right eye proptosis, strabismus, and no vision. She was
      diagnosed as optic nerve and chiasm glioma. The subtotal removal of the tumor was
      performed and followed by chemotherapy, with a satisfactory result. Because of
      the large size of the tumor and the presenting symptoms and signs since the
      patient was only 2 month old, we believe that this tumor originated in the
      intrauterine period. To our knowledge, this reported case is the youngest patient
      with optic nerve and chiasm astrocytoma in Thailand.

PMID- 11529327
TI  - Treatment of cytomegalovirus retinitis in acquired immunodeficiency syndrome with
      intravitreal ganciclovir implant.
AB  - To determine the efficacy and complication of the sustained-release intravitreal
      ganciclovir implanted to control cytomegalovirus (CMV) retinitis in acquired
      immunodeficiency syndrome (AIDS) patients, a prospective study with intravitreal
      ganciclovir devices placed in 5 eyes was conducted. No concomitant systemic anti
      CMV therapy was used. The results showed that retinitis was controlled in all
      cases. Visual acuity improved dramatically within three weeks postoperatively and
      maintained for a mean period of 5.6 months. The best corrected postoperative
      visual acuity of the groups was not statistically significantly different from
      the preoperative measurement, (P=0.06, one-tailed test). Serious ocular
      complications were not encountered. As such the implant offers a promising
      alternative for local control of CMV retinitis associated with AIDS. The vision
      was improved and stabilized with functional vision.

PMID- 11529328
TI  - Detection of dengue HI and IgM antibody: is it diagnostically useful? when and
      how?
AB  - The incidence of dengue infection at King Chulalongkorn Memorial Hospital from
      1997 to 2000 was reviewed from laboratory information. The highest incidence of
      the disease occurred from the rainy season to the winter. Most cases were aged
      below 15 years (87.89%) and no sexual preponderance was observed. The majority of
      cases were secondary infection (62.09%). Detection of HI titer is still useful
      for diagnosis although paired serum has to be taken. The time interval between
      sera should be at least 7 days for suspected primary infection but a shorter time
      interval can be considered for suspected secondary cases. Rapid and accurate
      detection of dengue IgM has become more useful because only single serum is
      required. A request for dengue IgM should be done after day 5 of illness.
      However, interpretation of the result should be done carefully according to the
      timing of serum collection.

PMID- 11529329
TI  - Feasibility study on the detection of ferritin using surface plasmon resonance.
AB  - Determination of ferritin concentration was performed using surface plasmon
      resonance technique. An anti-human ferritin antiserum from rabbits was
      immobilized on the protein-A coated sensor chip. The resonance change due to the
      binding of ferritin to the antibody was measured. It was found that the antigen
      antibody binding of the ferritin could be monitored in real time. The detection
      of ferritin could be obtained in the range of 25-800 ng/ml. This dynamic range
      could be applied in various medical applications. Moreover, it was observed that
      the sensor chips could be regenerated. This offers an opportunity for multiple
      uses, which will reduce the unit operating cost.

PMID- 11529330
TI  - Potassium status of Northeast Thai constructors in three different geographic
      locations.
AB  - Sudden and unexpected death of young adults during sleep is a phenomenon among
      Southeast Asians and particularly young Northeast (NE) Thailand constructors in
      Singapore. Survivor of sudden unexplained death syndrome (SUDS) without
      structural heart disease with idopathic ventricular fibrillation (VF) has been
      documented. Low plasma potassium (K) and depletion of K can occur simply through
      a reduction of K intake and are associated with increased risk of VF. The K
      status of the populations was evaluated in the NE (Group 1, n=30), Bangkok (Group
      2, n=48) and Singapore (Group 3, n=46). Groups 2 and 3 were further subdivided
      into Group 2A (worked in Bangkok < or = 1 year, n=8), Group 2B (worked in Bangkok
      > 1 year, n=40), Group 3A (consumed self-prepared or ready-to-buy meals, n=25)
      and Group 3B (regularly consumed foods provided free-of-charge by construction
      companies, n=21). Thirty-four male healthy university personnels from the NE and
      Bangkok served as the control--Group 4. Two 24-h urine samples and a fasting
      blood sample were collected from each subject. Dietary-K from food was determined
      by duplicated meal analysis. All these samples were then analyzed for their K
      content. Group 3A had the lowest K-status: their K-intake, serum-K, and urinary-K
      level were 29 +/- 5.8 mmol/day (% low K-intake=100), 3.43 +/- 0.34 mmol/L (%
      hypokalemia=48) and 19.23 +/- 8.2 mmol/day (% hypokaliuria=87.5), respectively.
      Among the construction workers, average K-intake, serum-K and urinary-K levels
      were 45.5 +/- 6.1 mmol/day (% low K-intake = 37.5), 3.93 +/- 0.2 mmol/L (%
      hypokalemia = 2.5) and 39.6 +/- 9.2 mmol/day (% hypokaliuria = 12.5),
      respectively. The values of Group 2B were similar to Group 4. In addition, when
      the data from all of the groups were compared, there was a positive correlation
      between dietary-K (intake) and urinary-K (excretion) (r=0.881, p<0.001). In
      conclusion, NE Thailand constructors from various locations exhibited low K
      status with low dietary-K, high incidence of hypokalemia, and low urinary-K. From
      the present study, this low K status may be an important trigger factor for VF in
      construction workers and associated with increase risk of SUDS.

PMID- 11529331
TI  - Specific IgE antibody responses to somatic and excretory-secretory antigens of
      third stage G. spinigerum larvae in human gnathostomiasis.
AB  - Specific IgE antibody levels in the serum of patients with proven gnathostomiasis
      and in those with intermittent cutaneous migratory swelling (CMS) were determined
      by the enzyme-linked immunosorbent assay (ELISA) using somatic extract and
      excretory-secretory (ES) products of Gnathostoma spinigerum infective larvae as
      antigens. The third stage larval used were obtained from naturally infected eels.
      There was an increase in specific IgE antibody to both antigens in these
      patients. The mean levels of these specific IgE antibodies were significantly
      higher than that of the healthy control (P<0.01). Comparison between using
      somatic extract and ES products in the test showed, a positive result in the
      group of suspected patients with gnathostomiasis or CMS was significantly higher
      when using ES products (81.81%) than somatic extract (59.09%) as the antigens
      (P<0.05). However, both somatic and ES antigens cross-reacted with other
      parasitic sera. The overall sensitivity of the ELISA for these IgE antibodies
      detection were 71.87 per cent and 87.50 per cent with somatic and ES antigens,
      respectively. The specificity was 57.53 per cent when somatic antigen was used
      and increased to 69.86 per cent when ES antigen was used. The positive and
      negative predictive values of the test were 42.59 per cent and 82.35 per cent by
      using somatic antigen. Both of these values, were also increased to 56.00 per
      cent and 92.72 per cent by using the ES antigen. It is obvious that more
      potential components may be present in ES products than those in the somatic
      extract. The ES antigen may have to be further purified and may be suitable for
      evaluation of the effectiveness of chemotherapy. As such, the antibody responses
      to secreted products are more closely related to active infection than the anti
      whole worm antibody that may persist following the death of the parasites.
      However, in this disease, the effect of the IgE antibody on its pathophysiology
      it is still not known.

PMID- 11529332
TI  - Problems and prevention of viral hepatitis in Thailand.
AB  - To this day, viral hepatitis remains a major public health problem in Thailand.
      Chronic infection with hepatitis B and C viruses are the leading causes of
      chronic liver diseases, including cirrhosis and hepatocellular carcinoma (HCC).
      Outbreaks of hepatitis A virus continue to occur in Thailand, even after several
      years of consistently declining prevalence rates. Also, the reduction in
      prevalence of hepatitis D virus infection has been observed among intravenous
      drug users over the past decade. Hepatitis E virus constitutes a rather unusual
      cause of sporadic acute hepatitis in Thailand. Highly effective vaccines are
      currently available for prevention of hepatitis A and B, however, as yet no
      effective vaccine for hepatitis C is imminent. Following rapid progress in the
      development of molecular techniques, several new hepatitis viruses have been
      identified. Among these, Hepatitis G, TT and SEN viruses have recently been
      described but their significance as to causation of human liver disease has yet
      to be established. This article reviews the current epidemiology, molecular
      biology, and strategies aimed at prevention and control of hepatitis virus
      infection in Thailand emphasizing new developments and recent data obtained from
      our research studies.

PMID- 11529333
TI  - Lymphatic filariasis caused by Brugia malayi in an endemic area of Narathiwat
      Province, southern of Thailand.
AB  - Lymphatic filariasis caused by Brugia malayi is highly prevalent in Narathiwat
      province of Thailand. The World Health Organization has aimed to eliminate the
      disease globally by the year 2020. To achieve the goal, assessment of the real
      disease situation should be integrated as part of the control program. The
      preliminary data for long-term study of the disease situation in this endemic
      area is necessary for the elimination program of lymphatic filariasis. By using
      the conventional microscopic method, the microfilarial rate of B. malayi in an
      endemic area of Narathiwat province was 1.38 per cent. The microfilarial
      densities ranged from 17 microfilariae/ml to 1,250 microfilariae/ml median = 50.
      The highest prevalence was found in the age group > 45-60 (4.69%). The lowest
      microfilarial rate was in the age group < or = 15 (0.37%). The infection in males
      was about three fold the number in females. A PCR-based method was employed to
      detect a B. malayi-specific Hha I repetitive DNA sequence with high specificity
      and sensitivity. The PCR assay will be useful in assisting the elimination
      program of lymphatic filariasis in control and monitoring the disease in
      Thailand.

PMID- 11529334
TI  - Caffeine clearance in patients with chronic viral hepatitis: before and after
      interferon therapy.
AB  - The purpose of this study was to evaluate caffeine clearance, a quantitative
      measurement of metabolizing capacity of the liver, in chronic hepatitis B and C
      before and after interferon treatment. Biochemical test using AST and ALT,
      virological test, and caffeine clearance were measured in eighteen patients with
      chronic hepatitis B and five patients with chronic hepatitis C at pre and post
      treatment with interferon. Caffeine clearance was determined in each patient
      using two point analysis following a 3.5 mg/kg oral administration of caffeine
      solution. Blood samples were subsequently collected at 12 and 16 hours after
      caffeine administration and assayed for serum caffeine level by HPLC technique.
      Clearance was calculated using the equation of Cl = Kel x Vd. It was found that
      caffeine clearances determined before and after interferon treatment were not
      significantly different in both chronic hepatitis B and C inspite of biochemical
      and virological responses after therapy. Caffeine clearance change in two
      diffferent groups of chronic hepatitis B defined as biochemical response and
      nonresponse were compared. Although caffeine clearance change between responders
      and nonresponders to interferon treatment was not significantly different, it
      tended to increase in those patients who had biochemical response to interferon.
      It appeared that metabolic capacity of the liver does not change with interferon
      therapy inspite of biochemical and virological responses.

PMID- 11529335
TI  - Effects of Russell's viper venom on mediator production in cultured human
      umbilical vein endothelial cells.
AB  - Hemodynamic alterations in Russell's viper envenomation are the result of
      interactions of various vasoactive mediators and perhaps proinflammatory
      cytokines. Since vascular endothelium is likely to be exposed to high
      concentrations of the venom and the endothelial cell itself not only plays an
      important role in the physiologic control of the circulation, but also play a
      role in inflammation with the synthesis and secretion of proinflammatory
      cytokines. It was therefore, the objective of this study to determine the effects
      of Russell's viper venom (RVV) on proinflammatory cytokine production by cultured
      human umbilical vein endothelial cells (HUVEC) and the release of endothelium
      derived substances. Endothelial cells were isolated from freshly obtained human
      umbilical cord vein and grown in tissue culture to confluence as a homogeneous
      population. Cells were then incubated at 37 degrees C under 5 per cent CO2 with
      RVV (0.2, 1.0, 5.0, and 25.0 microg/ml) or lipopolysaccharide (LPS, 10 microg/ml)
      for 3, 6, 12 and 24 hours. After an indicated time, the levels of endothelin-1
      (ET-1); 6-keto-PGF1alpha (a stable metabolite of PGI2) tumor necrosis factor
      alpha (TNF-alpha); interleukin-1beta (IL-1beta); and interleukin-6 (IL-6) in
      supernatants were measured by using ELISA or EIA. The effect of RVV or LPS on
      cell viability was also measured using MIT assay. The results showed copious
      amounts of ET-1 production irrespectively with the presence of RVV or LPS.
      Whereas, production of PGI2 (measured as 6-keto-PGF1alpha, a stable metabolite)
      was increased significantly higher in the RVV- and LPS-treated EC than in the
      control EC. However, TNF-alpha and IL-6 productions were not different among
      these groups. The levels of IL-1beta were very low, although IL-1beta was
      detectable in the group treated with RVV at a concentration of 25.0 microg/ml. In
      conclusion, RVV upto 25 microg/ml stimulated PGI2 production by cultured HUVEC.
      This effect was unlikely related to production of proinflammatory cytokines since
      LPS or RVV is not sufficient per se to elevate a substantial amount of EC-derived
      cytokines. The higher amount of IL-6 compared to TNF-alpha and IL-1beta may be
      produced through other pathways apart from production via a cascade of cytokines.
      This is the first report showing that RVV up to 25 microg/ml has no effect on
      prominent proinflammatory cytokine production by HUVEC. However, in blood
      circulation, the major source of cytokines production is monocyte-macrophage
      lineage cell. Thus, RVV in blood circulation may activate the production of
      proinflammatory cytokines mainly from those cells and subsequently induce
      toxicity.

PMID- 11529336
TI  - Relaxant effect of 6-deoxyclitoriacetal on smooth muscle preparations.
AB  - The pharmacological effect of 6-deoxyclitoriacetal (6-DA), a rotenoid compound
      isolated from the roots of Clitoria macrophylla Wall. (Papilionaceae), was
      examined on different smooth muscle preparations. 6-Deoxyclitoriacetal 0.2 mg/ml
      produced a significant decrease in the spontaneous contraction of isolated rat
      uterus. It also suppressed the contraction induced by acetylcholine 5x10(-6) M
      and oxytocin 5x10(-3) IU/ml. The cumulative contractile responses of rat aortic
      strips caused by serotonin 10(-8)-10(-4) M and norepinephrine 10(-11)-10(-7) M
      were reduced by 6-DA 0.4 mg/ml. In calcium free Kreb's solution, 6-DA inhibited
      the aortic contraction produced by a cumulative dose of calcium chloride (0.1-30
      mM). In guinea-pig ileum, 6-DA 0.15 mg/ml exerted the spasmolytic activity by
      inhibition of the contractile response evoked by various contractile agents e.g.
      acetylcholine 10(-9)-10(-5) M, serotonin 10(-9)-10(-5) M and histamine 10(-9)-10(
      5) M. All of the results indicated that 6-DA could induce a smooth muscle
      relaxant effect by interference with intracellular calcium metabolism.

PMID- 11529337
TI  - Results of radiation therapy in stage 1B cervical carcinoma at King Chulalongkorn
      Memorial Hospital: fifteen-year experience.
AB  - A retrospective study was performed on 131 patients with stage 1B cervical
      carcinoma who were referred and treated with external beam radiation and
      intracavitary brachytherapy at the Division of Radiation Therapy, Department of
      Radiology, King Chulalongkorn Memorial Hospital between February 1985 and
      February 2000. Primary outcomes were overall survival rate, progression free
      survival rate, recurrence, and treatment-related complications. The treatment
      results from different sources of intracavitary radiation therapy were secondary
      endpoints. The number of patients treated with Ra-226, Cs-137, and Ir-192
      intracavitary irradiation were 12, 84, and 35 patients respectively. The median
      follow-up times were 69, 59, and 21 months for Ra-226, Cs-137, and Ir-192,
      respectively. Actuarial 5-year overall survival rate was 89 per cent. The 5-year
      progression free survival rate was 80 per cent. Actuarial 5-year survival and
      progression free survival rate were comparable among different sources of
      intracavitary brachytherapy (p = 0.553 and p=0.793, respectively). The overall
      recurrent rate was 16.8 per cent. Of the recurrence; 40.9 per cent was
      locoregional, 54.6 per cent was distant failure, and 4.5 per cent was combined
      locoregional and distant failure. The overall complication rate was 25.95 per
      cent. The severe complication rates (Grade III-V) from treatment occurred in the
      urinary bladder (0.76%) and in the small bowel (0.76%.) These results suggest
      that radiation therapy alone is an effective treatment for stage 1B cervical
      carcinoma. Additionally, all types of intracavitary brachytherapy provide
      comparable clinical results.

PMID- 11529338
TI  - Intracranial lymphoma: CT and MR findings.
AB  - The purposes of the present study were to describe CT and MR findings of
      intracranial lymphoma, to define imaging characteristics of primary and secondary
      intracranial lymphomas, and to compare CT and MR findings in the same patients.
      CT and MR studies of 26 patients with the diagnosis of intracranial lymphoma at
      King Chulalongkorn Memorial Hospital from 1988 to 2000 were reviewed. There were
      22 cases of primary lymphoma (21 non-AIDS and 1 AIDS) and 4 cases of secondary
      lymphoma. Fifty-eight lesions were found. In primary lymphoma, most lesions were
      in the periventricular areas, appearing as multiple large well-defined margin
      masses with minimal surrounding edema and dense homogeneous enhancement on both
      CT and MR studies. The masses were hyperdense on CT scan, isointense on T1W
      images, and hyperintense to gray matter on T2W MR images. In one AIDS patient,
      rim enhancement of the lesion was found. Other uncommon findings included
      intratumoral hemorrhage, isolated mass in the brain stem and extracerebral
      locations. In secondary lymphoma, smaller and more lesions were noted. Diffuse
      ependymal enhancement was demonstrated in one case. The results suggest that MRI
      is more sensitive than CT scan in detecting intracranial lesions of lymphoma.

PMID- 11529339
TI  - Intubating conditions after three different doses of rocuronium in the elderly.
AB  - This randomized controlled trial study evaluated the intubating conditions at 1
      minute after 0.3, 0.6 and 0.9 mg/kg of rocuronium in 60 Thai elderly patients who
      enrolled for elective surgery under general anesthesia with fentanyl, thiopental
      and halothane at King Chulalongkorn Memorial Hospital. Excellent or good
      conditions were observed in 50 per cent (p<0.05) at rocuronium 0.3 mg/kg,
      compared with 95 and 85 per cent at 0.6 and 0.9 mg/kg of rocuronium, respectively
      but the excellent conditions were 5 (p<0.05), 30 and 45 per cent from each dose.
      Therefore, rocuronium 0.6 or 0.9 mg/kg should be adequate for intubation in
      elective, elderly patients but was inadequate for emergency case. In addition,
      rocuronium 0.3 mg/kg is insufficient for intubation at 1 minute in this age
      group. No serious side effects of the drug nor complications were found in this
      study.

PMID- 11529340
TI  - Learning manual skills in spinal anesthesia and orotracheal intubation: is there
      any recommended number of cases for anesthesia residency training program?
AB  - Wide variability exists in the number of anesthetic procedures to which
      anesthesia residents are exposed during their training. The number of attempts at
      various procedures before a trainee becomes proficient at performing each
      anesthetic procedure is not known. To determine the learning process of 150
      attempts of spinal anesthesia and 100 attempts of orotracheal intubation, the two
      most frequent anesthetic procedures, we evaluated 9 first-year anesthesia
      residents according to their rate of success or failure. The learning curves of
      both procedures revealed an initial rapid improvement of success during the first
      20 attempts. Spinal anesthesia was more difficult to learn (p=0.0002) but the
      learning curves of spinal anesthesia and orotracheal intubation reached a
      nondifferent high success rate of 82 per cent and 88.9 per cent respectively
      (p=0.13). According to this study the institutional recommended number of cases
      for spinal anesthesia and orotracheal intubation were 112 and 27 cases
      respectively.

PMID- 11529342
TI  - Endoscopy in HIV infected patients.
AB  - HIV is a very common infection in Thailand, affecting about one million of the
      population already, with 99,555 persons with full blown AIDS at the end of 1999.
      The first case of AIDS was reported in Thailand in 1984. Gastrointestinal
      involvement is very common, the commonest presentations are diarrhea, esophageal
      symptoms, hepatobiliary symptoms, and weight loss. When the CD4+ T cell count
      falls below 200, the body becomes highly susceptible to opportunistic infections
      and neoplasms. Almost all AIDS patients will have GI symptoms at sometime during
      the course of their illness. This is because the GI tract contains an abundant
      quantity of lymphoid tissue and is likely to function as a reservoir of HIV
      infection. In chronic diarrhea cases, apart from other investigations, small
      bowel biopsy and aspiration may help to find the cause. If oral candidiasis is
      present, one should keep HIV in mind and look for oral hairy leucoplakia,
      dysphagia and odynophagia as one-third of patients with AIDS will develop
      dysphagia or odynophagia in the course of their disease. Those with esophageal
      candidiasis will usually have oral candidiasis and odynophagia while 18 per cent
      of the patients will not have oral thrush. CMV esophagitis and HIV ulcer (or
      idiopathic oesophageal ulcer) are also common. Upper gastrointestinal endoscopy
      and biopsy are helpful in finding the exact cause of the oesophageal symptoms.
      Hepatobiliary manifestations are present with jaundice, hepatomegaly, and pain.
      ERCP is very helpful in diagnosing and classifying these conditions. Papillary
      stenosis and dominant biliary stricture can be treated by endoscopy but long term
      results are still poor due to late manifestation of these conditions.

PMID- 11529341
TI  - Hypotension in spinal anesthesia for cesarean section: a comparison of 0.5%
      hyperbaric bupivacaine and 5% hyperbaric lidocaine.
AB  - Hypotension is a common side effect associated with spinal anesthesia. However,
      there is no previous report comparing the incidence of hypotension between two
      commonly used local anesthetic agents, bupivacaine and lidocaine. The objective
      of this study was to compare the incidence of spinal hypotension induced by
      bupivacaine and lidocaine in parturients undergoing cesarean section. A double
      blind, randomized controlled trial was conducted in 142 parturients scheduled for
      cesarean section. The patients were randomized into two groups, 71 each. After
      receiving 10 ml/kg of normal saline intravenously, patients in the first group
      were given 2.2 ml of 0.5 per cent hyperbaric bupivacaine plus 0.2 mg of morphine
      as a spinal anesthetic agent while in the other group, 1.2 ml of 5 per cent
      hyperbaric lidocaine plus 0.1 mg of epinephrine and 0.2 mg of morphine were
      administered. Hypotension, defined as 30 per cent less systolic blood pressure
      than baseline value, was recorded and the patients were treated with 6 mg of
      ephedrine every 2 minutes until normotension was achieved. There was no
      statistically significant difference of incidence, onset, duration, and severity
      of hypotension between the two groups (p > 0.05). The amount of ephedrine used in
      both groups was also not significantly different. Late onset hypotension occurred
      after delivery (20-22 minutes after spinal anesthesia was performed) in 17
      patients (12%). As such, the rate of hypotension in lidocaine group was
      comparable to bupivacaine group. Delayed onset hypotension occurring after
      delivery was noted and these events have never been described. However, the
      mechanism of late onset hypotension remains unidentified. Thus, bupivacaine and
      lidocaine can be used interchangeably for spinal anesthesia for elective cesarean
      section without significant difference in the incidence of hypotension.

PMID- 11529343
TI  - Feasibility of urinary trans, trans-muconic acid determination using high
      performance liquid chromatography for biological monitoring of benzene exposure.
AB  - Benzene is an important carcinogenic substance used in many industrial processes.
      Inhalation of this substance can cause both acute and chronic toxicity. In this
      study, monitoring of benzene exposure by high-performance liquid chromatography
      (HPLC) for urine trans, trans-muconic acid (ttMA) determination was adapted. We
      described a new adapted sensitive and specific HPLC method. We mixed 0.5 mL of
      urine sample with 2 mL of Tris Buffer containing vanillic acid as internal
      standard (IS) and percolate this through a preconditioned ion-exchange column.
      After rinsing the column with phosphoric acid solution, acetate buffer, and
      deionized water, we eluated the analytes with 2 mL of an equivolume solution of
      1.5 mol/L sodium chloride and methanol. Of this, 10 microliter was injected into
      the HPLC column. The mobile phase consisted of, per liter, 10 ml of acetic acid,
      100 ml of methanol, and 5 mmol/L sodium acetate. The flow rate was started at 1.2
      ml/min. The ttMA and IS were detected at 4.2 to 4.4 and 12.6-13.3 minutes,
      respectively. The lowest detection limit was 0.05 mg/L.

PMID- 11529344
TI  - BMI and health risks of health checkup clients at the Preventive Medicine Clinic,
      King Chulalongkorn Memorial Hospital.
AB  - From August 1999 to June 2000, a cross-sectional analytic study was conducted in
      health check up clients to compare body mass index (BMI) and health risks data
      derived by measuring height, weight, and blood pressure, recording physical and
      laboratory outcome, and interviewing health characteristics. Data were analyzed
      for the relationships between BMI and lipids, and fasting blood sugar, and serum
      glutamate-pyruvate transaminase, and hemoglobin, and hypertension and other
      health risks and test for association by Chi-square test. The results showed that
      1350 health checkup clients were 25.8 per cent overweight and 7.3 per cent were
      obese. There was a gradient relationship of abnormal cholesterol levels (>300
      mg%) and levels of BMI. The abnormal triglyceride levels (>300 mg%) were higher
      in obesity than normal BMI (9.1% vs 1.6%). Hyperglycemia in obesity was higher
      than that of normal BMI (30.3% vs 11.6%). The percentage of two-fold abnormal
      SGPT levels (>76 units/L) in obesity (9.1%) was higher than that of normal BMI
      (2.8%). The percentage of anemia in underweight (28.3%) was higher than that of
      normal BMI (24.3%). Normal blood pressure in normal BMI (94.2%) was higher than
      that of obesity (69.7%).

PMID- 11529345
TI  - Survey of patterns, attitudes, and the general effects of exercise during
      pregnancy in 203 Thai pregnant women at King Chulalongkorn Memorial Hospital.
AB  - The patterns, attitudes, and general effects of exercise during pregnancy on the
      pregnancy outcome were retrospectively studied on a consecutive series of Thai
      pregnant women at the King Chulalongkorn Memorial Hospital between April and June
      2000. Two hundred and three postnatal patients were recruited and interviewed
      systematically. About 42.36 per cent of cases reported exercise while 57.64 per
      cent did not. The most common mode of exercise was walking, reported in 95.3 per
      cent and was most commonly performed in the afternoon (94.2%). The significant
      differences between the exercise and non-exercise group were income, education,
      occupation, some pregnant and neonatal outcomes. There was no significant
      difference in the occurrence of complications in both the exercise and non
      exercise groups. The studied subjects mostly felt that exercise could be done
      during pregnancy and believed that it produced benefits rather than harm.
      However, the proportion of the study group actually exercising was less than half
      and might be related to the infrequent advice given by obstetricians and nurses.
      To encourage proper exercise in pregnancy, all members of the related health care
      team should be involved closely in the planning.

PMID- 11529346
TI  - The anatomic basis of fasciocutaneous flap based on the posterior tibial vessels.
AB  - The skin of the medial aspect of the leg is supplied by the cutaneous perforating
      branches of the posterior tibial artery and can be raised as a flap based on the
      main artery or perforating branches. There are several studies regarding this
      vascular system but nothing about the true length of the perforating vessel has
      been mentioned. The present study was conducted in 20 cadaveric legs and the
      results showed that 1) The average diameters of perforators in the proximal,
      middle and distal thirds were 1.43, 1.20 and 1.12 mm respectively; 2) the average
      lengths were 35.11, 20.94 and 12.71 mm respectively; 3) the average location of
      the first branch was 7.35 cm from the tibial tubercle while the last branch
      resided 2.31 cm from the medial malleolus. This study provides some anatomical
      information, involving the vascular pedicle of the flap based on posterior tibial
      perforators, which could be beneficial in clinical practice.

PMID- 11529347
TI  - The combined external and intraoral approach: a new technique for mandibular
      angle resection.
AB  - To introduce a new technique for mandibular angle resection in facial esthetic
      surgery, a descriptive prospective study was performed in twenty-five prominent
      mandibular angle patients. All patients were treated surgically to reduce the
      prominent mandibular angle by using a newly designed method. This method is a
      combination of the existing external approach and intraoral approach in order to
      obtain the advantages and to eliminate the disadvantages of each approach.
      Satisfying cosmetic results were attained in all twenty-five patients without any
      serious complications. As such, the new combined technique of external and
      intraoral approach for mandibular angel resection is convenient and useful.

PMID- 11529348
TI  - Life-long food restriction prevents renal membrane lipid deposition and lowers
      renal work in rats.
AB  - Renal cortical brush-border (BBM), basolateral membrane (BLM), and medullary
      plasma membrane (mPM) preparations were analyzed to assess the effects of life
      long food restriction in aged rats on membrane lipid content. Young male Fischer
      344 x Brown-Norway F1 rats consumed food ad libitum (young AL) or were food
      restricted (FR, 60% of AL consumption) for either 6 weeks (young FR) or until the
      age of 30 months old (old FR). Senescent FR rats had 50 per cent decreases in
      fractional excretion of Na and K (p < 0.001) as compared with the young AL rats.
      Long-term FR reduced phosphate and titratable acid excretion by 80 per cent (p <
      0.001). These values were not significantly different from those observed in
      young rats during 6 weeks of FR. Food restriction decreased renal Na, K-ATPase
      activity by 50 per cent (p < 0.001) in both old and young FR animals. Reduction
      of food intake, in old and young rats, decreased all BBM phospholipid
      concentrations (phosphatidylserine, phosphatidylcholine,
      phosphatidylethanolamine, and sphingomyelin) by 50 per cent than in the AL rats
      (p < 0.001). In BLM, chronic FR resulted only in lower phosphatidylcholine
      concentration (by 21%, p < 0.05) while phosphatidylethanolamine was increased
      approximately 80 per cent (p < 0.001). Total phospholipid content in mPM was
      progressively decreased by 23 per cent (p < 0.05) in the young FR group to be 55
      per cent (p < 0.001) in the old FR rats. Cholesterol content was reduced in BBM
      and mPM by 38 per cent and 25 per cent (p < 0.05), respectively, during long-term
      FR. Both total phospholipid and cholesterol contents detected in mPM of the old
      FR rats were significantly lower than those obtained from the young FR animals
      (by 42%, p < 0.001 and 12%, p < 0.05, respectively). Plasma glucose, blood urea
      nitrogen, and body weight maintained at significantly lower levels during chronic
      FR. That life-long FR could prevent renal membrane lipid deposition and could
      lower renal work may explain the mechanisms that FR can delay the onset and
      diminish the severity of age-associated renal diseases.

PMID- 11529349
TI  - Effects of ACE-I on diabetic cardiovascular complications: anti-hypertensive and
      non-antihypertensive doses.
AB  - To evaluate the effects of angiotensin converting enzyme inhibitor (ACE-I) on
      diabetic cardiovascular complications, a streptozotozin (STZ, i.p., 70 mg/kg BW)
      induced diabetes rat model was used. The animals were separated into four major
      groups including: control (NSS), STZ-treated rats, STZ-treated rats received
      daily oral feeding of cilazapril starting one day after STZ injection (STZ-C1),
      and STZ-treated rats received daily oral feeding of cilazapril eight weeks after
      the STZ injection (STZ-C8). Within the groups of STZ-C1 and STZ-C8, the animals
      were also divided into three subgroups of six rats that received different doses
      of cilazapril treatment, 0.01 mg/Kg BW, 1 mg/Kg BW, and 10 mg/Kg BW. By using the
      modified isolated heart model, the parameters of mean arterial pressure (MAP),
      heart rate (HR), left ventricular isotonic contraction (LVIC), aortic flow rate
      (AFR), coronary flow rate (CFR), and ratio of heart weight per body weight (R)
      were assessed for each groups 8 and 20 weeks after the STZ injections. Moreover,
      the changes of wall thickness of the left ventricular wall (LV), right
      ventricular wall (RV), and interventricular septal wall (IVS) were monitored from
      the scanning electron micrographs of each heart. The results indicated that in
      both STZ-C1 and STZ-C8, the diabetic hypertension could be prevented or treated
      by anti-hypertensive doses of cilazaprils. Besides, the values of AFR, CFR, and
      LVIC were significantly increased when comparing between the STZ and STZ-C1 or
      STZ-C8. The results of morphological examinations indicated that: (1) left
      ventricular walls of the three hearts of STZ-rats had increased significantly
      more than controls. (2) Right ventricular walls and interventricular septal walls
      were not significantly different among STZ-rats, cilazapril treated STZ-rats and
      age matched controls. Therefore, it is concluded that ACE-I could act either as a
      cardioprotective or therapeutic agent for diabetic hearts. Both major anti
      hypertension and anti-trophic effects of ACE-I have already been elucidated.

PMID- 11529350
TI  - Energy expenditure and physical activity of obese and non-obese Thai children.
AB  - The objective of this study was to assess the energy expenditure and physical
      activity in obese (n=21) and non-obese (n=21) children (aged 9-12 years) in
      Bangkok. Anthropometric measurements were performed. Energy expenditure and
      physical activity were determined by indirect calorimetry (based on oxygen
      consumption) and the heart rate monitoring method. Physical activity index was
      calculated by the ratio of total energy expenditure (TEE) to sedentary energy
      expenditure (SEE). The results showed that obese children had significantly
      greater (p<0.05) body weight, body mass index, relative weight, body fat (%), fat
      mass except for height, and fat free mass than the non-obese group. The TEE, SEE,
      and activity energy expenditure (AEE) were higher (p<0.05) in the obese children
      when compared with the non-obese ones. The mean values of respiratory quotient
      (RQ) were 0.91+/-0.06 in obese and 0.89+/-0.08 in the non-obese group,
      respectively, indicating the contribution of carbohydrate substrate to energy
      production. Both obese and non-obese children were similar in the physical
      activity index level of 1.48+/-0.17 and 1.51+/-0.22, respectively, which was
      lower than that recommended by the World Health Organization (1.7). In
      conclusion, energy expenditure of obese children was higher than non-obese
      children because of greater body weight. Furthermore, the physical activity of
      both groups was lower than that recommended by WHO. To prevent obesity in
      children, programmimg of exercise and activities as well as nutritional education
      should be emphasized for school children and parents.

PMID- 11529351
TI  - Current management of Helicobacter pylori infection.
AB  - Helicobacter pylori is commonly found throughout the world. It is associated with
      a wide range of gastroduodenal diseases. Knowledge regarding the characteristic
      organism, behaviour, and related clinical conditions is extensive. Indeed, the
      bacteria is not the only factor which can cause the diseases, the host as well as
      environmental factors are also important. Largely, H. pylori is disappearing
      worldwide due to eradication of this organism allowing frequency of an H. pylori
      negative ulcer to relatively increase and may be more difficult to treat. The PPI
      triple therapy remains the first line of treatment with quadruple therapy as the
      second rescue line. The rising of bacterial resistant strains is a new problem
      which requires new drugs to improve the efficacy of the current regimens.

PMID- 11529352
TI  - Diagnostic hysteroscopy at King Chulalongkorn Memorial Hospital: 7 years
      experience.
AB  - We reported our experience and results of diagnostic hysteroscopy performed on
      294 patients between June 1994 and May 2000 at the Gynecologic Endoscopy Unit,
      King Chulalongkorn Memorial Hospital. Diagnostic hysteroscopy was performed
      successfully in 286 patients (97.3%), allowing thorough inspection of the uterine
      cavity. Cervical dilatation was required in 146 patients (49.6%). The most common
      indication was endometrial polyps (34.4%) followed by infertility (19.4%) and
      abnormal uterine bleeding (14.9%), respectively. Each of the hysteroscopic
      findings accounted for 103 patients (35%) in endometrial polyps and normal
      endometrium. The procedure failed in 8 patients (2.71%) due to uterine
      perforation. In conclusion, diagnostic hysteroscopy should be considered as a
      safe, effective and successful investigation procedure for suspected intrauterine
      pathology.

PMID- 11529353
TI  - Pipelle versus fractional curettage for the endometrial sampling in
      postmenopausal women.
AB  - The experimental and cross over design study was performed to compare the pain,
      ability to sample the endometrial issue, and pathological results from pipelle
      and fractional curettage in post menopausal patients. Thirty naturally menopausal
      patients who visited King Chulalongkorn Memorial Hospital with abnormal bleeding
      per vagina from June 1 to December 31, 1997, were enrolled in the study. In group
      A,endometrial tissue sampling was first conducted by Pipelle and followed by
      fractional curettage. In group B, the fractional curettage was performed before
      Pipelle. The results showed that the pain derived by the visual analogue scale of
      Pipelle and fractional curettage were 3.34 +/- 1.44 (mean +/- SD) and 6.58 +/-
      1.75 respectively (p<0.01). The sensitivity and specificity of Pipelle in
      endometrial tissue samplings compared with fractional curettage were 87.5 and 100
      per cent, respectively. One from 3 cases of adeneocarcinoma of the endometrium
      could not be detected by Pipelle. In conclusion, Pipelle significantly produced
      less pain than fractional curettage. Even though Pipelle is a simple and easy
      method for endometrium sampling, the use of Pipelle to replace fractional
      curettage in the management of postmenopausal bleeding should be done with
      caution. False negative could occur in the focal disease of malignancy of the
      endometrium.

PMID- 11529354
TI  - Comparison of the outcome of intracytoplasmic sperm injection using fresh and
      frozen-thawed epididymal spermatozoa obtained by percutaneous epididymal sperm
      aspiration.
AB  - The study was conducted to compare the outcome of intracytoplasmic sperm
      injection (ICSI) between fresh and frozen-thawed epididymal spermatozoa retrieved
      by percutaneous epididymal sperm aspiration (PESA) from obstructive azoospermic
      men. Overall, 53 PESA procedures were performed in 42 obstructive azoospermic
      men, followed by ICSI procedures with either fresh (n = 40) or frozen-thawed (n =
      13) epididymal spermatozoa. Comparing all ICSI cycles with fresh and frozen
      thawed epididymal spermatozoa, the fertilization rates (77.4 vs 86.8%) and the
      cleavage rate (91.3 vs 95.1%) were not statistically different. A total of 64
      embryo transfers were performed: 48 embryo transfers after the use of fresh
      epididymal spermatozoa and 16 embryo transfers after the use of frozen-thawed
      spermatozoa. The overall pregnancy rate per embryo transfer was also similar
      between both groups (40.8 vs 40%). The implantation rate per embryo (18.2 vs
      12.7%), clinical pregnancy per embryo transfer (36.7 vs 33.3%) and
      delivery/ongoing pregnancy rate (36.7 vs 33.3%) were not statistically different.
      In conclusion, there were no significant differences of the outcome of
      intracytoplasmic sperm injection using fresh and frozen-thawed epididymal
      spermatozoa obtained by PESA.

PMID- 11529356
TI  - Fetal transverse cerebellar diameter in Thai population.
AB  - We developed a nomogram for transverse cerebellar diameter (TCD) in Thai fetuses
      by recruitment of 153 normal pregnant women in the first trimester. The
      gestational age calculated by the certain last menstrual period and the first
      trimester ultrasound were in agreement. The pregnant women were stratified into 4
      groups and scanned at four weekly intervals: group A was first scanned at 14
      weeks, group B at 15 weeks, group C at 16 weeks, and group D at 17 weeks. A total
      of 699 measurements from 14 to 40 weeks of gestation were obtained. The data were
      analyzed for mean and standard deviation; and the best fit mathematical model was
      derived. The TCD grew progressively along gestational age. The growth rate was
      slightly less than that of a Western study after 28 weeks of gestation. This
      could serve as the basis for gestational dating in fetuses with aberrant fetal
      growth.

PMID- 11529355
TI  - Short course zidovudine maternal treatment in HIV-1 vertical transmission:
      randomized controlled multicenter trial.
AB  - A multicenter randomized, double blind, placebo-controlled clinical trial was
      conducted to evaluate the effectiveness of a short course of oral zidovudine
      (ZDV) treatment in HIV-1 infected pregnant women, starting at 38 weeks of
      gestation plus ZDV infusion during labor until delivery, to reduce HIV-1 vertical
      transmission in non-breast fed infants. One hundred and eighty two asymptomatic
      antiretroviral naive HIV-1 infected pregnant women were enrolled. Each patient
      was randomly allocated into either the ZDV or placebo group. The ZDV group
      received 250 mg ZDV orally twice a day initiated at 38 weeks' gestation until the
      onset of labor. During the intrapartum period, ZDV infusion at the rate of 2
      mg/kg was administered within the first hour and then continuously infused at the
      rate of 1 mg/kg/h until delivery. The placebo group received an identical capsule
      during pregnancy and normal saline infusion during labor until delivery. HIV-1
      transmission was documented by nested polymerase chain reaction in infants at
      birth and at 1, 3 and, 6 months of age. The estimated HIV-1 vertical transmission
      rate was 14.9 per cent (95% CI = 11.1 to 18.7) and 16.3 per cent (95% CI = 12.3
      to 20.9) in ZDV and placebo group, respectively (p > 0.05). The short course ZDV
      in antiretroviral naive pregnant women initiated at 38 weeks' gestation plus
      intrapartum ZDV infusion without treatment in the infants was not effective to
      prevent HIV-1 vertical transmission.

PMID- 11529357
TI  - Serum human chorionic gonadotropin regression pattern in persistent trophoblastic
      disease during chemotherapy.
AB  - The objective of this study was to identify the regression pattern of serum beta
      hCG in persistent trophoblastic disease patients after initiating chemotherapy.
      Eighty-nine women who were diagnosed as persistent trophoblastic disease in King
      Chulalongkorn Memorial Hospital between January 1985 and December 1998, and
      received single agent chemotherapy were included. The incidence was 20.2 per cent
      of total gestational trophoblastic disease patients. Seventy-two (80.9%) from 89
      patients were recruited in our study. Sixty-four (88.9%) patients responded to
      first-line chemotherapy and 8 patients (11.1%) resisted. Suction curettage was
      done as initial treatment in 61 (84.7%) cases. Most of them (95.8%) received
      actinomycin-D as first line treatment. Total courses of chemotherapy averaged 4
      courses, but increased to 8.5 courses in the resistant group. Mean time of serum
      beta-hCG to remission was 16.7 and 21.5 weeks in the chemo-sensitive and chemo
      resistant group, respectively. Average time to start chemotherapy was in the
      tenth week, and in the resistant group it was started in the sixth week.
      Chemotherapy regimen was changed in the fifteenth week. Initial serum beta-hCG
      levels were not significantly different between the two groups. The reduction
      rates of beta-hCG were significantly different from the third to the seventh week
      in the chemo-sensitive and chemo-resistant groups, which was during the second
      and third course of chemotherapy (P<0.05). In conclusion, by using the reduction
      rate, the regression pattern of serum beta-hCG level in persistent trophoblastic
      disease patients was significantly different between the chemosensitive and
      chemoresistant group from the third to the seventh week after starting
      chemotherapy.

PMID- 11529358
TI  - The role of maternal serum C-reactive protein and white blood cell count in the
      prediction of chorioamnionitis in women with premature rupture of membranes.
AB  - This study was performed to evaluate the diagnostic performance of maternal serum
      C-reactive protein, maternal white blood cell (WBC), and neutrophil counts in the
      detection of histologic chorioamnionitis. One hundred and twenty six pregnant
      women after at least 28 weeks of gestation with premature rupture of membranes
      (PROM) were studied. Blood samples for C-reactive protein, WBC and neutrophil
      counts were taken at delivery. Placental histology was evaluated for histologic
      chorioamnionitis. Maternal and neonatal complications were observed. Among women
      with and without histologic chorioamnionitis, the maternal WBC and neutrophil
      counts were different (P<0.05) but the maternal serum C-reactive protein was not.
      Cutoff values for C-reactive protein, WBC, and neutrophil counts were 0.5 mg/dL,
      15,000 cell/mm3, and 80 per cent, respectively. Sensitivity and specificity were
      56 per cent and 58 per cent for C-reactive protein, 60 per cent and 63 per cent
      for WBC count, and 62 per cent and 54 per cent for neutrophil count,
      respectively. In conclusion, the maternal serum C-reactive protein, WBC, and
      neutrophil counts have poor diagnostic performance for histologic
      chorioamnionitis.

PMID- 11529359
TI  - Correlation between human follicular diameter and oocyte recovery, metaphase II
      oocytes and fertilization rate in intracytoplasmic sperm injection programs.
AB  - This prospective study was undertaken to establish the correlation between the
      follicular diameter, oocyte recovery, metaphase II (MII) oocyte, and
      fertilization rate in intracytoplasmic sperm injection (ICSI) programs. Thirty
      one patients undergoing 31 ICSI cycles from August 1998 to January 1999 at King
      Chulalongkorn Memorial Hospital were studied. The patients were stimulated with
      either short or long GnRHa portocol. During transvaginal aspiration of follicles,
      follicular diameters were measured. The maturation stage of oocytes and
      fertilization rate were evaluated. Four hundred and seventy eight follicles were
      measured and classified into 3 groups, group A (<10 mm), group B (10-14 mm) and
      group C (>14 mm). The oocyte recovery rate and MII oocytes were different between
      groups A, B, and C but the fertilization rate was not different. In conclusion,
      the follicular diameter correlated with oocyte recovery and oocyte maturation but
      not with the fertilization rate in ICSI programs. The quality of embryos was
      lower in oocytes from small follicles.

PMID- 11529360
TI  - Effects of contaminated endometriotic contents on quality of oocytes.
AB  - The mechanism of infertility associated with endometriosis is poorly understood.
      There is evidence supporting that women with ovarian endometriosis have a lower
      pregnancy rate than women with peritoneal lesions only. This study aimed to
      evaluate the effects of endometriotic contents contamination while retrieving
      oocytes on oocytes' quality. Thirty-eight infertile patients with endometriotic
      cysts from January 1993 to June 2000 were enrolled in this study. There were no
      statistically significant differences among the quality of oocytes and embryos
      from the contaminated, non-contaminated, and control group. However, the
      fertilization rate and pregnancy rate were impaired by the contamination of
      endometriotic contents. We conclude that ovarian endometriosis should be treated
      before starting in vitro fertilization program in order to increase the pregnancy
      outcome.

PMID- 11529361
TI  - Clinical study of a monophasic pill containing 20 microg ethinylestradiol and 150
      microg desogestrel in Thai women.
AB  - OBJECTIVES: To evaluate the contraceptive reliability and clinical effects of a
      monophasic oral contraceptive containing 20 microg ethinylestradiol and 150
      microg desogestrel (Mercilon) in Thai women. METHOD: The study was carried out at
      the Family Planning Clinic of King Chulalongkorn Memorial Hospital, Bangkok,
      Thailand. One hundred and forty six healthy women of fertile age were enrolled
      and treated with the study oral contraceptives for 12 cycles. Clinical data of
      vaginal bleeding, side effects, blood pressure and body weight were assessed
      periodically. RESULTS: One thousand four hundred and twenty five cycles were
      evaluated. No conception occurred. The cycles were almost regular. The incidence
      of irregular bleeding was highest in the first cycle, after the third cycle, the
      value was below 4 per cent. Side effects were very few. There was no change in
      blood pressure. A slight decrease in mean body weight was observed. CONCLUSION:
      The oral contraceptive containing 20 microg ethinylestradiol and 150 microg
      desogestrel has high contraceptive efficacy, good cycle control and minimal side
      effects.

PMID- 11529362
TI  - Pain-relieving effect of local steroid injection in uvulopalatopharyngoplasty.
AB  - An analytical prospective study was performed to determine the post-operative
      pain-relieving effect of local steroid suspension injection in
      uvulopalatopharyngoplasty. From February 2000 to October 2000, 48 adult patients
      from 20 to 67 years of age, were scheduled to receive uvulopalatopharyngoplasty.
      Triamcinolone acetonide (Kenacort A) was injected onto the raw surface of the
      left-sided tonsillar fossa and left-sided soft palate after tonsillectomy and
      uvulopalatopharyngoplasty. Other preoperative and post-operative medications
      including antibiotics, anesthesia and surgical techniques were standardized.
      Visual analog scales were used to assess the level of pain sensation on the left
      and right side of the throat daily from day 0 (Operative day) to post-operative
      day 10. A paired t-test showed significant differences in post-operative pain
      level between the study side (left) and the control side (right) at day 2, day 4,
      and in the overall analysis (p < 0.05).

PMID- 11529363
TI  - Atrial flutter in fetuses and early childhood: a report of eight cases.
AB  - Atrial flutter is an uncommon arrhythmia in children. The presenting features and
      treatment responses of two fetuses and six children with atrial flutter were
      presented. Two patients were diagnosed prenatally at 31 and 35 weeks' gestation.
      One patient was successfully controlled in utero by maternal administration of
      digoxin and the other by direct current cardioversion after delivery. Two fetuses
      and 2 of 6 children had normal cardiac structure by echocardiogram. Three
      patients had right atrial enlargement due to atrial primun septal defect,
      secundum atrial septal defect with primary pulmonary hypertension, and
      endomyocardial fibrosis. One patient developed atrial flutter with sinus node
      dysfunction after surgical correction of total anomalous pulmonary venous
      connection. Four cases presented as atrial flutter with regular atrioventricular
      conduction (2:1 or 3:1 conduction) while the remainder presented with irregular
      atrioventricular conduction. Heart failure was presented in two patients and
      improved after the arrhythmias were controlled. Successful termination of atrial
      flutter was accomplished by using DC cardioversion in 4 patients and one patient
      converted to normal sinus rhythm following combination of digoxin and amiodarone
      administration. Digoxin was administered for one year as the prophylactic
      medication in six patients. None had recurrence of atrial flutter during the
      follow-up period of one to four years. Two patients required chronic digoxin and
      amiodarone therapy. We concluded that atrial flutter in fetuses and early
      childhood carries a good prognosis. Acute treatment with direct current
      cardioversion is sufficient in most patients, combination of digoxin and
      amiodarone may be an alternative therapy to convert atrial flutter.

PMID- 11529364
TI  - Tonsillar fossa steroid injection for reduction of the post-tonsillectomy pain.
AB  - Fifty patients (26 males and 24 females) who underwent tonsillectomy were then
      treated with injection of the long acting steroid (Kenacort-A) into the right
      tonsillar fossa after the operation. The left side was used as the control. Post
      operative pain was assesed by the patients and was graded and recorded daily as
      mild, moderate, and severe pain on both sides of the throat for 2 weeks. A
      significant reduction of pain in the tested side (right side) was noted in the
      majority of the patients. The duration of pain was shorter in the right side than
      the left side. It seemed to significantly reduce the post-tonsillectomy pain.
      Because of its simplicity, cost effectiveness, and no complications, the
      technique should be used for pain-free tonsillectomy in non-contraindicated
      cases.

PMID- 11529365
TI  - Allograft replacement in limb salvage surgery for bone tumors.
AB  - A retrospective study of a series of eleven patients with active, aggressive
      benign and malignant bone tumors who were treated by radical resection and
      massive match-sized allograft replacement was reviewed. There were seven giant
      cell tumors and four osteosarcoma cases involving mainly either the lower end of
      the femur or upper end of the tibia. The age of the patients ranged from 11 to 50
      years. As the follow-up period was rather short, ranging from 9 to 60 months, the
      patients are all still alive. Complications included two infections, one local
      recurrence, and two with resorption of the articular surface of the
      osteoarticular graft. Though psychosocial benefit was gained in patients with
      this limb salvage procedure, functional evaluation did not yield a satisfactory
      result.

PMID- 11529366
TI  - Surgical epicondylar axis vs anatomical epicondylar axis for rotational alignment
      of the femoral component in total knee arthroplasty.
AB  - The anatomical epicondylar (AEpi) axis and the surgical epicondylar (SEpi) axis
      have been widely used as the epicondylar axis, one of the most commonly used axes
      for rotational alignment of the femoral component in total knee arthroplasty. The
      purpose of this study was to evaluate the differences and reliability between
      these two axes. Computerized tomography scan of the distal femur was done in 55
      osteoarthritic knees. Thirty-two knees were varus and 23 knees were neutral in
      alignment. Axes for rotational alignment of the femoral component were lined
      including posterior condylar (PC), anteroposterior (AP), AEpi, and SEpi axes.
      Angles between each pair of axes were measured including PC-AEpi, PC-SEpi, AP
      AEpi, AP-SEpi and AP-PC. The average PC-AEpi angle was 5.7 degrees +/- 1.7
      degrees. The average PC-SEpi angle was 1.5 degrees +/- 2.1 degrees. The average
      AP-AEpi angle was 90.2 degrees +/- 1.0 degrees. The average AP-SEpi angle was
      94.5 degrees +/- 1.3 degrees and the average AP-PC angle was 95.9 degrees +/- 2.0
      degrees. Twenty-nine per cent of knees had prominent medial epicondyle (a
      landmark for AEpi axis) and 5 per cent had prominent medial sulcus (a landmark
      for SEpi axis). The lateral epicondyle was prominent in all knees. There were no
      significant differences of all angles of referencing axes between men and women
      (p>0.05). There were no significant differences between varus and neutral knees
      in terms of PC-AEpi angle and PC-SEpi angle (p>0.05). The AEpi axis was more
      perpendicular to the AP axis and more external rotated to the PC axis than the
      SEpi axis. Because the perpendicular line to the AEpi axis was closer to the AP
      axis than that of the SEpi axis and the AEpi axis provided appropriate external
      rotated to the PC axis, the AEpi axis was more reliable for rotational alignment
      of the femoral component than the SEpi axis. On the other hand, SEpi axis,
      providing less external rotated to the PC axis, may be difficult to define and
      could cause patellofemoral tracking problems in total knee arthroplasty.

PMID- 11529367
TI  - The biomechanical study of atlantoaxial fixation.
AB  - Recent studies of various C(1-2) constructs have confirmed superior stability
      with transarticular screw fixation. In the meantime, our study on the C2
      morphology in Thai people found about 4 per cent of the pedicles were too small
      for the 3.5 mm. C(1-2) transarticular screw. In order to select a smaller screw
      to use in this operation, we performed a biomechanical testing of 2 sizes of
      screw (2.7 mm, 3.5 mm) for transarticular screw fixation and Gallie's wiring,
      comparison in terms of stiffness in flexion, extension, torsion, anterior and
      posterior shear loads. There were no statistical differences of the stiffness
      between 2.7 mm and 3.5 mm transarticular screw fixation in all directions,
      whereas there were significantly greater stiffness of transarticular screw over
      Gallie's wiring in various directions (P<0.05).

PMID- 11529368
TI  - Plate-screw-wiring technique for the treatment of periprosthetic fracture around
      the hip: a biomechanical study.
AB  - Biomechanic properties, bending stiffness and torsional strength, were determined
      in three different fixation techniques including lateral plating, lateral plating
      with cerclage wires, and 90 degrees-90 degrees anterior and lateral plating
      employed in treatment of the femoral shaft fracture with the presence of a
      femoral prosthesis. Five pairs of human femora with a man made cemented
      periprosthetic Johansson et al fracture classification type II were used in the
      experiments. The study showed that 90 degrees-90 degrees anterior and lateral
      plating produced the best increment in both biomechanic properties. In clinical
      practice, most of the soft tissue around femoral bone had to be dissected to do
      this technique, which would affect bone healing. Further study regarding the
      other properties, benefits, and disadvantages of these three techniques should be
      conducted before selecting the best method for treatment of the patients.

PMID- 11529369
TI  - The open reduction and internal fixation of humeral diaphysis fracture treatment
      with a medial approach.
AB  - From 1995 to 2000, twenty-three patients with fracture of the humeral shaft were
      treated by medial approach and internal fixation using AO/ASIF plate and screws.
      Follow-up was possible for 21 fractures. There were 16 male and 5 females. The
      ages ranged from 16 to 55 years (mean, 29 years). The average period of follow-up
      was 4.5 months (range, 3-12 months). There was no evidence of implant failure and
      nonunion during follow-up. The average lack of complete extension of the elbow
      was five degrees. There was one case of transient radial nerve palsy. As such,
      the medial approach to humeral shaft and internal fixation with plate and screws
      for humeral diaphysis fracture was determined to be a viable technique.

PMID- 11529370
TI  - Thrombolytic treatment for acute ischemic stroke: a 2 year-experience at King
      Chulalongkorn Memorial Hospital.
AB  - We studied 9 stroke patients who received a thrombolytic agent at King
      Chulalongkorn Memorial Hospital. Six presented with stroke in the middle cerebral
      artery territory and three had basilar stroke. Seven patients were given
      intravenous thrombolysis and 2 received intra-arterial treatment. We strictly
      followed the inclusion and exclusion criteria for intravenous tissue plasminogen
      activator (rt-PA) according to the National Institute of Neurological Disorders
      and Stroke (NINDS) rt-PA study. For patients receiving intraarterial
      thrombolysis, emergency angiograms were performed. Two patients with severe
      basilar stroke dramatically improved after intravenous thrombolysis and had very
      good outcome. Four patients with middle cerebral artery stroke became worse
      within 24 hours. Three of them died in the acute phase due to intracerebral
      hemorrhage (2 cases) and massive infarction with brain herniation (1 case). For
      intra-arterial treatment, good recanalization was seen but clinical improvement
      was insignificant. The result of thrombolytic treatment in this study was not so
      impressive, partly because we only treated the very severe cases. The efficacy of
      this treatment among our population needs to be further investigated.

PMID- 11529371
TI  - Initial outcomes of coronary angioplasty in diabetic patients.
AB  - Diabetes is one of the controllable risk factors of coronary artery disease. Many
      reports have shown that diabetes is a poor prognostic indicator for coronary
      events and revascularization among patients who undergo PTCA or coronary artery
      bypass surgery. The present work, the first prospective study in Thailand, was
      conducted to compare the demographic data and initial outcomes of diabetic
      patients (DM) with those of non-diabetic ones (non-DM) who underwent percutaneous
      coronary angioplasty (PTCA). Data between January 1993 and December 1998 were
      prospectively collected after each procedure and before discharge. During the 6
      year period, 812 patients (DM-280, non-DM-532) were enrolled. The DM group had
      significantly more female patients (45.4 vs 21.1%, p < 0.0001), older age (62.5
      +/- 8.2 vs 60.5 +/- 10.8 y, p < 0.007), less smoking (21.8 vs 43.2%, p < 0.0001),
      more dyslipidemia (56.8 vs 41.9%, p < 0.0001) and a higher incidence of
      hypertension (51.8 vs 42.5%, p = 0.01). The left ventricular ejection fraction,
      indication for PTCA, size of attempted vessel, and number of diseased vessels
      were similar in both groups. The case success rate was 93.9 per cent in the DM
      group and 92.3 per cent in the non-DM group (P=NS). Two patients (0.7%) in the DM
      and three cases (0.6%) in the non-DM group died during hospitalization. Overall
      major adverse cardiac events were not different between both groups (1.4 vs 1.9%,
      P =NS). In conclusion, there were some demographic differences in DM compared
      with non-DM patients who undergo PTCA; but initial outcomes, major adverse
      cardiac events, and mortality rates were not significantly different.

PMID- 11529372
TI  - Pattern of inheritance in three sudden unexplained death syndrome ("Lai-tai")
      families.
AB  - Sudden Unexplained Death Syndrome (SUDS) (or Lai-tai) is sudden death in
      previously healthy young adults without any structural cause of death from
      autopsy findings. Our previous data showed that familial SUDS is not X-linked
      recessive. The objective of this study was to determine the pattern of
      inheritance in familial SUDS using the ECG markers of Brugada syndrome (RBBB and
      ST-segment elevation in V1 to V3), SUDS and presumptive SUDS as phenotypes. We
      employed the standard 12-lead ECG and higher intercostal space (ICS) V1 to V3 (
      V1 to -V3 and -2V1 to -2V3) leads ECG in SUDS relatives after procainamide and
      drew the pedigree. We studied 62 relatives of 9 SUDS victims who died in
      Singapore and selected 3 families (n = 34) for the procainamide test and ECG. The
      mean age was 36.4 +/- 23.6 years (4-78 years). Three SUDS families showed the
      same pattern of inheritance of autosomal dominant.

PMID- 11529373
TI  - Endoscopic management of cholangiocarcinoma.
AB  - Cholangiocarcinoma constitutes the second most common primary liver cancer after
      hepatocellular carcinoma. It is particularly prevalent in regions where liver
      flukes are hyperendemic. Obstructive jaundice is the most common presentation. To
      evaluate patients suspected for cholangiocarcinoma, endoscopy is becoming more
      popular. Endoscopy can provide important information especially cholangiogram and
      tissue diagnosis. Recently, the role of endoscopy has not only been used for
      diagnosis but also for treatment. In this article, the roles of endoscopy for
      diagnosis, therapy, and future modality of treatment for cholangiocarcinoma are
      provided.

PMID- 11529374
TI  - Papillary stenosis in King Chulalongkorn Memorial Hospital: endoscopic findings,
      treatments and result.
AB  - Papillary stenosis usually presents with biliary type abdominal pain,
      significantly elevated liver enzymes, and cholangiogram revealing dilated common
      bile duct without stone. In the Western world, endoscopic biliary sphincterotomy
      is accepted as a standard treatment for papillary stenosis. In Asia, there are
      only a few reports regarding papillary stenosis. This is a report of our
      experience on endoscopic biliary sphincterotomy for papillary stenosis in Thai
      patients. From our ERCP database, twenty-five patients presented with biliary
      type abdominal pain, elevated liver enzymes and dilated common bile duct by
      ultrasonography. All of them underwent ERCP for a diagnosis of possible biliary
      obstruction. Of these 25 cases, seven patients with papillary stenosis were
      identified. All underwent endoscopic biliary sphincterotomy with or without
      biliary dilation and stent placement. These patients were followed for clinical
      improvement and normalization of liver enzymes. Endoscopic biliary sphincterotomy
      was successful in all patients. One patient required additional biliary dilation
      and stent placement. All seven patients reported significant improvement of
      biliary type abdominal pain. Liver enzymes also normalized 3 months after
      endoscopic treatment. There were no severe complications except one patient who
      developed post ERCP pancreatitis while another developed minimal bleeding at the
      sphincterotomy site. Endoscopic biliary sphincterotomy is effective and safe in
      patients with papillary stenosis. Results of our series are comparable to
      previous reports from Western countries.

PMID- 11529375
TI  - Transepidermal water loss during conventional phototherapy in nonhemolytic
      hyperbilirubinemia term infants.
AB  - The evaporation rate from the skin was measured in 40 healthy term infants and 40
      non-hemolytic jaundice term infants who required phototherapy. All infants were
      born at the gestational age of 38-41 weeks. The method for measurement of
      evaporation rate was based on determination of the water pressure gradient close
      to the skin surface. Conventional phototherapy was given in open cribs. In the
      phototherapy group, non of the infants had received phototherapy before the start
      of measurement. Evaporation rate was measured at the chest, interscapular and
      buttock. The measurement was made before phototherapy, 30 minutes, and 6 hours
      after starting phototherapy. The mean evaporation rate increased from 7.2 to 7.8
      and 8.4 g/m2 h, respectively (p<0.001). In the control group, the measurement was
      made at the consecutive time as in the phototherapy group. The mean of the
      evaporate rate was 7.3, 7.6 and 7.5 g/m2 h (p=0.30). We conclude that
      conventional phototherapy in full term infants in open cribs increases
      transepidermal water loss.

PMID- 11529376
TI  - The combined treatment of interferon alpha-2a and thymosin alpha 1 for chronic
      hepatitis C: the 48 weeks end of treatment results.
AB  - The efficacy and safety of IFN alpha 2a and Thymosin alpha1 combination therapy
      in patients with chronic hepatitis C were determined. Twelve chronic hepatitis C
      patients (9 M, 3F), with positive HCV-RNA and histology compatible with chronic
      hepatitis C were included in this open, prospective study. Each patient received
      a combination therapy of IFN alpha 2a 3 mU s.c. TIW and Thymosin alpha1 1.6 mg
      s.c. twice a week for 52 weeks. Up to the present, 11 patients are still being
      followed-up after the end of 52 weeks' treatment. One patient dropped out after
      32 weeks of follow-up due to noncompliance. Responses to treatment were evaluated
      by measuring serum HCV-RNA levels determined by RT-PCR. and serum amino
      transferases at the end of 48 weeks of treatment (end of treatment response:
      ETR). There were 8 naive and 4 previously IFN treated patients with partial
      response with a mean age of 45.0 +/- 10.1 (mean +/- SD). The mean duration from
      diagnosis until treatment was 25.1 +/- 22.9 months. The mean AST, ALT, and HCV
      RNA levels before treatment were 79.5 +/- 36.8 U/L, 128.3 +/- 68.5 U/L, and
      3.9+1.9 x 10(5) copies/ml respectively. Serum AST, ALT, and HCV-RNA levels were
      significantly lower at week 24 and 48 after treatment compared to before
      treatment (p<0.05). Of 11 cases, complete HCV-RNA clearance at week 24 was noted
      in 33.3 per cent, whereas, normal alanine aminotransferase values (ALT < 40 U/L)
      were observed in 41.7 per cent of patients. Complete HCV-RNA clearance and normal
      alanine aminotransferase at week 48 were seen in 45.5 per cent of the patients.
      At the end of week 48, complete response occurred in 4 of 5 naive patients. Minor
      side effects were observed during treatment with this combination therapy and
      these included myalgia (33.3%), mild form of alopecia (33.3%), and weight loss
      (8.3%). In patients with chronic hepatitis C, Interferon alpha 2a and Thymosin
      alpha1 combination therapy produced a good response rate especially in naive
      patients with acceptable safety profile. The sustained response will be
      determined after the completion of follow-up for another 6 months.

PMID- 11529377
TI  - Necrotizing ileitis caused by cytomegalovirus in patient with systemic lupus
      erythematosus: case report.
AB  - We report a systemic lupus erythematosus (SLE) patient with necrotizing ileitis
      diagnosed at a tertially care centre in Thailand. The patient was surgically
      explored because peritonitis was suspected and segmental gangrenous and
      perforation of the terminal iliem were found. The pathological finding was
      necrotizing ileitis with appearance of cytomegalic intranuclear inclusion body.
      The presence of cytomegalovirus (CMV) infection in tissue was confirmed by CMV
      DNA detection using polymerase chain reaction and ELISA probe hybridization
      method. The hemoculture and peritoneal fluid culture results revealed no
      pathogenic organisms. Postoperatively, the clinical course of the patient
      deteriorated and she developed hypotension. Vasopressive drugs were administered
      without clinical improvement. She expired on day 5 postoperation. Regarding CMV
      infection, the organism involves the small bowel in only 4.3 per cent of all CMV
      infections of the gastrointestinal tract. Isolated cases of ileal perforation due
      to CMV infection have never been reported in a SLE patient. Thus, chronic right
      lower abdominal pain, fever with or without diarrhea in immunocompromised
      patients should cause clinicians to consider CMV ileitis in the differential
      diagnosis. Immediate surgical resection and prompt antiviral therapy lead to
      successful treatment.

PMID- 11529378
TI  - Eradication rates of Helicobacter pylori between metronidazole-sensitive and
      metronidazole-resistant strains with metronidazole containing regimen in Thai
      patients with peptic ulcer disease.
AB  - The results of the in vitro metronidazole resistance on Helicobacter pylori (H.
      pylori) eradication have been inconclusive. Metronidazole resistance varies among
      different geographical locations and a previous study from Thailand reported an
      in vitro metronidazole resistance of H. pylori of 51 per cent. This study was
      designed to investigate further the effect of the in vitro metronidazole
      resistance on the outcome of eradication of H. pylori in the Thai population.
      Fifty two patients with active gastric ulcer (GU) and duodenal ulcer (DU) who had
      positive culture for H. pylori were studied. All of these patients had positive
      rapid urease test (CLO test, Delta West, Australia) using gastric biopsy
      specimens from the antrum and body taken at the time of initial upper endoscopy.
      In vitro antimicrobial susceptibility test was performed using Epsilometer test
      (AB Biodisk, Solna, Sweden). All patients received a one-week triple regimen
      consisting of omeprazole 20 mg twice daily, clarithromycin 500 mg twice daily,
      metronidazole 500 mg twice daily. Patients with GU continued with another five
      weeks of omeprazole 20 mg twice daily and patients with DU received another three
      weeks of omeprazole 20 mg twice daily. Upper endoscopy was repeated at four weeks
      after the end of the treatment. Three antral and two body biopsy specimens were
      obtained for identification of H. pylori using CLO test, histology (modified
      Giemsa stain) and culture. All of these tests had to be negative to confirm a
      successful eradication. Metronidazole-resistant (MR) strains with MIC > or = 32
      mg/l were identified in 27 of the 52 patients (51.92%), whereas, metronidazole
      susceptible (MS) strains were isolated from 25 patients (48.08%). Five patients
      were lost to follow-up and one patient had drug allergy. Successful eradication
      as defined by negative CLO test, histology and culture was attained in 17/23
      (73.91%) patients (GU = 6, DU = 16, GU and DU = 1) with MR strains. 20 out of 23
      (86.96%) patients (GU = 9, DU = 12 GU and DU = 2) who had MS strains. The
      difference was not statistically significant in both groups (P > 0.05). The ulcer
      healing was, however, highly achieved in both groups (MS = 95.65%, MR = 91.30%, P
      > 0.05). In vitro metronidazole resistance was high in this population group
      although this does not predict the outcome of eradication in patients with GU and
      DU.

PMID- 11529379
TI  - Malignant duodenal stromal tumor: the first case report in Thailand and review of
      the literature.
AB  - The authors presented a middle aged Thai patient with malignant duodenal stromal
      tumor identified at a tertially care centre in Thailand. The patient presented
      with obscure gastrointestinal bleeding and the small bowel endoscopy revealed a
      bleeding tumor mass at the fouth part of the duodenum. The patient underwent
      segmental duodenectomy with end to end anstosomis. The histopathology of the
      tumor composed of interlacing bundles of spindle cells with oval to elongated
      pleomorphic nuclei and eosinophilic cytoplasm. The immunohistochemistrical study
      confirmed the diagnosis of malignant stromal tumor with smooth muscle
      differentiation. The computer tomography scan (CT scan) of the abdomen showed no
      evidence of metastasis. Postoperatively, the patient's clinical condition showed
      continuous improvement without further gastrointestinal bleeding. The patient has
      remained healthy up to present (six months of follow-up). A high level of
      suspicion to detect this malignant tumor especially in a patient presenting with
      obscure gastrointestinal bleeding and effective surgical treatment allow better
      clinical outcome in this rare and fatal malignancy.

PMID- 11529380
TI  - Does GnRH analog improve the final height in Thai girls with idiopathic central
      precocious puberty?
AB  - Ten Thai girls with idiopathic central precocious puberty (ICPP) were treated
      with gonadotrophin releasing hormone (GnRH) analog for a mean period of 1.5+/-0.4
      years. The predicted adult height at the end of treatment was significantly
      higher than that at the start of treatment (158.2+/-7.9 vs 153.0+/-8.7 cm,
      p=0.009). In addition, treatment with GnRH analog could significantly regress the
      breast staging from 3.4+/-0.8 to 2.6+/-1.0 (p=0.04),but not the pubic hair
      staging. Five of them reached a final height which was not significantly higher
      than the predicted adult height before treatment (153.1+/-4.8 vs 150.7+/-1.0 cm,
      p=0.5). In conclusion, treatment with GnRH analog in Thai girls with ICPP can
      improve the predicted adult height and regress the breast staging. However, the
      improvement of final height is not promising.

PMID- 11529381
TI  - Rett syndrome in Thai female girls: clinical studies.
AB  - Rett syndrome consists of a highly complex but consistent set of clinical signs
      and symptoms. Clinical characteristics consist of microcephaly, delayed
      psychomotor development, autistic behavior, stereotyped hand-washing, and
      seizures. Over a period of 14 years (1987-2000), 7 patients with Rett syndrome
      were evaluated at the Out Patient Unit, King Chulalongkorn Memorial Hospital,
      Bangkok, Thailand. All seven patients were females aging 1 1/2 to 5 years old
      when diagnosis was established. All were appearently normal at birth and had
      developmental regression after a period of time. All of them developed
      microcephaly, autistic features, seizures, and stereotyped hand-washing-movement.
      Five of seven patients (71.42%) developed episodic hyperventilation. All cases
      had abnormal electroencephalogram. Computer tomography scan were examined in 3
      cases which were normal while magnetic resonance imaging were studied in 2 cases
      and was abnormal in one.

PMID- 11529382
TI  - Oral ceftibuten switch therapy for acute pyelonephritis in children.
AB  - The available oral third generation of cephalosporin, "ceftibuten" was used to
      substitute the intravenous drug after defervescence in acute pyelonephritis in
      children. This randomized controlled study compared the efficacy of an oral
      ceftibuten switch therapy with a ceftriaxone in both short-term and long-term
      outcomes. 36 99mTc-dimercaptosuccinic acid (DMSA) scan proved pyelonephritis
      patients were randomized into the study group, "ceftibuten" (N=18) and the
      control group, "ceftriaxone" (N=18). Ceftriaxone (75 mg/kg/day) was the initial
      antibiotic in both groups. After defervescence for 24-48 hours, oral ceftibuten
      (9 mg/kg/day) was substituted in the study group and continued for 10 days. The
      subject characteristics and laboratory data were not different between the two
      groups. The urine culture at D14 was sterilized in both groups. The incidence of
      renal scarring was 66.6 per cent and 61.1 per cent in the study group and the
      control group respectively. The rate of recurrent infection showed no statistical
      significance. The duration of hospitalization was shorter in the study group than
      in the control. In conclusion, oral ceftibuten switch therapy can be recommended
      as a safe and effective treatment for acute pyelonephritis in children. The use
      of oral therapy may result in a significant reduction of health care expenditure.

PMID- 11529383
TI  - PRISM score and factors predicting mortality of patients with respiratory failure
      in the pediatric intensive care unit.
AB  - A total of 96 patients with respiratory failure who required mechanical
      ventilation admitted to the PICU, Chulalongkorn Hospital from July 1998 to June
      1999 were reviewed to evaluate the PRISM score for mortality prediction and to
      identify factors that might influence the outcome. The statistical difference in
      outcome between the 2 groups (survivors and non-survivors) were underlying
      diseases, age, maximum positive inspiratory pressure (PIP), maximum positive end
      expiratory pressure (PEEP), maximum fractional inspiratory oxygen (FiO2) and
      PRISM score (p < 0.05). However, based on the original logistic regression
      equation, the predicted mortality from PRISM score in our study was much lower
      than our actual mortality (2.4% vs 26.0%). The sensitivity and specificity of
      mortality predicted by PRISM score calculated at cut-off r = 0.0 (expected
      mortality = 50%) was 4 per cent and 97 per cent respectively. In conclusion, the
      original PRISM score underpredicted the mortality outcome in our patients with
      respiratory failure. This suggests that PRISM score is population dependent and
      should be modified before being used with our patients.

PMID- 11529384
TI  - Growth and development of children conceived by intracytoplasmic sperm injection
      at King Chulalongkorn Memorial Hospital.
AB  - A number of concerns have been raised about children conceived by
      intracytoplasmic sperm injection (ICSI). In this study, 75 babies in the King
      Chulalongkorn Memorial Hospital ICSI programme were determined during pediatric
      follow-up to assess the growth, development and congenital malformations from
      April 1997 to December 2000. Male to female ratio was 1:1.27. Mean birth weight
      for singletons was not different from the general population. Thirty six per cent
      of the babies weighed less than 2,500 g, which was almost four times higher than
      naturally conceived babies. Approximately 27 per cent of deliveries were multiple
      pregnancies compared to 0.93 per cent from natural conception. Prematurity rate
      was 25 per cent and 85.7 per cent of deliveries were carried out by caesarian
      section. One baby (1.3%) had major congenital malformation and 37 babies (49.3%)
      had one or more minor defects. Most of the babies had weight, height, and head
      circumference within normal ranges. After correction for gestational age, all the
      premature babies caught up growth within the first year of life. Eleven babies
      (14.7%) had abnormal or questionable results or Denver II at different ages.
      Longer-term follow-up is necessary to properly assess the growth and
      developmental outcome of the ICSI babies.

PMID- 11529385
TI  - Childhood cryptococcosis: an increasing problem in the era of AIDS.
AB  - The authors reported 8 children with cryptococcosis from King Chulalongkorn
      Memorial Hospital from 1991 to 2000. Five patients were older than five years.
      The two common underlying diseases were HIV/AIDS (5 cases) and systemic lupus
      erythematosus (2 cases). Seven cases had been observed in the past four years,
      four of these in 2000. One patient developed disseminated disease and two
      patients died. In the era of HIV/AIDS and due to the fact that HIV-infected
      children are tending to live longer, we may encounter a higher occurrence of this
      opportunistic fungus in children.

PMID- 11529386
TI  - The value of methemoglobin reduction test as a screening test for neonatal
      glucose 6-phosphate dehydrogenase deficiency.
AB  - Glucose 6-phosphate dehydrogenase (G-6-PD) deficiency is common in the Thai
      population and is the cause of neonatal hyperbilirubinemia and hemolytic anemia.
      This X-linked disorder is much more common in males than females. The objectives
      of this study were to compare the result of the screening methemoglobin reduction
      test (MRT) with the gold standard G-6-PD activity, and also to determine the
      prevalence of G-6-PD deficiency in the cord blood and blood of neonates with
      hyperbilirubinemia. Five hunderd and twenty two randomly selected cord blood (350
      males, 172 females) and 229 peripheral blood from neonates with
      hyperbilirubinemia were assayed for G-6-PD enzyme activity using a WHO
      recommended standard test as well as methemoglobin reduction (MR) test. The
      results showed that prevalence of G-6-PD deficiency from the cord blood was 11.1
      per cent in males, and 5.59 per cent in females. Among newborns with neonatal
      jaundice, the prevalence of G-6-PD deficiency was 22.1 per cent in males and 10.1
      per cent in females. MRT in cord blood G-6-PD deficiency screening had acceptable
      sensitivity (85.7%) and high specificity (98.1%). The sensitivity of MRT in
      jaundiced infants was low (60.0%) whereas the specificity was acceptable (92.1%).
      The negative predictive values were more than 90 per cent while the positive
      predictive values were low (61-65%) from both specimens. CONCLUSIONS: G-6-PD
      deficiency is common in the Thai population, both in males and females and can be
      screened from cord blood by using low cost MRT. G-6-PD deficiency contributes to
      20 per cent of neonatal jaundice, and screening with MRT yields low sensitivity.

PMID- 11529387
TI  - Molecular cloning of phospholipase A2 from a Thai Russell's viper venom gland
      cDNA library.
AB  - Snake venom contains several toxins. Russell's viper (D. russellii, RV) is a
      venomous snake prevalent in northern and central Thailand. RV bites can cause
      disseminated coagulation, hemolysis, and edema of the bitten limbs. To identify
      protein components of RV venom, we made a cDNA library from RV venom glands, and
      randomly sequenced cloned cDNA. We were able to clone a cDNA encoding RV
      phospholipase A2 (PLA2). PLA2 is an active enzyme found in several species of
      snake venom worldwide. PLA2 is thought to be toxic to cell membrane, thereby, can
      cause local cell and tissue damage, as well as systemic effects in snake bite
      victims. This PLA2 cDNA clone would facilitate in vivo studies of the
      pathophysiology of RV bite.

PMID- 11529388
TI  - Predictors of depression in geriatric medically ill inpatients.
AB  - OBJECTIVE: Depression in medically ill inpatients has been associated with
      increased morbidity and mortality. The purpose of this study was to identify
      variables that would successfully predict depression in this population. METHODS:
      The sample consisted of 314 male, medically ill veterans, age 60 and older,
      admitted to the acute medical service at Baltimore Veteran Administration Medical
      Center. Sixty of 314 patients met criteria for Major Depression and scored 11 or
      higher on the Geriatric Depression Scale. Variables assessing age, race, social
      support, severity of illness, degree of functional disability, life satisfaction,
      and hopelessness were included in a logistic regression analysis as predictors of
      depression. RESULTS: The variables that significantly predicted depression were
      derived from the Beck Hopelessness Scale, Life Satisfaction Score, and the
      Cumulative Illness Rating Score. CONCLUSIONS: The results indicated that
      medically ill inpatients who feel hopeless about the future, feel the best years
      of their lives are behind them, and have serious medical problems are likely to
      be clinically depressed.

PMID- 11529389
TI  - The utility of the CES-D as a depression screening measure among low-income women
      attending primary care clinics. The Center for Epidemiologic Studies-Depression.
AB  - OBJECTIVE: Depressive disorders are among the most common medical disorders seen
      in primary care practice. The Center for Epidemiologic Studies-Depression (CES-D)
      scale is one of the measures commonly suggested for detecting depression in these
      clinics. However, to our knowledge, there have been no previous studies examining
      the validity of the CES-D among low-income women attending primary care clinics.
      METHOD: Low-income women attending public primary care clinics (n = 179, ages 20
      77) completed the CES-D and the Diagnostic Interview Schedule for the DSM-IV (DIS
      IV). RESULTS: The results supported the validity of the CES-D. The standard cut
      score of 16 and above yielded a sensitivity of .95 and specificity of .70 in
      predicting Major Depressive Disorder (MDD). However, over two-thirds of those who
      screened positive did not meet criteria for MDD (positive predictive value =
      .28). The standard cut-score appears valid, but inefficient for depression
      screening in this population. An elevated cut-score of 34 yielded a higher
      specificity (.95) and over 50 percent of the patients who screened positive had a
      MDD (positive predictive value = .53), but at great cost to sensitivity (.45).
      CONCLUSION: Results indicated that the CES-D appears to be as valid for low
      income, minority women as for any other demographic group examined in the
      literature. Despite similar validity, the CES-D appears to be inadequate for
      routine screening in this population. The positive predictive value remains very
      low no matter which cut-scores are used. The costs of the false positive rates
      could be prohibitive, especially in similar public primary care settings.

PMID- 11529390
TI  - Persons with depressive symptoms and the treatments they receive: a comparison of
      primary care physicians and psychiatrists.
AB  - OBJECTIVE: To determine if demographic differences exist in patients with
      depressive symptoms as the principal reason for visits to primary care physicians
      (PCP) versus psychiatrists. To estimate the likelihood of these patients
      receiving a range of mental health services from each provider group. METHODS:
      Review and analysis of all outpatient visits made by patients with depressive
      symptoms using the National Ambulatory Medical Care Surveys (NAMCS) conducted in
      1995 and 1996. RESULTS: A significantly greater proportion of visits by persons
      with depressive symptoms as the principal reason for visit were made to
      psychiatrists than to primary care physicians (T = -3.56, p = .000). However,
      men, African-Americans, other Non-White persons, and persons aged 65 to 74 and 75
      years and over were proportionately more likely to visit a PCP than a
      psychiatrist. Women, whites, and persons aged 45 to 64 were proportionately more
      likely to make a visit to a psychiatrist than to a PCP. The overall intensity of
      care delivered by PCPs for patients with depressive symptoms was significantly
      lower than that provided by psychiatrists (t = -2.03, p = .02). Analysis of
      individual services also revealed significant differences in service provision.
      CONCLUSIONS: Demographic differences among the patient caseloads of these
      physician groups have implications for mental health service delivery because of
      known distinctions in prevalence rates, symptom presentation, and functionality
      among depressed patient subgroups.

PMID- 11529391
TI  - A comparison of self-concept and personality disorders in women with pain
      accounted for by psychological factors, women with major depression, and healthy
      controls.
AB  - OBJECTIVE: Do patients with pain accounted for by psychological factors (P)
      differ in their self-concept and personality disorders from patients with major
      depression (D) and healthy controls (C)? METHOD: Thirty hospitalized P-patients
      (DSM-IV, 307.80) and 30 hospitalized D-Patients (DSM-III-R) were given the Beck
      Depression Inventory on admission (BDI-1) and at discharge (BDI-2). Together with
      BDI-2, patients filled out the Personality Disorder Questionnaire for DSM-III-R
      (PDQR) and the Frankfurt Self-Concept Scales (FSKN). Thirty-two healthy
      comparisons (C) completed the same questionnaires. RESULTS: BDI-2 showed no
      significant differences between groups P and D, a prerequisite for the comparison
      of psychological traits. PDQR differed in the three groups. D showed more
      dependent, obsessive-compulsive, and histrionic personality features than group
      P. The three groups differed in FSKN total score and all 10 subscales (C
      (healthiest self-concept) > P > D). Groups P and D were different (P > D) in
      total score and subscales: performance, problem coping, confidence in behavior
      and decision taking, and self-esteem. Ten P-patients with pathological BDI-2
      (P(D)) had significantly more disturbed PDQR and FSKN scores than the non
      depressed (P(ND)), and closely resembled the D-patients. CONCLUSIONS: Personality
      disorders and self-concept are not homogenous in female patients with P. Subgroup
      P(ND) differs from patients with depression (fewer personality disorders, better
      self-concept), whereas subgroup P(D) closely resembles them.

PMID- 11529392
TI  - Chronic pain presenting as major depression in a cross-cultural setting.
AB  - We report on a female African immigrant who developed chronic pain as a
      consequence of osteomalacia. Due to cultural particularities in pain expression,
      her symptoms were first attributed to a major depressive episode. Cultural
      factors influencing pain perception and expression are reviewed. The importance
      of working with competent interpreters in cross-cultural settings is emphasized.

PMID- 11529393
TI  - Religion and mental health among women veterans with sexual assault experience.
AB  - OBJECTIVE: Religion has been shown to have a positive impact on well-being and to
      play an important role in coping with stressful life events. However, the
      buffering effect of religiosity on mental health, after a particularly stressful
      life event such as sexual assault, has not been studied. In this study we
      examined the buffering effect of religion on mental health and depression for
      women who report experiencing sexual assault while in the military. METHOD: The
      sample includes a nationally representative sample of 3,543 women veterans who
      use VA ambulatory care. Two dimensions of religiosity were used: organizational
      (frequency of religious service attendance) and subjective (the extent religious
      beliefs are a source of strength/comfort). Mental health was measured by the
      mental component summary (MCS) from the SF36 and depressive symptoms were
      measured by the Center for Epidemiologic Studies-Depression (CES-D) scale.
      RESULTS: Women veterans who reported experiencing sexual assault while in the
      military had lower mental health scores and higher levels of depression. Linear
      regression analysis indicated that these negative impacts diminished with
      increased frequency of religious service attendance, supporting the buffering
      effect of organizational religiosity on mental health and depression. Although
      the buffering effect of subjective religiosity was not evident, subjective
      religiosity was shown to be positively associated with better mental health in
      both groups of women with and without sexual assault experience in the military.
      CONCLUSIONS: Frequent religious service attendance buffers the negative impacts
      of sexual assault on mental health and depression of women veterans. The
      potential of integrating religiosity in designing interventions is discussed.

PMID- 11529394
TI  - The prevalence of psychiatric disorders and subsyndromal mental illness in low
      income, medically ill elderly.
AB  - OBJECTIVE: This study estimated the past and current prevalence of psychiatric
      illness and subsyndromal mental illness (both pre-relapse and new onset) in a
      sample of low-income, medically ill older adults. METHOD: A convenience sample of
      95 public sector medical patients aged 55 and older were assessed for the
      presence of psychiatric diagnosis and symptoms using the Geriatric Depression
      Scale, Beck Anxiety Inventory, the Short Michigan Alcohol Screening Test, and the
      Computerized Diagnostic Interview Schedule (DIS-C). RESULTS: Dysthymia and Major
      Depression were the most prevalent current disorders and Alcohol Dependence the
      most prevalent past disorder. Overall, 25 percent met criteria for at least one
      Axis I disorder. An additional 44 percent of patients had subsyndromal mental
      illness: 14 percent had subsyndromal depression, 17 percent were significantly
      anxious, and 30 percent were problem drinkers. A prior model predicting current
      Axis I disorder in younger people was found to be predictive of current Axis I
      but did not predict to subsyndromal disorder. CONCLUSIONS: The rates of
      psychiatric disorders and symptoms in this older, low-income population were
      similar to those in other samples of older medical patients. The findings from
      this research suggest the need for larger epidemiological studies of the
      prevalence of psychiatric disorders in this disadvantaged aging population. The
      complexities of this type of research are also discussed.

PMID- 11529395
TI  - Religion and medicine II: religion, mental health, and related behaviors.
AB  - In this second in a series of articles on religion and medicine, I focus on the
      relationship between religion and mental health. This discussion is based on a
      comprehensive and systematic review of a century of research examining religion's
      relationship to mental health, social support, substance abuse, and other
      behaviors affecting mental or social functioning. This review includes over 630
      separate data-based reports that focus on religion and well-being, hope and
      optimism, meaning and purpose, depression, suicide, anxiety, psychosis, social
      support and marital stability, alcohol and drug abuse, cigarette smoking, extra
      marital sexual behaviors, and delinquency. Reasons for the associations found are
      discussed and conclusions drawn in light of the findings.

PMID- 11529396
TI  - Isolated growth hormone deficiency in children and adolescents.
AB  - Although it is difficult to reach international agreement on the definition of
      growth hormone deficiency (GHD) in children and adolescents, great efforts to do
      so have been made during the last two decades. A somewhat limited definition of
      GHD is: a combination of auxological, clinical, biochemical and metabolic
      abnormalities caused by lack or insufficiency of GH secretion that results in a
      decrease in the production of GH-dependent hormones and growth factors. Its
      aetiology is very complex. Therefore, specific studies must be performed during
      different periods of childhood (neonatal, prepubertal and pubertal periods).
      Auxological parameters, particularly growth velocity (GV), are still considered
      the best clinical measures for analysing human growth. The spectacular advances
      in our understanding of molecular biology during the past twenty years have
      allowed, and will continue to allow, a more and more precise diagnosis of the
      molecular anomalies of human growth. This will, in turn, allow changes caused by
      genetic lesions to be more efficiently distinguished from those due to
      nutritional, organic, tumoural, psychological or traumatic causes. Our knowledge
      of the molecular bases of undergrowth due to a deficiency in GH has developed as
      a result of the localisation and characterisation of human genes which code for
      proteins implicated in the hormonal regulation of growth. These genes include
      pituitary GH (GH1), pituitary transcription factor 1 (Pit-1), the prophet of Pit
      1 (PROP-1), the pituitary transcription factor LHX3, the transcription factor
      HESX1 and the GH-releasing hormone receptor (GHRHr). In addition, magnetic
      resonance imaging is the best available imaging method for the evaluation of size
      and structure of the pituitary and the parasellar region.

PMID- 11529397
TI  - Multiple pituitary hormone deficiency: management of puberty for optimal
      auxological results.
AB  - The overview in this paper focuses on ways of achieving optimal auxological
      results in puberty, principally in idiopathic and congenital multiple pituitary
      hormone deficiency (MPHD), suggested by the co-authors. We agreed that diagnosing
      gonadotrophin insufficiency/deficiency is difficult in young children and should
      be repeated in late prepuberty, but a firm diagnosis of MPHD helps avoid
      endocrine re-testing at the end of growth. The hypothalamic-pituitary axis must
      be reassessed periodically in evolving endocrinopathies, though current practice
      varies widely. Optimum age to induce puberty is 11-12 years in girls and 13-14
      boys, and sex steroids are the preferred agents. Short-course testosterone to
      increase micropenis size is advantageous, but inducing early testicular
      maturation is not known to improve later fertility. There is also little evidence
      for increasing the dose of GH during puberty, though therapy should continue to
      final height, and possibly until peak bone mass is achieved. Delaying puberty is
      an option in septo-optic dysplasia, and minimising the dose of hydrocortisone is
      crucial in treating ACTH/cortisol insufficiency. Many unresolved questions remain
      in this difficult area.

PMID- 11529398
TI  - Factors determining final height in congenital adrenal hyperplasia.
AB  - Congenital adrenal hyperplasia (CAH) is a family of adrenal disorders whereby
      cortisol biosynthesis is impaired or abolished. In most cases, CAH is caused by a
      deficiency of the enzyme 21-hydroxylase causing a massive build up of adrenal
      precursors. In addition to prenatal virilisation of genetic females and postnatal
      virilisation of both males and females, short adult stature is characteristic of
      the disorder. The inadequate final height in CAH patients is often attributed to
      overtreatment with glucocorticoid replacement and poor control of adrenal
      androgen levels. In a recent study, the use of growth hormone alone and in
      combination with gonadotropin releasing hormone analogue in children with CAH and
      poor predicted final height was found to decrease height deficit after one and
      two years of treatment.

PMID- 11529399
TI  - Management of puberty for optimal auxological results in beta-thalassaemia major.
AB  - Short stature is present in a significant percentage of patients affected by beta
      thalassaemia major. Growth failure of patients with thalassaemia is
      multifactorial. The most important contribution is attributed to the toxic effect
      of desferrioxamine and to endocrine disorders, due to iron overload. The
      commonest endocrine complication is hypogonadism. The growth pattern of patients
      with thalassaemia is characterized by normal growth during childhood, a
      deceleration of growth velocity around age 9-10 years, and a reduced pubertal
      growth spurt. In addition, reduced growth of the trunk is often present. Short
      stature and short trunk are more evident at pubertal age. Hypogonadism is usually
      considered responsible for the pubertal growth failure, as well as the
      aggravation of body disproportion at pubertal age. However, data suggest that
      pubertal height gain and final height are reduced in both patients with
      spontaneous puberty and patients with induced puberty. It is concluded that
      several aspects of peripubertal growth in patients with thalassaemia remain to be
      clarified.

PMID- 11529400
TI  - Unresolved problems concerning optimal therapy of puberty in children with
      chronic renal diseases.
AB  - Many children with chronic renal insufficiency (CRI) show growth retardation and
      severely delayed pubertal development. Successful renal transplantation (RTx)
      also rarely results in full growth rehabilitation. Pubertal height gain in CRI
      patients is only 58% and 48% of that observed in late-maturing boys and girls,
      respectively. Growth retardation in both CRI and RTx patients is not the result
      of abnormal GH secretion or decreased levels of IGF-I, but rather of elevated
      levels of IGFBPs inhibiting the bioavailability of the IGFs. In RTx patients
      prednisone may also inhibit growth directly via inhibition of bone matrix
      formation. Several studies have convincingly shown that GH therapy at a dose of 4
      IU/m2/day results in a sustained improvement of growth in prepubertal and
      pubertal children with CRI and in growth-retarded prepubertal and pubertal post
      transplant patients. The following consensus was reached concerning optimal
      therapy of puberty in children with chronic renal disease. GH therapy does not
      lead to an earlier start of puberty. It is safe to give GH to RTx patients if
      transplant function is stable. GH therapy will not accelerate bone maturation and
      can improve the final height of children with CRI and after RTx. Increasing the
      GH dose above 4 IU/m2/day in pubertal RTx patients does not increase height gain
      or final height and is not advised as it may increase insulin resistance. GH
      should best be started before the start of the pubertal growth spurt but will
      still be effective in RTx patients with advanced bone age. GH testing should not
      be a prerequisite for starting GH therapy. It is important to optimise other
      therapies during puberty. During GH therapy of RTx patients use minimum daily,
      not alternate-day, steroid dosing. Further research is still required on the
      possible long-term effects of GH therapy in children with chronic diseases. Two
      studies demonstrated improved long-term growth and final height within the target
      height range, without significant side effects. Renal graft function did not
      deteriorate more than in matched controls. A GH dose of 4 IU/m2/day proved
      adequate.

PMID- 11529401
TI  - Management of puberty in constitutional delay of growth and puberty.
AB  - Constitutional delay of growth and puberty (CDGP) is the most common presenting
      form of short stature, but no single test can infallibly discriminate CDGP and
      isolated hypogonadotrophic hypogonadism. Management of puberty in CDGP aims to
      optimise not only growth maintaining body proportions and improving peak bone
      mass without impairing growth potential--but also well-being; for example, the
      distress boys often suffer because of their lack of growth and pubertal
      progression can affect their school performance and social relationships. Typical
      sex steroid treatments to induce puberty in boys with CDGP include testosterone
      (T) enanthate, T undecanoate, mixed T esters, T transdermal patches, and
      oxandrolone p.o. Compared with other regimens, short-course low-dose depot T i.m.
      is an effective, practical, safe, well tolerated, and inexpensive regimen. Some
      unresolved problems in management include optimal timing and dose of sex steroid
      treatment, the role of GH in CDGP, and the management of CDGP in girls.

PMID- 11529402
TI  - Turner's syndrome.
AB  - Turner syndrome (TS) is the most common sex-chromosome abnormality in females.
      Short stature and hypogonadism are the classical clinical findings. The
      spontaneous final height (FH) ranges between 139 and 147 cm, representing a
      growth deficit of about 20 cm with respect to the unaffected population. GH
      therapy improves FH and should be started during childhood at a high dose of
      about 1 IU/kg/week (range 0.6-2 IU/kg/week). Some authors advocate combined
      therapy with an anabolic steroid at various doses (e.g. oxandrolone 0.05-0.1
      mg/kg/day). This treatment results in a significantly increased FH, a large
      proportion of treated girls reaching a FH of more than 150 cm. Gonadal function
      is compromised during adolescence in about 80% of girls with TS, whilst in about
      20% pubertal development occurs spontaneously. Oestrogen therapy should be
      started at the age of 13-14 years in hypogonadic patients; early onset of
      treatment (before 12 years) seems to compromise FH. Other concerns in these
      patients are fertility and osteopenia.

PMID- 11529403
TI  - Idiopathic short stature.
AB  - Idiopathic short stature (ISS) is a term used to describe the status of children
      with short stature that cannot be attributed to a specific cause. Many children
      diagnosed as having ISS have partial GH insensitivity, which can result from
      disturbances at various points of the GH-IGF-I axis. Several clinical studies on
      spontaneous growth in ISS showed that adult height was almost in the range of
      target height. GH treatment led to adult height not significantly higher than the
      pretreatment predicted adult height in most reports. No metabolic side effects
      have been observed, even when the dose was higher than in GH deficiency.
      Manipulation of puberty with gonadotrophin releasing hormone analogues reported
      by a few authors in a small number of children has shown conflicting results.
      Long-term psychological benefits of GH therapy for short normal children have not
      been demonstrated to date.

PMID- 11529404
TI  - Current concepts in tall stature and overgrowth syndromes.
AB  - In this overview an update is given on the pathogenesis, classification and
      differential diagnosis of overgrowth syndromes. In addition, height prognosis and
      therapeutic modalities available for managing mainly constitutional tall stature
      are discussed. Constitutional tall stature comprises normal variants in which one
      or both parents are tall. Primary disorders may have a prenatal onset and may be
      of chromosomal or genetic origin. Secondary overgrowth syndromes are most often
      the result of hormonal disturbances. Height prediction plays a key role in the
      management of tall children. Prediction equation models have been developed based
      on the growth data of healthy tall children. There is general agreement that a
      favourable effect on reducing ultimate height is obtained using high doses of sex
      steroids (girls 100-300 microg ethinyloestradiol; boys testosterone (T) ester
      depot preparations 250-1000 mg/month), the height reduction being greater when
      the treatment is started at a lower chronological and/or bone age. An alternative
      is the induction of puberty with low doses of sex steroids (girls 5-50 microg
      ethinyloestradiol; boys T esters 25-50 mg/m2/3 wk). In addition orthopaedic
      procedures have been suggested, but there is limited experience. Although
      psychosocial factors constitute the main reason for treating tall stature,
      extensive psychological investigations before or during height limiting therapy
      are lacking. Moreover, there are no objective data indicating lifelong
      psychosocial damage resulting from being tall.

PMID- 11529405
TI  - Optimal therapy of pubertal disorders in precocious/early puberty.
AB  - GnRHa have been used in the treatment of central precocious puberty (CPP) for a
      decade and some final results of this therapy are now available. Treatment
      preserves height potential in younger patients and a complete recovery of the
      hypothalamic-pituitary-gonadal axis occurs at the end of treatment. However, some
      aspects of the management of CPP are still debated. Probably the age limits
      between normal and precocious puberty have to be lowered, and new diagnostic
      tools will modify and simplify diagnostic criteria. The possibility of
      progression of premature thelarche into precocious puberty, the pathogenesis of
      organic and idiopathic precocious puberty, the criteria for decision to treat and
      to stop treatment and the utility of an association with GH treatment will be
      better understood in the future. Follow-up of patients after stopping therapy
      includes frequency and characteristics of menses, the possible higher incidence
      of polycystic ovary-like syndrome and the correct achievement of a normal peak
      bone mass and body composition. In this review we discuss some of these points,
      with particular attention to precocious puberty in girls.

PMID- 11529406
TI  - Unresolved problems in optimal therapy of pubertal disorders in oncological and
      bone marrow transplanted patients.
AB  - Specialised clinics for the long-term follow-up of survivors from childhood
      cancer have developed over recent years. The problems encountered among patients
      who received multiple chemotherapy and radiotherapy can be challenging and
      require high expertise and close collaboration among different professionals
      (e.g. oncologists, endocrinologists, radiotherapists, psychologists). Endocrine
      disorders are often seen, particularly among those who received cranial
      radiotherapy or gonadotoxic chemotherapy; puberty can be affected and the
      spectrum of disorders may range from precocious or accelerated puberty to
      delayed, arrested or even absent pubertal development. Growth impairment can be
      multifactorial and growth hormone deficiency is an important but probably not the
      only factor involved. Many questions remain about the optimal management of this
      group of young patients. In the consensus guidelines that follow the overview an
      attempt is made to help optimise patients' growth and puberty by suggesting
      practical clinical approaches to some of the most challenging issues.

PMID- 11529407
TI  - Achalasia cardia: uncommon presentation.

PMID- 11529408
TI  - Pulmonary mucoraceous fungal ball.
AB  - A case of opportunistic pulmonary infection in the form of fungal ball produced
      by the family of mucoraceae in the class of phycomycetes having nonseptate hyphae
      (cellophane tubules) with haphazard branching in a post-tubercular
      immunocompetent patient is described. Clinical course was chronic with right
      upper lobe cavity invaded by fungi of mucor species, pathology was granuloma with
      blood vessel thrombosis, and a fungus ball. The host had no associated
      predisposing diseases. Segmental resectional surgery of the right upper lobe
      along with removal of fungus ball under the coverage of modified dose of
      amphotericin B was performed. Literature scanning revealed rarity of mucormycosis
      in immunocompetent host.

PMID- 11529409
TI  - Intrapericardial teratoma masquerading as pyopericardium.
AB  - A 10-year-old boy was admitted with cardiac tamponade. Initial pericardiocentasis
      yielded pus. A subxiphoid tube-pericardiostomy was done and thick, purulent
      material was drained out. Subsequently, pericardiectomy was undertaken as
      features of pericardial constriction persisted. At surgery, however, an
      intrapericardial mass was discovered. Successful excision was performed and the
      patient made an uneventful recovery. Histopathology of the mass revealed features
      of an intrapericardial teratoma. Rarity of the lesion, and a hitherto unreported
      mode of presentation make this case worthy of documentation.

PMID- 11529410
TI  - Non responding pneumonia with skin lesions.
AB  - Sweet's syndrome (acute febrile neutrophilic dermatitis) is characterised by
      classical skin lesions accompanied by fever and malaise. Systemic involvement may
      be present and lung involvement in Sweet's syndrome has been reported in the form
      of bilateral pulmonary infiltrates, bronchiolitis obliterans organising pneumonia
      and pleural effusion. There are dense papillary neutrophilic infiltrates on
      histopathology. We present a case of Sweets' syndrome with left lower lobe
      consolidation and persistent fever which was non-responsive to antibiotics but
      showed clinical improvement with clearing of radiological opacities on oral
      steroid therapy.

PMID- 11529411
TI  - Primary tuberculosis of soft palate.
AB  - Primary tuberculosis of upper respiratory tract including oral cavity is a rare
      disease. One such unusual case is reported.

PMID- 11529412
TI  - Sleep disordered breathing and hypertension: time to wake up!

PMID- 11529413
TI  - Purification and characterization of a 31 kDa mycobacterial excretory-secretory
      antigenic protein with a diagnostic potential in pulmonary tuberculosis.
AB  - Proteins secreted into the culture medium by Mycobacterium tuberculosis are shown
      to be a source of antigens of immunodiagnostic importance. In our earlier study,
      we had reported a 31-37 kDa seroreactive gel-eluted antigenic fraction (ESAS-7),
      isolated from culture filtrate proteins of Mycobacterium tuberculosis H37Ra. In
      this report, we describe further purification of excretory-secretory ESAS-7
      antigen fraction by fast protein liquid chromatography (FPLC) on Resource 'S'
      cation-exchange column and isolation of a more active and purified protein
      antigen fraction ESAS-7F. ESAS-7F antigen was characterized as a 31 kDa molecular
      weight glycoprotein containing a metallo-serine protease activity. N-terminal
      sequence analysis showed the first five amino acids as NTGQS (Asp-Thr-Gly-Glu
      Ser). The present study helped in the isolation of a well characterized 31 kDa
      mycobacterial glycoprotein antigen with protease activity and diagnostic
      potential in detection of tuberculosis infection.

PMID- 11529414
TI  - Awareness about the disease in asthma patients receiving treatment from
      physicians at different levels.
AB  - Morbidity and mortality due to asthma continue to increase worldwide. One of the
      reasons is an inadequate patient awareness regarding the disease and its
      treatment. One thousand four hundred patients with reversible airflow obstruction
      due to bronchial asthma were included in this study and assigned to one of the
      four groups depending on whom they had consulted before. The patients were asked
      to complete a questionnaire which included questions regarding the disease, its
      course, understanding of treatment schedules, correct use of inhaler devices, use
      of peak flow meter and when to take emergency actions. The awareness regarding
      the disease, avoidance of trigger factors, treatment adherence, and correct use
      of inhaler devices was found to be greater in patients who had received initial
      treatment from a qualified physician and was best among those treated at the
      Institute level. The use of peak flow meter by the patients for objective
      assessment of asthma and the awareness regarding use of emergency care services
      was found to be poor among all the groups. To improve patient awareness and
      quality of asthma care delivery, private practitioners as well as Institute
      doctors must be included in continuing medical education programmes and various
      methods of communications with patients should be used along with separate
      clinics for asthma at the Institute level.

PMID- 11529415
TI  - Static lung mechanics in patients of progressive systemic sclerosis without
      obvious pulmonary involvement.
AB  - Pulmonary fibrosis is a common complication in progressive systemic sclerosis
      (PSS). Physical examination and/or routine pulmonary function tests can, however,
      detect only relatively advanced disease. We assessed the utility of static lung
      pressure-volume analysis in detecting lung involvement in patients of PSS without
      obvious clinical, radiological or spirographic evidence of pulmonary disease.
      Static lung volumes were determined and expiratory lung pressure-volume
      measurements were obtained in 10 patients with PSS, using a computerized whole
      body plethysmograph. Static pressure-volume data was also subjected to
      monoexponential analysis. All patients had normal total lung capacity. Three
      patients had reduced static compliance, of whom one also had reduced value for
      the shape constant K (calculated from exponential analysis of pressure-volume
      data). Examination of pressure volume curve showed a pattern consistent with
      interstitial fibrosis in these patients. We conclude that detailed study of lung
      mechanics can help identify early pulmonary involvement in patients with PSS.

PMID- 11529416
TI  - 13C spin-lattice relaxation in natural diamond: Zeeman relaxation at 4.7 T and
      300 K due to fixed paramagnetic nitrogen defects.
AB  - 13C spin-lattice relaxation times in the laboratory frame, ranging from 1.4 to 36
      h, have been measured on a suite of five natural type Ia and Ib diamonds at 4.7 T
      and 300 K. Each of the diamonds contains two types of fixed paramagnetic centers
      with overlapping inhomogeneous electron paramagnetic resonance (EPR) lines. EPR
      techniques have been employed to identify these defects and to determine their
      concentrations and relaxation times at X-band. Spin-lattice relaxation behavior
      of 13C in diamonds containing paramagnetic P1, P2, N2. and N3 centers are
      discussed. Depending on the paramagnetic impurity types and concentrations
      present in each diamond, three different nuclear spin-lattice relaxation (SLR)
      paths exist, namely that due to electron SLR mechanisms and two types of three
      spin processes (TSPs). The one three-spin process (TSP1) involves a simultaneous
      transition of two electron spins belonging to the same hyperfine EPR line and a
      flip of a 13C spin, while the other process (TSP2) involves two electron spins
      belonging to different hyperfine EPR lines and a 13C spin. It is shown that the
      thermal contact between the 13C nuclear Zeeman and electron dipole-dipole
      interaction reservoirs is field dependent, thus forming a bottleneck in the 13C
      relaxation path due to TSP1 at high magnetic fields.

PMID- 11529417
TI  - 59Co chemical shift anisotropy and quadrupole coupling for K3Co(CN)6 from MQMAS
      and MAS NMR spectroscopy.
AB  - 59Co triple-quantum (3Q) MAS and single-pulse MAS NMR spectra of K3Co(CN)6 have
      been obtained at 14.1 T and used in a comparison of these methods for
      determination of small chemical shift anisotropies for spin I = 7/2 nuclei. From
      the 3QMAS NMR spectrum a spinning sideband manifold in the isotropic dimension
      with high resolution is reconstructed from the intensities of all spinning
      sidebands in the 3QMAS spectrum. The chemical shift anisotropy (CSA) parameters
      determined from this spectrum are compared with those obtained from MAS NMR
      spectra of (i) the complete manifold of spinning sidebands for the central and
      satellite transitions and of (ii) the second-order quadrupolar lineshapes for the
      centerband and spinning sidebands from the central transition. A good agreement
      between the three data sets, all of high precision, is obtained for the shift
      anisotropy (delta(sigma) = delta(iso) - delta(zz)) whereas minor deviations are
      observed for the CSA asymmetry parameter (eta(sigma)). The temperature dependence
      of the isotropic 59Co chemical shift has been studied over a temperature range
      from -28 to +76 degrees C. A linear and positive temperature dependence of 0.97
      ppm/degree C is observed.

PMID- 11529418
TI  - 13C cross-polarization MAS NMR study of some steroidal sapogenins.
AB  - Cross-polarization (CP) magic angle spinning (MAS) solid-state 13C NMR spectra of
      five steroidal sapogenins: tigogenin ((25R)-5alpha-spirostan-3beta-ol), hecogenin
      (3beta-hydroxy-(25R)-5alpha-spirostan-12-one), diosgenin ((delta5-(25R)-5alpha
      spirosten-3beta-ol), sarsasapogenin ((25S)-55beta-spirostan-3beta-ol), and
      smilagenin ((25R)-5beta-spirostan-3beta-ol) were recorded. The solid-state
      chemical shifts are almost the same as for solution, which indicate that
      confirmations of sapogenins are similar in both phases. The doubling of some
      resonances in the spectra of solid diosgenin shows that there are two molecules
      in the crystallographic asymmetric unit. The cross-polarization time constants
      T(CP) and relaxation times in the rotating frame T(1rho)H were obtained from the
      variable-contact cross-polarization experiments for tigogenin and diosgenin. The
      values of T(CH) for methyl carbons indicate fast rotation of methyl groups and
      are close (0.30-0.35 ms), suggesting that the interaction with their
      intramolecular neighbors is similar. The values of T(1rho)H for carbons of
      tigogenin are longer than of diosgenin. Very efficient cross-polarization
      dynamics results in short time required for obtaining a spectrum of sapogenin of
      remarkably good quality.

PMID- 11529419
TI  - 17O NMR studies of low silicate zeolites.
AB  - Multiple-quantum magic-angle spinning and double-rotation NMR techniques were
      applied in the high field of 17.6 T to the study of oxygen-17-enriched zeolites A
      and LSX with the ratio Si/Al = 1. A monotonic correlation between the isotropic
      value of the chemical shift and the Si-O-Al bond angle alpha (taken from X-ray
      data) could be found. Hydration of the zeolites causes a downfield 17O NMR
      chemical shift of about 8 ppm with respect to the dehydrated zeolites. Ion
      exchange of the hydrated zeolites generates stronger chemical shift effects. The
      increase of the basicity of the oxygen framework of the zeolite LSX is reflected
      by a downfield shift of approx. 10 ppm going from the lithium to the cesium form,
      and the substitution of sodium by thallium in the zeolite A causes a shift of 34
      ppm for the O3 signal. 17O DOR NMR spectra are superior to 17O 3QMAS NMR spectra,
      featuring a resolution increase by a factor of 2 and are about equal with respect
      to the sensitivity. The residual linewidths of the signals in the 17O DOR and 17O
      5QMAS NMR spectra can be explained by a distribution of the Si-O-Al angles in the
      zeolites.

PMID- 11529420
TI  - Magnetic susceptibility effects on 13C MAS NMR spectra of carbon materials and
      graphite.
AB  - 13C high-resolution solid-state nuclear magnetic resonance (NMR) was employed to
      study carbon materials prepared through the thermal decomposition of four
      different organic precursors (rice hulls, endocarp of babassu coconut, peat, and
      PVC). For heat treatment temperatures (HTTs) above about 600 C, all materials
      presented 13C NMR spectra composed of a unique resonance line associated with
      carbon atoms in aromatic planes. With increasing HTT a continuous broadening of
      this resonance and a diamagnetic shift in its central frequency were verified for
      all samples. The evolution of the magnitude and anisotropy of the magnetic
      susceptibility of the heat-treated carbon samples with HTT explains well these
      findings. It is shown that these results are better understood when a comparison
      is made with the features of the 13C NMR spectrum of polycrystalline graphite,
      for which the magnetic susceptibility effect is also present and is much more
      pronounced.

PMID- 11529421
TI  - Background signal in solid state 13C NMR spectra of soil organic matter (SOM)
      quantification and minimization.
AB  - 13C background signal, obtained for an empty rotor, was shown by spin counting
      experiments to be equivalent to 1 mg of observable carbon for cross-polarization
      (CP) spectra and 69 mg of observable C for Bloch decay (BD) spectra. The BD
      background was mainly due to Kel-F in the stator. with minimal signal detected
      from the Kel-F end-caps. The CP background was attributed to non-Kel-F components
      of the stator, probe, or probe supports. The BD background signal was eliminated
      by using a modified dipolar dephasing pulse sequence in which the absence of 19F
      decoupling (rather than the absence of 1H decoupling) causes selective
      elimination of the Kel-F signal.

PMID- 11529422
TI  - Function word repetitions emerge when speakers are operantly conditioned to
      reduce frequency of silent pauses.
AB  - Beattie and Bradbury (1979) reported a study in which, in one condition, they
      punished speakers when they produced silent pauses (by lighting a light they were
      supposed to keep switched off). They found speakers were able to reduce silent
      pauses and that this was not achieved at the expense of reduced overall speech
      rate. They reported an unexpected increase in word repetition rate. A recent
      theory proposed by Howell, Au-Yeung, and Sackin (1999) predicts that the change
      in word repetition rate will occur on function, not content words. This
      hypothesis is tested and confirmed. The results are used to assess the theory and
      to consider practical applications of this conditioning procedure.

PMID- 11529423
TI  - Loose but normal: a semantic association study.
AB  - An abnormal facilitation of the spreading activation within semantic networks is
      thought to under-lie schizophrenics' remote associations and referential ideas.
      In normal subjects, elevated magical ideation (MI) has also been associated with
      a style of thinking similar to that of schizotypal subjects. We thus wondered
      whether normal subjects with a higher MI score would judge "loose associations"
      as being more closely related than do subjects with a lower MI score. In two
      experiments, we investigated whether judgments of the semantic distance between
      stimulus words varied as a function of MI. In the first experiment, random word
      pairs of two word classes, animals and fruits, were presented. Subjects had to
      judge the semantic distance between word pairs. In the second experiment, sets of
      three words were presented, consisting of a pair of indirectly related, or
      unrelated nouns plus a third noun. Subjects had to judge the semantic distance of
      the third noun to the word pair The results of both experiments showed that
      higher MI subjects considered unrelated words as more closely associated than did
      lower MI subjects. We conjecture that for normal subjects high on MI "loose
      associations" may not be loose after all. We also note that the tendency to link
      uncommon, nonobvious, percepts may not only be the basis of paranormal and
      paranoid ideas of reference, but also a prerequisite of creative thinking.

PMID- 11529424
TI  - Are children more accurate than adults? Spontaneous use of metaphor by children
      and adults.
AB  - This study examined an observation in which children outscored adults on a series
      of test questions, which included unusual items such as, "Do you see with your
      ears?" We assumed that the adults were treating the questions metaphorically
      because the literally correct answer was so obvious, an assumption consistent
      with Grice's theory. In Study 1, we tested this assumption by manipulating
      pretest and test items so as to suggest, or not suggest, a metaphorical or
      factual response. In Study 2, we used a similar manipulation involving the order
      of questions of various sorts and we more directly tested the Gricean hypothesis
      by giving college students a reason to treat the question literally. The results
      replicated the previous finding in which college students' scores were lower than
      those of children, and the condition effects suggested that the college students'
      performance was due to their responding metaphorically.

PMID- 11529425
TI  - Speech parts as Poisson processes.
AB  - This paper presents evidence that six of the seven parts of speech occur in
      written text as Poisson processes, simple or recurring. The six major parts are
      nouns, verbs, adjectives, adverbs, prepositions, and conjunctions, with the
      interjection occurring too infrequently to support a model. The data consist of
      more than the first 5000 words of works by four major authors coded to label the
      parts of speech, as well as periods (sentence terminators). Sentence length is
      measured via the period and found to be normally distributed with no stochastic
      model identified for its occurrence. The models for all six speech parts but the
      noun significantly distinguish some pairs of authors and likewise for the joint
      use of all words types. Any one author is significantly distinguished from any
      other by at least one word type and sentence length very significantly
      distinguishes each from all others. The variety of word type use, measured by
      Shannon entropy, builds to about 90% of its maximum possible value. The rate
      constants for nouns are close to the fractions of maximum entropy achieved. This
      finding together with the stochastic models and the relations among them suggest
      that the noun may be a primitive organizer of written text.

PMID- 11529426
TI  - Effects of NP type on the resolution of word-order ambiguities.
AB  - Locally ambiguous NP, NP2 V clauses in Dutch are preferably assigned a subject
      object rather than an object-subject interpretation, presumably on the basis of
      structurally based principles such as the Active-Filler Strategy. The present
      study investigates whether this preference can be affected by a
      nonconfigurational factor, namely the nature of NP2. The type of an NP
      (indefinite NPs, full definite NPs, pronouns) conveys information about the
      discourse status of the NP referent, which, in turn, is associated with a
      specific syntactic position. More specifically, pronouns are used to refer to
      given, salient entities in the discourse (topics); and NPs with such referents
      are generally encoded in subject position. A self-paced reading experiment shows
      that NP1 NP2 V relative clauses are preferably interpreted as subject-object when
      NP2 is a full definite NP (e.g., de vrouwen "the women"), but not when NP2 is the
      second person pronoun jullie ("you"-PL). This suggests that the structural bias
      for a subject-first order is not as strong as has been previously assumed, but is
      influenced by discourse information encoded in the NPs. Implications for parsing
      models are discussed.

PMID- 11529427
TI  - Mechanism and control of meiotic recombination initiation.
AB  - Homologous recombination is essential during meiosis in most sexually reproducing
      organisms. In budding yeast, and most likely in other organisms as well, meiotic
      recombination proceeds via the formation and repair of DNA double-strand breaks
      (DSBs). These breaks appear to be formed by the Spo11 protein, with assistance
      from a large number of other gene products, by a topoisomerase-like transesterase
      mechanism. Recent studies in fission yeast, multicellular fungi, flies, worms,
      plants, and mammals indicate that the role of Spo11 in meiotic recombination
      initiation is highly conserved. This chapter reviews the properties of Spo11 and
      the other gene products required for meiotic DSB formation in a number of
      organisms and discusses ways in which recombination initiation is coordinated
      with other events occurring in the meiotic cell.

PMID- 11529428
TI  - Cell-cell interactions in vascular development.
AB  - Research into areas as divergent as hemangiopoiesis and cardiogenesis as well as
      investigations of diseases such as cancer and diabetic retinopathy have converged
      to form the face of research in vascular development today. This convergence of
      disparate topics has resulted in rapid advances in many areas of vascular
      research. The focus of this review has been the role of cell-cell interactions in
      the development of the vascular system, but we have included discussions of
      pathology where the mechanism of disease progression may have parallels with
      developmental processes. A number of intriguing questions remain unanswered. For
      example, what triggers abnormal angiogenesis in the disease state? Are the
      mechanisms similar to those that control developmental neovascularization?
      Perhaps the difference in development in angiogenesis versus in disease is
      context driven, that is, an adult versus an embryonic organism. If this is the
      case, can the controls that curtail developmental vessel formation be applied in
      pathologies? Can cell-cell interactions be targeted as a control point for new
      vessel formation? For instance, can perivascular cells be stimulated or
      eliminated to result in increased vessel stability or instability, respectively?
      If the hypothesis that mural cell association is required for vessel
      stabilization is accurate, are there mechanisms to promote or inhibit mural cell
      recruitment and differentiation as needed? These and other questions lie in wait
      for the next generation of approaches to discern the mechanisms and the nature of
      the cell-cell interactions and the influence of the microenvironment on vascular
      development.

PMID- 11529429
TI  - Genetic regulation of preimplantation embryo survival.

PMID- 11529430
TI  - Osmoregulation and cell volume regulation in the preimplantation embryo.
AB  - The early preimplantation mammalian embryo possesses mechanisms that regulate
      intracellular osmolarity and cell volume. While transport of osmotically active
      inorganic ions might play a role in this process in embryos, the major mechanisms
      that have been identified and studied are those that employ organic osmolytes.
      Organic osmolytes provide a substantial portion of intracellular osmotic support
      in embryos and are required for their development under in vivo conditions. The
      main osmolytes that have been identified in cleavage stage embryos are
      accumulated via two transport systems of the neurotransmitter transporter family
      active in early preimplantation embryos--the glycine transport system (GLY) and
      the beta-amino acid transport system (system beta). While system beta has been
      established to have a similar role in many other cells, this is a novel function
      for the GLY transport system. The intracellular concentration of organic
      osmolytes such as glycine in early preimplantation embryos is regulated by
      tonicity, allowing the embryo to regulate its volume against shrinkage and to
      control its internal osmolarity. In addition, the cells of the embryo can
      regulate against an increase in volume via controlled release of osmolytes from
      the cytoplasm. This is mediated by a swelling-activated anion channel that is
      also highly permeable to a range of organic osmolytes, and which closely
      resembles similar channels found in many other cell types (VSOAC channels).
      Together, these mechanisms appear to regulate cell volume in the egg through the
      early cleavage stages of embryogenesis, after which there are indications that
      the mechanisms of osmoregulation change.

PMID- 11529431
TI  - Asthma and sex.

PMID- 11529432
TI  - A review of population studies from India to estimate national burden of chronic
      obstructive pulmonary disease and its association with smoking.
AB  - An attempt has been made to estimate the gross burden of chronic obstructive
      pulmonary disease (COPD) and its smoking association by reviewing the population
      studies available from India. Of the 14 studies which were reviewed, there were
      11 conducted in general populations. The median values of different prevalence
      rates (i.e. 5 percent in male and 2.7 percent in female population) were accepted
      as the most appropriate figures to calculate the overall estimates. The overall
      M:F ratio was 1.6:1, i.e. 61.6 percent males. The estimated total number of adult
      patients aged 30 years and above in 1996 were 8.15 million males and 4.21 million
      females. The smoker:non-smoker ratio in males was assessed at 82.3 percent with
      an estimated burden of 6.7 millions. When the prevalence rates of COPD and its
      smoking associations were assessed in three different time periods (before 1970;
      between 1971-1990; after 1990), the median rates of 1971-1990, when the maximum
      number of studies were conducted, were nearly the same as the overall rates.
      However, the total burden as well as the smoking associated COPD, increased with
      time due to an increase in the eligible base population. In conclusion, these
      figures can be used to estimate the burden of COPD and its smoking association in
      India for different statistical analyses.

PMID- 11529433
TI  - A prospective study of sensitivity and specificity of adenosine deaminase
      estimation in the diagnosis of tuberculosis pleural effusion.
AB  - We prospectively evaluated the usefulness of adenosine deaminase [ADA] estimation
      in the diagnosis of tuberculosis [TB] pleural effusion. Seventy five subjects
      with pleural effusion were studied. Forty eight of them had TB pleural effusion
      [M:F: 37:11; mean age 33 +/- 14.4 years range 17-76] and the remaining 27 had
      pleural effusion due to causes other than TB [non-TB group] [M:F: 19:8; mean age
      47.3 +/- 16.5 years; range 17-75]. Pleural fluid [PF] ADA levels were
      significantly higher in TB (n=48; mean 95.8 +/- 57.5 IU/L) compared with non-TB
      group (n=27; mean 30.7 +/- 27.2 IU/L) [p<0.001]. Serum ADA [S-ADA] levels were
      also significantly higher in TB (n=45; mean 39.6 +/- 18.3 IU/L) compared with non
      TB group (n=26; mean 18.0 +/- 13.7 IU/L) [p<0.001]. PF-ADA levels were higher
      compared to S-SDA in TB (p <0.001) and non-TB groups [p<0.01]. Using a cut off of
      35 IU/L, the sensitivity and specificity of PF-ADA in the diagnosis of TB was
      computed to be 83.3% and 66.6% respectively. At a cut-off level of 100 IU/L, PF
      ADA was found to have a sensitivity 40% and specificity 100%. From this study it
      is concluded that, using 100 IU/L as the cut-off, it is possible to avoid pleural
      biopsy to ascertain the diagnosis of TB in as much as 40% of the patients.

PMID- 11529434
TI  - Microbial pattern of acute infective exacerbation of chronic obstructive airway
      disease in a hospital based study.
AB  - Chronic bronchitis is associated with acute exacerbation, most often infective in
      origin. In order to study the bacteriological profile in such cases a total of 58
      patients were enrolled in this study from the chest clinic of our hospital. The
      male to female ratio was 2 to 1. Mean age of study group was 47 years. All
      patients had increased cough and sputum production. Barlett count, gram stain and
      sputum cultures were done for all patients. IgM and IgG antibodies for M.
      pneumoniae by ELISA were estimated in all cases. The etiological diagnosis could
      be established in 72% cases. S. pneumoniae (25.8%), P. aeruginosa (12%),
      Klebsiella sp (10.3%), B. catarrhalis (3.4%), S. aureus (1.7%) were isolated.
      Although M. pneumoniae was not cultured it was demonstrated serologically in 20%
      of cases. H. influenzae was not isolated in any case. The frequency of isolating
      an etiological agent increased with severity of dysponea.

PMID- 11529435
TI  - Morgagni hernia.

PMID- 11529436
TI  - Intrapleural streptokinase in a two-year-old child with a parapneumonic effusion.
AB  - A two-year-old child was hospitalised with features of parapneumonic effusion. He
      was initially managed with parenteral antibiotics and chest tube drainage. After
      three days drainage became insignificant inspite of chest tube being patent and
      appropriately positioned. CT scan of chest showed multiloculated effusion. In
      view of multiloculated effusion it was decided to try intrapleural fibrinolysis
      with streptokinase. Streptokinase in a dose of 1,25000 IU dissolved in 50 ml of
      normal saline was instilled through the chest tube daily. After instilling three
      doses, there was a significant increase in the drainage followed by almost
      complete radiological resolution. There were no side effects. Intrapleural
      streptokinase is a useful adjunctive threapeutic modality in the management of
      complicated parapneumonic effusion or empyema in paediatric patients.

PMID- 11529437
TI  - Pneumocystis carinii pneumonia in a patient with active untreated systemic lupus
      erythematosus.
AB  - Pneumonias due to Pneumocystis carinii (PCP) commonly occur in immunocompromised
      hosts. Although a treatable infection, it is associated with high mortality. A
      case of PCP presenting in an untreated case of systemic lupus erythematosus is
      reported, in view of the rarity of this association.

PMID- 11529438
TI  - Allergic bronchopulmonary aspergillosis with cavitary lesion simulating a lung
      abscess.
AB  - A 48-year-old female patient was diagnosed as a case of allergic bronchopulmonary
      aspergillosis (ABPA) on the basis of clinical, immunological and radiological
      criteria. In addition to central bronchiectasis, computed tomography (CT) of the
      thorax revealed hilar lymphadenopathy and cavitary lesions simulating a lung
      abscess, a presentation not described earlier. The patient responded to treatment
      with corticosteroids and the CT repeated after 14 months of treatment showed
      complete resolution of the cavitary lesions.

PMID- 11529439
TI  - Spontaneous resolution of diffuse alveolar septal amyloidosis.
AB  - Amyloidosis is a generic term for a heterogeneous group of disorders associated
      with deposition of protein in an abnormal fibrillar form. Amyloidosis can be
      hereditary or acquired, localised or systemic and potentially lethal or merely an
      incidental finding. We report a case of a male who was totally asymptomatic and
      was incidentally detected to have lung amyloidosis. He was not given any
      treatment but kept under observation., His chest radiograph (CXR) and high
      resolution computed tomograph (HRCT) of the chest cleared spontaneously after one
      year and the patient continues to remain asymptomatic even after two years.

PMID- 11529440
TI  - Field survey and literature review on traditional fermented milk products of
      Ethiopia.
AB  - The wide variety and the socio-economic and dietary importance of traditional
      fermented milk products of Ethiopia are discussed in this paper. Information on
      the microbiology of these products is sparse and has relevance to those organisms
      associated with spoilage and to those considered desirable for fermentation.
      There is a clear need to improve the production of African foods and beverages
      [Int. J. Food Microbiol. 18 (1993) 85]. The objective of this review was to
      document traditional technology used and information on the microbiology of the
      products, and to identify various constraints to the development and
      commercialisation of fermented milk products. Thereby the major problems and
      potential areas for improvement are pointed out. Ergo, the most important
      traditional product resembles yoghurt and, as the other traditional products, is
      prepared by "spontaneous" fermentation, commonly initiated by either "back
      slopping" or by repeated use of the same utensil. Other products include
      traditional fermented curd or ititu, traditional butter or kibe, neter kibe or
      traditional ghee, ayib resembling cottage cheese, arrera or defatted buttermilk
      and augat or traditional whey.

PMID- 11529441
TI  - Microstructural effects on microbial survival: phase-separating dextran
      solutions.
AB  - Evolving microstructure in a model dextran solution is shown to exert a major
      influence on the survival of Escherichia coli K-12 frag 1 and Salmonella
      typhimurium LT2. The microstructure results from microscopic phase separation,
      which develops over several hours resulting in hardening of the solution into a
      glassy state. The microstructure is characterized by an array of physical methods
      including image analysis, electron spin resonance and bulk rheology, and it is
      shown that bacterial survival depends on the formation of microscopic. water-rich
      domains and not primarily on bulk water activity or hardness.

PMID- 11529442
TI  - Hydrolysis of pork muscle sarcoplasmic proteins by Debaryomyces hansenii.
AB  - Strains of Debaryomyces hansenii originally isolated from sausages were screened
      for proteinase and aminopeptidase activity towards synthetic substrates. On the
      basis of these results, D. hansenii CT12487 was selected for further assays. The
      activities of the whole cells (WC), cell-free extracts (CFE) and a combination of
      both from the selected strain on pork muscle sarcoplasmic protein extracts were
      determined by protein, peptide and free amino acid analyses. There was a
      pronounced hydrolysis of protein bands of 110 kDa and 27-64 kDa regardless the
      incorporation of WC, CFE or a combination of both. The proteolytic activity also
      resulted in the generation of polar and non-polar peptides showing noticeable
      differences depending on the addition of WC or CFE. Whole cells generated greater
      amounts of free amino acids than the cell-free extracts.

PMID- 11529443
TI  - Efficacy of essential oils of Caesulia axillaris and Mentha arvensis against some
      storage pests causing biodeterioration of food commodities.
AB  - The essential oils of Caesulia axillaris and Mentha arvensis have been tested for
      their fumigant activity in the management of biodeterioration of stored wheat
      samples by Aspergillus flavus and the insect pests, Sitophilus oryzae and
      Tribolium castaneum, at 1300 and 600 ppm, respectively. The findings indicate the
      efficacy of the oils as potent fumigants for management of the biodeterioration
      of stored wheat samples. The oils also controlled the blue mould rot of oranges
      caused by Penicillium italicum and enhanced the market life of the oranges for a
      considerable period, showing their efficacy as postharvest fungicides of higher
      plant origin.

PMID- 11529444
TI  - Evidence for proteolytic activity and biogenic amines production in Lactobacillus
      curvatus and L. homohiochii.
AB  - After screening 372 strains of Lactobacillus spp. isolated from a Portuguese
      traditional dry fermented sausage, two Lactobacillus strains, a Lactobacillus
      homohiochii and a L. curvatus were selected, because they were positive for
      tyrosine and ornithine decarboxylase activities. Evidence for extracellular
      proteolytic activity was also demonstrated for the two Lactobacillus strains,
      with some strain variation in terms of specific activities towards different
      substrates. Proteolytic activity was shown to be maximal in the early exponential
      growth. This proteolytic activity was higher when cells were grown in a peptide
      rich medium such as MRS, when compared to skim milk. A study using several
      protease inhibitors showed that this activity is associated with metalloproteases
      in the case of the L. curvatus strain, but for L. homohiochii besides
      metalloproteases, serine-type proteases are also involved. In proteinaceous
      substrates, like dry fermented sausages, the formation of the biogenic amines
      putrescine and tyramine cannot be excluded when ongoing proteolysis leads to
      their precursors, as it is the case in the presence of these proteolytic
      Lactobacillus strains. Their ability to produce biogenic amines may be used as an
      index of microbial quality of the fermented meat product.

PMID- 11529446
TI  - A vision for psychiatric rehabilitation research.

PMID- 11529447
TI  - The Indiana Job Satisfaction Scale: job satisfaction in vocational rehabilitation
      for people with severe mental illness.
AB  - The Indiana Job Satisfaction Scale (IJSS) is a brief job satisfaction
      questionnaire designed for use with individuals with a severe mental illness.
      This study seeks to validate the IJSS, as well as to examine the relationship
      between job satisfaction and job tenure in a group of 71 workers in supported
      employment. Job satisfaction measured during the first 3 months of a job was
      significantly associated with job tenure; however, this relationship weakened
      over time. Overall, the findings support the utility of job satisfaction as a
      tool in vocational rehabilitation, as well as the validity of the IJSS with this
      group.

PMID- 11529445
TI  - An alternative approach for enumeration of Escherichia coli in foods.
AB  - An assay to screen Escherichia coli in foods using MUG supplemented lauryl
      sulfate tryptose (LST) broth instead of tryptone water (TW) medium was evaluated.
      The results presented in this paper suggest that this method is more sensitive
      for lower levels of E. coli, faster (16-18 h vs. 6-10 days) and less expensive
      (2.454 vs. 2.887 EURO/sample) than the standard ISO procedure. Thus, this method
      may be beneficial for use when both fecal coliforms and E. coli analyses are
      required in food systems.

PMID- 11529448
TI  - The state of knowledge of the effectiveness of consumer provided services.
AB  - There is a mixed record of research on consumer delivered services. There has
      been a great deal of descriptive work that supports the feasibility of consumer
      provided services. Only a limited number of studies have been reported that focus
      on outcomes for people who receive services from consumers. This new literature
      is at a critical juncture. This paper examines the state of research on three
      types of consumer provided services-consumer operated services, consumer
      partnership services, and consumers as employees. All these service types include
      consumers as paid providers who deliver mental health services to others, not
      primarily for their own benefit. This excludes self-help programs. Research
      resources need to be focused less on consumer provided services as adjunctive to
      professional services and more on determining the effectiveness of stand-alone
      consumer provided services in order to develop evidence to influence policy
      decisions.

PMID- 11529449
TI  - Reducing psychiatric hospital use of the rural poor through intensive
      transitional acute care.
AB  - A controlled study of the impact of brief, transitional acute care in reducing
      psychiatric treatment costs for people in rural areas is presented. Treatment
      emphasized home-based counseling and support, 24-hour rapid response, rural
      outreach, and intensive support management. The objective was to avert
      hospitalizations when possible, expedite discharge, and reduce likelihood of
      readmission, while maintaining comparable or superior clinical outcome. One
      hundred eighty-two participants were randomly assigned to the experimental group
      or a routine care control group. Clinical and utilization data tracked at initial
      contact, 2 weeks, 6 months, and 12 months suggest substantially lower hospital
      utilization for the experimental group. Clinical outcomes were comparable between
      groups.

PMID- 11529450
TI  - Predictors of psychosocial outcomes for patients with mood disorders: the effects
      of self-help group participation.
AB  - This study examined the predictors of psychosocial outcomes (daily functioning
      and management of illness) for people with mood disorders. After controlling for
      demographic, severity of illness, and social support predictor variables, the
      study evaluated whether participation in self-help groups would predict improved
      psychosocial outcomes. Post-hospitalization data were examined for 144 mood
      disorder patients using hierarchic multiple regression. More education predicted
      improved daily functioning; self-help involvement and education predicted
      management of illness. The implications of these findings for providing recovery
      oriented rehabilitation services are discussed.

PMID- 11529451
TI  - Getting ready for recovery: reconciling mandatory treatment with the recovery
      vision.
AB  - Considering treatment of serious mental illnesses, it might appear that the
      recovery model would be incompatible with any form of mandatory treatment. The
      authors suggest that this is not so. With individuals whose psychotic illness
      substantially impairs decision making, mandatory treatment may offer the best
      hope of getting well enough for recovery to be possible. It is essential,
      however, that any program involving involuntary community treatment involves
      recovering individuals who have themselves experienced a serious mental illness.
      The authors propose the use of a consumer-run guardianship program and a capacity
      review panel as two possible ways to achieve such participation.

PMID- 11529452
TI  - The IAPSRS toolkit: development, utility, and relation to other performance
      measurement systems. Members of the IAPSRS Research Committee. International
      Association of Psychological Rehabilitation Services.
AB  - The current climate of economic constraint in community-based mental health
      services has all but required psychosocial rehabilitation (PSR) programs to
      demonstrate their effectiveness by adopting outcome assessment systems. Agencies
      of disparate size and varying degrees of sophistication are now responding to
      mandates to systematically monitor program outcomes. In doing so, however, PSR
      practitioners and administrators are faced with a bewildering array of competing
      measures, some of which are impractical, costly, or irrelevant for capturing the
      outcomes of PSR services (Blankertz & Cook, 1998). To acquaint readers with
      issues in performance measurement in PSR, this article describes a newly
      developed outcome measurement system created to document the achievements of
      service recipients in PSR programs and to monitor progress towards recovery. We
      discuss principles and logistical issues in performance measurement which are
      important to PSR agencies and which the Toolkit has been designed to address.
      Results of the pilot testing of the PSR Toolkit are presented to demonstrate the
      feasibility of its use, logistical problems in implementation, psychometric
      properties of the measures, and the Toolkit's sensitivity to change. We discuss
      next steps in the development of the Toolkit.

PMID- 11529453
TI  - Predicting work outcomes and service use in supported employment services for
      persons with psychiatric disabilities.
AB  - New funding policies make it timely to identify correlates of effectiveness and
      effciency in supported employment (SE) programs for persons with psychiatric
      disabilities. In a statewide sample of SE participants with serious mental
      illness, individual clinical characteristics were unrelated to competitive work
      or hours of services consumed. However, amounts of SE provider time devoted to
      travel, training, and nonemployment advocacy were independently related to the
      likelihood of obtaining competitive work. These results suggest that SE providers
      should pursue an individualized, participant-driven model of services that
      includes active efforts to remove logistical barriers to community employment.

PMID- 11529454
TI  - Impact of an early psychosis program on substance use.
AB  - Approximately 37% of admissions to a recently developed program for first episode
      patients met criteria for substance abuse or dependence as well as criteria for
      one of the schizophrenia spectrum disorders. In this program the issue of
      substance use is addressed at the initial assessment and throughout the program.
      Several intervention strategies are integrated within the range of available
      psychosocial treatments. Additionally, we offer a specifically designed treatment
      strategy. This paper describes our 2-year experience with an integrated approach
      to reduce substance use in a specialized treatment program for individuals
      experiencing a first episode of psychosis.

PMID- 11529455
TI  - Informal community care for mental health consumers in Hong Kong.
AB  - Informal community care is crucial in community integration and rehabilitation of
      people with mental illness. In this paper, the writer describes the development
      of informal community care in Hong Kong. A self-help group, a relative group,
      integrative aftercare network, and the use of volunteers will be described and
      analyzed. However, these informal community care projects are underdeveloped.
      Participation is limited. Community integration is greatly hindered by public
      discrimination. The writer also suggests ways to develop the informal community
      care projects in Hong Kong.

PMID- 11529456
TI  - Rehabilitation for people with psychiatric disabilities: from care-role to
      payroll.
AB  - One of the most pressing problems faced by people recovering from psychiatric
      disabilities at Singapore Anglican Welfare Council (SAWC) continues to be
      difficulty in finding jobs. It is posited that recognized certification in
      various practical, marketable, vocational skills increases employment
      opportunities for people with psychiatric disabilities. In an effort to provide
      more effective training and to enhance integration, SAWC started two innovative
      in-house training programs: the On-tbe-Job Training (OJT) program and the
      Certificate in Office Skills (COS), both programs approved by the Singapore
      Institute of Technical Education (ITE). It has been found that people, after
      completion of the OJT; work with greater confidence and their work quality levels
      also increase. The COS started in September 1999 and will be completed in
      November 2000; however, people who participated in the course have responded with
      great enthusiasm because they were able to focus on a more definite goal in their
      future.

PMID- 11529457
TI  - Findings and recommendations from the IAPSRS Conference (2000) technology survey.
      International Association of Psychosocial Rehabilitation Services.

PMID- 11529458
TI  - Self-help visions and practices in Germany.
AB  - In this article the visions, possibilities and limits of self-help in Germany are
      discussed and the differences in diagnosis and the modalities of help between the
      professional culture and a self-help group ("Nachtschwarmer") are shown on the
      background of cultural transformations and changes within the psychiatric system.

PMID- 11529459
TI  - Slip sliding away: a journey from professional to consumer.
AB  - Although I am primarily known in my local mental health community for my
      professional advocacy and consumer satisfaction work, my consumer status has
      never been a secret. This article briefly details what has happened as I see and
      feel the effectiveness of my medications decrease along with my professional
      credibility and self-respect. Despite my diligence to my mental health and
      recovery practices, I, nonetheless, feel I am decompensating. The article
      explores some thoughts and lessons I am learning, along with my fellow
      consumers/professionals, as I find myself straddling the fence between these two
      groups of my colleagues.

PMID- 11529460
TI  - Risk and uncertainty: the unknown and psychiatric rehabilitation.

PMID- 11529461
TI  - Association of the 3467C>T mutation (T1156M) in the von Willebrand's factor gene
      with dominant type 1 von Willebrand's disease.
AB  - Type 1 is the most frequent form of von Willebrand's disease, which is
      characterized by a quantitative partial deficiency of von Willebrand's factor. At
      present, only two mutations located in the D3 domain (C1149R, C1130F) have been
      reported to cause the classic type 1 variant. The 3467C>T transition that
      predicts the T1156M amino acid change was detected in seven patients from one
      family and was not found in 110 normal alleles screened. This is a candidate
      mutation to cause dominant type 1 variant with complete penetrance. On the other
      hand, neither of the two mutations mentioned above has been detected in the other
      15 families studied with type 1 or possible type 1 patients.

PMID- 11529462
TI  - Clinicopathologic and prognostic features of chronic idiopathic thrombocytopenic
      purpura in adult Chinese patients: an analysis of 220 cases.
AB  - To determine the clinicopathologic and prognostic features of chronic idiopathic
      thrombocytopenic purpura (ITP) in adult Chinese patients, we conducted a
      retrospective analysis of 220 patients seen at a single center over a 40-year
      period. The female-to-male ratio was 4:1, with a mean age of 42.1 +/- 1.3 years,
      a mean platelet count of 33.7 +/- 2.3x10(9)/l, and a mean follow-up of 116 +/- 7
      months. Initial steroid treatment was required in 142 patients, 67 of whom
      (47.2%) achieved complete remission (CR). At 470 months, 46% patients remained in
      CR. Splenectomy was performed in 37 patients: in 23 patients due to primary
      steroid refractoriness and in 7 patients due to disease relapse following initial
      CR with steroids. In seven patients, data on response to steroids prior to
      splenectomy were not available. Splenectomy for steroid nonresponders resulted in
      an inferior CR rate (13 of 23, 56%) as compared with that for relapses after
      steroid treatment (7 of 7, 100%) (P<0.05). Compared with patients with negative
      antinuclear antibody (ANA), those who were ANA positive had similar responses to
      steroids, but significantly shorter remission after splenectomy (P<0.01). In
      conclusion, Chinese patients with ITP could maintain long-term remission after
      steroid therapy and splenectomy. In addition, primary steroid refractoriness and
      positive ANA were bad prognostic factors of the subsequent response to
      splenectomy.

PMID- 11529463
TI  - Very late antigen-5 and leukocyte function-associated antigen-1 are critical for
      early stage hematopoietic progenitor cell homing.
AB  - Interactions of adhesion molecules among hematopoietic progenitor cells (HPC),
      bone marrow microvascular endothelial cells (BMMEC), and stromal cells are
      critical for hematopoiesis. However, most of the identified HPC receptors mediate
      interactions between HPC and stromal cells in the extravascular space. In order
      to study the interaction between HPC and BMMEC in the early period of homing, we
      preincubated mouse bone marrow mononuclear cells with blocking monoclonal
      antibodies against very late antigen-4 (VLA-4), VLA-5, leukocyte function
      associated antigen-1 (LFA-1), and L-selectin before transplantation into
      irradiated splenectomized mice. Colony-forming units of granulocyte-macrophage
      (CFU-GM) seeding efficiency after preincubation with anti-VLA-5 resulted in a
      54%, 67%, and 65% reduction, while that after preincubation with anti-LFA-1
      resulted in a 37%, 25%, and 56% reduction, as compared with control, at 0.5, 2,
      and 24 h following transplantation, respectively. Similarly, the seeding
      efficiency was reduced by 12%, 13%, and 71% after preincubation with anti-VLA-4,
      and by -1%, 0%, and 18% after preincubation with anti-L-selectin. Thus, antibody
      blockade of VLA-5 and LFA-1 on HPC caused a significant decrease in CFU-GM
      seeding efficiency in the early period of homing. These observations suggest that
      VLA-5 and LFA-1 may play an important role in the recognition of BMMEC by HPC.

PMID- 11529464
TI  - Technetium-99m-sestamibi scintigraphy: an alternative approach for diagnosis and
      follow-up of active myeloma lesions after high-dose chemotherapy and autologous
      stem cell transplantation.
AB  - Technetium-99m-sestamibi (MIBI) is a radionuclide tracer taken up by different
      malignant tumors. A total of 88 MIBI scans were carried out in 20 individuals
      with monoclonal gammopathy of unknown significance (MGUS) and 10 patients during
      follow-up for other cancers. Of these 58 MIBI scans were carried out in 46
      myeloma patients: 15 at diagnosis, 14 during conventional chemotherapy, and 29
      following high-dose sequential therapy and autologous peripheral blood progenitor
      support. A positive MIBI scan was exhibited by lof 10 with non-myeloma cancers
      and 2 of 20 with MGUS. In contrast, all stage II and III multiple myelomas (MM)
      were positive at diagnosis. Therefore, the sensitivity of the MIBI scan at
      diagnosis was 100%, whereas the specificity in this cohort was 93%. Four
      different MIBI patterns could be distinguished in MM patients: physiological,
      focal, diffuse, and extramedullary uptakes. In comparison to conventional
      skeletal radiographs, MIBI scans recognized a higher number of myeloma lesions at
      diagnosis. MIBI scans remained positive in all patients during conventional
      chemotherapy, and there was a direct correlation between MIBI result and clinical
      outcome of patients following high-dose therapy. Eighteen patients had a negative
      MIBI scan: 9 were in complete remission (CR), 8 in partial remission (PR), and 1
      had progressive disease. Eleven patients showed lesions on the MIBI scan: 4 were
      in PR, 5 had progressive disease, 1 had a minimal response, and only 1 was in CR.
      A diffuse MIBI pattern reflected a higher bone marrow plasma cell number. In five
      patients, histologically or cytologically verified soft tissue myeloma lesions
      were correctly diagnosed by MIBI scan, while all plain radiographs showed none of
      them. MIBI has proven to be an effective tool in diagnosing biologically active
      myeloma.

PMID- 11529465
TI  - Autologous stem cell transplantation for follicular lymphoma: no benefit for
      early transplant?
AB  - Autologous stem cell transplantation (SCT) is widely used as salvage treatment
      for patients with relapsed follicular lymphoma (FL). Although SCT can induce
      prolonged remissions, it does not appear to be curative in the vast majority of
      patients. The purpose of this study was to investigate if incorporation of SCT
      into first-line therapy can improve its efficacy. Fifty-five patients underwent
      sequential high-dose therapy as up-front (n=33) or salvage treatment (n=22) for
      advanced stage FL at our institution. Treatment consisted of intensive
      chemotherapy with dexamethasone, carmustine (BCNU), etoposide, cytarabine, and
      melphalan (Dexa-BEAM) for mobilization of peripheral stem cells and reduction of
      tumor load, followed by one of three different myeloablative regimens and SCT.
      With a median follow-up of 4 years, projected event-free survival (EFS) and
      overall survival (OS) at 4 years post transplant was 59% and 84%, respectively,
      with no evidence of plateau in the survival curves. By univariate and
      multivariate analysis weighing age, sex, stage, BM and extranodal involvement,
      timing of transplant, ex vivo purging, and conditioning regimen [total body
      irradiation (TBI) vs non-TBI], the only significant factor predicting for
      superior EFS and OS was up-front vs salvage transplant (4-year EFS 76% vs 38%,
      p=0.02; 4-year OS 92% vs 73%, p=0.033). However, when calculated from diagnosis,
      EFS and OS of the up-front and salvage groups were virtually identical, implying
      that the longer survival post SCT in the up-front group was completely
      compensated by the longer interval between diagnosis and transplant in the
      salvage group. Median OS from diagnosis was 13.5 years. Except for one case of
      anaplastic large cell lymphoma, secondary neoplasms have not occurred to date. In
      conclusion, our data indicate that SCT might improve the prognosis of patients
      with disseminated FL, although it is probably not curative even if applied early
      during the course of the disease. The optimum timing of SCT remains to be
      determined by the ongoing randomized multicenter trial of the German Low-grade
      Lymphoma Study Group. The impact of radiotherapy on the success of SCT does not
      seem to be as essential as originally believed.

PMID- 11529466
TI  - The effect of optimal treatment on elderly patients with aggressive non-Hodgkin's
      lymphoma: more patients treated with unaffected response rates.
AB  - A substantial part of elderly patients (with good performance) with intermediate
      or high-grade non-Hodgkin's lymphoma (NHL) are not treated with the standard
      chemotherapy of cyclophosphamide, doxorubicin, vincristine, and prednisone
      (CHOP). If NHL patients are not treated with CHOP, the outcome is inferior. By
      adding granulocyte colony-stimulating factor (G-CSF) to CHOP chemotherapy, we
      aimed at treating more patients with less toxicity. We performed a multicenter
      population-based study (in the southeast of the Netherlands) in which elderly
      patients (> or = 60 years) with intermediate or high-grade stage > or = IIB NHL
      were treated with CHOP chemotherapy and growth factor G-CSF to increase the
      number of patients treated according to standard protocols. We also evaluated
      elderly NHL patients who were not treated with CHOP chemotherapy. Adequate
      therapy was defined as > or = six cycles or a total of five cycles when complete
      remission was achieved after three cycles. Seventy-nine NHL patients fulfilled
      the selection criteria. The patients were treated with CHOP plus G-CSF (n=46),
      CHOP (n=19), cyclophosphamide, vincristine, and prednisone (COP) (n=2),
      chlorambucil and prednisone (n=2), or prednisone (n=1). Nine patients were not
      treated with chemotherapy. The median age was 72 years (60-87). Of the 79 NHL
      patients, 65 were treated with CHOP chemotherapy (82%); 38 of 65 patients (59%)
      were adequately treated. The complete remission rate in the NHL group treated
      with CHOP was 65% (42 of 65 patients). The overall 3-year survival was 50%. Most
      of the patients died from progressive NHL (53% in the CHOP and 77% in the group
      not treated with CHOP). The treatment-related mortality was 15% in the CHOP
      group. The most important reason for not treating patients with CHOP (with or
      without G-CSF) was poor performance (WHO > or = 2). A significant subset of
      patients can be treated with CHOP chemotherapy with acceptable toxicity. The
      combination of CHOP plus G-CSF increased the absolute number of treatable elderly
      patients, resulting in more (absolute) patients with complete remission and
      overall survival compared to our previous study.

PMID- 11529467
TI  - Combination therapy with irinotecan (CPT-11), mitoxantrone, and dexamethasone in
      relapsed or refractory non-Hodgkin's lymphoma: a pilot study.
AB  - Irinotecan hydrochloride (CPT-11) is a topoisomerase I inhibitor with a broad
      antitumor spectrum. In the present study, we combined CPT-1 and mitoxantrone
      (MIT) with dexamethasone because the effect elicited by this combination was
      additive or better in a preclinical study. This study was performed to determine
      the efficacy and toxicities of this combination. Thirty-two patients were
      evaluable. CPT-11 combined with MIT achieved a complete remission in 11 patients
      (34.4%) and a partial remission in 9 patients (28.1%). The median follow-up
      period was 20 months. The 4-year survival rate was 31.8% (95% confidence
      intervals: 11.2-64.6%), and the 3-year event-free survival rate was 16.1% (95%
      confidence intervals: 8.2-24.6%). Grade 3 or higher hematological toxicity
      included neutropenia in 96.9%, anemia in 3.1%, and thrombocytopenia in 15.6%.
      Grades 1, 2, and 3 nonhematological toxicity included diarrhea in one patient,
      nausea/vomiting in five patients, and hematuria in one patient, respectively. CPT
      11 combined with MIT was safe even for elderly patients and was effective even in
      patients who had received pretreatment with doxorubicin. In addition, this
      regimen can be used on an outpatient basis. This combination should be tested
      further to determine the optimum doses and administration schedule.

PMID- 11529468
TI  - Treatment with all-trans retinoic acid in acute promyelocytic leukemia reduces
      early deaths in children.
AB  - All-trans retinoic acid (ATRA) is a known inducer of differentiation in acute
      promyelocytic leukemia. To improve the outcome of children with acute
      promyelocytic leukemia, ATRA has been applied since 1994 as an additional
      induction element inthe AML-BFM 93 study. In a retrospective study, we compared
      22 children treated with ATRA (median age: 9.3 years; range: 1.8-16.3) with 22
      patients receiving conventional therapy (median age: 12.3 years; range: 3.2
      16.7). Twenty-one of the children achieved complete remission. Only one patient
      died early from bleeding complications after 3 days administration of ATRA. In
      the control group, seven early deaths occurred (Fisher exact test; p<0.04). Two
      children died from intracerebral hemorrhages. Two patients suffered from sepsis
      during aplasia after induction therapy, and one child did not respond to
      treatment. The 5-year overall survival (OS) and event-free survival (EFS) of the
      children who received ATRA followed by chemotherapy were significantly bettercom
      pared with conventionally treated children [OS: 0.87 +/- 0.9 vs 0.45 +/- 0.11, p
      (log rank) <0.003; EFS: 0.76 +/- 0.11 vs 0.43 +/- 0.11 p (log rank) <0.02]; the
      median observation time was 2.8 years (19-76 months). However, nearly all
      children suffered from common side effects such as headache, fever, joint, muscle
      and bone pain, weight gain, or dermatitis. In three patients, a retinoic acid
      syndrome was observed. Interruption of ATRA treatment and application of
      dexamethasone, necessary in 12 children, controlled theadverse effects. ATRA
      treatment could be resumed in 18 patients. In conclusion, ATRA treatment during
      induction could avoid early deaths in children with acute promyelocytic leukemia
      with considerable but manageable toxic side effects.

PMID- 11529469
TI  - Spontaneous remission in a secondary acute myelogenous leukaemia following
      invasive pulmonary aspergillosis.
AB  - Spontaneous remission of adult acute myelogenous leukaemia (AML) represents a
      rare event. We report a 60-year-old female patient suffering from secondary AML
      M1 and severe invasive pulmonary hyalohyphomycosis highly suggestive of
      aspergillosis. Two months after the diagnosis of leukaemia, she achieved a
      spontaneous remission lasting 3 months, although neither cytostatic drugs nor
      corticoids were administered because of a septic condition. At the time of
      remission, a chronic hepatitis C virus infection and a polyclonal
      hypergammaglobulinaemia were present, and the patient received granulocyte colony
      stimulating factor once. This report represents the first documentation of a
      spontaneous remission in AML following invasive pulmonary hyalohyphomycosis.
      Possible mechanisms of this phenomenon are discussed.

PMID- 11529470
TI  - Bone resorption associated with uncoupling of osteoclastic and osteoblastic
      activities in adult T cell leukemia with hypercalcemia: case report.
AB  - A 64-year-old woman with adult T cell leukemia (ATL) was admitted to our hospital
      with severe hypercalcemia. The serum calcium level was elevated to 14.9 mg/dl.
      Biochemical parameters for bone formation including serum osteocalcin (bone Gla
      protein, BGP) and alkaline phosphatase (ALP) were normal. The serum levels of
      tartrate-resistant acid phosphatase (TRAP), a parameter for bone resorption, were
      increased (4.6 KAU). The serum level of parathyroid hormone-related protein
      (PTHrP) was elevated (343 pmol/l). The cytokines with stimulatory effects on bone
      resorption, such as interleukin (IL)-1alpha, IL-1beta, IL-6, and tumor necrosis
      factor-alpha, were not detected. Serum Ca levels, PTHrP levels, and TRAP levels
      decreased with the decrease in ATL cells after chemotherapy, while serum BGP
      levels and ALP levels increased. On the 29th hospital day, ATL cells began to
      increase again. Then serum PTHrP levels, Ca levels, and TRAP levels increased,
      while serum BGP levels and ALP levels decreased. A marked excessive bone
      resorption with suppressed bone formation (uncoupling) occurred in this patient.
      The ATL cells produced not only PTHrP but also IL-1alpha and IL-1beta. These
      results suggest that PTHrP may act as a humoral factor and IL-1 may act as a
      local factor in bone metabolism of ATL patients.

PMID- 11529472
TI  - Perioperative management of a patient with Fechtner syndrome.
AB  - Fechtner syndrome is a rare type of familial thrombocytopenia associated with
      large platelets, leukocyte inclusions, and features of Alport's syndrome. The
      bleeding tendency is usually mild, but severe hemorrhages have been reported.
      This is the case of a patient with Fechtner syndrome who was scheduled to undergo
      tonsillectomy. The patient had a history of easy bruising in childhood and a
      markedly prolonged bleeding time. Administration of DDAVP led to normalization of
      the bleeding time, and the patient underwent surgery without complications. With
      this approach the use of platelet concentrates could be avoided.

PMID- 11529471
TI  - Spontaneous pneumomediastinum and subcutaneous emphysema complicating
      bronchiolitis obliterans after allogeneic bone marrow transplantation--case
      report and review of literature.
AB  - Chronic graft-versus-host disease occurring in the setting of allogeneic bone
      marrow transplantation (BMT) can affect many organ systems, is a cause of
      significant morbidity, and contributes to late deaths. Bronchiolitis obliterans
      is a form of obstructive airway disease; when seen in the post-BMT setting, it is
      considered a manifestation of chronic graft-versus-host disease. Air-leak
      syndromes including pneumothoraces, pneumomediastinum and subcutaneous emphysema
      are rare complications of bronchiolitis obliterans. Here we describe a patient
      who developed pneumomediastinum, pneumopericardium, subcutaneous emphysema and
      pneumothorax secondary to severe bronchiolitis obliterans complicating the post
      bone marrow transplantation course.

PMID- 11529473
TI  - Fatal acute diclofenac-induced immune hemolytic anemia.
AB  - We report the case of a 72-year-old woman who developed fatal immune hemolytic
      anemia with multisystem organ failure and shock caused by diclofenac-dependent
      red blood cell autoantibodies. The patient described dramatically illustrates the
      potential severity of this adverse reaction and emphasizes the need for increased
      awareness of this complication of drug therapy.

PMID- 11529474
TI  - Phagocytosis decreases the density of IgG-Fc receptor III on neutrophils.

PMID- 11529475
TI  - "Allohormones": a class of bioactive substances favoured by sexual selection.
AB  - During close bodily contact, many species transfer substances that influence the
      behaviour or physiology of conspecifics. Such transfer is especially common
      during courtship and copulation. When this is the case the involved bioactive
      substances are favoured by sexual selection because their effects include
      increased egg production, inhibited remating, and changed sperm transport or
      storage in the partner. The direct mode of action of these substances is
      fundamentally different from that of pheromones and nuptial gifts. Therefore, the
      term allohormone is introduced here. An allohormone is defined as a substance
      that is transferred from one individual to another free-living member of the same
      species and that induces a direct behavioural or physiological response,
      bypassing external sensory organs. Although we emphasise the importance of
      allohormones in reproductive processes, allohormones may also have important
      functions outside of copulation.

PMID- 11529476
TI  - Social dominance, task performance and nutrition: implications for reproduction
      in eusocial wasps.
AB  - Dominance status is associated with individual differences in reproductive
      capacity in many animal societies, but the mechanisms that link social dominance
      to reproductive physiology are poorly understood. We propose a model for social
      dynamics that incorporates the nutritional costs and benefits of behavior:
      dominant individuals avoid energy-expensive behavior and build their nutritional
      reserves, thereby increasing their potential for reproduction. Greater
      reproductive capacity, once achieved, favors increased social dominance. To test
      the model, we measured relationships of females' nutrient storage and
      reproductive capacities with dominance status and task performance in the
      eusocial wasp Mischocyttarus mastigophorus. Ovary development was positively
      related with high levels of nutrient storage and with high rates of dominance
      behavior, but was not correlated with task performance. In contrast, high levels
      of nutrient storage were positively related with the performance of nutrient
      garnering and conserving tasks, but not with dominance behavior. These data
      support a model which places the nutritional costs of task performance as an
      intermediate causal link that connects dominance status with the accumulation of
      nutrient stores. Nutrient flow may be a general causal mechanism linking
      dominance status to reproductive capacity in animal societies.

PMID- 11529477
TI  - Sound transmission in the nose of the sperm whale Physeter catodon. A post mortem
      study.
AB  - During a sperm whale stranding at Romo, the Wadden Sea, Denmark, on 4 December
      1997, we were notified in time to start acoustic transmission measurements in the
      spermaceti complex 1 h after the specimen was seen alive. Frequency-modulated
      sound pulses, sweeping from 30 kHz to 10 kHz in 25 ms, were injected at the
      frontal surface at two positions: at the distal sac, and at the center of the
      junk (a compartmentalized structure below the spermaceti organ). A hydrophone
      next to the projector served as receiver. The analyses of the recordings show a
      repetitive, decaying reflection pattern at both projection sites, reminiscent of
      the multi-pulse click peculiar to sperm whales, although with minor differences
      in the duration of the intra-click intervals. This experimental evidence supports
      the Norris and Harvey (1972) theory of click generation in the spermaceti organ.
      Accordingly, the click is composed of a primary event, followed by a train of
      reflected pulses, spaced by the time required for the event to travel back and
      forth between air sacs (reflectors) at each end of the organ. The results also
      show that the junk readily transmits sound and probably is in acoustic contact
      with the spermaceti organ.

PMID- 11529478
TI  - Song production in auditory mutants of Drosophila: the role of sensory feedback.
AB  - To test the role of sensory feedback in song production. we analyzed the
      courtship songs of Drosophila males expressing auditory mutations. We compared
      the courtship songs of atonal (ato), beethoven (btv) and touch-insensitive-larva
      B (tilB) to wild-type songs. These mutations have in common the fact that the
      chordotonal organs are disrupted. Since chordotonal organs subserve both hearing
      (in the antenna) and proprioception (from the wing), these two potential routes
      for sensory feedback are defective in the mutant flies. We measured six song
      characters: pulse number within a train, inter-pulse interval, pulse duration,
      sine burst duration, the carrier frequency of the sine song and the relative
      amplitude of the sine song. Using multivariate analysis, we found significant
      differences between mutant and normal songs. In addition many mutant flies
      exhibit an unusual wing position during singing. The results indicate that
      sensory feedback plays an important role in shaping the courtship song of
      Drosophila.

PMID- 11529479
TI  - Red pigment-concentrating hormone induces a calcium-mediated retraction of distal
      retinal pigments in the crayfish.
AB  - The octapeptide red pigment-concentrating hormone is capable of eliciting the
      aggregation of intracellular pigment granules in distal retinal pigment cells of
      isolated retinas of the crayfish Procambarus clarkii (Girard). The final level
      and the time course of pigment aggregation are dose dependent within a range of
      10(-10) mol l(-1) to 10(-4) mol l(-1). The effect of red pigment-concentrating
      hormone is prevented by previous incubation with an anti- red pigment
      concentrating hormone antibody; however, application of the antibody after the
      onset of the red pigment-concentrating hormone effect, does not prevent its full
      development. A similar effect to that elicited by red pigment-concentrating
      hormone is induced by the calcium ionophores ionomycin and A-23187. Red pigment
      concentrating hormone evokes entry of 45Ca2+ to retinal cells. However, the red
      pigment-concentrating hormone-induced pigment aggregation persists in the
      presence of the calcium channel blocker verapamil and in Ca2+-free solutions.
      Caffeine and thapsigargin, known to release calcium from intracellular stores,
      elicit distal pigment aggregation, while ryanodine and dantrolene, blockers of
      intracellular calcium release, as well as the intracellular calcium chelator
      bapta-AM suppress the effect of red pigment-concentrating hormone. These results
      suggest that red pigment-concentrating hormone elicits distal retinal pigment
      aggregation by increasing intracellular calcium concentration, acting via a dual
      mechanism: (1) promoting calcium entry, and (2) releasing intracellular calcium.

PMID- 11529480
TI  - Mutations affecting the cAMP transduction pathway modify olfaction in Drosophila.
AB  - The rutabaga and dunce genes, encode two enzymes of the cyclic adenosine
      monophosphate transduction pathway in Drosophila, adenylyl cyclase and cyclic
      adenosine monophosphate phosphodiesterase, respectively. Two main second
      messenger systems, depending on inositol 1,4,5-triphosphate and cyclic adenosine
      monophosphate, have been associated with olfaction in vertebrates as well as
      invertebrates. A relationship between the cyclic adenosine monophosphate
      signaling pathway and olfactory reception in Drosophila is suggested by the
      presence of cyclic nucleotide gated channels and cyclic-nucleotide modulated K+
      channels in the antennae, the main olfactory organs. In this report, molecular,
      electrophysiological and behavioral data support the role of cyclic adenosine
      monophosphate in olfactory function for this species. Expression of both genes in
      the antennae has been shown by messenger ribonucleic acid analysis. Changes in
      the electroantennogram kinetics have been observed specifically on the slope of
      the initial rising phase, as predicted for processes that affect cyclic adenosine
      monophosphate concentration. Olfactory behavior changes due to both mutations
      were coherent with a functional meaning of the reported electrophysiological
      phenotype in olfactory perception. Sensitivity level increases or decreases for
      the mutants compared to the control line depending on the odorant. These results
      are compatible with some olfactory coding at the reception level by differential
      activation of a dual transduction system involving the inositol 1,4,5
      triphosphate and cyclic adenosine monophosphate cascades.

PMID- 11529481
TI  - Movement and sound generation by the toadfish swimbladder.
AB  - Although sound-producing (sonic) muscles attached to fish swimbladders are the
      fastest known vertebrate muscles, the functional requirement for such extreme
      speed has never been addressed. We measured movement of the swimbladder caused by
      sonic muscle stimulation in the oyster toadfish Opsanus tau and related it to
      major features of the sound waveform. The movement pattern is complex and
      produces sound inefficiently because the sides and bottom of the bladder move in
      opposite in and out directions, and both movement and sound decay rapidly. Sound
      amplitude is related to speed of swimbladder movement, and slow movements do not
      produce perceptible sound. Peak sound amplitude overlaps fundamental frequencies
      of the male's mating call because of muscle mechanics and not the natural
      frequency of the bladder. These findings suggest that rapid muscle speed evolved
      to generate sound from an inefficient highly damped system.

PMID- 11529482
TI  - Coding of concurrent vocal signals by the auditory midbrain: effects of duration.
AB  - Neural selectivity to signal duration within the auditory midbrain has been
      observed in several species and is thought to play a role in signal recognition.
      Here we examine the effects of signal duration on the coding of individual and
      concurrent vocal signals in a teleost fish with exceptionally long duration
      vocalizations, the plainfin midshipman, Porichthys notatus. Nesting males produce
      long-duration, multi-harmonic signals known as hums to attract females to their
      nests; overlapping hums produce acoustic beats at the difference frequency of
      their spectral components. Our data show that all midbrain neurons have sustained
      responses to long-duration hum-like tones and beats. Overall spike counts
      increase linearly with signal duration, although spike rates decrease
      dramatically. Neurons show varying degrees of spike rate decline and hence,
      differential changes in spike rate across the neuron population may code signal
      duration. Spike synchronization to beat difference frequency progressively
      increases throughout long-duration beats such that significant difference
      frequency coding is maintained in most neurons. The significance level of
      difference frequency synchronization coding increases by an order of magnitude
      when integrated over the entirety of long-duration signals. Thus, spike
      synchronization remains a reliable difference frequency code and improves with
      integration over longer time spans.

PMID- 11529483
TI  - Anatomy and in vivo activity of neurons connecting the crustacean stomatogastric
      nervous system to the brain.
AB  - In decapod crustaceans, the inferior ventricular nerve connects the cerebral
      ganglia (brain) with the stomatogastric nervous system (STNS). In the ivn of the
      crayfish, eight axons with diameters between 3.5 microm and 10 microm were found
      in close proximity to the oesophageal ganglion. Two of these axons terminate with
      their cell body within the ivn. The projections of the other six axons spread
      inside many neuropiles of the brain, mainly within the protocerebrum and the
      neuropils of the first and second antennae. Several fibers also send neurites via
      the circumoesophageal connectives toward the paired commissural ganglia and
      further down to the ventral nerve cord. The activity of motoneurons within the
      STNS and of axons in the ivn was recorded with implanted electrodes before,
      during and after times of feeding. At the beginning of feeding all tonically
      active ivn neurons accelerated their discharge rate and initially silent neurons
      also started to fire. Spike frequency was correlated with the quantity of food
      consumed. The ivn response was accompanied by a corresponding increase in pyloric
      frequency and an initiation of a gastric rhythm. The two motor rhythms showed a
      strong phasic interaction, but there was no phase coupling to the ivn activity.

PMID- 11529484
TI  - Dynamic responses of tibial campaniform sensilla studied by substrate
      displacement in freely moving cockroaches.
AB  - Responses of the tibial campaniform sensilla, receptors that encode strains in
      the exoskeleton, were characterized by recording sensory activities during
      perturbations in freely standing cockroaches. The substrate upon which the animal
      stood was displaced horizontally using ramp and hold stimuli at varied rates. The
      sensilla showed short latency responses that were initiated in the first 30 ms of
      platform movement. Responses of individual receptors depended upon the direction
      of displacement and the orientation of their cuticular cap. Proximal receptors,
      whose caps are perpendicular to the long axis of the tibia, responded to
      displacements directed from the contralateral side of the body and from the head
      toward the abdomen. The distal sensilla, oriented parallel to the tibia,
      discharged at longer latency to displacements in opposite directions. Plots of
      receptor activity versus displacement direction showed that proximal and distal
      sensilla are activated in non-overlapping ranges of movement direction. Afferent
      responses also increased as the platform was displaced more rapidly. These
      results are consistent with a model in which displacements produce forces that
      result in bending of the tibia. This information could be utilized to detect the
      direction and rate of forces that occur during leg slipping or in walking on
      unstable terrains.

PMID- 11529485
TI  - The E. Donnall Thomas Lecture 2001. Improve the outcome of autologous
      hematopoietic cell transplantation!

PMID- 11529486
TI  - Intercellular adhesion molecule-I (ICAM-I, CD54) deficiency segregates the unique
      pathophysiological requirements for generating idiopathic pneumonia syndrome
      (IPS) versus graft-versus-host disease following allogeneic murine bone marrow
      transplantation.
AB  - Following allogeneic bone marrow transplantation (alloBMT), idiopathic pneumonia
      syndrome (IPS) and graft-versus-host disease (GVHD) caused by donor cell
      alloreactivity remain major obstacles to a successful outcome. Intercellular
      adhesion molecule-1 (ICAM-1) is an adhesion molecule that is involved in
      regulating lymphohematopoietic cell migration and facilitating T-cell responses.
      To determine whether ICAM-1 expression in the host would affect IPS or GVHD
      tissue injury responses, ICAM-1(-/-) mice were compared with ICAM-1(+/+)
      controls. ICAM-1(-/-) recipients did not exhibit the manifestations of IPS injury
      such as an increase in lung weights nor decreased lung function. The influx of T
      cells, macrophages, and neutrophils was dramatically dampened as was the
      production of the inflammatory cytokines interferon-gamma and tumor necrosis
      factor alpha and the chemokines monocyte chemotactic protein 1, macrophage
      inflammatory protein 1alpha (MIP-1alpha), MIP-1beta, and lymphotactin, normally
      upregulated in the lung during IPS. In contrast, systemic levels of these
      mediators were unaffected and GVHD-induced lesions in the liver and colon did not
      differ in severity regardless of ICAM-1 expression. GVHD-mediated mortality was
      accelerated in ICAM-1(-/-) recipients at doses of allogeneic spleen cells that
      are otherwise not uniformally lethal. These data implicate ICAM-1 as playing a
      critical role in the generation of IPS; therefore, ICAM-1 may be a discerning
      element, segregating IPS from GVHD injury post-alloBMT.

PMID- 11529487
TI  - Generation of HLA-C-specific cytotoxic T cells in association with marrow graft
      rejection: analysis of alloimmunity by T-cell cloning and testing of T-cell
      receptor rearrangements.
AB  - Peripheral blood mononuclear cells from a patient who rejected a T-cell-depleted
      marrow graft showed spontaneous cytotoxic activity specific for HLA-Cw4 and HLA
      B35 alloantigens of the donor. T-cell-receptor complementarity-determining region
      3 length distributions in a blood sample obtained at the time of rejection
      generally showed distortions in only 1 or 2 peaks, indicating that recipient T
      cells with a broad repertoire of antigen receptors survived the
      pretransplantation conditioning regimen. An HLA-Cw4-specific, CD8 T-cell clone
      was recovered from a blood sample after rejection. The T-cell-receptor-B gene
      rearrangement expressed by this clone was not readily detectable in other blood
      samples drawn before or after the transplantation, indicating that this clone was
      only 1 of many recipient-derived T cells that recognized HLA alloantigens of the
      donor. These results demonstrate the role of the HLA-C locus in T-cell-mediated
      alloimmune responses and add to emerging evidence that indicates the need to
      evaluate HLA-C compatibility in selecting hematopoietic stem cell donors for
      patients who have an increased risk of rejection.

PMID- 11529488
TI  - Association of TLR4 mutations and the risk for acute GVHD after HLA-matched
      sibling hematopoietic stem cell transplantation.
AB  - Lipopolysaccharide (LPS) has been implicated in the pathogenesis of graft-versus
      host disease (GVHD). The toll-like receptor (TLR)-4 has been recently identified
      as a major receptor for LPS. Mutations of TLR4 have been associated with LPS
      hyporesponsiveness. We hypothesized that TLR4 mutations reduce the risk of acute
      GVHD in allogeneic marrow transplant recipients. In a preliminary study to
      determine the frequency of TLR4 mutations and their possible association with
      GVHD, we tested 237 patients and their HLA-identical sibling donors for 2 TLR4
      polymorphisms. All patients received methotrexate and cyclosporine for GVHD
      prophylaxis. One or more mutants were detected in 10.8% of patients and 10.6% of
      donors. Multivariable logistic regression models were used to analyze the
      association between TLR4 mutations and probability (1-sided) of GVHD. The odds
      ratio (adjusted for advanced disease, total body irradiation dose, and patient
      age) for development of grades II to IV GVHD when a mutation was present in the
      recipient was 0.63 (95% confidence interval [CI], 0.25-1.60; P = .16). When a
      mutation was present in the donor, the adjusted odds ratio was 0.88 (95% CI, 0.36
      2.17; P = .40). When a mutation was present in both recipient and donor, the odds
      ratio was 0.72 (95% CI, 0.22-2.32; P = .29). Among 24 patients with TLR4
      mutations in either donor or recipient, 4 (16.7%) developed gram-negative
      bacteremia. Among 213 patients without mutations, 14 (6.6%) developed gram
      negative bacteremia (P = .09). The data indicate that a reduced risk of acute
      GVHD is associated with TLR4 mutations and that TLR4 mutations may increase the
      risk for gram-negative bacteremia. However, these associations are not
      statistically significant in recipients of HLA-matched sibling marrow transplants
      who are prophylactically treated for infections and GVHD. A much larger study
      population would be needed to confirm the role of LPS in the pathogenesis of GVHD
      in humans.

PMID- 11529489
TI  - Adenoviral infections and a prospective trial of cidofovir in pediatric
      hematopoietic stem cell transplantation.
AB  - Adenoviral (ADV) infections are increasingly recognized as a cause of morbidity
      and mortality in pediatric hematopoietic stem cell transplantation (HSCT). We
      reviewed our experience with ADV infections in HSCT patients hospitalized for
      transplantation at Childrens Hospital Los Angeles January 1998 through December
      1998. ADV was detected in 47% of patients, with recipients of HSCT from
      alternative donors (matched unrelated, unrelated cord, and mismatched related
      donors) being more frequently culture positive than recipients of HSCT from
      matched siblings (62% versus 27%, P = .04). Detection of ADV from 2 or more sites
      was associated with organ injury, eg, hemorrhagic cystitis, enteritis, and
      hepatitis. Because of the high incidence of ADV culture-positive patients and the
      lack of effective anti-ADV therapy, we initiated a prospective trial to evaluate
      cidofovir (CDV) in the treatment of ADV infections in HSCT recipients. Eight
      patients were enrolled on a dosage schedule of 1 mg/kg 3 times weekly. AD of
      these patients eventually achieved long-term viral suppression and clinical
      improvement, although 6 patients needed prolonged CDV therapy for up to 8 months
      before CDV could be stopped without ADV recurrence. We did not observe dose
      limiting nephrotoxicity, and the discontinuation of the drug was not required in
      any patients. Prospective controlled trials to further define the role of CDV in
      the treatment of ADV infections in HSCT patients are warranted.

PMID- 11529490
TI  - Low incidence of Epstein-Barr virus-associated posttransplantation
      lymphoproliferative disorders in 272 unrelated-donor umbilical cord blood
      transplant recipients.
AB  - Umbilical cord blood (UCB) is being increasingly used for transplantation, but
      the ability of neonatal T cells to regulate Epstein-Barr virus (EBV)-associated
      lymphoproliferation is unknown. Because UCB transplantation (UCBT) is associated
      with a relatively low infused dose of donor T cells, frequent donor-recipient HLA
      disparity, and use of antithymocyte globulin during conditioning, we hypothesized
      that the risk of EBV-associated posttransplantation lymphoproliferative disorders
      (EVB-PTLD) after UCBT may be increased. To investigate the incidence of EBV-PTLD
      after UCBT, we analyzed 272 unrelated-donor UCBTs performed from August 1993 to
      December 1999 at Duke University Medical Center and the University of Minnesota.
      Five cases of EBV-PTLD were identified, with a cumulative incidence of 2% (95%
      confidence interval, 0.3%-3.7%) at 2 years. EBV-PTLD affected UCB recipients aged
      1 to 49 years (median, 8 years), with 4 patients undergoing transplantation for
      leukemia and 1 for immunodeficiency. Patients received UCB grafts that were HLA
      matched (n = 1) or mismatched at 1 (n = 1) or 2 (n = 3) HLA loci. Diagnoses
      occurred at 4 to 14 months (median, 6 months) after UCBT, with 4 of 5 patients
      having preceding grade II to IV acute graft-versus-host disease and 1 being
      diagnosed at autopsy. Treatment of 4 patients consisted of withdrawal of
      immunosuppressive treatment and administration of rituximab, with 2 of 4 patients
      responding. Thus, the incidence of EBV-PTLD after unrelated-donor UCBT appears
      similar to that observed after transplantation using unrelated bone marrow (BM)
      and compares favorably with unrelated-donor T-cell-depleted BM transplantation.
      Because adoptive immunotherapy with donor lymphocytes is not an available option
      for recipients of unrelated-donor UCBT, new therapeutic strategies are needed,
      and rituximab appears promising.

PMID- 11529491
TI  - ASBMT raises concerns about FDA draft rules for "good tissue practices".

PMID- 11529493
TI  - Neurotrophic factor structures reveal clues to evolution, binding, specificity,
      and receptor activation.
AB  - The neutrophin family, the glial-derived neurotrophic factor family, and the
      ciliary neurotrophic factor are the best described growth factors specific for
      developing neurons and neutral crest cells. As might be expected for regulatory
      molecules of the complex central and peripheral nervous system, these factors
      show considerable receptor specificity and cross-talk. Thanks to a decade of
      intense research by numerous laboratories, the structures of many of these
      factors are now available. This review discusses the structural bases of receptor
      binding, specificity, and activation in each of these systems. Using structure
      based sequence alignments, the evolutionary implications of these molecules and
      their receptors are discussed, followed by suggestions for further directions for
      research on the structure and function of these neurotrophic factors.

PMID- 11529494
TI  - Genes for neurotrophic factors and their receptors: structure and regulation.
AB  - Neurotrophins and their receptors have attracted much interest during the last
      two decades. Although the mode of action of molecules of the neurotrophin system
      has been studied extensively, information on molecular mechanisms governing their
      expression is mosaic and incomplete. This review attempts to summarize the data
      available on gene structure and transcriptional regulation of neurotrophins and
      their receptors, and outlines perspectives for the future in this field.

PMID- 11529495
TI  - Receptor binding, internalization, and retrograde transport of neurotrophic
      factors.
AB  - This review deals with the receptor interactions of neurotrophic factors,
      focusing on the neurotrophins of the nerve growth factor (NGF) family, the glial
      cell derived neurotrophic factor (GDNF) family, and the ciliary neurotrophic
      factor (CNTF) family. The finding that two proteins, p75NTR and Trk, act as
      receptors for NGF in neurons generated the discovery of other neurotrophic
      factors/receptor families and has enhanced our understanding of the development,
      survival, regeneration, and degeneration of the nervous system. The kinetics of
      binding, the structure of the ligand-receptor complex, and the mechanism of
      retrograde transport of the neurotrophins are discussed in detail and compared to
      information available on the GDNF and CNTF families. Each neurotrophic factor
      family, i.e., NGF, GDNF, and CNTF, has a set of receptors with specificity for
      individual members of the family and a common receptor without member specificity
      that, in some families, generates the cellular signal and retrograde transport.

PMID- 11529496
TI  - Local and target-derived actions of neurotrophins during peripheral nervous
      system development.
AB  - Neurotrophic factors are present in limiting quantities, and neurons that obtain
      an adequate supply of the required neurotrophic factor survive whereas those that
      compete unsuccessfully die. Analysis of null mutant mice for neurotrophins and
      Trk receptors as well as in vivo experiments in ovo in the chick applying
      exogenous neurotrophins or neutralising antisera have significantly increased
      knowledge of the roles they play during development. This review focuses on
      recent advances in understanding the various roles of neurotrophins in dorsal
      root ganglion sensory neuron development at different times in embryonic
      development--an early local role for differentiation of the sensory precursor
      cells and a later survival-promoting target-derived role for the mature neurons.

PMID- 11529497
TI  - Neurotrophin signalling pathways regulating neuronal apoptosis.
AB  - Recent evidence indicates that naturally occurring neuronal death in mammals is
      regulated by the interplay between receptor-mediated prosurvival and proapoptotic
      signals. The neurotrophins, a family of growth factors best known for their
      positive effects on neuronal biology, have now been shown to mediate both
      positive and negative survival signals, by signalling through the Trk and p75
      neurotrophin receptors, respectively. The mechanisms whereby these two
      neurotrophin receptors interact to determine neuronal survival have been
      difficult to decipher, largely because both can signal independently or
      coincidentally, depending upon the cell or developmental context. Nonetheless,
      the past several years have seen significant advances in our understanding of
      this receptor signalling system. In this review, we focus on the proapoptotic
      actions of the p75 neurotrophin receptor (p75NTR), and on the interplay between
      Trk and p75NTR that determines neuronal survival.

PMID- 11529498
TI  - Neurotrophins and neuronal differentiation in the central nervous system.
AB  - The central nervous system requires the proper formation of exquisitely precise
      circuits to function properly. These neuronal circuits are assembled during
      development by the formation of synaptic connections between hundreds of
      thousands of differentiating neurons. For these circuits to form correctly,
      neurons must elaborate precisely patterned axonal and dendritic arbors. Although
      the cellular and molecular mechanisms that guide neuronal differentiation and
      formation of connections remain mostly unknown, the neurotrophins have emerged
      recently as attractive candidates for regulating neuronal differentiation in the
      developing brain. The experiments reviewed here provide strong support for a
      bifunctional role for the neurotrophins in axonal and dendritic growth and are
      consistent with the exciting possibility that the neurotrophins might mediate
      activity-dependent synaptic plasticity.

PMID- 11529499
TI  - The neurotrophic factors in non-neuronal tissues.
AB  - Although neurotrophic factors are defined as molecules that maintain neuronal
      cells, they possess a range of functions outside the nervous system. For example,
      glial cell line-derived neurotrophic factor is essential for ureteric branching
      in kidney morphogenesis and for regulating the fate of stem cells during
      spermatogenesis. Leukemia inhibitory factor, a member of the interleukin-6 (IL-6)
      ciliary neurotrophic factor family, inhibits differentiation of embryonic stem
      cells, induces tubulogenesis in the embryonic kidney, and regulates sperm
      differentiation. Other IL-6 family members are important in cardiac
      differentiation and they have pleiotropic functions in the hematopoietic and
      immune systems. Although neurotrophin receptors have been found on a number of
      non-neuronal tissues, they represent mostly truncated receptor isoforms that are
      incapable of signal transduction and may have scavenger or dominant negative
      functions. However, several examples can be presented of essential non-neuronal
      functions played by neurotrophins in e.g., cardiac, hair follicle, and vascular
      differentiation, and the maintenance of immune cells.

PMID- 11529501
TI  - Congenital disorders involving defective N-glycosylation of proteins.
AB  - This review deals with several of the main autosomal recessive congenital
      disorders involving defective N-glycosylation of proteins (the addition of
      glycans linked to the polypeptide chain by a beta-linkage between the anomeric
      carbon of N-acetylglucosamine and the amido group of L-asparagine). These
      congenital disorders of glycosylation (CDG, previously known as carbohydrate
      deficient glycoprotein syndromes) are a group of multisystemic diseases often
      involving severe psychomotor retardation. Six distinct variants of CDG in group I
      (types Ia-If) have been described to date and the defects have been localized to
      deficiencies in the assembly of the dolichylpyrophosphate-linked oligosaccharide
      N-glycan precursor and its transfer to asparagine residues on the nascent
      polypeptides. Two variants of CDG group II (types IIa and IIb) have been
      identified as defects in the processing of protein-bound N-glycans. Hereditary
      erythroblastic multinuclearity with a positive acidified-serum lysis test
      (HEMPAS; congenital dyserythropoietic anemia type II) presents as a relatively
      mild dyserythropoietic anemia. The genetic defect in most cases of HEMPAS is not
      known, but alpha-3/6-mannosidase II is involved in at least some patients.
      Leukocyte adhesion deficiency type II (LAD II) is a rare disorder characterized
      by recurrent infections, persistent leukocytosis and severe mental and growth
      retardation. LAD II is due to lack of availability of GDP-fucose. The study of
      these diseases and of relevant animal models has provided strong evidence that N
      glycans are essential for normal mammalian development.

PMID- 11529502
TI  - Friedrich Miescher Prize awardee lecture review. A conserved family of nuclear
      export receptors mediates the exit of messenger RNA to the cytoplasm.
AB  - The distinguishing feature of eukaryotic cells is the segregation of RNA
      biogenesis and DNA replication in the nucleus, separate from the cytoplasmic
      machinery for protein synthesis. As a consequence, messenger RNAs (mRNAs) and all
      cytoplasmic RNAs from nuclear origin need to be transported from their site of
      synthesis in the nucleus to their final cytoplasmic destination. Nuclear export
      occurs through nuclear pore complexes (NPCs) and is mediated by saturable
      transport receptors, which shuttle between the nucleus and cytoplasm. The past
      years have seen great progress in the characterization of the mRNA export pathway
      and the identification of proteins involved in this process. A novel family of
      nuclear export receptors (the NXF family), distinct from the well-characterized
      family of importin beta-like proteins, has been implicated in the export of mRNA
      to the cytoplasm.

PMID- 11529500
TI  - Trans-Golgi network sorting.
AB  - The trans-Golgi network (TGN) is a major secretory pathway sorting station that
      directs newly synthesized proteins to different subcellular destinations. The TGN
      also receives extracellular materials and recycled molecules from endocytic
      compartments. In this review, we summarize recent progress on understanding TGN
      structure and the dynamics of trafficking to and from this compartment. Protein
      sorting into different transport vesicles requires specific interactions between
      sorting motifs on the cargo molecules and vesicle coat components that recognize
      these motifs. Current understanding of the various targeting signals and vesicle
      coat components that are involved in TGN sorting are discussed, as well as the
      molecules that participate in retrieval to this compartment in both yeast and
      mammalian cells. Besides proteins, lipids and lipid-modifying enzymes also
      participate actively in the formation of secretory vesicles. The possible
      mechanisms of action of these lipid hydrolases and lipid kinases are discussed.
      Finally, we summarize the fundamentally different apical and basolateral cell
      surface delivery mechanisms and the current facts and hypotheses on protein
      sorting from the TGN into the regulated secretory pathway in neuroendocrine
      cells.

PMID- 11529503
TI  - Opposite pattern of MDR1 and caveolin-1 gene expression in human atherosclerotic
      lesions and proliferating human smooth muscle cells.
AB  - Cholesterol esterification and smooth muscle cell (SMC) proliferation are the
      crucial events in the development of atherosclerotic lesions. The objective of
      this study was to analyse cholesterol esterification and the expression of MDR1
      (multidrug resistance), ACAT (acyl-CoA:cholesterol acyltransferase) and caveolin
      1 genes in atherosclerotic and healthy vascular walls, in SMCs obtained from
      atherosclerotic lesions and saphenous veins. Results demonstrated higher levels
      of cholesterol esters, ACAT and MDR1 mRNAs and lower levels of caveolin-1 mRNA in
      atherosclerotic segments compared to adjacent serial sections of the same artery
      and the corresponding non-atherosclerotic arteries from cadaveric donors. SMCs
      isolated from atherosclerotic plaques manifested an increased capacity to
      esterify cholesterol and to grow at a faster rate than SMCs isolated from
      saphenous veins. In addition, when SMCs from atherosclerotic plaques were
      cultured in the presence of progesterone, a potent inhibitor of cholesterol
      esterification, significant growth suppression was observed. An increase in ACAT
      and MDR1 expression and a concomitant decrease in caveolin-1 expression were also
      observed in SMCs isolated from atherosclerotic arteries as early as 12 h after
      serum stimulation. An opposite pattern was found when SMCs were treated with
      progesterone. These findings support the idea that cholesterol esterification
      plays a role both in early atherogenesis and in clinical progression of advanced
      lesions and raise the possibility that the cholesterol ester pathway might
      directly modulate the proliferation of SMCs.

PMID- 11529505
TI  - The ecdysteroid agonist/antagonist and brassinosteroid-like activities of
      synthetic brassinosteroid/ecdysteroid hybrid molecules.
AB  - A series of synthetic hybrid brassinosteroid/ecdysteroid structures has been
      assessed for their ecdysteroid agonist/antagonist activities in the Drosophila
      melanogaster B(II) cell bioassay and for brassinosteroid-like activity in the
      rice lamina inclination test. Most of the compounds proved inactive for
      ecdysteroid agonist activity, demonstrating the specificity of the ecdysteroid
      receptor for compounds closely structurally related to 20-hydroxyecdysone.
      However, compound 18, with 14alpha-hydroxy-7-en-6-one and 22S-hydroxy
      functionalities (as in most active ecdysteroids), possessed distinct agonist
      activity (median effective concentration = 1.4 x 10(-5) M), although this is
      still almost 2000-fold less active than 20-hydroxyecdysone (25). Compounds 13 and
      15 possessed weak agonist activity. Compounds 5, 11 and 14 weakly antagonised the
      action of 20-hydroxyecdysone (at 5 x 10(-8) M) on B(II) cells. In the
      brassinosteroid bioassay, most of the tested compounds showed activity. This may
      reflect the metabolic capability of plant tissue to convert test compounds to
      more active analogues. However, it is clear that biological activity declines as
      the structure of the test compound deviates further from that of castasterone
      (16). Three ecdysteroids (25, 26 and 27) are completely inactive in the rice
      lamina inclination test. These studies demonstrate the high specificities of the
      insect ecdysteroid receptor and the plant brassinosteroid receptor and indicate
      that phytoecdysteroids, even in high concentrations, would not interfere with
      brassinosteroid signalling pathways in plants where the two classes of compounds
      co-occur. Equally, brassinosteroids would not interfere with ecdysteroid
      signalling in insects, especially if one takes into account the low
      concentrations of brassinosteroids in the diet of phytophagous insects.

PMID- 11529504
TI  - On the distribution of phytoecdysteroids in plants.
AB  - The occurrence and levels of phytoecdysteroids in the seeds and other parts of
      plants grown from the seeds of 180 randomly selected plant species were assessed
      and compared. Ecdysteroids are frequently detectable in leaves and flowers, but
      less so in stems, roots and seeds. The seeds of 290 species were assessed for the
      presence of hydrolysable ecdysteroid conjugates. Low levels of conjugates were
      detected in a significant number of species, large amounts being present only
      when levels of free ecdysteroids were high. Individual plants of Arabidopsis
      thaliana were assessed for the presence of phytoecdysteroids. While plants of
      this species are generally ecdysteroid negative, individual plants in the
      population accumulate low levels of ecdysteroids. Extracts of seeds of 50
      "ecdysteroid-negative" species were concentrated and partially purified to
      determine if they possess ecdysteroids at levels below the usual detection
      levels. Ecdysteroids were detectable by radioimmunoassay in almost all of these
      concentrated samples. Thus, all lines of evidence point to the conclusion that
      all species of plants have the capacity to produce at least low levels of
      phytoecdysteroids. This has important implications for the protection of crop
      species through enhancing ecdysteroid levels by breeding/genetic modification
      strategies.

PMID- 11529506
TI  - 1Alpha,25-dihydroxyvitamin D3 inhibits hepatic chromosomal aberrations, DNA
      strand breaks and specific DNA adducts during rat hepatocarcinogenesis.
AB  - The possible promoting effect of streptozotocin (STZ; 65 mg/kg body weight,
      intraperitoneal)-induced diabetes during 2-acetylaminofluorene (2-AAF; 0.04% in
      basal diet)-initiated hepatocarcinogenesis and modulatory effect of 1alpha,25
      dihydroxyvitamin D3 (VD3; 0.3 microg/0.1 ml in propylene glycol, per os) were
      investigated by monitoring chromosomal aberrations (CAs), DNA strand breaks and
      specific DNA adducts in rat liver. VD3 treatment (twice a week) was started 4
      weeks before the 2-AAF regimen and continued throughout the study. Aberrant
      metaphase chromosomes were counted from the regenerating hepatocytes 15, 30 or 45
      weeks after STZ injection, while DNA strand break and adduct assays were
      performed 45 days post-STZ treatment. Dietary exposure to 2-AAF elicited a
      substantial increase in CAs and elevated the extent of DNA strand breaks and
      formation of N-(deoxyguanosin-8-yl)-2-aminofluorene. A promoting effect of STZ
      was evident from CAs coupled with DNA strand break analysis. VD3 treatment
      substantially reducted 2-AAF+STZ-induced CAs as well as DNA strand breaks and
      adducts. Thus, VD3 appears to be effective in suppressing liver-specific early
      chromosomal as well as DNA damage during the process of rat hepatocarcinogenesis
      initiated with 2-AAF and promoted by STZ contributing to its promise as a cancer
      chemotherapeutic agent.

PMID- 11529507
TI  - Culture in low levels of oxygen enhances in vitro proliferation potential of
      satellite cells from old skeletal muscles.
AB  - The proliferation ability of satellite cells (considered the 'stem cells' of
      mature myofibers) declines with increasing age when cultured under standard cell
      culture conditions of 21% oxygen. However, actual oxygen levels in the intact
      myofiber in vivo are an order of magnitude lower. No studies to date have
      addressed the issue of whether culturing satellite cells from old muscles under
      more 'physiologic' conditions would enhance their proliferation and/or
      differentiation ability. Therefore, we analyzed satellite cells derived from 31
      month-old rats in standard cultures with 21% O2 and in lowered (approximately 3%)
      O2. Under the lowered O2 conditions, we noted a remarkable increase in the
      percentage of large-sized colonies, activation of cell cycle progression factors,
      phosphorylation of Akt, and downregulation of the cell cycle inhibitor p27Kip1.
      These data suggest that lower O2 levels provide a milieu that stimulates
      proliferation by allowing continued cell cycle progression, to result ultimately
      in the enhanced in vitro replicative life span of the old satellite cells. Such a
      method therefore provides an improved means for the ex vivo generation of
      progenitor satellite cell populations for potential therapeutic stem cell
      transplantation.

PMID- 11529508
TI  - Phylogeography of crossbills, bullfinches, grosbeaks, and rosefinches.
AB  - Mitochondrial cytochrome b (cyt b) from 24 Carduelini species including
      crossbills, bullfinches, grosbeaks, rosefinches, and other related, but not
      conclusively classified species, was sequenced. These sequences were also
      compared with all the available sequences from the genera Carduelis, Serinus, and
      Passer. Phylogenetic analyses consistently gave the same groups of finches and
      the calculated divergence times suggest that speciation of the studied species
      occurred between 14 and 3 million years ago (Miocene-Pliocene), appearing before
      the Passer, Carduelis, and Serinus genera. Pleistocene glaciations may have been
      important in sub-speciation. Crossbills are integrated within the genus
      Carduelis, and within redpolls; the common crossbill shows subspeciation with
      Loxia japonica in the Pleistocene epoch. Pinicola enucleator groups together with
      bullfinches and is probably the ancestor of the group. Hawfinch is only distantly
      related to the studied groups, and might either represent an isolated genus or be
      related to the New World genus Hesperiphona. The grosbeak genera Eophona and
      Mycerobas are clearly sister groups, and species belonging to the former might
      have given rise to Mycerobas species. The isolated (in classification) Uragus
      sibiricus and Haematospiza sipahi are included within the genus Carpodacus
      (rosefinches); Carpodacus nipalensis is outside the genus Carpodacus in the
      molecular analyses and might be an isolated species or related to the genus
      Montifringilla.

PMID- 11529509
TI  - A health insurance tax credit for uninsured workers.
AB  - This paper describes a new system of tax credits to help low-income workers pay
      for health insurance. The system would be designed to subsidize health insurance
      coverage for workers who are currently uninsured, or who pay high premiums for
      nongroup insurance. Anyone age 19 or older who is not covered by Medicaid,
      Medicare, or employer-sponsored health insurance would be eligible for a health
      insurance tax credit (HITC), administered through the Internal Revenue Service.
      The base amount of the proposed credit would be $2,000 per year for each covered
      individual, but this amount would be adjusted for the individual's age and sex,
      according to the effect of age and sex on the cost of insurance coverage. The
      base amount of the credit would be reduced by $150 for every $1,000 by which a
      person's income exceeded 200% of the federal poverty level, thus limiting HITC
      eligibility to lower-income workers. To encourage participation in the credit
      program, most of the credit would be available through an advance payment system,
      with final reconciliation after year's end.

PMID- 11529510
TI  - Public subsidies for employees' contributions to employer-sponsored insurance.
AB  - Proposals to provide or subsidize health insurance for low-income families must
      take account of the fact that many workers have access to employer-sponsored
      insurance (ESI), but decline it because of required employee premium
      contributions. This article considers a tax credit for the employee share of ESI
      in the context of a broader program of income-based health insurance tax credits.
      Helping uninsured workers pay for available ESI could be more cost-effective than
      subsidizing their coverage in the nongroup market. The credit would also be
      available to workers who were already covered, both for equity reasons and to
      reduce the incentives for employers to drop coverage or for workers to shift to
      subsidized individual plans. One key issue is how to prevent employers from
      reducing their current health plan contributions to take advantage of the new
      funding. Other design questions considered by the article include whether workers
      should be able to choose between ESI and nongroup coverage, whether minimum
      benefit standards should apply for employer plans, and how to achieve a fair
      balance in subsidies for group and nongroup coverage.

PMID- 11529511
TI  - Markets for individual health insurance: can we make them work with incentives to
      purchase insurance?
AB  - Simple income-based incentives to purchase health insurance (tax credits or
      deductions, or subsidies) are unlikely to succeed in significantly reducing the
      number of uninsured because income is not a good predictor of the extent to which
      individuals use medical service. Proposals to provide incentives to low-income
      people so they will purchase individual health insurance need to address the
      inherent tension between the interests of low-risk and high-risk people who rely
      on individual coverage. If carriers are forced to cover all applicants and to
      community rate premiums, low-risk people will drop coverage or not apply for it
      because premiums will exceed their expected need for insurance. Concern for
      people who currently have access to individual coverage calls for careful
      examination of options to permit incentive programs to succeed with the
      individual insurance markets. In particular, attention should focus on using
      alternatives to simple income-based subsidies to spread the burden of high-risk
      people's costs broadly, rather than impose the costs on low-risk people who
      purchase individual coverage. This paper describes three such alternatives. One
      uses risk adjustments and two rely on reinsurance so that carriers are
      compensated for the higher costs of covering high-risk people who use incentives
      to buy insurance. One alternative also permits risk selection by insurance
      carriers.

PMID- 11529512
TI  - Expanding access through public coverage: permitting families to use tax credits
      to buy into Medicaid or SCHIP.
AB  - A new tax credit to help low-income families and individuals purchase health
      insurance can address the problem of affordability, but will not overcome other
      barriers these populations face in obtaining coverage. This paper proposes that
      families have the option of using a new tax credit to buy into a state
      administered system such as Medicaid or the State Children's Health Insurance
      Program. This option has three advantages. First, it allows families to remain
      with a single health program and health plan as their income fluctuates. Second,
      it provides an alternative to the complex and confusing individual insurance
      market. This alternative is community rated, does not use underwriting, and
      allows health plan behavior to be monitored closely by the state. Third, it
      allows the state to act as a financial buffer-helping overcome the barrier to
      participation that cash-flow problems and year-end reconciliation concerns are
      likely to create among a low-income population. Many people would want to use
      their tax credit in the private market, but the buy-in option increases the
      likelihood that the tax credit approach would succeed.

PMID- 11529513
TI  - Private purchasing pools to harness individual tax credits for consumers.
AB  - While health insurance tax credits could help people who otherwise could not
      afford to purchase coverage, many might still find individual coverage too
      expensive and its marketplace dynamics bewildering. As an alternative, this paper
      outlines an approach using private purchasing pools for tax-credit recipients.
      The objective is to offer these individuals and families a choice among competing
      health plans, and provide many of the same advantages enjoyed by workers in large
      employer groups, such as relatively low administrative costs, no health rating,
      and an effective "sponsor." Some express optimism that private pools will emerge
      naturally and thrive as an option for individual tax-credit recipients. However,
      adverse selection and other individual health insurance market forces make this a
      dubious prospect. The approach presented here gives purchasing pools the same
      tool employer groups use to maintain stability and cohesion--a significant
      contribution that cannot be used elsewhere. The ability to offer health plans
      exclusive access to a sizable new, previously uninsured clientele--tax-credit
      recipients-would enable purchasing pools to attract health plan participation and
      thus overcome one major reason several state-directed pools for small employers
      have failed. To avoid other pitfalls, the paper also suggests private pool
      structures, as well as federal and state roles that seek to balance objectives
      for market innovation and choice with those for coverage-source stability and
      efficiency.

PMID- 11529514
TI  - Increasing health insurance coverage through an extended Federal Employees Health
      Benefits Program.
AB  - The Federal Employees Health Benefits Program (FEHBP) could be combined with
      health insurance tax credits to extend coverage to the uninsured. An extended
      FEHBP, or "E-FEHBP," would be open to all individuals who were not covered
      through work or public programs and who also were eligible for the tax credits on
      the basis of income. E-FEHBP also would be open to employees of very small firms,
      regardless of their eligibility for tax credits. Most plans available to FEHBP
      participants would be required to offer enrollment to E-FEHBP participants,
      although premiums would be rated separately. High-risk individuals would be
      diverted to a separate high-risk pool, the cost of which would be subsidized by
      the federal government. E-FEHBP would be administered by the states, or if a
      state declined, by an entity that contracted with the Office of Personnel
      Management. While E-FEHBP would provide group insurance to people who otherwise
      could not get it, premiums could exceed the tax-credit amount and some people
      still might find the coverage unaffordable.

PMID- 11529515
TI  - Allowing small businesses and the self-employed to buy health care coverage
      through public programs.
AB  - The large number of uninsured working Americans and the extent of public support
      enjoyed by employment-based health insurance argues for a coverage initiative
      that fosters access to affordable benefits through employment. This proposal,
      which reflects models in both Massachusetts and Michigan, entails the development
      of publicly organized and subsidized group health insurance for small firms with
      low-wage workers. States would provide overall administration and subsidies to
      both employers and employees. Employers would enroll workers, select insurers,
      pay premiums, and report data on employment status. The program would be a
      legislative extension of the State Children's Health Insurance Program (SCHIP),
      with federal financing to participating states at each respective SCHIP rate.
      Anti-crowd-out provisions would be included. This program is both
      administratively and politically feasible. It is also consistent with current
      thinking regarding public/private partnerships and the desirability of preserving
      a voluntary employer-sponsored health insurance system.

PMID- 11529516
TI  - A federal tax credit to encourage employers to offer health coverage.
AB  - Many firms that employ low-wage workers cannot afford to offer an employee health
      plan, and many of the uninsured work for such firms. This article makes the case
      for an employer tax credit, administered by the Internal Revenue Service, as a
      way to extend health coverage to uninsured workers and their families. The
      permanent, fixed-dollar, refundable credit would be available to all low-wage
      employers (those with average wages of $10 per hour and less), including those
      already offering coverage. The credit would be graduated depending on average
      wage: the maximum credit would equal 50% of the cost of a standard benefit
      package; the minimum would equal 30% of the package. It also would vary by family
      size and could be used to cover part-time and temporary workers. Participating
      employers would be required to pay at least 50% of the health insurance premium,
      proof of which would be shown on firms' tax returns. The paper provides
      justification for this approach. It closes with a discussion of strengths and
      weaknesses of this approach and alternative design features.

PMID- 11529517
TI  - A workable solution for the pre-Medicare population.
AB  - Incremental reforms to expand health coverage among older Americans are justified
      by medical spending that increases with age and enrollment in employer insurance
      that decreases with age. Older Americans are also at risk of unexpected changes
      in health, access to health insurance, and earnings that could leave them poorly
      positioned financially for their retirement years. We propose offering universal
      access to Medicare at a community-rated premium, with premium vouchers for those
      with a history of low lifetime earnings and tax-preferred savings accounts to
      help everyone with the increased cost of insurance at older ages. These subsidies
      are available for coverage obtained from sources other than Medicare. We would
      set the eligibility age for the buy-in at 62. However, because enrollment in
      employer insurance does not drop precipitously at age 62, we regard the
      eligibility age as an adjustable design element that could resize the program to
      fit political and budgetary constraints.

PMID- 11529518
TI  - Transitional subsidies for health insurance coverage.
AB  - Losing or leaving a job often means losing health insurance. Of all those who
      have lost private insurance and become uninsured, one-third have either left or
      lost a job in the recent past. Continuation of coverage subsidies under the
      Consolidated Omnibus Budget Reconciliation Act (COBRA) of 1985 mitigate only
      slightly this problem due to the high costs of the group coverage that must be
      purchased. This paper discusses a proposal to build on the successes of COBRA to
      extend insurance to this important population. The key components are: a doubling
      of the length of COBRA entitlement to 36 months; eligibility for workers in all
      firms, not just those with more than 20 employees, but with a waiting period of
      one to two years; the establishment of a new COBRA-LOAN program that would offer
      government loans to help enrollees pay the cost of COBRA while they searched for
      new opportunities; and forgiveness of repayments after the entitlement period for
      those with low incomes.

PMID- 11529519
TI  - Challenges and options for increasing the number of Americans with health
      insurance.
AB  - This paper provides an overview of the issues confronting policymakers who want
      to develop programs to help working Americans obtain health insurance. It sets
      the stage for the following 10 articles, which detail a variety of proposals to
      offer subsidies and financial incentives to people so they will purchase health
      coverage. This paper examines challenges to covering the uninsured, describes
      principles that should be used in assessing policy proposals aimed at this
      purpose, and evaluates the main strategies for coverage expansions. The
      evaluation of proposal categories also provides estimates of the costs and
      consequences of specific proposals described in the other papers.

PMID- 11529520
TI  - Phonological, semantic, and repetition priming with homophones.
AB  - The current study investigated semantic, repetition, and phonological priming
      using heterographic homonyms (homophones) as stimuli in a lexical decision task.
      As in previous research, reliable semantic priming and repetition effects were
      found In addition, the statistical additivity of these two effects was replicated
      using homophones as stimuli. Using homophones, a reliable phonological priming
      effect was found when 10-16 intervening trials were used This effect was also
      statistically independent of semantic priming indicating the independence of the
      mechanisms responsible for semantic and phonological priming. The magnitude of
      the phonological priming effect was also significantly less than the magnitude of
      the repetition effect. This difference in effect magnitude was taken to indicate
      that the repetition of phonological information is not a primary contributor to
      the repetition effect.

PMID- 11529521
TI  - Prosodic structure and wh-questions.
AB  - This study examines the influence of wh-gaps on the prosodic contour of spoken
      utterances. A previous study (Nagel, Shapiro, & Nawy, 1994) claimed that the
      phonological representation of a sentence containing a filler-gap dependency
      explicitly encodes the location of the syntactic gap. In support of this
      hypothesis, Nagel et al. presented evidence that the word immediately preceding a
      gap is lengthened and that there is a reliable increase in pitch excursion across
      the gap location. Our study challenges Nagel et al.'s claim. We argue that their
      materials confounded the presence/ absence of a gap with other factors that are
      known to affect intonational phrasing independently. We show that, when these
      factors are separated, the evidence that syntactic gaps are explicitly encoded in
      the phonological representation of a sentence disappears.

PMID- 11529522
TI  - Constraints upon word substitution speech errors.
AB  - We explore the features of a corpus of naturally occurring word substitution
      speech errors. Words are replaced by more imageable competitors in semantic
      substitution errors but not in phonological substitution errors. Frequency
      effects in these errors are complex and the details prove difficult for any model
      of speech production. We argue that word frequency mainly affects phonological
      errors. Both semantic and phonological substitutions are constrained by
      phonological and syntactic similarity between the target and intrusion. We
      distinguish between associative and shared-feature semantic substitutions.
      Associative errors originate from outside the lexicon, while shared-feature
      errors arise within the lexicon and occur when particular properties of the
      targets make them less accessible than the intrusion. Semantic errors arise early
      while accessing lemmasfrom a semantic-conceptual input, while phonological errors
      arise late when accessing phonological forms from lemmas. Semantic errors are
      primarily sensitive to the properties of the semantic field involved, whereas
      phonological errors are sensitive to phonological properties of the targets and
      intrusions.

PMID- 11529523
TI  - Verb frame frequency as a predictor of verb bias.
AB  - There is considerable evidence showing that the human sentence processor is
      guided by lexical preferences in resolving syntactic ambiguities. Several types
      of preferences have been identified, including morphological, syntactic, and
      semantic ones. However, the literature fails to provide a uniform account of what
      lexical preferences are and how they should be measured. The present paper
      provides evidence for the view that lexical preferences are records of prior
      linguistic experience. We show that a type of lexial syntactic preference, viz.,
      verb biases as measured by norming experiments, can be approximated by verb frame
      frequencies extracted from a large, balanced corpus using computational learning
      techniques.

PMID- 11529524
TI  - Testing the interdependence hypothesis among native adult bilingual Russian
      English students.
AB  - English and Russian are two different orthographies, the former being an opaque
      orthography, the latter being considered a direct letter-sound language. This
      study investigated the relationship between reading, syntactic, orthographic, and
      working memory skills in the two orthographies. Participants were first-year BA
      students of English (age range 25-30) at the University of Haifa who had
      completed high school in Russia. They were tested individually, in Russian and
      English, on working memory, spelling, oral cloze, visual condition, phonological
      condition, orthographic skills, word attack, and word identification. The results
      indicated positive significant correlations within and across languages, except
      for the orthographic skills and some of the correlations of the visual skills.
      The orthographic skills correlated highly significantly within each language but
      not across languages. Almost all the other linguistic skills correlated
      significantly within and across languages. Multiple regression procedures
      revealed that phonological and spelling skills in Russian, the first language,
      were strong predictors of word identification in English, the second language.
      These results are discussed in light of the interdependence and the script
      dependent hypotheses.

PMID- 11529525
TI  - Does low birthweight facilitate postinfectious focal renal scarring?

PMID- 11529526
TI  - Problems in the diagnosis of neonatal hip instability.

PMID- 11529527
TI  - Prediction of outcome after wheezing in infancy.

PMID- 11529528
TI  - Eosinophil counts and urinary eosinophil protein X in children hospitalized for
      wheezing during the first year of life: prediction of recurrent wheezing.
AB  - Early identification of wheezing children with an increased risk of recurrent
      wheezing or subsequent asthma is important. The aim of the study was to determine
      the role of markers of eosinophil activation, along with other parameters, in the
      prediction of recurrent wheezing and allergic sensitization in children with
      early and severe wheezing. We examined 105 children without atopic dermatitis,
      hospitalized for wheezing during the first year of life. At a 20-mo follow-up,
      101 of the children were assessed for the occurrence of recurrent wheezing (at
      least 3 episodes, including 1 in the previous 6 mo) and allergic sensitization
      (positive skin-prick test). By univariate analysis, levels of eosinophil counts
      at the time of hospitalization (p = 0.005, OR = 18.9), age in months (p < 0.0001,
      OR = 1.5), respiratory syncytial virus (RSV)-negative disease (p < 0.0001, OR =
      8.8), parental atopy (p = 0.006, OR = 3.3) and male sex (0.02, OR = 2.7) were all
      predictive factors for recurrent wheezing at follow-up. With all parameters
      included in a multiple regression analysis, RSV-negative disease was not a
      predictive factor for recurrent wheezing. A simple model including eosinophil
      counts > or = 0.1 x 10(9)/L and age had a predictive accuracy of 79%, with only a
      6% chance of a child being wrongly predicted as symptomatic. Urinary protein X (U
      EPX) was not a predictive factor for recurrent wheezing. When included in a
      multiple logistic regression analysis, a level of U-EPX > or = 100 microg/mmol
      creatinine was the only parameter with a positive predictive value for allergic
      sensitization (p = 0.007, OR = 18.9), whereas age, parental allergy or parental
      asthma were not. CONCLUSION: Children with severe wheezing during the first year
      of life and subsequent recurrent wheezing are characterized by a normal or high
      eosinophil count in response to viral infections.

PMID- 11529529
TI  - Food allergy and atopic dermatitis in low birthweight infants during early
      childhood.
AB  - The prevalence rates of food allergy and atopic dermatitis in low birthweight
      infants were evaluated. In Fukuoka City, Japan, between July 1994 and September
      1997, sufficient information including birthweight, gestational age, sex, feeding
      method and a history of food allergy was obtained from questionnaires at the well
      baby check-ups of 21766 infants (18 mo of age) and 4378 children (3 y of age).
      All the children were examined by pediatricians with regard to the existence of
      atopic dermatitis. The prevalence rate (8.1%) of food allergy in infants with low
      birthweight (<2,500 g) was significantly lower than that (11.2%) in infants with
      normal birthweight (> or = 2,500 g) at 18 mo of age (p = 0.0002). Atopic
      dermatitis was also observed at a lower prevalence rate (1.2%) in infants with
      low birthweight than in those with normal birthweight (2.3%) at the same age (p =
      0.0041). However, this significance was lost at 3 y of age. Other characteristics
      including male sex and breast-feeding showed independent risks for the
      development of food allergy and atopic dermatitis at both ages. CONCLUSION: This
      study found that low birthweight was significantly associated with a lower risk
      of both food allergy and atopic dermatitis at 18 mo of age.

PMID- 11529530
TI  - Hyperinsulinism in syndromal disorders.
AB  - Analysis of a German database comprising a total of 54 patients with neonatal
      manifestations of persistent hyperinsulinism revealed 5 patients in whom
      hyperinsulinism was associated with additional clinical symptoms, suggesting an
      underlying syndromal disorder. Three of the patients presented with a similar yet
      unknown clinical entity characterized by severe psychomotor retardation, chronic
      pulmonary disease, hypothyroidism and congenital heart defects. A fourth patient
      was affected by severe congenital central hypoventilation syndrome. The fifth
      patient presented with Beckwith-Wiedemann syndrome, with unusually severe and
      persistent hyperinsulinism requiring subtotal pancreatectomy. CONCLUSION: Our
      results indicate that, in addition to the well-known biochemical pathways, more
      complex pathophysiological mechanisms can result in persistent hyperinsulinism
      that presents clinically with a disease involving multiple organs.

PMID- 11529531
TI  - Cystic fibrosis-related diabetes mellitus: clinical impact of prediabetes and
      effects of insulin therapy.
AB  - In patients with cystic fibrosis (CF), glucose intolerance preceding diabetes
      (prediabetes) may have adverse effects on nutritional status and respiratory
      function, which are reversible after the start of insulin therapy. Respiratory
      function (forced vital capacity and forced expiratory volume in one second) and
      body mass index (BMI) were compared retrospectively in a French cohort of 14
      patients during the 5 y preceding insulin therapy for diabetes and in 14 age- and
      sex-matched controls with normal oral glucose tolerance tests. In the diabetic
      group, all three parameters deviated increasingly from the values in the
      controls; the differences became statistically different during the 6 mo before
      insulin therapy. The effect was more important in patients for whom diabetes
      mellitus was diagnosed on the basis of symptoms of hyperglycaemia than in
      patients for whom it was diagnosed by systematic screening, but still present in
      the latter. After insulin was started, respiratory function improved and the BMI
      returned to normal within 1 y. The annual insulin requirement increased from 0.62
      during the first year to 1.25 during the fifth year. Glycosylated haemoglobin
      (HbAIc) values ranged from 6.6 to 7.8%. Only 2 episodes of severe hypoglycaemia
      were recorded over 42 patient-years of follow-up. The insulin regimen most often
      used was two daily injections of a mixture of short- and intermediate-acting
      insulin (n = 10) given with an insulin pen. CONCLUSION: The clinical status of CF
      patients who will need insulin therapy deteriorates before the start of insulin.
      In patients with CF-related diabetes, with or without fasting hyperglycaemia,
      insulin therapy improves anabolism and provides good glycaemic control with few
      severe hypoglycaemic episodes.

PMID- 11529532
TI  - Insulin-like growth factor-I and insulin-like growth factor-binding protein-3 in
      cystic fibrosis: a positive effect of antibiotic therapy and hyperalimentation.
AB  - Patients with cystic fibrosis (CF) are underweight and growth retarded. This
      study tested the link between serum insulin-like growth factor-I (IGF-I) and
      insulin-like growth factor-binding protein-3 (IGFBP-3) levels and body height,
      nutritional status, pulmonary function tests and activity of inflammation in 92
      subjects with CF (age 2.1-18.8 y). It also analysed the effect of short-term
      antibiotic treatment and hyperalimentation on IGF-I and IGFBP-3 levels in 33
      subjects (age 3.6-33.7y) on 41 occasions. Both IGF-I (-1.19 +/- 0.17 SD) and
      IGFBP-3 levels (-0.66 +/- 0.12 SD; both p < 0.0001 vs 0) were decreased in cross
      sectional measurements. Their standardized values were inversely proportional to
      age (IGF-I: r = -0.23, p = 0.03; IGFBP-3: r = -0.29, p = 0.005) and positively
      correlated with SDS of height (IGF-I: r = 0.40, p < 0.0001; IGFBP-3: r = 0.36, p
      = 0.0005) and of mid-arm circumference (IGF-I: r = 0.39, p = 0.0001; IGFBP-3: r =
      0.38, p = 0.0002), and with pulmonary function tests. After a short-term course
      of intensive antibiotic therapy and hyperalimentation, IGF-I normalized (from 
      0.66 +/- 0.20 to 0.00 +/- 0.25 SD; p < 0.0001) and IGFBP-3 increased (from -0.78
      +/- 0.15 to -0.53 +/- 0.16 SD; p = 0.002). IGFBP-3 correlated inversely with
      erythrocyte sedimentation rate (r = -0.40, p = 0.01). CONCLUSION: The levels of
      IGF-I and IGFBP-3 are markedly decreased in patients with CF and tend to
      normalise after a short course of antibiotic treatment and hyperalimentation.

PMID- 11529533
TI  - Acid steatocrit: a reliable screening tool for steatorrhoea.
AB  - This study compared the acid steatocrit (AS) results of healthy children with
      those of sick children with and without gastrointestinal involvement. Stool
      samples of 166 children were investigated, comprising 50 healthy children, 26
      asthma patients, and 90 patients with gastrointestinal problems divided into 34
      treated cystic fibrosis (CF) patients with exocrine pancreatic insufficiency, 16
      untreated coeliac disease (CD) patients and 40 patients with various
      gastrointestinal problems. The median values (5th-95th percentile) of AS results
      were 3.3% (0.0-21%) for healthy children, 4.5% (1.8-22.5%) for asthma patients,
      24.7% (2.6-68.2%) for treated CF patients with exocrine pancreatic insufficiency,
      19.8% (3-77.7%) for untreated CD patients and 5.5% (1.8-29%) for patients with
      various gastrointestinal diseases. CONCLUSION: The AS results of treated CF
      patients with exocrine pancreatic insufficiency and untreated CD patients were
      similar and significantly higher than those of healthy children and asthma
      patients. AS can be considered to be a reliable tool in screening for
      steatorrhoea in paediatric patients.

PMID- 11529534
TI  - Small bowel capsule biopsy in children: parents' opinions on children's
      discomfort.
AB  - This questionnaire study asked the parents of 62 children undergoing small bowel
      capsule biopsy for their reactions to the discomfort experienced by their
      children. The children were randomized to receive sedation with midazolam either
      intravenously or intranasally. With regard to the biopsy procedure the parents of
      94% of the children had no objections. The parents of 3% of the children found
      the biopsy very unpleasant and another 3% suggested that the biopsy should be
      performed under general anaesthesia. The proportion of parents with negative
      reactions to the biopsy procedure did not differ significantly between the
      intravenously and intranasally sedated children. With regard to the sedation
      given, the parents of 79% of the children did not think that their children were
      in any discomfort at all. Ten percent of the children had obvious signs of nasal
      discomfort using the intranasal administration. In the remaining 11% of the
      children the parents reported various symptoms. CONCLUSION: The vast majority of
      parents of children undergoing small bowel capsule biopsy found the procedure
      satisfactory providing that the sedative medication was given intravenously
      rather than intranasally.

PMID- 11529535
TI  - Gastrin, somatostatin and infantile hypertrophic pyloric stenosis.
AB  - Despite multiple and often contradictory research, no firm conclusions regarding
      the role of hypergastrinaemia in infantile hypertrophic pyloric stenosis (IHPS)
      have been established. Evaluation of somatostatin, the main physiological
      antagonist of gastrin, has not been assessed in previous studies. Long-term
      evaluation following pyloromyotomy suggests persistent abnormalities in gastrin
      and somatostatin in IHPS. The objective of this case-controlled study was to
      compare fasting serum gastrin and somatostatin levels in IHPS. Serum sample were
      collected from 39 children with IHPS at the time of pyloromyotomy and 20 age
      matched controls with no evidence of gastrointestinal disease. Standard
      radioimmunoassay techniques were used to detect circulating levels of the
      hormones. A two-tailed t-test was used for statistical analysis. The levels of
      the two hormones (mean +/- SEM) revealed that there was no evidence of
      hypergastrinaemia in IHPS compared with controls (75.6 +/- 16.1 and 68.1 +/- 7.8
      ng l(-1), respectively), but that the level of somatostatin was significantly
      elevated (38.9 +/- 6.4 and 30.5 +/- 5.8 ng l(-1), p = 0.016). An inverse trend in
      the gastrin/somatostatin levels could not be identified in IHPS. CONCLUSION:
      Somatostatin but not gastrin is raised in IHPS. Somatostatin is known to inhibit
      the actions of inhibitory neurotransmitters in the pylorus and may explain the
      development of pylorospasm, which is believed to be important in the development
      of pyloric tumours. These results do not agree with a previous long-term follow
      up study, but reflect the hormonal imbalance at the time of pyloric hypertrophy.

PMID- 11529536
TI  - Effect of enteral nutrition on antioxidant enzyme systems and inflammation in
      paediatric Crohn's disease.
AB  - Crohn's disease is characterized by chronic inflammation of the gastrointestinal
      mucosa, which can be successfully treated with enteral nutrition. In this study,
      the activities of the antioxidant metalloenzymes copper/zinc-superoxide dismutase
      (Cu/Zn-SOD) and selenium-glutathione peroxidase (Se-GPx) were determined in
      erythrocyte lysates from children with Crohn's disease. Both enzymes exhibited
      significantly lower activities relative to healthy control subjects: 1.55 +/-
      0.33 vs 2.13 +/- 0.75 SOD U mg(-1) protein (p < 0.025) for Cu/Zn-SOD, and 61.9 +/
      17.7 vs 93.6 +/- 28.7 mU mg(-1) protein (p < 0.01) for Se-GPx. Treatment of
      patients with a specific polymeric diet, CT3211, for a period of 8 wk did not
      significantly alter the activities of the enzymes. In contrast, clinically,
      enteral nutritional therapy induced a remission in 13/14 children, and a
      significant fall in both median serum C-reactive protein and mean serum tumour
      necrosis factor-alpha levels. CONCLUSION: The results imply that the anti
      inflammatory action of enteral nutrition in Crohn's disease is caused by a
      mechanism other than restitution of these antioxidant enzymes.

PMID- 11529537
TI  - Growth hormone treatment in children with Noonan's syndrome: four year results of
      a partly controlled trial.
AB  - The aim of the study was to evaluate the effect of continuous and discontinuous
      growth hormone treatment in Noonan's syndrome (NS) on linear growth and bone
      maturation. Thirty-seven children with NS aged between 5.4 and 17.5 y were
      treated with growth hormone (GH) in a dose of 0.15 IU kg)(-1) per day; 23 of
      these children were randomly assigned to one of 2 groups in a 3 y partly
      controlled prospective multicentre study. Group A (n = 8) immediately started GH
      treatment and after 2 y discontinued GH treatment for 1 y; group B (n = 15)
      served as a control group during the first year and started GH treatment after 1
      y. After the 3 y study period, 17 out of the 23 children continued GH treatment.
      An additional 14 children (group C) were treated according to the same protocol,
      but without discontinuation of GH treatment. The effect of GH treatment for up to
      3 y was evaluated in terms of gain in height standard deviation score (H-SDS) for
      calendar age and for bone age. Gain in H-SDS over the first year was
      significantly higher in the GH treatment group (+0.5) than in the non-treated
      group (+0.0); mean bone maturation was significantly faster in the GH treatment
      group (1.2 vs 0.5 y/y). Discontinuation in group A in the third study year
      resulted in catch-down growth (mean deltaH-SDS -0.2). Over 3 y of GH treatment,
      mean AH-SDS for calendar age was not significantly different between
      discontinuous (A: +0.8) and continuous treatment (B: +0.8; C: +1.2). Mean gain in
      H-SDS for bone age in the 3 groups (+0.2, 0.0. +0.3) was minimal after 3 y of GH
      treatment. CONCLUSION: This study confirmed the gain in H-SDS CA in Noonan's
      syndrome during long-term GH treatment. However, the accelerating effect of GH on
      bone maturation seemed to compromise the final height prognosis.

PMID- 11529538
TI  - The breech presentation and the vertex presentation following an external version
      represent risk factors for neonatal hip instability.
AB  - The aim of this study was to evaluate the frequency and type of hip-joint
      instability and the frequency of hip dislocation requiring treatment in neonates
      who had been lying in the breech presentation and were delivered vaginally after
      an external version or by caesarean section, and to compare them with neonates
      who were naturally in the vertex presentation. Breech presentations without
      ongoing labour were subjected to an attempted external version and, in cases
      where this proved unsuccessful or where labour had started, to deliver by
      caesarean section. None of the breech presentations was vaginally delivered. The
      anterior-dynamic ultrasound method was used to assess the hip-joint status of the
      neonates. Out of 6,571 foetuses, 257 were in breech presentation after 36 wk of
      pregnancy. Sixty-two were vaginally delivered following an external version to
      vertex presentation and 195 were delivered by caesarean section, 75 of these
      following unsuccessful attempts to perform a version. Treatment for congenital
      hip-joint dislocation was performed on 0.2%. Out of the breech presentations,
      1.0% of those delivered by caesarean section were treated, while in those with
      vaginal delivery following an external version the treatment frequency was 3.2%.
      No case of late diagnosed hip dislocation was recorded. Significant differences
      in frequency of hip-joint instability and treatment were found between (i)
      neonates delivered in breech presentation and those delivered with vertex
      presentation, (ii) infants delivered in vertex presentation, naturally or after
      successful version, and (iii) those delivered by caesarean section with or
      without attempted external version and those delivered with vortex presentation.
      CONCLUSION: Breech presentation predisposes to increased hip instability. The
      instability is present prior to delivery and is certainly not a primary result of
      delivery forces. Both breech and vertex presentations following an external or
      spontaneous version should be considered as risk factors for neonatal hip
      instability.

PMID- 11529539
TI  - Transcutaneous bilirubinometry in preterm infants.
AB  - The aim of this study was to evaluate the accuracy and safety of transcutaneous
      bilirubinometry in preterm infants using the new bilirubin analyser BiliCheck.
      The study included 145 preterm children (23-36 wk gestation). Capillary blood
      sampling for determination of serum bilirubin (BS) was combined with
      transcutaneous bilirubin measurement (BTc) every morning until the sixth
      postnatal day and related to several clinical data (phototherapy (PT), infection
      signs, breathing disturbances, skin bleeding, etc.). Overall bilirubin
      concentration ranged from 17 to 371 micromol/l, and from 21 to 325 micromol/l for
      BS and BTc, respectively. Mean values obtained by BTc were significantly higher
      than BS values. The correlation coefficient between BS and BTc was r= 0.64 for
      the whole group, and r = 0.73 in infants without PT. As demonstrated by multiple
      regression analysis, BS-BTc correlations were related only to gestational age
      (beta -0.32) and breathing disturbances (beta 0.29), indicating that the lower
      the gestational age and the more seriously ill the baby, the higher the
      incoherence between BS and BTc. CONCLUSION: BiliCheck provides a convenient, non
      invasive possibility for bilirubin estimation in preterm infants. However, there
      are limitations: the method gives reliable results only in newborns older than 30
      wk gestation, without PT and artificial ventilation.

PMID- 11529540
TI  - A placebo-controlled trial of low-dose erythromycin to promote feed tolerance in
      preterm infants.
AB  - The aim of this study was to assess the efficacy of erythromycin, a motilin
      agonist, in promoting enteral feed tolerance in preterm infants of < or = 32 wk
      gestation. Eligible infants were randomized to receive either low-dose (2.5 mg
      kg(-1) per dose 6 hourly) oral erythromycin ethylsuccinate or placebo for 10 d
      from the time of the first oral feed. The data from 22 erythromycin and 21
      placebo infants were analysed. Birthweights (erythromycin 1,216 +/- 380 g,
      placebo 1,355 +/- 228 g, p = 0.25), gestation (erythromycin 28.6 +/- 2.2 wk,
      placebo 29.3 +/- 1.7 wk, p = 0.24) and other clinical variables were not
      different between the groups. Almost all infants were fed expressed breast milk.
      Erythromycin infants had significantly fewer episodes of large residual gastric
      aspirates (>30% of the previous 6 h worth of feeds) over 10 d (erythromycin 1.1
      +/- 1.9, placebo 3.6 +/- 2.2 episodes, p = 0.0007). Infants in the erythromycin
      group achieved full oral feeds more quickly (6.0 +/- 2.3 vs 7.9 +/- 3.5 d, p =
      0.04). There were no significant differences between the groups with regard to
      the number of days on total parenteral nutrition or to the time needed to regain
      birthweight. One enrolled infant from each group died of necrotizing
      enterocolitis. CONCLUSION: Low-dose erythromycin promoted gastric emptying and
      feed tolerance in premature infants at a lower gestational age than previously
      reported. Increased exposure to broad-spectrum antibiotics may not be free of
      risk. Further studies are recommended to assess its efficacy in premature infants
      with established feed intolerance.

PMID- 11529541
TI  - Brainstem size and function at term age in relation to later neurosensory
      disability in high-risk, preterm infants.
AB  - The aim of this study was to measure brainstem size on magnetic resonance imaging
      (MRI) scans of high-risk. preterm infants, to assess brainstem function by
      brainstem auditory-evoked potentials (BAEP) and to determine the predictive value
      of these measures for the neurosensory outcome. A total of 51 preterm infants
      (gestational age <34 wk, birthweight <1,500 g) underwent examinations at term
      age; neuromotor outcome and hearing were followed up until a corrected age of 18
      mo. Fourteen (27%) infants had neurosensory disability. Those with a later
      neurosensory disability had a significantly smaller brain stem than those with a
      normal outcome. The preterm infants had significantly longer peak latency (L) V
      and interpeak latency (IPL) III-V than the full-term control infants. Most of the
      preterm infants with severe cerebral palsy or hearing loss had abnormal BAEP.
      Sensitivity of morphometric dimensions for predicting neurosensory disability was
      only 20-31%, but specificity was 97-100%. Abnormal L I and IPL III-V in BAEP
      predicted disability with a sensitivity of 93% and a specificity of 57-59%.
      CONCLUSION: We conclude that adverse events during the perinatal period may lead
      to morphofunctional changes in the brain stem in high-risk, preterm infants, and
      it seems that functional changes are accurate in predicting neurosensory
      disability in such patients.

PMID- 11529542
TI  - Adverse events following vaccination in premature infants.
AB  - The aims of this study were to study the frequency, severity and types of adverse
      reactions following DPT/Hib (diphtheria and tetanus toxoids and
      pertussis/Haemophilus influenzae type B conjugate) immunization in very preterm
      infants and to identify possible risk factors. Case notes of 45 preterm babies
      vaccinated in the neonatal intensive care unit between January 1993 and December
      1998 were studied retrospectively. Birthweight, gestational age, duration of
      ventilation, oxygen dependency, timing of vaccination, weight, corrected
      gestation at vaccination and apparent adverse effects were noted. Apparent
      adverse events were noted in 17 of 45 (37.8%) babies: 9 (20%) had major events,
      i.e. apnoea, bradycardia or desaturations, and 8 (17.8%) had minor events, i.e.
      increased oxygen requirements, temperature instability, poor handling and feed
      intolerance. Babies with major events were significantly younger (p < 0.05), had
      a lower postmenstrual age (p < 0.05) and weighed less (p < 0.05) at the time of
      vaccination compared with babies without major events. No differences in the mean
      birthweight, gestational age, duration of ventilation or oxygen dependency were
      found between the two groups. Age at vaccination of 70 days or less was
      significantly associated with increased risk (p < 0.01). Of 27 babies vaccinated
      at 70 days or less, 9 (33.3%) developed major events compared with none when
      vaccinated over 70 d. CONCLUSION: Vaccine-related cardiorespiratory events are
      relatively common in preterm babies. Problems were much more common if vaccine is
      administered at or before 70 d. These babies should therefore be monitored
      postvaccination. Further prospective studies are needed to clarify whether
      delaying vaccination offers protection against these adverse events.

PMID- 11529543
TI  - Effect of short-term antenatal dexamethasone administration on type I collagen
      synthesis and degradation in preterm infants at birth.
AB  - To assess the effects of antenatal corticoid administration on foetal collagen
      metabolism, cord serum concentrations of the aminoterminal propeptide and
      carboxyterminal telopeptide of type I procollagen (PINP and ICTP), which reflect
      rates of type I collagen synthesis and degradation, respectively, were measured
      in 67 consecutive preterm infants with gestational ages ranging from 24 to 32 wk.
      The samples were divided into three groups, depending on the administration and
      timing of antenatal corticosteroid treatment for enhancement of foetal lung
      maturity: cases in which the mothers had received a full 2-dose administration of
      dexamethasone on consecutive days 1 to 6 d before delivery (n = 23; Complete
      Dexa), those who had received only a single dose of dexamethasone less than 24 h
      before delivery (n = 17; Partial-Dexa) and those who had not received any
      antenatal steroids (n = 27; No-Dexa). Infants in the Complete-Dexa group had
      significantly lower median PINP levels than those in the No-Dexa group (3,326 vs
      4,028 microg/l; p = 0.036); the median PINP level in the Partial-Dexa group
      (3,999 microg/l) was close to that of the No-Dexa group. No significant
      differences in ICTP concentrations were seen between the groups. CONCLUSION: A
      significant suppression of foetal collagen synthesis but not degradation was
      found to be associated with antenatal dexamethasone administration. This should
      be taken into consideration, e.g. when assessing whether to administer repeated
      or single courses of corticosteroids antenatally in high-risk pregnancies.

PMID- 11529544
TI  - Impact of smoking on the duration of breastfeeding in mothers with insulin
      dependent diabetes mellitus.
AB  - The effect of smoking on breastfeeding was studied in 252 mothers with insulin
      dependent diabetes mellitus (IDDM) giving birth in the period 1985-1995 and of
      whom 31% were classified as White group B, 16% group C, 37% group D and 16% group
      F or R. As part of a centralized regimen a detailed smoking history was taken
      during pregnancy. Forty-six percent were smokers. In 1997, a questionnaire was
      sent out asking for information on the duration of breastfeeding. The response
      rate was 87%. The duration of breastfeeding was significantly longer in the non
      smoking group (p = 0.004). Fifty-five percent of non-smokers versus 33% of
      smokers were still breastfeeding 4 mo after birth. A strong dose-response
      relationship was established (p = 0.009). Cox multiple regression analysis showed
      a significantly negative influence of smoking (p = 0.01) and of hospitalization
      of the infants during the first year of life (p = 0.02) and a significantly
      positive influence of maternal age (p = 0.02) and birthweight (p = 0.03) on the
      length of breastfeeding. The breastfeeding curves for non-smokers and smokers
      were mainly divergent in the first month after birth, suggesting that the effect
      of smoking on breastfeeding is mainly exerted during that period. CONCLUSION:
      Smoking exerted a strong, negative, dose-dependent influence on breastfeeding
      duration in mothers with IDDM. Given the hazards of smoking, the advantages of
      breastfeeding and the possible link between being breastfed and later development
      of diabetes mellitus, these results should be taken into consideration when
      counselling pregnant women with IDDM about smoking.

PMID- 11529545
TI  - Duration of breastfeeding and associated factors in Western and Eastern Germany.
AB  - Ten years after the German political reunification, specific lifestyle habits
      still vary between the former Western (FRG) and Eastern (GDR) sectors of Germany.
      We have analysed data from the first nationwide SuSe Study on breastfeeding 1997
      1998 (n = 1593 healthy, term German infants) stratified in a Western (80.3%) and
      Eastern (19.7%) subgroup. In the Eastern subgroup, breastfeeding was higher for
      the first 2 wk but decreased more rapidly thereafter. The adjusted relative risk
      (odds ratios, OR) for short-term breastfeeding was strongly associated (OR >2)
      with maternal age, supplementary feeding, single parent status, maternal
      educational status, breastfeeding problems and partner's attitude towards
      breastfeeding. In the multivariate model, not the geographical location where the
      mother grew up but the different distribution of risk factors was associated with
      short-term breastfeeding. Moreover, mothers from both the Western and Eastern
      sectors mentioned different reasons for giving up breastfeeding. CONCLUSION: More
      breastfeeding promotion is necessary for women from the former GDR.

PMID- 11529546
TI  - Information and socioeconomic factors associated with early breastfeeding
      practices in rural and urban Morogoro, Tanzania.
AB  - A cross-sectional study was undertaken in a rural and an urban area in Tanzania
      with the aim of identifying factors related to early infant feeding practices.
      The study included 320 mothers from each area with infants below 7 mo of age. A
      significant proportion of both rural and urban mothers had erroneous beliefs
      about infant feeding practices. None of the socioeconomic, demographic or
      biological variables studied were associated with feeding practices. Urban
      residence was positively associated with the duration of exclusive but not
      predominant breastfeeding. Better knowledge about specific breastfeeding issues
      was positively associated with the duration of both exclusive and predominant
      breastfeeding. Ownership of a radio was positively associated with both exclusive
      and predominant breastfeeding in the rural area. Although both rural and urban
      mothers had a high antenatal clinic attendance rate, 65% of the rural and 14% of
      the urban mothers delivered at home. Urban mothers informed about breastfeeding
      at the antenatal clinic had better feeding practices. CONCLUSION: We hypothesize
      that exclusive breastfeeding is not a traditionally recognized practice and thus
      its duration is mainly associated with information and knowledge about
      breastfeeding. This suggests that information programmes to provide knowledge,
      beginning at antenatal visits, may reduce premature complementation, though
      additional support may also be required.

PMID- 11529547
TI  - Childhood and adolescent tuberculosis in northern Taiwan: an institutional
      experience during 1994-1999.
AB  - This study evaluated the clinical characteristics of childhood and adolescent
      tuberculosis (TB) at the end of the twentieth century in a referral children's
      hospital in northern Taiwan. The hospital charts were reviewed retrospectively of
      children/adolescents aged less than 18 y who were seen in a children's hospital
      in northern Taiwan between 1994 and 1999 and diagnosed with TB. A total of 62
      individuals was diagnosed during this period. The patients' demographic data,
      presenting symptoms, clinical features, bacteriological results, drug
      susceptibility and tuberculin skin-test results were analysed. Most diagnosed
      cases lay in one of two main age ranges, younger than 5 y and adolescents. The
      presenting symptoms of study subjects were typically non-specific. Bone
      involvement occurred for 21 patients (33.9%) and was the most common
      extrapulmonary manifestation. Mycobacterium tuberculosis was isolated from 47
      patients (75.8%). Five isolates were resistant to pyrazinamide, three to
      streptomycin and one to isoniazid, but no multidrug resistant isolates of TB were
      detected from culture-proven cases. Seventeen of 47 (36.2%) culture-proven
      patients revealed negative acid-fast staining initially but, subsequently, M.
      tuberculosis was isolated from various clinical specimens using a standard method
      at a later date. The tuberculin skin test was positive for 24 of 32 patients
      (75%) who received such an examination. CONCLUSION: Extrathoracic TB was more
      common in children below 5 y of age than their adolescent counterparts, and
      chiefly involved the peripheral long bones. The potential drug resistance of M.
      tuberculosis in childhood and adolescent TB did not appear to have been a major
      problem in northern Taiwan before the year 2000.

PMID- 11529548
TI  - Selective screening for neonatal galactosemia: an alternative approach.
AB  - No universal consensus exists for population-based neonatal screening for
      galactosemia. In our institution, selective screening for classical galactosemia
      is carried out on infants under 2 wk of age and those with symptoms suggestive of
      this disorder. Eighteen cases were diagnosed from 25,099 tests done; 17 were
      symptomatic at the time of diagnosis. CONCLUSION: We suggest that improved
      clinical vigilance and selective screening would identify most infants with
      severe galactosemia as early as a population-based program.

PMID- 11529549
TI  - Selenium status, kwashiorkor and congestive heart failure.
AB  - Selenium deficiency is associated with congestive heart failure (CHF) in
      geographic areas where dietary selenium intake is low and in individuals
      receiving total parenteral nutrition. Among 66 children with kwashiorkor
      (including marasmic-kwashiorkor), those who developed CHF had lower serum
      selenium concentrations than those who did not (32.9 +/- 8.3 vs 41.1 +/- 11.9
      microg/L, mean +/- SD, p = 0.03). This association was independent of serum
      albumin and selenium status was not associated with severity of symptoms,
      anthropometric indices or HIV infection. CONCLUSION: This association raises the
      possibility that selenium may contribute to CHF in washiorkor.

PMID- 11529550
TI  - Inhaled corticosteroids for maintenance treatment in childhood pulmonary
      sarcoidosis.
AB  - We present our experience with sequential oral and inhaled corticosteroid therapy
      in childhood pulmonary sarcoidosis. Fifteen children were followed-up for a mean
      of 7 y. Treatment consisted of oral prednisolone 2 mg/kg/d on initial diagnosis.
      After remission was reached, alternate day therapy with 1 mg/kg was continued.
      The dose was tapered to a maintenance dose which controlled the activity of the
      disease. When patients were free of symptoms and had no clinical and laboratory
      findings, inhaled corticosteriod treatment was started. Relapse treatment
      consisted of cessation of inhaled corticosteroids and start of oral
      corticosteroids at a dosage of 2 mg/kg/d and then a tapered dose. Five patients
      were given oral corticosteroids only. Nine patients were given inhaled steroids
      after oral corticosteroid therapy had been discontinued. Clinical and
      radiological remissions were achieved in every patient. CONCLUSION: Sequential
      oral and inhaled corticosteroid therapy may be an alternative treatment regimen
      for sarcoidosis in children.

PMID- 11529551
TI  - Cardiac troponin T in neonates.

PMID- 11529552
TI  - Effectiveness of haemofiltration in valproic acid intoxication.

PMID- 11529554
TI  - Morphological changes of the anterior spinal artery during aortic cross-clamping
      and effect of prostaglandin E1 with perfusion.
AB  - This investigation was designed to evaluate the morphological changes of anterior
      spinal artery (ASA) and its reaction to prostaglandinE1 (PGE1) during aortic
      cross-clamping. ASA during 30 min cross-clamping was observed with charge-coupled
      device (CCD) and ASA diameter (ASAD) was measured. Group A: Infrarenal aorta was
      cross-clamped. Group B: Infrarenal aorta was cross-clamped and aorta above the
      bifurcation was snared. The aortic segment between clamp and snare was perfused
      with blood. Group C: PGE1 of 100 ng/kg/min was added to perfusate of Group B. The
      aortic segmental pressures in group B and C were about 30% of the proximal
      systolic arterial pressure and were significantly higher than distal pressure of
      group A. After cross-clamping, ASAD decreased about 80% of before cross-clamping
      in group A. By segmental perfusion of which pressure was about 30% of proximal
      systolic arterial pressure, ASAD remained almost 90% in group B. By
      administration of PGE1, ASAD was significantly increased in group C. The changes
      of ASAD were significantly different between group A and C, and between group B
      and C.

PMID- 11529553
TI  - Effect of the aromatase inhibitor CGS-16949A on pregnancy and secretion of
      progesterone, estradiol-17beta, prostaglandins E and F2alpha (PGE; PGF2alpha) and
      pregnancy specific protein B (PSPB) in 90-day ovariectomized pregnant ewes.
AB  - The aromatase inhibitor CGS-16949A was used to determine whether CGS-16949A
      altered secretion of progesterone, estradiol-17beta, PGE (PGE1 + PGE2), PGF2alpha
      and PSPB. Ninety day pregnant ewes were ovariectomized and received vehicle,
      PGF2alpha, CGS-16949A or PGF2alpha+CGS-16949A. None of the ewes treated with
      PGF2alpha, CGS-16949A or PGF2alpha+CGS-16949A aborted (P > or = 0.05) during the
      108-h experimental period. Treatment with CGS-16949A lowered (P < or = 0.05)
      progesterone in jugular venous plasma but concentrations of progesterone were not
      affected (P > or = 0.05) by treatment with PGF2alpha. Concentrations of estradiol
      17beta and PSPB in jugular venous plasma and PGE in inferior vena cava plasma
      were decreased (P < or = 0.05) by treatment with CGS-16949A. Concentrations of
      PGF2alpha in inferior vena cava plasma were not affected (P > or = 0.05) by
      treatment with CGS-16949A. Decreases in estradiol-17beta occurred before
      decreases in PSPB, which was then followed by decreases in PGE (P < or = 0.05).
      It is concluded that these data support the hypothesis that estradiol-17beta
      regulates placental secretion of PSPB; PSPB regulates placental secretion of PGE;
      and PGE regulates placental secretion of progesterone during mid-pregnancy in
      ewes.

PMID- 11529555
TI  - Effects of fish oil and vitamin E on the antioxidant defense system in diet
      induced hypercholesterolemic rabbits.
AB  - This study was designed to investigate the effects of fish oil and vitamin E on
      the antioxidant defense system in hypercholesterolemic rabbits. A high fat and
      cholesterol diet, with or without supplement by fish oil and/or a vitamin E
      supplement, was fed to rabbits for 6 weeks. Compared to the reference diet of
      regular laboratory rabbit chow, a high fat and cholesterol-enriched diet
      increased atheroma formation, plasma lipid and peroxide levels, decreased blood
      glutathione levels, and reduced plasma glutathione reductase, glutathione
      peroxidase, and catalase activities. Fish oil supplementation significantly
      reduced atheroma and increased glutathione reductase and glutathione peroxidase
      activities and blood glutathione levels, but increased plasma lipid peroxide
      levels. Vitamin E supplementation of the fish oil diet enhanced the beneficial
      effects by increasing glutathione reductase activity and decreasing peroxide
      levels. These results indicate that a high fat and cholesterol diet attenuates
      blood glutathione levels and plasma antioxidant enzyme activities, which may
      account for some of its atherogenic properties. Consumption of fish oil enhances
      antioxidative defenses against the oxidative stress imposed by
      hypercholesterolemia, and vitamin E further enhances these beneficial effects.

PMID- 11529556
TI  - Engraftment of tonsillar mononuclear cells in human skin/SCID mouse chimera-
      validation of a novel xenogeneic transplantation model for autoimmune diseases.
AB  - Pustulosis palmaris et plantaris (PPP) has been considered as one of the typical
      tonsillar focal infections, based on the marked clinical improvement of the skin
      lesions after tonsillectomy. Despite the accumulation of data showing the
      clinical efficacy of tonsillectomy for this skin lesion, fundamental etiological
      and pathophysiological issues have yet to be addressed. One primary obstacle
      hindering investigators has been the lack of an appropriate animal model for this
      human skin disorder. In the early stage of PPP, it has been reported that
      lymphocytes, predominantly CD4+ T lymphocytes, infiltrate the palmar and plantar
      skins. However, the origin and mechanism of infiltration by these lymphocytes is
      not clear and there are very few reports on whether tonsillar mononuclear cells
      react directly with the skin. We have been intrigued by the ability to engraft
      human cells onto severe combined immunodeficiency (SCID) mice, together with the
      opportunity for long-term graft survival and ability to adoptively transfer
      various human immunocompetent cells. In this review, we addressed the existing
      deficiencies in our understanding of the relationship between tonsils and PPP by
      using emerging transplantation technology involving SCID mice.

PMID- 11529557
TI  - Helicobacter pylori DNA in drinking water in Japan.
AB  - Helicobacter pylori has been detected in drinking water in Peru and Sweden,
      suggesting the possibility of water-borne transmission. To date there have been
      few reports of H. pylori being detected in water; one was of the ureA gene of H.
      pylori in wells and springs in rural Japan. We examined water sampled in or near
      urban areas of Japan for H. pylori DNA by three assays using the polymerase chain
      reaction (PCR). Near Tokyo, samples were obtained: 10 of tap water, 6 of well
      water, 10 of river water, and 10 of sea water. Samples were filtered with
      membranes with 0.05- or 0.22-microm pores, which bacterial cells are caught by.
      Bacterial nucleic acids were extracted and purified and the PCR was done to
      amplify adhesin specific for H. pylori and the ureA gene, if present. Real-time
      PCR that measured the yield in terms of fluorescence was done with primers for
      16S rRNA. None of the samples of tap, river, or sea water contained adhesin, ureA
      or 16S rRNA. None of the 6 samples of well water contained adhesin or ureA, but 2
      of the 6 samples contained 16S rRNA. Some of the users of the well had had H.
      pylori infection in the past. H. pylori DNA was detected in well water and the
      users had been infected, so water-borne transmission via well water may occur
      even in towns in Japan.

PMID- 11529558
TI  - Role of V3 independent domains on a dualtropic human immunodeficiency virus type
      1 (HIV-1) envelope gp120 in CCR5 coreceptor utilization and viral infectivity.
AB  - The molecular mechanism of human immunodeficiency virus type 1 (HIV-1) entry into
      cells involves specific interactions between the viral envelope glycoprotein
      gp120 and two target cell proteins, CD4 and either CCR5 or CXCR4 chemokine
      receptors. In order to delineate the functional role of HIV-1 gp120 subdomains of
      dualtropic strains in CCR5 coreceptor usage, we used a panel of chimeric viruses
      in which the V1/V2 and V3 domains of gp120 from the dualtropic HIV-1(KMT) isolate
      were introduced either alone or in combination into the T-tropic HIV-1(NL4-3)
      background. These chimeric constructs were employed in cell-cell fusion and cell
      free virus infectivity assays using cell lines expressing CD4 and the CCR5
      chemokine receptor. In both assays, the V3 domain of HIV-1(KMT) but not the V1/V2
      domain proved to be the principal determinant of CCR5 coreceptor usage. However,
      in the cell-free viral infectivity assay although a chimeric virus with a
      combined V1/V2 and V3 domains of HIV-1(KMT) efficiently fused with coreceptor
      expressing cells, yet its infectivity was markedly diminished in CCR5 as well as
      CXCR4 expressing cells. Restoring a comparable level of infection of such
      chimeric virus required the C3-V5 domain from HIV-1(KMT) to be introduced. Our
      present findings confirmed that the V3 domain is the major determinant of fusion
      activity and cellular tropism, and demonstrated a dispensable role for the V1/V2
      domain. In addition the C3-V5 domain appeared to play an important role in viral
      infectivity when the corresponding V1/V2 and V3 domains are present.

PMID- 11529559
TI  - Mechanism of selective inhibition of respiratory syncytial virus by a
      benzodithiin compound (RD3-0028).
AB  - RD3-0028, a compound with a benzodithiin structure, was found to be a potent
      inhibitor of respiratory syncytial virus (RSV) replication. Its action is
      specific; no activity is seen against influenza A virus, measles virus, herpes
      simplex virus type 1 or 2, or human cytomegalovirus. A time-dependent drug
      addition experiment indicated that the antiviral activity occurs in the late
      stage of the RSV replication cycle, since this compound completely inhibited
      syncytium formation even when added up to 16 hr after the infection of cell
      monolayers at an MOI of 3. RD3-0028 had no direct virucidal effect on RSV.
      Western blotting analysis showed that RD3-0028 significantly decreased the amount
      of RSV proteins released into the cell culture medium. Moreover, five independent
      isolates of the RSV long strain were selected for growth in RD3-0028 (5-20
      microg/ml). These resistant viruses were more than 80-fold less sensitive to RD3
      0028 than the long strain. The F gene segment of each of these viruses was
      sequenced and in each case the mutant RNA segment contained at least one sequence
      alteration, converting asparagine 276 to tyrosine (F1 protein). These results
      suggest that RD3-0028 inhibits RSV replication by interfering with intracellular
      processing of the RSV fusion protein, or a step immediately thereafter, leading
      to loss of infectivity.

PMID- 11529560
TI  - Fate of Legionella pneumophila in macrophages of C57BL/6 chronic granulomatous
      disease mice.
AB  - We compared the intracellular survival and growth of Legionella pneumophila
      Philadelphia-1 in peritoneal macrophages obtained from A/J, C57BL/6, and X-linked
      chronic granulomatous disease (CGD) mice produced from C57BL/6 strain. The
      initial killing was observed in A/J and C57BL/6 macrophages at 2, 4 and 6 hr
      after in vitro phagocytosis, but not in the CGD macrophages. Thereafter, there
      was a 10-fold increase of CFU in A/J macrophages. The bacteria, however, did not
      proliferate in C57BL/6 and CGD macrophages at 24 or 48 hr after in vitro
      phagocytosis. These results suggest that effector molecules for the initial
      killing are a superoxide anion and its metabolites, and Lgn1 gene product
      inhibits the intracellular growth of L. pneumophila independently of NADPH
      oxidase.

PMID- 11529561
TI  - Identification of a H+/glucose and galactose symporter gene glt from Xanthomonas
      oryzae pv. oryzae.
AB  - We identified a glucose and galactose transporter gene from the plant-pathogenic
      bacterium Xanthomonas oryzae pv. oryzae. Sequence analysis indicated that the
      gene, named glt, encoded a polypeptide of 592 amino acid residues and the product
      was significantly homologous with members of the Na+/glucose cotransporter (SGLT)
      family from mammalian and bacterial origin, especially with vSGLT from Vibrio
      parahaemolyticus (50% identity). GLT functioned as a glucose and galactose
      transporter in an Escherichia coli mutant deficient in glucose and galactose
      transport activity. A protonophore inhibited the transport activity, suggesting
      that GLT is a H+-coupled glucose/galactose symporter.

PMID- 11529562
TI  - Immunomodulatory effect of gold sodium thiomalate on murine acquired
      immunodeficiency syndrome.
AB  - Induction of IL-2 production and increased expression of CD25 were observed in
      C57BL/10 mice after weekly treatment with gold sodium thiomalate (GST). LP-BM5
      murine leukemia virus (MuLV) infected mice treated with GST survived longer, had
      less cervical lymph node swelling, lower spleen weight, and fewer abnormalities
      in the expression of the cell surface markers, CD4, CD8a and CD45R/B220 on spleen
      cells than those that were not treated with GST. Thus, GST treatment may be
      beneficial through a decrease in disease progression via IL-2 induction in MuLV
      infected mice. This may have application in human immunodeficiency virus-infected
      individuals.

PMID- 11529563
TI  - Morphological variety of intracellular microcolonies of Legionella species in
      Vero cells.
AB  - Intracellular microcolonies of six Legionella species growing in Vero cells
      showed distinctly varied morphologies. The varieties were observed by light
      microscopy of Gimenez-stained, Legionella-infected Vero cells and by electron
      microscopy (EM). Legionella pneumophila Philadelphia-1 formed needle-shaped
      crystal-like microcolonies. Legionella bozemanii WIGA formed microcolonies like
      wool balls containing filamentous cells. In EM, these organisms proliferated in
      endosomes, which were adjacent to swollen rough endoplasmic reticula. Legionella
      oakridgensis OR-10 showed serpentine chains. Many mitochondria were observed
      around the microcolonies. Legionella jordanis BL-540 formed spherical moss-like
      microcolonies which were or were not surrounded by endoplasmic membranes.
      Legionella feeleii WO-44C spread throughout the cytoplasm without making
      clusters. Legionella dumoffii Tex-KL made big clusters that spread in the
      cytoplasm, a portion of which was outside the endosome membranes. These different
      morphologies imply diversity in modes of intracellular multiplication of
      Legionella spp.

PMID- 11529564
TI  - Concentration variability of halocarbons over an electronics industrial park and
      its implication in compliance with the Montreal protocol.
AB  - This work investigated fugitive emissions of anthropogenic halocarbons in a
      semiconductor and electronics industrial park in Taiwan using both flask and in
      situ measurement methods. Large concentration variabilities in methylchloroform,
      trichloroethene, and tetrachloroethene suggested substantial usage and emissions
      in the industrial park. While the variability of CFC-113, CCl4, and CFC-11 was
      rather small using the flask sampling technique, the in-situ method with its
      higher frequency, however, showed significantly larger variability arising from
      observing periodic emission episodes, which were highly correlated with wind
      direction and topography of the park.

PMID- 11529565
TI  - Enhanced airborne polychlorinated biphenyl (PCB) concentrations and chlorination
      downwind of Lake Ontario.
AB  - Air samples were collected simultaneously at three sites downwind of Lake Ontario
      and at a control site near Lake Erie from March to July of 1999. The Lake Erie
      site (Stockton, NY) had PCB concentrations similar to rural Integrated
      Atmospheric Deposition Network (IADN) sampling sites across the Great Lakes,
      exhibited limited seasonal variation, and approximates regional background.
      Samples taken along Lake Ontario's southeastern shore (Rice Creek and Sterling,
      NY) had elevated PCB concentrations averaging approximately 1 ng/m3 and were more
      chlorinated than air collected at IADN sites and at Stockton. Air samples from
      Potsdam (approximately 75 km inland) had similar concentrations but were less
      chlorinated. Clausius-Clapeyron plots revealed a strong correlation between PCB
      fugacity and temperature near Lake Ontario; however, the extent of chlorination
      of the air samples rules out volatilization from the lake as a major source. It
      is hypothesized that volatilization from local surfaces, enriched in higher
      chlorinated congeners by meteorological or geographic factors, drives both the
      concentration and composition of airborne PCBs along Lake Ontario's southeastern
      shore.

PMID- 11529566
TI  - Accumulation of atmospheric and sedimentary PCBs and toxaphene in a Lake Michigan
      food web.
AB  - Seston, sediment, settling organic matter, and food web members were collected
      from Grand Traverse Bay, Lake Michigan, between April 1997 and September 1998 to
      examine PCB and toxaphene biomagnification. Stable isotopes of nitrogen and
      carbon were analyzed in samples and used to establish trophic structure of the
      food web and to determine the importance of atmospheric versus sedimentary
      sources in delivering PCBs to the food web. Nitrogen isotopes were confounded by
      multiple variables in this system, particularly seasonal variation, and did not
      display a simple pattern of enrichment among trophic levels. However, delta13C
      displayed little seasonal variation and was positively correlated with PCB
      concentrations among food web members (r2 = 0.69). Plots of delta13C vs PCBs
      separate food web members into three distinct groupings comprised of
      invertebrates, primary forage fish, and predatory fish. Stable isotope values of
      the primary organic sources indicate that the atmosphere, and not the sediment,
      is the most likely source of PCBs to the food web of Lake Michigan. Additionally,
      we suggest that seston may be important in delivering PCBs to pelagic food web
      members and species that receive a majority of their nutrition through pelagic
      sources. In contrast, settling particles are implicated in delivering PCBs to
      benthic organisms and Mysis relicta.

PMID- 11529567
TI  - Geostatistical assessment and validation of uncertainty for three-dimensional
      dioxin data from sediments in an estuarine river.
AB  - Contaminated sediment management is an urgent environmental and regulatory issue
      worldwide. Because remediation is expensive, sound quantitative assessments of
      uncertainty aboutthe spatial distribution of contaminants are critical, butthey
      are hampered bythe physical complexity of sediment environments. This paper
      describes the use of geostatistical modeling approaches to quantify uncertainty
      of 2,3,7,8-tetrachlorodibenzo-p-dioxin concentrations in Passaic River (New
      Jersey) sediments and to incorporate this information in decision-making
      processes, such as delineation of contaminated areas and additional sampling
      needs. First, coordinate transformation and analysis of three-dimensional
      semivariograms were used to describe and modelthe directional variability
      accounting forthe meandering course of the river. Then, indicator kriging was
      employed to provide models of local uncertainty at unsampled locations without
      requiring a prior transform (e.g. log-normal) of concentrations. Cross-validation
      results show that the use of probability thresholds leads to more efficient
      delineation of contaminated areas than a classification based on the exceedence
      of regulatory thresholds by concentration estimates. Depending on whether
      additional sampling aims at reducing prediction errors or misclassification
      rates, the variance of local probability distributions or a measure of the
      expected closeness to the regulatory threshold can be used to locate candidate
      locations.

PMID- 11529568
TI  - Rapid oxidation of arsenite in a hot spring ecosystem, Yellowstone National Park.
AB  - Geothermal springs within Yellowstone National Park (YNP) often contain arsenic
      (As) at concentrations of 10-40 microM, levels that are considered toxic to many
      organisms. Arsenite (As(III)) is often the predominant valence state at the point
      of discharge but is rapidly oxidized to arsenate (As(V)) during transport in
      shallow surface water. The current study was designed to establish rates and
      possible mechanisms of As(III) oxidation and to characterize the geochemical
      environment associated with predominant microbial mats in a representative acid
      sulfate-chloride (pH 3.1) thermal (58-62 degrees C) spring in Norris Basin, YNP.
      At the spring origin, total soluble As was predominantly As(III) at
      concentrations of 33 microM. No oxidation of As(III) was detected over the first
      2.7 m downstream from the spring source, corresponding to an area dominated by a
      yellow filamentous S0-rich microbial mat However, rapid oxidation of As(III) to
      As(V) was observed between 2.7 and 5.6 m, corresponding to termination of the S0
      rich mats, decreases in dissolved sulfide, and commencement of a brown Fe/As-rich
      mat. Rates of As(II) oxidation were estimated, yielding an apparent first-order
      rate constant of 1.2 min(-1) (half-life = 0.58 min). The oxidation of As(III) was
      shown to require live organisms present just prior to and within the Fe/As-rich
      mat. Complementary analytical tools used to characterize the brown mat revealed
      an As:Fe molar ratio of 0.7 and suggested that this filamentous microbial mat
      contains iron(III) oxyhydroxide coprecipitated with As(V). Results from the
      current work are the first to provide a comprehensive characterization of
      microbially mediated As(III) oxidation and the geochemical environments
      associated with microbial mats in acid-sulfate-chloride springs of YNP.

PMID- 11529569
TI  - The absence and application of stable carbon isotopic fractionation during the
      reductive dechlorination of polychlorinated biphenyls.
AB  - A bacterial enrichment culture (specific to doubly flanked chlorine removal)
      reductively dechlorinated 2,3,4,5-tetrachlorobiphenyl (2,3,4,5-CB) to 2,3,5
      trichlorobiphenyl (2,3,5-CB) in aqueous media. Approximately 90% conversion to
      2,3,5-CB occurred after 90 days, with no other products formed. The delta13C
      values of 2,3,4,5-CB and 2,3,5-CB were relatively constant over the course of the
      reaction, indicating a very small or no isotope effect. In addition, compound
      specific delta13C analysis performed for every congener in three different lots
      of Aroclor 1268 showed an intrinsic isotopic trend of decreasing 13C abundance
      with increasing chlorine content, similar to observations in other commercial
      mixtures of polychlorinated biphenyls (PCBs). The results of this laboratory
      study suggest that microbial reductive dechlorination of PCBs in contaminated
      sediments will create congeners with more depleted delta13C values than native
      PCBs of similar chlorination. Such information may provide additional evidence
      for the occurrence of this process and aid in further understanding the
      biogeochemistry of these compounds.

PMID- 11529570
TI  - Diuron degradation in irradiated, heterogeneous iron/oxalate systems: the rate
      determining step.
AB  - The purpose of this study was to examine the various factors that control the
      kinetics of diuron degradation in irradiated, aerated suspensions containing
      goethite (alpha-FeOOH) and oxalate, in the following denoted as heterogeneous
      photo-Fenton systems. In these systems, attack by hydroxyl radicals (HO.) was the
      only pathway of diuron degradation. Studies were conducted in systems containing
      initially 80 or 200 mg L(-1) goethite (corresponding to 0.9 or 2.25 mM total
      iron) and 20, 50, 75, 100, 200, and 400 microM oxalate at 3 < or = pH < or = 6.
      Both oxalate concentration and pH greatly affected the rate of light-induced
      diuron transformation. In the presence of initial 200 microM oxalate, the rate of
      diuron degradation was maximal at pH 4, coinciding with the maximal extent of
      oxalate adsorption on the surface of goethite. At pH 4,the rate of light-induced
      diuron degradation increased with increasing oxalate concentration, reaching a
      plateau at initial 200 microM oxalate, i.e., at the oxalate solution
      concentration at which the extent of oxalate adsorption on the surface of
      goethite reached a maximum. These experimental results suggest that the rate of
      Fe(II)(aq) formation through photochemical reductive dissolution of goethite,
      with oxalate acting as electron donor, determines the kinetics of diuron
      degradation in these heterogeneous photo-Fenton systems.

PMID- 11529571
TI  - The application of 1H HR-MAS NMR spectroscopy for the study of structures and
      associations of organic components at the solid-aqueous interface of a whole
      soil.
AB  - High resolution-magic angle spinning nuclear magnetic resonance (HR-MAS NMR)
      allows the application of solution-state NMR experiments to samples that are not
      fully soluble and contain solids. Only the species in contact with the solvent
      system employed become NMR observable. In this study utilizing D2O as the solvent
      system we show it is possible to examine the structures at the solid-aqueous
      interface of a whole soil. Combining one- and two-dimensional HR-MAS NMR allowed,
      for the first time, the identification of fatty acids, aliphatic esters, and
      ethers/ alcohols as prominent species at the solid-aqueous interface of the soil
      with signals from sugars and amino acids also apparent. Few, if any signals from
      aromatic protons were observed when the soil was swollen in aqueous media,
      although these signals are observed in extracts from the same soil and when the
      soil is swollen with a more penetrating solvent(DMSO-d6)which is known to
      disassociate hydrogen bonds. These findings indicate that the soil aromatic
      moieties are protected in hydrophobic regions which are not water accessible.
      Furthermore, when the soil was amended with a herbicide (trifluralin), direct
      observations of interactions between the protons on a xenobiotic and the
      surrounding soil matrix were possible for the first time. HR-MAS promises to be a
      method that can be widely applicable to a range of complex environmental samples
      without the need for extraction, pretreatment, or purification.

PMID- 11529572
TI  - Colloid transport and deposition in water-saturated Yucca Mountain tuff as
      determined by ionic strength.
AB  - Colloid mobility and deposition were determined in model systems consisting of
      quartz sand or crushed Yucca Mountain tuff, latex microspheres (colloidal
      particles), and simulated groundwater. Ionic strength (I) was manipulated as a
      first step in defining limiting conditions for colloid transport in a system
      modeled after geochemical conditions at the Yucca Mountain site. Solutions of
      deionized water (DI), 0.1x, 1x, and 10x (the ionic strength of simulated
      groundwater) (I = 0.0116 M) were used in saturated columns under steady-state
      flow conditions. Separate experiments with conservative tracers indicated stable
      hydrodynamic conditions that were independent of I. Colloids were completely
      mobile (no deposition) in the DI and 0.1x solutions; deposition increased to 11
      13% for 1x and to 89-97% for 10x treatments with similar results for sand and
      tuff. Deposition was described as a pseudo-first-order process; however, a
      decreasing rate of deposition was apparent for colloid transport at the 10x
      condition through the tuff. A linear dependence of colloid removal (extent and
      deposition rate coefficient) on I is illustrated for the model Yucca Mountain
      system and for a glass-KCl system reported in the literature. This simple
      relationship for saturated systems may be useful for predicting deposition
      efficiencies under conditions of varying ionic strength.

PMID- 11529573
TI  - Time scales for sorption-desorption and surface precipitation of uranyl on
      goethite.
AB  - The sorption of uranium on mineral surfaces can significantly influence the fate
      and transport of uranium contamination in soils and groundwater. The rates of
      uranium adsorption and desorption on a synthetic goethite have been evaluated in
      batch experiments conducted at constant pH of 6 and ionic strength of 0.1 M.
      Adsorption and desorption reactions following the perturbation of initial states
      were complete within minutes to hours. Surface-solution exchange rates as
      measured by an isotope exchange method occur on an even shorter time scale.
      Although the uranium desorption rate was unaffected by the aging of uranium
      goethite suspensions, the aging process appears to remove a portion of adsorbed
      uranium from a readily exchangeable pool. The distinction between sorption
      control and precipitation control of the dissolved uranium concentration was also
      investigated. In heterogeneous nucleation experiments, the dissolved uranium
      concentration was ultimately controlled by the solubility of a precipitated
      uranyl oxide hydrate. The X-ray diffraction pattern of the precipitate is
      characteristic of the mineral schoepite. Precipitation is kinetically hindered at
      low degrees of supersaturation. In one experiment, metastable sorption controlled
      dissolved uranium concentrations in excess of the solubility limit for more than
      30 d.

PMID- 11529574
TI  - Mn(III) center availability as a rate controlling factor in the oxidation of
      phenol and sulfide on delta-MnO2.
AB  - Manganese oxides are involved in many environmentally important redox reactions.
      This work focuses primarily on the reaction of phenol and sulfide with delta-MnO2
      (birnessite) and the inhibitory effect of pyrophosphate on these reactions. The
      reactions were modeled in terms of Mn(III) center surface availability. The model
      partitioned the observed rate constants between two different hypothetical
      reaction pathways. One of these pathways was deemed to be dependent on Mn(III)
      center concentration, while the other was Mn(III) center independent. The
      relative contribution of each pathway was then calculated based on the
      equilibrium concentration of free Mn(III) centers at a given pyrophosphate
      concentration. Using this approach it was possible to model the observed
      pyrophosphate effects and to predict inhibition with respect to reactant
      concentration. Finally, the effects of pyrophosphate and orthophosphate on the
      reaction of sulfide and hydroquinone with delta-MnO2 were observed and compared
      to previously published observations. The observed orthophosphate and
      pyrophosphate effects were consistent with the two reaction pathway model in
      terms of Mn(III) center complexation. These findings have important implications
      for modeling and understanding the fate and transport of redox reactive material.

PMID- 11529575
TI  - Evaporation rates and vapor pressures of individual aerosol species formed in the
      atmospheric oxidation of alpha- and beta-pinene.
AB  - The semivolatile oxidation products (trans-norpinic acid, pinic acid, cis-pinonic
      acid, etc.) of the biogenic monoterpenes (alpha-pinene, beta-pinene, etc.)
      contribute to the atmospheric burden of particulate matter. Using the tandem
      differential mobility analysis (TDMA) technique evaporation rates of glutaric
      acid, trans-norpinic acid, and pinic acid particles were measured in a laminar
      flow reactor. The vapor pressure of glutaric acid was found to be log(p0
      glutaric/Pa) = - 3,510 K/T + 8.647 over the temperature range 290-300 K in good
      agreement with the values previously reported by Tao and McMurry (1989). The
      measured vapor pressure of trans-norpinic acid over the temperature range 290-312
      K is log(p0 norpinic/Pa) = - 2,196.9 K/T + 3.522, and the vapor pressure of pinic
      acid is log(p0 pinic/ Pa) = - 5,691.7 K/T + 14.73 over the temperature range 290
      323 K. The uncertainty on the reported vapor pressures is estimated to be
      approximately +/- 50%. The vapor pressure of cis-pinonic acid is estimated to be
      of the order of 7 x 10(-5) Pa at 296 K.

PMID- 11529576
TI  - Meeting data quality objectives with interval information.
AB  - Immunoassay test kits are promising technologies for measuring analytes under
      field conditions. Frequently, these field-test kits report the analyte
      concentrations as falling in an interval between minimum and maximum values. Many
      project managers use field-test kits only for screening purposes when
      characterizing waste sites because the results are presented as semiquantitative
      intervals. However, field-test kits that report results as intervals can also be
      used to make project-related decisions in compliance with false-rejection and
      false-acceptance decision error rates established during a quantitative data
      quality objective process. Sampling and analysis plans can be developed that rely
      on field-test kits to meet certain data needs of site remediation projects.

PMID- 11529578
TI  - Regeneration of perchlorate (ClO4-)-loaded anion exchange resins by a novel
      tetrachloroferrate (FeCl4-) displacement technique.
AB  - Selective ion exchange is one of the preferred treatment technologies for
      removing low levels of perchlorate (ClO4-) from contaminated water because of its
      high efficiency and minimal impact on water quality through the addition or
      removal of chemicals and nutrients. However, the exceptionally high affinity of
      ClO4- for type I anion-exchange resins makes regeneration with conventional NaCl
      brine extremely difficult and costly for practical applications. The present
      study entails the development of a novel regeneration methodology applicable to
      highly selective anion-exchange resins. Tetrachloroferrate (FeCl4-) anions,
      formed in a solution of ferric chloride and hydrochloric acid (e.g., 1 M FeCl3
      and 4 M HCl), were found to effectively displace Cl04- anions that were sorbed on
      the resin. A mass-balance analysis indicated that a nearly 100% recovery of ion
      exchange sites was achieved by washing with as little as approximately 5 bed
      volumes of the regenerant solution in a column flow-through experiment There was
      no significant deterioration of the resin's performance with respect to ClO4-
      removal after repeated loading and regeneration cycles. Thus, the new methodology
      may offer a cost-effective means to regenerate ClO4- -loaded resins with improved
      regeneration efficiency, recovery, and waste minimization in comparison with
      conventional brine regeneration techniques.

PMID- 11529577
TI  - Transport of rare earth element-tagged soil particles in response to thunderstorm
      runoff.
AB  - The downslope transport of rare earth element-tagged soil particles remobilized
      during a spring thunderstorm was studied on both a natural prairie and an
      agricultural field in southwestern Iowa (U.S.A.). A technique was developed for
      tagging natural soils with the rare earth elements Eu, Tb, and Ho to
      approximately 1,000 ppm via coprecipitation with MnO2. Tagged material was
      replaced in target locations; surficial soil samples were collected following
      precipitation and runoff; and rare earth element concentrations were determined
      by inductively coupled plasma mass spectrometry. Diffusion and exponential models
      were applied to the concentration-distance data to determine particle transport
      distances. The results indicate that the concentration-distance data are well
      described by the diffusion model, butthe exponential model does not simulate the
      rapid drop-off in concentrations near the tagged source. Using the diffusion
      model, calculated particle transport distances at all hillside locations and at
      both the cultivated and natural prairie sites were short, ranging from 3 to 73 cm
      during this single runoff event. This study successfully demonstrates a new tool
      for studying soil erosion.

PMID- 11529579
TI  - Interaction between calcium and phosphate adsorption on goethite.
AB  - Quantitatively, little is known about the ion interaction processes that are
      responsible for the binding of phosphate in soil, water, and sediment, which
      determine the bioavailability and mobility of phosphate. Studies have shown that
      metal hydroxides are often responsible for the binding of PO4 in soils and
      sediments, but the binding behavior of PO4 in these systems often differs
      significantly from adsorption studies on metal hydroxides in laboratory. The
      interaction between PO4 and Ca adsorption was studied on goethite because Ca can
      influence the PO4 adsorption equilibria. Since adsorption interactions are very
      difficult to discriminate from precipitation reactions, conditions were chosen to
      prevent precipitation of Ca-PO4 solids. Adsorption experiments of PO4 and Ca,
      individually and in combination, show a strong interaction between adsorbed Ca
      and PO4 on goethite for conditions below the saturation index of apatite. It is
      shown that it is possible to predict the adsorption and interaction of PO4 and Ca
      on electrostatic arguments using the model parameter values derived from the
      single-ion systems and without invoking ternary complex formation or
      precipitation. The model enables the prediction of the Ca-PO4 interaction for
      environmentally relevant calcium and phosphate concentrations.

PMID- 11529580
TI  - Controlling emissions from electroplating by the application of ultrasound.
AB  - Ultrasonic irradiation applied either above the surface of a chromic acid plating
      bath or through the plating bath itself during the process of chromium
      electroplating reduces the emissions of hazardous chromic acid mist The use of
      ultrasound is particularly effective at high current densities. The results
      suggest that sonication during the electroplating of chromium may provide a
      useful method of controlling chrome mist emission without the need for a chemical
      additive (mist suppressant). In conjunction with lip extraction this could lead
      to a more efficient process since the use of ultrasound has been shown to be of
      benefit in the electroplating process itself.

PMID- 11529581
TI  - In situ lifetimes and kinetics of a reductive whey barrier and an oxidative ORC
      barrier in the subsurface.
AB  - Permeable reactive barriers (PRB) are being used to engineer favorable field
      conditions for in-situ remediation efforts. Two redox adjustment barriers were
      installed to facilitate a 10-month research effort on the fate and transport of
      MTBE (methyl tert-butyl ether) at a site called the Michigan Integrated
      Remediation Technology Laboratory (MIRTL). Thirty kilograms of whey were injected
      as a slurry into an unconfined aquifer to establish an upgradient reductive zone
      to reduce O2 concentration in the vicinity of a contaminant injection source. To
      minimize the impact of contaminant release, 363 kg of oxygen release compound
      (ORC) were placed in the aquifer as a downgradient oxidative barrier. Dissolved
      oxygen and other chemical species were monitored in the field to evaluate the
      effectiveness of this technology. A transient one-dimensional advective
      dispersive-reaction (ADR) model was proposed to simulate the dissolved oxygen
      transport. The equations were solved with commonly encountered PRB initial and
      constant/variable boundary conditions. No similar previous solution was found in
      the literature. The in-situ lifetimes, based on variable source loading, were
      estimated to be 1,661 and 514 days for the whey barrier and ORC barrier,
      respectively. Estimates based on either maximum O2 consumption/production or
      measured O2 curves were found to under- or overestimate the lifetime of the
      barriers. The pseudo-first-order rate constant of whey depletion was estimated to
      be 0.303/d with a dissolution rate of 0.04/d. The oxygen release rate constant in
      the ORC barrier was estimated to be 0.03/d. This paper provides a means to design
      and predict the performance of reactive redox barriers, especially when only
      limited field data are available.

PMID- 11529582
TI  - A new hydrate-based recovery process for removing chlorinated hydrocarbons from
      aqueous solutions.
AB  - The main objective of this study was to check the feasibility of the newly
      proposed hydrate-based chlorinated hydrocarbon (CHC) recovery process for
      removing chlorinated hydrocarbons from aqueous solutions. Two key process
      variables of hydrate phase equilibria and formation kinetics were closely
      examined to develop the overall conceptual design of this technology. First, the
      ternary four-phase (H-LW-LCHC-V) hydrate equilibria of aqueous solutions
      containing methylene chloride (CH2Cl2), carbon tetrachloride (CCl4), 1,2
      dichloroethane (CH2ClCH2Cl), 1,1,1-trichloroethane (CH3CCl3), and 1,1
      dichloroethylene (CH2= CCl2) were measured at various temperature and pressure
      conditions using three different types of help gases (CO2, N2, CH4). The help gas
      + water + chlorinated hydrocarbons systems greatly reduced the hydrate-forming
      pressure, which confirmed the mixed hydrates with chlorinated hydrocarbons more
      stabilized than the simple hydrates consisting of a help gas and water. The
      degree of stabilization was found to follow the order of 1,2-dichloroethane < 1,1
      dichloroethylene < methylene chloride < 1,1,1-trichloroethane < carbon
      tetrachloride. For the N2 + water + carbon tetrachloride system, the formation
      pressure reduction as much as 96% was observed at 279.35 K. Second, the formation
      kinetic experiments of carbon dioxide hydrates containing chlorinated
      hydrocarbons were conducted under isothermal and isobaric conditions. The
      consumption rate of carbon dioxide gas became fast at the early time of the
      growth period, gradually decreased, and finally went to the complete hydration.
      The proposed hydrate-based recovery process appears to be very simple from the
      operational point of view because no special facilities requiring sensitive and
      complex function are needed. Another advantage is that this process only requires
      carbon dioxide as a hydrate former. Best of all, this process can be applied to
      separation and recovery of other organic pollutants dissolved in aqueous
      solutions without changing the basic concept.

PMID- 11529584
TI  - Antecedents to hospital deaths: all in good time.

PMID- 11529583
TI  - Recovery of sodium sulfate from farm drainage salt for use in reactive dyeing of
      cotton.
AB  - Agricultural drainage salt generated during irrigation of crops in San Joaquin
      Valley, California, exceeds 600,000 tons annually and cumulates in the field at a
      rapid rate. As a result, the waste is occupying more farmland for salt storage
      and disposal, thus causing serious concern to the environment and the local
      agricultural industry. In searching for a potential solution to reduce or
      eliminate the waste, the research describe herein explored the feasibility of
      producing a value-added product, sodium sulfate, from the waste and utilizing the
      product in textile dyeing. The results indicated that sodium sulfate could be
      produced from the salt and could be purified by a recrystalization method in a
      temperature range within the highest and lowest daily temperatures during summer
      in the valley. The recovered sodium sulfate samples, with purities ranging from
      67 to 99.91%, were compared with commercially available sodium sulfate used in
      reactive dyeing of cotton fabrics. The salt samples recovered from Mendota,
      California (>98.8% sodium sulfate), cause little color difference in the dyeing
      with selected reactive dyes. The purified salt (III) (99.91% sodium sulfate) is
      more applicable for reactive dyeing of cotton fabrics since it has no deleterious
      effect. The recovered sodium sulfate from certain areas in the valley could not
      be employed in reactive dyeing due to the high level of impurities present.

PMID- 11529585
TI  - Effects of improved glycaemic control on endothelial function in patients with
      type 2 diabetes.
AB  - BACKGROUND: Patients with type 2 diabetes have abnormal endothelial function but
      it is not certain whether improvements in glycaemic control will improve
      endothelial function. AIMS: To examine the effects of short-term improved
      glycaemic control on endothelial function in patients with inadequately regulated
      type 2 diabetes mellitus. METHODS: Forty-three patients with type 2 diabetes and
      glycosylated haemoglobin (HbA1c) > 8.9% were randomized to either improved
      glycaemic control (IC) n = 21 or usual glycaemic control (UC) n = 22 for 20
      weeks. Using high-resolution B-mode ultrasound, brachial artery flow-mediated
      dilatation (FMD) and glyceryl trinitrate-mediated dilatation (GTN-D) were
      measured at baseline and 20 weeks later. RESULTS: After 20 weeks, HbA1c was
      significantly lower in IC versus UC (IC 8.02 +/- 0.25% versus UC 10.23 +/- 0.23%,
      P < 0.0001) but changes in FMD and GTN-D were not different between the groups
      (FMD at baseline and week 20 IC 5.1 +/- 0.56% versus 4.9 +/- 0.56% and UC 4.2 +/-
      0.51% versus 3.1 +/- 0.51%; P = 0.23: GTN-D IC 12.8 +/- 1.34% versus 10.4 +/-
      1.32% and UC 13.7 +/- 1.2% versus 12.7 +/- 1.23%; P = 0.39). In the IC group
      weight increased by 3.2 +/- 0.8 kg after 20 weeks compared to 0.02 +/- 0.70 kg in
      UC (P = 0.003). Blood pressure and serum lipid concentrations did not change in
      either group. CONCLUSIONS: Short-term reduction of HbA1c levels did not appear to
      affect endothelial function in patients with type 2 diabetes and previously
      poorly regulated glycaemic control.

PMID- 11529586
TI  - Outcomes in the management of atrial fibrillation: clinical trial results can
      apply in practice.
AB  - BACKGROUND: The benefits of antithrombotic therapy in chronic atrial fibrillation
      (AF) have been established in clinical trials, but there is a paucity of data on
      outcomes in practice. AIMS: The objective was to establish a large ongoing
      database of patients with non-valvular AF, to enable the accurate determination
      of clinical outcomes. METHODS: A retrospective review of the medical records for
      consecutive patients who had AF documented on electrocardiogram at the major
      teaching hospital in Tasmania between 1 January 1997 and 30 June 1999 was
      performed. An extensive range of demographic and clinical variables was recorded
      for all patients with chronic or paroxysmal non-valvular AF. RESULTS: The 505
      patients (60% males) included in the database had a median age of 76 years.
      According to risk stratification criteria, 79% of the patients with previously
      diagnosed chronic or paroxysmal AF had a high risk of developing stroke at the
      time of admission to hospital care. However, only one-third (34%) of these
      patients were receiving warfarin (or warfarin plus aspirin), with almost one
      quarter (24%) receiving no antithrombotic agent. The annual incidence of
      ischaemic strokes was 3.4% (1.5-6.4%; 95% CI) when taking warfarin, compared to
      7.0% (5.2-9.4%) for patients not taking warfarin and 7.8% (5.4-11.1%) for
      patients taking aspirin. The annual incidence of bleeding complications in
      patients taking warfarin was 14.2% (10.0-19.5%) overall and 3.4% (1.5-6.4%) for
      major bleeds. In patients not taking warfarin, the overall annual incidence of
      bleeds was 8.4% (6.3-10.9%) and 3.9% (2.5-5.7%) for major bleeds. CONCLUSIONS:
      Warfarin is underused in patients with AF. In clinical practice, warfarin confers
      a similar stroke risk reduction to that observed in trials, with an increase in
      incidence of only minor bleeding complications. Aspirin did not appear to reduce
      the risk of stroke.

PMID- 11529587
TI  - Single institution outcomes of treatment of severe aplastic anaemia.
AB  - BACKGROUND: In severe aplastic anaemia, the treatment of choice for young
      patients with a human leucocyte antigen-matched sibling is now established as
      allogeneic bone marrow transplantation (BMT). In older patients and in those
      without a matched sibling donor, immunosuppressive therapy is the usual first
      option. 'Alternative' marrow donors are emerging as an option for those without a
      matched sibling donor. AIMS: To review 10 years of local experience in treating
      severe aplastic anaemia with BMT and immunosuppressive therapy with emphasis on
      long-term outcomes. METHODS: A retrospective analysis was performed of all
      patients with severe aplastic anaemia presenting to the Royal Brisbane and Royal
      Children's Hospitals between 1989 and 1999. Data were abstracted regarding
      patient demographics, pretreatment characteristics and outcome measures,
      including response rates, overall survival and long-term complications. RESULTS:
      Twenty-seven consecutive patients were identified, 12 treated with
      immunosuppression alone and 15 with BMT. In these two groups, transfusion
      independence was attained in 25% and 100%, respectively, with overall survival
      being 36% and 100%, respectively. Those treated with immunosuppression were
      significantly older (median 41.5 versus 22 years, P = 0.008). Long-term survivors
      of either treatment had extremely low morbidity. Three patients carried
      pregnancies to term post-transplant. Three patients received alternative donor
      BMT with correspondingly excellent survival. CONCLUSIONS: Patients treated with
      allogeneic BMT for severe aplastic anaemia enjoyed extremely good long-term
      survival and minimal morbidity. Patients treated with immunosuppressive therapy
      had a poorer outcome reflecting their older age and different usage of therapies
      over the past decade. Optimal treatment strategies for severe aplastic anaemia
      remain to be determined.

PMID- 11529589
TI  - Current perspectives on BRCA1- and BRCA2-associated breast cancers.
AB  - The identification of two breast cancer predisposition genes, BRCA1 and BRCA2, in
      the mid-1990s has led to a better understanding of the molecular pathogenesis of
      hereditary breast cancer and to a new era in breast cancer research. The present
      article reviews the current state of knowledge regarding the biology of BRCA1 and
      BRCA2, the cancer risks associated with carrying a pathogenic mutation in either
      of these genes and the possible genetic and environmental risk modifiers. The
      phenotypes of BRCA1- and BRCA2-associated hereditary breast cancers are reviewed.
      Research into BRCA1- and BRCA2-associated breast cancer is in its infancy and
      much remains to be learned, particularly about modifiers of genetic risk and the
      clinical implications of carrying a mutation in one of these two genes. Australia
      has an excellent research infrastructure in place, through the Australian Breast
      Cancer Family Study and the Kathleen Cuningham Foundation Consortium for Research
      into Familial Breast Cancer, to contribute substantially to future research in
      this area.

PMID- 11529588
TI  - Antecedents to hospital deaths.
AB  - BACKGROUND: Recent studies have suggested there are a large number of potentially
      preventable deaths in Australian hospitals. AIM: This study aimed to document
      antecedent factors in hospital deaths in an attempt to identify potentially
      preventative factors. METHODS: The study was conducted at three separate acute
      hospitals. Demographics of all deaths were recorded over a 6-month period as well
      as antecedent factors present within 0-8 and 8-48 h of all deaths including vital
      sign abnormalities, cardiorespiratory arrests and admission to intensive care.
      Separate analysis was performed on 'not for resuscitation' deaths. RESULTS: There
      were a total of 778 deaths, of which 549 (71%) were 'not for resuscitation'.
      There were 171 (22%) deaths preceded by arrest and 160 (21%) preceded by
      admission to intensive care. Of the remaining deaths, 30% had severely abnormal
      physiological abnormalities documented. This incidence was 50% in the non-do not
      resuscitate (DNR) subgroup. Concern about the patient's condition was expressed
      in the patient's notes by attending nursing staff and junior medical staff in
      approximately one-third of non-DNR deaths. Hypotension (30%) and tachypnoea (17%)
      were the most common antecedents in the non-DNR deaths. CONCLUSION: There is a
      high incidence of serious vital sign abnormalities in the period before
      potentially preventable hospital deaths. These antecedents may identify patients
      who would benefit from earlier intervention.

PMID- 11529590
TI  - The oratory of addiction: a 30-year perspective on alcohol and drug misuse.
AB  - The annual Leonard Ball Orations illustrate changing perspectives in Australia
      over 30 years on medical and social effects of misuse of alcohol and other
      substances. The first oration, in 1968, examined causal factors in the context of
      'agent', 'purveyor' and 'host' and provided themes for subsequent orators. In
      regard to the agent (alcohol), it was proposed that availability (and cost)
      determined not only overall consumption within the community, but also numbers of
      users at hazardous levels. This principle seemed applicable to substance misuse
      and addictive behaviours overall. The influence of purveyors (and advertisers)
      was discussed with expectedly different perspectives from the liquor industry and
      social and health-care providers. The role of host was examined in terms of
      genetic predisposition, foreshadowing current experimental applications of gene
      transfer and disruption technologies in mice to substance misuse and the promise
      of the Human Genome Project in clarifying inheritance of substance misuse.
      Individual successes in harm reduction were described in the context of alcohol
      and road trauma, smoking prevention and heroin addiction. Government intervention
      was introduced with the 1987 National Campaign Against Drug Abuse. The focus
      shifted during the 1980s from alcohol to addictive drugs, in line with community
      concerns. The 1996 oration on the aborted Canberra trial of supervised heroin
      administration illustrated the need for, and problems associated with, such
      studies. The prescience and achievements of the Ball orators provide optimism and
      direction for efforts in the future.

PMID- 11529591
TI  - Salmonella prosthetic valve (mechanical) endocarditis managed conservatively.

PMID- 11529592
TI  - Azathioprine hypersensitivity mimicking underlying inflammatory bowel disease.

PMID- 11529593
TI  - Hypoglycaemia and electrocardiographic changes in a subject with diabetes
      mellitus.

PMID- 11529594
TI  - Response to erythropoietin in chronic myelomonocytic leukaemia.

PMID- 11529595
TI  - Diltiazem-mediated inhibition of sildenafil metabolism may promote nitrate
      induced hypotension.

PMID- 11529596
TI  - Diltiazem-mediated inhibition of sildenafil metabolism may promote nitrate
      induced hypotension.

PMID- 11529597
TI  - Cost-effectiveness and accuracy of exercise stress echocardiography in the non
      invasive diagnosis of coronary heart disease.

PMID- 11529598
TI  - Who is responsible for measuring nursing outcomes?

PMID- 11529599
TI  - Infant behaviors as indicators of established acute pain.
AB  - ISSUES AND PURPOSE: Many infant pain assessment tools use infant behaviors
      indicative of increased arousal. These tools were developed and tested using
      clinical situations involving acute immediate pain responses. Are these behaviors
      valid, clinical indicators of acute established pain (non-procedurally caused)
      pain? Can these tools be used to assess acute established infant pain? This
      article explores research findings to answer these questions. CONCLUSIONS:
      Findings suggest that behaviors indicative of increased arousal (e.g., crying,
      facial expressions that accompany crying) are nonspecific indicators of distress
      rather than independent indicators of established acute pain. Thus, the use of
      behaviors representing acute immediate pain responses to assess acute established
      pain, or the use of tools that incorporate these behaviors, can be misleading.
      PRACTICE IMPLICATIONS: Always use acute immediate pain behavioral responses
      (behaviors indicative of increased arousal) in conjunction with clinical data
      concerning "likelihood of pain" and consolability.

PMID- 11529600
TI  - Spirituality in African-American mothers coping with a seriously ill infant.
AB  - ISSUES AND PURPOSE: To describe how African-American mothers' spirituality helped
      them cope during the time of their infants' hospitalization for a serious
      illness. DESIGN AND METHODS: Fourteen mothers whose infants were seriously ill in
      the early months of life were interviewed for this retrospective, descriptive
      study. RESULTS: The core theme related to prayer. Four mothers reported a
      strengthened faith, while two mothers continued to have difficulty relating to
      God or attending church. PRACTICE IMPLICATIONS: These findings support the
      importance of understanding and respecting the spiritual needs and expressions of
      spirituality in African-American mothers who are coping with a serious illness in
      one of their children.

PMID- 11529601
TI  - Predicting the distance for nasojejunal tube insertion in children.
AB  - ISSUES AND PURPOSE: As no consistent predictor of insertion tube distance has
      been determined for intestinal feeding tubes and fluoroscopic placement is very
      expensive, this study sought a reliable method of blind placement. DESIGN AND
      METHODS: This cross-sectional study measured the internal distance from the lip
      to the pylorus in 387 children undergoing upper gastrointestinal endoscopy and
      compared those measurements to the external distances measured from the nose
      around the ear to the 10th rib and lip around the ear to the 10th rib. RESULTS:
      Regression equations using height fitted in four age groups were the best
      predictors of the internal pyloric distances. PRACTICE IMPLICATIONS: Predicting
      this distance with height may help healthcare providers be more successful in
      blind placement of intestinal feeding tubes. A table of predicted nasointestinal
      tube insertion distances is included.

PMID- 11529602
TI  - Pediatric nurses: advocates against youth violence.
AB  - ISSUES AND PURPOSE: This article examines the issues of youth violence and the
      role of the pediatric nurse in addressing youth at risk for violence. An example
      of a school-based violence prevention program is included. CONCLUSIONS: Black
      adolescent males from lower socioeconomic backgrounds and violent communities
      tend to be at highest risk. However, the profile of risk for violence is
      expanding to include youth in rural and middle-class suburban settings. PRACTICE
      IMPLICATIONS: Pediatric nurses play a vital role in the identification of at-risk
      youth and in the planning and evaluation of interventions for youth violence
      prevention.

PMID- 11529603
TI  - Ask the expert: vaccine safety communication: the role of the pediatric nurse.

PMID- 11529604
TI  - Role play: mentoring, membership in professional organizations, and the pursuit
      of excellence in nursing.
AB  - It is our professional responsibility to encourage membership in nursing
      organizations. Membership helps nurses make intelligent, well-informed decisions
      about health care and our profession. It also enhances our credibility and helps
      validate nursing as a profession. Plato said, "Those having torches will pass
      them on to others." As nurses, educators, preceptors, advocates and mentors, we
      carry the fire.

PMID- 11529605
TI  - Scientific inquiry: an introduction to search engines.

PMID- 11529606
TI  - Small area population disease burden.
AB  - Small area health statistics has assumed increasing importance as the focus of
      population and public health moves to a more individualised approach of smaller
      area populations. Small populations and low event occurrence produce difficulties
      in interpretation and require appropriate statistical methods, including for age
      adjustment. There are also statistical questions related to multiple comparisons.
      Privacy and confidentiality issues include the possibility of revealing
      information on individuals or health care providers by fine cross-tabulations.
      Interpretation of small area population differences in health status requires
      consideration of migrant and Indigenous composition, socioeconomic status and
      rural-urban geography before assessment of the effects of physical environmental
      exposure and services and interventions. Burden of disease studies produce a
      single measure for morbidity and mortality--disability adjusted life year (DALY)-
      which is the sum of the years of life lost (YLL) from premature mortality and the
      years lived with disability (YLD) for particular diseases (or all conditions).
      Calculation of YLD requires estimates of disease incidence (and complications)
      and duration, and weighting by severity. These procedures often mean problematic
      assumptions, as does future discounting and age weighting of both YLL and YLD.
      Evaluation of the Victorian small area population disease burden study presents
      important cross-disciplinary challenges as it relies heavily on synthetic
      approaches of demography and economics rather than on the empirical methods of
      epidemiology. Both empirical and synthetic methods are used to compute small area
      mortality and morbidity, disease burden, and then attribution to risk factors.
      Readers need to examine the methodology and assumptions carefully before
      accepting the results.

PMID- 11529607
TI  - Are qualitative methods misunderstood?
AB  - Qualitative research methods are increasingly utilised by health researchers.
      Along with this the criteria for assessing the quality of qualitative research
      are changing from a natural science model to an interpretative social science
      model. This is a product of the realisation by health researchers that
      qualitative methods utilise a different epistemology to statistical methods. I
      demonstrate that a recent article in the Australian and New Zealand Journal of
      Public Health draws on a now outdated natural science methodology of assessing
      bias in focus groups. Drawing on interpretativist social science theory and
      recent work in the British Medical Joumal I argue for the importance of examining
      the social contexts through which qualitative data is produced.

PMID- 11529608
TI  - Asking the right questions of disadvantaged and homeless communities: the role of
      housing, patterns of illness and reporting behaviours in the measurement of
      health status.
AB  - OBJECTIVE: To assess the self-reported health status and its relationship to key
      demographic variables among patrons of a charity-run meals service at The Exodus
      Foundation, in urban Sydney, Australia. METHOD: Random-sample cross-sectional
      study of 100 face-to-face interviews (79% recruitment rate). Self-reported health
      status was measured by subjective rating scale, open-ended and checklist
      questions about presence and type of acute and chronic disease. Anaysis by
      logistic regression of fair-poor health status on demographic variables in Exodus
      patrons and genera Sydney population adjusted for age and sex using the 1995
      National Health Survey. RESULTS: Compared to housed but poor counterparts within
      the Exodus sample, homeless people were significantly more likely to report fair
      poor health status (age-adjusted OR-3.0, 95% CI 1.3-7.1). Exodus patrons, as a
      whole, were much more likely than Sydney's general population to report fair-poor
      health status, after adjusting for age and sex (OR-4.5, 95% CI 2.9-7.0) and had a
      more serious pattern of illness (diseases of the digestive system; depression;
      common cold; bronchitis; refractive errors; drug and alcohol dependence; diabetes
      mellitus Type II). Exodus patrons reported fewer acute and chronic illnesses with
      open-ended questions than with a checklist (p<0.001). CONCLUSION: In this
      population there was a strong relationship between poor health and homelessness.
      When patterns of illness and injury were measured within this disadvantaged
      group, they showed more serious illness types than in the general population.
      Such patterns may not be identified by methods often used in traditional
      population health surveys.

PMID- 11529609
TI  - Into a SEIFA SES cul-de-sac?
AB  - Use of the Australian Bureau of Statistics' SEIFA scores has almost become an
      automatic practice in area-based research on socio-economic status (SES)
      correlates of health inequalities in Australia in recent years. This article
      questions the wisdom of this emerging heavy, often singular, reliance on the
      SEIFA indexes for representing a real socio-economic condition. It is argued that
      improvements in our understanding of the social and economic processes that
      produce health inequalities will not occur unless we move beyond SEIFA's broad
      brush. Data for New England Area Health local government areas are used to
      support the argument.

PMID- 11529610
TI  - Farm-related fatalities involving children in Australia, 1989-92.
AB  - OBJECTIVE: To describe the types of and circumstances surrounding unintentional
      farm-related fatal injuries involving children aged less than 15 years in
      Australia. METHODS: Information concerning 115 deaths were obtained from
      inspection of coronial files for the period 1989-92. RESULTS: Children less than
      15 years made up 20% of all unintentional farm-related fatalities in Australia,
      with children less than 5 years representing 63% of all child fatalities. The
      majority of children were fatally injured while bystanders to farm work and
      equipment used on the farm (including dams), with drowning the most common
      mechanism of the fatal incident for children aged both 5 years or less and 5-9
      years. Vehicle accidents were common for children aged 10-14 years. CONCLUSIONS:
      Children are exposed to various hazards in the farming environment and as such
      are at risk of being injured. IMPLICATIONS: This study has highlighted a number
      of particular hazards for children on farms, with drowning, transport and tractor
      related injuries of particular concern. A national strategy for child safety on
      farms has been developed by Farmsafe Australia aimed at providing a nationally co
      ordinated plan for improving child safety on farms.

PMID- 11529611
TI  - Suicide prevention in Aboriginal communities: application of community gatekeeper
      training.
AB  - OBJECTIVE: Concern over the high rate of suicide among Aboriginal people on the
      south coast of NSW led to the development of a project aimed at preventing youth
      suicide in the Aboriginal communities of the Shoalhaven. This paper describes the
      development, implementation and evaluation of the project. METHOD: Following
      extensive consultation with the Aboriginal community, a range of culturally
      appropriate interventions were developed. The main focus was a series of
      community gatekeeper training workshops, which aimed to increase the potential of
      members of the Aboriginal community to identify and support people at risk of
      suicide and to facilitate their access to helping services. RESULTS: Evaluation
      of the workshops demonstrated an increase in participants' knowledge about
      suicide, greater confidence in identification of people who are suicidal, and
      high levels of intentions to provide help. Attitudes, subjective norms and
      barriers predicted intentions to help. CONCLUSIONS: The project indicated
      community members could be successfully trained in the recognition of individuals
      at risk of suicidal behaviour. Gatekeepers' attitudes and perceived barriers to
      helping predicted intentions to help those in need. There is a need for longer
      term follow-up to assess the extent to which new knowledge and skills are used in
      practice. IMPLICATIONS: Suicide awareness and skills training have been
      demonstrated to be an effective early intervention strategy. Gatekeeper training
      empowers Aboriginal communities and is generally accepted. There is demand for
      such programs outside the Shoalhaven. The project has a methodological framework
      that can be easily adapted by other communities.

PMID- 11529612
TI  - Social disadvantage and variation in the incidence of end-stage renal disease in
      Australian capital cities.
AB  - OBJECTIVE: To evaluate variation in the incidence of end-stage renal disease
      (ESRD) within Australian capital cities. To explore the relation between the
      incidence of ESRD and socioeconomic disadvantage. METHODS: We obtained data from
      the Australian and New Zealand Dialysis and Transplant Registry (ANZDATA)
      regarding 5,013 patients from capital cities who started ESRD treatment between 1
      April 1993 and 31 December 1998. We used the postcode at the start of treatment
      to calculate the average annual incidence of ESRD for each of 51 capital city
      regions using 1996 Census counts based on place of usual residence. We calculated
      standardised incidence ratios with 95% confidence intervals for each region. The
      standardised incidence ratios were examined in relation to the SEIFA Index of
      Relative Socio-economic Disadvantage (IRSD), derived from the 1996 Census. Low
      IRSD values indicate more disadvantaged areas. RESULTS: There is significant
      variation in the standardised incidence of ESRD within capital cities. There was
      a significant correlation (r=-0.41, p=0.003) between the standardised incidence
      ratio for ESRD and the SEIFA IRSD. CONCLUSIONS AND IMPLICATIONS: Capital city
      areas that are more disadvantaged have a higher incidence of ESRD. Socioeconomic
      factors may be important determinants of the risk of developing ESRD.

PMID- 11529613
TI  - A comparison of the prevalence of respiratory illness and non-specific health
      symptoms in two Victorian cities.
AB  - OBJECTIVE: To compare the prevalence of respiratory illness and non-specific
      health symptoms among adults and children aged 4-15 years living in Portland and
      Warrnambool, Victoria. METHODS: A postal survey of 3,903 adults in Portland and
      Warrnambool systematically selected from the electoral roll was undertaken. Both
      an adults and children's questionnaire were enclosed in the mailing to each
      adult. If there were children aged 4-15 years in the household, an adult was
      asked to complete a questionnaire for the child who would next celebrate a
      birthday. Questionnaires were returned by 2,111 adults (54%) and for 585
      children. RESULTS: No significant differences in the prevalence of self-reported
      asthma or wheeze were observed among adults or children residing in Portland and
      Warrnambool. The likelihood of itchy eyes, skin rash and stuffy nose was
      significantly higher in Portland adults and children compared with those in
      Warrnambool. Dry cough at night was increased among Portland children, but not
      significantly so. CONCLUSIONS: Higher rates of non-specific symptoms were
      observed in Portland but from a cross-sectional survey such as this, it is not
      possible to identify the cause of these higher rates. They may be related to
      environmental factors such as pollens or emissions from aluminium production,
      fertiliser production or bulk handling activities on the wharf, or they may be
      attributable to other factors such as response or recall bias.

PMID- 11529614
TI  - Predictors of early rescreening in the National Cervical Screening Program,
      Australia.
AB  - OBJECTIVE: To identify variables that predict early rescreening after a negative
      Pap smear report. METHODS: Cohort study using the records of a statewide Cervical
      Cytology Registry in Victoria, Australia. The cohort comprised 31,082 women who
      had a negative Pap smear report during the first half of 1996 and who were
      rescreened within the subsequent 36 months. Early rescreening was defined as a
      further Pap smear within 21 months. RESULTS: The strongest predictor of early
      rescreening was a recommendation at the time of issuing the negative Pap smear
      report by the laboratory for retesting before two years (adjusted odds ratio =
      3.81, 95% confidence interval (CI) 3.58-4.05). Mention of reactive or
      inflammatory change as part of the negative Pap smear report was also a powerful
      predictor (adjusted odds ratio = 1.67, 95% CI 1.50-1.85). Significant predictors
      associated with the women were young age, high socio-economic status and
      residence in the capital city. Significant predictors associated with the
      practitioner were if either the index or subsequent smear was collected by an
      obstetrician/ gynaecologist or a hospital-based clinic, or if the practitioner
      collecting the index smear was a female. The population-attributable risk per
      cent associated with the laboratory recommendation was 27%. CONCLUSIONS: This
      data suggests that a multifaceted strategy targeting pathology laboratories,
      practitioners and women may be needed to reduce early rescreening. IMPLICATIONS:
      Early rescreening is wasteful of health resources. New screening programs should
      be designed to avoid this problem.

PMID- 11529615
TI  - Factors associated with smoke-free homes in NSW: results from the 1998 NSW Health
      Survey.
AB  - OBJECTIVE: To examine the sociodemographic characteristics associated with smoke
      free homes (SFHs) in NSW and specify high-risk groups with a low prevalence of
      household smoking restrictions. METHODS: Data were drawn from the 1998 NSW Health
      Survey, a computer-assisted telephone interview survey of 17,494 randomly
      selected respondents aged > or = 16 years across NSW (response rate = 70%).
      Logistic regression analyses, stratified by smoking status, were used. RESULTS:
      Overall, 72% of adults reported having a SFH; 87% of never-smokers, 81% of ex-
      and 35% of current smokers. The highest percentages of SFHs were reported in
      households with young children (78%) and with older children (72%) or with adults
      only (72%). For smokers, SFHs were independently associated with the presence of
      young children (OR=3.8, 95% CI 3.1-4.7) compared with those who lived alone, but
      the odds of living in a SFH were only slightly increased for smokers living with
      older children (aged 6-15) and for those living with adults only (OR=1.9, OR=1.8
      respectively). Speaking a language other than English at home, having more than
      10 years' education, and being <35 years old were independently and positively
      associated with SFH. Being employed in smoke-free workplaces increased the
      likelihood of SFHs for both current and past smokers (OR=1.6, OR=1.2
      respectively). CONCLUSION: Most NSW homes have restrictions on smoking inside,
      but more than half the households with children and at least one smoker adult are
      not smoke free. IMPLICATIONS: Interventions to shape parents' smoking behaviour
      around older children are warranted. Strategies need to address never-smokers in
      communities with high prevalence of smoking and adults with lower levels of
      education. A continued commitment to workplace smoking bans is important as they
      may affect household smoking restrictions.

PMID- 11529616
TI  - Fluoridation--what the public know and what they want.
AB  - OBJECTIVE: To describe the knowledge and beliefs on fluoridation of a community
      served by an unfluoridated water supply prior to consultation on implementing
      fluoridation. METHODS: Telephone survey of a sample of residents and businesses
      utilising semi-structured questionnaires. Comparisons were made among responses
      of ethnic and age groups. RESULTS: Residents were more conversant concerning
      fluoridation than business users. Knowledge and beliefs among ethnic groups
      differed significantly. Younger persons and those who had never been married were
      less knowledgeable. Pamphlets supplied by water-provider organisations or health
      professionals were the preferred methods of acquiring fluoridation information.
      The majority of respondents wished the opportunity to express their views via a
      referendum. Health authorities were the favoured decision-makers. CONCLUSIONS AND
      IMPLICATIONS: Gaps were identified in this community's knowledge on fluoridation
      with important differences based on ethnicity and age. Strategies to inform the
      public on water fluoridation need to address these subgroup differences.

PMID- 11529617
TI  - A model of therapeutic intervention with Indigenous Australians.
AB  - Many non-Aboriginal mental health practitioners are confronted by the lack of
      practical information pertaining to interventions with Aboriginal clientele.
      Subsequently, this may have engendered uncertainty in potential therapists and
      counsellors due to the lack of reliable, practical and culturally appropriate
      information. Those non-Aboriginal mental health practitioners working in the
      field with Aboriginal clients do so with varying degrees of success and build
      upon their knowledge base through personal experience and anecdotal information.
      Unfortunately, this information is often not made available to others working in
      the field through journal publication. This Practice Note examines a model of
      intervention aimed at developing relationships to enhance therapeutic
      interventions at the individual, family and systems level. As a way of
      clarification, the model is described via a case study involving a psychological
      intervention with a remote Aboriginal community.

PMID- 11529618
TI  - Sunburn and sun protection among New Zealand adolescents over a summer weekend.
AB  - OBJECTIVE: To examine predictors of sunburn and sun protection practices during
      summer weekends within a sample of NZ adolescents. METHOD: Phone interviews were
      conducted with 203 participants aged 12-17 years. Questions were asked about
      behaviour from 11am to 4pm during the previous weekend. RESULTS: Less than half
      of the sample outside during peak radiation hours wore sunscreen and only a
      quarter wore hats. Sunburn was experienced by 31% of adolescents and was
      associated with spending longer times outside and use of sunscreen without
      reapplication. Wearing a sunhat was predicted by being younger and male, while
      sunscreen use was predicted by being female. CONCLUSIONS: There is a lack of
      appropriate sun protection among many NZ adolescents, and correspondingly high
      rates of sunburn. Possible opportunities to address this are through increasing
      the efficacy of sunscreen and sun hat use, and creating outdoor environments that
      support sun avoidance.

PMID- 11529619
TI  - Quality of life in HCV-infection: lack of association with ALT levels.
AB  - OBJECTIVES: To examine the impact of HCV infection in an Australian clinic
      population and identify the relationships between morbidity, psychosocial
      variables and one clinical indicator of HCV activity, alanine aminotransferase
      (ALT). METHOD: Ninety-five untreated HCV-infected patients (21-69 years) in
      infectious and liver diseases clinics who were all positive for HCV-RNA and had
      no significant comorbidities or coinfections completed a survey containing the
      Short Form 36 (SF36), as well as the six-item Social Support Questionnaire
      (SSQ6), demographic items and questions concerning respondents' perceptions of
      their mode and duration of infection. Nine volunteers from this group
      participated in semi-structured qualitative interviews aimed at exploring the
      social impact of HCV status. These data were compared with serum ALT levels. SF36
      scores were compared to population norms and according to participant variables.
      RESULTS: Mean SF36 scores were significantly lower, across all modalities, than
      population norms. SF36 scores differed significantly according to age, sex, mode
      of infection, alcohol and methadone use, and satisfaction with social support.
      They did not differ significantly according to perceived or actual ALT level or
      pattern of ALT activity. Worry about ALT was prevalent (>50%) and this was
      independent of perceived ALT level. CONCLUSIONS AND IMPLICATIONS: HCV-infection
      is associated with significantly reduced quality of life and includes the
      perception of substantial social discrimination. ALT levels are of limited
      usefulness in ascertainment of a person's sense of wellbeing and quality of life
      in HCV-infection. Increased support and information for affected individuals and
      measures aimed at countering social discrimination are important recommendations
      of the current study.

PMID- 11529620
TI  - Abattoir-associated Q fever: a Q fever outbreak during a Q fever vaccination
      program.
AB  - OBJECTIVES: To investigate an abattoir outbreak of Q fever in southem New South
      Wales with reference to the protective effect and safety of the formalin
      inactivated Q fever vaccine (Q Vax) administered before and during the outbreak.
      METHODS: In September 1998, after notification of four Q fever cases in the
      abattoir, a cohort investigation of 103 workers was undertaken. Data on age, sex,
      immune status, vaccination status and main work area were obtained from the
      medical officer administering the vaccination program and abattoir records.
      Symptoms and occupational risk factors for illness were obtained from interview
      of 63 (61%) employees. RESULTS: Of 103 abattoir employees, 16 (16%) had immunity
      from previous Q fever exposure and 19 (18 %) had been vaccinated at least six
      weeks before the first case of Q fever exposure in the abattoir. Of the remaining
      68 workers who were susceptible to primary infection, 29 (43%) had laboratory
      confirmed acute primary Q fever and eight were suspected cases. No workers
      vaccinated before the likely period of exposure developed Q fever. Of 32 workers
      vaccinated post-exposure, four developed laboratory-confirmed Q fever within
      eight days of vaccination. Vaccination administered 10 or more days after the
      likely period of exposure showed no significant protective effect (RR=0.57; 95%
      CI 0.13-2.57; p=0.60). CONCLUSIONS: Q-Vax was highly effective when administered
      in advance of the likely period of Q fever exposure. Post exposure vaccination
      was not shown to be protective. IMPLICATIONS: This study reinforces meat industry
      vaccination guidelines for abattoir employees. The optimal time to vaccinate
      workers is before they are put at occupational risk.

PMID- 11529621
TI  - C. trachomatis and N. gonorrhoeae surveillance in New Zealand: comparison of
      laboratory and clinic data.
AB  - OBJECTIVE: To determine the extent to which clinic-based sexually transmitted
      infection (STI) surveillance underrepresents the number of laboratory-confirmed
      cases of Chlamydia trachomatis and Neisseria gonorrhoeae in the Waikato and Bay
      of Plenty regions of New Zealand; and to estimate incidence rates for these two
      infections. METHODS: Data on C. trachomatis and N. gonorrhoeae were collected
      from diagnostic laboratories in the study regions for the year 2000, and compared
      with routine clinic-based STI surveillance data. RESULTS: Most laboratory
      confirmed C. trachomatis (65.5%) and N. gonorrhoeae (55.7%) infections were
      diagnosed by healthcare providers outside the clinic-based STI surveillance
      system. The estimated incidence rate for C. trachomatis was 501 per 100,000, and
      50 per 100,000 for N. gonorrhoeae. CONCLUSIONS AND IMPLICATIONS: Laboratory
      surveillance of C. trachomatis and N. gonorrhoeae provides a more complete
      picture of disease burden. Given the high infection rates reported, developing a
      national strategy for the management of STIs should be a public health priority
      in New Zealand.

PMID- 11529622
TI  - Health and safety issues pertaining to genetically modified foods.
AB  - Genetic modification involves the insertion of genes from other organisms (within
      or between species) into host cells to select for desirable qualities. Potential
      benefits of GM foods include increased nutritional value; reduced allergenicity;
      pest and disease-resistance; and enhanced processing value. Possible detrimental
      outcomes include producing foods with novel toxins, allergens or reduced
      nutritional value, and development of antibiotic resistance or herbicide
      resistant weeds. Benefits to individuals or populations need to be weighed
      against adverse health and environmental risks, and may differ between developing
      and Westernised countries. Whether testing and monitoring should exceed
      requirements for conventional foods is under debate. While not necessarily
      scientifically justifiable, consumer concerns have resulted in Australian and New
      Zealand requirements to label foods containing GM-produced proteins. Dissatisfied
      consumer advocacy groups are calling for all foods involving GM technology to be
      labelled, irrelevant of whether the final product contains novel protein. Goals
      to improve the quantity, quality and safety of foods are laudable; however, the
      primary aim of the bio-food industry is financial gain. GM foods may be as safe
      as conventional foods but public distrust runs high. It is important that
      discussion is informed by science and that claims of both benefits and risks are
      evidence-based, to ensure that the process is driven neither by the vested
      interest of the bio-technical multinational companies on the one hand, nor ill
      informed public fears on the other.

PMID- 11529623
TI  - Introducing ICD-10 into psychiatric coding practice: a WA experience.

PMID- 11529624
TI  - Corporate affiliation bias and BAe 146 aircraft: Senate report.

PMID- 11529625
TI  - Maori health services, Maori conceptions of health and cultural assimilation.

PMID- 11529626
TI  - In defence of the Australian Childhood Immunisation Register.

PMID- 11529627
TI  - Patients with systemic vasculitis: plea for their inclusion into large
      multicentre trials.

PMID- 11529628
TI  - Malignancy in Behcet's disease: a report of 13 cases and a review of the
      literature.
AB  - Behcet's disease (BD) has rarely been reported in association with malignant
      diseases. In most cases the autoimmune nature of the disease itself or
      immunosuppressive drug use has been blamed for malignant transformation. We
      report 13 cases of BD concurrent with neoplastic disease as well as treatment
      related morbidities in this particular patient group. Between 1986 and 1999, 400
      patients were diagnosed as having BD in Hacettepe University Hospitals. Of these
      13 patients, 3.25% developed malignant diseases within a median follow-up time of
      9.8 years. Solid tumors were diagnosed in 10 patients and haematological or
      lymphoid malignancies in three. Surgery was performed in seven patients, whereas
      radiotherapy was applied in six and chemotherapy in eight. A literature review
      revealed 27 cases of BD associated with malignancies, mostly lymphoid or
      haematological. Ten of our cases were solid tumors, and to our knowledge most of
      these are the first reported cases of specific malignancies concurrent with BD.
      Treatment-related morbidities were wound infection as surgical morbidity in one
      patient (1/7) and radiotherapy-related morbidity in three (3/6) patients in a
      median follow-up time of 2 years. Solid tumors in addition to lymphoid and
      haematological malignancies are also seen during the course of BD. Radiation
      therapy may cause severe late toxicities in the presence of BD. Chemotherapy and
      surgery are fairly safe for the treatment of malignancies in BD patients.

PMID- 11529629
TI  - Cerebral atrophy related to corticotherapy in systemic lupus erythematosus (SLE).
AB  - The aim of this study was to evaluate the frequency and intensity of cerebral
      atrophy using CT scanning and the possible relation to corticosteroid therapy or
      disease in systemic lupus erythematosus (SLE) and to analyse the relationships
      between cerebral atrophy and activity disease and neuropsychiatric manifestations
      in lupus patients. We studied 107 consecutive SLE patients (American Rheumatology
      Association 1982 criteria) who were taking steroid drugs at the time and not
      selected for any particular manifestation (group 1). A complete clinical,
      neurological and laboratory evaluation was performed. The American College of
      Rheumatology's classification for neuropsychiatric manifestations and SLE disease
      activity index for activity were employed. Group 2 comprised 39 non-SLE patients
      with oral chronic steroid use (1 mg/k/day for more than 3 consecutive months); 50
      normal individuals were the controls (group 3). There were no demographic
      differences between the groups. Brain CT was performed in all individuals and the
      frequency and the intensity (minimal, moderate and severe) of atrophy analysed,
      through well-defined measures and indices, by two neuroradiologists. Cerebral
      atrophy was significantly more frequent in groups 1 and 2 than in group 3, but
      with no significant difference between groups 1 and 2. The severity of cerebral
      atrophy was significantly higher in SLE patients (p<0.05), independent of steroid
      dose or duration of disease. In both groups no patient presented severe atrophy.
      Lupus patients with and without cerebral atrophy presented neuropsychiatric
      manifestations and activity disease in a similar proportion. The more frequent
      neuropsychiatric manifestation in lupus patients with cerebral atrophy was
      seizures (p<0.05). Chronic glucocorticoid therapy was responsible for cerebral
      atrophy, with a comparable incidence in both lupus and non-lupus patients
      compared to age and gender-matched normal subjects untreated with
      glucocorticoids. The disease activity was not related to cerebral atrophy in
      group 1 and seizures were the neurologic manifestation related to cerebral
      atrophy. The severity of the cerebral atrophy was independent of steroid dose, or
      duration of treatment. Moreover, the disease itself contributes to the severity
      of this process, but not to the development of cerebral atrophy.

PMID- 11529630
TI  - Colonic transit disorders in systemic sclerosis.
AB  - Systemic sclerosis (SS) alters smooth muscle function throughout the
      gastrointestinal tract, the oesophagus being the segment most often involved.
      Involvement of the colon, though less common, may lead to life-threatening
      complications. We studied 23 unselected patients with SS and 20 age-matched
      healthy controls using radionuclide colon transit studies. The geometric centre
      (GC) at 4 and 24 hours was used to summarise overall transit in the colon. In
      patients with SS, colon transit was delayed (GC4: 0.39 +/- 0.36 vs 0.85 +/- 0.45;
      P=0.001) (GC24: 1.68 +/- 0.9 vs 2.58 +/- 1.08; P=0.006). These findings suggest
      that delayed colon transit is common in patients with SS.

PMID- 11529631
TI  - The role of scintigraphy with technetium-99m nanocolloid in patients with
      peripheral joint pain.
AB  - We studied 51 patients with peripheral joint pain to assess the ability of
      technetium-99m-nanocolloid (99mTc NC) scintigraphy to distinguish patients with
      active joint disease from those without, irrespective of their underlying
      aetiology. Patients with peripheral joint pain due to various causes were
      clinically categorised as either having objective signs of active joint disease
      or not. Their clinical diagnoses were not made known to the nuclear physician
      until after scanning. Each patient was given an intravenous injection of 555 MBq
      of 99mTc NC 1 h prior to taking spot views of the peripheral joints. Seventeen
      patients with low backache but without peripheral joint pain were imaged in an
      identical manner to exclude peripheral joint involvement. The latter formed a
      control group. 99mTc NC scintigraphy demonstrated a sensitivity of 89% for
      identifying at least one affected joint per patient, a specificity of 87.5%, a
      negative predictive value (npv) of 87.5%, a positive predictive value (ppv) of
      89%, and overall accuracy of 88%. There were three false negative and three false
      positive cases. The scan was negative in all control subjects. 99mTc NC
      scintigraphy proved to be sensitive in patients with active joint disease and
      demonstrated a good correlation with clinical assessment. The value of the high
      specificity, npv and negative controls together made the test highly
      discriminatory in excluding patients without active peripheral joint disease.

PMID- 11529632
TI  - Survey of factor V leiden and prothrombin gene mutations in systemic lupus
      erythematosus.
AB  - The two most common hereditary risk factors for thrombosis are factor V Leiden
      mutation and a prothrombin gene mutation. There is indeed a thrombotic tendency
      in patients with systemic lupus erythematosis (SLE) and it is not always
      associated with antiphospholipid antibodies. We aimed to determine the
      relationship between both factor V Leiden and prothrombin gene mutations and SLE.
      Using polymerase chain reaction (PCR) the factor V Leiden and prothrombin gene
      mutations were evaluated in 55 patients (20 children and 35 adults) with SLE.
      Although seven patients were found to have factor V Leiden mutation in the
      heterozygous state, two had the heterozygous G-->A (20210) prothrombin gene
      mutation. Although one had these two mutations concurrently, these two patients
      did not have thrombosis. The factor V Leiden mutation frequency (12.7%) was
      higher than that of our general population (7.1%). On the other hand, seven of
      the patients with SLE had a thrombotic event. Although of these seven, four (57%)
      had factor V Leiden mutation, three (43%) had no mutation. Of 48 patients with no
      thrombotic history, only three had the factor V mutation (6.25%). The prevalence
      of the factor V Leiden mutation in SLE patients with and without thrombosis was
      significantly different by Fisher's exact test (p<0.05). The risk of venous
      thrombosis in patients with factor V Leiden increased threefold compared to that
      in those without factor V Leiden mutation (odds ratio 20.1; CI 2.99-133.6).
      Although factor V Leiden mutation seems to play a role in the development of
      venous thrombosis in SLE, the development of thrombosis in SLE is multifactorial.

PMID- 11529633
TI  - Radiologic changes of cervical spine in ankylosing spondylitis.
AB  - Ankylosing spondylitis (AS) is characterised by its effects on the axial
      skeleton. The cervical spine is also vulnerable to the disease process. Our aim
      was to determine the frequency of radiologic changes to the cervical spine and
      their correlation with clinical variables. We also used the Bath Ankylosing
      Spondylitis Radiology Index (BASRI) system, which is one of the reliable scoring
      systems of radiography, to score the global radiologic changes to the cervical
      and lumbar spine and the hip joints in our AS cohort. There were 181 patients
      with anteroposterior and lateral full-flexion views on radiography of the
      cervical spine here included in the study. A radiologist examined the radiologic
      changes to all anatomical compartments of the cervical spine in detail and graded
      them according to the BASRI system. We used the clinical and demographic data of
      our AS cohort to determine their relation to the radiographic changes. Eighty
      eight patients (48.6%) showed radiological changes to the cervical spine; to the
      discovertebral joint 35.9%; the apophyseal joint 26.0%; atlantoaxial articulation
      22.1% (atlantoaxial subluxation 13.8%); the costovertebral joint 18.2%; and to
      the posterior ligamentous attachment 11.6%. Using the BASRI system, 73 patients
      (40.3%) showed radiologic changes to the cervical spine and were graded as score
      1 (1.7%), 2 (22.7%), 3 (6.6%) or 4 (9.4%). Among those graded as normal by the
      BASRI system, 17 showed some changes the cervical spine, such as atlantoaxial
      joint subluxation or narrowing, and severe osteoporosis with no other
      radiographic changes. Current age, disease duration, inflammatory back pain and
      cervical symptoms were associated with the radiographic changes to the cervical
      spine. The BASRI-cervical spine score correlated with the BASRI-lumbar spine and
      hip joint score, sacroiliitis, disease duration, and duration of inflammatory
      back pain and cervical symptoms. Our data suggest that radiographic changes to
      the cervical spine are frequent in AS, and can be predicted in the patients with
      old age, long duration of disease and inflammatory back pain, and cervical
      symptoms. Also, the BASRI scoring system showed similar results as a detailed
      assessment of the cervical spine in our study.

PMID- 11529634
TI  - Recurrent venous thrombosis in Behcet's disease: successful endovascular
      treatment with thrombolysis and stent.
AB  - We report the case of a patient with Behcet's disease (BD) and recurrent venous
      thrombosis in the right subclavian vein, successfully treated with balloon
      dilatation and the insertion of a Wallstent. Subsequent follow up at 6 months
      showed no evidence of reocclusion. Endovascular stents should be considered as a
      possible interventional modality in BD patients with aneurysms or recurrent
      venous or arterial thrombosis.

PMID- 11529635
TI  - Bilateral tibia and fibula fractures in a patient with rheumatoid arthritis.
AB  - A 52-year-old woman with rheumatoid arthritis treated with low-dose steroids
      developed bilateral distal tibia and fibula fractures over a 15-month period. Her
      bone density was within osteopenic levels. Such fractures are an unusual but
      increasingly recognised complication of rheumatoid disease and its treatment,
      although there is often diagnostic delay. Bilateral fractures are particularly
      rare. A high level of clinical suspicion is required for early diagnosis.

PMID- 11529636
TI  - A severely disabling disorder: fibrodysplasia ossificans progressiva.
AB  - Fibrodysplasia ossificans progressiva (FOP) is an extremely rare hereditary
      disorder characterised by progressive heterotopic ossification of the soft
      tissues. The resulting progressive immobilisation of the limbs, jaw and chest
      wall generally leads to severe disability. We present an 18-year-old girl with
      advanced FOP. She had three operative interventions to excise her ectopic bones
      but all resulted in failure. Treatment strategies for this disorder should
      include the avoidance of exacerbating factors.

PMID- 11529637
TI  - Malignant tumor with chest wall pain mimicking Tietze's syndrome.
AB  - Chest pain is commonly caused by musculoskeletal chest wall disorders. Tietze's
      syndrome is a relatively rare cause of chest wall pain characterised by non
      suppurative, painful swelling of the upper costal cartilages. The diagnosis
      should be based on these classic clinical features after excluding other
      potential causes of pain. A patient who was diagnosed with Tietze's syndrome but
      was found to have squamous cell carcinoma of the mediastinum with unknown primary
      site invading the sternum and anterior chest wall is presented for discussion.

PMID- 11529638
TI  - Food allergy and seronegative arthritis: report of two cases.
AB  - The link between food allergy and arthritis is still a matter for debate. Here we
      report two cases of patients suffering from arthritis sustained by food allergy.
      Diagnosis was performed on the basis of a 2-week elimination diet followed by an
      open and double-blind challenge test which was repeated three times. Both
      patients had a previous medical history of food allergy/intolerance. As the
      number of patients with joint complaints sustained by food allergy is very small
      it makes no sense to put all patients on diet. A previous medical history of food
      intolerance is one of the main reasons to start the long and difficult path
      towards a diagnosis of food allergy.

PMID- 11529639
TI  - Kartagener's syndrome and rheumatoid arthritis: an unusual association.
AB  - We report the case of a 66-year-old caucasian woman affected by Kartagener's
      syndrome (KS), a genetically transmitted disorder characterised by situs viscerum
      inversus, bronchiectasis and sinusitis, who also developed rheumatoid arthritis
      (RA). The impaired mucociliary function typical of KS caused recurrent paranasal
      sinus and lung infections, as shown by CT scans of the sinuses and chest. The
      coexistence of KS and RA in our patient was probably accidental. Given the small
      number of patients in whom an association of the two disorders has been
      described, it is impossible to establish whether KS might play a role in the
      pathogenesis of RA.

PMID- 11529640
TI  - Secondary amyloidosis in progressive systemic sclerosis.
AB  - Progressive systemic sclerosis (PSS) is a connective tissue disease that may
      affect many organs, including the kidneys. It is quite rare to see secondary
      amyloidosis due to PSS. We present a patient with a 9-year history of PSS who
      developed nephrotic syndrome, and whose renal biopsy was compatible with
      secondary amyloidosis. He died from massive upper gastrointestinal bleeding
      caused by oesophageal telangiectasia.

PMID- 11529641
TI  - Chronic myeloid leukemia presenting as gout.
AB  - A 53-year-old man presented with gouty arthritis. A physical examination and
      haematological and biochemical tests showed that he had chronic myeloid leukemia.
      He was treated with allopurinol, hydroxyurea and analgesics. The arthritis
      subsided completely within 2 weeks. He continues in haematologic remission (on
      interferon) with no further recurrence of the gout.

PMID- 11529642
TI  - Life-threatening complications of hepatitis B virus-related polyarteritis nodosa
      developing despite interferon-alpha2b therapy: successful treatment with a
      combination of interferon, lamivudine, plasma exchanges and steroids.
AB  - Polyarteritis nodosa (PAN) is a rare vasculitis associated with hepatitis B virus
      (HBV) infection in a significant proportion of cases. When used to treat HBV
      related PAN, immunosuppressive agents may enhance viral replication and relaspes
      are frequent. In recent years the use of antiviral drugs has been proposed. We
      report the case of a patient with HBV-related PAN who, despite 6 weeks of
      interferon-alpha2b (IFN-alpha2b) monotherapy, developed life-threatening
      complications with bowel perforation. He was thereafter successfully treated with
      a combination of IFN-alpha2b, lamivudine, plasma exchanges and short-term
      steroids. In contrast to IFN-alpha2b, lamivudine is effective in rapidly
      suppressing viral replication. This may be valuable in the treatment of HBV
      related PAN by contributing to a faster diminution of circulating immune complex
      levels. This case report highlights the importance of aggressive combined therapy
      in patients with HBV-related PAN.

PMID- 11529643
TI  - Pulmonary haemorrhage in a 6-year-old boy with Henoch-Schonlein purpura.
AB  - Henoch-Schonlein purpura (HSP) is the most common vasculitis in children. It is a
      multisystemic disease but pulmonary haemorrhage is extremely rare. We present the
      case of a 6-year-old boy with Henoch-Schonlein purpura, pulmonary haemorrhage and
      severe renal involvement. The patient responded to a combination of intravenous
      methylprednisolone and cyclophosphamide. A review of the literature revealed that
      young age may be a good prognostic sign and that immunosuppressive drugs and
      supportive management are essential in the treatment. Renal biopsy is helpful in
      the differential diagnosis of HSP-mimicking pulmonary vasculitic syndromes.
      Combining cyclophosphamide with glucocorticoids may improve the outcome in severe
      HSP cases with pulmonary haemorrhage.

PMID- 11529644
TI  - Rheumatoid arthritis induced by alpha-interferon therapy.
AB  - Interferon (IFN) therapy has been used for the treatment of common diseases such
      as hepatitis C, myeloproliferative disorders, autoimmune diseases and various
      types of cancer. Given the biological properties of interferon, it is not
      surprising that there are a larger number of side effects due to its use.
      Although rheumatoid arthritis (RA) is one of the most common autoimmune diseases
      found in clinical practice, it does not seem to be frequently related to IFN
      therapy. We report a 40-year-old female patient who, after high doses of IFN
      alpha therapy for malignant melanoma, developed symmetrical polyarthritis, with
      pain and oedema in small and large joints, associated with prolonged morning
      stiffness. She had positive rheumatoid factor and DR4 HLA phenotype. She was
      treated with deflazacort (6 mg/day), chloroquine and NSAIDs, with a partial
      response. In conclusion, although the development of RA after IFN therapy is a
      rare event, IFN may work as a 'trigger' for such complication, leading to
      deregulation in the immune cascade in a person genetically predisposed.

PMID- 11529645
TI  - A decreased serum leptin level in patients with systemic sclerosis.
AB  - Serum leptin levels were determined in 31 women with systemic sclerosis and 24
      age-matched healthy controls. Both groups were divided into premenopausal and
      postmenopausal subgroups. A decreased serum leptin was found in the patients with
      systemic sclerosis. The premenopausal patients and controls had higher serum
      leptin than those in the postmenopausal subgroups. Serum leptin correlated with
      body mass index in the patients with systemic sclerosis.

PMID- 11529646
TI  - Reactive arthritis in Brazil.

PMID- 11529647
TI  - Blue-coloured skin over involved joints in psoriatic arthritis.

PMID- 11529648
TI  - 5-Aminosalicylates in inflammatory bowel disease: choosing the right dose.

PMID- 11529649
TI  - Helicobacter pylori and liver: an actor with three roles?

PMID- 11529650
TI  - Tissue transglutaminase antibodies: is sensitivity more important than
      specificity?

PMID- 11529651
TI  - Prevalence of peptic lesions in asymptomatic, healthy volunteers.
AB  - AIM: To investigate the presence of lesions of the upper gastrointestinal tract
      of asymptomatic, healthy volunteers undergoing clinical pharmacology studies.
      MATERIAL AND METHODS: A series of 53 volunteers (45 male, 23 Helicobacter pylori
      negative and 30 Helicobacter pylori positive) underwent upper gastrointestinal
      endoscopy. Helicobacter pylori status was assessed using two methods (rapid
      urease test and histology) from antral and corpus biopsies. RESULTS: Peptic
      lesions were found in 24 (45%) subjects: erosive oesophagitis, gastric/duodenal
      ulcers and gastric/duodenal erosions were found in 23%, 9% and 36% of these
      volunteers, respectively. Helicobacter pylori-positive subjects had significantly
      (p<0.05) more gastroduodenal lesions than Helicobacter pylori negative
      individuals (12/30 vs 3/23). The presence of peptic ulcers and erosive
      oesophagitis was similar in Helicobacter pylori-positive and -negative
      individuals. CONCLUSIONS: The possibility that peptic lesions might exist in
      otherwise asymptomatic, healthy individuals cannot be ruled out. Helicobacter py
      lori-positive individuals have a significantly higher incidence of gastric and
      duodenal lesions than Helicobacter pylori negative subjects.

PMID- 11529652
TI  - Effect of cisapride on gastric sensitivity to distension, gastric compliance and
      duodeno-gastric reflexes in healthy humans.
AB  - BACKGROUND AND AIMS: Visceral hypersensitivity and impaired gastric relaxation
      after the ingestion of a meal are frequent features in patients with functional
      dyspepsia. Cisapride improves dyspeptic symptoms. The study aims to evaluate
      whether cisapride influences gastric sensitivity to distension as well as gastric
      compliance and duodenogastric reflexes. PATIENTS AND METHODS: Eight healthy males
      were studied on two different days, each after 7 days' treatment either with
      placebo or cisapride 10 mg qid in randomized order. A spherical bag connected to
      a barostat was placed in the gastric fundus and an 8-lumen manometric catheter
      was positioned with 4 side holes in antrum and 4 in duodenum. During a phase II
      of the migrating motor complex, the intragastric bag was inflated at a constant
      pressure 1 mm Hg above the intra-abdominal pressure and the gastric volume was
      measured during intraduodenal infusion of lipids and citric acid at different
      rates. Once the stomach returned to the basal volume, the bag was distended
      according to two different protocols until subjects reported discomfort.
      Antroduodenal motility was measured throughout the study. RESULTS: Intraduodenal
      infusion of lipids and citric acid caused relaxation of gastric fundus.
      Relaxation was similar for lipids and acid (203 +/- 30 vs 199 +/- 43 ml), and was
      not influenced by cisapride and infusion rate. Cisapride did not influence
      gastric sensitivity to distension (10 +/- 1.5 vs 9.7 +/- 1.3 mm Hg) and gastric
      compliance (52.7 +/- 1.2 vs 49.8 +/- 1.8 ml/mm Hg). The antral motor index
      significantly decreased following infusion of acid and lipids with placebo but
      not with cisapride. CONCLUSIONS: Cisapride inhibits the physiological
      duodenoantral reflexes but does not influence either the mechanical properties of
      the gastric fundus nor the gastric sensitivity to distension.

PMID- 11529653
TI  - Helicobacter pylori is not a risk factor for hepatic encephalopathy.
AB  - BACKGROUND: Helicobacter pylori infection has been described as a risk factor for
      hepatic encephalopathy in patients with chronic liver disease although the topic
      remains controversial. AIMS: To determine whether Helicobacter pylori infection
      is an independent predictive factor for encephalopathy in patients with liver
      cirrhosis. METHODS: Clinical, epidemiological, analytical and nutritional
      parameters of 205 patients were collected. Helicobacter pylori infection was
      determined by serology. Encephalopathy (grade II or higher) was clinically
      assessed during follow-up. The relationship between each parameter and
      encephalopathy was analysed by Kaplan-Meier curves and the Log rank test. The
      most significant parameters underwent multivariate analysis by Cox regression.
      RESULTS: Twenty-five variables were related to encephalopathy in the bivariate
      analysis. Multivariate analysis selected five independent factors: previous bouts
      of encephalopathy (Odds ratio 3.79; 95% confidence interval 1.94-7.38), albumin
      (Odds ratio 0.86; 95% confidence interval 0.80-0.92), tricipital skin fold (Odds
      ratio 0.79; 95% confidence interval 0.66-0.95) chronic pulmonary disease (Odds
      ratio 2.78, 95% confidence interval; 1.31-5.92), and on-going alcoholism (Odds
      ratio 2.62; 95% confidence interval 1.16-5. BB). CONCLUSIONS: Helicobacter pylori
      is not an independent risk factor for hepatic encephalopathy.

PMID- 11529654
TI  - Anti tissue transglutaminase antibodies as predictors of silent coeliac disease
      in patients with hypertransaminasaemia of unknown origin.
AB  - BACKGROUND: Unexplained hypertransaminasaemia can be regarded as an
      extraintestinal presentation of coeliac disease. AIM: To evaluate the reliability
      of immunoglobulin A anti tissue transglutaminase antibodies for identifying
      coeliac disease in those patients with raised transaminases of unknown origin.
      PATIENTS: Of 1,120 consecutive patients referred to the outpatient clinic for
      liver disease due to raised transaminases from September 1995 to December 1999,
      110 were classified as having cryptogenic hypertransaminasaemia after the
      exclusion of every known cause of liver disease. METHODS: These 110 patients were
      tested for immunoglobulin A anti tissue transglutaminase and antiendomysial
      antibodies by enzyme-linked immunosorbent assay and indirect immunofluorescence,
      respectively. RESULTS: Ten patients resulted positive for both antibodies; in all
      of them duodenal biopsy showed a subtotal villous atrophy consistent with coeliac
      disease. They did not complain of any gastrointestinal symptom. Liver biopsy,
      performed in five, showed a histological picture of non-specific reactive
      hepatitis. CONCLUSIONS: Due to the high proportion (9.15%) of patients with
      cryptogenic hypertransaminasaemia affected by symptomless coeliac disease,
      serological screening for gluten-sensitive enteropathy must be included in the
      work-up of these patients. In this respect, anti tissue transglutaminase
      antibodies represent a valid alternative to antiendomysial antibodies with the
      advantage of being feasible everywhere thanks to the worldwide availability of
      enzyme-linked immunosorbent assay.

PMID- 11529656
TI  - Report of a life-threatening arrhythmia after hospital discharge in a liver
      transplant recipient with previously unknown congenital long QT syndrome.
AB  - The long QT syndrome affects heart rhythm by prolonging ventricular
      repolarisation; it is potentially life-threatening since it can evolve into
      torsades de pointes (a polymorphic ventricular tachycardia) and/or ventricular
      fibrillation. The case is presented of a 55-year-old liver transplant recipient
      with a genetically determined long QT syndrome not detected by the standard
      preoperative cardiological evaluation. It was mild in the immediate post
      operative period but developed into torsades de pointes after discharge, probably
      as a result of therapy. This case was particularly challenging because the first
      arrhythmic episodes were short and electocardiographically silent, and thus the
      related faints were thought to have a neurological basis. When the true cause
      emerged during a monitored episode of torsades de pointes, electric
      defibrillation was used to restore sinus rhythm and isoproterenol administered to
      increase heart rate and thus shorten the prolonged QT interval Long-term control
      was obtained by means of an implantable intracardiac defibrillator. In orthotopic
      liver transplant recipients with long QT syndrome, particular attention should be
      given to post-operative therapy as some routinely used drugs can trigger life
      threatening ventricular arrhythmias.

PMID- 11529655
TI  - Serological markers for coeliac disease: is it time to change?
AB  - BACKGROUND: Anti-gliadin and anti-endomysium antibodies are useful markers in the
      screening and follow-up of coeliac disease. The recent finding that tissue
      transglutaminase is the main auto-antigen of anti-endomysium has led to the
      discovery of anti-tissue transglutaminase antibodies. AIM: To compare, in a
      prospective study, the diagnostic accuracy of anti-tissue transglutaminase, anti
      gliadin and anti-endomysium antibodies in a large series of adult patients.
      METHODS: The study involved 80 consecutive subjects undergoing upper
      gastrointestinal tract endoscopy for suspected coeliac disease (subsequently
      confirmed in 40 cases), 195 coeliac patients on a gluten-free diet, and 70
      patients with different gastrointestinal disor ders and normal duodenal
      histology. Anti-gliadin, anti-endomysium and anti-tissue transglutaminase
      antibodies levels were measured using commercial kits. RESULTS: The diagnostic
      sensitivity and specificity of anti-gliadin, anti-endomysium and anti-tissue
      transglutaminase antibodies were, respectively, 95% and 89.1%, 100% and 97.3%,
      and 100% and 98.2%: the agreement between the markers was substantial or almost
      perfect. In terms of follow-up, the positivity of the markers varied according to
      the strict adherence to, and duration of the gluten-free diet; the agreement
      between antiendomysium and anti-tissue transglutaminase antibodies was almost
      perfect. CONCLUSIONS: Anti-endomysium and anti-tissue transglutaminase antibodies
      are both highly efficient for routine laboratory screening: the choice of one or
      the other will depend on the available facilities. However, neither can replace
      intestinal biopsy for general population screening because, in this case, their
      respective positive predictive values are only 15.7% and 21.8%. During follow-up,
      anti-gliadin retain their value as an early predictor of gluten ingestion.

PMID- 11529657
TI  - Colonoscopic removal of a polypoid arteriovenous malformation.
AB  - A 53-year-old male presenting with a 3-month history of intermittent mild rectal
      bleeding was found, on double contrast barium enema, to have a large polyp on a
      long stalk in the sigmoid colon. Large bowel endoscopy confirmed the presence of
      a 2 cm pedunculated polyp which was removed using a diathermic snare, with slight
      bleeding following the procedure that did not require endoscopic haemostasis.
      Only after histologic examination was the polyp shown to be a colonic
      arteriovenous malformation. Endoscopically, arteriovenous malformations generally
      appear as flat or elevated bright red lesions. A pedunculated polypoid appearance
      is extremely uncommon. In this case, no gastrointestinal bleeding or polypoid
      recurrence was observed during the 12 months of clinical and endoscopic follow
      up.

PMID- 11529658
TI  - Treatment of liver metastases from colorectal cancer: what is the best approach
      today?
AB  - Liver is the common site for metastases from colorectal cancer. The 5-year
      overall survival rate of patients following radical operations is 25%. Surgery
      can be carried out in only 10-15% of the patients, yet it remains the potential
      curative treatment for resectable lesions. For the unresectable cancers, only
      chemotherapy is recommended. New drugs such as Irinotecan prolongs the overall
      survival of patients affected by advanced disease. In patients with unresectable
      metastases at diagnosis, pre-surgical treatment with Oxaliplatin leads to
      reduction of the lesions, allowing resection in 16% of cases. Chemotherapy may be
      delivered directly into the liver via the hepatic artery. No, clinical trials, to
      date, have shown convincing survival results in patients treated with this
      procedure. Combined hepatic artery and systemic treatment may provide a new
      strategy as adjuvant therapy for patients undergoing resections.

PMID- 11529659
TI  - Triplex-forming molecules: from concepts to applications.
AB  - The ability to specifically manipulate gene expression has wide-ranging
      applications in experimental biology and in gene-based therapeutics. The design
      of molecules that recognise specific sequences on the DNA double helix provides
      us with interesting tools to interfere with DNA information processing at an
      early stage of gene expression. Triplex-forming molecules specifically recognise
      oligopyrimidine-oligopurine sequences by hydrogen bonding interactions.
      Applications of such triplex-forming molecules (TFMs) are the subject of the
      present review. In cell cultures, TFMs have been successfully used to down- or up
      regulate transcription in a gene-specific manner and to induce genomic DNA
      modifications at a selected site. The first evidence of a triplex-based activity
      in animals has been provided recently. In addition, TFMs are also powerful tools
      for gene-specific chemistry, in particular for gene transfer applications.

PMID- 11529660
TI  - Transduction of CD34+ cells with lentiviral vectors enables the production of
      large quantities of transgene-expressing immature and mature dendritic cells.
AB  - BACKGROUND: Genetically engineered dendritic cells (DC) presenting specific
      antigens to T cells may be of great interest for immunotherapy. For this reason,
      the production of transgene-expressing DC derived from CD34 + cells transduced
      either shortly after ex vivo purification or during their differentiation into DC
      were evaluated. METHODS: CD34+ cells were transduced with lentivectors encoding
      for GFP before or after 21 days of culture with FLT3-ligand, thrombopoietin and
      stem cell factor and induction into DC with GM-CSF+IL-4 (G4) or G4+TNF (GT4). GFP
      and DC-specific marker expression was assessed by flow cytometry, and
      allostimulatory capacity was evaluated on GFP+ and GFP- sorted cells. RESULTS:
      Immature (G4-induced) DC obtained from amplified CD34 + cells were transducible
      by lentiviral vectors while mature (GT4-induced) DC were rather refractory.
      Moreover, since differentiated DC did not proliferate, large quantities of
      vectors were required to generate transgene-expressing cells with this protocol.
      In contrast, greater numbers of both immature and mature GFP- expressing DC were
      obtained with CD34+ cells exposed to lentivector shortly after purification. By
      the time of DC induction, GFP+ cells had increased by approximately 170-fold.
      After DC induction with G4, 32% of CD1a+, HLA-DR+, or CD40+ cells expressed GFP.
      CD1a+E-cadherin+ GFP+ Langerhans-like DC were also obtained. Incubation with TNF
      induced mature CD83+GFP+ DC that displayed a higher allostimulatory capacity than
      cells induced with G4 alone. CONCLUSION: The transduction of a small number of
      CD34+ cells with minimal doses of lentivector may allow for the production of a
      large number of DC expressing selected antigens useful for immunotherapy.

PMID- 11529661
TI  - EC-SOD gene therapy reduces paracetamol-induced liver damage in mice.
AB  - BACKGROUND: Paracetamol overdose causes acute liver damage which leads to severe
      centrilobular hepatic necrosis. The hepatotoxic effect is caused by reactive
      metabolites and oxidative stress. Since extracellular superoxide dismutase (EC
      SOD) protects tissues against the harmful effects of superoxide anion, the
      hypothesis that systemic adenovirus-mediated EC-SOD gene transfer could reduce
      liver damage was tested. METHODS: Mice were given paracetamol (600 mg/kg)
      enterally 2 days after adenovirus-mediated gene transfer of EC-SOD (2 x 10(9)
      pfu). Five days after gene transfer, plasma and tissue samples were collected for
      clinical chemistry analyses and tissue pathology evaluation. RESULTS: EC-SOD was
      expressed in a dose-dependent manner with the highest enzyme activity occurring 3
      days after the gene transfer. Clinical chemistry and tissue pathology analyses
      showed that adenoviral EC-SOD gene transfer significantly attenuated release of
      liver enzymes and inhibited necrosis and apoptosis caused by paracetamol
      overdose. CONCLUSION: The results indicate the involvement of superoxide anion in
      paracetamol-mediated liver damage and suggest a possible protective role for EC
      SOD gene transfer in paracetamol-induced liver damage.

PMID- 11529662
TI  - Transduction of human MCP-3 by a parvoviral vector induces leukocyte infiltration
      and reduces growth of human cervical carcinoma cell xenografts.
AB  - BACKGROUND: The oncosuppressive properties of some autonomous parvoviruses such
      as H-1 virus, together with their low pathogenicity, make them attractive vectors
      for tumor-directed gene therapy. Indeed, it was recently shown that these viruses
      became endowed with an enhanced oncosuppressive activity after they had been
      engineered to deliver a recognized therapeutic transgene. This prompted us to use
      a parvoviral vector to analyse the antineoplastic capacity of MCP-3 (monocyte
      chemotactic protein-3), a CC chemokine which has a broad spectrum of target
      cells, and can thus be considered to be a promising candidate for cancer
      treatment. METHODS: We explored the use of a parvovirus H-1-based vector encoding
      human MCP-3 for its antitumor potential on human cervical carcinoma cells. HeLa
      cells were infected in vitro with the recombinant virus hH1/MCP-3 at a low
      multiplicity [1 replication unit (RU)/cell] and we investigated the effect of
      parvovirus-mediated MCP-3 transduction on tumor formation and growth upon
      implantation of HeLa cells in nude mice. RESULTS: Infection of HeLa cells with
      hH1/MCP-3 led to secretion of high levels of MCP-3 and to significant retardation
      of tumor growth in recipient mice, as compared with HeLa cells that were either
      buffer-treated or infected with a MCP-3-free vector. Tumors from hH1/MCP-3
      infected HeLa cells were heavily infiltrated with activated macrophages and
      showed increased numbers of dendritic cells. In addition, activated natural
      killer (NK) cells were also recruited into MCP-3-transduced tumors. CONCLUSION:
      These observations indicate that parvovirus H-1-transduced MCP-3 is able to exert
      a significant antitumor activity which is mediated, at least in part, through
      macrophages and NK cells, under conditions in which activated T cells are
      lacking.

PMID- 11529663
TI  - Improved in vitro gene transfer mediated by fluorinated lipoplexes in the
      presence of a bile salt surfactant.
AB  - BACKGROUND: Progress in the field of gene transfer with non-viral vectors
      requires systems that allow efficient gene expression in the presence of
      biological fluids such as pulmonary surfactants, for gene transfer to the
      respiratory epithelium for cystic fibrosis gene therapy, or bile salts (which
      contain powerful anionic detergents), for gene transfer to the biliary epithelium
      for gene therapy of the hepatobiliary disease associated with cystic fibrosis
      (CF). We have performed a comparative analysis of the disintegration and DNA
      accessibility of fluorinated and conventional lipoplexes, and their in vitro
      transfection potential in the presence of a powerful biliary surfactant. METHODS:
      The disintegration and DNA accessibility of conventional and fluorinated cationic
      lipoplexes and their in vitro transfection efficiency of human lung carcinoma
      epithelial A549 cells were studied in the presence of various concentrations of
      sodium taurocholate (STC), an anionic bile salt detergent. The conventional and
      fluorinated lipoplexes were formulated from Transfectam" (or DOGS) and from
      fluorinated lipospermines, analogs of DOGS, respectively, and a luciferase
      reporter plasmid. The fluorinated lipids used in the present study were selected
      for their different degrees of fluorination in order to investigate the impact on
      stability and transfection. The effects of the detergent on lipoplex integrity
      were examined by evaluating the ability of the lipospermines to prevent, in the
      presence of the surfactant, ethidium bromide (BET) intercalation into the plasmid
      (fluorescence monitoring). RESULTS: Fluorinated cationic lipoplexes exhibited
      greater stability than DOGS lipoplexes with respect to STC lytic activity.
      Indeed, while the DOGS lipoplexes were fully disintegrated at a [STC]/[lipid]
      molar ratio of 1,320, all the DNA intercalation sites of the most fluorinated
      lipoplexes investigated became accessible to BET for a two-fold higher
      [STC]/[lipid] molar ratio. A higher transfection potential in the presence of the
      detergent was also shown for the fluorinated lipoplexes as compared with the DOGS
      preparation. At a 10 mM concentration of STC and at a [STC]/[lipid] molar ratio
      of 264, lipofection when mediated by DOGS was fully inhibited while the detergent
      had no inhibitory effects on the lipofection mediated by the fluorinated DF4C11
      GS [spermine-5-carboxyglycine N,N-di-11-(F-butyl)-undecylamide] or DF6E11-GS
      [spermine-5-carboxyglycine N,N-di-[11-(F-hexyl)-undec-10-enyl]amide]
      lipospermines. A higher detergent concentration (up to 17.5 mM) and a higher
      [STC]/[lipid] ratio (up to 462) were necessary to inhibit lipofection by the
      fluorinated formulations. Overall, the lipoplex stability and transfection
      potential in the presence of the detergent was found to improve with increasing
      degrees of fluorination of the lipospermines. CONCLUSIONS: The present work shows
      improved stability of, and higher lipofection levels with, fluorinated lipoplexes
      in the presence of surfactants. The results confirm the very promising potential
      of fluorinated lipoplexes as gene transfer vectors. These compounds constitute a
      very attractive alternative to their more conventional homologs. The correlation
      found between the degree of fluorination of the lipoplexes, their stability and
      their lipofection levels suggests that enhanced lipophobic and hydrophobic
      properties protect them against disintegration and, consequently, prevents DNA
      from being degraded and from interacting with lipophilic and hydrophilic
      biocompounds responsible for lipofection inhibition.

PMID- 11529664
TI  - EBV replicon vector system enhances transgene expression in vivo: applications to
      cancer gene therapy.
AB  - BACKGROUND: A major limitation of current cancer gene therapies is low and
      transient expression of the therapeutic gene. For long-term expression of
      transgenes in vivo, an Epstein-Barr virus (EBV) replicon vector has been
      developed. The present study examines the effect of the EBV replicon vector
      system and its application to a suicide gene therapy for melanoma in mice.
      METHODS: An EBV replicon vector system, pEBc, consisting of EBV nuclear antigen-1
      (EBNA-1) and the origin of latent viral DNA replication, oriP, was used to
      express either the luciferase gene or the herpes simplex virus (HSV) thymidine
      kinase (TK) gene. The expression vector was introduced in vivo into melanoma
      tumor masses in mice by means of HVJ-cationic liposomes. The time-course of gene
      expression and the anticancer effect of the EBV replicon vector were investigated
      in comparison with pcLuc, which lacks the EBV components. RESULTS: Luciferase
      expression was sustained in both cultured cells and melanoma masses by pEBc but
      not by pcLuc. The luciferase expression level in melanoma masses was higher by
      pEBcLuc than by pcLuc, although Southern blot analysis showed the number of
      copies of pEBcLuc retained in the melanoma masses to be fewer than that of pcLuc.
      The effectiveness of EBV replicon vector on suicide gene therapy of melanoma in
      mice was also demonstrated. CONCLUSION: The EBV replicon vector appears useful
      for cancer gene therapy. Analysis of the transgene in tumors suggests that the
      EBV replicon system may be responsible for efficient transcription but not
      retention of the transgene.

PMID- 11529665
TI  - Combined transductional and transcriptional targeting of melanoma cells by
      artificial virus-like particles.
AB  - BACKGROUND: Artificial virus-like particles (AVPs) represent a novel type of
      liposomal vector resembling retroviral envelopes. AVPs are serum-resistant and
      non-toxic and can be endowed with a peptide ligand as a targeting device. The
      vitronectin receptor, alphavbeta3-integrin, is commonly upregulated on malignant
      melanoma cells. In the present study we investigated whether AVPs carrying cyclic
      peptides with an RGD integrin binding motif (RGD-AVPs) are suitable for the
      specific and efficient transduction of human melanoma cells. METHODS: Plasmid DNA
      was complexed with low molecular weight non-linear polyethyleneimine and packaged
      into anionic liposomes. Transduction efficiencies were determined after transient
      transfection of different cell lines in serum-free medium using green fluorescent
      protein or luciferase reporter genes. RESULTS: We demonstrated that RGD-AVPs
      transduced human melanoma cells with high efficiencies of > 60%. Efficient
      transduction was clearly dependent on the presence of the cyclic RGD ligand and
      was selective for melanoma cells. The specificity of the vector system could be
      further enhanced by using the melanocyte-specific tyrosinase promoter to drive
      transgene expression. CONCLUSION: Our findings suggest that the AVP technology is
      a useful approach for generating highly efficient and specific non-viral vectors
      for melanoma targeting, in particular in a setting of combined transductional and
      transcriptional targeting.

PMID- 11529666
TI  - Different behavior of branched and linear polyethylenimine for gene delivery in
      vitro and in vivo.
AB  - BACKGROUND: Efficient gene transfer is a major challenge for non-viral gene
      therapy. Understanding how non-viral vectors initiate gene expression could lead
      to the development of new future vectors with enhanced efficacy. METHODS: Linear
      or branched polyethylenimine (PEI)/DNA complexes were generated in varying salt
      conditions and their transfection efficiencies were compared in vitro and in vivo
      using reporter genes, luciferase and green fluorescent protein, and rhodamine
      labeled DNA (pGeneGrip). RESULTS: The transfection efficiency of linear PEI22/DNA
      in vitro was generally greater than that of branched PEI/DNA when complexes were
      generated in salt containing buffer. However, PEI complexes generated under salt
      free conditions generally had low transfection activity in vitro. In contrast,
      PEI22/DNA salt-free complexes were highly active in vivo. Branched PEI/DNA and
      salt containing PEI22/DNA complexes were generally 10-100-fold less active than
      the salt-free PEI22/DNA complexes. Salt-free PEI22/DNA complexes were small, but
      subsequently grew into aggregates when salt was added. In contrast, PEI25/DNA
      complexes remained small even after salt was added under the same conditions.
      Furthermore, PEI22/pGeneGrips complexes formed large aggregates associated with
      the cell membrane, cytoplasm and nucleus, while branched PEI complexes remained
      as small distinct particles associated with the cell membrane or in the
      cytoplasm. CONCLUSIONS: Branched and linear PEI/DNA complexes differ in their
      ability to transfect cells. The greater efficiency of linear PEI might be due to
      an inherent kinetic instability under salt conditions. Understanding how to
      employ this kinetic instability of linear PEI could help in designing future
      vectors with greater flexibility and transfection efficiency in vivo.

PMID- 11529667
TI  - In vivo use of oligonucleotides to inhibit choroidal neovascularisation in the
      eye.
AB  - BACKGROUND: We have previously demonstrated the in vivo uptake of
      oligonucleotides in the rat eye and have continued with experiments to look at
      the effectiveness of targeted oligonucleotide sequences. Vascular endothelial
      growth factor (VEGF) is correlated with new blood vessel formation and has been
      implicated in numerous eye diseases characterised by abnormal blood vessel
      proliferation. An oligonucleotide targeted to the VEGF sequence was examined for
      its effect on VEGF production in vitro and the development of choroidal
      neovascularisation in vivo in the eye. METHODS: A series of sequences were
      assessed in an in vitro screening system using retinal pigment epithelial (RPE)
      cells to demonstrate a reduction in VEGF. A targeted sequence was further
      investigated using an animal model of choroidal neovascularisation where a
      krypton laser was used to produce a wound healing response in the choroid and
      retina. The oligonucleotide was injected into the vitreous and the development of
      choroidal neovascularisation assessed using fluorescein angiography. RESULTS: The
      targeted sequence was shown in vitro to downregulate the VEGF produced by RPE
      cells grown under hypoxic conditions and when injected into laser treated eyes
      was shown to be preferentially taken up in the laser lesion. Fluorescein
      angiography demonstrated that the test oligonucleotide was successful in reducing
      laser-mediated choroidal neovascularisation. CONCLUSIONS: A sequence
      corresponding to the 5'UTR of the VEGF gene has provided encouraging results for
      the treatment of neovascularisation.

PMID- 11529668
TI  - Systemic production of IL-12 by naked DNA mediated gene transfer: toxicity and
      attenuation of transgene expression in vivo.
AB  - BACKGROUND: IL-12 is a potent antitumor cytokine for cancer gene therapy.
      Previously, we demonstrated that single systemic administration of naked DNA
      (encoding IL-12) could serve as a good model for in vivo evaluation of the
      antitumor effect of a candidate gene (unpublished data). In the present study, we
      propose that this gene delivery method could be a very useful model for in vivo
      evaluation of the toxicity of a given therapeutic gene (using IL-12 as an
      example). By comparing the toxicities and the effects of initial IL-12
      administration on subsequent transgene expression, both IL-12 gene delivery and
      recombinant murine IL-12 protein (rmIL-12) administration showed similar toxicity
      profiles. METHODS: Naked DNA encoding murine IL-12 (mIL-12) was delivered into
      mice by systemic administration. Toxicity profiles of mice treated with DNA or
      rmIL-12 were compared. RESULTS: Systemic administration of naked DNA encoding mIL
      12 resulted in very similar toxicity as rmIL-12 with respect to liver enzyme,
      hematological and immunological profiles. Repeated injection of mIL-12 gene did
      not recover a high level of mIL-12 production as the first injection. Moreover,
      initial mIL-12 administration resulted in inhibition of subsequent reporter gene
      expression with both viral and non-viral promoters (CMV, human alpha-antitrypsin
      or chicken beta-actin promoter). This transgene inhibition effect was entirely
      mediated by IFN-gamma as the transgene expression was fully recovered in IFN
      gamma knockout mice. CONCLUSIONS: Systemic IL-12 therapy, with either a protein
      or gene therapy approach, resulted in comparable liver and systemic toxicities.
      Refractoriness of mIL-12 production by subsequent administration of mIL-12 gene
      was observed. The transgene attenuation effect of IL-12 pre-dosing (either by IL
      12 or rmIL-12), mediated by IFN-gamma, provided important insights for the design
      of IL-12 combination gene therapy and the improvement of gene vectors for IL-12
      therapy. The present results show that simple injection of naked DNA could serve
      as a good model for in vivo evaluation of the toxicity of a candidate therapeutic
      gene.

PMID- 11529669
TI  - Tamarin alpha-interferon is active in mouse liver upon intramuscular gene
      delivery.
AB  - BACKGROUND: The hepatitis C virus (HCV) is responsible for a severe and
      widespread form of hepatitis for which a durable and effective therapy has not
      yet been established. The only approved therapy against hepatitis C, alpha
      interferon protein intramuscular administration, presents numerous drawbacks that
      might be overcome by adopting a gene therapy approach. HCV exclusively infects
      humans and chimpanzees, hence an acceptable animal model for hepatitis C
      pharmacological studies is not available. Recently, tamarins infected by GB virus
      B (GBV-B) have been proposed as a surrogate animal model for HCV infection. The
      aim of the present study was the production of tamarin interferon (tIFN) through
      delivery of tIFN-coding DNA to evaluate the feasibility of a gene therapy
      approach based on IFN electro-gene transfer (EGT) in future studies with
      primates. METHODS: Production and biological activity of cloned tamarin
      interferon was monitored in cultured cells upon transfection and in mice upon
      muscle EGT of the corresponding plasmid DNA, respectively. RESULTS: A tamarin
      gene encoding a protein homologous to human interferon-alpha2 (hIFN-alpha2) has
      been cloned. The tamarin IFN-alpha (tIFN-alpha) protein shows antiviral activity
      in a cell-based assay. Upon EGT of the corresponding gene in mouse muscles, tIFN
      alpha is detectable at high levels in serum for at least 4 months. Most
      important, activity of tIFN, measured as enhancement of mRNA levels of genes
      induced by type I IFNs, is also detectable in the liver of EGT-treated mice.
      CONCLUSION: The present study demonstrates that the delivery of tIFN-alpha DNA
      via intramuscular injection yields a functional protein able to produce
      biological effects inside a remote target organ, the liver. This finding, besides
      the specific purpose of the present study, is of general relevance with a view to
      establishing therapeutic protocols based on EGT.

PMID- 11529670
TI  - Source monitoring and false memories in children: relation to certainty and
      executive functioning.
AB  - We presented children aged 6, 8, and 10 years with a video and then an audio tape
      about a dog named Mick. Some information was repeated in the two sources and some
      was unique to one source. We examined: (a) children's hit rate for remembering
      whether events occurred and their tendency to make false alarms, (b) their memory
      for the context in which events occurred (source monitoring), (c) their certainty
      about hits, false alarms, and source, and (d) whether working memory and
      inhibition were related to hits, false alarms, and source monitoring. The
      certainty ratings revealed deficits in children's understanding of when they had
      erred on source questions and of when they had made false alarms. In addition,
      inhibitory ability accounted for unique variance in the ability to avoid false
      alarms and in some kinds of source monitoring but not hits. In contrast, working
      memory tended to correlate with all forms of memory including hits.

PMID- 11529671
TI  - Executive control within strategic deception: a window on early cognitive
      development?
AB  - Recently it has been claimed that the difficulty young children have with tests
      of strategic deception may be due to limitations in executive control rather than
      lack of insight into mental concepts. In the studies reported here we asked how
      reducing the executive demands of one measure of strategic deception, the windows
      task (J. Russell, N. Mauthner, S. Sharpe, & T. Tidswell, 1991), would affect
      performance. Study 1 demonstrated that both providing an artificial response
      medium and having children play in partnership enabled 3-year-olds to adopt a
      successful strategy. Study 2 examined whether social or executive factors
      accounted for the good performance of children when they played in partnership.
      Study 3 ruled out the possibility that the effectiveness of the artificial media
      was a result of reducing social intimidation-the manipulations were effective
      even in the presence the opponent. These results argue for executive factors
      playing a substantial role in the development of strategic deception.

PMID- 11529672
TI  - Temporal bisection in children.
AB  - Children aged 3, 5, and 8 years received training on a temporal bisection task,
      with standard short and long durations being presented as visual stimuli lasting
      1 and 4 s or 2 and 8 s. Nonstandard comparison stimuli were spaced linearly
      between the standards. Psychophysical functions showed increasing proportions of
      "long" responses (responses appropriate to the long standard) with increasing
      stimulus duration, but were flatter in the younger children than in the 8-year
      olds. Bisection points (the stimulus duration giving rise to 50% "long"
      responses) were close to the arithmetic mean of the short and long standards in
      most conditions. Statistical analyses and results from different theoretical
      models of the data all suggested that temporal sensitivity was higher in the 8
      year-olds than in the younger groups, even when the possibility of random
      responding was controlled for.

PMID- 11529673
TI  - The relationship between paired associate learning and phonological skills in
      normally developing readers.
AB  - Seventy-five 6- to 11-year-old children were administered tests of phonological
      awareness, verbal short term memory (STM), and visual-verbal paired associate
      learning (PA learning) to investigate their relationship with word recognition
      and decoding skills. Phonological awareness was a stronger concurrent predictor
      of word recognition than verbal STM, and phonological awareness but not verbal
      STM was a predictor of learning in the PA learning task. Importantly, measures of
      phonological awareness and PA learning both accounted for independent variance in
      word reading, even when decoding skill was controlled. The results suggest that
      PA learning and phonological awareness tasks tap two separate mechanisms involved
      in learning to read. The results are discussed in relation to current theories of
      reading development.

PMID- 11529674
TI  - Reexposure breeds recall: effects of experience on 9-month-olds' ordered recall.
AB  - On the basis of three experiences, 9-month-olds recall specific events after one
      month. We tested whether multiple experiences are necessary, or merely
      facilitative, of 9-month-olds' long-term recall. In two experiments, using
      deferred imitation, infants were exposed to multi-step sequences either one time,
      two times, or three times prior to a one-month delay. In Experiment 1, regardless
      of the number of experiences, infants did not demonstrate recall. In Experiment
      2, infants were tested on and reexposed to the events after one week; recall was
      tested again one month later. Performance after 1 week in Experiment 2 was
      greater than performance after one month in Experiment 1. Moreover, presumably as
      a function of reexposure after one week, infants recalled the individual actions
      of the events one month later. Infants in the three-experience condition also
      evidenced ordered recall after one month. Implications for the developmental
      status of the neural substrate supporting long-term recall are discussed.

PMID- 11529675
TI  - Crosstalk between NF-kappaB-activating and apoptosis-inducing proteins of the TNF
      receptor complex.
AB  - The cytokine tumor necrosis factor (TNF) elicits a wide range of biological
      responses, including inflammation, cell proliferation, differentiation, and
      apoptosis. Although the molecular mechanisms of TNF signaling have been largely
      elucidated, the principle that regulates the balance of life and death is still
      unknown. This review will focus on the crosstalk that exists between proteins of
      the TNF receptor (TNF-R) signalosome, and which are involved in the initiation of
      nuclear factor kappa B (NF-kappaB) activation or apoptosis. At least four
      different mechanisms of regulation can be distinguished: (i) NF-kappaB-mediated
      induction of proteins of the TNF-R complex; (ii) NF-kappaB-independent protection
      against apoptosis by the TNF-R-associating factor 2 (TRAF2)-mediated recruitment
      of antiapoptotic proteins; (iii) dual activation of apoptosis and NF-kappaB by a
      single molecule; and (iv) amplification of the death signal by proteolytic
      inactivation of signaling proteins that are involved in NF-kappaB activation or
      cell survival.

PMID- 11529676
TI  - The chicken RelB transcription factor has transactivation sequences and a tissue
      specific expression pattern that are distinct from mammalian RelB.
AB  - Rel/NF-kappaB proteins are eukaryotic transcription factors that control the
      expression of genes involved in a large variety of cellular processes. Rel
      proteins share a highly conserved DNA-binding/dimerization domain called the Rel
      Homology (RH) domain. We have constructed and characterized a composite cDNA
      encoding most of the chicken RelB transcription factor. The predicted chicken
      RelB protein has a high degree of sequence similarity to other vertebrate RelB
      proteins within the RH domain, but is much less conserved outside this domain.
      Chicken RelB does not bind DNA as a homodimer, but forms DNA-binding heterodimers
      with NF-kappaB p50 or p52. Overexpressed chicken RelB localizes to the nucleus in
      chicken embryo fibroblasts, and the nonconserved C-terminal sequences of chicken
      RelB contain a transactivation domain that functions in chicken and mouse
      fibroblasts. Thus, chicken RelB has functional properties similar to other
      vertebrate RelB proteins. However, Western blotting of diverse chicken tissues
      indicates that chicken RelB is more widely expressed than mammalian RelB.

PMID- 11529677
TI  - Phosphorylation of histones triggers DNA fragmentation in thymocyte undergoing
      apoptosis induced by protein phosphatase inhibitors.
AB  - The treatment of thymocytes with protein phosphatase inhibitors such as calyculin
      A and okadaic acid resulted in apoptosis with a concomitant increase in
      phosphorylation of nuclear proteins. The phosphorylated protein in the thymocyte
      nuclei induced by protein phosphatase inhibitors was identified as histones by
      the use of two-dimensional polyacrylamide gel electrophoresis. These compounds
      accelerated the phosphorylation of histone H2A, H3, and H1. On the other hand,
      little phosphorylation of H2B and H4 by these compounds was observed. The effect
      of these compounds on the level of nuclear histones was also examined using high
      performance capillary electrophoresis. No significant changes in the level of
      histones were seen in the nuclei of thymocytes treated with calyculin A and
      okadaic acid. Thus, the induction of thymocyte apoptosis is involved in the
      chemical modification of histones but not the change in their quantity. Moreover,
      the treatment of thymocytes with calyculin A increased the sensitivity toward
      endogenous DNase in the nuclei. These results suggest that phosphorylation of
      histones, especially H2A, H3, and H1, is an early step of triggering DNA
      fragmentation in thymocyte apoptosis.

PMID- 11529678
TI  - An intramolecular contact in Galpha transducin that participates in maintaining
      its intrinsic GDP release rate.
AB  - Receptor mediated stimulation of the G protein-alpha subunit leads to exchange of
      GDP for GTP, activating the protein. Spontaneous GDP release from Galpha can also
      lead to the active state, if GTP in solution binds the nucleotide binding pocket.
      The purpose of this study is to evaluate the molecular determinants for
      maintaining the spontaneous GDP release rates between two Galpha subunits.
      Galpha(t) has a low rate of nucleotide release, compared to Galpha(i1).
      Galpha(t/i1) chimeras were used to explore the molecular basis for this behavior.
      The C-terminal alpha4-helix, the N-terminal 56 residues and the Switch I/II
      regions of Galpha(t) were shown to affect the low spontaneous GDP release rate in
      Galpha(t). A specific molecular contact between Asp26 and Asn191 was found in
      Galpha(t) that is not present in Galpha(i1). In two chimeras disrupting this
      interaction produced an increased spontaneous GDP release; restoring the contact
      present in Galpha(t) into these chimeras decreased the GDP release rate by half
      as compared to the original chimeras. Similarly, introduction of this contact in
      wild-type Galpha(i1) decreased the GDP release rate of Galpha(i1) by half.
      Differences in GDP release rates may reflect physiological roles these proteins
      play in living systems.

PMID- 11529679
TI  - Involvement of conserved hydrophobic residues in the CTLD of human lectin-like
      oxidized LDL receptor in ligand binding.
AB  - We previously identified the hydrophilic residues that are essential for ligand
      binding in the C-type lectin-like domain (CTLD) of human lectin-like oxidized LDL
      receptor (hLOX-1). To provide a more detailed understanding of ligand binding, we
      selected in the present study 13 conserved hydrophobic residues in the CTLD of
      hLOX-1 for mutagenesis analysis. The selected residues were replaced either by
      Ser (drastic mutation) or by size- and structure-based alternative hydrophobic
      residues (conserved mutation). Mutation targeted at F228, Y238, and G232 deprived
      hLOX-1 of ligand binding without alteration of protein expression and
      localization. In contrast, drastic mutation introduced into positions W203, W215,
      and W217 resulted in mislocalization, whereas conserved mutation at the same
      sites resulted in clones with similar cell surface localization and ligand
      binding to native hLOX-1. Our results indicate that F228, Y238, and G232 are
      essential for ligand binding, while W203, W215, W217, and L206 play a structural
      role.

PMID- 11529680
TI  - A mutation in the yeast mitochondrial ribosomal protein Rml2p is associated with
      a defect in catalase gene expression.
AB  - Yeast strains containing a new temperature-sensitive allele of the RML2 gene,
      encoding a component of the large subunit of the mitochondrial ribosome, display
      normal growth on acetate, slowed growth on glycerol and an inability to grow on
      oleic acid. These cells, denoted rml2(fat21), have an apparent inability to
      induce peroxisomal function, as evidenced by a deficiency in oleic acid induction
      of beta-oxidation. However, the oleic acid regulation of genes encoding core
      enzymes of peroxisomal beta-oxidation is normal. In contrast, up-regulation of
      CTA1 (catalase) mRNA expression and enzyme activity is interrupted. Upon
      comparison of the induction requirements of catalase and the genes of beta
      oxidation, we hypothesized that the rml2(fat21) mutation alters the activity of
      the transcription factor Adr1p. In support of this hypothesis, over-expression of
      ADR1 in rml2(fat21) cells restores CTA1 induction. Several assays of mitochondria
      from rml2(fat21) strains suggest normal mitochondrial function. Thus, the
      modulation of Adr1p-associated gene regulation is not due to overt mitochondrial
      dysfunction.

PMID- 11529681
TI  - Participation of intracellular Ca(2+)/calmodulin and protein kinase(s) in the
      pathway of apoptosis induced by a Drosophila cell death gene, reaper.
AB  - To elucidate the apoptotic signaling pathway, we have generated a cell culture
      model: S2 cells stably transfected with a Drosophila cell death gene, reaper
      (rpr). Following rpr overexpression, caspase activation-mediated apoptotic cell
      death was induced in the cells. Apoptosis triggered by rpr required intracellular
      Ca(2+) ions and calmodulin. Furthermore, protein kinase inhibitors H-7 (a PKC,
      PKA, PKG, MLCK, and CKI inhibitor), calphostin C (a PKC inhibitor), or H-89 (a
      PKA and PKG inhibitor) completely blocked apoptosis induced by rpr, suggesting
      that some kind of serine/threonine protein kinase(s) act upstream of caspase in
      apoptotic pathway induced by rpr in S2 cells.

PMID- 11529682
TI  - Cloning and tissue-specific gene expression studies with Dlxin-1, a newly
      identified transcriptional activator.
AB  - Dlxin-1, a unique member of the necdin/melanoma associated antigen gene (MAGE)
      family, is a novel protein that binds Dlxin-5 and regulates its transcriptional
      function. We have cloned the homology region between Dlxin-1 and necdin from
      mouse melanoma cells. Here we report the expression cloning, characterization,
      and detailed tissue-specific expression studies of Dlxin-1. A unique expression
      pattern of Dlxin-1 emerged from the work wherein strong expression of a 3.2-Kb
      transcript was observed in mouse brain and embryos. Amongst the representative
      established cell lines of different tumor categories studied the presence of
      transcript was detected only in sarcomas and neuroectodermal tumors.
      Characteristically, lymphomas, leukaemias, adenocarcinomas, and carcinomas did
      not express Dlxin-1. Also, we observed a growth suppression on ectopic expression
      of this cDNA possibly due to the close homology shared with necdin, a neuron
      specific growth suppressor. The extensive homology of our Dlxin-1 clone to necdin
      makes it an attractive system to understand the importance of the necdin/MAGE
      family of molecules in cell cycle regulation.

PMID- 11529683
TI  - PET in psychopharmacology.
AB  - Emission tomography techniques and, in particular, positron emission tomography
      (PET) enable the in vivo study of several physiological and neurochemical
      variables in human subjects using methods originally developed for quantitative
      autoradiography. In particular, PET allows one to evaluate in human subjects: (a)
      the effect of specific neurochemical challenges on regional brain function at
      rest or under activation; (b) the activity of neurotransmitters and the regional
      expression of specific molecular targets during pathology including their
      modulation by drug treatment; (c) the kinetics of drug disposition and activity
      directly in the target organ. This is of primary interest in the field of
      biological psychiatry and in psychoactive drugs development, where it is
      particularly difficult to reproduce human diseases using animal models in view of
      the peculiarity of this field and the large heterogeneity of each psychiatric
      illness also inside the same clinical definition. The aim of this paper is to
      review the principal strategies and the main results of the use of PET in
      psychopharmacology.

PMID- 11529684
TI  - Muscarinic receptors in the mammalian heart.
AB  - In the mammalian heart, cardiac function is under the control of the sympathetic
      and parasympathetic nervous system. All regions of the mammalian heart are
      innervated by parasympathetic (vagal) nerves, although the supraventricular
      tissues are more densely innervated than the ventricles. Vagal activation causes
      stimulation of cardiac muscarinic acetylcholine receptors (M-ChR) that modulate
      pacemaker activity via I(f) and I(K.ACh), atrioventricular conduction, and
      directly (in atrium) or indirectly (in ventricles) force of contraction. However,
      the functional response elicited by M-ChR-activation depends on species, age,
      anatomic structure investigated, and M-ChR-agonist concentration used. Among the
      five M-ChR-subtypes M(2)-ChR is the predominant isoform present in the mammalian
      heart, while in the coronary circulation M(3)-ChR have been identified. In
      addition, evidence for a possible existence of an additional, not M(2)-ChR in the
      heart has been presented. M-ChR are subject to regulation by G-protein-coupled
      receptor kinase. Alterations of cardiac M(2)-ChR in age and various kinds of
      disease are discussed.

PMID- 11529685
TI  - Aescin: pharmacology, pharmacokinetics and therapeutic profile.
AB  - Aescin, the major active principle from Aesculus hippocastanum (Hippocastanaceae)
      the horse chestnut tree, has shown satisfactory evidence for a clinically
      significant activity in chronic venous insufficiency (CVI), haemorrhoids and post
      operative oedema. In one controlled trial aescin was shown to be as effective as
      compression therapy as an alternative to medical treatment for CVI. The
      therapeutic benefit is well supported by a number of experimental investigations
      in different animal models, indicative of clearcut anti-oedematous, anti
      inflammatory and venotonic properties, mainly related to the molecular mechanism
      of the agent, allowing improved entry of ions into channels, thus raising venous
      tension in both in vitro and in vivo conditions. Other mechanisms, i.e. release
      of PGF(2) from veins, antagonism to 5-HT and histamine, reduced catabolism of
      tissue mucopolysaccharides, further underline the wide ranging mechanisms of the
      therapeutic activity of aescin. The excellent tolerability of aescin in the
      clinic indicates this treatment is of definite clinical benefit in patients with
      clinical conditions resulting in CVI, haemorrhoids or peripheral oedema
      formation.

PMID- 11529686
TI  - Alpha-adrenoceptor subtypes.
AB  - Different studies have led to our present knowledge of the membrane receptors
      responsible for mediating the responses to the endogenous catecholamines. These
      receptors were initially differentiated into alpha - and beta-adrenoceptors.
      Alpha-adrenoceptors mediate most excitatory functions, and were in turn
      differentiated in the 1970s into alpha(1)- and alpha(2)-adrenoceptors. The
      alpha(1)-adrenoceptor type usually mediates responses in the effector organ. The
      alpha(2)-adrenoceptor type is located presynaptically and regulates the release
      of the neurotransmitter but it is also present in postsynaptical locations. Both
      alpha-adrenoceptors are important for the control of vascular tone, but we now
      know that neither alpha(1)- nor alpha(2)-adrenoceptors constitute homogeneous
      groups. Each alpha-adrenoceptor type can be subdivided into different subtypes
      and in this review we have turned our attention to these. The alpha(1)- and the
      alpha(2)-adrenoceptor subtypes were previously defined pharmacologically by
      functional and binding studies, and later they were also isolated and identified
      using cloning methods. In fact, the study of alpha-adrenoceptors was
      revolutionized by the techniques of molecular biology which permitted us to
      establish the present classification. The present classification of alpha(1)
      adrenoceptors stands as follows: alpha(1A)-adrenoceptor subtype (cloned alpha(1c)
      and redesignated alpha(1a/c)), alpha(1B)-adrenoceptor subtype (cloned alpha(1b))
      and alpha(1D)-adrenoceptor subtype (cloned alpha(1d) and redesignated
      alpha(1a/d)). It has not been easy to establish the distribution of these
      alpha(1)-adrenoceptor subtypes in the various organs and tissues, or to define
      the functional response mediated by each one in the different species studied.
      Nevertheless it seems that the alpha(1A)-adrenoceptor subtype is more implicated
      in the maintenance of vascular basal tone and of arterial blood pressure in
      conscious animals, and the alpha(1B)-adrenoceptor subtype participates more in
      responses to exogenous agonists. It has also been observed that the expression of
      the alpha(1B)-adrenoceptor subtype can be modified in pathological situations and
      particular attention has been paid to the regulation of expression of this
      receptor. The present classification of alpha(2)-adrenoceptors stands as follows:
      alpha(2A/D)-adrenoceptor subtype (today it is accepted that the alpha(2A)
      adrenoceptor subtype and the alpha(2D)-adrenoceptor subtype are the same receptor
      but they were identified in different species: the alpha(2A) in human and the
      alpha(2D) in rat); alpha(2B)-adrenoceptor subtype (cloned alpha(2b)) and
      alpha(2C)-adrenoceptor subtype (cloned alpha(2c)). Today we know that the
      alpha(2A/D)- and alpha(2B)-adrenoceptor subtypes in particular control arterial
      contraction, and that the alpha(2C)-adrenoceptor subtype is responsible above all
      for venous vasoconstriction. We also know that the alpha(2 A/D)-adrenoceptor
      subtype fundamentally mediates the central effects of the alpha(2)-adrenoceptor
      agonists. Despite the validity of the above-mentioned classification of the
      alpha(1)- and alpha(2)-adrenoceptors, it seems clear that the contractions of a
      large number of tissues including smooth muscle are mediated by more than one
      alpha-adrenoceptor subtype. Moreover, few ligands recognise only one alpha
      adrenoceptor subtype and the lack of specifity in the different drugs for each
      one limits their administration in vivo and their therapeutic use.

PMID- 11529687
TI  - Influence of an abrupt increase in blood pressure on the blood-brain barrier
      permeability during acute hypertension and epileptic seizures.
AB  - The interrelationship between the breakdown of the blood-brain barrier according
      to the Evans-blue passage and an abrupt increase in blood pressure (DeltaP) was
      studied in rats subjected to adrenaline-induced acute hypertension and also
      pentylenetetrazol-induced seizures. Arterial blood pressure was increased by
      adrenaline, then immediately i.v. nifedipine was injected and subsequently
      decreased to the control value in the acute hypertensive group. Arterial blood
      pressure was increased by pentylenetetrazol, then immediately GABA (gamma
      aminobutiric acid) was injected and the blood pressure was decreased to the
      control value in the seizure group. The animals were divided into five groups.
      Group I: control; Group II: acute hypertension; Group III: acute hypertension +
      nifedipine; Group IV: seizure; Group V: seizure + GABA. The Evans-blue dye
      content was found to be 0.25 +/- 0.01 mg% in the whole brain in the control
      animals, and 0.803 +/- 0.1 mg% in the acute hypertensive group. This difference
      between these groups was found to be significant: P< 0.01. In the nifedipine
      group (Group III) the Evans-blue content was 0.30 +/- 0.1 mg% in the whole brain;
      and there was no significant difference between control values and nifedipine
      treated animals (P> 0.5). The Evans-blue content was 1.6 +/- 0.2 mg% in the whole
      brain during seizure, and decreased to 0.36 +/- 0.1 mg% after GABA injection was
      administered. There was also no significant difference between the control value
      and the GABA-treated animals (P> 0.5). These results have shown that an abrupt
      increase in blood pressure (DeltaP) did not change the blood-brain barrier
      permeability in both acute hypertension and seizures.

PMID- 11529688
TI  - Anti-inflammatory activities of LDP-392, a dual PAF receptor antagonist and 5
      lipoxygenase inhibitor.
AB  - Leukotrienes (LTs) and platelet-activating factor (PAF) are important mediators
      of inflammation and allergy. LDP-392, a novel dual PAF receptor antagonist and 5
      lipoxygenase (5-LO) inhibitor, has been identified. LDP-392 is 17.9-fold more
      potent than zileuton (5-LO inhibitor) in the RBL cytosolic 5-LO assay, and
      equally potent as MK 287 (PAF receptor antagonist) in the human platelet PAF
      receptor binding assay. The in vivo dual activities of LDP-392 were confirmed by
      measuring the inhibition of ex vivo LTB(4)production in rats and PAF-induced
      hemoconcentration in mice. Intravenous administration of LDP-392 demonstrated
      greater inhibition than zileuton, BN 50739 or MK 287 on arachidonic acid-induced
      ear edema and protected mice from LPS-induced lethality. Topical administration
      of LDP-392, in a dose-dependent manner, inhibited TPA-induced ear edema in mice
      and UVB-induced erythema in guinea-pigs. These data suggest that LDP-392, as a
      dual PAF receptor antagonist and 5-LO inhibitor, may be of greater clinical
      effectiveness.

PMID- 11529689
TI  - Involvement of nitric oxide in non-adrenergic non-cholinergic relaxation and
      action of vasoactive intestinal polypeptide in circular muscle strips of the rat
      gastric fundus.
AB  - We examined the characteristics of the non-adrenergic non-cholinergic (NANC)
      nerve induced relaxation and the possible interaction between nitric oxide (NO)
      and vasoactive intestinal polypeptide (VIP) on the basal tone of the circular
      muscle of the rat gastric fundus. Electrically induced NANC relaxations were
      partly inhibited by N(omega)-nitro-L-arginine (100 microM), whereas sodium
      nitroprusside (SNP; 10 microM) and VIP (5 nM) induced relaxations were not
      affected. 2-Amino-5,6-dihydro-6-methyl-4H-1,3-thiazine (AMT; 5 microM) also
      inhibited the responses to electrical stimuli to a similar extent as N(omega)
      nitro-L-arginine but not VIP. However, AMT plus N(omega)-nitro-L-arginine did not
      give an additional inhibition above that of each drug alone on NANC relaxations,
      and dexamethasone (10 microM) had no effect on NANC nerve induced relaxations. 1H
      [1,2,4,]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 10 microM), a selective inhibitor
      of guanylate cyclase, abolished the responses to NANC nerve stimulation and SNP,
      while VIP responses were not influenced. N-ethylmaleimide (100 microM), an
      adenylate cyclase inhibitor, attenuated relaxations to NANC nerve stimulation,
      VIP and isoproterenol (1 nM), while having no effect on those to SNP, but in
      combination with N(omega)-nitro-L-arginine, there was no additional inhibition on
      the responses to nerve stimulation. Alpha-chymotrypsin (10 u ml(-1)) severely
      diminished VIP induced relaxations, but did not reduce electrical responses. In
      conclusion, these results suggest that NO is involved in the relaxations induced
      by short-term electrical stimulation. However, another possible unidentified
      transmitter that can trigger the accumulation of cyclic GMP is not entirely ruled
      out and there is no interaction between NO and VIP in the circular muscle strip
      of the rat gastric fundus, even in the basal state of the tissue.

PMID- 11529690
TI  - Biphenylacetic acid enhances the antagonistic action of fluoroquinolones on the
      GABA(A)-mediated responses of the isolated guinea-pig ileum.
AB  - This paper examines the effect of biphenylacetic acid on the antagonistic action
      of norfloxacin and enoxacin on the GABA(A)-mediated responses of the isolated
      guinea-pig ileum. GABA produced transient contractions followed by relaxation.
      The contractile effect of exogenously applied GABA was concentration-dependent
      with EC(50)= 9.8 x 10(-6) M. This contractile effect was not significantly
      modified by biphenylacetic acid, and the EC(50) value for GABA in the presence of
      10(-5) M biphenylacetic acid was 1.15 x 10(-5) M. The GABA contractile effect was
      inhibited, dose-dependently, by either norfloxacin or enoxacin, but only at
      concentrations higher than 10(-5) M. The response of the ileum to GABA (at
      EC(50)) was reduced to 35 and 36% by pretreatment with 10(-5) M norfloxacin or
      enoxacin, respectively. However, in the presence of 10(-5) M biphenylacetic acid,
      the response of the ileum to GABA was reduced to 2.2% by pretreatment with 10(-5)
      M enoxacin, while it was completely abolished by pretreatment with 10(-5) M
      norfloxacin and the IC(50) values were 5.5 x 10(-7) and 1.5 x 10(-6) M for
      norfloxacin and enoxacin, respectively. These data show that biphenylacetic acid
      whilst having no effect at the GABA(A)-mediated contractile response of the
      guinea-pig ileum, enhances the antagonistic effect of both enoxacin and
      norfloxacin. This suggests that combined administration of fluoroquinolones and
      biphenylacetic acid synergistically inhibits GABA(A)-receptors at the intestinal
      level.

PMID- 11529691
TI  - L-carnitine prevents the progression of atherosclerotic lesions in
      hypercholesterolaemic rabbits.
AB  - This study has been initiated to investigate, in hypercholesterolaemic rabbits,
      whether L-carnitine deficiency could be an additional risk factor in
      atherosclerosis, and if so, whether L-carnitine supplementation could prevent the
      progression of atherosclerosis. Hypercholesterolaemia was induced by feeding
      rabbits 2% cholesterol-enriched diet for 28 days, whereas, carnitine deficiency
      was induced by daily i.p. administration of 250 mg kg(-1) of D-carnitine for 28
      days. Histopathological examination of aorta and coronaries from
      hypercholesterolaemic rabbits revealed severe atherosclerotic lesions, intimal
      plaques and foam cell formation. Also, hypercholesterolaemic diet resulted in a
      significant 53 and 43% decrease in reduced glutathion (GSH) levels and a
      significant (1.87-fold) and (14.1-fold) increase in malonedialdhyde (MDA) levels
      in aorta and cardiac tissues, respectively. Daily administration of L-carnitine
      (250 mg kg(-1)) for 28 days, completely prevented the progression of
      atherosclerotic lesions induced by hpercholesterolaemia in both aorta and
      coronaries. Conversely, daily administration of D-carnitine (250 mg kg(-1)) for
      28 days increased the progression of atherosclerotic lesions with the appearance
      of foam cells and apparent intimal plaques which are even larger than that seen
      in hypercholesterolaemic rabbits. Both L-carnitine and D-carnitine produced
      similar effects on the lipid profile, GSH and MDA which may point to the
      conclusion that: (1) L-carnitine prevents the progression of atherosclerotic
      lesions by another mechanism in addition to its antioxidant and lipid-lowering
      effects; (2) endogenous carnitine depletion and/or carnitine deficiency should be
      viewed as an additional risk factor in atherogenesis.

PMID- 11529692
TI  - Photodynamic activity of the haematoporphyrin derivative with rutin and arginine
      substituents (HpD-Rut(2)-Arg(2)) against Staphylococcus aureus and Pseudomonas
      aeruginosa.
AB  - The impact of the new photosensitizer HpD-Rut(2)-Arg(2)on the growth of
      methicillin-resistant Staphylococcus aureus(MRSA), methicillin-susceptible
      Staphylococcus aureus (MSSA) and Pseudomonas aeruginosa clinical strains isolated
      from infected burn wounds was examined. The susceptibility of the isolates to the
      photodynamic action of the sensitizer was evaluated by the determination of
      minimal inhibitory concentration (MIC) and minimal bactericidal concentration
      (MBC) using the newly developed microdilution method. The results were compared
      with the previously investigated HpD-Arg(2). All clinical isolates examined
      proved to be susceptible to the photodynamic action of HpD-Rut(2)-Arg(2). The MIC
      of this newly synthetized photosensitizer ranged from 0.8 to 12.5 microg ml(-1)
      for MRSA, from 0.4 to 6.2 microg ml(-1) for MSSA and from 6.2 to 50 microg ml(-1)
      for P. aeruginosa. While MBC ranged from 1.6 to 12.5 microg ml(-1) for MRSA, 0.4
      to 6.2 microg ml(-1) for MSSA and 6.2 to 100 microg ml(-1) for P. aeruginosa.
      This photosensitizer is more effective in its bactericidal photodynamic action
      than previously tested HpD-Arg(2).

PMID- 11529693
TI  - Pharmacokinetic study of iodine-labeled silibinins in rat.
AB  - The very low bioavailability of silibinin (silybin, SB), the main antioxidant
      flavonolignan of silymarin from Silybum marianum L. (Asteraceae), requires
      sensitive methods to study the modulation of silibinin bioavailability. To
      evaluate the potential for use of radiolabeled silibinin, two silibinin
      derivatives, separated by HPLC after iodination ((125)I-SB(1) and (125)I-SB(2))
      and their complexes 1 : 1 with phosphatidylcholine ((125)I-SPC(1) and (125)I
      SPC(2)) were administered concurrently with a single intragastric dose of 5.0 mg
      or 50 mg of unlabeled silibinin (alone or as a constituent of the complex) per kg
      of body weight in a comparative study of bioavailability in the rat.
      Pharmacokinetic parameters as well as organ uptake of (125)I-SB(1)-derived
      radioactivity showed a dose-response pattern. The parameters of bioavailability
      after (125)I-SPC(1) intake were not influenced by unlabeled silibinin (complexed
      with phosphatidylcholine), since maximal levels were achieved by the lower dose
      of unlabeled compound. The superior bioavailability of (125)I-SPC(1) was obvious
      at the lower dose of unlabeled compound as elevated AUC and RA(max) (maximal
      percentage of administered radioactivity), and increased radioactivity in liver,
      kidney, spleen and heart. An absence of these characteristics with (125)I-SB(2)
      and (125)I-SPC(2) suggests the use of(125)I-SB(1) for studies of modulation of
      its bioavailability in vivo in rat.

PMID- 11529694
TI  - Restricted activity among community-living older persons: incidence,
      precipitants, and health care utilization.
AB  - BACKGROUND: Restricted activity is a potentially important indicator of health
      and functional status. Yet, relatively little is known about the incidence,
      precipitants, or health care utilization associated with restricted activity
      among older persons. OBJECTIVE: To more accurately estimate the rate of
      restricted activity among community-living older persons, to identify the health
      related and non-health-related problems that lead to restricted activity, and to
      determine whether restricted activity is associated with increased health care
      utilization. DESIGN: Prospective cohort study. SETTING: New Haven, Connecticut.
      PARTICIPANTS: 754 nondisabled members of a large health plan, 70 years of age or
      older, who were categorized according to their risk for disability (low,
      intermediate, or high). MEASUREMENTS: Occurrence of restricted activity (defined
      as having stayed in bed for at least half a day or having cut down on one's usual
      activities because of an illness, injury, or another problem), problems leading
      to restricted activity, and health care utilization were ascertained during
      monthly telephone interviews for up to 2 years. RESULTS: In median follow-up of
      15 months, 76.6% of participants reported restricted activity during at least 1
      month and 39.3% reported restricted activity during 2 consecutive months. The
      rates of restricted activity per 100 person-months were 19.0 episodes for all
      participants and 16.9, 27.3, and 22.7 episodes for participants at low,
      intermediate, and high risk for disability, respectively. Of the 24 prespecified
      health-related and non-health-related problems, the rates per 100 person-months
      of restricted activity ranged from 0.1 episode for "problem with alcohol" to 65.5
      episodes for "been fatigued." On average, participants identified 4.5 different
      problems as a cause for their restricted activity. Health care utilization was
      substantially greater during months with restricted activity than months without
      restricted activity. The corresponding rates per 100 person-months were 63.8 and
      45.1 for physician office visits, 12.5 and 1.0 for emergency department visits,
      14.1 and 0.3 for hospital admissions, and 67.6 and 45.1 for any health care
      utilization (P < 0.001 for each pairwise comparison). CONCLUSIONS: Restricted
      activity is common among community-living older persons, regardless of risk for
      disability, and it is usually attributable to several concurrent health-related
      problems. Although restricted activity is associated with a substantial increase
      in health care utilization, older persons with restricted activity often do not
      seek medical attention.

PMID- 11529695
TI  - A prospective study of asymptomatic carriers of the factor V Leiden mutation to
      determine the incidence of venous thromboembolism.
AB  - BACKGROUND: The factor V Leiden mutation is a common genetic defect associated
      with an increased risk for venous thromboembolism. The clinical implications for
      asymptomatic carriers of this mutation and, consequently, the usefulness of
      screening families in which a proband has both the mutation and venous
      thromboembolism are unclear. OBJECTIVE: To determine the incidence of venous
      thromboembolism in asymptomatic carriers of the factor V Leiden mutation. DESIGN:
      Prospective cohort study. SETTING: University hospitals in the Netherlands.
      PARTICIPANTS: 470 asymptomatic carriers of the factor V Leiden mutation (234 men,
      236 women; mean age, 43 years [range, 15 to 88 years]), 12 of whom were
      homozygous. Carriers were identified by screening the first-degree relatives (>15
      years of age) of 247 symptomatic probands. MEASUREMENTS: Objectively diagnosed
      episodes of venous thromboembolism and the relationship between incidence and
      exposure to high-risk situations. RESULTS: Nine venous thromboembolic events were
      observed in 1564 observation-years, resulting in an annual incidence of 0.58%
      (95% CI, 0.26% to 1.10%). The incidence of spontaneous venous thromboembolism was
      0.26% (CI, 0.07% to 0.65%) per year; 3.5% (CI, 0.1% to 17.8%) per episode of
      surgery, trauma, or immobilization; 0.0% (CI, 0.0% to 19.5%) per pregnancy; 1.8%
      (CI, 0.4% to 5.2%) per year of oral contraceptive use; and 2.9% (CI, 0.8% to
      15.3%) per year of use of hormone replacement therapy. CONCLUSIONS: The absolute
      annual incidence of spontaneous venous thromboembolism in asymptomatic carriers
      of the factor V Leiden mutation is low and does not justify routine screening of
      the families of symptomatic patients.

PMID- 11529696
TI  - Racial differences in cardiac revascularization rates: does "overuse" explain
      higher rates among white patients?
AB  - BACKGROUND: Coronary artery bypass graft (CABG) surgery and percutaneous
      transluminal coronary angioplasty (PTCA) are well-established treatments for
      symptomatic coronary artery disease. Previous studies have documented racial
      differences in rates of use of these cardiac revascularization procedures. Other
      studies suggest that these procedures are overused: that is, they are done for
      patients with clinically inappropriate indications. OBJECTIVE: To test the
      hypothesis that the higher rate of cardiac revascularization among white patients
      is associated with a higher prevalence of overuse (revascularization for
      clinically inappropriate indications) among white patients than among African
      American patients. DESIGN: Observational cohort study using Medicare claims and
      medical record review. SETTING: 173 hospitals in five U.S. states. PARTICIPANTS:
      A stratified, weighted, random sample of 3960 Medicare beneficiaries who
      underwent coronary angiography during 1991 and 1992; 1692 of these patients
      underwent 1711 revascularization procedures within 90 days. MEASUREMENTS: The
      proportion of CABG and PTCA procedures rated appropriate, uncertain, and
      inappropriate according to RAND criteria, and the multivariate odds of undergoing
      inappropriate revascularization among African-American patients and white
      patients. RESULTS: After angiography, rates of PTCA (23% vs. 19%) and CABG
      surgery (29% vs. 17%) were significantly higher among white patients than among
      African-American patients. The respective rates of inappropriate PTCA and CABG
      surgery were 14% and 10%. Among the study states, rates of inappropriate use
      ranged from 4% to 24% for PTCA and 0% to 14% for CABG surgery. White patients
      were more likely than African-American patients to receive inappropriate PTCA
      (15% vs. 9%; difference, 6 percentage points [95% CI, -0.4 to 12.7 percentage
      points]), and difference by race was statistically significant among men (20% vs.
      8%; difference, 12 percentage points [CI, 1.2 to 21.7 percentage points]). Rates
      of inappropriate CABG surgery did not differ by race (10% in both groups).
      CONCLUSIONS: Among a large and diverse sample of Medicare beneficiaries in five
      U.S. states, overuse of PTCA was greater among white men than among other groups,
      but this difference did not fully account for racial disparities in
      revascularization. Overuse of cardiac revascularization varied significantly by
      geographic region.

PMID- 11529697
TI  - Molecular analysis of the mevalonate kinase gene in a cohort of patients with the
      hyper-igd and periodic fever syndrome: its application as a diagnostic tool.
AB  - BACKGROUND: The hyper-IgD and periodic fever syndrome (HIDS) is characterized by
      recurrent attacks of fever, abdominal distress, and arthralgia and is caused by
      mevalonate kinase mutations. OBJECTIVE: To ascertain the role of mevalonate
      kinase and the usefulness of molecular diagnosis in HIDS. DESIGN: Cross-sectional
      study. SETTING: The international Nijmegen HIDS registry. PATIENTS: 54 patients
      from 41 families who met the clinical criteria for HIDS. MEASUREMENTS: Clinical
      symptoms and signs, immunoglobulin concentration, leukocyte count, erythrocyte
      sedimentation rate, mutation analysis, and mevalonate kinase enzyme activity
      assay. RESULTS: There were two groups of patients: 41 patients with mevalonate
      kinase mutations (classic-type HIDS) and 13 patients without mutations (variant
      type HIDS). Patients with classic-type HIDS had a lower mevalonate kinase enzyme
      activity, a higher IgD level, and more additional symptoms with attacks. The IgD
      level did not correlate with disease severity, mevalonate kinase enzyme activity,
      or genotype. CONCLUSION: Genetic heterogeneity exists among patients with a
      clinical diagnosis of HIDS.

PMID- 11529698
TI  - Perceptions about complementary therapies relative to conventional therapies
      among adults who use both: results from a national survey.
AB  - BACKGROUND: Little is known about perceptions of complementary and alternative
      medical (CAM) therapy relative to conventional therapy among patients who use
      both. OBJECTIVE: To document perceptions about CAM therapies among persons who
      use CAM and conventional therapies. DESIGN: Nationally representative, random
      household telephone survey. SETTING: The 48 contiguous U.S. states. PARTICIPANTS:
      831 adults who saw a medical doctor and used CAM therapies in 1997. MEASUREMENTS:
      Perceptions about helpfulness and patterns of CAM therapy use relative to
      conventional therapy use and reasons for nondisclosure of CAM therapies. RESULTS:
      Of 831 respondents who saw a medical doctor and used CAM therapies in the
      previous 12 months, 79% perceived the combination to be superior to either one
      alone. Of 411 respondents who reported seeing both a medical doctor and a CAM
      provider, 70% typically saw a medical doctor before or concurrent with their
      visits to a CAM provider; 15% typically saw a CAM provider before seeing a
      medical doctor. Perceived confidence in CAM providers was not substantially
      different from confidence in medical doctors. Among the 831 respondents who in
      the past year had used a CAM therapy and seen a medical doctor, 63% to 72% did
      not disclose at least one type of CAM therapy to the medical doctor. Among 507
      respondents who reported their reasons for nondisclosure of use of 726
      alternative therapies, common reasons for nondisclosure were "It wasn't important
      for the doctor to know" (61%), "The doctor never asked" (60%), "It was none of
      the doctor's business" (31%), and "The doctor would not understand" (20%). Fewer
      respondents (14%) thought their doctor would disapprove of or discourage CAM use,
      and 2% thought their doctor might not continue as their provider. Respondents
      judged CAM therapies to be more helpful than conventional care for the treatment
      of headache and neck and back conditions but considered conventional care to be
      more helpful than CAM therapy for treatment of hypertension. CONCLUSIONS:
      National survey data do not support the view that use of CAM therapy in the
      United States primarily reflects dissatisfaction with conventional care. Adults
      who use both appear to value both and tend to be less concerned about their
      medical doctor's disapproval than about their doctor's inability to understand or
      incorporate CAM therapy use within the context of their medical management.

PMID- 11529699
TI  - Racial differences in the use of invasive cardiovascular procedures: review of
      the literature and prescription for future research.
AB  - PURPOSE: The cause of racial disparities in the use of invasive cardiac
      procedures remains unclear. To summarize, evaluate, and clarify gaps in the
      literature, studies examining racial differences in cardiac catheterization,
      percutaneous transluminal coronary angioplasty (PTCA), and coronary artery bypass
      grafting (CABG) were reviewed. DATA SOURCES: MEDLINE search for English-language
      articles published from 1966 to May 2000. STUDY SELECTION: Empirical studies of
      adults. DATA EXTRACTION: The odds ratios for procedure use by race were examined
      for each study; cohorts and covariates were also documented. DATA SYNTHESIS:
      Literature was classified as one of three groups on the basis of study design.
      For the first group, which used administrative data, odds ratios (ORs) for
      African-American patients compared with white patients ranged from 0.41 to 0.94
      for cardiac catheterization, from 0.32 to 0.80 for PTCA, and from 0.23 to 0.68
      for CABG. Procedure rates were also lower for Hispanic and Asian patients. In the
      second group, which used detailed clinical data, African-American patients
      remained disproportionately less likely to receive cardiac catheterization (OR,
      0.03 to 0.85), PTCA (OR, 0.20 to 0.87), and CABG (OR, 0.22 to 0.68). A few
      studies noted that Hispanic and Asian patients were also disproportionately less
      likely to receive such procedures. The third group used survey methods but found
      conflicting results regarding patient refusals as a source of racial variation.
      Less-educated patients and patients who were not as experienced with the
      procedure were more likely to decline PTCA. Physician bias was also associated
      with racial variation in recommendations for treatment. CONCLUSIONS: Racial
      differences in invasive cardiac procedure use were found even after adjustment
      for disease severity. Future studies should comprehensively and simultaneously
      examine the full range of patient, physician, and health care system variables
      related to racial differences in the provision of invasive cardiac procedures.

PMID- 11529700
TI  - The thrombophilias: well-defined risk factors with uncertain therapeutic
      implications.
AB  - Discovery of the factor V Leiden and prothrombin G20210A mutations has greatly
      increased the percentage of patients in whom venous thrombosis can be attributed
      to hereditary thrombophilia. The first step in the diagnostic approach to all
      patients with venous thrombosis consists of a careful history and physical
      examination combined with routine laboratory testing to characterize the severity
      of the thrombotic condition and determine the presence of any of the acquired
      causes of hypercoagulability. The second step is to consider screening for the
      causes of hereditary and acquired thrombophilia in selected subsets of patients.
      The selection of patients for testing, the choice of tests to perform, and the
      timing of the testing are important and challenging issues to consider. Routine
      testing would be warranted if the identification of abnormalities led to an
      alteration in the type or duration of initial anticoagulant therapy or the use of
      long-term prophylactic anticoagulation. The available data, however, do not yet
      indicate that most patients with defined thrombophilic states should be managed
      any differently than patients without identifiable abnormalities. On the basis of
      relative prevalences of the various thrombophilias, patients can be classified as
      "strongly" or "weakly" thrombophilic depending on their thrombotic histories.
      Management considerations and guidelines are offered for patients who are found
      to have one or more defined abnormalities, hereditary or otherwise. The future
      identification of additional laboratory abnormalities predisposing patients to
      thrombosis, coupled with prospective clinical trials, should enable us to better
      identify patients at high risk for recurrence who will benefit from prolonged
      anticoagulant prophylaxis.

PMID- 11529701
TI  - Restricted activity: key indicator of decline or "just having a bad day"?.

PMID- 11529703
TI  - Deep waters run still.

PMID- 11529704
TI  - Methylene blue improves the hepatopulmonary syndrome.

PMID- 11529706
TI  - Periodic liver biopsy for mild hepatitis C.

PMID- 11529708
TI  - Cost-effectiveness analyses.

PMID- 11529710
TI  - Ultrasonography in management of nodular thyroid disease.

PMID- 11529711
TI  - Ultrasonography in management of nodular thyroid disease.

PMID- 11529713
TI  - Doxepin-induced torsade de pointes tachycardia.

PMID- 11529714
TI  - To change or not to change: "Sounds like you have a dilemma".

PMID- 11529717
TI  - 100 years of carbocations and their significance in chemistry.

PMID- 11529718
TI  - Solid-phase synthesis of the alkenyldiarylmethane (ADAM) series of non-nucleoside
      HIV-1 reverse transcriptase inhibitors.
AB  - The Sonogashira and Stille cross-coupling reactions have been employed in the
      synthesis of several non-nucleoside reverse transcriptase inhibitors (NNRTIs) in
      the alkenyldiarylmethane (ADAM) series. The synthesis has been carried out both
      in solution and on a solid support. In contrast to previous syntheses of NNRTIs
      in the ADAM series, the present strategy allows the incorporation of differently
      substituted aromatic rings in a stereochemically defined fashion. The most potent
      of the new ADAMs inhibited the cytopathic effect of HIV-1RF in CEM-SS cell
      culture with an EC50 value of 20 nM.

PMID- 11529719
TI  - Highly diastereoselective 1,4-addition of an organocuprate to methyl alpha-D
      gluco-, alpha-D-manno-, or alpha-D-galactopyranosides tethering an alpha,beta
      unsaturated ester. Novel asymmetric access to beta-C-substituted butanoic acids.
AB  - The 1,4-addition of magnesium divinylcuprate prepared from vinylmagnesium bromide
      and cuprous bromide to some 4-O-crotonyl derivatives of methyl alpha-D
      glucopyranoside proceeds with a high level of diastereochemical induction,
      providing the adduct in good-to-excellent yields. Other organocuprates also serve
      as effective carbon nucleophiles for the 1,4-addition. Removal of the
      carbohydrate moiety from each adduct afforded a variety of beta-C-substituted
      butanoic esters in remarkable enantiomeric excess. The 1,4-addition of the same
      cuprate to some methyl alpha-D-manno- or alpha-D-galactopyranosidic substrates in
      which a crotonyl group was incorporated, each at 3-OH, was also investigated. The
      reverse pi-facial attack of the cuprate was observed when some D-manno-type
      substrates were subjected to 1,4-addition conditions similar to those used for
      the D-gluco-type substrates. Furthermore, some D-galacto-type substrates provided
      1,4-adducts with higher diastereoselectivities.

PMID- 11529720
TI  - Synthesis of a tetrahomodioxacalix[4]arene tetraamide and the crystal structure
      of its lead ion complex.
AB  - The 1,4-alternate tetrahomodioxacalix[4]arene tetraamide 4 with four p-phenyl
      groups on its upper rim was synthesized. In two-phase metal picrate extraction, 4
      exhibited Pb2+ selectivity with formation of a 1:1 complex in chloroform. In the
      solid-state structure of the 4*Pb(Pic)2 complex, Pb2+ is bound by the carbonyl
      oxygens of two adjacent amide groups and an aryl-alkyl ether oxygen atom of one
      of these amide-containing substituents. The crystal structure and 1H NMR spectrum
      of the 4*Pb2+ complex reveals pi-metal ion complexation of one aromatic ring in
      the ligand with Pb2+.

PMID- 11529721
TI  - A computational study of the reactions of thiiranes with ammonia and amines.
AB  - The relative rates of reaction of thiirane and thiirane derivatives with NH3, a
      series of secondary amines including aziridine, and trimethylamine were
      determined in the gas phase by means of B3LYP/6-31+G(d)//HF/6-31+G(d)
      computations and transition state theory. Convergence of the results was
      selectively tested using the 6-311++G(d,p) basis set. Comparison with MP2/6-31 +
      G(d)//MP2/6-31G(d) computations was made in model cases. These results are
      significant in that they supplement the only reported gas-phase experimental
      study of this type of reaction. The reaction rates of thiirane with secondary
      amines can best be rationalized by means of an interplay of steric and
      polarizability effects. While beta-halo substituents retard S(N)2 reactions in
      solution, both 2-fluorothiirane and its acyclic model react more than l0(6) times
      faster with NH3 than the unsubstituted compounds in the gas phase. 2
      Fluorothiirane was calculated to react with NH3 at C2 by a factor of 0.142 with
      respect to thiirane itself; attack at C3 was found to be 3.42 x 10(6) times
      faster than the parent compound. 2-Methylthirane reacts with NH3 at 0. 230 the
      rate of thiirane with a 12.8-fold regioselectivity for C3. In the reaction of 2,2
      dimethylthirane and NH3, this preference for C3 increases to a factor of 124.
      Ground-state destabilization of cis-2,3-dimethylthiirane is sufficient to account
      for its calculated rate acceleration with respect to the trans isomer.

PMID- 11529722
TI  - Crystal engineering using anilic acids and dipyridyl compounds through a new
      supramolecular synthon.
AB  - The anilic acids, 2,5-dihydroxy-1,4-benzoquinone (1a), 2,5-dibromo-3,6-dihydroxy
      1,4-benzoquinone (bromanilic acid; 1b), 2,5-dichloro-3,6-dihydroxy-1,4
      benzoquinone (chloranilic acid; 1c), and 2,5-dicyano-3,6-dihydroxy-1,4
      benzoquinone (cyananilic acid; 1d), were cocrystallized with rigid organic
      ligands containing two pyridine rings, 2,4-bipyridine (2a), 4,4'-bipyridine (2b),
      1,2-bis(2-pyridyl)ethylene (3a), 1,2-bis(4-pyridyl)ethylene (3b), 2,2'
      dipyridylacetylene (4a), 3,3'-dipyridylacetylene (4b), and 4,4'
      dipyridylacetylene (4c). Fourteen complexes 5-18 were obtained as single
      crystals, and their crystal structures were successfully determined by X-ray
      analysis. All complexes except those with 2a are 1:1 and are composed of an
      infinite linear or zigzag tape structure, the formation of which is ascribed to
      intermolecular O-H...N, N(+)-H...O, or N(+)-H...O(-) hydrogen bonds or a
      combination of these between the anilic acids and the dipyridyl compounds. In the
      complexes 5 and 6, no infinite tape structure is observed although the molecular
      units connected by a similar hydrogen-bonding pattern are formed. For the 1:1
      complexes, we have found two types of stacking arrangements, segregated stacks
      (7, 9, 12-15, 18) and alternated ones (8, 10, 11, 16, 17). In the complexes of 1c
      with the series of dipyridylacetylenes 4 (14, 15, 17), the neutral, dication, and
      monocaction states are formed depending on the nitrogen positions, which can be
      attributed to the different basicity of the pyridyl groups.

PMID- 11529723
TI  - Phenyl-bridging in the 2-phenylethyl radical. A molecular orbital study.
AB  - Density functional theory at the UB3PW91/6-31G(d.p) level on the open and bridged
      forms of the 2-phenylethyl radical are reported here together with activation
      energies and calculated rate constants for rearrangement of the bridged to the
      open radical. In addition, the effect of substituents on the aryl ring upon the
      relative energies, activation energies, and rate constants for rearrangement from
      the bridged to open forms are presented. Para-substituents include CH3, CF3.CN,
      CHO.OH, SH, O-, S-, and NO. The parent bridged radical is found to be 10.1
      kcal/mol higher in enthalpy than the open form. The activation energy for
      conversion of the bridged to open radical is 3.96 kcal/mol. Para-substitution by
      CN or CHO significantly lowers the difference in energy between the species,
      while substitution by NO renders the bridged form more stable. Para-substitution
      by CN or CHO coupled with substitution with CN in the ortho-positions makes the
      open and bridged radical approximately equivalent in energy.

PMID- 11529724
TI  - Concerted mechanisms of the reactions of 2,4,6-trinitrophenyl methyl carbonate
      and 2,4,6-trinitrophenyl acetate with secondary alicyclic amines.
AB  - The reactions of secondary alicyclic amines with 2,4,6-trinitrophenyl methyl
      carbonate (TNPMC) and 2,4,6-trinitrophenyl acetate (TNPA) are subjected to a
      kinetic study in aqueous solution, 25.0 degrees C, ionic strength 0.2 (KCl). The
      reactions are studied by following spectrophotometrically (360 nm) the release of
      the 2,4,6-trinitrophenoxide anion. Under amine excess, pseudo-first-order rate
      coefficients (k(obsd)) are found. Plots of k(obsd) vs [amine] are linear, with
      the slope (kN) independent of pH. The Bronsted-type plots (log k(N) vs pK(a) of
      the conjugate acid of the amines) are linear, with slopes beta = 0.41 and beta =
      0.36 for the reactions of TNPA and TNPMC, respectively. The predicted breaks of
      the Bronsted plots for stepwise mechanisms are pK(a)0 = 6.8 and 7.3,
      respectively. The lack of Bronsted breaks for these reactions and the values of
      the Bronsted slopes are consistent with concerted mechanisms. By comparison of
      the reactions under investigation among them and with similar aminolysis and
      pyridinolysis, the following conclusions can be drawn: (i) Secondary alicyclic
      amines react with TNPA and TNPMC by concerted mechanisms. (ii) TNPA is more
      reactive toward these amines than TNPMC due to the greater electron release of
      MeO from the latter substrate. (iii) The change of 2,4-dinitrophenoxy to 2,4,6
      trinitrophenoxy in the zwitterionic tetrahedral intermediate (T+/-) formed in the
      reactions of the title amines with 2,4-dinitrophenyl acetate greatly destabilizes
      T+/-. (iv) Secondary alicyclic amines destabilize T+/- relative to pyridines. (v)
      The intermediate T+/- formed in the reactions of the title amines with S-(2,4,6
      trinitrophenyl) acetate is greatly destabilized by substitution of S-(2,4,6
      trinitrophenyl) by O-(2,4,6-trinitrophenyl) as the leaving group.

PMID- 11529725
TI  - Lithium reduction of the bowl-shaped C60 fragment diindeno[1,2,3,4
      defg;1',2',3',4'-mnop]chrysene: an interplay between experiment and calculation.
AB  - Diindeno[1,2,3,4-defg;1',2',3',4'-mnop]chrysene (DIC) (one of the smallest
      symmetrical bowl-shaped fragments of C60) and its tetra-tert-butyl derivative are
      reduced with lithium metal to yield dianions and tetraanions. Due to the high
      degree of symmetry (C2v) of DIC and its derivative, their NMR spectra cannot be
      assigned using the standard two-dimensional NMR techniques. A novel carbon-edited
      NOESY method was used to complete the assignments of the neutral and dianion
      species, whereas the tetraanions are aided by DFT calculations for their
      assignment. Experimental charge-distribution patterns were obtained and match
      those of the calculations. An extension of the empirical approach for estimating
      the charge distribution from the 13C NMR spectra enables a direct comparison
      between experimentally derived charge-distribution data and the computed electron
      density in each of the lowest unoccupied molecular orbitals. The overall picture
      evolving from the orbital structure of DIC is presented and reflects the surface
      reactivity of C60.

PMID- 11529726
TI  - Palladium-catalyzed tandem dimerization and cyclization of acetylenic ketones: a
      convenient method for 3,3'-bifurans using PdCl2(PPh3)2.
AB  - Alkynones undergo tandem dimerization and cyclization in the presence of
      PdCl2(PPh3)2 and triethylamine in tetrahydrofuran at room temperature to give
      3,3'-bifurans predominantly. Other palladium catalysts while under similar
      conditions, by rearrangement, lead to 2,5-disubstituted furans. This
      distinguished property of PdCl2(PPh3)2 has been attributed to the involvement of
      hydridopalladium halide. This method provides a simpler route to a variety of
      furans and a regioselective synthesis of polysubstituted 3,3'-bifurans using
      easily accessible acetylenic ketones.

PMID- 11529727
TI  - Novel synthesis of alkenes via triethylborane-induced free-radical reactions of
      alkyl iodides and beta-nitrostyrenes.
AB  - Reactions of (E)-beta-nitrostyrenes 1 and triethylborane 2 or tricyclohexylborane
      4 in THF solution at room temperature in the presence of oxygen in the air as
      radical initiator generate high yields of trans-alkenes (E)-3 or (E)-5. Medium to
      high yields of different (E)-alkenes (E)-5, 7, 10, 12, and 14 also can be
      prepared when 1 reacts with different radicals, prepared from secondary alkyl
      iodides 6 and 8 or tertiary alkyl iodides 9, 11, and 13, in the presence of 2 and
      air as radical initiator. The generation of the only product (E)-alkenes can be
      explained by the generation of the benzylic radical A and/or B as the
      intermediate only and the mechanism is similar to Scheme 1. Both (E)- and (Z)-16a
      c are generated when (E)- and (Z)-15a-c are used to react with adamantyl radical
      under similar conditions. Only (Z)-16d was observed when either (E)- or (Z)-15d
      was used to react with adamantyl radical. The generation of the (E)- and/or (Z)
      alkenes can be explained by the free rotation of the A and/or B to generate A'
      and/or B' and vice versa, and the mechanism is proposed to be a free-radical
      reaction via NO2/alkyl substitution and is shown as Scheme 2.

PMID- 11529728
TI  - Aromatic dienophiles. 1. A theoretical study of an inverse-electron demand Diels
      Alder reaction between 2-aminopyrrole and 1,3,5-triazine.
AB  - This study is devoted to a detailed theoretical study of an inverse-electron
      demand Diels-Alder reaction (IDA) with 1,3,5-triazine as the diene and 2
      aminopyrrole 1A(alpha) as the dienophile, which is a key step in a cascade
      reaction for the one-pot synthesis of purine analogues. Geometries were optimized
      with the B3LYP/6-31G* method and energies were evaluated with the MP2/6-311++G**
      method. This IDA reaction occurs through a stepwise mechanism, where the first
      step corresponds to the nucleophilic attack of 2-aminopyrrole to triazine to form
      a zwitterionic intermediate, which is in equilibrium with a neutral intermediate
      through a hydrogen transfer process, followed by a rate-determining ring-closure
      step. It is shown that the B3LYP method significantly overestimates the
      activation energy, whereas the MP2 method offers a reasonable activation barrier
      of 27.9 kcal/mol in the gas phase. The solvation effect has been studied by the
      PCM model. In DMSO, the calculated activation energy of the IDA reaction is
      decreased to 24.0 kcal/mol with a strong endothermicity of 17.4 kcal/mol due to
      the energy penalty of transforming two aromatic reactants into a nonaromatic IDA
      adduct. The possible stepwise [2+2] pathway is ruled out based on its higher
      activation and reaction energies than those of the [4+2] pathway. By comparing
      the IDA reactions of triazine to 2-aminopyrrole and pyrrole, we address two
      crucial roles of the alpha-amino substituent in lowering activation and reaction
      energies and controlling the reaction regiochemistry.

PMID- 11529729
TI  - Studies on the total synthesis of disorazole C1. An advanced macrocycle
      intermediate.
AB  - Synthesis of protected tetradehydro-(6,6'-S)-(14,14'-S)-(16,16'-R)-disorazole
      (3), a potential precursor to the natural product disorazole C1 (1), is
      described. Key features of this work include (a) an unprecedented sequential 1,5
      O --> O silyl rearrangement/Horner-Wadsworth-Emmons reaction used to construct
      18, (b) a highly convergent Sonogashira reaction between the dienyl iodide 7 and
      the alkyne 8 to assemble the dienyne monomeric fragment 5, and (c) the selective
      cyclization of 5 to give either the cyclic monomer 23 or the dimer 3.

PMID- 11529731
TI  - Regio- and diastereoselective synthesis of 2-alkylidenetetrahydrofurans by domino
      SN/SN' and SN/SN reactions of 1,3-dicarbonyl dianions.
AB  - The domino C,O-cyclodialkylation reaction of dilithiated 1,3-dicarbonyl compounds
      with 1,4-dibromo-2-butene resulted in regio- and diastereoselective formation of
      2-alkylidene-5-vinyltetrahydrofurans. The cyclization of 1,3-dicarbonyl dianions
      with 1-bromo-2-chloroethane regio- and diastereoselectively afforded 2
      alkylidenetetrahydrofurans under thermodynamic reaction control.

PMID- 11529730
TI  - Conformational study and enantioselective, regiospecific syntheses of novel
      aminoxy trans-proline analogues derived from an acylnitroso Diels-Alder
      cycloaddition.
AB  - The cis/trans isomerization of the proline amide bond has many implications in
      biological processes. The conformations of representative acylnitroso-derived
      proline analogues derived from cyclopentadiene were shown to exist exclusively as
      the E or trans conformation in CD2Cl2. The energetically favored conformations
      were determined using COSMO self-consistent reaction field calculations at the
      B3LYP/6-31G level of theory in addition to low temperature 1H NMR studies. The
      syntheses of the acylnitroso-derived peptides utilized two methods to selectively
      functionalize either of two chemically similar esters in the acylnitroso-derived
      amino acids. A novel transpeptidation of the amino acid that controlled the
      absolute stereochemistry in the acylnitroso Diels-Alder cycloaddition took
      advantage of an activated aminoxy amide linkage to control regiochemistry.
      Alternatively, an enantioselective and regiospecific enzymatic resolution of a
      racemic dimethyl ester provided a novel aminoxy acid.

PMID- 11529732
TI  - Fluorophore-labeled S-nitrosothiols.
AB  - A series of fluorophore-labeled S-nitrosothiols were synthesized, and their
      fluorescence enhancements upon removal of the nitroso (NO) group were evaluated
      either by transnitrosation or by photolysis. It was shown that, with a suitable
      alkyl linker, the fluorescence intensity of dansyl-labeled S-nitrosothiols could
      be enhanced up to 30-fold. The observed fluorescence enhancement was attributed
      to the intramolecular energy transfer from fluorophore to the SNO moiety. Ab
      initio density functional theory (DFT) calculations indicated that the "overlap"
      between the SNO moiety and the dansyl ring is favored because of their
      stabilizing interaction, which was in turn affected by both the length of the
      alkyl linker and the rigidity of the sulfonamide unit. In addition, one of the
      dansyl-labeled S-nitrosothiols was used to explore the kinetics of S
      nitrosothiol/thiol transnitrosation and was evaluated as a fluorescence probe of
      S-nitrosothiol-bound NO transfer in human umbilical vein endothelial cells.

PMID- 11529733
TI  - Cyclizations of 4-pentenyl, 5-hexenyl, 6-heptenyl, and 7-octenyl fluorinated
      radicals: a density functional theory theoretical study.
AB  - The cyclization reactions of the 4-pentenyl, 5-hexenyl, 6-heptenyl, and 7-octenyl
      fluorinated and ether radicals have been studied by a hybrid Hartree-Fock density
      functional method. The reliability of this approach has been confirmed in
      agreement with experimental data and post-Hartree-Fock projected Moller-Plesset
      second-order method. The analysis of the theoretical results shows that two
      factors are crucial for the determination of the regiochemistry and the
      reactivity of these reactions. The first factor is the ability of the starting
      radical to have a stable conformation in position to form the transition state,
      and the second one is the enthalpic effect of the reaction through the stability
      of the resulting cyclized radical. It should be pointed out that these factors
      are not linked to the polarity of the radicals due to the presence of CF2 groups.

PMID- 11529734
TI  - Synthesis of biaryls by intramolecular radical transfer in phosphinates.
AB  - Phosphinates 20a-35a give biaryls 20b-35b on heating with stannanes in the
      presence of AIBN. The process involves a radical ipso substitution on the
      migrating aryl ring.

PMID- 11529735
TI  - Barriers to rotation in methyl formate by dynamic NMR spectroscopy and barriers
      to 1,3 oxygen-to-oxygen migration in methyl formate and trifluoromethyl formate
      by ab initio calculations.
AB  - Free-energy barriers of 9.85 and 11.91 +/- 0.15 kcal/mol at -70.8 degrees C were
      found by dynamic NMR spectroscopy for the E-to-Z and Z-to-E conversions,
      respectively, of methyl formate (1) enriched in 13C to 99% for the carbonyl
      carbon [methyl formate 13C (2)]. These barriers are higher than the literature
      values reported for -53 degrees C. The free-energy barrier to 1,3 oxygen-to
      oxygen migration of the methyl group in methyl formate was determined by ab
      initio calculations at several levels. The value of 58.7 kcal/mol obtained at the
      MP2/6-311+G (df,pd) level was compared to a literature barrier for this process
      (MINDO/3) and to barriers for related compounds. A free-energy barrier of 63.0
      kcal/mol for the oxygen - to - oxygen migration of the CF3 group in
      trifluoromethyl formate (3) was calculated at the MP2/6-31+G level.

PMID- 11529736
TI  - Nitrous oxide as a 1,3-dipole: a theoretical study of its cycloaddition
      mechanism.
AB  - The 1,3-dipolar cycloadditions of nitrous oxide and substituted alkynes have been
      studied at the B3LYP/6-31G(d,p) level. The reaction is controlled by LUMO
      (dipole)--HOMO (dipolarofile) and involves aromatic transition structures. The
      shape of the potential energy surface and the regioselectivity are not affected
      by the polarity of the solvents, except in the case of N2O + HC triple bond
      CSiH3. Different reactivity criteria including FMO coefficients product C, local
      softness differences Delta, magnetic susceptibility anisotropy chi(anis), and
      nucleus-independent chemical shifts NICS were used to predict the
      regioselectivity in all studied cases; the C, Delta criteria turn out to give the
      best results among them. The aromaticity of the transition structure is not a
      factor in determining the regiochemistry of the cycloaddtition reactions.

PMID- 11529737
TI  - Ester-armed cyclens having quadruplicated helical geometry: remarkably stable and
      selective encapsulation of Na+ ion.
AB  - A new series of ester-armed cyclens nicely accommodated a Na+ ion in their
      quadruplicated helical binding spheres and effectively discriminated the cation
      from Li+ and K+ ions. Crystallographic studies revealed that four ester
      functionalized sidearms provided effective coordination with the Na+ ion trapped
      in the 12-membered cyclen ring. Log K values for their Na+ complexes were
      estimated as 9-11 in CD3CN or C2D5OD, which were comparable to those of common
      bicyclic cryptands. FAB-MS, liquid-liquid extraction, and NMR binding experiments
      demonstrated that the cooperative action of the parent cyclen ring and ester
      functionalized sidearms offered stable and selective encapsulation of the Na+ ion
      based on unique quadruplicated helical geometry.

PMID- 11529738
TI  - Elongation of the pi-system of phthalocyanines by introduction of thienyl
      substituents at the peripheral beta positions. Synthesis and characterization.
AB  - 1,4,8,11,15,18,22,25-octabutoxyphthalocyanines ((OBu)8Pcs) having eight 2-thienyl
      (1) and [2,2'-bithiophene]-5-yl (2) groups at beta positions and their zinc(II)
      and cobalt(II) derivatives were prepared from 2-thienyl- (3) or [2,2'
      bithiophene]-5-yl (4)-substituted phthalonitriles in moderate to good yields. The
      electronic absorption spectra of the Pcs showed red-shifted Q-bands relative to
      beta-unsubstituted (OBu)8Pcs. The longer substituent, the [2,2'-bithiophene]-5-yl
      group, is more effective than the 2-thienyl group in enlarging the pi-conjugated
      system of the Pcs. The ring oxidation potential obtained by cyclic voltammetry
      shifted cathodically with increasing chain length, indicating destabilization of
      the HOMOs. Due to the shift of the Q-band, 2-thienyl- and [2,2'-bithiophene]-5-yl
      substituted Pcs exhibit a remarkable color change from the original green color.

PMID- 11529739
TI  - Stereospecific 1,3-migration of an Fe(CO)3 group on acyclic conjugated polyenes:
      application to remote and iterative asymmetric induction.
AB  - The stereochemical outcome of the 1,3- and 1,5-migration of an Fe(CO)3 group on
      (acyclic polyene)Fe(CO)3 complexes and their application to stereoselective
      construction of remote and contiguous stereogenic centers are described.
      Treatment of the [(eta(4)-4-7)triene]Fe(CO)3 complexes 1a-d bearing an electron
      withdrawing group on the terminal position of an uncomplexed olefin with a base
      such as KN(SiMe3)2 (KHMDS) and LiCH2CN induced the 1,3-migration reaction of the
      Fe(CO)3 group, giving the [(eta4-2-5)triene]Fe(CO)3 complexes 2a-d in moderate to
      good yields, depending on the electron-withdrawing groups. From an experiment
      using the chiral (trienenitril)Fe(CO)3 complex 5, it is revealed that the 1,3
      migration proceeds with inversion of configuration. Similarly, the 1,5-migration
      reaction of the[(eta4-6-9)tetraenone]Fe(CO)3 complexes 9 occurred with a
      catalytic amount of KHMDS, giving the [(eta4-2-5)tetraenone]Fe(CO)3 complexes 10
      with retention of configuration. Furthermore, we have succeeded in the first
      regio- and stereoselective nucleophilic substitution of the (3,5-diene-1,2-diol)
      Fe(CO)3 complexes (15 --> 24a-h) with various nucleophiles via the ortho esters
      21. By using iterative manipulation of the above two reactions, remote
      stereocontrol of the terminal substituents on acyclic polyene (9 --> 12) and
      construction of contiguous stereogenic centers (19, 28) have been achieved.

PMID- 11529740
TI  - On the synthesis and reactivity of the Z-2,4-dinitrophenylhydrazone of 5-amino-3
      benzoyl-1,2,4-oxadiazole.
AB  - The synthesis of the title compound (4b) has been completed: its rearrangement
      (in dioxane/water; 1:1, v/v) into N-(2,4-dinitrophenyl)-5-phenyl-2H-1,2,3-triazol
      4-ylurea (7) has been quantitatively studied in a wide reactivity (at 293 K, k(A)
      10(-8) -4 s(-1)) and pS+ (4.5-14.1) range and compared with that of the Z-2,4
      dinitrophenylhydrazone of 3-benzoyl-5-phenyl-1,2,4-oxadiazole (10), of the 3-(p
      nitro)phenylureine of 5-phenyl-1,2,4-oxadiazole (13), and of N-(5-phenyl-1,2,4
      oxadiazol-3-yl)-N'-p-nitrophenylformamidine (14). The results (reactivity,
      occurrence of specific or general base-catalysis, evidence for or absence of rate
      limiting constants) have been well interpreted considering the structure of the
      side-chains involved and the stability of the final rings obtained in the
      rearrangements.

PMID- 11529741
TI  - Kinetics and mechanisms of the reactions of 3-methoxyphenyl, 3-chlorophenyl, and
      4-cyanophenyl 4-nitrophenyl thionocarbonates with alicyclic amines.
AB  - The reactions of 3-methoxyphenyl, 3-chlorophenyl, and 4-cyanophenyl 4-nitrophenyl
      thionocarbonates (1, 2, and 3, respectively) with a series of secondary alicyclic
      amines are studied kinetically in 44 wt % ethanol-water at 25.0 degrees C and an
      ionic strength of 0.2 M (KCl). Pseudo-first-order rate coefficients (k(obsd)) are
      obtained for all reactions (amine excess was used). The reactions of compound 1
      with piperidine, piperazine, and 1-(2-hydroxyethyl)piperazine and of compounds 2
      and 3 with these amines and morpholine exhibit linear k(obsd) versus amine
      concentration plots with slopes (k1) independent of pH. In contrast, the plots
      are nonlinear upward for the reactions of substrate 1 with morpholine, 1
      formylpiperazine, and piperazinium ion and of substrates 2 and 3 with the two
      latter amines. For all these reactions, a reaction scheme is proposed with a
      zwitterionic tetrahedral intermediate (T+/-), which can be deprotonated by an
      amine to yield an anionic intermediate (T-). When the nonlinear plots are fit
      through an equation derived from the scheme, rate and equilibrium
      microcoefficients are obtained. The Bronsted-type plots for k1 are linear with
      slopes of beta1 = 0.22, 0.20, and 0.24 for the aminolysis of 1, 2, and 3,
      respectively, indicating that the formation of T+/- (k1 step) is rate
      determining. The k1 values for these reactions follow the sequence 3 > 2 > 1,
      which can be explained by the sequence of the electron-withdrawing effects from
      the substituents on the nonleaving group of the substrates.

PMID- 11529743
TI  - Efficient synthesis of 1alpha-fluoro A-ring phosphine oxide, a useful building
      block for vitamin D analogues, from (S)-carvone via a highly selective palladium
      catalyzed isomerization of dieneoxide to dieneol.
AB  - The 1alpha-fluoro A-ring phosphine oxide 1, a useful building block for
      fluorinated vitamin D analogues, was synthesized from (S)-carvone in 13 synthetic
      steps, and only five isolations, in 22% overall yield. In the key synthetic step,
      a highly selective palladium-catalyzed isomerization of dieneoxide 18 to dieneol
      20 was achieved using an appropriately selected fluorinated alcohol as a
      catalytic proton source.

PMID- 11529742
TI  - Optically active BINOL core-based phenyleneethynylene dendrimers for the
      enantioselective fluorescent recognition of amino alcohols.
AB  - A dramatic enhancement in fluorescence intensity from 1,1'-bi-2-naphthol (BINOL)
      to dendritic phenyleneethynylenes containing the BINOL core was observed. The
      strong fluorescence of the dendrimers allows a very small amount of the chiral
      materials to be used for sensing. The light harvesting antennas of the dendrimer
      funnel energy to the center BINOL unit, whose hydroxyl groups upon interaction
      with a quencher molecule lead to fluorescence quenching. This mechanism makes the
      dendrimers have much more sensitive fluorescence responses than corresponding
      small molecule sensors. The fluorescence of these dendrimers can be
      enantioselectively quenched by chiral amino alcohols. It is observed that the
      fluorescence lifetime of the generation two dendrimer does not change in the
      presence of various concentrations of 2-amino-3-phenyl-1-propanol. This
      demonstrates that the fluorescence quenching is entirely due to static quenching.
      Thus, formation of nonfluorescent ground-state hydrogen-bond complexes between
      the dendrimers and amino alcohols is proposed to account for the fluorescent
      quenching. A linear relationship has been established between the Stern-Volmer
      constant of the generation two dendrimer and the enantiomeric composition of 2
      amino-3-phenyl-1-propanol. Such enantioselective fluorescent sensors may allow a
      rapid determination of the enantiomeric composition of chiral molecules and are
      potentially useful in the combinatorial search of asymmetric catalysts and
      reagents.

PMID- 11529744
TI  - A theoretical study of the reaction between cyclopentadiene and protonated imine
      derivatives: a shift from a concerted to a stepwise molecular mechanism.
AB  - The reaction between cyclopentadiene and protonated pyridine-2-carboxaldehyde
      imine derivatives has been studied by using Hartree-Fock (HF) and B3LYP methods
      together with the 6-31G basis set. The molecular mechanism is stepwise along an
      inverted energy profile. This results from the protonation on both nitrogen atoms
      of the imine group and the pyridine framework. The first step corresponds to the
      nucleophilic attack of cyclopentadiene on the electron-poor carbon atom of the
      iminium cation group to give an acyclic cation intermediate, and the second step
      is associated with the ring closure of this intermediate via the formation of a C
      N single bond yielding the final cycloadduct. Two reactive channels have been
      characterized corresponding to the endo and exo approach modes of the
      cyclopentadiene to the iminium cation. The role of the pyridium cation
      substituent and the nitrogen position (ortho, meta, and para) along the reaction
      pathway has been also considered. Solvent effects (dichloromethane) by means of a
      continuum model have been taken into account to model the experimental
      environment.

PMID- 11529745
TI  - Structure-activity studies of antitumor agent irofulven
      (hydroxymethylacylfulvene) and analogues.
AB  - Many analogues of the antitumor agent irofulven have been readily prepared by
      replacing the allylic hydroxyl with a variety of nucleophiles. Analogues of
      acylfulvene (the precursor to irofulven) were also prepared by Michael reaction
      with acrolein. The toxicity of the analogues was determined, as well as
      preclinical antitumor activity. Several analogues exhibited good activity in
      mouse xenografts. Structural requirements for activity are discussed.

PMID- 11529746
TI  - Crystal structure-reactivity correlation in single-crystalline photochromism of
      1,2-bis(2-methyl-5-phenyl-3-thienyl)perfluorocyclopentene.
AB  - Single-crystalline photochromism of 1,2-bis(2-methyl-5-phenyl-3
      thienyl)perfluorocyclopentene 1a was followed in situ by X-ray crystallographic
      analysis. The crystal of 1a has two molecules with different conformations in the
      crystallographic asymmetric unit. The X-ray analysis of the photoirradiated
      crystal showed that the photocyclization reaction of the molecule with the
      shorter distance between the reactive carbons prevails over the reaction of the
      other molecule. The mechanism has been discussed based on the calculation of the
      electronic transitions of the two molecules in the different conformations. The
      photocyclization quantum yield was determined to be 1 (100%) in the crystal.

PMID- 11529747
TI  - A new versatile receptor platform.
AB  - We prepared a molecular receptor based on the molecular tweezer concept. Our
      system offers versatility, an extremely short synthetic route, good yield, large
      quantities, and finally having binding constants that equal the best known
      tweezer molecules when it comes to binding various nitroaromatics such as 1,3,5
      trinitrotoluene (24 M(-1)), 1,3,5-trinitrobenzene (182 M(-1)), and 2,4,7
      trinitrofluorenone (490 M(-1)) as determined using 1H NMR in CDCl3. It is notable
      that these binding constants are achieved although the molecular framework is not
      locked in a fixed and rigid conformation. The rigidity has been claimed to be the
      governing factor when it comes to achieving a large binding constant. We propose
      that our molecular tweezer system may be preorganized and that this explains the
      high binding constants observed. Further, we investigated the crystal structures
      of both the neutral receptor molecule and a complex with 1,3,5-trinitrobenzene
      and found that the molecule forms a pocket suited to accommodate flat aromatic
      analytes.

PMID- 11529748
TI  - Synthetic use of poly[4-hydroxy(tosyloxy)iodo]styrenes.

PMID- 11529749
TI  - Direct evaluation of secondary orbital interactions in the Diels-Alder reaction
      between cyclopentadiene and maleic anhydride.

PMID- 11529751
TI  - Electrogenerated base-induced N-acylation of chiral oxazolidin-2-ones.

PMID- 11529750
TI  - Effects of structure on the free radical reactions of hydridophosphoranes with
      dimethyl sulfide.

PMID- 11529752
TI  - Dictyonamides A and B, new peptides from marine-derived fungus.

PMID- 11529753
TI  - Synthesis of indolizidine and quinolizidine derivatives via intramolecular
      cyclization of alkynyltungsten compounds with N-acyliminium ion.

PMID- 11529754
TI  - A switch of reactivity profile in ionic intramolecular annulation reactions: a
      short and efficient synthesis of D-+-biotin.

PMID- 11529755
TI  - Evidence for the biosynthesis of squalene via the methylerythritol phosphate
      pathway in a Streptomyces sp. obtained from a marine sediment.

PMID- 11529756
TI  - A new and direct synthesis of 2-substituted pyrrolidines.

PMID- 11529757
TI  - Reductive activation of mitomycin A by thiols.
AB  - [reaction: see text]. Mitomycin C is unchanged upon exposure to thiols under
      physiological conditions. Its more toxic variant, mitomycin A (MA), undergoes
      elimination of methanol to give a variety of mitosene derivatives, diagnostic of
      its activation to a reactive electrophile. Evidence is presented for a novel
      reductive mechanism, characterized by the transient addition of a thiol to the
      quinone of MA, followed by intramolecular electron transfer, leading to reduced
      quinone and oxidized thiol.

PMID- 11529758
TI  - The 5,6- and 4,5-benzo derivatives of 1-hydroxy-7-azabenzotriazole.
AB  - [structure: see text]. Syntheses of the two benzo derivatives of HOAt are
      described. Conversion of the two isomers to the corresponding onium-style
      coupling reagents gave in one case a guandinium species 14 and in the other,
      presumably as a result of steric factors, a uronium species 15. The two systems
      are compared as to their effectiveness in peptide coupling processes.

PMID- 11529759
TI  - Solid-phase synthesis of 1,7-disubstituted-1,3,5-triazepane-2,4-diones.
AB  - [reaction: see text]. The solid-phase synthesis of 1,7-disubstituted-1,3,5
      triazepane-2,4-diones from resin-bound amino acids is described. The exhaustive
      reduction of solid-support bound amides with borane afforded the requisite
      secondary amines, which following treatment with phenyl isocyanatoformate and
      cleavage, provided the corresponding triazepane-2,4-diones.

PMID- 11529760
TI  - The pH-dependent role of superoxide in riboflavin-catalyzed photooxidation of 8
      oxo-7,8-dihydroguanosine.
AB  - [reaction: see text]. The riboflavin-catalyzed photooxidation of 2',3',5'-tri-O
      acetyl-8-oxo-7,8-dihydroguanosine generates a radical intermediate that is
      competitively trapped by H(2)O, O2(-)(*), or O(2). The products of H(2)O trapping
      have been previously described as the spiroiminodihydantoin (pH >or= 7) and
      iminoallantoin/guanidinohydantoin (pH < 7) nucleosides. Trapping by O2(-)(*)
      leads to the oxaluric acid (pH <or= 7) and imidazolone (pH >or= 8.6) pathways (R'
      ', R' ' = H or 2,3,5-tri-O-Ac-ribofuranosyl). The pH-dependent role of superoxide
      was probed using Mn-SOD and compared to guanosine and 8-methoxyguanosine
      photooxidation.

PMID- 11529761
TI  - A novel one-pot conversion of aldehydes to trifluoromethylated bromoallylic
      alcohols.
AB  - [reaction: see text]. One-pot conversion of aldehydes to trifluoromethylated
      bromoallylic alcohols in the presence of titanium isopropoxide and
      triphenylphosphine is described.

PMID- 11529762
TI  - Regiospecific synthesis of 4-(2-oxoalkyl)pyridines.
AB  - [reaction: see text]. A new and operationally simple method has been developed
      for the regiospecific syntheses of 4-(2-oxoalkyl)pyridines from ketones and
      pyridine in good yields, using triflic anhydride to activate the pyridine ring.

PMID- 11529763
TI  - Studies on the total synthesis of tallysomycin. Synthesis of the
      threonylbithiazole moiety containing a structurally unique glycosylcarbinolamide.
AB  - [structure: see text]. Tallysomycins are glycopeptide antibiotics that were first
      isolated from fermentation broths of Streptoalloteichus hindustanus. They are
      structurally related to the bleomycins but contain an additional talose sugar
      attached via a unique glycosylcarbinolamide linkage. Herein we report the
      synthesis of a key tallysomycin intermediate that incorporates the
      glycosylcarbinolamide moiety unique to the tallysomycins.

PMID- 11529765
TI  - Intramolecular [2 + 2]-photocycloaddition/thermal fragmentation approach toward 5
      8-5 ring systems.
AB  - [reaction: see text]. An intramolecular [2 + 2]-photocycloaddition is used to
      provide a photoadduct, which upon fragmentation, lactone cleavage, and subsequent
      Cope rearrangement provides a dicyclopenta[a,d]cyclooctene ring system with
      substituents in place (e.g., C3 and C11) to access several 5-8-5 diterpene and
      sesterterpene natural products.

PMID- 11529764
TI  - Structure, histone deacetylase, and antiprotozoal activities of apicidins B and
      C, congeners of apicidin with proline and valine substitutions.
AB  - [structure: see text]. Isolation and structure elucidation of two novel cyclic
      tetrapeptides that show a variety of potent antiprotozoal activities by
      reversibly inhibiting HDAC have been reported. These are the new members of a
      unique family of cyclic tetrapeptides that do not require the electrophilic alpha
      epoxyketone moiety of HC-toxin, trapoxin A, or chlamydocin for their potent
      activities against HDAC and the malarial parasite.

PMID- 11529766
TI  - Synthesis of N-(3-arylpropyl)amino acid derivatives by Sonogashira types of
      reaction in aqueous media.
AB  - [reaction: see text]. N-propargylamino acids and peptides including them can be
      efficiently derivatized in aqueous media with a wide variety of (hetero)aryl
      halides by cross-coupling reactions catalyzed by palladium on carbon (10% Pd/C).

PMID- 11529767
TI  - A streamlined synthesis for 2,3-dihydroxyterephthalamides.
AB  - [reaction: see text]. 2,3-Dihydroxyterephthalamides have been synthesized through
      a route that avoids the protection and deprotection of the phenol groups. The
      procedure allows for symmetric and unsymmetric amide linkages. This synthetic
      sequence significantly decreases the time and cost of preparation and increases
      the overall yield of this class of metal chelators.

PMID- 11529769
TI  - Mild oxidative one-pot allyl group cleavage.
AB  - [reaction: see text]. A new one-pot method is described for the removal of O- and
      N-allyl protecting groups under oxidative conditions at near neutral pH. The
      allyl group undergoes hydroxylation and subsequent periodate scission of the
      vicinal diol, followed by repetition of this reaction sequence on the enolic form
      of the aldehyde intermediate.

PMID- 11529768
TI  - Regioselective aromatic borylation in an inert solvent.
AB  - [reaction: see text]. A protocol for performing Rh catalyzed aromatic borylations
      in cyclohexane has been devised. Borylation at the 5-position of several 1,3
      substituted aromatic species ranging from electron-rich (1,3-(NMe(2))(2)C(6)H(4))
      to electron-deficient (1,3-(CF(3))(2)C(6)H(4)) yields the corresponding aryl
      boronate esters. Veratrole was selectively borylated at the 4-position, thus
      extending regioselectivity to 1,2-substituted benzenes. Selective borylation at
      the 3-position of an N-protected pyrrole has also been demonstrated, providing a
      valuable reagent for cross-coupling reactions in a single step.

PMID- 11529770
TI  - Generation of (E)-silylketene acetals in a Rhodium-DuPhos catalyzed two-step
      reductive aldol reaction.
AB  - [reaction: see text]. Mechanistic studies employing in situ NMR analysis
      implicate intermediate silicon enolates as reactive intermediates in the Rh
      DuPhos catalyzed two-step reductive aldol reaction with Cl(2)MeSiH. These
      enolates undergo noncatalyzed reaction with a variety of aldehydes to give the
      derived syn-aldol adduct in high yields and diastereoselection.

PMID- 11529771
TI  - Synthesis of (+)-galiellalactone. Absolute configuration of galiellalactone.
AB  - [reaction: see text]. (+)-Galiellalactone was synthesized starting from (R)-(+)
      pulegone. Natural and synthetic galiellalactone have opposite optical rotations,
      demonstrating that the structure of the natural product is 1a.

PMID- 11529772
TI  - Asymmetric synthesis of trifluoromethylated allylic amines using alpha,beta
      unsaturated N-tert-butanesulfinimines.
AB  - [reaction: see text]. The trifluoromethide ion generated in situ from TMSCF(3)
      and TBAT (tetrabutylammonium triphenyldifluorosilicate), as well as TMAF
      (tetramethylammonium fluoride), adds to the alpha,beta-unsaturated N-tert
      butanesulfinimines exclusively in a 1,2 fashion with high diastereoselectivities,
      affording the first examples of chiral trifluoromethylated allylic amines.

PMID- 11529773
TI  - Ru-catalyzed cyclocarbonylation of alpha- and beta-allenic sulfonamides:
      synthesis of gamma- and delta-unsaturated lactams.
AB  - [reaction: see text]. The Ru-catalyzed cyclocarbonylation of alpha- or beta
      allenic sulfonamides in the presence of Ru(3)(CO)(12) (1 mol %) and Et(3)N (1.5
      equiv) under CO atmosphere (20 atm) in dioxane at 100 degrees C for 9 h gave
      heterocyclic gamma- and delta-unsaturated lactams in good yields.

PMID- 11529774
TI  - Synthesis of novel derivatives of 1,4,7-triazacyclononane.
AB  - [structure: see text]. The coordination environment of 1,4,7-triazacyclononane
      can be adapted, through sequential functionalization of two secondary amines, to
      generate ligands applicable in biomimetic studies. Two "amino acids" and an amino
      derivative have been prepared from 1,4,7-triazatricyclo[5.2.1.0(4,10)]decane.
      This synthon allows efficient attachment of one functional group to the
      macrocyclic ring, forming a monoamidinium salt. Hydrolysis generates a formyl
      derivative, which was further functionalized at the secondary amine and
      hydrolyzed in strong acid to generate ligands 1-3.

PMID- 11529775
TI  - Generating diversity in difluoromethyl ketone derivatives.
AB  - [reaction: see text]. Two consecutive palladium-catalyzed coupling reactions from
      a readily available difluoroenol stannane set the stage for the synthesis of a
      range of difluoro- and halodifluoromethyl ketones upon a variable aryl template.

PMID- 11529776
TI  - Stereocontrolled synthesis of the northern part of potent proteasome inhibitor
      TMC-95A.
AB  - [reaction: see text]. A protected version of the northern part of TMC-95A, a
      potent and selective proteasome inhibitor, was synthesized with full
      stereochemical control. Highlights of this synthesis include (i) a (Z)-selective
      Mizoroki-Heck reaction to construct the oxyindole portion, (ii) a
      diastereoselective epoxidation, (iii) a 6-endo selective epoxide opening by Boc
      carbonyl group to establish the stereochemistry of C6, and (iv) a 1,3-elimination
      reaction of the L-allo-threonine derivative under Mitsunobu conditions to afford
      the (Z)-1-propenylamine.

PMID- 11529777
TI  - Analogues of bleomycin: synthesis of conformationally rigid methylvalerates.
AB  - [structure: see text]. Several conformationally rigid analogues of the
      methylvalerate subunit contained within the linker domain of the antitumor
      antibiotic bleomycin have been prepared. These compounds have been protected in a
      fashion suitable for the solid-phase synthesis of bleomycin. Bleomycin congeners
      containing these analogues should facilitate a more detailed understanding of the
      nature of the conformational bend that the methylvalerate moiety is thought to
      impart to the natural product.

PMID- 11529778
TI  - Copper-mediated cross-coupling of functionalized arylmagnesium reagents with
      functionalized alkyl and benzylic halides.
AB  - [reaction: see text]. Functionalized arylmagnesium halides, prepared via an
      iodine-magnesium exchange, undergo a smooth cross-coupling reaction with
      functionalized primary alkyl iodides and benzylic bromides in the presence of
      CuCN.2LiCl, either in stoichiometric (with trimethyl phosphite as an additive) or
      catalytic quantities.

PMID- 11529779
TI  - A novel three-component butenolide synthesis.
AB  - [reaction: see text]. 5-Acylamino butenolides can be assembled by a
      multicomponent reaction (MCR) of isocyanides, glyoxals, and acetophosphonic acid
      diethylesters, followed by a intramolecular Wittig-type reaction. The reaction
      can be performed either in one pot or with the isolation of the intermediate
      Passerini product. This versatile reaction offers three independent inputs
      displayed in the final product. Applications in combinatorial chemistry and
      natural product synthesis can be envisioned.

PMID- 11529780
TI  - Enantioselective synthesis of a mitosane core assisted by diversity-based
      catalyst discovery.
AB  - [reaction: see text]. Synthesis of mitosane 1 in optically pure form is reported.
      A retrosynthetic plan that proceeds through racemic allylic alcohol 3 was carried
      out. This intermediate served as a test substrate for a rapid screen of a small
      library (152 members) of peptide-based kinetic resolution catalysts. Peptide 9
      was found to effect kinetic resolution with k(rel) = 27. Alcohol (-)-3 was then
      converted to optically pure (-)-1 in eight steps.

PMID- 11529781
TI  - Synthesis of diynes and tetraynes from in situ desilylation/dimerization of
      acetylenes.
AB  - [reaction: see text]. An efficient method for the in situ desilylation/oxidative
      dimerization of (trialkylsilyl)acetylenes is described. This protocol avoids the
      complications encountered with sensitive diynes by eliminating the deprotection
      and isolation steps. Various aromatic and alkyl diynes and tetraynes can be
      synthesized in a straightforward manner in good yields (82-99%) from TIPS
      protected acetylenes. This method facilitates the efficient synthesis of novel
      tetrayne-bridged acetylenic cyclophanes 6 and 7 in a direct manner.

PMID- 11529782
TI  - Multiple-electron transfer in a single step. Design and synthesis of highly
      charged cation-radical salts.
AB  - [structure: see text]. Macromolecules 1c and 2c bearing multiple redox-active
      sites are synthesized by an efficient palladium-catalyzed coupling of 2,5
      dimethoxytolylmagnesium bromide with readily available hexakis(4
      bromophenyl)benzene and tetrakis(4-bromophenyl)methane. These macromolecular
      electron donors undergo reversible oxidation at a constant potential of 1.15 V vs
      SCE to yield robust, multiply charged cation radicals that are isolated in pure
      form using SbCl(5) as an oxidant. These nanometer-size cation-radical salts are
      shown to act as efficient "electron sponges" toward a variety of electron donors.

PMID- 11529783
TI  - [4 + 3] Cycloaddition of cyclopropanone hemiacetals.
AB  - [reaction: see text]. Intermolecular and intramolecular [4 + 3] cycloaddition
      reactions of readily available cyclopropanone hemiacetals with furans are
      described.

PMID- 11529784
TI  - Facile three-component coupling procedure for the synthesis of substituted
      tetrahydroisoindole-1,3-diones from alpha,beta-unsaturated aldehydes.
AB  - [reaction: see text]. A new one-pot procedure for the efficient synthesis of a
      small library of amino-functionalized tetrahydroisoindole-1,3-dione derivatives
      was developed. This three-component coupling reaction comprises subsequent
      condensation and Diels-Alder reactions of ubiquitous available starting materials
      (alpha,beta-unsaturated aldehydes, amide, and maleimide). The synthesized
      compounds share a substituted tetrahydroisoindole motif in an endo fashion.

PMID- 11529785
TI  - Concise synthesis of a lactonamycin model system by diastereoselective
      dihydroxylation of a highly functionalized naphthoquinone.
AB  - [reaction: see text]. In this Letter, we describe an approach to the highly
      functionalized tetracycle 6, a model compound corresponding to the CDEF ring
      system contained in the recently discovered antibiotic lactonamycin. Our approach
      features an unprecedented, highly stereoselective dihydroxylation of quinone 13a,
      which leads directly to spirocyclic lactone 15, following acid-promoted
      deprotection/cyclization. The methodology described herein paves the way for a
      concise, highly diastereo- and enantioselective synthesis of the natural product.

PMID- 11529786
TI  - Stereoselective 1,2-additions of alpha-alkoxymethyllithiums to aldehydes.
AB  - [reaction: see text]. A chiral derivative of tributylstannylmethanol, readily
      prepared from L-valine, undergoes Sn-Li exchange to provide an alpha
      alkoxyorganolithium that adds to aldehydes with up to 91:9 dr. The
      diastereoselectivity depends on the solvent and alkyllithium used for
      transmetalation. Treatment of adducts with acid allowed recovery of the chiral
      auxiliary and diol with complete stereochemical integrity.

PMID- 11529787
TI  - Tandem double intramolecular [4 + 2]/[3 + 2] cycloadditions of nitroalkenes.
AB  - [reaction: see text]. A new class of tandem [4 + 2]/[3 + 2] cycloadditions of
      nitroalkenes is described in which both pericyclic processes are intramolecular.
      Two subclasses of intra [4 + 2]/intra [3 + 2] cycloadditions have been explored
      in which the dipolarophile is tethered at either C(5) or C(6) of the nitronate.
      For both families of precursors, the cycloadditions occur in good yield and are
      found to be highly regio- and stereoselective. This method converts linear
      polyenes to functionalized polycyclic systems bearing up to six stereogenic
      centers.

PMID- 11529788
TI  - A heterocycle-forming double michael reaction. [5 + 1] annulation route to highly
      substituted and functionalized piperidines.
AB  - [reaction: see text]. Nitrogen-containing tethered diacids, easily prepared by
      reductive alkylation of diethyl aminomalonate or ethyl cyanoglycinate, undergo
      double Michael reactions with 3-butyn-2-one to give highly functionalized and
      substituted piperidines (pipecolic acid derivatives) with surprisingly high
      stereoselectivity. The heterocyclic double Michael adducts can be induced to
      undergo further cyclizations to give a variety of azabicyclic and diazabicyclic
      compounds.

PMID- 11529789
TI  - Effect of allylic CH(3-n)F(n) groups (n = 1-3) on pi-facial diastereoselection.
AB  - [structure: see text]. Michael addition of various enolates toward gamma-CH(3
      n)F(n)-alpha,beta-unsaturated ketones (n = 1-3) was proven to smoothly furnish
      the 1,4-adducts with high si face selectivities which monotonously decreased by
      reduction in the number of fluorines. Although the Felkin-Anh model correctly
      anticipates the present stereochemical outcome only with E-acceptors, the
      hyperconjugative stabilization of transition states by electron donation from the
      allylic substituents (the Cieplak rule) successfully explains the pi-facial
      preference of both acceptors at least in a qualitative level.

PMID- 11529790
TI  - C-glycosides to fused polycyclic ethers. An efficient entry into the A-D ring
      system of gambierol.
AB  - [reaction: see text]. This Letter describes our use of C-glycosides to synthesize
      the A-D ring system of the marine ladder toxin gambierol in 20 steps.

PMID- 11529791
TI  - Synthesis of a broad array of highly functionalized, enantiomerically pure
      cyclohexanecarboxylic acid derivatives by microbial dihydroxylation of benzoic
      acid and subsequent oxidative and rearrangement reactions.
AB  - [reaction: see text]. We have found that the 1,2-dihydroxylation of benzoic acid
      with Alcaligenes eutrophus strain B9, first reported in 1971 by Reiner and
      Hegeman, is readily adapted for the preparation of tens to hundreds of grams of
      (1S,2R)-1,2-dihydroxycyclohexa-3,5-diene-1-carboxylic acid of >95% ee. This
      unique substrate undergoes many specific oxidative and rearrangement processes.
      Among these are transformations of unanticipated chemical novelty and many
      products that have not been previously described.

PMID- 11529792
TI  - A synthetic strategy for the cyclodepsipeptide core of the antitumor antibiotic
      verucopeptin.
AB  - [reaction: see text]. An efficient [2 + 2 + 2]-fragment condensation strategy is
      described for obtaining the cyclodepsipeptide core of verucopeptin. The 19
      membered macrocycle was established through a Carpino HATU mediated
      macrolactamization, which proceeded in good yield under high-dilution conditions.

PMID- 11529793
TI  - Novel polymer-bound chiral selenium electrophiles.
AB  - [reaction: see text]. Polymer-bound chiral electrophilic selenium reagents have
      been developed and applied to stereoselective selenenylation reactions of various
      alkenes. Different cleavage protocols allow further functionalization of the
      addition products leading to improvements in selenium-based solid-phase
      chemistry.

PMID- 11529794
TI  - Electrophilic cyclizations of vinylcyclopropanols to tethered aldehydes.
AB  - [reaction: see text]. The intramolecular, stereoselective addition of 1
      vinylcyclopropanols to tethered aldehydes has been achieved under mild
      conditions. Thus, sequential application of the titanium-mediated
      cyclopropanation of alpha,beta-unsaturated esters and the electrophilic
      cyclization of the aldehyde-tethered cyclopropanol products provides the facile
      formation of carbocyclic rings.

PMID- 11529797
TI  - Have the onset and tempo of puberty changed?

PMID- 11529798
TI  - Information technology and the future of child health care: a revolution is
      occurring.

PMID- 11529799
TI  - Computer simulation: a powerful tool for injury control.

PMID- 11529800
TI  - Threats of school violence in Pennsylvania after media coverage of the Columbine
      High School massacre: examining the role of imitation.
AB  - BACKGROUND: Following the April 20, 1999, massacre at Columbine High School,
      Littleton, Colo, school administrators, law enforcement officials, and the media
      reported a rash of successive bomb threats and threats of school violence that
      were attributed to imitation. OBJECTIVE: To establish that the clustering of
      threats of school violence following the Columbine massacre was initiated by
      imitation. DESIGN: A database of threats of school violence reported to the
      Pennsylvania Emergency Management Agency, Harrisburg, during the 50 days
      following the Columbine incident was examined to determine the daily frequency of
      threats. To determine factors that predict the occurrence of these threats,
      counties and school districts in which threats occurred were noted. RESULTS:
      Pennsylvania school districts reported 354 threats of school violence during the
      50 days after the Columbine massacre, far exceeding the 1 or 2 threats per year
      estimated by school administrators before 1999. The frequency of these threats
      over time demonstrated a crescendo-decrescendo pattern. Fifty-six percent of the
      threats were made on or before day 10 after the incident, and more than one third
      occurred on days 8, 9, and 10. Factors that predicted the likelihood of a
      school's receiving a threat after the massacre included a greater proportion of
      white students and larger school enrollment. CONCLUSIONS: Successive threats of
      violence follow a publicized act of school violence. The media should recognize
      that imitation threats can occur and craft their stories accordingly.

PMID- 11529801
TI  - How can information technology improve patient safety and reduce medication
      errors in children's health care?
AB  - BACKGROUND: Medication errors are common, costly, and injurious to patients.
      OBJECTIVE: To review the role of information technology in decreasing pediatric
      medication errors in both inpatient and outpatient settings. DESIGN: We performed
      a literature review of current information technology interventions. RESULTS:
      Several types of information technology will likely reduce the frequency of
      medication errors, although insufficient data exists for many technologies, and
      most available data come from adult settings. Computerized physician order entry
      with decision support substantially decreases the frequency of serious inpatient
      medication errors in adults. Certain other inpatient information technologies may
      be beneficial even though less evidence is currently available. These include
      computerized medication administration records, robots, automated pharmacy
      systems, bar coding, "smart" intravenous devices, and computerized discharge
      prescriptions and instructions. In the outpatient setting, where adherence is
      especially important, personalized Web pages and World Wide Web-based information
      have substantial potential. CONCLUSIONS: Medication errors are an important
      problem in pediatrics. Information technology interventions have great potential
      for reducing the frequency of errors. The magnitude of benefits may be even
      greater in pediatrics than in adult medicine because of the need for weight-based
      dosing. Further development, application, evaluation, and dissemination of
      pediatric-specific information technology interventions are essential.

PMID- 11529802
TI  - Computer simulation of stair falls to investigate scenarios in child abuse.
AB  - OBJECTIVES: To demonstrate the usefulness of computer simulation techniques in
      the investigation of pediatric stair falls. Since stair falls are a common
      falsely reported injury scenario in child abuse, our specific aim was to
      investigate the influence of stair characteristics on injury biomechanics of
      pediatric stair falls by using a computer simulation model. Our long-term goal is
      to use knowledge of biomechanics to aid in distinguishing between accidents and
      abuse. METHODS: A computer simulation model of a 3-year-old child falling down
      stairs was developed using commercially available simulation software. This model
      was used to investigate the influence that stair characteristics have on
      biomechanical measures associated with injury risk. Since femur fractures occur
      in unintentional and abuse scenarios, biomechanical measures were focused on the
      lower extremities. RESULTS: The number and slope of steps and stair surface
      friction and elasticity were found to affect biomechanical measures associated
      with injury risk. CONCLUSIONS: Computer simulation techniques are useful for
      investigating the biomechanics of stair falls. Using our simulation model, we
      determined that stair characteristics have an effect on potential for lower
      extremity injuries. Although absolute values of biomechanical measures should not
      be relied on in an unvalidated model such as this, relationships between accident
      environment factors and biomechanical measures can be studied through simulation.
      Future efforts will focus on model validation.

PMID- 11529803
TI  - Exposures and outcomes of children with urticaria seen in a pediatric practice
      based research network: a case-control study.
AB  - OBJECTIVES: (1) To determine the duration, outcome, and associated findings of
      urticaria in children seen by general pediatricians; (2) to compare the exposure
      to foods, medications, insect stings or bites, and the presence of other symptoms
      in children with urticaria with controls; (3) to determine general pediatricians'
      management of urticaria. DESIGN: Case-control. PARTICIPANTS: Children with
      urticaria seen by Utah Pediatric Practice Based Research Network members between
      August 1, 1999, and August 31, 2000. Control patients were matched for age and
      sex. MAIN OUTCOME MEASURES: Duration of urticaria; associated symptoms; personal
      and family history of atopy; medications; ingestion of peanuts, nuts, shellfish,
      tomatoes, strawberries, or eggs; being stung by an insect; suspected cause,
      diagnostic studies; treatment. RESULTS: Fifty-two cases and 47 controls were
      enrolled. The mean duration of urticaria was 8.9 days (range, 1-50 days).
      Seventeen patients (33%) and 1 control patient were taking antibiotics (odds
      ratio [OR], 22.3; 95% confidence interval [CI], 2.8-176; chi(2), P<.001).
      Fourteen patients and 5 controls had gastrointestinal symptoms (OR, 3.1; 95% CI,
      1.02-9.4; chi(2), P =.04). There were no differences between cases and controls
      for other symptoms, personal or family history of atopy, ingestion of the foods
      listed, insect sting, or other medications. A cause was suspected in 28 patients
      (54%): a "viral illness" (19%), antibiotics (15%), or a combination (35%).
      CONCLUSIONS: Patients were more likely than controls to be taking an antibiotic
      and were more likely to have a personal or family history of atopy or to report
      ingesting foods commonly associated with urticaria. A viral illness was the most
      common cause suspected by pediatricians.

PMID- 11529804
TI  - Secondary sexual characteristics in boys: estimates from the national health and
      nutrition examination survey III, 1988-1994.
AB  - BACKGROUND: Descriptive data on pubertal stages for a representative population
      of racially and ethnically diverse boys in the United States have not been
      published to our knowledge. OBJECTIVE: To determine at what ages boys in the
      United States reach each of the 5 sexual maturity stages for genital and pubic
      hair growth. DESIGN AND SETTING: Cross-sectional survey from the National Health
      and Nutrition Examination Survey III (NHANES III), 1988-1994. PARTICIPANTS: A
      population-based sample of 2114 boys aged 8 to 19 years representing 16 575 753
      boys according to NHANES III sampling strategies. The sample included white,
      African American, and Mexican American boys. MAIN OUTCOME MEASURES: Sexual
      maturity stages for genital maturation and pubic hair growth. RESULTS: The median
      (equivalent mean) ages at stage 2 for pubic hair development of white, African
      American, and Mexican American boys were 12.0 (95% confidence interval [CI], 11.7
      12.3), 11.2 (95% CI, 10.9-11.4), and 12.3 (95% CI, 12.1-12.6) years,
      respectively, and at stage 2 for genital growth were 10.1 (95% CI, 9.6-10.6), 9.5
      (95% CI, 8.9-10.0), and 10.4 (95% CI, 9.6-11.1) years, respectively. All 3 groups
      were significantly taller and heavier than boys in previous NHANES reports and
      showed earlier genital maturation and pubic hair growth than previous studies
      based on Tanner staging. Statistically significant differences among the 3
      racial/ethnic groups were found in the median ages of onset of pubic hair growth
      and genital development at stage 5 with and without controlling for height and
      weight, indicating an earlier age of attainment for the African American boys.
      CONCLUSIONS: The median (mean) ages at the onset of genital and pubic hair growth
      were younger than in past studies. Additional studies are required to further
      evaluate these findings and to explore the public health implications.

PMID- 11529806
TI  - Antenatal corticosteroids and newborn screening for congenital adrenal
      hyperplasia.
AB  - OBJECTIVE: To assess the effect of reported corticosteroid exposure on neonatal
      levels of 17-hydroxyprogesterone (17-OHP), the cortisol precursor used in newborn
      screening for congenital adrenal hyperplasia, in newborns weighing less than 2500
      g at birth. DESIGN: A retrospective study of newborns weighing less than 2500 g
      at birth and exposed to corticosteroids as reported on their newborn screening
      card compared with newborns weighing less than 2500 g at birth and reported as
      not exposed to corticosteroids. METHODS: Birth weight, gestational age, age at
      screening, special care information, and name of screening hospital were obtained
      from newborn screening cards for 16 115 newborns screened in Michigan during the
      first 3 months of 2000. Levels of 17-OHP, measured by fluoroimmunoassay, were
      obtained from Michigan's Newborn Screening Program database. RESULTS: The mean 17
      OHP level for the 69 low-birth-weight newborns in the corticosteroid-exposed
      group was 52 ng/mL, which was higher than that for the 771 low-birth-weight
      newborns in the unexposed group (35 ng/mL) (P<.001). Reported corticosteroid use
      did not decrease the number of expected borderline positive screening results for
      congenital adrenal hyperplasia (P>.05). Levels of 17-OHP varied by birth weight
      in corticosteroid-exposed and unexposed newborns. CONCLUSIONS: Corticosteroid
      exposure may not suppress screening 17-OHP levels. Therefore, newborn screening
      should not be delayed in premature newborns because of antenatal exposure to
      corticosteroids.

PMID- 11529805
TI  - Effectiveness of a home intervention for perceived child behavioral problems and
      parenting stress in children with in utero drug exposure.
AB  - OBJECTIVE: To determine if a home-based nurse intervention (INT), focusing on
      parenting education/skills and caregiver emotional support, reduces child
      behavioral problems and parenting stress in caregivers of in utero drug-exposed
      children. DESIGN: Randomized clinical trial of a home-based INT. SETTINGS: Two
      urban hospital newborn nurseries; homes of infants (the term infant is used
      interchangeably in this study with the term child to denote those from birth to
      the age of 36 months); and a research clinic in Baltimore, Md. PARTICIPANTS: In
      utero drug-exposed children and their caregivers (N = 100) were examined when the
      child was between the ages of 2 and 3 years. Two groups were studied: standard
      care (SC) (n = 51) and INT (n = 49). INTERVENTION: A home nurse INT consisting of
      16 home visits from birth to the age of 18 months to provide caregivers with
      emotional support and parenting education and to provide health monitoring for
      the infant. MAIN OUTCOME MEASURES: Scores on the Child Behavior Checklist and the
      Parenting Stress Index. RESULTS: Significantly more drug-exposed children in the
      SC group earned t scores indicative of significant emotional or behavioral
      problems than did children in the INT group on the Child Behavior Checklist Total
      (16 [31%] vs 7 [14%]; P =.04), Externalizing (19 [37%] vs 8 [16%]; P =.02), and
      Internalizing (14 [27%] vs. 6 [12%]; P =.05) scales and on the anxiety-depression
      subscale (16 [31%] vs. 5 [10%]; P =.009). There was a trend (P =.06) in more
      caregivers of children in the SC group reporting higher parenting distress than
      caregivers of children in the INT group. CONCLUSIONS: In utero drug-exposed
      children receiving a home-based nurse INT had significantly fewer behavioral
      problems than did in utero drug-exposed children receiving SC (P =.04).
      Furthermore, those caregivers receiving the home-based INT reported a trend
      toward lower total parenting distress compared with caregivers of children who
      received SC with no home visits.

PMID- 11529807
TI  - Cost-effectiveness of a school-based tobacco-use prevention program.
AB  - OBJECTIVE: To determine the cost-effectiveness of a school-based tobacco-use
      prevention program. DESIGN: Using data from the previously reported 2-year
      efficacy study of the Project Toward No Tobacco Use (TNT), we conducted a
      decision analysis to determine the cost-effectiveness of TNT. The benefits
      measured were life years (LYs) saved, quality-adjusted life years (QALYs) saved,
      and medical care costs saved, discounted at 3%. The costs measured were program
      costs. We quantified TNT's cost-effectiveness as cost per LY saved and cost per
      QALY saved. INTERVENTION: A 10-lesson curriculum designed to counteract social
      influences and misconceptions that lead to tobacco use was delivered by trained
      health educators to a cohort of 1234 seventh-grade students in 8 junior high
      schools. A 2-lesson booster session was delivered to the eighth-grade students in
      the second year. The efficacy evaluation was based on 770 ninth-grade students
      who participated in the program in the seventh and eighth grades and in both the
      baseline and the 2-year follow-up survey. RESULTS: Under base case assumptions,
      at an intervention cost of $16 403, TNT prevented an estimated 34.9 students from
      becoming established smokers. As a result, we could expect a saving of $13 316
      per LY saved and a saving of $8482 per QALY saved. Results showed TNT to be cost
      saving over a reasonable range of model parameter estimates. CONCLUSIONS: The TNT
      is highly cost-effective compared with other widely accepted prevention
      interventions. School-based prevention programs of this type warrant careful
      consideration by policy makers and program planners.

PMID- 11529808
TI  - The rotavirus vaccine's withdrawal and physicians' trust in vaccine safety
      mechanisms.
AB  - OBJECTIVE: To determine how the withdrawal from the market of the rotavirus
      vaccine has affected physicians' trust in vaccine safety mechanisms, future
      adherence to vaccine recommendations, and willingness to use a new rotavirus
      vaccine. DESIGN: National survey mailed to 1228 randomly selected pediatricians
      and family physicians. MAIN OUTCOME MEASURES: Confidence in vaccine safety
      mechanisms was defined by agreement with the statements that the system for
      determining vaccine safety before a vaccine is licensed works well and that the
      system for monitoring vaccine safety after vaccine licensure works well.
      Physicians who indicated that they would use a new rotavirus vaccine within 1
      year of licensure and recommendation by professional organizations were
      classified as "early adopters." Logistic regression was used to assess the
      relationship between trust in vaccine safety mechanisms and future early adoption
      of new rotavirus vaccines. RESULTS: Following the withdrawal of the rotavirus
      vaccine, 83% of respondents believed the postlicensure surveillance system works
      well to monitor vaccine safety, while 22% of respondents believed the
      prelicensure system works well to determine vaccine safety. After adjusting for
      physician specialty and years in practice, respondents who believed the
      prelicensure vaccine safety system works well were significantly more likely to
      be early adopters than those with less confidence in prelicensure studies
      (adjusted odds ratio, 2.2 [95% confidence interval, 1.3-3.6]). CONCLUSIONS:
      Physicians have different levels of trust in prelicensure studies that determine
      vaccine safety and postlicensure surveillance systems that monitor vaccine
      safety. Trust in prelicensure vaccine safety evaluations may be associated with
      early adherence to new vaccine recommendations.

PMID- 11529809
TI  - Reasons for pediatrician nonadherence to asthma guidelines.
AB  - BACKGROUND: The 1997 National Heart, Lung, and Blood Institute (NHLBI) asthma
      guidelines include recommendations on how to improve the quality of care for
      asthma. OBJECTIVE: To identify barriers to physician adherence to the NHLBI
      guidelines. DESIGN: Cross-sectional survey. PARTICIPANTS: A national random
      sample of 829 primary care pediatricians. MAIN OUTCOME MEASURES: Self-reported
      adherence to 4 components of the NHLBI guidelines (steroid prescription,
      instructing peak flow meter use, screening and counseling patients with asthma
      for smoking, and screening and counseling parents for smoking). We also collected
      information on physician demographics, practice characteristics, and possible
      barriers to adherence. We defined adherence as following a guideline component
      more than 90% of the time. RESULTS: The response rate was 55% (456/829). Most of
      the responding pediatricians were aware of the guidelines (88%) and reported
      having access to a copy of the guidelines (81%). Self-reported rates of adherence
      were between 39% and 53% for the guideline components. After controlling for
      demographics and other barriers, we found that nonadherence was associated with
      specific barriers for each guideline component: for corticosteroid prescription,
      lack of agreement (odds ratio [OR], 6.8; 95% confidence interval [CI], 3.2-14.4);
      for peak flow meter use, lack of self-efficacy (OR, 3.4; 95% CI, 1.9-6.1) and
      lack of outcome expectancy (OR, 4.7; 95% CI, 2.5-8.9); and for screening and
      counseling of patients and parents for smoking, lack of self-efficacy (OR, 3.8;
      95% CI, 1.7-6.2 and OR, 2.8; 95% CI, 1.3-5.9, respectively). CONCLUSIONS:
      Although pediatricians in this sample were aware of the NHLBI guidelines, a
      variety of barriers precluded their successful use. To improve NHLBI guideline
      adherence, tailored interventions that address the barriers characteristic of a
      given guideline component need to be implemented.

PMID- 11529810
TI  - Picture of the month. Denouement and discussion: alkaptonuria.

PMID- 11529811
TI  - Pathological case of the month. Diagnosis and discussion: pyogenic granuloma of
      the tongue.

PMID- 11529812
TI  - Radiological case of the month. Denouement and discussion: congenital esophageal
      duplication cyst as a rare cause of neonatal progressive stridor.

PMID- 11529813
TI  - Radiological case of the month. Denouement and discussion: synovial
      chondromatosis.

PMID- 11529814
TI  - The pediatric forum: confidentiality and adolescents' willingness to consent to
      sexually transmitted disease testing.

PMID- 11529815
TI  - The pediatric forum: trends in residents' perceptions of working conditions: 1989
      1999.

PMID- 11529816
TI  - The pediatric forum: neonatal hypermagnesemia: more causes and more symptoms.

PMID- 11529818
TI  - Statement of purpose revisited.

PMID- 11529819
TI  - Cost-benefit analysis of biopsy methods for suspicious mammographic lesions;
      discussion 994-5.
AB  - HYPOTHESIS: Stereotactic core biopsy (SCB) is more cost-effective than needle
      localized biopsy (NLB) for evaluation and treatment of mammographic lesions.
      DESIGN: A computer-generated mathematical model was developed based on clinical
      outcome modeling to estimate costs accrued during evaluation and treatment of
      suspicious mammographic lesions. Total costs were determined for evaluation and
      subsequent treatment of cancer when either SCB or NLB was used as the initial
      biopsy method. Cost was estimated by the cumulative work relative value units
      accrued. The risk of malignancy based on the Breast Imaging Reporting Data System
      (BIRADS) score and mammographic suspicion of ductal carcinoma in situ were varied
      to simulate common clinical scenarios. MAIN OUTCOME MEASURES: Total cost
      accumulated during evaluation and subsequent surgical therapy (if required).
      RESULTS: Evaluation of BIRADS 5 lesions (highly suggestive, risk of malignancy =
      90%) resulted in equivalent relative value units for both techniques (SCB, 15.54;
      NLB, 15.47). Evaluation of lesions highly suspicious for ductal carcinoma in situ
      yielded similar total treatment relative value units (SCB, 11.49; NLB, 10.17).
      Only for evaluation of BIRADS 4 lesions (suspicious abnormality, risk of
      malignancy = 34%) was SCB more cost-effective than NLB (SCB, 7.65 vs. NLB,
      15.66). CONCLUSIONS: No difference in cost-benefit was found when lesions highly
      suggestive of malignancy (BIRADS 5) or those suspicious for ductal carcinoma in
      situ were evaluated initially with SCB vs. NLB, thereby disproving the
      hypothesis. Only for intermediate-risk lesions (BIRADS 4) did initial evaluation
      with SCB yield a greater cost savings than with NLB.

PMID- 11529820
TI  - Trends in cardiac morbidity and mortality after endoluminal abdominal aortic
      aneurysm repair; discussion 999-1000.
AB  - HYPOTHESIS: The adverse cardiac event rate following endoluminal abdominal aortic
      aneurysm (EAAA) repair has decreased as experience in performing the procedure
      has increased. Aneurysm complexity affects the rate of adverse cardiac events.
      DESIGN AND PATIENTS: Data from 173 consecutive patients undergoing EAAA repair
      from 2 successive periods were compared. There were 82 patients in the early
      group (group 1) and 91 patients in the later group (group 2). MAIN OUTCOME
      MEASURES: Myocardial infarction, congestive heart failure, unstable angina, major
      dysrhythmias, death. RESULTS: The cardiac event rate was 8.5% for group 1 vs
      16.5% for group 2 (P =.16). Predictors of adverse cardiac events on multivariate
      analysis were the use of 4 or more graft extensions (P =.04), female sex (P
      =.01), and number of Eagle risk factors (P<.001). There were 2 postoperative
      deaths (2.4%) in group 1 and 4 (4.4%) in group 2 (P =.7). CONCLUSIONS: Following
      EAAA repair: (1) adverse cardiac events were found to correlate with use of 4 or
      more graft extensions, female sex, and the number of Eagle risk factors; (2)
      cardiac morbidity and mortality remain significant despite greater experience and
      improved technology; and (3) operative mortality remains acceptably low.

PMID- 11529821
TI  - Biochemical basis for the hypercoagulable state seen in Cushing syndrome;
      discussion 1006-7.
AB  - HYPOTHESIS: Cushing syndrome (CS) is associated with a hypercoagulable state that
      results in a 4-fold increase in the incidence of pulmonary embolism, deep venous
      thrombosis, and a 4-fold mortality rate compared with the general population. The
      incidence of CS in humans is approximately 2 to 5 per million per year, whereas
      in dogs it is much higher. The clinical complications of CS in humans are also
      manifested in dogs. We used a dog model of CS to better define the biochemical
      basis for the hypercoagulable state seen in the disease. DESIGN: A consecutive
      sample of dogs with CS and a cohort of healthy control dogs identified at a "well
      dog check" were enrolled. All dogs underwent blood assays to identify the levels
      of procoagulant factors, natural antithrombotics, and the degree of ongoing
      activation of the coagulation cascade. SETTING: University veterinary medical
      teaching hospital. RESULTS: A total of 86 dogs were enrolled, 56 with CS and 30
      control dogs. Levels of procoagulation factors II, V, VII, IX, X, XII, and
      fibrinogen were significantly increased in dogs with CS (P<.05). The natural
      antithrombotic antithrombin was significantly decreased in dogs with CS (P<.02).
      Thrombin-antithrombin complexes, a marker of subclinical thrombosis, were
      significantly increased in dogs with CS (P<.05). CONCLUSIONS: The hypercoagulable
      state of CS is demonstrated by an increase in thrombin-antithrombin complexes.
      This hypercoagulable state may be caused in part by (1) an elevation of
      procoagulant factors, and (2) a decrease in antithrombin. Because of the similar
      clinical and biochemical changes between dogs with CS and humans, this canine
      model may be a useful tool for the future study of the hypercoagulable state in
      CS.

PMID- 11529822
TI  - Usefulness of the triple test score for palpable breast masses; discussion 1012
      3.
AB  - HYPOTHESIS: The triple test score (TTS) is useful and accurate for evaluating
      palpable breast masses. DESIGN: Diagnostic test study. SETTING: University
      hospital multidisciplinary breast clinic. PATIENTS: Four hundred seventy-nine
      women with 484 palpable breast lesions evaluated by TTS from 1991 through July
      2000. MAIN OUTCOME MEASURES: Physical examination, mammography, and fine-needle
      aspiration were each assigned a score of 1, 2, or 3 for benign, suspicious, or
      malignant results; the TTS is the sum of these scores. The TTS has a minimum
      score of 3 (concordant benign) and a maximum score of 9 (concordant malignant).
      The TTS was correlated with subsequent histopathologic analysis or follow-up.
      INTERVENTIONS: The TTS was prospectively calculated for each mass. Lesions with a
      TTS greater than or equal to 5 were excised for histologic confirmation, whereas
      lesions with scores less than or equal to 4 were either excised (n = 60) or
      followed clinically (n = 255). RESULTS: All lesions with TTS less than or equal
      to 4 were benign on clinical follow-up, including 8 for which the fine-needle
      aspiration was the suspicious component. Of the 60 biopsied lesions, 51 were
      normal breast tissue, 4 showed fibrocystic change, 1 was a papilloma, and 4 were
      atypical hyperplasia. All lesions with a TTS greater than or equal to 6 (n = 130)
      were confirmed to be malignant on biopsy. Thus, a TTS less than or equal to 4 has
      a specificity of 100% and a TTS greater than or equal to 6 has a sensitivity of
      100%. Of the 39 lesions (8%) with scores of 5, 19 (49%) were malignant, and 20
      (51%) were benign. CONCLUSIONS: The TTS reliably guides evaluation and treatment
      of palpable breast masses. Masses scoring 3 or 4 are always benign. Masses with
      scores greater than or equal to 6 are malignant and should be treated
      accordingly. Confirmatory biopsy is required only for the 8% of the masses that
      receive a TTS of 5.

PMID- 11529823
TI  - Elevated body mass disrupts the barrier to gastroesophageal reflux; discussion
      1018-9.
AB  - HYPOTHESIS: Obesity impairs the antireflux function of a structurally intact
      barrier. DESIGN: Retrospective analysis of body mass index in patients with
      normal esophageal manometric findings but with symptomatic and objectively
      confirmed gastroesophageal reflux. SETTING: Specialist esophageal center.
      PATIENTS: Patients symptomatic and diagnostic for gastroesophageal reflux,
      referred between October 1, 1998, and June 30, 2000. Exclusion criteria were a
      defective barrier, motility disorders, or previous surgery. MAIN OUTCOME
      MEASURES: Reflux was defined and quantified using the DeMeester score, and body
      mass index was calculated. RESULTS: There was a strong correlation between body
      mass index and severity of gastroesophageal reflux. Patients who were overweight
      had significantly higher distal esophageal acid exposure. No significant
      difference in manometric findings was demonstrated between patients with normal
      weight and those who were overweight. CONCLUSION: The barrier to gastroesophageal
      reflux is rendered insufficient in patients who are overweight.

PMID- 11529824
TI  - Intraoperative ultrasound and preoperative localization detects all occult
      insulinomas; discussion 1025-6.
AB  - HYPOTHESIS: Preoperative invasive localization procedures with intraoperative
      ultrasound (IOUS) can result in successful surgical treatment of occult
      insulinomas when noninvasive imaging study results are equivocal or negative.
      DESIGN: Prospective study. SETTING: Tertiary care university hospital. PATIENTS:
      Thirty-seven consecutive patients with a biochemical diagnosis of insulinoma
      without multiple endocrine neoplasia (MEN). INTERVENTION: All patients underwent
      portal venous sampling (PVS) (n = 22) or calcium angiogram (n = 15) followed by
      surgery with palpation and IOUS (n = 37). MAIN OUTCOME MEASURE: Portal venous
      sampling, calcium angiogram, palpation, and IOUS were compared for accurate
      localization of insulinoma. RESULTS: All patients were cured of hypoglycemia
      after surgery. Portal venous sampling correctly localized tumors in 17 (77%) of
      22 patients. Calcium angiogram was correct in 13 (87%) of 15 patients. Palpation
      identified 24 (65%) of 37 tumors, and IOUS found 35 (95%) of 37 tumors. The 2
      tumors missed by IOUS were located in the tail of the pancreas and were resected
      based on regional localization alone. CONCLUSIONS: Intraoperative ultrasound is
      the single best localization study, but it will miss some tumors that regional
      localization can identify. Combining both modalities allowed surgical cure of all
      insulinomas in our study. Therefore, we recommend both IOUS and regional
      localization for insulinoma when preoperative imaging studies are equivocal.

PMID- 11529826
TI  - Indications and long-term outcome of treatment for benign hepatic tumors: a
      critical appraisal.
AB  - HYPOTHESIS: The natural history and clinical behavior of benign hepatic tumors
      during long-term follow-up may not justify primary surgical treatment. DESIGN:
      Retrospective study. SETTING: Tertiary referral center. PATIENTS: Two hundred
      eight patients diagnosed as having a benign liver tumor between January 1, 1979,
      and December 31, 1999. INTERVENTION: Seventy-four patients underwent hepatic
      surgery and 134 were managed conservatively by radiological follow-up. MAIN
      OUTCOME MEASURES: Symptoms and complications were assessed during management and
      follow-up. RESULTS: In the surgically treated population, the liver lesion was
      symptomatic in 47 patients (64%) and an incidental finding in 27 (36%). The
      operative morbidity and mortality were 27% (20 of 74 patients) and 3% (2 of 74
      patients), respectively. Overall, 28 (80%) of 35 patients with complaints were
      asymptomatic after surgery. During observation of the tumor in the conservatively
      managed group, 39 (87%) of 45 patients who presented with complaints were
      asymptomatic during a mean follow-up of 45 months; 6 patients had mild abdominal
      pain considered to be unrelated to the tumor. CONCLUSIONS: Conservative
      management of solid benign liver lesions such as focal nodular hyperplasia and
      hemangioma can be performed safely, irrespective of their size. We only advise
      surgery for liver lesions when there is an inability to exclude malignancy or in
      the case of severe complaints related to the tumor. Resection is always advocated
      in the case of a large hepatocellular adenoma (>5 cm) to reduce the risk of
      rupture and malignant degeneration.

PMID- 11529825
TI  - Outcome after intestinal transplantation: results from one center's 9-year
      experience; discussion 1031-2.
AB  - HYPOTHESIS: Outcomes after intestinal transplantation have improved during the
      past decade with refinements in surgical techniques as well as advances in
      immunosuppression and antimicrobial therapy. DESIGN: Retrospective analysis.
      SETTING: Tertiary care medical center, August 1991 through December 2000.
      PATIENTS: Adult (5) and pediatric (12) patients with intestinal failure. All
      developed complications from long-term total parenteral nutrition therapy. Median
      age was 8.6 years and median weight was 22 kg. INTERVENTIONS: Primary intestinal
      transplantation with (n = 14) or without (n = 3) the liver. MAIN OUTCOME
      MEASURES: Patient and graft survival, viral infections, rejection, and
      nutritional autonomy. RESULTS: Twenty-one intestinal grafts were transplanted
      into the 17 recipients. All donors were cadaveric and were matched by ABO blood
      group and size. Patient survival at 1 and 3 years was 63% and 55%, respectively.
      Death-censored graft survival at 1 and 3 years was 73% and 55%, respectively.
      There were 1.5 acute cellular rejection episodes per graft and 3 grafts were lost
      to rejection. Incidences of infection with the Epstein-Barr virus and
      cytomegalovirus were negligible with aggressive prophylaxis and preemptive
      therapy. Nutritional autonomy was achieved in 69% of grafts surviving more than
      30 days after intestinal transplantation. CONCLUSIONS: Intestinal transplantation
      is now the standard of therapy for patients with intestinal failure and
      complications resulting from total parenteral nutrition. Outcomes have markedly
      improved since initiation of the program. Aggressive immunosuppression as well as
      prophylaxis and preemptive antiviral therapy have led to low incidences of acute
      cellular rejection, Epstein-Barr virus, and cytomegalovirus. Finally, nutritional
      autonomy can be achieved after successful intestinal transplantation.

PMID- 11529827
TI  - The effects of glucocorticoid therapy on inflammatory responses to coronary
      artery bypass graft surgery.
AB  - HYPOTHESIS: Delayed or reduced polymorphonuclear leukocyte (PMN) apoptosis may
      contribute to prolongation of systemic inflammation after cardiopulmonary bypass.
      BACKGROUND/OBJECTIVE: Preoperative administration of glucocorticoids has been
      used ostensibly to attenuate the systemic inflammation associated with
      cardiopulmonary bypass. Therefore, this study evaluated, in patients undergoing
      cardiopulmonary bypass, the efficacy of glucocorticoids in restoring peripheral
      blood PMN apoptosis and modulating PMN surface receptors (CD95, tumor necrosis
      factor receptor [TNFR]) known to be involved in proapoptotic or antiapoptotic
      signal transduction. DESIGN: Randomized control study. SETTING: Medical school
      and affiliated tertiary care hospital. PATIENTS: Thirteen patients undergoing
      coronary artery bypass grafting. INTERVENTION: Patients were randomly assigned to
      the control group (n = 7) or to receive 1 g of methylprednisolone sodium
      succinate on anesthetic induction (n = 6). MAIN OUTCOME MEASURES: Blood samples
      were drawn before induction, 20 minutes after sternotomy and bypass, immediately
      postoperatively, and on postoperative day 1. Isolated PMNs were incubated for 6
      hours with or without the CD95 agonist CH 11. Polymorphonuclear leukocyte
      apoptosis was measured using propidium iodide-RNAase staining and flow cytometry.
      Levels of PMN cell-associated receptors (TNFR and CD95), cytokines (TNF-alpha,
      interleukin 6 [IL-6], IL-8, and IL-10), and soluble receptors (sTNFR1 and sTNFR2)
      were measured. RESULTS: In all 13 patients, spontaneous and Fas-mediated PMN
      apoptosis decreased more than 80% from baseline (P<.001) by postoperative day 1.
      Polymorphonuclear leukocyte CD95 increased (P<.003) by postoperative day 1
      compared with baseline, whereas PMN TNFR was unchanged. Methylprednisolone
      administration did not modulate PMN apoptosis or immunocyte receptor expression;
      however, such treatment did decrease postoperative IL-6 secretion (P<.001) and
      increase postoperative IL-10 secretion (P<.001). CONCLUSIONS: The complications
      of major surgery include persistent inflammation, which can lead to multisystem
      organ failure. Polymorphonuclear leukocyte resistance to apoptosis may contribute
      to this process. A single preoperative dose of glucocorticoids did not effect PMN
      apoptosis or receptor phenotype.

PMID- 11529828
TI  - The role of nephrectomy in the acutely injured.
AB  - HYPOTHESIS: The high mortality in patients who undergo nephrectomy after trauma
      is not secondary to the nephrectomy itself but is the consequence of a more
      severe constellation of injuries associated with renal injuries that require
      operative intervention. DESIGN: A retrospective review of all patients identified
      using International Classification of Diseases, Ninth Revision codes as having
      sustained renal injuries over a 62-month period. PATIENTS: Seventy-eight patients
      with renal injuries who underwent exploratory laparotomy were identified.
      METHODS: All medical records were reviewed for patient management, definitive
      care, and outcome. Based on outcome, patients were assigned to either the
      survivor or nonsurvivor group. For patients who underwent nephrectomy,
      intraoperative core temperature changes, estimated blood loss, and operative time
      were also reviewed. RESULTS: Seventy-eight patients with renal injuries who
      underwent exploratory laparotomy were identified. Twenty-nine patients underwent
      laparotomy with conservative management of the renal injury, of whom 5 (17.2%)
      died. Twelve patients had renal injuries repaired and all survived. Thirty-seven
      patients underwent nephrectomy, of whom 16 (43.2%) died. Compared with
      nephrectomy survivors, nephrectomy nonsurvivors had a significantly lower initial
      systolic blood pressure, higher Injury Severity Score, higher incidence of extra
      abdominal injuries, shorter operative duration, and higher estimated operative
      blood loss. The nephrectomy survivors' core temperature increased a mean of 0.5
      degrees C in the operating room, while the nephrectomy nonsurvivors' core
      temperature cooled a mean of 0.8 degrees C. CONCLUSIONS: Patients who undergo
      trauma nephrectomy tend to be severely injured and hemodynamically unstable and
      warrant nephrectomy as part of the damage control paradigm. That a high
      percentage of patients die after nephrectomy for trauma demonstrates the severity
      of the overall constellation of injury and is not a consequence of the
      nephrectomy itself.

PMID- 11529829
TI  - Totally implantable venous access devices implanted surgically: a retrospective
      study on early and late complications.
AB  - BACKGROUND: The techniques used for the implantation of totally implantable
      venous access devices (TIVADs) are the percutaneous approach and surgical
      cutdown; however, the choice is still controversial. HYPOTHESIS: The surgical
      cutdown approach may be beneficial to reduce the rate of complications. DESIGN:
      Retrospective review. SETTING: A university hospital and a tertiary referral
      center. PATIENTS: Patients undergoing a TIVAD implant at the First Surgical
      Clinic of the University of Catania in Catania, Italy, between January 1995 and
      December 1999, were considered for the study. All of the devices were implanted
      in an operating room under fluoroscopic control. The vein of choice was the
      cephalic vein. When the cephalic vein was not suitable for implantation, the
      external jugular vein or the axillary vein and its branches were used. The
      percutaneous approach to the subclavian vein or internal jugular vein was
      considered a last resort to implant a catheter. RESULTS: During the study period,
      346 TIVADs were implanted in 344 patients. The procedure was performed with local
      anesthesia in 341 cases (98.5%), and only 2 patients (0.6%) required sedation for
      psychological reasons. Three patients (0.9%) had their TIVAD placed during a
      laparotomy. In 326 patients (94.2%), the devices were implanted in the cephalic
      vein. In the remaining cases, other veins were used with surgical cutdown. The
      mean time for the procedure was 15 minutes. Percutaneous access was never used,
      and no early mechanical complications were recorded. Only 6 patients (1.8%) in
      our study group had late complications (1 case of migration of the catheter, 2
      cases of infection, and 3 cases of withdrawal occlusion). The catheter life
      ranged from 6 to 1487 days (mean time, 348 days). CONCLUSION: Our results confirm
      the safety, speed, and low cost of the open cutdown technique. This surgical
      procedure avoids both early and late complications that frequently occur with
      percutaneous access. Surgical cutdown should be considered the technique of
      choice to implant the TIVAD, especially in cancer patients.

PMID- 11529830
TI  - Melanoma of the clavicular region: multimodal treatment.
AB  - HYPOTHESIS: Treatment for melanoma that has metastasized to the supraclavicular
      nodes should be intensive and use a multimodality approach. DESIGN: Retrospective
      analysis of clinical records. SETTING: Six primary care centers, 2 of which were
      referral centers. PATIENTS: Eighteen patients diagnosed as having a rare pattern
      of advanced melanoma metastatic to the clavicular region. INTERVENTION: Combined
      radiotherapy, chemotherapy, and thorough surgical excision of the affected nodal
      basins. MAIN OUTCOME MEASURE: Length of survival from time of diagnosis and
      treatment to time of follow-up. RESULTS: Median survival among the 18 patients
      was 28 months with a 22% survival rate at 5 years after diagnosis. Among patients
      who received radiotherapy to the clavicular node basin, mean length of survival
      was 88.7 months with a 50% 5-year survival rate compared with a mean length of
      survival of 33.8 months and an 8.3% 5-year survival rate in patients who did not
      receive radiotherapy (P<.001). Mean survival among patients who had
      supraclavicular node dissection was 45.8 months with a 23.1% survival rate at 5
      years after diagnosis, compared with a mean survival of 52 months and a 20% 5
      year survival rate among patients who did not receive therapeutic
      lymphadenectomy. Of the 11 patients who had therapeutic lymphadenectomy, 2 also
      received radiotherapy to the supraclavicular nodal basin and continued to be
      disease-free at 82 and 130 months. All long-term survivors had been treated with
      intra-arterial chemotherapy. CONCLUSION: In a series of patients with malignant
      melanoma metastatic to the clavicular lymph nodes, multimodality treatment using
      radiotherapy, chemotherapy, and thorough surgical excision of affected nodal
      basins provided an appreciable 5-year survival rate.

PMID- 11529831
TI  - Predictive factors for metastatic involvement of nonsentinel nodes in patients
      with breast cancer.
AB  - BACKGROUND: The potential morbidity of an axillary lymph node dissection in
      patients with breast cancer can be avoided in patients with a negative sentinel
      node (SN). HYPOTHESIS: It may be possible to identify a subset of patients with a
      positive SN and without metastases in the remaining axillary lymph nodes. DESIGN:
      Case-control study. SETTING: Both primary and referral hospital care. PATIENTS:
      Data were studied for 255 consecutive patients with stage T1 or T2 breast cancer
      who had a successful identification of the SN. INTERVENTIONS: In patients with a
      positive SN, histological examination of all non-SNs that were negative by
      routine examination was the same as that for SNs (multiple sectioning and
      immunohistochemical analysis). MAIN OUTCOME MEASURES: The incidence of non-SN
      metastases was correlated with the surface area and number of SN metastases and
      primary tumor characteristics. A micrometastasis was defined as less than 1
      mm(2). RESULTS: Of 255 patients, the SN appeared to be positive in 93 (36%).
      Subsequent axillary lymph node dissection revealed positive non-SNs in 46
      patients (49%). Patients with a single positive SN and patients with metastases
      less than 1 mm(2) in the SN had significantly less non-SN involvement than
      patients with more than 1 positive SN (40% vs. 78%) and patients with
      macrometastases (27% vs. 49%). CONCLUSIONS: The incidence of non-SN metastases
      seemed to be related to the number of positive SNs and the size of SN metastases.
      However, in the group of patients with a positive SN, it was not possible to
      identify a subset of patients without non-SN metastases.

PMID- 11529832
TI  - Parathyroidectomy can improve bone mineral density in patients with symptomatic
      secondary hyperparathyroidism.
AB  - HYPOTHESIS: The recovery of osteoporosis or bone mineral density (BMD) after
      parathyroidectomy and autotransplantation can be improved in patients with
      symptomatic secondary hyperparathyroidism. DESIGN: Case series. SETTING: Tertiary
      referral center. PATIENTS: Forty-five patients with symptomatic secondary
      hyperparathyroidism who underwent total parathyroidectomy and autotransplantation
      were included. They were divided into an osteoporotic group (n = 20) and a
      nonosteoporotic group (n = 25) according to preoperative T scores less than -2.5
      at either the lumbar spine (L1-L4) or the femoral neck (FN). INTERVENTIONS: Serum
      levels of calcium, phosphorus, alkaline phosphatase, and intact parathyroid
      hormone were checked before surgery and 1 day, 1 week, and 3 months after
      surgery. The BMDs of the FN and L1-L4 were measured using dual-energy x-ray
      absorptiometry before surgery and 6 months after surgery. RESULTS: Patients with
      osteoporosis were older (mean +/- SD, 50.2 +/- 14.0 years) than those without
      osteoporosis (42.7 +/- 9.1 years) (P =.04). Except for bone fractures found in 2
      women in the osteoporotic group, there were no significant differences between
      the 2 groups in sex, clinical manifestations, duration of dialysis, weight of
      removed parathyroid tissue, and types of dialysis. Also, serum levels of calcium,
      phosphorus, alkaline phosphatase, and intact parathyroid hormone were similar in
      both groups. Both 1 day and 1 week after total parathyroidectomy and
      autotransplantation, serum levels of calcium and intact parathyroid hormone
      decreased rapidly and then gradually increased 3 months later; however, serum
      levels of alkaline phosphatase increased rapidly and then gradually decreased 3
      months later. Six months after parathyroidectomy, BMD, T score, and Z score at L1
      L4 and the FN increased significantly (P<.001). The increment was much better in
      the osteoporotic group than in the nonosteoporotic group (P<.001). Also,
      osteopenia or osteoporosis improved significantly after parathyroidectomy at both
      L1-L4 and the FN (P<.001 for both). CONCLUSION: Parathyroidectomy and
      autotransplantation can improve BMD of symptomatic secondary hyperparathyroidism
      at L1-L4 and the FN.

PMID- 11529833
TI  - Skin-sparing mastectomy with sentinel lymph node dissection: less is more.
AB  - Skin-sparing mastectomy is an emerging technique useful for patients with early
      stage breast cancer who are not candidates for breast conservation surgery and
      are candidates for immediate plastic surgery reconstruction of the breast.
      Coupled with sentinel node surgery to assess lymph node status, the goal of this
      technique is to achieve maximal breast and axillary tissue conservation without
      compromising thorough tumor resection.

PMID- 11529834
TI  - Surgery in the United Kingdom.
AB  - Surgery in the United Kingdom has been practiced for nearly 2000 years. It has
      evolved as a result of the experiences of warfare and the introduction of the
      scientific basis of surgery. The influence of the 4 surgical royal colleges in
      setting standards for training and examinations has ensured that new surgeons are
      equipped for independent practice as consultants. Responsibility for the National
      Health Service rests with the government, which determines the number of trainee
      surgeons in the various surgical specialties. Conflicts between service provision
      and training are highlighted, as are the pressures on academic institutions to
      meet the demands of clinical surgery. The government's National Health Service
      plan for England promises a major expansion in undergraduate places and an
      increase of 7500 consultants in all specialties by 2004. Time will tell if these
      changes lead to an improvement in surgical services and a reduction in waiting
      times.

PMID- 11529835
TI  - Endothelin plasma levels in burn patients.

PMID- 11529837
TI  - Image of the month. Carotid body tumor: intercarotid paraganglioma.

PMID- 11529838
TI  - Surgical reminiscences: Lester is coming.

PMID- 11529839
TI  - Moments in surgical history: orificial surgery.

PMID- 11529840
TI  - Howell Jolly bodies and a history of home-made bread.

PMID- 11529841
TI  - Reactive haemophagocytosis as a consequence of gluten enteropathy-associated
      intestinal non-Hodgkin's lymphoma with fatal outcome.

PMID- 11529842
TI  - The dysfibrinogenaemias.

PMID- 11529843
TI  - Venous thrombosis and anticoagulant therapy.

PMID- 11529844
TI  - The management of coumarin-induced over-anticoagulation Annotation.

PMID- 11529845
TI  - Quantification of TEL-AML1 transcript for minimal residual disease assessment in
      childhood acute lymphoblastic leukaemia.
AB  - Strategies currently used for residual disease detection in acute lymphoblastic
      leukaemia (ALL) rely on polymerase chain reaction (PCR) detection of
      immunoglobulin and T-cell receptor rearrangements. The TEL-AML1 fusion
      transcript, which is associated with t(12;21) (p13;q22), is found in 25% of
      childhood B-cell precursor ALL, and represents an interesting alternative target.
      We compared two methods for quantitating TEL-AML1 fusion transcripts: competitive
      PCR and real-time PCR. These techniques showed similar sensitivity (5 x 10(-5))
      and reproducibility. Giving highly correlated results, both techniques can be
      conveniently used for TEL-AML1 transcript quantification. The constancy of TEL
      AML1 expression was evaluated by measuring TEL-AML1 transcripts at different
      steps of the cell cycle, and in 21 cases of ALL at diagnosis. No major variation
      in TEL-AML1 expression was observed during the cell cycle or in 20/21 of the ALL
      patients. Residual disease was then determined after completion of induction
      therapy in 20 patients with a TEL-AML1-positive ALL. Seven patients out of 20
      (35%) were still positive, including two patients with high level of residual
      blasts (close to or beyond 10(-2)). When comparison was possible, results
      obtained using TEL-AML1 quantification were in accordance with those obtained
      using T-cell receptor rearrangements analysis.

PMID- 11529846
TI  - Significance of angiogenin plasma concentrations in patients with acute myeloid
      leukaemia and advanced myelodysplastic syndrome.
AB  - Human angiogenin is a potent inducer of angiogenesis. The association between
      angiogenin and cancer progression and poor outcome in solid tumours has been
      documented, but its significance in leukaemias has not been evaluated. We
      evaluated plasma angiogenin levels in 101 previously untreated patients with
      acute myeloid leukaemia (AML) (59 patients) and advanced myelodysplastic syndrome
      (MDS) (42 patients). Angiogenin levels were significantly higher in AML and
      advanced MDS patients than in healthy individuals (P < 0.00001). Angiogenin
      levels were also significantly higher in advanced MDS than in AML (P = 0.001).
      Higher levels of angiogenin correlated with prolonged survival periods in both
      AML and advanced MDS patients (P = 0.02 and 0.01 respectively). We found no
      correlation between angiogenin plasma level and various patient characteristics,
      including age, performance status, antecedent haematological disorder,
      haemoglobin, white blood cell and platelet counts, and poor prognosis
      cytogenetics. There was no significant correlation between angiogenin level and
      complete remission rate and duration in AML or advanced MDS patients. In
      multivariate analysis, angiogenin concentration retained its significance as a
      prognostic factor in AML (P = 0.03), together with age (P = 0.00007) and
      haemoglobin (P = 0.03).

PMID- 11529847
TI  - Detection and clinical significance of human acute myeloid leukaemia progenitors
      capable of long-term proliferation in vitro.
AB  - Acute myeloid leukaemia (AML) blasts within individual patients are heterogeneous
      in their surface antigen expression and proliferative ability suggesting that,
      subsequent to transformation, differentiation occurs creating a hierarchy of
      progenitors in AML. Cells that can produce AML colonies (colony forming units,
      CFU) in growth factor containing suspension cultures (SC) over 4-8 weeks have a
      phenotype similar to AML progenitors that engraft non-obese diabetic/severe
      combined immunodeficient (NOD/SCID) mice, but different from bulk AML blasts,
      suggesting that these AML SC-initiating cells (SC-IC) may be early progenitors.
      In this study, we evaluated culture conditions that provide for optimal growth of
      AML progenitors capable of long-term proliferation. The frequency of CFU, both
      initially and after 2-4 weeks of SC, varied over four logs between individual
      patients and was not related to French-American-British subtype. Using limiting
      dilution, the proliferative potential of individual SC-IC varied from 1 to 480
      CFU. The frequency of CFU from SC after > 4 weeks was prognostic for patient
      survival, and correlated with NOD/SCID engrafting ability. These results suggest
      the use of long-term culture as an assay for AML cells with leukaemia sustaining
      potential.

PMID- 11529848
TI  - Microsatellite instability occurs in defined subsets of patients with acute
      myeloblastic leukaemia.
AB  - Using a sensitive fluorescent-polymerase chain reaction technique we looked for
      microsatellite instability (MSI) as functional evidence of mismatch repair
      defects in 71 cases of acute myeloblastic leukaemia (AML). MSI was assessed at 11
      loci in matched leukaemic and constitutional DNA. Nine out of 71 patients (13%)
      were found to have MSI. Four of these patients had therapy-related leukaemia and
      the remaining five were all over the age of 60 years. There was a high incidence
      of adverse-risk cytogenetics in the patients with MSI, including abnormalities of
      chromosomes 5 and/or 7. Of the nine cases of t-AML included in this study, four
      (44%) had MSI. MSI was also seen in five of 51 cases (10%) over the age of 60
      years but not in any cases under the age of 60 years with de novo AML. Using a
      sensitive assay, our results suggest that MSI occurs in two subgroups of patients
      with AML: those with t-AML and the elderly (> 60 years), but is rare in younger
      patients.

PMID- 11529849
TI  - Fluorescent 5'-exonuclease assay for the absolute quantification of Wilms' tumour
      gene (WT1) mRNA: implications for monitoring human leukaemias.
AB  - The Wilms' tumour gene (WT1) has been suggested as a powerful parameter for
      molecular monitoring of minimal residual disease (MRD) in leukaemias. However,
      molecular monitoring via WT1 RNA levels is far from being routinely performed,
      which is possibly owing to the complex and inaccurate quantitative reverse
      transcription polymerase chain reaction (RT-PCR) procedures. Using a newly
      developed quantitative real time RT-PCR, we measured WT1 transcripts in
      peripheral blood leucocytes of patients with acute myeloid (AML), acute lymphoid
      (ALL) and chronic myeloid leukaemia (CML). While healthy blood donors did not
      show measurable amounts of WT1 transcripts, WT1 RNA levels were detectable in all
      types of leukaemia. Furthermore, intraindividual WT1 transcript kinetics were
      exclusively dependent on disease progression, treatment and subsequent disease
      outcome. Using this approach, we could distinguish between treatment response and
      failure within the first days of therapeutic intervention. Moreover, gradually
      rising WT1 levels over a period of weeks and months paralleled long-term disease
      progression and appeared to be a prognostic indicator for subsequent clinical
      relapse. A linear correlation between quantities of WT1 and bcr/abl fusion
      transcripts could be seen in CML. We conclude that quantitative assessment of WT1
      transcripts using real-time PCR is an appropriate method for molecular monitoring
      of AML, ALL and CML, and can be used independently for both short- and long-term
      monitoring of leukaemia patients.

PMID- 11529850
TI  - Autologous peripheral blood stem cell transplantation in patients with relapsed
      lymphoma results in accelerated haematopoietic reconstitution, improved quality
      of life and cost reduction compared with bone marrow transplantation: the Hovon
      22 study.
AB  - The present study analysed whether autologous peripheral blood stem cell
      transplantation (PSCT) improves engraftment, quality of life and cost
      effectiveness when compared with autologous bone marrow transplantation (ABMT).
      Relapsing progressive lymphoma patients (n = 204; non-Hodgkin's lymphoma n = 166;
      Hodgkin's disease n = 38) were, after induction treatment with the DHAP-VIM
      (cisplatin, cytarabine, dexamethasone, etoposide, ifosfamide, methotrexate)
      regimen, randomly (2:1) assigned to the harvest of granulocyte-macrophage colony
      stimulating factor-mobilized stem cells after the second DHAP course or
      autologous bone marrow cells before the second DHAP course. These stem cells were
      reinfused following high-dose myeloblative chemotherapy. After induction, 118
      patients obtained a partial or complete response and were eligible for
      randomization. In the PSCT arm (n = 76) significantly faster engraftment of
      neutrophils [> or = 0.1 and > or = 0.5 x 10(9)/l: 10.7 d (7-36, median, range),
      15 (9-45) versus 13 (8-25) and 26 (14-80), P < 0.01] and thrombocytes [> or = 20
      x 10(9)/l: 13 d (7-51) versus 18 (11-65), P < 0.01] were observed. In addition,
      significantly fewer transfusions of red blood cells [6 (0-23) versus 8 (2-24), P
      < 0.01] and platelets [4 (0-60) versus 8 (2-55), P = 0.01] were required in the
      PSCT arm. These findings were associated with a significant reduction in the
      median days of intravenous antibiotics in patients with fever [8.5 (0-30) versus
      14 (0-34), P = 0.04] and hospital stay [27 (8-51) versus 34 (24-78), P < 0.05].
      Quality of life demonstrated a significant difference in favour of the PSCT arm.
      Total transplantation costs were significantly lower in the PSCT arm [$13,954
      ($4913- 29,532) versus $17 668 ($10,170-44,083) P < 0.05], as a result of the
      reduced hospital stay and lower antibiotic costs. In summary, these results
      indicate that PSCT is superior to ABMT with regard to engraftment, supportive
      care, quality of life and cost.

PMID- 11529851
TI  - Deletions of D13S25, D13S319 and RB-1 mapping to 13q14.3 in T-cell prolymphocytic
      leukaemia.
AB  - Deletions of 13q14.3 are well known in several malignancies and are thought to be
      associated with tumour suppressor function. The RB-1 gene is a tumour suppressor
      gene, but other loci including D13S319 and D13S25 telomeric to this within
      13q14.3 are deleted in B-cell chronic lymphocytic leukaemia (B-CLL), multiple
      myeloma and non-Hodgkin's lymphoma, with varying clinical significance. The
      fluorescence in situ hybridization screening of 22 patients with T-prolymphocytic
      leukaemia (T-PLL) for deletions of 13q14.3 revealed loss of D13S25 in 17 cases
      (mean 40% range 13-98%), with 11 patients having at least a 20% deletion. Mapping
      the deletions for the RB-1, D13S319,and D13S25 loci revealed D13S25 as the most
      frequently deleted marker. However, patients with only the D13S25 deletion had
      low percentages of cells with the deletion (12-13%), suggesting that loss of
      D13S25 on its own may not provide sufficient growth advantage. The use of the YAC
      954c12, which maps immediately adjacent to D13S25, defined the telomeric border
      of the deletion in some of the cases. Inv(14)(q11q32) and t(14;14)(q11;q32) are
      characteristic of T-PLL, but are also observed in premalignant T-cell clones in
      patients with ataxia telangiectasia. Transition to overt leukaemia may result
      from loss of suppressor function. Thus, 13q14.3 deletions could contribute to the
      development of overt leukaemia in T-PLL, but the involvement of more than one
      gene in the region cannot be excluded.

PMID- 11529852
TI  - Intensification of salvage treatment with high-dose sequential chemotherapy
      improves the outcome of patients with refractory or relapsed aggressive non
      Hodgkin's lymphoma.
AB  - The aim of the present study was to retrospectively evaluate whether a high-dose
      sequential chemotherapy programme (HDS: cyclophosphamide, methotrexate,
      etoposide) administered prior to autologous transplantation could optimize the
      salvage of patients with refractory or relapsed aggressive non-Hodgkin's
      lymphoma. Between 1985 and 1999, 103 patients (median age 43 years, range 16-65)
      from eight Italian centres and one Swiss centre, with refractory (n = 38) or
      relapsed (n = 65) diffuse large B-cell and T-cell lymphoma, were treated using
      HDS followed by high-dose regimens with autologous haematopoietic stem cell
      transplantation. Eighty-three patients responded to the HDS regimen (81%, 95%
      C.I., 73- 88%) and 79 eventually achieved a complete response (CR) after
      autotransplantation (90%, 95% C.I., 81- 96%). None of 20 cases resistant to HDS
      attained CR. Treatment-related mortality was 4%. After a median follow-up of 24
      months (range 6-174 months), 3-year estimates of overall survival, event-free
      survival and disease-free survival were 47% (95% C.I., 36-59%), 44% (95% C.I., 34
      54%) and 64% (95% C.I., 50-74%) respectively. Multivariate analysis showed that
      chemosensitivity to HDS represented the strongest predictor of both CR and
      survival. This retrospective study shows that salvage treatment using HDS had
      relatively low toxicity and was associated with remarkable response rates,
      allowing further effective therapy with high-dose autograft programmes.

PMID- 11529853
TI  - Fludarabine plus cyclophosphamide is an efficient treatment for advanced chronic
      lymphocytic leukaemia (CLL): results of a phase II study of the German CLL Study
      Group.
AB  - The efficacy and toxicity of a combination of fludarabine and cyclophosphamide
      (FC) was evaluated in patients with B-cell chronic lymphocytic leukaemia (CLL).
      Between April 1997 and July 1998, 36 patients with CLL (median age 59 years)
      received a regimen that consisted of fludarabine 30 mg/m(2) in a 30-min IV
      infusion, d 1-3, and cyclophosphamide 250 mg/m(2) in a 30-min IV infusion on d 1
      3. Cycles were repeated every 28 d. Twenty-one patients had received between one
      and three different treatment regimens prior to the study, while 15 patients had
      received no prior therapy. The median Eastern Cooperative Oncology Group
      performance score was 1. One patient was at Binet stage A, 18 were stage B and 17
      patients were stage C. Objective responses, assessed according to the revised
      guidelines of the National Cancer Institute-sponsored Working Group, were
      recorded in 29 out of 32 assessable patients (90.6%). Twenty-four partial
      remissions and five complete remissions were observed. Two patients showed no
      change and one patient showed disease progression. At February 2000, three of the
      responders had relapsed. Severe neutropenia, anaemia and thrombocytopenia (Common
      Toxicity Criteria grade 3 and 4) were observed in 25, six and six patients
      (69.4%, 16.7% and 16.7%) respectively. Other side-effects were uncommon. No
      treatment-related deaths and no grade 3 or 4 infections occurred. We conclude
      that the combination of fludarabine and cyclophosphamide showed significant
      activity in patients with CLL. Myelosuppression was the major side-effect. These
      results warrant further study on the FC combination in randomized trials.

PMID- 11529854
TI  - Cytogenetic responses in high-risk myelodysplastic syndrome following low-dose
      treatment with the DNA methylation inhibitor 5-aza-2'-deoxycytidine.
AB  - Decitabine (5-aza-2'-deoxycytidine) acts as a powerful demethylating agent in
      vitro. Clinically, low-dose decitabine ameliorates cytopenias including induction
      of trilineage responses in approximately 50% of patients with high-risk
      myelodysplastic syndrome (MDS). We examined the incidence and kinetics of
      cytogenetic responses to decitabine in these patients. Of 115 successfully
      karyotyped patients, 61 (53%) had clonal chromosomal abnormalities prior to
      treatment. Major cytogenetic responses were observed in 19 patients (31% of those
      with abnormal cytogenetics, 17% of all patients by intention-to-treat) after a
      median of three courses (range, 2-6) until best cytogenetic response. Progressive
      decrease of the abnormal clone over time was also determined using fluorescence
      in situ hybridization (FISH) analysis in two patients. Median duration of
      cytogenetic responses was 7.5 months (range, 3-15). Analysis of response by the
      International Prognostic Scoring System (IPSS) cytogenetic risk groups revealed
      three out of five cytogenetic responses (60%) in the IPSS 'low-risk' group, 6 out
      of 30 with 'intermediate risk' (20%) and 10 out of 26 in the 'high-risk' group
      (38%). Median survival in these cytogenetic subgroups was 30, 8 and 13 months
      respectively. The relative risk of death in patients achieving a major
      cytogenetic response was 0.38 (95% confidence interval 0.17-0.88) compared with
      patients in whom the cytogenetically abnormal clone persisted (P = 0.0213). In
      conclusion, repeated courses of low-dose decitabine induce cytogenetic remissions
      in a substantial number of elderly MDS patients with pre-existing chromosomal
      abnormalties; these are associated with improved survival compared with patients
      in whom the cytogenetically abnormal clone persists. Patients with 'high-risk'
      chromosomal abnormalities may particularly benefit from this treatment.

PMID- 11529855
TI  - Successful treatment with cyclosporin A for myelodysplastic syndrome with
      erythroid hypoplasia associated with T-cell receptor gene rearrangements.
AB  - Myelodysplastic syndrome (MDS) with erythroid hypoplasia, a rare form of MDS, has
      not yet been clearly defined. We report four patients with MDS with erythroid
      hypoplasia who received immunosuppressive therapy. All were elderly, had severe
      transfusion-dependent anaemia, morphological evidence of myelodysplasia and a low
      percentage (3.2-13.6%) of erythroid precursors. Administration of cyclosporin A
      (CsA) improved their anaemia; all transfusion-dependent patients achieved
      transfusion-independence. An inverted CD4/8 ratio was seen in three patients who
      also demonstrated T-cell receptor (TCR)-beta and -gamma gene rearrangements by
      Southern blotting and clonality by polymerase chain reaction. Treatment with CsA
      can be an attractive alternative treatment for patients with MDS with erythroid
      hypoplasia, which may be associated with a clonal abnormality in T cells.

PMID- 11529856
TI  - Analysis of FGFR3 gene mutations in multiple myeloma patients with t(4;14).
AB  - The t(4;14)(p16.3;q32) in multiple myeloma (MM) leads to an apparent deregulation
      of the FGFR3 and WHSC1/MMSET genes. FGFR3 mutations, known to be associated with
      genetic skeletal disorders, have also been identified in a few cases of MM
      (mainly cell lines) with t(4;14). We investigated FGFR3 mutations in a series of
      53 MM cases; 11 cases with t(4;14) and FGFR3 overexpression were analysed using
      reverse transcription polymerase chain reaction, while the remaining cases were
      studied at DNA level. The Arg248Cys mutation, which is associated with some
      lethal forms of skeletal disorders, was found in one case with t(4;14). Our
      results indicate that FGFR3 mutations occur in only a small fraction of MM cases
      with t(4;14).

PMID- 11529857
TI  - Philadelphia (Ph) chromosome-positive chronic myeloid leukaemia relapsing as Ph
      negative leukaemia after allogeneic bone marrow transplantation.
AB  - Two patients with Philadelphia chromosome-positive (Ph(+)) chronic myeloid
      leukaemia (CML) relapsed 1.5 and 5 years after allogeneic bone marrow
      transplantation (BMT). Although the leukaemias were of recipient origin, t(9;22)
      could no longer be detected using conventional cytogenetics/fluorescence in situ
      hybridization or molecularly. Both patients responded to immunotherapy with donor
      lymphocytes/peripheral blood stem cells, although one patient ultimately relapsed
      again. These patients were similar to the occurrence of Ph(-) leukaemias
      previously described in Ph(+) CML after treatment with interferon or autologous
      BMT, and might be relevant in the pathogenesis and monitoring of treatment after
      BMT in CML.

PMID- 11529858
TI  - Severe factor VII deficiency with recurrent intracranial haemorrhages owing to
      double heterozygosity for a splice site mutation of an IVS4 and a novel nonsense
      mutation in exon 8 (Gln211-->Term).
AB  - Genetic analysis of a 10-month-old Japanese baby boy with recurrent intrathoracic
      bleeding, cerebral haemorrhages and gastrointestinal bleeding secondary to severe
      factor VII (FVII) deficiency revealed evidence of two distinct mutations of FVII:
      a splice site mutation of G-->A at nucleotide 6071 in the IVS4 splice site and a
      novel nonsense mutation (Gln211-->Term) in exon 8. His bleeding was difficult to
      control without prophylactic infusion of FVII. We detected a heterozygous splice
      site mutation of the IVS4 in his mother and a heterozygous nonsense mutation in
      exon 8 (Gln211-->Term) in his father. The parents' FVII levels are both 50% of
      normal controls. The FVII:C in plasma from the proband was < 1.5% of normal
      controls. FVII:antigen (Ag) was < 1% of normal controls, using a monoclonal
      antibody (mAb) hVII-B101/1 that specifically reacts with FVII epidermal growth
      factor 1 (EGF-1), and 5% of normal controls, using a rabbit polyclonal antibody
      against human FVII. After immunoadsorption with mAb hVII-B101/B1-Sepharose 4B,
      FVII levels of both the proband and his mother were 5% of normal controls; after
      immunoadsorption the FVII levels of normal subjects were < 1%. We hypothesize
      that secretion of a small amount of dysfunctional FVII lacking EGF-1 into the
      circulation accounts for this observation.

PMID- 11529859
TI  - Anti-tissue factor pathway inhibitor activity in patients with primary
      antiphospholipid syndrome.
AB  - The association between antiphospholipid antibodies and an increased risk of
      thrombosis in antiphospholipid syndrome (aPS) patients is probably caused by
      numerous mechanisms, including the effects of antibodies to phospholipid-binding
      proteins such as beta(2)-glycoprotein I and prothrombin. In this study, we
      investigated the inhibition of tissue factor pathway inhibitor (TFPI) in 33
      patients with primary antiphospholipid syndrome (PAPS). TFPI was measured in PAPS
      patients using an amidolytic assay, dependent on the generation of activated
      factor X (Fxa), and this was compared with 55 healthy subjects. Functional levels
      of TFPI (mean +/- SD) were significantly lower in PAPS patients (0.89 +/- 0.37
      U/ml) than the control group (1.05 +/- 0.15 U/ml) (P = 0.02). The difference was
      caused by a subset of five patients who had TFPI levels below the lower 99%
      confidence interval of the normal reference range, representing increased FXa
      generation in the assay system. IgG fractions were isolated from these five
      patients and five control subjects, then incorporated into normal plasma to
      measure FXa generation in the TFPI assay system. FXa generation was increased
      when polyclonal rabbit anti-human TFPI IgG (P < 0.0001) or PAPS IgG (P = 0.0001)
      were added to normal plasma, demonstrating inhibition of TFPI. The apparent anti
      TFPI activity demonstrated in the five subjects with PAPS in this study may
      represent a significant new mechanism for thrombosis in patients with aPS, as it
      implies that increased tissue factor FVIIa-mediated thrombin generation might
      occur.

PMID- 11529860
TI  - High factor VIII levels contribute to the thrombotic risk in families with factor
      V Leiden.
AB  - Factor V Leiden (FVL)-carrying relatives of selected patients with venous
      thromboembolism (VTE) have much higher venous thrombotic risks than FVL-carrying
      relatives of unselected consecutive patients with VTE. To find an explanation for
      this, we explored other risk factors of VTE, in particular the presence of high
      factor VIII levels, in a retrospective follow-up study. We assessed levels of
      factor VIII, factor IX, fibrinogen, protein C, protein S, antithrombin, the
      presence of prothrombin 20210A, and the occurrence of VTE in 61 first-degree
      relatives of 12 selected thrombophilic families harbouring FVL, and 183 first
      degree relatives of 47 unselected families of FVL carriers with a first VTE. In
      all families, FVL appeared to be an independent risk factor for VTE. Higher
      thrombosis incidence rates were found in carriers of both FVL and high factor
      VIII levels (> or = 150 IU/dl), while high levels of factor VIII appeared to be
      an independent thrombotic risk factor only in selected thrombophilic families.
      The fraction of individuals with more than one prothrombotic coagulation disorder
      was 10% higher in selected families. These results and the higher thrombotic
      risks we found in the thrombophilic families favour the hypothesis that other
      unknown co-existing genetic defects contribute to thrombophilia.

PMID- 11529861
TI  - The effect of human platelet alloantigen polymorphisms on the in vitro
      responsiveness to adrenaline and collagen.
AB  - A number of clinical studies have suggested that carriage of the low frequency
      allele (b) of the human platelet antigen 1 (HPA-1) system is a risk factor for
      coronary thrombosis. We have examined the effect of a series of HPA biallelic
      polymorphisms (systems -1, -2, -3 and -5) on the in vitro platelet aggregation in
      response to adrenaline and collagen in 30 healthy volunteers. There was a
      significantly higher prevalence (10 out of 18) of carriers of the HPA-1b
      polymorphism among subjects showing a > 50% aggregation response to adrenaline
      ('responders') than the prevalence (1/12) in 'non-responders' (P < 0.05).
      Platelets heterozygous for the HPA-1b polymorphism showed a significantly higher
      rate (slope) and greater extent (%) of adrenaline-induced aggregation than
      platelets not carrying the HPA-1b allele (P < 0.05). A greater extent of collagen
      induced aggregation was also demonstrated in HPA-1ab platelets (P < 0.05).
      Inhibition of adrenaline-induced aggregation following incubation with aspirin
      was greater (P < 0.01) in HPA-1ab than in HPA-1aa platelets. Collagen-induced
      aggregation was slower in carriers of the HPA-5b allele than in HPA-5aa subjects
      (P < 0.05). Polymorphisms of the HPA-2 and HPA-3 systems were not associated with
      different aggregation responses to either adrenaline or collagen. These results
      support the clinical observation that polymorphism HPA-1b may predispose to
      increased platelet thrombogenicity and suggest that the presence of polymorphism
      HPA-5b might render the platelet less reactive to collagen.

PMID- 11529862
TI  - Heparin-induced thrombocytopenia and thrombosis syndrome: in vivo cross
      reactivity with danaparoid and successful treatment with r-Hirudin.
AB  - Heparin-induced thrombocytopenia and thrombosis syndrome (HITTS) is an immune
      mediated drug reaction that occurs 5-14 d after initiation of heparin therapy and
      is a potentially life-threatening thrombotic complication. The antibody-heparin
      PF4 complexes cause platelet activation and generation of platelet
      microparticles. The need for anticoagulant treatment in asymptomatic
      thrombocytopenia is uncertain. However, treatment is warranted in HITTS, as
      illustrated in the case reported here. Danaparoid, r-Hirudin and argatroban are
      effective drugs. Danaparoid has a 10-50% in vitro cross-reactivity rate with the
      HIT antibodies, but has been proven to be clinically efficacious even in these
      cases. Here, we report a case of in vivo cross-reactivity with danaparoid, the
      patient showed an excellent recovery with r-Hirudin.

PMID- 11529863
TI  - Rapid genotyping of human platelet antigen 5 with fluorophore-labelled
      hybridization probes on the LightCycler.
AB  - Genotyping of human platelet antigens (HPAs) can be useful for the diagnosis and
      therapy of alloimmune thrombocytopenic syndromes such as neonatal alloimmune
      thrombocytopenic purpura, post-transfusion purpura and refractoriness to platelet
      transfusion therapy. We developed a single-tube method for HPA-5 genotyping on
      the LightCycler that combines rapid-cycle polymerase chain reaction with allele
      specific fluorescent probe melting for mutation detection. Our method is fast,
      robust and suitable for routine HPA-5 typing. This work extends recent studies on
      HPA-1 typing using the LightCycler.

PMID- 11529864
TI  - Persistent polyclonal B-cell lymphocytosis is an expansion of functional
      IgD(+)CD27(+) memory B cells.
AB  - Persistent polyclonal B-cell lymphocytosis (PPBL) is a rare disorder of unknown
      aetiology affecting predominantly young to middle-aged women. It is characterized
      by a polyclonal expansion of B cells, including typical binucleated lymphocytes,
      and is associated with the presence of the translocation t(14;18), involving the
      bcl-2 oncogene. The stage of differentiation of the B cells expanded in PPBL is
      not known. We analysed the immunophenotype of the expanded B-cell subset in five
      new patients with PPBL and found a large uniform expansion of a recently defined
      human memory B-cell population, IgD(+)CD27(+) memory B cells. After in vitro
      stimulation with interleukin 2 (IL-2) and Staphylococcus aureus Cowan strain I, B
      cells from PPBL patients produced high levels of IgM immunoglobulins, which is a
      characteristic feature of IgD(+)CD27(+) memory B cells. Using a quantitative real
      time polymerase chain reaction method, we found a high frequency of the
      translocation t(14;18) in the range of 1000-3000 per 106 B cells in PPBL
      patients. In contrast, a much smaller number of cells with a t(14;18) was found
      in B cells from healthy individuals. Our finding that PPBL is an accumulation of
      memory B cells further suggests that chronic antigeneic stimulation plays an
      important part in the pathogenesis of this disorder. This IgD(+)CD27(+) memory B
      cell population might harbour a certain number of 'physiological' t(14;18)
      translocations that increases as this population expands in PPBL patients and
      constitutes the majority of peripheral blood lymphocytes.

PMID- 11529865
TI  - Growth and immortalization of human myeloma cells in immunodeficient severe
      combined immunodeficiency mice: a preclinical model.
AB  - Human multiple myeloma (MM) purified tumour cells readily undergo apoptosis in
      vitro. Interleukin 6 (IL-6), a main growth factor of tumour cells, has enabled
      the development of IL-6-dependent MM cell lines. Recently, we developed anti
      gp130 monoclonal antibodies (mAbs), two of which (B1 + I2) were able to dimerize
      gp130 and replace IL-6 in vitro. We show here that the injection of B1 + I2 IL-6
      agonistic mAbs via the inguinal subcutaneous (SC) route efficiently produced
      tumours in severe combined immunodeficiency (SCID) mice grafted with IL-6
      dependent myeloma cell lines compared with either the intraperitoneal (IP) or
      abdominal surgical bursa (SB) routes. The SC tumour graft, together with Matrigel
      and vascular endothelial growth factor (VEGF), leads to a strong vascularization
      and early detection of serum human immunoglobulins (huIgs). SCID mice treated
      with B1 + I2 mAbs were injected with fresh MM cells from five patients, four of
      whom had consistent levels of huIgs, and tumour growth was present in two. For
      one patient, tumour plasma cells that were passed several times subcutaneously in
      new SCID mice, still expressed their initial markers after several months. They
      remained unable to grow in vitro in the presence of B1 + I2 or IL-6. The nature
      of the SCID factors involved and the triggered genes are under investigation.

PMID- 11529866
TI  - Evidence of a role for a non-matrix-type metalloproteinase activity in the
      shedding of syndecan-1 from human myeloma cells.
AB  - Syndecan-1 is a cell surface proteoglycan that is expressed on human myeloma
      cells and is thought to act as a co-receptor for certain extracellular matrix
      proteins and growth factors. The ectodomain of syndecan-1 is thought to be shed
      from the surface of myeloma cells, although the exact mechanism of release
      remains unclear. In this study, we used a panel of inhibitors to identify the
      class of proteinase responsible for shedding the soluble syndecan-1 ectodomain
      from human myeloma cells. Using enzyme-linked immunosorbent assay, flow cytometry
      and immunocytochemistry, we demonstrated that myeloma cell lines expressed
      syndecan-1 on their surface and that this was shed constitutively, but to a
      varying extent. In addition, phorbol 12-myristate 13-acetate (PMA), an activator
      of protein kinase C, stimulated a marked loss of cell surface syndecan-1 from
      each of the cell lines and this was associated with a corresponding increase in
      soluble syndecan-1. Inhibitors of serine and cysteine proteinases, and matrix
      type metalloproteinases, did not inhibit constitutive or PMA-stimulated syndecan
      1 shedding from JJN3 and RPMI 8226 cells. However, BB-94, a hydroxamate-based,
      broad-spectrum, metalloproteinase inhibitor, substantially suppressed
      constitutive and PMA-stimulated syndecan-1 loss from myeloma cells. These data
      indicate that a non-matrix-type metalloproteinase is responsible for syndecan-1
      shedding from the surface of myeloma cells.

PMID- 11529867
TI  - A prospective analysis of the pattern of immune reconstitution in a paediatric
      cohort following transplantation of positively selected human leucocyte antigen
      disparate haematopoietic stem cells from parental donors.
AB  - Transplantation of haematopoietic stem cells from human leucocyte antigen (HLA)
      disparate parental donors presents a promising new approach for the treatment of
      patients lacking a HLA-matched donor. Success against major obstacles such as
      graft-versus-host disease (GvHD) and graft rejection has recently been
      demonstrated, so that immune reconstitution is one of the prime factors that
      determines the long-term prognosis following transplantation. Twenty children
      transplanted with megadoses of highly purified CD34(+) haematopoietic stem cells
      after rigorous T-cell depletion were prospectively monitored for their immune
      reconstitution during the first post-transplant year. Natural killer (NK) cells
      showed a marked increase on d +30. T and B cells began to reconstitute on d +72
      and +68 respectively. During extended follow-up, their numbers and proliferative
      capacity upon mitogen stimulation continually increased. Early reconstituting T
      cells were predominantly of a primed, activated phenotype with severely skewed T
      cell receptor (TCR)-repertoire complexity. Naive T cells emerged 6 months post
      transplantation, paralleled by an increase in TCR-repertoire diversity. All
      patients self-maintained sufficient immunoglobulin levels after d +200. This
      study demonstrates that paediatric recipients of highly purified, haploidentical
      stem cells are able to reconstitute functioning T-, B- and NK-cell compartments
      within the first post-transplant year. This, together with the absence of
      significant GvHD, provides a strong indication for this approach to be considered
      in children who lack a HLA-matched donor.

PMID- 11529868
TI  - Prolonged ex vivo culture of cord blood CD34(+) cells facilitates myeloid and
      megakaryocytic engraftment in the non-obese diabetic severe combined
      immunodeficient mouse model.
AB  - A clinical goal for ex vivo expansion of cord blood (CB) CD34(+) cells is to
      shorten the period of neutropenia and thrombocytopenia following myeloablative
      therapy and transplantation. Prolongation of cytokine expansion leads to the
      production of greater numbers of cells, and should have an impact on neutrophil
      and platelet recovery. Furthermore, expansion of CD34(+) cells should support the
      continued production of neutrophils and platelets in the 6-week period following
      transplantation. We tested these hypotheses by characterization of the kinetics
      (human CD45(+) cells in the blood) and phenotype (CD45, CD34, CD61, CD33, CD19
      and CD3) of human engraftment in the non-obese diabetic severe combined
      immunodeficient mouse (NOD-SCID) following 7 or 14 d of ex vivo expansion of CB
      CD34(+) cells. Mice transplanted with 14 d cells showed greater percentages of
      human CD45(+) cells in the blood, bone marrow and spleen than mice transplanted
      with unexpanded cells or 7 d cells. Prolonging cytokine exposure of CD34(+) cells
      and transplantation with increasing numbers of input cells facilitated the
      production of absolute numbers of CD34(+), CD33(+), CD61(+) and CD19(+) cells in
      vivo. Furthermore, analysis of SCID engrafting potential showed that prolongation
      of culture duration facilitates in vivo expansion of CD45(+), CD34(+) and CD19(+)
      cells after transplantation. It is anticipated that prolonged (2 weeks) ex vivo
      culture of CB will have a beneficial clinical effect.

PMID- 11529870
TI  - Cord blood megakaryocytes do not complete maturation, as indicated by impaired
      establishment of endomitosis and low expression of G1/S cyclins upon
      thrombopoietin-induced differentiation.
AB  - Cord blood (CB) has successfully been used as a stem cell source for haemopoietic
      reconstitution. However, a significant delay in platelet engraftment is
      consistently found in CB versus adult peripheral blood (PB) or bone marrow
      transplants. We sought to determine whether or not CB megakaryocytes have reached
      terminal maturation and, hence, full thrombopoietic potential. A comparative
      analysis of megakaryocytes cultured from either CB or PB progenitors in the
      presence of thrombopoietin (TPO) showed a similar differentiation response,
      although proliferation was 2.4 times higher in CB than in PB cells. Importantly,
      the TPO-induced ploidy level was notably different: whereas 82.7% of CB
      megakaryocytes remained diploid (2N) at the end of the culture, more than 50% of
      PB megakaryocytes had reached a DNA content equal to or higher than 4N. Western
      blot and flow cytometry analyses revealed that only polyploid PB megakaryocytes
      expressed cyclins E, A and B, whereas cyclin D3 was detected in both fetal and
      adult megakaryocytic nuclei. These data suggest that establishment of endomitotic
      cycles is impaired in CB megakaryocytes, associated with a differential
      regulation of G1/S cell cycle factors. We believe that the relative immaturity of
      fetal megakaryocytes could be a contributing factor to the delayed platelet
      engraftment in cord blood transplantation.

PMID- 11529869
TI  - Transcript profiling of human dendritic cells maturation-induced under defined
      culture conditions: comparison of the effects of tumour necrosis factor alpha,
      soluble CD40 ligand trimer and interferon gamma.
AB  - Using cDNA arrays, we characterized patterns of gene expression in populations of
      human dendritic cells (DCs) produced for clinical use. Culture and maturation
      induction of myeloid adherent cells under serum-free conditions yielded DCs with
      phenotypes similar to those described in serum-based systems. Analysis of gene
      expression in DCs treated with tumour necrosis factor alpha, soluble CD40L trimer
      or interferon gamma, however, showed specific patterns for each factor examined.
      Our studies document the expression of several transcripts that have not hitherto
      been described in DCs and/or differentially regulated according to the
      differentiation state of the DCs, and suggest important functional differences
      among the DC populations examined. In addition, DC maturation directs changes in
      the levels of mRNA specific for transcriptional regulators that effect the
      production of cytokines (e.g. BCL-6, c-rel). Other changes observed, including
      alteration in the gene expression profile of adhesion molecules and chemokine
      receptors such as CD44H, CD 49B, Rantes R, CXCR5 and CD37, suggest differences in
      trafficking potential between the populations studied. This broad-based
      description of DC populations, produced under serum-free conditions, has enabled
      us to better define intermediate stages of DC maturation as well as the
      differentiation-inducing effects of cytokines on these cells.

PMID- 11529871
TI  - Calcium ionophore: a single reagent for the differentiation of primary human
      acute myelogenous leukaemia cells towards dendritic cells.
AB  - Blood monocytes and CD34(+) haemopoietic progenitor cells, as well as certain
      leukaemic cell lines, acquire characteristics of mature dendritic cells (DC)
      after stimulation with calcium ionophore (CI). We studied whether the in vitro
      treatment of primary human acute myelogenous leukaemia (AML) cells with CI leads
      to differentiation towards DC. Blast cells derived from nine AML patients were
      cultured in the presence of either CI or an established differentiation cocktail
      consisting of granulocyte-macrophage colony-stimulating factor plus interleukin 4
      and tumour necrosis factor-alpha for 5-7 d. Microscopic examination revealed that
      under both conditions, AML cells were shifted along the DC pathway. In seven out
      of nine cases, CI-cultivation led to a higher proportion of cells with dendritic
      morphology. The percentage of CD40 and CD86 expressing cells was significantly
      increased upon CI treatment compared with cytokine-cultured cells. DC molecules
      as CD80 and CD83 were up-regulated upon calcium mobilization of AML cells in four
      out of nine samples. In four cases, CI-treated stimulator cells induced an
      enhanced proliferative allogeneic T-cell response compared with cytokine-treated
      stimulator cells. In conclusion, these data demonstrate that CI treatment is an
      alternative in vitro strategy to differentiate human AML cells into DC.

PMID- 11529873
TI  - Identity of the tissue factor-inducing activity in human plasma.

PMID- 11529872
TI  - HFE mutations, iron deficiency and overload in 10,500 blood donors.
AB  - People with genetic haemochromatosis (GH) accumulate iron from excessive dietary
      absorption. In populations of northern European origin, over 90% of patients are
      homozygous for the C282Y mutation of the HFE gene. While about 1 in 200 people in
      the general population have this genotype the proportion who develop clinical
      haemochromatosis is not known. The influence of HFE genotype on iron status was
      investigated in 10 556 blood donors. The allele frequencies of the C282Y and H63D
      mutations were 8.23% and 15.3% respectively. Heterozygosity for C282Y occurred in
      1 in 7.9 donors, for H63D in 1 in 4.2 donors, and 1 in 42 were compound
      heterozygotes. Homozygosity for H63D occurred in 1 in 42 donors and 1 in 147 (72)
      were homozygous for C282Y. Mean values increased for transferrin saturation (TS)
      and serum ferritin (sFn), and decreased for unsaturated iron binding capacity
      (UIBC) in the order: donors lacking the mutations, H63D heterozygotes, C282Y
      heterozygotes, H63D homozygotes, compound heterozygotes and C282Y homozygotes,
      but serum ferritin (sFn) concentrations were no higher in H63D heterozygotes and
      C282Y heterozygous women than in donors lacking mutations. The percentage of
      donors failing the screening test for anaemia or of those with sFn < 15 microg/l
      did not differ among the genotype groups. C282Y and H63D heterozygotes and donors
      homozygous for H63D were at no greater risk of iron accumulation than donors
      lacking mutations, of whom 1 in 1200 had both a raised TS and sFn. The risk was
      higher for compound heterozygotes (1 in 80, P = 0.003) and for C282Y homozygotes
      (1 in 5, P < 0.0001). There was no correlation between sFn and either age or
      donation frequency in C282Y homozygotes. None of the 63 C282Y homozygous donors
      interviewed showed physical signs of overload or were aware of relatives with
      haemochromatosis. The Welsh Blood Service collects blood from about 140 000
      people each year including an estimated 950 who are homozygous for HFE C282Y.
      They are probably healthy and unaware of any family history of iron overload.

PMID- 11529874
TI  - Characterization of mutant clones lacking T-cell receptor alleles in a cell line
      from an adult T-cell leukaemia patient.

PMID- 11529875
TI  - Severe persistent neuropsychiatric toxicity after a human leucocyte antigen-non
      identical peripheral blood stem cell transplantation (total body irradiation,
      etoposide, thiotepa) and interleukin 2-based experimental therapy for poor
      prognosis relapse acute lymphoblastic leukaemia.

PMID- 11529876
TI  - Interpretation of inflammatory markers in feverish cancer patients with or
      without neutropenia at admission.

PMID- 11529879
TI  - Establishment of a tetraploid Meth-A cell line through polyploidization by
      demecolcine but not by staurosporine, K-252A and paclitaxel.
AB  - Polyploid cells are made by DNA reduplication without cell division, however, it
      is not easy to establish polyploid mammalian cell lines. It is worth studying the
      difference in cell character between hyperploid and parent cell lines. Meth-A
      cells were polyploidized by demecolcine, K-252a, staurosporine and paclitaxel.
      The cell-cycle responses of highly polyploid Meth-A cells after the removal of
      the drugs were examined by flow cytometry (FCM). Meth-A cells were highly
      polyploidized by these drugs. The polyploid Meth-A cells gradually decreased in
      ploidy after the drug release. A tetraploid Meth-A cell line was established only
      from the demecolcine-induced polyploid Meth-A cells. The duration of G1, S and
      G2/M phases of the tetraploid cell line were mostly the same as those of the
      parent diploid cells, except that the G2/M phase was 1.5 h longer. The chromosome
      number of tetraploid Meth-A cell line was about twice of the diploidy. A
      tetraploid Meth-A cell line was established.

PMID- 11529878
TI  - A study of death by anoikis in cultured epithelial cells.
AB  - BACKGROUND: Epithelial cells are critically dependent upon cell-matrix and cell
      cell adhesion for growth and survival. Anoikis is programmed cell death caused by
      disruption of cell-substrate adhesion in normal epithelial cells. METHODS: We
      studied the induction of anoikis in vitro in two cell lines; HaCaT and SW742.
      PI3K, JAK2 and PKC are key elements in signalling pathways regulating cell
      survival, and using specific inhibitors we also examined their potential role in
      the induction of anoikis. RESULTS: When prevented from adhesion by culture on
      polyHEMA, HaCaT cells underwent apoptosis selectively from the proliferating
      population; surviving cells underwent cell cycle arrest. In SW742 cells anoikis
      also occurred, but was balanced by increased cycling. The effects of specific
      kinase inhibitors indicated that both Janus kinase 2 and protein kinase C
      partially protect HaCaT cells from anoikis through inducing cell cycle arrest of
      surviving nonadherent cells; inhibition of Phosphatidylinositol 3-kinase did not
      induce cycling in HaCaTs prevented from adhesion but did stimulate anoikis. SW742
      cells showed markedly different responses: Janus kinase 2 inhibition activated
      apoptosis directly, Phosphatidylinositol 3-kinase inhibition stimulated both cell
      cycling and apoptosis, while protein kinase C inhibition stimulated cycling but
      inhibited apoptosis. CONCLUSIONS: Susceptibility to cell death in adhesion
      prevented epithelial cells may thus be regulated by signalling pathways involving
      Phosphatidylinositol 3-kinase, Janus kinase 2 and protein kinase C. The ability
      of epithelial tumour cells to invade and metastasize may therefore result from
      disruption of these pathways.

PMID- 11529881
TI  - Modulation of the expression of the Cip/Kip family of cyclin-dependent kinase
      inhibitors in foetal developing lungs of hamsters.
AB  - We examine the cell proliferation activity and expression of cyclin-dependent
      kinase inhibitors of the Cip/Kip family, p21Cip1, p27Kip1 and p57Kip2, in foetal
      hamster lungs to determine the expression patterns of the cyclin-dependent kinase
      inhibitors and to clarify the relationship between expression of the cyclin
      dependent kinase inhibitors and lung development. Foetal hamster lungs on
      gestational days 12.5-16 (the day of birth) and adult lungs were fixed in 4%
      paraformaldehyde. Frozen sections were immunostained for the cyclin-dependent
      kinase inhibitors, and examined by immunostaining for Ki-67 and bromodeoxyuridine
      to determine the proliferation activity of the foetal lungs. During the foetal
      period, cell proliferation activity, as analysed by Ki-67 or bromodeoxyuridine
      labelling, decreased with development of the lung. In contrast to the gradual
      decrease of cell proliferation activity, cells with p27Kip1 immunoreactivity
      increased with development. On the other hand, p21Cip1-positive cells were most
      prominent around gestational day 14.5, while after birth positive cells decreased
      markedly. A few p57Kip2-positive cells were detected in the bronchiolar
      epithelium on gestational day 14.5. Western blotting analyses confirmed these
      immunostaining patterns. Thus, the levels of the cyclin-dependent kinase
      inhibitors of the Cip/Kip family are modulated in the lungs during the foetal
      period, and each shows a unique expression pattern. The cyclin-dependent kinase
      inhibitors may play roles not only in regulating cell proliferation activity but
      also in regulating other functions such as differentiation in the lung during the
      foetal period.

PMID- 11529880
TI  - High levels of oestrogen receptor-alpha in tumorigenesis: inhibition of cell
      growth and angiogenic factors.
AB  - We previously found that the stable overexpression of oestrogen receptor-alpha in
      the human endothelial cell line ECV304* inhibits its growth in vitro, and that
      this inhibition is possibly mediated through a down-regulation of the vasoactive
      agents endothelin-1 and vascular endothelial growth factor. Here we show an in
      vivo growth-inhibitory effect of oestrogen receptor-alpha overexpression in
      tumours initiated in nude mice from the same clone of ECV304. In addition, we
      show that this growth inhibition is accompanied by an alphavbeta3-mediated
      inhibition of cell migration in vitro, and a down-regulation of the integrin
      alphavbeta3, vascular endothelial growth factor and vascularization in vivo. The
      levels of vascular endothelial growth factor and integrin alphavbeta3, through
      their effect on cell growth and migration, contribute to the process of
      angiogenesis and to the pathogenesis of atherosclerosis and cancer. The results
      shown here demonstrate that a higher level of oestrogen receptor-alpha in the
      cell, through its effect on certain angiogenic factors, may play a role in the
      control of angiogenesis.

PMID- 11529882
TI  - High sensitivity of human epidermal keratinocytes (HaCaT) to topoisomerase
      inhibitors.
AB  - In the panorama of the numerous established cell lines, the human keratinocyte
      line HaCaT has a very interesting feature, having a close similarity in
      functional competence to normal keratinocytes. This cell line has been used in
      many studies as a paradigm for epidermal cells and therefore we selected HaCaT as
      a cell model for investigating the activity of three antitopoisomerase drugs
      (Camptothecin, Doxorubicin, Ciprofloxacin) on in vitro cell growth. The effect
      was evaluated both by a 24-h cytotoxicity test and by a 7-day antiproliferation
      assay, in which the cell viability was assessed by an MTT (3-(4,5-dimethyl-2
      thiazolyl) 2,5-diphenil-2-H-tetrazolium bromide) test. DNA topoisomerase I was
      also partially purified from a nuclear extract of HaCaT cells, the level of topo
      I catalytic activity was measured by a pBR322 DNA relaxation assay and then the
      in vitro effect of antitopoisomerase drugs on the target enzyme was also
      assessed. The results indicated that the in vitro sensitivity of human epidermal
      HaCaT cells to antitopoisomerase drugs is comparable to that of many human tumour
      cell lines. HaCaT cells express a high level of topoisomerase I activity that is
      significantly inhibited by both Camptothecin and Doxorubicin and to a minor
      degree by Ciprofloxacin. A high correlation between the cell sensitivity to the
      antitopoisomerase I drug measured by the MTT test and the in vitro direct
      inhibition of HaCaT topoisomerase I was observed, suggesting that HaCaT cells can
      represent a very interesting model both for studying cellular pharmacokinetics of
      antineoplastic drugs on keratinocytes and for predicting possible secondary
      effects, exerted by these drugs on cutaneous cells, during treatment with
      chemotherapy.

PMID- 11529883
TI  - Cell migration and organization in the intestinal crypt using a lattice-free
      model.
AB  - We present a novel class of spatial models of cell movement and arrangement
      applied to the two-dimensional cellular organization of the intestinal crypt. The
      model differs from earlier approaches in using a dynamic movement on a lattice
      free cylindrical surface. Cell movement is a consequence of mitotic activity.
      Cells interact by viscoelastic forces. Voronoi tessellation permits simulations
      of individual cell boundaries. Simulations can be compared with experimental data
      obtained from cell scoring in sections. Simulation studies show that the model is
      consistent with the experimental results for the spatial distribution of
      labelling indices, mitotic indices and other observed phenomena using a fixed
      number of stem cells and a fixed number of transit cell divisions.

PMID- 11529884
TI  - The significance of immune responses to allergens in early life.

PMID- 11529885
TI  - NO2: the gas that won't go away.

PMID- 11529886
TI  - Granules of human eosinophilic leucocytes and their mobilization.

PMID- 11529887
TI  - Atopy and mutations of IL-12 receptor beta 2 chain gene.

PMID- 11529888
TI  - Lymphoproliferative responses in cord blood and at one year: no evidence for the
      effect of in utero exposure to dust mite allergens.
AB  - BACKGROUND: Maternal allergen exposure beyond the 22nd week of pregnancy may be
      important in foetal T cell priming. Allergen-specific cord blood mononuclear cell
      (CBMC) immunoproliferative responses without corresponding bacterial antigen
      responses (tetanus toxoid), have been suggested as evidence of in utero
      sensitization. OBJECTIVES: To investigate the relationship between
      lymphoproliferative responses at birth and at 1 year with maternal and 1-year
      infants house dust mite allergen exposure. METHODS: Home visits and dust sampling
      were performed by the 20th week of pregnancy, immediately after birth, and then
      at 1 years of age. Der p 1 was assayed using a two-site immunometric ELISA. CBMC
      immunoproliferative responses (AIM V serum-free medium; 1 x 105 cells/well) were
      measured for 225 neonates (171 had a high risk of atopy (HR)--both parents skin
      test positive; 59 had a low risk of atopy (LR) - both parents skin test negative,
      no history of atopy) by 3H-Thymidine (1microCi/well) incorporation after
      stimulation in primary culture with phytohaemagglutinin (PHA) (1 microg/mL),
      house dust mite [HDM] extract (30 microg/mL), immunopurified Der p 1 (30
      microg/mL), Tetanus toxoid (TT) (aluma free, 30 Lf/mL) or vehicle. Blood was
      collected from 144 infants at the age of 1 years and stimulated proliferative
      responses were assessed using the same procedure. RESULTS: PHA-stimulated
      lymphoproliferative response was significantly lower in HR compared to LR
      neonates (mean difference 38%, 95% CI 15%-54%; P = 0.003); significantly lower
      proportion of positive CBMC responses to HDM occurred in LR than in HR neonates
      (30.4% vs. 46.6%; P = 0.034). There was no relationship between Der p 1 levels in
      maternal bed and CBMC immunoproliferative responses, despite the 21 000-fold
      range of maternal Der p 1 exposure. No significant differences in magnitude, or
      in proportion of positive responses to any stimulant were observed between the
      neonates at low, medium or high tertile of allergen exposure. Immunoproliferative
      responses at birth were not predictive of 1-year PBMC responses. There was no
      relationship between maternal allergen exposure in pregnancy and 1-year PBMC
      proliferative responses. However, the proportion of positive proliferative
      responses at 1 years significantly increased with increasing infant Der p 1
      exposure at 1 years. CONCLUSION: These results indicate that the magnitude of
      immunoproliferative responses are unrelated to maternal mite allergen exposure
      and cannot be used as evidence for in utero sensitization to inhalant allergens.
      The immunoproliferative responses at 1 year seem to shift away from the
      genetically influenced responses at birth towards responses to specific
      stimulants which correlate with environmental exposure to those specific
      stimulants. These data support the concept of sensitization to inhalant allergens
      occurring in early life, but not in utero.

PMID- 11529889
TI  - The relationship between low level nitrogen dioxide exposure and child lung
      function after cold air challenge.
AB  - BACKGROUND: Nitrogen dioxide (NO(2)) or home gas appliance use has been
      inconsistently associated with adverse respiratory outcomes in childhood.
      OBJECTIVES: (i) To examine the contribution of home gas appliance type and
      personal NO(2) exposure. (ii) To examine the relationship between NO(2) exposure
      and child lung function and respiratory history. (iii) To assess whether these
      relationships vary by house dust mite sensitization status. METHODS: A cross
      sectional survey of 344 children (71% of the eligible group) with a mean age of
      9.1 years from four randomly selected schools in the Australian Capital Territory
      from July to September 1999. Study measurements included a parental
      questionnaire, NO(2) exposure by passive gas samplers, skin prick testing for 10
      aeroallergens and lung function at rest and after cold air challenge. RESULTS:
      Total NO(2) exposure was low with a mean concentration of 10.1 ppb. No
      associations were found between NO(2) exposure or gas appliance use and asthma,
      wheeze or baseline lung function. Personal NO(2) exposure was associated with a
      reduction in forced expiratory volume in one second (FEV1)/forced vital capacity
      (FVC) after cold air challenge (adjusted difference - 0.12% (- 0.23% to - 0.01%)
      per 1 ppb increase). After exclusion of children who had home heating changed
      because of asthma, gas heater use was also significantly associated with a
      reduction in this measure (adjusted difference - 2.0% (- 3.7% to - 0.2%)). There
      was some evidence that these reductions were greater among the non-mite
      sensitized children. CONCLUSIONS: The effect of low-level NO(2) exposure on these
      respiratory outcomes was not marked. The possible effect of low-level NO(2)
      exposure on non-specific bronchial reactivity requires confirmation. Future
      studies on NO(2) and respiratory health should include measures of house dust
      mite sensitization and bronchial hyper-responsiveness.

PMID- 11529890
TI  - Ambient ozone exposure is associated with eosinophil activation in healthy
      children.
AB  - BACKGROUND: Eosinophil activation is characteristic for allergic airways disease.
      However, eosinophilic airways inflammation has also been observed subsequent to
      ambient ozone exposure. METHODS: For a population sample of 877 children living
      at nine sites with different ozone exposure we measured urinary eosinophil
      protein X (U-EPX) as a marker of eosinophil activation. U-EPX was determined from
      a single spot urine sample during autumn 1997. Children were participants in a
      longitudinal study of ozone effects on lung function. RESULTS: The 5-95%
      percentiles of ozone exposure (30-day mean before test) were 11.8-51.5 p.p.b.
      (mean: 31.6 ppb). U-EPX was measured by radioimmunoassay and expressed as ratio
      to urinary creatinine (microg EPX/mmol creatinine). Log transformation was
      performed to achieve a normal distribution. LogU-EPX was associated with gender,
      a diagnosis of asthma and atopy (skin test sensitivity to any of seven
      aeroallergens). LogU-EPX increased with ozone exposure for all children. The
      medians of LogU-EPX according to the first-fourth quartiles of ozone exposure
      were: 1.82, 1.88, 1.95 and 2.03. For 172 non-asthmatic children who had spent the
      whole summer at their site corresponding figures were 1.57, 1.78, 2.07 and 2.13.
      In a multivariate model with logU-EPX being the dependent variable and adjusted
      for gender, site and atopy, ozone was found to be significant (estimate: 0.007
      microg/mmol creatinine per ppb ozone; SE:0.02; P < 0.001). CONCLUSION: Our
      observation supports the hypothesis that ozone in healthy children is associated
      with eosinophil inflammation, most likely in the airways.

PMID- 11529892
TI  - Prevalence of respiratory and atopic disorders in Chinese schoolchildren.
AB  - BACKGROUND: Epidemiological surveys have shown that the prevalence of asthma in
      the Asian population is relatively low. Within the Chinese population,
      schoolchildren from Hong Kong were found to have the highest rate of asthma.
      OBJECTIVE: To compare the prevalence of respiratory and atopic disorders, and to
      assess the role of atopy in the development of asthma, in Chinese schoolchildren
      from Hong Kong, Beijing and Guangzhou. METHODS: Community-based random samples of
      schoolchildren aged 9-11 years from three Chinese cities (Hong Kong, Beijing and
      Guangzhou) were recruited for study using the International Study of Asthma and
      Allergies in Childhood (ISAAC) Phase II protocol. Subjects were studied by
      parental questionnaires (n = 10902), skin-prick tests (n = 3479) and skin
      examination (n = 3479). RESULTS: The prevalence rates of current wheeze, speech
      limiting wheeze, rhinoconjunctivitis and flexural dermatitis were significantly
      more common in Hong Kong than in Beijing or Guangzhou. The atopy rate was also
      higher in Hong Kong (41.2%) than in Beijing (23.9%) or Guangzhou (30.8%). Atopy
      was strongly correlated with current wheeze (OR 7.74; 95% CI = 5.70-10.51).
      Subgroup analyses of children from Hong Kong revealed that children born in
      mainland China who had subsequently migrated to Hong Kong had a significantly
      lower rate of allergic symptoms and atopy than those children born in Hong Kong.
      CONCLUSION: Using a standardized written questionnaire along with a skin prick
      test and skin examination, we confirmed that the prevalence of asthma, allergic
      diseases and atopy was highest in schoolchildren from Hong Kong. Atopic
      sensitization is an important factor associated with asthma in Chinese children.

PMID- 11529891
TI  - Linkage to atopy on chromosome 19 in north-eastern Italian families with allergic
      asthma.
AB  - BACKGROUND: Allergic asthma is a multifactorial disease for which there is a
      widely assessed, although poorly understood, genetic involvement. Genome-wide
      screens reported evidence for linkage of allergic asthma-related phenotypes to
      several chromosomal locations. Markers on chromosome 19 have been linked to
      allergic asthma phenotypes in different populations in independent studies.
      OBJECTIVE: The aim of this study was to perform a genetic linkage analysis on
      chromosome 19 to search for DNA markers linked to phenotypes related to allergic
      asthma. METHODS: Using non-parametric multipoint linkage analysis on a total of
      22 random DNA markers in 2 stages, a sample of 111 families (542 subjects) from
      north-eastern Italy, recruited through an asthmatic allergic proband, was
      investigated. Phenotypes examined were: clinical asthma, total serum elevated
      IgE, skin prick test positivity, bronchial hyper-responsiveness, and atopy
      defined as skin prick test positivity and/or elevated IgE. Simulation studies
      were performed to confirm the significance of the results. RESULTS: A novel
      linkage of atopy and skin prick test positivity to marker D19S601 (19q13.3) was
      found. Modest evidence for linkage of atopy, skin prick test positivity, and IgE
      was also found to marker D19S591 (19p13.3). Simulation analysis for atopy gave an
      NPL-Z > 3.326 in 2 replicates out of 1000 (P = 0.002) for D19S601, and an NPL-Z >
      2.56 in 16 replicates out of 1000 (P = 0.016) for D19S591. CONCLUSIONS: On
      chromosome 19, suggestive linkage of atopy and skin prick test positivity with
      marker D19S601 (19q13.3) and modest evidence of linkage of marker D19S591
      (19p13.3) to the atopic phenotypes investigated were found. These results suggest
      that these regions may contain susceptibility loci associated to atopic
      phenotypes.

PMID- 11529893
TI  - Atopic asthma: differential activation phenotypes among memory T helper cells.
AB  - BACKGROUND: T cells have been implicated in the pathogenesis of atopic asthma. We
      have previously shown that memory T helper cells (CD4+CD45RO+) are preferentially
      activated relative to naive T helper cells (CD4+CD45RA+) after bronchial allergen
      challenge. However, specific T helper subpopulations that are activated in atopy
      and/or asthma remain undefined. OBJECTIVE: To determine the T helper
      subpopulations and activation phenotypes relevant to acute and stable asthma that
      may be common with or distinct from atopy. METHODS: Two groups of atopic
      asthmatics (ten acute and nine stable asthmatics) and two non-asthmatic groups
      (14 non-asthmatic atopics and eight normal non-atopic controls) were analysed.
      Ten acute asthmatics were assessed in the emergency room during an acute episode
      (FEV1 43.6% +/- 18.4). Nine stable asthmatics were assessed during a symptom-free
      period (FEV1 85% +/- 6). Using multiple colour flow cytometry we analysed T cell
      subpopulations and the expression of IL-2-receptor (IL-2R) and MHC-class II
      antigens (MHC II) on naive and memory T helper cells in the peripheral blood of
      asthmatic and non-asthmatic groups. RESULTS: Atopic asthmatics (acute and stable)
      had an increased percentage of memory T helper cells expressing IL-2R compared
      with normal non-atopics (mean SD 16.1 +/- 6%, 12.4 +/- 2% and 7.7 +/- 1.8%, P <
      0.05) but not compared with non-asthmatic atopics (10 +/- 3.5%). Naive T helper
      cells had low expression of IL-2R and MHC II in all four groups. MHC II antigen
      expression was increased in memory T helper cells of asthmatics (acute and
      stable) compared with normal non-atopics (13.9 +/- 7.5, 10.6 +/- 5 and 4.9 +/-
      2.5, P < 0.05) but not compared with non-asthmatic atopics (7.92 4). A novel
      finding was that IL-2R and the MHC II molecules were mainly expressed in non
      overlapping populations and coexpression was found predominantly on memory T
      helper cells. Asthmatics (acute and stable) had higher proportion of double
      positive memory T helper cells (IL-2R+MHC II+) compared with both non-asthmatic
      groups (P < 0.05). CONCLUSIONS: We demonstrate a differential expression of IL
      2R+ and MCH II+ on CD45RO+ T helper cells that would suggest that there are three
      subsets of activated memory T helper cells in asthmatics. Two non-overlapping IL
      2R+ or MHC II+ CD45RO+ T helper cells and a third subpopulation of activated
      cells that coexpress IL-2R and MHC II (double positives). This latter
      subpopulation is significantly higher in asthmatics (acute or stable) compared
      with both non-asthmatic groups, suggesting a specific T helper activation
      phenotype distinct to atopic asthmatics as compared with atopic non-asthmatics.

PMID- 11529894
TI  - Expression of costimulatory CD80/CD86-CD28/CD152 molecules in nasal mucosa of
      patients with perennial allergic rhinitis.
AB  - BACKGROUND: B7 molecules (CD80, CD86) and their counter-receptors, CD28 and CD152
      (CTLA-4), play an important role in T cell-mediated immune responses. We
      previously demonstrated that B7 molecules are selectively up-regulated not only
      on B cells but also on T cells from the peripheral blood mononuclear cells of
      patients with perennial rhinitis cultured with allergen. However, the expression
      of CD80/CD86 molecules and their counter-receptors in nasal mucosa, the actual
      inflammatory site of allergic rhinitis, has not yet been clarified. PATIENTS AND
      METHODS: Inferior turbinates from patients with either allergy to house dust or
      non-allergic rhinitis were excised and immunohistologically stained. In addition,
      the inferior turbinates were challenged with paper discs containing extracts of
      house dust and subsequently excised. Samples were double stained with
      immunofluorescent-labelled antibody to identify cells bearing CD86. RESULTS:
      Without the nasal provocation, only the expression of CD86 was increased in nasal
      mucosa of patients with allergic rhinitis compared with those with non-allergic
      rhinitis. However, following the nasal provocation with house dust, not only
      CD86, but also CD80, CD28, and CD152 were significantly expressed in allergic
      patients. Immunofluorescent double staining revealed CD86 expression in CD19,
      CD1a, CD14 and CD3 lymphocytes. CONCLUSION: These results indicate that the
      expression of CD80/CD86 molecules and their counter-receptors is induced in
      allergic patients following nasal provocation with allergen, suggesting a local
      amplification of allergen-specific immune responses in perennial rhinitis.

PMID- 11529895
TI  - Early introduction of cereals into children's diets as a risk-factor for grass
      pollen asthma.
AB  - BACKGROUND: The prevalence of asthma has increased from the 1950s to the 1990s.
      The relationship between diet and asthma is an area of controversy that has never
      been fully evaluated. Attempts at dietary prevention of asthma have produced
      conflicting results. We have recently identified allergens from cereals that show
      cross-reactivity with proteins in grass pollen. An early intake of cereals in the
      diet during early life might cause IgE sensitization to cereals. It is not known
      whether such sensitization predisposes the development of allergy to pollen.
      METHODS: To test this hypothesis, a cross-sectional study and an observational
      case-control analysis of reviewed data were carried out on 16381 patients who had
      been admitted to our Allergy Unit between 1989 and 1999. All the patients
      underwent allergy tests to identify asthma risk-factors. All information in our
      data base was analysed using the SPSS computer system. RESULTS: There has been an
      increase of 7.8% in incidences of allergic asthma and a 7.3% increase in asthma
      due to grass pollen in the last decade. Grass-pollen asthma was associated with
      sensitization to cereals. The early introduction of cereals in the diet of
      children was found to be a risk factor for grass-pollen asthma (OR = 5.95; 95% CI
      3.89-9.10). CONCLUSIONS: These findings document the progression of allergic
      asthma during a decade in a large sample of people who were influenced by similar
      environmental conditions and studied with the same diagnostic methods. This study
      represents the largest database of patients in which a common food is shown to be
      a risk factor for asthma.

PMID- 11529896
TI  - Identification of IgE and IgG binding epitopes on beta- and kappa-casein in cow's
      milk allergic patients.
AB  - BACKGROUND: Cow's milk allergy (CMA) affects 2.5% of children aged less than 2
      years of age. Although beta- and kappa-casein are considered among the major
      allergens responsible for CMA, no data are available on their allergenic epitopes
      in humans. OBJECTIVE: The aim of the study was to identify IgE- and IgG-binding
      epitopes on beta- and kappa-casein and to determine whether the pattern of
      epitope recognition is associated with the natural history of CMA. METHODS:
      Overlapping decapeptides representing the entire length of beta- and kappa
      casein, respectively, were synthesized on a cellulose-derivatized membrane. Sera
      from 15 milk-allergic children, 4-18 years of age, with high levels of specific
      IgE antibodies to cow's milk were used to identify IgE- and IgG-binding epitopes.
      In addition, IgE epitopes were screened with pooled or individual sera from
      younger patients aged less than 3 years and who had low levels of specific serum
      IgE, who are likely to outgrow CMA. RESULTS: Six major and three minor IgE
      binding epitopes, as well as eight major and one minor IgG binding regions, were
      identified on beta-casein. Eight major IgE-binding epitopes, as well as two major
      and two minor IgG-binding epitopes, were detected on kappa-casein. Three of the
      IgE binding regions on beta-casein and six on kappa-casein were recognized by the
      majority of patients in the older age group, but not by the younger patients.
      CONCLUSION: Information regarding the immunodominant epitopes in beta- and kappa
      casein may be important for understanding the pathophysiology and natural history
      of CMA. Differences in epitope recognition may be useful in identifying children
      who will have persistent milk hypersensitivity.

PMID- 11529897
TI  - IFN-gamma production in response to IL-18 or IL-12 stimulation by peripheral
      blood mononuclear cells of atopic patients.
AB  - BACKGROUND: Several studies have shown that interleukin (IL)-4 and interferon
      gamma (IFN-gamma) are important for the regulation of immunoglobulin E (IgE)
      production and that IL-18 and IL-12 induce IFN-gamma. OBJECTIVE: IFN-gamma
      production in response to IL-18 or IL-12 stimulation was investigated in
      peripheral blood mononuclear cells (PBMCs) of atopic patients with various levels
      of serum IgE. METHODS: Cytokine production from PBMCs was measured following
      stimulation with a non-specific stimulator (phytohemagglutinin: PHA), IL-18 or IL
      12 in 12 healthy controls and 26 atopic patients with various serum IgE levels.
      RESULTS: IFN-gamma production by IL-18-stimulated PBMCs was positively correlated
      with IFN-gamma production by IL-12-stimulated PBMCs (P < 0.05). However some
      atopic patients showed discrepancy between the levels of IFN-gamma production
      stimulated by IL-12 and by IL-18. CONCLUSIONS: The results shown here suggest the
      presence of abnormalities in the IL-12 and/or IL-18 signalling pathways, such as
      genetic defects in the atopic patients.

PMID- 11529898
TI  - Quantification in mass units of group 1 grass allergens by a monoclonal antibody
      based sandwich ELISA.
AB  - BACKGROUND: Grass pollen extracts currently used for allergy diagnosis and
      immunotherapy are a complex mixture of proteins of which only a few have
      allergenic activity. Lol p 1 is one of the most important allergens in grass
      pollen extracts. OBJECTIVES: To develop a two-site enzyme-linked immunosorbent
      assay for the quantification of Lol p 1 and other group 1 allergens from grass
      species, and to assess its suitability for quantifying this group of allergens.
      METHODS: Balb/c mice immunized with recombinant Lol p 1 were used for the
      production of monoclonal antibodies. Screening of hybridomas was performed by
      direct ELISA, and selected monoclonal antibodies were immobilized on ELISA plates
      and incubated with samples containing group 1 allergens. Bound allergens were
      detected by a combination of biotinylated Lol p 1-specific monoclonal antibody
      and peroxidase-streptavidin conjugate. RESULTS: The assay is based on three Lol p
      1-specific monoclonal antibodies with different epitope specificities. The
      optimized ELISA measured Lol p 1 concentrations ranging from 125 to 1000 ng/mL
      and could quantify group 1 allergen from grass species belonging to the Pooidea
      subfamily. The assay does not depend on anti-sera production or availability of
      human sera and thus reactives can be produced in unlimited amounts. CONCLUSION:
      This sensitive and specific Lol p 1 assay will be helpful both for quantifying
      the group 1 allergen content of Pooideae pollen extracts intended for clinical
      use and for studying cross-reactivities among pollen extracts.

PMID- 11529900
TI  - cDNA cloning and molecular identification of the major oyster allergen from the
      Pacific oyster Crassostrea gigas.
AB  - BACKGROUND: Shellfish is one of the most common food allergens. Despite the
      recent cloning and molecular identification of the major heat stable crustacean
      allergens in shrimp, lobster and crab, there have been no similar studies on
      molluscs to which a significant portion of populations allergic to shellfish are
      also hypersensitive. Recent biochemical evidence suggests that tropomyosin is
      also an allergen in molluscs, but data on the molecular cloning, nucleotide
      sequencing, expression and IgE binding to mollusc tropomyosin are lacking.
      OBJECTIVE: This study was undertaken to clone, identify and determine the primary
      structure of a major IgE-reactive mollusc allergen in oyster at the DNA and
      protein level. METHODS: We constructed an expression cDNA library from the
      Pacific oyster Crassostrea gigas. This library was screened for IgE binding
      clones using sera from 15 subjects with a well-documented history of type I
      hypersensitivity reactions to oysters. An IgE reactive clone was selected and sub
      cloned into plasmids for nucleotide sequence determination and expression in E.
      coli. RESULTS: We identified a 1.3-kb cDNA designated as Cra g 1.03. Expression
      of Cra g 1.03 in plasmid vector pGEX produced a 59-kDa recombinant fusion protein
      reactive to the IgE antibodies from patients with oyster allergies but not non
      allergic controls. Cra g 1.03 has an open reading frame of 233 amino acids and
      demonstrates marked similarity in amino acid composition and peptide sequence
      with mollusc and crustacean tropomyosins. Absorption of oyster allergic sera with
      Cra g 1.03 totally removed IgE reactivity to oyster extract. Moreover, absorption
      of allergic sera with recombinant shrimp tropomyosin (Met e 1), lobster
      tropomyosin (Pan s 1) and crab tropomyosin (Cha f 1) removed most of the IgE
      reactivity to Cra g 1.03. CONCLUSION: Cra g 1.03 is the first oyster allergen
      identified at the molecular level. Nucleotide and amino acid comparison shows
      that this protein is the oyster tropomyosin.

PMID- 11529899
TI  - Molecular cloning, expression and modelling of cat allergen, cystatin (Fel d 3),
      a cysteine protease inhibitor.
AB  - BACKGROUND: Cats are an important source of indoor allergens. However, only two
      cat allergens, Fel d 1 and albumin, have been cloned and sequenced. IgE
      antibodies to Fel d 1 and albumin do not fully account for IgE responses to cat
      and there is good immunochemical evidence that cats produce other allergens.
      OBJECTIVE: To identify and define the molecular structure of the other potential
      cat allergens. METHODS: A cat skin cDNA library was screened using pooled serum
      obtained from five asthmatic patients which contained high levels of IgE antibody
      to cat dander. Selected cDNA clones were screened by plaque immunoassay and one
      cDNA clone, encoding cystatin, was expressed in E. coli. The three dimensional
      structure of cat cystatin was modelled using the SWISS-MODEL computer program.
      RESULTS: Three positive cDNA clones (A, B and C) were identified, two of which
      were fully sequenced. Clones A and C encoded the same 98 amino acid residue
      sequence which showed 79% and 75% homology with bovine and human cystatin A,
      respectively. The cat cystatin sequence contained the conserved cysteine protease
      inhibitor signature and two of three lipocalin motifs. By plaque immunoassay, 60
      90% of cat allergic sera had IgE ab to the expressed cystatin clones. The
      cysteine protease inhibitor motif was also partially conserved in dog allergen
      sequences, Can f 1 and Can f 2, which are lipocalins. The recombinant protein was
      expressed in E. coli as an 11-kDa protein, corresponding to the predicted MW of
      cat cystatin. The three-dimensional structure of cat cystatin was modelled on
      human cystatin structures. CONCLUSION: A newly identified allergen, cystatin (Fel
      d 3), has been cloned from cat skin and is a member of the cysteine protease
      inhibitor family.

PMID- 11529901
TI  - Prevention of new sensitizations in monosensitized subjects submitted to specific
      immunotherapy or not. A retrospective study.
AB  - BACKGROUND: Specific immunotherapy is the only currently available allergen
      orientated treatment able to modify the natural history of respiratory allergic
      diseases. Safety and clinical efficacy of this treatment are well documented, but
      evidence about the ability to reduce new sensitizations is still poor. OBJECTIVE:
      We report a retrospective study conducted in order to assess the prevention of
      new sensitizations in monosensitized subjects treated with specific immunotherapy
      vs. monosensitized patients treated with anti-allergic drugs. METHODS: 8396
      monosensitized patients with respiratory symptoms were selected according to an
      open, retrospective design. Group A included 7182 patients submitted to specific
      immunotherapy (and anti-allergic drugs when needed) for 4 years and then treated
      with drugs for at least 3 years. Group B included 1214 patients treated only with
      drugs for at least 7 years. All patients underwent prick test with a standard
      panel of allergens and total and specific IgE determination before and after 4
      years of treatment and again 3 years later. RESULTS: Groups were well balanced.
      Polysensitized subjects were 23.75% in Group A and 68.03% in Group B after 4
      years (P < 0.0001) and 26.95% and 76.77%, respectively, after 7 years (P <
      0.0001). Asthmatic subjects were more prone to develop polysensitization in
      comparison to subjects suffering only from rhinitis (32.14% instead of 27.29%
      after 4 years, 36.5% instead of 31.33% after 7 years; P < 0.0001). Specific IgE
      decreased by 24.11% in Group A and increased by 23.87% in Group B (P < 0.0001).
      Total IgE decreased by 17.53% in Group A and increased by 13.71% in Group B (P <
      0.0001). CONCLUSIONS: Specific immunotherapy was observed retrospectively to
      reduce new sensitizations in monosensitized subjects suffering from respiratory
      allergic diseases.

PMID- 11529902
TI  - Venom immunotherapy induces monocyte activation.
AB  - BACKGROUND: Venom immunotherapy (VIT) is an efficient treatment of hymenoptera
      venom allergy. The mechanism of VIT is based on the induction of tolerance of
      allergen-specific Th2 cells. The mechanisms of this T cell modulation are
      unknown, and could depend on cytokines produced by other cell types such as
      interleukin (IL)-12, tumour necrosis factor (TNF)-alpha and IL-10 by monocytes.
      OBJECTIVE: To assess if VIT modifies the monocyte production of IL-12, TNF-alpha
      and IL-10 during the 45 first days of treatment. METHODS: Fourteen patients and
      seven controls were included. Blood samples were taken once in controls and at
      day (D)1, D30 and D45 of VIT in patients. Monocytes were isolated, cultured with
      and without lipopolysaccharide (LPS), and the culture supernatant was harvested.
      IL-10, IL-12 and TNF-alpha were assayed in supernatants by ELISA. RESULTS:
      Baseline cytokine levels were not statistically different between patients and
      controls. During treatment, an increase of spontaneous monocyte production of IL
      12 and TNF-alpha was observed at D15 and D45. The production of IL-10 increased
      at D15 and D45 but not significantly. After LPS-stimulation, IL-12, TNF-alpha and
      IL-10 monocyte production was not modified by VIT. CONCLUSION: VIT induces a
      monocyte activation characterized by a delayed overproduction of IL-12 and TNF
      alpha. These cytokines could be relevant to the inhibition of Th2 cells during
      VIT. Therefore, VIT-induced tolerance could depend not only on the specific
      action of venom antigens on T cells, but also on a secondary non-specific action
      of monocytes.

PMID- 11529903
TI  - Differential inhibition of inflammatory effector functions by petasin, isopetasin
      and neopetasin in human eosinophils.
AB  - BACKGROUND: Priming of eosinophils with granulocyte-macrophage colony-stimulating
      factor (GM-CSF) and subsequent stimulation with platelet-activating factor (PAF)
      or the anaphylatoxin C5a is associated with a rapid production of leukotrienes
      (LTs) and release of eosinophil cationic protein (ECP). OBJECTIVE: This study was
      designed to determine the effects of the sesquiterpene esters petasin, isopetasin
      and neopetasin on LT generation and ECP release in eosinophils in vitro. METHODS:
      The model of eosinophil activation described above was used to induce LT
      production and ECP release. Cells were incubated with petasins and control
      inhibitors prior to priming and stimulation. To analyse intracellular steps of
      eosinophil activation and determine potential drug targets, some key signalling
      events were studied. Activity of cytosolic phospholipase A2 (cPLA(2)) was
      measured by analysing the generation of arachidonic acid (AA). Translocation of 5
      lipoxygenase (5-LO) was observed using immunofluorescence microscopy.
      Intracellular calcium concentrations [Ca2+]i were measured by a bulk
      spectrofluorometric assay. RESULTS: Whereas all three compounds inhibited LT
      synthesis, ECP release from eosinophils was blocked by petasin only, but not
      isopetasin or neopetasin. Similarly, PAF- or C5a-induced increases in [Ca2+]i
      were completely abrogated by petasin only, whereas isopetasin and neopetasin had
      significant lower blocking efficacy. Moreover, only petasin, but not isopetasin
      or neopetasin, prevented increases in cPLA(2) activity and 5-LO translocation
      from the cytosolic compartment to the nucleus envelope in calcium ionophore
      stimulated eosinophils. CONCLUSION: These data suggest that different petasins
      may at least partially block different intracellular signalling molecules. To
      reduce LT synthesis, isopetasin and neopetasin may act at the level of or distal
      to 5-LO. In contrast, petasin may inhibit inflammatory effector functions in
      human eosinophils by disrupting signalling events at the level of or proximal to
      phospholipase Cbeta (PLCbeta), besides its potential inhibitory activity within
      mitogen-activated protein kinase (MAPK) and LT pathways.

PMID- 11529904
TI  - Mucosal output of eotaxin in allergic rhinitis and its attenuation by topical
      glucocorticosteroid treatment.
AB  - BACKGROUND: Eotaxin is a chemokine that attracts and activates eosinophils. The
      present study examines the occurrence of eotaxin in nasal mucosal surface liquids
      in patients with seasonal allergic rhinitis without allergen exposure and during
      repeat allergen challenge with and without topical glucocorticosteroid treatment.
      The number of subepithelial eosinophils and mucosal outputs of bulk plasma
      (alpha2-macroglobulin) and eosinophil cationic protein (ECP) are also examined.
      METHODS: Twelve patients underwent daily allergen challenges for 6 days.
      Separately, 14 patients, who were receiving budesonide and placebo in a parallel
      group design, also underwent allergen challenge for 6 days. Nasal biopsies were
      obtained before and 24 h after the allergen challenge series, and lavages were
      carried out before and 15 min after selected allergen challenges. RESULTS: At
      baseline nasal lavage fluid levels of eotaxin correlated to levels of alpha2
      macroglobulin and ECP. After the first allergen challenge there was a correlation
      between nasal lavage fluid levels of eotaxin and ECP. Repeat allergen exposure
      increased the mucosal output of eotaxin (P <0.05) and ECP (P <0.01) as well as
      eosinophil numbers (P <0.01), but no correlation was found between increased
      eosinophil numbers and eotaxin. Budesonide reduced eotaxin levels during repeat
      allergen challenge (P <0.05). CONCLUSIONS: Repeat allergen exposure in allergic
      rhinitis is associated with increased mucosal output of eotaxin. Topical
      budesonide attenuates this effect, suggesting the possibility that inhibitory
      effects on mucosal eotaxin may contribute to anti-eosinophilic actions of topical
      glucocorticosteroids.

PMID- 11529905
TI  - Freezing of homogenized sputum samples for intermittent storage.
AB  - BACKGROUND: Among the reasons that restrict the application of sputum induction
      in outpatient settings is the need for processing of samples within 2 h after
      induction. OBJECTIVE: The aim of our study was to assess whether freezing is
      suitable for intermediate storage of sputum samples before processing. METHODS:
      We compared differential cell counts between two sputum aliquots derived from the
      same sample. One aliquot was processed within 2 h after production and one, after
      it had been frozen under addition of dimethyl-sulfoxid (DMSO) and stored up to 10
      days at -20 degrees C. Thirty-five samples were frozen immediately prior to
      preparation of cytospins, and 10 samples were frozen at an even earlier stage,
      directly after homogenization. RESULTS: In both sets of experiments we observed a
      significant relationship between frozen and native samples regarding macrophages,
      neutrophils and eosinophils, as indicated by respective intraclass correlation
      coefficients of 0.96, 0.96, and 0.93 in the first, and of 0.92, 0.96 and 0.77 in
      the second experiments. CONCLUSION: Our results indicate that the freezing of
      sputum samples at different stages of processing does not alter sputum morphology
      to an extent that affects the results of differential cell counts.

PMID- 11529906
TI  - Proinflammatory cytokines (IL-17, IL-6, IL-18 and IL-12) and Th cytokines (IFN
      gamma, IL-4, IL-10 and IL-13) in patients with allergic asthma.
AB  - Allergen-reactive T helper type-2 (Th2) cells and proinflammatory cytokines have
      been suggested to play an important role in the induction and maintenance of the
      inflammatory cascade in allergic asthma. We compared the plasma concentrations of
      novel proinflammatory cytokines IL-17 and IL-18, other proinflammatory cytokines
      IL-6 and IL-12, Th2 cytokines IL-10 and IL-13, and intracellular interferon-gamma
      (IFN-gamma) and IL-4 in Th cells of 41 allergic asthmatics and 30 sex- and age
      matched health control subjects. Plasma cytokines were measured by enzyme-linked
      immunosorbent assay. Intracellular cytokines were quantified by flow cytometry.
      Plasma IL-18, IL-12, IL-10, IL-13 concentrations were significantly higher in
      allergic asthmatic patients than normal control subjects (IL-18: median 228.35
      versus 138.72 pg/ml, P < 0.001; IL-12: 0.00 versus 0.00 pg/ml, P = 0.001; IL-10:
      2.51 versus 0.05 pg/ml, P < 0.034; IL-13: 119.38 versus 17.89 pg/ml, P < 0.001).
      Allergic asthmatic patients showed higher plasma IL-17 and IL-6 concentrations
      than normal controls (22.40 versus 11.86 pg/ml and 3.42 versus 0.61 pg/ml,
      respectively), although the differences were not statistically significant (P =
      0.077 and 0.053, respectively). The percentage of IFN-gamma-producing Th cells
      was significantly higher in normal control subjects than asthmatic patients
      (23.46 versus 5.72%, P < 0.001) but the percentage of IL-4 producing Th cells did
      not differ (0.72 versus 0.79%, P > 0.05). Consequently, the Th1/Th2 cell ratio
      was significantly higher in normal subjects than asthmatic patients (29.6 versus
      8.38%, P < 0.001). We propose that allergic asthma is characterized by an
      elevation of both proinflammatory and Th2 cytokines. The significantly lower
      ratio of Th1/Th2 cells confirms a predominance of Th2 cells response in allergic
      asthma.

PMID- 11529907
TI  - Children with atopic dermatitis who carry toxin-positive Staphylococcus aureus
      strains have an expansion of blood CD5- B lymphocytes without an increase in
      disease severity.
AB  - Toxin-positive strains of Staphylococcus aureus (T + S. aureus) are present on
      the skin of some but not all patients with atopic dermatitis. Many staphylococcal
      toxins are superantigens, which can stimulate the immune response and thus may
      potentially lead to the very high levels of IgE characteristic of this condition,
      as well as exacerbating the clinical disease. The aim of this study was to
      determine whether the presence of T + S. aureus on the skin of children with
      atopic dermatitis was associated with in vivo evidence of a heightened humoral
      immune response, higher IgE levels and more severe clinical disease. Toxin gene
      expression in S. aureus isolated from the eczematous lesions of 28 children with
      atopic dermatitis was assessed by PCR. Clinical and immune data were also
      collected from this cohort. Thirteen of the 28 children (46%) were colonized with
      T + S. aureus strains. The presence of T + S. aureus was associated with a
      significant expansion in peripheral blood CD5- B cells (P = 0.01), and the more
      toxin types identified the greater the B-cell expansion (P = 0.002). However, in
      this cohort of children with atopic dermatitis, despite th in vivo expansion of B
      cells in children harbouring T + S. aureus, there was no associated increase in
      IgE levels or in clinical disease severity scores.

PMID- 11529909
TI  - Effects of granulocyte-macrophage colony stimulating factor (GM-CSF) in vivo on
      cytokine production and proliferation by spleen cells.
AB  - GM-CSF is a potent stimulator of haematopoietic cells as well as some functions
      of granulocytes and macrophages. GM-CSF has many clinical uses; however, little
      is known about the effects of GM-CSF treatment in vivo on the responses of tissue
      lymphocytes in terms of secretion of Th-1 and Th-2 cytokines. We investigated
      this issue by measuring the responses of spleen cells from mice 24 h after
      treatment i.p. with saline or rmGM-CSF. GM-CSF at 16.7-50.0 microg/kg
      significantly increased (P < 0.01) spleen cellularity 2-2.5-fold and enhanced
      proliferative responses of non-stimulated (no mitogen) as well as concanavalin A
      (Con A)-stimulated spleen cells. Secretion of IFN-gamma by Con A (2.5 microg/ml)
      stimulated spleen cells was significantly (P < 0.01) increased from 1.8 microg/ml
      by control spleen cells to 5.2 microg/ml by GM-CSF spleen cells. IL-10 production
      was greater (0.25 microg/ml, P < 0.05) by Con A-stimulated spleen cells from GM
      CSF-treated mice compared to control spleen cells (0.06 microg/ml). By contrast,
      there were no significant differences in IL-4 production by Con A-stimulated
      spleen cells from the different groups. These results show that GM-CSF treatment
      increases spleen cellularity and primes lymphocytes for enhanced responses. The
      enhanced production of Th-1 cytokines by primed lymphocytes may partially explain
      the beneficial role of in vivo administration of GM-CSF in several clinical
      situations.

PMID- 11529908
TI  - Deregulated cytokine network and defective Th1 immune response in multiple
      myeloma.
AB  - Intracellular cytokine production by peripheral blood mononuclear cells (PBMC)
      was analysed in 51 patients with multiple myeloma (MM), 22 with monoclonal
      gammopathy of undetermined significance (MGUS) and 20 healthy subjects, as a
      parameter of immunological dysfunction in MM. An increased proportion of T cells
      and HLA-DR+ cells producing IL-6 was observed in MM patients with active disease
      (at diagnosis and relapsing) compared with patients in remission and with MGUS,
      whereas no difference of IFN-gamma+, IL-2+ PBMC between patients and controls was
      evident. Determination of serum cytokine levels demonstrated that the imbalanced
      IL-6 production by T cells and the defective anti-tumour Th1 cell activity were
      related to elevated levels of IL-6 and IL-12. In vitro studies of PHA- and anti
      CD3/anti-CD28 MoAbs stimulation of PBMC demonstrated the ability of lymphocytes
      from MM patients to differentiate towards the Th1 subset in the presence of rIL
      12. By contrast, addition of exogenous rIL-6 impaired IFN-gamma production by rIL
      12-prompted T cells. Inhibition of Th1 polarization of the immune response by IL
      6 was direct on T cells and not mediated by dendritic cells (DC). Evaluation of
      the ability of MM-derived DC to stimulate cell proliferation of allogenic T
      lymphocytes and produce IL-12 in vitro, in fact, suggested that MM-derived DC
      were functionally active. Taken as a whole, these results indicate that a
      deregulated cytokine network occurs in active MM. They also suggest that
      increased IL-6 production by peripheral T lymphocytes contributes to the immune
      dysfunction observed in MM, and enables tumour cells to escape immune
      surveillance by preventing the anti-tumour Th1 immune response.

PMID- 11529911
TI  - Antiphosphatidylserine antibodies are elevated in normal tension glaucoma.
AB  - The two main entities of open-angle glaucoma are primary open-angle glaucoma
      (POAG) and normal tension glaucoma (NTG). Both diseases may be associated with
      autoimmune processes. Therefore, IgG and IgM antibodies to phospholipids (APL)
      and their subspecies cardiolipin (ACL), phosphatidylserine (APS) and beta2
      glycoprotein (beta2GP) were determined in 43 NTG patients, 40 POAG patients and
      40 healthy controls in a prospective study. The most prominent observation was
      the increase in APS concentrations in NTG patients (IgG 20.6 +/- 2.7 U/ml, IgM
      24.4 +/- 3.4 U/ml) compared with POAG patients (IgG 8.8 +/- 1.2 U/ml, IgM 11.0 +/
      1.7), and controls (IgG 7.7 +/- 1.3 U/ml, IgM 12.8 +/- 1.5 U/ml). APS may be
      important due to their binding specificity to phosphatidylserine molecules which
      become accessible during apoptosis; this in turn may lead to local thrombosis.

PMID- 11529910
TI  - Analysis of mercury-induced immune activation in nonobese diabetic (NOD) mice.
AB  - In susceptible mice, the heavy metal ion mercury is able to induce a strong
      immune activation, which resembles a T helper 2 (Th2) type of immune response and
      is characterized by a polyclonal B cell activation, formation of high levels of
      IgG1 and IgE antibodies, production of autoantibodies of different specificities
      and development of renal IgG deposits. In the present study, we analysed the in
      vivo effects of mercury in nonobese diabetic (NOD) mice, which is believed to
      develop a spontaneous Th1 cell-mediated autoimmune diabetes similar to type 1
      diabetes in humans. Three weeks of treatment with mercury induced a strong Th2
      like immune/autoimmune response in NOD mice. This response was characterized by
      an intensive increase in splenic IgG1 antibody secreting cells, a marked
      elevation in serum IgE levels, a substantial increase in splenic IL-4 mRNA, but a
      significant decrease in splenic IFN-gamma mRNA. Mercury-induced IgG1 antibodies
      were mainly against ssDNA, TNP and thyroglobulin, but not against nucleolar
      antigen. Moreover, mercury-injected NOD mice developed high titres of IgG1
      deposits in the kidney glomeruli. We further tested if the generated Th2 response
      could interfere with the development of insulitis and diabetes in NOD mice. We
      found that three weeks of treatment with mercury was also able to significantly
      suppress the development of insulitis and postpone the onset of diabetes in these
      mice. Thus, mercury-induced immune activation can counter-regulate the Th1 cell
      mediated autoimmune responses and confer a partial protection against autoimmune
      diabetes in NOD mice.

PMID- 11529912
TI  - Autoantibodies from patients with coeliac disease recognize distinct functional
      domains of the autoantigen tissue transglutaminase.
AB  - The enzyme tissue transglutaminase (tTG) has been recently identified to
      represent a highly sensitive and specific target of autoantibodies in coeliac
      disease. To characterize autoantigenic epitopes, we generated novel tTG deletion
      mutants by polymerase chain reaction, produced radiolabelled fragments by in
      vitro transcription/translation, immunoprecipitated the mutants using sera from
      patients with coeliac disease, and related the binding data with putative
      structural and functional domains of human tTG. We show that tTG antibody
      positive sera display a heterogeneous autoantibody response covering distinct
      regions of the molecule. The N-terminal and C-terminal third of tTG, comprising
      amino acid (aa) 1-281 and aa 473-687, harbour the dominant epitopes (67.4% and
      69.4% positive), whereas the catalytic region is of minor antigenicity (22.5%
      positive). Autoantibodies directed to one, two and three domains were observed in
      36.7%, 28.6% and 22.4% of patients, respectively. Comparative analysis revealed
      the presence of strictly conformational epitopes which were dependent on the N
      terminus (aa 1-12) or the intact beta-barrel domains in the C-terminus (aa 473
      497, aa 649-687). In conclusion, we here demonstrate for the first time that the
      humoral autoimmunity is directed against distinct functional tTG domains. The
      spectrum of autoantibodies indicates that the native folded protein may be the
      target of autoantibodies.

PMID- 11529913
TI  - Differential responsiveness of cord and adult blood monocytes to hepatocyte
      growth factor.
AB  - Monocytes as antigen-presenting cells play an important role in host defence.
      There are several cytokines affecting monocyte function. We demonstrate that both
      adult and cord blood monocytes constitutively express hepatocyte growth factor
      (HGF) receptor, MET. HGF significantly down-regulated MET expression of adult
      blood monocytes, compared with cord blood monocytes, when cultured either in RPMI
      1640 containing 10% FBS or serum-free medium. Surface levels of MET correlated
      with c-met mRNA levels both in adult and cord blood when cultured. MET expression
      was down-regulated by treating with actinomycin D or cycloheximide. HGF
      stimulated DNA synthesis of adult monocytes, but not cord blood. HGF enhanced
      antigen-presenting capacity of adult blood monocytes but not cord blood
      monocytes. HGF up-regulated HLA class I expression in adult monocytes but not in
      cord blood monocytes. The current results suggest that the failure of cord blood
      monocytes to respond to HGF may be responsible, in large part, for their
      functional immaturity.

PMID- 11529914
TI  - NF-kappaB is involved in the regulation of CD154 (CD40 ligand) expression in
      primary human T cells.
AB  - Cognate interactions between CD154 (CD40 ligand, CD40L) on activated T cells and
      its receptor CD40 on various antigen-presenting cells are involved in thymus
      dependent humoral immune responses and multiple other cell-mediated immune
      responses. We have studied the regulation of CD154 expression in human T cells
      after activation with anti-CD3 and anti-CD28 antibodies or after pharmacological
      activation of protein kinase C with phorbol 12-myristate 13-acetate, and the
      calcium ionophore ionomycin. Under these conditions, transcription of the CD154
      gene was rapidly induced without requiring de novo protein synthesis.
      Pharmacological inhibitors of NF-kappaB activation down-regulated CD154 mRNA and
      protein levels. Cyclosporin A, an inhibitor of NF-AT activation, acted similarly,
      and the effects of both inhibitors were additive. A potential NF-kappaB binding
      site is present within the CD154 promoter at positions -1190 to - 1181. In
      electrophoretic mobility shift assays, this sequence was specifically bound by NF
      kappaB present in nuclear extracts from activated T cells. Furthermore, in
      transient co-transfection of Jurkat T cells, p65 activated the transcription of a
      reporter construct containing a multimer of this NF-kappaB binding site. These
      observations demonstrate a role of NF-kappaB transcription factors in the
      regulation of CD40L expression in activated primary human T cells.

PMID- 11529915
TI  - In vitro generation of human CD86+ dendritic cells from CD34+ haematopoietic
      progenitors by PMA and in serum-free medium.
AB  - The cytokine requirements to differentiate CD34+ progenitor cells from different
      origins either cord blood (CB) or peripheral blood (PB) into dendritic cells (DC)
      are known to be different. In addition to DC, macrophages and neutrophils are
      generated. On the other hand, phorbol esters such as PMA induce primary human
      CD34+ bone marrow (BM) progenitor cells to differentiate into functional DC and
      no other lineages are generated. In addition, FCS is used as culture supplement
      in most of the protocols described which contains additional foreign antigens
      potentially skewing the resulting immune response. Therefore, we evaluated the
      ability to differentiate CB- and PB-CD34+ progenitor cells into DC with PMA and
      under serum-free conditions. In this study, we delineate the maturation of
      cultured human blood DC by analysis of expression co-stimulatory molecule B7-2
      (CD86). Human mature DC with typical morphology and surface antigen phenotype
      (CD1a-, CD83+ and CD86+) were obtained from CB- and PB-CD34+ progenitor cells
      after 1 week of culture in serum-free medium upon stimulation with PMA alone. The
      same result was obtained from ex vivo-expanded BM-CD34+ cells. CD86+ yield was
      increased by PMA compared to cytokine cocktails (28.0% +/- 7.0 versus 15.3% +/-
      5.6 for CB and 44.6% +/- 7.5 versus 28.1% +/- 7.5 for PB, respectively). CD86 was
      most up-regulated in the presence of the calcium ionophore ionomycin. However,
      the number of viable cells after differentiation was decreased by PMA plus
      ionomycin (P < 0.05) or plus TNF-alpha (P > 0.05) as compared with that in PMA
      alone. We conclude that PMA is a potent activator to differentiate human CD34+
      cells into mature DC in serum-free medium. This may be used for in vitro studies
      of primed or genetically modified DC against infectious and tumour-associated
      antigens.

PMID- 11529916
TI  - HLA-A and HLA-B transcription decrease with ageing in peripheral blood
      leucocytes.
AB  - Immunosenescence involves modifications of humoral and cellular immunity. In a
      previous study, we have shown a locus-dependent reduction of HLA class-I cell
      surface expression on peripheral lymphocytes and monocytes with advancing age.
      Here we report the quantitative analysis of HLA-A and -B transcripts from PBL of
      54 healthy subjects aged 21-90 years. Using a competitive RT-PCR method, we
      observed a significant decrease of HLA-A (P < 0.0001) and -B (P = 0.0025) mRNA
      contents with increasing age. Secondly, to investigate this locus-dependent
      alteration of HLA class-I transcription, we performed EMSA using nuclear extracts
      from PBL of five young (24-31-year-old) and 5 elderly (58-69 years old) donors
      with locus A and B sequences of the Enh-A as probes. No qualitative variation of
      EMSA profiles appeared between the two groups of donors with 6 and 4 bandshift
      for the locus A and B, respectively. Quantitatively, we observed a significant
      increase of B4 intensity in the elderly group compared to the young group (P <
      0.05). These results suggest that the variation of DNA binding protein could
      contribute to the lower transcription of HLA-A and -B with ageing. These
      alterations of HLA class-I expression at the transcriptional level could lead to
      the unresponsiveness of CD8 T cells due to default of antigen presentation with
      ageing.

PMID- 11529917
TI  - Immune complexes (IC) down-regulate the basal and interferon-gamma-induced
      expression of MHC class II on human monocytes.
AB  - The interaction of Fc receptors for IgG (FcgammaRs) on monocytes/macrophages with
      immune complexes (IC) triggers regulatory and effector functions. Previous
      studies have shown that FcgammaR-IC interactions inhibit the IFN-gamma-induced
      expression of MHC class II in murine macrophages. However, the mechanism(s)
      responsible for these effects have not been elucidated. In addition, whether this
      IC-dependent effect also occurs in human cells is not known. Taking into account
      the fact that IC and IFN-gamma are frequently found in infections and autoimmune
      disorders, together with the crucial role MHC class II molecules play in the
      regulation of immune response, we explored the effect and mechanism of IC-induced
      MHC class II down-regulation in human peripheral blood mononuclear cells (PBMC).
      This effect was studied either in the presence or absence of IFN-gamma. We
      demonstrate that IC exert a drastic inhibition of basal and IFN-gamma-induced
      expression of MHC class II on human monocytes. This effect was mediated through
      the interaction of IC with both FcgammaRI and FcgammaRII. Moreover, similar
      results were obtained using supernatants from IC-treated PBMC. The IC-induced
      down-regulation of MHC class II is abrogated by pepstatin and phosphoramidon,
      supporting the role of aspartic protease(s) and metalloprotease(s) in this
      process. In parallel with MHC class II expression, antigen presentation was
      markedly inhibited in the presence of IC.

PMID- 11529918
TI  - Increased distribution and expression of CD64 on blood polymorphonuclear cells
      from patients with the systemic inflammatory response syndrome (SIRS).
AB  - Evidence is growing to suggest that the multiple organ damage of the systemic
      inflammatory response syndrome (SIRS) arises from the untoward activity of blood
      polymorphonuclear cells (PMNs), which upon activation acquire the IgG high
      affinity receptor, CD64. In the current study, flow cytometry was used to assess
      the prevalence of CD64-bearing PMNs and the intensity of expression of CD64 in
      whole blood samples from 32 SIRS patients, 11 healthy normal subjects and from
      eight non-SIRS patients in the intensive care unit (ICU). The percentage of PMNs
      expressing CD64 was higher in SIRS patients (mean 65%) than in non-SIRS patients
      (mean 42%; P < 0.02) and in healthy controls (mean 19%; P < 0.001) and was
      particularly evident in patients with SIRS and sepsis (mean 71%; P < 0.02) as
      opposed to SIRS alone (mean 55%). There were more CD64 molecules expressed on
      PMNs from patients with SIRS (median 1331 molecules/cell) in comparison with PMNs
      from healthy subjects (median 678 molecules/cell; P < 0.01). The highest
      intensity of CD64 expression was associated with PMNs from patients with both
      SIRS and sepsis. Functional studies revealed that the supranormal binding of PMNs
      from patients with SIRS to endothelial monolayers treated with TNFalpha was
      impeded by anti-CD64 antibodies (mean 24% inhibition; P < 0.01). Monitoring the
      distribution of CD64+ PMNs and their level of CD64 expression could be of
      assistance in the rapid discrimination of patients with SIRS from other ICU
      patients and in the identification of PMNs which are likely to participate in the
      pathological manifestations of the disease.

PMID- 11529919
TI  - Naive and memory CD4+ T cells and T cell activation markers in HIV-1 infected
      children on HAART.
AB  - The objective of this study was to investigate the relationship between
      peripheral blood CD4+ T cell subsets and routine viro-immunological markers in
      vertically HIV-1-infected children undergoing highly active antiretroviral
      therapy (HAART). CD4+ and CD8+ T cell subsets were examined by three-colour flow
      cytometry. Plasma viraemia was quantified by a standardized molecular assay. A
      negative correlation between the %CD4+ T cells and both viral load and the %CD8+
      T cells was observed. A strong positive correlation between the %CD4 T cells and
      naive, CD38+ and non-activated CD4+ T cell subsets was found, whereas the %CD4 T
      cells correlated negatively with the numbers of memory, activated and memory
      activated CD4+ T cell subsets. Elevated percentages of CD8 T cells were
      associated with increased memory and CD4+ CD62L-T cell subsets, whereas the naive
      and CD4+ HLA-DRCD38+ subsets negatively correlated with the CD8%. Co-expression
      of CD62L on memory CD4+ cells and high expression of HLA-DR (but not of CD38)
      were associated with high viral load. No association between viral load and naive
      CD4+ T cells was observed. Specific CD4+ T cell subsets may be more informative
      than routine surrogate markers in defining the evolution of HIV infection and
      immune reconstitution in children.

PMID- 11529920
TI  - Molecular studies and NK cell function of a new case of TAP2 homozygous human
      deficiency.
AB  - In this paper we describe the clinical and molecular features of a new case (GOR)
      of homozygous human TAP2 deficiency, analysing the phenotype and function of NK
      cells. The patient presented from infancy with recurrent sinopulmonary
      infections; a selective IgG2 deficiency, negative antibody response to
      polysaccharide vaccination and low level of cell surface expression of HLA class
      I antigens were found. The sequence of TAP2 gene identified a single mutation, a
      C to T substitution changing the CGA arg codon at amino acid 220 into TGA stop
      codon in exon 3. By using MoAbs for KIRs, CD94, CD94/NKG2A and ILT2 we observed,
      in agreement with others, that the latter two receptors were overexpressed on
      TAP2-deficient NK cells. The inhibitory CD94/NKG2A and triggering CD94/NKG2C NK
      receptors, specific for HLA-E, appeared to be functional in a limited number of
      NK clones that could be expanded in vitro. Expression of HLA-E was virtually
      undetectable in GOR B-LCL and very faint in PBMC, further supporting that
      interactions of class I leader sequence nonamers with HLA-E in the ER depend on a
      functional TAP complex.

PMID- 11529921
TI  - A thiol proteinase inhibitor, E-64-d, corrects the abnormalities in concanavalin
      A cap formation and the lysosomal enzyme activity in leucocytes from patients
      with Chediak-Higashi syndrome by reversing the down-regulated protein kinase C
      activity.
AB  - We have reported previously that the abnormally down-regulated protein kinase C
      (PKC) causes cellular dysfunction observed in natural killer (NK) cells,
      polymorphonuclear leucocytes (PMNs) and fibroblasts from beige mouse, an animal
      model of Chediak-Higashi syndrome (CHS). Here we show that the abnormal down
      regulation of PKC activity also occurs in Epstein-Barr (EB) virus-transformed
      cell lines from CHS patients. When CHS cell lines were stimulated with
      concanavalin A (Con A) for 20 min, the membrane-bound PKC activity declined
      markedly, whereas that in control cell lines increased. We found that E-64-d,
      which protects PKC from calpain-mediated proteolysis, reversed the declined PKC
      activity and corrected the increased Con A cap formation to almost normal levels
      in CHS cell lines. We confirmed that the dysregulation of PKC activity also
      occurred in peripheral blood mononuclear leucocytes (PBMC) from CHS patients and
      that E-64-d corrected both the declined PKC activity and increased Con A cap
      formation. E-64-d also corrected the reduced lysosomal elastase and cathepsin G
      activity in CHS cell lines. In contrast, chelerythrin, a specific inhibitor of
      PKC, and C2-ceramide, which promotes PKC breakdown induced by calpain, increased
      Con A cap formation and inhibited both elastase and cathepsin G activity in
      normal cell lines. Moreover, we found that ceramide production in CHS cell lines
      increased significantly after Con A stimulation, which coincides with our
      previous observation in fibroblasts from CHS mice. These results suggest an
      association between ceramide-induced PKC down-regulation and the cellular
      dysfunctions in CHS.

PMID- 11529922
TI  - Anti-cytokeratin antibodies in sera of the patients with autoimmune hepatitis.
AB  - Antibodies to cytokeratin (CK) are found in some patients with autoimmune
      hepatitis (AIH). We hypothesized that serum antibodies to CK8, CK18 and CK19 may
      be formed in patients with AIH. We established an enzyme-linked immunosorbent
      assay (ELISA) to quantify anti-CK8, anti-CK18 and anti-CK19 antibodies in sera of
      patients with AIH. In addition, we quantified circulating CK8:anti-CK8 antibody
      as well as CK18:anti-CK18 antibody immune complexes in patients' sera, by an
      enzyme-linked immunosorbent assay (ELISA). Furthermore, to evaluate the
      expression of CK8, CK18 and CK19 in liver tissue, immunohistochemical stainings
      were performed. Significantly high levels of anti-CK8, anti-CK18 and anti-CK19
      antibodies were demonstrated in patients with AIH compared with normal volunteers
      and patients with chronic active hepatitis C (CH-C). In addition, these
      antibodies were significantly decreased after steroid treatment. Levels of
      CK8:anti-CK8 and CK18:anti-CK18 immune complexes in sera of patients with AIH
      were significantly high compared with those of patients with CH-C and normal
      volunteers. Immunohistochemically, CK8 or CK18 were absent from some hepatocytes
      of AIH. CK19 was aberrantly expressed in periportal hepatocytes in patients with
      AIH, but not CH-C. This is the first study to quantify anti-CK8, anti-CK18, anti
      CK19 antibodies and immune complexes in patients with AIH. The clinical
      significance of anti-CK antibodies and their immune complexes of AIH is also
      discussed.

PMID- 11529923
TI  - Bone marrow-derived dendritic cells from experimental allergic encephalomyelitis
      induce immune tolerance to EAE in Lewis rats.
AB  - We have previously shown that dendritic cells (DC), upon being pulsed in vitro
      with encephalitogenic myelin basic protein peptide 68-86 (MBP 68-86) and injected
      subcutaneously (s.c.) back to healthy Lewis rats, transfer immune tolerance to
      experimental allergic encephalomyelitis (EAE) induced by immunization with MBP 68
      86 and Freund's complete adjuvant (FCA). We here assumed that DC become pulsed in
      EAE rats, and that expansion in vitro of such 'in vivo pulsed EAE-DC' might also
      have the capacity to induce immune tolerance to EAE, thereby eliminating the need
      for in vitro pulsing of DC with autoantigens which are still unknown in many
      autoimmune diseases in the human. In the present study, EAE-DC were generated
      from bone marrow of Lewis rats, with EAE induced with MBP 68-86 + FCA, and
      expanded in vitro by culture with GM-CSF and IL-4. In comparison with DC from
      normal rats, EAE-DC exhibited higher viability in the absence of growth factors,
      and presented specific antigen to naive T cells in vitro. The DC derived from
      both EAE and healthy rats stimulated strong proliferation in an antigen
      independent manner, lasting for 4 weeks after DC were s.c. injected into healthy
      rats. During this time, injection of EAE-DC did not induce clinical EAE. However,
      when these rats were immunized with MBP 68-86 + FCA, subsequent EAE was
      dramatically suppressed, and was associated with increased IFN-gamma expression,
      nitric oxide production, gradually reduced proliferation and cell apoptosis,
      compared with PBS-injected control EAE rats. LPS-treated DC did not induce
      tolerance, suggesting that the tolerance is mediated by an immature stage of DC.
      These observations support the hypothesis that EAE-DC can transfer immune
      tolerance to EAE, thereby omitting the step of characterizing specific
      autoantigen. Omitting the step of loading DC with antigen not only eliminates the
      extremely complex procedure of defining pathogenically-relevant autoantigens, but
      also avoids the risk of inducing immunogenicity of DC in the treatment of
      autoimmune diseases.

PMID- 11529924
TI  - Circulating gamma/delta T lymphocytes from systemic sclerosis (SSc) patients
      display a T helper (Th) 1 polarization.
AB  - Systemic sclerosis (SSc) is a connective tissue disease in which immune system
      activation is evidenced by high levels of different cytokines in the sera and/or
      in the supernatants of cultured peripheral blood mononuclear cells (PBMC) and by
      the presence of specific autoantibodies. gamma/delta T cells accumulate in the
      lung and the skin of SSc patients suggesting their potential role in the
      development and maintenance of the disease. The aim of this study was to assess
      cytokine production and cytotoxic activity of circulating gamma/delta T
      lymphocytes obtained from SSc patients and to evaluate their potential role
      during this disorder. Our results showed that both the proportion and the
      absolute number of IFN-gamma gamma/delta-producing cells (i.e. displaying a Th1
      polarization) in SSc was significantly higher than either the proportion and the
      absolute number of IL-4 gamma/delta-producing cells in SSc or the proportion and
      the absolute number of IFN-gamma gamma/delta-producing cells in healthy controls
      (P < 0.05 for both groups). Furthermore, the cytotoxic activity of enriched
      gamma/delta T cells was significantly increased in SSc patients compared with
      controls. The results concerning the Vdelta1+ T cell subset paralleled those of
      total gamma/delta T lymphocytes. In contrast, alpha/beta T cells from SSc and
      control subjects displayed Th2 cytokine production. All these findings were
      independent of both disease subset and clinical status. Our data demonstrate
      that, although SSc is generally considered a Th2 autoimmune disease, Th1
      polarization of gamma/delta T cells and an increase in their cytotoxic activity
      is observed in SSc, suggesting that gamma/delta T cells could have a relatively
      autonomous role in the pathogenesis in this disease.

PMID- 11529925
TI  - Occurrence of C-reactive protein in cryoglobulins.
AB  - A previous case report described the formation of a complex between a monoclonal
      IgA with cryolabile properties and C-reactive protein (CRP). Our study provides
      the first evidence for the frequent occurrence of CRP in cryoglobulins (Cg) of
      all three types according to Brouet's classification. We performed a systematic
      immunochemical analysis of cryoglobulins from 18 patients by Western blotting and
      in 15 of 18 cryoprecipitates a single band (23 KD), immunoreactive with anti-CRP
      antibody, was demonstrable irrespective of the clonal composition of the
      cryoglobulins. This band was detectable in 4/5 of type I, in 6/8 of type II, and
      in 5/5 of type III cryoprecipitates, classified according to Brouet et al. In
      addition, the complement proteins C1q and C3 were present in nearly all CRP
      containing cryoglobulins, presumably reflecting previous activation of the
      classical complement pathway at least. All three CRP-negative cryoprecipitates
      were derived from sera with low cryoglobulin content (1-2 g/l). Longitudinal
      investigation of 23 cryoprecipitates from seven patients confirmed that
      successful detection of CRP by Western blotting depends on the protein
      concentration of the cryoglobulins. Since complexed CRP was previously shown to
      be an effective activator of complement, via C1q binding, CRP may modulate
      pathophysiologic effects mediated by cryoglobulins in vivo.

PMID- 11529926
TI  - Amphipathic variable region heavy chain peptides derived from monoclonal human
      Wegener's anti-PR3 antibodies stimulate lymphocytes from patients with Wegener's
      granulomatosis and microscopic polyangiitis.
AB  - Amphipathic variable-region heavy chain 11-mer peptides from monoclonal human IgM
      antiproteinase-3 antibodies were studied for peripheral blood lymphocyte
      stimulation in 21 patients with Wegener's granulomatosis (WG) or microscopic
      polyangiitis (MPA), connective tissue disease controls and normal control
      subjects. Positive T-cell activation was observed in most experiments with WG
      patients' lymphocytes using amphipathic VH-region peptides from four different
      human monoclonal anti-PR3 antibodies. Control peptides of the same length but
      without amphipathic characteristics along with other amphipathic peptides not
      derived from monoclonal anti-PR3 sequence were employed as controls. No
      significant lymphocyte stimulation was observed with normal controls, but
      positive stimulation with amphipathic VH peptides was also recorded in other
      connective tissue disease controls mainly patients with rheumatoid arthritis.
      Amphipathic peptides not derived from anti-PR3 sequence did not stimulate WG
      lymphocytes. Our findings indicate that lymphocyte reactivity as an element of
      cell-mediated immunity may be activated by amphipathic VH-region amino acid
      sequences of autoantibodies which are themselves associated with diseases such as
      WG.

PMID- 11529927
TI  - Th2 dominance in nasal mucosa in patients with Wegener's granulomatosis.
AB  - Wegener's granulomatosis initially affects upper respiratory tract organs
      including the nasal mucosa in more than 90% of patients. The inflammation is
      typically granulomatous with associated vasculitis. T lymphocytes are usually a
      prominent component of the leucocyte infiltrate. Previous studies using
      peripheral blood T cells have implicated IFN-gamma rich Th1-type responses. This
      study addressed the cytokine milieu in nasal mucosa from 10 patients with active
      Wegener's granulomatosis using immunohistochemistry. Increased levels of CD3+ T
      cells and eosinophils were present compared with normal and disease controls.
      There was increased expression of IL-4, down-regulation of IL-2 and no detectable
      IFN-gamma. There was increased expression of the chemokine receptor CCR3 by
      infiltrating cells, consistent with an IL-4 dominant, Th2-biased response. In
      contrast, renal biopsy tissue from 10 patients with active Wegener's
      granulomatosis showed expression of IL-2 and IL-4. The Th2-type environment
      within nasal mucosa, often the initial site of disease activity in Wegener's, is
      consistent with a local allergic response in these patients.

PMID- 11529928
TI  - Elevated serum levels of matrix metalloproteinase-9 (MMP-9) in Kawasaki disease.
AB  - Matrix metalloproteinases (MMPs) play an important role in the progression of
      tumour cells and the invasion of inflammatory cells by degrading the
      extracellular matrix. In the MMP family, MMP-9 gelatinase is thought to
      contribute to the pathogenesis of inflammatory arteritis by disrupting the
      elastic lamina. The aim of the present study is to investigate the potential role
      of MMP-9 in Kawasaki disease (KD), an acute type of systemic vasculitis in
      children. We studied the total levels of MMP-9 (free proMMP-9 and free MMP-9) in
      the sera using a new assay system and the expression of MMP-9 mRNA in the
      leucocytes using reverse transcription-polymerase chain reaction in 18 patients
      with KD, 10 patients with sepsis and 10 healthy children (HC). The serum MMP-9
      levels were significantly higher (P < 0.01) in the acute phase of KD than in the
      acute phase of sepsis and HC. In the time course of KD, the serum MMP-9 levels
      decreased significantly (P < 0.01) from the subacute through the convalescent
      phases. In the acute phase of KD, the serum MMP-9 levels showed a significantly
      positive correlation (P < 0.05) with the circulating leucocyte counts, especially
      the neutrophil counts. Furthermore, the expression of MMP-9 mRNA in the
      circulating leucocytes increased in the acute phase of KD and decreased from the
      subacute through the convalescent phases. These findings indicate that an
      excessive amount of MMP-9 is present in the plasma during the acute phase of KD,
      thus suggesting that circulating leucocytes may be a source of the MMP-9 secreted
      into the circulation.

PMID- 11529929
TI  - CD antigens 2001.

PMID- 11529930
TI  - The genetic and immunopathological processes underlying collagen-induced
      arthritis.
AB  - Animal models of rheumatoid arthritis (RA) have provided substantial insights
      into basic pathogenic mechanisms of chronic inflammatory arthritis and autoimmune
      disease in general. Of the variety of models reported, collagen-induced arthritis
      (CIA) has been the most characterized in terms of both its pathogenesis and its
      underlying immunological basis. Collagen-induced arthritis has also been the
      model of choice in terms of testing potential new therapeutic agents for the
      treatment of human RA. Nevertheless, the complex nature of the balance between T
      cell cytokines and the chronic inflammatory processes is only recently becoming
      clear. This review focuses on these developments, highlighting their implications
      for our understanding of RA and for the use of CIA as a suitable animal model.

PMID- 11529931
TI  - Imaging T-cell antigen recognition and comparing immunological and neuronal
      synapses.

PMID- 11529932
TI  - The regulation of FasL expression during activation-induced cell death (AICD).
AB  - Activation-induced cell death (AICD), a Fas ligand (FasL)-dependent pathway, is
      important for maintaining T-cell homeostasis. Interleukin-2 (IL-2), an enhancer
      of AICD, can also enhance FasL expression. However, we show that the level of
      FasL or FLIP protein did not correlate with the susceptibility to AICD. Some T
      cells expressed high levels of FasL yet failed to undergo AICD, while others
      expressed little FasL and were sensitive. AICD susceptibility did not correlate
      with the kinetics of FasL up-regulation or down-regulation. The down-regulation
      of FasL can be mediated by a metalloprotease. However, we describe an alternative
      mechanism for the loss of FasL by endocytosis. Endocytosis inhibitors such as
      cytochalasins, sodium azide, deoxyglucose, or low temperatures prevented the loss
      of FasL. KB8301, a metalloprotease inhibitor had no effect on the loss of FasL or
      AICD in the T cells. Enhancing FasL expression was not crucial for AICD and the
      down-regulation of FasL proceeded via endocytosis.

PMID- 11529933
TI  - Apoptosis and peripheral blood lymphocyte depletion in coeliac disease.
AB  - In coeliac disease (CD) immunological abnormalities are not confined to the small
      bowel and it has been suggested that changes in peripheral blood lymphocytes
      (PBL), such as lymphopenia and increased T-cell activation, may predispose to
      malignant or autoimmune complications of this condition. In the light of the
      recent findings about the Fas-Fas ligand (FasL) system in regulating lymphocyte
      homeostasis, the aim of the present study was to investigate peripheral
      lymphocyte Fas-mediated apoptosis in CD to establish whether the homeostatic role
      of apoptosis in peripheral T-cell selection is maintained. Moreover, because a
      soluble form of Fas has been described to be functionally implicated in the Fas
      signalling system, suggesting a relationship between some disorders and soluble
      Fas function, we measured levels of soluble Fas in sera of coeliac patients and
      analysed the relationship between these levels and the proportions of apoptotic
      and Fas(+) PBL to further explore the function of the Fas-FasL pathway in this
      condition. Finally, we evaluated whether the increased prevalence of
      anticardiolipin antibodies, recently described in CD, could be related to PBL
      apoptosis in this condition. We demonstrated an increased apoptosis and higher
      levels of Fas and FasL expression in PBL isolated from untreated coeliac patients
      when compared to treated coeliac patients and controls. In addition, low levels
      of soluble Fas and a significant positive correlation between anticardiolipin
      antibodies and PBL apoptosis were found in untreated CD. Then, our results showed
      an increased susceptibility of PBL to undergo Fas-mediated apoptosis in active
      CD. This increased apoptosis could be responsible for both lymphopenia and
      immunogenic exposure of phospholipids with subsequent production of
      autoantibodies.

PMID- 11529934
TI  - Intraspecies heterogeneity of immunoglobulin alpha-chain constant region genes in
      rhesus macaques.
AB  - Immunoglobulin A (IgA) is the major antibody class present in external secretions
      and is also an important component of serum immunoglobulins. On mucosal surfaces,
      IgA represents a first line of defence by neutralizing invading pathogens. The
      number of IgA constant-region genes (C alpha) present in different mammalian
      species is variable. Immunoglobulin C alpha genes differ mainly in the sequences
      located in the hinge region. IgA molecules, whose hinge regions are remarkably
      similar to those of the respective human molecules, are present in hominoid
      primates. In this report, we show that two alleles of a single immunoglobulin C
      alpha are present in rhesus macaques (Macaca mulatta). In addition, we show that
      intraspecies immunoglobulin C alpha allelic polymorphism is very high in this non
      human primate species. Specifically, five different hinge regions, some of which
      are proline-rich, were identified from a total of eight rhesus macaque
      immunoglobulin C alpha-chains. The five hinge regions were different from those
      present in hominoid primates, both in length and in sequence. These results
      represent the first example of high levels of intraspecies immunoglobulin
      constant-region variability and suggest that IgAs of variable structure and
      function may be present in rhesus macaques. As rhesus macaques are widely used as
      animal models for the development of vaccines for acquired immune deficiency
      syndrome (AIDS), the possible presence of structurally and functionally variable
      IgA molecules in different animals should be taken into account when designing
      experimental strategies to induce mucosal antibody responses to human
      immunodeficiency virus (HIV).

PMID- 11529935
TI  - Interleukin-10 expressed at early tumour sites induces subsequent generation of
      CD4(+) T-regulatory cells and systemic collapse of antitumour immunity.
AB  - We investigated the relationship between transforming growth factor-beta (TGF
      beta)-secreting T-regulatory (Tr) cells and anti-B16 melanoma immunity, and
      studied the association of early cytokines expressed at tumour sites with the
      generation of Tr cells. A large number of CD4(+) Tr cells producing interleukin
      (IL)-4, IL-10 and TGF-beta accumulated with functionally depressed CD8(+)
      cytotoxic T lymphocytes (CTLs) at tumour sites on day 20 after subcutaneous
      (s.c.) inoculation of B16 tumour cells. Tr cells consisted of two populations,
      which were termed T helper 3 (Th3) and Tr1 cells. B16-infiltrating Tr cells
      strongly inhibited the generation of B16-specific T helper 1 (Th1) cells in a TGF
      beta-dependent manner and were assumed to suppress effective generation of CTLs.
      In addition, B16 cells markedly progressed in mice transferred adoptively by the
      cultured B16-infiltrating Tr cells compared with untreated mice. The capacity of
      these Tr cells to produce TGF-beta was hampered by neutralizing anti-IL-10 and
      partly anti-IL-4 monoclonal antibodies (mAbs) injected intralesionally during the
      early development of B16 tumours, and this treatment markedly attenuated B16
      growth. Furthermore, a lesional injection of recombinant mouse IL-10 at an early
      tumour site resulted in the vigorous progression of B16 tumours. These results
      provide evidence that Tr cells, belonging to the T helper 3/T-regulatory 1
      (Th3/Tr1) type, are activated in B16-bearing hosts under the influence of T
      helper 2 (Th2) cytokines, mainly IL-10 (produced at early tumour lesions), and
      that this regulatory T-cell population functions as a suppressor of anti-B16
      immunity.

PMID- 11529936
TI  - Interleukin-10-secreting Peyer's patch cells are responsible for active
      suppression in low-dose oral tolerance.
AB  - We demonstrate the induction of antigen-specific interleukin-10 (IL-10)-secreting
      cells in murine Peyer's patches (PPs) after low-dose beta-lactoglobulin (BLG)
      feeding. In addition, we show that PP cells can inhibit the T-cell proliferative
      response in vitro as well as T-cell-mediated inflammation in vivo. The active
      suppression mediated by these regulatory cells was seen only within a narrow
      range of antigen dosage (feeding), with the most prominent effect at 5 x 1 mg
      BLG. On either side of this range, T-helper 1-like cytokine responses were
      observed when PP cells were stimulated with antigen in vitro. This result
      correlated with reduced production of regulatory cytokines as well as reduced
      activity of bystander suppression. We found that changes in IL-10 production
      correlated inversely with changes in interferon-gamma production. Inhibitory
      effects mediated by CD4(+) PP cells were partially neutralized by antibodies to
      IL-10 and transforming growth factor-beta. Interestingly, the generation of such
      regulatory cells after low-dose BLG feeding exhibited organ dependence. Among
      spleen, lymph node and PP cells derived from orally tolerized mice, PP cells were
      the most effective in promoting bystander suppression in the presence of BLG,
      indicating the significance of PPs as an inductive site for antigen-specific
      regulatory cells upon induction of low-dose oral tolerance. Moreover, PP cells
      from mice fed 5 x 1 mg BLG were shown to suppress a BLG-specific delayed-type
      hypersensitivity response induced in footpads, suggesting that IL-10-secreting PP
      cells regulate systemic inflammation.

PMID- 11529937
TI  - Tumour necrosis factor-alpha potentiates CR3-induced respiratory burst by
      activating p38 MAP kinase in human neutrophils.
AB  - CR3 and Fc gamma Rs are the main receptors involved in the phagocytic process
      leading to engulfment and killing of microbes by production of reactive oxygen
      intermediates (ROI) and degranulation. Various inflammatory mediators, such as
      tumour necrosis factor-alpha (TNF-alpha) and lipopolysaccharide (LPS), are known
      to prime neutrophils leading to increased bactericidal responses, but the
      underlying mechanism of priming has only been partially elucidated. The purpose
      of this study was to investigate how TNF-alpha primes neutrophils for subsequent
      stimuli via either CR3 or Fc gamma R. The receptors were specifically activated
      with pansorbins (protein-A-positive Staphylococcus aureus) coated with anti-CR3,
      anti-Fc gamma RIIa, or anti-Fc gamma RIIIb monoclonal antibody. Activation of
      neutrophils with these particles resulted in ROI production as measured by
      chemiluminescence. Anti-CR3 pansorbins induced the most prominent ROI production
      in neutrophils. TNF-alpha potentiated the CR3-mediated respiratory burst but had
      little effect on that mediated by Fc gamma Rs. The priming effect of TNF-alpha on
      CR3-mediated ROI production is associated with an increased activation of p38
      MAPK as well as tyrosine phosphorylation of p72(syk). Pretreatment of neutrophils
      with the inhibitors for p38 MAPK and p72(syk) markedly suppressed the respiratory
      burst induced by CR3. Furthermore, TNF-alpha induced about a three-fold increase
      in the expression of CR3 in neutrophils, an effect which is blocked by the p38
      MAPK inhibitor. Taken together, these results showed that TNF-alpha potentiates
      the CR3-mediated respiratory burst in neutrophils not only by triggering a p38
      MAPK-dependent up-regulation of CD11b/CD18 but also by modulating the signalling
      pathways.

PMID- 11529938
TI  - Sulphasalazine inhibits macrophage activation: inhibitory effects on inducible
      nitric oxide synthase expression, interleukin-12 production and major
      histocompatibility complex II expression.
AB  - The anti-inflammatory agent sulphasalazine is an important component of several
      treatment regimens in the therapy of ulcerative colitis, Crohn's disease and
      rheumatoid arthritis. Sulphasalazine has many immunomodulatory actions, including
      modulation of the function of a variety of cell types, such as lymphocytes,
      natural killer cells, epithelial cells and mast cells. However, the effect of
      this agent on macrophage (M phi) function has not been characterized in detail.
      In the present study, we investigated the effect of sulphasalazine and two
      related compounds - sulphapyridine and 5-aminosalicylic acid - on M phi
      activation induced by bacterial lipopolysaccharide (LPS) and interferon-gamma
      (IFN-gamma). In J774 M phi stimulated with LPS (10 microg/ml) and IFN-gamma (100
      U/ml), sulphasalazine (50-500 microM) suppressed nitric oxide (NO) production in
      a concentration-dependent manner. The expression of the inducible NO synthase
      (iNOS) was suppressed by sulphasalazine at 500 microM. Sulphasalazine inhibited
      the LPS/IFN-gamma-induced production of both interleukin-12 (IL-12) p40 and p70.
      The suppression of both NO and IL-12 production by sulphasalazine was superior to
      that by either sulphapyridine or 5-aminosalicylic acid. Although the combination
      of LPS and IFN-gamma induced a rapid expression of the active forms of p38 and
      p42/44 mitogen-activated protein kinases and c-Jun terminal kinase,
      sulphasalazine failed to interfere with the activation of any of these kinases.
      Finally, sulphasalazine suppressed the IFN-gamma-induced expression of major
      histocompatibility complex class II. These results demonstrate that the M phi is
      an important target of the immunosuppressive effect of sulphasalazine.

PMID- 11529939
TI  - Enhanced maturation and functional capacity of monocyte-derived immature
      dendritic cells by the synthetic immunomodulator Murabutide.
AB  - Murabutide is a safe synthetic immunomodulator derived from muramyl dipeptide,
      the smallest bioactive unit of bacterial peptidoglycan. Although it is well known
      that muramyl peptides modulate the functions of monocytes/macrophages, their
      activity on dendritic cells is poorly documented. We thus investigated the
      effects of Murabutide on immunophenotype, endocytosis, T-cell stimulatory
      capacity, and cytokine secretion of human monocyte-derived immature dendritic
      cells (iDCs). We found that Murabutide triggers immunophenotypic changes as upon
      treatment, iDCs up-regulate the surface expression of the major
      histocompatibility complex type II molecule human leucocyte antigen-DR, the co
      stimulatory molecules CD80, CD86 and CD40 and the differentiation marker CD83,
      and down-regulate the expression of the mannose receptor. These phenotypic
      changes are also mirrored by changes in their biological activity. Subsequent to
      treatment with the synthetic immunomodulator, DC have a decreased endocytic
      capacity but exhibit enhanced stimulatory capacity for both allogeneic and
      autologous T cells. In addition, Murabutide-stimulated iDCs have a greater
      cytostatic activity toward the tumour cell line THP-1. Furthermore, in the
      presence of Murabutide, DCs transiently increased the release of macrophage
      inhibitory protein-1 beta, tumour necrosis factor-alpha and interleukin-10,
      whereas the enhanced production of macrophage-colony stimulating factor was
      sustained over the 3-day period analysed. In addition, Murabutide triggers the
      phosphorylation of the three classes of mitogen-activated protein kinases in
      iDCs. Altogether our results demonstrate that Murabutide triggers the maturation
      and activation of monocyte-derived iDCs. As this immunomodulator is approved for
      administration in humans, it could be a useful adjunct to boost the efficacy of
      DC-based vaccines designed against tumours or virus-infected cells.

PMID- 11529940
TI  - Lipopolysaccharide and phorbol 12-myristate 13-acetate both impair monocyte
      differentiation, relating cellular function to virus susceptibility.
AB  - Both lipopolysaccharide (LPS) and phorbol 12-myristate 13-acetate (PMA) impeded
      monocyte to macrophage differentiation with respect to typical phenotypic
      modulation and certain phagocyte-related processes. The down-regulation of the
      porcine monocyte marker SWC1, and up-regulation of the SWC9 macrophage marker
      were retarded, but not inhibited, as was the differentiation-associated down
      regulation of p53 and myeloperoxidase. Despite this clear impairment of
      macrophage differentiation, not all cellular functions were equally susceptible.
      Both agents inhibited phagocytosis, but not low-density lipoprotein receptor
      associated endocytosis. Only LPS inhibited tartrate-resistant acid phosphatase up
      regulation. In contrast, increase of vacuolar acidification rates was more
      susceptible to PMA. The activity of certain endosomal/lysosomal enzymes -
      esterase, nucleotidase, peroxidase and cathepsins - was generally enhanced by
      both LPS and PMA. This contrasted with autophagosomal activity, detected through
      the induction of an antiviral state. Disruption of autophagosomes and lysosomes
      (methionine-O-methyl ester), but not lysosomes alone (glycyl-L-phenylalanine)
      reversed LPS-induced inhibition of virus replication, without influencing the PMA
      induced antiviral effect. Thus, PMA is similar to LPS in inhibiting monocyte to
      macrophage differentiation, when primary blood monocytes are employed, but not
      all pathways are equally susceptible. The analyses demonstrate that the pathways
      modulated during monocyte differentiation function somewhat independently.
      Moreover, certain functions of monocytic cells are more important with respect to
      the outcome of virus infection, with autophagosomal activities in particular
      favouring cell survival.

PMID- 11529942
TI  - Leucocyte recruitment during enteric nematode infection.
AB  - Resolution of infection with the intestinal nematode Trichinella spiralis depends
      on the host mounting a T helper 2 (Th2) response. It is known that both mast
      cells and T cells play a crucial role. We have previously shown that efficient
      migration of mast cells to the gut during infection depends on their expression
      of the integrin beta 7. beta 7 forms a heterodimer complex with either alpha E or
      alpha 4 integrin chains, alpha E beta 7 binding to E-cadherin expressed by
      epithelial cells and alpha 4 beta 7 binding to mucosal addressin cell adhesion
      molecule (MAdCAM-1) on the endothelium. We were interested to know whether
      dysfunctional mast cell localization to the gut in the absence of beta 7 was due
      to the failure of alpha 4 beta 7 to bind to MAdCAM-1 or the failure of alpha E
      beta 7 to bind to E-cadherin. We used blocking monoclonal antibodies against
      alpha E (M290) or alpha 4 (PS2) or beta 7 (HB293) during T. spiralis infection of
      C57BL/6 mice and found that all antibody treatments reduced mastocytosis. In
      contrast, none of the antibody treatments prevented the migration of CD3(+) T
      cells into the intestine. These results indicate that during inflammation (a)
      there is integrin redundancy for lymphocytes but not for mast cells and (b) both
      alpha E beta 7 and alpha 4 beta 7 are crucial either for the entry of mast cells
      into the gut or for their maturation once they have entered.

PMID- 11529943
TI  - Interferon-gamma is crucial for surviving a Brucella abortus infection in both
      resistant C57BL/6 and susceptible BALB/c mice.
AB  - Brucella abortus is an intracellular bacterial pathogen that causes chronic
      infections in humans and a number of agriculturally important species of animals.
      It has been shown that BALB/c mice are more susceptible to infections with
      virulent strains of Brucella abortus than C57BL/6 or C57BL/10 strains. In
      experiments described here, gene knock-out mice were utilized to elucidate some
      of the salient components of resistance. Resistant C57BL/6 mice with gene
      deletions or disruptions in the interferon-gamma (IFN-gamma), perforin or beta(2)
      microglobulin genes had decreased abilities to control intracellular infections
      with B. abortus strain 2308 during the first week after infection. However, only
      the IFN-gamma knock-out mice had a sustained inability to control infections and
      this resulted in death of the mice at approximately 6 weeks post-infection. These
      mice had a continual increase in the number of bacterial colony-forming units
      (CFU) in their spleens until death. When BALB/c mice with the disrupted IFN-gamma
      gene were infected they had more splenic CFU at one week post-infection than
      control mice but the increase was not statistically significant and by 3 weeks
      they did not have more CFU than control mice. Moreover, the number of splenic
      bacteria did not increase in the BALB/c IFN-gamma knock-out mice between 6 and
      10.5 weeks, although they died at 10.5 weeks, the time by which normal BALB/c
      mice were clearing the infection. Death in both strains of IFN-gamma gene
      disrupted mice coincided with symptoms of cachexia and macrophages comprised >
      or= 75% of the splenic leucocytes.

PMID- 11529941
TI  - Characterization of equine E-selectin.
AB  - Expression of E-selectin on activated endothelium is a critical initial step that
      leads to extravasation of leucocytes during inflammation, yet E-selectin is
      largely uncharacterized in several animal species including the horse. We have
      sequenced and compared E-selectin genes derived from activated cultures of
      purified equine (horse), cervid (black-tailed deer) and ovine (sheep) pulmonary
      artery endothelial cells (ECs). Phylogenetic and amino acid sequence comparisons
      indicate that bovine, cervid and ovine E-selectin are similar, whereas human and
      equine E-selectin are more closely related to each other than to the ruminant
      molecules. Human E- and P-selectin-specific monoclonal antibodies that also
      recognize equine E-selectin were identified and used to characterize its
      expression. Expression of E-selectin was more readily induced by
      lipopolysaccharide treatment in equine ECs than in human ECs and supported
      adhesion and activation of neutrophils, consistent with the extreme sensitivity
      of horses to endotoxaemia and septic shock.

PMID- 11529944
TI  - Bactericidal/permeability-increasing protein promotes complement activation for
      neutrophil-mediated phagocytosis on bacterial surface.
AB  - The neutrophil bactericidal/permeability-increasing protein (BPI) has both
      bactericidal and lipopolysaccharide-neutralizing activities. The present study
      suggests that BPI also plays an important role in phagocytosis of Escherichia
      coli by neutrophils through promotion of complement activation on the bacterial
      surface. Flow cytometric analysis indicated that fluorescein-labelled E. coli
      treated with BPI were phagocytosed in the presence of serum at two- to five-fold
      higher levels than phagocytosis of the bacteria without the treatment. In
      contrast, phagocytosis of the fluoresceined bacteria with or without treatment by
      BPI did not occur at all in the absence of serum. The phagocytosis stimulated by
      BPI and serum was dose-dependent. The effect of BPI on phagocytosis in the
      presence of serum was not observed on Gram-positive bacteria (Staphylococcus
      aureus). Interestingly, the complement C3b/iC3b fragments were deposited onto the
      bacterial surface also as a function of the BPI concentration under conditions
      similar to those for phagocytosis. Furthermore, the BPI-promoted phagocytosis was
      blocked completely by anti-C3 F(ab')(2) and partially by anti-complement receptor
      (CR) type 1 and/or anti-CR type 3. These findings suggest that BPI accelerates
      complement activation to opsonize bacteria with complement-derived fragments,
      leading to stimulation of phagocytosis by neutrophils via CR(s).

PMID- 11529946
TI  - Psychological aspects of breast reconstruction: a review of the literature.
AB  - AIM: This paper critically examines the research literature relating to the
      psychological aspects of breast reconstruction. Particular attention is given to
      the role of specialist breast care nurses in supporting women faced with the
      decision of whether or not to opt for reconstructive surgery. BACKGROUND: Breast
      reconstruction is intended to offer psychological benefits (e.g. improvements to
      quality of life, body image, anxiety and depression) to women treated by
      mastectomy following diagnosis of breast cancer. METHODS: A literature search was
      carried out on the PSYCHINFO, MEDLINE and CINAHL databases using the terms
      "breast reconstruction", "mastectomy", "reconstructive surgery", "breast
      surgery", "breast implants", "transverse rectus adominis myocutaneous (TRAM)
      flap" and "Lat-dorsi". Further relevant articles were identified from the
      reference lists of papers detected by this literature search. Finally,
      proceedings of recent psychological and surgical meetings were scrutinized to
      identify any conference papers on this topic. FINDINGS: A thorough search of the
      existing literature revealed a lack of theoretically based studies examining
      breast reconstruction in terms of relevant psychological constructs, especially
      in relation to coping and decision-making. This review highlights the
      methodological flaws with much of the existing research in this area, in
      particular the reliance upon retrospective designs and the inappropriate use of
      randomised controlled trials. Suggestions are given for further research in this
      topical area. CONCLUSIONS: Existing research into the psychological aspects of
      breast reconstruction is limited and not sufficiently conclusive to inform
      changes to policy and the provision of care. More methodologically rigorous
      research is needed.

PMID- 11529947
TI  - A critique of research on the use of activities with persons with Alzheimer's
      disease: a systematic literature review.
AB  - TOPIC: The topic of this paper concerns the use of therapeutic activities with
      persons with Alzheimer's disease (AD). PURPOSE: The purpose is to present a
      critique of the research on these activities, with an emphasis on methodology.
      ORGANIZING CONSTRUCT AND SCOPE: Nursing literature identifies a number of
      purposes for activities for persons with AD. Activities should be therapeutic,
      enhance quality of life, arrest mental decline, and generate and maintain self
      esteem. Other purposes of activities for this population are to create immediate
      pleasure, re-establish dignity, provide meaningful tasks, restore roles, and
      enable friendships. Activities may be more important to the psychological state
      of well-being of persons with dementia than the general physical and social
      environments in which they live. SOURCES: The literature reviewed was identified
      with the use of computer data bases (Medline - 1991-March 2001; Cumulative Index
      of Nursing and Allied Health Literature (CINAHL) - 1991-March 2001; and PsychLit 
      1988-March 1999). In addition, data bases of Science Citation Index and Social
      Science Citation Indexes as they appear in the computer base, Web of Science,
      were searched for 1992-2001. The time period for each search was determined by
      the manner in which the literature was grouped for inclusion in the particular
      database. Hand searches of 11 selected journals included the years 1993-2001. The
      search dates were selected to reflect the time period when the largest number of
      studies on activities and AD have appeared in the professional literature. We
      critique a total of 33 studies. CONCLUSIONS: While researchers have demonstrated
      interest in the use of activities with persons with AD, theoretical and
      methodological difficulties, unclear findings and gaps exist, including a lack of
      emphasis on gender, ethnic, racial or cultural differences. Sampling issues
      involving diagnosis and staging complicate the research on individuals with AD.
      Case studies, single subject experimental designs, and tightly controlled quasi
      experimental and experimental designs are needed to advance knowledge in this
      important area.

PMID- 11529948
TI  - Information and support needs of women with primary relatives with breast cancer:
      development of the Information and Support Needs Questionnaire.
AB  - AIMS OF THE STUDY: The aim was to develop and pilot test a newly developed
      measure, The Information and Support Needs Questionnaire (ISNQ), for use with
      women with primary relatives with breast cancer. BACKGROUND/RATIONALE: Breast
      cancer is a major risk to the health of women in the United Kingdom (UK).
      Increasingly, research is documenting women's needs for information and support,
      particularly at the time of diagnosis. However, to date there is little
      understanding of the information and support needs of women who have a family
      history of breast cancer. Contributing to the dearth of understanding of female
      relatives' needs is the lack of valid and reliable instruments for use in
      descriptive and intervention research with this population. DESIGN/METHODS: The
      ISNQ and survey items documenting family history, sources of information and
      support for breast cancer risk, breast self-care practices, and other variables
      were pilot tested for the acceptability of the measures, appropriateness of the
      data collection methods, initial psychometric properties of the ISNQ, and time
      and financial costs of administration. Data were collected from 39 women living
      in the North-west of England who had primary relatives with breast cancer using
      mailed questionnaires and follow-up telephone interviews. FINDINGS: The items on
      the ISNQ were reported to be clear, acceptable to women and to yield relevant
      data. The psychometric properties of the new measure were satisfactory with a
      high reliability coefficient alpha. Descriptive findings indicate that women had
      moderate to high needs for information and support, but reported that these needs
      were not well met. CONCLUSIONS: The results of this pilot are guiding the
      development of a larger study in which the information and support needs of women
      with a family history of breast cancer are explored.

PMID- 11529949
TI  - The Data Protection Act (1998): implications for health researchers.
AB  - AIMS: This paper reports on the methods used in two studies to obtain access to
      subjects to comply with the common law duty of confidence laid out in the Data
      Protection Act (1998) and discusses the researchers' problems in interpreting the
      procedures. RATIONALE: The amendments to the United Kingdom (UK) Data Protection
      Act (1998) are causing confusion within the health service and academic
      institutions. There is a need to balance patient confidentiality with the
      requirement to conduct vital, unbiased research in which health service
      professionals are not subject to ethical dilemmas. This paper examines the
      recruitment methods used in two studies in which the researchers' attempts to
      adhere to the requirements lengthened the study costs and may have produced less
      reliable results. METHODS: The methodological difficulties in two studies are
      presented. In Study 1, the difficulties encountered when the Multicentre Research
      Ethics Committee refused permission for researchers to recruit patients directly
      to a multicentre randomized controlled trial are discussed. In Study 2, the
      method used to compile a sampling frame for a national questionnaire survey
      following the eight principles of the Act are described. FINDINGS: Our experience
      has shown that health care professionals are increasingly required to recruit
      patients to intervention trials, and that researchers are not allowed access to
      the names of patients or other subjects to ask them for consent to participate in
      a study. The requirement for researchers to use "intermediaries" to obtain
      consent from and recruit subjects to studies increases the risk of selection
      bias, may expose the practitioner to ethical difficulties and may compromise the
      external validity of trial results. There is also a danger that research costs
      will soar when the Data Protection Act (1998) is fully realized. CONCLUSION: The
      Data Protection Act (1998) is currently being interpreted in a number of
      different ways. We conclude there is an urgent need for consensus within the
      health service and academic communities.

PMID- 11529950
TI  - Planning strategies for the avoidance of pitfalls in intervention research.
AB  - BACKGROUND: With the exception of large clinical trials, few studies in nursing
      and other social sciences test interventions. The discipline of nursing needs to
      maintain a full range of research designs for continued knowledge development.
      Intervention research presents unique opportunities and challenges for the novice
      as well as the seasoned researcher. Some of these methodological challenges
      include the complex nature of human subjects and interventions, including many
      factors that interfere with the study variables. Preliminary studies often reveal
      challenges that may not always be predicted or reflected in research texts. These
      challenges may be as important as the study results for success in future
      research efforts. PURPOSE: Difficulties encountered in intervention research and
      suggested strategies for maintaining the integrity of the study are addressed.
      These challenges include maintaining an adequate sample size, intervention
      demands, measuring variables, timing issues, and experiencing unexpected events.
      FINDINGS AND CONCLUSIONS: Strategies presented include the importance of
      extensive planning, minimizing subject expectations and rewarding efforts,
      attention to control group members, incorporating retention strategies, expanding
      knowledge of variables and the study population, preliminary studies as well as
      anticipating unexpected events. The need for enhanced communication among nurse
      researchers, educators and clinicians is addressed. In the current health care
      arena, nurse researchers must understand organizational dynamics and marketing
      strategies. Collaborative research efforts can increase the visibility of nursing
      research as well as funding opportunities.

PMID- 11529951
TI  - Triangulation using a meta-matrix.
AB  - BACKGROUND AND SIGNIFICANCE: Quantitative and qualitative data analysis are often
      undertaken as separate enterprises, as they emerge from differing philosophies of
      science and methodologies for data collection, management and analysis.
      Quantitative data analysis is sometimes seen in philosophic and methodologic
      conflict with a naturalistic, human science perspective of science. Researchers
      interested in data from both realms often rely on triangulation procedures, in
      which each is considered from its representative lens. Results are then projected
      out into a common area where data are melded and discussed. The purpose of this
      paper is to introduce the meta-matrix as a tool for triangulation in nursing
      research and to demonstrate its usefulness in an exemplar case. DESIGN/METHODS:
      The exploratory nature of a recent study led to the decision to manage
      triangulation using an emerging methodology, thereby allowing consideration of
      all data simultaneously through the use of a meta-matrix. Discussion of the meta
      matrix as a method is presented. FINDINGS: Use of the meta-matrix facilitated
      data analysis and allowed pattern recognition across data sets. Discovery of
      several unexpected relationships deepened understanding of the results and
      assisted in identifying questions for further research. CONCLUSIONS/IMPLICATIONS:
      The meta-matrix method provides a useful alternative approach for secondary-level
      data analysis in mixed-methods research.

PMID- 11529952
TI  - Cohesion among nurses: a comparison of bedside vs. charge nurses' perceptions in
      Australian hospitals.
AB  - AIM: This study examines the extent to which hospital nurses view their working
      environment in a positive sense, working as a cohesive group. BACKGROUND: Despite
      the fact that nursing in Australia is now considered a profession, it has been
      claimed that nurses are an oppressed group who use horizontal violence, bullying
      and aggression in their interactions with one and other. METHODS: After ethical
      approval, a random sample of 666 nurses working directly with patients and all
      333 critical care nurses employed in three large tertiary Australian hospitals
      were invited to participate in the study in the late 1990s. A mailed survey
      examined the perceptions of interaction nurses had with each other. The
      hypothesis, that level of employment (either Level I bedside nurses or Level
      II/III clinical leaders) and area of work (either critical care or noncritical
      care) would influence perceptions of cohesion, as measured by the cohesion
      amongst nurses scale (CANS) was tested. RESULTS: In total 555 (56%) surveys were
      returned. Of these, 413 were returned by Level I and 142 by Level II/III nurses.
      Of this sample, 189 were critical care and 355 noncritical care nurses. There was
      no difference between Level I and II/III nurses in mean CANS scores. It is
      interesting to note that the item rated most positively was "nurses on the units
      worked well together", however, the item rated least positive was "staff can be
      really bitchy towards each other" for both Level I and II/III nurses. There was
      no difference in CANS scores between critical care and noncritical care nurses.
      CONCLUSIONS: Nurses working in Australian hospitals perceived themselves to be
      moderately cohesive but, as would be expected in other work settings, some
      negative perceptions existed.

PMID- 11529953
TI  - Leadership, organizational stress, and emotional exhaustion among hospital
      nursing staff.
AB  - STUDY'S RATIONALE AND OBJECTIVES: We examined the effect of work stressors and
      head nurses' transactional and transformational leadership on the levels of
      emotional exhaustion experienced among their staff. METHODOLOGICAL DESIGN AND
      RESEARCH METHODS: A questionnaire was sent to all nurses of a university
      hospital. Usable returns were received from 625 nurses, giving a response rate of
      39.2%. Data were treated using correlational analyses and multiple regression.
      The latter modelled stressors and leadership as predictors of nurses' reported
      emotional exhaustion. MEASURES: Work stressors were assessed using the Nursing
      Stress Scale (NSS) which comprises 34 items divided into three subscales
      (referring to stress from the physical, psychological, and social environment),
      and the role ambiguity (three items) and conflict (three items) scales.
      Leadership was measured with the Multifactor Leadership Questionnaire. RESULTS:
      In regression analyses, work stressors as a whole were found to explain 22% of
      the variance in emotional exhaustion whereas leadership dimensions explained 9%
      of the variance in that outcome measure. Stress emanating from the physical and
      social environment, role ambiguity, and active management-by-exception leadership
      were significantly associated with increased levels of emotional exhaustion.
      Transformational and contingent reward leadership did not influence emotional
      exhaustion. LIMITATIONS: A limitation of this study is that it considered only
      the emotional exhaustion dimension of burnout. Also, as data were cross-sectional
      in nature, conclusions regarding the direction of causality among variables
      cannot be drawn. CONCLUSIONS: This study provided, for the first time, a test of
      the influence of leadership on burnout among nurses, taking into account the role
      of work stressors. Future research is needed to examine if the effects reported
      herein can be replicated using the two other dimensions of burnout
      (depersonalization and reduced personal accomplishment).

PMID- 11529954
TI  - The wartime experience of Australian Army nurses in Vietnam, 1967-1971.
AB  - AIMS: To provide a synthesis of the experience of nursing in the Vietnam War.
      RATIONALE: War and nursing are linked unequivocally. As battles have raged over
      the centuries, nurses have attended the ill and wounded soldiers, nursing them
      back to health or into death and the study of this phenomenon forms a significant
      part of Australia's nursing history. However, a review of the Australian
      scholarly nursing and military history literature revealed that the experiences
      of Australian nurses in the Vietnam War has not been widely published. In an
      attempt to redress this gap in Australian nursing and military history, the aim
      of this study was to analyse the nature of the nursing work in the Vietnam War,
      and to increase awareness and understanding of the experience of nurses in the
      war within the nursing profession. METHODS: Using oral history interviews, this
      study investigated the nature of nursing work as experienced by 17 Australian
      Army nurses who served in the Australian Military Hospital in Vung Tau between
      1967 and 1971. FINDINGS: The vast majority of the nursing sisters sent to Vietnam
      knew little about the type of work or the environment into which they were
      entering and were, therefore, clinically unprepared. It appeared that, by virtue
      of their being a nurse, it was an expectation that the nurses would adapt to the
      nature of their work in the war zone. However, this study also revealed that,
      although the nurses adapted professionally, their memories of their experiences
      have affected many personally. CONCLUSIONS: This paper will increase current
      knowledge significantly regarding the phenomenon of nursing in the Vietnam War,
      enabling a greater understanding of the experience.

PMID- 11529955
TI  - Triage nurses' clinical decision making. An observational study of urgency
      assessment.
AB  - BACKGROUND: Researchers have described both the various decision tasks performed
      by triage nurses using self-report methods and identified time as a factor
      influencing the quality of triage decisions. However, little is known about the
      decision tasks performed by triage nurses when making acuity assessments, or the
      factors influencing triage duration in the real world. AIMS: The aims of this
      study were to: describe the data triage nurses collect from patients in order to
      allocate a triage priority using the Australasian Triage Scale (ATS); describe
      the duration of nurses' decision making for ATS categories 2-5; and to explore
      the impact of patient and nurse variables on the duration of the triage nurses'
      decision making in the clinical setting. DESIGN: A structured observational study
      was employed to address the research aims. Observational data was collected in
      one adult emergency department located in metropolitan Melbourne, Australia. A
      total of 26 triage nurses consented and were observed performing 404 occasions of
      triage. Data was collected by a single observer using a 20-item instrument that
      recorded the performance frequencies of a range of decision tasks and a number of
      observable patient, nurse and environmental variables. Additionally, the nurse
      patient interaction was recorded as time in minutes. RESULTS: It was found that
      there was limited use of objective physiological data collected by the nurses' in
      order to decide patient acuity, and large variability in the duration of triage
      decisions observed. In addition, analysis of variance indicated strong evidence
      of a true difference between triage duration and a range of nurse, patient and
      environmental variables. CONCLUSION: These findings have implications for the
      development of practice standards and triage education. In particular, it is
      argued that practice standards should include routine measurement of
      physiological parameters in all but the collapsed or obviously unwell patient,
      where further delay may impede the delivery of time-critical intervention.
      Furthermore, the inclusion of arbitrary time frames for triage assessment in
      practice standards are not an appropriate method of evaluating triage decision
      making in the real world.

PMID- 11529956
TI  - Exploring Spanish emergency nurses' lived experience of the care provided for
      suddenly bereaved families.
AB  - AIM OF THE STUDY: To investigate the experience of emergency nurses caring for
      suddenly bereaved family members in the clinical setting, particularly after they
      are informed about the loss of a loved one. DESIGN/METHODS: Data was obtained
      from semi-structured interviews with seven emergency nurses drawn from emergency
      nursing staff working in a Spanish Hospital. Interviews were tape recorded, and
      hermeneutic-phenomenological analysis was applied to gain understanding from the
      emergency nurses' experiences. SETTING: The Accident and Emergency department in
      the Hospital Universitario Insular de Gran Canaria (Spain). Study undertaken in
      partial fulfillment of the main author's MSc (Department of Nursing and Community
      Health) at Glasgow Caledonian University. RESULTS: Several themes emerged from
      those interviews, which appeared to form the basis of the emergency nurses'
      reality: knowing, relationships, culture and reality. They showed the need to
      reflect on personal and professional experiences to facilitate personal growth,
      discover meaning for emergency nurses and examine the possible implications for
      clinical care. CONCLUSIONS: This study enabled both participants and the
      researcher to evaluate critically what was troublesome from their perspective and
      to identify sources of innovation and liberation within everyday practices.

PMID- 11529957
TI  - Components of a proper hospital discharge for elders.
AB  - SIGNIFICANCE: Effective discharge planning is a vital link in continuity of care
      for elders. Previous studies identify problems with planning for elders'
      discharge from the hospital and problems elders encounter managing care post
      discharge. However, little attention has been given to identifying effective
      discharge planning processes. Explicating the components of effective discharge
      planning is critical to replicate the process in other health care settings and
      predict post-discharge outcomes. PURPOSE: The purpose of this study was to
      identify the components of effective discharge planning for elders and factors
      that impede planning. METHODS: Ethical approvals were obtained from the
      University and National Health Service (NHS) Trust. Qualitative methods were used
      and data were collected from two wards in a 78-bed geriatric rehabilitation
      hospital that was part of a National Health Service Trust serving Southwest
      London. Data included semi-structured interviews and documents related to
      discharge planning, care delivery, and community resources. A total of 24 semi
      structured interviews were conducted with health care professionals who were part
      of the hospital's multidisciplinary team, those affiliated with the Community
      Trust that provided aftercare, elders, and family carers. RESULTS: Participants
      consistently used the term "proper discharge" when referring to effective
      discharge planning. The multidisciplinary team comprised a vital context for a
      proper discharge. The findings indicated that three circles of communication were
      central in a four stage discharge process. Different circles of communication
      were key at different stages. CONCLUSIONS: The findings provide insights for
      educating nurses about effective planning practices and examining the global
      significance of impediments to a proper hospital discharge.

PMID- 11529958
TI  - The nurse--a resource in hypertension care.
AB  - AIM OF THE STUDY: To explore the content and structure of communication between
      patient and nurse at follow-up appointments concerning hypertension. BACKGROUND:
      Hypertension is a chronic condition and calls for co-operation between health
      care providers and patients over a long period of time. One important purpose of
      the follow-up consultations is to transfer knowledge between patients and health
      care providers in order to empower patients. This is an important determinant of
      the quality of care. DESIGN/METHODS: The study was based on 20 audio-recordings
      of actual follow-up appointments and was approved by ethics committees. The
      consultations took place at four different health care units for hypertensive
      patients. FINDINGS: The average length of consultations was 18 minutes. In the
      consultations, patients initiated an average of eight new topics and nurses an
      average of 20. All nurses talked with patients about life style. Compared with
      previous studies of follow-ups with physicians, consultations with nurses
      addressed lifestyle factors and adherence to treatment to a higher degree. It was
      also observed that patients were more actively involved in interaction with
      nurses compared with the follow-ups with physicians. CONCLUSIONS: Active patient
      participation in care is a critical factor in improving adherence to treatment.
      It would be of value to develop and assess a more patient-centred organization of
      hypertension care and thereby more individualized hypertension treatment. Nurses
      may have a pivot role in such care.

PMID- 11529959
TI  - The implementation of a Pain Monitoring Programme for nurses in daily clinical
      practice: results of a follow-up study in five hospitals.
AB  - AIMS OF THE STUDY: To study the effects of the implementation of a Pain
      Monitoring Programme (PMP) for nurses in daily clinical practice. In addition,
      nurses' and physicians' pain knowledge and attitudes were studied, as well as
      change in nurses' pain knowledge after implementation of the programme.
      RATIONALE: The rationale for the study was that many hospitalized patients suffer
      from pain and treatment of pain is often inadequate. BACKGROUND: Reasons for
      inadequate treatment of pain are the failure of nurses to assess pain on a daily
      basis and insufficient knowledge about pain and pain management in both nurses
      and physicians. The PMP tried to overcome these barriers by implementing daily
      pain assessment and educating nurses about pain and pain management. RESEARCH
      METHODS: This follow-up study was conducted in five hospitals. In total, 277
      nurses and 115 physicians participated. The implementation and long-term effects
      of the programme were measured with a pretest-post-test design without a control
      group. RESULTS: Results showed that nurses carried out daily pain assessment in
      at least 75% of patients during the first 5 months of the intervention period,
      but in the remaining 2 months professional compliance gradually decreased. Both
      nurses and physicians are positive about daily pain assessment and want to
      continue with it. The level of nurses' and physicians' knowledge about pain and
      pain management is moderate. The programme increased nurses' knowledge and
      satisfaction regarding the quality of pain treatment. DISCUSSION: Because
      professional compliance decreased after 5 months, incentives are needed to
      motivate nurses to continue with daily pain assessment. Continuous Quality
      Improvement may be a useful method to guide the implementation process.
      CONCLUSIONS: Based on these results it can be concluded that it is possible to
      implement the PMP in daily clinical practice. Moreover, the beneficial effects of
      our programme on nurses' knowledge and attitudes have been demonstrated.
      Therefore, participating hospitals were advised to continue and extend the
      programme and other hospitals are encouraged to implement it.

PMID- 11529960
TI  - Midwives' attitudes to the use of the cardiotocograph machine.
AB  - BACKGROUND: The literature would suggest that midwives' attitudes towards the use
      of birth technology are mainly focused around issues of "trust and dependence"
      yet there has been no published research to refute or substantiate these beliefs.
      AIM: This paper reports on an empirical study that aimed to identify midwives'
      attitudes to technology usage in the labour ward and specifically the use of the
      cardiotocograph machine (CTG) for electronic foetal monitoring. DESIGN: A postal
      survey was conducted and the questionnaire included a 25-item attitude scale,
      which was designed to assess attitudes towards the use of the CTG machine. All
      midwives (1086) on the United Kingdom Central Council register for Northern
      Ireland were surveyed. The data were factor analysed and compared using several
      categorical groupings including age, perceived skill, prior training with
      computers and trust in the machines. RESULTS: The results indicate that midwives
      reject any notion of them being, or becoming, dependent on machines in their
      practice. However, midwives who trust machines are more disposed to their use and
      trust is affected by perceived competence. CONCLUSION: The paper concludes with a
      recommendation for the future education of midwives to develop and maintain
      competence based craft skills in natural birth as well as high-tech birth.

PMID- 11529961
TI  - Psychiatric nurses' attitudes towards patient autonomy in depot clinics.
AB  - AIM: The aim of this qualitative study was to explore how psychiatric nurses
      experience patient autonomy in relation to their professional role in depot
      clinics. BACKGROUND: The administration of depot neuroleptics at outpatient
      clinics is a common task for psychiatric nurses in many countries. The procedure
      is characterized by brief contacts often allowing little opportunity for adequate
      monitoring of the treatment and a dialog between nurses and patients. As nurses
      have an important role in involving patients in decision-making, there is a need
      to analyse the nurses' attitudes towards giving depot neuroleptics from the
      perspective of autonomy. METHOD: Nine experienced psychiatric nurses were
      interviewed using open-ended questions. The steps of a phenomenological
      descriptive method guided the data analysis. FINDINGS: The structure describes
      how benevolent attitudes towards patient autonomy motivated the nurses'
      interventions in relation to how they experienced their own professional
      authority. The structure consists of four variations: (1) Beneficent
      interventions used with patients perceived as co-operative when the nurses
      experienced a high degree of professional authority. (2) Paternalistic
      interventions used with patients perceived as ambiguous towards medication when
      the nurses experienced an arbitrary professional authority in collaboration with
      team members. (3) Weak paternalistic interventions used with patients perceived
      as unwilling when the nurses experienced having sufficient professional authority
      in the treatment situation. (4) Nonmaleficent interventions used with patients
      perceived as being resigned when the nurses experienced a low degree of
      professional authority within the team. CONCLUSIONS: The findings indicate that
      psychiatric nurses' experience of their professional authority is closely related
      to the organization of the depot treatment and that brief contacts do not favour
      the establishment of collaborative relationships with patients. When injection
      giving nurses, as patients' key workers, have overall responsibility for co
      ordinating the patients' treatment they can encourage patient autonomy by helping
      patients understand the meaning of depot medication and its benefits. Further
      clinical research regarding the involvement of nurses in the treatment as well as
      patients' experiences of treatment with depot neuroleptics is needed to allow
      suggestions about improvements of the organization of the treatment.

PMID- 11529962
TI  - Antecedents to engrossment in Noddings' theory of care.
AB  - BACKGROUND: Nel Noddings theorized caring as a universal social process comprised
      of three phases: engrossment or mental attentiveness, affective engagement or
      empathy and a mental imperative to act on behalf of another. If Noddings' theory
      is correct, caring is a learned process. AIM: The goal of this research was to
      understand the process, particularly engrossment, and to facilitate students'
      development of caring relationships. DESIGN: This qualitative study of 13
      baccalaureate nursing students uncovered six antecedents that facilitated
      student's engrossment and extends Noddings' theory. CONCLUSION: Further research,
      to deepen and synthesize understanding of antecedents and their influence on
      facilitating or inhibiting the caring process, is advocated.

PMID- 11529963
TI  - Hermeneutic notions illuminate cross-cultural nursing experiences.
AB  - AIM OF PAPER: To articulate selected hermeneutic notions for the purpose of
      extending current understanding of cross-cultural nursing practice. BACKGROUND:
      This paper builds upon the findings of a New Zealand project that explored the
      experience of nursing people from cultures other than one's own (Spence 1999).
      The project asserted that the notions of prejudice, paradox and possibility
      portray a nursing view of this phenomenon. ARGUMENT: The discussion is based on
      philosophical hermeneutics as interpreted from the works of Gadamer (1996),
      Taylor (1985a, 1985b, 1995) and Lampert (1997). However the emphasis in this
      paper, rather than being methodological, is on showing how specific hermeneutic
      notions contribute to deeper understanding of the nature of cross-cultural
      practice. It is argued that contact with, and the capacity to explore, the play
      of conflicting prejudices and possibilities enhances understanding of the complex
      and paradoxical nature of cross-cultural nursing.

PMID- 11529964
TI  - The United Kingdom Research Assessment Exercise 2001.

PMID- 11529966
TI  - The occupational profile and associated training needs of the nurse prescriber:
      an empirical study of family planning nurses.
AB  - RATIONALE, AIMS AND OBJECTIVES: The issue of nurse prescribing is highly topical,
      with various United Kingdom Government directives recommending this extension to
      the nursing role. However, despite an imperative to provide 23 000 nurse
      prescribers by March 2001 and to expand this function to half the nursing
      workforce by 2004, there is as yet no agreement as to the occupational profile of
      the nurse prescriber, nor the level and content of any pre-requisite educational
      programme. This study was an attempt to address these unresolved aspects with
      family planning nurses. METHOD: A psychometrically valid and reliable training
      needs analysis instrument was distributed to 1142 family planning nurses, of
      which 388 were returned. This instrument required the respondents to assess 40
      core clinical tasks according to three criteria: how critical each task was both
      to their current role as family planning nurses and to the role of the family
      planning nurse prescriber, and how well each was performed. Comparisons of the
      ratings provided an indicative profile of the role of the family planning nurse
      prescriber and a prioritized list of training needs to achieve this status.
      RESULTS: Generally, and unsurprisingly, the nurse prescribing role was defined
      primarily in terms of prescribing functions, although advanced professional
      issues, communication, teamwork and business/administration were also deemed to
      be salient. Research was not identified as being important. However, with regard
      to the top 15 training needs, seven research tasks were recorded, with the
      remainder including advanced clinical activities, applied pharmacology,
      administration and technical activities. CONCLUSION: This study offers a role
      definition of the nurse prescriber in family planning, and an indicative
      curriculum for cognate educational programmes.

PMID- 11529967
TI  - A synthesis technique for grounded theory data analysis.
AB  - AIMS: The purposes of this paper are to examine the issues surrounding current
      changes in grounded theory (GT) research methods and to explicate an innovative
      synthesis technique to GT data analysis. BACKGROUND: In recent years there has
      been a steady rise in the number of published research reports that use the GT
      method. However, this growing body of GT literature has been criticized for its
      lack of adherence to the method as explicated by its originators, Glaser and
      Strauss. METHODS: Recent and past literature that explicates, describes, and
      discusses GT methods is reviewed. A synthesis technique for grounded theory data
      analysis was developed to analyse qualitative data collected for a grounded
      theory study on caregiving. This synthesis technique was derived from the works
      of four grounded theorists (Kathy Charmaz, Mark Chesler, Juliet Corbin and Anselm
      Strauss). RESULTS: The lack of clarity and the inconsistencies surrounding GT
      analysis, as reported in the literature, resulted in the development of a
      synthesis technique based on the works of the aforementioned-grounded theorists.
      The product was a synthesis approach that included analytical steps from each of
      these authors. CONCLUSIONS: This synthesis approach increased understanding and
      enhanced clarity of GT data analysis techniques. This paper illustrates how
      integration of works by noted qualitative scholars is an appropriate and
      effective means to advance the discourse on data analysis for GT research
      studies.

PMID- 11529968
TI  - Illuminative evaluation: evaluating clinical supervision on its performance
      rather than the applause.
AB  - AIM(S) OF THE PAPER: This paper gives a description of illuminative evaluation
      and argues for its use in process-focused research investigating the reciprocal
      interpersonal interactions between clinical supervisors and their supervisees.
      Experiences from conducting an initial pilot study, which is a part of larger
      qualitative project concerned with individual clinical supervision in mental
      health nursing, are highlighted. BACKGROUND: Research investigating fundamental
      process issues in clinical supervision and their influence on outcomes for
      nursing is uncommon. Previous work in this area has stopped short of exploring
      the supervisory relationship and illuminating the importance of this
      interpersonal process in the delivery of gains. At the heart of the present
      project are questions about which supervisor interventions facilitate and
      constrain the supervisee's use of individual clinical supervision. METHOD: Data
      were collected using individual in-depth interviews, critical incident journals,
      session documents and audio recordings of supervision using illuminative
      evaluation and a case study approach. FINDINGS: Supervisor interventions included
      taking the lead, suggesting an option, exploring the supervisee's work,
      reflecting back, conveying an understanding of client issues, being supportive
      and giving information. Using Heron's framework, catalytic, prescriptive,
      informative and supportive interventions were identified. Interestingly,
      informative interventions related mainly to the sharing of team policy issues and
      were derived from the clinical supervisor's agenda. Although undoubtedly relevant
      to the supervisee's practice, such organizationally focused information giving
      may be at odds with progressing the therapeutic integrity and professional
      development of the supervisee. Degenerative interventions were also illuminated.
      CONCLUSIONS: Following the pilot study, it was concluded that the research
      approach known as illuminative evaluation using multiple case studies is an
      appropriate design to explore the supervisory process and the particular clinical
      supervisor and supervisee interactions which influence this. Potential outcomes
      from the supervisory experience will be contextualized with how mental health
      nurses engage in the supervisory process and the particular supervisor
      interventions delivered during supervision sessions.

PMID- 11529969
TI  - Action research from the inside: issues and challenges in doing action research
      in your own hospital.
AB  - BACKGROUND AND RATIONALE: Nurses are increasingly engaging in action research
      projects to improve aspects of nursing practice, education and management and
      contribute to the development of the profession. Action research involves
      opportunistic planned interventions in real time situations and a study of those
      interventions as they occur, which in turn informs further interventions. Insider
      action research has its own dynamics which distinguish it from an external action
      researcher approach. The nurse-researchers are normally already immersed in the
      organization and have a pre-understanding from being an actor in the processes
      being studied. There is a paucity of literature on the challenges that face nurse
      action researchers on doing action research in their own hospital. AIM: The aim
      of this article is to address this paucity by exploring the nature of the
      challenges which face nurse action researchers. Challenges facing such nurse
      researchers are that they frequently need to combine their action research role
      with their regular organizational roles and this role duality can create the
      potential for role ambiguity and conflict. They need to manage the political
      dynamics which involve balancing the hospital's formal justification of what it
      wants in the project with their own tactical personal justification for the
      project. MAIN ISSUES: Nurse-researchers' pre-understanding, organizational role
      and ability to manage hospital politics play an important role in the political
      process of framing and selecting their action research project. In order that the
      action research project contribute to the organization's learning, nurse action
      researchers engages in interlevel processes engaging individuals, teams, the
      interdepartmental group and the organization in processes of learning and change.
      CONCLUSIONS: Consideration of these challenges enables nurse-action researchers
      to grasp the opportunities such research projects afford for personal learning,
      organizational learning and contribution to knowledge.

PMID- 11529970
TI  - Perceptions of body image, happiness and satisfaction in adolescents wearing a
      Boston brace for scoliosis treatment.
AB  - AIMS: To explore the impact of bracing on the perceptions of body image,
      happiness and satisfaction of adolescents with scoliosis. DESIGN: The study was
      designed as compare of 134 girls and 16 boys who wore a Boston type brace for
      scoliosis treatment and a control group of 99 healthy girls and 51 healthy boys.
      All them were secondary school pupils living in Athens Greece and were
      interviewed. A semi-structured schedule included general questions, and the Piers
      Harris scale was used. Data were analysed using the SPSS/PC+ software, and
      descriptive statistics, factor analysis and the non-parametric Mann-Whitney U
      test. Statistical significance was set at P=0.05 or less. RESULTS: The scoliosis
      group had a poorer perception of body image in comparison to the control group
      (P=0.048), while boys with scoliosis (P=0.030) had a better perception of body
      image than girls with scoliosis. Girls with scoliosis had a statistically
      significant difference (P=0.0388) in perception of happiness and satisfaction, in
      comparison with girls in the control group. Cohabitation with the mother seemed
      to be negatively correlated with body image, happiness and satisfaction
      perceptions because adolescents with scoliosis who were not living with their
      mother had a better body image perception (P=0.027) as well as better perceptions
      of happiness and satisfaction (P=0.047). Nevertheless, only 5% of those with
      scoliosis declared that they had opportunities to discuss their feelings and
      problems with health professionals, while 90% of them declared that they wanted
      to have more opportunities to do this. CONCLUSION: Adolescents with scoliosis
      face problems during bracing and they need to be supported by health care
      professionals.

PMID- 11529971
TI  - Psychosocial correlates of fluid compliance among Chinese haemodialysis patients.
AB  - AIMS: The present study was designed to determine the psychosocial correlates of
      fluid compliance among patients receiving haemodialysis at two Hong Kong renal
      dialysis centres. BACKGROUND: There has been little consistency in the findings
      of correlations among any psychosocial variables and compliance behaviour. There
      is a need to further study these variables in an attempt to predict haemodialysis
      patient compliance to fluid restriction. METHODS: Ninety-two Chinese
      haemodialysis patients completed the Center for Epidemiological Studies
      Depression Scale (CES-D), The Multidimensional Health Locus of Control Form C
      Scale (MHLC), the Social Support Questionnaire, Short Form Scale (SSQ6) and a
      self-designed socio-demographic questionnaire. Daily interdialytic weight gain
      (DIWG) measure was used as an indicator of fluid compliance. RESULTS: The
      prevalence of compliance behaviour of Chinese haemodialysis patients was higher
      than that reported in western studies. There were significant negative
      correlations found between DIWG and total score on internal health locus of
      control and social support satisfaction score. However, internal health locus of
      control did not predict a significant portion of the DIWG variance. Significant
      predictors of DIWG included satisfaction with social support, comorbidity and
      monthly family income. Satisfaction with social support was the largest predictor
      of DIWG. CONCLUSIONS: The present findings suggest that assessing family income,
      comorbidity, and satisfaction with social support may be useful in identifying
      haemodialysis patients potentially at risk for difficulties in compliance with
      fluid restriction.

PMID- 11529972
TI  - HeartCare: an Internet-based information and support system for patient home
      recovery after coronary artery bypass graft (CABG) surgery.
AB  - HeartCare is an Internet-based information and support service for patients
      recovering at home from coronary artery bypass graft (CABG) surgery. The system
      is designed to meet the nursing challenges in health information to support needs
      of CABG patients. HeartCare (a) provides information and support, tailored to
      patients' individual and changing recovery needs during CABG recovery, (b) makes
      recovery information more accessible for timely use by patients, and (c) extends
      the scope of nursing services to CABG patients from hospital through home. An
      ongoing randomized controlled study is underway to evaluate the clinical outcomes
      of patients' use of the HeartCare system and to examine its acceptance as a
      usable resource for postCABG patients who have limited previous computer
      experience.

PMID- 11529973
TI  - Timing of quality of life (QoL) assessments as a source of error in oncological
      trials.
AB  - AIM OF THE STUDY: To produce an empirical estimate of the nature and magnitude of
      the error produced by incorrect timing quality of life (QoL) measurements in
      patients receiving chemotherapy. DESIGN: In a multicentre trial, 283 patients
      were randomized to receive either docetaxel (T) or sequential methotrexate and 5
      fluorouracil (MF). The QoL was assessed at baseline and before each treatment
      using the European Organization for Research and Treatment of Cancer Quality of
      Life Questionnaire (EORTC QLQ-C30). The study design was retrospective. Data were
      analysed using t-tests. RESULTS: Erroneous timing affected the QoL findings in
      both treatment arms. At baseline, there were statistically significant
      differences in the MF group on the nausea/vomiting scale, with ill-timed
      assessment showing more symptoms, and in the T group on the physical functioning
      scale with ill-timed assessments indicating better QoL. The mean scores of
      correct vs. incorrect timings over the first 14 cycles showed statistically
      significant differences on several scales. In the MF group, ill-timed assessments
      indicated significantly worse physical functioning and global QoL, and
      significantly more of the following symptoms: fatigue, nausea/vomiting, insomnia,
      appetite loss, and constipation. In the T group, ill-timed assessment showed
      better physical functioning, less dyspnoea and more insomnia than correctly timed
      assessments. The reasons for erroneous timing were not always detectable
      retrospectively. However, in some cases the MF group, being in standard
      treatment, seemed to have followed a clinical routine not involving the active
      participation of the study nurse responsible, whereas patients in the
      experimental T group were more consistently taken care of by the study nurses.
      CONCLUSIONS: Incorrect timing of QoL assessments in oncological trials
      jeopardises both the reliability of the QoL findings within treatment and the
      validity of QoL outcome comparisons between treatments. This issue should be
      emphasized in the planning of both the study design and clinical routines.

PMID- 11529974
TI  - Being overwhelmed by the feeling of having a home and family. One aspect of the
      meaning of being dependent on care: a study of one patient and two of his nurses.
AB  - RATIONALE: This article is part of an ongoing study which aims at disclosing the
      meaning of being dependent on care. From a larger body of data, interviews with
      one patient and two of his nurses were selected to study. AIM: The aim was to
      deepen understanding of the meaning of being dependent on care when this appears
      desirable for the patient. METHODS: A phenomenological-hermeneutic approach was
      used to interpret the material. Interviews were recorded and transcribed
      verbatim. FINDINGS/DISCUSSION: The interpretation discloses the meaning of being
      dependent on care as an overwhelming, unfamiliar feeling of having a home and
      family. The patient is beguiled into believing he is the ruler in an established
      relationship and his dependency on care gives him an opportunity to be surrounded
      by loving, altruistic, helpful people. Being dependent on care is overwhelming
      and irresistible, i.e. coveted, but simultaneously it is like walking on thin
      ice, i.e. treacherous. The irresistible desire concerns being unconditionally
      cared about. The danger is that this 'family membership' will not last. It is
      brought to the patient because of his dependency on care and it is based on his
      terms. There is reflection about the patient being unprepared for dealing with
      his own world of loneliness.

PMID- 11529975
TI  - The quality of nursing home care: do the opinions of family members change after
      implementation of emotion-oriented care?
AB  - OBJECTIVE: The present study focuses on opinions on the quality of nursing home
      care of family members of nursing home residents with dementia. Furthermore, we
      examined whether family members' appreciation of the care increased as a result
      of the implementation of emotion-oriented care. DESIGN: Randomized clinical
      trial. INSTRUMENT: An 18-item questionnaire was developed. The following subjects
      were addressed: communication activities between staff and family members;
      satisfaction regarding contacts with staff; the extent to which family members
      can participate in care; the contact that family members experience with the
      person with dementia, and opinions about the way in which nursing staff treat
      residents. RESULTS: Most family members already had a positive opinion on the
      nursing home care prior to the implementation of emotion-oriented care. The most
      positive assessment concerned the way in which nursing staff treated residents.
      The lowest scores concerned communication activities between ward staff and
      family members. Comparison of the first and end measurements showed that in
      general opinions on the quality of care did not change. STUDY LIMITATIONS: A
      large number of incomplete questionnaires made it impossible to conduct factor
      analysis on the classification of the questions in various sections and therefore
      allowed us only to make statements at the item level. CONCLUSIONS: For the most
      part family members had a positive opinion on the nursing home care. In general,
      implementation of emotion-oriented care did not lead to a more positive
      assessment. Despite the generally accepted notion that involving family members
      in care is important, family members were regularly treated as outsiders. This
      demonstrates that there is room for improvement in the communication by nursing
      home staff with family members (e.g. more frequent contacts and information about
      the illness).

PMID- 11529976
TI  - The relationship of a mother's working model of feeding to her feeding behaviour.
AB  - AIMS OF THE STUDY: This study aimed to examine the difference the attunement of a
      mother's working model of feeding to her infant makes for her positive feeding
      affect and behaviour, accounting for infant and mother conditions.
      BACKGROUND/RATIONALE: The concept of a mother's working model of feeding is
      derived from attachment theory. Caregiving, including feeding, is a component of
      this theory. The conditions that may influence the attunement of a mother's
      working model of feeding to her infant include infant birth maturity status
      (premature, full-term), age at assessment, and robustness, indexed by weight-for
      age z score (WAZ). Mother conditions include symptoms of depression and feeding
      practice (breast feeding or exclusive bottle feeding). DESIGN/METHODS:
      Participants in this longitudinal study were 99 mothers and their infants (47
      full-term, 52 premature, very low birth weight). After written informed consent
      was given, home assessments were made when infants were approximately 1, 4, 8 and
      12 months old (adjusted age for premature infants). Working model attunement was
      assessed with a video-assisted interview. A mother's positive affect and
      behaviour, including sensitivity and responsiveness, were rated from videotaped
      feeding interaction. RESULTS/FINDINGS: Repeated measures analysis with a general
      linear mixed model showed a significant positive relationship with positive
      affect and behaviour for both working model attunement and the WAZ score and a
      significant negative relationship for symptoms of depression. Neither birth
      maturity status, infant age, nor feeding practice had a significant effect on
      mother's positive affect and behaviour during feeding. CONCLUSIONS: Nurses'
      efforts to enhance the attunement of a mother's working model of feeding may help
      mothers feed with greater positive affect and behaviour. Further study of how the
      attunement of a mother's feeding expectations and intentions are related to her
      symptoms of depression and with what she makes of the infant's growth and well
      being is needed. The theoretical model needs testing with infants from the entire
      premature population.

PMID- 11529978
TI  - Healing through self-reflection.
AB  - BACKGROUND: Today, women have an enlightened view towards their life cycles,
      which is evidence of their healing potential. Women need to share their insights
      about their healing potential gained through self-reflective processes. Their
      voices must be heard so that we can benefit from their collective wisdom. The
      process of healing through self-reflection has begun as a group of nurses share
      their insights. Documenting the perspectives of these nurses provides the
      opportunity for other women to learn from and apply this knowledge to their
      lives. METHOD: Through purposive sampling, eight registered nurses, all women,
      were selected to participate in in-depth, personal, semi-structured interviews.
      The purposes in this paper are to describe a three-stage (i.e. awareness,
      critical analysis, and new perspective) reflective-thinking model and discuss the
      application of this model to women's expressed inner knowledge and wisdom across
      personal and professional life cycles. RESULTS: Three themes, signifying their
      ability to heal themselves, were labelled: Spirituality, Be-ing Versus Do-ing,
      and Eustress Versus Distress. CONCLUSIONS: Essentially, self-reflection results
      from both personal and professional stimuli and signifies the need for change so
      that healing can begin. Recommendations are offered for nurse educators and
      researchers.

PMID- 11529977
TI  - Comparison of caloric intake and weight outcomes of an ad lib feeding regimen for
      preterm infants in two nurseries.
AB  - BACKGROUND: Effects on caloric intake and weight gain of an ad libitum (ad lib)
      feeding regimen for preterm infants may be specific to a special care nursery.
      OBJECTIVE: To explore across two nurseries the similarity of effect on caloric
      intake and weight gain of an ad lib feeding regimen compared with a prescribed
      regimen and the similarity of effect of caloric intake on weight gain. METHODS:
      All infants participating in the multi-site randomized clinical trial (RCT) of
      the ad lib feeding regimen were <35 weeks gestational age at birth and had birth
      weight appropriate for gestational age. Data on caloric intake and weight gain
      were collected at two nurseries (A, n=22; B, n=78) with the same feeding regimen
      protocols. Two strategies were used to explore similarity of regimen effect on
      caloric intake and weight gain. Repeated measures analysis of variance (ANOVA)
      was used to examine the effect on caloric intake and weight gain of time, feeding
      regimen, and time-by-regimen interaction for each nursery. RESULTS: In both
      nurseries, regimen effects were reasonably consistent for caloric intake and
      weight gain. Caloric intake was lower across nurseries for infants fed ad lib.
      After accounting for caloric intake, the ad lib regimen did not affect weight
      gain. The time-by-regimen interaction effect on caloric intake was significant in
      both nurseries. Caloric intake for infants fed ad lib increased significantly
      over 5 days. CONCLUSIONS: Despite differences between nurseries in infant
      characteristics and in protocol implementation, the feeding regimen effect was
      consistent for caloric intake and weight gain. Further support was found for the
      development of infant self-regulatory capacity.

PMID- 11529979
TI  - Qualified nurses' smoking prevalence: their reasons for smoking and desire to
      quit.
AB  - AIM AND RATIONALE: The preventable nature of smoking related diseases places a
      major responsibility for health promotion on all health professionals. This study
      used a questionnaire to survey qualified nurses in Northern Ireland as to smoking
      prevalence and their desire to quit the habit. It also explores their knowledge
      base relating to smoking related diseases and their motivation to act as health
      promoters with patients who smoke. METHODS: A random sample (n=1074) of qualified
      nurses employed by the Health and Social Services Trusts, private, and voluntary
      organizations in the province were surveyed. RESULTS: Results show that 25.8%
      were smokers, 19% were ex-smokers and 55.2% were nonsmokers. Three quarters
      expressed a wish to stop within 6-months. Almost all smokers and half of ex
      smokers had taken up the habit prior to commencing nursing. 'Addiction' and
      'enjoyment' were given as the principle reasons for continued smoking. Health
      reasons were paramount in smokers' desire to stop smoking. CONCLUSIONS: These
      findings suggest that smoking prevalence among qualified nurses in no greater
      than that reported by females in the general Northern Ireland population. Results
      also indicate that those nurses who smoke were less willing to take on the role
      of a health promoter with patients who smoke. Implications and recommendations
      for practice, education and research are explored.

PMID- 11529980
TI  - Using a management perspective to define and measure changes in nursing
      technology.
AB  - AIMS: The aims of this paper are to discuss the uses of the concept of technology
      from the medical science and the management perspectives; to propose a clear
      definition of nursing technology; and to present a study applying the use of the
      concept of nursing technology on nursing units. BACKGROUND: Nurse managers must
      use management terms correctly and the term technology may be misleading for
      some. A review of the nursing literature shows varied uses of the concept of
      technology. Thus a discussion of the dimensions, attributes, consequences, and
      definitions of nursing technology from the management perspective are given.
      DESIGN: A longitudinal study to measure the dimensions of nursing technology on
      nursing units 10 years apart. RESULTS: The findings suggest that the dimensions
      of nursing technology change over time and support the need for nurse managers to
      periodically assess nursing technology before making management changes at the
      level of the nursing unit. CONCLUSIONS: This study helps health care providers
      understand the unique role of nurses as healthcare professionals by identifying
      and measuring nursing technology on the nursing unit.

PMID- 11529981
TI  - Nursing staff members' intentions to use physical restraints with older people:
      testing the theory of reasoned action.
AB  - AIM OF THE STUDY: To examine nursing staff members' attitudes, subjective norms,
      moral obligations and intentions to use physical restraints, using the Theory of
      Reasoned Action (TRA). RATIONALE: During the last two decades an extensive body
      of research has examined nurses' attitudes as one of the main factors affecting
      the decision to use or not to use physical restraints with older persons.
      However, no studies have examined empirically the antecedents to nurses'
      intentions to use physical restraints within a theoretically based framework.
      METHOD: A correlational design was used with 303 nursing staff members from an
      800-bed elder care hospital in central Israel. Participants completed a
      questionnaire including questions based on the TRA as well as socio-demographic
      and professional characteristics. RESULTS: Regression analyses found attitudes,
      subjective norms and moral considerations to be significantly associated to
      intention to use physical restraints with older people. The TRA explained 48% of
      the variance in nurses' intentions. CONCLUSIONS: The TRA proved to be a useful
      framework for examining nurses' intentions to use physical restraints. Nurses'
      attitudes, beliefs and expectations of significant others should be examined
      before implementing educational programmes regarding the use of physical
      restraints.

PMID- 11529982
TI  - HIV, stigma and health: integration of theoretical concepts and the lived
      experiences of individuals.
AB  - AIM: To explore individual concepts of health and the role of stigma in human
      immunodeficiency virus (HIV) and HIV disease. The balance of power and knowledge
      are examined from both macro and micro perspectives, including both concepts of
      health and health and illness behaviour. METHOD: A literature review which
      supports the integration of theoretical concepts and research findings
      demonstrating the lived experiences of individuals. CONCLUSION: Stigma is a
      social construct which has significant impact on the life experiences of
      individuals both infected with and affected by HIV. The stigma experienced is
      unique to each individual and changes dynamically throughout the course of the
      HIV illness trajectory. Each of the four identified phases poses unique stigmatic
      qualities.

PMID- 11529983
TI  - Rationing scarce life-sustaining resources on the basis of age.
AB  - AIMS: The aim of this paper is to analyse critically the use of age as a
      criterion to ration scarce life-sustaining resources within the intensive care
      environment. BACKGROUND: Insufficient funding to meet the escalating costs of
      health care has resulted in a scarcity of life-sustaining resources. Although an
      explicit policy of rationing by age within the United Kingdom (UK) has not been
      formulated, decisions to withhold or withdraw treatment are already being made on
      the basis of patients' biological age rather than medical need. METHOD: Three
      contrasting arguments are analysed: the 'equal worth', 'fair innings' and
      'prudential lifespan' arguments. CONCLUSIONS: In certain circumstances rationing
      by age is both morally permissible and justified. However, the capacity to
      benefit from treatment has to be considered whatever the age of the individual
      and any measure of benefit needs to take a broad range of medical, ethical and
      economic factors into account. If age is to be used, as a criterion to ration
      limited resources explicit, national guidelines need to be developed and applied
      consistently to ensure that arbitrary differences in the treatment older people
      receive does not occur.

PMID- 11529984
TI  - Fetal imaging in a new era.

PMID- 11529985
TI  - Placenta previa and vasa previa: time to leave the Dark Ages.

PMID- 11529986
TI  - Diagnosis of low-lying placenta: can migration in the third trimester predict
      outcome?
AB  - OBJECTIVES: To investigate the relationship between the rate of migration of a
      low-lying placenta during the third trimester and the eventual route of delivery.
      METHODS: All patients with a placenta lying within 3 cm of the internal cervical
      os or overlapping it on transvaginal ultrasound at > or = 26 weeks' gestation
      were included in the study. The exact distance between the center of the internal
      cervical os and the leading edge of the placenta was measured by transvaginal
      sonography, repeated at approximately 4-week intervals until delivery. RESULTS:
      The mean rates of migration in patients who had (n = 7) and who did not have (n =
      29) Cesarean section for placenta previa were +0.3 mm/week and +5.4 mm/week,
      respectively (P < 0.0001). When the placental edge was initially > 20 mm from the
      internal os, migration occurred in all cases and no Cesarean section for placenta
      previa was performed. For those between -20 mm and +20 mm, sufficient migration
      to avoid Cesarean section occurred in 88.5% of cases. Beyond a 20 mm overlap,
      significant placental migration did not occur and all patients required Cesarean
      section. CONCLUSION: Placental migration may occur progressively throughout the
      third trimester. The initial position of the placental edge and the subsequent
      rate of migration can be used to predict the eventual route of delivery.

PMID- 11529987
TI  - Third-trimester transvaginal ultrasonography in placenta previa: does the shape
      of the lower placental edge predict clinical outcome?
AB  - OBJECTIVE: To evaluate the clinical significance of the shape of the lower
      placental edge in women with transvaginal sonographic diagnosis of placenta
      previa. DESIGN: A prospective observational study at a tertiary teaching
      hospital. POPULATION: A total of 104 women with confirmed transvaginal
      sonographic diagnosis of placenta previa before 32 weeks' gestation. METHODS:
      Initial transvaginal sonography was performed at between 28 and 32 weeks'
      gestation in 138 patients with either strong clinical suspicion or previous
      abdominal sonographic diagnosis of placenta previa in the early third trimester.
      The lower placental edge was found to be positioned over the internal cervical os
      in 33 women (complete previa) and within 3 cm from it in 71 women (low-lying
      placenta). Patients with low-lying placenta were followed up by serial
      transvaginal sonographic examinations until delivery; detailed information
      including the placental location (anterior or posterior), the distance of its
      edge from the internal cervical os and its thickness were recorded. The clinical
      outcomes of the 17 who had a thick-edge low-lying placenta were compared with
      those who had a thin-edge one (54 women). In patients with complete placenta
      previa, demographic data, the shape of the lower placental edge whenever
      transvaginal sonography visualized it, and the clinical outcomes were documented.
      The incidence of major complications in thick-edge or central placenta was
      compared to that in the thin-edge group. RESULTS: Women having a low-lying
      placenta with a thick edge had a significantly higher rate of antepartum
      hemorrhage (P = 0.0002), abdominal delivery (P = 0.02), abnormally adherent
      placenta (P = 0.012) and low birth weight (P = 0.006) than those in whom the
      placental edge was thin. Cesarean hysterectomy was required in six patients with
      complete placenta previa because of severe peripartum hemorrhage; all of them had
      either central or thick-edge placenta accreta. CONCLUSION: Women with placenta
      previa are at a relatively higher risk of developing complications if the lower
      placental edge is thick. Integration of the shape of the lower placental edge
      into transvaginal sonographic assessment of placenta previa may improve the
      prediction of mode of delivery and clinical outcome.

PMID- 11529988
TI  - Prenatal sonographic diagnosis of vasa previa: ultrasound findings and obstetric
      outcome in ten cases.
AB  - OBJECTIVE: To assess the specificity of sonographic diagnosis of vasa previa and
      pregnancy outcome in sonographically diagnosed cases. METHODS: We prospectively
      collected cases of vasa previa diagnosed by color Doppler sonography. Delivery by
      elective Cesarean section after demonstration of fetal pulmonary maturity and
      prior to the onset of labor was recommended unless obstetric complications
      supervened. Data regarding maternal obstetric courses and newborn status were
      collected. RESULTS: Eleven cases of vasa previa without placenta previa were
      diagnosed among 33 208 women over an 8-year period. Ten patients had confirmation
      of the diagnosis by the delivering obstetrician and/or placental examination,
      giving a specificity of diagnosis of 91%. Among the 10 patients with confirmed
      vasa previa, two were delivered at 31.5 and 35.5 weeks' gestation prior to
      demonstration of lung maturity, and the remainder were delivered at 34-37.5
      weeks, after lung maturity. All infants had normal Apgar scores and survived. One
      baby had Scimitar syndrome, which was not suspected from sonography. CONCLUSIONS:
      The specificity of sonographic diagnosis of vasa previa at our center was 91%.
      Antenatal diagnosis permitted us to prevent the catastrophic outcomes commonly
      associated with vasa previa.

PMID- 11529989
TI  - Three-dimensional sonographic volumetry of the placenta and the fetus between
      weeks 15 and 17 of gestation.
AB  - OBJECTIVES: Three-dimensional sonographic volume measurement enables for the
      first time direct comparison of the increase in size of different but closely
      interacting structures like the placenta and fetus. Our aim was to calculate the
      fetal and placental volumes between weeks 15 and 17 of gestation, to monitor the
      difference in the increase of the fetal and placental sizes and to determine
      their mutual relationship. METHODS: Fetal and placental sonographic volume
      measurements were made in 356 singleton pregnancies. To measure the relationship
      between fetal and placental volumes, a quotient was calculated. Regression
      analyses were performed to analyze the dependence of the fetal and placental
      volumes and placental quotient on the week of gestation and other influencing
      variables. RESULTS: The mean of the fetal volume increased markedly from 67.8 to
      76.6 mL (by 13%) within the 3 weeks of observation, whereas placental volume
      increased only slightly (111.1 to 114 mL (by 2.6%)). The random variation of
      placental volumes around the mean in all three gestational weeks was considerably
      higher than that of fetal volumes, indicating that in this early period of
      gestation there is little correlation between fetal and placental sizes. Fetal
      volume correlated better to gestational week than did placental volume.
      CONCLUSION: The quotient of fetal and placental volume might assist in the
      diagnosis of high-risk pregnancies and the assessment of a normal or large fetus
      with a small placenta.

PMID- 11529990
TI  - Nomogram of Wharton's jelly as depicted in the sonographic cross section of the
      umbilical cord.
AB  - OBJECTIVES: To generate a nomogram for the sonographic measurement of Wharton's
      jelly area (WJA) during gestation and to investigate whether WJA is related to
      fetal biometric parameters. METHOD: The sonographic cross-sectional area of the
      umbilical cord and of its vessels was measured in 659 fetuses between 15 and 42
      weeks of gestation. The WJA was calculated by subtracting the vascular area from
      the umbilical cord area. The conventional biometric parameters were measured and
      correlated with the WJA. Polynomial regression analysis was utilized for
      statistical purposes. RESULTS: The WJA increased as a function of gestational age
      (r = 0.63, P < 0.001). The regression equation for the mean WJA (y) according to
      gestational age (x) was y = -114.7 + 4.142x - 0.01x2 and for the standard
      deviation (y') was y' = -7.567 + 1.319x. There was a strong correlation between
      the WJA and the umbilical cord area (r = 0.97, P < 0.001). A significant
      correlation was also found between the WJA and fetal biometric parameters before
      32 weeks of gestation (WJA and biparietal diameter: r = 0.82, P < 0.001; WJA and
      abdominal circumference: r = 0.79, P < 0.001; WJA and femur length: r = 0.81, P <
      0.001) while after 32 weeks of gestation no correlations were found between WJA
      and fetal anthropometric parameters. CONCLUSION: A nomogram for the WJA has been
      generated. The WJA increases as a function of gestational age and it is
      correlated with fetal size up to 32 weeks of gestation.

PMID- 11529991
TI  - Isolated echogenic foci in the fetal heart: do they increase the risk of trisomy
      21 in a population previously screened by nuchal translucency?
AB  - OBJECTIVES: To confirm the hypothesis that isolated cardiac echogenic foci at the
      second-trimester anomaly scan do not influence our current calculation of risk of
      trisomy 21 in individual pregnancies, which is based on maternal age and nuchal
      translucency thickness at 11-14 weeks. DESIGN: Observational study in a fetal
      medicine unit. METHODS: In a general pregnant population undergoing first
      trimester nuchal translucency screening, data from 239 singleton pregnancies with
      isolated cardiac echogenic foci at the second-trimester anomaly scan were
      compared with those of a control group of 7449 pregnancies with normal anomaly
      scans. Prevalence of trisomy 21 was determined in both groups. Following the
      anomaly scan, the individual risks of trisomy 21 were calculated by adjusting the
      previous risk based on maternal age and first-trimester nuchal translucency. We
      assumed that echogenic foci did not alter each individual risk calculation. The
      expected number of cases of Down syndrome in both groups was then calculated from
      the sum of probabilities of each individual affected fetus. The observed number
      of cases was compared with the expected number in both study and control
      populations. RESULTS: There was no statistically significant difference between
      the prevalence of trisomy 21 in the study group (no cases) and in the control
      population (three cases). From individual risk calculations, observing no cases
      of trisomy 21 in the study group was the most likely event if echogenic foci did
      not increase the risk of this chromosomal abnormality (P = 0.62). CONCLUSION: The
      finding of isolated echogenic foci at the time of the 20 week-scan does not
      significantly change the risks of trisomy 21 if background risk and previous
      nuchal translucency measurements are taken into account in the individual risk
      calculation. We suggest that no further adjustments to risk should be used.

PMID- 11529992
TI  - Cardiac function in fetuses with intracardiac echogenic foci.
AB  - OBJECTIVE: To evaluate cardiac dimensions and function in euploid fetuses with
      intracardiac echogenic foci. STUDY DESIGN: Forty-eight fetuses with a single
      cardiac echogenic focus situated in the left ventricle had echocardiography
      performed at 22-24 weeks of gestation. Fifty normal fetuses at 22-24 weeks'
      gestation served as controls. Two-dimensional and M-mode directed fetal
      echocardiography were used to exclude cardiac anomalies and measure right and
      left ventricular free walls and interventricular septal thickness and ventricular
      systolic and diastolic dimensions. Cardiac size was expressed as a ratio of
      ventricular wall thickness/biparietal diameter, and cardiac function was
      expressed as ventricular shortening fraction. Doppler fetal echocardiography
      measurements included pulmonary and aortic maximum systolic velocities and time
      to peak velocities as indices of ventricular systolic function, and the ratio
      between early ventricular filling (E-wave) and active atrial filling (A-wave)
      peak velocities at the level of the atrioventricular valves as an index of
      ventricular diastolic function. RESULTS: Early ventricular filling/active atrial
      filling peak velocity ratios were significantly lower in fetuses with
      intracardiac echogenic foci than in control fetuses. In the mitral valve the
      ratio was 0.37 +/- 0.14 (0.039) (mean +/- SD (95% confidence interval for
      difference between the means)) vs. 0.59 +/- 0.19 (0.052) and in the tricuspid
      valve it was 0.42 +/- 0.16 (0.045) vs. 0.62 +/- 0.21 (0.058). No significant
      differences were found in cardiac dimensions, ventricular shortening fraction and
      Doppler systolic indices. CONCLUSION: Euploid fetuses with intracardiac echogenic
      foci show low E/A ratio values in midtrimester echocardiography. This finding
      might indicate cardiac diastolic dysfunction.

PMID- 11529993
TI  - Fetal heart rate and umbilical artery velocity variability in fetuses with
      congenital cardiac defects: a preliminary study.
AB  - OBJECTIVE: To examine whether variabilities in fetal heart rate and umbilical
      artery flow velocity are possible markers for hemodynamic dysfunction in fetuses
      with a congenital heart defect. METHODS: Doppler studies of the umbilical artery
      velocity waveform were performed at 20-35 weeks of gestation in 13 patients with
      a congenital heart defect. We determined absolute and variability values for
      heart rate and flow velocities from umbilical artery velocity waveforms of at
      least 18 s duration. We compared these findings with normal controls matched for
      gestational age. RESULTS: Fetuses with a congenital heart defect displayed
      decreased umbilical artery peak systolic and time-averaged velocities. However,
      variability in peak systolic and time-averaged velocities and fetal heart rate
      variability were increased compared with normal controls. Absolute fetal heart
      rates were similar between the two groups. CONCLUSIONS: Marked cardiovascular
      changes occur in the fetus with a congenital heart defect compared with the
      normal healthy fetus. We propose that variability in fetal heart rate and
      umbilical artery blood flow velocity could be additional markers for impaired
      homeostasis in the presence of fetal congenital heart disease.

PMID- 11529994
TI  - Doppler studies on the fetal renal artery in the severely growth-restricted
      fetus.
AB  - OBJECTIVES: To examine changes with time in the fetal renal circulation by
      Doppler sonography in the severely growth-restricted preterm fetus during the
      period of gradual deterioration prior to delivery, and to examine the
      relationship between Doppler measurements, amniotic fluid index, birth weight and
      fetal condition at birth. METHODS: This was a prospective observational study in
      16 preterm growth-restricted fetuses between 26 and 35 weeks of gestational age.
      Serial Doppler measurements were made of the renal artery, umbilical artery,
      middle cerebral artery and ductus venosus. RESULTS: The pulsatility index in the
      renal artery did not show any correlation with cord blood pH, birth weight or
      amniotic fluid index corrected for gestational age (Delta/SDAFI). However, peak
      systolic velocities in the renal artery showed a significant reduction with time
      (n = 7, P < 0.05) and a significant correlation with: venous cord pH at delivery
      (n = 12, r = 0.84, P < 0.001), Delta/SDAFI (n = 16, r = 0.67, P < 0.01), and
      birth weight (n = 16, r = 0.61, P < 0.02). Birth weight correlated significantly
      with: Delta/SDAFI (n = 15, r = 0.57, P < 0.05), pulsatility index values of the
      middle cerebral artery (n = 15, r = -0.61, P < 0.02), and pulsatility index
      values of the ductus venosus (n = 16, r = 0.55, P < 0.05), and Delta/SDAFI
      correlated significantly with: pulsatility index values of the ductus venosus (n
      = 15, r = 0.51, P < 0.05) and arterial cord pH values at delivery (n = 8, r =
      0.78, P < 0.05). CONCLUSIONS: Progressive redistribution of the circulation
      occurs with deterioration of the fetal condition in the growth-restricted preterm
      fetus. On spectral Doppler this is reflected by changes in peak systolic
      velocities, but not by changes in pulsatility values of the fetal renal artery
      waveforms.

PMID- 11529995
TI  - The clivus-supraocciput angle: a useful measurement to evaluate the shape and
      size of the fetal posterior fossa and to diagnose Chiari II malformation.
AB  - OBJECTIVE: To obtain a nomogram of the clivus-supraocciput angle as a basis for
      the diagnosis of Chiari II malformation in fetuses with ventriculomegaly.
      METHODS: A cross-sectional study was undertaken on 310 normal pregnant women of
      16-34 weeks' gestation. A mid-sagittal section of the fetal skull was obtained
      and the angle between the clivus and the supraocciput was measured. Forty-four
      fetuses with ventriculomegaly due to various causes (13 Chiari II malformation,
      12 dysgenesis of the corpus callosum, 7 aqueductal stenosis, 6 borderline
      ventriculomegaly, 3 Dandy-Walker malformation, 2 porencephaly, 1 schizencephaly)
      were also included in the study and the values of the angle found in the
      pathological cases were compared with those found in the normal population.
      RESULTS: The clivus-supraocciput angle did not change during gestation and was
      almost constant with an average value of 79.3 +/- 6 degrees. All cases of Chiari
      II malformation showed a value below the 5th centile of our nomogram.
      CONCLUSIONS: The evaluation of the posterior fossa and particularly the
      measurement of the clivus-supraocciput angle is a useful parameter to
      differentiate the various causes of fetal ventriculomegaly and particularly to
      recognize Chiari II malformation.

PMID- 11529996
TI  - Fetal iliac angle measurements by three-dimensional sonography.
AB  - OBJECTIVE: To determine the technical reliability of fetal iliac angle
      measurements by three-dimensional sonography as a prenatal marker for Down
      syndrome. METHODS: Three-dimensional multiplanar views of the fetal pelvis were
      used to standardize iliac angle measurements from 35 normal second-trimester
      pregnancies. Measurement reliability for a single examiner and between two
      different examiners were analyzed by intraclass correlation. Normal iliac angle
      measurements were compared to those obtained from 16 fetuses with trisomy 21.
      RESULTS: The mean axial angle for normal fetuses was 79 +/- 5.5 degrees, which
      was significantly less than that observed in fetuses with trisomy 21 (87.7 +/-
      4.9 degrees ) (P < 0.001). Iliac angles did not correlate with gestational age.
      Axial angles were reproducible between two examiners who measured the same
      multiplanar view of the pelvis. Inter- and intraobserver reliability were also
      acceptable after a standardized multiplanar view was independently obtained by
      each examiner (intraclass correlation = 0.91 for both). Coronal angles were
      unreliable because of difficulties with finding a reproducible measurement plane.
      For a false-positive rate of 5%, an axial angle threshold of 87 degrees correctly
      identified 56% of fetuses with trisomy 21. CONCLUSION: Axial iliac angle
      measurements are reliable by standardized three-dimensional multiplanar views of
      the pelvis and can be used to identify some fetuses at increased risk for trisomy
      21.

PMID- 11529997
TI  - Cerebral lateral ventricular atrial diameter of male and female fetuses at 20-24
      weeks' gestation.
AB  - OBJECTIVE: To determine if the lateral ventricular atrial diameter differs
      between male and female fetuses at 20-24 weeks' gestation. DESIGN: Prospective
      study. METHODS: The transverse diameter of the ventricular atrium was measured
      from inner wall to inner wall for a total of 202 pregnant women with 105 male
      fetuses and 97 female fetuses. RESULTS: The mean diameter of the ventricular
      atrium for the 202 fetuses was 4.96 +/- 0.96 mm (range, 2.1-8.4 mm). The 105
      males had a mean diameter of 4.95 +/- 0.98 mm and the 97 females a mean diameter
      of 4.97 +/- 0.94 mm. There was no statistical difference between the sexes.
      CONCLUSIONS: In our population, there was no difference between ventricular
      atrial diameter in male and female fetuses at 20-24 weeks' gestation.

PMID- 11529998
TI  - Transvaginal sonography, saline contrast sonohysterography and hysteroscopy for
      the investigation of women with postmenopausal bleeding and endometrium > 5 mm.
AB  - OBJECTIVES: To determine the ability of transvaginal ultrasound, with or without
      saline infusion, to detect focally growing lesions in the uterine cavity in women
      with postmenopausal bleeding and endometrium > 5 mm, and to determine the
      accuracy of conventional ultrasound, saline contrast sonohysterography and
      diagnostic hysteroscopy under general anesthesia to diagnose endometrial polyps,
      submucous myomas and uterine malignancy. DESIGN: In a prospective study, 105
      women with postmenopausal bleeding and endometrium > 5 mm underwent conventional
      ultrasound examination and saline contrast sonohysterography. Diagnostic and
      operative hysteroscopy under general anesthesia was then performed. The presence
      of focally growing lesions and the type of lesion (endometrial polyp, submucous
      myoma, malignancy or unclear focal lesion) were noted at ultrasound examination
      and at hysteroscopy. RESULTS: There was almost perfect agreement (96%) between
      saline contrast sonohysterography and hysteroscopy in the diagnosis of focally
      growing lesions. Saline contrast sonohysterography and hysteroscopy both had a
      sensitivity of approximately 80% with regard to diagnosing endometrial polyps
      (false-positive rates of 24% and 6%, respectively), whereas conventional
      ultrasound missed half of the polyps (sensitivity, 49%; false-positive rate,
      19%). Hysteroscopy was superior to both saline contrast sonohysterography and
      conventional ultrasound with regard to discriminating between benign and
      malignant lesions (sensitivity, 84%, 44%, and 60%; false-positive rate, 15%, 6%
      and 10%, respectively). The risk of malignancy was increased seven-fold (odds
      ratio, 7.3; 95% confidence interval, 1.9-27.8) in women with distension
      difficulties at saline contrast sonohysterography, and two thirds of the women
      with a poorly distensible uterine cavity had a malignant diagnosis. CONCLUSION:
      Saline contrast sonohysterography is as good as hysteroscopy at detecting focally
      growing lesions in the uterine cavity in women with postmenopausal bleeding.
      However, neither hysteroscopy nor saline contrast sonohysterography can reliably
      discriminate between benign and malignant focal lesions. Distension difficulties
      at saline contrast sonohysterography should raise a suspicion of malignancy.

PMID- 11529999
TI  - Determination of the anatomical location of an antenatal intestinal occlusion by
      magnetic resonance imaging.
AB  - Intestinal occlusion occurs in approximately 1 in 3000 births. Its diagnosis can
      be made in utero with ultrasound however, determination of its precise location
      is difficult to achieve. We report herein the feasibility of diagnosing and
      locating a fetal small-intestine occlusion with the use of magnetic resonance
      imaging.

PMID- 11530000
TI  - Combined prenatal ultrasound and magnetic resonance imaging in two fetuses with
      suspected arachnoid cysts.
AB  - Sonography and ultrafast magnetic resonance imaging were used in the prenatal
      assessment of two fetuses with sonographically suspected arachnoid cysts. In one
      case magnetic resonance imaging confirmed the ultrasound diagnosis, in the other
      case magnetic resonance imaging revealed the presence of a midline cyst
      associated with dysgenesis of the corpus callosum. Ultrafast magnetic resonance
      imaging is a useful supplementary imaging method in the evaluation of pregnancies
      complicated by fetal cerebral anomalies.

PMID- 11530001
TI  - Diagnostic and therapeutic problems in a case of prenatally detected fetal
      hydrocolpos.
AB  - We report on a female fetus with prenatally suspected hydrometrocolpos. Postnatal
      evaluation additionally revealed ambiguous genitalia, anorectal atresia,
      vertebral segmentation anomalies and congenital intestinal aganglionosis.
      Colostomy was performed, but postoperative recovery was complicated by pulmonary
      hypertension and renal failure, resulting in death at day 18. Postmortem
      examination furthermore revealed a small ventricular septal defect, as well as
      rectovaginal and urethrovaginal fistulae, causing massive dilatation of the
      septated vagina (hydrocolpos). The possibility of an overlapping VACTERL and
      MURCS association is discussed.

PMID- 11530002
TI  - Prenatal diagnosis of an ectopic intrathoracic kidney in right-sided congenital
      diaphragmatic hernia using color Doppler ultrasonography.
AB  - The prenatal sonographic features of a fetus with right-sided congenital
      diaphragmatic hernia diagnosed at 33 weeks are presented. Color Doppler
      demonstrated an abnormal course of the right renal artery, arising from the aorta
      and feeding the intrathoracic right kidney. This case report stresses the role of
      color Doppler in defining which organs have herniated in fetuses with
      diaphragmatic hernia.

PMID- 11530003
TI  - Does acute hypoxia cause fetal arterial blood flow redistribution?
AB  - Chronic fetal hypoxia in fetal growth restriction due to impaired placentation is
      associated with centralization of blood flow to the vital organs, such as brain,
      heart and adrenal glands, in order to maintain oxygenation. There is a
      correlation between fetal hypoxemia and low impedance to blood flow in the middle
      cerebral artery. However, there is no association between abnormal flow velocity
      waveforms and fetal distress in an unselected population, and this reported case
      also suggests that Doppler ultrasound is of no value in identifying acute fetal
      distress.

PMID- 11530004
TI  - Prenatal diagnosis of an epignathus: a case report and review of the literature.
AB  - An epignathus is an extremely rare form of teratoma that arises from the oral
      cavity, most commonly from the palate. We describe a case identified
      sonographically at 17 weeks' gestation after a raised maternal serum alpha
      fetoprotein was recorded. This pregnancy was terminated but we review the
      literature over the last 10 years and describe the management options available
      in such cases.

PMID- 11530005
TI  - Fetal intestinal volvulus: a clinico-sonographic finding.

PMID- 11530006
TI  - Structural basis of bacterial photosynthetic reaction centers.
AB  - The photosynthetic reaction center (RC) is the first membrane protein whose three
      dimensional structure was revealed at the atomic level by X-ray crystallograph
      more than fifteen years ago. Structural information about RC made a great
      contribution to the understanding of the reaction mechanism of the complicated
      membrane protein complex. High-resolution structures of RCs from three
      photosynthetic bacteria are now available, namely, those from two mesophilic
      purple non-sulfur bacteria, Blastochloris viridis and Rhodobacter sphaeroides,
      and that from a thermophilic purple sulfur bacterium, Thermochromatium tepidum.
      In addition, a variety of structural studies, mainly by X-ray crystallography,
      are still being performed to give more detailed insight into the reaction
      mechanism of this membrane protein. This review deals with structural studies of
      bacterial RC complexes, and a discussion about the electron transfer reaction
      between RCs and electron donors is the main focus out of several topics addressed
      by these structural studies. The structural data from three RCs and their
      electron donors provided reliable models for molecular recognition in the primary
      step of bacterial photosynthesis.

PMID- 11530007
TI  - Removal of inhibitory substances with recombinant fibronectin-CH-296 plates
      enhances the retroviral transduction efficiency of CD34(+)CD38(-) bone marrow
      cells.
AB  - In retroviral gene transduction, the efficiency of viral infection was reduced by
      the proteoglycans and some other materials secreted by the producer lines. In
      order to remove these inhibitors we have developed the rFN-CH-296-facilitated
      protocol. Because the rFN-CH-296 molecule has strong ability to bind a retroviral
      vector, rFN-CH-296 bound plates are utilized to wash out the unbound putative
      inhibitors present in a virus supernatant. The gene transduction efficiencies of
      human CD34(+)CD38(-) BMCs with a GALV-pseudotyped vector and the rFN-CH-296
      facilitated protocol were compared with the protocol without a coating plate with
      CH-296, the mean gene transduction efficiencies being found to be 95.5 and 71.1%,
      respectively.

PMID- 11530008
TI  - Arginine-specific ADP-ribosyltransferase on the surface of gizzard smooth muscle
      cells and the involvement of phosphatidylinositol 3-kinase in maintaining the
      activity of this transferase.
AB  - An arginine-specific ADP-ribosyltransferase activity was detected in chicken
      gizzard smooth muscle, and the specific activity is highest in the membrane
      fraction. This transferase is released from the membrane fraction by
      phosphatidylinositol-specific phospholipase C (PI-PLC), suggesting that it is a
      glycosylphosphatidylinositol (GPI)-anchored protein. When primary cultured
      gizzard smooth muscle cells (SMCs) were incubated with [adenylate-(32)P]NAD,
      several proteins were labeled. The labeling was inhibited by preincubation of the
      cells with PI-PLC, or by the addition of L-arginine to the reaction, and was
      sensitive to hydroxylamine treatment. The activity of the transferase was
      maintained in differentiated SMCs cultured with insulin, but was dramatically
      decreased concomitantly with cell dedifferentiation induced by serum or a
      specific PI3-kinase inhibitor, LY294002. These results indicate that the GPI
      anchored arginine-specific ADP-ribosyltransferase is expressed on the surface of
      differentiated SMCs and can modify several cell surface proteins. Our results
      also suggest that PI3-kinase is involved in the regulation of transferase
      activity during differentiation.

PMID- 11530009
TI  - Galactosyl transfer catalyzed by thermostable beta-glycosidases from Sulfolobus
      solfataricus and Pyrococcus furiosus: kinetic studies of the reactions of
      galactosylated enzyme intermediates with a range of nucleophiles.
AB  - The transfer of a galactosyl group from an enzyme to a number of neutral primary
      alcohols, phenol and azide has been studied during the reactions at 80 degrees C
      of thermostable beta-glycosidases from Sulfolobus solfataricus (Ss beta Gly) and
      Pyrococcus furiosus (CelB) with 2-nitrophenyl beta-D-galactopyranoside or lactose
      (4-O-beta-D-galactopyranosyl D-glucopyranose) as substrates. The rate constant
      ratios, k(Nu)/k(water), for partitioning of the galactosylated enzyme
      intermediates between reaction with nucleophiles (k(Nu), M(-1) s(-1)) and water
      (k(water), s(-1)) have been determined from the difference in the initial
      velocities of the formation of 2-nitrophenol or D-glucose, and D-galactose. The
      results show that hydrophobic bonding interactions contribute approximately 8 kJ
      mol(-1) to the stabilization of the transition state for the reaction of
      galactosylated enzyme intermediates of Ss beta Gly and CelB with 1-butanol,
      compared to the transition state for the enzymatic reaction with methanol. The
      leaving group/nucleophile binding sites of Ss beta Gly and CelB appear about 0.8
      times as hydrophobic as n-octanol. Values of k(Nu)/k(water) for reactions of
      galactosylated Ss beta Gly with ethanol and substituted derivatives of ethanol
      show no clear dependence on the pK(a) of the primary hydroxy group of these
      nucleophiles in the pK(a) range 12.4-16.0. The binding of phenol with the
      galactosylated enzyme intermediates of Ss beta Gly and CelB occurs in a form that
      is mainly nonproductive pertaining to beta-galactoside synthesis. Neither enzyme
      catalyzes galactosyl transfer to azide ion. A model is proposed for the
      interaction of neutral nucleophiles at an extended acceptor site of the
      galactosylated enzymes.

PMID- 11530011
TI  - Xenopus eggs express an identical DNA methyltransferase, Dnmt1, to somatic cells.
AB  - In mouse, an oocyte-specific short isoform of DNA methyltransferase-1 (Dnmt1)
      lacking amino terminal 118 amino acid residues exists and plays a crucial role in
      maintaining the methylation state of imprinted genes during early embryogenesis
      [Howell et al. (2001) Cell 104, 829-838]. To address the question of whether or
      not Xenopus oocyte expresses such a short isoform, we raised monoclonal
      antibodies against the amino-terminal portion of Xenopus Dnmt1. Two of the
      isolated monoclonal antibodies, 3C6 and 4A8, were determined to recognize (1-32)
      and (115-126) of Xenopus Dnmt1, respectively. The amounts of Dnmt1 in Xenopus
      eggs were determined to be similar, 10.0 2.5, 8.0 0.8, and 8.2 0.2 ng per egg
      with monoclonal antibodies 3C6 and 4A8, and polyclonal antibodies, respectively.
      This indicated that Dnmt1 in Xenopus mature eggs had an identical amino-terminal
      sequence to the amino acid sequence deduced from the cDNA. Together with the fact
      that Dnmt1 in A6 cells immuno-reacted with all the monoclonal antibodies isolated
      and with the polyclonal antibodies, we concluded that Dnmt1 expressed in Xenopus
      mature eggs possesses an identical amino-terminal sequence to that in somatic
      cells. Immuno-purified Xenopus Dnmt1 in mature eggs showed similar specific
      activity to that in proliferating A6 cells and that of mouse recombinant Dnmt1.

PMID- 11530010
TI  - Osmotic stress induces HB-EGF gene expression via Ca(2+)/Pyk2/JNK signal cascades
      in rat aortic smooth muscle cells.
AB  - The present study was undertaken in an attempt to clarify the pathway by which
      hyperosmotic stress induces HB-EGF gene expression in rat aortic smooth muscle
      cells (RASMC). Hyperosmotic stress induced by a high concentration of glucose or
      mannitol resulted in an increase in HB-EGF mRNA level in a dose- and time
      dependent manner. HB-EGF induction was blocked by curcumin, a c-jun/fos antisense
      oligonucleotide and a dominant-negative mutant of JNK1. Electrophoretic mobility
      shift assay also showed the involvement of AP-1 in HB-EGF gene expression by
      glucose. In addition, hyperosmotic stress induced rapid phosphorylation of Pyk2
      in RASMC. TPA and calcium chelating agents (BAPTA-AM and EGTA) blocked Pyk2
      phosphorylation and HB-EGF gene expression. Furthermore, HB-EGF gene expression
      and JNK activation by hyperosmotic stress were sensitive to PP2, an Src kinase
      specific inhibitor. These findings indicate that hyperosmotic stress activates
      JNK via calcium-Pyk2 signaling cascades, which in turn induce HB-EGF gene
      expression.

PMID- 11530012
TI  - A method for micrometer resolution patterning of primary culture neurons for SPM
      analysis.
AB  - In this work we present a method for ultra-fine patterning of primary culture
      neuron cell growth, which is compatible for scanning near-field optical atomic
      force microscopy (SNOAM) analysis. SNOAM uses near-field optics to break the
      fundamental diffraction limit imposed on normal microscopy. SNOAM can achieve sub
      100 nm optical resolutions, but requires transparent, open substrates. The
      ability to do physiological measurements on patterns of neurons, combined with
      ultra high resolution optical and fluorescent analysis, is useful in the study of
      long-term potentiation. The patterning method consists of chemical guidance with
      an element of physical confinement and allows for ultra-fine patterning of neural
      growth on transparent glass substrates. Substrates consist of microfabricated
      perfluoropolymer barrier structures on glass. Poly-L-lysine was selectively
      deposited using a silicone-based microfluidic stencil aligned to the
      perfluoropolymer/glass substrate. Primary culture neurons were extracted from 8
      day-old chicks and grown for 3 days to form good networks. This patterning system
      shows very specific growth with patterning separations down to the level of
      individual neurites. Fluorescent imaging was carried out on both cell viability
      during growth and immuno-tagged microtubule-associated proteins on the neurites.
      Neurons inside the patterned structures were imaged and analyzed with a tapping
      mode SNOAM.

PMID- 11530013
TI  - A unique phosphatidylinositol bearing a novel branched-chain fatty acid from
      Rhodococcus equi binds to influenza virus hemagglutinin and inhibits the
      infection of cells.
AB  - From the aquatic bacterium Rhodococcus equi strain S(420), we isolated a
      substance that strongly binds to influenza viruses. Structural analyses revealed
      that it is a unique type of phosphatidylinositol (PtdIns) bearing a branched
      chain fatty acid (14-methyloctadecanoic acid). In a TLC/virus-binding
      immunostaining assay, this PtdIns bound to all subtypes of hemagglutinin (HA) of
      influenza A viruses tested, isolated from humans, ducks and swine, and also to
      human influenza B viruses. Furthermore, the PtdIns significantly prevented the
      infection of MDCK cells by influenza viruses, and also inhibited the virus
      mediated hemagglutination and low pH-induced hemolysis of human erythrocytes,
      which represents the fusogenic activities of the viral HA. We also used purified
      hemagglutinin instead of virions to examine the interaction between viral HA and
      PtdIns, showing that the PtdIns binds to hemagglutinin. These findings indicate
      that the inhibitory mechanism of PtdIns on the influenza virus infection may be
      through its binding to viral HA spikes and host cell endosomal/lysosomal
      membranes, which are mediated by the function of viral HA.

PMID- 11530014
TI  - The promoter of mouse transcription repressor bach1 is regulated by Sp1 and trans
      activated by Bach1.
AB  - The Maf recognition element (MARE) is regulated by both activators and
      repressors. Bach1 and Bach2 repress MARE-dependent transcription by forming
      heterodimers with Maf-related oncoproteins. In order to gain an understanding of
      the regulation of bach1 gene expression, we analyzed the structure of the mouse
      bach1 gene. Comparison of the exon-intron structure of the bach1 gene with those
      of other NF-E2-related genes indicated that bach1 and bach2 constitute an
      evolutionarily distinct subfamily among bZip factors. The bach1 promoter region
      contains two GC boxes that are important for its basal activity and are bound by
      Sp1 in K562 cell extracts. In addition, we found an evolutionarily conserved MARE
      like element located downstream of the transcription initiation site. Deletion of
      this element resulted in a higher promoter activity in K562 cells. Bach1 trans
      activated its own promoter depending on the presence of the MARE-like element in
      co-transfection assays. However, Bach1 did not bind to the MARE-like element in
      electrophoretic mobility shift assays (EMSA). These results suggest that Bach1
      activates its own promoter indirectly by inhibiting the putative repressor. Such
      a positive feedback regulation by the repressor Bach1 may play an important role
      in maintaining the expression of Bach1 while consolidating repression of other
      genes with MARE.

PMID- 11530015
TI  - Membrane fusion between liposomes composed of acidic phospholipids and neutral
      phospholipids induced by melittin: a differential scanning calorimetric study.
AB  - Melittin-induced membrane fusion between neutral and acidic phospholipids was
      examined in liposome systems with a high-sensitivity differential scanning
      calorimeter. Membrane fusion could be detected by calorimetric measurement by
      observing thermograms of mixed liposomal lipids. The roles of hydrophobic and
      electrostatic interactions were investigated in membrane fusion induced by
      melittin. Melittin, a bee venom peptide, is composed of a hydrophobic region
      including hydrophobic amino acids and a positively charged region including basic
      amino acids. When phosphatidylcholine liposomes were prepared in the presence of
      melittin, reductions in the phase transition enthalpies were observed in the
      following order; dimyristoylphosphatidylcholine (DMPC) >
      dipalmitoylphosphatidylcholine (DPPC) > distearoylphosphatidylcholine (DSPC) >
      dielaidoylphosphatidylcholine (DEPC). The plase transition enthalpy of an acidic
      phospholipid, dipalmitoylphosphatidylserine (DPPS), was raised by melittin at low
      concentrations, then reduced at higher concentrations. DPPC liposomes prepared in
      melittin solution were fused with DPPS liposomes when the liposomal dispersions
      were mixed and incubated. Similar fusion was observed between
      dipalmitoylphosphatidylcholine and dimyristoylphosphatidic acid (DMPA) liposomes.
      These results indicate that a peptide including hydrophobic and basic regions can
      mediate membrane fusion between neutral and acidic liposomes by hydrophobic and
      electrostatic interactions.

PMID- 11530016
TI  - The structure and function of the replication initiator protein (Rep) of pSC101:
      an analysis based on a novel positive-selection system for the replication
      deficient mutants.
AB  - Plasmid pSC101 encodes a 37.5 kDa Rep (RepA) protein, which binds to three 21
      base repeats (DR-1, DR-2, and DR-3) in the replication origin region (ori) of the
      plasmid to initiate replication. Rep also binds to two palindromic sequences (IR
      1 and IR-2) which overlap the rep promoter. The binding of Rep to IR-2 represses
      the production of Rep itself. It is highly likely that the balance of these
      functions of Rep plays a major role in controlling the copy number of pSC101. In
      this study, we developed a positive-selection system for replication-deficient
      mutants of the initiator protein. This system can be applied to the study of
      other replication systems by changing ori and rep of pSC101 to the corresponding
      genes. Thirty-four replication-deficient (Ini(-)) mutants were isolated with this
      system, and analyzed as to the relation between the structure and function of the
      Rep protein. Seventeen of these 34 Ini(-) mutants were found to lack auto
      repressor activity as well as initiator activity. DNA sequence analysis showed
      that one-third (from the C-terminus) of Rep is dispensable for the auto-repressor
      activity, while the initiator activity seems to require the whole protein.

PMID- 11530017
TI  - Purification and characterization of a new RGD/KGD-containing dimeric
      disintegrin, piscivostatin, from the venom of Agkistrodon piscivorus piscivorus:
      the unique effect of piscivostatin on platelet aggregation.
AB  - Piscivostatin, a novel dimeric disintegrin containing Arg-Gly-Asp (RGD) and Lys
      Gly-Asp (KGD) sequences, was isolated from the venom of Agkistrodon piscivorus
      piscivorus. The molecule consisted of two chains designated as the alpha and beta
      chains, comprising 65 and 68 amino acid residues, respectively. Piscivostatin had
      two binding motifs recognized by platelet glycoprotein IIb/IIIa (GPIIb/IIIa), and
      the biological activity of dimeric disintegrin piscivostatin toward platelet
      aggregation differed from those of other monomeric disintegrins such as
      trimestatin and echistatin. We measured platelet aggregation by the laser light
      scattering method during the process of ADP-induced platelet aggregation. Both
      dimeric and monomeric disintegrins inhibited the formation of small (9 to 25
      microm in diameter), medium-sized and large aggregates (25 to 70 microm in
      diameter) in a dose-dependent manner. The platelet aggregates disaggregated after
      reaching a maximal number on either treatment with ADP alone or monomeric
      disintegrin/ADP. However, the small aggregates did not disaggregate on treatment
      with piscivostatin/ADP even when applied over time. When washed platelets were
      incubated with an anti-GPIIb/IIIa monoclonal antibody, PT25-2, which induces
      conformational changes of GPIIb/IIIa to a form accessible to fibrinogen and other
      adhesion proteins without platelet activation, piscivostatin induced a platelet
      shape change alone with no aggregate formation. The present study indicated that
      piscivostatin has two unique contradictory activities; acting as a double
      inhibitor of platelet aggregation and platelet aggregate dissociation.

PMID- 11530018
TI  - Changing the amino acid specificity of yeast tyrosyl-tRNA synthetase by genetic
      engineering.
AB  - In an attempt to generate mutant aminoacyl-tRNA synthetases capable of charging
      non-canonical amino acids, a series of yeast tyrosyl-tRNA synthetase (TyrRS)
      mutants was constructed by site-specific mutagenesis of putative active site
      residues, which were deduced by analogy with those of Bacillus stearothermophilus
      TyrRS. Among these mutants, one with the replacement of tyrosine at position 43
      by glycine, "Y43G," was found to be able to utilize several 3-substituted
      tyrosine analogues as substrates for aminoacylation. The catalytic efficiency
      (k(cat)/K(m)) of mutant Y43G for aminoacylation with L-tyrosine was about 400
      fold decreased as compared to that of the wild-type TyrRS. On the other hand, the
      ability to utilize 3-iodo-L-tyrosine was newly generated in this mutant TyrRS,
      since the wild-type TyrRS could not accept 3-iodo-L-tyrosine at all under
      physiological conditions. This mutant TyrRS should serve as a new tool for site
      specific incorporation of non-canonical amino acids, such as those in 3
      substituted tyrosine analogues, into proteins in an appropriate translation
      system in vivo or in vitro.

PMID- 11530019
TI  - Characterization of a membrane-bound arginine-specific serine protease from rat
      intestinal mucosa.
AB  - Previously we isolated and characterized a membrane-bound, arginine-specific
      serine protease from pig intestinal mucosa [J. Biol. Chem. 269, 32985-32991
      (1994)]. For further characterization of this type of enzyme, we cloned a cDNA
      from rat intestinal mucosa encoding the precursor of a similar protease. The
      partial amino acid sequences determined for the pig enzyme were found to be
      shared almost completely by the rat enzyme. The serine protease domain of the rat
      enzyme, heterologously expressed in Escherichia coli, specifically cleaved Arg
      (or Lys)-X bonds with a marked preference for Arg-Arg or Arg-Lys, similar to the
      pig enzyme. The mRNA for the rat enzyme was shown to be distributed mainly in
      intestine, and the enzyme was detected in the duodenal mucosa as a 70 kDa
      protein. Immunohistochemical analysis of the small intestinal tissue showed that
      the enzyme is localized mainly on brushborder membranes.

PMID- 11530020
TI  - Domain and genomic sequence analysis of bdellin-KL, a leech-derived trypsin
      plasmin inhibitor.
AB  - Bdellin-KL is a trypsin-plasmin inhibitor from Hirudo nipponia, whose N-terminal
      sequence was identified as a non-classical Kazal-type. A cDNA clone encoding the
      inhibitor was isolated by reverse transcription-PCR and 5' rapid amplification of
      cDNA ends. The cDNA showed an open reading frame of 155 amino acids comprising
      one signal peptide and two separated domains. The C-terminal domain consists of
      distinct internal repeats, including HHEE and HHDD. The bdellin-KL sequence, from
      the constructed genomic library of Korean leech, was determined for the 2109
      bases comprising the open reading frame and flanking regions (3' and 5'). The
      promoter region contains potential regulatory sequence motifs, including TATA,
      CAAT, and GC boxes. To characterize the properties of each domain, an N-terminal
      fragment was prepared by limited proteolysis of the intact protein. The
      inhibitory activity of the region was as potent as that of the intact protein.
      This suggests that the compact domain plays an important part in the inhibitory
      action of bdellin-KL. The C-terminal domain was revealed to have binding affinity
      to ions such as Ca(2+), Zn(2+), Fe(3+), and Fe(2+) without an influence on the
      inhibitory activity. This study demonstrates that bdellin-KL may be a novel
      bifunctional protein with two distinct domains.

PMID- 11530021
TI  - Effects of five-tryptophan mutations on structure, stability and function of
      Escherichia coli dihydrofolate reductase.
AB  - To elucidate the roles of tryptophan residues in the structure, stability, and
      function of Escherichia coli dihydrofolate reductase (DHFR), its five tryptophan
      residues were replaced by site-directed mutagenesis with leucine, phenylalanine
      or valine (W22F, W22L, W30L, W47L, W74F, W74L, W133F, and W133V). Far-ultraviolet
      circular dichroism (CD) spectra of these mutants reveal that exciton coupling
      between Trp47 and Trp74 strongly affects the peptide CD of wild-type DHFR, and
      that Trp133 also contributes appreciably. No additivity was observed in the
      contributions of individual tryptophan residues to the fluorescence spectrum of
      wild-type DHFR, Trp74 having a dominant effect. These single-tryptophan mutations
      induce large changes in the free energy of urea unfolding, which showed values of
      1.79-7.14 kcal/mol, compared with the value for wild-type DHFR of 6.08 kcal/mol.
      Analysis of CD and fluorescence spectra suggests that thermal unfolding involves
      an intermediate with the native-like secondary structure, the disrupted Trp47
      Trp74 exciton coupling, and the solvent-exposed Trp30 and Trp47 side chains. All
      the mutants except W22L (13%) retain more than 50% of the enzyme activity of wild
      type DHFR. These results demonstrate that the five tryptophan residues of DHFR
      play important roles in its structure and stability but do not crucially affect
      its enzymatic function.

PMID- 11530022
TI  - Binding of annexins to lung lamellar bodies and the PMA-stimulated secretion of
      annexin V from alveolar type II cells.
AB  - To identify lung lamellar body (LB)-binding proteins, the fractions binding to LB
      Sepharose 4B in a Ca(2+)-dependent manner from the lung soluble fractions were
      analyzed with Mono Q column. Four annexins (annexins III, IV, V, and VIII) were
      identified by partial amino acid sequence analyses as the LB-binding proteins in
      the lung soluble fractions. A control experiment using phospholipid
      (phosphatidylserine/phosphatidylglycerol/phosphtidylcholine) liposome-Sepharose
      4B revealed that annexins III, IV and V were the Ca(2+)-dependent proteins
      binding to the column in the lung soluble fractions, while annexin VIII was not
      detected. Thus, annexin VIII might preferentially bind to LB. On the other hand,
      the only Ca(2+)-dependent LB-binding protein identified in the bronchoalveolar
      lavage fluids was annexin V. It was further demonstrated that annexin V was
      secreted by isolated alveolar type II cells from rats and that the secretion was
      stimulated by the addition of phorbol ester (PMA), a potent stimulator of
      surfactant secretion. The PMA-dependent stimulation of annexin V was attenuated
      by preincubation with surfactant protein-A (SP-A), a potent inhibitor of
      surfactant secretion. As LB is thought to be an intracellular store of pulmonary
      surfactant, which is secreted by alveolar type II cells, annexin V is likely to
      be secreted together with the lamellar body.

PMID- 11530023
TI  - Formation of retinoyl-CoA in rat tissues.
AB  - Retinoylation (retinoic acid acylation) is a posttranslational modification of
      proteins occurring in a variety of cell types in vitro and in tissues in vivo.
      The widespread occurrence of retinoylation suggests that it may play a role in
      many effects of retinoic acid (RA) on cells. One metabolic pathway for
      retinoylation involves the intermediate formation of retinoyl-CoA and subsequent
      transfer and covalent binding of the retinoyl moiety to protein. However, such
      reactions are not well known. To gain further insight into retinoylation, we
      studied the synthesis of retinoyl-CoA, the first step in this multi-stage
      process. The formation of [(3)H]-retinoyl-CoA was determined in incubation
      mixtures containing rat liver extract, [(3)H]-RA, ATP, CoA, and MgCl(2). No
      retinoyl-CoA was formed in the presence of boiled extract, or in the absence of
      ATP, CoA, or MgCl(2) (a divalent cation). A greater amount of retinoyl-CoA was
      obtained from microsomal fractions of rat liver than from other subfractions. The
      presence of retinoyl-CoA was also detected in extracts prepared from rat testis,
      kidney, brain, spleen, and pancreas. The level of retinoylation in various tissue
      extracts was related directly to the amount of retinoyl-CoA formed. V(max) and
      K(m) values for RA in the formation of liver retinoyl-CoA were estimated to be
      1.0 x 10(-4) micromol/min/mg protein and 24 nM, respectively. Synthesis of
      retinoyl-CoA was suppressed by fatty acids and fatty acyl-CoAs. These results
      indicate that ATP-dependent generation of retinoyl-CoA occurs in rat tissues and
      may play a significant physiological role in RA actions mediated by
      retinoylation.

PMID- 11530024
TI  - Glycogen debranching enzyme in bovine brain.
AB  - Glycogen debranching enzyme was partially purified from bovine brain using a
      substrate for measuring the amylo-1,6-glucosidase activity. Bovine cerebrum was
      homogenized, followed by cell-fractionation of the resulting homogenate. The
      enzyme activity was found mainly in the cytosolic fraction. The enzyme was
      purified 5,000-fold by ammonium sulfate precipitation, anion-exchange
      chromatography, gel-filtration, anion-exchange HPLC, and gel-permeation HPLC. The
      enzyme preparation had no alpha-glucosidase or alpha-amylase activities and
      degraded phosphorylase limit dextrin of glycogen with phosphorylase. The
      molecular weight of the enzyme was 190,000 and the optimal pH was 6.0. The brain
      enzyme differed from glycogen debranching enzyme of liver or muscle in its mode
      of action on dextrins with an alpha-1,6-glucosyl branch, indicating an amino acid
      sequence different from those of the latter two enzymes. It is likely that the
      enzyme is involved in the breakdown of brain glycogen in concert with
      phosphorylase as in the cases of liver and muscle, but that this proceeds in a
      somewhat different manner. The enzyme activity decreased in the presence of ATP,
      suggesting that the degradation of brain glycogen is controlled by the
      modification of the debranching enzyme activity as well as the phosphorylase.

PMID- 11530027
TI  - Prospective evaluation of patients with syncope: a population-based study.
AB  - PURPOSE: To determine the diagnostic yield of a standardized sequential
      evaluation of patients with syncope in a primary care teaching hospital. PATIENTS
      AND METHODS: All consecutive patients who presented to the emergency department
      with syncope as a chief complaint were enrolled. Their evaluation included
      initial and routine clinical examination, including carotid sinus massage, as
      well as electrocardiography and basic laboratory testing. Targeted tests, such as
      echocardiography, were used when a specific entity was suspected clinically.
      Other cardiovascular tests (24-hour Holter monitoring, ambulatory loop recorder
      ECG, upright tilt test, and signal-averaged electrocardiography) were performed
      in patients with unexplained syncope after the initial steps. Electrophysiologic
      studies were performed in selected patients only as clinically appropriate.
      Follow-up information on recurrence and mortality were obtained every 6 months
      for as long as 18 months for 94% (n = 611) of the patients. RESULTS: After the
      initial clinical evaluation, a suspected cause of syncope was found in 69% (n =
      446) of the 650 patients, including neurocardiogenic syncope (n = 234, 36%),
      orthostatic hypotension (n = 156, 24%), arrhythmia (n = 24, 4%), and other
      diseases (n = 32, 5%). Of the 67 patients who underwent targeted tests, suspected
      diagnoses were confirmed in 49 (73%) patients: aortic stenosis (n = 8, 1%),
      pulmonary embolism (n = 8, 1%), seizures/stroke (n = 30, 5%), and other diseases
      (n = 3). Extensive cardiovascular workups, which were performed in 122 of the 155
      patients in whom syncope remained unexplained after clinical assessment, provided
      a suspected cause of syncope in only 30 (25%) patients, including arrhythmias in
      18 (60%), all of whom had abnormal baseline ECGs. The 18-month mortality was 9%
      (n = 55, including 8 patients with sudden death); syncope recurred in 15% (n =
      95) of the patients. CONCLUSION: The diagnostic yield of a standardized clinical
      evaluation of syncope was 76%, greater than reported previously in unselected
      patients. Electrocardiogram-based risk stratification was useful in guiding the
      use of specialized cardiovascular tests.

PMID- 11530028
TI  - Achieving and maintaining National Cholesterol Education Program low-density
      lipoprotein cholesterol goals with five statins.
AB  - PURPOSE: Most patients fail to achieve and maintain low-density lipoprotein (LDL)
      cholesterol goals established by the National Cholesterol Education Program
      (NCEP). The Atorvastatin Comparative Cholesterol Efficacy and Safety Study
      (ACCESS) was a randomized study comparing the efficacy and safety of five statins
      and their ability reduce LDL cholesterol to the NCEP target level. SUBJECTS AND
      METHODS: Of 7542 patients screened, 3916 hypercholesterolemic patients were
      randomly assigned to treatment with a statin, beginning with the lowest
      recommended dose (atorvastatin, pravastatin, and simvastatin, 10 mg; fluvastatin
      and lovastatin, 20 mg). If the NCEP target was not achieved, the dose was
      titrated up to the recommended maximum (atorvastatin, fluvastatin, and
      lovastatin, 80 mg; pravastatin and simvastatin, 40 mg). The total duration of
      treatment was 54 weeks. RESULTS: Atorvastatin achieved the greatest mean
      reduction in LDL cholesterol: 36% +/- 11% at 6 weeks (initial dose) and 42% +/-
      13% at 54 weeks. More patients receiving atorvastatin at its initial dose (53%,
      997 of 1888) achieved their NCEP target levels than patients receiving
      simvastatin (38%, 174 of 462), lovastatin (28%, 134 of 472), pravastatin (15%, 71
      of 461), or fluvastatin (15%, 69 of 474) at the initial dose. Atorvastatin
      treated patients were more likely to maintain their target levels from week 6 to
      week 54. The percent reduction in LDL cholesterol achieved at the initial dose
      correlated strongly with the proportion of patients who maintained their goals at
      54 weeks (r = -0.84). CONCLUSION: For patients treated with statins, providing a
      greater margin between the NCEP target level and the achieved LDL cholesterol
      level enhances the likelihood of maintaining NCEP goal levels.

PMID- 11530029
TI  - Positive Epstein-Barr virus heterophile antibody tests in patients with primary
      human immunodeficiency virus infection.
AB  - PURPOSE: To describe three cases of primary human immunodeficiency virus (HIV)
      infection in patients who had laboratory studies consistent with infectious
      mononucleosis. SUBJECTS: We describe 3 patients who presented with a viral
      syndrome, had a positive heterophile antibody test, and were diagnosed with
      primary HIV infection. RESULTS: The results of Epstein-Barr virus serology
      studies in each of these patients were consistent with chronic, but not acute,
      Epstein-Barr virus infection. HIV antibody tests were negative, and HIV RNA was
      >500,000 copies/mL in each patient. CONCLUSIONS: Clinicians should recognize that
      a positive heterophile antibody test in the setting of an acute viral illness
      does not exclude the diagnosis of primary HIV infection, although reactivation of
      latent Epstein-Barr virus infection cannot be ruled out. Patients presenting with
      nonspecific viral syndromes should be assessed for HIV risk behaviors and tested
      for primary HIV infection when appropriate.

PMID- 11530030
TI  - A comparison of short-term treatment with inhaled fluticasone propionate and
      zafirlukast for patients with persistent asthma.
AB  - PURPOSE: To compare the short-term efficacy and safety of low-dose fluticasone
      propionate with that of oral zafirlukast therapy for patients previously treated
      with beta-2-agonists alone, and to evaluate the potential therapeutic benefit of
      switching from zafirlukast to a low-dose inhaled corticosteroid. SUBJECTS AND
      METHODS: This study consisted of a 4-week randomized, double-blind treatment
      period followed by a 4-week open-label period. Two hundred ninety-four patients >
      or =12 years old with asthma previously uncontrolled with beta-2-agonists alone
      were randomly assigned to treatment with low-dose inhaled fluticasone (88 microg
      twice daily) or oral zafirlukast (20 mg twice daily). After 4 weeks, all patients
      discontinued their double-blind therapy and received open-label fluticasone (88
      microg twice daily). Outcomes included pulmonary function, asthma symptoms,
      albuterol use, asthma exacerbations, and adverse events. RESULTS: During the
      double-blind treatment period, fluticasone patients had significantly greater
      improvements in morning peak flow (29.3 L/min vs. 18.3 L/min), percentage of
      symptom-free days (19.8% vs. 11.6%), and daily albuterol use (-1.8 puffs per day
      vs. -1.1 puffs per day) compared with zafirlukast patients (P < or =0.025, each
      comparison). During the open-label treatment period, patients switched from
      zafirlukast to fluticasone experienced additional improvements in morning peak
      flow (17.2 L/min), evening peak flow (13.6 L/min), and FEV(1) (0.11 liter) and
      daily albuterol use (-0.9 puffs daily) compared with values obtained at the end
      of the double-blind treatment period (P < or =0.001, each comparison).
      CONCLUSION: Low-dose fluticasone was more effective than zafirlukast in improving
      pulmonary function and symptoms in patients with persistent asthma. In addition,
      switching patients from zafirlukast to fluticasone further improved clinical
      outcomes.

PMID- 11530031
TI  - A statewide initiative to improve the care of hospitalized pneumonia patients:
      The Connecticut Pneumonia Pathway Project.
AB  - PURPOSE: A statewide quality improvement initiative was conducted in Connecticut
      to improve process-of-care performance and to decrease length of stay for
      patients hospitalized with community-acquired pneumonia. SETTING AND METHODS:
      Data were collected on 1,242 elderly (> or =65 years) pneumonia patients
      hospitalized at 31 of 32 acute care hospitals between January 16, 1995, and March
      15, 1996, and on 1,146 patients hospitalized between January 1, 1997, and June
      30, 1997. Interventions included feedback of performance data (Qualidigm, the
      Connecticut Peer Review Organization), dissemination of an evidence-based
      pneumonia critical pathway (Connecticut Thoracic Society), and sharing of pathway
      implementation experiences (hospitals). Process and outcome measures included
      early antibiotic administration, blood culture collection, oxygenation
      assessment, length of stay, 30-day mortality, and 30-day readmission rates.
      Analyses were adjusted for severity of illness and hospital-specific practice
      patterns. RESULTS: After the statewide initiative, improvements were noted in
      antibiotic administration within 8 hours of hospital arrival (improvement from
      83.4% to 88.8%, relative risk [RR] = 1.21; 95% confidence interval [CI]: 1.10 to
      1.32), oxygenation assessment within 24 hours of hospital arrival (93.6% to
      95.4%; RR = 1.23, 95% CI: 1.11 to 1.38), and length of stay (7 days to 5 days, P
      <0.001). There were no significant changes in blood culture collection within 24
      hours of hospital arrival, blood culture collection before antibiotic
      administration, 30-day mortality, or 30-day readmission rates. CONCLUSIONS:
      Statewide improvements were demonstrated in the care of hospitalized pneumonia
      patients concurrent with a multifaceted quality improvement intervention. Further
      research is needed to separate the effects of the quality improvement
      interventions from secular trends.

PMID- 11530032
TI  - Risk factors for visual loss in giant cell (temporal) arteritis: a prospective
      study of 174 patients.
AB  - OBJECTIVE: To determine the risk factors--especially the effects of
      thrombocytosis--for permanent visual loss in patients with temporal arteritis.
      METHODS: One hundred seventy-four patients with temporal arteritis (147 biopsy
      proven) were prospectively observed for the development of permanent visual loss.
      We used multivariate logistic regression analysis to determine which of 17
      pretreatment characteristics were associated with visual loss. RESULTS: Visual
      ischemic manifestations occurred in 48 (28%) patients, including permanent visual
      loss in 23 (13%) patients. The independent predictors associated with an
      increased risk of permanent visual loss were a history of transient visual
      ischemic symptoms (odds ratio [OR] = 6.3; 95% confidence interval [CI]: 1.4 to
      29; P = 0.02) and a higher platelet count (OR = 3.7 per SD; 95% CI: 1.8 to 7.9; P
      = 0.001). The presence of constitutional symptoms (OR = 0.14; 95% CI: 0.02 to
      0.77, P = 0.01), polymyalgia rheumatica (OR = 0.04; 95% CI: 0.01 to 0.48, P =
      0.02), and C-reactive protein level (OR = 0.35 per SD; 95% CI: 0.13 to 0.92, P =
      0.03) were associated with a reduced risk. Upper limb artery involvement was
      excluded from the multivariate model, as no patients with that problem developed
      permanent visual loss. Of the 87 patients who presented with thrombocytosis
      (platelet count >400 x 10(9)/L), 32 (37%) developed ischemic visual symptoms,
      compared with 16 (18%) of those without thrombocytosis. CONCLUSIONS: An elevated
      platelet count is a risk factor for permanent visual loss in temporal arteritis.
      The finding of thrombocytosis in a patient with suspected temporal arteritis
      should emphasize the need for urgent treatment, with consideration of using
      inhibitors of platelet aggregation or anticoagulation therapy.

PMID- 11530033
TI  - Documentation of discussions about prognosis with terminally ill patients.
AB  - PURPOSE: Previous studies have suggested the importance of communicating with
      patients about prognosis at the end of life, yet the prevalence, content, and
      consequences of such communication have not been fully investigated. The purposes
      of this study were to estimate the proportion of terminally ill inpatients with
      documented discussions about prognosis, describe the nature and correlates of
      such discussions, and assess the association between documented discussions about
      prognosis and subsequent advance care planning. SUBJECTS AND METHODS: Inpatients
      (n = 232) at least 65 years old who had brain, pancreas, liver, gall bladder, or
      inoperable lung cancer were randomly selected from six randomly chosen community
      hospitals in Connecticut. The presence and content of discussions about
      prognosis, advanced care planning efforts, and sociodemographic and clinical
      factors were ascertained by comprehensive review of medical records using a
      standardized abstraction form. RESULTS: Discussions about prognosis were
      documented in the medical records of 89 (38%) patients. Physicians and patients
      were both present during the discussion in 46 (52%) of these cases. Time until
      expected death was infrequently documented. Having a documented discussion about
      prognosis was associated with documented discussions of life-sustaining
      treatments (adjusted odds ratio [OR] = 5.8; 95% confidence interval [CI]: 2.8 to
      12.0) and having a do-not-resuscitate order (adjusted OR = 2.2; 95% CI: 1.1 to
      4.2). CONCLUSIONS: Among terminally ill patients with cancer, discussions about
      prognosis as documented in medical charts are infrequent and limited in scope. In
      some cases, such documented discussions may be important catalysts for subsequent
      discussions of patient and family preferences regarding treatment and future
      care.

PMID- 11530034
TI  - What is cardiac resynchronization therapy?
AB  - Cardiac resynchronization refers to pacing techniques that change the degree of
      atrial and ventricular electromechanical asynchrony in patients with major atrial
      and ventricular conduction disorders. Atrial and ventricular resynchronization is
      usually accomplished by pacing from more than one site in an electrical chamber-
      atrium or ventricle--and occasionally by stimulation at a single unconventional
      site. Resynchronization produces beneficial hemodynamic and antiarrhythmic
      effects by providing a more physiologic pattern of depolarization. Atrial
      resynchronization may prevent atrial fibrillation in selected patients with
      underlying bradycardia or interatrial block. Its antiarrhythmic effect in the
      absence of bradycardia is unclear. Ventricular resynchronization is of far
      greater clinical value than atrial resynchronization. Biventricular (or single
      chamber left ventricular) pacing is beneficial for patients with congestive heart
      failure, severe left ventricular systolic dysfunction, dilated cardiomyopathy
      (either ischemic or idiopathic), and a major left-sided intraventricular
      conduction disorder, such as left bundle branch block. The change in electrical
      activation from resynchronization, which has no positive inotropic effect as
      such, is translated into mechanical improvement with a more coordinated left
      ventricular contraction. Several recent randomized trials and a number of
      observational studies have demonstrated the long-term effectiveness of
      ventricular resynchronization in the above group of patients. The high incidence
      of sudden death among these patients has encouraged ongoing clinical trials to
      evaluate the benefit of a system that combines biventricular pacing and
      cardioversion-defibrillation into a single implantable device.

PMID- 11530035
TI  - Rupture of the pectoralis major muscle in nursing home residents.

PMID- 11530036
TI  - Diagnostic dilemma. Musculoskeletal coccidioidomycosis involving the left wrist.

PMID- 11530037
TI  - Clinical challenges and diagnostic approaches to recognizing acute human
      immunodeficiency virus infection.

PMID- 11530039
TI  - Hospitalists' perceptions of their residency training needs: results of a
      national survey.

PMID- 11530040
TI  - Ocular side effects possibly associated with isotretinoin usage.
AB  - PURPOSE: To evaluate reported ocular side effects associated with isotretinoin
      usage. METHODS: One thousand seven hundred forty-one case reports received from
      spontaneous reporting systems, data from the Drug Safety Section of Roche
      Pharmaceuticals, and the world's literature were evaluated using the World Health
      Organization Causality Assessment Guide of Suspected Adverse Reactions. RESULTS:
      Thirty-eight different signs or symptoms of ocular abnormalities associated with
      isotretinoin usage have been classified as "certain," "probable/likely,"
      "possible," "unlikely," or "conditional/unclassifiable." CONCLUSION: Adverse
      ocular side effects secondary to isotretinoin that are "certain" include abnormal
      meibomian gland secretion, blepharoconjunctivitis, corneal opacities, decreased
      dark adaptation, decreased tolerance to contact lens, decreased vision, increased
      tear osmolarity, keratitis, meibomian gland atrophy, myopia, ocular discomfort,
      ocular sicca, photophobia, and teratogenic ocular abnormalities. Those that are
      "probable/likely" are decreased color vision (reversible) and permanent loss of
      dark adaptation. Those that have a "possible" association include permanent
      keratoconjunctivitis sicca. Suggested guidelines for ocular examination for
      patients on isotretinoin are given.

PMID- 11530041
TI  - Cataract surgery by phacoemulsification in adults with retinopathy of
      prematurity.
AB  - PURPOSE: To report the preoperative, operative, and postoperative factors
      associated with phacoemulsification cataract surgery in adults with retinopathy
      of prematurity. METHODS: Records of patients with retinopathy of prematurity who
      underwent phacoemulsification at The Wilmer Institute between January 1990 and
      January 2000 were retrospectively searched. Seventeen adults (9 women, 8 men)
      with retinopathy of prematurity were identified who had undergone
      phacoemulsification for visually significant cataract or phacomorphic glaucoma
      and who had at least 6 months of postoperative follow-up. RESULTS: Cataract
      extraction by phacoemulsification was performed on 20 eyes. Follow-up ranged from
      6 to 103 months (mean, 32 months). A posterior chamber intraocular lens was
      placed in 18 eyes; two eyes were left aphakic for refractive reasons. Zonular
      weakness was noted in two eyes in which the intraocular lens was suture fixated
      to the sclera. Concomitant trabeculectomy was performed in one eye. Visual acuity
      improved in 18 of 20 eyes and remained unchanged in two eyes. Postoperatively,
      visual acuity was worse than 5/200 in two eyes, 5/200 to worse than 20/100 in
      five eyes, 20/100 to 20/50 in five eyes, and 20/40 or better in eight eyes. One
      eye developed a rhegmatogenous retinal detachment 1 month after cataract surgery;
      the retina was successfully reattached. CONCLUSIONS: Although cataract extraction
      in eyes with regressed retinopathy of prematurity may present challenges, such as
      high myopia, monocularity, glaucoma, and previous ocular surgery,
      phacoemulsification in this series proved to be relatively safe as well as
      visually rehabilitating. The surgeon should be aware of the special
      considerations in this population, alert to potential zonular weakness
      intraoperatively, and careful of increased postoperative risks, including retinal
      detachment.

PMID- 11530042
TI  - The Advanced Glaucoma Intervention Study (AGIS): 9. Comparison of glaucoma
      outcomes in black and white patients within treatment groups.
AB  - PURPOSE: To compare in eyes of black and white patients the progression of
      glaucoma after failure of medical therapy and upon start of surgical
      intervention. DESIGN: Cohort study analysis of data from a randomized clinical
      trial. METHODS: This multicenter study included open-angle glaucoma patients who
      had failed medical therapy: 451 eyes of 332 black patients, 325 eyes of 249 white
      patients. Eyes were randomly assigned to an argon laser trabeculoplasty (ALT)
      trabeculectomy-trabeculectomy (ATT) sequence or a trabeculectomy-ALT
      trabeculectomy (TAT) sequence; they had been followed for 7 to 11 years at
      database closure. Main outcome measures were decrease of visual field (DVF),
      sustained decrease of visual field (SDVF), decrease of visual acuity (DVA),
      sustained decrease of visual acuity (SDVA), and failure of first surgical
      glaucoma intervention. Statistical methods included logistic regression to obtain
      average adjusted black-white odds ratios for binary outcomes, and Cox regression
      to estimate adjusted black-white risk ratios for time-to-event outcomes. RESULTS:
      In the ATT sequence blacks were at lower risk than whites of failure of first
      intervention (ALT, RR = 0.68, P = 0.040). In the TAT sequence blacks were at
      higher risk than whites of failure of the first intervention (trabeculectomy, RR
      = 1.79, P = 0.033), of intraocular pressure > or =18 mm Hg (average OR = 1.41, P
      = 0.026), and of DVF (average OR = 1.78, P = 0.007). In both treatment sequences,
      the average number of prescribed medications was greater for blacks than whites
      (P < or = 0.002). CONCLUSIONS: The results support the hypothesis that after
      failure of medical therapy and upon initiation of surgical intervention, an
      initial intervention with trabeculectomy retards the progression of glaucoma more
      effectively in white than in black patients. The data provide a weak suggestion
      that an initial surgical intervention with ALT retards the progression of
      glaucoma more effectively in black than in white patients.

PMID- 11530043
TI  - Acute effects of insulin on aqueous humor flow in patients with type 1 diabetes.
AB  - PURPOSE: Previous studies reported reduced aqueous humor flow through the
      anterior segment of the eye in patients with type 1 diabetes. This study
      investigates whether reduced flow is the result of the diabetic state or of
      alterations in glucose or insulin concentrations. METHODS: A cross-sectional
      study, involving patients with type 1 diabetes and healthy controls, measured
      aqueous flow at different insulin concentrations. Eleven patients with type 1
      diabetes (hemoglobin A1C = 7.0 +/- 0.3% [mean +/- SEM], normal < 6.5) with no
      microvascular complications and 17 controls were prospectively studied. Controls
      were studied fasting and during a hyperinsulinemic-euglycemic clamp (insulin 2
      mU/kg per minute). Patients with type 1 diabetes were similarly studied during
      two euglycemic clamp procedures (insulin 0.5 and 2.0 mU/kg per minute). Aqueous
      flow was measured by fluorophotometry. Pulsatile ocular blood flow and
      intraocular pressure were measured with a Langham flow probe. RESULTS: Control
      subjects had no change in aqueous flow during fasting and hyperinsulinemic
      conditions (3.0 +/- 0.1 vs 2.8 +/- 0.1 microl per minute). In the patients with
      type 1 diabetes, aqueous flow was not decreased with hyperinsulinemia, compared
      with the low insulin state (P =.7). Compared with control subjects, patients with
      type 1 diabetes had lower aqueous flow during hyperinsulinemia (2.4 +/- 0.1
      microl per minute, P =.03) and at lower insulin conditions (2.6 +/- 0.1 microl
      per minute, P <.05). No differences in intraocular pressure or pulsatile ocular
      blood flow were noted between groups or between insulin states within groups.
      CONCLUSIONS: Aqueous flow is decreased in patients with type 1 diabetes under
      euglycemic conditions of high and relatively low insulin concentrations, despite
      the absence of microvascular complications.

PMID- 11530044
TI  - Plaque radiation therapy for malignant melanoma of the iris and ciliary body.
AB  - PURPOSE: To report on plaque radiation therapy for malignant melanomas involving
      the iris and ciliary body. METHODS: Twenty-two eyes (22 patients) with anterior
      uveal melanomas were treated with (103)Pd ophthalmic plaque radiation therapy.
      Transillumination and ultrasonography were used to evaluate ciliary body
      involvement and posterior iris extension. Plaques were placed onto the cornea to
      treat the anterior tumor margins. The targeted-zone included the tumor and a 2 to
      3 mm tumor-free margin. After plaque removal, patients were examined at 1 day, 7
      days, 4 weeks, and then every 3 to 6 months thereafter. Systemic evaluations for
      possible metastatic disease were performed every 6 months. RESULTS: After plaque
      radiation therapy, the melanomas decreased in thickness (mean 47%) in all 22
      eyes, and no secondary enucleation was performed. One patient died of metastatic
      melanoma 5 years after radiation therapy. Despite anterior plaque placement that
      covered portions of the cornea, no epiphora, eyelash loss, or visually
      significant corneal opacities were noted. Whereas 15 of 21 phakic eyes (71%)
      developed secondary cataract, no eyes developed ischemic or neovascular radiation
      maculopathy. Four eyes were noted to have glaucoma before treatment, and two
      developed it after irradiation. Twenty of 22 eyes (91%) were within 2 lines of
      their pretreatment visual acuity. After radiation, the mean +/- SD follow-up was
      56 +/- 34.4 months (range, 9 to 117 months). CONCLUSIONS: Plaque radiotherapy of
      melanomas involving the iris and ciliary body resulted in excellent local control
      with preservation of vision. Although there was high incidence of secondary
      cataracts, (103)Pd plaque radiation therapy resulted in no visually significant
      corneal opacity or radiation retinopathy.

PMID- 11530045
TI  - Ring melanoma of the anterior chamber angle: a report of fourteen cases.
AB  - PURPOSE: Ring melanoma of the anterior chamber angle is a rare variant of uveal
      melanoma that manifests as circumferential, flat tumor growth predominantly
      confined to the trabecular meshwork and other anterior chamber angle structures.
      We report the clinical and histopathological features, management, and prognosis
      of ring melanoma of anterior chamber angle. METHODS: A retrospective review of
      clinical features, management, histopathologic features, and prognosis was
      performed. Of 8800 patients with uveal melanoma examined on the Oncology Service
      at Wills Eye Hospital over a 25-year period, only 14 patients (0.2%; 14 eyes)
      were classified clinically as ring melanoma of the anterior chamber angle. In no
      case was there appreciable involvement of the iris or ciliary body on clinical
      examination. RESULTS: The patients were followed elsewhere for a mean of 8 months
      before intraocular malignancy was suspected. Upon referral to the Oncology
      Service, the intraocular pressure was greater than 22 mm Hg in the affected eye
      in all patients (mean, 36 mm Hg; median, 35 mm Hg; range, 24 to 48 mm Hg), and
      all patients were using at least two glaucoma medications. The melanoma
      infiltrated the anterior chamber angle for a mean of 10 clock hours (range, 8 to
      12 clock hours). Tumor management consisted of enucleation in 13 cases and plaque
      radiotherapy in one case. Histopathologic examination revealed epithelioid cell
      type melanoma in one case, mixed cell type in nine, and spindle cell type in
      four. Of the 13 patients who underwent enucleation, tumor cells were found within
      the Schlemm canal in all cases. Five cases displayed invasion of the intrascleral
      canals, and three showed episcleral invasion. With the exception of two recent
      cases, 12 patients were followed for a mean of 64 months (median, 47 months;
      range, 23 to 225 months). Distant metastasis to the liver was detected in three
      of 12 patients (25%) after a mean follow-up of 78 months (median, 70; range, 37
      to 128 months). CONCLUSIONS: Ring melanoma of the trabecular meshwork and angle
      structures is a rare variant of diffuse uveal melanoma. It often masquerades as
      unilateral glaucoma and can be difficult to recognize clinically unless careful
      comparative gonioscopy is performed. Despite the relatively small tumor volume,
      life prognosis is guarded with distant metastasis in 25% at mean 6 years follow
      up.

PMID- 11530046
TI  - Randomized clinical trial of cryotherapy versus laser photocoagulation for
      retinopexy in conventional retinal detachment surgery.
AB  - PURPOSE: To investigate whether the method of retinopexy influences the visual
      recovery rate and the breakdown of the blood-ocular barrier after conventional
      retinal detachment surgery. METHODS: Forty-eight patients (48 eyes) with primary
      rhegmatogenous retinal detachment entered into the study. All eyes were phakic,
      had an attached macula, and were scheduled for conventional scleral buckling
      surgery. Patients were randomly assigned to have either laser or cryotherapy for
      retinopexy. All visual acuity and flare measurements were performed by a masked
      observer. The interventional procedure was cryopexy at the time of scleral
      buckling surgery or postoperative (4 weeks) laser photocoagulation. Visual acuity
      testing with ETDRS chart and aqueous flare measurement with laser flare
      photometry were performed by a masked observer at standard intervals:
      preoperatively and 1 day, 7 days, 4 weeks, and 10 weeks postoperatively. Analysis
      of covariance by multiple linear regression was used for statistical evaluation.
      RESULTS: Postoperative flare values from patients receiving cryotherapy were
      significantly higher at each measurement point in time (P < or =.001). The visual
      recovery was slower in the patients receiving cryotherapy (1 week, P =.003; 4
      weeks, P =.03; 10 weeks, P =.081). CONCLUSION: Laser flare photometry proved
      sufficiently sensitive to quantify an increase in aqueous flare after limited
      external retinal cryotherapy. Postoperative flare, as a measure of blood-ocular
      barrier breakdown, was significantly higher and visual recovery slower in the
      cryotherapy group. Visual acuity after 10 weeks was not significantly different
      between both groups.

PMID- 11530047
TI  - Correlation between optical coherence tomography data and biomicroscopic
      interpretation of idiopathic macular hole.
AB  - PURPOSE: This study was designed to assess the new clinical information given by
      optical coherence tomography in patients with idiopathic macular hole. METHODS:
      Sixty-one consecutive eyes of 47 patients with idiopathic macular hole at
      different stages of development were studied clinically. Patients with myopia,
      epiretinal macular membrane, and any other ocular disease were excluded. Best
      refracted visual acuity and biomicroscopic fundus examination with macular
      contact lens were performed. Optical coherence tomography was performed through a
      dilated pupil. The optical coherence tomography findings were correlated with the
      Gass biomicroscopic classification of idiopathic macular hole. RESULTS: Optical
      coherence tomography provided different or additional information in 22 of 24
      eyes (91.7%) biomicroscopically classified in stages 1-A and stage 1-B, according
      to the Gass macular hole classification, and in seven of 37 eyes (18.9%)
      biomicroscopically classified in stages 2, 3, and 4. The main difference from
      Gass biomicroscopic classification was a macular pseudocyst instead of a foveolar
      detachment in the first stages. The main additional optical coherence tomography
      observation, not detected biomicroscopically, was the presence of retinal tissue
      on the bottom of the macular hole. Optical coherence tomography may be
      particularly useful in evaluation of early stages in development of idiopathic
      macular hole. CONCLUSIONS: Compared with classic biomicroscopical observation,
      optical coherence tomography frequently gives different or additional information
      on idiopathic macular hole, especially in its early stages. Correct diagnosis and
      surgical indication of idiopathic macular hole may benefit from optical coherence
      tomography imaging.

PMID- 11530048
TI  - Assessment of nuclear sclerosis after nonvitrectomizing vitreous surgery.
AB  - PURPOSE: Nuclear sclerosis develops frequently after successful pars plana
      vitrectomy. We evaluated changes in the degree of nuclear sclerosis after
      nonvitrectomizing vitreous surgery for idiopathic epimacular proliferation.
      METHODS: Forty-one consecutive patients (41 eyes) underwent removal of idiopathic
      epimacular proliferation by nonvitrectomizing vitreous surgery and were followed
      postoperatively for at least 12 months. Visual acuity, refractive error, slit
      lamp biomicroscopy, and Scheimpflug photographs were assessed preoperatively and
      postoperatively to evaluate changes in the degree of lenticular opacification.
      Quantitative analysis of the nuclear sclerosis was performed by densitometry with
      Scheimpflug photographs performed on only the last 21 patients. We evaluated
      these measurements by comparing statistically the preoperative and postoperative
      difference between both eyes (operative eye minus nonoperative ocular data).
      RESULTS: There was no significant difference in the progression of nuclear
      sclerosis or degree of myopic shift between the operated and fellow eyes during
      postoperative follow-up (mean +/- SD, 22 +/- 8 months; median, 22 months; range,
      12 to 48 months). The average preoperative and postoperative refractive errors in
      operated eyes were 0.0 +/- 2.4 diopters and 0.1 +/- 2.5 diopters, respectively;
      the average difference in the refractive errors between both eyes was -0.2 +/-
      0.7 diopter preoperatively and -0.2 +/- 0.9 diopter postoperatively (P =.961,
      paired t test). The average preoperative and postoperative nuclear density values
      by Scheimpflug photography in 21 operated eyes were, respectively, 72 +/- 18
      nuclear density units and 75 +/- 17 nuclear density units; the average difference
      in nuclear density values between both eyes was -1 +/- 4 nuclear density units
      preoperatively and 0 +/- 6 nuclear density units postoperatively (P =.631, paired
      t test). CONCLUSION: Progression of nuclear sclerotic cataract based on changes
      in refractive error and Scheimpflug photography was not observed after
      nonvitrectomizing vitreous surgery.

PMID- 11530049
TI  - Macular changes after peeling of the internal limiting membrane in macular hole
      surgery.
AB  - PURPOSE: To report the incidence of macular changes following pars plana
      vitrectomy with peeling of the internal limiting membrane (ILM) for idiopathic
      macular hole. DESIGN: Prospective consecutive series. METHODS: In a prospective
      study 105 eyes of 105 patients underwent vitrectomy for idiopathic macular holes.
      Surgery consisted of a standard three-port vitrectomy, induction of a posterior
      hyaloid detachment, removal of epiretinal membranes including the ILM, fluid-air
      exchange and intraocular gas tamponade (15% hexafluoroethane (C2F6) gas mixture)
      followed by head-down positioning for at least five days. No adjuvants were used
      during surgery. In addition to the clinical examination, static microperimetry
      using a Rodenstock scanning laser ophthalmoscope (SLO-105) was performed pre- and
      6 or 12 weeks postoperatively. The stimulus size was 0.2 degrees (Goldmann II),
      intensities employed were 0 and 12 dB. For all tests, 20-degree fields were used.
      RESULTS: Anatomic closure of macular holes was achieved in 92 (87.6%) of 105
      patients by one operation. Eight patients underwent a successful second
      procedure. The closure rate after two operations was 95.2%. Best corrected visual
      acuity increased from a median of 0.2 (range 0.05 to 0.5) preoperatively to a
      median of 0.5 (range 0.05 to 1.0) postoperatively. Anatomical macular changes
      were found in 8 (7.6%) patients: There were two cases of macular edema following
      secondary cataract extraction and six cases of retinal pigment epithelium
      changes. Formation of postoperative epiretinal membranes or late reopenings were
      not noted. Small, mostly asymptomatic paracentral scotomata were seen in 59
      (56.2%) of 105 patients. CONCLUSION: Anatomical changes of the macula following
      vitrectomy with removal of the ILM are infrequent. However, paracentral scotomata
      observed in our series might be caused by a trauma to the nerve fibers during ILM
      peeling. To achieve reliable results a standardized procedure for microperimetry
      should be developed.

PMID- 11530050
TI  - Vitrectomy for diabetic macular edema: the role of posterior vitreous detachment
      and epimacular membrane.
AB  - PURPOSE: To evaluate the surgical efficacy of pars plana vitrectomy on eyes with
      diabetic macular edema in the presence or absence of a complete posterior
      vitreous detachment and with or without an epimacular membrane. METHODS: Pars
      plana vitrectomy was performed on 30 eyes of 29 cases with diabetic macular
      edema. Visual acuity was measured, and retinal thickness was determined by
      optical coherence tomography before and after vitrectomy. To evaluate the
      relationship between the effects of vitrectomy and the presence or absence of
      posterior vitreous detachment and/or epimacular membrane, all eyes were placed
      into one of four groups: group A, eyes with posterior vitreous detachment and
      epimacular membrane; B, eyes with posterior vitreous detachment and without
      epimacular membrane; C, eyes without posterior vitreous detachment and with
      epimacular membrane; and D, eyes without posterior vitreous detachment and
      without epimacular membrane. The expression of vascular endothelial growth factor
      and interleukin-6 was investigated immunohistochemically in epimacular membrane
      specimens obtained from seven eyes with diffuse diabetic macular edema. RESULTS:
      The postoperative mean visual acuity (0.653 +/- 0.350: mean +/- SD logarithm of
      minimal angle of resolution [logMAR]) was significantly better than the mean
      preoperative visual acuity (0.891 +/- 0.319 logMAR; Wilcoxon signed-rank test, P
      =.0007). The postoperative foveal thickness (264.5 +/- 118.6 microm) was
      significantly thinner than the preoperative foveal thickness (477.8 +/- 147.7
      microm; Wilcoxon signed-rank test, P <.0001). There were no significant
      differences in the improvement of visual acuity and decrease of foveal thickness
      between the four groups (Kruskal-Wallis test, P =.13, P =.65, respectively). All
      of the epimacular membranes obtained at surgery expressed vascular endothelial
      growth factor and interleukin-6. CONCLUSIONS: These results demonstrated that
      vitrectomy with removal of epimacular membrane is generally an effective
      procedure in reducing diabetic macular edema, and the outcome does not depend on
      the presence absence of posterior vitreous detachment and epimacular membrane.

PMID- 11530051
TI  - Pigment epithelium-derived factor in the vitreous is low in diabetic retinopathy
      and high in rhegmatogenous retinal detachment.
AB  - PURPOSE: To report the levels of pigment epithelium-derived factor in the
      vitreous of patients with diabetic retinopathy, rhegmatogenous retinal
      detachment, and idiopathic macular hole. METHODS: Using enzyme-linked
      immunosorbent assay, we measured the levels of pigment epithelium-derived factor
      in the vitreous of 34 eyes of 33 patients who underwent vitrectomy for the
      treatment of diabetic retinopathy (17 eyes of 16 patients), rhegmatogenous
      retinal detachment (10 eyes), and idiopathic macular hole (seven eyes). RESULTS:
      The vitreal concentration of pigment epithelium-derived factor was 1.15 +/- 0.23
      microg/ml (mean +/- standard error) in eyes with diabetic retinopathy, 3.28 +/-
      0.69 microg/ml in rhegmatogenous retinal detachment, and 1.71 +/- 0.39 microg/ml
      in idiopathic macular hole. The pigment epithelium-derived factor level in
      rhegmatogenous retinal detachment was significantly higher than that in diabetic
      retinopathy (P =.0008) and idiopathic macular hole (P =.034). For eyes with
      diabetic retinopathy, the pigment epithelium-derived factor level was 0.88 +/-
      0.21 microg/ml in proliferative diabetic retinopathy and 2.43 +/- 0.37 microg/ml
      in nonproliferative diabetic retinopathy (P =.0083). Additionally, the pigment
      epithelium-derived factor level in active diabetic retinopathy (0.70 +/- 0.22
      microg/ml) was significantly lower than the level in inactive diabetic
      retinopathy (1.79 +/- 0.35 microg/ml; P =.018). CONCLUSIONS: These results
      suggest that pigment epithelium-derived factor inhibits angiogenesis and that
      lower levels of pigment epithelium-derived factor may be related to the
      angiogenesis in diabetic retinopathy and result in active proliferative diabetic
      retinopathy. The results also suggest that higher levels of pigment epithelium
      derived factor in the eyes with rhegmatogenous retinal detachment may act as a
      neuroprotective agent for the detached retina.

PMID- 11530052
TI  - Massive suprachoroidal hemorrhage during pars plana vitrectomy associated with
      Valsalva maneuver.
AB  - PURPOSE: To report the intraoperative occurrence of massive intraocular
      suprachoroidal hemorrhage associated with Valsalva maneuver. METHODS:
      Retrospective, multicenter study of patients who developed massive choroidal
      hemorrhage associated with Valsalva maneuver during vitrectomy. RESULTS: Massive
      intraoperative suprachoroidal hemorrhage in seven patients (seven eyes) involved
      three men and four women with a median age of 52 years (range, 26 to 82 years).
      General anesthesia was used in six of seven cases. Coughing or "bucking" on the
      endotracheal tube during general anesthesia or severe coughing during the one
      vitrectomy performed under local anesthesia was associated with massive
      suprachoroidal hemorrhage. In five of seven eyes, this occurred near the end of
      surgery, after air-fluid exchange but before sclerotomy closure. Scleral plugs
      were immediately placed, and sclerotomy closure was performed exigently.
      Immediate posterior sclerotomy was performed on five of seven eyes; an additional
      patient underwent posterior sclerotomy postoperatively. After median follow-up of
      18 months (range, 3 to 36 months), final visual acuity was no light perception in
      four eyes, light perception in one eye, 20/250 in one eye, and 20/20 in one eye.
      Four eyes became phthisical. CONCLUSIONS: Valsalva maneuver during pars plana
      vitrectomy may result in massive suprachoroidal hemorrhage with disastrous visual
      consequences. Precautionary measures to prevent coughing or "bucking" on the
      endotracheal tube during general anesthesia, or a prolonged episode of coughing
      during local anesthesia, may prevent this potentially devastating complication.

PMID- 11530053
TI  - Acute effects of sildenafil on the electroretinogram and multifocal
      electroretinogram.
AB  - PURPOSE: To evaluate the acute effects of sildenafil (Viagra; Pfizer, Inc, New
      York, New York) on the electroretinogram and multifocal electroretinogram.
      METHODS: Eighteen healthy individuals (ages 21-49 years) were studied; 14 were
      given 200 mg sildenafil orally and four were given only water. All subjects were
      tested before sildenafil and 1 hour after sildenafil (or water) with a
      desaturated Panel D-15 color test, a full-field standard electroretinogram, and a
      multifocal electroretinogram using the VERIS system; five subjects were also
      tested 5 hours after sildenafil. RESULTS: Responses from the subjects who
      received sildenafil were compared with those from the control subjects. At 1 hour
      after sildenafil, photopic single-flash waveforms were attenuated by 9% and
      scotopic maximal response amplitudes were increased slightly. Photopic and 30-Hz
      flicker electroretinogram responses were delayed; multifocal electroretinogram
      waveforms were delayed (5%-9%) and attenuated (14%-22%) across the posterior
      pole. These changes did not resolve by 5 hours. Nine of the subjects who had
      received sildenafil (64%) reported visual or systemic symptoms, including one who
      reported bluish vision. Ten of those subjects (71%) showed a slight increase in
      color test errors 1 hour after sildenafil. CONCLUSIONS: For at least 5 hours
      after taking 200 mg of sildenafil, cone function was slightly depressed in the
      macula and periphery, as measured by full-field electroretinogram and multifocal
      electroretinogram recordings. However, the affected electroretinogram and
      multifocal electroretinogram parameters still remained within normal limits.

PMID- 11530054
TI  - Rod and cone a-waves in three cases of Bietti crystalline chorioretinal
      dystrophy.
AB  - PURPOSE: To estimate retinal function in Bietti crystalline chorioretinal
      dystrophy using the electroretinogram. METHODS: In this observational case
      series, the scotopic and photopic electroretinograms in three Japanese female
      patients (case 1, 55 years old; case 2, 56 years old; case 3, 47 years old) who
      showed bilateral crystalline retinal deposits but no corneal deposits were
      recorded. The rod and cone a-waves were analyzed by using the method described by
      Hood and Birch (1995, 1997). The parameters Rm(p3) (maximum a-wave amplitude) and
      S (sensitivity) were calculated. RESULTS: In case 1, the rod Rm(p3) was decreased
      in both eyes. The rod S in the right eye was within the normal range, but that in
      the left eye was significantly reduced. Although the cone Rm(p3) was decreased,
      the cone S was within the normal range. In case 2, the rod and cone Rm(p3) was
      reduced, but the rod and cone S was within the normal range in both eyes. In case
      3, the rod and cone Rm(p3) and S were within the normal range. CONCLUSIONS:
      Electroretinograms illustrated different disease stages, however, no eye with
      normal Rm(p3) and decreased S was found in rods and cones. In the early stages of
      this disease, decreased numbers of photoreceptors and/or outer segment shortening
      may be present while phototransduction remains normal. As the damage to the
      retina progresses, phototransduction becomes severely affected. Because reduced
      cone S was not observed in our cases, cones may be less involved than rods in
      this disease.

PMID- 11530055
TI  - International ophthalmology strategic plan to preserve and restore vision-vision
      for the future.

PMID- 11530056
TI  - Laser in situ keratomileusis-induced neurotrophic epitheliopathy.
AB  - PURPOSE: To report two cases of laser in situ keratomileusis-induced neurotrophic
      epitheliopathy with punctate epitheliopathy and rose bengal staining of the
      corneal flap. METHODS: Interventional case reports. RESULTS: A 42-year-old woman
      and a 37-year-old man with no preoperative symptoms or signs of dry eye developed
      dry eye symptoms and bilateral punctate epithelial erosions as well as rose
      bengal staining of the corneal flaps after laser in situ keratomileusis. Neither
      patient had less than 12 mm of wetting with the Schirmer test without anesthesia
      at any time point between development and resolution of the flap surface
      abnormalities. The flap surface abnormalities resolved approximately 6 months
      after laser in situ keratomileusis. CONCLUSIONS: Laser in situ keratomileusis
      induced neurotrophic epitheliopathy may be attributable to loss of trophic
      influence from severed corneal nerve trunks. The condition typically resolves
      approximately 6 months after laser in situ keratomileusis or laser in situ
      keratomileusis retreatment.

PMID- 11530057
TI  - Surgical technique for transcleral-fixation of a dislocated posterior chamber
      intraocular lens.
AB  - PURPOSE: To report a cornea-pars plana through-and-through technique for the
      repositioning and transcleral suture fixation of a dislocated posterior chamber
      intraocular lens. DESIGN: Interventional case series. METHODS: For transscleral
      suture fixation of a dislocated posterior chamber intraocular lens, one needle of
      a double-arm 10-0 Prolene needle is passed through the paracentesis site then
      underneath the intraocular lens haptic, and through the intended scleral outlet
      on the opposite side. The other needle of the Prolene suture is also passed
      through the same paracentesis, above the same haptic, and through the intended
      scleral outlet on the opposite side. The haptic is now well supported, and the
      knot is tied. A similar procedure is performed for the second haptic if
      necessary. RESULTS: Three eyes (three patients) were operated on using this
      technique with good visual and anatomic outcome. CONCLUSION: The described
      technique is simple, safe, allows early visual rehabilitation, and can be
      accomplished without an assistant.

PMID- 11530058
TI  - Posterior ischemic optic neuropathy after uncomplicated cataract extraction.
AB  - PURPOSE: We report a case of posterior ischemic optic neuropathy after
      uncomplicated cataract extraction. DESIGN: Observational case report. METHODS:
      Retrospective description of the natural course of posterior ischemic optic
      neuropathy in one patient seen at an academic institution. RESULTS: The patient
      had sudden vision loss after uncomplicated cataract surgery with the features of
      an optic neuropathy, no acute disk swelling, and delayed optic nerve head
      perfusion on fluorescein angiography. CONCLUSIONS: Posterior ischemic optic
      neuropathy rarely occurs after uncomplicated cataract surgery, and should be
      considered in the setting of postoperative vision loss.

PMID- 11530059
TI  - Asymmetric pigment dispersion in a patient with the unilateral Adie pupil.
AB  - PURPOSE: Pigmentary glaucoma is a bilateral disorder. When it occurs
      asymmetrically or unilaterally, a cause should be sought because it may help us
      to understand the pathophysiology of this condition better. We describe a patient
      with unilateral pigmentary glaucoma and the Adie pupil in the same eye and
      discuss the possible role of the Adie pupil in the development of the pigmentary
      glaucoma. METHODS: A case report. A 37-year-old woman presented with asymmetric
      pigment dispersion resulting in pigmentary glaucoma in the right eye and an
      unilateral Adie pupil in the same eye. RESULTS: We believe that the dilated Adie
      pupil in the right eye might have resulted in a decreased amount of relative
      pupillary block. This, then, might have led to an increased contact between the
      posterior iris and the zonules, resulting in greater pigment dispersion and
      trabecular obstruction in the right eye. CONCLUSION: It has been proposed that
      the pigment is liberated from the iris pigment epithelium because of the
      mechanical rubbing of the posterior iris against the anterior zonular packets.
      Our case supports this proposed mechanism of pigment release.

PMID- 11530060
TI  - Optic disk characteristics before the occurrence of disk hemorrhage in glaucoma
      patients.
AB  - PURPOSE: To evaluate qualitatively the structural characteristics and the
      associated features that antedate the occurrence of a disk hemorrhage in patients
      with glaucoma. METHODS: Retrospective observational case series. A total of 4018
      pairs of stereoscopic optic disk images obtained over 15 years were reviewed. All
      eyes with optic disk images before the occurrence of a disk hemorrhage were
      enrolled. The disk images were evaluated in a masked fashion with respect to the
      general neural rim and peripapillary appearance. RESULTS: The optic disk
      characteristics and associated features that most antedate the disk hemorrhage in
      33 eyes of 26 patients that had previous optic disk images for evaluation are
      focal neural rim notch (36%), thin sloping rim (42%), peripapillary atrophy
      (79%), and superior-inferior rim asymmetry (73%). In eyes with preexisting focal
      rim notches, all subsequent disk hemorrhages were identified at or adjacent to
      the notches. CONCLUSIONS: Focal rim notching may precede the occurrence of a disk
      hemorrhage.

PMID- 11530061
TI  - Glaucoma drainage tube kink after pars plana insertion.
AB  - PURPOSE: To describe focal obstruction of drainage tubes by kinking at the
      scleral entry site after pars plana insertion. METHODS: Case study. RESULTS:
      Three eyes of three patients underwent uncomplicated placement of a Baerveldt
      implant into the vitreous cavity at the time of pars plana vitrectomy.
      Intraocular pressure remained increased after the procedure without evidence of
      flow. Surgical exploration and modification of the tube placement resulted in
      immediate intraocular pressure reduction. Compression of the tube at the scleral
      entry site was confirmed intraoperatively in all eyes by ultrasound
      biomicroscopy. CONCLUSION: Kinking of the tube at its scleral entry site should
      be recognized as a possible cause of increased intraocular pressure without bleb
      formation after pars plana insertion of a glaucoma drainage implant.

PMID- 11530062
TI  - Pupil block glaucoma in phakic and pseudophakic patients after vitrectomy with
      silicone oil injection.
AB  - PURPOSE: To describe pupil block glaucoma in phakic and pseudophakic patients
      after vitrectomy with silicone oil injection. DESIGN: Interventional case series.
      METHODS: Cases were collected from January 1997 to July 2000 from three tertiary
      referral centers. RESULTS: Seven phakic patients (seven eyes) and one
      pseudophakic patient (one eye) presented 1 to 90 days after vitrectomy and
      silicone oil injection with intraocular pressures of 36 to 70 mm Hg. Five
      patients had an observed or potential weakness of the iris-lens diaphragm.
      Treatment with Nd:YAG-laser peripheral iridotomy or inferior iridectomy provided
      a temporary reduction in intraocular pressure for some patients, but all
      eventually required removal of silicone oil. CONCLUSION: Pupil block glaucoma
      after silicone oil injection is well recognized in aphakic patients, but
      ophthalmologists should be aware that it can occur in phakic and pseudophakic
      patients, particularly in complicated cases and patients with a weakness of the
      iris-lens diaphragm.

PMID- 11530063
TI  - Pseudohypopyon of orange pigment overlying a stable choroidal nevus.
AB  - PURPOSE: To report an unusual case of orange pigment pseudohypopyon overlying a
      choroidal nevus. METHODS: Observational case report. A 45-year-old man presented
      with best-corrected visual acuity of 20/25 and metamorphopsia in the right eye
      secondary to localized subfoveal fluid. The detachment displayed a peculiar
      appearance of layered orange pigment, like a pseudohypopyon in its inferior
      aspect. Closer inspection revealed an underlying choroidal nevus and no choroidal
      neovascular membrane. RESULTS: After 31 months of follow-up without treatment,
      the size of the nevus and visual acuity remained stable and metamorphopsia
      continued to resolve as the orange pigment and the subretinal fluid disappeared
      completely. CONCLUSION: An otherwise stable choroidal nevus can display overlying
      clumps of orange pigment and rarely massive accumulation of orange pigment in the
      form of a pseudohypopyon. Orange pigment pseudohypopyon can spontaneously resolve
      with preserved visual acuity.

PMID- 11530064
TI  - Transillumination for accurate placement of radioactive plaques in brachytherapy
      of choroidal melanoma.
AB  - PURPOSE: To present a technique for accurate plaque placement in episcleral
      brachytherapy of choroidal melanoma. METHODS: The tumor margins are marked on the
      scleral surface, and a dummy plaque is temporarily sutured to the globe. A fiber
      optic light pipe is then wedged into the space between the sclera and the plaque.
      Because of the reflecting inner surface of the plaque, the perimeter of the
      plaque can easily be observed during indirect ophthalmoscopy as a circle of light
      surrounding the tumor. By this method, it is possible to determine the exact
      position of the entire plaque in relation to the tumor and make the necessary
      adjustments. When the correct position is found, the dummy plaque is replaced by
      a radioactive plaque. RESULTS: Since 1993, we have routinely used this procedure
      in episcleral brachytherapy. CONCLUSION: This modified transillumination
      technique facilitates a correct positioning of episcleral plaques.

PMID- 11530065
TI  - Bilateral panuveitis: a possible association with Kikuchi-Fujimoto disease.
AB  - PURPOSE: To report a case of necrotizing lymphadenitis caused by Kikuchi-Fujimoto
      disease, which developed bilateral panuveitis. METHODS: A 16-year-old Chinese
      female with histologically proven Kikuchi-Fujimoto disease developed bilateral
      panuveitis 2 years after the onset of lymphadenopathy. RESULTS: Bilateral
      panuveitis was successfully treated with topical steroid. Serologic
      investigations were positive for Epstein-Barr virus antibodies and antinuclear
      antibodies, but no evidence of systemic disease or other causes of ocular
      inflammation was found. CONCLUSION: Kikuchi-Fujimoto disease may be associated
      with intraocular inflammation.

PMID- 11530066
TI  - Progressive outer retinal necrosis and acute retinal necrosis in fellow eyes of a
      patient with acquired immunodeficiency syndrome.
AB  - PURPOSE: To describe an unusual concurrence of acute retinal necrosis and
      progressive outer retinal necrosis in fellow eyes of a patient with acquired
      immunodeficiency syndrome (AIDS). METHODS: Interventional case report. In a 37
      year-old man with AIDS and herpes zoster keratitis in the right eye, progressive
      outer retinal necrosis developed in the right eye and acute retinal necrosis
      developed in the left eye. RESULTS: Disparate presentations of retinitis
      persisted in each eye, and retinal detachment and vision loss ensued in both eyes
      despite antiviral therapy. CONCLUSION: Distinct features of acute retinal
      necrosis and progressive outer retinal necrosis do not necessarily reflect
      systemic factors, and they may be variant manifestations of the same underlying
      infection.

PMID- 11530067
TI  - Central serous chorioretinopathy after epidural corticosteroid injection.
AB  - PURPOSE: To report three patients who developed central serous chorioretinopathy
      after epidural corticosteroid injection for treatment of back pain. DESIGN:
      Interventional case series. METHODS: Three men, aged 73, 52, and 73 years,
      presented with bilateral central serous chorioretinopathy after corticosteroid
      injection in the epidural space for treatment of back pain. In all three cases,
      we did not initially elicit the history of corticosteroid use. RESULTS: Two of
      the three patients, aged 52 and 73 years, had diffuse retinal pigment
      epitheliopathy and one, aged 73 years, had classic central serous
      chorioretinopathy. Two patients had a spontaneous resolution of the subretinal
      fluid in both eyes. One patient had laser photocoagulation in both eyes but
      continued to have diffuse leakage in one eye. CONCLUSIONS: A careful history to
      determine corticosteroid use, including possible intrajoint and epidural
      injection, should be performed in older people with serous detachment of the
      macula, particularly when bilateral.

PMID- 11530068
TI  - Intraocular injection of crystalline cortisone as adjunctive treatment of
      diabetic macular edema.
AB  - PURPOSE: To report the clinical outcome of a diabetic patient with macular edema
      treated with an intravitreal injection of crystalline cortisone. METHODS:
      Interventional case report. A 73-year-old patient with diabetes mellitus
      presented with clinically significant diffuse macular edema caused by
      nonproliferative diabetic retinopathy. Despite grid laser coagulation in the
      macular region, cystoid macular edema progressed, and within 6 months before the
      cortisone injection, visual acuity declined from 0.25 to 0.16 and, finally, to
      0.10. The patient received a single intravitreal injection of triamcinolone
      acetonide with topical anesthesia. RESULTS: After the intravitreal injection of
      triamcinolone acetonide, visual acuity improved from 0.10 to 0.40 during the
      follow-up period spanning 5 months. Intraocular pressure increased to values up
      to 30 mm Hg before antiglaucomatous treatment. CONCLUSION: Intravitreal injection
      of triamcinolone acetonide may be useful for treatment of diabetic macular edema
      resistant to conventional therapy.

PMID- 11530069
TI  - Upregulation of pigment epithelium-derived factor after laser photocoagulation.
AB  - PURPOSE: To determine the changes in the expression of pigment epithelium-derived
      factor in cultured human retinal pigment epithelial cells and rat retinas after
      laser photocoagulation. METHODS: Experimental study of laser photocoagulation on
      human retinal pigment epithelial cells in culture and on adult rats. Reverse
      transcription-polymerase chain reaction and semiquantitative polymerase chain
      reaction analysis were used. RESULTS: After photocoagulation, the mRNA expression
      of pigment epithelium-derived factor was upregulated in human retinal pigment
      epithelial cells at 6 hours and then gradually decreased. Compared with controls,
      significantly higher levels of pigment epithelium-derived factor were observed in
      rat retinas from 6 to 24 hours after laser photocoagulation (P <.005), and they
      were still higher than before photocoagulation at 2 weeks. CONCLUSION: An
      upregulation of pigment epithelium-derived factor in retinal pigment epithelial
      cells and in the retina after photocoagulation suggests that pigment epithelium
      derived factor plays a role in inhibiting neovascularization by its
      antiangiogenic activity.

PMID- 11530070
TI  - Hypotony caused by scleral buckle erosion in Marfan syndrome.
AB  - PURPOSE: To describe hypotony caused by erosion of the conjunctiva and sclera by
      a silicone scleral buckle. METHODS: Interventional case report. A 33-year-old man
      with Marfan syndrome presented with hypotony maculopathy and a collapsed globe 17
      months after repair of retinal detachment with a silicone sponge and silicone
      encircling band. RESULTS: Examination in the operating room revealed extrusion of
      the buckle through the conjunctiva and full-thickness scleral erosion. The
      silicone buckle was removed, and the scleral defect was closed with interrupted 8
      0 nylon sutures. Postoperative glaucoma was treated with cyclophotocoagulation.
      Eight months after scleral repair, visual acuity was RE: 20/40, intraocular
      pressure was 10 mm Hg, and the retina was attached. CONCLUSION: Full-thickness
      scleral erosion secondary to a silicone exoplant causing hypotony is a rare long
      term complication in patients with thin sclera.

PMID- 11530071
TI  - Indocyanine green-assisted peeling of the internal limiting membrane may cause
      retinal damage.
AB  - PURPOSE: To demonstrate possible retinal damage caused by indocyanine green dye
      for staining of the internal limiting membrane in surgery for idiopathic macular
      hole. METHODS: Consecutive interventional case series. We report on the
      ultrastructural findings of the internal limiting membrane in 10 eyes of 10
      patients. RESULTS: All specimens revealed not only the internal limiting
      membrane, but also some small amounts of retinal elements, such as the plasma
      membrane of Muller cells and other undetermined structures. This indicates a
      cleavage plane not exactly at the inner undulating aspect of the internal
      limiting membrane but within the innermost retinal layers. CONCLUSION: Dilutions
      of indocyanine green as recommended in the literature may alter the structure of
      the retina to some degree. Possible factors responsible for this inadvertent
      action may include (1) concentration, (2) osmolarity pH, (3) time of tissue
      contact, and (4) mechanical factors from more forceful traction during peeling.
      Although functional consequences of these findings remain unclear as yet, factors
      that may induce damage to the innermost retina should be elucidated.

PMID- 11530072
TI  - Indocyanine green effect on cultured human retinal pigment epithelial cells:
      implication for macular hole surgery.
AB  - PURPOSE: To evaluate potential toxic effects of indocyanine green dye on cultured
      human retinal pigment epithelial cells. METHODS: Controlled laboratory
      experiment. Cultured human retinal pigment epithelial cells were exposed to
      balanced saline solution, balanced saline solution with endoillumination,
      indocyanine green or indocyanine green with endoillumination. Cells were
      evaluated by light microscopy, electron microscopy, and a mitochondrial
      dehydrogenase assay. RESULTS: Retinal pigment epithelial cells exposed to
      indocyanine green showed no histologic or ultrastructural changes. Those exposed
      to indocyanine green alone or indocyanine green plus light demonstrated a
      significant decrease in mitochondrial enzyme activity (P = 0.0002 and 0.005,
      respectively). CONCLUSION: Brief exposure of cultured human retinal pigment
      epithelial cells to indocyanine green results in decreased mitochondrial enzyme
      activity but does not appear to influence cellular morphology or ultrastructure.

PMID- 11530073
TI  - Vitreoretinal surgery for a subretinal hydatid cyst.
AB  - PURPOSE: To report the vitreoretinal surgery for management of a subretinal
      hydatid cyst. METHODS: Conventional pars plana vitrectomy was performed for the
      removal of a subretinal hydatid cyst and treatment of retinal detachment in the
      right eye (RE) of a 34-year-old woman. The cyst content was aspirated by a flute
      needle after retinotomy and cystotomy. The cyst wall was separated from overlying
      retina and removed. The retina was attached by liquid perfluorocarbon and
      silicone oil. Postoperatively, the patient was followed for 15 months. RESULTS:
      After vitreoretinal surgery, the retina RE was attached and recurrence of hydatid
      disease was not seen in vitreous cavity or subretinal space during the follow-up
      period. Visual acuity increased from counting fingers to 20/63 at the end of the
      follow-up time. CONCLUSION: A subretinal hydatid cyst that causes retinal
      detachment may be treated effectively with vitreoretinal surgery.

PMID- 11530074
TI  - Role of Fas-ligand in age-related maculopathy not established.
AB  - PURPOSE: Fas-ligand expression on retinal pigment epithelium is hypothesized to
      have an inhibitory effect on human ocular neovascularization. METHODS: We studied
      Fas-ligand expression in the aging retinal pigment epithelium and in early and
      late stages of age-related maculopathy. Immunohistochemistry with antibodies
      against Fas-ligand was performed on paraffin-embedded sections of 23 human eye
      bank eyes (aged 45 to 96 years) and 12 eyes with exudative age-related
      maculopathy. RESULTS: Fas-ligand expression in retinal pigment epithelium was not
      related to age or to the presence of early age-related maculopathy. Furthermore,
      Fas-ligand expression in retinal pigment epithelium was similar in subretinal and
      subretinal pigment epithelium choroidal neovascular membranes. CONCLUSION: It
      appears to be unlikely that Fas-ligand expressed on retinal pigment epithelium
      controls the extension of choroidal neovascular membranes from subretinal pigment
      epithelium to subretinal.

PMID- 11530075
TI  - Choroidal neovascularization associated with aplasia of the optic nerve.
AB  - PURPOSE: To report an unusual case of unilateral aplasia of the optic nerve
      associated with choroidal neovascularization. DESIGN: Observational case report.
      METHODS: In a 29-year-old female with optic nerve aplasia of the right eye and no
      choroidal neovascularization at age 23 years, choroidal neovascularization of the
      right eye was present by ophthalmoscopy and fluorescein angiography. RESULTS:
      Fluorescein angiography disclosed de novo choroidal neovascularization
      corresponding to fibrovascular proliferation evident on ophthalmoscopy at age 29
      years. CONCLUSION: Choroidal neovascularization may develop de novo during adult
      life in an eye with optic nerve aplasia.

PMID- 11530076
TI  - Peripheral homonymous scotomas from a cavernous angioma affecting fibers
      subserving the intermediate region of the striate cortex.
AB  - PURPOSE: To report the case of a pure peripheral homonymous visual field defect
      and to delineate the representation of the visual field on the striate cortex.
      METHODS: Observational case report. Neuro-ophthalmologic and neuroimaging
      assessment of a patient with a cavernous angioma of the right parieto-occipital
      lobe. RESULTS: The patient had left homonymous scotomas located 40 degrees to 60
      degrees from the vertical meridian. Neuroimaging indicated that the lesion was
      affecting the optic radiations at their termination in the intermediate portion
      of the striate cortex or the striate cortex itself. CONCLUSION: Homonymous field
      defects are typically located within 10 degrees of fixation. This patient had a
      peripheral homonymous field defect from damage to the intermediate striate
      cortex. Correlation of the neuroimaging findings in this case with the most
      commonly used maps of the representation of the visual field on the striate
      cortex suggests that none of the maps correctly predicts the location or extent
      of lesions that affect the intermediate portion of the cortex.

PMID- 11530077
TI  - Localization of post-traumatic trochlear nerve palsy associated with hemorrhage
      at the subarachnoid space by magnetic resonance imaging.
AB  - PURPOSE: To report evaluation of traumatic trochlear nerve palsy using head
      magnetic resonance imaging. DESIGN: Observational case reports. METHODS: We
      examined two cases involving trochlear nerve palsy after closed head injury.
      RESULTS: Using a fluid attenuated inversion recovery pulse sequence, MRI showed a
      high-intensity lesion consistent with subarachnoid hemorrhage at the trochlear
      nerve area in the ambient cisterns. CONCLUSION: An impact force directed toward
      the tentorium can be a mechanism of injury in some post-traumatic trochlear nerve
      palsies. Fluid attenuated inversion recovery pulse sequence is a sensitive method
      for detection of abnormalities in cases associated with head injury.

PMID- 11530091
TI  - Optical coherence tomography of tractional macular elevations in eyes with
      proliferative diabetic retinopathy.
AB  - PURPOSE: To document the findings of optical coherence tomography in eyes with
      tractional macular elevation associated with proliferative diabetic retinopathy,
      paying special attention to differentiating between tractional retinal detachment
      and retinoschisis. DESIGN: Observational case series. METHODS: We retrospectively
      reviewed images of optical coherence tomography obtained from 17 consecutive eyes
      (17 patients) with proliferative diabetic retinopathy without vitreous opacity
      and showing tractional macular elevation with or without foveal involvement.
      RESULTS: Tractional retinal detachment and retinoschisis could be differentiated
      in the cross-sectional images of optical coherence tomography. Retinoschisis with
      or without associated retinal detachment was observed in 16 of 17 eyes (94%),
      whereas retinal detachment was observed in only six of 17 eyes (35%). Five eyes
      showed both findings of retinal detachment and retinoschisis. CONCLUSIONS:
      Optical coherence tomography is useful for distinguishing tractional
      retinoschisis from retinal detachment in eyes with proliferative diabetic
      retinopathy and macular elevation. Tractional retinoschisis with or without
      retinal detachment is the most frequent pattern of tractional macular elevation
      in eyes with proliferative diabetic retinopathy.

PMID- 11530092
TI  - The evolution of the coronary care unit.

PMID- 11530093
TI  - Life out of balance: the sympathetic nervous system and cardiac arrhythmias.

PMID- 11530094
TI  - LQT genotype-phenotype relationships: patients and patches.

PMID- 11530095
TI  - Measuring electrophysiological changes in transgenic mouse models of
      cardiovascular disease.

PMID- 11530096
TI  - Diazoxide induced cardioprotection: what comes first, K(ATP) channels or reactive
      oxygen species?

PMID- 11530097
TI  - Heat shock proteins and cardiac protection.
AB  - The heat shock proteins (hsps) are expressed in normal cells but their expression
      is enhanced by a number of different stresses including heat and ischaemia. They
      play important roles in chaperoning the folding of other proteins and in protein
      degradation. In the heart a number of studies have shown that prior induction of
      the hsps by a mild stress has a protective effect against a more severe stress.
      Moreover, over-expression of an individual hsp in cardiac cells in culture or in
      the intact heart of either transgenic animals or using virus vectors, also
      produces a protective effect, directly demonstrating the ability of the hsps to
      produce protection. These findings indicate the potential importance of
      developing procedures for elevating hsp expression in a safe and efficient manner
      in human individuals using either pharmacological or gene therapy procedures.

PMID- 11530098
TI  - Atrial natriuretic peptides in pathophysiological diseases.

PMID- 11530099
TI  - Long-term electrophysiological effects of regional cardiac sympathetic
      denervation of the neonatal dog.
AB  - OBJECTIVE: In many cardiac arrhythmias, both a triggering factor and a favorable
      myocardial substrate are required. Whereas the sympathetic nervous system may
      trigger tachyarrhythmias, its function as a long-term modulator of the myocardial
      substrate is less well understood. Therefore, we tested the hypothesis that
      regional sympathetic denervation at birth would produce an abnormal myocardial
      substrate. The comparator was the substrate associated with inherited, lethal
      tachyarrhythmias at 5 months of age in German shepherd dogs with incomplete
      sympathetic innervation. METHODS: Mongrel dogs underwent right cardiac
      stellectomy (RSX) within the first day of life and were terminally studied with
      control littermates at 5 months of age. RESULTS: On days 1-21 of life, RSX
      animals manifested significant QT prolongation on ECG and sudden, asystolic
      death. Beyond this age, QT intervals normalized and deaths did not occur. At 5
      months, action potentials (AP) were recorded from Purkinje fibers (PF) and
      midmyocardial preparations in anteroseptal (AS) and posterobasal (PB) left
      ventricle. Early afterdepolarizations occurred only in left ventricular PF from
      RSX dogs. Isoproterenol prolonged AP duration in AS and shortened it in PB of RSX
      but not control dogs. The incidence of isoproterenol-initiated triggered activity
      and the amplitude of delayed afterdepolarizations were greater in RSX than
      control dogs. CONCLUSION: Five months after RSX heterogeneous alterations of LV
      electrophysiological properties were similar to those previously observed in
      animals having inherited deficits in sympathetic innervation and sudden death.
      This implicates the sympathetic nerves as long-term modulators of an
      arrhythmogenic substrate. That 5-month-old RSX dogs did not experience
      tachyarrhythmias or sudden death indicates that further anomalies--beyond those
      explicable by the substrate change--must exist to induce sudden death.

PMID- 11530100
TI  - A spectrum of functional effects for disease causing mutations in the Jervell and
      Lange-Nielsen syndrome.
AB  - OBJECTIVE: Jervell and Lange-Nielsen syndrome (JLNS) is a recessively inherited
      long QT syndrome (LQTS) characterised by profound sensorineural deafness and
      predisposition to syncope and sudden cardiac death. Mutation analysis has
      established the presence of mutations in affected individuals in the genes KCNQ1
      and KCNE1: the potassium channel complex responsible for the cardiac I(Ks)
      current involved in repolarisation of the ventricular action potential. Our
      objective was to determine the functional effects of disease causing mutations in
      JLNS. METHODS: In this study we have investigated the electrophysiological
      effects of eight distinct JLNS mutations after expression of cRNA in Xenopus
      laevis oocytes. RESULTS: KCNE1 mutant T59P/L60P showed no dominant negative
      effect and was a pure loss of function mutation. KCNQ1 mutant E261D showed a
      strong dominant-negative effect. KCNQ1 mutant R243H produced a moderate dominant
      negative effect, right shifted the steady-state activation curve and led to an
      increased deactivation rate. The behaviour of KCNQ1 mutants 572-576del, 1008delC,
      R518X, Q530X, R594Q depended on the relative quantities of mutant and wild-type
      proteins (with a weak dominant-negative effect present at 1:3 but not 1:1
      injection ratios). These data indicate the presence of an additional assembly
      domain before S2-S3 and the importance of the S4-S5 region in channel function
      and gating. CONCLUSIONS: Our data suggest a spectrum of behaviour for disease
      causing mutations from simple loss of function through to prominent dominant
      negative behaviour.

PMID- 11530101
TI  - High resolution optical mapping reveals conduction slowing in connexin43
      deficient mice.
AB  - Analysis of mice with genetically altered expression of cardiac connexins can
      provide insights into the role of individual gap junction channel proteins in
      cell-to-cell communication, impulse propagation, and arrhythmias. However,
      conflicting results have been reported regarding conduction velocity slowing in
      mice heterozygous for a null mutation in the gene encoding connexin43 (Cx43).
      METHODS: High-resolution optical mapping was used to record action potentials
      from 256 sites, simultaneously, on the ventricular surface of Langendorff
      perfused hearts from 15 heterozygous (Cx43+/-) and 8 wildtype (Cx43+/+) mice
      (controls). A sensitive method for measuring epicardial conduction velocity was
      developed to minimize confounding influences of subepicardial breakthrough and
      virtual electrode effects. RESULTS: Epicardial conduction velocity was
      significantly slower (23 to 35%, P<0.01) in Cx43+/- mice compared to wildtype.
      There was no change in conduction patterns or anisotropic ratio (Cx43+/- 1.54+/
      0.33; Cx43+/+ 1.57+/-0.17) suggesting that Cx43 expression was reduced uniformly
      throughout myocardium. The magnitude of reductions in conduction velocity and
      Cx43 protein expression (45%) were similar in mice in which the null allele
      occurred in a pure C57BL/6J genetic background versus a mixed (C57BL/6J X 129)
      background. Action potential duration did not differ between mice of different
      genotypes. CONCLUSIONS: A approximately 50% reduction of Cx43 expression causes
      significant conduction velocity slowing in the Cx43+/- mouse heart. The apparent
      lack of conduction velocity changes reported in previous studies may be related
      to technical factors rather than variations in genetic background. High
      resolution optical mapping is a powerful tool for investigating molecular
      determinants of propagation and arrhythmias in genetically engineered mice.

PMID- 11530102
TI  - Mitochondrial K(ATP) channel opening protects a human atrial-derived cell line by
      a mechanism involving free radical generation.
AB  - OBJECTIVES: The mechanism by which the mitochondrial K(ATP) channel openers
      confer protection against ischemia/reperfusion injury is debated. Evidence
      suggests that rather than solely being an end effector, opening of these channels
      may act by a trigger mechanism. We examined the effects of the mitochondrial
      K(ATP) channel opener, diazoxide on parameters of mitochondrial function with
      specific reference to reactive oxygen species (ROS) generation in a human atrial
      derived cell line model of simulated ischemia/reperfusion (LSI/R). METHODS AND
      RESULTS: Propidium iodide (PI) exclusion was used to assess survival. Diazoxide
      treatment conferred protection against LSI/R (13.9+/-0.9% vs. 36.9+/-4.5%
      controls) that was abolished by pre-treatment with the mitoK(ATP) channel
      blocker, 5-hydroxydecanoate (5-HD) (33.3+/-3.6%) and with the free radical
      scavenger, 2-mercaptopropionylglycine (MPG) (29+/-4.0%). Diazoxide caused
      increased oxidation of the ROS probe, reduced mitotracker orange (1.3 vs. 1.0
      arbitrary units for control; P<0.01 vs. control) that was abrogated by either 5
      HD or MPG (1.07 and 1.07 arbitrary units, respectively). At the same time there
      was no change in orange fluorescent signal from the membrane potential sensitive
      probe, JC-1 indicating no change in mitochondrial membrane potential. Changes in
      light scattering, reflecting changes in mitochondrial volume, occurred during
      treatment with diazoxide. CONCLUSION: These results demonstrate for the first
      time that the mitoK(ATP) channel opener diazoxide can act as a trigger of
      preconditioning by a mechanism involving mitochondrial swelling and the
      generation of ROS.

PMID- 11530103
TI  - Role of adenosine in ischemic preconditioning in rats depends critically on the
      duration of the stimulus and involves both A(1) and A(3) receptors.
AB  - OBJECTIVES: There is currently general agreement that adenosine is not involved
      in ischemic preconditioning (IP) in rat hearts. We hypothesized that the failure
      to show a role for adenosine is due to the use of brief preconditioning stimuli,
      and therefore investigated whether adenosine is involved when longer stimuli are
      employed and which receptor subtypes are involved. METHODS AND RESULTS: Infarct
      size (IS) was determined in anesthetized rats after 180 min of reperfusion (REP)
      following a 60-min coronary artery occlusion (CAO). IS was 69+/-2% (n=15) of the
      risk area in control rats and 45+/-2% (n=19; P<0.05) following IP by a single 15
      min CAO. The non-selective adenosine receptor antagonist SPT, which itself had no
      effect on IS (74+/-1%), blunted the protection by IP (IS=57+/-2%, P<0.05) in a
      dose of 2 x 5 mg/kg i.v., and abolished the protection (IS=70+/-1%) at 2 x 25
      mg/kg i.v. Following IP by three cycles of 3-min CAO and 3-min REP, IS was 24+/
      6% (P<0.05), which was not affected by SPT in doses of 2 x 10 and 2 x 25 mg/kg
      i.v. The A(3) antagonist MRS-1191 (3.3 mg/kg, i.p.), which itself did not affect
      IS (70+/-2%), blunted the protection by IP with a 15-min CAO (IS=54+/-2%,
      P<0.05). When 2 x 5 mg/kg SPT (a dose selective for A(1)-receptors, as it did not
      affect the protection by the A(3) selective agonist IB-MECA, 51+/-3%) and MRS
      1191 were combined the protection by IP was abolished (IS=67+/-2%). CONCLUSIONS:
      Involvement of adenosine in IP in rats depends critically on the duration of the
      stimulus. Thus, whereas adenosine was not involved when stimuli of 3-min duration
      were employed, activation of both A(1) and A(3) receptors contributed when a
      stimulus of 15 min was used.

PMID- 11530104
TI  - Accumulation of molecules involved in alpha1-adrenergic signal within caveolae:
      caveolin expression and the development of cardiac hypertrophy.
AB  - OBJECTIVE: Caveolin, a major protein component of caveolae, is now considered to
      be an inhibitor of cellular growth and proliferation. In this study, we examined
      the localization of the molecules involved in alpha1-adrenergic receptor signal
      relative to that of caveolin in the heart and the changes in caveolin expression
      during the development of hypertrophy in SHR. METHODS: We purified the caveolar
      protein fractions from rat cardiac tissues, H9C2 cells, and rat vascular smooth
      muscle cells. Using radioligand receptor binding assay and immunoblot analysis,
      we examined the distribution and the amount of alpha1-AR and caveolin. RESULTS:
      Caveolin-3, the alpha1-adrenergic receptor, Gq and PLC-beta subtypes (PLC-beta1, 
      beta3) were found exclusively in the caveolar fraction in the above tissues.
      Caveolin-3 were co-immunoprecipitated with alpha1-adrenergic receptor and Gq from
      the cardiac tissues. The amount of caveolin subtypes expression (caveolin-1 and 
      3) and the amount of the alpha1-adrenergic receptor were examined in the hearts
      of SHR and age-matched WKY (4- and 24-weeks-old). The amount of caveolin-3
      expression was significantly smaller in SHR at 24-weeks-old than that in SHR at 4
      weeks-old and that in WKY at 24-weeks-old. CONCLUSIONS: The molecules involved in
      alpha1-adrenergic signaling are confined to the same microdomain as caveolin. A
      decrease in caveolin-3 expression may play a role in the development of cardiac
      hypertrophy in SHR, presumably through de-regulating the inhibition of growth
      signal in the hearts of SHR in the hypertrophic stage.

PMID- 11530105
TI  - Enhanced protein phosphorylation in hypertensive hypertrophy.
AB  - OBJECTIVE: Chronic pressure overload in spontaneously hypertensive rats (SHR) is
      accompanied by heart hypertrophy and signs of heart failure. Since there is
      growing evidence for a possible pathophysiological role of altered protein
      phosphorylation in heart hypertrophy and failure, we studied here cardiac
      regulatory phosphoproteins and the kinases and phosphatases which regulate their
      phosphorylation state. METHODS: The experiments were performed in ventricles of
      SHR (12-13 weeks old) and age-matched normotensive Wistar-Kyoto rats (WKY).
      RESULTS: Basal as well as isoproterenol (Iso)-stimulated force of contraction
      (FOC) was markedly decreased in isolated electrically driven papillary muscles of
      SHR. Iso (3 micromol/l, 10 min) increased FOC by 0.91+/-0.20 mN in SHR and by
      3.88+/-0.52 mN in WKY, respectively. Ca(2+)-uptake by sarcoplasmic reticulum (SR)
      at low ionized Ca(2+)-concentration was increased in homogenates from SHR. This
      was not due to altered expression of phospholamban (PLB), SR-Ca(2+)-ATPase and
      calsequestrin. However, PLB-phosphorylation at threonine-17 (PLB-PT-17) and the
      activity of Ca(2+)/calmodulin dependent protein kinase (Ca(2+)/Cam-PK) was
      increased in SHR. In addition, we found an enhanced protein kinase A (PKA)
      dependent phosphorylation of the inhibitory subunit of troponin (TnI). In
      contrast, there was no difference in the activity or expression (protein- and
      mRNA-level) of protein phosphatases type 1 or type 2A between SHR and WKY.
      CONCLUSIONS: It is suggested that increased Ca(2+)/Cam-PK-activity with resulting
      increase of PLB-PT-17 enhanced SR-Ca(2+)-uptake in SHR and might contribute to
      the pathophysiological changes in cardiac hypertrophy of SHR.

PMID- 11530106
TI  - The volume-dependency of parallel conductance throughout the cardiac cycle and
      its consequence for volume estimation of the left ventricle in patients.
AB  - OBJECTIVE: To study the hypothesis that the electrical conductance of tissues and
      fluids (parallel conductance (G(p))) around the ventricle depends on left
      ventricular volume throughout the cardiac cycle. METHODS: We extended a recently
      developed method to determine G(p) throughout the cardiac cycle. First, we
      compared the estimates of parallel conductances obtained with the new method
      (G(a)(p)) with those of the conventional one (G(1)(p)), both averaged over the
      cardiac cycles. Secondly, G(a)(p) was determined throughout the cardiac cycle and
      its volume dependency was assessed. Thirdly, the factor alpha was calculated as
      the ratio between stroke volume, obtained by the conductance method using
      G(1)(p), and that obtained by a thermodilution method. Because the non
      homogeneous field was indicated to be the reason for the dependency of G(p) on
      left ventricular volume as well as for the need for alpha, we tested whether the
      hypothesis implies that a correction with alpha is not needed if G(p) is
      determined throughout the cardiac cycle. RESULTS: We found a negative linear
      relation between G(p) and left ventricular volume. This relation appeared to be
      reproducible within each patient. Furthermore, we found that alpha deviates from
      1 primarily due to the dependency of G(p) on left ventricular volume. CONCLUSION:
      To obtain stroke volume or to determine absolute left ventricular volume
      continuously within a cardiac cycle, G(p) should be determined throughout each
      cardiac cycle and if a constant G(p) throughout the cardiac cycle is used a
      correction with the factor alpha should be made to correct for a possible
      influence of electrical field heterogeneity.

PMID- 11530107
TI  - Antioxidant vitamins prevent cardiomyocyte apoptosis produced by norepinephrine
      infusion in ferrets.
AB  - BACKGROUND: Norepinephrine (NE) induces apoptosis in cultured neonatal rat
      myocytes. To determine whether this change occurred in intact animals after
      chronic subhypertensive doses of NE, and whether the effect was mediated via
      oxidative stress produced by NE, we measured myocyte apoptosis and apoptotic gene
      proteins in ferrets receiving chronic NE with and without antioxidant vitamin
      treatment. METHODS: Ferrets were administered either subcutaneous NE or vehicle
      and simultaneously assigned to receive antioxidant vitamins (beta-carotene,
      ascorbic acid and alpha-tocopherol) or vehicle for 4 weeks. Resting hemodynamics
      and plasma NE were measured at 4 weeks. Animals were then sacrificed for
      measuring cardiac myocyte size by electron microscopy, and oxidative stress by
      reduced to oxidized glutathione (GSH/GSSG) ratio and mitochrondrial DNA 8-oxo-7,8
      dihydro-2'-deoxyguanosine (8-oxo-dG). Cardiomyocyte apoptosis was detected by
      both terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling
      (TUNEL) assay and monoclonal antibody to single-stranded DNA (Mab) staining.
      Western blot analysis was used to measure the expression of the antiapoptotic
      protein Bcl-2 and apoptotic protein Bax. RESULTS: NE administration produced a 4
      fold increase in plasma NE, but had no effect on resting heart rate, heart
      weight, arterial pressure, left ventricular systolic function or cardiac cell
      size. NE infusion decreased tissue GSH/GSSG ratio, and increased mtDNA 8-oxo-dG,
      and TUNEL- and Mab-positive apoptotic cells. These changes were associated with a
      27% decrease in Bcl-2 protein, a 42% increase in Bax and a 57% reduction in the
      ratio of Bcl-2/Bax. All of the changes were prevented by co-administration of
      antioxidant vitamins. CONCLUSION: NE administration at a dose which produced no
      significant increase in blood pressure or myocyte hypertrophy caused
      cardiomyocyte apoptosis in intact animals. This effect was associated with an
      increase in oxidative stress, up-regulation of Bax protein and down-regulation of
      Bcl-2 protein. Antioxidant vitamins prevented the changes produced by NE. The
      findings suggest that NE-induced myocyte apoptosis is mediated by oxidative
      stress, and that antioxidant vitamins may be beneficial in heart failure in which
      cardiac NE release is increased.

PMID- 11530108
TI  - Fas ligand/Fas-mediated apoptosis in human coronary artery smooth muscle cells:
      therapeutic implications of fratricidal mode of action.
AB  - OBJECTIVE: This study aimed to determine the mode of action of Fas ligand
      (FasL)/Fas at mediating apoptosis so as to evaluate the potential of FasL in gene
      therapy for restenosis. METHODS: Passaged human coronary artery smooth muscle
      (HCASM) cells were infected with recombinant adenoviral vectors expressing murine
      FasL. Various parameters of FasL expression and apoptosis were measured using
      FACS, immunofluorescence, calorimetric, and cytotoxicity assays. RESULTS: Most
      HCASM cells under normal growth conditions expressed Fas and were shown to be
      susceptible to membrane bound but not soluble FasL. However, some FasL expressing
      cells survived for up to 7 days. These surviving cells were observed to be
      spatially distributed and were not in direct physical contact with each other.
      Upon examination, it was determined that although the majority of the surviving
      cells expressed FasL, only 30% expressed both Fas and FasL. These cells were
      capable of inducing apoptosis of target cells and some were also susceptible to
      FasL expressing cells, provided that the effector and target cells were in close
      physical contact. FasL/Fas-mediated apoptosis was inhibited by p35, a baculovirus
      gene that inhibits caspases. Additionally, in contrast to HCASM cells, neither
      membrane-bound nor soluble FasL induced apoptosis in coronary artery endothelial
      cells. CONCLUSIONS: FasL expressing HCASM cells do not undergo FasL/Fas mediated
      "suicide" but kill neighboring cells bearing Fas in a "fratricidal" manner. A
      small population of HCASM cells expresses no surface Fas. These results imply
      that HCASM cells transduced in vivo with FasL may serve as "scavengers" and exert
      a bystander effect on surrounding cells that may be enhanced by co-expression of
      p35. As FasL-mediated apoptosis occurs in coronary arterial smooth muscle but not
      endothelial cells, FasL may also offer an advantage over other genes for use in
      restenosis since the latter may indiscriminately delay re-endothelialization at
      the sites of gene.

PMID- 11530109
TI  - Coronary vasa vasorum neovascularization precedes epicardial endothelial
      dysfunction in experimental hypercholesterolemia.
AB  - OBJECTIVE: Experimental hypercholesterolemia is associated with vasa vasorum
      neovascularization, unknown to occur before or after initial lesion formation.
      Thus, this study was performed to determine the temporal course of
      neovascularization of coronary vasa vasorum in relation to endothelial
      dysfunction, a hallmark of early atherosclerosis. METHODS: Female domestic pigs
      were fed a normal diet (Group 1), a hypercholesterolemic diet for 2 and 4 weeks
      (Group 2), or a hypercholesterolemic diet for 6 and 12 weeks (Group 3). In vitro
      analysis of relaxation response to bradykinin served as an index for epicardial
      endothelial function. Spatial pattern and density of coronary vasa vasorum were
      assessed by three-dimensional microscopic computed tomography. RESULTS:
      Relaxation response of coronary arteries to bradykinin was normal in both Group 1
      (93+/-6%) and Group 2 (89+/-7%) but impaired in Group 3 (71+/-11%; P<0.05 vs.
      Group 1 and 2). In contrast, density of coronary vasa vasorum was significantly
      higher in both Group 2 (4.88+/-2.45 per-mm(2)) and Group 3 (4.50+/-1.37 per
      mm(2)) compared to Group 1 (2.97+/-1.37 per-mm(2); P<0.05 vs. Group 2 and 3).
      CONCLUSION: This study demonstrates that coronary vasa vasorum neovascularization
      occurs within the first weeks of experimental hypercholesterolemia and prior to
      the development of endothelial dysfunction of the host vessel, suggesting a role
      for vasa vasorum neovascularization in the initial stage of atherosclerotic
      vascular disease.

PMID- 11530110
TI  - Interaction between cholinergic and nitrergic vasodilation: a novel mechanism of
      blood pressure control.
AB  - OBJECTIVE: Cholinergic vasodilation has been thought to play little if any role
      in the regulation of blood pressure in humans. Autonomic denervation potentiates
      the vasoconstriction evoked by nitric oxide synthase inhibition in humans, but
      the mechanism is unclear. We hypothesized that this may be related to loss of
      neuronal, non-nitric-oxide-dependent vasodilation. METHODS: To test this
      hypothesis, we examined effects of cholinergic blockade on blood pressure, heart
      rate and peripheral vascular responses to systemic infusion of the nitric-oxide
      dependent vasoconstrictor L-NMMA (0.5 mg/kg/min over 15 min) in eight normal
      subjects. RESULTS: The L-NMMA-induced increase in mean (+/-S.E.) arterial
      pressure was roughly three times larger (P=0.002) in the presence than in the
      absence of cholinergic blockade (38+/-6 vs. 13+/-2 mmHg). Similarly, the increase
      in systemic and calf vascular resistance was more than twofold larger during L
      NMMA-atropine. This potentiation was specific for nitric-oxide-dependent
      vasoconstriction, because atropine did not alter the responses to phenylephrine
      infusion. Cholinergic blockade also altered (P=0.004) the heart rate response to
      nitric oxide synthase inhibition; during L-NMMA alone heart rate decreased by
      10+/-2 beats/min, whereas during L-NMMA-atropine infusion it increased by 14+/-4
      beats/min. CONCLUSION: Cholinergic mechanisms play an important hitherto
      unrecognized role in offsetting the hypertension and cardiac sympathetic
      activation caused by nitric oxide synthase inhibition in humans. Decreased
      parasympathetic activity and impaired nitric oxide synthesis characterize several
      cardiovascular disease states, as well as normal aging. The conjunction of these
      two defects could trigger sudden death and contribute to the hypertension of the
      elderly.

PMID- 11530111
TI  - Genetic augmentation of nitric oxide synthase increases the vascular generation
      of VEGF.
AB  - OBJECTIVE: Vascular endothelial growth factor (VEGF) induces the release of
      nitric oxide (NO) from endothelial cells. There is also limited data suggesting
      that NO may enhance VEGF generation. METHODS: To further investigate this
      interaction, we examined the effect of exogenous and endogenous NO on the
      synthesis of VEGF by rat and human vascular smooth muscle cells (VSMC) by
      exposing cells to exogenous NO donors, or to genetic augmentation of eNOS or
      iNOS. RESULTS: NO-donors potentiated by 2-fold the generation of VEGF protein by
      rat or human VSMC. Similarly, rat or human VSMC transiently transfected with
      plasmid DNA encoding eNOS or iNOS, synthesized up to 3-fold more VEGF than those
      transfected with control plasmid DNA, an effect which was reversed after
      treatment with the NOS antagonist L-NAME. Rat VSMC stably transfected with pKeNOS
      plasmid, constitutively produced NO and released high concentrations of VEGF. In
      these cells, L-NAME significantly reduced NO synthesis and decreased VEGF
      generation. The VEGF protein produced by NOS-transfected VSMC was biologically
      active, as conditioned media harvested from these cells increased endothelial
      cell proliferation. CONCLUSION: These studies reveal that NO derived from NO
      donors or generated by NOS within the cells, upregulates the synthesis of VEGF in
      vascular smooth muscle cells. Administration of NO donors, or augmentation of
      endogenous NO synthesis, may be an alternative approach in therapeutic
      angiogenesis.

PMID- 11530112
TI  - Differential regulation of thrombospondin-1 and fibronectin by angiotensin II
      receptor subtypes in cultured endothelial cells.
AB  - OBJECTIVES: Angiotensin II (ANG II) can modulate cellular proliferation in
      various cell types via AT(1) and AT(2) receptors. In the present study, we
      investigated the effect of the angiotensin AT(1) and AT(2) receptors on DNA
      synthesis as well as on the expression of the extracellular matrix (ECM)
      components, thrombospondin-1 (TSP-1) and fibronectin (FN) in endothelial cells
      (EC). METHODS: The experiments were performed in microvascular EC derived from
      rat heart (CEC) and macrovascular EC derived from bovine aorta (BAEC). The
      experiments were performed in cells of the second and third passage and the
      expression of AT(1) and AT(2) receptors was verified by binding studies, Northern
      analysis or RT-PCR. Quiescent rat CEC and BAEC were stimulated to proliferate by
      the addition of 25 ng/ml bFGF, while ANG II (10(-7) M) and the selective ANG II
      receptor antagonists, Losartan (10(-5) M) and PD123177 (10(-6) M) or the AT(2)
      agonist, CGP42112A (10(-7) M) were added 16 h later. RESULTS: ANG II induced a
      dose-dependent decrease of DNA-synthesis in BAEC measured by [3H]-thymidine
      incorporation. This inhibitory effect of ANG II was prevented by the addition of
      the AT(2) receptor antagonist PD123177 (10(-6) M), demonstrating, that the
      inhibition of DNA synthesis is mediated by the AT(2) receptor. In the presence of
      Losartan, stimulation of both, CEC and BAEC, with ANG II resulted in a marked
      increase of TSP-1 mRNA levels, which was maximal between 3 and 6 h in rat CEC and
      after 9 h in BAEC. In addition, TSP-1 was clearly induced by the AT(2) agonist
      CGP42112A. In contrast, blockade of the AT(2) receptor by the selective AT(2)
      antagonist, PD123177 (10(-6) M), resulted in a pronounced down regulation of FN
      mRNA 9 h after the stimulation. CONCLUSIONS: The present results suggest that the
      ANG II receptor subtype AT(2) mediates growth inhibition in macrovascular EC
      similar to what has been shown before in microvascular rat EC and that AT(2)
      receptors mediates remodeling of the endothelial ECM by upregulation of TSP-1
      expression in both macro- and micro-vascular endothelial cells.

PMID- 11530113
TI  - Professional liability--some solutions.

PMID- 11530114
TI  - Individualized risk assessment for adverse pregnancy outcome by uterine artery
      Doppler at 23 weeks.
AB  - OBJECTIVE: To provide individualized risk prediction of severe adverse pregnancy
      outcome based on uterine artery Doppler screening at 23 weeks. METHODS: Color
      Doppler assessment of the uterine arteries was carried out in 5121 women
      attending for routine care at 23 weeks in two inner-city obstetric units. The
      mean uterine artery pulsatility index (PI) was calculated, and the likelihood
      ratios in relation to PI were generated for severe adverse outcome. This was
      defined as fetal death, placental abruption, and delivery before 34 weeks
      associated with preeclampsia and birth weight less than the 10th centile.
      RESULTS: The likelihood of severe adverse pregnancy outcome increased
      quadratically with mean uterine artery PI. This relationship was not affected by
      maternal age, ethnicity, or parity. At a mean PI of 1.45, the 95th centile for
      our population, the likelihood ratio for severe adverse pregnancy outcome was 5.
      Cigarette smoking had an additional contribution to PI in predicting severe
      adverse outcome, roughly doubling the risk for a given PI. CONCLUSION: The
      individualized risk of severe adverse pregnancy outcome can be determined by
      uterine artery Doppler screening at 23 weeks and knowledge of cigarette smoking
      history. Such individualized risk would allow ultrasound resources and clinical
      follow-up to be tailored to the pregnant woman for the most appropriate use of
      antenatal care.

PMID- 11530115
TI  - Fetal sex determination from maternal plasma in pregnancies at risk for
      congenital adrenal hyperplasia.
AB  - OBJECTIVE: To determine first-trimester fetal sex by isolating free fetal DNA
      from maternal plasma. METHODS: The index case was a pregnant woman who previously
      delivered a girl with congenital adrenal hyperplasia. The SRY gene as a marker
      for the fetal Y chromosome was detected in maternal serum and plasma by
      quantitative polymerase chain reaction analysis. Simultaneously, we performed the
      same test in 25 and 19 women in the first and second trimester, respectively, and
      compared plasma results with fetal gender as assessed by prenatal karyotyping or
      as seen at ultrasound or birth. RESULTS: In 44 of 45 patients at gestational ages
      ranging from 8 3/7 to 17 3/7 weeks, we correctly predicted fetal sex using
      quantitative polymerase chain reaction analysis of the SRY gene in maternal
      plasma. In one case, the test result was inconclusive. Overall, fetal sex was
      correctly predicted in 97.8% of cases (95% confidence interval 88.2%, 99.9%).
      CONCLUSION: Amplification of free fetal DNA in maternal plasma is a valid
      technique for predicting fetal sex in early pregnancy. In case of pregnancies at
      risk for congenital adrenal hyperplasia, the technique allows restriction of
      dexamethasone treatment to female fetuses resulting in a substantial decrease of
      unnecessary treatment and invasive diagnostic tests.

PMID- 11530116
TI  - Recurrence of preterm birth in singleton and twin pregnancies.
AB  - OBJECTIVE: To assess recurrence of preterm birth and its impact on an obstetric
      population. METHODS: Women with consecutive births at our hospital beginning with
      their first pregnancy were identified (n = 15,945). The first pregnancy was
      categorized as delivered between 24 and 34 weeks' gestation or 35 weeks or
      beyond, singleton or twin, and spontaneous or induced. The risk of preterm
      delivery in these same women during subsequent pregnancies was then analyzed.
      RESULTS: Compared with women who delivered a singleton at or beyond 35 weeks'
      gestation in their first pregnancy, those who delivered a singleton before 35
      weeks were at a significant increased risk for recurrence (odds ratio [OR] 5.6,
      95% confidence interval [CI] 4.5, 7.0), whereas those who delivered twins were
      not (OR 1.9, 95% CI 0.46, 8.14). The OR for recurrent spontaneous preterm birth
      presenting with intact membranes was 7.9 (95% CI 5.6, 11.3) compared with 5.5
      (95% CI 3.2, 9.4) with ruptured membranes. Of those women with a recurrent
      preterm birth, 49% delivered within 1 week of the gestational age of their first
      delivery and 70% delivered within 2 weeks. Among 15,863 nulliparous women with
      singleton births at their first delivery, a history of preterm birth in that
      pregnancy could predict only 10% of the preterm births that ultimately occurred
      in the entire obstetric population. CONCLUSION: In a population-based study at
      our hospital, women who initially delivered preterm and thus were identified to
      be at risk for recurrence ultimately accounted for only 10% of the prematurity
      problem in the cohort.

PMID- 11530117
TI  - Comparison of two oxytocin regimens to prevent uterine atony at cesarean
      delivery: a randomized controlled trial.
AB  - OBJECTIVE: To determine if high-dose oxytocin reduces the need for additional
      uterotonic agents at cesarean. METHODS: A randomized, double-masked trial of two
      oxytocin regimens was performed to prevent postpartum uterine atony in laboring
      women. The pharmacy prepared sequentially numbered oxytocin solutions containing
      either 10 U/500 mL or 80 U/500 mL of lactated Ringer's solution infused over 30
      minutes after cord clamping. The need for additional uterotonic agents was
      determined by the surgical team. Hypotension was diagnosed and treated with
      crystalloid or a pressor agent. To detect a 50% decrease in the need for
      additional uterotonic agents and considering a beta error of 0.2, 220 patients
      would be required in each group (alpha = 0.05, two-tailed chi(2) test). RESULTS:
      The low-dose group (n = 163) received 333 mU/min, and the high-dose group (n =
      158) received 2667 mU/min of oxytocin. The groups were similar with respect to
      risk factors for atony. Women in the low-dose group received additional
      uterotonic medication significantly more often than those in the high-dose group
      (39% compared with 19%, P <.001, relative risk 2.1, 95% confidence interval 1.4,
      3.0). Moreover, more women in the low-dose group received methylergonovine, 15
      methyl prostaglandin F(2alpha) or both (9% compared with 2%, relative risk 4.8,
      95% confidence interval 1.4, 16) after additional oxytocin (median 20 U) had been
      added to the study solution. The incidence of hypotension was similar in both
      groups. CONCLUSION: Compared with an infusion rate of 333 mU/min, oxytocin
      infused at 2667 mU/min for the first 30 minutes postpartum reduces the need for
      additional uterotonic agents at cesarean delivery.

PMID- 11530118
TI  - Sleep quality, estradiol levels, and behavioral factors in late reproductive age
      women.
AB  - OBJECTIVE: To estimate the prevalence of perceived poor sleep in women aged 35-49
      years and to correlate sleep quality with levels of gonadal steroids and
      predictors of poor sleep. METHODS: A cohort of 218 black and 218 white women aged
      35-47 years at enrollment (aged 37-49 at final follow-up) with regular menstrual
      cycles was identified through random digit dialing for a longitudinal study of
      ovarian aging correlates. Data obtained at four assessment periods, including
      enrollment, over a 2-year interval were collected between days 1 and 6 (mean =
      3.9) of the menstrual cycle. The primary outcome measure was subjects' rating of
      sleep quality at each assessment period. Associations of sleep quality with
      hormone levels (estradiol, follicle-stimulating hormone, luteinizing hormone,
      testosterone, and dehydroepiandrosterone sulfate) and other clinical, behavioral,
      and demographic variables were examined in bivariable and multivariable analyses.
      RESULTS: Approximately 17% of subjects reported poor sleep at each assessment
      period. Significant independent associations with poor sleep included greater
      incidence of hot flashes (odds ratio [OR] 1.52; 95% confidence interval [CI]
      1.08, 2.12, P =.02), higher anxiety levels (OR 1.03; 95% CI 1.00, 1.06, P =.04),
      higher depression levels (OR 1.05; 95% CI 1.02, 1.07, P <.001), greater caffeine
      consumption (OR 1.25; 95% CI 1.04, 1.49, P =.02), and lower estradiol levels in
      women aged 45-49 (OR 0.53; 95% CI 0.34, 0.84, P =.006), after adjustment for
      current use of sleep medications. CONCLUSION: Both hormonal and behavioral
      factors were associated with sleep quality. Estradiol levels are an important
      factor in poor sleep reported by women in the 45-49 age group. Further evaluation
      of estrogen treatment for poor sleep of women 45 years and older is warranted.

PMID- 11530119
TI  - Annual direct cost of urinary incontinence.
AB  - OBJECTIVE: To estimate the annual direct cost of urinary incontinence in 1995 US
      dollars. METHODS: Epidemiologically based models using diagnostic and treatment
      algorithms from published clinical practice guidelines and current disease
      prevalence data were used to estimate direct costs of urinary incontinence.
      Prevalence and event probability estimates were obtained from literature sources,
      national data sets, small surveys, and expert opinion. Average national Medicare
      reimbursement was used to estimate costs, which were determined separately by
      gender, age group, and type of incontinence. Sensitivity analyses were performed
      on all variables. RESULTS: The annual direct cost of urinary incontinence in the
      United States (in 1995 dollars) was estimated as $16.3 billion, including $12.4
      billion (76%) for women and $3.8 billion (24%) for men. Costs for community
      dwelling women ($8.6 billion, 69% of costs for women) were greater than for
      institutionalized women ($3.8 billion, 31%). Costs for women over 65 years of age
      were more than twice the costs for those under 65 years ($7.6 and $3.6 billion,
      respectively). The largest cost category was routine care (70% of costs for
      women), followed by nursing home admissions (14%), treatment (9%), complications
      (6%), and diagnosis and evaluations (1%). Costs were most sensitive to changes in
      incontinence prevalence, routine care costs, and institutionalization rates and
      costs. CONCLUSION: Urinary incontinence is a very costly condition, with annual
      expenditures similar to other chronic diseases in women.

PMID- 11530120
TI  - Pain perception in women with dysmenorrhea.
AB  - OBJECTIVE: To determine if systemic processing of pain differs in women with and
      without dysmenorrhea. METHODS: Twenty-two dysmenorrheic women and 31
      nondysmenorrheic women were studied by pain threshold and supra-threshold
      magnitude estimation to heat stimuli, pain-evoked potentials by laser stimuli,
      and anxiety scores four times across their menstrual cycles. RESULTS: Significant
      differences were found between dysmenorrheic and nondysmenorrheic women. In all
      four examinations across the menstrual cycle, dysmenorrheic women had longer
      latencies of pain-evoked potentials (383.08 +/- 6.8 msec versus 345.05 +/- 7.0
      msec, P <.001), higher magnitude estimations on visual analog scale of supra
      threshold pain (83.29 +/- 2.87 versus 63.50 +/- 3.82, P <.001), and higher state
      anxiety scores (37.69 +/- 1.7 versus 29.20 +/- 1.9, P =.002). CONCLUSION: Women
      with dysmenorrhea show enhanced pain perception compared to nondysmenorrheic
      women. This augmentation of pain perception may be part of the development of
      dysmenorrhea.

PMID- 11530121
TI  - Development of a bench station objective structured assessment of technical
      skills.
AB  - OBJECTIVE: We have previously shown that objective structured assessment of
      technical skills performed in an animal model was an innovative, reliable, and
      valid method of assessing surgical skills. Our goal was to develop a less costly
      bench station objective structured assessment of technical skills and to evaluate
      the feasibility, reliability, and validity of this exam. METHODS: A seven-station
      examination was administered to 24 residents. The tests included laparoscopic
      procedures (salpingostomy, intracorporeal knot tying, closure of port sites) and
      open abdominal procedures (subcuticular closure, bladder neck suspension, repair
      of enterotomy, abdominal wall closure). All tasks were performed using life-like
      surgical models. Residents were timed and assessed at each station using three
      methods of scoring: a task-specific checklist, a global rating scale, and a
      pass/fail grade. RESULTS: Assessment of construct validity, the ability of the
      test to discriminate among residency levels, found significant differences on the
      checklist, global rating scale, time for procedures, and pass/fail grade by level
      of training. Reliability indices calculated with Cronbach's alpha were 0.77 for
      the checklists and 0.94 for the global rating scale. Overall interrater
      reliability indices were 0.91 for the global rating scale and 0.92 for the
      checklists. Total cost for replaceable parts and facilities was $1900.
      CONCLUSION: The less costly and more portable bench station objective structured
      assessment of technical skills can reliably and validly assess the surgical
      skills of gynecology residents. This type of examination can be a useful tool to
      identify residents who need additional surgical instruction, provide remediation,
      and may become a mechanism to certify surgical skill competence.

PMID- 11530122
TI  - Effect of interferon alpha-2b on endometrioma cells in vitro.
AB  - OBJECTIVE: To examine the effect of interferon alpha-2b on the growth of
      endometrioma cells and its effect on the DNA synthesis. METHODS: Cells from four
      separate endometrioma cell lines were seeded into six-well plates in M199 medium
      containing increasing levels of interferon alpha-2b: 0 (control), 50, 100, 500,
      1000, and 2000 U/mL. All cells were counted on days 0, 3, 6, and 9 in
      quadruplicate, and the counts were averaged for each condition. A second
      experiment was run to demonstrate the effect of short-term exposure of interferon
      alpha-2b on the growth of endometrioma cells in culture. In a separate
      experiment, cells from two endometriomas were plated in quadruplicate to evaluate
      the DNA synthesis. On day 3, 1000 and 4000 U/mL of interferon alpha-2b were added
      and run simultaneously with control (0 U/mL) wells. 3H-thymidine was added to
      each condition for 24 and 48 hours' incubation. Cells were then harvested and
      counted in a scintillation counter to study the 3H-thymidine uptake. RESULTS:
      Interferon alpha-2b suppressed endometrioma cell growth in vitro. This effect
      increased with increasing concentrations of interferon alpha-2b (50-2000 U/mL)
      compared with the control (0 U/mL). The suppression of cell growth was
      statistically significant, but when interferon alpha-2b was removed from the
      culture cell growth increased. 3H-thymidine uptake by endometrioma cells
      decreased compared with the control after 24 and 48 hours for interferon alpha-2b
      concentrations of 1000 and 4000 U/mL, respectively. CONCLUSION: Interferon alpha
      2b inhibits the growth and DNA synthesis of endometrioma cells in culture. This
      finding may have prospects for the treatment of endometriosis.

PMID- 11530124
TI  - Treatment of hypertension in pregnancy: effect of atenolol on maternal disease,
      preterm delivery, and fetal growth.
AB  - OBJECTIVE: To assess the impact of antihypertensive therapy initiated early in
      pregnancy on maternal and fetal outcomes. METHODS: A retrospective review of
      patients treated in early pregnancy with atenolol was conducted. Therapy was
      directed by measurements of cardiac output. Fetal growth was analyzed with
      reference to prior pregnancy outcome, treatment inconsistent with standards
      present at the end of the study period, and year of treatment. Data were analyzed
      by paired and unpaired t-test, analysis of variance for multiple comparisons, and
      linear regression. RESULTS: Two hundred thirty-five pregnancies at risk for
      preeclampsia were studied. Ten percent (n = 22) received additional therapy with
      furosemide; 20% (n = 48) with hydralazine. Six and one half percent had treatment
      inconsistencies. Fifty-five percent had greater than 100 mg of proteinuria at
      baseline. One patient developed severe preeclampsia. Only 2.1% delivered before
      32 weeks; 4.7% delivered before 34 weeks. Low percentile birth weight was
      strongly associated with a prior pregnancy with intrauterine growth restriction
      (P = 0.001), treatment inconsistency (P <.001), and a pregnancy earlier in our
      treatment experience (P <.001). Percentile birth weight increased from the 20th
      at the beginning of the study period to the 40th by the end (P = 0.002).
      CONCLUSION: Early intervention with antihypertensive therapy was associated with
      a low rate of severe maternal hypertension and preterm delivery. The failure to
      adjust therapy in response to an excessive fall in cardiac output or increase in
      vascular resistance was associated with reduced fetal growth.

PMID- 11530123
TI  - Vaginal birth after cesarean in California.
AB  - OBJECTIVE: To estimate rates at which women were offered and consented to trial
      of labor in California hospitals with high and low risk-adjusted cesarean
      delivery rates. METHODS: From 267 nonfederal acute-care hospitals in California
      that performed more than 678 deliveries in 1992-1993, 51 hospitals were selected
      in a stratified sample. Hospitals in the sample were categorized as having high,
      medium, and low risk-adjusted cesarean rates using a logistic regression model
      based on data from the California Patient Discharge Data System. We reviewed
      medical records of women with previous cesareans for evidence of counseling
      regarding trial of labor, other clinical variables, and method of delivery.
      Differences in proportions between the three groups of hospitals were compared.
      RESULTS: According to records of 369 women with previous cesareans, after
      excluding contraindications, 312 were potentially eligible for trial of labor.
      Hospitals with low risk-adjusted cesarean rates documented counseling women for
      trial of labor in over 99% of records reviewed, compared with 85% and 79%,
      respectively, of hospitals with intermediate and high rates (P <.001). Rates of
      completed vaginal births after cesarean were 71% in hospitals with low risk
      adjusted cesarean rates, compared with 39% and 31% in hospitals with intermediate
      and high rates (P <.05). CONCLUSIONS: California hospitals with high cesarean
      rates in 1992-1993 had markedly higher rates of repeat elective cesarean delivery
      without evidence of counseling regarding trial of labor. Informed patient choice
      is a critical element of the decision for trial of labor or elective repeat
      cesarean, and lack of documented counseling is cause for concern.

PMID- 11530125
TI  - Mifepristone 100 mg in abortion regimens.
AB  - OBJECTIVE: To examine the clinical efficacy of mifepristone 100 mg followed 2
      days later by misoprostol 400 microg orally or 800 microg vaginally in women at
      up to 49 days' gestation. METHODS: Eighty participants received mifepristone 100
      mg and then were randomized to misoprostol, administered 48 hours later, at a
      dose of 400 microg orally (group 1) or 800 microg vaginally (group 2). Women
      returned for follow-up evaluations 24 +/- 1 hour after using the misoprostol and
      then 2-3 weeks later. If abortion still had not occurred and the pregnancy was
      nonviable, the subject returned again after an additional 3 weeks. RESULTS:
      Twenty-four hours after receiving misoprostol, 34 (85%; 95% confidence interval
      [CI] 71%, 94%) of the 40 women in group 1 and 38 (95%; 95% CI 85%, 99%) of the 40
      women in group 2 had complete abortions. Overall, complete abortion without
      surgical intervention occurred in 34 women in group 1 (85%; 95% CI 71%, 94%) and
      40 women in group 2 (100%; 95% CI 91%, 100%; P =.03). Four women in group 1
      required suction aspiration for continuing pregnancy at the second follow-up,
      compared with none in group 2 (P =.12). Side effects occurred with similar
      frequency in both treatment groups. CONCLUSION: Low-dose mifepristone (100 mg)
      combined with vaginal misoprostol 800 microg may be an effective alternative to
      regimens using 200 or 600 mg of mifepristone with misoprostol.

PMID- 11530126
TI  - Cervical cancer screening by simple visual inspection after acetic acid.
AB  - OBJECTIVE: To estimate the sensitivity and specificity of visual inspection using
      acetic acid as a primary screen for cervical intraepithelial neoplasia (CIN).
      METHODS: Visual inspection was done on 1997 women aged 35-45 years in a screening
      trial in rural China. Each women had colposcopy and at least five cervical
      biopsies (directed biopsy of lesions, one biopsy at 2, 4, 8, or 10 o'clock at the
      squamocolumnar junction in each normal quadrant, and an endocervical curettage).
      RESULTS: Forty-three women had biopsy-proven CIN II, 31 had CIN III, and 12 had
      invasive cancer. In two women only the endocervix was positive (one with CIN II
      and one with CIN III). Visual inspection yielded normal results in 1445 women
      (72%), low-grade intraepithelial neoplasia in 525 (26%), high-grade in 21 (1%),
      and cancer in six (0.3%). With abnormal visual inspection defined as low-grade
      intraepithelial neoplasia or worse, the sensitivity for detecting biopsy proven
      CIN II or worse was 71% (61 of 86, 95% confidence interval [CI] 60%, 80%); the
      specificity was 74% (1420 of 1911, 95% CI 72%, 76%); the sensitivity was 65% for
      smaller lesions (37 of 57, 95% CI 51%, 77%), and 89% for larger lesions (24 of
      27, 95% CI 71%, 98%) (P =.03). CONCLUSION: The sensitivity of visual inspection
      equaled or exceeded reported rates for conventional cervical cytology. Visual
      inspection and colposcopy have similar specificity profiles for CIN II and
      greater. The benefit of an inexpensive point-of-care diagnosis and treatment
      algorithm will be a powerful incentive to pursue visual inspection for cervical
      cancer screening in developing countries.

PMID- 11530127
TI  - Relationship of androgens to muscle size and bone mineral density in women with
      polycystic ovary syndrome.
AB  - OBJECTIVE: To investigate the relationship of androgens to regional muscle size
      and bone mineral density (BMD) in women with polycystic ovary syndrome (PCOS).
      METHODS: Seventy-one amenorrheic and right-side dominant women with PCOS (mean
      age +/- standard deviation 28.1 +/- 6.7 years) were enrolled. Baseline
      characteristics included age, height, weight, and body mass index (BMI). Regional
      BMD and lean mass were measured by whole-body scanning with dual-energy x-ray
      absorptiometry. Serum levels of testosterone, dehydroepiandrosterone sulfate
      (DHEAS), and androstenedione were measured by radioimmunoassay. Correlations
      between regional BMD and variables were investigated using a Pearson correlation
      test and multiple regression analysis. RESULTS: Serum testosterone levels
      correlated significantly with lean mass of the left arm, right arm, trunk, left
      leg, and right leg (r =.34, P <.05 to r =.50, P <.01). Regional lean mass
      correlated significantly with respective regional BMD (r =.30, P <.05 to r =.68,
      P <.001). These relationships remained significant after adjusting for age,
      height, and weight. Serum testosterone levels were not correlated with BMD of the
      bilateral arms and lumbar spine. Although serum testosterone levels correlated
      with leg BMD (r =.34, P <.05 to r =.45, P <.01), significance did not persist
      after adjusting for respective regional lean mass. CONCLUSION: Testosterone
      influences regional BMD through increasing regional muscle mass in women with
      polycystic ovary syndrome.

PMID- 11530128
TI  - Influence of postmenopausal hormone replacement therapy on platelet serotonin
      uptake site and serotonin 2A receptor binding.
AB  - OBJECTIVE: To examine whether binding of [3H]paroxetine to the platelet serotonin
      transporter or binding of [3H]lysergic acid diethylamide (LSD) to the platelet 5
      HT(2A) receptor are influenced by postmenopausal estrogen/progestogen treatment.
      METHODS: Twenty-three postmenopausal women with climacteric symptoms completed
      this double-blind, randomized, crossover study. The women received 2 mg of
      estradiol continuously during four 28-day cycles. In the last 14 days of each
      cycle, 10 mg of medroxyprogesterone acetate, 1 mg of norethindrone acetate, or
      placebo was given. Before treatment, as well as once during the last week of each
      treatment, blood samples were collected for analysis of [3H]LSD and
      [3H]paroxetine binding. The power of the study setup was 81%. The study had an
      effect size of 0.36, corresponding to the ability to detect a 15% difference in
      [3H]paroxetine and [3H]LSD binding between treatments with alpha =.05 and beta
      =.20, based on a previously reported standard deviation within cells of 20% of
      the mean binding values. RESULTS: The number of platelet receptors (B(max)), or
      the affinity of the radioligand to the receptor (K(d)), for [3H]paroxetine
      binding did not change during estrogen or estrogen-progestogen treatment, nor did
      B(max) or K(d) for [3H]LSD binding change during the different treatments.
      However, in a subgroup of depressed patients, the decrease in B(max) for [3H]LSD
      binding during treatment was significantly more pronounced than in the
      nondepressed subgroup (P <.05). CONCLUSION: Estrogen treatment with or without
      the addition of progestogen does not affect binding to the serotonin transporter
      or to the serotonergic 5-HT(2A) receptor in healthy postmenopausal women.

PMID- 11530129
TI  - Placental and serum levels of carotenoids in preeclampsia.
AB  - OBJECTIVE: We compared placental tissue, maternal serum, and umbilical cord
      venous blood levels of four dietary carotenoids (alpha-carotene, beta-carotene,
      lycopene, and canthaxanthin) in normal pregnant women and those with
      preeclampsia. METHODS: Levels of alpha-carotene, beta-carotene, lycopene, and
      canthaxanthin were measured in placental tissue, maternal serum, and umbilical
      cord venous blood from 22 normal pregnant women and 19 women with preeclampsia.
      The criteria for recruitment included gestational age of 30-42 weeks, singleton
      pregnancy, intact membranes, absence of labor contractions, and absence of any
      other medical complication concurrent with preeclampsia. Carotenoids were
      measured using high-pressure liquid chromatography. RESULTS: All four carotenoids
      were detectable in human placental tissue, maternal serum, and umbilical cord
      venous blood samples. The levels of beta-carotene, lycopene, and canthaxanthin in
      placentas from preeclamptic women were significantly lower (P =.032, .009, and
      .013, respectively, by Mann-Whitney test) than those from normal pregnant women.
      Maternal serum levels of beta-carotene and lycopene were significantly lower (P
      =.004 and .008, respectively, by Mann-Whitney test) in women with preeclampsia.
      However, umbilical cord venous blood levels of these carotenoids were not
      significantly different between the two groups. CONCLUSION: Lower placental
      tissue and maternal serum carotenoid levels in women with preeclampsia suggest
      that oxidative stress or a dietary antioxidant influence might have an effect on
      the pathophysiology of preeclampsia.

PMID- 11530130
TI  - Bioactivity of serum hCG in preeclampsia.
AB  - OBJECTIVE: To compare hCG levels, obtained by biologic and immunologic means, in
      women with normal pregnancies and women with preeclampsia. METHODS: Peripheral
      blood samples from women in the third trimester with preeclampsia (n = 30) or
      normal pregnancies (n = 30) were assayed for immunoactive and bioactive hCG
      (mouse Leydig cell testosterone production assay). RESULTS: Serum bioactive hCG
      levels tended to be lower than normal, and immunoactive hCG levels tended to be
      higher in women with preeclampsia, but the differences were not statistically
      significant. However, the ratio of bioactive to immunoactive hCG was
      significantly lower than normal for preeclamptic women (0.70 +/- 0.28 vs. 1.15 +/
      0.35 for normotensive pregnant women [mean +/- standard deviation], P <.001).
      CONCLUSION: The ratio of bioactive to immunoreactive serum hCG is lower among
      preeclamptic than among normotensive pregnant women.

PMID- 11530131
TI  - Fetal monkey surfactants after intra-amniotic or maternal administration of
      betamethasone and thyroid hormone.
AB  - OBJECTIVE: To compare direct intra-amniotic injection of betamethasone and
      thyroxine (T4) with maternal treatment and controls for accelerating pulmonary
      surfactant production. METHODS: Twelve pregnant monkeys (Macaca mulatta) on
      gestational day 125 (term 165 +/- 10 days) had surfactant protein A and B
      concentrations measured in amniotic fluid. In four controls, normal saline was
      injected into the amniotic fluid; four others (intra-amniotic) received intra
      amniotic betamethasone (1 mg) and T4 (60 microg); and in four others (maternal),
      the dam was given betamethasone (12 mg) intramuscularly, repeated in 24 hours,
      plus TRH (400 microg) intravenously, repeated every 6 hours for 24 hours. Seventy
      two hours after the initial amniocentesis, a hysterotomy was performed and fetal
      tissue and amniotic fluid harvested for determination of surfactant protein A and
      B concentrations and immunohistochemical staining for surfactant protein A.
      RESULTS: Amniotic fluid surfactant protein A was higher with intra-amniotic
      injection than with maternal treatment (P <.04) or controls (P =.07). Amniotic
      fluid surfactant protein B was higher in the intra-amniotic group than in
      controls (P =.06). Immunohistochemical staining for surfactant protein A in the
      lung tissue was increased in the intra-amniotic group compared with controls
      (0.145 +/- 0.01 versus 0.097 +/- 0.001, percent positive staining for surfactant
      protein A cells per lung tissue cells; P <.03). Birth weight was greater in the
      intra-amniotic group compared with the maternal group (P <.03) although not
      different from the controls. Finally, gut motility and the presence of formed
      meconium were increased in the intra-amniotic group compared with the other
      groups (P <.05). CONCLUSION: Intra-amniotic injection of betamethasone and T4
      enhanced lung (and possibly intestinal) maturation of the preterm rhesus fetal
      monkey compared with maternal injections.

PMID- 11530132
TI  - Venous thromboembolism in pregnant Chinese women.
AB  - OBJECTIVE: To evaluate the incidence, disease pattern, and risk factors for
      thromboembolism in pregnant Chinese women. METHODS: We conducted a study from
      January 1998 to December 2000. Women with thromboembolic diseases were identified
      and their case records retrieved and reviewed. Demographic characteristics were
      compared between women with and without thromboembolism. RESULTS: Thirty-two
      women were diagnosed as having thromboembolic disease during the study period.
      The total number of deliveries over the study period was 16,993, giving an
      incidence of 1.88 per 1000 deliveries. There were two cases of pulmonary embolism
      and one resulted in a maternal death. The others had deep vein thrombosis of
      which over 80% were limited to calf veins only. The ultrasound examinations
      requested for suspected deep venous thrombosis before and after the event of
      maternal death were 1.62 and 10.7 per 1000 deliveries (P <.001); and the
      corresponding cases of deep venous thrombosis diagnosed were 0.29 and 2.94 per
      1000 deliveries, respectively (P <.001). The majority (75%) of cases were
      diagnosed in the postpartum period, mainly after cesarean delivery. Women with
      venous thromboembolism were older, had higher body mass index, and a higher
      incidence of preeclampsia. CONCLUSION: Thromboembolic disease is not uncommon
      among pregnant Chinese women. The incidence was similar to that of the white
      population, although the sites of vascular occlusion were different. The long
      standing belief that thromboembolism is rare among Chinese is at least partly
      because of underdiagnosis.

PMID- 11530133
TI  - Interleukin-10 administration and bacterial endotoxin-induced preterm birth in a
      rat model.
AB  - OBJECTIVE: To determine whether intra-uterine infusion of interleukin-10 prevents
      preterm delivery in rats treated with endotoxin. METHODS: Pregnant rats underwent
      implantation of uterine catheters and were randomly assigned to receive
      intrauterine infusion of either normal saline, 50 microg lipopolysaccharide
      endotoxin, or 50 microg lipopolysaccharide with 500 ng interleukin-10
      administered either concurrently or 24 hours later. The interval from infusion to
      delivery for each group was recorded, along with the number of live born pups and
      their birth weight. We calculated that to obtain a power of 80%, assuming a 24
      hour difference in the treatment to delivery times between the test and control
      subjects, at least six animals would be needed in each group. RESULTS: In females
      receiving lipopolysaccharide (50 microg) alone, the interval to delivery (P
      <.05), live birth rate (P <.05), and pup weight (P <.001) were reduced compared
      with the saline-infused controls. In contrast, females receiving interleukin-10
      at the time of the endotoxin challenge or 24 hours after delivered at term with
      no difference in litter size or live birth weight compared with the controls.
      CONCLUSION: Animals treated with both lipopolysaccharide and interleukin-10,
      administered concurrently or 24 hours after the endotoxin challenge, delivered
      normal weight pups at term with a similar litter size as the saline-infused
      controls. Interleukin-10 appears to be effective in preventing endotoxin-induced
      preterm birth and fetal wastage in pregnant rats.

PMID- 11530134
TI  - The moment of reality.

PMID- 11530135
TI  - Fetal DNA in maternal plasma: emerging clinical applications.
AB  - OBJECTIVE: To review the potential clinical diagnostic applications of fetal DNA
      analysis in maternal plasma or serum for noninvasive prenatal diagnosis and
      screening. DATA SOURCES: We conducted a MEDLINE search of articles published
      between January 1970 and March 2000 using the key terms "fetal DNA," "plasma,"
      and "serum." METHODS OF STUDY SELECTION: All 369 articles describing the
      detection of fetal DNA in maternal plasma were reviewed. RESULTS: The diagnostic
      use of circulating fetal DNA in maternal plasma is currently limited to genes
      that are present in the fetus but not in the mother. From a clinical perspective,
      the most advanced application is for noninvasive detection of fetal rhesus D
      (Rh[D]) genotype. The results of studies performed by four different groups
      showed that prenatal diagnosis of fetal Rh(D) status by molecular analysis of
      maternal plasma or serum is routinely possible beginning in the second trimester.
      Noninvasive fetal genotyping should be useful for the treatment of sensitized
      Rh(D)-negative women whose partners are heterozygous for the Rh(D) gene because
      no further diagnostic or therapeutic procedures are necessary if the fetus is
      Rh(D) negative. Future clinical applications of fetal DNA may be in its use as a
      screening test for Down syndrome, preeclampsia, or preterm labor. However, these
      applications currently rely on the detection of Y chromosomal sequences and
      consequently are limited presently to male fetuses. CONCLUSION: The recent
      discovery of high concentrations of fetal DNA in maternal plasma represents a
      promising noninvasive approach to prenatal diagnosis. Compared with the analysis
      of the cellular fraction of maternal blood, the analysis of fetal DNA extracted
      from maternal plasma has the advantage of being rapid, robust, and easy to
      perform. The fetal DNA detected is limited to the current pregnancy. However,
      universal fetal gene sequences must be identified that allow analysis of genetic
      material from both male and female fetuses. Study of fetal DNA in maternal plasma
      can improve our understanding of fetomaternal biology and physiology. The long
      term effects of maternal exposure to relatively high amounts of foreign DNA are
      unknown but represent an exciting area for future inquiry.

PMID- 11530136
TI  - Multiple courses of antenatal steroids: risks and benefits.
AB  - OBJECTIVE: To review the existing literature regarding the effect of multiple
      courses of antenatal corticosteroids in reducing the occurrence of complications
      arising because of lung immaturity. DATA SOURCES: A systematic review of the
      English-language literature was conducted using a computerized database. We
      searched the English-language human and animal literature in MEDLINE and PubMed
      (National Library of Medicine, Bethesda, MD), as well as abstracts from recent
      meetings of the Society for Gynecologic Investigation and the Society for
      Maternal-Fetal Medicine. The search terms used were antenatal steroids, prenatal
      steroids, and respiratory distress syndrome. STUDY SELECTION: We screened 2472
      abstracts and found 280 relevant articles, which we independently reviewed. Only
      prospective well-designed animal studies were included. In humans, no well
      designed randomized controlled trials (RCTs) were identified. Data that
      specifically addressed the issue of beneficial and adverse outcome of multiple
      courses of antenatal corticosteroids were included. TABULATION, INTEGRATION, AND
      RESULTS: Twelve studies and three abstracts concerning animal models were
      included. These suggest multiple adverse consequences including decrease in birth
      and lung weights and brain growth restriction. In humans, 14 publications and
      five abstracts, mostly in the form of retrospective studies, although
      methodologically lacking, were included. Possible beneficial effects include
      lower rates of respiratory distress syndrome and a decrease in oxygen use,
      whereas adverse outcomes embody reduction in birth head circumference, birth
      weights, and increased neonatal and maternal infection rates. CONCLUSION: To
      date, there are no well-designed RCTs in humans that support the advantages of
      multiple courses over a single course of antenatal corticosteroids. An increasing
      body of evidence raises the concern of adverse consequences from the use of
      repeated courses. While awaiting results from RCTs in progress, we recommend that
      a single course of antenatal corticosteroids be given to all women at risk for
      preterm birth at 24-34 weeks' gestation.

PMID- 11530137
TI  - Hormone replacement therapy and breast cancer: a qualitative review.
AB  - OBJECTIVE: To assess whether recent epidemiologic evidence supports an
      association between use of estrogen replacement therapy or hormone replacement
      therapy and risk of breast cancer. DATA SOURCES: The keywords "estrogen,"
      "estrogen replacement therapy," or "hormone replacement therapy," and "breast
      cancer" or "breast neoplasm," were used to search for articles published from
      1975-2000 in MEDLINE and Dialogweb. Only articles published in peer-reviewed
      journals and containing original data were included in this review. METHODS:
      Unadjusted or age-adjusted risk estimates for breast cancer among ever users of
      estrogen therapy compared with never users were abstracted from published
      articles or calculated using the data provided in the published reports.
      TABULATION, INTEGRATION, AND RESULTS: We found little consistency among studies
      that estimated the risk of breast cancer in hormone users compared with nonusers
      and in studies assessing the risk by duration of use. However, there was
      consistently a lower risk of death from breast cancer in hormone users compared
      with nonusers. CONCLUSION: The evidence did not support the hypotheses that
      estrogen use increases the risk of breast cancer and that combined hormone
      therapy increases the risk more than estrogen only. Additional observational
      studies are unlikely to alter this conclusion. Although a small increase in
      breast cancer risk with hormone therapy or an increased risk with long duration
      of use (15 years or more) cannot be ruled out, the likelihood of this must be
      small, given the large number of studies conducted to date.

PMID- 11530138
TI  - Noninvasive techniques to detect fetal anemia due to red blood cell
      alloimmunization: a systematic review.
AB  - OBJECTIVE: To estimate, in maternal red blood cell alloimmunization, the
      diagnostic value of fetal ultrasonography and Doppler blood flow velocity in the
      evaluation and prediction of fetal anemia. METHODS: Literature from 1970 to 2000
      was identified using general bibliographic databases (MEDLINE and EMBASE), the
      Cochrane Library and relevant specialist register of the Cochrane Collaboration,
      and by checking reference lists of known primary and review articles. Studies
      were selected if the accuracy of the fetal ultrasound parameters or Doppler
      studies of blood flow in the fetal vessels was estimated compared with a
      reference standard (fetal hemoglobin). The diagnostic tests evaluated were
      ultrasound measurement of the fetal spleen perimeter and Doppler studies of blood
      velocity estimates in the umbilical vein, ductus venosus, middle cerebral artery,
      thoracic aorta, and umbilical vessel combined with the thoracic aorta. Study
      selection, quality assessment, and data abstraction were performed independently
      and in duplicate. Data from the selected studies were abstracted as 2 x 2 tables
      comparing the diagnostic test result with the reference standard. Diagnostic
      accuracy was expressed as likelihood ratios. RESULTS: The review included eight
      primary studies with 362 pregnancies affected by red cell alloimmunization.
      Prospective patient recruitment and complete population details were reported in
      half of the selected studies (four of eight). Only one study reported masking the
      diagnostic test results to clinicians. The diagnostic test performance varied
      widely according to the type of the test evaluated and the cutoff level used to
      define fetal anemia, which varied from study to study. The diagnostic test study
      of highest methodological quality reported a positive likelihood ratio of 8.45
      (95% confidence interval 4.69, 15.56) and negative likelihood ratio of 0.02 (95%
      confidence interval 0.001, 0.25) for maximum middle cerebral artery Doppler
      velocity. CONCLUSION: The literature reporting noninvasive techniques to predict
      fetal anemia is methodologically poor and a standard approach to the evaluation
      of these techniques is lacking. A recommendation for practice cannot be generated
      without further rigorous research.

PMID- 11530140
TI  - Protecting patient privacy: striking a balance.

PMID- 11530141
TI  - Mannose-binding lectin in prediction of susceptibility to infection.

PMID- 11530142
TI  - Exacerbations of asthma--still room for improvement.

PMID- 11530143
TI  - Enzyme-replacement therapy for Anderson-Fabry disease.

PMID- 11530144
TI  - Veterinary link to drug resistance in human African trypanosomiasis?

PMID- 11530145
TI  - 100 years' observation of risks from radiation for British (male) radiologists.

PMID- 11530146
TI  - Efficacy and safety of tenecteplase in combination with enoxaparin, abciximab, or
      unfractionated heparin: the ASSENT-3 randomised trial in acute myocardial
      infarction.
AB  - BACKGROUND: Current fibrinolytic therapies fail to achieve optimum reperfusion in
      many patients. Low-molecular-weight heparins and platelet glycoprotein IIb/IIIa
      inhibitors have shown the potential to improve pharmacological reperfusion
      therapy. We did a randomised, open-label trial to compare the efficacy and safety
      of tenecteplase plus enoxaparin or abciximab, with that of tenecteplase plus
      weight-adjusted unfractionated heparin in patients with acute myocardial
      infarction. METHODS: 6095 patients with acute myocardial infarction of less than
      6 h were randomly assigned one of three regimens: full-dose tenecteplase and
      enoxaparin for a maximum of 7 days (enoxaparin group; n=2040), half-dose
      tenecteplase with weight-adjusted low-dose unfractionated heparin and a 12-h
      infusion of abciximab (abciximab group; n=2017), or full-dose tenecteplase with
      weight-adjusted unfractionated heparin for 48 h (unfractionated heparin group;
      n=2038). The primary endpoints were the composites of 30-day mortality, in
      hospital reinfarction, or in-hospital refractory ischaemia (efficacy endpoint),
      and the above endpoint plus in-hospital intracranial haemorrhage or in-hospital
      major bleeding complications (efficacy plus safety endpoint). Analysis was by
      intention to treat. FINDINGS: There were significantly fewer efficacy endpoints
      in the enoxaparin and abciximab groups than in the unfractionated heparin group:
      233/2037 (11.4%) versus 315/2038 (15.4%; relative risk 0.74 [95% CI 0.63-0.87],
      p=0.0002) for enoxaparin, and 223/2017 (11.1%) versus 315/2038 (15.4%; 0.72 [0.61
      0.84], p<0.0001) for abciximab. The same was true for the efficacy plus safety
      endpoint: 280/2037 (13.7%) versus 347/2036 (17.0%; 0.81 [0.70-0.93], p=0.0037)
      for enoxaparin, and 287/2016 (14.2%) versus 347/2036 (17.0%; 0.84 [0.72-0.96],
      p=0.01416) for abciximab. INTERPRETATION: The tenecteplase plus enoxaparin or
      abciximab regimens studied here reduce the frequency of ischaemic complications
      of an acute myocardial infarction. In light of its ease of administration,
      tenecteplase plus enoxaparin seems to be an attractive alternative reperfusion
      regimen that warrants further study.

PMID- 11530147
TI  - Deficiency of mannose-binding lectin and burden of infection in children with
      malignancy: a prospective study.
AB  - BACKGROUND: Infection is a major cause of morbidity and mortality in children
      with malignancy. Individuals with serum deficient in mannose-binding lectin (MBL)
      an important component of the innate immune system-are more susceptible to
      infection than those with adequate concentrations. In this study, we investigated
      the capacity of this protein to influence infectious complications in children
      undergoing treatment for malignancy. METHODS: We enrolled 100 children receiving
      chemotherapy for malignancy at a children's hospital in London, UK. The
      frequency, duration, and causes of febrile neutropenic episodes were recorded,
      and MBL genotype and phenotype were determined by heteroduplex analysis and
      ELISAs, respectively. Serial MBL concentrations were also measured in patients
      during febrile episodes, and the results correlated with the MBL genotype (A/A
      indicating wild type, O/O indicating homozygous for MBL structural-gene
      mutations, and A/O indicating heterozygous for such mutations). FINDINGS: In the
      A/A patients, MBL concentrations almost doubled by day 7 of the febrile
      neutropenic episode before declining by day 14 (p=0.004). By contrast, in
      patients with MBL mutations, concentrations did not alter significantly during
      the neutropenic episode. In the 6 months after initial diagnosis, most patients
      had at least one febrile neutropenic episode, but the median duration in patients
      with MBL mutations was twice as long as that in children with the wildtype
      genotype (20.5 days vs 10.0 days; p=0.014). Individuals with the lowest serum MBL
      concentrations at the time of diagnosis (<1000 microg/L) had a higher median
      number of days of febrile neutropenia than did individuals with higher
      concentrations of MBL (p=0.012). INTERPRETATION: MBL deficiency seems to have an
      important influence on the duration of febrile neutropenic episodes in children
      with malignancy. This finding suggests that MBL infusions could represent a new
      therapeutic approach which would aid the management of chemotherapy-induced
      complications in this population of children.

PMID- 11530148
TI  - Indoor air pollution from biomass combustion and acute respiratory infections in
      Kenya: an exposure-response study.
AB  - BACKGROUND: Acute respiratory infections (ARI) are the leading cause of the
      global burden of disease and have been causally linked with exposure to
      pollutants from domestic biomass fuels in less-developed countries. We used
      longitudinal health data coupled with detailed monitoring of personal exposure
      from more than 2 years of field measurements in rural Kenya to estimate the
      exposure-response relation for particulates smaller than 10 mm in diameter
      (PM(10)) generated from biomass combustion. METHODS: 55 randomly-selected
      households (including 93 infants and children, 229 individuals between 5 and 49
      years of age, and 23 aged 50 or older) in central Kenya were followed up for more
      than 2 years. Longitudinal data on ARI and acute lower respiratory infections
      (ALRI) were recorded at weekly clinical examinations. Exposure to PM(10) was
      monitored by measurement of PM(10) emission concentration and time-activity
      budgets. FINDINGS: With the best estimate of the exposure-response relation, we
      found that ARI and ALRI are increasing concave functions of average daily
      exposure to PM(10), with the rate of increase declining for exposures above about
      1000-2000 mg/m(3). After we had included high-intensity exposure episodes, sex
      was no longer a significant predictor of ARI and ALRI. INTERPRETATION: The
      benefits of reduced exposure to PM(10) are larger for average exposure less than
      about 1000-2000 mg/m(3). Our findings have important consequences for
      international public-health policies, energy and combustion research, and
      technology transfer efforts that affect more than 2 billion people worldwide.

PMID- 11530149
TI  - The origins of a new Trypanosoma brucei rhodesiense sleeping sickness outbreak in
      eastern Uganda.
AB  - BACKGROUND: Sleeping sickness, caused by two trypanosome subspecies, Trypanosoma
      brucei gambiense and Trypanosoma brucei rhodesiense, is a parasitic disease
      transmitted by the tsetse fly in sub-Saharan Africa. We report on a recent
      outbreak of T b rhodesiense sleeping sickness outside the established south-east
      Ugandan focus, in Soroti District where the disease had previously been absent.
      Soroti District has been the subject of large-scale livestock restocking
      activities and, because domestic cattle are important reservoirs of T b
      rhodesiense, we investigated the role of cattle in the origins of the outbreak.
      METHODS: We identified the origins of cattle entering the outbreak area in the 4
      years preceding the outbreak. A matched case-control study was conducted to
      assess whether the distance of villages from the main market involved with
      restocking was a risk factor for sleeping sickness. We investigated the spatial
      clustering of sleeping sickness cases at the start of the outbreak. FINDINGS:
      Over 50% (1510 of 2796) of cattle traded at the market were reported to have
      originated from endemic sleeping sickness areas. The case-control study revealed
      that distance to the cattle market was a highly significant risk factor for
      sleeping sickness (p<0.001) and that there was a significant clustering of cases
      (27 of 28) close to the market at the start of the outbreak (p<0.001). As the
      outbreak progressed, the average distance of cases moved away from the cattle
      market (0.014 km per day, 95% CI 0.008-0.020 km per day, p<0.001).
      INTERPRETATIONS: The results are consistent with the disease being introduced by
      cattle infected with T b rhodesiense imported to the market from the endemic
      sleeping sickness focus. The subsequent spread of the disease away from the
      market suggests that sleeping sickness is becoming established in this new focus.
      Public health measures directed at controlling the infection in the animal
      reservoir should be considered to prevent the spread of sleeping sickness.

PMID- 11530150
TI  - Asthma severity and adequacy of management in accident and emergency departments
      in France: a prospective study.
AB  - BACKGROUND: Recent guidelines have enabled doctors to establish accident and
      emergency department management strategies for acute asthma on the basis of
      severity of exacerbations at presentation. However, there is no available
      information on acute asthma patients classified according to severity of disease.
      Our aim was to describe the severity of such exacerbations at presentation, and
      the adequacy of treatment and management. METHODS: We did a 12-month multicentre
      cross-sectional observational cohort study in adult patients with acute asthma
      who attended one of 37 accident and emergency departments in France. The doctors
      who examined the patients obtained information using a formatted chart. We
      classified exacerbations according to severity (life-threatening, severe, or mild
      to moderate), on the basis of clinical findings and peak expiratory flow value,
      as defined by currently used guidelines. FINDINGS: Of 3772 patients with acute
      asthma, 975 (26%) had life-threatening attacks, 1834 (49%) had severe
      exacerbations without life-threatening features, and 963 (26%) had mild to
      moderate exacerbations. Initial treatment included nebulised b2 agonists,
      anticholinergics, and systemic corticosteroids in 3492 (93%), 1841 (49%), and
      2252 (60%), respectively. According to severity classification, anticholinergics
      were used in 494 (51%), 913 (50%), and 434 (45%) of patients in life-threatening,
      severe, and mild to moderate exacerbations groups, respectively; corticosteroids
      were given in 666 (68%), 1117 (61%), and 468 (49%), respectively. The overall
      admission rate was 54.2%, and mean stay was 6.1 (SD 6.0) days. Patients were
      admitted in 747 (77%), 1018 (55%), and 278 (29%) of cases in life-threatening,
      severe, and mild to moderate groups, respectively. Three patients died in
      hospital. INTERPRETATION: Acute asthma exacerbations are often life-threatening
      in patients who attend accident and emergency departments, and management of
      patients is not ideal, mainly because of underuse of corticosteroids and
      inappropriate admission rates according to severity.

PMID- 11530152
TI  - A swollen finger and abdominal pain.

PMID- 11530153
TI  - Association between deficiency of mannose-binding lectin and severe infections
      after chemotherapy.
AB  - The plasma protein mannose-binding lectin (MBL) activates the complement system
      by binding to carbohydrate structures presented by microorganisms and thus could
      be an important component of the innate immune defence system. We measured MBL in
      patients with leukaemia who were scheduled to undergo chemotherapy (ie, a
      population especially susceptible to infection) and related the results to
      severity of infection after chemotherapy. We showed a significant association
      between low concentrations of MBL and serious infections related to chemotherapy
      (p<0.0001). These results suggest that increasing concentrations of MBL in
      patients having chemotherapy could reduce susceptibility to infection.

PMID- 11530154
TI  - Multislice spiral computed tomography angiography of mesenteric arteries.
AB  - The introduction of multislice technology has improved and expanded the clinical
      applications of computed tomography angiography (CTA), and it is now possible to
      detect subtle vascular abnormalities. We optimised a high resolution CTA protocol
      to study the anatomy of mesenteric arteries with a multislice spiral CT scanner.
      We showed that multislice CTA produces images of high quality, with excellent
      anatomical visualisation of the main mesenteric trunks, and small collateral
      vessels. CTA may facilitate the diagnosis of vascular diseases, such as chronic
      mesenteric ischaemia, as well as acute disorders such as gastrointestinal
      bleeding.

PMID- 11530155
TI  - Effect on neonatal tetanus mortality after a culturally-based health promotion
      programme.
AB  - The Maasai have high rates of death from neonatal tetanus, partly due to their
      custom of packing the umbilical stump with cow dung. We report on the effect of a
      simple health promotion programme, designed in consultation with the local
      community and carried out by local women. After introduction of the programme in
      1981, neonatal (<6 weeks of age) tetanus rates fell sharply, and by 1988 annual
      death rates had dropped to 0.75 (range 0-3) per 1000 births in the intervention
      areas compared with 82 (74-93) per 1000 in control areas.

PMID- 11530156
TI  - Exposure to ultraviolet radiation: association with susceptibility and age at
      presentation with prostate cancer.
AB  - A positive association between latitude and prostate cancer mortality has been
      interpreted to indicate that ultraviolet radiation (UVR) protects against
      development of this cancer. We aimed to examine this hypothesis. We compared
      exposure between 210 cases and 155 controls. Childhood sunburn (odds ratio 0.18,
      95% CI 0.08-0.38), regular foreign holidays(0.41, 0.25-0.68), sunbathing score
      (0.83, 0.76-0.89), and low exposure to UVR (3.03, 1.59-5.78) were associated with
      development of prostate cancer. Furthermore, cases with low UVR exposure
      developed cancer at a younger median age (67.7 years, IQR 61.5-74.6) than cases
      with higher exposure (72.1 years, 67.5-76.4); p=0.006. These findings are
      compatible with UVR having a protective role against prostate cancer.

PMID- 11530157
TI  - Call for decriminalisation of prostitution in Asia.

PMID- 11530158
TI  - Ageing brains put both hemispheres to work on complex tasks.

PMID- 11530162
TI  - Untangling the relation between beta-amyloid and tau.

PMID- 11530163
TI  - Researchers suggest relaxation of food guidelines before colon cancer test.

PMID- 11530164
TI  - 1966 and all that-when is a literature search done?

PMID- 11530165
TI  - Japan starts on health-spending slowdown.

PMID- 11530166
TI  - Spain launches database of biomedical researchers.

PMID- 11530167
TI  - Canadian drive to curb drug expenditure.

PMID- 11530169
TI  - Most Ugandan HIV-positive mothers insist on breastfeeding.

PMID- 11530172
TI  - The road ahead for the European Food Authority.

PMID- 11530173
TI  - Recurrent renal stone disease-advances in pathogenesis and clinical management.
AB  - Kidney stones are common in industrialised nations: up to 15% of white men and 6%
      of all women will develop one stone, with recurrence in about half these people.
      Risk factors for formation of stones include urinary promoters (calcium, urate,
      cystine, and sodium) and urinary inhibitors (magnesium, citrate, and
      nephrocalcin). Acute renal colic can be precipitated by dehydration and reduced
      urine output, increased protein intake, heavy physical exercise, and various
      medicines. Such colic manifests as severe loin pain and can be accompanied by
      frequent urination, dysuria, oliguria, and haematuria. Documentation of stone
      characteristics is extremely important: type, size, location, and underlying
      metabolic abnormalities. Such details can be obtained with a combination of
      biochemical investigations, microscopic examination of urine under polarised
      light, and an intravenous pyelogram. Ultrasonography and plain abdominal
      radiographs are also useful, especially for patients unable to tolerate an
      intravenous pyelogram. Acute therapy includes complete pain relief, rehydration,
      and encouragement of diuresis. Long-term management encompasses education of
      patients with regard to diet and fluid intake, control of calciuria, citrate
      replacement, and treatment of any underlying urinary-tract infection or metabolic
      abnormality. Stones smaller than 5 mm normally pass spontaneously, whereas larger
      stones, as big as 2 cm, are best treated with extracorporeal shock-wave
      lithotripsy. All physicians should have a clear understanding of the pathogenesis
      and clinical management (acute treatment and prevention of recurrence) of renal
      stone disease.

PMID- 11530174
TI  - Estimated risk of HIV transmission by blood transfusion in Kenya.
AB  - BACKGROUND: During the past decade, developing countries have received limited
      support for blood safety programmes. The Kenya Ministry of Health did a
      collaborative multicentre assessment to establish the risk of HIV transmission by
      transfusion in Kenya, to promote awareness of blood safety issues in this country
      with a mature HIV epidemic, and to identify methods to reduce the risk of HIV
      transmission by blood transfusion in Kenya. METHODS: For 12 weeks, from April to
      July 1994, we collected information and blood samples from all blood donors, and
      pretransfusion samples were collected from all recipients in six government
      hospitals in Kenya. Blood donations were collected and screened for HIV according
      to standard practice in the hospital laboratories. Test results at a reference
      laboratory were compared with those of the hospital laboratories and risk of
      transfusion-associated HIV transmission was calculated. FINDINGS: The prevalence
      of HIV among blood donors was 6.4% (120 of 1877) and varied by hospital (range 2
      20%). HIV test results were available for 1290 donor-recipient pairs. Of these,
      26 HIV-positive donations were given to HIV-negative patients. We estimate that
      2.0% of transfusions transmitted HIV. Problems in the hospitals that contributed
      to transfusion risk included inconsistent refrigeration, data entry errors,
      equipment failure, and lack of a quality-assurance programme. INTERPRETATION: A
      high proportion of blood transfusions transmitted HIV in this high-prevalence
      area of Africa, primarily because of erroneous laboratory practices. On the basis
      of these results, the Kenya Ministry of Health introduced a number of practical
      and inexpensive interventions to improve national blood safety.

PMID- 11530175
TI  - Global cardiovascular disease prevention: time to get serious.

PMID- 11530181
TI  - A bottle of beer.

PMID- 11530183
TI  - Novel cell culture systems for the hepatitis C virus.
AB  - Infections with the hepatitis C virus (HCV) are a major cause of acute and
      chronic liver disease. The high prevalence of the virus, the insidious course of
      the disease and the poor prognosis for long-term persistent infection make this
      pathogen a serious medical and socioeconomical problem. The identification of the
      viral genome approximately 10 years ago rapidly led to the delineation of the
      genomic organization and the structural and biochemical characterization of
      several virus proteins. However, studies of the viral life cycle as well as the
      development of antiviral drugs have been difficult because of the lack of a
      robust and reliable cell culture system. Numerous attempts have been undertaken
      in the past few years but only recently a highly efficient cell culture model
      could be developed. This system is based on the self replication of engineered
      HCV minigenomes (replicons) in a transfected human hepatoma cell line. A summary
      of the various HCV cell culture models with a focus on the replicon system and
      its use for drug development is described.

PMID- 11530184
TI  - Lack of effect of treatment with penciclovir or acyclovir on the establishment of
      latent HSV-1 in primary sensory neurons in culture.
AB  - Recent studies suggest reductions in establishment of herpes simplex virus, type
      1 (HSV-1) latency using the nucleoside analog penciclovir compared with acyclovir
      in the murine model. These observations raise the possibility that the new
      analogs may have novel activities that directly interfere with the establishment
      of the latent infection, suggesting a mechanism other than simply blocking the
      productive infection. To determine if penciclovir has a direct action on the
      establishment of latency, we compared the effects of penciclovir versus acyclovir
      in an in vitro model of HSV-1 latency in rat dorsal root ganglia neurons in
      culture. In neurons in culture, both penciclovir and acyclovir were highly
      effective in blocking the productive infection. However, neither penciclovir nor
      acyclovir blocked establishment of latency as demonstrated by similar percentages
      of neurons expressing the latency-associated transcript (LAT). Following removal
      of the respective nucleoside analog, latency was maintained until reactivation
      was induced by nerve growth factor deprivation. Similar virus titers were
      recovered after induction of reactivation of latent infections, which were
      established in the presence of either penciclovir or acyclovir. These results
      indicate that neither penciclovir nor acyclovir treatment directly prevents the
      establishment of latent HSV-1 infections in primary sensory neurons in culture.

PMID- 11530185
TI  - Preclinical evaluation of docusate as protective agent from herpes simplex
      viruses.
AB  - Prevention of sexually transmitted infections (STIs) is key to public health
      efforts to control these diseases. An effective vaginal microbicide could provide
      topical, broad-spectrum prevention against the transmission of several STI
      pathogens. Docusate is a sulfated surfactant and, as such, may inactivate viral
      pathogens by disrupting viral envelopes and/or denaturing/disassociating
      proteins. Accordingly, the in vitro efficacy and toxicity of docusate (dioctyl
      sodium sulfosuccinate; Zorex; Meditech Pharmaceuticals, Inc., Scottsdale,
      Arizona) against herpes simplex viruses (HSV) were evaluated. Docusate was
      effective in vitro against wild type and drug-resistant strains of HSV type 1 and
      2 with EC(90-100) (effective concentration giving 90-100% virus yield reduction)
      of approximately 0.005% (w/v). Sodium dodecyl sulfate (SDS) was equipotent,
      however, docusate was somewhat less toxic to uninfected Vero cells compared with
      SDS after 2 days incubation (docusate CC(50) approximately 0.01% vs. SDS
      approximately 0.005%). The cytotoxicity profiles of docusate were time- and dose
      dependent and thus associated with the frequency of use. Kinetics of inactivation
      examined by pre-mixing virus and drug in a time-course experiment demonstrated
      that docusate could reach its EC(90-100) within 30 min. Docusate pretreatment of
      cells was associated with a 45% reduction in infectivity of those cells, despite
      a triple washing procedure. Once infected, an approximate 30% plaque reduction
      was observed with treatment.

PMID- 11530186
TI  - Virus inactivation and protein modifications by ethyleneimines.
AB  - Virus inactivation by ethyleneimines was first introduced more than 30 years ago.
      Selective targeting of nucleic acids was reported for oligomeric ethyleneimines.
      In this study, trimeric ethyleneimine (TEI) was used to inactivate minute virus
      of mice (MVM; Parvoviridae) and Semliki forest virus (SFV; Togaviridae). The pH
      dependency of the inactivation kinetics observed with MVM was different compared
      to the kinetics reported for other viruses. The higher inactivation rate at
      higher pH favoured the idea of a mechanism involving protein modifications.
      Alteration of the isoelectric point and changes in mass could be observed after
      treatment of soluble proteins with TEI. The uptake of MVM by host cells was
      reduced or completely blocked by TEI treatment, as shown by monitoring viral
      internalisation of DNA into target cells. The observed loss of virus infectivity
      coincided with the inhibition of virus uptake. Thus, virus inactivation by TEI is
      most likely also a result of chemical modifications of viral surface proteins.

PMID- 11530187
TI  - Serum amyloid P component inhibits influenza A virus infections: in vitro and in
      vivo studies.
AB  - Serum amyloid P component (SAP) binds in vitro Ca(2+)-dependently to several
      ligands including oligosaccharides with terminal mannose and galactose. We have
      earlier reported that SAP binds to human influenza A virus strains, inhibiting
      hemagglutinin (HA) activity and virus infectivity in vitro. These studies were
      extended to comprise five mouse-adapted influenza A strains, two swine influenza
      A strains, a mink influenza A virus, a ferret influenza A reassortant virus, a
      influenza B virus and a parainfluenza 3 virus. The HA activity of all these
      viruses was inhibited by SAP. Western blotting showed that SAP bound to HA
      trimers, monomers and HA1 and HA2 subunits of influenza A virus. Binding studies
      indicated that galactose, mannose and fucose moieties contributed to the SAP
      reacting site(s). Intranasal administration of human SAP to mice induced no
      demonstrable toxic reactions, and circulating antibodies against SAP were not
      detected. Preincubation of virus (A/Japan/57) with SAP prevented primary
      infection of mice and development of antiviral antibodies. After a single
      intranasal administration of SAP (40 microg) 1 h before primary infection with
      virus (2LD(50)), nine out of 10 mice survived on day 10 and these mice approached
      normal body weight, whereas control mice (one out of five surviving on day 10)
      died. The data provide evidence of the potential of intranasally administered SAP
      for prophylactic treatment of influenza A virus infections in humans.

PMID- 11530188
TI  - Effects of cidofovir on the pathogenesis of a lethal vaccinia virus respiratory
      infection in mice.
AB  - Intranasal infection of BALB/c mice with the WR strain of vaccinia virus leads to
      pneumonia, profound weight loss, and death. Although the major sites of virus
      replication are in the lungs and nasal tissue, dissemination of the virus to
      other visceral organs and brain occurs via the blood. In this report the effects
      of cidofovir on the pathogenesis of the infection was studied. Mice were infected
      intranasally with virus followed 1 day later by a single intraperitoneal
      treatment with cidofovir (100 mg/kg) or placebo. Placebo-treated mice were dead
      by day 8, whereas all cidofovir-treated animals survived through 21 days.
      Cidofovir treatment did not prevent profound weight loss from occurring during
      the acute phase of the infection, but the mice gained weight quickly after the
      8th day. Significantly higher arterial oxygen saturation levels, as determined by
      pulse oximetry, were seen in cidofovir-treated animals compared to placebos on
      days 4-7. Cidofovir treatment markedly improved lung consolidation scores and
      prevented lung weights from increasing during the infection. Virus titers in
      lungs and nasal tissue were high starting from the first day of the infection,
      whereas the titers in liver, spleen, brain, and blood was low for 3 days then
      markedly rose between days 4 and 6. Lung and nasal virus titers were reduced 10
      30-fold by cidofovir treatment on days 2, 4 and 6. Virus titers in the other
      tissues and blood at their peak (day 6) were 30- to >1000-fold less than in
      tissues of placebos. These results illustrate the ability of a single cidofovir
      treatment to control the pathogenesis of an acute lethal infection in various
      tissues during the vaccinia virus infection in mice.

PMID- 11530191
TI  - Targeted screening of high-risk cattle populations for BSE to augment mandatory
      reporting of clinical suspects.
AB  - In Switzerland, the first case of bovine spongiform encephalopathy (BSE) was
      diagnosed in November 1990. Case numbers peaked in 1995, with a total of 352 BSE
      cases identified by 30 April 2000. Reporting of clinically suspect cattle is
      currently the most commonly used method world-wide to detect BSE cases. The
      effectiveness of mandatory reporting depends on a variety of factors; for other
      diseases passive surveillance underestimates the incidence of clinical cases. The
      efficiency of passive surveillance systems for BSE will remain unknown until
      screening tests able to identify clinically affected cattle have been applied in
      several countries. This paper provides the first detailed description of a
      targeted screening programme for BSE. Two populations of cows >24 months of age
      were included in the targeted screening: (i) cows found dead or culled on site
      where the carcass was submitted to rendering (fallen stock) and (ii) cows with
      health-related problems unfit for routine slaughter that were slaughtered under
      emergency procedures (emergency slaughter). Between 1992 and 1999, on average 81
      clinical BSE suspects per year were reported to the veterinary authorities
      (passive surveillance), of which 43% were confirmed with BSE. A total of 30
      clinical cases were captured by passive surveillance and an additional 20 BSE
      cases detected by targeted screening between May 1999 and April 2000. The odds of
      finding a BSE case was 49 times higher in the fallen stock and 58 times higher in
      emergency-slaughtered cattle when compared to passive surveillance. The targeted
      screening of fallen stock and emergency-slaughtered cattle considerably increased
      the number of detected cases in this 12-month period. Targeted-screening cases
      were on average 4 months younger than the clinical suspect cases. In conclusion,
      post-mortem testing of fallen stock and emergency-slaughtered cows >24 months for
      BSE is an important active surveillance element within a total surveillance
      system that principally is based on mandatory reporting of clinical suspect
      cases. Without ante-mortem screening tests to detect BSE-infected cattle during
      the incubation period, a combination of effectively functioning passive and
      active BSE surveillance strategies might be the only approach to assess the BSE
      situation reliably in a given country or region - and it is necessary to
      substantiate claims of freedom from the disease.

PMID- 11530189
TI  - Peptide T inhibits HIV-1 infection mediated by the chemokine receptor-5 (CCR5).
AB  - Peptide T, which is derived from the V2 region of HIV-1, inhibits replication of
      R5 and dual-tropic (R5/X4) HIV-1 strains in monocyte-derived macrophages (MDMs),
      microglia, and primary CD4(+)T cells. Little to no inhibition by peptide T was
      observed with lab adapted X4 viruses such as IIIB, MN, or NL4-3 propagated in
      CD4(+) T cells or in the MAGI entry assay. The more clinically relevant R5/X4
      early passage patient isolates were inhibited via either the X4 or R5 chemokine
      receptors, although inhibition was greater with R5 compared to X4 receptors.
      Virus inhibition ranged from 60 to 99%, depending on the assay, receptor target,
      viral isolate and amount of added virus. Peak inhibitory effects were detected at
      concentrations from 10(-12) to 10(-9) M. Peptide T acted to block viral entry as
      it inhibited in the MAGI cell assay and blocked infection in the luciferase
      reporter assay using HIV virions pseudotyped with ADA envelope. These results
      using early passage virus grown in primary cells, together with two different
      entry reporter assays, show that peptide T selectively inhibits HIV replication
      using chemokine receptor CCR5 compared to CXC4, explaining past inconsistencies
      of in vitro antiviral effects.

PMID- 11530192
TI  - Time to first calving and calving interval in bovine virus diarrhoea virus (BVDV)
      sero-converted dairy herds in Norway.
AB  - Dairy herds in More and Romsdal County, Norway (regarded as initially free from
      the bovine virus diarrhoea virus (BVDV) infection) were studied retrospectively
      from 1992 to 1996. The herd reproductive performance (time to first calving,
      calving interval, and number of breeding services) was investigated for a
      potential effect of BVDV sero-conversion. The herd culling pattern--possibly
      affecting the above measurements--was included for investigation. Two different
      statistical models were used: the generalised estimating equation (GEE) method
      and multilevel modelling using Gibbs sampling. Though slightly different
      estimates resulted, both models agreed on an effect of BVDV in the second year
      after sero-conversion on the herd average time to first calving by--on an average
      - 14-16 days. In subsets of case herds testing positive for BVDV antibodies among
      young stock, the impact on time to first calving tended to be more pronounced by
      an additional increase of 18 days. No effect on the number of breeding services
      for heifers or cows was observed (indicating a need to search for other
      determinants than reduced conception risk). There appeared to be no effect of
      BVDV on the herd average calving interval. There was a tendency for a higher risk
      for reporting animals lost/died in sero-converted herds, which we believe might
      be related to the occurrence of mucosal disease.

PMID- 11530193
TI  - Activities to address antimicrobial resistance in the United States.
AB  - Antimicrobials are essential for the prevention and treatment of bacterial
      infections in humans and animals. Subtherapeutic antimicrobials have been used as
      growth promoters for >40 years. The subject of antimicrobial resistance is not
      new but has gained increasing attention due to public-health concerns about multi
      resistant pathogenic organisms. Numerous United States' activities do exist to
      address antimicrobial resistance. A surveillance system (the National
      Antimicrobial Resistance Monitoring System) was established in 1996 to monitor
      changes over time in resistance for 17 antibiotics in humans and animals.
      Educational campaigns have been created to promote the judicious therapeutic use
      of antimicrobials. Producer groups are developing guidelines for judicious
      therapeutic antimicrobial use for their prospective species. Basic and applied
      research programs are being expanded to answer many of the unsolved questions
      regarding development, persistence, and transmission of antimicrobial resistance.
      This paper focuses on a federal inter-agency public-health action plan to combat
      antimicrobial resistance; the plan was released for public comment in 2000. This
      plan addresses goals and actions to combat antimicrobial resistance in humans and
      agriculture in four areas: surveillance; research; prevention and control;
      product development.

PMID- 11530194
TI  - A survival analysis of trypanosomosis diagnostic-test performance under natural
      infection challenge.
AB  - Little is known about the time-to-first detection and the time difference (TD)
      between first parasitological and first serological diagnosis of Trypanosoma spp.
      infections under natural infection challenge in cattle. The objective of our
      study was to estimate these measures of "longitudinal aspects" of diagnostic
      performance and to investigate potential biological factors. Emphasis was on
      diagnosis at the genus level (Trypanosoma spp.). Twelve N'Dama, 12 Gobra zebu and
      12N'DamaxGobra (F1) crossbred cattle (all animals non-infected at the start of
      the experiment, six male and six female animals in each cohort) were exposed to
      natural high tsetse challenge in the Niamina East area in The Gambia [Acta Trop.
      71 (1998) 57]. The animals were investigated parasitologically (detection of
      trypanosomes by buffy-coat technique), serologically (detection of T. brucei, T.
      congolense and T. vivax antigen by enzyme-linked immunosorbent assay (ELISA)) and
      clinically (packed-cell volume, PCV) over a period of 180 days. The time-to-first
      detection of trypanosomes, trypanosomal antigen (cut-off as suggested by test
      supplier) and drop in PCV (subject-based cut-off values) were recorded as
      outcomes of interest. Thus, incidence was both parasitologically (I(p)),
      serologically (I(s)) and clinically (I(c)). Recurrent events were not considered.
      The TD between first parasitological and first serological detection was
      established as I(s) time minus I(p) time. The effect of breed and sex on the time
      to-first detection and on TD was investigated using Cox (proportional hazard)
      regression and ANOVA, respectively. We found that time-to-first parasitological
      detection of trypanosomosis in N'Dama animals was significantly longer than in
      the two other breeds (Cox regression, P=0.002). A similar but less-strong
      (P=0.063) effect of breed on time-to-first detection of trypanosomal antigen was
      found, whereas no breed effect was observed for clinical detection (P=0.432). Sex
      had no effect in all detection systems. The TD varied between -56 and 115 (mean
      28). Marked differences among breeds and between sexes were not observed (ANOVA,
      P=0.8). We suggest that incidence studies are more suitable for detecting risk
      factors for animal trypanosomosis than prevalence-based (cross-sectional) studies
      because the latter often result in misinterpretation of factors that increase the
      survival time with infection as risk factors.

PMID- 11530195
TI  - Farm-management and milking practices associated with the presence of Listeria
      monocytogenes in New York state dairy herds.
AB  - Knowledge of the relationship between dairy herd management and milking practices
      with the occurrence of Listeria monocytogenes on dairy farms might assist in the
      development of intervention strategies aimed at eliminating this organism at the
      pre-harvest dairy-food-production level. This paper represents a first step
      towards that goal. We carried out a cross-sectional study to identify farm
      factors that were associated with isolation of L. monocytogenes from on-farm in
      line milk-filters. Data on these factors were collected by personal interview of
      the farm owners or managers. Logistic regression was used to evaluate the
      significance of association of each factor while simultaneously controlling for
      the presence of other factors. A systematic approach was developed in which the
      bivariable association of the hypothesized factors initially was evaluated. All
      significant factors were then jointly evaluated in a multivariable logistic
      model. Farms that used a bucket system had significantly higher odds of L.
      monocytogenes as compared to farms that used a round-the-barn pipeline milking
      system (OR=0.35,P=0.05) or milking parlor (OR=0.21,P=0.01). There was a
      significant association between pre-milking teat disinfection (OR=0.26,P=0.001)
      and pre-milking examination of abnormal appearance of milk (OR=0.4,P=0.01)
      against the occurrence of L. monocytogenes. We also found a significant
      association between the use of E. coli J5 vaccine (OR=3.3,P=0.03) and how long
      dry-cow therapy had been used on farm (OR=0.34,P=0.04).

PMID- 11530196
TI  - An economic model to calculate farm-specific losses due to bovine respiratory
      disease in dairy heifers.
AB  - This paper describes a personal-computer-based model estimating the economic
      losses associated with clinical bovine respiratory disease in replacement heifers
      raised on individual dairy farms. The model is based on the partial-budgeting
      technique, and calculates the losses for two types of the disease separately:
      calf pneumonia and a seasonal outbreak. Model input includes farm-specific data
      such as the incidence of bovine respiratory disease, prices, and effects of the
      disease on the heifers' productivity. The input database was linked directly with
      the economic model. For all input parameters, default values used are available
      to the user and can be modified easily. Losses considered by the model include
      treatment expenditures and costs associated with increased mortality, increased
      premature culling, reduced growth, reduced fertility and reduced milk production
      in first lactation. Uncertainty is taken into account for parameters related to
      disease incidence, mortality and culling.Basic calculations for a typical Dutch
      dairy farm with 60% of the heifers (<3 months) affected, indicated total annual
      losses due to pneumonia average 31.2 per heifer present on the farm (range 18.4
      57.1). The estimated losses for one seasonal outbreak with heifers up to 15
      months old affected were 27.0 per heifer present (range 17.2-43.1). For both BRD
      types, the model's outcome was most sensitive to the number of heifers affected.
      Most of the parameters that had a major impact on the total losses were related
      to treatment or to the effects on the heifers' productivity. The model is user
      friendly and flexible, and can be used as an interactive tool by farmers and
      veterinarians in the (economic) decision-making process regarding on-farm
      prevention and control of bovine respiratory disease.

PMID- 11530197
TI  - Cost-efficient vaccination of foxes (Vulpes vulpes) against rabies and the need
      for a new baiting strategy.
AB  - In this study, ecological models, optimisation algorithms and threshold analysis
      were linked to develop oral-vaccination strategies against rabies in fox
      populations. It is important that such strategies are cost-efficient and
      resistant to environmental conditions which would lessen their success. The model
      validation shows that the ecological models used are suited to predict the
      proportion of tetracycline- (TC) marked foxes in the course of time. This figure
      indicates the proportion of foxes which had at least one contact to vaccine
      baits, and is based on the design of the vaccination strategy (i.e. the number
      and timing of vaccination campaigns and the number of baits used per square
      kilometre and campaign). The design of a vaccination strategy also determines the
      costs. It is the combination of ecological models and optimisation algorithms
      that helped us to design a vaccination strategy which is capable of achieving a
      continuous rate of >70% of TC-marked foxes within an analytical horizon of 3
      years at low costs. Compared to the standard strategy (baseline comparator), the
      improved strategy incurs just over half of the cost while almost doubling the
      number of weeks during which the proportion of TC-marked foxes is >70%. In the
      improved strategy, June is recommended as the time for bait distribution. The
      standard strategy, however, avoids summer months (because high temperatures
      reduce the durability of the baits) which again leads to a reduction of the bait
      intake by the foxes. Using threshold analysis, we examined the effect of a
      reduced durability of the baits on the design of the improved vaccination
      strategy. We concluded that distribution of baits in June was optimal given that
      the durability of baits is above a threshold of 7 days.

PMID- 11530198
TI  - The generation and persistence of genetic variation in foot-and-mouth disease
      virus.
AB  - Genetic variation in foot-and-mouth disease virus (FMDV) is of interest for at
      least two reasons. First, changes to the genes encoding capsid proteins results
      in antigenic variation, and affects vaccine efficiency and effectiveness of
      vaccination programs; second, genetic changes can lead to important insights into
      the transport of virus between countries, regions, herds, and even possibly
      individuals. Current estimates of RNA virus mutation rates suggest that an
      average of about one base mis-incorporation is likely to occur each time a single
      FMDV genome replicates. This should result in the introduction of every possible
      1-step mutation from the progenitor genotype into the viraemia of a single
      infected animal many times a day. In the absence of purifying selection, a single
      infected animal should therefore generate a genetically very diverse population
      of virus.Viral-capsid sequences obtained from infected animals sampled over long
      term FMDV epidemics suggest that these genetic changes accrue in a remarkably
      linear 'clock-like' fashion and at rates of around 1% change per year. While such
      a rate is generally regarded as quite high, it is actually somewhat lower than
      one might expect based on the rate at which viral diversity could be generated
      within a single animal. The difference might be explained in a variety of
      possible ways: (1) the mutation rate has been overestimated; (2) purifying
      selection is stronger than predicted; (3) only a restricted subset of excreted
      virus is actually infectious; (4) infected animals only excrete virus from a
      small partitioned subset of amplified virus, and that most of the generated viral
      diversity is unable to exit the animal; or (5) only a small fraction of all
      infected animals participate in the actual disease-transmission process.

PMID- 11530200
TI  - Abstracts of the 2nd International Chicago Symposium on Malignancies of the
      Chest, Head and Neck. Chicago, Illinois, USA. October 4-6, 2001.

PMID- 11530199
TI  - An epidemiological analysis of a canine-biopsies database compiled by a
      diagnostic histopathology service.
AB  - A case-control study was carried out on data from 21,371 canine tissue biopsies
      submitted to the external histopathology diagnostic service at the University of
      Glasgow Veterinary School (GUVS) over a 12.5-year period. Biopsies were received
      from 545 privately owned and charity veterinary practices located throughout the
      UK. The overall prevalence of neoplasia in samples with a confirmed diagnosis was
      58.7%. A total of 156 pure breeds were represented in the dataset, with 22.2% of
      samples originating from mixed-breed dogs. Univariable and multivariable analyses
      assessed the effects of sex, breed, age and site on the likelihood of a diagnosis
      of neoplasia. Logistic regression showed that the highest odds ratio was
      associated with the mammary gland (OR=6.53;skin=the referent category). Using the
      Labrador retriever as the referent breed, Boxers had increased odds of neoplasia;
      the German shepherd dog and Doberman were among breeds with decreased odds
      ratios. Intact females and dogs over the age of 10 years were (unsurprisingly)
      also high-risk groups. Potential sources of bias influencing the dataset include
      the relative ease with which clinical abnormalities of the skin and mammary gland
      initially are detected by sight and/or palpation, compared with other organs. The
      high prevalence of biopsies originating from the skin and mammary gland is also
      likely to reflect the readiness of the veterinarian to biopsy lesions in these
      sites, compared with sites within the body cavities. The findings confirm many of
      the perceived risks for neoplasia based on previous clinical descriptive and
      univariable investigations. The results might also assist the pathologist in
      prioritisation of biopsy examination in busy histopathology laboratories.

PMID- 11530201
TI  - Genetic model organisms in the study of N-glycans.
AB  - Recently the genomic sequences of three multicellular eukaryotes, Caenorhabditis
      elegans, Drosophila melanogaster and Arabidopsis thaliana, have been elucidated.
      A number of cDNAs encoding glycosyltransferases demonstrated to have a role in N
      linked glycosylation have already been cloned from these organisms, e.g., GlcNAc
      transferases and alpha 1,3-fucosyltransferases. However, many more homologues of
      glycosyltransferases and other glycan modifying enzymes have been predicted by
      analysis of the genome sequences, but the predictions of full length open reading
      frames appear to be particularly poor in Caenorhabditis. The use of these
      organisms as models in glycobiology may be hampered since they all have N-linked
      glycosylation repertoires unlike those of mammals. Arabidopsis and Drosophila
      have glycosylation similar to that of other plants or insects, while our new data
      from MALDI-TOF analysis of PNGase A-released neutral N-glycans of Caenorhabditis
      indicate that there exists a range of pauci- and oligomannosidic structures, with
      up to four fucose residues and up to two O-methyl groups. With all these three
      'genetic model organisms', however, much more work is required for a full
      understanding of their glycobiology.

PMID- 11530202
TI  - Structural and functional features of glycosyltransferases.
AB  - Most of the glycosylation reactions that generate the great diversity of
      oligosaccharide structures of eukaryotic cells occur in the Golgi apparatus. This
      review deals with the most recent data that provide insight into the functional
      organization of Golgi-resident glycosyltransferases. We also focus on the recent
      successes in X-ray crystal structure determination of glycosyltransferases. These
      new structures begin to shed light on the molecular bases accounting for donor
      and acceptor substrate specificities as well as catalysis.

PMID- 11530204
TI  - The human sialyltransferase family.
AB  - The human genome encodes probably more than 20 different sialyltransferases
      involved in the biosynthesis of sialylated glycoproteins and glycolipids but to
      date only 15 different human sialyltransferase cDNAs have been cloned and
      characterized. Each of the sialyltransferase genes is differentially expressed in
      a tissue-, cell type-, and stage-specific manner to regulate the sialylation
      pattern of cells. These enzymes differ in their substrate specificity, tissue
      distribution and various biochemical parameters. However, enzymatic analysis
      conducted in vitro with recombinant enzyme revealed that one linkage can be
      synthesized by multiple enzymes. We present here an overview of these human genes
      and enzymes, the regulation of their occurrence and their involvement in several
      physiological and pathological processes.

PMID- 11530203
TI  - Occurrence of poly-N-acetyllactosamine synthesis in Sf-9 cells upon transfection
      of individual human beta-1,4-galactosyltransferase I, II, III, IV, V and VI
      cDNAs.
AB  - Lectin blot analysis of membrane glycoprotein samples from Sf-9 cells upon
      transfection of individual human beta-1,4-galactosyltransferase (beta-1,4-GalT)
      I, II, III, IV, V et VI cDNAs showed that the endogenous N-linked
      oligosaccharides are galactosylated (Guo et al., Glycobiology (2001), in press).
      Further analysis revealed that membrane glycoprotein samples from all the gene
      transfected cells are also reactive to Lycopersicon esculentum agglutinin (LEA)
      et Datura stramonium agglutinin (DSA), both of which bind to oligosaccharides
      with poly-N-acetyllactosamine chains while no lectin reactive protein bands are
      detected when blots are pretreated with a mixture of diplococcal beta-1,4
      galactosidase et jack bean beta-N-acetylhexosaminidase or N-glycanase. Analysis
      of endo-beta-galactosidase-digestion products revealed the presence of the Gal1-
      >GlcNAc1-->Gal and/or GlcNAc1-->Gal structures in the gene-transfected cells.
      When the homogenates of the gene-transfected cells were used as enzyme sources
      towards oligosaccharides with the GlcNAc beta 1-->(3Gal beta 1-->4GlcNAc)(1-3)
      structures, human recombinant beta-1,4-GalTs I et II galactosylated these
      oligosaccharides more effectively than other beta-1,4-GalTs. These results
      indicate that beta-1,4-GalTs I-VI can synthesize poly-N-acetyllactosamine chains
      with beta-1,3-N-acetylglucosaminyltransferase.

PMID- 11530205
TI  - Neutrophils promote the release of alpha-6-fucosyltransferase from blood
      platelets through the action of cathepsin G and elastase.
AB  - Human blood platelets release alpha-6-fucosyltransferase during coagulation of
      blood or after stimulation with thrombin or other agonists that cause platelet
      activation (Antoniewicz et al., FEBS Lett. 244 (1989) 388-390). However, in the
      absence of neutrophils the thrombin-stimulated platelets release only a small
      fraction of alpha-6-fucosyltransferase activity (Koscielak et al., Acta Biochim.
      Polon. 42 (1995) 35-40). We show that the effect of neutrophils is reproduced by
      cathepsin G or (less efficiently) by elastase, the two enzymes that are released
      by neutrophils during coagulation of blood. We have also localized alpha-6
      fucosyltransferase to membrane and alpha-granule fractions of platelets that had
      been disrupted by nitrogen cavitation. It is concluded that thrombin-activated
      neutrophils release cathepsin G and elastase that promote degranulation of
      platelets and hence the secretion of alpha-6-fucosyltransferase.

PMID- 11530206
TI  - Activity of fucosyltransferases and altered glycosylation in cystic fibrosis
      airway epithelial cells.
AB  - Cystic fibrosis (CF) glycoconjugates have a glycosylation phenotype of increased
      fucosylation and/or decreased sialylation when compared with non-CF. A major
      increase in fucosyl residues linked alpha 1,3 to antennary GlcNAc was observed
      when surface membrane glycoproteins of CF airway epithelial cells were compared
      to those of non-CF airway cells. Importantly, the increase in the fucosyl
      residues was reversed with transfection of CF cells with wild type CFTR cDNA
      under conditions which brought about a functional correction of the Cl(-) channel
      defect in the CF cells. In contrast, examination of fucosyl residues in alpha 1,2
      linkage by a specific alpha 1,2 fucosidase showed that cell surface glycoproteins
      of the non-CF cells had a higher percentage of fucose in alpha 1,2 linkage than
      the CF cells. Airway epithelial cells in primary culture had a similar reciprocal
      relationship of alpha 1,2- and alpha 1,3-fucosylation when CF and non-CF surface
      membrane glycoconjugates were compared. In striking contrast, the enzyme activity
      and the mRNA of alpha 1,2 fucosyltransferase did not reflect the difference in
      glycoconjugates observed between the CF and non-CF cells. We hypothesize that
      mutated CFTR may cause faulty compartmentalization in the Golgi so that the
      nascent glycoproteins encounter alpha 1,3FucT before either the sialyl- or alpha
      1,2 fucosyltransferases. In subsequent compartments, little or no terminal
      glycosylation can take place since the sialyl- or alpha 1,2 fucosyltransferases
      are unable to utilize a substrate, which is fucosylated in alpha 1,3 position on
      antennary GlcNAc. This hypothesis, if proven correct, could account for the CF
      glycophenotype.

PMID- 11530207
TI  - Influence of culture conditions on the alpha 1,2-fucosyltransferase and MUC gene
      expression of a transformed cell line MM-39 derived from human tracheal gland
      cells.
AB  - Human tracheal glands cells (HTGC) in culture are able to respond to adrenergic,
      cholinergic and purinergic agonists by increasing their serous and mucin
      secretions. These secretagogues are also able to maintain an optimal
      responsiveness of serous cells to stimulation when they are regularly and briefly
      delivered to the cells, making the HTGC a suitable model to study the serous
      secretion (Merten, in press). Our interest has been focused on the effects of
      cholinergic and purinergic secretagogues associated to histamine, on the mucous
      function of the transformed human tracheal gland cell line MM-39, which has a
      mixed, both serous and mucous, phenotype. When the cells were exposed to short
      stimulation every 2 days for 3 weeks with 10 or 100 microM carbachol, UTP and
      histamine, modifications of their mucous phenotype were observed. The expression
      of MUC genes appeared dependent on the culture conditions. Transcripts of MUC1,
      MUC4, and MUC5B genes were observed when the cells were regularly exposed to the
      mixture of secretagogues at a concentration of 10 microM, in contrast to the
      unstimulated expression of MUC1 and MUC4 in control cells. MUC1, MUC4, MUC7, MUC6
      and MUC11 transcripts were observed when the cells were regularly exposed to the
      mixture of secretagogues at a concentration of 100 microM. These culture
      conditions were also able to induce an alpha 1,2-fucosyltransferase activity
      absent in the MM-39 cells cultivated with standard conditions. There was no
      marked effect on the alpha 2,3-sialyltransferase activity although the expression
      pattern of the sialyltransferase genes was reduced to the unique presence of
      ST3Gal III. In conclusion, MM-39 cells exposed to repeated stimulation by
      secretagogues at different concentrations express different sero-mucous
      phenotypes.

PMID- 11530208
TI  - Structure and function of Class I alpha 1,2-mannosidases involved in glycoprotein
      synthesis and endoplasmic reticulum quality control.
AB  - Class I alpha 1,2-mannosidases (glycosylhydrolase family 47) are conserved
      through eukaryotic evolution. This protein family comprises three subgroups
      distinguished by their enzymatic properties. The first subgroup includes yeast
      (Saccharomyces cerevisiae) and human alpha 1,2-mannosidases of the endoplasmic
      reticulum that primarily form Man(8)GlcNAc(2) isomer B from Man(9)GlcNAc(2). The
      second subgroup includes mammalian Golgi alpha 1,2-mannosidases, as well as
      enzymes from insect cells and from filamentous fungi, that trim Man(9)GlcNAc(2)
      to Man(8)GlcNAc(2) isomers A and/or C intermediates toward the formation of
      Man(5)GlcNAc(2). Yeast and mammalian proteins of the third subgroup have no
      enzyme activity with Man(9)GlcNAc(2) as substrate. The members of subgroups 1 and
      3 participate in endoplasmic reticulum quality control and promote proteasomal
      degradation of misfolded glycoproteins. The yeast endoplasmic reticulum alpha 1,2
      mannosidase has served as a model for structure-function studies of this family.
      Its structure was determined by X-ray crystallography as an enzyme-product
      complex. It consists of a novel (alpha alpha)(7) barrel containing the active
      site that includes essential acidic residues and calcium. The structures of the
      subgroup 1 human endoplasmic reticulum alpha 1,2-mannosidase and of a subgroup 2
      fungal alpha 1,2-mannosidase were determined by molecular replacement. Comparison
      of the enzyme structures is providing some insight into the reasons for their
      different specificities.

PMID- 11530209
TI  - Trafficking and localisation of resident Golgi glycosylation enzymes.
AB  - The localisation of glycosylation enzymes within the Golgi apparatus is
      fundamental to the regulation of glycoprotein and glycolipid biosynthesis.
      Regions responsible for specifying Golgi localisation have been identified in
      numerous Golgi resident enzymes. The transmembrane domain of Golgi
      glycosyltransferases provides a dominant localisation signal and in many cases
      there are also major contributions from the lumenal domain. The mechanism by
      which these targeting domains function in maintaining an asymmetric distribution
      of Golgi resident glycosylation enzymes has been intensely debated in recent
      years. It is now clear that the targeting of Golgi resident enzymes is intimately
      associated with the organisation of Golgi membranes and the control of protein
      and lipid traffic in both anterograde and retrograde directions. Here we discuss
      the recent advances into how Golgi targeting signals of glycosylation enzymes
      function, and propose a model for maintaining the steady-state localisation of
      Golgi glycosyltransferases.

PMID- 11530210
TI  - Nucleotide sugar transporters: biological and functional aspects.
AB  - The Golgi apparatus serves as the major site of glycosylation reactions.
      Nucleotide sugars which are substrates of the Golgi localized
      glycosyltransferases are synthesized in the cytoplasm (cell nucleus in case of
      CMP-sialic acid) and must be transported into the compartment lumen. This
      transport function is carried out by nucleotide sugar transporters. The first
      genes were cloned in the year 1996 and revealed a family of structurally
      conserved multi-transmembrane-spanning proteins. Due to the high structural and
      functional conservation, the identification of many putative nucleotide sugar
      transporter sequences has become possible in the existing gene data bases and
      accelerates the increase in knowledge on structure-function-relationships. Recent
      developments in the nucleotide sugar transporter field are discussed in this
      article.

PMID- 11530211
TI  - Folding of the human immunodeficiency virus type 1 envelope glycoprotein in the
      endoplasmic reticulum.
AB  - The lumen of the endoplasmic reticulum (ER) provides a unique folding environment
      that is distinct from other organelles supporting protein folding. The relatively
      oxidizing milieu allows the formation of disulfide bonds. N-linked
      oligosaccharides that are attached during synthesis play multiple roles in the
      folding process of glycoproteins. They stabilize folded domains and increase
      protein solubility, which prevents aggregation of folding intermediates. Glycans
      mediate the interaction of newly synthesized glycoproteins with some resident ER
      folding factors, such as calnexin and calreticulin. Here we present an overview
      of the present knowledge on the folding process of the heavily glycosylated human
      immunodeficiency virus type 1 (HIV-1) envelope glycoprotein in the ER.

PMID- 11530212
TI  - Balancing N-linked glycosylation to avoid disease.
AB  - Complete loss of N-glycosylation is lethal in both yeast and mammals. Substantial
      deficiencies in some rate-limiting biosynthetic steps cause human congenital
      disorders of glycosylation (CDG). Patients have a range of clinical problems
      including variable degrees of mental retardation, liver dysfunction, and
      intestinal disorders. Over 60 mutations in phosphomannomutase (encoded by PMM2)
      diminish activity and cause CDG-Ia. The severe mutation R141H in PMM2 is lethal
      when homozygous, but heterozygous in about 1/70 Northern Europeans. Another
      disorder, CDG-Ic, is caused by mutations in ALG6, an alpha 1,3glucosyl
      transferase used for lipid-linked precursor synthesis, yet some function
      compromising mutations occur at a high frequency in this gene also. Maintenance
      of seemingly deleterious mutations implies a selective advantage or positive
      heterosis. One possible explanation for this is that production of infective
      viruses such as hepatitis virus B and C, or others that rely heavily on host N
      glycosylation, is substantially inhibited when only a tiny fraction of their coat
      proteins is misglycosylated. In contrast, this reduced glycosylation does not
      affect the host. Prevalent functional mutations in rate-limiting glycosylation
      steps could provide some resistance to viral infections, but the cost of this
      insurance is CDG. A balanced glycosylation level attempts to accommodate these
      competing agendas. By assessing the occurrence of a series of N-glycosylation
      compromising alleles in multi-genic diseases, it may be possible to determine
      whether impaired glycosylation is a risk factor or a major determinant underlying
      their pathology.

PMID- 11530213
TI  - Regulation of Paramecium primaurelia glycosylphosphatidyl-inositol biosynthesis
      via dolichol phosphate mannose synthesis.
AB  - A set of glycosylinositol-phosphoceramides, belonging to a family of
      glycosylphosphatidyl-inositols (GPIs) synthesized in a cell-free system prepared
      from the free-living protozoan Paramecium primaurelia has been described. The
      final GPI precursor was identified and structurally characterized as:
      ethanolamine-phosphate-6Man alpha 1-2Man alpha 1-6(mannosylphosphate) Man alpha 1
      4glucosamine-inositol-phospho-ceramide. During our investigations on the
      biosynthesis of the acid-labile modification, the additional mannosyl phosphate
      substitution, we observed that the use of the nucleotide triphosphate analogue
      GTP gamma S (guanosine 5-O-(thiotriphosphate)) blocks the biosynthesis of the
      mannosylated GPI glycolipids. We show that GTP gamma S inhibits the synthesis of
      dolichol-phosphate-mannose, which is the donor of the mannose residues for GPI
      biosynthesis. Therefore, we investigated the role of GTP binding regulatory 'G'
      proteins using cholera and pertussis toxins and an intracellular second messenger
      cAMP analogue, 8-bromo-cAMP. All the data obtained suggest the involvement of
      classical heterotrimeric G proteins in the regulation of GPI-anchor biosynthesis
      through dolichol-phosphate-mannose synthesis via the activation of adenylyl
      cyclase and protein phosphorylation. Furthermore, our data suggest that GTP gamma
      S interferes with synthesis of dolichol monophosphate, indicating that the
      dolichol kinase is regulated by the heterotrimeric G proteins.

PMID- 11530214
TI  - Heparan sulfate: anchor for viral intruders?
AB  - Heparan sulfates (HS) are ubiquitous, polyanionic carbohydrate chains linked to
      core proteins in cell membranes and extracellular matrices of all eukaryotes. Due
      to the complex nature of the HS-biosynthesis, a wealth of different structures
      are produced. These seem to have a well defined distribution in different tissues
      and cells throughout development. Binding of endogenous proteins with different
      functional properties such as growth factors, adhesion molecules or enzymes, is
      one of the functions of HS. Besides interaction with endogenous factors,
      glycosaminoglycans (GAG) and especially HS have also been demonstrated to
      function as receptors for a number of different pathogens. What roles may HS play
      in the pathogenesis and tropism of different intruders like parasites or viruses?
      What implications does binding of viruses to HS have for the development of drugs
      or the application of viral vectors for gene targeting? In this review an attempt
      is made to collect our present knowledge on viral usage of HS and the
      implications that follow.

PMID- 11530215
TI  - Hexuronyl C5-epimerases in alginate and glycosaminoglycan biosynthesis.
AB  - The sugar residues in most polysaccharides are incorporated as their
      corresponding monomers during polymerization. Here we summarize the three known
      exceptions to this rule, involving the biosynthesis of alginate, and the
      glycosaminoglycans, heparin/heparan sulfate and dermatan sulfate. Alginate is
      synthesized by brown seaweeds and certain bacteria, while glycosaminoglycans are
      produced by most animal species. In all cases one of the incorporated sugar
      monomers are being C5-epimerized at the polymer level, from D-mannuronic acid to
      L-guluronic acid in alginate, and from D-glucuronic acid to L-iduronic acid in
      glycosaminoglycans. Alginate epimerization modulates the mechanical properties of
      seaweed tissues, whereas in bacteria it seems to serve a wide range of purposes.
      The conformational flexibility of iduronic acid units in glycosaminoglycans
      promotes apposition to, and thus functional interactions with a variety of
      proteins at cell surfaces and in the extracellular matrix. In the bacterium
      Azotobacter vinelandii the alginates are being epimerized at the cell surface or
      in the extracellular environment by a family of evolutionary strongly related
      modular type and Ca(2+)-dependent epimerases (AlgE1-7). Each of these enzymes
      introduces a specific distribution pattern of guluronic acid residues along the
      polymer chains, explaining the wide structural variability observed in alginates
      isolated from nature. Glycosaminoglycans are synthesized in the Golgi system,
      through a series of reactions that include the C5-epimerization reaction along
      with extensive sulfation of the polymers. The single, Ca(2+)-independent,
      epimerase in heparin/heparan sulfate biosynthesis and the Ca(2+)-dependent
      dermatan sulfate epimerase(s) also generate variable epimerization patterns,
      depending on other polymer-modification reactions. The alginate and heparin
      epimerases appear unrelated at the amino acid sequence level, and have probably
      evolved through independent evolutionary pathways; however, hydrophobic cluster
      analysis indicates limited similarity. Seaweed alginates are widely used in
      industry, while heparin is well established in the clinic as an anticoagulant.

PMID- 11530216
TI  - Molecular properties and involvement of heparanase in cancer progression and
      normal development.
AB  - Heparan sulfate proteoglycans (HSPGs) play a key role in the self-assembly,
      insolubility and barrier properties of basement membranes and extracellular
      matrices. Hence, cleavage of heparan sulfate (HS) affects the integrity and
      functional state of tissues and thereby fundamental normal and pathological
      phenomena involving cell migration and response to changes in the extracellular
      microenvironment. Here, we describe the molecular properties, expression and
      function of a human heparanase, degrading HS at specific intrachain sites. The
      enzyme is synthesized as a latent approximately 65 kDa protein that is processed
      at the N-terminus into a highly active approximately 50 kDa form. The heparanase
      mRNA and protein are preferentially expressed in metastatic cell lines and human
      tumor tissues. Overexpression of the heparanase cDNA in low-metastatic tumor
      cells conferred a high metastatic potential in experimental animals, resulting in
      an increased rate of mortality. The heparanase enzyme also releases ECM-resident
      angiogenic factors in vitro and its overexpression induces an angiogenic response
      in vivo. Heparanase may thus facilitate both tumor cell invasion and
      neovascularization, both critical steps in cancer progression. The enzyme is also
      involved in cell migration associated with inflammation and autoimmunity. The
      unexpected identification of a single predominant functional heparanase suggests
      that the enzyme is a promising target for drug development. In fact, treatment
      with heparanase inhibitors markedly reduces tumor growth, metastasis and
      autoimmune disorders in animal models. Studies are underway to elucidate the
      involvement of heparanase in normal processes such as implantation, embryonic
      development, morphogenesis, tissue repair, inflammation and HSPG turnover.
      Heparanase is the first functional mammalian HS-degrading enzyme that has been
      cloned, expressed and characterized. This may lead to identification and cloning
      of other glycosaminoglycan degrading enzymes, toward a better understanding of
      their involvement and significance in normal and pathological processes.

PMID- 11530217
TI  - Glycan mimicry as a basis for novel anti-infective drugs.
AB  - The idea of using carbohydrate-based drugs to prevent attachment of microbial
      pathogens to host tissues has been around for about three decades. This concept
      evolved from the observation that many pathogenic microbes bind to complex
      carbohydrate sequences on the surface of host cells. It stands to reason,
      therefore, that analogs of the carbohydrate sequences pathogens bind to could be
      used to competitively inhibit these interactions, thereby preventing microbial
      damage to the host. This article will summarize some of the recent advances in
      developing such carbohydrate-based anti-infective drugs.

PMID- 11530218
TI  - Neurogenesis in the olfactory bulb of adult zebrafish.
AB  - Cell genesis in the adult brain of zebrafish, with specific reference to the
      olfactory bulbs, was examined using bromodeoxyuridine immunocytochemistry. Mature
      fish were exposed to a 1% solution of the thymidine analog 5-bromo-2'
      deoxyuridine for 1 h and then killed after short (4-h) or long (3-4-week)
      survival periods. A monoclonal antibody to bromodeoxyuridine allowed
      visualization of cells that incorporated the drug during the S phase of mitosis.
      Four hours after administration of the drug, antibody-labeled cells were found
      almost exclusively in the proliferative zones around the ventricles and in the
      cerebellum. Very few labeled nuclei were seen in other locations in the brain,
      indicating that cell genesis occurs in discrete regions in adults. The few
      labeled profiles in the olfactory bulbs were located in the olfactory nerve
      layer; these profiles had the morphology of glial nuclei and did not stain with a
      neuronal marker, the Hu antibody. After longer survival times, labeled cells were
      present throughout the layers of the olfactory bulb, and many of the
      immunoreactive profiles in the internal cell layer were also labeled with the Hu
      antibody, indicating that they are likely adult-formed interneurons. Thus,
      neurogenesis continues in the olfactory bulb of adult zebrafish. Understanding
      the process of the generation of new neurons in the brain of adult animals can
      lead to important insights into neural regeneration and adult plasticity.

PMID- 11530219
TI  - GABA-mediated synchronization in the human neocortex: elevations in extracellular
      potassium and presynaptic mechanisms.
AB  - Field potential and extracellular [K(+)] ([K(+)](o)) recordings were made in the
      human neocortex in an in vitro slice preparation to study the synchronous
      activity that occurs in the presence of 4-aminopyridine (50 microM) and
      ionotropic excitatory amino acid receptor antagonists. Under these experimental
      conditions, negative or negative-positive field potentials accompanied by rises
      in [K(+)](o) (up to 4.1 mM from a baseline of 3.25 mM) occurred spontaneously at
      intervals of 3-27 s. Both field potentials and [K(+)](o) elevations were largest
      at approximately 1000 microm from the pia. Similar events were induced by
      neocortical electrical stimuli. Application of medium containing low
      [Ca(2+)]/high [Mg(2+)] (n=3 slices), antagonism of the GABA(A) receptor (n=7) or
      mu-opioid receptor activation (n=4) abolished these events. Hence, they
      represented network, GABA-mediated potentials mainly reflecting the activation of
      type A receptors following GABA release from interneurons. The GABA(B) receptor
      agonist baclofen (10-100 microM, n=11) reduced and abolished the GABA-mediated
      potentials (ID(50)=18 microM). Baclofen effects were antagonized by the GABA(B)
      receptor antagonist CGP 35348 (0.1-1 mM, n=6; ID(50)=0.19 mM). CGP 38345
      application to control medium increased the amplitude of the GABA-mediated
      potentials and the concomitant [K(+)](o) rises without modifying their rate of
      occurrence. The GABA-mediated potentials were not influenced by the broad
      spectrum metabotropic glutamate agonist (+/-)-1-aminocyclopentane-trans-1,3
      dicarboxylic acid (100 microM, n=10), but decreased in rate with the group I
      receptor agonist (S)-3,5-dihydroxyphenylglycine (10-100 microM, n=9). Our data
      indicate that human neocortical networks challenged with 4-aminopyridine generate
      glutamatergic-independent, GABA-mediated potentials that are modulated by mu
      opioid and GABA(B) receptors presumably located on interneuron terminals. These
      events are associated with [K(+)](o) elevations that may contribute to
      interneuron synchronization in the absence of ionotropic excitatory synaptic
      transmission.

PMID- 11530220
TI  - Evidence that integrins contribute to multiple stages in the consolidation of
      long term potentiation in rat hippocampus.
AB  - Three structurally distinct groups of antagonists were used to test the
      hypothesis that integrin adhesion receptors play an essential role in
      consolidating (stabilizing) long term potentiation of the Schaffer collaterals in
      rat hippocampus. Comparisons were made of percent potentiation at antagonist
      treated versus control sites within CA1 stratum radiatum of the same hippocampal
      slice. Function blocking antibodies against the alpha5 subunit of the fibronectin
      receptor had no effect on baseline responses or initial potentiation but resulted
      in a >30% reduction, relative to within-slice control long term potentiation, 45
      min later. Larger reductions were recorded in separate experiments continued for
      4 h after the induction of potentiation. Alpha(v) and alpha2 subunit antibodies
      did not reliably affect the stabilization of potentiation. An antagonist peptide
      with preference for beta1 integrins produced a slowly developing decline of the
      type seen with alpha5 antibodies. A cyclic peptide antagonist reduced
      potentiation within 10 min of induction and caused an almost 40% decrease over 45
      min. Two disintegrins (snake toxins that potently block integrins) were very
      effective in preventing the consolidation of long term potentiation: echistatin
      reduced potentiation by >70%, while triflavin caused approximately 50% decrease.
      The suppressing effects of echistatin were concentration-dependent, obtained with
      treatment after induction, and much more rapid than the effects of antibodies.
      Rapid declines in potentiation were particularly evident when the two
      disintegrins were applied together. These results indicate that hippocampal
      fibronectin receptors (alpha5/beta1 integrin) contribute importantly to a slowly
      developing phase of long term potentiation consolidation. They also suggest that
      other integrins are critical to aspects of consolidation occurring in the first
      few minutes after induction.

PMID- 11530221
TI  - Cell formation in the human hippocampal formation from mid-gestation to the late
      postnatal period.
AB  - In the present study cell formation was studied in the human hippocampal
      formation from the 24th gestational week until the end of the first postnatal
      year. Proliferating cells were detected with the monoclonal antibody MIB-1. The
      cytoarchitectonic layers of Ammon's horn are formed before the 24th gestational
      week. In harmony with this observation, cell proliferation in the hippocampal
      ventricular zone is minimal after the 24th week. In addition, local cell
      multiplication in Ammon's horn is occasional and the proliferating cells are
      glial or endothelial cells. In contrast, cell formation continues in the hilar
      region of the dentate gyrus even after birth. Immature cells accumulate in the
      hilus, and at the border between the hilus and the granule cell layer throughout
      the first eight postnatal months. The subgranular zone of the dentate gyrus
      becomes a cell sparse area at about the 11th postnatal month, indicating that
      immature cells from the hilus have already migrated to the granule cell layer and
      differentiated into granule cells. There is an increase in glial cell
      proliferation both in Ammon's horn and the dentate gyrus at the 11.5th postnatal
      month suggesting the onset of myelination by the end of the first year. Our
      findings indicate that most pyramidal neurons of Ammon's horn are generated in
      the first half of pregnancy and no pyramidal neurons are formed after the 24th
      gestational week. In contrast, granule cells of the dentate gyrus proliferate in
      a decreasing rate during the second half of pregnancy and after birth.
      Proliferating neuronal precursors occur in a low percentage in the dentate gyrus
      of 3-, 5- and 11.5-month-old children.

PMID- 11530222
TI  - Amyloid beta-protein fragment 31-35 forms ion channels in membrane patches
      excised from rat hippocampal neurons.
AB  - Inside-out membrane patches excised from rat hippocampal neurons were used to
      test if ion channels could be formed by fragment 31-35 of amyloid beta-protein.
      The results showed: (1) after application of fragment 31-35 of amyloid beta
      protein (5 microM) to either the inner or outer side of the patches, spontaneous
      currents could be recorded from those patches that had previously been 'silent';
      (2) the fragment 31-35-induced conductance was cation-selective with a
      permeability ratio of P(Cs)/P(Cl)=23; (3) different levels of conductance,
      ranging from 25 to 500 pS, could be recorded in different patches, and in some
      cases, different conductances and spontaneous transitions among them could be
      recorded in a single patch; and (4) application of ZnCl(2) (1 mM) to the inner
      side of the patches reversibly blocked the newly formed channel activity; a
      similar effect was observed after application of CdCl(2) (1 mM). These results
      show that fragment 31-35 of amyloid beta-protein can insert into membrane patches
      from both sides and form cation-selective, Zn(2+)- and Cd(2+)-sensitive ion
      channels. It is proposed that fragment 31-35 in amyloid beta-protein might be the
      shortest active sequence known to date to form ion channels across neuronal
      membranes.

PMID- 11530224
TI  - Nucleus accumbens dopamine depletions make animals highly sensitive to high fixed
      ratio requirements but do not impair primary food reinforcement.
AB  - It has been suggested that dopamine in nucleus accumbens is involved in the
      process of enabling organisms to overcome work-related response costs. One way of
      controlling work costs with operant schedules is to use fixed ratio schedules
      with different ratio requirements. In the present study, the effects of nucleus
      accumbens dopamine depletions were investigated using six schedules: fixed ratio
      5, 20, 50, 100, 200, and 300. In the first three schedules the food reinforcement
      consisted of one 45 mg food pellet per ratio completed. In the remaining
      schedules the food reinforcement per ratio completed was increased to two pellets
      for fixed ratio 100, four pellets for fixed ratio 200, and six pellets for fixed
      ratio 300. All rats were trained extensively prior to surgery, and rats were able
      to maintain high levels of responding on all schedules up to the fixed ratio 300.
      After training, rats were injected with either ascorbate vehicle or 6
      hydroxydopamine into the nucleus accumbens. Rats were tested post-surgically on
      each of the schedules, with 3 days of testing per schedule. Rats with nucleus
      accumbens dopamine depletions exhibited behavioral deficits that were highly
      dependent upon the ratio value. There were small and transient effects of
      dopamine depletion on fixed ratio 5 lever pressing, but as the ratio value got
      larger the impairment became greater. On the fixed ratio 20 and 50 schedules,
      response rates were partially reduced in dopamine-depleted rats. Responding on
      the fixed ratio 200 and 300 schedules was severely impaired, and on the last day
      of fixed ratio 300 testing no dopamine-depleted rats obtained a single
      reinforcer. These data are consistent with previous reports that accumbens
      dopamine depletions enhance 'ratio strain', making rats more sensitive to high
      ratio values. The induction of ratio strain by dopamine depletions does not
      appear to be related to a loss of appetite, and seems to be relatively
      independent of the baseline rate of responding and the overall density of food
      reinforcement across the session. We conclude that dopamine in nucleus accumbens
      may be important for enabling rats to overcome behavioral constraints such as
      work-related response costs, and may be critical for the behavioral organization
      and conditioning processes that enable animals to emit large numbers of responses
      in the absence of primary reinforcement.

PMID- 11530223
TI  - Resistance of the dentate gyrus to induced apoptosis during ageing is associated
      with increases in transforming growth factor-beta1 messenger RNA.
AB  - Up-regulation of endogenous neurotrophic factors may protect against apoptosis
      during ageing. Recent studies showed that the expression of several neurotrophic
      factors increased with age in specific regions of the rat brain. Previously, we
      showed that removal of trophic adrenal steroids by adrenalectomy induced
      apoptosis in the dentate gyrus of adult rats, which was accompanied by increased
      expression of transforming growth factor-beta1 (TGF-beta1) messenger RNA. In this
      study, we compared the relative densities of apoptotic cells in the dentate gyrus
      with TGF-beta1 messenger RNA expression in virgin male Fischer 344 rats ranging
      from 2 to 26 months of age across three treatment groups: adrenalectomy,
      adrenalectomy with corticosterone replacement, or sham operation. Seven days
      after adrenalectomy an increase in the density of apoptotic cells was observed in
      rats of all age groups compared with sham-operated and corticosterone-treated
      groups. By in situ hybridisation, the glial messenger RNAs, TGF-beta1 and glial
      fibrillary acidic protein as a marker of ageing, increased following
      adrenalectomy in the dentate gyrus in rats of all ages compared with control
      groups. Interestingly, within adrenalectomy groups, both the number and density
      of apoptotic cells decreased significantly by 6-8 months with a further decrease
      at 24-26 months of age. Furthermore, the amount of apoptosis corresponded to
      changes in TGF-beta1 expression, notably in: (i) adrenalectomised rats showing a
      significant inverse correlation and (ii) 24-26-month-old rats with the lowest
      induced apoptosis showing increased expression at the time of adrenalectomy.
      These studies show that resistance to adrenalectomy-induced apoptosis in the
      dentate gyrus is associated with increases in TGF-beta1 messenger RNA expression.
      Furthermore, the endogenous up-regulation of neurotrophic factors, such as the
      increase in TGF-beta1 expression in the oldest rats, suggests that the aged brain
      may have compensatory mechanisms, which protect against apoptosis.

PMID- 11530225
TI  - Neostriatal and globus pallidus stimulation induced inhibitory postsynaptic
      potentials in entopeduncular neurons in rat brain slice preparations.
AB  - Recent anatomical studies revealed that the entopeduncular nucleus of the rat
      receives GABAergic inputs from both the neostriatum and the globus pallidus. The
      present study was undertaken to reveal the physiological features of these inputs
      using the intracellular recording method in rat brain slice preparations. Most of
      the entopeduncular nucleus neurons generated repetitive firing without spike
      accommodation with intracellular current stimulation and thus were classified as
      Type-I. A small number of neurons were classified as Type-II since they generated
      spikes with pronounced accommodation. Most of the Type-I, but none of Type-II,
      entopeduncular nucleus neurons exhibited monosynaptic GABAergic inhibitory
      postsynaptic potentials (IPSPs) after stimulation of the neostriatum and the
      globus pallidus. Neostriatal stimulation induced long latency IPSPs while
      pallidal stimulation induced long latency IPSPs compounded with short latency
      IPSPs. The IPSPs were mediated by GABA(A) receptors. The unitary IPSPs to
      striatal stimulation were small while those to pallidal stimulation were large in
      amplitude and able to reset ongoing rhythmic firing. The short latency IPSPs
      induced by pallidal stimulation reversed at a somatic membrane potential that was
      a few millivolts more depolarized than the long latency IPSPs, suggesting that
      the striatal inputs were evoked in more distal portions of the neurons than the
      pallidal inputs. Repetitive activation of these inputs resulted in a poor
      amplitude summation but a prolongation of the duration of the IPSPs. The results
      of the present study indicate that the pallidal projection to the entopeduncular
      nucleus is physiologically significant and that the neostriatum and the globus
      pallidus play important roles in controlling the activity of the entopeduncular
      nucleus, although in different ways.

PMID- 11530226
TI  - Activation of metabotropic glutamate receptor 1 inhibits glutamatergic
      transmission in the substantia nigra pars reticulata.
AB  - The substantia nigra pars reticulata is a primary output nucleus of the basal
      ganglia motor circuit and is controlled by a fine balance between excitatory and
      inhibitory inputs. The major excitatory input to GABAergic neurons in the
      substantia nigra arises from glutamatergic neurons in the subthalamic nucleus,
      whereas inhibitory inputs arise mainly from the striatum and the globus pallidus.
      Anatomical studies revealed that metabotropic glutamate receptors (mGluRs) are
      highly expressed throughout the basal ganglia. Interestingly, mRNA for group I
      mGluRs are abundant in neurons of the subthalamic nucleus and the substantia
      nigra pars reticulata. Thus, it is possible that group I mGluRs play a role in
      the modulation of glutamatergic synaptic transmission at excitatory
      subthalamonigral synapses. To test this hypothesis, we investigated the effects
      of group I mGluR activation on excitatory synaptic transmission in putative
      GABAergic neurons in the substantia nigra pars reticulata using the whole cell
      patch clamp recording approach in slices of rat midbrain. We report that
      activation of group I mGluRs by the selective agonist (R,S)-3,5
      dihydroxyphenylglycine (100 microM) decreases synaptic transmission at excitatory
      synapses in the substantia nigra pars reticulata. This effect is selectively
      mediated by presynaptic activation of the group I mGluR subtype, mGluR1.
      Consistent with these data, electron microscopic immunocytochemical studies
      demonstrate the localization of mGluR1a at presynaptic sites in the rat
      substantia nigra pars reticulata. From this finding that group I mGluRs modulate
      the major excitatory inputs to GABAergic neurons in the substantia nigra pars
      reticulata we suggest that these receptors may play an important role in basal
      ganglia functions. Studying this effect, therefore, provides new insights into
      the modulatory role of glutamate in basal ganglia output nuclei in physiological
      and pathophysiological conditions.

PMID- 11530227
TI  - Spontaneous circling behavior and dopamine neuron loss in a genetically
      hypothyroid mouse.
AB  - The genetically hypothyroid mouse, Tshr(hyt), has a single point mutation
      resulting in a defective thyroid-stimulating hormone receptor, and therefore a
      non-functional thyroid gland. This is an autosomal recessive disorder and
      affected mice have been reported to have a number of somatic and behavioral
      deficits. This study reports a pronounced, spontaneous, asymmetrical circling
      behavior in the Tshr(hyt) mouse. The spontaneous circling behavior appeared in
      about 25% of the homozygous animals, in both males and females. The circling
      usually appeared by postnatal day 35 and continued throughout the lifespan of the
      animal. The circling was in one direction only, either clockwise or
      counterclockwise, with the directional preference being almost absolute. A
      stereological analysis of tyrosine hydroxylase immunoreactive neurons in the
      substantia nigra and adjacent ventral tegmental area of circling homozygous mice,
      non-circling homozygous mice and heterozygous mice revealed that the circlers had
      significantly fewer (40% reduction) midbrain dopamine neurons than those animals
      that did not circle. There was not an association between the direction of the
      circling and an asymmetry in the number of dopamine neurons in the midbrains of
      these mice. There was no difference in the number of dopamine neurons in the
      midbrain of the homozygous non-circlers and the heterozygous mice. These studies
      indicate that about 25% of genetically hypothyroid mice demonstrated a
      spontaneous, perseverative, unilateral circling behavior that was associated with
      a significant reduction in the number of their midbrain dopamine neurons. Thus
      congenitally hypothyroid mice are at risk for a reduction in the number of nigral
      dopamine neurons and an associated repetitive movement disorder.

PMID- 11530228
TI  - Dissociation between the attentional functions mediated via basal forebrain
      cholinergic and GABAergic neurons.
AB  - The role of basal forebrain corticopetal cholinergic projections in attentional
      functions has been extensively investigated. For example, 192 IgG-saporin-induced
      loss of cortical cholinergic inputs was repeatedly demonstrated to result in a
      selective impairment in the ability of rats to detect signals in a task designed
      to assess sustained attention performance. The loss of cortical cholinergic
      inputs correlated highly with the decrease in the hit rate. Little is known about
      the functions of basal forebrain non-cholinergic neurons, particularly
      corticopetal GABAergic neurons, largely because of the absence of specific
      research tools to manipulate selectively this projection. As basal forebrain
      lesions produced with ibotenic acid were previously observed to potently destroy
      non-cholinergic, particularly GABAergic neurons while producing only moderate
      decreases in the density of cortical cholinergic inputs, the present experiment
      examined the effects of such lesions on sustained attention performance and then
      compared these effects with the immunohistochemical and attentional consequences
      of selective cholinotoxic lesions produced by intra-basal forebrain infusions of
      192 IgG-saporin. In contrast to the selective decrease in hits previously
      observed in 192 IgG-saporin-lesioned animals, the attentional performance of
      ibotenic acid-lesioned animals was characterized by a selective increase in the
      relative number of false alarms, that is 'claims' for signals in non-signal
      trials. Analyses of the response latencies suggested that this effect of ibotenic
      acid was due to impairments in the animals' ability to switch from the processing
      of the response rules for signal trials to those for non-signal trials. As
      expected, 192 IgG-saporin did not affect the number of basal forebrain
      parvalbumin-positive neurons, that are presumably GABAergic, but decreased
      cortical acetylcholinesterase-positive fiber density by over 80%. Conversely, in
      ibotenic acid-lesioned animals, basal forebrain parvalbumin-positive cells were
      decreased by 60% but cortical acetylcholinesterase-positive fiber density was
      only moderately reduced (less than 25%). These data form the basis for the
      development of the hypothesis that basal forebrain GABAergic neurons mediate
      executive aspects of attentional task performance. Such a function may be
      mediated in parallel via basal forebrain GABAergic projections to the cortex and
      the subthalamic nucleus.

PMID- 11530230
TI  - Raphe magnus/pallidus neurons regulate tail but not mesenteric arterial blood
      flow in rats.
AB  - In urethane-anesthetized rats with body temperature maintained at 39-40 degrees
      C, electrical stimulation of raphe magnus/pallidus/parapyramidal region within
      0.5 mm of the ventral medullary surface reduced arterial blood flow to the tail
      cutaneous bed (measured with a chronically implanted Doppler ultrasonic
      flowmeter) from 28+/-5 to 6+/-1 cm/s (P<0.01), without changing mesenteric
      arterial blood flow, and with only small, variable changes in arterial pressure.
      Injection of bicuculline (50 pmol in 50 nl) at the same site reduced tail flow
      from 19+/-2 to 3+/-1 cm/s (P<0.01), again without significantly changing
      mesenteric flow, but with a moderate increase in arterial pressure. When the rat
      was cooled to reduce basal tail blood flow, injection of muscimol (1 nmol in 100
      nl) or GABA (100 nmol in 100 nl) into the raphe site restored tail blood flow to
      93+/-4% of the pre-cooling level. These recordings are the first reported direct
      measurements of rat tail blood flow changes elicited by alteration of neuronal
      function in the brainstem. The rostral medullary raphe controls the tail
      cutaneous vascular bed in a relatively selective manner. Our findings add to
      evidence that raphe magnus/pallidus/parapyramidal neurons are involved in
      regulating cutaneous blood flow in response to changes in body temperature in the
      rat.

PMID- 11530229
TI  - Corticotropin-releasing hormone messenger RNA distribution and stress-induced
      activation in the thalamus.
AB  - Corticotropin-releasing hormone plays a critical role in mediating the stress
      response. Brain circuits hypothesized to mediate stress include the thalamus,
      which plays a pivotal role in distributing sensory information to cortical and
      subcortical structures. In situ hybridization revealed neurons containing
      corticotropin-releasing hormone messenger RNA in the posterior thalamic nuclear
      group and the central medial nucleus of the thalamus, which interfaces with the
      ventral posteromedial nucleus (parvicellular part). These regions are of interest
      because they process somatosensory and visceral information. In the first
      experiment, the effect of acute stress on thalamic corticotropin-releasing
      hormone messenger RNA levels was assessed. Rats restrained for 1 h and killed 1 h
      later were found to have increased corticotropin-releasing hormone messenger RNA
      in the posterior thalamic nuclear group. The time course of these changes was
      examined in a second experiment in which rats were killed immediately or 3 h
      after restraint. While no changes occurred in the thalamus immediately after
      restraint, 3 h after restraint, increases in corticotropin-releasing hormone
      messenger RNA occurred in both the posterior thalamic nuclear group and the
      central medial-ventral posteromedial nucleus (parvicellular part) of the
      thalamus. A different pattern of activation was observed in the paraventricular
      nucleus of the hypothalamus with increased corticotropin-releasing hormone
      messenger RNA immediately after restraint, but not 1 or 3 h later. In addition to
      the stress-induced changes, a prominent decrease in baseline thalamic
      corticotropin-releasing hormone messenger RNA was observed from 1000 to 1300 h.
      These results show that the thalamus contains corticotropin-releasing hormone
      messenger RNA that increases after restraint stress, indicating a role for
      thalamic corticotropin-releasing hormone systems in the stress response. Stress
      induced changes in thalamic corticotropin-releasing hormone messenger RNA
      expression appears to be regulated differently than that in the paraventricular
      nucleus of the hypothalamus, and may be influenced by diurnal mechanisms.

PMID- 11530231
TI  - Long-term alterations in body weight do not affect the expression of melanocortin
      receptor-3 and -4 mRNA in the ovine hypothalamus.
AB  - The pro-opiomelanocortin-derived peptides and the melanocortin receptors are
      implicated in various functions within the CNS including the regulation of food
      intake. In the present study, we used in situ hybridization, with specific 35S
      labelled ovine riboprobes to map the expression of melanocortin receptor-3 (MC3
      R) and -4 (MC4-R) mRNA in the diencephalon and brainstem of normal female sheep.
      Furthermore, we examined the effect of long-term alterations in energy balance on
      the distribution and expression of MC3-R and MC4-R mRNA in food-restricted and ad
      libitum-fed ovariectomized female sheep. The distribution of melanocortin
      receptors generally resembled that of the rat. A high number of MC3-R-labelled
      cells were seen in the ventral division of the lateral septum and the medial
      preoptic area. In the hypothalamus, a moderate number of MC3-R-labelled cells was
      observed in the lateral hypothalamic area while other nuclear groups had low to
      intermediate numbers of MC3-R-labelled cells. The distribution of MC4-R mRNA was
      generally similar to that of MC3-R mRNA in the septal/preoptic and hypothalamic
      regions, with a high number of labelled cells present in the intermediate
      division of the lateral septum. Within the hypothalamus, no MC4-R mRNA expression
      was observed in the arcuate nucleus. There was more widespread distribution of
      moderate to low numbers of MC4-R mRNA-expressing cells in the brainstem compared
      to that of MC3-R mRNA. Unlike findings in the rat, only a low number of cells
      expressed melanocortin receptor mRNA in the ovine hypothalamic nuclei associated
      with feeding behavior. The number of melanocortin receptor-labelled cells and the
      level of expression (silver grains/cell) in the hypothalamic feeding centers was
      similar in food-restricted and ad libitum-fed animals. These findings suggest
      that long-term alterations in metabolic status do not change the melanocortin
      receptor mRNA distribution and/or expression in the sheep hypothalamus.

PMID- 11530232
TI  - Inhibitory zinc-enriched terminals in mouse spinal cord.
AB  - The ultrastructural localization of zinc transporter-3, glutamate decarboxylase
      and zinc ions in zinc-enriched terminals in the mouse spinal cord was studied by
      zinc transporter-3 and glutamate decarboxylase immunohistochemistry and zinc
      selenium autometallography, respectively. The distribution of zinc selenium
      autometallographic silver grains, and zinc transporter-3 and glutamate
      decarboxylase immunohistochemical puncta in both ventral and dorsal horns as seen
      in the light microscope corresponded to their presence in the synaptic vesicles
      of zinc-enriched terminals at ultrastructural levels. The densest populations of
      zinc-enriched terminals were seen in dorsal horn laminae I, III and IV, whereas
      the deeper laminae V and VI contained fewer terminals. At ultrastructural levels,
      zinc-enriched terminals primarily formed symmetrical synapses on perikarya and
      dendrites. Only relatively few asymmetrical synapses were observed on zinc
      enriched terminals. In general, the biggest zinc-enriched terminals contacted
      neuronal somata and large dendritic elements, while medium-sized and small
      terminals made contacts on small dendrites. The ventral horn was primarily
      populated by big and medium-sized zinc-enriched terminals, whereas the dorsal
      horn was dominated by medium-sized and small zinc-enriched terminals. The
      presence of boutons with flat synaptic vesicles with zinc ions and symmetric
      synaptic contacts suggests the presence of inhibitory zinc-enriched terminals in
      the mammalian spinal cord, and this was confirmed by the finding that zinc ions
      and glutamate decarboxylase are co-localized in these terminals. The pattern of
      zinc-enriched boutons in both dorsal and ventral horns is compatible with
      evidence suggesting that zinc may be involved in both sensory transmission and
      motor control.

PMID- 11530233
TI  - Heme oxygenase inhibitors reduce formalin-induced Fos expression in mouse spinal
      cord tissue.
AB  - Recent work from our laboratory and others supports a role for heme oxygenase in
      nociception and pain of several etiologies including inflammatory, incisional and
      neuropathic. Since it has been observed that heme oxygenase inhibitors reduce
      formalin-induced pain behaviors in mice and rats, we attempted to determine if
      this analgesic effect was reflected in a reduction in formalin-induced spinal
      cord Fos expression, an index of neuronal activation. To perform these studies,
      it was necessary to first examine the cytoarchitecture of the mouse lumbar spinal
      cord so that histological sections from known segmental levels could be chosen,
      and Fos-positive nuclei could be assigned to established dorsal horn laminae.
      After documenting the segmental and laminar distribution of Fos-positive nuclei
      following a 5% formalin injection, we went on to determine that the heme
      oxygenase inhibitor tin-protoporphyrin or morphine reduced this Fos expression as
      analyzed using confocal fluorescence microscopy. It was also observed that mice
      lacking expression of heme oxygenase type 2, an isozyme of heme oxygenase found
      in high abundance in the spinal cord, had lowered Fos expression after the
      formalin injection. Additional confocal microscopy studies demonstrated
      widespread expression of heme oxygenase type 2 in spinal cord neuron cell bodies.
      Double-labeling experiments showed that a high percentage of Fos-positive nuclei
      identified after administration of formalin were located within heme oxygenase
      type 2-positive cell profiles. Our studies support the hypothesis that heme
      oxygenase type 2 plays a role in formalin-induced nociception. Furthermore, from
      these results we suggest that the heme oxygenase type 2 located in spinal cord
      dorsal horn neurons participates in this nociceptive pathway.

PMID- 11530234
TI  - Localization of metabotropic glutamate receptors 2/3 on primary afferent axons in
      the rat.
AB  - The goal of the present study is to determine the relationship of metabotropic
      glutamate receptors 2/3 (mGluR2/3) to dorsal root ganglion cells, peripheral
      primary afferent fibers in digital nerves and central primary afferent fibers in
      the spinal cord. We demonstrate that approximately 40% of L4 and L5 dorsal root
      ganglion cells contain mGluR2/3-like immunoreactivity. These mGluR2/3-positive
      cells are small in diameter (23 microm) and 76% stain for the isolectin Griffonia
      simplicifolia (I-B4), while 67% of I-B4 cells have mGluR2/3-like
      immunoreactivity. Electron microscopic analyses of mGluR2/3-like immunoreactivity
      in axons in digital nerves indicate that 32% of unmyelinated and 28% of
      myelinated axons are labeled. In the lumbar dorsal horn, mGluR2/3-like
      immunoreactivity is localized preferentially in lamina IIi with lighter staining
      in laminae III and IV. The dense mGluR2/3-like immunoreactivity in lamina IIi is
      consistent with the localization of these receptors in I-B4-labeled dorsal root
      ganglion cells. Elimination of primary afferent input following unilateral dorsal
      rhizotomies significantly decreases the mGluR2/3-like immunoreactivity density in
      the dorsal horn although some residual staining does remain, suggesting that many
      but not all of these receptors are located on primary afferent processes. The
      finding that mGluR2/3s are located on peripheral sensory axons suggests that they
      are involved in peripheral sensory transduction and can modulate transmission of
      sensory input before it reaches the spinal cord. This offers the possibility of
      altering sensory input, particularly noxious input, at a site that would avoid
      CNS side effects. Since many but not all of these receptors are located on
      primary afferent terminals, these receptors may also influence primary afferent
      transmission in the dorsal horn through presynaptic mechanisms and glutamatergic
      transmission in general through both presynaptic and postsynaptic mechanisms.
      Since these receptors are concentrated in lamina IIi and also largely co
      localized with I-B4, they may have considerable influence on nociceptive
      processing by what are considered to be non-peptidergic primary afferent neurons.

PMID- 11530235
TI  - Interleukin 1-induced cyclooxygenase and nitric oxide synthase gene expression in
      the rat dorsal root ganglia is modulated by antioxidants.
AB  - Interleukin 1beta induced both nitric oxide synthase 2 (NOS-2) and cyclooxygenase
      2 (COX-2) gene expression in dorsal root ganglion explant culture with increased
      NOS-2 and COX-2 activities, and corresponding increases in the production of
      nitric oxide and prostaglandin E(2). The proinflammatory cytokine also increased
      8-isoprostaglandin F(2alpha) concentration, an index of oxidant stress-mediated
      production of lipid hydroperoxides/reactive oxygen species. The signaling
      mechanisms by which interleukin 1beta regulates NOS-2 and COX-2 genes remain
      obscure. Reactive oxygen species play an important role in inflammatory processes
      as mediators of injury, and potentially as intracellular signaling molecules in
      interleukin 1beta-mediated regulation of gene expression. The effects of
      antioxidants that act by different mechanisms on interleukin 1beta-mediated NOS-2
      and COX-2 gene expression were studied in rat dorsal root ganglion explants. The
      oxidant scavenger pyrrolidine dithiocarbamate abolished interleukin 1beta-induced
      NOS-2 mRNA accumulation and decreased nitric oxide production in a concentration
      dependent manner, thus indicating that this antioxidant decreased either the
      transcription of NOS-2 gene or the stability of NOS-2 mRNA. In contrast,
      pyrrolidine dithiocarbamate significantly inhibited COX-2 gene expression at the
      posttranscriptional level, since pyrrolidine dithiocarbamate did not affect
      interleukin 1beta-induced COX-2 mRNA transcripts but inhibited COX-2 protein
      expression and prostaglandin E(2) production. Rotenone, another antioxidant that
      attenuates reactive oxygen species production by inhibiting the mitochondrial
      electron transport system, failed to inhibit interleukin 1beta-induced NOS-2 and
      COX-2 mRNA-encoding transcripts. However, rotenone inhibited NOS-2 and COX-2
      proteins and associated nitric oxide and prostaglandin E(2) production,
      respectively, suggesting a posttranscriptional target for interleukin 1beta
      mediated regulation of NOS-2 and COX-2 gene expression. Furthermore, both
      pyrrolidine dithiocarbamate and rotenone also decreased interleukin 1beta-induced
      8-isoprostaglandin F(2alpha) production. These results indicate that not only
      transcriptional regulation, but also posttranscriptional events are involved in a
      redox-sensitive regulation of interleukin 1beta-induced NOS-2 and COX-2 gene
      expression in the dorsal root ganglia. Overall, interleukin 1beta-induced oxidant
      stress appears to regulate NOS-2 and COX-2 gene expression primarily at the level
      of protein translation. By implicating reactive oxygen species production in
      interleukin-1beta receptor-activated molecular signaling in the dorsal root
      ganglia, our data suggest a possible novel target for intervention in cytokine
      mediated inflammatory processes.

PMID- 11530237
TI  - Degeneration of neurons and glia in the Niemann-Pick C mouse is unrelated to the
      low-density lipoprotein receptor.
AB  - The BALB/c mouse model of Niemann-Pick type C disease exhibits similar
      neuropathological features to the human condition, including cerebral atrophy,
      demyelination of the corpus callosum, and degeneration of cerebellar Purkinje
      cells. The gene defect in Niemann-Pick C disease causes cholesterol to accumulate
      within the lysosomal compartment of neurons and glial cells. In order to
      determine whether cholesterol accumulation through the low-density lipoprotein
      receptor pathway plays an important role in the degenerative process, Niemann
      Pick C mice were crossed with low-density lipoprotein receptor knockout mice. The
      purpose of the present study was to determine whether degeneration of neurons and
      glial cells is reduced in Niemann-Pick C animals lacking the low-density
      lipoprotein receptor. Using stereological counting methods, Purkinje cells were
      counted in the cerebellum and glial cell bodies were counted in the corpus
      callosum in mice at 3, 7.5 and 11 weeks of age. In the Niemann-Pick C animals,
      compared to wild-type control mice, there were 48% fewer glial cells at 3 weeks
      of age, and by 11 weeks of age there were 63% fewer glial cells. Purkinje cells
      were decreased in number by 13% at 3 weeks of age, and by 11 weeks of age there
      was a 96% loss. In the Niemann-Pick C animals lacking low-density lipoprotein
      receptors, there was no difference in the magnitude of glial cell or Purkinje
      cell loss compared to the Niemann-Pick C animals. These data indicate that both
      neurons and glia are vulnerable to degeneration in the Niemann-Pick C mouse, but
      that blocking the accumulation of cholesterol through the low-density lipoprotein
      receptor pathway does not alter the degenerative phenotype of Niemann-Pick C
      disease.

PMID- 11530236
TI  - Altered effects of ethanol in NR2A(DeltaC/DeltaC) mice expressing C-terminally
      truncated NR2A subunit of NMDA receptor.
AB  - Phosphorylation of C-termini of receptor subunits is thought to play a
      significant role in modulation of N-methyl-D-aspartic acid (NMDA) receptor
      function. To investigate whether the C-terminus of the NR2A subunit is involved
      in determining the sensitivity of NMDA receptors to ethanol we compared the
      effects of ethanol in vitro on NMDA-mediated field excitatory postsynaptic
      potentials (fEPSPs) in the CA1 and dentate gyrus (DG) of adult male
      NR2A(DeltaC/DeltaC) mice lacking the C-terminus of NR2A subunit and in their
      parental strain C57Bl/6. We also tested the in vivo effects of a hypnotic dose of
      ethanol in C57Bl/6 and NR2A(DeltaC/DeltaC) mice and their F2 offspring.
      Ifenprodil (10 microM) was used to distinguish between the NR2A and NR2B
      components of NMDA fEPSPs. Ethanol (100 mM) in the presence of ifenprodil
      inhibited the CA1 NR2A-mediated component of NMDA fEPSPs two times more in
      NR2A(DeltaC/DeltaC) than in C57Bl/6. Ethanol inhibition of the CA1 NR2B-mediated
      component was five to seven times lower in NR2A(DeltaC/DeltaC) than in C57Bl/6.
      In the DG ethanol had similar effects in the two strains. In vivo administration
      of ethanol (4 g/kg) induced sedation of similar duration in both strains of mice.
      A second administration of ethanol 7 days after the initial injection revealed an
      increased ethanol sensitivity of NR2A(DeltaC/DeltaC) and F2(DeltaC/DeltaC) mice
      including a shortened time to loss of righting reflex and an increased sleep
      time. The sensitization of NR2A(DeltaC/DeltaC) mice to alcohol was not
      accompanied by an altered ethanol sensitivity of NMDA fEPSPs recorded in vitro.
      Our data are consistent with the inhibitory action of ethanol on NMDA receptors
      being mediated by a site other than the intracellular C-terminus of the NR2A
      subunit. The altered sensitivities to ethanol of both NR2A- and NR2B-mediated
      responses in the CA1 of NR2A(DeltaC/DeltaC) imply that NR2A- and NR2B subunit
      containing NMDA receptors may be linked by a common target of ethanol.

PMID- 11530238
TI  - The cytosolic antioxidant, copper/zinc superoxide dismutase, attenuates blood
      brain barrier disruption and oxidative cellular injury after photothrombotic
      cortical ischemia in mice.
AB  - Oxidative stress has been associated with the development of blood-brain barrier
      disruption and cellular injury after ischemia. The cytosolic antioxidant,
      copper/zinc superoxide dismutase, has been shown to protect against blood-brain
      barrier disruption and infarction after cerebral ischemia-reperfusion. However,
      it is not clear whether copper/zinc superoxide dismutase can protect against
      evolving ischemic lesions after thromboembolic cortical ischemia. In this study,
      the photothrombotic ischemia model, which is physiologically similar to
      thromboembolic stroke, was used to develop cortical ischemia. Blood-brain barrier
      disruption and oxidative cellular damage were investigated in transgenic mice
      that overexpress copper/zinc superoxide dismutase and in littermate wild-type
      mice after photothrombotic ischemia, which was induced by both injection of
      erythrosin B (30 mg/kg) and irradiation using a helium neon laser for 3 min. Free
      radical production, particularly superoxide, was increased in the lesioned cortex
      as early as 4 h after ischemia using hydroethidine in situ detection. The
      transgenic mice showed a prominent decrease in oxidative stress compared with the
      wild-type mice. Blood-brain barrier disruption, evidenced by quantitation of
      Evans Blue leakage, occurred 1 h after ischemia and gradually increased up to 24
      h. Compared with the wild-type mice, the transgenic mice showed less blood-brain
      barrier disruption, a decrease in oxidative DNA damage using 8-hydroxyguanosine
      immunohistochemistry, a subsequent decrease in DNA fragmentation using the in
      situ nick-end labeling technique, and decreased infarct volume after ischemia.
      From these results we suggest that superoxide anion radical is an important
      factor in blood-brain barrier disruption and oxidative cellular injury, and that
      copper/zinc superoxide dismutase could protect against the evolving infarction
      after thromboembolic cortical ischemia.

PMID- 11530240
TI  - Activation of mitogen-activated protein kinase cascade and phosphorylation of
      cytoskeletal proteins after neurone-specific activation of p21ras. I. Mitogen
      activated protein kinase cascade.
AB  - Alterations in the phosphorylation state of the microtubule-associated protein
      tau have been associated with the pathogenesis of neurofibrillary degeneration as
      well as with a neuroprotective action against apoptotic cell death. Mitogen
      activated protein kinases (MAPK) phosphorylate tau protein in vitro but the
      pathophysiological significance of this tau phosphorylation and its effects on
      neuronal viability is far from clear. Moreover, an in vivo model of activation of
      MAPK, a key candidate for in vivo tau phosphorylation, is still lacking. The aim
      of the present study and the accompanying paper was to establish an animal model
      of stimulated MAPK and to analyse the consequences on tau phosphorylation and the
      neuronal cytoskeleton. We took advantage of transgenic mice with neurone-specific
      expression of activated ras protein (p21H-ras(Val12)). The expression of the
      transgene in these animals is forced to a subset of neurones by the use of the
      synapsin I promoter. Activity of B-raf was elevated by 37%, while activity of
      MAPK (ERK1/ERK2) was increased by 25% associated with a subcellular
      redistribution from the cytoplasmic to the nuclear compartment. Kinases
      downstream of MAPK such as p90rsk and glycogen synthase kinase 3beta were only
      marginally affected. Activity of p70S6 kinase was unaltered. The present model
      might be useful to study the effects of activation of the MAPK cascade on tau
      phosphorylation and its cell biological sequelae.

PMID- 11530239
TI  - The SH2 domain-containing 5-phosphatase SHIP2 is expressed in the germinal layers
      of embryo and adult mouse brain: increased expression in N-CAM-deficient mice.
AB  - The germinative ventricular zone of embryonic brain contains neural lineage
      progenitor cells that give rise to neurons, astrocytes and oligodendrocytes. The
      ability to generate neurons persists at adulthood in restricted brain areas.
      During development, many growth factors exert their effects by interacting with
      tyrosine kinase receptors and activate the phosphatidylinositol 3-kinase and the
      Ras/MAP kinase pathways. By its ability to modulate these pathways, the recently
      identified Src homology 2 domain-containing inositol polyphosphate 5-phosphatase
      2, SHIP2, has the potential to regulate neuronal development. Using in situ
      hybridization technique with multiple synthetic oligonucleotides, we demonstrated
      that SHIP2 mRNA was highly expressed in the ventricular zone at early embryonic
      stages and subventricular zones at latter stages of brain and spinal cord and in
      the sympathetic chain. No significant expression was seen in differentiated
      fields. This restricted expression was maintained from embryonic day 11.5 to
      birth. In the periphery, large expression was detected in muscle and kidney and
      moderate expression in thyroid, pituitary gland, digestive system and bone. In
      the adult brain, SHIP2 was mainly restricted in structures containing neural stem
      cells such as the anterior subventricular zone, the rostral migratory stream and
      the olfactory tubercle. SHIP2 was also detected in the choroid plexuses and the
      granular layer of the cerebellum. The specificity of SHIP2 expression in neural
      stem cells was further demonstrated by (i) the dramatic increase in SHIP2 mRNA
      signal in neural cell adhesion molecule (N-CAM)-deficient mice, which present an
      accumulation of progenitor cells in the anterior subventricular zone and the
      rostral migratory stream, (ii) the abundant expression of 160-kDa SHIP2 by
      western blotting in proliferating neurospheres in culture and its downregulation
      in non-proliferating differentiated neurospheres. In conclusion, the close
      correlation between the pattern of SHIP2 expression in the brain and the
      proliferative and early differentiative events suggests that the phosphatase
      SHIP2 may have important roles in neural development.

PMID- 11530241
TI  - Activation of mitogen-activated protein kinase cascade and phosphorylation of
      cytoskeletal proteins after neurone-specific activation of p21ras. II.
      Cytoskeletal proteins and dendritic morphology.
AB  - In the present study, we analysed changes in the expression, subcellular
      distribution and phosphorylation state of the microtubule-associated protein tau
      and other cytoskeletal proteins after neurone-specific activation of the mitogen
      activated protein kinase (MAPK) in the CNS in vivo. We used transgenic mice with
      a neurone-specific expression of activated ras protein (p21H-ras(Val12), synapsin
      I promoter) that is associated with an augmented activity of the MAPK. Chronic
      activation of MAPK cascade influenced tau protein phosphorylation, localisation
      and dendritic morphology. While the amount of tau protein was elevated by 9%,
      phospho-epitopes detected by the monoclonal antibodies AT270, 12E8 and SMI34 were
      increased by about 21%, 40% and 59% respectively. Steady-state levels of tau mRNA
      were not affected. Thus, the increase in tau protein was most likely due to
      stabilisation of tau protein by augmented phosphorylation. While in wild-type
      animals tau protein was preferentially localised in axons, a prominent
      immunoreactivity was found in the somatodendritic compartment of transgenic mice.
      This subcellular translocation typically seen in pyramidal neurones was
      associated with an increase in the dendritic calibre by about 30% and is
      paralleled by an increase in tubulin of 19%. We were unable to obtain any
      morphological indication of neurodegenerative processes in these animals. We
      suggest that the moderate increase in tau protein and phosphorylation may be part
      of the neuroprotective mechanism. However, further studies on aged transgenic
      mice will be necessary to establish potential effects on neuronal viability.

PMID- 11530242
TI  - Differential expression of metallothioneins in the CNS of mice with experimental
      autoimmune encephalomyelitis.
AB  - Multiple sclerosis is an inflammatory, demyelinating disease of the CNS.
      Metallothioneins-I+II are antioxidant proteins induced in the CNS by
      immobilisation stress, trauma or degenerative diseases which have been postulated
      to play a neuroprotective role, while the CNS isoform metallothionein-III has
      been related to Alzheimer's disease. We have analysed metallothioneins-I-III
      expression in the CNS of mice with experimental autoimmune encephalomyelitis.
      Moreover, we have examined the putative role of interferon-gamma, a pro
      inflammatory cytokine, in the control of metallothioneins expression during
      experimental autoimmune encephalomyelitis in interferon-gamma receptor knockout
      mice with two different genetic backgrounds: 129/Sv and C57BL/6x129/Sv. Mice with
      experimental autoimmune encephalomyelitis showed a significant induction of
      metallothioneins-I+II in the spinal cord white matter, and to a lower extent in
      the brain. Interferon-gamma receptor knockout mice suffered from a more severe
      experimental autoimmune encephalomyelitis, and interestingly showed a higher
      metallothioneins-I+II induction in both white and grey matter of the spinal cord
      and in the brain. In contrast to the metallothioneins-I+II isoforms,
      metallothionein-III expression remained essentially unaltered during experimental
      autoimmune encephalomyelitis; interferon-gamma receptor knockout mice showed an
      altered metallothionein-III expression (a slight increase in the spinal cord
      white matter) only in the C57BL/6x129/Sv background. Metallothioneins-I+II
      proteins were prominent in areas of induced cellular infiltrates. Reactive
      astrocytes and activated monocytes/macrophages were the sources of
      metallothioneins-I+II proteins. From these results we suggest that
      metallothioneins-I+II but not metallothionein-III may play an important role
      during experimental autoimmune encephalomyelitis, and indicate that the pro
      inflammatory cytokine interferon-gamma is unlikely an important factor in this
      response.

PMID- 11530261
TI  - Characteristics of Korean native, Hanwoo, calves produced by transfer of in vitro
      produced embryos.
AB  - The main objectives of this investigation were to monitor the birth weight of
      calves and gestation length following artificial insemination (AI) and transfer
      of in vivo or in vitro produced Korean native, Hanwoo embryos. Embryos produced
      in vivo were recovered from uterine flushings of superovulated cows 7 days after
      AI. Those embryos produced in vitro were co-cultured with cumulus cells for 7-8
      days after in vitro fertilization. The birth weights of calves following the
      transfer of in vitro produced (IVP) embryos were heavier than calves from both of
      AI- and in vivo-derived embryo transferred calves in both sexes (29.6, 24.1 and
      25.2kg, respectively, P<0.05). The IVP calves also had a longer gestation length
      (293.9, 285.8 and 283.8 days, respectively, P<0.05).

PMID- 11530260
TI  - Some aspects of immunology of the bovine uterus related to treatments for
      endometritis.
AB  - Endometritis in breeding cattle occurs during the postpartum period, and is
      associated primarily with contamination of the reproductive tract involving
      Arcanobacter pyogenes (formerly Actinomyces pyogenes) together with Gram-negative
      anaerobes. Polymorphonuclear inflammatory cells (PMNs) contribute partly to the
      defense mechanisms against micro-organisms contaminating the vagina and uterine
      lumen, whose phagocytic activity depends on bacterial opsonisation by humoral
      antibodies; significant numbers of lymphocytes are also present. Whilst leukocyte
      numbers in the uterine lumen are relatively high during metoestrus and dioestrus
      compared to other phases of the oestrous cycle, their functional activity is
      unaffected. Humoral antibody concentrations in the reproductive tract are
      stimulated following exposure to local antigen, and the response is site
      dependent; of the several different classes of immunoglobulins, IgG predominates
      in the uterus and IgA the vagina. Only a portion of the total IgG1 found on the
      uterine lumen is synthesised locally in the endometrium, the remainder and all of
      the IgG2 is derived from the local uterine blood supply. Generally,
      concentrations of immunosuppressant proteins present in the uterine lumen
      increase under progesterone dominance, and these inhibit lymphocyte
      proliferation, making the uterus more susceptible to infection. The relationship
      between uterine susceptibility to micro-organism contamination and the luteal
      phase of the oestrous cycle is still unclear. Intrauterine infusion of
      immunomodulators such as E. coli lipopolysaccharides (LPS) or oyster glycogen, in
      healthy cows and those with endometritis, stimulates leukocytes to migrate into
      the uterine lumen. At a dosage rate of 100 microg, lipopolysaccharides are not
      absorbed by the healthy endometrium and do not alter the oestrous cycle length.
      It is unknown, whether a similar dose can be absorbed through an inflamed
      endometrium in naturally occurring cases of endometritis to cause systemic
      illness. Currently, prostaglandin F2alpha is recommended for treating
      endometritis in both cycling and non-cycling cows, but its mode of action in non
      cycling cows is not fully understood. The efficacy of endometritis treatment
      using an intrauterine infusion of an immunomodulator in cases occurring naturally
      has not been determined on a large scale.

PMID- 11530263
TI  - Effects of monensin and forage:concentrate ratio on feed intake, endocrine, and
      ovarian function in beef heifers.
AB  - The objective of this study was to determine the effects of monensin (M) and
      altered forage:concentrate ratio (F:C) on feed intake, hormonal profiles, and
      ovarian function in beef heifers. Four ruminally cannulated heifers were
      maintained in metabolism crates and fed twice daily. Diets contained 0 or 200mg
      per day M in diets of 70:30 (high forage, HF) or 30:70 (high concentrate, HC)
      F:C. Diets were limit fed to achieve isocaloric intake of calculated ME. Monensin
      supplementation had no effect on feed intake, but heifers fed HF had greater
      refusals compared with heifers fed HC (P<0.005). Serum insulin, progesterone, and
      estradiol concentrations did not differ between diets or treatments (P>0.10).
      Diet and/or treatment tended to alter the size or number of follicles on either
      or both ovaries. Monensin resulted in more waves of follicular development per
      estrous cycle with HF diets, but fewer with HC diets (P<0.07). The interovulatory
      interval, lifespan of the corpus luteum, and the size of the dominant follicle in
      the first two follicular waves were not different due to diet or treatment.
      However, the HC diet tended to produce a larger ovulatory follicle compared with
      the HF diet (HF=12.25, HC=13.5; P<0.08). We conclude that feeding monensin
      affects estradiol secretion and a higher proportion of concentrates alters
      ovarian dynamics, which could affect fertility in beef heifers.

PMID- 11530262
TI  - Expression of the bovine oestrogen receptor-beta (bERbeta) messenger ribonucleic
      acid (mRNA) during the first ovarian follicular wave and lack of change in the
      expression of bERbeta mRNA of second wave follicles after LH infusion into cows.
AB  - In a previous study, the ERbeta cDNA protein-coding region was utilised to clone
      bovine ERbeta. The objectives in this study were to examine (1) ERbeta mRNA
      expression in ovarian follicles throughout the bovine first follicular wave, and
      (2) effect of LH infusion into cows on bERbeta mRNA expression during the second
      follicular wave. In experiment 1, heifers (4-5 per time point) were
      ovariectomized at 12, 24, 36, 48, 60, 72, 84, 96, 144, or 216 h after emergence
      of the first follicular wave after oestrus. In experiment 2, saline or LH was
      pulsed hourly (computer-controlled syringe pump) into cows (n = 31; 5-6 per
      treatment) at wave emergence for 2 or 4 days: wave 1-saline (W1S), wave 2-saline
      (W2S), or wave 2-LH (25 microg/h; W2LH). Ovaries were removed on day 2 or day 4
      after wave emergence. Follicles, 2-19mm in size, were dissected, frozen, and
      stored at -80 degrees C for in situ hybridisation with two bERbeta cRNA probes.
      Expression of bERbeta mRNA was localised in granulosa cells of healthy follicles.
      In experiment 1, bERbeta mRNA expression did not change with time points of the
      wave showing no association of bERbeta mRNA expression with follicular selection
      and dominance. However, bERbeta mRNA expression decreased with increase in size
      of all follicles. Expression of bERbeta mRNA was greater in very small follicles
      (2-4 mm) than in large (> or = 9 mm) follicles. In experiment 2, expression of
      bERbeta mRNA in follicles did not differ either between W1S and W2S or between
      W2S and W2LH. In summary, bERbeta mRNA expression decreased with increasing
      follicular size. However, neither stage of the wave (selection or dominance), nor
      pulsatile infusion of LH influenced bERbeta mRNA expression.

PMID- 11530264
TI  - Pre-parturition profile of steroids and prostaglandin in cows with or without
      foetal membrane retention.
AB  - Retained foetal membranes in cattle is one of the most common complications
      associated to the reduction in milk yield and impaired fertility in dairy cattle.
      In order to determine some endocrine mechanisms controlling parturition and
      delivery of foetal membranes, plasma concentrations of steroids and prostanoids
      were determined in 20 healthy Holstein cows. Samples were taken within the
      interval of 5 days pre-parturition to 12h after calving. Progesterone (P4) levels
      were similar in cows with (PR) and without (NPR) placental retention. While the
      estradiol-17beta (E2) peak at parturition was lower in PR than in NPR cows,
      cortisol levels were greater in PR cows 12 and 24h pre-parturition. The
      Prostaglandin F2alpha metabolite (PGFM) levels were higher at parturition in NPR
      compared with the PR group, but 12h later, these levels in the PR group increased
      so that concentrations were greater as compared with NPR cows. The Prostaglandin
      E2 metabolite (PGEM), 24, 48 and 72 h pre-parturition, were higher in PR cows.
      However, the PGFM:PGEM ratio was greater in cows up NPR at all time when
      included, indicating the importance of higher levels of Prostaglandin F2alpha
      (PGF2alpha) than Prostaglandin E2 (PGE2) for normal placental delivery. In
      conclusion, placental retention was related to both estrogen and PGF2alpha
      deficiency, which may be a consequence of metabolic stress leading to PGE2 and
      maternal cortisol synthesis before parturition.

PMID- 11530265
TI  - Concentrations of steroids and expression of messenger RNA for steroidogenic
      enzymes and gonadotropin receptors in bovine ovarian follicles of first and
      second waves and changes in second wave follicles after pulsatile LH infusion.
AB  - The objectives were to compare expression of mRNA for cytochrome P450 cholesterol
      side-chain cleavage (P450scc), cytochrome P450 17alpha-hydroxylase (P450c17),
      cytochrome P450 aromatase (P450arom), 3beta-hydroxysteroid dehydrogenase
      Delta(4), Delta(5) isomerase (3beta-HSD), FSH receptor (FSHr) and LH receptor
      (LHr) in bovine ovarian follicles of the first and second waves of the bovine
      oestrous cycle and to determine if LH infusion changes growth, steroidogenesis
      and gene expression in second wave follicles. Transrectal ultrasonography was
      used to examine follicular size changes during the oestrous cycle in non
      lactating Holstein cows (n=31). Saline or purified bovine LH was infused
      intravenously into cows at emergence of follicular waves for 2 or 4 days using a
      computer-controlled syringe pump (n=5-6 per treatment). Treatments were: wave 1,
      saline (W1S); wave 2, saline (W2S) or LH (25 microg/h; W2LH). During infusion,
      blood samples were collected at 12min intervals for 8h via i.v. catheters for
      measurement of serum LH concentrations. Ovaries were removed from cows on days 2
      or 4 after emergence of follicular waves. Follicles were frozen and stored at -80
      degrees C. Follicular fluid (FF, 50 microl) was collected for determination of
      progesterone (P4), oestradiol-17beta (E2) and androstenedione (A4)
      concentrations. Frozen sections (14 microm) were used for in situ hybridization
      to measure expression of mRNA (% pixel intensity) for P450scc, P450c17, P450arom,
      3beta-HSD, FSHr, and LHr. LH infusion resulted in a serum LH pattern (high
      frequency) similar to the early luteal phase. There were no significant
      differences in size of follicles among the three treatment groups. Follicular
      fluid concentrations of E2 and A4 in W2S were lower than those of W1S on day 2 of
      a follicular wave. LH infusion into cows during the midluteal phase increased
      follicular fluid E2 and A4 concentrations in second wave follicles on day 2 of a
      follicular wave (W2LH) compared to those of W2S. The increase in follicular fluid
      E2 on day 2 in wave 2 follicles after LH infusion occurred possibly through an
      increase in mRNA expression of P450c17 and 3beta-HSD. In conclusion, follicular
      fluid concentrations of E2 and A4 were lower in W2S than in W1S and E2 and A4
      concentrations were restored by infusion of LH in W2LH with an increase in mRNA
      expression of P450c17 and 3beta-HSD.

PMID- 11530266
TI  - The effect of level of feed intake on progesterone clearance rate by measuring
      faecal progesterone metabolites in grazing dairy cows.
AB  - The objective of the present study was to determine the effect of level of feed
      intake of pasture on P4 clearance rates in dairy cows. Twelve non-lactating
      Holstein-Friesian cows aged 4-9 years were randomly allocated to a restricted or
      ad libitum group. The ad libitum group had unrestricted access to irrigated
      pasture, whereas the restricted group had access for only 2h per day. Each animal
      was drenched orally twice daily with a chromic oxide capsule to allow daily feed
      intake to be estimated from faecal output (FO). Endogenous progesterone (P4)
      production was eliminated by subcutanously implanting a capsule containing 6 mg
      of a potent GnRH-agonist (deslorelin) into the ear of each animal 3 weeks before
      inserting a CIDR device containing 1.9 g P4 into the vagina. Two luteolytic
      PGF2alpha were given 10 days later. Each device was removed after 11 days and
      residual P4 measured. Daily plasma samples were assayed for P4. Faecal samples
      were also taken daily and assayed for pregnanes (FP4M) containing a 20-oxo-, a
      20alpha- or a 20beta-OH group with EIAs. The average daily dry matter (DM) intake
      of pasture was higher for cows in the ad libitum group (15.9 versus 6.3 kg DM,
      P=0.001). Their plasma P4 concentrations were lower (1.08 versus 1.71 ng/ml,
      P=0.05), even though the average residual P4 content of the used CIDR devices was
      not affected by feed intake (1.20 versus 1.25 g, P>0.05). The concentrations of
      FP4M were not affected by level of feed intake (20-oxo-: 3.3 versus 1.7, 20alpha
      : 3.5 versus 3.7, 20beta-: 2.1 versus 3.2 microg/g DM). Daily excretion rates of
      20-oxo- and 20alpha- were higher in ad libitum cows (20-oxo-: 17.8 versus 4.3mg
      per day, P=0.05; 20alpha-: 18.2 versus 8.9 mg per day, P=0.001), but daily yield
      of faecal 20beta- was not affected by feed intake (11.9 versus 8.6 mg per day,
      P=0.5). These results show that there was a negative relationship between feed
      intake and plasma P4 concentrations in these CIDR-treated GnRH-downregulated
      Holstein cows. Concentrations of FP4M were not affected by level of feed intake
      or FO, but daily excretion rate of FP4M was associated with the volume of faeces.

PMID- 11530267
TI  - The effects of pokeweed mitogen (PWM) and phytohemagglutinin (PHA) on bovine
      oocyte maturation and embryo development in vitro.
AB  - The effects of two commonly used cell culture mitogens, pokeweed (PWM) and
      phytohemagglutinin (PHA) on bovine oocyte maturation in vitro (IVM) and
      preimplantation embryo development in vitro were evaluated by randomized complete
      block experimental design with three treatments. Effects were measured by
      quantifying subsequent embryo development. Oocyte maturation was adversely
      affected by PWM-containing medium as indicated by a decrease in cleavage rate and
      subsequent embryo development to morula and blastocyst stages. Embryo
      developmental competence was also adversely affected by PWM. Development in PHA
      containing medium was significantly better (P<0.05) than in the PWM treatment,
      although there was no difference (P>0.05) when compared to Control. We conclude
      that there are no beneficial effects in adding mitogenic agents to culture medium
      to enhance in vitro embryo production and development.

PMID- 11530268
TI  - The use of GnRH or estradiol to facilitate fixed-time insemination in an MGA
      based synchronization regimen in beef cattle.
AB  - Two experiments were conducted to compare pregnancy rates when GnRH or estradiol
      were given to synchronize ovarian follicular wave emergence and ovulation in an
      MGA-based estrus synchronization program. Crossbred beef cattle were fed
      melengestrol acetate (MGA, 0.5 mg per day) for 7 days (designated days 0-6,
      without regard to stage of the estrous cycle) and given cloprostenol (PGF; 500
      microg intramuscular (im)) on day 7. In Experiment 1, lactating beef cows (n=140)
      and pubertal heifers (n=40) were randomly allocated to three groups to receive
      100 microg gonadorelin (GnRH), 5 mg estradiol-17beta and 100 mg progesterone
      (E+P) in canola oil or no treatment (control) on day 0. All cattle were observed
      for estrus every 12 h from 36 to 96 h after PGF. Cattle in the GnRH group that
      were detected in estrus 36 or 48 h after PGF were inseminated 12 h later; the
      remainder were given 100 microg GnRH im 72 h after PGF and concurrently
      inseminated. Cattle in the E+P group were randomly assigned to receive either 0.5
      or 1.0 mg estradiol benzoate (EB) in 2 ml canola oil im 24 h after PGF and were
      inseminated 30 h later. Cattle in the control group were inseminated 12 h after
      the first detection of estrus; if not in estrus by 72 h after PGF, they were
      given 100 microg GnRH im and concurrently inseminated. In the absence of
      significant differences, all data for heifers and for cows were combined and the
      0.5 and 1.0 mg EB groups were combined into a single estradiol group. Estrus
      rates were 57.6, 57.4 and 60.0% for the GnRH, E+P and control groups,
      respectively (P=0.95). The mean (+/-S.D.) interval from PGF treatment to estrus
      was shorter (P<0.001) and less variable (P<0.001) in the E+P group (49.0+/-6.1 h)
      than in either the GnRH (64.2+/-15.9 h) or control (66.3+/-13.3 h) groups.
      Overall pregnancy rates were higher (P<0.005) in the GnRH (57.6%) and E+P (55.7%)
      groups than in the control group (30.0%) as were pregnancy rates to fixed-time AI
      (47.5, 55.7 and 28.3%, respectively). In Experiment 2, 122 crossbred beef heifers
      were given either 100 microg GnRH or 2 mg EB and 50 mg progesterone in oil on day
      0 and subsequently received either 100 microg GnRH 36 h after PGF and inseminated
      14 h later or 1 mg EB im 24 h after PGF and inseminated 28 h later in a 2 x 2
      factorial design. Pregnancy rates were not significantly different among groups
      (41.9, 32.2, 33.3 and 36.7% in GnRH/GnRH, GnRH/EB, EB/GnRH and EB/EB groups,
      respectively). In conclusion, GnRH or estradiol given to synchronize ovarian
      follicular wave emergence and ovulation in an MGA-based synchronization regimen
      resulted in acceptable pregnancy rates to fixed-time insemination.

PMID- 11530269
TI  - Fertilizing characteristics of bovine sperm with flattened or indented acrosomes.
AB  - Frozen semen from a control bull (C: 89% morphologically normal sperm) and two
      bulls with acrosomal defects (K1: 92% flattened acrosomes; K2: 82% indented
      acrosomes) were used to investigate the fertilizing ability of bull sperm with
      flattened or indented acrosomes. In experiment 1, frozen-thawed sperm were
      evaluated for acrosomal integrity with fluorescent microscopy. In experiment 2,
      proteolytic activity of the acrosomal contents of sperm was evaluated through a
      gelatin digestion assay. In experiment 3, an IVF test system was used to
      determine the ability of sperm with flattened or indented acrosomes to bind to
      bovine oocytes and penetrate the zona pellucida. In experiment 4, IVM zona-free
      bovine oocytes (ZFO) were fertilized and examined to evaluate sperm chromatin
      decondensation. In experiment 1, bulls K1 and K2 had a lower proportion of sperm
      with intact acrosomes (0 and 13.6 +/- 4.5%, respectively) than bull C (30.2 +/-
      5.6%) after 2h of incubation. In experiment 2, the proportion of sperm with
      proteolytic activity, as indicated by gelatin digestion around sperm heads, did
      not differ among bulls (C: 55%, n=410; K1: 43%, n=426; K2: 48%, n=324). In
      experiment 3, a lower proportion of sperm with flattened (K1) or indented
      acrosomes (K2) bound to oocytes than sperm from the control bull, C. The
      percentage of zona penetrated (55%, n=20; 13%, n=23; 4%, n=25) and the mean (+/-
      S.E.M.) number of sperm penetrating these zona pellucida (19.7 +/- 2.5; 6.9 +/-
      1.0; and 2.6 +/- 0.5) was higher (P<0.05) for bull C than for bulls K1 or K2,
      respectively. In experiment 4, the percentage of ZFO penetrated (95%, n=20; 52%,
      n=30; 30%, n=33) and the mean (+/- S.E.M.) number of sperm with chromatin
      decondensation (7.8 +/- 1.6; 0.8 +/- 0.2; and 0.3 +/- 0.1) were also higher
      (P<0.05) for the control bull, C than for bulls K1 or K2, respectively. Results
      suggest that although sperm with the flattened or indented acrosomes had a
      tendency to undergo spontaneous acrosome reaction on incubation after thawing,
      the proteolytic activity of the acrosomal contents appeared to be normal. Sperm
      with the flattened or indented acrosomes also appeared to have a reduced ability
      to fuse with oolemma as demonstrated by confocal microscopy. This would impair
      the ability to penetrate ooplasm and undergo sperm chromatin decondensation.

PMID- 11530270
TI  - Effect of oestradiol treatment during GnRH-induced ovulation on subsequent
      PGF2alpha release and luteal life span in anoestrous ewes.
AB  - In sheep, induction of ovulation during anoestrus is accompanied by a high
      incidence of short luteal phases, though pre-treatment with progesterone can
      overcome this problem. We have investigated the effects of supplementing
      oestradiol during GnRH-induced ovulation on subsequent PGF2alpha release and
      luteal life span. Thirty anoestrous crossbred ewes received 250 ng GnRH i.v. at 2
      h intervals for 48 h to induce ovulation either alone (group 1; n=10) or in
      association with either an i.m. injection of 20 mg progesterone 3 days earlier
      (group 2; n=10) or 3 i.m. injections of 10 microg oestradiol at 8 h intervals on
      the second day of GnRH treatment (group 3; n=10). Laparoscopy, performed 3 days
      following GnRH to confirm ovulation and 8 days later, coupled with plasma
      progesterone analysis were used to determine luteal life span. On day 4 following
      GnRH, plasma samples were collected at 20 min intervals for 8 h to monitor
      PGF2alpha release. One ewe from group 1 failed to ovulate and was excluded from
      further analysis. All groups showed an increase (P<0.01) in plasma oestradiol
      during GnRH treatment, with group 3 showing a marked (P<0.001) increase over that
      seen in the other two groups. In group 1 there were 1.4+/-0.2 PGF2alpha
      episodes/ewe/8 h. In group 2, pre-treatment with progesterone caused the complete
      inhibition of PGF2alpha episodes (0 episodes/ewe/8 h) while in group 3, treatment
      with oestradiol resulted in a significant reduction (0.3+/-0.1 episodes/ewe/8 h)
      compared with group 1 (P<0.01). In group 1, 9/9 ewes exhibited short cycles
      compared with 2/10 ewes in group 2 (P<0.01). In group 3 the proportion of ewes
      showing short cycles 7/10 ewes was not significantly different from the other
      groups. While treatment with oestradiol caused a significant attenuation of
      PGF2alpha release, this was associated with only a partial reduction in the
      incidence of short cycles.

PMID- 11530271
TI  - Effects of Leucaena pallida and Sesbania sesban supplementation on testicular
      histology of tropical sheep and goats.
AB  - Thirty Ethiopian highland rams with an average body weight of 23.7kg (S.D.=1.23)
      and age of 18 months and 25 East African bucks with an average body weight of
      18.6kg (S.D.=2.06) and age of 14 months were used to study the long term effects
      of supplementation with the leaves of Leucaena pallida and Sesbania sesban on
      testicular histology. Within species, animals were blocked based on body weight
      and scrotal circumference and randomly assigned, within blocks, to five
      nutritional treatment groups in a complete randomised block design. All animals
      were provided with unchopped teff (Eragrostis tef) straw ad libitum and were
      supplemented with either 150g of wheat bran (control), leucaena (200 or 400g) or
      sesbania (200 or 400g) leaves for a period of 6 months. At the end of the
      experimental period, all animals were surgically castrated and testicular samples
      were collected and prepared for histopathological examination. In sheep 200g S.
      sesban induced relatively more necrosis of the seminiferous tubules than 200g L.
      pallida, but with similar degree of tubular degeneration. However, lesions in
      testis of goats fed on 200g S. sesban and 200g L. pallida did not differ. The
      effect of 400g S. sesban and 400g L. pallida in sheep indicated that the former
      hardly induced lesions except depressive effect on spermatogenesis. Similar
      results were observed in goats. About 400g S. sesban induced milder lesions in
      sheep and goats than were 200g S. sesban. The lesions were compared and discussed
      in relation to the phytochemical composition of the supplementary feeds.

PMID- 11530272
TI  - Repeat breeding and subsequent reproductive performance in Swedish Landrace and
      Swedish Yorkshire sows.
AB  - The objective of the present study was to analyse the association between repeat
      breeding (RB) in gilts/sows and their subsequent reproductive performance as well
      as the impact of interactions between repeat breeding and factors like parity
      number, boar breed, season and mating type (MT) on subsequent reproductive
      performance in Swedish Landrace (L) and Swedish Yorkshire (Y) sows. Data analysed
      included 7040 sows (3654 L and 3386 Y), farrowing during January 1994 until
      December 1999 in 11 L and 8 Y nucleus herds. The study was assigned as a cohort
      design and the aim was to study gilts/sows from their first mating as gilts until
      mating after third parity. Analysis of variance was applied to continuous data
      and logistic regression was applied to categorical data. Percentages of litters
      as a result of repeat breeding in sow parities 1-3 were 6.1, 12.0 and 6.3% for L
      sows and 6.7, 13.1 and 7.4% for Y sows. For parity 3, the incidence of litters
      resulting from repeat breeding was significantly higher (P<0.001) in Y than in L
      sows. The proportion of irregular return to oestrus (>24 days after first mating)
      was higher (P<0.01) in primiparous sows than in multiparous sows (69% versus
      61%). On average, litters resulting from repeat breeding were larger (P<0.001)
      than litters resulting from non-repeat breeding (NR) (about 0.5 piglets per
      litter) in both L and Y sows. For Y sows, if the previous litter was a result of
      repeat breeding, the subsequent reproductive cycle had 2.7% higher RR (P<0.05)
      and 2.4% lower FR (N.S.) compared with sows that were not repeat bred. The same
      trend was found in L sows (1.4% higher RR and 1.3% lower FR) but the differences
      were not significant. Among the sows removed from the herds, about 24% of L and
      28% of Y were culled due to reproductive problems (gilts not included). In
      addition, a number of sows from these nucleus herds were also culled due to low
      breeding value and poor conformation.

PMID- 11530273
TI  - Volumetric analysis of the pre-frontal regions: findings in aging and
      schizophrenia.
AB  - Frontal lobe dysfunction is thought to be involved in schizophrenia and age
      associated cognitive decline. Frontal lobe volume changes have been investigated
      in these conditions using MRI, but results have been inconsistent. Few volumetric
      MRI protocols exist that divide the pre-frontal cortex into its sub-regions. In
      the present article, we describe a new method, which allows assessment of the
      superior, middle and inferior frontal gyrus, as well as the orbitofrontal and
      cingulate regions. The method uses multiple planes to help guide the anatomical
      decisions and combines this with a geometric approach utilizing readily apparent
      anatomical landmarks. Using this protocol, the frontal lobe volumes in young
      healthy subjects were contrasted with those of young schizophrenic patients and
      elderly healthy subjects (nine male subjects per group). The results showed that
      the method could be reproduced with high reliability (r(icc)> or =0.88-0.99).
      Schizophrenic as well as old subjects had specific significant reductions in the
      superior frontal gyrus and orbitofrontal regions compared with the young group.
      However, old and schizophrenic subjects did not differ from each another. No
      volume differences were observed in the other three regions assessed. Whether or
      not these volume reductions reflect a common pathological process remains to be
      investigated in future studies.

PMID- 11530274
TI  - Amygdala-hippocampal volume and verbal memory in first-degree relatives of
      schizophrenic patients.
AB  - Verbal memory deficits have been related to reduced volume of medial temporal
      structures in several neurological and psychiatric populations, including
      schizophrenic patients. Impairments in verbal memory have been proposed to be a
      marker of risk for schizophrenia. Recently, relatives of schizophrenic patients
      have been reported to have reduced volume of the amygdala-hippocampal complex. In
      this study, we evaluate the possibility that amygdala-hippocampal volume
      reductions may constitute one neural substrate of verbal memory deficits in first
      degree relatives. Subjects were 20 healthy first-degree relatives of
      schizophrenic patients and 14 demographically similar controls. Verbal memory was
      assessed with the Logical Memory Test. Subjects were scanned with high-resolution
      MRI and the images were transformed into Talairach space. Volumes of interest
      were amygdala-anterior hippocampus and posterior hippocampus. Relatives of
      schizophrenic patients had intact immediate verbal memory but significantly
      poorer delayed verbal memory than controls. Relatives also had significantly
      reduced amygdala-anterior hippocampus volumes. Across all subjects, delayed
      verbal memory was significantly correlated with amygdala-anterior hippocampus
      volume. The magnitude of the correlation did not differ between the groups. These
      data provide an empirical link between memory performance and volumetric
      abnormalities in the amygdala-hippocampal complex in the relatives of
      schizophrenic patients.

PMID- 11530275
TI  - Double-blind olanzapine vs. haloperidol D2 dopamine receptor blockade in
      schizophrenic patients: a baseline-endpoint.
AB  - The aim of this study was to compare in vivo striatal D2 dopamine receptor
      occupancy induced by olanzapine and haloperidol in schizophrenic patients using a
      baseline-endpoint [(123)I]IBZM single photon computed emission tomography (SPECT)
      design. The relationships of striatal D2 receptor occupancy with clinical
      efficacy and extrapyramidal symptoms (EPS) were also assessed. Twenty-seven
      inpatients with schizophrenia or schizophreniform disorder were included in a 4
      week prospective, randomized, double-blind, parallel and comparative clinical
      trial. Thirteen patients were treated with haloperidol (10 mg/day) and 14 with
      olanzapine (10 mg/day). Ratings of clinical status and EPS were obtained weekly.
      The percentage of D2 receptor occupancy was estimated by using basal ganglia
      (striatum)/frontal cortex IBZM uptake ratios obtained from each patient before
      and after 4 weeks of maintained antipsychotic treatment. Olanzapine led to a mean
      striatal D2 receptor occupancy of 49% (range 28-69%), which was significantly
      lower than that induced by haloperidol (mean 64%, range 46-90%). The baseline
      endpoint SPECT design used in this study revealed lower antipsychotic D2
      occupancy percentage values than those reported in the literature, using other
      approaches. The degree of striatal D2 receptor occupancy correlated to the EPS,
      which predominantly appeared in patients on haloperidol. No relationship was
      found between the striatal D2 receptor occupancy and clinical improvement.
      Olanzapine induced a lower striatal D2 occupancy than haloperidol. This low
      striatal D2 occupancy, together with the lower incidence of EPS in olanzapine
      treated patients, contributed to confirm the atypical behavior of this new
      antipsychotic drug. Nevertheless, conclusions based on SPECT-estimated
      percentages of antipsychotic D2 occupancy should be cautious, since the SPECT
      design could influence the results. In this regard, SPECT studies including
      baseline and endpoint examinations should be encouraged.

PMID- 11530276
TI  - In-vivo analysis of the human planum temporale (PT): does the definition of PT
      borders influence the results with regard to cerebral asymmetry and correlation
      with handedness?
AB  - The aim of our study was to examine whether the degree of planum temporale (PT)
      asymmetry and the possible correlation of morphological PT asymmetries with
      handedness are influenced by the definition of PT borders. For this reason, we
      applied three different anatomical PT definitions formerly used in the
      literature. The PT total (with the end of the Sylvian fissure (SF) as its
      posterior border) was separated into anterior and posterior regions. The border
      between anterior and posterior PT was set according to the following definitions:
      at the end of Heschl's gyrus (1st definition); at the start of the ascending SF
      ramus according to the 'knife-cut' method (2nd definition); and at the
      bifurcation of the SF (3rd definition). Thirty right-handed healthy men were
      recruited. MRI data sets analyzed with the software program BRAINS were used for
      in vivo PT volumetry. The Edinburgh Handedness Inventory (EHI) and the Hand
      Dominance Test were used to determine the degree of handedness. In summary, we
      detected that the type and the degree of asymmetry between left and right PT were
      strongly dependent on the definition used for PT borders: a left>right asymmetry
      was found in all PT regions, except a right>left asymmetry of the anterior PT
      according to our 1st PT definition (lateral to Heschl's gyrus) and a symmetry of
      the posterior PT according to our 3rd PT definition (posterior to SF
      bifurcation). In addition, a significant correlation was found between the degree
      of handedness measured by the EHI and the right posterior PT (3rd definition). We
      conclude that the influence of the definition of PT borders on the investigated
      variables may explain some of the variances between former investigations on PT
      asymmetry and handedness. The possible implications of the correlation between
      handedness and the extension of the right parietal PT are discussed and have to
      be elucidated by further studies.

PMID- 11530277
TI  - No evidence for dependence of early cortical auditory processing on dopamine D(2)
      receptor modulation: a whole-head magnetoencephalographic study.
AB  - Magnetoencephalography (MEG) was used to determine the effect of neuroleptic
      challenge on brain responses in healthy subjects. In a double-blind, randomized,
      placebo-controlled, cross-over design study, the dopamine D(2) receptor
      antagonist haloperidol (2 mg) was given orally to 12 healthy volunteers. The
      middle-latency auditory evoked magnetic fields (MAEF) were recorded 3 h after
      administration of haloperidol or placebo with a whole-head 122-channel MEG.
      Haloperidol did not significantly affect MAEF responses. The dipole moments and
      source locations of the responses were not significantly influenced by
      haloperidol. These results suggest that dopamine D(2) receptors are not involved
      in the early phases of auditory cortical processing.

PMID- 11530278
TI  - Reflections on sterol sidechain cleavage process catalyzed by cytochrome
      P450(scc).
AB  - The essay examines the evidence upon which the presently accepted version of the
      mechanism of the cytochrome P450(scc)-catalyzed-cleavage of the sidechain of
      cholesterol is based. This analysis indicates that the generally held view of the
      process (two consecutive hydroxylations, followed by cleavage of the resulting
      glycol) most likely does not describe the true mechanism. The available evidence
      can not be used to support this traditional notion. Two alternative hypotheses
      are proposed.

PMID- 11530279
TI  - Codon 325 sequence polymorphism of the estrogen receptor alpha gene and bone
      mineral density in postmenopausal women.
AB  - Estrogen receptor alpha (ER alpha) encoding gene is one of the candidate genes to
      be involved in the development of osteoporosis. Until now correlation between
      three ER gene polymorphisms (identified with PvuII, XbaI and BstUI) and bone
      mineral density (BMD) have been investigated. The results of these studies are
      contradictory. Thus the aim of our work was to search for new, yet unknown, and
      probably more informative polymorphism(s) of the ER alpha gene. For detection of
      mutations the whole coding region of the ER alpha gene was screened
      systematically. In a group of 85 late postmenopausal women all of the eight exons
      were amplified by polymerase chain reaction (PCR) and fragments were further
      analyzed by single-stranded conformation polymorphism (SSCP) analysis. Mutations
      were confirmed by direct DNA sequencing. In the whole coding region of the ER
      alpha gene two silent mutations in codon 87 and 325, respectively, were found.
      The silent mutation in codon 85 of exon 1 (GCG-->GCC; A87A) was described
      previously, as BstUI polymorphism. On the other side, the silent mutation in
      codon 325 (CCC-->CCG; P325P), located in exon 4, has not been analyzed so far in
      correlation with BMD. According to the distribution of genotypes
      CC:CG:GG=49.4:41.2:9.4, we can affirm the existence of genetic polymorphism in
      codon 325 in our population of late postmenopausal women. The mean femoral neck
      BMD, but not the lumbar spine BMD, was significantly lower (P=0.029) in the
      homozygous GG-women with CCG/CCG codon 325 as compared to the homozygous CC-women
      with the normal codon CCC/CCC. Our results suggest that codon 325 sequence
      polymorphism of the ER alpha gene might be one of the factors associated with low
      femoral neck BMD.

PMID- 11530280
TI  - Paradoxical effect of estradiol: it can block its own bioformation in human
      breast cancer cells.
AB  - The great majority of breast cancers are in their early stage hormone-dependent
      and it is well accepted that estradiol (E(2)) plays an important role in the
      genesis and evolution of this tumor. Human breast cancer tissues contain all the
      enzymes: estrone sulfatase, 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD),
      aromatase, involved in the last steps of E(2) bioformation in this tissue.
      Quantitative data show that the 'sulfatase pathway', which transforms estrogen
      sulfates into the bioactive unconjugated E(2), is 100-500 times higher than the
      'aromatase pathway' which converts androgens into estrogens. In this paper we
      explore the effect of E(2) on the sulfatase activity using two hormone-dependent
      human breast cancer cells: MCF-7 and T-47D. The action of E(2) on the sulfatase
      activity was evaluated by the conversion of estrone sulfate (E(1)S) into E(2).
      The cells were incubated in Minimal Essential Medium (MEM) containing 5% steroid
      depleted fetal calf serum and incubated with physiological concentrations of
      [(3)H]E(1)S (5 x 10(-9) M) alone (control) or in the presence of E(2) (5 x 10(
      10) to 5 x 10(-5) M) for 24 h at 37 degrees C. It was found that E(2) is a potent
      inhibitory agent of the estrone sulfatase activity in both cell lines. A low
      concentration of E(2): 5 x 10(-9) M decreases the sulfatase activity by 67% in
      MCF-7 cells and 57% in T-47D cells. More than 80% of the decrease in the
      formation of E(2) was obtained with the dose of 5 x 10(-7) M in both cell lines.
      It is concluded that this paradoxical effect of E(2) adds a new biological
      response of this hormone and could be related to estrogen replacement therapy in
      which it was observed to have either no effect or to decrease breast cancer
      mortality in postmenopausal women. Preliminary results are indicated in the
      Proceedings of the 14th International Symposium of the Journal of Steroid
      Biochemistry & Molecular Biology (Quebec, Canada, 24-27 June 2000) [J. Steroid
      Biochem. Molec. Biol. 76 (2001) 95-104](1) and presented at the 83rd Annual
      Meeting of the Endocrine Society (Denver, USA, 20-23 June 2001 (abstract no. P2
      615).

PMID- 11530281
TI  - Differential activation of wild-type and variant forms of estrogen receptor alpha
      by synthetic and natural estrogenic compounds using a promoter containing three
      estrogen-responsive elements.
AB  - Structure-dependent estrogen receptor alpha (ER alpha) agonist and antagonist
      activities of synthetic and natural estrogenic compounds were investigated in
      human HepG2, MDA-MB-231 and U2 cancer cell lines. Compounds used in this study
      include 4'-hydroxytamoxifen, ICI 182,780, bisphenol-A (BPA), 2',4',6'-trichloro-4
      biphenylol (3Cl-PCB-OH), 2',3',4',5'-tetrachloro-4-biphenylol (4Cl-PCB-OH), p-t
      octylphenol, p-nonylphenol, naringenin, kepone, resveratrol, and 2,2-bis(p
      hydroxyphenyl)-1,1,1-trichloroethane (HPTE). Cells were transfected with a
      construct (pERE(3)) containing three tandem estrogen responsive elements (EREs)
      and either wild-type estrogen receptor alpha (ER-wt) or variants expressing
      activation function-1 (ER-AF1) or AF-2 (ER-AF2). The ER agonist activities of the
      synthetic mono and dihydroxy aromatic compounds are comparable in all three-cell
      lines, whereas the activities of naringenin, kepone and resveratrol are dependent
      on cell context and expression of wild-type or variant forms of ER alpha. In
      contrast, the ER antagonist activities for these compounds were highly complex
      and, with the exception of 3Cl-PCB-OH, all compounds inhibited E2-induced wild
      type or variant ER action. Results of this in vitro study suggest that the
      estrogenic and antiestrogenic activity of structurally diverse synthetic and
      natural estrogenic compounds is complex, and this is consistent with published
      data that often give contradictory results for these compounds.

PMID- 11530282
TI  - The multiple untranslated first exons system of the human estrogen receptor beta
      (ER beta) gene.
AB  - In order to investigate the regulatory mechanism of the expression of the human
      estrogen receptor beta (ER beta) gene, we have analyzed the structure of the 5'
      untranslated region of the ER beta mRNA in the normal uterine endometrium and
      liver using the 5'-rapid amplification of the cDNA ends method. The sequence
      analysis revealed the presence of the two isoforms of the ER beta mRNA containing
      the distinct 5'-untranslated regions. The genomic analysis revealed that the two
      isoforms of the message originated from the two distinct untranslated first
      exons, termed the exon 0K and exon 0N, which were spliced to the exon 1. We
      termed the two isoforms of the message the ER beta mRNA (0K-1) and ER beta mRNA
      (0N-1). We further analyzed the distribution of the ER beta mRNA (0K-1) and ER
      beta mRNA (0N-1) in the ejaculated spermatozoa, liver, uterine endometrium and
      myometrium, and peripheral leukocytes using the reverse transcription-polymerase
      chain reaction. The distributions of the two mRNA isoforms were different from
      each other. From these results, it is indicated for the first time that the
      expression of the human estrogen receptor beta (ER beta) gene is regulated, at
      least in part, by the multiple untranslated first exons and promoters system.

PMID- 11530283
TI  - Estrogen receptor alpha mediated induction of the transforming growth factor
      alpha gene by estradiol and 4-hydroxytamoxifen in MDA-MB-231 breast cancer cells.
AB  - The selective estrogen receptor modulator, 4-hydroxytamoxifen (4-OHT) is a full
      agonist at the transforming growth factor (TGF) alpha gene in ER negative breast
      cancer cells stably transfected with ER alpha cDNA (Levenson et al., Br. J.
      Cancer 77 (1998) 1812-1819). E(2) and 4-OHT increase TGF alpha mRNA and protein
      in a concentration dependent manner. The responses to E(2) and 4-OHT are blocked
      by the pure antiestrogen ICI 182,780, which does not induce TGF alpha.
      Transfected MDA-MB-231 cells contain functional ER alpha but no ER beta function
      was detected. Neo transfected cells that did not express ER alpha or cells stably
      transfected with the DNA binding domain mutant C202R/E203V which prevents gene
      activation did not induce TGF alpha mRNA after either E(2) or 4-OHT treatment. An
      examination of the time course for either 10 nM E(2) or 1 microM 4-OHT for MDA-MB
      231 cells stably transfected with cDNA for ER alpha showed increases in TGF alpha
      mRNA within 2 or 3 h respectively. Cells pretreated with cycloheximide (1
      microg/ml) showed induced TGF alpha mRNA in response to E(2) or 4-OHT but TGF
      alpha mRNA induction was blocked by actinomycin D (1 microg/ml). We conclude that
      both E(2) and 4-OHT induce TGF alpha by direct interaction of ER alpha with DNA
      and that ER beta is not involved in the estrogen-like response to 4-OHT in the
      MDA-MB-231 cells.

PMID- 11530284
TI  - Neuroactive steroids, their precursors and polar conjugates during parturition
      and postpartum in maternal blood: 2. Time profiles of pregnanolone isomers.
AB  - Time profiles of the pregnanolone isomers epipregnanolone (3 beta-hydroxy-5 beta
      pregnan-20-one), allopregnanolone (3 alpha-hydroxy-5 alpha-pregnan-20-one),
      pregnanolone (3 alpha-hydroxy-5 beta-pregnan-20-one), and isopregnanolone (3 beta
      hydroxy-5 alpha-pregnan-20-one) were measured around parturition and in the
      postpartum period in the serum of 13 and three women with subarachnoidal and
      epidural analgesia, respectively. In addition, the levels of polar conjugates of
      all pregnanolone isomers were followed during parturition. GC/MS analysis was
      used for the measurement of steroid levels. Changes in concentrations of free
      steroids exhibited a similar pattern, with a fall primarily within the first hour
      after delivery. The decrease in conjugated steroids was shifted to the interval
      within the first hour and first day after delivery, and the changes were more
      pronounced. The time profile of the conjugated/free steroid ratio exhibited a
      significant decrease within the first hour and the first day after delivery in
      all of the isomers investigated. A decrease was also observed in the ratio of 3
      alpha/3 beta-isomers and 5 alpha/5 beta-isomers around parturition. The possible
      physiological consequences of the findings are indicated.

PMID- 11530285
TI  - Effects of the heterogeneous nuclear ribonucleoprotein U (hnRNP U/SAF-A) on
      glucocorticoid-dependent transcription in vivo.
AB  - The glucocorticoid receptor (GR) is a ligand dependent transcription factor,
      which regulates the transcription of multiple hormone-dependent genes. The
      transcriptional regulation by GR takes place by interaction of GR with the basal
      transcription machinery and by recruiting glucocorticoid receptor interacting
      proteins (GRIPs). Previously we identified hnRNP U/SAF-A as a factor interfering
      with GR-dependent transcription by repressing glucocorticoid induced activation.
      To gain insight into the mechanisms that govern this interference, we have now
      investigated the transcription of GR-dependent reporter genes in Ltk(-) cells
      transiently transfected with a variety of hnRNP U constructs. We demonstrate that
      a hnRNP U construct lacking the GR-binding domain acts as a dominant negative
      factor that now enhances GR-driven transcription. In addition, hnRNP U repression
      of glucocorticoid induced transcription was found to be dependent on the amount
      of cotransfected GR, where a high amount of GR leads to ligand-inducible
      repression of GR-dependent reporter gene activity by hnRNP U, whereas low amounts
      of GR showed nearly no effect. The relative concentrations of GR, hnRNP U and DNA
      binding sites for GR are important for the effect of hnRNP U on transcription,
      suggesting a model where hnRNP-U acts as a storage site for intranuclear GR.

PMID- 11530287
TI  - Steroidogenesis in the human skin: 21-hydroxylation in cultured keratinocytes.
AB  - We have evaluated the metabolism of radiolabeled progesterone (P) by the
      microsomal fraction isolated from HaCaT keratinocytes. P was widely metabolized
      to different compounds that included DOC (5-7% conversion) thus demonstrated 21
      hydroxylase (21-OHase) activity, a key step in adrenal synthesis of gluco- and
      mineralocorticoids. However, RT-PCR amplification for the CYPc21 transcript of
      the corresponding gene showed no evidence for gene expression in HaCaT cells
      suggesting that the 21-OHase enzyme present in keratinocytes is different from
      that described in adrenal gland. Further characterization showed that whereas
      estradiol stimulated markedly P metabolism by HaCaT microsomes, with generation
      of new unidentified compounds, Lineweaver-Burk analysis of keratinocyte 21-OHase
      activity showed that the K(m) and V(max) were unaffected by estrogen. The
      apparent K(m) was 0.6 microM without estradiol and 0.7 microM with estradiol,
      while the respective V(max) values were 60 and 76 nmol/l/min. To conclude, we
      found extensive metabolism of P in human keratinocytes, we also provide the first
      demonstration of 21-OHase activity in this cell system and further showed that it
      is coded by a gene different from the adrenal CYPc21.

PMID- 11530286
TI  - Estrogenic activity of two standardized red clover extracts (Menoflavon) intended
      for large scale use in hormone replacement therapy.
AB  - Isoflavones are the most potent estrogenic compounds in red clover extracts.
      Standardized extracts have been discussed as an alternative for hormone
      replacement therapy. Variation due to extraction procedure and natural seasonal
      variation and variations originating from agricultural conditions have prevented
      the large scale use of such phytochemicals. An improved extraction procedure and
      careful analysis of the raw material yielded in a highly standardized preparation
      (Menoflavon) with an average isoflavone content of approximately 9% (dry weight)
      determined by HPLC. The estrogenic activity has been further evaluated by a yeast
      two plasmid system using estrogen receptor alpha (ER alpha) and estrogen receptor
      beta (ER beta). An estrogenic activity corresponding to a transactivational
      capacity of ca. 18 microg 17 beta-estradiol per g red clover extract for ER alpha
      and ca. 78 microg 17 beta-estradiol per g red clover for ER beta was obtained.
      The difference is explained by the higher affinity of ER beta to isoflavones than
      that observed for ER alpha. Calculation of potency from isoflavone content
      measured by HPLC yielded a comparable potency to that experimentally determined
      by the bioassay. The high content of isoflavones as well as the higher
      transactivational potency for ER beta than ER alpha make these extracts
      interesting candidates for HRT.

PMID- 11530288
TI  - Estrogenic influence on the regulation of hepatic estrogen receptor-alpha and
      serum level of angiotensinogen in female rats.
AB  - The majority of data regarding biological effects of estrogens is based on
      studies in male rats or ovariectomized (Ovx) female rats. Therefore, in this
      study, the effects of estradiol treatment on the regulation of the hepatic
      estrogen receptor and the level of circulating angiotensinogen were examined in
      the intact female rat. The data were compared with that of the hypophysectomized
      (Hx) rat. Animals were treated with either low (physiological) or high
      (pharmacological) doses of estrogen. In intact rats, the hepatic estrogen
      receptor (ER) level increased with increasing doses of estrogen. This was in
      contrast to the Hx rats where growth hormone (GH) and dexametasone (Dex) in
      combination were the sole modulators of the estrogen receptor. The
      angiotensinogen level increased in normal rats after estrogen administration in a
      dose dependent manner, regardless of the mode of administration. The pure
      antiestrogen ICI 182 780 efficiently blocked the increase in circulating
      angiotensinogen. The conclusion is that in the normal female, estrogens are
      important modulators of the serum angiotensinogen level.

PMID- 11530289
TI  - Ontogeny of steroid metabolizing enzymes in rat oligodendrocytes.
AB  - Rat oligodendroglial cells were isolated from newborn and developing brains and
      used immediately after, for quantification of steroid metabolizing activities.
      Oligodendrocytes (Ol) and their progenitor cells were incubated with [(14)C]
      testosterone, [(14)C] progesterone, [(14)C] pregnenolone or [(14)C]
      dehydroepiandrosterone (DHEA). Oligodendrocytes and their progenitor cells
      expressed different steroid metabolizing enzymes. The main activities were 5
      alpha reduction of testosterone and progesterone and 3 beta hydroxy steroid
      dehydrogenase-isomerase which transformed pregnenolone into progesterone and DHEA
      into Delta 4 androstenedione. 5 alpha reductase activity increased in male and
      female rats in parallel with testosterone or progesterone. Contrary to this, 3
      beta hydroxysteroid dehydrogenase-isomerase activity was found to be high in the
      young rat and to decrease when testosterone and progesterone plasma concentration
      increased.

PMID- 11530290
TI  - Comparison of progesterone concentration determination by 12 non-isotopic
      immunoassays and gas chromatography/mass spectrometry in 99 human serum samples.
AB  - A single serum progesterone determination may be highly predictive for early
      pregnancy and in vitro fertilisation and embryo-transfer outcomes. We therefore
      compared 12 direct non-isotopic progesterone immunoassays with gas
      chromatography/mass spectrometry (GC/MS). For each assay, data from the analysis
      of 99 individual sera were compared with data obtained by GC/MS, using regression
      and bias plot analyses and the ratio method. We observed a larger difference in
      concentration between high and low values and a broader distribution of results
      for immunoassays than for GC/MS. All immunoassays displayed bias in the
      calibration process and a lack of specificity and/or sensitivity, to various
      degrees. We tried to identify the parameters of the assay procedure that might
      contribute to these discrepancies. None of the criteria investigated (antibodies,
      control and preparation of calibrators, blocking agents and choice of tracer) had
      a significant effect when studied alone.

PMID- 11530292
TI  - Methods to profile gene expression.
AB  - Molecular biology has been influenced tremendously by recent technological
      advancements in miniaturization and automation. One consequence has been the
      development of robust and sensitive methods to analyze gene expression. The
      ability to evaluate systematically the expression of every mammalian gene is now
      technically feasible. The methods available for gene expression profiling, and
      their application in cardiovascular research, are the topics of this review.

PMID- 11530293
TI  - High-throughput screening strategies for cardiac ion channels.
AB  - In this article we discuss new technologies for high-throughput screening (HTS)
      of cardiac ion channels. We review the current state of cell based HTS and
      discuss new technologies and approaches using voltage-sensing Fluorescence
      Resonance Energy Transfer (FRET) dyes and "native" cell lines. The advantages and
      disadvantages of a gene-centric approach in which a target protein is
      overexpressed in a non-native cell line are addressed and the role of such
      primary screens in the drug discovery process outlined. Primary and secondary
      screens using "native" type cell lines either endogenously expressing the ion
      channel of interest or overexpressing it are discussed with respect to HTS
      capacity and sensitivity for FRET voltage sensing dyes and other technologies.
      Finally the advantages and approaches of screening against multiple targets in an
      endogenous cardiac cell line are discussed.

PMID- 11530294
TI  - The heart SNPs a beat: polymorphisms in candidate genes for cardiovascular
      disease.
AB  - Several environmental risk factors of cardiovascular disease are well
      established, but genetic risk alleles contributing to the disease in the general
      population are hotly debated. New strategies focusing on polymorphism discovery
      in candidate disease genes followed by tests of association to genes across the
      genome offer a pioneering approach to identifying risk alleles. Several hundred
      candidate genes for cardiovascular disease have been screened for common
      polymorphisms and these variants may provide susceptibility alleles which largely
      contribute to risk of cardiovascular disease in the general population. However,
      the impact of common susceptibility alleles for disease management will depend on
      many years of future investigation.

PMID- 11530295
TI  - Application of proteomics to the study of cardiovascular biology.
AB  - Proteomics involves the integration of a number of technologies with the aim of
      analyzing the complete complement of proteins expressed by a biological system in
      response to various stimuli and/or under different physiological or
      pathophysiological conditions. Recent technical improvements to the methods
      employed for protein separation and protein identification have resulted in a
      dramatic increase in the number of proteomics-based research projects. More
      importantly, it has become readily apparent that examining changes in the
      proteome offers insight into understanding cellular and molecular mechanisms that
      cannot be obtained through genomic analysis. There are numerous examples of
      cardiovascular functions whose molecular pathways are mediated through post
      translational processes such as phosphorylation. The use of proteomics offers the
      ability to simultaneously monitor the changes in protein expression and/or cell
      signaling pathways in response to such conditions as cardiac hypertrophy and
      heart failure. Together with complementary genomic data, proteomics-based
      research can greatly increase our understanding of cardiovascular biology.

PMID- 11530296
TI  - Genomic and proteomic databases: large-scale analysis and integration of data.
AB  - With the completion of the human genome draft sequencing and assembly, an
      upcoming targeted goal will be identifying the proteins and changes in protein
      expression, which are derived from the genome template. There is important
      information already available on many proteins that can be a valuable resource to
      scientists in cardiovascular medicine as well as other fields. This article will
      summarize many of the different databases, their content and growth, and the
      differences between growth of nucleic acid and protein databases. Linkage between
      and integration of different protein and nuclei acid databases, along with
      related annotation, will greatly improve the information content and knowledge
      base with regards to protein data.

PMID- 11530297
TI  - Phenotype-driven genetic approaches in mice: high-throughput phenotyping for
      discovering new models of cardiovascular disease.
AB  - Cardiovascular diseases such as hypertension, atherosclerosis, cardiac
      hypertrophy homocysteinemia and arrhythmias impose great health, social and
      financial costs. Some of these diseases are single gene traits that segregate in
      a simple Mendelian manner. Most are genetically complex, however, and result from
      combinations of large numbers of genes (polygenic and epistatic traits) or from
      interactions between genetic and environmental factors (multifactorial traits).
      Insights into the genetic control of these diseases could lead to improved
      diagnosis and treatment as well as a deeper understanding of basic physiological
      processes.

PMID- 11530298
TI  - HIV research in American youth.

PMID- 11530299
TI  - The REACH (Reaching for Excellence in Adolescent Care and Health) project: study
      design, methods, and population profile.

PMID- 11530300
TI  - The ACCESS (Adolescents Connected to Care, Evaluation, and Special Services)
      project: social marketing to promote HIV testing to adolescents, methods and
      first year results from a six city campaign.

PMID- 11530301
TI  - The TREAT (Therapeutic Regimens Enhancing Adherence in Teens) program: theory and
      preliminary results.

PMID- 11530302
TI  - Immunology and the REACH study: HIV immunology and preliminary findings. Reaching
      for Excellence in Adolescent Care and Health.
AB  - This review paper presents the immunology findings in human immunodeficiency
      virus (HIV) infected and uninfected youth in the Reaching for Excellence in
      Adolescent Care and Health (REACH) Project within the context of basic and HIV
      immunology concepts. Methods employed in the study for specimen collection,
      management, and laboratory analysis are presented. This paper reviews published
      analyses of cross-sectional data; longitudinal analyses are underway. These
      preliminary data extend the work of others in demonstrating the potential for
      substantial thymic reserve in youth. This finding in HIV infected adolescents has
      implications for a fuller response to antiretroviral or immune-based therapies
      compared to that seen in adults. Dysregulation in mucosal immunity may appear
      before systemic HIV effects are seen and requires attention particularly to
      screening and treatment of genital co-infections. REACH has demonstrated gender
      differences in immunologic measures irrespective of HIV infection status.

PMID- 11530303
TI  - Sexually transmitted infections among HIV infected and HIV uninfected high-risk
      youth in the REACH study. Reaching for Excellence in Adolescent Care and Health.
AB  - OVERVIEW: This review presents the findings of published research in the Reaching
      for Excellence in Adolescent Care and Health (REACH) Project on sexually
      transmitted infections (STIs) within the context of the project's scientific
      agenda. Methods employed in the study for specimen collection, management, and
      laboratory analysis are presented. This review presents published analyses of
      cross-sectional data; longitudinal analyses are underway. In addition, baseline
      prevalence data on selected STIs and sexual risk profiles of the subjects in
      REACH are presented. High STI rates were evident in both human immunodeficiency
      virus (HIV) infected and uninfected youth of both genders regardless of sexual
      orientation. High infection rates at baseline suggest that prevention-oriented
      programs for risk reduction among adolescents should focus on both HIV infected
      and at-risk, uninfected youth.

PMID- 11530304
TI  - No change in health risk behaviors over time among HIV infected adolescents in
      care: role of psychological distress.
AB  - PURPOSE: To investigate the association of psychological distress and health risk
      behaviors among HIV infected adolescents. It was hypothesized that higher levels
      of distress would be associated with increased sexual risk behaviors, and
      increased use of alcohol and drugs. METHODS: HIV infected adolescents (N = 323)
      were recruited into an observational study in 15 clinical sites; for the 323
      subjects, a total of 1212 visits were used in a repeated measures analysis. Data
      on depression (using the CES-D), anxiety (manifest anxiety scale), sexual
      behaviors and alcohol and marijuana use were obtained through computer-assisted
      self-administered interview. RESULTS: Approximately 65% of the sample was
      sexually active across all six study visits, with approximately 43% consistently
      reporting having unprotected sex at last intercourse. Higher levels of depression
      were associated with frequent alcohol use and with unprotected sex at last
      intercourse, with depressed adolescents significantly more likely to have had
      unprotected sex than those who were not depressed. Health anxiety was associated
      with frequent marijuana use and with recent sexual activity, and physiological
      anxiety was also associated with recent sexual activity. CONCLUSIONS: Despite the
      fact that these HIV infected adolescents are all engaged in primary care, overall
      the sample is maintaining its high-risk sexual behavior. In addition, these
      adolescents may be self-medicating to deal with health-related anxiety. Health
      interventions for HIV infected adolescents should examine whether psychological
      distress is contributing to maintenance health risk behaviors.

PMID- 11530305
TI  - The relationship of unsafe sexual behavior and the characteristics of sexual
      partners of HIV infected and HIV uninfected adolescent females.
AB  - PURPOSE: To compare characteristics of sexual relationships in HIV infected and
      HIV uninfected female adolescents and their association with condom use. METHODS:
      HIV infected and uninfected subjects, aged 13-19 years, were enrolled in a
      prospective HIV study from 15 sites in 13 U.S. cities. Baseline data on
      demographic information, substance use, sexual behavior, partner information, and
      condom use were collected through direct and computer-assisted interviews from
      currently sexually active females. Univariate, multiple logistic regression, and
      repeated measures analyses were employed. RESULTS: Data from 153 HIV infected and
      90 HIV uninfected female subjects showed, on average, that current partners were
      4-6 years older. In multivariate analysis, HIV infected subjects were older (OR =
      1.37; 95% CI: 1.04-1.81), had more lifetime partners (OR = 2.23; 95% CI: 1.03
      4.82), initiated consensual vaginal sex earlier (OR = .74; 95% CI:.58-.95),
      perceived partner to also be HIV infected (OR = 7.46; 95% CI: 3.2-17.4), and had
      less unprotected sex (OR = .27; 95% CI:.16-.45). Length of relationship was
      associated with more unprotected sex for both HIV infected and uninfected
      subjects (OR = 2.59, 95% CI: 1.27-5.27, OR = 4.13; 95% CI: 1.31-13.05,
      respectively). Mean partner age difference was greater among HIV infected than
      for HIV uninfected (OR = 1.06; 95%CI: 1.01-1.12); this greater age difference for
      HIV infected females was associated with less protection (OR = 1.09; 95% CI: 1.03
      1.15). HIV disclosure influenced condom use: without disclosure, less condom use
      was reported (OR = 6.8; 95% CI: 2.29-20.24) controlling for perception that
      partner was also HIV infected (OR = 1.1; 95% CI: 1.02-1.21). CONCLUSIONS: Because
      age differential influenced reported condom use, more research, particularly
      qualitative, is needed into the dynamics of these relationships. Prevention
      efforts must address partners, particularly older ones.

PMID- 11530306
TI  - Disclosure of serostatus by HIV infected youth: the experience of the REACH
      study. Reaching for Excellence in Adolescent Care and Health.
AB  - PURPOSE: To describe disclosure of HIV serostatus by infected youth to parents
      and sexual partners and to examine the association of disclosure with subject
      characteristics. METHODS: Baseline data on 317 HIV infected adolescents in
      national 15 site study were examined. Data sources included direct and computer
      assisted interview, laboratory studies, and chart reviews. Examination of
      parental disclosure was restricted to subjects without parental permission
      requirements. Concordance in parental disclosure/support used McNemar's test.
      Associations between disclosure to parent(s) and subject characteristics were
      examined using logistic regression analysis. Repeated measure analysis was used
      for sexual partner disclosure. RESULTS: Subjects of both genders more often
      disclosed their HIV infection status to mothers than to their fathers (77% vs.
      47%, p < .001). With disclosure, perceived support from either parent was high.
      In multivariate analyses, factors associated with maternal disclosure were length
      of time since diagnosis (OR = 1.43; 95% CI: 1.06-1.92), and Hispanic ethnicity
      (OR = .37; 95% CI: .15-.95). No factors were significantly associated with
      paternal disclosure in multivariate analysis, although length of time since
      diagnosis showed a trend (OR = 1.31; 95% CI: 1.00-1.74). Factors associated with
      disclosure to sexual partners were partner's HIV+ status (OR = 2.09; 95% CI: 1.11
      3.93) and "main partner" status (OR = 3.17; 95% CI: 1.84-5.46). CONCLUSIONS:
      Although subjects were more likely to reveal their status to their mothers,
      parental support was perceived as high after disclosure to either parent. Since
      "time since diagnosis" was associated with parental disclosure, support systems
      are necessary for youth until such a disclosure can occur.

PMID- 11530307
TI  - Douching practices among HIV infected and uninfected adolescents in the United
      States.
AB  - PURPOSE: To characterize sexual behaviors and sociodemographic factors that are
      associated with douching among geographically diverse adolescent women with and
      without HIV infection. METHODS: HIV infected subjects recruited preferentially
      and behaviorally comparable high-risk HIV uninfected subjects were enrolled in a
      prospective HIV study from 15 sites in 13 U.S. cities. Baseline interview data
      from 1996 to 1999 for females aged 12 to 19 years were analyzed using one-way
      analysis of variance and multiple logistic regression. RESULTS: Among the 342
      females/young women, 74.9% were black (non-Hispanic), 11.1% Hispanic/Latina, and
      14.0% white or other race/ethnicity; 63.5% were HIV infected. Young women who had
      dropped out of high school comprised 23.4% of subjects. In the 3 months before
      the interview, 179 (52.3%) adolescents had douched at least once. In a
      multivariable logistic regression model, recent douching was more common among
      sexually active females (OR = 2.2; 95% CI: 1.2-4.2), Blacks (OR = 2.2; 95% CI:
      1.2-4.1 vs. Hispanics/Whites/others), females who dropped out of high school (OR
      = 2.1; 95% CI: 1.2-3.7), and HIV infected females (OR = 1.7; 95% CI: 1.04-2.7).
      CONCLUSIONS: In this nationwide study, adolescents who are sexually active,
      African-American, dropped out of high school, and HIV infected were most likely
      to douche. Interventions to discourage douching should pay special attention to
      these populations.

PMID- 11530308
TI  - Correlation between urine and cervical specimens for the detection of cervical
      Chlamydia trachomatis and Neisseria gonorrhoeae using ligase chain reaction in a
      cohort of HIV infected and uninfected adolescents.
AB  - PURPOSE: (a) To examine the concordance between ligase chain reaction (LCR)
      results from urine and cervical samples for Chlamydia trachomatis and Neisseria
      gonorrhoeae in HIV infected and uninfected adolescent women, and (b) to examine
      factors that may influence the concordance of LCR results in this population.
      METHODS: Baseline specimens from 269 of 334 female subjects enrolled in a
      longitudinal study of HIV infection in adolescents were analyzed for C.
      trachomatis and N. gonorrhoeae using ligase chain reaction (LCR) assays in a
      central laboratory. Concordance was measured using kappa coefficient with
      permutation analyses to calculate the difference between HIV status groups.
      Discordant LCR results were examined for the co-infection with the other
      microorganism, bacterial vaginosis, or Trichomonas vaginalis. RESULTS: The
      prevalence of C. trachomatis detected by LCR in the HIV infected and uninfected
      groups was 19.3% and 12.2%, respectively (p = .16); the prevalence of N.
      gonorrhoeae was 7.0% and 2.4%, respectively (p = .16). Urine LCR assay
      sensitivity to detect cervical C. trachomatis infection was 86% (95% CI: 68%-96%)
      in the HIV infected group and 100% (95% CI: 69%-100%) in the HIV uninfected
      group. Urine LCR assay sensitivity to detect cervical N. gonorrhoeae infection
      was 92% (95% CI: 62%-100%) in the HIV infected group. There were only 2 N.
      gonorrhoeae infections in the HIV uninfected group, and both were urine LCR
      positive. Differences in sensitivity between HIV infected and HIV uninfected
      subjects were not statistically significant. Coinfection with N. gonorrhoeae,
      bacterial vaginosis or Trichomonas vaginalis was not associated with the
      concordance of urine and cervical LCR results. CONCLUSION: The relatively high
      sensitivity of urine LCR testing overall suggests that urine screening may be
      reasonable for sexually active adolescent females with or without HIV infection
      in situations in which urine screening may be more acceptable than pelvic
      examinations.

PMID- 11530309
TI  - Contraceptive choices in HIV infected and HIV at-risk adolescent females.
AB  - PURPOSE: To describe reported contraception use in HIV infected and HIV
      uninfected but at-risk female adolescents, and determine associations with the
      reported consistent use of effective contraception methods, including its
      association with pregnancy. METHODS: HIV infected and at-risk female youth, aged
      13-18 years, who were sexually active and reporting no intention to become
      pregnant, were included. Contraception use data from three consecutive visits
      (approximately 6 months apart) were used. RESULTS: Ninety-four percent of HIV
      infected and 89% of at-risk subjects reported choosing a main contraception
      method with demonstrated efficacy when used consistently. Approximately 50% chose
      partner condoms. HIV infected youth were more likely to report 100% partner
      condom use in the past 3 months (73% vs. 46%; OR 3.3; 95% CI: 1.7-5.6). At-risk
      youth were 2.5 times more likely than HIV infected subjects to report using
      nothing (95% CI: 1.1-5.8). Slightly more than half (56%) demonstrated the
      consistent reporting of effective methods (CREM) of contraception. In
      multivariate analysis, HIV infection (OR 4.0; 95% CI: 2.2-8.2) and African
      American race (OR 2.7; 95% CI: 1.1-6.6) were significantly associated with CREM.
      Subjects reporting inconsistent or unreliable contraception use had higher 1-year
      pregnancy rates than CREM subjects (32% vs. 14%; p = .002). CONCLUSIONS: Only
      half of HIV infected and at-risk youth reported using effective contraception
      consistently, despite its availability. Additionally, regardless of reported
      contraceptive use, the rates of unplanned pregnancy were unacceptably high.

PMID- 11530310
TI  - Incident pregnancy rates in HIV infected and HIV uninfected at-risk adolescents.
AB  - PURPOSE: To compare pregnancy incidence between HIV infected and HIV uninfected
      adolescents over a 3-year period and to characterize factors that differentiate
      pregnant from nonpregnant HIV infected females. METHODS: Female adolescents
      enrolled in Reaching for Excellence in Adolescent Care and Health (REACH), a
      national cohort study, and nonpregnant at baseline comprised the sample (n =
      345). Subject information on pregnancy, risk behavior, and psychosocial
      characteristics was obtained through interview, chart review, physical
      examination and laboratory data collected every 3 months. Incident pregnancy rate
      was analyzed using Cox proportional hazards modeling; the predictors of incident
      pregnancy were evaluated using repeated measures analysis. RESULTS: Ninety-four
      pregnancies were identified over 3 years. No significant difference in pregnancy
      incidence was detected between HIV infected and uninfected females (20.6 and 28.4
      per 100 person-years, respectively, p = .16). However, for adolescents with
      living children at entry, HIV infected females were significantly less likely to
      become pregnant than HIV uninfected (HR = .45; p = .03). Among HIV infected
      adolescents, significant predictors of incident pregnancy were older age (p =
      .01) and not using hormonal contraception (p = .00), whereas increased spiritual
      hope and passive problem-solving capacity were protective against pregnancy (p =
      .02, and.05, respectively). Multivariate analysis revealed pregnancy prior to
      study entry to be predictive for (OR = 3.0; 95% CI: 1.2-7.7), and increased
      spiritual hope to be protective (OR = .4; 95% CI: .2-.9) against incident
      pregnancy in HIV infected females without the hormonal contraceptive variable in
      the model. CONCLUSIONS: The pregnancy rate is high in this study population.
      Further research is needed into its determinants and attenuating factors,
      particularly the role of spiritual elements, to design better contraceptive
      services and reproduction-related education targeting high-risk youth.

PMID- 11530311
TI  - HIV-related oral manifestations among adolescents in a multicenter cohort study.
AB  - PURPOSE: To describe baseline prevalence of oral mucosal diseases among HIV
      infected adolescents in relationship to biological and behavioral risk factors.
      METHODS: Participants in Reaching for Excellence in Adolescent Care and Health
      (REACH), a multicenter longitudinal observational study of HIV/AIDS in
      adolescents, received physical examinations, blood tests, and oral examinations
      at 3-month intervals. We evaluated participants for oral conditions commonly seen
      in relationship to HIV, and explored the association of the most common lesion
      with selected biological and behavioral variables at baseline using contingency
      tables and Fisher's Exact test. RESULTS: Among 294 HIV infected adolescents
      recruited between March 1996 and March 1999, the majority were female (75%), aged
      17 to 18 years (69%), and African-American (73%). More than 90% had a CD4(+) T
      lymphocyte count > 200 cells/mm(3) at baseline and 57% had a plasma HIV-1 RNA
      concentration <or=5000 copies/mL. The most common condition was oral candidiasis
      (6%), predominantly the pseudomembranous type. The only variable found to be
      associated with oral candidiasis was elevated plasma HIV-1 RNA concentration (p =
      .03). Aside from 2 cases of hairy leukoplakia and aphthous ulcers, no other oral
      mucosal lesions were identified in this subject population with apparently early
      HIV disease. CONCLUSION: Similar types of oral lesions were observed in HIV
      infected adolescents as have been seen in adults, although the prevalence of
      these lesions was low. Elevated plasma HIV-1 RNA concentration was found to be
      associated with the baseline prevalence of oral candidiasis, and appeared to be a
      better predictor of HIV-related oral disease than CD4(+) T cell count in this
      cohort at early stage of HIV disease.

PMID- 11530312
TI  - The association of perceived health, clinical status, and initiation of HAART
      (highly active antiretroviral therapy) in adolescents.
AB  - PURPOSE: To examine factors associated with the initiation of highly active
      antiretroviral therapy (HAART) in adolescents to understand better how current
      National Institutes of Health (NIH) Guidelines are being used in practice.
      METHODS: HIV infected and HAART-naive adolescents seen at 15 REACH clinical sites
      were selected. Repeated measures methodology using generalized estimating
      equations was applied to identify associations between subject demographic
      characteristics, risk behaviors, perceived health, and clinical status with the
      outcome measure of HAART initiation during the first 24 study months. RESULTS: A
      total of 219 subjects were eligible for analysis; HAART was prescribed in 115
      (53%). Significant univariate associations with HAART prescription included lower
      CD4(+) T cell counts (OR = 1.7, 95% CI: 1.1-2.6), higher viral loads (OR = 2.7,
      95% CI: 1.5-5.0), and calendar year of HAART prescription (OR as high as 2.4, 95%
      CI: 1.1-5.2). Multivariate results showed that after controlling for CD4(+) T
      cell counts below 500 cells/mm(3), higher plasma HIV-1 RNA (<or=10,000 copies per
      ml), and temporal factors, having a high school diploma/GED but no further
      education (OR = 2.7, 95% CI: 1.3-5.5) and subject's perception of poor health
      status (OR = .987; 95% CI: .975- .999) were independently associated with
      prescription of HAART. HAART was most likely to be prescribed during the first
      half of 1998 in this cohort (OR = 10.8; 95% CI: 4.0-29.0). CONCLUSIONS: In this
      first ever study of HAART prescription in adolescents infected with HIV,
      perception of poor health status and having a high school diploma/GED were
      independently associated with prescription of HAART suggesting that the personal
      decision to accept therapy is related to the belief that one's health is
      deteriorating and that the decision to prescribe therapy may be linked in some
      fashion to the prescriber's assessment of the patient's ability to master the
      regimen as well as clinical status.

PMID- 11530313
TI  - Serologic response to hepatitis B vaccine in HIV infected and high-risk HIV
      uninfected adolescents in the REACH cohort. Reaching for Excellence in Adolescent
      Care and Health.
AB  - PURPOSE: To evaluate hepatitis B (HBV) vaccine response rates in HIV infected and
      high-risk HIV uninfected youth and examine associations with responsiveness in
      the HIV infected group. METHODS: Cohorts within the Reaching for Excellence in
      Adolescent Care and Health (REACH) study population were defined based on receipt
      of HBV vaccine both retrospectively and prospectively. Sero-responsiveness was
      determined by HBsAb measurements. Testing was done for HBsAg, HBsAb, and HBcAb.
      For HBsAb, a value of > 10 International Units per liter was considered a
      positive response, and the data were collected as either positive or negative
      from each of the reporting laboratories. Covariates of responsiveness were
      explored in univariate and multivariate models for each cohort. RESULTS: Sixty
      one subjects had received a three-dose vaccination course at the time of entry
      into REACH. HIV uninfected subjects had significantly higher rates of response by
      serology compared with HIV infected subjects (70% vs. 41.1%; chi(2) = .05; RR =
      .586, 95% CI: .36-.96). By the time of an annual visit 43 subjects had received
      three vaccinations with at least one occurring in the study period. The rates of
      response were similar for the HIV infected and uninfected groups (37.1% vs.
      37.5%) in this cohort. Univariate and multivariate analysis in the prospective
      HIV infected group (N = 35) found an association between elevated
      CD8(+)/CD38(+)/HLA-DR(+) T cells and lack of HBV vaccine responsiveness (6.7% vs.
      60%; chi(2) = .03; RR = .12, 95% CI: .02- .55). CONCLUSIONS: The poor HBV vaccine
      response rate in the HIV uninfected high-risk adolescents was unexpected and
      suggests that HBV vaccination doses have not been optimized for older
      adolescents. This is the first report of decreased responsiveness in HIV infected
      subjects being associated with elevated CD8(+)/CD38(+)/HLA(-)DR(+) T cells and
      suggests that ongoing viral replication and concomitant immune system activation
      decreases the ability of the immune system in HIV infected subjects to respond to
      vaccination.

PMID- 11530314
TI  - A doctor's journey: tribute to a precious one. A patient who volunteered for the
      REACH study.

PMID- 11530315
TI  - HLA and AIDS: a cautionary tale.
AB  - The human major histocompatibility complex HLA has been implicated repeatedly as
      a regulator of the outcome of HIV exposure and infection. A new study of long
      term survivors who naturally depress HIV-1 replication and avoid the signs of
      AIDS for years after infection suggests that homozygosity for a group of HLA-B
      locus alleles termed Bw4 confers resistance, ostensibly by regulating natural
      killer cell-ligand interactions. However, close inspection of the accumulated
      evidence raises some questions and urges validation of the potential Bw4 effects
      in additional studies.

PMID- 11530316
TI  - Genes, proteins and brain disease.

PMID- 11530317
TI  - Acetylation can regulate cell-cycle progression.

PMID- 11530318
TI  - Do telomeres help define the genes expressed during ageing?

PMID- 11530319
TI  - Immunization for Alzheimer's disease: yet closer to clinical trials.

PMID- 11530320
TI  - Hereditary haemochromatosis: more causative genes.

PMID- 11530333
TI  - Processing and presentation of antigens by dendritic cells: implications for
      vaccines.
AB  - Dendritic cells (DCs) are potent antigen-presenting cells that are specialized in
      initiation of T-cell immunity. DCs induce promising anti-tumor T-cell and
      clinical responses, apparently without significant toxicity. Under certain
      conditions, DCs even silence T-cell immune responses in vivo. This dual capacity
      to modulate the immune system uniquely positions DCs for the treatment of
      autoimmunity, cancer and chronic viral infections.

PMID- 11530334
TI  - Prospects for prevention and treatment of cancer with selective PPARgamma
      modulators (SPARMs).
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma), a nuclear receptor
      and transcription factor that regulates the expression of many genes relevant to
      carcinogenesis, is now an important target for development of new drugs for the
      prevention and treatment of cancer. Deficient expression of PPARgamma can be a
      significant risk factor for carcinogenesis, although in some cases overexpression
      enhances carcinogenesis. Ligands for PPARgamma suppress breast carcinogenesis in
      experimental models and induce differentiation of human liposarcoma cells. By
      analogy to the selective estrogen receptor modulator (SERM) concept, it is
      suggested that selective PPARgamma modulators (SPARMs), designed to have desired
      effects on specific genes and target tissues without undesirable effects on
      others, will be clinically important in the future for chemoprevention and
      chemotherapy of cancer.

PMID- 11530335
TI  - Thrombospondins and tumor angiogenesis.
AB  - The thrombospondins (TSPs) are a family of five secreted proteins that are widely
      distributed in the extracellular matrix of numerous tissues. TSPs are
      multimodular and each domain specifies a distinct biological function through
      interaction with a specific receptor. TSP1 and TSP2 have anti-angiogenic
      activity, which, at least for TSP1, involves interaction with the microvascular
      endothelial cell receptor CD36. Expression of TSP1 and TSP2 is modulated by
      hypoxia and by oncogenes. In several tumors (thyroid, colon, bladder carcinomas),
      TSP1 expression is inversely correlated with tumor grade and survival rate,
      whereas in others (e.g. breast carcinomas), it is correlated with the stromal
      response and is of little prognostic value. Recent studies suggest that TSPs or
      TSP-derived peptides retaining biological activity could be developed into
      promising new therapeutic strategies for the anti-angiogenic treatment of solid
      tumors.

PMID- 11530336
TI  - Alcoholic liver disease: new insights into mechanisms and preventative
      strategies.
AB  - Alcoholic liver disease has a known aetiology but a complex pathogenesis. It is
      an extremely common disease with a high mortality, but the reason why only a
      relatively small proportion of heavy drinkers progress to advanced disease
      remains elusive. Accumulating evidence points towards an elaborate interplay
      between metabolism, inflammation and immunity in the development of steatosis,
      hepatitis and fibrosis. These complex pathways leading to liver injury offer many
      potential susceptibility loci, as well as sites for potential therapeutic
      intervention.

PMID- 11530337
TI  - Unfolding retinal dystrophies: a role for molecular chaperones?
AB  - Inherited retinal dystrophy is a major cause of blindness worldwide. Recent
      molecular studies have suggested that protein folding and molecular chaperones
      might play a major role in the pathogenesis of these degenerations. Incorrect
      protein folding could be a common consequence of causative mutations in retinal
      degeneration disease genes, particularly mutations in the visual pigment
      rhodopsin. Furthermore, several retinal degeneration disease genes have recently
      been identified as putative facilitators of correct protein folding, molecular
      chaperones, on the basis of sequence homology. We also consider whether
      manipulation of chaperone levels or chaperone function might offer potential
      novel therapies for retinal degeneration.

PMID- 11530338
TI  - Disease model: heritable skin blistering.
AB  - Hereditary skin blistering disorders comprise a group of genodermatoses whose
      common primary feature is the formation of blisters following minor trauma.
      Examples of such conditions include epidermolysis bullosa and several bullous
      forms of ichthyosis. Distinct mutations in various genes encoding intra- and
      extra-cellular structural components of the skin reflect the clinical
      heterogeneity of these disorders. Several animal models are currently used to
      study the role of these molecules in the disease process. Some of these models
      will find their place in evaluating new therapeutic strategies for this
      devastating group of diseases.

PMID- 11530339
TI  - Packaged merozoite release without immediate host cell lysis.
AB  - In spite of the extraordinary progress in unravelling the genome of the
      Plasmodium falciparum parasite, many crucial aspects of its biology remain poorly
      understood. One largely neglected area is the mechanism of merozoite release from
      host red blood cells.

PMID- 11530340
TI  - Trapping parasite secretory proteins in baker's yeast.
AB  - Because the function of signal sequences has been conserved during evolution it
      has been possible to develop both bioinformatics resources to identify them and
      techniques to clone genes that encode secretory proteins. The latter entail
      insertion of heterologous signals upstream of signal peptide deleted reporter
      genes. We discuss the advantages of using Saccharomyces cerevisiae for signal
      sequence trap technology. The yeast protein-translocation system appears to be
      less discriminating than that of higher eukaryotes - for example, a Theileria
      parva cysteine protease gene containing a recessed, nonclassical signal allows
      access to the secretory pathway--and yeast technology could have general
      application in studying elements of parasite protein trafficking.

PMID- 11530342
TI  - Population genetics and drug resistance in nematode.

PMID- 11530352
TI  - Are trials in New World monkeys on the critical path for blood-stage malaria
      vaccine development?
AB  - The development of malaria blood-stage vaccines is gathering momentum: there are
      several new funding initiatives, one multiantigen formulation is currently being
      tested and at least one other blood-stage vaccine is expected to begin trials in
      2001. However, there is no consensus over the best way to select which form of an
      antigen to take into clinical testing. There is thus a danger that less-effective
      vaccines might be tested in the field in the order of their availability, rather
      than merit. Here, we argue that first proving efficacy in the New World monkey
      challenge model would accelerate development.

PMID- 11530353
TI  - New World monkey efficacy trials for malaria vaccine development: critical path
      or detour?
AB  - Neither GMP malaria antigens nor GMP vaccines have been compared for efficacy in
      monkeys and humans. It is too risky to base categorical (go/no go) development
      decisions on results obtained using partially characterized (non-GMP) antigens,
      adjuvants that are too toxic for human use or unvalidated primate models. Such
      practices will lead to serious errors (e.g. failure to identify and stop flawed
      efforts, rejection of effective vaccine strategies) and unjustifiable delays.
      Successful malaria vaccine development will emphasize definitive field trials in
      populations at risk of malaria to define and improve vaccine efficacy.

PMID- 11530354
TI  - Telomere biology of trypanosomatids: more questions than answers.
AB  - Trypanosomatids are severe pathogens in developing countries, where they affect
      both humans and domestic animals. Factors intrinsic to the host, the toxicity or
      subcurative effects of the available antiparasite medication and the low
      perspective of potential vaccines favor research on novel candidates for drug
      target. Telomeres are essential for the survival of most eukaryotes. In
      trypanosomatids, events such as antigenic variation and/or gene conversion and
      duplication occur at telomeric positions, possibly facilitating genome
      rearrangement. Understanding the role that telomere maintenance might play in the
      cell life span of trypanosomatids has important implications for therapeutics of
      parasitic diseases.

PMID- 11530355
TI  - Models for the population biology and control of human onchocerciasis.
AB  - The absence of animal models in which to reproduce successfully the complete life
      cycle of Onchocerca volvulus has hindered progress towards unravelling the
      processes involved in the regulation of parasite abundance in the vertebrate
      host. Mathematical frameworks have been developed to explore the consequences of
      such processes in determining parasite population dynamics and the effect on
      these of control interventions. Post-control predictions are strongly influenced
      by the assumptions concerning the reproductive life span of the adult female worm
      (the longest-lived parasite stage) and the distribution of its survival times,
      and this notion is important to all frameworks. Here, we review the development
      of models concerning onchocerciasis and discuss the various approaches that have
      been used, presenting a deterministic framework with parameter values estimated
      from the Mexican onchocerciasis control programme. This model is used to evaluate
      interventions combining the removal of adult worms (nodulectomy) and the
      microfilaricidal and possibly sterilizing effect of ivermectin.

PMID- 11530356
TI  - The development of Malaria Early Warning Systems for Africa.
AB  - Current efforts to predict malaria epidemics focus on the role weather anomalies
      can play in epidemic prediction. Alongside weather monitoring and seasonal
      climate forecasts, epidemiological, social and environmental factors can also
      play a role in predicting the timing and severity of malaria epidemics. Such
      factors can be incorporated into a framework for malaria early warning.

PMID- 11530357
TI  - Genetic variability following selection of Haemonchus contortus with
      anthelmintics.
AB  - Genetic diversity in nematodes leads to variation in response to anthelmintics.
      Haemonchus contortus shows enormous genetic diversity, allowing anthelmintic
      resistance alleles to be rapidly selected. Anthelmintic resistance is now a
      widespread problem, especially in H. contortus. Here, I compare the genes
      involved in anthelmintic resistance in H. contortus with those that confer
      susceptibility or resistance on the free living nematode Caenorhabditis elegans.
      I also discuss the latest knowledge of genes associated with resistance to
      benzimidazoles, levamisole and the macrocyclic lactones and the need for DNA
      markers for anthelmintic resistance.

PMID- 11530359
TI  - The nursing shortage impacts the nursing profession as a whole.

PMID- 11530360
TI  - Fluids and electrolytes.

PMID- 11530361
TI  - Designing and creating a central venous catheter database and electronic charting
      system.
AB  - The delivery of efficient, quality, cost-effective care is essential in today's
      healthcare environment. Patients with central venous catheters (CVCs) constitute
      a large and growing population. A method is needed to track CVC status,
      associated problems, and management, leading to efficiency, cost containment, and
      improved patient outcomes. This article describes the process of creating a CVC
      database at a 232-bed, tertiary, pediatric care facility that serves a five-state
      geographical area in the intermountain west. This database converted an
      ineffective, labor-intensive, paper-based system for managing catheters to an
      electronic format. The CVC database offers relational reports, easily retrievable
      information at the point of patient contact, a complete progress note with key
      elements, and an alert system for adverse events and infections that can be used
      to follow up on and determine trends of CVC activity.

PMID- 11530362
TI  - Use of a protocol to minimize hypersensitivity reactions with asparaginase
      administration.
AB  - Several antineoplastic drugs in clinical use may cause hypersensitivity reactions
      (HSRs) that range from an occasional individual reaction to a significant HSR.
      Asparaginase preparations have a high incidence of invoking HSRs. The use of an
      HSR protocol may minimize symptoms experienced by the patient and ensure rapid
      implementation of life-saving measures when reactions occur. The article will
      define HSRs, review occurrences, and include a protocol developed to minimize
      reactions to asparaginase preparations.

PMID- 11530363
TI  - The necessity of routinely replacing peripheral intravenous catheters in
      hospitalized children. A review of the literature.
AB  - Insertion of a peripheral intravenous catheter can be a traumatic experience for
      a child. Current Centers for Disease Control and Prevention guidelines for adults
      recommend peripheral intravenous catheter replacement every 48 to 72 hours, but
      there are no pediatric recommendations. The rationale for changing catheters
      every 48 to 72 hours is to reduce the risk of complications such as phlebitis and
      infection. This article reviews literature on the use of peripheral intravenous
      catheters in the pediatric setting and will make a recommendation on replacement
      intervals.

PMID- 11530365
TI  - [Recent development of evaluation of the optic nerve head].

PMID- 11530364
TI  - Guidelines for the management of intravascular catheter-related infections.
AB  - These guidelines from the Infectious Diseases Society of America (IDSA), the
      American College of Critical Care Medicine (for the Society of Critical Care
      Medicine), and the Society for Healthcare Epidemiology of America contain
      recommendations for the management of adults and children with, and diagnosis of
      infections related to, peripheral and nontunneled central venous catheters
      (CVCs), pulmonary artery catheters, tunneled central catheters, and implantable
      devices. The guidelines, written for clinicians, contain IDSA evidence-based
      recommendations for assessment of the quality and strength of the data.
      Recommendations are presented according to the type of catheter, the infecting
      organism, and the associated complications. Intravascular catheter-related
      infections are a major cause of morbidity and mortality in the United States.
      Coagulase-negative staphylococci, Staphylococcus aureus, aerobic gram-negative
      bacilli, and Candida albicans most commonly cause catheter-related bloodstream
      infection. Management of catheter-related infection varies according to the type
      of catheter involved. After appropriate cultures of blood and catheter samples
      are done, empirical i.v. antimicrobial therapy should be initiated on the basis
      of clinical clues, the severity of the patient's acute illness, underlying
      disease, and the potential pathogen(s) involved. In most cases of nontunneled CVC
      related bacteremia and fungemia, the CVC should be removed. For management of
      bacteremia and fungemia from a tunneled catheter or implantable device, such as a
      port, the decision to remove the catheter or device should be based on the
      severity of the patient's illness, documentation that the vascular-access device
      is infected, assessment of the specific pathogen involved, and presence of
      complications, such as endocarditis, septic thrombosis, tunnel infection, or
      metastatic seeding. When a catheter-related infection is documented and a
      specific pathogen is identified, systemic antimicrobial therapy should be
      narrowed and consideration given for antibiotic lock therapy, if the CVC or
      implantable device is not removed. These guidelines address the issues related to
      the management of catheter-related bacteremia and associated complications.
      Separate guidelines will address specific issues related to the prevention of
      catheter-related infections. Performance indicators for the management of
      catheter-related infection are included at the end of the document. Because the
      pathogenesis of catheter-related infections is complicated, the virulence of the
      pathogens is variable, and the host factors have not been well defined, there is
      a notable absence of compelling clinical data to make firm recommendations for an
      individual patient. Therefore, the recommendations in these guidelines are
      intended to support, and not replace, good clinical judgment. Also, a section on
      selected, unresolved clinical issues that require further study and research has
      been included. There is an urgent need for large, well-designed clinical studies
      to delineate management strategies more effectively, which will improve clinical
      outcomes and save precious health care resources.

PMID- 11530366
TI  - [Electrical responses from the inner retina of rats with streptozotocin-induced
      early diabetes mellitus].
AB  - PURPOSE: To evaluate behavior of the scotopic threshold response (STR) and the
      oscillatory potential (OP) in the electroretinogram (ERG) in streptozotocin (STZ)
      induced diabetic rats (DM rats). METHODS: The amplitude of the STR and the OP 3,
      the implicit time of the STR, and the peak latency of the OP 3 of the DM rats
      were measured. RESULTS: No significant differences were observed in the mean
      amplitude or the mean implicit time of the STR between the control and the DM
      rats. On the other hand, the mean peak latency of OP 3 of the DM rats was
      significantly prolonged up to 125% of the control rats (p < 0.01), although there
      were no significant differences between the two groups in the mean OP 3
      amplitude. CONCLUSIONS: Although both STR and OP were of inner retinal origin,
      their behavior was different in DM rats. This result supported some reports
      describing how dopaminergic amacrine cells generate OP and glycinergic or
      GABAergic amacrine cells generate STR. In the early stage of diabetic
      retinopathy, there may be not only minor ischemia but also disorder of
      neurotransmission of the amacrine cells in the inner retinal layers.

PMID- 11530367
TI  - [Immunohistochemical study of interstitial keratitis in an animal model].
AB  - PURPOSE: We performed an immunohistochemical study on the development of
      interstitial keratitis in a rabbit model sensitized by ovalbumin (OA). METHODS: A
      mixture of OA (5 micrograms/ml) and Freund's complete adjuvant was initially
      injected subcutaneously (0.4 ml) into the rabbits' back and footpad (0.2 ml).
      After a week, the rabbits were sensitized by an injection of the same solution
      into the back (0.5 ml) again. After 4 weeks the rabbits underwent the same
      treatment as a booster shot. Then a week later OA solution (0.05 ml) was injected
      into the corneal stroma. We observed the cornea on days 1-3, 7, and 10 after the
      corneal treatment. Corneas on days 3 and 10 were examined by immunohistological
      methods using hematoxylin-eosin stain, methylgreen pyronin stain, and by
      immunohistochemical methods with anti-CD 4, anti-CD 8, and anti-OA antibodies.
      The localization of specific antibodies was identified by fluorescent-antigen
      method. Electron-microscopic observation was also done. RESULTS: Rabbits
      developed corneal opacity and edema on day 1, corneas had on immune ring with a
      peak intensity on day 3, and vascularization on day 7 after corneal treatment.
      Microscopic examination revealed infiltration of neutrophils in to the area of
      the immune ring on day 3 and many plasma cells at the limbus and stroma on day
      10. CD 4 positive cells were found at the limbus and stroma on days 3 and 10. CD
      8 positive cells were found at the limbus and stroma only on day 10. OA positive
      findings were observed at the immune ring and its inner area. In the fluorescent
      antigen method, specific antibodies were found in plasma cells at the limbus on
      days 3 and 10. CONCLUSIONS: In our experimental model of interstitial keratitis
      with immune ring and vascularization, the Arthus reaction was dominant.
      Infiltration of antigen specific plasma cells in the stroma with vascularization
      caused a modification of pathologic reaction in keratitis.

PMID- 11530368
TI  - [Evaluation of antiviral agents for adenovirus using the MTT method in vitro].
AB  - PURPOSE: Currently, there is no effective treatment for adenoviral
      conjunctivitis. We evaluated the antiviral inhibitory effect of four antiviral
      agents against adenovirus (ADV) in vitro. METHODS: Viruses used for the
      experiment were ADV type 4 (ADV 4), type 8 (ADV 8) and type 37 (ADV 37). We
      examined four antiviral agents, i.e., cidofovir (HPMPC), zalcitabine (ddC),
      foscarnet (PFA), and acyclovir (ACV). 50% effective concentration (EC50), 50%
      cytotoxic concentration (CC50) and selectivity index (SI) of compounds were
      determined for ADV infection in HEp-2 cells using the 3-(4,5-dimetylthiazol-2-yl)
      2,5-diphenyltetrazolium bromide (MTT) method. RESULTS: HPMPC and ddC showed an
      inhibitory effect against all three ADVs. In particular, ddC showed more potent
      and selective inhibition against ADV than HPMPC. PFA and ACV were ineffective
      against ADV. CONCLUSIONS: HPMPC and ddC were inhibitory against ADV 4, ADV 8 and
      ADV 37 replication in vitro. The MTT method is rapid and simple for the screening
      of antiviral agents. We think this method is also very useful for the screening
      of anti-ADV agents.

PMID- 11530369
TI  - [Factors related to initial success in macular hole surgery].
AB  - PURPOSE: To evaluate the factors of initial success in macular hole surgery.
      METHODS: This study included 526 eyes of 480 patients who underwent idiopathic
      macular hole surgery by one and the same surgeon. Surgical methods included
      conventional method (392 eyes), retinal pigment epithelium (RPE) scalping (61
      eyes), internal limiting membrane (ILM) removal (62 eyes), and RPE scalping
      combined with ILM removal (11 eyes). To evaluate the factors of initial success
      multiple regression was performed using the variables of (gender, age, stage,
      duration of symptoms, hole size, axial length, and preoperative visual acuity).
      RESULTS: The rate of initial success was 81.4% in all eyes, 80.9% in the
      conventional method, 78.7% in RPE scalping, 83.9% in ILM removal, and 100% in RPE
      scalping combined with ILM removal. Significant factors of initial success were
      as follows: gender (r = -0.091, p = 0.053), age (r = -0.14, p = 0.0062), duration
      of symptoms (r = -0.23, p < 0.0001), hole size (r = -0.23, p < 0.0001), and axial
      length (r = -0.21, p < 0.0001) in the conventional method, hole size (r = -0.56,
      p = 0.0006) in ILM removal and stage (r = -0.43, p = 0.0011) and preoperative
      visual acuity (r = 0.30, p = 0.018) in RPE scalping. CONCLUSIONS: Significant
      factors of initial success were being male being young, shorter duration of
      symptoms, smaller hole size, and shorter axial length in the conventional method,
      smaller hole size in ILM removal and stage 4 and better preoperative visual
      acuity in RPE scalping method.

PMID- 11530370
TI  - [The effect of attention on visual evoked potentials elicited by a newly designed
      stereogram].
AB  - PURPOSE: To investigate whether the visual evoked potentials (VEPs) obtained by a
      newly designed stereogram were generated by some higher function like depth
      perception, we examined the effect of attention on the VEPs. SUBJECTS AND METHOD:
      Eight subjects participated in the experiments. The VEPs were recorded according
      to the international 10/20 system. The stimulus consisted of circles with or
      without disparity presented on 4 locations around the fixation point, and they
      appeared in one of 3 patterns in random order when viewed through red/green
      spectacles 1. at the same distance as the fixation point, 2. in front of it, or
      3. at the back of it. The near pattern was defined as the target. In Experiment
      1, the subjects just fixated on the fixation point. In Experiments 2 and 3, they
      were required to respond to the target by pressing a button and counting the
      number (target discrimination task). RESULTS: A scalp negative potential with a
      latency of 170-280 msec was elicited in the lateral occipital area. For each of
      the 3 patterns the amplitude was greater in Experiments 2 and 3 than in
      Experiment 1. In Experiments 2 and 3, stimuli with disparity resulted in larger
      amplitude than without disparity. The target stimulus also evoked larger
      potentials than non-target stimuli did, although no such effect was apparent in
      Experiment 1. CONCLUSION: Attention, as well as disparity, increased the VEPs
      amplitude, which indicates that the potential could be generated by neural
      activity higher than V 1 including depth perception. Moreover, the potential
      showed characteristics similar to attention-related potentials modulated by visuo
      spatial attention.

PMID- 11530371
TI  - [Hyperfluorescent areas observed in late-phase indocyanine green angiography (IA)
      of IA findings in fellow eyes of unilateral age-related macular degeneration].
AB  - PURPOSE: To evaluate abnormal findings of indocyanine green angiography (IA),
      predisposing to exudative age-related macular degeneration (AMD) in fellow eyes
      of unilateral exudative AMD. METHODS: We categorized 83 fellow eyes of unilateral
      exudative AMD into two groups, i.e. 55 eyes with early age-related maculopathy,
      and 28 eyes with normal aging. We performed IA. RESULTS: The late phase of IA
      demonstrated hyperfluorescent areas in 27 of the 83 fellow eyes, which included
      22 of the 55 eyes with early age-related maculopathy and five eyes of 28 eyes
      with normal aging. The prevalence of the late-phase hyperfluorescence was
      statistically significant in early age-related maculopathy. Eight of the 22 eyes
      with early age-related maculopathy and one of the five eyes with normal aging
      progressed to exudative AMD. CONCLUSIONS: Hyperfluorescent areas observed in late
      phase IA before the manifestation of exudative AMD suggested the possible
      presence of choroidal neovascular membrane in the subretinal pigment epithelial
      space.

PMID- 11530373
TI  - [Clinical features of idiopathic macular holes].
AB  - PURPOSE: The purpose of this study was to evaluate the clinical features of
      idiopathic macular holes. MATERIALS AND METHODS: The clinical features were
      examined in consequentive 526 eyes of 480 patients with idiopathic macular hole
      who underwent vitrectomy. RESULTS: Sixty-seven% of the patients were female. The
      mean onset age was 64.4 years of age and 60% of the cases were in their 60's at
      the time of onset. The mean refractive value was -0.66 dioptor and 40% of the
      cases were emmetropia with a refractive value between -1.0 dioptor and +1.0
      dioptor. The onset age was positively correlated with refractive value. The
      visual acuity was negatively correlated with onset age, duration after onset, and
      the size of the macular hole. The duration was positively correlated with onset
      age. The size of the macular hole was positively correlated with age and
      duration. The factors for good visual acuity were determined by bilaterality,
      youth, or small size. Also we found the factors for large size of macular holes
      to be female gender, long duration of the hole, being in stage 4, and low visual
      acuity. CONCLUSIONS: The incidence of idiopathic macular hole is seen more in
      eyes of patients in their 60's and in emmetropic eyes. Patients with myopic eyes
      tend to have younger onset. The size of the macular hole in females tends to be
      larger than in males.

PMID- 11530372
TI  - [Results of therapy for orbital malignant lymphoma].
AB  - PURPOSE: To elucidate the clinical and histopathological features of orbital
      malignant lymphoma, and to develop a protocol for effective treatment. MATERIALS
      AND METHODS: The present study analyzed 18 cases of orbital lymphoma which were
      treated at Yamagata University Hospital over the last 14 years. The tentative
      strategy for choosing the treatment was to treat the cases of clinical stage I
      (Ann Arbor criteria) with curative intent and the cases of stage II-IV with
      palliative intent. RESULTS: Six patients had primary orbital lymphomas, 2 had
      secondary orbital lymphomas, and 10 had metastatic orbital lymphomas.
      Histopathologically, all the cases of primary lymphoma were of low-grade
      malignancy and all the cases of secondary lymphoma were of intermediate-grade
      malignancy. Of the metastatic lymphoma cases, 3 were of low-grade and 7 of
      intermediate-grade malignancy. The cases of primary lymphoma were Stage I and
      were treated by radiation or chemotherapy. The cases with secondary lymphoma were
      Stage II and were treated by both radiation and chemotherapy. The cases with
      metastatic lymphoma were Stage III or IV and were treated by chemotherapy and/or
      radiation. Control of orbital lymphoma was achieved in all 6 cases with primary
      lymphomas. Although the survival rate was 0% for secondary lymphomas and 50% for
      metastatic lymphomas, ocular complications were improved during the remainder of
      the patients' life. CONCLUSIONS: All the primary orbital lymphomas were treated
      effectively by radiation or chemotherapy. For secondary and metastatic orbital
      lymphoma, our strategy for treatment was beneficial by improving ocular
      complications and the quality of life.

PMID- 11530374
TI  - [Clinical evaluation of the Heidelberg Retina Tomograph II].
AB  - PURPOSE: To evaluate the usefulness of Heidelberg Retina Tomograph (HRT) II
      prototype, which is an easily handled model for routine optic disc examination in
      glaucoma clinics. METHODS: Ten eyes of 10 normal volunteers and 18 eyes of 18
      open-angle glaucoma patients followed at Gifu University were studied. The
      reproducibility of three consecutive optic disc measurements with a 15 degrees x
      15 degrees field using HRT II and with a 10 degrees x 10 degrees field using HRT
      (version 2.01) were evaluated by the same examiner on the same day. We also
      examined the correlation of the main topographic parameters (disc area, cup area,
      cup/disc area ratio, rim area, cup volume, rim volume, cup shape measure) between
      HRT II and HRT. RESULTS: The mean (+/- standard deviation) reproducibility of
      optic disc measurements with HRT II and HRT were 17.5 +/- 7.6 microns and 19.3 +/
      9.6 microns, respectively. This difference was not significant. All topographic
      parameters obtained from HRT II and HRT (R = 0.86-0.98, p < 0.01) showed
      statistically significant correlations with each other. CONCLUSION: The HRT II
      has high reproducibility of measurements and reliable stereometric parameters
      comparable to the conventional HRT.

PMID- 11530376
TI  - [Brain function and local anatomy for SPM analysis].
AB  - The local brain function has been traditionally investigated based on the
      correlation of dysfunction with sites of brain lesions. The investigation of
      relationships between brain function and brain anatomy in both normal subjects
      and cooperative patients is now a reality through the advent of noninvasive brain
      monitoring techniques such as positron emission tomography using 15O-water and
      functional magnetic resonance imaging. While the development of those hardwares
      is taken for granted, it is quite necessary to deal with large amount of image
      data in a statistically accurate and rapid manner. Statistical parametric mapping
      (SPM) developed by Friston et al., is a standard method processing the image data
      in activation studies and now available world-wide. SPM can analyze multiple
      brains and display the activated site on the standard brain which is settled on
      Talairach's atlas in SPM95 and on MNI (Montreal Neurological Institute) template
      in SPM96 and SPM99. In activation study, it is most important to design the tasks
      that specifically enable the local brain areas to be active and elucidate the
      unknown local function. Thus we must realize in detail what has been known and
      not about local brain function.

PMID- 11530375
TI  - [Indium-111-oxine labeled platelet and leucocyte scintigraphy for diagnosis of
      thrombi and inflammation].
AB  - There were many studies for diagnosis of localization and activity of thrombi and
      inflammation using indium-111-oxine labeled platelet (In-plt) and leucocyte
      scintigraphy (In-WBC), respectively. The study using these techniques is
      decreasing recently, because other diagnostic modarities have been developed and
      the techniques of these scintigraphy are complicated. However, because these
      scintigraphy are noninvasive, it is expected that these are widely applied to the
      clinical diagnosis and follow up. 1. Platelet scintigraphy can visualized thrombi
      and distinguish the activation of platelet aggregation. There were many reports
      and reviews. I reviewed recent studies in cardiovascular diseases and our cases.
      2. Leucocyte scintigraphy (In-WBC) is usually used for the detection of
      inflammation. Furthermore, it is possible that In-WBC can detect inflammation of
      the arteriosclerotic lesion of the aortic wall. I introduced our studies of In
      WBC in aortic aneurysma and aortic dissection. The In-WBC maybe useful for
      detection of inflammation of the aortic aneurysma and evaluation of prognosis of
      aortic dissection.

PMID- 11530377
TI  - [Clinical application of gated SPECT imaging to regional function assessment:
      current status and limitations].
AB  - It is likely that clinical applications of ECG-gated single-photon emission
      computed tomography (SPECT) are established in nuclear cardiology practice
      because of the improved diagnostic accuracy of gated SPECT imaging for the
      detection of coronary artery disease and because this technique enables not only
      simultaneous assessment of myocardial perfusion and function but also improvement
      of risk stratification of coronary patients. Although a gated approach with SPECT
      imaging has been demonstrated to have high reproducibility and reliability for
      quantifying global function, there are several limitations in appropriate
      processing of 4-dimensional data for quantitative assessment of regional
      function. Even if limited spatial and temporal resolutions and a lack of
      attenuation and scatter corrections are disregarded, sufficient data collection,
      image-quality control, and precise application of algorithms to gated SPECT data
      are prerequisite. The results of several kinds of quantitative analysis of
      regional cardiac function, such as regional wall motion (distance deviation of
      the inner myocardial border), regional ejection fraction, percent wall
      thickening, and percent count increase with or without self-normalization have
      been reported. Further clinical application of quantitative regional function
      assessment by a gated SPECT technique, however, requires standardization of data
      acquisition, data analysis, and data presentation with appropriate quantitative
      parameters; production of a standard map using quantitative values; and
      validation study by comparison with results of visual analysis and other
      modalities in a large-scale patient population.

PMID- 11530378
TI  - [Contrast enhancement for sentinel lymph node imaging].
AB  - The paper proposes a new contrast enhancement method for sentinel lymph node
      imaging. The sentinel lymph node image acquired by a conventional gamma camera
      system has a wide dynamic range, so that the contrast of sentinel lymph nodes
      relatively decreases. The proposed method, which is named an annular background
      subtraction (ABS) method, first found the center of the distribution of activity.
      Then we calculated the mean value in each annular area centered at the injection
      point of radiopharmaceuticals with one pixel width. The original image was
      subtracted by the mean value at each annular area. The performance of the
      proposed method was confirmed by clinical data.

PMID- 11530379
TI  - [Assessment of myocardial damage and metabolic disorder in the left ventricle in
      patients with mitral stenosis using 201Tl and 123I-BMIPP myocardial SPECT].
AB  - This study was designed to evaluate the myocardial damage and metabolic disorder
      of the left ventricle in patients with mitral stenosis. We studied 15 patients
      with mitral stenosis. Their grade of chronic heart failure using New York Heart
      Association classification were class I: 5 patients, class II: 5, class III: 3,
      class IV: 2, respectively. The severely stenotic group (valve area < 1.5 cm2)
      included 6 patients, mildly stenotic group (1.5 cm2 < or = valve area < 2.5 cm2)
      included 9. A 111 MBq of 123I-BMIPP was intravenously injected at rest, SPECT
      images were obtained at 15 min and 3 hours after injection. A 111 MBq of 201Tl
      was intravenously injected at rest, and SPECT images were obtained at 15 min
      after injection. Washout rate (WR) of 123I-BMIPP from the whole left ventricle
      was obtained using polar maps. The concentration of norepinephrine (NE: pg/ml) in
      the blood at rest was measured. The mean values of pulmonary artery pressure was
      measured in ten patients using Swan-Ganz catheter. 123I-BMIPP myocardial SPECT
      and measurement of NE were reexamined in 5 patients after mitral valvuloplasty.
      NE values were 476 +/- 72 and 793 +/- 286 in classes I + II and III + IV,
      respectively. NE values was increased in the severe heart failure group (p <
      0.05). NE values were 480 +/- 69 and 743 +/- 295 in the mildly and severely
      stenotic groups, respectively. NE value was increased in severely stenotic group
      (p < 0.05). Twelve patients showed normal uptake on both 201Tl and 123I-BMIPP
      myocardial SPECT. Three patients showed slightly reduced uptake on both 201Tl and
      123I-BMIPP myocardial SPECT. WR was 27.2 +/- 4.8% and 44.3 +/- 6.7% in class I +
      II and class III + IV, respectively. WR was increased in severe heart failure
      group (p < 0.05). WR was 27.8 +/- 6.0% and 41.3 +/- 9.4% in the mildly and
      severely stenotic group, respectively. WR was increased in the severely stenotic
      group (p < 0.05). NE was correlated with WR (p < 0.001). In patients with mitral
      valvuloplasty, WR was 44.3 +/- 6.7% and 31.4 +/- 4.7% before and after mitral
      valvuloplasty, respectively. NE values were 857 +/- 266 and 574 +/- 165,
      respectively. Both WR and NE were decreased after mitral valvuloplasty (p <
      0.01). In patients with mitral stenosis, WR was increased in the severe heart
      failure group and severely stenotic group without apparent myocardial damage.
      Myocardial metabolism in the left ventricle might be influenced by right heart
      failure through, for example, NE and neurohormonal factors.

PMID- 11530380
TI  - [Biodistribution of hypoxic marker, 99mTc-HL91 (4,9-diaza-3,3,10,10
      tetramethyldodecan-2,11-dione dioxime)].
AB  - 99mTc-HL91 (4,9-diaza-3,3,10,10-tetramethyldodecan-2,11-dione dioxime) was
      developed as a hypoxic marker. Athymic mice bearing human tumors were
      administered with 99mTc-HL91 to evaluate it from the clinical point view. The
      tumor was visualized clearly 4 hours after injection. The biodistribution study
      revealed that 99mTc-HL91 was accumulated in the liver (tissue-to-blood ratio
      (T/B) = 11.5) and kidney (2.25) with higher than in the tumor (1.01). Oxygen
      condition of the tumor and muscle was measured by using the probe. 99mTc-HL91
      uptake of tumors with PO2 (tumor-to-muscle ratio) under 0.55 was higher than that
      with 0.55 or higher PO2. Oxygen condition of tumors with 1.0 or higher uptake
      (tumor-to-blood ratio) was lower than that with the lower uptake. Autoradiography
      of tumor sections indicated that 99mTc-HL91 was scarcely accumulated in the
      necrotic and viable areas while strong radioactivity was observed in the border
      zone (speculated to be hypoxic condition). Our experimental results suggest that
      the 99mTc-HL91 scintigraphy may be useful for evaluating oxygenation status of
      some tumors in non-abdominal region.

PMID- 11530381
TI  - [Comparison of 133Xe gas dynamic SPECT and thin-section CT in patients with
      pulmonary emphysema].
AB  - PURPOSE: We assessed 133Xe gas dynamic single photon emission computed tomography
      (SPECT) by comparing washout axial images with thin-section CT (TSCT) in patients
      with pulmonary emphysema. METHODS: Twenty-three patients were studied. All
      patients were diagnosed as having pulmonary emphysema on the basis of TSCT. We
      compared TSCT of upper, middle and lower lung fields with 133Xe gas dynamic SPECT
      axial images at the corresponding levels during the 3 to 4 minutes of washout
      phase. If the degree of 133Xe gas retention or TSCT finding of ventral and dorsal
      parts was not the same, the images were divided into two parts. RESULTS: A total
      of 174 lesions in 23 cases were examined, but 3 lesions having no retention of
      133Xe gas at equilibrium phase were excluded. The results showed that: there were
      37 lesions (21.6%) with equivalent severity on both images; there were 42 lesions
      (24.5%) with more severity on 133Xe gas dynamic SPECT than on TSCT; and there
      were 92 lesions (53.8%) with more severity on TSCT than on 133Xe gas dynamic
      SPECT. The severity on 133Xe gas dynamic SPECT and TSCT was not always
      compatible. One of the reasons for the variable 133Xe gas retention even when the
      lesion had the same severity on TSCT, may be bronchial stricture which cannot be
      seen on TSCT. CONCLUSION: By comparison of axial images of 133Xe gas dynamic
      SPECT with CT images, we could recognize the areas of 133Xe gas retention in
      detail. Results suggest that 133Xe gas dynamic SPECT can be useful to identify
      ventilation impairment in pulmonary emphysema.

PMID- 11530382
TI  - [Experience of gamma-detecting probe for the survey of sentinel node in
      gastroesophageal malignancies].
AB  - Gamma-detecting probe NAVIGATOR GPS (Autosuture Japan) was evaluated by using of
      99mTc. Linearlity of counting in radioactivity was fairly good, but the
      sensitivity of the prove is so low, that sentinel node (SN) should contain the
      3.7 x 10(-3) MBq (0.1 microCi) of 99mTc or more for the most effective use of it.
      And the count rate of the gamma-detecting probe was influenced by the distance
      and angle from the 99mTc source variously. It is important for the operator to
      know such characteristics of the gamma-detecting probe in order to obtain the
      correct SN judging.

PMID- 11530383
TI  - [Evaluation of efficiency of a multi-crystal scintillation camera Digirad 2020tc
      Imager using a solid-state detectors].
AB  - Digirad 2020tc Imager is the movable scintillation camera, consisting of
      combining multi-crystal scintillators (CsI(Tl)) and photo-diodes. Total numbers
      of element are 4096, which are further divided into 16 x 16 modules. Each module
      contains 4 x 4 elements. We have examined Digirad 2020tc according to NEMA
      (National Electrical Manufactures Association), and the following results are
      obtained; the maximum count rate; 221 kcps, total system uniformity; 1.3%
      (integral uniformity), 0.9% (differential uniformity), system spatial resolution;
      6.97 +/- 0.72 mm (the LEHR collimator to 99mTc source at 10 cm), intrinsic energy
      resolution; 12.8%, total system sensitivity; 3270.8 cpm/MBq (with LEHR collimator
      using 99mTc source at 10 cm). Further more, we determined the contrast of an
      imaging using the pin-hole (100 microns phi) 99mTc source in order to know the
      signal per noise (S/N) ratio among the pixels (S/N; 93.4 +/- 46.2 (first
      pixels)). Although the physical dimension of the camera has a smaller field of
      view, comparing with the standard camera, Digirad 2020tc has the equivalent
      characteristics as well as that of the standard camera and its field view is
      enough to measure the adult lung perfusion using a diverging collimator. We will
      further examine Digirad 2020tc with its movable portability and expect
      applications in nuclear medicine.

PMID- 11530384
TI  - [Plasma (1-->3)-beta-D-glucan level in allergic bronchopulmonary aspergillosis].
AB  - We measured the plasma (1-->3)-beta-D-glucan (beta-DG) levels in patients with
      allergic bronchopulmonary aspergillosis (ABPA) and compared their temporal
      changes with those of serum IgE and eosinophil counts in the peripheral blood.
      The subjects were three ABPA patients who were newly diagnosed or had had a
      relapse between May 1998 and April 1999. Before treatment, all three cases showed
      high plasma beta-DG values, which declined following corticosteroid treatment
      with or without oral itraconazole. In two cases, the beta-DG values rose again on
      relapse. beta-DG values showed a tendency to change in parallel with IgE,
      although they moved in the opposite direction after a relapse in one case. The
      present findings suggest that the plasma beta-DG level may be a useful follow-up
      indicator of the infectious aspect of this disease.

PMID- 11530385
TI  - [Lack of knowledge about smoking-related risks for diseases in the general public
      in Japan].
AB  - Cigarette smoking is the primary preventable cause of various diseases and death.
      Smoking has been causally related to lung cancer, other malignancies,
      atherosclerosis, coronary heart disease, and chronic obstructive pulmonary
      disease. There have been few studies, however, of whether the ordinary citizen in
      Japan understand the risks of serious diseases caused by smoking. Four hundred
      and thirty six people attended a seminar of respiratory diseases entitled
      "Cigarette smoking and lung cancer; prevention and treatment of asthma; senile
      care and prevention of pneumonia". After the seminar, unsigned questionnaires
      were filled out by 403 of those in attendance. Three hundred eighty nine (165
      males and 224 females) respondents correctly answered the questionnaires, and
      these were analyzed in the study. Attendants comprised 243 who had never smoked
      (63%), 99 former smokers (25%), and 39 current smokers (10%). Three hundred forty
      seven attendants (89%) answered that smoking is harmful to the health, and 371
      (95%) that it is causally related to lung cancer. In contrast, lower numbers of
      attendants answered that smoking is causally related to other diseases: pulmonary
      emphysema, 65% of the responses; chronic bronchitis, 68%; laryngeal cancer, 77%;
      myocardial infarction, 53%; and atherosclerosis, 49%. Of the 39 current smokers,
      27 answered that they would stop smoking after the seminar. Although many people
      partly understand the risks of smoking, they do not have a clear knowledge of the
      risks of diseases besides lung cancer. Education about the risks of smoking and
      about smoking cessation is required.

PMID- 11530386
TI  - [Effect of FP inhalation and airway inflammation assessed by ECP in asthma].
AB  - We studied the effects of fluticasone propionate (FP) inhalation and the airway
      inflammation in beclomethasone dipropionate (BDP)-resistant bronchial asthma.
      Twenty-five patients who had used BDP and whose mean PEF was less then 80% were
      enrolled in this study. After 2 weeks of BDP inhalation. FP inhalation was
      administered. The total eosinophil count in the peripheral blood (/microliter),
      their percentage of the total WBC count (% Eos), the count in induced sputum, the
      serum ECP content and the induced sputum ECP content were measured before and
      after 6 weeks of FP treatment. There was a significant increase of morning and
      evening PEF, from 63.1% to 76.1% and from 63.6% to 76.2%, respectively. There was
      a significant positive correlation between the peripheral blood % Eos and the %
      increase of PEF (p < 0.01). There was also a significant positive correlation
      between the induced sputum % Eos and the % increase of PEF (p < 0.05). The
      induced sputum ECP content was still as high as 180 micrograms/l after FP
      treatment. The mean % PEF did not reach 80% after FP treatment. This study
      suggests that airway inflammation persists in some severe asthma patients despite
      inhalation of FP 800 micrograms.

PMID- 11530387
TI  - [A case of bronchioloalveolar cell carcinoma with bilateral diffuse interstitial
      infiltrative shadow during the treatment of Takatsuki's disease].
AB  - A 54-year old man treated with Takatsuki's disease was referred to us complaining
      of cough and excessive sputum. A chest roentgenogram showed bilateral diffuse
      interstitial infiltrative shadow. Chest CT showed banding shadows around the
      bronchioles and lobule-septum thickening in the right middle and both lower lung
      fields, and many small nodules in both lower lung fields. The histological
      diagnosis was adenocarcinoma replaced with one layer of bronchiolar epithelium,
      and partly bronchiolo-alveolar carcinoma. The patient received 3 courses of
      combination chemotherapy with docetaxel and cisplatin. After chemotherapy, the
      chest CT showed no change. The clinicopathological characteristics of this rare
      case included adenocarcinoma mixed with bronchioloalveolar carcinoma, in which
      radiography showed bilateral diffuse interstitial infiltrative shadow.

PMID- 11530388
TI  - [A case of pneumonia, septic pulmonary embolisms with cavities, bilateral large
      lung abscesses, and multiple liver abscesses caused by Klebsiella pneumoniae].
AB  - A 64-year-old man suffering from diabetic hyperosmolar non-ketotic coma was
      admitted for acute lung abscess in the left apical lung field. Sputum culture and
      blood culture showed a heavy growth of Klebsiella pneumoniae (K. pneumoniae). He
      was suffering from sepsis, septic pulmonary embolisms with cavities, bilateral
      pulmonary consolidations, and multiple liver abscesses. Gradually, the bilateral
      lung consolidations resolved and areas of consolidation were noted to undergo
      extensive cavitation bilaterally. Cavitation and abscess formation are frequent
      complications of K. pneumoniae. Generally, large bilateral lung abscesses caused
      by K. pneumoniae have a poor prognosis. Cavity nodules are often present in
      septic pulmonary embolisms. We report a very rare case in a patient with three
      types of cavities with differing mechanisms. The first was an acute lung abscess,
      the second, septic pulmonary embolisms with cavities, and the third, large
      bilateral lung cavities noted in the course of resolving consolidations.

PMID- 11530389
TI  - [A case of Churg-Strauss syndrome in which positive rheumatoid factor and MPO
      ANCA preceded the development of clinical symptoms of vasculitis].
AB  - A 52-year-old man in whom bronchial asthma had been diagnosed in 1995 was
      admitted for the treatment of Churg-Strauss syndrome in June 1997. Positive tests
      MPO-ANCA and rheumatoid factor preceded the symptoms of vasculitis for several
      months. A skin biopsy revealed infiltration of eosinophils in the vessel walls,
      and the diagnosis of Churg-Strauss syndrome was confirmed. After systemic
      administration of corticosteroids, the symptoms other than mononeuritis improved
      markedly, and his MPO-ANCA and rheumatoid factor became negative. Rheumatoid
      factor and MPO-ANCA may be useful for the early diagnosis of Churg-Strauss
      syndrome in patients with bronchial asthma in which a well-controlled disease
      develops into an intractable condition.

PMID- 11530390
TI  - [Five cases of lung cancer with emphysematous bullae].
AB  - In bullous lung disease the incidence of lung cancer occurs with significant
      frequency among the general population, but lung cancer with a spontaneous
      pneumothorax is rare, and the prognosis is frequently poor. Five cases of lung
      cancer with emphysematous bullae of the lung were reported. In 4 cases there were
      simultaneous occurrences of lung cancer and pneumothorax. The patients were 49-,
      36- and 68-year-old men and a 72-year-old woman, and the initial sign in all was
      pneumothorax. Histologically, there was one squamous cell carcinoma, two poorly
      differentiated adenocarcinomas and one well-differentiated adenocarcinoma. In the
      other case, giant emphysematous bullae were diagnosed in a 51-year-old man and
      were treated by bullectomy. Histological examination incidentally revealed a
      small well-differentiated adenocarcinoma, which extended along the wall of the
      largest right bulla. About 18 months later, the patient was found to have poorly
      differentiated adenocarcinoma of the left lung, which was treated surgically. We
      should always be careful of lung cancer associated with emphysematous bullae and
      pneumothorax.

PMID- 11530391
TI  - [Severe Klebsiella pneumonia improved by endotoxin adsorption and continuous
      hemodiafiltration].
AB  - A 57-year-old man who had past history of alcoholic hepatitis was admitted to our
      hospital because of fever, general malaise and dyspnea. Chest X-ray films and
      computed tomographic scans disclosed lobar pneumonia of the right upper lobe.
      Laboratory tests showed hypoxemia and renal dysfunction. Artificial ventilation,
      endotoxin adsorption (PMX) and continuous hemodiafiltration (CHDF) were started
      on the day after admission because of the appearance of progressive renal
      failure, hypotension and disturbance of consciousness. A diagnosis of septic
      multiple organ failure was made on the basis of a blood and sputum culture that
      revealed a K. pneumoniae infection. After the initiation of intensive therapy,
      the patient's general condition improved and artificial ventilation, PMX and CHDF
      were withdrawn. However, MRSA was isolated from sputum specimens and a lung
      abscess developed. In spite of vancomycin administration, the effect was limited.
      The patient underwent a right upper lobectomy and was discharged. The prognosis
      of bacteremic K. pneumoniae pneumonia in alcoholics is reported to be very poor.
      In our case, it is suggested that PMX and CHDF contributed to the improvement of
      the clinical course.

PMID- 11530392
TI  - [Mycoplasma pneumonia complicated by acute renal failure].
AB  - A 17-year-old woman presented with cough and fever. Treatment with cefteram
      pivoxil and fosfomycin calcium was not effective. Chest radiography showed
      infiltration with an air bronchogram in the left upper lung field. The case was
      initially treated as atypical pneumonia by administering minocycline
      hydrochloride and piperacillin sodium. Since acute renal failure progressed
      rapidly, we introduced hemodialysis, and renal function improved. The mycoplasma
      polymerase chain reaction (PCR) in the pharynx smear was positive, and the
      mycoplasma serum titer was 1280 on admission. On the basis of these findings,
      mycoplasma pneumonia was diagnosed. Only one other case of mycoplasma pneumonia
      with hemodialysis has been reported in Japan. We report and assess the
      pathogenesis of mycoplasma pneumonia complicated by renal dysfunction.

PMID- 11530393
TI  - [Multiple cavitary pulmonary metastases from ovarian cancer: a case report].
AB  - Cavitation in pulmonary metastases is thought to be uncommon. To date, few cases
      of pulmonary metastases originating from ovarian cancer and showing cavitation
      have been reported. We report a patient with multiple cavitation in pulmonary
      metastases from ovarian mucinous cystadenocarcinoma. A 28-year-old woman was
      admitted to our hospital presenting with cough and fever. The patient had
      undergone right ovariectomy for ovarian mucinous cystadenocarcinoma at the age of
      23 years. Her chest radiograph on admission showed multiple cavities associated
      with infiltration in both lungs. Histological sections obtained by transbronchial
      lung biopsy revealed mucus-secreting adenocarcinoma, and a diagnosis of
      metastatic lung cancer from the ovary was made. Computed tomographic (CT) scans
      of the chest demonstrated various findings, including multiple thick-walled
      cavities, thin-walled cavities, air-space consolidations, ground glass opacities,
      and centrilobular nodular shadows formed by aspiration of the mucinous
      secretions. It is important to recognize that cavitation can occur in pulmonary
      metastases from ovarian cancer.

PMID- 11530394
TI  - [Three cases of small intrapulmonary lymph nodes coincidental with primary lung
      cancer].
AB  - We report three cases of intrapulmonary lymph nodes coincidental with primary
      lung cancers. In the first case, a 56-year-old man had a small subpleural nodule
      in the right lower lobe associated with adenocarcinoma of the right upper lobe.
      The small nodule was 10 mm in diameter and was difficult to differentiate
      radiologically from intrapulmonary metastasis. Wedge resection of this small
      nodule was performed. Histologic examination of the nodule revealed an
      intrapulmonary lymph node with anthracotic pigmentation. A right upper lobectomy
      for adenocarcinoma was performed, and was completely curative. The second
      patient, a 77-year-old woman, had adenocarcinoma in the right lower lobe
      diagnosed by transbronchial biopsy. Computed tomography (CT) revealed a small
      nodule 5 mm in diameter in the right upper lobe. Histologic examination of the
      small wedge-resected nodule revealed a lymph node. Lower lobectomy was performed
      with completely curative results. In the third case, a 63-year-old man was
      admitted for investigation of a mass shadow in the right upper lobe. CT showed a
      small nodular shadow in the right middle lobe, confirmed histologically to be
      lymphoid tissue, in addition to the original mass, which was diagnosed by
      transbronchial biopsy as squamous cell carcinoma. Upper lobectomy was performed
      and proved to be curative. Small intrapulmonary lymph nodes are very difficult to
      diagnose by methods other than surgical resection. When a small intrapulmonary
      nodule is detected in a patient with primary lung cancer, the presence of an
      intrapulmonary lymph node must be considered. If radiological characters
      compatible with an intrapulmonary lymph node are found and there is no other
      metastasis indicating poor prognosis, it should be considered as a possible
      indication for surgical resection.

PMID- 11530395
TI  - [Induction of psoriasis by human recombinant granulocyte colony stimulating
      factor in a patient with small cell lung cancer].
AB  - A 70-year-old man with small cell lung cancer was admitted to our hospital. He
      received chemotherapy consisting of cisplatin plus etoposide with concurrent
      chest irradiation. Because the patient had leukocytopenia after the first course
      of chemotherapy, he was treated subcutaneously with filgrastim (human recombinant
      granulocyte colony stimulating factor, G-CSF). Three days later, he developed
      psoriasiform skin eruptions mainly on the surface of the chest radiation field.
      When filgrastim was replaced with lenograstim (G-CSF), the skin lesions improved.
      But, after a second course of chemotherapy, lenograstim caused generalized
      psoriasiform eruptions. The patient had no previous history of psoriasis or any
      pre-existing skin disease. A skin biopsy revealed a Munro microabscess and
      spongiform pustules of Kogoj, which are the findings characteristic of the
      pathology of psoriasis. The MEDLINE report search has revealed, this is the first
      report of induction of psoriasis by G-CSF in a patient with small cell lung
      cancer.

PMID- 11530396
TI  - [A case of pneumonitis possibly due to isocyanate associated with high levels of
      serum KL-6].
AB  - A 47-year-old automobile painter developed dry cough, chills and dyspnea after
      four months of painting work. The spray contained isocyanates (HDI). A chest
      radiograph showed bilateral ground-glass shadows. The serum KL-6 level was very
      high: 11,100 U/ml. Marked lymphocytosis and a striking decrease in the CD4/CD8
      ratio were observed in the bronchoalveolar lavage fluid. Transbronchial lung
      biopsy specimens showed alveolitis and bronchiolitis. Cessation of exposure to
      isocyanates improved the symptoms and laboratory data. We suspected that the
      patient was suffering from hypersensitivity pneumonitis induced by isocyanates.
      Specific IgG antibodies for TDI, MDI, and HDI were not demonstrated by enzyme
      linked immunosorbent assay. Because abnormal shadows in the chest radiograph did
      not improve quickly after admission, we administered glucocorticoids which
      improved the symptoms, the chest radiograph findings, and the serum KL-6 level.

PMID- 11530397
TI  - [A case of Coxiella burnetii pneumonia in an adult].
AB  - A 49-year-old man visited our hospital complaining of a continuous high-grade
      fever and cough which had appeared during his stay in Indonesia. He was admitted
      on the same day because his laboratory data showed marked inflammatory changes
      and his chest radiograph revealed an infiltrative shadow in the right upper lung
      field. Initial treatment with beta-lactams was not effective and both his
      symptoms and his chest radiograph worsened. However, treatment with erythromycin
      clearly had an effect. Then, we carried out several tests for detection of
      atypical pathogens including Mycoplasma and Chlamydia. Finally, the case was
      diagnosed as one of Coxiella burnetii pneumonia because the DNA of C. burnetii
      was detected from his sera and seroconversion of C. burnetii--specific antibody
      was observed among paired serum samples. C. burnetii is one of the most commonly
      recognized pathogens among community-acquired pneumonias in Western countries,
      but in Japan, reports of community-acquired C. burnetii pneumonia have been rare.
      This difference may be due to the features of Q fever, in which there are large
      differences in frequency and form from country to country and among areas of the
      same country. Surveillance of C. burnetii pneumonia in Japan and different area
      will be required.

PMID- 11530398
TI  - Tuberculosis. Scientific blueprint for tuberculosis drug development.
AB  - The Global Alliance for TB Drug Development is dedicated to closing the R&D gaps.
      However, advances cannot be made without investment by national and international
      health organizations, private sector pharmaceutical and biotechnology firms,
      foundations, and others. Their support is needed to develop a broad portfolio of
      promising candidates with a special emphasis on developing fast-track and/or
      sterilizing drugs. Funding agencies and research organizations must devote
      significant resources in the short term to close the gaps in the R&D value chain
      and to leverage the strengths available. Fortunately, the need, the expertise,
      and the enthusiasm exist. By combining resources into R&D efforts to discover and
      develop a broad portfolio of promising candidates, the Global Alliance and its
      sponsors can make a vitally important contribution to improved control and the
      eventual elimination of tuberculosis from every country of the world.

PMID- 11530399
TI  - [Capacity and resistance parameters of the athlete's cardiovascular system and
      their dynamics in regular training].
AB  - Viscosity and elasticity of the cardiovascular system are assessed by a new
      method based on evaluation of correlations between deposit properties of the left
      ventricular chamber, aortic wall and vascular resistance in different parts of
      the arterial tree. This method examines individual hemodynamic characteristics of
      healthy untrained persons and hemodynamic changes due to regular training.

PMID- 11530401
TI  - [Mechanisms of adaptation effect of normobaric hypoxic therapy].
AB  - It was discovered that brain adaptation to long-term hypoxia operates primarily
      through lowering frequency of dominating spontaneous activity. EEG parameters can
      help in assessment of acute hypoxia and predict effectiveness of hypoxic therapy.
      Patients with definite response to rhythmic photostimulation in the range of
      alpha-activity tolerate hypoxia well. High presentation of slow waves in the
      pattern of the initial EEG, especially of teta-rhythm predicts formation of
      adaptive effect in hypoxic therapy.

PMID- 11530400
TI  - [Evaluation of the effectiveness of normobaric hypoxia and low-intensity laser
      radiation in hypertensive patients from 24-hour arterial pressure monitoring
      data].
AB  - A randomized parallel study was performed to compare the antihypertensive effect
      of normobaric hypoxia and low energetic laser irradiation in 57 patients with
      essential hypertension stage I using 24-hour blood pressure monitoring. High
      hypotensive efficacy of both methods is demonstrated. A course of normobaric
      hypoxia decreased mean 24-h and mean daytime systolic and diastolic blood
      pressure. Low energetic laser irradiation reduced mean 24-h, mean daytime and
      mean night systolic and diastolic blood pressure.

PMID- 11530402
TI  - [Effect of acute normobaric hypoxia on electrical stability of the myocardium in
      healthy people].
AB  - We studied the impact of acute 10-min normobaric hypoxia on myocardial electrical
      stability, systolic and diastolic cardiac functions in 10 young healthy men.
      Hypoxia induced a decrease of ejection fraction and left ventricular early peak
      filling velocity. The QTc interval was prolonged during normobaric hypoxia
      without QT dispersion increase. Electrocardiographic investigation with
      assessment of QT-interval must be mandatory before normobaric hypoxic therapy is
      started. Prolonged QT interval is contraindication to normobaric hypoxic therapy.

PMID- 11530403
TI  - [Use of traditional methods in medicine for treating moderately severe bronchial
      asthma].
AB  - Minor therapeutic "cups" bloodletting, a variety of little known in Russia but
      conventional in China method, was compared in efficiency to chemotherapy,
      acupuncture and phytotherapy in allergic and non-allergic forms of bronchial
      asthma. The bloodletting alone or in combination with acupuncture and
      phytotherapy stabilizes the course of asthma and prevents asthmatic attacks,
      reduces routine doses of necessary broncholytics and glucocorticosteroids.

PMID- 11530404
TI  - [Efficacy of therapeutic use of ultrasound and sinusoidal modulated currents
      combed with halotherapy in patient with occupational toxic-dust bronchitis].
AB  - Immunological and cardiorespiratory characteristics were studied in 88 alloy
      industry workers with occupational toxic-dust bronchitis who received the
      following therapy: sinusoidal modulated currents (SMC), ultrasound (US) on the
      chest, halotherapy (HT) (52 patients, group 1); SMC + HT (10 patients, group 2);
      US + HT (15 patients, group 3); HT (11 patients, group 4). The patients did also
      therapeutic exercise and were massaged (chest). It was found that device
      physiotherapy (SMC, US) in combination with HT raise the treatment efficacy to
      86.5%. This combined treatment is recommended both for treatment and prevention
      of obstructive syndrome in toxic-dust bronchitis.

PMID- 11530405
TI  - [Combined effect of insolation and drinking mineral waters on hormonal and immune
      status in medium-height mountains.(Experimental study)].
AB  - 80 Wistar male rats were kept for 24 days in moderate altitude conditions of
      mountain resort Teberda. Before the experiment and after it their blood was
      examined with enzyme immunoassay for hydrocortisone, T3, T4, TSH, with
      radioimmunoassay for insulin; glucose levels, dynamics of peripheral blood count,
      immune status were also measured. It was found that UV radiation has a negative
      effect on hormonal and immune status of healthy rats in medium-high mountains
      (hydrocortisone levels fell by 50%, insulin rose 5-6-fold, CIC rose by 24.2%,
      eosinophils count rose 3-fold, T-cell immunity and lymphocyte phagocyting
      activity got suppressed, lymphocyte/neutrophil proportion reduced by 35%. Intake
      of mineral water corrected all the negative effects of insolation but
      hyperinsulinemia decreased insignificantly.

PMID- 11530406
TI  - [Effectiveness of manual therapy in rehabilitating patients with ischemic heart
      disease].
AB  - Physiotherapy with neuromuscular manual techniques was applied in programs of
      rehabilitation of IHD patients with reflex pain syndromes or associated
      osteochondrosis or early after surgery. Elimination of reflex pain syndromes in
      the above patients raises the treatment efficacy, improves functional state of
      the cardiorespiratory system.

PMID- 11530407
TI  - [Status of the immune system in irritable bowel syndrome patients and effect on
      interference currents].

PMID- 11530409
TI  - [Use of automated information systems by sanatoria].

PMID- 11530410
TI  - [Qualitative assessment of recreational possibilities for climatic resorts].

PMID- 11530408
TI  - [Lipid profile dynamics in patients with chronic acalculus cholecystitis treated
      with sulfide mud].

PMID- 11530411
TI  - [Combined use of therapeutic exercise and acupuncture in treating patients with
      post-traumatic contractures on upper extremity joints].

PMID- 11530412
TI  - [Experience in treating children with vegetative dystonia syndrome].

PMID- 11530413
TI  - [General geomagnetic therapy and its role in combined treatment of duodenal ulcer
      disease].

PMID- 11530414
TI  - [The problem of training medical personnel for sanitoria].

PMID- 11530415
TI  - [Problems of introducing scientific-methodical innovations in sanitorium
      treatment and physiotherapy into health care].

PMID- 11530416
TI  - [Therapeutic factors from the Dead Sea].

PMID- 11530417
TI  - [Ozone baths in santorium-spa treatment of patients with ischemic heart disease].

PMID- 11530418
TI  - [Ultrasound in treating cardiac dysrhythmia].
AB  - Ultrasound was used in the treatment of cardiac arrhythmia. Suppression of
      automatic activity of pacemaker cells, a trend to reduction of AV junction
      transmittancy and prolongation of its refractory period in response to specially
      programmed ultrasound may contribute to elimination of tachyarrhythmia paroxysms
      in some patients. Ultrasound therapy should be used with caution in suspicion of
      sinus insufficiency and AV junction failure. Ultrasound in the treatment of
      cardiac arrhythmia seems perspective and requires further studies.

PMID- 11530419
TI  - Phenomenology of tics and natural history of tic disorders.

PMID- 11530420
TI  - Neuropsychological function in Tourette syndrome.
AB  - The accumulated body of scientific evidence regarding intellectual function,
      presence of learning disorders, and specific neuropsychological deficits in TS
      suggests that difficulties in these areas are present in a significant percentage
      of patients with TS. Despite the numerous methodological shortcomings of past
      neuropsychological studies of TS, relatively robust and consistent findings have
      emerged. The literature to date has suggested that intellectual ability is
      normally distributed in TS. Whether or not individuals with TS have significant
      discrepancies between their verbal and nonverbal abilities remains unclear. The
      prevalence of learning disabilities in TS has been reported to be similar to the
      base rates reported for the general population, although there is evidence to
      suggest that the prevalence of LDs in children with TS may actually be lower and
      specific for difficulties in math and written language. Specific cognitive
      deficits in TS consist of visuomotor integration problems, impaired fine motor
      skill, and executive dysfunction. The presence of comorbid conditions, notably
      ADHD and OCD, appears to significantly increase the likelihood that an individual
      with TS will also have learning problems or some demonstrable cognitive
      impairment. The presence of a learning disability, specific academic deficiency,
      or cognitive deficit may pose a greater obstacle for persons with TS than the tic
      disorder itself. This is particularly salient for children with TS, who may be at
      a higher risk for poor school performance and academic failure. The psychosocial
      impact of these problems is also far-reaching. Given the recent emphasis on the
      early detection of academic and learning problems, it would seem prudent that
      children with TS who are suspected of having neuropsychological difficulties be
      evaluated as soon as possible. There are numerous educational interventions and
      accommodations available to children with LDs and/or specific academic weaknesses
      that can work equally well in children with TS. The available body of scientific
      evidence suggests that persons with TS have normally distributed intellectual
      ability. This would suggest a diminished role for routine IQ testing unless there
      is compelling clinical evidence to suggest that the IQ score be obtained, such as
      when the individual is suspected of having an LD. Given that children with TS may
      be particularly at risk for learning disabilities or academic deficiencies in
      math and written language, a complete psychoeducational workup should be
      conducted on any child with TS who is suspected of having such difficulties. This
      evaluation should be conducted as early as possible, so that educational
      interventions can be implemented. Traditionally, the psychoeducational evaluation
      is performed by the school psychologist and should include standardized IQ
      assessment and academic achievement testing that can objectively identify and
      quantify the nature and severity of the learning problem. Once the problem has
      been documented, the school psychologist should recommend appropriate educational
      and remedial interventions. In addition to psychoeducational testing,
      neuropsychological testing is indicated to identify specific cognitive deficits
      that might be present in children with TS, notably problems with visuomotor
      integration, motor skill, and executive function. The psychoeducational
      evaluation performed by the school psychologist typically does not assess these
      cognitive functions. Therefore, referral for neuropsychological testing is
      indicated if there is a strong clinical suspicion of cognitive deficits. The
      accumulated neuropsychological literature in TS suggests that a broad-based,
      comprehensive, and lengthy neuropsychological examination is not necessary,
      however. At a minimum, the neuropsychological test battery should include
      assessment of visuomotor integration ability, motor skills, spatial/perceptual
      abilities, and executive function. This type of assessment would take less time
      to complete and has greater sensitivity and specificity for identifying
      neurocognitive deficits that are believed to be unique to TS. Neuropsychological
      functioning continues to be an important component in understanding the full
      neurobehavioral spectrum of TS. At present, there is great opportunity to explore
      neuropsychological functioning in TS with newly emerging technology such as
      functional magnetic resonance imaging (fMRI), positron emission tomography (PET),
      and related techniques that assess cortical metabolic activity, as well as newer
      electrophysiological techniques. This technology, notably fMRI, allows
      investigation of neuropsychological functioning in vivo and may reveal important
      clues to the neuroanatomic substrates of neuropsychological impairment of
      learning disabilities in TS.

PMID- 11530421
TI  - Neurobiology of basal ganglia circuits in Tourette syndrome: faulty inhibition of
      unwanted motor patterns?

PMID- 11530422
TI  - The neurobiology of repetitive behaviors: clues to the neurobiology of Tourette
      syndrome.

PMID- 11530423
TI  - Cognitive function paradigms: implications of neurophysiological studies of
      dopamine stimulants for Tourette syndrome and comorbid attention-deficit
      hyperactivity disorder.

PMID- 11530424
TI  - Differential diagnosis and etiology of tics.

PMID- 11530425
TI  - Neuropathology in Tourette syndrome: an update.

PMID- 11530426
TI  - Neurochemistry and synaptic neurotransmission in Tourette syndrome.

PMID- 11530427
TI  - Neuroimaging studies of Tourette syndrome: a decade of progress.

PMID- 11530428
TI  - Neural substrates of attention-deficit hyperactivity disorder.

PMID- 11530430
TI  - Transcranial magnetic stimulation (TMS) as a research tool in Tourette syndrome
      and related disorders.
AB  - TMS is a technology with much promise for understanding brain function in health
      and disease. This chapter has reviewed the physics and safety of this new tool.
      Much basic work remains to be done in order to understand exactly how TMS affects
      neurons, and the roles that intensity, frequency, and location have on brain
      activity. Recent work combining TMS with imaging is showing the method for future
      advances. In the area of TS, TMS has already had a significant impact; 3 studies
      have hinted that TS patients have a deficient inhibitory system. Other
      investigators are exploring whether TMS might be used in a therapeutic manner to
      alter the behavior of dysfunctional circuits. These areas of applying TMS to
      understanding and perhaps treating TS show much promise. Nonetheless, a great
      deal of basic work is likely needed before TMS can be fully used as a research
      tool or treatment modality for TS.

PMID- 11530429
TI  - Probing striato-thalamic function in obsessive-compulsive disorder and Tourette
      syndrome using neuroimaging methods.
AB  - In summary, contemporary pathophysiological models of OCD and related disorders
      implicate CSTC circuitry. In this chapter, we have reviewed relevant concepts
      related to implicit learning and more specifically, the use of an implicit
      sequence learning paradigm as a probe of striato-thalamic function. An initial
      PET investigation of patients with OCD confirmed a priori hypotheses of failure
      to recruit right striatum, despite the absence of a performance deficit (22). A
      modified version of the SRT was studied in conjunction with fMRI and yielded
      reliable right-lateralized striatal activation in a cohort of 10 male subjects,
      with clear spatial dissociation of caudate and putamen activation foci (119).
      Subsequent studies in our laboratory suggest that this paradigm also yields a
      reliable temporal window of thalamic deactivation, and hence a means for
      assessing thalamic gating in human subjects (120). Finally, as presented in this
      chapter, preliminary data from the fMRI-SRT in patients with OCD and TS as well
      as normal control subjects appear to replicate and extend the findings from our
      original PET-SRT study in OCD. Future investigations in our laboratory will seek
      to elaborate upon these preliminary results. In particular, we intend to study
      psychiatric comparison groups to establish the generalizability and/or
      specificity of these findings across disorders. Within OCD, we hope to explore
      the relationship between abnormal brain-activation patterns and symptom
      dimensions (34). Further, by studying subjects with remitted OCD who have been
      successfully treated, we hope to determine whether the observed brain-activation
      abnormalities represent state or trait markers. Finally, we have already begun to
      test a hypothesis of parallel processing deficiency in OCD by using a dual-task
      version of the SRT that makes simultaneous demands on implicit and explicit
      information processing systems (128). It is our hope that this program of
      research will yield new insights about OCD and related disorders, including TS.
      Most importantly, as other teams of investigators pursue complementary lines of
      inquiry, it is our wish that collective efforts in this field will lead to
      improved diagnosis and treatment, if not cure or prevention, for those who are
      afflicted with these illnesses.

PMID- 11530431
TI  - Neurophysiology of tics.

PMID- 11530432
TI  - Sleep and Tourette syndrome.

PMID- 11530433
TI  - The epidemiology of tics and Tourette syndrome in children and adolescents.

PMID- 11530434
TI  - Epigenetic and environmental risk factors in Tourette syndrome.

PMID- 11530435
TI  - Update on the genetics of Tourette syndrome.
AB  - There has been significant progress in the understanding of the genetics of TS
      since the last international symposium. At the present time, we stand at the
      threshold of identifying the regions harboring the genes important in the
      manifestation of this syndrome. The localization and characterization of genes
      important for the expression of the TS phenotype will be a major advance in our
      understanding of the pathogenesis of this disorder and will also provide a model
      for the study of other developmental disorders. Unquestionably, the replication
      of these initial linkage findings and the localization and characterization of
      genes responsible for the expression of TS and related disorders will be a major
      step forward in our understanding of the genetic/biologic risk factors important
      for the expression of these disorders. Furthermore, once genes conferring
      susceptibility to TS and associated behaviors have been characterized, further
      work will allow the identification of additional nongenetic factors that are
      important for the manifestation or the amelioration of the symptoms of the
      disorders (84). As discussed by Kidd (85) and Pauls (84), the identification of a
      linked marker will permit the design of much more incisive studies to illuminate
      the physiological/biochemical etiology of TS by examination of the gene product
      and its impact on the development of the disorders. On the other hand, by
      controlling for genetic factors, through the genetic case-control research
      paradigm (85), it will be possible to document more carefully the
      environmental/nongenetic factors important for the expression of TS and other
      disorders.

PMID- 11530437
TI  - Could Tourette syndrome be a neurologic manifestation of rheumatic fever?

PMID- 11530436
TI  - Group A streptococcal infections and their potential role in neuropsychiatric
      disease.

PMID- 11530438
TI  - Rating scales and quantitative assessment of tics.

PMID- 11530439
TI  - Therapeutic implications of immunology for tics and obsessive-compulsive
      disorder.

PMID- 11530440
TI  - Behavioral treatments for Tourette syndrome and tic disorders: state of the art.

PMID- 11530441
TI  - Modulation of prefrontal cortical-striatal circuits: relevance to therapeutic
      treatments for Tourette syndrome and attention-deficit hyperactivity disorder.

PMID- 11530442
TI  - Clinical psychopharmacology for Tourette syndrome and associated disorders.

PMID- 11530443
TI  - Update on the treatment of tics.

PMID- 11530444
TI  - Insight and hindsight into Tourette syndrome.

PMID- 11530445
TI  - Tourette syndrome: pieces of the puzzle.

PMID- 11530446
TI  - The tic-related obsessive-compulsive disorder phenotype and treatment
      implications.

PMID- 11530447
TI  - Tourette disorder and ADHD.

PMID- 11530448
TI  - Emotional and behavioral difficulties associated with Tourette syndrome.

PMID- 11530449
TI  - Autism spectrum disorders: relevance to Tourette syndrome.

PMID- 11530450
TI  - [Headache syndrome in children with autonomic dysfunction].
AB  - Morbidity analysis of 350 children from somatic hospital has revealed clinical
      manifestations of autonomic dystonia syndrome (ADS) in 36% of the cases in the
      form of gastrointestinal, cardiovascular disorders, headache syndrome, etc. It
      was found that in the patients with a prevalence of vagotonia clinical
      manifestations of ADS rose at earlier age and differed by more variety than in
      combined and sympathotonic types of autonomic homeostasis. Headache syndrome was
      rather frequent in ADS and was observed in 35% of the patients. In children with
      vagotonic type of ADS, a headache syndrome presented most frequently (43%) in the
      forms of migraine and headache of tension (HAT). Clinical manifestations of
      autonomic dystonia were more pronounced in children with HAT. Meanwhile,
      autonomic dysfunction had hereditary origin and was milder in periods between the
      attacks in cases of migraine.

PMID- 11530451
TI  - [Clinical manifestations of migraine in children].
AB  - 100 case records of children aged 2.5 to 15 years with main complaints of
      headache (HA) examined and treated in Children's Neurologic Department were
      analyzed. For making the diagnosis more precise, diagnostic criteria of
      International Society for HA Investigation (1988) were used. Migraine was
      diagnosed in 25 children (10 boys, 15 girls), the age of its debute was from 2.5
      to 13 years. Migraine with aura was found in 36% of the children. Clinical
      picture of the attack was characterized by polymorphism, the HA attacks were more
      severe, but shorter, than in adults. HA attacks were arrested quite frequently by
      sleep or rest without any drugs. Hereditary analysis revealed migraine in 36% of
      the parents. CNS damage was found in the anamneses of 64% of the patients, a
      closed craniocerebral trauma in 40% of the cases. Clinical and neurophysiologic
      study didn't reveal any specific disturbances, though pronounced psychoautonomic
      disorders were quite frequent in children with migraine.

PMID- 11530452
TI  - [Psycholinguistic studies of the dreams of children and adolescents with neurotic
      disorders].
AB  - 78 patients with neurotic disorders, 46 patients with cerebral organic pathology
      (tumors of the brain, epilepsy) and 25 healthy individuals were examined. Their
      age was 10-17 years. Clinical, paraclinical, experimental-psychologic,
      psycholinguistic methods were used. Psycholinguistic analysis of the reports
      concerning the dreams of the children and juveniles was performed by means of
      original computer system of the analysis of the meaning of the texts and by
      specially elaborated scheme for categorization of the words. Neurotic patients
      had a significant quantitative and qualitative peruliarity of speech which
      reflected stable changes in patients' personality concerning the sphere of
      meaning.

PMID- 11530453
TI  - [Clinical and neurochemical features of depressive syndrome in neuroses and
      slowly progressive schizophrenia].
AB  - The examination was made of 78 patients (57 women, 21 men) with depression of
      neurotic level in slow progredient neurosis-like schizophrenia or neurosis. In
      all the cases of neuroses depressive syndrome correlated with relevant premorbid
      structure of the person. Meanwhile, such correlation was not clearly observed in
      schizophrenic patients. Complication of the clinical picture of the depression
      wasn't the same in cases of schizophrenia and neuroses, and resulted from
      productive symptomatics of different registers. The results of neurochemical
      studies evidence, that physiologic inactivation of serotonin, in terms of a
      removal of the active molecules from a zone of interaction with the receptors,
      was considerably increased in patients with neuroses as compared with
      schizophrenic patients. This suggests treatment of neurotic patients with the
      drugs, which inhibit serotonin reuptake selectively.

PMID- 11530454
TI  - [Age-related factors of psychopathology of impulse control disorders].
AB  - 15 children and adolescents with impulse control disorders (mean age 12.9 years)
      were examined. These disorders were presented as dromomania, kleptomania,
      aggressive-sadistic actions, tricholillomania, pyromania; a combination of
      different types was observed in some cases. Schizophrenia was diagnosed in 7
      cases, affective disorders--in 8 patients. Independently of the nosologic unity
      of the disease, development of the impulse control disorders took place in
      affective disorders which manifested either by monopolar course (depression) (11
      cases), or by bypolar attacks with unclear outlines of the phases (4 patients).
      Psychopathology of impulse control disorders in children and juveniles was
      analogous to that of the adults, however, their structure wasn't so complex and
      development of the phases wasn't so clear.

PMID- 11530455
TI  - [Use of citrulline malate (stimol) in patients with autonomic dystonia associated
      with arterial hypotension].
AB  - To study possibilities of a therapeutic correction of asthenic syndrome in
      individuals with chronic arterial hypotension with malate citrulline, the study
      was made of 12 women and 3 men with psychoautonomic syndrome (autonomic
      dystonia), combined with chronic constitutional arterial hypotension. Their age
      was from 27 to 45 years (mean age--37.6). A control group comprised 14 healthy
      individuals. Both a state of autonomic nervous system and manifestations of
      arterial hyportension were analyzed by means of complex scored questionnaires.
      Mental condition was assessed by the tests of Spilberger (evaluation of reactive
      and personal anxiety) and of Beck (estimation of depressive manifestations). In
      all the examined individuals with chronic arterial hypotension, there was
      psychoautonomic syndrome combined with complaints to asthenic manifestations,
      namely, to low performance and fatigue. Stimol was prescribed in the form of 50%
      solution in daily dose of 6 g (3 administrations). The therapy resulted in
      regression of clinical manifestations of both psychoautonomic syndrome and
      asthenic symptoms. A mechanism of the drug's action works through favourable
      changes in cerebral and muscular cells, that, in turn, had an influence on other
      manifestations of psychoautonomic syndrome.

PMID- 11530456
TI  - [Prozac treatment of chronic tension headache].
AB  - The paper summarizes the experience of therapy of chronic tension type headache
      (TTH) with prozac (fluoxetine)--a selective serotonine reuptake inhibitor. The
      data are presented concerning clinical psychologic examination of 20 outpatients
      with chronic TTH both before and after therapy with prozac in daily dose of 20 mg
      during 6 weeks. Background study of the patients revealed severe depression
      (according to Beck's and SCL-90 scales), anxiety (Spilberger scale) and
      alexitimia (Toronto scale). Before the treatment, a frequency of TTH attacks was
      at least four times a week, the intensivity was equal to 8.9 scores according to
      visual analogous scale. Together with a headache there were psychopathologic and
      psychoautonomic manifestations. After the course of therapy the headaches
      disappeared completely in 25%, while considerable improvement was observed in 75%
      of the patients. The levels of depression, anxiety, somatization have decreased
      significantly too. Side effects as well as withdrawal syndrome weren't found. The
      role of depression in formation of chronic TTH, as well as the role of alixetimia
      in formation of somatizated variation of the depression were considered.

PMID- 11530457
TI  - [Cerebrolysin and magnesium-B6 in the treatment of side effects of psychotropic
      drugs].
AB  - 51 patients were observed. Schizophrenia was diagnosed in 31 patients and
      endogenous depression in 20 cases. All the patients had extrapyramidal and somato
      vegetative side effects of neuroleptics and antidepressive drugs, and were
      resistant to conventional corrective therapy for at least a period of 3 weeks. In
      addition to current treatment of both basic disease and adverse effects,
      cerebrolysin was administered (5-10 ml i.v./dr, during 28 days) and magme B6 (20
      30 ml per os during 21 days). By the treatment end-point either moderate or
      marked reduction of extrapyramidal disorders (according to ESRS) was observed in
      74.4% of patients treated by cerebrolysin and in 72.2% treated by magne B6;
      somato-vegetative adverse effects reduced (by SARS) in 85.8% and in 83.8%
      respectively. Both drugs showed equally high efficacy against hyperkinetic and
      cardiovascular side effects (symptoms relief was in 59-62% and 65-69%,
      respectively). Cerebrolysin is more preferable in cases of side vegetative
      events, dysomnia and dysuria; magne B6 was more effective in correction of
      akineto-hypertonic and hyperkinetic-hypertonic syndromes as well as in
      cholinolytic side effects.

PMID- 11530458
TI  - [Neurology of the 21st century].

PMID- 11530459
TI  - [Peripheral mechanisms of the pathogenesis of cervical dystonia].
AB  - Peripheral mechanisms of pathogenesis and formation of the symptoms of cervical
      dystonia (spastic torticollis--ST) were investigated. By means of orthopedic
      diagnosis and analysis of motor stereotype, traumas, algesic syndrome in 40
      patients with ST, it was found a "short leg" on the side, opposite to the
      rotation of the head, frequent postural loads on the head and on the neck before
      ST rise, and algesic and other sensory symptoms in the same region. The data of
      neuromyography and of evoked skin sympathetic potentials show a presence of
      pathologic changes in sympathetic autonomic fibers as well as in axons of
      accessory nerve at both sides, mainly at the left. Such alterations were mainly
      peripheral and were found more frequently in a group of left-sided ST. The
      correlations observed between a side of the rotation of a head and a side of
      peripheral factor, permitted to suppose that peripheral factors (the factor of a
      "short leg" mainly) determined frequently a side of the rotation of the head. So,
      ST therapy must influence the peripheral mechanisms, but not only the central
      ones.

PMID- 11530460
TI  - [Motor potential and interhemispheric relations in patients with stroke].

PMID- 11530461
TI  - [Correlation between the level of autoantibodies to nerve growth factor and
      clinical features of schizophrenia in children].

PMID- 11530462
TI  - [Prevalence and nosology of mental disorders in the families of women with heart
      defects (a longitudinal study)].

PMID- 11530463
TI  - [Weakness of the sternocleidomastoid muscle: a diagnostic test in hysterical
      paralysis].

PMID- 11530464
TI  - [Possibility of the use of frozen human lymphocytes in the area of biological
      psychiatry].

PMID- 11530465
TI  - [A method of evoked potentials in the study of cognitive processes in
      schizophrenia].

PMID- 11530466
TI  - [The 8th World Congress, "Pain Clinic" (May 6-10, 1998, Canary Islands, Spain)].

PMID- 11530467
TI  - [Affective disorders and syndrome formation].
AB  - Investigation of affective disorders in different psychopathologic syndromes
      allows to evaluate their role in the processes of syndrome formation and
      prognostic value. Affective disorders developing in different diseases
      (nosologies) within relevant psychopathologic syndromes determine main
      peculiarities of the disease course as well as severity of damage to mental
      activity.

PMID- 11530468
TI  - Births, marriages, divorces, and deaths: provisional data for January-December
      2000.

PMID- 11530469
TI  - [Cerebral hemodynamics in patients with neurosensory hearing loss before and
      after magnetotherapy].
AB  - Magnetotherapy effects on cerebral hemodynamics were studied using
      rheoencephalography (REG). When the treatment results and changes in cerebral
      hemodynamics were compared it was evident that normalization or improvement of
      vascular status in vertebrobasilar and carotid territories registered at REG
      results in better hearing. This confirms the role of vascular factor in
      pathogenesis of neurosensory hypoacusis of different etiology and effectiveness
      of magnetotherapy in such patients.

PMID- 11530470
TI  - [Current problems of cochlear implantation].
AB  - The Center of Cochlear Implantation at St-Petersburg ENT Research Institute was
      set up in 1997. For three years of its activity 19 cochlear implantations were
      made in patients of different age. All of them received Combi 40/40+ implants
      (Med-El, Austria). Prospects of cochlear implantation and problems of its
      introduction in Russia are analysed.

PMID- 11530471
TI  - [Reconstruction of the chain of the auditory ossicles after radical operation on
      the middle ear].
AB  - As restoration of hearing in patients after radical surgery on the middle ear for
      otitis media purulenta chronica remains topical, we tried to increase the
      efficacy of ossiculoplasty in such patients by staged reconstruction of the
      middle ear. A total of 102 patients were examined and operated on. A modified
      classification of osseous chain defects was used to evaluate the degree of damage
      to the osseous system. The following policy was employed for reconstruction of
      the middle ear: in patients with large trepanation cavities (more than 5 ml)
      mastoidoplasty was carried out as the first stage using a musculo-periosteal flap
      with an anterior or inferior pedicle; at the second stage, myringoplasty was
      performed using a two-layer graft followed by ossiculoplasty with autotransplants
      (fingernail plate, auricular or tragal cartilage, cortical layer bone). Long-term
      follow-up of the patients showed that good and satisfactory hearing levels were
      obtained in 79.4% of the patients. The air-bone gap was closed by 10 dB or more
      in the speech frequency range in 80.4% of the patients. Staged reconstruction of
      the middle ear using autotransplant materials significantly decreased the number
      of postoperative complications (perforation of the plastic flap, cicatrical
      displacement of the prosthesis and graft rejection).

PMID- 11530472
TI  - [Impedance audiometric characteristics of hearing after hearing improving
      operations].
AB  - A complete audiological examination including impedance audiometry conducted in
      patients with otitis media purulenta chronica (n = 22), adhesive otitis media (n
      = 20), otosclerosis (n = 14) and family hypoacusis (n = 8) has detected signs of
      neurosensory hypoacusis (NH). Follow-up results indicated NH progression. Thus,
      affection of the middle ear manifests with symptoms of conductive and
      neurosensory hypoacusis. NH was treated surgically with temporary effect.

PMID- 11530473
TI  - [Clinical classification of benign ENT tumor].
AB  - The proposed clinical classification of benign ENT tumors is based on division of
      anatomic regions (the ear, nose, pharynx, larynx) into sections and fragments and
      allows to assess the spread of any ENT tumor. Moreover, it agrees with TNM
      classification. The symbols "T" and R are used which denote four variants (T1-4)
      or R1-4 for the tumor and recurrence, respectively.

PMID- 11530474
TI  - [Approaches to classification of laryngeal resections].

PMID- 11530475
TI  - [Microflora in ENT and CNS diseases in patients living in the Moscow region].
AB  - Patients with ENT and CNS inflammation living in the Moscow Region have been
      examined for pathogenic contamination of relevant clinical samples. The
      microflora changes were followed up, pathogenic agents of high and moderate
      priority were identified. It is shown that for Moscow Region, ENT and CNS
      purulent inflammation is associated primarily with coagulase-negative
      staphylococci, E. coli, meningococci, S. viridans and yeast fungi.

PMID- 11530476
TI  - [Outpatient surgery in otorhinolaryngology].
AB  - 86 ENT operations have been performed in the day outpatient hospital. Basing on
      this experience, the authors present criteria of the patients' selection for the
      outpatient surgery, describe preoperative preparation of the patients and
      criteria of safe discharge from the hospital. The list of the operations which
      can be performed in a day hospital is given as well as results of the operations
      in it. Postoperative complications were not registered. The treatment results
      enable the authors to advocate wider spectrum of ENT operations for carrying out
      in ambulatory setting (in a day hospital).

PMID- 11530477
TI  - [Immunological status of patients with juvenile angiofibroma of the skull base].
AB  - Immunological status was studied in 20 patients with juvenile angiofibroma of the
      base of the skull (JABS). An imbalance in the immune system was found, especially
      in cellular immunity (low number of T-helper and high level of T-suppressor
      lymphocytes, subnormal index of their proportion). The number of activated T
      cells decreased, while that of NK-cells increased. JABS patients have an elevated
      level of serum IgA.

PMID- 11530478
TI  - [Photon hemotherapy:correction of metabolic hepatic disorders in neurosensory
      hypoacusis].
AB  - Hepatic metabolism, blood rheology and lipid peroxidation were studied in 160
      patients with neurosensory hypoacusis (63 of them had acute and 97 chronic
      hypoacusis) aged 35 to 74 years before and after photon hemotherapy. Abnormal
      values of the above parameters and changes in lipid metabolism were related.
      Photon hemotherapy was an effective corrector of hepatic metabolism disorders.

PMID- 11530479
TI  - [Ultracaine anesthesia in submucous resection of the nasal septum].
AB  - Ultracaine anesthesia in submucous resection of the nasal septum was performed in
      18 patients 17 to 42 years of age. Ultracaine anesthesia in submucous resection
      of the nasal septum is characterized by a good analgetic effect; absence of
      toxic, vegetative and other side effects; a good anematizing effect; a quick
      action of the anesthetic; long-term anesthesia in the operative field; reduced
      duration of the operation; small quantity of the anesthetic providing total
      anesthesia. Ultracaine is recommended as an optimal anesthetic in local
      anesthesia in submucous resection of the nasal septum.

PMID- 11530480
TI  - [Effects of the size and position of the anastomoses on pathological process in
      the paranasal sinuses].
AB  - In small anastomoses of the paranasal sinuses blocking in inflammation we observe
      acute pyo-exudative inflammation; in large anastomoses--chronic productive form
      with development of the cysts and polyps. By the authors' experience, 8-10% of
      the population have no maxillary anastomosis in the crescentic fissure. It
      locates in the posterior part of its medial wall.

PMID- 11530481
TI  - [Orbital and intracranial complications of rhinosinusitis].
AB  - Rhinogenic orbital and intracranial complications occur in 0.8 and 0.01% of
      patients with rhinosinusitis, respectively. The author recognizes 9 and 8 forms
      of rhinogenic orbital and intracranial complications, respectively. Conservative
      treatment is preferable in non-purulent orbital and intracranial complications
      resultant from acute inflammation of the paranasal sinuses. In the above
      complications taking place in chronic paranasal inflammation it is valid to
      conduct a sanitizing operation on the paranasal sinuses. Purulent intracranial
      and orbital complications dictate the necessity of major surgical treatment of
      the affected paranasal sinuses and intracranial focus in active antibacterial,
      dehydration, desensitizing and strengthening therapy. Prognosis of the orbital
      and intracranial complications at present is more favourable.

PMID- 11530482
TI  - [Otological microscopic examination of patients with middle ear pathology].

PMID- 11530483
TI  - [Topical corticosteroids in the treatment of allergic rhinosinusitis].

PMID- 11530484
TI  - [Bioparox in the treatment of sinusitis].

PMID- 11530485
TI  - [Treatment of concussion and contusion of ear].

PMID- 11530486
TI  - [A case of extrapulmonary tuberculosis with laryngeal and intestinal
      involvement].

PMID- 11530487
TI  - [Psychogenic aphonia in a female with nodular goiter].

PMID- 11530488
TI  - [Long term stay of a foreign body in the lower respiratory tract in chronic
      pneumonia].

PMID- 11530489
TI  - [A large foreign body in the esophagus].

PMID- 11530490
TI  - [A case of a delayed intracranial complication in a man with severe
      craniocerebral injury].

PMID- 11530491
TI  - [Paratonsillar abscess in a 2-month old child].

PMID- 11530492
TI  - [Laryngeal tuberculosis].

PMID- 11530493
TI  - [Pharmacological therapy of severe purulent-inflammatory ENT diseases and their
      complications].

PMID- 11530494
TI  - [Production of hematopoietic cells from ES cells].
AB  - Murine embryonic stem (ES) cells are cell lines established from blastocyst which
      can contribute to all adult tissues, including the germ-cell lineage, after
      reincorporation into the normal embryo. ES cell pluripotentiality is preserved in
      culture in the presence of LIF. LIF withdrawal induces ES cell differentiation to
      nervous, myocardial, endothelial and hematopoietic tissues. The model of murine
      ES cell hematopoietic differentiation is of major interest because ES cells are
      non transformed cell lines and the consequences of genomic manipulations of these
      cells are directly measurable on a hierarchy of synchronized in vitro ES cell
      derived hematopoietic cell populations. These include the putative hemangioblast
      (which represents the emergence of both hematopoietic and endothelial tissues
      during development), myeloid progenitors and mature stages of myeloid lineages.
      Human ES cell lines have been recently derived from human blastocyst in the USA.
      Their manipulation in vitro should be authorized in France in a near future with
      the possibility of developing a model of human hematopoietic differentiation.
      This allows to envisage in the future the use of ES cells as a source of human
      hematopoietic cells.

PMID- 11530495
TI  - [Anti-tumor immunotherapy based on dendritic cells].
AB  - In cancer immunotherapy, the use of dendritic cells (DC) loaded with tumor
      associated antigens (TAA) emerged as a promising strategy. We initiated 3 pilot
      clinical trials with immunological endpoints using TAA loaded autologous DC.
      These trials showed that this approach was safe and associated with the induction
      of potent TAA specific IFN-gamma responses, which were transient despite the
      providing a further help through KLH presentation. Subcutaneous (s.c.) IL-2
      administration was associated with long-lasting TAA specific IL-5 production.
      Clinical responses were observed in about 1/3 of the patients. Further
      improvements will take advantage of the use of a new type of DC cells (IL-3/IFN
      beta DC) and of tumor cell-DC hybrids.

PMID- 11530496
TI  - [Exosomes derived from dendritic cells].
AB  - Dendritic cells (DC) are potent antigen presenting cells and the only ones
      capable of inducing primary cytotoxic immune responses both in vivo and vitro.
      DCs secrete a 60-80 nm membrane vesicle population of endocytic origin, called
      exosomes. The protein composition of exosomes was analyzed using a systematic
      proteomic approach. Besides MHC and costimulatory molecules, exosomes bear
      several adhesion proteins, probably involved in their specific targeting.
      Exosomes also accumulate several cytosolic factors, most likely involved in
      exoxome's biogenesis in late endosomes. Like DCs, exosomes induce potent anti
      tumor immune responses in vivo. Indeed, a single injection of DC-derived exosomes
      sensitized with tumor peptides induced the eradication of established mouse
      tumors. Tumor-specific cytotoxic T lymphocytes were found in the spleen of
      exosome treated mice, and depletion of CD8+ T cells in vivo inhibited the anti
      tumor effect of exosomes. These results strongly support the implementation of
      human DC-derived exosomes for cancer immunotherapy.

PMID- 11530497
TI  - [Transplantation of normal or genetically modified myoblasts for the treatment of
      hereditary or acquired diseases].
AB  - The clinical trials of myoblast transplantation in Duchenne Muscular Dystrophy
      (DMD) patients produced disappointing results. The main problems responsible for
      these poor results have since then been identified and partially resolved. One of
      them was related to the use of an inadequate immunosuppression and, since then,
      immunosuppression with FK506 has permitted successful myoblast transplantation
      not only in mice but also in monkeys. The requirement for a sustained
      immunosuppression may be eventually avoided by developing a state of tolerance to
      the allogeneic cells or by autologous transplantation of genetically corrected
      myoblasts or stem cells. The rapid death of 75-80% of the injected myoblasts
      during the first five days has also contributed to the limited success of the
      early trials. This death was due to an inflammatory reaction and has been
      compensated in animal experiments by the injection of a larger number of cells
      (30 millions per cc). Finally, the myoblasts migrated only 0.5 mm away from their
      site of injection. This problem is currently compensated in animal experiments by
      injecting the myoblasts at every mm. The number of injections required may
      eventually be reduced by transfecting myoblasts with one or several
      metalloproteinase genes. The very good results obtained during the last two years
      in primates permit us to undertake a new phase I clinical trial to verify that
      myoblast transplantation can lead to the formation of muscle fibers expressing
      normal dystrophin in muscles of DMD patients.

PMID- 11530500
TI  - [Regenerative medicine].
AB  - Regenerative medicine can be defined as the possibility to replace aged/damaged
      cells by genetically similar young and functional cells. This could be reached by
      using human embryonic stem cells, eventually from cloned human embryos, or
      pluripotent adult stem cells. The range of the possible differentiation fates of
      these latter cells has recently been shown to be strikingly large. Although
      considerable works remains necessary to develop this new type of medicine, to
      assure its efficacy and safety, it nevertheless represents one of the major
      medical breakthroughs expected for the future.

PMID- 11530498
TI  - [Lineage-switching by pluripotent cells derived from adults].
AB  - When proceeding normally, embryonic morphogenesis begins with germ layer
      formation through the process of gastrulation. Each primordial germ layer gives
      rise to a particular set of lineages. Until recently, it was considered that fate
      switches between germ layers were impossible. In the last two or three years
      however, a fair number of such switches have been described (Table I), the most
      spectacular of which entails the differentiation of neural stem cells into
      various derivatives. This unexpected plasticity opens important prospects for
      cell therapy. Stem cells, which are the cells that display this plasticity, are
      defined by the two properties of self renewal and pluripotency. They are set
      apart during ontogeny and are responsible for maintaining the homeostasis of a
      tissue. This notion, first established in the case of hematopoietic stem cells
      was later extended to other fast renewing cells, such as those in the intestinal
      epithelium or epidermis, and more recently to cells reputedly non-renewable, i.e.
      neurons. A new strategy has been described, which has the interesting feature
      that it can be applied to the isolation of stem cells from various lineages. It
      consists in sorting out cells on the basis of the efflux of Hoechst 33342 dye
      (Goodell et al., 1996). When a cell suspension stained with this dye is examined
      under two distinct wave lengths, a "side population" (SP), characterized by weak
      fluorescence, can be identified and sorted out. The dye efflux property of these
      cells is due to the activity of the mdr (multidrug resistance) gene, which
      encodes a protein responsible for the building of a canal which serves to extrude
      toxins from the cells. A means of distinguishing a truly multipotent stem cell
      from a progenitor committed to a specific lineage has been reported. This
      consists in the expression of the Pax7 gene. Pax7-/- mouse muscles have no
      satellite cells, i.e. they miss the cells normally responsible for the
      regeneration of muscle. In contrast they do have an SP population. These SP cells
      are incapable of differentiating into muscle, but give rise to 10 times more
      hematopoietic colonies, when cloned in vitro, than SP cells from wild type muscle
      do. Thus Pax7 appears to be a commitment gene, in the absence of which stem cells
      cannot become specified to the muscle lineage. As a conclusion, this review
      emphasizes various features of the recent findings: 1) the unexpected plasticity
      uncovered in recent years is restricted to the stem cells of each tissue; 2) the
      switch in phenotype has to be "forced" on these stem cells by drastic
      experimental conditions enforced in the host: often sublethal irradiation is
      superimposed on a genetic deficiency. Progress in this field, concerning both
      conceptual and applied aspects, will require the identification of the factors
      characterizing the niches which promote integration and fate switches of stem
      cells, probably a combination of growth factors and intercellular interactions.
      Finally a key issue, before any therapeutical applications can be considered, is
      how to control the proliferation of transplanted stem cells in their new
      environment.

PMID- 11530499
TI  - [Transplantation of autologous skeletal myoblasts in ischemic cardiac
      insufficiency].
AB  - Despite medical therapeutic advances, congestive heart failure (CHF), which is
      the common ultimate consequence of many primary cardiovascular diseases, remains
      a major and growing public health problem. Although orthotopic heart
      transplantation is the gold standard, there is now growing evidence that one
      therapeutic option could be cellular cardiomyoplasty. Autologous adult skeletal
      myoblast transplantation seems to be the most clinically relevant, compared with
      other cell types, in that it avoids immunosuppression therapy, availability and
      ethical issues. Previous experimental studies have documented the efficacy of
      myoblast transplantation in improving function of infarcted myocardium. Although
      the mechanisms involved in this improvement are not elucidated, it has been
      demonstrated convincingly enough to consider ripping to clinical trials.

PMID- 11530501
TI  - [10 years of substitution therapy for neurodegenerative diseases using fetal
      neuron grafts: a positive outcome but with questions for the future].
AB  - Fetal neural allografts have already proven their therapeutic value in several
      hundreds of patients with Parkinson's disease, and have very recently provided
      promising results for patients with Huntington's disease in our center. Fetal
      neurons integrate readily into the neural parenchyma of the adult hosts,
      differentiate into mature neurons and substitute, anatomically and functionally
      for lost host neurons. Notable clinical improvements have been obtained using
      this procedure. Nevertheless, a major obstacle hampers the development of the
      technique, that provoked by the logistic difficulty in retrieving and preparing
      the tissue. Indeed, this requires, for each surgical session, the organization of
      a chain of expertise which cannot be taken up by an external provider (e.g. a
      biotech company). This is difficult to organize outside of specialized research
      centers. The future of the technique relies, therefore, upon the design of
      alternative sources of tissue. Two different ways are currently explored very
      actively, namely xenografting of neurons of porcine origin and human stem cells,
      in particular derived from ES cells. In both cases, but in different ways, the
      goal of both techniques is to allow the organisation of cell banking systems,
      relieving the constraints of obtaining the collaboration of specialized
      obstetricians and biologists. Obstacles foreseen for these two alternative ways
      of fetal neurons to be are identified and research laboratories are actively
      exploring ways to overcome them.

PMID- 11530502
TI  - [Allotransplantation in utero and immortalization of primate fetal hepatocytes].
AB  - We are developing cell therapy approaches on non-human primates as a preclinical
      model for the treatment of hepatic metabolic diseases. In foetuses, the tissues,
      including liver, are in expansion, which should facilitate hepatocytes
      engraftment, and the immune system becomes fully mature only after birth. We have
      set out conditions for isolation of fetal hepatocytes from macaca mulatta at the
      end of the 2nd trimester of gestation (90-100 days), their cryopreservation and
      retroviral transduction. Two different routes of administration of hepatocytes
      were evaluated: the umbilical vein which was deleterious for the foetuses, and
      the intraparenchymatous injection which was well tolerated by the animals.
      Administration of hepatocytes into the hepatic parenchyma resulted in
      microchimerism and allogenic cells were visualized 9 days after transplantation.
      Another approach has been to immortalize simian foetal hepatocytes using a
      retroviral vector expressing SV40 Large T flanked by lox sites. A cell line has
      been established for 2 years, which is not tumorigenic when injected
      subcutaneously into nude mice and display characteristics of bipotent
      hepatoblasts, precursors of hepatocytes and biliary cells. After orthotopic
      transplantation into nude mice via the portal vein, these cells expressed albumin
      until the sacrifice of the animals (17 days). The next steps will be to define
      conditions for transplantation of retrovirally transduced fetal primary and/or
      immortalized hepatocytes into young foetuses (60 days of gestation) and post
      natally.

PMID- 11530504
TI  - [The Langerhans cell: from in vitro production to use in cellular immunotherapy].
AB  - Dendritic cells constitute a family of antigen presenting cells defined by their
      morphology and their capacity to initiate primary immune response. Langerhans
      cells are paradigmatic dendritic cells, described in 1868 by a young medical
      student, Paul Langerhans in Berlin. Langerhans cells are present with epithelial
      cells in the epidermis, bronchi and mucosae. After antigenic challenge,
      Langerhans cells migrate into the T cell areas of proximal lymph nodes where they
      act as professional antigen-presenting cells. Langerhans cells originate in the
      bone marrow and CD34+ hematopoietic progenitors are present in cord blood or
      circulating blood. They are actively involved in skin lesions of allergic contact
      dermatitis or atopic dermatitis, in cancer immunosurveillance and are infected by
      HIV in AIDS. Since 1992, Langerhans cells may be generated in vitro from CD34+
      cord blood or circulating blood progenitors by culture with GM-CSF and TNF alpha,
      as well as from peripheral blood monocytes by culture with GM-CSF, IL4 and TGF
      beta 1. The possibility to obtain from the blood, the circulating progenitors of
      dendritic cells and the subsequent possibility to harvest a large number of these
      cells through in vitro culture using growth factors, have given rise to several
      very interesting therapeutic perspectives, especially in the field of anti-cancer
      immunotherapy. In dermatology advanced studies have concerned malignant
      melanomas. Anti-melanoma immunization trials were performed in patients, through
      dendritic cells charged with melanoma antigens. Side effects appear to be
      limited. Injections of antigenically charged dendritic cells were performed
      subcutaneously, intravenously or in the lymph nodes. Positive clinical responses
      were obtained with, in some cases, complete remission of the metastasis. These
      results open a particularly interesting perspective in the field of cancer
      treatment.

PMID- 11530503
TI  - [T-cell-depleted HLA non-identical bone marrow transplantation in the child:
      prevention of graft-versus-host reaction by administration of donor T lymphocytes
      alloreactive against the recipient].
AB  - The success of HSCT from HLA partially disparate donors depends on the
      development of new strategies able to efficiently prevent GVHD and to protect
      patients from infections and relapse. Using an immunotoxin (IT) directed against
      the alpha-chain (p55) of the human IL-2r (RFT5-SMPT-dgA), we have previously
      shown that it is possible to kill mature T cells activated towards a specific HLA
      complex by a one-way MLR. We designed a clinical trial assessing the effect of
      infusing increasing doses of T lymphocytes in the setting of children recipients
      of non HLA genetically identical HSCT. Thirteen patients have been enrolled from
      September 1998 to April 2000 and fourteen HSCT have been realized in 13 patients
      (pts). Donors were MUD in 3 cases and familial HLA partially disparate in the
      remaining cases. Allodepleted donor T cells were injected between day +14 and day
      +30 provided that ATG was undetectable in the serum and blood PMN counts was >
      500/microliter. The mean age of these patients was 17 months (range 1 to 42).
      Diagnosis included immune deficient and malignant hemopathies. Three patients
      received 1 x 10(5) allodepleted T cell/kg, 7 patients received 4 x 10(5)/kg and 4
      patients received 6 x 10(5)/kg allodepleted T cells. Full inhibition of MLR was
      achieved in 12 out of 14 cases. In two cases, a residual T cell reactivity to the
      recipient was observed (4 to 5%) and patients developed grade II aGVHD. aGVHD
      occurred in 4 out of 11 grafted patients (all grade II). No chronic GVHD has
      developed, so far. Three patients died from severe VOD or PHT at day +34, day 51
      and day +166, while one infected patient by VZV, CMV and EBV before HSCT died 6
      months after transplantation from meningoencephalitis and another patient died
      from relapse at day +291. The patient for which there was no engraftment died at
      day +48 from staphylococcus infection. Overall survival is 54%, with a median
      follow up of 8 months; the mean time to reach a blood lymphocyte count > 500 was
      41 days, to reach a CD3 count > 300 microliters 63 days (20-111), CD4 > 200
      microliters 97 days and positive mitogen-induced proliferation 90 days. In three
      patients, a tetanus-toxoid positive proliferation was detected before
      immunization. From this intermediate analysis, we conclude that 1) specific
      allodepletion is an effective approach to prevent aGVHD in a haploincompatible
      setting, 2) data on immunological reconstitution suggest that infused T cells do
      survive and expand. A higher number of patients must be enrolled to determine the
      optimal number of T cells to infuse.

PMID- 11530505
TI  - [Production of autologous keratinocytes for therapeutic purposes within a
      pharmaceutical company].
AB  - Because biotechnologies are growing and are becoming key players in the
      pharmaceutical industry scene, Genevrier Laboratories inaugurated in January
      1998, a new department especially designed for the production of cultured cells
      as therapeutic agents. Meeting clinician therapeutic needs by providing
      autologous keratinocytes and chondrocytes in the near future, represents the
      primary aim of the Biotechnology department. Concrete cell-based products are
      already being used for the treatment of burns and cutaneous chronic wounds such
      as the EPIBASE graft, which corresponds to an epidermis sheet composed of
      cultured autologous keratinocytes.

PMID- 11530506
TI  - [Cell therapy and its clinical applications. Cartilage cell therapy, present and
      future].
AB  - Articular cartilage has a very poor capacity for repair. In order to get a normal
      functional efficacy, the replaced tissue has to reproduce the structure,
      composition and physico-chemical properties of native cartilage tissue. The
      transplantation of cultured autologous chondrocytes into chondral defects is
      currently applicable only in the case of young sportive people with a limited
      lesion in an otherwise relatively normal joint. Recent experimental studies have
      shown that pluripotent mesenchymal cells from bone marrow could also repair
      experimental osteochondral defects. An advantage of this grafting procedure is
      that large areas of cartilage surface could be covered. Bone marrow cells are not
      so difficult to get, they have a high potency to divide and they can develop in
      vitro as chondrogenic, osteogenic or adipogenic cells. The present ways of
      research are: to characterize one or several growth factors capable to
      specifically induce the chondrogenic lineage; to determine nutrient and
      environmental conditions allowing the cultured chondrogenic cells to undergo a
      maturation process within the cell pellet; to elaborate three-dimensional
      synthetic, biodegradable polymeric scaffolds assessed with respect to
      chondrogenic cell adhesion, proliferation, maturation and cartilage matrix
      secretion; finally, to elaborate a mixed biomaterial composed of chondrogenic and
      osteogenic cells selectively distributed within polymeric scaffolds in order to
      get a better adherence of the implanted cells to the lesion sites.

PMID- 11530507
TI  - [Towards a cell therapy for diabetes? An epistemiological perspective].
AB  - This text describes, in an epistemological perspective, the development of the
      concept of cellular therapy applied to the treatment of type 1 diabetes. Emphasis
      is put on three recent papers describing the success of islet allograft in
      diabetic patients, the development of neo-islets from stem cells isolated from
      the pancreas of adult mice, and the effect of hepatic cell transfection with an
      adenovirus bearing the gene coding for PDX-1, a transcription factor involved in
      the maturation of islets of Langerhans. This text tries to delineate some factors
      which may be involved in the chances for these techniques to reach the real world
      of human therapeutics.

PMID- 11530508
TI  - [Chemokines and defense-system cell homing].
AB  - The general properties of chemokines and their receptors are described, and the
      perspectives raised for cellular therapy are discussed. Specific examples are
      provided in the cases of the CXC chemokine SDF1 and of chemokines ligands of
      CCR5.

PMID- 11530509
TI  - [The internal bioartifical liver].
AB  - A possible alternative to liver transplantation is the internal bioartificial
      liver (IBAL) consisting in the transplantation of isolated encapsulated
      hepatocytes. The goal of IBAL is to allow an auxiliary liver until native liver
      regeneration. The hepatocytes could be allogeneic or xenogeneic (animal origin).
      Large animal source of liver cells should allow immediate isolation of fresh
      hepatocytes when IBAL is required. The peritoneal cavity is probably the site of
      implantation of IBAL. In the future, IBAL could be envisioned as the treatment of
      metabolic deficiencies or acute and chronic liver failure. It could ensure a
      therapeutic bridge until transplantation.

PMID- 11530510
TI  - [The results of the 25 year work activities and prospects of the Research
      Institute for Complex Problems of Occupational Health and Occupational Medicine].

PMID- 11530511
TI  - [Specific aspects of the labor resources availability in the Kemerovo region
      under the conditions of unemployment].
AB  - Social and economic changes conducted by Russian authorities result in relatively
      uncommon for Russia phenomenon--unemployment that causes not only social crisis,
      but also considerable deterioration of public health.

PMID- 11530512
TI  - [Employment and health of compulsory migrants in a major industrial city of
      Siberia].
AB  - Medical and geographic contrasts, ecologically unfavorable conditions in some
      Eastern regions of Russia, dramatic social troubles in departure places and new
      residence of compulsory migrants not only result in acute diseases responding to
      stress situations, but also in exacerbation of chronic illnesses.

PMID- 11530513
TI  - [Medical and demographic evaluation of public health under the prolonged impact
      of specific ecological influences].
AB  - The materials represented cover medical and demographic study of public health
      state in Altai area, under prolonged exposure of certain populations to
      radioactive fallout due to nuclear testing at Semipalatinsk ground. The authors
      specified a method for retrospective medical and demographic diagnosis of the
      residents exposure to radioactive fallout caused by nuclear testing, for
      evaluation of consequent damage to public health.

PMID- 11530514
TI  - [The complex evaluation of risk factors at the thermoelectric power stations in
      Southern Kuzbass].
AB  - The authors conducted complex evaluation of health risk factors for heat power
      stations workers--that was a result of long studies specifying measures to
      optimize work conditions. The calculations covered the factors' biologic doses
      and critical length of service for various probabilities of occupational
      diseases.

PMID- 11530515
TI  - [The evaluation of risk factors for occupational diseases of miners in coal
      mines].
AB  - The article deals with hygienic evaluation of work conditions for open cast coal
      miners in Kouzbass. Based on the evaluation, the authors calculated occupational
      morbidity risk due to noise, local vibration, dust exposure. An occupational
      diseases index and hygienic criteria helped to specify general characteristics of
      occupational risk, measures of prophylaxis and social security for the main
      occupational groups of open cast coal miners in Kouzbass.

PMID- 11530516
TI  - [Genetic markers of occupational susceptibility to fluorosis].
AB  - To determine markers showing propensity to occupational fluorosis, the authors
      studied prevalence of ABO, Rh, MN, ABH and Lewis phenotypes, systemic rhesus
      haplotypes in 229 workers engaged into aluminum production. Propensity to
      occupational fluorosis was marked by P (+), O (ABO) phenotypes. P (-) phenotype
      appeared to be a marker of resistance to fluorides exposure. The results obtained
      could be useful to forecast probability of fluorosis and to better this disease
      prevention.

PMID- 11530517
TI  - [Oxygen and chiropractic therapy in the treatment of occupational hand
      neuropathies].
AB  - Efficient treatment for occupational compression neuropathy includes oxygen
      insufflation into diseased neural channel and subsequent chiropractic of joints
      and tissues, that form the channel.

PMID- 11530518
TI  - [Complex evaluation of the impact of emerging mining industries in Northern
      regions on public health].
AB  - The studies covered public health state in vicinity of concentration enterprise
      being built in Far North, with selecting a cohort of workers extracting diamonds
      in Yakutia, conducting a primary standardized health screening in accordance with
      WHO program. The public health state is characterized in connection with
      ecologic, social and economic circumstances. The authors necessitate complex
      evaluation of influence caused by industrial enterprises on health of workers and
      general population.

PMID- 11530519
TI  - [Morbidity risk for main aluminum industry occupations in Southern Kuzbass].

PMID- 11530520
TI  - [The model of information and analysis support for decision making processes in
      the optimization of municipal health care].

PMID- 11530521
TI  - [Risk assessment of vibration diseases among miners].

PMID- 11530522
TI  - [Altered states of consciousness among metal industry workers during night
      shifts].

PMID- 11530523
TI  - [Information servicing for the complex problems of social and occupational
      research].
AB  - Research directions set in 1976 on opening the Institute for Complex Problems of
      Hygiene and Occupational diseases with SD USSR AMSc in Novokuznetsk were based on
      new methodologic approaches. Fundamentals of the approaches are concept of life
      support, complex systemic attitude to social and hygienic research and to health
      care management--these are topical ones nowadays.

PMID- 11530524
TI  - [Determination of higher fatty acids in human plasma].
AB  - Methods for measurements of higher fatty acids in human blood are discussed. The
      possibility of using gas chromatography for this purpose is analyzed. Higher
      fatty acids were measured in the plasma of 56 elderly patients with noninsulin
      dependent diabetes mellitus and 17 age-matched healthy controls by gas
      chromatography. The concentrations of oleic and arachidonic acids were increased
      and that of myristic acid decreased in the diabetics vs. the controls.

PMID- 11530525
TI  - [Diagnostic significance of the cerebrospinal fluid protein spectrum in bacterial
      and viral meningitis in children].
AB  - Protein spectrum of the cerebrospinal fluid (CSF) was studied by polyacrylamide
      gel disk electrophoresis in 119 children with bacterial and 17 with viral
      meningitis of different origin over the course of disease. Liquor proteinograms
      of patients were compared with those of 37 children without meningitis. Protein
      spectra of the CSF were shifted in the patients. These shifts can serve as
      differential diagnostic markers: types 1-2 and 2-2 haptoglobins and beta
      lipoprotein appears in the blood during the acute period of disease. More
      pronounced and stubborn changes in the CSF protein spectrum in pneumococcal and
      hemophilic meningitis correlated with a more severe clinical course and formation
      of residual neurological consequences. Progress of dysproteinemic shifts in the
      protein spectrum of the CSF was characterized by a many-fold increase in the
      concentrations of high-molecular-weight proteins and decreased relative content
      of liquor-specific fractions, indicating sharp impairment of the blood-brain
      barrier permeability and formation of brain edema. Disk electrophoresis method is
      characterized by high resolution, informative value, requires low amounts of CSF
      for analysis, and is recommended as an accessory diagnostic test for infectious
      hospitals.

PMID- 11530526
TI  - [Lung neoplasms. Cytological diagnosis based on puncture biopsy specimens].
AB  - Twelve-year experience gained in cytological diagnosis of lung tumors by
      examining puncture biopsy specimens in 2536 patients is analyzed. The results
      indicate that before cytological verification of the diagnosis, patients with
      squamous-cell and glandular lung cancers were examined at various institutions
      for up to 6 months and patients with nondifferentiated cancer for up to 3 months,
      the majority (57%) patients being of socially active age (45-60 years). In 1793
      (70.7%) patients the cytological method was the only possibility of morphological
      interpretation of the pathological process in the lung before treatment. Analysis
      of informative puncture biopsy specimens helped identify the process in 2238
      (92.4%) patients. Cyto-histological correlations showed high diagnostic
      sensitivity (98.7%), efficiency (97.3%), and specificity (86.0%) of examining
      puncture biopsy specimens by the cytological method.

PMID- 11530527
TI  - [Cytological characteristics of Hodgkin disease with nodular sclerosis].
AB  - Cellular characteristics of tumor with nodular sclerosis verified histologically
      were retrospectively studied on puncture biopsy specimens of involved lymph nodes
      from 57 patients with cytologically verified Hodgkin's disease
      (lymphogranulomatosis). "Lacunar" cells in different combinations with three
      types (mononuclear, "mirror", and multinuclear) of Berezovskii-Sternberg cells
      and "reticular" cells were detected in 80.7% cases. The lymphoid component was
      presented by lymphocytes and prolymphocytes. Cell composition of the tumor in
      Hodgkin's disease with nodular sclerosis should be regarded as combination of
      tumor growth with reactive hyperplasia of the lymphoid tissue at the level of
      lymphocytes and prolymphocytes.

PMID- 11530528
TI  - [Information computer technologies--the timely and inevitable step in improvement
      of laboratory diagnosis (development and use of the automated working group
      "Hematology") (a lecture)].

PMID- 11530530
TI  - [Characteristics of erythrons in erythremia].

PMID- 11530529
TI  - [Detection of double bonds in serum blood lipids: titration by ozone,
      physiopathology, and diagnostic significance (a literature review)].

PMID- 11530531
TI  - [Limits of chromatographic determination of glycated hemoglobin (Hb A1c) in
      diabetes mellitus in presence of abnormal hemoglobins].
AB  - The content of glycated hemoglobin (Hb A1c) evaluated by high pressure
      chromatography on a VARIANT analyzer using Hb A1c software correlated with the
      mean daily blood glucose level in the majority of diabetics with types 1 and 2
      disease and helped evaluate the compensation of diabetes mellitus during the
      latest 2-3 months of observation. Low Hb A1c values in combination with an extra
      hemoglobin fraction, unidentified by the software we used, were detected in 3
      Russian women suffering from type 2 diabetes mellitus, with high blood glucose
      levels. Application of Hemoglobinopathy software showed an abnormal spectrum of
      hemoglobin fractions in the blood of all 3 patients: appearance of hemoglobin D
      paralleled by decrease of Hb A0. The presence of abnormal hemoglobin D in these
      patients was confirmed by the results of electrophoresis on cellulose acetate
      films and a negative test for sickle erythrocytes. Abnormal hemoglobins are
      responsible for discoordination between glucose content and Hb A1c in the blood
      of diabetics. Measurement of serum fructosamine is recommended for evaluation of
      diabetes compensation in patients with hemoglobinopathies.

PMID- 11530532
TI  - [Analysis of rheologic changes in blood based on a hemorheologic profile
      concept].
AB  - Changes in blood rheology were studied in 106 female hypertensive patients. Basic
      parameters of blood rheology were recorded: total blood viscosity, plasma
      viscosity, Hct, erythrocyte aggregation and deformability, fibrinogen,
      albumin/globulin ratio, and Hct/eta ratio. This set of parameters was presented
      as the hemorrheological profile. Blood and plasma viscosities were increased in
      hypertensive patients in comparison with the controls. Therapy with
      pentoxifylline (600-800 mg/day for 4 weeks) or angiotensin II receptor antagonist
      losatran (50 mg/day for 4 weeks) resulted in positive changes in the
      hemorrheological profile.

PMID- 11530533
TI  - [Interactions of hepatitis viruses B and C with the immune system cells in a
      macroorganism (a literature review)].

PMID- 11530534
TI  - [Optimization of a method of determination of circulating immune complexes of
      various size].

PMID- 11530535
TI  - [Mycobacterium tuberculosis detection by polymerase chain reaction and
      identification of M. tuberculosis strain].
AB  - A rapid multiprimer PCR method for detection of Mycobacterium tuberculosis
      complex (MTC) and simultaneous identification of M. tuberculosis in clinical
      samples has been developed. The method is based on simultaneous amplification of
      two targets: a 401 bp region from the mtp40 species-specific gene sequence of M.
      tuberculosis and a 544 bp fragment from the RD1 genome region which is specific
      for MTC but absent in BCG strains. Polymerase inhibitors in this study were
      detected by internal control in each test. Detection sensitivity was 25 copies of
      M. tuberculosis genomic DNA. Seven methods for isolation of mycobacterial DNA
      were compared and the technique with chloroform extraction was selected as the
      most efficient. The proposed method was used for analysis of 37 clinical samples
      and the results were compared with the results of culturing, acid-fast bacilli
      staining, and clinical diagnosis. The method proved to be sufficiently sensitive
      and specific for detection of mycobacterial DNA. Moreover, in countries with only
      two main pathogenic species of MTC circulating (M. tuberculosis and M. bovis)
      this method can be used for differentiation of these two species.

PMID- 11530536
TI  - [Application of "critical path" for management of quality of clinical laboratory
      analysis].

PMID- 11530537
TI  - [Clinical and diagnostic significance of serum angiotensin-converting enzyme
      activity determination].

PMID- 11530539
TI  - Heading to the point of no return. The e-supply chain is evolving, thanks to bold
      business moves and technology.

PMID- 11530538
TI  - Waste not, want not.

PMID- 11530540
TI  - Illuminating the conservation pathway.

PMID- 11530541
TI  - Glucosamine and chondroitin for osteoarthritis?
AB  - The current body of evidence currently supports modest efficacy for glucosamine
      and chondroitin in the treatment of OA symptoms. The products are safe and could
      play a valuable role in the management of this disorder. Nevertheless, further
      independent studies are needed to confirm these findings and to determine the
      clinical applicability of these compounds. Physicians need to become involved in
      these treatment decisions but are confused by wide variability in the formulation
      and purity of the numerous preparations available to consumers. The notion that
      glucosamine and chondroitin might have disease-modifying effects in OA is highly
      appealing and supported by preliminary data. Research is needed to confirm these
      findings and to evaluate the impact of glucosamine and chondroitin on all aspects
      of OA progression.

PMID- 11530542
TI  - On specification and the senses.
AB  - In this target article we question the assumption that perception is divided into
      separate domains of vision, hearing, touch, taste, and smell. We review
      implications of this assumption for theories of perception and for our
      understanding of ambient energy arrays (e.g., the optic and acoustic arrays) that
      are available to perceptual systems. We analyze three hypotheses about relations
      between ambient arrays and physical reality: (1) that there is an ambiguous
      relation between ambient energy arrays and physical reality, (2) that there is a
      unique relation between individual energy arrays and physical reality, and (3)
      that there is a redundant but unambiguous relation, within or across arrays,
      between energy arrays and physical reality. This is followed by a review of the
      physics of motion, focusing on the existence and status of referents for physical
      motion. Our review indicates that it is not possible, in principle, for there to
      be a unique relation between physical motion and the structure of individual
      energy arrays. We argue that physical motion relative to different referents is
      specified only in the global array, which consists of higher-order relations
      across different forms of energy. The existence of specificity in the global
      array is consistent with the idea of direct perception, and so poses a challenge
      to traditional, inference-based theories of perception and cognition. However, it
      also presents a challenge to much of the ecological approach to perception and
      action, which has accepted the assumption of separate senses.

PMID- 11530544
TI  - Culture in whales and dolphins.
AB  - Studies of animal culture have not normally included a consideration of
      cetaceans. However, with several long-term field studies now maturing, this
      situation should change. Animal culture is generally studied by either
      investigating transmission mechanisms experimentally, or observing patterns of
      behavioural variation in wild populations that cannot be explained by either
      genetic or environmental factors. Taking this second, ethnographic, approach,
      there is good evidence for cultural transmission in several cetacean species.
      However, only the bottlenose dolphin (Tursiops) has been shown experimentally to
      possess sophisticated social learning abilities, including vocal and motor
      imitation; other species have not been studied. There is observational evidence
      for imitation and teaching in killer whales. For cetaceans and other large, wide
      ranging animals, excessive reliance on experimental data for evidence of culture
      is not productive; we favour the ethnographic approach. The complex and stable
      vocal and behavioural cultures of sympatric groups of killer whales (Orcinus
      orca) appear to have no parallel outside humans, and represent an independent
      evolution of cultural faculties. The wide movements of cetaceans, the greater
      variability of the marine environment over large temporal scales relative to that
      on land, and the stable matrilineal social groups of some species are potentially
      important factors in the evolution of cetacean culture. There have been
      suggestions of gene-culture coevolution in cetaceans, and culture may be
      implicated in some unusual behavioural and life-history traits of whales and
      dolphins. We hope to stimulate discussion and research on culture in these
      animals.

PMID- 11530543
TI  - Developmental structure in brain evolution.
AB  - How does evolution grow bigger brains? It has been widely assumed that growth of
      individual structures and functional systems in response to niche-specific
      cognitive challenges is the most plausible mechanism for brain expansion in
      mammals. Comparison of multiple regressions on allometric data for 131 mammalian
      species, however, suggests that for 9 of 11 brain structures taxonomic and body
      size factors are less important than covariance of these major structures with
      each other. Which structure grows biggest is largely predicted by a conserved
      order of neurogenesis that can be derived from the basic axial structure of the
      developing brain. This conserved order of neurogenesis predicts the relative
      scaling not only of gross brain regions like the isocortex or mesencephalon, but
      also the level of detail of individual thalamic nuclei. Special selection of
      particular areas for specific functions does occur, but it is a minor factor
      compared to the large-scale covariance of the whole brain. The idea that enlarged
      isocortex could be a "spandrel," a by-product of structural constraints later
      adapted for various behaviors, contrasts with approaches to selection of
      particular brain regions for cognitively advanced uses, as is commonly assumed in
      the case of hominid brain evolution.

PMID- 11530545
TI  - Walk-in centres. On the wrong foot?

PMID- 11530546
TI  - Health centres. The estate we're in.

PMID- 11530547
TI  - Health policy. Honour bound.
AB  - The government should sort out the inconsistencies in its health policies. NHS
      managers have a good record on implementing government policy. The health
      secretary needs to clarify his attitude to managers and address the loss of top
      people.

PMID- 11530548
TI  - Information services. Read between the lines.

PMID- 11530549
TI  - Sexual health. Chasing shadows.

PMID- 11530550
TI  - [Contraception].

PMID- 11530551
TI  - [Chlamydia. Time for screening of sexually active young people?].

PMID- 11530552
TI  - [Contraception in Denmark in 2000].

PMID- 11530553
TI  - [Barrier methods of contraception].

PMID- 11530554
TI  - [Intrauterine contraceptive device].

PMID- 11530555
TI  - [Oral contraceptives. General aspects].

PMID- 11530556
TI  - [Oral contraceptives to women which run special risks].

PMID- 11530557
TI  - [Oral contraceptives and thrombosis].

PMID- 11530559
TI  - [Sterilization].

PMID- 11530558
TI  - [Hormonal contraception with gestagens].

PMID- 11530560
TI  - [Contraception in future: research and clinical possibilities].

PMID- 11530561
TI  - [Toll-like receptors. What can we learn about the immune system from banana flies
      and a mouse strain].

PMID- 11530562
TI  - [Irritable colon].
AB  - Irritable bowel syndrome is a chronic, relapsing functional bowel disorder of
      unknown aetiology. Methods of studying intestinal motor function, nociception,
      and interactions of the central nervous system and enteric nervous system are not
      applicable for clinical use. The diagnosis is therefore made on the symptoms, but
      it is necessary to exclude relevant organic disease. Establishment of the
      diagnosis, information about the disorder, elimination of foods and other factors
      that provoke the symptoms, and a change in life-style are sufficient in most
      cases. Treatment is hampered by the lack of effective treatment and the
      psychological aspects. The therapeutic gain of drug administration is modest and
      the rate of response to placebo is high. Fibre supplementation, magnesium oxide
      or cisapride may be tried for constipation, diphenoxylate or loperamide for
      diarrhoea, and low dose tricyclic antidepressants or serotonin reuptake blockers
      for severe pain. The introduction of 5-hydroxytryptamine-3 (5-HT3) receptor
      antagonists seems promising.

PMID- 11530563
TI  - [Antibiotic treatment of travellers' diarrhea].
AB  - This review should be cited as: De Bruyn G, Hahn S, Borwick A. Antibiotic
      treatment for travellers' diarrhoea (Cochrane Review). In: The Cochrane Library,
      Issue 1, 2001. Oxford: Update Software. A substantive amendment to this
      systematic review was last made on 21 May 2000. Cochrane reviews are regularly
      checked and updated if necessary. BACKGROUND: Traveller's diarrhoea is a syndrome
      frequently encountered in persons crossing an international boundary. Diarrhoea
      can lead to significant discomfort and interference with travel plans. Bacterial
      pathogens are a frequent course of this syndrome. Several antibiotics have been
      tested for efficacy in reducing the duration and severity of the illness.
      OBJECTIVES: The aims of the review were to access the effects of antibiotics on
      traveller's diarrhoea in relation to the duration of illness, severity of
      illness, and adverse effects of medications. SEARCH STRATEGY: The Cochrane
      Collaboration Trials Register, MEDLINE, and EMBASE were searched. Additional
      trials were identified by hand searching. Content experts were contacted.
      SELECTION CRITERIA: All trials in any language in which travellers older than
      five years were randomly allocated to treatment for acute non-bloody diarrhoea
      with antibiotics and where the causative organism is not known at allocation.
      DATA COLLECTION AND ANALYSIS: Two reviewers assessed trial quality and extracted
      data. MAIN RESULTS: Twenty published studies met inclusion and quality criteria
      for inclusion. Twelve studies were placebo-controlled. A meta-analysis for the
      primary outcome was not feasible. All of the ten trials reported a significant
      reduction in duration of diarrhoea in participants treated with antibiotics
      compared with placebo. Data from two trials demonstrated a small reduction for
      antibiotic treated patients in the number of unformed stools passed per each 24
      hour period from randomisation up to 72 hours. Data from six trials demonstrated
      a greater number of participants being cured of diarrhoea by 72 hours (odds ratio
      [OR] 5.9, 95% confidence interval [CI] 4.06 to 8.57). Data regarding side effects
      were available from five trials. There was wide variation in the prevalence of
      side effects reported in different trials. Persons taking antibiotics experienced
      more side effects than those taking placebo (OR 2.37, 95% CI 1.5 to 3.75).
      REVIEWERS' CONCLUSION: Antibiotic treatment is associated with shorter duration
      of diarrhoea but higher incidence of side effects. Trials generally do not report
      duration of post-treatment diarrhoea using time-to-event analyses, and should do.

PMID- 11530564
TI  - [Insertion of intrauterine device in general practice. Which women choose the
      IUD, and how is the procedure done?].
AB  - INTRODUCTION: In Denmark most IUDs are inserted by general practitioners (GPs).
      The aim of this study was to throw light on which women choose IUD, the procedure
      used, and difficulties associated with insertion. MATERIAL AND METHODS: All 232
      GPs in Frederiksborg County were invited to participate and 88 agreed. The GP
      filled in a questionnaire concerning the type of IUD, the age, parity, etc, of
      the woman and information about the insertion. RESULTS: Eighty-eight GPs
      contributed with 562 IUD insertions. IUD was mostly used by women above 25 years
      of age and by women who had given birth to a child. There were no differences in
      the insertion procedures used by the doctors. Fifty-nine per cent of the women
      were previous IUD users. Of the former users, 37% reported problems with the
      previous use of the IUD. Twenty-five per cent of the women in this study reported
      that they had had heavy or long-lasting menstruation before insertion. Fifty-five
      per cent of the women had a test for chlamydia before insertion. Twenty-three
      (4.1%) insertions were abandoned. 26 (4.6%) insertions were described as
      difficult. The highest frequency was in women using gestagen-releasing IUDs.
      CONCLUSION: IUD was mainly used by women, who had given birth to a child. The
      gestagen releasing IUD was mostly used by the elder group and by women with heavy
      bleedings before insertion. The procedure was very identical and the number of
      abandoned and difficult insertions were low and only related to the type of IUD.
      More female than male doctors participated. Doctors working in partnerships
      participated more frequently than doctors working alone.

PMID- 11530565
TI  - [Does alcohol increase the risk of preterm delivery?].
AB  - INTRODUCTION: The aim was to assess the association between alcohol intake during
      pregnancy and preterm delivery. MATERIALS AND METHODS: Women attending routine
      antenatal care at Aarhus University Hospital, Denmark, from 1989-1991 and 1992
      1996 were eligible for the study. Our analyses included 18,228 singleton
      pregnancies. We obtained prospective information on alcohol intake at about 16
      and 30 weeks of gestation, other lifestyle factors, maternal characteristics, and
      obstetrical risk factors from questionnaires completed by the women and hospital
      files. RESULTS: For women with an alcohol intake of 1-2, 3-4, 5-9, and > or = 10
      drinks/week, the risk ratio (RR) of preterm delivery was 0.91 (95% CI: 0.76
      1.08), 0.86 (0.64-1.15), 0.89 (0.52-1.52), and 2.93 (1.52-5.63) respectively,
      compared with an intake of < 1 drink/week at about 16 weeks of gestation, and
      0.69 (0.56-0.86), 0.82 (0.60-1.13), 0.97 (0.58-1.64), and 3.56 (1.78-7.13) at
      about 30 weeks. Adjustment for smoking habits, caffeine intake, age, height,
      prepregnant weight, marital status, occupational status, education, parity,
      chronic diseases, previous preterm delivery, mode of initiation of labour, and
      sex of the child did not alter the conclusions, nor did restriction of the
      highest intake group to women drinking 10-14 drinks/week (RR = 3.41 (1.71-6.81)
      at 16 weeks and RR = 3.47 (1.64-7.35) at 30 weeks). DISCUSSION: The association
      between alcohol intake and preterm delivery appeared to be J-shaped, with a
      threshold for adverse effect at a level of about 10-14 drinks/week.

PMID- 11530566
TI  - [Prevalence of Chlamydia among young men. A screening among men liable for
      military service and coming before the military board].
AB  - INTRODUCTION: Chlamydia is the most common sexually transmitted bacterial
      infection in Denmark. Each year 13-14,000 cases are diagnosed; of these about
      3000 occur in men. In order to describe the prevalence of chlamydia among young
      men, screening for chlamydia was conducted in those liable for military service
      and coming before the medical board. MATERIALS AND METHODS: Of 2500 men coming
      before the medical boards in North Jutland State County, Arhus State County, and
      Copenhagen County during the winter of 1996-97, 1345 men aged 17-32 (median 18
      years) were entered in the study. The participants sent a urine sample and a
      filled-in questionnaire to Statens Serum Institut. The urine samples were
      analysed by an in-house PCR and the test results were sent to the participant; if
      permission had been granted, the positive test results were further sent to the
      general practitioner, along with a second questionnaire. RESULTS: Chlamydia was
      found in 4.8% (65/1345) of all participants and in 6.9% of those sexually active.
      In North Jutland State County 7.1 and 9.8%, respectively, had chlamydia, whereas
      the corresponding figures for Arhus State County and Copenhagen County were about
      4% and 6%. Two-thirds of the patients had no symptoms of urethritis. DISCUSSION:
      The results of this study indicate that a considerable reservoir of unrecognised
      chlamydia must exist in young men. The prevalence of chlamydia was higher in
      North Jutland State County than in the other two districts. One explanation could
      be that there is more focus on sexually transmitted infections and contact
      tracing in the largest cities than in the rest of the country.

PMID- 11530567
TI  - [Handling of Chlamydia infections in young men aged 15 to 25 years by general
      practitioners. A questionnaire study].
AB  - INTRODUCTION: Urogenital chlamydia is still common in the young. The late risks
      are well-documented. Most of the infections are diagnosed in general practice.
      The aim was to assess general practitioners' handling of urogenital chlamydial
      infections in young people aged 15-25 years. METHODS: Two groups of GPs were
      selected at random and were asked to complete a questionnaire before and after a
      "State-of-the-Art" was sent to all GPs from the National Board of Health. The
      questionnaire covered questions about 1) the test indication; 2) advice on the
      infection diagnosed; 3) contact tracing; and 4) first choice of treatment for
      uncomplicated infection in non-pregnant women. RESULTS: There was no difference
      between the two groups in the answers to questions 1) to 3), but an obvious
      change towards single-dose treatment in question 4), not because of the "State-of
      the-Art", but rather because of the intensive marketing of the simple treatment
      regime. DISCUSSION: Implementation of new knowledge in general practice does not
      work only through national guidelines from the authorities to general practice,
      but is wholly dependent on central and local collaboration and GPs having the
      chance to discuss it between themselves.

PMID- 11530568
TI  - [Neonatal submandibular sialadenitis].
AB  - Submandibular sialadenitis is very rare in the neonatal period. Only a few cases
      have been reported of isolated submandibular gland infection without the
      involvement of the parotid gland. In the present case, a premature boy, fourteen
      days old, developed clinical signs of infection and bilateral submandibular
      erythematous swelling. Pus was expressed from the submandibular ducts. Culture
      yielded Staphylococcus aureus. He was treated with intravenous netilmicin and
      cefuroxin. The infection resolved after antibiotic therapy.

PMID- 11530569
TI  - [Hyperhomocysteinemia and hypothyroidism].
AB  - Moderate hyperhomocysteinaemia is associated with hypothyroidism. Increased
      levels of homocysteine might contribute to a greater cardiovascular risk. This
      paper reports a case of transient myxoedema, owing to postpartum thyroiditis. The
      fluctuation of P-homocysteine was inversely correlated to the free thyroxine
      index. We recommend TSH screening of patients with unexplained
      hyperhomocysteinaemia.

PMID- 11530570
TI  - [Two cases of B-cell disease coexisting with acromegaly].
AB  - The first two Danish cases of a B cell disease co-existing with acromegaly are
      reported, although over the last twelve years similar cases have been reported
      worldwide. We can only conclude that acromegaly might predispose to B cell
      diseases and therefore it is still important to report new cases. It is relevant
      to consider acromegalic patients as having an elevated risk of developing such
      diseases. Any signs of acromegaly should be taken seriously in patients with B
      cell diseases. We also suggest that abuse of GH, as seen in certain sports, may
      increase the risk of developing malignant B cell diseases.

PMID- 11530571
TI  - [Is measurement of the release of cerebral neurotransmitters possible?].

PMID- 11530572
TI  - [Foot problems].

PMID- 11530573
TI  - [Human albumin, a possible way of transmission of prion disease].

PMID- 11530574
TI  - [Global strategy when it comes to chronic obstructive lung disease].

PMID- 11530575
TI  - [Teacher among physicians or "foreigner among natives"].

PMID- 11530576
TI  - [Recurrence of depression caused by pharmacies].

PMID- 11530577
TI  - [Renewal of driver's licence: licence suspended for two of five "possibly
      demented" drivers].

PMID- 11530578
TI  - [Revised guidelines for long-term oxygen inhalation therapy].

PMID- 11530579
TI  - [Propofol anesthesia or pure gas?].

PMID- 11530580
TI  - [Nausea and vomiting after propofol anesthesia].

PMID- 11530581
TI  - Tumour markers in ovarian cancer.

PMID- 11530582
TI  - Handling clinical negligence claims: implications for the NHS.

PMID- 11530584
TI  - Update on leprosy.
AB  - Leprosy, a result of infection by Mycobacterium leprae, is a leading cause of
      peripheral neuropathy. The World Health Organization aimed to eliminate leprosy
      as a public health problem by 2000, but this has not been attained. Patients with
      leprosy continue to present in the UK. The diagnosis of leprosy is frequently not
      considered, with resultant pathological and psychological problems for patients.

PMID- 11530585
TI  - The use of botulinum toxin in ophthalmology.
AB  - As the diversity of clinical applications for the botulinum neurotoxin continues
      to grow, exciting developments are occurring in its use around the eye, where
      indeed its benefits were first recognized. These include use to treat strabismus,
      eyelid disorders and a number of other ocular conditions.

PMID- 11530583
TI  - Updated guidelines for the management of Parkinson's disease.
AB  - New data on diagnosis, drug therapy, surgery and psychosocial concerns have
      emerged since the publication of the 1998 Guidelines for the Management of
      Parkinson's Disease. This article reviews new data and addresses issues left
      unanswered in the previous guidelines.

PMID- 11530586
TI  - Recent advances in neuroanaesthesia.
AB  - In order to provide optimum intracranial operating conditions for neurosurgery,
      anaesthetists must have a thorough understanding of brain physiology and how this
      is affected by pathology and anaesthetic drugs and techniques. This article
      discusses the current understanding of cerebral vascular physiology and how novel
      neuroanaesthetic drugs and techniques affect it.

PMID- 11530587
TI  - Overview of restless legs syndrome.
AB  - Restless legs syndrome is a common movement and sleep disorder, which can
      significantly reduce quality of life. Restless legs syndrome is probably related
      to dopamine imbalance and may have a primary or secondary aetiology. It is
      greatly underdiagnosed, yet potentially treatable.

PMID- 11530588
TI  - Colorectal cancer surveillance post-surgery.
AB  - Current surveillance methods for detecting recurrence after apparently curative
      colorectal cancer resection are insensitive and have not been shown to
      significantly improve survival. New surveillance methods based on molecular, flow
      cytometric and immunohistochemical detection of small numbers of tumour cells may
      prove more sensitive in detecting early recurrent cancer and may improve outcome.

PMID- 11530589
TI  - Producing a multimedia CD-ROM.
AB  - The multimedia capabilities of modern computers promise a rich contribution to
      medical education, integrating video, animation and graphics as a single
      courseware package. Using the new generation of design tools, computer-assisted
      learning material can be successfully created in-house.

PMID- 11530590
TI  - Case 5: cardiac memory.

PMID- 11530591
TI  - Stress in hospital medicine: a problem for key hospital staff.
AB  - Many factors which contribute to stress in the workplace apply to both
      consultants and ward sisters. Both groups find that their roles have become more
      complex while they have increasingly lost control of their own clinical and
      professional territory in a managerial culture. The erosion of the key
      relationship between consultants and ward sisters is of concern and the need for
      teamworking is insufficiently recognized.

PMID- 11530593
TI  - Implications of interscalene brachial plexus block in the elderly patient.

PMID- 11530592
TI  - Vertebral artery dissection secondary to prolonged telecommunication.

PMID- 11530594
TI  - Serendipitous computed tomographic diagnosis of an underlying cause for diabetes
      mellitus.

PMID- 11530595
TI  - Redefining myocardial infarction.

PMID- 11530596
TI  - Redefining myocardial infarction.

PMID- 11530597
TI  - Redefining myocardial infarction.

PMID- 11530598
TI  - Ascitic fluid analysis: the role of imaging.

PMID- 11530599
TI  - Should the neutropenic patient with respiratory failure be ventilated?

PMID- 11530600
TI  - Strategies for rescuing plasmid DNA from yeast two-hybrid colonies.

PMID- 11530601
TI  - Two-hybrid system and false positives. Approaches to detection and elimination.

PMID- 11530602
TI  - Confirming yeast two-hybrid protein interactions using in vitro glutathione-S
      transferase pulldowns.

PMID- 11530603
TI  - Media formulations for various two-hybrid systems.

PMID- 11530604
TI  - Two-hybrid interactions confirmed by coimmunoprecipitation of epitope-tagged
      clones.

PMID- 11530605
TI  - Smad interactors in bone morphogenetic protein signaling.

PMID- 11530606
TI  - Protein interactions important in eukaryotic translation initiation.

PMID- 11530607
TI  - Steroid receptor and ligand-dependent interaction with coactivator proteins.

PMID- 11530608
TI  - Interaction of cellular apoptosis regulating proteins with adenovirus anti
      apoptosis protein E1B-19K.

PMID- 11530610
TI  - One-hybrid systems for detecting protein-DNA interactions.

PMID- 11530609
TI  - Mammalian two-hybrid assays. Analyzing protein-protein interactions in
      transforming growth factor-beta signaling pathway.

PMID- 11530611
TI  - The split-hybrid system. Uncoding multiprotein networks and defining mutations
      that affect protein interactions.

PMID- 11530612
TI  - Three-hybrid screens. Inducible third-party systems.

PMID- 11530613
TI  - Three-hybrid screens for RNA-binding proteins. Proteins binding 3' end of histone
      mRNA.

PMID- 11530614
TI  - The two-hybrid system. A personal view.

PMID- 11530615
TI  - Membrane recruitment systems for analysis of protein-protein interactions.

PMID- 11530616
TI  - Yeast two-hybrid vectors and strains.

PMID- 11530617
TI  - High-efficiency transformation of plasmid DNA into yeast.

PMID- 11530618
TI  - Growth and maintenance of yeast.

PMID- 11530619
TI  - Qualitative and quantitative assessment of interactions.

PMID- 11530620
TI  - Two-hybrid systems. Methods and protocols. Introduction.

PMID- 11530621
TI  - Going outside the box: finding new ways to provide quality care to children and
      adolescents.
AB  - When it comes to providing better health care for children and teens, sometimes
      the health care system need to go outside the box and consider cutting across
      other settings such as schools, homes, and community organizations. This means
      that health care leaders need to keep goals in mind--to incorporate more
      approaches such as talking to teens about issues such as safe sex, smoking, or
      drinking or to improve ways to provide appropriate care at opportune times.

PMID- 11530622
TI  - AHRQ issues critical analysis of patient safety practices.
AB  - A new evidence report/technology assessment on patient safety from the Agency for
      Healthcare Research and Quality (AHRQ) lists and evaluates 73 practices aimed at
      improving patient safety nationwide. The report, Making Health Care Safer: A
      Critical Analysis of Patient Safety Practices, is an attempt to "bridge what we
      need to know about patient safety and what we now know about patient safety,"
      says AHRQ Administrator John Eisenberg, MD.

PMID- 11530623
TI  - [Sanitary assessment of the microclimate of suburban rolling stock].

PMID- 11530624
TI  - [Evaluation of medical X-ray radiation in the population of the Ryazan region].

PMID- 11530625
TI  - [Development of opportunistic microorganisms in the area of disposal of heated
      waters from atomic power stations].
AB  - Long-term studies conducted on cooling water reservoirs of the Kursk, Kalinin,
      and Smolensk atomic power stations have indicated that disposal of heated waters
      causes a considerable increase in the water count of opportunistic
      microorganisms. Possible factors that promote the increased number of these
      bacteria. The paper shows it necessary to perform microbiological studies of not
      only water lands of cooling water reservoirs, but of the inner surface of
      technical units of the water supply systems of an atomic power stations where
      favourable conditions may be created for the opportunistic and pathogenic
      microflora to develop.

PMID- 11530626
TI  - [Content of asbestos fibers in water sources of the Bazhenovo deposit].
AB  - The paper provides preliminary measurements of asbestos levels in water sources
      from an area of the Bazhenovo chrysotile-asbestos deposit. All study water
      samples have been found to contain chrysotile-asbestos fibers at concentrations
      one-three orders less that the values standardized in the USA (7 x 10(6) vol/l).
      The authors consider it advisable to continue studies to measure asbestos levels
      in the water sources in the areas in vicinity of other Russian deposits.

PMID- 11530627
TI  - [Effects of phenoxy carboxylic acid herbicides on plant photosynthetic and soil
      microbiological activities].
AB  - Lontrele and cowboy were tested for effects on the photosynthetic activity of
      amaranthus and the microbiological activity of leached chernozem. The tested
      herbicides were shown to be beneficial for different changes occurring in the
      levels of total chlorophyll in the amaranthus leaves and for the leached
      chernozem to evolve carbon dioxide in different phases of amaranthus growth.

PMID- 11530628
TI  - [Sanitary characteristics of chemical risk factors under conditions of housing
      environment].

PMID- 11530629
TI  - [Forecast of the sanitary status of the Ivankovo water reservoir in the area
      exposed to the Konakovo hydrostatic power station].

PMID- 11530631
TI  - [Medical and demographic assessment of human health under conditions of radiation
      and toxic exposures].
AB  - Medical and demographic assessments of the impact of a complex of man-made and
      radiation exposures on the population of the Altai territory revealed that the
      use of retrospective diagnosis of radiation exposures of Semipalatinsk ground
      testing and the account of additional exposures to combined effects of dioxines,
      heavy metals, rocket fluel components (heptyl, etc.), which are observed in
      specially identified former administrative areas of this territory in causing
      specific changes in the health status of neonates, pregnant females, and able
      bodied individuals are of priority in sociosanitary monitoring of sanitary and
      epidemiological service.

PMID- 11530630
TI  - [A complex of informative indices of adaptive and compensatory mechanisms for
      individual prognostication of occupational hypoacusis upon exposure to noise in
      combination with vibration and dust].
AB  - A differential diagnostic complex of 11 physiological, anthropometric, and
      biochemical parameters of most informative value that reliably (over 98%
      reliability) characterize the status of adaptive and compensatory mechanisms upon
      exposure to in-plant noise in combination with local and total vibration, and
      dust in terms of individual noise sensitivity. Testing the proposed procedure
      showed its high accuracy to define the terms "exhaustion" and "normal" specific
      adaptation, high (81.2%) significance of individual (5-year) prediction of
      occupational hypoacusis, an 50%-increase in detection rates of risk groups among
      workers. The procedure developed is recommended to use in regular professional
      surveys for specific adaptation, individual prediction and detection of early
      disorders, to enhance the accuracy of diagnosis of occupational hypoacusis, to
      employ in professional selection, to define the allowable time of labour
      activity, and to make priority. The proposed procedure defended by copyright has
      been introduced into practice.

PMID- 11530632
TI  - [Computer display color combinations and symbols that provide the optimum visual
      working capacity of an operator].
AB  - While working with displays, a combination of white and yellow objects against
      the black, dark grey, and blue backgrounds was found to be the best in
      visibility. When the objects were observed against the pale grey and green
      backgrounds of a display, eye functional changes were minimal, which causes the
      authors to recommend them as the optimum backgrounds. To reduce visual
      fatigability when a person works on a computer requires to alternate backgrounds
      by using white and yellow objects against the black and blue backgrounds for
      short-term emergency transmissions and green and pale grey backgrounds for
      presenting continuous current information.

PMID- 11530633
TI  - [Effects of vibration on contents of micronuclei in polychromatophilic
      erythrocytes of the rat bone marrow].
AB  - The paper presents data on the impact of vibration (32 Hz) on spontaneous
      mutagenesis in mammals. Higher counts of micronuclei were found in the bone
      marrow polychromophilic red blood cells in rats on day 5 of exposure to
      vibration, there was a reduction in their counts by day 20 and their recovery by
      day 30, and their steady-state decrease within 30 days after vibration
      discontinuation. The involvement of emotional stress in the mechanism of
      antimutagenic action of vibration is considered.

PMID- 11530634
TI  - [Clinical and epidemiological manifestations of acute viral hepatitis in workers
      of chemical industry enterprises].
AB  - The paper presents epidemiological and clinical findings in patients with acute
      viral hepatitis A, B, or C, whose occupation is associated with the entrance of
      chemicals into the working area air. Patients who are not engaged in chemical
      industry are a control group. It has been found that adults who had adverse
      working conditions show an intensified epidemic process of acute viral hepatitis
      and a more aggravated infectious process. It is necessary to regard workers at
      chemical industrial enterprises as a risk group who will have more severe acute
      viral hepatitis of different etiology.

PMID- 11530635
TI  - [Physical development and health of children of polyurethane foam plant workers].
AB  - The paper presents data on poor working conditions at the foam polyurethane (FPU)
      plant, which cause specific clinical manifestations in workers, indirectly exert
      their children's health. The children of FPU plant workers have lower physical
      development, diseases of immune genesis (glumeronephritis, bronchial asthma,
      allergic manifestations, etc.) more frequently, higher incidence of dental
      caries, enamel hypoplasia in the presence of altered mineral metabolism.

PMID- 11530636
TI  - [Problems in improvement of working conditions in rolling stock and railroad
      workers].

PMID- 11530637
TI  - [Sanitary characteristics of working conditions in vegetable growing places in
      the Republic of Tatarstan].
AB  - The paper gives a sanitary characterization of working conditions in closed soil
      vegetable growing, a branch of agriculture. These conditions are one of the
      factors predisposing to occupational disease in agricultural workers. Studies in
      this area may evaluate the risk of occupational diseases.

PMID- 11530638
TI  - [Prevention of gynecologic diseases in women students of higher educational
      institutions].
AB  - Menstrual function and gynecologic morbidity were studied in 4202 female students
      from medical, engineering, and chemical institutes. They were found to have
      algomenorrhea, ovary dysfunction, algo-hyper-polymenorrhea, hyper-polymenorrhea.
      Among genital inflammations there were predominant erosion of the cervix uteri,
      adnexitis, and colpitis. After therapeutical and conditioning measures the vast
      majority of girls convalesced.

PMID- 11530639
TI  - [Psychosocial dysadaptation in students with chronic somatic diseases].
AB  - To reveal the specific features of psychosocial adaptation in students having
      chronic somatic diseases, 114 students from the humanitarian faculties of the
      Pomor State University of Arkhangelsk were examined. Among them, 65.79% of the
      students had chronic somatic diseases, 34.21% had no diseases or complaints. The
      examination was made at the session interval. The students with chronic somatic
      diseases had a more significant psychosocial dysadaptation, which is indicative
      of higher depression and anxiety, timidity, reticence, lower activity,
      understated self-assessment, lower self-esteem, noticeable discord of personal
      relations. The paper shows it necessary to follow up emotional features of health
      within the framework of the regional programme "Students' Health" that includes
      the development of therapeutical, rehabilitative, and preventive measures.

PMID- 11530640
TI  - [Evaluation of the tension of regulatory mechanisms in schoolchildren in the
      North].
AB  - The regulatory mechanisms were evaluated in healthy first-former pupils living in
      the North by using cardiointervalography and calculating basic parameters that
      reflect the specific features of cardiac rhythm regulation. This revealed various
      tension of the regulatory systems that characterize a different "cost of
      adaptation" in the examinees to environmental conditions. The optimum status in
      most children is maintained by a high "physiological cost", significant tension
      and occasionally overstrain of their regulatory mechanisms, which may predispose
      to diverse diseases.

PMID- 11530641
TI  - [Age-specific features of the movement control system in young schoolchildren].
AB  - Analyzing spatial, temporary, and strength characteristics of movements in 7-10
      year-old children by using a graphoanalytical method during the reverse exercise
      test has indicated that overstrain occurs in all units of the structures that
      ensure formation and implementation of a transitional process. There are
      increases in regulation errors by 33%, regulation time by 21.5%, system
      variability by 16%, regulation stability by 19%. The variability of the system is
      beyond three fluctuations, which is an indicator of full transition of the
      movement control system in unreliability and instability. The investigations have
      demonstrated that the reverse exercise procedure is adequate to age-related
      features of children and may be useful in studying different functional systems.
      The graphoanalytical method of quantitative assessment of the functional status
      of the locomotor apparatus is of rather informative value and can be used in the
      professional activities of a teacher and trainer for personal assessment of the
      movement control system in children of different age.

PMID- 11530642
TI  - [Microsomal monooxygenases upon inhalation exposure to pseudocumene and durene].
AB  - This paper gives data on the levels of cytochromes of B5, P450, P420, P450 +
      P420, on the rates of amidopyrinum N-demethylation and aniline n-hydroxylation in
      the tissues of the lung, liver, kidney of experimental rats upon acute and
      chronic (4-month) inhalation exposure to pseudocumol and durol at a concentration
      of 10 mg/m3. Acute and chronic inhalation exposures to the xenobiotics in this
      concentration result in activation of microsomal monooxygenases in the tissues of
      experimental rats in relation to the type of exposure.

PMID- 11530644
TI  - [Aspects of industrial toxicology in contact with mineral fertilizers in railway
      transport].

PMID- 11530643
TI  - [Activity of digestive enzymes during intraperitoneal intake of metal compounds].
AB  - Digestive function was studied when three compounds from Group VIB of the
      Mendeleev periodic system of elements were intraperitoneally administered during
      100 days. Potassium bichromate, ammonium molybdate in a dose of 0.2 mg/kg and
      sodium tungstate in a dose of 5.0 mg/kg (in terms of metal) were found to have a
      resorptive effect on pancreatic function and a local effect on the small
      intestinal mucosa.

PMID- 11530645
TI  - [Hydromethylnon baits as means of cockroach and ant control].

PMID- 11530646
TI  - [Organization of investigations and evaluation of health risk in modern
      epidemiology].

PMID- 11530647
TI  - ["Health-environment" monitoring].

PMID- 11530648
TI  - [Monitoring of morbidity and demographic indices].

PMID- 11530649
TI  - [Health problems of the urbanized North (review)].
AB  - Industrial development of northern areas has caused changes in sociosanitary
      working and living conditions of the population. The indices of public health
      have become an integral criterion for the environmental situation. A complex
      approach must be used for ecological and sanitary assessments of the environment.
      Technogenic stress has lead to the appearance of adverse environmental factors
      against which the human body has produced no adaptive mechanisms; they may
      contribute to the development of virtually all diseases. The specific features of
      the North do not allow the experience accumulated in other regions of the country
      to be mechanically extended there. To lower the environmental concentration of
      pollutants will be beneficial to human health.

PMID- 11530650
TI  - [Approaches to estimating man-made burden on an area in terms of basic indices of
      population health].

PMID- 11530651
TI  - [Environmental air benzene levels in different districts of Tallin].

PMID- 11530652
TI  - [Use of ECHO gas chromatograph in sanitary service].

PMID- 11530653
TI  - [Evaluation of mental state in a contingent during health studies].

PMID- 11530654
TI  - [Sanitary assessment of a new ShKID-type isolating respiratory apparatus].

PMID- 11530655
TI  - [Evaluation of current methods and equipment used to detect components of
      petroleum and its products in the air].

PMID- 11530656
TI  - Demo produces stunning results in care of complex patients.

PMID- 11530657
TI  - 'Behavior change' is centerpiece of new DM approach for diabetics.
AB  - An unprecedented study suggests that focusing solely on behavior may, in fact, be
      a valid way to go when designing an intervention for type 1 and type 2 diabetics.
      In this study, researchers used a behavioral intervention specifically targeted
      at three diabetes-related behaviors. And participants not only made strides with
      respect to the targeted behaviors, but these changes also translated into
      clinical improvements as measured by HbA1c levels.

PMID- 11530658
TI  - Researchers find new value in group visit concept among chronically ill adults.
AB  - Pioneered more than 10 years ago for the care of chronically ill seniors, the
      group-visit concept for primary health care delivery has been tried in numerous
      settings with varying degrees of success. However, with more experience,
      clinicians today have a better idea of how to most effectively deliver this form
      of care--in some cases producing solid financial returns and a high degree of
      patient satisfaction. New data shows just how valuable the concept can be when
      applied to chronically ill seniors.

PMID- 11530659
TI  - New effort highlights dangers associated with nighttime symptoms of GERD.
AB  - Why? Because research suggests that nighttime symptoms in particular leave
      patients more vulnerable to serious complications from the disease. Further, a
      recent survey suggests that the condition is having a greater impact on quality
      of life than many clinicians suspected. The new information has implications for
      how this very common condition should be best managed.

PMID- 11530660
TI  - [Laboratory photobioreactors].
AB  - Growing phototrophic microorganisms consume the light energy. These
      microorganisms most often suffer from light deficiency because of exponential
      decrease in the energy of light passing through an absorbing medium. Therefore,
      effective distribution of light within the cultures is needed for their intensive
      cultivation. This is possible in special devices called photobioreactors. The
      photobioreactors described in the literature are classified into several types
      according to their geometric features. Their advantages and drawbacks are
      analyzed. Criteria currently used for comparing various photobioreactors are
      specified.

PMID- 11530661
TI  - [Degradation of mineral oil by Acinetobacter calcoaceticus strain].
AB  - The Acinetobacter calcoaceticus strain TM-31 has been isolated from a microbial
      assemblage of a pilot plant purifying waste water polluted with mineral oil. This
      strain is capable of efficient degradation of components of mineral oil (alkanes,
      isoalkanes, and alkyl residues of the naphthene and arene fraction. The strain
      bears stably inherited plasmids of sizes 120, 9, and 8 kb, which can be
      transferred into plasmid-free cells of the parental strain and into bacteria of
      the genus Pseudomonas and ensure the degradation of hexadecane and mineral oil.

PMID- 11530662
TI  - [The treatment industrial sewage of nonferrous heavy metals using biosorbents].
AB  - Producers of the antibiotics neomycin and lincomycin were most potent in sorbing
      nonferrous metals; they removed 99% Zn and Cd and 95% Ni. The degree of metal
      sorption increased with an increase in solution pH and calcium content in the
      biomass. Dynamic studies of biosorbents prepared from microbial biomass showed
      that neomycin industrial waste products are highly efficient in treating galvanic
      washing water. The total dynamic exchange capacities by nickel and cadmium were
      6.85 and 7.16 mg/ml, respectively.

PMID- 11530663
TI  - [Study of the stability association of oil-degrading microorganisms in an open
      system].
AB  - Investigation of the stability of an association of active hydrocarbon-oxidizing
      microorganisms grown on diesel fuel showed that not all members of the
      association were competitive in an open flow system. The abundance of some
      strains considerably decreased during cultivation. One of the strain groups had
      consistently high cell titers, both in the medium and on a support. This prompts
      the authors to use these strains as degraders of diesel fuel.

PMID- 11530664
TI  - [Effects of exogenous factors on the activity of enzymes involved in carbon
      metabolism in thermoacidophilic bacteria of the genus Sulfobacillus].
AB  - Aerobic thermoacidophilic chemolithotrophic bacteria Sulfobacillus
      thermosulfidooxidans 1269T and Sulfobacillus thermosulfidooxidans subsp.
      asporogenes 41 were shown to be resistant to stress factors, including high
      concentrations of Zn2+ (0.8 M) and H+ (pH 1.2) that exceeded the optimum values.
      The growth and biomass gain rates decreased, but bacteria retained their
      functions. The activity of nearly all enzymes involved in carbon metabolism
      decreased. Glucose was primarily metabolized via the Entner--Doudoroff pathway.
      The activity tricarboxylic acid cycle enzymes decreased compared to that in cells
      grown under normal conditions. After saturation of the growth medium with 5 vol %
      CO2, sulfobacteria utilized glucose by the Embden-Meyerhof and pentose phosphate
      pathways under mixotrophic conditions.

PMID- 11530665
TI  - [Selection of a mixed culture of cellulosolytic thermophilic anaerobes from
      various natural sources].
AB  - Microbial associations capable of converting cellulose-containing substrates to
      ethanol and organic acids were isolated from natural sources. The resulting mixed
      cultures utilized cellulose, cellobiose, glucose, maize residue, cotton, and flax
      boon producing ethanol (up to 0.9 g/l) and acetic acid (up to 0.8 g/l). The most
      complete conversion of cellulose-containing substrates occurred at 60 degrees C,
      pH 7.0. The selected association of thermophilic anaerobic bacteria produced 0.64
      g ethanol per g substrate utilized at the ethanol/acetate ratio 4.7:1.

PMID- 11530666
TI  - [A two-stage technique for producing the microbial exopolysaccaride ethapolan
      with improved rheological properties].
AB  - A two-stage technique was proposed for cultivating producers of microbial
      exopolysaccharide ethapolan. The practical value of ethapolan is determined by
      its rheological properties. The use of a formaldehyde-supplemented medium at the
      second stage of cultivation improved the rheological properties of ethapolan
      without reducing its yield. This effect of formaldehyde was due to its binding to
      the exopolysaccharide, which altered the molecular-mass characteristics of the
      latter and protected the cells against the toxic action of formaldehyde. At all
      stages of its purification, ethapolan had improved rheological properties,
      suggesting that it was tightly bound to formaldehyde.

PMID- 11530668
TI  - [Immobilization of chloroperoxidase from Serratia marcescens].
AB  - A bacterial non-heme chloroperoxidase from Serratia marcescens W 250 was
      immobilized in calcium-alginate gel. Methods for stabilization of the immobilized
      enzyme were developed, and some kinetic parameters of the immobilized
      preparations were determined. The enzyme encapsulated into the gel granules in
      the presence of potassium ferricyanide followed by treatment with glutaraldehyde
      demonstrated the highest stability under the reaction conditions.

PMID- 11530667
TI  - [Optimization of conditions for transformation of maleic acid by immobilized
      cells of Alcaligenes xylosoxidans subspecies xylosoxidans 260].
AB  - Immobilized cells of Alcaligenes xylosoxidans subsp. xylosoxidans 260 used 98% of
      maleic acid (initial concentration of 5.0 g/l medium) in periodic conditions for
      48 h. Free cells transformed only 26% of substrate in 96 h. Immobilized cells of
      a selected S-variant of A. xylosoxidans used maleate (30.0 g/l) entirely in 96 h
      during periodic cultivation and only 15.0 g/l of maleate in continuous
      cultivation at a flow rate of 0.03 h-1.

PMID- 11530669
TI  - [Effect of cloned DNA fragment from Streptomyces chrysomallus No.2 on metabolism
      in Streptomyces strains].
AB  - The effects on cloned DNA fragment carrying an actinomycin resistance determinant
      on physiological processes in streptomyces strains with various potencies in
      producing this antibiotic, their inactive mutants, and model strain of
      Streptomyces lividans 66 were studied. This fragment was shown to modulate
      bacterial resistance to actinomycin and biosynthesis of antibiotics.

PMID- 11530670
TI  - [Galactomannan from ambiguous Crazyweed (Oxytropis ambigua (Pall) DC)].
AB  - A galactomannan with a molecular weight of 735 kDa was first isolated and
      purified from seeds of ambiguous crazyweed Oxytropis ambigua (Pall) DC. (family
      Leguminosae) with a yield of 3.6%. Its aqueous solutions displayed an optical
      activity ([alpha]D = 73.32 degrees) and high viscosity ([eta] = 644 ml g-1).
      Chemical analysis and 13C-NMR spectroscopy revealed the presence in the
      heteropolysaccharide of D-mannopyranose and D-glucopyranose at a molar ratio of
      1.39:1. The linear backbone of its macromolecule consists of 1.4-beta-D
      mannopyranose residues. Single beta-D-galactose residues substitute 72% of
      mannoses to form branches.

PMID- 11530671
TI  - [Phenolic compounds in medicinal plants].
AB  - Compositions of phenolic substances were studied in leaves of 21 species of
      medicinal plants. Flavonoid levels varied from 1.94 to 5.42%, whereas total
      amounts of monomeric polyphenols and hydroxybenzoic acids were estimated as 0.27
      to 0.57%, and hydroxycinnamic acids and their esters with quinic acid, 0.09 to
      0.18%. Condensed and polymerized polyphenols were detected in amounts of 0.41 to
      1.20%. Qualitative compositions of flavonoids in leaves of seven plants studied
      were presented. The developed analytical procedures may be useful for plant
      polyphenol studies and as the basis of hemotaxonomy.

PMID- 11530672
TI  - [Specific density of leaf as a characteristic of the photosynthetic apparatus].
AB  - At early stages of ontogeny (up to 50-60% of the maximum leaf area) of wheat
      (Triticum aestivum L.), meadow fescue (Festuca pratensis Huds.), reed fescue (F.
      arindinacea Schreb.), and sugar beet (Beta vulgaris L. var. saccharifera (Alef)
      Krass), there is correlation between changes in the specific leaf density (SLD),
      rate of photosynthetic CO2 assimilation; activity of the key photosynthetic
      enzyme ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco, EC 4.1.1.39);
      and concentration of chlorophyll (Chl) a, Chl b, carotenoids, and soluble leaf
      proteins. However, there is no correlation of SLD with the activity of
      phospho(enol)pyruvate carboxylase (EC 4.1.1.31). Senescence of leaves was
      accompanied by a decrease in the SLD value. Treatment with cytokininomimetics (6
      benzylaminopurine and Metribuzin) caused an increase in the SLD value. The
      specific leaf density is suggested to be a structural and functional
      characteristic of the photosynthetic apparatus of agricultural plants.

PMID- 11530673
TI  - [Gallic acid: a potent inhibitor of tetramethylbenzidine peroxidation in aqueous
      and micellar media].
AB  - Gallic acid competitively inhibited 3,3',5,5'-tetramethylbenzidine peroxidation
      both in 0.01 M phosphate buffer (pH 6.4) (KI 13.3 microM) and in reversed aerosol
      OT micelles of different hydration degrees dispersed in heptane (KI 21.3 to 29.3
      microM). The average number of free radical particles terminated by one inhibitor
      molecule (f) was estimated to be 1.3 to 1.6 in aqueous buffer solutions and 1.08
      to 2.72 in reversed micelles, depending on their hydration.

PMID- 11530674
TI  - [Changes in the composition of volatile compounds during processing and storage
      of Jerky sausages].
AB  - The change in the composition of volatile components during aging and storage of
      jerky sausages containing a mixture of Lactobacillus plantarum and Staphylococcus
      carnosus as fermenting cultures was studied by high-performance capillary gas
      chromatography and gas chromatography-mass spectrometry. A total of 52 compounds
      were identified. It was found that sausage storage is accompanied by a
      significant increase in the concentration of flavoring aldehydes. The terpene
      concentration monotonously increases with sausage aging and storage.

PMID- 11530675
TI  - [Biological deacidification of wines using lactic-acid bacteria and yeasts].
AB  - Based on a study of 200 lactic-acid bacteria monocultures and 30 associating
      lactic bacteria and yeasts cultures, a stable association was created formed by
      Leuconostoc oenos, Pediococcus pentosaceus and Saccharomyces cerevisiae yeasts,
      intended for the biological deacidification of wine. Physiology of microorganisms
      and their effect on the wine chemical composition was studied. By means of
      selective association, high quality fine wines were produced from the high-acid
      wines.

PMID- 11530677
TI  - Outbreak news. Cholera, India.

PMID- 11530676
TI  - [A new micromethod for differential quantitative assay of zeatin and zeatin
      riboside].
AB  - A new method is proposed for differential quantitative assay of two major
      endogenous cytokinin forms. It is based on determination of two effective
      parameters-concentrations of zeatin and zeatin riboside--with the use of
      appropriate antigens as standards. The method can be used for determining
      cytokinins in small samples of plant tissues without extract fractionation. This
      study pioneers in quantitation of changes in the hormonal status of ovules and
      ovaries of Triticum aestivum L. at early stages of embryogeny. A gradual increase
      in the content of the active and storage forms of the hormones from the ovary to
      the ovule was revealed.

PMID- 11530678
TI  - Global agenda on influenza.

PMID- 11530679
TI  - Prevention of mother-infant HIV transmission. Thailand, 1998-2000. Part I.

PMID- 11530680
TI  - [Neoral (Cyclosporin microemulsion preconcentrate): pharmacokinetics,
      pharmacodynamics and its improved clinical outcome].
AB  - Sandimmun displays considerable inter- and intra-patient variability because its
      absorption is bile-dependent and affected by concomitant intake of food. Neoral
      is a microemulsion preconcentrate; a microemulsion is a mixture of the lipophilic
      active substance with accurately balanced amounts of lipophilic solvent,
      hydrophilic solvent and surfactant. As the result of advanced microemulsion
      technique, Neoral has more consistent and improved absorption characteristics.
      Cyclosporin (cyclosporin A) has been used as an immunosuppressive agent. The
      major pharmacodynamic action of cyclosporin within T cells is calcineurin
      inhibition. The complex cyclophilin-cyclosporin competitively binds to the Ca(2+)
      and calmodulin-dependent phosphatase calcineurin which then inhibits downstream
      dephosphorylation and activation of NFAT(transcription factor). The greatest
      calcineurin inhibition is seen 1-2 h after administration of Neoral in parallel
      to the highest blood concentration. Variability in cyclosporin exposure was also
      identified as a risk factor for acute rejection in organ transplant recipients.
      "Absorption profiling" provides a more accurate prediction of drug exposure and
      leads to less acute rejection and toxicity. The evolution of Neoral monitoring
      strategies from trough level to absorption profile will raise the standard of
      performance of Neoral, resulting in clinical benefits for transplant patients.

PMID- 11530681
TI  - [A pharmacological profile of clobazam (Mystan), a new antiepileptic drug].
AB  - Clobazam (CLB) is a new antiepileptic drug that is the first 1,5-benzodiazepine
      (BZP) having nitrogen atoms in the 1 and 5 positions of the heterocyclic ring,
      whose chemical structure was designed to give it a different pharmacological
      profile from that of 1,4-BZPs. Although CLB has a Ki value of 2,130 nM and thus
      has a lower affinity for the BZP receptor than 1,4-BZPs, it had the selectivity
      to omega 2 receptor contributing to anticonvulsive actions compared with omega 1
      receptor in relation to other CNS activities such as sedation. CLB had a wide
      spectrum of anticonvulsive actions against seizures in several animal models
      induced by chemical convulsants and maximal electroshock. CLB reduced both
      seizure stage and afterdischarge duration in a dose-dependent manner in amygdala
      or hippocampal kindled rats. Usefulness of an anticonvulsant is generally
      assessed by quoting the protective index (PI) in the ratio of TD50 to ED50. As
      the PI for CLB was greater than that for 1,4-BZPs, it suggested that CLB was
      superior to 1,4-BZPs in tolerability while showing anticonvulsive actions. In
      clinical studies, CLB was used as an adjunctive treatment in patients with
      refractory epilepsies. From both experimental and clinical observations, CLB was
      proven to possess a wide spectrum of activity, high effectiveness and good
      tolerability in several types of epilepsies.

PMID- 11530682
TI  - [The new experimental ulcerative colitis model in rats induced by subserosal
      injection of acetic acid].
AB  - We have developed a new experimental ulcerative colitis model in rats. Topical
      pathological change of a round or a ellips shape was induced by subserosal
      injection of acetic acid (20%, 0.02 ml) into the middle colon of rats. The size
      of the induced ulcer could directly be measured using a caliper gauge, and the
      result was expressed as the ulcer area (mm2). We determined the concentration of
      leukotriene B4 (LTB4), which is one of important clinical factors, in the ulcer
      region and found that the quantity of LTB4 was well correlated with the size of
      the ulcer area. Histopathological studies of the ulcer region demonstrated that
      there were some morphological similarities to the human form of ulcerative
      colitis, characterized by edema, necrosis, inflammatory cell infiltration, crypt
      abscess and granulation tissue formation. Effects of 5-aminosalicylic acid and
      sodium prednisolone phosphate were investigated by intrarectal administration in
      this colitis model. The predominant improvement of colitis was obtained from both
      treatments in the ranges of the clinical doses of each drug. In conclusion, we
      suggest that this colitis model provides a new way for quantitative evaluation of
      the efficacy of new therapeutic agents for ulcerative colitis.

PMID- 11530683
TI  - [Assay in high throughput screening].
AB  - HTS (High Throughput Screening) has been put into practice in recent years. HTS
      is aiming to discover lead compounds for medicinal drugs. High efficiency must be
      achieved in all the processes including sample preparation, assay procedure,
      automation and data management. This review will focus on the aspects concerned
      with the assay technology and the efficiency in HTS. One of the major trends in
      HTS is assay miniaturization using high-density microplates with 384 and 1536
      wells. This allows us to increase the throughput and to decrease the cost. The so
      called "mix and measure" or "homogeneous" assay system, which has no separation
      steps such as washing or filtration, is effective for this purpose. The
      homogeneous assays, such as scintillation proximity assay (SPA), fluorescence
      energy transfer (HTRF, LANCE) and fluorescence polarization (FP), are frequently
      used. The reporter gene assay or the cell proliferation assay can be adapted for
      the homogeneous assay using high-density plates. In addition, HTS measuring the
      intracellular Ca2+ influx is also possible using a CCD Imager. The assay quality
      as well as the efficiency is also important especially in HTS. The Z'-factor
      provides a good tool for evaluating the quality of assays.

PMID- 11530684
TI  - [Animal models and peripheral nociception tests for the study of neuropathic
      pain].
AB  - Neuropathic pain associated with abnormal tactile and thermal responses that are
      extraterritorial to the injured nerve is known to be difficult to diagnose and
      treat because of clinical observation of limited responsiveness to opioids and
      non-steroidal anti-inflammatory drugs. To reproduce the different pathological
      changes observed in neuropathic pain patients, several laboratory animal models
      have been proposed. Recent studies using such models suggest the involvement of
      neuronal plasticity in pain pathways through nociceptive neurons. Our new
      experimental model using specific pain-producing molecules that clearly
      distinguish three different nociceptive fibers from each other reproduces
      neuropathic pain-like hyperalgesia and less sensitivity to morphine. After nerve
      injury, the nociceptive responses through type I neurons, which are polymodal C
      fibers and drive NK1-receptor mechanisms in spinal pain transmission, were
      completely lost, but without changes in type II ones, which are polymodal C
      fibers and drive NMDA receptor-mechanisms, while type III ones, which are
      capsaicin-insensitive (possibly A-fibers) and drive NMDA-receptor mechanisms,
      were markedly enhanced. Such pain transmission switch mechanisms are clearly
      consistent with clinical effectiveness including less sensitivity to morphine and
      more sensitivity to NMDA-antagonists. This article also presents currently used
      methods for experimental neuropathic pain models.

PMID- 11530685
TI  - [Torasemide (LUPRAC): a review of its pharmacological and clinical profile].
AB  - Loop diuretics potently excrete water and electrolytes and therefore have been
      widely prescribed for the treatment of various kinds of edema for a long time.
      The potent diuretic action of loop diuretics, however, often causes hypokalemia,
      and therefore potassium sparing diuretics have also been supplied as a
      concomitant drug. Torasemide (LUPRAC), a novel diuretics, shows not only an
      effective loop diuretic action but also a potassium sparing action due to its
      anti-aldosteronergic effect. Torasemide also has a high bioavailability and is
      only slightly influenced by meals in humans. In addition, its pharmacodynamic
      features contribute to its stable diuretic action without any individual
      differences. In animal experiments, torasemide showed about a tenfold more potent
      diuretic action in comparison with furosemide, an authentic loop diuretic. On the
      one hand, the increase in the urinary potassium excretion by torasemide was
      relatively slight compared to the increase in urinary sodium excretion and, as a
      result, the urinary sodium to potassium (Na+/K+) ratio increased. The diuretic
      profile of torasemide was equal to that of the concomitant use of furosemide and
      an anti-aldosteronergic drug, spironolactone. Torasemide showed a significant
      efficacy and safety in comparison with furosemide in the patients with edema in
      both domestic and foreign clinical studies. Moreover, torasemide also showed a
      decreased rate of cardiac death in comparison to furosemide in patients with
      chronic heart failure in a large-scale clinical study (TORIC Study). The
      difference in cardiac death between these two diuretics has been suggested to
      depend on the anti-aldosteronergic effect of torasemide. In Japan, no new loop
      diuretics have been developed in over 10 years. Torasemide is therefore expected
      to be useful as an effective diuretic for diseases with edema.

PMID- 11530686
TI  - Gene structures and catalytic mechanisms of microbial enzymes able to biodegrade
      the synthetic solid polymers nylon and polyester polyurethane.

PMID- 11530687
TI  - 5-Aminolevulinic acid: production by fermentation, and agricultural and
      biomedical applications.

PMID- 11530688
TI  - Biotransformations of explosives.

PMID- 11530689
TI  - Tumour-selective Salmonella-based cancer therapy.

PMID- 11530690
TI  - Bioconjugation for enzyme technology.

PMID- 11530691
TI  - Regulation of muscle glycogen phosphorylase by physiological effectors.

PMID- 11530692
TI  - Kinetic analysis for analyte-receptor binding and dissociation in biosensor
      applications: a fractal analysis.

PMID- 11530693
TI  - Pyrolysis in biotechnology.

PMID- 11530694
TI  - Industrial purification of pharmaceutical antibodies: development, operation, and
      validation of chromatography processes.

PMID- 11530695
TI  - Biotechnological approaches to fight pathogens at mucosal sites.

PMID- 11530696
TI  - Genetic improvement of iron content and stress adaptation in plants using
      ferritin gene.

PMID- 11530697
TI  - Cyanobacterial exopolysaccharides: their nature and potential biotechnological
      applications.

PMID- 11530698
TI  - Applications, and efficient large-scale production, of recombinant human
      epidermal growth factor.

PMID- 11530699
TI  - Use of the baculovirus expression system for the generation of virus-like
      particles.

PMID- 11530700
TI  - Expression of insulin in yeast: the importance of molecular adaptation for
      secretion and conversion.

PMID- 11530701
TI  - [Differential diagnosis and treatment of girls with 46XY-karyotype and androgen
      insensitivity syndrome].
AB  - The importance of the secretion and action of androgens during the critical
      period of male sexual development is exemplified in patients with androgen
      insensitivity syndrome. Their karyotype is always 46XY. In 2 sisters, aged 11 and
      13 years, the androgen insensitivity syndrome was diagnosed based on an androgen
      receptor gene mutation. Ambiguous genital development of a new-born was shown to
      be due to a lack of testosterone production, based on a luteinizing hormone
      receptor gene mutation. Finally, in a phenotypically female new-born a gene
      mutation of 17-beta hydroxysteroid dehydrogenase type 3 was found to be
      responsible for insufficient testosterone synthesis during embryonic development.
      The presentation of a patient, and specifically a neonate, with abnormal genital
      development represents a difficult diagnostic and therapeutic challenge. Referral
      to a centre with experience in the diagnosis and management of disorders of
      sexual development is advised where the emphasis should be on psychological and
      genetic counselling.

PMID- 11530702
TI  - [Angiogenesis and arteriogenesis; the long road from concept to clinical
      application].
AB  - In patients with obstructive artery disease, two different forms of compensatory
      vessel growth occur; angiogenesis and arteriogenesis. Angiogenesis is the
      formation of a capillary network, through the activation and proliferation of
      endothelial cells in ischaemic tissue. Arteriogenesis is the transformation of
      pre-existent collateral arterioles into functional collateral arteries.
      Circulating blood cells, especially monocytes, play an important role in the
      arteriogenesis process. Animal experiments have demonstrated that local treatment
      with monocyte chemoattractant protein-1 results in an elevated accumulation of
      monocytes/macrophages and an increased growth of collateral vessels. The
      stimulation of arteriogenesis will probably result in a greater increase in blood
      flow to the ischaemic tissue, than the stimulation of angiogenesis. This can be
      explained by the difference in diameter between the collateral vessels formed in
      arteriogenesis and the capillaries formed in angiogenesis. Research to the
      efficacy of growth factors that stimulate the arteriogenesis process is still at
      an experimental stage. The stimulation of arteriogenesis is studied in models of
      both peripheral and coronary obstructive disease.

PMID- 11530703
TI  - [Consequences of diethylstilbestrol during pregnancy; 50 years later still a
      significant problem].
AB  - Since the 1940s, diethylstilbestrol (DES) has been administered to about three
      million pregnant women in the United States and in the Netherlands, between 1947
      and 1975, to about 220,000. The most important consequences described are: for
      DES mothers an increased risk of mammary carcinomas and for DES daughters a 1 in
      1000 chance of clear cell adenocarcinoma (CCAC) as well as an increased risk of
      (pre)malignant abnormalities of the stratified epithelium in the vagina and
      cervix. In addition to this, DES daughters frequently have developmental
      disorders of the cervix and corpus uteri. In connection with this fertilisation
      disorders have been described as well as unfavourable outcomes of pregnancy: more
      ectopic pregnancies, abortion and premature birth. DES sons exhibit an increased
      frequency of several benign abnormalities of the genitalia. The DES problem
      continues to be an important issue. The entire cohort of DES mothers is in the
      age group with a high risk of mammary carcinoma. The youngest DES daughters will
      be of childbearing age for at least another 15 years; the risk of ectopic
      pregnancies and pre-term labour is increased. The oldest DES daughters are now
      reaching postmenopausal age. The incidence of CCAC of the vagina and cervix in
      the population is bimodal, with a second peak at older age. It is still unknown
      if at this age DES daughters will have an increased incidence of these
      malignancies. From animal experiments it becomes clear that DES administration to
      pregnant mice results in an increased incidence of genital tumours not only in
      the second generation but also in the third. This has yet to be investigated in
      humans and deserves special attention. The legally imposed destruction of patient
      files after a period of ten years is a serious threat to patient care and
      scientific investigation, notably in obstetrics and child medicine.

PMID- 11530704
TI  - [Physician's role in posthumous donation].
AB  - According to the Dutch Organ Donation Act, the explicit consent of either the
      donor or the relatives of the deceased is required for organ retrieval to be
      legitimate. Every Dutch citizen aged 12 years or over can record, in the national
      donor register, their consent to donation, their objection to donation or their
      wish to leave the decision to their relatives. The doctor, who establishes the
      death of a possible donor, is obliged to consult the national donor register. If
      doctors do not consult the register because the relatives object to donation,
      then they have failed to meet their obligations under the Organ Donation Act.
      Such an action disregards the donor's right to self-determination and the
      legitimate interests of those waiting for a suitable donor organ. It is
      acknowledged that some aspects of the Act are unclear, which may in part explain
      the reluctant attitude of doctors towards donation. These aspects include the
      procedures for donation by incompetent patients, the question as to when measures
      required to preserve organ function can be started, and the physician's duty of
      confidentiality.

PMID- 11530705
TI  - [Diagnostic image (32). Gout tophus].
AB  - A 65-year old man had gout and a secondary infection of a tophus with Pseudomonas
      at the metatarsophalangeal joint of the right first toe.

PMID- 11530706
TI  - [From gene to disease; from defective chloride ion transport to cystic fibrosis].
AB  - Cystic fibrosis is an autosomal recessive disorder affecting the lungs, pancreas,
      intestines, sweat ducts and liver, due to an abnormal salt transport across the
      apical border of epithelial cells. Mutations in the CF underlying gene, the
      cystic fibrosis transmembrane conductance regulator (CFTR) gene, result in most
      cell types in an misprocessing so that little of the protein reaches the
      membranes. In case of clinical suspicion and/or doubtful sweat test results,
      mutation analysis can support the diagnosis of CF. Also carrier detection is
      offered.

PMID- 11530707
TI  - [High sensitivity of Escherichia coli to antimicrobial agents used for first-line
      treatment of urinary tract infections; results of an examination of feces of
      healthy subjects in Friesland].
AB  - OBJECTIVE: To determine the basic sensitivity of Escherichia coli in the province
      of Friesland, the Netherlands, to antimicrobial agents used by general
      practitioners to treat urinary tract infections. DESIGN: Inventory. METHOD: Fifty
      general practitioners in the province were asked in 1999 to have faeces submitted
      by patients who had not been using antibiotics for at least one month. E. coli
      was isolated from the faeces using an elective medium. The proportions of
      resistance were compared with those of strains isolated in urine sent for
      examination to Friesland Public Health Laboratory by a clinic, outpatient
      department, general practice or nursing home. RESULTS: The sensitivities were
      tested of 240 strains from 240 healthy subjects (73 males and 167 females; mean
      age 47 years (range 0-84)). The proportions of strains resistant to the agents
      tested were as follows: nitrofurantoin: 0.8%, trimethoprim: 10%, co-trimoxazole:
      10%, amoxicillin: 15%, amoxicillin-clavulanic acid 0.4%. Forty-eight per cent of
      the strains showed intermediate susceptibility to amoxicillin, 63% to
      amoxicillin/clavulanic acid. The resistance was lower than in isolates submitted
      for examination from general and specialist practices. CONCLUSION: The
      antimicrobial agents mentioned are still useful for treatment of urinary tract
      infections in the general practice.

PMID- 11530708
TI  - [Diagnostics in clinically occult, radiologically suspect breast lesions more
      often surgery than needle diagnostics with image monitoring].
AB  - OBJECTIVE: To inventory the diagnostic methods used in patients with clinically
      occult, radiologically suspect breast lesions. DESIGN: Enquiry. METHOD: The
      departments of radiology of all Dutch hospitals were sent a list in January 2000
      containing questions concerning the number of thread localizations in 1999 and
      the use of cytological or histological needle diagnostics with image monitoring
      prior to surgical intervention in clinically occult, radiologically suspect
      breast lesions. Of the 120 questionnaires mailed, 74 (62%) were completed and
      returned by clinics throughout the country. RESULTS: Fifty-one of the 74
      hospitals (69%) had prior to operation carried out histological or cytological
      examinations and in these 51 hospitals this was done in 1743 of the 2857 lesions
      (61%): fine-needle aspiration cytology was performed in 1046 (/1743 = 60%; /4140
      lesions in all 74 hospitals = 25%) and/or histological needle biopsy in 784 (45%;
      /4140 = 19%). CONCLUSION: In less than half of all non-palpable breast
      abnormalities non-surgical methods of diagnosis are used, histological needle
      biopsy less often than fine needle aspiration cytology.

PMID- 11530709
TI  - [Kidney insufficiency and persistent hypotension following compromise of the
      renin-angiotensin system in a fetus and a young infant].
AB  - A newborn girl had chronic renal failure following prenatal exposure to an
      angiotensin-converting enzyme (ACE) inhibitor, and a young infant with congenital
      nephrotic syndrome, showed persistent hypotension with neurological complications
      following bilateral nephrectomy at the age of 4 months. Both died. The renin
      angiotensin system (RAS) is well-known for its regulatory function with respect
      to blood pressure, renal haemodynamics, fluid balance and electrolyte balance.
      Furthermore, its role in growth and differentiation of the kidneys and urinary
      tracts is becoming clearer. The RAS is highly important for the foetus and young
      infant. Extreme caution should be exercised with prenatal exposure to ACE
      inhibitors or angiotensin receptor blockers and bilateral nephrectomy in young
      infants.

PMID- 11530710
TI  - [Bizarre advertisements by hospitals in the Dutch Journal of Medicine].

PMID- 11530711
TI  - [From gene to disease; from polycystines to polycystic kidney disease].

PMID- 11530712
TI  - Respiratory psychophysiology and behavior modification.
AB  - This article was written as an introduction to a special issue of Behavior
      Modification dedicated to studies in the field of respiratory psychophysiology.
      Although the invited articles that constitute this special issue cover a fairly
      broad range of topics, priority was given to articles that focus on the role of
      respiration in panic disorder. Attention is directed to the fundamental role of
      breathing in applied psychophysiology and to the encouragement of research in the
      modification of breathing behavior. The connection between respiratory
      psychophysiology and behavior modification is explained by reference to (a) a
      recent article on Pavlovian and operant control of breathing behavior and (b)
      four published volumes of selected articles dedicated exclusively to the field of
      respiratory psychophysiology. The present special issue of Behavior Modification
      marks the fifth volume.

PMID- 11530713
TI  - Learning in respiratory control.
AB  - In this article, it is argued that learning participates to fulfill the metabolic
      requirements by adapting respiratory control to changing internal and external
      states. Recent classical-conditioning experiments in newborn mice or adult rats
      show the close link between conditioned respiratory and arousal responses. The
      conditioned fear model may be a suitable and largely unexplored model of
      emotionally induced hyperventilation. The parabrachial nucleus and periacqueducal
      grey may play a pivotal role in the ventilatory component of conditioned fear.
      The sensitivity of breathing to conditioning in newborn and adult animals
      suggests that learning processes may shape breathing pattern throughout life.

PMID- 11530714
TI  - Respiratory dysregulation in anxiety, functional cardiac, and pain disorders.
      Assessment, phenomenology, and treatment.
AB  - Respiration is a complex physiological system affecting a variety of physical
      processes that can act as a critical link between mind and body. This review
      discusses the evidence for dysregulated breathing playing a role in three
      clinical syndromes: panic disorder, functional cardiac disorder, and chronic
      pain. Recent technological advances allowing the ambulatory assessment of
      endtidal partial pressure of CO2 (PCO2) and respiratory patterns have opened up
      new avenues for investigation and treatment of these disorders. The latest
      evidence from laboratories indicates that subtle disturbances of breathing, such
      as tidal volume instability and sighing, contribute to the chronic hypocapnia
      often found in panic patients. Hypocapnia is also common in functional cardiac
      and chronic pain disorders, and studies indicate that it mediates some of their
      symptomatology. Consistent with the role of respiratory dysregulation in these
      disorders, initial evidence indicates efficacy of respiration-focused treatment.

PMID- 11530715
TI  - Dyspnea during panic attacks. An Internet survey of incidences of changes in
      breathing.
AB  - This article presents the results of a survey that investigated breathing-related
      symptoms of panic attacks together with the frequency of other symptoms reported
      by active panickers. All the participants of this study experienced naturally
      occurring panic attacks and sought treatment guidance by visiting a Web site
      devoted to the treatment of panic. The results of a symptom questionnaire showed
      that 195 respondents (95.1%) reported breathing changes during panic attacks, and
      remarkable dyspnea was reported by more than two thirds (68%) of respondents.
      These findings are consistent with earlier studies but are contrary to
      conclusions that only a small number of panickers report shortness of breath as a
      symptom. This study concludes that outside of the laboratory, a large majority of
      people who suffer from panic attacks experience symptoms of dyspnea.

PMID- 11530716
TI  - Respiratory and cognitive subtypes of panic. Preliminary validation of Ley's
      model.
AB  - A review of the panic disorder literature strongly suggests subtypes of panic
      attacks, including a respiratory subtype. This study empirically tested several
      aspects of Ley's panic subtype theory, measuring end-tidal carbon dioxide (ETCO2)
      levels at baseline, during psychologic and respiratory stressors, and at
      recovery. As predicted, Type 1 (classic or respiratory) panickers had
      significantly lower resting ETCO2 compared to Type 3 (cognitive) and to controls.
      Type 3 panickers did not differ from controls. Physiologic findings support the
      existence of respiratory and other subtypes of panic attacks in panic disorder.
      More complex measures of respiration and other physiology are likely required to
      elicit full subtype profiles. Distinguishing between chronic (compensated)
      hyperventilators and acute hyperventilators will likely be useful in clarifying
      the subtypes. Recognizing the need for differential diagnosis of panic attacks
      can facilitate developing more specific treatment plans and interventions (e.g.,
      restoration of normal ETCO2 in Type 1), improving treatment success rates.

PMID- 11530717
TI  - Respiratory biofeedback-assisted therapy in panic disorder.
AB  - The authors describe a new methodologically improved behavioral treatment for
      panic patients using respiratory biofeedback from a handheld capnometry device.
      The treatment rationale is based on the assumption that sustained hypocapnia
      resulting from hyperventilation is a key mechanism in the production and
      maintenance of panic. The brief 4-week biofeedback therapy is aimed at
      voluntarily increasing self-monitored end-tidal partial pressure of carbon
      dioxide (PCO2) and reducing respiratory rate and instability through breathing
      exercises in patients' environment. Preliminary results from 4 patients indicate
      that the therapy was successful in reducing panic symptoms and other
      psychological characteristics associated with panic disorder. Physiological data
      obtained from home training, 24-hour ambulatory monitoring pretherapy and
      posttherapy, and laboratory assessment at follow-up indicate that patients
      started out with low resting PCO2 levels, increased those levels during therapy,
      and maintained those levels at posttherapy and/or follow-up. Partial dissociation
      between PCO2 and respiratory rate questions whether respiratory rate should be
      the main focus of breathing training in panic disorder.

PMID- 11530718
TI  - Respiratory psychophysiology in hypertension research.
AB  - The pathogenesis of hypertension results from an interaction of genetic and
      environmental factors. Behavioral factors might participate in sodium sensitive
      forms of hypertension via a cascade of physiological responses triggered by
      conditioned inhibition of breathing. When an individual decreases ventilation
      sufficient to increase pCO2 but not sufficient to activate chemoreceptor
      reflexes, plasma pH decreases transiently to stimulate a renal mechanism that can
      expand plasma volume via sodium retention. The combination of high resting pCO2
      and high sodium intake elevates resting blood pressure in laboratory animals and
      healthy human participants. In the natural environment, this mechanism seems to
      be more important for the development of hypertension in women than in men,
      perhaps due to differential expression of anger and aggression. Studies are
      needed to clarify the role of breathing pattern in individual differences in
      resting pCO2 and the effects of breathing interventions on salt sensitivity and
      sodium sensitive forms of hypertension.

PMID- 11530720
TI  - Relaxation therapy in adult asthma. Is there new evidence for its effectiveness?
AB  - Studies of relaxation training for adult asthma patients were reviewed for the
      period between 1980 and 2000. Six controlled and three uncontrolled studies were
      identified, employing a variety of methods, such as progressive relaxation,
      functional relaxation, autogenic training, or yoga. Most studies had low sample
      sizes and suffered from one or more methodological deficiencies, such as
      suboptimal data analysis, high dropout rates, problematic measurement procedures,
      or insufficient descriptions of methodology and results. Overall effects on
      parameters of lung function, symptoms, medication consumption, and health care
      use were generally negligible. Problems with the underlying rationale of
      relaxation therapy in asthma are discussed from a psychophysiological viewpoint.
      Examples are given of potential beneficial and detrimental effects of these
      techniques on lung function with respect to emotional processes, the
      musculoskeletal system, and ventilation as targets of a relaxation intervention.
      It remains to be demonstrated that relaxation training can significantly
      contribute to the standard treatment of asthma in adult patients.

PMID- 11530719
TI  - Critical conditions for hyperventilation responses. The role of autonomic
      response propositions during emotional imagery.
AB  - Hyperventilation is often conceived of as part of a fight-or-flight response,
      triggered by situations with high arousal and negative valence. However, a
      previous study using emotional imagery found hyperventilation responses during
      imagery of high-arousal scenes regardless of their valence. Those imagery scripts
      contained suggestions of autonomic activity, which may have partly induced or
      enhanced the hyperventilatory responsivity. The present study used four emotional
      scripts--depicting relaxing, fearful, depressive, and pleasant situations-
      without suggestions of autonomic or respiratory responses. After each imagery
      trial, participants rated their imagery for valence, arousal, and vividness.
      Fractional end-tidal carbon dioxide (FetCO2), inspiratory and expiratory time,
      tidal volume, and pulse rate were measured in a non-intrusive way. Results showed
      significant FetCO2 drops during the fearful and pleasant scripts. However, this
      effect was much smaller compared to imagery scripts with autonomic response
      propositions. Participants imagining scripts without autonomic response
      information found it harder to imagine the scripts vividly and reported lower
      levels of subjective arousal.

PMID- 11530721
TI  - [Postprandial natriuresis].
AB  - Of the common responses elicited by differences in the composition of the meal,
      specific effects on renal fluid-electrolyte excretion that manifest themselves as
      postprandial natriuresis have attracted significant interest. Unfortunately, our
      understanding of their mechanisms remains incomplete. Hepatorenal reflexes,
      dopamin action, urodilatin secretion and NO synthesis have been the candidates
      most frequently cited to contribute to postprandial natriuresis. The recent
      identification of a novel class of natriuretic peptides named guanylins has
      brought a new impact on water-sodium homeostasis regulation studies. The
      elucidation of mechanisms of postprandial natriuresis can be of importance in the
      research of primary hypertension. The article briefly reviews work in this area.

PMID- 11530722
TI  - [Precision-cut tissue sections--an important system for study of metabolism in
      vitro].
AB  - Tissue slices represent a useful in vitro method for metabolic, pharmacologic and
      toxicologic studies. To their major advantage belong preserved cell to cell
      interactions, architecture and complexity of the tissue. They enable to reduce
      the number of laboratory animals, that are necessary for research purposes.
      Tissue slices are more similar to in vivo situation than other in vitro models
      such as microsomes, cell suspensions or cell cultures. Slices can be cultured up
      to 72 hours or even more. Preparation of the slices is rapid and easy. Slices can
      be prepared from any organ. There is a possibility of cross-species comparison,
      co-culturing of slices derived from different organs. Excess of the material can
      be cryopreserved for later studies.

PMID- 11530723
TI  - [An overview of the regulation of basic functions of the digestive system].
AB  - The gastrointestinal system is the gate through which nutritive substances,
      vitamins, minerals, and fluids enter the body. Proteins, fats and complex
      carbohydrates are broken down into absorbable units (products of the digestion)
      in the digestive tract and finally they are absorbed together with vitamins,
      minerals and water into the blood or the lymph. The digestive and absorptive
      functions of the gastrointestinal tract depend on the various mechanisms, which
      adjust the food, put it through the gastrointestinal tract and mix it together
      with digestive enzymes secreted by the salivary glands, stomach, pancreas, small
      intestine and with bile. Some of these mechanisms depend on the spontaneous
      activity of the smooth muscles, others involve the somatic and autonomous
      reflexes, paracrine effects of the chemical substances, hormones and local
      gastrointestinal hormones. The aim of this paper is to review the essential
      factors participating in the regulation of these processes (mainly motility and
      secretion) from the mouth cavity, stomach, duodenum, gallbladder, pancreas, small
      intestine and large intestine to the defecation. The basic regulatory factors are
      summarized in the schemes from the sources of the physiological textbooks, which
      are accepted in the whole world for the education of physiology in the medical
      faculties.

PMID- 11530725
TI  - [QT interval dispersion].
AB  - Dispersion of QT intervals has been proposed as a measure of repolarization
      process inhomogeneity (and thus refractority inhomogeneity) of ventricular
      myocardium. Recently other possible explanation of this phenomenon has been
      intensively discussed. According to this concept QT dispersion is explained by
      different projections of the heart repolarization vector. Moreover, the
      reproducibility of the measurement of QT dispersion is rather low as it could be
      influenced both by intrinsic (e.g., amplitude of the T wave or U wave) and
      extrinsic (e.g. noise, amplitude and time parameters of recording) factors. Only
      markedly prolonged QT dispersion must be therefore interpreted as a sign of the
      abnormal course of the repolarization. Nevertheless, according to all mentioned
      facts the only serious interpretation of increased QT dispersion is that it
      reflects unspecific repolarization changes. More precious explanation is by then
      not possible (and it is disputable if it ever will be).

PMID- 11530724
TI  - [Procalcitonin--a marker of systemic infection and multiorgan dysfunction:
      characteristics of the gene and protein].
AB  - Procalcitonin (PCT) is a protein consisting of 116 aminoacids with molecular
      weight 13 kDa. It is encoded by CALC-1 gene. According to the basic and clinical
      research results PCT appears to be a highly sensitive and specific marker
      reflecting severity of the systemic inflammatory response to infectious stimuli.
      Despite the investigation focused on CALC-1 gene, little is known about the
      biology of PCT and cellular sources of PCT during inflammation. One of the
      possible sources may be human peripheral blood mononuclear cells. PCT is an
      indicator of bacterial infections minimally stimulated by viral infections,
      autoimmune diseases and tumors.

PMID- 11530727
TI  - [Effect of magnetic fields on embryonic mortality].
AB  - The effects of magnetic field of the intensity 0.07 T on embryonic mortality of
      chicken were studied. Embryonic mortality in eggs exposed to the magnetic field
      during their incubation was higher (14.28 +/- 3.14%; 18.57 +/- 4.03% resp. 18.95
      +/- 3.77%). In comparison with the control group (1.57 +/- 0.97%) all results
      were significantly different (p < 0.001). The negative effect of the magnetic
      field manifested also by the lower weight of the hatched chickens (33.58 +/- 2.07
      g; 33.09 +/- 3.73 g resp. 31.17 +/- 4.21 g) when compared with the control group
      (40.80 +/- 5.12 g) (p < 0.05).

PMID- 11530728
TI  - The Hippocratic concept of positive health in the 5th century BC and in the new
      millennium.

PMID- 11530726
TI  - [Role of orthogonal electrocardiography and vectorcardiography in a paradigm
      shift in diagnosis of left ventricular hypertrophy].
AB  - A new contingency approach to the ECG diagnostics of left ventricular
      hypertrophy, its theoretical background, and first results of experimental and
      clinical studies are presented. This approach considers false negative ECG
      results as a consequence of the relative voltage deficit and introduces a new
      parameter: the specific potential of myocardium. As well it considers nonlinear
      changes of non-spatial determinants with respect to the stage and progression of
      left ventricular hypertrophy. The potential advantages of the concept of the
      specific potential of myocardium can be summarized as follows: (1) It utilizes
      equally both electrocardiographic and echocardiographic information, without
      stressing the priority or neglecting any of particular methods and creates a
      broader basis for the clinical diagnosis of left ventricular hypertrophy, (2) It
      utilizes also the false negative ECG results for diagnostics and quantifies the
      relative voltage deficit.

PMID- 11530729
TI  - Aerobic exercise, gene expression and chronic diseases.

PMID- 11530730
TI  - Genetic variation and the response to exercise.

PMID- 11530731
TI  - Dietary and genetic effects on LDL heterogeneity.

PMID- 11530732
TI  - Essential fatty acids in somatic growth and brain development.

PMID- 11530733
TI  - Omega-3 fatty acids and cardiovascular disease.

PMID- 11530734
TI  - Omega-3 fatty acids in major depression.

PMID- 11530735
TI  - Nutrients and gene expression.

PMID- 11530736
TI  - Genetic variation and dietary response.

PMID- 11530737
TI  - Effect of genetic variation on the postprandial response. Results from the
      European Atherosclerosis Research Study II.

PMID- 11530738
TI  - Predisposing genes, high-risk environments and coronary artery disease: LPL and
      fibrinogen as examples.

PMID- 11530739
TI  - Role of genetic variation in establishing nutritional requirements: folate, a
      case in point.

PMID- 11530740
TI  - Genetic influences on serum LDL levels and on type I diabetes incidence in
      Sardinia.

PMID- 11530741
TI  - Osteoporosis, vitamin D receptor gene polymorphisms and response to diet.

PMID- 11530742
TI  - Interactions between the genome and the environment, with special reference to
      nutrient variation. New concepts, emerging methodologies and challenges.

PMID- 11530743
TI  - Declaration of Olympia on Nutrition and Fitness. Ancient Olympia, Greece, May 28
      29, 1996.

PMID- 11530744
TI  - [Intraoperative awareness and memory: it doesn't just happen to somebody else].

PMID- 11530745
TI  - [Neurosurgical air embolism. Transesophageal echocardiography and dogmatic
      positions].

PMID- 11530746
TI  - [Intraoperative memory. A study of its incidence in general anesthesia in 326
      patients].
AB  - OBJECTIVES: Measuring the incidence of intraoperative recall in our hospital.
      STUDY DESIGN: Prospective study. PATIENTS AND METHODS: Three hundred and twenty
      six patients who underwent a general anaesthesia for elective surgery on selected
      sites (general, urology, ORL, gynaecology and obstetrical, vascular and cardiac,
      thoracic) were interviewed on the first or the second postoperative day using a
      standard questionnaire. When recall was suspected, the anaesthetist was consulted
      and the anaesthetic record was looked at in order to evaluate the authenticity of
      any recollections. RESULTS: Four patients mentioned an anomaly evoking intra
      operative recall. The reduction in the anaesthetic level would explain authentic
      recollection for one patient. The recollection of another patient could not be
      truly verified. The site was the same for these two cases and the anaesthetic
      protocol for digestive surgery comprised curare and droperidol. The recollections
      for the two other patients did not correspond to the intraoperative period. The
      incidence of this phenomenon on the totality of sites was 0.6 per cent.
      CONCLUSION: This result conforms to other studies. This phenomenon is a quality
      indicator, but probably under estimated. Although retrospective, this evaluation
      is quick and easy. This research in post-operative period should be systematic in
      order to find the reason and to propose an early course of action for these
      patients. An analysis of the anaesthetic protocol is necessary when the frequency
      of intraoperative recall is too high.

PMID- 11530747
TI  - [Evaluation of antibacterial filters for peridural obstetrical anesthesia].
AB  - OBJECTIVES: To assess the antibacterial efficiency of filters used in obstetrics
      when epidural top-ups are performed. STUDY DESIGN: Observational prospective
      study. PATIENTS AND METHODS: We aseptically collected 201 antibacterial filters
      that had been used for top-ups with ropivacaine +/- sufentanil for epidural
      analgesia during labour. We flushed them first with 2 mL of saline and then with
      2 mL of a solution containing 1.5 x 10(6) Staphylococcus epidermidis/mL. The
      filtrates were incubated at 37 degrees C for 72 h. Number of top-ups and duration
      of epidural analgesia are expressed as median (extremes). RESULTS: 3 (1-10) top
      ups were performed for labour analgesia over a period of 6.5 h (1.8-18). After
      filtering, all the solutions were found to be sterile. Especially, when using
      Staphylococcus epidermidis solutions, bacteria were not found beyond any filter.
      These results suggest the integrity of the filter membrane after several boluses.
      No infection related to epidural analgesia was reported. CONCLUSION:
      Antibacterial filters provide a good protection against a potentially
      contaminated procedure during epidural top-ups.

PMID- 11530748
TI  - [Clonidine combined with flunitrazepam before carotid endarterectomy decreases
      cerebrovascular CO2 reactivity].
AB  - OBJECTIVE: Assess cerebrovascular CO2 reactivity changes using transcranial
      Doppler sonography (TCD) after oral premedication associating clonidine (2
      micrograms.kg-1) and flunitrazepam (70 micrograms.kg-1) in patients scheduled for
      carotid stenosis surgery. STUDY DESIGN: Prospective study, not randomized, the
      patient being his own "control". PATIENTS AND METHODS: Thirteen patients
      undergoing carotid endarterectomy under cervical plexus block were included. The
      monitoring included: automated arterial pressure cuff, ECG, radial artery
      catheter, TCD with probe secured in temporal window. The study of the
      cerebrovascular CO2 reactivity was performed with TCD recording on the side of
      operation, on the day before, and on the day of carotid endarterectomy, 90 min
      after the premedication, immediately before surgery. To change PaCO2, four
      ventilatory states were successively performed: (1) normoventilation, (2)
      hyperventilation, (3) hypoventilation, (4) "breath-holding test". At each state,
      it was noted: HR, MAP, PaCO2, mean blood flow velocity in the middle cerebral
      artery (Vm-MCA), resistance index of Pourcelot (RI), cerebrovascular reactivity
      (slope Vm-MCA/PaCO2). The results (+/- SEM) were analyzed by Wilcoxon test or t
      test. RESULTS: After premedication, cerebrovascular CO2 reactivity decreased
      (0.043 +/- 0.019 vs 0.034 +/- 0.013; p < 0.05) without modification of RI (0.578
      +/- 0.291 vs 0.612 +/- 0.025; NS). No complication during carotid clamping was
      reported. CONCLUSION: Inclusion of clonidine in premedication before carotid
      stenosis surgery must be questioned because a decrease of cerebrovascular CO2
      reactivity could be deleterious in case of intraoperative stroke.

PMID- 11530749
TI  - [Pulmonary diffusion of antibiotics. Critical analysis of the literature].
AB  - OBJECTIVES: Collect exhaustive data from the literature concerning the diffusion
      of antibiotics into lung tissue and calculate their inhibitory quotient towards
      the germs most frequently encountered in pulmonary infections. DATA SOURCES:
      Review of the literature. Data collected from the Medline database with the key
      words: lung, diffusion, disposition, antibiotics. Inhibitory quotients calculated
      from these data. RESULTS: The results were relatively similar for the different
      types of samples, though some differences existed between the studies. These
      differences were caused in particular by methodological difficulties for the
      tissue dosage of antibiotics. CONCLUSION: Further standardized studies, measuring
      in particular the antibiotic concentration in the epithelial lining fluid and in
      the alveolar macrophages, are necessary to obtain more reliable results in terms
      of inhibitory quotients. Only clinical studies, perhaps with the help of these
      data, could establish the real efficiency of antibiotics in lung infections.

PMID- 11530750
TI  - [Transesophageal echocardiography and air embolism during posterior fossa
      neurosurgery. Intraoperative detection in the foramen ovale].
AB  - Sitting position during neurosurgery is discussed because the risk of venous air
      embolism and paradoxical air embolism is increased. Preoperative transoesophageal
      echocardiography is proposed to screen patients with patent foramen ovale to
      avoid them for the sitting position. This work reported 2 patients in conflict
      with this screening. It is discussed the physiological principles governing the
      paradoxical air embolism and the actual recommended monitoring for this position.

PMID- 11530751
TI  - [Mastocytosis: general anesthesia with remifentanil and sevoflurane].
AB  - Mastocytosis is a disorder with potential anaesthesia complications. Reviewing
      the literature, anaesthetic management of mastocytosis is controversial. We
      report the successful use of remifentanil and sevoflurane in a woman with
      systemic mastocytosis. No reaction nor histamine release was observed in these
      cases.

PMID- 11530752
TI  - [Goiter and pregnancy: a cause of predictable difficult intubation].
AB  - During pregnancy the thyroid undergoes several changes including altered function
      and gland enlargement. We describe the management of a 36-week pregnant woman
      presenting with upper-way obstruction secondary to tracheal compression by a
      large multinodular goitre. The patient was successfully managed with an awake
      fibreoptic intubation performed orally followed by a caesarean section and
      thyroidectomy as a combines procedure.

PMID- 11530753
TI  - [Ilio-inguinal Ilio-hypogastic nerve block with a single puncture: an alterantive
      for anesthesia in emergency inguinal surgery].
AB  - The authors describe the anaesthetic procedure for a strangulated hernia repair
      needing resection and anastomosis of the small bowel in an adult patient. This
      procedure was performed with an ilio-inguinal/ilio-hypogastric nerve block
      according to a paediatrical simplified technique with a single puncture. For this
      patient who had relative contraindications for central blocks, this regional
      technique allowed to avoid general anaesthesia with its gastric aspiration and
      predictible difficult intubation risks. This block associated with a very light
      sedation was sufficient for all the surgical procedure, and postoperative
      analgesia was efficient over 3 hours. This simplified nerve block, better than
      the conventional approach for the clinical practice, represents a recommended
      alternative for hernia repair in emergency for high risk patients who could have
      a general anaesthesia or a central block.

PMID- 11530754
TI  - [Anesthetic malignant hyperthermia and multiple organ dysfunction syndrome].
AB  - The typical explosive form of malignant hyperthermia caused by following
      isoflurane anaesthesia is a well-known phenomenon. Nevertheless, since dantrolene
      is used, its evolution toward a multiple organ failure has been rarely described.
      We report a case of typical explosive malignant hyperthermia caused by an
      isoflurane anaesthesia complicated by a cardiovascular failure, a disseminated
      intravascular coagulation, an acute liver failure and an acute renal failure.
      Afterwards, muscle weakness of the right calf was the only aftermath.

PMID- 11530755
TI  - [Acute rhabdomyolysis after spinal anesthesia for knee arthroscopy].
AB  - We report an observation of acute rhabdomyolysis of gluteus maximum muscles
      occurring in a non-obese patient installed in supine position that underwent knee
      arthroscopy under spinal anaesthesia. The patient had insulin-dependent diabetes
      melitus with documented microangiopathy. The interest of this observation resides
      in the occurrence of the syndrome after a short period of time (one hour) of
      installation in the supine position in a patient that did not have any of the
      generally described risk factors of rhabdomyolysis.

PMID- 11530756
TI  - [When the combined crural and sciatic block become unavoidable].

PMID- 11530757
TI  - [Intraoperative gas embolism].

PMID- 11530758
TI  - [Complications arising from occasional consumption of ecstasy].

PMID- 11530759
TI  - Case management: Part 2--Clarifying roles and gathering resources.

PMID- 11530760
TI  - A framework for consultants' recommendations: helping your organization to
      accurately assess social work effectiveness.

PMID- 11530761
TI  - When enough is enough: ethical management of the chronically nonadherent patient.

PMID- 11530762
TI  - Dealing with difficult patients: one institution's response.

PMID- 11530763
TI  - The psychosocial issues of children with perinatally acquired HIV disease
      becoming adolescents: a growing challenge for providers.
AB  - Today, providers caring for children who have perinatally acquired HIV disease
      treat them differently than they did less than a decade ago. As our knowledge of
      HIV and its treatment have grown, so have we and so have our children. We are
      seeing the first wave of adolescents with perinatally acquired HIV disease. This
      increased longevity has given new meaning to past challenges such as treatment
      regimens, medication adherence, disclosure, and permanency planning previously
      faced by providers, children, and their families. New challenges, such as
      adolescent treatment decisions, relationships, intimacy, college, and careers
      have been added to the list. As a prediatric nurse practitioner having "grown up"
      with perinatally acquired HIV disease in the last decade, I reflect on past
      challenges and offer a perspective on those that lie ahead. A multidisciplinary,
      family-centered support group intervention that was developed at our AIDS Center
      Program to assist families, older children, adolescents, and providers in facing
      these challenges is described.

PMID- 11530764
TI  - Case report. Diagnosis of early HIV-1 infection.
AB  - The diagnosis of acute infection with human immunodeficiency virus (HIV) presents
      a challenge for the primary care provider. We present a case of early HIV
      infection and discuss the limitations of the currently established diagnostic
      algorithm for HIV infection. We conclude that alternative diagnostic testing for
      human immunodeficiency virus type 1 (HIV-1) RNA is warranted in certain clinical
      settings. Appropriate, early diagnosis of HIV infection may improve the patient's
      outcome and provide additional public health benefits by reducing transmission of
      disease.

PMID- 11530765
TI  - HIV prevention in primary care: impact of a clinical intervention.
AB  - Discomfort, lack of confidence in skills, and environmental constraints may cause
      primary care providers to miss opportunities to discuss human immunodeficiency
      virus (HIV) risk with patients. We used a systems approach to address both
      intrapersonal and environmental barriers to HIV risk assessment and prevention
      counseling in a managed care clinical setting. The design was one-group
      pretest/posttest. The study took place in two primary care clinics of a large
      Pacific Northwest managed care organization. Participants (n = 49) included
      physicians, physician assistants, nurse practitioners, registered nurses, and
      social workers. The intervention included training, clarification of
      provider/staff roles, assess to tools and materials, and reminders/reinforcers.
      Outcome measures were provider attitudes, beliefs, outcome expectations,
      knowledge, confidence in skills, and perceived supports and barriers, measured by
      written pretest/posttest surveys administered 12 months apart. Seven months after
      the most intensive part of the intervention, providers' attitudes and beliefs
      were more favorable to HIV risk assessment and prevention counseling. They were
      less likely to express frustration with high-risk patients (decrease from 100% to
      79% agreement, p = 0.001) and more confident that their advice would be effective
      with gay men and single adult heterosexuals (p = 0.002 and 0.005, respectively).
      They reported more confidence in their training in sexual history taking (p =
      0.0003) and their skills assessing readiness for change (p = 0.007), and more
      support in practice environments. This study demonstrated that it is possible to
      affect important personal and environmental factors that influence primary care
      providers' HIV prevention behavior using an interactive, real-world systems
      approach. Further research is needed on providers' impact on patient behavior.

PMID- 11530766
TI  - AIDS in India: incidence, prevalence, and prevention,.
AB  - With 3.7 million human immunodeficiency virus (HIV)-positive in India, many
      predict that this nation of 1 billion people will soon see infection rates soar
      if successful prevention programs are not implemented. The majority of infections
      occur through sexual contact, with blood banks, intravenous drug use, and mother
      to-child transmission also spreading the virus. Those in India who are HIV
      positive are highly stigmatized and often have difficulty finding physicians who
      are willing to treat them. Nongovernment organizations provide various services,
      including physician referrals and legal help for those who are HIV-positive and
      programs to raise awareness and education. Although the Government of India has
      designed various programs to help prevent the further spread of HIV, lack of
      funding and poor regulatory systems are further barriers to their implementation.
      India is also at war with poverty, illiteracy, and gender inequality, all of
      which make the fight against acquired immune deficiency syndrome (AIDS) a more
      difficult battle. India's AIDS control strategy must take these issues into
      account in order to design successful programs to prevent infection rates from
      multiplying rapidly.

PMID- 11530767
TI  - Successful prophylaxis against Pneumocystis carinii pneumonia in HIV-infected
      children using smaller than recommended dosages of trimethoprim-sulfamethoxazole.
AB  - Prophylaxis against Pneumocystis carinii pneumonia (PCP) is an essential part of
      the management of children with human immunodeficiency virus (HIV) infection and
      acquired immune deficiency syndrome (AIDS). No dose-ranging studies were ever
      performed; therefore, the amount of trimethoprim-sulfamethoxazole (TMP-SMX)
      needed to suppress PCP in children with HIV/AIDS is not known. The dose
      recommended by the Centers for Disease Control (CDC) has been thought to be just
      above the threshold needed for prevention, based on anecdotal breakthrough PCP in
      cancer patients who were improperly dosed. We have been giving prophylaxis based
      on body weight rather than surface area, and this, combined with growth of our
      children, has led to a large experience with dosages lower than the currently
      recommended 150 mg/m2. The medical records of children with HIV who met CDC
      guidelines for institution of PCP prophylaxis were reviewed. To ascertain the per
      square meter (m2) dosage each child was receiving, body surface area was
      calculated from height and weight measurements. Dosages were recalculated every 6
      months and at each dosage change. Data regarding PCP infection, bacterial
      infections, and side effects of TMP-SMX were extracted. Data were compiled from
      1,719.5 child-months of TMP-SMX prophylaxis, including 1,532.5 child-months below
      the currently recommended dose. Sixty-seven percent of our child-months were at
      or below two-thirds the CDC recommended dose. There were no cases of proven or
      suspected PCP. Incidence of other serious bacterial infections was low.
      Bacteremia and sepsis with Streptococcus pneumoniae was the most common proven
      bacterial infection, at a rate of 5.5 episodes per 100 child-years. The incidence
      of bacterial infection did not vary by the dose of TMP-SMX. TMP-SMX prophylaxis
      was well tolerated; most reactions were mild and self-limited and did not recur
      with re-institution of the drug. Only 6.1% of this cohort had TMP-SMX prophylaxis
      discontinued due to perceived toxicity. These data show that the currently
      recommended dose of TMP-SMX (150 mg/m2) may not be required to prevent PCP in
      children with HIV/AIDS. The drug is well tolerated at all dosage levels. The
      incidence of serious bacterial infection in this cohort of patients did not
      depend upon the amount of TMP-SMX prescribed. A prospective, controlled clinical
      trial of low-dose TMP-SMX for children with HIV infection is warranted.

PMID- 11530768
TI  - Lack of prior antiretroviral therapy is associated with increased mortality among
      hospitalized patients with AIDS in Sao Paulo, Brazil,.
AB  - The death rate in adults with acquired immune deficiency syndrome (AIDS) at the
      Institute of Infectious Diseases "Emilio Ribas" in Sao Paulo City has decreased
      significantly from 29% in 1995 to 19.8% in 1999, and hospitalization time has
      been reduced by 4 days in the period from 1998 to 1999. Lack of antiretroviral
      treatment (ART) before hospitalization was associated with death during
      hospitalization (odds ratio [OR] = 3.8), and survival was associated with
      previous use of three or more antiretrovirals (OR = 0.15). Therefore, we
      recommend an aggressive campaign for human immunodeficiency virus (HIV) antibody
      screening among the at-risk populations in Brazil to assure that ART is provided
      when necessary.

PMID- 11530769
TI  - Factors affecting total hospital charges and utilization for South Carolina
      inpatients with HIV/AIDS in 1994-1996,.
AB  - This study's analysis addresses trends in hospital utilization and costs for
      patients with human immunodeficiency virus acquired immunodeficiency syndrome
      (HIV/AIDS) from 1994 through 1996 in South Carolina, as well as the effect of
      patient sociodemographics, referrals, and provider characteristics. This is a
      population-based study of all emergency department visits and hospitalizations
      occurring during that time period. The total hospital charge per patient
      significantly increases over time, while the total inpatient days per patient
      decreases significantly, and the charge per day increases significantly. The
      proportion of patients with public insurance or who are indigent is increasing,
      and the proportion of those with private insurance is decreasing. Other variables
      that have a significant impact on total hospital charges, total inpatient days,
      and charges per day are types of insurance, physicians specialty, discharge
      status, and number of diagnoses (severity). Persons who are Medicare eligible are
      sicker and have higher hospital costs and more inpatient days when compared to
      those with Medicaid. Intensity of services (hospital charges per day) is
      associated with private insurance and self-pay patients. Persons with terminal
      illness stay longer and have higher costs. When HIV/AIDS is the primary admitting
      diagnosis, there are higher hospitalization costs. Increasing severity of illness
      (number of diagnoses) leads to higher total hospital charges and days. With the
      introduction of new AIDS treatments in 1996, further study is required to
      determine the effects of new drugs, physician specialties, and other provider
      characteristics on the cost and utilization of health care services, both
      inpatient and outpatient.

PMID- 11530770
TI  - Encouraging results for tenofovir.

PMID- 11530771
TI  - HAART less costly.

PMID- 11530772
TI  - Adherence device developed.

PMID- 11530773
TI  - Risk of contracting HIV.

PMID- 11530774
TI  - Vaccine enters human trials.

PMID- 11530775
TI  - Canada's physician workforce also aging.

PMID- 11530776
TI  - Aramark profile: Andreas Laupacis. Interview by Cynthia Martin.

PMID- 11530778
TI  - Keystone clocks.

PMID- 11530779
TI  - Physiological responses to oxidative and heavy metal stress in seedlings of rice
      paddy.

PMID- 11530780
TI  - Serum cholesterol and haemorrhagic stroke.

PMID- 11530781
TI  - [Is there a role for rectal conservation in familial adenomatous polyposis?].

PMID- 11530782
TI  - Review of the NEPSY: a developmental neuropsychological assessment.

PMID- 11530783
TI  - Death of Donald D. Tresch.

PMID- 11530784
TI  - High school students in postwar Lebanon: attitudes, information sources, and
      perceived needs related to sexual and reproductive health.

PMID- 11530785
TI  - Grossly false applanation tonometry associated with interface fluid in
      susceptible LASIK patients.

PMID- 11530786
TI  - Effect of ciprofloxacin and ofloxacin on bacterial flora.

PMID- 11530787
TI  - Noncontact tonometry after LASIK.

PMID- 11530788
TI  - Intraoperative corneal topography.

PMID- 11530789
TI  - Assessing surgically induced astigmatism.

PMID- 11530790
TI  - Subjective photic phenomena with refractive multifocal and monofocal IOLs.

PMID- 11530791
TI  - Neodymium: YAG laser membranotomy after extracapsular cataract surgery in
      diabetic patient.

PMID- 11530792
TI  - Is detailed preassessment a necessity for day-case phacoemulsification under
      local anesthesia?

PMID- 11530793
TI  - Clinical note concerning retrobulbar anesthesia.

PMID- 11530794
TI  - Consultation section. Cataract surgical problem.

PMID- 11530795
TI  - Retrotransposons rule in Carry-le-Rouet.

PMID- 11530796
TI  - Footprints of primordial introns on the eukaryotic genome.

PMID- 11530797
TI  - Cytokines and hematology.

PMID- 11530798
TI  - Upshaw-Schulman syndrome revisited: a concept of congenital thrombotic
      thrombocytopenic purpura.
AB  - Upshaw-Schulman syndrome (USS) is a congenital bleeding disorder characterized by
      repeated episodes of thrombocytopenia and microangiopathic hemolytic anemia that
      respond to infusions of fresh frozen plasma. Inheritance of USS has been thought
      to be autosomal recessive, because 2 siblings in the same family are often
      affected but their parents are asymptomatic. Recently, chronic relapsing
      thrombotic thrombocytopenic purpura (CR-TTP), reported almost exclusively in
      adults, was shown to be caused by inherited or acquired deficiency in the
      activity of a plasma von Willebrand factor-cleaving protease (vWF-CPase). The
      pathogenesis of USS is unknown, and a relationship between CR-YEP and USS has not
      been reported. We studied 3 unrelated USS patients (ST, SY, and KI) who presented
      with severe indirect neonatal hyperbilirubinemia. All 3 patients had undetectable
      vWF-CPase activity, and the inhibitors to vWF-CPase were all negative. In their
      parents with no clinical symptoms, vWF-CPase activities as a percentage of
      control samples (mother/father) were 17/20 for ST, 60/45 for SY, and 36/5.6 for
      KI. Thus, USS and vWF-CPase activity appear to be coinherited as autosomal
      recessive traits. Transfusion of fresh frozen plasma in 2 patients (ST and SY)
      resulted in the expected maximal increment of approximately 7% to 8% in vWF-CPase
      activity at 1 to 4 hours, but the levels became less than 3% within 2 days. After
      this decrease, platelet counts increased, plateaued in the normal range at 10 to
      12 days, and declined thereafter. Thus, the 2 to 3 weeks of therapeutic benefit
      from plasma infusions will be discussed in relation to the intravascular lifetime
      of vWF-CPase.

PMID- 11530799
TI  - Deficient activity of von Willebrand factor-cleaving protease in patients with
      Upshaw-Schulman syndrome.
AB  - We identified unusually large von Willebrand factor (vWF) multimers caused by
      deficient activity of vWF-cleaving protease in 2 patients with Upshaw-Schulman
      syndrome. The autoantibodies that inhibited the protease activity were not
      detected in the plasma of either patient. Periodic fresh-frozen plasma
      transfusion was effective for management of the hemolysis and thrombocytopenia.
      We detected enriched enzyme activity in a particular plasma fraction, although
      molecular cloning of this specific protease is needed to determine a more
      detailed pathogenesis and to develop new therapeutic approaches.

PMID- 11530800
TI  - Transforming growth factor beta, pleiotropic regulator of hematopoietic stem
      cells: potential physiological and clinical relevance.
AB  - Transforming growth factor beta (TGF-beta) is a pleiotropic regulator of all
      stages of hematopoieis. Depending on the differentiation stage of the target
      cell, the local environment, and the concentration of TGF-beta, TGF-beta can be
      proproliferative or antiproliferative, proapoptotic or antiapoptotic, and/or
      prodifferentiative or antidifferentiative. TGF-beta is the major regulator of
      stem cell quiescence and can act directly or indirectly through effects on the
      marrow microenvironment. In addition, paracrine and autocrine actions of TGF-beta
      have overlapping but distinct regulatory effects on hematopoietic stem/progenitor
      cells. Neutralization of autocrine TGF-beta has therapeutic potential.

PMID- 11530801
TI  - Cytokines in graft-versus-host disease and the graft-versus-leukemia reaction.
AB  - Graft-versus-host disease (GVHD) is the major complication after allogeneic
      hemopoietic stem cell transplantation. GVHD is destructive by itself and sets the
      stage for other sequelae, in particular, overwhelming infections. Recent
      investigations have improved our understanding of the underlying pathophysiology
      of GVHD. There are now compelling data on the role of host tissue destruction as
      the initial insult, extensive interactions of cellular donor and host components,
      a complex network of cytokines, adhesion molecules, and other components in the
      development of GVHD. The improved understanding of interactions among various
      signals is likely to allow for the development of new prophylactic strategies. A
      review of the data shows, however, that results are very dependent upon the
      models used. It is difficult or impossible to separate completely the discussion
      of cytokines that affect hemopoietic cells from discussion of cytokines that
      exert effects on immune cells. Furthermore, secondary effects on immune cells via
      hemopoietic cells complicate the picture. Application of the principles of
      cytokine signaling to the clinical setting may necessitate new trial design
      structures that take into consideration donor and host characteristics as well as
      the kinetics of GVHD development.

PMID- 11530802
TI  - Cytokines: past, present, and future.
AB  - This review provides an historical account of the discovery and development of
      cytokines. Cytokines are soluble extracellular proteins or glycoproteins that are
      crucial intercellular regulators and mobilizers of cells engaged in innate as
      well as adaptive inflammatory host defenses, cell growth, differentiation, cell
      death, angiogenesis, and development and repair processes aimed at the
      restoration of homeostasis. Although cytokines are occasionally produced
      constitutively, they are usually produced by virtually every nucleated cell type
      in response to injurious stimuli. Cytokines act on cells expressing complementary
      receptors. Cytokines have been assigned to various family groups based on the
      structural homologies of their receptors. This review shows how cytokine research
      evolved from phenomenological to molecular stages and from a focus on ligands to
      characterization of cytokine receptors. The advent of molecular biology,
      monoclonal antibodies, and microsequencing made it possible to obtain pure
      recombinant cytokine preparation for experimental and therapeutic applications.
      The development of targeted gene deletions revealed many cytokines to have
      unexpected pathophysiological functions. The identification of "virokines,"
      homologues that mimic cytokine ligands and receptors, has provided impetus to the
      founding of biotechnology companies aimed at developing cytokine agonists and
      antagonists for therapeutic applications. The discipline of cytokinology is now
      endowed with several journals, multiple annual meetings, and many devoted
      investigators. The explosion in cytokine information over the past 40 years has
      been enormous and full of surprises. If past be prologue, with the advent of
      genomics and proteomics the future should witness even greater progress.

PMID- 11530804
TI  - Proliferative capacity of single isolated CD34+ hematopoietic stem/progenitor
      cells in paroxysmal nocturnal hemoglobinuria.
AB  - Paroxysmal nocturnal hemoglobinuria (PNH) results from somatic mutations of the X
      linked PIG-A (phosphatidylinositol glycan-class A) gene, which occurs on a
      hematopoietic stem cell level, leading to a proportion of blood cells being
      deficient in all glycosylphosphatidylinositol (GPI)-anchored surface proteins.
      Although these GPI-deficient cells can explain many of the clinical symptoms of
      PNH, the pathogenesis of PNH is still somewhat obscure and many questions remain.
      To assess the hematopoietic defect involved in PNH, CD34+ CD59+ (normal phenotype
      hematopoietic stem/progenitor) and CD34+ CD59- (PNH phenotype) cells from PNH
      patients (n = 16) and CD34+ CD59+ cells from healthy volunteers (n = 10) were
      sorted as single cells into 96-well flat-bottom culture plates containing culture
      medium supplemented with stem cell factor, interleukin (IL)-3, erythropoietin,
      granulocyte-macrophage-colony-stimulating factor (GM-CSF), G-CSF, IL-6,
      thrombopoietin, and Flt-3 ligand. We found that the single PNH CD34+ CD59- cells
      had a growth advantage over the single CD34+ CD59+ cells to some extent, but they
      both had impaired growth abilities compared with CD34+ cells from healthy
      volunteers.

PMID- 11530803
TI  - Current knowledge on the pathophysiology of Fanconi anemia: from genes to
      phenotypes.
AB  - Fanconi anemia (FA) is an autosomal recessive disease characterized by congenital
      anomalies, bone marrow failure, and leukemia susceptibility. FA cells show
      chromosome instability and hypersensitivity to DNA cross-linking agents such as
      mitomycin C. Recent studies indicate that there are at least 8 genetically
      distinct FA groups (A, B, C, D1, D2, E, F, G). To date, 6 genes (for A, C, D2, E,
      F, and G) have been cloned. In this review, we describe the structures and
      functions of FA proteins. Increasing evidence indicates that the multiple FA
      proteins cooperate in a biochemical pathway and/or a multimer complex. FANCD2, a
      downstream component of the FA pathway, has recently been shown to be
      ubiquitinated in response to DNA damage and to translocate to nuclear foci
      containing BRCA1, a breast cancer susceptibility gene product, suggesting a role
      for this protein in DNA repair functions. We also describe 2 emerging issues:
      genotype-phenotype relationships and mosaicism. The FA pathway is likely to play
      a critical role as a caretaker of genomic integrity in hematopoietic stem cells.
      Clarifying the molecular basis of this disease may provide new insights into the
      pathogenesis of bone marrow failure syndromes and myeloid malignancies.

PMID- 11530805
TI  - Involvement of the NUP98 gene in a chromosomal translocation t(11;20)(p15;q11.2)
      in a patient with acute monocytic leukemia (FAB-M5b).
AB  - We report here a case of acute monocytic leukemia (M5b subtype according to the
      French-American-British [FAB] classification) with chromosomal translocation
      t(11;20)(p15;q11.2). Fluorescence in situ hybridization analysis with a probe for
      the NUP98 gene, which is located at chromosome band 11p15, showed that the probe
      hybridized to both derivative chromosomes 11 and 20 as well as to the remaining
      normal chromosome 11, indicating that the NUP98 gene was split and involved in
      this translocation. This is the first report of t(11;20)(p15;q11.2) involving the
      NUP98 gene in overt leukemia.

PMID- 11530806
TI  - A variant form of myelodysplastic syndrome with Ph- minor-BCR/ABL transcript.
AB  - This study concerns a patient with minor (m)-BCR/ABL transcript-positive and
      Philadelphia (Ph) chromosome-negative myelodysplastic syndrome (MDS). The patient
      was a 78-year-old man whose condition was diagnosed as refractory anemia with
      excess of blasts in transformation. Molecular genetic studies, using reverse
      transcriptase polymerase chain reaction analysis detected m-BCR/ABL messenger
      RNA. We used spectral karyotyping to analyze metaphase cells but could not detect
      a Ph chromosome. Fluorescence in situ hybridization, however, revealed fusion
      signals of BCR and ABL probes on an apparently normal chromosome 22.

PMID- 11530807
TI  - Myelodysplastic syndrome progresses rapidly into erythroleukemia associated with
      synchronous double cancers of the stomach and the papilla of Vater.
AB  - Patients with myelodysplastic syndrome (MDS) show a relatively high incidence of
      developing cancers. However, it is extremely rare that synchronous double cancers
      develop in an MDS patient. We report a case of MDS that progressed rapidly into
      erythroleukemia (M6 by French-American-British classification) complicated by
      gastric cancer and carcinoma of the papilla of Vater. A 66-year-old man was
      admitted because of pancytopenia with peripheral blasts. A diagnosis of MDS (with
      refractory anemia with excess of blasts in transformation [RAEB-T]) was made by
      bone marrow examination. Chromosome analysis revealed 46,XY. An early gastric
      cancer was also diagnosed by endoscopic examination. The peripheral blasts
      gradually proliferated and the disease progressed to M6. A chromosome abnormality
      46,XY,del(1)(q42) was detected at the leukemic transformation. A CAG (low-dose
      cytarabine and aclarubicin in combination with granulocyte colony-stimulating
      factor) regimen was started as a remission-induction therapy. However,
      obstructive jaundice developed and a marked dilatation of bile ducts was observed
      by abdominal computed tomography (CT). A carcinoma of the papilla of Vater was
      detected by endoscopy. As remission was achieved and the pancytopenia improved,
      the patient subsequently underwent a surgical jejuno-choledochostomy to manage
      the jaundice. However, the leukemia relapsed thereafter and additional chromosome
      abnormalities including der(5)t(5;10)(p15:q11) were observed.

PMID- 11530808
TI  - Successful treatment with a chimeric anti-CD20 monoclonal antibody (IDEC-C2B8,
      rituximab) for a patient with relapsed mantle cell lymphoma who developed a human
      anti-chimeric antibody.
AB  - Mantle cell lymphoma (MCL) has a poor prognosis without cure; the median overall
      survival ranges only from 3 to 4 years irrespective of conventional therapeutic
      regimens. IDEC-C2B8 (rituximab), a chimeric monoclonal antibody against the B
      cell-specific antigen CD20, induces an evaluable clinical response in patients
      with MCL with mild toxicities. However, the single agent rituximab cannot cure
      MCL. Due to its low immunogenicity, an antibody against IDEC-C2B8 (human
      antichimeric antibody [HACA]) has rarely been produced in vivo. We report a
      patient with relapsed MCL who was successfully treated with IDEC-C2B8 for over a
      year although she developed HACA 6 months after the initial administration of
      IDEC-C2B8 in the phase II clinical trial conducted by Zenyaku Kogyo Co. Ltd. We
      followed the pharmacokinetics of IDEC-C2B8, the serum HACA titer, and the number
      of B lymphocytes in the peripheral blood in relation to clinical response. The
      HACA became undetectable soon after subsequent administrations of IDEC-C2B8. When
      the serum level of IDEC-C2B8 was kept elevated, clinical responses were
      apparently observed and HACA disappeared during this response period. There were
      no significant clinical toxicities related to the appearance of HACA. The present
      findings suggested that IDEC-C2B8 is effective and safe even in patients who have
      developed HACA.

PMID- 11530809
TI  - Waldenstrom's macroglobulinemia associated with AA amyloidosis.
AB  - It is widely accepted that amyloidosis in Waldenstrom's macroglobulinemia (WM) is
      exclusively due to amyloid light-chain deposition. However, only a small number
      of previous reports have actually characterized the type of amyloid in WM. We now
      report the third patient with WM and amyloid A protein (AA) amyloidosis. This
      patient developed malabsorption, nephrotic syndrome, and orthostatic hypotension.
      AA was immunohistochemically demonstrated in the rectal biopsy. In conjunction
      with previous examples of AA amyloidosis, the present report raises the
      possibility that AA amyloidosis may also occur in WM patients.

PMID- 11530810
TI  - Influence of timing of administration of 5-fluorouracil to donors on bone marrow
      engraftment in nonmyeloablated hosts.
AB  - We evaluated the engraftment and the cell cycle status of marrow cells at various
      times after 5-fluorouracil (5-FU) administration. 5-FU (150 mg/kg) was given to
      donor male BALB/c mice at 1, 2, 6, or 12 days prior to marrow harvest. The donor
      cells were then assessed in host nonmyeloablated female mice. Bone marrow
      engraftment of marrow treated with 5-FU was evaluated and compared to marrow
      treated with diluent (phosphate-buffered saline) at 3 and 10 weeks after marrow
      infusion. Our data show a rapid induction of an engraftment defect 1 day after 5
      FU, persistence of this defect through day 6, and a recovery by day 12.
      Experiments using hydroxyurea (which selectively kills cells in the S phase) to
      determine the cell cycle status indicated that cells that engrafted in post-5-FU
      marrow were noncycling at days 1, 2, and 12 but cycling at day 6. Post-5-FU bone
      marrow was also analyzed in vitro by colony assays and its cycling status
      determined by 3H-thymidine suicide assay. High-proliferative-potential colony
      forming cells (HPP-CFCs) and low-proliferative-potential colony-forming cells
      (LPP-CFCs) decreased rapidly 1 day after 5-FU, with a nadir observed at day 6 for
      HPP-CFCs and day 2 for LPP-CFCs. By day 12, LPP-CFCs showed a total recovery, but
      HPP-CFCs were still defective. Significant numbers of HPP-CFCs were cycling,
      mostly at days 6 and 8 after 5-FU, whereas LPP-CFCs appeared quiescent except at
      day 2. These results emphasize the importance of timing if post-5-FU marrow is
      used for gene therapy or marrow transplantation.

PMID- 11530811
TI  - Repetitious appearance and disappearance of different kinds of clonal cytogenetic
      abnormalities after allogeneic bone marrow transplantation.
AB  - We report a childhood case that showed the repeated appearance and disappearance
      of various kinds of cytogenetic abnormalities (CA) for 5.5 years after allogeneic
      bone marrow transplantation (BMT). The patient underwent allogeneic BMT from an
      HLA-matched unrelated donor during the second complete remission of acute
      lymphoblastic leukemia. The conditioning regimen for BMT consisted of etoposide,
      cyclophosphamide, anti-human thymocyte immunoglobulin, and total body
      irradiation. There were no leukemic relapses or secondary acute myeloid
      leukemia/myelodysplastic syndrome (AML/MDS) since the BMT. The CA occurred from
      residual recipient cells, which were damaged by chemotherapy or radiation prior
      to BMT. Although previous studies about post-BMT CA had reported the continuous
      emergence of identical clones, the present case showed the appearance of one
      different type of clone after another. Although the appearance of different types
      of CA may mean that these clones did not obtain any growth advantages, it may be
      a sign of genomic instability, which is probably a risk factor for the
      development of secondary AML/MDS.

PMID- 11530812
TI  - Regulation of hematopoiesis by chemokine family members.
AB  - Chemokines, originally designated as chemoattractant cytokines, comprise a large
      family of molecules that have been implicated in a number of different functions
      mediated through chemokine receptors. Among these functions are regulatory roles
      in hematopoiesis that encompass effects on the proliferation, survival, and
      homing/migration of myeloid progenitor cells. This article reviews the field of
      chemokine regulation of hematopoiesis at the level of myeloid progenitor cells.

PMID- 11530813
TI  - Pneumococcal arthritis affects performance status in patients with chronic GVHD
      of the skin following allogeneic bone marrow transplantation.
AB  - We encountered 2 patients with pneumococcal arthritis following bone marrow
      transplantation (BMT). Both patients received grafts from unrelated human
      lymphocyte antigen (HLA)-matched donors and had suffered from chronic graft
      versus-host disease (GVHD). One, a 10-year-old boy, suffered from Epstein-Barr
      virus-related lymphoproliferative disease (EB-LPD) and received oral 6
      mercaptopurine and methotrexate to manage lymphadenopathy. Twenty-four months
      after BMT and 7 months after the onset of EB-LPD, pneumococcal arthritis occurred
      in both knee joints. The other patient, a 10-year-old girl, received multiagent
      immunosuppressive therapy for her chronic GVHD. At 51 months following BMT,
      pneumococcal arthritis occurred in her left knee joint. Chronic GVHD of the skin
      delayed the recovery from the arthritis in both patients. This complication is
      quite rare but can be very serious, in regard to the patient's performance status
      following BMT. Although vaccination against pneumococcus or preventive
      antibiotics should be administered to high-risk patients, early diagnosis and
      treatment may be the best strategy for pneumococcal arthritis.

PMID- 11530814
TI  - Lethal adenovirus infection in a patient who had undergone nonmyeloablative stem
      cell transplantation.
AB  - We present a case of adenovirus (ADV) infection in a patient who had undergone
      nonmyeloablative stem cell transplantation (NST). A 50-year-old man with chronic
      myelogenous leukemia in the second chronic phase underwent NST from an HLA 2-loci
      mismatched sibling. ADV hemorrhagic cystitis developed and progressed to lethal
      pneumonia. ADV was isolated from urine, bronchoalveolar lavage fluid, and
      postmortem specimens of kidney and liver. Because there are few reports of lethal
      pneumonia associated with ADV in Japan, we present the case and discuss the cause
      of and therapy for the infection.

PMID- 11530815
TI  - The effect of oxygen on retinal degeneration in wild-type and hsp70.1 knockout
      neonatal retinal degeneration mice.
AB  - The present study examined the effect of oxygen on photoreceptor degeneration in
      the retina of heat shock protein 70.1 (hsp70.1) knockout type and wild-type
      retinal degeneration (rd) mice. All the neonatal rd mice were exposed to
      hyperoixa for 5 days after birth, and then were returned to room air before being
      sacrificed. At the postnatal 10, 14, 18, and 21 days, the ratio of outer nuclear
      layer (ONL) thickness to total retinal thickness was compared between hsp70.1
      knockout type and wild type. The retina was also examined for DNA fragmentation
      by TdT-mediated biotin-dUTP nick-end labeling (TUNEL). In hsp70.1 knockout type,
      the ratio of ONL to total retinal thickness was higher than that in the wild type
      at each time. There was the remarkable difference in the number and distribution
      of TUNEL-positive cells between hsp70.1 knockout type and wild type rd mice. In
      conclusion, an oxygen-induced modulation of the rate of photoreceptor
      degeneration was more marked in the hsp70.1 knockout type than wild type rd mice.

PMID- 11530816
TI  - Comparison of the short-term clinical results of silicone and acrylic intraocular
      lens in patients with diabetes mellitus.
AB  - In order to compare the clinical results of silicone intraocular lenses (IOLs)
      and acrylic IOLs in patients with diabetes mellitus (DM), we reviewed the records
      of 69 diabetic patients (79 eyes--40 eyes; silicone IOLs, 39 eyes; acrylic IOLs)
      who had undergone phacoemulsifications and posterior chamber intraocular lens
      (PCI) implantations between January 1994 and January 1999. Postoperative ocular
      examinations included measurements of uncorrected and best corrected visual
      acuity tests and recording any complication one day, one week and two months
      after surgery. There was no statistically significant difference in visual acuity
      between the eyes with silicone IOLs and those with acrylic IOLs. Additionally,
      there was no difference in visual acuity according to the method of blood sugar
      level control. The rate of posterior capsular opacity (PCO) was significantly
      lower in the patients with acrylic IOLs than in those with silicone IOLs
      (p<0.05). These results suggest that there is no difference in visual outcome
      between acrylic IOLs and silicone IOLs in patients with DM. However in view of
      the lower rates of PCO with acrylic IOLs, they may be a better choice for eyes in
      diabetic patients.

PMID- 11530817
TI  - Predictability for proper capsular tension ring size and intraocular lens size.
AB  - Predicting correct capsular tension ring size and intraocular lens size using
      measurements of lens diameter, corneal diameter, axial length and capsular bag
      diameters to determine anatomical relationships of post implantation capsular
      tension ring (CTR). The vertical and horizontal diameters of cornea and lens were
      measured in 62 human eyeballs supplied from the eye bank of the Catholic
      University. The relationship between corneal diameter and axial length was
      examined in 195 living human eyes. An extension of capsular bag diameter after
      implantation of CTR was measured in 19 pigs' eyes purchased from a slaughter
      house. The correlation between the lens diameter and the capsular bag diameter
      after CTR implantation was analyzed using linear regression. The average
      diameters (mean of horizontal and vertical diameters) of cornea and lens in human
      eyeball of postmortems (average age:69, ratio of male:female = 23:39) were
      11.59+/-0.42 mm for horizontal diameter, 9.54+/-0.27 mm, for vertical diameter.
      The average corneal diameters and axial lengths in living human eyes (average
      age: 62, ration of male:female = 84:111) were 11.63+/-0.53 mm for the cornea
      diameter, 24.48+/-2.10 mm, for cornea axial length. There is a statistically
      significant correlation between corneal diameter and axial length (correlation
      coefficient=0.788; p<0.001) and corneal diameter and lens diameter (correlation
      coefficient=0.711; p<0.001). In pigs' eyes, there is a relationship between lens
      diameter and capsular bag diameter after implantation of 11 mm CTR (correlation
      coefficient=0.684; p<0.001). In conclusion, axial length and corneal diameter may
      give surgeons a valuable clue to expected size of capsular bag and important
      parameters for selecting the correct sized CTR and IOL.

PMID- 11530818
TI  - Comparison of visual field defects between primary open-angle glaucoma and
      chronic primary angle-closure glaucoma in the early or moderate stage of the
      disease.
AB  - The visual field data (Humphrey C24-2) of early to moderate stage glaucoma
      between primary open-angle glaucoma (POAG) and chronic primary angle-closure
      glaucoma (PACG) patients was compared. Eleven POAG (11 eyes) and 14 chronic PACG
      patients (14 eyes) were matched with respect to age, sex, and disease severity.
      Although the mean deviation, pattern standard deviation, and short-term
      fluctuation were similar between the two groups, the mean corrected pattern
      standard deviation was higher in the POAG patients (p=0.048). When the numeric
      pattern deviation data (STATPAC II) was used for point-wise between-group
      comparisons, more depressed paracentral points were found in POAG patients.
      Different patterns were identified in visual field damages between the chronic
      PACG and POAG patients. The chronic PACG patients showed more generalized field
      loss than the POAG patients.

PMID- 11530820
TI  - A rare cause of unilateral upper and lower eyelid swelling: isolated conjunctival
      amyloidosis.
AB  - Amyloidosis is a term encompassing a group of disorders characterized by the
      extracellular deposition of a substance called amyloid in various tissues. A very
      rare cause of chronic ocular discomfort is amyloidosis. We treated a patient with
      the above complaint in whom both eyelids were diffusely swollen with no other
      chronic ophthalmic complaints. Transconjunctival biopsy revealed amyloidosis and
      was confirmed on congo-red staining. Since we are aware that surgical excision
      may cause eyelid cicatrisation or secondary xerophthalmia, we explained the pros
      and cons of surgery to the patient. In view of the 12-year history and lack of
      other symptoms, the patient preferred to be kept under observation. Follow-up at
      two years did not reveal any significant increase in the size of the swelling.
      Therefore, we recommend that in a patient with amyloidosis with no visual/ocular
      impairment, the condition should be left alone without surgical intervention.

PMID- 11530819
TI  - Refractive changes of congenital entropion and epiblepharon on surgical
      correction.
AB  - In order to investigate the refractive error, amblyopic frequency, and refractive
      change, if any, following recovery of cornea injury through surgery of
      epiblepharon and congenital entropion patients, we retrospectively reviewed the
      sex distribution, age at operation, chief complaints, preoperative and
      postoperative refractive errors, and best corrected visual acuity in 160
      previously operated patients. The average age at operation was 7.9 years. The
      preoperative best corrected visual acuity of 133 eyes (41.6%) was below 5/9.
      Ninety-five eyes (29.7%) were preoperative myopes above -1.0D; 77 eyes (24%) were
      hyperopes above +1.0D; and 163 eyes were astigmatic above -1.0D. Of 228 eyes that
      were followed up for more than one year, 66 eyes demonstrated a best corrected
      visual acuity of below 5/9. There was no significant difference in the change in
      corneal astigmatism following surgery between the group under the age of 7 and
      the group over the age of 7. However, the mean best corrected visual acuity at
      postoperative one year was 6/9, which was significantly different from the
      preoperative value (P=0.006). Concurrent postoperative glasses correction and
      amblyopic therapy is indicated because the incidence of refractive errors and
      amblyopia is higher in epiblepharon and congenital entropion.

PMID- 11530821
TI  - A case of glaucoma associated with Sturge-Weber syndrome and Nevus of Ota.
AB  - The Sturge-Weber syndrome consists of a unilateral port-wine hemangioma of the
      skin along the trigeminal distribution and is accompanied by an ipsilateral
      leptomeningeal angioma. Glaucoma is present in approximately half of the cases.
      The Nevus of Ota is a melanocytic pigmentary disorder, most commonly involving
      the area innervated by the trigeminal nerve. Elevated intraocular pressure, with
      or without glaucomatous damage, is observed in 10% of the cases. We report the
      first case of glaucoma associated with Sturge-Weber syndrome and Nevus of Ota in
      Korea.

PMID- 11530822
TI  - A case of anaerobic abscessed hydroxyapatite orbital implants.
AB  - The purpose of this report is to document an unusual case of implant infection in
      a patient who had undergone enucleation and hydroxyapatite orbital implant
      surgery. A 32-year-old woman presented with chronic orbital discomfort and
      discharge following a history of hydroxyapatite orbital implant surgery at
      another hospital 4 years previous. She exhibited profuse discharge with a yellow,
      creamy color and marked conjunctival chemosis. Granulation tissue was noted on
      the central conjunctival surface. Following the removal of the conjunctival
      granulation tissue, a central 3x5 mm conjunctival dehiscence was present with
      exposure of the hydroxyapatite implant. A culture of purulent drainage emanating
      from the exposed implant showed a growth of Clostridium acetobutylicum. Removal
      of the orbital implant was done. The implant was noted to be filled with pus.
      This case suggests that anaerobic infection may be suspected when the granulation
      tissue is observed and a discharge with a foul odor is found.

PMID- 11530823
TI  - Central islands after LASIK detected by corneal topography.
AB  - A central island is defined as a localized elevated area in corneal topography
      after excimer laser application for myopic correction. We experienced 15 cases of
      central islands developed 1 week after LASIK using VISX STAR on corneal
      topography. The uncorrected visual acuity and best corrected visual acuity were
      0.52 +/- 0.22, 0.66 +/- 0.25 in central islands group and 0.69 +/- 0.19, 0.78 +/-
      0.19 in control group at 1 week after LASIK. The visual acuity in control group
      was more improved statistically significantly than central islands group
      (respectively p = 0.01, p = 0.03). There was no statistical significance between
      the two groups, although the uncorrected visual acuity and best corrected visual
      acuity were somewhat more increased in control group at 2 months and 6 months
      after LASIK than in central islands group (respectively p = 0.06, p = 0.24 at 2
      months, p = 0.10, p = 0.17 at 6 months). On the changes of spherical equivalent
      after LASIK, both the central islands group and control group were in hyperopic
      state at 1 week after LASIK and were somewhat regressed to myopia at 2 months and
      6 months after LASIK. But there was no statistical significance between the two
      groups at different time points (respectively p = 0.15, p = 0.64, p = 0.67). In
      12 cases the central islands were disappeared spontaneously at 2 months, but in 3
      cases the central islands were remained 6 months after LASIK on corneal
      topography. In the one case of 3 cases the best corrected visual acuity was 0.5
      at 6 months after LASIK, but in the others the best corrected visual acuity was
      not different from the mean best corrected visual acuity. Most cases in LASIK,
      the central islands were dissapeared without specific treatments as in PRK. We
      suggest, in the case of central islands at 6 months after LASIK, that if the
      patient complain visual discomfort, monocular diplopia, haloes, or ghost images,
      central reablation with excimer laser should be considered.

PMID- 11530824
TI  - Ventricular energetics during mechanical ventilation and intraaortic balloon
      pumping--computer simulation.
AB  - Computer simulation of a cardiovascular system enabled us to predict the effects
      of simultaneous application of mechanical ventilation (MV) and intraaortic ballon
      pumping (IABP) on ventricular energetics. External work (EW), pressure-volume
      area (PVA), potential energy (PE) and cardiac mechanical efficiency (CME) were
      calculated. Nummerical simulation showed that changes of positive intrathoracic
      pressure have a considerable effect on left and right ventricular EW, PE, PVA and
      CME, whether IABP is used or not. The right ventricular energetics was much less
      influenced by systemic resistance (Ras) changes than the left ventricular one.
      Simultaneous application of IABP and MV showed a remarkable effect on left
      ventricular EW. The net result was reversed sensitivity to pulmonary resistance
      (Rap) and reduced sensitivity to Ras. PVA was generally reduced, while CME is
      increased by simultaneous presence of IABP and MV. The sensitivity of CME to Rap
      and Ras variation was diminished in this situation.

PMID- 11530825
TI  - Pathological analysis of myocardial cell under ventricular tachycardia and
      fibrillation based on symbolic dynamics.
AB  - Ventricular fibrillation (VF) is one of the most serious malignant arrhythmias
      usually resulting from immediate degeneration of ventricular tachycardia (VT). In
      order to analyse the nonlinear dynamics of the cardiac micro-mechanism under VT
      and VT rhythm, at the cellular level, myocardial cell action potentials are
      investigated under different rhythm, normal sinus rhythm, VT and VT. On the basis
      of nonlinear chaotic theory and symbolic dynamics, we put forward new
      definitions, complexity rate, etc, and obtained some useful properties for
      cellular electrophysiological analysis. The results of the experiments and
      computation show that the myocardial cellular signals under VT and VF rhythm are
      different kinds of chaotic signals in that the cardiac chaos attractor under VF
      is higher than that under VT. The analytical complexity theory has been promising
      in the clinical application.

PMID- 11530826
TI  - Unstable Morse Code recognition system with back propagation neural network for
      person with disabilities.
AB  - A Morse code auto-recognition system is limited by stable typing speed and stable
      typing ratio from long to short intervals. For an unstable Morse code typing
      pattern, the auto-recognition algorithms in the literature are not good enough
      for applications. This paper adopted a neural network to recognize unstable Morse
      codes. From an experiment on a teenager with cerebral palsy, the neural network
      has an average recognition rate up to 93.2%. The recognition rate from an amputee
      aged 40, who used a prosthesis for typing, it is 97.2% on average. When we
      compare this to 99.2% for the recognition rate from a skilled expert, the result
      is quite promising. The neural network has successfully overcome the difficulty
      of analysing a severely unstable Morse code time series. Since the human typing
      speed is quite slow in comparison to signal processing by the computer, it also
      makes it possible to use a neural network for real-time signal recognition.

PMID- 11530827
TI  - Commentary 'Effects of asymmetric branch flow rates on aerosol deposition in
      bifurcating airways', by Z. Zhang, C. Kleinstreuer and C. S. Kim.

PMID- 11530828
TI  - Three-dimensional static parametric modelling of phasic colonic contractions for
      the purpose of microprocessor-controlled functional stimulation.
AB  - The study aimed at creating an integrated electromechanical model of invoked
      phasic contractions in canine colon during direct high frequency voltage
      stimulation. The model utilized data obtained from two large anaesthetized dogs
      that underwent laparotomy and serosal implantation of two circumferential
      electrode pairs into a distal segment of the left colon. The strength
      distribution of the stimulating electric field was analysed over a cylindrical
      mesh-surface grid modelling the interrogated colonic segment. Recordings of the
      stimulating current were utilized to model smooth muscle depolarization using
      linearized macroscopic tissue conductivity. The invoked contractile stress was
      related to the stimulating electric field strength using an exponential sigmoid
      function. Artificially produced occlusion of the lumen was derived for a pair of
      5mm electrodes positioned on a cylindrical mesh-surface of 2 cm diameter and 15
      cm length. The model simulated contractions invoked by stimuli of different
      amplitude (up to 12 V) with 98.6% accuracy of approximation. Macroscopic tissue
      conductivity was modelled as a combination of two first-order exponential terms
      involving a 3ms time constant. Real-time simulation of the current drawn by the
      smooth muscle during 10 V/50Hz bipolar voltage stimulation was performed. The
      integrated electromechanical model facilitates the quantification of
      microprocessor-controlled phasic colonic contractions.

PMID- 11530829
TI  - An accurate programmable ECG simulator.
AB  - This article reports the design and development of an ECG simulator intended for
      use in the testing, calibration and maintenance of electrocardiographic
      equipment. It generates a lead II signal having a profile that varies with heart
      rate in a manner which reflects the true in vivo variation. Facilities are
      provided for user adjustment of heart rate, signal amplitude, QRS complex up
      slope, and the relative amplitudes of the P-wave and T-wave. The heart rate can
      be set within the range 30-200 beats min(-1) in steps of 1 beat min(-1). The
      amplitude of the QR5 complex can be adjusted from 0.1-20 mV in 0.1 mV steps,
      while its up-slope can be set between 10 and 50 ms with a 1 ms resolution. The
      amplitude of the P-wave can be varied from 5-40% and that of the T-wave from 10
      80% of the amplitude of the QRS complex with a 1% resolution.

PMID- 11530830
TI  - The effects of alcohol and diallyl sulphide on CYP2E1 activity in humans: a
      phenotyping study using chlorzoxazone.
AB  - The effects of acute administration of dietary levels of ethanol and the garlic
      oil extract, diallyl sulphide (DAS), on cytochrome P450 2E1 (CYP2E1) activity in
      volunteers were studied using the selective probe substrate, chlorzoxazone (CZX).
      The ratio of the CZX metabolite 6- hydroxychlorzoxazone (6-OHCZX) to CZX was
      taken to indicate CYP2E1 activity. The mean differences between the baseline and
      DAS-treated (0.2 mg/kg) CYP2E1 activities were significantly different (two
      tailed p value = 0.0242, n = 8). Likewise, the mean differences between the
      baseline and ethanol-treated (0.8 g/kg) CYP2E1 activities were also significantly
      different (two-tailed p value = 0.0005, n = 7). The reduction in in vivo CYP2E1
      activity by DAS is consistent with reported inhibition observed in vitro. The
      marked reduction in CYP2E1 activity following acute ingestion of ethanol is
      consistent with a competitive inhibition mechanism of CZX metabolism. The
      inhibitory effect of DAS maybe additive with daily consumption of Allium
      vegetables in particular. This may explain the lower 6-OHCZX/CZX metabolic ratios
      measured in various European and Mexican cohorts and is consistent with the lower
      incidence of stomach, liver and colon cancers observed in southern Europeans.

PMID- 11530831
TI  - Immunotoxicological investigations on rats treated subacutely with dimethoate,
      As3+ and Hg2+ in combination.
AB  - Effects of combined exposure with dimethoate (DM), HgCl2 (Hg), and NaAsO2 (As)
      were investigated following a 28 - day oral exposure in male Wistar rats. In
      preliminary experiments, the LOEL (Lowest Observed Effect Level) and NOEL (Non
      Observed Effect Level) doses of the substances were determined using the same
      experimental system [determination of body weight gain, organ weights of brain,
      thymus, heart, lung, kidneys, adrenals, spleen, testicles, popliteal lymph node,
      white blood cell (WBC) and red blood cell (RBC) count, haematocrit (Ht), mean
      cell volume (MCV) of RBCs, cell content of the femoral bone marrow, IgM-plaque
      forming cell (PFC) content of the spleen, delayed type hypersensitivity (DTH)
      reaction] and animal strain. In the combination studies, LOEL dose of DM (28.2
      mg/kg) was combined with NOEL doses of the heavy metals ( HgCl2 = 0.40 mg/kg,
      NaAsO2 = 3.33 mg/kg), and vice versa (DM = 7.04 mg/kg, HgCl2 = 3.20 mg/kg, NaAsO2
      = 13.3 mg/kg). In the DM-Hg combinations, significant alterations were found
      versus the corresponding high- dose internal control in the body weight gain,
      relative liver and kidney weights, and in the PFC response. When DM was combined
      with As, interactions were indicated by changes of relative liver weight, MCV
      value, and the PFC content of the spleen. These results support the theory that
      the interactions between pesticides and heavy metals may modify the toxic effects
      of the single substances, and may also change the functional detection limits of
      the exposure. The changes in the functional detection limits, if they occur, can
      lead to false-positive and false-negative results in human epidemiological
      studies.

PMID- 11530832
TI  - Effects of water-soluble antioxidant from spinach, NAO, on doxorubicin-induced
      heart injury.
AB  - Doxorubicin (DOX) produces clinically restorative responses in numerous human
      cancers, but its cardiotoxicity has limited its usefulness. Because reactive
      oxygen species may affect DOX-induced antitumor activity and cardiotoxicity, we
      evaluated the prophylactic effect of spinach natural antioxidant (NAO) on DOX
      induced cardiotoxicity and oxidative stress in female Balb/c mice using
      histological, electron microscopical and biochemical parameters. Mice were
      treated with NAO for 7 days prior to and/or for 6 days after DOX administration.
      Pretreatment with NAO (cumulative dose: 130 mg/kg) did not hinder the
      effectiveness of DOX. Light and electron microscopy of DOX-treated heart revealed
      myocardial degeneration. When administered combined before and after DOX, NAO
      conferred the most significant cardiac protection. The effects of NAO on the
      lipid peroxidation product, malondialdehyde, and on H2O2/ hydroperoxides were
      examined on day 6 following DOX administration; levels of both were elevated in
      DOX-treated mice, compared to control. Pretreatment with NAO prevented these
      changes. Pretreatment with NAO before DOX administration decreased catalase and
      increased superoxide dismutase activities compared to the DOX group. Our results
      suggest usage of NAO in combination with DOX as a prophylactic strategy to
      protect heart muscle from DOX-induced cellular damage.

PMID- 11530833
TI  - Metal-induced hormesis requires cPKC-dependent glucose transport and lowered
      respiration.
AB  - Previously, cytotoxicity studies using an 3-(4,5 dimethylthiazol-2-yl)-2,5
      diphenyl tetrazolium bromide (MTT)-based in vitro toxicity assay found that low
      concentrations of mercuric, cadmium and cupric chloride (0.7, 1 and 3 pM,
      respectively) induced hormesis in McCoy cells after 24 h exposure. An
      investigation of the biochemical events required for the induction of this
      phenomenon revealed that hormesis was dependent on two simultaneous but
      independent events, namely, an 11-15% conventional protein kinase C (cPKC)
      dependent increase in glucose uptake and a protein synthesis-dependent 19-23%
      drop in mitochondrial respiration. The inhibition of either event was sufficient
      to abolish hormesis for all three metal toxicants. Furthermore, an investigation
      of the energy status of cells prior to and during hormesis revealed an
      oscillating level of ATP production found to be in phase with mitochondrial
      respiration, independent of cPKC-activated glucose transport and found to
      coincide with a 16-20% drop in AMP-activated protein kinase activity. These
      findings suggest that hormesis is not a form of energy compensation but is most
      likely a reductive burst where an increase in glucose uptake together with a
      simultaneous reduction in oxygen consumption results in a significant increase in
      reduction equivalents, which may then be utilized by cells to counteract the
      effects of oxidative stress induced by heavy metal toxicants.

PMID- 11530834
TI  - Effects of the antianginal drug fendiline on Ca2+ movement in hepatoma cells.
AB  - This study investigated the effect of the anti-anginal drug, fendiline, on
      intracellular free Ca2+ levels ([Ca2+]i) in HA/ 22 human hepatoma cells by using
      fura-2 as a fluorescent Ca2+ dye. Fendiline (1-100 microM) increased [Ca2+]i with
      an EC50 of 25 microM. Removal of extracellular Ca2+ reduced the [Ca2+]i signals
      by 51 +/- 5%. Fendiline (10 microM)-induced Ca2+ release was abolished by
      pretreatment with 1 microM thapsigargin (an endoplasmic reticulum Ca2+ pump
      inhibitor). Inhibition of phospholipase C with 2 microM 1-(6-((17beta-3
      methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione (U73122) did
      not alter 10 microM fendiline-induced Ca2+ release. Several other calmodulin
      antagonists, such as phenoxybenzamine (100-200 microM), trifluoperazine (5-50
      microM), and fluphenazine-N-chloroethane (2-100 microM), had no effect on
      [Ca2+]i. Together, it was found that fendiline increased [Ca2+]i in human
      hepatoma cells by discharging Ca2+ from the endoplasmic reticulum in an inositol
      1,4,5-trisphosphate-independent manner and by inducing Ca2+ entry. This effect of
      fendiline does not appear to be via antagonism of calmodulin.

PMID- 11530835
TI  - Deferoxamine toxicity in hepatoma and primary rat cortical brain cultures.
AB  - Deferoxamine is commonly used for treatment of iron intoxication. Because the
      usual dose is unable to chelate sufficient iron before severe injury occurs,
      "high-dose" deferoxamine treatment has been proposed. However, several authors
      have reported severe toxicity after deferoxamine therapy. Although the
      hemodynamic effects are well described, the cellular toxicity of deferoxamine is
      unknown. Accordingly, we investigated the cellular toxicity of deferoxamine using
      in vitro techniques in two cell lines. Brain cells were harvested from fetal rats
      and cultured for 14-21 days before deferoxamine exposure. Using similar
      techniques, rat hepatoma cells were grown until confluent. Deferoxamine was added
      to the cultures to achieve final concentrations of 200-800 microg/ml,
      corresponding to in vivo infusion rates of 15-60 mg/kg/h. Deferoxamine was
      removed after 3 or 6 days by changing the medium. Subtoxic FeCl3 (500 mg/dl) was
      concurrently added to identical cultures to determine if deferoxamine potentiated
      iron toxicity. Cell viability was measured by a colorimetric assay. The addition
      of deferoxamine (0.2, 0.4, 0.8 mg/ml) significantly decreased cell viability in
      both cell groups. The effect of deferoxamine on primary cortical brain cultures
      was similar for the three concentrations used, and was similar when examined
      either 72 h or 6 days later. In contrast, hepatoma cell cultures evidenced a dose
      dependent cell loss that increased with the length of exposure. The addition
      ofsubtoxic amounts of FeCl3 (500 microg/dl) in the presence of deferoxamine was
      protective in all cultures, and abolished deferoxamine-induced cell loss.
      Interestingly, the addition of serum albumin significantly reduced the amount of
      iron present in cells, suggesting its potential use to treat iron toxicity. These
      results suggest that deferoxamine, in the absence of iron, is toxic to cortical
      brain and hepatoma cells in vitro.

PMID- 11530836
TI  - Effect of peroxynitrite on glutaredoxin.
AB  - Glutaredoxin is an important enzyme in thiol homeostasis. As a thioltransferase,
      it reduces oxidized thiols. It also has dehydroascorbate reductase (DHAR)
      activity to reduce dehydroascorbate (DHA) to ascorbic acid. Peroxynitrite (ONOO-)
      is one of the most active elements of oxidative stress that can be formed
      wherever nitric oxide and superoxide are produced simultaneously. ONOO- is known
      to react with free thiols easily. To observe the effect of ONOO on glutaredoxin,
      rat liver cytosolic fractions were incubated with 0-250 microM ONOO-.
      Thioltransferase activity was found to be decreased as ONOO concentration
      increased. The inhibition was not reversible with dithiothreitol (DTT). In
      cytosol besides glutaredoxin, another enzyme with DHAR activity is also present.
      In our study, the cytosolic DHAR activity which consisted both enzymes, was also
      inhibited by ONOO-, but DTT was able to return the activity almost completely.

PMID- 11530837
TI  - Parasuicide by self-injection of an organophosphate insecticide.
AB  - Parasuicide by ingestion of organophosphate (OP) insecticides is common in Sri
      Lanka, but the use of the parateral route to self administer the poison is
      extremely rare. We report a patient who deliberately injected herself
      intramuscularly with an OP compound with suicidal intent. The clinical
      manifestations of OP poisoning were unpredictable and posed a therapeutic
      problem.

PMID- 11530838
TI  - Medial temporal and prefrontal contributions to working memory tasks with novel
      and familiar stimuli.
AB  - Lesions of parahippocampal structures impair performance of delayed matching
      tasks in nonhuman primates, suggesting a role for these structures in the
      maintenance of items in working memory and short-term stimulus matching. However,
      most human functional imaging studies have not shown medial temporal activation
      during working memory tasks and have primarily focused on functional magnetic
      resonance imaging (fMRI) signal intensity changes in the prefrontal and posterior
      parietal cortex. The goal of this study was to test the hypothesis that the
      difference between the human and nonhuman primate data results from the use of
      highly familiar stimuli in human working memory studies and trial-unique stimuli
      in nonhuman primate studies. We used fMRI to examine prefrontal and temporal lobe
      activation during performance of a working memory (two-back) task, using blocks
      of novel and highly familiar complex pictures. Performance of the working memory
      task with novel complex pictures resulted in greater signal change within medial
      temporal lobe structures than performance of the task with familiar complex
      pictures. In contrast, the working memory task with highly familiar stimuli
      resulted in greater prefrontal activation. These results are consistent without
      hypothesis that the medial temporal lobe is recruited for the short-term
      maintenance of information that has no prior representation in the brain, whereas
      the prefrontal cortex is important for monitoring familiar stimuli that have a
      high degree of interference. A second set of tasks examined stimulus matching.
      Subjects performed a target-matching task, during which they identified a single
      target presented in blocks of novel or familiar stimuli. The results provide
      evidence of hippocampal and parahippocampal recruitment in the target-matching
      task with familiar stimuli. These results are consistent with prior animal
      studies and suggest that prefrontal regions may be important for the monitoring
      and matching of familiar stimuli which have a high potential for interference,
      whereas medial temporal regions may become proportionally more important for
      matching and maintenance of novel stimuli.

PMID- 11530839
TI  - Bilateral medial temporal lobe damage does not affect lexical or grammatical
      processing: evidence from amnesic patient H.M.
AB  - In the most extensive investigation to date of language in global amnesia, we
      acquired data from experimental measures and examined longitudinal data from
      standardized tests, to determine whether language function was preserved in the
      amnesic patient H.M. The experimental measures indicated that H.M. performed
      normally on tests of lexical memory and grammatical function, relative to age-
      and education-matched control participants. Longitudinal data from four Wechsler
      subtests (Information, Comprehension, Similarities, and Vocabulary), that H.M.
      had taken 20 times between 1953 (preoperatively) and 2000, indicated consistent
      performance across time, and provided no evidence of a lexical memory decrement.
      We conclude that medial temporal lobe structures are not critical for retention
      and use of already acquired lexical information or for grammatical processing.
      They are, however, required for acquisition of lexical information, as evidenced
      in previous studies revealing H.M.'s profound impairment at learning new words.

PMID- 11530840
TI  - MRI-Based evaluation of locus and extent of neurotoxic lesions in monkeys.
AB  - To minimize the variability in the extent of lesions made by injections of the
      excitotoxin ibotenic acid in rhesus monkeys, we developed and validated an MRI
      based method to determine the efficacy of the injections soon after surgery. T2
      weighted MR images were obtained 6-11 days after surgery from 17 brain
      hemispheres of monkeys that had received bilateral lesions of either the
      hippocampal formation (HF), perirhinal cortex, or parahippocampal cortex. The
      extent of lesion estimated from the hypersignal that appeared in and outside of
      the targeted area on these MR images was compared with the extent of damage
      assessed histologically after survival periods ranging from 120-370 days. Highly
      significant correlations (r values between 0.85-0.99) were found between these
      two measures for several regions in the medial temporal lobe. Based on this
      finding, lack of hypersignal in the targeted area of some Ss was followed by
      successful reinjection of the neurotoxin to create more complete cell loss prior
      to the postoperative phase of the study. We also assessed the relationship
      between a postoperative reduction in HF volume, measured from T1-weighted MR
      images, and the extent of damage determined histologically in 14 hemispheres of
      monkeys with bilateral excitotoxic HF lesions. The HF volume decreases sharply
      after surgery until 40-50 days postoperatively, after which there is only a minor
      further decrease. Based on this finding, we obtained T1-weighted MR images at
      least 44 days but in most cases close to 1 year after surgery. A highly
      significant positive correlation (r = 0.95, P < 0.001) was found between neuronal
      damage and volume reduction, with nearly complete neuronal damage (96-99%)
      corresponding to a volume reduction of 68-79%. These MRI-based methods thus
      provide an accurate in vivo evaluation of the locus and extent of neurotoxic
      lesions. Application of these methods can ensure that each animal in the
      experiment is used effectively.

PMID- 11530841
TI  - Cholinergic modulation of pavlovian fear conditioning: effects of
      intrahippocampal scopolamine infusion.
AB  - Cholinergic neurotransmission has been implicated in the acquisition of a variety
      of tasks, including Pavlovian fear conditioning. To more precisely define the
      role of cholinergic modulation in this process, the effect of site-specific
      cholinergic antagonism was assessed. Male Long-Evans rats were implanted with
      chronic, bilateral cannulae aimed at the dorsal hippocampus. Infusions of
      scopolamine hydrobromide (50 microg bilaterally) or phosphate-buffered saline
      (PBS) were made immediately prior to a signaled Pavlovian fear conditioning
      procedure. On consecutive days following training, all rats were given
      independent tests assessing freezing to both the training context and the tone
      conditional stimulus (CS). Relative to PBS infused controls, rats that received
      intrahippocampal infusions of scopolamine showed a significant attenuation of
      contextual freezing but comparable levels of freezing to the tone CS. Neither
      shock sensitivity nor general activity levels differed between rats infused with
      scopolamine or PBS. These findings suggest that fear conditioning to context, but
      not discrete CS, requires intact cholinergic neurotransmission in the
      hippocampus.

PMID- 11530842
TI  - Evidence for a relationship between place-cell spatial firing and spatial memory
      performance.
AB  - The rat hippocampus contains place cells whose firing is location-specific.
      Although many properties of place cells have been uncovered, little is known
      about their actual contribution to the animal's spatial performance. In this
      study, we addressed this issue by recording place cells while rats solved a
      continuous spatial alternation task in which they had to alternate between the
      two arms of a Y-maze to get a food reward in the third (goal) arm. By
      manipulating the information available to the animals, we induced the cells to
      establish their fields in locations that were out of register relative to their
      standard position, thus making them inconsistent with the learned spatial task.
      When this happened, the rats' performance in the alternation task was markedly
      decreased. In addition, the nature of the behavioral errors during inconsistent
      field placements also changed dramatically in a way that was highly indicative of
      the rats' spatial disorientation. These results suggest that there is a
      functional relationship between the spatial firing patterns of place cells and
      the spatial behavior of the rat, thus strengthening the idea that these cells are
      part of a navigational system.

PMID- 11530843
TI  - Synaptic plasticity in the hippocampus of awake C57BL/6 and DBA/2 mice:
      interstrain differences and parallels with behavior.
AB  - C57BL/6 mice consistently outperform DBA/2 mice in a range of hippocampal
      dependent spatial learning behaviors. We recorded evoked responses from the
      dentate gyrus of awake, freely-moving mice and measured synaptic plasticity (LTP)
      and performance in a hippocampal-dependent task in individual animals from these
      two inbred strains. Spatial alternation tasks confirmed the behavioral divergence
      between the two strains, with C57BL/6 mice demonstrating more robust alternation
      than DBA/2 mice. Recording changes in field potentials in the dentate gyrus
      following three different high-frequency stimulation paradigms in the same groups
      of animals revealed differences in neural plasticity: both strains were able to
      support long-term potentiation (LTP) at perforant path synapses, but brief high
      frequency stimulation induced larger and longer potentiation of the population
      spike in C57BL/6 than in DBA/2 mice. This greater propensity for population-spike
      potentiation in the strain that performed better in a hippocampal-dependent task
      is in accord with the different neurochemical profiles of C57BL/6 and DBA/2 mice.

PMID- 11530844
TI  - Entorhinal cortex of the mouse: cytoarchitectonical organization.
AB  - The present study describes the cytoarchitectonical and chemoarchitectonical
      organization of the entorhinal cortex of the mouse (C57BL/6J strain). The
      entorhinal cortex is medially bordered by the parasubiculum, and laterally by the
      perirhinal cortex; rostrally and medially it is bordered by the piriform cortex,
      whereas caudally and dorsally it is bordered by the postrhinal cortex. The
      entorhinal cortex is divided into two main areas, i.e., the lateral entorhinal
      area (LEA) and the medial entorhinal area (MEA). Both entorhinal areas are
      further divided into subfields, i.e., LEA is divided into DLE (dorsolateral
      entorhinal field), DIE (dorsal intermediate entorhinal field), and VIE (ventral
      intermediate entorhinal field), whereas MEA is divided into CE (caudal entorhinal
      field) and ME (medial entorhinal field). Cytoarchitectonically, the main
      difference between LEA and MEA is displayed by layer II neurons: while these are
      in a dense layer in LEA, they are more dispersed in MEA. Further, in LEA there is
      a relatively cell-free zone between layers II and III; this zone is not present
      in MEA. Histochemically, in acetylcholinesterase (AChE)-stained material, MEA is
      characterized by darker-stained bands in the superficial layer (i.e., layer I)
      and in the lamina dissecans, in contrast to LEA, which is more evenly stained for
      AChE. Further, both the border with the perirhinal cortex and the border with the
      parasubiculum are characterized by dark-stained bands of AChE. The border between
      the entorhinal cortex and perirhinal cortex is also easily distinguished in
      parvalbumin-stained material; while the entorhinal cortex is darkly stained, the
      perirhinal cortex is lightly stained. In contrast, in sections stained for
      calretinin, the entorhinal cortex is more lightly stained than the parasubiculum,
      which has a darkly stained superficial layer, and a densely stained group of
      neurons in layer III.

PMID- 11530845
TI  - Revisiting the role of the hippocampal mossy fiber synapse.
AB  - The mossy fiber pathway has long been considered to provide the major source of
      excitatory input to pyramidal cells of hippocampal area CA3. In this review we
      describe anatomical and physiological properties of this pathway that challenge
      this view. We argue that the mossy fiber pathway does not provide the main input
      to CA3 pyramidal cells, and that the short-term plasticity and amplitude variance
      of mossy fiber synapses may be more important features than their long-term
      plasticity or absolute input strength.

PMID- 11530846
TI  - Somatostatin-immunoreactive interneurons contribute to lateral inhibitory
      circuits in the dentate gyrus of control and epileptic rats.
AB  - Lateral inhibition, a feature of neuronal circuitry that enhances signaling
      specificity, has been demonstrated in the rat dentate gyrus. However, neither the
      underlying neuronal circuits, nor the ways in which these circuits are altered in
      temporal lobe epilepsy, are completely understood. This study examines the
      potential contribution of one class of inhibitory interneurons to lateral
      inhibitory circuits in the dentate gyrus of both control and epileptic rats. The
      retrograde tracer wheat germ ag-glutinin-apo-horse radish peroxidase-gold (WGA
      apo-HRP-gold) was injected into the septal dentate gyrus. Neurons double-labeled
      for glutamic acid decarboxylase (GAD) and the retrograde tracer are concentrated
      in the hilus and may contribute to lateral inhibition. Neurons double-labeled for
      somatostatin and the retrograde tracer account for at least 28% of GAD-positive
      neurons with axon projections appropriate for generating lateral inhibition in
      control rats. Despite an overall loss of somatostatin-expressing cells in
      epileptic animals, the number of somatostatin-positive interneurons with axon
      projections appropriate for generating lateral inhibition is similar to that seen
      in controls. These findings suggest that somatostatinergic interneurons
      participate in lateral inhibitory circuits in the dentate gyrus of both control
      and epileptic rats, and that surviving somatostatinergic interneurons might
      sprout new axon collaterals in epileptic animals.

PMID- 11530847
TI  - Increased extracellular release of hippocampal NE is associated with tetanization
      of the medial perforant pathway in the freely moving adult male rat.
AB  - The induction of long-term potentiation (LTP) within the dentate gyrus of the
      hippocampal formation is modulated by many afferent influences from a number of
      subcortical structures known to be intimately involved in hippocampal-dependent
      learning and memory. It has been demonstrated in slice and anesthetized
      preparations that norepinephrine (NE) is one of these major neuromodulators
      involved in the induction of LTP. However, the majority of these studies have not
      been conducted in the freely moving animal. Recently, we developed surgical
      procedures and instrumentation techniques to simultaneously record
      electrophysiological and neurochemical data from the hippocampal formation. The
      present study uses these techniques to examine the underlying neurochemical
      changes in the hippocampus associated with the induction of hippocampal dentate
      LTP in the freely moving adult rat. These findings establish baseline levels of
      NE that can be used to evaluate the impact of various tetanization paradigms as
      well as the effect of a variety of insults on hippocampal plasticity.

PMID- 11530848
TI  - Expression profile of 30,000 genes in rat hippocampus using SAGE.
AB  - Using the serial analysis of gene expression (SAGE) method, we generated a gene
      expression profile of the rat hippocampus. A total of 76,790 SAGE tags was
      analyzed, allowing identification of 28,748 different tag species, each
      representing a unique mRNA transcript. The tags were divided into different
      abundancy classes, ranging from tags that were detected over 500 times to tags
      encountered only once in the 76,790 tags analyzed. The mRNA species detected more
      than 50 times represented 0.3% of the total number of unique tags while
      accounting for 22% of the total hippocampal mRNA mass. The majority of tags were
      encountered 5 times or less. The genes expressed at the highest levels were of
      mitochondrial origin, consistent with a high requirement for energy in neuronal
      tissue. At a lower level of expression, several neuron-specific transcripts were
      encountered, encoding various neurotransmitter receptors, transporters, and
      enzymes involved in neurotransmitter synthesis and turnover, ion channels and
      pumps, and synaptic components. Comparison of relative expression levels
      demonstrated that glutamate receptors are the most frequent neurotransmitter
      receptors expressed in the hippocampus, consistent with the important role of
      glutamatergic neurotransmission in the hippocampus, while GABA receptors were
      present at approximately 10-fold lower levels. Several kinases were present
      including CaMKII, which was expressed at high levels, consistent with its being
      the most abundant protein in the spines of hippocampal pyramidal cells. This is
      the first extensive inventory of gene expression in the hippocampus and serves as
      a reference for future studies aimed at elucidating hippocampal transcriptional
      responses under various conditions.

PMID- 11530849
TI  - Prevention of isolation-induced hypertension by intrahippocampal administration
      of a nonpeptide kappa-opioid receptor agonist.
AB  - Previous research in this laboratory showed that hypertension in the spontaneous
      hypertensive rat (SHR) appears to correlate to insufficient production of
      hippocampal dynorphins, and that blood pressure could be reduced by
      intrahippocampal administration of dynorphins and nonpeptide kappa agonists. The
      purpose of the present study was to investigate whether kappa agonists could
      prevent the development of hypertension in a different hypertensive model, i.e.,
      the isolated male rat model of hypertension (IHR). Isolation of young male rats
      for 5-7 days in standard rat cages caused an increase in systolic blood pressure
      from a mean of 132 to 184 mmHg. The blood pressures of rats grouped 3 per cage
      remained stable. Rats received the nonpeptide kappa agonist U62, 066E,
      (Spiradoline, Upjohn), 10 nmoles/0.2 microl or drug vehicle bilaterally into the
      the hippocampus for 3 days prior to and during isolation or grouping. Animals
      treated with U62, 066E did not develop hypertension as compared to isolated
      animals treated with vehicle. The isolation procedure used in these studies
      appears to induce anxietal stress, as indicated by reduced time spent by the rats
      in the open arms of the elevated-plus maze. This time is increased by U62, 066E,
      suggesting that the drug possesses anxiolytic properties and may reduce
      hypertension in part, by blocking an anxiety/stress component. These data
      strengthen our previous findings that opioids in the hippocampus may be important
      in restraining increased blood pressure provoked by environmental stimuli such as
      isolation.

PMID- 11530850
TI  - Alterations of hippocampal GAbaergic system contribute to development of
      spontaneous recurrent seizures in the rat lithium-pilocarpine model of temporal
      lobe epilepsy.
AB  - Reorganization of excitatory and inhibitory circuits in the hippocampal formation
      following seizure-induced neuronal loss has been proposed to underlie the
      development of chronic seizures in temporal lobe epilepsy (TLE). Here, we
      investigated whether specific morphological alterations of the GABAergic system
      can be related to the onset of spontaneous recurrent seizures (SRS) in the rat
      lithium-pilocarpine model of TLE. Immunohistochemical staining for markers of
      interneurons and their projections, including parvalbumin (PV), calretinin (CR),
      calbindin (CB), glutamic acid decarboxylase (GAD), and type 1 GABA transporter
      (GAT1), was performed in brain sections of rats treated with lithium-pilocarpine
      and sacrificed after 24 h, during the silent phase (6 and 12 days), or after the
      onset of SRS (10-18 days after treatment). Semiquantitative analysis revealed a
      selective loss of interneurons in the stratum oriens of CA1, associated with a
      reduction of GAT1 staining in the stratum radiatum and stratum oriens. In
      contrast, interneurons in CA3 were largely preserved, although GAT1 staining was
      also reduced. These changes occurred within 6 days after treatment and were
      therefore insufficient to cause SRS. In the dentate gyrus, extensive cell loss
      occurred in the hilus. The pericellular innervation of granule cells by PV
      positive axons was markedly reduced, although the loss of PV-interneurons was
      only partial. Most strikingly, the density of GABAergic axons, positive for both
      GAD and GAT1, was dramatically increased in the inner molecular layer. This
      change emerged during the silent period, but was most marked in animals with SRS.
      Finally, supernumerary CB-positive neurons were detected in the hilus,
      selectively in rats with SRS. These findings suggest that alterations of
      GABAergic circuits occur early after lithium-pilocarpine-induced status
      epilepticus and contribute to epileptogenesis. In particular, the reorganization
      of GABAergic axons in the dentate gyrus might contribute to synchronize
      hyperexcitability induced by the interneuron loss during the silent period,
      leading to the onset of chronic seizures.

PMID- 11530851
TI  - Acute stress and dexamethasone rapidly increase hippocampal somatostatin
      synthesis and release from the dentate gyrus hilus.
AB  - Somatostatin is a neuropeptide whose facilitatory action in the generation of
      long-term potentiation (LTP) in the hippocampal dentate gyrus has been associated
      with memory processes. Since stress and memory seem to share some neural
      pathways, we studied somatostatin release from dentate gyrus hilar cells of the
      hippocampus in unanesthetized free-moving rats subjected to stress or
      dexamethasone treatments. In parallel, the number of dentate gyrus hilar cells
      expressing somatostatin mRNA was quantified by nonradioactive in situ
      hybridization in these two experimental conditions. Rats were stereotaxically
      implanted with a push-pull cannula in the dentate gyrus hilar region. Animals
      were perfused 1 week later in basal or stress (30 min immobilization stress)
      conditions. The other group was intraperitoneally injected with the synthetic
      glucocorticoid dexamethasone (3 mg/kg b.w.). Samples were collected every 15 min
      for somatostatin radioimmunoassay. In parallel, in other groups of animals
      undergoing the same treatments, brains were removed for in situ hybridization
      studies with an oligonucleotide labeled with digoxigenin that recognizes
      somatostatin-14. The results showed that stress induced a significant increase in
      somatostatin release from dentate gyrus hilar cells 30-45 min after
      immobilization stress application. Dexamethasone-injected animals exhibited a
      similar response 45 min after drug administration. In situ hybridization analysis
      revealed that the two treatments significantly increased the number of cells
      expressing somatostatin mRNA in the hilar region. In conclusion, somatostatin
      interneurons of the hippocampal hilar region appear to be a novel stress stimulus
      target. Their rapid reactivity, expressed as modifications of both somatostatin
      release and number of cells expressing somatostatin mRNA, provides an interesting
      model of neuronal plasticity.

PMID- 11530852
TI  - Mitochondrial DNA reveal that domestic goat (Capra hircus) are genetically
      affected by two subspecies of bezoar (Capra aegagurus).
AB  - This article describes the complete sequences of the mitochondrial DNA
      displacement loop (D-loop) region and cytochrome b gene from domestic goats in
      Laos (Laos native) and wild goat "markhor" (C. falconeri). The wild goat "bezoar"
      (Capra aegagrus) has been considered to be the strongest candidate for the
      ancestor of the domestic goats (C. hircus); however, there is not sufficient
      molecular data to verify the hypothesis at present. In phylogenetic analyses, two
      wild goats, the markhor and the ibex (C. ibex), appeared as an outgroup, while
      the bezoar was located in a cluster of domestic goats. Mitochondrial haplotypes
      of Laos natives revealed two distinct major clusters: one was the same as the
      bezoar, the second, unique to Laos natives. The topology and calibrated levels of
      sequence divergence suggests that these clusters might represent at least two
      different subspecies of ancestral bezoars.

PMID- 11530853
TI  - Genetic divergence and phylogenetic relationships in grey mullets (Teleostei:
      Mugilidae) using allozyme data.
AB  - Genetic divergence and phylogenetic relationships among five species of the
      Mugilidae family (Liza saliens, Liza aurata, Liza ramada, Chelon labrosus, and
      Mugil cephalus) were investigated, in the present study, on samples taken from
      Messolongi lagoon in Greece, using allozyme electrophoresis. Ten enzymic systems
      corresponding to 22 genetic loci were assayed, among which, four were found to be
      polymorphic in Liza saliens, Liza aurata, and Chelon labrosus, seven in Liza
      ramada, while only two were polymorphic in Mugil cephalus. Several loci showed
      different electrophoretic patterns among the species and thus, they can be useful
      in species taxonomy as diagnostic markers, as well as for further evolutionary
      studies. It must be underlined that among them the aGPD-2* locus proved to be
      species-specific, while the other ones can be also used in various combinations
      for the same purpose. The observed heterozygosity wasfound to range from 0.020 to
      0.051. Allele frequencies of all loci were used to estimate Nei's (1972) genetic
      distance, which was found to range between 0.249 and 1.171 among the five species
      studied. UPGMA and NJ trees, obtained by genetic distance matrix methods, as well
      as, a tree based on the discrete character parsimony analysis were found to
      exhibit the same topology. Our result show that the three species of the genus
      Liza are clustered together, Chelon labrosus being closer to the previous clade,
      while Mugil cephalus being more distinct.

PMID- 11530854
TI  - Genetic analysis and mapping of biochemical markers in an F2 intercross of two
      inbred strains of the rabbit (Oryctolagus cuniculus).
AB  - A total of 40 biochemical and four immunological markers found to be polymorphic
      in the rabbit in previous studies were screened in the AX/JU and IIIVO/JU inbred
      strains. Although the strains are considered unrelated, only eight (biochemical)
      markers werefound to be polymorphic between the two strains. These eight markers
      were analyzed in an F2 intercross population. Linkage was found for Est-5 and C
      on chromosome 1 and for Es-1, Est-2, Est-4, Est-6 and HP on linkage group VI. Two
      polymorphic markers, Es-3 and Mhr-1 could not be linked to any of the other
      markers.

PMID- 11530855
TI  - Use of DNA markers in prediction of hybrid performance and heterosis for a three
      line hybrid system in rice.
AB  - Two Cytoplasmic Male Sterile lines were crossed with fourteen restorer lines of
      rice widely grown in the western regions of Maharashtra, India, to produce 28 F1
      hybrids which were evaluated for eight agronomically important traits,
      contributing to yield potential, in replicated field trials. The hybrid
      performance was recorded along with heterosis and heterobeltiosis. All the rice
      lines under investigation were subjected to marker-based variability analysis. An
      attempt was made to correlate genetic distance based on specific markers for each
      trait individually, as well as average genetic distance based on all specific
      markers, with hybrid performance and heterosis, by regression analysis. Specific
      markers could cluster the parental lines in different groups and showed
      significant correlation with hybrid performance. The data also supports the
      proposition that epistasis is the basis of heterosis. The analysis, however,
      revealed a lack of significant predictive values for field application.

PMID- 11530856
TI  - Phylogenetic relationships of the seven coat protein subunits of the coatomer
      complex, and comparative sequence analysis of murine xenin and proxenin.
AB  - The coatomer complex is involved in intracellular protein transport and comprises
      an assembly of seven polypeptide subunits designated alpha, beta, beta', gamma,
      delta, epsilon, and zeta COP. Rooted phylogenetic trees constructed from the full
      length cDNA and amino acid sequences of 49 COP entities in different eukaryotes
      from yeast to man generally revealed striking conservation of each subunit
      through evolution. Both nucleotide and protein trees displayed close
      relationships between alpha and beta' subunits, between beta and gamma subunits,
      and between delta and zeta subunits, implying evolution from common ancestors as
      well as functional similarity. Interestingly, although 6 out of 7 epsilon-COP
      genes appeared to be grouped and related to the beta-COP genes, 4 out of 7
      epsilon

PMID- 11530857
TI  - Genetic diversity among different clones of the gynogenetic silver crucian carp,
      Carassius auratus gibelio, revealed by transferrin and isozyme markers.
AB  - Genetic diversity among four clones (A, D, E, F) of gynogenetic silver crucian
      carp was studied using transferrin and isozymes in the blood as markers. Of the
      five proteins investigated, three (transferrin, esterase and superoxide
      dismutase) indicated polymorphism and eight polymorphic loci were detected. These
      loci were probably encoded by codominant alleles and their inheritance patterns
      were analyzed. Intraclonal homogeneity and interclonal heterogeneity were
      observed in these clones, which allowed us to infer the clonal nature and
      evolutionary relationship between them. Clonal diversity in this population of
      silver crucian carp in China was also compared with data reported from
      gynogenetic crucian carp in Germany.

PMID- 11530858
TI  - Calcium metabolism in pregnancy: disturbed calcium homeostasis in diabetic
      pregnancy and preeclampsia.

PMID- 11530859
TI  - Maternal/paternal sharing of DQ-Alpha type II histocompatibility antigens not
      associated with pregnancy outcome following in vitro fertilization (IVF)-embryo
      transfer (ET).
AB  - PURPOSE: To determine if maternal/paternal sharing of DQ alpha major
      histocompatibility (MHC) type II antigens is associated with reduced pregnancy
      and implantation rates following in vitro fertilization-embryo transfer (IVF-ET).
      METHODS: Prospective study with type II MHC DQ alpha alleles detected by
      polymerase chain reaction (PCR) technology using Perkin Elmer Amyli-type HLA DQ
      alpha PCR amplification and typing kit. The tests were only performed on patients
      having their first IVF cycle. RESULTS: No difference was found in clinical
      pregnancy rates per transfer between those couples sharing DQ alpha I alleles and
      those who did not (43.7% vs 40%). There were no spontaneous abortions in the
      group sharing DQ alpha I alleles. CONCLUSION: Maternal/paternal sharing of DQ
      alpha I antigens does not reduce fecundity following IVF-ET.

PMID- 11530860
TI  - The immunolocalization of Bcl-2 in human term placenta.
AB  - PURPOSE: To study the immunolocalization of the Bcl-2 protein in formalin-fixed
      placental tissue collected from uncomplicated term pregnancies. METHODS: A total
      of 19 human term placentas of 38-41 weeks' gestation, 11 obtained from
      spontaneous deliveries and eight from elective caesarean sections prior to labour
      were included. Sections were incubated with an antibody to the Bcl-2 protein and
      light microscopy was used to evaluate Bcl-2 staining. RESULTS: The anti-apoptotic
      Bcl-2 protein was expressed diffusely throughout the cytoplasm of the
      syncytiotrophoblast with much less intensive staining in cytotrophoblast and
      mesenchymal cells. Bcl-2 expression was reduced or lost in areas of syncytial
      sprouts. No differences in Bcl-2 staining were observed between placentas
      obtained after spontaneous deliveries and those collected before the onset of
      labour after elective caesarean section. CONCLUSION: Expression of the anti
      apoptotic Bcl-2 protein in human term placenta does not seem to be influenced by
      parturition. Additionally, Bcl-2 expression might be an important factor in the
      regulation of apoptosis in the human trophoblast and thus in maintaining
      placental function during gestation.

PMID- 11530861
TI  - Cumulative pregnancy rates after four embryo transfers of either fresh or frozen
      embryos.
AB  - PURPOSE: To evaluate in the modern era of in vitro fertilization (IVF) cumulative
      probability of pregnancy for the first four embryo transfers (ET) irrespective of
      whether the embryos were fresh or frozen. METHODS: Retrospective review over a 2
      1/2 year period. Cumulative probability of pregnancy for four consecutive cycles
      of either fresh or frozen ETs divided into four age groups. RESULTS: The
      cumulative clinical and viable pregnancy rates after four ETs were 92% and 88%;
      87% and 82%; 83% and 69%; and 68% and 52% for age groups <30, 30-34, 35-39, and
      40-44. The cumulative rates decline with age. CONCLUSIONS: Pregnancy rates per
      transfer for the first four ETs regardless of age are similar even in IVF centers
      that emphasize frozen ETs.

PMID- 11530862
TI  - The immunophenotypic profile of hepatic hemopoiesis in fetuses with Down's
      syndrome during the second trimester of development.
AB  - The yolk sac and aorto-gonad-mesonephros region are well recognized as the
      principal sites of hematopoiesis in the developing embryo, and the liver is the
      principal site of hematopoiesis in the fetus. In the present study, we
      investigated the immunohistochemical expression of Glycophorin C (erythrocytes),
      Neutrophilic elastase (granulocytes), and CD34 (progenitor hematopoietic stem
      cells, progenitor stromal cells, and vascular endothelial cells) in hepatic
      parenchyma from fetuses with Down's syndrome (DS) (16th, 20th, and 24th week of
      gestational age), and correlated the findings with the equivalent of the hepatic
      parenchyma from fetuses after spontaneous abortion. Our results did not
      demonstrate a quantitative difference at the level of erythropoiesis in all three
      periods examined. In contrast, an important numerical difference was shown in the
      expression of CD34 positive cells in liver parenchyma from fetuses with DS, in
      comparison with those found in liver parenchyma from fetuses after spontaneous
      abortion (p < 0.02). Furthermore, a modest but significant difference was
      demonstrated at the level of granulopoiesis between the 20th and 24th week (p <
      0.01). Given that, the living newborns with Down's syndrome manifest diverse
      haematological abnormalities, including a transient leukemoid reaction that
      usually disappears after some weeks or months, a significantly increased number
      of CD34 positive and a less significantly increased number of neutrophilic
      elastase positive cells between the 20th and 24th gestational week could explain
      this phenomenon in combination with the respective results, if any, in the bone
      marrow. Regarding our finding of increased stromal CD34 positive cells in the
      hepatic portal triads, it raises the possibility that a process similar to
      fibrosis of the bone marrow may contribute to the hepatic fibrosis in DS.

PMID- 11530863
TI  - Cryopreservation of oocytes after vitrification.
AB  - Recently the majority of studies and research in the field of physiopathology of
      reproduction have been oriented towards cryopreservation of female eggs. This
      could resolve the ethical problems connected with the preservation of the embryo
      and with the gestation of the surplus oocytes collected after cycles of ovarian
      hyperstimulation. Notwithstanding that extraordinary results have been obtained
      in the field of cryopreservation of embryos and spermatozoa, the freezing of
      oocytes involves unfortunately many difficulties in relation, above all, to deep
      morphostructural and functional modifications which take place due to the low
      temperatures and to the toxic action of cryoprotective agents. The aim of this
      work was to test and then verify whether an efficient method of preserving the
      female egg cells by freezing in order to be able to subsequently use them for in
      vitro fertilization. The conclusions of this study, even if not highly
      encouraging, have allowed us to better evaluate the damage caused by low
      temperatures and at the same time should stimulate us and other researchers in
      this field to find new methods which will allow us to reach higher aspirations.

PMID- 11530864
TI  - Differential expression of Bcl-2 proto-oncogene in the trophoblast from embryos
      with Down's syndrome and those after spontaneous abortion.
AB  - Down's syndrome (trisomy 21) was the first human chromosomal syndrome to be
      recognized (in 1959 by Lejeune and colleagues). It is also the most frequent
      chromosomal aberration occurring in one out of 700 live newborns. In the present
      study we investigated the immunohistochemical expression of the apoptosis
      suppressing protein Bcl-2 in placental trophoblastic cells from embryos with
      Down's syndrome (gestational age 12th, 15th and 22nd week) and correlated the
      findings with equivalent trophoblastic cells from embryos after spontaneous
      abortion. In our cases with Down's syndrome a weak Bcl-2 expression was noted in
      the cytotrophoblast and syncytiotrophoblast of chorionic villi in contrast to
      strong Bcl-2 staining of the same cells in the cases of spontaneous abortions (p
      < 0.0001). Although there are no specific findings that truly characterize a
      placenta with trisomy, obtaining a small piece of chorionic villus tissue
      (chorionic villus biopsy) and immunohistochemical control for Bcl-2 protein could
      be an additional prenatal examination available to the perinatologist to detect
      chromosomal abnormalities.

PMID- 11530865
TI  - Fetal thoracic aorta doppler in cases with intrauterine growth restriction.
AB  - PURPOSE: Considering the accompanying hemodynamic changes Doppler studies have
      recently been performed for early diagnosis of intrauterine growth restriction
      (IUGR) cases with high morbidity and mortality. In the present study, Doppler
      study of the fetal thoracic aorta was conducted and the sensitivity and
      specificity of the study was assessed in the diagnosis and follow-up of IUGR, as
      well as prediction of pregnancy outcome. METHODS: This study included 44 IUGR
      cases and 52 healthy pregnant women (as a control group); Doppler waveforms of
      the fetal aortas were used to predict fetal outcome in pregnancies complicated
      with IUGR. Due to the short interval between the diagnosis of IUGR and delivery,
      the Doppler measurement could be redone for only 11 pregnant women in the control
      group; Doppler measurement could be done twice. RESULTS: There was no significant
      difference between the study group and the control group in terms of maternal
      age. There were significant differences in terms of gestational age, birth
      weight, pulsatility index, blood pressure and first minute apgar score. Of the 44
      IUGR cases, there were additional pathologies such as hypertension, DM and
      oligohydroamniosis, while there was no significant malfunction in the control
      group. CONCLUSION: We observed a decrease in the aortic blood flow and a high
      pulsatility index, which was an independent variable in the IUGR group. A high PI
      was strongly correlated with bad pregnancy outcome, fetal distress and a high
      cesarean section rate.

PMID- 11530866
TI  - Expression of fibrillar proteins and vimentin in developing chorionic villi is
      related to fetal maturation.
AB  - Using an immunocytochemical technique, the extracellular matrix components
      fibronectin, vimentin, laminin and collagen type IV were investigated in human
      chorionic villi of various stages of development. Fibronectin and laminin were
      consistently positive throughout embryonic development. Vimentin and collagen
      type IV were negative in first and second trimester chorionic villi, but became
      positive in term placentas. With the exception of laminin, all extracellular
      matrix molecules were detected in the villous stroma and, with the exception of
      vimentin, they were localized in the basement membranes. Our data suggest that
      fibronectin and laminin are essential components of the villous structure, while
      the presence of vimentin and collagen type IV in the chorionic villi should be
      regarded as an indicator of fetal maturation.

PMID- 11530867
TI  - Early induction of labor with PGE2-intravaginal gel in premature rupture of
      membranes.
AB  - Results of induction of labor with PGE2-intravaginal gel in PROM, were evaluated
      considering the best management.

PMID- 11530868
TI  - Imprint cytology of non-specific granulomatous mastitis.
AB  - Non-specific granulomatous mastitis (NSGM) is a tumor-like inflammatory condition
      involving breast lobules. Its recognition is of great significance because of
      clinical masquerade to invasive carcinoma. A 25-year-old woman developed a
      palpable breast lump with clinical and mammographic findings suggestive of
      malignancy. Touch imprint cytology of the excised lump was consistent with a
      granulomatous inflammation while histopathological examination documented a NSGM
      with central necrosis. Clinical, radiologic and laboratory testing failed to
      identify any specific causative agent.

PMID- 11530869
TI  - Expression of laminin, type IV collagen and fibronectin molecules is related to
      embryonal skin and epidermal appendage morphogenesis.
AB  - Basement membrane zones are specialized sheets--like arrangements of
      extracellular matrix proteins and glycosaminoglycans, and act as an interface
      between parenchymal cells and support tissue. They separate epithelium,
      endothelium, muscle cells and Schwann cells from adjacent connective tissue
      stroma, and also from a limiting membrane in the central nervous system. They are
      involved in several cellular and biological processes, including adhesion,
      migration and cellular differentiation. Basement membranes have five major
      components: collagen type IV, laminin, heparan sulfate, entactin, and
      fibronectin. In addition, there are numerous minor and poorly characterized
      protein and glycosaminoglycan components. The various components of the basement
      membranes of the skin (collagen type IV, proteoglycans--heparan sulfate, laminin,
      entactin and fibronectin) are products of the epithelial (epidermal) cells. We
      studied immunohistochemically the origin, the first appearance and distribution
      of the adhesive extracellular glycoprotein laminin and the fibrillar proteins of
      the extracellular matrix collagen type IV and fibronectin in the basement
      membranes of fetal human skin between 12 to 21 weeks of gestational age.
      Additionally, we studied the expression of vimentin in the extracellular matrix
      of the epithelial/mesenchyme junction of the skin. This study demonstrates
      clearly that the expression of the antigens laminin, collagen type IV and
      fibronectin starts in the germinative epithelial cells of the skin at the bulbs
      of the hair follicles (12th week for fibronectin and 19th week for laminin and
      collagen type IV), and migrating progressively involves the epithelial epidermal
      cells of the covering skin, as well as, the basement membrane at the dermal
      epidermal junction in that region (between 20 to 21 weeks of gestational age).

PMID- 11530870
TI  - The effect of antenatal corticosteroid therapy on pregnancies complicated by
      premature rupture of membranes.
AB  - This study was carried out to examine the effect of antenatal corticosteroid
      therapy on pregnancies complicated by premature rupture of membranes (PROMs). For
      this purpose, 139 patients with a singleton pregnancy (27-34 weeks of gestation)
      complicated by PROMs were evaluated prospectively during the period January 1997
      to February 1999 at two Jordanian military hospitals (Prince Rhashed and Prince
      Zaid). Patients were allocated into two groups; Group 1 included 72 patients
      treated with dexamethsone (24 mg divided into 4 doses 12 hours apart), and Group
      2 which included 67 patients whoreceived no treatment (control group). All women
      were examined clinically and the diagnosis of PROMs was demonstrated using
      vaginal speculum, nitrazine paper examination and ultrasonography. All neonates
      were evaluated clinically, radiologically, and by laboratory investigations.
      Pearson's Chi-square and Fisher's exact tests were used to assess the
      significance of differences between the two study groups. Respiratory distress
      syndrome (RDS), necrotizing enterocolitis (NEC), intraventricular haemorrhage
      (IVH), and days of hospital stay were significantly reduced in premature infants
      of the corticosteroid treated women compared with the controls (p<0.04, p<0.04,
      p<0.04, and p<0.05, respectively). The perinatal mortality was significantly
      decreased among the corticosteroid treated group in the gestational subgroups 31
      32 and 33-34 weeks (p<0.04), and in all birth weight subgroups (p<0.03). RDS was
      statistically a significant factor which resulted in increased perinatal
      mortality in the control group (p=0.02). Regarding the occurrence of postpartum
      endometritis there was a statistically significant increase among the
      corticosteroid treated group compared with the controls (p<0.04). CONCLUSION:
      Antenatal corticosteroid therapy in pregnancies complicated by PROMs has a
      positive influencing effect on premature infants between 31 and 34 weeks of
      gestation, decreasing significantly the perinatal morbidity and mortality. It
      should be used with particular relevance to the developing world where surfactant
      is not available or where neonatal intensive care units are lacking.

PMID- 11530871
TI  - Non-immune hydrops fetalis in the first trimester: a review of 30 cases.
AB  - OBJECTIVE: To evaluate the etiology and outcome of non-immune hydrops fetalis
      diagnosed in the first trimester of pregnancy. METHODS: 30 cases with fetal
      hydrops diagnosed between 10 and 14 weeks of pregnancy at the prenatal diagnosis
      unit of Istanbul Medical Faculty were reviewed. Sonographic findings, fetal
      chromosome profiles, and outcomes were analyzed. RESULTS: NIHF was found to be
      associated with structural abnormalities in 25 (83.3%) cases, and chromosomal
      abnormalities in nine (47.3%) of the 19 analyzed cases. Nuchal translucency
      measurements were greater than 3 mm in 28 of the cases (93.3%), and cystic
      hygroma was the most common detected abnormality (n: 22; 73.3%). All pregnancies
      with nonimmune hydrops resulted in abortion, intrauterine fetal death, or
      termination of the pregnancy. CONCLUSION: Fetal hydrops diagnosed in the first
      trimester of gestation is associated with a higher incidence of aneuploidy, and
      it has a high mortality, even in fetuses with normal chromosomes.

PMID- 11530872
TI  - Clinical pregnancy in a woman of 45 years after gamete intrafallopian transfer
      (GIFT).
AB  - Clinical pregnancy in women over 44 years is rare in assisted reproductive
      technology (ART). A case of a 45-year-old woman with clinical pregnancy after
      GIFT is described.

PMID- 11530873
TI  - Expression of the intermediate filament vimentin and fibrillar proteins of the
      extracellular matrix related to embryonal heart development.
AB  - During organogenesis, the heart is one the first organs to develop and the
      earliest organ to function. The early appearance of cardiac activity in the
      tubular hearts of chick and rat embryos was noted many years ago. It arises from
      two plates of the splanchnic mesoderm which fuse to form a single tubular
      structure composed of endocardial and myocardial cells and, between them, the
      extracellular cardiac matrix. There is considerable variation in the formation of
      the extracellular matrix in the various regions of the heart during development.
      The endocardial lining cells of the vertebrate embryos show a regional
      specificity that remains an unexplained phenomenon in cardiac morphogenesis. The
      great majority of the endocardial lining cells remain epithlial. However, a
      restricted population of endothelial cells, lining the atrioventricular (AV)
      canal and the reputed proximal outflow tract (OT), transforms into mesenchyme;
      the latter being the reputed progenitor of the valves and membranous septa. The
      purpose of this study was to investigate the extracellular cardiac matrix of the
      human fetal heart in different regions and in various stages of development, and
      also the heterogeneity of the endocardial cell lining, in connection with the
      endothelial cells of other cardiac vessels. Identification of the mesenchymal
      cells/extracellular matrix was confirmed by immunohistochemical techniques using
      the following monoclonal antibodies: actin, desmin, vimentin, collagen IV and
      fibronectin. The present results provide evidence that the extracellular matrix
      of the heart is of mesodermal origin but at the level of the valves the
      mesenchyme is derived from the endothelial lining cells rather than the primitive
      mesenchyme.

PMID- 11530874
TI  - Biomagnetic activity in the female breast at various physiological states.
AB  - PURPOSE: To investigate the biomagnetic activity produced physiologically by the
      various normally occurring states of the female breast: puberty, reproductive
      age, pregnancy, lactation and menopause. METHOD: The mammary glands of 90 healthy
      women were examined using a Superconducting Quantum Interference Device (SQUID).
      RESULTS: Biomagnetic activity was low at puberty (105.46+/-3.77 fT/square
      root(Hz)) and the menopause (111.66+/-25.06 fT/square root(Hz)), but was high
      during the reproductive years (142.13+/-20.70 fT/square root(Hz)), particularly
      in the hyperplastic states of late pregnancy (221.86+/-12.14 fT/square root(Hz))
      and lactation (252.73+/-54.77 fT/square root(Hz)). The results were statistically
      significant (p<0.0001 ANOVA test). CONCLUSION: Our observations indicate the
      importance of SQUID in understanding the biomagnetic activity of the female
      breast at the various physiological states of life.

PMID- 11530875
TI  - Immunotherapy of acute myeloid leukemia.
AB  - Most patients with acute myeloid leukemia (AML) respond initially to combination
      chemotherapy but later relapse. These patients often die from progressive disease
      or toxicities of further chemotherapy. At relapse, the patients' blasts are
      usually resistant to the drugs to which the patient has been exposed and
      frequently to other cytotoxic agents as well. Nevertheless, a number of these
      patients may be salvaged and achieve remissions with allogeneic stem cell
      transplants. In such cases, the pre-transplant conditioning regimens do not
      appear to account for the entire anti-leukemic efficacy. Immunological mechanisms
      for blast killing appear critical. There is tissue culture, animal and clinical
      evidence that stimulated donor T cells can recognize and kill leukemic blasts
      through recognition of alloantigens, differentiation antigens or leukemia
      specific antigens as targets. We will review the molecular mechanisms for the
      generation of anti-leukemic T cells and discuss methods to improve the
      specificity and intensity of anti-leukemic T cell responses in the setting of
      allogeneic stem cell transplants, donor lymphocyte infusions, autologous anti
      leukemic T cell infusions, and vaccine use in AML patients.

PMID- 11530876
TI  - Phage displayed biomolecules as preventive and therapeutic agents.
AB  - Phage display is a powerful technology for selecting and engineering peptides and
      proteins expressed on the surface of filamentous bacteriophage. The advantages of
      phage display technology over other research tools and its' great potential have
      been demonstrated by successful application of phage display in diverse fields of
      biomedical/clinical research. In this review we will describe some recent
      developments in phage display, including new expression vectors, display formats,
      bioselection strategies and applications in pharmaceutical biotechnology. We
      highlight some important applications of phage display to identify disease- and
      pathogen-specific biomolecules, making particular emphasis on development of
      phage display-derived preventive and therapeutic vaccines.

PMID- 11530877
TI  - The application of phage display in allergy research: characterization of IgE,
      identification of allergens and development of novel therapeutics.
AB  - The ability to display IgE antibody fragments, allergens and peptides upon
      filamentous phage has increasingly been used in allergy research. This technique
      offers the opportunity to isolate and produce IgE antibody fragments specific for
      allergens. These antibody fragments can then be used to address fundamental
      issues regarding the development of IgE antibodies in allergic patients, at both
      the molecular and structural level. Random peptide display has greatly
      facilitated the discovery of epitopes recognized by serum IgE antibodies from
      allergic patients, and it is a definitive tool for investigating the IgE-epitope
      interaction. Whole allergens can also be displayed on phage. Selecting IgE
      binding phage from diverse cDNA libraries of allergens has assisted in the
      identification of new allergens and provided a source of purified allergens for
      the diagnosis of allergic diseases. Finally, phage display of antibody fragments
      and random peptides is currently providing a means by which the IgE antibody can
      be targeted as a potential treatment for allergy. This review highlights several
      studies which have utilized phage display methodology in the area of allergy
      research, and it discusses how the therapeutic potential of this approach may be
      exploited.

PMID- 11530878
TI  - Intracellular signaling by phospholipase D as a therapeutic target.
AB  - The pharmaceutical industry has recently focused on intracellular signaling as a
      means to integrate the multiple facets of complex disease states, such as
      inflammation, because these pathways respond to numerous extracellular signals
      and coordinate a collection of cell responses contributing to pathology. One
      critical aspect of intracellular signaling is regulation of key cell functions by
      lipid mediators, in particular the generation of a key mediator, phosphatidic
      acid (PA) via the hydrolysis of phosphatidylcholine by phospholipase D (PLD).
      Research in this field has intensified, due in part to the recent cloning and
      partial characterization of the two PLD isoforms in mammalian cells, and this
      work has contributed significantly to our understanding of events downstream of
      PA generation. It is these effector functions of PLD activity that make this
      pathway attractive as a therapeutic target while the biochemical properties of
      the PLD isozymes make them amenable to small molecule intervention. Recent
      studies indicate that PA, and its immediate metabolites diacylglycerol and lyso
      PA, affect numerous cellular pathways including ligand-mediated secretion,
      cytoskeletal reorganisations, respiratory burst, prostaglandin release, cell
      migration, cytokine release, and mitogenesis. This review summarises the data
      implicating signaling via PLD in these cell functions, obtained from: (i)
      molecular analyses of PLD/effector interactions, (ii) correlation between PA
      production and cell responses, (iii) experimental manipulation of PA levels, (iv)
      inhibition of PLD regulators, and (v) direct inhibition of PA production. The
      utility of targeting PLD signaling for the treatment of acute/chronic
      inflammation and other indications is discussed in light of these data.

PMID- 11530879
TI  - Role of thymidine phosphorylase in biomodulation of fluoropyrimidines.
AB  - Thymidine phosphorylase (TP) is a key enzyme in the activating pathway of 5'DFUR
      and capecitabine. On the other hand, TP is identical to platelet-derived
      endothelial cell growth factor (PD-ECGF) which is known to be an angiogenic
      factor. Recent studies show TP expression is increased in various malignancies
      compared with the surrounding normal tissues. These reports demonstrate that
      elevated TP expression indicates a predisposition for aggressive disease and/or
      poor prognosis. Therefore, it is a reasonable strategy to target TP in cancer
      treatment by using fluoropyrimidines including 5-fluorouracil (5FU), 5'DFUR and
      capecitabine. TP-mediated biomodulation of fluoropyrimidines to enhance their
      anti-tumor effects has been investigated. TP up-regulators including cytokines,
      anti-tumor drugs and X-ray irradiation significantly increase cytotoxicity of
      fluoropyrimidines. Also, transfection of TP cDNA significantly enhances
      cytotoxicity of fluoropyrimidines. Biomodulation of fluoropyrimidines is
      clinically successful in treating some malignancies. We report a review on roles
      of TP in biomodulation of fluoropyrimidines.

PMID- 11530880
TI  - Immuno-isolation in oncology--a mini-review.
AB  - Immuno-isolation provides a potentially safe and effective method of delivering
      recombinant therapeutic molecules. Its application as a drug-delivery platform
      for the treatment of cancer has shown promising developments recently. This
      review will summarize the principle and current progress of this novel therapy
      paradigm in oncology. In this approach, a non-autologous cell line is genetically
      modified to secrete a recombinant product with potential for tumor suppression.
      Such a cell line may be implanted without graft rejection into all patients with
      similar neoplastic disease. The immune protection is conferred by enclosure
      within immuno-isolating devices such as microcapsules whose permeability would
      allow passage of smaller molecules such as oxygen, nutrients and waste products
      as well as the desired therapeutic transgene product. However, large immune
      mediators such as complement, macrophages and lymphocytes responsible for graft
      rejection would be excluded. In this review, we will consider how this technology
      may be applied as a novel genetic tool for cancer treatment to deliver
      antibodies, cytokines, enzymes and growth factors for treatment of various types
      of cancer. These molecules can be delivered at low constitutive levels, thereby
      permitting long-term systemic delivery, maintaining biological activity over
      extended periods, and eliminating the costs of product purification. The current
      success of this strategy in cancer treatment will be reviewed in in vitro
      systems, in animal models of cancer, and in human clinical trials.

PMID- 11530881
TI  - Neural compensations after lesion of the cerebral cortex.
AB  - Functional improvement after cortical injury can be stimulated by various factors
      including experience, psychomotor stimulants, gonadal hormones, and neurotrophic
      factors. The timing of the administration of these factors may be critical,
      however. For example, factors such as gonadal hormones, nerve growth factor, or
      psychomotor stimulants may act to either enhance or retard recovery, depending
      upon the timing of administration. Nicotine, for instance, stimulates recovery if
      given after an injury but is without neuroprotective effect and may actually
      retard recovery if it is given only preinjury. A related timing problem concerns
      the interaction of different treatments. For example, behavioral therapies may
      act, in part, via their action in stimulating the endogenous production of
      trophic factors. Thus, combining behavioral therapies with pharmacological
      administration of compounds to increase the availability of trophic factors
      enhances functional outcome. Finally, anatomical evidence suggests that the
      mechanism of action of many treatments is through changes in dendritic
      arborization, which presumably reflects changes in synaptic organization. Factors
      that enhance dendritic change stimulate functional compensation, whereas factors
      that retard or block dendritic change block or retard compensation.

PMID- 11530882
TI  - The motor system: the whole and its parts.
AB  - Our knowledge of components of the human motor system has been growing steadily,
      but our understanding of its integration into a system is lagging behind. It is
      suggested that a combination of measurements of forces and movements of the motor
      system in a functionally meaningful environment in conjunction with computer
      simulations of the motor system may help us in understanding motor system
      properties. Neurotrauma can be seen as a natural deviation, with recovery as a
      slow path to yet another deviant state of the motor system. In that form they may
      be useful in explaining the close interaction between form and function of the
      human motor system.

PMID- 11530883
TI  - Exercise and training to optimize functional motor performance in stroke: driving
      neural reorganization?
AB  - Neurorehabilitation is increasingly taking account of scientific findings.
      Research areas directing stroke rehabilitation are neurophysiology; adaptability
      to use and activity; biomechanics; skill learning; and exercise science (task,
      context specificity). Understanding impairments and adaptations enables a
      reappraisal of interventions-for example, changes in motor control resulting from
      impairments (decreased descending inputs, reduced motor unit synchronization),
      secondary soft tissue changes (muscle length and stiffness changes) are
      adaptations to lesion and disuse. Changes in interventions include increasing
      emphasis on active exercise and task-specific training, active and passive
      methods of preserving muscle extensibility. Training has the potential to drive
      brain reorganization and to optimize functional performance. Research drives the
      development of training programs, and therapists are relying less on one-to-one,
      hands-on service delivery, making use of circuit training and group exercise and
      of technological advances (interactive computerized systems, treadmills) which
      increase time spent in active practice. Emphasis is on skill training, stressing
      cognitive engagement and practice, aiming to increase strength, control, skill,
      endurance, fitness, and social readjustment. Rehabilitation services remain slow
      to make the changes necessary to upgrade environments, attitudes, and
      rehabilitation methodologies to those shown to be more scientifically rational
      and for which there is evidence of effectiveness.

PMID- 11530884
TI  - Adaptability and flexibility of the human motor system: implications for
      neurological rehabilitation.
AB  - This article stresses the plasticity of the adult sensorimotor cortex in response
      to various injuries or environmental changes. The dominant role of sensory input
      is discussed. A number of studies are presented that show how input may lead to
      learning and change. Learning is discussed in relation to recovery. It is shown
      how concepts from the field of motor control and learning may be used for
      improving neurological rehabilitation. Specific attention is given to the
      variability of input, the meaningfulness of input, and the role of the learning
      context. The learning context and the application context should have essential
      characteristics in common, otherwise transfer of learning will be non-optimal. It
      is argued that learning landscapes are necessary in order to treat patients in
      such a way that the learned skills are transferable to situations outside the
      hospital.

PMID- 11530885
TI  - Discussion on possibilities for therapeutic intervention in children and adults
      with motor disorders.

PMID- 11530886
TI  - Normal and abnormal development of motor behavior: lessons from experiments in
      rats.
AB  - In this essay a few relevant aspects of the neural and behavioral development of
      the brain in the human and in the rat are reviewed and related to the
      consequences of lesions in the central and peripheral nervous system at early and
      later age. Movements initially are generated by local circuits in the spinal cord
      and without the involvement of descending projections. After birth, both in
      humans and in rats it seems that the development of postural control is the
      limiting factor for several motor behaviors to mature. Strong indications exist
      that the cerebellum is significantly involved in this control. Lesions in the CNS
      at early stages interfere with fundamental processes of neural development, such
      as the establishment of fiber connections and cell death patterns. Consequently,
      the functional effects are strongly dependent on the stage of development. The
      young and undisturbed CNS, on the other hand, has a much greater capacity than
      the adult nervous system for compensating abnormal reinnervation in the
      peripheral nervous system. Animal experiments indicated that the cerebellar
      cortex might play an important part in this compensation. This possibility should
      be investigated further as it might offer important perspectives for treatment in
      the human.

PMID- 11530887
TI  - Early brain damage and the development of motor behavior in children: clues for
      therapeutic intervention?
AB  - The Neuronal Group Selection Theory (NGST) could offer new insights into the
      mechanisms directing motor disorders, such as cerebral palsy and developmental
      coordination disorder. According to NGST, normal motor development is
      characterized by two phases of variability. Variation is not at random but
      determined by criteria set by genetic information. Development starts with the
      phase of primary variability, during which variation in motor behavior is not
      geared to external conditions. At function-specific ages secondary variability
      starts, during which motor performance can be adapted to specific situations. In
      both forms, of variability, selection on the basis of afferent information plays
      a significant role. From the NGST point of view, children with pre- or
      perinatally acquired brain damage, such as children with cerebral palsy and part
      of the children with developmental coordination disorder, suffer from stereotyped
      motor behavior, produced by a limited repertoire or primary (sub)cortical
      neuronal networks. These children also have problems in selecting the most
      efficient neuronal activity, due to deficits in the processing of sensory
      information. Therefore, NGST suggests that intervention in these children at
      early age should aim at an enlargement of the primary neuronal networks. With
      increasing age, the emphasis of intervention could shift to the provision of
      ample opportunities for active practice, which might form a compensation for the
      impaired selection.

PMID- 11530888
TI  - People with cerebral palsy: effects of and perspectives for therapy.
AB  - The movement disorder of cerebral palsy (CP) is expressed in a variety of ways
      and to varying degrees in each individual. The condition has become more complex
      over the last 20 years with the increasing survival of children born at less than
      28 to 30 weeks gestational age. Impairments present in children with CP as a
      direct result of the brain injury or occurring indirectly to compensate for
      underlying problems include abnormal muscle tone; weakness and lack of fitness;
      limited variety of muscle synergies; contracture and altered biomechanics, the
      net result being limited functional ability. Other contributors to the motor
      disorder include sensory, cognitive and perceptual impairments. In recent years
      understanding of the motor problem has increased, but less is known about effects
      of therapy. Evidence suggests that therapy can improve functional possibilities
      for children with cerebral palsy but is inconclusive as to which approach might
      be most beneficial. The therapist requires an understanding of the interaction of
      all systems, cognitive/perceptual, motor, musculoskeletal, sensory and
      behavioral, in the context of the development and plasticity of the CNS. It is
      necessary to understand the limitations of the damaged immature nervous system,
      but important to optimize the child's functional possibilities.

PMID- 11530889
TI  - Changes in muscles and tendons due to neural motor disorders: implications for
      therapeutic intervention.
AB  - Patients with an upper motor neurone syndrome (CP) suffer from many disabling
      primary symptoms: spasms, weakness, and loss of dexterity. These primary
      'neurogenic' symptoms often lead to secondary disabilities, muscle contractures,
      and tertiary effects, bone deformations. A common symptom of CP is hypertonia,
      with the consequence that the involved muscles remain in an excessively shortened
      length for most of the time. As a normal reaction of the muscle tissue, the
      number of sarcomeres is reduced and the muscle fibers shorten permanently: a
      contracture develops. A possible second type of contracture is that normal muscle
      lengthening along with bone growth is affected. Current treatments for the
      secondary effects include (1) reduction of muscle force, (2) lengthening of the
      muscle fibers by serial plaster casts, and (3) surgical lengthening of tendons or
      aponeurosis. The choice of treatment depends on the cause of the functional
      deficit. Bone tissue also adapts itself to abnormal forces, especially in the
      growth period. The hypertonias or contractures of CP so may give rise to bone
      malformations that interfere with function (e.g. femur endorotation) or may
      reduce the action of muscles by changing the lever arm (e.g. ankle varus).
      Although prevention should always be preferred, a timely surgical intervention
      cannot always be avoided. The differences in treatment for the various groups
      require and justify an extensive laboratory investigation, including EMG
      recordings in gait, measurement of passive elastic properties, and long-term
      observation of the hypertonia.

PMID- 11530890
TI  - Spinal cord lesion: effects of and perspectives for treatment.
AB  - Following central motor lesions, two forms of adaptation can be observed which
      lead to improved mobility: (1) the development of spastic muscle tone, and (2)
      the activation of spinal locomotor centers induced by specific treadmill
      training. Tension development during spastic gait is different from that during
      normal gait and appears to be independent of exaggerated monosynaptic stretch
      reflexes. Exaggerated stretch reflexes are associated with an absence or
      reduction of functionally essential polysynaptic reflexes. When supraspinal
      control of spinal reflexes is impaired, the inhibition of monosynaptic reflexes
      is missing in addition to a reduced facilitation of polysynaptic reflexes.
      Therefore, overall leg muscle activity becomes reduced and less well modulated in
      patients with spasticity. Electrophysiological and histological studies have
      shown that a transformation of motor units takes place following central motor
      lesions with the consequence that regulation of muscle tone is achieved at a
      lower level of neuronal organization which in turn enables the patient to walk.
      Based on observations of the locomotor capacity of the spinal cat, recent studies
      have indicated that spinal locomotor centers can be activated and trained in
      patients with complete or incomplete paraplegia when the body is partially
      unloaded. However, the level of electromyographic activity in the gastrocnemius
      (the main antigravity muscle during gait) is considerably lower in the patients
      compared to healthy subjects. During the course of a daily locomotor training
      program, the amplitude of gastrocnemius, electromyographic activity increases
      significantly during the stance phase, while inappropriate tibialis anterior
      activation decreases. Patients with incomplete paraplegia benefit from such
      training programs such that their walking ability on a stationary surface
      improves. The pathophysiology and functional significance of spastic muscle tone
      and the effects of treadmill training on the locomotor pattern underlying new
      attempts to improve the mobility of patients with paraplegia are reviewed.

PMID- 11530891
TI  - Physiology and pathophysiology of the swallowing area of human motor cortex.
AB  - Swallowing problems can affect as many as one in three patients in the period
      immediately after stroke. Despite this, in the majority of cases, recovery
      usually occurs to a safe level after a month or two. In this review, we show how
      the organization of the cortical projections to swallowing muscles can account
      for many of the clinical observations on swallowing after stroke and explain why
      recovery is common in the long term. In addition, we examine approaches that may
      be useful in speeding up recovery of swallowing. Swallowing may be a useful model
      in which to study central nervous reorganization after injury.

PMID- 11530892
TI  - Parkinson's disease: clinical signs and symptoms, neural mechanisms, positron
      emission tomography, and therapeutic interventions.
AB  - Parkinson's disease is one of the most frequent neurodegenerative brain diseases.
      Its time course is slow and is characterized by progressive loss of dopaminergic
      and other brainstem neurons resulting in malfunctioning of the cerebral neuronal
      systems responsible for motor functions. The clinical signs are slowness of
      movement, muscle rigidity and rest-tremor amongst other features. The cause of
      the disease is unknown, but recently involvement of genetic factors is being
      researched. Positron emission tomography (PET) allows in vivo determination of
      striatal dopaminergic activity. This has increased our insight in the
      pathophysiology of the disease and permits direct study of disease progression at
      a biochemical level and equally to monitor whether potential neuroprotective
      interventions are indeed effective. Thus far no drug has emerged but promising
      substances are currently being studied.

PMID- 11530893
TI  - A retrospective study of children's perceptions of participation as clinical
      research subjects in a minimal risk study.
AB  - The purpose of the study was to evaluate children's perceptions of their
      participation as research subjects in a minimal risk research study (a
      methylphenidate population pharmacokinetic study conducted 8 months earlier). We
      identified 115 children of an original 189, aged 6 to 19 years, who were
      responding well to regular methylphenidate for attention-deficit hyperactivity
      disorder. By using a structured format, telephone interviewers unconnected to the
      original study questioned the children about what it had been like to be a
      subject in terms of voluntariness, accuracy of informed consent, reasons for
      participating, and satisfaction with their experience. Children overwhelmingly
      perceived their involvement as voluntary (89%) and the information about the
      study as accurately presented (80%), and they reported a high level of
      satisfaction with their participation (97%). Self-interest was the most
      frequently reported reason for participation (47%). In a subsample of 25
      children, the percentage of agreement of a 1-week test-retest equaled or exceeded
      72% for all answers.

PMID- 11530894
TI  - Prenatal tobacco effects on neuropsychological outcomes among preadolescents.
AB  - This study evaluated the relationships between maternal smoking during pregnancy
      and 10-year-old children's performance on measures of learning, memory, and
      problem-solving. In this prospective cohort study, mothers were recruited from an
      urban prenatal clinic in 1982 and 1983 and observed from their fourth prenatal
      month until the time of the study. At the 10-year visit, 593 children and mothers
      were evaluated. The prevalence of tobacco use was high in this cohort: 54.3%,
      53.3%, and 60% of the women smoked in the first trimester, third trimester, and
      10-year assessment, respectively. After controlling statistically for other
      prenatal substance use, current tobacco, other substance use variables, and
      multiple sociodemographic covariates, prenatal tobacco exposure was significantly
      associated with deficits in learning and memory. Specifically, prenatal tobacco
      exposure was associated with deficits in verbal learning and design memory, as
      well as slowed responding on a test of eye-hand coordination. In addition, these
      children demonstrated a reduced ability for flexible problem solving and more
      impulsivity, as indicated by an increase in perseverative responses on a card
      sorting test. Prenatally exposed children did not show attention deficits or
      increased activity on a continuous performance test.

PMID- 11530895
TI  - Night waking, sleep-wake organization, and self-soothing in the first year of
      life.
AB  - Few objective data are available regarding infants' night waking behaviors and
      the development of self-soothing during the first year of life. This cross
      sectional study examined 80 infants in one of four age groups (3, 6, 9, or 12 mo)
      for four nights by using videosomnography to code nighttime awakenings and parent
      child interactions. A large degree of variability was observed in parents'
      putting the infant to bed awake or asleep and in responding to vocalizations
      after nighttime awakenings. Most infants woke during the night at all ages
      observed. Younger infants tended to require parental intervention at night to
      return to sleep, whereas older infants exhibited a greater proportion of self
      soothing after nighttime awakenings. However, even in the 12-month-old group, 50%
      of infants typically required parental intervention to get back to sleep after
      waking. Results emphasize the individual and contextual factors that effect the
      development of self-soothing behavior during the first year of life.

PMID- 11530896
TI  - A comparison of individual and family psychology of adolescents with chronic
      fatigue syndrome, rheumatoid arthritis, and mood disorders.
AB  - Chronic fatigue syndrome (CFS) is a controversial diagnosis with unknown cause.
      Adult studies indicate high rates of psychosocial dysfunction and psychiatric
      comorbidity. The authors compared three groups of pediatric patients selected by
      diagnosis-(1l) CFS (n = 15), (2) juvenile rheumatoid arthritis (n = 15), and (3)
      mood disorders (n = 15)-across many psychological measures. CFS subjects had
      dramatic elevation of the Somatic Complaints subscale (mean T score = 75),
      whereas the mood disorders group had higher externalizing scores (mean T score =
      68) on the Child Behavior Checklist. The CFS subjects missed significantly more
      school compared with the two control groups. After the onset of CFS, 13 of 15 of
      the CFS patients required significant educational accommodation. Only 4 of the 15
      CFS patients had an Axis I psychiatric diagnosis, as determined by the
      Computerized Diagnostic Interview for Children. Despite a low rate of psychiatric
      diagnosis in the CFS sample, these data attest to their psychosocial and school
      dysfunction.

PMID- 11530897
TI  - An 8-year-old boy with school difficulties and " odd behavior".

PMID- 11530898
TI  - The measurement of quality of life in children: past and future perspectives.
AB  - Quality of life (QoL) is central to pediatric practice. Where it is possible to
      manage but not cure a disease, it is important to determine how far treatment and
      disease compromise the child's QoL. In this way, informed judgments can be made
      about whether or not treatment is appropriate, and, where there is a choice,
      which choice might be the best option for the child. In this review, we consider
      different approaches to measuring child QoL, report a methodological review of
      measures currently available, evaluate the quality of these measures, and finally
      consider the implications for the future development and use of QoL measures.
      Computer searches identified 269 potentially relevant articles, of which 137 were
      included in the review. Of these, 43 were primarily concerned with the
      development of a new measure of QoL, 79 reported subsequent development of these
      same measures, and 15 used a battery approach to measure QoL. All currently
      available measures have limitations (e.g., limited psychometric data, lack of
      parallel forms for children and proxy raters, and insufficient attention to
      children's ability to complete paper-and-pencil measures). However,
      recommendations are made on the basis of those considered to be most
      satisfactory. It is essential that attempts be made to use QoL measures in
      research (e.g., evaluation of clinical trials and alternative treatments) to gain
      experience that will guide development of a second generation of more
      sophisticated measures. Despite the practical difficulties identified,
      measurement of QoL remains of central interest to all those concerned with the
      well-being of children.

PMID- 11530899
TI  - Assessing TB control options: the ISG reports on progress to date.

PMID- 11530900
TI  - Screening badgers (Meles meles) for Mycobacterium bovis infection by using
      multiple applications of an ELISA.
AB  - The current indirect ELISA used to evaluate whether live badgers are infected
      with Mycobacterium bovis has a low sensitivity (40.7 per cent), but a relatively
      high specificity (94.3 per cent). The low sensitivity of the test makes the
      diagnosis unreliable, but its sensitivity can be increased by using multiple
      tests. Two multiple testing procedures (involving up to three sequential tests)
      were investigated. A procedure in which two positive results were required from
      three tests before an animal was declared positive resulted in a lower
      sensitivity, but a higher specificity than the single test (38 and 98 per cent
      respectively). A more rigorous procedure, in which only one positive result was
      required from three tests, resulted in a marked increase in sensitivity but a
      slight reduction in specificity (79.5 and 83.1 per cent respectively) when
      compared to the single test.

PMID- 11530901
TI  - Critical points in the transport of cattle to slaughter in Spain that may
      compromise the animals' welfare.
AB  - The welfare of cattle depends greatly on the attitudes and training of
      stockpersons and on the availability of appropriate facilities. Much has been
      learned about stress during transport, but less attention has been paid to
      identifying and correcting critical points, partly because they vary widely both
      nationally and internationally. A survey of cattle transport in Spain was made in
      an effort to determine which parts of the process most compromised the animals'
      welfare. Data were collected on the methods and facilities for loading and
      unloading, transport times, types of vehicle and slaughterhouse practices.
      Loading facilities were adequate and loading times generally short but some farms
      continued to use an electric goad and weather-proofing was generally poor. The
      average journey time within Spain was three-and-a-half hours, but many trips were
      made abroad (especially to Italy), few drivers received specific training courses
      and the types and quality of vehicles varied widely. The average unloading time
      was very short but the animals were not always inspected for injuries or
      dirtiness. Lairage times were normally more than eight hours but few
      slaughterhouses had air-conditioning equipment to prevent excessive heat or
      dehydration. Almost all stockpersons avoided either regrouping animals or housing
      or transporting animals at high densities.

PMID- 11530902
TI  - Evaluation of the potential causes of epistaxis in dogs with natural visceral
      leishmaniasis.
AB  - Haemostasis was evaluated in 19 dogs with natural Leishmania infection, six of
      them with a history of epistaxis, and the results were compared with the results
      from 24 healthy dogs. In addition, the dogs' blood pressure was measured and
      biopsies were taken from the nasal mucosa. Buccal mucosa bleeding time was
      prolonged in the dogs with leishmaniasis (P < 0.002) and most significantly in
      those with epistaxis (P < 0.005). None of the Leishmania-infected dogs had
      thrombocytopenia, low levels of plasma von Willebrand factor antigen, a prolonged
      prothrombin time or activated partial thromboplastin time, a low plasma
      fibrinogen concentration or high serum fibrin degradation products. These results
      rule out defects of secondary haemostasis or disseminated intravascular
      coagulation as significant causes of epistaxis in non-complicated leishmaniasis.
      Histopathology of the nasal mucosa of 10 of the affected dogs, three of them with
      epistaxis, revealed ulcerative and inflammatory lesions in all of them.

PMID- 11530903
TI  - Nodavirus infection in Atlantic cod and Dover sole in the UK.

PMID- 11530904
TI  - Variability in residue concentrations of tilmicosin in cattle muscle.

PMID- 11530905
TI  - Salinomycin poisoning in veal calves.

PMID- 11530906
TI  - Diagnosis of secondary hyperparathyroidism in a pony using intact parathyroid
      hormone radioimmunoassay.

PMID- 11530907
TI  - Two cases of ventricular foreign bodies in the kori bustard (Ardeotis kori).

PMID- 11530908
TI  - Role of veterinary nurses.

PMID- 11530909
TI  - DEFRA's proposals on equine dentistry.

PMID- 11530910
TI  - Kidney transplants in cats.

PMID- 11530911
TI  - Kidney transplants in cats.

PMID- 11530912
TI  - Kidney transplants in cats.

PMID- 11530913
TI  - Johne's disease control programmes.

PMID- 11530914
TI  - Effects of serial radiography on juvenile bustards.

PMID- 11530915
TI  - Removal of an airborne low volatility metal under fuel-rich and fuel lean
      conditions through condensation onto soot and/or sorbent particles.
AB  - The removal by a sorbent of a low volatility heavy metal, barium, from a
      combustor exhaust stream was investigated experimentally. The barium was
      introduced into the gas phase through a combustion process simulating
      incineration of waste materials. Sorbent- and metal-feed-rate, temperature and
      air intake were varied to study the impact on the gas-to-particle conversion and
      the metal condensation process. Peak temperature and subsequent temperature drop
      were found to be the dominant factors affecting the condensation process. Fuel
      rich and fuel-lean conditions result in lower peak temperatures and a more rapid
      temperature drop relative to stoichiometric conditions. Since the metal vapor
      saturation pressure falls exponentially with temperature a larger condensation
      rate was observed, as long as nucleation was suppressed. Fuel-rich conditions
      promote the formation of soot particles. These particles function as sites for
      subsequent metal-species condensation. Chlorine was injected into the flow, to
      study the effect on metal vaporization. Chlorine promoted the volatilization of
      barium and therefore the subsequent condensation capture was made more effective.

PMID- 11530916
TI  - Pyrolysis kinetics of waste PVC pipe.
AB  - The pyrolysis kinetics of waste PVC pipe was investigated with a thermal
      gravimetric analysis system at heating rates of 5, 10, and 30 degrees C/min in a
      nitrogen atmosphere. Freeman-Carroll method was employed to evaluate kinetic
      parameters. Two dominant peaks were observed on derivative gravimetric curves,
      hypothetically suggesting a two-stage apparent reaction model. The first-stage
      reaction was likely to be represented by stoichiometric reaction to yield
      volatiles (mainly HCl) and intermediates. The second-stage reaction might be
      described by thermal degradation of intermediates competitively into gas, liquid,
      and solid by-products. Quasi-isothermal operations were introduced to verify the
      reaction types of the first and second reaction. The generation reaction of
      intermediates achieved at lower temperatures was carried out independently with
      their decomposition reaction at higher temperatures. The effects of additives on
      the pyrolysis kinetics of waste PVC pipe seem to be significant, especially on
      the first-stage reaction. The first-stage reaction was retarded. A merged peak at
      low temperatures was observed on the derivative thermogravimetry (DTG) curve
      instead of two peaks usually observed for that of pure PVC resin. The first peak
      on the DTG curve of pure PVC resin may shift more, resulting in the complete
      overlap of two peaks. The quantity of evolved HCl was likely to decrease because
      of interaction of metal components of stabilizers with either HCl or active
      chlorine atom or both. The final residual fraction increased as a result of
      pyrolysis of organic forms of additives to yield extra char. On the other hand,
      the second-stage reaction kinetics demonstrates a similar pattern to that of pure
      PVC resin, implying that the effects of additives may be less significant in
      comparison with that at the first-stage reaction.

PMID- 11530917
TI  - Perpetual landfilling through aeration of the waste mass; lessons from test cells
      in Georgia (USA).
AB  - Municipal solid waste (MSW) landfills worldwide are experiencing the consequences
      of conventional landfilling techniques, whereby anaerobic conditions are created
      within the landfilled waste. Under anaerobic conditions within a landfill site
      slow stabilization of the waste mass occurs, producing methane, (an explosive
      'green house' gas) and leachate (which can pollute groundwater) over long periods
      of time. As a potential solution, it was demonstrated that the aerobic
      degradation of MSW within a landfill can significantly increase the rate of waste
      decomposition and settlement, decrease the methane production and leachate
      leaving the system, and potentially increase the operational life of the site.
      Readily integrated into the existing landfill infrastructure, this approach can
      safely and cost-effectively convert a MSW landfill from anaerobic to aerobic
      degradation processes, thereby effectively composting much of the organic
      portions (one of the potentially polluting elements in a conventional landfill
      site) of the waste. This paper summarizes the successful results of two separate
      aerobic landfill projects located in Georgia (USA) and discusses the potential
      economic and environmental impacts to worldwide solid waste management practices.

PMID- 11530918
TI  - Use of steel converter slag as nickel adsorber to wastewater treatment.
AB  - Magnetite, the main component of converter slag in the steel industry, can be
      used for the adsorption of Ni(II) from aqueous solutions, over a range of
      conditions: initial metal concentration (10-100 mg 1(-1)), stirring times (2-240
      min), adsorbent dosage (1 g for 0.5 1 of metal solution) and temperatures (20, 30
      and 38 degrees C). The adsorption rate increased with initial concentration but
      decreased with increase in temperature, due to competition of the dissolution
      process. The adsorption process obeyed the Freundlich isotherm model.

PMID- 11530919
TI  - Treatment of chromium plating process effluents with ion exchange resins.
AB  - The surface treatment industry deals with various heavy metals, including the
      elements Cr, Zn, Ni, Cd, and Cu. Conventional treatments of effluents generate
      class I solid residue. The aim of this investigation was to study the viability
      of ion exchange as an alternative process for treatment of rinse water and to
      determine the efficacy of two ion exchange systems, System 1: "strong" cationic
      resin-"strong" anionic resin and System 2: "strong" cationic resin-"weak" anionic
      resin. Commercial resins and solutions taken from rinse tanks of chromium plating
      companies were used in this investigation. A two-column system, one for the
      cationic resin and another for the anionic resin, both with 150 ml capacity was
      mounted. The solution was percolated at a rate of 10 ml/min. The following
      solutions were used for regeneration of the resins: 2% H2SO4 for the cationic and
      4% NaOH for the anionic. The percolated solutions revealed chromium contents of
      less than 0.25 mg/l, independent of the system used. The "strong" cationic resin
      "weak" anionic resin gave excellent regeneration results. The "strong" cationic
      "strong" anionic resin presented problems during regeneration, and did not
      release the retained ions after percolation of 2000 ml of 4% NaOH solution. It is
      concluded that for this type of treatment, the system composed of "strong"
      cationic resin and "weak" anionic resin is more appropriate.

PMID- 11530920
TI  - Anaerobic biotransformation and methane generation potential of cheese whey in
      batch and UASB reactors.
AB  - Anaerobic treatability and methane generation potential of cheese whey were
      determined in batch reactors. Furthermore, the effect of nutrient and trace metal
      supplementation on the batch anaerobic treatment, and the high-rate anaerobic
      treatability of cheese whey in upflow anaerobic sludge blanket (UASB) reactors
      were investigated. To this purpose biochemical methane potential experiments were
      conducted and single- and two-stage UASB reactors with granular cultures were
      operated. In UASB experiments significance of process staging, operational
      parameters such as hydraulic retention time (HRT), influent chemical oxygen
      demand (COD) concentration and loading rate were also investigated. The results
      revealed that nutrient and trace metal supplementation is vital for the anaerobic
      treatment of cheese whey; the anaerobic methane generation for the cheese whey
      studied was found to be 424 ml CH4/g COD (23.4 1 CH4/l cheese whey); undiluted
      cheese whey could be treated anaerobically at relatively short HRT values (2.06
      4.95 days) without any significant stability problems; HRT values as low as 2-3
      days can be used for the anaerobic treatment of cheese whey, with a COD removal
      efficiency of 95-97% at influent COD concentration of 42 700 +/- 141-55 100 +/-
      283 mg/l.

PMID- 11530921
TI  - Stabilization of chloro-organics using organophilic bentonite in a cement-blast
      furnace slag matrix.
AB  - The application of cement-based stabilisation/solidification treatment to organic
      containing wastes is made difficult by the adverse effect of organics on cement
      hydration. The use of organophilic clays as pre-solidification adsorbents of the
      organic compounds can reduce this problem because of the high adsorption power of
      these clays and their compatibility with the cementitious matrix. This work
      presents an investigation of the effect on hydration kinetics, physico-mechanical
      properties and leaching behaviour of cement-based solidified waste forms
      containing 2-chlorophenol and 1-chloronapthalene adsorbed on organophilic
      bentonites. These were prepared by cation exchange with
      benzyldimethyloctadecylammonium chloride and trimethyloctadecylammonium chloride.
      The binder was a 30% pozzolanic cement, 70% granulated blast furnace slag
      mixture. Several binder-to-bentonite ratios and different concentrations of the
      organics on the bentonite were used. Kinetics of hydration were studied by
      measurement of chemically bound water and by means of thermal and calorimetric
      analyses. Microstructure and other physico-mechanical properties of the
      solidified forms were studied by means of mercury intrusion porosimetry, scanning
      electron microscopy and unconfined compressive strength measurement. Leaching was
      checked by two different leaching tests: one dynamic, on monolithic samples, and
      the other static, on powdered samples. This study indicates that the
      incorporation of the organic-loaded bentonite in the binder matrix causes
      modifications in the hardened samples by altering cement hydration. The effects
      of the two organic contaminants are differentiated.

PMID- 11530922
TI  - Contamination of the environment by the current disposal methods of mercury
      containing lamps in the state of Minas Gerais, Brazil.
AB  - This survey describes the degree of environmental contamination resulting from
      the current disposal methods of mercury-containing lamps. The territory studied
      for this purpose is the federal state of Minas Gerais, one of the most populated
      areas in the Brazilian federation of states. The results of this survey derive in
      part from answers received to a questionnaire mailed out to industrial firms,
      commercial business enterprises, hospitals and departments of public work. The
      sampling technique used was a nonprobabilistic (purposive sampling). Three types
      of disposal were found to prevail: (1) as an addition to corporate waste disposal
      (garbage), (2) recycling and (3) disposal by other methods. Overall, our study
      shows that the majority of mercury lamps are being disposed in the metropolitan
      area of Belo Horizonte, primarily by the public sector, followed by industrial,
      commercial and hospital sectors. Although recycling constitutes a relatively high
      fraction of the disposal methods, we find Federal regulations in Brazil regarding
      the disposal of hazardous, mercury-containing lamps to be far behind the state of
      technological achievement. This gap has permitted the adoption of disposal
      measures that are obsolete, incorrect, and a primary cause for the extensive
      contamination of the ecosystems with harmful effects to human health.

PMID- 11530923
TI  - Kinetics and thermodynamics of copper ions removal from wastewater by use of
      zeolite.
AB  - Natural Bulgarian zeolite was tested for its ability to remove Cu2+ from model
      wastewater. Influence of process variables was investigated. It was found that
      the optimum wastewater to zeolite ratio is 100:1 and the optimum pH value of
      water to be treated is 5.5 to 7.5. Zeolite with finer particles shows a higher
      uptake capacity. The simultaneous presence of Ca2+ and Mg2+ in concentrations
      similar to their concentrations in Bulgarian natural water does not significantly
      influence the uptake of Cu2+. Zeolite modification by treating it with NaCl,
      CH3COONa and NaOH increases its uptake ability. Copper ions are strongly
      immobilized by modified zeolite and secondary pollution of water caused by its
      contact with preloaded zeolite is very low (1.5-2.5% of Cu2+ preliminary
      immobilized have been released back into acidified water). Contacting with 2 mol
      dm(-3) NaCl can easily regenerate loaded zeolite; best results were obtained for
      zeolite modified with NaCl. Requirements of Bulgarian standards for industrial
      wastewater can be met by a one-stage process for an initial Cu2+ concentration of
      10 mg dm(-3), and by a two stage process for an initial Cu2+ concentration of 50
      mg dm(-3). Uptake of Cu2+ by zeolite from neutral wastewater has proved to be as
      effective as Cu2+ removal by precipitation of copper hydroxide. The process of
      Cu2+ uptake by natural zeolite is best described by the kinetic equation for
      adsorption. This fact, together with the correlation found between the Cu2+
      uptake and the amount of Na+, Ca2+ and K+ released into solution by zeolite shows
      that the ion exchange sorption plays the basic role in Cu2+ uptake by natural
      zeolite. The value obtained for the apparent activation energy (26.112 kJ mol(-1)
      implies that the process can be easily carried out with a satisfactory rate. The
      uptake equilibrium is best described by the Langmuir adsorption isotherm, with
      Langmuir constants KL= 6.4 x 10(-2) dm3 mg(-1) and M = 6.74 mg g(-1). The
      apparent equilibrium constant found shows moderate affinity of zeolite for Cu2+.
      Values of deltaG degrees and deltaH degrees found show the spontaneous and
      endothermic nature of the process of Cu2+ uptake by natural zeolite.

PMID- 11530924
TI  - Field tracer-transport tests in unsaturated fractured tuff.
AB  - This paper presents the results of a field investigation in the unsaturated,
      fractured welded tuff within the Exploratory Studies Facility (ESF) at Yucca
      Mountain, NV. This investigation included a series of tests during which tracer
      laced water was released into a high-permeability zone within a horizontal
      injection borehole. The tracer concentration was monitored in the seepage
      collected in an excavated slot about 1.6 m below the borehole. Results showed
      significant variability in the hydrologic response of fractures and the matrix.
      Analyses of the breakthrough curves suggest that flow and transport pathways are
      dynamic, rather than fixed, and related to liquid-release rates. Under high
      release rates, fractures acted as the predominant flow pathways, with limited
      fracture-matrix interaction. Under low release rates, fracture flow was
      comparatively less dominant, with a noticeable contribution from matrix flow.
      Observations of tracer concentrations rebounding in seepage water, following an
      interruption of flow, provided evidence of mass exchange between the fast-flowing
      fractures and slow- or non-flowing regions. The tests also showed the
      applicability of fluorinated benzoate tracers in situations where multiple
      tracers of similar physical properties are warranted.

PMID- 11530925
TI  - Grid lysimeter study of steady state chloride transport in two Spodosol types
      using TDR and wick samplers.
AB  - Solute transport in soils is affected by soil layering and soil-specific
      morphological properties. We studied solute transport in two sandy Spodosols: a
      dry Spodosol developed under oxidizing conditions of relatively deep groundwater
      and a wet Spodosol under periodically reducing conditions above a shallow
      groundwater table. The wet Spodosol is characterized by a diffuse and
      heterogeneous humus-B-horizon (i.e., Spodic horizon), whereas the dry Spodosol
      has a sharp Spodic horizon. Drainage fluxes were moderately variable with a
      coefficient of variation (CV) of 25% in the wet Spodosol and 17% in the dry
      Spodosol. Solute transport in 1-m-long and 0.8-m-diameter soil columns was
      investigated using spatial averages of solute concentrations measured by a
      network of 36 Time Domain Reflectometry (TDR) probes. In the dry Spodosol, solute
      transport evolves from stochastic-convective to convective-dispersive at a depth
      of 0.25 m, coinciding with the depth of the Spodic horizon. Chloride breakthrough
      at the bottom of the soil columns was adequately well predicted by a convection
      dispersion model. In the wet Spodosol, solute transport was heterogeneous over
      the entire depth of the column. Chloride breakthrough at 1 m depth was predicted
      best using a stochastic-convective transport model. The TDR sampling volume of 36
      probes was too small to capture the heterogeneous flow and concomitant transport
      in the wet Spodosol.

PMID- 11530926
TI  - Multiphase flow and transport in fractured clay/sand sequences.
AB  - A numerical model (Queen's University Multi-Phase Flow Simulator, QUMPFS) was
      used to assess the rate of trichloroethylene (TCE) dense, non-aqueous phase
      liquid (DNAPL) migration through fractured clay, with special attention focused
      on the influence of interbedded sand lenses. The presence of these sand lenses
      was found to increase the time required for the non-wetting phase to migrate
      through the full 30 m vertical extent of the clay sequence from a few days to
      several years. Applied vertical hydraulic gradients were found to be moderately
      influential in systems consisting solely of fractured clays, yet one of the
      dominant factors controlling speed of vertical migration when sand lenses were
      present. Larger displacement pressure of the sands relative to that of the
      fractures leads to slower DNAPL migration rates, due to the delays that occur
      during build-up of capillary pressures. Dissolution of DNAPL and subsequent
      matrix diffusion of the aqueous phase has little effect on the rate of DNAPL
      migration through systems consisting of fractured clay only, yet slows the rate
      of migration in systems containing sand lenses. In all cases examined, the rate
      of DNAPL loading to the lower aquifer far exceeded the rate of aqueous phase mass
      loading. It was also found that DNAPL reaches the lower aquifer at approximately
      the same time as the aqueous phase plumes even for systems experiencing downward
      groundwater flow due to the attenuation of the aqueous phase through matrix
      diffusion.

PMID- 11530927
TI  - Investigation of surfactant-enhanced dissolution of entrapped nonaqueous phase
      liquid chemicals in a two-dimensional groundwater flow field.
AB  - Because of their low solubility, waste chemicals in the form of nonaqueous phase
      liquids (NAPLs) that are entrapped in subsurface formations act as long-term
      sources of groundwater contamination. In the design of remediation schemes that
      use surfactants, it is necessary to estimate the mass transfer rate coefficients
      under multi-dimensional flow fields that exit at field sites. In this study, we
      investigate mass transfer under a two-dimensional flow field to obtain an
      understanding of the basic mechanisms of surfactant-enhanced dissolution and to
      quantify the mass transfer rates. Enhanced dissolution experiments in a two
      dimensional test cell were conducted to measure rates of mass depletion from
      entrapped NAPLs to a flowing aqueous phase containing a surfactant. In situ
      measurement of transient saturation changes using a gamma attenuation system
      revealed dissolution patterns that are affected by the dimensionality of the
      groundwater flow field. Numerical modeling of local flow fields that changed with
      time, due to depletion of NAPL sources, enabled the examination of the basic
      mechanisms of NAPL dissolution in complex groundwater systems. Through nonlinear
      regression analysis, mass transfer rates were correlated to porous media
      properties, NAPL saturation and aqueous phase velocity. Results from the
      experiments and numerical analyses were used to identify deficiencies in existing
      methods of analysis that uses assumptions of one-dimensional flow, homogeneity of
      aquifer properties, local equilibrium and idealized transient mass transfer.

PMID- 11530928
TI  - Successive identification of biodegradation rates for multiple sequentially
      reactive contaminants in groundwater.
AB  - At the field scale, the biodegradation rate is usually estimated from analytical
      solutions to single species transport with first-order reactions, using measured
      data as input. Because many contaminants, e.g., chlorinated solvents, are
      degraded in a sequential pattern, with degradation products further reacting to
      produce new species, it is of great interest to quantify the transformation rate
      of every reaction. The conventional inverse solutions for identifying the
      transformation rates are limited to single species problems. In the present
      study, we propose a successive optimization approach to identify the
      biodegradation rate for each species by using a previously developed analytical
      solution to multi-species first-order reactive transport using data obtained at
      the field scale. By specifying a link between analytical solutions to
      sequentially reactive transport problems and optimization methods and assuming
      constant transport parameters (velocity, dispersivities, and retardation
      factors), the first-order transformation rates are optimized successively from
      parent species to its daughter species.

PMID- 11530929
TI  - Modeling hydrocarbon biodegradation in tidal aquifers with water-saturation and
      heat inhibition effects.
AB  - A model is developed for hydrocarbon biodegradation, which includes saturated and
      unsaturated flow, multi-species transport, heat transport, and bacterial growth
      processes. Numerical accuracy of the model was tested against analytical
      solutions. The model was also verified against laboratory results for a saturated
      flow problem and reasonable match was obtained. Expressions are proposed for
      inhibition due to water content and temperature fluctuations. Bioactivities under
      cyclic water content variation were studied under no-flow conditions. A
      quantitative approach was used to reconcile some of the apparent contradictory
      conclusions regarding the efficiency of biodegradation of soils under wetting and
      drying conditions. The efficiency depends on the nature of the oxygenation
      process. For cases involving the presence of dissolved oxygen and the absence of
      O2 vapor, subjecting the soil to constant water content close to its optimal
      value for degradation is most efficient. However, wetting and drying can enhance
      degradation if O2 is only provided through aeration or direct contact between air
      and the medium. Also presented are the results of a typical field application of
      the model and a discussion of the effects of tides, saturation inhibition, and
      heat inhibition. Other inhibition factors, such as pH or salinity, can be easily
      incorporated in the formulation. The quantitative approach developed here can be
      used in assessing bioremediation not only in tidal aquifers but also in areas
      where water-table or temperature effects are of significance. The approach can be
      useful in the design of remediation strategies under water-flow or no-flow
      conditions involving water content and temperature fluctuations.

PMID- 11530930
TI  - On the characterization of the putative S20-thx operon of Thermus thermophilus.
AB  - A putative operon of the ribosomal proteins S20 and Thx has been determined in a
      1.4 kb sequenced region of T. thermophilus genomic DNA. Both genes have a
      promoter sequence 29 nt upstream of ORF1, possess their own Shine-Dalgarno motifs
      (GGAG) and are separated by only 9 nucleotides, a feature characteristic of the
      compact Thermus thermophilus genome. This is a novel arrangement, since Thx is
      unique to the Thermus bacteria and in all other prokaryotes the S20 gene is
      monocistronic. Our results, in conjunction with the recent finding that Thx is
      located on the top of the head of the 30S subunit in a cavity between multiple
      RNA elements stabilizing them with its positive charge, corroborate the
      observation that thermophilic ribosomes require constituents with special
      features for their stabilization at high temperatures.

PMID- 11530931
TI  - RNase-stable RNA: conformational parameters of the nucleic acid backbone for
      binding to RNase T1.
AB  - An RNA sequence showing high stability with respect to digestion by ribonuclease
      T1 (RNase T1) was isolated by in vitro selection from an RNA library. Although
      ribonuclease T1 cleaves single-stranded RNA specifically after guanosine
      residues, secondary structure calculations predict several guanosines in single
      stranded areas. Two of these guanosines are part of a GGCA-tetraloop, a recurring
      structure element in the secondary structure predictions. Molecular dynamics
      simulations of the conformation space of the nucleotides involved in this
      tetraloop show on the one hand that the nucleic acid backbone of the guanosines
      cannot realise the conformation required for cleavage by RNase T1. On the other
      hand, it could be shown that an RNA molecule not forced into a tetraloop occupies
      this conformation several times in the course of the simulation. The simulations
      confirm the GGCA-tetraloop as an RNase-stable secondary structure element. Our
      results show that, besides the known prerequisite of a single-stranded RNA, RNase
      T1 has additional demands on the substrate conformation.

PMID- 11530932
TI  - Enhanced gamma-glutamyl transpeptidase expression and superoxide production in
      Mpv17-/- glomerulosclerosis mice.
AB  - Recently, gamma-glutamyl transpeptidase, which initiates cleavage of
      extracellular glutathione, has been shown to promote oxidative damage to cells.
      Here we examined a murine disease model of glomerulosclerosis, involving loss of
      the Mpv17 gene coding for a peroxisomal protein. In Mpv17-/- cells, enzyme
      activity and mRNA expression (examined by quantitative RT-PCR) of membrane-bound
      gamma-glutamyl transpeptidase were increased, while plasma glutathione peroxidase
      and superoxide dismutase levels were lowered. Superoxide anion production in
      these cells was increased as documented by electron spin resonance spectroscopy.
      In the presence of Mn(III)tetrakis(4-benzoic acid)porphyrin, the activities of
      gamma-glutamyl transpeptidase and plasma glutathione peroxidase were unchanged,
      suggesting a relationship between enzyme expression and the amount of reactive
      oxygen species. Inhibition of gamma-glutamyl transpeptidase by acivicin reverted
      the lowered plasma glutathione peroxidase and superoxide dismutase activities,
      indicating reciprocal control of gene expression for these enzymes.

PMID- 11530933
TI  - Juvenile hormone binding protein and transferrin from Galleria mellonella share a
      similar structural motif.
AB  - It has been previously suggested that juvenile hormone binding protein(s) (JHBP)
      belongs to a new class of proteins. In the search for other protein(s) that may
      contain structural motifs similar to those found in JHBP, hemolymph from Galleria
      mellonella (Lepidoptera) was chromatographed over a Sephadex G-200 column and
      resulting fractions were subjected to SDS-PAGE, transferred onto nitrocellulose
      membrane and scanned with a monoclonal antibody, mAb 104, against hemolymph JHBP.
      Two proteins yielded a positive reaction with mAb 104, one corresponding to JHBP
      and the second corresponding to a transferrin, as judged from N-terminal amino
      acid sequencing staining. Transferrin was purified to about 80% homogeneity using
      a two-step procedure including Sephadex G-200 gel filtration and HPLC MonoQ
      column chromatography. Panning of a random peptide display library and analysis
      with immobilized synthetic peptides were applied for finding a common epitope
      present in JHBP and the transferrin molecule. The postulated epitope motif
      recognized by mAb 104 in the JHBP sequence is RDTKAVN, and is localized at
      position 82-88.

PMID- 11530934
TI  - Analysis of structural signals conferring localisation of pig OST48 to the
      endoplasmic reticulum.
AB  - Pig liver oligosaccharyltransferase (OST) is a heterooligomeric protein complex
      responsible for the co-translational transfer of GlcNAc2-Man9-Glc3 from Dol-PP
      onto specific asparagine residues in the nascent polypeptide. OST48, one of the
      catalytic subunits in this complex, exerts a typical type I membrane topology,
      containing a large luminal domain, a hydrophobic transmembrane domain and a short
      cytosolic peptide tail. Because OST48 is found within the endoplasmic reticulum
      (ER) when overexpressed in COS-1 cells, we carried out experiments to identify
      structural signals potentially capable of directing ER-targeting, using OST48
      mutants and hybrid proteins consisting of individual OST48 domains and Man9
      mannosidase. Immunofluorescence microscopy showed that OST48 mutants in which the
      C-terminal lysine-3 or lysine-5, but not lysine-7, had been replaced by leucine
      (OST48AK) could be detected on the cell surface. This indicates that these two
      lysine residues are sufficient for conferring ER-residency on OST48. The double
      lysine motif operates only when exposed cytosolically, where it acts as a
      relocation signal rather than causing retention. OST48AK-3, when co-expressed in
      COS-1 cells together with myc-tagged ribophorin 1, was quantitatively retained in
      the ER. By contrast, co-expression in the presence of ribophorin I resulted in no
      reduction of cell surface fluorescence for the OMOdeltaK-5 chimera containing the
      cytosolic and transmembrane domain of OST48 attached to the C-terminus of the
      Man9-mannosidase luminal domain. Thus ER-localisation of OST48 is probably
      brought about by complex formation with ribophorin I and this most likely
      involves the luminal domains of both proteins. Consequently, the double-lysine
      motif in the cytosolic domain of OST48 is unlikely to have a primary function
      except being involved in re-capture of molecules which have escaped from the ER.

PMID- 11530935
TI  - Identification and crystallisation of a heat- and protease-stable fragment of the
      bacteriophage T4 short tail fibre.
AB  - Irreversible binding of T-even bacteriophages to Escherichia coli is mediated by
      the short tail fibres, which serve as inextensible stays during DNA injection.
      Short tail fibres are exceptionally stable elongated trimers of gene product 12
      (gp12), a 56 kDa protein. The N-terminal region of gp12 is important for phage
      attachment, the central region forms a long shaft, while a C-terminal globular
      region is implicated in binding to the bacterial lipopolysaccharide core. When
      gp12 was treated with stoichiometric amounts of trypsin or chymotrypsin at 37
      degrees C, an N-terminally shortened fragment of 52 kDa resulted. If the protein
      was incubated at 56 degrees C before trypsin treatment at 37 degrees C, we
      obtained a stable trimeric fragment of 3 x 33 kDa lacking residues from both the
      N- and C-termini. Apparently, the protein unfolds partially at 56 degrees C,
      thereby exposing protease-sensitive sites in the C-terminal region and extra
      sites in the N-terminal region. Well-diffracting crystals of this fragment could
      be grown. Our results indicate that gp12 carries a stable central region,
      consisting of the C-terminal part of the shaft and the attached N-terminal half
      of the globular region. Implications for structure determination of the gp12
      protein and its folding are discussed.

PMID- 11530936
TI  - Toward understanding the role of insulin alpha-helix II in the growth-promoting
      activity of insulin.
AB  - For further understanding the contribution of the alpha-helix II (alphaII) in the
      growth-promoting activity of insulin, the residues A2Ile, A5Gln, and A8Thr
      located in alphaII were mutated to Leu, Glu, and Tyr, respectively. Three mutant
      insulins, [A2Leu]human insulin, [A5Glu]human insulin, and [A8Tyr]human insulin,
      were prepared by means of site-directed mutagenesis. The in vitro growth
      promoting activities of the three mutant insulins, measured using GR2H6 cells,
      were 7.5%, 291%, and 250% of that of native insulin, respectively. Their receptor
      binding activities to the insulin receptor were 2.3%, 46.7%, and 138.7%,
      respectively, compared with native insulin. Both the growth-promoting and
      receptor-binding activities of [A2Leu]human insulin and [A3Leu]insulin (Shi et
      al., 1997) were parallel and greatly decreased compared with native insulin. The
      results demonstrate that the residues A2Ile and A3Val in the alphaII are
      essential for the growth-promoting activity of insulin, and the growth-promoting
      function of insulin might be performed through, or mainly through, binding to the
      insulin receptor. The growth-promoting activities of [A5Glu]human insulin and
      [A8Tyr]human insulin were increased 6-fold and 2-fold, respectively, compared
      with native insulin, indicating that their growth-promoting activities might be
      expressed by, or mainly by, binding to the IGF-1 receptor.

PMID- 11530937
TI  - Insulin resistance induced by loop diuretics and hyperosmolarity in perfused rat
      liver.
AB  - Insulin-induced cell swelling was recently suggested to reflect an independent
      signal for metabolic insulin effects such as inhibition of hepatic proteolysis,
      which is transmitted at the level of autophagosome formation via p38MAPK
      activation [Haussinger et al., Gastroenterology 116 (1999), 921-935]. Here, the
      role of insulin-induced cell swelling in the overall context of insulin
      signalling towards proteolysis inhibition was studied in perfused rat liver. Loop
      diuretics and hyperosmolarity, which impair insulin-stimulated cell swelling,
      strongly blunt Erk-2 and p38MAPK activation as well as proteolysis inhibition by
      insulin, but are without effect on insulin-induced tyrosine phosphorylation of IR
      beta and IRS-1. Inhibitors of phosphatidylinositol-3-kinase (PI3-kinase) also
      block insulin-induced cell swelling, MAP kinase activation and proteolysis
      inhibition, but the antiproteolytic response to hypoosmolarity remains
      unaffected. We suggest that PI3-kinase-mediated cell swelling induced by insulin
      is required to amplify the insulin signal to MAP kinases and thus proteolysis
      regulation. The perturbation of insulin-induced cell swelling may be of
      pathophysiological relevance for the development of insulin resistance in
      clinical situations associated with hyperosmotic dehydration and loop diuretic
      treatment.

PMID- 11530938
TI  - Singlet molecular oxygen triggers the soxRS regulon of Escherichia coli.
AB  - The electronically excited molecular oxygen (singlet oxygen, 1O2) can be
      detrimental to cells in several ways, although recent reports indicate that it
      may play a role as an intercellular signal in eukaryotes. Here we present
      evidence that 1O2, generated by thermodissociation of disodium 3,3'-(1,4
      naphthylidene) diproprionate endoperoxide, activates transcription of genes of
      the soxRS regulon, and that this induction is paralleled by induction of a
      soxS'::lacZ operon fusion. The inductions were dependent on a functional soxR
      gene. These data imply that protective responses, such as induction of the soxRS
      regulon, may be triggered by diverse environmental oxidative stresses, and that
      1O2 may also function as a signal molecule in prokaryotes.

PMID- 11530939
TI  - The extracellular signal-regulated protein kinases Erk1/Erk2 stimulate expression
      and biological activity of the transcriptional regulator Egr-1.
AB  - The zinc finger protein early growth response 1 (Egr-1) is a transcriptional
      activator involved in the regulation of growth and differentiation. We show here
      that a constitutive active mutant of mitogen-activated kinase kinase-1 (MAPKK-1)
      strongly stimulates the activity of the Egr-1 promoter, thus explaining the
      effects of mitogens upon Egr-1 mRNA and protein levels. Moreover, we show that a
      constitutive active MAPKK-1 leads to an increase in the biological activity of
      Egr-1 to activate transcription. We conclude that the signaling pathway involving
      mitogen-activated protein kinase/extracellular signal-regulated protein kinase
      has a dual impact on the biology of Egr-1 by controlling the transcription of the
      Egr-1 gene and the transcriptional activity of the Egr-1 protein.

PMID- 11530940
TI  - The FIRE3-mediated sterol response of the FAS promoter requires NF-Y/CBF as a
      coactivator.
AB  - The transcription of the fatty acid synthase (FAS) gene is regulated by the
      sterol status of the cell via cleavage of the sterol regulatory element-binding
      protein (SREBP). When human HepG2 hepatoma cells were cotransfected with an
      expression plasmid for mature SREBP-1a together with FAS promoter/reporter
      constructs significant increases in reporter activity were observed. Deletion
      analysis of the FAS promoter between -151 and -52 relative to the transcription
      start site pinpoint two cis-elements important in sterol regulation of the FAS
      gene. One element, FIRE3, between -71 and -52 can bind in vitro translated and
      transcribed SREBP-1a whereas the other element, the inverted CCAAT element ICE(
      97/-92), binds the trimeric transcription factor NF-Y/CBF as shown with rat liver
      extract and reconstituted, recombinant NF-Y. The results clearly show that the
      coactivator for SREBP-1a in this cell line is NF-Y. This finding was confirmed by
      using a dominant negative form of NF-YA, NF-YAm29, which interferes with the
      effect of ectopically expressed SREBP-1a on FAS reporter activity.

PMID- 11530941
TI  - Complement factor I is upregulated in rat hepatocytes by interleukin-6 but not by
      interferon-gamma, interleukin-1beta, or tumor necrosis factor-alpha.
AB  - Complement factor I (FI) is a regulatory serine protease of the complement system
      which cleaves three peptide bonds in the alpha-chain of C3b and two bonds in the
      alpha-chain of C4b and thus prevents the assembly of the C3 and C5 convertases.
      We have investigated the proinflammatory cytokines IL-6, IL-1beta, TNF-alpha and
      IFN-gamma for their potential role in the regulation of FI expression. Of the
      investigated cytokines, only IL-6 increased the FI-specific RT-PCR signal in
      isolated hepatocytes, in the two rat hepatoma-derived cell lines FAO and H4IIE or
      in HUVECs. Quantitative competitive RT-PCR showed an IL-6 induced upregulation of
      FI-specific mRNA by about ten-fold. These data are in accord with Northern blot
      analyses in which the FI-mRNA was upregulated by IL-6 between five- and seven
      fold. IL-6, but not IL-1beta, TNF-alpha or IFN-gamma also increased FI-protein
      levels in cell culture supernatants by about five-fold as determined by a
      semiquantitative immunoblot using a novel monoclonal antibody specific for rat
      FI.

PMID- 11530942
TI  - Isolation and characterization of a highly specific serine endopeptidase from an
      oral strain of Staphylococcus epidermidis.
AB  - Infection by Staphylococcus epidermidis, an opportunistic pathogen, has become a
      major problem due to the increased use of implanted medical devices and the
      growing number of patients who are therapeutically or infectiously
      immunosuppressed. These infections appear to proceed via modulation of the
      coagulation and complement systems. In this communication we describe the
      purification and characterization of a novel extracellular proteinase from an
      oral strain of S. epidermidis that can degrade fibrinogen, complement protein C5,
      and several other proteins. This proteinase has a strong preference for cleavage
      after glutamic acid residues, but not after aspartic acid. The S. epidermidis
      enzyme may be a multifunctional protein which not only provides this organism
      with both the ability to evade the complement defense system and to dysregulate
      the coagulation cascade, but also supplies nutrients for its growth through the
      degradation of Glu-rich proteins.

PMID- 11530943
TI  - Functional genomics in HIV-1 virus replication: protein-protein interactions as a
      basis for recruiting the host cell machinery for viral propagation.
AB  - Identification and characterization of protein-protein interactions between the
      host cell and parasites both enhance our understanding of basic cell biology and
      provide insights into central processes of parasite life cycles. Research on HIV
      1 has broadened our knowledge of the various molecular events involved. However,
      our understanding of how this virus interacts with the host cell at the level of
      protein-protein interaction is still limited. Through these interactions the
      virus is able to recruit certain cellular metabolic pathways for its replication.
      Here we summarize our current knowledge of protein-protein interactions between
      HIV-1 and host cell factors during viral replication.

PMID- 11530944
TI  - Inhibitory effect of evodiamine on aldosterone release by Zona glomerulosa cells
      in male rats.
AB  - Evodiamine is a bioactive alkaloid extracted from a Chinese herb named Wu-Chu-Yu,
      which possesses thermoregulatory, analgesic, and cardiovascular effects. Some
      studies have demonstrated that evodiamine reduces blood pressure through acting
      on endothelium and smooth muscle cells to produce a vasodilatory effect, but
      whether it affects aldosterone secretion is unclear. The purpose of this study
      was to examine the effect of evodiamine on aldosterone release in adrenal zona
      glomerulosa (ZG) cells. ZG cells were isolated from the adrenal glands of adult
      male rats and incubated with angiotensin II (Ang II, 1x10(-7) M) and 3H
      pregnenolone in the presence or absence of evodiamine (1x10(-6)-1x10(-3) M) at 37
      degrees C for one hour. The concentration of aldosterone in the media was
      measured by a radioimmunoassay. The level of radioactivity incorporated into
      aldosterone and its precursors after incubation of ZG cells with 3H-pregnenolone
      was analyzed by thin-layer chromatography. The results demonstrated that
      evodiamine decreased the basal level of and Ang II-induced release level of
      aldosterone in rat ZG cells. Administration of evodiamine also decreased the
      level of radioactivity incorporated into 3H-corticosterone and 3H-aldosterone
      following incubation of ZG cells with 3H-pregnenolone. This suggest that
      evodiamine affects aldosterone release in rat adrenal glomerulosa cells by acting
      on Ang II-associated pathway and reducing the activity of 11 beta-hydroxylase (an
      enzyme which coverts deoxycorticosterone to corticosterone) during the
      steroidogenesis of aldosterone.

PMID- 11530945
TI  - Blunted renal responses to angiotensin II infusion in lifetime captopril-treated
      spontaneously hypertensive rats.
AB  - Previously, we had found that inhibition of the renin-angiotensin system in the
      early lifespan of spontaneously hypertensive rat could prevent the development of
      hypertension in this animal model. In the present study we evaluated the
      responses of blood pressure and renal function to intracerebroventricular
      administration of angiotensin II in long-term captopril-treated spontaneously
      hypertensive rats. Spontaneously hypertensive rats had been mated and their pups
      were treated with captopril through drinking water after birth. Age-matched
      Wistar-Kyoto and spontaneously hypertensive rats drinking tap water were used as
      control groups. At 4 months of age, the basal mean arterial blood pressure of
      captopril-treated hypertensive rats was the lowest among those of controlled
      hypertensive and normotensive rats (98+/-5 vs. 160+/-4 and 126+/-4 mmHg,
      respectively). Intravenous administration of angiotensin II caused similar
      increments of blood pressure in all rat groups. However, intracerebroventricular
      administration of angiotensin II to captopril-treated hypertensive rats induced a
      significantly less increase of arterial blood pressure in comparison with other
      groups. The sensitivity of baroreflex in captopril-treated hypertensive rats was
      also the lowest among all rat groups. The basal urine flow, sodium and potassium
      excretion rates, and osmolar clearance of captopril-treated hypertensive rats
      were significantly higher than those of controlled hypertensive rats.
      Intracerebroventricular infusion of angiotensin II caused significant increases
      in urine flow, electrolytes excretion, osmolar clearance, and free water
      reabsorption rate of both normotensive and controlled hypertensive rats. However,
      the same angiotensin II treatment did not change any of the renal excretion
      indices in captopril-treated hypertensive rats. Our results suggest that lifetime
      captopril treatment can decrease the activity of the renin-angiotensin system in
      the brain of hypertensive animals, which caused increases in basal urine flow and
      excretion of electrolytes and enhanced the sensitivity of baroreflex. It is
      likely that changes in the renal and baroreflex functions underlie the prevention
      of hypertension elicited by long-term captopril treatment.

PMID- 11530946
TI  - Clomiphene, an ovulation-inducing agent, causes [Ca2+]i increases in human
      osteoblast-like cells.
AB  - The effect of clomiphene, an ovulation-inducing agent, on cytosolic free Ca2+
      levels ([Ca2+]i) in MG63 human osteosarcoma cells was explored by using fura-2 as
      a Ca2+ indicator. Clomiphene at concentrations between 5-75 microM increased
      [Ca2+]i in a concentration-dependent manner with an EC50 of 50 microM. The
      [Ca2+]i signal consisted of an initial rise and a sustained phase. Ca2+ removal
      reduced the Ca2+ signal by 40+/-10%. The [Ca2+]i increase induced by 50 microM
      clomiphene was inhibited by 80+/-5% by 10 microM nifedipine, but was insensitive
      to 50 microM La3+ or 10 microM verapamil. In Ca2+-free medium, pretreatment with
      50 microM brefeldin A (to disrupt the Golgi complex Ca2+ store), 1 microM
      thapsigargin (to inhibit the endoplasmic reticulum Ca2+ pump), and
      carbonylcyanide m-chlorophenylhydrazone (CCCP; to uncouple mitochondria)
      inhibited 51+/-3% of 50 microM clomiphene-induced Ca2+ release; conversely,
      pretreatment with 50 microM clomiphene abolished the [Ca2+]i increase induced by
      thapsigargin, CCCP, and brefeldin A. The Ca2+ release-induced by 50 pM clomiphene
      was unchanged by inhibition of phospholipase C with 2 microM 1-(6-((17beta-3
      methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione (U73122).
      Collectively, the results suggest that clomiphene increased [Ca2+]i, in
      osteoblast-like cells, by releasing intracellular Ca2+ in a phospholipase C
      independent manner and by causing nifedipine-sensitive Ca2+ influx.

PMID- 11530947
TI  - The stimulatory effect of vasoactive intestinal peptides on the cortisol
      production of guinea pig Zona fasciculata cells: an extra-ACTH regulatory model
      of the adrenocortical function.
AB  - The effect of vasoactive intestinal peptide (VIP) on cortisol production was
      studied in a primary culture enriched with guinea pig Zona Fasciculata (ZF)
      cells. In ZF cells, VIP stimulates cortisol secretion and enhances the
      steroidogenic action of ACTH. Compared to ACTH on an equal molar basis, the
      cortisol-stimulatory effect of VIP is at least 10-fold less potent. As VIP
      exhibits a wide range of biological actions with widespread distribution in the
      body, the steroidogenic action of VIP on the adrenal glands is not tissue
      specific. There are VIP receptors in ZF cells. With the aid of a VIP receptor
      antagonist, we found that ACTH and VIP mutually bind each other's receptors with
      an affinity-ranking order of ACTH > VIP receptor antagonist > VIP. VIP stimulates
      cortisol production most likely through the cyclic AMP (cAMP) signaling pathway.
      Both ACTH receptors and the VIP receptors bind VIP receptor antagonist more
      avidly than VIP, but the bindings do not lead to a consequential effect on cAMP
      production and cortisol secretion. However, the VIP receptor antagonist
      counteracted ACTH and VIP to lower both cAMP and cortisol production. In
      addition, ASIF and BNP-32, which are the proven ACTH receptor antagonists,
      reduced the cortisol-stimulatory effect of ACTH and VIP. These results suggest
      that besides ACTH, VIP be an important factor in regulating the cortisol
      secretion from the adrenal cortex at the site of ACTH receptors. In cases with
      hypercortisolemia being detected concomitantly with normal or low ACTH levels, we
      may need to investigate the influential role of VIP.

PMID- 11530948
TI  - Gastric emptying and intestinal transit of liquid and solid markers in rats with
      chronic uremia.
AB  - Gastrointestinal motor abnormalities may account for dyspeptic symptoms of
      chronic uremia patients. However, the data on gastric emptying are conflicting in
      human studies. We, therefore, assessed gastric emptying and gastrointestinal
      transit in a rat uremia model. Chronic uremia was induced by five-sixths
      nephrectomy in the rats. After 20-hour fasting, the rats were loaded with 70
      glass beads as solid markers through a gastric catheter. Two hours later, the
      stomach was exposed and the small intestine was equally divided into 10 segments.
      The glass beads in the stomach and in each intestinal segment were counted. The
      gastric emptying was expressed as the ratio of the number of glass beads in the
      small intestine to that counted from the entire gastrointestinal tract. The
      intestinal transit was assessed by analyzing the geometric center of the
      distribution of glass beads in the intestinal segments. Two conventional
      nonabsorbable markers, radioactive chromate and charcoal, were also used to
      evaluate gastric emptying and intestinal transit in the fasted state.
      Additionally, similar experiments of glass beads were performed in the fed state.
      It was found that, in the fasted state, the gastric emptying and the intestinal
      transit of liquid or solid markers were little affected by uremia. In the fed
      state, however, chronic uremia significantly decreased the intestinal transit but
      hardly affected the gastric emptying. We conclude that the postprandial
      intestinal transit, but not the gastric emptying, of solid markers may be
      decreased in the fed state by chronic uremia in a severity-dependent manner of a
      rat model, which resembles the findings in uremic patients.

PMID- 11530949
TI  - Frequency coding ability of the somatosensory thalamocortical system and its
      modulation by anesthesia depth.
AB  - The purposes of the present study were to characterize and compare the mid-tail
      cortical and thalamic somatosensory evoked potentials (SEPs), and to examine how
      the depth of the barbiturate anesthesia affected them. After the tail
      representative locations of sacrococcygeal dorsal root (S2 or S3), thalamus
      (ventroposterior lateral nucleus, VPL) and primary somatosensory cortex (SI) were
      set up for recording, the rats were infused serially with diluted sodium
      pentobarbital solution beginning from light (5 to 10 mg/kg/hr) to deep (30 to 40
      mg/kg/hr) and then stop infusion (recovery). The effects of anesthetic depth on
      SEPs were examined of dorsal root, thalamic and cortical field potentials evoked
      by mid-tail stimulation of various stimulation intensities (100 microA to 2mA,
      step 100 pA, at 2 Hz) and frequencies (0.5 to 11 Hz, step 0.5 to 1 Hz, at 3T).
      The depth of anesthesia did not affect the strength-response curves of the SEPs.
      In contrast, the depth of anesthesia differentially influenced the frequency
      following capabilities of different recording sites. Under light anesthesia,
      thalamic SEP was only significantly affected with stimulation frequencies higher
      than 8 Hz, whereas cortical SEP was significantly affected with 2 Hz or higher.
      Under deep anesthesia, thalamic SEP evoked by low frequency tail stimulation was
      not significantly changed. In contrast, cortical SEP was affected much strongly
      so that under 1 Hz stimulation, a significant difference could be observed. We
      concluded, therefore, that thalamus was only partially responsible for the
      limited frequency following capability of the SI, and that the main effect of
      pentobarbital was on the cortical level. From the data obtained, an exponentially
      decaying curve could be observed for the cortical SEP under different stimulation
      frequencies. The decay constant showed a 50% change with a change in anesthesia
      depth. We propose that the decay constant could be used as a sensitive index for
      the monitoring of anesthetic depth.

PMID- 11530950
TI  - Flextube reflectometry for localization of upper airway narrowing--a preliminary
      study in models and awake subjects.
AB  - The aim of this study was to examine an acoustic reflection method using a
      flexible tube for identifying the obstructive site of the upper airway in snorers
      and patients with obstructive sleep apnoea (OSA). As a preliminary study it was
      performed n models and subjects in the awake state. Flextube narrowing was
      produced in a model of the nose and pharynx and three blinded observers assessed
      the obstructive level. The correlation between pharyngeal narrowing assessed by
      endoscopy and by acoustic measurement during Muller manoeuvres was also examined
      in 10 OSA patients and 11 healthy non-snoring, adults. Three blinded observers
      dentified the level of 176 of 180 random cases of flextube narrowing in a
      polycarbonate model correctly The level of narrowing was always correctly
      evaluated within 1.9 mm. Pharyngeal area decrease was measured by the flextube
      method during the Muller manoeuvre but it was not closely related to the findings
      by endoscopy. In conclusion the flextube reflectometry method was able to
      demonstrate narrowng in a model of the nose and pharynx in a precise way.
      Narrowing was also observed during Muller manoeuvres. Flextube reflectometry may
      be a promising method to detect upper airway narrowing but further evaluation
      during sleep is required.

PMID- 11530951
TI  - Flextube reflectometry for determination of sites of upper airway narrowing in
      sleeping obstructive sleep apnoea patients.
AB  - The aim of this study was to examine a new technique based on sound reflections
      in a flexible tube for identifying obstructive sites of the upper airway during
      sleep. There was no significant difference between two nights in seven
      obstructive sleep apnoea (OSA) patients regarding the level distribution of
      pharyngeal narrowings, when the pharynx was divided into two segments
      (retropalatal and retrolingual). We also compared the level distribution
      determined by magnetic resonance imaging (MRI) with the level distribution found
      by flextube reflectometry in seven OSA patients. There was no significant
      difference between flextube and MRI level distributions during obstructive
      events, but due to few subjects the power of the test was limited. We found a
      statistically significant correlation between the number of flextube narrowings
      per hour of sleep and the number of obstructive apnoeas and hypopnoeas per hour
      of sleep determined by polysomnography (PSG) in 21 subjects (Spearman's
      correlation coefficient r = 0.79, P < 0.001). In conclusion, the flextube
      reflectometry system seems to be useful for level diagnosis in OSA before and
      after treatment.

PMID- 11530952
TI  - Total nitrite/nitrate in expired breath condensate of patients with asthma.
AB  - Production of nitric oxide (NO) is generally increased during inflammatory
      diseases including asthma. The eventual fate of NO is oxidation to nitrite (NO2)
      and nitrate (NO3), both of which are end-products of NO metabolism. Hydrogen
      Peroxide (H2O2) is increased in exhaled breath condensate of asthmatic subjects
      and may be used as a non-invasive marker of oxidative stress. NO has in some
      cases been shown to attenuate oxidant-induced lung injury. Total NO2/NO3
      concentration and H2O2 levels were measured in expired breath condensate in 50
      clinically stable asthmatics [all males, all atopics, mean age 22 (3) SD yrs,
      forced expiratory volume in 1 sec (FEV1) 91 (10)% predicted, PD20 to histamine
      0.262 (0.16) mg 20 on inhaled steroids, 20 smokers, all steroid-naive] and in 10
      normal, non-atopic subjects [all males, age 23 (4) yrs, FEV1 101 (14)% predicted,
      PD20 to histamine 1.3 (0.55) mg]. NO2/NO3 levels were significantly higher in
      patients with asthma than in normal subjects (1.08, 95% CI 0.86-1.3 microM vs.
      0.6; 95% CI 0.46-0.8, P < 0.001). Patients who were on inhaled steroids had
      significantly ower values compared to steroid-naive (0.71, 95% CI 0.55-0.87
      microM vs. 133, 95% CI 1-1.65 microM, P < 0.001). Similar results were observed
      between smokers and non-smokers (1.11, 95% CI 0.74-1.47 microM vs. 1.77, 95% CI
      1.1-24 microM, P < 0.0001). There was a significant positive correlation between
      NO2/NO3 levels and H2O2 concentration in expired breath condensate (r = 0.48, P <
      0.0001). No correlation was observed between NO2/NO3 levels, airway obstruction
      and bronchial hyper-reactivity as assessed by PD20 to histamine. Total NO2/NO3
      levels in expired breath condensate are raised in patients with stable asthma and
      are significantly related to oxidative stress as assessed by H2O2 concentration.
      Measurement of expired breath NO2/NO3 and H2O2 levels may be clinically useful in
      the management of oxidation and inflammation mediated lung injury.

PMID- 11530953
TI  - The clinical utility of arterialized earlobe capillary blood in the assessment of
      patients for long-term oxygen therapy.
AB  - The prescription of long-term oxygen (LTOT) is underpinned by the measurement of
      arterial PO2, generally obtained by radial artery puncture. This test is commonly
      associated with patient discomfort and a test that is reliable, well-tolerated
      and non-invasive would be advantageous. Cutaneous oximetry has not proved
      sufficiently accurate. Arterialized earlobe capillary sampling has been proposed,
      with some authors stating that it is under-utilized. However, to date studies
      have yielded conflicting results and the clinical utility remains uncertain. Our
      regional oxygen service based at a specialist respiratory hospital undertook a
      prospective study of consecutive patients with chronic respiratory disease
      undergoing assessment for LTOT. Simultaneous radial artery and arterialized
      earlobe sampling was performed. Rigorous steps were taken to ensure optimal
      arterialization of the earlobe samples. Agreement between arterial and
      arterialized PO2 and PCO2 was compared using the Bland-Altman method. One hundred
      patients were studied. Procedural difficulties (insufficient sample or air in
      sample) were similar for both procedures, however clotting occurred more
      frequently in arterialized earlobe samples. Sixty-four sample pairs were
      available for comparison. The bias and limits of agreement between arterialized
      and arterial PO2 were wide, mean (+/- 2 SD), -048 (-2.05-1.09) kPa. The bias and
      limits of agreement for PCO2 were smaller. Using the absolute criterion (arterial
      PO2 < 7.3 kPa), 9/55 (16%) patients would receive oxygen inappropriately based on
      the arterialized earlobe sample. Conversely, no patients would have been denied
      LTOT. Radial artery puncture gave rise to significantly greater discomfort (P <
      0.0001) and level of concern (P < 0.0001). Patient preference strongly favoured
      arterialized earlobe sampling. However, despite rigorous attention to
      arterialization earlobe sampling was insufficiently accurate to replace radial
      artery puncture in the prescription of LTOT.

PMID- 11530954
TI  - Independent risk of mechanical ventilation for AIDS-related Pneumocystis carinii
      pneumonia associated with bronchoalveolar lavage neutrophilia.
AB  - The use of mechanical ventilation (MV) for AIDS-related Pneumocystis carinii
      pneumonia (PCP) has varied over time. The introduction of adjunctive
      corticosteroid therapy has changed the pathophysiology of PCP. In the present
      study, we attempted to identify factors predictive of severe respiratory failure
      requiring MV amongst patients with PCP treated in the era of adjunctive
      corticosteroid therapy. Furthermore, we studied factors associated with survival
      in relation to MV. Of 170 consecutive patients with AIDS-related PCP, 18 (11%)
      required MV. Thirteen of 18 ventilated patients died (72%). In a logistic
      regression analysis, higher age, increased bronchoalveolar lavage (BAL)
      neutrophilia and a positive BAL cytomegalovirus CMV culture were associated with
      the need of MV. In multivariate analyses, only BAL neutrophilia remained
      independently predictive of mechanical ventilation. In conclusion, short-term
      mortality remained high after the introduction of adjunctive corticosteroid
      therapy. BAL neutrophilia may be a useful prognostic marker to identify patients
      at high risk of requiring mechanical ventilation.

PMID- 11530955
TI  - The value of Ca 125 in the evaluation of tuberculosis activity.
AB  - The aim of the present study was to investigate the value of Ca 125, a tumour
      marker, in evaluation of pulmonary tuberculosis activity. This study included 96
      subjects who were divided into three groups. Group 1 consisted of 40 patients
      with active pulmonary tuberculosis. Group 2 included 20 patients with inactive
      pulmonary tuberculosis. There were 36 healthy subjects in group 3. While
      measurement of serum Ca 125 level was performed only once in groups 2 and 3, Ca
      125 levels were measured five times in group 1. The measurements were performed
      before the treatment, at the second, fourth and sixth months and the third year
      following the end of the treatment. Mean +/- SD serum Ca 125 concentrations were
      109.7 +/- 86.9 U ml(-1) in group 1, 14.5 +/- 7.8 U ml(-1) in group 2 and 10.5 +/-
      7.3 U ml(-1) in group 3. Serum Ca 125 levels were significantly higher in group 1
      than in the other groups (P < 0.0001), but there was no significant statistical
      difference between the values of groups 2 and 3 (P > 0.05). Ca 125 levels in
      group 1 showed a significant decrease after treatment (P < 0.0001). For
      estimation of the activity of tuberculosis, the sensitivity and specificity of Ca
      125 were found 97.5% and 100%, respectively at a 31 U ml(-1) cut-off point. Our
      results suggest that Ca 125 is beneficial in the determinaton of tuberculosis
      activity and in differentiation between active and inactive pulmonary
      tuberculosis.

PMID- 11530956
TI  - Eosinophil cationic protein (ECP) in saliva: a new marker of disease activity in
      bronchial asthma.
AB  - Eosinophil cells play a crucial role in the pathogenesis of asthma, and
      concentration of eosinophil cationic protein (ECP) in serum has been used to
      monitor activity of the disease. Our aim was to determine the feasibility and
      usefulness of measuring ECP in saliva and to use it as a marker of the disease.
      Thirty-eight patients with asthma and 16 healthy volunteers were included in this
      study. Repeatability of measurements of ECP in saliva was acceptable [intra-class
      correlation coefficients (Ri) = 0.74 and coefficients of repeatability (CR) =
      0.37 in five healthy subjects]. Levels of ECP in saliva were higher in asthmatics
      than in volunteers (P < 0.01). There was a significant inverse association
      between a surrogate variable reflecting disease activity (i.e. change over a few
      weeks in dose of inhaled corticosteroid required by a change in clinical status
      of asthma) and a change over the same time period in salivary ECP in 19 patients
      with stable asthma (r = -0.64, P = 0.02). Our findings indicate that levels of
      salivary ECP are elevated in patients with asthma and associated with presumed
      activity of disease as recorded by alteration of taken dose of inhaled
      corticosteroid.

PMID- 11530957
TI  - Effects on diffusing capacity and ventilation--perfusion relationships of
      budesonide inhalations for 2 months in chronic obstructive pulmonary disease
      (COPD).
AB  - Forced expiratory volumes are reduced in chronic obstructive pulmonary disease
      (COPD), mainly as a result of inflammatory and morphological changes in the small
      airways (with a diameter < 2 mm) and in the alveoli. However, it is difficult to
      detect minor changes in small airways by spirometry measurements. To study the
      effects on small airways of inhaled corticosteroids (ICS), 19 stable COPD
      patients were investigated; 15 were evaluated by ventilation-perfusion (V(A)/Q)
      relationships, assessed by the multiple inert gas elimination technique, and by
      diffusing capacity for carbon monoxide (DL(CO)), assessed by the single breath
      technique. Measurements were repeated after 2 months of budesonide inhalations
      (800 microg) twice daily. Before ICS treatment: mean forced expiratory volume in
      1 sec (FEV1) as a percentage of predicted (% P) was 40.1 (+/- 16.0)%, DL(CO)% P
      was 45.7 (+/- 25.0)% and 6.0 (+/- 6.4)% of the ventilation was directed at high
      V(A)/Q areas. The mean of the V(A)/Q ratio for ventilation (V-mean) was 2.7 times
      higher than normal. After 2 months of ICS: the mean of DL(CO)% P increased by 8.6
      (+/- 19.4)%, and FEV1/vital capacity decreased by 6.9 (+/- 11.3)%. Basal morning
      and ACTH-stimulated S-cortisol levels were significantly reduced. All the V(A)/Q
      relationships remained unchanged. In conclusion, a significant increase in
      diffusion capacity for carbon monoxide levels after treatment with corticosteroid
      inhalations for 2 months was shown, but no significant improvements were found in
      forced expiratory airflow, lung volumes, or V(A)/Q relationships.

PMID- 11530958
TI  - Incidence of physician-diagnosed asthma in adults--a real incidence or a result
      of increased awareness? Report from The Obstructive Lung Disease in Northern
      Sweden Studies.
AB  - Only limited data are available about the incidence of asthma based on
      longitudinal prospective studies. Further, the results from different studies on
      incidence vary considerably depending on the age composition of the cohorts under
      study, the used methods and the criteria for disease. Also among adults high
      incidence rates have been reported during recent years. The aim of this study was
      to examine to what extent the incidence of physician-diagnosed asthma could be
      explained by a real incidence of the disease, and to what extend by an increased
      diagnostic activity or altered diagnostic praxis. Another aim was to study risk
      factors for asthma based on incident cases. Three cross-sectional surveys have
      been performed in the same population sample living in the northern-most province
      of Sweden, Norrbotten. The first survey was performed in 1986, and 5698 subjects,
      86% of those invited, responded to a postal questionnaire. Of these, 4754
      subjects (83%) participated at the third survey in 1996. After exclusion of all
      subjects who had reported that they had asthma in 1986, or had been classified as
      having asthma in 1986, 68 men and 98 women (P=0.02) reported in 1996 that they
      had been diagnosed as having asthma by a physician. Thus, the cumulative
      incidence for the 10-year period was 3.2% among men and 4.5% among women. After
      correction for subjects who already in 1986 had reported symptoms common in
      asthma, or had been classified as having chronic bronchitis, 97 subjects with
      incident asthma remained, which corresponded to an annual incidence rate among
      men of 1.7 and among women of 2.9/1000 persons year(-1) (P=0.1). Clinical
      examinations confirmed asthma in a large majority of these 97 subjects.
      Significant risk factors were family history of asthma, both ex- and current
      smoking, and female sex. The socio-economic groups manual workers and assistant
      non-manual employees were associated with incident asthma, although not
      significantly. The increasing prevalence of asthma among adults during recent 10
      20 years may to a considerable extent be explained by an increased diagnostic
      activity or altered diagnostic praxis. Use of different methods when measuring
      incidence may in part explain the extremely diverging incidence rates of asthma
      found in different studies.

PMID- 11530959
TI  - Prevalence of daytime hypercapnia or hypoxia in patients with OSAS and normal
      lung function.
AB  - The purpose of this study was to determine factors increasing daytime PaCO2 or
      PaO2 in obstructive sleep apnoea syndrome patients (OSAS) with normal pulmonary
      function tests. Anthropometric, pulmonary function tests, arterial blood gases
      and sleep polygraphic data were analysed retrospectively in 218 OSAS patients
      (apnoea-hypopnoea index > 15 h(-1); 18 females, 55 +/- 11 years): 125 patients
      had abnormal pulmonary function tests, i.e. one or more flow or volume under 80%
      or above 120% of predictive value (group I) and 93 had normal pulmonary function
      tests (group II). Hypercapnia was defined as PaCO2 > or = 6.0 kPa and hypoxia as
      PaO2 < 9.3 kPa. Patients with abnormal pulmonary function tests were more hypoxic
      and hypercapnic, more obese, and had a higher apnoea-hypopnoea index (P<0.05).
      Seventeen patients of group I and four of group II were hypercapnic (13.6% and
      4.3%, respectively). Thirty-one patients in group I (24.8%) had a PaO2 < 9.3 kPa
      and six (6.5%) in group II. Stepwise multiple regression analysis showed that in
      group II, only two factors were correlated with PaCO2: mean apnoea duration and
      FRC (respectively: c=0.228, P<0.001; c=0.006, P=0.108); and only two with PaO2:
      mean apnoea duration: (c=-0.218, P=0.029) and BMI (c=-3.72, P<0.0001). Daytime
      hypercapnia is present in 4.3% and daytime hypoxia in 6.5% of patients with
      occlusive sleep apnoea syndrome and normal pulmonary function tests. These
      alterations in blood gases in OSAS with normal pulmonary function tests should be
      considered as OSAS severity criteria.

PMID- 11530960
TI  - Ras oncoprotein expression in erionite- and asbestos-induced Turkish malignant
      pleural mesothelioma patients--a pilot study.

PMID- 11530961
TI  - Genetic factors associated with endothelial dysfunction affect the early onset of
      coronary artery disease in Korean males.
AB  - The maintenance of balance between nitric oxide (NO) and the superoxide anion is
      required for proper functioning of the endothelium. To investigate the
      relationship between genetic factors associated with endothelial function and the
      development of coronary artery disease (CAD), endothelial nitric oxide synthase
      (ecNOS) gene a/b polymorphism and NADH/NADPH oxidase p22 phox gene C242T
      polymorphism were examined in 305 Korean male CAD patients and 215 healthy male
      control subjects. The beta-fibrinogen gene H1/H2 polymorphism was also analyzed.
      Both ecNOS a/b and p22 phox C242T polymorphisms were found to be associated with
      the development of CAD in the study population (p=0.020 and 0.011, respectively).
      When the association was analyzed by age, statistical significance was retained
      only in those <51 years (p=0.021 and 0.025 for the a/b and the C242T
      polymorphism, respectively) and not in those >51 years of age (p=0.155 and 0.278
      respectively). However, the distribution of the beta-fibrinogen H1/H2 genotypes
      was not found to be associated with the development of CAD in either the < or =50
      (p = 0.611) or >50 groups (p = 0.188). The ecNOS gene a/b polymorphism and the
      NADH/NADPH oxidase p22 phox gene C242T polymorphism were found to be
      significantly associated with the development of CAD in Korean male patients less
      than 51 years old.

PMID- 11530962
TI  - Transcatheter embolization of renal artery aneurysm in Behcet's disease.
AB  - A 20-year-old man with Behcet's disease presented with a ruptured renal artery
      aneurysm. This patient had previously had aneurysms of the coronary arteries and
      coronary vein thrombosis that were treated with immunosuppression. A selective
      transcatheter embolization of the renal artery branch was done successfully and
      treatment with corticosteroids and methotrexate was added. Presented here is a
      rare complication of Behcet's disease, with discussion on the pathophysiology,
      differential diagnosis, and the advantages and disadvantages of the angiographic
      treatment. This paper is supplemented with a comprehensive review of the
      literature.

PMID- 11530963
TI  - Heparin-induced thrombocytopenia: natural history, diagnosis, and management.
AB  - Heparin-induced thrombocytopenia (HIT) is an under-recognized, limb- and life
      threatening complication of pharmacologic heparin administration. Antibody
      formation against heparin complexed to platelet factor 4 (PF4) is central to the
      pathogenesis of HIT. Heparin:PF4 antibodies promote platelet activation and
      aggregation as well as excess thrombin generation which may lead to clinical
      thrombosis. HIT should be suspected in patients who develop thrombocytopenia with
      or without associated arterial or venous thrombosis while on heparin. HIT is a
      clinical diagnosis. Specialized HIT assays should be interpreted with care. The
      cornerstone of HIT management is the discontinuation of all forms of heparin
      exposure and the institution of anticoagulation with an alternative agent. The
      direct thrombin inhibitors lepirudin and argatroban are currently available and
      approved for use in patients with HIT.

PMID- 11530964
TI  - Images in vascular medicine. Hypothenar hammer syndrome.

PMID- 11530965
TI  - Images in vascular medicine. Complications of retroperitoneal fibrosis.

PMID- 11530967
TI  - Inpatient utilization of medical services associated with peripheral arterial
      disease-related inpatient procedures in the Department of Defense.
AB  - The objective of this study was to describe the inpatient procedural medical care
      utilization the first 10 years after initial inpatient confirmation of peripheral
      arterial disease (PAD). A retrospective review was carried out of the computer
      records of all the army beneficiaries of the Department of Defense healthcare
      system since 1971. Over 8000 subjects with an initial inpatient confirmation of
      PAD between January 1, 1980 and December 31, 1985 were reviewed for 10 years
      following the initial visit. The utilization of PAD-related invasive procedures
      gradually increased over the first 8 years, and rose sharply in the ninth and
      tenth years after initial diagnosis, while the utilization of examination
      procedures was highest in the first, fifth to seventh, ninth and tenth years.
      Procedures involving bypass and amputation had the highest utilization among
      invasive procedures, while procedures involving arteriography and ultrasonography
      accounted for 88% of all examination procedures. Bypass and repair of vessel
      procedures gradually rose throughout the 10 years after initial diagnosis, while
      amputations and skin grafts remained relatively constant. Procedures involving
      arteriography rose until year 5 and then tapered off, while utilization of
      ultrasonography rose in year 7 and tapered off. These results suggest that PAD
      related studies should consider the progression of the disease past the fifth
      year after the initial inpatient visit for PAD when measuring a change in
      outcomes.

PMID- 11530968
TI  - Claudication does not always precede critical leg ischemia.
AB  - Prevalence of intermittent claudication is often used to calculate the prevalence
      of critical leg ischemia (CLI), a more severe form of peripheral arterial disease
      (PAD). Although this logical course of the disease is intellectually appealing,
      not all patients with CLI have experienced any symptoms of previous claudication.
      A total of 100 consecutive patients with objective evidence of critical ischemia,
      as evaluated by non-invasive testing in the authors' vascular laboratory, were
      subjected to a structured interview to evaluate how often peripheral arterial
      disease is presented with symptoms of CLI as the initial complaint. In all, 37
      patients had never experienced claudication prior to the development of CLI.
      Furthermore, 12 of 63 patients who suffered from previous claudication did not
      have any claudication symptoms at the time of the development of CLI. Of the 37
      patients with CLI as the first sign of PAD, 20 had diabetes--four of whom with
      manifest diagnosed neuropathy. The patients without previous claudication more
      frequently had ulcers as the initial symptom of CLI (89%) than those with
      claudication (59%), whose disease first progressed to rest pain. Altogether, 25
      patients did not walk enough to develop symptoms of claudication. In conclusion,
      every patient presenting with symptoms potentially related to CLI should undergo
      vascular laboratory measurements regardless of whether he/she has a history of
      claudication or not. This is especially true in limbs with unhealed skin lesions.

PMID- 11530969
TI  - Predictors of carotid endarterectomy in middle-aged individuals.
AB  - The objective was to investigate which screening variables in a population study
      predicted carotid endarterectomy. Among 793 carotid endarterectomies performed at
      Malmo University Hospital between 1991 and 1998, 85 patients (14 females) were
      identified that had participated in a population screening between 1974 and 1991.
      Median time from screening to operation was 16 years (range 6-26 years).
      Screening variables were compared with corresponding values from the background
      screening population (n = 33261). As operated patients were older than the
      background population at screening (49 [37-60] vs. 46 [26-61] years; p < 0.0001),
      comparisons were age-adjusted. Operated patients had higher systolic blood
      pressure (SBP; 130 [126-133] vs. 125 [125-125] mmHg; p < 0.01), serum total
      cholesterol (6.1 [5.9-6.3] vs. 5.7 [5.7-5.7] mmol/l; p < 0.0001), serum
      triglyceride (1.4 [1.3-1.6] vs. 1.1 [1.1-1.1] mmol/l; p < 0.0001), serum glutamic
      acid transferase (0.46 [0.40-0.53] vs. 0.40 [0.40-0.41] microkat/l; p < 0.05),
      and plasma fibrinogen (3.77 [3.42-4.16] vs. 3.35 [3.30-3.41] mmol/l; p < 0.05)
      levels, a lower 120-min insulin/glucose ratio at an oral glucose tolerance test
      (OGTT; 0.48 [0.38-0.58] vs. 0.60 [0.59-0.61]; p < 0.05) and forced vital lung
      capacity (3.7 [3.6-3.9] vs. 3.9 [3.9-4.0] l/min; p < 0.05), and a higher
      prevalence of smoking at screening (68% vs. 45%; p < 0.0001). Smoking, SBP, serum
      total cholesterol, and the 120-min insulin/glucose ratio remained independent
      predictors for carotid surgery in multivariate analysis. No differences existed
      among patients operated on because of symptomatic and asymptomatic stenosis. In
      conclusion, increased SBP and total cholesterol, lower 2-h insulin/glucose ratio
      at an OGTT, and smoking predict carotid surgery at long-term follow-up.

PMID- 11530970
TI  - The Minnesota Regional Peripheral Arterial Disease Screening Program: toward a
      definition of community standards of care.
AB  - The Minnesota Regional Peripheral Arterial Disease Screening Program was designed
      to define the efficacy of community PAD detection efforts, to assess the disease
      specific and health-related morbidity, to assess PAD awareness rates, and to
      determine the magnitude of atherosclerosis disease risk factors and the intensity
      of their management. The target population was recruited via mass media efforts
      directed at individuals over 50 years of age and those with leg pain with
      ambulation. Screening sessions included assessments of the ankle-brachial index,
      blood pressure, fasting lipid profile, and use of validated tools to detect
      symptomatic claudication (by the Modified WHO-Edinburgh Claudication
      Questionnaire), walking impairment (Walking Impairment Questionnaire - WIQ),
      quality of life (MOS SF-36), PAD awareness, and the intensity of PAD medical
      therapeutic interventions. PAD was defined as any ankle-brachial index < or =0.85
      or a history of lower extremity revascularization. The program evaluated 347
      individuals and identified 92 subjects with PAD and 255 subjects without PAD,
      yielding a detection rate of 26.5%. Individuals with PAD were older, tended to
      have higher blood pressures, and had a significant walking impairment and an
      impaired health-related quality of life compared with the non-PAD subjects.
      Current rates of tobacco use were low. Lipid-lowering, estrogen replacement, anti
      platelet, and antihypertensive medications and exercise therapies were
      underutilized in the PAD cohort. Peripheral arterial disease awareness was low in
      these community-identified patients. This Program demonstrated that individuals
      with PAD can be efficiently identified within the community, but that current
      standards of medical care are low. These data can assist in the future
      development of PAD awareness, education, and treatment programs.

PMID- 11530971
TI  - Diameter, pressure and compliance relationships in dorsal hand veins.
AB  - The diameter-pressure characteristics of dorsal hand veins previously have not
      been characterized. In this study, the effects of distending pressure with and
      without infused norepinephrine on diameter and compliance were observed. The
      elevation needed for venous collapse was measured, and the effects of baseline
      constriction on venous reactivity were assessed. In seven supine subjects, a
      brachial cuff on an elevated arm was used to generate distending pressures while
      a linear variable displacement transformer (LVDT) measured changes in venous
      diameter. Arctangent functions of distending pressure were fitted to the
      normalized diameter, then compliance functions were calculated. In supine
      subjects, 5-15 cm of elevation emptied dorsal hand veins. Norepinephrine
      decreased the venous diameter at any distending pressure by increasing the P50
      without significantly changing the midpoint slope. Compliance was a nearly single
      valued function of the normalized diameter with a maximum value at about 60%
      distention. Reactivity depends on distending pressure and baseline P50.
      Percentage constriction is a function of initial and final P50 and of distending
      pressure.

PMID- 11530972
TI  - Speech-motor control and interhemispheric relations in recovered and persistent
      stuttering.
AB  - The neurological basis of stuttering is associated with anomalies of
      interhemispheric relations and of the neural mechanisms of speech-motor control,
      specifically those involving the supplementary motor area (SMA). Stuttering
      typically develops through childhood and adolescence but many children will
      recover without formal treatment or intervention. The hypothesis that such
      spontaneous recovery is related to a maturation of the SMA is explored. Four
      experimental tasks were performed by adults whose stuttering has persisted,
      adults who reported having stuttered as children, and a control group of adults
      who reported never having stuttered. A Sequence Reproduction Finger Tapping task
      (Webster, 1986) and a Bimanual Crank Turning task (Preilowski, 1972) examined the
      functioning of the SMA, and 2 Divided Visual Field tasks examined asymmetries of
      hemispheric activation. The overall pattern of results for persistent stutterers
      compared to nonstutterers was consistent with motor-perceptual anomalies
      previously reported in the literature. The Bimanual Crank Turning task revealed
      additionally that the bimanual coordination deficits reported in adults who
      stutter are kinesthetically based and mediated through anterior callosal systems,
      including the SMA. Ex-stutterers were similar to nonstutterers in their
      performance of the motor control tasks, but similar to persistent stutterers in
      perceptual asymmetries associated with Divided Visual Field tasks. Taken
      together, the results from the four experimental tasks support the general
      hypothesis that an anomaly in interhemispheric relations and a deficit in the
      mechanisms of speech-motor control are each a necessary but not sufficient
      condition for stuttering and that recovery from childhood stuttering reflects a
      maturation of the mechanisms of speech-motor control.

PMID- 11530973
TI  - Mechanisms of postnatal neurobiological development: implications for human
      development.
AB  - This review focuses on the postnatal neuroanatomical changes that arise during
      the first years of human life. Development is characterized by 2 major
      organizational periods. The first period begins at conception and includes the
      major histogenetic events such as neurulation, proliferation, migration, and
      differentiation. It has been proposed that these events may be controlled by
      genetic and epigenetic events, which give rise to neural structures that are
      amenable to external influence. The second period is a time of reorganization in
      the human cortex. These events occur during gestation and continue postnatally,
      possibly through the 2nd decade of life. This stage is characterized by dendritic
      and axonal growth, synapse production, neuronal and synaptic pruning, and changes
      in neurotransmitter sensitivity. Although the initiation of these events is
      influenced by endogenous signals, further neural maturation is primarily
      influenced by exogenous signals. To illustrate both the progressive and
      regressive events during the postnatal period, we use examples from the
      development of the human cortex.

PMID- 11530974
TI  - Predictive accuracy of the wide range assessment of memory and learning in
      children with attention deficit hyperactivity disorder and reading difficulties.
AB  - The predictive accuracy of the Wide Range Assessment of Memory and Learning
      (WRAML; Sheslow & Adams, 1990) over and above more standardized diagnostic tools
      in children with attention deficit hyperactivity disorder (ADHD) and reading
      disabilities (RD) was examined. Fifty-three children with ADHD, 63 with RD, 63
      with ADHD-RD, and 112 normal comparison children were administered the WRAML, the
      Wechsler Intelligence Scale for Children-Third Edition (WISC-III; Wechsler,
      1991), the Achenbach (1991) Child Behavior Checklist (CBCL), and the Woodcock
      Johnson Psycho-Educational Battery-Revised (WJ-R; Woodcock & Johnson, 1989).
      Results of a series of discriminant function analyses revealed that the academic,
      intellectual, and behavioral measures could correctly classify 73.1% of children,
      but the WRAML subtests alone were able to correctly classify only 58.5% of
      participants. Combining all of the memory, academic, intellectual, and behavioral
      measures resulted in 77.5% of cases being correctly classified. These results
      suggest that the use of a measure of memory functioning such as the WRAML did not
      significantly improve the predictive accuracy of a diagnosis of ADHD, RD, or both
      over and above more standard diagnostic academic, intellectual, and behavioral
      measures.

PMID- 11530975
TI  - Age-related changes in regional brain activation during phonological decoding and
      printed word recognition.
AB  - Using magnetic source imaging, age-related changes in spatiotemporal brain
      activation profiles associated with printed word recognition and phonological
      decoding (pseudoword reading) were examined in 27 adults and 22 children without
      reading problems. Adults showed a distinct spatiotemporal profile during reading
      of both types of print consisting of bilateral activation of occipital cortices,
      followed by strongly left-predominant activation of basal temporal regions, and,
      finally, left hemisphere temporoparietal (including the angular gyrus) and
      inferior frontal activation. Children lacked the clear temporal distinction in
      the engagement of basal and temporoparietal areas and displayed significantly
      weaker activation of the left inferior frontal gyrus. In addition, the consistent
      hemispheric asymmetries in the degree of activation of basal temporal regions
      that were present in the adult readers were not apparent in the children. In
      contrast, the strong left hemisphere preponderance in the degree of activation of
      temporoparietal areas was present in children as well as adults, regardless of
      the type of print they were asked to read. The data suggest that the degree of
      specialization of cortical regions for reading, as well as the pattern of
      regional interactions that supports this specialization, may change with age.

PMID- 11530976
TI  - Prenatal neurobiological development: molecular mechanisms and anatomical change.
AB  - During prenatal development, the central nervous system is transformed from a
      thin layer of unspecified tissue into a complex system that can process
      information and organize actions. There are 8 general mechanisms that permit this
      transformation: neural induction, neurulation, proliferation, migration, axonal
      outgrowth, synaptogenesis, differentiation, and apoptosis. These processes as
      well as the anatomical changes they cause are described. Future research with
      humans, such as in utero MRI as well as behavioral and electrophysiological
      testing of infants following specific prenatal perturbations, is suggested to
      link the findings from molecular approaches to developmental neuropsychology.

PMID- 11530977
TI  - Quantitative analysis of the principle soy isoflavones genistein, daidzein and
      glycitein, and their primary conjugated metabolites in human plasma and urine
      using reversed-phase high-performance liquid chromatography with ultraviolet
      detection.
AB  - Soy isoflavones are becoming of increasing interest as nutritional agents which
      can be used to combat osteoporosis and hyperlipidemia, and are also being
      considered as potential cancer chemopreventive compounds. However, prior to their
      formulation and distribution as therapeutic agents, thorough pharmacokinetic and
      toxicological assessment needs to be completed in men and women in a variety of
      health conditions in order to ensure their therapeutic efficacy and safety. At
      this time, studies of purified soy isoflavones are possible, and are being
      designed to fully evaluate the pharmacological utility of these preparations. In
      support of these studies, quantitative analysis of soy isoflavones in biological
      fluids can be accomplished with a wide variety of methods and analytical
      instrumentation. However, the relatively ubiquitous presence of high-performance
      liquid chromatography with ultraviolet detection (HPLC-UV) in most analytical
      laboratories, the relative ease of its operation, and the lesser expense of this
      instrumentation as compared to more sophisticated techniques such as liquid
      chromatography-mass spectrometry, offers some distinct advantages for its use in
      pharmacokinetic studies. In this manuscript, the development and validation of an
      HPLC-UV method for the quantitation of the principal soy isoflavones, genistein,
      daidzein, and glycitein, and their primary metabolites, in human plasma and urine
      is described. This analytical approach allows for pharmacologically relevant
      concentrations of the analytes and their principle metabolites to be detected,
      and has been validated in close agreement with the US Food and Drug
      Administration's guidelines for the validation of methods to be used in support
      of pharmacokinetic studies.

PMID- 11530978
TI  - Determination of vigabatrin in human plasma and urine by high-performance liquid
      chromatography with fluorescence detection.
AB  - A sensitive and specific HPLC method has been developed for the assay of
      vigabatrin in human plasma and urine. The assay involves derivatization with 4
      chloro-7-nitrobenzofurazan, solid-phase extraction on a silica column and
      isocratic reversed-phase chromatography with fluorescence detection. Aspartam was
      used as an internal standard. The assay was linear over the concentration range
      of 0.2-20.0 microg/ml for plasma and 1.0-15.0 microg/ml for urine with a lower
      limit of detection of 0.1 microg/ml using 0.1 ml of starting volume of the
      sample. Both the within-day and day-to-day reproducibilities and accuracies were
      less than 5.46% and 1.6%, respectively. After a single oral dose of 500 mg of
      vigabatrin, the plasma concentration and the cumulative urinary excretion of the
      drug were determined.

PMID- 11530980
TI  - Reduction of extraction times in liquid-phase microextraction.
AB  - Recently, we introduced a simple and inexpensive disposable device for liquid
      phase microextraction (LPME) based on porous polypropylene hollow fibres. In the
      present paper, extraction times were significantly reduced by an increase in the
      surface of the hollow fibres. The model compounds methamphetamine and citalopram,
      were extracted from 2.5 ml of urine, plasma, and whole blood after dilution with
      water and alkalisation with 125 microl of 2 M NaOH though a porous polypropylene
      hollow fibre impregnated with hexyl ether and into an aqueous acceptor phase
      consisting of 0.1 M HCl. Two commercially available hollow fibres, which differed
      in surface area, wall thickness and internal diameter, were compared. An increase
      in the contact area of the hollow fibre with the sample solution by a factor of
      approximately two resulted in reduction in equilibrium times by approximately the
      same factor. Thus, the model compounds were extracted to equilibrium within 15
      min from both urine and plasma, and within 30 min from whole blood. For the first
      time LPME was utilised to extract drugs from whole blood, and the extracts were
      comparable with plasma both with regard to sample clean-up and extraction
      recoveries. Extraction recoveries for methamphetamine and citalopram varied from
      60 to 100% using the two fibres and the different matrices.

PMID- 11530979
TI  - Rapid high-performance liquid chromatographic measurement of venlafaxine and O
      desmethylvenlafaxine in human plasma. Application to management of acute
      intoxications.
AB  - Venlafaxine, a second-generation antidepressant, acts by inhibition of the
      reuptake of presynaptic noradrenaline and serotonin. The main metabolite, O
      desmethylvenlafaxine was found biologically active. For toxicological purpose, a
      rapid specific and accurate RP-HPLC assay was developed for the simultaneous
      determination of venlafaxine and O-desmethylvenlafaxine in human plasma. A linear
      response was observed over the concentration range 0.2-4 microg/ml. A good
      accuracy (<8%) was achieved for all quality controls, with intra-day and inter
      day variation coefficient less than 10%. Finally, no interference was observed
      with other psychotic drugs encountered in acute poisoning. This rapid method (run
      time <10 min) was used to manage four voluntary intoxications involving
      venlafaxine.

PMID- 11530981
TI  - High-performance liquid chromatographic method for simultaneous determination of
      hawthorn active components in rat plasma.
AB  - A simple HPLC method with photodiode-array (PDA) ultraviolet detection was
      developed for the simultaneous determination of four active polyphenol components
      of hawthorn (Crataegus), chlorogenic acid, epicatechin, hyperoside and
      isoquercitrin, in rat plasma. Following extraction from the plasma samples with
      ethyl acetate-methanol (2:1, v/v), these four compounds were successfully
      separated using a C18 column with a gradient elution of 5 and 25% acetonitrile in
      25 mM phosphate buffer (pH 2.4). The flow-rate was set at 1 ml/min and the eluent
      was detected at 325 nm for chlorogenic acid, 278 nm for epicatechin, and 360 nm
      for both hyperoside and isoquercitrin. Narignin (0.82 microg) was used as the
      internal standard and was detected at 278 nm. The method is linear over the
      studied range of 0.16-40, 0.63-160, 0.13-32 and 0.13-30 microg/ml for chlorogenic
      acid, epicatechin, hyperoside and isoquercitrin, respectively. The correlation
      coefficient for each analyte was greater than 0.995. The intra-day and inter-day
      precision of the analysis was better than 4 and 7%, respectively. The extraction
      recoveries at low to high concentration were greater than 85% for both
      epicatechin and chlorogenic acid, and greater than 94% for both hyperoside and
      isoquercitrin. The detection limits were 0.04, 0.20, 0.03 and 0.03 microg/ml for
      chlorogenic acid, epicatechin, hyperoside and isoquercitrin. The developed method
      was used to analyze the plasma concentrations of the four analytes after the
      intravenous administration of hawthorn polyphenol extract to rats.

PMID- 11530982
TI  - Determination of palladium in human urine by high-performance liquid
      chromatography and ultraviolet detection after ultraviolet photolysis and
      selective solid-phase extraction.
AB  - The high-performance liquid chromatographic method with UV detection described
      below permits the selective determination of traces of palladium in human urine.
      After UV photolysis, during which the complete organic matrix was destroyed, the
      palladium was selectively enriched by solid-phase extraction (SPE). The reversed
      phase C18 SPE column material was loaded with the ligand N,N-diethyl-N'
      benzoylthiourea (DEBT) which shows an excellent complexing capacity for palladium
      in acidic solutions and at room temperature. The Pd(DEBT)2 complex was eluted
      with ethanol. After isocratic separation on the analytical column (MeOH/H2O 98:2
      (v/v)), the complex was detected at 274 nm. The detection limit was 10 ng Pd/l.
      The relative standard deviations (RSD) of the within-series imprecision were in
      the range between 11% (75 ng Pd/l) and 7% (180 ng Pd/l). The between-day
      imprecision was 11% (75 ng Pd/l) and 5% (180 ng Pd/l). The recovery rates ranged
      between 94 and 96%. Using this method, urine samples of 44 persons from the
      general population were analysed. Only in one urine sample could palladium be
      detected. For comparison, 10 persons with occupational palladium exposure were
      examined. The urinary concentrations ranged from <10 to 2,538 ng/l.

PMID- 11530983
TI  - Development of a simplified, sensitive high-performance liquid chromatographic
      method using fluorescence detection to determine the concentration of UCN-01 in
      human plasma.
AB  - UCN-01 is a naturally derived anticancer agent isolated in the culture broth of
      actinomyces streptomyces. We have developed a sensitive high-performance liquid
      chromatographic method for the determination of UCN-01 in human plasma. UCN-01
      was isolated from human plasma after intravenous administration, by using 100%
      ice-cold acetonitrile liquid-liquid phase extraction. Liquid chromatographic
      separation was achieved by isocratic elution on a phenyl analytical column. The
      mobile phase consisted of acetonitrile-0.5 M ammonium acetate (45:55) with 0.2%
      triethylamine added as a modifier. The UCN-01 peak was identified from other
      peaks using fluorescence excitation energy and emission energy wavelengths of 310
      and 410 nm, respectively. Retention time for UCN-01 was 4.2 +/- 0.5 min. The UCN
      01 peak was baseline resolved, with nearest peak at 2.6 min distance. No
      interfering peaks were observed at the retention time of UCN-01. Peak area
      amounts from extracted samples were proportional over the dynamic concentration
      range used: 0.2 to 30 microg/ml. Mean recoveries of UCN-01 at concentrations of
      0.5 and 25 microg/ml were 89 and 90.2%, respectively. Relative standard
      deviations for UCN-01 calibration standards ranged from 1.89 to 2.31%, with
      relative errors ranging from 0.3 to 11.6%. Assay precision for UCN-01 based on
      quality control samples of 0.50 microg/ml was +/- 4.86% with an accuracy of +/
      5.7%. For drug extracted from plasma the lowest limit of detection was 0.1
      microg/ml, with the lowest limit of quantitation being 0.2 microg/ml. This method
      is suitable for routine analysis of UCN-01 in human plasma at concentration from
      0.2 to 30 microg/ml.

PMID- 11530984
TI  - Simultaneous quantitation of ephedrines in urine by gas chromatography-nitrogen
      phosphorus detection for doping control purposes.
AB  - A gas chromatographic method for the simultaneous quantitation of ephedrine,
      pseudoephedrine, norephedrine (phenylpropanolamine), norpseudoephedrine (cathine)
      and methylephedrine in urine is described. The method consists of a liquid-liquid
      extraction with tert.-butyl methyl ether at pH 14. The extracts are analysed on a
      GC system equipped with an Rtx-5 Amine column and a nitrogen-phosphorus detector.
      Method validation shows excellent separation, linearity, specificity, accuracy,
      precision, intra-laboratory repeatability and reproducibility, making the method
      especially suitable for quantitation of ephedrines in urine samples for doping
      control purposes. A statistical analysis on the abuse of the different ephedrines
      in urine from athletes controlled in the Flemish doping control laboratory during
      the period 1993-2000 is included.

PMID- 11530985
TI  - High-throughput fluorescence flow-injection topoisomerase II inhibition assay.
AB  - A high-throughput fluorescence flow-injection assay is described, suitable for
      determining the catalytic inhibition of DNA topoisomerase II. The method, which
      separates high molecular mass trypanosome kinetoplast DNA from its decatenated
      product by centrifugation, should be useful for the rapid and accurate screening
      of potential anticancer topoisomerase II inhibitors and the determination of
      their inhibition constants. Advantages of the flow-injection method over agarose
      gel electrophoresis and radioactive centrifugation assays are that it is faster,
      more sensitive, highly linear in its response to product formation, and does not
      require the production of radioactive trypanosome kinetoplast DNA substrate.

PMID- 11530986
TI  - Analysis of theaflavins in biological fluids using liquid chromatography
      electrospray mass spectrometry.
AB  - A HPLC-MS procedure for the sensitive and specific analysis of the black tea
      flavonoid theaflavin in human plasma and urine was developed. Levels were
      measured after enzymatic deconjugation, extraction into ethyl acetate, and
      separation by HPLC, using tandem mass spectrometry as a detecting system. Two
      healthy volunteers consumed 700 mg theaflavins, equivalent to about 30 cups of
      black tea. The maximum concentration detected in blood plasma was 1.0 microg l(
      1) in a sample collected after 2 h. The concentration in urine also peaked after
      2 h at 4.2 microg l(-1). Hence, only minute amounts of theaflavins can be
      detected in plasma and urine samples of healthy volunteers after ingestion.

PMID- 11530987
TI  - Rapid high-performance liquid chromatographic method for the separation of
      hydroxylated testosterone metabolites.
AB  - A rapid high-performance liquid chromatography (HPLC) method is described for the
      quantitation of hydroxytestosterone metabolites. The method combines a Hypersil
      BDS C18 analytical column (10 cm x 0.46 cm) and a linear mobile phase (1.25
      ml/min) gradient of tetrahydrofuran-acetonitrile-water (10:10:80, v/v) changing
      to tetrahydrofuran-acetonitrile-water (14:14:72, v/v) over 10 min then remaining
      isocratic for 3 min. The total run time for the chromatographic separation of
      eight metabolites of testosterone is 15 min. Detection by UV is linear between
      300 ng/ml and 10 microg/ml with a limit of detection on column of 300 ng/ml. A
      method for the direct HPLC analysis of liver microsomal incubates of
      [14C]testosterone is also briefly described and when combined with the HPLC
      method, offers a distinct advantage over previously reported methods for the
      rapid screening of testosterone hydroxylase activity in rat and human liver
      microsomes.

PMID- 11530988
TI  - Analysis of lycopene geometrical isomers in biological microsamples by liquid
      chromatography with coulometric array detection.
AB  - Methods of analysis for determining low quantities of lycopene cis-trans isomers
      in biological tissues are needed. Development of two liquid chromatography (LC)
      methods based on the polymeric C30 stationary phase equipped with coulometric
      electrochemical array detection (ED) is described. Separation of 13 lycopene
      isomers including prolycopene, (a novel tetra-cis-lycopene found in Tangerine
      tomatoes) was accomplished with both isocratic and gradient methods using
      different proportions of methanol, methyl tert.-butyl ether, water and 1 M
      ammonium acetate buffer. Carotenoids were detected at potential settings between
      200 and 620 mV. Differences in generated current-voltage curves aided in
      tentative identification of trans carotenoid species and select cis isomers of
      lycopene. These methods were successfully applied in the analysis of small
      quantities of plasma, buccal mucosal cells, prostate and cervical tissues. Limits
      of detection for trans-lycopene by ED were found to be 50 fmol representing a 10-
      to 100-fold increase over conventional UV-Vis absorbance methods.

PMID- 11530989
TI  - In-use stability of monoamine metabolites in human cerebrospinal fluid.
AB  - Cerebrospinal fluid (CSF) concentrations of the monoamine metabolites
      homovanillic acid (HVA) and 5-hydroxyindolacetic acid (5-HIAA) are commonly used
      to provide information about central nervous system (CNS) dopaminergic and
      serotonergic activity. However, little attention has been given to the effects of
      sample handling on the concentrations of these compounds in human CSF. Using high
      performance liquid chromatography (HPLC) with electrochemical detection, we
      observed that, in CSF stored at -80 degrees C, concentrations of the serotonin
      metabolite 5-HIAA and the dopamine metabolite HVA remained unchanged through six
      1-h and six 24-h freeze-thaw cycles. Exposure to bright room light (3 h, 1,230
      lux) resulted in a 5-HIAA concentration that was 96.3 +/- 2.0% of the initial and
      an HVA concentration that was 98.8 +/- 1.03% of initial. The pH of the CSF
      significantly increased during both freeze-thaw series and while maintained on
      ice (4 degrees C). These results demonstrate the in-use stability of 5-HIAA and
      HVA in human CSF under commonly-encountered laboratory conditions.

PMID- 11530990
TI  - Determination of amphotericin B, liposomal amphotericin B, and amphotericin B
      colloidal dispersion in plasma by high-performance liquid chromatography.
AB  - Amphotericin B is a potent polyene antifungal drug for intravenous treatment of
      severe infections. It is used as amphotericin B-deoxycholate and in order to
      reduce amphotericin B toxicity as lipid-formulated complex (liposomal or
      colloidal dispersion). A sensitive and specific analytical method is presented
      for the separation of lipid-complexed and plasma protein-bound amphotericin B in
      human heparinized plasma. This separation, which is required for pharmacokinetic
      studies, is achieved by solid-phase extraction (SPE) via Bond Elut C18. The
      protein-bound amphotericin B has a higher affinity to the SPE material and is
      therefore retained, whereas the lipid-complexed amphotericin B is eluted in the
      first step. The recovery of the SPE was >75% for high concentrations and >95% for
      low concentrations. Quantification was performed by reversed-phase HPLC using a
      LiChrosorb-RP-8 column, UV detection (lambda=405 nm) and a mixture of
      acetonitrile-methanol-0.010 M NaH2PO4 buffer (41:10:49, v/v) as mobile phase. The
      retention time for amphotericin B under the given conditions was 6.7 min. The
      calibration curves were found to be linear (r > or = 0.999) in two different
      ranges (5.0-0.50 microg/ml and 0.50-0.005 microg/ml). Intra- and inter-day
      precision and accuracy fulfilled the international requirements. No interference
      from other drugs (typical broad medication for intensive-care patients) or common
      plasma components was detected in >400 samples analyzed.

PMID- 11530991
TI  - The recovery of self tolerance in SLE.

PMID- 11530992
TI  - CD5+ B cells in nonorgan-specific autoimmune diseases: a fresh look.

PMID- 11530993
TI  - Pre-treatment affinity for LJP 394 influences pharmacodynamic response in lupus
      patients.
AB  - Five prospective clinical studies in lupus patients have shown that LJP 394 can
      reduce circulating anti-dsDNA antibody levels without causing generalized
      immunosuppression. The compound is currently being evaluated in a phase III
      clinical trial for the prevention of renal flares in patients with high-affinity
      antibodies to LJP 394 and a history of lupus nephritis. The current study
      analyzed the affinity of patient IgG for LJP 394 prior to and following 4 months
      of treatment with LJP 394 to determine if pretreatment affinity influenced
      pharmacodynamic response. Patient serum samples from a multicenter, double-blind,
      placebo-controlled trial were evaluated prior to and following 4 months of
      weekly, biweekly or monthly treatment with placebo (n = 9) or weekly treatment
      with 10 mg LJP 394 (n = 6) or 50 mg LJP 394 (n = 4). After treatment there was a
      dose-dependent reduction in affinity in the 10 mg/week and 50 mg/week groups (P <
      0.05 and P < 0.01, respectively), whereas the placebo group was unchanged. This
      study demonstrates that weekly treatment with LJP 394 produces a dose-dependent
      reduction in titer-weighted average affinity. These results suggest it may be
      possible to use an affinity assay to define prospectively patients that are most
      likely to exhibit the desired pharmacodynamic response to LJP 394.

PMID- 11530994
TI  - Association of beta2-glycoprotein I IgG and IgM antibodies with thrombosis and
      thrombocytopenia.
AB  - Antiphospholipid antibodies (APA) have been known for decades. Their relation to
      clinical manifestations, primarily thromboses and thrombocytopenia, was
      recognised in the 1980s. In this clinical study two cohorts of patients, a
      population-based (84 patients with systemic lupus erythematosus (SLE)) and a
      hospital-based (87 patients with SLE and 53 with other connective tissue
      diseases) were investigated for APA and associated clinical manifestations.
      Anticardiolipin antibodies (ACA) of IgG and IgM classes were found in 13 and 38%
      of the population-based patients and in 29 and 58% of the hospital-based
      patients, respectively. The corresponding figures for antibodies against beta2
      glycoprotein I (anti-beta2GPI) were 15 and 10% in the population-based patients
      and 14 and 8% in the hospital-based cohort. Anti-beta2GPI antibodies were always
      found in association with the corresponding immunoglobulin class of ACA. In both
      cohorts anti-beta2GPI of the IgG class were associated with arterial/venous
      occlusion, a result concordant with other studies. A novel finding in both
      cohorts, however, was an association between thrombocytopenia and IgM anti
      beta2GPI.

PMID- 11530995
TI  - Autoreactive murine Th1 and Th2 cells kill syngeneic macrophages and induce
      autoantibodies.
AB  - D10 cells, a cloned Th2 line, become autoreactive following treatment with DNA
      methylation inhibitors like 5-azacytidine (5-azaC), and induce anti-DNA
      antibodies if injected into unirradiated syngenic mice. The mechanism by which
      the autoreactive cells break tolerance is unknown. To further define effector
      functions required, we asked if 5-azaC-treated Th1 cells could also induce
      autoimmunity. AE7 cells, a cloned Th1 line, were treated with 5-azaC and shown to
      become autoreactive and induce anti-DNA antibodies in vivo. Comparison of
      effector mechanisms demonstrated that the two cell lines secreted a distinct
      repertoire of cytokines, and that only killing of syngeneic Mo was common to both
      AE7 and D10 cells. This suggests that Mo killing may be an early step in the
      induction of anti-DNA antibodies, providing antigenic nucleosomes and decreasing
      clearance of apoptotic material. Secretion of cytokines promoting B cell
      differentiation may play a role, but no one cytokine is required.

PMID- 11530996
TI  - Can B cell epitopes of 60 kDa Ro distinguish systemic lupus erythematosus from
      Sjogren's syndrome?
AB  - Antibodies binding components of the Ro/La (or SSA/SSB) ribonucleoprotein
      particle are found in the sera of patients with systemic lupus erythematosus
      (SLE) and Sjogren's syndrome (SS) as well as mothers who give birth to babies
      with neonatal lupus. Anti-La occurs in a subset of sera that contain anti-Ro, and
      anti-La is found more commonly in sera of patients with SS than in sera from SLE
      patients. The fine specificity of autoantibodies binding 60 kDa has been studied
      extensively. Recent data have suggested that there are disease-specific epitopes
      which identify patients with either SLE or SS. Alternatively, other data suggest
      that the B cell epitopes of 60kDa Ro vary according to the presence of anti-La.
      The present study was undertaken to determine whether binding of putative disease
      specific 60 kDa Ro epitopes is associated with the diagnosis of SLE vs SS, or
      instead associated with the presence of anti-La. Anti-60 kDa Ro positive sera
      from 24 SLE patients and 44 SS patients were studied for antibodies binding two
      epitopes of 60 kDa Ro. We find the epitope defined by residues 171-190 is
      associated with anti-60 kDa Ro without anti-La, regardless of diagnosis.
      Meanwhile, binding of the epitope defined by residues 215-232 is not commonly
      found in anti-60 kDa Ro sera, especially in those sera with both anti-60 kDa Ro
      and anti-La. Thus, the fine specificity of antibody binding to 60 kDa Ro varies
      according to the presence of anti-La, not to the diagnosis of either SLE or SS.

PMID- 11530997
TI  - Enhanced serum prolactin (PRL) in patients with systemic lupus erythematosus: PRL
      levels are related to the disease activity.
AB  - Recent accumulated evidence suggests that prolactin (PRL) is an important
      immunomodulator and plays a part in the pathogenesis of systemic lupus
      erythematosus (SLE). The current study assessed the frequency of
      hyperprolactinaemia in patients with SLE and its association with defined
      clinical manifestations or serological abnormalities. PRL levels were analysed in
      60 patients with SLE including a follow-up of 20 patients, 18 patients with
      rheumatic autoimmune diseases other than SLE (AID) and in 47 normal healthy
      subjects (NHS) using ELISA. Clinical manifestations and disease activity (ECLAM)
      were recorded. Autoantibodies (anti-dsDNA, anti-CL) were determined by standard
      techniques. In all, 28.3% of the patients with SLE had raised serum PRL. Their
      PRL levels (17.4+/-15.1 ng/ml, P<0.0001) and those of patients with AID (13.1+/
      10.3 ng/ml, P<0.001) were significantly higher compared to NHS (6.3+/-3.2 ng/ml).
      Anti-dsDNA (r(s) = 0.3, P = 0.04) and anti-CL antibody titres (IgG; r(s) = 0.3, P
      = 0.03) correlated with PRL level. Furthermore, elevated erytthrocyte
      sedimentation rate (ESR), anaemia, decrease in C3, fatigue, fever and renal
      involvement were associated with hyperprolactinaemia. These results were
      confirmed by follow-up examinations. Moderate hyperprolactinaemia is present in a
      subset of patients with SLE and serum PRL correlates with clinical and
      serological disease activity.

PMID- 11530998
TI  - Suppression of renal disease and mortality in the female NZB x NZW F1 mouse model
      of systemic lupus erythematosus (SLE) by chenodeoxycholic acid.
AB  - The objective of this study was to examine the effects of ursodeoxycholic (UDCA)
      and chenodeoxycholic acid (CDCA) on autoimmune disease in the NZB x NZW F1 (B/W)
      mouse model of systemic lupus erythematosus (SLE). The development of murine
      lupus was assessed in female B/W mice given UDCA or CDCA. At 6 week intervals
      mice were examined for weight change, albuminuria, anti-DNA antibody and total
      IgG levels. Morbidity and mortality were assessed daily. UDCA- and CDCA-treated
      mice were examined at 24 weeks of age for serum cytokines, lymphocyte phenotype,
      and in vitro cytokine production after immunization with DNP-KLH. Liver and
      kidneys were examined histopathologically. The administration of UDCA and CDCA
      was tolerated without side effects. Weight gain in UDCA- or CDCA-treated and
      control mice was identical through 24 weeks of age. CDCA, but not UDCA,
      suppressed the development of renal disease. CDCA-treated B/W mice also had
      improved survival compared to UDCA-treated or control B/W mice. There were no
      significant effects of CDCA on anti-DNA antibodies, serum total IgG, or other
      immunologic parameters. CDCA-treated mice had lower serum IFN-gamma
      concentrations compared to control and UDCA-treated mice. The bile acid, CDCA,
      significantly inhibited the development of renal disease and modestly prolonged
      lifespan in the female B/W mouse model of SLE. Suppression of glomerulonephritis
      was associated with lower serum IFNgamma concentrations. Further investigation is
      needed to verify potential mechanisms of action, but these findings suggest that
      bile acids may alter the development or progression of autoimmunity.

PMID- 11530999
TI  - Antiphospholipid antibody levels in intravenous immunoglobulin (IVIg)
      preparations.
AB  - The antiphospholipid syndrome (APS) is characterized by various clinical
      manifestations and by elevated levels of antiphospholipid antibodies. Passive
      induction of APS by infusion of these antibodies has been demonstrated in animal
      models. Intravenous immunoglobulin (IVIg) is one of the therapeutic options in
      APS. In this study, five commercially used preparations of IVIg were tested for
      the presence of elevated levels of cardiolipin, beta-glycoprotein-I,
      phosphatidylserine, antinuclear, and double-stranded DNA autoantibodies, as well
      as for lupus anticoagulant activity. The absence of abnormal elevated levels of
      any of these autoantibodies in five different IVIg preparations provides
      additional evidence for the safety of IVIg use in APS.

PMID- 11531000
TI  - Chorioretinopathy and discoid plaque-like lesions of the eyelids as useful
      indicators of systemic lupus erythematosus (SLE) progression.
AB  - Choroidal involvement in systemic lupus erythematosus (SLE) occurs infrequently.
      We report a 45-y-old woman with bilateral chorioretinopathy associated with SLE.
      Diagnosis was performed using indirect ophthalmoscopy, retinal fluorescein
      angiography (FA) and green indocianin angiography (ICG). In this patient
      chorioretinopathy and discoid-like plaque of the lids represented the only signs
      of SLE progression after 15 y of apparent remission of systemic disease.

PMID- 11531001
TI  - Foetal loss, liver necrosis and acute lupus erythematosus in a patient with
      antiphospholipid antibody syndrome.
AB  - The antiphospholipid antibody syndrome (APS) is characterized by arterial or
      venous thromboses and recurrent foetal loss. It occurs as primary disease, but
      also in the context of systemic lupus erythematosus (SLE). Whereas primary APS
      induces a thrombotic microangiopathy without significant inflammatory reaction,
      secondary APS in SLE is usually associated with vasculitis. Here we report a
      patient with APS who presented with acute diarrhoea and then developed a HELLP
      like syndrome characterized by a spontaneous abortion, multifocal hepatic
      necroses and thrombocytopenia. Thereafter an acute flare of SLE with arthralgias,
      pleuritis, skin rash and glomerulitis occurred. Clinical amelioration was only
      achieved by combining curettage, anticoagulation and immunosuppression, a
      treatment taking into account the pathogenesis of HELLP-like disease, APS and
      SLE. To our knowledge this is the first reported case of APS associated with
      combined acute manifestations of these three syndromes triggered by a presumable
      intestinal infection.

PMID- 11531002
TI  - The Sixth International Lupus Conference, Barcelona 24-28 March 2001.

PMID- 11531003
TI  - Characterization of moclobemide N-oxidation in human liver microsomes.
AB  - 1. Moclobemide underdergoes morpholine ring N-oxidation to form a major
      metabolite in plasma Rol2-5637. 2. The kinetics of moclobemide N-oxidation in
      human liver microsomes (HLM) (n = 6) have been investigated and the mixed
      function oxidase enzymes catalysing this reaction have been identified using
      inhibition, enzyme correlation, altered pH and heat pretreatment experiments. 3.
      N-oxidation followed single enzyme Michealis-Menten kinetics (0.02-4.0 mm). Km
      app and Vmax ranged from 0.48 to 1.35 mM (mean +/- SD) 0.77 +/- 0.34 mM) and 0.22
      to 2.15 nmol mg(-1) min(-1) (1.39 +/- 0.80 nmol mg(-1) respectively. 4. The N
      oxidation of moclobemide strongly correlated with benzydamine N-oxidation a probe
      reaction for flavin-containing monoxygenase (FMO) activity (0.1 mM moclobemide,
      rs = 0.81, p < 0.005; 4 mM moclobemide, rs = 0.94, p = 0.0001). Correlations were
      observed between moclobemide N-oxidation and specific cytochromre P450 (CYP)
      activities at both moclobemide concentrations (0.1 mM moclobemide, CYP2C19 0.66,
      p < 0.05; 4 mM moclobemide, CYP2E1 rs = 0.56, p < 0.05). 5. The general P450
      inhibitor, N-benzylimidazole, did not affect the rate of Rol2-5637 formation (0%
      inhibition versus control) (at 1.3 mM moclobemide. Furthermore, the rate of Ro12
      5637 formation in HLM was unaffected by inhibitors Or substrates of specific
      P450s (< 10% inhibition versus control). 6. Heat pretreatment of HLM in the
      absence of NADPH (inactivating FMOs) resulted in 97% inhibition of Ro12-5637
      formation. N-oxidation activity was greatest when incubated at pH 8.5. These
      results ilre consistent with the reaction being FMO medialtetd . 7. In
      conclusion, moclobemide N-oxidation activity has been observed in HLM in vitro
      and the reaction is predominantly catalysed by FMOs with a potentially small
      contribution from cytochrome P450 isoforms.

PMID- 11531004
TI  - Suppression of CYP3A2 mRNA expression in the warfarin-resistant roof rat, Rattus
      rattus: possible involvement of cytochrome P450 in the warfarin resistance
      mechanism.
AB  - 1. The continual use of warfarin as a rodenticide has caused the development of
      populations of warfarin-resistant roof rat. To study the biochemical mechanism of
      warfarin resistance, the mRNA expression levels of the major P450 forms in the
      warfarin-resistant and -susceptible roof rat liver following exposure to warfarin
      were quantified by competitive RT-PCR. 2. The constitutive levels of CYP2C11 and
      CYP3A2 mRNAs in the warfarin-resistant and -susceptible roof rat were extremely
      low compared with those in the STD rat. In response to warfarin administration,
      the CYP3A2 mRNA level in the warfarin-susceptible rat increased to about 3-fold
      of that before the treatment, whereas in the warfarin-resistant roof rat, CYP3A2
      mRNA remained at a low level. 3. The present results suggest the possibility that
      reduced synthesis of CYP3A2 mRNA is involved in the warfarin-resistant mechanism
      in the roof rat.

PMID- 11531005
TI  - Development of diltiazem deacetylase and demethylase activities during ontogeny
      in rabbit.
AB  - 1. Diltiazem (DTZ) undergoes extensive metabolism in hepatic and extrahepatic
      tissues. Deacetyldiltiazem (M1) and N-desmethyldiltiazem (MA) are two of the main
      basic metabolites of DTZ that retain pharmacological activity. The development of
      DTZ deacetylase and demethylase activities through ontogeny has not been
      addressed. In order to address this issue, in vitro studies have been carried out
      using the blood and several tissues of rabbit as enzyme sources. In addition, in
      vivo studies using a pharmacokinetic approach were carried out to support the in
      vitro findings. 2. DTZ was incubated with homogenates of selected tissues and in
      whole blood and DTZ, and its metabolites were assayed by HPLC. In addition, a
      pharmacokinetic study after intraperitoneal administration of DTZ in the 1-, 8-,
      16-, 30-day-old and adult rabbit were also carried out. 3. DTZ deactylase
      activity was detected whatever the age and tissue examined (including blood).
      Except in gut homogenates, this activity was shown to be higher at earlier
      postnatal ages. DTZ demethylase activity was only detected in the liver and gut
      homogenates and in whole blood. This activity increases from the 1- to 30-day-old
      rabbit (except for blood), after which it decreases slightly to reach the adult
      level. 4. In vivo experiments showed a close pharmacokinetic profile throughout
      ontogeny (except for the 30-day-old rabbit) after DTZ intraperitoneal
      administration. 5. Extrahepatic metabolism may play a more significant role in
      the overall metabolism and pharmacokinetics of DTZ at earlier stages of
      development. 6. Finally, in vivo studies Suggest that age does not seem to modify
      DTZ disposition and, for this reason, dosage may not have to be taken into
      account as a function of age.

PMID- 11531006
TI  - Metabolism of the analgesic drug, tramadol hydrochloride, in rat and dog.
AB  - 1. Metabolism of the analgesic agent, tramadol hydrochloride, was investigated
      after a single oral administration of 14C-tramadol to four rats (50)mgkg(-1) and
      two dogs (20)mg kg(-1). 2. Recovery of total radioactivity in rat and dog urine
      samples over 24 h was 73 and 65% of the radioactive dose, respectively. 3.
      Unchanged tramadol and a total of 24 metabolites, consisting of 16 Phase I
      metabolites and eight conjugates (seven glucuromides, one sulphate), were
      isolated and tentatively identified, which accounted for > 52% of the dose in
      urine of both species. 4. Of the metabolites, five (M1-5) were previously
      identified. 5. The metabolites were formed via the following six metabolic
      pathways: O-demethylation, N-demethylation, cyclohexyl oxidation, oxidative N
      dealkylation, dehydration and conjugation. 6. Pathways 1-3 appear to be major
      steps, forming seven O-desmethyl/N-desmethyl and hydroxy-cyclohexyl metabolites
      in major quantities. 7. Pathways 1-3 in conjunction with pathway 6 produced four
      glucuronides along with four minor conjugates. 8. In addition, the in vitro
      metabolism of tramadol was conducted using rat hepatic S9 fraction in the
      presence of an NADPH-generating system. Unchanged tramadol (30% of the sample)
      plus nine metabolites, M1-7, tramadol-N-oxide (M31) and OH-cyclohexyl-M1 (M32),
      were profiled and tentatively identified based on MS and MS/MS data.

PMID- 11531007
TI  - Metabolism of [14C]1,2,7,8-tetrachlorodibenzo-p-dioxin in a ruminating Holstein
      calf.
AB  - 1. [UL-7,8-ring 14C]-1,2,7,8-tetrachlorodibenzo-p-dioxin (1278-TCDD) was
      administered orally to a ruminating Holstein bull calf (43.6 kg; 1.2 mg kg(-1)
      body weight). Urine and faeces were collected daily for 96 h, while blood was
      sampled at multiple time points. Tissues were removed for combustion analysis. 2.
      Each tissue contained < 0.65 of the dose at 96h. Tissues with highest levels of
      1278-TCDD, as a percentage of administered dose, were the large and small
      intestine, rumen, liver and carcass. 3. Urinary excretion accounted for 10.6% of
      the dose, and faecal excretion accounted for 81.6% of the administered dose. The
      major urinary and faecal metabolites were isolated and characterized by mass
      spectrometry and 1H-NMR. 4. Plasma levels of 14C peaked at 24h, and decreased to
      near background at 96 h. Detectable plasmal levels of 1278-TCDD were observed by
      2 h. 5. A hydroxylated metabolite of 1278-TCDD was detected in calf plasma, which
      has the potential to interfere with thyroid hormone homeostasis.

PMID- 11531008
TI  - Awareness of genetic testing for breast cancer risk among women with a family
      history of breast cancer: effect of women's information sources on their
      awareness.
AB  - The purpose of this study was to relate women's awareness of breast cancer risk
      genetic testing to the sources of information used by women for obtaining
      information about breast health. A sample of 354 women with a family history of
      breast or ovarian cancer was interviewed. Study variables included women's
      information sources for breast health, personal risk perceptions, family history
      of breast cancer, personal experience (i.e., having had a biopsy), awareness of
      genetic testing, and demographic variables. Regression analyses were conducted to
      assess the relationships among the variables. Only approximately one-third of the
      study participants were moderately aware of genetic testing for breast cancer
      risk. The Internet Web was the only information source significantly related to
      awareness of genetic testing. Having had a biopsy, being more highly educated,
      and being married also were significant predictors of awareness of genetic
      testing. Study participants were not uniformly aware of genetic testing. If the
      diffusion of Web technology continues, the Web may be a promising source for
      increasing awareness on genetic testing for breast cancer risk.

PMID- 11531009
TI  - Immunoperoxidase detection of polycyclic aromatic hydrocarbon-DNA adducts in
      breast tissue sections.
AB  - Although the etiology of the majority of human breast cancers is unknown,
      environmental carcinogens are suspected to play a role. In this study, we
      investigated polycyclic aromatic hydrocarbon-DNA adducts in 78 breast cancer
      patients and benign breast disease patients with lifetime environmental exposure
      to polycyclic aromatic hydrocarbon (PAH) compounds. Adducts were detected in
      paraffin sections by immunoperoxidase method using polyclonal antiserum and were
      quantitated by the image-analyzing system. A significantly higher level of
      adducts was found in benign breast disease as compared to cancer patients (P <
      .001; Mann-Whitney U test). Neither smoking nor genetic polymorphisms in
      glutathione S-transferase and cytochrome P450 influenced the level of adducts.
      This exploratory study demonstrates the usefulness of the immunoperoxidase method
      to detect PAH-DNA adducts in stored breast tissue and suggests further research
      on a larger population, including patients from both high- and low-pollution
      environments.

PMID- 11531010
TI  - Integration of peripheral blood biomarkers with computed tomography to
      differentiate benign from malignant pulmonary opacities.
AB  - Our purpose was to determine whether peripheral blood biomarkers MUC1 and CK19
      could be used to complement imaging studies in differentiating benign from
      malignant indeterminate pulmonary nodules or masses detected on computed
      tomography CT. One hundred and eighteen patients had a thoracic CT and blood
      drawn for tumor marker reverse transcriptase-polymerase chain reaction analysis.
      Thirty-five of the 118 patients had an indeterminate pulmonary nodular opacity on
      CT, and the findings then were correlated with the reverse transcriptase
      polymerase chain reaction results. The sensitivity and specificity for the
      markers in determining malignancy was calculated. Thirteen of the 35 opacities on
      CT proved to be benign, and 22 proved to be lung cancer. Among the patients with
      indeterminate pulmonary abnormalities, polymorphic epithelial mucin protein 1 had
      a sensitivity and specificity for lung cancer of 100% and 46%, respectively.
      Cytokeratin 19 had a sensitivity and specificity for lung cancer of 95% and 8%,
      respectively. These preliminary data showed that serum biomarkers polymorphic
      epithelial mucin protein 1 and cytokeratin 19 were not specific for lung cancer,
      although patients with an indeterminate pulmonary abnormality and negative
      markers were unlikely to have lung cancer. Integration of imaging studies with
      the appropriate biomarkers may prove useful in evaluating indeterminate pulmonary
      nodules or masses.

PMID- 11531011
TI  - Carcinoembryonic antigen and CA19-9: implications of quantitative marker
      measurement in tissues for prognosis of colorectal cancer.
AB  - Measurement of tumor markers in serum of colorectal cancer patients after surgery
      is a sensitive method in early diagnosis of systemic spread of tumor cells.
      Moreover, prognostic association of carcinoembryonic antigen (CEA) content in
      serum at the time of surgery is well known. However, fairly unclear is whether
      quantitative content of CEA and CA19-9 in cancer tissue and adjacent normal
      mucosa of colorectal cancer patients is correlated to prognosis. Concentrations
      of CEA and CA]9-9 were analyzed simultaneously in serum, cancer tissue, and
      normal colonic mucosa of 41 colorectal cancer patients operated for cure. Follow
      up data were available for up to 82 months (median, 47 months) after surgery.
      During the follow-up period, 20 patients had a tumor recurrence, and all these
      patients died of metastatic disease. Using the median concentration of CEA and
      CA19-9 in tissues as a cut-off, no difference in overall and disease-free
      survival was observed between patients with elevated or normal CEA or CA19-9
      concentrations in tumor tissue. However, in adjacent histologically normal
      mucosa, elevated CEA content was associated with significantly shorter overall
      survival (P = .0385) and disease-free survival (P = .0141) but not CA19-9
      content. Despite the unknown biological function of tumor markers in malignant
      disease, measurement of tumor-associated antigens in colorectal tissues can
      become an interesting prognostic marker.

PMID- 11531012
TI  - Chronic dosing of oltipraz in people at increased risk for colorectal cancer.
AB  - The dithiolethione oltipraz is being developed as a chemopreventive agent for
      many malignancies, including colorectal cancer, on the basis of its in vivo
      protective activity against chemically induced tumors in a variety of animal
      models. This protection has been associated with an enhanced capacity to detoxify
      reactive carcinogens and, more recently, with increased DNA repair. In a previous
      single-dose study, elevated detoxification gene expression was observed in the
      days after oltipraz dosing. Now, in this clinical study, we evaluated the effects
      of oltipraz when given over a 3-month period. Fourteen individuals with increased
      risk for colorectal cancer were randomly assigned to one of two oral doses (125
      or 250 mg/m2) of oltipraz twice weekly for 12 weeks. Two of seven subjects at the
      250 mg/m2 dosage required dose reductions, owing to significant fatigue. The 125
      mg/m2 dose level was well tolerated by all patients. Blood or colon tissue (or
      both) for evaluation of glutathione, glutathione S-transferase, DT-diaphorase
      activity, and DT-diaphorase mRNA expression were obtained prior to treatment and
      at weeks 6, 12, and 16. No significant modulation of phase II detoxification
      enzymes was seen at either dose studied during this period. Phase II trials
      evaluating a tolerable regimen of oltipraz (as demonstrated in this study) and
      other possible mechanisms that may be responsible for the protective activity of
      oltipraz should be pursued.

PMID- 11531013
TI  - Inhibitory effects of thymoquinone against 20-methylcholanthrene-induced
      fibrosarcoma tumorigenesis.
AB  - The potential antitumor effect of thymoquinone (TQ), the main constituent of the
      volatile oil of Nigella sativa seed, on fibrosarcoma induced by 20
      methylcholanthrene (MC) in male Swiss albino mice was investigated in vivo and in
      vitro. Administration of TQ (0.01% in drinking water) I week before and after MC
      treatment significantly inhibited the tumor incidence and tumor burden by 43% and
      34%, respectively, compared with the results in the group receiving MC alone.
      Moreover, TQ delayed the onset of MC-induced fibrosarcoma tumors that appeared at
      12 weeks and produced less MC-induced mortality. Lipid peroxide accumulation,
      decreased glutathione (GSH) content, and decreased activities of glutathione S
      transferase (GST) and quinone reductase (QR) were observed in the liver of MC
      induced tumor-bearing mice. TQ alone showed a significant induction in the enzyme
      activities of hepatic GST and QR. Mice treated with TQ along with MC showed
      reduction in hepatic lipid peroxides and increased GSH content and increased
      enzyme activities of GST and QR as compared to results of the control group. The
      in vitro studies showed that TQ inhibited the survival of fibrosarcoma cells with
      IC50 of 15 microM. Conversely, TQ inhibited the incorporation of [3H] thymidine
      in fibrosarcoma cells with IC50 of microM. Our data indicate the potential of TQ
      as a powerful chemopreventive agent against MC-induced fibrosarcoma tumors. The
      possible modes of action of TQ may be through its antioxidant activity and
      interference with the DNA synthesis coupled with enhancement of detoxification
      processes.

PMID- 11531014
TI  - A comparative study on cytogenetic and antineoplastic effects induced by two
      modified steroidal alkylating agents.
AB  - We investigated the effects of two newly synthesized steroidal derivatives of
      nitrogen mustard on sister chromatid exchange rates and on human lymphocyte
      proliferation kinetics. The compound 33-hydroxy-5alpha,22alpha-spirostan- 12-one
      p-(N,N-bis(2-chloroethyl)amino)phenylacetate(1) was, on a molar basis, less
      effective in inducing sister chromatid exchange and suppressing cell
      proliferation rate indices than compound 3beta-hydroxy-12alpha-aza-C-homo
      5alpha,22alpha-spirostan-12-one-p-(N,N-bis(2-chloroethyl)amino)phenylacetate(2).
      A correlation was observed between the magnitude of the sister chromatid exchange
      response and the depression of cell proliferation index. We also studied the
      effects of the aforementioned compounds on Lewis lung carcinoma. The order of the
      percent inhibition of tumor growth achieved by the compounds coincides with the
      order of the cytogenetic effects they induce.

PMID- 11531015
TI  - Interactions between the PI3K and Raf signaling pathways can result in the
      transformation of hematopoietic cells.
AB  - The PI3K/Akt and Raf/MEK/ERK signal transduction cascades are pivotal in
      transmitting signals from membrane receptors to downstream targets that regulate
      apoptosis, gene expression, and cell growth. The abilities of activated PI3K,
      Akt, Raf, and MEK proteins to abrogate the cytokine dependence of three different
      hematopoietic cell lines were determined. Activated PI3K or Akt expression by
      themselves did not efficiently annul cytokine dependence. Raf and MEK could
      abrogate the cytokine dependence of murine FDC-PI and human TF-1 cells; however,
      the frequency of transformation was dependent on the particular oncogene
      examined, as more factor-independent cells were isolated after infection with
      activated retroviruses encoding A-Raf or Raf-1 than were with MEK1 or B-Raf.
      Cytokine-independent deltaRaf-1-infected cells formed tumors on injection into
      immunocompromised mice, whereas cytokine-dependent cell lines did not,
      demonstrating the oncogenic effects of activation of the Raf/MEK/ERK pathway.
      Overexpression of the antiapoptotic Bcl-2 protein synergized with activation of
      the Raf/MEK/ERK cascade and increased the efficiency of transformation of FDC-PI
      and TF-1 cells. In contrast to the results observed with FDC-P1 and TF-I cells,
      the activated Raf genes did not relieve the cytokine dependence of murine FL5.12
      cells. The abilities of the Raf and PI3K pathways to interact and annul the
      cytokine dependence of FL5.12 cells were determined. The combination of Raf and
      either PI3K or Akt expression relieved cytokine dependence of some FL5.12 cells,
      and the efficiency of transformation could be enhanced further by Bcl-2 or Bcl-XL
      overexpression. Thus, the antiapoptotic PI3K/Akt and Bcl-2/Bcl-XL proteins can
      interact with the growth-promoting Raf/MEK/ERK pathway and annul the cytokine
      dependence of certain hematopoietic cells.

PMID- 11531016
TI  - Expression  pattern of hybrid phenotype in adult acute lymphoblastic leukemia.
AB  - We examined the expression of hybrid phenotype in 236 adults with acute
      lymphoblastic leukemia (ALL; 188 B-lineage ALL and 48 T-lineage ALL). In B
      lineage ALL, myeloid antigen (mAg) CD15 was concentrated in CD10-CD20- cases
      (49%); CD13 (42%); and CD33 (43%) in CD10+CD20- cases. This trend had no
      correlation with the presence of Ph1 or t(4;11) chromosomal abnormality. T-cell
      antigen CD2, CD4, and CD7 was seen in four, four, and two cases, respectively,
      and CD4+ and CD7+ cases commonly expressed CD13 and/or CD33 (CD13/CD33). In T
      lineage ALL, expression of mAg, CD11b (47%), CD13 (38%), CD15 (28%), and CD33
      (51%) was restricted to CD3- cases. B-cell antigen CD19 was found in two cases
      with CD7 solely as T-cell antigen, and these cases possessed CD13/CD33. CD21 was
      detected in three cases with CD3. In whole ALL, CD13/CD33 was associated closely
      with the presence of stem-cell antigen CD34, and in T-lineage ALL, CD13/CD33 had
      a significant correlation with additional stem-cell features, such as HLA-DR,
      multidrug resistance 1 (MDR1) and c-kit gene expression. Our results suggest that
      immature ALL cells frequently express B+M+, T+M+, and occasionally B+T+M+
      phenotype; that B+T+M- phenotype is extremely rare; and that mAg expression in B
      lineage ALL is complicated as compared to T-lineage ALL.

PMID- 11531017
TI  - Role of cerebral inflammation after traumatic brain injury: a revisited concept.
AB  - Neuroinflammation occuring after traumatic brain injury (TBI) is a complex
      phenomenon comprising distinct cellular and molecular events involving the
      injured as well as the healthy cerebral tissue. Although immunoactivation only
      represents a one of the many cascades initiated in the pathophysiology of TBI,
      the exact function of each mediator, activated cell types or pathophysiological
      mechanism, needs to be further elucidated. It is widely accepted that
      inflammatory events display dual and opposing roles promoting, on the one hand,
      the repair of the injured tissue and, on the other hand, causing additional brain
      damage mediated by the numerous neurotoxic substances released. Most of the data
      supporting these hypotheses derive from experimental work based on both animal
      models and cultured neuronal cells. More recently, evidence has been provided
      that a complete elimination of selected inflammatory mediators is rather
      detrimental as shown by the attenuation of neurological recovery. However, there
      are conflicting results reported on this issue which strongly depend on the
      experimental setting used. The history of immunoactivation in neurotrauma is the
      subject of this review article, giving particular emphasis to the comparison of
      clinical versus experimental studies performed over the last 10 years. These
      results also are evaluated with respect to other neuropathologies, which are
      years ahead as compared to the research in TBI. The possible reciprocal influence
      of peripheral and intrathecal activation of the immune system will also be
      discussed. To conclude, the future directions of research in the field of
      neurotrauma is considered.

PMID- 11531018
TI  - Peptidoglycan primes for LPS-induced release of proinflammatory cytokines in
      whole human blood.
AB  - The pathophysiological mechanisms involved in mixed bacterial infections caused
      by gram-positive and gram-negative bacteria are largely unknown. The present
      study examines the potential interaction between lipopolysaccharide (LPS) and
      peptidoglycan (PepG) in the induction of the sepsis-associated cytokines tumor
      necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and IL-10 in whole human
      blood. Plasma values of these cytokines were measured by enzyme immunoassays and
      a TNF bioassay. Co-administration of PepG (10 microg/mL) or muramyl dipeptide
      (MDP, 1 microg/mL) with LPS (10 ng/mL) caused significantly elevated values of
      TNF-alpha and IL-6 in the blood that could not be obtained by the sum of the
      values obtained by each stimulant alone, or by 3-fold higher doses of either
      bacterial component alone. This phenomenon was observed 1 h after stimulation,
      throughout the experimental period (24 h), and with different doses of LPS and
      PepG. In contrast, the release of IL-10 was not influenced by the co
      administration of PepG or MDP with LPS. The TNF-alpha release induced by co
      administration of LPS and PepG was abrogated after pretreatment with a monoclonal
      antibody against CD14 (18D11). Addition of PepG or MDP to whole blood caused a 2
      fold increase in the surface expression of CD14 on monocytes, as measured by flow
      cytometry. In contrast, LPS caused decreased expression of this receptor. Our
      data suggest that PepG and MDP primes human whole blood leukocytes for LPS
      induced release of proinflammatory cytokines. We speculate that synergy between
      PepG and LPS may contribute to the pathogenesis in sepsis caused by mixed
      bacterial infections.

PMID- 11531019
TI  - PGE2 suppresses intestinal T cell function in thermal injury: a cause of enhanced
      bacterial translocation.
AB  - Increased gut bacterial translocation in burn and trauma patients has been
      demonstrated in a number of previous studies, however, the mechanism for such an
      increased gut bacterial translocation in injured patients remains poorly
      understood. Utilizing a rat model of burn injury, in the present study we
      examined the role of intestinal immune defense by analyzing the T cell functions.
      We investigated if intestinal T cells dysfunction contributes to bacterial
      translocation after burn injury. Also our study determined if burn-mediated
      alterations in intestinal T cell functions are related to enhanced release of
      PGE2. Finally, we examined whether or not burn-related alterations in intestinal
      T cell function are due to inappropriate activation of signaling molecule P59fyn,
      which is required for T cell activation and proliferation. The results presented
      here showed an increase in gut bacterial accumulation in mesenteric lymph nodes
      after thermal injury. This was accompanied by a decrease in the intestinal T cell
      proliferative responses. Furthermore, the treatments of burn-injured animals with
      PGE2 synthesis blocker (indomethacin or NS398) prevented both the decrease in
      intestinal T cell proliferation and enhanced bacterial translocation. Finally,
      our data suggested that the inhibition of intestinal T cell proliferation could
      result via PGE2-mediated down-regulation of the T cell activation-signaling
      molecule P59fyn. These findings support a role of T cell-mediated immune defense
      against bacterial translocation in burn injury.

PMID- 11531020
TI  - Hypoxia combined with Escherichia coli produces irreversible gut mucosal injury
      characterized by increased intestinal cytokine production and DNA degradation.
AB  - The objective of the present study was to determine whether hypoxia/reoxygenation
      in the absence or presence of intestinal bacteria would affect the integrity of
      the gut mucosal epithelium (as evidenced by histologic changes) and increase the
      local production of cytokines (interleukin 6 [IL-6] and tumor necrosis factor
      [TNF]). Rat ileal mucosal membranes were harvested and their electrophysiologic
      properties and barrier function were measured ex vivo in the Ussing chamber
      system. Membranes were exposed to normoxia, normoxia + Escherichia coli, hypoxia
      for 40 min followed by normoxia, or hypoxia for 40 min + E. coli followed by
      normoxia for 3 h. IL-6 and TNF levels were measured using cytokine-dependent
      cellular assays. Morphological changes and the degree of DNA fragmentation were
      used as quantitative markers of gut mucosal injury. Mucosal integrity was
      maintained in the normoxia group. The addition of bacteria increased the IL-6
      response and reduced mucosal integrity. During the hypoxic period, a transient
      decline in resistance (R) occurred and cytokine production was reduced. In the
      hypoxic ileal membranes not exposed to E coli, reoxygenation reversed the change
      in R and increased IL-6 production. The combination of hypoxia/reoxygenation plus
      E. coli bacterial challenge resulted in the greatest extent of gut mucosal injury
      and increase in TNF production. The results of this study support the hypothesis
      that the combination of increased intestinal bacterial levels superimposed on an
      ischemia/reperfusion injury increases the magnitude of gut mucosal injury and the
      production and subsequent release of proinflammatory cytokines.

PMID- 11531021
TI  - Inhibition of adenosine deaminase attenuates endotoxin-induced release of
      cytokines in vivo in rats.
AB  - The purpose of this study was to investigate in vivo the effects of modulating
      the adenosine system on endotoxin-induced release of cytokines and changes in
      heart performance and neurohumoral status in early, profound endotoxemia in rats.
      Time/pressure variables of heart performance and blood pressure were recorded
      continuously, and plasma levels of tumor necrosis factor alpha (TNFalpha),
      interleukin 1-beta (IL-1beta), plasma renin activity (PRA), and catecholamines
      were determined before and 90 min after administration of endotoxin (30 mg/kg of
      lipopolysaccharide, i.v.). Erythro-9[2-hydroxyl-3-nonyl] adenine (EHNA; an
      adenosine deaminase inhibitor) had no effects on measured time-pressure variables
      of heart performance under baseline conditions and during endotoxemia, yet
      significantly attenuated endotoxin-induced release of cytokines and PRA.
      Pretreatment with the non-selective adenosine receptor antagonist DPSPX not only
      prevented the effects of EHNA but also increased the basal release of cytokines
      and augmented PRA. At baseline, caffeine (a non-selective adenosine receptor
      antagonist) increased HR, +dP/dtmax, heart rate x ventricular pressure product
      (HR x VPSP) and +dP/dtmax normalized by pressure (+dP/dtmax/VPSP), and these
      changes persisted during endotoxemia. Caffeine attenuated endotoxin-induced
      release of cytokines and augmented endotoxin-induced increases in plasma
      catecholamines and PRA. Pretreatment with propranolol abolished the effects of
      caffeine on heart performance and neurohumoral activation during the early phase
      of endotoxemia. 6N-cyclopentyladenosine (CPA; selective A1 adenosine receptor
      agonist) induced bradicardia and negative inotropic effects, reduced work load
      (i.e., decreased HR, VPSP, +dP/dtmax, +dP/dtmax/VPSP and HR x VPSP) and inhibited
      endotoxin-induced tachycardia and renin release. CGS 21680 (selective A2A
      adenosine receptor agonist) decreased blood pressure under basal condition but
      did not potentiate decreases in blood pressure during endotoxemia. CGS 21680
      completely inhibited endotoxin-induced release of TNFalpha, augmented sympathetic
      activity and PRA, and increased +dP/dtmax and +dP/dtmax/VPSP in the absence and
      presence of endotoxin. The present study provides strong evidence that inhibition
      of adenosine deaminase reduces cytokine release in vivo without producing
      significant hemodynamic and cardiac effects during the early phase of profound
      endotoxemia in rats. The augmented neurohumoral activation induced by caffeine is
      associated with decreased cytokine release induced by endotoxin. Further studies
      are warranted to determine the impact of these effects on cardiac function and
      hemodynamics in the late phase of endotoxemia.

PMID- 11531022
TI  - Effects of selective iNOS inhibition on gut and liver O2-exchange and energy
      metabolism during hyperdynamic porcine endotoxemia.
AB  - We have previously demonstrated that non-selective nitric oxide synthase (NOS)
      inhibition did not reverse the LPS-induced deterioration of hepato-splanchnic
      energy status in porcine endotoxic shock. Therefore, this study investigated the
      effect of selective inducible NOS (iNOS) inhibition using 1400 W on intestinal
      and liver perfusion, O2 kinetics, and energy metabolism during hyperdynamic
      porcine endotoxemia. Intravenous E. Coli LPS was continuously infused over 24 h
      concomitant with fluid resuscitation. After 12 h of endotoxemia, continuous
      intravenous infusion of 1400 W was started until the end of the experiment and
      was titrated to maintain mean blood pressure (MAP) at baseline levels. Twelve,
      18, and 24 h after starting LPS, we measured hepatic arterial and portal venous
      blood flow, ileal mucosal-arterial PCO2 gap, portal as well as hepatic venous
      lactate/pyruvate ratios, and endogenous glucose production rate. Expired NO and
      plasma nitrate levels were assessed as a measure of NO production. 1400 W
      decreased LPS-induced increase in expired NO and allowed for the maintenance of
      MAP without modification of cardiac output. Despite unchanged regional
      macrocirculation, 1400 W prevented the progressive rise of ileal mucosal-arterial
      PCO2 gap, significantly improved the LPS-induced impairment of hepato-splanchnic
      redox state, and blunted the decline in liver lactate clearance. Increased
      glucose production rate was not influenced. Thus, the selective iNOS inhibition
      with 1400 W prevented circulatory failure and largely attenuated otherwise
      progressive LPS-induced deterioration of intestinal and hepatocellular energy
      metabolism.

PMID- 11531023
TI  - Inhibition of nitric oxide synthesis by L-name exacerbates acute lung injury
      induced by hepatic ischemia-reperfusion.
AB  - Hepatic Kupffer cells and pulmonary alveolar macrophages together constitute a
      macrophage-axis involved in the regulation of regional and systemic inflammatory
      responses. Systemic inflammatory response syndrome induced by overproduced pro
      inflammatory mediators is the major cause of adult respiratory distress syndrome.
      In the present study, we examined the anti-inflammatory role of nitric oxide (NO)
      in a rat model of acute lung injury induced by hepatic ischemia-reperfusion
      (HI/R). The left and median lobes of the liver were subjected to 30 min of
      ischemia by clamping the relevant branches of hepatic artery and portal vein,
      followed by a 4-h reperfusion achieved by removal of the vascular clamp. Four
      groups of animals were studied: sham control + saline; sham control + N(omega)
      nitro-L-arginine methyl ester (L-NAME, 10 mg/kg, i.v., 10 min before
      reperfusion); HI/R + saline; HI/R + L-NAME. Results show that (1) administration
      of L-NAME to rats subjected to HI/R decreased plasma NO levels; however, the
      attenuation of NO increased plasma alanine aminotransferase (ALT) activity and
      superoxide generation in the ischemic lobes of liver, compared to HI/R alone. (2)
      Inhibition of NO synthesis with L-NAME in rats subjected to HI/R also enhanced
      systemic inflammatory response as assessed by the increase in the number of
      circulating leukocytes and levels of plasma tumor necrosis factor-alpha
      (TNFalpha) and interleukin 1-beta (IL-1beta). (3) The overwhelming systemic
      inflammatory response induced by administration of L-NAME in rats subjected to
      HI/R also augmented pulmonary vascular permeability and superoxide generation in
      the lung tissue. (4) Pulmonary alveolar macrophages isolated from rats subjected
      to HI/R + L-NAME produced higher levels of TNFalpha and IL-1beta in the
      supernatant of culture medium than that of rats subjected to HI/R alone. (5)
      There were no differences between the groups of sham + saline and sham + L-NAME
      in terms of plasma NO levels and ALT activity, circulating leukocytes, superoxide
      generation in the liver and lung, lavage protein levels, and TNFalpha and IL
      1beta levels in plasma and bronchoalveolar lavage fluid. Our results suggest that
      inhibition of NO synthesis by L-NAME in rats subjected to HI/R not only augments
      ischemic liver injury, but also enhances the systemic inflammatory response and
      exacerbates remote lung injury. The increase in TNFalpha and IL-1beta production
      by alveolar macrophages may, in part, account for L-NAME-induced enhancement of
      acute lung injury.

PMID- 11531024
TI  - Post-hemorrhagic shock mesenteric lymph lipids prime neutrophils for enhanced
      cytotoxicity via phospholipase A2.
AB  - Hemorrhagic shock induced mesenteric hypoperfusion has long been implicated as a
      key event in the pathogenesis of the adult respiratory distress syndrome (ARDS)
      and multiple organ failure (MOF). Previous work links post-hemorrhagic shock
      mesenteric lymph (PHSML) lipids and neutrophil (PMN) priming in the pathogenesis
      of ARDS. We hypothesize that gut phospholipase A2 (PLA2) liberates
      proinflammatory lipids following hemorrhagic shock, which are responsible for
      enhanced PMN cytotoxicity. Mesenteric lymph was collected from rats (n > or = 5)
      before hemorrhagic shock, during hemorrhagic shock (MAP 40 mm Hg x 30 min), and
      after resuscitation (shed blood + 2x lactated Ringers). PMNs were incubated with
      physiologic concentrations (1-5%, v:v) of (a) buffer control, (b) sham (c) pre
      shock lymph, (c) PHSML, (d) PHSML lipid extracts, (e) heat-denatured PSHML, and
      (f) PHSML harvested after i.v. pretreatment with a known PLA2 inhibitor
      (quinacrine, 10 mg/kg). PMNs were activated with fMLP (1 micromol), and the
      maximal rate of superoxide production measured by reduction of cytochrome c. Gut
      morphology was assessed histologically using hematoxalin and eosin (HE) staining.
      PHSML and PHSML lipid extracts (5%, v:v) primed for enhanced superoxide
      production compared to buffer controls (2.5-fold and 3.6-fold), sham (2.5-fold)
      and pre-shock lymph (2.0-fold). Lymph collected after systemic PLA2 inhibition,
      in contrast, abrogated the PMN priming response. Gut mucosal morphology, at end
      resuscitation, was intact on HE staining both with and without PLA2 inhibition.
      Heat denaturing the PHSML (eliminating cytokines and complement), on the other
      hand, did not reduce PMN priming. Physiologic concentrations of PHSML lipids
      prime the PMN respiratory burst. Lymph priming is diminished with systemic PLA2
      inhibition, implicating gut PLA2 as a source of proinflammatory lipids that may
      be central in the pathogenesis of hemorrhagic shock induced ARDS/MOF.

PMID- 11531025
TI  - A rat model of acute lung injury induced by cardiopulmonary bypass.
AB  - Impaired lung function is still a major complication after cardiac surgery with
      cardiopulmonary bypass. The purpose of the present study was to develop an
      experimental model of acute pulmonary injury induced by cardiopulmonary bypass in
      Wistar rats. Cardiopulmonary bypass was performed for 60 min using a non
      pulsatile roller pump and a membrane oxygenator (n = 8 for cardiopulmonary bypass
      group and n = 7 for control rats). We measured tracheal pressure, airflow, and
      lung volume changes and obtained pulmonary resistance and dynamic elastance.
      After the cardiopulmonary bypass, lungs were submitted to a quick-freezing
      protocol and morphometric analysis was performed. There was a time-dependent
      increase in dynamic elastance, but not pulmonary resistance, only in the rats
      submitted to cardiopulmonary bypass (P = 0.005). Lungs from animals submitted to
      cardiopulmonary bypass showed significantly more alveolar hemorrhage (P = 0.025)
      and edema (P = 0.021), as well as perivascular edema (P = 0.003) when compared to
      control rats. In our experimental model, rats submitted to cardiopulmonary bypass
      developed acute pulmonary changes similar to the early phase of acute pulmonary
      distress syndrome. Cardiopulmonary bypass resulted in an increase in pulmonary
      elastance without changes in resistance. This experimental model is suitable for
      studies concerning the mechanisms of acute lung injury induced by cardiopulmonary
      bypass.

PMID- 11531027
TI  - Regional changes in constitutive nitric oxide synthase and the hemodynamic
      consequences of its inhibition in lipopolysaccharide-treated pigs.
AB  - The role of constitutive nitric oxide synthases (cNOS) in sepsis remains
      controversial. Part of the problem is that many of the studies have been
      performed in rats, which respond differently than larger animals. Our objective,
      therefore, was to determine whether cNOS, i.e. ecNOS (NOS-3) and nNOS (NOS-1) are
      still active in vessels of pigs treated with lipopolysaccharide (LPS) from
      Escherichia coli. We also characterized the dose-response relationship of the NOS
      inhibitor N(G)-nitro-L-arginine-methyl-ester (L-NAME) in the arterial, venous,
      and pulmonary circuits as a reflection of NO production. We anesthetized and
      ventilated 14 pigs, which were instrumented for hemodynamic measurements. We
      measured mean circulatory filling pressure and resistance to venous return by
      transiently arresting the circulation with a balloon in the right atrium. Animals
      were given 20 microg/kg of LPS (n = 8) or saline (n = 6) over 2 h. They were then
      given progressively increasing doses of L-NAME (0.5 to 16 microg/kg). We injected
      20 microg boluses of norepinephrine at baseline, after 2 h, and after 0.5, 4, and
      16 microg of L-NAME to test the pressor response. Tissue was obtained from six
      control animals followed for 2 h, eight animals treated with LPS for 2 h and then
      sacrificed, and four animals treated for 2 h and sacrificed after 2 more h.
      Cardiac output did not change, and the systemic vascular resistance fell in LPS
      animals. By Western analysis, ecNOS was increased in LPS animals at 2 and 4 h in
      the aorta and vena cava, and this was paralleled by changes in nNOS in the vena
      cava. In contrast, ecNOS decreased in the pulmonary artery and nNOS did not
      change. Calcium-dependent NOS activity increased with LPS in the aorta and vena
      cava but decreased in pulmonary artery at 4 h. The dose-response relationships to
      L-NAME for systemic vascular resistance, resistance to venous return, and cardiac
      output were shifted to the left after LPS in support of increased sensitivity
      supporting increased NO. The pressor response to norepinephrine was depressed
      after LPS and was partially restored with 4 mg/kg of L-NAME, but this dose
      produced 90% of the fall in cardiac output. In conclusion, in contrast to rats,
      cNOS activity is present in the systemic vessels of LPS-treated pigs and could
      play a role in the pathophysiology of sepsis.

PMID- 11531026
TI  - Differential activation of coronary and pulmonary endothelial cells by thermal
      injury.
AB  - Remote organ dysfunction during resuscitation of severe thermal injury is
      characterized by early, transient pulmonary insufficiency and cardiac contractile
      dysfunction. Thermal injury is typified by profound systemic alterations of
      endothelial immunological, vasoactive, and barrier functions. The unique location
      of this ubiquitous, fragile monolayer makes it vulnerable to circulating serum
      factors created at remote cutaneous wounds. We examined endothelial "activation"
      in 2 distinct cell types, human coronary and pulmonary endothelial cells (EC),
      after severe thermal injury. By using human serum isolated at specific times
      after thermal injury ("early" [2 h post-burn] or "late" [26 h post-burn]), the
      endothelial release of vasoactive mediators, ICAM-1 expression, and monolayer
      permeability were assessed in vitro. Early burn serum enhanced coronary EC
      vasoconstrictor (ET-1) release and ICAM expression, inhibited vasodilator (PGI2)
      release, but had no effect on permeability. Conversely, under similar conditions,
      pulmonary EC PGI2 release and permeability were enhanced, ET-1 release was
      diminished, but ICAM was unaffected. Late burn serum enhanced vasodilator (NO)
      release and permeability to albumin in both coronary and pulmonary EC, whereas ET
      1 release was inhibited. Under these conditions, only pulmonary ICAM expression
      was significantly enhanced. These data suggest that human endothelium isolated
      from divergent vascular beds are activated by burn injury in a unique manner for
      time post-burn and vascular site of cell origin.

PMID- 11531028
TI  - A pig hemorrhagic shock model: oxygen debt and metabolic acidemia as indicators
      of severity.
AB  - "Uncontrolled bleeding," "a controlled prefixed bleeding volume," or "controlled
      decrements in blood pressure" are traditional models of experimental hemorrhagic
      shock. They are influenced by compensatory mechanisms and do not adequately
      reflect the severity of the cellular insult as a major target for therapeutic
      strategies. The aim of this study was to develop an animal model that uses oxygen
      debt (OD) and metabolic acidemia as indicators of hemorrhage severity. Twenty
      five female pigs (mean weight: 23.8 kg) were anesthesized and randomized to 1 of
      5 groups of increasing OD (<50 through >120 mL/kg). The predetermined OD was
      accrued by hemorrhage uniformly over 60 min and followed by retransfusion. The
      animals were allowed to recover under anesthesia for 200 min and were then
      observed for 3 days. The extent of metabolic derangements were quantified by
      arterial base excess (BE) and plasma lactate (LAC) measurements. OD, BE, and LAC
      were shown to be superior as predictors of outcome in comparison with traditional
      variables ("bleeding volume," "blood pressure," "cardiac output") in correlation
      and regression. Of the analyzed predictors of outcome, BE and LAC showed the
      highest correlation to levels of OD (r = -0.78, 0.8 respectively; P < 0.0001),
      and regression models were developed. The LD50 for OD was 95.0 mL/kg, for BE 
      15.3 mmol/L and for LAC 7.7 mmol/L. By using the developed regression models, it
      is possible to estimate accurately the actual level of OD from BE and LAC values
      obtained during hemorrhagic shock. OD, BE, and LAC appear to be optimal
      indicators of severity for a pig hemorrhagic shock model.

PMID- 11531030
TI  - Energy cost of riding bicycles with shock absorption systems on a flat surface.
AB  - Bike shock absorption systems reduce the energy variation induced by terrain
      irregularities, leading to a greater comfort. However, they may also induce an
      increase in energy expenditure for the rider. More specifically, cross-country
      racers claim that rear shock absorption systems generate significant energy loss.
      The energy losses caused by such systems may be divided in terrain-induced or
      rider-induced. This study aims at evaluating the rider-induced energy loss of
      modern suspended bicycles riding on a flat surface. Twelve experienced
      competitive racers underwent three multistage gradational tests (50 to 250 W) on
      a cross-country bicycle mounted on an electromagnetically braked cycle ergometer.
      Three different tests were performed on a fully suspended bike, front suspended
      and non-suspended bicycle, respectively. The suspension mode has no significant
      effect on VO2. The relative difference of VO2 between the front-suspended or full
      suspended bike and the rigid bike reaches a non significant maximum of only 3%.
      The claims of many competitors who still prefer front shock absorption systems
      could be related to a possible significant energy loss that could be present at
      powers superior to 250 W or when they stand on the pedals. It could also be
      generated by terrain-induced energy loss.

PMID- 11531029
TI  - Redistribution of pulmonary blood flow during hypoxic exercise.
AB  - Pulmonary blood flow (PBF) distribution was studied at rest and during exercise
      in rats acclimatized to chronic hypoxia (barometric pressure [PB] 370 Torr for 3
      weeks, A rats) and non-acclimatized (NA) littermates. Both A and NA rats
      exercised in hypoxia (inspired O2 pressure [PIO2] approximately 70 Torr) or in
      normoxia (PlO2 approximately 145 Torr). PBF distribution was determined using
      fluorescent-labeled microspheres injected into the right atrium. The lungs were
      cut into 28 samples to determine relative scatter of specific PBF ([sample
      fluorescence intensity/sample dry weight)/(total lung fluorescence
      intensity/total lung dry weight]). Exercise produced redistribution of PBF both
      in NA and A rats, and this effect was larger in hypoxia than in normoxia, with
      minimal redistribution occurring during normoxic exercise in NA rats. The pattern
      of distribution varies considerably among individual animals. As a result of
      distribution, the previous high flow areas would be overperfused during hypoxic
      exercise in some rats. The results support the concept that hypoxic pulmonary
      vasoconstriction is not uniform and suggest that the combination of hypoxia and
      exercise may lead to overperfusion and capillary leak in some individuals.

PMID- 11531031
TI  - Hemodynamic responses to increasing cycle cadence in 11-year old boys: role of
      the skeletal muscle pump.
AB  - Previous studies in adults have indicated a rise in the metabolic cost of
      increasing cycling cadence at constant work rates. This study examined the
      metabolic and cardiovascular responses to pedaling rates of 41, 63, and 83 rpm at
      both zero-load and 50-watts load in 12 prepubertal boys. Increasing cadence from
      41 to 83 rpm produced a 52.9% and 23.1% rise in gross energy expenditure in the
      two work conditions, respectively, despite the constant external work rate. This
      augmented energy expenditure was accounted for entirely by internal work, as no
      changes in work metabolic cost (difference between loaded and unloaded cycling)
      were observed as cadence increased. The rise in energy expenditure with higher
      pedaling rate during the zero load and 50 watt conditions was accompanied by
      increases in both heart rate and stroke volume. Arterial venous oxygen difference
      did not change with increased cadence but was significantly higher with loaded
      cycling, suggesting that skeletal muscle pump effectiveness is negatively
      influenced by increased load but not by increased pedaling rate.

PMID- 11531032
TI  - Impotence and genital numbness in cyclists.
AB  - Cyclists often complain of genital numbness and even of impotence. The purpose of
      this study was to determine if perineal compression during cycling causes changes
      in the penile blood supply, impotence and penile numbness. Forty healthy athletic
      men with a mean age of 30 +/- 5.3 years took part in the study. Transcutaneous
      penile oxygen pressure was obtained using a device consisting of a modified Clark
      pO2 electrode, attached to the glans of the penis. All men were measured in a
      standing position before, in a seated and standing position during and in a
      standing position after cycling. Additionally, a detailed interview was carried
      out with each man. The penile blood supply--which correlates with the
      transcutaneous PO2 at the glans-- decreased significantly in over 70% of the test
      subjects during cycling in a seated position. Cycling in a standing position did
      not show any alteration in the penile blood supply as compared to the values
      measured before exercising. Numbness of the genital region was reported by 61% of
      the cyclists. 19% of cyclists who had a weekly training distance of more than 400
      km complained of erectile dysfunction. The results of the present study showed
      that there is a deficiency in penile perfusion due to perineal arterial
      compression. This could be a reason for penile numbness and impotence in long
      distance cyclists. Therefore, we suggest restricting the training distance, and
      taking sufficient pauses during the course of prolonged and vigorous bicycle
      riding, in order to avoid penile numbness and impotence.

PMID- 11531033
TI  - Footwear affects the behavior of low back muscles when jogging.
AB  - Use of modified shoes and insole materials has been widely advocated to treat low
      back symptoms from running impacts, although considerable uncertainty remains
      regarding the effects of these devices on the rate of shock transmission to the
      spine. This study investigated the effects of shoes and insole materials on a)
      the rate of shock transmission to the spine, b) the temporal response of spinal
      musculature to impact loading, and c) the time interval between peak lumbar
      acceleration and peak lumbar muscle response. It was hypothesised that shoes and
      inserts a) decrease the rate of shock transmission, b) decrease the low back
      muscle response time, and c) shorten the time interval between peak lumbar
      acceleration and peak lumbar muscle response. Twelve healthy subjects were tested
      while jogging barefoot (unshod) or wearing identical athletic shoes (shod).
      Either no material, semi-rigid (34 Shore A), or soft (9.5 Shore A) insole
      material covered the force plate in the barefoot conditions and was placed as
      insole when running shod. Ground reaction forces, acceleration at the third
      lumbar level, and erector spinae myoelectric activity were recorded
      simultaneously. The rate of shock transmission to the spine was greater (p <
      0.0003) unshod (acceleration rate: Means +/- SD 127.35 +/- 87.23 g/s) than shod
      (49.84 +/- 33.98 g/s). The temporal response of spinal musculature following heel
      strike was significantly shorter (p < 0.023) unshod (0.038 +/- 0.021 s) than shod
      (0.047 +/- 0.036 s). The latency between acceleration peak (maximal external
      force) and muscle response peak (maximal internal force) was significantly (p <
      0.021) longer unshod (0.0137 +/- 0.022s) than shod (0.004 +/- 0.040 s). These
      results suggest that one of the benefits of running shoes and insoles is improved
      temporal synchronization between potentially destabilizing external forces and
      stabilizing internal forces around the lumbar spine.

PMID- 11531034
TI  - Comparing sports injuries in men and women.
AB  - OBJECTIVE: To compare the pattern of injury between men and women in seven
      collegiate sports to determine if gender-specific factors exist which could be
      modified to reduce the risk of injury to female athletes. DESIGN: Retrospective
      cohort study of injury reports compiled by certified athletic trainers between
      Fall 1980 and Spring 1995. SETTING: An NCAA division III College. PARTICIPANTS:
      Eighteen to 22 year-old male and female college athletes competing in seven like
      sports (basketball, cross-country running, soccer, swimming, tennis, track and
      water polo) at the intercollegiate level, playing similar number of contests and
      using the same facilities. MAIN OUTCOME MEASURES: Analyses of injury patterns,
      classified by sport and anatomic location, for men and women in seven like
      sports. RESULTS: A total of 3,767 participants were included in the study, with
      1874 sports-related injuries reported among the men and women's teams. Of these
      injuries, 856 (45.7%) were sustained by female and 1018 (54.3%) by male athletes.
      Overall, no statistically significant gender difference was found for injuries
      per 100 participant-years (52.5 for female athlete versus 47.7 for males). A
      statistically significant gender difference in injury incidence (p < 0.001) was
      seen for two sports: swimming and water polo. Female swimmers reported more
      back/neck, shoulder, hip, knee and foot injuries: and female water polo players
      reported more shoulder injuries. When evaluating all sports concurrently, female
      athletes reported a higher rate of hip, lower-leg and shoulder injuries, while
      male athletes reported a higher rate of thigh injuries. CONCLUSION: Except for
      some minor gender differences in total injuries for two sports and several
      differences in total injuries by anatomic location, our data suggest very little
      difference in the pattern of injury between men and women competing in comparable
      sports. The increased rate of shoulder injury among female swimmers probably
      resulted from the more rigorous training philosophy of their coach. Thus, no
      gender-specific recommendations can be suggested for decreasing the incidence of
      injury to female athletes competing in these sports.

PMID- 11531035
TI  - Administration of 100% oxygen in diving accidents--an evaluation of four
      emergency oxygen devices.
AB  - As the use of oxygen enhances the resorption of gas bubbles in decompression
      illness, it is recommended and generally accepted that the inspired oxygen
      concentration in emergency treatment of diving accidents has to be as close to
      100% as possible. Therefore, several emergency oxygen devices are offered to the
      diving community but only with little data in literature on the efficacy of these
      devices. We tested four emergency oxygen devices with respect to efficacy of
      oxygen supply and breathing comfort at rest. Nine blinded volunteers had to
      breathe from the four systems with face mask and mouthpiece as well. Gases were
      measured with mass spectrometry during a 3 min interval from a capillary port
      close to the subject. The results showed that none of the systems was able to
      deliver 100% oxygen all the time, but in three systems inspiratory oxygen values
      were achieved, although in one system the nitrogen wash-out was slowed due to air
      contamination during inspiration. The fourth tested system frequently supplied
      the subjects simply with air while breathing at rest. We conclude from our study
      that it is difficult to achieve oxygen levels close to 100% in practice. Even in
      a perfectly working system, the interface between device and subject is a source
      of entrained air, especially when oxygen breathing has to be performed over a
      longer period of time. In addition, two of four systems had conceptional problems
      to supply the subjects with pure O2 during inspiration. None of the tested
      systems was perfectly designed to serve in such emergencies.

PMID- 11531036
TI  - Efficacy and tolerability of escin/diethylamine salicylate combination gels in
      patients with blunt injuries of the extremities.
AB  - The aim of this confirmative, monocentre, double-blind, controlled clinical trial
      was to investigate whether different escin combinations show differences in
      comparison to placebo with regard to pain reactions in the topical treatment of
      sports injuries. A total of 126 patients with blunt injuries of the extremities
      were randomly allocated to four parallel groups: Reparil-Gel N (n = 32), Reparil
      Gel (n = 31), Reparil-Sportgel (n = 32) and a placebo gel (n = 31). All patients
      were evaluated for efficacy (intention to treat) and tolerability. A per-protocol
      analysis was also carried out, in which 12 of the 126 patients were excluded due
      to protocol violations. The intention-to-treat and per-protocol analyses produced
      similar results. The patients had suffered contusions while participating in
      soccer, hockey, karate, tae-kwon-do, handball, American football, rugby or
      tennis. The measured variable was the pressure required at the centre of the
      lesion to elicit the first pain reaction (tenderness reaction) at measuring time
      0 (baseline) and then 1, 2, 3, 4, 6 and 24 h after the injury. The primary
      variable was the area under the curve (AUC) for tenderness over a six-hour
      period. The mean AUC differed significantly in the four groups (Kruskal-Wallis
      test p = 0.0001). Then six pairwise comparisons of two treatment groups each were
      carried out using the Mann-Whitney test. To control the multiple significance
      level of 5%, the adjusted p-values according to the Holm-Shaffer method were used
      in these tests. The three active gels were significantly superior to the placebo
      gel (Mann-Whitney test, p = 0.0004 in each case) in terms of the AUC. There were
      no significant differences between the active test substances in terms of the
      primary variable. The intensity of the pain was also measured on a visual
      analogue scale (VAS). The pain diminished more rapidly with the Reparil gels than
      with the placebo. The tolerability of all test substances was good. No adverse
      events were observed in any of the 126 patients. Escin combination gels are more
      effective than a placebo and are also well tolerated. Therefore, they can be
      recommended for the treatment of blunt injuries caused during sports and leisure
      activities.

PMID- 11531037
TI  - Reproducibility of cardiac output measurements by Doppler echocardiography in
      prepubertal children and adults.
AB  - The aim of this study was to examine reproducibility of stroke volume and cardiac
      output measurements by Doppler echocardiography during submaximal and maximal
      exercise in adults and children. Fourteen healthy children (8 girls and 6 boys
      aged 10.9 +/- 0.9yr) and eleven healthy young adults (1 female and 10 males aged
      22.3 +/- 3.8 yr) underwent a progressive maximal upright cycle test until
      exhaustion with estimation of stroke volume and cardiac output by Doppler
      echocardiography on two separate occasions (one week apart). Maximal oxygen
      uptake and maximal heart rate were not significantly different between both tests
      in the children and adults indicating that similar exhaustive efforts were
      achieved at each test. No significant differences for mean values of stroke
      volume and cardiac output were observed at rest in the children and whatever the
      exercise intensity in the children and adults. No significant differences were
      observed between values of root mean square (precision and precision of error) in
      both groups. Thus we demonstrated that stroke volume and cardiac output values
      obtained by Doppler echocardiography at rest and during submaximal and maximal
      exercise were reproducible on test-retest measurements in children and adults.

PMID- 11531038
TI  - Effect of a 13-week aerobic training programme on the maximal power developed
      during a force-velocity test in prepubertal boys and girls.
AB  - The present study was undertaken in order to evaluate the effect of an aerobic
      training programme on the maximal power (Pmax) developed during a short-term
      exercise test in prepubertal children. Thirty-three 10-11 year old boys and girls
      were investigated: 17 (TG) participated twice a week (1 h per session) in a 13
      week running programme and 16 (CG) served as a control group. Pmax was measured
      during a force-velocity test conducted on a friction-loaded cycle ergometer. The
      force (Fopt) and velocity (Vopt) at which Pmax was obtained were determined.
      Lower limb muscle mass (LMM) was evaluated by means of dual X-ray absorptiometry.
      Following training, Pmax increased even when muscle mass change due to the growth
      process was taken into account (Pmax W: + 23 %, W x kg(-1) LMM: + 18%, p <
      0.001). The increase in Fopt was principally responsible for such an improvement
      since no alteration was noticed for Vopt after training. As for Pmax, Fopt was
      still greater following training when LMM was taken into account (p < 0.01).
      Furthermore, no changes were noticed for CG for all variables evaluated during
      the anaerobic test after the study period. Differences between TG and CG
      regarding Pmax and Fopt were obtained after training only. In conclusion this
      study highlights the effectiveness of an aerobic training programme to improve
      the maximal power during short-term exercise in prepubertal children.

PMID- 11531039
TI  - An exploratory study into the effect of exhausting bicycle exercise on endocrine
      and immune responses in post-menopausal women: relationships between vigour and
      plasma cortisol concentrations and lymphocyte proliferation following exercise.
AB  - It is well-established that bicycle exercise alters the endocrine and immune
      responses in men, but little information is available for women, especially
      middle-aged, post-menopausal women. The purpose of our study was to document the
      endocrine and immune reactivity to exhausting bicycle exercise in post-menopausal
      women, and to explore whether complaints of fatigue or low vigour are related to
      these exercise-induced responses. Thirteen healthy post-menopausal women
      participated in this study. We used a graded exercise protocol to study the
      kinetics of activation of the endocrine and immune system. We chose to examine
      hormones related to the hypothalamus-pituitary-adrenal (HPA) system such as
      adrenocorticotropin hormone (ACTH) and cortisol and hormones related to the
      pituitary such as prolactin (PRL) and growth hormone (GH). With regard to the
      immune system, we examined the natural killer (NK) cell activity and pokeweed
      (PWM)-induced lymphocyte proliferation in addition to changes in peripheral blood
      cell counts. Our results demonstrate that acute physical stress results in a
      strong release of ACTH, cortisol, GH and PRL. The bicycle test significantly
      increased the number of CD3+, CD4+, CD16/56+ (NK cells) and CD8+ cells in our
      group of post-menopausal women. Interestingly, NK activity did not increase
      significantly despite an increase in NK cell numbers. PWM-induced lymphocyte
      proliferation did not change either. In addition, our data support the hypothesis
      that low vigour in post-menopausal women interferes with the endocrine and immune
      responses to exhausting exercise. In women with complaints of low vigour we found
      lower cortisol responses and higher increments in the proliferative capacity of
      lymphocytes as compared to those with high vigour scores. NK activity was
      unrelated to exhaustive mood states. These data indicate that endocrine as well
      as immune system activity changes in response to exhausting exercise in middle
      aged, post-menopausal women. In addition, exhaustive mood states may contribute
      to cortisol responses and function of peripheral immune cells in post-menopausal
      women following exhausting exercise.

PMID- 11531040
TI  - Food restriction, performance, psychological state and lipid values in judo
      athletes.
AB  - Dietary intake, plasma lipids, lipoprotein and apolipoprotein levels,
      anthropometric measurements and anaerobic performance were studied in eleven judo
      athletes during a period of weight maintenance (T1) and after a 7d food
      restriction (T2). Dietary data were collected using a 7-day diet record. Nutrient
      analysis indicated that these athletes followed a low carbohydrate diet whatever
      the period of the investigation. Moreover, mean micronutrient intakes were below
      the French recommendations. Food restriction resulted in significant decreases in
      body weight. In addition, it had significant influence on triglyceride and free
      fatty acid, although glycerol, total cholesterol, LDL-C, HDL-C, apolipoprotein A
      1 and B did not alter. Left arm strength and 30 s jumping test decreased
      significantly. The 7 s jumping test was not affected by the food restriction.
      Regardless of psychological parameters, tension, anger, fatigue and confusion
      were significantly elevated from T1 to T2; vigor was significantly lower. The
      data indicated that a 7-day food restriction adversely affects the physiology and
      psychology of judo athletes and impairs physical performance, possibly due to
      inadequate carbohydrate and micronutrients.

PMID- 11531041
TI  - Training practices and overtraining syndrome in Swedish age-group athletes.
AB  - Heavy training in combination with inadequate recovery actions can result in the
      overtraining/staleness syndrome and burnout. Even young and aspiring elite
      athletes develop staleness. The aim was therefore to determine the incidence and
      nature of staleness, and its association with training behavior and psychosocial
      stressors in young elite athletes. A sample of 272 individuals from 16 sports
      completed questionnaires on training, staleness, and psychosocial stress and 37%
      reported being stale at least once. The incidence rate was higher for individual
      sports (48%) compared with team (30%) and less physically demanding sports (18%).
      Stale athletes reported greater perceptual changes and negatively elevated mood
      scores in comparison to healthy athletes. Staleness was distinguished from
      burnout on the basis of motivational consequences; 41 % of the athletes lost
      their motivation for training, which in turn indicates a state of burnout.
      Further, 35 % of the athletes reported low satisfaction with time spent on
      important relationships, 29% rated the relationship with their coach as ranging
      from very, very bad to only moderately good. The results indicate that staleness
      is a widespread problem among young athletes in a variety of sports, and is not
      solely related to physical training, but also to non-training stressors.

PMID- 11531042
TI  - Harm reduction: closing the distance.

PMID- 11531043
TI  - Total hip replacement: need far exceeds supply.

PMID- 11531044
TI  - Cisapride and the Vanessa Young inquest.

PMID- 11531045
TI  - The accidental cell phone  user.

PMID- 11531046
TI  - Corticosteroids and avascular necrosis of the femoral head.

PMID- 11531047
TI  - The ethics of anonymous chart reviews.

PMID- 11531048
TI  - Unsafe injection practices in a cohort of injection drug users in Vancouver:
      could safer injecting rooms help?
AB  - BACKGROUND: In several European countries safer injecting rooms have reduced the
      public disorder and health-related problems of injection drug use. We explored
      factors associated with needle-sharing practices that could potentially be
      alleviated by the availability of safer injecting rooms in Canada. METHODS: The
      Vancouver Injection Drug User Study is a prospective cohort study of injection
      drug users (IDUs) that began in 1996. The analyses reported here were restricted
      to the 776 participants who reported actively injecting drugs in the 6 months
      before the most recent follow-up visit, during the period January 1999 to October
      2000. Needle sharing was defined as either borrowing or lending a used needle in
      the 6-month period before the interview. RESULTS: Overall, 214 (27.6%) of the
      participants reported sharing needles during the 6 months before follow-up; 106
      (13.7%) injected drugs in public, and 581 (74.9%) reported injecting alone at
      least once. Variables independently associated with needle sharing in a
      multivariate analysis included difficulty getting sterile needles (adjusted odds
      ratio [OR] 2.7, 95% confidence interval [CI] 1.8-4.1), requiring help to inject
      drugs (adjusted OR 2.0, 95% CI 1.4-2.8), needle reuse (adjusted OR 1.8, 95% CI
      1.3-2.6), frequent cocaine injection (adjusted OR 1.6, 95% CI 1.1-2.3) and
      frequent heroin injection (adjusted OR 1.5, 95% CI 1.04-2.1). Conversely, HIV
      positive participants were less likely to share needles (adjusted OR 0.5, 95% CI
      0.4-0.8), although 20.2% of the HIV-positive IDUs still reported sharing needles.
      INTERPRETATION: Despite the availability of a large needle-exchange program and
      targeted law enforcement efforts in Vancouver, needle sharing remains an
      alarmingly common practice in our cohort. We identified a number of risk
      behaviours--difficulty getting sterile needles, needle sharing and reuse,
      injection of drugs in public and injecting alone (one of the main contributing
      causes of overdose)--that may be alleviated by the establishment of supervised
      safer injecting rooms.

PMID- 11531049
TI  - Hospital utilization and costs in a cohort of injection drug users.
AB  - BACKGROUND: Many injection drug users (IDUs) seek care at emergency departments
      and some require hospital admission because of late presentation in the course of
      their illness. We determined the predictors of frequent emergency department
      visits and hospital admissions among community-based IDUs and estimated the
      incremental hospital utilization costs incurred by IDUs with early HIV infection
      relative to costs incurred by HIV-negative IDUs. METHODS: The Vancouver Injection
      Drug User Study (VIDUS) is a prospective cohort study involving IDUs that began
      in 1996. Our analyses were restricted to the 598 participants who gave informed
      consent for our study. We used the participants' responses to the baseline VIDUS
      questionnaire and, from medical records at St. Paul's Hospital, Vancouver, we
      collected detailed information about the frequency of emergency department
      visits, hospital admissions and the primary diagnosis for all visits or hospital
      stays between May 1, 1996, and Aug. 31, 1999. The incremental difference in
      hospital utilization costs by HIV status was estimated, based on 105 admissions
      in a subgroup of 64 participants. RESULTS: A total of 440 (73.6%) of the 598 IDUs
      made 2763 visits to the emergency department at St. Paul's Hospital during the
      study period. Of these 440, 265 (160.2%) made frequent visits (3 or more). The
      following factors were associated with frequent use: HIV-positive status
      (seroprevalent: adjusted odds ratio [OR] 1.7, 95% confidence interval [CI] 1.2
      2.6; seroconverted during study period: adjusted OR 3.0, 95% CI 1.6-5.7); more
      than 4 injections daily (adjusted OR 1.5, 95% CI 1.1-2.1); cocaine use more
      frequent than use of other drugs (adjusted OR 2.0, 95% CI 1.2-3.6); and unstable
      housing (adjusted OR 1.5, 95% CI 1.1-2.2). During the study period 210 of the
      participants were admitted to hospital 495 times; 118 (56.2%) of them were
      admitted frequently (2 or more admissions). The 2 most common reasons for
      admission were pneumonia (132 admissions among 79 patients) and soft-tissue
      infections (cellulitis and skin abscess) (90 admissions among 59 patients). The
      following factors were independently associated with frequent hospital
      admissions: HIV-positive status (seroprevalent: adjusted OR 5.4, 95% CI 3.4-8.6;
      seroconverted during study period: adjusted OR 2.9, 95% CI 1.4-6.0); and female
      sex (adjusted OR 1.8, 95% CI 1.1-3.1). The incremental hospital utilization costs
      incurred by HIV-positive IDUs relative to the costs incurred by HIV-negative IDUs
      were $1752 per year. INTERPRETATION: Hospital utilization was significantly
      higher among community-based IDUs with early HIV disease than among those who
      were HIV negative. Much of the hospital use was related to complications of
      injection drug use and may be reduced with the establishment of programs that
      integrate harm reduction strategies with primary care and addiction treatment.

PMID- 11531050
TI  - A snapshot of waiting times for cancer surgery provided by surgeons affiliated
      with regional cancer centres in Ontario.
AB  - BACKGROUND: There is evidence that delays in treatment result in increased
      psychosocial morbidity for patients diagnosed with cancer. We evaluated waiting
      times for care among cancer patients treated by surgeons affiliated with regional
      cancer centres in Ontario. METHODS: Dates for 5 key events related to the
      surgical management of a patient with cancer were collected by a convenience
      sample of surgeons who treat breast, gynecologic, colorectal, head and neck,
      thoracic and urologic cancers. The key events were initial referral, first
      surgical visit, main treatment decision, major surgery and receipt of
      postoperative pathology report. The surgeons were also asked to judge the
      appropriateness of the waiting times for the intervals studied and to identify
      factors associated with inappropriate delays. RESULTS: A total of 62 surgeons
      affiliated with 8 regional cancer centres participated; data were collected for
      1456 patients who underwent assessment and whose surgical visit occurred between
      Jan. 31 and May 31, 2000. The median waiting time from referral to first visit
      was 11.0 days, from first visit to treatment decision 0.0 days, from treatment
      decision to surgery 20.0 days and from surgery to receipt of the pathology report
      8.0 days. The median waiting times for the 2 summary intervals (referral to
      surgery and referral to receipt of the pathology report) were 37.0 and 48.0 days
      respectively. The waiting times varied by cancer type; for example, the median
      time from referral to surgery varied from 29.0 days for colorectal cancers to
      64.0 days for urologic cancers. The same interval varied from 19.0 to 43.0 days
      by treatment centre. The waiting times did not vary substantially by patient age.
      The surgeons judged that 344 (37.2%) of the 925 patients with dates for the
      referral-to-surgery interval had inappropriately long waiting times. They
      indicated that contributing factors to these inappropriate waits were shortage of
      operating room time (in 181 cases), lack of other resources such as diagnostic
      tests or allied health personnel (in 156) and patient preference or circumstance
      (in 28) (factors were not mutually exclusive). INTERPRETATION: Many of the
      patients with cancer seen by surgeons affiliated with regional cancer centres in
      Ontario may be experiencing significant delays in the assessment and treatment of
      their cancer.

PMID- 11531051
TI  - Impact of waiting time on the quality of life of patients awaiting coronary
      artery bypass grafting.
AB  - BACKGROUND: A lack of resources has created waiting lists for many elective
      surgical procedures within Canada's universal health care system. Coronary artery
      bypass grafting (CABG) for the treatment of atherosclerotic ischemic heart
      disease is one of these affected surgical procedures. We studied the impact of
      waiting times on the quality of life of patients awaiting CABG. METHODS: A
      prospective cohort of 266 patients from 3 hospitals in Montreal was used.
      Patients who gave informed consent were followed from the time they were
      registered for CABG until 6 months after surgery; recruitment began in November
      1993, and the last follow-up was completed in July 1995. Patient groups were
      classified according to the duration of the wait for CABG (< or = 97 days or > 97
      days). We measured the following outcomes: quality of life (using the Medical
      Outcomes Study 36-item Short Form [SF-36]), incidence of chest pain (using the
      New York Heart Association angina classification), frequency of symptoms (using
      the Cardiac Symptom Inventory) and rates of complications and death before and
      after surgery. RESULTS: There were no differences in quality of life at baseline
      between the 2 groups. Immediately before surgery, compared with patients who
      waited 97 days or less, those who waited longer had significantly reduced
      physical functioning (change from baseline SF-36 score 0 v. -4 respectively, p =
      0.001), vitality (change from baseline score -0.1 v. -1.3, p = 0.01), social
      functioning (change from baseline score 0.4 v. -0.4, p = 0.03) and general health
      (change from baseline score 1.1 v. -1.7, p = 0.001). At 6 months after surgery,
      compared with patients who waited 97 days or less for CABG, those who waited
      longer had reduced physical functioning (change from baseline SF-36 score 4.0 v. 
      0.1 respectively, p = 0.001), physical role (change from baseline score 0.8 v.
      0.0, p = 0.001), vitality (change from baseline score 2.2 v. 0.9, p = 0.001),
      mental health (change from baseline score 1.2 v. 0.0, p = 0.001) and general
      health (change from baseline score 1.8 v. -0.3, p = 0.001). The incidence of
      postoperative adverse events was significantly greater among the patients with
      longer waits for CABG than among those with shorter waits (32 v. 14 events
      respectively, p = 0.005). Longer waits before CABG were associated with an
      increased likelihood of not returning to work after surgery (p = 0.08): 10 (53%)
      of the 19 patients with longer waiting times remained employed after CABG, as
      compared with 17 (85%) of the 20 with shorter waiting times. INTERPRETATION: The
      significant decrease in physical and social functioning, both before and after
      surgery, for patients waiting more than 3 months for CABG is an important
      observation. Longer waiting times were also associated with increased
      postoperative adverse events. By decreasing waiting times for CABG, we may
      improve patients' quality of life and decrease the psychological morbidity
      associated with CABG.

PMID- 11531052
TI  - Challenges in family practice related to informed and shared decision-making: a
      survey of preceptors of medical students.

PMID- 11531053
TI  - Safe injection facilities in Canada: is it time?

PMID- 11531054
TI  - Informed and shared decision-making: the crux of patient-centered care.

PMID- 11531055
TI  - No mere theory: Olli Miettinen's "The modern scientific physician".

PMID- 11531056
TI  - The modern scientific physician: 1. Can practice be science?

PMID- 11531057
TI  - Science misapplied: mandatory addiction screening and treatment for welfare
      recipients in Ontario.

PMID- 11531059
TI  - Direct-to-consumer prescription drug ads getting bolder.

PMID- 11531058
TI  - Transmission and postexposure management of bloodborne virus infections in the
      health care setting: where are we now?
AB  - There has been considerable debate about the need for mandatory serologic testing
      of individuals who are the source of bloodborne pathogen exposures in health care
      and other occupational settings. The transmission of hepatitis B (HBV), hepatitis
      C (HCV) and HIV between patients and health care workers (HCWs) is related to the
      frequency of exposures capable of allowing transmission, the prevalence of
      disease in the source populations, the risk of transmission given exposure to an
      infected source and the effectiveness of postexposure management. Transmission of
      HBV from patients to HCWs has been substantially reduced by vaccination and
      universal precautions. The transmission of HCV and HIV to HCWs does occur,
      although postexposure prophylaxis (PEP) is available to reduce the risk of HIV
      transmission. Transmission of bloodborne pathogens from infected HCWs to patients
      has also been documented. Policy-making concerning the mandatory postexposure
      testing of patients who may be the source of infection must weigh the relative
      infrequency of patients' refusals to be tested and the consequences for PEP
      recommendations with the ethical and legal considerations of bypassing informed
      consent and mandating testing. Mandatory postexposure testing of HCWs who are the
      source of infection will have a limited impact on reducing transmission because
      of the lack of recognition and reporting of exposures. Comprehensive approaches
      have been recommended to reduce the risk of transmission of bloodborne virus
      infections.

PMID- 11531060
TI  - Quebec clears way for use of aerial pesticides to combat West Nile virus.

PMID- 11531061
TI  - Putting patient safety on the health are agenda.

PMID- 11531062
TI  - Internet a prime venue for snake-oil sales of "health products".

PMID- 11531064
TI  - Universities becoming a breeding ground for businesses.

PMID- 11531063
TI  - Almost 1 in 2 Canadians says health system needs major surgery.

PMID- 11531065
TI  - Accidental falls from heights.

PMID- 11531066
TI  - The extracellular matrix of muscle--implications for manipulation of the
      craniofacial musculature.
AB  - Successful adaptation of craniofacial skeletal muscle is dependent upon the
      connective tissue component of the muscle. This is exemplified by procedures such
      as distraction histo/osteogenesis. The mechanisms underlying remodelling of
      intramuscular connective tissue are complex and multifactorial and involve
      extracellular matrix (ECM) molecules, receptors for the ECM (integrins) and
      enzymes that remodel the ECM (MMPs). This review discusses the current state of
      knowledge and clinical implications of connective tissue biology as applied to
      craniofacial skeletal muscle.

PMID- 11531068
TI  - Etiologic factors influencing the prevalence of demarcated opacities in permanent
      first molars in a group of Swedish children.
AB  - The aim of this study was to determine possible etiological factors for a
      developmental enamel defect, i.e. demarcated opacities, affecting the permanent
      first molars. A questionnaire about possible etiological factors of enamel
      developmental defects was filled in by the parents of 8-yr-old children (n=516)
      prior to a dental examination of permanent teeth. Demarcated opacities of
      permanent first molars had been found in 18.4% of the children in a previous
      study of these children. Fifteen % had more than one tooth affected indicating
      systemic causation. Questions were asked about mother's health and medication
      during pregnancy, birth complications, health and medication of the child during
      the first 3 yr of life, breast-feeding, heredity, and fluoride supplements. The
      affected children, especially the boys, were reported to have had more health
      problems, in particular asthma (but only 4 cases), during the first year of life.
      Use of antibiotics was also more common among the affected children, but owing to
      a strong co-variance with health problems these factors could not be separated.
      Breast-feeding history was similar in children with and without enamel defects.
      The etiology of hypomineralized first molars is not yet fully understood, but
      based on the results of this retrospective study, health problems in infancy,
      especially respiratory diseases, seem to be involved.

PMID- 11531067
TI  - Restorations with extensive dentin/enamel-bonded ceramic coverage. A 5-year
      follow-up.
AB  - The durability of restorations with extensive dentin/enamel-bonded posterior
      partial and complete ceramic coverages were investigated. The effect of luting
      with a dual-cured and a self-cured luting agent was also studied. In 110
      patients, 182 ceramic coverages (IPS Empress) were placed. In 58 restorations,
      Syntac was used in combination with the dual-cured resin composite Variolink. In
      the other restorations luted with the chemically cured resin composite Bisfil 2B,
      25 were bonded with Gluma, 57 with Allbond 2, and 42 with Syntac. Of the 182
      ceramics, 13 (7.1%) were assessed as non-acceptable after a mean observation
      period of 4.9 yr (range 4.3 7.5 yr). The reasons for failure were fracture (5),
      lost restorations (4), secondary caries (3) and endodontic treatment (1). No
      significant differences in failure rate were seen between the two luting agents
      or between the three dentin-bonding agents. Ceramic coverages placed on non-vital
      teeth failed in 9.7% of cases (3/31) and on vital teeth in 6.6% (10/151). The
      success rate of the dentin-enamel-bonded ceramic coverages reduces the need for a
      traditional full-coverage therapy and/or post or pin(s) and core placement. The
      technique investigated showed many clinical advantages such as less destruction
      of healthy tissue, and avoidance of endodontic treatment and/or deep cervical
      placement of restoration margins.

PMID- 11531069
TI  - Factor structure of the Dental Beliefs Survey in a dental phobic population.
AB  - The aim of this study was to investigate the factor structure of the 15-item
      Dental Beliefs Survey (DBS) in a population of dental phobic patients (n=362).
      Exploratory (EFA) and confirmatory (CFA) factor analyses were used. The EFA
      indicated three factors: 'communication', 'trust', and 'fear of negative
      information'. However, the EFA further suggested a general factor with all 15
      items. By using the CFA, five factors were found based on the EFA solution and
      the original DBS dimensions. A general factor, 'social interaction distress in
      dental treatment', and four more narrow dimensions, 'communication', 'trust',
      'fear of negative information' (originally labelled 'belittlement'), and 'lack of
      control', was the most adequate result with regard to theoretical and statistical
      properties. However, some items in the factors were partly different from the
      original version of the DBS. In conclusion, the DBS attempts to measure a complex
      phenomenon with regard to patients' perceptions and attitudes to dental care.
      This study has revealed psychometric properties of the DBS in a population of
      dental phobic patients. The important finding was a general dimension, which
      suggests the use of DBS as an overall measure of dental beliefs. However, more
      research is needed in epidemiological and clinical studies with non-phobic
      individuals.

PMID- 11531071
TI  - Ultrastructural analysis of structural framework in dental plaque developing on
      synthetic carbonate apatite applied to human tooth surfaces.
AB  - This study focused on determining the structural framework by oral microbiota in
      supragingival plaque on a carbonate apatite film applied to human tooth surfaces.
      The sequential phases of plaque formation over a 3-wk period were found to be
      equivalent to those previously reported for natural tooth surfaces. Scanning
      electron microscopy of specimens prepared by vertical sectioning demonstrated the
      organization of two types of framework between certain genera of initial and
      secondary colonizers in the pre- and post-organization phases, respectively. The
      initial colonizers in the pre-organization phase were of a coccoid type, while
      colonizers in the post-organization phase were of a bacillary type. Secondary
      colonizers, filamentous cells, were common to both frameworks. Transmission
      electron microscopy using freeze-substitution and immunohistochemistry
      demonstrated two types of coaggregation, fibril- and saliva-mediated modes, among
      the plaque microbiota. Coaggregation between microbiota, which organized the
      framework, showed a tendency to occur in the fibril-mediated mode, and the
      filamentous secondary colonizers were characterized by inducing multigeneric
      coaggregation. The present findings indicate that a structural framework and
      specific cells to form this framework are essential for plaque formation.

PMID- 11531070
TI  - Periodontal tissue regeneration by combined applications of recombinant human
      osteogenic protein-1 and bone morphogenetic protein-2. A pilot study in Chacma
      baboons (Papio ursinus).
AB  - Native and recombinant human bone morphogenetic/osteogenic proteins (BMPs/ OPs)
      singly initiate bone induction in vivo. The finding of synchronous but spatially
      different BMPs/OPs expression during periodontal tissue morphogenesis suggests
      novel therapeutic approaches using morphogen combinations based on recapitulation
      of embryonic development. Twelve furcation defects prepared in the first and
      second mandibular molars of three adult baboons (Papio ursinus) were used to
      assess whether qualitative histological aspects of periodontal tissue
      regeneration could be enhanced and tissue morphogenesis modified by combined or
      single applications of recombinant hOP-1 and hBMP-2. Doses of BMPs/OPs were 100
      microg of each protein per 1 g of insoluble collagenous bone matrix as carrier.
      Approximately 200 mg of carrier matrix was used per furcation defect.
      Undecalcified sections cut for histological analysis 60 d after healing of hOP-1
      treated specimens showed substantial cementogenesis with scattered remnants of
      the collagenous carrier. hBMP-2 applied alone induced greater amounts of
      mineralized bone and osteoid when compared to hOP-1 alone or to combined
      morphogen applications. Combined applications of hOP-1 and hBMP-2 did not enhance
      alveolar bone regeneration or new attachment formation over and above the single
      applications of the morphogens. The results of this study, which is the first to
      attempt to address the structure-activity relationship amongst BMP/OP family
      members, indicate that tissue morphogenesis induced by hOP-1 and hBMP-2 is
      qualitatively different when the morphogens are applied singly, with hOP-1
      inducing substantial cementogenesis. hBMP-2 treated defects, on the other hand,
      showed limited cementum formation but a temporal enhancement of alveolar bone
      regeneration and remodelling. The demonstration of therapeutic mosaicism in
      periodontal regeneration will require extensive testing of ratios and doses of
      recombinant morphogen combinations for optimal tissue engineering in clinical
      contexts.

PMID- 11531072
TI  - Dipeptidyl-peptidase II and cathepsin B activities in amelogenesis of the rat
      incisor.
AB  - A body of published evidence suggests that a significant portion of enamel matrix
      protein synthesized by ameloblasts localises in the lysosomal-endosomal
      organelles of these enamel organ cells. Little is known regarding the lysosomal
      proteolytic activities during amelogenesis. The aims of this study were to detect
      and measure the activities of lysosomal peptidases cathepsin B (E.C. 3.4.22.1)
      and dipeptidyl-peptidase II (E.C. 3.4.14.2) in the enamel organ of the rat
      incisor and to ascertain whether rat enamel matrix proteins are degraded by these
      peptidases in vitro. Whole enamel organs were dissected from rat mandibular
      incisors. Enamel protein was also collected from the rat teeth. Analysis
      indicated that the rat incisor enamel organs contained specific activities of
      both dipeptidyl-peptidase II and cathepsin B at levels comparable with those of
      kidney which is rich in both these lysosomal peptidases. Gel electrophoresis and
      immunoblotting demonstrated that both cathepsin B and dipeptidyl-peptidase II
      were able to substantially degrade the rat enamel proteins in vitro. Based on
      these observations, we propose that lysosomal proteases have roles in
      amelogenesis in the intracellular degradation of amelogenins.

PMID- 11531073
TI  - Effects of mechanical stimulation on cell cycle duration in rat gingival
      fibroblast progenitor cells.
AB  - The aim of this investigation was to estimate cell cycle duration in rat gingival
      fibroblast progenitor cells in steady-state control and during sustained
      mechanical stimulation. Elastics (0.15 mm thick) were inserted between maxillary
      M1 and M2 of 8 wk-old male rats which were labelled with H3-TdR and killed in
      groups of 6-7 animals together with equal-sized groups of labelled control
      animals at intervals between 1-168 h. Autoradiographs of consecutive mesio-distal
      sections were used to determine grain counts for H3-TdR-labelled cells in the
      connective tissue of the gingival papilla between M2 and M3. Median cell cycle
      times (MCC) were estimated from plots of mean and median grain counts against
      time. Under steady-state conditions, MCC for heavily-labelled and lightly
      labelled paravascular cell populations and for labelled extravascular cells were
      144, 76 and 50 h, respectively. Mechanical stimulation caused a significantly
      faster rate of reduction of total grain counts relative to controls in all three
      cell populations and a decline of estimated MCC to 115, 50 and 21 h in heavily
      labelled and lightly labelled paravascular cells and labelled extravascular
      cells, respectively. These findings indicate that mechanical stimulation induces
      faster progression of gingival fibroblast progenitor cells through the cell
      cycle.

PMID- 11531074
TI  - Clinical wear performance of eight experimental dental composites over three
      years determined by two measuring methods.
AB  - The effect of matrix selection, filler composition, filler silanization, operator
      variations, and test site (dental clinic) on the wear rate of eight composites
      were evaluated. The wear was measured on replicas using both a microscopic and a
      laser scanning measuring method. The average wear rate on contact-free surfaces
      was 9.2 +/- 4.2 microm/month with the microscopic measurement and 8.5 +/- 3.7
      microm/ month with the laser scanner over the 36-month period. The urethane-based
      composites performed significantly better than those which were bisGMA-based.
      Restorations placed at one dental clinic showed significantly lower initial wear.
      There was also a significant difference between the operators that was most
      pronounced during the first 6 months. The other variable (filler composition and
      silane treatment) did not affect the wear rate significantly.

PMID- 11531075
TI  - Influence of selected components on crosslink density in polymer structures.
AB  - Bifunctional methacrylates polymerize to form crosslinked polymer structures
      which may be characterized by the quantity of remaining double bonds and by the
      crosslink density. This study investigated the influence of composition variation
      on the crosslink density of model methacrylate polymers. It was hypothesized that
      addition of a monofunctional monomer would reduce crosslink density and that
      compositions giving rise to many centers of polymer growth would result in
      increased crosslink density. Unfilled resins with varying content of BisGMA,
      TEGDMA, a monofunctional monomer, camphoroquinone, and amine were polymerized by
      visible light irradiation. After polymerization, the quantity of remaining double
      bonds and the Wallace hardness were determined. Polymer softening upon storage in
      ethanol was taken as a measure of the crosslink density. After ethanol storage,
      the relationship between hardness number and amount of monofunctional monomer
      showed a minimum. At same quantity of remaining double bonds, a high content of
      camphoroquinone compared to amine resulted in reduced softening in ethanol.
      Composition influenced not only remaining double bonds but also the crosslink
      density of the resulting polymer structures.

PMID- 11531076
TI  - Periodontitis and cardiovascular disease: an ecological fallacy?

PMID- 11531077
TI  - Common solvent toxicity: autoxidation of respiratory redox-cyclers enforced by
      membrane derangement.
AB  - Unspecific biological effects of chemically diverse solvents strikingly reveal
      the unifying motif of oxidant toxicity both in higher organisms and in aerobic
      bacteria. In a few spectacular cases, solvent metabolites with oxidant properties
      were demonstrated, which however cannot explain extrahepatic toxicity, e.g. in
      muscle and nerve cells. A common source of solvent-inducible oxidants, by
      contrast, is suggested to be located in mitochondria or, more general, in
      membranes where the respiratory chain operates. Orderly respiration depends on
      membrane integrity, which is invariably compromised by exposure to most solvents
      and many other lipophils. In rat mitochondria, toluene-induced membrane
      derangement has been directly implicated with superoxide production, resulting
      from autoxidation of the membrane-located respiratory redox-cycler
      ubisemiquinone. A related mechanism may occur in bacteria: Exposure of
      Escherichia coli to lipophils such as ethanol, tetralin, indole, chlorpromazine
      and procaine, or to heat shock, induces anti-oxidant proteins, which are reliable
      indicators of increased oxidant levels. Although many molecular details remain to
      be elucidated, this review documents that oxidant toxicity of lipophilic
      compounds is a common physiological phenomenon correlated with derangement of
      membranes where respiratory processes take place. Subjective consequences of
      acute oxidant injury are probably the hangover from alcohol and nicotine
      consumption, and the sudden death from recreational solvent abuse. Suggestions
      concerning oxidants as major contributors to ageing remain unchallenged.

PMID- 11531078
TI  - A new diprenyl coumarin and alkaloids from the bark of Zanthoxylum
      dimorphophyllum (Rutaceae).
AB  - The alkaloids chelerythrine, norchelerythrine, oxyavicine, canthine-6-one, 4,5
      dihydrocanthin-6-one, and gamma-fagarine were isolated from Zanthoxylum
      dimorphophyllum bark, together with two coumarins, scoparone and dimoxylin. This
      latter is a novel compound whose structure was elucidated on the basis of its
      spectral data.

PMID- 11531079
TI  - Melanocrocin, a polyene pigment from Melanogaster broomeianus (Basidiomycetes).
AB  - A new polyene pigment, melanocrocin, has been isolated either from fruit bodies
      or mycelial cultures of the subterranean fungus Melanogaster broomeianus. The
      structure of the pigment was determined by spectroscopic methods and chemical
      transformations. Melanocrocin is the N-acyl derivative of L-phenylalanine methyl
      ester with a polyolefinic carboxylic acid.

PMID- 11531080
TI  - A dihydroflavonol with taxonomic significance from the fern Notholaena sulphurea.
AB  - A new flavonoid, 2,3-trans-5,2'-dihydroxy-7,8-dimethoxy-dihydroflavonol-3-O
      acetate, was isolated from the farinose coating on the lower leave surface of the
      fern, Notholaena sulphurea. The 2,3-cis diastereoisomer was isolated as a co
      constituent. This novel acylated flavonoid is characteristic for the chemotype of
      N. sulphurea exhibiting yellow frond exudate. Its orrurrence underlines the
      affiliation of the species with the genus Notholaena.

PMID- 11531081
TI  - Two new sesquiterpenes from Laurus azorica.
AB  - The structures of a new eudesmane sesquiterpene, lauradiol, and a new
      secoeudesmane, azoridione, have been determined by spectroscopic methods. These
      compounds and the known sesquiterpenic alcohols, clovanediol and caryophyllenol
      II, have been isolated from the aerial parts of Laurus azorica.

PMID- 11531082
TI  - Comparative study of Tanacetum species growing in Bulgaria.
AB  - Chemical investigation of the Bulgarian species Tanacetum. parthenium, T.
      millefolium, T. achilleifolium, T. corymbosum and T. macrophyllum afforded in
      addition to 24 known sesquiterpene lactones a new 12, 8-eudesmanolide 22.
      Besides, four known highly oxigenated terpenoids and a new keto-diol 30 of the
      rare iphionane skeleton were also isolated. The structures were elucidated on the
      basis of their spectral properties. The accumulation of the different
      sesquiterpene lactones in the studied species and there classification is
      discussed.

PMID- 11531083
TI  - Iridoids from Scrophularia genus.
AB  - We report here an updated summary about iridoid composition of a series from the
      genus Scrophularia which have been investigated until now from a phytochemistry
      point of view. In addition a list is included about iridoids isolated in our
      laboratory from different plant parts of Scrophularia scorodonia L., which are
      compared with iridoids from some species of the Scrophularia genus. The present
      study may serve as a current information to researchers working on phytochemistry
      and pharmacological aspects from the Scrophularia genus and possibly to serve as
      a new starting point for future investigations.

PMID- 11531084
TI  - Flavon- and flavonolglycosides from Achillea pannonica Scheele.
AB  - The detailed investigation of a methanolic extract of aerial parts of Achillea
      pannonica SCHEELE. within a chemotaxonomic study led to the isolation of 6
      flavonoid glycosides. Besides rutin, apigenin-7-O-glucopyranoside, luteolin-7-O
      glucopyranoside, apigenin-7-O-rutinoside and acacetin-7-O-rutinoside, an unusual
      flavondiglucoside was isolated. Its structure was established by UV, 1H NMR and
      13C NMR spectroscopic methods including 2D-NMR techniques and ESI-MS as luteolin
      7,4'-O-beta-diglucoside. This substance is reported for the first time in the
      genus Achillea. Chemotaxonomic aspects are discussed briefly.

PMID- 11531085
TI  - N,N',N"-triferuloylspermidine, a new UV absorbing polyamine derivative from
      pollen of Hippeastrum x hortorum.
AB  - A new hydroxycinnamoyl polyamine derivative, N,N',N"-triferuloylspermidine (= (E)
      N-(4-aminobutyl) -3,3',3"-tris(4-hydroxy-3-methoxyphenyl)-N,N',N"- (butane-1,4
      diyl)tris [prop-2-enamide]) (1) was detected in the H2O/MeOH extract of pollen
      from Hippeastrum x hortorum. The compound was identified by on-line-coupled high
      performance liquid chromatography and atmospheric-pressure chemical-ionization
      mass spectrometry (HPLC-UV(DAD)/APCI-MS and MS/MS). The structure was proven by
      comparing the HPLC/MS data after UV-induced (E) <==> (Z) photoisomerization and
      catalytic hydrogenation of the natural compound and the synthetic reference
      compound. This is the first report of a triferuloylspermidine in nature.

PMID- 11531086
TI  - Foliar and cortex oleoresin variability of silver fir (Abies alba Mill.) in
      Albania.
AB  - Terpene composition of needle and cortical oleoresin from lateral shoots were
      analyzed by GC/MS for four Silver fir (Abies alba Mill.) populations scattered in
      natural species range in Albania. More than sixty compounds were detected in the
      needle oleoresin, which was characterized by a high content of alpha-pinene,
      camphene, beta-pinene, limonene and bornyl acetate. Three monoterpenes, alpha
      pinene, beta-pinene and limonene, and two sesquiterpenes, beta-caryophyllene and
      germacrene D, comprised the majority of cortical oleoresin. The terpene
      composition differences among the populations that led to the recognition of two
      chemotypes. The needle oleoresin from the provinces of Puka, Bulqiza and Llogara
      were characterised by high amounts of beta-pinene, camphene and alpha-pinene and
      low amounts of limonene, while that from Drenova had high amounts of beta-pinene
      and limonene. A similar pattern was found in the cortical oleoresin with the
      exception of camphene that was a minor contributor. Geographical and seasonal
      variation between the populations was, also, investigated. Multivariate analysis
      of both needle and cortical oleoresin separated Drenova (southeastern population)
      from the other sites. When both major monoterpenes and sesquiterpenes were
      considered four chemical profiles could be attributed. Based on their chemical
      profiles, the populations can be divided into two groups: Populations with high
      content of beta-pinene and alpha-pinene but a low content of limonene (Puka,
      Bulqiza and Llogara), typical of most of A. alba populations in all its
      distribution range. Population with a high content of limonene and a moderate
      content of beta-pinene and alpha-pinene (Drenova).

PMID- 11531087
TI  - Computer-aided design of novel siderophores: pyridinochelin.
AB  - Pyridinochelin, a novel tetradentate catecholate-type siderophore, has been
      designed on the basis of the active analog enterobactin and was then synthesized.
      Growth promotion tests indicate that this synthetic siderophore feeds various
      pathogenic bacteria most effectively with iron even though it lacks one
      catecholate group compared to enterobactin. The superposition of the mentioned
      siderophore structures suggests that the structure of the skeleton connecting the
      catecholate groups might be an important factor for the iron transport.

PMID- 11531088
TI  - Production of a peptidoglycolipid bioemulsifier by Pseudomonas aeruginosa grown
      on hydrocarbon.
AB  - A strain of Pseudomonas aeruginosa isolated from a polluted soil was found to
      produce an extracellular bioemulsifier when cultivated on hexadecane as sole
      carbon source. The emulsifier was precipitated with acetone and redissolved in
      sterile water. Dodecane, crude oil and kerosene were found to be good substrates
      for emulsification by the bioemulsifier. Growth and bioemulsifier production
      reached the optimal levels on the fourth and fifth day, respectively. Emulsifying
      activity was observed over a pH range of 3.5 to 10.0 with a maximum at pH 7.0.
      The activity of the bioemulsifier was heat stable up to 70 degrees C while about
      50 percent of its activity was retained at 100 degrees C. The components of the
      bioemulsifier were determined, it was found to contain carbohydrate, protein and
      lipid. The protein complex was precipitated with ammonium sulphate and
      fractionated on a Sephadex G-100. Gel electrophoresis of the bioemulsifier showed
      a single band whose molecular weight was estimated as 14,322 Da. The
      bioemulsifier was classified as a peptidoglycolipid. Certain strains of P.
      aeruginosa produce peptidoglycolipid in place of rhamnolipid.

PMID- 11531089
TI  - Enzyme-catalyzed decomposition of dibenzoyl peroxide in organic solvents.
AB  - Catalytic activity of catalase (CAT, EC 1.11.1.6), immobilized on carbon black
      NORIT and soot PM-100, with respect to decomposition of dibenzoyl peroxide (BPO)
      in non-aqueous media (acetonitrile and tetrachloromethane), was investigated with
      a quantitative UV-spectrophotometrical approach. Progress of the above reaction
      was controlled by selected kinetic parameters: the apparent Michaelis constant
      (Km(app)), the specific rate constant (k(sp)), the activation energy (Ea), the
      maximum reaction rate (Vmax), and the Arrhenius' pre-exponential factor (Z0).
      Conclusions on the tentative mechanism of the catalytic process observed were
      drawn from the calculated values of the Gibbs energy of activation (deltaG*), the
      enthalpy of activation (deltaH*), and entropy of activation (deltaS*).

PMID- 11531090
TI  - Triaziflam and Diaminotriazine derivatives affect enantioselectively multiple
      herbicide target sites.
AB  - Enantiomers of triaziflam and structurally related diaminotriazines were
      synthesized and their herbicidal mode of action was investigated. The compounds
      caused light and dark-dependent effects in multiple test systems including
      heterotrophic cleaver and photoautotrophic algal cell suspensions, the Hill
      reaction of isolated thylakoids and germinating cress seeds. Dose-response
      experiments revealed that the (S)-enantiomers of the compounds preferentially
      inhibited photosystem II electron transport (PET) and algae growth with
      efficacies similar to that of the herbicide atrazine. In contrast, the (R)
      enantiomers of the diaminotriazines were up to 100 times more potent inhibitors
      of growth in cleaver cell suspensions and cress seedlings in the dark than the
      (S)-enantiomers. The most active compound, the (R)-enantiomer of triaziflam,
      inhibited shoot and root elongation of cress and maize seedlings at
      concentrations below 1 microM. The meristematic root tips swelled into a club
      shape which is typical for the action of mitotic disrupter herbicides and
      cellulose biosynthesis inhibitors. Microscopic examination using histochemical
      techniques revealed that triaziflam (R)-enantiomer blocks cell division in maize
      root tips 4 h after treatment. The chromosomes proceeded to a condensed state of
      prometaphase but were unable to progress further in the mitotic cycle. Disruption
      of mitosis was accompanied by a loss of spindle and phragmoplast micotubule
      arrays. Concomitantly, cortical microtubules decreased which could lead to
      isodiametric cell growth and consequently to root swelling. In addition, a
      decline in cellulose deposition in cell walls was found 24 h after treatment.
      Compared to the (R)-form, triaziflam (S)-enantiomer was clearly less active. The
      results suggest that triaziflam and related diaminotriazines affect
      enantioselectively multiple sites of action which include PET inhibitory
      activity, mitotic disruption by inhibiting microtubule formation and inhibition
      of cellulose synthesis.

PMID- 11531091
TI  - Limonoids from the endemic Brazilian species Raulinoa echinata.
AB  - Phytochemical survey of stems and leaves of the South Brazilian endemic Raulinoa
      echinata Cowan, Rutaceae led to the isolation of five limonoid derivatives: the
      widespread limonin, limonexic acid, kihadalactone B, a methoxylated limonexic
      acid derivative and a degraded limonoid structurally related to fraxinellone. The
      two latter compounds have been isolated for the first time. These compounds
      displayed weak inhibitory activity when assayed in vitro against trypomastigote
      forms of Trypanosoma cruzi. In this paper, the isolation, structure elucidation
      and bioactivity of these compounds are reported.

PMID- 11531092
TI  - The repellence of Aristolochia aff. orbicularis roots against the corn borer
      Sitophilus zeamais.
AB  - The repellence of Aristolochia aff. orbicularis root, a native of Xochipala,
      Guerrero, Mexico, to the corn borer Sitophilus zeamais (Coleoptera) was
      investigated. The essential oil was isolated from the aromatic root and its
      repellent effect was assessed. About 40 components of the oil were identified
      using gas chromatography-mass spectrometry and other spectroscopic methods. The
      repellence of the roots, the oil and the chromatography fractions were also
      evaluated. Some fractions had a higher repellence than the total oil.

PMID- 11531093
TI  - Bradyrhizobium japonicum mutants defective in cyclic beta-glucan synthesis show
      enhanced sensitivity to plant defense responses.
AB  - Susceptibility of the nitrogen-fixing soybean symbiont Bradyrhizobium japonicum
      to inducible plant defense metabolites such as phytoalexin and H2O2, was
      investigated. On the wild-type strain USDA 110 the soybean phytoalexin,
      glyceollin, showed bacteriostatic activity. Viable bacteria isolated from intact
      nodules were adapted to glyceollin. H2O2 in physiological concentrations did not
      affect wild-type bacteria. B. japonicum mutants defective in the biosynthesis of
      cyclic beta-(1-->3)-(1-->6)-glucans showed higher susceptibility to both
      phytoalexin and H2O2.

PMID- 11531094
TI  - Differential changes in the steady state levels of thylakoid membrane proteins
      during senescence in Cucumis sativus cotyledons.
AB  - Chloroplast structure and function is known to alter during foliar senescence.
      Besides, the alterations in the structural organisation of thylakoid membranes
      changes in the steady state levels of thylakoid membrane proteins occur due to
      leaf ageing. We monitored temporal changes in some of the specific proteins of
      thylakoid membrane protein complexes by western blotting in the Cucumis sativus
      cotyledons as a function of the cotyledon age. We observed that the levels of D1
      and D2 proteins of photosystem II started declining at the early stages of
      senescence of Cucumis cotyledons and continued to decline with the progress of
      cotyledon age. Similarly the level of Cyt f of Cyt b6/f complex declined rapidly
      with progress of senescence in these cotyledons. The reaction centre proteins of
      photosystem I were relatively found to be more stable than that of photosystem II
      reaction centre proteins reflecting possibly the disorganisation of photosystem
      II prior to photosystem I. The 33 kDa extrinsic protein (MSP) of oxygen evolving
      complex, the LHCII apoprotein and the beta-subunit of ATPsynthase showed the
      declined levels with the progress of cotyledon age. However, the extents of loss
      of these proteins were not as high as the reaction centre proteins of photosystem
      II and the Cyt f. These results provide that during senescence, proteins of
      thylakoid membranes degrade in a specific temporal sequence and thereby affect
      the temporal photochemical functions in Cucumis sativus cotyledons.

PMID- 11531095
TI  - New bioactive chalcones in propolis from El Salvador.
AB  - 2',3'-Dihydroxy-4,4'-dimethoxychalcone (1) and 2',3',4-trihydroxy-4'-methoxy
      chalcone, two new chalcones, were isolated from propolis from El Salvador. The
      compounds showed significant antibacterial and antifungal activity and moderate
      toxicity to Artemia salina nauplii.

PMID- 11531096
TI  - Chemical composition and behavioral responses of the marine insect Halobates
      hawaiiensis (Heteroptera: Gerridae).
AB  - Halobates is the only insect genus with representatives in the open ocean. How
      adults find one another at sea has long been an intriguing issue. Since chemical
      communications have been demonstrated in a related marine veliid Trochopus, and
      laboratory bioassays indicated behavioral differences between males and females
      when insect extracts were presented, we carried out similar studies on Halobates.
      Analyses of surface lipid constituents of female and male Halobates hawaiiensis
      revealed marked differences. Palmitic and oleic acid, major constituents in the
      male extracts, were absent in the female extract, whereas nonacosenol, dominating
      the female extracts, was not detected in the male extracts. Analyses of nymphal
      extracts indicated an intermediate chemical profile. Surface waxes of all insect
      stages investigated showed nonacosanol and isononacosanol to be main components.
      "Headspace" analyses of airborne chemicals showed high levels of 4-hydroxy-4
      methyl-2-pentanone and benzaldehyde from the male, whereas benzyl alcohol was the
      main component in the female mixture.

PMID- 11531097
TI  - Insect growth regulator and insecticidal activity of beta-dihydroagarofurans from
      Maytenus spp. (Celastraceae).
AB  - From the aerial parts of Maytenus disticha, we have isolated 9beta-benzoyloxy
      1alpha,2alpha,6beta,8alpha,15penta-acetoxy-dihydro-beta-agarofuran (1) and from
      seeds of Maytenus boaria 9beta-furoyloxy-1alpha,6beta,8alpha-triacetoxy-dihydro
      beta-agarofuran (2). These compounds and their MeOH and hexane/ethyl acetate (1:1
      v/v) extracts were evaluated for their effects on the fall armyworm (Spodoptera
      frugiperda). Toosendanin, a commercial insecticide derived from Melia azedarach
      was used as a positive control. When tested for activity using neonate larvae in
      a nochoice artificial diet bioassays, the agarofurans 1, 2 and toosendanin as
      well as the MeOH and hexane/EtOAc extracts caused significant growth inhibitory
      effects with GC50 of 7.55; 3.84; 1.75; 14.0 and 7.3 ppm at 7 days, respectively.
      Compounds 1 and 2 caused 100% larval mortality at 25 and 15 ppm, respectively.
      MeOH and hexane/EtOAc extracts caused 100% larval mortality at 25.0 ppm,
      respectively, they also increased the development time of surviving larvae and a
      significant delay for the time of pupation and adult emergence. These compounds
      showed comparable potency of activity with toosendanin. Acute toxicity against
      adults of S. frugiperda was also found, for hexane/EtOAc extract and 2 had the
      most potent activity with LD50 value of 4.7 and 1.9 ppm, respectively. MeOH
      extract, hexane/EtOAc extract, 1 and 2 caused acetylcholinesterase inhibition
      with 78.0, 89.2, 79.3 and 100% inhibition at 15.0 ppm, respectively. Therefore,
      the furoyloxy agarofuran may be responsible for the insecticidal activity of
      these plants.

PMID- 11531098
TI  - Dibucaine-induced modification of sodium transport in toad skin and of model
      membrane structures.
AB  - The interaction of the local anesthetic dibucaine with the isolated toad skin and
      membrane models is described. The latter consisted of human erythrocytes,
      isolated unsealed human erythrocyte membranes (IUM), large unilamellar vesicles
      (LUV) of dimyristoylphosphatidylcholine (DMPC) and phospholipid multilayers built
      up of DMPC and dimyristoylphosphatidylethanolamine (DMPE), representative of
      phospholipid classes located in the outer and inner monolayers of the human
      erythrocyte membrane, respectively. Results indicate a significant decrease in
      the potential difference (PD) and in the short-circuit current (Isc) after the
      application of dibucaine in toad skin, which may be interpreted as reflecting
      inhibition of the active transport of ions. This finding might be explained on
      the basis of the results obtained from fluorescence spectroscopy and X-ray
      diffraction studies on membrane models. In fact, dibucaine induced structural
      perturbations in IUM, DMPC LUV and phospholipid multilayers. Scanning electron
      microscopy revealed that dibucaine induced erythrocyte stomatocytosis. According
      to the bilayer couple hypothesis an echinocytic type of shape change would have
      been expected given the preferential interaction of dibucaine with DMPC. Although
      it is still premature to define the molecular mechanism of action of dibucaine,
      the experimental results confirm the important role played by the phospholipid
      bilayers in the association of the anesthetic with cell membranes.

PMID- 11531099
TI  - Influence of dodecyltrimethylammonium halides on interaction of phenyltin
      compounds with model membranes.
AB  - The effects were studied of dodecyltrimethylammonium chloride (DTAC),
      dodecyltrimethylammonium bromide (DTAB) and dodecyltrimethylammonium iodide
      (DTAI) on thermotropic phase behaviour of phosphatidylcholine bilayers, as well
      as on 1H NMR and 31P NMR spectra, in the presence of diphenyltin dichloride
      (DPhT) and triphenyltin chloride (TPhT). The obtained results indicate that in
      the presence of the surfactant studied the interaction of phenyltin compounds
      with model membranes was changed and the changes depended on the kind of the
      counterion. The surfactants studied (especially DTAC) decrease the ability of
      phenyltin compounds to induce structural changes in the bilayer. It is suggested
      that DTAB, and especially DTAC, prevent DPhT induced interdigitated phase
      formation as well as formation of an inverted hexagonal phase (H(II)) in the case
      of TPhT/DPPC liposomes.

PMID- 11531100
TI  - On the mode of action of methionine enkephalin, FK 33-824 and naloxone in
      regulating the hemolymph glucose level in the fresh water field crab Oziotelphusa
      senex senex.
AB  - The possible involvement of opioid system in the regulation of hemolymph glucose
      level in the fresh water crab Oziotelphusa senex senex Fabricius, was
      investigated. Opioid agonist and antagonist was also used in addition to
      methionine-enkephalin itself. Injection of the opioid, methionine-enkephalin and
      FK 33-824 significantly elevated hemolymph glucose level. In contrast, injection
      of naloxone in to crab resulted in decrease in hemolymph glucose level. Injection
      of naloxone prior to injection of methionine-enkephalin blocked the hyperglycemic
      action of methionine-enkephalin. Injection of methionine-enkephalin, FK 33824 and
      naloxone produced no significant effect on hemolymph glucose level in eyestalk
      less crab. The alterations in the intact crab hemolymph glucose level
      hypothesised to be due to stimulation of release of hyperglycemic hormone during
      methionine-enkephalin and FK 33824 treatment and blocking of release of
      hyperglycemic hormone during naloxone treatment from the eyestalks of crab
      Oziotelphusa senex senex.

PMID- 11531101
TI  - Biological durability and oxidative potential of man-made vitreous fibres as
      compared to crocidolite asbestos fibres.
AB  - In this study we investigated relationships between redox properties and
      biodurability of crocidolite asbestos fibres and three different man-made
      vitreous fibres (MMVF): traditional stone wool fibres (MMVF 21), glass fibres
      (MMVF 11) and refractory ceramic fibres (RCF). Each fibre type was incubated up
      to 22 weeks in four different incubation media: gamble solution (GS) pH 5.0 and
      pH 7.4, representing blood plasma without proteins, and surfactant-like solution
      (SLS) pH 5.0 and pH 7.4. During incubation time aliquots of incubation mixtures
      were removed and analysed in a biochemical model reaction, mimicking activated
      phagocytes. In addition, changes of fibre morphology and chemical composition
      were examined using SEM- and EDX-technology. In the presence of crocidolite
      asbestos fibres and MMVF 21 the formation of OH*-radicals according to the Haber
      Weiss sequence could be demonstrated, whereas MMVF 11 and RCF showed no
      reactivity. Crocidolite asbestos fibres exhibited a significant higher activity
      compared with the stone wool fibres at the onset of incubation. The oxidative
      capacities of these fibre types were shown to depend on both specific surface
      area and iron content. The oxidative potentials of crocidolite asbestos fibres as
      well as MMVF 21 were not constant during incubation over several weeks in each
      incubation medium. The reactivities showed sinoidal curves including reactivities
      much higher than those at the onset of incubation time. These irregular changes
      of oxidative capacity may be explained by changes of the redox state of fibre
      surface-complexed iron. Furthermore our results showed clear differences between
      incubation of fibres in GS and SLS, respectively, indicating that phospholipids
      play an important part in fibre dissolution behaviour and oxidative reactivity.
      In conclusion we suggest, that biodurability testing procedures should not
      exclusively concentrate on dissolution rates of fibres. They should include fibre
      characteristics concerning known pathogenic mechanisms to evaluate the real toxic
      potential of the fibre type looking at. Secondly we suggest, that phospholipids
      should be constituents of incubation liquids used for standardised fibre
      biodurability test procedures thus representing more realistic incubation
      conditions.

PMID- 11531102
TI  - Mechanism of carbon tetrachloride-induced hepatotoxicity. Hepatocellular damage
      by reactive carbon tetrachloride metabolites.
AB  - CCl4-induced liver damage was modeled in monolayer cultures of rat primary
      hepatocytes with a focus on involvement of covalent binding of CCl4 metabolites
      to cell components and/or peroxidative damage as the cause of injury. (1)
      Covalent binding of 14C-labeled metabolites was detected in hepatocytes
      immediately after exposure to CCl4. (2) Low oxygen partial pressure increased the
      reductive metabolism of CCl4 and thus covalent binding. (3) [14C]-CCl4 was bound
      to lipids and to proteins throughout subcellular fractions. Binding occurred
      preferentially to triacylglycerols and phospholipids, with phosphatidylcholine
      containing the highest amount of label. (4) The lipid peroxidation potency of
      CCl4 revealed subtle differences compared to other peroxidative substances, viz.,
      ADP-Fe3+ and cumol hydroperoxide, respectively. (5) CCl4, but not the other
      peroxidative substances, decreased the rate of triacylglycerol secretion as very
      low density lipoproteins. (6) The anti-oxidant vitamin E (alpha-tocopherol)
      blocked lipid peroxidation, but not covalent binding, and secretion of
      lipoproteins remained inhibited. (7) The radical scavenger piperonyl butoxide
      prevented CCl4-induced lipid peroxidation as well as covalent binding of CCl4
      metabolites to cell components, and also restored lipoprotein metabolism. The
      results confirm that covalent binding of the CCl3* radical to cell components
      initiates the inhibition of lipoprotein secretion and thus steatosis, whereas
      reaction with oxygen, to form CCl3-OO*, initiates lipid peroxidation. The two
      processes are independent of each other, and the extent to which either process
      occurs depends on partial oxygen pressure. The former process may result in
      adduct formation and, ultimately, cancer initiation, whereas the latter results
      in loss of calcium homeostasis and, ultimately, apoptosis and cell death.

PMID- 11531103
TI  - Evaluation of delayed apoptotic response in lethally irradiated human melanoma
      cell lines.
AB  - To assess the lethal doses of gamma radiation and corresponding apoptotic
      response in new established human melanoma cell lines we exposed exponentially
      growing cultures to 8-100 Gy gamma radiation. The apoptosis and cell survival
      were determined by trypan blue exclusion, terminal deoxynucleotidyl transferase
      mediated dUTP nick end labeling (TUNEL) reaction, agarose gel electrophoresis,
      colony forming assay, and long-term survival assay. The maximal DNA fragmentation
      3 days after irradiation was observed in cultures irradiated with 20 Gy (36.9%
      TUNEL positive cells). The cultures irradiated with 50 and 100 Gy contained 18.7%
      and 16.4% TUNEL positive cells, respectively. Cultures exposed to 8 and 20 Gy
      gamma radiation recovered by week 3-4. Lethally irradiated (50 and 100 Gy)
      cultures which contained less apoptotic cells by day 3 died by week 5. A
      detectable increase in melanoma cell pigmentation after irradiation was also
      observed. The survival of human melanoma cell cultures after exposure to gamma
      radiation does not correlate with the level of apoptotic cells by day 3. At high
      radiation doses (> 50 Gy) when the radiation induced cell pigmentation is not
      inhibited the processes of apoptotic DNA fragmentation might be preferentially
      inactivated.

PMID- 11531104
TI  - Determination of chemical composition of Turkish propolis.
AB  - The aim of the present work is to study the chemical composition of Turkish
      propolis. Propolis samples were collected from different regions of Turkey
      (Bursa, Erzurum-Askale, Gumushane-Sogutagil and Trabzon-Caglayan) in 1999.
      Ethanol extracts of propolis (EEP) were prepared for chemical analysis, using gas
      chromatograph coupled with mass spectrometry (GC-MS). Our findings show that
      propolis samples from Trabzon and Gumushane region have a similar chemical
      composition. In both samples aromatic acids, aliphatic acids and their esters,
      and also ketone derivatives are the main compound groups. The chemical
      composition of the single sample that was collected from Erzurum region shows a
      very different pattern than the other two samples. In this propolis, the main
      compounds are aromatic acid esters and alcohols. However, it contains a high
      amount of amino acids compared to the other samples. The other samples collected
      from three different region of Bursa City are rich with flavavones, aromatic
      acids and their esters, terpenoids, flavones and ketones.

PMID- 11531105
TI  - Bioorganic applications of semisynthetic DNA-protein conjugates.
AB  - Semisynthetic DNA-protein conjugates are versatile molecular tools useful, for
      instance, in the self-assembly of high-affinity reagents for immunological
      detection assays, the fabrication of highly functionalized laterally
      microstructured biochips, and the biomimetic "bottom-up" synthesis of
      nanostructured supramolecular devices. This concept paper summarizes the current
      state-of-the-art concerning the synthesis, characterization, and applications of
      such hybrid molecules, and also draws perspectives on future developments.

PMID- 11531106
TI  - Self-assembled organometallic [12]metallacrown-3 complexes.
AB  - The reaction of [(arene)RuCl2]2 (arene = C6H6, cymene, C6H3Et3, or C6Me6) or
      [Cp*RhCl2]2 with 3-hydroxy-2-pyridone in the presence of Cs2CO3 gives trinuclear
      metallamacrocyclic complexes. The self-assembly process was shown to be
      completely diastereoselective, and a racemic mixture of complexes with
      M(R)M(R)M(R) or MsMsMs (M=Ru, Rh) configuration was obtained. Plausible
      mononuclear intermediates of the formula [(arene)RuCl(C5H4NO2)] (arene = cymene,
      C6Me6) have been isolated and characterized. A structurally related trimer was
      synthesized by using [(cymene)RuCl2]2 and 3-acetamido-2-pyridone instead of 3
      hydroxy-2-pyridone. The macrocycles were shown to be highly potent ionophores for
      Na+ and/or Li+ with negligible affinities for the larger cation K+. The
      selectivities of the receptors depend on the pi-ligand present: whereas the
      (C6H6)Ru- and (cymene)Ru complexes bind both Li+ and Na+, the (C6Me6)Ru-,
      (C6H3Et3)Ru-, and Cp*Rh complexes bind exclusively Li+. For all receptors, the
      presence of alkali metal ions can be detected electrochemically: the peak
      potential is shifted by > 300 mV toward anionic potential upon binding. This
      behavior was utilized to detect Li+ and Na+ colorimetrically. Single crystal X
      ray analyses have been carried out on eight complexes, four of which are bound to
      an alkali metal halide ion pair. Structural parameters, which affect the affinity
      and selectivity are discussed. A computational study on [[MX][12]crown-3]
      complexes (M =Li, Na; X=Cl, Br, I) was performed in order to compare relevant
      bond lengths and angles of the energy-minimized structures with those of the
      organometallic receptors.

PMID- 11531107
TI  - Ba4Si3Br2: a double salt of barium bromide and barium silicide containing a novel
      cyclotrisilicide unit.
AB  - A new compound of the composition Ba4Si3Br2 was obtained by reacting BaSi with a
      melt of BaBr2. Ba4Si3Br2 may be described as a double salt between a Zintl phase
      and a halide. The structure was determined by single-crystal X-ray diffraction
      (P21c, a= 1504.1(2), b = 884.5(1), c = 880.2(1) pm, beta = 101.93(2) degrees, R =
      0.041 Rw = 0.079). The crystal structure contains isolated barium cations and
      bromide anions as well as novel singly bonded cyclotrisilicid units. The
      electronic structure has been studied by linear Muffin tin orbital (LMTO) band
      structure calculations, which reveal semiconducting behavior with a band gap of
      about 0.1 eV, and by an analysis of the electron localization function.

PMID- 11531109
TI  - Efficient preparation of monoadducts of [60] fullerene and anthracenes by
      solution chemistry and their thermolytic decomposition in the solid state.
AB  - The efficient preparation of monoadducts of [60]fullerene and seven anthracenes
      (anthracene, 1-methylanthracene, 2-methylanthracene, 9-methylanthracene, 9,10
      dimethylanthracene, 2,3,6,7-tetramethylanthracene, and 2,6-di-tert
      butylanthracene) by cycloaddition in solution is described. The seven mono
      adducts of [60]fullerene and the anthracenes were characterized spectroscopically
      and were obtained in good yields as crystalline solids. The monoadducts of
      [60]fullerene and anthracene, 1-methylanthracene, 2-methylanthracene and 9,10
      dimethylanthracene crystallized directly from the reaction mixture. The
      thermolytic decomposition at 180 degrees C of the crystalline monoadducts of
      [60]fullerene and anthracene, 1-methylanthracene, 9-methylanthracene and 9,10
      dimethylanthracene all gave rise to the specific formation of a roughly 1:1
      mixture of [60]fullerene and the corresponding antipodal bisadducts ("trans-1"
      bisadducts) of [60]fullerene and the anthracenes. In contrast, the crystalline
      monoadducts of [60]fullerene and the anthracene derivatives 2-methylanthracene,
      2,3,6,7-tetramethylanthracene and 2,6-di-tert-butylanthracene all decomposed to
      [60]fullerene and anthracenes (without detectable formation of bisadducts) upon
      heating in the solid state to temperatures of 180 to 240 degrees C. The formation
      of the antipodal bisadducts from thermolytic decomposition of crystalline samples
      of the monoadducts was rationalized by topochemical control.

PMID- 11531108
TI  - On the formation of radical dications of protonated amino acids in a
      "microsolution" of water or acetonitrile and their reactivity towards the
      solvent.
AB  - In high-energy collisions (50 keV) between O2 and protonated amino acids AH+,
      radical dications AH2+* are formed for A = Phe, His, Met, Tyr, and Trp. When
      solvated by water or acetonitrile (S), AH2+*(S)1,2 are formed for A = Arg, His,
      Met, Tyr, and Trp. The stability of the hydrogen-deficient AH2+* in the
      "microsolution" depends on the energetics of the electron transfer reaction AH2+*
      +S --> AH++S+*, the hydrogen abstraction reaction AH2+*+S --> AH2(2+)+[S-H]*, and
      the proton transfer reaction AH2+* + S --> A+*+SH+. Using B3LYP/ 6
      311+G(2d,p)//B3LYP/6-31+G(d) model chemistry, we describe these three reactions
      in detail for A=Tyr and find that the first two reactions are unfavorable whereas
      the third one is favorable. However, energy is required for the formation of
      Tyr+* and SH+ from TyrH2+*(S) to overcome the Coulomb barrier, which renders the
      complex observable with a life-time larger than 5 micros. The ionization energy,
      IE, of TyrH+ is calculated to be 11.1 eV in agreement with an experimental
      measurement of 10.1+/-2.1 eV ([IE(CH3CN)+IE(Tyr)]/ 2); hydration further lowers
      the IE by 0.3 eV [IE(TyrH+(H2O) = 10.8 eV, calculated]. We estimate the
      ionization energies of TrpH+, HisH+, and MetH+ to be 10.1+/-2.1 eV, 12.4+/-0.2
      eV, and 12.4+/-0.2 eV, and that of PheH+ to be larger than 12.6 eV.

PMID- 11531110
TI  - Comparative investigation of ruthenium-based metathesis catalysts bearing N
      heterocyclic carbene (NHC) ligands.
AB  - Exchange of one PCy3 unit of the classical Grubbs catalyst 1 by N-heterocyclic
      carbene (NHC) ligands leads to "second-generation" metathesis catalysts of
      superior reactivity and increased stability. Several complexes of this type have
      been prepared and fully characterized, six of them by X-ray crystallography.
      These include the unique chelate complexes 13 and 14 in which the NHC- and the Ru
      CR entities are tethered to form a metallacycle. A particularly favorable design
      feature is that the reactivity of such catalysts can be easily adjusted by
      changing the electronic and steric properties of the NHC ligands. The catalytic
      activity also strongly depends on the solvent used; NMR investigations provide a
      tentative explanation of this effect. Applications of the "second-generation"
      catalysts to ring closing alkene metathesis and intramolecular enyne
      cycloisomerization reactions provide insights into their catalytic performance.
      From these comparative studies it is deduced that no single catalyst is optimal
      for different types of applications. The search for the most reactive catalyst
      for a specific transformation is facilitated by IR thermography allowing a rapid
      and semi-quantitative ranking among a given set of catalysts.

PMID- 11531111
TI  - Constructing conformationally constrained macrobicyclic musks.
AB  - To investigate the structure-odor correlation of musks, (12R)-12-methyl-13
      tridecanolide (1), a macrocyclic musk, and 13-tridecanolide, its non-musky
      demethyl analogue, were conformationally constrained by introduction of methylene
      bridges between C-3 and C-8 or C-9. These [7.5.1]- and [8.4.1]-macrobicycles were
      synthesized starting from bicyclo[5.3.1]undec-8-en-9-one (3) and
      bicyclo[4.3.1]dec-7-en-8-one (8), respectively, by a sequence consisting of
      catalytic hydrogenation, alpha-alkylation with a TBS-protected (tert
      butyldimethylsilyl) hydroxy halide, acid-catalyzed cyclization, oxidative
      cleavage of the formed enol ether double bond, and subsequent reduction of the
      carbonyl group via its tosylhydrazone. The compound (1R,6R,9R)-(+)-6-methyl-4-oxa
      bicyclo[7.5.1]pentadecan-3-one (22) was found to possess the most pronounced musk
      odor, and this was rationalized by a superposition analysis with the polycyclic
      aromatic musk odorant (4S,7R)-Galaxolide (2). In its (1S,6R,9S)-(+)-stereoisomer
      23 as well as in (1S,6R, 10R)-(+)-6-methyl-4-oxabicyclo[8.4.1]-pentadecan-3-one
      (18) the (6R)-methyl group seems to hinder the interaction with the musk
      receptor, while the demethyl compounds 7 and 12 showed only very faint odors.

PMID- 11531112
TI  - Highly functionalized dimeric tetraethynylethenes and expanded radialenes: strong
      evidence for macrocyclic cross-conjugation.
AB  - A selection of dimeric tetraethynylethenes (TEEs) and perethynylated expanded
      radialenes, containing different donor/acceptor substitution patterns, have been
      prepared and fully characterized. The first X-ray crystal structure of an
      expanded [6]radialene, with twelve peripheral 3,5-di(tert-butyl)phenyl
      substituents, is presented. This macrocycle, the all-carbon core of which is
      isomeric with fullerene C60, adopts a non-planar, "chair-like" conformation. Also
      a TEE dimer, carrying N,N-dimethylaniline donor substituents, has been subjected
      to an X-ray crystallographic analysis. The electronic properties were studied by
      UV/Vis spectroscopy and electrochemistry, providing fundamental insight into
      mechanisms of pi-electron delocalization in the acyclic and macrocyclic
      chromophores. Donor or donor-acceptor-substituted dimeric TEE derivatives show
      very strong absorptions extending over the entire UV/Vis region; their longest
      wavelength absorption bands have high charge-transfer character. Macrocyclic
      cross-conjugation in the expanded radialenes becomes increasingly efficient with
      increasing donor-acceptor polarization. A dual, strongly solvent-polarity
      dependent fluorescence was observed for a tetrakis(N,N-dimethylaniline)
      substituted dimeric TEE; this interesting emission behavior is explained by the
      twisted intramolecular charge-transfer (TICT) state model. Donor-substituted
      expanded radialenes display huge resonance-enhanced third-order nonlinear optical
      coefficients.

PMID- 11531113
TI  - Does the interconversion of polysulfur compounds proceed via hypervalent
      intermediates? An ab initio MO study.
AB  - Ab initio MO calculations at the CCSD(T)/6-311++G(2df,p)//MP2/6-311++G** level
      have been carried out to determine the reaction energies and Gibbs energies of
      the homolytic dissociation of the S-S bonds in the chainlike sulfanes H2Sn (n = 2
      4). Good agreement with the experimental data is observed. At the same level of
      theory, the formation of the hypothetical sulfuranes H2S(SH)2, H2S(SSH)2, and
      S(SH)4 from H2S and the mentioned sulfanes has been studied. Species of this type
      had been proposed as intermediates in the interconversion reactions of polysulfur
      compounds (e.g., formation of S7 from S8 and vice versa). The three sulfuranes
      serve here as model compounds. On the basis of the Gibbs energies and activation
      energies at 298 K, it is shown that the formation of the three sulfuranes from
      sulfanes requires too much energy and activation energy to successfully compete
      with homolytic dissociation reactions. In addition, the formation of the
      methylsubstituted sulfurane S(SMe)4 from the sulfanes Me2S2 and Me2S3 was studied
      to elucidate the mechanism of the formal exchange of sulfur atoms between
      polysulfane molecules. However, both the reaction energy of 199 kJ mol(-1) and
      the activation energy of 287 kJ mol(-1), calculated at the MP2/6-31G* level, are
      much higher than the homolytic dissociation energy of the S-S bonds in chain- and
      ringlike polysulfur compounds, such as Me2S4 (140 kJ mol(-1)) and sulfur
      homocycles (150 kJ mol(-1)). Therefore, it is concluded that the observed
      interconversion reactions of sulfur rings and of chainlike polysulfanes do not
      proceed via sulfurane-type intermediates. Instead, these reactions will take
      place by a radical chain mechanism at high temperatures, while at temperatures
      below 100 degrees C they are most probably initiated either by traces of
      nucleophiles that are present as impurities or by the polar surface groups
      usually present on the walls of the vessels used.

PMID- 11531114
TI  - Iron porphyrins as models of cytochrome c oxidase.
AB  - A series of iron porphyrins has been synthesized as models of cytochrome c
      oxidase; their activity as 4e catalysts in the reduction of dioxygen has been
      studied at pH 7. These compounds have been obtained by grafting very different
      residues onto the same iron complex, namely tripodal tetraamines, pickets, and
      straps, in order to change the environment of the metal center. In the case of
      porphyrins bearing a tripodal cap, the secondary amines have been alkylated with
      different substituents so as to modify the electronic environment of the distal
      pocket. Surprisingly, when the iron porphyrin is functionalized with four
      identical acrylamido pickets, the resulting complex exhibits biomimetic activity
      in that it catalyzes oxygen reduction with almost no production of hydrogen
      peroxide. The crystal structure of the redox-inactive zinc(II) analogue is
      reported; this shows how the metal influences the spatial arrangement of the four
      pickets through axial coordination and hydrogen bonding. Even a bis-strapped iron
      porphyrin, for which no dimerization or self-aggregation can occur at the
      electrode surface, acts as a 4e catalyst for O2 reduction. It is thus
      demonstrated that at pH close to physiological values, the iron porphyrin is an
      intrinsically efficient catalyst for the reduction of oxygen to water.

PMID- 11531115
TI  - Dependence of enantioselectivity on the distribution of a chiral hydrogenation
      catalyst between an aqueous and a micellar phase: investigations using pulsed
      field gradient spin echo NMR spectroscopy.
AB  - The enantioselectivity obtained from rhodium complex catalyzed hydrogenations
      conducted in water can often be increased considerably by the addition of
      amphiphiles. At present the reasons for this increase in selectivity are not
      fully understood. The application of pulsed field gradient spin echo NMR (PGSE
      NMR) spectroscopy to determine the average diffusion coefficients of the
      catalysts in both known and novel examples of asymmetric hydrogenation shows
      definitively that the increase in enantioselectivity is coupled with an
      aggregation of the catalyst to the micelles. This aggregation or solubilization
      of the catalyst in the micelles leads to the formation of a new colloidal phase
      in the aqueous solution. This phase has stronger hydrophobic properties, and thus
      the hydrogenation is more comparable to those conducted in a hydrophobic or less
      polar organic solvent. In the case of anionic amphiphiles, which form amphiphilic
      salts with the cationic catalyst, the embedment of the catalyst complex into the
      micelle is generally complete. The whole hydrogenation then takes place
      exclusively inside the micelles, leading to high enantioselectivity. If the
      catalyst is not completely embedded into the micelle, for example in the cases of
      nonionic or cationic surfactant solutions, the solubility of the substrate plays
      an important role. For soluble substrates the hydrogenation of the substrate
      occurs predominately in the aqueous phase itself, leading to very poor
      enantioselectivities. In these cases, only the use of a large excess of
      amphiphile, far above the critical micelle concentration (cmc), will lead to
      higher enantioselectivities due to a shift of the equilibrium towards the
      micellar bonded forms of catalyst and substrate. In contrast, poorly soluble
      substrates exhibit a high tendency to be incorporated into micelles, which leads
      to much higher enantioselectivities if the cmc of the surfactant is small enough.
      Changes in the cmc of amphiphiles caused by their aggregation with catalysts
      could also be estimated. The variation in selectivity observed for the catalysts
      containing seven-membered, flexible chelate rings is apparently due to changes in
      their conformation in the less polar micellar medium, and this effect is also
      seen in organic solvents. As expected, catalysts containing smaller chelate rings
      show this effect to a considerably lower extent since they are conformationally
      more rigid.

PMID- 11531116
TI  - Direct monitoring kinetic studies of DNA polymerase reactions on a DNA
      immobilized quartz-crystal microbalance.
AB  - Catalytic reactions of DNA polymerase I from E. coli (Klenow fragment, KF) were
      monitored directly with a template/primer (40/25- or 75/25-mer)-immobilized 27
      MHz quartz-crystal microbalance (QCM). The 27-MHz QCM is a very sensitive mass
      measuring device in aqueous solution, as the frequency decreases linearly with
      increasing mass on the QCM electrode at the nanogram level. Three steps in
      polymerase reactions which include 1) binding of DNA polymerase to the primer on
      the QCM (mass increase); 2) elongation of complementary nucleotides along the
      template (mass increase); and 3) release of the enzyme from the completely
      polymerized DNA (mass decrease), could be monitored continuously from the time
      dependencies of QCM frequency changes. The binding constant (Ka) of KF to the
      template/primer DNA was 10(8)M(-1) (k(on) = 10(5)M(-1)s(-1) and k(off)= 10(-3)s(
      1)), and decreased to 10(6)M(-1) (k'on = 10(4)M(-1)s(-1) and k'off = 10(-2)s(-1))
      for completely polymerized DNA. This is due to the 10-fold decrease in binding
      rate constant (k(on)) and 10-fold increase in dissociation rate constant (k(off))
      for completed DNA strands. Ka values depended slightly on the template and primer
      sequences. The kinetic parameters in the elongation process (k(cat) and Km)
      depended only slightly on the DNA sequences. The repair process during the
      elongation catalyzed by KF could also be monitored in real time as QCM frequency
      changes.

PMID- 11531117
TI  - Inhibition of peroxynitrite-induced nitration of tyrosine by glutathione in the
      presence of carbon dioxide through both radical repair and peroxynitrate
      formation.
AB  - Peroxynitrite (ONOO-/ONOOH) is assumed to react preferentially with carbon
      dioxide in vivo to produce nitrogen dioxide (NO2*) and trioxocarbonate(1-) (CO3*
      ) radicals. We have studied the mechanism by which glutathione (GSH) inhibits the
      NO2*/CO3*--mediated formation of 3-nitrotyrosine. We found that even low
      concentrations of GSH strongly inhibit peroxynitrite-dependent tyrosine
      consumption (IC50 = 660 microM) as well as 3-nitrotyrosine formation (IC50) = 265
      microM). From the determination of the level of oxygen produced or consumed under
      various initial conditions, it is inferred that GSH inhibits peroxynitrite
      induced tyrosine consumption by re-reducing (repairing) the intermediate tyrosyl
      radicals. An additional protective pathway is mediated by the glutathiyl radical
      (GS*) through reduction of dioxygen to superoxide (O2*-) and reaction with NO2*
      to form peroxynitrate (O2NOOH/O2NOO-), which is largely unreactive towards
      tyrosine. Thus, GSH is highly effective in protecting tyrosine against an attack
      by peroxynitrite in the presence of CO2. Consequently, formation of 3
      nitrotyrosine by freely diffusing NO2* radicals is highly unlikely at
      physiological levels of GSH.

PMID- 11531118
TI  - Highly efficient deacetylation by use of the neutral organotin catalyst
      [tBu2SnOH(Cl)]2.
AB  - Deprotection of acetyl esters is effected cleanly by the neutral organotin
      catalyst, [tBu2SnOH(Cl)]2. The mildness of the reaction gives rise to great
      synthetic versatility and in the process a variety of functional groups are
      tolerated. Differentiations between primary, secondary, and tertiary alcohols and
      between acetyl ester and other esters are feasible. No racemization occurs with
      chiral acetyl esters. Exclusive deprotection of primary acetyl esters in
      carbohydrates and nucleosides is observed. The crude product thus obtained can be
      used for further reactions without purification.

PMID- 11531119
TI  - Bis(amino acid) oxalyl amides as ambidextrous gelators of water and organic
      solvents: supramolecular gels with temperature dependent assembly/dissolution
      equilibrium.
AB  - Bis(LeuOH) (1a), bis-(ValOH) (2a) and bis(PhgOH) (5a) (Phg denotes (R)
      phenylglycine) oxalyl amides are efficient low molecular weight organic gelators
      of various organic solvents and their mixtures as well as water, water/DMSO, and
      water/DMF mixtures. The organisational motifs in aqueous gels are dominated
      primarily by lipophilic interactions while those in organic solvents are formed
      by intermolecular hydrogen bonding. Most of the gels are thermoreversible and
      stable for many months. However, 2a forms unstable gels with organic solvents
      which upon ageing transform into variety of crystalline shapes. For some
      1a/alcohol gels, a linear correlation between alcohol dielectric constants
      (epsilon) and gel melting temperatures (Tg) was found. The 1H NMR and FTIR
      spectroscopic investigations of selected gels reveal the existence of temperature
      dependent network assembly/dissolution equilibrium. In the 1H NMR spectra of gels
      only the molecules dissolved in entrapped solvent could be observed. By using an
      internal standard, the concentration of dissolved gelator molecules could be
      determined. In FTIR spectra, the bands corresponding to network assembled and
      dissolved gelator molecules are simultaneously present. This enabled
      determination of the Kgel values by using both methods. From the plots of InKgel
      versus 1/T, the deltaHgel values of selected gels have been determined (
      deltaHgel in 10-36 kJ mol(-1) range) and found to be strongly solvent dependent.
      The deltaHgel values determined by 1H NMR and FTIR spectroscopy are in excellent
      agreement. Crystal structures of 2a and rac-5a show the presence of
      organisational motifs and intermolecular interactions in agreement with those in
      gel fibres elucidated by spectroscopic methods.

PMID- 11531120
TI  - Diketopiperazine receptors: a novel class of highly selective receptors for
      binding small peptides.
AB  - A novel class of receptors consisting of a rigid diketopiperazine backbone and
      peptidic side chains has been developed with the use of combinatorial chemistry.
      These diketopiperazine receptors interact with peptidic substrates with high
      specificity as shown in combinatorial on-bead assays. The central
      diketopiperazine moiety can be easily obtained from natural 4-hydroxyproline and
      serves as a rigidifying template for the peptidic modules which allow for
      structural as well as functional variations. Screenings of several dye-marked
      receptor prototypes against an encoded tripeptide library demonstrated not only
      the high binding specificities of the diketopiperazine receptors towards peptides
      but also revealed that small structural changes induce significant changes in
      their binding properties.

PMID- 11531121
TI  - [Ga18(SitBu3)8] and [Ga22(SitBu3)8]--syntheses and structural characterization of
      novel gallium cluster compounds.
AB  - The novel neutral gallium cluster compounds [Ga18R*8] (1) and [Ga22R*8] (2) are
      obtained by warming up a metastable solution of gallium(I) bromide in THF/C6H5CH3
      after addition of equimolar amounts of supersilyl sodium NaR* from -78 degrees C
      to room temperature (R* = SitBu3 = supersilyl). From X-ray structure analyses,
      the observed arrangements of the 18 and 22 Ga atoms in 1 and 2, respectively, are
      comparable with an 18 atom section of the beta-Ga modification, or show at least
      some kind of relationship to a 22 atom section of the Ga-III modification. This
      allows a description of both the clusters as metalloid. The topology of the atoms
      in 2 is also well explained by the Wade-Mingos rules as an eightfold capped closo
      Ga14 cluster, whereby the Ga atoms of Ga14 occupy the center and the corners of a
      cuboctahedron with one Ga3 face replaced by a Ga4 face. Some concepts are
      presented about the formation mechanism, the cluster growth, and the metalloid
      character of the two Ga cluster compounds.

PMID- 11531122
TI  - Calixarene--poly(dithiophene)-based chemically modified electrodes.
AB  - The stepwise synthesis of cone and partial cone 1,3-bridged n-propoxy
      calix[4]crown ethers ("monomers" 2 and 3) with an electropolymerizable 2,2'
      dithiophene-3-yl-hexylene functionality at the lower rim, is described. The
      potential of 2 and 3 as sensing agents for alkali metal ions was investigated by
      1H NMR titration experiments with NaSCN and KSCN. The results obtained have
      confirmed that the presence of the heterocyclic subunit does not affect the well
      known size-selectivity observed with calix[4]crowns. Monomers 2 and 3 were
      electropolymerized (Pt as a working electrode, CH2Cl2/CH3CN, Bu4NPF6) to produce
      the title chemically modified electrodes (CMEs). After coating with a PVC
      membrane containing a lipophylic cation exchanger, CMEs based on calix[4]-crown-5
      2b (cone) and 3b (partial cone) were tested for the potentiometric recognition of
      alkali metal ions in aqueous solution. In agreement with NMR titration studies, a
      satisfactory potentiometric response in terms of K+/Na+ selectivity was obtained
      only with CME 2b (pK(K/Na) 1.51). The amperometric responses of PVC-uncoated CMEs
      were studied by cyclic voltammetry (CV) experiments in CH3CN solution. High Na-
      selectivity was found with the CME based on partial cone calix[4]crown-4 3a, and
      frequency response analysis (FRA) measurements support this finding.

PMID- 11531123
TI  - Enantiospecific synthesis of the (9S,18R)-diastereomer of the leukocyte adhesion
      inhibitor cyclamenol A.
AB  - Cyclamenol A is one of the very few non-carbohydrate and non-peptide natural
      products that inhibit leukocyte adhesion to endothelial cells. We report on the
      first enantioselective total synthesis of the (9S, 18R)-diastereomer of this
      macrocyclic polyene lactam. Key elements of the synthesis are i) the synthesis of
      the required chiral building blocks by employing readily accessible building
      blocks from the chiral pool, that is, (S)-malic acid and (R)-hydroxyisobutyric
      acid, ii) assembly of a linear polyene precursor by means of Wittig and Horner
      olefination reactions as key C-C bond-forming transformations, iii) ring closure
      by means of a vanadium-mediated pinacolisation reaction and iv) conversion of the
      generated cis-diol into a (Z)-olefin to complete the entire polyene system of the
      natural product. Attempts to close the macrocyclic ring by a macrolactamisation,
      a double Stille coupling or direct olefination in a McMurry reaction failed.
      Crucial to the successful completion of the synthesis was the correct
      orchestration of the final steps. It was necessary to first deprotect the
      intermediate formed after macrocycle formation and to generate the sensitive
      heptaene system in the last step by means of a Corey-Hopkins sequence.

PMID- 11531124
TI  - Ab initio calculations on the mechanism of the oxidation of the hydroxymethyl
      radical by molecular oxygen in the gas phase: a significant reaction for
      environmental science.
AB  - The mechanism of the gas-phase reaction of *CH2OH+O2 to form CH2O+HO2* was
      studied theoretically by means of high-level quantum-chemical electronic
      structure methods (CASSCF and CCSD(T)). The calculations indicate that the
      oxidation of *CH2OH by O2 is a two-step process that goes through the peroxy
      radical intermediate *OOCH2OH (1), formed by the barrier-free radical addition of
      *CH2OH to O2. The concerted elimination of HO2* from 1 is predicted to occur via
      a five-membered ringlike transition structure of Cs symmetry, TS1, which lies
      19.6 kcalmol(-1) below the sum of the energies of the reactants at 0 K. A four
      membered ringlike transition structure TS2 of Cs symmetry, which lies 13.9
      kcalmol(-1) above the energy of the separated reactants at 0 K, was also found
      for the concerted HO2* elimination from 1. An analysis of the electronic
      structures of TS1 and TS2 indicates that both modes of concerted HO2* elimination
      from 1 are better described as internal proton transfers than as intramolecular
      free-radical H-atom abstractions. The intramolecular 1,4-H-atom transfer in 1,
      which yields the alkoxy radical intermediate HOOCH2O*, takes place via a puckered
      ringlike transition structure TS3 that lies 13.7 kcalmol(-1) above the energy of
      the reactants at 0 K. In contrast with earlier studies suggesting that a direct H
      atom abstraction mechanism might occur at high temperatures, we could not find
      any transition structure for direct H-atom transfer from the OH group of *CH2OH
      to the O2. The observed non-Arrhenius behavior of the temperature dependence of
      the rate constant for the gas-phase oxidation of *CH2OH is ascribed to the
      combined effect of the initial barrier-free formation of the *OO-CH2OH adduct
      with a substantial energy release and the existence of a low-barrier and two high
      barrier pathways for its decomposition into CH2O and HO2*.

PMID- 11531125
TI  - Benzoannelated cis,cis,cis,trans-[5.5.5.6]fenestranes: syntheses, base lability,
      and flattened molecular structure of strained epimers of the all-cis series.
AB  - Tribenzofenestranes possessing the strained cis,cis,cis,trans-[5.5.5.6]
      fenestrane skeleton have been synthesized from cis-2,6-diphenylspiro[cyclohexane
      1,2'-indane]-1',3'-diols by two-fold cyclodehydration, in striking analogy to the
      strategy used previously to construct the stereoisomeric all-cis
      tribenzo[5.5.5.6]fenestranes from the corresponding trans-diphenylspirodiols. In
      this manner, both of the parent hydrocarbons, all-cis-tribenzo[5.5.5.6]fenestrane
      3 and cis,cis,cis,trans-tribenzo[5.5.5.6]fenestrane 4, have been made accessible
      from the spirodiketones 5 and 6, respectively. The C6-functionalized derivatives
      of 4-cis,cis,cis,trans-fenestranol 9 and cis,cis,cis,trans-fenestranone 12-were
      prepared through cis-diphenylspirotriol 8 and cis-diphenyldispiroacetaldiol 11,
      by using the same strategy. The cis,cis,cis,trans-[5.5.5.6]fenestrane framework
      readily epimerizes to the more stable all-cis isomers under basic conditions, but
      is stable under neutral or acidic conditions. For example, cis,cis,cis,trans
      fenestranone 12 yielded all-cis fenestrane 3 under Wolff-Kishner conditions, but
      cis,cis,cis,trans-isomer 4 under Clemmensen conditions. Epimerization was also
      circumvented by radical-induced desulfurization of fenestrane dithiolane 15 with
      nBu3SnH/AIBN, producing 4 in excellent yields. A single-crystal X-ray structure
      analysis of 4 revealed that, in accordance with force field and semi-empirical MO
      calculations, the extra strain of the benzoannelated cis,cis,cis,trans
      [5.5.5.6]fenestratriene framework [Estrain(4)-Estrain(3)=46 kJmol(-1)] is due
      both to the almost perfect boat conformation of the six-membered ring and to
      considerable bond angle widening at the central, non-bridged C4b-C15d-C11b unit
      (121 degrees). H/D exchange experiments with the cis,cis,cis,trans hydrocarbon 4
      under basic conditions demonstrated that the strain-induced epimerization to 3
      occurs through direct deprotonation of the "epimeric" benzylic bridgehead C7a-H
      bond, which was found to be more acidic than the two C-H bonds at the
      benzhydrylic bridgeheads.

PMID- 11531126
TI  - Structural transformations in a crystal during the photochemical reaction of 2
      benzyl-5-benzylidenecyclopentanone.
AB  - The studies presented are the first example in which the substrate and product
      molecules were monitored separately over many stages during the chemical reaction
      progress in a crystal to understand the reaction path of the molecules in detail
      during the whole transformation. The BBCP, 2-benzyl-5-benzylidenecyclopentanone,
      single crystal was irradiated without any destruction over several steps. After
      each of step the X-ray structure with a different substrate/product ratio and
      with a disorder was determined. The study revealed that the photochemical [2+2]
      cycloaddition reaction of BBCP in a crystal does not exhibit cooperative
      character and can be regarded as of the first-order. During the transformation
      the product molecules do not adopt the position of the molecules in the final
      pure dimer crystal, but move gradually and smoothly in this direction. The
      movement of the molecules was also observed for the substrate. This remarkable
      behaviour of the product and reactant molecules bears a rotational component. The
      distance between reaction centres of adjacent BBCP substrate molecules decreases
      fluently with the progress of the reaction, but it does not get smaller than a
      sum of van der Waals radii.

PMID- 11531127
TI  - Incorporation of a molecular hinge into molecular tweezers by using tandem
      cycloadditions onto 5,6-dimethylenenorbornene.
AB  - Site-selective 1,3-dipolar coupling at the norbornene pi-bond of 5,6
      dimethylenenorbornene 1 yields cycloadducts with an end-fused 1,3-diene system
      which have been reacted with N=N (or C=C) dienophiles to produce ribbon
      molecules, in which the internal diazacyclohexene (or cyclohexene) subunits are
      capable of acting as conformational hinges. Direct coupling of 5,6
      dimethylenenorbornene with 1,3,4-oxadiazoles or dual coupling with
      bis(cyclobutene epoxides) afforded bis(1,3-dienes) that diastereoselectively
      react with dienophiles to produce new, conformationally mobile, molecular
      tweezers.

PMID- 11531128
TI  - Contingency perception and misperception in infancy: some potential implications
      for attachment.
AB  - A theoretical analysis is presented in which the four major attachment patterns
      (A, B, C, and D) are viewed as adaptations to particular forms of early
      contingency experience. The author proposes that human infants analyze
      contingency experience on the basis of two computations of conditional
      probability, one prospective and one retrospective. Ideally, when these
      computations do not agree, the direction of disagreement provides information as
      to how the infant should adjust effective behavior and/or how potential
      contingent consequences should be redefined. The author also proposes that the
      specific patterns of insecure attachment (A, C, and D) are a result of parental
      responsiveness that is by nature inconsistent or out of balance and that the
      infant interprets this imbalance as his or her misperception of a balanced
      contingency. The observed symptoms of attachment insecurity are seen as
      consistent with specific attempts by infants to adjust behavior and/or
      discrimination according to the direction of imbalance in conditional
      probabilities they have experienced in interactions with their caretakers.

PMID- 11531129
TI  - Infants' detection of contingency: a cognitive-neuroscience perspective.
AB  - Advances in developmental cognitive neuroscience have generated important and
      interesting data that are relevant to infants' perception of contingencies. The
      author discusses concepts of "binding" (i.e., the binding of stimulus properties
      across space, and binding of events across time) within the context of the
      cognitive-neuroscience approach to learning. Issues relevant to infant
      contingency perception are also addressed. Previously published data on infant
      contingency perception and discrimination learning from the author's laboratory
      are reinterpreted in terms of these binding concepts, as well as the development
      of the neural substrates that presumably underlie the perception of stimulus
      attributes and temporal redundancy.

PMID- 11531130
TI  - Discovering self through other: infants' preference for social contingency.
AB  - Infants' early self-knowledge is acquired most readily in social interactions,
      because others respond to infants in contingent ways. Recent findings are
      described, which indicate that infants are sensitive not only to social
      contingency early in life but also to particular levels of social contingency
      found in their parental interactions. Implications of these sensitivities for
      developmental risks and advancements are discussed.

PMID- 11531131
TI  - Social contingency detection and infant development.
AB  - The developmental origins and determinants of social contingency detection are
      discussed. Based on recent research, the author proposes that the origins of
      social contingency detection correspond to the early propensity developing in the
      first 6 months of life to differentiate between what pertains to the self (i.e.,
      one's own body) and what pertains to others. Furthermore, from the second month
      of life, what infants appear to gain from contingency detection while interacting
      with others is a sense of shared experience or intersubjectivity. Research
      suggests that although the development of intersubjectivity is a central feature
      of infant behavior and development, the meaning of contingency detection, hence
      the source of intersubjectivity, changes radically between birth and 18 months of
      age. In general, it is proposed that the origins and determinants of social
      contingency detection must be construed in relation to (1) the developing sense
      of self in infancy, (2) the infant's developing sense of reciprocity with others,
      and (3) the infant's developing sense of participation with others. The author
      concludes by proposing a relevant map of changing social stances adopted by
      infants in the course of early development.

PMID- 11531132
TI  - From social expectations to social cognition in early infancy.
AB  - The end of the first year marks an important social-cognitive transition for
      human infants. Around this time, they start to engage in a new variety of joint
      attentional behaviors not clearly present in the preceding months. These new
      social behaviors are thought to index infants' understanding of intentions in
      others-an understanding that ultimately gives way to an active participation in
      human culture. Given the importance of such understanding, the question is from
      where infants' new social-cognitive repertoire may originate. Well before the
      emergence of joint attention, infants are sophisticated social beings, readily
      able to form expectations about others and inclined to relate differentially to
      them. The author focuses on the potential connection between social expectations
      developing in the context of early face-to-face interactions and the social
      cognitive changes taking place by the end of the first year of life.

PMID- 11531133
TI  - Experimental protocols for investigating relationships among mother-infant
      interaction, affect regulation, physiological markers of stress responsiveness,
      and attachment.
AB  - Gergely and Watson's (1996) social biofeedback theory of parental affect
      mirroring applies the conditional probability model of contingency perception to
      parent-child interactions. Infants are first evaluated at birth on neurological
      and temperament measures. Infants are also evaluated at 6 and 12 months on tasks
      that study social interactional determinants, infant attachment, and
      physiological reactions. The Strange Situation is completed at 12-15 months of
      age. The authors describe how the combination of these experimental and
      observational procedures allows specific developmental hypotheses to be
      investigated about the quality of contingent parental affect regulation,
      sensitivity to internal states, and security of attachment.

PMID- 11531134
TI  - Cognitive perspectives on unresolved loss: insights from the study of PTSD.
AB  - The authors begin by reviewing recent work on attachment disorganization and its
      association with parental unresolved loss. They draw connections between this
      literature and recent theoretical and empirical work on trauma and posttraumatic
      stress disorder (PTSD). They propose that unresolved loss involves intrusion and
      avoidance phenomena similar to those of PTSD. Specifically, they develop a model
      based on the notion that unresolved loss involves the failure to integrate
      representations of self and the world following a loss. The features of
      unresolved loss can be understood as emerging as a result of the activation of
      unintegrated representations of the loss experience and cognitive and behavioral
      avoidance processes. In this model, the sudden intrusion of memories, cognitions,
      and emotions associated with the loss automatically captures attention and
      initiates behavioral dispositions that are incompatible, and hence interfere,
      with caregiving behavior. Lack of attentional resources and incompatible response
      tendencies can also result from safety behaviors directed at avoiding the
      perceived negative consequences of activating trauma memory. The authors propose
      that these processes offer a novel way of understanding the disturbances in
      behavior and speech that are evident in parents who are classified as unresolved
      with respect to loss in the Adult Attachment Interview.

PMID- 11531135
TI  - A contingency-based approach to the etiology of 'disorganized' attachment: the
      'flickering switch' hypothesis.
AB  - The authors present a new approach to the etiology of disorganized attachment
      based on contingency detection theory. According to this view, the relevant
      common factor in parental maltreatment and unresolved loss that leads to
      disorganized attachment has to do with the type of "deviant contingency
      environment" that both of these conditions generate. In such environments,
      infants experience periods of being in control followed by periods of sudden loss
      of control over the caregiver's behavior. The authors hypothesize that this
      adversely affects the developmental unfolding of the infant's innate "contingency
      detection module" (Gergely & Watson, 1999), which normally involves a
      maturational shift around 3 months from an initial attention bias for perfectly
      contingent stimulation to an emerging preference for less-than-perfect social
      contingencies. The periodically changing controllability of abusive and
      dissociating "unresolved" attachment figures is hypothesized to block this
      process and to lead to the defensive fixation of a dysfunctional "flickering
      contingency switch" mechanism with two dominant and competing target positions
      (self-oriented vs. other-oriented). This results in the dissociative style of
      attention and behavioral organization characteristic of disorganized infant
      attachment. The authors summarize the preliminary results of an empirical study
      that provides support for this model in 6.5-month-old infants using a modified
      Still-Face situation (the Mirror Interaction Situation). The study demonstrates
      differential emotional and behavioral reactions to sudden loss of maternal
      contingency and a specific interest in exploring the perfectly contingent self
      image in the mirror in infants who at 12 months become categorized as
      "disorganized" in the Strange Situation.

PMID- 11531136
TI  - The obscure object of desire: 'nearly, but clearly not, like me': contingency
      preference in normal children versus children with autism.
AB  - The author describes the central role of contingency detection in early
      socioemotional development. It has been proposed (Gergely & Watson, 1999) that
      infants are innately equipped with a complex perceptual mechanism, the
      "contingency detection module," which functions to establish the primary
      representation of the bodily self as well as the later orientation toward
      reactive social objects. According to the "contingency switch" model, the target
      value of the module that is initially genetically set to preferentially explore
      perfectly response-contingent stimulation is "switched" at around 3 months toward
      a preference for less-than-perfect social contingencies. It is hypothesized that
      the primary cause of childhood autism is a genetic defect, due to which the
      normal process of switching contingency preference at around 3 months does not
      take place. Preliminary results from an experimental study to test this model are
      reported. The study contrasts the preferential reactions of normal children and
      children with autism to perfect versus imitative (high-but-imperfect)
      contingencies. The results provide support for the contingency switch hypothesis
      of the etiology of childhood autism.

PMID- 11531137
TI  - The human genome and the representational world: the role of early mother-infant
      interaction in creating an interpersonal interpretive mechanism.
AB  - The author discusses the interrelationship of genetic predisposition, experiences
      in the first 3 years of life, and psychological disturbance in later development.
      The current emphasis on genetic determinism has led to the popular misconception
      that early relationships with caregivers play a relatively minor role in the
      development of mental disorder. The author argues that early attachment
      relationships matter because the mental mechanism moderating the expression of
      individual genotypes is intrinsically linked to the relationship with the primary
      caregiver. Attachment in infancy has the primary evolutionary function of
      generating a mind capable of inferring things about other people's minds, their
      thoughts, ideas, motivations, and intentions. The child needs to be able to make
      these inferences to arrive at a representation of the self in terms of a set of
      stable and generalized intentional attributes. Awareness of others' thoughts and
      feelings is necessary to ensure social collaboration. This formulation
      underscores the vital importance of parent training for the normal emotional and
      cognitive development of a child and the prevention of major psychological
      disturbance.

PMID- 11531138
TI  - Measuring beyond the microscope field of view using digital images in squamous
      cell carcinoma of the lip.
AB  - OBJECTIVE: To study the impact of using digital images for measuring the size of
      the tumors, assisting with the prognostic evaluation of carcinomas of the oral
      mucosa. STUDY DESIGN: The depth of invasion of 12 cases of squamous cell
      carcinoma of the lower lip was assessed through a microscope and through digital
      images. All measurements of depth of invasion were assessed in a direction
      orthogonal to the lip surface. First, assessment of depth of invasion was done at
      the microscope, using an eyepiece reticule with an engraved scale. Second, depth
      of invasion was assessed by digital images, using a program module developed to
      assist pathologists with linear measuring. When the depth of the tumor was larger
      than the field of view at the proper magnification, several images were taken to
      include the whole area of invasion. The images were finally mounted in a single
      image and the depth of invasion measured. RESULTS: The results show positive and
      negative differences between assessments when assessing depths of < 2 mm. At
      greater depths (> or = 2 mm), the difference was always negative, showing that
      for deep invasion, measurements of longer distances were always performed on
      digital images. CONCLUSION: Measurements with digital images beyond the field of
      view at proper magnification could sig nificantly alter the diagnostic and
      prognostic assessment made using the microscope.

PMID- 11531139
TI  - Prognostic significance of nuclear morphometry in superficial bladder cancer.
AB  - OBJECTIVE: To evaluate the significance of nuclear morphometry in predicting the
      clinical course in superficial (pTa and pT1) bladder cancer. STUDY DESIGN: The
      study included 73 patients with superficial transitional cell carcinoma of the
      bladder who were followed for a median of 21 months (range, 1-90). Nuclear
      morphometry was performed by a computer-assisted image analyzer system on
      hematoxylineosin-stained histologic sections and characterized by five nuclear
      variables: area, perimeter, major and minor diameter, and form factor. Patient
      charts and microscopic slides were reviewed to record tumor stage, grade and
      size. Tumor proliferative activity was assessed by immunohistochemical staining
      with Ki-67 antibody. RESULTS: None of the morphometric variables showed a
      significant relation to tumor progression and recurrence. Higher values of mean
      nuclear area, perimeter, and major and minor diameter were significantly related
      to higher grade and proliferative activity. Mean nuclear area and minor diameter
      were associated with advanced stage. Of established prognostic factors, only
      histologic grade was significant in predicting progression. CONCLUSION: The
      results suggest that nuclear morphometry may be valuable in determining
      proliferative activity and may be well correlated with histologic grade in
      superficial bladder cancer. However, like many other potential prognostic
      factors, it seems to be unreliable in predicting clinical behavior.

PMID- 11531141
TI  - Digital microscopy for multiparameter FISH imaging.
AB  - Fluorescence in situ hybridization (FISH) allows the direct localization of DANN
      and RNA sequences on chromosomes, in cells and in tissue. The technique is based
      on hybridization between target sequences of single-strand DNA of chromosomes or
      cell nuclei with marked complementary specimens. The signal is amplified using
      fluorochrome-marked specific antibodies and made visible under a microscope.
      Signals from painted chromosomes, stained subchromosomal regions or localized
      single probes are generally visible when an epifluorescence microsope is used. In
      order to view and display different fluorochromes, single filter sets, as well as
      double and triple bandpass filters, are in use. For multiple fluoroscence
      imaging, lenses with high numerical aperture, mostly oil immersion systems, are
      recommended. In conventional photomicrography, triple exposure on high-speed film
      (e.g., 400-1,000 ASA) is more or less the limitation. Opto=electronic methods
      using a CCD and laser summing techniques have considerably extended the
      application range of multiple fluorescence techniques. By means of digitized
      images, simultaneous detection of multiple-labelled objects and ratio imaging up
      to 24 colors are possible today. Current FISH approaches are based on chromosome
      painting probes to distinguish all 24 chromosomes by their unique spectral
      signatures.

PMID- 11531140
TI  - Mathematical morphologic segmentation dedicated to quantitative
      immunohistochemistry.
AB  - OBJECTIVE: To develop automatic segmentation sequences for fully automated
      quantitative immunohistochemistry of cancer cell nuclei by image analysis. STUDY
      DESIGN: The study focused on the automated delineation of cancer cell lobules and
      nuclei, taking breast carcinoma as an example. A hierarchic segmentation was
      developed, employing mainly the chaining of mathematical morphology operators.
      The proposed sequence was tested on 22 images of various situations, collected
      from 18 different cases of breast carcinoma. A quality control procedure was
      applied, comparing the automated method with manual outlining of cancer cell foci
      and with manual pricking of cancer cell nuclei. RESULTS: Good concordance was
      found between automated and manual segmentation procedures (90% for cancer cell
      clumps, 97% for cancer cell nuclei on average), but the rate of false positive
      nuclei (small regions labeled as nuclei by the segmentation procedure) could be
      relatively high (11% on average, with a maximum of 35%) and can result in
      underestimation of the immunostaining ratio. CONCLUSION: This study examined a
      preliminary approach to automated immunoquantification, limited to automated
      segmentation without any color characterization. The automated hierarchic
      segmentation presented here leads to good discrimination of cancer cell nuclei at
      the chosen magnification.

PMID- 11531142
TI  - Morphometric characteristics of cell proliferation and p53 expression in
      development of experimentally induced respiratory tumors.
AB  - OBJECTIVE: To study, under controlled conditions, the applicability of automated
      image analysis of immunohistochemical markers as an indicator of development and
      progression in tobacco component-induced tumors in the respiratory tract. STUDY
      DESIGN: Amount, location, size, shape and intensity of staining of proliferating
      cell and p53 antigen in chemically induced precursors and squamous cell carcinoma
      of the hamster lung were determined by computer-assisted morphometry. RESULTS:
      The total expression of proliferating cell nuclear antigen (PCNA) and p53
      expression increased consistently during the formation of papillomas and squamous
      cell carcinomas of the larynx, trachea, bronchi and lungs. Individual
      preneoplastic cells in epithelial dysplasia expressed PCNA staining, increasing
      with increasing cell size and optical density, indicating antibody- staining
      intensity, in relation to the increased degree of cellular atypia. In malignant
      tumors, cell size decreased with decreasing differentiation, while antibody
      staining intensity remained unchanged. The increased alterations in cell shape
      and percent PCNA-positive cells observed in dysplastic epithelium and squamous
      cell carcinomas were statistically significant using Spearman's correlation
      coefficient. Squamous cell carcinomas consisted of two tumor cell populations
      with different cell shapes, and PCNA and p53 staining intensity. Altering
      measurement conditions-antibody threshold levels, size of measured area and
      repeating measurements-showed computer-assisted image analysis to give sensitive,
      reliable and consistent results. CONCLUSION: Computer-assisted analysis of
      immunohistochemical staining showed high sensitivity and reproducibility;
      however, the results depended upon the method of study.

PMID- 11531143
TI  - Automated nuclear image morphometry on fine needle aspiration smears of malignant
      round cell tumors.
AB  - OBJECTIVE: To analyze nuclear image morphometry in fine needle aspiration
      cytology smears of different groups of malignant round cell tumors (MRCTs) to
      evaluate its diagnostic role. STUDY DESIGN: In this study there were 55 cases of
      MRCT, consisting of 18 Ewing's sarcoma (EW), 10 neuroblastoma (NB), 5 non
      Hodgkin's lymphoma (NHL), 6 rhabdomyosarcoma (RMS), 4 peripheral neuroectodermal
      tumor (PNET), 8 Wilm's tumor (WT), 2 retinoblastoma (RB) and 2 undifferentiated
      round cell tumor (URCT). A Leica image cytometer with Quantimet 600 software
      (Leica, Cambridge, U.K) was used to measure nuclear area, nuclear diameter,
      nuclear perimeter, nuclear convex perimeter (CP), nuclear roundness and nuclear
      convex area on hematoxylin and eosin-stained cytologic smears. At least 100 cells
      were studied in each case. RESULTS: The RB group of tumors showed the highest
      mean nuclear area (NA), convex area (CA), CP, diameter (D), perimeter (P) and
      roundness (R). RMS had the highest mean CA, and URCT had the highest mean
      roundness. ANOVA was performed on the tumors and showed significant differences
      for all the variables in all the groups (P < .000). All the morphometric data
      (except roundness) were significantly different in RMS versus all other MRCTs
      except RB. Similarly, morphometric data on WT were also significantly different
      from that on NHL. Most of the morphometric data (except CA and R) showed
      significant differences between RB and all other MRCTs except RMS. PNET, EW and
      NB could not be differentiated with those variables. CONCLUSION: RMS and RB could
      successfully be differentiated from all other MRCTs with the help of morphometry.
      It was not possible to differentiate RMS and RB by image cytometry (ICM) since
      the ICM data overlapped in those two groups. It was possible to differentiate WT
      and NHL with ICM. Nuclear ICM was not significantly different in the NB, PNET and
      ES groups, and probably ICM would not be very helpful to differentiate these
      groups of MRCT.

PMID- 11531144
TI  - Quantification of histochemical staining by color deconvolution.
AB  - OBJECTIVE: To develop a flexible method of separation and quantification of
      immunohistochemical staining by means of color image analysis. STUDY DESIGN: An
      algorithm was developed to deconvolve the color information acquired with red
      green-blue (RGB) cameras and to calculate the contribution of each of the applied
      stains based on stain-specific RGB absorption. The algorithm was tested using
      different combinations of diaminobenzidine, hematoxylin and eosin at different
      staining levels. RESULTS: Quantification of the different stains was not
      significantly influenced by the combination of multiple stains in a single
      sample. The color deconvolution algorithm resulted in comparable quantification
      independent of the stain combinations as long as the histochemical procedures did
      not influence the amount of stain in the sample due to bleaching because of stain
      solubility and saturation of staining was prevented. CONCLUSION: This image
      analysis algorithm provides a robust and flexible method for objective
      immunohistochemical analysis of samples stained with up to three different stains
      using a laboratory microscope, standard RGB camera setup and the public domain
      program NIH Image.

PMID- 11531145
TI  - Measurement of chemopreventive efficacy in skin biopsies.
AB  - OBJECTIVE: To explore methods suitable for quantitative assessment of the
      efficacy of chemopreventive intervention. STUDY DESIGN: High-resolution imagery
      of nuclei from the suprabasal and basal cell layers of sun-damaged skin were
      recorded. There were 10 cases. A shave biopsy was taken from an area of clearly
      evident solar keratosis before and after treatment with 2-difluoromethyl
      dlornithine (DFMO) and from the colateral forearm, treated with a placebo. A
      number of karyometric variables were computed and combined to derive marker
      features that provided a numeric measure of the degree of nuclear deviation from
      normal. RESULTS: DFMO treatment was effective overall in reducing the degree of
      nuclear abnormality seen in the biopsies; in 8 of the 10 cases there was a
      significant improvement. The placebo-treated arm did not show a statistically
      different abnormality from the untreated arm. CONCLUSION: Karyometric analysis
      can provide numeric measures that allow documentation of statistically
      significant regression of actinic keratotic lesions following treatment with
      DFMO.

PMID- 11531146
TI  - Flow and image cytometry in thymic neoplasia: correlation with clinical outcome.
AB  - OBJECTIVE: To compare nuclear DNA by flow (FCM) and image cytometry (ICM) in
      thymic neoplasms and to relate results to clinical outcome. STUDY DESIGN: DNA
      ploidy of 44 thymomas and 6 thymic carcinomas was studied by FCM and ICM of
      single nuclear suspensions from paraffin blocks. RESULTS: By FCM, 33 thymomas
      (75%) and one thymic carcinoma (17%) were diploid; 6 thymomas (14%) and 4 thymic
      carcinomas (67%) were aneuploid. By ICM, 36 thymomas (82%) were diploid; 7
      thymomas (16%) and 6 thymic carcinomas (100%) were aneuploid. Mean follow-up in
      44 cases was 46.2 months (range, 1-162). Ten patients with persistent/recurrent
      disease included four with thymic carcinoma, who died of the disease (two
      aneuploid by both techniques, two aneuploid by ICM with unsatisfactory/diploid
      FCM). Four had invasive thymoma and recurrence after 13-150 months (two diploid
      and two aneuploid by both methods), one had diploidy and noninvasive thymoma that
      recurred at 92 months, and one had an epithelial thymoma that recurred at 144
      months (aneuploid by FCM, diploid by ICM). CONCLUSION: The results obtained in
      this preliminary, retrospective study show a high concordance between FCM and
      ICM; aneuploidy correlated with poor outcome by both methodologies. While these
      findings are encouraging, larger numbers of cases will be needed to define the
      role of FCM and ICM in predicting outcome in thymic tumors.

PMID- 11531147
TI  - Regulation of prostaglandin synthesis in the human uterus.
AB  - Prostaglandins are important regulators of many aspects of reproductive processes
      from ovulation, fertilization and pregnancy recognition to labor and parturition.
      These biologically potent compounds are members of the large family of
      eicosanoids, derived from polyunsaturated fatty acids, principally arachidonic
      acid, found in the membrane phospholipids of virtually every cell of the human
      body, accounting for the ubiquity of prostaglandins, which act in a paracrine or
      autocrine fashion via discrete receptors. The availability of specific
      prostaglandins in various cells and tissues depends on the presence and activity
      of specific enzymes that convert a common precursor to the end product, as well
      as on the rate of enzymatic or spontaneous inactivation of the bioactive
      compounds. Here we offer a brief review of the regulation of prostaglandin
      generation in human uterine tissues, focusing on their role in labor and
      parturition at term and preterm.

PMID- 11531148
TI  - Fetal serum levels of insulin, growth hormone and insulin-like growth factor-I in
      concordant and discordant twin gestations.
AB  - OBJECTIVE: To examine the role of insulin, growth hormone and insulin-like growth
      factor (IGF)-I in concordant and discordant twin pairs. METHODS: Umbilical cord
      serum samples were obtained from 20 twin pairs with weight discordancy (intertwin
      birth weight difference > 20%) and from 20 concordant twins (intertwin birth
      weight difference < 20%), both groups of similar gestational age, gravidity, and
      parity. The serum samples were analyzed for the levels of IGF-I, growth hormone
      and insulin in both maternal and fetal compartments. RESULTS: Among the group of
      discordant twins, the normally grown twin, in all cases, had significantly higher
      cord serum IGF-I levels than their growth-restricted co-twin (108 +/- 73 ng/ml
      vs. 39 +/- 24 ng/ml; p < 0.01). There were no significant intertwin differences
      in the cord blood IGF-I levels in the concordant twin pairs (87 +/- 44 vs. 88 +/-
      48 ng/ml; p = 0.986). Insulin and growth hormone levels did not correlate with
      intertwin birth weight differences. CONCLUSION: These data demonstrate that IGF-I
      is important in the regulation of both normal and restricted fetal growth in
      utero, and its action appears to be, at least in part, through an endocrine
      action. The precise role of growth hormone and insulin in fetal growth
      restriction remains uncertain.

PMID- 11531149
TI  - Insulin-meal interval and short-term glucose fluctuation in tightly controlled
      gestational diabetes mellitus.
AB  - OBJECTIVE: To study the effect of two insulin-meal intervals on short-term
      glucose fluctuations in tightly controlled gestational diabetes mellitus (GDM).
      METHODS: We performed a prospective and paired study in 11 Japanese GDM women
      requiring insulin for good glycemic control during the third trimester. The women
      were subjected to test two insulin-meal intervals: 15 min and 30 min. Both
      regimens were examined in each patient in random order, 2 days apart. Blood
      glucose was measured by an automated glucose monitor every 2 min. Short-term
      glucose fluctuations of the two observations were analyzed by two-way ANOVA for
      repeated measurements with a post hoc t test (p < 0.05). Data were expressed as
      mean +/- SD. RESULTS: Daily glucose profiles of the two groups showed that their
      glycemic controls on the days of observation were good and that the two glucose
      profile curves were superimposable. A transient decrease in glucose (nadir 62 +/-
      6 mg/dl) was observed at 6-10 min of meal ingestion in the 30-min regimen, which
      was significantly different from the glucose fluctuations during the 15-min
      regimen. The 2-h postprandial glucose levels were similar in both experiments.
      CONCLUSIONS: In women with tightly controlled GDM during the third trimester,
      insulin-meal intervals of 15 min are beneficial when compared with 30-min
      intervals, in that they avoid preprandial hypoglycemia without increasing 2-h
      postprandial hyperglycemia.

PMID- 11531150
TI  - Magnesium, zinc and iron levels in pre-eclampsia.
AB  - OBJECTIVE: To determine the change in erythrocyte and plasma magnesium, plasma
      zinc and serum iron concentrations in pre-eclampsia. METHODS: Twenty women with
      pre-eclampsia and 20 control subjects matched for gestational age were examined.
      The levels of magnesium, zinc and iron in all subjects were measured by flame
      atomic absorption spectrometry. In the pre-eclamptic women, who were supplemented
      with magnesium salts, these measurements were repeated after delivery. RESULTS:
      The intraerythrocytic magnesium levels before supplementation were significantly
      lower in the pre-eclamptic patients than in the healthy pregnant women (0.98 +/-
      0.15 vs. 1.35 +/- 0.30 mmol/l; p < 0.001) and increased (to 1.25 +/- 0.25 mmol/l)
      after treatment with magnesium. The plasma magnesium and zinc, and the serum iron
      concentrations were not significantly different between the pre-eclamptic and the
      healthy pregnant women. CONCLUSIONS: Our results suggest that low cellular
      magnesium levels in women with pre-eclampsia may contribute to the development of
      hypertension in these patients, and that the measurements of plasma zinc and
      serum iron concentrations are of doubtful clinical value in the management of pre
      eclampsia.

PMID- 11531151
TI  - Ovine fetal swallowing: expression of preterm neurobehavioral rhythms.
AB  - OBJECTIVE: Fetal swallowing contributes importantly to amniotic fluid volume
      regulation and fetal gastrointestinal maturation. Near-term ovine fetal
      swallowing occurs in discrete bouts of activity (at approximately 30-min
      intervals) in association with fetal electrocortical voltage changes. Thus,
      swallowing rhythms have been hypothesized to be entrained to fetal
      neurobehavioral states. In the preterm ovine fetus, electrocortical activity does
      not demonstrate differentiation into high- and low-voltage periods until 120-130
      days' gestation. We sought to quantify patterns of preterm (114 days, 0.75
      gestation) ovine fetal swallowing activity and volume, and, in view of the lack
      of electrocortical pattern changes, to explore whether swallowing activity was
      regulated by an independent central pacemaker. METHODS: Six singleton ovine
      pregnancies were chronically prepared with fetal and maternal femoral artery and
      vein catheters. Biparietal electrocortical electrodes were placed on the fetal
      skull. Following a minimum 5-day recovery period, fetuses were studied at 114 +/-
      1 days. Patterns of fetal swallowing behavior were quantified by computer
      analysis of laryngeal-esophageal electromyography (EMG) and thoracic esophageal
      fluid flow during a 12-h period. RESULTS: Esophageal fluid flow was
      bidirectional, although antegrade flow predominated, leading to an average fluid
      acquisition rate of 13 +/- 3 ml/h (7.3 +/- 1.8 ml/h per kg) during the 12-h study
      (302 +/- 87 ml/day). Propagated esophageal EMG activity, representing coordinated
      'swallows', averaged 56 +/- 6 swallows/h and correlated well with net esophageal
      fluid flow. 'Bouts' of swallowing activity (> or = 3 swallows/min) averaged 9 +/-
      1 swallows/bout, lasted 1.8 +/- 1.4 min and accounted for 31 +/- 4% of the
      swallowed volume. Despite the absence of fetal electrocortical high-voltage/low
      voltage transitions, there was a 26.1 +/- 3.9-min interval between periods of
      swallowing bout activity. CONCLUSIONS: Preterm (0.75 gestation) ovine fetal
      volume swallowed (302 ml/day) and volume swallowed for body weight (175 ml/day
      per kg) was significantly less than that previously noted at 0.85 gestation (831
      ml/day, 274 ml/day per kg, respectively; p < 0.05) although the rates of
      swallowing activity were similar. The presence of swallowing bout activity at
      periodic intervals, in the absence of electrocortical differentiation, suggests
      an intrinsic central pacemaker regulating preterm fetal neurobehavior.

PMID- 11531152
TI  - The degree of antenatal ventriculomegaly is related to pediatric neurological
      morbidity.
AB  - OBJECTIVE: Our hypothesis was that the degree of antenatally diagnosed cerebral
      ventriculomegaly is related to aneuploidy, perinatal mortality and long-term
      neurological morbidity. METHODS: Ninety-one cases of ventriculomegaly identified
      from 1 June 1994 to 1 July 1999 were examined for prenatal, intrapartum and
      neonatal complications. Pediatric follow-up was reviewed for infants with
      ventriculomegaly from birth up to as long as 4 years. Minor neurological
      morbidity was defined as a score of 70-80 on the clinical adaptive test/clinical
      linguistic and auditory milestone scale and included mild motor or language
      delay. Major morbidity included a score of < 70, evidence of cerebral palsy, or
      seizure disorder. The incidence of neurological complications was compared, on
      the basis of the degree of ventriculomegaly, with group 1 being > 10-15 mm and
      group 2 being > 15 mm. RESULTS: Twenty-seven cases (18 with neural tube defects
      and nine with holoprosencephaly) were excluded. Among the remaining 64 patients,
      39 had a ventricular diameter of > 10-15 mm and comprised group 1. Five of the 39
      cases (12.8%), all with other ultrasound anomalies, elected to terminate. The
      incidence of aneuploidy in group 1 was 14.2%. Among the 19 cases with isolated
      ventriculomegaly, 17 (89%) were normal and two (11%) had minor neurological
      morbidity. In group 1 there were two cases associated with cytomegalovirus (CMV)
      infection. Of the 25 cases in group 2, eight (32%), all with other ultrasound
      anomalies, elected to terminate. The incidence of aneuploidy in group 2 was
      17.4%. For the nine cases with isolated ventriculomegaly of > 15 mm, one (11%)
      was normal (p < 0.001), five (56%) had minor neurological morbidity requiring a
      ventriculoperitoneal shunt (p = 0.035), and three (33%) had major neurological
      morbidity (p = 0.045) when compared to cases of isolated ventriculomegaly in
      group 1. There was one case of CMV infection in group 2. All perinatal deaths in
      both groups were associated with other anomalies. CONCLUSIONS: Amniocentesis to
      determine karyotype and the presence of CMV is warranted for all cases of
      ventriculomegaly of > 10 mm. The degree of antenatal ventriculomegaly is related
      to pediatric neurological morbidity and, when it is > 15 mm, it is associated
      with an increase in abnormal neurological development.

PMID- 11531153
TI  - The effect of variable heart rate decelerations on intraventricular hemorrhage
      and other perinatal outcomes in preterm infants.
AB  - OBJECTIVE: We investigated the hypothesis that repetitive variable heart rate
      decelerations in labor are associated with an increased incidence of neonatal
      complications in premature infants. METHODS: This was a retrospective case
      control study. Singleton fetuses weighing between 750 and 2500 g at 25-35 weeks'
      gestation were considered for the study. Fetuses delivered by Cesarean section
      prior to labor were excluded. Heart rate traces were retrieved from an electronic
      archive and were assessed for the presence of variable decelerations. Cases had
      at least three variable decelerations in the hour prior to delivery and were
      matched 1:1 with controls for gestation, sex and birth weight. RESULTS: A review
      of 6500 deliveries yielded 41 matched pairs. The groups were compared for the
      following outcomes. Measures of acute morbidity were cord pH at delivery, 5-min
      Apgar score and resuscitation; measures of chronic morbidity were
      intraventricular hemorrhage, periventricular leukomalacia, necrotizing
      enterocolitis and death. There was no difference in measures of acute morbidity
      between the groups. The incidence of chronic morbid outcome measures in the cases
      was six (15%) vs. one (2.5%) in controls (p = 0.01). CONCLUSIONS: This study
      suggests that variable decelerations in preterm infants are associated with
      chronic morbidity, particularly intraventricular hemorrhage through a mechanism
      independent of fetal acidemia. Further study is required to determine whether
      these infants would benefit from early Cesarean section.

PMID- 11531154
TI  - Multiple courses of antenatal betamethasone and cognitive development of mice
      offspring.
AB  - OBJECTIVE: To measure the effect of multiple courses of antenatal betamethasone,
      used for lung maturation, on long-term cognition of mice offspring. METHODS:
      Forty gravid CD-1 mice were randomly assigned to receive one of four treatments
      (n = 10 per group): 0.1 mg betamethasone or saline placebo, given subcutaneously
      either once daily on gestational days 13-16 or twice daily on days 14 and 15.
      This dose of betamethasone given on gestational day 14 causes fetal lung
      maturation in mice. Three offspring per gender in each litter underwent standard
      cognitive tasks as juveniles and as adults. Analysis of variance or Kruskal
      Wallis testing was used to compare data. RESULTS: Learning acquisition and memory
      were indistinguishable between the betamethasone-exposed and the corresponding
      placebo-exposed offspring when performing the following tasks: juvenile runway
      with adult memory, adult water runway and Morris spatial maze. This lack of
      difference in task performance between treatment groups persisted after
      controlling for gender and for each multiple-course regimen. CONCLUSION: Multiple
      courses of antenatal corticosteroids did not impact the mouse offsprings' long
      term learning and memory.

PMID- 11531155
TI  - Early discharge revisited: problems encountered with the home visit follow-up
      after the liberalization of eligibility criteria.
AB  - OBJECTIVE: To determine how changes in eligibility criteria for early discharge
      affected quality and costs of home nursing follow-up care for Medicaid patients.
      METHODS: A nurse screened women delivering vaginally to determine eligibility for
      discharge at 24-47 h. Maternal criteria were a vaginal delivery, no serious
      medical problems, > or = 8 h after bilateral tubal ligation and, if 24 h
      postpartum, by 21.00 on day of discharge. Newborn criteria were 36 weeks'
      gestation or more, 2000 g or greater and a normal examination at 24 h of age. By
      48 h after discharge, a nursing visit was ordered for each mother and newborn.
      Nursing consultations were tracked and later entered into a database linked to
      hospital financial data. RESULTS: Of 3133 vaginal deliveries occurring from 1
      August 1997 to 31 January 1999, eligibility criteria allowed 1799 mothers (58%)
      and 1587 newborns (51%) to be discharged early. Medical problems were rarely
      detected at follow-up (1% mothers, 2% newborns). To perform the increased number
      of visits, more personnel were hired and home nursing costs rose 150%. Despite
      the increased staff and costs, 19 mothers (1%) and ten newborns (0.6%) were lost
      to follow-up and 25 mothers (1%) and 20 newborns (1%) were visited beyond 72 h
      after discharge. CONCLUSIONS: Liberal changes in maternal and newborn eligibility
      criteria did not adversely affect the quality of home nursing follow-up care
      following early discharge. For hospitals performing a large number of early
      discharges, follow-up care using only a home nursing visit may be too expensive
      and difficult to organize. Alternative follow-up plans, such as clinic visits or
      phone calls, may also need to be utilized.

PMID- 11531156
TI  - Determination of fetal occiput position by ultrasound during the second stage of
      labor.
AB  - OBJECTIVE: To investigate whether ultrasonography is superior to vaginal
      examination for determination of fetal occiput position during the second stage
      of labor. METHODS: We conducted a prospective cohort study of 44 parturients.
      During the second stage of labor, an attending obstetrician performed a vaginal
      examination to detect fetal occiput position. This was followed by combined
      abdominal and perineal ultrasound examination. The two methods were compared to
      the true position. Results were analyzed using Student's t test for quantitative
      parameters. McNemar's and Fisher's exact tests were applied in order to examine
      differences between the study groups. RESULTS: The error rate in detecting fetal
      occiput position was significantly lower using the ultrasound technique (6.8%)
      compared to vaginal examination (29.6%, p = 0.011). Parity, maternal body mass
      index or fetal weight had no influence on the error rate. CONCLUSIONS:
      Ultrasonographic determination of the fetal position is an accurate technique and
      is superior to vaginal examination.

PMID- 11531157
TI  - Fetal seizures: case report and literature review.
AB  - We report a case of fetal seizures secondary to lissencephaly. Among the 13
      published cases of fetal seizures, including ours, diagnosed at a mean
      gestational age of 35.5 weeks (range 20-42), a fetal heart rate tracing was
      available in ten and showed a normal pattern in three, low variability in two and
      repetitive decelerations or bradycardia in five. The most common cause of fetal
      seizures was congenital anomalies (seven of 13), mainly of the central nervous
      system (six of seven). Outcome among the 11 liveborn neonates included death by 6
      months of age in eight cases, and mental or motor delay in three.

PMID- 11531158
TI  - Intrapartum spontaneous rupture of liver hemangioma.
AB  - A 28-year-old pregnant woman presented at 35 weeks' gestation to obstetric triage
      with vague abdominal symptoms, stable vital signs and a non-reassuring fetal
      heart rate. During Cesarean section, intraperitoneal hemorrhage was noted,
      secondary to spontaneous rupture of a liver hemangioma. We present the
      perioperative management of a patient with liver hemangioma, along with a review
      of the literature.

PMID- 11531159
TI  - Metabolic interrelationships between liver and skeletal muscle in pathological
      states.
AB  - The present review focuses on the metabolic interrelationships between liver and
      muscle in pathological states associated with catabolic conditions. Carbohydrate,
      fat and nitrogen metabolism between the parenchymal liver and skeletal muscle are
      considered and interrelated together with the possible mediators involved in
      pathological conditions.

PMID- 11531160
TI  - Differentially expressed CC3/TIP30 and rab11 along in vivo and in vitro
      intestinal epithelial cell crypt-villus axis.
AB  - We have previously shown that transforming growth factor-beta1 (TGF-beta1) is
      involved in the fibroblast-induced organization and differentiation of
      transformed phenotypically crypt-like T84 intestinal epithelial cells into
      absorptive enterocyte-like cells, when cultured within a three-dimensional
      collagen gel. We have used differential display polymerase chain reaction to find
      genes that are either up- or downregulated by TGF-beta in the T84 cells cultured
      in three-dimensional collagen gel and then studied how these in vitro
      differentially expressed genes are expressed in vivo in the small intestinal
      crypt-villus axis. We found that the TGF-beta1-treated T84 cells, like the villus
      tip enterocytes, expressed increased levels of CC3/TIP30 when compared to the
      undifferentiated cells. Furthermore, the expression of rab11 showed the opposite
      pattern, being higher in the undifferentiated cells both in vivo and in vitro. We
      conclude that the three-dimensional cell culture model where TGF-beta induces
      organization and differentiation of secretory T84 epithelial cells makes it
      possible to find up- and downregulated transcripts that also play a role in the
      human small intestinal crypt-villus axis.

PMID- 11531161
TI  - Effects of Sheng-Mai injection on the PRPP synthetase activity in BFU-es and CFU
      es from bone marrows of mice with benzene-induced aplastic anemia.
AB  - 160 Kunming mice were divided at random into 3 groups. Group 1: normal control
      (40 mice). Group 2: aplastic anemia (AA) control (60 mice); benzene inhalation
      was carried out for 2.5 months and sterilized normal saline was injected i.p. for
      another 6 weeks. Group 3: treated AA (60 mice); benzene was administered by
      inhalation in a similar manner, Sheng-Mai Injection (SMI) was administered i.p.
      for 6 weeks after the AA models were established. SMI is a famous Chinese
      traditional prescription of Panax ginseng C.A. Meyer (0.1 g/ml), Ophiopogon
      japonicus (Thunb.) Ker-Gawl (0.312 g/ml) and Fructus Schisandrae (0.158 g/ml).
      Activities of phosphoribosylpyrophosphate (PRPP) synthetase in BFU-Es and CFU-Es
      were estimated by ion pair reversed phase HPLC (IPrHPLC). Accompanying the sharp
      drop in counts of erythroid progenitor cells, the PRPP synthetase activity in CFU
      Es of AA mice was reduced significantly (P<0.01), whereas there were no
      remarkable changes of this enzyme activity in their BFU-Es compared with the
      control group. Both the counts of erythroid progenitor cells and PRPP synthetase
      activity in CFU-Es returned nearly to normal levels following treatment with SMI
      of mice in Group 3 (P<0.01). Our results suggest that the attenuation of PRPP
      synthetase activity in peripheral erythrocytes of AA patients may originate from
      the weakening of activity of this enzyme in CFU-Es from their bone marrow. The
      impairment of PRPP formation would explain ATP depletion and disorders of energy
      metabolism in AA erythrocytes. SMI can distinctly increase the reduced quantity
      of erythroid progenitor cells and promote rapid restoration of PRPP synthetase
      activity in CFU-Es of AA mice.

PMID- 11531162
TI  - Inhibitory effects of fluvastain and its metabolites on the formation of several
      reactive oxygen species.
AB  - We investigated the inhibitory effects of fluvastain (FV) and its metabolites (M
      2, M-3, M-4, M-5, and M-7) on the formation of several reactive oxygen species
      (ROS), such as singlet oxygen (1O2), superoxide anion (O2-), hydroxy radical
      (*OH), hypochlorite ion (OCL-), and linoleic acid peroxide (LOO*). Inhibitory
      effects of pravastatin (PV), simvastatin (SV), probucol (PR) and alpha-tocopherol
      (TOC) were also tested. The inhibitory effects of 5-hydroxy FV (M-2) and 6
      hydroxy FV (M-3) on the formation of 1O2, O2-, *OH, and OCL- were strongest.
      Scavenging of 1O2 by M-4, M-5, (+)-FV, and (-)-FV was also noted. The inhibitory
      effects of (+)-FV on the formation of 1O2 were comparable to those of (-)-FV, PV,
      SV, PR and M-7 had little or no inhibitory effect on the formation of several
      ROS. In conclusion, FV and its metabolites, particulary M-2 and M-3, have the
      potential to protect against oxidative stress mediated by several ROS.

PMID- 11531163
TI  - Inhibition of glucose transport by cyclic GMP in cardiomyocytes.
AB  - Recent evidence points to a potential role of cyclic GMP (cGMP) in the control of
      cardiac glucose utilization. The present work examines whether the glucose
      transport system of cardiac myocyte is a site of this cGMP-dependent regulation.
      Treatment of isolated rat cardiomyocytes (for 10 min) with the membrane-permeant
      cGMP analogue 8-(4-chlorophenylthio)-cGMP (8-p-CPT-cGMP, 200 microM) caused a
      decrease in glucose transport in non-stimulated (basal) myocytes, as well as in
      cells stimulated with insulin or with the mitochondrial inhibitor oligomycin B by
      up to 40%. An inhibitory effect was also observed with another cGMP analogue (8
      bromo-cGMP), and in cells stimulated by hydrogen peroxide or anoxia. In contrast,
      8-p-CPT-cAMP (200 microM), or the beta-adrenergic agonist isoprenaline (which
      increases cAMP levels) did not depress glucose transport, and even potentiated
      the effect of insulin. Blockade of endogenous cGMP formation with the guanylate
      cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 10 microM)
      significantly increased basal and insulin-dependent glucose transport (by 25%),
      whereas addition of the guanylate cyclase activator 3-(5'-hydroxymethyl-2'furyl)
      1-benzylindazol (YC-1, 30 microM) produced a depression of glucose transport (by
      20%). Confocal laser scanning microscopic studies revealed that cGMP partially
      prevents the insulin-induced redistribution of the glucose transporter GLUT4 from
      intracellular stores to the cell surface. These observations suggest that the
      glucose transport system of cardiomyocytes represents a metabolic target of
      inhibition by cGMP, and that this regulation occurs at the level of the
      trafficking of glucose transporters.

PMID- 11531164
TI  - Calcium-sensitive potassium channel inhibitors antagonize genistein- and daidzein
      induced arterial relaxation in vitro.
AB  - Estradiol-17beta relaxes rabbit coronary artery rings via large conductance Ca2+
      activated K+-channels (K(Ca)). Genistein and daidzein are plant-derived estrogen
      like compounds. The aim of the present study was to investigate whether potassium
      channels participate in the genistein- and daidzein-induced arterial relaxation
      like they do in the case of estradiol-17beta. Endothelium-denuded superior
      mesenteric arterial rings from non-pregnant Wistar female rats were used. At a
      concentration of 10 microM, estradiol-17beta, genistein and daidzein relaxed
      noradrenaline precontracted arterial rings, (58 +/- 4%, 45 +/- 5% and 31 +/- 3%,
      respectively; (n=6-8)). Genistein- and daidzein-induced relaxations were
      inhibited both by iberiotoxin (1-10 nM) and charybdotoxin (30 nM), the
      antagonists of large conductance Ca2+-activated K+-channels (K(Ca)). Estradiol
      17beta-induced relaxation was reduced by iberiotoxin (30 nM). Estradiol-17beta-
      and daidzein-induced relaxations were also decreased by apamin (0.1-0.3 microM),
      an antagonist of small conductance Ca2+-activated K+-channels. The antagonists of
      voltage-dependent K+-channels (K(V)) (4-aminopyridine), ATP-sensitive K+-channels
      (K(ATP)) (glibenclamide), or inward rectifier K+-channels (KIR) (barium) had no
      effect on the relaxation responses of any of the compounds studied. Estrogen
      receptor antagonist tamoxifen did not inhibit the relaxations. In conclusion, in
      the noradrenaline precontracted rat mesenteric arteries, the relaxations caused
      by estradiol-17beta, genistein and daidzein were antagonized by large and small
      conductance K(Ca)-channel inhibitors, suggesting the role of these channels as
      one of the relaxation mechanisms.

PMID- 11531165
TI  - Cerebral protein kinase C and its mRNA level in apolipoprotein E-deficient mice.
AB  - It is known that protein kinase C (PKC) activity may be one of the fundamental
      cellular changes associated with memory function. Apolipoprotein E (apoE)
      deficiency causes cholinergic deficits and memory impairment. ApoE-deficient
      mouse has been employed as a serviceable model for studying the relation between
      apoE and the memory deficit induced by cholinergic impairment. Brain-fatty acid
      binding protein (b-FABP) might be functional during development of the nervous
      system. Peroxisome proliferator-activated receptor (PPAR) is involved in the
      early change in lipid metabolism. We investigated the alterations not only in
      cerebral PKC activity, but also in the gene expressions of PKC-beta, brain-FABP
      and PPAR-alpha in apoE-deficient mice. The results showed that there was a lower
      cerebral membrane-bound PKC activity in the apoE-deficient mice than in its wild
      type strain (C57BL/6). But there were no significant differences in cytosolic PKC
      activity. PKC-beta, b-FABP and PPAR-alpha mRNA expressions in cerebrum were
      lowered in apoE-deficient mice. These findings may be involved in the dysfunction
      of the brain neurotransmission system in apoE-deficient mouse. Alternatively,
      these results also suggest that cerebral apoE plays an important role in brain
      PKC activation by maintaining an appropriate expression of b-FABP and PPAR-alpha
      mRNAs.

PMID- 11531166
TI  - Antagonism of morphine-induced antinociception by tetrandrine is dependent on
      serotonergic mechanisms.
AB  - 'Tetrandrine (TET), a non-specific calcium antagonist, inhibited morphine-induced
      antinociception in the tail-flick test in mice. This study was undertaken to
      assess the mechanism of the antagonism of morphine-induced antinociception by
      TET. Morphine-induced antinociception was prevented by pretreatment with TET in
      the tail-flick but not in the tail-pinch tests carried out in mice and this
      antagonism was abolished by pretreatment of a serotonin precursor, 5
      hydroxytryptophan (5-HTP), but not by the pretreatment of a noradrenaline
      precursor, L-dihydroxyphenylalanine (L-DOPA), in the tail-flick test. These
      results indicate that serotonergic mechanisms are involved in the antagonism of
      morphine-induced antinociception by TET. On the other hand, the development of
      morphine-induced analgesic tolerance was not prevented by TET. This result, in
      agreement with other reports, also indicates the possible dissociation of
      morphine analgesic effect from its tolerance-inducing effect. In addition, TET
      suppressed the 5-hydroxytryptamine (5-HT)-induced head twtch response. This
      result provides additional evidence that TET may modulate serotonergic function
      and the antagonism of morphine-induced antinociception by TET is dependent on
      serotonergic mechanisms.

PMID- 11531167
TI  - Pharmacological profile of hydroxy fasudil as a selective rho kinase inhibitor on
      ischemic brain damage.
AB  - The neuroprotective property and the effects on hemodynamics of hydroxy fasudil,
      an active metabolite of an antispastic drug, fasudil, were examined. In rats,
      hydroxy fasudil was found following intravenous infusion or intraperitoneal
      administration of fasudil, and the maximum plasma concentration of hydroxy
      fasudil was approximately 25 or 40% of the parent drug, respectively. The i.v.
      administration of hydroxy fasudil produced significant increases in regional
      cerebral blood flow in dogs. Hydroxy fasudil relaxed the KCl, PGF2alpha or U
      46619-induced contraction in canine basilar or middle cerebral arterial strips,
      concentration-dependently. The neuroprotective property of hydroxy fasudil was
      examined on delayed neuronal death in gerbils. Hydroxy fasudil (3 mg/kg)
      significantly protected against the ischemia-induced neuronal loss. To further
      clarify the effect on neurological impairments, hydroxy fasudil was tested in a
      rat model of microembolization stroke. Intravenous administration of hydroxy
      fasudil improved neurological functions, significantly reduced the size of the
      infarct area and prevented the accumulation of neutrophils. The present findings
      suggest that hydroxy fasudil has an efficacy to improve the hemodynamic function
      and to inhibit neutrophil-mediated damage, and contributes to the potency and
      long duration of the cytoprotective properties of fasudil on ischemic brain
      damage, and also suggest a critical role for rho kinase in the pathogenesis of
      cerebral ischemic injury, and the potential utility of rho kinase inhibitor as a
      therapeutic agent in stroke.

PMID- 11531169
TI  - Dementia: the "mind-snatcher".

PMID- 11531168
TI  - Acetaminophen distribution in the rat central nervous system.
AB  - Based on the evidence that the antinociceptive effects of acetaminophen could be
      mediated centrally, tissue distribution of the drug after systemic administration
      was determined in rat anterior and posterior cortex, striatum, hippocampus,
      hypothalamus, brain stem, ventral and dorsal spinal cord. In a first study, rats
      were treated with acetaminophen at 100, 200 or 400 mg/kg per os (p.o.), and drug
      levels were determined at 15, 45, 120, 240 min by high performance liquid
      chromatography (HPLC) coupled with electrochemical detection (ED). In a second
      study, 45 min after i.v. administration of [3H]acetaminophen (43 microCi/rat;
      0.65 microg/kg), radioactivity was counted in the same structures, plus the
      septum, the anterior raphe area and the cerebellum. Both methods showed a
      homogeneous distribution of acetaminophen in all structures studied. Using the
      HPLC-ED method, maximal distribution appeared at 45 min. Tissue concentrations of
      acetaminophen then decreased rapidly except at the dose of 400 mg/kg where levels
      were still high 240 min after administration, probably because of the saturation
      of clearance mechanisms. Tissue levels increased with the dose up to 200 mg/kg
      and then leveled off up to 400 mg/kg. Using the radioactive method, it was found
      that the tissue/blood ratio was remarkably constant throughout the CNS, ranking
      from 0.39 in the dorsal spinal cord to 0.46 in the cerebellum. These results,
      indicative of a massive impregnation of all brain regions, are consistent with a
      central antinociceptive action of acetaminophen.

PMID- 11531170
TI  - Pemphigus.

PMID- 11531171
TI  - Alzheimer's disease: an overview.

PMID- 11531172
TI  - Depression or dementia?

PMID- 11531173
TI  - Featured CME topic: dementia. Fact sheets.

PMID- 11531174
TI  - Featured CME topic: dementia. Medication update.

PMID- 11531175
TI  - Coding and reimbursement for dementia.

PMID- 11531176
TI  - Pemphigus in the southeastern United States.
AB  - BACKGROUND: Our purpose was to review the course and management of pemphigus
      treated at a tertiary care center in the southeastern United States. METHODS: We
      describe 30 patients seen at the Emory Clinic from January 1992 to July 1999.
      RESULTS: Equal numbers of men and women from different ethnic backgrounds were
      affected. Pemphigus vulgaris was more common than pemphigus foliaceous. Pain,
      sore throat, and pruritus were the most common presenting symptoms. The mean
      diagnostic delay was 6 months in patients with pemphigus foliaceous and 4.5
      months in patients with pemphigus vulgaris. Hospitalization was required in 47%
      of patients. Adjuvant therapy in addition to systemic orticosteroids was required
      in 93%. Herpes gingivostomatitis occurred in 33%. Clinical or total remission was
      obtained in 33%. CONCLUSIONS: Pemphigus occurs in multiple ethnic groups in the
      southeastern United States. Appropriate treatment is frequently delayed by lack
      of prompt diagnosis. The complications of pemphigus and its therapy were
      significant.

PMID- 11531178
TI  - Reducing the incidence of sudden infant death syndrome in the Delta region of
      Mississippi: a three-pronged approach.
AB  - Since the "Back to Sleep" campaign in 1994, which encouraged positioning infants
      on their backs for sleeping, the incidence of sudden infant death syndrome (SIDS)
      has decreased dramatically in the United states but remains high in some rural
      Mississippi communities. We discuss some of the hypotheses and etiologic factors
      of SIDS. The high incidence of SIDS in the Delta region of Mississippi could be
      dramatically reduced, primarily through an intensified Back to Sleep campaign.
      Furthermore, the importance of health education in increasing breast-feeding
      rates and reducing passive smoke exposure rates in this community is emphasized.

PMID- 11531177
TI  - Secondary prevention of cerebral ischemia in patent foramen ovale: systematic
      review and meta-analysis.
AB  - BACKGROUND: Therapy for patent foramen ovale (PFO), found with increased
      frequency in the setting of stroke in the young, is controversial. We compiled a
      synthesis of the literature on therapeutic options for PFO and stroke. METHODS:
      Searching MEDLINE (1966 to 1999), published abstracts, and bibliographies of
      primary and review articles, we identified five retrospective cohort studies that
      compared at least two different treatment options (antiplatelet therapy,
      warfarin, or surgery). Outcomes data on mode of therapy and recurrent stroke were
      abstracted, and pooled analysis was done using a random effects model. RESULTS:
      Warfarin was superior to antiplatelet therapy in preventing recurrent ischemic
      events (odds ratio [OR] 0.37; 95% confidence interval [CI], 0.23 to 0.60).
      Surgical PFO closure was comparable to warfarin treatment (OR 1.19; 95% CI, 0.62
      to 2.27). CONCLUSION: Available data suggest that warfarin is superior to
      antiplatelet therapy and comparable to surgical PFO closure for the prevention of
      recurrent cerebral ischemic events from paradoxical embolism.

PMID- 11531179
TI  - Racial/ethnic health disparities in South Carolina and the role of rural locality
      and educational attainment.
AB  - BACKGROUND: The prevalence of selected health indicators were compared among the
      Catawba Indians, African Americans, and whites in South Carolina, considering the
      possible role of rural locality and education. METHODS: Catawba members were
      respondents of a 1998 survey (N = 808). Other South Carolina residents were
      respondents of the 1995-1997 Behavioral Risk Factor Survey (4,150 whites and
      1,413 African Americans). Prevalence of cardiovascular disease, diabetes,
      hypertension, overweight, poor health, smoking, physical inactivity, and poor
      diet were compared among the racial/ethnic groups. Logistic regression analyses
      were conducted within strata of urban/rural locality and education to determine
      whether these factors were associated with the adverse health indicators.
      RESULTS: Both Catawba and African Americans had higher prevalence of diabetes,
      hypertension, overweight, poor health, physical inactivity, and poor diet than
      whites. In addition, prevalence of diabetes, poor health, smoking, and poor diet
      were higher among the Catawba than among African Americans. Restricting the
      analyses to comparisons within urban/rural locality had little effect, whereas
      restricting the analyses to comparisons by education level eliminated many of the
      disparities among those with low education. CONCLUSIONS: Prevalence of chronic
      disease and adverse health behavior are higher among the Catawba than among other
      residents of South Carolina, especially compared with white residents.

PMID- 11531180
TI  - Nontubercular mycobacterial pulmonary infection in immunocompetent men.
AB  - BACKGROUND: Nontubercular mycobacteria (NTM) are increasingly recognized to cause
      lung disease in immunocompetent patients. We studied the occurrence of pulmonary
      infection due to NTM in immunocompetent men. METHODS: We retrospectively analyzed
      all sputum mycobacterial cultures at our institution over a 5-year period. Charts
      were reviewed to identify patients who met the American Thoracic Society's
      criteria for mycobacterial pulmonary infection. RESULTS: From the 7,380 sputum
      mycobacterial cultures obtained, 46 male patients had NTM identified. Forty-two
      patients were immunocompetent. Five of these patients were found to have NTM--2
      with Mycobacterium kansasii, 2 with Mycobacterium avium-intracellulare, and 1
      with Mycobacterium gordonae. All 5 patients responded to antimycobacterial
      therapy. CONCLUSION: Twelve percent of our population of immunocompetent men from
      whom NTM were isolated from sputum were infected. This study should alert the
      clinician that NTM cause treatable pulmonary disease in immunocompetent men.

PMID- 11531181
TI  - William Osler's influence on the career of Tinsley Randolph Harrison.
AB  - In 1957, I was graduated from what was then the Medical College of Alabama, a
      division of the University of Alabama. It was a privilege and honor to be on Dr.
      Harrison's service on two occasions during my last 2 years of medical school. He
      was the most influential role model during my student years and has remained so
      throughout my professional life. I have always benefitted from his writings, his
      profound philosophical approach to medicine, and his numerous aphorisms. Only in
      later years have I come to know of the tremendous influence of William Osler on
      Tinsley Harrison through his father, William Groce Harrison. Unfortunately,
      Tinsley Harrison never knew Sir William Osler because he died the year Tinsley
      Harrison began his second year of medical school at Johns Hopkins. This
      connection is interesting from many standpoints. For instance, Osler advised
      Groce Harrison to make Tinsley a "teacher of medicine" when Tinsley was only 3
      years old. Through the advice of his father, Tinsley followed the Oslerian
      tradition throughout his life. This paper presents several similarities between
      Osler and Harrison.

PMID- 11531182
TI  - Retrohepatic vena cava and juxtahepatic venous injuries.
AB  - The daunting mortality encountered with retrohepatic vena cava and juxtahepatic
      venous trauma is testimony to the difficulties inherent in their management. For
      a successful outcome, the operating surgeon must be able to rapidly identify the
      nature of the injury and tailor the choice of procedure accordingly. Atriocaval
      shunting, balloon shunting, sequential vascular clamping, and perihepatic packing
      are all methods of treatment with which the surgeon must be familiar. In this
      review, we present a case of this injury caused by a gunshot wound. This serves
      as a useful starting point for a discussion of the techniques available for
      addressing this injury.

PMID- 11531183
TI  - Gout, bradycardia, and hypercholesterolemia after renal transplantation.
AB  - Approximately 17,000 solid organ transplantations are done annually in the United
      States. Increasingly, care of these patients will be provided by primary care
      physicians. In this report, we illustrate the complexity of common medical
      problems in a patient who had cellulitis and who had had a cadaveric renal
      transplantation 10 years earlier. Immunosuppressive therapy was cyclosporine (100
      mg twice a day) and prednisone (10 mg once a day). The patient's hospital course
      was complicated by acute gout and symptomatic bradycardia. In both instances,
      usual treatment--full-dose indomethacin for gout and withholding verapamil for
      bradycardia--could have had significant interaction with the cyclosporine. At the
      time of discharge, a therapeutic plan for long-term management of
      hypercholesterolemia included possible drug interactions with cyclosporine. The
      potential for drug toxicity in the transplant patient necessitates careful
      monitoring of immunosuppressive drug levels. Ongoing communication with the
      transplant center is also needed.

PMID- 11531184
TI  - Retroperitoneal fibrosis: unusual cause of low back pain.
AB  - Retroperitoneal fibrosis (RPF) is an uncommon collagen vascular disease with a
      male predominance. Back pain with no specific radiation pattern is common, and
      bilateral obstructive uropathy, potentially reversible, is frequently associated
      with RPF. We report a case of RPF and review its diagnosis and management.

PMID- 11531185
TI  - Recurrent ascites and pleural effusions after surgery for early-stage endometrial
      adenocarcinoma.
AB  - A case of massive postoperative ascites in a woman treated for endometrial cancer
      is reported. A workup for typical causes of ascites yielded negative results,
      prompting a more detailed analysis of the patient's condition. Hypothyroidism was
      discovered. After correction of the hypothyroidism, the ascites slowly resolved.
      Since myxedema is an uncommon cause of ascites, this is usually a diagnosis of
      exclusion. However, hypothyroidism must be ruled out to prevent unnecessary and
      possibly inappropriate treatments for ascites.

PMID- 11531186
TI  - Pancreatic trauma: an unusual soccer injury.
AB  - We report a case of pancreatic duct laceration and acute pancreatitis resulting
      from blunt abdominal trauma sustained in a youth soccer match. Since this sports
      injury is unusual, a brief discussion of soccer injuries and of the management of
      pancreatic trauma in childhood is provided.

PMID- 11531187
TI  - Primary vulvar adenocarcinoma of cloacogenic origin.
AB  - A 43-year-old woman who had a vulvar mass associated with mild discomfort was
      found to have a rare primary vulvar adenocarcinoma of probable cloacal origin.
      The tumor was contiguous with the surface epithelium of the vulva and was a well
      to moderately differentiated adenocarcinoma of colonic type. Stains of the
      neoplastic cells were positive for both acid and neutral mucin, and periodic acid
      Schiff (PAS) was positive after diastase reaction. The neoplastic cells were
      strongly positive for carcinoembryonic antigen, broad spectrum cytokeratin, and p
      53 antigen. Clinical evaluation failed to show any primary tumor in colon, lung,
      or breast. The patient was disease free 18 months after operation.

PMID- 11531188
TI  - Clinical ethics, living and dying: new challenges for changing times.

PMID- 11531189
TI  - Ethical dilemmas in home health care: a social work perspective.
AB  - The survey in this article examined several factors related to the frequency and
      difficulty of resolving four ethical conflicts in a national sample of 364 home
      health care social workers. Ethical conflicts regarding the assessment of mental
      competence, self-determination, and access to services were moderately frequent
      and difficult to resolve, whereas conflicts over implementing advance directives
      were infrequent and not difficult to resolve. Each ethical conflict involved
      multiple stakeholders. Multiple regression analyses revealed significant
      predictors of the frequency and difficulty of resolving the ethical conflicts.
      Implications for practice and administration in home health care and social work
      education are discussed.

PMID- 11531190
TI  - Values underlying end-of-life decisions: a qualitative approach.
AB  - The purpose of the study discussed in this article was to reveal the values that
      would receive priority attention when considering end-of-life decisions. Nineteen
      elderly Israelis and their 28 family members participated in individual
      interviews that were analyzed using a hermeneutic phenomenological method.
      Analysis of the transcripts indicated that participants considered a unique set
      of value priorities that raised different considerations in each off our domains
      of life: physical-biological, social-psychological, familial, and societal. Three
      transcendent values crossed all four life domains: dignity, quality of life, and
      quality of death. These value considerations are useful information for social
      workers who consult patients and family members at times of end-of-life
      decisions.

PMID- 11531191
TI  - Ethical issues in the social worker's role in physician-assisted suicide.
AB  - This article presents the results of an exploratory study of social workers'
      views on physician-assisted suicide (PAS), situations in which PAS would be
      favored, and whether there is a difference in education or training on mental
      health issues, ethics, or suicide between social workers who favor PAS and those
      who oppose PAS. A questionnaire was administered to a convenience sample of 66
      social workers in South Carolina. The authors raise questions about the training
      in mental health issues, ethics, and suicide that social workers have received to
      prepare them to work with clients making this end-of-life decision. Implications
      for social work practice and suggestions for future research are presented.

PMID- 11531192
TI  - Successful interprofessional collaboration on the hospice team.
AB  - Despite the holistic approach inherent in the hospice philosophy, social work may
      be viewed in hospices as ancillary or secondary to medicine. Social work, in
      turn, may have a lack of training and sensitivity about other professions'
      expertise and values and as a result be unprepared to collaborate across the
      cultural boundary that exists between professions. Barriers to full use of all
      disciplines on the interdisciplinary team include lack of knowledge of the
      expertise of other professions, role blurring, conflicts arising from differences
      among professions in values and theoretical base, negative team norms, client
      stereotyping, and administrative issues. This article outlines the barriers and
      proposes solutions to address them.

PMID- 11531193
TI  - Hoarding by elderly people.
AB  - Although hoarding has been studied in adults, little is known about problems of
      hoarding by elderly people. This study used a structured telephone interview with
      elder services providers to investigate hoarding behaviors in relation to
      functional impairment, cognitive deficits, and physical and psychological
      conditions in 62 elderly clients. Most elderly hoarders were female, unmarried,
      and lived alone. Extensive clutter was associated with significant impairment,
      interfering with basic hygiene, and posing a serious physical threat for many
      elderly clients. Clients were rarely insightful about their collecting and often
      resisted change, rendering interventions generally ineffective. Never-married
      status was associated with more severe hoarding and greater impairment and
      possibly with worse outcomes of intervention efforts. Health and mental health
      implications of hoarding by elderly people and implications for treatment are
      discussed.

PMID- 11531194
TI  - Cultural competence versus cultural chauvinism: implications for social work.

PMID- 11531195
TI  - Ending clinical relationships with people with schizophrenia.
AB  - The potential for the social worker-client relationship to contribute to
      therapeutic outcomes is not always apparent with clients who have schizophrenia.
      Their cognitive impairments often make it difficult for these clients to regulate
      interpersonal boundaries and for social workers to connect with them. Clinical
      practice is enhanced, however, by recognizing that severely impaired clients have
      the capacity and desire for relationships with service providers and others. The
      manner in which the clinical relationship ends is important for maintaining
      clinical gains and determining whether the client will risk investing in future
      relationships. The purpose of this article has been to sensitize social workers
      to the delicate nature of managing the endings of those relationships.

PMID- 11531196
TI  - A call to action: patients' access to clinical trials.

PMID- 11531197
TI  - Clinical trials: a wider lens.

PMID- 11531198
TI  - Clinical trials: a wider lens 2.

PMID- 11531199
TI  - Clinical trials: opportunities and responsibilities.

PMID- 11531200
TI  - Hindsight, foresight, and having it both ways: a rejoinder to R. L. Spitzer.
AB  - Using the methods of philosophical analysis, we provide a rejoinder to R. L.
      Spitzer's (2001) response to our own consideration of the DSMs first published in
      1994. Then as now, our major contention has been that the DSM contents and
      process have been insufficiently explicit in their various value commitments,
      choices, and decisions. Spitzer raises four major points in his commentary,
      concerning our claims about the "value naivete" of past DSMs, his contention that
      the goals of DSM-III and III-R were not "inherently" in conflict, about our
      allegations of the DSM architects preferring reliability over validity, and
      various DSM critics' failure to offer a viable alternative to the DSMs. We
      address each of Spitzer's main points in turn, appealing to Spitzer's own work
      while acknowledging his leadership role in addressing value issues in mental
      disorder classification.

PMID- 11531201
TI  - Is clinical depression distinct from subthreshold depressive symptoms? A review
      of the continuity issue in depression research.
AB  - Resolving whether subthreshold depressive symptoms exist on a continuum with
      unipolar clinical depression is important for progress on both theoretical and
      applied issues. To date, most studies have found that individuals with
      subthreshold depressive symptoms resemble cases of major depressive disorder
      along many important dimensions (e.g., in terms of patterns of functional
      impairment, psychiatric and physical comorbidity, familiality, sleeping EEG, and
      risk of future major depression). However, such manifest similarities do not rule
      out the possibility of a latent qualitative difference between subthreshold and
      diagnosable depression. Formal taxonomic analyses, intended to resolve the
      possibility of a latent qualitative distinction, have so far yielded
      contradictory findings. Several large-sample latent class analyses (LCA) have
      identified latent clinical and nonclinical classes of unipolar depression, but
      LCA is vulnerable to identification of spurious classes. Paul Meehl's taxometric
      methods provide a potentially conservative alternative way to identify latent
      classes. The one comprehensive taxometric analysis reported to date suggests that
      self-report depression symptoms occur along a latent continuum but exclusive
      reliance on self-report depression measures and incomplete information regarding
      sample base rates of depression makes it difficult to draw strong inferences from
      that report. We conclude that although most of the evidence at this time appears
      to favor both a manifest and latent continuum of unipolar depression
      symptomatology, several important issues remain unresolved. Complete resolution
      of the continuity question would be speeded by the application of both taxometric
      techniques and LCA to a single large sample with a known base rate of lifetime
      diagnosed depressives.

PMID- 11531202
TI  - Traumatic experiences and the mental health of Senegalese refugees.
AB  - The purpose of our study was to conduct a preliminary investigation into the
      experiences and mental health of Senegalese refugees. Although research has
      established that refugees are more prone to psychiatric illnesses than the
      general population, little has been written about West African refugees. Our
      focus was on adult refugees (18 years of age and older) from the Casamance region
      of Senegal. A total of 80 participants (39 women, 41 men) were randomly selected
      from refugee camps in The Gambia. The Harvard Trauma Questionnaire and the
      Hopkins Symptom Checklist-25 were used to assess levels of traumatization and
      mental health status. Typical of refugees of war, participants reported suffering
      a large number of various traumas. High prevalence rates of anxiety, depression,
      and posttraumatic stress disorder were also found in this group. A substantial
      mental health problem exists within the Senegalese refugee population that may
      signify a potential human crisis.

PMID- 11531203
TI  - Evaluations of others by borderline patients.
AB  - This study investigated evaluations of other people in specific emotional
      situations by patients with borderline personality disorder (BPD). BPD patients
      (N = 16), control patients with cluster C personality disorder (PD; N = 12) and
      normal controls (N = 15) saw film clips with emotional themes centering on
      abandonment, rejection and abuse, hypothesized to be specific for borderline
      pathology. Subjects wrote down their spontaneous reactions to six film
      personalities, divided over three clips, including what they thought to be
      characteristic traits of these persons. Spontaneous reactions were coded on two
      dimensions, based on earlier studies by Westen and colleagues: a) affect-tone of
      ascribed qualities and b) complexity of evaluations of people. The number of
      trait dimensions constituted the third scale. The overall pattern of findings
      suggests that the BPD group, as well as the cluster C group, show poorly
      differentiated evaluations with a low number of dimensions. Thus, this seems
      characteristic for personality disorders in general. The BPD group shows a lower
      affect-tone, reflecting a stronger tendency to view others negatively, compared
      with both control groups.

PMID- 11531204
TI  - Abusive relationships in families of women with borderline personality disorder,
      anorexia nervosa and a control group.
AB  - In a group of intact families, we examined the rates and parameters of verbal,
      physical, and sexual abuse in 35 women with borderline personality disorder
      (BPD), 34 women with anorexia nervosa (AN), and 33 women without a clinical
      history (NC); their experience of multiple abuse and its correlation with their
      SCL-90-R scores; and their reports of abuse of their siblings. Corroboration of
      abuse was obtained from some parents in each group. Women with BPD suffered more
      intrafamilial verbal and physical abuse. Whereas AN and NC women experienced
      relatively rare single events of extrafamilial sexual abuse at an older age,
      those with BPD suffered repeated intrafamilial sexual abuse at a younger age and
      also suffered more multiple abuse. All multiply abused women had more
      psychopathology. Siblings were reported abused in the same proportions as
      subjects; many parents of BPDs corroborated their daughters' reports of all three
      forms of abuse.

PMID- 11531205
TI  - Gender differences in violence exposure and violence risk among adolescent
      inpatients.
AB  - Gender-specific rates of violence exposure and violence perpetration among
      psychiatrically ill adolescents has received little scientific attention. We
      examined 130 adolescent inpatients and found no difference between male and
      female subjects with respect to self-reported violence potential or actual
      violence perpetration. Female inpatients, however, were significantly more often
      victims of sexual assault, and male inpatients were significantly more often
      victims of physical assault. For male inpatients, a history of violence
      perpetration in one area was closely linked with a history of violence
      victimization in the same area. Alternatively, patterns of victimization and
      perpetration among female inpatients were less predictable and had crossover to
      victimization and perpetration experiences in other areas. Correlational analyses
      revealed that violence risk was associated with a broad range of internalizing
      and externalizing psychopathology. Significant associations with hopelessness,
      suicidality, and childhood trauma differentiated the violence risk of male and
      female inpatients. We propose a hypothesis for understanding these differences
      and conclude that although psychiatrically ill adolescent male and female
      patients may commonly fall victim to differing forms of violence, both genders
      are at equal risk for actual violence perpetration.

PMID- 11531206
TI  - Risk factors for posttrauma reactions in police officers: a longitudinal study.
AB  - This prospective, longitudinal study investigated risk factors in the development
      of psychological ill health and posttraumatic stress symptoms in a sample of 223
      junior police officers. Participants were assessed using a self-report
      methodology during training and again 12 months later on a range of personality,
      trauma exposure, and symptom measures. Risk factors for general psychological ill
      health at phase 2 of the research were found to comprise mostly stable,
      preexisting characteristics such as personality style, gender, and trait
      dissociation. Conversely, specific traumatic stress symptoms were more heavily
      influenced by experiences in the intervening 12 months, such as severity of
      incident exposure and peritraumatic dissociation. The implications for
      differential intervention are discussed.

PMID- 11531207
TI  - Posttraumatic stress disorder and major depressive disorder: investigating the
      role of overlapping symptoms in diagnostic comorbidity.
AB  - Studies of posttraumatic stress disorder (PTSD) have found high levels of
      comorbid major depressive disorder (MDD). One reason suggested for the
      comorbidity is the symptom overlap (contaminated symptoms) between the disorders.
      The present study investigated the contribution of contaminated symptoms
      (anhedonia, concentration, and sleep problems) to the comorbidity of PTSD and
      MDD. PTSD symptoms were subdivided into two groups: the contaminated symptoms and
      the 14 unique symptoms. It was speculated that if the contaminated symptoms are
      responsible for the comorbidity, then they will show less specificity than the
      unique symptoms, will be less highly correlated with a PTSD symptom total count,
      and be more frequently endorsed in PTSD patients with than without MDD. These
      hypotheses were tested in a sample (N = 1300) of psychiatric outpatients, 260 of
      whom had lifetime PTSD. None of the hypotheses were supported, thereby suggesting
      that the comorbidity between PTSD and MDD is not an artifact of symptom overlap.

PMID- 11531208
TI  - Loss of time-organized sympathetic skin responses in acute psychosis.
AB  - The aim of this study was to differentiate the response pattern characteristics
      of sympathetic skin responses (SSR) between unmedicated first psychotic subjects
      and healthy controls. We recorded SSR to novel auditory stimuli in 13 psychotic
      subjects and in 19 controls. There was no constant delay between a sudden change
      in the acoustic surroundings and SSR in psychotic subjects, whereas regularly
      this delay was 1.3 to 1.8 seconds in controls. The validity of the test was
      evaluated by blind rating responses to two categories. The lack of a regular time
      delay between a novel auditory stimulus and SSR suggests a timing disturbance in
      the neural networks regulating the autonomic nervous system responses in acute
      psychosis. Our finding and method may have future implications in evaluation of
      subtle autonomic nervous system alterations related, e.g., to drug effects.

PMID- 11531209
TI  - Nightmares of refugees from Kurdistan.

PMID- 11531210
TI  - Dream recall, nightmare frequency, and nocturnal panic attacks in patients with
      panic disorder.

PMID- 11531211
TI  - Further evidence for delayed alternation deficits in obsessive-compulsive
      disorder.

PMID- 11531212
TI  - Hepatic de novo lipogenesis after liver transplantation.
AB  - BACKGROUND: The liver can synthesize fatty acids from carbohydrate (de novo
      lipogenesis [DNL]). We hypothesized that stimulation of this process may be
      involved in the development of obesity and dyslipidemia, 2 conditions frequently
      encountered after liver transplantation. METHODS: Hepatic fractional DNL and
      glucose metabolism were measured in 2 groups of 5 patients (age 36.8 +/- [SD]
      14.9 years, BMI 26.3+/-5.3 kg/M2) 1 to 5 years after liver transplantation and 8
      healthy subjects (age 28.1+/-5.3 years, BMI 27.2+/-4.5 kg/M2). Subjects were
      studied while receiving an isoenergetic nutrition (based on 1.1 x their basal
      energy expenditure) as hourly oral liquid formula during 10 hours. Their hepatic
      DNL was measured by infusing 1-13C acetate and measuring tracer incorporation in
      VLDL-palmitate. Their glucose metabolism was assessed by means of 6,6-2H2 glucose
      and indirect calorimetry. RESULTS: Two liver transplant recipients and 4 healthy
      subjects were obese, as defined by a BMI > 27 kg/M2. Fractional hepatic DNL was
      not different in the 2 groups of subjects: liver transplant recipients 3.1+/-1.7%
      vs 3.2+/-2.1% in healthy subjects. In both groups, DNL increased in proportion to
      BMI. When both groups were analyzed together, BMI was positively correlated with
      DNL (DNL = 0.28 x BMI - 4.28, r2 = .445, p < .05). Whole body glucose turnover
      was 15.0+/-4.4 micromol/kg per minute in liver transplant recipients and 15.8+/
      4.1 micromol/kg per minute in healthy subjects (NS). Net carbohydrate oxidation
      tended to be lower in liver transplant recipients (8.1+/-2.6 micromol/kg per
      minute) than in healthy subjects (10.4+/-2.4 micromol/kg per minute; NS). Net
      nonoxidative glucose disposal (4.0+/-2.7 in liver transplant recipients vs 1.9+/
      1.8 in healthy subjects, NS) and energy expenditure (0.065+/-0.01 vs 0.065+/-0.01
      kJ/kg per minute) were similar in both groups. CONCLUSIONS: These results
      indicate that fractional hepatic DNL is not altered by liver transplantation
      during near continuous nutrition. The disposal of orally administered
      carbohydrate is also essentially unchanged. This strongly argues against a role
      of hepatic DNL in the pathogenesis of obesity and dyslipidemia after liver
      transplantation.

PMID- 11531213
TI  - Parenteral structured triglyceride emulsion improves nitrogen balance and is
      cleared faster from the blood in moderately catabolic patients.
AB  - BACKGROUND: Most postoperative patients lose net protein mass, which reflects
      loss of muscle tissue and organ function. Perioperative parenteral nutrition may
      reduce the loss of protein, but in general, with conventional lipid emulsions a
      waste of protein still remains. METHODS: We compared the effects on nitrogen
      balance of an emulsion containing structured triglycerides, a new type of
      synthesized triglycerides, with an emulsion of a physical mixture of medium- and
      long-chain triglycerides as part of parenteral feeding in moderately catabolic
      patients. The first 5 days after placement of an aortic prosthesis patients
      received total parenteral nutrition (TPN) providing 0.2 g of nitrogen per kg body
      weight per day; energy requirement was calculated using Harris and Benedict's
      equation, adding 300 kcal per day for activity. Twelve patients were treated with
      the structured triglyceride emulsion and 13 patients with the emulsion of the
      physical mixture of medium- and long-chain triglycerides. The design was a
      randomized, double-blind parallel study. RESULTS: In the patients who completed
      the study, the mean cumulative nitrogen balance over the first 5 postoperative
      days was -8+/-2 g in 10 patients on the structured triglyceride emulsion and 
      21+/-4 g in 9 patients on the emulsion of the physical mixture of medium- and
      long-chain triglycerides; the mean difference was 13 g of nitrogen (95%
      confidence interval 4 to 22, p = .015) in favor of the structured triglyceride
      emulsion. On the first postoperative day serum triglyceride and plasma medium
      chain free fatty acid levels increased less during infusion of the structured
      triglyceride emulsion than with the physical mixture emulsion. CONCLUSIONS: The
      parenteral structured triglyceride emulsion improves the nitrogen balance and is
      cleared faster from the blood, compared with the emulsion of the physical mixture
      of medium- and long-chain triglycerides, in moderately catabolic patients.

PMID- 11531214
TI  - Parenteral structured triglyceride emulsion improves nitrogen balance and is
      cleared faster from the blood in moderately catabolic patients.

PMID- 11531215
TI  - Luminal nutrients exacerbate intestinal hypoxia in the hypoperfused jejunum.
AB  - BACKGROUND: Provision of enteral nutrients shortly after traumatic injury has
      become the preferred method of nutrition support provided to patients. However,
      traumatic shock results in splanchnic hypoperfusion, which may cause persistent
      intestinal hypoxia. This study tested the hypothesis that delivery of enteral
      nutrients to the hypoperfused jejunum increases oxidative demand beyond that
      available, thereby exacerbating intestinal hypoxia. METHODS: Wistar-Furth rats
      (186+/-4 g; n = 24) were randomized to receive intestinal hypoxia (superior
      mesenteric artery occlusion) or serve as normoxic controls (sham laparotomy).
      Within the jejunum of each rat, 4 6-cm loops were randomized to receive luminal
      perfusions with 1 of 4 substrates: mannitol (an osmotic control); glucose
      (undergoes active transport via the sodium-glucose co-transporter [SGLT-1] and is
      metabolized); 3-o-methylglucose (3-o-mg; uses SGLT-1 but is not metabolized); or
      fructose (does not use SGLT-1 but is metabolized). After in situ perfusions,
      jejunal tissue was removed for analysis of nutrient transport and barrier
      function in modified Ussing chambers. Tissue homogenate was used to determine
      concentration of ATP, lactate, pyruvate, and protein. Also, jejunal tissue was
      stained with hematoxylin and eosin for qualitative analysis of ischemia and
      necrosis. RESULTS: Transmural resistance was lower (p < .001) in the hypoxia
      groups, irrespective of substrate, indicating increased mucosal permeability.
      When compared with the normoxic controls, glucose transport was impaired (p <
      .001) in the hypoxic groups; however, glutamine transport was unaffected. The
      degree of intestinal hypoxia, assessed by jejunal lactate concentration, was
      higher (p < .001) in the glucose and fructose groups, than the control mannitol
      and 3-o-mg groups. CONCLUSIONS: The observation that 3-o-mg did not differ from
      the mannitol control indicates that SGLT-1 activation alone does not exacerbate
      hypoxia. Rather, these results indicate that provision of metabolizable nutrients
      to the hypoperfused intestine exacerbate hypoxia and potentially lead to
      intestinal ischemia. Although early enteral nutrition is an important
      intervention after trauma, care must be taken to ensure intestinal perfusion is
      adequate to allow for nutrient metabolism and prevent further compromise.

PMID- 11531216
TI  - Effects of age, feeding regimen, and glucocorticoids on catecholamine and
      cortisol excretion in preterm infants.
AB  - BACKGROUND: The sympathoadrenal system is important in maintaining normal
      physiologic functioning in infants and increased output also can reflect stress.
      We sought to determine the effects of age, feeding regimen, and glucocorticoids
      on catecholamine and cortisol excretion in preterm infants and to assess whether
      a particular strategy of feeding enhanced sympathoadrenal development or was
      stressful. METHODS: Preterm infants (26-30 wk gestation; n = 171) were assigned
      randomly to begin trophic feedings from day 4 through 14 (trophic group) or to
      start feedings at day 15 (standard group) with feedings administered either by
      bolus every 3 hours (bolus) or continuously over 24 hours (continuous). At 10,
      28, 40, 50, and 60 days of age, urine was collected continuously for 6 hours for
      measurement of catecholamines (norepinephrine, epinephrine, dopamine), cortisol,
      and creatinine. Data were available for 98 infants. RESULTS: Norepinephrine
      excretion increased with postnatal age. The increase with age was significantly
      greater in the trophic group compared with that in the standard group.
      Epinephrine excretion did not change with age, and there were no differences
      between trophic and standard groups. Dopamine excretion increased with age but
      was similar between trophic and standard groups (borderline significantly greater
      in the trophic group). Cortisol excretion increased with age and also was similar
      between trophic and standard groups. There was no effect on catecholamine or
      cortisol excretion of bolus vs continuous feedings, antenatal or postnatal
      corticosteroids, gestational age at birth, age at which full feedings were
      attained, or use of human milk compared with preterm formula. CONCLUSIONS: The
      greatest determinant of catecholamine and cortisol excretion is postnatal age.
      Feeding method, type of feeding, and glucocorticoid administration in the amounts
      customarily used have little significant effect on catecholamine or cortisol
      excretion. The apparent link between early feeding and norepinephrine (and
      possibly dopamine) excretion warrants further investigation.

PMID- 11531217
TI  - Choline deficiency causes reversible hepatic abnormalities in patients receiving
      parenteral nutrition: proof of a human choline requirement: a placebo-controlled
      trial.
AB  - BACKGROUND: Previous studies have shown that plasma free choline concentrations
      are significantly decreased in many long-term home total parenteral nutrition
      (TPN) patients. Furthermore, low choline status has been associated with both
      hepatic morphologic and hepatic aminotransferase abnormalities. A preliminary
      pilot study suggested choline-supplemented TPN may be useful in reversal of these
      hepatic abnormalities. METHODS: Fifteen patients (10 M, 5 F) who had required TPN
      for > or =80% of their nutritional needs were randomized to receive their usual
      TPN (n = 8), or TPN to which 2 g choline chloride had been added (n = 7) for 24
      weeks. Baseline demographic data were similar between groups. Patients had CT
      scans of the liver and spleen, and blood for plasma free and phospholipid-bound
      choline, alanine aminotransferase (ALT), aspartate aminotransferase (AST),
      alkaline phosphatase, gamma glutamyl transferase (GGT), bilirubin, serum lipids,
      complete blood count (CBC), and chemistry profile obtained at baseline, and weeks
      2, 4, 6, 12, 16, 20, 24, and 34. CT scans were analyzed for Hounsfield unit (HU)
      densities. RESULTS: There were no significant differences in any measured
      parameters after 2 weeks. However, at 4 weeks, a significant difference in liver
      HU between groups was observed (13.3+/-5.0 HU [choline] vs 5.8+/-5.2 HU
      [placebo], p = .04). This significant trend continued through week 24. Recurrent
      hepatic steatosis and decreased HU were observed at week 34, 10 weeks after
      choline supplementation had been discontinued. A significant increase in the
      liver-spleen differential HU was also observed in the choline group (10.6+/-6.2
      HU [choline] vs 1.3+/-3.3 HU [placebo], p = .01). Serum ALT decreased
      significantly (p = .01 to .05) in the choline group vs placebo at weeks 6,12, 20,
      and 24. Serum AST was significantly decreased in the choline group by week 24 (p
      = .02). The serum alkaline phosphatase was significantly reduced in the choline
      group at weeks 2, 12, 20, 24, and 34 (p = .02 to 0.07). Total bilirubin was
      normal in these patients and remained unchanged during the study. Serum GGT
      tended to decrease more in the choline group, but the greater decrease was not
      statistically significant. CONCLUSIONS: Choline deficiency is a significant
      contributor to the development of TPN-associated liver disease. The data suggest
      choline is a required nutrient for long-term home TPN patients.

PMID- 11531218
TI  - Effects of glutamine-supplemented total parenteral nutrition on cytokine
      production and T cell population in septic rats.
AB  - BACKGROUND: This study was designed to investigate the effects of total
      parenteral nutrition (TPN) enriched with glutamine (GLN) on in vivo cytokine
      production and cellular immune response in early and late septic stages of rats.
      METHODS: Male Wistar rats were divided into 2 experimental groups and received
      TPN solution at an energy level of 270 kcal/kg body weight. The TPN solutions
      were isonitrogenous and identical in nutrients composition except for differences
      in amino acid content. One group received 2% GLN, whereas the other group
      received glycine (Gly) instead. TPN was maintained for 5 or 6 days according to
      the sacrifice schedule of the rats. On day 5, sepsis was induced by cecal
      ligation and puncture (CLP). Respective groups of rats were sacrificed 2, 4, 6,
      and 24 hours after CLP. RESULTS: Sepsis resulted in a negative nitrogen balance
      in both groups, and nitrogen loss was significantly lower in the GLN than the Gly
      group. Interleukin (IL)-2 and interferon (IFN)-gamma in most of the samples
      collected at various time points were not detectable in plasma or peritoneal
      lavage fluid. No differences in plasma IL-6 and TNF-alpha concentrations were
      observed between the GLN and Gly groups. Also, there were no significant
      differences in IL-1beta, IL-6, and TNF-alpha concentrations in peritoneal lavage
      fluid between the 2 groups at various time points. The CD4+/CD8+ ratio was
      significantly higher in the GLN group than in the Gly group only at 4 hours after
      CLP, and no difference was observed at 24 hours after CLP. CONCLUSIONS: TPN
      preinfused with a GLN-supplemented solution had a beneficial effect in
      ameliorating the extent of negative nitrogen balance in septic rats. However,
      parenterally administered GLN did not reduce the production of inflammatory
      mediators systemically or at the site of injury, and the influence on enhancing
      cellular immunity was not obvious.

PMID- 11531219
TI  - The role of eicosanoids in the process of adaptation following massive bowel
      resection in the rat.
AB  - BACKGROUND: Long chain polyunsaturated fatty acids (LCPUFAs) such as arachidonic
      acid (AA) and eicosapentaenoic acid (EPA) stimulate intestinal adaptation.
      Prostaglandins also enhance intestinal adaptation. The purpose of this study was
      to determine by which eicosanoid pathway dietary arachidonic acid enhances
      intestinal adaptation. Cyclo-oxygenase or lipoxygenase were selectively inhibited
      to determine whether either of them enhanced or inhibited adaptation. METHODS:
      Sixty Sprague-Dawley rats were divided into 2 groups, one receiving an 80% small
      bowel resection and the other receiving a sham operation. Rats were further
      divided into groups receiving either a placebo, a general lipoxygenase inhibitor
      (nordihydroguaiaretic acid [NDGA] at 40 mg/kg per day), or a cyclo-oxygenase-2
      inhibitor (Etodolac at 3 mg/kg per day). Rats were pair-fed a diet containing 30%
      kcal from fat, primarily consisting of AA. RESULTS: After 14 days, mucosal mass,
      protein, DNA, and disaccharidase activity were measured in the remaining small
      intestine. There was a significant decrease in ileal mucosal mass in rats
      receiving Etodolac and a significant increase in mucosal mass in the duodenum in
      rats receiving NDGA (both p < .001). Mucosal DNA, protein, and disaccharidase
      data showed similar trends. CONCLUSIONS: These findings suggest that after small
      bowel resection, dietary arachidonic acid may facilitate the adaptation process
      by acting as a substrate for the synthesis of prostaglandins, and not through the
      derivatives of lipoxygenase such as leukotrienes or thromboxanes.

PMID- 11531220
TI  - Metastasis of head and neck carcinoma to the site of percutaneous endoscopic
      gastrostomy: case report and literature review.
AB  - BACKGROUND: Patients with head and neck cancer often need a percutaneous
      endoscopic gastrostomy to provide adequate nutrition because of inability to
      swallow after tumor radiation therapy. However, metastasis of the original tumor
      to the gastrostomy exit site may occur. METHODS: We describe the case of a 61
      year-old man with stage III (T2 N1) squamous cell carcinoma of the tongue in whom
      a PEG tube was placed to circumvent anticipated difficulties in swallowing after
      radiation therapy. We also compare this case with similar cases in the
      literature. RESULTS: Soreness and erythema near the gastrostomy site reported by
      the patient were diagnosed as cellulitis, and two courses of antibiotic treatment
      were prescribed. However, a biopsy showed that the original squamous cell
      carcinoma had metastasized to the gastrostomy exit site. The "pull" method of
      tube placement had been used in this patient and in all 19 cases of metastasis
      reported in the literature. CONCLUSIONS: Metastatic cancer should be considered
      in patients with head and neck cancer who have unexplained skin changes at the
      gastrostomy site. Our experience with this case and review of the literature
      indicate that, in patients with head and neck cancer, "pull" procedures for
      placement of gastrostomy tubes may induce metastasis by direct implantation of
      tumor cells because of contact between the gastrostomy tube and tumor cells.
      Methods of tube insertion that avoid such contact are preferred.

PMID- 11531221
TI  - Arginine deficiency-induced hyperammonemia in a home total parenteral nutrition
      dependent patient: a case report.
AB  - BACKGROUND: Patients with short bowel syndrome and renal dysfunction with TPN
      dependence are at high risk for developing hyperammonemia if the TPN does not
      contain sufficient quantities of arginine. Providing proper nutrition support is
      essential in the management of these patients. METHODS: We report on a patient
      with short bowel syndrome, TPN dependence, and normal renal function who
      developed hyperammonemic encephalopathy due to inadvertent lack of arginine in
      his TPN. RESULTS: The patient was successfully treated with hemodialysis and an
      IV arginine infusion to resolve the hyperammonemia. His home TPN was also
      adjusted such that arginine was added to his subsequent solutions. CONCLUSIONS:
      Our patient underscores the importance of adequate and sustained arginine
      supplementation to avoid hyperammonemia in TPN dependent patients with short
      bowel syndrome.

PMID- 11531222
TI  - Finite mixture distribution models of simple discrimination learning.
AB  - Through the application of finite mixture distribution models, we investigated
      the existence of distinct modes of behavior in learning a simple discrimination.
      The data were obtained in a repeated measures study in which subjects aged 6 to
      10 years carried out a simple discrimination learning task. In contrast to
      distribution models of exclusively rational learners or exclusively incremental
      learners, a mixture distribution model of rational learners and slow learners was
      found to fit the data of all measurement occasions and all age groups. Hence, the
      finite mixture distribution analysis provides strong support for the existence of
      distinct modes of learning behavior. The results of a second experiment support
      this conclusion by crossvalidation of the models that fit the data of the first
      experiment. The effect of verbally labeling the values on the relevant stimulus
      dimension and the consistency of behavior over measurement occasions are related
      to the mixture model estimates.

PMID- 11531223
TI  - Search and selection processes in implicit and explicit word-stem completion
      performance in young, middle-aged, and older adults.
AB  - In the present investigation, we sought to (1) replicate previous reports of
      impaired word-stem completion (WSC) priming and cued recall performance in older
      adults, (2) gain a better understanding of the differential roles of search and
      selection processes in implicit and explicit WSC, and (3) determine the
      particular aspects of WSC performance that are influenced by age. Experiment 1
      demonstrated that older adults primed and recalled fewer items on a WSC task than
      middle-aged adults did, who in turn primed and recalled fewer items than young
      adults did. A series of item analyses indicated that choice of a stem completion
      is influenced by two independent sources of information: the familiarity of the
      completion reflected by word frequency and the cue-specific match between the
      stem and the completion word based on the common pronunciation of the stem.
      Experiment 2 demonstrated that older adults utilized cue-specific matching to the
      same degree as young and middle-aged adults. However, the impact of target
      familiarity changed across the lifespan. Older adults produced and recalled high
      frequency targets as well as young adults but produced and recalled fewer low
      frequency targets than did young participants. The results are consistent with
      the view that older adults rely on familiarity to a greater degree than do young
      adults.

PMID- 11531224
TI  - Parallel effects of aging and time pressure on memory for source: evidence from
      the spacing effect.
AB  - Two experiments address the degree to which item memory-the ability to remember
      that a word has been presented-is dissociable from source memory, or the ability
      to remember the context of that word's presentation. Spacing (as opposed to
      massing) an item's two presentations leads young adults to endorse that item more
      often when they are instructed to recognize it and to reject it more often when
      they are instructed to exclude it. Old adults also enjoy beneficial effects of
      spacing when the item is to be recognized, but suffer detrimental effects of the
      spacing manipulation when the item is to be rejected: They falsely endorse the
      spaced to-be-rejected items more than the massed ones. This dissociation also
      obtains with young subjects under conditions of increased time pressure: Under
      normal decision conditions, the ability to endorse to-be-recognized items and to
      reject to-be-rejected items increases with spacing; under speeded conditions, the
      ability to reject the latter items decreases with spacing. The results support
      the notion that source memory is selectively impaired in the elderly and that it
      is difficult to access mnemonic information about source under time pressure.

PMID- 11531225
TI  - Perceptual and conceptual sources of priming on a word generation task.
AB  - Repetition of any number of cognitive processes can facilitate subsequent
      performance (i.e., repetition priming). In this study, we explored several
      candidate mechanisms that could account for repetition priming on a word
      generation task. In Experiment 1, we examined whether repetition of semantic
      processing is necessary for priming on this task. In Experiment 2, we examined
      whether repetition of semantic processing is sufficient for priming on this task.
      In both experiments, we additionally examined the effect of changing the specific
      nature of the semantic retrieval task (i.e., from visual to functional, and vice
      versa) on performance. The results from these experiments indicated that
      repetition of semantic processing is both necessary and sufficient to produce a
      facilitation effect on the word generation task. However, semantic processing of
      the same attribute does not need to be repeated for facilitation effects to
      occur. Implications of these findings for theories of the representation and
      retrieval of semantic knowledge are discussed.

PMID- 11531226
TI  - Imagination inflation: a statistical artifact of regression toward the mean.
AB  - In the imagination inflation procedure of Garry, Manning, Loftus, and Sherman
      (1996), subjects rated a list of events in terms of how likely each was to have
      occurred in their childhood. Two weeks later, some of the events were imagined;
      control events were not. The subjects then rated the likelihood of occurrence for
      each event a second time. Garry et al. (1996) reported that the act of imagining
      the target events led to increased ratings of likelihood. This finding has been
      interpreted as indicating that false events can be suggestively planted in memory
      by simply having people imagine them. The present study tests and confirms the
      hypothesis that the results that have been attributed to imagination inflation
      are simply a statistical artifact of regression toward the mean. The experiment
      of Garry et al. (1996) was reproduced (with some procedural changes), using
      younger and older adults. The results of Garry et al. (1996) were replicated;
      likelihood ratings for events initially rated low in likelihood did increase from
      Time 1 to Time 2. However, ratings for events initially rated high in likelihood
      decreased under the same conditions, and these results were consistent with the
      imagined target events, the target events not imagined, and the nontarget events.

PMID- 11531227
TI  - Analogy use in naturalistic settings: the influence of audience, emotion, and
      goals.
AB  - The ways in which analogy was used in a nonexperimental environment-politics-was
      investigated. We used the framework developed in analogy research to analyze the
      selection of analogical sources in political discourse. We took all the analogies
      reported in newspapers during the final week of a referendum campaign in Canada
      and analyzed the features of the different analogies used. We identified 234
      analogies and analyzed the range over which analogies were used, semantic
      categories of analogies, goals of the analogizer, and emotional connotation of
      the analogies. Our results reveal that analogy was frequently used, that over two
      thirds of the analogical sources were nonpolitical, and that many of the sources
      had strong emotional connotations. Furthermore, the goal of the analogizer
      influenced the selection of sources. We conclude that characteristics of the
      audience and emotionality of the source analog are important features in the
      selection of source analogs.

PMID- 11531228
TI  - Suppression of valid inferences and knowledge structures: the curious effect of
      producing alternative antecedents on reasoning with causal conditionals.
AB  - These studies looked at the difficulty that reasoners have in accepting
      conditional ("If P then Q") major premises that are not necessarily true
      empirically, as a basis for deductive reasoning. Preliminary results have shown
      that when reasoners are asked to produce possible alternate antecedents to the
      major premise ("If A then Q"), they paradoxically tend to deny the modus ponens
      (MP) inference ("If P is true, then Q is true"). Three studies further explored
      these results. The first study gave university students paper-and-pencil tests in
      which instructions to "suppose that the major premise is true" was followed by a
      request to determine the next number in a sequence, to retrieve information
      unrelated to the premises, or to retrieve a possible case of "If A then Q."
      Relative to a control group, reasoners asked to produce an alternative antecedent
      showed a significant tendency to deny the MP inference, whereas no such tendency
      was observed for the two other tasks used. A second study compared performance on
      a condition in which reasoners were asked to produce an alternative antecedent
      with that when they were given an explicit alternative. Premises used in this
      study were such that the latter alternative antecedent was also spontaneously
      produced by over 70% of reasoners. Results showed that the tendency to refuse the
      MP premise could not be accounted for by the specific nature of the alternative
      produced. A third study found that the tendency to refuse the MP inference after
      producing an alternative antecedent was affected by the number of "disabling
      conditions" (i.e., conditions that allow "P to be true" and "Q to be false")
      available for the major premise. These results are interpreted as being
      consistent with a model that supposes that logical reasoning requires selective
      inhibition of real-world knowledge.

PMID- 11531229
TI  - A dissociation between object manipulation spatial ability and spatial
      orientation ability.
AB  - We developed psychometric tests of spatial orientation ability, in which people
      are shown a two-dimensional array of objects, imagine taking a perspective within
      the array, and indicate the direction to a target object from this perspective.
      Patterns of errors on these tests were consistent with experimental studies of
      perspective taking. Characteristic errors and verbal protocols supported the
      validity of the perspective-taking tests, suggesting that people encoded the
      objects in the display with respect to a body-centered coordinate system when the
      imagined perspective was more than 90 degrees different from the orientation of
      the display. By comparing alternative models in a confirmatory factor analysis,
      we found that the ability to mentally rotate and manipulate an imagined object
      (as measured by tests of spatial visualization and spatial relations) and the
      ability to reorient the imagined self (as measured by the perspective-taking
      tests) are separable spatial abilities.

PMID- 11531230
TI  - Let's swap: early understanding of social exchange by British and Nepali
      children.
AB  - Recent research with adults has suggested that they readily understand
      conditional rules that include a deontic or prescriptive element. The possibility
      that young children might also understand such conditional rules when they are
      embedded in the context of an exchange agreement was explored in three studies.
      Children 3-7 years of age listened to stories in which two protagonists agreed to
      an exchange of mutual benefit. Children tested both in Britain and Nepal were
      accurate in identifying (1) when either protagonist had reneged on the agreement
      and (2) when both protagonists had kept the agreement. The findings indicate that
      young children are sensitive to the obligations that stem from an exchange
      agreement even if it is made between equals rather than imposed by adult
      authority.

PMID- 11531232
TI  - Phonological similarity in working memory.
AB  - That phonologically similar words in a short-term memory test are more difficult
      to recall than phonologically dissimilar words is a well-known phenomenon. This
      effect is the phonological similarity decrement. In the present study, we
      examined whether this phonological similarity decrement is present when
      additional semantic information is available, as in a reading span test, as
      compared with a standard presentation, or in the context of an operation span
      test. The results revealed a phonological similarity facilitation. Phonologically
      similar words were remembered better than phonologically dissimilar words.

PMID- 11531231
TI  - Prelexical phonological coding of visual words in Dutch: automatic after all.
AB  - This paper addresses a previous claim (Brysbaert & Praet, 1992) that the use of
      prelexical phonology in visual word recognition is optional in the Dutch
      language. One backward masking experiment and two masked priming experiments are
      reported. The experimental task was perceptual identification. Pseudohomophones,
      graphemic controls, and unrelated controls of the target words were used as masks
      or primes. The main findings were (1) unlike previous claims, the pseudohomophone
      effect is not strategic in Dutch, but (2) the effect is more clearly obtained
      with the masked priming procedure than with the backward masking procedure.

PMID- 11531233
TI  - Early action to reduce greenhouse gas emissions before the commitment period of
      the Kyoto protocol: advantages and disadvantages.
AB  - Current "business as usual" projections suggest greenhouse gas emissions from
      industrialized nations will grow substantially over the next decade. However, if
      it comes into force, the Kyoto Protocol will require industrialized nations to
      reduce emissions to an average of 5% below 1990 levels in the 2008-2012 period.
      Taking early action to close this gap has a number of advantages. It reduces the
      risks of passing thresholds that trigger climate change "surprises." Early action
      also increases future generations' ability to choose greater levels of climate
      protection, and it leads to faster reductions of other pollutants. From an
      economic sense, early action is important because it allows shifts to less carbon
      intensive technologies during the course of normal capital stock turnover.
      Moreover, many options for emission reduction have negative costs, and thus are
      economically worthwhile, because of paybacks in energy costs, healthcare costs,
      and other benefits. Finally, early emission reductions enhance the probability of
      successful ratification and lower the risk of noncompliance with the protocol. We
      discuss policy approaches for the period prior to 2008. Disadvantages of the
      current proposals for Credit for Early Action are the possibility of adverse
      selection due to problematic baseline calculation methods as well as the
      distributionary impacts of allocating a part of the emissions budget already
      before 2008. One simple policy without drawbacks is the so-called baseline
      protection, which removes the disincentive to early action due to the expectation
      that businesses may, in the future, receive emission rights in proportion to past
      emissions. It is particularly important to adopt policies that shift investment
      in long-lived capital stock towards less carbon-intensive technologies and to
      encourage innovation and technology development that will reduce future
      compliance costs.

PMID- 11531234
TI  - Developing a spatial framework of common ecological regions for the conterminous
      United States.
AB  - In 1996, nine federal agencies with mandates to inventory and manage the nation's
      land, water, and biological resources signed a memorandum of understanding
      entitled "Developing a Spatial Framework of Ecological Units of The United
      States." This spatial framework is the basis for interagency coordination and
      collaboration in the development of ecosystem management strategies. One of the
      objectives in this memorandum is the development of a map of common ecological
      regions for the conterminous United States. The regions defined in the spatial
      framework will be areas within which biotic, abiotic, terrestrial, and aquatic
      capacities and potentials are similar. The agencies agreed to begin by exploring
      areas of agreement and disagreement in three federal natural-resource spatial
      frameworks--Major Land Resource Areas of the US Department of Agriculture (USDA)
      Natural Resources Conservation Service, National Hierarchy of Ecological Units of
      the USDA Forest Service, and Level III Ecoregions of the US Environmental
      Protection Agency. The explicit intention is that the framework will foster an
      ecological understanding of the landscape, rather than an understanding based on
      a single resource, single discipline, or single agency perspective. This paper
      describes the origin, capabilities, and limitations of three major federal agency
      frameworks and suggests why a common ecological framework is desirable. The
      scientific and programmatic benefits of common ecological regions are described,
      and a proposed process for development of the common framework is presented.

PMID- 11531235
TI  - A landscape analysis of cougar distribution and abundance in Montana, USA.
AB  - Recent growth in the distribution and abundance of cougars (Puma concolor)
      throughout western North America has created opportunities, challenges, and
      problems for wildlife managers and raises questions about what factors affect
      cougar populations. We present an analysis of factors thought to affect cougar
      distribution and abundance across the broad geographical scales on which most
      population management decisions are made. Our objectives were to: (1) identify
      and evaluate landscape parameters that can be used to predict the capability of
      habitats to support cougars, and (2) evaluate factors that may account for the
      recent expansion in cougar numbers. Habitat values based on terrain ruggedness
      and forested cover explained 73% of the variation in a cougar abundance index.
      Indices of cougar abundance also were spatially and temporally correlated with
      ungulate abundance. An increase in the number and total biomass of ungulate prey
      species is hypothesized to account for recent increases in cougars. Cougar
      populations in Montana are coping with land development by humans when other
      components of habitat and prey populations are sufficient. Our analysis provides
      a better understanding of what may have influenced recent growth in cougar
      distribution and abundance in Montana and, when combined with insights about
      stakeholder acceptance capacity, offers a basis for cougar management at broad
      scales. Long-term conservation of cougars necessitates a better understanding of
      ecosystem functions that affect prey distribution and abundance, more accurate
      estimates of cougar populations, and management abilities to integrate these
      components with human values.

PMID- 11531236
TI  - Land-use dynamics in a southern Illinois (USA) watershed.
AB  - The Cache River of southernmost Illinois is used as a case study for developing
      and demonstrating an approach to quantitatively link (1) national agricultural
      policy and global agricultural markets, (2) landowner's decisions on land use,
      (3) spatial patterns of land use at a watershed scale, and (4) hydrologic
      impacts, thus providing a basis to predict, under a certain set of circumstances,
      the environmental consequences of economic and political decisions made at larger
      spatial scales. The heart of the analysis is an estimation, using logistic
      regression, of the affect of crop prices and Conservation Reserve Program (CRP)
      rental rates on farmland owner's decisions whether to reenroll in the CRP or
      return to crop production. This analysis shows that reasonable ranges for crop
      prices (80%-150% of 1985-1995 values) and CRP rental rates (0-125% of 1985-1995
      rates) result in a range of 3%-92% of CRP lands being returned to crop
      production, with crop prices having a slightly greater effect than CRP rental
      rates. Four crop price/CRP rental rate scenarios are used to display resulting
      land-use patterns, and their effect on sediment loads, a critical environmental
      quality parameter in this case, using the agricultural non point source (AGNPS)
      model. These scenarios demonstrate the importance of spatial pattern of land uses
      on hydrological and ecological processes within watersheds. The approach
      developed can be adapted for use by local governments and watershed associations
      whose goals are to improve watershed resources and environmental quality.

PMID- 11531237
TI  - A geomorphologist's criticism of the engineering approach to channelization of
      gravel-bed rivers: case study of the Raba River, Polish Carpathians.
AB  - River engineers use sediment transport formulas to design regulated channels in
      which the river's ability to transport bedload would remain in equilibrium with
      the delivery of materials from upstream. In gravel-bed rivers, a number of
      factors distort the simple relationship between particle size and hydraulic
      parameters at the threshold of sediment motion, inherent in the formulas. This
      may lead to significant errors in predicting the bedload transport rates in such
      streams and hence to instability of their regulated channels. The failure to
      recognize a nonstationary river regime may also result in unsuccessful
      channelization. Rapid channel incision has followed channelization of the main
      rivers of the Polish Carpathians in the 20th century. A case study of the Raba
      River shows that incision has resulted from the increase in stream power caused
      by channelization and the simultaneous reduction in sediment supply due to
      variations in basin management and a change in flood hydrographs. Calculations of
      bedload transport in the river by the Meyer-Peter and Muller formula are shown to
      have resulted in unrealistic estimates, perhaps because the different degree of
      bed armoring in particular cross-sections was neglected. It would have been
      possible to avoid improper channelization if the decreasing trend in sediment
      load of the Carpathian rivers had been recognized on the basis of
      geomorphological and sedimentological studies. Allowing the rivers to increase
      their sinuosity, wherever possible without an erosional threat to property and
      infrastructure, and preventing further instream gravel mining are postulated in
      order to arrest channel incision and reestablish the conditions for water and
      sediment storage on the floodplains.

PMID- 11531238
TI  - A procedure for incorporating spatial variability in ecological risk assessment
      of Dutch river floodplains.
AB  - Floodplain soils along the river Rhine in the Netherlands show a large spatial
      variability in pollutant concentrations. For an accurate ecological risk
      characterization of the river floodplains, this heterogeneity has to be included
      into the ecological risk assessment. In this paper a procedure is presented that
      incorporates spatial components of exposure into the risk assessment by linking
      geographical information systems (GIS) with models that estimate exposure for the
      most sensitive species of a floodplain. The procedure uses readily available site
      specific data and is applicable to a wide range of locations and floodplain
      management scenarios. The procedure is applied to estimate exposure risks to
      metals for a typical foodweb in the Afferdensche and Deestsche Waarden floodplain
      along the river Waal, the main branch of the Rhine in the Netherands. Spatial
      variability of pollutants is quantified by overlaying appropriate topographic and
      soil maps resulting in the definition of homogeneous pollution units. Next to
      that, GIS is used to include foraging behavior of the exposed terrestrial
      organisms. Risk estimates from a probabilistic exposure model were used to
      construct site-specific risk maps for the floodplain. Based on these maps,
      recommendations for future management of the floodplain can be made that aim at
      both ecological rehabilitation and an optimal flood defense.

PMID- 11531239
TI  - A simple method for predicting the consequences of land management in urban
      habitats.
AB  - Land management in urban areas is characterized by the diversity of its goals and
      its physical expression in the landscape, as well as by the frequency and often
      rapidity of change. Deliberate or accidental landscape alterations lead to
      changes in habitat, some of which may be viewed as environmentally beneficial,
      others as detrimental. Evaluating what is there and how changes may fit into the
      landscape context is therefore essential if informed land-management decisions
      are to be made. The method presented here uses a simple ecological evaluation
      technique, employing a restricted number of evaluation criteria, to gather a
      spatially complete data set. A geographical information system (GIS) is then used
      to combine the resulting scores into a habitat value index (HVI). Using examples
      from Wolverhampton in the United Kingdom, existing real-world data are then
      applied to land-management scearios to predict probable landscape ecological
      consequences of habitat alteration. The method provides an ecologically relevant,
      spatially complete evaluation of a large, diverse area in a short period of time.
      This means that contextual effects of land-management decisions can be quickly
      visualized and remedial or mitigating measures incorporated at an early stage
      without the requirement for complex modeling and prior to the detailed ecological
      survey. The strengths of the method lie in providing a detailed information
      baseline that evaluates all habitats, not just the traditional "quality"
      habitats, in a manner that is accessible to all potential users-from interested
      individuals to professional planners.

PMID- 11531240
TI  - A landscape ecological approach to address scaling problems in conservation
      management and monitoring.
AB  - Management of many African game reserves is today often still an art based on
      experience and intuition, rather than a science. Decision-making is based on an
      informal integration of accumulated individual knowledge and keen field
      observations. Data are generally poorly captured and curated. Until fairly
      recently, denominators of biological parameters (such as the unit of land or unit
      of plant production used as measurement) have generally been treated as being
      homogenous. The patchiness of landscapes and the issue of ecological scaling were
      ignored, often because of a lack of appropriate technical tools. The ecological
      data available on the 49,000-ha Songimvelo Game Reserve (SGR) result from a
      number of discrete survey and monitoring projects undertaken by different
      researchers, with different objectives, at different spatial and temporal scales.
      A landscape ecological approach towards research and monitoring is appropriate
      for an area of the size and diversity of the SGR. A combination of a database
      approach and spatial representation was used to consolidate and integrate data
      across temporal and spatial scales. Herbivore spatial and temporal distribution
      patterns were explored across three spatial scales. An understanding was achieved
      of the importance of landscape patchiness in controlling resource availability
      for herbivores. This insight is important in guiding management and monitoring of
      the SGR by placing perceived patch overutilization in its proper landscape
      context. The landscape ecological approach bridges the traditional scale
      independent view to a more contemporary scale-related understanding of ecosystem
      diversity and functioning.

PMID- 11531241
TI  - Rock climbers' attitudes toward management of climbing and the use of bolts.
AB  - The purpose of this research was to verify that various segments of the rock
      climbing community have different attitudes toward resource management and to aid
      in the understanding of attitudinal differences that can affect rock-climbing
      management. Respondents were given an on-site questionnaire; 400 usable surveys
      were collected from 13 different locations in the United States. Respondents
      identified themselves according to the type of climbing they participated in
      (e.g., traditional climbing, sport climbing, and hybrid climbing). Factor
      analysis identified five usable factors: bolt placement/use, need for management,
      reservations about management, appropriateness of bolts, and climbers' self
      perception. A repeated-measures analysis of variance identified significant
      differences among responses from traditional and sport climbers on four of the
      five scales used to measures attitudes. The variance among the climbing subgroups
      indicated that various climbing groups had significantly different attitudes
      toward management. All climbers surveyed had reservations about the management
      process. Results from the analysis indicated that climbers from all three groups
      (traditional, sport, and hybrid) felt that managers did not adequately understand
      the activity of climbing, climbers did not adequately understand the management
      process, climbing was not treated fairly in the management process in comparison
      to other activities, and climbing was micromanaged.

PMID- 11531242
TI  - Benefits-based analysis of visitor use of Sorak-san National Park in Korea.
AB  - Benefits-based management seeks to provide recreation benefits for recreation
      participants by managing the physical environments in which recreation occurs.
      This study investigates the relationship between benefits desired by visitors and
      the physical, social, and managerial characteristics of settings that facilitate
      realization of recreation benefits. Data such as perceived benefits from
      recreation experiences, setting attributes that significantly influenced
      perceived benefits, and sociodemographic variables were collected from 376
      visitors to Sorak-san National Park in the eastern part of the Korean peninsula.
      Cluster analysis was used to group visitors' desired benefits into 12 domains:
      relationship with nature/scenery, escaping pressure, learning about nature,
      family togetherness, introspection, exploration, autonomy/achievement, being with
      friends, leading others, skills/learning, risk taking, and meeting/observing new
      people. Multiple regression was used to link benefit domains with the
      characteristics of settings. The social attribute of recreation settings was
      linked to eight of the ten benefit domains. There were two statistically strong
      multiple regression correlations: (1) between domain of "relationship with
      nature/scenery" and the attributes "forest/water," "attractive nature," and
      "facility/maintenance" and (2) between the domain of "escaping pressure" and the
      attributes "attractive nature" and "social." The results of this study are useful
      to managers in their efforts to provide recreation opportunities for visitors to
      achieve beneficial outcomes.

PMID- 11531243
TI  - Variation in survival of women with breast cancer: Health Board remains a factor
      at 10 years.
AB  - Multivariate survival analysis of women with breast cancer diagnosed in 1987 with
      at least 10 years follow-up confirmed variations depending on the Health Board of
      their treatment. Differences in survival according to surgical
      caseload/specialization or deprivation were not statistically significant.

PMID- 11531244
TI  - Do men with prostate or colorectal cancer seek different information and support
      from women with cancer?
AB  - Male cancer patients' use of a national cancer information service, their
      requests and key predictors of these over the period April 1996 to March 1998 are
      presented, in comparison with women. The most frequent requests of 411 prostate,
      162 male and 217 female colorectal cancer patients were similar: site-specific
      information, emotional support, publications, specific therapies. Research or
      clinical trials (P < 0.05), diet and nutrition (P < 0.001) requests differed
      between men with prostate and colorectal cancers; complementary therapies (P <
      0.05), prognosis (P < 0.05) requests differed between male and female colorectal
      cancer patients. Among prostate cancer patients, employed men aged 60+ were more
      likely to need emotional support than retired men aged 70 +; men < 59 years old
      were more likely to request publications, but less likely to enquire about
      specific therapies than others. Among male colorectal cancer patients, employed
      men were less likely to request site-specific information, but more likely to
      need emotional support than retired men; patients from geographical areas other
      than Thames were more likely to request publications; patients from manual
      classes were less likely to enquire about specific therapies than those from non
      manual classes. The complexity of information and support seeking behaviour is
      demonstrated; no pattern was found among men or in comparison with women. Further
      research is needed to enable development of services that are appropriate to
      individual needs and concerns.

PMID- 11531246
TI  - Survey of the rate of PSA testing in general practice.
AB  - The use of prostate specific antigen (PSA) test could have a large impact on the
      incidence of prostate cancer in the UK. Over a period of 1 year (1999), 3.5% out
      of 160 015 men aged > 45 on a GP database, who had no previous record of prostate
      cancer, had a PSA test. Of the tested men, 21.3% had a PSA > 4 ng/ml. Future data
      need to distinguish between men with and without symptoms.

PMID- 11531245
TI  - Pemetrexed disodium in recurrent locally advanced or metastatic squamous cell
      carcinoma of the head and neck.
AB  - This phase II study determined response rate of patients with locally advanced or
      metastatic head and neck cancer treated with pemetrexed disodium, a new
      multitargeted antifolate that inhibits thymidylate synthase, dihydrofolate
      reductase and glycinamide ribonucleotide formyl transferase. 35 patients with
      local or metastatic relapse of squamous cell carcinoma of the head and neck (31
      male, 4 female; median age 53 years) were treated with pemetrexed 500 mg
      m(2)administered as a 10-minute infusion on day 1 of a 21-day cycle. Patients
      received 1 to 8 cycles of therapy. 9 patients (26.5%) had an objective response,
      with a median response duration of 5.6 months (range 2.9-20 months). 15 (44.1%)
      had stable disease, and 8 (23.5%) had progressive disease. 2 patients were not
      assessable for response. Median overall survival was 6.4 months (range 0.7-28.1
      months; 95% CI: 3.9-7.7 months). 24 patients (68.6%) experienced grade 3/4
      neutropenia, with febrile neutropenia in 4 (11.4%). Grade 3/4 anaemia and
      thrombocytopenia occurred in 11 (34.3%) and 6 (17.1%) patients, respectively. The
      most frequent non-haematological toxicity was grade 3/4 mucositis (17.1%; 6
      patients). In conclusion, pemetrexed is active in squamous cell carcinoma of the
      head and neck. Although substantial haematological toxicities were experienced by
      patients, subsequent studies have shown that these toxicities can be proactively
      managed by folic acid and vitamin B(12)supplementation.

PMID- 11531247
TI  - Risk of betel chewing for oesophageal cancer in Taiwan.
AB  - Among 104 cases of squamous-cell oesophageal carcinoma patients and 277 controls
      in Taiwan, after adjusting for cigarette smoking, alcohol consumption, and other
      confounders, we found that subjects who chewed from 1 to 495 betel-year and more
      than 495 betel-years (about 20 betel quid per day for 20 years) had 3.6-fold (95%
      Cl = 1.3-10.1) and 9.2-fold risk (95% Cl = 1.8-46.7), respectively, of developing
      oesophageal cancer, compared to those who did not chew betel.

PMID- 11531248
TI  - Betel nut and tobacco chewing; potential risk factors of cancer of oesophagus in
      Assam, India.
AB  - Cancer of the oesophagus is the most commonly diagnosed cancer in males in Assam,
      in north-eastern India, and ranks second for females. The chewing of betel nut,
      with or without tobacco and prepared in various ways, is a common practice in the
      region and a case-control study has been designed to study the pattern of risk
      associated with different ways of preparing and chewing the nuts. 358 newly
      diagnosed male patients and 144 female have been interviewed together with 2
      control subjects for each case chosen at random from among the attendants who
      accompanied patients to hospital. There were significant trends in risk ratios
      associated with the frequency of chewing each day, with the duration of chewing
      in years and with the age at which the habit was started that were apparent for
      both males and females and which remained significant after allowance was made
      for other known risk factors, notably tobacco smoking and alcohol consumption.
      The adjusted ratios, in comparison with non-chewers, were 13.3 M and 5.7 F for
      chewing more than 20 times a day, 10.6 M and 7.2 F for persons who had chewed for
      more than 20 years and 10.3 M and 5.3 F for those who had started before the age
      of 20. Among the different combinations of ingredients that were chewed the
      adjusted odds ratios were highest for those who had been using fermented betel
      nut with any form of tobacco (7.1 M and 3.6 F). The risk associated with tobacco
      smoking and alcohol consumption, which are high in some parts of the world, were
      less in Assam than those associated with the chewing of betel nut.

PMID- 11531249
TI  - Breast conservation, mastectomy and axillary surgery in New South Wales women in
      1992 and 1995.
AB  - To measure the increase in uptake of BCT in NSW and its determinants, we examined
      Cancer Registry records of 2020 women with breast cancer in 1992 and 2883 in 1995
      linked to records of their surgical treatment in the NSW Inpatient Statistics'
      Collection. In parallel, we examined trends and determinants in axillary surgery
      for breast cancer. Breast conservation increased from 39% of breast cancer in
      1992 to 45% in 1995, mainly in women with the smallest cancers. In 1995,
      mastectomy was still most common in women with larger cancers (OR for breast
      cancers 3+ cm relative to <1 cm = 5.6, 95% CI 2.9-10.7) and cancers that had
      spread beyond the breast (OR = 2.0, 95% CI 1.4-2.7 relative to localized to the
      breast). Urban women had fewer mastectomies than rural women. Axillary surgery,
      common in 1992 (78%) and 1995 (82%), fell steeply with increasing age and more
      often accompanied mastectomy (93% in 1995) than BCT (67% in 1995). In 1995 the
      odds for axillary surgery were some two-fold or more higher for all cancers 1 cm
      or more in diameter compared with those <1.0 cm and highest for 2.0-2.9 cm
      cancers (OR = 3.3 95% CI 1.7-6.7 relative to <1.0 cm). Regional spread of the
      cancer at diagnosis was not a strong predictor. In the absence of collection of
      treatment data by cancer registries, linkage of cancer registry records with
      hospital inpatient data is an effective alternative for monitoring breast cancer
      treatment trends.

PMID- 11531250
TI  - A population-based cohort study of HRT use and breast cancer in southern Sweden.
AB  - The overall tumour incidence and breast cancer incidence related to hormone
      replacement therapy (HRT) were followed in a population-based cohort of 29 508
      women, aged 25-65 when interviewed in 1990-92. By the end of the follow up in
      December 1999, there were 226 611 person-years of observation. A total of 1145
      malignant tumours were recorded (expected 1166.6; SIR = 0.98, 95% CI 0.93-1.04).
      There was a small excess of breast cancer with 434 observed and 387.69 expected
      (SIR = 1.12, 95% CI 1.02-1.23). Among about 3 663 ever users of HRT, there was no
      increase in overall tumour incidence (SIR = 0.98, 95% CI 0.86-1.12) but a
      significant excess of breast cancer (SIR = 1.35, 95% CI 1.09-1.64) compared with
      never users (SIR = 1.07, 95% CI 0.96-1.19). Breast cancer increased with
      increasing duration of use and for 48-120 months use the SIR was 1.92 (95% CI
      1.32-2.70). There was no significant interaction with family history of breast
      cancer although an independent additive effect was suggested between HRT use and
      family history. In a Cox regression model time to breast cancer in relation to
      duration of HRT use was analysed adjusting for age at menarche, age at menopause,
      age at first full term pregnancy, parity and age at diagnosis. A significantly
      higher risk was seen for longer duration of HRT use compared with never users. No
      increased risk is seen in women beyond 5 years after stopping HRT. There was no
      interaction between previous use of oral contraceptives and later HRT use.

PMID- 11531251
TI  - Risk of cancers of the lung, head and neck in patients hospitalized for
      alcoholism in Sweden.
AB  - Alcoholic patients are at increased risk of cancers of the head and neck but
      little information is available on the magnitude of the risk for specific sites
      and for different histological types. We followed 182 667 patients with a
      hospital discharge diagnosis of alcoholism during 1965-1994, for an average of
      10.2 years. We compared their incidence of site- and histological type-specific
      cancers of the oral cavity, pharynx, larynx and lung with that of the national
      population. The standardized incidence ratio (SIR) of cancer of the oral cavity
      and pharynx was 5.33 (95% confidence interval [CI] 5.04-5.64, based on 1207
      cases). The SIRs of laryngeal and lung cancer were 4.21 (95% Cl 3.78-4.68, 347
      cases) and 2.40 (2.29-2.51, 1880 cases), respectively. The SIR was highest for
      cancers of the hypopharynx, floor of the mouth, mesopharynx and base of the
      tongue. The relative excess of lung cancer was similar for squamous cell
      carcinoma and adenocarcinoma. Low age at first hospitalization was associated
      with higher SIRs for all sites under study. 25 years after first hospitalization
      for alcoholism, the cumulative probability of developing a lung cancer was in the
      order of 5%, for oral and pharyngeal cancer it was 2.5%, and for oesophageal or
      laryngeal cancer 1% each. Our study shows that the risk of head and neck cancer
      among heavy drinkers is highest for sites in direct contact with alcohol. The
      high risk of head and neck neoplasms may justify specific medical attention.

PMID- 11531252
TI  - Non-melanoma skin cancers and glucocorticoid therapy.
AB  - Non-melanoma skin cancer (NMSC) is an important cause of morbidity and long-term
      mortality in organ transplant recipients receiving immunosuppressive drugs such
      as azathioprine and cyclosporin, often combined with adrenocortical steroids
      (glucocorticoids). At lower doses, glucocorticoids alone are prescribed for other
      conditions including musculoskeletal, connective tissue and respiratory
      disorders. Presently, it is unknown whether patients taking glucocorticoids are
      at an increased risk of skin malignancies. In a population-based case-control
      study in New Hampshire, USA, we compared use of glucocorticoids in 592 basal cell
      carcinoma (BCC) and 281 squamous cell carcinoma (SCC) cases and in 532 age and
      gender matched controls; neither cases nor controls had a history of organ
      transplantation. Participants underwent a structured personal interview regarding
      history of medication use and skin cancer risk factors. We used unconditional
      logistic regression analysis to compute odds ratios associated with
      glucocorticoid use for 1 month or longer while controlling for potential
      confounding factors. Risk of SCC was increased among users of oral
      glucocorticoids (adjusted odds ratio = 2.31; 95% CI = 1.27, 4.18), and risk of
      BCC was elevated modestly (adjusted odds ratio = 1.49; 95% CI = 0.90, 2.47). In
      contrast, risk of both SCC and BCC were unrelated to use of inhaled steroids. Our
      data suggest that use of oral glucocorticoids may increase risk of NMSC, and SCC
      in particular, among patients other than organ transplant recipients. We
      hypothesize that immunosuppression induced by oral glucocorticoids may allow
      these cancers to emerge from immunosurveillance.

PMID- 11531253
TI  - Analysis of the TGF beta functional pathway in epithelial ovarian carcinoma.
AB  - Epithelial ovarian carcinoma is often diagnosed at an advanced stage of disease
      and is the leading cause of death from gynaecological neoplasia. The genetic
      changes that occur during the development of this carcinoma are poorly
      understood. It has been proposed that IGFIIR, TGFbeta1 and TGFbetaRII act as a
      functional unit in the TGFbeta growth inhibitory pathway, and that somatic loss
      of-function mutations in any one of these genes could lead to disruption of the
      pathway and subsequent loss of cell cycle control. We have examined these 3 genes
      in 25 epithelial ovarian carcinomas using single-stranded conformational
      polymorphism analysis and DNA sequence analysis. A total of 3 somatic missense
      mutations were found in the TGFbetaRII gene, but none in IGFRII or TGFbeta1. An
      association was found between TGFbetaRII mutations and histology, with 2 out of 3
      clear cell carcinomas having TGFbetaRII mutations. This data supports other
      evidence from mutational analysis of the PTEN and beta-catenin genes that there
      are distinct developmental pathways responsible for the progression of different
      epithelial ovarian cancer histologic subtypes.

PMID- 11531255
TI  - Frequent genomic imbalances suggest commonly altered tumour genes in human
      hepatocarcinogenesis.
AB  - Hepatocellular carcinoma (HCC) is one of the most frequent-occurring malignant
      tumours worldwide, but molecular changes of tumour DNA, with the exception of
      viral integrations and p53 mutations, are poorly understood. In order to search
      for common macro-imbalances of genomic tumour DNA, 21 HCCs and 3 HCC-cell lines
      were characterized by comparative genomic hybridization (CGH), subsequent
      database analyses and in selected cases by fluorescence in situ hybridization
      (FISH). Chromosomal subregions of 1q, 8q, 17q and 20q showed frequent gains of
      genomic material, while losses were most prevalent in subregions of 4q, 6q, 13q
      and 16q. Deleted regions encompass tumour suppressor genes, like RB-1 and the
      cadherin gene cluster, some of them previously identified as potential target
      genes in HCC development. Several potential growth- or transformation-promoting
      genes located in chromosomal subregions showed frequent gains of genomic
      material. The present study provides a basis for further genomic and expression
      analyses in HCCs and in addition suggests chromosome 4q to carry a so far
      unidentified tumour suppressor gene relevant for HCC development.

PMID- 11531254
TI  - Kirsten ras mutations in patients with colorectal cancer: the 'RASCAL II' study.
AB  - Researchers worldwide with information about the Kirsten ras (Ki-ras) tumour
      genotype and outcome of patients with colorectal cancer were invited to provide
      that data in a schematized format for inclusion in a collaborative database
      called RASCAL (The Kirsten ras in-colorectal-cancer collaborative group). Our
      results from 2721 such patients have been presented previously and for the first
      time in any common cancer, showed conclusively that different gene mutations have
      different impacts on outcome, even when the mutations occur at the same site on
      the genome. To explore the effect of Ki-ras mutations at different stages of
      colorectal cancer, more patients were recruited to the database, which was
      reanalysed when information on 4268 patients from 42 centres in 21 countries had
      been entered. After predetermined exclusion criteria were applied, data on 3439
      patients were entered into a multivariate analysis. This found that of the 12
      possible mutations on codons 12 and 13 of Kirsten ras, only one mutation on codon
      12, glycine to valine, found in 8.6% of all patients, had a statistically
      significant impact on failure-free survival (P = 0.004, HR 1.3) and overall
      survival (P = 0.008, HR 1.29). This mutation appeared to have a greater impact on
      outcome in Dukes' C cancers (failure-free survival, P = 0.008, HR 1.5; overall
      survival P = 0.02, HR 1.45) than in Dukes' B tumours (failure-free survival, P =
      0.46, HR 1.12; overall survival P = 0.36, HR 1.15). Ki-ras mutations may occur
      early in the development of pre-cancerous adenomas in the colon and rectum.
      However, this collaborative study suggests that not only is the presence of a
      codon 12 glycine to valine mutation important for cancer progression but also
      that it may predispose to more aggressive biological behaviour in patients with
      advanced colorectal cancer.

PMID- 11531256
TI  - Clinical and molecular stratification of disease risk in medulloblastoma.
AB  - The accurate assessment of disease risk among children with medulloblastoma
      remains a major challenge to the field of paediatric neuro-oncology. In the
      current study we investigated the capacity of molecular abnormalities to increase
      the accuracy of disease risk stratification above that afforded by clinical
      staging alone. 41 primary medulloblastoma tumour samples were analysed for ErbB2
      receptor expression using immunohistochemistry, and for aberrations of chromosome
      17 and amplification of the MYC oncogene using fluorescence in situ
      hybridisation. The ErbB2 receptor and deletion of 17p were detected in 80% and
      49% of tumours, respectively. 17p loss occurred either in isolation (20%), or in
      association with gain of 17q (29%), compatible with an isochromosome of 17q.
      Amplification of MYC was detected in only 2 tumours. Significant prognostic
      factors included, 'metastatic disease' (P = 0.0006), 'sub-total tumour resection'
      (P = 0.007), 'high ErbB2 receptor expression' (P = 0.003) and 'isolated 17p loss'
      (P = 0.003). Combined analysis of clinical and molecular factors enabled greater
      resolution of disease risk than clinical factors alone, identifying a sub
      population of patients with particularly favourable disease outcome. These data
      support the hypothesis that a combination of clinical and molecular factors may
      afford a more reliable means of assigning disease risk in patients with
      medulloblastoma, thereby providing a more accurate basis for targeting therapy in
      children with this disease.

PMID- 11531257
TI  - Expression of multiple cancer-testis antigen genes in gastrointestinal and breast
      carcinomas.
AB  - Cancer-testis antigens (CTAs) such as MAGE are selectively expressed in various
      types of human neoplasms but not in normal tissues other than testis. This
      characteristic feature of CTAs makes them promising antigens for cancer-specific
      immunotherapy. A critical requirement for this therapy is identification of
      promising antigens. In this study, we investigated the expression of 6 genes
      recently identified by serological analysis of antigens by recombinant expression
      (SEREX) libraries: NY-ESO-1, LAGE-1, SCP-1, SSX-1, SSX-2, and SSX-4, in many
      surgical samples of gastrointestinal and breast carcinomas using reverse
      transcription-polymerase chain reaction. We found relatively high expression of
      SCP-1 (23.5%) and SSX-4 (20.6%) in gastric carcinoma, LAGE-1 (39.1%) and NY-ESO-1
      (23.9%) in oesophageal carcinoma, and SCP-1 (34.1%) in breast carcinoma. We also
      found frequent synchronous expression with MAGE, including LAGE-1 (46.2%) in
      oesophageal carcinoma, SSX-4 (46.7%) in gastric carcinoma, and SCP-1 (38.3%) in
      breast carcinoma. Immunohistochemical analysis of the tumour samples expressing
      both MAGE-4 and NY-ESO-1 genes demonstrated differences in distribution between
      MAGE-4 and NY-ESO-1 in serial sections. We concluded that NY-ESO-1, LAGE-1, SCP-1
      and SSX-4 genes may be promising candidates for cancer-specific immunotherapy in
      addition to MAGE, and that polyvalent cancer vaccines may be useful in cases of
      heterogeneous expressions of CTA genes in gastrointestinal and breast carcinomas.

PMID- 11531259
TI  - ALA- and ALA-hexylester-induced protoporphyrin IX fluorescence and distribution
      in multicell tumour spheroids.
AB  - Synthesis of protoporphyrin IX (PpIX) in intact murine mammary cancer cell
      spheroids is reported from optical sections obtained using a laser scanning
      confocal fluorescence microscope. EMT6 spheroids 275-350 microm in diameter were
      incubated in 0.1-15 mM aminolevulinic acid (ALA) or 0.001-2 mM ALA-hexylester (h
      ALA) to test the ability of both pro-drugs to diffuse into the spheroids and
      induce PpIX production. Spheroids incubated with ALA show significant
      fluorescence nonuniformity for all concentrations, with the outermost cells
      exhibiting greater porphyrin fluorescence. Comparable levels of fluorescence
      throughout the optical section are achieved with approximately 100-fold lower h
      ALA concentrations, indicating that the interior cells maintain esterase activity
      and porphyrin synthesis and that h-ALA diffuses efficiently to the spheroid
      interior. Fluorescence gradients are less pronounced with h-ALA incubation, in
      part because of apparent saturation of esterase activity in the spheroid
      perimeter. Proliferating (Ki67 positive) and quiescent cell populations exhibit
      remarkably different h-ALA concentration dependencies. The incubation
      concentration resulting in maximum fluorescence with ALA is 10 mM, while the
      optimal concentration for h-ALA is 200-fold lower at 0.05 mM. Exceeding these
      optimal concentrations for both pro-drugs leads to an overall loss of
      fluorescence.

PMID- 11531258
TI  - TP53 mutations, amplification of P63 and expression of cell cycle proteins in
      squamous cell carcinoma of the oesophagus from a low incidence area in Western
      Europe.
AB  - In Europe, high incidence rates of oesophageal squamous cell carcinoma (SCCE) are
      observed in western France (Normandy and Brittany) and in north-eastern Italy.
      Analysis of TP53 mutations in tumours from these regions has shown a high
      prevalence of mutations at A:T basepairs that may result from DNA damage caused
      by specific mutagens. However, the spectrum of TP53 mutations in regions of low
      incidence is unknown. We report here TP53 mutation analysis in 33 SCCE collected
      in Lyon, an area of low incidence. These tumours were also examined for MDM2 and
      P63 amplification, and for expression of p16(INK4a/CDKN2a), cyclin E,
      p27(Kipl)and Cox2. TP53 mutations were detected in 36% of the cases (12/33). In
      contrast with regions of high incidence, the mutation spectrum did not show a
      high prevalence of mutations at A:T base pairs. P63 was amplified in 5/32 cases
      tested (15.5%). No amplification of MDM2 was found. Expression studies revealed
      frequent loss of p16(INK4a/CDKN2a)(46%) and p27(Kipl)(25%) expression, and
      frequent overexpression of Cyclin E (70%) and Cox2 (42%). Overall, these results
      indicate that in Europe, SCCE from areas of high and low incidence present a
      similar pattern of molecular alterations but differ by the type of TP53
      mutations.

PMID- 11531260
TI  - Modulation of endogenous beta-tubulin isotype expression as a result of human
      beta(III)cDNA transfection into prostate carcinoma cells.
AB  - Increases of individual beta tubulin isotypes in antimicrotubule drug resistant
      cell lines have been reported by several laboratories. We have previously
      described elevations in beta(III)and beta(IVa)isotypes in estramustine and
      paclitaxel resistant human prostate carcinoma cells. To investigate further the
      function of beta tubulin isotypes in antimicrotubule drug response, human
      prostate carcinoma cells that normally have very low to undetectable levels of
      beta(III)were stably transfected with beta(III)cDNA in pZeoSV system. An 18 bp
      haemagglutinin (HA) epitope tag was added at the 3' end prior to cloning into the
      vector. Cells were transfected with pZeoSV or pZeoSV-beta(III)plasmids and
      selected in the presence of Zeocin. Immunofluorescent staining of the
      transfectant cells have shown significant expression and incorporation of HA
      tagged beta(III)tubulin into cellular microtubules. Quantitation of Western blots
      revealed the HA-tagged beta(III)levels to be approximately 7-fold higher than the
      vector control cells. RT-PCR analysis confirmed the increase at the transcript
      level and also revealed a collateral increase of beta(II)and
      beta(IVb)transcripts. Cell viability assays indicated that sensitivity of
      beta(III)transfected cells to various antimicrotubule agents was similar to
      vector transfected cells: IC50 values for estramustine, paclitaxel, colchicine
      and vinblastine were 4 microM, 4 nM, 22 nM and 2 nM, respectively for both cell
      lines. Thus, overexpression of beta(III)isotype in human prostate carcinoma cells
      by stable transfection failed to confer antimicrotubule drug resistance to these
      cells. Counterregulatory increases of endogenous beta(II)and beta(IVb)tubulin
      isotypes in these beta(III)transfected cells may be a compensatory mechanism used
      by the cells to overcome the effects of elevated beta(III)levels on the cellular
      microtubules. These results highlight the difficulty in isolating the
      contribution of single tubulin isotypes in drug response studies.

PMID- 11531261
TI  - In vitro anti-tumour activity of alpha-galactosylceramide-stimulated human
      invariant Valpha24+NKT cells against melanoma.
AB  - alpha-galactosylceramide (KRN 7000, alpha-GalCer) has shown potent in vivo anti
      tumour activity in mice, including against melanoma and the highly specific
      effect of inducing proliferation and activation of human Valpha24+NKT-cells. We
      hypothesized that human Valpha24+NKT-cells activated by alpha-GalCer might
      exhibit anti-tumour activity against human melanoma. To investigate this,
      Valpha24+NKT-cells were generated from the peripheral blood of patients with
      melanoma after stimulation with alpha-GalCer pulsed monocyte-derived dendritic
      cells (Mo-DCs). Valpha24+NKT-cells did not exhibit cytolytic activity against the
      primary autologous or allogeneic melanoma cell lines tested. However,
      proliferation of the melanoma cell lines was markedly suppressed by co-culture
      with activated Valpha24+NKT-cells (mean +/- SD inhibition of proliferation 63.9
      +/- 1.3%). Culture supernatants of activated Valpha24+NKT-cell cultures
      stimulated with alpha-GalCer pulsed Mo-DCs exhibited similar antiproliferative
      activities against melanoma cells, indicating that the majority of the inhibitory
      effects were due to soluble mediators rather than direct cell-to-cell
      interactions. This effect was predominantly due to release of IFN-gamma, and to a
      lesser extent IL-12. Other cytokines, including IL-4 and IL-10, were released but
      these cytokines had less antiproliferative effects. These in vitro results show
      that Valpha24+NKT-cells stimulated by alpha-GalCer-pulsed Mo-DCs have anti-tumour
      activities against human melanoma through antiproliferative effects exerted by
      soluble mediators rather than cytolytic effects as observed against some other
      tumours. Induction of local cytokine release by activated Valpha24+NKT-cells may
      contribute to clinical anti-tumour effects of alpha-GalCer.

PMID- 11531262
TI  - Enhanced etoposide sensitivity following adenovirus-mediated human topoisomerase
      IIalpha gene transfer is independent of topoisomerase IIbeta.
AB  - The roles that the alpha and beta isoforms of topoisomerase II (topo II) play in
      anticancer drug action were determined using MDA-VP etoposide-resistant human
      breast cancer cells and a newly constructed adenoviral vector containing the topo
      IIalpha gene (Ad-topo IIalpha). MDA-VP cells were more resistant to etoposide
      than to amsacrine and had more resistance to etoposide than did MDA-parental
      cells. MDA-VP cells also expressed lower topo IIalpha RNA and protein levels than
      parental cells but had comparable topo IIbeta levels. After infection with Ad
      topo IIalpha, topo IIalpha, RNA and protein levels increased significantly, as
      did the cells' sensitivity to etoposide. In contrast, topo IIbeta levels remained
      constant with little alteration in the cells' sensitivity to amsacrine. Band
      depletion immunoblotting assays indicated that topo IIalpha was depleted in
      etoposide-treated, Ad-topo IIalpha-transduced MDA-VP cells but not in amsacrine
      treated cells. Topo IIbeta was depleted in amsacrine-treated, Ad-topo IIalpha-MDA
      VP cells, with little change in the topo IIalpha levels. These results suggest
      that topo IIalpha gene transfer does not alter topo IIbeta expression and that
      enhanced sensitivity to etoposide is therefore secondary to change in topo
      IIalpha levels. These studies support the theory that etoposide preferentially
      targets topo IIalpha, while amsacrine targets topo IIbeta.

PMID- 11531263
TI  - Telomerase reverse transcriptase and telomeric-repeat binding factor protein 1 as
      regulators of telomerase activity in pancreatic cancer cells.
AB  - Telomerase adds hexameric repeats of 5'-TTAGGG-3' termed telomeres to ends of
      chromosomal DNA. This enzyme has been implicated in cellular immortalization and
      cellular senescence. Recently, a number of relevant genes have been cloned,
      including these encoding three major components of human telomerase: human
      telomerase RNA component (hTR), human telomerase reverse transcriptase (hTERT),
      and telomerase-associated protein-1 (TEP1). Also important are genes encoding
      human telomeric-repeat binding factor protein (TRF) 1 and 2. To clarify
      mechanisms regulating telomerase activity, we studied telomerase activity, the
      telomeric restriction fragment (TRF) length and gene expression of these
      telomerase components and the telomeric-repeat binding factor proteins in
      sequential observation following X-irradiation of cultured pancreatic cancer
      cells. We previously reported that PANC-1 cells are better able to tolerate
      thermal stress, antineoplastic drugs, and exposure to tumour necrosis factor than
      MIAPaCa-2 cells. MIAPaCa-2 and PANC-1 cells were exposed to X-irradiation, their
      telomerase activity was increased at 2 days and then decreased gradually. Of the
      three telomerase components, only hTERT mRNA expression showed parallel changes.
      TRF length was stable just before and after X-irradiation. Among binding factor
      proteins, TRF1 mRNA showed reciprocal changes possibly directed toward
      maintaining a stable telomere length. In this study, our results demonstrate that
      not only hTERT but also TRF1 are important regulator of telomerase activity.

PMID- 11531264
TI  - Modulation of adipocyte G-protein expression in cancer cachexia by a lipid
      mobilizing factor (LMF).
AB  - Adipocytes isolated from cachectic mice bearing the MAC 16 tumour showed over a 3
      fold increase in lipolytic response to both low concentrations of isoprenaline
      and a tumour-derived lipid mobilizing factor (LMF). This was reflected by an
      enhanced stimulation of adenylate cyclase in plasma membrane fractions of
      adipocytes in the presence of both factors. There was no up-regulation of
      adenylate cyclase in response to forskolin, suggesting that the effect arose from
      a change in receptor number or G-protein expression. Immunoblotting of adipocyte
      membranes from mice bearing the MAC16 tumour showed an increased expression of
      Galphas up to 10% weight loss and a reciprocal decrease in Galpha. There was also
      an increased expression of Galphas and a decrease in Galpha in adipose tissue
      from a patient with cancer-associated weight loss compared with a non-cachectic
      cancer patient. The changes in G-protein expression were also seen in adipose
      tissue of normal mice administered pure LMF as well as in 3T3L1 adipocytes in
      vitro. The changes in G-protein expression induced by LMF were attenuated by the
      polyunsaturated fatty acid, eicosapentaenoic acid (EPA). This suggests that this
      tumour-derived lipolytic factor acts to sensitize adipose tissue to lipolytic
      stimuli, and that this effect is attenuated by EPA, which is known to preserve
      adipose tissue in cancer cachexia.

PMID- 11531265
TI  - Induction of apoptosis by the ADEPT agent ZD2767: comparison with the classical
      nitrogen mustard chlorambucil and a monofunctional ZD2767 analogue.
AB  - ZD2767P is a phenol mustard glutamate prodrug which is currently being developed
      for Antibody Directed Enzyme Prodrug Therapy (ADEPT). In ZD2767 ADEPT an active
      bi-functional alkylating drug, ZD2767D (4-[N,N-bis(2-iodoethyl)amino]phenol), is
      generated following cleavage of ZD2767P by the bacterial enzyme carboxypeptidase
      G2 (CPG2) which is targeted to the tumour by conjugation to the F(ab')(2)fragment
      of the anti-CEA antibody A5B7. The aim of the studies described here was to
      identify the mode of cell death induced by ZD2767P + CPG2 in comparison to the
      established nitrogen mustard chlorambucil. The contribution of bifunctional and
      monofunctional ZD2767 DNA lesions to cell death induction was investigated using
      a monofunctional ZD2767D analogue. Apoptosis in LoVo tumour cells was studied by
      three different methods (nuclear morphology, annexin V staining and TUNEL).
      Levels of apoptosis detected using the three assays were similar, and each drug
      treatment produced apoptosis at levels above those in control cells at
      concentrations which resulted in tumour cell growth inhibition. The bi-functional
      compounds, ZD2767P + CPG2 and chlorambucil, induced apoptosis in a concentration
      and time dependent manner, with equitoxic concentrations producing equivalent
      levels of apoptosis. In contrast, the mono-functional ZD2767D analogue at 100
      microM resulted in the maximal level of apoptosis at 25 h with no further
      increase over the following 72 h. These studies have demonstrated that apoptosis
      is the mechanism of cell death induced by the ZD2767 ADEPT system, and that
      levels of apoptosis produced by ZD2767 are similar to those observed at equitoxic
      concentrations of the classical nitrogen mustard chlorambucil. The mono
      functional ZD2767 analogue also induced apoptosis, but with a different time
      course and characteristics. In conjunction with previous data, these studies have
      shown that the potent activity of ZD2767 can be attributed to the ability of the
      compound to induce bifunctional DNA lesions and engage apoptosis.

PMID- 11531267
TI  - TNM classification: clarification of number of regional lymph nodes for pN0.

PMID- 11531266
TI  - Initiation of human colon cancer cell proliferation by trypsin acting at protease
      activated receptor-2.
AB  - The protease-activated receptor-2 (PAR-2) is a G protein-coupled receptor that is
      cleaved and activated by trypsin. We investigated the expression of PAR-2 and the
      role of trypsin in cell proliferation in human colon cancer cell lines. A total
      of 10 cell lines were tested for expression of PAR-2 mRNA by Northern blot and RT
      PCR. PAR-2 protein was detected by immunofluorescence. Trypsin and the peptide
      agonist SLIGKV (AP2) were tested for their ability to induce calcium mobilization
      and to promote cell proliferation on serum-deprived cells. PAR-2 mRNA was
      detected by Northern blot analysis in 6 out of 10 cell lines [HT-29, Cl.19A, Caco
      2, SW480, HCT-8 and T84]. Other cell lines expressed low levels of transcripts,
      which were detected only by RT-PCR. Further results were obtained with HT-29
      cells: (1) PAR-2 protein is expressed at the cell surface; (2) an increase in
      intracellular calcium concentration was observed upon trypsin (1-100 nM) or AP2
      (10-100 microM) challenges; (3) cells grown in serum-deprived media supplemented
      with trypsin (0.1-1 nM) or AP2 (1-300 microM) exhibited important mitogenic
      responses (3-fold increase of cell number). Proliferative effects of trypsin or
      AP2 were also observed in other cell lines expressing PAR-2. These data show that
      subnanomolar concentrations of trypsin, acting at PAR-2, promoted the
      proliferation of human colon cancer cells. The results of this study indicate
      that trypsin could be considered as a growth factor and unravel a new mechanism
      whereby serine proteases control colon tumours.

PMID- 11531268
TI  - Alternative cancer cures.

PMID- 11531270
TI  - Gynecological tumors in hereditary nonpolyposis colorectal cancer: We know they
      are common--now what?

PMID- 11531271
TI  - The clinical features of ovarian cancer in hereditary nonpolyposis colorectal
      cancer.
AB  - OBJECTIVE: Hereditary nonpolyposis colorectal cancer (HNPCC) is a hereditary
      cancer susceptibility disorder associated with a very high risk for carcinoma of
      the colon and an elevated risk for certain extracolonic cancers including ovarian
      cancer. Our aim in this study was to describe the clinicopathologic features of
      ovarian cancer in HNPCC family members. METHODS: . Members of the International
      Collaborative Group on HNPCC collected retrospective data on 80 ovarian cancer
      patients who were members of HNPCC families, including 31 known mutation
      carriers, 35 presumptive carriers (by colorectal/endometrial cancer status), and
      14 at-risk family members. RESULTS: Mean age at diagnosis of ovarian cancer was
      42.7. Nonepithelial tumors made up only 6.4% of the cancers, and borderline
      tumors comprised just 4.1% of the epithelial cancers. Among frankly malignant
      epithelial cases, most cancers were well or moderately differentiated, and 85%
      were FIGO stage I or II at diagnosis. Synchronous endometrial cancer was reported
      in 21.5% of cases. CONCLUSIONS: Ovarian cancer in HNPCC differs from ovarian
      cancer in the general population in several clinically important respects. It
      occurs at a markedly earlier age. It is more likely to be epithelial. If it is a
      frankly invasive epithelial cancer, it is more likely to be well or moderately
      differentiated. HNPCC patients with ovarian cancer are more likely to have a
      synchronous endometrial cancer than other ovarian cancer patients and are more
      likely to be diagnosed at an early stage.

PMID- 11531272
TI  - Transcriptional targeting for ovarian cancer gene therapy.
AB  - Ovarian carcinoma is a leading cause of cancer death in women. Though advances in
      conventional therapies have been achieved, long-term survival rates for most
      patients diagnosed with ovarian cancer are still low. Therefore, novel molecular
      therapeutic strategies such as gene therapy are being intensively pursued. Such
      approaches are based on the enormous progress that has been achieved in the
      elucidation of the molecular foundations of ovarian cancer. In this regard
      transcriptional control elements (promoters) of genes frequently upregulated or
      specifically expressed in tumors can be applied in a heterologous context to
      drive expression of therapeutic genes in targeted gene therapy strategies. This
      review discusses transcriptional targeting strategies in ovarian cancer gene
      therapy and gives an overview of tumor-specific promoters (TSPs) that have been
      applied for this purpose.

PMID- 11531273
TI  - Cell cycle aberrations in the pathogenesis of squamous cell carcinoma of the
      uterine cervix.
AB  - Cancer cells are characterized by limitless proliferative autonomy and immunity
      to inhibitory and apoptotic signals, thus ensuring growth and metastasis [1].
      Epidemiological studies have long implicated human papillomavirus (HPV) as a
      pathogenic agent in cervical cancer. Progress in cancer research now provides an
      understanding of how these characteristics are achieved by the interaction of HPV
      proteins with the cell cycle machinery. Expression of oncoproteins E7 and E6
      induces immortalization of cells through their inhibitory effects on tumor
      suppressor proteins pRb and p53, respectively. Undermining of pRb's growth
      inhibitory role with release of E2F transcription factors renders the cells
      independent of mitogenic stimuli. The abundance of growth transcription factors
      grants limitless proliferative potential by allowing expression of products such
      as cyclins A, E, and B, dihydrofolate reductase, and DNA polymerase which fuel
      the various stages of the cell cycle. There is subsequent disruption of both the
      G1-S and G2-M cell cycle checkpoints. Overexpression of cyclin E results in
      chromosomal instability and possible unmasking of genetic mutations, allowing
      disease progression. Cyclin A grants anchorage-independent growth, facilitating
      tissue invasion and tumor spread. Apoptotic and growth-inhibitory mechanisms are
      also evaded. p53 is degraded by E6 and its own downstream protein mdm2. Its other
      downstream protein, p21 is rendered ineffective against cyclin-cyclin-dependent
      kinase units by E7, as is p27. The understanding of the molecular pathology of
      disease will provide us with the ability to prognosticate and treat patients more
      effectively.

PMID- 11531274
TI  - Bartholin's gland carcinoma: a 15-year experience.
AB  - OBJECTIVE: Our objective was to review our experience with carcinoma of
      Bartholin's gland relative to treatment and oncologic outcome. METHODS: Patient
      names were collected from our vulvar cancer database for the period September
      1985 to September 2000. The medical records were retrospectively reviewed, and
      data were abstracted relative to demographics, presenting symptoms, treatment,
      and oncologic outcome. RESULTS: We treated 12 women with Bartholin's gland
      carcinoma, and 11 patients are reported. Seven women presented with a painless
      vulvar mass, and 8 of 11 had initially been treated for an infectious process
      before referral to our institution. Squamous histology was most common, and the
      right gland was more frequently involved. Ten patients were treated with primary
      surgery, followed by adjuvant radiation in 7 for inadequate resection margins or
      lymphatic metastases. One patient was treated with primary chemoradiation. Stage
      I, II, III, IVA, and IVB disease was present in 3, 1, 4, 2, and 1 patient,
      respectively. Recurrence was suffered by 54.5% during a mean follow-up time of
      73.5 months (median, 60; range, 8-180 months). Overall survival is 58.3% to date.
      CONCLUSIONS: Conventional therapy for Bartholin's gland carcinoma yielded a 67% 5
      year survival. Seventy-one percent of women receiving adjuvant radiotherapy
      recurred despite this precaution. Work is needed to identify an effective
      systemic therapy and to better determine which patients may benefit from pelvic
      radiotherapy.

PMID- 11531275
TI  - Effect of hemodilution on tissue perfusion and blood coagulation during radical
      hysterectomy.
AB  - OBJECTIVE: The goal of this study was to evaluate the safety of hemodilution on
      global and splanchnic perfusion and blood coagulation during radical
      hysterectomy. METHODS: A pulmonary artery catheter and a gastric tonometry
      catheter were placed in 16 patients with cervical carcinoma. Global perfusion
      indices, splanchnic perfusion index, and coagulation tests were obtained. Blood
      was removed to achieve a hemoglobin measurement of 8-9 9 g/dL. Three more
      measurements were repeated after hemodilution, at the end of surgery, and after
      the retransfusion of blood. Analysis of variance was used to determine
      statistical significance. RESULTS: Sixteen patients with cervical carcinoma had
      1.0 +/- 0.3 L (mean +/- SD) of blood removed and had a blood loss of 0.8 +/- 0.7
      L. Hemodiluted preoperative hemoglobin was 8.7 +/- 1 g/dL. All of the global
      perfusion indices, except for arterial pH and oxygen consumption, decreased after
      hemodilution and recovered with the retransfusion of blood (P < or = 0.004).
      Splanchnic perfusion and coagulation tests were unchanged (P > or = 0.1). Major
      complication was pulmonary edema in one patient. CONCLUSION: Hemodilution during
      radical hysterectomy, in this select group of patients, does not appear to
      compromise tissue perfusion or coagulation.

PMID- 11531276
TI  - Telomerase activity in sex cord-stromal tumors of the ovary.
AB  - OBJECTIVE: Telomerase is a ribonucleoprotein that protects chromosomes from
      degradation and end-to-end fusions by maintaining telomere length. Studies have
      shown that telomerase is present in 95% of gynecologic malignancies and in 88% of
      epithelial ovarian carcinomas but undetectable in benign tissue. The aim of this
      investigation was to determine whether telomerase is present in sex cord-stromal
      tumors and whether telomerase activity is indicative of patient outcomes.
      METHODS: Forty-five consecutive sex cord-stromal ovarian tumors were analyzed by
      using reverse transcription-polymerase chain reaction for expression of human
      telomerase, human telomerase reverse transcriptase, and telomerase activity.
      RESULTS: Of the 29 patients with malignant cell types (granulosa cell, Sertoli
      Leydig cell, and steroid cell tumors), 21 of the 28 patients (75%) available for
      follow-up had recurrence, with a mean follow-up of 86 months (95% CI, 36-157
      months). The telomerase repeat amplification protocol assay had a sensitivity of
      74% and specificity of 94% for malignancy. Patients with telomerase-positive
      tumors had a mean disease-free interval of 66.5 months; for those with telomerase
      negative tumors the interval was 90 months. In addition, patients with telomerase
      positive tumors were more likely to be dead from disease or alive with disease
      than those without telomerase activity, and they showed trends toward requiring a
      larger number of surgical procedures for the treatment of their disease. However,
      these trends were not statistically significant. CONCLUSION: Although activation
      of telomerase is clearly an important step in carcinogenesis, it is unlikely to
      be helpful in the clinical management of sex cord-stromal tumors of the ovary.

PMID- 11531277
TI  - DNA methylation and ovarian cancer. I. Analysis of CpG island hypermethylation in
      human ovarian cancer using differential methylation hybridization.
AB  - OBJECTIVE: The aim of this study was to examine CpG island methylation patterns
      in ovarian cancer and determine whether epigenetic information can be related to
      clinical data of patients. CpG island (CpGI) hypermethylation is commonly
      associated with cancer progression, but little is currently known about the role
      of methylation in ovarian cancer. METHODS: Differential methylation hybridization
      (DMH) analysis at 742 loci was performed to determine methylation signatures for
      20 primary epithelial ovarian carcinomas (Stages II, III, and IV adenocarcinomas,
      serous papillary), 6 ovarian cancer cell lines, and normal ovarian surface
      epithelial cells. RESULTS: Between 23 and 108 methylated CpGIs were seen in the
      ovarian carcinomas. Fewer (P < 0.05) methylated CpGIs were observed in the
      ovarian cancer cell lines; however, a number of CpGIs were commonly
      hypermethylated in both the cell lines and the tumor samples. A methylation
      signature, consisting of frequently (P < 0.05) methylated CpGIs, was determined
      for the samples. The observed pattern of methylation in ovarian cancers included
      several (11) CpGI tags that were previously reported to be hypermethylated in
      human breast cancer. CONCLUSIONS: Epigenetic signatures in ovarian cancer were
      determined using DMH. This proof-of-concept study lays the foundation for genome
      wide screening of methylation to examine epigenotype-phenotype relationships in
      ovarian cancer.

PMID- 11531278
TI  - Low incidence of HPV DNA in sera of pretreatment cervical cancer patients.
AB  - OBJECTIVE: The aim of this study was to investigate the feasibility of using DNA
      in the circulation as a diagnostic tool for cervical cancer. METHODS: We used PCR
      followed by Southern hybridization to detect human papillomavirus (HPV) DNA in
      serum samples taken from patients of cervical cancer before treatment. RESULTS: A
      total of 60 samples were analyzed. In a set of 40 samples, without knowledge of
      the HPV DNA status in the corresponding cervical carcinomas, we could detect 8
      (20%) positive samples, of which 7 (17.5%) were HPV 16 and 1 (2.5%) was HPV 18.
      In another set of 20 samples, known to be HPV 16 infected in the corresponding
      cervical carcinomas, we detected only 4 (20%) HPV-16-positive samples. The
      occurrence of HPV DNA in sera of cervical cancer patients seems sporadic.
      CONCLUSION: The low incidence indicates that serum HPV DNA has limited
      application in the diagnosis of cervical cancer.

PMID- 11531279
TI  - Thrombospondin-1 expression in epithelial ovarian carcinoma: association with p53
      status, tumor angiogenesis, and survival in platinum-treated patients.
AB  - OBJECTIVE: The regulation of the metastatic process in epithelial ovarian cancer
      has not been well defined. Similar to other tumor types, the angiogenic phenotype
      in ovarian cancer strongly influences clinical outcome, suggesting that the
      acquisition of a pro-angiogenic environment is essential to the process of
      ovarian cancer proliferation and metastasis. Thrombospondin-1 (TSP-1) is a potent
      peptide shown in other tumor systems to be associated with angiogenesis and
      possibly regulated by p53, a gene which is mutated in as high as 50% of advanced
      ovarian cancers. The purpose of this study was to investigate TSP-1 expression in
      invasive epithelial ovarian cancer and to examine the relationship between TSP-1
      expression and the degree of angiogenesis. In addition, we examined whether TSP-1
      expression was associated with overexpression of p53. METHODS: Frozen sections
      obtained from 85 patients with invasive epithelial ovarian cancer were examined
      immunohistochemically for expression of TSP-1 and p53. The sections were examined
      microscopically by two investigators, who were blinded to the clinicopathologic
      variables. Outcome variables included the correlation among TSP-1, angiogenesis,
      and p53, as well as the association between TSP-1 expression and survival.
      RESULTS: The majority (62%) of cases demonstrated high levels (3+) of TSP-1
      expression; 7% demonstrated no TSP-1 expression. p53 was overexpressed in 55% of
      cases, and expression was inversely correlated with TSP-1 staining. Thirteen
      cancers had 0 or 1+ TSP-1 staining; 12 (92%) of these overexpressed the p53
      protein. In contrast, only 49% of tumors with high expression of TSP-1 have
      overexpression of p53 (P = 0.02). TSP-1 was suggestive for improved survival in
      patients with advanced disease; high TSP-1 expression was associated with a
      median survival of 2.4 years compared to 1.5 years for patients with tumors
      having a lower degree of TSP-1 expression (P = 0.06). CONCLUSION: These data
      suggest that TSP-1 may possess a tumor inhibitory function in patients with
      advanced epithelial ovarian carcinoma. The reduction of TSP-1 expression
      associated with overexpression of p53 may be coupled with the development of a
      pro-angiogenic environment and malignant phenotype.

PMID- 11531280
TI  - Preoperative hysteroscopic assessment of cervical invasion by endometrial
      carcinoma: a retrospective study.
AB  - OBJECTIVE: The aim of this study was to evaluate the efficacy of hysteroscopy,
      using normal saline (NS) or carbon dioxide (CO2) as the distention medium, in
      assessing tumor invasion of the uterine cervix by endometrial carcinoma. METHODS:
      A retrospective study was conducted in 200 consecutive patients with endometrial
      carcinoma diagnosed from 1993 to 2000. Prior to definitive surgical treatment,
      hysteroscopy was performed using either NS or CO2 as the distention medium to
      determine whether the tumor had spread to the cervix. The uterine specimens
      obtained after hysterectomies were cut open for gross examination. Tumor invasion
      of the cervix as determined by hysteroscopy and gross examinations was compared
      with the pathological findings. RESULTS: Tumor invasion of the cervix was found
      in 41 (20.5%) cases on pathological examination. Hysteroscopy has an accuracy of
      92.5% (185/200), a sensitivity of 68.3% (28/41), and a specificity of 98.7%
      (157/159), with a PPV of 93.3% (28/30) and a NPV of 92.4% (157/170) in
      determining cervical involvement. Assessment by gross inspection had 93.0%
      (186/200) accuracy, 68.3% (28/41) sensitivity, 99.4% (158/159) specificity, 96.6%
      (28/29) PPV, and 92.4% (158/171) NPV. There was no significant difference between
      the two assessment methods. When the results of hysteroscopy performed with
      different distention mediums were compared, the use of NS had a higher accuracy
      in determining tumor spread to the cervix (96.8% vs 88.7%, P = 0.03) and NPV
      (96.4% vs 88.4%, P < 0.05) than the use of CO2. CONCLUSIONS: Hysteroscopic
      assessment and gross examination of the uterine specimen had similar efficacy in
      detecting cervical invasion by endometrial carcinoma. Hysteroscopic examination
      using NS is more accurate than that which uses CO2.

PMID- 11531281
TI  - FHIT (fragile histidine triad) gene analysis in cervical intraepithelial
      neoplasia.
AB  - OBJECTIVE: Recently a candidate tumor suppressor gene, FHIT (fragile histidine
      triad), was identified at chromosome 3p14.2. Abnormality of this gene has been
      observed in a variety of human tumors. Although aberrant FHIT transcripts in a
      substantial percentage of cervical cancer cell lines and primary cervical tumors
      were also noted, some other studies revealed different results. Therefore, its
      association with the development of cervical cancer is still debatable. Because
      allelic loss in chromosome 3p is also a frequent finding in cervical
      intraepithelial neoplasia (CIN), we compared the transcription pattern and
      expression of FHIT in the preinvasive cervical lesions and normal cervical
      epithelia to investigate its possible role in cervical carcinogenesis. METHODS:
      Thirty-five consecutive CIN lesions taken from conization specimens and 33 normal
      cervical epithelial tissues taken from hysterectomy for benign diseases were
      included in this study. Total RNA was extracted from the pathology-confirmed
      tissue samples and first-strand cDNA was synthesized. It was amplified using a
      nested reverse transcription polymerase chain reaction (RT-PCR) method. The PCR
      products were then subjected to subcloned sequence analysis. Paraffin blocks from
      all of the samples were selected and prepared for immunohistochemical study with
      an anti-FHIT polyclonal antibody. RESULTS: All the cDNAs of CIN and normal
      cervical epithelial tissues showed the expected size of RT-PCR product. However,
      7 of the 35 (20%) CIN lesions and 5 of the 33 (15%) normal cervical epithelia
      also presented aberrant transcripts in addition to the normal-sized transcript of
      FHIT. Deletion of the cDNA segment covering exon 4 to exon 8 was the most
      frequent finding in the cases that showed abnormal FHIT transcripts. FHIT protein
      was intermediately or strongly expressed in most of the CIN lesions and normal
      squamous epithelia. However, reduced or absent FHIT expression was observed
      heterogeneously in the 7 CIN lesions and 5 normal cervices in which aberrant FHIT
      transcripts were detected. CONCLUSION: Because the normal-sized FHIT transcript
      was present robustly in all of the CIN lesions and the abnormal FHIT transcripts
      occurred with similar frequency and pattern in the CIN lesions and normal
      cervical tissues, we suggest that abnormal FHIT transcription might not be causal
      in the early process of cervical carcinogenesis.

PMID- 11531282
TI  - Expression of latent matrix metalloproteinase 9 (MMP-9) predicts survival in
      advanced ovarian cancer.
AB  - OBJECTIVE: Matrix metalloproteinases (MMPs) are frequently expressed in malignant
      tumors and play an important role in tumor invasion and metastasis. MMP-2 and MMP
      9 expression has been correlated with poor survival in some tumors, but data for
      ovarian cancer are lacking, despite clinical trials with MMP inhibitors. The aim
      of this study was to assess activity of MMP-2 and MMP-9 and correlate it to
      prognosis in ovarian cancer. METHODS: MMP-2 and MMP-9 gelatinolytic activity was
      analyzed in 84 patients with advanced ovarian cancer FIGO stage III and 19 benign
      ovarian tumors by gelatin zymography. MMP-9 immunoreactivity was detected by
      immunohistochemistry and gelatinolytic activity was localized in ovarian cancer
      tissue by in situ zymography. RESULTS: were correlated with patient survival,
      with a median follow-up period of 55 months. Results. Median pro-MMP-9 activity
      was at 0.00 U/microg protein in benign ovarian tissues and 4.82 U/microg protein
      in ovarian cancer (P = 0.001); activated MMP-9 was not detected. Pro-MMP-2
      expression in benign ovarian tissue did not differ from that of malignant ovarian
      tissue, whereas active MMP-2 was present in 52% of ovarian cancers, but absent in
      benign ovarian tissues. Analyzing all patients high pro-MMP-9 activity was
      associated with short overall survival (P = 0.019) while pro-MMP-2 and activated
      MMP-2 did not predict overall survival. When analyzing the subgroups of patients
      with and without residual tumor mass at the time of surgery, pro-MMP-9 was of
      prognostic value only in the subgroup of patients with no residual tumor mass. In
      univariate analysis pro-MMP-9 activity, residual tumor mass, age, ascites volume,
      and grading were of prognostic significance for overall survival. However, in
      multivariate analyses, including all biological and clinicopathologic variables,
      only pro-MMP-9 and residual disease remained statistically independent prognostic
      factors. In situ zymography localized gelatinolytic activity predominantly to the
      tumor cell nests displaying MMP-9 immunoreactivity. CONCLUSIONS: Pro-MMP-9
      gelatinolytic activity, but not active MMP-2 or MMP-9, serves as a useful
      statistically independent prognostic factor in ovarian cancer FIGO stage III,
      thus helping to identify ovarian cancer patients with an aggressive form of the
      disease.

PMID- 11531283
TI  - DNA methylation in ovarian cancer. II. Expression of DNA methyltransferases in
      ovarian cancer cell lines and normal ovarian epithelial cells.
AB  - OBJECTIVE: The aim of this study was to investigate whether expression of the
      enzymes that catalyze cytosine CpG island methylation, DNA methyltransferases,
      DNMT1, DNMT3a, and DNMT3b is altered in human ovarian cancer. Aberrations in DNA
      methylation are common in cancer and have important roles in tumor initiation and
      progression. Tumors that display frequent and concurrent inactivation of multiple
      genes by methylation are designated as having a CpG Island methylator phenotype,
      or CIMP. To date, colon, gastric, and most recently ovarian cancers meet the CIMP
      criteria for cancer. We hypothesized that altered expression of DNA
      methyltransferases can result in hypermethylation events seen in CIMP cancers.
      METHODS: DNMT1, DNMT3a, and DNMT3b mRNA levels in eight ovarian cancer cells
      lines (Hey, HeyA8, HeyC2, OVCAR-3, SK-OV-3, PA-1, A2780, and A2780-P5) were
      compared to DNMT expression in normal ovarian surface epithelial cells using semi
      quantitative reverse transcription-polymerase chain reaction. RESULTS: In HeyA8
      and HeyC2 ovarian cancer cells, DNMT1 expression levels were up to threefold
      higher (P < 0.05) than in normal ovarian surface epithelial cells. SK-OV-3 and PA
      1 displayed increased DNMT3b expression (P < 0.05) compared to normal ovarian
      surface epithelial cells. Transcript levels for DNMT3a, however, were similar in
      cancer and normal ovarian cells. CONCLUSIONS: We observed differential expression
      of the DNMT genes in some ovarian cancer cell lines and conclude that alterations
      in DNMT expression might contribute to the CIMP phenotype in ovarian cancer.
      However, based on the lack of aberrant DNMT expression in some of the cancer cell
      lines examined, we further suggest that another mechanism(s), in addition to DNMT
      overexpression, accounts for methylation anomalies commonly observed in ovarian
      cancer.

PMID- 11531285
TI  - A study of risk factors for ovarian metastases in stage Ib-IIIb cervical
      carcinoma and analysis of ovarian function after a transposition.
AB  - OBJECTIVE: The objective of the present study was to examine the incidence and
      risk factors of ovarian metastases in cervical carcinoma. The function of
      transposed ovaries was also studied. METHODS: In order to analyze the risk
      factors of ovarian metastases, 255 slides of pathological specimens were
      reassessed by multivariate logistic regression analysis. Fifty-six patients were
      studied prospectively on the basis of the function of transposed ovaries. Basal
      body temperature and serum hormone levels were analyzed. RESULTS: Ovarian
      metastasis was identified in 2 of 485 (0.4%) patients with squamous cell
      carcinoma and in 12 of 146 (8.2%) patients with nonsquamous tumors of the cervix.
      Histologic type (P = 0.0014) and blood vessel invasion (P = 0.0433) were
      significant independent risk factors for ovarian metastases, as revealed by
      multivariate logistic regression analysis. Cumulative survival curves of
      preserved ovaries showed a significant (P < 0.005) decline in the group with
      postoperative radiotherapy. CONCLUSION: Preservation of ovarian function should
      be pursued in patients with squamous cell carcinoma of the cervix, provided that
      the patient has no other risk factor (blood vessel invasion) for ovarian
      metastases. Moreover, sufficient attention should be paid to the proper handling
      of ovarian blood vessels during surgery, in order to shield and protect them from
      exposure to scattered radiation administered during postoperative radiotherapy.

PMID- 11531284
TI  - Profiling of protein kinases in the neoplastic transformation of human ovarian
      surface epithelium.
AB  - OBJECTIVE: The aim of this study was to study the pattern of protein kinase
      expression in a culture model of epithelial ovarian carcinogenesis. METHODS:
      Cultures of normal human ovarian surface epithelium (OSE), OSE from women with
      BRCA1 mutations, a cell culture model of preneoplastic (SV40 T-antigen
      immortalized, nontumorigenic) and neoplastic (SV40-E-cadherin transfected,
      tumorigenic) OSE, and three ovarian cancer cell lines were used to represent OSE
      phenotypes of different genetic backgrounds and at different, progressive stages
      of neoplastic transformation. The protein kinase network signaling was studied by
      Western blotting, simultaneously using multiple antibodies for specific protein
      kinases. RESULTS: High levels of cGMP-dependent protein kinase were found in
      normal and preneoplastic OSE, but were absent in neoplastic OSE. In contrast,
      expression of MEK6 was detected exclusively in neoplastic OSE. The expressions of
      casein kinase II (CK2), p38 mitogen-activated protein kinase (MAPK), cyclin
      dependent kinase, and the phosphatidylinositol 3-kinase (PI3K) effectors Akt2 and
      p70 S6 kinase (S6K) were several-fold higher in neoplastic OSE than in normal
      OSE, whereas the expressions of the MAPKs extracellular signal-regulated kinases
      ERK1 and -2 were unchanged. Importantly, constitutive phosphorylation of Akt2 and
      p70 S6K, as found in neoplastic OSE, was also observed in overtly normal OSE from
      women with predisposing BRCA1 gene mutations. CONCLUSIONS: These data demonstrate
      that different repertoires of downstream signaling proteins, particularly those
      of the MEK6-p38 MAPK-CK2 pathway and the PI3K pathway, are correlated with
      phenotypic manifestations of a cell culture model of OSE at progressive stages in
      the development of ovarian cancer. Changes in PI3K effectors are already found in
      overtly normal OSE from women with BRCA1 mutations.

PMID- 11531287
TI  - Liposomal doxorubicin in ovarian, peritoneal, and tubal carcinoma: a
      retrospective comparative study of single-agent dosages.
AB  - PURPOSE: The aim of this study was to evaluate the relative activity and
      tolerance of liposomal doxorubicin in recurrent ovarian, peritoneal, and tubal
      carcinoma at an initial dose of 40 or 50 mg/m(2) every 4 weeks. METHODS: A
      retrospective single-institution study was performed on patients who received
      liposomal doxorubicin from 1/97 to 12/00. Demographic data, liposomal doxorubicin
      dose, dose reductions, response, and progression-free and overall survival were
      recorded. RESULTS: Seventy-eight patients, 38 treated at 40 mg/m(2) and 40
      treated at 50 mg/m(2), were identified. There was no difference with respect to
      patient age, performance status, percentage of patients who were platinum
      resistant or paclitaxel resistant, or tumor bulk. The response rate in this
      highly resistant population was 13.5 and 7.7% for liposomal doxorubicin at 40 and
      50 mg/m(2) every 4 weeks, respectively. Stable disease was observed in 49 and 51%
      of patients treated with liposomal doxorubicin at a dose of 40 and 50 mg/m(2)
      every 4 weeks, respectively. The progression-free survival for patients with
      responding and stable disease was similar. Dose reductions were required in 27.5%
      of patients treated at 50 mg/m(2) versus no patients treated at 40 mg/m(2) (P <
      0.001). Treatment delays due to toxicity were required in 32.5% of patients
      treated at 50 mg/m(2) versus 16% of patients treated at 40 mg/m(2) (P = 0.14).
      CONCLUSION: Liposomal doxorubicin at a dose of 40 mg/m(2) appears to be as active
      as liposomal doxorubicin at a dose of 50 mg/m(2) in ovarian, peritoneal, and
      tubal carcinoma and is better tolerated based on the frequency of dose reductions
      and treatment delays.

PMID- 11531288
TI  - Predictors of complications after inguinal lymphadenectomy.
AB  - OBJECTIVE: The aim of this study was to identify predictors of complications in
      patients undergoing inguinal lymphadenectomy (LND) in the treatment of vulvar
      carcinoma. METHODS: Clinical information was abstracted from records of patients
      with invasive vulvar cancer. All patients underwent LND. Closed suction drains
      were placed in groin incisions and removed when output was less than 30 ml/24 h.
      Associations between variables were studied by chi(2) and t tests. RESULTS: Sixty
      seven patients undergoing 112 LND were evaluated. Eighty-eight percent of
      patients underwent radical vulvar surgery and LND while 12% underwent LND alone.
      Patients were treated with either unilateral (22) or bilateral (45) LND. Seventy
      three percent received extended postoperative prophylactic antibiotics. The
      median duration of suction drainage was 15 days for one drain and 14 days for two
      drains. Early postoperative cellulitis (<30 days after surgery) developed in
      35.4%, early wound breakdown in 19.4%, early lymphedema in 4.8%, and early
      lymphocyst formation in 13.1%. Late cellulitis (>30 days after surgery) developed
      in 22.2%, late wound breakdown in 3.2%, late lymphedema in 29.5%, and late
      lymphocysts in 5%. Patients developing early cellulitis were more likely to have
      early wound breakdown (P = <0.001, RR 14.2) or early lymphocyst formation (P =
      0.016, RR 7.6). Type of procedure, antibiotic use, need for adjuvant therapy, and
      duration of suction drainage did not influence early complications. Early
      complications and management strategies did not predict late complications.
      CONCLUSIONS: Chronic lymphedema occurs in nearly 30% of patients after LND. Late
      complications after LND were not predicted by early complications. New strategies
      for prevention of chronic lymphedema are needed.

PMID- 11531286
TI  - Phase II trial of oral altretamine for consolidation of clinical complete
      remission in women with stage III epithelial ovarian cancer: a Southwest Oncology
      Group trial (SWOG-9326).
AB  - OBJECTIVE: The aim of this study was to evaluate the 2-year survival rate in a
      group of women in complete clinical remission (cCR) from Stage III ovarian cancer
      following front-line therapy who were then treated with a 6-month course of
      altretamine. METHODS: Patients were documented to be in cCR by physical
      examination, computed tomography or magnetic resonance imaging scan, and serum CA
      125. Treatment consisted of altretamine (Hexalen) 260 mg/m(2)/day po divided into
      four doses taken after meals and at bedtime for 14 of 28 days for six cycles.
      Based on previous experience in the Southwest Oncology Group, the treatment would
      be considered promising if the 2-year survival rate was > or = 65% as measured
      from study registration. RESULTS: From 9/1/93 and 7/1/97, 112 patients were
      registered and 97 were fully evaluable. The majority of patients had optimally
      debulked (< or = 1 cm: 63%), high-grade (Grade 3: 82%) tumors. The 2-year
      survival rate in this study was 75% (95% CI: 66-84%). For those patients with
      optimal disease, the 2-year survival rate was 82% (95% CI: 72-92%) and for those
      with suboptimal disease it was 64% (95% CI: 48-79%). Four patients (4%)
      experienced Grade 4 and 21 patients (22%) experienced Grade 3 toxicities
      consisting primarily of nausea/vomiting, neutropenia, fatigue, anxiety, and
      paresthesias. CONCLUSIONS: The 2-year survival rate in this study warrants
      further evaluation of consolidation therapy for women in clinical complete
      remission following front-line chemotherapy for Stage III ovarian cancer. Caution
      is advised in the interpretation of these data, however, because of the
      nonrandomized nature of the trial and the unknown contribution of front-line use
      of paclitaxel to the durability of clinical complete response.

PMID- 11531289
TI  - Phase I trial of concomitant vinorelbine, paclitaxel, and pelvic irradiation in
      cervical carcinoma and other advanced pelvic malignancies.
AB  - OBJECTIVE: The aim of this study was to determine the feasibility and toxicity of
      concomitant vinorelbine, paclitaxel, and pelvic radiation therapy (RT) in
      patients with advanced cervical cancer and other pelvic malignancies. METHODS:
      Eligible patients included those with large or locally advanced cervical cancer.
      In addition, patients with other advanced gynecologic malignancies were eligible.
      In part I, vinorelbine was administered as a single agent during pelvic RT at a
      starting dose of 10 mg/m(2)/week with subsequent cohorts being escalated in 5
      mg/m(2)/week increments. In part II, paclitaxel was added to vinorelbine (20
      mg/m(2)/week) and pelvic RT at a starting dose of 20 mg/m(2)/week. RESULTS:
      Thirty-three women with pelvic malignancies (22 cervix, 6 vagina, 3 endometrium,
      2 vulva) were enrolled. Twenty-seven received vinorelbine and 6 received both
      paclitaxel and vinorelbine in combination with pelvic RT. Escalating vinorelbine
      doses to 25 mg/m(2)/week were well tolerated, with the primary toxicity being
      hematologic. RT was delayed in only 1 patient due to acute hematologic toxicity.
      In contrast, the combination of paclitaxel, vinorelbine, and pelvic RT was not
      well tolerated. Five of 6 patients (83%) experienced grade > or = 2 leukopenia,
      with 2 patients missing > 1 cycle of chemotherapy. Moreover, RT was delayed for 1
      week in 2 of 6 patients (33%). CONCLUSIONS: Concomitant pelvic RT and vinorelbine
      with doses to 25 mg/m(2)/week is well tolerated. The addition of paclitaxel to
      this combination is associated with significant hematologic toxicity and is thus
      not a feasible approach.

PMID- 11531290
TI  - Outcome of endometrial carcinoma patients with involvement of the uterine serosa.
AB  - OBJECTIVE: The goal of this work was to evaluate the outcome of endometrial
      carcinoma patients undergoing primary surgery who have serosal involvement (SI).
      METHODS: Between 1980 and 1998, 562 women underwent primary surgery for
      endometrial cancer at the University of Chicago. Thirty-nine were noted to have
      SI. FIGO stages were IIIA (19), IIIB (1), IIIC (7), and IV (12). Of the 19 IIIA
      patients, 15 had solitary SI. Twenty-six patients received pelvic radiation
      therapy (RT) with or without vaginal brachytherapy (VB). One patient received
      whole-abdomen radiation therapy, and 13, adjuvant chemotherapy. Solitary SI
      patients received pelvic RT with or without VB as their sole adjuvant therapy.
      Disease-free survivals (DFSs) were estimated using the method of Kaplan and Meier
      and prognostic factors were analyzed by the log-rank test. RESULTS: With a median
      follow-up of 30.3 months, the 5-year actuarial DFS of the entire group was 28.9%.
      Factors correlated with disease recurrence included tumor stage (P = 0.003) and
      lymph node involvement (P = 0.04). In addition, patients with solitary SI had a
      better 5-year DFS (41.5% vs 20%, P = 0.04) than patients with SI plus other
      extrauterine sites. Relapse occurred in 23 women overall and in 7 of 15 solitary
      SI patients. The most common site of disease recurrence was distant both in the
      entire group and in the solitary SI patients. While abdominal recurrences were
      common in the entire group, they were infrequent in solitary SI patients.
      CONCLUSION: Endometrial carcinoma patients with SI have a high rate of relapse
      and a poor outcome. Even when patients have extrauterine disease limited to SI,
      the outcome is relatively unfavorable. Nonetheless, our results demonstrate the
      need to distinguish patients with solitary SI and those with SI plus other
      extrauterine disease sites.

PMID- 11531291
TI  - Ovarian epithelial dysplasia in relation to ovulation induction and nulliparity.
AB  - OBJECTIVE: The goal of this study was to assess the relationship between
      ovulation induction, nulliparity, and ovarian epithelial dysplasia. METHODS: This
      retrospective cohort study was performed in one teaching and one district general
      hospital in London. The subjects, 83 women who had undergone hysterectomy and
      bilateral oophorectomy and whose ovaries were reported as "normal," were divided
      into three groups: ovulation induction (13), nulliparity (20), and fertile
      controls (50). These ovaries were independently reviewed by two pathologists who
      assigned a score of 0, 1, or 2 to nine epithelial cytological and architectural
      features. The main outcome measure was the total dysplasia score, which was used
      to quantify the degree of ovarian epithelial abnormality in the three groups.
      RESULTS: The mean dysplasia score was significantly higher in the women who had
      undergone ovulation induction than in the fertile controls (7.92 vs 5.70, P =
      0.012). The magnitude of the difference between the ovulation induction group and
      controls remained similar after adjusting for age, parity, and duration of oral
      contraceptive use (2.17, 95% CI: -0.11-4.44). However, the statistical
      significance of this difference was reduced (P = 0.062). We did not find any
      evidence of a difference in dysplasia score between nulliparous women and
      controls, neither before (P = 0.85) nor after adjusting for age and duration of
      oral contraceptive use (P = 0.87). CONCLUSIONS: These results suggest a possible
      association between ovarian epithelial dysplasia and ovulation induction therapy,
      in accord with previous reports of increased risk of ovarian cancer in women with
      a history of fertility treatment. The higher dysplasia score could be
      attributable to the drugs used to induce ovulation or to a genetic susceptibility
      to ovarian cancer.

PMID- 11531292
TI  - High sensitivity of PCR in situ hybridization for the detection of human
      papillomavirus infection in uterine cervical neoplasias.
AB  - OBJECTIVE: This study was designed in order to examine whether the sensitivity of
      PCR in situ hybridization (PISH) is superior to that of fluorescence in situ
      hybridization (FISH) and immunocytochemical staining (ICS) in detecting the
      presence of human papillomavirus (HPV) infection in uterine cervical neoplasias.
      METHODS: Three cell specimens were obtained from every 54 patients who had been
      histologically and cytologically diagnosed as severe dysplasia of the uterine
      cervix (SD), carcinoma in situ of the uterine cervix (CIS), or microinvasive
      carcinoma of the uterine cervix (MIC). All of them were first stained by the
      Papanicolaou (pap) method before the experiments. After specimens were classified
      into SD (n = 17) and CIS/MIC groups (n = 37), the sensitivities of detection for
      HPV infection were compared among PISH, FISH, and ICS methods which had been
      carried out after decolorization of the pap stain. RESULTS: In the SD group, PISH
      demonstrated a 58.8% positive incidence of HPV, which was significantly higher
      than that (23.5%) shown by FISH (P < 0.05). There was no significant difference
      in the positivities of HPV between the PISH and ICS (47.1%) methods. In the
      CIS/MIC group, PISH, FISH, and ICS showed 73.0, 43.2, and 54.1% positive
      incidences of HPV, respectively. There was significant difference in HPV
      positivities between PISH and FISH as well as ICS (P < 0.01, P < 0.05). The total
      frequency of the detection of HPV infection by PISH was significantly higher than
      that by FISH (P < 0.01) and high with a marginal significance compared to that by
      ICS (P = 0.051). Moreover, the morphologic change of a single cell and the HPV
      positive signals could be observed simultaneously by the PISH technique.
      CONCLUSION: Because PISH possesses high sensitivity for the detection of HPV
      infection in morphologically intact cells from uterine cervical neoplasia, the
      PISH technique might have promising potential for application to the detection of
      HPV presence in situ in screening.

PMID- 11531293
TI  - Expanded cytological referral criteria for colposcopy in cervical screening:
      comparison with human papillomavirus testing.
AB  - OBJECTIVE: The goal of this study was to investigate whether expanded cytologic
      referral criteria for colposcopy or the addition of human papillomavirus (HPV)
      testing on cervical screening could improve the rates of detection of cervical
      intraepithelial neoplasia (CIN). METHODS: HPV testing by semiquantitative
      polymerase chain reaction/ELISA was performed in 1000 women who were self
      referred for routine Pap smear. They underwent colposcopy following an abnormal
      smear result or a positive HPV test. As abnormal smear results were considered
      reports of low- or high-grade squamous intraepithelial lesion, atypical squamous
      cells of undetermined significance, and even HPV-associated reactive cellular
      changes (mild koilocytosis, mild dyskeratocytosis, hyperchromatic nuclei,
      bimultinucleation, and cleared cytoplasm). Loop excision of the transformation
      zone was performed in women with cytology and colposcopy indicative of CIN, as
      well as in women with normal cytology but positive HPV test and colposcopic
      impression of CIN. RESULTS: The Pap test was abnormal in 89% of the cases of CIN
      1 (34/38) and 96% of CIN 2/3 (27/28) diagnosed in our population. HPV testing
      picked up four additional cases of CIN 1 (11%) and one case of CIN 2/3 (4%).
      Overall the HPV test detected 95% of the cases of CIN 1 (36/38) and 89% of the
      cases of CIN 2/3 (25/28). CONCLUSION: HPV testing does not appear to add
      significantly to cytology in terms of positive predictive value or detection
      rate, if extended cytologic indications for colposcopy are used.

PMID- 11531294
TI  - Stamm gastrostomy for postoperative gastric decompression in gynecologic oncology
      patients.
AB  - OBJECTIVE: The aim of this study was to report our experience with Stamm
      gastrostomy for postoperative gastric decompression on a gynecologic oncology
      service. METHODS: This was an observational study over the 9-year period ending
      in October 2000. A 24 French MIC gastrostomy with the Stamm technique was used.
      Criteria for a gastrostomy are outlined in the text and tubes placed for
      palliation were excluded. Patients were followed to determine length of open
      drainage, time to removal, related complications, and those who may have
      benefited. RESULTS: A total of 167 patients had 174 nonpalliative gastrostomy
      tubes placed. Nine percent of the patients had related complications with a major
      complication rate of 2%. Overall, approximately one-third of the patients
      appeared to benefit from the gastrostomy tube. CONCLUSION: The results support
      the safety and efficacy of the MIC gastric tube in patients undergoing extensive
      gynecologic cancer surgery which is likely to impact the function of the
      gastrointestinal tract.

PMID- 11531295
TI  - Surgical blood loss in abdominal hysterectomy.
AB  - OBJECTIVE: The aim of this study was to evaluate additional error in estimating
      red cell loss during abdominal hysterectomy. METHODS: Eighty patients admitted
      consecutively for abdominal hysterectomy were recruited. The surgeries were done
      after heparinizing the suction tubing system to prevent clotting and reducing the
      vacuum pressure to reduce red cell lysis. At the end of the surgery, hematocrit
      was measured and compared with the patient's venous blood and the blood from the
      suction container. The Mann-Whitney test evaluated statistical significance.
      RESULTS: Eight patients were excluded for having a hemolyzed blood sample,
      receiving a blood transfusion, and having incomplete data. The study cohort
      consisted of 72 patients: 54 had a simple hysterectomy and 18 had a radical
      hysterectomy with pelvic and periaortic lymphadenectomy. The hematocrit (mean +/-
      standard deviation) in the suction container (19.8 +/- 8.8%) was lower than the
      hematocrit from the venous blood sample (32.4 +/- 6%) (P < 0.001). The hematocrit
      in the suction container decreased as the duration of the surgeries increased.
      Although the volume of blood in the suction container was used to estimate blood
      loss, the concentration of red cells in the container was consistently lower than
      those in the venous blood sample. The magnitude of dilution increased as the
      length and radical nature of the surgery increased. CONCLUSIONS: These findings
      suggest that other fluid, probably lymph, contributes to the dilution of red
      cells in the container and increases the estimated blood volume loss during
      surgery. Estimation of red cell surgical blood loss becomes less accurate as the
      length and radical nature of the surgery increase.

PMID- 11531296
TI  - Weekly intravenous methotrexate with folinic acid for nonmetastatic gestational
      trophoblastic neoplasia.
AB  - OBJECTIVE: The objective of this study was to determine the complete response
      rate to weekly intravenous methotrexate at 100 mg/m(2) with folinic acid for
      patients with nonmetastatic gestational trophoblastic neoplasia. METHODS: From
      1988 to 1999, 22 women with nonmetastatic gestational trophoblastic neoplasia
      were treated with weekly intravenous methotrexate with folinic acid at the
      Hamilton Regional Cancer Centre. Complete response was defined as the attainment
      of a serum beta-hCG level <5 IU/L for 3 consecutive weeks. Toxicity was graded
      according to the National Cancer Institute of Canada-Clinical Trials Group
      criteria for chemotherapy toxicity. RESULTS: There were 10 women who achieved
      complete response with weekly intravenous methotrexate alone (45.5%). Of the 12
      who did not achieve complete response with methotrexate, 10 received actinomycin
      D and 2 received EMA as second-line chemotherapy. Patients successfully treated
      with methotrexate required a median of 6.5 cycles (including 2 cycles for
      consolidation) to achieve complete response. The only significant prognostic
      factor for failure with methotrexate was pretreatment beta-hCG (P = 0.01).
      CONCLUSIONS: Only a select group of patients with low pretreatment beta-hCG
      titers would be expected to achieve complete response with this regimen. Large
      randomized studies are required to determine the optimal treatment for
      nonmetastatic gestational trophoblastic neoplasia.

PMID- 11531297
TI  - Long-term survival of intermediate risk endometrial cancer (stage IG3, IC, II)
      treated with full lymphadenectomy and brachytherapy without teletherapy.
AB  - OBJECTIVES: The aim of this study was to determine long-term survival and late
      complications of intermediate risk endometrial cancer (Stage IG3, IC, and II)
      treated with full lymphadenectomy and brachytherapy without teletherapy. METHODS:
      Two-hundred sixty-five consecutive patients underwent surgical staging for
      endometrial cancer consisting of hysterectomy, oophorectomy, and bilateral pelvic
      and periaortic lymphadenectomy. Sixty-six patients had intermediate risk
      endometrial cancer (Stage IG3, IC, and II) and received postoperative
      brachytherapy without teletherapy. Mean age was 68 years and mean weight was 188
      lb. Seventy-seven percent had associated medical illness. RESULTS: At a mean
      follow-up of 4.4 years, Kaplan-Meier estimated 5-year progression free survival
      is 97%. Two patients (3%) developed distant recurrence (abdomen, lungs) with no
      vaginal or pelvic recurrence. Major complications occurred in 6% of patients.
      CONCLUSIONS: Complete lymphadenectomy with brachytherapy without teletherapy for
      intermediate risk endometrial cancer results in excellent progression-free
      survival and minimal major morbidity.

PMID- 11531298
TI  - Nodal distribution and its significance in FIGO stage IIIc endometrial cancer.
AB  - OBJECTIVE: The aim of this study was to describe the distribution of nodal
      disease in FIGO Stage IIIc endometrial cancer (EC) and to evaluate whether nodal
      distribution is related to recurrence and survival. METHODS: Charts from EC
      patients with FIGO Stage IIIc disease from 1989 to 1998 were abstracted for
      clinicopathologic data, pelvic (PLN) and para-aortic (PALN) nodal involvement,
      number of positive/removed nodes, and extranodal disease spread. Patterns of
      nodal distribution were evaluated for site of first recurrence and survival.
      Associations between variables were tested by chi(2) and Wilcoxon rank sums.
      Survival analyses were performed by the Kaplan-Meier method. RESULTS: Of 607 EC
      patients evaluated, 47 were identified with FIGO Stage IIIc disease. All 47
      patients underwent hysterectomy and PLN sampling, and 42/47 had PALN sampling.
      The median number of PLN removed was 16 (range 2-35), and the median number of
      PALN was 7 (0-18). Stage IIIc disease was defined by positive PLN alone in 43%,
      positive PLN and PALN in 40%, and positive PALN alone in 17%. Positive peritoneal
      cytology and/or adnexal metastasis were present in 12 patients. Only 1/12 of
      these patients had isolated positive PLN whereas 11/12 had positive PALN (P =
      0.007). An increasing number of positive PLN was associated with PALN metastasis
      (P = 0.0001), and of the 10 patients with bilateral PLN involvement, 9/10 also
      had positive PALN (P = 0.001). Sites of first recurrence were similar regardless
      of whether PALN were positive. At a median follow-up of 37 months, the 3-year
      survival estimate was 70% for patients with positive PALN versus 87% for those
      with isolated PLN disease (P = 0.22). For all patients neither the total number
      of positive PLN nor the total number of PLN or PALN removed was associated with
      survival. CONCLUSIONS: PALN involvement is common in patients with FIGO Stage
      IIIc endometrial cancer, suggesting that PLN sampling alone may result in
      underdiagnosis of disease. Patients with positive PALN had more extensive
      disease, but survival and patterns of failure were not significantly different
      from those with disease confined to PLN, suggesting that lymph node dissection
      may have a therapeutic role.

PMID- 11531299
TI  - Primary malignant melanoma in ovarian cystic teratoma.
AB  - BACKGROUND: Malignant degeneration of benign cystic teratoma of the ovary is
      rare. Occurrence of melanoma in an ovarian cystic primary teratoma in the absence
      of a demonstrable extraovarian primary is even rarer. We describe here one such
      case. CASE: A 42-year-old nulliparous woman underwent laparotomy for a cyst in
      the right ovary. Histopathological examination of the specimen revealed malignant
      cystic teratoma with the presence of a melanoma component. There was no evidence
      of extraovarian primary melanoma on clinical examination. Two years later, she
      presented with lung metastasis and underwent left pneumonectomy. Histopathology
      confirmed metastatic melanoma. Postoperatively, she received combination
      chemotherapy using cisplatin and dacarbazine. She is on regular follow-up and
      continues to be disease-free, 18 months after treatment. CONCLUSION: Primary
      malignant melanoma in cystic teratoma of the ovary is extremely rare. We could
      find only 19 such cases on review of the literature. Clinical presentation is
      similar to that of primary epithelial ovarian cancer. Surgery remains the
      mainstay of treatment. Use of cisplatin and dacarbazine may be considered in a
      patient with metastatic disease.

PMID- 11531300
TI  - Endometrial stromal sarcoma: objective response to letrozole.
AB  - BACKGROUND: Low-grade endometrial stromal sarcoma is generally an indolent tumor
      rich in estrogen and progesterone receptors. Objective responses to hormonal
      therapy, most commonly with megestrol acetate, have been reported. CASE: The
      patient is a 51-year-old woman who presented with low-grade endometrial stromal
      sarcoma confined to the uterus in 1991 and was treated with total abdominal
      hysterectomy and bilateral salpingo-oophorectomy. Approximately 5 years later,
      the patient had recurrent pelvic disease treated with radiation therapy, followed
      by an attempt at resection. She was treated with megestrol acetate during the
      period she received radiation therapy with poor tolerance. Tamoxifen was then
      given with no tumor response. Megestrol acetate was restarted with progression of
      disease in the pelvis and abdomen. Letrozole was then given at a daily dose of
      2.5 mg with partial response for a duration of 9 months. CONCLUSION: Letrozole at
      a daily dose of 2.5 mg may be effective in low-grade endometrial stromal sarcoma
      with positive estrogen receptors.

PMID- 11531301
TI  - Hyperprolactinemia complicating juvenile granulosa cell tumor of the ovary.
AB  - BACKGROUND: Granulosa cell tumors are known to be hormonally active. They usually
      produce estrogen and inhibin, and the serum inhibin level is often considered a
      useful tumor marker during the follow-up of this illness. CASE: We present a case
      of malignant juvenile granulosa cell tumor associated with hyperprolactinemia. In
      our patient, the serum prolactin concentration closely reflected the behavior of
      the disease. CONCLUSION: Our findings are consistent with the assumption that
      prolactin was a tumor marker in this patient.

PMID- 11531302
TI  - Ovarian endodermal sinus tumor in a postmenopausal woman.
AB  - BACKGROUND: Ovarian endodermal sinus tumor is rare in postmenopausal women. CASE:
      We report the case of a 75-year-old woman with a pure endodermal sinus tumor of
      the ovary. CONCLUSION: We believe this to be the oldest patient reported with an
      ovarian endodermal sinus tumor. The histogenesis of this entity in older patients
      may be different than when it occurs in young women.

PMID- 11531303
TI  - Spontaneous regression of stage IV clear cell carcinoma of the endometrium in a
      patient with essential thrombocytosis.
AB  - OBJECTIVE: The aim of this study was to document a case of advanced stage clear
      cell carcinoma of the endometrium which underwent spontaneous regression (SR) and
      comment on the possible contribution of the patient's thrombocytosis. CASE
      REPORT: A 73-year-old woman with essential thrombocytosis presented with vaginal
      bleeding. Imaging demonstrated a complex uterine mass, a 4-cm infrarenal mass,
      and a 5-cm subumbilical mass. Biopsy of the subumbilical mass revealed
      adenocarcinoma, and endometrial curettage revealed extensively necrotic clear
      cell endometrial carcinoma. At hysterectomy 5 weeks later, the infrarenal and
      subumbilical masses were not identified. The endometrial tumor was almost
      completely necrotic. She received no adjuvant therapy and remains disease-free 6
      years later. Interestingly, her platelet-lowering agent (hydroxyurea) was
      discontinued shortly before, and her platelet count was significantly elevated at
      the time of her presentation with endometrial carcinoma. CONCLUSION: This report
      documents a rare case of SR of advanced endometrial carcinoma, and we speculate
      that increased circulating platelets were a major contributing factor.

PMID- 11531304
TI  - Epithelioid leiomyosarcoma of the uterine cervix.
AB  - BACKGROUND: Leiomyosarcomas with an epithelioid appearance arising in the uterine
      cervix are extremely rare neoplasms. We present a case of triple uterine cancer
      containing cervical epithelioid leiomyosarcoma. CASE: A 72-year-old Japanese
      woman, gravida 1, para 1, 55 years in menopause, visited her local doctor due to
      atypical bleeding and the endometrial smear was suspect for malignancy. She was
      referred to our hospital. Endometrial curettage revealed endometrioid
      adenocarcinoma, G1, with a fragment of sarcomatous tumor. A total hysterectomy
      with bilateral salpingo-oophorectomy was performed. The histological findings
      revealed triple uterine cancer consisting of endometrial adenocarcinoma, cervical
      epithelioid leiomyosarcoma, and cervical squamous cell carcinoma. CONCLUSION:
      This extremely rare case of triple uterine cancer containing cervical epithelioid
      leiomyosarcoma is the first report, to the best of our knowledge.

PMID- 11531305
TI  - Limited value of sonohysterography for endometrial screening in asymptomatic,
      postmenopausal patients treated with tamoxifen.

PMID- 11531307
TI  - Regarding Ng et al.: Defining the role of adjuvant radiotherapy for high-risk
      stage I endometrial patients.

PMID- 11531309
TI  - Chemotherapy in the treatment of locally advanced cervical cancer during
      pregnancy.

PMID- 11531312
TI  - Radical hysterectomy for early stage cervical cancer and resulting morbidity.

PMID- 11531313
TI  - Molecular epidemiological analysis of Salmonella enterica serotype Derby
      infections in Hong Kong.

PMID- 11531314
TI  - Meningococcal disease--some issues in treatment.

PMID- 11531315
TI  - Nucleic acid technologies and meningococcal infection.

PMID- 11531316
TI  - Dengue and other emerging flaviviruses.
AB  - Flaviviruses are among the most important emerging viruses known to man. Most are
      arboviruses (arthropod-borne) being transmitted by mosquitoes or ticks. They
      derived from a common ancestor 10-20000 years ago and are evolving rapidly to
      fill new ecological niches. Many are spreading to new geographical areas and
      causing increased numbers of infections. Traditionally, three clinical syndromes
      are recognized: fever-arthralgia-rash, viral haemorrhagic fever, and neurological
      disease, though for some flaviviruses the disease pattern is changing. Dengue,
      the most important flavivirus, is transmitted between humans by Aedes mosquitoes.
      Recent work is elucidating the pathogenesis of its most severe form, dengue
      haemorrhagic fever. Yellow fever, which has epidemiological similarities to
      dengue, was under control in the mid-20th century, but is once again increasing.
      Japanese encephalitis virus is numerically the most important cause of epidemic
      encephalitis; its geographical area is expanding despite the availability of
      vaccines. Other mosquito-borne neurotropic flaviviruses with clinical and
      epidemiological similarities are found across the globe. These include St Louis
      encephalitis virus, Murray Valley encephalitis virus, and West Nile virus, which
      recently reached the Americas for the first time. In cooler northern climates
      ticks are more important vectors. Tick-borne encephalitis virus occurs across
      large parts of Eastern Europe and the Commonwealth of Independent states. The
      tick-borne haemorrhagic flaviviruses, Omsk haemorrhagic fever and Kyasanur
      Forrest disease are localized in small areas.

PMID- 11531317
TI  - Prevalence of liver disease in patients with Streptococcus bovis bacteraemia.
AB  - BACKGROUND: The relationship between Streptococcus bovis bacteraemia and
      gastrointestinal disease (mainly colon cancer) is well known. Patients with
      advanced liver disease are prone to bacteraemia. Less attention has been paid to
      the association between liver disease and Streptococcus bovis bacteraemia in the
      literature. AIMS: To evaluate the prevalence of liver disease in patients with S.
      bovis bacteraemia. PATIENTS AND METHODS: Twenty-two episodes of S. bovis
      bacteraemia in 20 adults (13 males and seven females, with a median age of 61
      years, range 32-94 years) were detected in a single hospital over a 7-year
      period. Ten of them had endocarditis. Patients' clinical records were reviewed,
      with special focus on underlying liver and gastrointestinal disease. RESULTS:
      Eleven patients (55%) had a chronic liver disease. Nine of them were cirrhotics.
      Ten patients had a history of chronic alcohol abuse, and four patients had
      hepatitis C virus antibodies (associated with alcohol abuse in three cases).
      Large bowel disease was present in six out of 13 evaluable patients
      (adenocarcinoma in three cases). Patients with liver disease were younger than
      patients without it. Mortality related to S. bovis bacteraemia was particularly
      high among patients with advanced liver disease (Child-Pugh state C). Bacteraemia
      recurred two times in one alcoholic cirrhotic, who was diagnosed as having a
      Dukes-B colon cancer 4.5 years after the first episode of S. bovis bacteraemia.
      CONCLUSIONS: In our area, S. bovis bacteraemia is frequently associated with
      chronic liver disease. Liver disease may be a predisposing factor for S. bovis
      bacteraemia.

PMID- 11531318
TI  - Clinical characteristics and therapeutic outcome of patients with febrile
      neutropenia who present in shock: need for better strategies.
AB  - OBJECTIVE: To study the frequency of neutropenic febrile patients who present in
      shock, to evaluate the influence of this presenting feature on response to
      antibiotic therapy, morbidity, and mortality and to identify discriminating
      demographic features and clinical characteristics of these individuals. METHODS:
      Prospectively collected data on all episodes of fever and neutropenia observed in
      cancer patients who were hospitalized for parenteral antibiotic therapy. RESULTS:
      Five hundred and seventy-six patients were evaluated; 22 (3.8%) presented in
      shock. This group of individuals was compared with the remainder. Patients
      presenting in shock were more likely to be older (P< 0.01) and have progressive
      unresponsive cancer (P< 0.01). They were also more likely to present with septic
      appearance (P< 0.01), dehydration (P< 0.01), diarrhoea (P< 0.01), altered mental
      status (P< 0.01) clinical bleeding (P= 0.02) and dyspnoea (P< 0.01). They more
      often had anaemia (P< 0.01), thrombocytopenia (P= 0.02) and abnormal liver
      function tests (P< 0.01). Eight of the 22 patients presenting in shock had
      documented bacteraemia. Non-bacteraemic microbiological infections were observed
      in three patients. Five patients had clinical evidence of infection and another
      five were severely dehydrated and volume depleted. One patient had cardiogenic
      shock. Three patients were managed with monotherapy, 19 received combination
      antibiotics as initial empirical therapy. Overall outcome of these patients was
      extremely poor, particularly those with infectious aetiology. Eighteen (82%)
      patients expired. CONCLUSION: Neutropenic febrile patients who present in shock
      have extremely poor outcomes irrespective of type of initial antibiotic therapy.
      Intense efforts are required to improve their outcome.

PMID- 11531319
TI  - Antiretroviral therapy for HIV-2 infected patients.
AB  - OBJECTIVES: To evaluate clinical and RNA load response to antiretroviral therapy
      amongst patients infected with HIV-2 and to study the development of drug
      resistance. METHODS: Seven HIV-2 seropositive patients were monitored with
      clinical examination, CD4 cell count and HIV-2 viral RNA load. Viruses from four
      subjects were genotyped and in vitro recovery of virus by co-cultivation with
      PBMCs and HVS T-cells was attempted. Viruses isolated from two subjects were
      assayed for phenotypic antiviral resistance. The main outcome measures were the
      relationship between disease stage, viral load, CD4 cell count, viral subtype and
      the clinical course of HIV-2 infection and the effect of combination
      antiretroviral therapy on disease progression, CD4 cell count, HIV-2 RNA viral
      load and drug resistance. RESULTS: The median time of follow-up was 3 years
      (range 0-8 years). Three patients had AIDS, and one had symptomatic disease. Of
      the four patients genotyped, three were infected with HIV-2 subtype B and one
      with subtype A. Viraemia was detectable only at CD4 counts of less than 300 x
      10(6)/ml. Two patients with high viral loads failed to respond to antiretroviral
      therapy although their treatment may not have been optimal. One developed in
      vitro phenotypic antiviral resistance. The genotype of this patient's viral
      reverse transcriptase is being analysed. CONCLUSIONS: In contrast to HIV-1, HIV-2
      RNA levels were often undetectable despite advanced disease and low CD4 cell
      counts. However, HIV-2 was clearly capable of causing CD4 cell depletion
      resulting in symptomatic disease. The principles of highly active antiretroviral
      therapy seem to apply to HIV-2 and suboptimal therapy may lead to drug
      resistance. The timing of therapy initiation, monitoring of response and the
      measurement of resistance remain unresolved issues and conclusions cannot be
      extrapolated from HIV-1.

PMID- 11531320
TI  - The changing pattern of AIDS-defining illnesses with the introduction of highly
      active antiretroviral therapy (HAART)in a London clinic.
AB  - OBJECTIVES: To quantify the progressive impact of combination antiretroviral
      therapy (ART) on the incidence of AIDS-defining illnesses (ADIs) over a 9-year
      period. METHODS: Retrospective cohort study. Eligible patients were 1538 AIDS
      free, HIV-1-positive patients attending a large HIV clinic in west London who
      were at risk of developing AIDS because their CD4 count had declined to < or =350
      x 10(6)/l cells during the period 1 January 1990 and 31 December 1998. Incidence
      rates for the 12 most frequent ADIs were compared for two time periods, 1990-1995
      (pre-HAART) and 1996-1998 (post-HAART), using Poisson regression methods.
      Multivariate Poisson regression models were used to examine the contribution of
      ART and HAART to any observed temporal trends in incidence rates. RESULTS: After
      a median follow-up of 35 months, 450 (29%) patients had developed AIDS. Between
      the two time periods there was a significant decrease in the incidence of
      Pneumocystis carinii pneumonia (PCP) by 35% (4.11 per 100 person-years in 1990
      1995 vs. 2.67 in 1996-1998;P= 0.007), Kaposi's sarcoma by 34% (3.27 vs. 2.17;P=
      0.022) and cryptosporidiosis by 60% (0.76 vs. 0.31;P= 0.029). A non-significant
      reduction in incidence was observed for cryptococcosis by 45% (0.81 vs. 0.45;P=
      0.11), oesophageal candidiasis by 29% (3.34 vs. 2.39;P= 0.053) and mycobacterium
      avium complex by 18% (1.58 vs. 1.29;P= 0.4), and a non-significant increase was
      observed for tuberculosis by 17% (0.62 vs. 0.73;P= 0.66) and non-Hodgkins
      lymphoma (NHL) by 51% (0.43 vs. 0.65;P= 0.31). The incidence of cerebral
      toxoplasmosis, cytomegalovirus, recurrent bacterial chest infections and dementia
      remained stable. There was a clear stepwise reduction in the incidence of PCP,
      Kaposi's sarcoma and cryptosporidiosis with the use of non-H AART and HAART
      regimens relative to no ART. In a multivariate analysis, the use of ART and HAART
      explained the progressive decrease in incidence of PCP and Kaposi's sarcoma.
      CONCLUSIONS: The incidence of most ADIs has decreased over the last 9 years. The
      striking reduction in the inci-dence of PCP and Kaposi's sarcoma since 1996 can
      be attributed to the use of combination ART and particularly HAART. The non
      significant increase in the incidence of NHL and tuberculosis needs confirmation
      in other patient cohorts.

PMID- 11531321
TI  - Rapid serodiagnosis of gram-positive bacterial endocarditis.
AB  - OBJECTIVES: To characterize a serological test for diagnosing endocarditis caused
      by Gram-positive cocci. METHODS: We have developed an indirect enzyme-linked
      immunosorbent assay (ELISA) for the serological detection of Gram-positive
      infections. The test measures serum IgG directed towards lipid S, a recently
      identified exocellular glycolipid antigen which is related to lipoteichoic acid.
      We have previously shown the test to be of value in serodiagnosis of central
      venous catheter-associated sepsis and infection of orthopaedic prostheses caused
      by coagulase-negative staphylococci. We now describe the application of this test
      in endocarditis. RESULTS: Serum IgG levels to lipid S were significantly elevated
      in 34 patients with Gram-positive bacterial endocarditis confirmed as 'definite'
      by the Duke criteria as compared to 50 control patients. The test had a
      sensitivity of 88% and a specificity of 88%. CONCLUSIONS: The assay is
      independent of culture results or endocardial imaging, making it complementary to
      currently used investigations. It may therefore be possible to refine the current
      Duke criteria for diagnosing endocarditis. We describe an algorithm which
      incorporates lipid S serology into a positive diagnostic strategy.

PMID- 11531322
TI  - Molecular epidemiological analysis of Salmonella enterica serotype Derby
      infections in Hong Kong.
AB  - OBJECTIVES: We aimed to study the antimicrobial susceptibilities and molecular
      epidemiology of Salmonella enterica serotype Derby, a unique and common
      salmonella serotype in Hong Kong. METHODS: Salmonella Derby strains isolated from
      stools of patients in a large general hospital in Hong Kong from 1989 to 1994 and
      from food samples isolated in the Public Health Laboratory were randomly selected
      and investigated for the antimicrobial susceptibilities by determining the
      minimal inhibitory concentrations of 19 antimicrobial agents and their
      relatedness using plasmid analysis, ribotyping, pulsed-field gel electrophoresis
      (PFGE) and total DNA fingerprinting. RESULTS: About 50% of the 127 isolates
      studied were susceptible to all the 19 antibiotics tested, although resistance to
      tetracycline (49%) and sulfamethoxazole (38%) was high. Only 12% did not harbour
      any detectable plasmids, while the rest contained plasmids in 51 profiles. There
      were two predominant clones, one comprising of 35% of isolates that could not be
      pulsotyped because discrete bands were not discernible after PFGE and another
      comprising 34% of isolates that could be pulsotyped. The remaining 31% belonged
      to a variety of types. CONCLUSIONS: Approximately 70% of S. Derby belonging to
      two clones were endemic in the community, while the remaining isolates belonged
      to a variety of types which were probably a result of sporadic infection. The
      sources of human infections were foods, since most isolates from foods also
      belonged to the two endemic clones. Typing of S. Derby isolates from other
      sources such as animals or the environment would help elucidate how foods were
      contaminated. PFGE might not be universally applicable to all salmonella strains.

PMID- 11531323
TI  - Two cases of lymphadenopathy with liver dysfunction due to Mycoplasma pneumoniae
      infection with mycoplasmal bacteraemia without pneumonia.
AB  - We present two cases of unusual manifestations of Mycoplasma pneumoniae
      infection: lymphadenopathy with liver dysfunction without pneumonia. One was
      diagnosed as an infectious mononucleosis-like syndrome and the other as Kawasaki
      disease. Polymerase chain reaction successfully detected Mycoplasma pneumoniae
      DNA using blood samples. Mycoplasma pneumoniae can be included in the panel of
      aetiological agents in patients with lymphadenitis and hepatitis even in the
      absence of pneumonia.

PMID- 11531324
TI  - Hypercalcaemia and elevated 1,25(OH)(2)D(3) levels associated with disseminated
      Mycobacterium avium infection in AIDS.
AB  - Hypercalcaemia may complicate granulomatous diseases, such as tuberculosis and
      sarcoidosis, and various AIDS-related opportunistic infections and malignancies.
      We report here two patients with AIDS and disseminated Mycobacterium avium
      infection who developed symptomatic hypercalcaemia several weeks after commencing
      antimycobacterial chemotherapy, and in whom inappropriately elevated
      1,25(OH)(2)D(3)levels were documented. Although vitamin D supplementation may
      have contributed, no other cause for the hypercalcaemia was found. The
      biochemical and clinical similarities between these cases and other
      hypercalcaemic granulomatous diseases suggest a common mechanism related to
      macrophage activation and dysregulated vitamin D production.

PMID- 11531325
TI  - Diagnosis of Toxoplasma meningoencephalitis in a non-AIDS patient using PCR.
AB  - We report herein a rare case of Toxoplasma gondii meningoencephalitis in a non
      AIDS patient. Although T. gondii itself was not detected in nucleated cells in
      peripheral blood and cerebrospinal fluid under the microscope, the polymerase
      chain reaction method effectively detected the B1 gene of T. gondii in the cells.
      A serological examination showed increased levels of the IgG but not the IgM
      antibody to T. gondii, suggesting reactivation of the infection in the brain.

PMID- 11531326
TI  - Unusual presentation of typhoid fever: cutaneous vasculitis, pancreatitis, and
      splenic abscess.
AB  - We report a case of typhoid fever with an unusual presentation: prolonged fever
      with cutaneous vasculitis, pancreatitis, and splenic abscess. This is the first
      case of cutaneous leukocytoclastic vasculitis associated with Salmonella typhi.
      The diagnosis was made upon isolation of S. typhi in blood cultures, and after
      ruling out other causes of leukocytoclastic vasculitis. The outcome was
      favourable with antibiotics alone without surgery.

PMID- 11531327
TI  - Isolated renoureteric aspergilloma due to Aspergillus flavus: case report and
      review of the literature.
AB  - In this paper we describe a case in which acute renal colic was associated with
      elimination of multiple hyphal masses of Aspergillus flavus. Also, we reviewed
      the literature on similar cases and we found a similar pattern characterized by a
      marked male predominance, association with at least one underlying medical
      condition that predisposes to fungal infection, the presence of local symptoms
      resembling acute ureteral colic, and the absence of systemic manifestations.
      Moreover, our data suggest that Aspergillus balls must be suspected when a
      diabetic and intravenous drug user presents with acute renal colic and that non
      obstructive renal aspergillosis may be initially treated with itraconazole.

PMID- 11531328
TI  - Antiseptic treatment of methicillin-resistant Staphylococcus aureus
      conjunctivitis.

PMID- 11531329
TI  - Early prosthetic valve endocarditis due to Staphylococcus warneri with negative
      blood culture.

PMID- 11531330
TI  - Molecular characterisation of aureocin A70, a multi-peptide bacteriocin isolated
      from Staphylococcus aureus.
AB  - Staphylococcus aureus A70 produces a heat-stable bacteriocin designated aureocin
      A70. Aureocin A70 is encoded within a mobilisable 8 kb plasmid, pRJ6, and is
      active against Listeria monocytogenes. Experiments of transposition mutagenesis
      and gene cloning had shown that aureocin A70 production and immunity were
      associated with the HindIII-A and B fragments of pRJ6. Therefore, a 6332 bp
      region of the plasmid, encompassing both these fragments, was sequenced using a
      concatenation DNA sequencing procedure. DNA sequence and genetic analyses
      revealed the presence of three transcriptional units that appear to be involved
      in bacteriocin activity. The first transcriptional unit contains a single gene,
      aurT, which encodes a protein that resembles an ATP-dependent transporter,
      similar to those involved in lantibiotic export. AurT is required for aureocin
      A70 production and it appears to be essential for mobilisation of pRJ6. The
      second putative operon contains two open reading frames (ORFs); the first gene,
      orfA, is predicted to encode a protein similar to small repressor proteins found
      in some Archaea, whose function remains to be elucidated. The second gene, orfB,
      codes for an 138 amino acid residue protein which shares a number of
      characteristics (high pI and hydrophobicity profile) with proteins associated
      with immunity, needed for self-protection against bacteriocin. Four other genes
      are present in the third operon, aurABCD. aurABCD encode four related peptides
      that are small (30-31 amino acid residues), strongly cationic (pI of 9.85 to
      10.04) and highly hydrophobic. Theses peptides also have a high content of small
      amino acid residues like glycine and alanine, and no cysteine residue. Tn917-lac
      insertional mutations, which affected aureocin A70 activity, reside within operon
      aurABCD. Analysis of purified bacteriocin preparations by mass spectrometry
      demonstrated that all four peptides encoded by aurABCD operon are produced,
      expressed and excreted without post-translational modifications. Thus, aureocin
      A70 is a multi-peptide non-lantibiotic bacteriocin, which is transported without
      processing.

PMID- 11531331
TI  - The primase active site is on the outside of the hexameric bacteriophage T7 gene
      4 helicase-primase ring.
AB  - Gene 4 of bacteriophage T7 encodes a protein (gp4) that can translocate along
      single-stranded DNA, couple the unwinding of duplex DNA with the hydrolysis of
      dTTP, and catalyze the synthesis of short RNA oligoribonucleotides for use as
      primers by T7 DNA polymerase. Electron microscopic studies have shown that gp4
      forms hexameric rings, and X-ray crystal structures of the gp4 helicase domain
      and of the highly homologous RNA polymerase domain of Escherichia coli DnaG have
      been determined. Earlier biochemical studies have shown that when single-stranded
      DNA is bound to the hexameric ring, the primase domain remains accessible to free
      DNA. Given these results, a model was suggested in which the primase active site
      in the gp4 hexamer is located on the outside of the hexameric ring. We have used
      electron microscopy and single-particle image analysis to examine T7 gp4, and
      have determined that the primase active site is located on the outside of the
      hexameric ring, and therefore provide direct structural support for this model.

PMID- 11531332
TI  - The ribonuclease H activity of the reverse transcriptases of human
      immunodeficiency viruses type 1 and type 2 is affected by the thumb subdomain of
      the small protein subunits.
AB  - Retroviral reverse transcriptases (RTs) have both DNA polymerase and ribonuclease
      H (RNase H) activities. The RTs of HIV-1 and HIV-2 are heterodimers of p66/p51
      and p68/p54 subunits, respectively. The smaller subunit lacks the C-terminal
      segment of the larger subunit (which is the RNase H domain). The structure of the
      DNA polymerase domain of HIV-1 RT resembles a right hand (with fingers, palm and
      thumb subdomains), linked to the RNase H domain via the connection subdomain. The
      RNase H activity of the Rod strain of HIV-2 RT is about tenfold lower than that
      of HIV-1 RT, while the DNA polymerase activity of these RTs is similar. A
      chimeric RT in which residues 227-427 (which constitute a small part of the palm
      and the entire thumb and connection subdomains) of the Rod strain of HIV-2 RT
      were replaced by the corresponding segment from HIV-1 RT, has an RNase H activity
      as high as HIV-1 RT (despite the fact that the RNase H domain is derived from HIV
      2 RT). We analyzed the RNase H activity of wild-type HIV-2 RT from the D-194
      strain and compared it with this activity of the RT from the Rod strain of HIV-2
      and HIV-1 RT. The level of this activity of both HIV-2 RT strains was low;
      suggesting that low RNase H activity is a general property of HIV-2 isolates. The
      in vitro RNase H digestion pattern of the three wild-type RTs was
      indistinguishable, despite the difference in the level of RNase H activity. We
      constructed new chimeric HIV-1/HIV-2 RTs, in which protein segments and/or
      subunits were exchanged. The DNA polymerase activity of the parental HIV-1 and
      HIV-2 RTs was similar; as expected, the specific activity of the polymerases of
      all the hybrid RTs were also similar. However, the RNase H specific activity of
      the chimeric RTs was either high (like HIV-1 RT) or low (like HIV-2 RT). The
      origin of the thumb subdomain in the small subunit of the chimeric RTs (residues
      244-322) determines the level of the RNase H activity. The strand-transfer
      activity of the chimeric RTs is also affected by the thumb subdomain of the small
      subunit; transfer was much more efficient if this subdomain was derived from HIV
      1 RT. The data can be explained from the three-dimensional structure of HIV-1 RT.
      The thumb of the smaller subunit contacts the RNase H domain; it is through these
      contacts that the thumb affects the level of the RNase H activity of RT.

PMID- 11531333
TI  - Structure of the C-terminal RNA-binding domain of hnRNP D0 (AUF1), its
      interactions with RNA and DNA, and change in backbone dynamics upon complex
      formation with DNA.
AB  - Heterogeneous nuclear ribonucleoprotein (hnRNP) D0 has two ribonucleoprotein
      (RNP) -type RNA-binding domains (RBDs), each of which can specifically bind to
      the UUAG-sequence. hnRNP D0 also binds specifically to single-stranded
      d(TTAGGG)(n), the human telomeric DNA repeat. We have already reported the
      structure and interactions with RNA of the N-terminal RBD (RBD1). Here, the
      structure of the C-terminal RBD (RBD2) determined by NMR is presented. It folds
      into a compact alpha beta structure comprising an antiparallel beta-sheet packed
      against two alpha-helices, which is characteristic of RNP-type RBDs. In addition
      to the four beta-strands commonly found in RNP-type RBDs, an extra beta-strand,
      termed beta 4(-), was found just before the fourth beta-strand, yielding a five
      stranded beta-sheet. Candidate residues of RBD2 involved in the interactions with
      RNA were identified by chemical shift perturbation analysis. Perturbation was
      detected on the beta-sheet side, not on the opposite alpha-helix side, as
      observed for RBD1. It is notable that the beta 4(-) to beta 4 region of RBD2 is
      involved in the interactions in contrast to the case of RBD1. The chemical shift
      perturbation analysis also showed that RBD2 interacts with DNA in essentially the
      same way as with RNA. Changes in the backbone dynamics upon complex formation
      with DNA were examined by means of model free analysis of relaxation data. In
      free RBD2, the beta 4(-) to beta 4 region exhibits slow conformational exchange
      on the milli- to microsecond time scale. The exchange is quenched upon complex
      formation. The flexibility of free RBD2 may be utilized in the recognition
      process by allowing different conformational states to be accessed and
      facilitating induced fit. Additionally, faster flexibility on the nano- to
      picosecond time scale was observed for loop 3 located between beta 2 and beta 3
      in free RBD2, which is retained by the complex as well.

PMID- 11531334
TI  - Ribozyme catalysis via orbital steering.
AB  - Orbital steering is invoked to explain how the three-dimensional structure of a
      small self-cleaving RNA, the hammerhead ribozyme, both prevents and enhances RNA
      autocatalysis. Within the conserved catalytic core of the ribozyme, the position
      of the 2' oxygen atom of the G8 ribose is observed to be aligned almost perfectly
      with the phosphorus atom and the 5' oxygen atom of the adjacent A9 phosphate
      group for self-cleavage via an in-line attack mechanism. Despite this apparent
      near-perfect atomic positioning, no cleavage takes place. The explanation
      proposed is that a network of hydrogen bonds in the ribozyme core orients or
      steers the orbitals containing the electron lone pairs of the attacking
      nucleophile (the 2' oxygen atom) away from the A9 phosphorus atom, eliminating
      overlap with the vacant phosphorus d-orbitals despite the near-perfect in-line
      positioning of the oxygen atom, thus preventing catalysis. Because of the near
      perfect atomic positioning of the 2' oxygen atom relative to the phosphate group,
      orbital steering effects in this case are fortuitously uncoupled from
      conformational, distance and orientation effects, allowing an assessment of the
      catalytic power due purely to orbital steering. In contrast, a conformational
      change at the cleavage site is required to bring the 2' oxygen atom and the
      scissile phosphate group into atomic positions amenable to an in-line attack
      mechanism. In addition, the conformationally changed structure must then steer
      the lone-pair orbitals of the correctly positioned 2' oxygen atom toward the
      scissile phosphorus atom in order for cleavage to take place. We estimate that
      fulfillment of each of these two required changes may contribute separately an
      approximately 1000-fold rate enhancement, potentially accounting for a
      significant fraction of the catalytic power of this ribozyme. Orbital steering
      therefore appears to be a general phenomenon that may help to explain catalysis
      in both ribozymes and protein enzymes in a unified manner.

PMID- 11531335
TI  - Expression of the native cholera toxin B subunit gene and assembly as functional
      oligomers in transgenic tobacco chloroplasts.
AB  - The B subunits of enterotoxigenic Escherichia coli (LTB) and cholera toxin of
      Vibrio cholerae (CTB) are candidate vaccine antigens. Integration of an
      unmodified CTB-coding sequence into chloroplast genomes (up to 10,000 copies per
      cell), resulted in the accumulation of up to 4.1 % of total soluble tobacco leaf
      protein as functional oligomers (410-fold higher expression levels than that of
      the unmodified LTB gene expressed via the nuclear genome). However, expression
      levels reported are an underestimation of actual accumulation of CTB in
      transgenic chloroplasts, due to aggregation of the oligomeric forms in unboiled
      samples similar to the aggregation observed for purified bacterial antigen. PCR
      and Southern blot analyses confirmed stable integration of the CTB gene into the
      chloroplast genome. Western blot analysis showed that the chloroplast-
      synthesized CTB assembled into oligomers and were antigenically identical with
      purified native CTB. Also, binding assays confirmed that chloroplast-synthesized
      CTB binds to the intestinal membrane GM1-ganglioside receptor, indicating correct
      folding and disulfide bond formation of CTB pentamers within transgenic
      chloroplasts. In contrast to stunted nuclear transgenic plants, chloroplast
      transgenic plants were morphologically indistinguishable from untransformed
      plants, when CTB was constitutively expressed in chloroplasts. Introduced genes
      were inherited stably in subsequent generations, as confirmed by PCR and Southern
      blot analyses. Increased production of an efficient transmucosal carrier molecule
      and delivery system, like CTB, in transgenic chloroplasts makes plant-based oral
      vaccines and fusion proteins with CTB needing oral administration commercially
      feasible. Successful expression of foreign genes in transgenic chromoplasts and
      availability of marker-free chloroplast transformation techniques augurs well for
      development of vaccines in edible parts of transgenic plants. Furthermore, since
      the quaternary structure of many proteins is essential for their function, this
      investigation demonstrates the potential for other foreign multimeric proteins to
      be properly expressed and assembled in transgenic chloroplasts.

PMID- 11531336
TI  - Activation of preformed EGF receptor dimers by ligand-induced rotation of the
      transmembrane domain.
AB  - The epidermal growth factor receptor plays crucial roles throughout the
      development of multicellular organisms, and inappropriate activation of the
      receptor is associated with neoplastic transformation of many cell types. The
      receptor is thought to be activated by ligand-induced homodimerisation. Here,
      however, we show by chemical cross-linking and sucrose density-gradient
      centrifugation that in the absence of bound ligand the receptor has an ability to
      form a dimer and exists as a preformed dimer on the cell surface. We also
      analysed the receptor dimerisation by inserting cysteine residues at strategic
      positions about the putative alpha-helix axis of the extracellular juxtamembrane
      region. The mutant receptors spontaneously formed disulphide bridges and
      transformed NIH3T3 cells in the absence of ligand, depending upon the positions
      of the cysteine residue inserted. Kinetic analyses of the disulphide bonding
      indicate that EGF binding induces flexible rotation or twist of the juxtamembrane
      region of the receptor in the plane parallel with the lipid bilayer. The binding
      of an ATP competitor to the intracellular domain also induced similar flexible
      rotation of the juxtamembrane region. All the disulphide-bonded dimers had
      flexible ligand-binding domains with the same biphasic affinities for EGF as the
      wild-type. These results demonstrate that ligand binding to the flexible
      extracellular domains of the receptor dimer induce rotation or twist of the
      juxtamembrane regions, hence the transmembrane domains, and dissociate the
      dimeric, inactive form of the intracellular domains. The flexible rotation of the
      intracellular domains may be necessary for the intrinsic catalytic kinase to
      become accessible to the multiple tyrosine residues present in the regulatory
      domain and various substrates, and may be a common property of many cell-surface
      receptors, such as the insulin receptor.

PMID- 11531337
TI  - Crossbridge and tropomyosin positions observed in native, interacting thick and
      thin filaments.
AB  - Tropomyosin movements on thin filaments are thought to sterically regulate muscle
      contraction, but have not been visualized during active filament sliding. In
      addition, although 3-D visualization of myosin crossbridges has been possible in
      rigor, it has been difficult for thick filaments actively interacting with thin
      filaments. In the current study, using three-dimensional reconstruction of
      electron micrographs of interacting filaments, we have been able to resolve not
      only tropomyosin, but also the docking sites for weak and strongly bound
      crossbridges on thin filaments. In relaxing conditions, tropomyosin was observed
      on the outer domain of actin, and thin filament interactions with thick filaments
      were rare. In contracting conditions, tropomyosin had moved to the inner domain
      of actin, and extra density, reflecting weakly bound, cycling myosin heads, was
      also detected, on the extreme periphery of actin. In rigor conditions,
      tropomyosin had moved further on to the inner domain of actin, and strongly bound
      myosin heads were now observed over the junction of the inner and outer domains.
      We conclude (1) that tropomyosin movements consistent with the steric model of
      muscle contraction occur in interacting thick and thin filaments, (2) that myosin
      induced movement of tropomyosin in activated filaments requires strongly bound
      crossbridges, and (3) that crossbridges are bound to the periphery of actin, at a
      site distinct from the strong myosin binding site, at an early stage of the
      crossbridge cycle.

PMID- 11531338
TI  - Structure of the soluble domain of a membrane-anchored thioredoxin-like protein
      from Bradyrhizobium japonicum reveals unusual properties.
AB  - TlpA is an unusual thioredoxin-like protein present in the nitrogen-fixing soil
      bacterium Bradyrhizobium japonicum. A hydrophobic N-terminal transmembrane domain
      anchors it to the cytoplasmic membrane, whereby the hydrophilic thioredoxin
      domain becomes exposed to the periplasmic space. There, TlpA catalyses an
      essential reaction, probably a reduction, in the biogenesis of cytochrome aa(3).
      The soluble thioredoxin domain (TlpA(sol)), devoid of the membrane anchor, was
      purified and crystallized. Oxidized TlpA(sol) crystallized as a non-covalent
      dimer in the space group P2(1)2(1)2(1). The X-ray structure analysis was carried
      out by isomorphous replacement using a xenon derivative. This resulted in a high
      resolution (1.6 A) three-dimensional structure that displayed all of the features
      of a classical thioredoxin fold. A number of peculiar structural details were
      uncovered: (i) Only one of the two active-site-cysteine sulphurs (Cys72, the one
      closer to the N terminus) is exposed on the surface, making it the likely
      nucleophile for the reduction of target proteins. (ii) TlpA(sol) possesses a
      unique structural disulphide bond, formed between Cys10 and Cys155, which
      connects an unprecedented N-terminal alpha helix with a beta sheet near the C
      terminus. (iii) An insertion of about 25 amino acid residues, not found in the
      thioredoxin prototype of Escherichia coli, contributes only marginally to the
      thioredoxin fold, but forms an extra, surface-exposed alpha helix. This region
      plus another surface-exposed stretch (-Ile-Gly-Arg-Ala-), which is absent even in
      the closest TlpA relatives, might be considered as specificity determinants for
      the recognition of target proteins in the periplasm. The TlpA(sol) structure
      paves the way towards unraveling important structure-function relationships by
      rational mutagenesis.

PMID- 11531339
TI  - The analysis of the human high affinity IgE receptor Fc epsilon Ri alpha from
      multiple crystal forms.
AB  - We have solved the structure of the human high affinity IgE receptor, Fc epsilon
      RI alpha, in six different crystal forms, showing the structure in 15 different
      chemical environments. This database of structures shows no change in the overall
      shape of the molecule, as the angle between domains 1 and 2 (D1 and D2) varies
      little across the ensemble. However, the receptor has local conformational
      variability in the C' strand of D2 and in the BC loop of D1. In every crystal
      form, a residue inserts between tryptophan residues 87 and 110, mimicking the
      position of a proline from the IgE ligand. The different crystal forms reveal a
      distribution of carbohydrates lining the front and back surfaces of the
      structure. An analysis of crystal contacts in the different forms indicates
      regions where the molecule interacts with other proteins, and reveals a potential
      new binding site distal to the IgE binding site. The results of this study point
      to new directions for the design of molecules to inhibit the interaction of Fc
      epsilon RI alpha with its natural ligand and thus to prevent a primary step in
      the allergic response.

PMID- 11531340
TI  - V-shaped scaffold: a new architectural motif identified in an A x (G x G x G x G)
      pentad-containing dimeric DNA quadruplex involving stacked G(anti) x G(anti) x
      G(anti) x G(syn) tetrads.
AB  - We report the results of an NMR study of unlabeled and uniformly (13)C,(15)N
      labeled d(G(3)AG(2)T(3)G(3)AT) in 100 mM NaCl, conditions under which it forms a
      dimeric quadruplex containing several new topological features. The DNA oligomer
      chain in each symmetry-related monomer subunit undergoes three sharp turns to
      form a compact domain, with all the purine bases involved in pairing alignments.
      The first turn is of the double chain reversal type, the second is of the
      edgewise type, and the third represents a new alignment, the V-shaped type. Each
      monomer of the dimeric quadruplex contains two stacked G(anti) x G(anti) x
      G(anti) x G(syn) tetrads, one of which forms a newly identified A x (G x G x G x
      G) pentad, through sheared G.A mismatch formation. There is a break in one of the
      four G-G columns that link adjacent G x G x G x G tetrads within each monomer.
      This architectural interruption is compensated by a new topological feature of
      quadruplex architecture, the V-shaped scaffold. The missing G-G column results in
      an opening that could facilitate insertion of planar ligands into the quadruplex.
      The dimeric interface contains stacked A.(G.G.G.G) pentads, with each pentad
      containing four bases from one monomer and a syn G1 from the partner monomer.
      Several potential ligand-binding pockets, positioned towards either end of the
      folded architecture, were identifiable in a surface view of the solution
      structure of the dimeric d(G(3)AG(2)T(3)G(3)AT) quadruplex.

PMID- 11531341
TI  - D(n)-symmetrical tertiary templates for the design of tubular proteins.
AB  - Antiparallel helical bundles are found in a wide range of proteins. Often, four
      helical bundles form tube-like structures, with binding sites for substrates or
      cofactors near their centers. For example, a transmembrane four-helical bundle in
      cytochrome bc(1) binds a pair of porphyrins in an elongated central cavity
      running down the center of the structure. Antiparallel helical barrels with
      larger diameters are found in the crystal structures of TolC and DSD, which form
      antiparallel 12-helical and six-helical bundles, respectively. The backbone
      geometries of the helical bundles of cytochrome bc(1), TolC, and DSD are well
      described using a simple D(n)-symmetrical model with only eight adjustable
      parameters. This parameterization provides an excellent starting point for
      construction of minimal models of these proteins as well as the de novo design of
      proteins with novel functions.

PMID- 11531342
TI  - Denatured state thermodynamics: residual structure, chain stiffness and scaling
      factors.
AB  - A set of nine variants of yeast iso-1-cytochrome c with zero or one surface
      histidine have been engineered such that the N-terminal amino group is acetylated
      in vivo. N-terminal acetylation has been confirmed by mass spectral analysis of
      intact and proteolytically digested protein. The histidine-heme loop-forming
      equilibrium, under denaturing conditions (3 M guanidine hydrochloride), has been
      measured by pH titration providing an observed pK(a), pK(a)(obs), for each
      variant. N-terminal acetylation prevents the N-terminal amino group-heme binding
      equilibrium from interfering with measurements of histidine-heme affinity.
      Significant deviation is observed from the linear dependence of pK(a)(obs) on the
      log of the number of monomers in the loop formed, expected for a random coil
      denatured state. The maximum histidine-heme affinity occurs for a loop size of 37
      monomers. For loop sizes of 37-83 monomers, histidine-heme pK(a)(obs) values are
      consistent with a scaling factor of -4.2+/-0.3. This value is much larger than
      the scaling factor of -1.5 for a freely jointed random coil, which is commonly
      used to represent the conformational properties of protein denatured states. For
      loop sizes of nine to 22 monomers, chain stiffness is likely responsible for the
      decreases in histidine-heme affinity relative to a loop size of 37. The results
      are discussed in terms of residual structure and sequence composition effects on
      the conformational properties of the denatured states of proteins.

PMID- 11531343
TI  - High-resolution 1H NMR spectroscopy in the solid state: very fast sample rotation
      and multiple-quantum coherences.
AB  - In the past few years, solid-state 1H NMR spectroscopy under fast magic-angle
      spinning (MAS) has developed into a versatile tool for elucidating structure and
      dynamics. Dipolar multiple-quantum (MQ), in particular double-quantum (DQ), MAS
      spectroscopy has been applied to a variety of materials and provided unique
      insight, e.g., into the structure of hydrogen-bonded systems. This review intends
      to present solid-state 1H DQ and MQ MAS spectroscopy in a systematic fashion with
      a particular emphasis on methodological aspects, followed by an overview of
      applications.

PMID- 11531345
TI  - Phosphorus-31 solid-state nmr in high-field gradients: prospects for imaging bone
      using the long echo-train summation technique (LETS).
AB  - Stray-field techniques are reported for 31P studies of solids for a variety of
      compounds including bone, bone meal and calcium hydroxyapatite. Long Hahn echo
      trains produced by the application of many pulses were used as in the long echo
      train summation technique. Double-resonance enhancements of 31P by use of both
      direct and indirect experiments were attempted on a sample of NH4PF6:31P[19F]
      double resonance produced, at most, a 26% increase in the initial level of the
      31P echo signal.

PMID- 11531346
TI  - Measurement of homonuclear proton couplings based on cross-peak nulling in CT
      COSY.
AB  - A method in which 1H-1H scalar and dipolar couplings are obtained from the cross
      peak nulling condition in a series of constant-time (CT) COSY spectra, as a
      function of the duration of the CT period, is described. The method is best
      suited for measurement of 1H-1H couplings in the range 5-20 Hz. It is shown,
      however, that results can be sensitive to cross-correlated relaxation effects.
      Also, artifactual resonances, resulting from strong coupling, can be quite
      pronounced in CT-COSY spectra, even when /J(AB)/(deltaA-deltaB)/<0.1. The
      experiments are demonstrated for the DNA dodecamer d(CGCGAATTCGCG)2, both in
      isotropic solution and in a liquid crystalline phase.

PMID- 11531347
TI  - Investigating magnetically aligned phospholipid bilayers with EPR spectroscopy at
      94 GHz.
AB  - In this paper, we report our initial results on studying magnetically aligned
      phospholipid bilayers (bicelles) at high magnetic fields (approximately 3.4 T)
      with electron paramagnetic resonance (EPR) spectroscopy at 95 GHz (W-band). In
      order to characterize this system for W-band EPR studies, we have utilized the
      nitroxide spin probe 3beta-doxyl-5alpha-cholestane to demonstrate the effects of
      macroscopic bilayer alignment. At W-band due to the increase in magnetic field
      strength (when compared to X-band studies at 9.5 GHz) (S. M. Garber et al., J.
      Am. Chem. Soc. 121, 3240-3241 (1999)), we were able to examine magnetically
      aligned phospholipid bilayers at two orientations with the bilayer normal
      oriented either perpendicular or parallel (upon addition of YbCl3) with respect
      to the direction of the static magnetic field. Additionally, at a magnetic field
      of 3.4 T (g=2 resonance at W-band), we were able to study the parallel alignment
      with a lower concentration of Yb3+, thereby eliminating the possible unwanted
      effects associated with lanthanide-protein interactions and paramagnetic shifts
      and/or line broadening induced by the lanthanide ions. The development of this
      new spin label alignment technique will open up a whole new area of investigation
      for phospholipid bilayer systems and membrane protein EPR studies at high
      magnetic fields.

PMID- 11531352
TI  - Dynamics of spin I=3/2 under spin-locking conditions in an ordered environment.
AB  - We have derived approximate analytic solutions to the master equation describing
      the evolution of the spin I=3/2 density operator in the presence of a radio
      frequency (RF) field and both static and fluctuating quadrupolar interactions.
      Spectra resulting from Fourier transformation of the evolutions of the on
      resonance spin-locked magnetization into the various coherences display two
      satellite pairs and, in some cases, a central line. The central line is generally
      trimodal, consisting of a narrow component related to a slowly relaxing mode and
      two broad components pertaining to two faster relaxing modes. The rates of the
      fast modes are sensitive to slow molecular motion. Neither the amplitude nor the
      width of the narrow component is affected by the magnitude of the static
      coupling, whereas the corresponding features of the broad components depend in a
      rather complicated manner on the spin-lock field strength and static quadrupolar
      interaction. Under certain experimental conditions, the dependencies of the
      amplitudes on the dynamics are seen to vanish and the relaxation rates reduce to
      relatively simple expressions. One of the promising emerging features is the fact
      that the evolutions into the selectively detected quadrupolar spin polarization
      order and the rank-two double-quantum coherence do not exhibit a slowly relaxing
      mode and are particularly sensitive to slow molecular motion. Furthermore, these
      coherences can only be excited in the presence of a static coupling and this
      makes it possible to discern nuclei in anisotropic from those in isotropic
      environment. The feasibility of the spin-lock pulse sequences with limited RF
      power and a nonvanishing average electric field gradient has been demonstrated
      through experiments on sodium in a dense lyotropic DNA liquid crystal.

PMID- 11531353
TI  - Linewidth-resolved 15N HSQC, a simple 3D method to measure 15N relaxation times
      from T1 and T2 linewidths.
AB  - A three-dimensional approach for measuring 15N relaxation times is described.
      Instead of selecting particular values for the relaxation period, in the proposed
      method the relaxation period is incremented periodically in order to create a 3D
      spectrum. This additional frequency domain of the transformed spectrum contains
      the relaxation time information in the T1 and T2 linewidths, and thus the
      longitudinal and transverse 15N relaxation times can be measured without
      determination of 2D cross peak volumes/intensities and subsequent curve fitting
      procedures.

PMID- 11531355
TI  - Sequential HNCACB and CBCANH protein NMR pulse sequences.
AB  - The pulse sequences HNCACB and CBCANH correlating side chain C(beta) resonances
      with amide resonances in the protein backbone do not distinguish between inter-
      and intraresidue correlations. The new pulse sequences sequential HNCACB and
      sequential CBCANH make this distinction by suppressing coherence transfer between
      13C(alpha) and 15N via the one-bond J(NC(alpha)) coupling so that only the
      sequential correlations are observed in the spectrum. The experimental results of
      applying sequential HNCACB in a clean-TROSY-adapted implementation to the protein
      Chymotrypsin Inhibitor 2 at 800 MHz are presented.

PMID- 11531354
TI  - 1H-1H MAS correlation spectroscopy and distance measurements in a deuterated
      peptide.
AB  - In this Communication, we demonstrate the use of deuteration together with back
      substitution of exchangeable protons as a means of attenuating the strong 1H-1H
      couplings that broaden 1H magic angle spinning (MAS) spectra of solids. The
      approach facilitates 15N-1H correlation experiments as well as experiments for
      the measurement of 1H-1H distances. The distance measurement relies on the
      excellent resolution in the 1H MAS spectrum and homonuclear double quantum
      recoupling techniques. The 1H-1H dipolar recoupling can be analyzed in an
      analytical fashion by fitting the data to a 2- or 3-spin system. The experiments
      are performed on a sample of the dipeptide N-Ac-Val-Leu-OH, which was synthesized
      from uniformly [2H, 15N] labeled materials and back-exchanged in H2O.

PMID- 11531356
TI  - Accurate measurement of small spin-spin couplings in partially aligned molecules
      using a novel J-mismatch compensated spin-state-selection filter.
AB  - The accurate measurement of small spin-spin coupling constants in macromolecules
      dissolved in a liquid crystalline phase is important in the context of molecular
      structure investigation by modern liquid state NMR. A new spin-state-selection
      filter, DIPSAP, is presented with significantly reduced sensitivity to J-mismatch
      of the filter delays compared to previously proposed pulse sequences. DIPSAP
      presents an attractive new approach for the accurate measurement of small spin
      spin coupling constants in molecules dissolved in anisotropic solution.
      Application to the measurement of 15N-13C' and 1H(N)-13C' coupling constants in
      the peptide planes of 13C, 15N labeled proteins demonstrates the high accuracy
      obtained by a DIPSAP-based experiment.

PMID- 11531357
TI  - Measuring the longitudinal NMR relaxation rates of fast relaxing nuclei using a
      signal eliminating relaxation filter.
AB  - A new experiment for selective determination of the relaxation rates of fast
      relaxing NMR signals is presented. The experiment is derived from the
      conventional inversion recovery experiment by substituting the 180 degrees
      inversion pulse of this experiment with a signal eliminating relaxation filter
      (SERF) consisting of three 180 degrees pulses separated by two variable delays,
      Delta1 and Delta2. The SERF experiment allows a selective suppression of signals
      with relaxation rates below a given limit while monitoring the relaxation of
      faster relaxing signals. The experiment was tested on a sample of 20% oxidized
      plastocyanin from Anabaena variabilis, where the fast exchange of an electron
      between the reduced (diamagnetic) and the oxidized (paramagnetic) form results in
      a series of average signals with widely different relaxation rates. To ensure an
      optimum extraction of information from the experimental data, the relaxation
      rates were obtained from the SERF experiment by a simultaneous analysis of all
      the FIDs of the experiment using a fast linear prediction model method developed
      previously. The reliability of the relaxation rates obtained from the SERF
      experiment was confirmed by a comparison of the rates with the corresponding
      rates obtained from a conventional inversion recovery experiment.

PMID- 11531358
TI  - Measurement of interfluorine distances in solids.
AB  - (19)F homonuclear dipolar recoupling methods were used to measure internuclear
      distances ranging from 5 to 12 A in fluorinated organic compounds in the solid
      state. Magic-angle-spinning-based high-resolution techniques were utilized.
      Trifluoromethyl and aromatic fluorine groups were separated by rigid aromatic
      spacers; these compounds were diluted into nonfluorinated host molecule matrices
      to give isolated homonuclear spin pairs with known internuclear distances.
      Radiofrequency-driven recoupling (RFDR) was used to elicit magnetization exchange
      between the spin pairs in 1D and 2D experiments. Simulation of the exchange was
      accomplished using a Monte Carlo-type algorithm to search the parameter space.
      These methods allow the determination of distances with an accuracy of 1 A at
      shorter distances and 2 A at longer distances, with the assumption of no prior
      knowledge of T(2)(ZQ).

PMID- 11531359
TI  - A novel dipolar dephasing method for the slow magic angle turning experiment.
AB  - Complete suppression of the resonances from protonated carbons in a slow magic
      angle spinning experiment can be achieved using five dipolar dephasing (Five-DD)
      periods distributed in one rotor period. This produces a spectrum containing only
      the spinning sidebands (SSB) from the nonprotonated carbons. It is shown that the
      SSB patterns corresponding to the nonprotonated carbons are not distorted over a
      wide range of dipolar dephasing times. Hence, this method can be used to obtain
      reliable principal values of the chemical shift tensors for each nonprotonated
      carbon. The Five-DD method can be readily incorporated into isotropic-anisotropic
      2D experiments such as FIREMAT and 2D-PASS to facilitate the measurement of the
      (13)C chemical shift tensors in complex systems.

PMID- 11531360
TI  - Double-quantum-filtered rotational-resonance MAS NMR in the presence of large
      chemical shielding anisotropies.
AB  - Double-quantum filtration under rotational resonance MAS NMR conditions where the
      chemical shielding anisotropies involved exceed the differences in isotropic
      chemical shielding is considered by means of numerical simulations and (13)C MAS
      NMR experiments. The responses of two different pulse sequences, suitable for
      double-quantum filtration specifically under rotational resonance conditions, to
      large chemical shielding anisotropies are compared. In the presence of large
      chemical shielding anisotropies a very recently introduced pulse sequence (T.
      Karlsson, M. Eden, H. Luthman, and M. H. Levitt, J. Magn. Reson. 145, 95-107,
      2000) suffers losses in double-quantum-filtration efficiencies. The double
      quantum-filtration efficiency of another pulse sequence (N. C. Nielsen, F.
      Creuzet, R. G. Griffin, and M. H. Levitt, J. Chem. Phys. 96, 5668-5677, 1992) is
      less afflicted by the presence of large chemical shielding anisotropies. Both
      sequences deliver double-quantum-filtered lineshapes that sensitively reflect
      chemical shielding tensor orientations. It is further shown that double-quantum
      filtered rotational-resonance lineshapes of spin systems composed of more than
      two spins offer a suitable experimental approach for determining chemical
      shielding tensor orientations for cases where conventional rotational-resonance
      experiments are not applicable due to the presence of additional background
      resonances.

PMID- 11531361
TI  - The filtering approach to solvent peak suppression in MRS: a critical review.
AB  - Suppressing the solvent peak is important in many applications of biomedical NMR
      spectroscopy in order to quantify the metabolites with a great accuracy. Among
      the postprocessing methods proposed in the literature, many deal with the concept
      of filtering. However, several proposals lack a theoretical perspective and some
      have not been explicitly applied to quantification problems. The present article
      is intended to bridge this gap: five methods are analyzed from a theoretical
      perspective. Subsequently the different methods are applied to the same set of
      data, and then the latter are quantified using the model fitting method AMARES.
      With our set, the scheme proposed by T. Sundin et al. (J. Magn. Reson. 139(2),
      189-204 (1999)) proved to be the most reliable method.

PMID- 11531362
TI  - Analytical computation of the eigenvalues and eigenvectors in DT-MRI.
AB  - In this paper a noniterative algorithm to be used for the analytical
      determination of the sorted eigenvalues and corresponding orthonormalized
      eigenvectors obtained by diffusion tensor magnetic resonance imaging (DT-MRI) is
      described. The algorithm uses the three invariants of the raw water spin self
      diffusion tensor represented by a 3 x 3 positive definite matrix and certain math
      functions that do not require iteration. The implementation requires a positive
      definite mask to preserve the physical meaning of the eigenvalues. This algorithm
      can increase the speed of eigenvalue/eigenvector calculations by a factor of 5-40
      over standard iterative Jacobi or singular-value decomposition techniques. This
      approach may accelerate the computation of eigenvalues, eigenvalue-dependent
      metrics, and eigenvectors especially when having high-resolution measurements
      with large numbers of slices and large fields of view.

PMID- 11531363
TI  - Pure-phase selective excitation in fast-relaxing systems.
AB  - Selective pulses have been used frequently for small molecules. However, their
      application to proteins and other macromolecules has been limited. The long
      duration of shaped-selective pulses and the short T(2) relaxation times in
      proteins often prohibited the use of highly selective pulses especially on larger
      biomolecules. A very selective excitation can be obtained within a short time by
      using the selective excitation sequence presented in this paper. Instead of using
      a shaped low-intensity radiofrequency pulse, a cluster of hard 90 degrees pulses,
      delays of free precession, and pulsed field gradients can be used to selectively
      excite a narrow chemical shift range within a relatively short time. Thereby, off
      resonance magnetization, which is allowed to evolve freely during the free
      precession intervals, is destroyed by the gradient pulses. Off-resonance
      excitation artifacts can be removed by random variation of the interpulse delays.
      This leads to an excitation profile with selectivity as well as phase and
      relaxation behavior superior to that of commonly used shaped-selective pulses.
      Since the evolution of scalar coupling is inherently suppressed during the double
      selective excitation of two different scalar-coupled nuclei, the presented pulse
      cluster is especially suited for simultaneous highly selective excitation of N-H
      and C-H fragments. Experimental examples are demonstrated on hen egg white
      lysozyme (14 kD) and the bacterial antidote ParD (19 kD).

PMID- 11531364
TI  - Nonparametric NMR spectroscopy.
AB  - The parametric (or model-based) approach to NMR spectroscopy suffers from two
      general problems: it is sensitive to modeling errors and requires knowledge of
      the number of resonances present in the compound(s) under analysis. The
      nonparametric approach has neither of these drawbacks and it may also be
      computationally simpler than the parametric approach. However, if not applied
      properly, the nonparametric approach may yield significantly less accurate
      spectroscopic results than the parametric approach. In this paper we introduce a
      high-resolution nonparametric methodology for NMR spectroscopy based on the
      adaptive filter bank approach. The main salient feature of the new approach is
      that it provides 2D spectra versus both frequency and damping, as opposed to the
      classical 1D frequency spectra routinely used in NMR spectroscopy. To show the
      power of our new nonparametric approach we compare its performance with the
      ultimate performance of the parametric approach. We use both simulated and real
      NMR signals in our numerical performance study.

PMID- 11531365
TI  - Triple-quantum-filtered (23)Na NMR spectroscopy of subcutaneously implanted 9l
      gliosarcoma in the rat in the presence of TmDOTP(5-1).
AB  - The utility of triple-quantum (TQ)-filtered (23)Na NMR spectroscopy for
      discriminating between intra- and extracellular Na(+)(Na(i)(+) and Na(e)(+),
      respectively) in a solid tumor in vivo was evaluated using TmDOTP(5-) as a (23)Na
      shift reagent. Infusion of 80 mM TmDOTP(5-) without added Ca(2+) produced
      baseline-resolved Na(i)(+) and Na(e)(+) peaks in both single-quantum (SQ) and TQ
      filtered (23)Na spectra. The Na(i)(+) signal represented 22+/-4% of the SQ
      spectrum, but 59+/-10% of the TQ-filtered spectrum. Therefore, the Na(i)(+)
      contribution in TQ-filtered spectra is much higher than in SQ spectra. Both SQ
      and TQ-filtered Na(i)(+) signals increased by about 75% 1 h after sacrificing the
      animal. The TQ-filtered relaxation times did not change during this time,
      indicating that changes observed in TQ-filtered spectra collected with a
      preparation time of 3 ms represent changes in the concentration of sodium ions
      contributing to the TQ-filtered signal. Similar experiments were conducted
      without TmDOTP(5-) to determine changes in the Na(e)(+) signal in the absence of
      the shift reagent. The changes in total SQ and TQ-filtered signals 1 h after
      sacrificing the animal showed that the SQ Na(e)(+) signal decreased by
      approximately 35%, while the TQ-filtered Na(e)(+) signal did not change
      significantly. This demonstrates that the TQ-filtered (23)Na signal is relatively
      insensitive to changes in Na(e)(+) content. To our knowledge, this work
      represents the first evaluation of multiple-quantum-filtered (23)Na spectroscopy
      to discriminate between intra- and extracellular Na(+) in a solid tumor in vivo.

PMID- 11531366
TI  - Characterization of the effects of nonspecific xenon-protein interactions on
      (129)Xe chemical shifts in aqueous solution: further development of xenon as a
      biomolecular probe.
AB  - The sensitivity of (129)Xe chemical shifts to weak nonspecific xenon-protein
      interactions has suggested the use of xenon to probe biomolecular structure and
      interactions. The realization of this potential necessitates a further
      understanding of how different macromolecular properties influence the (129)Xe
      chemical shift in aqueous solution. Toward this goal, we have acquired (129)Xe
      NMR spectra of xenon dissolved in amino acid, peptide, and protein solutions
      under both native and denaturing conditions. In general, these cosolutes induce
      (129)Xe chemical shifts that are downfield relative to the shift in water, as
      they deshield the xenon nucleus through weak, diffusion-mediated interactions.
      Correlations between the extent of deshielding and molecular properties including
      chemical identity, structure, and charge are reported. Xenon deshielding was
      found to depend linearly on protein size under denaturing solution conditions;
      the denaturant itself has a characteristic effect on the (129)Xe chemical shift
      that likely results from a change in the xenon solvation shell structure. In
      native protein solutions, contributions to the overall (129)Xe chemical shift
      arise from the presence of weak xenon binding either in cavities or at the
      protein surface. Potential applications of xenon as a probe of biological systems
      including the detection of conformational changes and the possible quantification
      of buried surface area at protein-protein interfaces are discussed.

PMID- 11531367
TI  - Rheology of blood by NMR.
AB  - Pipe flow of blood in tubes of 1 and 7 mm inner diameter, respectively, was
      investigated employing two-dimensional NMR velocity imaging and PFG propagator
      measurements at different Reynolds numbers between 10 and 3500. The results are
      compared to flow of a water/glycerol mixture of matching viscosity under
      identical conditions. The transition from laminar to turbulent flow is observed
      by both a flattening of the velocity profile and a change of the propagator
      shape. For blood flow this transition is found to be shifted toward higher
      Reynolds numbers as compared to the transition of the water/glycerol mixture.
      This observation is in agreement with predictions from hydraulic measurements and
      is a consequence of the non-Newtonian flow characteristics of blood as a
      suspension of erythrocytes and plasma. Likewise, a deviation from the laminar
      flow condition is observed for blood at low Reynolds numbers between 10 and 100.
      This phenomenon is unknown for Newtonian liquids and is explained by the onset of
      a geometrical arrangement of the erythrocytes, the so-called rouleaux effect.

PMID- 11531368
TI  - Rotor synchronization of radiofrequency and gradient pulses in high-resolution
      magic angle spinning NMR.
AB  - We have investigated the extent to which rotor synchronization of radiofrequency
      pulses leads to spectral improvement in high-resolution magic angle spinning NMR
      experiments. Several pulse sequences were tested, and the effect was found to be
      maximal in homonuclear TOCSY spectra. The physicochemical nature of the sample
      plays a role in the phenomenon, as rotor synchronization allows the refocusing of
      residual anisotropic interactions. However, even in a liquid sample the effects
      were visible. Radial inhomogeneities of the radiofrequency field were identified
      as an important source of the problem.

PMID- 11531369
TI  - Cross correlation between the dipole-dipole interaction and the Curie spin
      relaxation: the effect of anisotropic magnetic susceptibility.
AB  - Cross-correlated relaxation caused by the interference of nuclear dipole-dipole
      interaction and the Curie spin relaxation (DD-CSR cross relaxation) is
      generalized to treat the case of anisotropic magnetic susceptibility, including
      the important case where the latter originates from zero-field splitting. It is
      shown that the phenomenon of DD-CSR cross relaxation is absolutely general and to
      be expected under any electronic configuration. The results of the generalization
      are presented for a model system, and the consequences for paramagnetic
      metalloproteins are illustrated with an example of cerium(III)-substituted
      calbindin. The effects of the magnetic anisotropy are found to be substantial.

PMID- 11531370
TI  - Carr-Purcell sequences with composite pulses.
AB  - We present novel Carr-Purcell-like sequences using composite pulses that exhibit
      improved performance in strongly inhomogeneous fields. The sequences are designed
      to retain the intrinsic error correction of the standard Carr-Purcell-Meiboom
      Gill (CPMG) sequence. This is achieved by matching the excitation pulse with the
      refocusing cycle such that the initial transverse magnetization lies along the
      axis n(Beta) characterizing the overall rotation of the refocusing cycle. Such
      sequences are suitable for relaxation measurements. It is shown that in
      sufficiently inhomogeneous fields, the echo amplitudes have an initial transient
      modulation that is limited to the first few echoes and then decay with the
      intrinsic relaxation time of the sample. We show different examples of such
      sequences that are constructed from simple composite pulses. Sequences of the
      form 90 degrees (0)-(90 degrees (90-theta/2)-theta(180-theta/2)-90 degrees (90
      theta/2))(n) with theta approximately 90 degrees and 270 degrees generate signal
      over a bandwidth larger than that of the conventional CPMG sequence, resulting in
      an improved signal-to-noise ratio in inhomogeneous fields. The new sequence 127
      degrees (x,y)-(127 degrees (x)-127 degrees (-x))(n) only excites signal off
      resonance with a spectrum that is bimodal, peaking at Delta omega(0)=+/-omega(1).
      Depending on the phase and exact timing of the first pulse, symmetric or
      antisymmetric excitation is obtained. We also demonstrate several new sequences
      with improved dependence on the RF field strength. The sequence (22.5 degrees
      (67.5)-90 degrees (-22.5))-(90 degrees (67.5)-45 degrees (157.5)-90 degrees
      (67.5))(n) has the property that the phase of the signal depends on B(1),
      allowing coarse B(1) imaging in a one-dimensional experiment.

PMID- 11531371
TI  - Detection of gamma-aminobutyric acid (GABA) by longitudinal scalar order
      difference editing.
AB  - Two novel spectral editing techniques for the in vivo detection of gamma
      aminobutyric acid (GABA) are presented. The techniques rely on the generation of
      longitudinal scalar order (LSO) coherences, which in combination with J
      difference editing results in the selective detection of GABA. The utilization of
      LSO coherences makes the editing sequences insensitive to phase and frequency
      instabilities. Furthermore, the spectral editing selectivity can be increased
      independent of the echo time, thereby opening the echo time for state-of-the-art
      water suppression and/or spatial localization techniques. The performance of the
      LSO editing techniques is theoretically demonstrated with product operator
      calculations and density matrix simulations and experimentally evaluated on
      phantoms in vitro and on human brain in vivo.

PMID- 11531372
TI  - A new approach to visualizing spectral density functions and deriving motional
      correlation time distributions: applications to an alpha-helix-forming peptide
      and to a well-folded protein.
AB  - A new approach to visualizing spectral densities and analyzing NMR relaxation
      data has been developed. By plotting the spectral density function, J(omega), as
      F(omega)=2 omega J(omega) on the log-log scale, the distribution of motional
      correlation times can be easily visualized. F(omega) is calculated from
      experimental data using a multi-Lorentzian expansion that is insensitive to the
      number of Lorentzians used and allows contributions from overall tumbling and
      internal motions to be separated without explicitly determining values for
      correlation times and their weighting coefficients. To demonstrate the approach,
      (15)N and (13)C NMR relaxation data have been analyzed for backbone NH and
      C(alpha)H groups in an alpha-helix-forming peptide 17mer and in a well-folded 138
      residue protein, and the functions F(omega) have been calculated and deconvoluted
      for contributions from overall tumbling and internal motions. Overall tumbling
      correlation time distribution maxima yield essentially the same overall
      correlation times obtained using the Lipari-Szabo model and other standard NMR
      relaxation data analyses. Internal motional correlational times for NH and
      C(alpha)H bond motions fall in the range from 100 ps to about 1 ns. Slower
      overall molecular tumbling leads to better separation of internal motional
      correlation time distributions from those of overall tumbling. The usefulness of
      the approach rests in its ability to visualize spectral densities and to define
      and separate frequency distributions for molecular motions.

PMID- 11531373
TI  - A pulse EPR study of longitudinal relaxation of the stable radical in gamma
      irradiated L-alanine.
AB  - The longitudinal relaxation rate of the first stable alanine radical, SAR1, was
      studied by employing pulse EPR technique over a wide temperature interval (5-290
      K). The complex nonexponential recovery of the longitudinal magnetization in this
      temperature interval has been described with two characteristic relaxation times,
      1/T*(1a) as the faster component and 1/T*(1b) as the slower component,
      respectively. It was shown that 1/T*(1a) is strongly affected by the CH(3) group
      dynamics of the SAR1 center. The complete temperature dependence of 1/T*(1a) was
      described by invoking several relaxation mechanisms that involve hindered motion
      of the CH(3) group from classical rotational motion to coherent rotational
      tunneling. It was shown that all relevant relaxation mechanisms are determined by
      a single correlation time with the potential barrier (Delta E/k=1570 K). On the
      other hand the temperature dependence of 1/T*(1b) is related to the motional
      dynamics of the neighborly NH(3) and CH(3) groups. We found a larger average
      potential barrier for this motion (Delta E/k=2150 K) corresponding to smaller
      tunneling frequencies of the neighbor groups.

PMID- 11531374
TI  - Electron spin relaxation of triarylmethyl radicals in fluid solution.
AB  - Electron spin relaxation times of a Nycomed triarylmethyl radical (sym-trityl) in
      water, 1:1 water:glycerol, and 1:9 water:glycerol were measured at L-band, S
      band, and X-band by pulsed EPR methods. In H(2)O solution, T(1) is 17+/-1 micros
      at X-band at ambient temperature, is nearly independent of microwave frequency,
      and exhibits little dependence on viscosity. The temperature dependence of T(1)
      in 1:1 water:glycerol is characteristic of domination by a Raman process between
      20 and 80 K. The increased spin-lattice relaxation rates at higher temperatures,
      including room temperature, are attributed to a local vibrational mode that
      modulates spin-orbit coupling. In H(2)O solution, T(2) is 11+/-1 micros at X
      band, increasing to 13+/-1 micros at L-band. For more viscous solvent mixtures,
      T(2) is much shorter than T(1) and weakly frequency dependent, which indicates
      that incomplete motional averaging of hyperfine anisotropy makes a significant
      contribution to T(2). In water and 1:1 water:glycerol solutions continuous wave
      EPR linewidths are not relaxation determined, but become relaxation determined in
      the higher viscosity 1:9 water:glycerol solutions. The Lorentzian component of
      the 250-MHz linewidths as a function of viscosity is in good agreement with T(2)
      determined contributions to the linewidths at higher frequencies.

PMID- 11531375
TI  - Two-dimensional NMR of velocity exchange: VEXSY and SERPENT.
AB  - Two different multidimensional pulsed field gradient sequences are compared which
      have the purpose of correlating spin displacements in different time intervals
      with each other. The simplest possible sequence, three-pulse SERPENT, measures
      displacements in two interleaved time intervals, while in VEXSY, consisting of
      two independent pairs of gradient pulses separated by a mixing time,
      displacements during the two encoding intervals are compared to each other. The
      formalism for both sequences is discussed in q space and in displacement space
      and common features as well as differences between the two types of experiments
      are highlighted, employing the particular case of the concurrent VEXSY scheme
      which allows treatment according to both formalisms.

PMID- 11531376
TI  - Low-power water suppression by hyperbolic secant pulses with controlled offsets
      and delays (WASHCODE).
AB  - A class of chemical-shift-selective (CHESS) water suppression (WS) schemes is
      presented in which the characteristic frequency-domain excitation profiles of
      "adiabatic" full-passage (AFP) RF pulses are utilized for frequency-selective
      excitation of the water resonance. In the proposed WS schemes, dubbed WASHCODE,
      hyperbolic secant (HS) pulses were used as the AFP pulses. Besides the high
      immunity of WS efficiency toward B(1) inhomogeneity, these sequences also exhibit
      extraordinary insensitivity to the dispersion of the water T(1) relaxation times.
      The actual performance of the proposed WS schemes was achieved in particular by
      optimizing the frequency offsets of WS HS pulses and the time intervals between
      them. To reduce the RF power requirements of these WS sequences for in vivo
      applications, HS pulses with the minimum possible frequency bandwidths were
      employed, which also substantially reduced the adverse effects on the observed
      proton MR spectra. The proposed WS schemes were evaluated by simulations based on
      the Bloch equations. Several WS sequences which looked particularly promising
      were verified experimentally on the human brain on a 3 T MR scanner using very
      short echo-time STEAM for volume selection and a standard single-loop surface
      coil for both signal transmission and reception. Routinely, water-suppression
      factors ranging from 2000 to 4000 were achieved in vivo without additional
      adjustment of parameters for individual subjects and without violating legal
      safety limits.

PMID- 11531378
TI  - Indirect NMR detection in solids with multiple cross-polarization periods.
AB  - The use of indirect detection for signal enhancement in solids is much less
      common than in liquids, but has attracted renewed interest recently. In this work
      we describe an indirect detection scheme that offers a large signal enhancement
      for rare spins in solids. The method uses multiple periods of cross polarization,
      each followed by an evolution period. The latter is increased stepwise in a
      pseudo 2D experiment, in which the signal of the rare spin is detected as
      modulation of the abundant spin. As an illustration of this method, the natural
      abundance deuterium NMR spectrum of a static powder sample of 1,2,4,5
      tetramethylbenzene is presented.

PMID- 11531377
TI  - S(3)E-E.COSY methods for the measurement of (19)F associated scalar and dipolar
      coupling constants.
AB  - A (1)H-(19)F spin state selective excitation (S(3)E) pulse sequence element has
      been applied in combination with (1)H homonuclear mixing to create E.COSY-type
      experiments designed to measure scalar J(HF2') and J(HH2') and residual dipolar
      D(HF2') and D(HH2') couplings in 2'-deoxy-2'-fluoro-sugars. The (1)H-(19)F S(3)E
      pulse sequence element, which resembles a simple INEPT sequence, achieves spin
      state-selective correlation between geminal (1)H-(19)F spin pairs by linear
      combination of in-phase (19)F magnetization and anti-phase magnetization evolved
      from (1)H. Since the S(3)E sequence converts both (19)F and (1)H steady-state
      polarization into observable coherences, an approximately twofold signal increase
      is observed for fully relaxed (1)H-(19)F spin pairs with respect to a standard
      (1)H coupled (19)F 1D experiment. The improved sensitivity and resolution
      afforded by the use of (1)H-(19)F S(3)E E.COSY-type experiments for measuring
      couplings is demonstrated on the nucleoside 9-(2',3'-dideoxy-2'-fluoro-beta-D
      threo-pentofuranosyl)adenine (beta-FddA) and on a selectively 2'-fluorine labeled
      21mer RNA oligonucleotide.

PMID- 11531379
TI  - MR imaging with phase encoding of intermolecular multiple quantum coherences.
AB  - Novel 2D and 3D pulse sequences producing images through the phase encoding of
      intermolecular multiple quantum coherences (i-MQCs) are presented. The signal
      acquired with these sequences is free from intermolecular zero quantum coherences
      (i-ZQCs) which are not phase encoded and additional phase cycling eliminates
      artifacts. Phase encoding during the n-quantum evolution period provides n times
      the resolution expected from equivalent phase encoding of the reconverted single
      quantum coherences. These sequences have potential applications for producing i
      MQC images of biological tissues as well as nonbiological materials with
      substantial amounts of water.

PMID- 11531380
TI  - Automatic discovery of sub-molecular sequence domains in multi-aligned sequences:
      a dynamic programming algorithm for multiple alignment segmentation.
AB  - Automatic identification of sub-structures in multi-aligned sequences is of great
      importance for effective and objective structural/functional domain annotation,
      phylogenetic treeing and other molecular analyses. We present a segmentation
      algorithm that optimally partitions a given multi-alignment into a set of
      potentially biologically significant blocks, or segments. This algorithm applies
      dynamic programming and progressive optimization to the statistical profile of a
      multi-alignment in order to optimally demarcate relatively homogenous sub
      regions. Using this algorithm, a large multi-alignment of eukaryotic 16S rRNA was
      analyzed. Three types of sequence patterns were identified automatically and
      efficiently: shared conserved domain; shared variable motif; and rare signature
      sequence. Results were consistent with the patterns identified through
      independent phylogenetic and structural approaches. This algorithm facilitates
      the automation of sequence-based molecular structural and evolutionary analyses
      through statistical modeling and high performance computation.

PMID- 11531381
TI  - Host-limited dynamics of autoparasitoids.
AB  - Autoparasitoids, an important class of intraguild predators used in classical
      biological control, have a unique biology. Females develop as primary
      endoparasitoids of scale insects and whiteflies. Males develop at the expense of
      conspecific or heterospecific parasitoid prepupae. To evaluate the effect of
      autoparasitism on host suppression, system stability, and parasitoid coexistence,
      stage-structured differential equation models are developed and analysed. For a
      host-parasitoid system, autoparasitism stabilizes host-parasitoid oscillations
      generated by developmental delays of the parasitoid. In host-autoparasitoid
      primary parasitoid systems, a distinction between obligate (i.e. parasitoid only
      attacks conspecifics for the production of males) and facultative (i.e.
      parasitoid attacks conspecifics and heterospecifics for the production of males)
      autoparasitism is drawn. Coexistence between an obligate autoparasitoid and
      primary parasitoid occurs if and only if the autoparasitoid can invade at lower
      host densities than the primary parasitoid, and the primary parasitoid can
      suppress the host to a lower equilibrium density than the autoparasitoid. When
      coexistence occurs, the primary parasitoid determines the host equilibrium
      abundance. Interactions between facultative autoparasitoids and primary
      parasitoids can lead to a priority effect, and, less likely, to coexistence. When
      coexistence occurs, the invasion of the facultative autoparasitoid into the host
      primary parasitoid system raises the equilibrium density of the host. In either
      coexistence scenario, the invasion of an autoparasitoid can stabilize an unstable
      host-primary parasitoid system. The analysis concludes by showing that the
      introduction of an autoparasitoid to a host-primary parasitoid system can improve
      host suppression in the short-term despite possible long-term disruption.

PMID- 11531382
TI  - Topology of gap junction networks in C. elegans.
AB  - Gap junctions are prevalent in every nervous system, but their role in
      information processing remains largely unknown. In C. elegans, the role of gap
      junctional communication in touch sensitivity has been demonstrated. In this
      animal, the entire complement of gap junctions in the nervous system is
      documented, therefore providing a good model for the computational investigation
      of circuit functions of gap junctions.We explored several hypotheses about the
      role of gap junctions in the nervous system of C. elegans by systematically
      analysing an anatomical database with recursive algorithms. We find that gap
      junctions connect different sets of neurons from those connected by chemical
      synapses. In addition, when analysing the topology of the gap-junction networks,
      we find that, surprisingly, most (92%) neurons in the worm are linked in a single
      gap-junction network. The worm nervous system can only be divided into smaller
      networks by assuming that two or more gap junctions are necessary for functional
      coupling or that neural activity has limited propagation. However, these groups,
      and others identified using algorithms with subsets or combinations of
      restrictive criteria, do not correspond to any known circuits identified in
      genetic and behavioral studies. Finally, we notice that the function of some gap
      junctions appears linked to their precise location on the neuronal processes. We
      propose that the location of the gap junctions within the neuron determines their
      functional role.

PMID- 11531383
TI  - Polymorphism maintenance in populations with mixed random mating and apomixis
      subjected to stabilizing and cyclical selection.
AB  - We analysed a diploid population model with a mixed breeding system that includes
      panmixia and apomixis. Each individual produces a part (ss) of its progeny by
      random mating, the remainder (1-ss) being a result of precise copying (vegetative
      reproduction or apomixis) of the parental genotype. Both constant and
      periodically varying selection regimes were considered. In the main model, the
      selected trait was controlled by two diallelic additive or semidominant loci, A/a
      and B/b, whereas the parameter of breeding system (ss) was genotype-independent.
      A numerical iteration of the evolutionary equations were used to evaluate the
      proportion (V) of population trajectories converging to internal (polymorphic)
      fixed points. The results were the following. (a) A complex pattern of dependence
      of polymorphism stability on interaction among the breeding system, recombination
      rate, and the genetic architecture of the selected trait emerged. (b) The
      recombination provided some advantage to sex at intermediate period lengths and
      strong-to-moderate selection intensities. (c) The complex limiting behavior (CLB)
      was quite compatible with sexual reproduction, at least within the framework of
      pure genetic (not including variations in population density) models of
      multilocus varying selection.

PMID- 11531384
TI  - Fractal dimensions and multifractility in vascular branching.
AB  - A definition for the fractal dimension of a vascular tree is proposed based on
      the hemodynamic function of the tree and in terms of two key branching
      parameters: the asymmetry ratio of arterial bifurcations and the power law
      exponent governing the relation between vessel diameter and flow. Data from the
      cardiovascular system, which generally exhibit considerable scatter in the values
      of these two parameters, are found to produce the same degree of scatter in the
      value of the fractal dimension. When this scatter is explored for a multifractal
      pattern, however, it is found that the required collapse onto a single curve is
      achieved in terms of the coarse Holder exponent. Thus, the presence of
      multifractility is confirmed, and the legitimacy of the defined dimension is
      affirmed in the sense of the theoretical Hausdorff limit in as much as this limit
      can be reached with experimental data.

PMID- 11531385
TI  - A mathematical framework to study the effects of growth factor influences on
      fracture healing.
AB  - During fracture healing, multipotential stem cells differentiate into specialized
      cells responsible for producing the different tissues involved in the bone
      regeneration process. This cell differentiation has been shown to be regulated by
      locally expressed growth factors. The details of their regulatory mechanisms need
      to be understood. In this work, we present a two-dimensional mathematical model
      of the bone healing process for moderate fracture gap sizes and fracture
      stability. The inflammatory and tissue regeneration stages of healing are
      simulated by modeling mesenchymal cell migration; mesenchymal cell, chondrocyte
      and osteoblast proliferation and differentiation, and extracellular matrix
      synthesis and degradation over time. The effects of two generic growth factors on
      cell differentiation are based on the experimentally studied chondrogenic and
      osteogenic effects of bone morphogenetic proteins-2 and 4 and transforming growth
      factor-beta-1, respectively. The model successfully simulates the progression of
      healing and predicts that the rate of osteogenic growth factor production by
      osteoblasts and the duration of the initial release of growth factors upon injury
      are particularly important parameters for complete ossification and successful
      healing. This temporo-spatial model of fracture healing is the first model to
      consider the effects of growth factors. It will help us understand the regulatory
      mechanisms involved in bone regeneration and provides a mathematical framework
      with which to design experiments and understand pathological conditions.

PMID- 11531386
TI  - Trabecular eccentricity and bone adaptation.
AB  - It is well established that bones functionally adapt by mechanisms that control
      tissue density, whole bone geometry, and trabecular orientation. In this study,
      we propose the existence of another such powerful mechanism, namely, trabecular
      eccentricity, i.e. non-central placement of trabecular bone within a cortical
      envelope. In the human femoral neck, trabecular eccentricity results in a thicker
      cortical shell on the inferior than superior aspect. In an overall context of
      expanding understanding of bone adaptation, the goal of this study was to
      demonstrate the biomechanical significance of, and provide a mechanistic
      explanation for, the relationship between trabecular eccentricity and stresses in
      the human femoral neck. Using composite beam theory, we showed that the
      biomechanical effects of eccentricity during a habitual loading situation were to
      increase the stress at the superior aspect of the neck and decrease the stress at
      the inferior aspect, resulting in an overall protective effect. Further,
      increasing eccentricity had a stress-reducing effect equivalent to that of
      increasing cortical thickness or increasing trabecular modulus. We conclude that
      an asymmetric placement of trabecular bone within a cortical bone envelope
      represents yet another mechanism by which whole bones can adapt to mechanical
      demands.

PMID- 11531387
TI  - Global stability, local stability and permanence in model food webs.
AB  - The dynamical theory of food webs has been based typically on local stability
      analysis. The relevance of local stability to food web properties has been
      questioned because local stability holds only in the immediate vicinity of the
      equilibrium and provides no information about the size of the basin of
      attraction. Local stability does not guarantee persistence of food webs in
      stochastic environments. Moreover, local stability excludes more complex dynamics
      such as periodic and chaotic behaviors, which may allow persistence. Global
      stability and permanence could be better criteria of community persistence. Our
      simulation analysis suggests that these three stability measures are
      qualitatively consistent in that all three predict decreasing stability with
      increasing complexity. Some new predictions on how stability depends on food web
      configurations are generated here: a consumer-victim link has a smaller effect on
      the probabilities of stability, as measured by all three stability criteria, than
      a pair of recipient-controlled and donor-controlled links; a recipient-controlled
      link has a larger effect on the probabilities of local stability and permanence
      than a donor-controlled link, while they have the same effect on the probability
      of global stability; food webs with equal proportions of donor-controlled and
      recipient-controlled links are less stable than those with different proportions.

PMID- 11531388
TI  - The dynamics of the macromolecular composition of biomass.
AB  - The biomass composition of microorganisms depends on the growth conditions. This
      study explores whether a two-component model can explain how the elemental and
      macromolecular composition of the biomass of bacteria varies with the specific
      growth rate. The model describes the rates at which microorganisms assimilate
      substrates into reserves and utilize reserves for maintenance and growth. Crucial
      model assumptions are that biomass consists of reserves and structure and that
      each of these components has an invariant composition. The composition of biomass
      can vary when the ratio between reserves and structure varies. Literature data on
      the macromolecular composition of Escherichia coli, cultivated on various
      substrates, show that the protein, RNA and DNA content of biomass follow a
      distinctive trend when plotted as a function of the dry-weight-specific growth
      rate. This observation leads to the proposition that the macromolecular
      composition of E. coli depends directly on the growth rate, and only indirectly
      on the carbon- and energy-source used as substrate. We show that the variation of
      the macromolecular composition of E. coli over its entire range of growth rates
      can be described with invariant macromolecular compositions of the reserve and
      structural components of biomass. The model is also applied to our data on a
      succinate-limited continuous culture of Paracoccus denitrificans.

PMID- 11531389
TI  - Spreading disease through social groupings in competition.
AB  - Many animal populations live in social groups which avoid contact with other
      conspecific groups for at least part of the year. This may give rise to
      competition between groups for items such as shelter, land and mates. We couple
      intra-specific group competition with disease dynamics to investigate how
      infectious diseases may spread through population subgroups, particularly with
      reference to the contact rates between groups. Our model uses a nonlinear systems
      of ODEs for which steady-state analysis is carried out in the simplest two-group
      system. This indicates that coexistence of social groups is possible with the
      disease or that competitive exclusion occurs with one group dying out whilst the
      other retains disease. Moreover, we show that in certain circumstances the model
      can exhibit multistability and we discuss the ecological implications of this
      result in relation to contact between social groups.

PMID- 11531390
TI  - Animal research and publication ethics.

PMID- 11531391
TI  - Veterinary education and problem-based learning.

PMID- 11531392
TI  - Oral fluid therapy for treatment of neonatal diarrhoea in calves.

PMID- 11531393
TI  - Should the vet, and not just the wellies, be green?

PMID- 11531394
TI  - Canine idiopathic dilated cardiomyopathy. Part I: Aetiology, clinical
      characteristics, epidemiology and pathology.
AB  - Dilated cardiomyopathy (DCM), characterized by chamber dilatation and myocardial
      systolic and diastolic dysfunction, is one of the most common heart diseases in
      dogs. The aetiology of the myocardial hypokineis is seldom known in the
      individual case of DCM, although several theories concerning genetic,
      nutritional, metabolic, inflammatory, infectious, or drug- or toxin-induced
      myocardial disease have been discussed. DCM is often referred to as being breed
      specific for Boxers, Doberman Pinschers, English Cocker Spaniels and other
      breeds. Review of reports on histopathologic findings in canine DCM reveals two
      histologically distinct forms of DCM; (1) cardiomyopathy of boxers and of
      Doberman pinschers, corresponding to the "fatty infiltration-degenerative" type,
      and (2) the form seen in many giant, large- and medium-sized breeds, including
      some boxers and Doberman pinschers, which can be classified as the "attenuated
      wavy fiber" type of DCM. The classification of canine idiopathic DCM according to
      histologic findigns seems superior to classification suggesting breed-specific
      syndromes, as some breeds (i.e. boxers and Doberman pinschers) may be affected by
      both diseases. However, ante mortem aetiological diagnosis of DCM is difficult.
      DCM carries a poor prognosis in dogs, and few prognostic indicators have been
      identified.

PMID- 11531395
TI  - Atypical forms of canine leishmaniosis.
AB  - Canine leishmaniosis is a common disease in the Mediterranean area, but sporadic
      cases in dogs having travelled through endemic regions are also reported. The
      disease's evolution is usually chronic and symptoms are either non-specific
      (fever, weight loss, lethargy, enlarged lymph nodes), dermatological, renal or
      ocular. The purpose of this article is to review the literature and to describe
      our own experience of certain atypical forms of canine leishmaniosis. These
      include specific skin lesions, monoclonal gammopathy, renal failure (without any
      other signs), chronic colitis, haemostatic problems and disorders of the
      cardiovascular, respiratory and musculo-skeletal systems.

PMID- 11531396
TI  - The distribution of cartilage oligomeric matrix protein (COMP) in equine carpal
      articular cartilage and its variation with exercise and cartilage deterioration.
AB  - Based on previous studies where tendons receiving the most load have been shown
      to have the highest levels of cartilage oligomeric matrix protein (COMP), we
      hypothesized that COMP distribution in articular cartilage may be influenced by
      mechanical loading. This investigation aimed (a) to describe the pattern of COMP
      immunoreactivity in middle carpal joint cartilage of two-year-old Thoroughbred
      horses; (b) to determine topographical variations; (c) to compare high (group 1)
      and low (group 2) intensity training and (d) to describe COMP immunoreactivity at
      sites with early osteoarthritis. Group 1 (n =6) underwent a 19 week high
      intensity treadmill training programme and group 2 (n =6) were given daily
      walking until euthanasia. Dorsal and palmar sites on radial and third carpal
      articular surfaces were prepared. Immunohistochemistry was performed with
      polyclonal rabbit anti-equine COMP antiserum using a biotin
      streptavidin/peroxidase method. Results showed: (a) intracellular
      immunoreactivity was present in all cartilage zones, but the distribution of COMP
      staining within the matrix varied between cartilage zones; (b) differences in
      distribution between sites were not observed, but total COMP levels in exercised
      horses (n =2) did vary between sites with dorsal sites containing less COMP than
      palmar sites on the radial, intermediate and third carpal lateral facet; (c)
      group 1 cartilage showed marked interterritorial distribution in the deep layer
      compared to group 2 where staining was more generalized throughout the matrix and
      (d) fibrillated cartilage showed increased local immunoreactivity in the matrix.
      These findings demonstrate zonal variations in equine COMP distribution which may
      be influenced by loading.

PMID- 11531397
TI  - Comparison of two oral electrolyte solutions for the treatment of dehydrated
      calves with experimentally-induced diarrhoea.
AB  - We compared the ability of two oral electrolyte solutions to resuscitate calves
      with experimentally induced diarrhoea and dehydration. Sucrose solution,
      furosemide, spironolactone, and hydrochlorothiazide were administered to 18 male
      Holstein-Friesian calves to induce diarrhoea and dehydration. Clinical changes
      after 24 h included severe diarrhoea, moderate dehydration (8-10% body weight),
      azotemia, and clinical depression. Calves were then randomly assigned to one of
      three treatment groups (milk replacer, 2 L every 12 h; hyperosmotic oral
      electrolyte solution, 2 L every 12 h; iso-osmotic oral electrolyte solution, 1.5
      L every 6 to 12 h) and followed for an additional 48 h. Compared to feeding milk
      replacer, the hyperosmotic solution significantly (P< 0.05) improved hydration
      status, increased body weight, maintained urine production, decreased the degree
      of clinical depression and prevented development of metabolic acidosis, although
      serum glucose concentration was decreased at 24 h and 48 h. The hyperosmotic
      solution produced a similar resuscitative response to the iso-osmotic solution,
      but maintained higher serum glucose concentrations and lower serum beta-OH
      butyrate and non-esterified fatty-acid concentrations, indicating that the
      hyperosmotic solution provided greater nutritional support. The hyperosmotic
      solution rehydrated calves faster and more effectively than feeding equivalent
      volumes of milk replacer and can, therefore, be recommended as part of the
      initial treatment of dehydrated calves with diarrhoea.

PMID- 11531398
TI  - Control of infectious diseases of wildlife in Europe.
AB  - During the last 30 years, new epidemiological patterns have emerged as free
      ranging wildlife have become progressively more involved in the epidemiology of
      both common and emerging infectious diseases of humans and domestic animals. This
      has been seen in rabies, bovine tuberculosis and more recently in wild-boar
      classical swine fever. Emerging diseases are of interest to veterinarians as well
      as public health officials but attempts to control these diseases have not always
      been successful as in wildlife populations control of either host or pathogen can
      present particular problems. Lessons should be learnt from previous experiences
      to help in the management of new emerging diseases in the future.

PMID- 11531399
TI  - The influence of lameness on equine stride length consistency.
AB  - The aim of this study was to assess the influence of orthopaedic pain on the
      variation of stride length as a kinematic system-parameter in 21 horses with
      forelimb lameness. Data were collected while the horses were trotting on a
      treadmill during a minimum of 12 motion cycles, both before and after intra
      articular or perineural anaesthesia. Stride length was assessed for each motion
      cycle, and the mean and standard deviation were calculated for each condition.
      Forelimb lameness was documented as percentage of asymmetry of vertical head
      movement. With significant decrease of forelimb lameness after regional
      anaesthesia, the SD of stride length increased significantly (+0.35%, P< 0.05).
      Our results show that in the presence of orthopaedic pain horses keep stride
      variability low, possibly because the lame horse employs an optimum compensatory
      mechanism to reduce the pain in the affected limb, and every deviation from this
      pattern increases pain.

PMID- 11531400
TI  - Plasma inorganic iodine and thyroxine concentrations for beef cows in late
      pregnancy and early lactation associated with different levels of dietary iodine
      supplementation.

PMID- 11531401
TI  - Conception rate following progesterone supplementation after second insemination
      in dairy cows.

PMID- 11531402
TI  - Reverse genetics of influenza virus.
AB  - Reverse genetics of negative-sense RNA viruses, which enables one to generate
      virus entirely from cloned cDNA, has progressed rapidly over the past decade.
      However, despite the relative ease with which nonsegmented negative-sense RNA
      viruses can now be produced from plasmids, the ability to generate viruses with
      segmented genomes has lagged considerably, largely because of the inherent
      technical difficulties in providing all viral RNAs and proteins from cloned cDNA.
      A breakthrough in reverse genetics technology in the influenza virus field came
      in 1999, when we (Neumann et al., 1999, Proc. Natl. Acad. Sci. USA 96, 9345-9350)
      and others (Fodor et al., 1999, J. Virol. 73, 9679-9682) exploited a new approach
      to viral RNA production. In this review, we discuss the background for this
      advance, the systems that are now available for the generation of influenza
      viruses, and the implications of these developments for the future of virus
      research.

PMID- 11531403
TI  - De novo initiation of viral RNA-dependent RNA synthesis.
AB  - RNA viruses use several initiation strategies to ensure that their RNAs are
      synthesized in appropriate amounts, have correct termini, and can be translated
      efficiently. Many viruses with genomes of single-stranded positive-, negative-,
      and double-stranded RNA initiate RNA synthesis by a de novo (primer-independent)
      mechanism. This review summarizes biochemical features and variations of de novo
      initiation in viral RNA replication.

PMID- 11531404
TI  - HIV-1 LTR subtype and perinatal transmission.
AB  - Multiple subtypes of HIV-1 have been identified; however, there is little data on
      the relative transmissibility of viruses belonging to different subtypes. A
      matched case-control study addressed whether viruses with different long terminal
      repeat (LTR) subtypes were transmitted equally from mother to infant. The LTR
      subtype was determined for 45 matched cases and controls who participated in a
      clinical trial in Tanzania. HIV-1 subtypes A, C, and D and intersubtype
      recombinant sequences were identified. Exact matched logistic regression analysis
      showed that viruses containing subtype A or intersubtype recombinant LTRs were
      3.2 and 4.8 times more likely to be transmitted from mother to infant than
      viruses with subtype D LTRs. Viruses containing subtype C LTRs were 6.1 times
      more likely to be transmitted than those with subtype D LTRs. These differences
      in transmission were independent of maternal CD4 at enrollment. Thus, it appears
      that HIV-1 subtype may be associated with differing rates of perinatal
      transmission in Tanzania.

PMID- 11531405
TI  - Hepatitis B virus X protein interferes with cell viability through interaction
      with the p127-kDa UV-damaged DNA-binding protein.
AB  - The hepatitis B virus X protein (HBx) is essential for establishing natural viral
      infection and has been implicated in the development of liver cancer associated
      with chronic infection. The basis for HBx function in either process is not
      understood. In cell culture, HBx exhibits pleiotropic activities affecting
      transcription, DNA repair, cell growth, and apoptotic cell death. Numerous
      cellular proteins including the p127-kDa subunit of UV-damaged DNA-binding
      activity have been reported to interact with HBx but the functional significance
      of these interactions remains unclear. Here we show that the binding of HBx to
      p127 interferes with cell viability. Mutational analysis reveals that HBx
      contacts p127 via a region to which no function has been assigned previously. An
      HBx variant bearing a single-charge reversal substitution within this region
      loses p127 binding and concomitant cytotoxicity. This mutant regains activity
      when directly fused to p127. These studies confirm that p127 is an important
      cellular target of HBx, and they indicate that HBx does not exert its effect by
      sequestering p127, and thereby preventing its normal function, but instead by
      conferring to p127 a deleterious activity.

PMID- 11531406
TI  - Molecular and phylogenetic analyses of 16 novel simian T cell leukemia virus type
      1 from Africa: close relationship of STLV-1 from Allenopithecus nigroviridis to
      HTLV-1 subtype B strains.
AB  - A serological survey searching for antibodies reacting with human T-cell leukemia
      virus type 1 (HTLV-1) antigens was performed on a series of 263 sera/plasma
      obtained from 34 monkey species or subspecies, originating from different parts
      of Africa. Among them, 34 samples exhibited a typical HTLV-1 Western blot
      pattern. Polymerase chain reaction was performed with three primer sets specific
      either to HTLV-1/STLV-1 or HTLV-2 and encompassing gag, pol, and tax sequences,
      on genomic DNA from peripheral blood mononuclear cells of 31 animals. The
      presence of HTLV-1/simian T-cell leukemia virus type 1 (STLV-1) related viruses
      was determined in the 21 HTLV-1 seropositive animals tested but not in the 10
      HTLV-1 seronegative individuals. Proviral DNA sequences from the complete LTR
      (750 bp) and a portion of the env gene (522 bp) were determined for 16 new STLV-1
      strains; some of them originating from species for which no STLV-1 molecular data
      were available as Allenopithecus nigroviridis and Cercopithecus nictitans.
      Comparative and phylogenetic analyses revealed that these 16 new sequences belong
      to five different molecular groups. The A. nigroviridis STLV-1 strains exhibited
      a very strong nucleotide similarity with HTLV-1 of the subtype B. Furthermore,
      four novel STLV-1, found in Cercocebus torquatus, C. m. mona, C. nictitans, and
      Chlorocebus aethipos, were identical to each other and to a previously described
      Papio anubis STLV-1 strain (PAN 503) originating from the same primate center in
      Cameroon. Our data extend the range of the African primates who could be
      permissive and/or harbor naturally STLV-1 and provide new evidences of cross
      transmission of African STLV-1 between different monkey species living in the
      same environment and also of STLV-1 transmissions from some monkeys to humans in
      Central Africa.

PMID- 11531407
TI  - Enhanced accumulation of coronavirus defective interfering RNA from expressed
      negative-strand transcripts by coexpressed positive-strand RNA transcripts.
AB  - Expression of negative-strand murine coronavirus mouse hepatitis virus (MHV)
      defective interfering (DI) RNA transcripts in MHV-infected cells results in the
      accumulation of positive-strand DI RNAs (M. Joo et al., 1996, J. Virol. 70, 5769
      5776). However, the expressed negative-strand DI RNA transcripts are poor
      templates for positive-strand DI RNA synthesis. The present study demonstrated
      that DI RNA accumulation from the expressed negative-strand DI RNA transcripts in
      MHV-infected cells was enhanced by the coexpression of complementary RNA
      transcripts that correspond to the 5' region of positive-strand DI RNA. The
      positive-strand RNA transcripts corresponding to the 5' end-most 0.7-2.0 kb DI
      RNA had a similar enhancement effect. The coexpressed positive-strand RNA
      transcripts lacking the leader sequence or those containing only the leader
      sequence failed to demonstrate this enhancement effect, demonstrating that the
      presence of the leader sequence in the coexpressed positive-strand RNA
      transcripts was necessary, but not sufficient, for the enhancement of DI RNA
      accumulation from the coexpressed negative-strand DI RNA transcripts. Negative
      strand DI RNA transcripts that were coexpressed with the partial-length positive
      strand RNA transcripts were no more stable than those expressed alone, suggesting
      that a higher stability of the expressed negative-strand RNA transcripts was an
      unlikely reason for the higher DI RNA accumulation in cells coexpressing two
      complementary DI RNA transcripts. Sequence analyses unexpectedly demonstrated
      that the leader sequence of the majority of accumulated DI RNAs switched to
      helper virus derived leader sequence, suggesting that enhancement of DI RNA
      accumulation was mediated by the efficient utilization of helper virus derived
      leader sequence for DI RNA synthesis. Furthermore, our data suggested that this
      leader switching, a type of homologous RNA-RNA recombination, occurred during
      positive-strand DI RNA synthesis and that MHV positive-strand RNA synthesis
      mechanism may have a preference toward recognizing double-stranded RNA structures
      over single-stranded negative-strand RNA to produce positive-strand DI RNAs.

PMID- 11531408
TI  - Transcription from the gene encoding the herpesvirus entry receptor nectin-1
      (HveC) in nervous tissue of adult mouse.
AB  - Both human and murine forms of nectin-1 (HveC, Prr1) can serve as entry receptors
      for several neurotropic herpesviruses, including herpes simplex viruses 1 and 2
      (HSV-1, HSV-2), porcine pseudorabies virus (PRV), and bovine herpesvirus 1. HSV
      1, HSV-2, and PRV can cause lethal neurological disease in mice whether
      inoculation is directly into the central nervous system or by peripheral routes.
      Expression of nectin-1 transcripts in cells of the adult mouse nervous system was
      assessed by in situ hybridization. Specific hybridization signals were detected
      in neurons in sensory, sympathetic, and parasympathetic ganglia of the peripheral
      nervous system. In addition, specific signals were observed in neurons of the
      ventral and dorsal horns of the spinal cord and of the brain stem, cerebellum,
      cerebral cortex, hippocampus, dentate gyrus, and olfactory bulb. These results
      show that the nectin-1 gene is widely transcribed in neurons in adult mouse.
      Nectin-1 is the only known receptor capable of mediating the entry of all three
      viruses, HSV-1, HSV-2, and PRV. Its pattern of expression in the nervous system
      suggests a key role in neurological disease caused by these viruses.

PMID- 11531409
TI  - The bet gene of feline foamy virus is required for virus replication.
AB  - Foamy viruses (FV) are complex retroviruses with additional bel genes located
      between env and the 3' long-terminal repeat. The functions of the bel 2 and bet
      genes are unknown and both are dispensable for replication of the prototypic
      human foamy virus in cell cultures. We examined the function(s) of bel 2 and bet
      of the distantly related feline foamy virus (FFV) in the proviral context.
      Mutagenesis was used to alter the Bel 2 and Bet or to abrogate their expression.
      The Bel 2/Bet mutants showed a 1000-fold reduced viral titer in feline kidney
      cells; in human 293T cells, viral titer was only about 10-fold reduced compared
      to wild-type FFV. In both cell types, the Bel 2/Bet mutations resulted in a
      reduced release of FFV particles. The results indicate that FFV Bet is required
      for efficient virus replication. The functions of the Bel 2 and Bet proteins are
      discussed.

PMID- 11531410
TI  - Multiple sclerosis retrovirus particles and recombinant envelope trigger an
      abnormal immune response in vitro, by inducing polyclonal Vbeta16 T-lymphocyte
      activation.
AB  - A retroviral element (MSRV) defining a family of genetically inherited endogenous
      retroviruses (HERV-W) has recently been characterized in cell cultures from
      patients with multiple sclerosis (MS). To address the possible relationship with
      MS, direct detection of circulating virion RNA was proposed but revealed
      technically difficult to perform in standardized conditions, in the face of
      multiple endogenous HERV-W copies. A parallel approach has evaluated MSRV
      potential pathogenicity in relation to characteristic features of multiple
      sclerosis, in particular, T-lymphocyte-mediated immunopathology. We report here
      that MSRV particles induce T-lymphocyte response with a bias in the Vbeta16 chain
      usage in surface receptor, whatever the HLA DR of the donor. A recombinant MSRV
      envelope-but not core-protein reproduced similar nonconventional activation.
      Molecular analysis of Vbeta CDR3 showed that Vbeta16 expansions are polyclonal.
      Our results thus provide evidence that MSRV envelope protein can trigger an
      abnormal immune response with similar characteristics to that of superantigens.

PMID- 11531411
TI  - Mammalian reovirus L2 gene and lambda2 core spike protein sequences and whole
      genome comparisons of reoviruses type 1 Lang, type 2 Jones, and type 3 Dearing.
AB  - The reovirus L2 genome segment encodes the core spike protein lambda2, which
      mediates enzymatic reactions in 5' capping of the viral plus-strand transcripts.
      Complete nucleotide-sequence determinations were made for the L2 genome segments
      of eight mammalian reoviruses, including the prototype isolates of serotypes 1
      and 2: Lang (T1L) and Jones (T2J), respectively. Each L2 segment was found to be
      3912 or 3915 bases in length. Partial nucleotide-sequence determinations were
      also made for the 3916-base L2 segment of reovirus type 3 Dearing (T3D), the
      prototype isolate of serotype 3. The whole-genome sequence of reovirus T3D was
      reported previously. The T1L L2 analysis represents completion of the whole
      genome sequence of that isolate as well. The T2J L2 analysis leaves only the
      sequence of the M1 segment yet to be reported from the genome of that isolate.
      The T2J M1 sequence made available from analysis in another lab was used for
      initiating whole-genome comparisons of reoviruses T1L, T2J, and T3D in this
      report. The nine L2 gene sequences and deduced lambda2 protein sequences were
      used to gain further insights into the biological variability, structure, and
      functions of lambda2 through comparisons of the sequences and reference to the
      crystal structure of core-bound lambda2. Phylogenetic comparisons suggest the
      presence of three evolutionary lines of divergent L2 alleles among the nine
      isolates. Localized regions of conserved amino acids in the lambda2 crystal
      structure include active-site clefts of the RNA capping enzyme domains, sites of
      interactions between lambda2 domains within the pentameric spike structure, and
      sites of interaction between lambda2 subunits and other proteins in viral
      particles.

PMID- 11531412
TI  - The variability of hop latent viroid as induced upon heat treatment.
AB  - We have previously shown that heat treatment of hop plants infected by hop latent
      viroid (HLVd) reduces viroid levels. Here we investigate whether such heat
      treatment leads to the accumulation of sequence variability in HLVd. We observed
      a negligible level of mutated variants in HLVd under standard cultivation
      conditions. In contrast, the heat treatment of hop led to HLVd degradation and,
      simultaneously, to a significant increase in sequence variations, as judged from
      temperature gradient-gel electrophoresis analysis and cDNA library screening by
      DNA heteroduplex analysis. Thirty-one cDNA clones (9.8%) were identified as
      deviating forms. Sequencing showed mostly the presence of quadruple and triple
      mutants, suggesting an accumulation of mutations in HLVd during successive
      replication cycles. Sixty-nine percent of base changes were localised in the left
      half and 31% in the right half of the secondary structure proposed for this
      viroid. No mutations were found in the central part of the upper conserved
      region. A "hot spot" region was identified in a domain known as a "pathogenicity
      domain" in the group representative, potato spindle tuber viroid. Most mutations
      are predicted to destabilise HLVd secondary structure. All mutated cDNAs,
      however, were infectious and evolved into complex progeny populations containing
      molecular variants maintained at low levels.

PMID- 11531413
TI  - HIV-1 Vpr induces cell cycle G2 arrest in fission yeast (Schizosaccharomyces
      pombe) through a pathway involving regulatory and catalytic subunits of PP2A and
      acting on both Wee1 and Cdc25.
AB  - Viral protein R (Vpr) of human immunodeficiency virus type 1 induces G2 arrest in
      cells from distantly related eukaryotes including human and fission yeast through
      inhibitory phosphorylation of tyrosine 15 (Tyr15) on Cdc2. Since the DNA damage
      and DNA replication checkpoints also induce G2 arrest through phosphorylation of
      Tyr15, it seemed possible that Vpr induces G2 arrest through the checkpoint
      pathways. However, Vpr does not use either the early or the late checkpoint genes
      that are required for G2 arrest in response to DNA damage or inhibition of DNA
      synthesis indicating that Vpr induces G2 arrest by an alternative pathway. It was
      found that protein phosphatase 2A (PP2A) plays an important role in the induction
      of G2 arrest by Vpr since mutations in genes coding for a regulatory or catalytic
      subunit of PP2A reduce Vpr-induced G2 arrest. Vpr was also found to upregulate
      PP2A, supporting a model in which Vpr activates the PP2A holoenzyme to induce G2
      arrest. PP2A is known to interact genetically in fission yeast with the Wee1
      kinase and Cdc25 phosphatase that act on Tyr15 of Cdc2. Both Wee1 and Cdc25 play
      a role in Vpr-induced G2 arrest since a wee1 deletion reduces Vpr-induced G2
      arrest and a direct in vivo assay shows that Vpr inhibits Cdc25. Additional
      support for both Wee1 and Cdc25 playing a role in Vpr-induced G2 arrest comes
      from a genetic screen, which identified genes whose overexpression affects Vpr
      induced G2 arrest. For this genetic screen, a strain was constructed in which
      cell killing by Vpr was nearly eliminated while the effect of Vpr on the cell
      cycle was clearly indicated by an increase in cell length. Overexpression of the
      wos2 gene, an inhibitor of Wee1, suppresses Vpr-induced G2 arrest while
      overexpression of rad25, an inhibitor of Cdc25, enhances Vpr-induced G2 arrest.
      These two genes may be part of the uncharacterized pathway for Vpr-induced G2
      arrest in which Vpr upregulates PP2A to activate Wee1 and inhibit Cdc25.

PMID- 11531414
TI  - Pathogenesis of SIV pneumonia: selective replication of viral genotypes in the
      lung.
AB  - Lymphocytic interstitial pneumonia of HIV-infected individuals and SIV pneumonia
      of macaques are both characterized by diffuse infiltration of the lungs with
      lymphocytes, plasma cells, and macrophages. This study was undertaken to
      determine whether there are specific, macrophage-tropic genotypes that
      selectively replicate in the lung of macaques with SIV pneumonia, as in SIV
      encephalitis. Using a rapid, reproducible SIV/macaque model of AIDS, 11 pig
      tailed macaques were intravenously inoculated with an immunosuppressive viral
      strain, SIV/DeltaB670, and a macrophage-tropic molecule clone, SIV/17E-Fr, and
      euthanized at 3 months postinoculation. All 11 macaques had severe (6 macaques)
      or moderate (5 macaques) pneumonia. To identify the viral genotypes that were
      replicating in the lung parenchyma, bronchoalveolar lavage (BAL) cells, and
      peripheral blood mononuclear cells (PBMC) of each macaque, RNA was isolated and
      the SIV env V1 region was amplified, cloned, and sequenced. Lung homogenates and
      BAL cells contained a more limited repertoire of viral genotypes than PBMC.
      SIV/17E-Fr was the major genotype in the lungs of 5 macaques and in BAL cells of
      6 macaques. The remainder of the macaques had SIV/17E-Fr and the macrophage
      tropic strains of SIV/DeltaB670 clones 2 and 12. In contrast, SIV/17E-Fr was the
      predominant strain in the PBMC of only 3 of 11 macaques. The viral strain that
      predominated in PBMC was rarely the strain that predominated in the lungs (only 3
      of 11 macaques). The severity of pulmonary lesions did not correlate with the
      levels of viral RNA in lung homogenates or in plasma. However, when only SIV/17E
      Fr was expressed in the lung, the viral load in the lung was significantly higher
      (P = 0.016) than when SIV/DeltaB670 was present alone or in combination with
      SIV/17E-Fr. These data suggest that SIV pneumonia is associated with selective
      replication of specific macrophage-tropic genotypes in the lung and that SIV/17E
      Fr has a selective advantage for replication in the lung.

PMID- 11531415
TI  - Adaptation to blockade of human immunodeficiency virus type 1 entry imposed by
      the anti-CCR5 monoclonal antibody 2D7.
AB  - The second extracellular loop (ECL2) domain of CC-chemokine receptor 5 (CCR5) has
      been proposed as a specific target site for therapeutic agents aimed at blocking
      CCR5-dependent entry by human immunodeficiency virus type I (HIV-1). We have
      adapted two CCR5-using HIV-1 isolates, prototypic JR-CSF, and a primary isolate,
      11-121, to replicate in vitro in the presence of high concentrations of a
      monoclonal antibody (MAb 2D7) specific for the CCR5 ECL2 domain. The 75%
      inhibitory concentrations (IC(75)) for the two 2D7-adapted isolates were
      approximately 100-fold higher than those for corresponding control isolates
      passaged without the MAb. Adapted isolates did not acquire the ability to use
      CXCR4, CCR3, or CCR1. Env clones derived from MAb 2D7-adapted JR-CSF showed
      several gp120 mutations that were not found in any of the control JR-CSF clones.
      The in vitro observations suggest that CCR5-using HIV-1 strains might also be
      able to adapt in vivo to evade an ECL2-blocking therapeutic agent.

PMID- 11531416
TI  - Sequence analysis of the Spodoptera litura multicapsid nucleopolyhedrovirus
      genome.
AB  - The complete Spodoptera litura multicapsid nucleopolyhedrovirus (SpltMNPV) genome
      contained 139,342 bp with a G+C content of 42.7%, and 141 putative open reading
      frames (ORFs) or genes of 150 nucleotides or greater that showed minimal overlap.
      Ninety-six ORFs had homologues in Autographa californica multicapsid
      nucleopolyhedrovirus (AcMNPV), 16 had homologues in other baculoviruses, and 29
      were unique to SpltMNPV. The homologues of ubiquitin and gp37 are fused in
      SpltMNPV. The genome lacked a homologue of the major budded virus glycoprotein
      gene gp64, but it contained a homologue of ORF130 of Lymantria dispar multicapsid
      nucleopolyhedrovirus (LdMNPV). There were two homologues of AcMNPV ORF2 (bro
      gene), and a DnaJ protein gene (SpltORF39) in which the N-terminus showed
      homologies with the J domain of DnaJ family proteins. Seventeen homologous
      regions (hrs) were identified, each containing 2-29 palindromic repeats, with an
      average length of 534 bp and base content (G+C%) of 33.0.

PMID- 11531417
TI  - Effect of influenza virus matrix protein and viral RNA on ribonucleoprotein
      formation and nuclear export.
AB  - The formation of influenza virus ribonucleoprotein (RNP) is a necessary step in
      viral assembly and maturation in infected cells, but the mechanism remains
      incompletely understood. Influenza virus proteins such as matrix (M1) and
      cellular proteins have been implicated in assembly and transport of RNP. To study
      the assembly of RNP and the translocation of RNP complexes in cells, RNPs were
      reconstituted from nucleoprotein (NP), M1, and viral RNA (vRNA) synthesized in
      vitro. The syntheses were accomplished using specific plasmids in a system
      coupling transcription and translation under the control of the T7 promoter. The
      density of the resulting RNP complexes was analyzed by glycerol gradient
      centrifugation and the morphology was examined by transmission electron
      microscopy. Protomers of NP self-assembled into circular oligomers regardless of
      the presence of vRNA or M1. However, helical structures similar in conformation
      and density to RNPs purified directly from influenza virus were formed only when
      M1 and vRNA were also present. In the absence of vRNA, no helical structures were
      formed from NP and M1. The plasmids also contained the CMV promoter, which
      permitted expression of M1, NP, and vRNA in Madin-Darby canine kidney (MDCK). M1
      and NP were both present in the cytoplasm of MDCK also expressing vRNA, but NP
      was retained in the nucleus of cells expressing M1 without vRNA. Our data
      demonstrate for the first time that vRNA and M1 together promote the self
      assembly of influenza virus NP into the quaternary helical structure typical of
      the viral RNP. The results also indicate that the interaction of NP with vRNA and
      M1 in a system devoid of other viral proteins can lead to translocation of RNP
      from nucleus to cytoplasm.

PMID- 11531418
TI  - Locus of a virus neutralization epitope on the Japanese encephalitis virus
      envelope protein determined by use of long PCR-based region-specific random
      mutagenesis.
AB  - We prepared recombinant Japanese encephalitis (JE) virus populations possessing
      random mutations at the envelope (E) protein region by a long PCR-based method.
      Neutralization-resistant mutants were selected from these populations by
      application of JE-specific virus neutralizing monoclonal antibody (mAb) 503,
      which possessed a 51,200-fold neutralization titer. We classified the mutants
      into three groups, each bearing two amino acid alterations at the E protein
      region: 52, Gln-Arg, and 136, Lys-Glu; 136, Lys-Glu, and 275, Ser-Pro; and 126,
      Ile-Thr, and 136, Lys-Glu, respectively. Three different genetically engineered
      variants, each bearing a single mutation, 126, Ile-Thr; 136, Lys-Glu; and 275,
      Ser-Pro, respectively, showed partial but not complete recovery of reactivity to
      mAb 503. Our results indicate that the amino acid substitutions at amino acid
      positions 52, 126, 136, and 275 altered the structure of the neutralization
      epitope for mAb 503 on the E protein. All these mutations were clustered at the
      junction of domains I and II of the E protein and it is likely that the epitope
      for mAb 503 is composed of at least E(0)-e, D(0)-a, and k strands of the E
      protein. We also demonstrated the efficacy of the long PCR-based recombinant
      virus technique as a useful tool for the creation of a variety of mutants bearing
      random mutations at targeted areas of the virus genome.

PMID- 11531419
TI  - Mechanisms of loss of foreign gene expression in recombinant vesicular stomatitis
      viruses.
AB  - We investigated the stability and mechanisms of loss of foreign gene expression
      in two recombinant vesicular stomatitis viruses (VSVs). A recombinant expressing
      the cellular CD4 protein exhibited remarkable stability of foreign gene
      expression. However, after 26 sequential passages, a mutant no longer expressing
      CD4 was recovered from the virus stock. Sequencing of the CD4 coding region in
      this mutant revealed a single nucleotide deletion causing a frameshift and
      termination of protein synthesis. A second VSV recombinant expressing the measles
      virus F protein grew poorly and exhibited extreme instability of expression of
      the F protein. Expression of F protein was lost rapidly through mutations of the
      upstream transcription termination site from (3')AUAC(5') to (3')AUAU(5'), as
      well as lengthening of the subsequent U(7) tract that is the template for poly(A)
      addition to VSV G mRNA. Such mutations resulted in fusion of the F mRNA to the 3'
      end of the G mRNA, making the F protein translation initiation codon
      inaccessible. We suggest that the VSV polymerase is error prone during
      replication of the U(7) tract, providing a rapid means for complete elimination
      of expression of proteins that are toxic to the virus life cycle.

PMID- 11531420
TI  - Antibodies that neutralize SIV(mac)251 in T lymphocytes cause interruption of the
      viral life cycle in macrophages by preventing nuclear import of viral DNA.
AB  - Previous reports from our lab had shown that sera obtained from SIV(mac)-infected
      animals neutralized SIV(mac) infectivity in CD4(+) T cells but failed to protect
      monkey primary macrophages from infection with the virus. However, the antibodies
      could inhibit completion of the viral life cycle in the macrophages at the
      postentry stage(s). In this report we examined the mechanisms of the late effect
      of the antibodies. Using monoclonal antibodies (MAbs), we demonstrated that only
      antibodies to the SIV envelope protein (KK17 and KK42) but not antibody to the
      viral core protein (FA2) had the same inhibitory effect as that of the anti-SIV
      sera. To identify the stage of the viral replication cycle that was inhibited by
      anti-SIV antibodies in macrophages, we used various PCR techniques to study viral
      entry/reverse transcription (by amplifying the viral gag gene), viral genome
      nuclear transport (by amplifying 2-LTR circular forms), viral integration (by Alu
      PCR assay), and viral protein expression (by RIPA). We found that in macrophage
      cultures inoculated with SIV(mac)251 that were preincubated with antienvelope
      MAbs, viral DNA was detected at 8 h postinoculation but the 2-LTR circular forms
      and integrated viral DNAs were undetectable, and viral proteins were not
      expressed in these infected macrophages. These results strongly suggested that
      anti-SIV antibodies inhibited SIV(mac) replication in macrophages by blocking
      nuclear transport of viral genomes since viral DNA could not be detected in the
      nuclei of treated cultures. Furthermore, we showed that although viral
      replication in macrophages was interrupted by the antibodies, when cocultured
      with permissive T cells, the viral genomes presented in the cytoplasm of the
      macrophages could readily transfer to T cells during cell-cell contact.
      Importantly, this transfer could not be prevented by the antibodies. These
      results might explain the failure of passive antibody immunization against
      SIV(mac)251--a critical obstacle in AIDS vaccine development.

PMID- 11531421
TI  - TNF-alpha-induced cell death in feline immunodeficiency virus-infected cells is
      mediated by the caspase cascade.
AB  - TNF-alpha induced apoptosis in a feline fibroblastic cell line (CRFK) infected
      with FIV but not in its uninfected control. In this study, to understand the
      molecular basis of the different susceptibilities to TNF-alpha between FIV
      infected and uninfected cells, we examined the expression of TNF receptors and
      the activation of the caspase and NF-kappaB pathways. Expression levels of TNFR I
      and TNFR II mRNAs were similar between uninfected and FIV-infected CRFK cells. To
      understand the role of caspases in TNF-alpha-induced apoptosis, we examined the
      effect of three different classes of caspase inhibitors, Z-VAD-FMK, Ac-YVAD-CMK,
      and Z-DEVD-FMK, on the TNF-alpha-induced apoptosis in FIV-infected cells.
      Pretreatment with each of these caspase inhibitors protected FIV-infected CRFK
      cells from TNF-alpha-induced cell death. Moreover, one of the caspase substrates,
      poly(ADP-ribose) polymerase, was shown to be cleaved after TNF-alpha treatment in
      FIV-infected CRFK cells but not in uninfected CRFK cells. Electrophoretic
      mobility shift assay using an NF-kappaB motif oligonucleotide and promoter assay
      using an NF-kappaB luciferase reporter construct indicated that TNF-alpha
      treatment had induced activation of NF-kappaB in both FIV-infected and uninfected
      CRFK cells. The present study indicates that TNF-alpha-induced apoptosis in FIV
      infected CRFK cells is mediated by the activation of the caspase cascade, but not
      by either upregulation of TNF receptor or inhibition of NF-kappaB.

PMID- 11531422
TI  - Fluorine encapsulation and stabilization of biologically relevant low-valence
      copper-oxo cores.

PMID- 11531423
TI  - Preparation of Cd(1-x)Zn(x)Se using microwave-assisted polyol synthesis.

PMID- 11531424
TI  - Phosphorous acid and arsenious acid as ligands.

PMID- 11531425
TI  - Thermal spin crossover in binuclear iron(II) helicates: negative cooperativity
      and a mixed spin state in solution.

PMID- 11531427
TI  - Syntheses, vibrational spectra, and theoretical studies of the adamantanoid
      Sn(4)Ch(10)(4-) (Ch = Se, Te) anions: X-ray crystal structures of [18-crown-6
      K](4)[Sn4Se10]*5en and [18-crown-6-K](4)[Sn4Te10]*3en*2THF.
AB  - The salts [18-crown-6-K](4)[Sn(4)Se(10)].5en and [18-crown-6
      K](4)[Sn(4)Te(10)].3en.2THF were isolated upon addition of THF to the
      ethylenediamine (en) extracts of the alloys KSn(0.90)Se(1.93) and K(4)Sn(4)Te(10)
      that had been extracted in the presence of 18-crown-6 (1,4,7,10,13,16
      hexaoxacyclooctadecane). The Sn(4)Te(10)(4-) anion has been structurally
      characterized for the first time by a single-crystal X-ray diffraction study of
      [18-crown-6-K](4)[Sn(4)Te(10)].3en.2THF: P2(1)/n, a = 22.420(5) A, b = 19.570(4)
      A, c = 24.680(5) A, beta = 96.90(3)(o), Z = 4, and R(1) = 0.0468 at -183 degrees
      C. In addition to Si(4)Te(10)(4-) and Ge(4)Te(10)(4-), the Sn(4)Te(10)(4-) anion
      represents the only other known group 14 adamantanoid telluride. The X-ray
      crystal structure determination of the related [18-crown-6-K](4)[Sn(4)Se(10)].5en
      salt has also been determined: P2(1)/n, a = 22.003(2) A, b = 18.966(2) A, c =
      24.393(2) A, beta = 97.548(8)(o), Z = 4, and R(1) = 0.0843 at -123 degrees C. The
      anion geometries are of the adamantanoid type where the Sn(IV) atoms occupy the
      bridgehead positions and the chalcogen atoms occupy the bridging and terminal
      sites. The energy minimized geometries of Sn(4)Ch(10)(4-) have also been
      determined using density functional theory (DFT). Mayer bond order analyses,
      Mayer valencies, and empirical bond valencies indicate that the terminal Sn-Ch
      bonds have significant multiple bond character, with the terminal Sn-Se bond
      having more multiple bond character than the terminal Sn-Te bond. The vibrational
      frequencies of the Sn(4)Se(10)(4-) and Sn(4)Te(10)(4-) anions have been
      calculated using DFT methods, allowing the Raman spectrum of Sn(4)Se(10)(4-) to
      be fully assigned.

PMID- 11531426
TI  - Synthesis, characterization, and activation of thermally stable mu-1,2
      peroxodiiron(III) complex.

PMID- 11531428
TI  - Synthesis and characterization of an Al(69)(3-) cluster with 51 naked Al atoms:
      analogies and differences to the previously characterized Al(77)(2-) cluster.
AB  - A disproportionation process of a metastable AlCl solution with a simultaneous
      ligand exchange-Cl is substituted by N(SiMe(3))(2)-leads to a
      [Al(69)[N(SiMe(3))(2)](18)](3-) cluster compound that can be regarded as an
      intermediate on the way to bulk metal formation. The cluster was characterized by
      an X-ray crystal structural analysis. Regarding its structure and the packing
      within the crystal, this metalloid cluster with 4 times more Al atoms than
      ligands is compared to the [Al(77)N(SiMe(3))(2)](20)](2-) cluster that has been
      published four years ago. Although there is a similar packing density of the Al
      atoms in both clusters as well as in Al metal, the X-ray structural analysis
      shows significant differences in topology and distance proportions. The
      differences between these-at a first glance almost identical-Al clusters
      demonstrate that results of physical measuring, e.g., of nanostructured surfaces
      which carry supposedly identical cluster species, have to be interpreted with
      great caution.

PMID- 11531429
TI  - Crystal structures and magnetic properties of new cyano-bridged two-dimensional
      grid-like bimetallic assemblies [Ni(tn)2]2[Cr(CN)5((NO)]OH*H2O and
      [NI(tn)2]2[Co(CN)6]NO3*2H2O (tn=1,3-propanediamine).
AB  - Two bimetallic assemblies, [Ni(tn)(2)](2)[Cr(CN)(5)(NO)]OH.H(2)O (1) and
      [Ni(tn)(2)](2)[Co(CN)(6)]NO(3).2H(2)O (2) (tn = 1,3-diaminopropane), have been
      prepared and structurally and magnetically characterized. Crystal data for 1 (2):
      space group P1 (P1), a = 8.698(3) (8.937(2)) A, b = 10.001(2) (9.863(1)) A, c =
      10.158(2) (10.064(1)) A, alpha = 87.40(2) (86.064(10)) degrees, beta = 65.10(2)
      (65.489(10)) degrees, gamma = 81.63(2) (81.572(12)) degrees and Z = 1 (1). Both
      structures consist of two-dimensional grid-like polycations containing Ni-N
      triple bond C-M linkages (M = Cr or Co) and counteranions (OH, NO(3)). Magnetic
      studies of 1 showed that the complex displays a metamagnetic behavior originating
      from intralayer ferromagnetic and interlayer antiferromagnetic interactions. Long
      range antiferromagnetic ordering was observed at T(N) = 3.3 K. Complex 2 exhibits
      intramolecular ferromagnetic interactions through the diamagnetic N triple bond C
      Co-N triple bond C bridges, owing to superexchange involving the empty d(sigma)
      orbital of the diamagnetic Co(III) ion.

PMID- 11531430
TI  - Alkyl and aryl substituted corroles. 1. Synthesis and characterization of free
      base and cobalt containing derivatives. x-ray structure of
      (Me(4)Ph(5)Cor)Co(py)(2).
AB  - The synthesis, spectroscopic properties, and electrochemistry of six different
      alkyl- and aryl-substituted Co(III) corroles are presented. The investigated
      compounds contain methyl, ethyl, phenyl, or substituted phenyl groups at the
      eight beta-positions of the corrole macrocycle and four derivatives also contain
      a phenyl group at the 10-meso position of the macrocycle. Each cobalt corrole
      undergoes four reversible oxidations in CH(2)Cl(2) containing 0.1 M tetra-n
      butylammonium perchlorate and exists as a dimer in its singly and doubly oxidized
      forms. The difference in potential between the first two oxidations is associated
      with the degree of interaction between the two corrole units of the dimer and
      ranges from an upper value of 0.62 V, in the case of (Me(6)Et(2)Cor)Co, to a
      lower value of about 0.17 V, in the case of four compounds which have a phenyl
      group located at the 10-meso position of the macrocycle. These Co(III) corroles
      strongly coordinate two pyridine molecules or one carbon monoxide molecule in
      CH(2)Cl(2) media, and ligand binding constants were evaluated using spectroscopic
      and electrochemical methods. The structure of (Me(4)Ph(5)Cor)Co(py)(2) was also
      determined by X-ray diffraction. Crystal data:
      (Me(4)Ph(5)Cor)Co(py)(2).3CH(2)Cl(2).H(2)O, orthorhombic, a = 19.5690(4) A, b =
      17.1070(6) A, c = 15.9160(6) A, V = 5328.2(5) A(3), space group Pna2(1), Z = 2,
      35 460 observations, R(F) = 0.069.

PMID- 11531431
TI  - Alkyl and aryl substituted corroles. 2. Synthesis and characterization of linked
      "face-to-face" biscorroles. X-ray structure of (BCA)Co(2)(py)(3), where BCA
      represents a biscorrole with an anthracenyl bridge.
AB  - The synthesis, spectroscopic properties, and electrochemistry of (BCA)Co(2) and
      (BCB)Co(2) are described where BCA and BCB represent biscorroles linked by an
      anthracenyl (A) or a biphenylenyl (B) bridge. The pyridine and CO binding
      properties of (BCA)Co(2) and (BCB)Co(2) are also presented, and one of the
      compounds in its pyridine-ligated form, (BCA)Co(2)(py)(3), is structurally
      characterized. The data on the biscorroles are compared on one hand to the
      monocorrole having the same substitution pattern and on the other hand to
      bisporphyrins having two Co(II) ions and the same anthracenyl or biphenylenyl
      linkers in order to better understand the interaction which occurs between the
      two corrole macrocycles. A parallel study on five different Co(III) phenyl
      substituted corroles showed that bis-pyridine and mono-CO adducts are readily
      formed from the complexes in CH(2)Cl(2). This present paper examines how the
      ligand binding properties and electrochemistry of these Co(III) corroles are
      modified by the anthracenyl or biphenylenyl bridge which links the two
      macrocycles in a face to face orientation. An X-ray crystal structure was
      obtained for the tris-pyridine adduct of the anthracenyl bridged derivative,
      (BCA)Co(2)(py)(3), and gives the following results:
      C(127)H(99)Co(2)N(11).2CHCl(3), M = 2135.90, triclinic, space group P&onemacr;, a
      = 13.2555(5) A, b = 18.6406(8) A, c = 22.2140(9) A, alpha = 94.186(9) degrees,
      beta = 102.273(9) degrees, gamma = 94.205(9) degrees, V = 5326.8(4) A(3), 9293
      independent reflections collected, R(F) = 0.066.

PMID- 11531432
TI  - Preparation, crystal structure, and properties of barium pernitride, BaN(2).
AB  - Stoichiometric barium pernitride, BaN(2), was prepared from the elements under
      N(2) pressure of 5600 bar in an autoclave at 920 K. The compound is isotypic to
      ThC(2) (space group C2/c, Z = 4) according to powder X-ray (neutron) diffraction
      data with a = 7.1712(1), b = 4.3946(1), c = 7.2362(1) A, and beta = 104.864(1)
      degrees (a = 7.1745(1), b = 4.3963(1), c = 7.2393(1) A, beta = 104.876(1) degrees
      ). The N-N distance of 1.221(4) A (based on the neutron diffraction data) is
      indicative of a double bond in the N(2)(2-) dumbbells. BaN(2) is metallic
      according to magnetic susceptibility measurements and TB-LMTO band structure
      calculations.

PMID- 11531433
TI  - Synthesis, structure, and properties of Cs(4)Th(4)P(4)Se(26): a quaternary
      thorium selenophosphate containing the (P(2)Se(9))(6-) anion.
AB  - Orange crystals of Cs(4)Th(4)P(4)Se(26) were grown from the reaction of (232)Th
      and P in a Cs(2)Se(3)/Se molten salt flux at 750 degrees C. Cs(4)Th(4)P(4)Se(26)
      crystallizes in the orthorhombic space group Pbca with the unit cell parameters:
      a = 12.0130(6), b = 14.5747(7), c = 27.134(1) A; Z = 8. The compound exhibits a
      three-dimensional structure, consisting of dimeric [Th(2)Se(13)] polyhedral
      units. The two crystallographically independent, nine-coordinate, bicapped
      trigonal prismatic thorium atoms share a triangular face to form the dimer, and
      each dimer edge-shares two selenium atoms with two other dimers to form kinked
      chains along the [010] direction. While this structure shares features of the
      previously reported Rb(4)U(4)P(4)Se(26), including phosphorus in the 5+ oxidation
      state, careful inspection of the structure reveals that the selenophosphate anion
      that knits the structure together in three directions in both compounds is a
      unique (P(2)Se(9))(6-) anion. The formula may be described best as
      [Cs(2)Th(2)(P(2)Se(9))(Se(2))(2)](2). The (P(2)Se(9))(6-) anion features a nearly
      linear Se-Se-Se backbone with an angle of 171 degrees and Se-Se distances that
      are approximately 0.2-0.3 A longer than the typical single Se-Se bond. Magnetic
      studies confirm that this phase contains Th(IV). Raman data for this compound is
      reported, and structural comparisons will be drawn to its uranium analogue,
      Rb(4)U(4)P(4)Se(26).

PMID- 11531434
TI  - Cyano-bridged bimetallic assemblies from hexacyanometalate, [M(CN)6](3-) (M =
      Mn(III) and Fe(III)), and [M(N4-macrocycle)]2+ (M=Fe(III), Ni(II) and Zn(II))
      building blocks. Syntheses, multidimensional structures, and magnetic properties.
AB  - Reactions between [M(N(4)-macrocycle)](2+) (M = Zn(II) and Ni(II); macrocycle
      ligands are either CTH = d,l-5,5,7,12,12,14-hexamethyl-1,4,8,11
      tetraazacyclotetradecane or cyclam = 1,4, 8, 11-tetrazaazaciclotetradecane) and
      [M(CN)(6)](3-) (M = Fe(III) and Mn(III)) give rise to cyano-bridged assemblies
      with 1D linear chain and 2D honeycomblike structures. The magnetic measurements
      on the 1D linear chain complex [Fe(cyclam)][Fe(CN)(6)].6H(2)O 1 points out its
      metamagnetic behavior, where the ferromagnetic interaction operates within the
      chain and the antiferromagnetic one between chains. The Neel temperature, T(N),
      is 5.5 K and the critical field at 2 K is 1 T. The unexpected ferromagnetic
      intrachain interaction can be rationalized on the basis of the axially elongated
      octahedral geometry of the low spin Fe(III) ion of the [Fe(cyclam)](3+) unit. The
      isostructural substitution of [Fe(CN)(6)](3-) by [Mn(CN)(6)](3-) in the
      previously reported complex [Ni(cyclam)](3)[Fe(CN)(6)](2).12H(2)O 2 leads to
      [Ni(cyclam)](3)[Mn(CN)(6)](2).16 H(2)O 3, which exhibits a corrugated 2D
      honeycomblike structure and a metamagnetic behavior with T(N) = 16 K and a
      critical field of 1 T. In the ferromagnetic phase (H > 1 T) this compound shows a
      very important coercitive field of 2900 G at 2 K. Compound
      [Ni(CTH)](3)[Fe(CN)(6)](2).13H(2)O 4, C(60)H(116)Fe(2)N(24)Ni(3)O(13),
      monoclinic, A 2/n, a = 20.462(7), b = 16.292(4), c = 27.262(7) A, beta =
      101.29(4) degrees, Z = 4, also has a corrugated 2D honeycomblike structure and a
      ferromagnetic intralayer interaction, but, in contrast to 2 and 3, does not
      exhibit any magnetic ordering. This fact is likely due to the increase of the
      interlayer separation in this compound. ([Zn(cyclam)Fe(CN)(6)Zn(cyclam)]
      [Zn(cyclam)Fe(CN)(6)].22H(2)O.EtOH) 5, C(44)H(122)Fe(2)N(24)O(23)Zn(3),
      monoclinic, A 2/n, a = 14.5474(11), b = 37.056(2), c = 14.7173(13) A, beta =
      93.94(1) degrees, Z = 4, presents an unique structure made of anionic linear
      chains containing alternating [Zn(cyclam)](2+) and [Fe(CN)(6)](3)(-) units and
      cationic trinuclear units [Zn(cyclam)Fe(CN)(6)Zn(cyclam)](+). Their magnetic
      properties agree well with those expected for two [Fe(CN)(6)](3-) units with spin
      orbit coupling effect of the low spin iron(III) ions.

PMID- 11531435
TI  - The [Ru(CN)5(pyS)](4-) complex, an efficient self-assembled monolayer for the
      cytochrome c heterogeneous electron transfer studies.
AB  - The organothiol 4-mercaptopyridine (pyS) has been used extensively as facilitator
      for the assessment of heterogeneous electron transfer reaction of cytochrome c
      (cyt c). Its efficiency, however, is strongly affected by the instability of the
      adlayer due to the C-S bond cleavage. The K(4)[Ru(CN)(5)(pyS)].3H(2)O complex was
      synthesized and characterized aiming its utilization as an inorganic self
      assembled monolayer (SAM) that would enhance the gold adlayer stability. The SAM
      formed by this complex onto gold (RupySAu) was characterized by spectroscopic
      (FTIRRAS and SERS) and electrochemical (LSV) techniques. The ex situ vibrational
      SERS and FTIRRAS spectra data of this SAM formed onto gold suggest a sigma
      interaction between the gold and sulfur atoms of the complex, inducing a
      perpendicular arrangement in relation to the surface normal. Additionally, SERS
      and FTIRRAS spectra performed for freshly prepared RupySAu adlayer and for large
      immersion times in the precursor solution have not shown any significant change
      that would reflect the degradation of the adlayer. The LSV desorption curves of
      this SAM indicate an enhancement in the C-S bond strength of the pyS ligand when
      coordinated to the [Ru(CN)(5)](3-) moiety. Comparatively to the data obtained for
      the desorption process of the pyS monolayer, the reductive desorption potential,
      E(rd), of the RupySAu presents a shift of -17 mV. This bond strength
      intensification leads to an increase in the stability of the monolayer. The
      voltammetric curves of cyt c carried out with the RupySAu electrode showed
      electrochemical parameters consistent with those reported for the native protein,
      as well as the maintenance of the electrochemical kinetic data after repetitive
      cycles. The results all together suggest that the pi back-bonding effect from the
      [Ru(CN)(5)](3-) metal center plays an important role in the stability of the
      RupySAu adlayer, improving the assessment of the cyt c heterogeneous electron
      transfer reaction.

PMID- 11531436
TI  - Artificial peptidase with an active site comprising a Cu(II) center and a
      proximal guanidinium ion. A carboxypeptidase A analogue.
AB  - An immobile artificial metallopeptidase having a well-defined active site was
      constructed on the backbone of cross-linked polystyrene by adjoining a
      guanidinium moiety to the Cu(II) complex of a tetraaza ligand. The catalyst
      (CABP) and intermediate polymers were characterized by elemental analysis, IR,
      inductively coupled plasma measurement, electron probe microanalysis, test for
      primary amines, binding of Cu(II) ion, and complexation of p-nitrobenzoate ion.
      CABP effectively catalyzed amide hydrolysis of carboxyl-containing N-acyl amino
      acids. The catalytic rate of CABP in the hydrolysis of unactivated amides was
      comparable to that of the catalytic antibody with the highest peptidase activity
      reported to date. It is proposed that the guanidinium moiety of CABP recognizes
      the carboxylate anion of the substrate whereas the Cu(II) center participates in
      the cleavage of the amide bond of the complexed substrate. Several characteristic
      features of carboxypeptidase A were reproduced by CABP: catalytic action of the
      metal ion, participation of guanidinium in substrate recognition, hydrolysis of
      small unactivated amides, and substrate selectivity toward amide bonds adjacent
      to a carboxylate group.

PMID- 11531437
TI  - Synthesis and characterization of the dimercury(I)-linked compound
      [PPn]4[(Re7C(CO)21Hg)2]. Oxidative cleavage of the mercury-mercury bond leading
      to carbidoheptarhenate complexes of mercury(II), including
      [PPN][Re7C(CO)21Hg(S=C(NME2)2)].
AB  - The reaction of [PPN](3)[Re(7)C(CO)(21)] with Hg(2)(NO(3))(2).2H(2)O in
      dichloromethane formed the complex [PPN](4)[(Re(7)C(CO)(21)Hg)(2)] ([PPN](4)[1]),
      isolated in 60% yield. Analogous salts of [1](4-) with [PPh(4)](+) and
      [NEt(4)](+) were also prepared. The crystal structure of [PPN](4)[1] showed that
      two carbidoheptarhenate cores are linked by a dimercury(I) unit (d(Hg-Hg) =
      2.610(4) A), with each individual mercury atom face-bridging. Oxidative cleavage
      of the Hg-Hg bond in [1](4-) was effected by 4-bromophenyl disulfide to form
      [Re(7)C(CO)(21)HgSC(6)H(4)Br](2-) ([4](2-)), by I(2) to form
      [Re(7)C(CO)(21)HgI](2-) ([5](2-)), and by Br(2) to form [Re(7)C(CO)(21)HgBr](2-)
      ([6](2-)). Oxidation of [1](4-) by ferrocenium ion (2 equiv) in the presence of
      tetramethylthiourea resulted in the derivative [Re(7)C(CO)(21)HgSC(NMe(2))(2)](-)
      ([7](-)). The molecular structure of [PPN][7] was determined by X-ray
      crystallography. This is the first example of a carbidoheptarhenate-mercury
      complex with a neutral ligand on mercury, and ligand exchange was demonstrated by
      displacement with triethylphosphine. Complex [7](-) can also be prepared by
      protonating [Re(7)C(CO)(21)HgO(2)CCH(3)](2-) in the presence of
      tetramethylthiourea. Cyclic voltammetry data to calibrate and compare the redox
      properties of compounds [1](4-) and [7](-) have been measured.

PMID- 11531438
TI  - Single-molecule magnets: preparation and properties of mixed-carboxylate
      complexes.
AB  - Methods are reported for the preparation of mixed-carboxylate versions of the
      [Mn(12)O(12)(O(2)CR)(16)(H(2)O)(4)] family of single-molecule magnets (SMMs).
      [Mn(12)O(12)(O(2)CCHCl(2))(8)(O(2)CCH(2)Bu(t))(8)(H(2)O)(3)] (5) and
      [Mn(12)O(12)(O(2)CHCl(2))(8)(O(2)CEt)(8)(H(2)O)(3)] (6) have been obtained from
      the 1:1 reaction of the corresponding homocarboxylate species. Complex
      5.CH(2)Cl(2).H(2)O crystallizes in the triclinic space group P1 with, at -165
      degrees C, a = 15.762(1), b = 16.246(1), c = 23.822(1) A, alpha = 103.92(1), beta
      = 104.50(1), gamma = 94.23(1) degrees, Z = 2, and V = 5674(2) A(3). Complex
      6.CH(2)Cl(2) crystallizes in the triclinic space group P1 with, at -158 degrees
      C, a = 13.4635(3), b = 13.5162(3), c = 23.2609(5) A, alpha = 84.9796(6), beta =
      89.0063(8), gamma = 86.2375(6) degrees, Z = 2, and V = 4207.3(3) A(3). Complexes
      5 and 6 both contain a [Mn(12)O(12)] core with the CHCl(2)CO(2-) ligands ordered
      in the axial positions and the RCO(2-) ligands (R = CH(2)Bu(t) (5) or Et (6)) in
      equatorial positions. There is, thus, a preference for the CHCl(2)CO(2-) to
      occupy the sites lying on the Mn(III) Jahn-Teller axes, and this is rationalized
      on the basis of the relative basicities of the carboxylate groups. Direct current
      magnetic susceptibility studies in a 10.0 kG field in the 2.00-300 K range
      indicate a large ground-state spin, and fitting of magnetization data collected
      in the 10.0-70.0 kG field and 1.80-4.00 K temperature range gave S = 10, g =
      1.89, and D = -0.65 K for 5, and S = 10, g = 1.83, and D = -0.60 K for 6. These
      values are typical of [Mn(12)O(12)(O(2)CR)(16)(H(2)O)(4)] complexes. Alternating
      current susceptibility studies show the out-of-phase susceptibility (chi(M)' ')
      signals characteristic of the slow relaxation in the millisecond time scale of
      single-molecule magnets. Arrhenius plots obtained from chi(M)' ' versus T data
      gave effective barriers to relaxation (U(eff)) of 71 and 72 K for 5 and 6,
      respectively. (1)H NMR spectra in CD(2)Cl(2) show that 5 and 6 are the main
      species present on dissolution, but there is evidence for some ligand
      distribution between axial and equatorial sites, by intra- and/or intermolecular
      exchange processes.

PMID- 11531439
TI  - Strong 1,4-P-O intramolecular interactions as a source of conformational
      preferences in alpha-stabilized phosphorus ylides.
AB  - For the first time, the existence of a strong intramolecular 1,4-interaction
      between the phosphorus atom and the oxygen atom in alpha-keto-stabilized ylides
      has been demonstrated by means of theoretical calculations. This interaction has
      a notable influence on the conformational preferences and rotational barriers of
      alpha-stabilized phosphorus ylides and bis-ylides.

PMID- 11531440
TI  - Highly efficient phosphodiester hydrolysis promoted by a dinuclear copper(II)
      complex.
AB  - The interaction of Cu(II) with the ligand tdci (1,3,5-trideoxy-1,3,5
      tris(dimethylamino)-cis-inositol) was studied both in the solid state and in
      solution. The complexes that were formed were also tested for phosphoesterase
      activity. The pentanuclear complex [Cu(5)(tdciH(
      2))(tdci)(2)(OH)(2)(NO(3))(2)](NO(3))(4).6H(2)O consists of two dinuclear units
      and one trinuclear unit, having two shared copper(II) ions. The metal centers
      within the pentanuclear structure have three distinct coordination environments.
      All five copper(II) ions are linked by hydroxo/alkoxo bridges forming a Cu(5)O(6)
      cage. The Cu-Cu separations of the bridged centers are between 2.916 and 3.782 A,
      while those of the nonbridged metal ions are 5.455-5.712 A. The solution
      equilibria in the Cu(II)-tdci system proved to be extremely complicated.
      Depending on the pH and metal-to-ligand ratio, several differently deprotonated
      mono-, di-, and trinuclear complexes are formed. Their presence in solution was
      supported by mass, CW, and pulse EPR spectroscopic study, too. In these
      complexes, the metal ions are presumed to occupy tridentate [O(ax),N(eq),O(ax)]
      coordination sites and the O-donors of tdci may serve as bridging units between
      two metal ions. Additionally, deprotonation of the metal-bound water molecules
      may occur. The dinuclear Cu(2)LH(-3) species, formed around pH 8.5, provides
      outstanding rate acceleration for the hydrolysis of the activated phosphodiester
      bis(4-nitrophenyl)phosphate (BNPP). The second-order rate constant of BNPP
      hydrolysis promoted by the dinuclear complex (T = 298 K) is 0.95 M(-1) s(-1),
      which is ca. 47600-fold higher than that of the hydroxide ion catalyzed
      hydrolysis (k(OH)). Its activity is selective for the phosphodiester, and the
      hydrolysis was proved to be catalytic. The proposed bifunctional mechanism of the
      hydrolysis includes double Lewis acid activation and intramolecular nucleophilic
      catalysis.

PMID- 11531441
TI  - Electronic communication in oligometallic complexes with ferrocene-based tris(1
      pyrazolyl)borate ligands.
AB  - Ferrocene-based tris(1-pyrazolyl)borate ligands 1R-Li and 1R-Tl have been
      synthesized and used to generate a variety of heterotrinuclear transition metal
      complexes, 3R-M [R = H, SiMe(3), cyclohexyl, (cyclohexyl)methyl, phenyl; M(II) =
      Mn, Fe, Co, Ni, Cu, Zn]. The poor solubility of 3H-M is greatly enhanced by the
      introduction of large organic substituents into the 4-positions of all pyrazolyl
      rings. The unsubstituted ligand 1H-Li and the trinuclear complex 3Cym-Cu [Cym =
      (cyclohexyl)methyl] have been investigated by X-ray crystallography. 1H-Li, which
      represents the first example of a structurally characterized lithium tris(1
      pyrazolyl)borate, forms centrosymmetric dimers in the solid state. A severe Jahn
      Teller distortion was observed for the (Bpz(3))(2)Cu fragment in 3Cym-Cu.
      Compared to the parent compounds [(HBpz(3))(2)M], the presence of uncharged
      ferrocenyl substituents in 3R-M tends to shift the M(2+)/M(3+) redox potential to
      significantly more cathodic values. The opposite is true if the ferrocenyl
      fragments are in their cationic state, which results in an anodic shift of the
      M(2+)/M(3+) transition. Most interestingly, the two ferrocenyl fragments in 3R-Cu
      appear to be electronically communicating.

PMID- 11531442
TI  - Molecular structures of edge-sharing square-planar dinuclear complexes with
      unsaturated bridges.
AB  - The dinuclear complexes of transition metal ions of type [M(2)(mu,eta(1)
      XY)(2)L(4)], where XY is an unsaturated ligand that can act as a four-electron or
      a two-electron donor through the X atom, appear in two molecular conformations
      depending on whether the coordination planes around the two metal atoms are
      coplanar or bent. In both structures the geometry of the X atom is planar,
      corresponding to an sp(2) hybridization. An ab initio theoretical study on 43
      representative complexes, complemented with a structural database analysis,
      provides a rationale for the experimentally observed structures.

PMID- 11531443
TI  - New synthetic and structural aspects in the chemistry of alkylaluminum fluorides.
      The mutual influence of hard and soft ligands and the hybridization as rigorous
      structural criterion.
AB  - A general synthetic strategy starting from metal alkyls is reported based on the
      hydrogen difluoride anion as a suitable reagent for obtaining organometallic
      fluorides. The newly prepared compounds are [Me(4)N][(i-Bu)(2)AlF(2)] (1),
      [Ph(4)P][(i-Bu)(2)AlF(2)] (2), and [Ph(4)P][AlF(4)] (3), containing the
      tetrahedral anions [(i-Bu)(2)AlF(2)](-) and [AlF(4)](-). The actual structures
      are prototypes that allowed a comparison of inorganic and organometallic
      fluorides in the frame of the hard and soft acid and base principle, by means of
      ab initio calculations. A new theoretical model is designed to put in equation
      form the qualitative statements of the Bent rule. The model allows the
      rationalization of the tendencies of bond angle variation in [R(2)MX(2)] systems
      containing a main group metal (M), in terms of hybridization of the central atom
      and the reciprocal influence of hard and soft ligands.

PMID- 11531444
TI  - A theoretical and experimental study on the Lewis acid-base adducts
      (P(4)E(3)).(BX(3)) (E = S, Se; X = Br, I) and (P(4)Se(3)).(NbCl(5)).
AB  - The Lewis acid-base adducts (P(4)E(3)).(BX(3)) (E = S, Se; X = Br, I) and
      (P(4)Se(3)).(NbCl(5)) have been prepared and characterized by Raman, IR, and
      solid-state (31)P MAS NMR spectroscopy. Hybrid density functional calculations
      (B3LYP) have been carried out for both the apical and the basal
      (P(4)E(3)).(BX(3)) (E = S, Se; X = Br, I) adducts. The thermodynamics of all
      considered species has been discussed. In accordance with solid-state (31)P MAS
      NMR and vibrational data, the X-ray powder diffraction structures of
      (P(4)S(3)).(BBr(3)) [monoclinic, space group P2(1)/m (No. 11), a = 8.8854(1) A, b
      = 10.6164(2) A, c = 6.3682(1) A, beta = 108.912(1) degrees, V = 568.29(2) A(3), Z
      = 2] and (P(4)S(3)).(BI(3)) [orthorhombic, space group Pnma (No. 62), a =
      12.5039(5) A, b = 11.3388(5) A, c = 8.9298(4) A, V = 1266.09(9) A(3), Z = 4]
      indicate the formation of an apical P(4)S(3) complex in the reaction of P(4)S(3)
      with BX(3) (X = Br, I). Basal adducts are formed when P(4)Se(3) is used as the
      donor species. Vibrational assignment for the normal modes of these adducts has
      been made on the basis of comparison between theoretically obtained and
      experimentally observed vibrational data.

PMID- 11531445
TI  - High-pressure pulse-radiolysis study of the formation and decomposition of
      complexes with iron-carbon sigma bonds: mechanistic comparison for different
      metal centers.
AB  - Volumes of activation for the formation and homolysis of the transient complexes
      (hedta)Fe(III)-CO(2)(2-) and (hedta)Fe(III)-CH(3)(-) (HOCH(2)CH(2)N(CH(2)CO(2
      ))CH(2)CH(2)N(CH(2)CO(2-))(2) = hedta) were determined using high-pressure pulse
      radiolysis techniques. A comparison of the results with those for analogous
      complexes with other central transition-metal cations (M(n+)) and ligands (L)
      points out that (i) the reaction of M(n)L(m) with aliphatic radicals (R(*))
      proceeds via an interchange ligand substitution mechanism, i.e. M(n)L(m) + R(*) -
      > L(m-1)M(n+1)-R + L, (ii) the homolysis of the metal-carbon bonds naturally
      follows the same mechanism, and (iii) the volume of activation for the homolysis
      reaction depends strongly on the nature of the central cation, i.e. larger for
      M(n+1) = Cr(III), Co(III), Ni(III) and smaller for Fe(III). The volume of
      activation for the reaction (hedta)Fe(III)-CO(2)(2-) + CO(2)(*-) + 2H(+) -->
      Fe(II)(hedta)(H(2)O)(-) + CO + CO(2) was measured, and the results enable a
      tentative proposal for the nature of the transition state of this interesting
      reaction.

PMID- 11531446
TI  - Verdoheme reactivity. Remarkable paramagnetically shifted (1)H NMR spectra of
      intermediates from the addition of hydroxide or methoxide with Fe(II) and Fe(III)
      verdohemes.
AB  - Studies of the reaction of 5-oxaporphyrin iron complexes (verdohemes) with
      methoxide ion or hydroxide ion have been undertaken to understand the initial
      step of ring opening of verdohemes. High-spin [ClFe(III)(OEOP)] undergoes a
      complex series of reactions upon treatment with hydroxide ion in chloroform, and
      similar species are also detected in dichloromethane, acetonitrile, and dimethyl
      sulfoxide. Three distinct paramagnetic intermediates have been identified by (1)H
      NMR spectroscopy. These reactive species are formed by addition of hydroxide to
      the macrocycle and to the iron as an axial ligand. Treatment of low-spin
      [(py)(2)Fe(II)(OEOP)]Cl (OEOP is the monoanion of octaethyl-5-oxaporphyrin) with
      excess methoxide ion in pyridine solution produces [(py)(n)()Fe(II)(OEBOMe)] (n =
      1 or 2) ((OEBOMe), dianion of octaethylmethoxybiliverdin), whose (1)H NMR
      spectrum undergoes marked alteration upon addition of further amounts of
      methoxide ion. An identical (1)H NMR spectrum, which is characterized by
      methylene resonances with both upfield and downfield paramagnetic shifts, is
      formed upon treatment of [Fe(II)(OEBOMe)](2) with methoxide in pyridine solution
      and results from the formation of [(MeO)Fe(II)(OEBOMe)](-).

PMID- 11531447
TI  - Oxonium ions from aqua regia: isolation by hydrogen bonding to crown ethers.
AB  - The preparation and structures of a variety of oxonium ion tetrachloroaurate(III)
      salts isolated from aqua regia are reported. The new compounds are
      [(H(5)O(2))(2)(12-crown-4)(2)][AuCl(4)](2) (1), [(H(7)O(3))(15-crown-5)][AuCl(4)]
      (2), [(H(5)O(2))(benzo-15-crown-5)(2)][AuCl(4)] (3), [(H(3)O)(18-crown
      6)][AuCl(4)] (4), [(H(5)O(2))(dibenzo-24-crown-8)][AuCl(4)] (5), [(H(5)O(2))(4
      nitrobenzo-15-crown-5)(2)][AuCl(4)] (6), [(H(3)O)(4-nitrobenzo-18-crown
      6)][AuCl(4)] (7), [(H(11)O(5))(tetrachlorodibenzo-18-crown-6)(2)][AuCl(4)] (8),
      and [(H(7)O(3))(dinitrodibenzo-30-crown-10)][AuCl(4)] (9). A significant
      correlation between the degree of proton hydration and crown ether size is
      observed. Aryl crown ethers are nitrated in concentrated aqua regia, but
      nonnitrated products may be obtained in a dilute solution of aqua regia by
      reaction with aqueous HAuCl(4).

PMID- 11531448
TI  - Synthesis, characterization, and photochemical properties of azobenzene
      conjugated Ru(II) and Rh(III) bis(terpyridine) complexes.
AB  - We synthesized azobenzene-conjugated bis(terpyridine) Ru(II) and Rh(III)
      mononuclear and dinuclear complexes and investigated their photochemical
      properties on excitation of the azo pi-pi band upon 366 nm light irradiation. The
      Ru mononuclear complex underwent trans-to-cis photoisomerization to reach the
      photostationary state with only 20% of the cis form, while the Ru dinuclear
      complex did not isomerize at all photochemically. On the other hand, the
      mononuclear and dinuclear Rh complexes showed almost complete trans-to-cis
      photoisomerization behavior. Cis forms of the Rh complexes thermally returned to
      the trans form at a much slower rate than those of organic azobenzenes, but they
      did not isomerize photochemically. The reduction potential of the cis forms was
      80 mV more negative than that of the trans forms. The photoisomerization quantum
      yields of the Rh complexes were strongly dependent on the polarity, viscosity,
      and donor site of the solvents as well as the size of the counterions. We
      investigated the photoisomerization process of these complexes using femtosecond
      absorption spectroscopy. For the Rh complexes, we observed S(n) <-- S(2) and S(n)
      <-- S(1) absorption bands similar to those of organic azobenzenes. For the Ru
      complexes, we observed very fast bleaching of the MLCT band of the Ru complex,
      which indicated that the energy transfer pathway to the MLCT was the primary
      cause of the depressed photoisomerization. The electronic structures, which were
      estimated from ZINDO molecular orbital calculation, supported the different
      photochemical reaction behavior between the Ru and Rh complexes.

PMID- 11531449
TI  - Structurally modulated magnetic properties in the A(3)MnRu(2)O(9) phases (A = Ba,
      Ca): the role of metal-metal bonding in perovskite-related oxides.
AB  - Ca(3)MnRu(2)O(9) and Ba(3)MnRu(2)O(9) were synthesized from transition metal
      dioxides and alkaline earth metal carbonates at 1100-1300 degrees C.
      Ca(3)MnRu(2)O(9) adopts the prototypical GdFeO(3)-type perovskite structure with
      Mn and Ru statistically disordered over the single metal atom site. The
      susceptibility shows Curie-Weiss behavior above 240 K with mu(eff) = 3.14
      micro(B)/metal atom, which is in excellent agreement with the expected spin-only
      moment of 3.20 micro(B). Below 150 K, the compound shows spin-glass-like short
      range ferrimagnetic correlations. The high-temperature region of the electrical
      resistivity reveals a small activation energy of 17(1) meV whereas the low
      temperature region is nonlinear and does not fit a variable range hopping model.
      Ba(3)MnRu(2)O(9) crystallizes in the 9-layer BaRuO(3)-type structure containing
      M(3)O(12) face-shared trioctahedral clusters in which Mn and Ru are statistically
      disordered. Ba(3)MnRu(2)O(9) shows nonlinear reciprocal susceptibility at all
      temperatures and is described by a variable-spin cluster model with an S =
      (1)/(2) ground state with thermally populated excited states. The low spin value
      of this system (S = (1)/(2)) is attributed to direct metal-metal bonding. Below
      30 K, the compound shows short-range magnetic correlations and spin-glass-like
      behavior. The high-temperature region of the electrical resistivity indicates a
      small activation energy of 8.8(1) meV whereas the low-temperature region is
      nonlinear. The importance of metal-metal bonding and the relationships to other
      related compounds are discussed.

PMID- 11531450
TI  - Hindered axial-equatorial carbonyl exchange in an Fe(CO)(4)(PR(3)) complex of a
      rigid bicyclic phosphine.
AB  - Variable-temperature (13)C NMR spectra for a series of Fe(CO)(4)(PR(3)) complexes
      ligated by phosphatri(3-methylindolyl)methane (1), phosphatri(pyrrolyl)methane
      (2), P(N-3-methylindolyl)(3) (3), and P(N-pyrrolyl)(3) (4) are reported. Ligand 2
      was prepared by reaction of tri(pyrrolyl)methane with PCl(3) in THF and Et(3)N.
      Compound 2 is stable to methanolysis, hydrolysis, and aerial oxidation at room
      temperature. Reactions of 2 with selenium powder and Rh(acac)(CO)(2) yield
      phosphatri(pyrrolyl)methane selenide (5) and Rh(acac)(CO)(2) (6), respectively.
      The carbonyl stretching frequency in the IR spectrum of 6 and the magnitude of
      (1)J(Se)(-)(P) in the (31)P NMR spectrum of 5 indicate that 2 is a strong pi-acid
      and a weak sigma-base, commensurate with its lack of reactivity with CH(3)I. The
      trend in the decreasing basicity of 2 and related phosphines and phosphites was
      determined to be P(NMe(2))(3) > 3 > 4 > 1 > P(OPh)(3) > 2. IR data for a series
      of Rh(acac)(CO)(PR(3)) complexes indicate the trend in decreasing pi-acceptor
      ability to be 2 approximately 1 > 4 > P(OPh)(3) > 3 > PPh(3). Phosphines 1-4 were
      reacted with Fe(2)(CO)(9) to yield Fe(CO)(4)(1) (7), Fe(CO)(4)(2) (8),
      Fe(CO)(4)(3) (9), and Fe(CO)(4)(4) (10), respectively. IR data for 7-10 support
      the trend in pi-acidity listed above. Variable-temperature (13)C NMR spectra for
      compounds 8-10 show a single doublet resonance for the carbonyls in the
      temperature range from -80 to 20 degrees C indicative of rapid intramolecular
      rearrangement of carbonyls between axial and equatorial sites. However, the (13)C
      NMR spectrum for 7 shows slowed axial-equatorial carbonyl exchange at 20 degrees
      C. The limiting slow-exchange spectrum is observed at -20 degrees C. Hindered
      carbonyl exchange in 7 is attributed to the rigid 3-fold symmetry and steric bulk
      of 1. In addition to characterization of the new compounds by NMR ((1)H, (13)C,
      and (31)P) spectroscopy, IR spectroscopy, mass spectrometry, and elemental
      analysis, compounds 2, 7, 9, and 10 were further characterized by X-ray
      crystallography.

PMID- 11531451
TI  - Tungsten oxo salicylate complexes from tungsten hexachloride reactions systems.
AB  - Tungsten hexachloride is a potent halogen-transfer agent, capable of reacting
      directly with salicylic acid to generate a tungsten oxo fragment and salicoyl
      chloride. As a result, oxo complexes dominate the chemistry of tungsten(VI)
      salicylates. Both mono- and disalicylate substituted tungsten oxo complexes are
      accessible. The Bronsted free acid W(=O)Cl(Hsal)(sal) complex is a sparingly
      soluble, presumably polymeric material that can be dissolved in THF. The THF
      adduct has been characterized by NMR spectroscopy, although an X-ray
      crystallographic study indicates that the product cocrystallizes with a
      structurally analogous d(1) WCl(2)(Hsal.THF)(sal) byproduct. The remaining
      chloride ligand in W(=O)Cl(Hsal)(sal) is replaced by a bridging oxo unit when the
      reaction contains a significant excess of salicylic acid. The product "linear"
      oxo bridged ditungsten complex, [W(=O)(Hsal)(sal)](2)O, forms intramolecular
      hydrogen bonds, accounting for its high solubility in noncoordinating solvents.
      An X-ray study shows that the intramolecular Hsal.sal hydrogen bonding in this
      complex accommodates a more linear W-O-W arrangement than does a previously
      observed class of isostructural diolate derivatives. Tungsten oxo tetrachloride,
      formed in the initial reaction between salicylic acid and WCl(6), also reacts
      with the salicoyl chloride byproduct to generate tungsten salicoylate (OAr-2
      COCl) complexes.

PMID- 11531453
TI  - Zinc diphosphonates templated by organic amines: syntheses and characterizations
      of [NH3(CH2)2NH3]Zn(hedpH2)2*2H2O and [NH3(CH2)nNH3(CH2)nNH3]Zn2(hedpH)2*2H2O
      (n=4,5,6) (hedp=1-hydroxyethylidenediphophonate).
AB  - Four new zinc diphosphonate compounds with formulas
      [NH(3)(CH(2))(2)NH(3)]Zn(hedpH(2))(2).2H(2)O, 1,
      [NH(3)(CH(2))(n)()NH(3)]Zn(2)(hedpH)(2).2H(2)O, (n = 4, 2; n = 5, 3; n = 6, 4)
      (hedp = 1-hydroxyethylidenediphosphonate) have been synthesized under
      hydrothermal conditions at 110 degrees C and in the presence of alkylenediamines
      NH(2)(CH(2))(n)()NH(2) (n = 2, 4, 5, 6). Crystallographic data for 1: monoclinic,
      space group C2/c, a = 24.7422(15), b = 5.2889(2), c = 16.0338(2) A, beta =
      117.903(1) degrees, V = 1856.17(18) A(3), Z = 4; 2: monoclinic, space group
      P2(1)/n, a = 5.4970(3), b = 12.1041(6), c = 16.2814(12) A, beta = 98.619(5)
      degrees, V = 1071.07(11) A(3), Z = 2; 3: monoclinic, space group P2(1)/n, a =
      5.5251(2), b = 12.5968(3), c = 16.1705(5) A, beta = 99.182(1) degrees, V =
      1111.02(6) A(3), Z = 2; 4: triclinic, space group P-1, a = 5.4785(2), b =
      14.1940(5), c = 16.0682(6) A, alpha = 81.982(2) degrees, beta = 89.435(2)
      degrees, gamma = 79.679(2) degrees, V = 1217.11(8) A(3), Z = 2. In compound 1,
      two of the phosphonate oxygens are protonated. The metal ions are bridged by the
      hedpH(2)(2-) groups through three of the remaining four phosphonate oxygens,
      forming a one-dimensional infinite chain. The protonated ethylenediamines locate
      between the chains in the lattice. In compounds 2-4, only one phosphonate oxygen
      is protonated. Compounds 2 and 3 have a similar three-dimensional open-network
      structure composed of [Zn(2)(hedpH)(2)](n) double chains with strong hydrogen
      bonding interactions between them, thus generating channels along the [100]
      direction. The protonated diamines and water molecules reside in the channels.
      Compound 4 contains two types of [Zn(2)(hedpH)(2)](n) double chains which are
      held together by strong hydrogen bonds, forming a two-dimensional network. The
      interlayer spaces are occupied by the [NH(3)(CH(2))(6)NH(3)](2+) cations and
      water molecules. The significant difference between structures 2-4 is also
      featured by the coordination geometries of the zinc atoms. The geometries of
      those in 2 can be described as distorted octahedral, and those in 3 as distorted
      square pyramidal. In 4, two independent zinc atoms are found, each with a
      distorted octahedral and a tetrahedral geometry, respectively.

PMID- 11531452
TI  - A DNA oligonucleotide-hemin complex cleaves t-butyl hydroperoxide through a
      homolytic mechanism.
AB  - Both electron paramagnetic resonance (EPR) and electronic absorption spectroscopy
      have been employed to investigate the reaction of a guanine-rich DNA nucleotide
      hemin complex (PS2.M-hemin complex) and organic peroxide (t-Bu-OOH). Incubation
      of the PS2.M-hemin complex with t-Bu-OOH resulted in the time-dependent decrease
      in the heme Soret with concomitant changes to the visible bands of the electronic
      absorbance spectrum for the PS2.M-hemin complex. Parallel EPR studies using the
      spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO) combined with spectral
      simulation demonstrated the presence of tert-butyloxyl, carbon-centered methyl,
      and methyl peroxyl radicals as well as a simple nitroxide (triplet) signal.
      Experiments, performed by maintaining a constant ratio of t-Bu-OOH/PS2.M-hemin
      complex ( approximately 35 mol/mol) while varying DMPO concentration, indicated
      that the relative contributions of each radical adduct to the composite EPR
      spectrum were significantly influenced by the DMPO concentration. For example, at
      DMPO/PS2.M-hemin of 10-50 mol/mol, a complex mixture of radicals was consistently
      detected, whereas at high trapping efficiency (i.e., DMPO/PS2.M-hemin of
      approximately 250 mol/mol) the tert-butyloxyl-DMPO adduct was predominant. In
      contrast, at relatively low DMPO/PS2.M-hemin complex ratios of < or =5 mol/mol, a
      simple nitroxide three-line EPR signal was detected largely in the absence of all
      other radicals. Together, these data indicate that tert-butyloxyl radical is the
      primary radical likely formed from the homolytic cleavage of the O-O peroxy bond
      of t-Bu-OOH, while methyl and methyl peroxyl radicals result from beta-scission
      of the primary tert-butyloxyl radical product.

PMID- 11531454
TI  - Hydridotris(thioxotriazolyl)borate (Tt), an ambidentate (N(3)/S(3)) tripodal
      ligand. X-ray crystal structures of sodium, bismuth(III), tin(IV), and
      manganese(I) complexes.
AB  - Treatment of the heterocycle 5-thioxo-4,5-dihydro-3,4-dimethyl-1,2,4-triazole
      (thioxotriazole) with sodium tetrahydroborate at 210 degrees C provides the new
      [N(3)/S(3)] ambidentate tripod ligand hydridotris(thioxotriazolyl)borate (Tt) as
      its sodium complex salt. Complexes of this ligand with sodium, bismuth(III),
      tin(IV), and manganese(I) have been synthesized and characterized by X-ray
      crystallography. The structures of these complexes illustrate the ambidentate
      character of the ligand with the softer metals bismuth and tin exhibiting sulfur
      coordination, while sodium and manganese(I) bond via the ligand nitrogen donors.
      In the [S(3)] coordination mode the ligand creates eight-membered chelate rings
      with the metal with the consequence that the metal ligand unit adopts a propeller
      type conformation with C(3)-symmetry. However, in the [N(3)] mode six-membered
      chelate rings are formed analogous to the familiar hydrotris(pyrazolyl)borate
      (Tp) ligand.

PMID- 11531455
TI  - Separating the racemic and meso diastereomers of a binucleating tetraphosphine
      ligand system through the use of nickel chloride.
AB  - The reaction of a 1:1 mixture of rac- and meso-et,ph-P4 (et,ph-P4 =
      (Et(2)PCH(2)CH(2))(Ph)PCH(2)P(Ph)CH(2)CH(2)PEt(2)) with 2 equiv of NiCl(2).6H(2)O
      in EtOH produces soluble rac-Ni(2)Cl(4)(et,ph-P4) and precipitates meso
      Ni(2)Cl(4)(et,ph-P4), allowing facile isolation of each bimetallic complex.
      Subsequent reaction with more than 250 equiv of NaCN in H(2)O/MeOH releases the
      et,ph-P4 ligand and [Ni(CN)(4)](2-). The rac,trans- and meso,trans
      Ni(CN)(2)(eta(2.5)-et,ph-P4) form as intermediates in the cyanolysis of rac- and
      meso-Ni(2)Cl(4)(et,ph-P4). These have been characterized by X-ray
      crystallography. The unusual partial isomerization of the meso- to rac-et,ph-P4
      ligand via the monometallic trans-Ni(CN)(2)(eta(2.5)-et,ph-P4) intermediate
      complex is discussed.

PMID- 11531456
TI  - Aromatic character of deltahedral borane dianions revisited.

PMID- 11531457
TI  - Interaction of [Ru(dmp)2(dppz)]2+ and [Ru(dmb)2(dppz)]2+ with DNA: effects of the
      ancillary ligands on the DNA-binding behaviors.

PMID- 11531458
TI  - Three-coordinate zinc amide and phenoxide complexes supported by a bulky Schiff
      base ligand.

PMID- 11531459
TI  - Conversational characteristics of children with fragile X syndrome: tangential
      language.
AB  - The production of tangential language during conversations was studied with
      people who have fragile X syndrome, autistic disorder, or mental retardation not
      caused by fragile X. Tangential language was found to be more prevalent among
      those with fragile X, compared to the control groups, especially within
      unsolicited comments. These results support our hypothesis that the tangential
      language seen in fragile X is not the result of either general developmental
      delay or undiagnosed autistic disorder. We offer a possible interpretation of
      these results based upon such phenotypic characteristics as social anxiety,
      hypersensitivity to social and sensory stimuli, and inhibitory control deficits.

PMID- 11531460
TI  - Quality and costs of supported living residences and group homes in the United
      Kingdom.
AB  - Information was collected on 63 adults in supported living residences, 55 adults
      in small group homes, and 152 adults in large group homes. Results indicated that
      (a) there were no statistically significant differences in service costs once
      these had been adjusted to take account of participant characteristics; (b)
      compared with participants living in small group homes, those in supported living
      residences had greater choice, participated in more community-based activities,
      experienced fewer scheduled activities, were more likely to have had their home
      vandalized, and were considered at greater risk of exploitation; (c) compared
      with participants living in large group homes, those in small group homes had
      larger social networks, more people in their social networks who were not staff,
      not family, and did not have mental retardation. These residents were considered
      at less risk of abuse.

PMID- 11531461
TI  - Diagnostic overshadowing reviewed and reconsidered.
AB  - Diagnostic overshadowing is a robust bias negatively affecting the accuracy of
      clinicians' judgments about concomitant mental illness in persons with mental
      retardation and mental illness. Reviewing 12 studies, we examined moderators of
      diagnostic overshadowing. Most client and clinician-based demographic variables
      have had limited usefulness. However, clinicians' cognitive complexity has been
      found to negatively affect overshadowing. Causal mechanisms of overshadowing
      remain largely unexplored, and diagnostic overshadowing has yet to be empirically
      demonstrated outside a single methodological approach. Areas needing further
      research are discussed and the recommendation made that researchers (a) better
      specify clinical decisions composing overshadowing, (b) attend to the type of
      processes by which diagnostic overshadowing occurs, (c) increase appreciation of
      environmental or situational variables related to overshadowing, and (d) engage
      in more comprehensive exploration of overshadowing using qualitative and other
      diverse methodologies.

PMID- 11531462
TI  - Staff members' prediction of consequences for their work in residential settings.
AB  - Staff members supporting people with mental retardation in residential care were
      given scenarios describing tasks they might carry out and asked what would happen
      if they did, or failed to do, them (i.e., who would notice, what would their
      reaction be). Only a minority reported strong, certain consequences for anything
      they did from residents, families, or external professionals. Although a majority
      reported consequences from managers or coworkers, a large minority did not. The
      tasks for which most staff members reported consequences were administration,
      followed by enabling residents. Results suggest that staff members who give
      priority to administration may be responding to the contingencies established by
      their managers and that a shift in priorities may be required to improve staff
      members' interactions with clients.

PMID- 11531463
TI  - Coping, burnout, and emotion in staff working in community services for people
      with challenging behaviors.
AB  - Staff in mental retardation services identify challenging behavior as a
      significant source of work-related stress. However, there has been little
      examination of the psychological processes that may explain an association
      between challenging behavior and staff stress. In the present study, direct-care
      staff (N = 83) from five community services completed a questionnaire on their
      emotional reactions to aggressive behavior, the coping strategies that they
      employ, and their experience of burnout. Staff more frequently reported using
      adaptive strategies than maladaptive ones to cope with aggressive behavior.
      Regression analyses showed that staff disengagement and adaptive coping
      strategies and their emotional reactions to aggressive behavior predicted burnout
      scores. Implications of these results for future research and for staff mental
      health are discussed.

PMID- 11531464
TI  - Evaluating the functional utility of congregate day treatment activities for
      adults with severe disabilities.
AB  - Many adults with severe disabilities spend considerable amounts of time in
      segregated day programs. We evaluated the degree to which these programs support
      purposeful and age-appropriate activity. Observations in 100 congregate community
      and institutional program sites indicated that approximately half of consumer
      time was spent in purposeful activity, 75% of which was age-appropriate. In 20%
      of the sites, though, most activity was age-inappropriate. These results, which
      were similar across community and institutional settings, are discussed in terms
      of respective program administrators evaluating their supports through
      comparisons with activity involvement in other programs and the need for changes
      in programs providing primarily age-inappropriate activities.

PMID- 11531465
TI  - Analysis of ankle kinetics during walking in individuals with Down syndrome.
AB  - The biomechanical characteristics of the ankle during gait of 17 participants
      with Down syndrome, ages 8 to 36 years, were investigated. Ten volunteers without
      disabilities of comparable anthropometric parameters were the control group. A 3
      dimensional gait analysis was performed using an optoelectronic system equipped
      with a force platform. Participants with Down syndrome showed significant
      decreases of plantar-flexor moments and of A1 and A2 joint powers. Furthermore,
      correlation between kinetic and temporal spatial parameters was markedly reduced
      or weak in comparison to the control group. These results point out a
      hypofunctioning of ankle, probably due to hypotonia and ligament laxity.

PMID- 11531466
TI  - Localization on short-range potentials in dissipative quantum mechanics.
AB  - In this Letter, the problem of the existence of a state localized on a weak short
      range attractive potential in the presence of dissipation is considered. It is
      shown that, contrary to the pure quantum case, a localized state is produced in
      any number of dimensions, while in low dimensions dissipation leads to much
      stronger localization. The results have physical implications for the dissipative
      dynamics of objects such as heavy particles in Fermi liquids and for
      superconductivity in high- T(c) materials.

PMID- 11531467
TI  - Vortices in trapped superfluid fermi gases.
AB  - We consider a superfluid of trapped fermionic atoms and study the single vortex
      solution in the Ginzburg-Landau regime. We define simple analytical estimates for
      the main characteristics of the system, such as the vortex core size, temperature
      regimes for the existence of a vortex, and the effects of rotation and
      interactions with normal fermions. The parameter dependence of the vortex core
      size (healing length) is found to be essentially different from that of the
      healing length in metallic superconductors or in trapped atomic Bose-Einstein
      condensation in the Thomas-Fermi limit. This is an indication of the importance
      of the confining geometry for the properties of fermionic superfluids.

PMID- 11531468
TI  - Superfluidity versus Bloch oscillations in confined atomic gases.
AB  - We study the superfluid properties of (quasi) one-dimensional bosonic atom
      gases/liquids in traps with finite geometries in the presence of strong quantum
      fluctuations. Driving the condensate with a moving defect we find the nucleation
      rate for phase slips using instanton techniques. While phase slips are quenched
      in a ring resulting in a superfluid response, they proliferate in a tube geometry
      where we find Bloch oscillations in the chemical potential. These Bloch
      oscillations describe the individual tunneling of atoms through the defect and
      thus are a consequence of particle quantization.

PMID- 11531469
TI  - Finite-temperature simulations of the scissors mode in Bose-Einstein condensed
      gases.
AB  - The dynamics of a trapped Bose-condensed gas at finite temperatures is described
      by a generalized Gross-Pitaevskii equation for the condensate order parameter and
      a semiclassical kinetic equation for the thermal cloud, solved using N-body
      simulations. The two components are coupled by mean fields as well as collisional
      processes that transfer atoms between the two. We use this scheme to investigate
      scissors modes in anisotropic traps as a function of temperature. Frequency
      shifts and damping rates of the condensate mode are extracted, and are found to
      be in good agreement with recent experiments.

PMID- 11531470
TI  - Inadequacy of the usual Galilean transformation in quantum mechanics.
AB  - We show that the superselection rule in the Galilean transformation, forbidding
      the superposition of states of different mass, in inconsistent with the
      nonrelativistic limit of the Lorentz transformation. We also point out that the
      extra Galilean phase is merely the residue of the "twin-paradox" effect, which
      does not vanish nonrelativistically. In general, there are phase effects due to
      proper time differences, and effects due to mass-energy equivalence, that do not
      vanish nonrelativistically but that are not handled adequately by the Galilean
      transformation.

PMID- 11531471
TI  - Cosmic microwave background polarization signals from tangled magnetic fields.
AB  - Tangled, primordial cosmic magnetic fields create small rotational velocity
      perturbations on the last scattering surface of the cosmic microwave background
      radiation. For fields which redshift to a present value of B0 = 3 x 10(-9) G,
      these vector modes are shown to generate polarization anisotropies of order 0.1-4
      microK on small angular scales (500<l<2000), assuming delta function or a power
      law spectra with n = -1. About 200 times larger signals result for n = 2 spectra.
      Unlike inflation generated, scalar modes, these signals are dominated by the odd
      parity, B-type polarization, which could help in their detection.

PMID- 11531474
TI  - Ratios of charged antiparticles-to-particles near mid-rapidity in Au + Au
      collisions at sqrt[s(NN)]=130 GeV.
AB  - We have measured the ratios of antiparticles to particles for charged pions,
      kaons, and protons near mid-rapidity in central Au+Au collisions at sqrt[s(NN)] =
      130 GeV. We observe <pi(-)>/<pi(+)> = 1.00+/-0.01(stat)+/-0.02(syst), <K->/<K+> =
      0.91+/-0.07(stat)+/-0.06(syst), and <p>/<p> = 0.60+/-0.04(stat)+/-0.06(syst). The
      <K->/<K+> and <p>/<p> ratios give a consistent estimate of the baryo-chemical
      potential mu(B) of 45 MeV, a factor of 5-6 smaller than in central Pb+Pb
      collisions at sqrt[s(NN)] = 17.2 GeV.

PMID- 11531476
TI  - Charged-particle pseudorapidity density distributions from Au+Au collisions at
      sqrt[s(NN)]=130 GeV.
AB  - The charged-particle pseudorapidity density dN(ch)/d eta has been measured for
      Au+Au collisions at sqrt[s(NN)] = 130 GeV at RHIC, using the PHOBOS apparatus.
      The total number of charged particles produced for the 3% most-central Au+Au
      collisions for /eta/<or=5.4 is found to be 4200+/-470. The evolution of dN(ch)/d
      eta with centrality is discussed, and compared to model calculations and to data
      from proton-induced collisions. The data show an enhancement in charged-particle
      production at midrapidity, while in the fragmentation regions, the results are
      consistent with expectations from pp and pA scattering.

PMID- 11531478
TI  - Even-harmonic generation due to beyond-Born-Oppenheimer dynamics.
AB  - We calculate the harmonic spectrum generated by a model HD molecule in a strong
      laser pulse. The unequal nuclear masses lead to the emission of even harmonics,
      i.e., photon frequencies which are even multiples of the laser frequency. The
      effect does not occur within the Born-Oppenheimer approximation. In the high
      frequency region, the even harmonics are almost of the same order of magnitude as
      the odd ones.

PMID- 11531472
TI  - Measurement of branching fractions for B --> pipi, Kpi, and KK decays.

PMID- 11531475
TI  - Measurement of the high energy two-body deuteron photodisintegration differential
      cross section.
AB  - The first measurements of the d(gamma,p)n differential cross section at forward
      angles and photon energies above 4 GeV were performed at the Thomas Jefferson
      National Accelerator Facility (JLab). The results indicate evidence of an angular
      dependent scaling threshold. Results at straight theta(cm) = 37 degrees are
      consistent with the constituent counting rules for E(gamma) greater, similar 4
      GeV, while those at 70 degrees are consistent with the constituent counting rules
      for E(gamma) greater, similar 1.5 GeV.

PMID- 11531477
TI  - Possibility to deduce the emission time sequence of neutrons and protons from the
      neutron-proton correlation function.
AB  - Experimental information has been derived from the neutron-proton correlation
      function in order to deduce the time sequence of neutrons and protons emitted at
      45 degrees in the E/A = 45 MeV 58Ni + 27Al reaction.

PMID- 11531479
TI  - Angle-resolved second-harmonic light scattering from colloidal particles.
AB  - We report angle-resolved second-harmonic generation (SHG) measurements from
      suspensions of centrosymmetric micron-size polystyrene spheres with surface
      adsorbed dye (malachite green). The second-harmonic scattering profiles differ
      qualitatively from linear light scattering profiles of the same particles. We
      investigated these radiation patterns using several polarization configurations
      and particle diameters. We introduce a simple Rayleigh-Gans-Debye model to
      account for the SHG scattering anisotropy. The model compares favorably with our
      experimental data. Our measurements suggest scattering anisotropy may be used to
      isolate particle nonlinear optics from other bulk nonlinear optical effects in
      suspension.

PMID- 11531480
TI  - Transverse instability of vector solitons and generation of dipole arrays.
AB  - We develop a theory of modulational instability of multiparameter solitary waves
      and analyze the transverse instability of composite (or vector) optical solitons
      in a saturable nonlinear medium. We demonstrate theoretically and experimentally
      that a soliton stripe breaks up into an array of ( 2+1)-dimensional dipole-mode
      vector solitons, thus confirming the robust nature of those solitons as
      fundamental composite structures of incoherently coupled fields.

PMID- 11531481
TI  - Universality of velocity gradients in forced Burgers turbulence.
AB  - We demonstrate that Burgers turbulence subject to large-scale white-noise-in-time
      random forcing has a universal power-law tail with exponent -7/2 in the
      probability density function of negative velocity gradients, as predicted by E,
      Khanin, Mazel, and Sinai [Phys. Rev. Lett. 78, 1904 (1997)]. A particle and shock
      tracking numerical method gives about five decades of scaling. Using a Lagrangian
      approach, the -7/2 law is related to the shape of the unstable manifold
      associated to the global minimizer.

PMID- 11531482
TI  - Production of Alfven waves by a rapidly expanding dense plasma.
AB  - The expansion of a dense (initially, n(lpp)/n(0)>>1) laser-produced plasma into
      an ambient magnetized plasma ( n(0) = 2 x 10(12) cm(-3)) capable of supporting
      Alfven waves has been studied. The interaction results in the production of shear
      Alfven waves as well as large density perturbations (Delta n/n(0) approximately
      0.3) associated with the moving dense plasma. The waves propagate away from the
      target and are observed to become plasma-column resonances. Spatial patterns of
      the wave magnetic fields are measured and are used to estimate the coupling
      efficiency of the laser energy and the kinetic energy of the dense plasma into
      wave energy.

PMID- 11531483
TI  - Evidence for droplet reorientation and interfacial charges in a polymer-dispersed
      liquid-crystal cell.
AB  - We observe a new feature ( plateau), sandwiched between two exponentially
      decaying components, in the switching response of a polymer-dispersed liquid
      crystal (PDLC) cell. Upon application of square-wave electrical pulses, the cell
      response exhibits a complex decay whose characteristics are significantly
      different within and outside the applied field. We interpret these results in
      terms of reorientation dynamics of nonspherical droplets in the PDLC. Irradiation
      of the PDLC with gamma rays induces significant changes in the cell response in a
      manner that is consistent with redistribution of charges at the liquid-crystal
      polymer interface in the PDLC.

PMID- 11531484
TI  - Dynamical event during slow crack propagation.
AB  - We address the role of material heterogeneities on the propagation of a slow
      rupture at laboratory scale. With a high speed camera, we follow an in-plane
      crack front during its propagation through a transparent heterogeneous Plexiglas
      block. We obtain two major results. First, the slip along the interface is
      strongly correlated over scales much larger than the asperity sizes. Second, the
      dynamics is scale dependent. Locally, mechanical instabilities are triggered
      during asperity depinning and propagate along the front. The intermittent
      behavior at the asperity scale is in contrast with the large scale smooth
      creeping evolution of the average crack position. The dynamics is described on
      the basis of a Family-Vicsek scaling.

PMID- 11531485
TI  - Hydrogen above saturation at silicon vacancies: H-pair reservoirs and
      metastability sites.
AB  - We propose that hydrogen-passivated multivacancies which appear to be fully
      saturated with H can actually capture additional H in electrically inactive
      sites. In silicon, first-principles total energy calculations show that splitting
      an (m>or=2) multivacancy into a mono- and an (m-1) vacancy provides a low-strain
      pairing site for H, 0.4 eV per H lower than any known bulk pairing site. This
      monovacancy ejection mechanism is an excellent candidate for the H reservoir
      found both in crystalline and amorphous Si. A distinct H pairing on the fully
      saturated m vacancies, by forming an internal surface Si-Si dimer, provides the
      final state of light-induced metastable degradation of hydrogenated amorphous
      silicon.

PMID- 11531486
TI  - Retention of the potential energy of multiply charged argon ions incident on
      copper.
AB  - The retained fraction of the potential energy of argon ions incident on copper
      has been measured using stationary calorimetry at charge states up to 9+ and
      kinetic energies ranging from 75 to 240 eV per ionic charge. An average fraction
      of 30% to 40% is found with little dependence on the charge number and on the
      kinetic energy. The retention of the total energy ranges from 60% to 75% and can
      mainly be accounted for by the retained fraction of the potential energy and the
      collisional energy lost by reflected ions and sputtered target atoms.

PMID- 11531487
TI  - Liquid-liquid phase transitions of phosphorus via constant-pressure first
      principles molecular dynamics simulations.
AB  - Pressure-induced phase transitions in liquid phosphorus have been studied by
      constant-pressure first-principles molecular dynamics simulations. By compressing
      a low-pressure liquid which consists of the tetrahedral P4 molecules, a
      structural phase transition from the molecular to polymeric liquid (a high
      pressure phase) observed in the recent experiment by Katayama et al. [Nature
      (London) 403, 170 (2000)] was successfully realized. It is found that this
      transition is caused by a breakup of the tetrahedral molecules with large volume
      contraction. The same transition is also realized by heating. This indicates that
      only the polymeric liquid can stably exist at high temperature.

PMID- 11531488
TI  - Geometry-dependent electrostatics near contact lines.
AB  - Long-ranged electrostatic interactions in electrolytes modify contact angles on
      charged substrates in a scale and geometry-dependent manner. For angles measured
      at scales smaller than the typical Debye screening length, the wetting geometry
      near the contact line must be explicitly considered. Using variational and
      asymptotic methods, we derive new transcendental equations for the contact angle
      as functions of the electrostatic potential only at the three phase contact line.
      Analytic expressions are found in certain limits and compared with predictions
      for contact angles measured with lower resolution. An estimate for electrostatic
      contributions to line tension is also given.

PMID- 11531489
TI  - Measurement of the energetics of metal film growth on a semiconductor: Ag/Si(100)
      (2 x 1).
AB  - The first direct calorimetric measurements of the energetics of metal film growth
      on a semiconductor surface are presented. The heat of adsorption of Ag on Si(100)
      (2 x 1) at 300 K decreases from approximately 347 to 246 kJ/mol with coverage in
      the first monolayer (ML) due to overlap of substrate strain from nearby Ag
      islands. It then rises quickly toward the bulk sublimation enthalpy (285 kJ/mol)
      as 3D particles grow. A wetting layer grows to 1.0 ML, but is metastable above
      approximately 0.55 ML and dewets when kinetics permit. This may be common when
      adsorbate islands induce a large strain in the substrate surface nearby.

PMID- 11531473
TI  - Measurement of the top quark p(T) distribution.
AB  - We have measured the p(T) distribution of top quarks that are pair produced in pp
      collisions at sqrt[s] = 1.8 TeV using a sample of tt decays in which we observe a
      single high- p(T) charged lepton, a neutrino, and four or more jets. We use a
      likelihood technique that corrects for the experimental bias introduced due to
      event reconstruction and detector resolution effects. The observed distribution
      is consistent with the standard model prediction. We use these data to place
      limits on the production of high- p(T) top quarks suggested in some models of
      anomalous top quark pair production.

PMID- 11531490
TI  - Self-assembly of one-dimensional surface structures: long-range interactions in
      the growth of Ir and Pd on W(110).
AB  - Self-assembly of one-dimensional surface structures is examined by tracking
      single Ir and Pd atoms on W(110) as they incorporate into chains of Ir and Pd,
      respectively. Ir adatoms move parallel to the chains, but do not come close to
      the chain sides; incorporation occurs only at the ends. Pd adatoms also migrate
      parallel to Pd chains, and incorporate at the ends. Occasionally, in the end
      region, they do jump to the side of a chain, and migrate there until they find an
      end site. Incorporation behavior for both Ir and Pd is driven by highly
      anisotropic, long-ranged interactions between atoms on the surface.

PMID- 11531491
TI  - Continuum model for low temperature relaxation of crystal steps.
AB  - High and low temperature relaxation of crystal steps are described in a unified
      picture, using a continuum model based on a modified expression of the step-free
      energy. Results are in agreement with experiments and Monte Carlo simulations of
      step fluctuations and monolayer cluster diffusion and relaxation. In an extended
      model where mass exchange with neighboring terraces is allowed, step transparency
      and a low temperature regime for unstable step meandering are found.

PMID- 11531492
TI  - Dynamic observation of an atom-sized gold wire by phase electron microscopy.
AB  - A single-atom-sized gold wire was successfully observed in real time by a newly
      developed defocus-image modulation processing electron microscope. Because of
      phase retrieval processing with spherical aberration correction, the single-atom
      strand wire was observed with high contrast and without contrast blurring. By
      carefully looking at the atomic distance, the contrast, and the dynamic behavior
      of the wire, we recognized that there are two stages of the wire. In the first
      stage the wire maintained the atomic distance in the bulk crystal, but in the
      second stage the wire showed the atomic distance of the nearest-neighbor atoms
      with weaker contrast. The gold wire was rather stable for a few seconds under
      strong electron beam illumination.

PMID- 11531493
TI  - Temperature dependence of the Kondo resonance and its satellites in CeCu2Si2.
AB  - We present high-resolution photoemission spectroscopy studies on the Kondo
      resonance of the strongly correlated Ce system CeCu2Si2. By exploiting the
      thermal broadening of the Fermi edge we analyze position, spectral weight, and
      temperature dependence of the low-energy 4f spectral features, whose major weight
      lies above the Fermi level E(F). We also present theoretical predictions based on
      the single-impurity Anderson model using an extended noncrossing approximation,
      including all spin-orbit and crystal field splittings of the 4f states. The
      excellent agreement between theory and experiment provides strong evidence that
      the spectral properties of CeCu2Si2 can be described by single-impurity Kondo
      physics down to T approximately 5 K.

PMID- 11531494
TI  - Quantum interference and ballistic transmission in nanotube electron waveguides.
AB  - The electron transport properties of well-contacted individual single-walled
      carbon nanotubes are investigated in the ballistic regime. Phase coherent
      transport and electron interference manifest as conductance fluctuations as a
      function of Fermi energy. Resonance with standing waves in finite-length tubes
      and localized states due to imperfections are observed for various Fermi
      energies. Two units of quantum conductance 2G(0) = 4e(2)/h are measured for the
      first time, corresponding to the maximum conductance limit for ballistic
      transport in two channels of a nanotube.

PMID- 11531495
TI  - Characterization of individual threading dislocations in GaN using ballistic
      electron emission microscopy.
AB  - Threading dislocations (TDs) of molecular beam epitaxy grown GaN film were
      studied with ultrahigh vacuum ballistic electron emission microscopy in order to
      quantify any fixed negative charge at identifiable TDs, with approximately 3 nm
      spatial and approximately 10 meV local barrier resolution. In contrast to several
      prior studies, we find no indication of fixed negative dislocation charge at
      specific TD structures, with a conservative upper limit of approximately 0.25 e(
      ) per c-axis unit cell. We do observe evidence of positive surface charge at TDs
      and at GaN step edges, which may be due to local piezoelectric fields.

PMID- 11531496
TI  - Oscillating sign of drag in high Landau levels.
AB  - Motivated by experiments, we study the sign of the Coulomb drag voltage in a
      double layer system in a strong magnetic field. We show that the commonly used
      Fermi golden rule approach implicitly assumes a linear dependence of intralayer
      conductivity on density, and is thus inadequate in strong magnetic fields. Going
      beyond this approach, we show that the drag voltage commonly changes sign with
      density difference between the layers. We find that, in the quantum Hall regime,
      the Hall and longitudinal drag resistivities may be comparable. Our results are
      also relevant for pumping and acoustoelectric experiments.

PMID- 11531497
TI  - Direct observation of spontaneous weak ferromagnetism in the superconductor
      ErNi2B2C.
AB  - Neutron measurements show that superconducting ErNi2B2C (T(C) = 11 K) develops
      antiferromagnetic spin density wave magnetic order (T(N) = 6 K), which squares up
      with decreasing temperature yielding a series of higher-order magnetic Bragg
      peaks with odd harmonics. Below T(WFM) = 2.3 K where magnetization indicates a
      net moment develops, even-order Bragg peaks develop which low field
      (approximately 3 Oe) polarized beam measurements show are magnetic in origin. The
      data directly demonstrate the existence of a net magnetization with a periodicity
      of 20a, confirming the microscopic coexistence of spontaneous weak ferromagnetism
      with superconductivity.

PMID- 11531499
TI  - Origin of biquadratic coupling in Fe/Cr(100) superlattices.
AB  - We investigate the magnetic properties of a (100) oriented [Fe(1.7 nm)/Cr(8.4
      nm)](10) superlattice by means of perturbed angular correlation spectroscopy. The
      magnetic ordering in the Cr layers is obtained by measuring the magnetic
      hyperfine interaction at implanted 111Cd nuclear probes. We identify dynamic
      antiferromagnetic spin fluctuations in the Cr layers and show that it gives rise
      to the biquadratic interlayer coupling.

PMID- 11531498
TI  - Terahertz responses of intrinsic Josephson junctions in high T(c)
      superconductors.
AB  - High frequency responses of intrinsic Josephson junctions up to 2.5 THz,
      including the observation of Shapiro steps under various conditions, are reported
      and discussed in this Letter. The sample was an array of intrinsic Josephson
      junctions singled out from inside a high T(C) superconducting Bi2Sr2CaCu2O(8+x)
      single crystal, with a bow-tie antenna integrated to it. The number of junctions
      in the array was controllable, the junctions were homogeneous, the distribution
      of applied irradiation among the junctions was even, and the junctions could
      synchronously respond to high frequency irradiation.

PMID- 11531500
TI  - Giant room-temperature magnetoresistance in polycrystalline Zn(0.41)Fe(2.59)O4
      with alpha-Fe2O3 grain boundaries.
AB  - A tunneling-type magnetoresistance (MR) as large as 158% is observed at T = 300 K
      in a polycrystalline Zn0.41Fe2.59O4 sample, in which the Zn0.41Fe2.59O4 grains
      are separated by insulating alpha-Fe2O3 boundaries. The huge room-temperature MR
      is attributed to the high spin polarization of Zn(0.41)Fe(2.59)O4 grains and
      antiferromagnetic correlations between magnetic domains on both sides of the
      insulating alpha-Fe2O3 boundary. The MR exhibits strong temperature dependence
      below 100 K and its magnitude is enhanced to reach 1280% at 4.2 K, which may
      arise from the Coulomb blockade effect.

PMID- 11531501
TI  - Effects of disorder on ferromagnetism in diluted magnetic semiconductors.
AB  - We present results of a numerical mean-field treatment of interacting spins and
      carriers in doped diluted magnetic semiconductors, which takes into account the
      positional disorder present in these alloy systems. Within our mean-field
      approximation, disorder enhances the ferromagnetic transition temperature for
      metallic densities not too far from the metal-insulator transition. Concurrently,
      the ferromagnetic phase is found to have very unusual temperature dependence of
      the magnetization as well as specific heat as a result of disorder. Unusual spin
      and charge transport is implied.

PMID- 11531502
TI  - Electron confinement in surface states on a stepped gold surface revealed by
      angle-resolved photoemission.
AB  - STM images show that vicinal Au(788) surfaces are made up of a uniform array of
      (111)-oriented terraces of similar width ( approximately 3.8 nm). This uniformity
      makes it possible to study the electronic structure of the resulting step
      superlattice by angle-resolved photoemission. We show that for this terrace array
      the surface state appears to be broken up into one-dimensional quantum-well
      levels, indicating total electron confinement within the terraces. The angular
      resolution allows the probability density of the terrace quantum well state to be
      mapped in reciprocal space, complementing nicely the wave function measured in
      real space by STM.

PMID- 11531503
TI  - Ferromagnetic and antiferromagnetic fluctuations of pi-d itinerant electrons
      disclosed by band-selective NMR.
AB  - We present a band-selective NMR method to probe the constituent electronic bands
      separately in the condensed molecular matter. This method is applied to an
      organic-inorganic pi-d hybrid metal, and its utility to give the static and
      dynamic spin susceptibilities for the constituent bands is demonstrated. The
      analysis of the results uncovers an exotic feature; the antiferromagnetic and
      ferromagnetic correlations are enhanced in separate bands in a single material.
      This finding provides a novel scope connecting the metal-insulator transitions in
      this system and the manganese oxides.

PMID- 11531504
TI  - Random walks of cytoskeletal motors in open and closed compartments.
AB  - Random walks of molecular motors, which bind to and unbind from cytoskeletal
      filaments, are studied theoretically. The bound and unbound motors undergo
      directed and nondirected motion, respectively. Motors in open compartments
      exhibit anomalous drift velocities. Motors in closed compartments generate
      stationary nonequilibrium states with spatially varying densities of the motor
      concentrations and currents. "Traffic jams" on the filaments lead to a maximum of
      the motor current at an optimal motor concentration. Quantitative estimates based
      on experimental data for bound motors indicate that these transport phenomena are
      accessible to experiments.

PMID- 11531505
TI  - Excitable media in a chaotic flow.
AB  - The response to a localized perturbation of an excitable medium under stirring by
      chaotic advection is investigated. It is found that below a critical stirring
      rate a localized perturbation produces a coherent global excitation of the
      system. For very slow stirring, however, the coherence of the global excitation
      is gradually lost. We propose a simple model to describe the effect of the flow
      on the excitable dynamics, and explain the observed behavior as a consequence of
      a steady excited filament state found in the reduced problem.

PMID- 11531506
TI  - Action-derived molecular dynamics in the study of rare events.
AB  - We present a practical method to generate classical trajectories with fixed
      initial and final boundary conditions. Our method is based on the minimization of
      a suitably defined discretized action. The method finds its most natural
      application in the study of rare events. Its capabilities are illustrated by
      nontrivial examples. The algorithm lends itself to straightforward
      parallelization, and when combined with ab initio molecular dynamics it promises
      to offer a powerful tool for the study of chemical reactions.

PMID- 11531507
TI  - Comment on "Observation of attosecond light localization in higher order harmonic
      generation".

PMID- 11531509
TI  - Aging in 1D discrete spin models and equivalent systems.
AB  - We derive exact expressions for a number of aging functions that are scaling
      limits of nonequilibrium correlations, R(t(w),t(w)+t) as t(w)-->infinity, t/t(w)-
      >theta, in the 1D homogenous q-state Potts model for all q with T = 0 dynamics
      following a quench from T = infinity. One such quantity is <sigma-
      >(0)(t(w));sigma-->(n)(t(w)+t)> when n/square root of ([t(w))-->z. Exact, closed
      form expressions are also obtained when an interlude of T = infinity dynamics
      occurs. Our derivations express the scaling limit via coalescing Brownian paths
      and a "Brownian space-time spanning tree," which also yields other aging
      functions, such as the persistence probability of no spin flip at 0 between t(w)
      and t(w)+t.

PMID- 11531510
TI  - A new determination of G using two methods.
AB  - We present the results of a measurement of G made with a torsion-strip balance
      used in two substantially independent ways. The two results agree to within their
      respective uncertainties; the correlation coefficient of the two methods is 
      0.18. The result is G = 6.675 59(27)x10(-11) m(3) kg(-1) s(-2) with a standard
      uncertainty of 4.1 parts in 10(5). Our result is 2 parts in 10(4) higher than the
      recent result of Gundlach and Merkowitz.

PMID- 11531514
TI  - Test of CPT and Lorentz invariance from muonium spectroscopy.
AB  - Following a suggestion from Kostelecky et al., we evaluated a test of CPT and
      Lorentz invariance from the microwave spectroscopy of muonium. Hamiltonian terms
      beyond the standard model violating CPT and Lorentz invariance would contribute
      frequency shifts deltanu(12) and deltanu(34) to nu(12) and nu(34), the two
      transitions involving muon spin flip, which were precisely measured in ground
      state muonium in a strong magnetic field of 1.7 T. The shifts would be indicated
      by anticorrelated oscillations in nu(12) and nu(34) at the Earth's sidereal
      frequency. No time dependence was found in nu(12) or nu(34) at the level of 20
      Hz, limiting the size of some CPT and Lorentz-violating parameters at the level
      of 2x10(-23) GeV.

PMID- 11531513
TI  - Neutrino-lepton masses, Zee scalars, and muon g-2.
AB  - Evidence for neutrino oscillations points to the existence of tiny but finite
      neutrino masses. Such masses may be naturally generated via radiative corrections
      in models, such as the Zee model, where a singlet Zee scalar plays a key role. We
      minimally extend the Zee model by including a right-handed singlet neutrino
      nu(R). The radiative Zee mechanism can be protected by a simple U(1)(X) symmetry
      involving only the nu(R) and a Zee scalar. We further construct a class of models
      with a single horizontal U(1)(FN) (a la Froggatt-Nielsen) such that the mass
      patterns of the neutrinos and leptons are naturally explained. We then analyze
      the muon anomalous magnetic moment (g(mu)-2) and the flavor changing mu-->egamma
      decay. The nu(R) interaction in our minimal extension is found to induce the BNL
      g(mu)-2 anomaly, with a light charged Zee scalar of mass 100-300 GeV.

PMID- 11531512
TI  - Branching ratio measurement of the decay K(L) --> e(+)e(-)mu(+)mu(-).
AB  - We have collected a 43 event sample of the decay K(L)-->e(+)e(-)mu(+)mu(-) with
      negligible backgrounds and measured its branching ratio to be (2.62+/-0.40+/
      0.17)x10(-9). We see no evidence for CP violation in this decay. In addition, we
      set the 90% confidence upper limit on the combined branching ratios for the
      lepton flavor violating decays K(L)-->e(+/-)e(+/-)mu(-/+)mu(-/+) at B(K(L)-->e(+/
      )e(+/-)mu(-/+)mu(-/+))< or =1.23x10(-10), assuming a uniform phase space
      distribution.

PMID- 11531516
TI  - Scanning the quark-gluon plasma with charmonium.
AB  - We suggest the variation of charmonium production rate with Feynman x(F) in heavy
      ion collisions as a novel and sensitive probe for the properties of the created
      matter. Final state interactions with the comoving matter create a minimum at
      x(F) = 0, which is especially deep and narrow if a quark-gluon plasma is formed.
      While a strong effect is predicted at SPS, at the RHIC energy it overlaps with
      the expected peak formed by shadowing effects and needs comparison with pA data.
      We predict a steep dependence on centrality and suggest that this new probe is
      complementary to the dependence on transverse energy, and is more sensitive to a
      scenario of final state interactions.

PMID- 11531511
TI  - Observation of Cabibbo suppressed B --> D(*)K- decays at Belle.
AB  - We report observations of the Cabibbo suppressed decays B-->D((*))K- using a 10.4
      fb(-1) data sample accumulated at the Upsilon(4S) resonance with the Belle
      detector at the KEKB e(+)e(-) storage ring. We find that the ratios of Cabibbo
      suppressed to Cabibbo favored branching fractions are B(B--->D0K-)/B(B--->D0pi(
      )) = 0.079+/-0.009+/-0.006, B(B(0)-->D+K-)/B(B(0)-->D+pi(-)) = 0.068+/-0.015+/
      0.007, B(B--->D(*0)K-)/B(B--->D(*0)pi(-)) = 0.078+/-0.019+/-0.009, and B(B(0)-
      >D(*+)K-)/B(B(0)-->D(*+)pi(-)) = 0.074+/-0.015+/-0.006. These are the first
      observations of the B-->D+K-, D(*0)K-, and D(*+)K- decay processes.

PMID- 11531515
TI  - Two-kaon correlations in central Pb+Pb collisions at 158 a GeV/c.
AB  - Two-particle interferometry of positive kaons is studied in Pb+Pb collisions at
      mean transverse momenta <p(T)> approximately 0.25 and 0.91 GeV/c. A three
      dimensional analysis was applied to the lower p(T) data, while a two-dimensional
      analysis was used for the higher p(T) data. We find that the source-size
      parameters are consistent with the m(T) scaling curve observed in pion
      correlation measurements in the same collisions, and that the duration time of
      kaon emission is consistent with zero within the experimental sensitivity.

PMID- 11531520
TI  - Sum-frequency generation in chiral liquids near electronic resonance.
AB  - We demonstrate experimentally that visible-visible sum-frequency generation in
      the bulk of a chiral liquid is observable near electronic resonant transitions.
      Although the process is electric dipole allowed, it is rather weak because the
      orientational average over molecules effectively reduces the bulk chiral
      nonlinearity.

PMID- 11531519
TI  - Rapidity dependence of antiproton-to-proton ratios in Au+Au collisions at square
      root of (sNN) = 130 GeV.
AB  - Measurements, with the BRAHMS detector, of the antiproton-to-proton ratio at
      midrapidities and forward rapidities, are presented for Au+Au reactions at square
      root of [s(NN)] = 130 GeV, and for three different collision centralities. For
      collisions in the 0%-40% centrality range, we find N(&pmacr;)/N(p) = 0.64+/
      0.04((stat))+/-0.06((syst)) at y approximately 0, 0.66+/-0.03+/-0.06 at y
      approximately 0.7, and 0.41+/-0.04+/-0.06 at y approximately 2. The ratios are
      found to be nearly independent of collision centrality and transverse momentum.
      The antiproton and proton rapidity densities vary differently with rapidity, and
      indicate a significant degree of collision transparency, although a net-baryon
      free midrapidity plateau (Bjorken limit) is not yet reached.

PMID- 11531521
TI  - Quantal density functional theory of excited states.
AB  - We explain by quantal density functional theory the physics of mapping from any
      bound nondegenerate excited state of Schrodinger theory to an S system of
      noninteracting fermions with equivalent density and energy. The S system may be
      in a ground or excited state. In either case, the highest occupied eigenvalue is
      the negative of the ionization potential. We demonstrate this physics with
      examples. The theory further provides a new framework for calculations of atomic
      excited states including multiplet structure.

PMID- 11531518
TI  - Model-independent source imaging using two-pion correlations in (2 to 8)a GeV
      Au+Au collisions.
AB  - We report a particle source imaging analysis based on two-pion correlations in
      high multiplicity Au+Au collisions at beam energies between 2A and 8A GeV. We
      apply the imaging technique introduced by Brown and Danielewicz, which allows a
      model-independent extraction of source functions with useful accuracy out to
      relative pion separations of about 20 fm. The extracted source functions have
      Gaussian shapes. Values of source functions at zero separation are almost
      constant across the energy range under study. Imaging results are found to be
      consistent with conventional source parameters obtained from a multidimensional
      Hanburg-Brown-Twiss analysis.

PMID- 11531522
TI  - Superresolution of pulsed multiphoton Raman transitions.
AB  - We have investigated higher order multiphoton Raman resonances with two pulsed
      optical frequencies. Multiphoton transfer with up to 50 photons is observed with
      milliwatts of laser power. We demonstrate that the spectral width of the
      multiphoton resonances can be far below the Fourier transform linewidth of the
      driving optical pulses. The functional dependence of the transition linewidth on
      the number of exchanged photons is found to vary with the pulse shape. Our
      experiment is performed with laser-cooled rubidium atoms confined in a CO2-laser
      optical dipole trap.

PMID- 11531523
TI  - Spatial mode control of radiation generated by frequency difference in
      periodically poled crystals.
AB  - We demonstrate the possibility to control the spatial mode of a narrow-linewidth,
      continuous-wave, infrared radiation beam generated by difference frequency in a
      periodically poled crystal. This can be achieved by acting directly on a few
      experimental parameters. We show that hollow beams can be generated. A numerical
      routine has been developed and results agree with experimental observations,
      without requiring any free parameters. The relevance of these results for high
      resolution spectroscopy and atom manipulation is discussed.

PMID- 11531524
TI  - Dynamics of classical wave scattering by small obstacles.
AB  - A causality problem in the time-dependent scattering of classical waves from
      point scatterers is pointed out and analyzed. Based on an alternative model, the
      leading pole approximation of the exact scattering matrix of the square-well
      potential, transparent expressions for the time- and position-dependent Green
      function in a disordered medium are derived.

PMID- 11531525
TI  - Anomalous diffusion and dynamical localization in polygonal billiards.
AB  - We study numerically classical and quantum dynamics of a piecewise parabolic area
      preserving map on a cylinder which emerges from the bounce map of elongated
      triangular billiards. The classical map exhibits anomalous diffusion.
      Quantization of the same map results in a system with dynamical localization and
      pure point spectrum.

PMID- 11531527
TI  - Dynamic patterns and self-knotting of a driven hanging chain.
AB  - When shaken vertically, a hanging chain displays a startling variety of distinct
      behaviors. We find experimentally that instabilities occur in tonguelike bands of
      parameter space, to swinging or rotating pendular motion, or to chaotic states.
      Mathematically, the dynamics are described by a nonlinear wave equation. A linear
      stability analysis predicts instabilities within the well-known resonance
      tongues; their boundaries agree very well with experiment. Full simulations of
      the 3D dynamics reproduce and elucidate many aspects of the experiment. The chain
      is also observed to tie knots in itself, some quite complex. This is beyond the
      reach of the current analysis and simulations.

PMID- 11531526
TI  - Asymmetric kinks: stabilization by entropic forces.
AB  - Asymmetric kinks bridging two adjacent potential valleys of equal depth but
      different curvature are unstable against phonon modes. When coupled to a heat
      bath, a kink-bearing string tends to cross over into the shallower valley; kinks
      are thus predicted to drift in the appropriate direction with velocity
      proportional to the temperature, in close agreement with numerical simulation.
      When contrasted by a mechanical bias, these entropic forces give rise to a rich
      phenomenology that includes configurational phase transitions, double-kink
      dissociation, and noise-directed signal transmission.

PMID- 11531517
TI  - Multiplicity distribution and spectra of negatively charged hadrons in Au+Au
      collisions at square root of (sNN) = 130 GeV.
AB  - The minimum-bias multiplicity distribution and the transverse momentum and
      pseudorapidity distributions for central collisions have been measured for
      negative hadrons ( h(-)) in Au+Au interactions at square root of ([s(NN)]) = 130
      GeV. The multiplicity density at midrapidity for the 5% most central interactions
      is dN(h(-))/d(eta)/(eta = 0) = 280+/-1(stat)+/-20(syst), an increase per
      participant of 38% relative to pp collisions at the same energy. The mean
      transverse momentum is 0.508+/-0.012 GeV/c and is larger than in central Pb+Pb
      collisions at lower energies. The scaling of the h(-) yield per participant is a
      strong function of p( perpendicular). The pseudorapidity distribution is almost
      constant within /eta/<1.

PMID- 11531528
TI  - Optimal symplectic approximation of Hamiltonian flows.
AB  - Long term simulations of Hamiltonian dynamical systems benefit from enforcing the
      symplectic symmetry. One of the several available methods to perform this
      symplectification is provided by the recently developed theory of extended
      generating functions. The theory offers an infinite supply of generator types
      that can be used for symplectification. Using Hofer's metric, a condition for
      optimal symplectification is given. In the weakly nonlinear case, the condition
      provides a generator type that, based on the limited information available on the
      system, in general gives optimal results.

PMID- 11531529
TI  - Observation of zero current density in the core of jet discharges with lower
      hybrid heating and current drive.
AB  - Simultaneous current ramping and application of lower hybrid heating and current
      drive (LHCD) have produced a region with zero current density within measurement
      errors in the core ( r/a< or =0.2) of JET tokamak optimized shear discharges. The
      reduction of core current density is consistent with a simple physical
      explanation and numerical simulations of radial current diffusion including the
      effects of LHCD. However, the core current density is clamped at zero, indicating
      the existence of a physical mechanism which prevents it from becoming negative.

PMID- 11531530
TI  - Normal modes of 2D finite clusters in complex plasmas.
AB  - Finite clusters with a small number of charged particles immersed in a complex
      plasma environment have been investigated experimentally. Finite clusters in
      complex plasmas are shown to be a unique system for the excitation and
      observation of normal modes in bounded charged-particle systems. In systems of 3,
      4, and 7 particles, normal-mode oscillations have been excited and from the
      frequencies of the different modes the key parameters, particle charge, and the
      screening strength have been derived. This method is proposed to be applied in
      future microgravity experiments.

PMID- 11531531
TI  - Using Fermi statistics to create strongly coupled ion plasmas in atom traps.
AB  - We investigate the possibility of forming a strongly coupled ion plasma from a
      cold atomic gas. We show that rapid ion heating occurs as correlations develop
      from the initial disordered configuration. This heating severely reduces the
      Coulomb coupling of the final configuration, although the final Coulomb coupling
      can be maximized by introducing order into the initial atomic gas. We show that
      such order can be introduced into the initial state by employing a degenerate
      Fermi gas whereby the Pauli hole mimics the Coulomb hole. The corresponding
      initial state correlations can enhance the Coulomb coupling in the final state by
      orders of magnitude.

PMID- 11531532
TI  - Ion separation due to magnetic field penetration into a multispecies plasma.
AB  - The magnetic field, the electron density, and the ion velocities in a
      multispecies plasma conducting a high fast-rising current are determined using
      simultaneous spectroscopic measurements. It is found that ion separation occurs
      in which a light-ion plasma is pushed ahead while a heavy-ion plasma lags behind
      the magnetic piston. We show that most of the momentum imparted by the magnetic
      field pressure is taken by the reflected light ions, and most of the dissipated
      magnetic field energy is converted into kinetic energy of these ions, even though
      their mass is only a small part of the total plasma mass. Such species separation
      with implications to the momenta and energy partitioning is shown to be of a
      general nature.

PMID- 11531533
TI  - Time scaling regimes in aggregation of magnetic dipolar particles: scattering
      dichroism results.
AB  - We report experimental results on the aggregation kinetics in magnetorheological
      fluids subject to a constant uniaxial magnetic field using the technique of
      scattering dichroism. We show that the number of aggregated particles displays a
      long-time power-law dependence with exponents that correspond to two different
      aggregation regimes. These regimes coincide with 3D and 1D-like aggregation. We
      also derive the values of both time exponents for the number of aggregated
      particles.

PMID- 11531534
TI  - Effect of phonon scattering by surface roughness on the universal thermal
      conductance.
AB  - The effect of phonon scattering by surface roughness on the thermal conductance
      in mesoscopic systems at low temperatures is calculated using full elasticity
      theory. The low frequency behavior of the scattering shows novel power law
      dependences arising from the unusual properties of the elastic modes. This leads
      to new predictions for the low temperature depression of the thermal conductance
      below the ideal universal value. Comparison with the data of Schwab et al.
      [Nature (London) 404, 974 (2000)] suggests that surface roughness on a scale of
      the width of the thermal pathway is important in the experiment.

PMID- 11531535
TI  - Vacancy dynamics and reorganization on bromine-etched Si(100)-(2 x 1) surfaces.
AB  - Halogen etching of Si(100) surfaces has long been considered to involve the
      selective removal of atoms from an essentially static surface. Here we show that
      vacancy sites produced by etching are mobile at elevated temperature and
      rearrange to form features that were considered to be the direct products of
      etching. We demonstrate that the etch features observed at different temperatures
      are not due to different mechanisms. Rather, kinetic etch products formed at low
      temperatures are transformed into thermodynamically more stable features at
      higher temperatures.

PMID- 11531536
TI  - Phase-field formulation for quantitative modeling of alloy solidification.
AB  - A phase-field formulation is introduced to simulate quantitatively
      microstructural pattern formation in alloys. The thin-interface limit of this
      formulation yields a much less stringent restriction on the choice of interface
      thickness than previous formulations and permits one to eliminate nonequilibrium
      effects at the interface. Dendrite growth simulations with vanishing solid
      diffusivity show that both the interface evolution and the solute profile in the
      solid are accurately modeled by this approach.

PMID- 11531537
TI  - Elastoplastic contact between randomly rough surfaces.
AB  - I have developed a theory of contact mechanics between randomly rough surfaces.
      The solids are assumed to deform elastically when the stress sigma is below the
      yield stress sigma(Y), and plastically when sigma reaches sigma(Y). I study the
      dependence of the (apparent) area of contact on the magnification. I show that in
      most cases the area of real contact A is proportional to the load. If the rough
      surface is self-affine fractal (Hurst exponent H) the whole way up to the lateral
      size L of the nominal contact area, then (assuming no plastic deformation) A
      approximately L(H).

PMID- 11531538
TI  - Thermally activated stripe reconstruction induced by O on Nb (011).
AB  - We report scanning tunneling microscopy and low energy electron microscopy (LEEM)
      observations for thin films of Nb (011) of stripe-phase behavior by two variants
      of an O-induced reconstruction. Stripes occur for thin films but not bulk
      crystals. At low temperatures the less-favored variant is thermally activated as
      single stripes on surface heterogeneities. Near T0 = 1505 K, where the
      reconstruction is lifted, the stripes crowd to form a periodic array with a
      temperature dependent spacing. LEEM permits quantitative insight into stripe
      behavior and reveals novel details of stripes interacting with topographic
      features such as steps, facets, and dislocations.

PMID- 11531539
TI  - Shot noise for resonant Cooper pair tunneling.
AB  - We study intrinsic noise of current in a superconducting single-electron
      transistor, taking into account both coherence effects and Coulomb interaction
      near a Cooper pair resonance. Because of this interplay, the statistics of
      tunneling events deviates from the Poisson distribution and, more important, it
      shows even-odd asymmetry in the transmitted charge. The zero-frequency noise is
      suppressed significantly when the quasiparticle tunneling rates are comparable to
      the coherent oscillation frequency of Cooper pairs.

PMID- 11531540
TI  - Measurements of the complex conductivity of NbxSi(1-x) alloys on the insulating
      side of the metal-insulator transition.
AB  - We have conducted temperature and frequency dependent transport measurements in
      amorphous NbxSi1-x samples in the insulating regime. We find a temperature
      dependent dc conductivity consistent with variable range hopping in a Coulomb
      glass. The frequency dependent response in the millimeter-wave frequency range
      can be described by the expression sigma(omega) varies with (-iota omega)(alpha)
      with the exponent somewhat smaller than 1. Our ac results are not consistent with
      extant theories for the hopping transport.

PMID- 11531541
TI  - Universal conductance distributions in the crossover between diffusive and
      localization regimes.
AB  - The full distribution of the conductance P(G) in quasi-one-dimensional wires with
      rough surfaces is analyzed from the diffusive to the localization regime. In the
      crossover region, where the statistics is dominated by only one or two
      eigenchannels, the numerically obtained P(G) is found to be independent of the
      details of the system with the average conductance <G> as the only scaling
      parameter. For <G><e(2)/h, P(G) is given by an essentially "one-sided" log-normal
      distribution. In contrast, for e(2)/h< <G> < or =2e(2)/h, the shape of P(G)
      remarkably agrees with those predicted by random matrix theory for two
      fluctuating transmission eigenchannels.

PMID- 11531542
TI  - Orbital ferromagnetism and anomalous Hall effect in antiferromagnets on the
      distorted fcc lattice.
AB  - The Berry phase due to the spin wave function gives rise to the orbital
      ferromagnetism and anomalous Hall effect in the noncoplanar antiferromagnetic
      ordered state on face-centered-cubic (fcc) lattice once the crystal is distorted
      perpendicular to the (1,1,1) or (1,1,0) plane. The relevance to the real systems
      gamma-FeMn and NiS2 is also discussed.

PMID- 11531543
TI  - Tunable adsorption on carbon nanotubes.
AB  - We investigated the adsorption of a single atom, hydrogen and aluminum, on single
      wall carbon nanotubes from first principles. The adsorption is exothermic, and
      the associated binding energy varies inversely as the radius of the zigzag tube.
      We found that the adsorption of a single atom and related properties can be
      modified continuously and reversibly by the external radial deformation. The
      binding energy on the high curvature site of the deformed tube increases with
      increasing radial deformation. The effects of curvature and radial deformation
      depend on the chirality of the tube.

PMID- 11531544
TI  - Thermal activation between Landau levels in the organic superconductor beta(")
      (BEDT-TTF)2SF5CH2CF2SO3.
AB  - We show that Shubnikov-de Haas oscillations in the interlayer resistivity of the
      organic superconductor beta(")-(BEDT-TTF)2SF5CH2CF2SO3 become very pronounced in
      magnetic fields approximately 60 T. The conductivity minima exhibit thermally
      activated behavior that can be explained simply by the presence of a Landau gap,
      with the quasi-one-dimensional Fermi surface sheets contributing negligibly to
      the conductivity. This observation, together with complete suppression of
      chemical potential oscillations, is consistent with an incommensurate nesting
      instability of the quasi-one-dimensional sheets.

PMID- 11531545
TI  - Doubling of the bands in overdoped Bi2Sr2CaCu2O(8+delta): evidence for c-axis
      bilayer coupling.
AB  - We present high resolution angle resolved photoemission data of the bilayer
      superconductor Bi(2)Sr(2)CaCu(2)O(8+delta) (Bi2212) showing a clear doubling of
      the near E(F) bands. This splitting approaches zero along the (0,0)-->(pi,pi)
      nodal line and is not observed in single layer Bi(2)Sr(2)CuO(6+delta) (Bi2201),
      indicating that the splitting is due to the long sought after bilayer splitting
      effect. The splitting has a magnitude of approximately 75 meV near the middle of
      the zone, extrapolating to about 110 meV near the (pi,0) point. The existence of
      these two bands also helps to clear up the recent controversy concerning the
      topology of the Fermi surface.

PMID- 11531546
TI  - Bethe ansatz results for the 4f-electron spectra of a degenerate Anderson model.
AB  - We show that the density of states for localized 4f electrons coupled to a
      conduction band calculated in the framework of Bethe ansatz solution for the
      degenerate Anderson model qualitatively disagree with the well-known results
      obtained for the same model but using a variational approach. The scales of
      parameters used in our Bethe ansatz calculations to fit the experiments disagree
      with the commonly accepted values from other studies. This implies narrower
      conduction bands hybridized with 4f orbitals or questions the applicability of
      the Bethe ansatz for a degenerate Anderson model for the high-energy
      characteristics of some rare-earth systems.

PMID- 11531547
TI  - Quantum communication between N partners and Bell's inequalities.
AB  - We consider a family of quantum communication protocols involving N partners. We
      demonstrate the existence of a link between the security of these protocols
      against individual attacks by the eavesdropper, and the violation of some Bell's
      inequalities, generalizing the link that was noticed some years ago for two
      partners quantum cryptography. The arguments are independent of the local hidden
      variable debate.

PMID- 11531548
TI  - Clock synchronization with dispersion cancellation.
AB  - The dispersion cancellation feature of pulses which are entangled in frequency is
      employed to synchronize clocks of distant parties. The proposed protocol is
      insensitive to the pulse distortion caused by transit through a dispersive
      medium. Since there is cancellation to all orders, also the effects of slowly
      fluctuating dispersive media are compensated. The experimental setup can be
      realized with currently available technology, at least for a proof of principle.

PMID- 11531549
TI  - Subdiffusion-limited A+A reactions.
AB  - We consider the coagulation dynamics A+A-->A and A+A <==> A and the annihilation
      dynamics A+A-->0 for particles moving subdiffusively in one dimension. This
      scenario combines the "anomalous kinetics" and "anomalous diffusion" problems,
      each of which leads to interesting dynamics separately and to even more
      interesting dynamics in combination. Our analysis is based on the fractional
      diffusion equation.

PMID- 11531550
TI  - Theoretical description of teaching-learning processes: a multidisciplinary
      approach.
AB  - A multidisciplinary approach based on concepts from sociology, educational
      psychology, statistical physics, and computational science is developed for the
      theoretical description of teaching-learning processes that take place in the
      classroom. The emerging model is consistent with well-established empirical
      results, such as the higher achievements reached working in collaborative groups
      and the influence of the structure of the group on the achievements of the
      individuals. Furthermore, another social learning process that takes place in
      massive interactions among individuals via the Internet is also investigated.

PMID- 11531551
TI  - Comment on "period doubling of a torus near the ferroelectric phase transition of
      a KH2PO4 crystal".

PMID- 11531553
TI  - Comment on "noncausal time response in frustrated total internal reflection?".

PMID- 11531556
TI  - Comment on "extremely low frequency plasmons in metallic mesostructures".

PMID- 11531555
TI  - Comment on "effect of potential energy distribution on the melting of clusters".

PMID- 11531557
TI  - Proposed source of gravitational radiation from a torus around a black hole.
AB  - Long gamma-ray bursts (GRBs) could be emitted from rapidly spinning black-hole
      torus systems, resulting from either hypernovae or black-hole-neutron-star
      coalescence. We show that a nonaxisymmetric torus may also radiate gravitational
      radiation, powered by the spin energy of the black hole. The coupling to the spin
      energy of the black hole operates by equivalence in poloidal topology to pulsar
      magnetospheres. Results calculated in the suspended-accretion state indicate that
      GRBs are potentially the most powerful LIGO/VIRGO burst sources in the Universe,
      with an expected duration of 10-15 s on a horizontal branch of 1-2 kHz in the
      f(f) diagram.

PMID- 11531558
TI  - Further evidence for cosmological evolution of the fine structure constant.
AB  - We describe the results of a search for time variability of the fine structure
      constant alpha using absorption systems in the spectra of distant quasars. Three
      large optical data sets and two 21 cm and mm absorption systems provide four
      independent samples, spanning approximately 23% to 87% of the age of the
      universe. Each sample yields a smaller alpha in the past and the optical sample
      shows a 4 sigma deviation: Delta alpha/alpha = -0.72+/-0.18 x 10(-5) over the
      redshift range 0.5<z<3.5. We find no systematic effects which can explain our
      results. The only potentially significant systematic effects push Delta
      alpha/alpha towards positive values; i.e., our results would become more
      significant were we to correct for them.

PMID- 11531559
TI  - Lorentz invariance and origin of symmetries.
AB  - We reconsider the role of Lorentz invariance in the dynamical generation of the
      observed internal symmetries. We argue that, generally, Lorentz invariance can be
      imposed only in the sense that all Lorentz noninvariant effects caused by the
      spontaneous breakdown of Lorentz symmetry are physically unobservable. The
      application of this principle to the most general relativistically invariant
      Lagrangian, with arbitrary couplings for all the fields involved, leads to the
      appearance of a symmetry and, what is more, to the massless vector fields gauging
      this symmetry in both Abelian and non-Abelian cases. In contrast, purely global
      symmetries are generated only as accidental consequences of the gauge symmetry.

PMID- 11531563
TI  - Kohn-Sham theory for ground-state ensembles.
AB  - An electron density distribution n(r) which can be represented by that of a
      single-determinant ground state of noninteracting electrons in an external
      potential v(r) is called pure-state v-representable (P-VR). Most physical
      electronic systems are P-VR. Systems which require a weighted sum of several such
      determinants to represent their density are called ensemble v-representable (E
      VR). This paper develops formal Kohn-Sham equations for E-VR physical systems,
      using the appropriate coupling constant integration. It also derives local
      density- and generalized gradient approximations, and conditions and corrections
      specific to ensembles.

PMID- 11531562
TI  - Superheavy hydrogen (5)H.
AB  - Experimental search for (5)H using a secondary beam of (6)He has been performed.
      The transfer reaction (1)H((6)He,(2)He)(5)H was studied by detecting two protons
      emitted from the decay of (2)He. A peak consistent with a (5)H resonance at 1.7+/
      0.3 MeV above the n+n+t threshold was observed, with a width of 1.9+/-0.4 MeV.
      The angular distribution of the (1)H((6)He,(2)He)(5)H reaction was measured as
      well as the energy correlation of the two protons.

PMID- 11531564
TI  - Theory of molecule-surface scattering at thermal and hyperthermal energies.
AB  - A theoretical model of molecule-surface scattering is developed which includes
      energy and momentum transfers between the surface and projectile for both
      translational and rotational motions and internal mode excitation for the
      projectile molecule. The translation and rotation motions are treated in the
      classical limit, while a quantum treatment for internal vibrational mode
      excitation is used. The results of calculations are compared with recent high
      precision measurements of the scattering of a beam of C(2)H(2) molecules from a
      clean, ordered LiF(001) surface at energies of up to nearly 1 eV. The calculated
      results for angular distributions and rotational excitations are in good
      agreement with experiment.

PMID- 11531565
TI  - Sub-ppm laser spectroscopy of antiprotonic helium and a CPT-violation limit on
      the antiprotonic charge and mass.
AB  - Six laser-resonant transitions have been detected in metastable antiprotonic
      helium atoms produced at the CERN Antiproton Decelerator. They include UV
      transitions from the last metastable states in the v = n-l-1 = 0 and 1 cascades.
      Zero-density frequencies were obtained from measured pressure shifts with
      fractional precisions between 1.3 x 10(-7) and 1.6 x 10(-6). By comparing these
      with QED calculations and the antiproton cyclotron frequency, we deduce that the
      antiproton and proton charges and masses agree to within 6 x 10(-8) with a
      confidence level of 90%.

PMID- 11531566
TI  - Conditional large Fock state preparation and field state reconstruction in cavity
      QED.
AB  - We propose a scheme for producing large Fock states in cavity QED via the
      implementation of a highly selective atom-field interaction. It is based on Raman
      excitation of a three-level atom by a classical field and a quantized field mode.
      Selectivity appears when one tunes to resonance a specific transition inside a
      chosen atom-field subspace, while other transitions remain dispersive, as a
      consequence of the field dependent electronic energy shifts. We show that this
      scheme can be also employed for reconstructing, in a new and efficient way, the
      Wigner function of the cavity field state.

PMID- 11531567
TI  - Distribution of proper delay times in quantum chaotic scattering: a crossover
      from ideal to weak coupling.
AB  - The probability distribution of the proper delay times during scattering on a
      chaotic system is derived in the framework of the random matrix approach and the
      supersymmetry method. The result obtained is valid for an arbitrary number of
      scattering channels as well as arbitrary coupling to the energy continuum. The
      case of statistically equivalent channels is studied in detail. In particular,
      the semiclassical limit of an infinite number of weak channels is paid
      appreciable attention.

PMID- 11531568
TI  - Onset of coherent oscillations in turbulent Rayleigh-Benard convection.
AB  - We report temperature cross correlation and velocity profile measurements in the
      aspect-ratio-one convection cell filled with water. A sharp transition from a
      random chaotic state to a correlated turbulent state of finite coherence time is
      found when the Rayleigh number becomes larger than a critical value Ra(c)
      approximately equal to 5 x 10(7). The experiment reveals a unique mechanism for
      the onset of coherent oscillations in turbulent Rayleigh-Benard convection.

PMID- 11531569
TI  - High-gradient millimeter-wave accelerator on a planar dielectric substrate.
AB  - We report the first high-gradient studies of a millimeter-wave accelerator,
      employing for the first time a planar dielectric accelerator, powered by means of
      a 0.5-A, 300-MeV, 11.424-GHz drive electron beam, synchronous at the 8th
      harmonic, 91.392 GHz. Embedded in a ring-resonator circuit within the electron
      beam line vacuum, this structure was operated at 20 MeV/m, with a circulating
      power of 200 kW, for 2 x 10(5) pulses, with no sign of breakdown, dielectric
      charging, or other deleterious high-gradient phenomena. We also present the first
      measurement of the quadrupolar content of an accelerating mode.

PMID- 11531571
TI  - Rapid large-scale magnetic-field dissipation in a collisionless current sheet via
      coupling between Kelvin-Helmholtz and lower-hybrid drift instabilities.
AB  - Rapid large-scale magnetic-field dissipation is observed in a full kinetic
      simulation of cross-field current instabilities in a current sheet even when the
      thickness of the current sheet is at ion scale. The Kelvin-Helmholtz instability
      caused by the velocity shear between the current-carrying ions and the cold
      background ions excites the lower-hybrid drift instability at the edges of the
      undulated current sheet. We show that the nonlinear coupling between these two
      instabilities is responsible for the observed rapid dissipation. The simulation
      result presents a new route for magnetic-field dissipation in an ion-scale
      current sheet and demonstrates the general significance of nonlinear cross-scale
      coupling in collisionless plasmas.

PMID- 11531570
TI  - High-efficiency beam extraction and collimation using channeling in very short
      bent crystals.
AB  - A silicon crystal was used to channel and extract 70 GeV protons from the U-70
      accelerator with an efficiency of 85.3+/-2.8%, as measured for a beam of
      approximately 10(12) protons directed towards crystals of approximately 2 mm
      length in spills of approximately 2 s duration. The experimental data follow very
      well the prediction of Monte Carlo simulations. This demonstration is important
      in devising a more efficient use of the U-70 accelerator in Protvino and provides
      crucial support for implementing crystal-assisted slow extraction and collimation
      in other machines, such as the Tevatron, RHIC, the AGS, the SNS, COSY, and the
      LHC.

PMID- 11531572
TI  - Hydrogen-enhanced local plasticity in aluminum: an ab initio study.
AB  - Dislocation core properties of Al with and without H impurities are studied using
      the Peierls-Nabarro model with parameters determined by ab initio calculations.
      We find that H not only facilitates dislocation emission from the crack tip but
      also enhances dislocation mobility dramatically, leading to macroscopically
      softening and thinning of the material ahead of the crack tip. We observe strong
      binding between H and dislocation cores, with the binding energy depending on
      dislocation character. This dependence can directly affect the mechanical
      properties of Al by inhibiting dislocation cross-slip and developing slip
      planarity.

PMID- 11531561
TI  - Observation of large CP violation in the neutral B meson system.
AB  - We present a measurement of the standard model CP violation parameter sin2 phi(1)
      based on a 29.1 fb(-1) data sample collected at the Upsilon(4S) resonance with
      the Belle detector at the KEKB asymmetric-energy e(+)e(-) collider. One neutral B
      meson is fully reconstructed as a J/psi K(S), psi(2S)K(S), chi(c1)K(S),
      eta(c)K(S), J/psi K(L), or J/psi K(*0) decay and the flavor of the accompanying B
      meson is identified from its decay products. From the asymmetry in the
      distribution of the time intervals between the two B meson decay points, we
      determine sin2 phi(1) = 0.99+/-0.14(stat)+/-0.06(syst). We conclude that we have
      observed CP violation in the neutral B meson system.

PMID- 11531573
TI  - Nature of e(g) electron order in La(1-x)Sr(1+x)MnO(4).
AB  - X-ray scattering measurements of the low-temperature structure of La(1
      x)Sr(1+x)MnO(4) ( 0.33< or =x< or =0.67) indicate the existence of three distinct
      regions: a disordered phase (x<0.4), a charge-ordered phase (x> or =0.5), and a
      mixed phase (0.4< or =x<0.5). For x>0.5, the modulation vector associated with
      the charge order is incommensurate with the lattice and depends linearly on the
      concentration of e(g) electrons. The primary superlattice reflections are
      strongly suppressed along the modulation direction and the higher harmonics are
      weak, implying the existence of a largely transverse and nearly sinusoidal
      structural distortion, consistent with a charge-density wave of the e(g)
      electrons.

PMID- 11531574
TI  - Ab initio design of perovskite alloys with predetermined properties: the case of
      Pb(Sc(0.5)Nb(0.5))O(3).
AB  - A first-principles derived approach is combined with the inverse Monte Carlo
      technique to determine the atomic orderings leading to prefixed properties in
      Pb(Sc(0.5)Nb(0.5))O(3) perovskite alloy. We find that some arrangements between
      Sc and Nb atoms result in drastic changes with respect to the disordered
      material, including ground states of new symmetries, large enhancement of
      electromechanical responses, and considerable shift of the Curie temperature. We
      discuss the microscopic mechanisms responsible for these unusual effects.

PMID- 11531575
TI  - Electronic structure and field-emission characteristics of open-ended single
      walled carbon nanotubes.
AB  - The field-emission mechanism of open-ended single-walled carbon nanotubes (SWNTs)
      is studied. Owing to electronic effects that directly alter the bonding mode and
      remarkably influence the work function, an open-ended SWNT has much better field
      emission properties than a closed SWNT; owing to geometrical effects that
      slightly influence the work function and the amplification factor, an open-ended
      SWNT with relaxation has higher threshold voltage and higher current density
      compared to one without relaxation. It is suggested that adjusting the localized
      electronic states of the emitting regions, by electronic and geometrical means,
      could improve the field-emission properties of carbon nanotubes.

PMID- 11531576
TI  - Size-dependent melting of self-assembled indium nanostructures.
AB  - We have measured the melting temperature of nanoscale indium islands on a WSe(2)
      substrate using perturbed angular correlations combined with scanning tunneling
      microscopy. The indium islands are self-assembled nanostructures whose diameter
      can vary between about 5 and 100 nm, depending on deposition conditions. The
      melting point decreases due to surface energies as the islands get smaller. This
      decrease depends on the faceting of the crystalline nanostructures and
      interactions between the islands and the substrate.

PMID- 11531577
TI  - Morphological instability of liquid metallic nuclei condensing on charged
      inhomogeneities.
AB  - We analyze the heterogeneous nucleation of liquid metallic phase from vapor on an
      electrically charged inhomogeneity. It is demonstrated theoretically that,
      regardless of magnitudes of surface tension of the phase interface and electric
      charge carried by the inhomogeneity, all spherical nuclei are necessarily
      unstable at all external pressures for which the system is undersaturated. In
      other words, small perturbations to the shape of the interface will cause it to
      move away from the equilibrium configuration. Our treatment of the problem is
      based on the continuum thermodynamic approach pioneered by Gibbs and Thomson.

PMID- 11531578
TI  - Mesoscopic correlation of supramolecular chirality in one-dimensional hydrogen
      bonded assemblies.
AB  - The ordering of 4-[trans-2-(pyrid-4-yl-vinyl)] benzoic acid, a two-dimensional
      chiral species, was studied by scanning tunneling microscopy at noble metal
      surfaces. Homochiral molecules self-assemble in supramolecular chiral hydrogen
      bonded twin chains, which order in nanogratings where the supramolecular
      chirality is strictly correlated over the entire microm domains without intimate
      molecular contact. Model simulations indicate that the underlying mesoscopic
      chiral resolution is associated with twin chains acting as chiroselective
      templates for transient molecular attachment, which process mediates the
      gratings' evolution.

PMID- 11531579
TI  - Unusual Multilayer Surface Alloy: Al(100)-c(2 x 2)-2Li.
AB  - An unusual multilayer surface alloy is formed by adsorption of one monolayer Li
      on Al(100). It is shown by low energy electron diffraction that the first three
      layers consist of a mixed Al-Li layer, a pure Al layer, and a second Al-Li layer.
      Thus the alloy has the same layer stoichiometry as the (100) surface of the
      metastable Al(3)Li bulk alloy. However, the relative orientation of the two mixed
      layers is the same as that in the Al(3)Ti-type structure. These findings are
      confirmed by total-energy calculations, which lead further to the prediction that
      the bulk Al(3)Li alloy has a faulted, Al(3)Ti-type surface.

PMID- 11531580
TI  - Coexistence of atomic and molecular chemisorption states: H(2)/Pd(210).
AB  - A novel H(2) molecular adsorption state on metal surfaces has been detected by
      temperature-programmed desorption and electron energy loss spectroscopy
      experiments of the H(2)/Pd(210) system. The molecular nature of this state has
      been verified by isotope exchange experiments. This molecular state leads to a
      decrease of the surface work function while atomic hydrogen on Pd(210) causes an
      increase. Ab initio total-energy calculations have confirmed all experimental
      findings. Through these calculations the microscopic nature of this novel
      molecular adsorption state could be identified; it turns out that this state is
      stabilized by the presence of atomic hydrogen on the Pd(210) surface.

PMID- 11531581
TI  - Viscosity of interfacial water.
AB  - The effective shear viscosity and frequency-dependent dynamic oscillatory shear
      spectra of water containing monovalent or divalent ions (ionic strength 25 mM),
      confined between mica crystals at 1-2 water molecules thickness, oscillated with
      twist angle with the period expected for the pseudohexagonal surface lattice. The
      effective viscosity varied by orders of magnitude as the twist angle was changed.
      Confinement appeared to imprint lateral spatial correlation on the ultrathin
      liquid, the more so the better the confining lattices were aligned, but the oft
      proposed "ice structure" was not observed dynamically.

PMID- 11531582
TI  - Rate-dependent slip of Newtonian liquid at smooth surfaces.
AB  - Newtonian fluids were placed between molecularly smooth surfaces whose spacing
      was vibrated at spacings where the fluid responded as a continuum. Hydrodynamic
      forces agreed with predictions from the no-slip boundary condition only provided
      that flow rate (peak velocity normalized by spacing) was low, but implied partial
      slip when it exceeded a critical level, different in different systems,
      correlated with contact angle (surface wettability). With increasing flow rate
      and partially wetted surfaces, hydrodynamic forces became up to 2-4 orders of
      magnitude less than expected by assuming the no-slip boundary condition that is
      commonly stated in textbooks.

PMID- 11531583
TI  - Nanomechanical resonator shuttling single electrons at radio frequencies.
AB  - We observe transport of electrons through a metallic island on the tip of a
      nanomechanical pendulum. The resulting tunneling current shows distinct features
      corresponding to the discrete mechanical eigenfrequencies of the pendulum. We
      report on measurements covering the temperature range from 300 down to 4.2 K. We
      explain the I-V curve, which unexpectedly differs from previous theoretical
      predictions, with model calculations based on a master equation approach.

PMID- 11531584
TI  - Depinning with dynamic stress overshoots: mean field theory.
AB  - An infinite-range model of an elastic manifold pulled through a random potential
      by a force F is analyzed focusing on inertial effects. When the inertial
      parameter M is small, there is a continuous depinning transition from a small- F
      static phase to a large- F moving phase. When M is increased to M(c), a novel
      tricritical point occurs. For M>M(c), the depinning transition becomes
      discontinuous with hysteresis. Yet, the distribution of discrete "avalanche"-like
      events as the force is increased in the static phase for M>M(c) has an unusual
      mixture of first-order-like and critical features. The results may be relevant
      for the onset of crack propagation and for dynamics of geological faults.

PMID- 11531585
TI  - Quantum pump for spin and charge transport in a Luttinger liquid.
AB  - We study two different parametric pumps--one for pumping spin currents, the other
      for charge currents--in interacting quantum wires. We find that, as a function of
      pumping frequency, the spin or charge pumped per cycle has a nonuniversal
      crossover--depending on pumping details--between two universal fixed point values
      of 0 and twice the electronic spin or charge quantum number. The direction of
      flow between these two fixed points depends on whether the interactions are
      repulsive or attractive, while the quantization itself is a signature of
      interactions.

PMID- 11531586
TI  - Noncontact friction and force fluctuations between closely spaced bodies.
AB  - Noncontact friction between a Au(111) surface and an ultrasensitive gold-coated
      cantilever was measured as a function of tip-sample spacing, temperature, and
      bias voltage using observations of cantilever damping and Brownian motion. The
      importance of the inhomogeneous contact potential is discussed and comparison is
      made to measurements over dielectric surfaces. Using the fluctuation-dissipation
      theorem, the force fluctuations are interpreted in terms of near-surface
      fluctuating electric fields interacting with static surface charge.

PMID- 11531587
TI  - Exclusion of quantum coherence as the origin of the 2D metallic state in high
      mobility silicon inversion layers.
AB  - The temperature and density dependence of the phase coherence time tau(phi) in
      high-mobility silicon inversion layers was determined from the magnetoresistivity
      due to weak localization. The upper temperature limit for single-electron quantum
      interference effects was delineated by comparing tau(phi) with the momentum
      relaxation time tau. A comparison between the density dependence of the borders
      for quantum interference effects and the strong resistivity drop reveals that
      these effects are not related to each other. As the strong resistivity drop
      occurs in the Drude regime, the apparent metallic behavior cannot be caused by
      quantum coherent effects.

PMID- 11531588
TI  - Even-odd behavior of conductance in monatomic sodium wires.
AB  - With the aid of the Friedel sum rule, we perform first-principles calculations of
      conductances through monatomic Na wires, taking into account the sharp tip
      geometry and discrete atomic structure of electrodes. We find that conductances
      (G) depend on the number (L) of atoms in the wires; G is G(0)( = 2e(2)/h) for odd
      L, independent of the wire geometry, while G is generally smaller than G(0) and
      sensitive to the wire structure for even L. This even-odd behavior is attributed
      to the charge neutrality and resonant character due to the sharp tip structure.
      We suggest that similar even-odd behavior may appear in other monovalent atomic
      wires.

PMID- 11531589
TI  - Josephson effect in MgB(2) break junctions.
AB  - We present the first observation of the dc and ac Josephson effect in MgB(2)
      break junctions. The junctions, obtained at 4.2 K in high-quality, high-density
      polycrystalline metallic MgB(2) samples, show a nonhysteretic dc Josephson
      effect. By irradiating the junctions with microwaves we observe clear Shapiro
      steps spaced by the ideal Delta V value. The temperature dependence of the dc
      Josephson current and the dependence of the height of the steps on the microwave
      power are obtained. These results directly prove the existence of pairs with
      charge 2e in MgB(2) and give evidence of the superconductor-normal metal
      superconductor weak link character of these junctions.

PMID- 11531590
TI  - Scaling near the quantum-critical point in the SO(5) theory of the high-T(c)
      superconductivity.
AB  - We study the quantum-critical point scenario within the unified theory of
      superconductivity and antiferromagnetism based on the SO(5) symmetry. Closed-form
      expression for the quantum-critical scaling function for the dynamic spin
      susceptibility is obtained from the lattice SO(5) quantum nonlinear sigma-model
      in three dimensions, revealing that in the quantum-critical region the frequency
      scale for spin excitations is simply set by the absolute temperature.
      Implications for the non-Fermi liquid behavior of the normal-state resistivity
      due to spin fluctuations in the quantum-critical region are also presented.

PMID- 11531560
TI  - Observation of CP violation in the B(0) meson system.
AB  - We present an updated measurement of time-dependent CP-violating asymmetries in
      neutral B decays with the BABAR detector at the PEP-II asymmetric B Factory at
      SLAC. This result uses an additional sample of Upsilon(4S) decays collected in
      2001, bringing the data available to 32 x 10(6) BB macro pairs. We select events
      in which one neutral B meson is fully reconstructed in a final state containing
      charmonium and the flavor of the other neutral B meson is determined from its
      decay products. The amplitude of the CP-violating asymmetry, which in the
      standard model is proportional to sin2 beta, is derived from the decay time
      distributions in such events. The result sin2 beta = 0.59+/-0.14(stat)+/
      0.05(syst) establishes CP violation in the B(0) meson system. We also determine
      absolute value of lambda = 0.93+/-0.09(stat)+/-0.03(syst), consistent with no
      direct CP violation.

PMID- 11531591
TI  - Optical conductivity and penetration depth in MgB(2).
AB  - The complex conductivity of a MgB(2) film has been investigated in the frequency
      range 4<nu<30 cm(-1) and for temperatures 2.7<T<300 K. The overall temperature
      dependence of both components of the complex conductivity is reminiscent of BCS
      type behavior, although a detailed analysis reveals a number of discrepancies. A
      peak in the temperature dependence of the real part of the conductivity is
      detected for frequencies below 9 cm(-1). The superconducting penetration depth
      follows a T(2) behavior at low temperatures.

PMID- 11531593
TI  - Resonating valence bond wave functions for strongly frustrated spin systems.
AB  - The resonating-valence-bond (RVB) theory for two-dimensional quantum
      antiferromagnets is shown to be the correct paradigm for large enough "quantum
      frustration." This scenario, proposed a long time ago but never confirmed by
      microscopic calculations, is strongly supported by a new type of variational wave
      function, which is extremely close to the exact ground state of the J(1)-J(2)
      Heisenberg model for 0.4 less than approximately J(2)/J(1) less than
      approximately 0.5. This wave function is proposed to represent the generic spin
      half RVB ground state in spin liquids.

PMID- 11531592
TI  - Fluctuation dominated Josephson tunneling with a scanning tunneling microscope.
AB  - We demonstrate Josephson tunneling in vacuum tunnel junctions formed between a
      superconducting scanning tunneling microscope tip and a Pb film, for junction
      resistances in the range 50-300 k Omega. We show that the superconducting phase
      dynamics is dominated by thermal fluctuations, and that the Josephson current
      appears as a peak centered at small finite voltage. In the presence of microwave
      fields ( f = 15.0 GHz) the peak decreases in magnitude and shifts to higher
      voltages with increasing rf power, in agreement with theory.

PMID- 11531594
TI  - Multichannel pseudogap Kondo model: large-N solution and quantum-critical
      dynamics.
AB  - We discuss a multichannel SU(N) Kondo model which displays nontrivial zero
      temperature phase transitions due to a conduction electron density of states
      vanishing with a power law at the Fermi level. In a particular large- N limit,
      the system is described by coupled integral equations corresponding to a dynamic
      saddle point. We exactly determine the universal low-energy behavior of spectral
      densities at the scale-invariant fixed points, obtain anomalous exponents, and
      compute scaling functions describing the crossover near the quantum-critical
      points. We argue that our findings are relevant to recent experiments on impurity
      doped d-wave superconductors.

PMID- 11531595
TI  - Magnetization plateaus of SrCu(2)(BO(3))(2) from a Chern-Simons theory.
AB  - The antiferromagnetic Heisenberg model on the frustrated Shastry-Sutherland
      lattice is studied by a mapping onto spinless fermions carrying one quantum of
      statistical flux. Using a mean-field approximation these fermions populate the
      bands of a generalized Hofstadter problem. Their filling leads to the
      magnetization curve. For SrCu(2)(BO(3))(2) we reproduce plateaus at 1/3 and 1/4
      of the saturation moment and predict a new one at 1/2. Gaussian fluctuations of
      the gauge field are shown to be massive at these plateau values.

PMID- 11531596
TI  - Electronic and magnetic structures of Sr(2)FeMoO(6).
AB  - We have investigated the electronic and magnetic structures of Sr(2)FeMoO(6)
      employing site-specific direct probes, namely x-ray absorption spectroscopy with
      linearly and circularly polarized photons. In contrast to some previous
      suggestions, the results clearly establish that Fe is in the formal trivalent
      state in this compound. With the help of circularly polarized light, it is
      unambiguously shown that the moment at the Mo sites is below the limit of
      detection (<0.25 mu(B)), resolving a previous controversy. We also show that the
      decrease of the observed moment in magnetization measurements from the
      theoretically expected value is driven by the presence of mis-site disorder
      between Fe and Mo sites.

PMID- 11531597
TI  - Tunnel window's imprint on dipolar field distributions.
AB  - We have performed Monte Carlo simulations of interacting dipoles that relax
      through quantum tunneling. We aim to mimic tunneling experiments on crystals of
      magnetic clusters, such as Fe(8), at very low temperatures. Accordingly, we allow
      spin flips only if the corresponding energy change is less than some 2 delta
      h(hf). Time evolutions of the dipolar field distribution P(t)(H) are studied. As
      in experiments, a "hole" develops in P(t)(H). The half-width W of incipient holes
      of weakly polarized systems are, under certain conditions, simply related to
      delta h(hf). For k(B)T less than approximately 0.5 delta h(hf) and delta h(hf)
      smaller than approximately 1/10 of the half-width of the dipolar field
      distributions of disordered systems, W approximately equal to 0.75 delta h(hf).

PMID- 11531598
TI  - Nonadiabatic conditional geometric phase shift with NMR.
AB  - A conditional geometric phase shift gate, which is fault tolerant to certain
      types of errors due to its geometric nature, was realized recently via nuclear
      magnetic resonance (NMR) under adiabatic conditions. However, in quantum
      computation, everything must be completed within the decoherence time. The
      adiabatic condition makes any fast conditional Berry phase (cyclic adiabatic
      geometric phase) shift gate impossible. Here we show that by using a newly
      designed sequence of simple operations with an additional vertical magnetic
      field, the conditional geometric phase shift gate can be run nonadiabatically.
      Therefore geometric quantum computation can be done at the same rate as usual
      quantum computation.

PMID- 11531599
TI  - Solid-state quantum computer based on scanning tunneling microscopy.
AB  - We propose a solid-state nuclear-spin quantum computer based on application of
      scanning tunneling microscopy (STM) and well-developed silicon technology. It
      requires the measurement of tunneling-current modulation caused by the Larmor
      precession of a single electron spin. Our envisioned STM quantum computer would
      operate at the high magnetic field (approximately 10 T) and at low temperature
      approximately 1 K.

PMID- 11531600
TI  - Array-enhanced coherence resonance: nontrivial effects of heterogeneity and
      spatial independence of noise.
AB  - We demonstrate the effect of coherence resonance in a heterogeneous array of
      coupled Fitz Hugh-Nagumo neurons. It is shown that coupling of such elements
      leads to a significantly stronger coherence compared to that of a single element.
      We report nontrivial effects of parameter heterogeneity and spatial independence
      of noise on array-enhanced coherence resonance; especially, we find that (i) the
      coherence increases as spatial correlation of the noise decreases, and (ii)
      inhomogeneity in the parameters of the array enhances the coherence. Our results
      have the implication that generic heterogeneity and background noise can play a
      constructive role to enhance the time precision of firing in neural systems.

PMID- 11531601
TI  - Shear-induced nano-macro structural transition in a polymeric bicontinuous
      microemulsion.
AB  - Bicontinuous microemulsions arise in a narrow concentration range for ternary
      blends containing two immiscible homopolymers and the corresponding diblock
      copolymer. Steady shear reveals four distinct regimes of response as a function
      of shear rate, corresponding to flow-induced transitions in fluid structure. In
      situ neutron scattering shows flow-induced anisotropy in the nanometer-scale
      microemulsion structure at moderate shear rates, while higher rates induce bulk
      phase separation, with micron-size morphology, which is characterized with in
      situ light scattering and optical microscopy.

PMID- 11531602
TI  - Phase-morphology map of polymer-blend thin films confined to narrow strips.
AB  - Upon lateral confinement, a critical polymer-blend film at 200 degrees C has been
      directed to form tube, capsule, confined domain, and multiple domain
      configurations. A phase-morphology map is produced by varying the confinement
      width ( W) and film thickness ( h(0)), and interpreted using a single pore model.
      Using the known correlation length, capsule length, and W, the boundary, in terms
      of W/h(0), between configurations is predicted and found to be in good agreement
      with experiment. This morphology map has potential applications for
      microencapsulating drugs and self-assembled conducting wires.

PMID- 11531603
TI  - Equilibrium configurations and energetics of point defects in two-dimensional
      colloidal crystals.
AB  - We demonstrate a novel method of introducing point defects (mono- and
      divacancies) in a confined monolayer colloidal crystal by manipulating individual
      particles with optical tweezers. Digital video microscopy is used to study defect
      dynamics in real space and time. We verify the numerical predictions that the
      stable configurations of the defects have reduced symmetry compared to the
      triangular lattice and discover that in addition they are characterized by
      distinct topological arrangements of the particles in the defect core.
      Surprisingly, point defects are thermally excited into separated dislocations,
      from which we extract the dislocation pair potential.

PMID- 11531604
TI  - Droplet growth by coalescence in binary fluid mixtures.
AB  - The evolution of the drop-size distribution in immiscible fluid mixtures
      following well-specified shear histories is investigated by in situ microscopy,
      allowing determination of the shear-induced coalescence efficiency epsilon. At
      small capillary number Ca, epsilon is constant, whereas at larger values of Ca,
      epsilon decreases, in agreement with theory accounting for slight deformation of
      the drops in close approach. Coalescence causes the drop-size distribution to
      broaden in general, but greater deformation of the larger drops at high shear
      rates causes the drop-size distribution to remain narrow.

PMID- 11531605
TI  - Comment on "Silicon clathrate with an f-electron system".

PMID- 11531607
TI  - Alzheimer's disease and estrogen replacement therapy--where are we now?

PMID- 11531608
TI  - Iron supplementation in pregnancy--evidence and controversies.
AB  - Approximately 20% of women in industrialized countries have iron deficiency in
      pregnancy. This article focuses on the diagnostic problem of anemia and iron
      deficiency and discusses different strategies for iron supplementation in
      pregnancy. S-ferritin is commonly used to diagnose empty iron stores and is
      considered useful early in pregnancy as a diagnostic tool. Mean cellular volume
      (MCV), s-Fe and erythrocyte distribution width is too unspecific. Serum
      transferrin receptor (sTfR) is a relatively novel promising indicator of iron
      deficiency. Iron demands of the pregnant women are discussed as well as the
      dietary content of iron. Both beneficial and adverse effects of iron
      supplementation are outlined. It is not documented that supplementation has any
      substantial effect on birth weight or various complications in pregnancy.
      However, supplementation corrects the iron store and biochemical parameters of
      iron deficiency including hemoglobin concentration (Hb) and maintains the
      maternal iron stores in the puerperium. Recent literature also suggests that iron
      supply to the pregnant women may have beneficial effects on the iron content of
      neonates the first year of life.

PMID- 11531609
TI  - Clinical management of PCOS.
AB  - The polycystic ovary syndrome (PCOS) is a heterogeneous condition with genetic
      predisposition. It is characterized by a myriad of symptoms including
      oligomenorrhea or amenorrhea, anovulation or infertility, hirsutism or acne.
      Insulin resistance appears to be an important factor in PCOS though the lack of
      an etiology has led to symptom oriented therapy which includes lifestyle
      modification, the use of cyclical progestagens and antiandrogens. Ovulation
      induction by drug therapy and ovarian drilling aims to treat subfertility in
      women with PCOS. Therapeutic approaches to PCOS remain an ongoing source of
      debate. Insulin sensitizing agents may bring new hope in therapy. Future research
      is aimed at shedding light on the pathophysiology so as to optimize treatment of
      women with PCOS.

PMID- 11531610
TI  - Effects of erythromycin on stretch-induced contractile activity of isolated
      myometrium from pregnant women.
AB  - BACKGROUND: Despite the fact that preterm labor and birth account for the vast
      majority of neonatal morbidity and mortality the currently available treatment
      options are still far from satisfactory. The aim of this study was to investigate
      the effects of erythromycin on stretch-induced contractions of pregnant human
      myometrial strips, obtained at cesarean section. METHOD: Myometrial strips were
      suspended in an organ bath under 3 g tension and the effects of erythromycin
      (0.1, 0.2, 0.5, 1.0 mM) on stretch-induced isometric contractions were evaluated.
      Results were statistically analyzed using Kruskal Wallis analysis of variance and
      Wilcoxon Rank tests where appropriate. RESULTS: Erythromycin caused a significant
      decrease in the peak amplitude, while causing an increase in frequency of stretch
      induced myometrial contractions in a dose dependent manner in vitro. CONCLUSIONS:
      Results from this preliminary study suggest that erythromycin may have additional
      beneficial effects in infection related preterm labor cases, however, further
      studies are needed for clarifying the usefulness of erythromycin as a tocolytic
      agent.

PMID- 11531611
TI  - Doppler assessment of umbilical artery, thoracic aorta and middle cerebral artery
      in the management of pregnancies with growth restriction.
AB  - BACKGROUND: The aim of the study was to determine the best use of information
      obtained from Doppler studies of umbilical artery, thoracic aorta and middle
      cerebral artery in the management of pregnancies with growth restriction.
      METHODS: The study group consisted of 100 pregnant women with intrauterine growth
      restricted fetuses. Doppler flow velocity waveforms were obtained from the
      umbilical artery, middle cerebral artery and thoracic aorta. The pregnancies were
      grouped according to the umbilical artery Doppler results. There were 29, 30 and
      41 fetuses with normal and high PI (pulsatility index), and absent end-diastolic
      velocity (AEDV) in the umbilical artery, respectively. RESULTS: Birth weight and
      umbilical vein pH at birth significantly decreased and perinatal mortality rates
      significantly increased with the worsening of the diastolic flow in the umbilical
      artery (p<0.01). Increased umbilical artery PI was significantly associated with
      increased thoracic aorta PI and decreased middle cerebral artery PI (r=0.75 and 
      0.55, p<0.01 respectively). Perinatal mortality due to fetal asphyxia in fetuses
      with AEDV in the umbilical artery and in both the umbilical artery and thoracic
      aorta was 39.5% and 50%, respectively. Detection of AEDV in the thoracic aorta
      was found to be the most significant predictive factor of perinatal deaths.
      CONCLUSIONS: The degree of abnormality of the Doppler findings parallels the
      severity of fetal compromise. Growth restricted fetuses with AEDV detected both
      in the umbilical artery and thoracic aorta are severely compromised and time
      gained in utero has no benefit for these fetuses.

PMID- 11531612
TI  - Women with a history of placental abruption: when in a subsequent pregnancy
      should special surveillance for a recurrent placental abruption be initiated?
AB  - BACKGROUND: It is common to admit to hospital or start intensive ambulatory
      antenatal care of pregnant women with a previous placental abruption using the
      gestational age of the previous placental abruption as a starting point. In some
      instances, close surveillance may be commenced much earlier. There is no
      consensus when in a subsequent pregnancy such measures should be initiated.
      OBJECTIVE: The analyses aimed at the prevention of complicated (preterm, small
      for gestational age, or perinatal death) recurrent placental abruptions,
      assessing at which time in a subsequent pregnancy special surveillance should
      start in order to anticipate and prevent a recurrence. DESIGN: A cohort study
      based on the Medical Birth Registry of Norway. Calculation of gestational age
      specific risks of placental abruption in a second pregnancy and estimation of
      when to initiate surveillance in order to reduce an increased risk of recurrent
      placental abruption to the initial level of initial abruption in the second
      pregnancy. RESULTS: In women with a complicated (preterm, small for gestational
      age, or perinatal death) first delivery, the risks of an initial and recurrent
      complicated placental abruption in the second pregnancy were 7/1000 and 33/1000,
      respectively (relative risk 4.9). To reduce the recurrence risk in a second
      pregnancy to 7/1000, special surveillance six weeks prior to the gestational age
      of the initial abruption would be necessary. In women with an uncomplicated first
      delivery, the risks in the second pregnancy of an initial and recurrent
      complicated abruption were 3 and 19/1000, respectively (relative risk 7.1). To
      reduce the recurrence risk to 3/1000, surveillance at least 12 weeks prior would
      be necessary. CONCLUSION: The increased recurrence rate would necessitate
      increased awareness in terms of special surveillance in the second pregnancy. In
      pregnancies at risk of a recurrent placental abruption, monitoring up to three
      months before the gestational age of the initial abruption is necessary.

PMID- 11531613
TI  - Feto-maternal morbidity and mortality after cardiac valve replacement.
AB  - BACKGROUND: The aim of this study is to evaluate the fetomaternal morbidity and
      mortality of the pregnancies of women who conceived after cardiac valve
      replacement. METHODS: A consecutive series of one hundred and thirty-six
      pregnancies of one hundred and one patients who conceived after cardiac valve
      replacement were retrospectively analyzed. Regarding the anticoagulation therapy,
      101 patients were classified into three groups: A: patients on oral
      anticoagulants (n=68), B: patients on heparin (n=16) and C: patients who received
      no anticoagulation (n=17). RESULTS: Three groups (patients on oral anticoagulants
      (A), on heparin (B), patients who received no anticoagulation (C)) were compared
      in terms of spontaneous abortion (19%, 11%, 5.6%), preterm delivery (14%, 22.3%,
      16.6%), maternal mortality (3%, 11.1%, 0%), thromboembolic events (4%, 11.1%,
      0%), cardiac failure (6%, 11.1%, 11.1%), atrial fibrillation (9%, 11.1%, 5.6%),
      antenatal bleeding (9%, 11.1%, 5.6%), delivery route and fetal malformation (5%,
      0%, 0%) and no statistically significant differences were detected. In group B,
      hematoma formation rate (22.2%) (p=0.011) and transfusion rate (27.8%) (p=0.005)
      were significantly higher. Five cases of congenital anomalies were detected, all
      belonging to group A, but this tendency was not found to be statistically
      significant. CONCLUSIONS: Management of pregnancies with prosthetic heart valves
      require closely monitored anticoagulation, and an obstetrician should be familiar
      with the potential fetal and maternal adverse effects of any anticoagulant
      therapy during the course of pregnancy.

PMID- 11531614
TI  - Oxidative stress in pre-eclampsia.
AB  - BACKGROUND: The objective of this study was to test the hypothesis that maternal
      plasma, cord plasma and placental tissue lipid peroxidation products are
      increased and antioxidants are decreased in women with pre-eclampsia. METHODS:
      Placenta, maternal and cord plasma were collected at delivery from 29 normal, 21
      pre-eclamptic and six eclamptic women. Plasma was collected from 21 non-pregnant
      matched controls. The analyses were measured by HPLC and colorimetric assay.
      RESULTS: Plasma maternal concentrations of uric acid, LPO, MDA, ascorbic acid,
      vitamin E and cholesterol were not significantly different in pre-eclampsia as
      compared with normal pregnancy. Plasma concentrations of ascorbic acid and
      vitamin E were not significantly different in normal pregnancy as compared with
      the non-pregnant controls. Cord plasma concentrations of MDA were significantly
      higher in eclampsia (1.16+/-0.26 micromol/l) as compared with normal pregnancy
      (0.79+/-0.05 micromol/l, p<0.02) and pre-eclampsia (0.83+/-0.05 micromol/l,
      p<0.05). Cord plasma concentrations of vitamin E were significantly higher in
      eclampsia (21.3+/-7.5 micromol/l) as compared with normal pregnancy (10.2+/-1.1
      micromol/l, p<0.01) and pre-eclampsia (10.4+/-1.8 micromol/l, p<0.04). Placental
      concentrations of LPO, MDA and ascorbic acid were not significantly different in
      pre-eclampsia as compared with normal pregnancy. Plasma cord concentrations of
      LPO and placental concentrations of vitamin E were undetected for normal
      pregnant, pre-eclamptic and eclamptic women respectively. Uric acid
      concentrations were significantly increased in eclampsia as compared with the non
      pregnant controls (p<0.0001), normal pregnant controls (p<0.0001) and pre
      eclampsia (p<0.008). CONCLUSIONS: The findings in this study do not show any
      evidence of deficiency in the maternal protective antioxidant systems or
      increased production of lipid peroxidation products, LPO and MDA in African women
      with pre-eclampsia as compared with normal pregnancy. However, there was evidence
      of increased cord plasma concentrations of MDA and vitamin E in eclampsia as
      compared with normal pregnancy and pre-eclampsia. The placenta may be effective
      in removing MDA. The antioxidant uric acid serves as a protective role whilst the
      antioxidant and oxidant capacity in the different study groups remained
      unchanged.

PMID- 11531615
TI  - Analysis of outcome in hydrops fetalis in relation to gestational age at
      diagnosis, cause and treatment.
AB  - OBJECTIVE: To examine fetal outcome in hydrops fetalis in relation to gestational
      age at diagnosis and following investigation and treatment. METHODS: All cases of
      hydrops fetalis presenting to the Fetal Medicine Unit during the last seven
      years, between 1993 and 1999, were identified from the Fetal Medicine Database.
      During this time 87 of 13,980 patients who attended the Fetal Medicine Unit had
      hydrops fetalis. The cases were examined for gestational age at presentation
      according to etiology and fetal survival following investigation and treatment.
      The fetal survival rates for non-immune cases of hydrops before and after 24
      weeks were compared. RESULTS: The cause of hydrops was determined antenatally in
      71 of the 87 (82%) cases. Of the 51 cases presenting before 24 weeks' gestation,
      23 (45%) were due to chromosomal abnormality. After 24 weeks, fetal
      tachyarrhythmias and hydrothorax were the most common causes and accounted for 14
      (38%) of the 36 cases. Thirty-four cases (39%) of hydrops received intrauterine
      treatment. The survival rates excluding chromosomal abnormalities in the non
      immune cases before and after 24 weeks' gestation were 31% and 48%, respectively,
      and were not significantly different. CONCLUSIONS: The survival rate in cases of
      hydrops fetalis may be improved with appropriate prenatal investigation and
      therapy. The etiology of hydrops is different before and after 24 weeks, and even
      when cases of chromosomal abnormality are excluded the survival rate is similar
      before and after 24 weeks.

PMID- 11531616
TI  - Mode of delivery in breech presentation at term: increased neonatal morbidity
      with vaginal delivery.
AB  - OBJECTIVE: To compare the neonatal outcome in planned vaginal delivery and
      planned cesarean section in term singleton pregnancies with breech presentation
      in a Scandinavian clinic with a high rate of vaginal breech delivery. METHODS: A
      retrospective study including 1050 term singleton breech pregnancies delivered at
      a Swedish tertiary referral center during 1988 to 2000. For 699 patients (67%) a
      vaginal delivery was planned, of whom 603 (86%) were delivered vaginally. In 327
      (31%) cases a cesarean section was planned and performed. These two groups were
      compared regarding rates of acidemia at birth (cord artery pH <7.05), low Apgar
      scores and neonatal neurological morbidity. Long term sequels among infants with
      a complicated neonatal course were also identified. RESULTS: Acidemia at birth,
      Apgar score below 7 at 5 minutes, and referral to neonatal intensive care unit
      all occurred at higher rates in planned vaginal delivery (5.3%, 3.6%, and 8.9%,
      respectively), than in planned cesarean delivery (0, 0, and 4.0%). The rate of
      neonatal neurological morbidity was 24/699 (3.4%) in planned vaginal delivery (18
      cases with cerebral symptoms and six cases of brachial plexus palsy) compared to
      one case (cerebral symptoms) after a planned cesarean. These differences were all
      statistically significant (p< or =0.002). Of the neurologically affected
      neonates, two died and four had cerebral palsy (one delivered by planned cesarean
      section) at follow up. CONCLUSION: Neonatal morbidity may be reduced with planned
      cesarean delivery in breech presentation, also in a Scandinavian setting.

PMID- 11531617
TI  - Labor admission test: an assessment of the test's value as screening for fetal
      distress in labor.
AB  - BACKGROUND: To determine if the labor admission test (LAT) can predict fetal
      distress in a population of laboring women, and in subgroups of low- or high-risk
      women, who delivered within six hours or between six and 24 hours after LAT.
      METHODS: The data charts of all women who delivered at Hammerfest Hospital in
      1996, 1997 and 1998 were retrospectively read. If the woman was admitted to the
      hospital because of onset of labor, was in the first stage of labor and delivered
      within 24 hours after admission, she was included. In the study period, 1639 gave
      birth and 932 were included in the study. A descriptive analysis of the
      population and assessment of LAT's sensitivity, positive predictive value,
      specificity and negative predictive value at different cut-off values was done.
      RESULTS: In the study population 5.8% had fetal distress, and 5.3% had an
      operative delivery because of fetal distress. LAT's sensitivity in the whole
      population was 0.15 and positive predictive value was 0.16. Specificity was 0.95
      and positive predictive value was 0.95. In the subgroups of low- and high-risk
      women, who delivered within six hours or between six and 24 hours after LAT,
      sensitivity varied between 0 and 0.36, and positive predictive value varied
      between 0 and 0.27. Specificity varied between 0.92 and 0.96, and negative
      predictive value varied between 0.89 and 0.97. CONCLUSIONS: According to these
      results, LAT cannot be recommended as a screening test for fetal distress in
      labor in low-risk women. Sensitivity is too low, and there are too many false
      positive tests. It is unclear if LAT has benefits among high-risk women.

PMID- 11531618
TI  - Clinical and pregnancy outcome following ectopic pregnancy; a prospective study
      comparing expectancy, surgery and systemic methotrexate treatment.
AB  - BACKGROUND: The improved possibility of an early diagnosis of ectopic pregnancy
      by use of serial quantitative beta-subunit human chorionic gonadotropin hormone
      levels together with transvaginal ultrasound has opened up options for
      conservative treatment. Systemic methotrexate treatment of unruptured ectopic
      pregnancy has emerged as a safe and effective alternative to surgical procedures.
      The aim of the present study was to investigate the effectiveness of methotrexate
      treatment in routine clinical practice, but also to assess pregnancy outcome
      during a 2.5-year follow-up period. METHODS: All patients presenting to the
      Department of Obstetrics and Gynecology, Umea University Hospital, with signs and
      symptoms of ectopic pregnancy between January 1, 1995 and December 31, 1997 were
      included in this prospective study. Patients with ectopic pregnancy were either
      managed expectantly, treated with methotrexate or by laparoscopic or open surgery
      (salpingostomy/salpingectomy). Systemic methotrexate (Pharmacia & Upjohn,
      Stockholm, Sweden) was administered as an intramuscular injection of 50 mg/m(2).
      RESULTS: One hundred and seven patients presented with signs and symptoms of a
      possible ectopic pregnancy, of these 89 patients eventually were diagnosed as
      having an ectopic pregnancy. Twenty-six (29%) patients were treated with
      methotrexate, 46 (52%) patients with laparoscopy or laparotomy, and 17 (19%)
      patients by expectant management. Success rate in the methotrexate group, after
      one or more injections, was 77% (20 patients out of 26). The mean time to
      resolution was 24+/-9 days. There was no difference in pregnancy rate following
      methotrexate treatment compared to surgical treatment. CONCLUSIONS: Systemic
      single-dose methotrexate treatment is a safe treatment option with a reasonably
      high success rate, with similar probability of a later intrauterine pregnancy as
      conventional surgical treatment.

PMID- 11531619
TI  - Evaluation of HPV testing by Hybrid Capture II for routine gynecologic screening.

PMID- 11531620
TI  - Antibiotic treatment for threatened abortion during the early first trimester in
      women with previous spontaneous abortion.
AB  - BACKGROUND: We retrospectively examined the usefulness of antibiotic therapy for
      management of first-trimester threatened abortion in women with previous
      spontaneous abortion. METHODS: From 1993 through 1999, women with first-trimester
      threatened abortion received antibiotic therapy. Only those with gestational age
      less than 9 weeks and previous spontaneous abortion were included in this
      analysis. Women with mild abdominal cramping received amoxicillin plus
      erythromycin for 1 week; those with severe abdominal pain received amoxicillin
      plus clindamycin for 1 week. Recurrence was documented on the basis of either
      lower abdominal pain or vaginal bleeding. RESULTS: Of the 23 women included, 15
      (65%) had abnormal vaginal flora (a score above 4, Nugent's criteria). Seven of
      16 women who received amoxicillin plus clindamycin and three of seven who
      received amoxicillin plus erythromycin had complete resolution of lower abdominal
      pain and vaginal bleeding without recurrence (p=1). The recurrence rate was
      higher, though not significantly, in women with abnormal bacterial vaginal flora
      (8/15 vs. 2/8, p=0.379). Twenty-two (96%) of the 23 pregnancies were carried to
      term, with no identifiable neonatal anomalies. CONCLUSIONS: These results suggest
      the usefulness of early antibiotic therapy in preventing pregnancy loss in women
      with threatened abortion early in the first trimester, and warrant further
      clinical trials.

PMID- 11531622
TI  - Prenatal diagnosis of intrauterine cytomegalovirus infection in a fetus with non
      immune hydrops fetalis.

PMID- 11531621
TI  - Risk for anogenital cancer and other cancer among women hospitalized with
      gonorrhea.
AB  - BACKGROUND: We investigated the relationship between infections with Neisseria
      gonorrhoeae and anogenital and other cancers. METHODS: Nationwide and population
      based register linkage study utilizing prospectively notified information. The
      observed numbers of cancers among the women were compared with those expected on
      the basis of national incidence rates. RESULTS: In a cohort of 4440 women
      hospitalized for gonorrhea we observed a total of 227 cases of cervical
      intraepithelial neoplasia grade III (CIN III), with 103 expected (standardized
      incidence ratio (SIR), 2.2; 95% confidence interval (CI), 1.9-2.5). No
      significantly increased risk for other anogenital cancers or cancer at other
      sites was seen. CONCLUSIONS: These results support the view that the observed
      association between gonorrheal infection and subsequent cervical preneoplasia is
      due mainly to surveillance bias. However, our results also indicate that women
      hospitalized with a N. gonorrhoeae infection will benefit from the compliance
      with the regular Pap smear screening programs.

PMID- 11531623
TI  - Intracranial bleed in a pregnant patient on oral anticoagulants for prosthetic
      heart valve.

PMID- 11531624
TI  - Life-threatening Clostridium difficile-associated diarrhea induced by paclitaxel
      carboplatin combination chemotherapy.

PMID- 11531625
TI  - Impaired healing of a vaginal tear in a patient with schistosomiasis.

PMID- 11531626
TI  - Hysteroscopy in 2001: a comprehensive review.

PMID- 11531627
TI  - Accuracy of outpatient endometrial biopsy in the diagnosis of endometrial
      hyperplasia.
AB  - BACKGROUND: To determine the accuracy of outpatient endometrial biopsy in
      diagnosing endometrial hyperplasia in women with abnormal uterine bleeding.
      DESIGN: Systematic quantitative review of published medical literature. DATA
      SOURCES: Relevant papers were identified through electronic scanning of MEDLINE
      (1980-1999) and EMBASE (1980-1999), manual searching of bibliography of known
      primary and review articles and contact with manufacturers. REVIEW METHODS:
      Studies were selected if accuracy of outpatient endometrial biopsy, in women with
      abnormal pre or postmenopausal uterine bleeding, was estimated compared to a
      reference standard, which was endometrial histology obtained by tissue sampling
      under anesthesia. Quality assessment and data extraction were performed in
      duplicate. Diagnostic accuracy was determined by pooled likelihood ratios (LR)
      for positive and negative test results for endometrial hyperplasia. RESULTS:
      There were 881 subjects in 8 diagnostic evaluations reported in 6 primary
      studies. Postmenopausal women represented 25% of the participants studied. There
      were 43 patients in whom outpatient sampling was inadequate. A positive test
      result on outpatient biopsy diagnosed endometrial hyperplasia with a pooled LR of
      12.0 (95% CI 7.8-18.6) while a negative test result had a pooled LR of 0.2 (95%
      CI 0.1-0.3). With a positive test result, the posttest probability of endometrial
      hyperplasia was 57.7% (95% CI 41.1%-72.7%) while it was 2.2% (95% CI 0.9%-4.1%)
      with a negative test. CONCLUSION: Outpatient endometrial biopsy has modest
      accuracy in diagnosing endometrial hyperplasia. Therefore, additional endometrial
      assessment should be undertaken, especially if symptoms persist or intrauterine
      structural abnormalities are suspected.

PMID- 11531628
TI  - Fertility preservation in gynecologic cancer.
AB  - SUBJECT: Management of patients with gynecologic cancer can now often be tailored
      to the extent of the disease and preservation of child-bearing ability and/or
      sexual function may be possible for certain women with early invasive disease.
      METHOD: A better understanding of the tumor-biology, and the consideration of
      different clinicopathologic factors, that bear prognostic significance in
      therapeutic modalities, will allow more and more individualization of treatment.
      DISCUSSION: Management of young women with early gynecologic cancer should
      therefore be individualized with the risk of conservative therapy balanced
      against the dangers and advantages of more radical therapy. Experts in
      gynecologic oncology and infertility together with an informed patient and her
      family should make treatment decisions. OUTCOME: This article will review the
      conservative surgical management of early invasive cancers of the ovary, cervix
      and endometrium, in order to help preserve child-bearing capacity. In addition,
      management of gynecologic cancers diagnosed during pregnancy will also be
      discussed.

PMID- 11531629
TI  - Association of polymorphism of methylene-tetrahydro-folate-reductase with urinary
      albumin excretion rate in type 1 diabetes mellitus but not with preeclampsia,
      retinopathy, and preterm delivery.
AB  - AIM: The genetic setting is a potential risk factor for dysfunction of vascular
      endothelial cells. The prevalence of polymorphism in the methylene-tetrahydro
      folate-reductase (MTHFR) gene (677C-->T) was evaluated in diabetic pregnancy
      complicated by preeclampsia, nephropathy, retinopathy, and preterm delivery. The
      role of hyperhomocysteinemia in microangiopathy in diabetes mellitus has been
      debated and is mainly seen with reduced activity of the MTHFR gene. A
      polymorphism in the gene for MTHFR is identified causing this phenomenon. DESIGN:
      Two hundred and sixty-eight pregnant women with type 1 diabetes mellitus were
      recruited. Two hundred and thirty-three women were successfully analyzed for
      MTHFR gene polymorphism 677C-->T and compared to the incidence of the
      polymorphism in the background population (n=1084). The pregnancy data charts
      were reviewed retrospectively. RESULTS: The frequency of the MTHFR polymorphism
      in the background population was 29% and the heterozygozity 42%. The women with
      type 1 diabetes mellitus had a higher frequency of the MTHFR polymorphism with
      52% heterozygotes and 9% homozygotes than had the background population
      (heterozygotes, background vs. type 1 diabetes mellitus: chi(2)=14, df=1,
      p<0.0002). The odds ratio for heterozygozity of the MTHFR polymorphism was 1.8
      (95% Cl: 1.3-2.4) in women with type 1 diabetes mellitus. Women with either micro
      or macroalbuminuria had a higher frequency of MTHFR polymorphism with 61%
      heterozygotes and 3% homozygotes than had the background population
      (heterozygotes: chi(2)=8.9, df=1, p<0.01). The odds ratio for heterozygozity of
      the MTHFR polymorphism was 2.3 (95% CI: 1.4-4) in women with type 1 diabetes
      mellitus. CONCLUSION: An association was demonstrated between the MTHFR
      polymorphism and type 1 diabetes mellitus as well as increasing albumin excretion
      rate in pregnant women.

PMID- 11531630
TI  - Increased tissue concentrations of arachidonic acid in umbilical artery and
      placenta in fetal growth retardation.
AB  - OBJECTIVE: To compare the fatty acid phospholipid composition of the umbilical
      artery and the placenta in cases of fetal growth retardation (FGR) and of normal
      growth, as well as in symmetric and asymmetric FGR. DESIGN: Case-control study.
      SETTING: University hospital. POPULATION: Thirty-nine FGR cases (12 asymmetric,
      27 symmetric) and 78 cases with normal growth. MAIN OUTCOME MEASURES: Thin layer
      gas-liquid capillary chromatography of phospholipid fatty acids in umbilical
      artery and placental cotyledons. Newborns were classified as FGR if their weight
      was under the 10th percentile for our center. FGR was defined as symmetric if the
      ponderal index was >2.32, and as asymmetric if it was <2.32. RESULTS: In FGR,
      arachidonic acid was significantly increased both in placenta (24.05%+/-2.78 vs
      22.46%+/-2.93) and in umbilical artery (16.76%+/-2.40 vs 15.58%+/-3.67). Indeed
      this increase was significantly higher in asymmetric than in symmetric FGR
      (25.70+/-2.32 vs 23.32+/-2.68 in placenta and 18.06+/-1.46 vs 16.14 +/-2.53 in
      umbilical artery). On the other hand, in the placenta there were a number of
      differences in the metabolic ratios analyzed when comparing symmetric and
      asymmetric FGR, indicating a lower DHA availability and a higher n-6 fatty acid
      elongation and desaturation in asymmetric FGR. CONCLUSION: FGR is characterized
      by an increase in arachidonic acid both in the placenta and umbilical artery
      phospolipids, probably reflecting a different mobilization from tissue stores. It
      is speculated that the different arterial composition could be partially
      responsible for the increased cardiovascular risk of FGR in adulthood. On the
      other hand the metabolic status of the placenta concerning polyunsaturated fatty
      acids was very different in symmetric and asymmetric FGR, suggesting a different
      pathogenesis.

PMID- 11531631
TI  - The significance of asymptomatic bacteremia for the newborn.
AB  - BACKGROUND: So far, there has been no systematic detection of asymptomatic
      bacteremia in pregnant women. Consequently, its possible effects on newborn
      infants have not been discussed. The aim of this study was to determine the
      incidence of asymptomatic bacteremia in pregnant and parturient women and
      neonates as well as to assess its influence on the health condition of newborn
      infants during the first three months of life. METHODS: A total of 626 blood
      cultures were taken from 353 pregnant women (with single-fetus pregnancy)and
      their newborns: 156 during pregnancy, and immediately after delivery from 235
      mothers and their 235 newborns. Blood culture results were clinically and
      statistically analyzed along with data on the development of the newborns.
      RESULTS: Positive blood culture was found in 12% of pregnant women, in 19% of
      parturient women and 25% of the newborns. The most often isolated bacteria were:
      Staphylococcus epidermidis in 36 cases (18%), Escherichia coli in 35 cases
      (17.5%) and Enterococcus in 20 cases (10%). Asymptomatic bacteremia was found to
      be in a statistically significant correlation with signs and symptoms of life
      threatening conditions (p<0.01), early-onset and late-onset infections and other
      disorders occurring in newborn infants (p<0.05), mostly of the female sex.
      CONCLUSION: It seems that asymptomatic bacteremia cannot be considered harmless
      but appears to influence the health of newborns.

PMID- 11531632
TI  - Influence of maternal magnesium sulphate and ritodrine treatment on cerebral
      blood flow velocity of the preterm newborn.
AB  - BACKGROUND: To evaluate the effect of antenatal tocolytic administration of
      magnesium sulphate and ritodrine on the cerebral blood flow velocity and on the
      cerebral vascular resistance of preterm newborns in the first hours of life.
      METHODS: Cerebral blood flow velocity, resistance index and relative vascular
      resistance were studied in 27 preterm infants (<34 weeks gestation) with
      antenatal exposure to maternal magnesium sulphate treatment and in 27 preterm
      infants (<34 weeks gestation) with antenatal exposure to maternal ritodrine
      treatment. Both antenatal magnesium sulphate or ritodrine were used for
      tocolysis. Cerebral blood flow was measured, using Doppler ultrasonography, in
      the anterior cerebral artery, in the left middle cerebral artery and in the right
      middle cerebral artery. RESULTS: We did not find any significant difference in
      the blood flow velocity, resistance index or relative vascular resistance in the
      three cerebral arteries between the two treatment groups. CONCLUSIONS: Our study
      shows that maternal antenatal administration of magnesium sulphate to delay
      preterm delivery, compared to antenatal administration of ritodrine, does not
      induce any significant differences either in cerebral blood flow velocity or in
      cerebral vascular resistance of preterm infants in the first hours of life.

PMID- 11531633
TI  - Blood pressure during pregnancy in a Swedish population; impact of parity.
AB  - SUBJECT: Hypertension represents the most commonly encountered complication of
      pregnancy. Normal levels of blood pressure (BP) need to be established in each
      pregnant population in order to recognize pathology. A lack of studies from our
      own country and certain methodological objections to early studies motivated this
      study. PATIENTS AND METHODS: Six hundred pregnant women were included in a
      historical cohort. The maternal BP had been measured with a mercury
      sphygmomanometer and standardized routines at each antenatal visit. Data
      regarding age, baseline BMI, weight gain and smoking habits as well as parity had
      been recorded. RESULTS: BP values were overall somewhat higher than in
      international studies, the SBP increasing slightly towards term. The diastolic
      blood pressure (DBP) decreased slightly until 25-28 weeks of gestation. A steady
      increase thereafter led to values at term 7.3% above initial values. In
      nulliparae the increase was significantly greater, 9.9% versus 5.4% in
      multiparae. Primigravidae showed mean DBP levels significantly higher than all
      multigravidae towards term. The DBP was correlated with the baseline BMI, but not
      with age or weight gain. In smoking pregnant women the DBP showed a significantly
      greater initial decrease and failed to follow the subsequent rise to the same
      degree as in non-smokers. CONCLUSION: Slightly higher blood pressure levels were
      found in this study compared to other international studies. Multiple regression
      analysis showed that parity, baseline BMI and smoking all significantly
      influenced the DBP at term. Multiparae have significantly lower DBP levels in
      pregnancy compared to nulliparae. The first pregnancy seems to have the greatest
      impact in lowering the blood pressure in subsequent pregnancies.

PMID- 11531634
TI  - Anal sphincter damage after vaginal delivery: functional outcome and risk factors
      for fecal incontinence.
AB  - OBJECTIVE: To assess the role of anal sphincter damage following delivery in the
      development of anorectal complaints and urinary incontinence, and to identify
      obstetric factors associated with subsequent fecal incontinence. METHODS: The
      retrospective cohort study with matched controls used a postal questionnaire and
      analysis of delivery and operation records from all women who underwent primary
      repair of a third or fourth degree perineal rupture in our hospital between 1971
      and 1991, and their controls, matched for date and parity. Frequencies of
      complaints were compared using the Mantel-Haenszel common odds ratio [OR] for
      matched-control studies. Obstetric risk factors for fecal incontinence were
      assessed with multivariate logistic regression analysis. RESULTS: In the period
      studied, 171 women underwent a primary repair. One hundred and forty-seven of
      which returned the questionnaire (86%), compared with 131 of the controls (73%).
      Analysis was performed on 125 matched pairs with a median follow-up of 14 years.
      Fecal incontinence was reported by 39 patients and 16 controls (OR: 3.09; 95%
      confidence interval: 1.57-6.10). Urinary incontinence was reported by 65 cases
      and 52 controls (OR:1.46; 95% CI: 0.91-2.37). Among women with anal sphincter
      damage, the extent of anal sphincter damage was an independent risk factor for
      fecal incontinence. (OR: 2.54; 95% CI: 1.45-4.45). Subsequent vaginal delivery
      was not associated with the development of fecal incontinence (OR: 2.32; 95% CI:
      0.85-6.33). In primiparous women mediolateral episiotomy protected for fecal
      incontinence after anal sphincter damage (OR: 0.17; 95% CI: 0.05-0.60).
      CONCLUSIONS: Anal sphincter damage following delivery is significantly associated
      with subsequent anorectal complaints, but not with urinary incontinence. The
      extent of sphincter damage is an independent risk factor for the development of
      fecal incontinence. Mediolateral episiotomy protects for fecal incontinence in
      primiparous women.

PMID- 11531635
TI  - A randomized study comparing rectally administered misoprostol versus
      Syntometrine combined with an oxytocin infusion for the cessation of primary post
      partum hemorrhage.
AB  - BACKGROUND: Post partum hemorrhage is a major cause of maternal death,
      particularly in developing countries, and most cases are due to an atonic uterus.
      Hemorrhage can occur despite active management of the third stage of labor.
      Presently, misoprostol (Cytotec, Searle Pharmaceuticals) is the only thermostable
      uterotonic agent potentially available which would be economically beneficial for
      developing countries where refrigeration of drugs poses a problem. The objective
      of the study was to compare intra-muscular Syntometrine (Sandoz Pharmaceuticals)
      (ampoule=5 iu oxytocin and 500 mcg ergometrine maleate) plus Syntocinon (Sandoz
      Pharmceuticals) (10 iu oxytocin diluted in 500 ml normal saline) intravenous
      infusion versus 800 mcg misoprostol per rectum for treatment of primary post
      partum hemorrhage in a developing country. METHODS: Randomized single blinded two
      center study, set in both a township and teaching hospital in South Africa. Sixty
      four women with primary post partum hemorrhage due to an atonic uterus were
      recruited. The primary outcome measure was whether the hemorrhage ceased within
      20 minutes of administering the first line treatment, once hemorrhage was
      clinically recognized. RESULTS: There was a 28.1% difference between the
      misoprostol arm and the Syntometrine and Syntocinon arm (p=0.01). This result had
      a greater than 80% power. Misoprostol performed better. CONCLUSION: 800 mcg
      misoprostol per rectum is effective at treating primary post partum hemorrhage.

PMID- 11531636
TI  - The relationship between cervical dilatation, interleukin-6 and interleukin-8
      during term labor.
AB  - BACKGROUND: To determine interleukin-6 and interleukin-8 levels in amniotic
      fluid, retroplacental blood and maternal serum and relate these values with
      cervical dilatation in term labor. METHODS: Prospective study. n=78 healthy women
      undergoing term cesarean section, divided into four groups: controls, n=42,
      (elective cesarean section; no contractions, membrane rupture or cervical
      dilatation); latent labor, n=12, (latent phase labor; cervix <2 cm dilated);
      established labor, n=12, (active labor, cervix 2-5 cm); advanced labor, n=12,
      (active labor, cervix >5 cm). Interleukin-6 and interleukin-8 were determined by
      ELISA (pg/ml), placenta and placental bed biopsy examined histopathologically,
      and amniotic fluid also microbiologically. Results were expressed as median and
      ranges or mean and standard deviations, as appropriate. For statistical analysis,
      Mann-Whitney U-tests or Kruskal-Wallis tests were used as applicable (Statview
      4.5). Power and linear regression analyses were performed. p<0.05 was considered
      significant, p<0.001 highly significant. RESULTS: Compared with controls, IL-6
      and IL-8 increased significantly with cervical dilatation in all compartments
      tested for almost all labor groups (p<0.05 to p<0.0001). Significant changes were
      also seen between latent and advanced labor groups in some compartments (p<0.05),
      but not between established and advanced labor groups. Intrauterine infection was
      excluded in any of the patients clinically and on histopathological or
      microbiological analysis of placentae and amniotic fluid. CONCLUSIONS: In term
      labor without intraamniotic infection, interleukin-6 and interleukin-8 at the
      fetomaternal interface and in maternal serum rise significantly with cervical
      dilatation. These cytokines could be used as markers of active labor if vaginal
      examination is not applicable.

PMID- 11531637
TI  - Factors influencing the decision to use or discard cryopreserved embryos.
AB  - BACKGROUND: Couples' reasons for discarding supernumerary fertilized
      cryopreserved embryos and gender differences in attitudes toward the frozen
      embryos were investigated among Swedish couples undergoing in vitro fertilization
      (IVF) at a private clinic. At the time of the study Swedish law stipulated that
      couples could keep their frozen embryos for a maximum of one year, with the
      possibility of an extension based on individual requests. METHODS: A
      questionnaire with structured and unstructured questions was sent to 124 women
      and 124 men who had entered the IVF treatment and obtained supernumerary embryos
      from 1 January 1994 to 1 March 1995. Eighty-two women and 74 men completed the
      questionnaire. RESULTS: After a mean storage time of 25.3 (+/-11.0) months 22
      (26.8%) of the responding couples had their embryos discarded. The reasons were
      mainly practical, such as a positive outcome of IVF and a legally too short
      storage time. Comparisons between women and men showed that fewer women
      (13;17.6%) than men (20;27%) had been uncertain during the IVF treatment about
      using the frozen embryos at a later date and that men more often than women
      expressed anxieties about possible effects of the freezing procedure on the
      potential child (p=0.009). CONCLUSION: A positive outcome of the original IVF
      treatment and a short maximum legal time of cryopreservation were the most common
      reasons why couples discarded their embryos. The men more often than women
      expressed anxieties about possible effects on a potential child. The results
      emphasize the need for giving detailed information to the couples about
      cryopreserved embryos and children born by this method.

PMID- 11531638
TI  - Transvaginal ultrasonography and hysteroscopy in postmenopausal bleeding: a
      prospective study.
AB  - OBJECTIVE: To determine the diagnostic value of transvaginal ultrasonography and
      hysteroscopy in patients with postmenopausal bleeding. MATERIAL AND METHODS:
      Between January 1, 1998 and June 30, 1999, 88 outpatient women with
      postmenopausal bleeding were enrolled in a prospective study. They underwent
      transvaginal ultrasonography and hysteroscopy, and were submitted to directed
      biopsy during hysteroscopy. Findings were classified as normal endometrium,
      suggestive of atrophy, focal abnormality (benign or suspicious), and diffuse
      thickness (benign or suspicious). Data was compared with the final diagnosis,
      established by histological examination, as atrophy, benign pathology, atypical
      hyperplasia and endometrial carcinoma. RESULTS: Among 88 women enrolled, 15 were
      excluded because hysteroscopy was impossible, and four had abandoned the study.
      The histological findings were scanty material in 12 (17.4%), atrophy in 24
      (34.8%), cystic atrophy in one (1.4%), normal endometrium in five (7.2%),
      tuberculous endometritis in one (1.4%), polyps in 12 (17.4%), leiomyoma in one
      (1.4%), non-atypical hyperplasia in three (4.3%), atypical hyperplasia in one
      (1.4%) and endometrial carcinoma in nine cases (13.0%). For the assessment of
      endometrial carcinoma, ultrasonography revealed sensitivity 77.8%, specificity
      93.3%, positive predictive value 63.6%, negative predictive value 96.6%; and
      hysteroscopy revealed sensitivity of 88.9%, specificity 98.3%, positive
      predictive value 88.9%, negative predictive value 98.3%. The combined use of both
      methods revealed sensitivity 100%, specificity 91.7%, positive predictive value
      64.3%, negative predictive value 100%. CONCLUSIONS: Both imagiological methods
      were found to be useful screening tests for endometrial carcinoma. Hysteroscopy
      was a superior diagnostic procedure.

PMID- 11531639
TI  - Cystic degenerated angioleiomyoma mimicking ovarian pathology.

PMID- 11531640
TI  - Ovarian lipoleiomyoma--a rare benign ovarian tumor with pre- and intra-operative
      features suggestive of malignancy.

PMID- 11531641
TI  - Uterine rupture at parturition subsequent to previously repeated cervical
      surgeries.

PMID- 11531643
TI  - A family history can display a synergistic effect of atherogenic and
      prothrombotic risk in pregnancy.

PMID- 11531642
TI  - An unusual cause of hypovolemic shock in the postpartum period.

PMID- 11531645
TI  - In vivo determination of muscle viscoelasticity in the human leg.
AB  - The purpose of this study was to examine the methodological validity of the free
      vibration technique for determining individual viscoelastic characteristics of
      the human triceps surae muscle-tendon complex (MTC) in vivo. Six subjects sat
      with first phalangeal joint of the forefoot on the edge of a force-plate. The
      special frame on the knee was loaded with weight (0-40 kg) for testing.
      Oscillations of the triceps surae MTC system were initiated with a hand-held
      hammer by tapping the weight. In order to keep the same posture, the output of
      the force plate was displayed on the oscilloscope and subjects were asked to
      maintain the beam on the oscilloscope at a particular location in relation to a
      reference line. The damped oscillations in conjunction with the equation of
      motion of a damped mass-spring model were used to calculate the viscosity of
      muscle (b) and the elasticity of muscle fibres and tendon (k) in each subject,
      considering moment arm of the ankle joint. With this arrangement, we have
      obtained high reproducibility in this method. The coefficient of variations (CVs)
      of b and k in five trials at each weight were quite small (range: 0.5-18.7% in b
      and 1.0-15.1% in k). There were no significant differences in viscoelastic
      coefficients between right and left legs. Therefore, it appears that free
      vibration technique, used here, is adequate in describing the viscoelastic
      characteristics of the triceps surae in vivo in humans.

PMID- 11531646
TI  - Muscle volume is a major determinant of joint torque in humans.
AB  - Muscle force (MF) is linearly related to physiological cross-sectional area
      (CSA), which is obtained from muscle volume (MV) divided by fibre length. Taking
      into account the fact that joint torque (TQ) is determined by MF multiplied by
      the moment arm, the maximal TQ would be a function of MV. This proposition was
      tested in the present study by investigating the relationship between MV and TQ
      for elbow flexor (EF) and extensor (EE) muscles of 26 males. The MVs of EF and EE
      were determined from a series of muscle CSA by magnetic resonance imaging (MRI),
      and pennation angle (theta) and FL by ultrasonography (US). Maximal isometric TQ
      was measured at right angle of elbow joint for EF and EE. There was a highly
      significant correlation between MV and TQ both for EF and EE (r=0.95 and 0.96
      respectively) compared with that between muscle CSA and TQ, suggesting the
      dependence of TQ on MV. Furthermore, prediction equations for MV (MVULT) from
      muscle thickness (MT) measured by US was developed with reference to MVMRI by the
      MRI on 26 subjects, and the equations were applied to estimate MV of healthy
      university students (CON; 160 males) and sports athletes (ATH; 99 males). There
      were significant linear relationships between MVULT and TQ both for EF (r=0.783)
      and EE (r=0.695) for all subjects (n=259). The MVULT was significantly higher in
      ATH (by 32% for EF and 33% for EE, respectively) than in CON. Similarly,
      significantly greater TQ was observed in ATH (by 35% for EF, 37% for EE,
      respectively). The theta for EE showed no difference between both groups (17.8
      degrees for CON and 17.5 degrees for ATH). On the other hand, the TQ to MV ratio
      were identical for CON and ATH. The results reveal that the muscle volume of the
      upper arm is a major determinant of joint torque (TQ), regardless of athletic
      training.

PMID- 11531647
TI  - Neural control: novel evaluation of stretch reflex sensitivity.
AB  - We evaluated the stretch reflex activities of the elbow flexor and extensor
      muscles considering the relationship between the reflex electromyographic (EMG)
      responses and their corresponding standardized muscle stretch velocities.
      Specifically, muscular stretch velocity was estimated by using ultrasonograms.
      Stretch reflex EMG responses were elicited in the biceps brachii, brachioradialis
      and triceps brachii with a ramp-and-hold rotation at the elbow joint, which
      consisted of various angular velocities for the extension- or flexion-direction.
      The whole muscle stretch velocity induced by each ramp-and-hold rotation was
      calculated on the basis of fibre length changes associated with the elbow joint
      angle. A linear regression equation was fitted to the relation between the whole
      muscle stretch velocity and the reflex EMG responses, and the variables from the
      equation were used to quantify sensitivity of each reflex EMG component. The
      reflex EMG responses were increased as the ramp-and-hold rotational velocity
      increased. There were no significant differences in the recorded magnitudes of
      reflex EMG responses with equivalent joint rotational velocity between the
      brachioradialis and the triceps brachii medial head. These muscles showed the
      highest reflex responses in the flexor and extensor muscles, respectively. To the
      contrary, the reflex EMG response elicited by the standardized muscle stretches
      was significantly greater in the extensor muscles, indicating a higher reflex
      sensitivity. This was because of the lower muscle stretch velocity of the triceps
      brachii with an equivalent elbow joint rotation. The stretch reflex sensitivity
      in both the elbow flexor and extensor muscles might be regulated so as to make
      the reflex responses the same when the equivalent joint rotational velocity is
      applied to these muscles.

PMID- 11531649
TI  - Force-length characteristics of in vivo human skeletal muscle.
AB  - In the present study, the in vivo force-length relations of the human soleus
      (SOL) and tibialis anterior (TA) muscles were estimated. Measurements were taken
      in six men at ankle angles from 30 degrees of dorsiflexion to 45 degrees of
      plantarflexion in steps of 15 degrees, and involved dynamometry, electrical
      stimulation, ultrasonography and magnetic resonance imaging (MRI). For each
      muscle and ankle angle studied the following three measurements were carried out:
      (1) dynamometry-based measurement of maximal voltage tetanic moment, (2)
      ultrasound-based measurement of pennation angle and fibre length and (3) MRI
      based measurement of tendon moment arm length. Tendon forces were calculated
      dividing moments by moment arm lengths, and muscle forces were calculated
      dividing tendon forces by the cosine of pennation angles. In the transition from
      30 degrees of dorsiflexion to 45 degrees of plantarflexion the SOL muscle fibre
      length decreased from 3.8 to 2.4 cm and its force decreased from 3330 to 290 N.
      Over the same range of ankle angles the TA muscle fibre length increased from 3.7
      to 6 cm and its force increased from 157 to 644 N. Over the longest muscle fibre
      lengths reached the force of both muscles remained approximately constant. These
      results indicate that the intact human SOL and TA muscles operate in the
      ascending limb and plateau region of the force-length relationship. Similar
      conclusions were reached when calculating the theoretical operating range of the
      two muscle sarcomeres in the study.

PMID- 11531648
TI  - Inactivity and muscle: effect of resistance training during bed rest on muscle
      size in the lower limb.
AB  - The present study aimed to investigate the effect of dynamic leg press training
      on the physiological cross-sectional areas (PCSAs) of human lower limb muscles
      during 20 days of 6 degrees head-down tilt bed rest. Five healthy men comprised
      the resistance training group (BR-Tr) and data from two previous studies were
      used to derive a 10-man control group (BR-Cont). The BR-Tr performed two sessions
      (morning and afternoon session) of dynamic leg press action including knee
      extension and plantar flexion daily for the bed rest period: (1) three sets of 10
      repetitions at 90% of maximum load and (2) 40% of maximum load to exhaustion. The
      PCSAs of the knee extensor (KE), knee flexor (KF), plantar flexor (PF), and
      dorsiflexor muscle groups were estimated using serial axial magnetic resonance
      (MR) images of the right-thigh and leg. After the bed rest period, the BR-Tr
      showed a significant increase in the PCSA of the KE. Although PCSA of the KF in
      two groups significantly decreased after bed rest, percentage of change in PCSA
      of the biceps femoris (long head) and semitendinosus muscles in the BR-Tr, which
      occupied approximately 70% of the KF, was significantly higher than those in the
      BR-Cont. Both the BR-Tr and BR-Cont groups showed significant decreases in the
      PCSA of PF with similar magnitude of 11.6% (P < 0.001) and 11.9% (P < 0.001),
      respectively. These results suggest that dynamic leg press training during bed
      rest can prevent deteriorating of the KE and a part of KF, but not the calf
      muscles.

PMID- 11531650
TI  - Prostaglandin E2 concentrations in rat renal cortical and medullary interstitium:
      effect of volume expansion and renal perfusion pressure.

PMID- 11531651
TI  - The role of neuronal nitric oxide synthase in ischaemia-reperfusion injury of the
      isolated mouse heart.

PMID- 11531652
TI  - Can lithium help to prevent suicide?

PMID- 11531653
TI  - Lower suicide risk with long-term lithium treatment in major affective illness: a
      meta-analysis.
AB  - OBJECTIVE: To compare suicide rates with vs. without long-term lithium treatment
      in major affective disorders. METHOD: Broad searching yielded 22 studies
      providing suicide rates during lithium maintenance; 13 also provide rates without
      such treatment. Study quality was scored, between-study variance tested, and
      suicide rates on vs. off lithium examined by meta-analyses using random-effects
      regression methods to model risk ratios. RESULTS: Among 5647 patients (33 473
      patient-years of risk) in 22 studies, suicide was 82% less frequent during
      lithium-treatment (0.159 vs. 0.875 deaths/100 patient-years). The computed risk
      ratio in studies with rates on/off lithium was 8.85 (95% CI, 4.12-19.1;
      P<0.0001). Higher rates off-lithium were not accounted for by treatment
      discontinuation. CONCLUSION: Suicide risk was consistently lower during long-term
      treatment of major affective illnesses with lithium in all studies in the meta
      analysis, including the few involving treatment-randomization.

PMID- 11531654
TI  - CYP2D6 and CYP2C19 genotype-based dose recommendations for antidepressants: a
      first step towards subpopulation-specific dosages.
AB  - OBJECTIVE: This review aimed to provide distinct dose recommendations for
      antidepressants based on the genotypes of cytochrome P450 enzymes CYP2D6 and
      CYP2C19. This approach may be a useful complementation to clinical monitoring and
      therapeutic drug monitoring. METHOD: Our literature search covered 32
      antidepressants marketed in Europe, Canada, and the United States. We evaluated
      studies which had compared pharmacokinetic parameters of antidepressants among
      poor, intermediate, extensive and ultrarapid metabolizers. RESULTS: For 14
      antidepressants, distinct dose recommendations for extensive, intermediate and
      poor metabolizers of either CYP2D6 or CYP2C19 were given. For the tricyclic
      antidepressants, dose reductions around 50% were generally recommended for poor
      metabolizers of substrates of CYP2D6 or CYP2C19, whereas differences were smaller
      for the selective serotonin reuptake inhibitors. CONCLUSION: We have provided
      preliminary average dose suggestions based on the phenotype or genotype. This is
      a first attempt to apply the new pharmacogenetics to suggest dose-regimens that
      take the differences in drug metabolic capacity into account.

PMID- 11531655
TI  - Lithium and suicidal behavior in major affective disorder: a case-control study.
AB  - OBJECTIVE: A number of studies have suggested that lithium may be particularly
      effective in reducing suicide risks among patients with major affective
      disorders. The design of many of these studies left them open to biases
      associated with treatment compliance, however. METHOD: Subjects were drawn from a
      naturalistic, long-term follow-up of patients with major affective disorders.
      Fifteen who committed suicide while receiving somatotherapy where matched to non
      suicidal patients who were similarly receiving somatotherapy at the same point in
      follow-up. The same procedure was followed for 41 patients who made a serious
      suicide attempt during follow-up. RESULTS: Six (40.0%) of the patients who
      committed suicide, and eight (53.3%) of their controls, were thought to have been
      taking lithium in the preceding week. Among attempters and their controls, nine
      (22.0%) and eight (19.5%), respectively, were taking lithium. CONCLUSION: These
      results do not support previous suggestions that lithium has uniquely
      antisuicidal properties. Other existing datasets should be explored with this
      design to establish whether lithium does, or does not, offer special protection
      against suicide.

PMID- 11531656
TI  - Suicidal behaviour and family factors among Dutch and Slovenian high school
      students: a comparison.
AB  - OBJECTIVE: East European countries have much higher suicide rates than West
      European countries. Whether this also applies for suicidal ideation and suicide
      attempts is not known. In addition, the role of family factors in relation to
      suicidal behaviour has not been investigated in East European countries. METHOD:
      Two representative samples of 19,250 Dutch and 4706 Slovenian high school
      students were compared on the basis of self-report data. RESULTS: Slovenian
      students report more suicidal behaviour (ideation and attempts) as well as more
      unfavourable family circumstances than Dutch students. This applies especially to
      the death of parent(s), the number of changes in their living situation, and to
      conflicts between or with parents. CONCLUSION: A relation between family
      characteristics and suicidal behaviour is established in both samples, but proved
      to be strongest in Slovenian girls. Complicated cultural and socioeconomic
      differences between the two countries may account for the reported differences.

PMID- 11531657
TI  - The validity of proxy-based data in suicide research: a study of patients 50
      years of age and older who attempted suicide. I. Psychiatric diagnoses.
AB  - OBJECTIVE: To investigate the validity of best-estimate methodology for making
      psychiatric diagnoses among individuals who attempted suicide. METHOD: Subjects
      were 80 patients admitted for treatment following a suicide attempt. Psychiatric
      diagnoses based on structured interviews with subjects were compared with
      diagnoses made based on interviews with proxy respondents. In both cases,
      interview information was supplemented with pre-admission psychiatric and medical
      records to inform diagnoses. RESULTS: Diagnostic agreement, based on kappa
      coefficients, was substantial for major depression and bipolar disorders, and
      moderate for non-affective psychoses, organic mood and anxiety disorders.
      Agreement was substantial for substance dependence but poor for substance abuse
      disorders. CONCLUSION: Results support best-estimate methodology for making mood
      and substance dependence diagnoses in research of suicidal behavior in this age
      group, with potential implications for interpreting postmortem research of
      completed suicide.

PMID- 11531658
TI  - Depression in relation to age and gender in the general population: the Nord
      Trondelag Health Study (HUNT).
AB  - OBJECTIVE: Previous sample studies of depression have shown a higher prevalence
      of depression in women, and an inconsistent relation to age has been found for
      both genders. The aim of the present study was to investigate depression in
      relation to gender and age in the general adult population. METHOD: Of the total
      population of 92,100 individuals aged 20-89 years and living in Nord-Trondelag
      county of Norway, 62,344 (67.7%) filled in valid ratings of depression on the
      Hospital Anxiety and Depression Scale (HADS). RESULTS: Minimal gender difference
      was found in dimensional depression scores and in prevalence rates of depression.
      Both these measures were found to increase continuously with age in both genders.
      CONCLUSION: Our results of this population-based study differ from most sample
      studies reported, and these discrepancies are discussed with focus on study
      design, self-rating, and the concept of depression covered by HADS.

PMID- 11531659
TI  - Sociopsychiatric characteristics of adolescents who use computers to excess.
AB  - OBJECTIVE: This study attempted to investigate current computer use by Korean
      adolescents, consequences of its excessive use and its relationship to
      psychiatric symptoms. METHOD: Questions for computer use, Computer-Related
      Addictive Behavior Inventory (CRABI), computer-induced behavioral alterations and
      Symptom Checklist-90-Revision (SCL-90-R) were assessed in 1296 students (12-19
      years). RESULTS: Students were divided into three group users: minimal users
      (63.4%), moderate users (30.5%) and excessive users (6.1%). Computer-induced
      behavioral alterations occurred most frequently to excessive users and it was
      significantly correlated with total CRABI score. Average score on nine symptom
      dimensions and three global indexes of SCL-90-R were able to discriminate four
      decreasing orders of subjective psychiatric complaints: most frequent in
      excessive users and then moderate, non- and mild users, in order. CONCLUSION:
      Those adolescents with excessive computer use were found to show serious
      sociopsychiatric problems.

PMID- 11531660
TI  - Telepsychiatry: assessment of televideo psychiatric interview reliability with
      present- and next-generation internet infrastructures.
AB  - OBJECTIVE: We assessed the reliability of remote video psychiatric interviews
      conducted via the internet using narrow and broad bandwidths. METHOD: Televideo
      psychiatric interviews conducted with 42 in-patients with chronic schizophrenia
      using two bandwidths (narrow, 128 kilobits/s; broad, 2 megabits/s) were assessed
      in terms of agreement with face-to-face interviews in a test-retest fashion. As a
      control, agreement was assessed between face-to-face interviews. Psychiatric
      symptoms were rated using the Oxford version of the Brief Psychiatric Rating
      Scale (BPRS), and agreement between interviews was estimated as the intraclass
      correlation coefficient (ICC). RESULTS: The ICC was significantly lower in the
      narrow bandwidth than in the broad bandwidth and the control for both positive
      symptoms score and total score. CONCLUSION: While reliability of televideo
      psychiatric interviews is insufficient using the present narrow-band internet
      infrastructure, the next generation of infrastructure (broad-band) may permit
      reliable diagnostic interviews.

PMID- 11531661
TI  - Dysfunction of transcallosally mediated motor inhibition and callosal morphology
      in patients with schizophrenia.
AB  - OBJECTIVE: In order to assess the functional integrity of motor pathways through
      the corpus callosum (CC) in patients with schizophrenia transcallosally mediated
      inhibition (TI) of voluntary tonic EMG activity of first dorsal interosseus
      muscle following ipsilateral focal transcranial magnetic stimulation (fTMS) was
      investigated. In addition thickness and length of CC were calculated. METHOD:
      Twelve patients suffering from schizophrenia and 12 healthy controls were
      investigated. CC morphology was measured in mid-sagittal MRI-slices. Latency and
      duration of TI were calculated. RESULTS: In schizophrenics the duration of TI was
      significantly prolonged, whereas latencies were not. In addition, a lack of TI
      was found unilaterally in three patients. Measurements of CC revealed a
      significantly reduction of the length and thickness in the anterior part of CC in
      patients. CONCLUSION: These findings indicate that measurement of TI could be
      used to detect clinical silent affection of transcallosal motor pathways in
      schizophrenics. The effect of neuroleptic drugs has to be explored.

PMID- 11531662
TI  - Dose-response relationship of selective serotonin reuptake inhibitors treatment
      emergent hypomania in depressive disorders.
AB  - OBJECTIVE: The notion that antidepressant treatment-associated hypomania or mania
      being pharmacologically induced has been challenged. To determine whether
      selective serotonin reuptake inhibitors (SSRI) induced hypomania is secondary to
      medication effects, we examined the dose-response relationship of SSRI-induced
      hypomania in two patients with depressive disorder. METHOD: Case study. RESULT:
      Hypomanic symptoms emerged during treatment with sertraline at the dose of 300 mg
      per day in a 45-year-old male with major depression. Paroxetine treatment at the
      dose of 80 mg per day induced hypomania in a 37-year-old female with dysthymia
      and trichitillomania. These patients have no family or personal history of
      bipolar disorder. Hypomania resolved when sertraline was decreased to 200 mg per
      day and paroxetine to 40 mg per day. No hypomanic switch was observed during 18
      24 months follow-up. CONCLUSION: In the absence of risk factors for manic switch,
      SSRI-induced hypomania may be dose-dependent medication effects.

PMID- 11531664
TI  - Safety matters.

PMID- 11531665
TI  - Airway obstruction with cricoid pressure and lateral tilt.
AB  - We studied the effect of cricoid pressure and lateral tilt on airway patency
      during ventilation by facemask in a simulated obstetric setting. The lungs of 50
      patients were ventilated by facemask and Guedel airway using a Nuffield Penlon
      200 ventilator and Bain system with standard settings. Expired tidal volumes and
      peak inspiratory pressures were recorded for 10 breaths in each of four
      combinations: supine with no cricoid pressure, supine with cricoid pressure, 15
      degrees lateral tilt with no cricoid pressure and 15 degrees lateral tilt with
      cricoid pressure. The timing of cricoid pressure was randomised and blinded to
      all observers. In both supine and tilted positions, cricoid pressure produced a
      reduction in tidal volume (p < 0.001) and an increase in peak inspiratory
      pressure (p < 0.001). Cricoid pressure with lateral tilt did not produce any
      additional airway obstruction to that in the supine position. Complete airway
      obstruction (tidal volume < 200 ml) resulted on three occasions, all with cricoid
      pressure applied.

PMID- 11531666
TI  - Exploration of xenon as a potential cardiostable sedative: a comparison with
      propofol after cardiac surgery.
AB  - Xenon anaesthesia is thought to have minimal haemodynamic side-effects. It is,
      however, expensive and requires special delivery systems for economic use. In
      this randomised cross-over study, we: (i) investigated the haemodynamic profile
      and recovery characteristics of xenon compared with propofol sedation in
      postoperative cardiac surgery patients, and (ii) evaluated a fully closed
      breathing system to minimise xenon consumption. We demonstrated a significantly
      faster recovery from xenon (3 min 11 s) than propofol sedation (25 min 23 s).
      Relative to propofol, xenon sedation produced no change in heart rate or mean
      arterial pressure and there were significantly higher mean values for central
      venous pressure (10.6 vs. 8.9 mmHg), pulmonary artery occlusion pressure (11.2
      vs. 9.5 mmHg), mean pulmonary artery pressure (20.1 vs. 18.3 mmHg) and systemic
      vascular resistance index (2170 vs. 1896 dyn.s.cm-5.m-2). The haemodynamic
      profile seen with propofol reflected its known vasodilator effects. This was
      supported by the almost identical left ventricular stroke work indexes seen with
      both methods of sedation.

PMID- 11531668
TI  - Intermediate outcome of medical patients after intensive care.
AB  - Medical patients suffer a high mortality after critical illness; however, the
      causes of mortality after intensive care management are unclear. This study's
      aims were to (a) explore what factors affect outcome after intensive care and (b)
      identify medical patients at particularly high risk of mortality. During one
      year, all patients admitted with a medical cause to the Critical Care Complex
      were enrolled. Diagnosis on admission was recorded, and whether the reason for
      admission was a new clinical problem or an exacerbation of existing chronic
      illness. All patients were followed for a minimum of one year. A total of 186
      medical patients were included in the study. Fifty-four medical patients died on
      intensive care (28.4% mortality), a further 16 died on the general ward after
      intensive care unit discharge (hospital mortality 36.8%) and six following
      discharge home (1 year's mortality 40.9%). Of the 16 patients who died on the
      general ward, 12 had been admitted to the intensive care unit with a new,
      previously unrecognised problem rather than exacerbation of a chronic pre
      existing problem. However, on the general ward, 'Do Not Resuscitate' orders were
      placed on seven of these 12 patients. It would appear that some of the high post
      intensive care hospital mortality might be due to changes in resuscitation status
      in patients expected to survive following intensive care unit discharge.

PMID- 11531667
TI  - Effects of postoperative sedation with propofol and midazolam on pancreatic
      function assessed by pancreatitis-associated protein.
AB  - This prospective randomised controlled study evaluated the effects of
      postoperative sedation with propofol and midazolam on pancreatic function. We
      studied 42 intensive care unit patients undergoing elective major surgery who
      were expected to be sedated postoperatively. Patients were randomly assigned to a
      propofol group (n = 21) or a midazolam group (n = 21). To assess pancreatic
      function, the following parameters were measured: pancreatitis-associated
      protein, amylase, lipase, cholesterol and triglyceride prior to start of sedation
      on the intensive care unit, 4 h after the sedation was started and at the first
      postoperative day. Patients in the propofol group received on average (SD) 1292
      (430) mg propofol and were sedated for 9.03 (4.26) h. The midazolam group
      received 92 (36) mg midazolam and were sedated for 8.81 (4.68) h. Plasma
      cholesterol concentrations did not differ significantly between groups.
      Triglyceride plasma levels 4 h after the start of infusion were significantly
      higher in the propofol group (140 (54) mg.dl(-1)) than the midazolam-treated
      patients (81 (29) mg.dl(-1)), but were within normal limits. There were no
      significant differences between the two groups regarding amylase, lipase and
      pancreatitis-associated protein plasma concentrations at any time. No markers of
      pancreatic dysfunction were outside the normal range. We conclude that
      postoperative sedation with propofol induced a significant increase of serum
      triglyceride levels but that pancreatic function is unchanged with standard doses
      of propofol.

PMID- 11531669
TI  - Blood pressure measurement in volunteers with and without padding between the
      cuff and the skin.
AB  - Automated non-invasive arterial blood pressure measurements are made frequently
      during anaesthesia. Conscious patients often find the measurement uncomfortable.
      The tissues under the cuff can suffer trauma such as skin creasing, blistering,
      petechial haemorrhages and even nerve damage. We placed soft padding between the
      blood pressure measurement cuff and the skin of the upper arm of 140 healthy
      volunteers, and compared cuff-related skin trauma and arterial blood pressure
      measurements with and without the padding. Padding was associated with a
      significant reduction in the frequency and intensity of skin trauma (p < 0.0001).
      There was no significant overall effect of the presence of padding on arterial
      blood pressure readings. We conclude that the benefit of padding outweighs any
      compromise to the reliability of arterial blood pressure measurement.

PMID- 11531670
TI  - Sequential organ scoring as a measure of effectiveness of care in the high
      dependency unit.
AB  - High-dependency units are of benefit to patients and to the associated intensive
      care unit. However, the effectiveness of high-dependency care has not been
      quantified. We studied 100 consecutive patients whose high-dependency unit
      admission was longer than 48 h. The Logistic Organ Dysfunction System was used to
      assess organ dysfunction on a daily basis in these patients. The median Logistic
      Organ Dysfunction System score on admission was 3. The mean duration of stay was
      4.3 days, and the median Logistic Organ Dysfunction System score on day 4 was 1.
      Sixty-six per cent of patients had a lower Logistic Organ Dysfunction System
      score at discharge. In the remaining patients, the commonest reason for no change
      or a higher Logistic Organ Dysfunction System score was renal dysfunction. High
      dependency care is effective in the majority of patients in terms of improved
      physiological status and most patients were discharged with minor physiological
      dysfunction. This level of physiological dysfunction could be applied as a
      discharge threshold. Poorer patient outcome is associated with increased age and
      a longer stay on the unit. This poor outcome was commonly due to renal system
      dysfunction, and invariably followed surgery.

PMID- 11531671
TI  - Maternal anti-factor Xa activity following subcutaneous unfractionated heparin
      after Caesarean section.
AB  - Unfractionated heparin is widely used for prophylaxis against venous
      thromboembolism after Caesarean section. We performed a survey of
      thromboprophylactic methods after elective Caesarean section in 50 maternity
      units in the United Kingdom. We found that a variety of regimens were used.
      Thirteen (26%) used subcutaneous unfractionated heparin at standard (non
      pregnant) doses. We then studied anti-Xa activity in women following elective
      Caesarean section under regional anaesthesia. Initially, eight women were given
      5000 U unfractionated heparin subcutaneously after surgery and anti-Xa activity
      was measured 1, 2, 3, 4, 5, 6, 8 and 10 h after administration. There was no
      detectable anti-Xa activity in any of the samples so the dose was increased to
      7500 U in a further five women and a single anti-Xa assay performed at 3 h when
      peak activity should occur. Again, no activity was detected so the dose was
      increased to 10 000 U heparin in a final group of 10 women and anti-Xa activity
      measured at 0.5, 1, 1.5, 2, 3, 4, 5 and 6 h. Although there was some activity
      after 10 000 U heparin, the level was below that accepted for prophylaxis. If
      anti-Xa activity is an appropriate monitor of prophylactic unfractionated
      heparin, doses up to 10 000 U are inadequate. Since there is evidence that
      enoxaparin is effective at producing adequate prophylactic anti-Xa activity
      following Caesarean section, we suggest abandoning the use of unfractionated
      heparin in favour of enoxaparin for this purpose.

PMID- 11531672
TI  - Evaluation of a new percutaneous dilatational tracheostomy set apparatus.
AB  - Percutaneous tracheostomy is a well established technique used primarily to
      assist weaning from mechanical ventilation on many intensive care units. We
      report our experiences of a total of 36 procedures performed with the new Blue
      Rhino Percutaneous Tracheostomy Introducer Set developed by Ciaglia. The
      technique was successful in all cases and was simpler and quicker to perform than
      with the earlier Ciaglia percutaneous tracheostomy set. Difficulties were
      encountered when using Shiley tracheostomy tubes. Significant complications
      included one posterior wall tear and one tracheal cartilage ring fracture.

PMID- 11531673
TI  - The effect of the Lockit epidural catheter clamp on epidural migration: a
      controlled trial.
AB  - We investigated the efficacy of using the Lockit epidural catheter clamp in
      preventing epidural catheter migration in patients receiving postoperative
      analgesia via an epidural infusion after major surgery. Patients were randomly
      allocated to receive either a standard epidural dressing, a coiled catheter with
      transparent adhesive dressing and tape (n = 54), or the Lockit epidural catheter
      clamp (n = 48). There was no movement from the insertion position in 88% of the
      Lockit group compared with only 28% in the standard group (p < 0.001). Outward
      migration of > 2 cm occurred in 26% of the standard group compared with just 6%
      of the Lockit group (p < 0.01). Inward migration of > 1 cm occurred in 17% of the
      standard group but in none of the Lockit group (p < 0.01). Catheter migration was
      assessed as being the cause of analgesic failure in 15% of the standard group but
      in only 4% of the Lockit group (p < 0.05). We conclude that the Lockit epidural
      catheter clamp significantly reduces catheter migration in a safe and non
      invasive fashion.

PMID- 11531675
TI  - A Staphylococcus aureus paraspinal abscess associated with epidural analgesia in
      labour.
AB  - A case is described in which a parturient developed a Staphylococcus aureus
      paraspinal abscess following epidural analgesia in labour. We compared this case
      with other reported cases of paraspinal abscesses in obstetric patients. The
      presentation, diagnosis and management of these cases were reviewed.
      Anaesthetists need to be aware that non-spinal-epidural abscesses can occur in
      patients with an associated labour epidural.

PMID- 11531676
TI  - Information and consent for anaesthesia: a postal survey of current practice in
      Great Britain.
AB  - A postal questionnaire survey was sent to Royal College of Anaesthetists' tutors
      in Great Britain and Northern Ireland to gain insight into current practice with
      regard to information and consent for anaesthesia. Details of consent practice in
      three specific areas were requested: anaesthesia in general, teaching medical
      students during anaesthesia and obstetric anaesthesia. Replies were received from
      218 tutors (77%). Of these, 72% of departments had a policy on consent for
      anaesthesia that was in accordance with The Association of Anaesthetists of Great
      Britain and Ireland guidelines on 'Information and Consent for Anaesthesia'. We
      identified three areas of concern. Firstly, almost a third of departments (27%)
      had no policy on consent for anaesthesia. Second, only 18% of relevant
      departments obtain specific consent for the teaching of medical students on
      anaesthetised patients. Third, 1 year after publication of the guidelines, 17% of
      obstetric anaesthetic units, despite stating an intention to alter their
      departmental policy based on the Association's recommendations, had not yet
      implemented any changes.

PMID- 11531677
TI  - Medical repatriation via fixed-wing air ambulance: a review of patient
      characteristics and adverse events.
AB  - Anaesthetists are often employed as medical escorts for patients undergoing
      international transfer by air ambulance. There is little published data on the
      types of patients being transferred and on the incidence of adverse events. We
      performed a retrospective review of the documentation of all air ambulance
      transfers performed by a single company over a 2-year period followed by a
      prospective assessment of all high-risk patients transferred over a 1-year
      period. Of 483 transfers identified, 47% were defined as high-risk and 20% were
      of patients receiving mechanical ventilation. In the prospective group, 28% of
      patients required pretransfer optimisation, 7% required a major therapeutic
      intervention during transfer and there was a major adverse event in 12% of
      transfers. There were two deaths during transport. These data support the
      recommendation that escorting personnel should be from an appropriate speciality,
      have reasonable seniority and be adequately trained and supervised.

PMID- 11531678
TI  - A study of bispectral analysis and auditory evoked potential indices during
      propofol-induced hypnosis in volunteers: the effect of an episode of wakefulness
      on explicit and implicit memory.
AB  - The bispectral index (BIS) and the auditory evoked potential (AEP) index as
      calculated by the new A-line monitor were measured during hypnosis with propofol,
      which included an episode of wakefulness. Both indices followed a similar pattern
      during sedation, with values decreasing with sedation and increasing when awake.
      Baseline AEP values varied between 60 and 98, and BIS values were between 96 and
      98. The AEP-index value was at all times 10-20 points lower than the BIS-index.
      The transition to loss of response occurred at a mean AEP value of 46 and BIS
      value of 58. The transition to just responding following a period of
      unconsciousness occurred at a mean AEP value of 46 and BIS 65. Both monitoring
      techniques, however, displayed large interindividual variations making it
      impossible to discriminate in real time between subtle changes of clinical state.
      The new neurophysiological monitors A-line AEP and BIS are interesting tools for
      creating a better understanding of the anaesthetic effects of drugs; however,
      further refinements are required before their relative roles can be fully
      established in the clinical setting.

PMID- 11531679
TI  - The effect of prophylactic metaraminol on systemic hypotension caused by
      induction of anaesthesia with propofol in patients over 55 years old.
AB  - We conducted a double-blind, randomised, placebo-controlled study evaluating the
      efficacy of prophylactic metaraminol for preventing propofol-induced hypotension.
      Thirty patients aged 55-75 years undergoing general anaesthesia were randomly
      allocated to receive either metaraminol 0.5 mg or saline before administration of
      fentanyl 1 microg.kg(-1) and propofol 2 mg.kg(-1). Induction of anaesthesia was
      associated with a decrease in mean and systolic arterial pressure in both groups
      (p = 0.0001). However, there was no significant difference between the two
      groups. These results show that prophylactic use of metaraminol 0.5 mg does not
      prevent the decrease in blood pressure following fentanyl and propofol induction
      in older patients.

PMID- 11531680
TI  - Facilitation of laryngeal mask airway insertion: effects of remifentanil
      administered before induction with target-controlled propofol infusion.
AB  - Eighty-six adult day-case patients were recruited into a prospective, randomised
      study and allocated to one of two groups. Patients received either intravenous
      remifentanil 0.3 microg.kg(-1) or an equivalent volume of sodium chloride 0.9%
      followed by induction of anaesthesia with propofol target-controlled infusion
      until the effect (brain) site calculated concentration was 2 microg.ml(-1). Jaw
      opening and ease of laryngeal mask insertion were assessed immediately after mask
      insertion. A higher incidence of failure of induction of anaesthesia was observed
      in the control group compared with the remifentanil group [15 (35%) vs. 3 (7%); p
      < 0.01] and addition of remifentanil significantly increased the ease and success
      of laryngeal mask insertion, with grade 1 (no coughing/gagging) conditions
      observed in 29 (68%) of the remifentanil group and 21 (49%) of the control group
      (p < 0.01). The doses of remifentanil and propofol used were not associated with
      any significant cardiorespiratory instability. In conclusion, when combined with
      propofol target-controlled infusion, remifentanil 0.3 microg.kg(-1) facilitates
      laryngeal mask insertion with minimal adverse haemodynamic changes.

PMID- 11531681
TI  - Effect of ondansetron pretreatment on pain after rocuronium and propofol
      injection: a randomised, double-blind controlled comparison with lidocaine.
AB  - In a randomised, controlled, double-blinded trial to study the effect of
      ondansetron pretreatment on the pain produced after intravenous injection of
      rocuronium and propofol in comparison with lidocaine, 60 patients were randomly
      assigned to one of three groups. Group 1 received 5 ml of intravenous 0.9% sodium
      chloride solution pretreatment, group 2 received ondansetron 4 mg (2 mg.ml-1
      solution) diluted into a 5-ml solution, and group 3 received 50 mg lidocaine (5
      ml 1% solution); this was followed 1 min later by rocuronium and propofol. Pain
      was reduced significantly in the ondansetron and lidocaine groups (p < 0.0001)
      compared with placebo, and significantly better with lidocaine than with
      ondansetron (p = 0.02). We conclude that ondansetron is effective in relieving
      the pain of rocuronium but is not as effective as lidocaine.

PMID- 11531682
TI  - Patient consent for case reports.

PMID- 11531683
TI  - The fresh-gas flow sequence at the start of low-flow anaesthesia.

PMID- 11531684
TI  - Pressure exerted by the cuff of the laryngeal tube on the oropharynx.

PMID- 11531685
TI  - Tonsillectomy--anaesthetic technique and the new disposable surgical equipment.

PMID- 11531686
TI  - Potential hazard with syringe infusion pump.

PMID- 11531687
TI  - Incorrect assembly of the flexiblade fibreoptic bundle.

PMID- 11531689
TI  - The importance of a Murphy Eye.

PMID- 11531690
TI  - Survey of cricoid pressure application by anaesthetists, operating department
      practitioners, intensive care and accident and emergency nurses.

PMID- 11531691
TI  - Misidentification, in-filling and confirmation bias.

PMID- 11531692
TI  - Vascular access procedures for haemodialysis--potential hazard of regional
      anaesthesia.

PMID- 11531694
TI  - Do anaesthetists benefit from general medical experience?

PMID- 11531695
TI  - Transcriptome of channel catfish (Ictalurus punctatus): initial analysis of genes
      and expression profiles of the head kidney.
AB  - Analysis of expressed sequence tags (ESTs) is an efficient approach for gene
      discovery, expression profiling, and development of resources useful for
      functional genomics studies. As part of the transcriptome analysis in channel
      catfish (Ictalurus punctatus), we have conducted EST analysis using a cDNA
      library made from the head kidney. We analysed 2228 EST clones. Orthologues were
      established for 1495 (67.1%) clones representing 748 genes, of which 545 (36.5%)
      clones were singletons. The remaining 733 (32.9%) clones represent unknown gene
      clones, for which the number of genes has not yet been determined.

PMID- 11531696
TI  - Bovine melanocortin receptor 4: cDNA sequence, polymorphisms and mapping.
AB  - A cDNA encoding the bovine melanocortin receptor 4 (MC4R) was cloned and
      sequenced. Comparing human, pig and rat homologues showed a 87, 85 and 89%
      identity on the DNA level, respectively, and over 90% on the protein level. The
      bovine MC4R gene was mapped to BTU 24 by radiation hybrid mapping. Two nucleotide
      changes were identified by single stranded conformation polymorphism (SSCP) and
      sequencing. The substitutions proved to be a T to C and G (allele B) to A (allele
      A) resulting, respectively, in a conservative valine to alanine substitution (Val
      145 Ala) and an alanine to threonine (Ala 172 Thr). Using PCR-RFLP, 13 different
      cattle breeds were screened for the presence of the Ala 172 Thr substitution.
      With the exception of one Red Pied animal, allele A could only be detected in Red
      Holstein animals.

PMID- 11531697
TI  - Nomenclature for factors of the dog major histocompatibility system (DLA), 2000:
      second report of the ISAG DLA Nomenclature Committee.
AB  - The International Society for Animal Genetics (ISAG) Dog Leukocyte Antigen (DLA)
      Nomenclature Committee met during the "Comparative Evolution of the Mammalian
      major Histocompatibility Complex (MHC)" meeting in Manchester, UK on 10 September
      2000. The main points discussed were the naming of class I genes and alleles, and
      the inclusion of alleles from other canidae.

PMID- 11531698
TI  - Construction and characterization of BAC libraries for three fish species;
      rainbow trout, carp and tilapia.
AB  - Bacterial artificial chromosome (BAC) libraries are important tools for genomic
      research. We have constructed seven genomic BAC libraries from three fish
      species, rainbow trout (Oncorhynchus mykiss), carp (Cyprinus carpio) and tilapia
      (Oreochromis niloticus). The two rainbow trout BAC libraries have average insert
      sizes of 58 and 110 kb. The average size of inserts in the carp BAC library is
      160 kb. The average insert sizes of the four tilapia BAC libraries are 65, 105,
      145 and 194 kb, respectively. These libraries represent good coverage of each
      genome (2-64 x coverage). The libraries can be screened by conventional colony
      hybridization and provide a starting point for the construction of high-density
      filtres or polymerase chain reaction (PCR) screening approaches. These BAC
      libraries will facilitate the positional cloning of quantitative trait loci
      (QTLs) for a variety of economically important traits in these species.

PMID- 11531699
TI  - Radiation hybrid comparative mapping between human chromosome 17 and porcine
      chromosome 12 demonstrates conservation of gene order.
AB  - A comparative study of human chromosome 17 (HSA17) and pig chromosome 12 (SSC12)
      was conducted using both somatic cell hybrid panel (SCHP) and radiation hybrid
      (RH) panel analysis. Sequences from an expressed sequence tag (EST) project in
      pig reproduction were examined and six genes and ESTs originally believed to map
      to HSA17 were selected for this study. The genes/ESTs were TATA box binding
      protein-associated factor (TAF2N/RBP56), alpha-2-plasmin inhibitor
      (SERPINF2/PLI), H3 histone family 3B (H3F3B), aminopeptidase puromycin sensitive
      (NPEPPS), an expressed sequence tag (ESTMI015) and P311 protein (P311). The SCHP
      analysis mapped five genes/ESTs (TAF2N, H3F3B, SERPINF2, NPEPPS and ESTMI015) to
      SSC12q11-q15 and SSC12p11-p15 with 100% concordance, and assigned P311 to SSC2
      (1/2q24)-q29 with 100% concordance. Radiation hybrid analysis of all six genes
      confirmed the SCHP mapping results, with average retention frequency of 25%.
      Recent human sequence data demonstrated that P311 is actually located on HSA5q.
      As HSA5q and SSC2q show conserved syntenic regions predicted from bi-directional
      painting, our P311 mapping data is consistent with these results. An expanded
      comparative SSC12 RH map integrating the five new type I markers and 23
      previously mapped loci was established using a LOD score threshold of 4.8. The
      gene order of the five genes/ESTs on the SSC12 framework RH map (H3F3B-ESTMI015
      NPEPPS-TAF2N-SERPINF2) is identical to the HSA17 GB4 map but with inversion of
      the map as conventionally drawn.

PMID- 11531700
TI  - A genetic analysis of the London strain of rainbow trout.
AB  - The London strain of rainbow trout (Oncorhynchus mykiss) was created by
      interbreeding three other strains of rainbow trout and therefore was expected to
      have higher levels of genetic variation than other strains of rainbow trout. We
      examined 129 London strain rainbow trout from Indiana by allozyme electrophoresis
      to assess levels of genetic variation and to examine the relationship between the
      London strain and other hatchery strains. When using the same loci to compare
      with other hatchery strains the London strain showed levels of genetic variation
      within the range of other hatchery strains: mean heterozygosity of 0.053 (0.031
      0.099), 1.27 (1.20-1.60) alleles per locus and 20.0% (20.0-40.0%) of the loci
      were polymorphic. The London strain is somewhat distinct from other hatchery
      strains (D=0.009-0.072), in part because of the high frequency of the sIDHP*40
      allele.

PMID- 11531701
TI  - Characterization of swine leptin (LEP) polymorphisms and their association with
      production traits.
AB  - Four polymorphisms in the swine leptin (LEP) gene were characterized and
      evaluated for association with economically important production traits in
      Yorkshire, Landrace and Duroc pigs. Our results show that these polymorphisms are
      generally of low frequency or are absent in pig populations. Two polymorphisms
      (A2845T and T3469C) may be associated (P < 0.0078) with feed intake and growth
      rate traits in Landrace pigs.

PMID- 11531702
TI  - Multi-primer target PCR for rapid identification of bovine DRB3 alleles.
AB  - Multi-primer target polymerase chain reaction (MPT-PCR) is a rapid method for the
      identification of specific BoLA-DRB3 alleles. In a single PCR reaction, the
      presence of two alleles associated with increased risk, DRB3.2*23 (DRB3*2701
      2703, 2705-2707) and decreased risk, DRB3.2*16 (DRB3*1501, 1502), of mastitis in
      Canadian Holstein can be detected. Two outer primers amplify exon 2 of DRB3.
      Simultaneously, two inner, allele-specific primers amplify individual alleles.
      Initially, 40 cows previously typed by PCR-restriction fragment length
      polymorphism (PCR-RFLP) were genotyped using the multi-primer approach. An
      additional 30 cows were first genotyped by multi-primer target PCR, then by PCR
      RFLP. All animals were correctly identified and there were no false positives.
      This technique can readily be modified to identify other BoLA alleles of
      interest.

PMID- 11531703
TI  - Polymorphic microsatellites developed by cross-species amplifications in common
      pheasant breeds.
AB  - Genetic variability was analysed in two common breeds of pheasant (Phasianus
      colchicus L. 1758) by means of cross-species amplifications of microsatellite
      loci: 154 chicken, Gallus gallus and 32 turkey, Meleagris gallopavo, primers were
      tested for amplification of pheasant DNA. Thirty-six primers (25 specific for
      chicken and 11 for turkey) amplified pheasant DNA. Fifteen markers yielded
      specific products and were tested for polymorphism. Eight of them (55%) were
      polymorphic, with an average polymorphism of two alleles per locus. Specific
      polymerase chain reaction (PCR) products were sequenced; repeats were found in 11
      of the 15 markers, although only two loci showed the same repeat and could be
      homologous to chicken ones.

PMID- 11531704
TI  - Genetic polymorphism of goat kappa-casein (CSN3) in different breeds and
      characterization at DNA level.
AB  - Data on genetic differences at CSN3 in goat breeds including a DNA based typing
      method and the mutations responsible for variation on protein and DNA level are
      presented here. Isoelectric focusing (IEF) in ultrathin polyacrylamide gels with
      carrier ampholytes was used to demonstrate CSN3 polymorphism in milk samples of
      Italian (Orobica n=88; Ionica n=68) and German goat breeds (Bunte Deutsche
      Edelziege n=244; Weisse Deutsche Edelziege n=134; Toggenburger n=25; Thuringer
      Waldziege n=70). A further CSN3 band was found presenting a more cathodic
      migration than CSN A. After chymosin action, the genetic polymorphism was also
      observed in the para-kappa-casein fraction. The new allele CSN3(B) was spread
      mainly in Orobica (37%), Bunte Deutsche Edelziege (11%) and Ionica (10%). CSN3(B)
      occurred in low frequency (<3%) in Thuringer Waldziege and in Weisse Deutsche
      Edelziege, and could not be demonstrated in milk samples of Toggenburger. The
      populations were in Hardy-Weinberg equilibrium at CSN3. The codominant genetic
      control of CSN3(B) was confirmed by genetic studies. Discrimination of CSN3
      alleles A and B was also obtained by DNA SSCP analysis. Sequencing of CSN3(B)
      revealed four transitions at position 247, 309, 471, and 591 compared with
      CSN3(A). From these transitions, the following amino acid substitutions are
      deduced: 44 Gln --> Arg, 65 Val --> Ile, 119 Val --> Ile, and 159 Ser --> Pro.
      Among the four mutations, only the 44 Gln --> Arg can be revealed by milk protein
      IEF analysis while at DNA level three further genetic variants should exist in
      addition to CSN3(A) and CSN3(B).

PMID- 11531705
TI  - Complete genomic sequence of the bovine prion gene (PRNP) and polymorphism in its
      promoter region.

PMID- 11531706
TI  - Isolation, characterization and mapping of the bovine signal peptidase subunit 18
      gene.

PMID- 11531707
TI  - Intensive cardiopulmonary support for otherwise dying post-heart and lung
      transplant recipients with extracorporeal membrane oxygenation.

PMID- 11531708
TI  - Mechanical bridge with extracorporeal membrane oxygenation and ventricular assist
      device to heart transplantation.
AB  - The aim of this study was to evaluate the effect of double bridges with
      extracorporeal membrane oxygenation (ECMO) and ventricular assist devices (VADs)
      in clinical heart transplantation. Between May 1994 and October 2000, 134
      patients underwent heart transplantation at the National Taiwan University
      Hospital. Ten patients received ECMO or VAD support as bridges to
      transplantation. The ages ranged from 3 to 63 years. The indications included
      cardiac arrest under cardiopulmonary resuscitation in 2 and profound cardiogenic
      shock refractory to conventional therapy in 8 patients. Usually ECMO was first
      set up as rescue therapy. If ECMO could not be weaned off after short-term
      (usually 1 week) support, suitable VADs (HeartMate or Thoratec VAD) were
      implanted for medium-term or long-term support. Five patients received ECMO
      support as emergency rescue for 2 to 9 days, and then moved to Thoratec VAD for
      8, 49, and 55 days, respectively, or centrifugal VAD for 31 days, or HeartMate
      VAD for 224 days. They all survived. The survival rate of double bridges with
      ECMO and VAD was 100%. In postcardiotomy cardiogenic shock, circulatory collapse
      from acute myocardial infarction or myocarditis, ECMO is the device of choice for
      short-term support. If heart transplantation is indicated, VADs should replace
      ECMO for their superiority as a bridge to heart transplantation. Our preliminary
      data of double bridges with ECMO and VAD revealed good results and were reliable
      and effective bridges to transplantation.

PMID- 11531709
TI  - Development of a totally implantable pulsatile centrifugal pump as a ventricular
      assist device.
AB  - The Taita No. 1 ventricular assist device (T-VAD) is a totally implantable
      pulsatile impeller centrifugal pump driven by a magnetically suspended motor. The
      flow can achieve 2.01 +/- 0.17 L/min against a pressure of 100 mm Hg under 0.266
      +/- 0.017 amp and 13.55 +/- 0.41 voltage. The speed was around 3,500 rpm. It
      consumed less than 6 W of power, resulting in less heat production and mechanical
      bearing complications. The impeller vane was designed to have both radial and
      axial curves according to the stream surface and stream lines to reduce
      thrombosis and hemolysis. Eight calves weighing 80 to 100 kg (mean 87 +/- 12 kg)
      were used for experiments. With the calves under general anesthesia, left
      posterolateral thoracotomy was performed to connect the inflow tube with the
      atrial appendage and to anastomose the outflow tube with the descending aorta.
      The calves usually awoke and stood up within hours after discontinuation of
      anesthetics. The mean survival of the calves was 75 +/- 42 days (range 33-148
      days). The terminations of experiments were mainly due to infection. During the
      course of pumping, no significant deterioration of liver or renal function was
      noted. The evaluation of serum samples from the implanted calves indicated that
      hemolysis was not associated with use of the T-VAD. The average daily free
      hemoglobin level was 8.08 +/- 3.05 mg/dl, which was less than the set limit of 20
      mg/dl. The red blood cell and platelet count and hemoglobin of implanted animals
      were within the normal range. In our results, the T-VAD provided competent
      pulsatile function without severe blood damage or organ dysfunction.

PMID- 11531710
TI  - Replacing cardiopulmonary bypass with extracorporeal membrane oxygenation in lung
      transplantation operations.
AB  - Cardiopulmonary bypass (CPB) is required in some lung transplantation (LTx)
      operations. However, it increases risks of bleeding and early graft dysfunction.
      We report our experiences of replacing CPB with heparin-bound extracorporeal
      membrane oxygenation (ECMO) in LTx operations. If extracorporeal circulation was
      anticipated for the LTx operations, ECMO support was set up through the femoral
      venoarterial route after induction of anesthesia; then, LTx was done as usual.
      Five thousand units of heparin was injected intravenously during the femoral
      vessels cannulation, but no more was used during the first 24 h of ECMO support.
      If necessary, as in patients undergoing single LTx for end-stage pulmonary
      hypertension, the ECMO support was directly extended into the postoperative
      period until reperfusion edema of the graft lung subsided. Twelve single LTxs and
      3 bilateral sequential single LTxs were done under ECMO support. The advantages
      of using femoral ECMO rather than conventional CPB in LTx operations were the
      operative field was not disturbed by the bypass cannula, stable cardiopulmonary
      function and normothermia were maintained throughout the operations, there were
      less blood loss and transfusion requirements, and the left LTx was as easily
      performed as the right LTx. Red blood cell transfusion requirements during the
      operation and the first postoperative day were 4.4 +/- 2.8 and 2.4 +/- 2.0 U,
      respectively, in 10 adult patients undergoing uncomplicated single LTx with ECMO
      support, and 4.3 +/- 1.3 and 1.5 +/- 1.5 U in 8 adult patients undergoing single
      LTx without any extracorporeal circulatory support. The difference was not
      significant between the 2 groups (p = 0.53 and 0.32 by Mann-Whitney U test). The
      ECMO did not increase blood transfusion requirements. In comparison, 13 U of red
      blood cell transfusion was required in 2 patients receiving single LTx under CPB
      support. The ECMO support made the postoperative critical care easier in
      recipients with graft lung edema. Except for 2 cases of primary graft failure,
      the ECMO could be weaned off and removed at bedside within a short period (27.9
      +/- 24.6 h, n = 13) with no major complications. In conclusion, the heparin-bound
      femoral ECMO rather than CPB should be used for LTx operations unless concomitant
      cardiac repair is planned.

PMID- 11531711
TI  - Physiologic analysis of cardiac cycle in an implantable impeller centrifugal left
      ventricular assist device.
AB  - The purpose of this study was to determine the physiologic relationship between
      the cardiac cycle and the nonpulsatile impeller centrifugal Taita No.1 left
      ventricular assist device (T-LVAD) in a chronic animal study. The relationship of
      the cardiac cycle, pump flow, aortic pressure, left ventricle pressure, and pump
      power were analyzed by 5 phases in 4 stages. The isovolumetric ventricular phase
      is from mitral valve closure (MVC) to aortic valve opening (AVO) and is called
      Stage 1. The ejection phase is from AVO to aortic valve closure (AVC) and is
      called Stage 2. The isovolumetric relaxation phase is from AVC to MVC and is
      called Stage 3. The passive filling and atrial contraction phase is from MVC to
      mitral valve opening (MVO) and called Stage 4. Based on evidence from the
      physiologic volume change of the left ventricle, the change of pump flow of the T
      LVAD in a cardiac cycle by variable voltages of pump control was evaluated using
      animal models. After left posteriolateral thoracotomy via the fifth intercostal
      space under general anesthesia, the nonpulsatile centrifugal T-LVAD was implanted
      into 2 healthy calves. The inflow of the T-LVAD was inserted into the left
      ventricle through the mitral valve via the left atrial appendage. The arterial
      blood pressure waveform was measured and recorded on the outflow of the T-LVAD.
      The 4 phases of a cardiac cycle were defined as MVC-AVO (Stage 1), AVO-AVC (Stage
      2), AVC-MVO (Stage 3) and MVC-MVO (Stage 4) according to the outflow pressure of
      the outflow of the T-LVAD and differential pressure between the outflow and
      inflow of the T-LVAD. We carried out the real-time waveform measurement for
      electrocardiogram, the outflow pressure, the T-LVAD flow and the speed, as well
      as open loop and constant voltage (V). In a cardiac cycle, the sensing current of
      the T-LVAD was inverse to the speed. The flow of the T-LVAD at the 4 stages was
      measured individually and analyzed with different control voltages from 10 to 18
      V. The highest flow ratio of MVC-AVC/AVC-MVC was noted when the T-LVAD worked on
      14 V. By using analysis methodology of the flow ratio of a cardiac cycle, the
      optimal physiologically effective control of the T-LVAD might be achieved.

PMID- 11531712
TI  - Growth of endothelial cells on different concentrations of Gly-Arg-Gly-Asp
      photochemically grafted in polyethylene glycol modified polyurethane.
AB  - To improve endothelial cell adhesion and growth on the surface of polyethylene
      glycol modified polyurethane (PU-PEG), cell adhesive peptide Gly-Arg-Gly-Asp
      (GRGD) was photochemically grafted to the surface. The surface grafted GRGD-N
      Succinimidyl-6-[4'-azido-2'-nitrophenylamino]hexanoate (SANPAH) on a PU-PEG
      surface was performed by adsorption and subsequent ultraviolet irradiation.
      Fourier transform infrared spectra (FTIR) and electron spectroscopy for chemical
      analysis (ESCA) confirmed the GRGD grafted to form a PU-PEG-GRGD surface. The
      composition fraction of nitrogen calculated from ESCA analysis for the PU-PEG
      GRGD surface was well correlated with the concentration of GRGD to be
      immobilized. Human umbilical vein endothelial cells (ECs) were well adhered and
      growing on the PU-PEG-GRGD surface. Moreover, the viability of ECs growing on PU
      PEG-GRGD surfaces, analyzed by MTT test, was also well correlated with the GRGD
      concentrations immobilized on the surface. With photochemical techniques, we
      could manipulate different contents of GRGD to form multiple regions of PU-PEG
      GRGD surface that could enhance the growth of ECs on the surface, and the
      enhancement efficiency was well correlated with GRGD contents.

PMID- 11531713
TI  - Application of extracorporeal membrane oxygenation in adult burn patients.
AB  - Adult respiratory distress syndrome (ARDS) has been the major cause of mortality
      in burn injury. The authors reported the experience of using extracorporeal
      membrane oxygenation (ECMO) to treat adult burn patient with ARDS. Three patients
      with burn or electric injury, around 48.9% of body surface area over second
      degree burns, developed ARDS after resuscitation. All had positive blood culture
      and depended on a ventilator more than 5 days before ECMO. Venovenous (VV) ECMO
      was started at the beginning of severe respiratory failure with an oxygen index
      of 61.6 +/- 15.5 cm H2O/mm Hg (> or =40 cm H2O/mm Hg), partial arterial oxygen
      tension to inspired oxygen fraction (Pa(O2)/Fi(O2)) of 46.1 +/- 7.0 mm Hg (< or
      =200 mm Hg), positive end expiratory pressure (PEEP) of 15.7 +/- 1.6 cm H2O (> or
      =10 cm H2O), alveolar-arterial difference in oxygen concentration (A-a D(O2)) of
      618.9 +/- 19.3 mm Hg (> or =300 mm Hg), and lung compliance of 17.3 +/- 4.6 ml/cm
      H2O (< or =30 ml/cm H2O). The VV type had to be converted to the newly designed
      veno-venoarterial (V-VA) ECMO due to the myocardial dysfunction. Two of three
      patients survived. The duration of ECMO was 160.2 +/- 51.1 h. Two patients
      received debridement of escar during ECMO support and desmopressin infusion, and
      no increased bleeding or coagulopathy was found. The respiratory parameters were
      significantly improved after ECMO, especially in the survivors. ECMO is also
      suitable for ARDS in adult burn injury.

PMID- 11531714
TI  - New application of heparin-bonded extracorporeal membrane oxygenation in
      difficult neurosurgery.
AB  - We wished to evaluate the safety and the advantages of using heparin-bonded
      extracorporeal membrane oxygenation (ECMO) to replace conventional
      cardiopulmonary bypass (CPB) in deep hypothermic circulation for complex cerebral
      aneurysm surgery.Heparin-bonded ECMO without the bridging tube and the cardiotomy
      reservoir was set up through the femoral vessels. Limited heparin was infused. In
      deep hypothermia, the ECMO blood flow was temporarily decreased as low as the
      neurosurgeons' request. It was applied to 4 patients with difficult intracranial
      aneurysms who were selected for the procedure. Clipping, wrapping, or vascular
      bypass was implemented to manage the aneurysms under deep hypothermia. The total
      heparin dosage used in the whole procedure was 9,875 +/- 1,625 U, and the mean
      ECMO time was 270 +/- 105 min. The blood consumption was packed red blood cell
      3.0 +/- 0.5 U and fresh frozen plasma 3.8 +/- 2.3 U. Compared with our previous
      experiences using conventional CPB, ECMO did need less heparin and blood
      transfusions. Clipping was applied in 2 patients, wrapping in 1, and venous graft
      interposition was performed in 1. Mortality occurred in 1 patient (25%) due to
      brain herniation. This preliminary study suggested that the heparin-bonded ECMO
      without reservoir in deep hypothermia could be safe in cerebral aneurysm surgery
      under a low flow circuit.

PMID- 11531715
TI  - New trends in extracorporeal membrane oxygenation in newborn pulmonary diseases.
AB  - New trends in extracorporeal membrane oxygenation (ECMO) for respiratory failure
      in the newborn were reviewed. Following a decade of clinical research, ECMO is
      now the standard treatment for newborn respiratory failure when all other
      conventional less-invasive treatment options have been exhausted. As of July
      2000, 15,525 newborns with respiratory failure treated with ECMO have been
      entered into the registry of the Extracorporeal Life Support Organization with an
      overall survival rate of 78%. The latest improvement in ECMO technology in this
      group of patients includes minimally invasive modes of vascular access through
      percutaneous approaches to minimize morbidity. However, with advances in modes of
      mechanical ventilation, including high-frequency ventilation and the introduction
      of inhaled nitric oxide, the use and necessity for ECMO have clearly diminished
      for newborn respiratory failure.

PMID- 11531716
TI  - Lateral approach without ligament release in total knee arthroplasty: new
      concepts in the surgical technique.
AB  - A lateral approach without ligament release was performed in 475 primary total
      knee arthroplasties (TKAs) in 344 patients and 50 revision TKAs in 39 patients.
      Deformities of the genu varum or valgum were corrected by accurate bone cut; no
      ligament releases were required other than to achieve adequate exposure. A
      lateral approach allowed both self-centering of the extensor mechanism and knee
      closure in complete flexion. Better range of motion was achieved. More than 90
      degree active flexion usually occurred 3 days postoperatively. Postoperative
      roentgenograms showed all knees had good varus and valgus stability, which was
      sustained with time, except 1 with late genu recurvatum due to inadequate
      polyethylene thickness and the other with a broken tibial base plate.
      Complications such as disruption of patellar blood supply and knee instability,
      more frequently observed in the medial approach with ligament release, did not
      occur. The results suggest that this new technique is safe and may give better
      outcomes.

PMID- 11531717
TI  - Osteogenic evaluation of glutaraldehyde crosslinked gelatin composite with fetal
      rat calvarial culture model.
AB  - The cytotoxicity of the synthetic bone substitute composed of tricalcium
      phosphate and glutaraldehyde crosslinked gelatin (GTG) were evaluated by
      osteoblast cell culture. In a previous study, the GTG composites were soaked in
      distilled water for 1, 2, 4, 7, 14, 28, and 42 days, and then the solutions (or
      extracts) were cocultured with osteoblasts to evaluate the cytotoxicity of GTG
      composites by alive cell counting. In this study, the extracts were cocultured
      with the osteoblasts; thereafter, the concentration of transforming growth factor
      beta (TGF-beta1) and prostaglandin E2 (PGE2) in the medium was analyzed to
      strictly reflect the biological effects of GTG composites on the growth of
      osteoblasts. In order to investigate the osteoconductive potential of the GTG
      composites on new bone formation in a relative short term, a model of neonatal
      rat calvarial organ culture was designed prior to animal experiments. Three
      experimental materials of 4, 8, and 12% GTG composites were evaluated by fetal
      rat calvarial organ culture for their ability for bone regeneration.
      Deproteinized bovine and porcine cancellous bone matrixes were used as the
      controlled materials. All the organ culture units were maintained in cultured
      medium for 5 weeks. Following the culture period, the morphology of tissue was
      observed under an optical microscope, and the quantitative evaluation of the new
      generation bone was determined by using a semiautomatic histomorphometeric
      method. Except in the initial 4 days, the concentration of TGF-beta1 of 4% and 8%
      GTG composites was higher than that of the blank group for all the other
      experimental time periods. The PGE2 concentration for 4% and 8% GTG composites
      was lower than that of the blank group. It revealed that the 4% and 8% GTG
      composites would not lead to inflammation and would promote osteoblast growth.
      The morphology and activity of the osteoblasts were not transformed or changed by
      the 2 GTG composites. For the 12% GTG composite, the performance of the in vitro
      condition was inferior to the blank group and the other 2 GTG composites.
      Although the concentration of TGF-beta1 and PGE2 was gradually back to normal
      after 14 days, the morphology of the osteoblasts was abnormal with features such
      as contracted cytoplast structures. The osteoblast was damaged perhaps in the
      initial stage. We suggested that the 4% and 8% GTG composites should be soaked in
      distilled water at least for 4 days before medical applications. The 12% GTG
      composite and the composites with a concentration of glutaraldehyde solution
      higher than 12% were not recommended as a medical prostheses in any condition.
      The fetal rat calvaria culture also showed the same results with the analysis of
      TGF-beta1 and PGE2. From the study, we could predict the results of animal
      experiments in the future.

PMID- 11531718
TI  - Experimental evaluation of the V-point heparin-bonding system applied to a dense
      membrane artificial lung during 24-hour extracorporeal circulation in beagles.
AB  - Heparin was covalently bonded to a hollow-fiber dense-membrane artificial lung
      and circuit using a silane coupling agent and polyethyleneimine as a spacer. This
      study investigated whether the novel artificial lung could sustain prolonged
      extracorporeal lung assist (ECLA) by venoarterial bypass in beagles using minimal
      anticoagulants. We maintained ECLA for 24 h in 3 groups of minimal systemic
      heparinization, heparinization with the new anticoagulant nafamostat mesilate,
      and without any systemic anticoagulant. The results were assessed from the
      functional performance of the artificial lung and by macroscopic and microscopic
      examination after the experiments. Artificial lung function, hemodynamics,
      hemogram, and platelet aggregation activity were well maintained in all groups.
      There was no plasma leakage from the artificial lung. Although several clots were
      observed in stagnant areas of the artificial lungs and circuits, there was no
      clot formation inside the artificial lung in any group. This highly
      biocompatible, heparin-bonded dense-membrane artificial lung performed well and
      safely during prolonged ECLA with blood clotting times less than 120 s.

PMID- 11531719
TI  - Initial stability of a cementless acetabular cup design: experimental
      investigation on the effect of adding fins to the rim of the cup.
AB  - Different design solutions have been suggested for improvement of the initial
      stability of cementless acetabular cups, such as adding threads, spikes, or pegs
      to the hemispherical geometry, the pore structure of the surface; and screw
      fixation. This experimental study investigated the effect of fins on the initial
      stability of the acetabular cup. Three designs were studied, with none, 2, and 12
      fins, respectively. The cups were press fit into cavities reamed in 2 different
      polyurethane foams, used to simulate 2 qualities of cancellous bone. Two
      millimeter press-fit and exact-fit conditions were investigated. The results show
      that the type of substrate and the interference value are important in
      determining the initial stability of the cup. The addition of fins on the cup rim
      enhances in vitro the initial stability, especially in cases of a poor press fit
      with a good substrate. This preclinical investigation suggests that the use of a
      cup design with fins may be beneficial in all cases in which press fit of the cup
      cannot be assured. However, further clinical studies are required to validate in
      vivo the efficacy of the fins as additional fixation devices.

PMID- 11531720
TI  - Can we manage without the mental hospital?
AB  - OBJECTIVES: Many developed countries, having invested massively in psychiatric
      hospitals in the past 150 years, are in the process of dismantling them. The
      central question is whether this change in the location of care from the
      psychiatric hospital to district-based services has benefited the patients. The
      objectives of this review are to examine the evidence on which an answer to the
      above question might be based. METHOD: Much of the relevant research comes from
      the 13-year programme of the Team for the Assessment of Psychiatric Services
      conducted in London, but other research will be reviewed as appropriate. RESULTS
      AND CONCLUSIONS: Long-stay, non-demented patients, including the elderly, enjoy a
      better quality of life in the community homes compared with the psychiatric
      hospitals. Public attitudes constitute an obstacle to social integration into the
      healthy community, but can be ameliorated with local educational programmes. The
      provision of work has been unsatisfactory, but the development of social firms
      holds some promise. Patients with dementia receive better care in community
      nursing homes compared with hospital wards, according to their relatives'
      opinions, backed up by observational studies. The part of the service which is
      most unsatisfactory is the admission facilities. This is due to a variety of
      causes, including a failure to plan for the admission needs of discharged long
      stay patients, the virtual absence of rehabilitation units in the community and
      an inadequate provision of a range of sheltered accommodation. However, these
      problems could be resolved with adequate investment in innovative facilities.

PMID- 11531721
TI  - Can research influence mental health policy?
AB  - OBJECTIVE: This paper describes the processes involved in policy development and
      implementation with examples of how this can be influenced by the outcomes of
      research. METHOD: The author draws on his experience in the development and
      implementation of Australia's National Mental Health Policy and on the literature
      describing public policy analysis. RESULTS: A five-step process of problem
      identification, policy development, political decision, policy implementation and
      evaluation is described. This process identifies how issues are considered,
      adopted and implemented by governments. CONCLUSION: An understanding of this
      process can inform mechanisms by which scientific research can impact on the
      issues considered and the decisions made in each step of policy analysis and
      development.

PMID- 11531722
TI  - Psychiatric assessment in remote Aboriginal communities.
AB  - OBJECTIVE: The objective of this study was to describe the psychiatric assessment
      of Aboriginal patients from remote Aboriginal communities in Central Australia.
      METHOD: The method consisted of a summary of the experiences gained during a
      dissertation year placement as senior registrar with the Northern Territory
      Remote Area Mental Health Team. RESULTS: Remote area Aboriginal psychiatry
      entails learning a whole new set of skills in terms of history taking and the
      mental state examination, a knowledge of the importance of extended kinship ties
      and cultural issues, the use of Aboriginal mental health workers as partners in
      assessing and managing patients via their families and accepting referrals from a
      wide range of sources. CONCLUSIONS: Working on a service providing psychiatric
      care to remote area Aboriginal communities can be a deeply rewarding personal and
      professional experience.

PMID- 11531723
TI  - Outpatient cognitive behavioural therapy programme for alcohol dependence: impact
      of naltrexone use on outcome.
AB  - OBJECTIVE: Cognitive-behavioural therapy (CBT) has been effectively used in the
      treatment of alcohol dependence. Clinical studies report that the anticraving
      drug naltrexone, is a useful adjunct to treatment. Currently, few data are
      available on the impact of adding this medication to programmes in more typical,
      outpatient, and rehabilitation settings. The objective of this study was to
      examine the impact on outcome of adding naltrexone to an established outpatient
      alcohol rehabilitation program which employed CBT. METHOD: Fifty patients
      participated in an established 12-week, outpatient, 'contract'-based alcohol
      abstinence programme which employed CBT. They also received naltrexone 50 mg
      orally daily (CBT + naltrexone). Outcomes were compared with 50 historical,
      matched controls, all of whom participated in the same programme without an
      anticraving medication (CBT alone). All patients met DSM-IV criteria for alcohol
      dependence. RESULTS: Programme attendance across the eight treatment sessions was
      lower in the CBT alone group (p < 0.001). Relapse to alcohol use occurred sooner
      and more frequently in the CBT alone group (p < 0.001). Rehabilitation programme
      completion at 12 weeks was 88% (CBT + naltrexone) compared with 36% for (CBT
      alone) (p < 0.001). Alcohol abstinence at 12 weeks was 76% (CBT + naltrexone)
      compared with 18% (CBT alone) (p < 0.001). CONCLUSION: When employing the same
      outpatient rehabilitation programme and comparing outcomes using matched
      historical controls, the addition of naltrexone substantially improves programme
      attendance, programme completion and reported alcohol abstinence. In a typical
      outpatient programme, naltrexone addition was associated with significantly
      improved programme participation, better outcomes and was well tolerated.

PMID- 11531724
TI  - Improving community-based services for older patients with depression: the
      benefits of an educational and service initiative.
AB  - OBJECTIVE: The objective of this study was to report a quality improvement
      project for older patients with depression. The initiative focused on both
      clinical practice changes (improvement of medical, neurocognitive and behavioural
      assessment) and service development (greater continuity of care). METHOD: After
      initial identification of key deficits, implementation of a service and
      educational initiative took place within a district mental health service. The
      service consisted of an inpatient unit, a specialized psychogeriatric service and
      two adult community mental health services. Mental health staff received
      education regarding the specific needs of older patients with depression and were
      provided with assessment materials, patient education and treatment aids. General
      practitioners participated in shared long-term management. RESULTS: Following
      graded implementation, the management of 44 subjects (mean age = 65.4 years, 91%
      female) recruited over an 8-month period was reviewed. Compared with 99 subjects
      (mean age = 68.9 years, 69% female) from the earlier 12-month assessment phase,
      there were significant improvements in medical (43% to 92%), neurocognitive (37%
      to 84%) and behavioural (e.g. suicidal ideation: 78% to 100%) assessments.
      Similarly, relevant laboratory investigations (neuroimaging: 21% to 67%) and
      communication with general practitioners (73% to 97%) improved. The most change
      occurred in the adult community-based treatment services. CONCLUSIONS: A
      coordinated management and educational initiative resulted in marked improvement
      in basic medical and psychiatric assessment and more integrated care. These
      changes did not require expansion of specialist services.

PMID- 11531725
TI  - Predictors of partially met or unmet need reported by consumers of mental health
      services: an analysis of data from the Australian National Survey of Mental
      Health and Wellbeing.
AB  - OBJECTIVE: We examined data from the 1997 National Survey of Mental Health and
      Wellbeing to identify factors associated with consumers of mental health help
      reporting that their needs were unmet or only partially met. Predictor factors
      included sociodemographic variables, psychological morbidity measures and type of
      health practitioner seen. METHOD: Five types of mental health help were
      considered: information, medication, psychological therapy, social interventions
      and skills training. A respondent's unmet need for each type of mental health
      help was given one of three values: 0: no unmet need reported; 1: some but not
      enough help of this type provided; and 2: no help of this type provided although
      it was needed. Multiple ordered logistic regressions were undertaken to identify
      predictor variables associated with reporting unmet need for each type of help.
      RESULTS: Few sociodemographic factors were found to be associated with consumers
      reporting unmet need for mental health help. Those with less education were more
      likely to report unmet need for medication. Being male, living alone and being
      unemployed were associated with unmet need for skills training. Having seen a
      general practitioner for mental health reasons was found to be associated with
      reporting unmet need for both information and social interventions. Self
      identifying, or being diagnosed, as having an anxiety disorder was associated
      with reporting unmet need for four of the five types of help. CONCLUSIONS: In
      this exploratory analysis, we examined factors associated with consumers of
      mental health help reporting that their needs were unmet or partially met. We
      found that the needs of those with anxiety problems were not generally well met.
      Our findings also indicate there is a need to continue to improve collaboration
      between the medical and community services sectors.

PMID- 11531726
TI  - Restraint practices in Australasian emergency departments.
AB  - OBJECTIVE: The objective of this study was to estimate the use of restraint
      techniques and evaluate restraint policies and training in Australasian emergency
      departments METHOD: A survey of 116 Australasian emergency departments was
      conducted to determine the type, indications/contraindications, training,
      policies, documentation and audit requirements for restraint. RESULTS: The
      overall estimated rate of patient restraint is 3.3 episodes per 1000
      presentations. The commonest indications for restraint are violence or threatened
      violence (52%), psychosis (32%) and acute brain syndrome (10%). Major
      contraindications are medical instability, risk of harm to staff in applying
      restraint and the availability of alternatives to restraint. Chemical restraint
      is used in all emergency departments surveyed. The commonest agents used are
      haloperidol (93%), midazolam (82%) and diazepam (59%). At least one
      benzodiazepine and one major tranquilliser are used in 97% of emergency
      departments. Manual restraint (87%) is frequently used as a prelude to chemical
      or, less frequently, mechanical restraint (69%). Seclusion restraint is used in
      23% of Australasian emergency departments. Formal training is most commonly
      undertaken for chemical restraint, being used in 33% of departments surveyed.
      Less than half of the departments have written policies guiding the use of
      restraint, and only 11% audit their use of restraint. A specific form for
      restraint documentation is used in only one emergency department. CONCLUSIONS:
      Patient restraint is a common procedure in Australasian emergency departments.
      There is little formal training in, or documentation or audit of, restraint
      practices in Australasian emergency departments, despite the important clinical,
      occupational health and medical legal issues associated with the use of
      restraint.

PMID- 11531727
TI  - How reliable are reported plasma clozapine levels?
AB  - OBJECTIVE: Many practitioners use plasma levels to determine the optimum dosage
      of clozapine. The aim of this study was to determine the intra- and
      interlaboratory accuracy in assaying samples of clozapine dissolved in human
      plasma. METHOD: Three samples were sent to one laboratory to obtain an initial
      determination of accuracy (phase I). Then samples of clozapine dissolved in human
      plasma were prepared at concentrations of 140, 310 and 580 ng/mL and dispatched
      on dry ice to 10 assaying centres in Australia and New Zealand. The results of
      the survey were analysed and posted to each centre (phase II). The programme was
      repeated using concentrations of 160, 380 and 640 ng/mL (phase III). Samples
      prepared in purified water and freeze-dried samples were also dispatched.
      RESULTS: In phase II there were two centres with results significantly different
      from the mean. In phase III all the centres returned concordant results. There
      was a high level of consistency in the measurement of samples with a maximum
      coefficient of variation of 0.16. The concentrations determined by the centres,
      however, were significantly lower than the nominal concentrations of the prepared
      solutions. CONCLUSIONS: Clinicians in Australia and New Zealand who wish to know
      their patients' plasma-clozapine levels can be confident that the result of the
      assay is unlikely to vary with the choice of centre or the operator who performs
      the assay.

PMID- 11531728
TI  - Screening for depression in the medically ill: the suggested utility of a
      cognitive-based approach.
AB  - OBJECTIVE: There is a need for a valid measure of depression in the medically
      ill, and one that is independent of medical illness characteristics. As yet,
      there is no such widely accepted measure. We thus report on the early development
      of such a measure using cognitive constructs that define depressive mood state
      nuances. METHOD: We studied 67 patients with a significant medical illness,
      verbally administering a set of 81 provisional items. Sample members also
      alternatively completed one of two comparison measures: the Hospital Anxiety and
      Depression Scale (HADS) or the Beck Depression Inventory for Primary Care (BDI
      PC). A psychiatrist interviewed a subset to determine severity of any depression
      and whether subjects met formalized caseness criteria for depression. The
      Composite International Diagnostic Interview (CIDI) was also administered during
      interviews to assess agreement with psychiatrist judgements about caseness.
      RESULTS: A 16-item measure with high internal consistency was derived, with
      validation analyses suggesting it was distinctly superior to the HADS and
      somewhat superior to the BDI-PC measure. CONCLUSIONS: A cognitive-based approach
      (as used by both our measure and the BDI-PC) to screen for depression in
      medically ill groups appears to have distinct utility in identifying depressed
      patients, and in avoiding confounding influences of physical symptoms.

PMID- 11531729
TI  - Mind over matter? I: philosophical aspects of the mind-brain problem.
AB  - OBJECTIVE: To conceptualize the essence of the mind-body or mind-brain problem as
      one of metaphysics rather than science, and to propose a formulation of the
      problem in the context of current scientific knowledge and its limitations.
      METHOD AND RESULTS: The background and conceptual parameters of the mind-body
      problem are delineated, and the limitations of brain research in formulating a
      solution identified. The problem is reformulated and stated in terms of two
      propositions. These constitute a 'double aspect theory'. CONCLUSIONS: The problem
      appears to arise as a consequence of the conceptual limitations of the human
      mind, and hence remains essentially a metaphysical one. A 'double aspect theory'
      recognizes the essential unity of mind and brain, while remaining consistent with
      the dualism inherent in human experience.

PMID- 11531730
TI  - Mind over matter? II: implications for psychiatry.
AB  - OBJECTIVE: To explore concepts of causality within the mind and aetiology of
      psychiatric disorders in the light of the proposed formulation of the mind-brain
      problem. METHOD: Taking the two propositions of this formulation as 'first
      principles' a logical analysis is attempted. RESULTS AND CONCLUSIONS: Neural
      activity cannot in principle be regarded as causing mental activity, or vice
      versa. Causal processes are most coherently conceptualised in terms of the 'mind
      brain' system. Determination of causal and aetiological effects will always
      necessitate consideration of contextual evidence. Because of the 'explanatory
      gap' between explanation in neurophysiological terms and 'mentalistic' terms,
      whenever formulation in mentalistic terms is possible this will carry greater
      explanatory power; that is, it will carry meaning in the way a neural formulation
      cannot.

PMID- 11531732
TI  - Gender differences in the relationship between depression and suicidal ideation
      in young adolescents.
AB  - OBJECTIVE: This study examined the risk relationship between depressive
      symptomatology and suicidal ideation for young adolescent males and females.
      METHOD: A large cohort of students in their first year of high school completed
      the Center for Epidemiological Studies Depression Scale (CES-D) and the
      Adolescent Suicide Questionnaire. The risk relationship between depressive
      symptomatology and suicidal ideation was modelled using non-parametric kernel
      smoothing techniques. RESULTS: Suicidal ideation was more frequently reported by
      females compared with males which was partly explained by females having higher
      mean depression scores. At moderate levels of depression females also had a
      significantly higher risk of suicidal ideation compared with males and this
      increased risk contributed to the overall higher levels of female ideation.
      CONCLUSIONS: The risk relationship between depressive symptomatology and suicidal
      ideation is different for young adolescent males and females. The results
      indicate that moderate levels of depressive symptomatology can be associated with
      suicidal ideation (especially among young females) and that for these young
      people a suicide risk assessment is required.

PMID- 11531733
TI  - Timing, space and ADHD: the dopamine theory revisited.
AB  - OBJECTIVE: The objective of this study was to review the dopamine theory of
      attention deficit hyperactivity disorder (ADHD) in terms of advances made over
      the last decade. METHOD: 'Hyper' and 'hypo' dopaminergic theories are discussed,
      as well as noradrenergic and neuropsychological findings in ADHD. A model
      incorporating both anterior and posterior attention systems, involved in
      orienting, inhibition, vigilance and working memory, is described.
      Neuropsychological studies of covert orienting are reviewed. RESULTS: The
      dopamine theory is supported by neuroimaging, genetic and stimulant medication
      studies, which confirm an inhibitory dopaminergic effect at striatal/prefrontal
      level. Work in rodents and primates, as well as humans has shown that
      noradrenergic systems are also important in prefrontal regulation, in particular
      alpha(2A) noradrenergic agonists have a beneficial effect on cognitive tasks.
      Neuropsychological studies implicate posterior parietal mechanisms in the
      orienting of attention. Working memory may require integration of spatial and
      temporal information, involving anterior and posterior systems. CONCLUSIONS:
      Anterior and posterior attention systems are involved in inhibition, working
      memory and orientation. Attention deficit hyperactivity disorder symptoms and
      subtypes are likely to reflect deficits in both inhibition and working memory,
      and may be heterogeneous. While the dopamine theory is supported by genetic and
      stimulant medication studies, the work of Arnsten and colleagues suggests a
      potential role for alpha(2) noradrenergic agonists such as guanfacine.

PMID- 11531734
TI  - First-episode psychosis in the military: a comparative study of prodromal
      symptoms.
AB  - OBJECTIVE: The objective of this study is to provide a retrospective description
      of prodromal symptoms of young military servicemen with first-episode psychosis,
      and a comparison with first-episode non-psychotic disorders. METHOD: Thirty
      consecutive servicemen presenting with first-episode psychosis were studied.
      Thirty-four randomly selected servicemen from 123 with non-psychotic disorders
      served as comparison. A combination of unstructured and semistructured interviews
      with the patient and other informants was used to describe the prodromal
      symptoms. RESULTS: The most common prodromal psychotic symptoms were social
      withdrawal (83%); anxiety (77%); sleep disturbance (77%); disturbance in
      attention, concentration or memory (73%); deterioration in studies in school
      (70%); depressed mood (63%); odd behaviour (53%); and anger or irritability
      (53%). Common symptoms found in first-episode psychosis and non-psychotic
      patients included sleep disturbance, anxiety, depressed mood and anger or
      irritability. Common symptoms that were associated with the psychotic prodrome
      were social withdrawal (p < 0.001), deterioration in school results (p < 0.001)
      and disturbance in attention, concentration or memory (p < 0.001). The psychotic
      prodrome was also associated with apathy (p < 0.001), odd behaviour (p < 0.001),
      doing nothing (p = 0.004) and thought blocking (p = 0.04). CONCLUSION: Cognitive
      disturbances and attenuated negative symptoms appear to be more specific to the
      psychotic prodrome in young patients with first-episode psychosis.

PMID- 11531735
TI  - What is chronic fatigue syndrome? Heterogeneity within an international
      multicentre study.
AB  - OBJECTIVE: We sought to compare the characteristics of patients presenting with
      chronic fatigue (CF) and related syndromes in eight international centres and to
      subclassify these subjects based on symptom profiles. The validity of the
      subclasses was then tested against clinical data. METHOD: Subjects with a
      clinical diagnosis of CF completed a 119-item self-report questionnaire to
      provide clinical symptom data and other information such as illness course and
      functional impairment. Subclasses were generated using a principal components
      like analysis followed by latent profile analysis (LPA). RESULTS: 744 subjects
      returned complete data sets (mean age 40.8 years, mean length of illness 7.9
      years, female to male ratio 3:1). Overall, the subjects had a high rate of
      reporting typical CF symptoms (fatigue, neuropsychological dysfunction, sleep
      disturbance). Using LPA, two subclasses were generated. Class one (68% sample)
      was characterized by: younger age, lower female to male ratio; shorter episode
      duration; less premorbid, current and familial psychiatric morbidity; and, less
      functional disability. Class two subjects (32%) had features more consistent with
      a somatoform illness. There was substantial variation in subclass prevalences
      between the study centres (Class two range 6-48%). CONCLUSIONS: Criteria-based
      approaches to the diagnosis of CF and related syndromes do not select a
      homogeneous patient group. While substratification of patients is essential for
      further aetiological and treatment research, the basis for allocating such
      subcategories remains controversial.

PMID- 11531736
TI  - Traumatic stress and ways of coping of community residents exposed to a train
      disaster.
AB  - OBJECTIVES: The aims of this study were to examine the degree of traumatic stress
      and the coping strategies employed by community residents who lived on both sides
      of a rail track where a train collision occurred in 1996 in Stafford, UK. The
      hypothesis was that there would be a high level of traumatic stress and that
      emotion-focused coping would be the predictor to distress. METHOD: This was a
      cross-sectional survey with a retrospective design in which 66 community
      residents, who lived between 30 and 100 feet away from the crash site, were
      interviewed. The study began approximately 7 months after the disaster. The
      Impact of Event Scale (IES), the General Health Questionnaire (GHQ-28) and the
      Ways of Coping Checklists (WOC) were administered to the residents. RESULTS: On
      the whole, the results did not entirely support the hypothesis. The residents
      were found to have experienced some intrusive thoughts and avoidance behaviour
      but their mean scores were significantly lower than those of standardized
      samples. Thirty-five per cent scored at 4 or above on the GHQ-28. Traumatic
      stress was predicted by both emotion-focused and problem-focused coping
      strategies. CONCLUSION: Although community residents were not on the train or
      related to the dead or injured in any way, they could, after being exposed to a
      train disaster, manifest traumatic stress symptoms which had long-lasting
      effects. Such traumatic stress was found to be associated with coping strategies
      of community residents characterized by their efforts to manage or alter the
      source of stress, and by their efforts to regulate stressful emotions.

PMID- 11531737
TI  - An audit of medico-legal reports prepared for claims of psychiatric injury
      following motor vehicle accidents.
AB  - OBJECTIVE: The objective of this audit was to examine whether the content of
      medico-legal reports regarding psychiatric injury following motor vehicle
      accidents was influenced by the role of the report writers. METHOD: The audit
      consisted of a retrospective review, using a novel rating scale, of archived
      documents from 559 consecutively examined insurance claims following motor
      vehicle accidents in New South Wales. RESULTS: Treating practitioners wrote less
      complete reports than experts representing the plaintiff or defendant. Treating
      practitioners and plaintiffs' experts were more likely to diagnose posttraumatic
      stress disorder (PTSD) and depression, while defendants' experts were more likely
      to find no psychiatric disorder. Limitations of the study were that it was
      retrospective and examined report writing between 1989 and 1994. The
      completeness, rather than quality, of the medico-legal reports was measured.
      CONCLUSION: Further training and quality assurance procedures may improve medico
      legal report writing. Reform of the rules regulating the content of experts'
      reports may reduce the extent to which the role of the report writer influences
      their opinion.

PMID- 11531738
TI  - Effects of recurrences on some differences between bipolar II and unipolar
      depression.

PMID- 11531739
TI  - Antipsychotics and the law.

PMID- 11531740
TI  - Brain thyroid hormones, seasonal affective disorder, light therapy.

PMID- 11531741
TI  - Clozapine-risperidone combination in treatment-resistant schizophrenia.

PMID- 11531742
TI  - Psychotropic analgesic nitrous oxide (PAN) for hyperactivity.

PMID- 11531743
TI  - Increased risk of neutropaenia and agranulocytosis with sodium valproate used
      adjunctively with clozapine.

PMID- 11531744
TI  - Sertraline analysis in the plasma of breast-fed infants.

PMID- 11531745
TI  - Gender identity disorder as a rare manifestation of schizophrenia.

PMID- 11531746
TI  - The Australasian Radiation Oncology Lymphoma Group: an evolving role.

PMID- 11531747
TI  - Magnetic resonance imaging of the wrist in early rheumatoid arthritis: a
      pictorial essay.
AB  - This pictorial essay describes the changes seen in the wrist in early rheumatoid
      arthritis (RA) on MRI. Magnetic resonance imaging can demonstrate bone erosions,
      bone marrow signal changes, synovitis and tenosynovitis in early rheumatoid
      arthritis. Magnetic resonance imaging of the wrist can identify erosions in RA
      earlier than plain radiographs and can detect more erosions. Common sites include
      the capitate, lunate and scaphoid. Bone marrow signal changes occur frequently
      and are most common in the capitate, lunate and triquetrum. Synovial thickening
      and enhancement are clearly demonstrated with MRI and are most commonly seen in
      the radiocarpal joint (RCJ). Tenosynovitis can be seen in the wrist in more than
      half of patients presenting with RA. This most commonly involves the extensor
      carpi ulnaris tendon and is seen as sheath fluid, thickening and enhancement.

PMID- 11531748
TI  - Giant cell tumour of the tendon sheath of the hand: a pictorial essay.
AB  - Giant cell tumour of the tendon sheath is a soft tissue mass found occasionally
      in the hand. Its diagnosis can be readily made preoperatively if the
      characteristic MRI features are appreciated. This pictorial essay demonstrates
      and describes the imaging findings correlated with histopathological findings in
      a group of patients with proven giant cell tumour of the tendon sheath.

PMID- 11531749
TI  - Post-traumatic lumbar nerve root avulsion.
AB  - Lumbar nerve root avulsion is a rarely seen clinical entity that may complicate
      major trauma. The majority of previously reported cases have associated pelvic or
      lumbar vertebral fractures. Two cases of traumatic pseudomeningoceles at the
      lumbar level with associated avulsions of the lumbar nerve roots are presented.
      Both patients were involved in high velocity motor vehicle accidents. Case 1 had
      associated pelvic fractures but no spinal fractures and, interestingly, case 2
      had no fractures of the spine or pelvis. The value of MRI in making the diagnosis
      is demonstrated.

PMID- 11531750
TI  - Randomized prospective comparison of non-contrast enhanced helical computed
      tomography and intravenous urography in the diagnosis of acute ureteric colic.
AB  - Non-contrast enhanced helical CT has become an accepted technique for evaluating
      acute ureteric colic. The results of a randomized prospective comparison of the
      accuracy, cost and radiation dose of CT and intravenous urography (IVU) are
      presented. All patients presenting to the Emergency Department with symptoms and
      signs suggestive of ureteric colic over a 16-month period (n = 242) were
      randomized to CT or IVU. Follow up was obtained for 228 patients (94%), with 14
      patients (6%) lost to follow up. One hundred and twenty-three patients (54%)
      underwent CT and 105 (46%) had an IVU. At follow up the sensitivity and
      specificity of CT were each 100%, while those of IVU were 99% and 100%,
      respectively. Computed tomography demonstrated seven of 26 (27%) potential
      alternative diagnoses, whereas IVU suggested one of 23 (4%). Estimates of the
      average effective dose were calculated for CT (4.95 mSv) and IVU (1.48 mSv, 95%
      confidence interval (CI) 0.7-2.27). Radiation dose and intravenous contrast
      material safety are discussed and the relative costs are considered. Computed
      tomography is as accurate as IVU in the diagnosis of acute ureteric colic. It
      confers certain major diagnostic benefits, and is a fast, well-tolerated
      technique. Its accompanying higher effective radiation dose is recognized.

PMID- 11531751
TI  - Computed tomography versus intravenous urography in diagnosis of acute flank pain
      from urolithiasis: a randomized study comparing imaging costs and radiation dose.
AB  - The equivalent sensitivity of non-contrast computed tomography (NCCT) and
      intravenous urography (IVU) in the diagnosis of suspected ureteric colic has been
      established. Approximately 50% of patients with suspected ureteric colic do not
      have a nephro-urological cause for pain. Because many such patients require
      further imaging studies, NCCT may obviate the need for these studies and, in so
      doing, be more cost effective and involve less overall radiation exposure. The
      present study compares the total imaging cost and radiation dose of NCCT versus
      IVU in the diagnosis of acute flank pain. Two hundred and twenty-four patients
      (157 men; mean age 45 years; age range 19-79 years) with suspected renal colic
      were randomized either to NCCT or IVU. The number of additional diagnostic
      imaging studies, cost (IVU A$136; CTU A$173), radiation exposure and imaging
      times were compared. Of 119 (53%) patients with renal obstruction, 105 had no
      nephro-urological causes of pain. For 21 (20%) of these patients an alternative
      diagnosis was made at the initial imaging, 10 of which were significant. Of 118
      IVU patients, 28 (24%) required 32 additional imaging tests to reach a diagnosis,
      whereas seven of 106 (6%) NCCT patients required seven additional imaging
      studies. The average total diagnostic imaging cost for the NCCT group was
      A$181.94 and A$175.46 for the IVU group (P < 0.43). Mean radiation dose to
      diagnosis was 5.00 mSv (NCCT) versus 3.50 mSv (IVU) (P < 0.001). Mean imaging
      time was 30 min (NCCT) versus 75 min (IVU) (P < 0.001). Diagnostic imaging costs
      were remarkably similar. Although NCCT involves a higher radiation dose than IVU,
      its advantages of faster diagnosis, the avoidance of additional diagnostic
      imaging tests and its ability to diagnose other causes makes it the study of
      choice for acute flank pain at Christchurch Hospital.

PMID- 11531752
TI  - In vitro study of relationship between signal intensity and gadolinium-DTPA
      concentration at high magnetic field strength.
AB  - Although gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA) has been used
      as a contrast material in MRI, it is known that the contrast enhancement effect
      is not uniform for high concentrations of Gd-DTPA. In order to evaluate the
      proper pulse sequences for dynamic MRI in aqueous solutions of Gd-DTPA, blood
      samples and melanoma cells, the signal intensity for several concentrations of Gd
      DTPA were measured under inversion recovery (T1-weighted) at high magnetic field
      strength (7.0 Tesla). For aqueous solutions of Gd-DTPA, signal intensity
      correlated linearly with the concentration of Gd-DTPA between 0 mmol/L and 4
      mmol/L. Using blood and melanoma cells, signal intensity correlated non-linearly
      with the concentration of Gd-DTPA between 0 mmol/L and 1.5 mmol/L. For
      concentrations of more than 4 mmol/L in aqueous solutions of Gd-DTPA, 1 mmol/L in
      blood and 1.5 mmol/L in melanoma, signal intensity decreased with increased Gd
      DTPA concentration.

PMID- 11531753
TI  - Lace-like enhancement pattern of osteosarcoma of rib and liver metastasis in CT
      scans.
AB  - The rib is an uncommon site of osteosarcoma. With the use of adjuvant
      chemotherapy and aggressive surgical resection of the metastatic pulmonary
      lesions, extrapulmonary metastases are becoming more clinically evident. Primary
      rib osteosarcoma with extrapulmonary metastasis is exceedingly rare. A case is
      reported, showing that the pattern of metastasis of rib osteosarcoma is similar
      to that of primary bone osteosarcoma. The liver metastasis occurred after
      resection of the metastatic pulmonary lesions. A CT scan of the primary rib
      lesion and liver metastasis both showed a lace-like enhancement pattern, its
      histological appearance corresponding with neoplastic osteoid. With the
      increasing use of CT abdomen for localization of extrapulmonary metastases, lace
      like enhancement may be seen more readily in the future.

PMID- 11531754
TI  - Measurement of the transverse cerebellar diameter in preterm neonates and its use
      in assessment of gestational age.
AB  - This study aims to confirm the relationship between gestational age (GA) and
      transverse cerebellar diameter (TCD), to define the prediction of GA by TCD, and
      assess the reliability of TCD measurements. Infants were included in the study if
      they had a routine cranial ultrasound scan by day 3, and the TCD was measured.
      Infants were excluded from the study if the GA was not known, if there was any
      cranio-spinal malformation or grade 3 or 4 intraventricular haemorrhage (IVH).
      The GA assessment was an early pregnancy scan or certain dates. Cranial
      ultrasound scans were done with a LOGIQ 500 scanner (GE Medical Systems,
      Waukesha, WI, USA) with a 7 MHz curvilinear sector probe (GE LOGIQ-C721; GE
      Medical Systems). The posterior fossa was scanned using the asterion as the
      acoustic window with the TCD measured in the coronal plane. Intra- and
      interobserver reliability were assessed. A total of 221 infants of known GA had
      their TCD measured. The linear regression for GA versus TCD is: GA(weeks) =
      (0.470 x TCD(millimetres)) + 13.162 (r = 0.89, r(2) = 0.79, P < 0.001). The 95%
      confidence interval predicts GA to +/- 2.33 weeks for a given TCD. Intra- and
      interobserver intraclass correlation coefficients are 0.98 and 0.99,
      respectively. Transverse cerebellar diameter correlates closely with GA and
      predicts GA to +/- 2.33 weeks. Measurements of TCD have excellent
      reproducibility.

PMID- 11531755
TI  - Radiology interventions in patients receiving low molecular weight heparin:
      timing is critical.
AB  - Recent advances in diagnosis and treatment of venous thromboembolism have been
      associated with increasing use of low molecular weight heparins (LMWH) for
      treatment and prophylaxis of this disease. Despite this trend for more widespread
      use of LMWH, little is known of their safety in patients undergoing radiology
      interventions. Differences between LMWH and unfractionated heparin and the
      implications of these differences on use of LMWH in the setting of radiological
      interventions are outlined.

PMID- 11531756
TI  - In the case of the fabella a comparison view of the other knee is unlikely to be
      helpful.
AB  - The fabella is a common normal ossicle lying behind the knee. An experienced
      observer is unlikely to consider it to be an abnormality but, if there is
      uncertainty in the mind of the referring clinician, a comparison view of the
      other knee might be requested. This would be a useful decision if the bone in
      question was present on the other side in close to 100% of people. The incidence
      of the fabella was studied in the local population and it was found that it was
      bilateral in only 63% of people. This percentage is lower than that reported
      elsewhere (81-85%).1-4 Therefore, there was no reason to X-ray the opposite side
      to confirm that the ossicle in question was a fabella. If the local incidence of
      fabella had been a little lower, say 50%, it would have meant that tossing a coin
      would have been just as reliable as a "comparison view". Therefore, in case of
      doubt, the best advice seems to be to refresh the memory by consulting a
      reference book of normal variants and to take comparison views sparingly.

PMID- 11531757
TI  - Tandem lesions of the carotid circulation: combined extracranial endarterectomy
      and intracranial transluminal angioplasty.
AB  - A case series is presented demonstrating a unique approach to the treatment of
      tandem atherosclerotic lesions of the internal carotid artery. Between 1994 and
      1999 eight patients with tandem lesions of the internal carotid artery were
      treated by combined carotid endarterectomy for the proximal lesion and
      intraoperative angioplasty of the distal intracranial lesion via the carotid
      arteriotomy. The success and complication rates were evaluated. A 100% technical
      success rate was achieved with one post procedural complication by ipsilateral
      stroke within 24 h. The advantages of this technique include the treatment of
      tandem lesions by the one procedure, improved transluminal access to the
      intracranial lesion and the ability to reduce the risk of embolism by flow
      control during balloon inflation.

PMID- 11531758
TI  - Management of localized low-grade follicular lymphomas.
AB  - Long-term follow-up data from Stanford and other centres suggest that 40-50% of
      patients with clinical stages I and II follicular low-grade lymphoma can be cured
      by radiotherapy (RT). Relapse generally occurs outside radiation fields and most
      relapsed patients ultimately die from lymphoma. No randomized data exist to
      support adjuvant chemotherapy but only one trial of low-intensity chemotherapy
      was sufficiently powerful to address the question. Nevertheless, data from a
      large phase-II study from MD Anderson suggest that combined chemotherapy and RT
      can produce progression-free survival results that are far superior to historical
      series, with survival at 10 years to be approximately 20% superior to radiation
      alone. These results have encouraged the development of a joint phase III study
      by the Trans Tasman Radiation Oncology Group (TROG) and the Australasian
      Leukaemia and Lymphoma Group (ALLG) in which patients with clinical stage I/II
      follicular lymphoma are randomized to involved field RT with or without six
      cycles of cytotoxic chemotherapy. In an era of rapid development in immunological
      and molecular therapies the potential for improved results with new combinations
      of more established treatment modalities should not be forgotten. This report
      reviews the literature on the management of localized low-grade lymphoma and
      discusses the rationale for the TROG/ALLG study, which began recruitment in early
      2000.

PMID- 11531759
TI  - Inflammatory pseudotumour of the liver.
AB  - A case of inflammatory pseudotumour of the liver is presented. The clinical,
      radiological and pathological findings are described and a brief discussion of
      this rare but important condition is presented.

PMID- 11531760
TI  - Central nervous system aspergillus infection complicating renal transplantation.
AB  - A case of catastrophic intracerebral haemorrhage secondary to aspergillus
      infection in an immunocompromised renal transplant patient is presented. The
      pathological features and related images are described and the radiology of CNS
      aspergillus infection is reviewed.

PMID- 11531761
TI  - Lhermitte-Duclos disease associated with Cowden's syndrome: case report and
      literature review.
AB  - Lhermitte-Duclos disease (LDD) is a rare entity that may occur in the setting of
      Cowden's syndrome (CS). Accurate preoperative diagnosis can be made on the
      characteristic CT and MR appearances, thereby obviating the need for biopsy. It
      is important to be aware of the link between LDD and CS so that appropriate
      genetic counselling and tumour surveillance can be undertaken.

PMID- 11531762
TI  - Focal myositis.
AB  - Focal myositis is a rare, benign focal inflammation of muscle. The lesion often
      presents as a mass that may be mistaken for a soft tissue sarcoma. This report
      describes the MRI and histopathological features of a case and illustrates how
      the diagnosis may be suspected on the basis of the MR findings.

PMID- 11531763
TI  - Haemangiopericytoma of the trigeminal nerve.
AB  - A 41-year-old man presented with a 4-year history of progressive right-sided
      diplopia on lateral gaze and right nasolabial paraesthesia. A CT revealed minor
      bone erosion of Meckel's cave and of the right petrous apex by a uniformly
      enhancing lesion at the base of the skull. Magnetic resonance imaging on three
      occasions over 2 years showed tumour, measuring 4 cm in diameter, with features
      suggestive of a trigeminal neuroma. At surgery the lesion had the macroscopic
      appearance of a giant schwannoma. Histopathological findings were that of a
      meningeal haemangiopericytoma (HPC) of the trigeminal nerve. Intracranial HPC are
      rare and aggressive tumours of the central nervous system. They usually arise
      from the falx, tentorium and dural sinuses. The present case is unique as it
      originates from a cranial nerve.

PMID- 11531765
TI  - Methanol intoxication with bilateral basal ganglia infarct.
AB  - Methanol is a toxic agent that affects the central nervous system, especially the
      optic nerves and basal ganglia. Symmetrical hypodense lesions in the basal
      ganglia, which can be demonstrated by CT or MRI, is accepted as the most
      characteristic radiological feature of the disease. A case of a patient with
      bilateral putaminal hypodense infarcts due to methanol intoxication is presented.

PMID- 11531764
TI  - Fetus in fetu. Rare cause of a lump in an adult's abdomen.
AB  - Fetus in fetu is a rare entity. The patient usually presents in childhood. A case
      in which the patient presented in adulthood, with a lump in the abdomen, is
      reported. Computed tomography findings were diagnostic of this condition and a
      prospective diagnosis could be made. Computed tomography also helped to
      differentiate it from mature teratoma.

PMID- 11531766
TI  - Odontoid fracture following an epileptic seizure.
AB  - Fractures of the thoracic and lumber spine are well recognized following an
      epileptic seizure. Fractures of the cervical spine are not. The rare occurrence
      of a displaced odontoid fracture type 2, secondary to a grand mal seizure is
      presented. To our knowledge, this association has not been described previously
      in the English literature.

PMID- 11531767
TI  - Malrotation of the bowel resulting in a left-sided caecal carcinoma presenting as
      a palpable intrahernial mass.
AB  - An 86-year-old woman presented with a large left-sided intrahernial mass, which
      was shown on CT to represent an abnormally located caecal tumour. An underlying
      bowel malrotation was also found explaining the left-sided nature of the mass.

PMID- 11531768
TI  - Tuberculous biliary strictures: uncommon cause of obstructive jaundice.
AB  - Tuberculous biliary stricture is a very rare cause of obstructive jaundice. A
      case of a man who had had pulmonary tuberculosis 20 years ago is reported. He now
      presented with obstructive jaundice due to multiple strictures just below the
      confluence of the hepatic ducts and in the right hepatic duct. At surgery these
      turned out to be tuberculous in origin. There was also tuberculous involvement of
      the gall bladder and cystic duct. The commonest differential diagnosis in such
      cases is cholangiocarcinoma (as in the present case). Imaging helps in defining
      the extent of bile duct obstruction. Suspicion of the disease and establishing a
      tissue diagnosis is very important in treating this potentially curable
      condition, especially with the worldwide resurgence of tuberculosis.

PMID- 11531769
TI  - Choroid plexus carcinoma in an adult.
AB  - Choroid plexus carcinomas are rare in adults. They can behave aggressively and
      their optimal management is uncertain. An adult patient with choroid plexus
      carcinoma who was treated with an incomplete surgical resection and postoperative
      radiotherapy is reported. Despite an identifiable local response to radiotherapy,
      disease progression resulted in death 4 years after presentation. This report
      reviews the current literature and discusses the management issues regarding this
      uncommon adult malignancy.

PMID- 11531770
TI  - Primary spinal epidural extraosseous Ewing's sarcoma: report of five cases and
      literature review.
AB  - Ewing's sarcoma is the most common malignant bone tumour occurring in children
      and adolescents and exists in two different clinicopathological entities: osseous
      Ewing's sarcoma (OES) and extraosseous Ewing's sarcoma (EES). Five cases of
      primary epidural EES are described, which presented with non-specific symptoms
      leading to a long diagnostic delay. The median age at diagnosis was 22 years
      (range 13-36 years). The median diagnostic delay was 3 months. All patients had
      one or more neurological deficits. All underwent surgical exploration with a
      laminectomy and partial resection followed by adjuvant radiotherapy to a dose of
      46-50 Gy and chemotherapy with VAC (vincristine, adriamycin and cyclophosphamide)
      alternating with ICE (ifosphamide, cisplatin and etoposide) for at least six
      cycles. The mean follow-up period is 21.2 months (range 11-32 months). Four of
      the five patients achieved a complete remission and are disease free at the time
      of writing this report. Two patients have a residual neurological deficit--both
      having presented with long history of neurological deficit. Primary spinal
      epidural EES should be suspected whenever young patients present with back pain
      and/or radicular pain, have abnormal neurology and an extradural mass is
      demonstrated on MRI. Surgical excision followed by adjuvant radiotherapy (50 Gy)
      and combination chemotherapy (VAC alternating with ICE) achieved local and
      systemic control in these patients. A greater number of patients and longer
      follow up are required to evolve a generally accepted treatment policy for this
      aggressive but potentially curable malignancy.

PMID- 11531771
TI  - Carcinoma breast metastatic to the hand and the foot.
AB  - Metastases to the peripheral bones of the extremities are rare. Such lesions are
      often diagnosed as inflammatory or infective in nature. We present a report of a
      case of simultaneous involvement of the peripheral bones of the extremities--the
      talus and the thumb of the left hand--with a brief review of pathophysiology and
      management.

PMID- 11531772
TI  - Intra-arterial embolization of lumbar artery pseudoaneurysm following
      percutaneous nephrolithotomy.
AB  - The management of a patient with haematuria following percutaneous
      nephrolithotomy is described. The patient underwent renal angiography to assess
      the cause of bleeding. A pseudoaneurysm arising from first left lumbar artery was
      incidentally discovered, which was then successfully embolized using an
      indigenously fabricated metallic coil and gel foam particles in the same sitting.

PMID- 11531773
TI  - Pneumothorax preceding pulmonary blastoma in a child.
AB  - Serial plain radiographic, ultrasound and CT findings of an unusual case of
      pulmonary blastoma are described with a review of the literature.

PMID- 11531774
TI  - Spongiform leucoencephalopathy following intravenous heroin abuse: radiological
      and histopathological findings.
AB  - A case of spongiform leucoencephalopathy in a known intravenous heroin abuser is
      presented. To our knowledge, this is the only case of heroin-related spongiform
      leucoencephalopathy reported in Australia. The relationship to intravenous rather
      than inhaled heroin is particularly unusual with only one other possible case
      documented in the literature. The imaging and histopathological findings are
      described.

PMID- 11531775
TI  - RE: The importance of pathology.

PMID- 11531776
TI  - The importance of pathology revisited.

PMID- 11531777
TI  - Massive L5/S1 disc protrusion: subtle CT signs.

PMID- 11531778
TI  - The value of reverse transcription-polymerase chain reaction in malignant
      melanoma.

PMID- 11531779
TI  - Detection of melanoma cells in sentinel lymph nodes, bone marrow and peripheral
      blood by a reverse transcription-polymerase chain reaction assay in patients with
      primary cutaneous melanoma: association with Breslow's tumour thickness.
AB  - BACKGROUND: Tyrosinase reverse transcription-polymerase chain reaction (RT-PCR)
      has been shown to be highly sensitive in detecting tumour cells in melanoma
      patients. OBJECTIVE: To assess whether the detection of minimal residual disease
      by RT-PCR is improved by concomitant analysis of sentinel lymph nodes (SLNs),
      bone marrow (BM) and peripheral blood (PB) in patients with primary melanoma.
      METHODS: Thirty-five SLNs, 41 BM samples and 26 PB specimens from 26 patients
      with primary cutaneous melanoma (tumour thickness > or = 0.75 mm) were examined
      by nested RT-PCR for tyrosinase and Melan-A. SLNs and BM samples were also
      analysed by histopathology. RT-PCR findings were related to tumour thickness of
      the primary melanoma. RESULTS: Overall, melanoma cells were detected by RT-PCR in
      13 of 26 patients (50%). Seven patients had positive RT-PCR results in their SLNs
      (27%), including all patients (n = 4) with histologically positive SLNs, two
      patients had positive findings in their BM exclusively detected by RT-PCR (8%)
      and six patients in PB (23%). The presence of tumour cells detected by RT-PCR in
      SLNs was not related to the presence of melanoma cells in BM and/or PB. The
      incidence of RT-PCR-positive SLNs was significantly associated with greater
      tumour thickness (P = 0.004). Both patients with positive RT-PCR findings in
      their BM had a large tumour thickness (> or = 2 mm). No association between
      positive RT-PCR findings in PB and greater tumour thickness was observed.
      CONCLUSIONS: RT-PCR-positive SLNs were strongly associated with greater tumour
      thickness, underlining the prognostic significance of SLN positivity. Similar to
      certain epithelial malignancies, molecular investigation of the BM might provide
      complementary prognostic information in the early stages of melanoma. In
      contrast, no association between positive RT-PCR results in PB and increasing
      tumour thickness was found, implying that RT-PCR findings in PB are of doubtful
      clinical relevance in primary melanoma.

PMID- 11531780
TI  - Prognostic immunohistochemical markers of primary human melanomas.
AB  - BACKGROUND: Several clinical and histological factors of primary melanomas
      comprise a relatively large quantity of prognostic information. OBJECTIVE: To
      find immunohistochemical markers that can improve the prognostic accuracy
      achieved by factors that are available without extra laboratory work, i.e.
      mitotic rate, tumour thickness, ulceration, localization, gender and age.
      METHODS: Immunohistochemical markers were determined on frozen sections.
      Univariate and multivariate Cox regression analyses were performed after 5-10
      years follow-up. RESULTS: Seven immunohistochemical markers were related to
      disease-free and overall survival in univariate Cox regression analysis: Ki-67,
      human leucocyte antigen (HLA) -DQ, HLA-DP, Muc 18, A-10-33, transferrin receptor,
      and H-2-8-10. Only Ki-67 (n = 399) and HLA-DQ (n = 452) retained prognostic
      significance when evaluated in multivariate analyses in several models together
      with tumour thickness alone and with tumour thickness, gender, mitotic rate, age,
      localization and ulceration. CONCLUSIONS: Ki-67 and HLA-DQ may be useful for risk
      assessments in primary melanomas.

PMID- 11531782
TI  - Increased deposition of fibulin-2 in solar elastosis and its colocalization with
      elastic fibres.
AB  - BACKGROUND: Fibulin-2 is a 195-kDa protein belonging to a novel family of
      extracellular matrix proteins that might be involved in microfibril and elastic
      fibre organization. OBJECTIVES: To determine the localization of fibulin-2 in
      relation to elastic fibres in normal skin and in solar elastosis characterized by
      increased elastotic material in the papillary dermis. METHODS: The expression and
      synthesis of fibulin-2 was investigated by means of in situ hybridization,
      immunohistochemistry and Western blot analysis in normal and photoaged skin.
      RESULTS: Immunohistochemistry and elastic tissue staining revealed that fibulin-2
      deposition mainly colocalized with microfibrils and elastin fibres, with a marked
      staining of elastotic material in solar elastosis. Western blot analysis
      demonstrated that in photoaged skin fibulin-2 showed the same electrophoretic
      mobility as in sun-protected skin. However, in actinic elastosis the amount of
      fibulin-2 was significantly higher. In addition, smaller degradation products
      were detectable, presumably reflecting increased proteinase activity in
      photodamaged skin. CONCLUSIONS: This study shows that deposition of fibulin-2 and
      elastin is highly co-ordinated, indicating that this protein plays an important
      role in elastic fibre and microfibril formation in normal and actinically damaged
      skin.

PMID- 11531781
TI  - Loss of beta-catenin expression associated with disease progression in malignant
      melanoma.
AB  - BACKGROUND: beta-catenin plays a crucial role in the function of cell adhesion
      molecules and also participates in growth regulatory signalling pathways that may
      be involved in malignant transformation. OBJECTIVES: To examine beta-catenin
      expression in lesions of melanocytic origin for associations with
      clinicopathological markers of disease progression and for its significance as a
      predictor of disease recurrence and prognosis. METHODS: beta-catenin expression
      was examined by immunoperoxidase staining in 50 melanocytic naevi and 91 primary
      and 50 metastatic melanomas. RESULTS: beta-catenin was expressed in 96% of
      melanocytic naevi, in 94% and 65%, respectively, of radial and vertical growth
      phase primary melanomas, and in 38% of metastatic melanomas. Benign and malignant
      melanocytic lesions had distinct patterns of beta-catenin localization. Most
      lesions expressing beta-catenin exhibited cytoplasmic staining; however, over 40%
      of benign lesions also displayed nuclear staining, which was present only in 10%
      of primary and 15% of metastatic melanomas. Absent or weak expression of beta
      catenin in primary melanomas was associated with several markers of disease
      progression, including tumour thickness and presence of lymph node metastases. A
      similar but not statistically significant trend was observed for the association
      of beta-catenin expression with disease recurrence and prognosis. CONCLUSIONS:
      These results suggest that loss or downregulation of beta-catenin expression in
      melanoma cells plays a significant role in progression of the disease.

PMID- 11531783
TI  - Patterns of basal cell keratin 14 expression in Bowen's disease: a possible
      marker for tumour progression.
AB  - BACKGROUND: Bowen's disease is a well-established in situ malignancy of the
      epidermis. The keratin expression in Bowen's disease has been studied in many
      reports. However, the patterns of keratin (K) 14 expression in each case have not
      been closely examined. OBJECTIVES: To investigate if the pattern of expression of
      K14 has a relationship with tumour progression, we analysed the expression
      patterns of K14 in relation to the nature of tumour cells, comparing tumour cells
      in direct contact with the dermis, tumour cells separated from the dermis, and
      tumour cells invading into the dermis. METHODS: Twenty-seven tissue sections from
      22 patients were stained with anti-K14 antibody, as well as with antilaminin and
      periodic acid-Schiff (PAS) staining to evaluate the conditions of the basement
      membrane. Staining patterns of K10 and integrin beta1, and their relationships
      with proliferating cell nuclear antigen (PCNA) and Ki-67 staining patterns, were
      also examined. RESULTS: Tumour cells with no, or with obscured, basement
      membranes always showed positive staining for K14, while those with continuous
      (intact) basement membranes usually did not. Of 10 sections showing dermal
      involvement of Bowen's disease, five were K14 positive and five were K14
      negative. All of these K14-positive sections with dermal involvement showed
      negative or obscured laminin and PAS staining. Most of the sections having K14
      negative tumour cells with dermal involvement showed K14-positive lining cells
      with continuous staining with laminin and PAS-positive basement membranes. K10
      was reciprocally expressed with K14 in most of the sections. Integrin beta1 was
      expressed in the basal layers of non-tumour epidermal cells, but not in tumour
      cells. Ki-67 and PCNA were expressed at high frequencies in tumour cells, clearly
      demarcating tumour cells from non-tumour cells. CONCLUSIONS: Tumour cells
      separated from the dermis by lining cells were K14 negative with PAS- and laminin
      positive basement membranes around them; tumour cells without lining cells were
      K14 positive with or without continuous basement membranes. K14 expression may be
      a marker of tumour progression in Bowen's disease.

PMID- 11531784
TI  - A candidate gene analysis of three related photosensitivity disorders: cutaneous
      lupus erythematosus, polymorphic light eruption and actinic prurigo.
AB  - BACKGROUND: Polymorphic light eruption (PLE) is a common inherited
      photosensitivity disorder, which may predispose to several related but distinct
      conditions, including subacute cutaneous lupus erythematosus (SCLE), discoid
      lupus erythematosus (DLE) and actinic prurigo (AP). OBJECTIVES: To examine
      specific candidate genes for shared susceptibility alleles between these related
      phenotypes. METHODS: Eighty-five caucasian patients with annular SCLE or DLE were
      recruited, in addition to 102 first-degree relatives. The prevalence of PLE in
      both the patient and relative groups was determined by detailed interview and
      clinical examination. Eighty-five patients with pure PLE and 59 patients with AP
      were also recruited. Candidate genes were analysed by typing of single nucleotide
      polymorphisms of IL10 (-1082 G/A and -819 C/T), FCGR2A (131 R/H), SELE (128 S/R),
      ICAM1 (241 G/R and 469 E/K), IL1A (+ 4845 G/T), IL1B (-511 C/T and + 3954 C/T),
      IL1RN (+ 2018 T/C) and TNF (-308 G/A) using polymerase chain reaction (PCR) with
      sequence-specific primers and 5'-nuclease PCR. RESULTS: A significant association
      was found between SCLE and the rare TNF -308 A allele when compared with patients
      with DLE (P = 0.043), PLE (P = 0.001), AP (P < 0.001) and healthy controls (P <
      0.001). However, there was strong linkage disequilibrium between TNF -308 A and
      the HLA A*01, B*08, DRB1*0301 haplotype. A negative association was also found
      between SCLE and the IL1B + 3954 T allele (P = 0.039), but the significance was
      lost on correction for multiple testing. CONCLUSIONS: We have demonstrated the
      association of SCLE with the rare TNF -308 A allele, which may be pathogenic or,
      alternatively, a marker allele for the extended HLA A*01, B*08, DRB1*0301
      haplotype that is associated with a number of autoimmune conditions. Although
      many of the other loci that we chose failed to demonstrate an association, a
      candidate gene approach remains the most logical one, and the most likely to
      yield positive results in the future.

PMID- 11531785
TI  - Effects of solar-simulated radiation dose fractionation on CD1a+ Langerhans cells
      and CD11b+ macrophages in human skin.
AB  - BACKGROUND: There are few human studies investigating the immunosuppressive
      effects of exposure to solar-simulated radiation (SSR) and its relationship with
      sunburn/erythema, and few comparative data on the importance of SSR exposure
      regimens. OBJECTIVES: To evaluate whether SSR-induced erythema is a reliable end
      point for assessing damage to antigen-presenting cells (APCs) in human skin.
      METHODS: We compared the relationship between SSR-induced erythema and
      alterations in epidermal CD1a+ Langerhans cells (LCs) and CD11b+ macrophages in
      human volunteers after single exposures to 0, 0.5, 1, 2 or 3 minimal erythema
      doses (MED). We also investigated whether SSR exposure leads to an accumulation
      or accommodation of the same end-points by comparing the effects of a relatively
      low cumulative SSR dose (3 MED) given in varying daily dose fractions (4 x 0.75
      MED, 2 x 1.5 MED and 1 x 3 MED). RESULTS: Single SSR exposures induced a dose
      dependent increase in erythema. CD1a+ LCs remaining in the irradiated epidermis
      showed a dose-dependent increase in cell size and altered morphology. Significant
      depletion of CD1a+ LCs and presence of CD11b+ macrophages only occurred in sites
      irradiated with 2 MED and 3 MED. Dose fractionation had no effect on the final
      erythemal response but the 4 x 0.75 MED and 1 x 3 MED protocols were better
      tolerated than 2 x 1.5 MED for alterations in CD1a+ LC and CD11b+ cell numbers.
      In contrast, dose fractionation protected against alterations in CD1a+ LC
      morphology or cell size. CONCLUSIONS: We found that erythema is a poor indicator
      of alterations in epidermal APCs and that dose fractionation is an important
      parameter in the immunological effects of ultraviolet radiation.

PMID- 11531786
TI  - Contrasting patterns of streptococcal superantigen-induced T-cell proliferation
      in guttate vs. chronic plaque psoriasis.
AB  - BACKGROUND: Streptococcal infection is strongly associated with guttate psoriasis
      (GP) and may also exacerbate chronic plaque psoriasis (CPP), possibly through the
      release of superantigenic toxins. OBJECTIVES: To investigate superantigen-induced
      generation of cutaneous lymphocyte associated antigen (CLA) -positive lymphocytes
      in GP compared with CPP. METHODS: Peripheral blood lymphocyte (PBL) expression of
      CLA and T-cell receptor Vbeta chain was assessed in patients with CPP and with
      active and resolved GP. Expression of superantigen-reactive Vbeta families was
      compared with in vitro superantigen-induced peripheral blood mononuclear cell
      (PBMC) proliferation. RESULTS: Peripheral blood mononuclear cells from patients
      with active GP showed a twofold increased proliferation after stimulation with
      streptococcal pyogenic toxins A and streptococcal pyogenic toxins C compared with
      controls (P < 0.01), whereas the response to the staphylococcal toxins and
      mitogenic stimulation was the same in all groups. Peripheral blood lymphocytes
      (PBL) from patients with active GP showed increased use of the superantigen
      reactive families Vbeta2 (P < 0.01) and Vbeta17 (P < 0.05), which was not evident
      in the other patient groups or controls. This pattern of Vbeta expression was
      only observed in CLA-positive T cells. Furthermore, there was a positive
      correlation between Vbeta2 expression and enhanced proliferation after
      stimulation with SPEA (r = 0.82, P < 0.01) and SPEC (r = 0.74, P < 0.05) in
      active GP. CONCLUSIONS: This study supports the concept that streptococcal
      infection precipitates acute GP at least in part through superantigen driven
      generation of Vbeta-restricted CLA-positive skin homing lymphocytes, whereas we
      could find no evidence for a similar mechanism occurring in the maintenance of
      stable CPP.

PMID- 11531787
TI  - Epidermal proliferative response induced by sodium dodecyl sulphate varies with
      environmental humidity.
AB  - BACKGROUND: Previous studies have suggested that susceptibility of skin to
      external agents increases in the dry winter season. OBJECTIVES: To test the
      hypothesis that environmental humidity affects skin sensitivity to irritants.
      METHODS: The epidermal hyperplasia induced by sodium dodecyl sulphate (SDS) under
      various humidity conditions was evaluated on the skin of hairless mice. RESULTS:
      Mice kept under low humidity for 2 days showed more obvious epidermal
      proliferation 24 h after topical application of SDS than those kept under high or
      normal humidity for 2 days. In contrast, mice kept under high humidity for 2
      weeks showed more obvious epidermal proliferation 24 h after topical application
      of SDS than those kept under low or normal humidity. The transepidermal water
      loss was altered significantly in the animals kept under high humidity for 2
      weeks, although it was not altered during the first 7 days under either low or
      high humidity. CONCLUSIONS: These results suggest that environmental humidity
      influences the sensitivity of skin to topical application of SDS and that
      increased sensitivity is not always associated with alteration of the water
      impermeability of the stratum corneum.

PMID- 11531788
TI  - Sensitive skin: an epidemiological study.
AB  - BACKGROUND: There is a growing awareness that some individuals exhibit heightened
      skin sensitivity, particularly on the face, and have a high incidence of adverse
      reactions to cosmetics and toiletries. OBJECTIVES: To carry out an
      epidemiological study to assess the prevalence of sensitive skin and cosmetic
      related adverse events in a U.K. population, and to examine possible factors that
      may be associated with sensitive skin. METHODS: Self-assessment questionnaires
      were sent out to 3300 women and 500 men, randomly selected, who were over the age
      of 18 years and lived within a 10-mile radius of High Wycombe (Bucks.). Fifty non
      responder women were also questioned by telephone to ensure that the postal
      responders were representative of the population as a whole. RESULTS: The
      response rates were 62% for women and 52% for men, with the incidence of self
      reported skin sensitivity being 51.4% and 38.2%, respectively. Ten per cent of
      women and 5.8% of men described themselves as having very sensitive skin. Fifty
      seven per cent of women and 31.4% of men had experienced an adverse reaction to a
      personal product at some stage in their lives, with 23% of women and 13.8% of men
      having had a problem in the last 12 months. Among the women, symptoms of cosmetic
      induced subjective sensory skin discomfort (burning, stinging, itching etc.)
      occurred more commonly in the sensitive skin cohort (53%) than in those who
      regarded themselves as non-sensitive (17%). An atopic diathesis in women did not
      appear to be a predictive factor for sensitive skin, the incidence of self
      perceived sensitive skin being equivalent for atopics (49%) and non-atopics
      (51%). Furthermore, some 34% of atopic women described themselves as being non
      sensitive. Nevertheless, the incidence of atopy was higher among the women in the
      sensitive skin group (49%) than among those in the non-sensitive group (27%). Dry
      skin and a predilection for blushing/flushing were associated factors for
      sensitive skin. CONCLUSIONS: Our survey indicates that sensitive facial skin is a
      common problem for women and men in the U.K. and points to the need for the
      development of personal products designed for this skin phenotype.

PMID- 11531789
TI  - Ointment is evenly spread on the skin, in contrast to creams and solutions.
AB  - BACKGROUND: The efficacy of topical therapy depends on the patient spreading the
      topical drug in an even layer to give a standard dose. Ointments are believed to
      be more effective than creams and solutions. OBJECTIVES: To compare the
      application and spreading of four different pharmaceutical vehicles. METHODS:
      Twenty-nine healthy volunteers applied a fixed amount (0.1 g) of solution (S),
      ointment (O), cream (C) and low-viscosity cream (LVC) to the abdominal skin. Area
      of spread, skin surface lipids (dependent on formulation) and changes in skin
      surface temperature (cooling due to evaporation of formulation water/alcohol)
      were measured. RESULTS: Area of spread: O = C = LVC = S. Skin surface lipids: O >
      C > LVC > S. Difference in skin surface lipids between centre and periphery: O <
      C = LVC = S. Cooling: O < C = LVC < S. CONCLUSIONS: The four formulations were
      spread to similar areas. The ointment was spread evenly in the treated area while
      the other formulations were unevenly spread, with a lower dose in the periphery.
      Creams and solutions have disadvantages as vehicles, as rapid evaporation of
      formulation water/alcohol, measured as cooling, influences spread, resulting in
      an uneven topical dose within the treated area. In contrast, ointment is evenly
      spread and is thus a more appropriate formulation. Patients should be instructed
      to apply creams and solutions to multiple sites and to spread them quickly.

PMID- 11531790
TI  - The significance of fragrance mix, balsam of Peru, colophony and propolis as
      screening tools in the detection of fragrance allergy.
AB  - BACKGROUND: Patch testing to fragrances is an important step in the diagnosis of
      fragrance allergy. OBJECTIVES: To determine the usefulness of adding propolis to
      the European standard series to test for fragrance allergy. PATIENTS AND METHODS:
      A total of 2660 consecutive patients were patch tested with a standard patch test
      series; 747 suspected of fragrance allergy were tested further with a special
      fragrance series. RESULTS: The positive results to the standard series in 2660
      patients were: fragrance mix 243 (9.1%), Myroxylon Pereirae [balsam of Peru] 144
      (5.4%), colophony 32 (1.2%); these fragrance mixtures are used as screening
      substances for fragrance allergy in the European standard series. Propolis, also
      known as bee's glue, was also an important allergen in this locally revised
      standard series (n = 35, 1.3%). Positive reactions to the aforementioned
      allergens were associated significantly among each other (P < 0.01, chi2-test)
      and did not differ between the sexes. The primary locations of dermatitis in
      patients with a positive test to one or more fragrance allergens (n = 162) among
      those suspected of fragrance allergy (n = 747) were: face 46.9%, hands 23.5%,
      neck 17.9%, axillae 12.3%; 92 of the 747 patients suspected of fragrance allergy
      had positive skin tests to the special fragrance series comprising the eight
      constituents of the fragrance mix (most frequent: isoeugenol 5.4%, oakmoss
      absolute 5.0%, eugenol 2.5%) and 14 other fragrance allergens (most frequent:
      clove oil 1.6%, lemon grass oil 0.8%, cedar wood oil 0.7%). The additional value
      of propolis as another screening substance for fragrance allergy in these
      patients was low. The likelihood of a reaction to one or more of the extra
      fragrance allergens increased with the number of reactions to fragrance screening
      allergens in the standard series. CONCLUSIONS: The number of positive reactions
      to fragrance screening allergens in a standard patch test series may be used as a
      rule of thumb for predicting a positive outcome of a more detailed testing to
      fragrances. Propolis is an important allergen in its own right but its value as a
      screening substance for fragrance allergy is limited.

PMID- 11531791
TI  - Acne prevalence, knowledge about acne and psychological morbidity in mid
      adolescence: a community-based study.
AB  - BACKGROUND: Acne vulgaris is a distressing condition that affects the majority of
      adolescents, but its impact on mental health in this age group is poorly
      understood. OBJECTIVES: To determine the prevalence of acne, knowledge about acne
      and rates of help-seeking behaviour in English teenagers. It was hypothesized
      that presence of acne would be associated with higher rates of emotional and
      behavioural difficulties. METHODS: Three hundred and seventeen pupils (80%
      response rate) aged 14-16 years participated from a comprehensive school in
      Nottingham. An age-appropriate, validated measure of emotional well-being, the
      Strengths and Difficulties Questionnaire (SDQ), and an Acne Management
      Questionnaire were used to assess participants' psychological health, level of
      acne knowledge and help-seeking behaviour. Acne severity was by graded by visual
      facial examination using an adaptation of the Leeds Acne Grading Technique.
      RESULTS: There was a prevalence of acne in 50% of the study sample, with 11% of
      participants having moderate to severe acne (> 20 inflammatory lesions).
      Participants with definite acne (12+ lesions) (P < 0.01) and girls (P < 0.05) had
      higher levels of emotional and behavioural difficulties. Participants with acne
      were nearly twice as likely as those without acne to score in the
      abnormal/borderline range of the SDQ (32% vs. 20%; odds ratio 1.86, 95%
      confidence interval 1.03-3.34). Knowledge about the causes of acne was low (mean
      45%), and was unrelated to acne status. Fewer than a third of participants with
      definite acne had sought help from a doctor. CONCLUSIONS: Acne is a common
      disorder in English adolescents and appears to have a considerable impact on
      emotional health in this age group. Low levels of acne knowledge and poor acne
      management are concerns that could be amenable to a school-based education
      programme.

PMID- 11531792
TI  - The importance of serum creatine phosphokinase level in the early diagnosis, and
      as a prognostic factor, of Vibrio vulnificus infection.
AB  - BACKGROUND: Vibrio vulnificus infection causes rapidly progressive skin lesions
      and sepsis in compromised hosts with liver cirrhosis, and is often fatal. Early
      diagnosis and rapid treatment are important. OBJECTIVES: To clarify the
      characteristics of V. vulnificus infection that distinguish it from other
      cutaneous and soft-tissue bacterial infections and to confirm that serum creatine
      phosphokinase (CPK) levels are useful in early diagnosis, and are a prognostic
      factor for, V. vulnificus infection. METHODS: We analysed the clinical and
      laboratory findings (especially serum CPK levels) in eight patients with V.
      vulnificus infection who were treated at the Saga Medical School Hospital between
      January 1989 and December 1999. RESULTS: All eight patients had liver dysfunction
      and typical skin manifestations. Six had eaten raw seafood before onset. Seven
      patients had initial skin manifestations in their legs or feet and eventually
      died, despite prompt therapy in the intensive care unit. CPK levels of six of
      these seven patients were already elevated at their initial presentation. Only
      one patient, with skin manifestations solely on his left hand, showed and
      maintained a normal CPK level and survived. In 23 patients with cutaneous and
      soft-tissue infections (10 with necrotizing fasciitis, three with erysipelas, 10
      with cellulitis), only three patients with necrotizing fasciitis and
      streptococcal toxic shock syndrome (STSS) showed CPK elevation. CONCLUSIONS: A
      high level of serum CPK in cutaneous or soft-tissue bacterial infection is
      considered useful for an early diagnosis of V. vulnificus infection and STSS. A
      history of eating raw seafood, underlying liver disease and multiple lesions
      suggest a diagnosis of V. vulnificus infection, rather than STSS.

PMID- 11531793
TI  - Diagnostic impact and sensitivity of skin biopsies in Sneddon's syndrome. A
      report of 15 cases.
AB  - BACKGROUND: Sneddon's syndrome is defined as a combination of idiopathic livedo
      racemosa generalisata and symptoms of cerebrovascular defect. The disease usually
      starts with vascular symptoms in the epidermis, with neurological deficits
      becoming evident later. For this reason, histological examination of skin
      biopsies and determination of arteriolar occlusion is of particular importance
      for reliable categorization and early diagnosis. To date, these methods have been
      considered to be too insensitive. OBJECTIVES: To evaluate the sensitivity of skin
      biopsies in Sneddon's syndrome. METHODS: We took a total of five deep punch
      biopsies (4 mm) from different areas of the livedo (three from white and two from
      red areas) in 15 patients. Present knowledge of the pathogenic relationships and
      the particular anatomical features of the skin were taken into account. RESULTS:
      The method had a sensitivity of 27% with one biopsy, 53% with two biopsies and
      80% with three biopsies taken from white areas in all cases. CONCLUSIONS: Skin
      biopsies using the method presented achieved a high sensitivity, suggesting that
      the diagnosis in clinically suspected cases could be confirmed in the majority of
      cases with this technique.

PMID- 11531794
TI  - Treatment of focal hyperhidrosis with botulinum toxin type A: long-term follow-up
      in 61 patients.
AB  - BACKGROUND: The blocking action of botulinum toxin type A (BTX-A) on
      cholinergically innervated sweat glands has been used successfully to treat
      patients with focal hyperhidrosis. OBJECTIVES: To investigate the long-term
      efficacy and safety of intradermal injections of BTX-A. METHODS: We performed an
      open-label study in 61 patients treated over a period of 3 years for axillary or
      palmar hyperhidrosis. A total dose of 400 mU BTX-A (Dysport) was injected into
      both axillae or 460 mU BTX-A (Dysport) into both palms. The injections were
      repeated after relapse. Objective quantification of sweat production was
      performed using digitized ninhydrin-stained sheets. RESULTS: Four weeks after BTX
      A treatment the median reduction in sweat production was 71% compared with
      baseline (P < 0.001) in the axillary group and 42% (P = 0.005) in the palmar
      group. Subjective assessment of sweat production by the patients using a visual
      analogue scale (0, no sweating; 100, the most severe sweating) showed a
      significant reduction in both the axillary (P < 0.001) and palmar groups (P <
      0.001). Secondary disturbances due to focal hyperhidrosis interfering with daily
      activities were markedly improved in both groups. The median time interval
      between the sets of injections was 34 weeks for axillary hyperhidrosis and 25
      weeks for palmar hyperhidrosis. The treatment of palmar hyperhidrosis was
      complicated by transient but not disabling weakness of the small hand muscles in
      nine of 21 patients. CONCLUSIONS: Repeated intradermal injections of BTX-A in
      patients with axillary and palmar hyperhidrosis are as effective as first
      treatments.

PMID- 11531795
TI  - African hair growth parameters.
AB  - BACKGROUND: Hair growth parameters have been studied mostly in caucasian hair,
      whereas few data on African hair have been reported in the literature.
      OBJECTIVES: To evaluate hair growth characteristics of African volunteers born in
      Africa. METHODS: Thirty-eight young adults (19 women, 19 men, mean +/- SD age 27
      +/- 10 years), native of central and western Africa, took part in the study.
      Phototrichograms were performed in order to record three parameters of hair
      growth: hair density, telogen percentage and rate of growth. For each volunteer,
      three regions of the scalp, namely vertex, temporal and occipital areas, were
      assessed. RESULTS: Hair density varied from 90 to 290 hairs cm(-2), with higher
      counts on the vertex. No significant difference between men and women was
      recorded. Telogen percentage showed wide variations, from 2 to 46%, with higher
      levels on the temporal area and in men. The rate of growth fluctuated from 150 to
      363 microm day(-1) with no difference related either to gender or to scalp
      region. These data were compared with those previously obtained in caucasian
      volunteers of comparable age, and showed significant differences between the two
      ethnic groups in all three parameters studied. Hair density in African volunteers
      was lower than that in caucasians (mean +/- SD 190 +/- 40 and 227 +/- 55 hairs
      cm(-2), respectively). African hair grew at a much slower rate than caucasian
      hair (mean +/- SD 256 +/- 44 vs. 396 +/- 55 microm day(-1)), and telogen counts
      were frequently higher in African hair (mean +/- SD 18 +/- 9% vs. 14 +/- 11%).
      CONCLUSIONS: This study demonstrated significant differences between African and
      caucasian hair growth parameters, which might suggest a trend towards increased
      hair loss in Africans, even though it contrasts with a lower and slower incidence
      of the development of alopecia in Africans.

PMID- 11531796
TI  - Ultrastructure of the hyperhidrotic eccrine sweat gland.
AB  - BACKGROUND: Hyperhidrosis is the secretion of inappropriately large amounts of
      sweat by eccrine glands; it can be very debilitating. Little is known of the
      causes of primary hyperhidrosis. OBJECTIVES: To determine whether the glands
      exhibit any structural abnormality in primary hyperhidrosis. METHODS: Skin
      biopsies were obtained from the axilla (n = 6) or neck (n = 2) of individuals
      aged 26-62 years with primary hyperhidrosis and from five age- and sex-matched
      normal individuals, with informed consent and ethical committee approval. Samples
      were prepared by standard methods for light and electron microscopic examination.
      RESULTS: All characteristics observed in the hyperhidrotic specimens were
      consistent with the changes seen in normal glands following strong activation:
      degranulation of the granular (dark) cells, dilatation of the basolateral
      infoldings and the canaliculi of the non-granular (clear) cells, contraction of
      the myoepithelial cells and thickening of the basal lamina, and presence of
      cellular debris including lipid droplets in the gland lumen. Pathological changes
      were not observed. CONCLUSIONS: The present finding of the absence of structural
      defects in the glands indicates that future studies should concentrate on the
      investigation of neurohumoral or secretory cell metabolic abnormalities.

PMID- 11531798
TI  - Koebner phenomenon due to scratch test in scleromyxoedema.
AB  - The Koebner phenomenon or isomorphic response was originally described in
      psoriasis and has subsequently been observed in various other diseases. We report
      a patient with isomorphic response in scleromyxoedema, a variant of papular
      mucinosis with diffuse infiltration of the skin. The Koebner phenomenon was due
      to a scratch test performed 4 weeks before the appearance of streaky, lichenoid
      infiltrations on the forearms.

PMID- 11531797
TI  - Staphylococcus aureus enterotoxins induce histamine and leukotriene release in
      patients with atopic eczema.
AB  - BACKGROUND: Chronic skin colonization with Staphylococcus aureus is a
      characteristic feature of atopic eczema (AE), and about 60% of S. aureus strains
      isolated from the skin of patients with AE secrete enterotoxins. Furthermore, IgE
      antibodies to S. aureus enterotoxins have been identified in 78% of patients with
      AE. OBJECTIVES: To examine the S. aureus enterotoxin-induced histamine and
      leukotriene release of basophils from patients with AE. METHODS: Peripheral blood
      basophils from patients with AE were stimulated with the staphylococcal
      enterotoxins A, B, D, E and toxic shock syndrome toxin-1. Additionally, priming
      experiments were performed with interleukin (IL)-3, IL-8 and
      granulocyte/macrophage colony-stimulating factor followed by stimulation with S.
      aureus enterotoxins. RESULTS: In patients with AE, basophils secreted
      significantly higher amounts of histamine and leukotriene C4 (LTC4) than in
      healthy controls. The priming experiments showed additional histamine and LTC4
      release in the group of AE patients. CONCLUSIONS: Histamine and leukotriene
      generation from atopic basophils stimulated with staphylococcal enterotoxins may
      indicate a role for these toxins as possible allergens in at least a subgroup of
      patients with AE.

PMID- 11531799
TI  - Cutaneous mastocytosis associated with a mixed germ cell tumour of the ovary:
      report of a case and review of the literature.
AB  - A 10-year-old girl with a mixed germ cell tumour of the ovary, treated by surgery
      and chemotherapy, developed cutaneous mastocytosis approximately 8 months after
      starting chemotherapy. This is the sixth report of a germ cell tumour associated
      with mastocytosis. c-kit receptor point mutations, including Asp816Val and
      Val560Gly were absent in a biopsy specimen obtained from lesional skin.

PMID- 11531800
TI  - Spindle-cell B-cell lymphoma presenting in the skin.
AB  - Lymphomas with predominant spindle-cell morphology have only been previously
      reported in small numbers; such lesions are potentially mistaken for sarcoma or
      other spindle-cell tumours. We describe a 73-year-old woman who presented with a
      tumour on the scalp of a few months' duration. Biopsy showed a B-cell lymphoma of
      follicle centre cell origin with a sarcomatoid appearance and a CD20+, CD10+,
      CD21+, bcl-6+ immunophenotype. This case highlights the very rare occurrence of
      spindle-cell B-cell lymphoma presenting in the skin. An awareness of this
      phenomenon is essential to avoid confusion with a variety of other cutaneous
      spindle-cell neoplasms and to enable a correct diagnosis to be made, thereby
      ensuring that appropriate treatment is initiated.

PMID- 11531801
TI  - Lymphomatoid papulosis with a natural killer-cell phenotype.
AB  - Lymphomatoid papulosis (LyP) is defined as a recurrent self-healing papulonodular
      eruption with the histological features of a (CD30+) cutaneous T-cell lymphoma.
      The atypical cells usually have a CD3+/-, CD4+/-, CD8-, CD30+, CD56- T-cell
      phenotype. We report an unusual case of LyP, in which the atypical cells
      expressed a CD3-, CD4-, CD8-, CD30+, CD56+ phenotype. Detailed phenotypic and
      genotypic analysis confirmed that these cells had a natural killer (NK)-cell
      phenotype. Lymphomas with an NK-cell phenotype usually have a poor prognosis.
      However, the waxing and waning of papular lesions for more than 20 years and the
      excellent response to low-dose oral methotrexate in this patient suggest similar
      clinical behaviour to LyP cases with a T-cell phenotype.

PMID- 11531802
TI  - Rosai-Dorfman disease complicated by autoimmune haemolytic anaemia: case report
      and review of a multisystem disease with cutaneous infiltrates.
AB  - We report a patient with sinus histiocytosis with massive lymphadenopathy (Rosai
      Dorfman disease) who presented with widespread nodal and extranodal involvement
      affecting the skin, orbits and nasal sinuses, complicated by the development of
      autoimmune haemolytic anaemia. The aetiology and pathogenesis of this multisystem
      disorder are unknown but are thought to represent a reactive histiocytic process
      to an infective agent rather than a neoplastic or other primary condition.
      Prognosis is generally good but clinical or laboratory evidence of immune
      dysfunction tends to predict a poorer outcome. We describe the clinical course of
      the patient and review the literature on this disease.

PMID- 11531803
TI  - Metastatic melanoma to the palatine tonsil with a favourable prognosis.
AB  - Metastasis to the oral cavity from cutaneous melanoma is rare: fewer than 30
      cases of metastatic melanoma to the palatine tonsil have been reported. Tonsil
      metastasis is haematogenously disseminated and therefore usually has a poor
      prognosis. We present a case of metastatic melanoma to the palatine tonsil
      occurring 6(1/2) years after removal of the primary cutaneous lesion. The patient
      has remained disease-free for 18 months since the removal of skin and tonsil
      metastases. Immunohistopathologically, HLA class II and costimulatory factor B7-2
      molecules were concomitantly expressed on melanoma cells: we suggest that the
      patient was therefore able to develop antimelanoma T-cell activation resulting in
      prevention of further metastasis, and thus a favourable prognosis.

PMID- 11531804
TI  - New mutations in keratin 1 that cause bullous congenital ichthyosiform
      erythroderma and keratin 2e that cause ichthyosis bullosa of Siemens.
AB  - The intermediate filaments of epithelial cells are formed by keratins, a family
      of structurally related proteins, which are expressed in pairs of acidic (type I)
      and basic (type II) polypeptides in a tissue- and differentiation-specific
      manner. Mutations in the genes encoding several keratins have been implicated in
      the pathogenesis of diseases of keratinization. We report molecular analysis of
      two patients with the rare autosomal dominant disorders bullous congenital
      ichthyosiform erythroderma (BCIE) and ichthyosis bullosa of Siemens (IBS).
      Previous studies have shown that these genodermatoses are due to mutations in the
      KRT1 and KRT2E genes, respectively. We report a new amino acid substitution
      mutation in codon 155 of KRT1 (valine to aspartic acid) in the conserved H1
      domain of the protein in the patient with BCIE. We also report a novel amino acid
      substitution mutation in codon 192 of KRT2E (asparagine to lysine) in the
      conserved 1A helix initiation peptide of the protein in the patient with IBS. Our
      results demonstrate that these mutations are deleterious to keratin filament
      network stability and lead to specific clinical inherited disorders of
      keratinization.

PMID- 11531805
TI  - Aspirin enhances the induction of type I allergic symptoms when combined with
      food and exercise in patients with food-dependent exercise-induced anaphylaxis.
AB  - We examined the effect of aspirin as a substitute for exercise in inducing
      urticaria/anaphylaxis in three patients with food-dependent exercise-induced
      anaphylaxis (FDEIA). Two of the patients had specific IgE antibodies to wheat and
      the other had antibodies to shrimp. Administration of aspirin before ingestion of
      food allergens induced urticaria in one patient and urticaria and hypotension in
      another, while aspirin alone or food alone elicited no response. The third
      patient developed urticaria only when he took all three items, i.e. aspirin, food
      and additional exercise, whereas provocation with any one or or two of these did
      not induce any symptoms. These findings suggest that aspirin upregulates type I
      allergic responses to food in patients with FDEIA, and further shows that aspirin
      synergizes with exercise to provoke symptoms of FDEIA. This is the first report
      of a synergistic effect of aspirin in inducing urticaria/anaphylaxis, which was
      confirmed using challenge tests in patients with FDEIA.

PMID- 11531806
TI  - Methotrexate-responsive chronic idiopathic urticaria: a report of two cases.
AB  - Chronic idiopathic urticaria (CIU) may be severe and refractory to standard
      therapies. We describe two patients with CIU, neither of whom had detectable
      autoantibodies, in whom control of the disease was achieved with methotrexate.

PMID- 11531807
TI  - Trichophyton rubrum showing deep dermal invasion directly from the epidermis in
      immunosuppressed patients.
AB  - Trichophyton rubrum is the most widely encountered dermatophyte infection, and is
      usually regarded as exclusively keratinophilic often leading to chronic cutaneous
      and nail infections, even in healthy individuals. We present three patients with
      acute leukaemias, with ill-defined pre-existent cutaneous eruptions that were
      treated with a potent topical corticosteroid. All three patients received
      aggressive marrow toxic chemotherapy. These patients had progression of their
      cutaneous disease, which showed deep dermal invasion of T. rubrum, invading
      directly from the epidermis with no evidence of systemic spread. We conclude that
      systemic pancytopenia, in association with prolonged local immunosuppression, may
      increase the risk of direct dermal invasion of dermatophyte infections. However,
      even in these patients, the risk of systemic spread still appears very low.
      Amphotericin B did not appear effective in treating these dermatophyte
      infections.

PMID- 11531808
TI  - Spitz naevus showing clinical features of both granuloma pyogenicum and pigmented
      naevus.

PMID- 11531809
TI  - Efficacy of basiliximab, a chimeric anti-interleukin-2 receptor monoclonal
      antibody, in a patient with severe chronic atopic dermatitis.

PMID- 11531810
TI  - Treatment of atopic dermatitis with mycophenolate mofetil.

PMID- 11531811
TI  - A comparison of the effect of narrow-band ultraviolet B in the treatment of
      psoriasis after salt-water baths and after 8-methoxypsoralen baths.

PMID- 11531812
TI  - Successful ultraviolet A1 treatment of cutaneous sarcoidosis.

PMID- 11531813
TI  - Eczema craquele resulting from acute oedema: a report of seven cases.

PMID- 11531814
TI  - Linear erythema craquele due to acute oedema in anorexia nervosa.

PMID- 11531815
TI  - Lichenoid vasculitis associated with myeloproliferative disorder: successful
      treatment with dapsone.

PMID- 11531816
TI  - Granuloma faciale with extrafacial lesions.

PMID- 11531817
TI  - Schonlein-Henoch purpura associated with losartan treatment and presence of
      antineutrophil cytoplasmic antibodies of x specificity.

PMID- 11531818
TI  - Chronic glomerulonephritis remarkably improved after surgery for acne conglobata
      of the buttocks.

PMID- 11531819
TI  - Dystrophic calcinosis cutis in venous ulcers: a cause of treatment failure.

PMID- 11531820
TI  - Angiolymphoid hyperplasia with eosinophilia in the oral mucosa.

PMID- 11531821
TI  - Intraosseous epidermoid cyst mimicking psoriasis.

PMID- 11531822
TI  - Dose thresholds and local anhidrotic effect of botulinum A toxin injections
      (Dysport).

PMID- 11531823
TI  - Xanthogranuloma is the archetype of non-Langerhans cell histiocytoses.

PMID- 11531826
TI  - CONSORT your submissions: an update for authors.

PMID- 11531827
TI  - What's new in atopic dermatitis?

PMID- 11531828
TI  - The therapeutic use of topical contact sensitizers in benign dermatoses.
AB  - Topical therapy using contact sensitizers has been practised since the 1960s to
      treat conditions associated with an altered immunological state.
      Dinitrochlorobenzene, squaric acid dibutyl ester and diphencyprone are most
      commonly employed in the therapy of alopecia areata and viral warts. Few
      dermatology departments in the U.K. provide such treatment. This systematic
      review discusses the various contact sensitizers used for topical immunotherapy,
      the methodology of treatment, factors influencing efficacy and likely adverse
      effects.

PMID- 11531829
TI  - Mucous membrane pemphigoid: HLA-DQB1*0301 is associated with all clinical sites
      of involvement and may be linked to antibasement membrane IgG production.
AB  - BACKGROUND: Class I human leucocyte antigens (HLA) -A, -B, -Cw and class II HLA
      DRB1, -DQB1 alleles were determined in 131 British Caucasian patients with mucous
      membrane pemphigoid (MMP) using serological and DNA-based methods. OBJECTIVES: To
      analyse the class I and II alleles expressed in well-defined clinical and
      immunopathological subgroups of MMP, in order to establish whether specific
      alleles or haplotypes might in part explain disease susceptibility, clinical
      sites of involvement or disease severity. METHODS: Subgroups of patients were
      analysed according to the following clinical criteria: age of onset, sex, sites
      of clinical involvement (oral, ocular, skin, nasal, genital, pharyngeal,
      oesophageal, laryngeal, perianal), disease severity and history of autoimmune
      disease. Subgroups were also analysed according to the following
      immunopathological criteria: autoantibody profile, the presence of circulating
      antibasement membrane IgG or IgA antibodies and the detection of target basement
      membrane zone (BMZ) antigens (BP230 and BP180) by IgG autoantibodies. RESULTS:
      Class I HLA typing showed no significant disease or subgroup associations. Class
      II DRB1 typing showed a significantly increased allelic frequency in MMP vs.
      controls for DRB1*11 (RR = 2.08, Pc < 0.0000056). For DQB1, MMP vs. controls,
      there was a significantly increased allelic frequency for DQB1*0301 (Pc <
      0.00000028) in both males and females; all clinical sites of involvement, with
      the exception of laryngeal, oesophageal and perianal sites and in patients with
      detectable circulating anti-BMZ IgG compared with those negative for IgG (P <
      0.0096, Pc < 0.019). A positive trend was noted in patients with ocular
      involvement compared with no ocular involvement and in patients with a clinical
      score > or = 10 compared with < 10. We found no difference in DQB1*0301 allele
      frequency between subgroups with or without BP180 or BP230 target antigens.
      Haplotype frequencies showed an increase in DRB1*04, DQB1*0301 (Pc < 0.000066)
      and DRB1*11, DQB1*0301 (Pc < 0.000002) among patients compared with controls.
      CONCLUSIONS: The DQB1*0301 allele confers a predisposition to all subgroups of
      MMP and may have a role in T-cell recognition of basement membrane antigens,
      resulting in the production of anti-BMZ IgG autoantibodies. The positive trend
      between increased allelic expression of DQB1*0301 in patients with ocular disease
      and in those with a higher clinical score, further suggests a role for this
      allele in disease severity.

PMID- 11531830
TI  - Impaired responses of peripheral blood mononuclear cells to T-cell stimulants in
      alopecia areata patients with a poor response to topical immunotherapy.
AB  - BACKGROUND: Topical immunotherapy with a contact allergen is effective in
      alopecia areata (AA). However, the mechanism of the effect is still unknown, and
      pretreatment prediction of the outcome of therapy in each patient remains
      difficult. OBJECTIVES: To predict the clinical effect of this therapy in AA
      patients, we investigated the relationship between clinical responses to topical
      immunotherapy and in vitro proliferative responses of peripheral blood
      mononuclear cells (PBMC) to T-cell stimulants. METHODS: PBMC were taken from 67
      AA patients before or during diphenylcyclopropenone immunotherapy and from 14
      healthy controls, and proliferative responses to phytohaemagglutinin and
      staphylococcal enterotoxin B were evaluated by measuring [3H]-thymidine
      incorporation. RESULTS: PBMC from the AA patients with a good clinical response
      to immunotherapy showed a normal level of proliferation, whereas PBMC from the
      poor responders showed a markedly suppressed proliferative response and
      interleukin (IL)-2 production, but increased IL-4 production compared with the
      controls. CONCLUSIONS: The proliferative response of PBMC to T-cell stimulants
      may be one of the indicators of the clinical effect of topical immunotherapy for
      AA.

PMID- 11531831
TI  - A study of apolipoproteins E and A-I in cutaneous amyloids.
AB  - BACKGROUND: Apolipoprotein E (apoE) is present in a variety of biochemically
      different amyloid deposits, including Alzheimer's disease, systemic amyloidosis
      and primary cutaneous amyloidosis (PCA). Among the three closely related alleleic
      forms of apoE, the epsilon4 allele is linked to Alzheimer's disease.
      Apolipoprotein A-I (apoA-I), another apolipoprotein, is also found in senile
      plaques of Alzheimer's disease and in amyloid of aortic atherosclerotic plaques.
      Furthermore, apoA-I has recently been found to be associated with hereditary
      cutaneous and cardiac amyloidosis. OBJECTIVES: To determine whether the apoE
      epsilon4 allele is associated with increased risk of PCA and whether apoE and
      apoA-I are present in PCA and common secondary cutaneous amyloidosis (SCA) (i.e.
      basal cell carcinoma, Bowen's disease and seborrhoeic keratosis). METHODS: We
      examined the apoE genotype in 57 Chinese patients with PCA and 58 normal healthy
      control subjects of similar age. In addition, immunohistochemical staining was
      performed to determine the localization of apoE and apoA-I in skin tissues from
      15 patients with SCA and 15 with PCA. RESULTS: The frequency of the epsilon4
      allele in the PCA group was not significantly higher than that in the control
      group (8.8% vs. 6.9%, P > 0.05). ApoE was present in amyloid deposits in both PCA
      and SCA, but apoA-I was not detected in these cutaneous amyloid deposits.
      CONCLUSIONS: ApoE is also a component of amyloid deposits in SCA. Although the
      genetic susceptibility of certain apoE isoforms may not be a crucial factor in
      the development of PCA and, although apoA-I is not associated with amyloid
      deposits of PCA and SCA, the role of apolipoproteins in amyloidogenesis deserves
      further scrutiny.

PMID- 11531832
TI  - Evaluation of diagnostic criteria for atopic dermatitis: validity of the criteria
      of Williams et al. in a hospital-based setting.
AB  - BACKGROUND: Surveys of the prevalence of atopic dermatitis (AD) have been carried
      out world-wide, but the results vary widely. The differences probably result from
      the use of different diagnostic criteria. Williams et al. proposed minimum,
      simplified, diagnostic criteria that require no invasive test and are easy to
      use. Pilot studies in European countries showed their suitability for
      implementation both in hospitals and in the community, and their high sensitivity
      and specificity. OBJECTIVES: To evaluate the potential practical value of the
      criteria of Williams et al. in the Chinese population. METHODS: The criteria of
      Hanifin and Rajka (gold standard), Williams et al. and Kang and Tian were applied
      and compared in 111 patients with AD and 121 control subjects with other skin
      diseases in three out-patient centres in China. RESULTS: The criteria of Williams
      et al. showed a similar diagnostic efficiency to that of the gold standard, with
      the sensitivity, specificity and kappa value reaching 95.50%, 97.52% and 0.93,
      respectively. No significant difference was found between the criteria of
      Williams et al. and those of Kang and Tian (chi2 = 0.69, P > 0.05). 'Onset under
      the age of 2 years', a criterion of Williams et al. could be used in subjects of
      any age. CONCLUSIONS: The diagnostic efficiency of the criteria of Williams et
      al. was basically similar to those of Hanifin and Rajka and of Kang and Tian in
      our out-patient settings. However, those of Williams et al. were easier to apply
      and required no invasive tests.

PMID- 11531833
TI  - Cutaneous larva migrans: clinical features and management of 44 cases presenting
      in the returning traveller.
AB  - BACKGROUND: Cutaneous larva migrans (CLM) is the result of a nematode infection,
      and shows a characteristic creeping eruption. As travel to the tropics increases,
      many British citizens may be returning with this infection, which is often
      misdiagnosed or treated incorrectly. OBJECTIVES: To perform a retrospective
      survey of 44 cases of CLM presenting to the Hospital for Tropical Diseases in
      London over the last 2 years. METHODS: Cases were reviewed with regard to patient
      characteristics, source of infection, source of referral, clinical features and
      therapy. RESULTS: Most infections were acquired in Africa (32%), the Caribbean
      (30%) and South-east Asia (25%), but also in Central and South America. There was
      a history of exposure to a beach in 95% of patients and the median duration of
      symptoms was 8 weeks (range 1-104). Lesions mainly affected the feet (39%),
      buttocks (18%) and abdomen (16%), but the lower leg, arm and face were also
      affected. Multiple lesions were seen in seven of 44 cases (16%). Laboratory
      abnormalities were absent in all patients. Of 44 patients seen, four needed no
      treatment, 28 were cured by a single course of treatment, 11 required a second
      course of therapy and one patient was treated three times. Thirty-one patients
      received oral albendazole 400 mg daily for 3-5 days and 24 were cured (77%). Five
      patients received 10% thiabendazole cream topically for 10 days and four were
      cured (80%). Four patients received oral thiabendazole 1.5 g daily for 3 days and
      all required further therapy. CONCLUSIONS: In view of the range of treatment
      regimens recorded, a randomized controlled trial comparing topical and systemic
      therapies is warranted.

PMID- 11531834
TI  - Efficacy of sirolimus (rapamycin) administered concomitantly with a
      subtherapeutic dose of cyclosporin in the treatment of severe psoriasis: a
      randomized controlled trial.
AB  - BACKGROUND: The identification of a highly potent
      immunosuppressive/antiproliferative agent with an acceptable toxicity profile has
      long been a goal for the management of severe plaque psoriasis. OBJECTIVES: To
      investigate the efficacy and safety of sirolimus (Rapamune) for severe psoriasis
      when given alone or in association with cyclosporin. METHODS: In a randomized,
      double-blind, eight parallel group, pilot study in 24 out-patient centres in
      seven European countries, 150 patients, 18 years and older, with severe chronic
      plaque psoriasis were given sirolimus 0.5, 1.5 and 3.0 mg m(-2) daily for 8
      weeks, either alone or in association with a subtherapeutic dose of cyclosporin
      (1.25 mg kg(-1) daily). Cyclosporin 5 mg kg(-1) daily was the positive control
      and cyclosporin 1.25 mg kg(-1) daily the negative control. The primary efficacy
      variable was the mean percentage reduction in Psoriasis Area and Severity Index
      (PASI). Safety assessments included monitoring of adverse events, clinical
      laboratory parameters and sirolimus/cyclosporin blood concentrations. RESULTS:
      The greatest mean percentage decreases in PASI were seen with cyclosporin 5.0 mg
      kg(-1) daily (70.5%) and with sirolimus 3.0 mg m(-2) daily + cyclosporin 1.25 mg
      kg(-1) daily (63.7%). Both groups demonstrated significantly better results than
      cyclosporin 1.25 mg kg(-1) daily (mean decrease 33.4%). Serum creatinine levels
      were significantly lower for groups with sirolimus alone and sirolimus plus
      reduced-dose cyclosporin when compared with cyclosporin 5.0 mg kg(-1) daily.
      Adverse events associated with sirolimus included thrombocytopenia (5%),
      hyperlipidaemia (9%), aphthous stomatitis (9%) and acne (13%), whereas adverse
      events associated with cyclosporin included hot flushes (12%), hyperlipidaemia
      (9%) and increased serum creatinine (9%). CONCLUSIONS: The concomitant
      administration of sirolimus with a subtherapeutic dose of cyclosporin in severe
      psoriasis may permit a reduction in their respective toxicities, notably
      cyclosporin-induced nephrotoxicity.

PMID- 11531835
TI  - Long-term efficacy of antifungals in toenail onychomycosis: a critical review.
AB  - BACKGROUND: Modern antifungal drugs achieve high mycological and clinical cure
      rates in onychomycosis of the toes, but little is known about the long-term
      evolution of the treated patients. OBJECTIVES: The aim of this review was to
      analyse the therapeutic results recorded more than 1 year after initiation of
      therapy. METHODS: We used two endpoints for the analysis: EP1 (the number of
      patients with negative mycology after follow-up, divided by the number of
      patients included at day 0, including all patients lost to follow-up), and EP2
      (the number of patients with negative mycology after follow-up divided by the
      number of patients with negative mycology at week 48). Clinical cure rate
      (EPclin) was the number of patients clinically cured or with minimal residual
      lesions divided by the number of patients included at day 0. RESULTS: From a
      Medline search we identified 17 studies providing results beyond 48 weeks.
      Ketoconazole 200 mg d(-1) up to 1 year resulted in EP1 of 11% at 18 months, and
      EP2 of 43%. Griseofulvin 1 g d(-1) for 1 year allowed an EP1 of 43% at 18 months,
      and EP2 of 71%. The mean EP1 after fluconazole once weekly up to 1 year was 49%
      at 18 months, and EP2 was 91%. With itraconazole 200 mg d(-1) or 400 mg d(-1) for
      1 week each month for 3-4 months, EP1 was 37% at 18 months, and 53% at 2 years;
      EP2 was 76% at 4 years. Terbinafine 250 mg d(-1) for 12-16 weeks achieved an EP1
      of 62% at 18 months, 72% at 2 years, and 60% at 4 years; EP2 was 80% at 18
      months, 81% at 2 years, and 71% at 4 years. In the only study planned to compare
      the long-term efficacy of terbinafine and itraconazole, EP1 at 18 months was
      significantly higher with continuous terbinafine than with intermittent
      itraconazole (66% vs. 37%, P < 0.001). The clinical cure rates were 21% at 60
      weeks and 37% at 72 weeks with fluconazole. EPclin was 27% at 18 months and 35%
      at 2 years with itraconazole. EPclin was 48% at 18 months, 69% at 2 years and 50%
      at 4 years with terbinafine. CONCLUSIONS: Considering the stringency of the
      criteria we used, this critical review suggests that the long-term efficacy
      achieved with terbinafine is superior to that obtained with griseofulvin,
      ketoconazole, fluconazole or itraconazole.

PMID- 11531836
TI  - Occupational skin diseases in Northern Bavaria between 1990 and 1999: a
      population-based study.
AB  - BACKGROUND: Occupational skin diseases (OSDs) account for a large portion of
      occupational diseases in Europe, but population-based epidemiological studies are
      missing. OBJECTIVES: We analysed the initial reports of OSDs in our register of
      OSDs in Northern Bavaria (BKH-N). METHODS: A total of 5285 cases were assessed
      prospectively and registered from 1990 to 1999. As the German Federal Employment
      Office provides specific occupational data in relation to the total employed
      population of Northern Bavaria, it was possible to conduct a population-based
      study that investigated the trend in incidence rates between two study periods
      (1990-92 and 1993-99) in 24 different occupational groups. RESULTS: A total of
      3097 cases of OSD (median age 25 years) were recorded in the 24 occupational
      groups. There was a significant decline (P < 0.001) in the overall incidence rate
      of OSD with 10.7 cases per 10,000 workers per year for the first study period and
      4.9 cases per 10,000 workers per year for the second study period. This general
      trend in incidence rates was also significant for hairdressers and barbers,
      bakers, health-care workers, cooks and metal processors. CONCLUSIONS: The BKH-N
      provides national data based on the notification of OSDs in Germany. The results
      demonstrate the rank of occupations hazardous for the skin and are helpful for
      defining target groups for prevention.

PMID- 11531837
TI  - A clinical and therapeutic study of 29 patients with infantile acne.
AB  - BACKGROUND: Infantile acne is a relatively uncommon condition; there are few data
      in the literature on the optimum treatment for this disorder. OBJECTIVES: To
      review treatment results in infantile acne. METHODS: We performed a retrospective
      review of 29 patients (24 boys and five girls) treated over a 25-year period.
      RESULTS: The age at onset was 6-16 months (median 9). The acne was mild in 24%,
      moderate in 62% and severe in 14%. The type of acne was predominantly
      inflammatory (59%), but was comedonal in 17%, showed a mixed pattern in 17% and
      was nodular in 7%. No infants had any clinically obvious endocrinopathy. Patients
      with mild acne responded well to topical treatment (benzoyl peroxide,
      erythromycin and retinoids). All but two infants with moderate acne responded
      well to oral (paediatric) erythromycin 125 mg twice daily and topical therapy.
      Patients with erythromycin-resistant Propionibacterium acnes required
      trimethoprim 100 mg twice daily. Most patients were able to stop oral antibiotics
      within 18 months. In 38% of children, long-term oral antibiotics (> 24 months)
      were required. The time for clearance of the acne was 6-40 months (median 18).
      One patient required oral isotretinoin that cleared the acne in 4 months. Five
      patients (17%) were left with scarring. CONCLUSIONS: This study confirms the male
      predominance of infantile acne. Treatment is similar to that of adult acne, with
      the exclusion of the use of tetracyclines. When necessary, oral isotretinoin can
      be used.

PMID- 11531838
TI  - A follow-up study of recurrence and cosmesis in completely responding superficial
      and nodular basal cell carcinomas treated with methyl 5-aminolaevulinate-based
      photodynamic therapy alone and with prior curettage.
AB  - BACKGROUND: Methyl 5-aminolaevulinate (mALA) is an ester derivative of 5
      aminolaevulinic acid (ALA) with increased lipophilicity compared with ALA.
      OBJECTIVES: To assess long-term cure rate, cosmesis, recurrence rate and extent
      of fibrosis after mALA-based photodynamic therapy (PDT) of superficial and
      nodular basal cell carcinomas (BCCs) showing early complete response to
      treatment. METHODS: Of 350 BCCs treated, 310 responded completely. These were in
      59 patients who were followed for 2-4 years (mean 35 months) after mALA-PDT.
      Nodular tumours were curetted before PDT, and mALA 160 mg g(-1) was applied to
      all tumours for 24 h or 3 h before illumination from a broad-band halogen light
      source with light doses from 50 to 200 J cm(-2). Fibrosis was assessed
      histologically in 23 biopsies. RESULTS: The overall cure rate for 350 BCCs,
      including non-responders and recurrences was 79%. Of 310 lesions, 277 (89%)
      remained in complete response, and the cosmetic outcome was excellent or good in
      272 of the completely responding lesions (98%). Histological examination showed
      dermal fibrosis in one of 23 biopsies. CONCLUSIONS: We conclude that mALA-based
      PDT with prior curettage of nodular lesions is a promising new method for the
      treatment of BCC.

PMID- 11531839
TI  - Is the efficacy of psoralen plus ultraviolet A therapy for vitiligo enhanced by
      concurrent topical calcipotriol? A placebo-controlled double-blind study.
AB  - BACKGROUND: Encouraging results of previous uncontrolled trials suggest that
      calcipotriol may potentiate the efficacy of psoralen plus ultraviolet (UV) A
      (PUVA) therapy in patients with vitiligo. OBJECTIVES: We performed a placebo
      controlled double-blind study to investigate whether the effectiveness of PUVA
      treatment could be enhanced by combination with topical calcipotriol in the
      treatment of vitiligo. METHODS: Thirty-five patients with generalized vitiligo
      enrolled in the study. Symmetrical lesions of similar dimensions and with no
      spontaneous repigmentation on arms, legs or trunk were selected as reference
      lesions. In this randomized left-right comparison study, calcipotriol 0.05 mg g(
      1) cream or placebo was applied to the reference lesions 1 h before PUVA
      treatment (oral 8-methoxypsoralen and conventional UVA units) twice weekly.
      Patients were examined at weekly intervals. The mean number of sessions and the
      cumulative UVA dosage for initial and complete repigmentation were calculated.
      RESULTS: Twenty-seven patients (nine women, 18 men; mean +/- SEM age 29.8 +/-
      13.5 years) were evaluated. The mean +/- SEM cumulative UVA dose and number of
      UVA exposures for initial repigmentation were 52.52 +/- 6.10 J cm(-2) and 9.33 +/
      0.65 on the calcipotriol side, and 78.20 +/- 7.88 J cm(-2) and 12.00 +/- 0.81 on
      the placebo side, respectively (P < 0.001). For complete repigmentation,
      respective values were 232.79 +/- 14.97 J cm(-2) and 27.40 +/- 1.47 on the
      calcipotriol side and 259.93 +/- 13.71 J cm(-2) and 30.07 +/- 1.34 on the placebo
      side (P = 0.001). Treatment with calcipotriol and PUVA resulted in significantly
      higher percentages of repigmentation for both initial (81%) and complete
      pigmentation (63%), compared with placebo and PUVA (7% and 15%, respectively).
      CONCLUSIONS: Our results have shown that concurrent topical calcipotriol
      potentiates the efficacy of PUVA in the treatment of vitiligo, and that this
      combination achieves earlier pigmentation with a lower total UVA dosage.

PMID- 11531840
TI  - Topical calcipotriol as monotherapy and in combination with psoralen plus
      ultraviolet A in the treatment of vitiligo.
AB  - BACKGROUND: Recent advances in the pathophysiology of vitiligo have demonstrated
      defective calcium homeostasis in depigmented skin. 1,25-Dihydroxyvitamin D3 may
      be involved in the regulation of melanin synthesis, and receptors for 1,25
      dihydroxyvitamin D3 have been demonstrated on melanocytes. OBJECTIVES: We
      conducted an open study to determine the efficacy and tolerability of
      calcipotriol cream as monotherapy and in conjunction with psoralen plus
      ultraviolet A (PUVA) in the treatment of vitiligo. METHODS: Twenty-six patients
      with vitiligo affecting 5-40% of their skin were recruited. Twenty-two were
      treated with twice-daily topical calcipotriol monotherapy (50 microg g(-1)) and
      four were placed on combination treatment with twice-daily topical calcipotriol
      50 microg g(-1) in conjunction with topical or oral 8-methoxypsoralen PUVA three
      times weekly. RESULTS: Treatment was well tolerated at all sites and no adverse
      effects were reported. After a therapy time of 3-9 months (mean 6 months), 77%
      (17 of 22) of those treated with monotherapy showed 30-100% improvement, and
      three of the four patients on combination treatment showed good response.
      CONCLUSIONS: Topical calcipotriol appears to be an effective and well-tolerated
      treatment for vitiligo and can be safely used in conjunction with PUVA, but
      controlled studies are necessary to exclude the possibility of spontaneous
      repigmentation.

PMID- 11531841
TI  - Ultrastructural features resembling those of harlequin ichthyosis in patients
      with severe congenital ichthyosiform erythroderma.
AB  - Congenital ichthyoses are a group of heterogeneous disorders of cornification.
      Autosomal recessive congenital ichthyosis (ARCI) can be clinically subdivided
      into congenital ichthyosiform erythroderma and lamellar ichthyosis.
      Ultrastructurally, ARCI is classified into four groups: ichthyosis congenita (IC)
      types I-IV. The genetic background of the ARCI disorders is heterogeneous, but
      only one disease gene, transglutaminase 1, has been detected so far. We describe
      six patients with severe congenital ichthyosis from six different Scandinavian
      families. They could not be classified ultrastructurally into the four IC groups
      because of atypical findings of electron microscopy. These included abnormal
      lamellar bodies, alterations in keratohyalin, remnant organelles and lipid
      inclusions in the upper epidermal cells, which resembled the ultrastructural
      findings of harlequin ichthyosis (HI), although the HI phenotype was not present
      at birth. Some clinical features, such as thick scales, erythroderma, alopecia
      and ectropion were common to all patients. Ichthyosis was usually accentuated in
      the scalp and four patients had clumped fingers and toes. None of the patients
      carried the transglutaminase 1 mutation. We conclude that ultrastructural
      findings resembling those detected in previous HI cases (type 1 and 2) can also
      be found in patients who do not have classic clinical features of that rare
      ichthyosis. This may be due to lack of specificity of ultrastructural markers for
      HI or to its clinical heterogeneity.

PMID- 11531842
TI  - Sporotrichoid phaeohyphomycosis due to Alternaria infectoria.
AB  - We describe a cardiac transplant patient who had human cutaneous alternariosis
      with a sporotrichoid distribution of skin lesions. In this patient identification
      of the causative organism Alternaria infectoria was achieved by sequencing the
      rDNA internal transcribed spacer domain. Treatment with itraconazole led to
      clinical resolution within 4 months.

PMID- 11531843
TI  - A case of gnathostomiasis in a European traveller returning from Mexico.
AB  - Hundreds of human cases of gnathostomiasis have recently been reported from
      Mexico, where the disease is becoming a public health problem. We report a case
      of gnathostomiasis in a French tourist returning from Mexico. Tourists travelling
      in endemic countries are at risk of gnathostomiasis and should be advised about
      the risks of eating raw fish as a suspected source of infection.

PMID- 11531844
TI  - Flexural erythematous eruption following autologous peripheral blood stem cell
      transplantation: a study of four cases.
AB  - Autologous bone marrow transplantation and autologous peripheral blood stem cell
      transplantation (APBSCT) are alternative therapeutic options in the treatment of
      various malignancies. We describe four patients undergoing APBSCT for
      malignancies; they developed a cutaneous eruption characterized by confluent
      erythematous and hyperpigmented patches within the flexural areas during the
      first month after transplantation. The lesions were poorly circumscribed without
      epidermal changes such as scaling, xerosis, erosions or atrophy. The skin patches
      were treated with topical corticosteroids and resolved within a few days with
      discoloration. Histopathological findings were characterized by focal vacuolar
      degeneration of the basal layer with epidermal dysmaturation. We believe that
      these cutaneous eruptions are consistent with an interplay of high-dose
      chemotherapy and local factors such as friction, local skin temperature and
      eccrine gland distribution, which could explain the constant location of this
      eruption in the axillae and genital area.

PMID- 11531845
TI  - Epithelioid blue naevus of the genital mucosa: report of four cases.
AB  - Epithelioid blue naevi are an unusual cytological variant of blue naevus that
      have been recently described mostly in patients with the Carney complex, although
      they may also occur in isolation. This variant of blue naevus is composed of
      melanin-laden polygonal epithelioid melanocytes situated within the dermis. The
      neoplastic cells show no maturation with progressive depth of dermal infiltration
      and, in contrast with the usual stromal changes in blue naevi, epithelioid blue
      naevi exhibit no dermal fibrosis. We describe four cases of epithelioid blue
      naevus located on the genital mucosa in four patients with no evidence of the
      Carney complex. Three male patients showed an epithelioid blue naevus on the
      mucosa of the glans penis and a female patient had a lesion of the right labium
      minoris. Histopathologically, the lesions consisted of entirely intradermal
      melanocytic naevi composed mostly of heavily pigmented epithelioid melanocytes
      involving the dermis of the genital mucosa. Immunohistochemically, in all cases,
      epithelioid melanocytes expressed immunoreactivity for S-100 protein, HMB-45,
      Melan-A and MiTF antibodies.

PMID- 11531846
TI  - Topical 5-aminolaevulinic acid photodynamic therapy for extensive scalp actinic
      keratoses.
AB  - Scalp actinic keratoses (AKs) are common, particularly in elderly bald males.
      Cryotherapy and 5-fluorouracil are effective for localized AKs but are limited in
      extensive disease. Topical 5-aminolaevulinic acid photodynamic therapy (5-ALA
      PDT) is an alternative. We treated four patients with extensive scalp AKs with
      low light dose, low dose-rate topical 5-ALA PDT using a broad-spectrum visible
      light source. Three patients cleared and one showed significant improvement.
      Remission lasted 6 months.

PMID- 11531847
TI  - Carcinoma arising in epidermoid cyst: a case series and aetiological
      investigation of human papillomavirus.

PMID- 11531848
TI  - Oral acanthosis nigricans, the sign of Leser-Trelat and cholangiocarcinoma.

PMID- 11531849
TI  - Naevoid basal cell carcinoma syndrome with a palmar epidermoid cyst, milia and
      maxillary cysts.

PMID- 11531850
TI  - Hydroa vacciniforme with latent Epstein-Barr virus infection.

PMID- 11531851
TI  - Primary brain B-cell lymphoma developing in a patient with pemphigus vulgaris
      receiving immunosuppressive drugs.

PMID- 11531852
TI  - Acral pseudolymphomatous angiokeratoma of children: a pseudolymphoma rather than
      an angiokeratoma.

PMID- 11531853
TI  - Eosinophilic pustular folliculitis treated with naproxen.

PMID- 11531854
TI  - Second case of papular-purpuric gloves-and-socks syndrome related to hepatitis B
      infection.

PMID- 11531855
TI  - Chronic urticaria associated with dental infection.

PMID- 11531856
TI  - Chronic dermatophytosis in lamellar ichthyosis: relevance of a T-helper 2-type
      immune response to Trichophyton rubrum.

PMID- 11531857
TI  - Onychomadesis and onycholysis associated with capecitabine.

PMID- 11531858
TI  - Lichen planopilaris coexisting with erythema dyschromicum perstans.

PMID- 11531859
TI  - Postoperative futility: a clinical algorithm for setting limits.

PMID- 11531860
TI  - Confidentiality and healthcare.

PMID- 11531861
TI  - Systematic review of the definition and measurement of anastomotic leak after
      gastrointestinal surgery.
AB  - BACKGROUND: Anastomotic leak after gastrointestinal surgery is an important
      postoperative event that leads to significant morbidity and mortality.
      Postoperative leak rates are frequently used as an indicator of the quality of
      surgical care provided. Comparison of rates between and within institutions
      depends on the use of standard definitions and methods of measurement of
      anastomotic leak. The aim of this study was to review the definition and
      measurement of anastomotic leak after oesophagogastric, hepatopancreaticobiliary
      and lower gastrointestinal surgery. METHODS: A systematic review was undertaken
      of the published literature. Searches were carried out on five bibliographical
      databases (Medline, Embase, The Cochrane Library, Cumulative Index for Nursing
      and Allied Health Literature and HealthSTAR) for English language articles
      published between 1993 and 1999. Articles were critically appraised by two
      independent reviewers and data on definition and measurement of anastomotic leak
      were extracted. RESULTS: Ninety-seven studies were reviewed and a total of 56
      separate definitions of anastomotic leak were identified at three sites: upper
      gastrointestinal (13 definitions), hepatopancreaticobiliary (14) and lower
      gastrointestinal (29). The majority of studies used a combination of clinical
      features and radiological investigations to define and detect anastomotic leak.
      CONCLUSION: There is no universally accepted definition of anastomotic leak at
      any site. The definitions and values used to measure anastomotic failure vary
      extensively and preclude accurate comparison of rates between studies and
      institutions.

PMID- 11531862
TI  - Penetrating atherosclerotic ulcers of the aorta.
AB  - BACKGROUND: Penetrating aortic ulcers burrow into the aortic wall and can have
      fatal consequences. Although they were first described as long ago as 1934 they
      have only recently been recognized as a distinct pathological entity. METHOD: A
      review of the current literature was undertaken, based primarily on an English
      language Medline search with secondary references obtained from key articles.
      RESULTS: Penetrating aortic ulcer is principally a disease of elderly
      hypertensive men. It may run a benign course or may produce complications such as
      aortic rupture, embolization and aneurysm formation. Presentation may be
      identical to that of classical aortic dissection, but the distinction is
      important because an ulcer may be more likely to cause rupture. CONCLUSION: Open
      surgical repair has been the 'gold standard' of treatment but endovascular
      stenting is an attractive option in this group of frail patients.

PMID- 11531863
TI  - Prospective randomized double-blind placebo-controlled trial of glyceryl
      trinitrate in endoscopic retrograde cholangiopancreatography-induced
      pancreatitis.
AB  - BACKGROUND: One possible aetiology of pancreatitis following endoscopic
      retrograde cholangio pancreatography (ERCP) is cannulation-induced spasm of the
      sphincter of Oddi and consequent pancreatic duct obstruction. Sublingual glyceryl
      trinitrate (GTN) has been shown to produce periampullary sphincter relaxation.
      The aim of this study was to determine whether prophylactic long-acting GTN could
      reduce the incidence of ERCP-induced pancreatitis. METHODS: In a randomized
      double-blind study, prophylactic treatment with GTN (2 mg given sublingually 5
      min before endoscopy) was compared with placebo in 186 patients who presented for
      elective ERCP. The primary endpoint was the occurrence of pancreatitis within 24
      h, defined as a serum amylase concentration greater than 1000 units/ml in
      association with a visual analogue pain score of more than 5. RESULTS: The
      incidence of pancreatitis was lower in the GTN group compared with placebo (seven
      of 90 versus 17 of 96; P < 0.05). Mean serum amylase values were similar in the
      two groups. The protective effect of GTN appears to be highest in the diagnostic
      ERCP group (one of 54 versus ten of 66; P = 0.012) and in the group in which
      cholangiography alone was performed (one of 54 versus eight of 57; P = 0.032).
      CONCLUSION: Prophylactic treatment with GTN reduces the incidence of pancreatitis
      following ERCP but does not seem to reduce the extent of hyperamylasaemia or the
      severity of pancreatitis.

PMID- 11531864
TI  - Randomized clinical trial comparing totally extraperitoneal inguinal hernia
      repair with the Shouldice technique.
AB  - BACKGROUND: The optimal technique for inguinal hernia repair remains contentious.
      This study compared the Shouldice repair with the totally extraperitoneal
      endoscopic (TEP) method in a randomized clinical trial, with quality of life
      (QoL) and cost analysis. METHODS: Two hundred patients were randomized to
      Shouldice or TEP repair. Patients were assessed after operation by questionnaire
      to determine operative outcomes, complications, QoL, and return to work and
      normal lifestyle. RESULTS: There were 117 TEP and 115 Shouldice repairs. Median
      operating time was longer for TEP repair (70 versus 56 min; P = 0.0001), but
      patients were discharged earlier (68 versus 48 per cent within 1 day; P =
      0.0065), and had a quicker return to work (14 versus 30 days; P = 0.0001) and
      normal lifestyle (21 versus 35 days; P = 0.0001). Open repair was nearly 40 per
      cent cheaper. Late follow-up in 171 patients (86 per cent) at a median of 1.3
      years found that TEP repair led to fewer complications at 1 year (9 versus 21 per
      cent; P = 0.05) and was associated with significant improvement for the QoL
      components of work performance and satisfaction, physical symptoms and sense of
      well-being. CONCLUSION: TEP repair results in fewer complications and an earlier
      return to work and normal lifestyle, but is more expensive and takes longer to
      perform.

PMID- 11531865
TI  - Expression of inducible nitric oxide synthase contributes to the development of
      pancreatitis following pancreatic ischaemia and reperfusion.
AB  - BACKGROUND: Inducible nitric oxide synthase (iNOS) activity is increased in
      experimentally induced acute pancreatitis. Increased expression of this isoform
      of nitric oxide synthase has been demonstrated in several organs subjected to
      ischaemia-reperfusion injury. The present experiment investigated the expression
      of iNOS and the effect of selective iNOS inhibition in pancreatic ischaemia
      reperfusion. METHODS: Wistar rats (n = 40) were randomly and equally assigned to
      four groups. Groups 2 and 4 underwent 60 min of total pancreatic ischaemia
      followed by 6 h of reperfusion (I-R). Groups 1 and 3 underwent sham operation.
      The selective iNOS inhibitor L-N(6)-(1-iminoethyl)-lysine (L-NIL) was
      administered to groups 3 and 4. Expression of iNOS was examined by
      immunohistochemistry. Other investigations included measurement of serum amylase
      activity and pancreatic wet : dry weight ratio, and histopathological
      examination. RESULTS: Eight of ten rats in group 2 (I-R only) expressed iNOS but
      none of the ten animals in group 1 (sham laparotomy) did so. Group 4 (I-R + L
      NIL) animals had significantly lower serum amylase levels and wet : dry weight
      ratios than those in group 2 (I-R only). Microscopic evidence of pancreatic
      injury was present only in rats in group 2 (I-R only). CONCLUSION: Expression of
      iNOS during reperfusion following pancreatic ischaemia contributes significantly
      to the development of acute pancreatitis.

PMID- 11531866
TI  - Liver transplantation for early-detected, multifocal hepatocellular carcinoma.

PMID- 11531867
TI  - Comparison of cardiac troponin I and creatine kinase ratios in the detection of
      myocardial injury after aortic surgery.
AB  - BACKGROUND: Perioperative myocardial infarction may not be diagnosed correctly
      because World Health Organization criteria are often not met and creatinine
      kinase myocardial fraction (creatinine kinase/creatinine kinase MB isoenzyme;
      CK/CK-MB) ratios can be difficult to interpret. Cardiac troponin (cTn) I and cTnT
      are the most sensitive and specific markers of myocardial cell necrosis currently
      available but are not widely used in surgical practice. The aim was to compare
      cTnI and CK/CK-MB ratios in the detection of myocardial injury following aortic
      surgery. METHODS: This was a prospective study of 59 patients undergoing elective
      (n = 28) or ruptured (n = 24) abdominal aortic aneurysm repair or elective
      aortofemoral bypass (n = 7). cTnI level was measured before operation and at 6,
      24 and 48 h after surgery. The CK/CK-MB ratio was measured where cTnI was
      detectable. RESULTS: Some 14 of 24 emergency and ten of 35 elective patients had
      detectable cTnI (greater than 0.5 ng/ml) at one or more time-points. The CK/CK-MB
      ratio was greater than 5 per cent in only four of 24 patients having an emergency
      operation and in none of the elective patients with detectable cTnI. CONCLUSION:
      Over half of patients undergoing emergency operation and more than a quarter of
      those having elective aortic surgery suffered myocardial necrosis as determined
      by detectable cTnI levels. This was accompanied by a raised CK/CK-MB ratio in
      less than one-fifth of patients.

PMID- 11531868
TI  - Preservation of endothelial integrity and function in experimental vascular
      anastomosis with non-penetrating clips.
AB  - BACKGROUND: Vascular repair with sutures is associated with disruption of the
      endothelial lining and subsequent thrombus formation on the intraluminal lesions.
      This experimental study was designed to determine whether the use of non
      penetrating clips improved endothelial preservation. METHODS: In ten female pigs,
      25-mm arteriotomies were made in both carotid arteries. The arteriotomies were
      repaired with jugular vein patches. On the left side, the repair was done with
      1.4-mm titanium clips, and on the right side with two running 6/0 polypropylene
      sutures. Next, the aorta was divided and subsequently repaired with 2-mm clips in
      five of these pigs, and with two running 5/0 polypropylene sutures in the
      remaining five pigs. Endothelial function was studied at the anastomotic site in
      the carotid arteries by determination of endothelium-dependent and -independent
      relaxatory responses. Morphometric examination of the carotid arteries and
      inspection of the aortic endothelium were performed by means of scanning electron
      microscopy. RESULTS: Maximal endothelium-dependent relaxation to adenosine 5'
      diphosphate was less in sutured than in clipped carotid arteries (P < 0.05),
      while there was no difference in maximal endothelium-independent relaxation to
      sodium nitrite. This result in clipped carotid arteries was not accompanied by
      less intimal hyperplasia. Screening of the aortic anastomotic line showed better
      preservation of endothelial architecture after clip anastomosis. Mean cross-clamp
      time for carotid patch repair was significantly less when using clips than with
      sutures. CONCLUSION: The use of non-penetrating clips for vascular anastomoses
      preserved endothelial function and structural integrity better than running
      sutures, although the degree of intimal hyperplasia was similar.

PMID- 11531869
TI  - Preserved endothelial integrity and nitric oxide synthase in saphenous vein
      grafts harvested by a 'no-touch' technique.
AB  - BACKGROUND: The saphenous vein is the most commonly used conduit for coronary
      artery bypass surgery, but 1-year occlusion rates as high as 30 per cent have
      been reported. In conventional surgery, considerable damage to the vein occurs
      during harvesting. The aim of this study was to compare endothelial integrity and
      nitric oxide synthase (NOS) in saphenous veins harvested by a novel 'no-touch'
      technique and veins harvested conventionally. METHODS: Immunohistochemistry was
      used to study endothelial integrity, and a combination of histochemistry and
      autoradiography was employed to identify NOS in human saphenous veins harvested
      by conventional and no-touch techniques. RESULTS: The endothelial lining of
      conventional grafts was reduced compared with that of no-touch grafts (52 versus
      73 per cent; P = 0.04). This was associated with a concomitant reduction of NOS
      availability; NOS was also present in the adventitial vasa vasorum of no-touch
      vessels. CONCLUSION: Some of the sites with potential for nitric oxide release in
      vivo are removed during conventional saphenous vein harvesting. These sites were
      preserved after no-touch harvesting, suggesting the potential to improve coronary
      artery bypass graft patency.

PMID- 11531870
TI  - Quality of life after low anterior resection with total mesorectal excision and
      temporary loop ileostomy for rectal carcinoma.
AB  - BACKGROUND: Low anterior resection (LAR) with total mesorectal excision (TME) may
      be the optimal operation for carcinoma of the mid or lower rectum. Routine
      formation of a temporary defunctioning stoma has been recommended with TME. The
      impact of this strategy on health-related quality of life (HRQOL) has not been
      addressed. METHODS: A prospective longitudinal study was conducted among 24
      patients undergoing LAR with TME and loop ileostomy for rectal cancer. Clinical
      outcomes were documented. HRQOL was assessed using Short Form 36 (SF-36). Twenty
      three patients undergoing high anterior resection (HAR) for rectosigmoid cancer
      were studied concurrently to determine the effects of major colorectal resection
      without a stoma. RESULTS: Time to resume normal diet, length of stay in hospital
      and time to return to non-work activities were similar after HAR or LAR with TME
      and loop ileostomy. Twelve weeks after HAR SF-36 scores were stable or improved
      compared with preoperative levels. In contrast, 12 weeks after LAR + TME patients
      had a reduction in physical functioning scores on SF-36. SF-36 scores improved
      after ileostomy closure. Ileostomy closure increased total hospital stay and time
      off non-work activities. CONCLUSION: LAR with TME and temporary loop ileostomy
      for rectal cancer results in a long total hospital stay and impairs aspects of
      HRQOL. Prompt stoma closure should be a priority in these patients.

PMID- 11531871
TI  - Population-based study of factors influencing occurrence and prognosis of local
      recurrence after surgery for rectal cancer.
AB  - BACKGROUND: Few data are available from population-based statistics on the risk
      of local recurrence after surgery for rectal cancer. The aims of this study were
      to determine factors influencing local control and to analyse treatment and
      prognosis of recurrences in a well defined population. METHODS: Data were
      obtained from the cancer registry of the Cote d'Or (France). From 1976 to 1995,
      682 patients resected for cure for a rectal carcinoma were included. Recurrence
      rates and survival rates were calculated using actuarial methods. A relative
      survival analysis and Cox multivariate analysis were performed. RESULTS: During
      the study 135 local recurrences were registered. The 5-year cumulative local
      recurrence rate was 22.7 per cent. In multivariate analysis the two variables
      significantly associated with local recurrence risk were stage at diagnosis and
      the macroscopic type of growth. There was a non-significant decrease in local
      recurrence rate in patients treated by preoperative radiotherapy compared with
      that in patients treated by surgery alone. The proportion of patients re-resected
      for cure was 25.2 per cent, and increased from 13.0 per cent in 1976-1985 to 37.9
      per cent in 1986-1995 (P = 0.001). The 5-year relative survival rate was 13.6 per
      cent overall and 40.6 per cent after resection for cure (P < 0.001). CONCLUSION:
      Local recurrence of rectal cancer following resection remains a substantial
      problem. Improvement can be expected from better care and earlier diagnosis.

PMID- 11531872
TI  - Patient accuracy of reporting on hereditary non-polyposis colorectal cancer
      related malignancy in family members.
AB  - BACKGROUND: The cancer family history is important in identifying individuals
      with hereditary non-polyposis colorectal cancer (HNPCC). The accuracy of a
      suspected HNPCC family history reported by patients with colorectal cancer was
      evaluated. METHODS: This was a prospective population-based study including
      consecutive patients with colorectal cancer. A questionnaire covering the
      occurrence of malignancy among relatives was completed. RESULTS: A total of 1200
      patients with colorectal cancer completed the questionnaire. Fulfilment of
      Amsterdam criteria I or II according to the patients' reports was rejected in
      three of 14 cases (false-positive rate 21 per cent). Furthermore, seven of 18
      probands whose families met the Amsterdam criteria I or II after verification
      were identified by further exploration in families who, according to the
      probands, met weaker criteria (false-negative rate 39 per cent). CONCLUSION: The
      present study suggests that family studies on HNPCC are not reliable unless the
      diagnoses of family members are verified from official sources. If endoscopic
      screening is offered entirely on the basis of unverified information from
      patients with colorectal cancer, there is a risk that a large proportion of the
      families will not be offered relevant surveillance.

PMID- 11531873
TI  - Diagnosis and prognosis of breast cancer by magnetic resonance spectroscopy of
      fine-needle aspirates analysed using a statistical classification strategy.
AB  - BACKGROUND: The aim was to develop robust classifiers to analyse magnetic
      resonance spectroscopy (MRS) data of fine-needle aspirates taken from breast
      tumours. The resulting data could provide computerized, classification-based
      diagnosis and prognostic indicators. METHODS: Fine-needle aspirate biopsies
      obtained at the time of surgery for both benign and malignant breast diseases
      were analysed by one-dimensional proton MRS at 8.5 Tesla. Diagnostic correlation
      was performed between the spectra and standard pathology reports, including the
      presence of vascular invasion by the primary cancer and involvement of the
      excised axillary lymph nodes. RESULTS: Malignant tissue was distinguished from
      benign lesions with an overall accuracy of 93 per cent. From the same spectra,
      lymph node involvement was predicted with an overall accuracy of 95 per cent, and
      tumour vascular invasion with an overall accuracy of 94 per cent. CONCLUSION: The
      pathology, nodal involvement and tumour vascular invasion were predicted by
      computerized statistical classification of the proton MRS spectrum from a fine
      needle aspirate biopsy taken from the primary breast lesion.

PMID- 11531874
TI  - Pattern of cervical lymph node metastases from papillary carcinoma of the
      thyroid.
AB  - INTRODUCTION: The management of cervical metastases from papillary thyroid
      carcinoma ranges from selective removal (berry picking) to a formal comprehensive
      neck dissection. Without a clear understanding of the distribution of nodes at
      risk, the formulation of strategies on how best to manage the clinically positive
      neck is difficult. This study reports on observations made in patients who
      underwent a therapeutic comprehensive neck dissection for metastatic papillary
      thyroid carcinoma by defining lymph node involvement with respect to neck level.
      METHODS: The clinical records and pathological reports of 75 consecutive patients
      who underwent a neck dissection for cervical metastases from papillary thyroid
      carcinoma over a 10-year period were reviewed. All dissections were therapeutic
      in nature, being performed in patients with clinically positive neck nodes.
      Eighty neck dissection specimens were obtained and analyses were divided into
      three groups by virtue of the type of dissection performed: a bilateral
      comprehensive neck dissection, unilateral radical neck dissection and unilateral
      comprehensive neck dissection. The relative involvement of cervical nodes was
      analysed with reference to node levels I-V. RESULTS: Patients in the
      anterolateral group (levels II, III and IV) were at greatest risk of metastatic
      disease, with level III nodes consistently the most frequently involved, across
      all treatment groups. Only three patients exhibited level I involvement, all of
      whom had extensive neck disease involving all or almost all neck levels.
      CONCLUSION: The majority of patients present with multiple level node disease,
      with the anterolateral group at greatest risk. A comprehensive neck dissection is
      recommended for all patients with palpable cervical lymphadenopathy.

PMID- 11531875
TI  - Intragastric balloon in the treatment of patients with morbid obesity.
AB  - BACKGROUND: Morbid obesity is a major health problem. This study evaluated the
      effectiveness and safety of an intragastric balloon (IGB) for the treatment of
      morbid obesity. METHODS: Sixty-nine IGBs were inserted endoscopically over a 3
      year period in 63 consecutive patients (59 women; median age 41 (range 24-67)
      years). Median weight and body mass index were 124.5 (range 89.0-177.8) kg and
      46.3 (range 36.2-72.4) kg/m(2) respectively. Significant coexistent disease was
      present in 34 patients. Median American Society of Anesthesiologists score was 3
      (range 1-4). Data were recorded following retrospective review of patient case
      notes. RESULTS: Mean operating time was 22 (range 15-30) min and median inpatient
      stay was 1 (range 1-6) day. Vomiting was the commonest early complication
      following 31 procedures and necessitated early removal of four IGBs. Of 58
      patients with long-term follow-up, 18 suffered displacement of the IGB after at
      least 6 months in situ and three required a laparotomy for intestinal
      obstruction. Fifty patients (86 per cent) lost weight; median weight loss was
      15.0 kg (P < 0.001). Median excess weight loss was 16.4 (range - 49.0 to + 4.8)
      and 18.7 (range - 51.5 to 12.6) per cent by 4 and 7 months after IGB insertion
      respectively. CONCLUSION: The IGB represents a useful device for the treatment of
      morbid obesity, particularly in preparation for definitive antiobesity
      procedures. Early IGB replacement is essential to minimize complications.

PMID- 11531876
TI  - Epidemiological study of oesophageal and gastric cancer in south-east England.
AB  - BACKGROUND: This epidemiological study was carried out to establish the magnitude
      of the changing incidence of gastric and oesophageal cancer. METHODS: Time-trend
      analyses of subsite-specific cancers of the oesophagus and stomach were performed
      using data from the Thames Cancer Registry database (1960-1996) for the South
      Thames Region. The changes in sex ratio and peak age of incidence are reported.
      RESULTS: In the upper two-thirds of the oesophagus there was no significant
      change in the incidence rate, but the lower third of the oesophagus showed a
      marked rise for both sexes (average annual change + 0.05 for men, + 0.009 for
      women). For the gastric cardia, the incidence in males increased (average annual
      change + 0.025), while in females it remained unchanged. Cancers of the
      oesophagogastric junction showed a clear increase for both sexes (average annual
      change + 0.07 for men, + 0.009 for women). There were changes in the sex ratio
      and peak age of incidence for all subsite cancers for both sexes. CONCLUSION:
      Over a 37-year period the incidence of cancer of the oesophagogastric junction
      increased threefold, while the incidence of cancers of the other subsites of the
      stomach decreased. Further studies are needed to investigate the aetiology of
      these changes.

PMID- 11531877
TI  - Glove powder promotes adhesion formation and facilitates tumour cell adhesion and
      growth.
AB  - BACKGROUND: The presence of foreign material in the abdominal cavity irritates
      the peritoneal surface, leading to an inflammatory response. This defensive
      mechanism can provoke adhesion formation. The same peritoneal defence cascade is
      thought to play a role in the process of intra-abdominal tumour recurrence. The
      aim of this study was to evaluate whether glove powder produced peritoneal
      adhesions in a rat adhesion model and whether it promoted intra-abdominal tumour
      recurrence in a rat tumour cell adhesion and growth model. METHODS: A
      reproducible model that allowed semiquantitative scoring of adhesion formation or
      tumour load was used in three different groups of rats. One group was treated by
      intra-abdominal application of powder obtained from starch-powdered gloves, one
      by application of pure starch and in one group no powder was used. RESULTS:
      Application of glove powder or pure starch on minimally and severely traumatized
      peritoneum gave rise to significantly greater adhesion formation and intra
      abdominal tumour load than peritoneal trauma alone (both P < 0.001). CONCLUSION:
      Starch-induced peritoneal trauma leads not only to more adhesion formation but
      also to increased adhesion and growth of tumour cells. Since good powder-free
      alternatives are available there is no longer any justification for the use of
      powdered gloves during intra-abdominal surgery.

PMID- 11531878
TI  - Rectal adenocarcinoma with liver metastases: management of the primary tumour (Br
      J Surg 2001; 88: 163-4).

PMID- 11531880
TI  - Single-blind randomized clinical trial of laparoscopic versus open appendicectomy
      in children (Br J Surg 2001; 88: 510-14).

PMID- 11531882
TI  - Variation in clinical decision making is a partial explanation for geographical
      variation in lower extremity amputation rates (Br J Surg 2001; 88: 529-33).

PMID- 11531884
TI  - Outcome and late functional results after anastomotic leakage following
      mesorectal excision for rectal cancer (Br J Surg 2001; 88: 400-4).

PMID- 11531886
TI  - Randomized clinical trial of local bupivacaine perfusion versus parenteral
      morphine infusion for pain relief after laparotomy (Br J Surg 2001; 88: 357-9).
      Letter 2.

PMID- 11531888
TI  - Review of current practice to establish success after vasectomy (Br J Surg 2001;
      88: 290-3).

PMID- 11531889
TI  - Randomized clinical trial of local bupivacaine perfusion versus parenteral
      morphine infusion for pain relief after laparotomy (Br J Surg 2001; 88: 357-9).
      Letter 1.

PMID- 11531891
TI  - Revisiting transtibial amputation with the long posterior flap (Br J Surg 2001;
      88: 683-6).

PMID- 11531894
TI  - Migraine and haemostasis.
AB  - Migraine is a risk factor for cerebral infarction in young women. The nature of
      the connection between these diseases remains however essentially unknown.
      Abnormalities of haemostasis leading to an increased thrombotic risk would
      provide a logical link. Platelets, antiphospholipid antibodies and more recently
      congenital thrombophilia have thus successively been implicated. The different
      studies concerning these topics have been reviewed. Because of the conflicting
      results obtained and because of the numerous methodological shortcomings of many
      of these studies, no definite conclusion can be reached. It is possible that
      these 3 factors play a role in the ischemic risk of migraine, but it is as likely
      or even more likely that other factors (inside or outside the hemostatic system)
      play a more important role. Further studies are thus deeply needed.

PMID- 11531895
TI  - Needle acupuncture in tension-type headache: a randomized, placebo-controlled
      study.
AB  - A study with needle acupuncture was performed in tension-type headache employing
      a new placebo acupuncture METHOD: Sixty-nine patients (mean age 48.1 years, SD =
      14.1) fulfilling the International Headache Society criteria for tension-type
      headache were randomly assigned to verum or placebo condition. No significant
      differences between placebo and verum with respect to visual analogue scale and
      frequency of headache attacks could be observed immediately, 6 weeks and 5 months
      after the end of treatment. There was a significant but weak improvement in
      quality of life parameters (clinical global impressions, Nottingham Health
      Profile) after verum treatment. In decision tree analyses, the changes in
      clinical global impressions and headache frequency depended significantly on
      primary headache frequency with a limit value of 24.5 days headache per month.
      High values in the von Zerssen Depression Score resulted in high mean visual
      analogue scale values.

PMID- 11531896
TI  - Nitric oxide potentiates response of trigeminal neurones to dural or facial
      stimulation in the rat.
AB  - Infusing glyceryl trinitrate as a donor molecule, we have used
      electrophysiological and c-fos immunostaining techniques to study the effects of
      nitric oxide on neurones in the nucleus trigeminalis caudalis. Following infusion
      of glyceryl trinitrate, responses of neurones to electrical stimulation of
      periorbital cutaneous afferents were potentiated and threshold for activation of
      neurones by stimulation of dural afferents was reduced. Expression of c-fos was
      unchanged by glyceryl trinitrate compared to saline controls. Intradermal
      injection of capsaicin in the periorbital area increased c-fos expression in
      nucleus trigeminalis caudalis; this was significantly potentiated by glyceryl
      trinitrate. These results suggest that, in the anaesthetized rat, glyceryl
      trinitrate alone may not acutely activate the trigeminovascular system to a
      significant degree at doses that cause headache and later trigger migraine
      headache in migraineurs. Nevertheless, it is susceptible to exogenous nitric
      oxide in that activation of trigeminal neurones through cutaneous or dural
      pathways is potentiated. This may in some measure underlie the pathogenesis of
      migraine headache.

PMID- 11531897
TI  - The lack of vasoconstrictor effect of the pineal hormone melatonin in an animal
      model predictive of antimigraine activity.
AB  - The pineal hormone, melatonin, has been implicated in the pathophysiology of
      migraine and several studies have demonstrated its vasoconstrictor properties. In
      the present study, systemic and carotid haemodynamic effects of melatonin,
      administered directly into the carotid artery, were investigated in anaesthetized
      pigs. Ten-minute intracarotid infusions of melatonin (1, 10 and 100 microg kg(-1)
      min(-1)) produced slight decreases in blood pressure and total carotid and
      arteriovenous anastomotic blood flows, but nutrient blood flow was not affected.
      The decrease in carotid blood flow was entirely caused by the hypotension, since
      no changes in vascular conductance values were observed. It is concluded that
      melatonin itself is not capable of producing vasoconstriction in the cranial
      circulation of anaesthetized pigs. Thus, it appears that melatonin has no anti
      migraine potential via a vasoconstrictor mechanism.

PMID- 11531898
TI  - One-year prevalence of migraine in Sweden: a population-based study in adults.
AB  - A randomly selected sample of 1668 individuals (782 women and 886 men) aged 18-74
      years was interviewed by telephone using a standardized questionnaire including
      the International Headache Society (IHS) criteria for migraine. The survey was
      performed by SIFO, the national public opinion poll agency. The results obtained
      demonstrate that 21% of the Swedish population had suffered from severe headaches
      during the past year. A majority of these headache sufferers (61%) fulfilled the
      IHS-criteria for migraine. The 1-year prevalence of migraine in Sweden was found
      to be 13.2 +/- 1.9% (16.7% among women and 9.5% among men). The prevalence of
      migraine in this Swedish population did not differ between the northern, middle
      and southern part of Sweden, or between urban and rural areas or different income
      groups. Only about half (49%) of the migraineurs had been diagnosed by a
      physician. Among the individuals who fulfilled the IHS criteria for migraine the
      mean attack-frequency was 1.3 per month and the mean attack-duration was 19 h. If
      the duration of the attack was disregarded as a strict criterion for migraine
      (attacks < 4 h and > 72 h were included), the prevalence increased to 17.0 +/-
      1.9% without affecting the sex distribution. With this amendment, 92% of those
      who considered their headaches to be migraine or migraine-like in fact fulfilled
      the alternative criteria for migraine. However, only 76% of those who believed
      that they had migraine or migraine-like headaches fulfilled the strict IHS
      criteria for migraine. An extension of the time window from 4 to 72 h may be
      reasonable both from a pragmatic and from a rational clinical point of view.

PMID- 11531899
TI  - The efficacy and safety of sc alniditan vs. sc sumatriptan in the acute treatment
      of migraine: a randomized, double-blind, placebo-controlled trial.
AB  - This double-blind, placebo-controlled, parallel-group, multicentre,
      multinational, phase-III trial was designed to assess the efficacy and safety of
      a single subcutaneous injection of placebo, 2 doses of alniditan (1.4 mg and 1.8
      mg) and 6 mg of sumatriptan in subjects with acute migraine. A total of 114
      investigators from 13 different countries screened 2021 subjects. In total 924
      patients were treated with placebo (157), alniditan 1.4 mg (309), alniditan 1.8
      mg (141) and sumatriptan 6 mg (317). The lower number of subjects in the
      alniditan 1.8 mg group is due to the termination of this trial arm after the
      incidence of a serious adverse event and a subsequent protocol amendment. The
      number of subjects who were pain free at 2 h (primary endpoint) was: 22 (14.1%)
      with placebo, 174 (56.3%) with alniditan 1.4 mg, 87 (61.7%) with alnditan 1.8 mg
      and 209 (65.9%) with sumatriptan 6 mg. Alniditan 1.4 mg was significantly better
      (P < 0.001) than placebo and sumatriptan was significantly better (P = 0.015)
      than alniditan 1.4 mg. The number of responders (reduction of headache severity
      from moderate or severe headache before treatment to mild or absent at 2 h), was
      59 (37.8%) on placebo, 250 (80.9%) on alniditan 1.4 mg, 120 (85.1%) on alniditan
      1.8 mg, and 276 (87.1%) on sumatriptan. Response was significantly higher (P <
      0.001) with alniditan 1.4 mg than with placebo, and significantly lower (P =
      0.036) with alniditan 1.4 mg than with sumatriptan. Recurrence rates were: 22
      (37.3%) with placebo, 87 (34.8%) with alniditan 1.4 mg, 35 (29.2%) with alniditan
      1.8 mg and 108 (39.1%) with sumatriptan. Adverse events occurred in 577/924
      (62.4%) subjects, i.e. in 62/157 (39.5%) with placebo, 214/309 (69.3%) with
      alniditan 1.4 mg, 91/141 (64.5%) with alniditan 1.8 mg and 210/317 (66.2%) with
      sumatriptan 6 mg. Sumatriptan was significantly better than alniditan 1.4 mg for
      pain free at 2 h. The difference, however, was small and clinically not
      important. For alniditan, a dose-dependent adverse event relationship was seen.
      The safety profile of alniditan 1.4 mg was similar to that of sumatriptan.

PMID- 11531900
TI  - An open preference study with sumatriptan 50 mg and zolmitriptan 2.5 mg in 100
      migraine patients.
AB  - Understanding factors influencing patients' preference will improve guidance to
      make rational choices in expanded symptomatic migraine treatment. The objective
      of this open-label, cross-over study was to explore patients' preferences for
      sumatriptan 50 mg vs. zolmitriptan 2.5 mg tablets, focusing on factors
      influencing this preference. One hundred consecutive migraine patients attending
      our clinics were asked to treat three attacks with each medication and then fill
      out a preference questionnaire. Ninety-four migraineurs completed the trial and
      42 (44%, 95% CI 34-58%) reported that they preferred zolmitriptan 2.5 mg over
      sumatriptan 50 mg tablets and 27 (29%, 20-38%) preferred sumatriptan 50 mg. The
      remaining 25 (27%, 18-36%) did not show any preference. For the initial treatment
      of the attacks, there were more patients needing just one tablet of zolmitriptan
      2.5 mg compared with sumatriptan 50 mg (67 vs. 39%). The reasons for preference
      among those 69 patients who had shown preference for either of the two triptans
      were: a faster onset of action (speed of onset) (73%), a longer duration of the
      effects (39%), fewer adverse events (35%) and lower price (13%). Only one-quarter
      of the studied migraine population thought that sumatriptan 50 mg and
      zolmitriptan 2.5 mg were equivalent, which suggests that most migraine patients
      differentiate between triptans. A faster onset of action (speed of onset) was the
      most important reason for preference.

PMID- 11531901
TI  - Sferics and headache: a prospective study.
AB  - Sferics are low frequency, low intensity electromagnetic pulses radiating from
      distant meteorological events and other yet unknown sources. It has been
      hypothesized that sferics are part of the purported sensitivity to weather
      changes reported by headache sufferers. We tested this proposal. Patients
      (migraine and/or tension headache) enrolled in a randomized clinical trial gave
      daily headache data (intensity, frequency, duration of headache) for at least 18
      weeks. Concurrently, a sferics measurement station in the vicinity of the
      patients recorded frequency and intensity of sferics. Usable headache data from
      21 patients and the corresponding sferics series were subjected to time series
      analysis applying ARIMA models and then cross-correlated. We found significant
      and consistent cross-correlations of moderate size at lag 0 in one patient
      between ARIMA-filtered headache intensity and frequency (r = 0.18) and amplitude
      of sferics (r = 0.20). We conclude that in an unselected sample of headache
      patients some may indeed be susceptible to the low intensity type of
      electromagnetic radiation exemplified by sferics pulses. This phenomenon warrants
      further scrutiny.

PMID- 11531902
TI  - Are there predictive factors for long-term outcome after withdrawal in drug
      induced chronic daily headache?
AB  - OBJECTIVES: To investigate prognostic factors for long-term outcome of patients
      after inpatient withdrawal because of drug-induced chronic daily headache.
      PROCEDURES: Fifty-five patients (36 females) were re-examined by means of a
      standardized interview after inpatient withdrawal. The mean observation period
      was 9.28 +/- 2.85 years (mean +/- SD; median 8.58; range 5.00-13.50). RESULTS:
      Five years after withdrawal, one-third of the patients (34.6%) had an overall
      favourable outcome, one-third (32.7%) had no recurrent drug overuse and reported
      a clear-cut improvement of headache, and one-third (32.7%) developed recurrent
      drug overuse. Most relapses occurred within 2 years, and a small percentage
      within 5 years. No predictors for long-term outcome after inpatient withdrawal
      were found. CONCLUSIONS: All patients with drug-induced chronic daily headache
      should be considered as good candidates for inpatient withdrawal, and no patient
      should be excluded from that therapy.

PMID- 11531903
TI  - Primary yawning headache.
AB  - To describe three patients with recurrent severe paroxysmal headache precipitated
      by yawning. Pain elicited by yawning is a well-recognized clinical phenomenon in
      patients with cranial neuralgia, temporomandibular joint dysfunction syndrome and
      Eagle syndrome. Clinical history, neurological and oral examinations, brain
      magnetic resonance imaging (MRI), cranial nerve electrophysiological testing and
      skull X-rays are reported. In all the patients pain was induced by yawning; in
      the third patient pain was also triggered by eructation. None had history of
      migraine. Facial gestures and forceful opening of the mouth did not reproduce the
      pain. The first patient had retroauricular pain, simvastatin-induced myopathy and
      subclinical axonal peripheral neuropathy; the second patient had a post-viral
      benign sensory neuropathy; and the third had retroauricular and facial pain and
      no underlying neurological illness. Cranial nerve testing and MRI of the brain
      were normal except for a coincidentally found pituitary adenoma on the first
      patient. Headache or cranial pain with yawning may occur in patients with no
      apparent cause (primary yawning headache). It is a chronic, benign condition that
      requires no specific treatment but needs to be distinguished from secondary
      yawning headache, of greater clinical relevance.

PMID- 11531904
TI  - Sumatriptan overdose in episodic cluster headache: a case report of overuse
      without event.

PMID- 11531905
TI  - SUNCT syndrome: the first case in childhood. Short-lasting unilateral
      neuralgiform headache attacks with conjunctival injection and tearing.

PMID- 11531906
TI  - Recurrent subdural haematomas in a patient with spontaneous intracranial
      hypotension.

PMID- 11531907
TI  - Parkinson's and migraine.

PMID- 11531909
TI  - Opioid chronopharmacology.

PMID- 11531911
TI  - Children: whose problem? - An editorial.

PMID- 11531912
TI  - Prevalence and morbidity associated with non-malignant, life-threatening
      conditions in childhood.
AB  - OBJECTIVE: To determine the prevalence of non-malignant life-threatening illness
      in childhood and associated morbidity in the affected child and their family
      members. DESIGN: Cross-sectional survey. SETTING: Bath Clinical Area (total
      population 411,800). SUBJECTS: Children aged 0-19 years. RESULTS: One hundred and
      twenty-three children were identified, giving a prevalence of 1.2/1000 children.
      Morbidity assessed in 93 children showed 60% in pain or discomfort, 35% unable to
      walk and 25% with severe cognitive impairment. Mental health problems were found
      in 54% of mothers and 30% of fathers, and significant emotional and behavioural
      problems in 24% of healthy siblings. CONCLUSIONS: Non-malignant life-threatening
      illness is more prevalent than reported in previous studies. Considerable
      morbidity is experienced by the child and their family. An individual and family
      approach is required. Key messages (1) The prevalence of non-malignant life
      threatening illness is four times greater than previous estimates. (2) This group
      of conditions have significant implications for all family members. (3) Early
      comprehensive assessment and access to effective interventions may pre-empt later
      problems.

PMID- 11531913
TI  - Clumsiness, dyspraxia and developmental co-ordination disorder: how do health and
      educational professionals in the UK define the terms?
AB  - At the turn of the century, the idea that there might be a discrete childhood
      syndrome, which had 'clumsiness' of movement as its defining symptom, began to
      emerge. Since then numerous labels have been applied to the syndrome. In spite of
      recent attempts to standardise the terminology used, variation continues to
      compromise inter-professional communication and interpretation of research. The
      aim of this study was to determine how the three terms 'Clumsy', 'Dyspraxia' and
      'Developmental Co-ordination Disorder (DCD)' are viewed by health and educational
      professionals in the UK. Two hundred and thirty-four adults (57% from the health
      professions and 43% from education) provided a written definition of each term.
      Content analysis of the 702 definitions was used to determine: (1) the extent to
      which the terms were familiar/acceptable to the respondents; and (2) to capture
      differences in the meaning of the term being defined. The results indicated that
      the terms 'DCD' and 'Dyspraxia' were less familiar than the term 'clumsy' which
      was, however, least acceptable. Amongst those professionals who were familiar
      with all three terms, there was general agreement that all were used to describe
      some sort of overall movement difficulty. Beyond that point, divergence of
      understanding and inter-professional differences in emphasis emerged. The
      implications of these differences for clinical and educational practice, research
      and policy making are discussed.

PMID- 11531914
TI  - Severity of hyperactivity and the comorbidity of hyperactivity with clumsiness in
      three sample sources: school, support group and hospital.
AB  - The aim of this study was to examine whether or not there were any differences in
      the severity of hyperactivity and the comorbidity of hyperactivity with
      clumsiness due to the sampling sources of hyperactive children. It was
      hypothesized that hyperactivity would be more severe and the comorbidity higher
      in the hospital sample than in the community support group and the school sample.
      A total of 47 hyperactive children were assessed with the German version of the
      Conners Teacher Rating Scale (CTRS) and the Movement Assessment Battery for
      Children (Movement ABC). The hypotheses were not supported by the results.
      Although the school sample demonstrated the least prevalence rate of comorbid
      clumsiness, their conduct problems were rated higher than were the hospital and
      the support group samples. The possible difference in teachers' perception was
      discussed in terms of their understanding and communication with parents and
      professionals. The need to determine the effect of inattention on manual
      performance is addressed with a research strategy.

PMID- 11531915
TI  - Integration of children with visual impairment in regular preschools.
AB  - The current practice in Germany is to integrate children who are blind or
      partially sighted into regular preschools providing they exhibit no further
      severe impairments. The present study asked 72 regular preschool teachers about
      their experiences in integrating 24 children who were blind and 16 who were
      partially sighted. Results showed that integration seemed to be unproblematic
      except for greater emotional difficulties in children who are partially sighted.
      According to preschool teachers, integrating children who are blind is far more
      complex and difficult than integrating the partially sighted. One fifth of the
      blind exhibited marked to serious problems in 10 out of 28 preschool activities
      surveyed. Most of these difficulties involved manual, cognitive, interactive and
      daily living skills. When asked about difficulties that had not been anticipated
      before integration commenced, preschool teachers emphasized four domains: the
      increase in their own workload; the children's problems with concentration and
      motivation; fixation on one preschool teacher; and difficulties in the fine- and
      gross-motor domain as well as in daily living skills. Findings indicate the need
      for improved preparations and support when integrating the blind into regular
      preschool.

PMID- 11531916
TI  - Knowledge and attitudes in multicultural health care.
AB  - Health professionals' knowledge of ethnic minority cultures and lifestyles was
      assessed to determine whether the respondents' cultural background and experience
      of working with ethnic minorities affected the health care delivered by them and
      to assess the need for training. Improving access to health services for ethnic
      minorities requires continuing education and training of all health
      professionals.

PMID- 11531917
TI  - 'What is it?': findings on preschoolers' responses to play with medical
      equipment.
AB  - When young people enter a hospital they are exposed to a foreign world of
      unfamiliar people, medical equipment and language. Children diagnosed with
      leukaemia are particularly vulnerable to repeated exposure to these distressing
      hospital visits. Assessing a child's understanding of the stresses associated
      with treatment during hospitalization is now seen as a key element of caring for
      the paediatric patient. A population particularly vulnerable to the effects of
      the stress of intensive treatments during hospitalization are preschool children.
      In order to understand the impact on leukaemia preschool children of intensive
      hospital treatment it is necessary to have comparative information on healthy
      peers who have not been exposed to such treatment experiences. This article
      presents findings from recent qualitative research that explored the beliefs held
      by healthy preschoolers about what happens in hospital, what it means to be sick,
      their reactions to and knowledge of medical equipment and their level of
      knowledge regarding cancer and leukaemia. It is the hope and expectation that the
      findings will be used comparatively to contribute to a deeper understanding of
      the world of the child coping with leukaemia and related disorders.

PMID- 11531919
TI  - Somatic and germline mutations of the TSH receptor and thyroid diseases.

PMID- 11531920
TI  - The genetics of IHH--a paradox.

PMID- 11531921
TI  - Release of leptin and its effect on hormone release from human pituitary
      adenomas.

PMID- 11531922
TI  - Idiopathic gonadotrophin deficiency: genetic questions addressed through
      phenotypic characterization.
AB  - OBJECTIVE: The association of idiopathic hypogonadotrophic hypogonadism (IHH)
      with congenital olfactory deficit defines Kallmann's syndrome (KS). Although a
      small proportion of IHH patients have been found to harbour defined genetic
      lesions, the genetic basis of most IHH cases remains to be elucidated. Genes
      currently recognized to be involved comprise KAL (associated with X-linked-KS),
      the GnRH receptor (associated with resistance to GnRH therapy), DAX 1 (associated
      with adrenohypoplasia congenita) and three loci also associated with obesity,
      leptin (OB), leptin receptor (DB) and prohormone convertase (PC1). Because of the
      rarity of the condition and the observation that patients are almost universally
      infertile without assistance, familial transmission of IHH is encountered
      infrequently and pedigrees tend to be small. This has constrained the ability of
      conventional linkage studies to identify other candidate loci for genetic IHH. We
      hypothesized that a systematic clinical evaluation of a large patient sample
      might provide new insights into the genetics of this rare disorder. Specifically,
      we wished to examine the following propositions. First, whether normosmic (nIHH)
      and anosmic (KS) forms of IHH were likely to be genetically discrete entities, on
      the basis of quantitative olfactory testing, analysis of autosomal pedigrees and
      the prevalence of developmental defects such as cryptorchidism and cleft palate.
      Second, whether mirror movements and/or unilateral renal agenesis were specific
      phenotypic markers for X-linked-KS. DESIGN AND PATIENTS: We conducted a clinical
      study of 170 male and 45 female IHH patients attending the endocrinology
      departments of three London University teaching hospitals. Approximately 80% of
      data were obtained from case records and 20% collected prospectively. Parameters
      assessed included olfaction, testicular volume, family history of hypogonadism,
      anosmia or pubertal delay, and history or presence of testicular maldescent,
      neurological, renal or craniofacial anomalies. Where possible, the clinical
      information was correlated with published data on genetic analysis of the KAL
      locus. RESULTS: Olfactory acuity was bimodally distributed with no evidence for a
      spectrum of olfactory deficit. Testicular volume, a marker of integrated
      gonadotrophin secretion, did not differ significantly between anosmic and
      normosmic patients, at 2.0 ml and 2.2 ml, respectively. Nevertheless, the
      prevalence of cryptorchidism was nearly three times greater in anosmic (70.3%, of
      which 75.0% bilateral) than in normosmic (23.2%, of which 43.8% bilateral)
      patients. Individuals with nIHH, eugonadal isolated anosmia and/or KS were
      observed to coexist within 6/13 autosomal IHH pedigrees. On three occasions,
      fertility treatment given to an IHH patient had resulted in the condition being
      transmitted to the resulting offspring. Mirror movements and unilateral renal
      agenesis were observed in 24/98 and 9/87 IHH patients, respectively, all of whom
      were identifiable as X-KS males on the basis of pedigree analysis and/or
      defective KAL coding sequence. Abnormalities of eye movement and unilateral
      sensorineural deafness were observed in 10/21 and 6/111 KS patients,
      respectively, but not in nIHH patients. DISCUSSION: Patients with IHH are almost
      invariably either anosmic (KS) or normosmic (nIHH), rather than exhibiting
      intermediate degrees of olfactory deficit. Moreover, the prevalence of
      cryptorchidism is nearly three times greater in KS than in nIHH despite
      comparable testicular volumes, suggesting a primary defect of testicular descent
      in KS independent of gonadotrophin deficiency. Disorders of eye movement and
      hearing appear only to occur in association with KS. Taken together, these
      findings indicate a clear phenotypic separation between KS and nIHH. However,
      pedigree studies suggest that autosomal KS is an heterogeneous condition, with
      incomplete phenotypic penetrance within pedigrees, and that some cases of
      autosomal KS, nIHH and even isolated anosmia are likely to have a common genetic
      basis. The prevalences of anosmia, mirror movements and unilateral renal agenesis
      among X-KS men are estimated to be 100, 85 and 31%, respectively. In sporadic
      IHH, mirror movements and unilateral renal agenesis are 100% specific phenotypic
      markers of de novo X-KS. By comparison, only 7/10 X-KS families harboured KAL
      coding defects. Clinical ascertainment, using mirror movements, renal agenesis
      and ichthyosis as X-KS-specific phenotypic markers, suggested that de novo X-KS
      was unlikely to comprise more than 11% of sporadic cases. The majority of
      sporadic KS cases are therefore presumed to have an autosomal basis and, hence,
      the preponderance of affected KS males over females remains unexplained, though
      reduced penetrance in women would be a possibility.

PMID- 11531923
TI  - Bone metabolism and body composition in Japanese patients with active acromegaly.
AB  - OBJECTIVE: Skeletal involvement is a common clinical feature in acromegalic
      patients. Although several recent reports are available concerning bone mineral
      density (BMD) in acromegaly, the controversy still exists as to whether BMD of
      acromegalic patients is increased or not. The present study was performed to
      examine biochemical bone metabolic indices and BMD as well as body composition in
      26 Japanese patients with active acromegaly and 26 control subjects matched for
      age, sex, race and height in a cross-sectional study. MEASUREMENTS: BMD of the
      lumbar spine and femoral neck, as well as body composition, was measured by dual
      energy X-ray absorptiometry. Mid-radial BMD was measured by single-photon
      absorptiometry. We also determined serum levels of IGF-I, IGFBP-3 and osteocalcin
      (OC) as well as urinary levels of deoxy-pyridinoline (D-Pyr) and CrossLaps.
      RESULTS: Percent lean body mass was increased and percent fat mass was decreased
      in the acromegalic patients compared to control subjects. Serum levels of OC, as
      well as urinary levels of D-Pyr and CrossLaps, were significantly higher in
      acromegalic patients compared to control subjects (9.8 +/- 1.2 vs. 5.7 +/- 0.77
      for OC; 11.8 +/- 1.66 vs. 5.0 +/- 0.49 for D-Pyr; 437.6 +/- 68.4 vs. 156.5 +/-
      39.6 for CrossLaps). Z scores of BMD at mid-radius as well as lumbar spine and
      femoral neck were significantly higher in acromegalic patients compared to
      control subjects (1.086 +/- 0.311 vs. -0.060 +/- 0.274 for mid-radius; 1.022 +/-
      0.280 vs. 0.319 +/- 0.165 for lumbar spine; 1.292 +/- 0.347 vs. 0.232 +/- 0.264
      for femoral neck). CONCLUSIONS: The present study revealed that a decrease in
      percent fat mass and an increase in percent lean body mass were observed in
      Japanese patients with active acromegaly. Bone mineral density at all sites and
      bone metabolic markers were also increased in acromegaly. The present findings
      provide additional evidence that the GH/IGF-I axis might play an important role
      in the maintenance of bone mass as well as the regulation of body composition in
      Japanese adults.

PMID- 11531924
TI  - Efficacy of radiotherapy in normalizing serum IGF-I, acid-labile subunit (ALS)
      and IGFBP-3 levels in acromegaly.
AB  - OBJECTIVE: Radiotherapy (RT) has been used for many years in order to complete
      the cure of unsuccessfully operated acromegalic patients. Several studies have
      shown its efficacy in normalizing GH levels, while reports about IGF-I
      normalization are conflicting. Moreover, data regarding other markers of disease
      activity, such as IGFBP-3 and acid-labile subunit (ALS), i.e. the other two
      components of the circulating 150 kDa complex, are lacking. DESIGN: Retrospective
      study. PATIENTS AND MEASUREMENTS: Sixty-seven acromegalic patients (20 males and
      47 females, aged 40 +/- 6 years) who underwent postoperative RT (in fractionated
      doses for a total of 40-75 Gy) were followed-up for 11 +/- 6 years (range: 1-26
      years, median: 10 years). Serum GH and IGF-I levels off medical therapy were
      measured in all patients; ALS and IGFBP-3 were measured in 11 patients with
      normalization of IGF-I concentrations. Computed tomography or nuclear magnetic
      resonance imaging periodically assessed possible development of pituitary
      deficiency along with imaging of the hypothalamic-pituitary region. RESULTS:
      Forty-one out of 67 patients (58%) achieved GH levels < 2.5 microg/l by 1-15
      years after RT (mean 8 +/- 6) and 37/67 patients (55%) had normal or low IGF-I
      levels 1-26 years after RT (mean: 12 +/- 6), a normalization of both parameters
      being seen in 37 patients. GH < 2.5 microg/l and normal IGF-I levels were
      achieved in 17/26 (65%) patients followed-up for at least 15 years. ALS and IGFBP
      3 concentrations paralleled IGF-I levels in all patients studied. With respect to
      secondary pituitary insufficiency, acquired ACTH deficiency was found in 25
      patients, TSH deficiency in 20, gonadotropin deficiency in 23 and GH deficiency
      in seven. In total, two cases of meningioma and one pineal tumour, possibly
      related to RT, were seen 9-22 years after RT. CONCLUSIONS: RT is an effective,
      although slow-acting, therapeutic tool for acromegaly, with 'safe' GH levels and
      normal IGF-I concentrations being achieved in 65% of patients after 15 years. IGF
      I levels normalize more slowly than GH levels. Radiotherapy is able to normalize
      the concentration of all three components of the circulating 150 kDa complex.
      Checks for loss of pituitary function and appearance of second brain tumours must
      be carried out life-long.

PMID- 11531925
TI  - Tissue insulin sensitivity and body weight in polycystic ovary syndrome.
AB  - OBJECTIVE: Polycystic ovarian syndrome (PCOS) and obesity both affect insulin
      sensitivity. This study was designed to investigate the biochemical indices of
      PCOS and tissue insulin sensitivity in groups of lean and obese women with
      clinically equivalent degrees of the syndrome, relative to control subjects.
      DESIGN: A prospective study of in vivo parameters and in vitro study of
      adipocytes to assess insulin sensitivity. PATIENTS: Six lean and 14 overweight
      patients fulfilling formal diagnostic criteria for PCOS were studied. The degree
      of hirsutism and amenorrhoea was similar in each group. Eight control subjects
      were also studied. MEASUREMENTS: Endocrine and metabolic parameters were measured
      in lean and overweight patients with PCOS and control subjects. In vitro studies
      of adipocyte insulin receptor binding and adipocyte insulin action were
      performed. RESULTS: The mean plasma LH level was elevated in both groups of PCOS
      but was significantly higher in the lean group (LH levels were 25.1 +/- 3.1 and
      14.5 +/- 1.6 iu/l in lean PCOS and obese PCOS, respectively (P = 0.01)). There
      was a strong inverse correlation between BMI and LH levels (R = - 0.70, P =
      0.001). Fasting insulin levels were elevated in both lean and obese groups (11.5
      +/- 2.8 and 26.8 +/- 8.1 mU/l, respectively; P = 0.068). Mean serum testosterone
      and serum androstenedione levels were also elevated in PCOS compared to control
      subjects but there was no difference between the two groups of PCOS subjects.
      Insulin receptor binding in amenorrhoeic subjects with PCOS was low in both lean
      and obese patients with PCOS but was not significantly different between the two
      groups (0.79 +/- 0.17% and 0.66 +/- 0.07% per 10 cm2 cell membrane,
      respectively). Maximally insulin-stimulated rates of 3-O-methylglucose transport
      were low in both groups compared to previously studied normal subjects (0.96 +/-
      0.21 and 0.64 +/- 0.07 pmol per 10 cm2 membrane in lean and obese PCOS subjects,
      respectively; P = NS). CONCLUSIONS: Lean subjects with a given phenotypic
      expression of PCOS have an equivalent degree of tissue insulin resistance
      compared to obese PCOS subjects. This implies that the insulin resistance may be
      a primary feature of PCOS. If this is so, a similar clinical degree of the
      syndrome may be brought about by genetically determined insulin resistance in
      lean subjects or by insulin resistance which is secondary to obesity.

PMID- 11531926
TI  - Occurrence of ventricular late potentials in patients with active acromegaly.
AB  - OBJECTIVE: Patients with acromegaly have an increased risk of ventricular
      dysrhythmias and sudden death. Late potentials in a signal-averaged
      electrocardiogram (SAECG), a predictor of ventricular dysrhythmias, are
      frequently seen in patients after previous myocardial infarction, but little is
      known about the prevalence of late potentials in acromegaly. The aim of our study
      was to investigate the prevalence of late potentials in patients with acromegaly
      and their relation to the activity of the disease and to myocardial hypertrophy.
      PATIENTS: The study included 48 patients with acromegaly [27 males, 21 females,
      mean age 52.3 +/- 14.2 years, 16 active disease, 32 cured or 'well controlled',
      under treatment with sandostatin analogues (12/32)] and 38 healthy volunteers as
      a control group. RESULTS: Late potentials were detected in 9/16 (56%) patients
      with active acromegaly vs. 2/32 (6%) with cured/well controlled acromegaly (P =
      0.001), defined as normal age-related IGF-1 levels and GH levels suppressible
      below 1 microg/l after an oral glucose load (75 g). Late potentials were not
      related to muscle mass index (127 +/- 35 active vs. 123 +/- 34 g/m2 cured/well
      controlled). The association of disease activity with the detection of late
      potentials was independent of age, gender, duration of the disease and body mass
      index. In comparison to the control group, the prevalence of late potentials was
      significantly higher in patients with acromegaly (23%) than in the control group
      (0%; P < 0.001). CONCLUSIONS: Late potentials in the SAECG are frequently seen in
      active acromegaly and may represent an early and sensitive parameter to detect
      myocardial injury in acromegaly.

PMID- 11531927
TI  - Coronary risk in growth hormone deficient hypopituitary adults: increased
      predicted risk is due largely to lipid profile abnormalities.
AB  - BACKGROUND: Hypopituitarism in adults is associated with increased vascular
      mortality, which has been attributed to GH deficiency. OBJECTIVE: To compare the
      lipid profile and coronary risk predicted by the Framingham Heart Study equation
      in GH-deficient hypopituitary patients and healthy age and gender-matched
      controls. DESIGN: A cross-sectional observational study. METHODS: We studied 50
      adult-onset growth hormone deficient hypopituitary patients (23F, 27M), on
      appropriate conventional hormone replacement and 45 controls (22F, 23M) matched
      for age, gender and smoking habit. The subjects (age range 30-75 years) were free
      from diabetes, hypertension, ischaemic heart disease (IHD) and peripheral
      vascular disease. All hypogonadal male patients were on testosterone replacement
      therapy. A similar proportion of female patients (8/23) and controls (7/22) were
      on HRT. Body mass index (BMI), waist-hip ratio (WHR) and blood pressure were
      recorded. After an overnight fast blood glucose, total-cholesterol,
      triglycerides, HDL-cholesterol, apolipoproteins A-I, B and Lp (a) were measured.
      Coronary risk was calculated for each individual from age, gender, systolic blood
      pressure, total and HDL cholesterol, smoking habit and presence of diabetes and
      left ventricular hypertrophy using the Framingham equation. RESULTS: BMI and WHR
      were significantly increased in GHD hypopituitary adults of both sexes, but to a
      greater extent in females. Triglycerides were elevated in both sexes. Total and
      LDL-cholesterol were increased in both sexes (significantly only in males), and
      HDL cholesterol and apo A-I were lower (significantly only in females). The
      reduction in HDL cholesterol was correlated negatively with adiposity (BMI),
      particularly when centrally distributed (WHR) in patients and controls. LDL
      cholesterol did not correlate to adiposity but higher levels were present in GH
      deficient subjects. The total to HDL cholesterol ratio was significantly
      increased in patients of both genders (P = 0.002). There were no differences in
      the apolipoproteins B and Lp(a) between patients and controls. Absolute risk
      (mean +/- SEM) of a fatal or non-fatal coronary event during the next 5 years was
      significantly greater in GHD hypopituitary patients than control subjects (4.82
      +/- 0.73% vs. 2.94 +/- 0.53, P = 0.04). Cardiovascular risk relative to the local
      population (RR) was significantly higher in GHD hypopituitary adults (RR = 1.43
      CL 1.06-1.80, P = 0.011) but not in the control group (1.08 CL 0.59-1.6). When
      divided by gender, RR for male patients was not increased (1.14 CL 0.83-1.45, P =
      0.096). However, female patients had significantly higher RR (1.7 CL 1.05-2.5, P
      = 0.048). The RR for male and female controls was not different from the local
      population. CONCLUSION: Changes in lipid levels help to explain the results from
      risk factor modelling which show increased coronary risk in growth hormone
      deficient hypopituitary patients, particularly females. The abnormal lipid
      profile is characterized in both genders by an increase in the total to HDL ratio
      [corrected], an important parameter in the Framingham equation. The lipid
      abnormalities conferring increased risk is related to growth hormone deficiency
      either directly (LDL) or indirectly through increased central obesity (HDL)
      [corrected]. Adverse calculated coronary risk might provide a new objective
      indication for consideration of GH replacement therapy in adults.

PMID- 11531928
TI  - Urinary excretion of the aquaporin-2 water channel exaggerated in pathological
      states of impaired water excretion.
AB  - OBJECTIVE: The present study was undertaken to determine whether the hydro
      osmotic action of arginine vasopressin (AVP) is exaggerated in pathological
      states of impaired water excretion by measuring urinary excretion of the
      aquaporin-2 (AQP-2) water channel. PATIENTS AND MEASUREMENTS: Eighteen
      hyponatraemic patients with impaired water excretion and 12 control subjects were
      studied during an acute oral water load (20 ml/kg body weight). RESULTS: In the
      patient group plasma AVP levels were 1.6 pmol/l, relatively high compared to
      plasma osmolality of 279.8 mmol/kg. Urinary excretion of AQP-2 under ad libitum
      water drinking was 41.1 fmol/micromol creatinine in the patient group, a value
      significantly greater than that of 21.7 fmol/micromol creatinine in the control
      subjects. The acute water load verified the impairment in water excretion in the
      patient group, as the excretion of the water load was only 28.2% (control, 77.3%,
      P < 0.001) and the minimum urinary osmolality was as high as 437.3 mmol/kg
      (control, 122.9 mmol/kg, P < 0.001). Also, the minimum urinary excretion of AQP-2
      was significantly greater in the patient group than that in the control. There
      was a positive correlation between plasma AVP levels and urinary excretion of AQP
      2 in the control subjects (r = 0.56, P < 0.01). In contrast, the urinary
      excretion of AQP-2 was exaggerated compared to the respective plasma AVP levels
      in the patient group, and thus the positive correlation disappeared. CONCLUSION:
      These results indicate that hydroosmotic action of AVP is exaggerated more than
      that expected from plasma AVP levels in pathological states of impaired water
      excretion, with non-suppressible, but normal, arginine vasopressin levels in
      spite of the hypo-osmotic condition.

PMID- 11531929
TI  - Autoimmune thyroid syndrome in women with Turner's syndrome--the association with
      karyotype.
AB  - OBJECTIVE: Females with Turner's syndrome (TS) are at an increased risk of
      developing autoimmune thyroid disease. Studies assessing the influence of
      karyotype on thyroid autoimmunity in adults with TS have yielded conflicting
      results but have been limited by small numbers. The aim of this study was to
      determine the frequency of thyroid autoimmunity in a large cohort of women with
      TS and to assess the influence of karyotype on the development of thyroid
      disease. DESIGN, PATIENTS AND MEASUREMENTS: Data were available for 145 women
      with TS attending a dedicated adult Turner clinic. The mean age was 26 years
      (range 16-52 years). Information regarding the presence of thyroid disease,
      karyotype, thyroid autoantibodies and thyroid function was recorded in all. The
      chi-squared test with Yates' correction was used to assess the association
      between karyotype and thyroid autoimmunity. RESULTS: Forty-one per cent of women
      with TS had positive thyroid autoantibodies and 16% of women were hypothyroid on
      replacement therapy with thyroxine. However, 83% of women with an X-isochromosome
      had positive thyroid autoantibodies compared with 33% of women with other
      karyotypes (P < 0.0001). Women with an isochromosome-X karyotype were also
      significantly more likely to become frankly hypothyroid and require thyroxine
      compared with other karyotypes (37.5% isochromosome-X vs. 14% 45, X vs. 6% other
      karyotypes P = 0.0034). CONCLUSIONS: In this large cohort of women with TS we
      have shown that the risk of developing autoimmune thyroid disease is particularly
      high in women with an X-isochromosome, suggesting that a gene on the long arm of
      the X chromosome (Xq) may play an important pathogenetic role in the development
      of autoimmune thyroid disease.

PMID- 11531930
TI  - Hormone replacement therapy may improve hepatic function in women with Turner's
      syndrome.
AB  - OBJECTIVE: Women with Turner's syndrome (TS) have recently been shown to be at an
      increased risk of developing chronic liver disease. There has been some concern
      that oestrogen replacement therapy may exacerbate hepatic dysfunction. The aim of
      this study was to assess hepatic function in women with TS and to determine the
      effect of oral oestradiol valerate on liver enzymes. DESIGN AND PATIENTS: A
      retrospective review of liver enzymes of 80 women with TS, followed by a
      prospective study looking at serum liver enzyme concentrations in 20 women with
      TS following 3 months on and off hormone replacement therapy (HRT) (oestradiol
      valerate, 2 mg/levonorgestril 75 microg). MEASUREMENTS: Liver enzymes (gamma
      glutamyl transferase, aspartate transaminase and alkaline phosphatase), albumin
      and bilirubin were measured on and off HRT. Viral hepatitis serology and liver
      autoantibodies were tested in patients with abnormal liver function. RESULTS:
      Thirty-five out of 80 women (44%) had elevated serum liver enzyme concentrations.
      Two women (2.5%) had a mildly raised serum bilirubin, but protein synthesis was
      normal in all subjects. HRT resulted in a significant fall in all liver enzymes
      (P < 0.05) but did not affect serum protein concentrations CONCLUSIONS: Women
      with Turner's syndrome often have elevated liver enzymes. Oestrogen/progestagen
      therapy using oestradiol valerate improves liver function in this group of
      patients. The mechanisms behind this are unclear.

PMID- 11531932
TI  - Ras mutations are rare in solitary cold and toxic thyroid nodules.
AB  - OBJECTIVE: Activation of ras proto-oncogenes as a result of point mutations is
      detectable in a significant percentage of most types of tumour. Similar to
      neoplasms of other organs, mutations of all three ras genes can be found in
      thyroid tumours. H-, K- and N-ras mutations have been detected in up to 20% of
      follicular adenomas and adenomatous nodules which were not functionally
      characterized. This raises the question as to whether ras mutations are specific
      for hypofunctional nodules and TSH receptor mutations for hyperfunctioning
      nodules. DESIGN: To investigate ras and TSH receptor mutations with respect to
      functional differentiation we studied 41 scintigraphically cold nodules and 47
      toxic thyroid nodules. To address the likelihood of a somatic mutation we also
      studied the clonal origin of these tumours. MEASUREMENTS: Genomic DNA was
      extracted from nodular and surrounding tissue. Mutational hot spots in exons 1
      and 2 of the H- and K-ras gene were PCR amplified and sequenced using big dye
      terminator chemistry. Denaturing gradient gel electrophoresis (DGGE) was used to
      verify sequencing results for the H-ras gene and to analyse the N-ras gene
      because its greater sensitivity in detecting somatic mutations. Clonality of
      nodular thyroid tissue was evaluated using X-Chromosome inactivation based on PCR
      amplification of the human androgen receptor locus. RESULTS: Monoclonal origin
      was detectable in 14 of 23 informative samples from cold thyroid nodules. In
      toxic thyroid nodules the frequency of clonal tissue was 20 in 30 informative
      cases. Only one point mutation could be found in the N-ras gene codon 61 (Gly to
      Arg) in a cold adenomatous nodule which was monoclonal. In toxic thyroid nodules
      no ras mutation was detectable. CONCLUSION: Our study suggests that ras mutations
      are rare in solitary cold and toxic thyroid nodules and that the frequent
      monoclonal origin of these tumours implies somatic mutations in genes other than
      H-, K- and N-ras.

PMID- 11531931
TI  - Weight gain following treatment of hyperthyroidism.
AB  - OBJECTIVE: Patients frequently express concern that treating hyperthyroidism will
      lead to excessive weight gain. This study aimed to determine the extent of, and
      risk factors for, weight gain in an unselected group of hyperthyroid patients.
      DESIGN AND SUBJECTS: We investigated 162 consecutive hyperthyroid patients
      followed for at least 6 months. Height, weight, clinical features, biochemistry
      and management were recorded at each clinic visit. RESULTS: Documented weight
      gain was 5.42 +/- 0.46 kg (mean +/- SE) and increase in BMI was 8.49 +/- 0.71%,
      over a mean 24.2 +/- 1.6 months. Pre-existing obesity, Graves' disease causing
      hyperthyroidism, weight loss before presentation and length of follow-up each
      independently predicted weight gain. Patients treated with thionamides or
      radioiodine gained a similar amount of weight (thionamides, n = 87, 5.16 +/- 0.63
      kg vs. radioiodine, n = 62, 4.75 +/- 0.57 kg, P = 0.645), but patients who
      underwent thyroidectomy (n = 13) gained more weight (10.27 +/- 2.56 kg vs.
      others, P = 0.007). Development of hypothyroidism (even transiently) was
      associated with weight gain (never hypothyroid, n = 102, 4.57 +/- 0.52 kg,
      transiently hypothyroid, n = 29, 5.37 +/- 0.85 kg, on T4, n = 31, 8.06 +/- 1.42
      kg, P = 0.014). This difference remained after correcting for length of follow
      up. In the whole cohort, weight increased by 3.95 +/- 0.40 kg at 1 year (n = 144)
      to 9.91 +/- 1.62 kg after 4 years (n = 27) (P = 0.008), representing a mean
      weight gain of 3.66 +/- 0.44 kg/year. CONCLUSION: We have demonstrated marked
      weight gain after treatment of hyperthyroidism. Pre-existing obesity, a diagnosis
      of Graves' disease and prior weight loss independently predicted weight gain and
      weight continued to rise with time. Patients who became hypothyroid, despite T4
      replacement, gained most weight.

PMID- 11531933
TI  - Possible association but no linkage of the HSD11B2 gene encoding the kidney
      isozyme of 11beta-hydroxysteroid dehydrogenase to hypertension in Black people.
AB  - OBJECTIVE: The HSD11B2 (HSD11K) gene encoding the kidney isozyme of 11beta
      hydroxysteroid dehydrogenase is mutated in the syndrome of apparent
      mineralocorticoid excess, an autosomal recessive form of salt-sensitive
      hypertension. This gene is thus a logical candidate locus for risk of essential
      hypertension. DESIGN AND METHODS: Because hypertension in Black people tends to
      be of the low-renin, salt sensitive type, we genotyped independent sets of
      hypertensives of Afro-American (59 kindreds) and Afro-Caribbean (66 kindreds)
      origin using a highly polymorphic (heterozygosity index 0.84) CA repeat
      polymorphism in the first intron of HSD11B2. Linkage was assessed by the affected
      pedigree member method. RESULTS: No linkage of hypertension to this locus could
      be demonstrated, but statistically significant allelic associations were noted.
      CONCLUSIONS: HSD11B2 does not have a strong influence on the development of
      essential hypertension in Black people, but weaker effects on blood pressure
      cannot be ruled out.

PMID- 11531934
TI  - Additive effect of alfacalcidol on bone mineral density of the lumbar spine in
      Taiwanese postmenopausal women treated with hormone replacement therapy and
      calcium supplementation: a randomized 2-year study.
AB  - OBJECTIVE: To evaluate the effect of 1alpha-hydroxyvitamin D3 on bone mineral
      density of the lumbar spine in postmenopausal women receiving hormone replacement
      therapy and calcium supplement. DESIGN: A randomized, prospective 2-year clinical
      trial. PATIENTS AND MEASUREMENTS: A total of 240 postmenopausal women were
      enrolled with randomized assignment of 120 patients to each treatment group (the
      D + E group of 1alpha-hydroxyvitamin D3 + sequential combined HRT + calcium
      supplement; the E group: sequential combined HRT + calcium supplement). None of
      the patients had received HRT for menopausal syndrome or osteoporosis before
      being enrolled in our study. Serum biochemical assays, electrolytes and
      calcitonin were performed at baseline and after 6 and 12 months of treatment.
      Bone mineral density (BMD) of L2-L4 was measured by dual energy X-ray
      absorptiometry (DXA) at the initial assessment and after 12 and 24 months of
      treatment. RESULTS: One hundred and five patients (87.5%) in the D + E group and
      92 patients (76.7%) in the E group completed the first 1-year study. Ninety-six
      patients (80%) in the D + E group and 80 patients (66.7%) in the E group
      completed the 2-year trial. Renal function, liver function, electrolytes and
      calcitonin showed no significant changes during the first year of follow-up. In
      the D + E group, the BMD of L2-4 increased 3.24 +/- 0.32% from baseline after 1
      year (P < 0.05) and 5.32 +/- 0.23% after 2 years of treatment (P < 0.05). On the
      other hand, the changes of BMD in the E group were 1.12 +/- 0.34% after 1 year (P
      < 0.05) and 2.42 +/- 0.26% after 2 years of treatment (P < 0.05). The changes of
      BMD of L2-L4 of the D + E group were higher than the changes of the E group after
      both 1 and 2 years of treatment (P < 0.05). CONCLUSIONS: Our study demonstrated
      that combination of 1alpha-hydroxyvitamin D3 with HRT is superior to HRT alone
      for the preservation of bone mineral density in postmenopausal women under
      calcium supplementation.

PMID- 11531935
TI  - Elderly subjects show severe impairment of dehydroepiandrosterone sulphate and
      reduced sensitivity of cortisol and aldosterone response to the stimulatory
      effect of ACTH(1-24).
AB  - OBJECTIVE: Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis in
      ageing has been reported both in humans and in animals and may be involved in age
      related changes in body composition, structure functions and metabolism, as well
      as in brain ageing. Despite the supposed HPA hyperactivity and its refractoriness
      to negative glucocorticoid feedback, low levels of dehydroepiandrosterone (DHEA)
      and its sulphate have been clearly demonstrated in human ageing and may suggest
      another cause of age-related changes in structure function and metabolism. Thus,
      our aim was to verify the adrenal responsiveness to various ACTH doses in normal
      elderly subjects. DESIGN: We studied cortisol (F), aldosterone (A) and DHEA
      responses to the sequential administration of very low, low and supramaximal
      ACTH1-24 doses (0.06 microg or 0.5 microg followed by 250 microg ACTH1-24 i.v. at
      0 and +60 minutes) in healthy elderly subjects (ES) [six females and two males,
      aged 63-75 years, body mass index (BMI) 22-26 kg/m2]. The results in ES were
      compared with those recorded in healthy young subjects (YS) (six females and six
      males, aged 22-34 years, BMI 20-25 kg/m2). RESULTS: Basal DHEA levels in ES were
      lower (P < 0.05) than in YS, while F and A levels were similar in both groups.
      DHEA, F and A responses to ACTH were dose-dependent in both groups. In ES,
      however, DHEA levels showed no response to the 0.06 microg dose, a modest
      increase after 0.5 microg and a clearer rise after 250 microg ACTH; at any dose,
      the DHEA response in ES was clearly lower than in YS (P < 0.04). The F responses
      to 0.5 microg and 250 microg ACTH in ES were similar to those in YS; whereas, in
      ES, 0.06 microg ACTH elicited a non significant F increase which was
      significantly lower than in YS (P < 0.05). Similarly, the A responses to the
      highest ACTH doses were similar in both groups but, in ES, 0.06 microg ACTH
      elicited no increase in A secretion, which was clearly lower than in YS (P <
      0.03). CONCLUSIONS: Normal elderly subjects show severe reduction of DHEA
      response to a wide range of ACTH doses, in agreement with peculiar impairment of
      the activity of the adrenal reticularis zone in ageing. In contrast to young
      adults, elderly subjects also show no cortisol and aldosterone response to a very
      low ACTH dose. This evidence indicates a reduced sensitivity to ACTH in the
      fasciculata and glomerulosa zones of the adrenal gland in ageing.

PMID- 11531936
TI  - Extramedullary plasmacytoma in the adrenal incidentaloma.
AB  - High-resolution imaging has led to the increasingly frequent discovery of adrenal
      incidentalomas. Most are nonfunctioning tumours and adenomas, but it is difficult
      to distinguish benign from malignant tumours using only morphological and
      laboratory data, and the diagnosis often remains uncertain without histological
      examination. Here we report the case of a 52-year-old Japanese man who had a
      right adrenal incidentaloma 4 cm in diameter. The tumour was removed by
      laparoscopic adrenalectomy. The pathology specimen revealed the typical histology
      of plasmacytoma. Extramedullary plasmacytoma is a very rare type of plasma cell
      proliferative disorder. This is the first documented case of an extramedullary
      plasmacytoma in the adrenal gland.

PMID- 11531937
TI  - Dendritic cell immunotherapy in a neuroendocrine pancreas carcinoma.
AB  - OBJECTIVE: Metastatic neuroendocrine carcinomas of the pancreas frequently fail
      to respond to conventional therapies, including radiation and chemotherapy. We
      therefore tested a dendritic cell-based immunotherapy in an attempt to eradicate
      residual tumour masses in a patient suffering from a metastatic insulin-producing
      pancreatic carcinoma. DESIGN: Autologous dendritic cells (DCs) were generated
      from peripheral blood monocytes in the presence of granulocyte/macrophage colony
      stimulating factor, interleukin-4 and tumour necrosis factor alpha. DCs were
      loaded with tumour-derived lysate (TL), and were delivered by subcutaneous
      injections in 4-week intervals. RESULTS: Three weeks after first treatment, the
      patient developed a strong delayed-type hypersensitivity (DTH) skin reaction with
      an erythema and induration after the challenge with TL-pulsed DCs, which
      indicates the efficient generation of antigen-specific memory T-cells.
      Immunohistochemical analysis of skin biopsy demonstrated a strong perivascular
      and epidermal infiltration by T-helper (CD4 positive) and cytotoxic T cells (CD8
      positive). Stimulation with TL revealed a dose-dependent T-cell proliferation
      with a stimulation index of 1.1-5.7 compared to 1.1-1.4 before vaccination (P <
      0.01). Most strikingly, DC-based vaccination was accompanied by a steady decrease
      of the tumour marker chromogranin A from 2.93 umol/l initially to below the
      detection limit of 0.15 umol/l within 9 months of therapy. The ultrasound
      examination revealed a tumour regression of the metastasis in the right lobe of
      the liver. CONCLUSIONS: Our data indicate that vaccination with tumour lysate
      pulsed DCs induced a significant antitumour immune response in a neuroendocrine
      carcinoma of the pancreas. This approach represents an alternative strategy for
      the treatment of advanced neuroendocrine carcinomas that are resistant to
      conventional therapy.

PMID- 11531938
TI  - Impaired vascular reactivity in primary hyperparathyroidism may contribute to
      cardiovascular risk.

PMID- 11531939
TI  - Antihypertensive drug urapidil metabolites interfere with metanephrines assays.

PMID- 11531940
TI  - Yes T cells, but three different T cells (alphabeta, gammadelta and NK T cells),
      and also B-1 cells mediate contact sensitivity.
AB  - Transfer of contact sensitivity (CS) responses by immune lymphoid cells was the
      first finding that distinguished cellular from humoral immunity. CS has remained
      the most studied T cell reaction in vivo, and is the prototype for a variety of
      delayed-type hypersensitivity (DTH) responses. DTH in essence is the recruitment
      of effector alphabeta-T cells out of vessels into peripheral tissues. The T cells
      then are activated by antigen presenting cells to produce pro-inflammatory
      cytokines. It has been assumed that the alphabeta-T cells alone are responsible,
      but recent studies show that three other lymphocyte subsets are involved: CS
      inducing NK T cells, CS-initiating B-1 cells, and CS-assisting gammadelta-T
      cells. Therefore, the effector alphabeta-T cells are essential, but cannot be
      recruited into the tissues without the local action of IgM antibodies produced by
      B-1 cells rapidly (1 day) post-immunization. The IgM complexes with the challenge
      antigen to locally activate complement to lead to vascular activation required
      for T cell recruitment. This process occurs early (1-2 hours) in the elicitation
      phase, and is called CS-initiation. The essential CS-inducing NK T cells activate
      the B-1 cells by producing IL-4 rapidly (1 hour) after immunization, and
      gammadelta-T cells assist the local inflammatory function of the recruited CS
      effector alphabeta-T cells. Thus, four lymphocyte subsets are required for
      elicitation of responses: CS-inducing NK T cells, CS-initiating B-1 cells, CS
      assisting gammadelta-T cells, and finally the CS-effector alphabeta-T cells.
      Three of these four cell types are present in the immune lymphoid cell population
      that adoptively transfers CS: B-1 cells, gammadelta-T cells, and the alphabeta-T
      cells.

PMID- 11531941
TI  - Gammadelta T cells assist alphabeta T cells in the adoptive transfer of contact
      hypersensitivity to para-phenylenediamine.
AB  - Para-phenylenediamine (PPD) is known to be a common sensitizer of allergic
      contact dermatitis and contact urticaria. To clarify the mechanism of contact
      hypersensitivity (CHS) to PPD, we established a mouse model of PPD-induced CHS.
      BALB/c mice were immunized for 3 consecutive days by painting topically a 2.5%
      PPD solution on their shaved abdominal skin. On days 5, 7 or 9 after the initial
      application, the mice were challenged by applications of a 2.5% PPD solution.
      Maximal ear swelling was determined at 24 h but another statistically significant
      and smaller ear swelling was observed 1 h after challenge with PPD in a hapten
      specific manner. Adoptive cell transfer experiments demonstrated that the ear
      swelling of the adoptive cell transferred mice displayed an early response at 6 h
      and a late response from 12 h to 24 h when the recipient mice were challenged
      immediately after transfer. Both MoAbs and complement treatment of the
      transferred cells demonstrated that the phenotype of the early response cells
      which elicited a response at 6 h after challenge was Thy1(+), B220(+), alphabeta
      TCR(-), gammadelta TCR(-), CD3(-), CD4(-), CD5(+) and CD8(-). The in vitro
      treatment of effector cells with MoAbs against not only alphabeta TCR but also
      gammadelta TCR, together with complement, was found to diminish substantially the
      late response, elicited 12-24 h after challenge. Gammadelta T cells reconstituted
      the ability of alphabeta T cells to transfer 24 h CHS responsiveness. The
      phenotype of the gammadelta T cells that assist CHS effector alphabeta T cells
      was CD3(+), CD4(-) and CD8(+) and these regulatory gammadelta T cells were
      neither Ag-specific nor MHC-restricted. Furthermore, gammadelta T cells from
      normal spleen could also assist alphabeta T cells in adoptive transfer of the 24
      h CHS response in a non-MHC-restricted manner. RT-PCR demonstrated that alphabeta
      T cells strongly expressed mRNA IFN-gamma, whereas gammadelta T cells expressed
      not only IFN-gamma but also IL-4 and IL-10. These data indicate that not only
      early response cells and alphabeta T cells but also Th2 type gammadelta T cells
      may play an important role in the elicitation of CHS to PPD.

PMID- 11531942
TI  - C1q-bearing immune complexes induce IL-8 secretion in human umbilical vein
      endothelial cells (HUVEC) through protein tyrosine kinase- and mitogen-activated
      protein kinase-dependent mechanisms: evidence that the 126 kD phagocytic C1q
      receptor mediates immune complex activation of HUVEC.
AB  - Endothelial cells play a pivotal role in the initiation and perpetuation of
      inflammation. C1q, the first component of the classical pathway of complement, is
      a potent stimulus leading to endothelial cell activation and cytokine production.
      The specific cellular mechanisms through which endothelial cells are stimulated
      by C1q are not known. We stimulated human umbilical vein endothelial cells
      (HUVEC) with either monomeric C1q or C1q-bearing immune complexes (C1q-IC) in the
      presence or absence of inhibitors of protein tyrosine kinases (PTK) or mitogen
      activated protein kinases (MAPK). C1q-IC, but not monomeric C1q, induced IL-8
      production in dose- and time-dependent fashion. R3, a cross-linking monoclonal
      IgM antibody against the 126 kD phagocytic C1q receptor (C1qR), also stimulated
      IL-8 production. IL-8 mRNA accumulation was detected by Northern blot analysis
      within 2 h of stimulation by the immune complexes and was enhanced by the
      addition of cycloheximide. Secretion of IL-8 by C1q-IC stimulated HUVEC was
      completely blocked by the PTK inhibitor, genistein or the MAPK inhibitor, UO126.
      These experiments demonstrate that C1q-IC-induced production of IL-8 in HUVEC is
      dependent upon the activation of PTK and MAPK. These findings also support a role
      for the phagocytic C1qR as an important activator of HUVEC by immune complexes.

PMID- 11531943
TI  - The polymorphic IL-1B and IL-1RN genes in the aetiopathogenesis of peptic ulcer.
AB  - Besides environmental factors, the genetic background of an individual may
      contribute to the development and final outcome of peptic ulcer disease.
      Interleukin-1beta (IL-1beta) and the interleukin-1 receptor antagonist (IL-1ra)
      are cytokines that play a key role in modulating the inflammatory response in the
      gastrointestinal mucosa. This study aimed to investigate whether polymorphisms in
      the IL-1B and IL-RN genes are involved in the susceptibility to and final outcome
      of peptic ulcer disease. DNA from 179 unrelated Spanish Caucasian patients with
      peptic ulcer diseases and 99 ethnically matched healthy controls was typed for
      the TaqI polymorphism at position + 3954 in the IL-1B gene and the variable
      number of tandem repeats polymorphism in intron 2 of the IL-1RN gene. The
      determination of Helicobacter pylori status and non-steroidal anti-inflammatory
      drug (NSAIDs) use was studied in all patients and in controls. H. pylori
      infection and NSAID use were more frequent in ulcer patients than in controls.
      There were no significant differences in carriage rate, genotype and allele
      frequencies of the IL-1RN and the IL-1B(+3954) gene polymorphisms between peptic
      ulcer patients and controls. However, a strong allelic association between IL-1B
      and IL-1RN genes was found in duodenal ulcer patients (P < 0.0006). Logistic
      regression identified H. pylori infection and NSAIDs use as independent risk
      factors for peptic ulcer diseases whereas the simultaneous carriage of IL
      1B(+3954) allele 2 and IL-1RN allele 2 was associated with reduced risk for
      duodenal ulcer disease (OR: 0.37, 95% CI = 0.14-0.9). Our data suggest that IL-1B
      and IL-1RN genes in addition to bacterial and environmental factors play a key
      role in determining the final outcome of peptic ulcer disease.

PMID- 11531944
TI  - Flow cytometric measurement of intracellular migration inhibition factor and
      tumour necrosis factor alpha in the mucosa of patients with coeliac disease.
AB  - There is increasing evidence that proinflammatory cytokines contribute to many of
      the small intestinal features in coeliac disease. The aim of the study was to
      investigate the expression of two proinflammatory cytokines, migration inhibition
      factor (MIF) and tumour necrosis factor alpha (TNF-alpha) in duodenal biopsy
      specimens from patients with coeliac disease on a gluten-free diet and normal
      control subjects. A flow cytometric system was used to analyse intracellular
      protein levels of MIF and TNF-alpha in freshly isolated cells from duodenal
      biopsies taken from 12 patients with treated coeliac disease and 10 healthy
      control subjects. From the biopsy specimens, single cell suspensions of the
      epithelium and lamina propria were prepared using EDTA/DTT and enzymes.
      Intracellular cytokine expression was studied in intraepithelial lymphocytes
      (IELs), lamina propria T cells (LP T) and intestinal epithelial cells using
      different surface labelling antibodies. MIF protein was constitutively expressed
      in IELs, LP T cells and epithelial cells from normal intestinal mucosa. In
      contrast, although TNF-alpha was found in LP T cells, this cytokine was virtually
      undetectable in either IELs or epithelial cells. In coeliac disease,
      intracellular levels of MIF were significantly higher in epithelial cells
      compared with control subjects (P = 0.005). Raised levels of TNF-alpha were found
      in epithelial cells (P = 0.03) as well as IELs (P = 0.045) from coeliac patients
      compared with controls. The findings from this study show up-regulated expression
      of MIF and TNF-alpha in IELs and epithelial cells of histologically normal mucosa
      in patients with coeliac disease. Increased expression of proinflammatory
      cytokines in cells occupying the epithelial layer could help explain the rapidity
      with which the coeliac mucosa may respond to gluten challenge.

PMID- 11531945
TI  - The proportion of Th1 cells, which prevail in gut mucosa, is decreased in
      inflammatory bowel syndrome.
AB  - T lymphocytes and their cytokines have an important role in the regulation of
      immune responses in the gut and in the pathogenesis of intestinal inflammation
      such as in Crohn's disease. The aim of this study was to analyse the Th1/Th2
      cytokine profile (IFN-gamma, IL-2, IL-4 and IL-10) in intraepithelial lymphocytes
      (IEL) and lamina propria lymphocytes (LPL) in Crohn's disease (CD) and ulcerative
      colitis (UC) in relation to healthy controls (C). Colonic and ileal biopsy
      specimens were obtained from controls (n = 13) and patients with CD (n = 32).
      Colonic biopsies were obtained from patients with UC (n = 11). Intracytoplasmic
      IFN-gamma, IL-2, IL-4 and IL-10 were determined by flow cytometry after PMA
      ionomycin stimulation in IEL and LPL. In colonic LPL, a significant proportional
      decrease of IFN-gamma and IL-2 producing CD3+ cells was observed in patients with
      CD and UC compared to controls. In ileal LPL, a similar tendency was found
      although differences were not significant. In IEL no differences in cytokine
      profiles could be observed. Flow cytometric analysis of intracytoplasmic
      cytokines at single cell level showed a proportional decrease of IFN-gamma and IL
      2 producing T cells in colonic lamina propria in patients with inflammatory bowel
      disease.

PMID- 11531946
TI  - Identification of ricin A-chain HLA class II-restricted epitopes by human T-cell
      clones.
AB  - The identification of ricin toxin A-chain (RTA) epitopes and the molecular
      context in which they are recognized will allow strategies to be devised that
      prevent/suppress an anti-RTA immune response in patients treated with RTA-based
      immunotoxins. RTA-specific human T-cell lines and T-cell clones were produced by
      in vitro priming of PBMC. The T-cell clones used a limited set of Vbeta chains
      (Vbeta1, Vbeta2 and Vbeta8) to recognize RTA epitopes. The use of RTA deletion
      mutants demonstrated that T-cell lines and T-cell clones from three out of four
      donors responded to RTA epitopes within the domain D124-Q223, whereas one donor
      recognized the region I1-D124. The response to RTA peptides of T-cell lines and T
      cell clones from two donors allowed the identification of immunogenic segments
      (D124-G140 and L161-T190) recognized in the context of different HLA-DRB1 alleles
      (HLA-DRB1*0801, and HLA-DRB1*11011 and B1*03011, respectively). The response to
      L161-T190 was investigated in greater detail. We found that the HLA-DRB1*03011
      allele presents a minimal epitope represented by the sequence I175-Y183 of RTA,
      whereas the HLA-DRB1*11011 allele presents the minimal epitope M174-I184. RTA
      peptides and an I175A RTA point mutant allowed us to identify I175 as a crucial
      residue for the epitope(s) recognized by the two HLA-DRB1 alleles. Failure of T
      cell clones to recognize ribosome inactivating proteins (RIPs) showing sequences
      similar but not identical to RTA further confirmed the role of I175 as a key
      residue for the epitope recognized in the context of HLA-DRB1*11011/03011
      alleles.

PMID- 11531947
TI  - Interferon-gamma administration after abdominal surgery rescues antigen-specific
      helper T cell immune reactivity.
AB  - Antigen-induced activation of T cells is determined by many factors. Among these
      factors are (i) the number of T-cell receptors (TCRs) triggered by TCR ligands on
      antigen-presenting cells (APCs), and (ii) the intrinsic cellular threshold for
      activation. T-cell receptor triggering is optimized by adhesion molecules that
      form the interaction site between T cells and APCs, i.e. the immunological
      synapse. In addition, signals through co-stimulatory molecules lower the
      intrinsic T-cell activation threshold. Immunosuppressive agents and traumatic
      events such as major operative procedures change physiological T-cell responses.
      Depressed immune functions after surgery are presumed to render patients more
      susceptible to pathogens. Interferon-gamma (IFNgamma) is a type II homodimeric
      cytokine with multiple immunostimulatory properties. Several studies have been
      performed to assess the effects of IFNgamma treatment in patients in need of
      increased immune reactivity. However, until now, the effect of IFNgamma on human
      antigen specific CD4(pos) T-cell reactivity after surgically-induced
      immunosuppression has not been reported. Therefore, a comparative trial of
      recombinant human (rh) IFNgamma versus placebo in patients after abdominal
      surgery was initiated. Antigen-specific helper T cell immune reactivity was
      assessed by antigen-induced cytokine production, intracellular cytokine staining
      and flow cytometry. A single dose of rhIFNgamma rescued down-modulation of
      antigen-specific CD4(pos) T-cell reactivity, concomitant with an up-regulation of
      TCR-ligands on antigen-presenting cells. Selected patients may benefit from the
      immunostimulatory properties of rhIFNgamma administration in vivo.

PMID- 11531948
TI  - Both age and gender affect thymic output: more recent thymic migrants in females
      than males as they age.
AB  - The thymus undergoes age-associated involution, with studies showing thymic size
      decreasing from birth at a rate of approximately 3% per year until middle age,
      and at a rate of 1% per year thereafter. The aim of this study was to determine
      the effect of thymic atrophy on T-lymphocyte production by the thymus, and to
      clarify the ongoing uncertainty regarding gender differences in thymic function.
      We quantified recent thymic emigrants (RTEs) in blood through the measurement of
      signal joint T-cell receptor rearrangement excision circles (sjTRECs), and showed
      that the decline in the number of RTEs in the blood with increasing age is gender
      linked. Peripheral blood from females contained significantly higher levels of
      sjTRECs per CD3+ T cell than blood from males (P = 0.002), despite there being no
      significant gender difference in the absolute number of CD3+ T cells in the
      populations analysed (P > 0.10). Our findings suggest better thymic function in
      females compared with males, providing females with a higher number of recent
      thymic emigrants for longer periods of life. Such a finding provides a plausible
      explanation for the immunological gender differences observed in previous studies
      and possibly, for the general longer life expectancy in females compared with
      males.

PMID- 11531949
TI  - Down-regulation of CXCR1 and CXCR2 expression on human neutrophils upon
      activation of whole blood by S. aureus is mediated by TNF-alpha.
AB  - It was suggested that bacterial products can inhibit the expression of leucocyte
      chemokine receptors during sepsis and affect leucocyte functions in septic
      syndrome. Superantigens and toxins produced by Staphylococcus aureus are capable
      of activating leucocytes via binding to MHC-II antigens on monocytes and T-cell
      receptor molecules on T lymphocytes. It was recently shown that staphylococcal
      enterotoxins directly down-regulate the expression of CC chemokine receptors on
      monocytes through binding to MHC class II molecules. We studied the effects of
      killed S. aureus on the expression of interleukin-8 receptors, CXCR1 and CXCR2,
      on polymorphonuclear leucocytes (PMN), which are known to lack the expression of
      MHC-II antigens. It was shown that S. aureus down-regulated the cell-surface
      expression of CXCR1 and CXCR2 on PMN in the whole blood and total blood leucocyte
      fraction containing PMN and monocytes, but did not modulate IL-8 receptor
      expression in purified PMN suspension. Antibody to TNF-alpha abrogated down
      regulation of IL-8 receptors induced by S. aureus. In contrast, LPS reduced CXCR1
      and CXCR2 expression in purified PMN and whole blood in a TNF-alpha-independent
      manner. We further showed that TNF-alpha-induced decrease of CXCR1 and CXCR2
      expression was associated with lower IL-8 binding and lower CXCR1 and CXCR2 mRNA
      levels, and was abrogated by protease inhibitors. We suggest that during
      septicemia, S. aureus may inhibit neutrophil responsiveness to IL-8 and other CXC
      chemokines via TNF-alpha- mediated down-regulation of CXCR1 and CXCR2.

PMID- 11531950
TI  - Antigen processing for MHC class I restricted presentation of exogenous influenza
      A virus nucleoprotein by B-lymphoblastoid cells.
AB  - In general, exogenous proteins are processed by antigen-presenting cells in the
      endosomes for major histocompatibility complex (MHC) class II presentation to
      CD4+ T cells, while proteins synthesized endogenously are processed in the
      cytoplasm for MHC class I presentation to CD8+ T cells. However, it is recognized
      that exogenous proteins can be processed for MHC class I presentation also, and
      evidence in favour of alternatives to the conventional MHC class I processing and
      presentation pathway is accumulating. Here, we show that exogenous recombinant
      influenza A virus nucleoprotein (rNP) is processed for MHC class I presentation
      to CD8+ cytotoxic T lymphocytes (CTL) by EBV-transformed, B-lymphoblastoid cell
      lines (B-LCL). Processing of rNP for HLA-B27-associated presentation seemed to
      follow the conventional MHC class I pathway predominantly, as presentation was
      diminished in the presence of lactacystin and brefeldin A, but was less sensitive
      to chloroquine and NH4Cl. HLA-B27-associated presentation was also observed using
      cells lacking a functional transporter associated with antigen processing,
      suggesting that alternative pathways may be exploited for processing of rNP.

PMID- 11531951
TI  - Ex vivo analysis of phenotype and TCR usage in relation to CD45 isoform
      expression on cytomegalovirus-specific CD8+ T lymphocytes.
AB  - Human cytomegalovirus (CMV) is a ubiquitous pathogen which sets up a lifelong
      persistent infection and which can lead to significant disease in the
      immunosuppressed. The immunological mechanisms controlling CMV in the long term
      are not defined completely, but CD8+ T lymphocytes are thought to play an
      important role. Antiviral CD8+ T lymphocytes may exist in very large pools in
      healthy individuals. Although the detailed composition of these pools is not
      completely understood, there is known to be heterogeneity, in particular of CD45
      isoform expression. We have therefore investigated the CD8+ T-lymphocyte response
      against CMV directly ex vivo using Class I tetramers combined with stains for a
      range of phenotypic markers followed by four-colour flow cytometric analysis. In
      particular, we examined expression of these phenotypic markers in relation to the
      expression of CD45 isoforms. We found that a spectrum of phenotypes exists
      stably, from CD45R0(high)/RA(low) through CD45RA(high)/R0(low), and that
      expression of other surface markers such as CD28 and CD62L, and also TCR usage,
      may vary in parallel with CD45 isoform expression. In some individuals,
      expansions of antigen-specific CD8+ T lymphocytes bearing specific TCR Vbeta
      chains were restricted to cells of particular CD45 isoforms. Immunity against CMV
      comprises a large population of CD8+ T lymphocytes with heterogeneous potential,
      a spectrum in which CD45 isoform expression may play a central role.

PMID- 11531952
TI  - Changes in thymic function in HIV-positive patients treated with highly active
      antiretroviral therapy and interleukin-2.
AB  - Despite its potent antiviral activity, highly active antiretroviral therapy
      (HAART) only exerts a marginal effect on CD4+ T-cell regeneration in HIV-infected
      subjects. Combination therapies aimed at boosting T-cell activity and maturation
      may provide an important contribution to the restoration of immune function.
      Here, we report the results obtained by a two-year follow-up of a cohort of HIV
      infected patients treated with a combination of HAART and interleukin-2 (IL-2).
      In these patients, in addition to a series of quantitative virological and
      immunological parameters, we investigated T-cell regeneration by an
      immunophenotypic assay monitoring CD4+ naive T cells, and by analysis of thymic
      function, through the quantification of the excision DNA products of T-cell
      receptor rearrangement (TRECs) in lymphocytes. Compared with HAART alone, we
      found that the IL-2 combination therapy was equally effective in reducing the
      levels of viremia and marginally more effective in decreasing proviral DNA load.
      Strikingly, the IL-2 combination produced a marked increase in the number of CD4+
      T cells bearing a naive phenotype (CD45RA+, CD62L+), which was apparent for over
      96 weeks after therapy. To assess whether these cells were the product of
      improved T-cell generation, we exploited a competitive quantitative molecular
      assay to quantify TRECs in peripheral blood lymphocytes. Surprisingly, we found
      that the levels of these molecules were unchanged in these patients. These
      findings indicate that improved thymic function does not account for the early
      rise of CD4 naive cells in HIV-positive patients treated with IL-2, and suggest
      that alternative mechanisms of T-cell maturation and differentiation are
      responsible for this event.

PMID- 11531953
TI  - T-cell re-population in HIV-infected children on highly active anti-retroviral
      therapy (HAART).
AB  - In this pilot study, we address the nature of the re-population of the T-cell
      compartment in HIV-1+ (Human Immunodeficiency Virus 1), vertically infected
      children placed on successful regimens of HAART (highly active anti-retroviral
      therapy) incorporating 2 NRTI and a protease inhibitor. The clonality of the T
      cell compartment and the abundance of RTEs (Recent Thymic Emigrants) were
      determined 2 weeks before and 20 weeks after initiation of HAART in a subgroup of
      children taking part in the PENTA (Paediatric European Network for the Treatment
      of AIDS) 5 trial. Analysis of the clonality of the circulating T-cell compartment
      was assessed using CDR3 spectratyping and analysed using the Kolmogorov-Smirnov
      two sample test. This revealed that a high degree of T-cell clonal restriction
      still exists 5 months into therapy, despite the appearance of previously
      undetectable T-cell clones within the periphery. We detected no increase in RTE
      abundance in this 5 month period, as determined by PCR detection of TRECs (T-Cell
      Receptor Excision Circles). We conclude that the observed re-population of T
      cells within the periphery of treated children is heavily reliant upon the
      maintenance/expansion of pre-existing cells during the 5 month period immediately
      following the initiation of therapy.

PMID- 11531954
TI  - Placental cytokine and chemokine production in HIV-1-infected women: trophoblast
      cells show a different pattern compared to cells from HIV-negative women.
AB  - In utero transmission of HIV-1 has been demonstrated and may account for around
      10-20% of all materno-fetal HIV-1 transmission. The possible routes for such
      transmission are transannexial or transplacental. In both cases, the
      microenvironment (cytokines and chemokines) at the placental interface could be
      an important regulatory factor in viral transmission. We therefore performed
      explant cultures of placental villi, and isolated purified trophoblasts, from
      term placentae obtained from HIV-1-seropositive and HIV-1-seronegative women in
      order to assess and compare the cytokine and chemokine secretion profiles using
      ELISA and semiquantitative RT-PCR. No major differences could be seen in the
      secretions of cytokines and chemokines at the level of whole placental tissue in
      HIV-1-positive and HIV-1-negative women. However, variations were observed in the
      expression of inflammatory cytokines and chemokines from trophoblastic cells,
      depending on the status of HIV-1 infection of the mothers but not the babies, all
      of which remained uninfected. The significance of these data is discussed.

PMID- 11531955
TI  - Influence of the IL-1Ra gene polymorphism on in vivo synthesis of IL-1Ra and IL
      1beta after live yellow fever vaccination.
AB  - The inflammatory response in infectious and autoimmune diseases is regulated by
      the balance between pro- and anti-inflammatory cytokines. The IL-1 complex
      contains polymorphic genes coding for IL-1alpha, IL-1beta and IL-1Ra. The IL-1Ra
      (variable number of tanden repeat) VNTR polymorphism has been shown to influence
      the capacity to produce IL-1beta and IL-1Ra after in vitro stimulation. Allele 2
      of this polymorphism is associated with a number of inflammatory diseases. To
      determine the impact of the IL-1Ra polymorphism on in vivo human cytokine
      synthesis, we used a yellow fever vaccination model for the induction of cytokine
      synthesis in healthy volunteers. Two different yellow fever vaccines were used.
      After administration of the RKI vaccine (34 volunteers), plasma TNF-alpha
      concentration increased from 13.4 +/- 0.9 pg/ml to 23.3 +/- 1.1 pg/ml (P <
      0.001), and plasma IL-1Ra concentration increased from 308 +/- 25 pg/ml to 1019
      +/- 111 pg/ml (P < 0.001), on day 2. Using Stamaril vaccine, no increase in the
      plasma concentrations of either TNF-alpha or IL-1Ra could be detected (n = 17).
      Only the RKI vaccine induced TNF-alpha synthesis after in vitro stimulation of
      MNC. Carriers of allele 2 of the IL-1Ra polymorphism had increased baseline
      concentrations of IL-1Ra (350 +/- 32 pg/ml) compared with non-carriers (222 +/-
      18 pg/ml, P < 0.001), and decreased concentrations of IL-1beta (0.9 +/- 0.2 pg/ml
      for carriers versus 2.8 +/- 0.7 pg/ml for non-carriers, P = 0.017). After yellow
      fever vaccination (RKI vaccine), no significant differences in the increase of IL
      1Ra plasma levels were detected between carriers and non-carriers of allele 2 of
      the IL-1Ra gene polymorphism. This is the first study to examine the influence of
      this genetic polymorphism on in vivo-induced human IL-1beta and IL-1Ra synthesis.
      Baseline concentrations of IL-1Ra and IL-1beta were significantly influenced by
      the IL-1Ra polymorphism. No influence of the IL-1Ra polymorphism on the in vivo
      induced production of IL-1Ra and IL-1beta could be detected.

PMID- 11531956
TI  - Prevention of adjuvant arthritis by the W3/25 anti-CD4 monoclonal antibody is
      associated with a decrease of blood CD4(+)CD45RC(high) T cells.
AB  - Imbalance between Th1 and Th2 functions is considered to play a key role in the
      induction and development of several autoimmune diseases, and the correction of
      that imbalance has led to effective therapies of some experimental pathologies.
      To examine whether CD4(+)CD45RC(high) (Th1-like) and CD4(+)CD45RC(low) (Th2-like)
      lymphocytes play a role in the pathogenesis of adjuvant arthritis (AA) and in its
      prevention by anti-CD4 antibody, CD45RC expression on CD4(+) T cells was
      determined in arthritic rats and in animals treated with an anti-CD4 MoAb (W3/25)
      during the latency period of AA. The phenotype of regional lymph node lymphocytes
      from arthritic rats in the active phase of the disease was determined by flow
      cytometry. Peripheral blood lymphocytes from rats treated with W3/25 MoAb were
      also analysed for 2 weeks after immunotherapy finished. IgG2a and IgG1 isotypes
      of sera antibodies against the AA-inducing mycobacteria, considered to be
      associated with Th1 and Th2 responses, respectively, were also determined by
      ELISA techniques. Fourteen days after arthritis induction, regional lymph nodes
      presented an increase in CD4+CD45RC(high) T cell proportion. Preventive
      immunotherapy with W3/25 MoAb inhibited the external signs of arthritis and
      produced a specific decrease in blood CD4(+)CD45RC(high) T cells and a diminution
      of antibodies against mycobacteria, more marked for IgG2a than for IgG1 isotype.
      These results indicate a possible role of CD4(+)CD45RC(high) T lymphocytes in the
      pathogenesis of AA, and suggest that the success of anti-CD4 treatment is due to
      a specific effect on CD4(+)CD45RC(high) T subset that could be associated with a
      decrease in Th1 activity.

PMID- 11531957
TI  - Antigen presentation of Type II collagen in rats.
AB  - Collagen-induced arthritis (CIA) is a T-cell dependent disease of rats which
      follows immunization with bovine type II collagen (bCII). Susceptibility to CIA
      is linked to the genes encoding the major histocompatibility complex (MHC),
      suggesting that antigen presentation is important in disease pathogenesis.
      Antigen-presenting cells (APC) (macrophages, dendritic cells (DC) and B cells)
      were prepared from WA/KIR/KCL rats and presentation of antigen, in the form of
      native protein (bCII) or synthetic peptide (bCII:184-198), was assessed in T-cell
      proliferation assays. Whilst macrophages inhibited proliferative responses to
      bCII, splenic or thymic low density cells, enriched for DC, presented both bCII
      and bCII(184-198) peptide. However, bone marrow-derived DC, which stimulated T
      cell responses to OVA, failed to present bCII, suggesting differences in
      processing of these two antigens. B-cell depletion from lymph node cells
      abrogated the proliferative response to bCII and reconstitution of a T-cell
      population with B cells restored the proliferative response, indicating that B
      cells are important for stimulating T-cell responses to bCII. B cells play a
      critical role in CIA by producing pathogenic anti-bCII antibodies, and we propose
      that B cells are also important APC which present bCII to CD4+ T cells.

PMID- 11531958
TI  - HLA-DR expression on lymphocyte subsets as a marker of disease activity in
      patients with systemic lupus erythematosus.
AB  - A major problem in the management of SLE patients is to predict a flare or to
      distinguish between active and quiescent disease. Serological markers are widely
      used to assess disease activity, but many patients have close to or normal values
      for these parameters while exhibiting obvious disease-related signs and symptoms.
      This study aimed to determine which serological parameters, among ESR, ANA and
      anti-dsDNA antibody titres, CH50 and the HLA-DR expression on circulating T
      lymphocyte subsets, best reflected the development of SLE flares. Sixty SLE
      patients were included, 34 with quiescent disease throughout the entire follow-up
      period and 26 who experienced an SLE flare defined as having active disease.
      According to univariate analysis, all parameters were significantly higher for
      patients with active disease, with the percentage of CD8+DR+ cells being the most
      significant parameter (P = 10-7). Multivariate logistic regression analysis
      identified three independent variables enabling the identification of a lupus
      flare: CH50, the CD8+DR+ and CD4+DR+ cell percentages among total lymphocytes.
      The CD8+DR+ cell percentage is the biological parameter most significantly
      associated with a flare (P < 0.001), even more powerful than CH50 (P < 0.01). HLA
      DR expression on CD8+ lymphocytes clearly coincided with disease evolution in
      seven patients enrolled as having quiescent disease, but who experienced one
      flare during follow-up that subsequently resolved. The percentage of circulating
      CD8+DR+ lymphocytes appears to be a biological marker which accurately reflects
      disease activity. A larger prospective study is needed to demonstrate the real
      efficacy of this marker in predicting an exacerbation in SLE patients.

PMID- 11531961
TI  - Flow cytometry: an 'old' tool for novel applications in medical genetics.
AB  - Flow cytometry was originally established as an automated method for measuring
      optical or fluorescence characteristics of cells or particles in suspension. In
      the meantime, flow cytometers have become user-friendlier, less expensive
      instruments with an increasing importance in clinical diagnostics. Besides the
      classical fields of application, such as immunophenotyping blood cells or
      analyzing the cell cycle status by measuring the DNA content, novel flow
      cytometric methods have been developed to identify and to quantify disease
      related gene sequences. Here we give an overview of current and future
      applications, including the detection of viral sequences via microsphere-based
      PCR assays and the analysis of single nucleotide polymorphisms, reflecting
      individual phenotypic traits. Furthermore, flow cytometry allows the
      quantification of gene expression changes as well as the isolation of
      differentially expressed gene sequences. Flow cytometry is also convenient for
      multiplex analyses, e.g. when hybridizing DNA samples to a mixture of various
      microsphere populations each coated with different DNA probes. Last but not
      least, the use of magnetic beads in combination with flow cytometers coupled with
      automated devices enables molecular diagnostics on a large scale. Overall, this
      review demonstrates flow cytometry as a rapid, sensitive, and reproducible tool
      applicable to a wide range of medical genetic approaches.

PMID- 11531959
TI  - Diagnostic features of pemphigus vulgaris in patients with pemphigus foliaceus:
      detection of both autoantibodies, long-term follow-up and treatment responses.
AB  - There are several studies that describe the simultaneous presence and conversion
      of pemphigus foliaceus into pemphigus vulgaris and vice versa. We describe eight
      patients with clinical, histological and immunopathological features of pemphigus
      foliaceus, at the time of the initial diagnosis. After a mean period of 2.5
      years, additional serological features of pemphigus vulgaris were observed.
      During a long-term follow-up, systemic therapies, their durations and treatment
      outcomes were recorded. These patients did not respond to conventional systemic
      therapy and developed multiple side-effects from these drugs. Hence, they were
      treated with intravenous immunoglobulin therapy (IVIg). Prior to the initiation
      of IVIg therapy, different assays were performed to detect the presence of
      autoantibodies, including indirect immunofluorescence (IIF), immunoblot assay
      using bovine gingival lysate, and ELISA. Twenty-five healthy normal individuals,
      12 patients with pemphigus vulgaris, and eight patients with pemphigus foliaceus
      served as controls for comparison of serological studies. At the time of initial
      diagnosis, the sera of all eight study patients also demonstrated binding on an
      immunoblot assay to a 160-kDa protein (desmoglein 1) only. This is typically
      observed in pemphigus foliaceus. Prior to staring IVIg therapy, binding was
      observed to both the 160 kDa and 130 kDa (desmoglein 3) proteins on an immunoblot
      assay which was characteristic of pemphigus vulgaris. The antidesmogleins, 1 and
      3 autoantibodies, were predominantly of the IgG4 subclass in all eight patients
      studied. IVIg therapy induced remission in four patients and control in four of
      the eight patients. The total follow-up period ranged from 2.6 to 9.5 years (mean
      5.3 years). It is difficult to determine the exact time at which these patients
      with pemphigus foliaceus developed pemphigus vulgaris. It is possible that the
      disease was nonresponsive to conventional immunosuppressive therapy owing to the
      simultaneous presence of two autoantibodies.

PMID- 11531965
TI  - Maternal component in the familial aggregation of hypertension.
AB  - To assess maternal versus paternal contributions to the familial aggregation of
      hypertension, we examined family history data from 344 hypertensive probands (69
      African American, 153 US Caucasian, 122 Greek Caucasian) ascertained without
      respect to parental hypertension status. The proportion of hypertensive mothers
      (81.7, 65.0 and 84.8% for African Americans, US Caucasians and Greek Caucasians,
      respectively) of these probands was significantly greater than the proportion of
      hypertensive fathers (50.0, 44.9 and 48.3%, respectively) in all three ethnic
      groups. The lifetime risk of hypertension was significantly greater for mothers
      compared with fathers of these hypertensive probands (p<0.001). Examination of
      the proband's siblings indicated that maternal history of hypertension was
      associated with greater lifetime risk for hypertension than paternal history
      (p<0.01). In conclusion, we observe a consistent maternal component in the
      inheritance of hypertension. Although we cannot separate a maternal genetic from
      epigenetic or environmental effect, our findings suggest that genetic research
      should include studies of the mitochondrial as well as nuclear genome.
      Furthermore, when assessing a patient's risk for hypertension, particular
      attention should be paid to the maternal family history.

PMID- 11531960
TI  - Dietary n-3 polyunsaturated fatty acids modulate purified murine T-cell subset
      activation.
AB  - Studies in humans and murine disease models have clearly shown dietary fish oil
      to possess anti-inflammatory properties, apparently mediated by the n-3
      polyunsaturated fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid
      (DHA). To determine the mechanisms by which dietary EPA and DHA modulate mouse T
      cell activation, female C57BL/6 mice were fed diets containing either 2%
      safflower oil (SAF), 2% fish oil (FO), or a 2% purified EPA/DHA ethyl ester
      mixture for 14 days. Splenic CD4 T cells ( approximately 90% purity) or CD8 T
      cells ( approximately 85% purity) were incubated with agonists which act at the
      plasma membrane receptor level [anti(alpha)-CD3/anti(alpha)-CD28], the
      intracellular level (PMA/Ionomycin), or at both the receptor and intracellular
      levels (alphaCD3/PMA). CD4 T cells stimulated with alphaCD3/alphaCD28 or
      PMA/Ionomycin proliferated and produced principally IL-2 (i.e. a Th1 phenotype),
      whereas the proliferation of CD4 T cells stimulated with alphaCD3/PMA was
      apparently driven principally by IL-4 (i.e. a Th2 phenotype). The IL-4 driven
      proliferation of putative Th2 CD4 cells was enhanced by dietary n-3 fatty acids
      (P = 0.02). Conversely, IL-2 production by alphaCD3/alpha CD28-stimulated CD4 T
      cells was reduced in FO-fed animals (P < 0.0001). The alphaCD3/alphaCD28
      stimulated CD8 cells cultured from FO-fed animals exhibited a significant
      decrease (P < 0.05) in proliferation. There were no dietary effects seen in
      alphaCD3/PMA-stimulated CD8 cells, which produced both IL-2 and IL-4, or in
      PMA/Ionomycin-stimulated CD8 cells, which produced principally IL-2. These data
      suggest that dietary n-3 fatty acids down-regulated IL-2 driven CD4 and CD8
      activation, while up-regulating the activation of the Th2 CD4 T-cell subset.
      Thus, the anti-inflammatory effects of n-3 fatty acids may result in both the
      direct suppression of IL-2-induced Th1 cell activation and the indirect
      suppression of Th1 cells by the enhanced cross-regulatory function of Th2 cells.

PMID- 11531967
TI  - Alpha-1-antitrypsin PI phenotypes S and Z in Europe: an analysis of the published
      surveys.
AB  - The objective of the present study was to review published surveys on allelic
      frequencies S and Z in European populations to evaluate the validity of the
      reported data. More than a hundred studies on the topic, published since 1965
      until 2000, were retrieved by Medline, Index Medicus and bibliographic references
      consultation. The criteria for studies selection were: 1) sample size> or =250
      individuals; 2) alpha-1-antitrypsin phenotype determination performed by means of
      crossed antigen-antibody or isoelectric focusing in polyacrylamide gels; 3) PI
      type determination performed without any previous screening procedure; 4) S and Z
      95% confidence interval (CI) of the reported outcomes with a calculated
      coefficient of variation <42.3 for S and <95.8 for Z; 5) S and Z 95% CI of the
      reported outcomes comprised within 95% CI limits of comparative hypothetical
      surveys designed with the same sample size of the questioned surveys and the
      highest/lowest frequencies accepted for a specific area, according to the figures
      of isogen boundary maps. Seventy studies comply with the five established
      criteria for analysis. According to the data of the selected studies, a
      geographical distribution on S and Z gene frequencies in Europe is proposed.

PMID- 11531966
TI  - Familial resemblance for glucose and insulin metabolism indices derived from an
      intravenous glucose tolerance test in Blacks and Whites of the HERITAGE Family
      Study.
AB  - Type 2 diabetes mellitus (T2DM), characterized by hyperglycemia, is a complex
      disease primarily caused by impairment in insulin sensitivity (SI) and insulin
      secretion. While a strong genetic component for T2DM is well established, there
      are few reports on racial differences in the magnitude of the genetic effects of
      T2DM and indices of glucose and insulin metabolism. We report here on the
      familial resemblance for traits related to glucose metabolism at pre-exercise
      training levels in 492 members from 99 sedentary White families and 259 members
      from 108 Black families participating in the multicenter HERITAGE Family Study.
      All these traits were obtained from the frequently sampled intravenous glucose
      tolerance test (IVGTT). They include glucose disappearance index (Kg), an overall
      index for glucose tolerance, acute insulin response to glucose (AIR(Glucose))
      which is an index for insulin secretion, and those derived from the minimal model
      including SI and the disposition index (DI). DI, derived as the product of SI and
      AIR(Glucose), is a measure of the activity of the B-cells adjusted for insulin
      resistance. After adjustment for age, sex, and body mass index, the maximal
      heritability estimates in Blacks (Whites) are 48+/-14% (25+/-8%) for Kg, 44+/-14%
      (46+/-8%) for AIR(Glucose), 38+/-12% (44+/-8%) for SI and 32+/-14% (24+/-8%) for
      DI. Interestingly, Blacks have higher heritability for overall glucose tolerance
      than Whites but there is no race difference in heritability estimates for insulin
      sensitivity or insulin secretion.

PMID- 11531968
TI  - Risk of obstetric cholestasis in sisters of index patients.
AB  - The aim of the present study was to evaluate the rate of intrahepatic cholestasis
      of pregnancy in first-degree relatives of index patients. Index patients (n=65)
      with singleton pregnancies complicated by intrahepatic cholestasis were
      identified among the women (n=11 984) who gave birth at Kuopio University
      Hospital in 1994-1998. The pregnancy histories of relatives of 56 index patients
      were reviewed and the rate of cholestasis in first-degree relatives was compared
      with that in the general obstetric population. Obstetric cholestasis was
      experienced by 9% of the parous sisters and 11% of the mothers of the index
      patients. The risk per delivery was 6% in the first-degree relatives. The rate in
      the general obstetric population was 0.54%. The odds ratios and 95% confidence
      intervals were 12.6 (5.6-28.1) for the sisters and 12.2 (6.2-24.2) for the
      mothers. Obstetric cholestasis clusters within some families and is under strong
      genetic influence, although the precise genetic pattern remains obscure. The
      sisters of index patients are at an increased risk of the disorder and may
      benefit from close obstetric care.

PMID- 11531969
TI  - Identification of fifteen novel mutations and genotype-phenotype relationship in
      Fabry disease.
AB  - Fabry disease is an X-linked recessive disorder caused by a deficiency in the
      lysosomal enzyme alpha-galactosidase A, which results in a progressive
      multisystem disease. Most families have private mutations and no general
      correlation between genotype and disease manifestations has been described to
      date. Forty-nine patients (47 males and 2 females) from 36 affected families were
      selected for the study. Their evaluation included clinical examination,
      identification of alpha-galactosidase A gene mutations and residual enzymatic
      activity. For mutation detection, each exon with flanking intronic sequences was
      amplified by polymerase chain reaction (PCR) from the patient's genomic DNA and
      sequenced. Analysis of the resulting sequences was conducted to identify
      structural defects in the gene. Each of the Fabry patients carried a mutation in
      the alpha-galactosidase A gene. Fifteen mutations were novel. They included
      missense mutations (M51K, Y123M, G261D), nonsense point mutations (E251X) and
      small insertions or deletions creating a premature translational termination
      signal (P6X, D93X, W162X, K240X, H302X, I303X, L403X, S345X, G375X, F396X).
      Residual alpha-galactosidase A activity was significantly lower in patients with
      neuropathic pain (p=0.01) and in patients with mutations leading to a
      nonconservative amino acid change (p=0.04). Our findings emphasize the wide
      variety of genetic mechanisms leading to Fabry disease. A significant genotype
      phenotype relationship was found.

PMID- 11531970
TI  - Both alleles of the M235T polymorphism of the angiotensinogen gene can be a risk
      factor for myocardial infarction.
AB  - We have studied the role of three polymorphic genes of the renin-angiotensin
      system (RAS) as independent risk factors for myocardial infarction (MI) and their
      correlation with three of the major coronary risk factors: serum cholesterol
      (CH), hypertension (HT) and smoking (SM). A population of 392 men was genotyped
      for the M235T polymorphism of the angiotensinogen (AGT) gene, the
      insertion/deletion of the angiotensin-converting enzyme (ACE) and the all66c of
      the angiotensin-II type 1 receptor (AT1R), by means of polymerase chain reaction
      (PCR) and restriction enzyme analysis. It was observed that the T allele
      frequency increased significantly in the MI with HT, CH, and SM subgroup (0.58 vs
      0.31) (p<0.01). In contrast, the M allele frequency was higher in the MI without
      HT, CH, and SM (0.69 vs 0.42) (p<0.01). A strong association between the MM
      genotype and MI (p<0.001, odds ratio=4.29, confidence interval=1.95-9.42) was
      found when age-matched MM control subjects were compared to MI individuals with
      none of the other known major coronary risk factors. Futhermore, subjects with
      the MM genotype showed a significantly higher plasma renin activity (PRA) profile
      than those with the TT genotype (p<0.001). It can be concluded that the M allele
      is an independent risk factor for MI and the T allele modified the risk when
      other major risk factors are present.

PMID- 11531971
TI  - Haplotype analysis of the USH1D locus and genotype-phenotype correlations.
AB  - Usher syndrome (USH) is characterised by hearing impairment and progressive
      pigmentary retinopathy. USH can be divided into three subtypes based on the
      severity and progression of the major clinical findings. These subtypes are
      genetically heterogeneous, with at least six loci for USH1, three for USH2 and
      one for USH3. In the present study, five unrelated consanguineous families with
      USH1 were analysed for linkage to markers flanking the six USH1 loci. Two of
      these families, one Pakistani and one Turkish, demonstrated linkage to the USH1D
      locus. In another family, haplotype segregation was consistent with linkage to
      USH1C. The remaining families were not linked to any of the six USH1 loci,
      providing support for the existence of at least one additional USH1 locus.
      Analysis of these two new USH1D families allowed us to narrow the USH1D candidate
      region to a 7.3-cM interval with a telomeric flanking marker at D10S1752.
      Comparison of the affected haplotypes in our Pakistani family with the original
      Pakistani USH1D family yielded no evidence for a founder effect. The
      identification of two additional affected families suggests that the USH1D may be
      a more common form of USH1 than originally suspected. The USH1D (CDH23) gene has
      recently been cloned. Mutation analysis has shown two different CDH23 mutations
      in the two Pakistani USH1D families studied, which confirmed our finding that
      there was no evidence for a founder effect by haplotype analysis. The interesting
      correlations between genotype and phenotype in CDH23 are also summarised.

PMID- 11531972
TI  - Co-occurrence and contribution of Fabry disease and Klippel-Trenaunay-Weber
      syndrome to a patient with atypical skin lesions.
AB  - Fabry disease (FD) is an X-linked recessive inborn error of glycosphingolipid
      metabolism. Among clinical symptoms, maculopapular skin lesions, known as
      angiokeratoma, most often appear on the lower abdomen, scrotum, and thighs, with
      a tendency toward bilateral symmetry. A 30-year-old male patient was referred to
      us for evaluation of a complex vascular and cutaneous malformation. Skin
      examination showed numerous angiokeratoma, which had developed only on the right
      part of the body, with a sharp delineation in the midline of the trunk. The
      diagnosis of FD was confirmed by demonstration of a decreased alpha-galactosidase
      A activity, and the patient was shown to be hemizygote for a missense mutation
      (R342Q) in the alpha-galactosidase A gene (GLA). This mutation was also
      demonstrated in DNA extracted from fibroblast cultures established from both
      affected and unaffected skin areas, thus excluding the hypothesis of somatic
      mosaicism or revertant mosaicism. Interestingly, the diagnosis of Klippel
      Trenaunay-Weber syndrome (KTWS) was also made, through clinical and radiological
      investigations. This is the first report on the association between FD and KTWS.
      Karyotype analysis was normal. It is likely that the mixed vascular malformations
      of KTWS affecting capillary and venous systems have contributed to the unusual
      angiokeratoma distribution pattern observed in the patient.

PMID- 11531973
TI  - Hemochromatosis mutations C282Y and H63D in 'cis' phase.
AB  - Homozygosity for the C282Y mutation of the HFE gene is a highly significant risk
      factor for the development of hereditary hemochromatosis (HH) and the majority of
      patients with HH have this genotype. An Irish/Belgian female with an elevated
      serum ferritin level and a family history of hemochromatosis was tested for the
      presence of the C282Y and H63D mutations. Results of digested PCR products have
      shown the patient to be homozygous for C282Y mutation and heterozygous for H63D
      mutation. Sequencing confirmed these findings. Genotyping of the patient's
      offspring and husband has also indicated the inheritance of both C282Y and H63D
      in 'cis'. Implications of this finding are: 1) the compound heterozygous state is
      by far the most common, but not the universal, phase for individuals found to be
      heterozygous for the two mutations, C282Y and H63D; 2) the C282Y and H63D
      mutations in the 'cis' phase may account for some cases of questionable
      parentage.

PMID- 11531974
TI  - A non-sex chromosome marker in a patient with an atypical Ullrich-Turner
      phenotype and mosaicism of 46,X,mar/46,XX.
AB  - The absence of a sex chromosome in conjunction with the presence of a marker
      chromosome generally implicates a sex chromosome origin for such marker
      chromosomes. These types of findings are frequently associated with Ullrich
      Turner syndrome. We report a patient that presented with an atypical Ullrich
      Turner phenotype and a cytogenetic mosaicism of 46,X,mar/46,XX. The marker
      chromosome was derived from chromosome 20, not from the X or Y chromosome. The
      patient's clinical features are described and discussed relative to the
      cytogenetic findings. This case further demonstrates the necessity of marker
      chromosome identification for accurate phenotype-karyotype correlation.

PMID- 11531975
TI  - De novo inverted duplication of chromosome 7(q21.3-->q35): cytogenetic diagnosis
      confirmed by FISH analysis.
AB  - We report on a newborn female patient with a de novo pure partial duplication of
      7q. The clinical features are compared with those of 19 cases from the literature
      with pure partial duplication of different segments of 7q. Conventional
      cytogenetic investigation led to the diagnosis of duplication of bands q21.3 to
      q35. This was confirmed by chromosome painting and by fluorescence in situ
      hybridization with different YAC probes from the duplicated region.

PMID- 11531976
TI  - Tetrasomy 21 due to a de novo Robertsonian translocation t(14;21) and an
      additional free trisomy 21.

PMID- 11531977
TI  - Lack of mutations in the RANK gene in Spanish patients with Paget disease of
      bone.

PMID- 11531978
TI  - Sequence microdiversity at the ribosomal RNA operons of Escherichia coli
      pyelonephritogenic strains.
AB  - OBJECTIVE: To determine whether Escherichia coli strains isolated from patients
      with uncomplicated acute pyelonephritis can be distinguished from those isolated
      from patients with complicated acute pyelonephritis on the basis of the genetic
      background. METHODS: In total, 103 E. coli strains isolated from patients with
      acute pyelonephritis (59 uncomplicated pyelonephritis (UAP) and 44 complicated
      pyelonephritis (CAP)) were characterized by RFLP of the intergenic spacer region
      16S-23S rRNA, the presence of three alternative sequences found in the
      polymorphic V6 loop of the 16S rRNA gene, the presence of the pap gene, and
      antibiotic susceptibility. RESULTS: At similarity levels of 70%, four RFLP groups
      (alpha1, alpha2, beta1 and beta2) were discerned. Strains from UAP were
      statistically significant for alpha RFLP, with a strong association with the
      presence of the pap gene, V6-I sequence and antibiotic multisensitivity. Strains
      from CAP randomly belonged to the alpha or beta RFLP groups, with a very low
      presence of the pap gene, and random presence of V6 sequences, and were
      multiresistant to antibiotics. When the CAP strains were distributed according to
      underlying pathology, non-obstructive cases had RFLP and V6 polymorphisms similar
      to those of UAP cases, while obstructive cases were clearly distinct.
      CONCLUSIONS: UAP and non-obstructive CAP E. coli strains are sensitive to
      antimicrobials, show a high level of the pap gene and belong to the selective,
      homogeneous and highly protected molecular alpha2 group, where no recombinations,
      deletions or insertions are present. On the contrary, obstructive and vesicorenal
      reflux E. coli strains show significant antimicrobial resistance, high
      intercistronic heterogenicity (wide presence of block nucleotidic substitutions,
      deletions or insertions) and significantly lower virulence.

PMID- 11531979
TI  - Evaluation of the OSIRIS video reader system for disk diffusion susceptibility
      test reading.
AB  - OBJECTIVE: The objective of this study was to compare the performance of the
      OSIRIS video-assisted reading system for disk diffusion susceptibility testing
      with conventional manual reading. METHODS: Prospectively collected clinical
      isolates (n = 119) and isolates with well-characterised resistant mechanisms,
      including extended-spectrum (ESBL) or inhibitor-resistant TEM (IRT) beta
      lactamases producing Enterobacteriaceae (80), methicillin-resistant
      Staphylococcus aureus (MRSA) (16) and vancomycin-resistant enterococci (14) were
      studied using the National Committee for Clinical Laboratory Standards disk
      diffusion technique. The OSIRIS reading (inhibition zone in mm) was compared with
      manual reading (reference value). RESULTS: Essential agreement (< or =3 mm
      discrepancy with manual reading) was 91.6% in routine isolates and 94.8% in those
      with well-characterised resistant mechanisms, respectively. Overall agreement for
      susceptibility testing interpretation was slightly higher in the former (95.5%)
      than in the latter (93.2%) group. The presence of ESBL enzymes enhanced
      variations of measurements due to synergy among amoxicillin-clavulanate and
      cephalosporins, as a consequence of closer disk placement. The poor growth
      characteristic of enterococci affected the video reading; on the other hand,
      there was a high performance with MRSA isolates. Combining all interpretative
      results, 4.1% minor, 1.0% major and 2.8% very major errors were observed.
      CONCLUSION: The OSIRIS system is a useful tool for the reading and interpretation
      of inhibition zone sizes in disk diffusion susceptibility testing.

PMID- 11531981
TI  - In vitro activity of midecamycin diacetate, a 16-membered macrolide, against
      Streptococcus pyogenes isolated in France, 1995-1999.
AB  - OBJECTIVE: To compare the in vitro activity of midecamycin diacetate to that of
      five other macrolides (erythromycin, clarithromycin, roxithromycin, azithromycin,
      and josamycin) and of clindamycin against 146 clinical isolates of Streptococcus
      pyogenes, with regard to three different phenotypes of erythromycin resistance.
      METHODS: Susceptibility pattern and resistance phenotype were determined by disk
      diffusion method and double disk test. Minimal inhibitory concentrations of
      antibiotics were obtained by the agar dilution method and evaluated according to
      the recommendations of the 'Comite de l'Antibiogramme de la Societe Francaise de
      Microbiologie' (CA-SFM). The major determinants of erythromycin resistance in S.
      pyogenes (ermB, ermTR and mefA genes) were investigated by specific amplification
      protocols. RESULTS: Most of the isolates of S. pyogenes collected during 1995-99
      were susceptible to midecamycin (93.8%), erythromycin (90.4%), clarithromycin
      (93.2%), roxithromycin (91.8%), azithromycin (88.4%), josamycin (94.5%), and
      clindamycin (94.5%). According to the CA-SFM criteria, 132 of the 146 isolates
      studied were susceptible to erythromycin (MICs < or = 1 mg/L), four were
      intermediate (MICs 2-4 mg/L), and 10 were resistant (MICs > 4 mg/L). Only nine
      isolates were midecamycin resistant (MICs > 4 mg/L), and the others were
      susceptible. The increased activity of midecamycin (MIC90 < or = 0.06 mg/L), as
      compared to erythromycin (MIC90 = 0.5 mg/L) and to other 14- or 15-membered
      macrolides, was related to the absence of the ermB determinant in seven isolates
      which displayed an efflux phenotype (five isolates) or an inducible resistance
      phenotype due to an ermTR determinant (two isolates). CONCLUSION: Midecamycin
      diacetate is active against most S. pyogenes strains isolated in France and may
      represent an attractive alternative to the treatment of streptococcal infections
      due to resistant isolates with efflux of erythromycin.

PMID- 11531980
TI  - Properties of Yersinia enterocolitica and Yersinia pseudotuberculosis in red
      blood cell concentrate of different ABO groups during 30-day storage at 4 degrees
      C.
AB  - OBJECTIVE: The present study aimed to investigate the psychrophilic properties of
      Yersinia enterocolitica and Yersinia pseudotuberculosis as contaminants of
      donated blood. METHODS: Bags with red blood cell concentrates (RBCCs) of A, B,
      and AB blood groups were inoculated with a bacterial suspension of Y.
      enterocolitica (0 : 3 and 0 : 8) and Y. pseudotuberculosis (serovars I and III)
      and stored at 4 degrees C for 30 days. Bacterial growth was measured at selected
      intervals after inoculation. Initial strains and their subcultures (isolated
      after 30 days' incubation at 4 degrees C) were tested for glycolytic activity and
      susceptibility to the bactericidal action of human serum. RESULTS: It was found
      that all strains grew well in the RBCCs of A, B, and AB groups. After incubation
      at 4 degrees C they increased their glycolytic activity and became more sensitive
      to the killing ability of human serum. CONCLUSIONS: The prolonged storage of
      contaminated Y. enterocolitica and Y. pseudotuberculosis RBCCs at 4 degrees C
      induces bacterial multiplication to high levels and stimulates glycolytic
      activity of bacterial cells.

PMID- 11531982
TI  - Clinical microbiological case: poor radiologic evolution of pulmonary
      tuberculosis in a heart transplant patient.

PMID- 11531983
TI  - Brucella detection in blood: comparison of the BacT/Alert standard aerobic
      bottle, BacT/Alert FAN aerobic bottle and BacT/Alert enhanced FAN aerobic bottle
      in simulated blood culture.
AB  - The objective of this study was to compare the performances of the standard
      aerobic bottle (StAe), FAN aerobic (FANAe) and enhanced FAN aerobic (E-FANAe)
      (the charcoal component of the FANAe was revised recently to improve the
      feasibility of Gram smear interpretation) blood culture bottles for BacT/Alert
      system for the detection of Brucella melitensis in simulated blood culture.
      Triplicate strains of eight clinical isolates of B. melitensis were studied. Each
      bottle was inoculated with 5 mL of freshly collected human blood at three
      different targeted bacterial inocula (10(1), 10(2) and 10(3) CFU/bottle). All
      bottles were monitored for up to 21 days or until they became positive. The
      results of time to detection (TTD) on the eight B. melitensis samples were as
      follows: at 10(1) CFU/bottle, the E-FANAe had a mean TTD significantly shorter
      than the StAe (48 h vs. 56.2 h, P < 0.05); and at 10(3) CFU/bottle, the FANAe and
      E-FANAe had a mean TTD significantly shorter than the StAe (41.2 h and 40 h vs.
      45.6 h, P < 0.05). The reproducibilities (no.of positive signals/no.of all
      bottles) of three bottle systems were as follows: at 10(1) CFU/bottle, the
      reproducibilities of StAe, FANAe and E-FANAe were 96, 83 and 58%, respectively.
      At 10(3) CFU/bottle, the reproducibilities of StAe, FANAe and E-FANAe were 95, 95
      and 91%, respectively. Positive results for the presence of bacteria in Gram
      smears were confirmed in 68% of StAe, 54% of FANAe and 90% of E-FANAe. In case of
      suspected brucellosis, the combination of one StAe bottle and one E-FANAe bottle
      seems to provide the highest and fastest recovery of the organism.

PMID- 11531984
TI  - Serodiagnosis of tuberculosis by enzyme immunoassay using A60 antigen.

PMID- 11531985
TI  - Effect of step-down therapy of ceftriaxone plus loracarbef versus parenteral
      therapy of ceftriaxone on the intestinal microflora in patients with community
      acquired pneumonia.

PMID- 11531986
TI  - Adherence to polystyrene of clinically relevant isolates of Candida species.

PMID- 11531987
TI  - Brucella infective endocarditis: a report of four successfully treated patients.

PMID- 11531988
TI  - Ventriculoperitoneal shunt infection caused by Staphylococcus lugdunensis.

PMID- 11531989
TI  - Bartonella henselae neuroretinitis.

PMID- 11531991
TI  - Recurrent bacteremia by Chryseobacterium indologenes in an oncology patient with
      a totally implanted intravascular device.
AB  - Chryseobacterium indologenes was isolated from the blood cultures of an
      oncological patient with a totally implantable device. Because a catheter-related
      infection was suspected, the Port-A-Cath was removed after a 10-day course of
      piperacillin-tazobactam. Differences in susceptibility may exist if either the
      criteria for either Pseudomonas or Enterobacteriaceae are used.

PMID- 11531990
TI  - Polyclonal Staphylococcus epidermidis intravascular catheter-related infections.
AB  - During a 4-month period we prospectively investigated the frequency of polyclonal
      catheter infections with Staphylococcus epidermidis. Of each catheter with pure
      growth of S. epidermidis, six colonies were genotypically analyzed with pulsed
      field gel electrophoresis. Two out of 12 patients with catheter infection had a
      polyclonal infection. Both clones of each catheter had a clearly different
      antibiotic susceptibility. This study shows that polyclonal catheter infections
      are not exceptional. Further studies are needed to define the clinical
      consequences of polyclonal catheter infection.

PMID- 11531992
TI  - Decline of a visceral leishmaniasis epidemic in HIV-infected patients after the
      introduction of highly active antiretroviral therapy (HAART).

PMID- 11531993
TI  - Azithromycin in healthy adults?

PMID- 11531997
TI  - Mapping divalent metal ion binding sites in a group II intron by Mn(2+)- and
      Zn(2+)-induced site-specific RNA cleavage.
AB  - The function of group II introns depends on positively charged divalent metal
      ions that stabilize the ribozyme structure and may be directly involved in
      catalysis. We investigated Mn2+- and Zn2+-induced site-specific RNA cleavage to
      identify metal ions that fit into binding pockets within the structurally
      conserved bI1 group II intron domains (DI-DVI), which might fulfill essential
      roles in intron function. Ten cleavage sites were identified in DI, two sites in
      DIII and two in DVI. All cleavage sites are located in the center or close to
      single-stranded and flexible RNA structures. Strand scissions mediated by
      Mn2+/Zn2+ are competed for by Mg2+, indicating the existence of Mg2+ binding
      pockets in physical proximity to the observed Mn2+-/Zn2+-induced cleavage
      positions. To distinguish between metal ions with a role in structure
      stabilization and those that play a more specific and critical role in the
      catalytic process of intron splicing, we combined structural and functional
      assays, comparing wild-type precursor and multiple splicing-deficient mutants. We
      identified six regions with binding pockets for Mg2+ ions presumably playing an
      important role in bI1 structure stabilization. Remarkably, assays with DI
      deletions and branch point mutants revealed the existence of one Mg2+ binding
      pocket near the branching A, which is involved in first-step catalysis. This
      pocket formation depends on precise interaction between the branching nucleotide
      and the 5' splice site, but does not require exon-binding site 1/intron binding
      site 1 interaction. This Mg2+ ion might support the correct placing of the
      branching A into the 'first-step active site'.

PMID- 11531998
TI  - Escherichia coli RNA polymerase subunit omega and its N-terminal domain bind full
      length beta' to facilitate incorporation into the alpha2beta subassembly.
AB  - The omega subunit of Escherichia coli RNA polymerase, consisting of 90 amino
      acids, is present in stoichiometric amounts per molecule of core RNA polymerase
      (alpha2betabeta'). The presence of omega is necessary to restore denatured RNA
      polymerase in vitro to its fully functional form, and, in an omega-less strain of
      E. coli, GroEL appears to substitute for omega in the maturation of RNA
      polymerase. The X-ray structure of Thermus aquaticus core RNA polymerase suggests
      that two regions of omega latch on to beta' at its N-terminus and C-terminus. We
      show here that omega binds only the intact beta' subunit and not the beta' N
      terminal domain or beta' C-terminal domain, implying that omega binding requires
      both these regions of beta'. We further show that omega can prevent the
      aggregation of beta' during its renaturation in vitro and that a V8-protease
      resistant 52-amino-acid-long N-terminal domain of omega is sufficient for binding
      and renaturation of beta'. CD and functional assays show that this N-terminal
      fragment retains the structure of native omega and is able to enhance the
      reconstitution of core RNA polymerase. Reconstitution of core RNA polymerase from
      its individual subunits proceeds according to the steps alpha + alpha --> alpha2
      + beta --> alpha2beta + beta' --> alpha2betabeta'. It is shown here that omega
      participates during the last stage of enzyme assembly when beta' associates with
      the alpha2beta subassembly.

PMID- 11531996
TI  - A novel heat stress-responsive gene in the marine diatom Chaetoceros compressum
      encoding two types of transcripts, a trypsin-like protease and its related
      protein, by alternative RNA splicing.
AB  - We investigated the change of mRNA expression patterns in the laboratory-grown
      diatom Chaetoceros compressum under heat-stress conditions by mRNA arbitrarily
      primed (RAP) RT-PCR. Cells grown at 20 degrees C were subjected to heat treatment
      at 30 degrees C for 15 min and subsequently maintained at 20 degrees C for 8 h.
      Four genes including HI-5 were detected as heat stress-responsive genes by
      fingerprint analysis of RAP RT-PCR. Cloning for full-length cDNA sequences of HI
      5 transcripts and related genomic DNA analysis revealed that two types of mRNA,
      HI-5a and HI-5b, were transcribed from the single HI-5 gene. While the HI-5a
      protein contained a catalytic domain characteristic to trypsin-like proteases,
      the HI-5b protein lacked this domain due to an insertion in the associated mRNA
      of 112 nucleotides; this insertion sequence contained a stop codon near the
      central region. Quantitative RT-PCR was performed to investigate the changes in
      expression levels of the two types of mRNA following heat treatment. The HI-5b
      transcripts were constitutively expressed in both unstressed and heat-stressed
      cells. In contrast, the number of HI-5a transcripts markedly increased in cells
      immediately after heat stress, reaching levels 19-fold higher at 8 h after heat
      stress than that in unstressed cells. These results suggest that RNA splicing
      plays a key role in heat stress-dependent expression of the HI-5a and HI-5b
      transcripts from the single HI-5 gene in the diatom.

PMID- 11531999
TI  - Biosynthesis of (1-->3)-beta-D-glucan (callose) by detergent extracts of a
      microsomal fraction from Arabidopsis thaliana.
AB  - The aim of this work was to develop a biochemical approach to study (1-->3)-beta
      D-glucan (callose) biosynthesis using suspension cultures of Arabidopsis
      thaliana. Optimal conditions for in vitro synthesis of callose corresponded to an
      assay mixture containing 50 mM Mops buffer, pH 6.8, 1 mM UDP-glucose, 8 mM Ca2+
      and 20 mM cellobiose. The enzyme was Ca2+-dependent, and addition of Mg2+ to the
      reaction mixture did not favour cellulose biosynthesis. Enzyme kinetics suggested
      the existence of positive homotropic cooperativity of (1-->3)-beta-D-glucan
      synthase for the substrate UDP-glucose, in agreement with the hypothesis that
      callose synthase consists of a multimeric complex containing several catalytic
      subunits. Detergents belonging to different families were tested for their
      ability to extract and preserve membrane-bound (1-->3)-beta-D-glucan synthase
      activity. Cryo-transmission electron microscopy experiments showed that n-octyl
      beta-D-glucopyranoside allowed the production of micelle-like structures, whereas
      vesicles were obtained with Chaps and Zwittergent 3-12. The morphology and size
      of the (1-->3)-beta-D-glucans synthesized in vitro by fractions obtained with
      different detergents were affected by the nature of the detergent tested. These
      data suggest that the general organization of the glucan synthase complexes and
      the properties of the in vitro products are influenced by the detergent used for
      protein extraction. The reaction products synthesized by different detergent
      extracts were characterized by infrared spectroscopy, methylation analysis, 13C
      NMR spectroscopy, electron microscopy and X-ray diffraction. These products were
      identified as linear (1-->3)-beta-D-glucans having a degree of polymerization
      higher than 100, a microfibrillar structure, and a low degree of crystallinity.

PMID- 11532000
TI  - Mutational analysis of the J recombination signal sequence binding protein (RBP
      J)/Epstein-Barr virus nuclear antigen 2 (EBNA2) and RBP-J/Notch interaction.
AB  - Epstein-Barr virus nuclear antigen 2 (EBNA2) and the Notch protein both function
      within the nucleus as transcriptional adaptor proteins. EBNA2 plays a key role
      during the immortalization of primary B-cells by Epstein-Barr virus (EBV). Notch
      proteins are involved in lymphomagenesis as well as in multiple cell fate
      decisions during tissue differentiation and development. Both, EBNA2 and Notch
      interact with the DNA binding protein RBP-J and thereby gain access to the
      promoter of their target genes. In order to identify regions within the J
      recombination signal sequence binding protein (RBP-J), that are relevant for
      either the Notch or the EBNA2 interaction, we have performed a mutational
      analysis of RBP-J. A library of RBP-J mutants was screened by a reverse two
      hybrid system for alleles that fail to bind to either EBNA2 or Notch. The
      sequence analysis of these alleles reveals that a limited and particularly
      distinct number of amino-acid positions are relevant for either interaction only.
      Given the important role of RBP-J in B-cell immortalization, the EBNA2/RBP-J
      protein-protein interaction could be a candidate target for therapeutic
      intervention in EBV related diseases.

PMID- 11532001
TI  - The role of Thr160 phosphorylation of Cdk2 in substrate recognition.
AB  - Full activation of cyclin-dependent kinases (Cdks) requires binding to a cyclin
      and phosphorylation on an activating site equivalent to Thr160 in Cdk2 by the Cdk
      activating kinase. Much is known about the effects of cyclin binding, but the
      role of the activating phosphorylation is less well understood. We have
      characterized the effects of Thr160 phosphorylation of Cdk2 on its interactions
      with substrates, particularly with the P + 3 position. We find that an ionic
      interaction participates in the recognition of the P + 3 position of the
      substrate and confirms an observation from structural studies indicating that a
      key element of this recognition is an interaction between the lysine at the P + 3
      position and the Thr160 phosphate of Cdk2. The major effect of disrupting the
      lysine-phosphate interaction was on kcat values rather than Km values, suggesting
      that the energy from this interaction is used to align the substrate for
      efficient catalysis. A lack of effect of Thr160 phosphorylation on the ATPase
      activity of Cdk2 supported this interpretation.

PMID- 11532002
TI  - Alternate routes to conformational specificity in a Greek key beta barrel
      protein.
AB  - The N-terminal domain of protein S, a Greek key calcium-binding protein from
      Myxococcus xanthus, forms an atypical molten globule in the calcium-free state.
      The structure of this state is characterized by significant conformational
      fluctuations, which are localized to a subdomain that is not contiguous along the
      polypeptide chain. The conformational instability of this subdomain appears to
      arise from repulsive electrostatic interactions of four acidic side chains that
      are clustered together but are removed from the calcium-binding sites. This
      domain can be induced to form a native-like state through two different routes,
      calcium binding or reduction of pH. Acid-induced folding stabilizes the locally
      unfolded subdomain by selectively removing repulsive interactions without
      significantly affecting global stability. In contrast, calcium binding appears to
      increase local stability indirectly by causing global stabilization.

PMID- 11532003
TI  - Cytosolic chaperonin-containing t-complex polypeptide 1 changes the content of a
      particular subunit species concomitant with substrate binding and folding
      activities during the cell cycle.
AB  - The chaperonin-containing t-complex polypeptide 1 (CCT) is a cytosolic molecular
      chaperone composed of eight subunits that assists in the folding of actin,
      tubulin and other cytosolic proteins. We show here that the content of particular
      subunits of CCT within mammalian cells decreases concomitantly with the reduction
      of chaperone activity during cell cycle arrest at M phase. CCT recovers chaperone
      activity upon resumption of these subunits after release from M phase arrest or
      during arrest at S phase. The levels of alpha, delta and zeta-1 subunits
      decreased more rapidly than the other subunits during M phase arrest by colcemid
      treatment and recovered after release from the arrest. Gel filtration
      chromatography or native (nondenaturing) PAGE analysis followed by immunoblotting
      indicated that the alpha and delta subunit content in the 700- to 900-kDa CCT
      complex was appreciably lower in the M phase cells than in asynchronous cells. In
      vivo, the CCT complex of M-phase-arrested cells was found to bind lower amounts
      of tubulin than that of asynchronous cells. In vitro, the CCT complex of M phase
      arrested cells was less active in binding and folding denatured actin than that
      of asynchronous cells. On the other hand, the CCT complex of asynchronous cells
      (a mixture of various phases of cell cycle) exhibited lower alpha and delta
      subunit content and lower chaperone activity than that of S-phase-arrested cells
      obtained by excess thymidine treatment. In addition, turnover (synthesis and
      degradation) rates of the alpha and delta subunits in vivo were more rapid than
      those of most other subunits. These results suggest that the content of alpha and
      delta subunits of CCT reduces from the complete active complex in S phase cells
      to incomplete inactive complex in M phase cells.

PMID- 11532004
TI  - Functional analysis of polar amino-acid residues in membrane associated regions
      of the NHE1 isoform of the mammalian Na+/H+ exchanger.
AB  - The NHE1 isoform of the Na+/H+ exchanger is a ubiquitous plasma membrane protein
      that regulates intracellular pH in mammalian cells. Site-specific mutagenesis was
      used to examine the functional role of conserved, polar amino-acid residues
      occurring in segments of the protein associated with the membrane. Seventeen
      mutant proteins were assessed by characterization of intracellular pH changes in
      stably transfected cells that lacked an endogenous Na+/H+ exchanger. All of the
      mutant proteins were targeted correctly to the plasma membrane and were expressed
      at similar levels. Amino-acid residues Glu262 and Asp267 were critical to Na+/H+
      exchanger activity while mutation of Glu391 resulted in only a partial reduction
      in activity. The Glu262-->Gln mutant was expressed partially as a deglycosylated
      protein with increased sensitivity to trypsin treatment in presence of Na+.
      Substitution of mutated Glu262, Asp267 and Glu391 with alternative acidic
      residues restored Na+/H+ exchanger activity. The Glu262-->Asp mutant had a
      decreased affinity for Li+, but its activity for Na+ and H+ ions was unaffected.
      The results support the hypothesis that side-chain oxygen atoms in a few,
      critically placed amino acids are important in Na+/H+ exchanger activity and the
      acidic amino-acid residues at positions 262, 267 and 391 are good candidates for
      being involved in Na+ coordination by the protein.

PMID- 11532005
TI  - Irreversible inhibition of pig kidney copper-containing amine oxidase by sodium
      and lithium ions.
AB  - Copper amine oxidase was found to be inhibited in a complex way by small alkali
      metal ions. Classic enzyme kinetic studies showed that Li+ and Na+ were weak
      noncompetitive inhibitors, whereas the larger alkali metals K+, Rb+ and Cs+ were
      not inhibitors. However, freezing in the presence of Na+ or Li+ surprisingly
      resulted in complete and irreversible inactivation. In the case of Li+, it was
      possible to show that one ion per subunit was retained permanently in the
      inactivated enzyme, suggesting a structural rearrangement. The mechanism of
      inhibition was studied using a wide range of spectroscopic and analytic
      techniques. Only minor changes in the protein structure could be detected, except
      for a significant change in the geometry of the copper site. The unique
      topaquinone cofactor was apparently functional and able to proceed through the
      reductive half of the catalytic cycle, but the enzyme no longer reacted with
      oxygen. The effect of Na+ and Li+ was source-specific for pig kidney and bovine
      kidney amine oxidases, while the enzymes from bovine serum or plants were not
      inactivated, consistent with a mechanism dependent on small structural
      differences. A model for irreversible inactivation is proposed in which the
      cofactor is co-ordinated directly to copper, in analogy with the inactivation
      reported for Escherichia coli amine oxidase under crystal growth conditions.

PMID- 11532006
TI  - Structural analysis of the polysaccharide from the lipopolysaccharide of
      Porphyromonas gingivalis strain W50.
AB  - The lipopolysaccharide (LPS) of Porphyromonas gingivalis is an important pro
      inflammatory molecule in periodontal disease and a significant target of the
      host's specific immune response. In addition, we recently demonstrated using
      monoclonal antibodies that the Arg-gingipains of P. gingivalis are post
      translationally modified with glycan chains that are immunologically related to
      an LPS preparation from this organism. In the present investigation, we
      determined the structure of the O-polysaccharide of P. gingivalis W50 that was
      fully characterized on the basis of 1D and 2D NMR (DQF-COSY, TOCSY, NOESY, ROESY,
      1H-13C HSQC and 1H-31P HXTOCSY) and GC-MS data. These data allowed us to conclude
      that the O-polysaccharide is built up of the tetrasaccharide repeating sequence: 
      ->6)-alpha-D-Glcp-(1-->4)-alpha-L-Rhap-(1-->3)-beta-D-GalNAc-(1-->3)-alpha-D-Galp
      (1--> and carries a monophosphoethanolamine residue at position C-2 of the alpha
      rhamnose residue in a nonstoichiometric (approximately 60%) amount. These data
      indicate that the O-polysaccharide of P. gingivalis LPS is composed of an
      unusually modified tetrasaccharide repeating unit.

PMID- 11532007
TI  - Structural analysis of the lipopolysaccharide core of a rough, cystic fibrosis
      isolate of Pseudomonas aeruginosa.
AB  - Lipopolysaccharide (LPS) expressed by isolates of Pseudomonas aeruginosa from
      cystic fibrosis patients lacks the O-polysaccharide chain but the degree to which
      the rest of the molecule changes has not been determined. We analyzed, for the
      first time, the core structure of an LPS from a rough, cystic fibrosis isolate of
      P. aeruginosa. The products of mild acid hydrolysis and strong alkaline
      degradation of the LPS were studied by ESI MS, MALDI MS, and NMR spectroscopy.
      The following structure was determined for the highest-phosphorylated core-lipid
      A backbone oligosaccharide isolated after alkaline deacylation of the LPS:
      [structure: see text] where Kdo and Hep are 3-deoxy-D-manno-octulosonic acid and
      L-glycero-D-manno-heptose, respectively; all sugars are in the pyranose form and
      have the D configuration unless stated otherwise. The outer core region occurs as
      two isomeric glycoforms differing in the position of rhamnose (Rha). The inner
      core region carries four phosphorylation sites at two Hep residues, HepI being
      predominantly bisphosphorylated and HepII monophosphorylated. In the intact LPS,
      both Hep residues carry monophosphate and diphosphate groups in nonstoichiometric
      quantities, GalN is N-acylated by an L-alanyl group, HepII is 7-O-carbamoylated,
      and the outer core region is nonstoichiometrically O-acetylated at four sites.
      Therefore, the switch to the LPS-rough phenotype in cystic fibrosis isolates of
      P. aeruginosa is not accompanied by losses of core monosaccharide, phosphate or
      acyl components. The exact positions of the O-acetyl groups and the role of the
      previously undescribed O-acetylation in the LPS core of P. aeruginosa remain to
      be determined.

PMID- 11532008
TI  - Phytochrome Cph1 from the cyanobacterium Synechocystis PCC6803. Purification,
      assembly, and quaternary structure.
AB  - The phytochrome Cph1 from the cyanobacterium Synechocystis PCC6803 forms
      holoprotein adducts with close spectral similarity to plant phytochromes when
      autoassembled in vitro with bilin chromophores. Cph1 is a 85-kDa protein that
      acts as a light-regulated histidine kinase seemingly involved in 'two-component'
      signalling. This paper describes the improvement of Cph1 purification, estimation
      of the extinction coefficient of holo-Cph1, spectral analyses of the assembly
      procedure and studies on quaternary structure. During assembly with the natural
      chromophore phycocyanobilin (PCB), a red-shifted intermediate is observed. A
      similar result was obtained when phycoerythrobilin was used as chromophore. As
      shown by SDS/PAGE and Zn2+ fluorescence, the covalent attachment of PCB is
      blocked by 1 mM iodoacetamide, a cysteine-derivatizing agent. When PCB was
      incubated with blocked apo-Cph1, again a shoulder at longer wavelengths appeared.
      It is therefore proposed that the long-wavelength-absorbing form represents the
      protonated, noncovalently bound bilin. Biliverdin, which is neither protonated
      nor covalently attached, undergoes spectral changes in its blue-absorbing band
      upon incubation with apo-Cph1. On the basis of these data we therefore propose a
      three-step model for phytochrome autoassembly. Size-exclusion chromatography
      revealed different mobilities for the apoprotein, red-absorbing Cph1-PCB and far
      red-absorbing Cph1-PCB. The major peaks of both holoprotein adducts had apparent
      molecular masses approximately 200 kDa, a result in agreement with the notion
      that autophosphorylation in sensory histidine kinases requires dimerization. When
      Cph1-PCB was further purified by preparative native electrophoresis, the mobility
      on size-exclusion chromatography was approximately 100 kDa, and it was found to
      have lost its kinase activity, results implying that the material had lost its
      capacity to dimerize.

PMID- 11532009
TI  - Chemosensory protein from the moth Mamestra brassicae. Expression and secondary
      structure from 1H and 15N NMR.
AB  - A group of ubiquitous small proteins (average 13 kDa) has been isolated from
      several sensory organs of a wide range of insect species. They are believed to be
      involved in chemical communication and perception (olfaction or taste) and have
      therefore been called chemo-sensory proteins (CSPs). Several CSPs have been
      identified in the antennae and proboscis of the moth Mamestra brassicae. We have
      expressed one of the antennal proteins (CSPMbraA6) in large quantities as a
      soluble recombinant protein in Escherichia coli periplasm. This 112-residue
      protein is a highly soluble monomer of 13 072 Da with a pI of 5.5. NMR data (1H
      and 15N) indicate that CSPMbraA6 is well folded and contains seven alpha helices
      (59 amino acids) and two short extended structures (12 amino acids) from
      positions 5 to 10 and from 107 to 112. Thirty-seven amino acids are involved in
      beta turns and coiled segments and four amino acids are not assigned in the NMR
      spectra (the N-terminus and the residue 52 in the loop 48-53), probably due to
      their mobility. This is the first report on the expression and structural
      characterization of a recombinant CSP.

PMID- 11532010
TI  - A novel hyperthermophilic archaeal glyoxylate reductase from Thermococcus
      litoralis. Characterization, gene cloning, nucleotide sequence and expression in
      Escherichia coli.
AB  - A novel NADH-dependent glyoxylate reductase has been found in a hyperthermophilic
      archaeon Thermococcus litoralis DSM 5473. This is the first evidence for
      glyoxylate metabolism and its corresponding enzyme in hyperthermophilic archaea.
      NADH-dependent glyoxylate reductase was purified approximately 560-fold from a
      crude extract of the hyperthermophile by five successive column chromatographies
      and preparative PAGE. The molecular mass of the purified enzyme was estimated to
      be 76 kDa, and the enzyme consisted of a homodimer with a subunit molecular mass
      of approximately 37 kDa. The optimum pH and temperature for enzyme activity were
      approximately 6.5 and 90 degrees C, respectively. The enzyme was extremely
      thermostable; the activity was stable up to 90 degrees C. The glyoxylate
      reductase catalyzed the reduction of glyoxylate and hydroxypyruvate, and the
      relative activity for hydroxypyruvate was approximately one-quarter that of
      glyoxylate in the presence of NADH as an electron donor. NADPH exhibited rather
      low activity as an electron donor compared with NADH. The Km values for
      glyoxylate, hydroxypyruvate, and NADH were determined to be 0.73, 1.3 and 0.067
      mM, respectively. The gene encoding the enzyme was cloned and expressed in
      Escherichia coli. The nucleotide sequence of the glyoxylate reductase gene was
      determined and found to encode a peptide of 331 amino acids with a calculated
      relative molecular mass of 36,807. The amino-acid sequence of the T. litoralis
      enzyme showed high similarity with those of probable dehydrogenases in Pyrococcus
      horikoshii and P. abyssi. The purification of the enzyme from recombinant E. coli
      was much simpler compared with that from T. litoralis; only two steps of heat
      treatment and dye-affinity chromatography were needed.

PMID- 11532011
TI  - Identification of a novel heterodimeric outer membrane protein of Porphyromonas
      gingivalis by two-dimensional gel electrophoresis and peptide mass
      fingerprinting.
AB  - Porphyromonas gingivalis is a Gram-negative, anaerobic bacterium associated with
      chronic periodontitis. A 2D electrophoretic analysis of the outer membrane of P.
      gingivalis W50 revealed a dominant train of spots at 40-41 kDa. The proteins in
      the train of spots were digested in-gel with trypsin and identified by MS. The
      train of spots represented two proteins, designated Omp40 and Omp41 that share
      47% sequence identity. Preparation of outer membranes in the absence of protease
      inhibitors resulted in partial cleavage of Omp40 and Omp41 to produce an N
      terminal and C-terminal fragment of both proteins. The N-terminal fragments
      displayed the same isoelectric heterogeneity as the intact proteins. Almost 100%
      of the amino-acid sequence of these N-terminal fragments in each 2D gel spot was
      verified suggesting lack of post-translational modification. Re-subjecting a
      single N-terminal domain spot to 2D electrophoresis resulted in the complete
      series of spots being reproduced, suggesting that the heterogeneity was related
      to conformational equilibria. Under reduced conditions and without heating, Omp40
      and Omp41 migrated as 34- to 35-kDa proteins in SDS/PAGE whereas under nonreduced
      conditions the proteins migrated as 70-kDa proteins, suggesting the formation of
      dimers through intersubunit disulfide bonds. The proteins each contain two
      cysteine residues in the conserved sequence RPVSCPECPE. Tryptic peptides
      generated from the nonreduced forms of the proteins confirmed the presence of
      heterodimers stabilized through intersubunit disulfide bond formation. With the
      exception of heterodimer formation, the two proteins share several similarities
      with OmpA-like porins of other Gram-negative bacteria including consensus
      sequence, abundance, modification by heat, overall length and positioning of
      domains.

PMID- 11532012
TI  - ADAM-HCV, a new-concept diagnostic assay for antibodies to hepatitis C virus in
      serum.
AB  - We screened phage libraries using sera from noninfected individuals and patients
      infected by hepatitis C virus (HCV). By applying different selection and
      maturation strategies, we identified a wide collection of efficient phage-borne
      ligands for HCV-specific antibodies. The selected ligands retained their
      antigenic properties when expressed as multimeric synthetic peptides. Peptides
      that mimic several immunodominant epitopes of the virus were used to develop a
      novel type of diagnostic assay which efficiently detects antibodies to HCV in
      serum. This type of analysis provides a conclusive diagnosis for many patients
      identified as indeterminate according to presently available serological assays.

PMID- 11532013
TI  - Characterization of the formyltransferase from Methylobacterium extorquens AM1.
AB  - Methylobacterium extorquens AM1 possesses a formaldehyde-oxidation pathway that
      involves enzymes with high sequence identity with enzymes from methanogenic and
      sulfate-reducing archaea. Here we describe the purification and characterization
      of formylmethanofuran-tetrahydromethanopterin formyltransferase (Ftr), which
      catalyzes the reversible formation of formylmethanofuran (formylMFR) and
      tetrahydromethanopterin (H4MPT) from N5-formylH4MPT and methanofuran (MFR).
      Formyltransferase from M. extorquens AM1 showed activity with MFR and H4MPT
      isolated from the methanogenic archaeon Methanothermobacter marburgensis
      (apparent Km for formylMFR = 50 microM; apparent Km for H4MPT = 30 microM). The
      enzyme is encoded by the ffsA gene and exhibits a sequence identity of
      approximately 40% with Ftr from methanogenic and sulfate-reducing archaea. The 32
      kDa Ftr protein from M. extorquens AM1 copurified in a complex with three other
      polypeptides of 60 kDa, 37 kDa and 29 kDa. Interestingly, these are encoded by
      the genes orf1, orf2 and orf3 which show sequence identity with the formylMFR
      dehydrogenase subunits FmdA, FmdB and FmdC, respectively. The clustering of the
      genes orf2, orf1, ffsA, and orf3 in the chromosome of M. extorquens AM1 indicates
      that, in the bacterium, the respective polypeptides form a functional unit.
      Expression studies in Escherichia coli indicate that Ftr requires the other
      subunits of the complex for stability. Despite the fact that three of the
      polypeptides of the complex showed sequence similarity to subunits of Fmd from
      methanogens, the complex was not found to catalyze the oxidation of formylMFR.
      Detailed comparison of the primary structure revealed that Orf2, the homolog of
      the active site harboring subunit FmdB, lacks the binding motifs for the active
      site cofactors molybdenum, molybdopterin and a [4Fe-4S] cluster. Cytochrome c was
      found to be spontaneously reduced by H4MPT. On the basis of this property, a
      novel assay for Ftr activity and MFR is described.

PMID- 11532014
TI  - Functional asymmetry of the ATP-binding-cassettes of the ABC transporter TAP is
      determined by intrinsic properties of the nucleotide binding domains.
AB  - The ATP-binding-cassette (ABC) transporter associated with antigen processing
      (TAP) delivers peptides into the ER. TAP consists of two polypeptides (TAP1 and
      TAP2) each with an N-terminal transmembrane (TMD) and a C-terminal nucleotide
      binding domain (NBD). The two highly homologous NBDs of TAP show different
      nucleotide binding specificites, and identical mutations in the domains can have
      different effects on peptide transport. We asked whether this functional
      asymmetry of the NBDs is an intrinsic property or is imposed by the TMDs to which
      they are linked. To investigate the functional interdependence of the TAP
      domains, we created various TAP variants in which TMDs and/or NBDs were
      exchanged. All TAP variants except those with two TMDs of TAP1 could assemble.
      The TMDs did not affect the different nucleotide binding properties of the NBDs.
      The TAP variant with switched NBDs showed active peptide transport while the
      variants with pairs of identical NBDs or TMDs were inactive. Although both types
      of TMDs and NBDs have to be present for peptide transport they do not have to be
      assorted as in wild-type TAP. Thus, TAP domains seem to preserve functional
      autonomy despite their fusion into single polypeptide chains. We propose that the
      two NBDs act as nonequivalent 'modules' that directly determine the functional
      asymmetry of the included ATP-binding-cassettes. This provides a new insight into
      the function of NBDs and opens up new possibilities to investigate the molecular
      mechanism of the 'NBD engine' in ABC transporters.

PMID- 11532015
TI  - Oxidation of hydroquinones by the versatile ligninolytic peroxidase from
      Pleurotus eryngii. H2O2 generation and the influence of Mn2+.
AB  - Formation of H2O2 during the oxidation of three lignin-derived hydroquinones by
      the ligninolytic versatile peroxidase (VP), produced by the white-rot fungus
      Pleurotus eryngii, was investigated. VP can oxidize a wide variety of phenols,
      including hydroquinones, either directly in a manner similar to horseradish
      peroxidase (HRP), or indirectly through Mn3+ formed from Mn2+ oxidation, in a
      manner similar to manganese peroxidase (MnP). From several possible buffers (all
      pH 5), tartrate buffer was selected to study the oxidation of hydroquinones as it
      did not support the Mn2+-mediated activity of VP in the absence of exogenous H2O2
      (unlike glyoxylate and oxalate buffers). In the absence of Mn2+, efficient
      hydroquinone oxidation by VP was dependent on exogenous H2O2. Under these
      conditions, semiquinone radicals produced by VP autoxidized to a certain extent
      producing superoxide anion radical (O2*-) that spontaneously dismutated to H2O2
      and O2. The use of this peroxide by VP produced quinone in an amount greater than
      equimolar to the initial H2O2 (a quinone/H2O2 molar ratio of 1 was only observed
      under anaerobic conditions). In the presence of Mn2+, exogenous H2O2 was not
      required for complete oxidation of hydroquinone by VP. Reaction blanks lacking VP
      revealed H2O2 production due to a slow conversion of hydroquinone into
      semiquinone radicals (probably via autooxidation catalysed by trace amounts of
      free metal ions), followed by O2*- production through semiquinone autooxidation
      and O2*- reduction by Mn2+. This peroxide was used by VP to oxidize hydroquinone
      that was mainly carried out through Mn2+ oxidation. By comparing the activity of
      VP to that of MnP and HRP, it was found that the ability of VP and MnP to oxidize
      Mn2+ greatly increased hydroquinone oxidation efficiency.

PMID- 11532016
TI  - Bacterial expression and conformational analysis of a chemosensory protein from
      Schistocerca gregaria.
AB  - Chemosensory proteins (CSPs) are a class of small, soluble proteins present at
      high concentrations in chemosensory organs of different insect species. Several
      pieces of evidence suggest their involvement in carrying chemical messages from
      the environment to chemosensory receptors. However, a structural description of
      the mechanism of delivery has not been reported. In order to provide the first
      detailed conformational characterization of these molecules, we cloned a specific
      isoform (CSP-sg4) from Schistocerca gregaria and expressed it in Escherichia
      coli. The product was obtained with yields of more than 20 mg per L of culture,
      all in its soluble form. The recombinant protein was identical to the native one
      with respect to pairing of the disulfide bridges, aggregative state and secondary
      structure elements. Structural investigations revealed a significantly stable
      polypeptide with respect to variations in temperature and acidity. CD analysis,
      preliminary NMR data and secondary structure prediction pointed to a correctly
      folded structure where helical regions and loops are alternated in a similar
      fashion as that observed for other classes of odorant- and pheromone-binding
      proteins presenting no sequence similarity to CSPs.

PMID- 11532017
TI  - Role of beta isoform-specific insertions of Ca2+/calmodulin-dependent protein
      kinase II.
AB  - Alpha and beta isoforms of Ca2+/calmodulin-dependent protein kinase II (alpha and
      beta CaM kinase II, respectively) are highly conserved except for beta-specific
      insertions 1 and 2, located at amino acids 316-340 and 354-392, respectively. To
      investigate the role of these beta-specific insertions, we prepared the deletion
      mutants betaDelta1, betaDelta2 and betaDelta1/2, which lacked insertions 1, 2 and
      both, respectively. These mutant DNAs were expressed in neuroblastoma cells and
      compared with the wild-type enzyme. Green fluorescent protein tagged CaM kinase
      II was used to further explore the distribution of the kinase in living cells.
      Most (80%) of wild-type beta and mutant betaDelta1 were located in the
      particulate fraction, and distributed in the cell body and neurites, forming
      punctate or spot-like structures in the neurites. Mutants betaDelta2 and
      betaDelta1/2 were distributed in almost equal amounts in the soluble and
      particulate fractions. They were concentrated in the base of neurites and only
      partlially distributed throughout neurites, indicating that their transport to
      neurites was impaired. Beta(1-410), a deletion mutant of the association domain
      with a monomeric form, was located primarily in the soluble fraction. These
      results indicate that insertion 2, the association domain, and the oligomeric
      form of beta CaM kinase II play an important role in the cellular distribution of
      beta CaM kinase II.

PMID- 11532018
TI  - Specific inhibition of interleukin-4-dependent Stat6 activation by an
      intracellularly delivered peptide.
AB  - The transcription factor Stat6 (signal transducer and activator of transcription
      6) is activated following stimulation with interleukin (IL)-4 or IL-13. Stat6
      binds via a single SH2 domain first to tyrosine-phosphorylated motifs in the IL
      4Ralpha chain, and then to another Stat6 molecule, which results in the formation
      of active dimers. We show here that a peptide derived from the Stat6-binding
      region of IL-4Ralpha (Stat6BP) is an effective inhibitor when it is delivered
      into cells by coupling with a membrane-permeable peptide. Stat6BP completely
      inhibited IL-4 dependent phosphorylation of Stat6, as well as basal and IL-4
      stimulated transcription from a reporter gene construct with a Stat6-dependent
      promoter, while IL-3 and IL-4 dependent phosphorylation of Stat5 was not
      affected. The inhibitory effect of Stat6BP was transient, but could be prolonged
      by treating the cells with the phosphatase inhibitor pervanadate.

PMID- 11532019
TI  - PCR-RFLP typing detects new HLA-DRB1 alleles: DRB1*13022, DRB1*1336 and
      DRB1*1435.
AB  - It is difficult to resolve all heterozygous combinations of the HLA-DRB1*03, *08,
      *11, *12, *13 and *14 allele group in a one-step generic HLA-DRB1 typing system.
      Therefore, it is common to employ a secondary technique utilizing group-specific
      primers to amplify this group of alleles separately from the other HLA-DRB1, 
      DRB3, -DRB4 and -DRB5 alleles. This paper describes a polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP) method for broad typing of
      the HLA-DRB1*03, *08, *11, *12, *13 and *14 alleles which, as well as being time
      efficient and cost-effective, has so far allowed the detection of 10 new alleles.
      The new alleles were identified after following up unusual or novel PCR-RFLP
      patterns. Of the 10 novel alleles found so far with this method, seven have been
      described previously while three, DRB1*13022, DRB1*1336 and DRB1*1435, are
      presented here.

PMID- 11532020
TI  - Polymorphism in the promoter region of the gene encoding human allograft
      inflammatory factor-1.
AB  - We have identified a new single nucleotide polymorphism within the promoter
      region of the human allograft inflammatory factor (AIF-1) gene. The polymorphism,
      defined by Genbank accession number AF097515, was characterized as a C/T single
      base pair substitution at position -932. The T allele is associated with both HLA
      DR2 and HLA-B7. Also, this allele creates the consensus binding site for the E
      box that has high affinity for the basic helix-loop-helix (bHLH) family of
      transcription factors.

PMID- 11532021
TI  - Lymphocyte antigens in sheep: linkage to the MHC class II DRB1 gene.
AB  - In this work a typing battery of sera was developed to test lymphocyte antigens
      in sheep. Eight antigens were detected in a Latxa sheep sample. The serological
      determination of these antigens is described. As some of the detected antigens
      segregated in close linkage with class II DRB1 SSCP patterns in two half-sib
      families, we can conclude that they are coded by genes located in the MHC. Gene
      frequencies were very similar in Latxa Mutur Gorria and Latxa Mutur Beltza, the
      two varieties of the Latxa breed. Although few animals were typed in the
      comparison with other typing sera, it seems that two of our sera clusters detect
      the same antigens as those detected by other research groups working in other
      breeds with their own typing batteries.

PMID- 11532022
TI  - HLA-DRB1, -DQA1, -DQB1 and DPB1 susceptibility alleles in Cameroonian type 1
      diabetes patients and controls.
AB  - It is known that certain combinations of alleles within the human leucocyte
      antigen (HLA) complex are associated with susceptibility or resistance to type 1
      diabetes. Variable associations of DR and DQ with type 1 diabetes are documented
      in Caucasians but rarely in African populations; however, the role of HLA-DP
      genes in type 1 diabetes remains uncertain. In order to investigate the HLA class
      II associations with type 1 diabetes in Cameroonians, we used sequence-specific
      oligonucleotide probing (SSOP) to identify DRB1, DQA1, DQB1 and DPB1 alleles in
      10 unrelated C-peptide negative patients with type 1 diabetes and 90 controls
      from a homogeneous population of rural Cameroon. We found a significantly higher
      frequency of the alleles DRB1*03 (chi2 = 17.9; P = 0.001), DRB1*1301 (chi2 =
      37.4; P < 0.0001), DQA1*0301 (chi2 = 18.5; P = 0.001) and DQB1*0201 (chi2 = 37.4;
      P < 0.001) in diabetes patients compared to the control group. The most frequent
      alleles in the control population were DQA1*01, DQB1*0602 and DRB1*15. The
      DRB1*04 allele was not significantly associated with type I diabetes in our study
      population. We observed no significant difference between patients and controls
      in DPB1 allele frequency. In conclusion, the data in Cameroonian diabetes
      patients suggest the existence of HLA class II predisposing and specific
      protective markers, but do not support previous reports of a primary association
      between HLA-DP polymorphism and development of type I diabetes.

PMID- 11532023
TI  - Nomenclature for factors of the HLA System, update February 2001.

PMID- 11532024
TI  - Nomenclature for factors of the HLA System, update March 2001.

PMID- 11532025
TI  - A decade of site- and phosphorylation state-specific antibodies: recent advances
      in studies of spatiotemporal protein phosphorylation.
AB  - From 1990 to 2001, numerous site- and phosphorylation state-specific antibodies
      have been developed and many are now commercially available. These antibodies
      have facilitated understanding of the cytoskeletal organization, signal
      transduction and transcriptional mechanisms as well as clinical diseases. This
      review is an attempt to cover all these aspects.

PMID- 11532026
TI  - Expression of ribosome modulation factor (RMF) in Escherichia coli requires
      ppGpp.
AB  - BACKGROUND: During the transition from the logarithmic to the stationary phase,
      70S ribosomes are dimerized into the 100S form, which has no translational
      activity. Ribosome Modulation Factor (RMF) is induced during the stationary phase
      and binds to the 50S ribosomal subunit, which directs the dimerization of 70S
      ribosomes. Unlike many other genes induced in the stationary phase, rmf
      transcription is independent of the sigma S. To identify the factors that
      regulate the growth phase-dependent induction of rmf, mutant strains deficient in
      global regulators were examined for lacZ expression directed by the rmf promoter.
      RESULTS: Among mutants of defective global regulators, only ppGpp deficiency
      (relA-spoT double mutant) drastically reduced the level of rmf transcription to
      less than 10% of that seen in the wild-type. Neither RMF nor 100S ribosomes were
      detected in this mutant in the stationary phase. rmf transcription correlated
      well with cellular ppGpp levels during amino acid starvation, IPTG induction of
      Ptrc-relA455 and in other mutants with artificially increased ppGpp levels.
      Although the growth rate also correlated inversely with both ppGpp levels and rmf
      transcription, the observation that the growth rates of the ppGpp-deficient and
      wild-type strains varied equivalently when grown on different media indicates
      that the link between rmf transcription and ppGpp levels is not a function of the
      growth rate. CONCLUSIONS: ppGpp appears to positively regulate rmf transcription,
      at least in vivo. Thus, RMF provides a novel negative translational control by
      facilitating the formation of inactive ribosome dimers (100S) under the stringent
      circumstances of the stationary phase.

PMID- 11532027
TI  - Pathways for repair of topoisomerase I covalent complexes in Saccharomyces
      cerevisiae.
AB  - BACKGROUND: The covalent linkage between DNA and the active site tyrosine of
      topoisomerase I can be stabilized by chemotherapeutic agents, adjacent DNA
      lesions, or mutational defects in the topoisomerase itself. Following collision
      with a replication fork, the covalent complex can be converted to a double-strand
      break. Tdp1, an enzyme that can hydrolyse the bond between topoisomerase I and
      DNA, is thought to be involved in the repair of these lesions, but little is
      known about how such repair is accomplished. RESULTS: Reaction kinetics with
      model substrates reveal that the catalytic efficiency of Saccharomyces cerevisiae
      Tdp1 is relatively poor when the scissile bond is located in the middle of a
      duplex, but much better when it is located at the end of a structure. Survival of
      yeast after induction of a toxic topoisomerase is substantially reduced by
      inactivation of the TDP1 gene. Comparison of survival of single and double
      mutants places TDP1 and RAD52 in the same epistasis group but TDP1 and RAD9 in
      different epistasis groups. In the absence of RAD9, inactivation of TDP1 has a
      significant effect on the survival of cells following exposure to camptothecin
      but is without consequence for the survival of agents that do not target
      topoisomerase I. CONCLUSIONS: Tdp1 acts as a specific repair enzyme for
      topoisomerase I lesions. Rather than working at their earliest occurrence, the
      enzyme acts after covalent complexes have been converted to DSBs. A second repair
      pathway also exists that functions independently of Tdp1 but requires RAD9
      function to efficiently repair topoisomerase I-linked DSBs. The efficiency of
      these pathways differs for complexes induced with the chemotherapeutic agent
      camptothecin vs. those accumulated by mutant forms of topoisomerase I.

PMID- 11532028
TI  - Complex phenotype of mice homozygous for a null mutation in the Sp4 transcription
      factor gene.
AB  - BACKGROUND: Sp4 is a zinc finger transcription factor which is closely related to
      Sp1 and Sp3. All three proteins recognize the same DNA elements and can act as
      transcriptional activators through glutamine-rich activation domains. Unlike Sp1
      and Sp3, which are ubiquitous proteins, Sp4 is highly abundant in the central
      nervous system, but also detectable in many other tissues. RESULTS: We have
      disrupted the mouse Sp4 gene by a targeted deletion of the exons encoding the N
      terminal activation domains. Sp4 knockout mice show a complete absence of Sp4
      expression. They develop until birth without obvious abnormalities. After birth,
      two-thirds die within 4 weeks. Surviving mice are growth retarded. Male Sp4null
      mice do not breed. The cause for the breeding defect remains obscure since they
      show complete spermatogenesis. In addition, pheromone receptor genes in the
      vomeronasal organ appear unaffected. Female Sp4null mice have a smaller thymus,
      spleen and uterus. In addition, they exhibit a pronounced delay in sexual
      maturation. CONCLUSIONS: The phenotype of the Sp4null mice differs significantly
      from those described for Sp1-/- and Sp3-/- mice. Thus, the structural
      similarities, the common recognition motif and the overlapping expression pattern
      of these three transcription factors do not reflect similar physiological
      functions.

PMID- 11532029
TI  - Functional interactions of an archaeal sliding clamp with mammalian clamp loader
      and DNA polymerase delta.
AB  - BACKGROUND: By the total genome sequencing of several archaeal organisms, it has
      been confirmed that many archaeal proteins related to genetic information
      systems, including DNA replication, transcription and translation, have similar
      sequences to those of eukaryotes. In eukaryotic DNA replication, proliferating
      cell nuclear antigen (PCNA) works in clamping DNA polymerases on the DNA template
      and accomplishes a processive DNA synthesis. Archaea encode PCNA homologues in
      their genomes and Pyrococcus furiosus PCNA (PfuPCNA) stimulates the DNA
      synthesizing activities of the DNA polymerases, Pol I and Pol II, in this
      organism. RESULTS: We have demonstrated that PfuPCNA interacts functionally with
      calf thymus DNA polymerase delta (Pol delta) and stimulates its activity.
      Moreover, human replication factor C (RFC) enhances the PfuPCNA-dependent DNA
      synthesis activity of Pol delta, indicating that human RFC works as the clamp
      loader for PfuPCNA. These results showed that the three-dimensional structures of
      archaral PCNA and RFC are actually similar enough to their eukaryotic
      counterparts to allow a molecular substitution between the two biological
      domains, albeit at a lower efficiency. CONCLUSIONS: We found that the archaeal
      molecule interacts functionally with the eukaryotic members in the DNA
      replication process. This finding supports the idea that studies on the DNA
      replication mechanism of archaeal organisms will provide many important clues for
      understanding of the intricate molecular recognition that is inherent to the DNA
      replication machinery in Eukarya.

PMID- 11532030
TI  - Reconstitution of recombinant TFIIH that can mediate activator-dependent
      transcription.
AB  - BACKGROUND: TFIIH is one of the general transcription factors required for
      accurate transcription of protein-coding genes by RNA polymerase II. TFIIH has
      helicase and kinase activities, plays a role in promoter opening and promoter
      escape, and is also implicated in efficient activator-dependent transcription.
      RESULTS: We have established a reconstitution system of recombinant TFIIH using a
      three-virus baculovirus expression system. The recombinant TFIIH was active in
      CTD kinase and DNA helicase assays, and showed both basal and activator-dependent
      transcriptional activities that were indistinguishable from those of HeLa cell
      derived TFIIH. Further analyses using recombinant TFIIH confirmed a critical role
      of TFIIH in activator-dependent transcription. The dose response of TFIIH in
      activator-dependent transcription suggested that mere recruitment of TFIIH is not
      sufficient for transcriptional activation. The sensitivity of activator-dependent
      transcription to nonhydrolysable ATP analogues indicated the importance of the
      enzymatic activities of TFIIH in transcriptional activation. CONCLUSIONS: Our
      results raise a possibility that transcriptional activation by GAL4-VP16 requires
      enzymatic activities. Recombinant TFIIH reconstituted from this baculovirus
      system should be useful for analysis of the mechanisms of activation by GAL4
      VP16.

PMID- 11532031
TI  - PAR-6 regulates aPKC activity in a novel way and mediates cell-cell contact
      induced formation of the epithelial junctional complex.
AB  - BACKGROUND: PAR-6, aPKC and PAR-3 are polarity proteins that co-operate in the
      establishment of cell polarity in Caenorhabditis elegans and Drosophila embryos.
      We have recently shown that mammalian aPKC is required for the formation of the
      epithelia-specific cell-cell junctional structure. We have also revealed that a
      mammalian PAR-6 forms a ternary complex with aPKC and ASIP/PAR-3, and localizes
      at the most apical end of the junctional complex in epithelial cells. RESULTS:
      The ternary complex formation and junctional co-localization of PAR-6 with aPKC
      and ASIP/PAR-3 are observed during the early stage of epithelial cell
      polarization. In addition, over-expression of the PAR-6 mutant with CRIB/PDZ
      domain in MDCK cells disturbs the cell-cell contact-induced junctional
      localization of tight junction proteins, as well as inhibiting TER development.
      Furthermore, the binding of Cdc42:GTP to the CRIB/PDZ domain of PAR-6 enhances
      the kinase activity of PAR-6-bound aPKC. Detailed analyses suggest that the
      binding of PAR-6 to aPKC has the intrinsic potential to activate aPKC, which is
      only released when Cdc42:GTP binds to the CRIB/PDZ domain. CONCLUSION: The
      results indicate the involvement of PAR-6 in the aPKC function which is required
      for the cell-cell adhesion-induced formation of epithelial junctional structures,
      possibly through the cooperative regulation of aPKC activity with Cdc42.

PMID- 11532032
TI  - Colorectal neoplasia in ulcerative colitis-recent advances.
AB  - It is recognized that ulcerative colitis (UC) predisposes to the development of
      colorectal adenocarcinoma (CRC), and the molecular pathway for this process
      differs from that for sporadic CRCs. However, several important details regarding
      the risk factors for and the molecular changes underlying UC-related colorectal
      carcinogenesis have only come to light lately. First, recent data suggest
      environmental factors related to long-standing inflammation contribute more to
      this increased cancer risk than an inherited susceptibility. Second, molecular
      changes that may represent the first steps in the development of neoplasia are
      being increasingly identified in non-dysplastic, colitic mucosa. Third, there is
      now good evidence suggesting that UC-related CRC may develop along more than one
      molecular pathway. These emerging data will hopefully contribute to attempts to
      prevent the development of UC-related CRC, e.g. through refining surveillance
      programmes. Details of the molecular heterogeneity of UC-related dysplasia and
      CRC may also help develop reliable tools for diagnosing the former and for
      predicting the behaviour of the latter. Finally, there is increasing awareness of
      non-epithelial colorectal malignancies which are associated with UC and may
      potentially increase in incidence with changes in the medical management of this
      inflammatory disease.

PMID- 11532033
TI  - Morphometric assessment of gastric antral atrophy: comparison with visual
      evaluation.
AB  - AIMS: As part of a multinational effort to reach a consensus in the definition
      and evaluation of atrophic gastritis, we applied morphometric techniques to 22
      antral biopsy specimens examined visually by 12 experienced gastrointestinal
      pathologists. METHODS AND RESULTS: Atrophy was defined as loss of glands. Each
      pathologist graded atrophy with both non-standardized and standardized
      approaches. Discriminant function analyses of morphometric measurements were
      conducted to validate and grade atrophy. Kappa statistics were used to compare
      the performance of each pathologist against the group mode and against the
      discriminant functions' grading of atrophy. Three morphometric indexes showed
      significant differences among categories of atrophy utilizing non-standardized as
      well as standardized visual atrophy grades: (i) the ratio of glandular length to
      total mucosal thickness; (ii) the proportion of the secretory compartment area
      occupied by glands; and (iii) the number of glandular cross sections per 40x
      microscopic field. The discriminant function analyses verified all cases
      classified visually as either non-atrophic, or moderately/severely atrophic; it
      verified as mildly atrophic 40% of the cases classified visually as mildly
      atrophic; and classified the remaining 60% as moderately or severely atrophic.
      The kappa statistics were good or excellent for the majority of pathologists.
      CONCLUSIONS: The evaluation of antral atrophy, simply defined as loss of glands,
      can be reliable and reproducible. The visual grading of atrophy as absent,
      moderate and severe is entirely consistent with objective morphometric
      observations.

PMID- 11532034
TI  - Melanosis of the appendix: common in the paediatric age group.
AB  - AIMS: To investigate the incidence of melanosis of the vermiform appendix in a
      paediatric population, and look for correlations with season, apoptotic rate and
      inflammation as possible causes. METHODS AND RESULTS: We examined 300 appendices
      removed for abdominal pain and incidentally during other procedures over the
      period January 1996 to March 1999. Melanosis was present in 46% of adequate
      specimens with an even distribution between sexes and age groups. The two older
      age groups had a relatively higher incidence of severe involvement compared with
      the younger age group, although the difference was not statistically significant.
      We attempted to correlate the presence of melanosis with the season of the year
      and the peak incidences of paediatric gastrointestinal disease but could find no
      relationship. No statistically significant correlation was found between
      apoptotic rate and the presence of melanosis. CONCLUSIONS: The findings suggest
      melanosis of the appendix is relatively common. It is probably due to apoptosis
      associated with increased epithelial cell turnover due to many differing causes
      including infection, with purgative ingestion probably involved in only a
      minority of paediatric cases.

PMID- 11532036
TI  - Scoring nuclear pleomorphism in breast cancer.
AB  - AIMS: Nuclear grade has equal weight with mitotic index and acinus formation in
      grading breast cancer, but criteria for its assessment are less well defined.
      This study examines consistency of nuclear grading in breast cancer and whether
      improved nuclear grading criteria are required. METHODS AND RESULTS: Photographic
      prints of haematoxylin-eosin sections of 100 unselected symptomatic breast
      cancers were circulated to histopathologists who assigned each carcinoma a
      nuclear pleomorphism score on a linear analogue scale 0-100 (0-33 equating to
      nuclear pleomorphism grade 1, 34-66 to grade 2, and 67-100 to grade 3). Seventeen
      histopathologists completed the exercise, including 11 breast specialists. While
      kappa scores for the implied nuclear grades indicated 'moderate' or 'good'
      agreement between individuals and the group as a whole, seven pathologists
      allocated analogue scores significantly lower than the median score allocated by
      the group to each case, while five allocated significantly higher scores. The
      range was from analogue scores 11.3 units lower on average than the median
      (assigning 27% of carcinomas nuclear grade 1, 60% grade 2, and 13% grade 3) to
      scores 7.5 units higher on average than the median (assigning only 2% carcinomas
      nuclear grade 1, 46% grade 2, and 52% grade 3). Five of six non-specialists
      allocated scores significantly lower than the group medians but only two of 11
      specialists did so (P=0.018). CONCLUSIONS: Systematic differences between
      pathologists in scoring nuclear pleomorphism in breast cancer potentially
      contribute to differences in allocating overall grade and confirm the need for
      improved nuclear grading criteria. Specialists tend to allocate higher
      pleomorphism scores than non-specialists.

PMID- 11532035
TI  - MLH1 and MSH2 protein immunohistochemistry is useful for detection of hereditary
      non-polyposis colorectal cancer in young patients.
AB  - AIMS: Hereditary non-polyposis colorectal cancer is related to germline mutations
      of DNA mismatch repair genes MLH1 and MSH2, which result in microsatellite
      instability and loss of protein expression of the corresponding mutated gene in
      the tumour tissue. METHODS AND RESULTS: MLH1 and MSH2 protein expression was
      studied by immunohistochemistry in paraffin-embedded surgical samples of 100
      colorectal adenocarcinomas occurring before 50 years of age. Absence of tumour
      cell nuclear staining with positive internal control (normal mucosa, lymphoid
      follicles) was considered negative. Loss of MLH1 or MSH2 expression was found in
      20 cases with microsatellite instability in 15 cases. Twelve of these patients
      had a family history of colorectal cancer. Compared with MLH1- and MSH2-positive
      cases, MLH1- or MSH2-deficient colorectal adenocarcinomas were significantly
      associated on multivariate analysis with a younger age (38 vs. 43 years,
      P;0.0224), a larger tumour size (60 +/- 6 vs. 46 +/- 2 mm, P=0.0291), an
      expanding margin (85% vs. 51%, P=0.0159), a higher number of tumour-infiltrating
      lymphocytes assessed by CD3 immunostaining (202 +/- 48 vs. 33 +/- 4 CD3+
      lymphocytes/10 high-power fields, P=0.0039), and a grade 2 Crohn's like lymphoid
      reaction (70% vs. 9%, P=0.0037). The two groups were not different for tumour
      site, differentiation, pTNM stage, vascular and perineural invasion, peripheral
      adenomatous residue, and 5-year survival rates. CONCLUSIONS: MLH1- or MSH2
      deficient colorectal carcinomas of young patients exhibit pathological and
      molecular features similar to hereditary non-polyposis colorectal cancer. This
      suggests that MLH1 and MSH2 immunohistochemistry is valuable for detecting
      hereditary non-polyposis colorectal cancer in young patients.

PMID- 11532037
TI  - Distribution of alpha glutathione S-transferase in ovarian neoplasms: an
      immunohistochemical study.
AB  - AIMS: Alpha glutathione S-transferase (alpha-GST) has been shown to be an
      immunohistochemical marker for delta(4-5) isomerase, an enzyme active in
      steroidogenesis. The purpose of this study was to document the distribution of
      alpha-GST in ovarian neoplasms in order to evaluate its usefulness as a
      diagnostic tool. METHODS AND RESULTS: A total of 92 tumours (25 sex cord/stromal,
      53 epithelial and 14 germ cell) were subjected to immunohistochemistry using a
      commercially available polyclonal antibody to alpha-GST. The avidin-biotin
      complex was used as a detection system. Positive staining was found in luteinized
      stromal cells of all tumour types (58/92). This included the Leydig cells of
      Sertoli-Leydig cell tumours (7/7) and was particularly prominent in the stromal
      cells of both benign and malignant mucinous tumours (24/25). Granulosa and
      Sertoli cells showed weak or no intracytoplasmic staining, which is expected
      because they do not normally produce androstenedione. They did show some
      intranuclear staining. Malignant mucinous (12/25) and occasional other epithelial
      tumours showed focal intracytoplasmic positive staining. Yolk sac tumours showed
      focal positivity (7/8). CONCLUSIONS: Intracytoplasmic staining of stromal cells
      is considered to indicate steroidogenesis and intranuclear staining the
      intracytoplasmic transport function of alpha-GST. The intracytoplasmic staining
      of mucinous carcinomas might represent an up-regulation of some detoxification
      function. The findings suggest that antibody to alpha-GST has some value in the
      investigation of ovarian pathology and could readily be included in any panel of
      antibodies used to investigate ovarian neoplasms of uncertain histogenesis.

PMID- 11532038
TI  - CD10 is a sensitive and diagnostically useful immunohistochemical marker of
      normal endometrial stroma and of endometrial stromal neoplasms.
AB  - AIMS: The CD10 antigen is expressed in acute lymphoblastic leukaemia and follicle
      centre cell lymphoma. A recent study investigating the expression of CD10 in a
      wide range of non-haematopoietic neoplasms found positive staining in a small
      number of endometrial stromal sarcomas as well as in normal endometrial stroma.
      The present study aimed to ascertain whether CD10 positivity is indeed found in
      normal endometrial stroma and endometrial stromal neoplasms. Staining of a range
      of tumours which can be confused morphologically with endometrial stromal
      neoplasms was also undertaken to ascertain whether antibodies against CD10 are of
      value in a diagnostic sense. METHODS AND RESULTS: Neoplasms included in the study
      were endometrial stromal nodule (n=1), low-grade endometrial stromal sarcoma
      (ESS) (n=13), high-grade ESS (n=6), mixed endometrial stromal-smooth muscle
      tumour (n=1), uterine cellular leiomyoma (n=10), uterine leiomyosarcoma (n=5),
      adult granulosa cell tumour (AGCT) (n=10), undifferentiated endometrial carcinoma
      (n=6), uterine carcinosarcoma with an endometrial stromal component (n=1) and
      type II uterine mesenchymal tumour with sex cord-like elements (n=1). Cases of
      proliferative (n=5), secretory (n=5) and atrophic (n=3) endometrium were also
      stained. There was positive staining of stroma but not of glands in all cases of
      non-tumorous endometrium. There was positive staining of the endometrial stromal
      nodule and of all low-grade ESS. Staining in these varied but was often diffuse
      and of moderate to strong intensity. There was positive staining of four of six
      high-grade ESS, but this was usually focal. There was also positive staining of
      the endometrial stromal component in the mixed endometrial stromal-smooth muscle
      tumour and in the uterine carcinosarcoma. Most cellular leiomyomas were
      completely negative although three exhibited weak positivity. There was some
      positivity, usually focal or weak, of three of five leiomyosarcomas. Most AGCT
      and undifferentiated carcinomas were completely negative although one case of
      each exhibited focal staining. There was focal staining of the type II uterine
      mesenchymal tumour with sex cord-like elements. CONCLUSION: CD10 is a reliable
      and sensitive immunohistochemical marker of normal endometrial stroma.
      Positivity, which is often strong and/or diffuse is found in endometrial stromal
      nodules and low-grade ESS. Positive staining with CD10, when strong and diffuse,
      may be useful in distinguishing these tumours from histological mimics,
      especially cellular leiomyoma and AGCT which are generally negative. In this
      situation, CD10 should be used as part of a panel which might include desmin and
      alpha-inhibin depending on the differential diagnosis considered. Positive
      staining with CD10 in a high-grade uterine sarcoma which is negative with muscle
      markers might indicate endometrial stromal differentiation and identify a group
      of neoplasms which it is correct to diagnose as high-grade ESS rather than
      undifferentiated uterine sarcoma.

PMID- 11532039
TI  - Primary squamous cell carcinoma of the thyroid gland: an entity with aggressive
      clinical behaviour and distinctive cytokeratin expression profiles.
AB  - AIMS: Primary squamous cell carcinoma of the thyroid gland is uncommon. This
      study aims to identify the clinicopathological features and the pattern of
      expression of cytokeratins and oncoproteins in this tumour. METHODS AND RESULTS:
      Histological slides from Chinese patients with thyroid cancer treated in our
      institution from 1980 to 1999 were reviewed. Patients with primary squamous cell
      carcinoma of the thyroid were identified and their clinical records were
      analysed. The expression of cytokeratins (CKs), p53 and p21 in these cases were
      also studied by an immunohistochemical method. Four women (mean age 71 years)
      with squamous cell carcinoma of thyroid were found. The main presenting features
      were signs and symptoms of airway obstruction in three patients and neck swelling
      in one. The tumours were located at the right lobe (n=2), left lobe (n=1) or in
      both lobes of the thyroid (n=1). One patient died shortly after admission and the
      other three died within 4 months after thyroidectomy. The p53 protein was
      positive in 50% (2/4) of the tumours and p53+ tumours were poorly differentiated.
      The tumours were negative for p21. CK19 was expressed in all the tumours while
      CK7 expression was noted in 3/4 of the tumours. One carcinoma showed focal
      positivity to CK18. The tumours were negative for CKs 1, 4, 6, 10/13 and 20. The
      pattern of cytokeratin expression in squamous cell carcinoma of the thyroid gland
      was different from carcinoma showing thymus-like differentiation (CASTLE) of the
      thyroid gland and oesophageal squamous cell carcinoma. CONCLUSIONS: Squamous cell
      carcinoma of the thyroid has aggressive clinical behaviour and characteristic CK
      expression pattern. p53 over-expression in these tumours was associated with
      tumour differentiation.

PMID- 11532040
TI  - Cellular myxoma of soft tissue: a clinicopathological study of 38 cases
      confirming indolent clinical behaviour.
AB  - AIMS: To characterize the clinicopathological features and biological potential
      of a group of soft tissue lesions with morphology intermediate between
      intramuscular myxoma and low-grade myxofibrosarcoma. METHODS AND RESULTS: Thirty
      eight lesions in 37 patients were retrieved from the authors' consultation files.
      Clinical and follow-up data were obtained and the lesions were also studied
      immunohistochemically. Tumours occurred in adults aged 25-83 years (mean 51.9
      years) with a slight predominance in females. All cases, except two, were
      solitary. The extremities were preferentially involved (18 lower limb; nine upper
      limb), with seven lesions arising around the upper (2/7) and lower limb (5/7)
      girdles and four lesions occurring at other locations. Twenty-nine of 31 of the
      tumours, for which the depth was known, were situated deep to the superficial
      fascia, although only 19 were strictly intramuscular. Histologically these
      lesions were both more cellular and more vascular than intramuscular myxoma,
      while lacking the cytological pleomorphism, nuclear atypia and curvilinear
      vascular pattern characteristic of low-grade myxofibrosarcoma. CD34 positivity in
      lesional cells was identified in 17/30 (57%) cases, probably reflecting their
      fibroblastic nature. Staining for alpha-smooth muscle actin was focally positive
      in 3/30 (10%) cases, while desmin and S100 protein staining were consistently
      negative. Clinical follow-up data (available in 22 cases; median duration 30
      months) demonstrate that these lesions behave in a benign fashion with only a
      small risk of local recurrence if not excised completely; in this study only two
      tumours recurred, both of which originally had been incompletely excised. None
      metastasized. CONCLUSIONS: The risk of recurrence in this group of lesions which
      we have designated 'cellular myxoma' appears to be low. Consequently simple
      complete local excision is most often adequate treatment. Longer follow-up (5-10
      years or more) in a larger number of cases will be important in more definitively
      confirming the natural history of these lesions.

PMID- 11532041
TI  - Diverse differentiation in malignant peripheral nerve sheath tumours associated
      with neurofibromatosis-1: an immunohistochemical and ultrastructural study.
AB  - AIMS: The diverse histological features in malignant peripheral nerve sheath
      tumours (MPNSTs) associated with NF-1 were investigated by immunohistochemical
      and electron microscopic analysis. Our study is focused on the differentiation of
      the tumour cells in the heterogeneous components. METHODS AND RESULTS: Twenty
      three cases were classified as conventional type, epithelioid type, anaplastic
      type, and heterogeneous type, and divided into three groups by the presence of
      S100 protein (S100)-positive cells in each tumour; Group A was defined as having
      >50% S100+ cells, Group B as having <50%, and Group C as cases with no positive
      cells. To investigate the differentiation of the tumour cells, the morphology and
      immunoreactivity for neural or mesenchymal markers among the three groups were
      compared. For the identification of Schwannian, perineurial, and endoneurial
      differentiation, markers for S100, EMA and CD34 were used, respectively. In three
      tumours of the Group A type, there were no cases showing differentiation towards
      perineurial or endoneurial cells, or formation of heterogeneous components. In
      nine tumours of the Group B type, one tumour expressed EMA and CD34, suggesting
      probable perineurial and/or endoneurial differentiation. One tumour showed
      rhabdomyoblastic differentiation. Three tumours showed cartilaginous or
      osteogenic differentiation, and one of the three also showed a focal vascular
      differentiation. The surrounding areas of the heterogeneous components were
      composed of mixed S100+ cells and S100- cells. S100- cells in the areas were
      positive for CD34 in one case. In 11 tumours of Group C type, one tumour
      expressed EMA and CD34 suggesting perineurial and/or endoneurial cell
      differentiation. Three tumours showed rhabdomyoblastic differentiation. The
      tumour cells around the heterogeneous components in the three cases were negative
      for EMA and CD34. CONCLUSION: Our results suggest that tumour cells
      differentiating to Schwann cells are not the only component of MPNSTs.
      Furthermore, tumour cells other than Schwann cells are largely related to the
      formation of the heterogeneous components in MPNSTs associated with NF-1.

PMID- 11532042
TI  - Plurihormonal pituitary adenomas: immunostaining of all pituitary hormones is
      mandatory for correct classification.
AB  - AIMS: We studied the clinicopathological characteristics of plurihormonal
      pituitary adenomas. METHODS AND RESULTS: The study material included 167
      plurihormonal adenomas, which consisted of 31% of the surgically removed
      pituitary adenomas that we collected during a 12-year period. The mean age of
      patients with plurihormonal adenoma was 45.7 years (range 13-75 years). There
      were 86 men and 81 women. All tumours were fully classified by
      immunohistochemical staining for seven pituitary hormones or subunits. Thirty
      immunohistochemical subtypes of plurihormonal adenomas were recognized. Hormonal
      symptoms were present in 70% of patients, while serum hormonal levels were
      increased in 89% of patients. Most patients had symptoms related to only one of
      the hormones and only 7% of patients had symptoms related to two hormones. The
      most common hormonal symptom was acromegaly (50%); symptoms related to
      hyperprolactinaemia ranked second (20%). Double immunostaining of all the
      possible combinations of the hormones was performed in 30 selected tumours, and
      they all showed mixtures of hormones in individual adenoma cells in any hormonal
      combinations studied. The latter finding supported the view that plurihormonal
      adenomas are monomorphous adenomas. CONCLUSIONS: Plurihormonal adenomas are
      common pituitary adenomas. Immunohistochemical staining of all pituitary hormones
      is mandatory for correct classification.

PMID- 11532043
TI  - The diagnosis of hydatidiform mole in early tubal ectopic pregnancy.

PMID- 11532044
TI  - Massive haemosiderosis in Wilson's disease.

PMID- 11532045
TI  - Creating digital images of pathology specimens by using a flatbed scanner.

PMID- 11532046
TI  - Proposed technique for sectioning of mastectomy specimens and submission of
      tissue for microscopic examination of breast carcinoma.

PMID- 11532047
TI  - Echocardiography in congenital heart disease: diagnosis, misdiagnosis, and
      ownership.

PMID- 11532048
TI  - Paediatric palliative care: distinctive needs and emerging issues.
AB  - Palliative medicine has developed as a specialized field of practice in recent
      decades but the focus has been very much on older adults with incurable
      malignancies. The needs of dying children have not been addressed adequately and
      the question of who is best placed to provide care to this group remains the
      subject of some contention. Although the principles of palliative care apply
      equally to children, a number of fundamental differences influence their
      application in the paediatric setting. These include a heterogeneous patient
      population, physiological factors, developmental issues, parental involvement in
      care giving and decision making and the desire of most paediatricians to maintain
      close involvement with their patients. Families generally prefer home care and
      even quite severe symptoms can be managed in this environment with appropriate
      planning, expertise and support. The delivery of effective palliative care in the
      paediatric setting is contingent upon overcoming barriers between hospital and
      community and sharing expertise between paediatricians and palliative care
      physicians. Research is also required to increase the evidence base for practice.

PMID- 11532049
TI  - Childhood infections in the tropical north of Australia.
AB  - In the tropical north of Australia there are high rates of infections in
      Aboriginal children living in remote communities. In addition to the burden of
      respiratory infections, diarrhoeal disease and skin sepsis, there are high rates
      of acute rheumatic fever, outbreaks of poststreptococcal glomerulonephritis and
      gonococcal conjunctivitis, endemic trachoma and various intestinal parasites. A
      number of infections generally restricted to the tropics are also present and can
      cause disease in both indigenous and non-indigenous children. These include
      melioidosis, Murray Valley encephalitis and dengue on the east coast. With global
      warming, these infections may become more common and more widespread within
      Australia and the potential for establishment of introduced infections such as
      Japanese encephalitis and malaria may increase.

PMID- 11532050
TI  - Diagnostic accuracy of paediatric echocardiograms interpreted by individuals
      other than paediatric cardiologists.
AB  - OBJECTIVE: To assess the diagnostic error rate among echocardiograms undertaken
      by individuals other than paediatric cardiologists in our referral area.
      METHODOLOGY: External group: The charts and echocardiographic results of all
      patients who had undergone outside echocardiograms between January 1996 and
      December 1999 were reviewed (110). Age at echocardiography, diagnostic
      complexity, presence of any diagnostic errors and the severity of any diagnostic
      errors were identified. Internal group: To assess our own error rate, the initial
      echocardiographic diagnoses of 100 patients undergoing cardiac catheterisation or
      corrective surgery were compared with the post-catheterisation or postoperative
      diagnoses. Age and diagnostic complexity were also assessed in the control group.
      RESULTS: Diagnostic errors occurred in 47/110 patients (44%) of the externally
      studied group (of which 24% were either major or life threatening) as opposed to
      3/100 of the internally studied group, despite the internally studied group being
      of increased diagnostic complexity. Errors were more common and of increased
      severity in infants less than 1 month of age but extended throughout all age
      groups. Major and life threatening errors increased with increasing diagnostic
      complexity. In the externally studied group, 8/47 errors were patients
      inappropriately designated as normal. Four of these patients required cardiac
      surgery or interventional cardiac catheterisation. CONCLUSIONS: This study
      suggests an unacceptably high error rate in paediatric echocardiographic
      diagnoses by non-paediatric cardiologists throughout all age groups. Such errors
      are more likely in younger infants and with increasing diagnostic complexity.

PMID- 11532051
TI  - Paediatric melioidosis in the Northern Territory of Australia: an expanding
      clinical spectrum.
AB  - OBJECTIVE: The objective of this study was to present the laboratory and clinical
      features of the six cases of paediatric melioidosis diagnosed from 1997-2000.
      METHODOLOGY: All cases of melioidosis confirmed by the pathology department of
      Royal Darwin Hospital were prospectively identified by culture and/or serology.
      RESULTS: Four children were Aboriginal and all six cases presented during the
      rainy season (November-April) in rural areas in the tropical Top End of the
      Northern Territory. Delay in diagnosis ranged from 5 and 11 days. Two cases had
      localized melioidosis, two cases had underlying disease and were likely to be
      colonized with Burkholderia pseudomallei (B. pseudomallei). Two cases had
      neurological melioidosis with major residual disability. No deaths occurred.
      CONCLUSIONS: Melioidosis remains an unusual disease in children in the tropical
      Northern Territory. The average annual incidence since 1997 is 5.48 per 100 000.
      This series demonstrates that children in Australia can have serious neurological
      complications from B. pseudomallei infection. All children living in or visiting
      tropical Australia are at risk, especially those residing in rural areas in the
      rainy season. Melioidosis remains a difficult disease to manage, and expert
      opinion should be sought if B. pseudomallei is cultured from any site.

PMID- 11532052
TI  - Glycopeptide prescribing in an Australian tertiary paediatric hospital.
AB  - OBJECTIVE: To assess the extent and appropriateness of glycopeptide use in a
      tertiary Australian Paediatric hospital. METHODOLOGY: A retrospective analysis of
      prescriptions during a six-month period between July 1999 and January 2000.
      Medical records were examined and prescribing practices compared with the
      recommendations of the Hospital Infectious Control Practices Advisory Committee
      (HICPAC) and the Infectious Diseases Society of America (IDSA). RESULTS: Fifty
      one patients were identified who received a total of 98 glycopeptide
      prescriptions. The Haematology/ Oncology unit prescribed 71/98 (72.4%). 68/98
      (69.4%) patients received vancomycin, 9/98 (9.2%) received teicoplanin and 21/98
      (21.4%) a combination of both. 81/98 (82.7%) had central venous catheters and
      69/98 (70.4%) were immunocompromised. 48/98 (49%) prescriptions were for empiric
      treatment with 38/98 (38.8%) for prophylaxis and 11/98 (12.2%) therapeutic. 19/98
      (19.4%) prescriptions were deemed appropriate, 6 (6.1%) by HICPAC criteria, and a
      further 13 (13.3%) by IDSA or other criteria. Of 19 prescriptions started
      appropriately, only 7/17 (41.1%) were continued appropriately beyond 48 h.
      Appropriate cultures were taken before prescription in 93.3% of cases. Dose was
      appropriate in 91/98 (92.9%) and frequency appropriate in all cases. The cost of
      inappropriate prescribing was approximately $9500. DISCUSSION: A high rate of
      inappropriate glycopeptide prescribing was evident in this paediatric population.
      Inappropriate prescribing existed across all subspecialties. Use was primarily
      for empiric therapy and prophylaxis in young children with an oncology diagnosis.
      A number of situations existed where glycopeptide prescription was felt
      appropriate despite not being included in HICPAC/IDSA guidelines. Areas with high
      rates of inappropriate prescribing were identified and will be targeted for
      education and intervention. Audit of practice continues.

PMID- 11532053
TI  - The child of uncertain sex: 17 years of experience.
AB  - OBJECTIVE: To review the common clinical presentations, investigations and final
      diagnosis of children presenting with genital ambiguity. METHODOLOGY:
      Retrospective search of the Royal Children's Hospital, Brisbane, Australia,
      medical records and personal medical database of one of the authors (MJT) between
      1982 and 1999. RESULTS: Fifty-one children aged 0.1-14 (mean 3.9) years were
      identified. Twenty-two cases had a 46XX karyotype, and commonly presented with an
      enlarged phallus (77.2%), urogenital sinus (63.6%) and labioscrotal fold(s)
      (40.9%). Congenital adrenal hyperplasia (CAH) was the most common final diagnosis
      (72.7%). Twenty-nine cases of genital ambiguity had a 46XY karyotype and commonly
      presented with palpable gonad(s) (75.8%), undescended testes (51.7%), penoscrotal
      hypospadias (51.7%) and a small phallus (41.3%). Androgen insensitivity and
      gonadal dysgenesis were the commonest final diagnosis both occurring at a
      frequency of 17.2%. CONCLUSIONS: The results emphasize the importance of CAH as
      the most common diagnosis in 46XX cases presenting with ambiguous genitalia.
      Those with 46XY had a wider range of diagnoses. Despite thorough investigation,
      23.5% had no definite final diagnosis made.

PMID- 11532054
TI  - Effect of recombinant human erythropoietin on transfusion needs in preterm
      infants.
AB  - OBJECTIVE: To study the efficacy, safety and cost effectiveness of recombinant
      human erythropoietin (r-HuEPO) in reducing erythrocyte transfusion needs in very
      low birthweight (VLBW) infants. METHODS: We conducted a non-blind randomized
      controlled trial and assigned 100 VLBW infants, less than 33 weeks gestation, to
      receive either r-HuEPO 750 U/kg per week subcutaneously from day 5 to day 40 or
      no erythropoietin (EPO). Infants received oral iron 3-6 mg/kg per day from day
      10. Transfusion needs were analysed for all enrolled infants and in five weight
      subgroups: birthweight of less than 600 g, 600-799 g, 800-999 g, 1000-1199 g and
      infants more than 1200 g. RESULTS: VLBW infants on r-HuEPO attained higher
      reticulocyte counts and haematocrit than control infants but the mean number of
      transfusions and volume of erythrocyte transfused per infant were not
      statistically different. Of infants 800-999 g at birth, the mean number of
      transfusions per infant was 2.1 compared with 3.5 transfusions per control infant
      (P = 0.04). Volume of erythrocytes transfused was 34.9 +/- 32.1 mL/kg in r-HuEPO
      treated infants and 56.6 +/- 25.8 mL/kg in control infants (P = 0.03). The cost
      per patient for transfusion and EPO was S$388 for r-HuEPO recipient and S$438 for
      control infant. Blood pressure, neutrophil count, platelet count and
      complications of prematurity were not significantly different in both groups of
      VLBW infants. CONCLUSION: r-HuEPO at 750 U/kg per week stimulates erythropoiesis
      in VLBW infants but significantly reduces the need for erythrocyte transfusion
      only in infants weighing 800-999 g at birth.

PMID- 11532055
TI  - Transient hyperphosphatasaemia: an important condition to recognize.
AB  - OBJECTIVE: To investigate the prevalence and aetiology of transient
      hyperphosphatasaemia (TH) of infancy and childhood in a tertiary referral
      paediatric hospital. METHODOLOGY: Retrospective review of the medical records of
      patients with measured plasma alkaline phosphatase (ALP) activity of over 1000
      U/L. RESULTS: Over a period of 1 year, 68 children with plasma ALP activity of
      over 1000 U/L were identified. The main aetiologies were liver disease (34
      cases), TH (21 cases) and bone disease (11 cases). The mean age of children with
      TH was 1 year and 5 months and there was a male predominance (3:1). The children
      with liver and bone disease were older (mean ages of 6 years, 6 months and 5
      years, 1 month, respectively) and there was no gender difference. The mean plasma
      ALP activity for the children with TH was 3395 U/L, and in those patients in whom
      ALP activity was measured sequentially, mean ALP returned to within normal limits
      after an average of 70 days. There was a seasonal predominance of TH cases, with
      a significant number presenting during the winter, suggesting a viral aetiology.
      The most common clinical presentation of children with TH was gastroenteritis
      (8/21). CONCLUSION: Cases of TH can be clearly identified by considering the age
      of the patient and by excluding other known causes of markedly elevated ALP, in
      particular liver or bone disease. Using these exclusion criteria, the prevalence
      of TH was found to be high. Early recognition of this benign condition may
      prevent misdiagnosis and further unnecessary investigations.

PMID- 11532056
TI  - Predictors of neurodevelopmental outcome of Malaysian very low birthweight
      children at 4 years of age.
AB  - OBJECTIVE: To determine neonatal, early developmental and social risk factors
      that predict the neurocognitive and behavioural outcome of very low birthweight
      (VLBW) preschool children at four years of age. METHODOLOGY: From a cohort of 151
      eligible VLBW survivors born in Kuala Lumpur Maternity Hospital, 116 (76.8%) were
      prospectively followed up from birth till four years. A standardised neurological
      examination was performed at one and four years to determine the presence of
      impairment and cerebral palsy, respectively. Cognitive development was assessed
      using the Mental Scale of the Bayley Scales of Infant Development (MDI) at one
      year and the Weschler Preschool and Primary Scale of Intelligence-Revised (WIPPSI
      R) at four years. Motor coordination was assessed using the Movement Assessment
      Battery for Children (Movement-ABC). Mothers completed the Child Behaviour
      Checklist (CBCL) and Parenting Stress Index (PSI) questionnaires. Logistic and
      multiple regression analyses were used to determine factors associated with
      cerebral palsy, IQ scores, Movement-ABC and CBCL scores. RESULTS: Factors
      associated with cerebral palsy were lower MDI scores at one year (P = 0.001) and
      late neonatal cranial ultrasound abnormalities (P = 0.036). Minor (P = 0.016) or
      major impairment (P = 0.003) at one year of age and a low level of paternal
      education (P = 0.01) were associated with poor motor function on the Movement-ABC
      scale. Lower levels of maternal education (P < 0.001), impairment at one year (P
      = 0.002) and late neonatal cranial ultrasound abnormalities (P = 0.039) predicted
      Full Scale IQ scores. Higher PSI scores (P = 0.001), younger mothers (P = 0.003)
      and late neonatal cranial ultrasound abnormalities (P = 0.009) were associated
      with worsened child behaviour scores on the CBCL scale. CONCLUSION: Social
      factors and the caregiving environment were important determinants of cognitive
      and behavioural outcome. Cranial ultrasound abnormalities in the late neonatal
      period and the developmental status at one year might be useful in identifying
      high risk infants in need of long-term surveillance.

PMID- 11532057
TI  - Risk factors for small-for-gestational-age babies: The Auckland Birthweight
      Collaborative Study.
AB  - OBJECTIVE: This case-control study determined whether internationally recognized
      risk factors for small-for-gestational-age (SGA) term babies were applicable in
      New Zealand. METHODOLOGY: All babies were born at 37 or more completed weeks of
      gestation in one of three hospitals in Auckland. Cases weighed less than the sex
      specific 10th percentile for gestational age at birth, and controls (appropriate
      for-gestational-age (AGA)) were a random selection of heavier babies. Information
      was collected by maternal interview and from obstetric databases. RESULTS:
      Information from 1714 completed interviews (844 SGA and 870 AGA) was available
      for analysis. Computerized obstetric records were available for 1691 of the 1701
      women who consented to such access. In a multivariate analysis allowing for sex,
      gestational age at birth, social class and other potential confounders, mothers
      who smoked had a significantly increased risk of an SGA baby (adjusted OR 2.41;
      95% CI 1.78-3.28), as did primiparous mothers (adjusted OR 1.34; 95% CI 1.03
      1.73), mothers of Indian ethnicity (adjusted OR 3.22; 95% CI 1.95-5.30), women
      with pre-eclamptic toxaemia (adjusted OR 2.42; 95% CI 1.08-5.40) and those with
      pre-existing hypertension toxaemia (adjusted OR 5.49; 95% CI 1.81-16.71). Mothers
      of SGA infants were shorter (P < 0.001) and reported lower prepregnancy body
      weights (P < 0.001) than mothers of AGA infants. The population attributable
      fraction for smoking suggests that up to 18% of SGA infants born in the ABC Study
      could be related to maternal smoking. CONCLUSIONS: Risk factors associated with
      SGA births in other countries are also important in New Zealand. Smoking in
      pregnancy is an important and potentially modifiable behaviour, and efforts to
      decrease the number of women who smoke during pregnancy should be encouraged.

PMID- 11532058
TI  - Determinants of linear growth in Malaysian children with cerebral palsy.
AB  - OBJECTIVE: To compare the linear growth and nutritional parameters of a group of
      Malaysian children with cerebral palsy (CP) against a group of controls, and to
      determine the nutritional, medical and sociodemographic factors associated with
      poor growth in children with CP. METHODOLOGY: The linear growth of 101 children
      with CP and of their healthy controls matched for age, sex and ethnicity was
      measured using upper-arm length (UAL). Nutritional parameters of weight, triceps
      skin-fold thickness and mid-arm circumference were also measured. Total caloric
      intake was assessed using a 24-h recall of a 3-day food intake and calculated as
      a percentage of the Recommended Daily Allowance. Multiple regression analysis was
      used to determine nutritional, medical and sociodemographic factors associated
      with poor growth (using z-scores of UAL) in children with CP. RESULTS: Compared
      with the controls, children with CP had significantly lower mean UAL measurements
      (difference between means -1.1, 95% confidence interval -1.65 to - 0.59), weight
      (difference between means -6.0, 95% CI -7.66 to -4.34), mid-arm circumference
      (difference between means -1.3, 95% CI -2.06 to -0.56) and triceps skin-fold
      thickness (difference between means -2.5, 95% CI -3.5 to -1.43). Factors
      associated with low z-scores of UAL were a lower percentage of median weight (P <
      0.001), tube feeding (P < 0.001) and increasing age (P < 0.001). CONCLUSION: A
      large proportion of Malaysian children with CP have poor nutritional status and
      linear growth. Nutritional assessment and management at an early age might help
      this group of children achieve adequate growth.

PMID- 11532059
TI  - Clinical correlates of response to pneumococcal immunization.
AB  - OBJECTIVE: The inability to form antibodies to polysaccharide antigens may occur
      as a part of a more significant immunodeficiency or as an isolated defect. The
      latter has been reported in some children with recurrent upper and lower
      respiratory tract infections and evaluation of the responsiveness of such
      patients to polysaccharide antigens is indicated as part of their assessment. The
      present study evaluated the pattern of antibody responses of patients immunized
      with pneumococcal vaccine as part of the investigation of recurrent upper and
      lower respiratory tract infections to determine if any correlation exists between
      these responses and clinical presentation. METHODOLOGY: An analysis was performed
      of antibody responses to pneumococcal serotypes 3, 4 and 6 following immunization
      with a 23-valent vaccine in 42 children with normal IgG levels who were evaluated
      for recurrent infections. Antibody responses were assessed in relation to
      clinical features and the results of other immunological investigations. RESULTS:
      Of the 42 patients evaluated, 25 (59%) were responders to all serotypes tested.
      Failure to respond to serotype 3 alone was the least common pattern of non
      response. Recurrent pneumonia, but not otitis media with discharge or chronic
      productive cough, was significantly associated with a lack of response to two or
      three serotypes. Failure to respond to serotype 3 alone or in combination with
      other serotypes was associated with more significant immune abnormalities.
      CONCLUSION: In a selected population of children with recurrent bacterial
      infections, pneumococcal serotype 3 is a strong immunogen. In this clinical group
      recurrent pneumonia is associated with a defect in response to multiple
      pneumococcal serotypes.

PMID- 11532060
TI  - Passive exposure to tobacco smoke and bacterial meningitis in children.
AB  - OBJECTIVE: To determine whether an association exists between passive exposure to
      tobacco smoke and bacterial meningitis in childhood, in an Australian population.
      METHODOLOGY: A retrospective, case-controlled telephone survey of the parents of
      71 children admitted to the Women's and Children's Hospital, North Adelaide, with
      bacterial meningitis between 1990 and 1999. RESULTS: The annual incidence of
      Haemophilus influenzae type b (Hib) meningitis decreased significantly during the
      study period (11.0 cases per year 1991-93 and 1.5 cases per year 1994-99,
      Fisher's exact test; P < 0.001) whilst pneumococcal cases significantly increased
      (2.3 cases per year 1991-93 and 4.9 cases per year 1994-99, Fisher's exact test;
      P < 0.001). Although comparable numbers of cases and controls came from smoking
      families (41% vs 45%), more cases came from bi-parental smoking households (17%
      vs 8%; odds ratio (OR) = 2.20, 95% confidence interval (CI) 0.77-6.24) and cases
      were more likely to live in households where parents smoked inside (27% vs 13%;
      OR 2.51, 95% CI 1.05-6.03). In households where parents smoked, children who had
      had meningitis were significantly more likely to have parents who smoked inside
      the house, than children who had not had meningitis (66% vs 28%, Fisher's exact
      test; P = 0.005). CONCLUSION: This study suggests there may be an association
      between high levels of passive exposure to tobacco smoke and bacterial meningitis
      in Australian children. A study with larger numbers of affected children which
      quantifies passive exposure to tobacco smoke is needed to determine the strength
      of this association.

PMID- 11532061
TI  - 5: comparing proportions using the chi-squared test.

PMID- 11532062
TI  - Teenage coma.

PMID- 11532063
TI  - Leukaemia presenting as respiratory distress in a child with asthma.
AB  - Asthma is the most common reason for children to present to an emergency
      department complaining of shortness of breath. The diagnosis, based on one or
      more of a positive history of atopy, physical examination findings consistent
      with reactive airways disease, and a clinical response to bronchodilator therapy
      is usually straightforward. It is important however, to consider other diagnoses,
      particularly when patients present differently from that which has previously
      been documented and/or have unexplained physical findings.

PMID- 11532064
TI  - Congenital splenic cyst: a case report and review of the literature.
AB  - There are very few cases of antenatally diagnosed congenital splenic cyst
      described in literature. The present case of congenital splenic cyst was first
      suspected on ultrasound examination at 20 weeks of gestation and followed
      subsequently. Its exact location in the spleen was found on postnatal ultrasound
      examination. The aetiology, differential diagnosis, complications and management
      strategies of this lesion are also discussed.

PMID- 11532065
TI  - Pseudo-maple syrup urine disease due to maternal prenatal ingestion of fenugreek.
AB  - Fenugreek, maple syrup and the urine of maple syrup urine disease (MSUD) patients
      all share a characteristic odour originating from a common component, sotolone.
      Ingestion of fenugreek by mothers during labour resulted in a maple syrup-like
      odour in their newborn infants, leading to a false suspicion of MSUD.

PMID- 11532066
TI  - Intracranial venous thrombosis and pulmonary embolism with antiphospholipid
      syndrome in systemic lupus erythematosus.
AB  - The presence of antiphospholipid antibodies is associated with arterial and
      venous thrombosis. A 14-year-old girl, with systemic lupus erythematosus (SLE),
      developed headache and cough and was found to have intracranial venous sinus
      thrombosis with secondary pulmonary embolism associated with antiphospholipid
      syndrome. Clinical and radiological improvement occurred with anticoagulation
      therapy. Because SLE is commonly associated with antiphospholipid antibodies,
      thromboembolic events should be considered in the differential diagnosis of both
      cough and headache in children with SLE.

PMID- 11532067
TI  - Rhabdomyolysis following status asthmaticus.
AB  - A 15-year-old Chinese boy developed rhabdomyolysis with myoglobinuria and marked
      elevation of serum creatine phosphokinase following a prolonged and severe attack
      of asthma. He recovered after vigorous hydration and supportive treatment.
      Clinicians should be aware of this potentially fatal, albeit rare, complication
      of status asthmaticus.

PMID- 11532068
TI  - Acetazolamide poisoning in a toddler.
AB  - Acetazolamide ingestion and its sequelae have not been previously reported in
      children. A 12-month-old girl, weighing 10 kg, developed metabolic acidosis
      following ingestion of between 500 and 1250 mg of acetazolamide. The maximum base
      deficit recorded was 11.6. She was treated with sodium bicarbonate and recovered
      completely. Accidental poisoning should be included in the differential diagnosis
      of a child presenting with metabolic acidosis.

PMID- 11532069
TI  - Somatostatin analogs.
AB  - Somatostatin is a hypothalamic peptide hormone that inhibits the secretion of
      growth hormone, glucagon, insulin, gastrin and secretin, and also plays a role in
      neural transmission. Because of its wide range of possible clinical applications
      hundreds of somatostatin analogs have been synthesized and bioassayed to date.
      This review gives a historical perspective, summarizing approximately 30 years of
      research on somatostatin. The main focus is on the structure-activity
      relationships and conformational studies of the last generation of somatostatin
      agonists and their selectivity for five somatostatin receptor subtypes.
      Achievements in the synthesis of nonpeptide somatostatin analogs, as well as the
      first somatostatin antagonists, are also discussed. Finally, the use of a cyclic
      somatostatin scaffold to design ligands for other G-protein-coupled receptors,
      such as opioid and melanocortin receptors, is mentioned.

PMID- 11532070
TI  - Amphipathic control of the 3(10)-/alpha-helix equilibrium in synthetic peptides.
AB  - A series of short, amphipathic peptides incorporating 80% C(alpha),C(alpha)
      disubstituted glycines has been prepared to investigate amphipathicity as a helix
      stabilizing effect. The peptides were designed to adopt 3(10)- or alpha-helices
      based on amphipathic design of the primary sequence. Characterization by circular
      dichroism spectroscopy in various media (1 : 1 acetonitrile/water; 9 : 1
      acetonitrile/water; 9 : 1 acetonitrile/TFE; 25 mM SDS micelles in water)
      indicates that the peptides selectively adopt their designed conformation in
      micellar environments. We speculate that steric effects from ith and ith + 3
      residues interactions may destabilize the 3(10)-helix in peptides containing
      amino acids with large side-chains, as with 1-aminocyclohexane-1-carboxylic acid
      (Ac(6)c). This problem may be overcome by alternating large and small amino acids
      in the ith and ith + 3 residues, which are staggered in the 3(10)-helix.

PMID- 11532071
TI  - Syntheses, characterization and application of cross-linked polystyrene
      ethyleneglycol acrylate resin (CLPSER) as a novel polymer support for polypeptide
      syntheses.
AB  - Cross-linked polystyrene-ethyleneglycol acrylate resin (CLPSER) was developed for
      the solid-phase synthesis of peptide by introducing a cross-linker, O,O'-bis(2
      acrylamidopropyl)polyethylene glycol(1900) (Acr(2)PEG), into polystyrene. The
      cross-linker was prepared by treating acryloyl chloride with O,O'-bis(2
      aminopropyl) polyethylene glycol(1900) [(NH(2))(2)PEG] in the presence of
      diisopropylethylamine. The copolymer was prepared either by bulk or inverse
      suspension copolymerization of Acr(2)PEG(1900) and styrene using sorbitan
      monolaurate as the suspension stabilizer, and a mixture of ammonium
      peroxodisulfate and benzoyl peroxide as the radical initiators. The resin was
      characterized using gel-phase (13)C NMR, infrared (KBr) spectroscopic techniques
      and the morphological features of the resin were investigated using scanning
      electron microscopy photographs. CLPSER showed excellent swelling in a broad
      range of solvents and was found to be chemically inert to various reagents and
      solvents used in solid-phase peptide synthesis. To demonstrate the usefulness of
      the new resin in polypeptide synthesis, the support was derivatized with an
      'internal reference' amino acid (norleucine) and a handle 4-(4-hydroxymethyl-3
      methoxy)butyric acid. The new resin was compared with commercial supports such as
      Merrifield and Sheppard resins by synthesizing an acyl carrier protein (65-74)
      fragment under the same experimental conditions. HPLC profiles revealed the high
      efficiency of the newly developed support. Resin capability in peptide synthesis
      was further demonstrated by the solid phase synthesis of a 25-residue peptide
      from the E2/NS1 region hepatitis C viral polyprotein.

PMID- 11532072
TI  - The development of highly efficient onium-type peptide coupling reagents based
      upon rational molecular design.
AB  - Novel and highly efficient immonium-, pyridinium- and thiazolium-type peptide
      coupling reagents, such as BOMI, BDMP, BPMP, BEP, FEP, BEPH, FEPH and BEMT, were
      developed by rational modifying of the molecular structures of commonly used
      uronium-type reagents. The high efficiency of these onium salts has been
      evaluated and proven by model reaction tests and the successful synthesis of
      various oligopeptides and biologically active peptides, both in solution and in
      the solid-phase, for example Leu-enkephalin, the pentapeptide moiety of
      Dolastatin 15 and the immunosuppressive undecapeptide cyclosporin O. Based upon
      these results, the relationship between the molecular structure and the
      capability of onium-type peptide coupling reagents was studied. A preliminary
      guideline for the molecular design of onium-type coupling reagents was developed.

PMID- 11532073
TI  - Novel cyclic peptide inhibits intercellular adhesion molecule-1-mediated cell
      aggregation.
AB  - Leukocyte adherence mediated by intercellular adhesion molecule-1 (ICAM-1)
      binding to leukocyte function-associated antigen (LFA-1) is required for proper
      inflammatory and immune function. Inhibition of ICAM-1?LFA-1 binding using
      monoclonal antibodies (mAb) has been shown to be efficacious at inhibiting
      lymphoma metastasis as well as leukocyte emigration into tissue in a number of
      inflammatory diseases such as ischemia-reperfusion injury, septic shock and
      rheumatoid arthritis. In this report, we describe the development and
      characterization of a small peptide antagonist of ICAM-1-dependent cell
      aggregation. By using repeated selection of a cyclic nonapeptide phage display
      library on purified ICAM-1, we identified phage that were competitively eluted
      with anti-ICAM-1 mAb. The peptide sequences were determined by nucleotide
      sequencing, and the peptide sequence (C*LLRMRSIC*) (IP01) that occurred most
      frequently was chosen for further study. Phage expressing this peptide sequence
      specifically bound ICAM-1 over a range of 5 x 10(6) to 1 x 10(8) phage/microL. A
      cyclic IP01 peptide, linear IP01 peptide, a cyclic nonapeptide with a scrambled
      IP01 sequence, and a random, cyclic nonapeptide were synthesized. The cyclic and
      linear IP01 peptides were able to inhibit ICAM-1-mediated cell aggregation at a
      concentration of 1 mM, whereas the random and scrambled peptide sequences did not
      alter aggregation. Cyclic IP01 had a half-maximal inhibitory concentration of
      approximately 970 microM. Cyclic IP01 did not inhibit cellular aggregation that
      was dependent on ICAM-2 or ICAM-3. Alanine substitutions in the cyclic IP01
      identified at least four amino acids necessary for inhibition of ICAM-1 dependent
      cell aggregation; leucine 2, leucine 3, methionine 5, and arginine 6. Finally, we
      showed that cyclic IP01 can inhibit firm adhesion of neutrophils to endothelium,
      a critical event in inflammatory diseases, in an assay that recapitulates
      physiologic flow conditions. Homology of IP01 with the primary amino acid
      sequences of the alpha or beta subunit of LFA-1 was not identified. Thus, we
      identified a unique molecule that inhibits ICAM-1 dependent cell adhesion, but is
      not related to the primary sequence of the ICAM-1 ligand LFA-1. Due to the small
      size and ability to block cell-cell adhesion, IP01 may serve as a useful tool for
      study of ICAM-1 and LFA-1 biology as well as for the development of small
      molecule therapeutics.

PMID- 11532074
TI  - Development of potent glucagon antagonists: structure-activity relationship study
      of glycine at position 4.
AB  - We examined the functional role of glycine at position 4 in the potent glucagon
      antagonist [desHis(1), Glu(9)]glucagon amide, by substituting the L- and D
      enantiomers of alanine and leucine for Gly(4) in this antagonist. The methyl and
      isobutyl side-chain substituents were introduced to evaluate the preference shown
      by the glucagon receptor, if any, for the orientation of the N-terminal residues.
      The L-amino acids demonstrated only slightly better receptor recognition than the
      D-enantiomers. These results suggest that the Gly(4) residue in glucagon
      antagonists may be exposed to the outside of the receptor. The enhanced binding
      affinities of analogs 1 and 3 compared with the parent antagonist, [desHis(1),
      Glu(9)]glucagon amide, may have resulted from the strengthened hydrophobic patch
      in the N-terminal region and/or the increased propensity for a helical
      conformation due to the replacement of alanine and leucine for glycine. Thus, as
      a result of the increased receptor binding affinities, antagonist activities of
      analogs 1-4 were increased 10-fold compared with the parent antagonist,
      [desHis(1), Glu(9)]glucagon amide. These potent glucagon antagonists have among
      the highest pA(2) values of any glucagon analogs reported to date.

PMID- 11532075
TI  - Synthesis, activity on NK-3 tachykinin receptor and conformational solution
      studies of scyliorhinin II analogs modified at position 16.
AB  - Two analogs of a tachykinin family peptides - scyliorhinin II (ScyII):
      [Aib(16)]ScyII and [Sar(16)]ScyII were synthesized by the solid-phase method
      using Fmoc chemistry. Conformational studies in water and DMSO-d(6) on these
      peptides were performed using a combination of two-dimensional NMR and
      theoretical conformational analysis. The solution structure of the peptides
      studied is interpreted as an equilibrium of several conformers with different
      statistical weights. The structure of [Sar(16)]ScyII in water appeared to be more
      flexible, especially in the C-terminal fragment. A better defined structure for
      this analog was obtained in DMSO-d(6), in which the analysis resulted in a family
      of conformers with similar shapes. Some of these conformers were characterized by
      the presence of a 3(10)-helix in the N-terminal fragment and middle part of the
      molecule. The introduction of the Aib residue in position 16 significantly
      rigidifies the structure. For [Aib(16)]ScyII in both solvent systems very similar
      populations of conformations were obtained which are characterized by the
      presence of a 3(10)-helix in the 13-18 fragment. A common structural motif was
      found in conformationally constrained Cys(7)-Cys(13) fragment, which resembles
      the Greek letter 'omega'. The differences in the solution structure of the C
      terminal fragment of the peptides studied are responsible for their specificity.
      [Aib(16)]ScyII showed 25% the agonistic activity of selective NK-3 agonist -
      senktide, but it also showed antagonist effect vs. this peptide, whereas
      [Sar(16)]ScyII appeared to be a full agonist of NK-3 tachykinin receptor.

PMID- 11532076
TI  - Glutaraldehyde cross-linking alters the environment around Trp(29) of cobrotoxin
      and the pathway for regaining its fine structure during refolding.
AB  - Cobrotoxin, purified from the venom of Naja naja atra (Taiwan cobra), was
      subjected to modification with glutaraldehyde in order to prepare intra- and
      intermolecule cross-linked derivatives. Monomeric and dimeric derivatives were
      separated from polymeric derivatives by gel filtration. The results of amino acid
      analysis and sequence determination revealed that only Lys residues were
      selectively modified by glutaraldehyde. Glutaraldehyde cross-linking was
      accompanied by a change in the gross conformation of cobrotoxin as revealed by
      circular dichroism spectra of the modified derivatives. Compared with cobrotoxin,
      Trp(29) of monomeric and dimeric derivatives was in an apolar microenvironment.
      This was in agreement with acrylamide quenching studies showing that the spatial
      position of the Trp indole ring became buried in the interior of the molecule
      after glutaraldehyde cross-linking. Moreover, the Trp of modified derivatives was
      less accessible for iodide than that observed with cobrotoxin. Notably, disulfide
      reduction could not completely unfold the structure of glutaraldehyde-modified
      derivatives as evidenced by the results of acrylamide quenching studies and
      enzyme-linked immunoassay. Study of the characteristic changes in Trp
      fluorescence after the initiation of refolding suggested that the fine structure
      around Trp(29) of cobrotoxin and glutaraldehyde-modified derivatives was formed
      differently. These results suggest that glutaraldehyde cross-linking leads to a
      change in the microenvironment of cobrotoxin Trp(29) and alters the pathway of
      its fine structure formation during the refolding of cobrotoxin.

PMID- 11532077
TI  - O-Linked glycopeptides retain helicity in water.
AB  - A 17-residue O-linked glycopeptide model incorporating a central alpha-mannosyl
      serine residue, and its unglycosylated analog both demonstrate substantial
      helicity in water. The peptide sequence was derived from previous studies in
      which differences in overall helicity as a function of single amino acid
      substitutions were measured by circular dichroism (CD). The helical content was
      predicted by molecular modeling, and confirmed by CD and NMR. Moreover, the
      glycopeptide retained its helicity in the presence of SDS micelles, whereas the
      native peptide lost secondary structure in the presence of micelles. The
      inference is that the peptide sequence is a more important helix determinant than
      glycosylation per se.

PMID- 11532078
TI  - An appraisal of antiretroviral drugs in hemodialysis.
AB  - BACKGROUND: Acquired immunodeficiency syndrome (AIDS)-related kidney disorders
      concern 30% of those patients and can lead to end-stage renal disease (ESRD; 6 to
      10%). Therefore, the administration of antiretroviral drugs in human
      immunodeficiency virus (HIV) patients with nephropathy is not uncommon. METHODS:
      The influence of ESRD on the different phases of the pharmacokinetic profile of
      drugs in general is examined in light of bioavailability, distribution, protein
      binding, metabolism, and elimination. Then, the pharmacokinetics of
      antiretroviral drugs in hemodialysis are detailed. RESULTS: From these data,
      dosing recommendations are given for nucleoside reverse transcriptase inhibitors
      (NRTIs), non-NRTIs, and protease inhibitors (PIs). CONCLUSION: Dosage adjustments
      are often necessary for patients with renal insufficiency. These adaptations have
      to be carefully performed to optimize drug exposure and reduce the risk of side
      effects.

PMID- 11532079
TI  - Thrombotic microangiopathy, hemolytic uremic syndrome, and thrombotic
      thrombocytopenic purpura.
AB  - The term thrombotic microangiopathy (TMA) defines a lesion of vessel wall
      thickening (mainly arterioles or capillaries), intraluminal platelet thrombosis,
      and partial or complete obstruction of the vessel lumina. Depending on whether
      renal or brain lesions prevail, two pathologically indistinguishable but somehow
      clinically different entities have been described: the hemolytic uremic syndrome
      (HUS) and the thrombotic thrombocytopenic purpura (TTP). Injury to the
      endothelial cell is the central and likely inciting factor in the sequence of
      events leading to TMA. Loss of physiological thromboresistance, leukocyte
      adhesion to damaged endothelium, complement consumption, abnormal von Willebrand
      factor release and fragmentation, and increased vascular shear stress may then
      sustain and amplify the microangiopathic process. Intrinsic abnormalities of the
      complement system and of the von Willebrand factor pathway may account for a
      genetic predisposition to the disease that may play a paramount role in
      particular in familial and recurrent forms. Outcome is usually good in childhood,
      Shiga toxin-associated HUS, whereas renal and neurological sequelae are more
      frequently reported in adult, atypical, and familial forms of HUS and in TTP.
      Plasma infusion or exchange is the only treatment of proven efficacy. Bilateral
      nephrectomy and splenectomy may serve as rescue therapies in very selected cases
      of plasma resistant HUS or recurrent TTP, respectively.

PMID- 11532080
TI  - Influence of the renin-angiotensin system on epidermal growth factor expression
      in normal and cyclosporine-treated rat kidney.
AB  - BACKGROUND: Epidermal growth factor (EGF) plays an important role in renal
      tubular regeneration after ischemic injury in kidney. The present study reports
      the association between the renin-angiotensin system (RAS) and EGF, and the
      effect of angiotensin II blockade with losartan (LSRT) on EGF expression in an
      experimental model of chronic cyclosporine (CsA) nephrotoxicity in rats. METHODS:
      Two separate experiments were performed. In the first experiment, rats on the
      normal-salt diet (NSD; 0.3%) or low-salt diet (LSD; 0.05%) were treated with or
      without LSRT for four weeks. In the second experiment, rats on the NSD or LSD
      were given vehicle (VH group, olive oil, 1 mg/kg per day) or CsA (15 mg/kg per
      day) or CsA (15 mg/kg per day) plus LSRT (100 mg/L per day). Renal function,
      histopathology, TUNEL staining, plasma renin activity (PRA), and the expression
      of renin and EGF were studied. RESULTS: Normal rats on the LSD showed
      significantly increased EGF expression (cortex, 2.6-fold; medulla, 1.7-fold) and
      significantly decreased EGF expression with the LSRT treatment compared with the
      rats treated with the NSD (cortex, 74.8 vs. 10%; medulla, 22.5 vs. 5%). In
      contrast, the CsA-treated rats on the LSD had a significantly lower EGF
      expression (cortex, 98 vs. 53%; medulla, 94 vs. 14%); however, concomitant
      administration of LSRT increased the EGF expression (cortex, 91- vs. 3.8-fold;
      medulla, 19- vs. 2.4-fold) compared with the rats on the NSD. In the normal and
      CsA-treated LSD rats, EGF expression was well correlated with PRA. In addition,
      EGF expression was well correlated with the interstitial fibrosis score (r =
      0.664, P < 0.01) or number of TUNEL-positive cells (r = 0.822, P < 0.01) in CsA
      treated LSD rats. CONCLUSIONS: These results suggest that angiotensin II blockade
      with LSRT decreases EGF expression in normal rats on the LSD, but it protects EGF
      expression in CsA-induced nephrotoxicity. This finding provides a new perspective
      on the renoprotection of angiotensin II blockade in chronic CsA nephrotoxicity.

PMID- 11532081
TI  - Chronic exposure of human mesangial cells to high glucose environments activates
      the p38 MAPK pathway.
AB  - BACKGROUND: High glucose (HG) environments activate several protein kinase
      pathways in mesangial cells, including the mitogen-activated protein kinase
      (MAPK) pathway, ERK. The p38 MAPK pathway is activated by events that occur in
      the setting of diabetes, such as protein kinase C (PKC) up-regulation and
      cellular stresses (osmotic stress and redox changes). Substrates of activated p38
      MAPK include transcription factors that are involved in the microvascular
      complications of diabetes. This current study investigated the mechanisms of HG
      mediated activation of p38 MAPK in cultured human mesangial cells (HMCs) and the
      effects of p38 MAPK activation on the transcription factor activator protein-1
      (AP-1). METHODS: HMCs were cultured in 5 mmol/L D-glucose [normal glucose (NG)]
      or 30 mmol/L D-glucose (HG) for seven days. Cells were also treated with HG for
      brief periods of time (0.5 to 4 hours) to assess the acute effects of HG on p38
      MAPK. Using Western blotting of HMC lysates, changes in the tyrosine and
      threonine phosphorylation of p38 MAPK were measured. The kinase activity of
      immunoprecipitated p38 MAPK was determined by an in vitro assay that measured the
      phosphorylation and activation of MAPKAP kinase-2, an intermediary signaling
      protein downstream of p38 MAPK. To investigate the role of osmotic stress in HG
      activation of p38 MAPK, cells were acutely treated with mannitol (25 to 250
      mOsm/L x 5 to 60 min) or were grown seven days in media supplemented with
      mannitol at concentrations iso-osmotic to HG media. To investigate the role of
      PKC in HG-mediated p38 MAPK activation, HMCs were treated with the PKC inhibitors
      GF 109203X, Ro 32-0432, or rottlerin during the last several hours of HG
      treatment. HG conditioned cells were also treated with the antioxidants L-N
      acetylcysteine (L-NAC) or diphenyliodonium (DPI) prior to harvest. To determine a
      functional significance of HG-mediated p38 MAPK activation, the DNA binding of
      the transcription factor complex AP-1 was measured by electrophoretic mobility
      shift assay. RESULTS: The p38 MAPK pathway was not activated by the acute
      addition of HG to the HMCs. However, activation of p38 MAPK in HMCs grown seven
      days in HG was demonstrated by increased tyrosine and threonine phosphorylation
      of p38 MAPK proteins and increased kinase activity of immunoprecipitated p38
      MAPK. As assessed by a kinase assay, p38 MAPK activity in cells grown in HG for
      seven days exceeded that of NG cells by more than 250%. This difference was not
      due to differences in the amount of p38 MAPK protein between the treatment
      groups. Acute osmotic activation of p38 MAPK occurred at extremely high mannitol
      concentrations (250 mOsm/L) that exceeded the osmotic stress of acute HG.
      Furthermore, in cells grown for seven days in mannitol at concentrations similar
      to HG, p38 MAPK activity was similar to control values. Phorbol ester (PMA)
      treatment stimulated a twofold increase in p38 MAPK activity. The addition of GFX
      or Ro 32-0432 to HG cells, at concentrations that inhibited PMA activation of p38
      MAPK, did not inhibit the glucose-mediated p38 MAPK activation. Rottlerin, a PKC
      delta inhibitor, also failed to reverse the HG-mediated p38 MAPK activation.
      Treatment of HG cells with L-NAC or DPI inhibited the HG-mediated p38 MAPK
      phosphorylation. As we have previously shown, DNA binding of the transcription
      factor complex AP-1 was increased in HG cells. This binding was reversed by
      treatment of the HG cells with the p38 MAPK inhibitor SB 203580. CONCLUSIONS:
      Chronic exposure of HMC to HG concentrations activates the p38 MAPK pathway. This
      activation appears to be independent of changes in the amount of total p38 MAPK
      produced by the cells, independent of chronic osmotic stress and independent of
      PKC activation. The reversal of p38 MAPK by L-NAC and DPI suggests the glucose
      mediated p38 MAPK activation may occur via reactive oxygen species. The activity
      of AP-1, a transcription factor complex that regulates several genes involved in
      diabetic nephropathy, is reversed when the p38 MAPK pathway is inhibited. These
      findings suggest the p38 MAPK pathway may be an important pathway involved in
      diabetic complications.

PMID- 11532082
TI  - Dipyridamole inhibits PDGF-stimulated human peritoneal mesothelial cell
      proliferation.
AB  - BACKGROUND: It has been proposed that proliferation of human peritoneal
      mesothelial cells (HPMCs) accompanied by collagen synthesis may contribute to the
      development of peritoneal fibrosis (PF) in patients of long-term continuous
      ambulatory peritoneal dialysis (CAPD). However, the precise molecular mechanism
      regulating HPMC proliferation has never been reported. Dipyridamole has been
      reported to have potential as an antiproliferative and antifibrotic agent. We
      investigated the mechanism and effect of dipyridamole in regulation of HPMC
      proliferation. METHODS: HPMCs were cultured from human omentum by an enzyme
      digestion METHOD: Cell proliferation was measured by the methyltetrazolium assay
      and intracellular cAMP was measured using an enzyme immunoassay kit. Cell-cycle
      distribution of HPMC was analyzed by flow cytometry. Extracellular signal
      regulated protein kinase (p44/p42 ERK) activity and expressions of cell-cycle
      proteins (cyclin D(1), CDK4, pRB and p27(Kip1)) were determined by Western
      blotting. RESULTS: The addition of DP suppressed PDGF-stimulated HPMC
      proliferation by cell-cycle arrest at the G1 phase. The antimitogenic effect of
      dipyridamole was mediated through the cAMP pathway. PDGF (25 ng/mL) increased the
      ERK1/2 activity of HPMC within 15 minutes, which maximized at 30 minutes, and the
      pretreatment with dipyridamole (17 microg/mL) substantially reduced the ERK
      response to PDGF by approximately 78.5%. PDGF induced elevated protein levels of
      cyclin D(1), but the CDK4 protein level did not change. Dipyridamole and DBcAMP
      had no effect on the levels of cyclin D(1) and CDK4 in PDGF-stimulated HPMC. PDGF
      decreased p27(Kip1) and induced pRB phosphorylation of HPMC. In contrast,
      dipyridamole prevented PDGF-induced p27(Kip1) degradation and attenuated PDGF
      stimulated pRB phosphorylation. CONCLUSION: Dipyridamole appears to inhibit PDGF
      stimulated HPMC proliferation through attenuated ERK activity, preservation of
      p27(Kip1), and decreased pRB phosphorylation. Thus, dipyridamole may have
      therapeutic efficacy to prevent or alleviate PF.

PMID- 11532083
TI  - Abnormalities of Gq-mediated cell signaling in Bartter and Gitelman syndromes.
AB  - BACKGROUND: The constitutive endothelial isoform of nitric oxide synthase (ecNOS)
      and nitric oxide (NO) production are increased in patients with Bartter syndrome
      (BS) and Gitelman (GS) syndrome and may reduce vascular tone. Moreover, these
      patients present an abnormal cell signaling [reduced stimulated intracellular
      calcium ([Ca(2+)](i)) and inositol-1,4,5,triphosphate ([IP(3)](i)) in
      neutrophils], suggesting the presence of a generalized reduction of protein
      kinase C (PKC) and cell reactivity. Since PKC regulates ecNOS gene expression, we
      evaluated the signal transduction system involving Gq protein, PKC, and ecNOS in
      circulating nucleated cells from patients with BS/GS. METHODS: Nucleated blood
      cells from 2 BS and 7 GS and from 10 controls (C) were used. PKC activity was
      evaluated in neutrophils by radioenzymatic assay; PKC alpha concentration was
      evaluated in monocytes by Western blot analysis. ecNOS and G alpha q mRNA
      production was evaluated in monocytes by reverse transcription-polymerase chain
      reaction (RT-PCR) analysis using specific primers and quantitated by PCR-based
      semiquantitative analysis of ecNOS and G alpha q mRNA expression. RESULTS:
      Cytosol and membrane basal PKC activity were similar in neutrophils from BS/GS
      and C (70 +/- 3 vs. 80 +/- 2; 37 +/- 3 vs. 46 +/- 2 pmol/min/mg protein,
      respectively), while fMLP-stimulated membrane PKC activity increased to a lower
      extent in BS/GS (from 43 +/- 2 to 53 +/- 3 vs. 38 +/- 2 to 66 +/- 3 pmol/min/mg
      protein, P < 0.05 for the difference). Membrane PKC alpha expression was similar
      in basal conditions (8.5 +/- 1.5 vs. 12.4 +/- 4.0 densitometric units), but
      increased after fMLP was reduced in BS/GS (4.5 +/- 1.4 vs. 9.5 +/- 2.1, P <
      0.01). In BS/GS, PKC stimulation with PMA dose dependently reduced ecNOS gene
      expression (from 0.80 +/- 0.05 to 0.78 +/- 0.03 densitometric units; PMA 50
      nmol/L, P = NS; to 0.55 +/- 0.07, PMA 100 nmol/L, P < 0.001) to an undetectable
      expression (PMA 200 nmol/L). Qualitatively similar effects were seen in monocytes
      from control subjects. Incubation of monocytes from patients and controls with
      the PKC inhibitor GF109203X increased ecNOS mRNA, with no difference between
      patients and controls. G alpha q mRNA was reduced in BS/GS versus controls (0.87
      +/- 0.013 vs. 0.98 +/- 0.005 densitometric units, P < 0.0004). CONCLUSION: An
      abnormal G alpha q expression blunts cell signaling and PKC production in BS/GS.
      A reduced PKC up-regulated NO system may contribute to the vascular
      hyporeactivity of BS/GS.

PMID- 11532084
TI  - Differential expression of adenylyl cyclases in the rat nephron.
AB  - BACKGROUND: Adenylyl cyclases (ACs) are a family of enzymes that catalyze the
      formation of the second-messenger cyclic adenosine 3',5'-monophosphate (cAMP). At
      least nine isoforms of AC have been cloned. These isoforms differ in their tissue
      distribution and basal activity. AC isoforms also differ in their capacity to be
      stimulated or inhibited by G protein alpha(i), alpha(s) and beta/gamma subunits,
      protein kinase C, and intracellular calcium. The distribution of ACs in the
      kidney is only partially known, although it is known that ACs play important
      roles in kidney signal transduction. Several receptors are known to couple to AC,
      but their linkage to individual AC isoforms in the kidney is not known. METHODS:
      This study investigated the tissue distribution of AC isoforms along the nephron
      of Wistar-Kyoto rats using reverse transcription-polymerase chain reaction (RT
      PCR), immunohistochemistry, and immunoblotting. RESULTS: While AC VI and IX mRNA
      were found in all nephron segments, there was no expression of AC VIII mRNA. ACs
      II through V and VII mRNA were variably found in specific nephron segments. mRNA
      for AC isoforms II, III, VI, VII, and IX were expressed in renal proximal
      tubules. All of the AC isoforms studied, except VIII, were found in glomeruli.
      Immunoblotting and immunohistochemistry confirmed the mRNA results. AC isoforms
      II, III, IV, and IX were expressed in luminal rather than in basolateral
      membranes. However, immunohistochemical studies were not feasible for the other
      isoforms that could be expressed in basolateral membranes. CONCLUSION: Knowledge
      of the distribution of ACs may help establish the linkage between receptors and
      specific AC isoforms and define their functions.

PMID- 11532085
TI  - Glomerular complement regulation is overwhelmed in passive Heymann nephritis.
AB  - BACKGROUND: An injection of anti-Fx1A antibodies in rats leads to passive Heymann
      nephritis (PHN), a model of membranous nephropathy. Fx1A is a crude extract of
      renal cortex that contains megalin as a principal component. However, when rats
      are given anti-megalin antibodies, abnormal proteinuria does not occur. Because
      of the established complement dependence of PHN, we hypothesized that antibodies
      neutralizing complement regulatory proteins in the rat glomerulus also were
      required to induce PHN. Two likely targets are Crry and CD59, proteins abundant
      on the rat podocyte and contained within Fx1A that inhibit the C3 convertase and
      C5b-9 assembly, respectively. METHODS: Rats were injected with anti-megalin
      monoclonal antibodies, followed by anti-Crry and/or anti-CD59 F(ab')(2)
      antibodies five days later. In a second group of experiments, rats were injected
      with anti-Fx1A or anti-Fx1A immunodepleted of reactivity against Crry and/or
      CD59. RESULTS: In the setting of podocyte-associated anti-megalin monoclonal
      antibodies, simultaneous neutralization of Crry and CD59 function led to the
      development of significant proteinuria (11.0 +/- 2.1 mg/day, P < 0.001 vs. all
      other groups). In contrast, animals that had neither or only one of these
      complement regulators inhibited had normal urinary protein excretion (< or =6
      mg/day). In animals given anti-Fx1A depleted of anti-Crry and/or anti-CD59, all
      groups developed typical PHN, characterized by heavy proteinuria and extensive
      glomerular deposition of C3 and C5b-9. CONCLUSION: Crry and CD59 play an
      important role in restraining complement-mediated injury following subepithelial
      immune complex deposition; however, in PHN, their regulatory capacity is
      overwhelmed.

PMID- 11532086
TI  - Sequential analysis of kidney stone formation in the Aprt knockout mouse.
AB  - BACKGROUND: We have previously shown that, as in human adenine
      phosphoribosyltransferase (APRT) deficiency, Aprt knockout mice form 2,8
      dihydroxyadenine (DHA) renal stones. The disease develops earlier and is more
      severe in male than in female mice. To examine the biological bases for these
      differences, the area occupied by DHA crystals was quantified in kidney sections
      from male and female mice (strain 129) aged one day to eight months and this
      parameter was correlated with changes in renal histopathology. Aprt heterozygous
      and wild-type mice were used as controls. METHODS: Following anesthesia, the left
      kidney was removed and immediately frozen in dry ice. Unstained cryosections were
      examined by polarized light to determine total area of birefringent particles.
      The right kidney was perfused and embedded in plastic, and stained sections were
      viewed by light microscopy to examine the histopathology and to determine the
      location of the birefringent particles. A pathological score was assigned to the
      histological findings. The scores from the right kidney were compared with
      crystal/particle area in the left kidney, and the data were analyzed using two
      way analysis of variance. The chemical composition of the particles was
      determined by x-ray diffraction analysis. Several stone fragments from the
      bladder were also examined by scanning electron microscopy (SEM). RESULTS:
      Crystals were detected in kidney sections from one- to two-day-old Aprt knockout
      mice. The crystal burden remained low in both sexes throughout the study except
      in males at the 120- to 240-day period. Furthermore, there was a substantial
      degree of renal pathology, primarily seen as interstitial fibrosis, in those
      males with a very high level of stone formation. The crystalline material was
      identified as 6-amino-2,8(3,9)-purine dione, a tautomeric form of DHA. SEM
      indicated that the crystals were spherical, with a diameter of 10 to 20 microm.
      Tissue staining and fixation procedures dramatically reduced the amount of
      birefringent material in kidney sections. Aprt heterozygotes of both sexes had
      low levels of crystalline material in the kidneys and no pathology. Birefringent
      material or pathological changes were not seen in kidneys from wild-type mice.
      CONCLUSIONS: Both male and female Aprt knockout mice accumulate DHA. However, the
      area occupied by DHA crystals was significantly greater in 120- to 240-day-old
      males compared with the females of similar age. Also, substantial renal pathology
      was detected in kidneys of male mice that had very high levels of stone material.

PMID- 11532087
TI  - Renal cell apoptosis in chronic obstructive uropathy: the roles of caspases.
AB  - BACKGROUND: Apoptosis of tubular and interstitial cells is well documented in
      kidneys with chronic obstructive uropathy (COU) and probably plays an important
      role in the pathogenesis of this condition. The molecular control of apoptosis in
      COU remains poorly understood. Apoptosis in general is known to proceed initially
      along distinct pathways, which later converge into a common arm characterized by
      orderly activation of caspases. Caspases are cytosolic enzymes that belong to a
      12-member family and serve as effector molecules for apoptosis. The role of
      individual caspases in mediating renal cell apoptosis in kidneys with COU is
      studied. METHODS: Kidneys were harvested from sham-operated mice and mice with
      COU created by left ureter ligation at days 4, 7, 15, 20, and 30. The following
      studies were performed: (1) determination of dried kidney weight; (2) in situ end
      labeling of fragmented DNA to detect apoptotic tubular and interstitial cells;
      (3) ribonuclease protection assay with specific anti-sense RNA probes for
      caspases 1, 2, 3, 6, 7, 8, 9, 11, and 12 to detect the expression of individual
      caspases; (4) immunostaining for caspases; and (5) assay for caspase 3. To assess
      the role of caspases in COU-associated renal cell apoptosis, the frequencies of
      apoptotic tubular and interstitial cells were separately quantitated for each
      experimental time point, and their patterns of variation were correlated with
      those of individual caspases. RESULTS: The obstructed kidneys showed progressive
      tissue loss (60% of control at day 15). Apoptosis of both tubular and
      interstitial cells was seen in obstructed kidneys. Tubular cell apoptosis peaked
      at four days after ureter ligation (13-fold of control), remained high between
      days 4 to 15, and thereafter decreased rapidly. Apoptotic interstitial cells were
      scanty initially, but gradually increased throughout the entire experiment.
      Apoptosis was minimal throughout the experiment in control and contralateral
      kidneys. In control and contralateral kidneys, caspases 2, 3, 6, 7, 8, and 9
      mRNAs were expressed at low levels, whereas those for caspases 1, 11, and 12 were
      not detected. The obstructed kidneys displayed increased expression of all tested
      caspases. Caspases 1, 11, and 12 mRNAs were detected in obstructed kidneys in a
      common pattern characterized by a sharp increase at day 4, followed by a decrease
      until day 20, and a subsequent sharp increase until the end of the study at day
      30. A similar pattern was noted for other caspases (2, 3, 6, 7, 8, and 9), which
      maximally reached twofold to fourfold that of controls. Immunostaining for
      caspases 1, 2, 3, 6, 7, 8, and 9 showed the same pattern characterized by focal
      and weak expression in proximal tubules of control or contralateral kidney,
      contrasting with increased staining in atrophic or dilated tubules of obstructed
      kidneys. Interstitial cells also displayed staining for several caspases, which
      paralleled the increasing density of interstitial cells toward the end of the
      experiment. Caspase-3 assay showed a marked increased activity in obstructed
      kidneys that reached fourfold and sevenfold of control at days 4 and 30,
      respectively. The rise and fall of caspase mRNAs between days 4 and 30 paralleled
      a similar fluctuation in tubular cell apoptosis. The subsequent increase of mRNAs
      was correlated with a continuous rise of interstitial cell apoptosis.
      CONCLUSIONS: Urinary obstruction in mice induces apoptosis of both tubular and
      interstitial cells in the affected kidney in a distinctive pattern that parallels
      an increased expression of caspases. This correlation suggests that these
      caspases mediate COU-associated renal cell apoptosis. Among the evaluated
      caspases, increased renal caspase 3 activity implies its central role in renal
      cell apoptosis associated with urinary obstruction.

PMID- 11532088
TI  - Low-molecular-weight heparin prevents high glucose- and phorbol ester-induced TGF
      beta 1 gene activation.
AB  - BACKGROUND: Hyperglycemia-induced overexpression of prosclerotic transforming
      growth factor-beta 1 (TGF-beta 1) has been implicated in the pathogenesis of
      diabetic nephropathy. Since previous in vivo studies demonstrated a
      renoprotective effect of low-molecular-weight (LMW) heparin in experimental
      animals, and recent in vitro data showed an interaction of this drug with the
      overactivated TGF-beta 1 cascade in high glucose- and phorbol ester-stimulated
      mesangial cells, we studied the molecular mechanism of these effects on TGF-beta
      1 gene expression. METHODS: Mesangial cells were stimulated with 30 mmol/L
      glucose or with 0.5 micromol/L phorbol ester [phorbol myristate acetate (PMA)] in
      the absence or presence of LMW heparin. TGF-beta 1 promoter activity was
      determined in promoter-reporter luciferase assays. The effect of LMW heparin on
      the binding of nuclear proteins to a regulatory activator protein-1 (AP-1) site,
      which mediates the high glucose and PMA responsiveness of the TGF-beta 1
      promoter, was studied by electrophoretic mobility shift assays. RESULTS: The
      presence of LMW heparin completely prevented TGF-beta 1 gene activation in both
      high glucose- and PMA-stimulated cells. Preincubation of the cells with LMW
      heparin and subsequent stimulation of the cells with both stimuli yielded the
      same result. Furthermore, treatment with LMW heparin prevented the enhanced
      binding of nuclear proteins to the regulatory AP-1 site, while binding to a Sp1
      site was unaffected. Basal promoter activity and basal AP-1 binding also was
      reduced by LMW heparin. The LMW heparin effect on basal promoter activity was
      abolished by mutation of the regulatory AP-1 box B and by deletion of this AP-1
      binding site. CONCLUSIONS: LMW heparin prevents high glucose- and PMA-mediated
      TGF-beta 1 expression by inhibiting the activation of the TGF-beta 1 promoter and
      by preventing the enhanced binding of nuclear proteins to the regulatory AP-1
      site.

PMID- 11532089
TI  - P glycoprotein-mediated cholesterol cycling determines proximal tubular cell
      viability.
AB  - BACKGROUND: MDR P glycoproteins may help transport plasma membrane free
      cholesterol (FC) to the endoplasmic reticulum (ER), where it undergoes acylation,
      forming cholesterol esters (CE). This study assessed whether P glycoprotein
      inhibitors alter renal tubular FC/CE expression, thereby altering cell integrity.
      METHODS: Mouse proximal tubule segments (PTS) were exposed to chemically
      dissimilar P glycoprotein inhibitors [progesterone (prog), trifluoperazine (TFP),
      or cyclosporine A (CsA)]. Their effects on FC/CE and adenosine 5'-triphosphate
      (ATP) levels, phospholipid expression, lipid peroxidation, and cell viability
      (lactate dehydrogenase release; LDH) were assessed. P glycoprotein inhibitor
      effects on cultured proximal tubular (HK-2) cell viability and susceptibility to
      Fe-induced oxidant stress were also addressed. RESULTS: When applied to PTS,
      prog, TFP, and, to lesser extent, CsA induced dose-dependent ATP reductions (< or
      =90%), CE decrements (approximately 40%), and LDH release (< or =60%). No
      concomitant changes in lipid peroxidation or phospholipid profiles were observed.
      Ouabain did not preserve tubular ATP, suggesting that decreased ATP production,
      rather than increased consumption, was operative. Mechanisms leading to cell
      lysis were not identical, as glycine and arachidonic acid blocked prog- but not
      TFP-mediated cell death. When prog-driven CE reductions were attenuated in PTS
      with a procycling agent (cholesterol oxidase), decreased cell death resulted. P
      glycoprotein inhibitors also caused dose-dependent HK-2 cell death. Blocking Fe
      mediated CE formation ( approximately x10) with sublethal CsA doses led to a
      marked increase in Fe-mediated cell death. CONCLUSIONS: P glycoproteins may be
      critical to tubule cholesterol transport. If blocked with pharmacologic agents,
      decreased ATP production, overt cell lysis, and/or a marked propensity to
      superimposed tubular cell injury can result.

PMID- 11532090
TI  - Podocyte depletion and glomerulosclerosis have a direct relationship in the PAN
      treated rat.
AB  - BACKGROUND: Podocytes are highly differentiated glomerular epithelial cells with
      limited potential to divide. They are responsible for maintaining and supporting
      the glomerular basement membrane so as to facilitate efficient filtration. The
      hypothesis tested was whether the development of glomerulosclerosis in the
      puromycin aminonucleoside (PAN)-treated rat could be attributed to podocyte
      depletion. METHODS: PAN was injected in Sprague-Dawley rats once, twice, or three
      times at 30-day intervals. Podocytes were counted in glomeruli using
      immunoperoxidase histochemistry and antibodies to both GLEPP1 (PTPRO) and WT-1.
      Podocytes were assayed in urine using reverse transcription-quantitative
      polymerase chain reaction (RT-QPCR). Glomerular areas were measured by
      computerized morphometry. RESULTS: In a preliminary experiment, a single
      injection of PAN caused a reduction in the glomerular podocyte count by 25%.
      Additional independent confirmation that podocytes were lost from glomeruli after
      PAN injection was obtained identifying detached podocytes in Bowman's space,
      measurement of nephrin and GLEPP1 mRNAs in urine, ultrastructural analysis of
      glomeruli, and identification of TUNEL-positive apoptotic podocytes in glomeruli.
      In a second experiment, sequential podocyte depletion by 15, 31, and 53% was
      achieved by the administration of one, two, or three injections of PAN at 30-day
      intervals. The region of the glomerulus devoid of podocytes developed
      glomerulosclerosis, and this area progressively increased as podocytes were
      progressively depleted. The correlation coefficient (r(2)) value for the
      relationship between percent podocyte depletion and glomerulosclerotic area was
      0.99. The Y intercept of this plot showed that glomerulosclerosis was initiated
      when only 10 to 20% of podocytes were lost. CONCLUSION: This report supports the
      growing body of data linking glomerulosclerosis directly to a reduction in
      relative podocyte number [increased glomerular area per podocyte (GAPP)]. It
      raises important questions related to the mechanisms of podocyte loss, strategies
      for prevention of podocyte depletion, and the prevention of progression of
      glomerular diseases.

PMID- 11532091
TI  - Mesangial IgA1 in IgA nephropathy exhibits aberrant O-glycosylation: observations
      in three patients.
AB  - BACKGROUND: In IgA nephropathy (IgAN), circulating IgA1 molecules display an
      abnormal pattern of O-glycosylation. This abnormality may potentially contribute
      to mesangial IgA1 deposition, but this is unproven because the O-glycosylation of
      mesangial IgA1 has not been analyzed. METHODS: IgA1 was eluted from glomeruli
      isolated from the kidneys of three IgAN patients obtained after nephrectomy or at
      postmortem. Serum from these patients, other patients with IgAN, and controls was
      subjected to the same treatment as the glomerular eluates. The O-glycosylation of
      eluted and serum IgA1 was measured by lectin binding using an enzyme-linked
      immunosorbent assay-based system. RESULTS: In all three cases, the lectin binding
      of IgA1 eluted from the glomeruli of IgAN patients was markedly higher than that
      of the serum IgA1 of the same individual, and also all but one of a series of
      serum IgA1 samples from other patients and controls. CONCLUSIONS: The higher
      lectin binding of glomerular compared with serum IgA1 suggests that O
      glycosylated IgA1 molecules abnormally and selectively deposit in the kidney.
      These results provide the first evidence that mesangial IgA1 is abnormally O
      glycosylated, and support a direct role for abnormal IgA1 O-glycosylation in the
      mechanism of mesangial IgA deposition in IgAN.

PMID- 11532092
TI  - Effect of age and biopsy site on extracellular matrix mRNA and protein levels in
      human kidney biopsies.
AB  - BACKGROUND: Investigation of the prognostic value of the expression of mRNA for
      extracellular matrix (ECM) components with respect to deterioration of kidney
      function in patients with renal disease requires an evaluation of the basal
      expression of ECM mRNA in healthy individuals and of the reliability of ECM mRNA
      measurements. In the current study, the collagen alpha 1(IV)/GAPDH (C4:G) and
      collagen alpha 1(I)/GAPDH (C1:G) mRNA ratios and the accumulation of collagen IV
      and collagen I protein were investigated in renal cortices of individuals of
      various age. Furthermore, we examined whether the C4:G mRNA ratio measured in a
      renal biopsy is representative of that in the rest of the kidney. METHODS: To
      investigate the effect of age on collagen expression, kidneys obtained at autopsy
      from patients with a normal renal function (N = 18; age 19 to 92) were used. C4:G
      and C1:G mRNA ratios were measured by real-time polymerase chain reaction (PCR)
      analysis. Accumulation of collagen IV and collagen I protein was measured by
      quantitative image analysis on immunohistochemically stained sections. To
      determine whether the site at which a biopsy is taken affects the C4:G mRNA
      ratio, this ratio was measured in cortical biopsies taken from different
      locations from each of four kidneys: one without renal disease, one with diabetes
      mellitus type I, and two with diabetes mellitus type II. C4:G mRNA ratios were
      measured by using real-time PCR. RESULTS: The C4:G mRNA ratio, but not the C1:G
      mRNA ratio or collagen IV protein accumulation, increased significantly with age
      (r = 0.55, P < 0.03). Collagen I protein accumulation increased with age (r =
      0.85, P < 0.001) and correlated with the extent of interstitial fibrosis (r =
      0.50, P < 0.05). The C4:G mRNA ratio did not differ significantly within a
      kidney. CONCLUSIONS: This report shows, to our knowledge for the first time, that
      in the aging, normally functioning human kidney, there is a dissociation between
      the levels of mRNA for collagen IV and collagen I and the accumulation of these
      proteins. The levels of mRNA for collagen IV in a single renal biopsy can be
      regarded as representative of those in the rest of the kidney. These observations
      should be taken into account when ECM mRNA levels are used for diagnostic
      purposes.

PMID- 11532093
TI  - Up-regulation of parathyroid hormone-related protein in folic acid-induced acute
      renal failure.
AB  - BACKGROUND: Parathyroid hormone (PTH)-related protein (PTHrP) is present in many
      normal tissues, including the kidney. Current evidence supports that PTHrP is
      involved in renal pathophysiology, although its role on the mechanisms of renal
      damage and/or repair is unclear. Our present study examined the changes in PTHrP
      and the PTH/PTHrP receptor (type 1) in folic acid-induced acute renal failure in
      rats. The possible role of PTHrP on the process of renal regeneration following
      folic acid administration, and potential interaction between angiotensin II (Ang
      II) and endothelin-1, and PTHrP, were examined in this animal model. METHODS:
      PTHrP, PTH/PTHrP receptor, ACE, and preproendothelin-1 (preproET-1) mRNA levels
      in the rat kidney were analyzed by reverse transcription-polymerase chain
      reaction (RT-PCR) and/or RNase protection assay. Immunohistochemistry also was
      performed for PTHrP, the PTH/PTHrP receptor, and Ang II in the renal tissue of
      folic acid-injected rats. The role of PTHrP on tubular cell proliferation
      following folic acid injury was investigated in vitro in rat renal epithelial
      cells (NRK 52E). PTHrP secretion in the medium conditioned by these cells was
      measured by an immunoradiometric assay specific for the 1-36 sequence. RESULTS:
      Using RT-PCR, PTHrP mRNA was rapidly (1 hour) and maximally increased (3-fold) in
      the rat kidney after folic acid, decreasing after six hours. At 72 hours, renal
      function was maximally decreased in these rats, associated with an increased
      PTHrP immunostaining in both renal tubules and glomeruli. In contrast, the
      PTH/PTHrP receptor mRNA (RNase protection assay) decreased shortly after folic
      acid administration. Moreover, PTH/PTHrP receptor immunostaining dramatically
      decreased in renal tubular cell membranes after folic acid. A single subcutaneous
      administration of PTHrP (1-36), 3 or 50 microg/kg body weight, shortly after
      folic acid injection increased the number of tubular cells staining for
      proliferating cell nuclear antigen by 30% (P < 0.05) or 50% (P < 0.01),
      respectively, in these rats at 24 hours, without significant changes in either
      renal function or calcemia. On the other hand, this peptide failed to modify the
      increase (2-fold over control) in ACE mRNA, associated with a prominent Ang II
      staining into tubular cell nuclei, in the kidney of folic acid-treated rats at
      this time period. The addition of 10 mmol/L folic acid to NRK 52E cells caused a
      twofold increase in PTHrP mRNA at six hours, without significant changes in the
      PTH/PTHrP receptor mRNA. The presence of two anti-PTHrP antibodies, with or
      without folic acid, in the cell-conditioned medium decreased (40%, P < 0.01) cell
      growth. CONCLUSIONS: Renal PTHrP was rapidly and transiently increased in rats
      with folic acid-induced acute renal failure, featuring as an early response gene.
      In addition, changes in ACE and Ang II expression were also found in these
      animals. PTHrP induces a mitogenic response in folic acid-damaged renal tubular
      cells both in vivo and in vitro. Our results support the notion that PTHrP up
      regulation participates in the regenerative process in this model of acute renal
      failure and is a common event associated with the mechanisms of renal injury and
      repair.

PMID- 11532094
TI  - Hexamethylene bisacetamide protects peritoneal mesothelial cells from glucose.
AB  - BACKGROUND: Peritoneal dialysis causes damage to peritoneal mesothelial cells
      primarily because dialysis fluids have a high glucose concentration. This study
      examined the abnormalities of gap junctional intercellular communication (GJIC)
      in human peritoneal mesothelial cells (HPMCs) exposed to relatively high levels
      of glucose. Also, ability of hexamethylene bisacetamide (HMBA) to up-regulate
      GJIC in HPMCs exposed to high levels of glucose was measured. METHODS: An assay
      that monitors the recovery of fluorescence after photobleaching was used to
      measure GJIC in primary cultured HPMCs. The cells were exposed to a low (10
      mmol/L) or high (50 or 90 mmol/L) glucose level for a total of six days, and some
      cells were also incubated with or without HMBA (1 or 6 mmol/L) from day 4. The
      effects of incubation in these various environments on expression of the connexin
      43 (Cx43) gene were investigated by the reverse transcription-polymerase chain
      reaction (to detect Cx43 mRNA) or by immunofluorescence and Western blotting (to
      detect Cx43 protein). To evaluate the influence of protein kinase C (PKC) or
      mitogen-activated protein kinase (MAPK) on GJIC, specific inhibitors were added
      to cultures in a high glucose medium. RESULTS: Gap junctional intercellular
      communication was inhibited in a concentration- and time-dependent manner when
      cells were exposed to high glucose. The addition of 6 mmol/L HMBA to cultures
      significantly enhanced GJIC despite the presence of a high glucose concentration.
      High glucose also down-regulated Cx43 mRNA and protein expression, with the dose
      dependent decrease of Cx43 protein at gap junctions paralleled by a decrease in
      the phosphorylation of this protein. As expected, treatment of cells with 6
      mmol/L HMBA increased both Cx43 mRNA and protein levels despite exposure to high
      glucose. The addition of PKC or MAPK inhibitors to high glucose cultures did not
      restore GJIC, and there was no significant change of Cx43 phosphorylation in the
      presence of these inhibitors. CONCLUSIONS: High glucose down-regulates GJIC in
      human peritoneal mesothelial cells. It also decreases the levels of both Cx43
      mRNA and Cx43 protein, with the latter becoming hypophosphorylated. HMBA appears
      to reverse all of these changes. These results are consistent with our hypothesis
      that HMBA protects HPMCs from the adverse effects of high glucose by reversing
      various processes that would otherwise lead to harmful loss of GJIC.

PMID- 11532095
TI  - Coagulation process proceeds on cultured human mesangial cells via expression of
      factor V.
AB  - BACKGROUND: In a previous clinicopathological study, we observed mesangial factor
      V expression accompanied by the intact form of cross-linked fibrin deposition in
      the active type of IgA nephropathy. The conversion of prothrombin to thrombin by
      factor Xa is potently accelerated more than 104-fold by the presence of factor V,
      which is a membrane-bound cofactor. Another membrane-bound cofactor, tissue
      factor, is known to play an initiating role in the coagulation cascade and to be
      synthesized in mesangial cells (MCs) by the stimulation of tumor necrosis factor
      alpha (TNF-alpha). However, the synthesis of factor V, which plays on the
      terminating stage of prothrombin activation, has not been reported previously in
      MCs by in vitro study. Our current study tested the coagulation process via
      expression of factor V by the stimulation of proinflammatory cytokine, TNF-alpha,
      in cultured human MCs. METHODS: To evaluate factor V protein expression,
      immunoperoxidase staining with densitometric evaluation and Western blot analysis
      were conducted after stimulation of TNF-alpha. To test factor V activity,
      stimulated MCs were incubated in combination with factor Xa, prothrombin,
      fibrinogen and factor XIII, and fibrin production on MCs was assessed after
      immunoperoxidase staining on the cell surface. In a blocking test using an
      antibody against factor V, suppression of fibrin production was evaluated to
      clarify the role of factor V activity. For the evaluation of factor V mRNA
      expression in cultured human MCs, in situ hybridization and Northern blot
      analysis were performed. RESULTS: Factor V protein expression in MCs after TNF
      alpha stimulation increased both time- and dose-dependently. As a marker of
      factor V activity with exogenous factor Xa, fibrin production on TNF-alpha
      stimulated MCs was increased in a time-dependent manner and was inhibited by the
      addition of anti-factor V antibody. Factor V mRNA was identified in MCs by in
      situ hybridization and showed an increase after stimulation with TNF-alpha on
      Northern blot analysis. CONCLUSIONS: Our data suggest that the coagulation
      process proceeds on MCs as the result of increased expression of endogenous
      factor V activity on its cell surface in cooperation with exogenous factor Xa.

PMID- 11532096
TI  - Intravenous immunoglobulin protects against experimental thrombotic
      microangiopathy.
AB  - BACKGROUND: Intravenous immunoglobulin (IVIG) has been utilized in several forms
      of vasculitis and has many potential mechanisms of action, including the
      inhibition of C3 activation. We have previously demonstrated that IVIG can reduce
      glomerular injury in a model of membranous nephropathy mediated by C5b-9 [1]. C5b
      9 has also been shown to mediate the thrombotic microangiopathy (TMA) induced by
      antibody to glomerular endothelial cells leading to a hemolytic uremic syndrome
      type lesion [2]. METHODS: To test the hypothesis that IVIG might be effective in
      treating antibody-induced TMA, male uninephrectomized rats underwent right renal
      artery perfusion with goat anti-rat glomerular endothelial cell (GEN) antibody
      (20 mg/kg). Sheep IgG (200 mg/kg) was administered either 30 minutes before the
      renal artery perfusion (group I, N = 6) or 30 minutes postperfusion (group II, N
      = 9). A third control group received phosphate-buffered saline (PBS; group III, N
      = 12). A survival biopsy was performed at 15 minutes, and the animals were
      sacrificed on day 2. RESULTS: There were no significant differences in
      proteinuria or hematocrit between the groups. Animals pretreated with IVIG had
      significantly improved survival and renal function, which was associated with a
      decrease in glomerular C3 deposition. The protective effect of IVIG was abolished
      if the administration was delayed 30 minutes after perfusion. CONCLUSIONS: IVIG
      is effective in reducing injury in experimental TMA only if given
      prophylactically. The effect is mediated by inhibition of local intraglomerular
      complement activation.

PMID- 11532097
TI  - Effect of shigatoxin-1 on arachidonic acid release by human glomerular epithelial
      cells.
AB  - BACKGROUND: Altered arachidonic acid (AA) metabolism has been implicated in the
      pathogenesis of renal injury in the hemolytic uremic syndrome (HUS). However,
      there is very little information of the effect of shigatoxin (Stx; the putative
      mediator of renal damage in HUS) on AA release or metabolism by renal cells.
      Since recent studies have demonstrated that glomerular epithelial cells (GECs)
      may be important early targets of Stx, the current study was undertaken to
      examine the effects of Stx on AA release and metabolism by GECs. METHODS:
      Cultured human GECs were exposed to Stx1 +/- lipopolysaccharide (LPS) for 4 to 48
      hours followed by determination of (3)H-arachidonate release, thromboxane A(2)
      (TxA(2)) and prostacyclin (PGI(2)) production, cyclooxygenase (COX) activity, and
      Western and Northern analyses for phospholipase A(2) (PLA(2)) and COX protein and
      mRNA levels, respectively. RESULTS: Stx1 increased arachidonate release by GECs.
      LPS alone had no such effect, but increased arachidonate release in response to
      Stx1. Stx1-stimulated arachidonate release correlated with elevations in cPLA(2)
      and sPLA(2) protein and cPLA(2) mRNA levels. Stx1 also increased both TxA(2) and
      PGI(2) production by GECs; LPS alone did not alter eicosanoid production, but
      augmented Stx1 effects. Both Stx1 and LPS stimulated COX activity; however, these
      effects were not additive. Although there was an accompanying elevation of COX-1
      and COX-2 mRNA, Stx1 decreased and LPS did not change COX1 and COX2 protein
      levels. CONCLUSIONS: Stx1 alone or in conjunction with LPS increases arachidonate
      release and eicosanoid production by human GECs; this effect correlates with
      increased PLA(2) protein and mRNA levels. To our knowledge, this is the first
      study identifying the mechanisms of Stx1-stimulated AA release. These results
      raise the possibility that arachidonate release and metabolism by GECs, and
      conceivably other renal cell types, are involved in renal injury in HUS.

PMID- 11532098
TI  - Glomerular endothelial cells and podocytes jointly synthesize laminin-1 and -11
      chains.
AB  - BACKGROUND: The glomerular basement membrane (GBM) originates in development from
      fusion of subendothelial and subepithelial matrices. Subsequently, newly
      synthesized subepithelial matrix is added as glomerular capillary loops expand.
      During GBM assembly, the laminin-1 heterotrimer (alpha 1, beta 1, and gamma 1
      chains), initially expressed in vascular clefts of comma- and S-shaped bodies, is
      eventually replaced by laminin-11 (alpha 5, beta 2, and gamma 1 chains), which
      persists into maturation. The cellular source(s) of these laminins is not known
      and prompted this study. METHODS: To determine which cells synthesize the various
      laminin chains, postfixation immunoelectron microscopy of developing mouse kidney
      was performed using monoclonal and polyclonal antibodies that specifically
      recognized laminin alpha 1, beta 1, alpha 5, or beta 2 chains. RESULTS:
      Intracellular labeling for laminin alpha 1, beta 1 (laminin-1), and alpha 5 and
      beta 2 (laminin-11) chains was observed in developing glomerular endothelial
      cells and podocytes of comma- and S-shaped nephric figures. Laminin-1 was also
      seen in unfused GBMs at this stage, whereas laminin-11 was only found
      intracellularly. In capillary loop stage GBMs, laminin alpha 1 chain was
      completely absent, whereas labeling for laminin alpha 5 was intense, indicating
      rapid substitution between alpha chains. In contrast, laminin beta 1 chain
      labeling remained strong both intracellularly and in GBMs of capillary loop stage
      glomeruli, and beta 2 was up-regulated as well. In maturing stage glomeruli, beta
      1 labeling declined, and alpha 5 and beta 2 remained at high levels
      intracellularly in both endothelial cells and podocytes and in GBMs. CONCLUSIONS:
      Our results show that both endothelial cells and podocytes synthesize laminin-1
      and -11 chains throughout glomerular development. The sustained and comparatively
      high level of laminin synthesis by endothelial cells was unexpected, suggesting
      that the endothelium may be an important source of GBM proteins in glomerular
      disease.

PMID- 11532099
TI  - Acute cholestatic liver disease protects against glycerol-induced acute renal
      failure in the rat.
AB  - BACKGROUND: It is widely held that liver disease predisposes toward acute tubular
      necrosis. The present study examines the effect of acute cholestatic liver
      disease on the susceptibility to glycerol-induced acute tubular necrosis in the
      rat. METHODS: Acute cholestatic liver disease was induced by ligation of the
      common bile duct, while the intramuscular injection of hypertonic glycerol was
      used to induce acute tubular necrosis. Renal injury was assessed by plasma
      creatinine concentration and renal histology. An in vitro model of heme protein
      induced renal injury (hemoglobin in conjunction with glutathione depletion) was
      employed to assess the cytoprotective effects of bilirubin. RESULTS: Ligation of
      the common bile duct markedly reduced acute renal injury that occurs in the
      glycerol model (7.5 mL/kg body weight), as evidenced by a lower plasma creatinine
      concentration and less severe renal histologic injury. At a higher dose of
      glycerol (10 mL/kg body weight), ligation of the common bile duct again reduced
      renal injury and cumulative mortality that occurs five days after the induction
      of this model of acute renal failure. These protective effects of ligation of the
      common bile duct could not be ascribed to less severe muscle injury or red cell
      damage. Ligation of the common bile duct induced heme oxygenase-1 in the kidney
      and markedly so in the liver. Inhibition of heme oxygenase significantly
      attenuated, but did not prevent, the protective effects conferred by ligation of
      the common bile duct. Bilirubin, in low micromolar concentrations, was
      cytoprotective against heme protein-induced cell injury in vitro. CONCLUSIONS:
      Ligation of the common bile duct confers resistance to glycerol-induced acute
      tubular necrosis in the rat, actions that arise, in part, from the induction of
      heme oxygenase-1 in the kidney and liver. Bilirubin, in micromolar
      concentrations, protects against heme protein-induced renal injury. Our studies
      uncover a novel form of acquired resistance to renal injury, occurring,
      unexpectedly, in the setting of acute cholestatic liver disease. We speculate
      that such potentially cytoprotective alterations may safeguard the kidney against
      irreversible functional and structural injury in the hepatorenal syndrome.

PMID- 11532100
TI  - Role of kidney-specific organic anion transporters in the urinary excretion of
      methotrexate.
AB  - BACKGROUND: High-dose folinic acid is used to accelerate methotrexate elimination
      to avoid renal toxicity of the drug. The present study was carried out to examine
      the role of the renal organic anion transporters OAT-K1 and OAT-K2 in the urinary
      excretion of methotrexate, especially in the methotrexate-folinic acid rescue
      therapy. METHODS: Madin-Darby canine kidney cells stably expressing OAT-K1 and
      OAT-K2 were used for the in vitro transport study; 5/6 nephrectomized rats were
      used to detect changes in mRNA expression levels of OAT-K1 and OAT-K2 and to
      evaluate methotrexate pharmacokinetics under conditions of renal insufficiency.
      RESULTS: Methotrexate efflux mediated by these transporters in stable
      transfectants was stimulated in the presence of extracellular folic acid and
      folinic acid, suggesting that they could serve as anion exchangers to enhance the
      apical efflux of methotrexate. The mRNA expression levels of OAT-K1 and OAT-K2
      were markedly diminished after 5/6 nephrectomy, but those of multidrug resistance
      associated protein 2, which could transport methotrexate, were maintained. Renal
      clearance of methotrexate was markedly decreased in 5/6 nephrectomized rats
      compared with that in sham-operated rats. Additional folinic acid treatment
      resulted in a significant increase in methotrexate renal clearance in sham
      operated rats but not in 5/6 nephrectomized rats. CONCLUSIONS: The decreased
      expressions of OAT-K1 and OAT-K2 may be attributable to the longer exposure to
      methotrexate and ineffective folinic acid rescue. In terms of contributing to
      patient safety, renal clearance of methotrexate, especially folinic acid
      stimulated tubular secretion of the drug via these transporters, would be a key
      factor in methotrexate therapy.

PMID- 11532101
TI  - P-glycoprotein inhibitors stimulate renal phosphate reabsorption in rats.
AB  - BACKGROUND: Dipyridamole (Dip) was previously shown to increase renal phosphate
      (Pi) reabsorption in humans. However, the mechanism(s) underlying this renal
      tubular effect is not fully elucidated. It is known that Dip inhibits the
      activity of the P-glycoprotein (Pgp) multidrug resistance protein 1 (MDR1)
      expressed on the apical membrane of renal proximal tubular cells where the Na-Pi
      cotransporter (NPT2) is also expressed. We hypothesized that Dip could increase
      renal Pi reabsorption by inhibiting Pgp activity. METHODS: To test this
      hypothesis, the effects of Dip, verapamil (Ver), and cyclosporine A (CsA), three
      unrelated Pgp inhibitors, were studied on the renal Pi reabsorption in rats.
      RESULTS: All three drugs decreased the fractional excretion of Pi (FE(Pi)) in a
      dose-dependent manner within one hour after beginning the drug infusion, without
      altering the glomerular filtration rate or serum parathyroid hormone
      concentration. Sodium-dependent Pi uptake but not Na-glucose transport was
      increased in brush-border membrane vesicles (BBMVs) when comparing treated with
      untreated rats. Western blot analysis showed that NPT2 protein was increased in
      BBMVs from treated rats. Dip and Ver had no effect when applied directly to BBMVs
      prepared from untreated rats. Pretreatment of rats with colchicine prevented the
      effects of Dip on the FE(Pi) and NPT2 expression in brush-border membranes.
      CONCLUSIONS: Our results suggest that inhibition of Pgp in the proximal tubule
      increases Pi uptake and NPT2 translocation to the apical membrane.

PMID- 11532102
TI  - Impaired endothelial function in isolated human uremic resistance arteries.
AB  - BACKGROUND: Patients with chronic renal failure (CRF) face a markedly increased
      risk of cardiovascular death. CRF is frequently complicated by hypertension and
      changes in both the heart (left ventricular hypertrophy) and the vasculature
      (endothelial dysfunction and accelerated atherosclerosis). The mechanisms
      underlying changes in vascular function and specifically endothelial dysfunction
      are unclear. This present study therefore examined subcutaneous resistance artery
      function in vitro, comparing adult uremic patients and controls using wire
      myography. METHODS: Subcutaneous fat biopsies were obtained from 12 patients with
      CRF (median serum creatinine 735 micromol/L) at the time of renal transplantation
      or peritoneal dialysis catheter insertion, and from eight controls without renal
      disease at the time of abdominal surgery. Resistance arteries were mounted on a
      wire myograph. Their contractile ability was tested with high potassium
      depolarization, and endothelial integrity was tested by relaxation to
      acetylcholine. Cumulative concentration-response curves were then constructed for
      norepinephrine, endothelin-1, acetylcholine, and sodium nitroprusside (SNP).
      RESULTS: Following preconstriction with norepinephrine, vessels from uremic
      patients vasodilated less well to acetylcholine compared with vessels from
      controls [maximum % relaxation 77% (range 41, 97) vs. 98% (78, 100), P < 0.001].
      The vasodilation to SNP was similar [95% (63, 100) vs. 94% (71, 100), P = 0.751].
      There was a trend toward increased maximum pressure (kPa) achieved with both
      norepinephrine and endothelin-1 in vessels from uremic patients, and the
      contractions to both of these agents were more prolonged in the uremic vessels.
      CONCLUSIONS: The pattern of normal vasodilation to SNP but reduced vasodilation
      to acetylcholine is consistent with endothelial dysfunction due to impaired
      nitric oxide (NO) production in uremic vessels. Similar results have been
      demonstrated in vivo in uremia, one suggested mechanism being accumulation of
      endogenous inhibitors of NO synthase such as asymmetric dimethylarginine (ADMA).
      This in vitro study suggests that a short-lived circulating factor is not
      entirely responsible and that there may be an inherent abnormality in endothelial
      function in uremia, although the exact pathophysiology remains unclear.
      Endothelial dysfunction may predispose the patient to accelerated atherosclerosis
      and may be involved in the pathogenesis of hypertension in end-stage renal
      failure.

PMID- 11532103
TI  - Enhanced nitric oxide inactivation in aortic coarctation-induced hypertension.
AB  - BACKGROUND: Abdominal aortic coarctation above the renal arteries leads to severe
      hypertension (HTN) above the stenotic site. We have recently shown marked up
      regulations of endothelial nitric oxide synthase (eNOS) in heart and thoracic
      aorta and of neuronal NOS (nNOS) in the brain of rats with severe aortic
      coarctation above the renal arteries. We hypothesize that the presence of severe
      regional HTN in the face of marked up-regulation of NO system may be partly due
      to enhanced NO inactivation by reactive oxygen species (ROS) leading to
      functional NO deficiency. METHODS: Tissue nitrotyrosine (which is the footprint
      of NO interaction with ROS) was determined by Western blot in sham-operated
      control and aortic-banded (above renal arteries) rats three weeks
      postoperatively. Intra-arterial pressure and tissue nitrotyrosine (Western blot)
      were measured. RESULTS: The banded group showed a marked rise in arterial
      pressure measured directly through a carotid cannula (203 +/- 9 vs. 131 +/- 2 mm
      Hg, P < 0.01). Compared with the sham-operated controls, the banded animals
      exhibited significant increases in nitrotyrosine abundance in the heart, brain,
      and the aorta segment above the stricture. In contrast, nitrotyrosine abundance
      was unchanged in the abdominal aorta segment below the stricture wherein blood
      pressure was not elevated. CONCLUSION: Coarctation-induced HTN is associated with
      increased nitrotyrosine abundance in all tissues exposed to high arterial
      pressure, denoting enhanced ROS-mediated inactivation and sequestration of NO in
      these sites. This can, in part, account for severe regional HTN in this model.
      The normality of nitrotyrosine abundance in the abdominal aorta wherein blood
      pressure is not elevated points to the role of baromechanical factors as opposed
      to circulating humoral factors that were necessarily similar in both segments.

PMID- 11532104
TI  - Albumin restores lysophosphatidylcholine-induced inhibition of vasodilation in
      rat aorta.
AB  - BACKGROUND: Impairment of vasodilation by oxidized low-density lipoprotein has
      been attributed to lysophosphatidylcholine (LPC). Albumin avidly binds LPC.
      Therefore, hypoalbuminemia may directly impair vasodilation and thus contribute
      to increased risk of atherosclerosis in nephrotic syndrome. The addition of
      albumin reduces LPC in erythrocytes and endothelial cells. We hypothesized that
      the addition of albumin will salvage vasodilation in aortic rings previously
      exposed to LPC. LPC increases superoxide production and disturbs L-arginine
      availability. Therefore, we also decreased superoxide with a superoxide dismutase
      mimic, MnCl(2), and supplemented L-arginine in an attempt to restore
      vasodilation. METHODS: Rat aorta rings, which had been incubated with various
      concentrations of LPC and human serum albumin (HSA), were mounted in organ
      chambers. Relaxation was studied with acetylcholine (0.01 to 100 micromol/L)
      after precontraction with phenylephrine (CON, 0.3 micromol/L; LPC, 0.03
      micromol/L). In some studies MnCl(2) or L-arginine was added to the organ
      chamber. RESULTS: LPC had time- and dose-dependent inhibitory effects on
      acetylcholine-mediated vasodilation, but no effect on nitroprusside-mediated
      vasodilation. Preincubation with albumin (50 or 6 g/L) could protect vasodilation
      against very high levels of LPC. After preincubation with LPC, the addition of
      albumin to the incubation salvaged vasodilation. Albumin was more effective after
      short LPC incubation. MnCl(2) had no specific effect on the LPC-mediated
      disturbance in vasodilation. L-arginine completely salvaged vasodilation at low
      concentrations of LPC. However, even high concentrations of L-arginine (1 mmol/L)
      could not improve vasodilation at LPC levels at which vasodilation was restored
      by albumin. CONCLUSIONS: LPC affects several pathways that inhibit vasodilation,
      all of which are salvaged by addition of albumin.

PMID- 11532105
TI  - Reduction of oxaluria after an oral course of lactic acid bacteria at high
      concentration.
AB  - BACKGROUND: Hyperoxaluria is a major risk factor for renal stones, and in most
      cases, it appears to be sustained by increased dietary load or increased
      intestinal absorption. Previous studies have shown that components of the
      endogenous digestive microflora, in particular Oxalobacter formigenes, utilize
      oxalate in the gut, thus limiting its absorption. We tested the hypothesis of
      whether oxaluria can be reduced by means of reducing intestinal absorption
      through feeding a mixture of freeze-dried lactic acid bacteria. METHODS: Six
      patients with idiopathic calcium-oxalate urolithiasis and mild hyperoxaluria (>40
      mg/24 h) received daily a mixture containing 8 x 10(11) freeze-dried lactic acid
      bacteria (L. acidophilus, L. plantarum, L. brevis, S. thermophilus, B. infantis)
      for four weeks. The 24-hour urinary excretion of oxalate was determined at the
      end of the study period and then one month after ending the treatment. The
      ability of bacteria to degrade oxalate and grow in oxalate-containing media, and
      the gene expression of Ox1T, an enzyme that catalyzes the transmembrane exchange
      of oxalate, also were investigated. RESULTS: The treatment resulted in a great
      reduction of the 24-hour excretion of oxalate in all six patients enrolled. Mean
      levels +/- SD were 33.5 +/- 15.9 mg/24 h at the end of the study period and 28.3
      +/- 14.6 mg/24 h one month after treatment was interrupted compared with baseline
      values of 55.5 +/- 19.6 mg/24 h (P < 0.05). The treatment was associated with a
      strong reduction of the fecal excretion of oxalate in the two patients tested.
      Two bacterial strains among those used for the treatment (L. acidophilus and S.
      thermophilus) proved in vitro to degrade oxalate effectively, but their growth
      was somewhat inhibited by oxalate. One strain (B. infantis) showed a quite good
      degrading activity and grew rapidly in the oxalate-containing medium. L.
      plantarum and L. brevis showed a modest ability to degrade oxalate even though
      they grew significantly in oxalate-containing medium. No strain expressed the
      Ox1T gene. CONCLUSIONS: The urinary excretion of oxalate, a major risk factor for
      renal stone formation and growth in patients with idiopathic calcium-oxalate
      urolithiasis, can be greatly reduced with treatment using a high concentration of
      freeze-dried lactic acid bacteria. We postulate that the biological manipulation
      of the endogenous digestive microflora can be a novel approach for the prevention
      of urinary stone formation.

PMID- 11532106
TI  - An MTHFR variant, homocysteine, and cardiovascular comorbidity in renal disease.
AB  - BACKGROUND: It is unclear whether total serum homocysteine (tHcy) and the C677T
      mutation of methylenetetrahydrofolate reductase (MTHFR) are associated with
      cardiovascular disease (CVD) in patients with end-stage renal disease (ESRD).
      METHODS: A cross-sectional sample of 459 patients with ESRD on chronic dialysis
      was assessed to determine whether tHcy and the C677T mutation are associated with
      CVD prevalence in multiple logistic regression. As CVD mortality is high, we
      examined the relationship between homozygosity and duration of dialysis. RESULTS:
      Mean tHcy was higher in patients without a history of CVD (35.2 micromol/L vs.
      30.4 micromol/L, P = 0.02). In multivariate models, CVD was negatively associated
      with tHcy and positively associated with TT genotype, male gender, and body mass
      index. Mean tHcy levels were higher among those with the TT genotype compared
      with those with the CC genotype when adjusted for age, folate, creatinine, and
      albumin (37.9 micromol/L vs. 31.9 micromol/L, P = 0.005). Among whites, the
      prevalence of the TT genotype was higher in those having undergone less than one
      year of dialysis (P = 0.002). CONCLUSIONS: The C677T genotype of MTHFR is
      associated with CVD in ESRD and may be a more meaningful marker than tHcy for
      abnormal homocysteine metabolism in ESRD. Prospective data from ongoing clinical
      trials are needed to improve our understanding of these findings. Screening for
      this polymorphism may help guide prevention measures.

PMID- 11532107
TI  - The Marmara earthquake: epidemiological analysis of the victims with
      nephrological problems.
AB  - BACKGROUND: Crush syndrome resulting from earthquakes is a major cause of
      morbidity and mortality, as seen during the catastrophic Marmara earthquake that
      struck Northwestern Turkey in August 1999. This report analyzes the
      epidemiological characteristics of the crush syndrome victims of this disaster.
      METHODS: In order to analyze the nephrological problems caused by this
      earthquake, questionnaires were prepared within the first week of the disaster
      and sent to 35 reference hospitals that treated the victims. Data obtained by
      these questionnaires are the subject of this report. RESULTS: Of the 5302
      hospitalized patients in reference hospitals, 639 (12.0%) suffered from
      nephrological problems, and 477 (9.0%) needed dialysis support. Considering the
      patients with renal problems, there was not any significant difference in gender;
      however, the incidence of children younger than 10 years and the older population
      (older than 60 years of age) was significantly lower as compared with the
      resident population of the affected area (P < 0.001). Nonsurvivors were older
      (34.5 +/- 16.1 years) than survivors (31.2 +/- 14.4 years, P = 0.048), while no
      deaths were recorded under the age of 10. Most patients (70.1%) were admitted
      within the first three days after the earthquake, and the mortality rate among
      these victims was higher (17.7%) as compared with victims admitted thereafter
      (10.0%, P = 0.016). The average time period under the rubble was 11.7 +/- 14.3
      hours, which was not significantly different between survivors and nonsurvivors,
      while the victims who required dialysis support spent shorter durations under the
      rubble, as compared with the ones who were not dialyzed at all (10.3 +/- 9.5 vs.
      15.9 +/- 23.1 hours, P < 0.001). CONCLUSION: Victims of catastrophic earthquakes
      are characterized by a high incidence of renal problems and the need for dialysis
      support. The incidence of nephrological problems is lower in children, while the
      period of time under the rubble is not a prognostic indicator of survival.

PMID- 11532108
TI  - Angiotensin-converting enzyme (ACE) I/D genotype and renal ACE gene expression.
AB  - BACKGROUND: The angiotensin-converting enzyme (ACE) I/D genotype affects serum
      ACE levels and the onset and progression of renal disease, but little is known
      about the mechanism. We investigated a possible association between the ACE I/D
      genotype and renal ACE mRNA levels in healthy subjects. METHODS: Renal biopsy
      samples were obtained from 50 healthy kidney donors. The ACE I/D genotype was
      determined by polymerase chain reaction (PCR). Renal ACE mRNA quantification was
      performed by competitive RNA-PCR. In situ hybridization (ISH) for ACE mRNA on
      renal biopsy specimens was also performed. RESULTS: The number of ACE transcripts
      in 100 ng of total RNA was significantly (P < 0.01) lower in subjects with II
      genotype (5.6 +/- 5.3 x 10(5), N = 20) compared with those with the ID (17.9 +/-
      13.6 x 10(5), N = 23) or the DD genotype (36.9 +/- 14.6 x 10(5), N = 7) in
      healthy donors. The ISH studies showed that both tubular and glomerular ACE mRNA
      expressions were weak in subjects with the II genotype, intermediate in subjects
      with ID genotype, and strong in subjects with DD genotype. CONCLUSIONS: It is
      suggested that renal ACE gene expression is associated with the ACE I/D genotype
      in healthy Japanese subjects.

PMID- 11532109
TI  - Proteinuria as a modifiable risk factor for the progression of non-diabetic renal
      disease.
AB  - BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors reduce urine protein
      excretion and slow the progression of renal disease. The beneficial effect in
      slowing the progression of renal disease is greater in patients with higher urine
      protein excretion at the onset of treatment. We hypothesized that the greater
      beneficial effect of ACE inhibitors on the progression of renal disease in
      patients with higher baseline levels of proteinuria is due to their greater
      antiproteinuric effect in these patients. METHODS: Data were analyzed from 1860
      patients enrolled in 11 randomized controlled trials comparing the effect of
      antihypertensive regimens, including ACE inhibitors to regimens not including ACE
      inhibitors on the progression of non-diabetic renal disease. Multivariable linear
      regression analysis was used to assess the relationship between the level of
      proteinuria at baseline and changes in urine protein excretion during follow-up.
      The Cox proportional hazards analysis was used to assess the relationship between
      changes in urine protein excretion during follow-up and the effect of ACE
      inhibitors on the time to doubling of baseline serum creatinine values or onset
      of end-stage renal disease. RESULTS: Mean (median) baseline urine protein
      excretion was 1.8 (0.94) g/day. Patients with higher baseline urine protein
      excretion values had a greater reduction in proteinuria during the follow-up in
      association with treatment with ACE inhibitors and in association with lowering
      systolic and diastolic blood pressures (interaction P < 0.001 for all). A higher
      level of urine protein excretion during follow-up (baseline minus change) was
      associated with a greater risk of progression [relative risk 5.56 (3.87 to 7.98)
      for each 1.0 g/day higher protein excretion]. After controlling for the current
      level of urine protein excretion, the beneficial effect of ACE inhibitors
      remained significant [relative risk for ACE inhibitors vs. control was 0.66 (0.52
      to 0.83)], but there was no significant interaction between the beneficial effect
      of ACE inhibitors and the baseline level of urine protein excretion. CONCLUSIONS:
      The antiproteinuric effects of ACE inhibitors and lowering blood pressure are
      greater in patients with a higher baseline urine protein excretion. The greater
      beneficial effect of ACE inhibitors on renal disease progression in patients with
      higher baseline proteinuria can be explained by their greater antiproteinuric
      effects in these patients. The current level of urine protein excretion is a
      modifiable risk factor for the progression of non-diabetic renal disease. ACE
      inhibitors provide greater beneficial effect at all levels of current urine
      protein excretion.

PMID- 11532110
TI  - A family-based study of metabolic phenotypes in calcium urolithiasis.
AB  - BACKGROUND: A family history increases the risk of kidney stone passage
      independent of dietary risk factors. However, the metabolic basis for familial
      aggregation of urolithiasis is unknown. METHODS: We evaluated metabolic risk
      factors in families with at least two sibs with a history of calcium stones. Sibs
      underwent outpatient evaluations simultaneously, including 24-hour urine
      collection and oral calcium loading. Phenotypes were compared between affected
      and unaffected sibs from the same sibship. RESULTS: Eighty-three sibships
      comprising 388 sibs (212 affected sibs, 114 males and 98 females, and 176
      unaffected sibs, 68 males and 108 females) from 71 families were analyzed. Daily
      urine calcium excretion was higher in affected compared with unaffected sibs
      (0.64 +/- 0.33 vs. 0.50 +/- 0.22 mmol Ca(2+)/mmol creatinine, respectively, P <
      10(-5)). This corresponded to absolute values of 7.4 +/- 3.9 and 5.1 +/- 2.3 mmol
      Ca(2+)/day, respectively, for affected and unaffected males, and 5.4 +/- 2.6 and
      4.2 +/- 1.9 mmol Ca(2+)/day, respectively, for affected and unaffected female
      sibs. When analyzed by tertile of onset age of stone passage, the differences in
      urine calcium were only significant in the first two tertiles (with onset age of
      stone passage <35 years). The fasting urine Ca(2+)/creatinine ratio was
      significantly higher in stone formers compared with control sibs (0.46 +/- 0.27
      vs. 0.40 +/- 0.27, P = 0.04), as was the postcalcium load Ca(2+)/creatinine ratio
      (0.57 +/- 0.46 vs. 0.43 +/- 0.41, respectively, P = 0.02). Body mass index was
      marginally significantly higher in stone forming sibs (P = 0.04). Other urine
      phenotypes, including oxalate, phosphate, magnesium, citrate, urate, sodium,
      ammonium, and volume, were not associated with stone passage. CONCLUSION:
      Increased urine calcium excretion is the only phenotype associated with a kidney
      stone formation in these French-Canadian families.

PMID- 11532111
TI  - Risk factors for post-transplant tuberculosis.
AB  - BACKGROUND: Post-transplant tuberculosis (post-TxTB) occurs in 12 to 20% of
      patients in India and results in the death of 20 to 25% of those patients.
      Prospective studies on post-TxTB are few. METHODS: Renal allograft recipients
      were studied prospectively for 3.1 (0 to 13.9) median (range) years for
      incidence, manifestations, risk factors, and prognosis for post-TxTB. Kaplan
      Meier analysis was used to study the survival rates. The extended Cox
      proportional model for time-dependent covariates was used to measure the risk
      factors when the hazard was nonuniform. RESULTS: Of the 1414 patients considered
      for inclusion, multiple-transplant subjects (N = 37) and patients who developed
      pre-transplant TB (pre-TxTB; N = 126) were excluded from the study. The
      prevalence of post-TxTB was 13.3% (N = 166). The risk of post-TxTB when on
      cyclosporine (CsA) therapy was 2.5 (P = 0.0311) and 1.9 (P = 0.0430) times at <
      or =6 and < or =12 months, respectively, compared with patients on prednisolone
      plus azathioprine (PRED + AZA). The risk of post-TxTB in the presence of diabetes
      mellitus, chronic liver disease, and other co-existing infections [including deep
      mycoses, cytomegalovirus (CMV), Pneumocystis carinii pneumonia (PCP), nocardia]
      was 2.2 (P = 0.0011), 1.7 (P = 0.0010) and 2.4 (P < 0.0001) times, respectively.
      Of the 166 patients with post-TxTB, 53 patients died, and of those deaths, 17
      (32%) were due to post-TxTB; 11 (65%) of the 17 had co-existing infections. The
      factors associated with death were HLA mismatches, PRED + AZA immunosuppression,
      pre- and post-TxTB, diabetes mellitus, post-transplant diabetes (PTDM), and other
      co-existing infections. The extended Cox model for death as the outcome variable
      showed the following to be significant risk factors: post-TxTB> 2 years (P =
      0.0036), chronic liver disease> 6 years (P = 0.0457), PTDM> 5 years (P = 0.0729),
      diabetes mellitus (P = 0.0091), human lymphocyte antigen match < or =1 antigen (P
      = 0.0134), two to three antigens (P = 0.0448), and the presence of other co
      existing infections (P < 0.0001). CONCLUSIONS: Cyclosporine therapy is associated
      with early post-TxTB. Diabetes mellitus and chronic liver disease are risk
      factors for post-TxTB. The occurrence of both pre-TxTB and post-TxTB (>2 years)
      along with hyperglycemia, liver disease, and other co-existing infections are
      important risk factors for death.

PMID- 11532112
TI  - A randomized clinical trial of continuous versus intermittent dialysis for acute
      renal failure.
AB  - BACKGROUND: Acute renal failure (ARF) requiring dialysis in critically ill
      patients is associated with an in-hospital mortality rate of 50 to 80%. The
      worldwide standard for renal replacement therapy is intermittent hemodialysis
      (IHD). Continuous hemodialysis and hemofiltration techniques have recently
      emerged as alternative modalities. These two therapies have not been directly
      compared. METHODS: A multicenter, randomized, controlled trial was conducted
      comparing two dialysis modalities (IHD vs. continuous hemodiafiltration) for the
      treatment of ARF in the intensive care unit (ICU). One hundred sixty-six patients
      were randomized. Principal outcome measures were ICU and hospital mortality,
      length of stay, and recovery of renal function. RESULTS: Using intention-to-treat
      analysis, the overall ICU and in-hospital mortalities were 50.6 and 56.6%,
      respectively. Continuous therapy was associated with an increase in ICU (59.5 vs.
      41.5%, P < 0.02) and in-hospital (65.5 vs. 47.6%, P < 0.02) mortality relative to
      intermittent dialysis. Median ICU length of stay from the time of nephrology
      consultation was 16.5 days, and complete recovery of renal function was observed
      in 34.9% of patients, with no significant group differences. Despite
      randomization, there were significant differences between the groups in several
      covariates independently associated with mortality, including gender, hepatic
      failure, APACHE II and III scores, and the number of failed organ systems, in
      each instance biased in favor of the intermittent dialysis group. Using logistic
      regression to adjust for the imbalances in group assignment, the odds of death
      associated with continuous therapy was 1.3 (95% CI, 0.6 to 2.7, P = NS). A
      detailed investigation of the randomization process failed to explain the marked
      differences in patient assignment. CONCLUSIONS: A randomized controlled trial of
      alternative dialysis modalities in ARF is feasible. Despite the potential
      advantages of continuous techniques, this study provides no evidence of a
      survival benefit of continuous hemodiafiltration compared with IHD. This study
      did not control for other major clinical decisions or other supportive management
      strategies that are widely variable (for example, nutrition support, hemodynamic
      support, timing of initiation, and dose of dialysis) and might materially
      influence outcomes in ARF. Standardization of several aspects of care or
      extremely large sample sizes will be required to answer optimally the questions
      originally posed by this investigation.

PMID- 11532113
TI  - Vascular access blood flow monitoring reduces access morbidity and costs.
AB  - BACKGROUND: Vascular access morbidity results in suboptimal patient outcomes and
      costs more than $8000 per patient-year at risk, representing approximately 15% of
      total Medicare expenditures for ESRD patients annually. In recent years, the rate
      of access thrombosis has improved following the advent of vascular access blood
      flow monitoring (VABFM) programs to identify and treat stenosis prior to
      thrombosis. To define further both the clinical and financial impact of such
      programs, we used the ultrasound dilution method to study the effects of VABFM on
      thrombosis-related morbid events and associated costs, compared with both dynamic
      venous pressure monitoring (DVPM) and no monitoring (NM) in arteriovenous
      fistulas (AVF) and grafts. METHODS: A total of 132 chronic hemodialysis patients
      were followed prospectively for three consecutive study phases (I, 11 months of
      NM; II, 12 months of DVPM; III, 10 months of VABFM). All vascular access-related
      information (thrombosis rate, hospitalization, angiogram, angioplasty, access
      surgery, thrombectomy, catheter placement, missed treatments) was collected
      during the three study periods. RESULTS: During the three study phases, graft
      thrombosis rate was reduced from 0.71 (phase I), to 0.67 (phase II), to 0.16
      (phase III) events per patient-year at risk (P < 0.001 phase III vs. phases I and
      II). Similarly, hospital days, missed treatments, and catheter use related to
      thrombotic events were significantly reduced during phase III compared to phases
      I and II. Hospital days related to vascular access morbidity and adjusted for
      patient-year at risk were 1.8, 1.6, and 0.4 and missed dialysis treatments were
      0.98, 0.86, and 0.26 treatments per patient-year at risk for phases I, II, and
      III, respectively (P < 0.001 for phase III vs. phases I and II). Catheter use was
      also significantly reduced during phases II and III, from 0.29 (phase I) to 0.17
      and further to 0.07 catheters per patient-year at risk, respectively (P < 0.05
      for phase III vs. phase I). Percutaneous angioplasty procedures increased during
      phases II and III from 0.09 to 0.32 to 0.54 procedures per patient-year at risk
      for phases I, II, and III, respectively (P < 0.01 for phase III vs. phase I).
      When the total cost of treatment for thrombosis-related events for grafts was
      estimated, it was found that during phase III, the adjusted yearly billed amount
      was reduced by 49% versus phase I and 54% versus phase II to $158,550. Similar
      trends in reduced thrombosis-related morbid events and cost were observed for
      AVFs. CONCLUSIONS: VABFM for early detection of vascular access malfunction
      coupled with preventive intervention reduces thrombosis rates in both
      polytetrafluoroethylene (PTFE) grafts and native AVFs. While there was a
      significant increase in the number of angioplasties done during the flow
      monitoring phase, the comprehensive cost is markedly reduced due to the decreased
      number of hospitalizations, catheters placed, missed treatments, and surgical
      interventions. Vascular access blood flow monitoring along with preventive
      interventions should be the standard of care in chronic hemodialysis patients.

PMID- 11532114
TI  - Prolonged cold preservation augments vascular injury independent of renal
      transplant immunogenicity and function.
AB  - BACKGROUND: While prolonged cold ischemia has detrimental effects on graft
      survival, the mechanisms remain unclear. We tested whether or not cold
      preservation enhances intragraft inflammatory responses and vascular injury.
      METHODS: Rat renal grafts were cold preserved in University of Wisconsin solution
      for 2, 4, 6, 12, 24, and 48 hours, and then transplanted into syngeneic
      recipients and harvested after 24 hours. Frozen sections were examined
      histologically and stained for vascular cellular adhesion molecule-1 (VCAM-1),
      platelet-endothelial cell adhesion molecule-1 (PECAM-1), major histocompatibility
      complex (MHC) class II, tissue factor, leukocyte function associated molecule-1
      (LFA-1), very late antigen-4 (VLA-4), as well as for inflammatory cells. RESULTS:
      Function did not differ between isografts preserved for shorter (2 to 6 hours) or
      longer times (12 to 24 hours). Neutrophil influx and that of LFA-1-positive cells
      showed similar increases in all groups. Compared with short preservation groups,
      the long preserved grafts had more VLA-4-positive ED-1+ monocytic infiltrates
      adjacent to vessels expressing VCAM-1 (P < or = 0.001). Increased preservation
      duration had no effect on infiltration with recipient ED-2+ macrophages, MHC
      class II-positive cells, or dendritic cells. Decreased color intensity and
      continuity of PECAM-1 staining indicated loss of endothelial integrity in grafts
      preserved for longer than six hours. Intensity in VCAM-1 staining increased
      progressively in grafts preserved for more than six hours and was localized
      predominantly on the endothelium of elastic vessels. Endothelial cells, vascular
      smooth muscle cells, and monocytes expressed increasingly more tissue factor in
      grafts preserved for more than six hours, revealing enhanced intragraft
      procoagulant capacity. Furthermore, grafts with preservation times of more than
      six hours developed more severe vascular endothelial injury and worse tubular
      necrosis scores (P < or = 0.001) compared with grafts with shorter preservation
      times. CONCLUSIONS: Because of the prominent vascular injury, strategies for
      endothelial protection should be attempted in grafts with long preservation times
      in clinical renal transplantation.

PMID- 11532115
TI  - Evidence for a PTH-independent humoral mechanism in post-transplant
      hypophosphatemia and phosphaturia.
AB  - BACKGROUND: Patients undergoing successful kidney transplantation often manifest
      overt hypophosphatemia associated with exaggerated phosphaturia during the early
      post-transplant period (2 weeks to 3 months). The mechanism for this phenomenon
      has not been fully elucidated. We tested the hypothesis that a circulating serum
      factor [non-parathyroid hormone (non-PTH)], which operates during chronic renal
      failure (CRF) to maintain phosphate (Pi) homeostasis, can increase fractional
      excretion of Pi (FE(PO4)) in normal functioning kidney grafts during the early
      post-transplant period, thereby causing phosphaturia and hypophosphatemia.
      METHODS: Five groups of patients were studied: control subjects (group 1, N =
      16), "early" (2 weeks to 1 month) post-transplant patients (group 2, N = 22),
      "late" (9 to 12 months) post-transplant patients (group 3, N = 14), patients with
      advanced CRF (glomerular filtration rate = 30 to 40 mL/min; group 4, N = 8), and
      patients who suffered from end-stage renal failure and were treated by chronic
      hemodialysis (group 5, N = 14). Group 2 manifested significant hypophosphatemia
      and phosphaturia when compared with groups 1 and 3 (Pi = 0.9 +/- 0.003 mg/dL,
      FE(PO4) = 68+/- 5%, P < 0.0005 vs. groups 1 and 3). Sera were taken from each of
      the five subject groups and applied to the proximal tubular opossum kidney (OK)
      cells. The activity of Na/Pi-type 4 (that is, OK-specific type II transporter)
      was evaluated by measuring Na(+)-dependent (32)Pi flux. The expression of Na/Pi
      type II mRNA and the abundance of Na/Pi protein were determined by Northern and
      Western blot assays, respectively. RESULTS: When compared with sera from groups 1
      and 3, 10% sera taken from groups 2, 4, and 5 (incubated overnight with OK cells)
      inhibited (32)Pi flux by 25 to 30% (P < 0.0003). Both Na/Pi mRNA and the
      expression of Na/Pi protein were markedly augmented under the same conditions (P
      < 0.05 groups 2, 4, and 5 vs. groups 1 and 3). Time-course analysis revealed that
      the up-regulation of Na/Pi protein by sera from groups 2, 4, and 5 was observed
      as early as four hours of incubation, whereas augmented abundance of Na/Pi mRNA
      was only seen after eight hours of incubation. The addition of PTH (1-34) to sera
      from groups 2, 4, and 5 abolished the augmented expression of NaPi protein. We
      labeled OK cell surface membrane proteins with N-hydroxysuccinimide bound to
      biotin (NHS-SS-biotin). Biotinylated transporters incubated with the different
      sera were precipitated by strepavidin and identified by Western blot analysis.
      Cells incubated in sera from group 2 showed increased membrane bound transporter
      when compared with control sera, whereas the intracellular pool of the
      transporter was comparable between the two groups. CONCLUSION: A non-PTH
      circulating serum factor (possibly phosphatonin) that increases FE(PO4) during
      CRF is also responsible for phosphaturia and hypophosphatemia in the early period
      following successful kidney transplantation. The putative factor inactivates
      Na/Pi activity along with inhibition of the transporter trafficking from the cell
      membrane into the cytosol.

PMID- 11532116
TI  - Nitric oxide and Bartter and Gitelman syndromes.

PMID- 11532117
TI  - Glomerular epithelial cell arachidonate metabolism in Shiga toxin hemolytic
      uremic syndrome.

PMID- 11532118
TI  - Depression in dialysis patients: rubidium supplementation before other drugs and
      encouragement?

PMID- 11532120
TI  - Apoptosis in post-streptococcal glomerulonephritis.

PMID- 11532122
TI  - Mutations in the Escherichia coli receptor FepA reveal residues involved in
      ligand binding and transport.
AB  - FepA is the Escherichia coli outer membrane receptor for ferric enterobactin,
      colicin D and colicin B. The transport processes through FepA are energy
      dependent, relying on the periplasmic protein TonB to interact with FepA. Through
      this interaction, TonB tranduces energy derived from the cytoplasmic membrane
      across the periplasmic space to FepA. In this study, random mutagenesis
      strategies were used to define residues of FepA important for its function. Both
      polymerase chain reaction (PCR)-generated random mutations in the N-terminal 180
      amino acids of FepA and spontaneous chromosomal fepA mutations were selected by
      resistance to colicin B. The PCR mutagenesis strategy targeted the N-terminus
      because it forms a plug inside the FepA barrel that is expected to be involved in
      ligand binding, ligand transport, and interaction with TonB. We report the
      characterization of 15 fepA missense mutations that were localized to three
      regions of the FepA receptor. The first region was a stretch of eight amino acids
      referred to as the TonB box. The second region included extracellular loops of
      both the barrel and the plug. A third region formed a cluster near the barrel
      wall around positions 75 and 126 of the plug. These mutations provide initial
      insight into the mechanisms of ligand binding and transport through the FepA
      receptor.

PMID- 11532123
TI  - TgM2AP participates in Toxoplasma gondii invasion of host cells and is tightly
      associated with the adhesive protein TgMIC2.
AB  - Like other members of the medically important phylum Apicomplexa, Toxoplasma
      gondii is an obligate intracellular parasite that secretes several classes of
      proteins involved in the active invasion of target host cells. Proteins in apical
      secretory organelles known as micronemes have been strongly implicated in
      parasite attachment to host cells. TgMIC2 is a microneme protein with multiple
      adhesive domains that bind target cells and is mobilized onto the parasite
      surface during parasite attachment. Here, we describe a novel parasite protein,
      TgM2AP, which is physically associated with TgMIC2. TgM2AP complexes with TgMIC2
      within 15 min of synthesis and remains associated with TgMIC2 in the micronemes,
      on the parasite surface during invasion and in the culture medium after release
      from the parasite plasma membrane. TgM2AP is proteolytically processed initially
      when its propeptide is removed during transit through the golgi and later while
      it occupies the parasite surface after discharge from the micronemes. We show
      that TgM2AP is a member of a protein family expressed by coccidian parasites
      including Neospora caninum and Eimeria tenella. This phylogenic conservation and
      association with a key adhesive protein suggest that TgM2AP is a fundamental
      component of the T. gondii invasion machinery.

PMID- 11532124
TI  - Role of the nucleoid-associated protein Fis in the regulation of virulence
      properties of enteropathogenic Escherichia coli.
AB  - Virulence gene expression in enteropathogenic Escherichia coli (EPEC) is governed
      by a combination of environmental factors and virulence regulators. These factors
      control the expression of the bundle-forming pili (BFP), intimin, the type III
      secretion apparatus and the secreted proteins EspA, EspB, EspD and Tir.
      Expression of the bfp genes occurs for a short period in early exponential phase
      during growth in tissue culture medium. The nucleoid-associated regulator
      protein, Fis, is also expressed transiently during this period. To determine
      whether Fis was responsible for the growth phase-dependent expression of bfp, fis
      was deleted from the EPEC strain E2348/69S. Paradoxically, the Delta fis mutant
      retained the ability to colonize HEp-2 cells in a characteristic localized
      adherence pattern, and Fis was found negatively to regulate the expression of
      BFP. However, the Delta fis mutant failed to induce the accretion of filamentous
      actin, which is associated with attaching and effacing lesions. Using a
      combination of Western blotting and a novel multiplex primer extension assay
      (MPEA), we showed that, although the expression of intimin and Tir was not
      affected, transcription of the LEE4 operon encoding espADB and the virulence
      activator, Ler, were found to be Fis dependent.

PMID- 11532125
TI  - De novo formation of focal complex-like structures in host cells by invading
      Streptococci.
AB  - Group A streptococcus (GAS) induces its own entry into eukaryotic cells in vitro
      and in vivo. Fibronectin (Fn) bound to protein F1, a GAS surface protein, acts as
      a bridge connecting the bacterium to host cell integrins. This triggers
      clustering of integrins, which acquire a polar pattern of distribution similar to
      that of protein F1 on the GAS surface. A unique and transient adhesion complex is
      formed at the site of GAS entry, which does not contain alpha-actinin. Vinculin
      is recruited to the site of GAS entry but is not required for uptake. The
      invading GAS recruits focal adhesion kinase (FAK), which is required for uptake
      and is tyrosine phosphorylated. The Src kinases, Src, Yes and Fyn, enhance the
      efficiency of GAS uptake but are not absolutely required for GAS entry. In
      addition, Rac and Cdc42, but not Rho, are required for the entry process. We
      suggest a model in which integrin engagement by Fn-occupied protein F1 triggers
      two independent signalling pathways. One is initiated by FAK recruitment and
      tyrosine phosphorylation, whereas the other is initiated by the recruitment and
      activation of Rac. The two pathways subsequently converge to trigger actin
      rearrangement leading to bacterial uptake.

PMID- 11532126
TI  - An ancient player unmasked: T4 rI encodes a t-specific antiholin.
AB  - Phage T4 effects lysis by its holin T and its endolysin E. Lysis is inhibited
      (LIN) if the infected cell is subjected to secondary infections by T4 phage
      particles. The T4 rI gene is required for LIN in all hosts tested. Here, we show
      that a cloned rI gene can impose a T-specific LIN on T-mediated lysis in the
      context of the phage lambda infective cycle, in the absence of other T4 genes and
      without secondary infection by T4. Moreover, it is shown that the T holin
      accumulates in the membrane during LIN, forming SDS-resistant oligomers. We show
      by cross-linking experiments that a T-RI heterodimer is formed during LIN,
      demonstrating that RI belongs to the functional class of antiholins, such as the
      S107 protein of lambda, which heterodimerizes with its cognate holin, S105.
      Finally, we show that the addition of Ni(2+) ions to the medium can block lysis
      by a T protein hexahistidine-tagged at its C-terminus, suggesting that liganding
      of the periplasmic domain is sufficient to impose lysis inhibition. The results
      are discussed in terms of a model in which the LIN-inducing signal of the
      secondary infecting phage influences a conformational equilibrium assumed by RI
      in the periplasm.

PMID- 11532127
TI  - The operator-early promoter regions of Shiga-toxin bearing phage H-19B.
AB  - Genes (stx) encoding Shiga toxins (Stx), major virulence factors in some
      pathogenic strains of Escherichia coli (STEC), are located in prophages of the
      lambda family. Agents that induce prophages lead to high levels of Stx,
      suggesting a role for the prophage in stx expression. Activation of the phage
      regulatory cascade has been shown to contribute to Stx production and release.
      Therefore, repressor-operator interactions that maintain prophage repression
      appear important in regulating expression of a major bacterial virulence factor.
      To determine if the operators of an stx-bearing phage have distinctive features,
      we characterized the operator regions of H-19B, a lambdoid phage carrying stx1
      genes. H-19B mutants that grow in the presence of repressor (classically called
      virulent mutants) were selected and the mutations definitively identified the
      operators. The H-19B operators, as those in other lambdoid phages, comprise
      variations of an inverted repeat. Four repeats were identified in O(R) rather
      than the three found in each of the operators of other lambdoid phages. Primer
      extensions identified the transcription start sites of P(R) and P(RM), the two
      promoters in O(R) regulated by repressor.

PMID- 11532128
TI  - Glycosylation of a Streptomyces coelicolor A3(2) cell envelope protein is
      required for infection by bacteriophage phi C31.
AB  - Mutants of Streptomyces coelicolor A3(2) J1929 (Delta pglY) were isolated that
      were resistant to the Streptomyces temperate phage phi C31. These strains could
      be transfected with phi C31 DNA, but could not act as infective centres after
      exposure to phage. Thus, it was concluded that infection was blocked at the
      adsorption/DNA injection step. The mutants fell into three classes. Class I
      mutants were complemented by a gene, SCE87.05, isolated from the cosmid library
      of S. coelicolor A3(2). The product of SCE87.05 had good overall homology to a
      Mycobacterium tuberculosis hypothetical protein and regions with similarity to
      dolichol phosphate-D-mannose:protein O-D-mannosyltransferases. Concanavalin A
      (ConA) inhibited phi C31 infection of S. coelicolor J1929, and this could be
      partially reversed by the addition of the sugar, alpha-D-methyl-pyranoside.
      Moreover, glycosylated proteins from J1929, but not from the class I mutant
      DT1017, were detected using ConA as a probe in Western blots. Class I and II
      mutants were sensitive to phi C31hc, a previously isolated phage exhibiting an
      extended host range phenotype, conferred by h. A phage with the same phenotype,
      phi DT4002, was isolated independently, and a missense mutation was found in a
      putative tail gene. It is proposed that the phi C31 receptor is a cell wall
      glycoprotein, and that the phi C31h mutation compensates for the lack of
      glycosylation of the receptor.

PMID- 11532129
TI  - Identification and characterization of App: an immunogenic autotransporter
      protein of Neisseria meningitidis.
AB  - In a search for immunogenic virulence factors in Neisseria meningitidis, we have
      identified a gene encoding a predicted 160 kDa protein with homology to the
      autotransporter family of proteins. Members of this family are secreted or
      surface exposed and are often associated with virulence in Gram-negative
      bacterial pathogens. We named the gene adhesion and penetration protein (app),
      because of its extensive homology to the hap gene of Haemophilus influenzae. We
      reconstructed the gene with reference to genomic sequence data and cloned and
      expressed the protein in Escherichia coli. Rabbit antiserum raised against
      recombinant App reacted with proteins in all meningococcal isolates examined,
      which represented clonal groups responsible for the majority of meningococcal
      invasive disease. Antibodies to the protein were detected in the sera of patients
      convalescing from meningococcal infection. Purified App had strong stimulating
      activity for T cells isolated from a number of healthy donors and from one
      convalescent patient. We confirmed that App is surface localized, cleaved and
      secreted by N. meningitidis. Importantly, the rabbit anti-App serum killed the
      organism in the presence of complement. Thus, App is conserved among
      meningococci, immunogenic in humans and potentially involved in virulence. It
      therefore merits further investigation as a component of a future multivalent
      vaccine.

PMID- 11532130
TI  - Identification of genes required for excision of CTnDOT, a Bacteroides
      conjugative transposon.
AB  - Integrated self-transmissible elements called conjugative transposons have been
      found in many different bacteria, but little is known about how they excise from
      the chromosome to form the circular intermediate, which is then transferred by
      conjugation. We have now identified a gene, exc, which is required for the
      excision of the Bacteroides conjugative transposon, CTnDOT. The int gene of
      CTnDOT is a member of the lambda integrase family of recombinases, a family that
      also contains the integrase of the Gram-positive conjugative transposon Tn916.
      The exc gene was located 15 kbp from the int gene, which is located at one end of
      the 65 kbp element. The exc gene, together with the regulatory genes, rteA, rteB
      and rteC, were necessary to excise a miniature form of CTnDOT that contained only
      the ends of the element and the int gene. Another open reading frame (ORF) in the
      same operon and upstream of exc, orf3, was not essential for excision and had no
      significant amino acid sequence similarity to any proteins in the databases. The
      deduced amino acid sequence of the CTnDOT Exc protein has significant similarity
      to topoisomerases. A small ORF (orf2) that could encode a small, basic protein
      comparable with lambda and Tn916 excision proteins (Xis) was located immediately
      downstream of the CTnDOT int gene. Although Xis proteins are required for
      excision of lambda and Tn916, orf2 had no effect on excision of the element.
      Excision of the CTnDOT mini-element was not affected by the site in which it was
      integrated, another difference from Tn916. Our results demonstrate that the
      Bacteroides CTnDOT excision system is tightly regulated and appears to be
      different from that of any other known integrated transmissible element,
      including those of some Bacteroides mobilizable transposons that are mobilized by
      CTnDOT.

PMID- 11532131
TI  - Evidence for dual functionality of the operon plnABCD in the regulation of
      bacteriocin production in Lactobacillus plantarum.
AB  - The regulatory operon (plnABCD) involved in bacteriocin production in
      Lactobacillus plantarum C11 encodes four different proteins: a cationic
      prepeptide (PlnA); a histidine protein kinase (PlnB); and two highly homologous
      response regulators (PlnC and PlnD; over 75% sequence similarity). The mature
      product of PlnA, plantaricin A, serves as an extracellular pheromone that induces
      bacteriocin production. The exact roles of plnBCD in bacteriocin production have
      not been established experimentally. A reporter system containing the gusA gene
      fused with the plnA promoter was used to study plnABCD. We demonstrated that the
      plnABCD operon codes for an autoregulatory unit capable of activating its own
      promoter. Deletion analyses, performed in a heterologous expression host to
      define the roles of the individual genes, confirmed that both the inducer gene
      (plnA) and the kinase gene (plnB) are required for autoactivation. Apparently,
      the latter gene encodes a protein that serves as a receptor for the pheromone
      peptide. It was also demonstrated conclusively that the two regulators PlnC and
      PlnD, which have been shown previously to bind specifically to the DNA regulatory
      repeats of the plnA promoter, possess differential activities on the plnA
      promoter, with PlnC being much more active than PlnD. The functions of the
      response regulators were investigated further in the bacteriocin producer strain
      C11 in order to reveal their roles in bacteriocin production. Surprisingly, the
      two response regulators display totally opposite functions: although
      overexpression of plnC activated transcription and bacteriocin production, the
      overexpression of plnD repressed both processes, thus strongly suggesting that
      PlnD plays a role in the downregulation of bacteriocin synthesis. To our
      knowledge, this is the first evidence for a protein involved directly in negative
      regulation of bacteriocin production, and also it was shown for the first time
      that two highly homologous response regulators, with opposite functions, are
      encoded by genes located on the same operon.

PMID- 11532132
TI  - Ectopic transposition of a group II intron in natural bacterial populations.
AB  - Self-splicing group II introns are thought to be the evolutionary progenitors of
      eukaryotic spliceosomal introns. The invasion of novel (ectopic) sites by group
      II introns is considered to be a key mechanism by which spliceosomal introns may
      have become widely dispersed. However, the dynamics of these events in
      populations are unknown. In bacteria, only two group II introns have been shown
      to splice and to be mobile in vivo. One of these introns, RmInt1 from
      Sinorhizobium meliloti, which encodes a protein with no endonuclease domain, has
      been shown to invade the ectopic oxi1 site independently of recombinase. In this
      study, we analysed ectopic transposition of the RmInt1 intron in a natural
      population of S. meliloti. We characterized S. meliloti isolates by polymerase
      chain reaction amplification of a gene, dapB, which is found only on the pRmeGR4b
      plasmid diagnostic of GR4-type strains. The diversity within this specific field
      population of bacteria was analysed by restriction fragment length polymorphism
      using ISRm2011-2 (homing site of RmInt1) and RmInt1 as probes. We found that
      ectopic transposition of RmInt1 to the oxi1 site occurred in this natural
      bacterial population. This ectopic transposition was also the most frequent
      genetic event observed. This work provides further evidence that the ectopic
      transposition of group II introns is an important mechanism for their spread in
      natural bacterial populations.

PMID- 11532133
TI  - The fla gene cluster is involved in the biogenesis of flagella in Halobacterium
      salinarum.
AB  - In this study, a flagella-related protein gene cluster is described for
      Halobacterium salinarum. The fla gene cluster is located upstream of the
      flagellin genes flgB1-3 and oriented in the opposite direction. It consists of
      nine open reading frames (ORFs): htpIX, a member of the halobacterial transducer
      protein gene family, and the genes flaD-K. The genes flaD, E, G, H, I and J share
      high homologies with genes from other Archaea. Interestingly, flaK shows
      similarities to bacterial genes involved in the regulation of flagellar
      synthesis. The ORFs of flaH, flaI and flaK contain sequences coding for
      nucleotide binding sites. Furthermore, flaI contains a motif called the bacterial
      type II secretion protein E signature, indicating a functional relation to
      members of the bacterial pili type IV-type II secretion protein superfamily.
      Reverse transcription-polymerase chain reaction (RT-PCR) analysis revealed that
      the genes flaE to flaK are transcribed into one polycistronic message. In frame
      deletion mutants of flaI were generated by gene replacement. The deletion strain
      lacks motility and belongs to the fla(-) mutant class, indicating that it is
      deficient in flagellar biogenesis. The overall amount of flagellin protein in
      Delta flaI cells is reduced, although transcription of the flagellin genes is
      unaffected. Therefore, the flaI gene product is involved in the biosynthesis,
      transport or assembly of flagella in H. salinarum.

PMID- 11532134
TI  - Identification of a cell wall channel of Streptomyces griseus: the channel
      contains a binding site for streptomycin.
AB  - Cells of the Gram-positive actinomycete Streptomyces griseus were disrupted and
      the cell envelope was subjected to sucrose step-gradient centrifugation. The
      different fractions were analysed for NADH-oxidase activity and the formation of
      ion-permeable channels in lipid bilayers. Highest channel-forming activity and
      highest NADH-oxidase activity were found in different fractions. The cell wall
      fraction contained an ion-permeable channel with a single-channel conductance of
      850 pS in 1 M KCl. The channel-forming protein, with an apparent molecular mass
      of 28 kDa, was purified to homogeneity using fast protein liquid chromatography
      after the extraction of whole cells with detergent. Single-channel experiments
      suggest that the cell wall channel is wide and water-filled. Titration
      experiments with streptomycin produced by S. griseus suggested that the cell wall
      channel binds this antibiotic with a half saturation constant of about 6 mM in 1
      M KCl. The binding of streptomycin was found to be ionic strength dependent and
      the half saturation constant decreased to 60 microM at 0.1 M KCl. The results
      indicate that the 28 kDa protein represents the hydrophilic pathway through the
      cell wall of the Gram-positive bacterium S. griseus.

PMID- 11532135
TI  - Valency conversion in the type 1 fimbrial adhesin of Escherichia coli.
AB  - FimH protein is a lectin-like adhesive subunit of type 1, or mannose-sensitive,
      fimbriae that are found on the surface of most Escherichia coli strains. All
      naturally occurring FimH variants demonstrate a conserved mannotriose-specific
      (i.e. multivalent) binding. Here, we demonstrate that replacement of residues 185
      279 within the FimH pilin domain with a corresponding segment of the type 1C
      fimbrial adhesin FocH leads to a loss of the multivalent mannotriose-specific
      binding property accompanied by the acquisition of a distinct monomannose
      specific (i.e. monovalent) binding capability. Bacteria expressing the monovalent
      hybrid adhesins were capable of binding strongly to uroepithelial tissue culture
      cells and guinea pig erythrocytes. They could not, however, agglutinate yeast or
      bind human buccal cells -- functions readily accomplished by the E. coli
      expressing mannotriose-specific FimH variants. Based on the relative potency of
      inhibiting compounds of different structures, the receptor binding site within
      monovalent FimH-FocH adhesin has an extended structure with an overall
      configuration similar to that within the multivalent FimH of natural origin. The
      monomannose-only specific phenotype could also be invoked by a single point
      mutation, E89K, located within the lectin domain of FimH, but distant from the
      receptor binding site. The structural alterations influence the receptor-binding
      valency of the FimH adhesin via distal effects on the combining pocket, obviously
      by affecting the FimH quaternary structure.

PMID- 11532136
TI  - Role of vicinal cysteine pairs in metalloid sensing by the ArsD As(III)
      responsive repressor.
AB  - ArsD is a 120-residue repressor that regulates expression of the arsRDABC
      arsenical resistance operon of plasmid R773 in Escherichia coli. ArsD is released
      from arsRDABC promoter DNA by binding of the compounds with the metalloids
      As(III) or Sb(III). ArsD has three vicinal cysteine pairs, Cys-12 and Cys-13, Cys
      112 and Cys-113 and Cys-119 and Cys-120. In this study, the role of these three
      cysteine pairs was investigated. Mutation or deletion of Cys-119-Cys-120 had no
      effect on repression or metalloid responsiveness in vivo or in vitro. Mutagenesis
      of either the Cys-12-Cys-13 pair or the Cys-112-Cys-113 pair had no effect on
      repression but produced loss of inducibility, suggesting that both Cys-12-Cys-13
      and Cys-112-Cys-113 may be required for As(III) or Sb(III) responsiveness. Assays
      of binding of wild-type and mutant ArsDs by As(III) affinity chromatography
      showed that each of the three vicinal cysteine pairs is capable of binding
      As(III) independently. The effect of As(III) or Sb(III) on intrinsic protein
      fluorescence was used to examine the properties of individual cysteine pairs. The
      fluorescence of Trp-97 was shown to be quenched by the addition of Sb(III) or
      As(III). The vicinal Cys-112-Cys-113 pair was required for the majority of the
      metalloid-dependent quenching of Trp-97 fluorescence. The data are consistent
      with a model in which Cys-12-Cys-13 and Cys-112-Cys-113 form independent As(III)
      binding sites, both of which are required for in vivo ArsD function.

PMID- 11532137
TI  - PriA mutations that affect PriA-PriC function during replication restart.
AB  - In Escherichia coli, repair and restart of collapsed replication forks is thought
      to be essential for cell growth. The replication restart proteins, PriA, PriB,
      PriC, DnaB, DnaC, DnaG, DnaT and Rep, form redundant pathways that recognize
      repaired replication forks and restart them. Recognition, modulation of specific
      DNA structures and loading of the replicative helicase by the replication restart
      proteins, is likely to be important for replication restart. It has been
      hypothesized that PriB and PriC function with PriA in genetically separate and
      redundant PriA-PriB and PriA-PriC pathways. In this study, the del(priB)302 or
      priC303:kan mutations were used to isolate the PriA-PriB and PriA-PriC pathways
      genetically so that the effects of three priA missense mutations, priA300
      (K230R), priA301 (C479Y) and priA306 (L557P), on these pathways could be
      assessed. In a wild-type background, the three priA mutations had little, if any,
      effect on the phenotypes of UV resistance, basal levels of SOS expression and
      cell viability. In the priB mutant, priA300 and priA301 caused dramatic negative
      changes in the three phenotypes listed above (and others), whereas the third priA
      mutant allele, priA306, showed very little negative effect. In the priC mutant,
      all three priA mutations behaved similarly, producing little, if any, changes in
      phenotypes. We conclude that priA300 and priA301 mostly affect the PriA-PriC
      pathway and do so more than priA306. We suggest that PriA's helicase activity is
      important for the PriA-PriC pathway of replication restart.

PMID- 11532138
TI  - Role of activator site position and a distal UP-element half-site for sigma
      factor selectivity at a CRP/H-NS-activated sigma(s)-dependent promoter in
      Escherichia coli.
AB  - Transcription initiation by the stress-associated sigma(S)-containing RNA
      polymerase holoenzyme (E sigma(S)) in Escherichia coli is often subject to
      complex regulation that involves multiple additional regulators and histone-like
      proteins. csiD is a stationary phase-inducible sigma(S)-dependent gene in E. coli
      that requires activation by cAMP-CRP (bound to a site centred at -68.5
      nucleotides upstream of the transcriptional start site) and is positively
      modulated by the abundant nucleoid-associated proteins H-NS and Lrp. By shifting
      the CRP box to positions between -80.5 and -60.5, we could demonstrate that: (i)
      activation is equally helix phase dependent as at classic class I promoters; (ii)
      E sigma(S) prefers a CRP box location at -68.5/-70.5, whereas E sigma(70) is
      nearly inactive with such an arrangement; and (iii) with the CRP site moved to 
      60.5, transcription can be initiated efficiently by both holoenzymes. The csiD
      promoter region also contains a distal UP-element half-site located downstream of
      the CRP box, as demonstrated by mutational studies, in which this element was
      either eliminated or completed to a full UP-element. The UP-element half-site
      favours E sigma(S)-mediated expression, whereas with the full UP-element, nearly
      wild-type levels of csiD transcription were observed in the absence of sigma(S).
      Finally, we show that the two histone-like proteins, H-NS and Lrp, both act by
      influencing activation by cAMP-CRP, but do so by different mechanisms. In
      particular, H-NS directly or indirectly increases positional stringency for the
      CRP binding site. The implications of these findings with respect to sigma factor
      selectivity, activation mechanisms used by the two holoenzymes and the
      architecture of sigma(S)-dependent promoters are discussed.

PMID- 11532139
TI  - Hyperosmotic stress response and regulation of cell wall integrity in
      Saccharomyces cerevisiae share common functional aspects.
AB  - The osmosensitive phenotype of the hog1 strain is suppressed at elevated
      temperature. Here, we show that the same holds true for the other commonly used
      HOG pathway mutant strains pbs2 and sho1ssk2ssk22, but not for ste11ssk2ssk22.
      Instead, the ste11ssk2ssk2 strain displayed a hyperosmosensitive phenotype at 37
      degrees C. This phenotype is suppressed by overexpression of LRE1, HLR1 and WSC3,
      all genes known to influence cell wall composition. The suppression of the
      temperature-induced hyperosmosensitivity by these genes prompted us to
      investigate the role of STE11 and other HOG pathway components in cellular
      integrity and, indeed, we were able show that HOG pathway mutants display
      sensitivity to cell wall-degrading enzymes. LRE1 and HLR1 were also shown to
      suppress the cell wall phenotypes associated with the HOG pathway mutants. In
      addition, the isolated multicopy suppressor genes suppress temperature-induced
      cell lysis phenotypes of PKC pathway mutants that could be an indication for
      shared targets of the PKC pathway and high-osmolarity response routes.

PMID- 11532140
TI  - Expression of Chlamydia trachomatis genes encoding products required for DNA
      synthesis and cell division during active versus persistent infection.
AB  - During persistent infection, the intracellular bacterial pathogen Chlamydia
      trachomatis is viable but severely attenuates the production of new, infectious
      elementary bodies (EBs). To investigate the reasons for this lack of new EB
      output, we analysed the expression of chlamydial genes encoding products required
      for DNA replication and cell division, using in vitro models of active versus
      persistent infection and synovial tissue samples from patients with chronic
      Chlamydia-associated arthritis. Hep-2 cells were infected with K serovar C.
      trachomatis and harvested at t = 0-48 h post-infection (p.i; active). Human
      monocytes were infected similarly and harvested at t = 1-7 days p.i.
      (persistent). RNA preparations from infected/uninfected cells and patient samples
      were subjected to reverse transcription-polymerase chain reaction (RT-PCR)
      targeting polA, dnaA, mutS and parB mRNA, related to chlamydial DNA
      replication/segregation; these were expressed in infected Hep-2 cells from 11 to
      48 h p.i; ftsK and ftsW, related to cell division, were expressed similarly. Real
      time PCR analyses demonstrated that significant accumulation of chlamydial
      chromosome began at about 12 h p.i. in infected Hep-2 cells. In infected human
      monocytes, polA, dnaA, mutS and parB mRNA were produced from days 1-7 p.i. and
      were weakly expressed in patient samples. Real-time PCR indicated the continuing
      accumulation of chlamydial chromosome during the 7 day monocyte infection,
      although the rate of such accumulation was lower than that occurring during
      active growth. However, transcripts from ftsK and ftsW were detected only at 1
      day p.i. in infected monocytes but not thereafter, and they were absent in all
      patient samples. Thus, genes whose products are required for chlamydial DNA
      replication are expressed during persistence, but transcription of genes whose
      products are required for cytokinesis is severely downregulated. These data
      explain, at least in part, the observed attenuation of new EB production during
      chlamydial persistence.

PMID- 11532141
TI  - Genetic analysis of the chromosome segregation protein Spo0J of Bacillus
      subtilis: evidence for separate domains involved in DNA binding and interactions
      with Soj protein.
AB  - Spo0J and Soj belong to the ParB/ParA family of proteins involved in chromosome
      and plasmid segregation in bacteria. In Bacillus subtilis, Spo0J protein binds to
      several specific sites, parS, located on both sides of the origin of DNA
      replication, oriC, and apparently self-associates to form large discrete foci
      visible by fluorescence microscopy. Soj protein forms large 'patches' probably
      associated with the nucleoid, which can undergo dynamic, co-operative jumping
      from nucleoid to nucleoid in the presence of Spo0J. Patches of Soj protein
      somehow help to bring about the condensation of Spo0J foci. Soj is also a
      negative regulator of transcription. In the absence of Spo0J, Soj is statically
      distributed on each of the nucleoids in the cell and blocks the transcription of
      several sporulation genes. To analyse the functional interaction between Spo0J
      and Soj further, we have constructed and studied a collection of spo0J mutants.
      Most of the mutants completely prevent Spo0J from interacting with DNA. One
      mutation impairs the formation of compact Spo0J foci and simultaneously results
      in loss of Soj movement. We also isolated one spo0J mutant, in which the
      frequency of Soj internucleoid oscillation is highly increased. Both mutations
      affecting the interaction with Soj lie in the N-terminal coding part of spo0J,
      whereas the substitutions affecting DNA binding lie in the mid- to C-terminal
      coding region.

PMID- 11532142
TI  - Genome-wide analysis of the general stress response in Bacillus subtilis.
AB  - Bacteria respond to diverse growth-limiting stresses by producing a large set of
      general stress proteins. In Bacillus subtilis and related Gram-positive
      pathogens, this response is governed by the sigma(B) transcription factor. To
      establish the range of cellular functions associated with the general stress
      response, we compared the transcriptional profiles of wild and mutant strains
      under conditions that induce sigma(B) activity. Macroarrays representing more
      than 3900 annotated reading frames of the B. subtilis genome were hybridized to
      (33)P-labelled cDNA populations derived from (i) wild-type and sigB mutant
      strains that had been subjected to ethanol stress; and (ii) a strain in which
      sigma(B) expression was controlled by an inducible promoter. On the basis of
      their significant sigma(B)-dependent expression in three independent experiments,
      we identified 127 genes as prime candidates for members of the sigma(B) regulon.
      Of these genes, 30 were known previously or inferred to be sigma(B) dependent by
      other means. To assist in the analysis of the 97 new genes, we constructed hidden
      Markov models (HMM) that identified possible sigma(B) recognition sequences
      preceding 21 of them. To test the HMM and to provide an independent validation of
      the hybridization experiments, we mapped the sigma(B)-dependent messages for
      seven representative genes. For all seven, the 5' end of the message lay near
      typical sigma(B) recognition sequences, and these had been predicted correctly by
      the HMM for five of the seven examples. Lastly, all 127 gene products were
      assigned to functional groups by considering their similarity to known proteins.
      Notably, products with a direct protective function were in the minority.
      Instead, the general stress response increased relative message levels for known
      or predicted regulatory proteins, for transporters controlling solute influx and
      efflux, including potential drug efflux pumps, and for products implicated in
      carbon metabolism, envelope function and macromolecular turnover.

PMID- 11532143
TI  - KP4 fungal toxin inhibits growth in Ustilago maydis by blocking calcium uptake.
AB  - KP4 is a virally encoded fungal toxin secreted by the P4 killer strain of
      Ustilago maydis. From our previous structural studies, it seemed unlikely that
      KP4 acts by forming channels in the target cell membrane. Instead, KP4 was
      proposed to act by blocking fungal calcium channels, as KP4 was shown to inhibit
      voltage-gated calcium channels in rat neuronal cells, and its effects on fungal
      cells were abrogated by exogenously added calcium. Here, we extend these studies
      and demonstrate that KP4 acts in a reversible manner on the cell membrane and
      does not kill the cells, but rather inhibits cell division. This action is
      mimicked by EGTA and is abrogated specifically by low concentrations of calcium
      or non-specifically by high ionic strength buffers. We also demonstrate that KP4
      affects (45)Ca uptake in U. maydis. Finally, we show that cAMP and a cAMP
      analogue, N 6,2'-O-dibutyryladenosine 3':5'-cyclic monophosphate, both abrogate
      KP4 effects. These results suggest that KP4 may inhibit cell growth and division
      by blocking calcium-regulated signal transduction pathways.

PMID- 11532144
TI  - Discovery of a haem uptake system in the soil bacterium Bradyrhizobium japonicum.
AB  - In Bradyrhizobium japonicum, the nitrogen-fixing symbiont of soybeans, we have
      identified a haem uptake system, Hmu, that comprises a cluster of nine open
      reading frames. Predicted products of these genes include: HmuR, a TonB-dependent
      haem receptor in the outer membrane; HmuT, a periplasmic haem-binding protein;
      and HmuUV, an ABC transporter in the inner membrane. Furthermore, we identified
      homologues of ExbBD and TonB, that are required for energy transduction from the
      inner to the outer membrane. Mutant analysis and complementation tests indicated
      that HmuR and the ExbBD-TonB system, but not the HmuTUV transporter, are
      essential for haem uptake or haem acquisition from haemoglobin and
      leghaemoglobin. The TonB system seems to be specific for haem uptake as it is
      dispensable for siderophore uptake. Therefore, we propose the existence of a
      second TonB homologue functioning in the uptake of Fe-chelates. When tested on
      soybean host plants, hmuT-hmuR and exbD-tonB mutants exhibited wild-type
      symbiotic properties. Thus, haem uptake is not essential for symbiotic nitrogen
      fixation but it may enable B. japonicum to have access to alternative iron
      sources in its non-symbiotic state. Transcript analysis and expression studies
      with lacZ fusions showed that expression of hmuT and hmuR is induced under low
      iron supply. The same was observed in fur and irr mutant backgrounds although
      maximal induction levels were decreased. We conclude either that both regulators,
      Fur and Irr, independently mediate transcriptional control by iron or that a yet
      unknown iron regulatory system activates gene expression under iron deprivation.
      An A/T-rich cis-acting element, located in the promoter region of the divergently
      transcribed hmuTUV and hmuR genes, is possibly required for this type of iron
      control.

PMID- 11532145
TI  - The Rhizobium leguminosarum tonB gene is required for the uptake of siderophore
      and haem as sources of iron.
AB  - In the N2-fixing bacterium Rhizobium leguminosarum, mutations in a homologue of
      tonB (tonB(Rl)) block the import of vicibactin and haem as iron sources in free
      living bacteria. TonB(Rl) mutants were normal for growth with ferric dicitrate
      and slightly reduced for growth with haemoglobin as sole iron sources. The
      deduced TonB(Rl) product is larger than that of (for example) Escherichia coli,
      on account of an extended N-terminal domain. Transcription of tonB(Rl) was
      enhanced in low-Fe growth conditions; this was not controlled by Fur, nor RpoI,
      an Fe-regulated extracytoplasmic sigma factor. Upstream of tonB(Rl) and
      transcribed divergently is an operon, hmuPSTUV, whose products are homologous to
      ABC transporters involved in haem uptake in pathogenic bacteria. Expression of
      hmuPSTUV was enhanced in low-Fe conditions, and hmu mutants show slightly
      diminished growth on haem as sole Fe source, suggesting that there is more than
      one system for the uptake of this molecule. hmuPSTUV expression appears to be
      from three closely linked promoters. Downstream of hmuPSTUV, a gene that may
      encode an extracytoplasmic sigma factor was identified, but this gene, rpoZ, did
      not affect the transcription of tonB(Rl) or hmuPSTUV. Mutations in tonB(Rl), hmu
      genes and rpoZ did not affect symbiotic N(2) fixation in peas.

PMID- 11532146
TI  - Group A streptococcal phagocytosis resistance is independent of complement factor
      H and factor H-like protein 1 binding.
AB  - Factor H (FH) and factor H-like protein 1 (FHL-1) regulate complement activation
      through the alternative pathway. Several extracellular bacterial pathogens, prime
      targets for the complement system, bind FH and FHL-1, thereby acquiring a
      potential mechanism for minimizing complement deposition on their surface. For
      group A streptococci (GAS), surface-bound antiphagocytic M proteins mediate the
      interaction. To study the role of the FH-FHL-1 interaction for complement
      deposition and opsonophagocytosis of GAS, we first constructed a set of truncated
      M5 protein variants and expressed them on the surface of a homologous M-negative
      GAS strain. Binding experiments with the resulting strains demonstrated that the
      major FH-FHL-1 binding is located in a 42-amino-acid region within the N-terminal
      third of M5. Measurement of bacteria-bound complement factor C3 after incubation
      in plasma showed that the presence of this region had little impact upon
      complement deposition through the alternative pathway. Moreover, streptococci
      expressing M5 proteins lacking the major FH and FHL-1 binding sequence resisted
      phagocytosis in human blood as efficiently as bacteria expressing the wild-type
      protein. Consequently, the data suggest that the binding of the regulators of the
      alternative pathway is of limited importance for GAS phagocytosis resistance.

PMID- 11532147
TI  - A bacterial linear motor: cellular and molecular organization of the contractile
      cytoskeleton of the helical bacterium Spiroplasma melliferum BC3.
AB  - The Mollicutes (Mycoplasma, Acholeplasma, and Spiroplasma) are the smallest,
      simplest and most primitive free-living and self-replicating known cells. These
      bacteria have evolved from Clostridia by regressive evolution and genome
      reduction to the range of 5.8 x 10(5)-2.2 x 10(6) basepairs (bp). Structurally,
      the Mollicutes completely lack cell walls and are enveloped by only a cholesterol
      containing cell membrane. The Mollicutes contain what can be defined as a
      bacterial cytoskeleton. The Spiroplasmas are unique in having a well-defined,
      dynamic, helical cell geometry and a flat, monolayered, membrane-bound
      cytoskeleton, which follows, intracellularly, the shortest helical line on the
      cellular coil. By applying cryo-electron-microscopy to whole cells, isolated
      cytoskeletons and cytoskeletal fibrils and subunits, as well as by selective
      extraction of cellular components, we determined, at a resolution of
      approximately 25 A, the cellular and molecular organization of the cytoskeleton.
      The cytoskeleton is assembled from a 59 kDa protein. The 59 kDa protein, has an
      equivalent sphere diameter of approximately 50 A. Given the approximately 100 A
      axial and lateral spacings in the cytoskeletal ribbons and the near-circular
      shape of the subunit, we suggest that the subunit is a tetramer of 59 kDa
      monomers; the tetramers assemble further into flat fibrils, seven of which form a
      flat, monolayered, well-ordered ribbon. The cytoskeleton may function as a linear
      motor by differential and coordinated length-changes of the fibrils driven by
      conformational changes of the tetrameric subunits, the shape of which changes
      from near circular to elliptical. The cytoskeleton controls both the dynamic
      helical shape and the consequent motility of the cell. A stable cluster of
      proteins co-purifies with the cytoskeleton. These apparent membrane and membrane
      associated proteins may function as anchor proteins.

PMID- 11532148
TI  - Roles of metal ions and hydrogen peroxide in modulating the interaction of the
      Bacillus subtilis PerR peroxide regulon repressor with operator DNA.
AB  - The inducible response to H(2)O(2) stress in Bacillus subtilis is under the
      control of PerR, one of three Fur homologues in this organism. PerR was purified
      in both an inactive, metal-dependent form and an active, metal-containing form as
      determined using DNA-binding assays. Active PerR contains both zinc and iron and
      is designated PerR:Zn,Fe. Added manganous ion competes for binding to the iron
      site and can restore DNA-binding activity to the metal-dependent form of PerR,
      presumably generating PerR:Zn,Mn. The DNA-binding activity of PerR:Zn,Fe is
      eliminated by exposure to H(2)O(2) whereas PerR:Zn,Mn is comparatively resistant.
      DNA-binding activity can be restored by a thiol-reducing agent, suggesting that
      redox-active cysteines are involved in peroxide sensing. Experiments using
      reporter fusions demonstrate that elevated levels of manganese repress PerR
      regulon genes and prevent their full induction by H(2)O(2). In contrast, in cells
      grown with iron supplementation, a PerR-repressed gene is completely derepressed
      by H(2)O(2). These results are consistent with the idea that the intracellular
      form of the PerR metalloprotein, and therefore its hydrogen peroxide sensitivity,
      can be altered by growth conditions.

PMID- 11532149
TI  - The making of a gradient: IcsA (VirG) polarity in Shigella flexneri.
AB  - The generation and maintenance of subcellular organization in bacteria is
      critical for many cell processes and properties, including growth, structural
      integrity and, in pathogens, virulence. Here, we investigate the mechanisms by
      which the virulence protein IcsA (VirG) is distributed on the bacterial surface
      to promote efficient transmission of the bacterium Shigella flexneri from one
      host cell to another. The outer membrane protein IcsA recruits host factors that
      result in actin filament nucleation and, when concentrated at one bacterial pole,
      promote unidirectional actin-based motility of the pathogen. We show here that
      the focused polar gradient of IcsA is generated by its delivery exclusively to
      one pole followed by lateral diffusion through the outer membrane. The resulting
      gradient can be modified by altering the composition of the outer membrane either
      genetically or pharmacologically. The gradient can be reshaped further by the
      action of the protease IcsP (SopA), whose activity we show to be near uniform on
      the bacterial surface. Further, we report polar delivery of IcsA in Escherichia
      coli and Yersinia pseudotuberculosis, suggesting that the mechanism for polar
      delivery of some outer membrane proteins is conserved across species and that the
      virulence function of IcsA capitalizes on a more global mechanism for subcellular
      organization.

PMID- 11532150
TI  - Recombinational repair of chromosomal DNA double-strand breaks generated by a
      restriction endonuclease.
AB  - DNA double-strand break repair can be accomplished by homologous recombination
      when a sister chromatid or a homologous chromosome is available. However, the
      study of sister chromatid double-strand break repair in prokaryotes is
      complicated by the difficulty in targeting a break to only one copy of two
      essentially identical DNA sequences. We have developed a system using the
      Escherichia coli chromosome and the restriction enzyme EcoKI, in which double
      strand breaks can be introduced into only one sister chromatid. We have shown
      that the components of the RecBCD and RecFOR 'pathways' are required for the
      recombinational repair of these breaks. Furthermore, we have shown a requirement
      for SbcCD, the prokaryotic homologue of Rad50/Mre11. This is the first
      demonstration that, like Rad50/Mre11, SbcCD is required for recombination in a
      wild-type cell. Our work suggests that the SbcCD-Rad50/Mre11 family of proteins,
      which have two globular domains separated by a long coiled-coil linker, is
      specifically required for the co-ordination of double-strand break repair
      reactions in which two DNA ends are required to recombine at one target site.

PMID- 11532151
TI  - A chimeric activator of transcription that uses two DNA-binding domains to make
      simultaneous contact with pairs of recognition sites.
AB  - Many well-known transcriptional regulatory proteins are composed of at least two
      independently folding domains and, typically, only one of these is a DNA-binding
      domain. However, some transcriptional regulators have been described that have
      more than one DNA-binding domain. Regulators with a single DNA-binding domain
      often bind co-operatively to the DNA in homotypic or heterotypic combinations,
      and two or more DNA-binding domains of a single regulatory protein can also bind
      co-operatively to suitably positioned recognition sequences. Here, we examine the
      behaviour of a chimeric activator of transcription with two different DNA-binding
      domains, that of the bacteriophage lambda cI protein and that of the Escherichia
      coli cyclic AMP receptor protein. We show that these two DNA-binding moieties,
      when present in the same molecule, can bind co-operatively to a pair of cognate
      recognition sites located upstream of a test promoter, thereby permitting the
      chimera to function as a particularly strong activator of transcription from this
      promoter. Our results show how such a bivalent DNA-binding protein can be used to
      regulate transcription differentially from promoters that bear either one or both
      recognition sites.

PMID- 11532152
TI  - The Neurospora circadian clock regulates a transcription factor that controls
      rhythmic expression of the output eas(ccg-2) gene.
AB  - The circadian clock provides a link between an organism's environment and its
      behaviour, temporally phasing the expression of genes in anticipation of daily
      environmental changes. Input pathways sense environmental information and
      interact with the clock to synchronize it to external cycles, and output pathways
      read out from the clock to impart temporal control on downstream targets. Very
      little is known about the regulation of outputs from the clock. In Neurospora
      crassa, the circadian clock transcriptionally regulates expression of the clock
      controlled genes, including the well-characterized eas(ccg-2) gene. Dissection of
      the eas(ccg-2) gene promoter previously localized a 68 bp sequence containing an
      activating clock element (ACE) that is both necessary and sufficient for rhythmic
      activation of transcription by the circadian clock. Using electrophoretic
      mobility shift assays (EMSAs), we have identified light-regulated nuclear protein
      factors that bind specifically to the ACE in a time-of-day-dependent fashion,
      consistent with their role in circadian regulation of expression of eas(ccg-2).
      Nucleotides in the ACE that interact with the protein factors were determined
      using interference binding assays, and deletion of the core interacting sequences
      affected, but did not completely eliminate, rhythmic accumulation of eas(ccg-2)
      mRNA in vivo, whereas deletion of the entire ACE abolished the rhythm. These data
      indicate that redundant binding sites for the protein factors that promote
      eas(ccg-2) rhythms exist within the 68 bp ACE. The ACE binding complexes formed
      using protein extracts from cells with lesions in central components of the
      Neurospora circadian clock were identical to those formed with extracts from wild
      type cells, indicating that other proteins directly control eas(ccg-2) rhythmic
      expression. These data suggest that the Neurospora crassa circadian clock
      regulates an unknown transcription factor, which in turn activates the expression
      of eas(ccg-2) at specific times of the day.

PMID- 11532153
TI  - The CRP-cAMP complex and downregulation of the glnAp2 promoter provides a novel
      regulatory linkage between carbon metabolism and nitrogen assimilation in
      Escherichia coli.
AB  - In Escherichia coli, glnA (encoding glutamine synthetase) is transcribed from two
      promoters (glnAp1 and glnAp2). The glnAp1 is a sigma(70)-dependent promoter that
      is activated by the cAMP receptor protein (CRP). Under nitrogen-deficient growth
      conditions, glnAp1 is repressed by NtrC-phosphate. The downstream glnAp2 promoter
      is sigma(54)-dependent and is activated by NtrC-phosphate. Here, we show that
      glnAp2 expression is affected by different carbon sources and that the CRP-cAMP
      complex inhibits the glnAp2 promoter activity. Primer extension and KMnO4
      footprinting analysis indicate that the inhibitory effect is at the
      transcriptional level in vivo. When glnAp2 is activated by NifA, a similar
      inhibitory effect by CRP-cAMP is observed. Site-directed mutagenesis and deletion
      analysis indicate that the characterized and putative CRP-binding sites located
      in the upstream region of the glnAp2 promoter are not essential for the
      inhibitory effect. CRP-cAMP inhibits sigma(54)-dependent glnAp2 strongly, by 21
      fold. By activating glnAp1 and downregulating glnAp2, the overall effect of CRP
      cAMP on glnA expression is an approximately fourfold reduction, which correlates
      with the reduction of gamma-glutamyl transferase activities in the cells. We
      propose therefore that a physiological role of CRP-cAMP activation of glnAp1 is
      to partially compensate for CRP-cAMP downregulation of glnAp2, allowing a low but
      non-negligible level of expression of the important genes transcribed from it. A
      novel regulatory linkage between carbon and nitrogen regulons is proposed.

PMID- 11532154
TI  - Horizontal gene transfer and host specificity of beta-haemolytic streptococci:
      the role of a putative composite transposon containing scpB and lmb.
AB  - Beta-haemolytic streptococci are important human and animal pathogens: their
      genetic traits that are associated with the ability to infect human hosts remain,
      however, unclear. The surface protein, Lmb, mediates the adherence of
      Streptococcus agalactiae to human laminin. For further analysis of the
      corresponding gene, the adjacent genomic regions were sequenced. Lmb is localized
      on a putative composite transposon of 16 kb and is flanked by two copies of a
      novel insertion sequence element (ISSag2). It harbours the genes scpB and lmb,
      which are 98% identical with the respective genes of Streptococcus pyogenes.
      Analysis of the distribution of these genes and ISSag2 among 131 streptococcal
      strains revealed that all of the human isolates, but only 20% (12 of 61) of the
      animal isolates, contained scpB and lmb or their homologues. To investigate if
      the putative transposon can be mobilized, an erythromycin resistance marker was
      incorporated into the lmb gene of S. agalactiae. Screening for mutant strains
      with a regained susceptibility for erythromycin identified strains with a
      deletion of scpB, lmb, and one copy of ISSag2. We hypothesize that a horizontal
      gene transfer caused the exchange of scpB and lmb and that the ability of S.
      pyogenes, S. agalactiae and group C and G streptococcal strains to colonize or
      infect human hosts is dependent on their presence.

PMID- 11532155
TI  - Convergence of two global transcriptional regulators on nitrogen induction of the
      stress-acclimation gene nblA in the cyanobacterium Synechococcus sp. PCC 7942.
AB  - Cyanobacteria respond to environmental stress conditions by degrading their
      phycobilisomes, the light harvesting complexes for photosynthesis. The expression
      of nblA, a key gene in this process, is controlled by the response regulator NblR
      in Synechococcus sp. PCC 7942. Here we show that, under nitrogen stress, nblA is
      also regulated by NtcA, the global regulator for nitrogen control. NtcA
      activation of nblA was found to be nitrogen-specific and did not take place under
      sulphur stress. Transcripts from the two major transcription start points (tsp)
      for the nblA gene were induced in response to nitrogen and sulphur starvation.
      The most active one (tspII) required both NblR and NtcA to induce full nblA
      expression under nitrogen starvation. NblR and NtcA bound in vitro to a DNA
      fragment from the nblA promoter region, suggesting that, under nitrogen stress,
      both NblR and NtcA activate the main regulated promoter (PnblA-2) by direct DNA
      binding. The structure of PnblA-2 differs from that of the canonical NtcA
      activated promoter and it is therefore proposed to represent a novel type of NtcA
      dependent promoter. We analysed expression patterns from ntcA and selected NtcA
      targets in NtcA(-), NblR(-) and wild-type strains, and discuss data suggesting
      further interrelations between phycobilisome degradation and nitrogen
      assimilation regulatory pathways.

PMID- 11532156
TI  - Nuclease activity is essential for RecBCD recombination in Escherichia coli.
AB  - RecBCD has two conflicting roles in Escherichia coli. (i) As ExoV, it is a potent
      double-stranded (ds)DNA exonuclease that destroys linear DNA produced by
      restriction of foreign DNA. (ii) As a recombinase, it promotes repair of dsDNA
      breaks and genetic recombination in the vicinity of chi recombination hot-spots.
      These paradoxical roles are accommodated by chi-dependent attenuation of RecBCD
      exonuclease activity and concomitant conversion of the enzyme to a recombinase.
      To challenge the proposal that chi converts RecBCD from a destructive exonuclease
      to a recombinogenic helicase, we mutated the nuclease catalytic centre of RecB
      and tested the resulting mutants for genetic recombination and DNA repair in
      vivo. We predicted that, if nuclease activity inhibits recombination and helicase
      activity is sufficient for recombination, the mutants would be constitutive
      recombinases, as has been seen in recD null mutants. Conversely, if nuclease
      activity is required, the mutants would be recombination deficient. Our results
      indicate that 5' --> 3' exonuclease activity is essential for recombination by
      RecBCD at chi recombination hot-spots and at dsDNA ends in recD mutants. In the
      absence of RecB-dependent nuclease function, recombination becomes entirely
      dependent on the 5' --> 3' single-stranded (ss)DNA exonuclease activity of RecJ
      and the helicase activity of RecBC(D).

PMID- 11532157
TI  - Apoptosis in amyotrophic lateral sclerosis: a review of the evidence.
AB  - Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease
      primarily affecting the upper and lower motor neurones of the central nervous
      system. Recently, a lot of interest has been generated by the possibility that a
      mechanism of programmed cell death, termed apoptosis, is responsible for the
      motor neurone degeneration in this condition. Apoptosis is regulated through a
      variety of different pathways which interact and eventually lead to controlled
      cell death. Apart from genetic regulation, factors involved in the control of
      apoptosis include death receptors, caspases, Bcl-2 family of oncoproteins,
      inhibitor of apoptosis proteins (IAPs), inhibitors of IAPs, the p53 tumour
      suppressor protein and apoptosis-related molecules. The first part of this
      article will give an overview of the current knowledge of apoptosis. In the
      second part of this review, we will examine in detail the evidence for and
      against the contribution of apoptosis in motor neurone cell death in ALS, looking
      at cellular-, animal- and human post-mortem tissue-based models. In a chronic
      neurodegenerative disease such as ALS, conclusive evidence of apoptosis is likely
      to be difficult to detect, given the rapidity of the apoptotic cell death process
      in relation to the relatively slow time course of the disease. Although a
      complete picture of motor neurone death in ALS has not been fully elucidated,
      there is good and compelling evidence that a programmed cell death pathway
      operates in this disorder. The strongest body of evidence supporting this comes
      from the findings that, in ALS, changes in the levels of members of the Bcl-2
      family of oncoproteins results in a predisposition towards apoptosis, there is
      increased expression or activation of caspases-1 and -3, and the dying motor
      neurones in human cases exhibit morphological features reminiscent of apoptosis.
      Further supporting evidence comes from the detection of apoptosis-related
      molecules and anti-Fas receptor antibodies in human cases of ALS. However, the
      role of the p53 protein in cell death in ALS is at present unclear. An
      understanding of the mechanism of programmed cell death in ALS may provide
      important clues for areas of potential therapeutic intervention for
      neuroprotection in this devastating condition.

PMID- 11532158
TI  - Mast cells and multiple sclerosis: a quantitative analysis.
AB  - The average number of mast cells observed in multiple sclerosis (MS) plaques from
      four patients, was 0.35 mast cells per mm2. This number represents 1/100 of the
      amount found in normal human skin. Most mast cells were observed in the border
      zones of the MS plaques and were clustered in restricted areas along venules and
      capillaries, which represent the main area of oedema formation in the brain. This
      cell type may be considered as a contributor to the pathogenesis of oedema
      formation and subsequent myelin destruction in MS.

PMID- 11532159
TI  - Skeletal muscle pathology in autosomal dominant Emery-Dreifuss muscular dystrophy
      with lamin A/C mutations.
AB  - We present our observations on the skeletal muscle pathology of nine cases from
      seven families of autosomal dominant Emery-Dreifuss muscular dystrophy (ADEDMD)
      with identified mutations in the lamin A/C gene, aged 2-35 years at the time of
      biopsy. The severity of pathological change was moderate and the most common
      features were variation in fibre size (hypertrophy and atrophy), an increase in
      internal nuclei and smaller diameter fibres with high oxidative enzyme activity.
      Only one case showed necrosis, which was present in two separate samples taken
      from the quadriceps and tibialis anterior, at different ages. Immunocytochemistry
      detected an age-related reduction of laminin beta1 on the muscle fibres in
      adolescent and adult cases. Antibodies to lamins A and A/C, and emerin did not
      reveal any detectable differences from controls. Electron microscopy of two out
      of three cases showed an abnormal distribution of heterochromatin in many fibre
      nuclei. Our results show that dystrophic changes in skeletal muscle are not a
      major feature of ADEDMD, and that nuclear abnormalities may be detected with
      electron microscopy. Immunodetection of reduced laminin beta1 may be a useful
      secondary marker in adults with this disorder, as immunocytochemistry of lamins
      is not yet of diagnostic use.

PMID- 11532160
TI  - The development of necrosis and apoptosis in glioma: experimental findings using
      spheroid culture systems.
AB  - Cell death in gliomas may occur either by apoptosis, or, in the case of high
      grade tumours, by necrosis, but questions remain as to the pathogenesis and
      relationship between these processes. The development of cell death was
      investigated in multicellular glioma spheroid cultures. Spheroids model the
      development of cell death due to diffusion gradients in a three-dimensional
      system without confounding influences of immune response, pressure gradients,
      etc. Spheroid cultures were established from four malignant glioma cell lines:
      U87, U373, MOG-G-CCM and A172; harvested from culture at weekly intervals and
      stained with Haematoxylin and Eosin (H&E), TdT-mediated dUTP-X nick end labelling
      (TUNEL) and by immunohistochemistry for vimentin, Glial Fibrillary Acidic Protein
      (GFAP) and Ki67. Annexin V flow cytometry and counts of apoptotic cells on H & E
      stained sections were performed to assess levels of apoptosis. Modes of cell
      death were also characterized by electron microscopy. Spatially separate zones of
      proliferation, differentiation and central cell death developed with increasing
      spheroid diameter. Central cell death developed at a predictable radius (300-400
      microm) for each cell line. Ultrastructural examination showed this to be
      necrotic in type. Apoptosis was most reliably assayed by morphological counts
      using H & E. Basal levels of apoptosis were low (< 0.5%), but increased with
      increasing spheroid diameter (> 2% in U87). In particular, levels of apoptosis
      rose following development of central necrosis and apoptoses were most abundant
      in the peri-necrotic zone. There were quantitative differences in the levels of
      apoptosis and necrosis between glioma cell lines. The predictable onset of
      necrosis in the spheroids will allow us to investigate the pathogenesis of
      necrosis and events in prenecrotic cells. There is a relationship between the
      development of necrosis and apoptosis in this model and these processes can be
      separately assayed. Further in vitro and genetic studies will enable us to study
      these events and interactions in greater detail than is possible using other cell
      culture and in vivo systems.

PMID- 11532161
TI  - Replicative Mcm2 protein as a novel proliferation marker in oligodendrogliomas
      and its relationship to Ki67 labelling index, histological grade and prognosis.
AB  - The grading and prognostic assessment of oligodendrogliomas is severely
      constrained and there remains a need for improved diagnosis. Recently, we have
      identified the minichromosome maintenance (MCM) family of proteins as a novel
      class of proliferation markers. Mcm2 is a protein which forms part of the
      prereplicative complex. It is necessary for this complex to be assembled at
      origins of future DNA replication during the G1 phase to allow genome replication
      in the subsequent S phase. Our aim was to determine whether analysis of Mcm2
      protein expression in oligodendrogliomas is of diagnostic value.
      Immunohistochemical staining for Mcm2 was performed on an archival series of 32
      oligodendrogliomas. These tumours have been previously characterized for Ki67,
      mitotic labelling index and outcome. Cells showing expression of Mcm2 were
      quantified as a percentage to provide an Mcm2 labelling index. We have
      demonstrated a good correlation between Mcm2 and Ki67 labelling indices (r =
      0.76, P < 0.01) but immunohistochemistry for Mcm2 consistently identified a
      higher proportion of cells. Mcm2 labelling index was higher in grade III than
      grade II tumours (P < 0.001). Cases with a high Mcm2 labelling index showed a
      poorer prognosis than those with a low index (P = 0.497) in univariate analysis,
      but with wide variation in this small series. Demonstration of Mcm2 expression is
      of value to demonstrate the proliferative fraction of tumours and is likely to be
      of prognostic value. Its study in a larger series is therefore warranted.

PMID- 11532162
TI  - Alpha-synuclein pathology is highly dependent on the case selection.
AB  - Lewy bodies and dystrophic neurites have been considered a common substrate for
      dementia, but they are also frequently found in the normal elderly population.
      The primary component of this pathology involves alpha-synuclein. The main
      objective of the present study was to estimate the prevalence of alpha-synuclein
      pathology in aged population, and to assess its relative significance in relation
      to dementia. The study also investigated whether differences could be detected in
      alpha-synuclein pathology in relation to age, gender or concomitant Alzheimer's
      pathology. Furthermore, the influence of sampling strategies was analysed. Alpha
      synuclein pathology was assessed using immunohistochemistry in well-characterized
      post-mortem material. The investigation included patients from a longitudinal
      study of dementia of Alzheimer's type (n = 103, 85% demented), subjects from a
      prospective longitudinal clinical study of ageing (n = 69, 29% demented), a
      cohort of consecutive clinical post-mortem cases collected for 1 year (n = 262,
      12% demented), a sample of forensic post-mortem cases collected for 6 months (n =
      121, 15% demented) and a sample of Brain Bank material (n = 234, 26% demented).
      Overall, alpha-synuclein pathology was found in 14% of all 774 subjects over 40
      years of age, and this percentage varied from 8% to 27% according to sampling
      strategies. These results indicate that the prevalence of alpha-synuclein
      pathology clearly depends on the selection of material. Furthermore alpha
      synuclein pathology was found in 23% of clinically demented patients and in 11%
      of non-demented subjects. The load of alpha-synuclein pathology was significantly
      greater in the demented patients versus non-demented subjects indicating that
      alpha-synuclein pathology is indeed of importance in the pathogenesis of
      dementia.

PMID- 11532164
TI  - Knock-out of the plastid ribosomal protein L11 in Arabidopsis: effects on mRNA
      translation and photosynthesis.
AB  - The prpl11-1 mutant of Arabidopsis thaliana was identified among a collection of
      T-DNA tagged lines on the basis of a decrease in the effective quantum yield of
      photosystem II. The mutation responsible was localized to Prpl11, a single-copy
      nuclear gene that encodes PRPL11, a component of the large subunit of the plastid
      ribosome. The amino acid sequence of Arabidopsis PRPL11 is very similar to those
      of L11 proteins from spinach and prokaryotes. In the prpl11-1 mutant,
      photosensitivity and chlorophyll fluorescence parameters are significantly
      altered owing to changes in the levels of thylakoid protein complexes and stromal
      proteins. The abundance of most plastome transcripts examined, such as those of
      genes coding for the photosystem II core complex and RbcL, is not decreased.
      Plastid ribosomal RNA accumulates in wild-type amounts, and the assembly of
      plastid polysomes on the transcripts of the rbcL, psbA and psbE genes remains
      mainly unchanged in mutant plants, indicating that lack of PRPL11 affects neither
      the abundance of plastid ribosomes nor their assembly into polysomes. However, in
      vivo translation assays demonstrate that the rate of translation of the large
      subunit of Rubisco (RbcL) is significantly reduced in prpl11-1 plastids. Our data
      suggest a major role for PRPL11 in plastid ribosome activity per se, consistent
      with its location near the GTPase-binding centre of the chloroplast 50S ribosomal
      subunit. Additional effects of the mutation, including the pale green colour of
      the leaves and a drastic reduction in growth rate under greenhouse conditions,
      are compatible with reduced levels of protein synthesis in plastids.

PMID- 11532163
TI  - The National NeuroAIDS Tissue Consortium: a new paradigm in brain banking with an
      emphasis on infectious disease.
AB  - The National NeuroAIDS Tissue Consortium (NNTC) was founded in 1998, in response
      to the scientific need for well-characterized central nervous system (CNS) and
      peripheral nervous system (PNS) tissues and fluids from HIV-infected individuals.
      In addition to performing the routine functions of non-transplant anatomic tissue
      banks, the Consortium offers a unique model for the integration of independent
      research entities in order to provide well-characterized tissues and fluids for
      the international research community. Herein, we describe the structure of the
      Consortium, pointing out the inherent strengths of linking together multiple
      independent sites for the purpose of banking HIV-infected nervous system tissues.
      We describe the neuropathology protocol that was adopted and successfully
      implemented at the four participating banks of the Consortium.

PMID- 11532165
TI  - Evidence for a role in growth and salt resistance of a plasma membrane H+-ATPase
      in the root endodermis.
AB  - The plasma membrane of plant cells is energized by an electrochemical gradient
      produced by P-type H+-ATPases (proton pumps). These pumps are encoded by at least
      12 genes in Arabidopsis. Here we provide evidence that isoform AHA4 contributes
      to solute transport through the root endodermis. AHA4 is expressed most strongly
      in the root endodermis and flowers, as suggested by promoter-GUS reporter assays.
      A disruption of this pump (aha4-1) was identified as a T-DNA insertion in the
      middle of the gene (after VFP(574)). Truncated aha4-1 transcripts accumulate to
      approximately 50% of the level observed for AHA4 mRNA in wild-type plants. Plants
      homozygous for aha4-1 (-/-) show a subtle reduction in root and shoot growth
      compared with wild-type plants when grown under normal conditions. However, a
      mutant phenotype is very clear in plants grown under salt stress (e.g., 75 or 110
      mM NaCl). In leaves of mutant plants subjected to Na stress, the ratio of Na to K
      increased 4-5-fold. Interestingly, the aha4-1 mutation appears to be semidominant
      and was only partially complemented by the introduction of additional wild-type
      copies of AHA4. These results are consistent with the hypothesis that aha4-1 may
      produce a dominant negative protein or RNA that partially disrupts the activity
      of other pumps or functions in the root endodermal tissue, thereby compromising
      the function of this cell layer in controlling ion homeostasis and nutrient
      transport.

PMID- 11532166
TI  - The Arabidopsis aberrant growth and death2 mutant shows resistance to Pseudomonas
      syringae and reveals a role for NPR1 in suppressing hypersensitive cell death.
AB  - A novel Arabidopsis mutant has been identified with constitutive expression of
      GST1-GUS using plants with a pathogen-responsive reporter transgene containing
      the beta-glucuronidase (GUS) coding region driven by the GST1 promoter. The
      recessive mutant, called agd2 (aberrant growth and death2), has salicylic acid
      (SA)-dependent increased resistance to virulent and avirulent strains of the
      bacterial pathogen Pseudomonas syringae, elevated SA levels, a low level of
      spontaneous cell death, callose deposition, and enlarged cells in leaves. The
      enhanced resistance of agd2 to virulent P. syringae requires the SA signaling
      component NONEXPRESSOR OF PR1 (NPR1). However, agd2 renders the resistance
      response to P. syringae carrying avrRpt2 NPR1-independent. Thus agd2 affects both
      an SA- and NPR1-dependent general defense pathway and an SA-dependent, NPR1
      independent pathway that is active during the recognition of avirulent P.
      syringae. agd2 plants also fail to show a hypersensitive cell death response (HR)
      unless NPR1 is removed. This novel function for NPR1 is also apparent in
      otherwise wild-type plants: npr1 mutants show a stronger HR, while NPR1
      overproducing plants show a weaker HR when infected with P. syringae carrying the
      avrRpm1 gene. Spontaneous cell death in agd2 is partially suppressed by npr1,
      indicating that NPR1 can suppress or enhance cell death depending on the cellular
      context. agd2 plants depleted of SA show a dramatic exacerbation of the cell
      growth phenotype and increased callose deposition, suggesting a role for SA in
      regulating growth and this cell-wall modification. AGD2 may function in cell
      death and/or growth control as well as the defense response, similarly to what
      has been described in animals for the functions of NFkappaB.

PMID- 11532167
TI  - 1-Deoxy-D-xylulose 5-phosphate reductoisomerase and plastid isoprenoid
      biosynthesis during tomato fruit ripening.
AB  - The recently discovered 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway for the
      biosynthesis of plastid isoprenoids (including carotenoids) is not fully
      elucidated yet despite its central importance for plant life. It is known,
      however, that the first reaction completely specific to the pathway is the
      conversion of 1-deoxy-D-xylulose 5-phosphate (DXP) into MEP by the enzyme DXP
      reductoisomerase (DXR). We have identified a tomato cDNA encoding a protein with
      homology to DXR and in vivo activity, and show that the levels of the
      corresponding DXR mRNA and encoded protein in fruit tissues are similar before
      and during the massive accumulation of carotenoids characteristic of fruit
      ripening. The results are consistent with a non-limiting role of DXR, and support
      previous work proposing DXP synthase (DXS) as the first regulatory enzyme for
      plastid isoprenoid biosynthesis in tomato fruit. Inhibition of DXR activity by
      fosmidomycin showed that plastid isoprenoid biosynthesis is required for tomato
      fruit carotenogenesis but not for other ripening processes. In addition, dormancy
      was reduced in seeds from fosmidomycin-treated fruit but not in seeds from the
      tomato yellow ripe mutant (defective in phytoene synthase-1, PSY1), suggesting
      that the isoform PSY2 might channel the production of carotenoids for abscisic
      acid biosynthesis. Furthermore, the complete arrest of tomato seedling
      development using fosmidomycin confirms a key role of the MEP pathway in plant
      development.

PMID- 11532168
TI  - Single ribosomal transcription units are linear, compacted Christmas trees in
      plant nucleoli.
AB  - The rDNA transcription units are enormous macromolecular structures located in
      the nucleolus and containing 50-100 RNA polymerases together with the nascent pre
      rRNA attached to the rDNA. It has not previously been possible to visualize
      nucleolar transcription units directly in intact nucleoli, although highly spread
      preparations in the electron microscope have been imaged as "Christmas trees" 2-3
      microm long. Here we determine the relative conformation of individual
      transcription units in Pisum sativum plant nucleoli using a novel labelling
      technique. Nascent transcripts were detected by a highly sensitive silver
      enhanced 1 nm gold procedure, followed by 3D electron microscopy of entire
      nucleoli. Individual transcription units are seen as conical, elongated clusters
      approximately 300 nm in length and 130 nm in width at the thickest end. We
      further show that there were approximately 300 active ribosomal genes in the
      nucleoli examined. The underlying chromatin structure of the transcribing rDNA
      was directly visualized by applying a novel limited extraction procedure to fixed
      specimens in order to wash out the proteins and RNA, thus specifically revealing
      DNA strands after uranyl acetate staining. Using this technique, followed by post
      embedding in situ hybridization, we observed that the nucleolar rDNA fibres are
      not extended but show a coiled, thread-like appearance. Our results show for the
      first time that native rDNA transcription units are linear, compacted Christmas
      trees.

PMID- 11532169
TI  - A fast neutron deletion mutagenesis-based reverse genetics system for plants.
AB  - A new reverse genetics method has been developed to identify and isolate deletion
      mutants for targeted plant genes. Deletion mutant libraries are generated using
      fast neutron bombardment. DNA samples extracted from the deletion libraries are
      used to screen for deletion mutants by polymerase chain reaction (PCR) using
      specific primers flanking the targeted genes. By adjusting PCR conditions to
      preferentially amplify the deletion alleles, deletion mutants were identified in
      pools of DNA samples, each pool containing DNA from 2592 mutant lines. Deletion
      mutants were obtained for 84% of targeted loci from an Arabidopsis population of
      51 840 lines. Using a similar approach, a deletion mutant for a rice gene was
      identified. Thus we demonstrate that it is possible to apply this method to plant
      species other than Arabidopsis. As fast neutron mutagenesis is highly efficient,
      it is practical to develop deletion mutant populations with more complete
      coverage of the genome than obtained with methods based on insertional
      mutagenesis. Because fast neutron mutagenesis is applicable to all plant genetic
      systems, this method has the potential to enable reverse genetics for a wide
      range of plant species.

PMID- 11532170
TI  - Mapping genes on an integrated sorghum genetic and physical map using cDNA
      selection technology.
AB  - Sorghum is an important target of plant genomics. This cereal has unusual
      tolerance to adverse environments, a small genome (750 Mbp) relative to most
      other grasses, a diverse germplasm, and utility for comparative genomics with
      rice, maize and other grasses. In this study, a modified cDNA selection protocol
      was developed to aid the discovery and mapping of genes across an integrated
      genetic and physical map of the sorghum genome. BAC DNA from the sorghum genome
      map was isolated and covalently bound in arrayed tubes for efficient liquid
      handling. Amplifiable cDNA sequence tags were isolated by hybridization to
      individual sorghum BACs, cloned and sequenced. Analysis of a fully sequenced
      sorghum BAC indicated that about 80% of known or predicted genes were detected in
      the sequence tags, including multiple tags from different regions of individual
      genes. Data from cDNA selection using the fully sequenced BAC indicate that the
      occurrence of mislocated cDNA tags is very low. Analysis of 35 BACs (5.25 Mb)
      from sorghum linkage group B revealed (and therefore mapped) two sorghum genes
      and 58 sorghum ESTs. Additionally, 31 cDNA tags that had significant homologies
      to genes from other species were also isolated. The modified cDNA selection
      procedure described here will be useful for genome-wide gene discovery and EST
      mapping in sorghum, and for comparative genomics of sorghum, rice, maize and
      other grasses.

PMID- 11532171
TI  - High-level expression of a synthetic red-shifted GFP coding region incorporated
      into transgenic chloroplasts.
AB  - We describe here a synthetic red-shifted variant of GFP that can be introduced
      into tobacco plastid genomes and is highly expressed in regenerated plants that
      appear normal and fertile. The variant contains the S65G and S72A mutations which
      shift the absorption maximum from the 395 nm of wild-type GFP closer to 488 nm, a
      wavelength emitted by a laser commonly used in confocal microscopy. In addition
      to enhanced fluorescence, the removal of significant absorption below 450 nm will
      potentially facilitate double-labelling experiments. The variant GFP encoded by
      the synthetic gene can be expressed at a high level, forming approximately 5% of
      total leaf protein.

PMID- 11532172
TI  - Chloroplast lysates support directed mutagenesis via modified DNA and chimeric
      RNA/DNA oligonucleotides.
AB  - Chimeric RNA/DNA and modified DNA oligonucleotides have been shown to direct gene
      conversion events in vitro through a process involving proteins from several DNA
      repair pathways. Recent experiments have extended the utility of these molecules
      to plants, and we previously demonstrated that plant cell-free extracts are
      competent to support oligonucleotide-directed genetic repair. Using this system,
      we are studying Arabidopsis DNA-repair mutants and the role of plant proteins in
      the DNA-repair process. Here we describe a method for investigating mechanisms of
      plastid DNA-repair pathways. Using a genetic readout system in bacteria and
      chimeric or modified DNA oligonucleotides designed to direct the conversion of
      mutations in antibiotic resistance genes, we have developed an assay for genetic
      repair of mutations in a spinach chloroplast lysate system. We report genetic
      repair of point and frameshift mutations directed by both types of modified
      oligonucleotides. This system enables the mechanistic study of plastid gene
      repair and facilitates the direct comparison between plant nuclear and organelle
      DNA-repair pathways.

PMID- 11532173
TI  - Elimination of POR expression correlates with red leaf formation in Amaranthus
      tricolor.
AB  - Amaranthus tricolor L. tricolor cv. Earlysplendor, an ornamental amaranth,
      generates red leaves instead of green leaves in late summer to early autumn. Red
      leaf formation was promoted under short-day conditions and delayed by night-break
      treatments. Red leaves were characterized by lower levels of chlorophyll
      accumulation rather than higher levels of red pigment (betacyanin) accumulation.
      However, the metabolic activity toward the production of Mg-protoporphyrin, an
      intermediate in the biosynthesis pathway for chlorophyll, was detected in red
      leaves as well as in green leaves. RNA gel blot analysis was performed to assess
      the expression of nine genes encoding eight enzymes involved in chlorophyll
      biosynthesis. Among these enzymes, red-leaf-specific reduction of gene expression
      was observed only for NADPH-protochlorophyllide oxidoreductase (POR), a key
      enzyme catalyzing a later step of chlorophyll biosynthesis. In addition,
      immunoblot analysis showed no accumulation of POR protein(s) in red leaves. These
      data indicate that the repression of POR gene expression and resultant loss of
      chlorophyll synthesis activity plays a role in red leaf formation of A. tricolor.

PMID- 11532174
TI  - The centromere1 (CEN1) region of Arabidopsis thaliana: architecture and
      functional impact of chromatin.
AB  - We have analysed the centromere 1 (CEN1) of Arabidopsis thaliana by integration
      of genetic, sequence and fluorescence in situ hybridisation (FISH) data. CEN1 is
      considered to include the centromeric core and the flanking left and right
      pericentromeric regions, which are distinct parts by structural and/or functional
      properties. CEN1 pericentromeres are composed of different dispersed repetitive
      elements, sometimes interrupted by functional genes. In contrast the CEN1 core is
      more uniformly structured harbouring only two different repeats. The presented
      analysis reveals aspects concerning distribution and effects of the uniformly
      shaped heterochromatin, which covers all CEN1 regions. A lethal mutation tightly
      linked to CEN1 enabled us to measure recombination frequencies within the
      heterochromatin in detail. In the left pericentromere, the change from eu- to
      heterochromatin is accompanied by a gradual change in sequence composition but by
      an extreme change in recombination frequency (from normal to 53-fold decrease)
      which takes place within a small region spanning 15 kb. Generally,
      heterochromatin is known to suppress recombination. However, the same analysis
      reveals that left and right pericentromere, though similar in sequence
      composition, differ markedly in suppression (53-fold versus 10-fold). The
      centromeric core exhibits at least 200-fold if not complete suppression. We
      discuss whether differences in (fine) composition reflect quantitative and
      qualitative differences in binding sites for heterochromatin proteins and in turn
      render different functional properties. Based on the presented data we estimate
      the sizes of Arabidopsis centromeres. These are typical for regional centromeres
      of higher eukaryotes and range from 4.4 Mb (CEN1) to 3.55 Mb (CEN4).

PMID- 11532175
TI  - Association of the NADPH:protochlorophyllide oxidoreductase (POR) with isolated
      etioplast inner membranes from wheat.
AB  - Membrane association of NADPH:protochlorophyllide oxidoreductase (POR, EC:
      1.6.99.1) with isolated prolamellar bodies (PLBs) and prothylakoids (PTs) from
      wheat etioplasts was investigated. In vitro-expressed radiolabelled POR, with or
      without transit peptide, was used to characterize membrane association
      conditions. Proper association of POR with PLBs and PTs did not require the
      presequence, whereas NADPH and hydrolysable ATP were vital for the process. After
      treating the membranes with thermolysin, sodium hydroxide or carbonate, a firm
      attachment of the POR protein to the membrane was found. Although the PLBs and
      PTs differ significantly in their relative amount of POR in vivo, no major
      differences in POR association capacity could be observed between the two
      membrane systems when exogenous NADPH was added. Experiments run with only an
      endogenous NADPH source almost abolished association of POR with both PLBs and
      PTs. In addition, POR protein carrying a mutation in the putative nucleotide
      binding site (ALA06) was unable to bind to the inner membranes in the presence of
      NADPH, which further demonstrates that the co-factor is essential for proper
      membrane association. POR protein carrying a mutation in the substrate-binding
      site (ALA24) showed less binding to the membranes as compared to the wild type.
      The results presented here introduce studies of a novel area of protein-membrane
      interaction, namely the association of proteins with a paracrystalline membrane
      structure, the PLB.

PMID- 11532176
TI  - Constitutive over-expression of AtGSK1 induces NaCl stress responses in the
      absence of NaCl stress and results in enhanced NaCl tolerance in Arabidopsis.
AB  - GSK3/shaggy-like protein kinases have been shown to play diverse roles in
      development and signal transduction pathways in various organisms. An Arabidopsis
      homologue of GSK3/shaggy-like kinase, AtGSK1, has been shown to be involved in
      NaCl stress responses. In order to further clarify the role of AtGSK1 in NaCl
      stress responses in plants, we generated transgenic Arabidopsis plants that over
      expressed AtGSK1 mRNA. These plants showed enhanced resistance to NaCl stress
      when assayed either as whole plants or by measurement of root growth on NaCl
      plates. In addition, AtGSK1 transgenic plants in the absence of NaCl stress
      showed phenotypic changes, such as accumulation of anthocyanin, that were similar
      to those observed in wild-type plants under NaCl stress. Transgenic plants
      accumulated 30-50% more Na+ than did wild-type plants when subjected to NaCl
      stress, and Ca2+ content was increased by 15-30% in the transgenic plants
      regardless of the NaCl stress level. Northern blotting revealed that AtGSK1 over
      expression induced expression of the NaCl stress-responsive genes AtCP1, RD29A
      and CHS1 in the absence of NaCl stress. In addition, AtCBL1 and AtCP1 were super
      induced in the NaCl-stressed transgenic plants. Taken together, these results
      suggest that AtGSK1 is involved in the signal transduction pathway(s) of NaCl
      stress responses in Arabidopsis.

PMID- 11532177
TI  - Expression of Clarkia S-linalool synthase in transgenic petunia plants results in
      the accumulation of S-linalyl-beta-D-glucopyranoside.
AB  - Petunia hybrida W115 was transformed with a Clarkia breweri S-linalool synthase
      cDNA (lis). Lis was expressed in all tissues analysed, and linalool was detected
      in leaves, sepals, corolla, stem and ovary, but not in nectaries, roots, pollen
      and style. However, the S-linalool produced by the plant in the various tissues
      is not present as free linalool, but was efficiently converted to non-volatile S
      linalyl-beta-D-glucopyranoside by the action of endogenous glucosyltransferase.
      The results presented demonstrate that monoterpene production can be altered by
      genetic modification, and that the compounds produced can be converted by
      endogenous enzymatic activity.

PMID- 11532178
TI  - Regulation of drought tolerance by gene manipulation of 9-cis-epoxycarotenoid
      dioxygenase, a key enzyme in abscisic acid biosynthesis in Arabidopsis.
AB  - Abscisic acid (ABA), a plant hormone, is involved in responses to environmental
      stresses such as drought and high salinity, and is required for stress tolerance.
      ABA is synthesized de novo in response to dehydration. 9-cis-epoxycarotenoid
      dioxygenase (NCED) is thought to be a key enzyme in ABA biosynthesis. Here we
      demonstrate that the expression of an NCED gene of Arabidopsis, AtNCED3, is
      induced by drought stress and controls the level of endogenous ABA under drought
      stressed conditions. Overexpression of AtNCED3 in transgenic Arabidopsis caused
      an increase in endogenous ABA level, and promoted transcription of drought- and
      ABA-inducible genes. Plants overexpressing AtNCED3 showed a reduction in
      transpiration rate from leaves and an improvement in drought tolerance. By
      contrast, antisense suppression and disruption of AtNCED3 gave a drought
      sensitive phenotype. These results indicate that the expression of AtNCED3 plays
      a key role in ABA biosynthesis under drought-stressed conditions in Arabidopsis.
      We improved drought tolerance by gene manipulation of AtNCED3 causing the
      accumulation of endogenous ABA.

PMID- 11532179
TI  - Degradation signals within both terminal domains of the cauliflower mosaic virus
      capsid protein precursor.
AB  - Targeted protein degradation plays an important regulatory role in the cell, but
      only a few protein degradation signals have been characterized in plants. Here we
      describe three instability determinants in the termini of the cauliflower mosaic
      virus (CaMV) capsid protein precursor, of which one is still present in the
      mature capsid protein p44. A modified ubiquitin protein reference technique was
      used to show that these motifs are still active when fused to a heterologous
      reporter gene. The N-terminus of p44 contains a degradation motif characterized
      by proline, glutamate, aspartate, serine and threonine residues (PEST), which can
      be inactivated by mutation of three glutamic acid residues to alanines. The
      signals from the precursor do not correspond to known degradation motifs,
      although they confer high instability on proteins expressed in plant protoplasts.
      All three instability determinants were also active in mammalian cells. The PEST
      signal had a significantly higher degradation activity in HeLa cells, whereas the
      precursor signals were less active. Inhibition studies suggest that only the
      signal within the N-terminus of the precursor is targeting the proteasome in
      plants. This implies that the other two signals may target a novel degradation
      pathway.

PMID- 11532180
TI  - A nuclear gene encoding mitochondrial Delta-pyrroline-5-carboxylate dehydrogenase
      and its potential role in protection from proline toxicity.
AB  - Delta1-pyrroline-5-carboxylate (P5C), an intermediate in biosynthesis and
      degradation of proline (Pro), is assumed to play a role in cell death in plants
      and animals. Toxicity of external Pro and P5C supply to Arabidopsis suggested
      that P5C dehydrogenase (P5CDH; EC 1.2.1.12) plays a crucial role in this process
      by degrading the toxic Pro catabolism intermediate P5C. Also in a Deltaput2 yeast
      mutant, lacking P5CDH, Pro led to growth inhibition and formation of reactive
      oxygen species (ROS). Complementation of the Deltaput2 mutant allowed
      identification of the Arabidopsis P5CDH gene. AtP5CDH is a single-copy gene and
      the encoded protein was localized to the mitochondria. High homology of AtP5CDH
      to LuFIS1, an mRNA up-regulated during susceptible pathogen attack in flax,
      suggested a role for P5CDH in inhibition of hypersensitive reactions. An
      Arabidopsis mutant (cpr5) displaying a constitutive pathogen response was found
      to be hypersensitive to external Pro. In agreement with a role in prevention of
      cell death, AtP5CDH was expressed at a basal level in all tissues analysed. The
      highest expression was found in flowers that are known to contain the highest Pro
      levels under normal conditions. External supply of Pro induced AtP5CDH
      expression, but much more slowly than Pro dehydrogenase (AtProDH) expression.
      Uncoupled induction of the AtProDH and AtP5CDH genes further supports the
      hypothesis that P5C levels have to be tightly controlled. These results indicate
      that, in addition to the well-studied functions of Pro, for example in
      osmoregulation, the Pro metabolism intermediate P5C also serves as a regulator of
      cellular stress responses.

PMID- 11532181
TI  - Silencing of a meristematic gene using geminivirus-derived vectors.
AB  - Geminiviruses are DNA viruses that replicate and transcribe their genes in plant
      nuclei. They are ideal vectors for understanding plant gene function because of
      their ability to cause systemic silencing in new growth and ease of inoculation.
      We previously demonstrated DNA episome-mediated gene silencing from a bipartite
      geminivirus in Nicotiana benthamiana. Using an improved vector, we now show that
      extensive silencing of endogenous genes can be obtained using less than 100 bp of
      homologous sequence. Concomitant symptom development varied depending upon the
      target gene and insert size, with larger inserts producing milder symptoms. In
      situ hybridization of silenced tissue in attenuated infections demonstrated that
      silencing occurs in cells that lack detectable levels of viral DNA. A mutation
      confining the virus to vascular tissue produced extensive silencing in mesophyll
      tissue, further demonstrating that endogenous gene silencing can be separated
      from viral infection. We also show that two essential genes encoding a subunit of
      magnesium chelatase and proliferating cell nuclear antigen (PCNA) can be silenced
      simultaneously from different components of the same viral vector.
      Immunolocalization of silenced tissue showed that the PCNA protein was down
      regulated throughout meristematic tissues. Our results demonstrate that
      geminivirus-derived vectors can be used to study genes involved in meristem
      function in intact plants.

PMID- 11532182
TI  - Biolistic transformation of Arabidopsis root hairs: a novel technique to
      facilitate map-based cloning.
AB  - The final stage of map-based gene isolation is complementation of the mutant
      phenotype with wild-type DNA to determine the exact location of the gene of
      interest. This usually involves Agrobacterium tumefaciens-mediated
      transformation, which is reliable and produces stable transformants. However, the
      process of Agrobacterium transformation may take up to three months to complete.
      If the mutant phenotype can be seen in a single cell, and the wild-type copy of
      the gene can act cell autonomously, then complementation of the whole plant is
      not strictly necessary. We have developed a technique for the biolistic
      transformation of Arabidopsis thaliana root hairs, and used this to test large
      insert clones for complementation of two recessive mutant phenotypes, a procedure
      that takes less than a day. Our results show that biolistic transformation can be
      used with transient assays to conduct rapid tests for complementation by large
      insert clones.

PMID- 11532183
TI  - The ABO blood group system: historical background.

PMID- 11532184
TI  - ABH blood group active glycoconjugates from human red cells.

PMID- 11532185
TI  - Cloning and regulation of the ABO genes.

PMID- 11532186
TI  - Polymorphism and recombination events at the ABO locus: a major challenge for
      genomic ABO blood grouping strategies.
AB  - The blood group ABO gene codes for a glycosyltransferase that adds the ultimate
      monosaccharide to a glycoconjugate and forms the A or B blood group specific
      antigen. The DNA structure of the three major alleles of the human blood group
      ABO system was first described in 1990. This review describes the subsequent
      developments, including the increasing number of variants of these common alleles
      and the underlying mutations thought to be responsible for the occurrence of some
      of the weak subgroups of blood group A and B. Several inactive (O) alleles are
      also now known. Our knowledge of the DNA sequence of the normal A and B alleles
      and of the rare and intriguing cisAB and B(A) phenotypes has resulted in
      plausible explanations for these. Allelic variations outside the translated exons
      have been investigated and resulted in detection of lineage-specific intron
      mutations and the discovery of an enhancer VNTR region affecting the rate of
      transcription at this locus. The occurrence of hybrid alleles can also explain
      hitherto abnormal inheritance in some pedigrees. The detection of hybrid alleles
      has been made possible by the presence of numerous polymorphisms found in the
      various ABO alleles. The role of chi (chi) sequences is discussed. Finally, the
      various genotyping methods available are summarized and their advantages and
      limitations are analysed in the light of the increasing allelic variation.

PMID- 11532187
TI  - Natural and recombinant A and B gene encoded glycosyltransferases.
AB  - The human blood group A and B synthesizing enzymes are glycosyltransferases that
      catalyse the transfer of a monosaccharide residue from UDP-GalNAc and UDP-Gal
      donors, respectively, to alphaFuc1,2-Gal terminated blood group H acceptors.
      Extensive investigations of their substrate specificity and physical properties
      have been carried out since their initial discovery. These studies demonstrated a
      rigid specificity for the acceptor structure, crossover in donor specificity and
      immunological similarity along with chromatographic differences. Cloning of the
      enzymes has shown that they are highly homologous, differing in only four of
      their 354 amino acids. Changing the residues Arg176-->Gly, Gly235-->Ser, Leu266-
      >Met and Gly 268-->Ala converts the enzyme specificity from blood group A to
      blood group B glycosyltransferase. Structure function investigations have been
      carried out by systematic interchange and modification of these four critical
      amino acids. These studies have shown that donor specificity is attributed to the
      last two amino acids. Mutants have also been produced with greatly enhanced
      turnover rates as well as hybrid A/B enzymes that catalyse both reactions
      efficiently.

PMID- 11532188
TI  - ABO-incompatibility in solid organ transplantation.
AB  - The most important transplantation antigen system in solid organ transplantation
      is the ABO histo-blood group system. Crossing the ABO barrier in solid organ
      transplantation is usually not done except for emergency liver transplantations.
      Early experiences of crossing the ABO barrier in renal transplantation were very
      disappointing. In the 1970s, clinical trials were started transplanting kidneys
      of subgroup A2 into blood group O recipients. The tissues of the A2 subgroup
      expresses reduced amount of A antigens compared to subgroup A1 and the recipients
      had no special pretreatment and standard immunosuppression. A number of early
      graft losses were experienced but the trial also resulted in several long time
      surviving grafts. A few centres have adapted the concept of A2 to non A kidney
      transplantations with successful results, when the recipient anti-A titres are
      low or reduced prior to transplantation. In the early 1980s one group
      successfully transplanted A1 and B kidneys from living related donors across the
      ABO-barrier using an immunosuppressive protocol consisting of quadruple drugs and
      splenectomy and this protocol was adapted by a few other groups. In Japan, where
      cadaver donors are available in very limited number, the largest number of ABO
      incompatible transplantations have been performed. Altogether more than 300 ABO
      incompatible kidney transplantations have been performed in more than 40 centres
      since 1989. ABO-incompatible liver transplantations have been performed mainly in
      emergency cases and the results have generally been inferior to ABO-compatible
      grafts. In children below the age of three years, liver transplantations across
      the ABO-barrier have been quite successful especially with living related donors.
      Very few ABO-incompatible heart/heart-lung/lung-transplantations have been
      reported with a few successful cases, but the majority have been failures.
      Recently a series of ABO-incompatible heart transplants performed in small
      children have been reported with a high success rate.

PMID- 11532189
TI  - The relationship between ABO histo-blood group, factor VIII and von Willebrand
      factor.
AB  - ABO histo-blood group is a major determinant of plasma levels of factor VIII
      (FVIII) and von Willebrand factor (vWF). Blood group O individuals have
      significantly (approximately 25%) lower plasma levels of both glycoproteins. This
      association is of clinical significance. Low plasma levels of either FVIII or vWF
      have long been established as causes of excess bleeding. Conversely, there is
      accumulating evidence that elevated FVIII-vWF levels may represent an important
      risk factor for ischaemic heart disease and venous thromboembolic disease. In
      spite of the well-documented association between ABO blood group and FVIII-vWF
      levels, the underlying mechanism remains unknown. However, it has been
      established that the ABO effect is primarily mediated through a direct functional
      effect of the ABO locus on plasma vWF levels. Theoretically, ABO blood group may
      alter the rate of vWF synthesis or secretion within endothelial cells.
      Alternatively, ABO group may affect vWF plasma clearance rates. ABH antigenic
      determinants have been identified on the N-linked oligosaccharide chains of
      circulating vWF and FVIII, according to the blood group of the individual. It
      remains unclear whether these carbohydrate structures are responsible for
      mediating the effect of ABO blood group on plasma vWF levels.

PMID- 11532190
TI  - Impaired wound healing in mice deficient in a matricellular protein SPARC
      (osteonectin, BM-40).
AB  - BACKGROUND: SPARC is a matricellular protein involved in cell-matrix
      interactions. From expression patterns at the wound site and in vitro studies,
      SPARC has been implicated in the control of wound healing. Here we examined the
      function of SPARC in cutaneous wound healing using SPARC-null mice and dermal
      fibroblasts derived from them. RESULTS: In large (25 mm) wounds, SPARC-null mice
      showed a significant delay in healing as compared to wild-type mice (31 days
      versus 24 days). Granulation tissue formation and extracellular matrix protein
      production were delayed in small 6 mm SPARC-null wounds initially but were
      resolved by day 6. In in vitro wound-healing assays, while wild-type primary
      dermal fibroblasts showed essentially complete wound closure at 11 hours, wound
      closure of SPARC-null cells was incomplete even at 31 hours. Addition of purified
      SPARC restored the normal time course of wound closure. Treatment of SPARC-null
      cells with mitomycin C to analyze cell migration without cell proliferation
      showed that wound repair remained incomplete after 31 hours. Cell proliferation
      as measured by 3H-thymidine incorporation and collagen gel contraction by SPARC
      null cells were not compromised. CONCLUSIONS: A significant delay in healing
      large excisional wounds and setback in granulation tissue formation and
      extracellular matrix protein production in small wounds establish that SPARC is
      required for granulation tissue formation during normal repair of skin wounds in
      mice. A defect in wound closure in vitro indicates that SPARC regulates cell
      migration. We conclude that SPARC plays a role in wound repair by promoting
      fibroblast migration and thus granulation tissue formation.

PMID- 11532191
TI  - MP20, the second most abundant lens membrane protein and member of the
      tetraspanin superfamily, joins the list of ligands of galectin-3.
AB  - BACKGROUND: Although MP20 is the second most highly expressed membrane protein in
      the lens its function remains an enigma. Putative functions for MP20 have
      recently been inferred from its assignment to the tetraspanin superfamily of
      integral membrane proteins. Members of this family have been shown to be involved
      in cellular proliferation, differentiation, migration, and adhesion. In this
      study, we show that MP20 associates with galectin-3, a known adhesion modulator.
      RESULTS: MP20 and galectin-3 co-localized in selected areas of the lens fiber
      cell plasma membrane. Individually, these proteins purified with apparent
      molecular masses of 60 kDa and 22 kDa, respectively. A 104 kDa complex was formed
      in vitro upon mixing the purified proteins. A 102 kDa complex of MP20 and
      galectin-3 could also be isolated from detergent-solubilized native fiber cell
      membranes. Binding between MP20 and galectin-3 was disrupted by lactose
      suggesting the lectin site was involved in the interaction. CONCLUSIONS: MP20
      adds to a growing list of ligands of galectin-3 and appears to be the first
      representative of the tetraspanin superfamily identified to possess this
      specificity.

PMID- 11532193
TI  - Somatic frameshift mutations in the Bloom syndrome BLM gene are frequent in
      sporadic gastric carcinomas with microsatellite mutator phenotype.
AB  - BACKGROUND: Genomic instability has been reported at microsatellite tracts in few
      coding sequences. We have shown that the Bloom syndrome BLM gene may be a target
      of microsatelliteinstability (MSI) in a short poly-adenine repeat located in its
      coding region. To further characterize the involvement of BLM in tumorigenesis,
      we have investigated mutations in nine genes containing coding microsatellites in
      microsatellite mutator phenotype (MMP) positive and negative gastric carcinomas
      (GCs). METHODS: We analyzed 50 gastric carcinomas (GCs) for mutations in the BLM
      poly(A) tract aswell as in the coding microsatellites of the TGFbeta1-RII,
      IGFIIR, hMSH3, hMSH6, BAX, WRN, RECQL and CBL genes. RESULTS: BLM mutations were
      found in 27% of MMP+ GCs (4/15 cases) but not in any of the MMP negative GCs
      (0/35 cases). The frequency of mutations in the other eight coding regions
      microsatellite was the following: TGFbeta1-RII (60 %), BAX (27%), hMSH6
      (20%),hMSH3 (13%), CBL (13%), IGFIIR (7%), RECQL (0%) and WRN (0%). Mutations in
      BLM appear to be more frequently associated with frameshifts in BAX and in
      hMSH6and/or hMSH3. Tumors with BLM alterations present a higher frequency of
      unstable mono- and trinucleotide repeats located in coding regions as compared
      with mutator phenotype tumors without BLM frameshifts. CONCLUSIONS: BLM
      frameshifts are frequent alterations in GCs specifically associated with
      MMP+tumors. We suggest that BLM loss of function by MSI may increase the genetic
      instability of a pre-existent unstable genotype in gastric tumors.

PMID- 11532194
TI  - Role of CD28/B7 costimulation and IL-12/IL-10 interaction in the radiation
      induced immune changes.
AB  - BACKGROUND: The present paper aims at studying the role of B7/CD28 interaction
      and related cytokine production in the immunological changes after exposure to
      different doses of ionizing radiation. RESULTS: The stimulatory effect of low
      dose radiation (LDR) on the proliferative response of lymphocytes to Con A was
      found to require the presence of APCs. The addition of APCs obtained from both
      low- and high-dose-irradiated mice to splenic lymphocytes separated from low-dose
      irradiated mice caused stimulation of lymphocyte proliferation. B7-1/2 expression
      on APCs was up-regulated after both low and high doses of radiation. There was up
      regulation of CD28 expression on splenic and thymic lymphocytes after LDR and its
      suppression after high dose radiation (HDR), and cytotoxic T lymphocyte
      associated antigen 4 (CTLA-4) expression showed changes in the opposite
      direction. IL-12 secretion by macrophages was stimulated after both low and high
      doses of radiation, but IL-10 synthesis by splenocytes was suppressed by low dose
      radiation and up-regulated by high dose radiation. CONCLUSION: The status of
      CD28/CTLA-4 expression on T lymphocytes in the presence of up-regulated B7
      expression on APCs determined the outcome of the immune changes in response to
      radiation, i.e., up-regulation of CD28 after LDR resulted in immunoenhancement,
      and up-regulation of CTLA-4 associated with down-regulation of CD28 after HDR led
      to immunosuppression. Both low and high doses of radiation up-regulated B7-1/2
      expression on APCs. After LDR, the stimulated proliferative effect of increased
      IL-12 secretion by APCs, reinforced by the suppressed secretion of IL-10, further
      strengthened the intracellular signaling induced by B7-CD28 interaction.

PMID- 11532195
TI  - Monoclonal antibodies against the iron regulated outer membrane Proteins of
      Acinetobacter baumannii are bactericidal.
AB  - BACKGROUND: Iron is an important nutrient required by all forms of life.In the
      case of human hosts,the free iron availability is 10(-18) M,which is far less
      than what is needed for the survival of the invading bacterial pathogen. To
      survive in such conditions, bacteria express new proteins in their outer membrane
      and also secrete iron chelators called siderophores. RESULTS/ DISCUSSION:
      Acinetobacter baumannii ATCC 19606, a nosocomial pathogen which grows under iron
      restricted conditions, expresses four new outer membrane proteins,with molecular
      weight ranging from 77 kDa to 88 kDa, that are called Iron Regulated Outer
      Membrane Proteins (IROMPs). We studied the functional and immunological
      properties of IROMPs expressed by A.baumanii ATCC 19606. The bands corresponding
      to IROMPs were eluted from SDS-PAGE and were used to immunize BALB/c mice for the
      production of monoclonal antibodies. Hybridomas secreting specific antibodies
      against these IROMPs were selected after screening by ELISA and their reactivity
      was confirmed by Western Blot. The antibodies then generated belonged to IgM
      isotype and showed bactericidical and opsonising activities against A.baumanii in
      vitro. These antibodies also blocked siderophore mediated iron uptake via IROMPs
      in bacteria. CONCLUSION: This proves that iron uptake via IROMPs,which is
      mediated through siderophores,may have an important role in the survival of
      A.baumanii inside the host,and helps establishing the infection.

PMID- 11532192
TI  - Intraocular pressure in genetically distinct mice: an update and strain survey.
AB  - BACKGROUND: Little is known about genetic factors affecting intraocular pressure
      (IOP) in mice and other mammals. The purpose of this study was to determine the
      IOPs of genetically distinct mouse strains, assess the effects of factors such as
      age, sex and time of day on IOP in specific strain backgrounds, and to assess the
      effects of specific candidate gene mutations on IOP. RESULTS: Based on over 30
      studied mouse strains, average IOP ranges from approximately 10 to 20 mmHg.
      Gender does not typically affect IOP and aging results in an IOP decrease in some
      strains. Most tested strains exhibit a diurnal rhythm with IOP being the highest
      during the dark period of the day. Homozygosity for a null allele of the carbonic
      anhydrase II gene (Car2n) does not alter IOP while homozygosity for a mutation in
      the leptin receptor gene (Leprdb) that causes obesity and diabetes results in
      increased IOP. Albino C57BL/6J mice homozygous for a tyrosinase mutation (Tyrc
      2J) have higher IOPs than their pigmented counterparts. CONCLUSIONS: Genetically
      distinct mouse strains housed in the same environment have a broad range of IOPs.
      These IOP differences are likely due to interstrain genetic differences that
      create a powerful resource for studying the regulation of IOP. Age, time of day,
      obesity and diabetes have effects on mouse IOP similar to those in humans and
      other species. Mutations in two of the assessed candidate genes (Lepr and Tyr)
      result in increased IOP. These studies demonstrate that mice are a practical and
      powerful experimental system to study the genetics of IOP regulation and disease
      processes that raise IOP to harmful levels.

PMID- 11532196
TI  - Different effects of antisense RelA p65 and NF-kappaB1 p50 oligonucleotides on
      the nuclear factor-kappaB mediated expression of ICAM-1 in human coronary
      endothelial and smooth muscle cells.
AB  - BACKGROUND: Activation of nuclear factor-kappaB (NF-kappaB) is one of the key
      events in early atherosclerosis and restenosis. We hypothesized that tumor
      necrosis factor-alpha (TNF-alpha) induced and NF-kappaB mediated expression of
      intercellular adhesion molecule-1 (ICAM-1) can be inhibited by antisense RelA p65
      and NF-kappaB1 p50 oligonucleotides (RelA p65 and NF-kappaB1 p50). RESULTS:
      Smooth muscle cells (SMC) from human coronary plaque material (HCPSMC, plaque
      material of 52 patients), SMC from the human coronary media (HCMSMC), human
      endothelial cells (EC) from umbilical veins (HUVEC), and human coronary EC
      (HCAEC) were successfully isolated (HCPSMC, HUVEC), identified and cultured
      (HCPSMC, HCMSMC, HUVEC, HCAEC). 12 hrs prior to TNF-alpha stimulus (20 ng/mL, 6
      hrs) RelA p65 and NF-kappaB1 p50 (1, 2, 4, 10, 20, and 30 microM) and controls
      were added for a period of 18 hrs. In HUVEC and HCAEC there was a dose dependent
      inhibition of ICAM-1 expression after adding of both RelA p65 and NF-kappaB1 p50.
      No inhibitory effect was seen after incubation of HCMSMC with RelA p65 and NF
      kappaB1 p50. A moderate inhibition of ICAM-1 expression was found after
      simultaneous addition of RelA p65 and NF-kappaB1 p50 to HCPSMC, no inhibitory
      effect was detected after individual addition of RelA p65 and NF-kappaB1 p50.
      CONCLUSIONS: The data point out that differences exist in the NF-kappaB mediated
      expression of ICAM-1 between EC and SMC. Experimental antisense strategies
      directed against RelA p65 and NF-kappaB1 p50 in early atherosclerosis and
      restenosis are promising in HCAEC but will be confronted with redundant pathways
      in HCMSMC and HCPSMC.

PMID- 11532197
TI  - HIPK2 overexpression leads to stabilization of p53 protein and increased p53
      transcriptional activity by decreasing Mdm2 protein levels.
AB  - BACKGROUND: HIPK2 (homeodomain-interacting protein kinase 2) has been identified
      as a nuclear serine/threonine kinase. A central function of HIPK2 is repressing
      transcription of homeodomain containing transcription factors. RESULTS AND
      CONCLUSIONS: We show here that HIPK2 activates transcription mediated by tumor
      suppressor p53 responsive promoter elements. Overexpression of HIPK2 leads to an
      increase of p53 protein expression or stability, which becomes enhanced further
      in the presence of the DNA damaging drug doxorubicin. The effects of HIPK2 on p53
      are not observed with kinase deficient HIPK2 mutants. However, HIPK2 is not
      sufficient for phosphorylation of three crucial serine residues of p53,
      suggesting that HIPK2-induced p53 activation does not involve phosphorylation of
      p53. Instead, HIPK2 leads to a downregulation of p53-induced Mdm2 protein and
      this may lead to stabilization of p53. Overexpression of HIPK2 does not lead to a
      change of Mdm2 mRNA expression. The data suggest that HIPK2 plays a critical role
      in p53 mediated cellular responses by removing the p53 inhibitor protein Mdm2 via
      modification of the protein itself or its intracellular movement.

PMID- 11532198
TI  - The effect of GABA receptor ligands in experimental spina bifida occulta.
AB  - BACKGROUND: The pathophysiology behind spina bifida and other neural tube defects
      (NTDs) is unclear. Folic acid is one variable, but other factors remain. Studies
      suggest that substances active at the GABA receptor may produce NTDs. To test
      this hypothesis pregnant rats were exposed to either the GABA a agonist muscimol
      (1, 2 or 4 mg/kg), the GABA a antagonist bicuculline (.5, 1, or 2 mg/kg), the
      GABA b agonist baclofen (15, 30, 60 mg/kg), or the GABA b antagonist
      hydroxysaclofen (1, 3, or 5 mg/kg) during neural tube formation. Normal saline
      was used as a control and valproic acid (600 mg/kg) as a positive control. The
      embryos were analyzed for the presence of a spina bifida like NTD. RESULTS: After
      drug administration the pregnancies were allowed to proceed to the 21st day of
      gestation. Then embryos were removed and skeletons staining and cleared.
      Vertebral arch closure was measured. Results indicate that the GABAa receptor
      agonist muscimol, the GABAa receptor antagonist bicuculline, and the GABAb
      agonist baclofen produced NTDs characterized by widening of the vertebral arch.
      Oppositely the GABAb antagonist hydroxysaclofen produced narrowing of the
      vertebral arches. CONCLUSIONS: The findings indicate that GABA a or b ligands are
      capable of altering neural formation. GABA may play a greater than appreciated
      role in neural tube formation and may be important in NTDs. The narrowing of the
      vertebral arch produced by the GABA b antagonist hydroxysalcofen suggests that
      GABA b receptor may play an undefined role in neural tube closure that differs
      from the GABA a receptor.

PMID- 11532199
TI  - Identifying research priorities on infections in older adults: proceedings of an
      interdisciplinary workshop.
AB  - BACKGROUND: Infections pose a substantial burden to the health of older adults.
      In this report, we describe the proceedings of a workshop to formulate and
      prioritize research questions about infections in older adults using an
      interdisciplinary approach. METHODS: Researchers from four sectors (basic
      science, clinical sciences, health services and epidemiology/determinants of
      health) and representatives from various Canadian local, provincial, and federal
      stakeholder groups were invited to a two-day workshop. Five multi-disciplinary
      groups and stakeholders from each of three healthcare settings (long term, acute
      care and community) discussed research priorities for each of the settings. Five
      to ten research questions were identified for each setting. RESULTS: The research
      questions proposed ranged from risk factors and outcomes for different infections
      to the effect of nutrition on infection and the role of alternative and
      complementary medicine in treating infections. Health service issues included
      barriers to immunization, prolongation of hospital length of stay by infection,
      use of care paths for managing infections, and decision-making in determining the
      site of care for individuals with infections. Clinical questions included risk
      factor assessment for infection, the effectiveness of preventative strategies,
      and technology evaluation. Epidemiologic issues included the challenge of
      achieving a better understanding of respiratory infections in the community and
      determining the prevalence of colonization with multi-resistant bacteria.
      CONCLUSIONS: The questions are of direct relevance to researchers in a wide
      variety of fields. Bringing together a multi-disciplinary group of researchers to
      frame and prioritize research questions about aging is feasible, participants
      valued the opinions of people working in other areas.

PMID- 11532200
TI  - An assessment of the usefulness of a rapid immuno-chromatographic test,
      "Determine trade mark malaria pf" in evaluation of intervention measures in
      forest villages of central India.
AB  - BACKGROUND: Plasmodium falciparum malaria, is a major health problem in forested
      tribal belt of central India. Rapid and accurate methods are needed for the
      diagnosis of P. falciparum. We performed a blinded evaluation of the recently
      introduced Determine trade mark malaria pf test (Abbott, Laboratories, Japan)
      compared with microscopy and splenomegaly in children in epidemic prone areas of
      district Mandla to assess the impact of intervention measures. METHODS: Children
      aged 2-10 yrs with and without fever were examined for spleen enlargement by
      medical specialist by establishing a mobile field clinic. From these children
      thick blood smears were prepared from finger prick and read by a technician.
      Simultaneously, rapid tests were performed by a field lab attendant. The figures
      for specificity, sensitivity and predictive values were calculated using
      microscopy as gold standard. RESULTS: In all 349 children were examined. The
      sensitivity and specificity for Determine rapid diagnostic test were 91 and 80%
      respectively. The positive predictive values (PPV), negative predictive values
      (NPV) and accuracy of the test were respectively 79, 91 and 85%. On the contrary,
      the sensitivity and specificity of spleen in detecting malaria infection were 57
      and 74 % respectively with PPV of 73%, NPV 59 % and an accuracy of 65%.
      CONCLUSIONS: Determine trade mark malaria rapid diagnostic test is easier and
      quicker to perform and has other advantages over microscopy in not requiring
      prior training of personnel or quality control. Thus, highlighting the usefulness
      of a rapid antigen test in assessing prevailing malaria situation in remote
      areas.

PMID- 11532201
TI  - Digitoxin medication and cancer; case control and internal dose-response studies.
AB  - BACKGROUND: Digitoxin induces apoptosis in different human malignant cell lines
      in vitro. In this paper we investigated if patients taking digitoxin for cardiac
      disease have a different cancer incidence compared to the general population.
      METHODS: Computer stored data on digitoxin concentrations in plasma from 9271
      patients with cardiac disease were used to define a user population. Age and sex
      matched controls from the Norwegian Cancer Registry were used to calculate the
      number of expected cancer cases. RESULTS: The population on digitoxin showed a
      higher incidence of cancer compared to the control population. However, an
      additional analysis showed that the population on digitoxin had a general
      increased risk of cancer already, before the start on digitoxin.
      Leukemia/lymphoma were the cancer types which stood out with the highest risk in
      the digitoxin population before starting on digitoxin. This indicates that yet
      unknown risk factors exist for cardiovascular disease and lymphoproliferative
      cancer. An internal dose-response analysis revealed a relationship between high
      plasma concentration of digitoxin and a lower risk for leukemia/lymphoma and for
      cancer of the kidney/urinary tract. CONCLUSION: Morbidity and mortality are high
      in the population on digitoxin, due to high age and cardiac disease. These
      factors disturb efforts to isolate an eventual anticancer effect of digitoxin in
      this setting. Still, the results may indicate an anticancer effect of digitoxin
      for leukemia/lymphoma and kidney/urinary tract cancers. Prospective clinical
      cancer trials have to be done to find out if digitoxin and other cardiac
      glycosides are useful as anticancer agents.

PMID- 11532202
TI  - Localization of heat shock protein 20 in swine carotid artery.
AB  - BACKGROUND: Cyclic nucleotides can relax vascular smooth muscle by mechanisms
      distal to myosin regulatory light chain (MRLC) phosphorylation. This mechanism,
      termed relaxation without MRLC dephosphorylation, may be regulated by ser16
      phosphorylation of heat shock protein 20 (HSP20). RESULTS: Confocal imaging of
      HSP20 in smooth muscle tissues revealed that HSP20 was present throughout the
      cytoplasm, although some focal regions of the cytoplasm were found to contain
      more HSP20 than the remaining cytoplasm. The distribution of HSP20 within the
      cytoplasm was not altered by histamine, forskolin, or nitroglycerin. CONCLUSION:
      Cytoplasmic localization of HSP20 is consistent with a potential function of
      HSP20 as a regulator of smooth muscle contractile force.

PMID- 11532203
TI  - Weight loss maintenance in women two to eleven years after participating in a
      commercial program: a survey.
AB  - BACKGROUND: After 5 years, most reports show that less than 10% of people
      maintain a 5% loss from initial body weight. Weight maintenance after 10 years is
      rarely assessed, especially in commercial programs. The current article reports
      weight maintenance in individuals who had participated 2 to 11 years earlier in a
      popular commercial weight loss program based on Canada's Food Guide called
      Mincavi. METHODS: Randomly picked subjects answered a telephone questionnaire.
      Participants, 291 adult women from various regions of the province of Quebec, had
      followed the program 2 to 11 years earlier for at least a month. Body weight at
      the beginning and at the end of treatment was recorded as well as actual weight,
      age and height. Existing records allowed partial verification of the sample.
      RESULTS: Based on corrected weights, percentage of women who maintained at least
      5% of their initial weight loss are as following; 2 years = 43.6% (n = 55), 3
      years = 33.3% (n = 42), 4 years = 23.8% (n = 42), 5-6 years = 38.2% (n = 55), 7-8
      years = 29.4% (n = 51), and 9-11 years; 19.6% (n = 46). Five to eleven years
      after they had participated in the program 29.1% of all women maintained a weight
      loss of at least 5%, while 14.3% maintained a loss of at least 10%. CONCLUSIONS:
      Even though success rate is not as high as could be wished for, results show that
      participation in the Mincavi program can lead to effective weight maintenance
      long after individuals have left it. These findings suggest more thorough studies
      should be conducted on this weight loss program.

PMID- 11532204
TI  - Teaching clinical informatics to third-year medical students: negative results
      from two controlled trials.
AB  - BACKGROUND: Prior educational interventions to increase seeking evidence by
      medical students have been unsuccessful. METHODS: We report two quasirandomized
      controlled trials to increase seeking of medical evidence by third-year medical
      students. In the first trial (1997-1998), we placed computers in clinical
      locations and taught their use in a 6-hour course. Based on negative results, we
      created SUMSearch, an Internet site that automates searching for medical evidence
      by simultaneous meta-searching of MEDLINE and other sites. In the second trial
      (1999-2000), we taught SUMSearch's use in a 5(1/2)-hour course. Both courses were
      taught during the medicine clerkship. For each trial, we surveyed the entire
      third-year class at 6 months, after half of the students had taken the course
      (intervention group). The students who had not received the intervention were the
      control group. We measured self-report of search frequency and satisfaction with
      search quality and speed. RESULTS: The proportion of all students who reported
      searching at least weekly for medical evidence significantly increased from 19%
      (1997-1998) to 42% (1999-2000). The proportion of all students who were satisfied
      with their search results increased significantly between study years. However,
      in neither study year did the interventions increase searching or satisfaction
      with results. Satisfaction with the speed of searching was 27% in 1999-2000. This
      did not increase between studies years and was not changed by the interventions.
      CONCLUSION: None of our interventions affected searching habits. Even with
      automated searching, students report low satisfaction with search speed. We are
      concerned that students using current strategies for seeking medical evidence
      will be less likely to seek and appraise original studies when they enter medical
      practice and have less time.

PMID- 11532205
TI  - Design by necessity.

PMID- 11532206
TI  - Complex genetic diseases: controversy over the Croesus code.
AB  - The polarization of views on how best to exploit new information from the Human
      Genome Project for medicine reflects our ignorance of the genetic architecture
      underlying common diseases: are susceptibility alleles common or rare, neutral or
      deleterious, few or many? Single-nucleotide polymorphism (SNP) technology is
      almost in place to dissect such diseases and to create a personalized medicine,
      but success is critically dependent on the biology and "Nature to be commanded
      must be obeyed" (Francis Bacon, 1620, Novum Organum).

PMID- 11532207
TI  - Orthologs and paralogs - we need to get it right.

PMID- 11532208
TI  - Lessons to be learned from studying Vibrio cholerae in model systems.

PMID- 11532209
TI  - More biology from the sequence.

PMID- 11532210
TI  - Towards a virtual Arabidopsis plant.

PMID- 11532211
TI  - A clustering method for repeat analysis in DNA sequences.
AB  - BACKGROUND: A computational system for analysis of the repetitive structure of
      genomic sequences is described. The method uses suffix trees to organize and
      search the input sequences; this data structure has been used previously for
      efficient computation of exact and degenerate repeats. RESULTS: The resulting
      software tool collects all repeat classes and outputs summary statistics as well
      as a file containing multiple sequences (multi fasta), that can be used as the
      target of searches. Its use is demonstrated here on several complete microbial
      genomes, the entire Arabidopsis thaliana genome, and a large collection of rice
      bacterial artificial chromosome end sequences. CONCLUSIONS: We propose a new
      clustering method for analysis of the repeat data captured in suffix trees. This
      method has been incorporated into a system that can find repeats in individual
      genome sequences or sets of sequences, and that can organize those repeats into
      classes. It quickly and accurately creates repeat databases from small and large
      genomes. The associated software (RepeatFinder), should prove helpful in the
      analysis of repeat structure for both complete and partial genome sequences.

PMID- 11532212
TI  - The adaptive evolution database (TAED).
AB  - BACKGROUND: The Master Catalog is a collection of evolutionary families,
      including multiple sequence alignments, phylogenetic trees and reconstructed
      ancestral sequences, for all protein-sequence modules encoded by genes in
      GenBank. It can therefore support large-scale genomic surveys, of which we
      present here The Adaptive Evolution Database (TAED). In TAED, potential examples
      of positive adaptation are identified by high values for the normalized ratio of
      nonsynonymous to synonymous nucleotide substitution rates (KA/KS values) on
      branches of an evolutionary tree between nodes representing reconstructed
      ancestral sequences. RESULTS: Evolutionary trees and reconstructed ancestral
      sequences were extracted from the Master Catalog for every subtree containing
      proteins from the Chordata only or the Embryophyta only. Branches with high KA/KS
      values were identified. These represent candidate episodes in the history of the
      protein family when the protein may have undergone positive selection, where the
      mutant form conferred more fitness than the ancestral form. Such episodes are
      frequently associated with change in function. An unexpectedly large number of
      families (between 10% and 20% of those families examined) were found to have at
      least one branch with high KA/KS values above arbitrarily chosen cut-offs (1 and
      0.6). Most of these survived a robustness test and were collected into TAED.
      CONCLUSIONS: TAED is a raw resource for bioinformaticists interested in data
      mining and for experimental evolutionists seeking candidate examples of adaptive
      evolution for further experimental study. It can be expanded to include other
      evolutionary information (for example changes in gene regulation or splicing)
      placed in a phylogenetic perspective.

PMID- 11532213
TI  - Comparison of complete nuclear receptor sets from the human, Caenorhabditis
      elegans and Drosophila genomes.
AB  - BACKGROUND: The availability of complete genome sequences enables all the members
      of a gene family to be identified without limitations imposed by temporal,
      spatial or quantitative aspects of mRNA expression. Using the nearly completed
      human genome sequence, we combined in silico and experimental approaches to
      define the complete human nuclear receptor (NR) set. This information was used to
      carry out a comparative genomic study of the NR superfamily. RESULTS: Our
      analysis of the human genome identified two novel NR sequences. Both these
      contained stop codons within the coding regions, indicating that both are
      pseudogenes. One (HNF4 gamma-related) contained no introns and expressed no
      detectable mRNA, whereas the other (FXR-related) produced mRNA at relatively high
      levels in testis. If translated, the latter is predicted to encode a short, non
      functional protein. Our analysis indicates that there are fewer than 50
      functional human NRs, dramatically fewer than in Caenorhabditis elegans and about
      twice as many as in Drosophila. Using the complete human NR set we made
      comparisons with the NR sets of C. elegans and Drosophila. Searches for the >200
      NRs unique to C. elegans revealed no human homologs. The comparative analysis
      also revealed a Drosophila member of NR subfamily NR3, confirming an ancient
      metazoan origin for this subfamily. CONCLUSIONS: This work provides the basis for
      new insights into the evolution and functional relationships of NR superfamily
      members.

PMID- 11532214
TI  - The emerging periplasm-localized subclass of AroQ chorismate mutases, exemplified
      by those from Salmonella typhimurium and Pseudomonas aeruginosa.
AB  - BACKGROUND: Chorismate mutases of the AroQ homology class are widespread in the
      Bacteria and the Archaea. Many of these exist as domains that are fused with
      other aromatic-pathway catalytic domains. Among the monofunctional AroQ proteins,
      that from Erwinia herbicola was previously shown to have a cleavable signal
      peptide and located in the periplasmic compartment. Whether or not this might be
      unique to E. herbicola was unknown. RESULTS: The gene coding for the AroQ protein
      was cloned from Salmonella typhimurium, and the AroQ protein purified from both
      S. typhimurium and Pseudomonas aeruginosa was shown to have a periplasmic
      location. The periplasmic chorismate mutases (denoted *AroQ) are shown to be a
      distinct subclass of AroQ, being about twice the size of cytoplasmic AroQ
      proteins. The increased size is due to a carboxy-terminal extension of unknown
      function. In addition, a so-far novel aromatic aminotransferase was shown to be
      present in the periplasm of P. aeruginosa. CONCLUSIONS: Our analysis has detected
      a number of additional *aroQ genes. The joint presence of *AroQ, cyclohexadienyl
      dehydratase and aromatic aminotransferase in the periplasmic compartment of P.
      aeruginosa comprises a complete chorismate-to-phenylalanine pathway and accounts
      for the "hidden overflow pathway" to phenylalanine described previously.

PMID- 11532215
TI  - Cluster-Rasch models for microarray gene expression data.
AB  - BACKGROUND: We propose two different formulations of the Rasch statistical models
      to the problem of relating gene expression profiles to the phenotypes. One
      formulation allows us to investigate whether a cluster of genes with similar
      expression profiles is related to the observed phenotypes; this model can also be
      used for future prediction. The other formulation provides an alternative way of
      identifying genes that are over- or underexpressed from their expression levels
      in tissue or cell samples of a given tissue or cell type. RESULTS: We illustrate
      the methods on available datasets of a classification of acute leukemias and of
      60 cancer cell lines. For tumor classification, the results are comparable to
      those previously obtained. For the cancer cell lines dataset, we found four
      clusters of genes that are related to drug response for many of the 90 drugs that
      we considered. In addition, for each type of cell line, we identified genes that
      are over- or underexpressed relative to other genes. CONCLUSIONS: The cluster
      Rasch model provides a probabilistic model for describing gene expression
      patterns across samples and can be used to relate gene expression profiles to
      phenotypes.

PMID- 11532216
TI  - Model-based analysis of oligonucleotide arrays: model validation, design issues
      and standard error application.
AB  - BACKGROUND: A model-based analysis of oligonucleotide expression arrays we
      developed previously uses a probe-sensitivity index to capture the response
      characteristic of a specific probe pair and calculates model-based expression
      indexes (MBEI). MBEI has standard error attached to it as a measure of accuracy.
      Here we investigate the stability of the probe-sensitivity index across different
      tissue types, the reproducibility of results in replicate experiments, and the
      use of MBEI in perfect match (PM)-only arrays. RESULTS: Probe-sensitivity indexes
      are stable across tissue types. The target gene's presence in many arrays of an
      array set allows the probe-sensitivity index to be estimated accurately. We
      extended the model to obtain expression values for PM-only arrays, and found that
      the 20-probe PM-only model is comparable to the 10-probe PM/MM difference model,
      in terms of the expression correlations with the original 20-probe PM/MM
      difference model. MBEI method is able to extend the reliable detection limit of
      expression to a lower mRNA concentration. The standard errors of MBEI can be used
      to construct confidence intervals of fold changes, and the lower confidence bound
      of fold change is a better ranking statistic for filtering genes. We can assign
      reliability indexes for genes in a specific cluster of interest in hierarchical
      clustering by resampling clustering trees. A software dChip implementing many of
      these analysis methods is made available. CONCLUSIONS: The model-based approach
      reduces the variability of low expression estimates, and provides a natural
      method of calculating expression values for PM-only arrays. The standard errors
      attached to expression values can be used to assess the reliability of downstream
      analysis.

PMID- 11532217
TI  - Interorganellar crosstalk: new perspectives on signaling from the chloroplast to
      the nucleus.
AB  - Chlorophyll precursors, photosynthetic electron transport, and sugars have all
      been shown to be involved in signaling from the chloroplast to the nucleus,
      suggesting the presence of multiple signaling pathways of coordination between
      these two cellular compartments.

PMID- 11532218
TI  - Nucleomorph genomes: much ado about practically nothing.
AB  - The DNA sequence of one of the smallest eukaryotic genomes has recently been
      finished - that of the reduced nucleus, or nucleomorph, of an algal endosymbiont
      that resides within a cryptomonad host cell. Its sequence promises insights into
      chloroplast acquisition, the constraints on genome size and the basic workings of
      eukaryotic cells.

PMID- 11532219
TI  - The genome of Mycobacterium leprae: a minimal mycobacterial gene set.
AB  - Comparison of the recently sequenced genome of the leprosy-causing pathogen
      Mycobacterium leprae with other mycobacterial genomes reveals a drastic gene
      reduction and decay in M. leprae affecting many metabolic areas, exemplified by
      the retention of a minimal set of genes required for cell-wall biosynthesis.

PMID- 11532221
TI  - AFM 4.0: a toolbox for DNA microarray analysis.
AB  - We have developed a series of programs, collectively packaged as Array File Maker
      4.0 (AFM), that manipulate and manage DNA microarray data. AFM 4.0 is simple to
      use, applicable to any organism or microarray, and operates within the familiar
      confines of Microsoft Excel. Given a database of expression ratios, AFM 4.0
      generates input files for clustering, helps prepare colored figures and Venn
      diagrams, and can uncover aneuploidy in yeast microarray data. AFM 4.0 should be
      especially useful to laboratories that do not have access to specialized
      commercial or in-house software.

PMID- 11532220
TI  - The Smads.
AB  - SUMMARY: The large transforming growth factor-beta (TGFbeta) superfamily of
      secreted proteins regulate the growth, development and differentiation of cells
      in diverse organisms, including nematode worms, flies, mice and humans. Signals
      are initiated upon binding of TGFbeta superfamily members to cell-surface
      serine/threonine kinase receptors and are then propagated by the intracellular
      mediators known as Smads. Activation of Smads results in their translocation from
      the cytoplasm into the nucleus, where they activate or repress transcription
      together with transcription factors so as to regulate target gene expression.
      Most Smads consist of two conserved domains. Mad homology (MH) domains I and 2,
      which are separated by a non-conserved linker region. These domains lack
      enzymatic activity and, instead, Smads mediate their effects through protein
      protein and protein-DNA interactions. Targeted disruption of Smad genes in mice
      has revealed their importance in embryonic development, and a tumor-suppressor
      role for Smads in human cancers has been described. Smads therefore play an
      essential role in mediating TGFbeta-superfamily signals in development and
      disease.

PMID- 11532235
TI  - [Cytotoxic T lymphocyte activity induced by genetic immunization with NV-HC/NS].
AB  - OBJECTIVE: To investigate the immunoprophylactic and immunotherapeutic effects of
      DNA vaccine (NV-HC/NS(3)) after inoculation of mice by target tumor loading
      technique. METHODS: Before or after inoculation with NV-HC/NS(3) intramuscularly,
      BALB/c mice in the experimental group were planted with target tumor cells (SP2/0
      NS(3)), which were derived from BALB/c mice and stably transfected with the
      recombinant plasmid NV-HC/NS(3). Tumor growth and survival rate of the mice
      immunized with NV-HC/NS(3) were compared with those in the control group.
      RESULTS: Tumor mass grew well in all mice in the control group in a few days,
      while no visible tumor mass growth in 40% mice immunized with NV-HC/NS(3) could
      be seen. The survival rate and life span of mice in the experimental group were
      significantly longer than those in the control group. CONCLUSIONS: Specific
      immune activity could be induced by immunization with NV-HC/NS(3). Such effects
      are immunoprophylactic and immunotherapeutic.

PMID- 11532236
TI  - Home treatment for mental health problems: a systematic review.
AB  - OBJECTIVE: This review investigates the effectiveness of 'home treatment' for
      mental health problems in terms of hospitalisation and cost-effectiveness. For
      the purposes of this review, 'home treatment' is defined as a service that
      enables the patient to be treated outside hospital as far as possible and remain
      in their usual place of residence. METHODS - SYSTEMATIC LITERATURE SEARCH: 'Home
      treatment' excluded studies focused on day, residential and foster care. The
      review was based on Cochrane methodology, but non-randomised studies were
      included if they compared two services; these were only analysed if they provided
      evidence of the groups' baseline clinical comparability. METHODS - REVIEW OF
      ECONOMIC EVALUATIONS: Economic evaluations among the studies found were reviewed
      against established criteria. METHODS - IDENTIFICATION OF SERVICE COMPONENTS: A
      three-round Delphi exercise ascertained the degree of consensus among expert
      psychiatrists concerning the important components of community-based services
      that enable them to treat patients outside hospital. The identified components
      were used to construct the follow-up questionnaire. METHODS - FOLLOW-UP OF
      AUTHORS: As a supplement to the information available in the papers, authors of
      all the studies were followed up for data on service components, sustainability
      of programmes and service utilisation. METHODS - DATA ANALYSIS: The outcome
      measure was mean days in hospital per patient per month over the follow-up
      period. (1) Comparative analysis - compared experimental to control services. It
      analysed all studies with available data, divided into 'inpatient-control' and
      'community-control' studies, and tested for associations between service
      components and difference in hospital days. (2) Experimental services analysis -
      analysed only experimental service data and tested for associations between
      service components and hospital days. RESULTS - SYSTEMATIC LITERATURE SEARCH: A
      total of 91 studies were found, conducted over a 30-year period. The majority
      (87) focused on people with psychotic disorders. RESULTS - REVIEW OF ECONOMIC
      EVALUATIONS: Only 22 studies included economic evaluations. They provided little
      conclusive evidence about cost-effectiveness because of problems with the
      heterogeneity of services, sample size, outcome measures and quality of analysis.
      RESULTS - DELPHI EXERCISE: In all, 16 items were rated as 'essential', falling
      into six categories: home environment; skill-mix; psychiatrist involvement;
      service management; caseload size; and health/social care integration. There was
      consensus that caseloads under 25 and flexible working hours over 7 days were
      important, but little support for caseloads under 15 or for 24-hour services, and
      consensus that home visiting was essential, but not on teams being 'explicitly
      dedicated' to home treatment. RESULTS - RESPONSE TO FOLLOW-UP: A total of 60% of
      authors responded, supplying data on service components and hospital days in most
      cases. Other service utilisation data were far less readily available. RESULTS -
      SERVICE CHARACTERISATION AND CLASSIFICATION: The services were homogeneous in
      terms of 'home treatment function' but fairly heterogeneous in terms of other
      components. There was some evidence for a group of services that were
      multidisciplinary, had psychiatrists as integrated team members, had smaller
      caseloads, visited patients at home regularly and took responsibility for both
      health and social care. This was not a cohesive group, however. RESULTS -
      SUSTAINABILITY OF SERVICES: The sustainability of home treatment services was
      modest: less than half the services whose authors responded were still
      identifiable. Services were more likely to be operational if the study had found
      them to reduce hospitalisation significantly. RESULTS - META-ANALYSIS: Meta
      analysis with heterogeneous studies is problematic. The evidence base for the
      effectiveness of services identifiable as 'home treatment' was not strong. Within
      the 'inpatient-control' study group, the mean reduction in hospitalisation was 5
      days per patient per month (for 1-year studies only). No statistical significance
      could be measured for this result. For 'community-control' studies, the reduction
      in hospitalisation was negligible. Moreover, the heterogeneity of control
      services, the wide range of outcome measures and the limited availability of data
      might have confounded the analysis. Regularly visiting at home and dual
      responsibility for health and social care were associated with reduced
      hospitalisation. Evidence for other components was inconclusive. Few conclusions
      could be drawn from the analysis of service utilisation data. RESULTS - LOCATION:
      Studies were predominately from the USA and UK, more of them being from the USA.
      North American studies found a reduction in hospitalisation of 1 day per patient
      per month more than European studies. North American and European services
      differed on some service components, but this was unlikely to account for this
      finding, particularly as no difference was found in their experimental service
      results. CONCLUSIONS - STATE OF RESEARCH: There is a clear need for further
      studies, particularly in the UK. The benefit of home treatment over admission in
      terms of days in hospital was clear, but over other community-based alternatives
      was inconclusive. CONCLUSIONS - NON-RANDOMISED STUDIES: Difficulties in
      systematically searching for non-randomised studies may have contributed to the
      smaller number of such studies found (35, compared with 56 randomised controlled
      trials). This imbalance was compounded by a relatively poor response rate from
      non-randomised controlled trial authors. Including them in the analysis had
      little effect. CONCLUSIONS - LIMITATIONS OF THIS REVIEW: A broad area was
      reviewed in order to avoid the problem of analysing by service label. While
      reviews of narrower areas may risk implying a homogeneity of the services that is
      unwarranted, the current strategy has the drawback that the studies cover a range
      of heterogeneous services. The poor definition of control services, however, is
      ubiquitous in this field, however reviewed areas are defined. Inclusion of mean
      data for which no standard deviations were available was problematic in that it
      prevented measuring the significance of the main findings. The lack of
      availability of this data, however, is an important finding, demonstrating the
      difficulty in seeking certainty in this area. Only days in hospital and cost
      effectiveness were analysed here. The range and lack of uniformity of measures
      used in this field made meta-analysis of other outcomes impossible. It should be
      noted, however, that the findings pertain to these aspects alone. The Delphi
      exercise reported here was limited in being conducted only with psychiatrists,
      rather than a multidisciplinary panel. Its findings were used as a framework for
      the follow-up and analysis. Their possible bias should be borne in mind when
      considering them as findings in themselves. CONCLUSIONS - IMPLICATIONS FOR
      CLINICIANS: The evidence base for home treatment compared with other community
      based services is not strong, although it does show that home treatment reduces
      days spent in hospital compared with inpatient treatment. There is evidence that
      visiting patients at home regularly and taking responsibility for both health and
      social care each reduce days in hospital. CONCLUSIONS - IMPLICATIONS FOR
      CONSUMERS: Services that visit patients at home regularly and those that take
      responsibility for both health and social care are likely to reduce time spent in
      hospital. Psychiatrists surveyed in this review also considered support for
      carers to be essential. The evidence from this review, however, was that few
      services currently have protocols for meeting carers' needs. CONCLUSIONS -
      RECOMMENDATIONS FOR RESEARCH AND COMMISSIONERS: A centrally coordinated research
      strategy, with attention to study design, is recommended. Studies should include
      economic evaluations that report health and social service utilisation. Service
      components should be collected and reported for both experimental and control
      services. Studies should be designed with adequate power and longer durations of
      follow-up and use comparable outcome measures to facilitate meta-analysis.
      Research protocols should be adhered to throughout the studies. It may be
      advisable that independent researchers conduct studies in future. It is no longer
      recommended that home treatment be tested against inpatient care, or that small,
      localised studies replicate existing, more highly powered studies.

PMID- 11532237
TI  - The role of specialist nurses in multiple sclerosis: a rapid and systematic
      review.
AB  - BACKGROUND: Multiple sclerosis (MS) is a disease of the central nervous system.
      The cause is unknown. There are about 80-160 people with MS per 100,000
      population, with twice as many women affected as men. The management of
      individuals with MS includes treatment of acute relapses and chronic symptoms.
      The care of MS patients is provided by various healthcare professionals, such as
      general practitioners (GPs), neurologists, physiotherapists, occupational
      therapists and nurses. Some MS patients have access to an MS specialist nurse,
      although this provision varies geographically. OBJECTIVES: The aim of this report
      is to assess the effectiveness and relative cost-effectiveness of MS specialist
      nurses in improving care and outcomes for patients with MS. METHODS: A systematic
      review of the literature, involving a range of databases, was performed. Full
      details are described in the main report. RESULTS: Only one study was identified
      that tried to evaluate the benefit of MS specialist nurses. The study concluded
      that MS patients and their carers found the MS specialist nurse to be helpful,
      particularly in improving their knowledge of MS, ability to cope, mood and
      confidence about the future. GPs also reported finding the nurse to be helpful
      with their MS patients, and 40% of the GPs stated they would purchase the
      services of an MS specialist nurse if their practices became fundholding.
      However, there were considerable methodological weaknesses inherent in the study
      design, and it was unclear whether the results of the study could be extrapolated
      to other settings or to other MS patient groups. RESULTS - ONGOING RESEARCH:
      There are two ongoing research studies regarding MS specialist nurses. One of
      these studies involves the provision of MS nurses to several areas, but also has
      two control populations to allow evaluation of the health benefits of the nurses
      to MS patients and their carers. This study will help to fill the evidence gap.
      RESULTS - COSTS: The costs of providing MS specialist nurses consist of their
      yearly salary (usually NHS grade G), as well as additional costs for travelling,
      administration, computer and telephone use, a pension scheme, National Insurance
      and study leave. The MS Society of Great Britain and Northern Ireland allows a
      generous total yearly cost to the employer of 40,000 pounds. CONCLUSIONS: The
      present evidence does not make it possible to comment with any certainty on the
      value of specialist nurses in MS. The best evidence available to the authors is
      specialist opinion from neurologists and nurses, and comments from patients with
      MS; this opinion supports the provision of MS specialist nurses. CONCLUSIONS -
      RECOMMENDATIONS FOR RESEARCH: Further research is needed before it will be
      feasible to make firm recommendations on the value of MS specialist nurses
      relative to other possible uses of funds.

PMID- 11532238
TI  - Systematic reviews of the effectiveness of day care for people with severe mental
      disorders: (1) acute day hospital versus admission; (2) vocational
      rehabilitation; (3) day hospital versus outpatient care.
AB  - ***ACUTE DAY HOSPITAL VERSUS ADMISSION FOR ACUTE PSYCHIATRIC DISORDERS***
      BACKGROUND: Inpatient treatment is an expensive way of caring for people with
      acute psychiatric disorders. It has been proposed that many of those currently
      treated as inpatients could be cared for in acute psychiatric day hospitals.
      OBJECTIVE: The aim of this review was to assess the effectiveness and feasibility
      of day hospital versus inpatient care for people with acute psychiatric
      disorders. METHODS - STUDY SELECTION: Eligible studies were randomised controlled
      trials of day hospital versus inpatient care for people with acute psychiatric
      disorders. Studies were excluded if they were primarily concerned with elderly
      people, children, or patients with a diagnosis of organic brain disease or
      substance abuse. METHODS - DATA SOURCES: We searched the Cochrane Controlled
      Trials Register, MEDLINE, EMBASE, CINAHL, PsycLIT, and the reference lists of
      articles. Researchers were approached to identify unpublished studies. Trialists
      were asked to provide individual patient data. METHODS - DATA EXTRACTION: Data
      were extracted independently by two reviewers and cross-checked. METHODS - DATA
      SYNTHESIS: Relative risk (RR) and 95% confidence intervals (CIs) were calculated
      for dichotomous data. Weighted or standardised means were calculated for
      continuous data. Day hospital trials tend to present similar outcomes in slightly
      different formats, making it difficult to synthesise the data. Individual patient
      data were therefore sought so that outcomes could be re-analysed using a common
      format. RESULTS: Nine trials met the inclusion criteria (involving 1568
      randomised patients and 2268 assessed for suitability of day hospital treatment).
      Individual patient data were obtained for four trials (involving 594 people). A
      sensitivity analysis of combined data suggested that day hospital treatment was
      feasible for at worst 23.2% (n = 2268; 95% CI, 21.2 to 25.2) and at best 37.5% (n
      = 1768; 95% CI, 35.2 to 39.8) of those currently admitted to inpatient care.
      Individual patient data from three trials showed no difference in the number of
      days in hospital (combining day hospital days and inpatient days) between day
      hospital patients and controls (n = 465; weighted mean difference (WMD) = -0.38
      days/ month; 95% CI, -1.32 to 0.55). However, compared with controls, patients
      randomised to day hospital care spent significantly more days in day hospital
      care (n = 265; WMD = 2.34 days/month; 95% CI, 1.97 to 2.70) and significantly
      fewer days in inpatient care (n = 265; WMD = -2.75 days/month; 95% CI, -3.63 to 
      1.87). There was no difference between readmission rates for day hospital and
      control patients (n = 667; RR = 0.91; 95% CI, 0.72 to 1.15). Individual patient
      data from three trials showed a significant time-treatment interaction,
      indicating a more rapid improvement in mental state (n = 407; c2 = 9.66; p =
      0.002), but not social functioning (n = 295; c2 = 0.006; p = 0.941) amongst day
      hospital patients. Four of five trials demonstrated that day hospital care was
      cheaper than inpatient care (with overall cost reductions ranging from 20.9% to
      36.9%). CONCLUSIONS: Acute day hospitals are an attractive option in situations
      where demand for inpatient care is high and facilities exist that are suitable
      for conversion. They are a less attractive option when demand for inpatient care
      is low and where effective alternatives already exist. The interpretation of day
      hospital research would be enhanced if future trials made use of the common set
      of outcome measures used in this review. It is important to examine how acute day
      hospital care can be most effectively integrated into a modern community-based
      psychiatric service. ***VOCATIONAL REHABILITATION FOR PEOPLE WITH SEVERE MENTAL
      DISORDERS*** BACKGROUND: People who are disabled by severe mental disorders
      experience high rates of unemployment, but most want to work. Prevocational
      training (PVT) is the traditional approach to helping such people to return to
      work. PVT assumes that a period of preparation is required before those with a
      severe mental disorder can enter into competitive employment. Supported
      Employment (SEm) is a new approach that places clients in competitive employment
      without extended preparation. Both PVT and SEm are widely practised, but it is
      unclear which is the most effective. OBJECTIVES: The overall objective of this
      review was to assess the effectiveness of PVT and SEm relative to each other and
      to standard care (in hospital or the community) for people with severe mental
      disorders. In addition, the review examined the effectiveness of: (1) special
      types of PVT ("clubhouse" model) and SEm (individual placement and support
      model); and (2) modifications for enhancing PVT (e.g. payment or psychological
      interventions). METHODS - STUDY SELECTION: Eligible studies were randomised
      controlled trials (RCTs) examining the effectiveness of vocational rehabilitation
      approaches (PVT and SEm or modifications) for people of working age and suffering
      from a severe mental disorder. METHODS - DATA SOURCES: Relevant trials were
      identified from searches of the Cochrane Schizophrenia Group's specialised
      register, MEDLINE, EMBASE, CINAHL and PsycLIT, and the reference lists of all
      identified studies and review articles. Researchers who were active in the field
      were approached in order to identify unpublished studies. METHODS - DATA
      EXTRACTION: All data were extracted independently by two reviewers and cross
      checked. Continuous data were excluded if they were collected by using an
      unpublished scale or were based on a subset of items from a scale. METHODS - DATA
      SYNTHESIS: For all comparisons, the primary outcome was the number of clients who
      were in competitive employment at various time points. Secondary outcomes were:
      other employment outcomes, clinical outcome and costs. The relative risk (RR) and
      number-needed-to-treat (NNT) were calculated for the relevant categorical
      outcomes. Continuous data were either presented as in the original trial reports
      or, where possible, combined across trials as a standardised mean difference
      score. RESULTS: Eighteen RCTs of reasonable quality were identified: PVT versus
      hospital controls, three RCTs, n = 172; PVT versus community controls, five RCTs,
      n = 1204; modified PVT, four RCTs, n = 423; SEm versus community controls, one
      RCT, n = 256; and SEm versus PVT, five RCTs, n = 491). The main finding was that,
      on the primary outcome (number in competitive employment), SEm was significantly
      more effective than PVT at all time points (e.g. at 12 months, SEm 34% employed,
      PVT 12% employed; RR of not being in competitive employment = 0.76, 95%
      confidence interval 0.69 to 0.84, NNT = 4.5). Clients in SEm also earned more and
      worked more hours per month than those in PVT. CONCLUSIONS: The main finding was
      that SEm was more effective than PVT for patients suffering from a severe mental
      disorder who wanted to work. There was no evidence that PVT was more effective
      than standard community care or hospital care. The implication of these findings
      is that people suffering from mental disorders who want to work should be offered
      the option of SEm. Commissioning agencies would be justified in encouraging
      vocational rehabilitation (VR) providers to develop more SEm schemes. From a
      research perspective, the cost-effectiveness of SEm should be examined in larger
      multicentre trials, both within and outside the USA. There is a case for
      countries outside the USA to survey their existing VR services to determine the
      extent to which the most effective interventions are being offered. ***DAY
      HOSPITAL VERSUS OUTPATIENT CARE FOR PATIENTS WITH PSYCHIATRIC DISORDERS***
      BACKGROUND: This review considers the use of day hospitals as an alternative to
      outpatient care. Two typesof day hospital provision are covered: "day treatment
      programmes" and "day care centres". Day treatment programmes are day hospitals
      that are used to enhance the treatment of patients with anxiety or depressive
      disorders who have failed to respond to outpatient care. Day care centres are day
      hospitals that offer structured support to patients with long-term severe mental
      disorders who would otherwise be treated in an outpatient clinic. OBJECTIVES:
      There were two objectives: first, to assess the effectiveness of day treatment
      programmes versus outpatient care for people with non-psychotic disorders; and,
      secondly, to assess the effectiveness of day care centres versus outpatient care
      for people with severe long-term disorders. METHODS - STUDY SELECTION: Eligible
      studies were randomised controlled trials comparing day hospital care (either a
      day treatment programme or a day care centre) with outpatient care. Studies were
      ineligible if they were largely restricted to patients who were aged under 18 or
      over 65 years or who had a primary diagnosis of substance abuse or organic brain
      disorder. METHODS - DATA SOURCES: Relevant trials were identified from searches
      of the Cochrane Controlled Trials Register, MEDLINE, EMBASE, CINAHL, PsycLIT, and
      the reference lists of all identified studies and review articles. Researchers
      were approached to identify unpublished studies. Trialists were asked to provide
      individual patient data. METHODS - DATA EXTRACTION: All data were extracted
      independently by two reviewers and cross-checked. METHODS - DATA SYNTHESIS:
      Relative risks and 95% confidence intervals were calculated for dichotomous data.
      Standardised mean differences were calculated for continuous data. RESULTS: There
      was evidence from two of the five trials identified suggesting that day treatment
      programmes were superior to continuing outpatient care in terms of improving
      psychiatric symptoms. There was no evidence to suggest that day treatment
      programmes were better or worse than outpatient care on any other clinical or
      social outcome variable or on costs. (ABSTRACT TRUNCATED)

PMID- 11532239
TI  - The measurement and monitoring of surgical adverse events.
AB  - BACKGROUND: Surgical adverse events contribute significantly to postoperative
      morbidity, yet the measurement and monitoring of events is often imprecise and of
      uncertain validity. Given the trend of decreasing length of hospital stay and the
      increase in use of innovative surgical techniques--particularly minimally
      invasive and endoscopic procedures--accurate measurement and monitoring of
      adverse events is crucial. OBJECTIVES: The aim of this methodological review was
      to identify a selection of common and potentially avoidable surgical adverse
      events and to assess whether they could be reliably and validly measured, to
      review methods for monitoring their occurrence and to identify examples of
      effective monitoring systems for selected events. This review is a comprehensive
      attempt to examine the quality of the definition, measurement, reporting and
      monitoring of selected events that are known to cause significant postoperative
      morbidity and mortality. METHODS - SELECTION OF SURGICAL ADVERSE EVENTS: Four
      adverse events were selected on the basis of their frequency of occurrence and
      likelihood of evidence of measurement and monitoring: (1) surgical wound
      infection; (2) anastomotic leak; (3) deep vein thrombosis (DVT); (4) surgical
      mortality. Surgical wound infection and DVT are common events that cause
      significant postoperative morbidity. Anastomotic leak is a less common event, but
      risk of fatality is associated with delay in recognition, detection and
      investigation. Surgical mortality was selected because of the effort known to
      have been invested in developing systems for monitoring surgical death, both in
      the UK and internationally. Systems for monitoring surgical wound infection were
      also included in the review. METHODS - LITERATURE SEARCH: Thirty separate,
      systematic literature searches of core health and biomedical bibliographic
      databases (MEDLINE, EMBASE, CINAHL, HealthSTAR and the Cochrane Library) were
      conducted. The reference lists of retrieved articles were reviewed to locate
      additional articles. A matrix was developed whereby different literature and
      study designs were reviewed for each of the surgical adverse events. Each article
      eligible for inclusion was independently reviewed by two assessors. METHODS -
      CRITICAL APPRAISAL: Studies were appraised according to predetermined assessment
      criteria. Definitions and grading scales were assessed for: content, criterion
      and construct validity; repeatability; reproducibility; and practicality
      (surgical wound infection and anastomotic leak). Monitoring systems for surgical
      wound infection and surgical mortality were assessed on the following criteria:
      (1) coverage of the system; (2) whether or not denominator data were collected;
      (3) whether standard and agreed definitions were used; (4) inclusion of risk
      adjustment; (5) issues related to data collection; (6) postdischarge
      surveillance; (7) output in terms of feedback and wider dissemination. RESULTS -
      SURGICAL WOUND INFECTION: A total of 41 different definitions and 13 grading
      scales of surgical wound infection were identified from 82 studies. Definitions
      of surgical wound infection varied from presence of pus to complex definitions
      such as those proposed by the Centres for Disease Control in the USA. A small
      body of literature has been published on the content, criterion and construct
      validity of different definitions, and comparisons have been made against wound
      assessment scales and multidimensional indices. There are examples of
      comprehensive hospital-based monitoring systems of surgical wound infection,
      mainly under the auspices of nosocomial surveillance. To date, however, there is
      little evidence of systematic measurement and monitoring of surgical wound
      infection after hospital discharge. RESULTS - ANASTOMOTIC LEAK: Over 40
      definitions of anastomotic leak were extracted from 107 studies of upper
      gastrointestinal, hepatopancreaticobiliary and lower gastrointestinal surgery. No
      formal evaluations were found that assessed the validity or reliability of
      definitions or severity scales of anastomotic leak. One definition was proposed
      during a national consensus workshop, but no evidence of its use was found in the
      surgical literature. The lack of a single definition or gold standard hampers
      comparison of postoperative anastomotic leak rates between studies and
      institutions. RESULTS - DEEP VEIN THROMBOSIS: Although a critical review of the
      DVT literature could not be completed within the realms of this review, it was
      evident that a number of new techniques for the detection and diagnosis of DVT
      have emerged in the last 20 years. The group recommends a separate review be
      undertaken of the different diagnostic tests to detect DVT. RESULTS - SURGICAL
      MORTALITY MONITORING SYSTEMS: The definition of surgical mortality is relatively
      consistent between monitoring systems, but duration of follow-up of death
      postdischarge varies considerably. The majority of systems report in-hospital
      mortality rates; only some have the potential to link deaths to national death
      registers. Risk assessment is an important factor and there should be a
      distinction between recording pre-intervention factors and postoperative
      complications. A variety of risk scoring systems was identified in the review.
      Factors associated with accurate and complete data collection include the
      employment of local, dedicated personnel, simple and structured prompts to ensure
      that clinical input is complete, and accurate and automated data capture and
      transfer. CONCLUSIONS: The use of standardised, valid and reliable definitions is
      fundamental to the accurate measurement and monitoring of surgical adverse
      events. This review found inconsistency in the quality of reporting of
      postoperative adverse events, limiting accurate comparison of rates over time and
      between institutions. The duration of follow-up for individual events will vary
      according to their natural history and epidemiology. Although risk-adjusted
      aggregated rates can act as screening or warning systems for adverse events,
      attribution of whether events are avoidable or preventable will invariably
      require further investigation at the level of the individual, unit or department.
      CONCLUSIONS - RECOMMENDATIONS FOR RESEARCH: (1) A single, standard definition of
      surgical wound infection is needed so that comparisons over time and between
      departments and institutions are valid, accurate and useful. Surgeons and other
      healthcare professionals should consider adopting the 1992 Centers for Disease
      Control (CDC) definition for superficial incisional, deep incisional and
      organ/space surgical site infection for hospital monitoring programmes and
      surgical audits. There is a need for further methodological research into the
      performance of the CDC definition in the UK setting. (2) There is a need to
      formally assess the reliability of self-diagnosis of surgical wound infection by
      patients. (3) There is a need to assess formally the reliability of case
      ascertainment by infection control staff. (4) Work is needed to create and agree
      a standard, valid and reliable definition of anastomotic leak which is acceptable
      to surgeons. (5) A systematic review is needed of the different diagnostic tests
      for the diagnosis of DVT. (6) The following variables should be considered in any
      future DVT review: anatomical region (lower limb, upper limb, pelvis); patient
      presentation (symptomatic, asymptomatic); outcome of diagnostic test
      (successfully completed, inconclusive, technically inadequate, negative); length
      of follow-up; cost of test; whether or not serial screening was conducted; and
      recording of laboratory cut-off values for fibrinogen equivalent units. (7) A
      critical review is needed of the surgical risk scoring used in monitoring
      systems. (8) In the absence of automated linkage there is a need to explore the
      benefits and costs of monitoring in primary care. (9) The growing potential for
      automated linkage of data from different sources (including primary care, the
      private sector and death registers) needs to be explored as a means of improving
      the ascertainment of surgical complications, including death. This linkage needs
      to be within the terms of data protection, privacy and human rights legislation.
      (10) A review is needed of the extent of the use and efficiency of routine
      hospital data versus special collections or voluntary reporting.

PMID- 11532240
TI  - The cost-effectiveness of magnetic resonance imaging for investigation of the
      knee joint.
AB  - OBJECTIVES: This study considered the role of magnetic resonance imaging (MRI) in
      the diagnosis of knee injuries in a district general hospital (DGH) setting. The
      principal objective was to identify whether the use of MRI had a major impact on
      the clinical management of patients presenting with chronic knee problems, in
      whom surgery was being considered, whether it reduced overall costs and whether
      it improved patient outcome. In addition, the research: (1) explored the
      'diagnostic accuracy' of initial clinical investigation of the knee by an
      orthopaedic trainee, consultant knee specialist and consultant radiologist; (2)
      considered the variability and diagnostic accuracy of interpretations of knee MRI
      investigations between radiologists; (3) measured the strength of preference for
      the potential diagnostic/therapeutic impact of knee MRI (i.e. the avoidance of
      surgery). METHODS - RANDOMISED CONTROLLED TRIAL: The research was based on a
      single-centre randomised controlled trial conducted at Kent and Canterbury
      Hospital. Patients attending with knee problems in whom surgery was being
      considered were recruited from routine orthopaedic clinics. Most patients had
      been referred by their general practitioner. Patients were randomised to either
      investigation using an MRI scan (MRI trial arm) or investigation using
      arthroscopy (no-MRI trial arm). The study investigated the benefits of knee MRI
      at two levels: diagnostic/therapeutic impact (i.e. avoidance of surgery) and
      patient outcome (using the Short Form with 36 items and EQ-5D quality-of-life
      measurement instruments). Quality of life was assessed at baseline and at 6 and
      12 months. Costs were assessed from the perspectives of the NHS and patients. All
      analyses were by intention to treat. METHODS - SUBSTUDIES (INVESTIGATION OF
      DIAGNOSTIC ACCURACY): For the investigation of diagnostic accuracy of initial
      clinical investigation, the sample comprised 114 patients recruited in a separate
      study conducted at St Thomas' Hospital. The sample was drawn from patients
      presenting at the Accident and Emergency Department with an acute knee injury.
      All study patients received an MRI scan, but initial diagnosis was made without
      access to the scan or the radiologist's report. After 12 months, all clinical
      notes and MRI scans of study patients were reviewed and a final 'reference
      standard' diagnosis for each patient was reached. Comparison was made between the
      diagnosis recorded by each clinician (i.e. orthopaedic trainee, knee specialist
      and consultant radiologist) and the reference diagnosis. METHODS - SUBSTUDIES
      (INVESTIGATION OF THE GENERALISABILITY OF RESULTS): For this substudy, the MRI
      images from 80 patients (recruited at St Thomas' Hospital) were interpreted
      independently by seven consultant radiologists at DGHs and the St Thomas'
      Hospital MRI radiologist. For each area of the knee, the level of agreement
      (measured using weighted kappa) between the responses of the eight radiologists
      and the reference standard diagnosis was assessed. METHODS - SUBSTUDIES
      (INVESTIGATION OF PREFERENCES): The investigation of potential patient
      preferences for the diagnostic/therapeutic impact of MRI was explored using a
      discrete choice conjoint measurement research design. Choices involved selecting
      between two alternative scenarios described using four attributes, and data were
      collected from 585 undergraduate sports science students and analysed using a
      random-effects probit model. RESULTS - RANDOMISED CONTROLLED TRIAL: The trial
      recruited 118 patients (59 randomly allocated to each arm). The two groups were
      similar in important respects at baseline. The central finding was of no
      statistically significant differences between groups in all measures of health
      outcome, although a trend in favour of the no-MRI group was observed. However,
      the use of MRI was found to be associated with a positive diagnostic/therapeutic
      impact: a significantly smaller proportion of patients in the MRI group underwent
      surgery (MRI = 0.41, no-MRI = 0.71; p = 0.001). There was a similar mean overall
      NHS cost for both groups. RESULTS - SUBSTUDIES (INVESTIGATION OF DIAGNOSTIC
      ACCURACY): The exploration of diagnostic accuracy found that, when compared to
      orthopaedic trainees (44% correct diagnoses) or to radiologists reporting an MRI
      scan (68% correct diagnoses), the accuracy rate was higher for knee specialists
      (72% correct diagnoses). RESULTS - SUBSTUDIES (INVESTIGATION OF THE
      GENERALISABILITY OF RESULTS): This generalisability study indicated that, in
      general terms, radiologists in DGHs provide accurate interpretations of knee MRI
      images that are similar to a radiologist at a specialist centre. The one area of
      the knee for which this did not hold was the lateral collateral ligament. RESULTS
      - SUBSTUDIES (INVESTIGATION OF PREFERENCES): The central finding for this
      substudy was that, on average and within the range specified, choices in this
      group of potential patients were not significantly influenced by variation in the
      chance of avoiding surgery. CONCLUSIONS - IMPLICATIONS FOR HEALTHCARE: The
      evidence presented in this report supports the conclusions that the use of MRI in
      patients presenting at DGHs with chronic knee problems in whom arthroscopy was
      being considered did not increase NHS costs overall, was not associated with
      significantly worse outcomes and avoided surgery in a significant proportion of
      patients. CONCLUSIONS - RECOMMENDATIONS FOR FURTHER RESEARCH (IN PRIORITY ORDER):
      (1) The trial data demonstrated that the use of MRI in patients with chronic knee
      problems reduced the need for surgery. However, the link between diagnostic
      processes and changes in health outcome is indirect and the finding of no-MRI
      related effect on health outcome may, therefore, be a consequence of the limited
      power of the trial. Further research to confirm (or contradict) these findings
      would be valuable. (2) The investigation of diagnostic accuracy involved
      comparison with a reference diagnosis established by a panel of two clinical
      members of the research team. It would be interesting to explore the extent to
      which the results would differ using an external panel. (3) The result from the
      preference study, indicating that the potential diagnostic/therapeutic impact of
      knee MRI was not highly valued, is a surprising finding that would be important
      to explore in general public or patient populations. (4) The focus for the trial
      based aspects of this research was the DGH and patients presenting with chronic
      knee problems who were being considered for surgery. Care should be taken in
      generalising from these results to other patient groups (e.g. acute knee
      injuries) or to other settings (e.g. specialist centres). Further clinical trials
      would be required in order to answer such questions.

PMID- 11532241
TI  - Characterization of a delayed rectifier potassium channel in the slowly adapting
      stretch receptor neuron of crayfish.
AB  - Single channel recordings were performed on enzyme-cleaned slowly adapting
      sensory neurons of crayfish, in cell-attached configuration, with a physiological
      K(+) gradient across the neuronal membrane. An outward rectifying, voltage-gated
      K(+) channel with a slope conductance of 13 pS and a K(+) ion permeability of
      P(K)=6.5 x 10(-14) cm(3)/s was characterized. This 13 pS K(+) channel started to
      be activated at around 20 mV depolarization. Its open probability increased upon
      depolarization with V(0.5)= -25.3 mV and P(max)=0.83. The averaged currents
      showed a delay following the onset of depolarization. The activation time
      constant was voltage-dependent. The maximal value was 17.0 ms at -25 mV and at
      +35 mV the time constant was 1.7 ms. Little inactivation was observed throughout
      the 80- or 1500-ms long depolarization pulses. A sum of two exponentials provided
      the optimal fit for open time and closed time distribution. At 80-mV
      depolarization, the open time constants were 0.4 and 10.4 ms; the close time
      constants were 0.4 and 2.3 ms. The first-latency distribution suggested that at
      least two closed states preceded two open states. This 13 pS delayed rectifier
      plays a minor role in the maintenance of the resting membrane potential but
      contributes to the action potential repolarization. It may also modify the
      stretch-induced receptor potential and affect the adaptation behaviours in this
      neuron.

PMID- 11532242
TI  - Excitatory stimulation of neurons in the arcuate nucleus inhibits gastric acid
      secretion via vagal pathways in anesthetized rats.
AB  - It is well established that autonomic control of gastrointestinal function is
      modulated by central autonomic neurotransmission. In this context it has been
      shown that gastrointestinal motility and secretion can be modulated by exogenous
      neuropeptides microinjected into the paraventricular nucleus of the hypothalamus
      (PVN). Furthermore, there is considerable evidence suggesting that neurons
      projecting from the arcuate nucleus (Arc) to the PVN may be the source of
      endogenous neuropeptide release in the PVN. This poses the question whether
      stimulation of neurons in the arcuate nucleus, e.g. by an excitatory amino acid,
      alters gastrointestinal function. In the present study, we investigated the
      effect of an excitatory amino acid, kainate, microinjected into the arcuate
      nucleus on gastric acid secretion in urethane-anesthetized rats. Kainate (140
      pmol/rat) bilaterally microinjected into the Arc induced an significant
      inhibition of pentagastrin (PG) stimulated (16 mg/kg per h) gastric acid
      secretion throughout an observation period of 120 min after microinjection.
      Microinjection of kainate into hypothalamic areas outside the arcuate nucleus did
      not modify gastric secretion. Bilateral cervical vagotomy blocked the effect of
      kainate injected into the Arc on PG-stimulated gastric acid secretion. These data
      show that gastric secretory function can be modulated by stimulation of neuronal
      activity in the Arc via efferent vagal pathways. The results suggest that the
      arcuate nucleus is a forebrain area involved in the CNS regulation of
      gastrointestinal function.

PMID- 11532244
TI  - Contribution of vision and cutaneous sensation to the control of centre of mass
      (COM) during gait termination.
AB  - This study employed manipulation of sensory inputs (vision and plantar-surface
      cutaneous sensation) during gait termination to elicit insight into the roles
      played by these sensory systems in the control of gait termination. Attenuation
      of cutaneous sensation was achieved through hypothermic anesthesia. Visual
      information was occluded using special glasses. The subjects were asked to walk
      along an 8 m walkway and during randomly selected trials (25% of trials) to
      terminate their gait in a predetermined area. The centre of mass (COM) was
      obtained in order to provide an indication of the efficiency and stability during
      termination when sensory inputs were manipulated. Lack of visual information
      delayed the initiation of the slowing down of the COM forward progression and
      increased the step length of the last step of termination. Additionally, lack of
      vision resulted in the COM moving closer to the base of support (BOS) during
      double support and more variability, in the COM, when attempting to achieve a
      final stable position. Insensitivity of the plantar-surface mechanoreceptors led
      to a longer second step and a more variable foot placement of the first step, and
      increased the loading rate during the final two steps of termination.
      Additionally when vision and cutaneous information were absent the resolution of
      the final stable position was not as effectively controlled. The results
      demonstrated that visual information about self-motion and object-motion and
      sensation from the plantar surface of the foot play phase-specific roles in the
      control of COM during gait termination.

PMID- 11532243
TI  - Metabotropic glutamate 1alpha receptors on peripheral primary afferent fibers:
      their role in nociception.
AB  - Several lines of evidence indicate that Group I metabotropic glutamate (mGlu)
      1alpha receptors are involved in the processing of nociceptive information in the
      spinal cord. The goals of the present study are to document the role of
      mGlu1alpha receptors in peripheral nociception. To accomplish this we investigate
      the presence of mGlu1alpha receptors on peripheral primary afferent fibers and
      determine the behavioral effects of (S)-3,5-dihydroxyphenylglycine (S-DHPG),
      which is an mGlu1/5 receptor agonist and (RS)-1-aminoindan-1, 5-dicarboxylic acid
      (AIDA), a selective mGluR1alpha antagonist, on mechanical and thermal sensitivity
      and formalin-induced nociceptive behaviors. The anatomical studies at the
      electron microscopic level demonstrate that 32.4+/-2.9% of the unmyelinated axons
      and 21.6+/-4.7% of the myelinated axons are positively immunostained for
      mGlu1alpha receptors. Intraplantar injection of 0.1 or 1 mM S-DHPG results in a
      significant increase in mechanical sensitivity that persists for more than 60 min
      and this effect is blocked by co-injection of S-DHPG with 1 mM AIDA. Intraplantar
      injection of 40 microM AIDA+2% formalin significantly attenuates phase 2
      lifting/licking and flinching behavior and this AIDA-induced effect is blocked
      with co-injection of 1 microM S-DHPG. In behavioral tests, intraplantar S-DHPG
      (0.1, 1.0, 10 mM) does not change tail flick latencies or paw withdrawal
      latencies to heat stimulation. These data indicate that mGlu1alpha receptors are
      present on peripheral cutaneous axons and activation of peripheral mGlu1alpha
      receptors contributes to mechanical allodynia and inflammatory pain but not
      thermal hyperalgesia.

PMID- 11532245
TI  - Subdural engraftment of serotonergic neurons following spinal hemisection
      restores spinal serotonin, downregulates serotonin transporter, and increases
      BDNF tissue content in rat.
AB  - Spinal hemisection injury at T13 results in development of permanent mechanical
      allodynia and thermal hyperalgesia due to interruption and subsequent loss of
      descending inhibitory modulators such as serotonin (5-HT) and its transporter (5
      HT(T)). We hypothesize that lumbar transplantation of non-mitotic cells that
      tonically secrete 5-HT and brain-derived neurotrophic factor (BDNF) will restore
      alterations in 5-HT and 5-HT(T) systems within the spinal dorsal horn. We used an
      immortalized rat neuronal cell line derived from E13 raphe (RN46A-B14) which is
      shown to secrete 5-HT and BDNF in vitro and in vivo. Three groups (n=35) of 30
      day old male Sprague-Dawley rats were spinally hemisected at T13 and 28 days
      later received either lumbar RN46A-V1 control empty-vector (n=15) or RN46A-B14
      (n=15) intrathecal grafts, or no transplant. Twenty-eight days following
      transplantation, animals were perfused and tissue examined for changes in 5-HT, 5
      HT(T), and BDNF at the site of transplantation or at lumbar enlargements (L5).
      Immunohistochemistry revealed that RN46A-B14, but not RN46A-V1 cells, increased 5
      HT tissue staining at L5 in the dorsal white matter as well as in superficial
      dorsal horn laminae I and II on both ipsilateral and contralateral sides, results
      confirmed by ELISA. Transplantation of RN46A-B14 cells significantly reduced
      ipsilateral 5-HT(T), upregulated after injury. Significantly increased levels of
      BDNF were also observed after RN46A-B14 transplantation but were not localized to
      particular spinal laminae. These results are consistent with recovery of
      locomotor function and reductions in chronic pain behaviors observed behaviorally
      after RN46A-B14 transplantation and supports the pragmatic application of cell
      based therapies in correcting damaged circuitry after spinal cord injury.

PMID- 11532246
TI  - Distribution of TGF-beta, the TGF-beta type I receptor and the R-II receptor in
      peripheral nerves and mechanoreceptors; observations on changes after traumatic
      injury.
AB  - The mechanisms governing the regeneration of denervated peripheral
      mechanoreceptors are similar to those of peripheral nerves. The ability to
      regenerate depends partly on changes of the Schwann cell phenotype. The
      transforming growth factor beta (TGF-beta) family have been implicated in
      induction of Schwann cell proliferation, production of extracellular matrix and
      neurotrophin synthesis as well as synthesis or repression of cell adhesion
      molecules. Hence, they may prove to be of importance for regenerative mechanisms
      in peripheral mechanoreceptors. The distribution of TGF-beta, the receptors I and
      II and intra-cellular second messengers, Smad 2/3 and 4 was assessed in sensory
      neurones, peripheral nerves and mechanoreceptors by immuno-histochemistry, immuno
      electron microscopy and in situ hybridisation. TGF-beta2 mRNA and TGF-beta2-like
      immunoreactivity (IR) were expressed in injured small and medium sized rat
      sensory neurones of dorsal root ganglia. TGF-beta and receptor II mRNA and
      immunoreactivities (IR) were present in satellite cells. Intact and injured
      sensory neurones expressed receptor I mRNA and Smad 2 mRNA. TGF-beta2 mRNA was
      found in transected nerve stumps and in sensory mechanoreceptors. TGF-beta1, 2
      and Smad 4 were also observed in inner core lamellar cells of intact and
      denervated cat Pacinian corpuscles. Lamellar cells of intact and denervated
      Meissner corpuscles were TGF-beta immunoreactive. Merkel cells were receptors I
      and II immunoreactive. In conclusion, cutaneous and subcutaneous mechanoreceptors
      differ with regard to the expression of TGF-beta isoforms and receptors.

PMID- 11532247
TI  - Expression of endothelial and inducible NOS-isoforms is increased in Alzheimer's
      disease, in APP23 transgenic mice and after experimental brain lesion in rat:
      evidence for an induction by amyloid pathology.
AB  - The nitric oxide-synthesizing enzyme nitric oxide synthase (NOS) is present in
      the mammalian brain in three different isoforms, two constitutive enzymes (i.e.,
      neuronal, nNOS, and endothelial eNOS) and one inducible enzyme (iNOS). All three
      isoforms are aberrantly expressed in Alzheimer's disease giving rise to elevated
      levels of nitric oxide apparently involved in the pathogenesis of this disease by
      various different mechanisms including oxidative stress and activation of
      intracellular signalling mechanisms. It still is a matter of debate, however,
      whether the abnormal expression of NOS isoforms has some primary importance in
      the pathogenetic chain and might thus be a potential therapeutic target or only
      reflects a secondary effect that occurs at more advanced stages of the disease
      process. To tackle this question, we analysed the expression of both eNOS and
      iNOS in patients with sporadic AD, in transgenic mice expressing human amyloid
      precursor protein (APP) with the Swedish double mutation under control of the
      Thy1 promotor (APP23 mice), and after electrolytic cortical lesion in rat, an
      experimental paradigm associated with elevated expression of APP. In all three
      conditions, an astrocytosis was induced accompanied by a strong increase of both
      iNOS and eNOS. Both NOS isoforms were frequently though not always colocalized.
      Thus, based on the expression pattern of NOS isoforms three types of astrocytes,
      expressing only one of the two isoforms or both together could be distinguished.
      In both AD and transgenic mice eNOS-expressing astrocytes exceeded iNOS
      expressing astrocytes in number. Astrocytes with elevated levels of iNOS or eNOS
      were constantly seen in direct association with Abeta-deposits in AD and
      transgenic mice and were found in the vicinity of the lesion site in the rat
      cortex. The results of the present study show that expression of both iNOS and
      eNOS is increased in activated astrocytes under experimental conditions
      associated with elevated expression of APP (electrolytic brain lesion) or Abeta
      deposition (APP23 transgenic mice). Therefore, it is suggested that altered
      expression of these NOS isoforms being part of AD pathology is secondary to the
      amyloid pathology and might not be primarily involved in the pathogenetic chain
      though it might contribute to the maintenance, self-perpetuation and progression
      of the neurodegenerative process.

PMID- 11532248
TI  - Simultaneous activation and opioid modulation of long-term potentiation in the
      dentate gyrus and the hippocampal CA3 region after stimulation of the perforant
      pathway in freely moving rats.
AB  - Recent investigations indicate monosynaptic activation by the perforant pathway
      (pp) of the dentate gyrus and the CA3 region. While short-term potentiation and
      long-term potentiation (LTP) and its opioid modulation are frequently described
      for the dentate gyrus, data for the CA3 region are rare. Therefore, evoked
      potentials and opioid modulation of LTP were directly compared in both target
      regions of the pp. Male Wistar rats were chronically implanted with a bipolar
      stimulation electrode in the pp (angular bundle) and two recording electrodes in
      the dorsal dentate gyrus and the CA3 region. Stimulation of the pp in the freely
      behaving animals induced short-latency evoked potentials in both target
      structures which were compared with respect to waveform, latency, amplitude and
      signs of short- and long-term neuronal plasticity. The short-latency potential in
      the CA3 region seemed to be a monosynaptic potential which displayed LTP
      sensitive to the N-methyl-D-aspartate receptor antagonist, MK 801, and
      depotentiating stimulation. After application of specific opioid antagonists at
      the mu-, delta- and kappa-opioid receptor subtypes, naloxone, funaltrexamine,
      naltrindole and binaltorphimine, different effects on induction and maintenance
      of LTP of the population spike were found both within the dentate gyrus and
      between the dentate gyrus and the CA3 region. The results show marked diminution
      of LTP in the dentate gyrus only for naloxone and naltrindole and only small, if
      any, effects of naloxone on LTP in the CA3 region. Thus, neuronal plasticity in
      the direct perforant pathway input to the CA3 region seems not to be under such
      substantial opioidergic control. LTP would be inducible in that region even when
      LTP in the input formation, the dentate gyrus, and transsynaptic LTP via the
      mossy fibres are blocked.

PMID- 11532249
TI  - Inhibition of the ERK pathway prevents HIVgp120-induced REM sleep increase.
AB  - Approximately 35% of HIV-infected subjects, both children and adults, exhibit
      alterations in the sleep-waking cycle. HIV surface glycoprotein gp120 has been
      postulated to contribute to this abnormality. For example, it has been reported
      that HIVgp120 modifies sleep in freely-moving rats and that it also activates the
      ERK pathway in brain slices. The goal of this work was to determine if sleep
      changes induced by HIVgp120 in normal rats are mediated by the MAPK pathway. Our
      results show that a single intraventricular administration of HIVgp120
      selectively increases REMS and that such an increase can be prevented by U0126,
      an inhibitor of ERK activating enzyme, MEK. In contrast, SB202190, a MAPK-p38
      inhibitor, had no effect on HIVgp120-induced increase in REMS. These results
      suggest that HIVgp120 increases REMS in the rat by specifically affecting the ERK
      signal transduction pathway.

PMID- 11532250
TI  - Effects of chronic lesions of the anteroventral region of the third ventricle on
      cardiac beta-adrenoceptor function in conscious rats.
AB  - This study examined whether cardiac beta-adrenoceptor (beta-AR) function was
      altered in conscious rats with lesions surrounding the anteroventral third
      ventricle (AV3V). The findings were: (1) beta(1,2)-AR-mediated tachycardia was
      similar in sham and AV3V-lesion rats, (2) beta(3)- and/or atypical beta-AR
      mediated tachycardia elicited by isoproterenol (10 microg/kg, i.v.; ISO) was
      diminished in AV3V-lesion rats treated with beta(1,2)-AR antagonists, but was not
      in similarly-treated sham-lesion rats, and (3) the tachycardia elicited by the
      membrane permeable cAMP-analogue, 8-(4-chlorophenylthiol)-cAMP (10 micromol/kg,
      i.v.), was similar in AV3V- and sham-lesion rats. The possibility that increased
      plasma sodium/osmolality in AV3V-lesion rats down-regulated cardiac beta(3)-
      and/or atypical beta-ARs, but not beta(1,2)-ARs or intracellular cAMP signaling
      is discussed.

PMID- 11532251
TI  - Anti-TNF-neutralizing antibodies reduce pain-related behavior in two different
      mouse models of painful mononeuropathy.
AB  - We investigated the anti-hyperalgesic effect of neutralizing antibodies (AB) to
      tumor necrosis factor-alpha (TNF) in two murine models of neuropathy, the chronic
      constrictive sciatic nerve injury (CCI) which has a strong epineurial
      inflammatory component, and the partial sciatic nerve transection (PST), a 'pure'
      nerve injury model. In both models a single AB injection intra-operatively as
      well as on day 4 reduced thermal hyperalgesia significantly, whereas mechanical
      allodynia was only reduced with intraoperative but not with delayed treatment.

PMID- 11532252
TI  - Central mu opioid receptor mechanisms modulate mustard oil-evoked jaw muscle
      activity.
AB  - The injection of the small-fibre excitant and inflammatory irritant mustard oil
      (MO) into the temporomandibular joint (TMJ) region of rats evokes a sustained and
      reversible increase in electromyographic (EMG) activity of jaw muscles. The
      'rekindling' of this nociceptive reflex by intrathecal (i.t.) administration of
      the opiate antagonist naloxone and mu but not delta and kappa selective opioid
      antagonist, suggests that it may be modulated by endogenous opioid inhibitory
      mechanisms.

PMID- 11532253
TI  - Serum cleaved Tau protein and neurobehavioral battery of tests as markers of
      brain injury in experimental bacterial meningitis.
AB  - Brain injury due to bacterial meningitis affects multiple areas of the brain with
      a heterogeneous distribution generating a challenge to assess severity. Tau
      proteins are microtubular binding proteins localized in the axonal compartment of
      neurons. Brain injury releases cleaved Tau proteins (C-tau) into the
      extracellular space where they are transported to the cerebral spinal fluid. We
      hypothesized that C-tau crosses the blood-brain barrier during inflammation and
      that it can be detected in serum. The correlation between serum C-tau levels and
      the extent of the meningitic insult was examined. Furthermore, we studied whether
      the use of a subset of neurobehavioral tasks can assess the extent of brain
      injury after meningitis. The tests were chosen primarily for their ability to
      detect deficits in the acoustic system, low brain, reflexive responding, as well
      as for impaired motor coordination and the higher brain functions of learning and
      memory. A rat model of group B streptococcal meningitis with variable severity
      was utilized. At five days after bacterial inoculation followed by antibiotic
      therapy neurobehavioral tests were performed and serum C-tau and histologic
      samples of the brain were obtained. Our study shows that during meningitis C-tau
      appears in serum and reflects the extent of neurologic damage. Neurobehavioral
      performance was altered after bacterial meningitis and could be correlated with
      histologic and biochemical markers of neurologic sequelae. We conclude that serum
      C-tau and a composite of neurobehavioral tests could become useful markers for
      assessing the severity of neurological damage in experimental bacterial
      meningitis.

PMID- 11532276
TI  - The mannan-binding lectin pathway of complement activation: biology and disease
      association.
AB  - Mannan-binding lectin (MBL) is a plasma protein found in association with several
      serine proteases (MASPs) forming the MBL complex. MBL recognises carbohydrate
      structures arranged in a particular geometry, such as those found on the surface
      of micro-organisms. When bound to e.g. bacteria the MBL complex will initiate the
      activation of the complement cascade. Mounting evidence supports the importance
      of the MBL pathway of complement activation in innate immunity. In this review,
      we focus on the structure and function of the proteins within the MBL pathway and
      address the properties of the pathway as an initiator of the host response
      against potential pathogenic micro-organisms.

PMID- 11532254
TI  - Effects of hypocretin-saporin injections into the medial septum on sleep and
      hippocampal theta.
AB  - Neurons containing the peptide hypocretin, also known as orexin, were recently
      implicated in the human sleep disorder narcolepsy. Hypocretin neurons are located
      only in the lateral hypothalamus from where they innervate virtually the entire
      brain and spinal cord. This peptide is believed to be involved in regulating
      feeding and wakefulness. However, to fully understand what other behaviors are
      regulated by this peptide it is necessary to investigate each hypocretin target
      site. In the present study, we focus on one hypocretin target site, the medial
      septum, where there is a dense collection of hypocretin-2 receptor-containing
      cells, and degenerating axons are present here in canines with narcolepsy [J.
      Neurosci. 19 (1999) 248]. We utilize a saporin toxin conjugated to the hypocretin
      receptor binding ligand, hypocretin-2, and find that when this toxin is injected
      into the medial septum, it lesions the parvalbumin and cholinergic neurons. We
      contrast the effects of the hypocretin-saporin with another saporin conjugated
      toxin, 192 IgG-saporin, that lesions only the cholinergic neurons in the basal
      forebrain. 192 IgG-saporin reduced theta activity, a finding consistent with
      previous reports [J. Neurophysiol. 79 (1998) 1633; Neurodegeneration 4 (1995) 61;
      Neuroscience 62 (1994) 1033]. However, hypocretin-saporin completely eliminated
      hippocampal theta activity by day 12, indicating that parvalbumin-containing
      cells in the medial septum generate theta. The daily amount of sleep and
      wakefulness were not different between hypocretin-saporin, 192 IgG-saporin, or
      saline-treated rats. The homeostatic response to 12 h prolonged wakefulness was
      also not affected in hypocretin-saporin lesioned rats. These findings suggest
      that hypocretin neurons could facilitate theta generation during episodes of
      purposeful behavior by activating GABAergic neurons in the MS/VDB. In this way,
      hypocretin, which is implicated in feeding, energy metabolism and wakefulness,
      serves to influence cognitive processes critical for the animal's survival.

PMID- 11532277
TI  - Deposition of C3b/iC3b leads to the concealment of antigens, immunoglobulins and
      bound C1q in complement-activating immune complexes.
AB  - Complement activation by bound IgG in serum at physiological concentrations is
      reflected in the deposition of C3b/iC3b in the absence of antigenic expression of
      the IgG or of any bound C1q on the target. The aim of this study was to
      investigate the functional requirements for this phenomenon and to establish its
      relationship to a release or concealment of the antigens. Microtiter wells coated
      with IgG by direct adsorption or by binding of IgG antibodies to pre-adsorbed
      homologous antigen were incubated with serum or serum reagents at 37 degrees C.
      The complement reaction was analyzed by ELISA to quantitate bound or released
      reaction products, and the release of IgG from the coated microtiter wells was
      gauged radiometrically. In the presence of serum, rapid binding of C1q and C3b
      occurred and was soon followed by a rapid loss of C1q expression; C3b binding
      remained high. Loss of IgG paralleled that of C1q. The functional requirement for
      the reaction was restricted to the activation and deposition of C3b/iC3b but was
      dependent of the combined function of the classical and alternative complement
      pathways. The loss of the IgG antigen was solely the result of antigen
      concealment, whereas the loss of C1q was only partly so. In biological terms, the
      concealment of bound IgG and C1q may reflect mechanisms by which complement down
      regulates leukocyte responses stimulated by ligand-cell membrane receptor
      interactions.

PMID- 11532278
TI  - C1-inhibitor deficiency and angioedema.
AB  - C1-inhibitor deficiency can be inherited or acquired; both conditions lead to
      recurrent angioedema that can be life threatening when the larynx is involved
      (hereditary angioedema, HAE; acquired angioedema, AAE). The genetic defect is due
      to the heterozygous deficiency of C1-Inh that is transmitted as an autosomal
      dominant trait. Mutations causing HAE have been found distributed over all exons
      and splice sites of C1-Inh structural gene: only a few of them have been found
      more than once. Depending on DNA defect, C1-Inh is not transcribed, or not
      translated or not secreted. Finally, in 15% of HAE patients, an antigenically
      normal, but non-functional C1-Inh is present in serum (HAE type II). C1-Inh
      deficiency can be acquired, due to an accelerated consumption. Such an
      accelerated consumption can depend on circulating autoantibodies that bind C1-Inh
      causing its inactivation and catabolism; or to associated diseases, usually
      lymphoproliferative diseases, that consume C1-Inh with different mechanisms.
      Effective therapies can prevent or revert angioedema symptoms in C1-Inh
      deficiency, the main problem of this condition remaining misdiagnosis. The common
      knowledge that angioedema is an allergic symptom frequently prevents a correct
      diagnostic approach: C1-Inh deficiency goes unrecognized and the disease can
      still be lethal. Correct prophylactic treatment is based on attenuated androgens
      in HAE and on antifibrinolytic agents in AAE. Life threatening laryngeal attacks
      and severe abdominal attacks are effectively reverted, in both conditions, with
      C1-Inh plasma concentrate. A special remark to this treatment should be made for
      autoantibody-mediated AAE where very high doses can be needed depending on the
      rate of C1-Inh consumption.

PMID- 11532279
TI  - Anaphylatoxins and infectious and non-infectious inflammatory diseases.
AB  - In recent years a plethora of data has accumulated directing toward an important
      role of polypeptides C3a and C5a and its degradation product C5adesArg,
      summarized as anaphylatoxins (ATs), in microbial host defense and immune
      regulation. The ATs exert their various biologic functions by interacting with
      specific C3a- and C5a-receptors present on cells of myeloid origin, epithelial
      cells, smooth muscle cells as well as on activated B- and T-cells. Activation of
      AT receptors mediates signal transduction pathways triggering a variety of
      proinflammatory events. However, by interacting with the cytokine- and chemokine
      network C3a and C5a exhibit also anti-inflammatory properties. In this review the
      focus is on the pathogenetic role of the ATs in sepsis, immune complex disease,
      delayed type hypersensitivity and asthma. Discussed are data from animal models
      in which the ATs are blocked by specific C3a or C5a inhibitors or from mice with
      genetic deletions of the specific receptors of either C3a or C5a/C5adesArg.

PMID- 11532280
TI  - Human C-reactive protein: expression, structure, and function.
AB  - C-reactive protein (CRP) is an acute-phase protein featuring a homopentameric
      structure and Ca-binding specificity for phosphocholine (PCh). Expression of CRP
      is regulated mainly at the transcriptional level with interleukin-6 being the
      principal inducer of the gene during the acute phase. The crystal structure of
      CRP has been determined and the topology and chemical composition of its ligand
      binding site determined. The wide distribution of PCh in polysaccharides of
      pathogens and in cellular membranes allows CRP to recognize a range of pathogenic
      targets as well as membranes of damaged and necrotic host cells. CRP bound to a
      multivalent ligand can efficiently initiate the assembly of a C3 convertase
      through the classical pathway and thus decorate the surface of the ligand with
      opsonic complement fragments. However, the protein does not favor the formation
      of a C5 convertase and therefore, CRP-initiated complement activation does not
      mediate acute inflammatory reactions and membrane damage. CRP also interacts with
      Fc receptors on phagocytic cells and acts as an opsonin. Other CRP-initiated
      signals through interactions with neutrophil Fc receptors have an overall anti
      inflammatory effect. Thus, the main biological function of CRP appears to be host
      defense against bacterial pathogens and clearance of apoptotic and necrotic
      cells. Protection from lethal bacterial infection, from complement-induced
      alveolitis, and from endotoxemia has been confirmed in vivo using transgenic
      mice. Additional functions, including participation in atherogenesis and
      pathogenesis of myocardial injury after myocardial infarction have been reported.
      However, the weight of the evidence is that CRP like other acute-phase proteins
      is a component first line of innate host defense.

PMID- 11532281
TI  - Autoantibodies to complement components.
AB  - The complement system is a major component of innate immunity. Under normal
      conditions the contribution of the complement system is beneficial, but when
      inappropriately activated it may cause damage to the host and under certain
      conditions it may even be the target of an autoantibody response. Autoantibodies
      directed against individual complement components, convertases, complement
      regulators and complement receptors have been described. The presence of
      autoantibodies in individuals may be associated with manifestations of disease,
      but only for some autoantibodies have clear causal relations been described.
      Autoantibodies against complement components can even be present in healthy
      individuals, indicating that the development of pathology most likely requires
      the simultaneous action of multiple processes. Since autoantibodies against
      complement components may cause depletion of circulating complement levels,
      leading to a secondary complement deficiency, it is imaginable that this process
      leads to an increased susceptibility to infections. In the present review, we
      describe autoantibodies against complement components and their subsequent
      effects.

PMID- 11532282
TI  - Complement and apoptosis.
AB  - Apoptosis and necrosis are two forms of cell death characterized by distinct
      morphologies. Until recently, complement-mediated cell lysis has been presented
      as a classical example of necrotic cell death. However, recent reports on
      apoptogenic effects of complement have shaken this dogma. The field has become
      even more confusing with descriptions of anti-apoptotic effects of complement.
      Necrosis has been associated traditionally with inflammation, whereas apoptosis
      has been regarded as noninflammatory. Therefore, first descriptions of the
      capacity of the complement system to identify apoptotic cells and to be activated
      by them, led to the development of the concept that complement opsonizes
      apoptotic cells for fast clearance by phagocytic cells. In the absence of such
      opsonization, (eg in C1q or C4 deficiency), apoptotic cells may remain longer in
      the body and may stimulate autoantibody production or undergo pro-inflammatory
      secondary necrosis. This has been associated in man and mouse with the
      development of an autoimmune disease like systemic lupus erythematosus. However,
      complement may also interfere with the programmed intention of apoptosis to avoid
      triggering of inflammation. Our recent results show that, under specific
      conditions, early apoptotic cells are not only opsonized by complement but may
      also be lysed, raising the possibility that under certain conditions apoptosis
      will be associated with an inflammatory reaction. The review describes and
      discusses the reports covering the various aspects of the interface between
      complement and apoptosis and its possible relevance to autoimmune diseases and
      inflammation and raises the following questions: 1. Can activated complement
      proteins induce apoptotic cell death? 2. Can complement protect cells from
      apoptosis? 3. Do apoptotic cells activate complement? and 4. What role is
      complement playing in clearance of apoptotic cells and which complement receptors
      are involved? Clearly, this research field is highly complex and still at its
      formation stage, yet interesting and important mechanisms are bound to emerge
      from these studies.

PMID- 11532283
TI  - Extrahepatic synthesis of complement proteins in inflammation.
AB  - The demonstration of local complement protein synthesis leads to speculation as
      to the biological significance of this phenomenon. A narrative review is provided
      to illuminate several queries. It is difficult to establish a causal role for the
      locally produced complement because participation of systemic complement cannot
      be excluded. It is also difficult to discern whether local complement synthesis
      is a beneficial response to an inflammatory event or whether it promotes tissue
      damage. Finally, it remains to be seen if the roles of local and systemic
      complement differ in these respects. Extrahepatic expression of complement
      components of the activation pathways may provide a rapid response to microbial
      invasion. Once produced and activated, these proteins evoke a phlogistic response
      composed of cells and soluble mediators of inflammation. Many cells, not only
      synthesize complement proteins, but can also be stimulated via their complement
      receptors. This positive feedback may enhance local immune defense, especially in
      organs isolated from plasma components. In addition, local environmental factors
      in different organs may differentially regulate complement synthesis. These
      factors may include pro-inflammatory molecules and non-immune effectors, such as
      tissue ischemia/reoxygenation and drugs. Local complement dysregulation due to
      inhibition of activity of a complement regulatory component was shown to cause
      disease and restoration of the capacity to regulate the complement pathway
      restored health. Extrahepatic complement synthesis may also modulate local
      cellular responses, as to decrease detrimental damage of the inflammatory
      reaction. The demonstration that complement proteins play a significant role in
      the clearance of apoptotic cells suggests that local synthesis and activation of
      complement may contribute not only to tissue damage but also to tissue repair.

PMID- 11532284
TI  - Expression and regulation of complement factors H and I in rat and human cells:
      some critical notes.
AB  - The complement factors I (FI) and H (FH) are complement regulatory proteins. FI,
      a highly glycosylated serine protease of 88 kDa cleaves the alpha-chains of both
      complement components C3b and C4b, thereby inactivating them. Complement FH, a
      glycoprotein of 150 kDa which is composed of 20 short consensus repeats
      synergizes with FI by increasing the affinity of FI for C3b in the C3b/FH complex
      by about 15-fold as compared to free C3b. Furthermore, FH prevents factor B from
      binding to C3b and promotes the dissociation of the C3bBb complex. Both, FI and
      FH are mainly synthesized in the liver. According to the quantification of
      specific mRNA of both factors, various amounts are produced by different liver
      cell types, i.e. hepatocytes (HC) and Kupffer cells (KC). Investigations of
      cultured primary HC and KC from rat liver showed that FI is exclusively
      synthesized and secreted by HC whereas FH is synthesized by both HC and KC. Using
      quantitative-competitive PCR for the quantification of FH-specific mRNA, its
      constitutive rate of synthesis was found to be nearly ten times higher in KC than
      in HC. An extrahepatic source of both proteins are human umbilical vein
      endothelial cells (HUVEC) in which the synthesis of FI is upregulated by IL-6
      which is in accord with the upregulation observed in rat HC and two rat hepatoma
      cell lines (FAO and H4IIE). Three other proinflammatory cytokines, IL-1beta, IFN
      gamma and TNF-alpha, were alone or in combination, without any effect on the
      regulation of FI. This demonstrates that the regulation of FI is similar in HUVEC
      and HC. These results are in contrast to a previously described IFN-gamma
      mediated upregulation of FI in HUVEC and suggest, in accordance with other
      investigations on extrahepatic sources of FI (e.g. myoblasts), that IFN-gamma has
      probably no prominent role in the regulation of FI. Instead, IL-6 appears to be
      the main upregulating cytokine of FI mRNA and of FI protein synthesis in HC as
      well as in rat and human hepatoma cells and in HUVEC. Of note are experiments by
      others and us who could not identify FI-specific mRNA in peripheral blood-derived
      monocytes, granulocytes, or B- and T-cells of man or rat and in rat peritoneal
      macrophages. FI-specific mRNA could also not be detected in B- or T-cell lymphoma
      cells, whereas FH-specific mRNA was easily detectable in both human and rat
      monocytes, and in rat peritoneal macrophages. These data support the notion that
      FI in contrast to FH is not expressed by cells of the monocyte-macrophage lineage
      or by other leukocytes of peripheral blood, at least in the absence of additional
      stimulants.

PMID- 11532285
TI  - Complement-dependent control of viral dynamics in pathogenesis of human
      immunodeficiency virus and simian immunodeficiency virus infection.
AB  - Since the first contact with the host, human immunodeficiency virus (HIV)
      exploits the complement system to reach maximal spread of infection. HIV has
      adapted many strategies to avoid complement-mediated lysis and uses the
      opsonization with complement fragments for attachment to complement receptors
      (CR). From the pathogen's perspective, binding to CR-expressing cells is
      remarkably beneficial, bringing together virus and activated target cells that
      are highly susceptible to infection. Moreover, complement-mediated trapping on
      CR+ cells permits HIV to infect surrounding cells even in the presence of an
      excess of neutralizing antibodies. Thus, complement activation initiates the
      assumption of power over the host's immune system by HIV and thus augments viral
      spread and replication throughout the body. On the other hand, natural hosts of
      primate lentiviruses, such as sooty mangabeys, African green monkeys and
      chimpanzees, are generally considered to be resistant to the development of AIDS,
      despite persistent viral replication. This review focuses on the possible link
      between the resistance to disease and species-specific diversity in function of
      human and monkey complement system.

PMID- 11532286
TI  - Membrane-targeted complement inhibitors.
AB  - Undesirable complement activation contributes to the pathology of many human
      diseases by damaging tissue and promoting inflammation. Because complement
      mediated damage is caused by the deposition of complement components on the cell
      surface, several strategies have been devised to target complement regulator
      proteins to cell membranes. These strategies have resulted in engineered proteins
      that have improved potency in vitro and enhanced therapeutic benefit in animal
      models of disease. One membrane-targeted complement inhibitor has now entered
      clinical development and this class of second-generation agents may provide
      effective therapies for the treatment of a variety of disease states.

PMID- 11532308
TI  - Effect of PSC 833 liposomes and Intralipid on the transport of epirubicin in Caco
      2 cells and rat intestines.
AB  - Clinical applications of first-generation multidrug resistance (MDR) modulators,
      such as cyclosporin A (CsA) have been hampered because of their severe side
      effects in vivo. Recent investigations have led to the development of a more
      potent and less toxic modulator, PSC 833, which is a nonimmunosuppressive
      analogue of CsA. However, adverse pharmacokinetic interactions between anticancer
      drugs and PSC 833 have resulted in increased toxicity as compared to the
      individual toxicity. Our study evaluated the MDR reversing effect of PSC 833 in
      free, liposomal or Intralipid formulations on the uptake and transport of
      epirubicin in Caco-2 cells and everted gut sacs of rats. The results showed that
      PSC 833 in free or liposomal formulations significantly enhanced the
      intracellular accumulation of epirubicin in a dose-related manner in Caco-2
      cells. The optimum in enhancement was observed at the concentration of 2 microM
      PSC 833. These formulations markedly increased the apical to basolateral
      absorption of epirubicin in Caco-2 cells and substantially improved the mucosal
      to serosal absorption of epirubicin in rat jejunum and ileum. PSC 833 in free,
      liposomal or Intralipid formulations all significantly reduced basolateral to
      apical efflux of epirubicin across Caco-2 monolayers. However, PSC 833 in
      liposomes showed greater enhancement than other formulations. In conclusion, PSC
      833 and PSC 833 liposomes have the function as MDR reversing agents for the
      inhibition of intestinal P-glycoprotein. Liposomal preparations of PSC833 may
      provide a useful alternative dosage form for intravenous administration of PSC
      833 to be combined with anticancer drugs to circumvent drug resistance in cancer
      chemotherapy.

PMID- 11532309
TI  - Protein delivery from materials formed by self-selective conjugate addition
      reactions.
AB  - A new chemical cross-linking scheme was utilized for the formation of degradable
      poly(ethylene glycol) hydrogels suitable for the delivery of protein drugs. An
      aqueous solution containing a PEG-multiacrylate and solid particles of albumin
      was mixed with an aqueous solution containing a PEG-dithiol, rapidly producing a
      cross-linked hydrogel through a Michael-type addition reaction. For some
      formulations, it was observed that about 65% of the incorporated protein was
      released with zero-order kinetics over a period of about 4 days. By changing the
      functionality of the cross-linker, the release of protein could even be delayed
      for about 4 days, followed by zero-order release. The mechanism for release
      appeared to be a combination of slow dissolution of protein in the presence of
      PEG and hindered diffusion of protein through the gel. The cross-linking of the
      gels was studied rheometrically, and the hydrolytic degradation of the gels was
      characterized by measuring the swelling of the gels. Biochemical analysis of the
      released proteins demonstrated that the polymers reacted with each other, but not
      with proteins. Utilizing the Flory-Rehner and Peppas-Merrill equations, a
      framework for modeling the protein release from the gels is described.

PMID- 11532310
TI  - Temperature-controlled content release from liposomes encapsulating Pluronic
      F127.
AB  - Temperature-dependent internal content release from liposomes was examined using
      di-oleoylphosphatidylcholine (DOPC)/cholesterol liposomes with encapsulated
      Pluronic F127 molecules. The interaction of Pluronic F127 with the lipid bilayer
      at elevated temperature causes the release of encapsulated contents. Content
      release was measured using fluorescent markers of two different sizes: small,
      carboxyfluorescein (CF), and large, bovine serum albumin-conjugated fluorescein
      iso-thiocyanate (BSA-FITC). Release of CF was studied using fluorescence de
      quenching, while that of BSA-FITC was studied using fluorescence emission
      quenching due to fluorescence resonance energy transfer (FRET). Temperature
      controlled complete internal content release was achieved at a precise
      temperature by controlling the concentration of the encapsulated Pluronic.
      Increasing cholesterol % in the liposome composition resulted in a sharper
      transition with temperature in content release. The onset temperature of content
      release increased with decrease in Pluronic concentration. For the same Pluronic
      concentration, the onset temperature also depended on the size of the
      encapsulated marker and was higher for larger markers. We have established that
      onset of content release is determined by the critical micellar temperature (CMT)
      of the Pluronic. Temperature-sensitive liposomes, made stealth using di
      stearoyl(polyethylene glycol 5000) phosphatidylethanolamine (DSPEG5000PE) in
      conjunction with Pluronic F127, had similar temperature sensitivity and
      efficiency in content release compared to the non-stealth liposomes.

PMID- 11532311
TI  - Investigation of the influence of mean HPMC particle size and number of polymer
      particles on the release of aspirin from swellable hydrophilic matrix tablets.
AB  - The effects of hydroxypropyl methylcellulose (HPMC) of different particle size
      ranges, size distributions and concentrations on the release behaviour of aspirin
      from a swellable matrix tablet system were studied. A mean HPMC (Methocel K15M
      Premium) particle size of 113 microm was identified as a critical threshold in
      this study. Drug release rate increased markedly when polymer particle size was
      increased above 113 microm. Release rate was much less sensitive to changes in
      particle size below 113 microm. Aspirin release mechanism followed first order
      kinetics where mean HPMC particle size was below 113 microm. Release mechanism
      deviated from first order kinetics when the mean particle size was above 113
      microm. Polymer fractions with similar mean particle size but differing size
      distribution were also observed to influence drug release rate but not release
      mechanism. First order release constant K(1) was found to be quantitatively
      related to the reciprocal of the cube root of both mean polymer particle size and
      number of polymer particles in the matrix.

PMID- 11532312
TI  - Cross-linked high amylose starch derivatives as matrices for controlled release
      of high drug loadings.
AB  - Selection of hydrogels as excipients in controlled drug release systems depends
      on the characteristics of the gel and of the drug. Three types of derivatives
      were synthesized from cross-linked high amylose starch (HASCL-6) by substitution
      of hydroxylic groups with cationic (carboxymethyl: CM), anionic (aminoethyl: AE)
      and acetate (Ac) groups. These new polymeric excipients are able to control the
      release over 20 h from monolithic tablets loaded with 20 to 60% drug. Three drugs
      were used as model tracer: acetaminophen (uncharged), acetylsalicylic acid
      (having an acidic group) and metformin (having a basic group). It was found that
      the release of ionic drugs from CM-HASCL-6 and AE-HASCL-6 matrices can be
      partially controlled by ionic interaction between pendant groups of polymer and
      drugs. The substitution degree of HASCL-6 derivatives can also be varied to
      modulate the drug's release time. These derivatives represent a novel generation
      of pharmaceutical excipients, recommended for high loading dosage formulations.

PMID- 11532313
TI  - Evaluation of particle uptake in human blood monocyte-derived cells in vitro.
      Does phagocytosis activity of dendritic cells measure up with macrophages?
AB  - This work focuses on microparticles as potential antigen delivery systems to
      target professional antigen-presenting cells. Surface modified polystyrene
      microparticles were administered to human-derived macrophages (MPhis) and
      dendritic cells (DCs) in vitro to evaluate the phagocytosis activity of each cell
      type. To discriminate between internalised particles and those closely attached
      to the outside of the cells, particle internalisation was verified by confocal
      laser scanning microscopy. Especially positively charged particles tend to stick
      to the outer cell membrane and may lead to false positive results when measured
      by conventional microscopy. In contrast, fluorescence microscopy in combination
      with an extracellular fluorescence quenching agent (trypan blue) allows the
      unequivocal assessment of particle uptake for screening purposes. For this assay,
      the fluorescent label needs to be in direct contact to the quenching agent and
      cannot be localised inside the particle core. Different types of microparticles
      varying in size, surface-material and zeta potential resulted in vast differences
      regarding their uptake by MPhis and DCs as well as the maturation of DCs.
      Negatively-charged carboxylated and bovine serum albumin-coated particles were
      phagocytosed by MPhis to a relatively small extent. Interestingly, phagocytosis
      of these particles was still significantly lower in DCs while positively charged
      poly-L-lysine (PLL) coated particles induced high phagocytosis activity in both
      cell types. By comparing our results with literature data, we conclude that
      phagocytosis activity of DCs and MPhis largely depends on particle size and
      surface charge and is also influenced by the character of bulk and coating
      material. PLL can be directed to DCs and MPhis with comparable efficiency and, in
      addition, induce maturation of DCs.

PMID- 11532314
TI  - Piroxicam delivery into human stratum corneum in vivo: iontophoresis versus
      passive diffusion.
AB  - A nonsteroidal anti-inflammatory drug, piroxicam, was administered from a
      commercially available gel to human volunteers both passively and under the
      application of an iontophoretic current. The effect of occlusion on the passive
      delivery of piroxicam was also examined in a separate series of experiments.
      After treatment, the stratum corneum (SC) at the site of application was
      progressively tape-stripped and piroxicam transport into the membrane was
      assessed by UV-analysis of drug extracted from the tape-strips. Analysis of
      variance did not show any significant difference between passive piroxicam
      delivery after 30, 60 or 125 min. However, current application enhanced drug
      uptake into the SC, as indicated by both increased piroxicam concentrations in
      the horny layer and detectable concentrations at greater depths into the
      membrane. The total amount of drug recovered in the SC post-iontophoresis was
      significantly higher than that found following passive diffusion for each
      application time. The amounts of drug recovered from the tapes after 60 and 125
      min of current application were significantly higher than that after 30 min
      treatment. Finally, the in vivo SC concentration profiles following passive
      delivery were fitted to the appropriate solution of Fick's second law of
      diffusion to determine skin partitioning and diffusivity parameters.

PMID- 11532315
TI  - Toxicological evaluation of a bioadhesive nasal powder containing a starch and
      Carbopol 974 P on rabbit nasal mucosa and slug mucosa.
AB  - The purpose of this study is the investigation of possible adverse effects of a
      powder formulation containing drum-dried waxy maize (DDWM) starch and Carbopol
      974 P (90/10) on the nasal mucosa of rabbits and the foot mucosa of slugs after
      multiple administrations. In the rabbit, the effect of the formulation was
      measured by the release of proteins and lactate dehydrogenase (LDH) from the
      nasal mucosa with a new non-invasive in vivo method and also by histopathology.
      The mucosal toxicity of the formulation was evaluated using slugs by measuring
      the effect on the body weight and the amount of mucus produced during a repeated
      contact period. Additionally, the release of proteins, lactate dehydrogenase and
      alkaline phosphatase from the body wall of the slugs after a repeated treatment
      was measured. Twenty four hours after the powder administration to the rabbits
      the release of the marker molecules was comparable with the negative controls.
      The histopathological study showed only a slight increase of granulocytes in the
      epithelium. The formulation induced a higher mucus production in the slugs but no
      additional effects were detected on the body weight and on the release of
      proteins. No enzymes were released from the body wall. The results indicate that
      the effect of the bioadhesive powder consisting of DDWM/Carbopol 974 P (90:10,
      w/w) on the mucosa was negligible.

PMID- 11532316
TI  - Experimental determination of the theophylline diffusion coefficient in swollen
      sodium-alginate membranes.
AB  - In this paper attention is focused on the determination of the drug diffusion
      coefficient in a swollen polymeric membrane referring to a recent mathematical
      model (linear model). The main advantage deriving from its use is that, despite
      its analytical nature and its ability to account for the most important aspects
      characterising a permeation experiment, it can also be applied in the case of
      thick membranes. To check the model reliability, a comparison is made with a more
      complex numerical model and with a largely employed model in terms of data
      fitting quality. To this purpose, particular care is devoted to the experimental
      and theoretical tools employed to calculate the auxiliary parameters required by
      the three models, and with the aim of getting a drug diffusion coefficient value
      as accurate as possible. Theophylline was chosen as model drug owing to its wide
      employment in the pharmaceutical field. Membranes were prepared with sodium
      alginates hydrogels at three different polymer concentrations. The present
      analysis demonstrates the reliability of the linear model and reveals that the
      theophylline diffusion coefficient is not significantly affected by the polymer
      concentration. Indeed, such a parameter is reflected in different membrane
      thicknesses rather than in different mesh sizes of the polymeric network.

PMID- 11532317
TI  - Poly(ethylene glycol)-human serum albumin-paclitaxel conjugates: preparation,
      characterization and pharmacokinetics.
AB  - Paclitaxel has been found to be very effective against several human cancers,
      such as ovarian, breast and non-small cell lung cancer and has received marketing
      approval for metastatic cancers. One of main problems with its use is its poor
      solubility, which makes irritant solubilitazion agents necessary. In previous
      research we demonstrated that linkage to human serum albumin (HSA) was useful to
      increase the in vivo performance of paclitaxel. In this article, in order to
      improve stability and solubility of paclitaxel conjugate, we linked covalently a
      monomethoxy poly(ethylene glycol) (mPEG) chain to HSA. New thioimidate mPEG
      derivatives, highly reactive and stable, were used and two different conjugates
      (with PEG of molecular mass 2 or 5 kDa) were prepared, purified and
      characterized. The antitumor activity of the free drug and conjugates was tested
      on three different tumor cell lines. The PEG grafted conjugates maintained high
      cytotoxicity, similar to that of ungrafted conjugates, with efficient cell
      binding and internalization followed by release of the drug inside the cell. The
      changes in pharmacokinetics and distribution of radio-labelled conjugates were
      evaluated by i.v. administration to mice and compared with those of the free drug
      and ungrafted conjugates. The total clearance was reduced (from 3.6 ml/h for free
      drug to 2.9, 1.97 and 1.41 for ungrafted, 2 and 5 kDa PEG conjugates,
      respectively). Organ uptake was reduced, in particular by liver and spleen.

PMID- 11532318
TI  - Emulsions containing partially water-miscible solvents for the preparation of
      drug nanosuspensions.
AB  - The aim of this study was to investigate the feasibility of partially water
      miscible solvents, such as benzyl alcohol, butyl lactate and triacetin, to
      prepare drug nanosuspensions by a solvent quenching technique. Mitotane, which
      possesses very poor water solubility and low bioavailability, was used as model
      drug. Preparation was by emulsifying an organic solution of the drug in an
      aqueous solution of a stabilising agent followed by rapid displacement of the
      solvent from the internal into the external phase, provoking solid particle
      formation. To verify the influence of emulsion droplet size on the drug particle
      size, 0.1 or 0.2% of different emulsifiers (Tween 80, caprylyl-capryl glucoside
      or lecithin) and different homogenisation conditions (Ultra Turrax or a high
      pressure homogenizer at 200 or 1000 bar for three cycles) were used. In general,
      emulsion droplet size decreased with high pressure homogenization and on
      increasing the number of cycles. The size of drug particles, obtained after
      adding water at a constant rate, was dependent on the droplet size in the
      emulsion. Drug particles of approximately 80 nm were obtained using butyl
      lactate, supporting the hypothesis that drug particle formation by the
      emulsification diffusion process involves generating regions of local
      supersaturation. Because of the increase in available surface area, the
      dissolution rate of diaultrafiltrated suspensions increased greatly compared to
      commercial product.

PMID- 11532319
TI  - Dipeptide model prodrugs for the intestinal oligopeptide transporter. Affinity
      for and transport via hPepT1 in the human intestinal Caco-2 cell line.
AB  - The human intestinal di/tri-peptide carrier, hPepT1, has been suggested as a drug
      delivery target via increasing the intestinal transport of low permeability
      compounds by designing peptidomimetic prodrugs. Model ester prodrugs using the
      stabilized dipeptides D-Glu-Ala and D-Asp-Ala as pro-moieties for benzyl alcohol
      have been shown to maintain affinity for hPepT1. The primary aim of the present
      study was to investigate if modifications of the benzyl alcohol model drug
      influence the corresponding D-Glu-Ala and D-Asp-Ala model prodrugs' affinity for
      hPepT1 in Caco-2 cells. A second aim was to investigate the transepithelial
      transport and hydrolysis parameters for D-Asp(BnO)-Ala and D-Glu(BnO)-Ala across
      Caco-2 cell monolayers. In the present study, all investigated D-Asp-Ala and D
      Glu-Ala model prodrugs retained various degrees of affinity for hPepT1 in Caco-2
      cells. These affinities are used to establish a QSAR of our benzyl alcohol
      modified model prodrugs, aided at elucidating the observed differences in model
      prodrug affinity for hPepT1; additionally, these data suggest that the
      hydrophobicity of the side-chain model drug is the major determinant in the
      compounds affinity for hPepT1. Transepithelial transport studies performed using
      Caco-2 cells of D-Asp(BnO)-Ala and D-Glu(BnO)-Ala showed that the K(m) for
      transepithelial transport was not significantly different for the two compounds.
      The maximal transport rate of the carrier-mediated flux component does not differ
      between the two model prodrugs either. The transepithelial transport of D
      Asp(BnO)-Ala and D-Glu(BnO)-Ala follows simple kinetics, and the release of
      benzyl alcohol is pH-dependent, but unaffected by 1 mM of the esterase inhibitor
      Paraoxon in 80% human plasma and Caco-2 cell homogenate.

PMID- 11532320
TI  - Functional feature of a novel model of blood brain barrier: studies on permeation
      of test compounds.
AB  - Drug delivery to the central nervous system (CNS) is subject to the permeability
      limitations imposed by the blood-brain barrier (BBB). Several systems in vitro
      have been described to reproduce the physical and biochemical behavior of intact
      BBB, most of which lack the feature of the in vivo barrier. We developed a fully
      formed monolayer of RBE4.B immortalized rat brain microvessel endothelial cells
      (ECs), grown on top of polycarbonate filter inserts with cortical neuronal cells
      grown on the outside. Neurons induce ECs to synthesize and sort occludin to the
      cell periphery. Occludin localization is regulated by both compositions of the
      substratum and soluble signals released by cortical co-cultured neurons. The
      observed effects do not require strict physical contact among cells and neurons.
      To assess the physiological function of the barrier we examined the
      transendothelial transfer of three test compounds: dopamine, L-tryptophan and L
      DOPA. Polycarbonate filter inserts, where ECs were co-cultured with neurons, were
      assumed as open two compartments vertical dynamic models. Permeation studies
      demonstrated that the ECs/neurons co-cultures possess permeability
      characteristics approaching those of a functional BBB: the system behaved as a
      selective interface that excludes dopamine permeation, yet permits L-tryptophan
      and L-DOPA to cross. The movement of test compounds from the donor to the
      acceptor compartment was observed at a distinct time from the start of co
      culture. Transfer was determined using standard kinetic equations. Different
      performance was observed after 5 and 7 days of co-culture. After 5 days dopamine,
      L-tryptophan and L-DOPA passively permeate through the membrane as indicated by
      fittings with a first-order kinetic process equation. After 7 days of co-culture,
      occludin localizes at ECs periphery, dopamine does not cross the barrier to any
      further extent, while the transfer of L-tryptophan and L-DOPA fits well with a
      saturable Michaelis-Menten kinetic process, thus indicating the involvement of a
      specific carrier-mediated transport mechanism. Permeation studies confirmed that
      culture of ECs in the presence of neurons induces the characteristic permeability
      limitations of a functional BBB.

PMID- 11532321
TI  - Hydrophilic poly(DL-lactide-co-glycolide) microspheres for the delivery of DNA to
      human-derived macrophages and dendritic cells.
AB  - Biodegradable poly(lactide-co-glycolide) (PLGA) microspheres have a proven track
      record for drug delivery and are suggested to be ideal carrier systems to target
      therapeutics into phagocytic cells such as macrophages (MPhis) and dendritic
      cells (DCs). Microspheres prepared by spray-drying from different PLGA-type
      polymers were evaluated regarding their effect on phagocytosis, intracellular
      degradation and viability of human-derived macrophages MPhis and DCs. Even the
      microspheres prepared from the most hydrophilic polymer RG502H, were efficiently
      phagocytosed by primary human MPhis and DCs. Interestingly, uptake of PLGA
      microspheres by DCs as potent immune modulator cells was almost as efficient as
      uptake by the highly phagocytic MPhis. Phagocytosed microspheres remained inside
      the cells until decay with none of the microsphere preparations induced
      significant apoptosis or necrotic cell death. Acidic pH and the phagosomal
      environment inside the cells enhanced microsphere decay and release of
      encapsulated material. Degradation of microspheres consisting of the most
      hydrophilic PLGA polymer RG502H occurred in a reasonable time frame of less than
      2 weeks ensuring the release of encapsulated drug during the life span of the
      cells. To explore important technical and biological aspects of DNA
      microencapsulation, we have studied DNA loading and in vitro DNA release of
      microspheres from different PLGA type polymers. Hydrophobicity and molecular
      weight of the PLGA polymers had profound influence on both the encapsulation
      efficiency of DNA and its release kinetics in vitro: the hydrophilic polymers
      showed higher encapsulation efficiency and faster release of intact DNA compared
      to the hydrophobic ones. These results suggest that microspheres from the PLGA
      polymer RG502H have improved characteristics for DNA delivery to human MPhis and
      DCs.

PMID- 11532322
TI  - Stability of PEI-DNA and DOTAP-DNA complexes: effect of alkaline pH, heparin and
      serum.
AB  - DNA complexes formed with nonviral vectors such as polyethylenimine (PEI) or 1,2
      dioleoyl-3-trimethylammonium-propane (DOTAP) are widely used in gene therapy.
      These complexes prevent the interaction of DNA with the fluorescent probes
      usually employed to quantify DNA. We thus studied the procedures for DNA
      quantification from DNA complexes as well as their stability in the presence of
      DNase or mouse, rat and human sera. Release of the DNA from its complexes was
      accomplished by increasing the pH of the medium (from 7.3 to 13.4) or by adding
      heparin. The stability against degradation was tested in vitro, by incubating the
      complexes at 37 degrees C in the presence of DNase I and sera from the three
      species. Both high pH and heparin were able to release DNA from its complexes.
      Naked DNA formed aggregates with serum proteins that delayed electrophoresis
      migration, and this effect was reversed in the presence of heparin. However,
      these aggregates did not protect DNA from digestion by serum DNase, and the DNA
      digesting ability of serum was: mouse>rat>human. The DNA from the complexes was
      resistant to degradation by DNase I, although a low proportion of DNA from the
      complexes was partially digested, as determined by electrophoresis. In contrast,
      PEI-DNA and DOTAP-DNA complexes were stable in the presence of all sera. Heparin
      and high pH release DNA from its complexes. The order of DNA degradation is:
      mouse>rat>human, but DOTAP and PEI avoid degradation of DNA by serum compounds.

PMID- 11532323
TI  - A new gene delivery formulation of polyethylenimine/DNA complexes coated with PEG
      conjugated fusogenic peptide.
AB  - A fusogenic peptide, KALA, was conjugated with poly(ethylene glycol) (PEG) for
      use as an endosome disruptive agent in the gene delivery formulation of
      polyethyleneimine (PEI). A maleimide terminated methoxy-PEG, a cysteine specific
      derivative, was reacted with KALA to produce a PEG-KALA conjugate. The conjugate
      was analyzed by matrix-assisted laser desorption ionization time-of-flight mass
      spectrometry, and its hemolytic activity was determined relative to KALA.
      Positively charged PEG-KALA conjugate was coated onto the surface of negatively
      charged DNA/PEI complexes to form net positively charged PEG-KALA/DNA/PEI
      complexes. They were 200-400 nm in diameter with increasing amount of PEG-KALA,
      whereas DNA/PEI complexes coated with KALA aggregated to a great extent. This was
      because PEG chains surrounding the surface of the complexes suppressed the inter
      particle interaction that was mediated by cationic KALA. Transfection efficiency
      progressively increased as the amount of PEG-KALA to be coated was increased,
      suggesting that fusogenic activity of KALA contributes to enhancing the level of
      gene expression.

PMID- 11532324
TI  - The biomechanical integrity of bone in experimental diabetes.
AB  - Patients with diabetes mellitus incur a higher incidence of fractures compared to
      healthy individuals. This suggests that the structural integrity of the skeletal
      system may be compromised. To examine the biomechanical consequences of diabetes,
      we studied the structural integrity of the femur and tibia of rats with
      streptozotocin-induced diabetes. The induction of diabetes was confirmed by
      measuring blood glucose levels (>300 mg/dl). Seven-weeks following the
      establishment of diabetes, the animals were euthanized and the hind limbs
      removed. The femur and tibia of each hind limb were excised, and prepared for
      three point bending test on an Instron Materials Testing System. The results
      revealed a 37% decrease in maximum load (breaking strength) of the femur of
      diabetic rats when compared to controls. The diabetic femurs had 25% less
      deformation at maximum load compared to controls. Similarly, energy absorption
      capacity to yield point and toughness were reduced by 27 and 34%, respectively,
      in the diabetic femur. A 38% increase in the bending stiffness was observed in
      the femurs of diabetic rats. Similar results were obtained with the tibias of
      both groups. Measurement at the break point revealed that the bones of diabetic
      rats bore significantly less load, deformation and energy absorption capacity
      than controls. Overall, our findings warrant the conclusion that the diabetic
      state is associated with mechanical deterioration of bone, resulting in bones
      with inferior biomechanical integrity.

PMID- 11532325
TI  - Characteristics of type 2 diabetic patients responding to voglibose
      administration as an adjunct to sulfonylurea.
AB  - In this study, we characterized type 2 diabetic patients responding well to the
      alpha-glucosidase inhibitor voglibose administration as an adjunct to
      sulfonylurea treatment. Thirty-three type 2 diabetic patients were enrolled in an
      open prospective study. All the patients had been treated for at least 1 year
      with a sulfonylurea drug, in whom HbA1c level had been stable for at least 12
      weeks. The patients were given voglibose at a dose of 0.2 mg t.i.d. for 12 weeks.
      Voglibose administration significantly decreased the mean HbA1c level in all the
      patients at 4, 8, and 12 weeks. Twelve (36%) of the study patients were
      responders, when the responders were defined as patients whose HbA1c level at 12
      weeks fell by at least 1.0% from baseline, or those whose HbA1c level at 12 weeks
      was < or =7.0%, falling by at least 0.5% from baseline. The baseline fasting
      plasma glucose (FPG) was significantly lower, and the baseline homeostasis model
      assessment (HOMA) beta-cell function (HOMA-%beta) was significantly higher in the
      responders than in the non-responders. There were more patients who had FPG <170
      mg/dl and/or HOMA-%beta > or =30% in the responders than in the non-responders
      (P<0.005). None of the patients with both FPG > or =170 mg/dl and HOMA-%beta >30%
      responded to the adjunct treatment. These results indicate that baseline FPG and
      HOMA-%beta are useful clinical markers to predict the effectiveness of the
      adjunct therapy of voglibose in sulfonylurea-treated type 2 diabetic patients.

PMID- 11532326
TI  - Self-treatment of hypoglycemia while driving.
AB  - OBJECTIVE: While it is clear that progressive diabetic hypoglycemia leads to
      neuroglycopenia, which impairs driving, it is not clear what contributes to
      patients' detection and subsequent self-correction of hypoglycemia/driving
      impairments. Drivers with Type 1 Diabetes Mellitus (T1DM) who did and did not
      engage in self-treatment during experimental hypoglycemia driving are compared
      physiologically and psychologically. METHOD: 38 drivers with T1DM drove a
      sophisticated driving simulator during euglycemia and progressive hypoglycemia.
      Subjects were continually monitored for driving performance, EEG activity and
      whether they self-treated with a glucose drink. Every 5 min measures were taken
      of blood glucose (BG) and epinephrine levels, perceived neurogenic and
      neuroglycopenic symptoms and driving ability. For the four weeks prior to this
      hospital study, subjects participated in a field study. Using a hand-held
      computer just prior to routine self-measurements of BG, subjects rated neurogenic
      and neuroglycopenic symptoms and made judgements about BG level and ability to
      drive as they did in the hospital. RESULTS: Drivers who did and did not self
      treat did not differ in terms of their pre-hospital exposure to hypoglycemia,
      their depth and rate of BG fall during experimental testing, or their epinephrine
      response to hypoglycemia. Subjects who self-treated detected more neurogenic and
      neuroglycopenic symptoms than those who did not self-treat. They also experienced
      less EEG defined neuroglycopenia during the progressive hypoglycemic drive as
      compared to those who did not self-treat. Perceived need to self-treat and EEG
      parameters correctly classified 88% of those who did treat from those who did not
      self-treat. Further, subjects who self-treated were more aware of hypoglycemia
      and when not to drive while hypoglycemic in the field study. CONCLUSION: There is
      a narrow window between a patient's detection of hypoglycemic symptoms and the
      need to self-treat, and neuroglycopenia, which impairs self-treatment.
      Consequently, drivers with T1DM should be vigilant for signs of hypoglycemia and
      driving impairment (e.g. trembling, uncoordination, visual difficulties) and
      encouraged to treat themselves immediately when they suspect hypoglycemia while
      driving.

PMID- 11532327
TI  - GAD65 antibody prevalence and association with thyroid antibodies, HLA-DR in
      Chinese children with type 1 diabetes mellitus.
AB  - Persistent humoral autoimmunity to the enzyme glutamic acid decarboxylase (GAD)
      has been described in a substantial proportion of patients with type 1 diabetes
      mellitus. Higher prevalence of GAD antibody in diabetes patients using a new
      radioligand-binding assay with recombinant human GAD65 antibodies (GAD65Ab) has
      been seen in several studies. Using this method, we have reassessed the
      prevalence of GAD65Ab and investigated the association of GAD65Ab with HbA1C
      values, C-peptide values, HLA-DR typing and thyroid autoimmune antibody in 70
      Chinese children with type 1 diabetes mellitus (mean age of onset 8.21+/-3.84
      years, mean duration 3.39+/-2.54 years). Our result revealed that GAD65
      antibodies were present in 54.3% (38/70) of diabetes children. There was no
      significant difference in gender, diabetes onset and duration, HbA1c, C-peptide
      concentration and frequencies of HLA DR3, DR4, DR9, DR3/DR4, DR3/DR9 and DR4/DR9
      genotypes between GAD65Ab+ and GAD65Ab- groups. There was no negative correlation
      between GAD65Ab values and duration of diabetes in those with GAD65Ab positivity
      (r=-0.239, P>0.05). The frequencies of antimicrosomal and anti-thyroglobulin
      antibodies in GAD65Ab+ (13.5,8.1%, respectively) were not different from GAD65-
      patients (9.4,12.5%, respectively).

PMID- 11532328
TI  - Decreased nitric oxide end-products and its relationship with high density
      lipoprotein and oxidative stress in people with type 2 diabetes without
      complications.
AB  - Diabetes mellitus is associated with hyperglycaemia, hyperlipoproteinaemia,
      increased oxidative stress and decreased nitric oxide production from endothelial
      cells. In the present study the aim was to determine the relationships between
      serum lipids, lipoproteins, erythrocyte malondialdehyde (eMDA), as a marker for
      oxidative stress, and serum nitrite and nitrate levels, as degradation products
      of nitric oxide in type 2 diabetic patients without complications. The study
      group included 30 patients and 30 sex- and age-matched healthy volunteers. Total
      cholesterol, triacylglycerol, LDL cholesterol, apo B, HbA(1c) and glucose levels
      in patients were significantly higher than in controls, and HDL cholesterol
      levels lower. Increased eMDA levels and decreased nitrate and nitrite+nitrate
      levels (+/-SD) were observed in patients compared to controls (87+/-22 vs 59+/-17
      nmol/g-Hb (P<0.01); 11.8+/-8.6 vs 22.8+/-10.8 micromol/l (P<0.01); and 16.8+/
      11.0 vs 28.8+/-11.3 micromol/l (P<0.01), respectively). When the patients were
      divided into two groups according to HDL cholesterol levels (< or =0.91 and >0.91
      mmol/l), total plasma nitric oxide end-products were found to be decreased in
      patients with low HDL levels compared to those patients with high HDL levels
      [men, 11.7+/-6.4 vs 24.6+/-14.9 micromol/l (P<0.01); women, 12.5+/-6.6 vs 21.4+/
      6.6 micromol/l (P<0.01]. Nitrite and nitrate levels were correlated with HDL
      cholesterol (r=0.50, P<0.05) and eMDA (r=-0.52, P<0.05). It was concluded that
      the patients with unregulated blood glucose levels have abnormal lipid and
      lipoprotein metabolism and decreased nitric oxide end-products, with
      relationships between nitric oxide products and dyslipidaemia, especially between
      low HDL cholesterol levels and increased oxidative stress.

PMID- 11532329
TI  - A questionnaire for neurological symptoms in patients with diabetes--cross
      sectional multicenter study in Saitama Prefecture, Japan.
AB  - This study was designed to investigate the prevalence of neurological symptoms in
      diabetic patients living in Saitama Prefecture, Japan using 13-item
      questionnaire. A total of 6472 outpatients with diabetes (3417 men and 3055
      women) were recruited from 100 centers. Mean age and mean disease duration were
      60.9-year old and 10.4 years, respectively. The questionnaire for monitoring of
      neurological symptoms was completed at the clinic or hospital visited, and
      Achilles' tendon reflex, ophthalmologic, blood and urinary examinations were also
      performed. Of the 6472 patients, 84.8% suffered from a mean of 3.3+/-2.2
      neurological symptoms. However, half of these symptoms were not considered to be
      those of diabetic neuropathy by attending physicians. "Feeling as if a piece of
      paper is attached to the sole of the foot," "stinging and prickling sensations in
      feet," and "pain in feet" were the most common symptoms of diabetic neuropathy.
      The prevalence of diabetic neuropathy as determined by attending physician
      increased with disease duration and worse control of diabetes. This study found
      that the majority of diabetics were suffered from neurological symptoms, although
      half of such symptoms were not considered to be those of diabetic neuropathy by
      physicians. Furthermore, it is important for diabetics to be diagnosed and
      treated earlier to prevent progression to severe neuropathic complications by
      means of optimal glycemic control and use of some chemicals such as aldose
      reductase inhibitor, and to develop this study to evaluate the efficacy of
      treatments.

PMID- 11532330
TI  - Beta(3)-adrenergic receptor gene variant is associated with upper body obesity
      only in obese Japanese-American men but not in women.
AB  - We investigated gender differences in the relationships between the Trp64Arg
      variant of the beta(3)-adrenergic receptor (AR) gene in obesity and insulin
      resistance in nondiabetic subjects. In 476 nondiabetic Japanese-Americans
      (M/F=204/272), the Trp64Arg variant of the beta(3)-AR gene was examined. The
      presence or absence of the Trp64Arg mutation was examined in DNA separated from
      leukocytes in peripheral blood using the PCR-RFLP method. The frequency of
      abnormal allele of the beta(3)-AR gene was 0.18 for males and 0.17 for females,
      almost the same as the reported values in Japanese. There was no difference in
      the frequency of the beta(3)-AR gene variant between obese and non obese subjects
      for each gender. However, among obese males (body mass index > or =24.2 kg/m(2)),
      with the beta(3)-AR gene mutation, the waist-to-hip ratio, fasting insulin, 2-h
      insulin, total insulin, and HOMA, an index of insulin resistance, were all
      significantly higher than obese males without the mutation. In females, the index
      of obesity, insulin resistance, or lipid metabolism did not differ significantly
      between the subjects with or without the beta(3)-AR gene variant either in the
      obese and non-obese group. We suggest that the beta(3)-AR gene variant is not
      important as an obesity-inducing factor in Japanese. However, in males, when
      obesity becomes obvious, the beta(3)-AR gene variant is considered to influence
      the enhancement of insulin resistance, in association with visceral obesity.

PMID- 11532331
TI  - A suspected case of proximal diabetic neuropathy predominantly presenting with
      scapulohumeral muscle weakness and deep aching pain.
AB  - A 48-year-old man with a 14-year history of type 2 diabetes with proliferative
      diabetic retinopathy and distal symmetrical diabetic polyneuropathy visited our
      hospital. Eight months later, he subacutely developed difficulty in both shoulder
      movement and trouble standing up from a squatting position. This was accompanied
      by severe bilateral shoulder and thigh pain. Magnetic resonance imaging of the
      brain, cervical and lumbar spine, computed tomography of the shoulder and X-ray
      films of the cervical spine and shoulder revealed no abnormality. Cerebrospinal
      fluid showed a mild elevation of protein (0.93 g/l) without cell infiltration.
      Antiganglioside antibodies and point mutation of mitochondrial DNA at position
      3243 were not found. Neuropathology of the sural nerve showed a moderate
      myelinated fiber loss, active axonal degeneration, but onion-bulb formation,
      endoneurial or epineurial vasculitis were not observed. Electromyography revealed
      neurogenic changes in the proximal upper limb muscles. Nerve conduction studies
      revealed mild bilateral slowing in nerve conduction velocity in both of the upper
      and lower limbs. The diagnosis of this patients was suspected to be a proximal
      diabetic neuropathy (diabetic amyotrophy). The pain and muscle weakness had
      persisted more severely in the shoulder than in the thigh throughout the clinical
      course. His unbearable symptoms could be partially alleviated by an
      administration of a selective serotonin reuptake inhibitor, fluvoxamine maleate.
      Proximal diabetic neuropathy is a rare disabling type of neuropathy, which is
      characterized with subacute bilateral muscle weakness and wasting in the proximal
      part of the lower limbs. The involvement of the scapulohumeral region observed in
      this case is very unusual in proximal diabetic neuropathy.

PMID- 11532332
TI  - 3,4-Dihydroxyphenylacetaldehyde and hydrogen peroxide generate a hydroxyl
      radical: possible role in Parkinson's disease pathogenesis.
AB  - 3,4-Dihydroxyphenylacetaldehyde (DOPAL) and 3,4-dihydroxyphenylglycolaldehyde
      (DOPEGAL), the monoamine oxidase (MAO) metabolites of dopamine (DA) and
      norepinephrine (NE), respectively, are toxic to catecholamine (CA) neurons in
      vitro and in vivo. DOPEGAL generates a free radical and activates mitochondrial
      permeability transition, a mechanism implicated in neuron death. To determine if
      DOPAL and other DA metabolites generate the hydroxyl radical in the presence of
      H(2)O(2), we used HPLC-EC to detect salicylate hydroxylation products. To
      determine the relative reducing capacity of DOPAL and DOPEGAL we used cyclic
      voltammetry to measure their reduction potentials. Results indicate that DOPAL,
      but not DOPEGAL, DA or other DA metabolites, generates hydroxyl radicals. Atomic
      absorption spectroscopy and heavy metal screening indicate that this result is
      not due to contamination of DOPAL with iron or other heavy metals. DOPAL
      reduction potential (161 mV) is lower than that of DOPEGAL (235 mV). DOPAL is
      present in human substantia nigra. The implications of these findings to CA
      neuronal death in degenerative brain diseases are discussed.

PMID- 11532333
TI  - Involvement of non-NMDA receptors in the rescue of weaver cerebellar granule
      neurons and sensitivity to ethanol of cerebellar AMPA receptors in oocytes.
AB  - The cellular mechanism responsible for the death of cerebellar granule neurons in
      the weaver mutant mouse is still being intensely investigated. To determine if
      alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate
      receptors are involved in producing the weaver phenotype or are altered by the
      weaver gene, we used (1) reverse transcription and polymerase chain reaction (RT
      PCR) to detect transcripts of glutamate receptors (GluR1-4) from wild-type and
      mutant cerebella; (2) immunocytochemistry to establish the types of glutamate
      receptors present in granule neurons cultured from normal and homozygous weaver
      postnatal day 5-6 (P5-6) cerebella; (3) 6-cyano-7-nitroquinoxaline-2,3-dione
      (CNQX), a blocker of glutamate (AMPA/Kainate/NMDA) receptors, and 6,7
      dinitroquinoxaline-2,3-dione (NBQX), a blocker of AMPA and kainate receptors, to
      assess the number of neurons and the number of neurons with long neurites in
      cultures of homozygous weaver granule neurons; (4) two-electrode voltage clamp
      recordings to study AMPA glutamate receptor expression in Xenopus oocytes after
      injection of mRNA isolated from cerebella of normal and weaver P5-6, postnatal
      day 10 (P10) and postnatal day 23 (P23) mice; and (5) ethanol, which at low 1-10
      mM concentrations had been shown previously to rescue homozygous weaver granule
      neurons in culture [Liesi et al., J. Neurosci. Res. 48 (1997) 571-579], to
      examine its effect on modulation of AMPA receptors expressed from mRNA. By RT
      PCR, the mRNA coding for AMPA receptor subunits GluR1-4 were detected from +/+
      and wv/wv cerebella, and by immunocytochemistry, GluR1, GluR2/3 and GluR4 were
      observed to be expressed in cultured +/+ and wv/wv granule cells. CNQX at 10
      microM or NBQX at 10 microM significantly increased the number of surviving
      neurons and the number with long neurites as compared to wv/wv controls. In
      addition, CNQX was significantly more effective than NBQX. In oocytes injected
      with mRNA from P10 normal or weaver cerebella, the amplitudes of the responses to
      kainate were about equal. In contrast, the amplitudes of the kainate-activated
      currents in oocytes injected with weaver P23 mRNA were about twice as large as
      the currents observed in oocytes injected with mRNA from normal P23 cerebella,
      and both were larger than kainate-activated currents observed after injection of
      P10 normal and weaver mRNA. Kainate-activated AMPA receptor currents in oocytes
      injected with mRNA from P10 and P23 normal and homozygous weaver cerebella were
      inhibited by ethanol. There were no significant differences in the inhibition
      produced by ethanol on currents from P10 or P23 normal and wv/wv mRNA. Thus, P23
      weaver cerebellar mRNA expressed more kainate-activated current in oocytes than
      P23 normal cerebellar mRNA; both normal and weaver cerebellar granule neurons
      express mRNA coding for functional AMPA receptors that are susceptible to ethanol
      inhibition.

PMID- 11532334
TI  - Bcl-2 blocks cisplatin-induced apoptosis by suppression of ERK-mediated p53
      accumulation in B104 cells.
AB  - Bcl-2 has been reported to inhibit neurotoxicity induced by cisplatin. However,
      neither the mechanism of cisplatin-induced neurotoxicity nor the mechanism by
      which Bcl-2 confers neuroprotection is clear. In this study, the signaling
      pathways involved in cisplatin-induced neurotoxicity were examined using a rat
      neuroblastoma cell line, B104. Treatment of B104 cells with cisplatin induced
      apoptosis, accompanying the accumulation of p53 and Bax protein. Interestingly,
      extracellular signal-regulated kinase 1/2 (ERK1/2) activities of MAP kinases were
      markedly enhanced prior to cisplatin-induced accumulation of p53 and Bax.
      Inhibition of ERK1/2 activities using PD98059, a selective MEK inhibitor, blocked
      the apoptotic cell death preventing cisplatin-induced accumulation of p53 and
      Bax. These results suggest that ERK mediates cisplatin-induced p53 activation to
      trigger apoptosis in B104 cells. Overexpression of Bcl-2 in B104 cells resulted
      in the complete resistance to cisplatin-induced apoptosis blocking ERK activation
      and the subsequent signaling pathway of p53. Our study clearly demonstrates that
      the action site of Bcl-2 localizes upstream of ERK in cisplatin-induced apoptotic
      signaling pathway.

PMID- 11532335
TI  - Kappa opioid receptor stimulation decreases amphetamine-induced behavior and
      neuropeptide mRNA expression in the striatum.
AB  - The purpose of this study was to investigate the role that kappa opioid receptor
      stimulation has upon stimulant-induced behavior and neuropeptide gene expression
      in the striatum. Acute administration of amphetamine (2.5 mg/kg i.p.) caused an
      increase in behavioral activity and preprodynorphin, substance P, and
      preproenkephalin mRNA expression. When amphetamine-treated rats were pretreated
      with U69593, a kappa agonist (0.16 or 0.32 mg/kg s.c.), there was a significant
      decrease in behavioral activity. Quantitative in situ hybridization
      histochemistry revealed that 0.32 mg/kg U69593 significantly decreased
      amphetamine-induced mRNA expression of all three neuropeptides; however, only the
      induction of preproenkephalin mRNA was decreased by 0.16 mg/kg. These data
      suggest that stimulation of kappa receptors decreases acute amphetamine-induced
      behavior and mRNA expression of neuropeptides in the rat striatum.

PMID- 11532336
TI  - Expression of receptor-activity modifying protein (RAMP) mRNAs in the mouse
      brain.
AB  - Receptor activity modifying proteins (RAMPs) comprise a family of accessory
      proteins for G protein-coupled receptors (GPCRs). They function as receptor
      modulators that determine the ligand specificity of receptors for calcitonin gene
      related peptide (CGRP), amylin and adrenomedullin (ADM). Here we demonstrate for
      the first time the characteristic distributions of the RAMP family mRNAs in the
      brain. Northern blot analysis revealed that mRAMP 1 and 3 mRNAs were intensely
      expressed in the brain, but mRAMP2 mRNA less abundantly. In situ hybridization
      studies showed the heterogenous and unique distributions of mRAMP mRNAs; RAMP1
      mRNA was widely expressed throughout the brain including the cerebral cortex,
      caudate putamen, amygdaloid complex, hippocampus, cerebellum and ependyma, mRAMP2
      was most abundant in the hippocampus, cerebellum, pia mater and blood vessels,
      while mRAMP3 was specifically distributed in a variety of thalamic nuclei and the
      cerebellum. In addition, RAMP1 and -3 genes were also detected in the subfornical
      organ and area postrema, which are members of circumventricular organs lacking
      blood-brain barrier. The present results help in understanding the
      diversification and regulation of receptor functions for calcitonin family
      peptides, and potentially other GPCRs in the brain.

PMID- 11532337
TI  - Early postnatal ethanol exposure selectively decreases BDNF and truncated TrkB-T2
      receptor mRNA expression in the rat cerebellum.
AB  - Binge-like ethanol exposure on postnatal day (PN) 4 induces a concentration
      dependent loss of Purkinje cells in the rat cerebellum. The mechanism of this
      ethanol-induced Purkinje cell vulnerability is not presently understood.
      Nevertheless, the specific timing of this vulnerability leads us to consider the
      neurotrophin system crucial to the regulation of neuronal development.
      Differentiation, maturation, and survival of Purkinje cells are shown to involve
      an intimate interaction between brain-derived nerve growth factor (BDNF) and
      neurotrophin-3 (NT3) acting primarily through their specific tyrosine-kinase
      (Trk) receptors. We believe that the specific ethanol vulnerability, and the
      timing of this vulnerability result from alterations in the BDNF-NT3 interplay.
      We hypothesize that disruption of TrkB and/or TrkC mediated neurotrophin
      communication is, in part, responsible for the ethanol-induced loss of Purkinje
      cells during development. The current study was undertaken to define the impact
      of ethanol exposure at the onset of ethanol vulnerability on the relative
      concentrations of mRNA encoding the neurotrophic factor receptors TrkB and TrkC.
      The reverse transcriptase (RT) polymerase chain reaction (PCR) amplification
      technique was used to identify the relative expression levels of mRNA specific to
      these receptors as well as the truncated TrkB receptor isoforms. We identify a
      specific decrease in overall TrkB receptor mRNA expression that is primarily a
      function of the TrkB-T2 receptor isoform. Concurrent decreases in mRNA specific
      to BDNF were also identified. No significant alterations to the expression of
      TrkC mRNA were found indicating that ethanol-exposure appears to act selectively
      on the BDNF communication system.

PMID- 11532338
TI  - Serotonergic cells of the rat raphe nuclei express mRNA of tyrosine kinase B
      (trkB), the high-affinity receptor for brain derived neurotrophic factor (BDNF).
AB  - Here we have studied the distribution of mRNA for tyrosine kinase B (trkB), the
      high-affinity receptor for brain-derived neurotrophic factor (BDNF) amongst
      serotonergic cell bodies of the raphe nuclei and their ascending projections into
      the dorsal hippocampus in the rat brain. Previous studies have shown that BDNF
      has got trophic action on serotonergic neurons. In the present study, we provide
      evidence that serotonergic neurons express mRNA for the functional receptor of
      BDNF, trkB. Intracerebro-ventricular (i.c.v.) injection of the 5-HT-specific
      neurotoxin, 5,7-dihydroxytryptamine, which lesions serotonergic cell bodies in
      the raphe nuclei as well as their ascending projections into the dorsal
      hippocampus, caused a dramatic loss of trkB mRNA from serotonergic cell bodies of
      the dorsal raphe nucleus. In contrast, there was no change in the abundance of
      trkB mRNA within the dorsal hippocampus. These findings provide direct evidence
      for the expression of trkB mRNA by serotonergic neurons and suggest distinct
      mechanisms of action of BDNF upon serotonergic neurons at the levels of their
      cell bodies and terminal projection sites.

PMID- 11532339
TI  - Methamphetamine causes widespread apoptosis in the mouse brain: evidence from
      using an improved TUNEL histochemical method.
AB  - Terminal deoxynucleotidyl transferase (TdT)-mediated dNTP nick end labeling
      (TUNEL) histochemistry is a sensitive method to expose DNA strand breaks in
      apoptotic cells, but it is difficult to conduct on slide-mounted sections. By
      using a 80 degrees C/0.5% Triton X-100 pretreatment, we have developed a TUNEL
      histochemical approach with high specificity and sensitivity using sections from
      ischemic rat brains. Thereafter, methamphetamine (METH)-induced neuronal death
      was investigated in mice brains. The results showed that a single injection of 40
      mg/kg METH caused neuronal death in several brain areas including the striatum,
      cortex (frontal, parietal, and piriform), indusium griseum, medial habenular
      nucleus, and hippocampus. These results further confirmed the presence of METH
      induced deleterious effects in nondopaminergic neurons. The significance of these
      findings is also discussed.

PMID- 11532340
TI  - Characterisation of gene expression changes following permanent MCAO in the rat
      using subtractive hybridisation.
AB  - Failure of several putative neuroprotectants in large multicentred clinical
      trials has re-focussed attention on the predictability of pre-clinical animal
      models of stroke. Model characterisation and relationship to heterogeneous
      patient sub-groups remains of paramount importance. Information gained from
      magnetic resonance imaging (MRI) signatures indicates that the Zea Longa model of
      rat middle cerebral artery occlusion may be more representative of slowly
      evolving infarcts. Understanding the molecular changes over several hours
      following cerebral ischaemia will allow detailed characterisation of the adaptive
      response to brain injury. Using a fully characterised model of Zea Longa middle
      cerebral artery occlusion we have used the representational difference analysis
      (RDA) subtractive hybridisation method to identify transcripts that accumulate in
      the ischaemic cortex. Along with a number of established ischaemia-induced gene
      products (including MCP-1, TIMP-1, hsp 70) we were also able to identify nine
      genes which have not previously been shown to accumulate following focal
      ischaemia (including SOCS-3, GADD45gamma, Xin).

PMID- 11532341
TI  - p53 is dispensable for apoptosis but controls neurogenesis of mouse dentate gyrus
      cells following gamma-irradiation.
AB  - Mammalian cells respond to DNA insults by activating cell-cycle checkpoints. This
      may result in a temporary cell growth arrest which allows DNA repair before
      proliferation or induces apoptosis. p53 is one of the main contributors in
      regulating these activities. To get a better insight on the molecular mechanism
      underlying these activities we studied the role of p53 in apoptosis and
      neurogenesis of brain cells from adult p53(+/+) or p53(-/-) mice exposed to gamma
      irradiation. Apoptosis and neurogenesis were assessed up to 14 days following the
      injury. Five-ten hours following gamma-irradiation, cells with TUNEL positive
      nuclei were identified within the subgranular zone of dentate gyrus (DG) of both
      p53(+/+) and p53(-/-) mice. At the same time-points, pyknotic and shrinking
      nuclei were visualized by Hoechst 33258 staining. Furthermore, gamma-irradiation
      increased the number of proliferating cell nuclear antigen (PCNA) positive cells
      with a peak at 5-10 h in both animal groups. PCNA immunoreactivity was detected
      in cells exhibiting condensed nuclei as visualized by Hoechst 33258 staining.
      Neurogenesis, assessed by mitotic marker p34(cdc2) immunoreactivity, showed a
      biphasic response to gamma-irradiation both in p53(+/+) and p53(-/-) mice which
      was characterized by an early inhibition and a delayed stimulation. In p53(-/-)
      mice, the time required by DG granule cells to recover from the lesion and to
      stimulate proliferation was significantly shortened in comparison with wild-type
      mice thus resulting in an accelerated neurogenesis. Our data indicate that
      following gamma-radiation p53 plays a role in regulating cell-cycle progression
      rate but it is dispensable for promoting apoptosis of DG granule cells.

PMID- 11532343
TI  - Visual-mediated regulation of retinal CaMKII and its GluR1 substrate is age
      dependent.
AB  - Previous studies have shown that multifunctional calcium/calmodulin-dependent
      protein kinase II (CaMKII) and one of its substrates, the glutamate receptor, are
      key players in experience-driven synaptic plasticity in several areas of the
      central nervous system (CNS). To determine if CaMKII and the glutamate receptor
      are regulated by visual activity in the retina, we compared dark-reared (DR; 1
      week) rats with control rats raised in a diurnal light-dark cycle (LD), at the
      following ages: postnatal day 12 (P12d), 2-month (2m) and 6-month (6m) old. The
      mRNA levels of CaMKIIalpha and beta were determined by a competitive reverse
      transcription polymerase chain reaction (competitive RT-PCR) method. The protein
      levels of these two subunits were evaluated by immunoblots. The data show that
      the mRNAs for CaMKIIalpha and beta were increased about 8-fold and 10-fold,
      respectively, in the retinae of DR P12d rats. As for the proteins, 2- and 2.6
      fold elevations for CaMKIIalpha and beta, respectively, were evident. The GluR1
      subunit of the AMPAR (AMPAR-GluR1) was also evaluated in antibody-treated blots
      and found to be increased about 2-fold after 1 week of dark rearing in the
      retinae of P12d rats. This type of experience-driven molecular change was age
      dependent, showing less increase in 2m old rats and not present in 6m old rats.
      Returning DR 2m old rats to the LD environment for 1 week was sufficient to
      restore the dark-induced changes to the levels of the age-matched LD controls.
      Based on the data, a theoretical model for activity-dependent modulation of the
      developing retinal synapses is proposed.

PMID- 11532342
TI  - NMDA receptor antagonism modifies the synergistic regulation of striatal
      tachykinin gene expression induced by dopamine D(1) and serotonin(2) receptor
      stimulation following neonatal dopamine depletion.
AB  - Co-application of SKF-38393 (dopamine D(1) agonist; 1 mg/kg) and DOI
      (serotonin(2) agonist; 1 mg/kg) induced a synergistic increase in striatal
      preprotachykinin (PPT) mRNA levels in adult rats 60 days after neonatal
      intracerebroventricular injection of 6-hydroxydopamine. This magnitude of
      response was not observed in intact (vehicle-injected) rats and was restricted to
      the dorsomedial (DM, 333+/-25% of lesion) subregion of the anterior striatum,
      with smaller increases observed in the dorsolateral striatum (DL, 206+/-26% of
      lesion). A single i.p. injection of MK-801 (NMDA antagonist; 0.1 mg/kg)
      administered prior to dopamine D(1) (D(1)) and serotonin(2) (5-HT(2)) receptor co
      stimulation suppressed the synergistic regulation of PPT mRNA expression in the
      DM striatum, but also produced a large increase in PPT message levels within the
      DL striatum (321+/-17% of lesion). These data suggest that the synergistic
      regulation of PPT mRNA within the DM striatum induced by D(1)/5-HT(2) receptor co
      stimulation in the dopamine lesioned rat is dependent on NMDA receptor activity.
      However, MK-801 may simultaneously potentiate striatal PPT mRNA expression by a
      separate mechanism due to the changed environment of the dopamine-depleted basal
      ganglia.

PMID- 11532344
TI  - Notch receptors and hematopoiesis.
AB  - Notch receptors are involved in a variety of cell-fate decisions that affect the
      development and function of many organs, including hematopoiesis and the immune
      system. There are four mammalian Notch receptors that have only partially
      overlapping functions despite sharing similar structures and ligands. The ligands
      for Notch are transmembrane proteins expressed on adjacent cells, including
      Jagged and Delta, and it is quite possible that signaling is bidirectional. A
      large Notch precursor protein is proteolytically cleaved to form the mature cell
      surface receptor. Ligand binding induces additional proteolytic events followed
      by translocation of the intracellular domain to the nucleus. There, Notch
      interacts with transcription factors such as RBPJ kappa, activating transcription
      of basic helix-loop-helix genes such as HES1. These in turn regulate expression
      of tissue-specific transcription factors that influence lineage commitment and
      other events. In this review, the details of Notch signaling will be discussed,
      with a focus on what is known about the role of Notch in hematopoiesis.

PMID- 11532345
TI  - The effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) on
      primitive hematopoietic stem cell (PHSC) function and numbers, after
      chemotherapy.
AB  - OBJECTIVE: Primitive hematopoietic stem cell function was assessed after
      cyclophosphamide with granulocyte-macrophage colony-stimulating factor (GM-CSF),
      with or without preadministration of interleukin-1, using competitive
      repopulation. METHODS: C57B6/J mice injected with one or four biweekly
      intravenous injections of cyclophosphamide, 200 mg/kg, received granulocyte
      macrophage colony-stimulating factor, 1 microg, subcutaneously for 5 days,
      beginning 24 hours after cyclophosphamide. Alternatively, mice were injected with
      interleukin-1, 1 microg, 20 hours before administration of drug or drug and
      cytokine. Marrow obtained from mice sacrificed 4 weeks after the last dose of
      drug or drug and cytokine was used in competitive repopulation. RESULTS:
      Significant reductions in marrow repopulating ability occurred after a single
      dose of cyclophosphamide or multiple injections. Repopulating units (RU) were
      calculated, and both binomial and Poisson models for estimation of primitive
      hematopoietic stem cell (PHSC) numbers were used. RU were significantly
      diminished for all treatment groups when compared to controls. PHSC numbers were
      not significantly affected by either regimen of cyclophosphamide given alone.
      Addition of GM-CSF to cyclophosphamide, whether the latter was given in single or
      multiple doses, led to further, although insignificant, declines in repopulating
      ability, as well as PHSC and RU numbers. Interleukin-1 usage exacerbated the
      observed repopulating defect. There was evidence of replicative failure in
      individual cells, indicating a qualitative defect also. SUMMARY: Additive stem
      cell depletion and qualitative replicative defect occur after chemotherapy
      cytokine usage. However, the replicative defect of PHSC seen after addition of GM
      CSF is not significantly worse than that seen with cytotoxic drug use alone.

PMID- 11532346
TI  - Expression of multiple genes regulating cell cycle and apoptosis in
      differentiating hematopoietic cells is dependent on iron.
AB  - OBJECTIVE: Iron plays critical roles in many biological processes including
      hematopoietic cell growth and differentiation. Iron is essential for the
      differentiation of HL-60 promonocytes. HL-60 cells stimulated with phorbol
      myristate acetate (PMA) undergo G1/S phase cell-cycle arrest and differentiate to
      monocyte/macrophages. With iron deprivation, PMA-induced HL-60 cells bypass
      differentiation and undergo apoptosis. To investigate the molecular basis
      underlying this observation, we used commercially available gene microarrays to
      evaluate expression of multiple genes involved in the regulation of cell cycling
      and apoptosis. METHODS: We treated HL-60 cells with PMA +/- desferrioxamine (DF),
      a potent iron chelator, to produce iron deprivation. Cells were cultured for 48
      hours, and cDNA was prepared and radiolabeled with alpha-(32)P dCTP, then
      hybridized to gene arrays containing specific cDNA fragments. RESULTS: Expression
      of 11 of 43 genes was inhibited greater than 50% by iron deprivation. These genes
      were Rb; p21 (WAF1/CIP1); bad; cdk2; cyclins A, D3, E1; c-myc; egr-1; iNOS; and
      FasL. For each gene the microarray results were confirmed by RT-PCR and/or
      Northern or Western blotting. Nuclear transcription assays indicated that the
      role of iron in Rb expression was to support gene transcription. Addition of
      ferrioxamine (iron saturated DF) instead of DF to PMA-induced cells did not
      affect gene expression, indicating that diminished expression was due to iron
      deprivation, not nonspecific toxicity. CONCLUSION: Iron supports expression of
      multiple cell cycle-regulatory and apoptosis-related genes during HL-60 cell
      differentiation, and, in this way, is involved in regulation of a critical cell
      decision point-the decision to pursue a differentiation-related or apoptotic
      pathway.

PMID- 11532347
TI  - Absence of major histocompatibility class II expression does not impair
      hematopoiesis in mice.
AB  - OBJECTIVE: Major histocompatibility class II (MHC II) molecules are among the
      earliest antigens to be expressed in hematopoietic progenitor cells; however, the
      functional role of these molecules in hematopoiesis remains controversial. We
      examined the role of MHC II antigens during hematopoiesis using a mouse model of
      MHC II deficiency related to the absence of the critical transcriptional
      activator, CIITA. METHODS: Sca-1(-), Sca-1(+)lin(+), and Sca-1(+)lin(-)
      populations of marrow cells from CIITA(-)(/-) and wild-type mice were analyzed by
      immunofluorescence for MHC II expression. Hematopoietic capacity was assessed in
      CIITA(-/-) and wild-type mice by CFU-S, CFU-GM, and radiation sensitivity assays.
      RESULTS: Flow cytometric characteristics of hematopoietic progenitors from CIITA(
      /-) and wild-type mice were identical except for the absence of MHC II expression
      in CIITA null mice. There were no significant differences in capacity for
      hematopoietic reconstitution and clonogenicity as measured by radiation
      sensitivity, CFU-S, and CFU-GM assays among CIITA(-/-) and wild-type mice.
      CONCLUSIONS: These experiments show that downregulation of MHC II gene
      transcription does not effectively alter normal hematopoiesis, and provide strong
      evidence that MHC II expression on hematopoietic progenitors is not required for
      normal hematopoietic development.

PMID- 11532348
TI  - Expression of IL-6 and IL-6 receptors by circulating clonotypic B cells in
      multiple myeloma: potential for autocrine and paracrine networks.
AB  - OBJECTIVE: To investigate the participation of clonotypic MM B cells in the IL-6
      network in patients with multiple myeloma. METHODS: CD19(+) B cells from 45
      patients with multiple myeloma and from 18 healthy donors were sorted and their
      expression of IL-6, IL-6 receptor (CD126) characterized by flow cytometry, in
      situ RT-PCR, and ELISA measurement of IL-6 and soluble IL-6R. Expression of CD31
      was detected by flow cytometry. RESULTS: Interleukin-6 (IL-6) is a pleiotropic
      cytokine often overexpressed in multiple myeloma (MM). IL-6 induces growth and
      inhibits apoptosis of MM plasma cells, and upregulates the activity of
      osteoclasts. MM plasma cells, the most mature component of the MM clone, secrete
      IL-6 and induce IL-6 production from other cell types. However, the MM clone also
      includes circulating clonotypic B lymphocytes. Using ELISA and in situ RT-PCR we
      demonstrate here that, unlike the healthy control B cells, MM B cells express IL
      6 mRNA and secrete IL-6 protein. In vitro, MM B cells were the major producers of
      IL-6 in peripheral blood mononuclear cells. On average, 50% of MM B cells express
      the IL-6 receptor (IL-6R, CD126), suggestive of autocrine stimulation. They also
      express CD31, potentially facilitating their paracrine interactions with
      osteoclast precursors. CONCLUSION: Secretion of IL-6 by circulating clonotypic B
      cells in MM may contribute to the autocrine and paracrine cytokine networks that
      maintain the malignant clone and are responsible for disruption of normal bone
      metabolism in this incurable disease.

PMID- 11532349
TI  - Inhibition of tyrosine kinase activity induces caspase-dependent apoptosis in
      anaplastic large cell lymphoma with NPM-ALK (p80) fusion protein.
AB  - OBJECTIVE: The t(2;5)(p23;q35) translocation creates a fusion gene NPM-ALK (p80)
      that encodes a product with tyrosine kinase activity believed to play an
      important role in development of anaplastic large cell lymphoma (ALCL). Our study
      was aimed to analyze tyrosine kinase activity and phosphotyrosine in ALCLs. We
      were also interested in determining the effect of tyrosine kinase inhibitors on
      survival of ALCL. METHODS: Eleven cases of ALCL and three ALCL cell lines with
      t(2;5)(Karpas-299, SUPM2, SU-DHL-1) and 10 Hodgkin's disease (HD) samples were
      stained with anti-phosphotyrosine antibody. The tyrosine kinase activity, p80
      phosphorylation, and the apoptotic effects of two tyrosine kinase inhibitors,
      herbimycin A and STI-571, were determined on ALCL cell lines. RESULTS: Herbimycin
      A had showed both a time- and dose-dependent apoptotic effect on all three cell
      lines, while STI-571 demonstrated a minimal effect. Following herbimycin A
      treatment, a decrease in tyrosine kinase activity in the ALCL cell lines and
      inhibition in NPM-ALK (p80) autophosphorylation was demonstrated by
      immunoprecipitation and Western blotting. Herbimycin A-induced apoptosis was
      accompanied by caspase-3 activation. Furthermore, apoptosis induced by herbimycin
      A was blocked by both z-VAD-FMK and z-DEVD-FMK, suggesting a critical role of
      caspases. CONCLUSIONS: These findings indicate that tyrosine kinase activity is a
      common characteristic of ALCLs and necessary for ALCL cell survival. These
      findings further suggest that therapies targeting tyrosine kinases, including
      p80, may have clinical utility.

PMID- 11532350
TI  - Oncostatin M suppresses generation of lymphoid progenitors in fetal liver by
      inhibiting the hepatic microenvironment.
AB  - OBJECTIVE: Interaction between hematopoietic cells and stromal cells is important
      for regulation of hematopoiesis. Numerous soluble and membrane-bound factors
      directly regulating hematopoiesis have been documented, but little is known about
      how stromal cell activity is controlled. We previously reported that fetal
      hepatic cells in primary culture create the hematopoietic microenvironment and
      support expansion of blood cells from hematopoietic stem cells. In this study, we
      focused on lymphopoiesis reconstituted in our culture system and analyzed how
      stroma-mediated lymphopoiesis is regulated during embryonic development.
      MATERIALS AND METHODS: Subconfluent cultures of murine fetal hepatic cells were
      cocultured with hematopoietic stem cells derived from fetal liver in the presence
      of various cytokines. After 10 days of incubation, hematopoietic cells floating
      over the stromal layer were analyzed by various assays, including cell
      proliferation and FACS analysis. RESULTS: We found that oncostatin M, an inducer
      of hepatic development, strongly inhibited generation of B220(+) lymphocytic
      cells and colony-forming unit-interleukin-7 (CFU-IL-7) from hematopoietic stem
      cells in our coculture system. In contrast, oncostatin M did not directly inhibit
      proliferation of B cells in response to IL-7 and SCF in semisolid cultures.
      Analysis of antigen expression in lymphoid cells revealed that oncostatin M
      apparently did not arrest cells at a particular stage of B-cell development.
      CONCLUSIONS: The results suggest that oncostatin M inhibits lymphopoiesis by
      suppressing stromal activity of fetal hepatic cells to stimulate generation of
      CFU-IL-7 from their progenitors rather than by acting directly on lymphocytic
      cells.

PMID- 11532351
TI  - Transforming growth factor-beta(1) induces apoptosis in CD34(+)CD38(-/low) cells
      that express Bcl-2 at a low level.
AB  - OBJECTIVE: Transforming growth factor-beta(1) (TGF-beta(1)) strongly inhibits the
      proliferation and differentiation of primitive CD34(+)CD38(-) hematopoietic
      cells. In contrast, Flt3 ligand (FL) is a positive effector of CD34(+)CD38(-/low)
      cell proliferation. Because apoptosis plays a critical role in hematopoietic
      development, TGF-beta(1) and FL were analyzed as possible modulators of
      apoptosis. Specifically, this report examined expression of apoptotic promoters
      Bax and Bad and apoptotic inhibitors Bcl-2 and Bcl-x (all members of the Bcl-2
      protein family). Protein levels were determined in fresh and cultured
      CD34(+)CD38(+) cells and CD34(+)CD38(-/low) cells with and without treatment with
      TGF-beta(1) and FL. MATERIALS AND METHODS: Cells fractions were purified by
      sorting CD34(+)-enriched mononuclear cells from mobilized peripheral blood.
      Expression of Bcl-2, Bcl-x, Bax, and Bad and the extent of apoptosis were
      determined by flow cytometric analysis of freshly isolated cells and cells
      cultured with TGF-beta(1) and FL effectors. RESULTS: TGF-beta(1) reduced
      CD34(+)CD38(+) cell expansion and arrested cell division. Inhibition of growth
      was not accompanied by an increase in apoptosis. In CD34(+)CD38(-)(/low) cells,
      serum TGF-beta(1) and added TGF-beta(1) inhibited cell growth and significantly
      increased apoptotic cell death. Freshly isolated CD34(+)CD38(+) and CD34(+)CD38(
      /low) cells expressed Bcl-2 at similar low levels. However, after 3 days, Bcl-2
      expression was markedly higher in cultured CD34(+)CD38(+) cells. TGF-beta(1)
      significantly increased Bax expression in both fractions after 3 days cultivation
      (p = 0.0034). Thus, addition of TGF beta-1 further reduced the already low Bcl
      2:Bax ratio in CD34(+)CD38(-/low) cells. CONCLUSIONS: Compared to CD34(+)CD38(+)
      cells, CD34(+)CD38(-/low) cells were slow to up-regulate expression of Bcl-2
      during ex vivo culture. TGF-beta(1) up-regulated Bax expression by both
      CD34(+)CD38(+) and CD34(+)CD38(-)(/low) cells and promoted apoptosis in the
      latter fraction. This suggests that the preferential induction of apoptosis in
      primitive cells by TGF-beta(1) may be due to its further reduction of the Bcl
      2:Bax ratio.

PMID- 11532352
TI  - Functional heterogeneity within rhodamine123(lo) Hoechst33342(lo/sp) primitive
      hemopoietic stem cells revealed by pyronin Y.
AB  - OBJECTIVE: The aim of this study was to determine the function of primitive
      hematopoietic stem cells (PHSC) at phases G(0) and G(1) of the cell cycle.
      MATERIALS AND METHODS: A combination of supravital dyes rhodamine123 (Rh),
      Hoechst33342 (Ho), and pyronin (PY) was used to isolate the G(0) and G(1) subsets
      of PHSC. A competitive repopulation assay was used to evaluate their in vivo
      function. RESULTS: We confirmed that the Rh(lo)Lin(-)Kit(+)Sca-1(+) PHSC were
      relatively quiescent when compared with the more mature Rh(hi)Lin(-)Kit(+)Sca
      1(+) HSC and Rh(hi)Lin(-)Kit(+)Sca-1(-) progenitors. In addition, cells with
      Rh(lo)Lin(-)Kit(+)Sca-1(+), Rh(lo)Ho(lo)Lin(-)Sca-1(+), or Rh(lo)Ho(sp)Lin(-)Sca
      1(+) phenotypes identified the same cell population. We further subfractionated
      the Rh(lo)Ho(lo/sp)Lin(-)Sca-1(+) PHSC using PY into PY(lo) and PY(hi) subsets.
      Limiting dilution analysis revealed that the frequency of long-term in vivo
      competitive repopulating units (CRU) of the PY(lo)Rh(lo)Ho(lo/sp) PHSC was 1 in
      10 cells, whereas there was at least a three-fold lower frequency in those
      isolated at the G(1) phase (PY(hi)). We found a dose-dependent PY-mediated
      cytotoxicity that at moderate concentration affected most of the murine
      hematopoietic compartment but spared the early HSC compartment. CONCLUSION: Our
      data confirm that the HSC compartment is hierarchically ordered on the basis of
      quiescence and further extend this concept to PY-mediated cytotoxicity. PY
      supravital dye can be used to reveal functional heterogeneity within the
      Rh(lo)Ho(lo/sp) PHSC population but is of limited use in dissecting the
      relatively more mature hematopoietic stem/progenitor cell population.

PMID- 11532353
TI  - Administration of granulocyte colony-stimulating factor induces
      hyporesponsiveness to lipopolysaccharide and impairs antigen-presenting function
      of peripheral blood monocytes.
AB  - OBJECTIVE: The incidence and severity of acute graft-vs-host disease after
      allogeneic transplantation of granulocyte colony-stimulating factor (G-CSF)
      mobilized peripheral blood stem cells (PBSC) are not greater than those after
      conventional bone marrow transplantation despite infusion of more than one log
      greater number of donor T cells in PBSC. It has been postulated that monocytes
      from G-CSF-mobilized donors suppress alloreactivity of donor T cells. MATERIALS
      AND METHODS: We investigated the phenotype and function of monocytes in normal
      individuals receiving 10 microg/kg of G-CSF for 4 days. RESULTS: Monocytes were
      phenotypically and functionally different after G-CSF administration from steady
      state monocytes. They were characterized by an increased CD14(+)CD16(+)
      subpopulation, reduced expression of HLA-DR, and diminished ability to produce
      tumor necrosis factor-alpha and interleukin-10 to lipopolysaccharide, compared
      with steady-state monocytes. These alterations were not replicated by culturing
      monocytes with G-CSF in vitro, suggesting an indirect effect of G-CSF. In
      addition, the antigen-presenting function of G-CSF-mobilized monocytes was
      impaired. CONCLUSION: Hyporesponsiveness of G-CSF-treated monocytes to
      lipopolysaccharide with regard to tumor necrosis factor-alpha production,
      together with impaired antigen-presenting function, may be responsible for the
      unexpectedly low incidence of graft-vs-host disease after G-CSF-mobilized PBSC
      transplantation.

PMID- 11532354
TI  - HOXB4 overexpression mediates very rapid stem cell regeneration and competitive
      hematopoietic repopulation.
AB  - OBJECTIVE: Hox transcription factors have emerged as important regulators of
      hematopoiesis. In particular, we have shown that overexpression of HOXB4 in mouse
      bone marrow can greatly enhance the level of hematopoietic stem cell (HSC)
      regeneration achieved at late times (> 4 months) posttransplantation. The
      objective of this study was to resolve if HOXB4 increases the rate and/or
      duration of HSC regeneration, and also to see if this enhancement was associated
      with impaired production of end cells or would lead to competitive reconstitution
      of all compartments. METHODS: Retroviral vectors were generated with the GFP
      reporter gene +/- HOXB4 to enable the isolation and direct tracking of transduced
      cells in culture or following transplantation. Stem cell recovery was measured by
      limit dilution assay for long-term competitive repopulating cells (CRU). RESULTS:
      HOXB4-overexpressing cells have enhanced growth in vitro, as demonstrated by
      their rapid dominance in mixed cultures and their shortened population doubling
      time. Furthermore, HOXB4-transduced cells have a marked competitive repopulating
      advantage in vivo in both primitive and mature compartments. CRU recovery in
      HOXB4 recipients was extremely rapid, reaching 25% of normal by 14 days
      posttransplant or some 80-fold greater than control transplant recipients, and
      attaining normal numbers by 12 weeks. Mice transplanted with even higher numbers
      of HOXB4-transduced CRU regenerated up to but not beyond the normal CRU levels.
      CONCLUSIONS: HOXB4 is a potent enhancer of primitive hematopoietic cell growth,
      likely by increasing self-renewal probability but without impairing homeostatic
      control of HSC population size or the rate of production and maintenance of
      mature end cells.

PMID- 11532355
TI  - Safety in the globalising knowledge economy: an analysis by paradoxes.
AB  - There is a widespread recognition of a 'crisis' in official scientific expertise,
      related to the increase of 'uncertainty' and the loss of 'trust', and whose cure
      is believed to lie in 'participation'. I argue that the crisis results from
      structural features of the globalising knowledge economy, and the contradictory
      roles of governments, acting both as promoters of global business enterprise and
      also as regulators on behalf of a sophisticated and suspicious public. I explain
      the crisis by substituting 'safety' for 'risk' as the operative concept, and also
      using 'paradox' as an explanatory tool. I produce a closed-cycle paradox,
      analogous to the classic Catch-22, to exhibit the contradictions in the
      situation. I discuss ways of resolving these, which include the recognition of
      policy-critical ignorance and the adoption of the perspective of post-normal
      science.

PMID- 11532356
TI  - The risk game.
AB  - In the context of health, safety, and environmental decisions, the concept of
      risk involves value judgments that reflect much more than just the probability
      and consequences of the occurrence of an event. This article conceptualizes the
      act of defining and assessing risk as a game in which the rules must be socially
      negotiated within the context of a specific problem. This contextualist view of
      risk provides insight into why technical approaches to risk management often fail
      with problems such as those involving radiation and chemicals, where scientific
      experts and the public disagree on the nature of the risks. It also highlights
      the need for allowing the interested and affected parties to define and play the
      game, thus emphasizing the importance of institutional, procedural, and societal
      processes in risk management decisions.

PMID- 11532357
TI  - Regulating safety in an unsafe world (risk reduction for and with communities).
AB  - Safety regulators and the public they serve often have contrasting views on risk
      perception and the veracity of institutional estimates of risk and harm. Conflict
      and distrust between these groups is often a result of a lack of public
      involvement in decision making on safety related matters. Such concerns also
      emerge from differences in professional training, authority and experience
      between the groups. Fire services internationally, carryout fire safety
      assessments on behalf of communities. This assessment role is unusual in that
      unlike conventional approaches to regulatory safety assessment, fire fighters are
      direct end-users of their own regulatory assessment and closer to the people they
      protect. This paper discusses how fire services are beginning to seek closer
      links with communities by defining clear regulatory frameworks for conventional
      safety assessments and conceptual frameworks that allow a redefinition of their
      role towards establishing partnerships with communities to promote sustained
      safety.

PMID- 11532358
TI  - Risk as social process: the end of 'the age of appealing to the facts'?
AB  - This paper utilises the notion of the risk society to argue that the ways in
      which technical practices, knowledge and rationality have become structured into
      governance are counter-productive and now instrumental to the proliferation of
      risk and destabilisation of governance. This problem is epitomised by how
      decisions have evolved to become a matter determined by 'facts' rather than by a
      determination of the community impact of outcomes and further compounded by the
      institutionally embedded blindness to wider social concerns that this entails. It
      is argued that what are required are processes integrating 'factual' technical
      and 'value-laden' societal concerns and avenues for this and their ramifications
      are elaborated and explored. Central to such developments will be a
      democratisation of technical practices and the institutions in which they are
      embedded. The broader political implications of these developments are examined
      and found to involve a radical extension of democracy involving an extensive
      reshaping of the topography of governance.

PMID- 11532359
TI  - Science and precaution in the appraisal of electricity supply options.
AB  - The technological risks associated with electricity generating options are a
      crucial consideration in the governance of energy strategies. Conversely, many
      central issues in the broader social debate over the governance of environmental
      risk (such as acid gas emissions, radioactive waste management, nuclear safety
      and global climate change) relate very strongly to technology choice in the
      electricity supply sector. The particularities of this field, therefore, offer a
      topical and pertinent case with which to explore the relationship between science
      and precaution in the governance of technological risk. By reference to the
      electricity sector, the present paper examines the contrasts between 'risk-based'
      and 'precautionary' approaches to the governance of risk, paying particular
      attention to the problems of intractable uncertainties and divergent values. A
      number of theoretical and methodological issues in conventional risk-assessment
      and cost-benefit analysis are examined and their practical implications for
      appraisal explored. Attention then turns to the form that might be taken by
      approaches to the governance of energy risks that are at the same time
      scientifically well-founded and precautionary. Conclusions are drawn for decision
      and policy making in this area.

PMID- 11532360
TI  - Prospects for public participation on nuclear risks and policy options:
      innovations in governance practices for sustainable development in the European
      Union.
AB  - We outline the potential participative governance and risk management in
      application to technological choices in the nuclear sector within the European
      Union (EU). Well-conducted public participation, stakeholder consultation and
      deliberation procedures can enhance the policy process and improve the robustness
      of strategies dealing with high-stakes investment and risk management challenges.
      Key nuclear issues now confronting EU member states are: public concern with
      large-scale environmental and health issues; the Chernobyl accident (and others
      less catastrophic) whose effect has been to erode public confidence and trust in
      the nuclear sector; the maturity of the nuclear plant, hence the emerging
      prominence of waste transportation, reprocessing and disposal issues as part of
      historical liability within the EU; the nuclear energy heritage of central and
      eastern European candidate countries to EU accession. The obligatory management
      of inherited technological risks and uncertainties on large temporal and
      geographical scales, is a novel feature of technology assessment and governance.
      Progress in the nuclear sector will aid the development of methodologies for
      technological foresight and risk governance in fields other than the nuclear
      alone.

PMID- 11532361
TI  - Chains of damages and failures in a metropolitan environment: some observations
      on the Kobe earthquake in 1995.
AB  - The interaction and the couple effects that may occur as induced and indirect
      consequences of any triggering hazard in metropolitan areas is one of the most
      important problems to be tackled during disasters, as the Kobe earthquake in 1995
      showed very clearly. The analysis of direct, secondary and indirect effects of
      the Kobe earthquake suggests to substitute the concept of chain of losses and
      failures to the simple couple hazardous event-damages which is currently used.
      Not only parameters related to physical weakness or strength of the built
      environment should be considered by scientists, experts and decision-makers.
      Organisational, social, and systemic factors are equally crucial to understand
      the magnified dimension of disasters at increasing levels of exposed systems
      vulnerability. Linking failures due to different kinds of vulnerability one to
      the other permits to reconstruct complete event scenarios, where social and
      organisational elements are not simply added to the 'hard' components of cities,
      but contribute to explain why failures and losses occurred and why it took so
      long to repair them. Lifeline damage assessment provides a good example to show
      how physical, organisational and systemic vulnerabilities are intimately
      connected one to the other. The point of view from which governance problems
      related to prevention and emergency preparedness will be looked at is that of an
      urban and regional planner. When planners look for design solutions suitable for
      a specific town or region, they must constantly bridge between hard technical
      matters and social and economical concerns. Furthermore, they are forced to
      consider in their projects spatial and geographic dimensions. Those two typical
      features of planners' approach to problem solving can be interesting for scholars
      in the field of risk assessment and mitigation research.

PMID- 11532362
TI  - Increasingly intolerable boundaries: future control of environmental pollution.
AB  - In recent years, there have been a number of toxic accidents on the sea and on
      land which have caused pollution down current, down wind and down stream. Four
      were dramatic and these four have led to substantial changes in the way we deal
      with risk to the environment. There have also been increasing concerns about a
      less spectacular but equally concerning problem, acid rain, though attempts to
      deal with this problem have been less successful. Perhaps the drama was lacking.
      In all these cases, unfortunately, the less developed countries can ill afford
      the costs of prevention and this means they are often the home of environmentally
      unfriendly development. While the current approaches to such problems will
      continue, it is likely that the countries on the receiving end of such pollution,
      especially if they have economic and military power, will seek more forceful
      solutions. One outcome may be a UN-sponsored environmental police force.

PMID- 11532363
TI  - Chemical safety and governance in Brazil.
AB  - Chemical safety is recognized in Agenda 21(UNCED--Rio 92), as one of the most
      serious problems to be faced worldwide being a problem not just of governability,
      restricted more to the role of states and governments, but of governance at the
      national and international levels. It poses greater challenges for countries like
      Brazil where the issues of democracy, security, sustainability and equity, which
      are fundamental to governance, are merely incipient and still far from solved.
      Taking as references the analysis of four cases in the Brazilian context, we
      illustrate the situation from less densely populated areas (as in the cases of
      mercury use by gold miners in the Amazon and pesticides in agricultural producing
      areas), through medium-sized towns (as in the accident with cesium 137 in
      Goiania), to the major urban and industrial centers (as in the cases of lead from
      battery renovators and benzene in the oil and steel industries and oil
      refineries). What can be seen is a situation where problems connected with
      chemical safety have grown in intensity and extent far more than the capacity to
      deal with them. In industrializing countries, the formulation of chemical safety
      policies must take into account not only the complexity and uncertainties
      involved in understanding the problems, but also the aspects relating to the
      different modes and levels of vulnerability. This is necessary in order to
      attempt to build better contextualized and more participatory knowledge and
      decision-making processes at the local and global levels, which we take as basic
      prerequisites for governance.

PMID- 11532364
TI  - Mining conflicts, environmental justice, and valuation.
AB  - In this article some historical and contemporary mining conflicts are described.
      The international environmental liability of mining corporations is discussed.
      Comparisons are made with conflicts in the United States and in South Africa
      which fall under the rubric of the Environmental Justice movement. Such conflicts
      are fought out in many languages, and the economic valuation of damages is only
      one of such languages. Who has the power to impose particular languages of
      valuation? Who rules over the ways and means of simplifying complexity, deciding
      that some points of view are out of order? Who has power to determine which is
      the bottom-line in an environmental discussion?

PMID- 11532365
TI  - Incentives for mitigation investment and more effective risk management: the need
      for public-private partnerships.
AB  - A key question facing both well-developed industrial countries and emerging
      economies is how to reduce future disaster losses while still providing financial
      protection to victims from these events. This paper proposes a strategy for the
      use of cost-effective risk mitigation measures coupled with insurance and/or new
      capital market instruments to achieve these objectives. The mix of these measures
      will depend on the governance structure and the institutional arrangements in the
      particular country. There will always be a need for a combination of policy tools
      and the interaction among key interested parties from both the private and public
      sectors in developing a disaster management strategy. Two examples, one from US
      and the other from Honduras, illustrate differences between strategies that
      countries can adopt.

PMID- 11532366
TI  - The role of risk assessments in the governance of genetically modified organisms
      in agriculture.
AB  - Controversy abounds in the governance of genetically modified organisms (GMOs)
      for use in agriculture, partly due to ideological differences. Technological
      optimism and the "shallow" and the "deep" ecology movements are three influential
      ideologies that are seen to differ both on value commitments and factual beliefs
      with respect to GMOs. Factual matters are clarified but not resolved by science,
      since the scientific community faces uncertainty and apparent contradiction
      between different research perspectives, notably molecular biology, ecology and
      the social sciences. Scientific advice plays a key role in the governance of GMOs
      and ought to be construed so as not to exclude legitimate arguments from
      ideological perspectives present in the process of governance. This paper
      analyses the role and use of risk assessments and argues that they be replaced by
      forms of advice that consider a broader spectrum of scientific evidence and
      insights, e.g. impact assessments and evaluations of inherent sources of
      uncertainty and ignorance. A few practical measures to that effect are discussed.

PMID- 11532367
TI  - Democracy and the governance of uncertainty. The case of agricultural gene
      technologies.
AB  - The use of genetically modified organisms (GMOs) in agriculture and food
      production is the object of an intense and divisive debate. Drawing on a study on
      the public perception of agricultural gene technologies carried out in five
      European countries, the article deals with the policy aspects of the issue, and
      more precisely on the relation between institutions, experts and the public in a
      context of deep uncertainty. A theoretical framework is developed and compared
      with the study findings, suggesting that issues like the GMOs one represent a
      strong case for a more participatory policy-making. My conclusions suggest a
      style of governance based on the principles of deliberative democracy, as a
      suitable approach to the confrontation of different viewpoints and forms of
      knowledge. This appears to be the best way to improve the overall quality of
      policy-making: in this I include its legitimacy, the degree of public trust, and
      also the actual quality of its products. Strengthening the role of the public
      sphere seems more effective than simply increasing direct decision-making by the
      populace, and it offers an alternative to the 'elitist' solutions to the crisis
      of representative democracy.

PMID- 11532368
TI  - From irreversibility to participation: towards a participatory foresight for the
      governance of collective environmental risks.
AB  - This paper presents a reflection on the introduction of methods and tools of
      "participative foresight" for scientific and technology policy as well as
      environmental policy fields. Future studies have recently made a comeback under
      the label of foresight. Future technology studies no longer claim to forecast the
      future, but are presented as a strategic tool for improving interaction between
      key actors and for anticipatory policy making. They can be defined as a "process
      by which one comes to a fuller understanding of the forces shaping the long term
      future which should be taken into account in policy formulation, planning and
      decision-making" [Foresight in Federal Government Policymaking, Futures Res.
      Quart. (1985) 29]. We discuss applications of this approach for perspectives on
      environmental policy and sustainable development. Foresight opens up the
      possibility of negotiating a new and more fruitful relationship or 'social
      contract' between science and technology, on the one hand, and society on the
      other. The focus has moved from merely scientific and industrial insights to
      social demand, thus emphasizing the importance of both the production and
      "supply" of innovation, and the "demand" as signaled in the views of citizens.

PMID- 11532369
TI  - Present challenges to risk governance.
AB  - The purpose of this short paper is to present the main challenges to risk
      governance in the today democratic context. The first part describes briefly the
      main characteristics of the approach to collective decision-making grounded on
      the scientific rationality, dominant in Europe for about two centuries. The
      second part describes the current difficulties encountered by the traditional
      decision-making processes when confronted with complex situations in area such as
      risk management but also in the management of other collective issues such as
      unemployment or urban violence. This description is notably based on the
      conclusions of the TRUSTNET European concerted action on risk governance issued
      in 2000. From the interdisciplinary analysis of some 11 detailed case studies of
      diversified risk governance contexts, the concerted action conclusions propose a
      model of the existing patterns of risk governance. The emergence of new co
      operative processes of decision-making (Mutual Trust Paradigm) is reported in
      contexts where the traditional approach of collective decision-making are meeting
      difficulties. The third part of the paper describes the profound changes required
      by the adoption of co-operative decision-making processes and the main conditions
      for their development in the future.

PMID- 11532370
TI  - There is no influence of a temperature rise on in vivo adsorption of UV filters
      into the stratum corneum.
AB  - Temperature influences the stratum corneum adsorption of several topically
      applied compounds. This study was designed to evaluate the influence of the
      temperature on the stratum corneum adsorption of 3 UV filters. The UV filters
      were solubilized in two vehicles, an emulsion gel and petroleum jelly and applied
      at respectively, 31 and 40 degrees C during 30 min. In vivo stratum corneum UV
      filter content was measured using the tape stripping method. Similar amounts of
      UV filter were detected in the stratum corneum when comparing applications at the
      different temperatures. Application of the UV filters in the emulsion gel
      resulted in higher stratum corneum UV filter concentrations compared with
      application in the petroleum jelly. The application temperature did not influence
      the stratum corneum adsorption of the tested UV filters while the nature of the
      vehicle significantly influenced the amount of UV filters recovered from the
      stratum corneum.

PMID- 11532371
TI  - CUSP/p63 expression in rat and human tissues.
AB  - The human homolog of KET, p63, bears strong homology to the tumor suppressor p53
      and plays an essential role in epithelial development. CUSP, the most abundant
      cutaneous product of p63, has been identified as an autoantigen in chronic
      ulcerative stomatitis (CUS). The original report of KET expression at least
      partially contradicts p63 expression subsequently reported by many different
      groups. We have examined p63 expression by Northern analysis of RNA from multiple
      human tissues and by indirect immunofluorescence of rat tissue with CUS patient
      sera. Northern analysis reveals p63 RNA in skin, thymus, placenta, skeletal
      muscle, kidney, and lung, with non-transactivating p63 RNA in skin, thymus, and
      placenta. Reverse transcriptase polymerase chain reaction (rtPCR) assays show
      abundant non-transactivating p63 RNA, and little to no transactivating p63 RNA,
      in human basal cell carcinoma as well as in normal skin adjacent to the tumors.
      p63 RNA expression was not detected in brain, heart, colon, spleen, liver, or
      small intestine. Immunofluorescence reveals p63 expression in skin, oral
      epithelium, tongue, kidney, and trachea, but not in liver, large intestine,
      testis, skeletal muscle, or heart. Focal p63 expression within tissues, the
      complex array of isoforms encoded by the gene, and the specificity of the probes
      and antibodies utilized, may all contribute to contradictory accounts of CUSP/p63
      expression.

PMID- 11532372
TI  - Evaluation of recombinant interleukin-2 immunotherapy for human hemangiosarcoma
      in a SCID mice model (WB-SCID).
AB  - We treated the patients with cutaneous hemangiosarcoma with recombinant
      interleukin-2 (rIL-2) immunotherapy that showed clear therapeutic effects. This
      immunotherapy is popular for the treatment of hemangiosarcoma in Japan. The
      purpose of this study is to clarify the clinical effects in an animal experiment.
      After establishing a SCID mouse model of human hemangiosarcoma WB-SCID, we used
      this model to investigate anti-tumor effects of rIL-2 and LAK cells. We
      demonstrated that hemangiosarcoma cells are LAK-sensitive, and LAK cells induced
      by rIL-2 suppress the growth of hemangiosarcoma. Our results may assure the
      clinical effects of rIL-2 immunotherapy on hemangiosarcoma.

PMID- 11532373
TI  - Deficiency of the decorin core protein in the variant form of Ehlers-Danlos
      syndrome with chronic skin ulcer.
AB  - Decorin belongs to a family of small leucine-rich dermatan sulfate proteoglycans
      that are involved in the control of matrix organization and cell growth. Here, we
      described a patient whose skin glycosaminoglycans showed extremely decreased
      amount of dermatan sulfate compared with a normal control skin. This patient
      presented clinical features of Ehlers-Danlos syndrome with a chronic skin ulcer.
      Western blotting revealed that the deficiency of dermatan sulfate was due to the
      defect of decorin core protein. Beta-xyloside, an initiator of dermatan sulfate
      glycosaminoglycan chain elongation, enhanced the synthesis of dermatan sulfate in
      the fibroblasts of the patient to a similar extent to that of control. This
      result indicated that the enzymes for the elogation of dermatan sulfate side
      chains were normal. Northern blotting demonstrated remarkable reduction of
      decorin mRNA level, while biglycan mRNA level was concomitantly increased and
      procollagen alpha1(I) mRNA level was normal. cDNA and exons sequencing analysis
      showed there was no mutation in decorin gene of the patient. IL-1beta stimulated
      decorin expression to about 140% in control fibroblasts while about 110% in
      patient fibroblasts. On the other hand, TGF-beta1 resulted in 40% reductions of
      decorin expression in both control and patient fibroblasts. These data suggested
      that reduced decorin expression of fibroblasts from the patient of Ehlers-Danlos
      syndrome may be due to abnormalities in the regulatory regions, which is
      responsible for the IL-1beta stimulation.

PMID- 11532374
TI  - Effects of collagen matrix containing transforming growth factor (TGF)-beta(1) on
      wound contraction.
AB  - We evaluated the effectiveness of transforming growth factor (TGF)-beta(1) on
      wound contraction, both alone and in combination with collagen matrix, using an
      in vivo delayed wound healing type model. To clarify the mechanisms involved in
      the effectiveness of TGF-beta(1), we also used a fibroblast-populated collagen
      gel contraction in vitro model. Although we found that TGF-beta(1) significantly
      accelerated contraction of the fibroblast-populated collagen gel in vitro, we
      demonstrated that both collagen matrix alone and 1.0 microg of TGF-beta(1) alone
      significantly inhibited wound contraction in the in vivo model. In addition, the
      combination of TGF-beta(1) and collagen matrix was much more effective than TGF
      beta(1) alone, a finding which was supported by histopathological examination.
      Wounds treated with collagen matrix containing TGF-beta(1) showed horizontal
      rearrangement of collagen fibers in the dermal part as well as evidence of active
      fibroblast proliferation, which was not observed in the scar regions of controls.
      These results show that the application of TGF-beta(1) treated collagen matrix is
      effective for preventing contraction producing so called "neodermis" in treating
      a delayed healing type model and may be highly beneficial for treating chronic
      wounds.

PMID- 11532375
TI  - In vitro and in vivo expression of protoporphyrin IX induced by lipophilic 5
      aminolevulinic acid derivatives.
AB  - We estimated the expression level of protoporphyrin IX (PpIX) induced by
      lipophilic 5-aminolevulinic acid (ALA) derivatives and observed its histological
      distribution by fluorescence microscopy. In vitro PpIX expression in Hepe2 cells
      was the highest when induced by ALA pentyl ester. This level was 2.8-fold higher
      than that induced by ALA after 4 h incubation and 2.5-fold higher than that after
      24 h incubation. The differences between ALA pentyl ester and ALA were
      significant at both time points (P<0.01). In HeLa cells, ALA butyl ester showed
      the highest induction of PpIX, which was 2.6-fold higher than ALA after 4 h
      incubation and 3.5-fold higher after 24 h incubation. The differences were
      significant at both time points (P<0.01). In mice with squamous cell carcinoma,
      the in vivo expression of PpIX in the tumors was highest with ALA methyl ester,
      which was 1.3-fold higher than ALA. The difference was significant (P<0.01). The
      expression of PpIX by means of fluorescence microscopy was highest by ALA methyl
      ester. Under in vitro conditions, PpIX expression was efficiently induced by long
      chain ALA esters, while better in vivo PpIX induction was obtained with short
      chain ALA esters. In this study, ALA methyl ester was found to be the best among
      the ALA derivatives in inducing PpIX expression in vivo, and would be more
      effective in treatment of skin cancers than ALA.

PMID- 11532376
TI  - Expression profiling of cancer-related genes in human keratinocytes following non
      lethal ultraviolet B irradiation.
AB  - Ultraviolet B irradiation initiates and promotes skin cancers, photo-aging, and
      immune suppression. In order to elucidate the effect of these processes at the
      level of gene expression, we used cDNA microarray technology to examine the
      effect of ultraviolet B irradiation on 588 cancer-related genes in human
      keratinocytes at 1, 6, and 24 h post-irradiation with a mildly cytotoxic dose of
      ultraviolet B (170 mJ/cm(2)). The viability of the irradiated keratinocytes was
      75% at 24 h post-irradiation. Various cytokeratins and transcription factors were
      up-regulated within 1 h post-irradiation. After 6 h, expression of a variety of
      genes related to growth regulation (e.g. p21(WAF1), notch 4, and smoothened),
      apoptosis (e.g. caspase 10, hTRIP, and CRAF1), DNA repair (ERCC1, XRCC1),
      cytokines (e.g. IL-6, IL-13, TGF-beta, and endothelin 2), and cell adhesion (e.g.
      RhoE, and RhoGDI) were altered in human keratinocytes. These data suggest the
      changes in a cascade of gene expression in human keratinocytes occurring within
      24 h after UVB exposure. Although the roles of these cellular genes after UVB
      irradiation remain to be elucidated, microarray analysis may provide a new view
      of gene expression in epidermal keratinocytes following UVB exposure.

PMID- 11532377
TI  - Differentiated keratinocytes are responsible for TNF-alpha regulated production
      of macrophage inflammatory protein 3alpha/CCL20, a potent chemokine for
      Langerhans cells.
AB  - The recruitment of immature dendritic cells into the epidermis is a key step in
      the development of cutaneous immunity, although the mechanism remains to be
      clarified. Recently, it was reported that both macrophage inflammatory protein
      3alpha (MIP-3alpha)/CCL20 produced by keratinocytes and TNF-alpha are important
      in recruiting Langerhans cells (LC) to the epidermis. In this study, we examined
      the production of MIP-3alpha by human keratinocytes stimulated with TNF-alpha.
      Cultured keratinocytes showed enhanced expression of MIP-3alpha mRNA and protein
      when stimulated with TNF-alpha. In addition, conditioned medium from TNF-alpha
      stimulated keratinocyte cultures induced the migration of L1.2 cells expressing
      CCR6. We next examined the production of MIP-3alpha in stratified keratinocytes
      and found that, in contrast to non-stratified keratinocytes, stimulation with TNF
      alpha increased the expression of MIP-3alpha mRNA and protein. Moreover, skin
      samples grown in organ culture and treated with TNF-alpha showed MIP-3alpha in
      the keratinocytes of the spinous layer, but not in the basal layer, by
      immunofluorescence staining. Based on these results, we postulate that MIP-3alpha
      produced by keratinocytes in the spinous layer in response to TNF-alpha
      stimulation is a key chemokine responsible for the epidermal recruitment of
      Langerhans cells.

PMID- 11532378
TI  - Serum levels of interleukin-6 and interleukin-10 correlate with total skin
      thickness score in patients with systemic sclerosis.
AB  - Various growth factors and cytokines have been suggested to play a central role
      in initiating and developing fibrosis in systemic sclerosis (SSc). To determine
      which serum levels of soluble mediators are the most relevant to the degree of
      skin sclerosis in SSc, serum levels of various soluble mediators were examined by
      ELISA and correlated with skin thickening that was measured using modified Rodnan
      total skin thickness scoring (TSS) system. Serum levels of IL-4, IL-12, IL-13,
      tumor necrosis factor-alpha, connective tissue growth factor (CTGF), vascular
      endothelial growth factor, monocyte chemotactic protein-1, macrophage
      inflammatory protein-1beta, soluble IL-6 receptor, and soluble L-selectin were
      higher in SSc patients than normal controls. Levels of IL-6, IL-10, and CTGF in
      patients with diffuse cutaneous SSc were higher than patients with limited
      cutaneous SSc and controls. Serum levels of IL-6 and IL-10 positively correlated
      with TSS in patients with SSc (r=0.625, P<0.0001 and r=0.663, P<0.0001,
      respectively). In addition, IL-10 levels significantly correlated with pulmonary
      fibrosis. Thus, serum levels of IL-6 and IL-10 most strongly reflect the extent
      of skin thickening in SSc, suggesting that levels of IL-6 and IL-10 are useful
      serological indicators for skin fibrosis in SSc.

PMID- 11532379
TI  - Potential anti-androgenic activity of roxithromycin in skin.
AB  - Since acne formation is a multistep process accelerated by androgens, we examined
      whether a new anti-acne antibiotic roxithromycin (RXM) may act as anti-androgen
      using transient transfection assays in human skin fibroblasts. The result showed
      no significant effect of 0.5, 1 and 5 microg/ml RXM on 10(-9) M R1881-induced
      androgen receptor (AR) transcriptional activity. While the cotransfection of
      exogenous ARA55, a novel AR coactivator, increased AR transactivation up to 2.59
      fold, this increase was attenuated by 5 microg/ml RXM to 64.7%. Semiquantitative
      RT-PCR results showed that 0.1 mM H(2)O(2) treatment increased ARA55 mRNA
      expression level, indicating that reactive oxygen species increase the expression
      of ARA55 in skin. These results suggest that RXM may serve as anti-androgen only
      in the hypersensitive state to androgen, but not in the physiological state,
      through modulating end-organ hypersensitive condition to androgen possibly
      involving the pathway from reactive oxygen species to ARA55.

PMID- 11532380
TI  - Neurotransmitters, temperament and social functioning.
AB  - Dimensional models can be usefully employed to describe both normal and
      disordered personality. Studies in molecular genetics, receptor binding,
      peripheral monoamines and pharmacological challenges have investigated the
      neurochemical basis of personality. Substantial evidence now exists to support a
      psychobiological model but the specificity of Cloninger's theory has not always
      been confirmed. Clinical studies have shown both temperament and character
      dimensions to improve with pharmacological treatment especially in treatment
      responders. Some personality changes are found to be independent of clinical
      effects and even to occur in normal subjects. Models of personality can help in
      predicting treatment outcome but individual dimensions may not be useful. It is
      hypothesised that social adaptation is related to the character dimensions and
      different sources of evidence link these to serotonergic actions. However, recent
      clinical studies have shown a specific effect of noradrenaline on self-perception
      and social motivation. Drugs with specific actions on different neurotransmitters
      may exert a distinctive pattern of effects on personality and social behaviour.

PMID- 11532381
TI  - Review of pharmacokinetic and pharmacodynamic interaction studies with
      citalopram.
AB  - Citalopram is a selective serotonin reuptake inhibitor that is N-demethylated to
      N-desmethylcitalopram partially by CYP2C19 and partially by CYP3A4 and N
      desmethylcitalopram is further N-demethylated by CYP2D6 to the likewise inactive
      metabolite di-desmethylcitalopram. The two metabolites are not active. The fact
      that citalopram is metabolised by more than one CYP means that inhibition of its
      biotransformation by other drugs is less likely. Besides citalopram has a wide
      margin of safety, so even if there was a considerable change in serum
      concentration then this would most likely not be of clinical importance. In vitro
      citalopram does not inhibit CYP or does so only very moderately. A number of
      studies in healthy subjects and patients have confirmed, that this also holds
      true in vivo. Thus no change in pharmacokinetics or only very small changes were
      observed when citalopram was given with CYP1A2 substrates (clozapine and
      therophylline), CYP2C9 (warfarin), CYP2C19 (imipramine and mephenytoin), CYP2D6
      (sparteine, imipramine and amitriptyline) and CYP3A4 (carbamazepine and
      triazolam). At the pharmacodynamic level there have been a few documented cases
      of serotonin syndrome with citalopram and moclobemide and buspirone. It is
      concluded that citalopram is neither the source nor the cause of clinically
      important drug-drug interactions.

PMID- 11532382
TI  - Abnormal thermoregulation in drug-free male schizophrenia patients.
AB  - Schizophrenia patients may develop various thermoregulatory disturbances. We
      hypothesized that a standardized exercise-heat tolerance test [two 50-min bouts
      of walking a motor-driven treadmill at 40 degrees C (relative humidity=40%)]
      would reveal abnormal thermoregulation in drug-free schizophrenia patients. Six
      drug-free schizophrenia outpatients and seven healthy comparison subjects
      participated in this study. The schizophrenia patients exhibited significantly
      higher baseline and exertion-related rectal temperature. The relevance of these
      findings to the pathophysiology of schizophrenia-related thermoregulatory
      disorders is as yet unclear.

PMID- 11532383
TI  - Effects of the atypical antipsychotic risperidone on hostility and aggression in
      schizophrenia: a meta-analysis of controlled trials.
AB  - Atypical antipsychotics have been hypothesized to be more effective than
      classical antipsychotics in the treatment of hostility and aggression, due to
      their characteristic pharmacological profile, involving serotonergic as well as
      dopaminergic systems. In the present quantitative review the published evidence
      regarding the effects of risperidone on hostility and aggression in schizophrenia
      is evaluated. Meta-analysis of seven controlled trials revealed significant
      differences between risperidone and classical antipsychotics and between
      risperidone and placebo, although the effect size was small. Additional analyses
      in which only methodological rigorous studies were included showed highly
      significant differences (risperidone versus classical antipsychotics) and the
      effect size approached the 'medium' range. We conclude that risperidone is
      superior to classical antipsychotics and placebo in the treatment of hostility
      and aggression in schizophrenia. Neuropharmacological mechanisms that might
      account for this effect are discussed, and directions for future research are
      outlined.

PMID- 11532384
TI  - Omega-3 fatty acids as a psychotherapeutic agent for a pregnant schizophrenic
      patient.
AB  - Because of the potential adverse events and teratogenesis of antipsychotic drugs,
      it is important to find a safe and effective treatment for pregnant women with
      severe mental illness. The membrane hypothesis of schizophrenia provides a
      rationale to treat symptoms of schizophrenia with omega-3 PUFAs. We report a 30
      year-old married woman with chronic schizophrenia, who experienced an episode of
      acute exacerbation of psychotic symptoms during pregnancy. After entering into an
      open trial of omega-3 PUFAs monotherapy, she showed a dramatic improvement in
      both positive and negative symptoms of schizophrenia and a significant increase
      of omega-3 PUFA composition in erythrocyte membrane. There were no adverse
      effects in this treatment. Thus, omega-3 PUFAs could be both beneficial and
      therapeutic to pregnant schizophrenic women.

PMID- 11532385
TI  - Effects of the selective activation of 5-HT3 receptors on sleep: a
      polysomnographic study in healthy volunteers.
AB  - The respective role of various classes of central serotonin (5-HT) receptors in
      the regulation of sleep-wakefulness cycles has been the subject of many studies.
      Notably, it has been reported that 5-HT1A/B receptors are involved in the
      regulation of rapid eye movement sleep (REMS) and that 5-HT2A/C receptors
      participate in the control of slow wave sleep (SWS), but the role of 5-HT3
      receptors is less well characterised. In this study we investigated the effects
      of SR 57227A, a potent and selective 5-HT3 agonist, on the sleep EEG of normal
      young male volunteers. SR 57227A (2.5, 5, 10, 20, 40 mg o.d. and 20 mg b.i.d.) or
      placebo were administered during 7 consecutive days in seven groups of ten
      subjects using a parallel group design. Sleep EEG recordings were performed on
      days 6 and 7 after an habituation session. SR 57227A produced a dose-dependent
      shift of REMS toward the end of the night without changing REMS and SWS duration
      nor altering sleep continuity. It suggests a role for the 5-HT3 receptor in the
      human sleep-wakefulness cycle and particularly in REMS regulation.

PMID- 11532386
TI  - Panic disorder: the place of benzodiazepines and selective serotonin reuptake
      inhibitors.
AB  - This article reviews the efficacy of the benzodiazepines and the selective
      serotonin reuptake inhibitor class of antidepressant in the treatment of panic
      disorder. The benzodiazepine alprazolam has been used successfully in the
      treatment of panic disorder, but its long-term use presents problems with
      dependence. Since panic may be mediated by a dysfunction of serotonin neuronal
      pathways, there is a rationale for treatment with antidepressants that modulate
      serotonergic systems. In clinical trials, members of the SSRI class of
      antidepressant reduced panic attack frequency to zero in 36-86% of patients and
      were well tolerated over long-term administration, all important factors in
      ensuring patient compliance. In addition, antidepressants are preferable to
      benzodiazepines in the treatment of panic and comorbid depression, of which there
      is a high prevalence among panic disorder patients. This review emphasises the
      need for long-term treatment of this chronic and disabling condition with a
      therapy that is well tolerated and provides complete and sustained recovery from
      panic attacks, and resolution of anticipatory anxiety.

PMID- 11532387
TI  - Withdrawal-emergent rabbit syndrome during dose reduction of risperidone.
AB  - Rabbit syndrome (RS) is a rare extrapyramidal side effect caused by prolonged
      neuroleptic medication. Here we present a case of withdrawal-emergent RS, which
      is the first of its kind to be reported. The patient developed RS during dose
      reduction of risperidone. The symptom was treated successfully with
      trihexyphenidyl anticholinergic therapy. The underlying mechanism of withdrawal
      emergent RS in the present case may have been related to the pharmacological
      profile of risperidone, a serotonin-dopamine antagonist, suggesting the
      pathophysiologic influence of the serotonin system in the development of RS.

PMID- 11532390
TI  - Control of muscle development by dueling HATs and HDACs.
AB  - Skeletal muscle cells have provided an especially auspicious system in which to
      dissect the roles of chromatin structure in the control of cell growth,
      differentiation, and development. The MyoD and MEF2 families of transcription
      factors act cooperatively to regulate the expression of skeletal muscle-specific
      genes. Recent studies have shown that these two classes of transcription factors
      associate with histone acetyltransferases and histone deacetylases to control the
      activation and repression, respectively, of the muscle differentiation program.
      Signaling systems that regulate the growth and differentiation of muscle cells
      act, at least in part, by regulating the intracellular localization and
      associations of these chromatin remodeling enzymes with myogenic transcription
      factors. We describe the molecules and mechanisms involved in chromatin
      remodeling during skeletal muscle development.

PMID- 11532391
TI  - NFAT signaling in vertebrate development.
AB  - NFATc proteins transduce Ca(2+) signals to the nucleus and then pair with other
      proteins on DNA to generate NFAT complexes that activate transcription in
      response to both electrical and tyrosine kinase signaling. The four NFATc genes
      arose at the origin of vertebrates, implying that they have evolved for the
      development of vertebrate-specific functions, such as a complex nervous system, a
      recombinational immune system, and a vascular system with a complex heart. These
      speculations are borne out by studies of mice with null mutations in the
      different family members.

PMID- 11532392
TI  - Hematopoietic development: a balancing act.
AB  - Over the past year, significant new insights have been gained in our
      understanding of the lineage determination of red blood cells. In particular,
      evidence has emerged demonstrating that cross-antagonism of lineage-specific
      transcription factors plays an important role in determining cell phenotype by
      actively repressing alternate lineage gene programs.

PMID- 11532393
TI  - Lymphocyte development from hematopoietic stem cells.
AB  - The recent application of new techniques, such as multi-color cell sorting and
      the production of transgenic and gene-knockout mice, has contributed to a better
      understanding of lymphocyte development from hematopoietic stem cells. Now that
      we can purify progenitors at different maturational stages during lymphocyte
      development, the challenge is to understand the processes that govern each
      developmental stage transition.

PMID- 11532394
TI  - Genetic control of skeletal development.
AB  - The skeleton is a single organ composed of >200 different elements spread
      throughout the body. These skeletal elements comprise two tissues: cartilage and
      bone. Both tissues contain specific cell type(s): chondrocytes in cartilage and
      osteoblasts and osteoclasts in bone. We are beginning to understand the genetic
      control of the differentiation and function of these cells through recent
      developments in mouse and human genetics, and also through the use of molecular
      biological and biochemical techniques. The most recent advances in terms of cell
      differentiation in the skeleton are presented in this review.

PMID- 11532395
TI  - TGF-beta signalling pathways in early Xenopus development.
AB  - Many different ligands of the TGF-beta superfamily signal in the early Xenopus
      embryo and are required for the specification and patterning of the three germ
      layers as well as for gastrulation. Recent advances in the field are helping us
      understand how ligand activity is regulated both spatially and temporally, the
      mechanism by which the signals are transduced to the nucleus and how essentially
      the same signalling pathway can activate completely different sets of genes in
      different regions of the embryo.

PMID- 11532396
TI  - Monstrous attempts at adnexogenesis: regulating hair follicle progenitors through
      Sonic hedgehog signaling.
AB  - Epithelial organs such as the vertebrate hair control periodic self-renewal by
      regulating the growth of progenitor cells. Recent studies implicate Sonic
      hedgehog target gene induction in the growth of multipotent hair follicle
      epithelium and the development of a variety of hair follicle tumors such as basal
      cell carcinomas. These studies suggest Sonic hedgehog signaling may regulate
      progenitor cells in other organs.

PMID- 11532397
TI  - New aspects of Wnt signaling pathways in higher vertebrates.
AB  - The development of tissues and organs in embryos is controlled by an interplay of
      several signaling pathways that cross-talk to provide positional information and
      induce cell fate specification. One of the major signaling systems is the Wnt
      pathway which was recently shown to split into several intracellular branches
      which regulate multiple cellular functions. In the present review, we discuss
      novel members and their role in the diversification of the Wnt pathway. Many of
      these components were studied in model organisms such as C.elegans, Drosophila
      and Xenopus. Here we focus on recent studies of mutant phenotypes in Mouse and
      Zebrafish which implicate members of the Wnt pathway in processes such as axis
      and mesoderm formation, initiation of organ development and stem cell
      differentiation.

PMID- 11532399
TI  - Formation of Peyer's patches.
AB  - Formation of Peyer's patches requires complex interactions between the gut
      epithelium, the mesenchyme, and bone-marrow-derived hematopoietic progenitors.
      The first Peyer's patches anlage appear around embryonic day 15.5, when the
      endoderm has undergone transition to a simple epithelium, the lymphatic vessels
      have reached the intestinal mucosa, and mesenchymal cells have started to form
      clusters. Recent data using knockout mice provide insight into the molecular
      nature of the signals that mediate Peyer's patch ontogeny. These include members
      of the tumor-necrosis factor family and homeostatic chemokines.

PMID- 11532398
TI  - Notch signaling in lymphocyte development.
AB  - Signaling through Notch has been implicated in many cell-fate decisions during
      lymphocyte development. Recent studies have provided new clues--and raised new
      controversies--regarding the exact role that Notch signaling plays in the
      commitment of cells to the T-cell lineage. Progress has also been made in
      deducing the transcriptional program induced by Notch and the mechanism of
      oncogenic transformation by Notch in lymphocytes.

PMID- 11532400
TI  - Hepatocyte differentiation: from the endoderm and beyond.
AB  - Hepatocytes differentiate from the endoderm during embryonic development. Recent
      studies show, however, that hepatocytes can also be derived from rare cells that
      reside in the pancreas, bone marrow, and brain. Indeed, the latest discoveries
      indicate that embryonic hepatocytes normally arise by diversion of an endodermal
      cell population that would otherwise default to a pancreatic fate. Convergent FGF
      and BMP signals from distinct mesodermal cell types control this transition.
      Molecular signals that govern the differentiation of hepatocytes from non
      endodermal cells and the role of such cells in normal liver physiology remain to
      be discovered.

PMID- 11532401
TI  - Differentiation potential of adult stem cells.
AB  - In many different adult tissues, stem cells generate new cells either
      continuously or in response to injury. Such cells were thought to be limited to
      generating the types of cells normally present in the tissue where the stem cell
      resides. However, several different stem-cell populations in the adult have been
      found recently to be capable of generating additional cell types under certain
      conditions.

PMID- 11532402
TI  - Transdifferentiation and metaplasia--switching cell types.
AB  - States of developmental commitment are encoded as combinations of transcription
      factors and changes in their expression can bring about transdifferentiation or
      metaplasia. For example, ectopic expressions of Vestigial can convert Drosophila
      leg to wing; of C/EBPbeta can convert pancreatic exocrine cells to hepatocytes;
      and expression of C/EBPalpha and PPARgamma can convert myoblasts to adipocytes.

PMID- 11532403
TI  - Mouse ES cells: experimental exploitation of pluripotent differentiation
      potential.
AB  - Pluripotent ES cells can be used to generate a wide variety of cell populations
      in vitro in a manner resembling embryonic development. Recent advances in
      controlling ES cell differentiation, combined with the power of genetic and
      biochemical manipulation, are providing insights into cell biology and the
      determination of cell fate.

PMID- 11532404
TI  - Human pluripotent stem cells: a progress report.
AB  - The derivation of diploid human pluripotent stem cell lines from either human
      blastocysts or embryonic gonads in 1998 attracted a great deal of interest
      because of the widespread potential applications of these cells in research and
      in regenerative medicine. Since the initial reports, there has been some progress
      in the characterisation of blastocyst-derived stem cells, and some technical
      advances in their manipulation. Conditions for differentiation in vitro of
      pluripotent stem cells from either blastocysts or gonads have been defined. In
      some studies, committed progenitor cell populations have been isolated from mixed
      cultures of differentiating ES cells.

PMID- 11532405
TI  - The significance of malignancies incidental to microcalcifications in breast spot
      localization biopsy specimens.
AB  - BACKGROUND: Incidental breast cancer is occasionally found in spot localization
      biopsy specimens adjacent to mirocalcifications in benign breast disease. Because
      this phenomenon could prove problematic for percutaneous sampling of
      microcalcifications without excisional biopsy, we studied surgical specimens from
      patients with cancers incidental to microcalcifications and compared them with
      specimens with microcalcifications within the malignancy. METHODS: The pathology
      database at the Mount Sinai Medical Center from January 1993 to July 1998 was
      reviewed to identify breast cancer patients who underwent spot localization
      biopsy for microcalcifications. Patients presenting with microcalcifications
      within malignancy (determinate) were compared with patients with
      mirocalcifications in benign breast tissue adjacent to malignancy (incidental).
      RESULTS: Thirty-two (13%) of the 241 specimens had microcalcifications in benign
      tissue adjacent to malignancy and 209 (87%) had microcalcifications within the
      malignancy. Fifty-six percent of the incidental cases and 65% of the controls had
      ductal carcinoma in situ. Infiltrating lobular carcinoma accounted for 25% of the
      incidental cancers and 2% of the determinate cancers (P <0.001). Fifty-seven
      percent of the infiltrating carcinomas incidental to mammographic findings were
      infiltrating lobular carcinoma compared with 7% of the nonincidental infiltrating
      carcinomas. None of the incidental invasive carcinomas were poorly differentiated
      (P = 0.002). There were no significant differences with regard to age, tumor
      size, stage, differentiation, estrogen and progesterone receptors, type of
      surgery and final margin status. In none of the patients with incidental
      malignancies did local or distant recurrences develop. CONCLUSIONS: Incidental
      carcinomas were found in 13% of spot localization biopsy specimens obtained for
      suspicious mammographic microcalcifications and have a favorable prognosis.
      Infiltrating lobular carcinomas are more commonly found with incidental
      microcalcifications than with determinate microcalcifications, and incidental
      invasive carcinomas are less likely to be poorly differentiated. The majority of
      malignancies, both determinate and incidental to microcalcifications, are due to
      ductal carcinoma in situ. Incidental malignancies commonly occur adjacent to
      fibrocystic changes and their other pathologic characteristics are not
      significantly different from nonincidental carcinomas. Despite the absence of
      radiographic findings, these patients can be successfully treated with breast
      conservation.

PMID- 11532406
TI  - Free fluid on abdominal computed tomography without solid organ injury after
      blunt abdominal injury does not mandate celiotomy.
AB  - BACKGROUND: Mandatory celiotomy has been proposed for all patients with
      unexplained free fluid on abdominal computed tomography (CT) scanning after blunt
      abdominal injury. This recommendation has been based upon retrospective data and
      concerns over the potential morbidity from the late diagnosis of blunt intestinal
      injury. This study examined the rate of intestinal injury in patients with free
      fluid on abdominal CT after blunt abdominal trauma. METHODS: This study was a
      multicenter prospective series of all patients with blunt abdominal trauma
      admitted to four level I trauma centers over 22 months. Data were collected
      concurrently at the time of patient enrollment and included demographics, injury
      severity score, findings on CT scan, and presence or absence of blunt intestinal
      injury. This database was specifically queried for those patients who had free
      fluid without solid organ injury. RESULTS: In all, 2,299 patients were evaluated.
      Free fluid was present in 265. Of these, 90 patients had isolated free fluid with
      only 7 having a blunt intestinal injury. Conversely, 91% of patients with free
      fluid did not. All patients with free fluid were observed for a mean of 8 days
      (95% confidence interval 6.1 to 10.4, range 1 to 131). There were no missed
      injuries. CONCLUSIONS: Free fluid on abdominal CT scan does not mandate
      celiotomy. Serial observation with the possible use of other adjunctive tests is
      recommended.

PMID- 11532407
TI  - Lessons learned from laparoscopic gastric banding for morbid obesity.
AB  - BACKGROUND: Laparoscopic gastric banding is a minimally invasive bariatric
      operation that is increasing in popularity at many centers worldwide. Although
      this procedure is not yet approved in the United States, clinical trials are
      ongoing. METHODS: We report our results of a 3-year follow-up on 60 patients who
      underwent the laparoscopic gastric band procedure for the treatment of morbid
      obesity. The procedure was performed at the Wesley Obesity Clinic in Brisbane,
      Australia. RESULTS: At follow-up, 51 of the 60 patients (85%) still had the
      laparoscopic gastric band in place. All of the patients had a lower body weight
      after undergoing the procedure. The average weight loss was 39 kg (range 2 to 98
      kg), representing a loss of 65% of average excess body weight. Twenty-five of 51
      patients (49%) regained some weight after their initial loss, but the average
      amount was only 5 kg. The remaining 26 patients have remained at their lowest
      body weight recorded after the procedure or are continuing to lose weight. There
      was no operative mortality. Complications predominantly were caused by band
      slippage (21%), which has been nearly eliminated in recent practice (1 slip in
      the last 225 cases). Subsequent modifications in the technique to prevent band
      slippage included placing the band near the level of the esophagus, with minimal
      disruption of the posterior gastric attachments and diligent suturing of the band
      in place. CONCLUSIONS: We conclude that the laparoscopic gastric band is
      effective in short- and long-term weight loss. The high rate of reoperation for
      repositioning has been avoided in current practice.

PMID- 11532408
TI  - Normocalcemia with elevated parathyroid hormone levels after surgical treatment
      of primary hyperparathyroidism.
AB  - BACKGROUND: Thirty percent of patients who undergo successful parathyroidectomy
      for primary hyperparathyroidism show unexplained elevated postoperative serum
      parathyroid hormone (PTH) levels despite normocalcemia. METHODS: PTH levels were
      measured monthly in 97 patients for 6 months after parathyroidectomy. Renal
      function, 25-OH-vitamin D levels, serum alkaline phosphatase levels, osteocalcin,
      and bone densitometry were evaluated before and 6 months after surgery. PTH
      reactivity to calcium loading was tested at the sixth month. RESULTS: Thirty
      patients had elevated PTH levels despite normocalcemia after parathyroidectomy.
      Before surgery, these 30 patients had higher PTH and creatinine levels, lower
      vitamin D levels, and more extensive bone involvement than those with normal
      postoperative PTH levels. In patients with normal renal function and normal
      vitamin D levels, postoperative PTH values correlated with preoperative PTH
      levels but not with bone disease. CONCLUSION: In most cases, elevated PTH levels
      after surgery is an adaptive reaction to renal dysfunction or vitamin D
      deficiency. If no adaptive cause can be found, persistent hyperparathyroidism
      must be suspected.

PMID- 11532410
TI  - Feasibility, reliability and validity of a new assessment form for use with basic
      surgical trainees.
AB  - BACKGROUND: To establish feasibility, reliability and validity of a newly
      designed basic surgical training (BST) assessment form. METHODS: The assessment
      form was evaluated among trainees on the South-east Scotland BST rotation over 18
      months. Feasibility was indicated by response rate. Reliability was determined
      using test-retest analysis and internal consistency of each domain determined by
      Cronbach's alpha and item-total correlation. Construct validity was evaluated by
      determining improvement in performance after 1 year of training. RESULTS:
      Response rate was high (889 of 984 forms [90%]), with similar representation from
      all disciplines. A highly significant positive correlation was found between test
      retest scores for all domains (rho: I, 0.736; II, 0.875; III, 0.671; IV, 0.826;
      V, 0.859; P = 0.0001 all domains, Spearman's). Internal consistency was excellent
      for each domain, with Cronbach's alpha ranging from 0.82 to 0.95. Item-total
      correlation coefficients were greater than the required 0.4 for all but one task.
      In 101 assessments carried out after 1 year of training, significant improvement
      in scores was found for all domains except clinical skills (time 0 to time 1 year
      median [interquartile range]: I, 81 [26 to 100] to 100 [100 to 100], P = 0.008;
      II, 17 [-19 to 52] to 72 [36 to 100], P = 0.015; III, 85 [51 to 100] to 100 [87
      to 100], P = 0.018; IV, 82 [44 to 100] to 92 [69 to 100], P = 0.211; V, 27 [-33
      to 64] to 76 [32 to 100], P = 0.004). CONCLUSIONS: The new assessment form is
      feasible, reliable and valid and would therefore be suitable for extended use
      with basic surgical trainees.

PMID- 11532409
TI  - Teaching students to break bad news.
AB  - BACKGROUND: Physicians typically learn to communicate bad news to patients
      through trial and error or observation of more senior physicians. To give medical
      students initial instruction and experience in this area, we developed two
      standardized patient instructor (SPI) experiences in "breaking bad news."
      METHODS: Twenty-one junior medical students had an SPI experience discussing a
      new diagnosis of rectal cancer or pregnancy loss. These 21 students, and 17
      students having neither experience, interviewed the pregnancy loss SPI on the
      clinical performance examination (CPE) at the end of the junior year. RESULTS:
      Students who had previously had a "breaking bad news" SPI experience performed
      significantly better on the CPE pregnancy loss station than students without this
      experience. There was no significant difference in performance between students
      who had previously had the pregnancy loss versus rectal cancer SPI. CONCLUSIONS:
      This research provides evidence for the effectiveness of bad news communication
      skills teaching, and its potential for transfer across content areas.

PMID- 11532411
TI  - The performance of master surgeons on standard aptitude testing.
AB  - BACKGROUND: Identification of the desired psychomotor abilities of optimal
      surgical performance, if possible, would be useful in the selection of surgical
      trainees. The aim of this study was to determine the level of these abilities
      among endoscopic consultant surgeons held in high regard by their peers. METHODS:
      Twenty endoscopic consultant "master" surgeons were tested on three aptitude
      tests: the Gibson Spiral Maze Test (error score measures eye-hand coordination),
      the Crawford Small Parts Dexterity Test (execution time indicates manual
      dexterity), and the Space Relations Test (correct scores reflect visuo-spatial
      ability). Their performance was compared with that of 20 medical students and the
      reference norm as provided by the tests' manuals. RESULTS: The median scores of
      master surgeons fell in the 20th, 24th, and 30th percentiles, whereas the scores
      of medical students fell in the 50th, 20th, and 65th percentile of norm reference
      for the Gibson Spiral Maze, Crawford Small Parts Dexterity, and Space Relations
      tests, respectively. The master surgeons enacted significantly fewer errors
      (Gibson Spiral Maze), had similar execution times (Crawford Small Parts
      Dexterity), and lower visuo-spatial scores (Space Relations) than medical
      students. CONCLUSION: The level of eye-hand coordination and manual dexterity of
      master surgeons was found to be higher than that of the average norm including
      medical students, while their visuo-spatial ability was lower.

PMID- 11532412
TI  - Discussion of death and dying in surgical textbooks.
AB  - BACKGROUND: Quality end-of-life care is an increasing concern for the public and
      the medical profession. Surgical textbooks could serve as an important
      educational and reference resource to improve this care. METHODS: Four general
      surgical textbooks were scored for helpful information on death and dying for
      eight surgical diseases. For each disease, nine content domains related to care
      of the dying patient were evaluated. Three texts included a chapter on cancer
      that was evaluated separately. RESULTS: Disease epidemiology,
      prognosis/prevention, progression, and medical interventions were generally well
      discussed in all textbooks. However, little helpful information was provided with
      regards to breaking bad news/advanced care planning, mode of death, treatment
      decision-making, effect on family/surgeon, and symptom management. Cancer
      chapters also addressed only a few of these concerns. CONCLUSION: Death and the
      dying patient are sufficiently frequent in surgical practice that it would be
      appropriate to increase the amount of information provided.

PMID- 11532413
TI  - Intraoperative sentinel lymph node mapping in patients with colon cancer.
AB  - BACKGROUND: The sentinel lymph node (SLN) mapping technique has been used in
      breast cancer and melanoma, and was recently described for colon cancer. METHODS:
      Thirty-five patients with colon cancer underwent intraoperative SLN mapping. One
      milliliter of 1% isosulfan blue was injected subserosally around the tumor. The
      first nodal area that was highlighted with blue was identified as the SLN. All
      lymph nodes underwent examination with hematoxylin and eosin (H&E) stain. SLNs
      underwent additional sectioning and were stained with CAM 5.2. RESULTS: Lymphatic
      mapping adequately identified the SLN in 25 patients (71%). In the 15 cases where
      the SLNs were negative for metastases, all other non-SLNs were also negative (0%
      false negative rate). The SLN was the only site of metastases in 6 (17%) of 35
      patients. CAM 5.2 staining provided the only evidence of micrometastases in 4
      (11%) of 35 patients. CONCLUSIONS: Intraoperative SLN mapping is a feasible
      technique with a reasonable SLN identification rate (71%). The absence of
      metastases in the SLNs accurately predicts the status of the non-SLNs. Tumors in
      11% of patients were upstaged by the demonstration of micrometastatic
      involvement, and these patients may benefit from further adjuvant chemotherapy.

PMID- 11532414
TI  - A reappraisal of a modified through-knee amputation in patients with peripheral
      vascular disease.
AB  - BACKGROUND: Through-knee amputation provides a longer lever arm and improved
      muscle control of the limb compared with above-knee amputation. Through-knee
      amputation also allows use of a total end-bearing prosthesis, which avoids the
      ischial pressure and suspension belts required of the above-knee amputation
      prosthesis. Several reports in the European literature tout the superiority of
      the through-knee amputation over the above-knee amputation in the patient with
      vascular disease. Through-knee amputation has received little attention in the
      United States, however, owing to the belief that the long flaps necessary to
      close a standard through-knee amputation are associated with an unacceptable rate
      of wound problems and offer no functional ambulatory advantage to above-knee
      amputation. We reviewed our experience with a modified technique of through-knee
      amputation in a group of patients with severe lower extremity ischemia who were
      not candidates for below-knee amputation to determine the incidence of wound
      complications and their functional outcome. METHODS: Since 1996, 12 patients with
      severe lower extremity arterial insufficiency have undergone through-knee
      amputation utilizing a technique designed to limit flap length and facilitate the
      fit of a suction prosthesis. Two patients died of myocardial infarction in the
      immediate postoperative period and were excluded from the study. In the remaining
      10 patients (1 man, 9 women; mean age 63 years (range 40 to 86), the below-knee
      amputation level was precluded because of gangrene or nonhealing wounds of the
      mid leg in 5 patients, failure of a previous below-knee amputation attempt in 4
      patients, and severe ischemia that would compromise below-knee amputation healing
      in 1 patient. Nine patients had at least one failed vascular reconstruction
      procedure. RESULTS: Mean follow-up is 25 months (range 6 to 41). Six (60%)
      patients had primary healing of their amputations. Two (20%) patients had delayed
      healing (6 weeks and 8 weeks). Two (20%) patients developed wound infections,
      which required amputation revision to the above-knee level. Seven (70%) patients
      were fitted with a suction socket prosthesis and are fully ambulatory. One
      patient healed but has not ambulated because of ischemia and subsequent
      ulceration of the contralateral limb. CONCLUSIONS: These data show that through
      knee amputation is associated with an acceptable primary healing rate (80%) and
      satisfactory functional outcomes (70% ambulation) in a high-risk vascular
      population. The functional advantages of through-knee amputation over above-knee
      amputation make it the preferred alternative for patients with vascular disease.

PMID- 11532415
TI  - Teleconsultation before chemotherapy for recently operated on patients.
AB  - BACKGROUND: Some operated on cancer patients require specialized complementary
      chemotherapy. Often, this takes place in another institution, where the patient
      consults the medical oncologist before hospitalization. The aim of this study was
      to analyze the potential benefit of a videoconference consultation within this
      framework. METHODS: Sixteen operated on cancer patients hospitalized in the
      Surgical Unit received a teleconsultation in the presence of their surgeon and
      with the chemotherapist at some distance. During this period, the modalities of
      chemotherapy proposed, the duration of the teleconsultation, the economy of
      transport, and so on were noted. Twenty-four hours later each patient filled in a
      questionnaire aimed at, one, evaluating the quality of the image on an visual
      analogue scale (VAS) and the potential inconvenience involved; and two,
      evaluating the index of patient satisfaction on VAS. Furthermore, the last 12
      patients filled in a questionnaire adapted to each of them, according to the
      information they had received. Each correct answer was noted 1, and each
      incorrect answer was noted 0. A memorization percentage was deduced. RESULTS: The
      average age of the 16 patients was 63.4 years (range 46 to 78). The average
      duration of the teleconsultation was 27 minutes (12 to 40). The index of image
      satisfaction was 61.3%. As for the last 12 patients, 9.8 questions (7 to 12)
      enabled the calculation at 24 hours of the percentage of data retained by the
      patient (memorization index) based on the modalities and consequences of the
      chemotherapy. The percentage of correct answers was 80.5%. Fourteen of the 16
      patients considered that teleconsultation had its advantages. Two patients would
      have preferred a classic consultation. The global satisfaction index was 79.9%.
      The average cost of functioning per patient was 187.76 FF A saving in transport
      of 509.92 FF was recorded per patient. CONCLUSIONS: In the context of this
      original study, teleconsultation neither altered the doctor-patient relationship
      nor the quality of the message transmitted. Furthermore, it encourages closer
      links between complementary teams working at a distance and multidisciplinarity
      in cancerology.

PMID- 11532416
TI  - A new biliodigestive anastomosis technique to prevent reflux and stasis.
AB  - BACKGROUND: The Roux-en-Y procedure for biliodigestive drainage is most widely
      accepted, but 10% to 15% of patients postoperatively suffer from a blind-loop
      syndrome or cholangitis due to motility disorders. A new biliodigestive technique
      is evaluated in a rat model to prevent these complications. METHODS: This
      experimental study in Wistar rats compares the Roux-en-Y technique with a new
      biliodigestive anastomosis creating a jejunal loop with luminal occlusion.
      Clinical parameters, small bowel motility, bacteriologic growth, and liver
      histopathology were evaluated in native and postoperative animals within a study
      period of 180 days. RESULTS: Both operative procedures were well tolerated. After
      6 months intense fibrosis of the liver and high-grade purulent cholangitis were
      observed in animals in the Roux-en-Y group. In these animals enterobacter and
      enterococci overgrowth was found. Myoelectric small bowel recordings revealed
      significant impairment of slow-wave frequency, aboral velocity, and action
      potentials (percentage of phase III) in Roux-en-Y animals. CONCLUSIONS: Motility
      disorders after conventional Roux-en-Y biliodigestive anastomosis are pivotal for
      histomorphological damage and infectious findings and can be prevented by using
      the new technique to create a jejunal loop with luminal occlusion.

PMID- 11532417
TI  - Effect of fibrin glue occlusion of the hepatobiliary tract on thioacetamide
      induced liver failure.
AB  - BACKGROUND: Expression and activation of hepatocyte growth factor (HGF) is
      stimulated by a complex system of interacting proteins, with thrombin playing an
      initial role in this process. The impact of temporary occlusion of the
      hepatobiliary tract with fibrin glue (major component thrombin) on the HGF system
      in acute and chronic liver damage in a rat model was investigated. METHODS:
      Chronic liver damage was induced in 40 rats by daily intraperitoneal application
      of thioacetamide (100 mg/kg) for 14 days. After 7 days half of them received an
      injection of 0.2 mL fibrin glue into the hepatobiliary system. Daily
      intraperitoneal administration of thioacetamide continued for 7 consecutive days.
      The rats were then sacrificed for blood and tissue analysis. Acute liver failure
      was induced in 12 rats by intraperitoneal administration of a lethal dose of
      thioacetamide (500 mg/kg per day for 3 days) after an injection with 0.2 mL
      fibrin glue into their hepatobiliary tract. Survival rates and histological
      outcome were investigated and compared with control animals. RESULTS: Fibrin glue
      occluded rats showed significantly lower liver enzyme activities and serum levels
      of bilirubin, creatinine and urea nitrogen. Immunohistochemistry revealed a
      significant increase in c-met-, HGFalpha- and especially HGFbeta-positive cells.
      Rats subjected to a lethal dose of thioacetamide survived when fibrin glue was
      applied 24 hours prior to the toxic challenge. These animals showed normal liver
      structure and no clinical abnormalities. CONCLUSION: Fibrin glue occlusion of the
      hepatobiliary tract induces therapeutic and prophylactic effects on chronic and
      acute liver failure by stimulating the HGF system. Therefore, fibrin glue
      occlusion might be useful in treating toxic liver failure.

PMID- 11532418
TI  - Randomised controlled trial between stapled circumferential mucosectomy and
      conventional circular hemorrhoidectomy in advanced hemorrhoids with external
      mucosal prolapse.
AB  - BACKGROUND: This randomized prospective study compared the outcome of circular
      hemorrhoidectomy according to the Hospital Leopold Bellan (HLB) technique (Paris)
      with Longo stapled circumferential mucosectomy (LSCM) in two homogeneous groups
      of patients affected by circular fourth-degree hemorrhoids with external mucosal
      prolapse. METHODS: From December 1996 to December 1999, 80 consecutive patients
      with fourth-degree hemorrhoids and external mucosal prolapse were randomly
      assigned to two groups. Forty patients (group A: 18 men, 22 women, mean age 50.5
      years, range 21 to 82) underwent HLB hemorrhoidectomy, and 40 patients (group B:
      15 men, 25 women, mean age 51.0 years, range 29 to 92) underwent LSCM. Before
      surgery, all patients were selected with a standard questionnaire for symptom
      evaluation, full proctological examination, flexible rectosigmoidoscopy, dynamic
      defecography, and anorectal manometry. No significant differences among the two
      groups were found. All patients were controlled with follow-up questionnaire and
      with clinical examination at 1, 2, 4, 12, and 54 weeks after the operation. A
      postoperative manometry was performed 3 months after surgery. RESULTS: The length
      of the operation was significantly lower in group B (25 +/- 3.1 SD versus 50 +/-
      5.3 minutes, P <0.001). Mean hospital stay was 3 +/- 0.4 days in group A and 2 +/
      0.5 days in group B (P <0.01). Mean duration of inability to work was 8 +/- 0.9
      days in group B and 15 +/- 1.4 days in group A (P <0.001). Postoperative pain was
      significantly lower in group B (P <0.001). Mean length of follow-up was 20 +/-
      8.0 months in group A and 20 +/- 7.8 months in group B. Late complications were
      similar in the two groups, with 0%, at present, recurrence rate. CONCLUSIONS: Our
      results confirm that both operations are safe, easy to perform, and effective in
      the treatment of advanced hemorrhoids with external mucosal prolapse. However,
      the LSCM seems to be preferable owing to the fewer postoperative complications,
      easier postoperative management, and shorter time to return to work. A longer
      follow-up is required to confirm the true efficacy of this surgical method.

PMID- 11532419
TI  - Radical, ambulatory hemorrhoidectomy under local anesthesia.

PMID- 11532420
TI  - Insulinoma of the pancreas.

PMID- 11532421
TI  - Aortoenteric fistula.

PMID- 11532422
TI  - Novel applications of Endo GIA linear staplers during pancreaticoduodenectomy and
      total pancreatectomy.
AB  - Pancreaticoduodenectomy and total pancreatectomy remain a formidable challenge to
      many surgeons. This report describes the utilization of Endo GIA linear staplers
      for division of the proximal jejunal mesentery and division of the uncinate
      process during pancreatic surgery. Their use may help to reduce undue bleeding
      during surgery, reduce total operative time, and ultimately reduce postoperative
      morbidity and mortality.

PMID- 11532423
TI  - Is a proliferation index of cancer cells a reliable prognostic factor after
      hepatectomy in patients with colorectal liver metastases?
AB  - BACKGROUND: In spite of many reports focusing on prognostic factors after
      hepatectomy in patients with colorectal liver metastases, few studies have
      investigated pathological factors, eg, fibrous pseudocapsulation, growth pattern
      at the tumor margin, and proliferation activity of cancer cells, other than
      histological type and surgical margin. The aim of the present study was to
      investigate whether absence of pseudocapsulation, infiltrative growth pattern of
      metastases, and higher proliferation of cancer cells shown by Ki-67
      immunohistochemical reactivity were associated with poorer survival after
      hepatectomy among patients with colorectal liver metastases. METHODS: Between
      1988 and 1998, 221 patients underwent hepatic resection of colorectal metastases
      with curative intent in our institution. Pathology analyses were focused on
      pseudocapsulation of liver metastases, growth pattern at the tumor edge, and Ki
      67 labelling index (Ki-67 LI) of cancer cell nuclei. Univariate analyses of
      survival and of disease-free survival were performed for several
      clinicopathological factors, and multivariate analyses of survival and disease
      free survival were also performed. RESULTS: The univariate survival analyses
      showed that pseudocapsulation, growth pattern, and Ki-67 LI were significant
      prognostic factors, besides synchronous versus metachronous occurrence of
      metastases, carcinoembryonic antigen level before hepatectomy, and number of
      metastases. A multivariate analysis showed that Ki-67 labeling index was the most
      reliable prognostic factor of survival. In addition, Ki-67 LI and microscopic
      growth pattern were multivariately predictive factors of disease-free survival.
      CONCLUSIONS: This large single-institution study showed that investigation of
      cancer cell proliferation and pathologic characteristics of the tumor margin are
      major prognostic factors.

PMID- 11532424
TI  - Influence of gender on intraluminal thrombus of abdominal aortic aneurysms.
AB  - BACKGROUND: The mechanisms of formation of intraluminal thrombus (ILT) of
      abdominal aortic aneurysms (AAA) remain unknown. The aim of this study was to
      investigate the pathogenesis of AAA by analysis of ILT. METHODS: We
      retrospectively analyzed the size of ILT in 98 consecutive patients with AAA
      undergoing abdominal computed tomography (CT) examination. The volume of ILT was
      estimated by the area ratio of ILT in CT images. Important baseline variables
      related to small ILT were determined using logistic-regression analysis. RESULTS:
      There were two apparent peaks in the distribution of ILT ratio. Thirteen of 98
      patients had negligible ILT with ratio < or = 0.1. Female gender was the only
      patient characteristic independently significantly correlated with small ILT
      (odds ratio 5.214, P = 0.0096). CONCLUSION: Our findings provide important
      evidence that AAA is formed by at least two different pathogenic processes. It is
      likely that this difference in mechanisms may be caused partly by sex hormones.

PMID- 11532425
TI  - Clinical applications and techniques of cinedefecography.
AB  - BACKGROUND: Cinedefecography is of value in routine examination of functional
      disorders of the pelvic floor. Interest in this technique has rapidly expanded
      owing to the increased availability of colorectal physiologic testing and better
      understanding of the multifactorial pathophysiology involving evacuation
      disorders. METHODS: A summary of the available techniques, methodology, and
      indications for cinedefecography was undertaken. In addition, information was
      provided on interpretation of these images particularly in the context of
      anatomic abnormalities and clinical applications. RESULTS: Cinedefecography can
      be rapidly and easily performed using standard radiographic equipment. Effective
      radiation dose is significantly lower than for other intestinal contrast studies.
      The technique has been found most useful for measurements of perineal descent,
      puborectalis length, and ascertaining the function of the puborectalis muscle and
      pelvic floor. Common diagnoses that can be made by this test include nonrelaxing
      puborectalis syndrome, perineal descent, rectocele, enterocele, sigmoidocele, and
      rectoanal intussusception. CONCLUSION: Cinedefecography provides a wide range of
      information to assist the surgeon with the evaluation and management of patients
      with evacuatory and other associated pelvic floor disorders.

PMID- 11532426
TI  - Extensive neuronal localization and neurotrophic function of fibroblast growth
      factor 8 in the nervous system.
AB  - Fibroblast growth factor (FGF) 8 has been well established to play a critical
      role in the early development of the central nervous system (CNS). We report here
      extensive neuronal localization and neurotrophic function of FGF8 in the nervous
      system. In sections of mouse embryos at E10.5, FGF8 was immunohistochemically
      found in neurons at the marginal zones of the CNS and in the dorsal root ganglia
      (DRG). Neuronal localization of FGF8 was marked at later embryonic stages and in
      adults, involving most of the central and peripheral neurons, including
      intermuscular enteric neurons, DRGs, and paraaortic sympathetic ganglia.
      Functionally, FGF8 promoted neurite outgrowth in human neuroblastoma SK-N-MC
      cells as well as in rat pheochromocytoma PC12 cells, suggesting that FGF8 acts as
      a neurotrophic factor. FGF8 also supported neuronal survival and differentiation
      in cultured human neural progenitor cells. In a cell growth assay, treatment with
      50 ng/ml FGF8 on human cultured neuroblastoma SK-N-MC and IMR32 cells attenuated
      the growth of both. In accordance with these in vitro findings, the
      immunohistochemical analysis on human neurological diseases showed that FGF8
      expression is evident in differentiating histological types of neuroblastoma and
      ganglioneuroblastoma, and that the levels of FGF8 immunoreactivity in the
      substantia nigra from Parkinson's disease are significantly lower than those in
      age-matched controls. Taken together, the present findings strongly suggest that
      FGF8 acts as a more generalized neurotrophic factor than previously reported.

PMID- 11532427
TI  - Dentate granule neuron apoptosis and glia activation in murine hippocampus
      induced by trimethyltin exposure.
AB  - We investigated the effect of trimethyltin (TMT), a well-known neurotoxicant, on
      murine hippocampal neurons and glial cells. Three days following intraperitoneal
      (i.p.) injection of TMT into 1-month-old Balb/c mice at a dose of 2.5 mg/kg body
      weight we detected damage of the dentate gyrus granular neurons. The dying cells
      displayed chromatin condensation and internucleosomal DNA fragmentation, which
      are the most characteristic features of apoptosis. To study, if prolyl
      oligopeptidase is engaged in neuronal apoptosis following TMT administration, we
      pretreated mice with the specific inhibitor--Fmoc-Pro-ProCN in doses of 5 and 10
      mg/kg body weight (i.p. injection). Three days following injection we did not
      observe any attenuation of neurotoxic damage, regardless of inhibitor dose,
      indicating the lack of prolyl oligopeptidase contribution to neuronal injury
      caused by TMT. The neurodegeneration was associated with reactive astrogliosis in
      whole hippocampus, but particularly in injured dentate gyrus. The reactive
      astrocytes showed an increased nerve growth factor (NGF) expression in ventral as
      well as dorsal hippocampal parts. NGF immunoreactivity was also augmented in
      neurons of CA3/CA4 areas, which were almost totally spared after TMT
      intoxication. It suggested a role for this neurotrophin in protection of
      pyramidal cells from loss of connection between CA3/CA4 and dentate gyrus fields.
      The granule neurons' death was accompanied by increased histochemical staining
      with isolectin B4, a marker of microglia, in the region of neurodegeneration. The
      microglial cells displayed ramified and ameboid morphology, characteristic of
      their reactive forms. Activated microglia were the main source of interleukin
      1beta (IL-1beta). It is possible that this cytokine may participate in
      neurodegeneration of granule cells. Alternatively, IL-1beta elaborated by
      microglia could play a role in increasing NGF expression, both in astroglia and
      in CA3/CA4 neurons.

PMID- 11532428
TI  - Progressive brain dysfunction following intracerebroventricular infusion of
      beta(1-42)-amyloid peptide.
AB  - The behavioral, neurochemical and histological changes of rats subjected to 3
      days treatment with intracerebroventricular infusion of beta-amyloid
      peptides(Abeta)(1-42) were investigated 20 days and 80 days after the surgery.
      Abeta(1-42) produced a dose-dependent and a time-dependent impairment in the
      spontaneous alternation performance in the Y-maze (spatial working memory), place
      navigation task in a water maze (spatial reference memory) and passive avoidance
      retention (non-spatial long-term memory) at doses of 10 and 20 microg/rat. The
      learning impairments were more severe at 80 days than 20 days after infusion of
      Abeta(1-42). At 25 days after the infusion, a significant decrease in
      hemicholinium-3 (HC-3) binding was observed only in the hippocampus, although
      choline acetyltransferase (ChAT) activity was unchanged in the brain regions
      tested as compared with the vehicle (Abeta(40-1)) treatment. In contrast, the
      reduction in ChAT activity 85 days after Abeta(1-42) infusion was significant in
      hippocampus and striatum. HC-3 binding was also significantly decreased in the
      posterior cortex, hippocampus and striatum. In the histological analysis, brain
      atrophy was observed inasmuch as ventricular enlargement and neuronal damage in
      the CA1 area of the hippocampus were seen 85 days after Abeta(1-42) infusion.
      These results suggest that the rats subjected to intracerebroventricular infusion
      of Abeta(1-42) suffered from progressive brain dysfunction, and could be useful
      as an animal model for evaluating the developmental processes at the early and/or
      middle stage of Alzheimer's-type dementia.

PMID- 11532430
TI  - Glucocorticoid effects on Fos immunoreactivity and NADPH-diaphorase histochemical
      staining following spinal cord injury.
AB  - Glucocorticoids (GC) provide neuroprotection and early recovery after spinal cord
      injury (SCI). While several mechanisms were proposed to account for these
      effects, limited information exists regarding GC actions in sensory areas of the
      spinal cord. Presently, we studied the time course of Fos expression, and reduced
      nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemical
      staining to monitor neuronal responses to SCI with or without GC treatment. Rats
      with sham-operation or transection at the thoracic level (T7-T8) received vehicle
      or 5 mg/kg of the GC dexamethasone (DEX) at 5 min post-lesion and were sacrificed
      2 or 4 h after surgery. Another group of SCI rats received vehicle or intensive
      DEX treatment (5 min, 6 h, 18 h and 46 h post-lesion) and were sacrificed 48 h
      after surgery. The number of NADPH-d positive neurons or Fos immunoreactive
      nuclei was studied by computer-assisted image analysis in superficial dorsal horn
      (Laminae I-III) and central canal area (Lamina X) below the lesion. While
      constitutive Fos immunoreactive nuclei were sparse in controls, SCI increased Fos
      expression at 2 and 4 h after injury. DEX treatment significantly enhanced the
      number of Fos positive nuclei in Laminae I-III by 4 h after transection, although
      the response was not maintained by intensive steroid treatment when tested at 48
      h after SCI. NADPH-d positive neurons in Laminae I-III increased at 2 and 4 h
      after SCI while a delayed increased was found in central canal area (Lamina X).
      DEX treatment decreased NADPH-d positive neurons to sham-operated levels at all
      time points examined. Thus, while GC stimulation of Fos suggests activation of
      neurons involved in sympathetic outflow and/or pain, down-regulation of NADPH-d
      indicates attenuation of nociceptive outflow, considering the role of enzyme
      derived nitric oxide in pain-related mechanisms. Differential hormonal effects on
      these molecules agree with their localization in different cell populations.

PMID- 11532429
TI  - Localisation of endothelin-1 mRNA expression and immunoreactivity in the retina
      and optic nerve from human and porcine eye. Evidence for endothelin-1 expression
      in astrocytes.
AB  - We have investigated the localisation of endothelin-1 (ET-1) mRNA and ET-1-like
      immunoreactivity in retina and anterior portion of optic nerve from human and
      porcine eyes. In situ hybridisation method revealed expression of ET-1 mRNA
      mainly in the innermost layers of the retinas, in the retinal pigment epithelium
      cells as well as in the astrocytes of the optic nerve. Immunohistochemical
      studies showed that ET-1-like immunoreactivity appeared in the same regions where
      ET-1 mRNA was expressed as well as in the inner nuclear layer and in the inner
      segments of photoreceptors. In the nerve fibre and ganglion cell layers,
      astrocytes expressed both glial fibrillary acidic protein and ET-1 proteins
      suggesting that these cells may secrete ET-1. Expression of ETA and ETB receptors
      in human retina were demonstrated by reverse transcription-polymerase chain
      reaction. Our results demonstrated expression of ET-1 in glial, neural and
      vascular components of retina and optic nerve from human and porcine eyes.

PMID- 11532431
TI  - Abnormal iron accumulation in the brain of neonatal hypotransferrinemic mice.
AB  - Transferrin is a plasma protein involved in iron delivery to tissues. To study
      iron transport into the brain under a transferrin deficiency, iron concentration
      and 59Fe uptake in the brain were measured in neonatal hypotransferrinemic (HP)
      mice at 7 days of age. Brain iron concentration of the HP mice, in which iron
      concentration was relatively high in the cerebral cortex and cerebellum, was
      approximately three times higher than that of non-mutant mice, whereas serum iron
      concentration of HP mice was significantly lower than that of non-mutant mice.
      When 59FeCl3 was subcutaneously injected into HP and non-mutant mice, 59Fe was
      distributed highly in the choroid plexus in the ventricles of HP mice 24 h after
      injection. The 59Fe distribution in the brain was different between HP and non
      mutant mice. On the other hand, the clearance of 59Fe from the blood was very
      high in HP mice and the hepatic 59Fe concentration of HP mice was more than ten
      times of that of non-mutant mice. The present findings demonstrate that iron
      distribution in the brain is changed by transferrin deficiency and that iron
      abnormally accumulates in the brain of HP mice. It is likely that the management
      of iron is different in the brain of HP mice.

PMID- 11532432
TI  - Discrete regions in the laterodorsal tegmental area of the rat regulating the
      urinary bladder and external urethral sphincter.
AB  - In urethane anesthetized rats, the laterodorsal tegmental area was stimulated
      systematically with a carbon fiber electrode to clarify regions regulating the
      urinary bladder and/or the external urethral sphincter. Contraction of the former
      was monitored by bladder pressure and that of the latter by electromyogram.
      Stimulation of a small area around the ventrolateral edge of the central gray in
      a plane at the junction of the mesencephalon and pons, where cholinergic neurons
      in the laterodorsal tegmental nucleus formed the largest mass, induced
      contraction only of the bladder. Arranged in tandem rostrocaudally with this
      bladder site, a very small area whose stimulation induced contraction only of the
      sphincter was found also at the ventrolateral edge of the central gray in a plane
      slightly caudal to the above. Slightly lateral and caudal to this sphincter site,
      there were sites the stimulation of which induced contraction of both the bladder
      and sphincter. It was thus shown physiologically that there were discrete sites
      in the laterodorsal tegmental area regulating the bladder and sphincter
      independently.

PMID- 11532433
TI  - Peripheral nitric oxide in carrageenan-induced inflammation.
AB  - Recent studies have suggested that nitric oxide (NO) peripherally produced by
      different nitric oxide synthase (NOS) isoforms contributes to edema formation and
      development of hyperalgesia. The present study was designed to examine the
      effects of NOS isoforms on NO release in carrageenan-induced inflammation at
      various time points. A microdialysis probe was implanted subcutaneously into the
      glabrous skin of hindpaws of Sprague-Dawley rats under pentobarbital anesthesia.
      After sample collection to obtain the basal level of the total amount of nitrite
      and nitrate (NO2-/NO3-), modified Ringer solution, a non-selective NOS inhibitor,
      NG monomethyl-L-arginine acetate (L-NMMA), or an iNOS inhibitor, aminoguanidine
      hemisulfate (AG) was perfused through the microdialysis probe. 2 mg of
      carrageenan was injected into the plantar surface of the probe-implanted hindpaw.
      Carrageenan was also injected in rats that had undergone sciatic nerve
      sectioning. Carrageenan significantly increased the dialysate concentrations of
      NO2-/NO3- for more than 8 h. L-NMMA suppressed the carrageenan-induced increase
      in NO2-/NO3- concentration. Although AG did not suppress the increase in NO2-/NO3
      for the first 2 h after carrageenan injection, significant suppression of the
      increase in NO2-/NO3- was observed from 2.5 h after carrageenan injection. In the
      rats in which the sciatic nerves had been denervated, the increases in
      concentrations of NO2-/NO3- were completely suppressed up to 3 h and partially
      suppressed 4.5-8 h after carrageenan injection. The results of the current study
      show that carrageenan induces peripheral release of NO, the production of which
      is mediated by nNOS in the early phase and by both nNOS and iNOS in the late
      phase of carrageenan-induced inflammation.

PMID- 11532434
TI  - Effect of orally administered guanosine on seizures and death induced by
      glutamatergic agents.
AB  - Intraperitoneal guanosine has been shown to prevent quinolinic acid-induced
      seizures in mice. In this study, we investigated the effect of orally
      administered guanosine on seizures induced by the glutamate agonists quinolinic
      acid and kainate, and the endogenous glutamate releaser alpha-dendrotoxin.
      Guanosine (7.5 mg/kg, per os), administered 75 min in advance, prevented 70% of
      seizures induced by i.c.v. quinolinic acid, being as efficient as the NMDA
      channel blocker MK-801 administered intraperitoneally. Guanosine was ineffective
      against kainate-induced seizures, but significantly reversed the potentiation of
      seizures and death caused by the concomitant injection of MK-801. Guanosine also
      significantly prevented seizures and death induced by i.c.v. alpha-dendrotoxin,
      whereas MK-801 and phenobarbital only prevented death. Altogether, our findings
      underscore the therapeutic potential of oral administration of guanosine for
      treating diseases involving glutamatergic excitotoxicity, including epilepsy.

PMID- 11532436
TI  - Circadian activity of the GABAergic system in the golden hamster retina.
AB  - Daily changes in gamma-aminobutyric acid (GABA) turnover rate were studied in the
      golden hamster retina. This parameter showed significant variations throughout
      the light-dark cycle, with minimal values during the day. Retinal glutamic acid
      decarboxylase (GAD) activity was higher at midnight than at noon. Moreover,
      [3H]GABA binding significantly varied throughout the 24-h cycle, with maximal
      values during the day. Saturation studies performed at 12:00 and 24:00 h
      indicated that the maximal concentration of [3H]GABA binding sites (Bmax) was
      significantly higher at noon, whereas the dissociation constant (Kd) remained
      unchanged. High K+-induced GABA release was significantly higher at midnight than
      at midday. Daily variations in retinal GABA turnover rate, GABA release, and in
      its specific binding persisted in golden hamsters exposed to constant darkness.
      In summary, these results support the idea of a circadian clock-controlled
      GABAergic activity in the hamster retina.

PMID- 11532435
TI  - Dynamic platelet accumulation at the site of the occluded middle cerebral artery
      and in downstream microvessels is associated with loss of microvascular integrity
      after embolic middle cerebral artery occlusion.
AB  - Information is lacking regarding dynamic platelet accumulation at the site of the
      occluded middle cerebral artery (MCA) and the relationship between platelet
      aggregation in downstream cerebral microvessels and loss of perfusion and
      vascular integrity of these microvessels. In the present study, we employed a
      model of embolic MCA occlusion in the rat to simultaneously measure temporal and
      spatial profiles of platelet accumulation at the site of the embolus occluding
      the MCA and within downstream cerebral microvessels. We also measured the
      integrity of microvessels and matrix metalloproteinase (MMP) activity in ischemic
      brain. Rats (n=36) were subjected to embolic MCA occlusion. Immunohistochemistry
      was used to detect microvascular integrity, plasminogen activator inhibitor 1
      (PAI-1) and the deposition of fibrin. SDS-PAGE zymography was used to measure
      MMP2 and MMP9 activities. Accumulation of platelets and increases in PAI-1
      immunoreactivity at the site of the embolus occluding the MCA were detected 1 h
      (n=7) and 4 h (n=7) after ischemia, respectively, and numbers of GPIIb/IIIa
      immunoreactive downstream cerebral microvessels increased significantly (209+/
      59; n=7; P<0.05) 4 h after ischemia, suggesting dynamic platelet aggregation. A
      significant (n=7; P<0.01) diffuse loss of type IV collagen immunoreactivity in
      microvessels was temporally associated with platelet GPIIb/IIIa immunoreactivity
      within the vessels. Triple immunostaining revealed that microvessels containing
      platelet aggregates exhibited loss of type IV collagen immunoreactivity and both
      intra- and extra-vascular fibrin deposition, suggesting that intravascular
      platelet aggregation is associated with decreases in the integrity of the
      microvascular basal lamina and blood-brain barrier leakage. A significant
      increase (P<0.05) in MMP9 was detected at 4 h (n=3) and 24 h (n=3) after ischemia
      but levels of MMP2 were not significantly changed in ischemic brain. Our data
      suggest that dynamic platelet aggregation in ischemic brain may contribute to
      time-dependent resistance to fibrinolysis. In addition, platelet deposition and
      increased MMP9 coincided with degradation of type IV collagen and loss of
      vascular integrity. These data suggest an important role for post-occlusive
      distal platelet deposition in the pathophysiology of stroke.

PMID- 11532437
TI  - Does long-term glucose infusion reduce brain damage after transient cerebral
      ischemia?
AB  - A recent study reported that hyperglycemia of a brief duration worsens, and of
      long duration reduces, ischemic brain damage. To test whether this is a valid
      conception, we induced 10 min of transient forebrain ischemia, recorded
      postischemic seizures, and evaluated brain morphology. The results showed that
      administration of glucose 2 h before ischemia aggravated brain damage, induced
      seizures, and caused animal death in the same manner as was previously observed
      when glucose was given 30 min before ischemia. Thus, the conclusion that the
      influence of glucose on an ischemic transient is dependent upon the duration of
      hyperglycemia is unsubstantiated.

PMID- 11532438
TI  - Topogenesis of membrane proteins: determinants and dynamics.
AB  - For targeting and integration of proteins into the mammalian endoplasmic
      reticulum, two types of signals can be distinguished: those that translocate
      their C-terminal sequence (cleavable signals and signal-anchors) and those that
      translocate their N-terminus (reverse signal-anchors). In addition to the well
      established effect of flanking charges, also the length and hydrophobicity of the
      apolar core of the signal as well as protein folding and glycosylation contribute
      to orienting the signal in the translocon. In multi-spanning membrane proteins,
      topogenic determinants are distributed throughout the sequence and may even
      compete with each other. During topogenesis, segments of up to 60 residues may
      move back and forth through the translocon, emphasizing unexpected dynamic
      aspects of topogenesis.

PMID- 11532439
TI  - Overexpression of mammalian integral membrane proteins for structural studies.
AB  - Recent successes in the determination of atomic resolution structures of integral
      membrane proteins have relied on purifying the proteins from abundant natural
      sources. In contrast, the majority of mammalian receptors, ion channels and
      transporters need to be overexpressed to obtain sufficient material for
      structural studies. This has often proved to be very difficult. Overexpression
      studies on a wide range of mammalian membrane proteins have shown that a few can
      be expressed functionally in bacteria, but many others require an insect or
      mammalian cell host for activity or high level expression. The serotonin
      transporter, which has been expressed in all the major hosts available, is a good
      example that has given insights into the problem of overexpressing mammalian
      membrane proteins for structural studies.

PMID- 11532440
TI  - Semliki Forest virus vectors: efficient vehicles for in vitro and in vivo gene
      delivery.
AB  - Rapidly generated high-titer Semliki Forest virus (SFV) vectors can infect
      numerous mammalian cell lines and primary cell cultures, and result in high
      levels of transgene expression. SFV-based expression of transmembrane receptors
      has been characterized by specific ligand-binding activity and functional
      responses. Adaptation of the SFV technology for mammalian suspension cultures has
      allowed the production of hundreds of milligrams of recombinant receptor for
      purification and structural studies. The same SFV stock solutions used for the
      infection of mammalian cells in culture have also been successfully applied for
      efficient transgene expression in organotypic hippocampal slices, as well as in
      vivo in rodent brain.

PMID- 11532441
TI  - Carbohydrate transporters of the bacterial phosphoenolpyruvate: sugar
      phosphotransferase system (PTS).
AB  - The glucose transporter of Escherichia coli couples translocation with
      phosphorylation of glucose. The IICB(Glc) subunit spans the membrane eight times.
      Split, circularly permuted and cyclized forms of IICB(Glc) are described. The
      split variant was 30 times more active when the two proteins were encoded by a
      dicistronic mRNA than by two genes. The stability and activity of circularly
      permuted forms was improved when they were expressed as fusion proteins with
      alkaline phosphatase. Cyclized IICB(Glc) and IIA(Glc) were produced in vivo by
      RecA intein-mediated trans-splicing. Purified, cyclized IIA(Glc) and IICB(Glc)
      had 100% and 30% of wild-type glucose phosphotransferase activity, respectively.
      Cyclized IIA(Glc) displayed increased stability against temperature and GuHCl
      induced unfolding.

PMID- 11532442
TI  - Atomic structure of a glycerol channel and implications for substrate permeation
      in aqua(glycero)porins.
AB  - The structure of a glycerol channel from Escherichia coli at 2.2 A resolution
      serves as a basis for the understanding of selective transmembrane substrate
      permeation. In the course of permeation, glycerol molecules diffuse through a
      tripathic channel with their alkyl backbone wedged against a hydrophobic corner,
      such that OH groups become acceptors and donors of hydrogen bonds at the same
      time. The structure of the channel explains the preferential permeability for
      linear carbohydrates and absolute exclusion of ions and charged solutes. Its gene
      duplicated sequence has a structural counterpart in a pseudo two-fold symmetry
      within the monomeric channel protein.

PMID- 11532443
TI  - Neuronal nicotinic receptors: from protein structure to function.
AB  - Neuronal nicotinic acetylcholine receptors are a prototype of ligand-gated
      channels that mediate transmission in the central and peripheral nervous system.
      Structure-function studies performed at the amino acid level are now unraveling
      the determinant residues either for the properties of the ligand-binding domain
      or the ionic pore. In this work we review, in the light of the latest finding,
      the structure-function relationship of these receptors and their implication in
      neurological diseases.

PMID- 11532444
TI  - Insights from the structure of the yeast cytochrome bc1 complex: crystallization
      of membrane proteins with antibody fragments.
AB  - The ubiquinol:cytochrome c oxidoreductase (EC 1.20.2.2, QCR or cytochrome bc1
      complex) is a component of respiratory and photosynthetic electron transfer
      chains in mitochondria and bacteria. The complex transfers electrons from quinol
      to cytochrome c. Electron transfer is coupled to proton translocation across the
      lipid bilayer, thereby generating an electrochemical proton gradient, which
      conserves the free energy of the redox reaction. The yeast complex was
      crystallized with antibody Fv fragments, a promising technique to obtain well
      ordered crystals from membrane proteins. The high-resolution structure of the
      yeast protein reveals details of the catalytic sites of the complex, which are
      important for electron and proton transfer.

PMID- 11532445
TI  - Succinate:quinone oxidoreductases--what can we learn from Wolinella succinogenes
      quinol:fumarate reductase?
AB  - The structure of Wolinella succinogenes quinol:fumarate reductase by X-ray
      crystallography has been determined at 2.2-A resolution [Lancaster et al. (1999),
      Nature 402, 377-385]. Based on the structure of the three protein subunits A, B,
      and C and the arrangement of the six prosthetic groups (a covalently bound FAD,
      three iron-sulphur clusters, and two haem b groups) a pathway of electron
      transfer from the quinol-oxidising dihaem cytochrome b in the membrane to the
      site of fumarate reduction in the hydrophilic subunit A has been proposed. By
      combining the results from site-directed mutagenesis, functional and
      electrochemical characterisation, and X-ray crystallography, a residue was
      identified which is essential for menaquinol oxidation. [Lancaster et al. (2000),
      Proc. Natl. Acad. Sci. USA 97, 13051-13056]. The location of this residue in the
      structure suggests that the coupling of the oxidation of menaquinol to the
      reduction of fumarate in dihaem-containing succinate:quinone oxidoreductases
      could be associated with the generation of a transmembrane electrochemical
      potential. Based on crystallographic analysis of three different crystal forms of
      the enzyme and the results from site-directed mutagenesis, we have derived a
      mechanism of fumarate reduction and succinate oxidation [Lancaster et al. (2001)
      Eur. J. Biochem. 268, 1820-1827], which should be generally relevant throughout
      the superfamily of succinate:quinone oxidoreductases.

PMID- 11532446
TI  - Subunit positioning and transmembrane helix organisation in the core dimer of
      photosystem II.
AB  - Recently 3D structural models of the photosystem II (PSII) core dimer complexes
      of higher plants (spinach) and cyanobacteria (Synechococcus elongatus) have been
      derived by electron [Rhee et al. (1998) Nature 396, 283-286; Hankamer et al.
      (2001) J. Struct. Biol., in press] and X-ray [Zouni et al. (2001) Nature 409, 739
      743] crystallography respectively. The intermediate resolutions of these
      structures do not allow direct identification of side chains and therefore many
      of the individual subunits within the structure are unassigned. Here we review
      the structure of the higher plant PSII core dimer and provide evidence for the
      tentative assignment of the low molecular weight subunits. In so doing we
      highlight the similarities and differences between the higher plant and
      cyanobacterial structures.

PMID- 11532447
TI  - Inter-subunit rotation and elastic power transmission in F0F1-ATPase.
AB  - ATP synthase (F-ATPase) produces ATP at the expense of ion-motive force or vice
      versa. It is composed from two motor/generators, the ATPase (F1) and the ion
      translocator (F0), which both are rotary steppers. They are mechanically coupled
      by 360 degrees rotary motion of subunits against each other. The rotor, subunits
      gamma(epsilon)C10-14, moves against the stator, (alphabeta)3delta(ab2). The
      enzyme copes with symmetry mismatch (C3 versus C10-14) between its two motors,
      and it operates robustly in chimeric constructs or with drastically modified
      subunits. We scrutinized whether an elastic power transmission accounts for these
      properties. We used the curvature of fluorescent actin filaments, attached to the
      rotating c ring, as a spring balance (flexural rigidity of 8.10(-26) N x m2) to
      gauge the angular profile of the output torque at F0 during ATP hydrolysis by F1.
      The large average output torque (56 pN nm) proved the absence of any slip.
      Angular variations of the torque were small, so that the output free energy of
      the loaded enzyme decayed almost linearly over the angular reaction coordinate.
      Considering the three-fold stepping and high activation barrier (>40 kJ/mol) of
      the driving motor (F1) itself, the rather constant output torque seen by F0
      implied a soft elastic power transmission between F1 and F0. It is considered as
      essential, not only for the robust operation of this ubiquitous enzyme under
      symmetry mismatch, but also for a high turnover rate under load of the two
      counteracting and stepping motors/generators.

PMID- 11532448
TI  - Solid-state NMR investigations of interaction contributions that determine the
      alignment of helical polypeptides in biological membranes.
AB  - Helical peptides reconstituted into oriented phospholipid bilayers were studied
      by proton-decoupled 15N solid-state NMR spectroscopy. Whereas hydrophobic channel
      peptides, such as the N-terminal region of Vpu of HIV-1, adopt transmembrane
      orientations, amphipathic peptide antibiotics are oriented parallel to the
      bilayer surface. The interaction contributions that determine the alignment of
      helical peptides in lipid membranes were analysed using model sequences, and
      peptides that change their topology in a pH-dependent manner have been designed.
      The energy contributions of histidines, lysines, leucines and alanines as well as
      the alignment of peptides and phospholipids under conditions of hydrophobic
      mismatch have been investigated in considerable detail.

PMID- 11532449
TI  - Two-dimensional crystals: a powerful approach to assess structure, function and
      dynamics of membrane proteins.
AB  - Electron crystallography and atomic force microscopy allow the study of two
      dimensional membrane protein crystals. While electron crystallography provides
      atomic scale three-dimensional density maps, atomic force microscopy gives
      insight into the surface structure and dynamics at sub-nanometer resolution.
      Importantly, the membrane protein studied is in its native environment and its
      function can be assessed directly. The approach allows both the atomic structure
      of the membrane protein and the dynamics of its surface to be analyzed. In this
      way, the function-related conformational changes can be assessed, thus providing
      a detailed insight on the molecular mechanisms of essential biological processes.

PMID- 11532450
TI  - Solution NMR studies of the integral membrane proteins OmpX and OmpA from
      Escherichia coli.
AB  - Membrane proteins are usually solubilized in polar solvents by incorporation into
      micelles. Even for small membrane proteins these mixed micelles have rather large
      molecular masses, typically beyond 50000 Da. The NMR technique TROSY (transverse
      relaxation-optimized spectroscopy) has been developed for studies of structures
      of this size in solution. In this paper, strategies for the use of TROSY-based
      NMR experiments with membrane proteins are discussed and illustrated with results
      obtained with the Escherichia coli integral membrane proteins OmpX and OmpA in
      mixed micelles with the detergent dihexanoylphosphatidylcholine (DHPC). For OmpX,
      complete sequence-specific NMR assignments have been obtained for the polypeptide
      backbone. The 13C chemical shifts and nuclear Overhauser effect data then
      resulted in the identification of the regular secondary structure elements of
      OmpX/DHPC in solution, and in the collection of an input of conformational
      constraints for the computation of the global fold of the protein. For OmpA, the
      NMR assignments are so far limited to about 80% of the polypeptide chain,
      indicating different dynamic properties of the reconstituted OmpA beta-barrel
      from those of OmpX. Overall, the present data demonstrate that relaxation
      optimized NMR techniques open novel avenues for studies of structure, function
      and dynamics of integral membrane proteins.

PMID- 11532451
TI  - Molecular mechanism for the crystallization of bacteriorhodopsin in lipidic cubic
      phases.
AB  - Crystals of transmembrane proteins may be grown from detergent solutions or in a
      matrix of membranous lipid bilayers existing in a liquid crystalline state and
      forming a cubic phase (in cubo). While crystallization in micellar solutions
      appears analogous to that for soluble proteins, crystallization in lipidic
      matrices is poorly understood. As this method was shown to be applicable to
      several membrane proteins, understanding its mechanism will facilitate a rational
      design of crystallization, minimizing the laborious screening of a large number
      of parameters. Using polarization microscopy and low-angle X-ray diffraction,
      experimental evidence is provided to support a mechanistic model for the in cubo
      crystallization of bacteriorhodopsin in a lipid matrix. Membrane proteins are
      thought to reside in curved lipid bilayers, to diffuse into patches of lower
      curvature and to incorporate into lattices which associate to form highly ordered
      three-dimensional crystals. Critical testing of this model is necessary to
      generalize it to other membrane proteins.

PMID- 11532452
TI  - Two-dimensional crystallization of membrane proteins: the lipid layer strategy.
AB  - Due to the difficulty to crystallize membrane proteins, there is a considerable
      interest to intensify research topics aimed at developing new methods of
      crystallization. In this context, the lipid layer crystallization at the
      air/water interface, used so far for soluble proteins, has been recently adapted
      successfully to produce two-dimensional (2D) crystals of membrane proteins,
      amenable to structural analysis by electron crystallography. Besides to represent
      a new alternative strategy, this approach gains the advantage to decrease
      significantly the amount of material needed in incubation trials, thus opening
      the field of crystallization to those membrane proteins difficult to surexpress
      and/or purify. The systematic studies that have been performed on different
      classes of membrane proteins are reviewed and the physico-chemical processes that
      lead to the production of 2D crystals are addressed. The different drawbacks,
      advantages and perspectives of this new strategy for providing structural
      information on membrane proteins are discussed.

PMID- 11532453
TI  - Imaging domains in model membranes with atomic force microscopy.
AB  - Lateral segregation in biomembranes can lead to the formation of biologically
      functional domains. This paper reviews atomic force microscopy studies on domain
      formation in model membranes, with special emphasis on transbilayer asymmetry,
      and on lateral domains induced by lipid-lipid interactions or by peptide-lipid
      interactions.

PMID- 11532454
TI  - Large-scale purification of functional recombinant human aquaporin-2.
AB  - The homotetrameric aquaporin-2 (AQP2) water channel is essential for the
      concentration of urine and of critical importance in diseases with water
      dysregulation, such as nephrogenic diabetes insipidus, congestive heart failure,
      liver cirrhosis and pre-eclampsia. The structure of human AQP2 is a prerequisite
      for understanding its function and for designing specific blockers. To obtain
      sufficient amounts of AQP2 for structural analyses, we have expressed recombinant
      his-tagged human AQP2 (HT-AQP2) in the baculovirus/insect cell system. Using the
      protocols outlined in this study, 0.5 mg of pure HT-AQP2 could be obtained per
      liter of bioreactor culture. HT-AQP2 had retained its homotetrameric structure
      and exhibited a single channel water permeability of 0.93+/-0.03x10(-13) cm3/s,
      similar to that of other AQPs. Thus, the baculovirus/insect cell system allows
      large-scale expression of functional recombinant human AQP2 that is suitable for
      structural studies.

PMID- 11532455
TI  - A refined structure of human aquaporin-1.
AB  - A refined structure of the human water channel aquaporin-1 is presented. The
      model rests on the high resolution X-ray structure of the homologous bacterial
      glycerol transporter GlpF, electron crystallographic data at 3.8 A resolution and
      a multiple sequence alignment of the aquaporin superfamily. The crystallographic
      R and free R values (36.7% and 37.8%) for the refined structure are significantly
      lower than for previous models. Improved geometry and enhanced stability in
      molecular dynamics simulations demonstrate a significant improvement of the
      aquaporin-1 structure. Comparison with previous aquaporin-1 models shows
      significant differences, not only in the loop regions, but also in the core of
      the water channel.

PMID- 11532456
TI  - Molecular dynamics study of aquaporin-1 water channel in a lipid bilayer.
AB  - The aquaporin-1 water channel was modeled in a palmitoyl-oleoyl-phosphatidyl
      choline lipid bilayer, by means of molecular dynamics simulations. Interaction of
      the protein with the membrane and inter-monomer interactions were analyzed.
      Structural features of the channel important for its biological function,
      including the Asn-Pro-Ala (NPA) motifs, and the diffusion of water molecules into
      the channels, were investigated. Simulations revealed the formation of single
      file water inside the channels for certain relative positions of the NPA motifs.

PMID- 11532457
TI  - ATP synthase: constrained stoichiometry of the transmembrane rotor.
AB  - Recent structural data suggest that the number of identical subunits (c or III)
      assembled into the cation-powered rotor of F1F0 ATP synthase depends on the
      biological origin. Atomic force microscopy allowed individual subunits of the
      cylindrical transmembrane rotors from spinach chloroplast and from Ilyobacter
      tartaricus ATP synthase to be directly visualized in their native-like
      environment. Occasionally, individual rotors exhibit structural gaps of the size
      of one or more subunits. Complete rotors and arch-shaped fragments of incomplete
      rotors revealed the same diameter within one ATP synthase species. These results
      suggest the rotor diameter and stoichiometry to be determined by the shape of the
      subunits and their nearest neighbor interactions.

PMID- 11532460
TI  - Funding in vitro fertilization treatment for persistent subfertility: the pain
      and the politics.
AB  - OBJECTIVE: To consider the arguments for and against funding for in vitro
      fertilization (IVF) and to explore potential avenues for policy change. DESIGN:
      Narrative literature review, policy analysis. SETTING: University Department of
      Obstetrics and Gynecology. PATIENT(S): Sub-fertile women and men.
      INTERVENTION(S): Fertility treatments, in particular IVF. RESULT(S): The two main
      arguments used against funding for IVF are that [1] subfertility is a social, not
      a medical problem, and therefore its treatment is not medically indicated or
      necessary, and [2] the clinical effectiveness of IVF is unproven. These and other
      major arguments are critiqued. CONCLUSION(S): Dismissing IVF as medically
      unnecessary seems premature because medical necessity has not been operationally
      defined. Demonstrating IVF effectiveness through a randomized trial has not been
      done but is feasible: a multicenter trial is currently underway in Canada.
      Dealing with the concern that subfertility treatment challenges the role of women
      in society, as well as with questions of cost-effectiveness, are more difficult
      challenges that deserve further debate. The potential for unethical uses and
      broader social implications of IVF add to its dubious status and provide a
      convenient rationale for refusing to pay. However, none of these concerns is
      unique to IVF: many currently covered health services are susceptible to the same
      criticisms. For all services, judgments of eligibility for coverage should be
      consistent and transparent and should explicitly separate the issues of cost from
      other factors.

PMID- 11532458
TI  - Features of V-ATPases that distinguish them from F-ATPases.
AB  - The general structure of F- and V-ATPases is quite similar and they may share a
      common mechanism of action that involves mechanochemical energy transduction.
      Both holoenzymes are composed of catalytic sectors, F1 and V1 respectively, and
      membrane sectors, F(o) and V(o) respectively. Although we assume that a similar
      mechanism underlies ATP-dependent proton pumping by F- and V-ATPases in
      eukaryotic cells, the latter cannot catalyze pmf-driven ATP synthesis. The loss
      of this ability is probably due to a proton slip that is a consequence of
      alterations in its membrane sector. The major events include gene duplication of
      the proteolipids and the presence of three distinct proteolipids in each complex.

PMID- 11532461
TI  - Gonadotropin-releasing hormone antagonists instead of agonists: a change for the
      better?

PMID- 11532462
TI  - Mammographic density changes during different postmenopausal hormone replacement
      therapies.
AB  - OBJECTIVE: To determine the degree of change in mammographic breast densities
      during different types of postmenopausal hormone replacement therapies. DESIGN: A
      retrospective study. SETTING: Ege University Hospital. PATIENT(S): The
      mammographies of 216 women on various postmenopausal hormone replacement
      therapies were evaluated. INTERVENTION(S): Estrogen alone (n = 76) or estrogen in
      cyclic (n = 44) or continuous (n = 61) combination with progestin or tibolone
      only (n = 35) replacement therapies were used. Mammographic density was
      quantified according to the Wolfe classification in patients with different
      hormone replacement regimens. MAIN OUTCOME MEASURE(S): Mammographic density
      changes were interpreted. RESULT(S): An increase in mammographic density was much
      more common among women receiving continuous combination hormone replacement
      therapy 31.1% (19 of 61) than among those receiving estrogen-only 3.9% (3 of 76)
      treatment. There were no significant mammographic breast density changes among
      women receiving cyclic continuous combination hormone replacement therapy or
      tibolone-only treatment. The increase in density was apparent already at first
      visit after the start of hormone replacement therapy. In continuous combined
      postmenopausal hormone replacement therapy with norethisterone acetate, the
      increase in mammographic density was 34.1% (15 of 44), followed by
      medroxyprogesterone acetate 23.5% (4 of 17). CONCLUSION(S): Our findings show
      that mammographic breast density changes related to postmenopausal hormone
      replacement therapy are dependent on the selected hormone regimen. The continuous
      administration of the progestin component of the combined-hormone replacement
      therapy seems to effect the breast density most.

PMID- 11532463
TI  - Effects of a short-term suspension of hormone replacement therapy on mammographic
      density.
AB  - OBJECTIVE: To evaluate the effects of hormone replacement therapy (HRT) and of a
      short-term suspension of HRT on mammographic density. DESIGN: Prospective
      clinical study. SETTING: Outpatient menopausal clinic of the Second University of
      Naples. PATIENT(S): Ninety-seven healthy postmenopausal women. INTERVENTION(S):
      Thirty-nine menopausal women with intact uterus (group A) were treated with
      continuous transdermal E(2) plus acetate nomegestrolo sequentially added, 37
      women in surgical menopause (group B) were treated with transdermal E(2)
      continuously administered, and 21 menopausal women did not receive any medication
      (group C). At the entry and after 12 months, a mammography was performed without
      suspension of HRT (group A1: 19 women; group B1: 19 women) or after a short-term
      suspension (group A2: 20 women; group B2: 18 women). MAIN OUTCOME MEASURE(S):
      Mammographic density evaluated according to a quantitative method. RESULT(S): At
      the second mammography, seven patients in group A1, four patients in group B1,
      and one patient in both groups A2 and B2 showed an increase in mammographic
      density, whereas no mammographic density increase was observed in patients in
      group C. A statistically significant difference in the mammographic density
      increase was found between group A1 and group A2; no difference was found between
      group B1 and B2. CONCLUSION(S): Suspension of HRT for about 3 weeks may reverse
      mammographic density increase associated with its use.

PMID- 11532464
TI  - Are changes in sexual functioning during midlife due to aging or menopause?
AB  - OBJECTIVE: To determine whether changes in women's sexual functioning during
      midlife are due to aging or menopause. DESIGN: Prospective, observational study.
      SETTING: Population-based sample assessed in own homes. PATIENT(S): Four hundred
      thirty-eight Australian-born women aged 45-55 years and still menstruating at
      baseline. One hundred ninety-seven were studied for effects of the natural
      menopausal transition. Control group A (n = 44) remained premenopausal or early
      perimenopausal for 7 years. Control group B (n = 42) remained postmenopausal over
      5 years. INTERVENTION(S): Nil; questionnaires and blood sampling annually. MAIN
      OUTCOME MEASURE(S): Shortened version of the Personal Experiences Questionnaire.
      RESULT(S): By the late perimenopause, there was a significant decline in the
      factors we had derived of sexual responsivity and total score, and there was an
      increase in the partner's problems factor. By the postmenopausal phase, there was
      a further decline in the factors sexual responsivity, frequency of sexual
      activities, libido, and in the total score, and a significant increase in vaginal
      dyspareunia and partner's problems. Sexual responsivity significantly declined in
      both control groups. CONCLUSION(S): Sexual responsivity is adversely affected by
      both aging and the menopausal transition. Other domains of female sexual
      functioning were significantly adversely affected when the women became
      postmenopausal. The relationship with the partner and his ability to perform
      sexually is adversely affected by the menopausal transition.

PMID- 11532466
TI  - Forearm bone density in long-term users of oral combined contraceptives and depot
      medroxyprogesterone acetate.
AB  - OBJECTIVE: To compare the bone mineral density of users of combined oral
      contraceptives (OC) or depot medroxyprogesterone acetate (depot-MPA) with women
      who have never used a hormonal contraceptive method. DESIGN: Cross-sectional
      study. SETTING: Academic tertiary-care hospital. PATIENT(S): A total of 189
      women, aged 30 to 34 years old, were allocated to three groups: 63 who had used
      OC for at least 2 years; 63 who had used depot-MPA for at least 2 years; and 63
      control women who had never used hormonal contraceptives. INTERVENTION(S): Each
      woman's bone mineral density (BMD) was evaluated at the distal and ultradistal
      section of the radius of the nondominant forearm by the use of single x-ray
      absorptiometry. MAIN OUTCOME MEASURE(S): We obtained BMD measurements for each
      participant. RESULT(S): Independent of the period of use and the section of the
      forearm studied, we found no difference in BMD for OC or depot-MPA users when
      compared to women who had never used hormonal contraceptive methods. In addition,
      BMD was similar between OC users and depot-MPA users. The multiple linear
      regression analysis showed that the variables associated with BMD were weight,
      number of pregnancies, and the woman's occupation. CONCLUSION(S): Women aged 30
      to 34 years who have used OC or depot-MPA have similar BMD as control women.
      These findings suggest that the use of OC or depot-MPA does not affect the BMD of
      women in this age group.

PMID- 11532465
TI  - A randomized, controlled trial of a low-dose contraceptive containing 20 microg
      of ethinyl estradiol and 100 microg of levonorgestrel for acne treatment.
AB  - OBJECTIVE: To evaluate the efficacy of a low-dose oral contraceptive (OC)
      containing 100 microg of levonorgestrel (LNG) and 20 microg of ethinyl estradiol
      (EE) compared with placebo for the treatment of moderate acne. DESIGN:
      Multicenter, randomized, double-blind, placebo-controlled clinical trial.
      SETTING: Outpatient dermatology clinics. PATIENT(S): Women (> or =14 years old; n
      = 350) with normal menstrual cycles and moderate acne were randomized to receive
      LNG/EE or placebo for six cycles. INTERVENTION(S): Twenty microg of EE and 100
      microg of LNG. MAIN OUTCOME MEASURE(S): Acne lesion counts and clinician global
      assessment were performed at baseline and at each cycle. Patient self-assessment
      was carried out at baseline and at cycles 4 and 6; blood pressure and weight were
      measured at baseline and at cycles 1, 3, and 6. RESULT(S): Inflammatory,
      noninflammatory, and total lesion counts at cycle 6 with LNG/EE were
      significantly lower compared to placebo. Patients in the LNG/EE group also had
      significantly better clinician global and patient self-assessment scores than
      those in the placebo group at cycle. Changes in weight from baseline were similar
      between patients in the LNG/EE and placebo groups at all measured time points.
      CONCLUSION(S): This double-blind, placebo-controlled study demonstrates that a
      low-dose OC containing 20 microg of EE and 100 microg of LNG is an effective and
      safe treatment for moderate acne.

PMID- 11532467
TI  - Endometrial expression of glycodelin in women with levonorgestrel-releasing
      subdermal implants.
AB  - OBJECTIVE: To determine whether subdermal levonorgestrel implants induce
      endometrial expression of glycodelin. DESIGN: Cross-sectional, blinded study.
      SETTING: University clinic. PATIENT(S): One hundred and eight women with
      subdermal implants and 19 postmenopausal women. INTERVENTION(S): Endometrial
      biopsies, curettages, and hysterectomies. MAIN OUTCOME MEASURE(S): Endometrial
      glycodelin expression was examined through immunohistochemistry, in situ
      hybridization, and morphologic endometrial dating. RESULT(S): Overall, 80% of the
      endometrial specimens obtained from women with subdermal levonorgestrel implants
      stained positive for glycodelin. Endometrial morphology of these women showed
      proliferative (71%), inactive/weakly proliferative (19%), menstrual or
      regenerating (6.5%), and other patterns (2.8%). Of these, 79%, 71%, 100%, and
      100% were glycodelin positive, respectively. Nineteen specimens were obtained
      during the midcycle when glycodelin is not normally expressed: of these, 89%
      stained positive for glycodelin. Implant-related amenorrhea was associated with
      endometrial glycodelin expression in 58% of the women, whereas the endometrium
      specimens obtained from women with postmenopausal hypoestrogenic amenorrhea
      contained no detectable glycodelin. CONCLUSION(S): Subdermal levonorgestrel
      implant use is often associated with endometrial expression of glycodelin.
      Because glycodelin has been shown to inhibit sperm-egg binding, the induction of
      glycodelin may contribute to the contraceptive activity of the implant.

PMID- 11532468
TI  - Sperm chromosome abnormalities in men with severe male factor infertility who are
      undergoing in vitro fertilization with intracytoplasmic sperm injection.
AB  - OBJECTIVE: To investigate the potential paternal contribution to the risk of
      fetal chromosomal anomalies after intracytoplasmic sperm injection (ICSI).
      DESIGN: Spermatozoa isolated from testicular tissue and ejaculated specimens of
      consenting patients undergoing testicular biopsy and ICSI were analyzed for
      chromosomes X, Y, and 18 by FISH. SETTING: Assisted reproductive technology
      program. PATIENT(S): Consenting patients undergoing testicular biopsy and ICSI,
      severe oligozoospermic patients, and normal fertile donors. INTERVENTION(S):
      None. MAIN OUTCOME MEASURE(S): The rate of chromosome abnormalities in testicular
      sperm with regard to the type of azoospermia and ejaculated sperm compared to
      healthy men. RESULT(S): The mean serum levels of FSH in the groups with
      nonobstructive azoospermia (n = 9), obstructive azoospermia (n = 10), severe
      oligozoospermia (n = 9), and the normal donors (n = 6) were 17.5 +/- 8.2 (P<.05),
      3.5 +/- 2.6, 14.6 +/- 3.5 (P<.05), and 3.1 +/- 0.4 IU/mL, respectively. The
      corresponding rates of sperm chromosome abnormalities among these groups were
      19.6% (P<.001), 8.2% (P<.001), 13.0% (P<.001), and 1.6%, respectively. The
      corresponding rates of disomy among these groups were 7.8% (12 of 153
      spermatozoa), 4.9% (18 of 367), 6.2% (109 of 1,751), and 1% (5 of 500
      spermatozoa), respectively. Errors in chromosomes X and Y were significantly more
      common than in chromosome 18. CONCLUSION(S): The present findings demonstrate a
      linkage between gonadal failure (high serum FSH levels) and the occurrence of
      sperm chromosome aneuploidies. Our findings may explain the increased incidence
      of sex chromosome abnormalities found after IVF in the severe male factor patient
      population. Genetic screening during pregnancy or before embryo replacement
      should be considered carefully.

PMID- 11532469
TI  - Influence of a short or long abstinence period on semen parameters in the
      ejaculate of patients with nonobstructive azoospermia.
AB  - OBJECTIVE: To compare the effect of a short (4 days) or a long (14 days)
      abstinence period on sperm retrieval by extended sperm preparation in patients
      with nonobstructive azoospermia scheduled for testicular biopsy and
      intracytoplasmic sperm injection (ICSI). DESIGN: A prospective case control
      study. SETTING: Male infertility clinic in a university hospital. PATIENT(S):
      Fifty male patients with nonobstructive azoospermia, scheduled for testicular
      biopsy for ICSI. INTERVENTION(S): Diagnosis of nonobstructive azoospermia and a
      thorough microscopic search for sperm cells (extended sperm preparation). MAIN
      OUTCOME MEASURE(S): The number of sperm cells collected, sperm motility, and
      total motile sperm count after short and long abstinence periods. RESULT(S):
      There was a significant difference between long and short abstinence with an
      increase in sperm count (log-to-log transformed analysis of variance P<.025) and
      total motile sperm (P<.025 analysis of variance, P<.02 paired Student's t-test)
      in the former group, but no significant change in sperm motility (Wilcoxon and
      paired Student's t-test). In 18 patients, sperm concentration and sperm motility
      were similar in a second collection, done after the same abstinence period,
      compared with the same parameters in the first sample. When at least 10 motile
      sperm were defined as the cutoff number, allowing ICSI without testicular biopsy,
      no significant differences were found between the two abstinence periods. No
      clinical or laboratory male characteristic could predict the detection of 10
      motile sperm by extended sperm preparation either after a short or a long
      abstinence period. CONCLUSION(S): Sperm count and total motile sperm were
      increased after a long abstinence period, with no change in sperm motility. No
      additional advantages were conferred by long abstinence as opposed to short
      abstinence when 10 motile sperm were defined as the cutoff number for ICSI. The
      recommended period of abstinence for extended sperm preparation and ICSI, whether
      short or long, should be individualized for each patient.

PMID- 11532470
TI  - Y-chromosome microdeletion and phenotype in cytogenetically normal men with
      idiopathic azoospermia.
AB  - OBJECTIVE: To determine the prevalence of microdeletions of the long arm of
      chromosome Y within the AZFa, AZFb, and AZFc subregions in patients with
      idiopathic azoospermia, and then correlate the microdeletions with clinical
      phenotypes to determine the most important subregion for screening. DESIGN:
      Controlled clinical study. SETTING: Male infertility clinic, Kobe University
      Hospital. PATIENT(S): Among 89 consecutive azoospermic patients, those whose
      infertility was related to known hereditary, endocrine, or obstructive causes or
      a cytogenetic abnormality were excluded; 54 remaining patients were studied using
      a polymerase chain reaction (PCR). Of these patients, 33 had Sertoli cell only
      syndrome, 10 had maturation arrest, and 11 had hypospermatogenesis.
      INTERVENTION(S): Blood and semen samples and testicular biopsies were obtained
      from all of the participants. MAIN OUTCOME MEASURE(S): We performed semen
      analysis, polymerase chain amplification of 28 DNA loci on the long arm of the Y
      chromosome involving the DAZ (deleted in azoospermia), and measured the plasma
      FSH, LH, testosterone, prolactin, and estradiol levels. RESULT(S): Microdeletions
      were detected in 14 of the 54 patients (nine with Sertoli cell only, three with
      maturation arrest, and two with hypospermatogenesis). Most microdeletions
      involved AZFb or AZFc. Patients with hypospermatogenesis or maturation arrest
      showed deletion only in AZFc. The DAZ gene was deleted in four patients with
      Sertoli cell only and one patient with maturation arrest. The RBM gene was
      deleted in two patients with Sertoli cell only who had particularly large
      deletions, but in no patients with arrest or hypospermatogenesis. CONCLUSION(S):
      Cytogenetically azoospermic patients should be examined for microdeletions before
      undertaking assisted reproduction. AZFc may be the most important subregion to
      screen. In addition, intact AZFa and AZFb subregions may be important for the
      presence of germ cells.

PMID- 11532471
TI  - The concentration of nitrite in seminal plasma does not correlate with sperm
      concentration, sperm motility, leukocytospermia, or sperm culture.
AB  - OBJECTIVE: To correlate the concentration of nitrite (the stable metabolite of
      nitric oxide) in seminal plasma with sperm number and motility, leukocytospermia,
      and sperm culture. DESIGN: Prospective study. SETTING: Academic research
      institution. PATIENT(S): Seventy normozoospermic or dyspermic men enrolled in an
      artificial insemination/in vitro fertilization program. INTERVENTION(S): Semen
      samples (n = 70) were checked for sperm concentration, total sperm count, sperm
      motility, seminal leukocyte concentration, and sperm culture; similarly, the
      concentration of nitrite in seminal plasma was measured by Griess reaction. MAIN
      OUTCOME MEASURE(S): Measurement of nitrite concentration in seminal plasma and
      its correlation with sperm concentration, total sperm count, sperm motility,
      leukocytospermia, and sperm culture. RESULT(S): The concentration of nitrite in
      seminal plasma does not correlate with sperm concentration, total sperm count, or
      with the proportion of immotile or rapid-forward motile spermatozoa. Moreover,
      the concentration of nitrite in seminal plasma is not significantly increased
      when sperm culture is positive, nor does it correlate with leukocyte
      concentration in semen. CONCLUSION(S): Our results do not support the hypothesis
      that in vivo nitric oxide synthesis affects sperm function; alternatively, our
      results could suggest that nitrite in the seminal plasma is not a sensitive
      marker of in vivo nitric oxide synthesis.

PMID- 11532472
TI  - Laurdan fluorescence: a simple method to evaluate sperm plasma membrane
      alterations.
AB  - OBJECTIVE: To determine, by a simple fluorescence method, sperm plasma membrane
      alterations related with changes of lipid bilayer that, together with routine
      semen analysis, could help to elucidate the causes of the unexplained male
      infertility problems. DESIGN: Pilot study. SETTING: Andrology laboratory and
      biochemistry institute, medical school. PATIENT(S): Men whose semen was studied
      for infertility problems. INTERVENTIONS(S): No therapeutic intervention was
      performed on patients. MAIN OUTCOME MEASURE(S): Presence of spermatozoa plasma
      membrane alterations evidenced by evaluation of Laurdan fluorescence Generalized
      Polarization (GP) and reported as a function of increasing cell concentration,
      spermatozoa total motility, linear speed, and vitality. RESULT(S): Reporting GP
      values as a function of increasing sperm cell concentration, it is evident that
      the samples are distributed in two distinct areas: at >32 x 10(6) cells per
      milliliter, mean GP value was 0.303 +/- 0.015, whereas for lower sperm cell
      concentrations, the mean GP was 0.365 +/- 0.026 (P<.001). These data indicate
      that the spermatozoa plasma membranes are characterized by liquid-crystalline
      phases with different ordering degree and polarity and that about 50% of samples
      with normal semen characteristics (> or =20 x 10(6) cells per milliliter) show
      high GP values. CONCLUSION(S): Laurdan fluorescence can be used as a simple
      method to evaluate spermatozoa plasma membrane alterations, particularly in a
      group of infertile men presenting normal semen parameters. In these samples,
      Laurdan could be used as a simple tool for infertility assessment. In fact, it is
      known that compositional and physicochemical alterations of bilayer features can
      be important for the fertilizing ability of spermatozoa because they are
      necessary for a proper physiological membrane activity.

PMID- 11532473
TI  - Increased 6-sulfatoxymelatonin excretion in women with polycystic ovary syndrome.
AB  - OBJECTIVE: To determine melatonin production in hyperandrogenic women. DESIGN:
      Controlled prospective study. SETTING: Outpatients in an academic medical center.
      PATIENT(S): Twenty-two women with polycystic ovary syndrome (PCOS), 20 women with
      idiopathic hirsutism, and 15 age-matched individuals who had similar body mass
      indexes as controls. INTERVENTION(S): Fasting blood samples and 24-hour urinary
      samples were obtained from all participants. MAIN OUTCOME MEASURE(S): All
      participants provided serum samples for the measurement of LH, FSH, testosterone,
      E(2), DHEAS, 17 alpha-hydroxyprogesterone (17-OHP), and insulin levels, as well
      as urinary 6-sulfatoxymelatonin (aMT6s). RESULT(S): Women with PCOS had higher
      aMT6s, testosterone, LH/FSH ratio, and insulin values than either women with
      idiopathic hirsutism or control women. Testosterone inversely correlated with
      aMT6s in PCOS. Regression analysis revealed that only testosterone was an
      important determinant of aMT6s in PCOS. CONCLUSION(S): Women with PCOS have
      increased melatonin production.

PMID- 11532474
TI  - Diastolic dysfunction and increased serum homocysteine concentrations may
      contribute to increased cardiovascular risk in patients with polycystic ovary
      syndrome.
AB  - OBJECTIVE: To assess cardiac flow parameters in patients with polycystic ovary
      syndrome (PCOS). DESIGN: A prospective case-control study. SETTING: University
      based hospital. PATIENT(S): Thirty consecutive patients with PCOS were enrolled.
      Thirty women with regular menstrual cycles served as the controls.
      INTERVENTION(S): Systolic and diastolic function parameters were assessed by
      standard two-dimensional and M-mode echocardiography. Insulin sensitivity was
      evaluated by a standard 75-g oral glucose tolerance test and area-under-curve
      insulin analysis. Serum hormones, lipid profile, homocysteine, vitamin B(12),
      folate, fibrinogen, uric acid, and plasminogen activator inhibitor-I
      concentrations were measured. MAIN OUTCOME MEASURE(S): Systolic and diastolic
      function parameters, insulin sensitivity and serum homocysteine levels.
      RESULT(S): The mean serum homocysteine and uric acid concentrations were
      significantly higher in the PCOS group. Patients with PCOS had significant
      hyperinsulinemia. All systolic function parameters were comparable between the
      two groups. However, patients with PCOS had significantly lower peak mitral flow
      velocity in early diastole and significantly lower ratio between the early and
      late peak mitral flow velocities and also had significantly longer isovolumic
      relaxation time, reflecting a trend for nonrestrictive-type diastolic
      dysfunction. The area-under-curve insulin correlated positively with peak mitral
      flow velocity in late diastole (r = 0.375). The mean cholesterol/high-density
      lipoprotein ratio correlated negatively with mean mitral flow velocity in early
      diastole (E) peak (r = -0.474). The mean fasting insulin level correlated
      negatively with mean E/A ratio (r = -0.387). CONCLUSION(S): Diastolic dysfunction
      and increased serum homocysteine concentrations may contribute to increased
      cardiovascular disease risk in patients with PCOS.

PMID- 11532476
TI  - Stress and marital satisfaction among women before and after their first cycle of
      in vitro fertilization and intracytoplasmic sperm injection.
AB  - OBJECTIVE: To determine differences in emotional status (anxiety and depression)
      and marital satisfaction in pregnant and nonpregnant women before and after their
      first cycle of IVF and intracytoplasmic sperm injection (ICSI). DESIGN: Repeated
      measurement. SETTING: Fertility department at a university and a regional
      hospital. PATIENT(S): Women entering their first treatment cycle of IVF or ICSI.
      INTERVENTION(S): Questionnaires on psychological factors were administered 3 to
      12 days before the start of their first treatment cycle and repeated 3 weeks
      after the pregnancy test. MAIN OUTCOME MEASURE(S): State anxiety, depression,
      mood, and marital satisfaction. RESULT(S): At pretreatment, the women who became
      pregnant showed lower levels of depression than those who did not. Higher levels
      of depression in the pregnant women after the first cycle were due to higher
      scores on vital aspects of depression, related to signs of early pregnancy.
      Higher levels of depression in the nonpregnant women were due to a higher score
      on cognitive aspects of depression. CONCLUSION(S): Differences in emotional
      status between pregnant and nonpregnant women were present before treatment and
      became more apparent after the first IVF and ICSI cycle. There were no
      differences in emotional status between the women who underwent IVF and those who
      underwent ICSI.

PMID- 11532475
TI  - Metformin directly inhibits androgen production in human thecal cells.
AB  - OBJECTIVE: To examine the direct effect of metformin on thecal cell androgen
      production. SETTING: Basic science research laboratory, University of Texas
      Southwestern, Dallas, Texas. INTERVENTION(S): Human ovarian theca-like tumor
      cells were treated with various concentrations of metformin in the presence and
      absence of forskolin for 48 hours. MAIN OUTCOME MEASURE(S): Media were collected,
      and radioimmunoassay (RIA) for progesterone, 17 alpha-hydroxyprogesterone
      (17OHP), androstenedione, and testosterone was performed. The effect of metformin
      on the expression of various enzymes involved in theca cell steroidogenesis was
      examined. RESULT(S): Metformin (50 microM and 200 microM) significantly inhibited
      androstenedione production from both forskolin-stimulated and unstimulated theca
      cells. Testosterone production was also significantly inhibited in forskolin
      treated cells in the presence of 200 microM of metformin-treated compared with
      forskolin-only-treated cells. Western blot analysis revealed that metformin
      significantly inhibited the expression of steroidogenic acute regulatory (StAR)
      protein and 17 alpha-hydroxylase (CYP17) expression in cells stimulated with
      forskolin compared with forskolin treatment alone. There was no significant
      change in either 3beta-hydroxysteroid dehydrogenase (3 beta HSD) or cholesterol
      side-chain cleavage (CYP11A1) protein expression. Northern analysis revealed a
      significant decrease in the expression of CYP17 mRNA in forskolin-stimulated
      cells treated with metformin (200 microM) compared with forskolin-only-treated
      cells, however, there was no significant change in steroidogenic acute regulatory
      protein mRNA expression. CONCLUSION(S): Our results suggest that metformin may
      have a direct effect on thecal cells' androgen production.

PMID- 11532477
TI  - A prospective randomized comparison of routine buserelin acetate and a decreasing
      dosage of nafarelin acetate with a low-dose gonadotropin-releasing hormone
      agonist protocol for in vitro fertilization and intracytoplasmic sperm injection.
AB  - OBJECTIVE: To compare the efficacy of a draw-back nafarelin acetate protocol with
      routine buserelin acetate administration for in vitro fertilization (IVF) and
      intracytoplasmic sperm injection (ICSI). DESIGN: Prospective clinical study.
      SETTING: Mie University School of Medicine, Tsu, Mie, Japan. PATIENT(S): One
      hundred sixty-nine women treated with IVF and 183 women treated with ICSI.
      INTERVENTION(S): Nafarelin acetate and buserelin acetate in ovarian
      hyperstimulation in IVF and ICSI were administered. MAIN OUTCOME MEASURE(S): The
      concentrations of estradiol (E(2)), FSH, LH, gonadotropin dosages; the number of
      oocytes retrieved, oocytes fertilized, and embryos; and pregnancy rates.
      RESULT(S): A prospective study was conducted with 44 cycles for 34 couples with
      nafarelin acetate (group 1) and 47 cycles for 40 couples with buserelin acetate
      (group 2) with a long IVF protocol; 68 cycles for 46 couples with nafarelin
      acetate (group 3) and 56 cycles for 39 couples with buserelin acetate (group 4)
      with a short IVF protocol; 39 cycles for 32 couples with nafarelin acetate (group
      5) and 50 cycles for 30 couples with buserelin acetate (group 6) with a long ICSI
      protocol; and 87 cycles for 60 couples with nafarelin acetate (group 7) and 81
      cycles for 61 couples with buserelin acetate (group 8) with a short ICSI
      protocol. Patients were randomized to receive either full-dose nafarelin acetate
      (200 microg b.i.d.) treatment for 7 days followed by half-dose nafarelin acetate
      (200 microg daily) or buserelin acetate (300 microg t.i.d.). There were no
      statistically significant differences in baseline concentrations of E(2) and FSH,
      concentrations of E(2), P4, FSH, LH on hCG administration, gonadotropin dosage,
      the number of oocytes retrieved and embryos transferred, or pregnancy rates
      between groups 1 and 2, groups 3 and 4, groups 5 and 6, and groups 7 and 8.
      CONCLUSION(S): Full-dose nafarelin acetate treatment for 7 days followed by half
      dose nafarelin acetate ("draw-back" protocol) is an effective new protocol for
      IVF and ICSI.

PMID- 11532478
TI  - Dramatic declines in implantation and pregnancy rates in patients who undergo
      repeated cycles of in vitro fertilization with blastocyst transfer after one or
      more failed attempts.
AB  - OBJECTIVE: To compare the outcome of second and third cycles of in vitro
      fertilization with blastocyst transfer to the outcome of first attempts at IVF
      with blastocyst transfer. DESIGN: Retrospective study. SETTING: Private ART
      center. PATIENT(S): Three hundred and four patients undergoing treatment with in
      vitro fertilization with blastocyst transfer, 87 of which underwent at least one
      cycle of re-treatment after failing to achieve pregnancy in their first cycle.
      INTERVENTION(S): Bipronucleate oocytes were grown for up to 144 hours and
      subsequently transferred when at least one embryo attained the expanded
      blastocyst stage. MAIN OUTCOME MEASURE(S): Pregnancy and implantation rates.
      RESULT(S): Pregnancy rates per retrieval were significantly higher for patients
      undergoing their first cycle of in vitro fertilization with blastocyst transfer
      (36%) compared to those undergoing their second (19%) or their third (9%) cycles
      of treatment. Implantation rates per embryo were also higher for first cycles of
      in vitro fertilization with blastocyst transfer (30%) compared to second (18%) or
      third cycles (8%). CONCLUSION(S): Pregnancy and implantation rates decline
      dramatically in repeated cycles of in vitro fertilization with blastocyst
      transfer following one or more unsuccessful cycles of in vitro fertilization with
      blastocyst transfer.

PMID- 11532479
TI  - Human menopausal gonadotropin versus recombinant follicle-stimulating hormone in
      normogonadotropic women down-regulated with a gonadotropin-releasing hormone
      agonist who were undergoing in vitro fertilization and intracytoplasmic sperm
      injection: a prospective randomized study.
AB  - OBJECTIVE: To evaluate clinical and endocrinological effects of intranasal (IN)
      vs. subcutaneous (SC) GnRH-a for pituitary down-regulation combined with hMG vs.
      rFSH. DESIGN: Prospective, randomized study. SETTING: University hospital, IVF
      unit. PATIENT(S): Three hundred seventy-nine normogonadotropic women eligible for
      IVF or ICSI. INTERVENTION(S): Randomization to intranasal (IN) or SC GnRH-a and
      to hMG or rFSH. MAIN OUTCOME MEASURE(S): Oocytes retrieved, embryos developed,
      clinical pregnancy, and delivery rates. Serum hormone concentrations on
      stimulation days 1 (S1) and 8 (S8), and oocyte pick-up (OPU) day. RESULT(S):
      After randomization, four groups were formed: IN/hMG (n = 100), IN/FSH (n = 98),
      SC/hMG (n = 89), and SC/FSH (n = 92). Mean number of oocytes retrieved and of
      transferable and transferred embryos were similar in the four groups. Clinical
      pregnancy rate per started cycle was significantly higher in the IN/HMG group
      than in the SC/FSH group (P<.05) and was intermediate in the two remaining
      groups. Se-LH on S8 in the two SC groups was significantly lower than in the two
      IN groups. Se-E2 on S8 in the SC/FSH group was significantly lower than in the
      other three groups. CONCLUSION(S): The clinical and endocrinological outcome in
      IVF and ICSI-treated normogonadotropic women is significantly influenced by mode
      of down-regulation as well as gonadotropin formulation.

PMID- 11532481
TI  - The immune response during the luteal phase of the ovarian cycle: increasing
      sensitivity of human monocytes to endotoxin.
AB  - OBJECTIVE: To test the hypothesis that during the luteal phase of the human
      ovarian cycle, as compared with the follicular phase, the percentage of cytokines
      producing peripheral monocytes after in vitro stimulation with endotoxin is
      increased. DESIGN: Prospective study. SETTING: Academic research institution.
      PATIENT(S): Women with regular menstrual cycles. INTERVENTION(S): Blood samples
      were collected between days 6 and 9 of the menstrual cycle (follicular phase) and
      between days 6 and 9 of the menstrual cycle following the LH surge (luteal
      phase). MAIN OUTCOME MEASURE(S): Percentages of tumor necrosis factor (TNF)-alpha
      , interleukin (IL)-1 beta-, and IL-12-producing monocytes as well as total white
      blood cell (WBC) count, differential WBC counts, and plasma 17 beta-estradiol and
      progesterone concentrations. RESULT(S): Mean plasma 17 beta-estradiol and
      progesterone concentrations, percentage of TNF-alpha- and IL-1 beta-producing
      monocytes, WBC counts, and granulocyte cell count were significantly increased in
      the luteal phase as compared with the follicular phase of the ovarian cycle. The
      percentage of IL-12-producing monocytes, monocyte count and lymphocyte count did
      not vary between the 2 phases of the ovarian cycle. CONCLUSION(S): Together with
      an increase in progesterone and 17 beta-estradiol during the luteal phase, there
      is an increase in percentage TNF-alpha- and IL-1 beta-producing peripheral
      monocytes after in vitro stimulation with endotoxin as compared with the
      follicular phase of the ovarian cycle. Whether this increased sensitivity of
      monocytes for proinflammatory stimuli during the luteal phase is due to increased
      plasma levels of progesterone or 17 beta-estradiol needs further investigation.

PMID- 11532480
TI  - Discovery of germ cell-specific transcripts by expressed sequence tag database
      analysis.
AB  - OBJECTIVE: To identify transcripts whose expression is restricted to germ cells.
      DESIGN: Expressed sequence tags (ESTs) from unfertilized egg libraries were
      utilized to perform in silico subtraction and identify germ cell-specific
      transcripts. SETTING: Baylor College of Medicine, Houston, Texas. ANIMAL(S):
      C57BL/6J/129SvEv hybrid. INTERVENTION(S): Tissue harvesting from mice. MAIN
      OUTCOME MEASURE(S): Identification of germ cell-specific transcripts. RESULT(S):
      We have used the Unigene collection of mouse cDNA libraries to identify ESTs
      derived from unfertilized egg libraries. A total of 3,499 ESTs were identified
      from Knowles Solter and Ko unfertilized egg cDNA libraries. In silico subtraction
      identified 258 ESTs, which were found in these unfertilized egg libraries, but
      not in adult mouse tissue cDNA libraries. We performed reverse transcription
      polymerase chain reaction (RT-PCR) on multiple adult tissues with 43 selected
      ESTs and found 5 of them where expression was absent in heart, lung, liver,
      brain, spleen, stomach, intestines, kidneys, and uterus, but restricted to
      ovaries and testes. Three ESTs were further analyzed, and they were exclusively
      localized to the oocytes by in situ hybridization. CONCLUSION: We have shown that
      utilization of publicly available ESTs from murine EST libraries is a simple and
      rapid in silico approach to the identification of transcripts preferentially
      expressed in germ cells.

PMID- 11532482
TI  - Peritoneal mesothelial hypoxia during pneumoperitoneum is a cofactor in adhesion
      formation in a laparoscopic mouse model.
AB  - OBJECTIVE: To develop a laparoscopic mouse model to evaluate the hypothesis that
      mesothelial hypoxia during pneumoperitoneum is a cofactor in adhesion formation.
      DESIGN: Prospective randomized trials. SETTING: Academic research center.
      ANIMAL(S): One hundred thirty female Naval Medical Research Institute (NMRI)
      mice. INTERVENTION(S): Adhesions were induced by opposing monopolar lesions in
      uterine horns and pelvic side walls during laparoscopy and evaluated after 7 or
      28 days under microscopic vision during laparotomy. The following
      pneumoperitoneum variables were assessed: duration (10 or 60 minutes),
      insufflation pressure (5 or 15 cm of water), insufflation gas (CO(2) or helium),
      and addition of oxygen (0-12%). MAIN OUTCOME MEASURE(S): Adhesions were scored
      quantitatively and qualitatively for extent, type, and tenacity. RESULT(S):
      Scoring of adhesions 7 or 28 days after laparoscopic surgery was comparable.
      Adhesions increased with duration of pneumoperitoneum and with insufflation
      pressure and decreased with the addition of oxygen. Half-maximal reduction of
      adhesions was obtained at 1.5% oxygen, whereas a maximal reduction required only
      2%-3%. The effect of CO(2) and helium was similar. CONCLUSION(S): These data
      demonstrate the feasibility of the intubated laparoscopic mouse model and confirm
      previous observations in rabbits, indicating that mesothelial hypoxia plays a key
      role in adhesion formation.

PMID- 11532483
TI  - Expression, production, and secretion of vascular endothelial growth factor and
      interleukin-6 by granulosa cells is comparable in women with and without
      endometriosis.
AB  - OBJECTIVE: To investigate the production and secretion of interleukin (IL)-6 and
      vascular endothelial growth factor (VEGF) mRNA and protein by granulosa luteal
      cells (GCs) in vivo and in vitro in women with and without endometriosis. DESIGN:
      Prospective study. SETTING: A private, university-affiliated assisted
      reproduction unit and a university center. PATIENT(S): Women with severe
      endometriosis (n = 6) or without the disease (n = 14) after laparoscopy,
      undergoing in vitro fertilization/intracytoplasmic sperm injection and embryo
      transfer. INTERVENTION(S): GCs were obtained from each aspirate. MAIN OUTCOME
      MEASURE(S): Intracellular and secreted protein, as well as mRNA for both VEGF and
      IL-6 in GCs. RESULT(S): The expression of VEGF and IL-6 mRNAs in vivo and in
      vitro was similar in both groups. Also, GCs from patients with endometriosis
      produced and secreted equal amounts of these proteins compared with controls
      without the disease, either in freshly isolated cells or in 24-hour cultures.
      CONCLUSION(S): The GC function in terms of VEGF and IL-6 production does not seem
      to be altered in patients with endometriosis in comparison with those without
      this condition.

PMID- 11532484
TI  - Validity of radioimmunological methods for determining free testosterone in
      serum.
AB  - OBJECTIVE: To assess serum free testosterone (free T) concentrations in various
      groups of women by means of an ultrafiltration technique (UFT) or two RIAs and to
      investigate the influence of levonorgestrel (LNG) and norethisterone (NET) on
      free T. DESIGN: Experimental study with serum samples from various groups of
      patients. SETTING: Obstetrics and gynecology department of a university.
      PATIENT(S): Samples from 20 normal healthy women, 20 menopausal women, 21
      pregnant women, 23 women using oral contraceptives (OC), 20 hyperandrogenemic
      women, 20 hirsute patients with normal total testosterone (total T), 18 patients
      with acne (normal total T), and 9 women with adrenogenital syndrome (AGS).
      INTERVENTION(S): Blood samples were taken by venipuncture. MAIN OUTCOME
      MEASURE(S): Serum concentrations of free T. RESULT(S): Mean free-T levels
      determined by UFT amounted to 5-6 pg/mL in most groups, except in patients with
      hyperandrogenemia (8.3 pg/mL) or AGS (10.7 pg/mL) and in women using OC (1.9
      pg/mL). The values were twofold to fourfold and threefold to sevenfold higher
      than those determined with the RIAs. The proportion of free T as determined by
      UFT was 0.9-1.2% of total T and was 0.55% during OC treatment. The presence of 10
      ng/mL of LNG or NET increased free-T levels by only 13%. CONCLUSION(S): Serum
      free-T levels determined with RIA are much lower than those measured with the
      UFT. The ratio between the UFT and RIA values may vary depending on the endocrine
      status. In women with normal or elevated sex hormone-binding globulin levels,
      nortestosterone derivatives increase free T levels only slightly.

PMID- 11532485
TI  - Quantification of power Doppler energy and its future potential.
AB  - OBJECTIVE: To test a new software package (Color Quantifier, Kinetic Imaging,
      Liverpool, United Kingdom) that quantifies power Doppler energy and to determine
      its reproducibility. DESIGN: Intraobserver and interobserver reproducibility
      study. SETTING: University tertiary referral center. PATIENT(S): Transvaginal
      power Doppler ultrasound images were recorded from women taking part in a study
      evaluating the physiological vascular changes in the uterus and ovaries during
      the normal menstrual cycle. INTERVENTION(S): Nineteen consecutive frames of
      regions of interest in the uterus, ovary, and follicle, respectively, were
      analyzed by each of four observers on 10 occasions. MAIN OUTCOME MEASURE(S):
      Analysis of variance to determine the image and observer effect as well as the
      intraobserver and interobserver coefficients of variation. RESULT(S): Significant
      image and observer effects were found. However, the image effect was by far the
      largest component of the total variation. The large image-to-image variability
      was expected because the cardiac cycle was included within the 19 frames (images)
      analyzed. The combined intraobserver and interobserver variation, expressed as
      the coefficients of variation, was found to be small for the above indices (as
      low as 1.9%), particularly for total ovary and endometrium. CONCLUSION(S): The
      indices obtained with this color quantification software are reproducible in an
      in vitro setting using prerecorded images. Its applicability as a useful assay in
      the clinical setting requires further evaluation.

PMID- 11532486
TI  - Magnetic resonance imaging and transvaginal ultrasonography for the diagnosis of
      adenomyosis.
AB  - OBJECTIVE: To compare the diagnostic potential of magnetic resonance imaging
      (MRI) and transvaginal ultrasonography (TVS) in the diagnosis of adenomyosis.
      DESIGN: Double blind set-up. SETTING: University medical school. PATIENT(S): We
      studied 106 consecutive premenopausal women who underwent hysterectomy for benign
      reasons. INTERVENTION(S): Transvaginal ultrasonography and MRI were compared with
      histopathologic examination as the golden standard. MAIN OUTCOME MEASURE(S):
      Adenomyosis. RESULT(S): Twenty-two (21%) patients had adenomyosis. The
      sensitivity and specificity were as follows: sensitivity: MRI 0.70 (0.46-0.87)
      and TVS 0.68 (0.44-0.86) (P=.66); specificity: MRI 0.86 (0.76-0.93) and TVS 0.65
      (0.50-0.77) (P=.03). The combination of MRI and TVS was most sensitive (0.89
      [0.64-0.98]), but produced the lowest specificity (0.60 [0.44-0.73]). Adenomyosis
      was not detected by either MRI or TVS at uterine volumes >400 mL. Exclusion of
      uteri >400 mL from the analysis improved the diagnostic precision of MRI, but not
      that of TVS. The diagnostic accuracy at MRI was improved by calculating the
      maximum difference between the thinnest and thickest junctional zone (JZdif)
      (i.e., > or =5-7 mm). CONCLUSION(S): Magnetic resonance imaging was superior to
      TVS for the diagnosis of adenomyosis. Magnetic resonance imaging had a higher
      specificity than TVS, but their sensitivities were in line. The diagnostic
      accuracy of MRI, as that of TVS, was at an intermediate level, but the diagnostic
      accuracy of the former improved by exclusion of uteri >400 mL. The combination of
      MRI and TVS produced the highest level of accuracy for exclusion of adenomyosis,
      but the low specificity may necessitate further investigation of positive
      findings. Measurement of the difference in junctional zone thickness may optimize
      the diagnosis of adenomyosis at MRI.

PMID- 11532487
TI  - Reduction of postsurgical adhesions with Intergel adhesion prevention solution: a
      multicenter study of safety and efficacy after conservative gynecologic surgery.
AB  - OBJECTIVE: To assess the safety and efficacy of the Intergel adhesion prevention
      solution, a 0.5% ferric hyaluronate gel, in reducing adhesions in patients
      undergoing peritoneal cavity surgery by laparotomy with a planned second-look
      laparoscopy. DESIGN: Randomized, third-party blinded, placebo-controlled,
      parallel group. SETTING: Eleven centers in the United States, and five centers in
      Europe. PATIENT(S): Women aged 18-46 years who wanted to retain their fertility.
      INTERVENTION(S): Patients received 300 mL of Intergel solution (n = 143) or
      lactated Ringer's solution (n = 138) as an intraperitoneal instillate at the
      completion of surgery. MAIN OUTCOME MEASURE(S): At second-look laparoscopy 6-12
      weeks later, the presence of adhesions was evaluated at 24 abdominal sites.
      RESULT(S): Patients treated with Intergel solution (n = 131) had significantly
      less adhesions compared to controls (n = 134). Adhesion extent and severity were
      also significantly reduced. The American Fertility Society score for adnexal
      adhesions was reduced 59% in the patients in whom the Intergel solution was used.
      The safety profile of the patients treated with the Intergel solution was
      comparable to those treated with lactated Ringer's solution. CONCLUSION(S): The
      Intergel solution was safe and highly efficacious in reducing the number,
      severity, and extent of adhesions throughout the abdomen after peritoneal cavity
      surgery.

PMID- 11532488
TI  - Determining the best catheter for sonohysterography.
AB  - OBJECTIVE: To compare the characteristics of six different catheters for
      performing sonohysterography (SHG) to identify those that offer the best
      compromise between reliability, tolerability, and cost. DESIGN: Prospective
      study. SETTING: University hospital. PATIENT(S): Six hundred ten women undergoing
      SHG. INTERVENTION(S): We performed SHG with six different types of catheters:
      Foleycath (Wembley Rubber Products, Sepang, Malaysia), Hysca
      Hysterosalpingography Catheter (GTA International Medical Devices S.A., La Caleta
      D.N., Dominican Republic), H/S Catheter Set (Ackrad Laboratories, Cranford, NJ),
      PBN Balloon Hystero-Salpingography Catheter (PBN Medicals, Stenloese, Denmark),
      ZUI-2.0 Catheter (Zinnanti Uterine Injection; BEI Medical System International,
      Gembloux, Belgium), and Goldstein Catheter (Cook, Spencer, IN). MAIN OUTCOME
      MEASURE(S): We assessed the reliability, the physician's ease of use, the time
      requested for the insertion of the catheter, the volume of contrast medium used,
      the tolerability for the patients, and the cost of the catheters. RESULT(S): In
      568 (93%) correctly performed procedures, no statistically significant
      differences were found among the catheters. The Foleycath was the most difficult
      for the physician to use and required significantly more time to position
      correctly. The Goldstein catheter was the best tolerated by the patients. The
      Foleycath was the cheapest whereas the PBN Balloon was the most expensive.
      CONCLUSION(S): The choice of the catheter must be targeted to achieving a good
      balance between tolerability for the patients, efficacy, cost, and the personal
      preference of the operator.

PMID- 11532489
TI  - Unsuspected early pregnancy at hysterosalpingography.

PMID- 11532490
TI  - Birth after intracytoplasmic sperm injection with use of testicular sperm from
      men with Kartagener/immotile cilia syndrome.
AB  - OBJECTIVE: To describe two cases of in vitro fertilization (IVF) and
      intracytoplasmic sperm injection (ICSI) with testicular sperm in men with
      immotile cilia syndromes. DESIGN: Case report. SETTING: A university-based male
      infertility clinic and assisted reproduction unit. PATIENT(S): Two couples with
      male factor infertility due to Kartagener/immotile cilia syndrome.
      INTERVENTION(S): IVF/ICSI with testicular sperm. MAIN OUTCOME MEASURE(S): Semen
      characteristics, sperm viability, fertilization rate, and pregnancy. RESULT(S):
      With testicular sperm, the two pronuclear fertilization rates were 63% and 60% in
      two cases. One case resulted in the birth of normal healthy girl. CONCLUSION(S):
      With testicular sperm, successful oocyte fertilization after ICSI in couples with
      male Kartagener/immotile cilia syndrome is possible despite the lack of sperm
      motility.

PMID- 11532491
TI  - Relationship between salivary progesterone, 17-hydroxyprogesterone, and cortisol
      levels throughout the normal menstrual cycle of healthy postmenarcheal girls.
AB  - OBJECTIVE: To determine the usefulness of salivary P and 17 alpha
      hydroxyprogesterone (17-OHP) for the assessment of ovarian function. In addition,
      salivary cortisol (F) levels were measured to assess the role of the adrenal
      cortex throughout the menstrual cycle. DESIGN: Prospective study. SETTING:
      Outpatients in hospital for children and adolescents. PATIENT(S): Thirty young
      women with regular menstrual cycles. INTERVENTION(S): Saliva collection in the
      early morning from day 1 of menstrual bleeding until next menses. MAIN OUTCOME
      MEASURE(S): Salivary P, 17-OHP, and F measured by RIAs. RESULT(S): During days 1
      12 of the follicular phase, P and 17-OHP levels remained unchanged (P: 9-29.3
      pg/mL; 17-OHP: 8-31 pg/mL). Thereafter, P increased exponentially from day 13
      onward, reaching a plateau (mean +/- SEM, 70.1 +/- 9.0 pg/mL) between day 16 and
      20, followed by a constant decrease until end of the cycle. The 17-OHP levels
      increased between day 14 and 17 (maximum: 45.8 +/- 4.5 pg/mL), decreasing rapidly
      thereafter. The F levels remained unchanged (follicular: 7.5 +/- 1.1 ng/mL;
      luteal 7.2 +/- 1.1 ng/mL). There was a significant correlation between P and 17
      OHP (r(2) = 0.43; P<.001). When calculating ratios of P/F and 17-OHP/F, linear
      regression yielded a much stronger correlation (r(2) = 0.74; P<.001), although F
      did not show any correlation to P or 17-OHP. CONCLUSION(S): Changes in salivary
      17-OHP levels throughout the menstrual cycle reflect ovarian but not adrenal
      function.

PMID- 11532492
TI  - Successful birth after transfer of vitrified human blastocysts with use of a
      cryoloop containerless technique.
AB  - OBJECTIVE: Clinical application of vitrification for the cryopreservation of
      human blastocysts. DESIGN: Clinical trial of vitrification of human blastocysts.
      SETTING: Private assisted reproductive technology clinic. PATIENT(S):
      Supernumerary blastocysts after fresh blastocyst transfer were vitrified for
      subsequent transfer. INTERVENTION(S): Culture of pronuclear embryos to the
      blastocyst stage in sequential media and subsequent vitrification of
      supernumerary blastocysts using a cryoloop technique. MAIN OUTCOME MEASURE(S):
      Clinical outcome after transfer of vitrified blastocysts. RESULT(S): A total of
      60 vitrified blastocysts from 21 patients were warmed, and the survival rate at 2
      hours after warming was 63%. Six clinical pregnancies were achieved after 19
      transfers. One healthy baby was born, four pregnancies are ongoing, and one ended
      in miscarriage. CONCLUSION(S): Human blastocysts can be successfully vitrified by
      suspension on a small nylon loop and a direct plunge into liquid nitrogen. A
      delivery and ongoing pregnancies prove the safety of this method. This report
      documents the first successful pregnancy and delivery achieved by blastocyst
      vitrification using the cryoloop containerless technique.

PMID- 11532493
TI  - Monopaternal superfecundation of quintuplets after transfer of two embryos in an
      in vitro fertilization cycle.
AB  - OBJECTIVE: To present the first genetically proven identity of quintuplets in an
      IVF treatment cycle after transferring only two embryos. DESIGN: Case report.
      SETTING: IVF unit and obstetrics department of university-affiliated general
      hospital. PATIENT(S): Twenty-five-year-old patient undergoing IVF treatment for
      unexplained infertility. INTERVENTION(S): In vitro fertilization with
      intracytoplasmic sperm injection performed on 50% of oocytes, resulting in
      successful production of nine early-cleavage embryos. Transfer of two embryos on
      day 3 and freezing of the remaining embryos. MAIN OUTCOME MEASURE(S): Development
      of five separate embryonic sacs. Fetal reduction of three embryos at 12 weeks of
      gestation. RESULT(S): Successful completion of the twin pregnancy and full
      genetic analysis of the three embryos and the twins that were born at term.
      CONCLUSION(S): Despite transferring only two embryos, superfecundation occurred,
      resulting in five embryos. Genetic analysis can be used to determine paternity
      and identity of all the embryos.

PMID- 11532494
TI  - Transition to parenthood among in vitro fertilization patients at 2 and 9 months
      postpartum.

PMID- 11532495
TI  - Effect of paclitaxel on primordial follicular reserve in mice.

PMID- 11532514
TI  - Myelodysplasia with fibrosis: a distinct entity?

PMID- 11532496
TI  - The ineffective loading process of the embryo transfer catheter alters
      implantation and pregnancy rates.

PMID- 11532515
TI  - Exposure to armament wastes and leukemia: a case-control study within a cluster
      of AML and CML in Germany.
AB  - An unusually high incidence of acute myeloid leukemia (AML) and chronic myeloid
      leukemia (CML) concentrated in a specific locality of a region in Germany
      motivated a descriptive incidence study in that region which showed a near 10
      fold increased risk of CML among males but not among females (Kolb G, Becker N,
      Scheller S, Zugmaier G, Pralle H, Wahrendorf J, Havemann K. Increased risk of
      acute myelogenous leukemia (AML) and chronic myelogenous leukemia (CML) in a
      County of Hesse, Germany, Soc Prev Med 1993;38:190-195). Since a serious
      environmental contamination of areas in this locality with armament wastes
      containing toluene-derivatives has been known for a long time, the hypothesis
      arose that TNT production and the related severe contamination of soil and water
      might be responsible for the observed higher risk. We carried out a case-control
      study within the cluster to test this hypothesis. Overall, the results do not
      confirm the hypothesis. There is an indication of a relationship of an increased
      odds ratio with the exposure for a small group of persons who lived at a
      particular site in one of the two communities involved during the peak phase of
      TNT production during the 1940s. However, this finding is spurious and cannot
      explain the large majority of cases which occurred in that area in the 1980s. At
      the moment, no other explanation can be given for the increased risk of leukemias
      in that area.

PMID- 11532516
TI  - A minor E-selectin ligand, CD65, is critical for extravascular infiltration of
      acute myeloid leukemia cells.
AB  - Adhesive ligands on acute myeloid leukemic (AML) blasts may mediate
      transmigration and extravascular infiltration. In this study, 30 AML samples were
      examined for expression and density of adhesion antigens. By univariate analysis,
      four patients with extravascular infiltration showed significantly higher
      expression of CD2, CD11a, CD11b, CD11c, CD15, CD65, CD86, and HLA-DR as compared
      with patients without infiltration. These four patients also showed significantly
      higher density of CD11a, CD11b, CD11c, CD15 and CD65 expression. By multivariate
      analysis, CD65 expression was the only significant independent risk factor for
      infiltration, suggesting that this is a critical adhesion molecule for
      extravascular AML infiltration.

PMID- 11532517
TI  - Frequent loss of heterozygosity in the region of D1S450 at 1p36.2 in
      myelodysplastic syndromes.
AB  - To understand the underlying mechanisms in myelodysplastic syndromes (MDS) by
      identifying target tumor suppressor genes, we performed a detailed deletional
      mapping of the short arm of chromosome 1 in 38 paired samples of bone marrow and
      peripheral blood obtained from individuals with MDS by PCR amplification of a
      total of 23 highly informative microsatellite sequences. We identified the
      commonly deleted region between D1S508 and D1S244. LOH of this region was found
      in five patients (13%). In addition, LOH at 1p was associated with a poor
      clinical outcome, suggesting that the deletion of a gene in this region may be
      involved in the course of this disease. By analyzing the chromosomal map of this
      region, we found TNFRSF12 as a candidate tumor suppressor gene. However, our
      search for mutations in this gene did not identify somatic mutations in MDS. Our
      findings are consistent with the possible existence of an as-yet unknown tumor
      suppressor gene in this region that is altered in MDS.

PMID- 11532518
TI  - Clinical significance of fragile histidine triad gene expression in adult acute
      lymphoblastic leukemia.
AB  - The FHIT (fragile histidine triad) gene, which is located on 3p14.2 and believed
      to be a tumor suppressor gene, has been reported to lose its expression in
      several solid tumors and hematologic malignancies, including acute lymphoblastic
      leukemia (ALL). The clinical relevance of the loss of FHIT expression in ALL is
      not known. We used western blot and solid-phase radioimmunoassay (RIA) to analyze
      Fhit protein expression in 90 patients with ALL. Eighteen (20%) of the tested
      patients had severely reduced Fhit protein (undetectable by western blot), and 43
      patients (47%) had levels lower than those detected in normal bone marrows.
      Interestingly, seven patients (8%) expressed very high levels (>two-fold the
      level detected in normal bone marrow). A parallel pattern of FHIT RNA expression
      was also observed. Of the 90 patients, 39 received induction therapy consisting
      of hyper-CVAD (hyperfractionated cyclophosphamide, vencristine, adriamycine, and
      dexamethasone) and were followed in our institution. Patients with low Fhit
      protein levels showed no statistically significant difference in survival or
      complete remission duration (CRD) from patients with normal levels (P=0.12 and
      0.24, respectively). Our study confirms that FHIT is aberrantly expressed in ALL,
      but suggests it does not have a role as a prognostic factor. Studies with large
      numbers of patients and evaluation of the mechanisms of FHIT function in ALL are
      needed.

PMID- 11532519
TI  - Smoking and acute myeloid leukemia: associations with morphology and karyotypic
      patterns and evaluation of dose-response relations.
AB  - This case-control study of tobacco smoking and acute myeloid leukemia (AML),
      emphasizing specific associations with morphologic and cytogenetic subtypes,
      comprised smoking histories for 333 cases and 351 controls. Smoking status (ever
      smokers versus life-long non-smokers) showed no evident effect on AML risk.
      However, an effect of smoking was indicated at high cumulative smoking doses
      (pack-years), e.g. 40 pack-years was associated with an odds ratio (OR) of 1.5
      [95% confidence interval (CI) 1.0-2.3]. Among morphologic subtypes, the smoking
      associated OR for acute erythroleukemia was 8.9 (95% CI 1.0-76). No clear
      associations between smoking and cytogenetic subtypes of AML were observed.

PMID- 11532520
TI  - Increase in platelet-large cell ratio in chronic myeloid leukemia.

PMID- 11532521
TI  - High affinity interleukin-3 receptor expression on blasts from patients with
      acute myelogenous leukemia correlates with cytotoxicity of a diphtheria toxin/IL
      3 fusion protein.
AB  - Diphtheria fusion proteins are a novel class of agents for the treatment of
      chemotherapy resistant AML. We prepared DT(388)IL3 composed of human interleukin
      3 (IL3) fused to the catalytic and translocation domain of diphtheria toxin
      (DT(388)) and assessed its activity on patient AML blasts. The number and
      affinity of IL3 receptors in circulating blasts was measured using a radiolabeled
      IL3 agonist (SC-65461). Ninety-two percent of patients' blasts had both high and
      low affinity IL3 receptors. DT(388)IL3 cytotoxicity (>1 log cell kill) was seen
      in nine of 25 samples (36%). There was a significant correlation between
      DT(388)IL3 log cell kill and blast high affinity IL3 receptor density (P=0.0044).
      These results show that specific high affinity IL3 binding is one factor
      important in the sensitivity of patients' leukemic blasts to DT(388)IL3.

PMID- 11532522
TI  - Isofenphos induced metabolic changes in K562 myeloid blast cells.
AB  - The organophosphate pesticide, isofenphos, is associated with human myeloid
      leukemia. In this study we describe metabolic changes in K562 myeloid blast cells
      from exposure to varying concentrations of isofenphos using the stable [1,2
      13C(2)]glucose isotope as the single tracer and biological mass spectrometry.
      Isofenphos (1, 10, 100 microg/ml/72 h) treated K562 cells showed increases of
      10.7, 33.8 and 39.7% in lactate production as well as a 14.2% increase (1
      microg/ml/72 h) in 13C incorporation into nucleic acid ribose from glucose.
      Concomitantly, we observed a decrease in glucose oxidation and the synthesis of
      glutamate, palmitate and stearate from glucose. Our results demonstrate that this
      organophosphate pesticide exerts a leukemogenic effect by the recruitment of
      glucose carbons for nucleic acid synthesis thus promoting proliferation
      simultaneous with poor differentiation. The imbalanced metabolic phenotype with a
      severe defect in glucose oxidation, lipid and amino acid synthesis concurrent
      with de novo synthesis of nucleic acids in response to isofenphos treatment
      conforms to the invasive proliferating phenotype observed in TGF-beta treated
      lung epithelial carcinoma cells.

PMID- 11532523
TI  - Cyclopentenyl cytosine induces apoptosis and increases cytarabine-induced
      apoptosis in a T-lymphoblastic leukemic cell-line.
AB  - Cyclopentenyl cytosine (CPEC) is a nucleoside-analogue that decreases the
      concentrations of cytidine triphosphate (CTP) and deoxycytidine triphosphate
      (dCTP) in leukemic cells by inhibiting the enzyme CTP synthetase, resulting in a
      decreased synthesis of RNA and DNA. Low concentrations of dCTP facilitate the
      phosphorylation of 1-beta-D arabinofuranosyl cytosine (araC) and the
      incorporation of arabinofuranosyl cytosine triphosphate (araCTP) into DNA.
      Apoptosis and necrosis were analyzed by flow cytometric detection of fluorescence
      labeled Annexin V in a human T-lymphoblastic MOLT-3 cell-line after incubations
      with CPEC and/or araC. CPEC induced apoptosis and necrosis in a concentration-
      (50-300 nM) and time-dependent (8-16 h) way. The observed necrosis proved to be
      secondary to apoptosis as the caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp
      fluoromethylketone (zVAD-fmk) completely blocked the CPEC-induced apoptosis and
      necrosis. Coincubation of various concentrations of CPEC and araC for 16h showed
      a significant additive effect on the occurrence of apoptosis and (secondary)
      necrosis. In contrast, a preincubation with 37.5 nM of CPEC for 24 h, which by
      itself caused only minor apoptosis (4%), followed by a coincubation for 16 h with
      62.5 nM of araC (7% of apoptotic cells), showed a synergistic effect on the
      induction of apoptosis (27%, P<0.001). Growth-inhibition experiments with CPEC
      and araC under various conditions showed an additive effect on the araC-induced
      growth-inhibition after 48 h. The results indicate that the cytotoxicity of araC
      can be increased in T-lymphoblasts by CPEC.

PMID- 11532524
TI  - Bone marrow stromal cells regulate caspase 3 activity in leukemic cells during
      chemotherapy.
AB  - The interaction between leukemic cells and stromal cells of the bone marrow
      microenvironment has been shown to enhance leukemic cell survival during exposure
      to chemotherapeutic agents. In the current study we investigated whether
      association of B lineage acute lymphoblastic leukemic cells with human bone
      marrow stromal cells altered caspase activation during chemotherapy treatment.
      Following treatment with Ara-C or VP-16 in vitro, caspase 3 activity in leukemic
      cells was consistently reduced by co-culture of leukemic cells with human bone
      marrow stromal cell layers. These observations suggest that the protective effect
      of the bone marrow microenvironment on leukemic cells may be due, in part, to
      regulation of caspase 3 activity.

PMID- 11532525
TI  - Regression of engineered myeloma cells secreting interferon-gamma-inducing factor
      is mediated by both CD4(+)/CD8(+) T and natural killer cells.
AB  - IL-18 is a novel cytokine that stimulates T and NK cell activity and has potent
      antitumor effects. In this study, a mouse IL-18 gene was transfected into the
      mouse myeloma cell line J558. Our data demonstrated that (i) inoculation of
      0.5x10(6) engineered tumor cells J558/IL-18 into syngeneic mice induced a Th1
      dominant immune response and resulted in tumor regression in all 8/8 mice; (ii)
      the IL-18 antitumor effect was significantly decreased in mice depleted of either
      the CD4(+), or CD8(+), or NK cell subset, respectively but was completely
      abrogated in mice depleted of both CD4(+) and CD8(+) T cells; (iii) in vivo
      neutralization of IFN-gamma was accompanied by the growth of J558/IL-18 tumor in
      all the mice; and (iv) the J558/IL-18 tumor regression further induced protective
      immunity against a subsequent challenge by the parental J558 tumor, which is
      mediated by CD8(+) T cells as examined in the cytotoxicity assay in vitro and in
      the animal study in vivo. Taken together, our findings indicate that: (i) IL-18
      can induce antitumor immune responses mediated by both CD4(+)/CD8(+) T cells and
      NK cells; and (ii) it is associated with IFN-gamma production. This study thus
      highlights the potential utility of IL-18 as an antitumor agent, a role that it
      can fulfil alone or in combination with other immunomodulatory cytokines such as
      IL-12.

PMID- 11532526
TI  - KG-1 and KG-1a model the p15 CpG island methylation observed in acute myeloid
      leukemia patients.
AB  - p15 and p16 are tumor suppressor genes that have 5' CpG islands and both are
      subject to hypermethylation associated with their transcriptional inactivation in
      hematological malignancies. In this study, we used sodium bisulfite sequencing to
      obtain a complete map of the 5-methylcytosine status of 80 CpGs covering
      approximately 900 bp in the 5' p15 CpG island, and 53 CpGs covering approximately
      700 bp in the 5' p16 CpG island in the hematopoietic cell lines HL60, KG-1, and
      KG-1a, two normal human bone marrow samples (NBM), and eight cytosine arabinoside
      (ara-C)-resistant adult acute myeloid leukemia (AML) patients. We found
      methylation of the p15 CpG island in 75% of the AML cases studied spread
      throughout the 5' region analyzed but only minimal methylation of p15 in NBM.
      Further, the p16 CpG island was not aberrantly methylated in NBM or the eight AML
      patients studied. Two distinct modes of p15 methylation in AML were identified,
      variegated and complete. Interestingly, KG-1 and KG-1a model the methylation of
      p15 observed in AML, where KG-1 methylation is variegated and KG-1a methylation
      is complete. Both KG-1 and KG-1a had no detectable p15 mRNA or protein. These
      results demonstrate that rather than continuous increases in p15 methylation,
      surprisingly two punctuated modes of aberrant p15 methylation, variegated and
      complete, were observed in vitro and in vivo. Thus aberrant methylation of tumor
      suppressor genes is not a binary switch but in the case of p15 occurs in two
      independent and stable states.

PMID- 11532527
TI  - Serotonin and bipolar disorder.
AB  - With the emergence of specific pharmacological probes for various serotonin (5
      HT) receptors and radio-ligands for central 5-HT, it has now become possible to
      investigate its role in the pathogenesis of bipolar disorder more closely. This
      paper critically reviews the scientific literature regarding the relationship
      between bipolar disorder and serotonergic systems. The evidence suggests that
      central serotonergic activity is reduced in the depressive phase of bipolar
      disorder. Similar findings have been reported in bipolar patients when euthymic,
      indicating that that lower 5-HT activity could be a trait marker for bipolar
      disorder. Findings reported in the manic phase of this illness are inconsistent.

PMID- 11532528
TI  - Bipolar II depression in late life: prevalence and clinical features in 525
      depressed outpatients.
AB  - BACKGROUND: Late-life bipolar II depression has not been well studied. The aim of
      the present study was to find the prevalence of late-life (50 years or more)
      bipolar II depression among unipolar and bipolar depressed outpatients, and to
      compare it with bipolar II depression in younger patients, looking for
      differences supporting the subtyping of bipolar II depression according to age at
      onset. METHODS: Consecutive 525 patients presenting for treatment of a major
      depressive episode were interviewed with the Structured Clinical Interview for
      DSM-IV, the Montgomery Asberg Depression Rating Scale, and the Global Assessment
      of Functioning Scale. RESULTS: Among patients less than 50 years, 53.4% had
      bipolar II depression. Among patients 50 years or more, 32.9% had bipolar II
      depression (significant difference). Atypical features were present in 60.9% of
      bipolar II patients less than 50 years, and in 26.1% of those 50 years or more
      (significant difference). Bipolar II patients 50 years or more had significantly
      higher age at onset than those less than 50 years. Bipolar II and unipolar
      patients 50 years or more were not significantly different, apart from
      comorbidity. Bipolar II patients less than 50 years had significantly more
      atypical features than unipolar ones. LIMITATIONS: Single interviewer, single
      nonblind assessment, cross-sectional assessment, exclusion of substance abuse and
      severe personality disorder patients, comorbidity not systematically assessed,
      modification of DSM-IV duration criterion for hypomania. CONCLUSIONS: Findings
      suggest that bipolar II depression and atypical features are less common in late
      life. Differences in age at onset and atypical features support the subtyping of
      bipolar II depression according to age at onset.

PMID- 11532529
TI  - CAG repeats of CTG18.1 and KCNN3 in Korean patients with bipolar affective
      disorder.
AB  - BACKGROUND: Trinucleotide repetition combined with variable penetrance of
      expression could be responsible for the complex transmission pattern observed in
      bipolar affective disorder (BPAD). The purpose of this study was to investigate
      the association of excess longer allele of KCNN3 and CTG18.1 in the patients with
      BPAD. METHODS: CAG/CTG repeat distribution in KCNN3, CTG 18.1 and ERDA1 was
      examined and the copy number of ligation product in repeat expansion detection
      (RED) was measured in Korean bipolar patients in comparison to ethnically matched
      healthy controls. RESULTS: No significant difference was found in the allele
      distribution of those repeats between bipolar patients and controls. Ligation
      product size in RED was not increased in bipolar patients. However, the copy
      number of ligation product in RED was highly correlated with CAG/CTG copies of
      ERDA1 (P=0.0001), partly with CTG 18.1 (P=0.04), but not with KCNN3. CONCLUSIONS:
      A longer CAG repeat alleles of KCNN3 or CTG 18.1 may not be a risk factor for
      BPAD in Korean population and the copy number of ligation product in RED in the
      patients with BPAD is influenced by the longer allele of CAG/CTG of ERDA1 or CTG
      18.1.

PMID- 11532530
TI  - Impact of early onset bipolar disorder on family functioning: adolescents'
      perceptions of family dynamics, communication, and problems.
AB  - OBJECTIVE: This research investigated the impact of adolescent onset bipolar
      illness on perceived family functioning in stabilized bipolar I (B) and unipolar
      (U) probands, and normal controls (C). METHOD: Sample N=119: 44 bipolar 1(17 M,
      27 F), 30 unipolar (9 M, 21 F), and 45 controls (19 M, 26 F). Mean ages: 19.9,
      18.5 and 18.2 years, respectively. INSTRUMENTS: Family Adaptability and Cohesion
      Scale (FACES II), Parent-Adolescent Communication Scales (PACS), Social
      Adjustment Inventory for Children and Adolescents (SAICA). RESULTS: There were no
      significant group or sex differences between controls and mood disordered youth-
      assessed intermorbidly--in ratings of relationship with either parent. Bipolars
      acknowledged significantly more minor conflicts with parents than either
      unipolars or controls. Ratings by mood disordered subjects were significantly
      less positive in terms of shared activities and communication with siblings. Mood
      disordered youth and controls were not differentiated on the basis of family
      adaptability, and all family cohesion scores were within population norms. No
      significant group differences were observed in communication with parents.
      LIMITATIONS: This self-report study was conducted intermorbidly, does not include
      objective measures of family functioning, nor does it assess the effect of
      psychiatric illness in other family members on family functioning. CONCLUSIONS:
      Assessed intermorbidly, bipolar adolescents' perceptions of family dynamics do
      not seem to diverge significantly from controls. Further research is needed to
      investigate the impact of adolescent bipolar illness on family life during acute
      phases of the illness, as well as the effect on family functioning of psychiatric
      disorders in other family members.

PMID- 11532531
TI  - Dysthymic disorder: clinical characteristics in relation to age at onset.
AB  - BACKGROUND: The variability in the clinical presentation of dysthymia has given
      rise to a rich debate in literature, and various hypotheses have been proposed.
      One is that the clinical presentation differs in relation to age at onset. The
      aim of the study was to evaluate differences in socio-demographic and clinical
      characteristics in a sample of patients with dysthymia (DSM-IV), in relation to
      age at onset. METHOD: 84 consecutive outpatients with a diagnosis of dysthymia
      (DSM-IV) were studied. All subjects were evaluated by a semistructured clinical
      interview and the following rating scales: HAM-A, HAM-D, MADRS, Paykel's
      Interview for Recent Life Events. RESULTS: 23.8% of the sample had early-onset
      (<21 yrs) dysthymia. Patients with early-onset disorder were significantly
      younger at the observation, more frequently female and single. They had a
      significantly longer duration of illness and in a significantly higher percentage
      had already received a specialist treatment before admission in the present
      trial. No differences in the frequency of symptoms were observed. A significantly
      higher percentage of patients with late-onset disease reported at least one
      stressful event in the year preceding the onset of dysthymia. A positive history
      of major depression was significantly more common among the early-onset group;
      social phobia, panic disorder and conversive disorder were also more frequent in
      this group. The late-onset patients frequently presented generalized anxiety
      disorder, substance abuse and somatization disorder. LIMITATION: The study is
      retrospective and enrolls a limited number of cases. CONCLUSIONS: The present
      study agrees with other reports on the differences in clinical presentation of
      dysthymia according to age at onset. Although they are not actually related to
      age at onset, some interesting findings emerged in the symptomatological
      characterization of the disorder, referring to the diagnostic criteria proposed
      in DSM-IV.

PMID- 11532532
TI  - SPECT and neuropsychological performance in severe depression treated with ECT.
AB  - BACKGROUND: In severe depression, studies of regional cerebral blood flow (rCBF)
      by SPECT have not produced uniform results. The association between changes in
      SPECT and electroconvulsive therapy (ECT) has shown somewhat conflicting data. No
      data are available on benzodiazepine receptor function SPECT studies in ECT.
      METHODS: Twenty drug-resistant adult inpatients fulfilling the DSM-IIIR criteria
      for major depression were studied by SPECT (rCBF by relative ECD uptake in all,
      and benzodiazepine receptor function by iomazenil uptake in five subjects) before
      and 1 week after clinically successful bitemporal ECT. Clinical and
      neuropsychological test scores were used as references for the possible changes
      in SPECT. RESULTS: An increased perfusion after ECT was observed in right
      temporal and bilateral parietal cortices, whereas no reductions in relative ECD
      uptake were seen after ECT. Iomazenil-SPECT revealed a highly significant
      increase in the benzodiazepine receptor uptake in all studied cortical regions
      except temporal cortices. CONCLUSIONS: Clinically successful ECT was associated
      with changes in vascular perfusion and GABAergic neurotransmission, providing new
      evidence for the mechanism of action of ECT and for the neurobiology of severe
      drug-resistant depression.

PMID- 11532533
TI  - Reflections of depression in acoustic measures of the patient's speech.
AB  - BACKGROUND: The literature on acoustic measures of voice in depression is
      reviewed. Authors have separated results derived from studies of automatic
      speech, such as counting or reading, from free speech. Free speech requires
      cognitive activity such as word finding and discourse planning in addition to the
      motor activity of automatic speech. Also, results have been less ambiguous if
      homogeneous groups of agitated or retarded depressed patients were examined.
      METHODS: These distinctions are applied to the results of a 12-week double-blind
      treatment trial that compared response to nortriptyline (25-100 mg/day) with
      sertraline (50-150 mg/day). Twelve male and ten female elderly depressed patients
      and an age-matched normal control group (n=19) were studied. Patients were
      divided into retarded or agitated groups on the basis of ratings. Results from
      measures of fluency (speech productivity and pausing) and prosody (emphasis and
      inflection) are described. RESULTS: Depressed patients showed less prosody than
      the normal subjects. Improvement in the retarded group was reflected in briefer
      pauses but not longer utterances. There was a trend in the agitated group for
      improvement to be reflected in the utterance but not the pause measure.
      CONCLUSIONS: Clinical impressions are substantially related to acoustic
      parameters. Temporal changes associated with depression appear to reflect the
      depressed state whereas prosodic features seem to reflect a depressed trait.
      Acoustic measures of the patient's speech may provide objective procedures to aid
      in the evaluation of depression. Limitations of the study are discussed.

PMID- 11532534
TI  - Suicidal behavior in twins: a replication.
AB  - OBJECTIVE: Our two previous reports showed that monozygotic (MZ) twins were
      significantly more concordant for both completed suicide and attempted suicide
      than dizygotic (DZ) twins. We wished to replicate the finding that MZ co-twins
      showed greater concordance for suicidal behavior. METHOD: We collected a new
      series of 28 twin pairs in which one twin had committed suicide. RESULTS: We
      found that 4 of the 13 MZ twin pairs were concordant for suicidal behavior
      compared with 0 of the 15 DZ twin pairs (P=0.035). CONCLUSIONS: These data
      confirm our previous reports that MZ co-twins show greater concordance for
      suicidal behavior than DZ co-twins, consistent with genetic influence.

PMID- 11532535
TI  - The hypothalamic-pituitary-thyroid axis in agoraphobia, panic disorder, major
      depression and normal controls.
AB  - BACKGROUND: Much interest has been drawn to the investigation of the hypothalamic
      pituitary-thyroid (HPT)-axis in patients suffering from depression or panic
      disorder. However, there is no data concerning agoraphobia. METHODS: Patients
      with panic disorder, agoraphobia, major depression were compared to normal
      controls (total n=88) in respect to HPT axis, obtaining basal TSH and
      administering a TRH test. RESULTS: Normal controls and agoraphobics showed
      significantly higher Delta(max) TSH than depressives and panic patients. There
      were no differences between agoraphobics and normal controls. CONCLUSIONS:
      Agoraphobia, unlike depression or panic disorder, seems to be less biologically
      determined in respect to the HPT-axis.

PMID- 11532536
TI  - Association study of nicotinic-receptor variants and major depressive disorder.
AB  - BACKGROUND: Depressive patients are more likely to smoke than the general
      population and nicotine was found to reduce the incidence and severity of
      depressive symptoms in many studies. These findings suggest that nicotinic
      acetylcholine receptors (nAChRs) may be implicated in major depressive disorder.
      We tested the hypothesis that the allelic variant, 2 bp deletion, of the
      partially duplicated alpha7 nAChR gene confers susceptibility to major depressive
      disorder. METHODS: We genotyped alpha7 nAChR in 72 patients with major depressive
      disorder and 103 normal controls. RESULTS: The distribution of the partially
      duplicated alpha7 nAChR genotypes (P=0.027) and alleles (P=0.037) suggests a
      modest difference between depressive patients and controls. LIMITATIONS: The -2
      bp allele is thought to be present only in the duplicated exon 6, and the impact
      of the partially duplicated alpha7 nAChR and its -2 bp variant remain to be
      determined. CONCLUSIONS: The -2 bp allele of partially duplicated alpha7 nAChR
      may have an influence on the risk for development of major depressive disorder.
      The levels of significance achieved are modest and the findings must be
      replicated in other studies.

PMID- 11532537
TI  - The impact of repetitive transcranial magnetic stimulation on pituitary hormone
      levels and cortisol in healthy subjects.
AB  - BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is a new
      therapeutic tool in the treatment of affective disorders but only few studies on
      its safety exist. We aimed to determine the impact of rTMS on
      (neuro)endocrinological serum levels by a placebo-controlled cross-over study.
      METHODS: 23 healthy subjects were stimulated by rTMS in a typical paradigm used
      in the treatment of depression (coil placed over left dorsolateral prefrontal
      cortex, 10 and 20 Hz stimulation). Placebo, infrathreshold, and suprathreshold
      stimulation were applied in random order. The serum levels of cortisol,
      prolactin, FSH, and TSH were measured before and after stimulation. RESULTS:
      After infrathreshold stimulation, cortisol and TSH serum levels decreased mildly
      but significantly. All other stimulations had no significant impact on hormone
      levels. In female, but not in male, subjects placebo stimulation yielded a
      significant increase of prolactin. CONCLUSIONS: rTMS as applied for the treatment
      of depression leads to only very mild and safe changes of hormones. These
      changes, in particular the decrease of cortisol levels, might explain in part the
      efficacy of rTMS.

PMID- 11532538
TI  - S-100B is increased in melancholic but not in non-melancholic major depression.
AB  - BACKGROUND: Recent evidence suggests that neurodegeneration may be involved in
      the pathophysiology of major depression. The astroglial peptide S-100B was shown
      to be increased in many diseases causing neuronal cell damage or degeneration.
      METHOD: S-100B plasma levels were determined in 28 patients with major depression
      and 28 matched healthy controls using an immunofluorometric sandwich assay.
      RESULTS: Patients suffering from melancholic depression showed significantly
      increased S-100B levels compared to healthy controls while non-melancholic
      patients demonstrated normal levels. LIMITATIONS: Medication of patients varied.
      The differentiation between melancholic and non-melancholic patients was
      performed clinically without using a standardized instrument. CONCLUSIONS:
      Neurodegeneration or axonal remodeling may be involved in the pathogenesis of
      melancholic depression.

PMID- 11532539
TI  - Exciting new drugs on the horizon - eplerenone, a selective aldosterone receptor
      antagonist (SARA).
AB  - Despite major advances many cardiovascular disorders remain poorly controlled. As
      a result the search for newer agents goes on. Anti-neurohormonal agents have been
      the most successful agents: beta-blockers, ACE inhibitors and angiotensin
      receptor blockers. To these we now add anti-aldosterone strategies with the
      phenomenal success of spironolactone in reducing mortality in severe heart
      failure. A more recent and more selective aldosterone receptor antagonist has
      been developed, eplerenone, and it shows considerable promise in managing and
      preventing the complications of hypertension. It may have a role both being anti
      fibrotic and anti-neurohormonal in mild to moderate heart failure, in post-MI
      left ventricular dysfunction and in progressive renal disease. The EPHESUS trial
      which randomised patients with heart failure due to impaired left ventricular
      systolic function aims to randomise 6,200 patients to eplerenone or placebo on
      top of standard therapy and follow subjects until 1,012 deaths have occurred
      (approx. 2.5 years of follow up). This and other trials with the novel strategy
      of selective aldosterone antagonism are eagerly awaited. The beneficial effects
      established by the earliest anti-neurohormonal agents give us confidence that
      further benefits could be obtained by this intellectual strategy.

PMID- 11532540
TI  - Coronary angiography using 4 French catheters.

PMID- 11532541
TI  - Predictors of atrial flutter with 1:1 conduction in patients treated with class I
      antiarrhythmic drugs for atrial tachyarrhythmias.
AB  - OBJECTIVES: The purpose of the study was to look for the predictor factors of
      atrial proarrhythmic effects of class I antiarrhythmic drugs. BACKGROUND: Class I
      antiarrhythmic drugs may induce or exacerbate cardiac arrhythmias. The predictors
      of ventricular proarrhythmia are known. The predictors of atrial flutter with 1:1
      conduction are unknown. METHODS: Clinical history, EGG, signal-averaged EGG
      (SAECG) and electrophysiologic study were analysed in 24 cases of 1:1 atrial
      flutter with class I AA drugs and in 100 control patients without history of 1:1
      atrial flutter with class I AA drugs. RESULTS: The ages of patients varied from
      46 to 78 years. Underlying heart disease was present in nine patients. The
      surface EGG revealed the presence of a short PR interval (PR<0.13 ms), visible in
      leads V5, V6 in eight (35%) patients with normal P wave duration; in other
      patients with prolonged P wave duration, PR seemed normaL On SAECG recording,
      there was a pseudofusion between P wave and QRS complex. The electrophysiologic
      study revealed some signs indicating a rapid AV nodal conduction (short AH
      interval or rate of 2nd degree AV block at atrial pacing >200 beats/mm) in 19 of
      the 23 studied patients. All patients, except one, had at least one sign
      indicating a rapid AV nodal conduction (short PR and/or P wave-QRS complex
      continuity on SAECG). In the control group, seven patients (7%) had a short PR
      interval (P<0.01) and 11 (11%) had a pseudofusion between P wave and QRS complex
      on SAECG (P<0.001). The P wave-QRS complex pseudofusion on SAECG had a
      sensitivity of 100% and a specificity of 89% for the prediction of an atrial
      proarrhythmic effect with class I antiarrhythmic drug. CONCLUSION: We recommend
      avoiding class I AA drugs in patients with a short PR interval on surface EGG and
      to record SAECG in those with apparently normal PR interval to detect a
      continuity between P wave and QRS complex, which could indicate a rapid AV nodal
      conduction, predisposing to 1:1 atrial flutter with the drug.

PMID- 11532542
TI  - Atrial flutter with 1:1 atrioventricular conduction related to class I
      antiarrhythmic drugs for atrial tachyarrhythmias: from mechanism to predicting
      factors.

PMID- 11532543
TI  - The underreporting of results and possible mechanisms of 'negative' drug trials
      in patients with chronic heart failure.
AB  - Large drug trials have become very important to determine which drugs should be
      used in the treatment of patients with chronic heart failure (CHF). When these
      trials showed "positive" results, publication of the data soon followed, leading
      to a substantial impact on prescription patterns. In the case of "negative"
      results, many times they were not published, or were reported as an abstract or
      as short paper disclosing only the main findings. In this article we will discuss
      some of these trials that were conducted in the last 10 years, since we believe
      they may provide insight into the pathophysiology and treatment options in CHF.

PMID- 11532544
TI  - Association between the severity of heart failure and the susceptibility of
      myocytes to apoptosis in patients with idiopathic dilated cardiomyopathy.
AB  - BACKGROUND: Bcl-2 proto-oncogene, an inhibitor of apoptosis and Bax proto
      oncogene, an inducer of apoptosis play critical roles in the molecular circuit
      controlling apoptosis in cardiac muscle. The ratio of Bax to Bcl-2 proto-oncogene
      determines survival or death after an apoptotic stimulus. We speculated that
      susceptibility of myocytes to apoptosis determined as the Bax/Bcl-2 ratio might
      vary with the severity of heart failure. METHODS AND RESULTS: We studied
      immunohistochemically 108 endomyocardial biopsy specimens from 30 patients with
      idiopathic dilated cardiomyopathy (mild heart failure, n=14; moderate or severe
      heart failure, n=16) with the use of Bcl-2 and Bax monoclonal antibodies. The
      expression of each protein was determined semiquantitatively as the fraction of
      myocytes labeled with specific monoclonal antibodies using a digital morphometric
      analysis system. Patients with mild heart failure showed significantly increased
      Bax/Bcl-2 ratio than the patients with advanced heart failure (1.59+/-1.26 vs.
      0.34+/-0.43, P=0.002). The expression of Bcl-2 was found to be independent of the
      severity of heart failure whereas the expression of Bax was significantly higher
      in patients with mild heart failure compared to the patients with moderate or
      severe heart failure (52.1+/-29.3 vs. 21.6+/-22.4%, P=0.005). Additionally,
      Bax/Bac-2 ratio was inversely correlated with the mitral E-interventricular
      septum distance, left ventricular end-systolic and end-diastolic diameter.
      CONCLUSION: The susceptibility of myocytes to apoptosis is significantly
      increased in the early phase of heart failure but it decreases with worsening of
      the disease due to depressed expression of Bax onco-protein. Increased myocyte
      susceptibility to apoptosis may have a role in the transition from mild heart
      failure to severe in patients with idiopathic dilated cardiomyopathy.

PMID- 11532545
TI  - QT dispersion within the first 6 months after an acute myocardial infarction:
      relationship with systolic function, left ventricular volumes, infarct related
      artery status and clinical outcome.
AB  - INTRODUCTION: We analysed QT dispersion within the first 6 months postinfarction,
      its relationship with the main established risk stratifiers and its clinical
      value. METHODS AND RESULTS: In 55 patients with a first Q-wave myocardial
      infarction the 12-lead electrocardiogram was scanned and digitised for analysis
      of QT dispersion (QT maximum-QT minimum) at first day (72 [61-96] ms), first week
      (69 [47-90] ms), first month (67 [46-88] ms) and sixth month (47 [40-74] ms;
      P<0.0001 vs. first day). Cardiac catheterization was performed at first week and
      at sixth month; QT dispersion was not related to ejection fraction, left
      ventricular volumes, infarct related artery status or contractile reserve
      (improvement of the infarcted area with low-dose dobutamine); no relation was
      found between QT dispersion decrease from first week to sixth month with regional
      systolic function improvement. Finally, during a mean follow-up period of 35+/-22
      months QT dispersion was not independently related to clinical events.
      CONCLUSION: QT dispersion decreases progressively during the first months after
      myocardial infarction. These changes should be taken into account to define cut
      off values of clinical interest in this phase. This variable does not seem
      related to the classic prognosis predictors. In a nonselected postinfarction
      population it has a low clinical value.

PMID- 11532546
TI  - Early dobutamine echocardiography for the assessment of coronary stenosis after
      first Q-wave myocardial infarction.
AB  - We assessed the accuracy of early dobutamine stress echocardiography to detect
      infarct-related coronary artery and multivessel disease in patients with first Q
      wave myocardial infarction after withdrawal of cardioactive drugs. Dobutamine
      atropine echocardiography was performed in 91 consecutive patients (mean age 59+/
      6 years) 7+/-4 days after myocardial infarction. Dobutamine was infused at
      incremental doses of 5, 10, 20, 30 to 40 microg/kg/min each one dose for 3 min.
      Peak heart rate was 134+/-17 bpm. All patients underwent coronary angiography
      before discharge. Sensitivity, specificity and accuracy of ischemic and biphasic
      response to detect residual stenosis of infarct-related coronary artery were 70,
      92 and 73%, respectively. The sensitivity, specificity and accuracy of ischemic
      or biphasic response were similar in the vascular territories of left anterior
      descending (74, 86 and 75%, respectively), right (67, 100 and 70%, respectively)
      and circumflex coronary arteries (64, 100, and 69%, respectively). Sensitivity,
      specificity and accuracy of heterozonal wall motion abnormalities for multivessel
      coronary artery disease were 64, 82 and 76%, respectively. Dobutamine stress
      echocardiography is sensitive and specific in detecting residual coronary
      stenosis and multivessel disease in patients with first Q-wave myocardial
      infarction. The test is safe even without pharmacological protection.

PMID- 11532547
TI  - Chemokines in patients with ischaemic heart disease and the effect of coronary
      angioplasty.
AB  - Percutaneous coronary transluminal angioplasty (PTCA) may release inflammatory
      mediators such as chemokines. Monocyte chemoattractant protein-1 (MCP-1) and
      eotaxin (EOX) are monocyte- and eosinophil-specific chemokines involved in the
      inflammation and pathogenesis of coronary atherosclerosis. A total of 28 patients
      undergoing elective PTCA, 20 coronary artery disease (CAD) patients undergoing
      coronary angiography and 28 healthy controls were studied. In PTCA patients
      before the procedure, MCP-1 plasma levels (441+/-64 pg/ml) were similar to those
      of CAD patients (430+/-24 pg/ml), and significantly higher compared with controls
      (145+/-17 pg/ml, P<0.01). MCP-1 rose significantly after 3 and 6 months following
      PTCA (696+/-89 and 876+/-86 pg/ml, respectively, P<0.01 vs. before PTCA). EOX
      plasma levels (155+/-14 pg/ml) were similar to those of CAD patients (157+/-14
      pg/ml), but significantly higher compared with controls (83.2+/-10 pg/ml,
      P<0.05). EOX rose significantly 24 h (273+/-41 pg/ml, P<0.05) but not 3 months
      after PTCA (160+/-20 and 158+/-19 pg/ml, respectively). These findings indicate
      that chemokine-induced monocyte- and eosinophil-specific chemoattraction is
      stimulated in patients with coronary artery disease. MCP-1 levels remain
      significantly elevated for at least 6 months following elective PTCA, suggesting
      an inflammatory stimulation.

PMID- 11532548
TI  - Suitability of venous and arterial conduits used for coronary artery bypass
      grafting in conjunction with coronary disease risk factors.
AB  - BACKGROUND/STUDY OBJECTIVES: We studied patients undergoing coronary artery
      bypass grafting. Risk factors for coronary disease were studied in conjunction
      with the histopathologic findings of the grafts prior to implantation. Our aim
      was to correlate the histologic condition of the grafts and evaluate the
      morphological changes in conjunction with existing risk factors. DESIGN/PATIENTS:
      In 10 candidates for surgical revascularization (nine males, mean age 60.8
      years), the risk factor profile was studied (smoking, dyslipidaemia,
      hypertension, diabetes, family history) and the Body Mass Index was calculated.
      Of a total of 14 grafts, 10 were saphenous vein grafts and four left internal
      thoracic artery grafts. Histologic samples were studied under optical and
      electron microscopy. We studied the intima morphology and thickness, the width of
      the intercellular spaces, the texture of the subendothelial layer, the
      endothelial status, and the condition of the basal lamina. Histopathological
      changes were correlated with risk factors. RESULTS: Histopathological changes
      were observed in the wall structure of all grafts. The most important changes
      were found in the venous grafts, notably: intima thickening, existence of foam
      cells in the intima, widening of the intercellular spaces, subendothelial oedema,
      degeneration and detachment of endothelial cells, and wide multilayered basal
      lamina. The co-existence of two or more risk factors seems to exarcerbate
      morphological changes. CONCLUSION: Morphological changes are present principally
      in the walls of venous but also arterial conduits, even prior to implantation.
      These changes may be attributable to preparation techniques and preservation
      conditions of the grafts, but they could additionally be induced by coexisting
      risk factors. It is conceivable that these alterations could perhaps precipitate
      and accelerate atherosclerotic changes, inducing lumen narrowing or even
      occlusion of the graft postoperatively.

PMID- 11532549
TI  - Head-up tilt test without intravascular cannulation in children and adolescents.
AB  - Previous studies of head-up tilt test have shown that testing at high degrees
      lacks specificity in children. We suspected that the high false positive rate
      might be related to the intravascular catheter and other maneuvers incorporated
      in the test and therefore studied the sensitivity and specificity of standing and
      HUT at 80 degrees without any invasive procedure and other maneuvers in children
      and adolescents. Twenty three patients (11.8+/-2.7 years) with recurrent typical
      neurally mediated syncope and 35 normal control children (11.6+/-3.0 years)
      underwent motionless standing for 15 min and tilting to 80 degrees for 30 min.
      Continuous finger arterial pressure monitoring and ECG were performed during the
      test. Eight (35%) of the 23 patients developed symptoms of near syncope during
      motionless standing. Thirteen (57%) of them had positive results at 80 degrees
      tilting for 30 min. The symptoms of syncope were not always corresponding to
      excessive haemodynamic changes. None of the controls developed any symptoms or
      excessive hemodynamic changes. Without intravascular instrumentation and other
      autonomic maneuvers, active motionless standing or HUT at 80 degrees for 30 min
      is highly specific but of limited sensitivity for the investigation of vasovagal
      syncope.

PMID- 11532550
TI  - Catastrophic effect of the mitral prosthetic valve thrombosis in a malignant
      case.

PMID- 11532551
TI  - Streptococcal meningitis in adults: therapeutic outcomes and prognostic factors.
AB  - Thirty-eight patients with streptococcal meningitis, aged 17-75 years, have been
      identified over a period of 13.5 years. Among these 38 patients, 35 had community
      acquired infections, and the other three had nosocomial infections. Twelve of the
      38 patients were found to have postneurosurgical forms and 26 to have spontaneous
      forms. These 38 cases of streptococci included Streptococcus (S.) pneumoniae in
      19 cases, viridans group streptococci in 13, non-A, non-B, and non-D streptococci
      in three, Group D streptococci in one, and Group B streptococci (S. agalactiae)
      in two. Although one case was found to have penicillin-resistant S. pneumoniae
      PRSP in 1994, multi-antibiotic resistant strains were rare in this study.
      Therapeutic outcomes varied according to the different species of streptococci.
      In this study, the overall mortality rate was 34%. In the multiple logistic
      regression analysis, only initial consciousness level and the presence of seizure
      were strongly associated with the mortality rate even after other potentially
      confounding factors were adjusted for. Early diagnosis and the use of appropriate
      antibiotics are essential for survival.

PMID- 11532552
TI  - CT stereotaxy guided lateral trans-cerebellar programmable fourth ventriculo
      peritoneal shunting for symptomatic trapped fourth ventricle.
AB  - A trapped fourth ventricle is a rare clinico-radiological entity producing
      symptoms suggestive of a progressive posterior fossa mass lesion. It is mainly
      reported in children as a late complication of lateral ventricular shunting to
      relieve infantile post-meningitic or post-hemorrhagic hydrocephalus. Optional
      treatment of the trapped fourth ventricle remains controversial. Placement of
      fourth ventricular shunting via a conventional midline approach can be fraught
      with complications in about 40% of the patients. Authors report a successful CT
      Stereotaxy guided high pressure (80 mm H(2)O) programmable fourth ventriculo
      peritoneal shunting via a lateral trans-cerebellar approach in a 14-year-old girl
      with a trapped fourth ventricle, which occurred as a late complication of
      ventriculo-peritoneal shunting in her infancy. Her preoperative symptoms of
      raised intracranial pressure, bobble-head doll syndrome and bilateral abducens
      palsies completely improved following the surgery. Lateral trans-cerebellar
      stereotactic placement of the fourth ventricular catheter and the use of high
      pressure (low flow) programmable shunt (to avoid complications associated with
      over drainage) are beneficial in some patients with trapped fourth ventricle.

PMID- 11532553
TI  - Visual evoked potentials in Parkinson's disease-correlation with clinical
      involvement.
AB  - A total of 18 patients with Parkinson's disease were evaluated clinically and by
      transient checker-board VEP study. There were significant differences between
      bradykinesia (P<0.01), rigidity (P<0.02), and tremor (P<0.05) subscores of the
      more and less severely affected sides. There were no asymmetry of VEP latency or
      amplitude between the more and less severely affected sides by stimulation of the
      corresponding eye. There were no significant correlations between the VEP latency
      or amplitude and any of the clinical features except the bradykinesia scores. The
      bradykinesia scores on the more severely involved side (r: 0.57; P=0.014) and
      less severely involved side (r: 0.82; P=0.00003) showed medium to high degree
      positive correlations with VEP amplitudes by stimulation of the corresponding
      eye. By studying monocular fullfield responses our data can only suggest that
      there is no prechiasmal asymmetry. The positive correlation between the VEP
      amplitude and bradykinesia score might indicate that D2 receptors dominate in the
      retina.

PMID- 11532554
TI  - Autoimmune thyroiditis and acquired demyelinating polyradiculoneuropathy.
AB  - Guillain-Barre syndrome (GBS) and Miller-Fisher syndrome (MFS) are variant forms
      of acquired demyelinating polyradiculoneuropathy. Their concurrence with immune
      disorders of the thyroid is infrequent. We report on a 7.5-year-old girl in whom
      a subclinical thyroiditis was concurrently detected to GBS and a 70-year-old
      woman with Hashimoto's thyroiditis (HT) who had recurrent MFS. Even though
      autoimmune thyroiditis is associated with many autoimmune disorders more often
      than would be expected by chance alone, its concurrence with immune disorders of
      the peripheral nerve is less frequently reported. The calculated coincidental
      concurrence of acquired demyelinating polyradiculoneuropathy (in both variants,
      MFS and GBS) and autoimmune thyroiditis (as in the present cases) was extremely
      low (0.0004%), thus suggesting common pathogenic mediators.

PMID- 11532555
TI  - Acute disseminated encephalomyelitis following aseptic meningoencephalitis.
AB  - A previously healthy 50-year-old man developed aseptic meningoencephalitis with
      clinical manifestations including fever, headache, seizure, Wernicke aphasia,
      right hemiplegia, and blindness in the left eye. One and one-half months after
      remission of meningoencephalitis, marked ataxia and psychiatric symptoms became
      apparent. Magnetic resonance imaging revealed multiple new lesions involving the
      basal ganglia, thalamus, white matter, and cerebellum. Despite these
      developments, cerebrospinal fluid findings continued to improve except for
      excessive content of myelin basic protein. Within 2 weeks, steroid therapy
      dramatically resolved the ataxic symptoms and disseminated lesions.

PMID- 11532556
TI  - Subacute diencephalic angioencephalopathy: biopsy diagnosis and radiological
      features of a rare entity.
AB  - Subacute diencephalic angioencephalopathy (SDAE) is a rare and fatal disease of
      unknown etiology that involves the thalami bilaterally. To date, there have been
      four cases reported, in which the diagnosis was established only after post
      mortem examination of the brain. We report two male patients, ages 69 and 41
      years, who presented with progressive dementia and somnolence. Radiological
      evaluation revealed enhancing lesions involving both thalami. The differential
      diagnosis included a number of neoplastic, inflammatory and vascular processes.
      In both cases, pathological evaluation of biopsy specimens suggested the
      diagnosis of SDAE. Despite supportive care, the disease progressed rapidly and
      both patients died within weeks after initial presentation. The diagnosis was
      confirmed at autopsy in both cases. SDAE is a rare cause of bithalamic disease
      that can be mistaken for a neoplasm as well as a number of conditions that
      necessitate different treatment choices. The histopathological findings can
      establish the diagnosis when combined with radiological and clinical information.
      This report emphasizes the utility of stereotactic biopsy in early diagnosis of
      SDAE.

PMID- 11532557
TI  - Normalization of creatine kinase level during pregnancy in idiopathic
      hyperCKemia.
AB  - A 34-year-old previously healthy woman with no remarkable family history
      developed asymptomatic hyperCKemia at age 26. Over the next 6 years, hyperCKemia
      persisted (502-2562 IU/l; normal range<180). A muscle biopsy showed minimal
      nonspecific myopathy. Genetic analysis of blood and muscle samples showed no
      abnormality in the dystrophin gene. At age 33, she became pregnant for the first
      time and serum creatine kinase (CK) was normal at 170 IU/l in the third
      trimester. After delivery, hyperCKemia reappeared (715-2620) while her baby
      tested normal for CK. This is the first report of idiopathic hyperCKemia
      associated normalization of serum CK level during pregnancy, which has been
      reported in carriers of Duchenne muscular dystrophy.

PMID- 11532558
TI  - Protean infectious types and frequent association with neurosurgical procedures
      in adult Serratia marcescens CNS infections: report of two cases and review of
      the literature.
AB  - Serratia marcescens is a rare pathogen of adult central nervous system (CNS)
      infection. We report on the clinical features and therapeutic outcomes of two
      adult patients with such infections. The clinical characteristics of 13 other
      reported adult cases are also included for analysis. The 15 cases were nine males
      and six females, aged 19-83 years, in whom, underlying post-neurosurgical states
      and ear operation were noted in 93% (14/15). Fever and conscious disturbance were
      the most common clinical manifestations of these 15 cases, followed by
      hydrocephalus, seizures, and wound infections. The manifestation types were
      protean, including meningitis and focal suppurations such as brain abscess,
      cranial and spinal epidural abscess, cranial subdural abscess, and infected
      lumbar pseudomeningocele. One case of S. marcescens CNS infection was diagnosed
      postmortem; the other 14 were diagnosed by the positive culture from CSF or pus.
      Antibiotic therapy with or without neurosurgical intervention was the management
      strategy in 14/15 cases. The therapeutic results showed a high mortality rate.

PMID- 11532559
TI  - Failure of one-day praziquantel treatment in patients with multiple
      neurocysticercosis lesions.
AB  - A recently described one-day regimen of praziquantel (PZQ) therapy for
      neurocysticercosis (NCC), three doses of 25 mg/k given at 2 h intervals, was
      applied in eight patients with viable NCC cysts without any evidence of
      inflammation. Resolution of lesions in computed tomography (CT) was observed in
      all five patients with a single cyst, whereas all cysts survived in three
      patients with multiple brain parasites. One-day praziquantel is a good regimen
      for patients with a single viable brain cysticercus but is poorly effective for
      multiple cysts.

PMID- 11532560
TI  - Provocative tests in different stages of carpal tunnel syndrome.
AB  - The frequency of positive results of four conventional provocative tests (Phalen
      sign, Tinel sign, wrist extension and pressure provocation test) was evaluated in
      179 patients with clinical and electrophysiological findings consistent with
      idiopathic carpal tunnel syndrome (CTS), 147 control subjects and 39 patients
      with polyneuropathy. The diagnostic accuracy was evaluated for each test alone
      and in combination and the sensitivity correlated with the clinical and
      electrophysiological severity of CTS. For comparison of the CTS group with the
      control group, none of the tests reached sufficient diagnostic accuracy. The same
      was found for comparison of the CTS group with the polyneuropathy group, the
      Tinel sign being the least accurate. The combination of signs was not found to be
      more useful than single signs. The sensitivity of all signs was much less in
      severe clinical stages of CTS, especially for tests that increase the intra
      carpal canal pressure. Traditional provocative tests, such as those tested here,
      have limited or no value for distinguishing patients with and without CTS, one
      reason being that their sensitivity depends largely on the clinical and
      electrophysiological severity of CTS. This correlation may also explain the
      contradictory results in the literature.

PMID- 11532561
TI  - Symptom expectation after minor head injury. A comparative study between Canada
      and Lithuania.
AB  - OBJECTIVES: The purpose of the present study is to compare the frequency and
      nature of expected symptoms in Lithuania (a country where the chronic post
      concussive syndrome is largely unknown) with that in Canada. METHODS: A symptom
      checklist was administered to two subject groups selected from local companies in
      Kaunas, Lithuania, and Edmonton, Canada, respectively. Subjects were asked to
      imagine having suffered head trauma with loss of consciousness in a motor vehicle
      accident, and to check off symptoms they expected might arise from the injury.
      For symptoms they anticipated, they were asked to select the period of time they
      expected those symptoms to persist. RESULTS: In both the Lithuanian and
      Edmontonian groups, the pattern of symptoms anticipated closely resembled the
      acute symptoms commonly reported by accident victims with minor head injury. Yet,
      while many Edmontonians also anticipated symptoms to last months or years, very
      few Lithuanian subjects selected any symptoms as being likely to persist in a
      chronic manner. CONCLUSIONS: In Lithuania, despite the frequent experience of
      minor head injury in motor vehicle accidents, there is a very low rate of
      expectation of any chronic sequelae from such an injury, contrasting greatly with
      the response shown in Canada, where the prevalence of the chronic post-concussive
      syndrome is higher. Symptom expectation in some countries may be an important
      factor in the development of the chronic post-concussive syndrome.

PMID- 11532562
TI  - Cerebral vein thrombosis and prothrombin gene (G20210A) mutation.
AB  - Recently, prothrombin gene mutation G20210A has been associated with elevated
      thrombosis risk and rarely with cerebral vein thrombosis (CVT). Three patients
      are described who had this genetic predisposition and who developed CVT in an
      unusual constellation with other factors. In the first patient, the intake of
      valproic acid (VPA) may have played an aggravating role in the development of
      CVT; in the second patient diagnosis of coagulation disorder was made during
      pregnancy consultation 6 years after CVT; in the third patient the CVT occurred
      at the age of 78 years. In patients with CVT, coagulation-examinations should
      include tests for the prothrombin gene (G20210A) mutation.

PMID- 11532563
TI  - Acute bilateral cerebellar infarction in the territory of the medial branches of
      posterior inferior cerebellar arteries.
AB  - The most frequent type of cerebellar infarcts involved the posterior inferior
      cerebellar artery (PICA) and superior cerebellar artery territories but bilateral
      involvement of lateral or medial branches of PICA is extremely rare. In this
      report, we present a 55-year-old male who admitted to hospital with vomiting,
      nausea and dizziness. On examination left-sided hemiparesia and ataxic gait were
      detected. Infarct on bilateral medial branch of PICA artery territories was found
      out with cranial magnetic resonance imaging (MRI) technique and 99% stenosis of
      the left vertebral artery was found out with digital subtraction arteriography.
      The patient was put on heparin treatment. After 3 weeks, his complaints and
      symptoms had disappeared except for mild gait ataxia.

PMID- 11532564
TI  - Objective pulsatile tinnitus caused by intrapetrous dissecting aneurysm.
AB  - Intrapetrosal dissections is a special kind of intracranial dissection since it
      is located intracranially but extradurally. Only three reports of spontaneous
      intrapetrosal dissection have been published so far, the posttraumatic
      intrapetrosal dissections caused by penetrating or blunt trauma not included.
      Based on the clinical and radiological presentation a treatment with
      anticoagulantia (a coumarine derivative) was successfully installed. A short
      review of the major studies concerning intracranial dissection is presented. Firm
      guidelines for the treatment cannot be provided based on these data but the
      etiology of the dissection, whether it was posttraumatic or spontaneous, seems to
      be important. The diagnostic problem of pulsatile tinnitus is briefly discussed.

PMID- 11532565
TI  - Low-temperature sterilization using gas plasmas: a review of the experiments and
      an analysis of the inactivation mechanisms.
AB  - Utilizing an ionized gas (plasma) to achieve sterilization is an alternative to
      conventional sterilization means as far as sterilization of heat-sensitive
      materials and innocuity of sterilizing agents are concerned. The literature on
      plasma sterilization is reviewed. A major issue of plasma sterilization is the
      respective roles of UV photons and reactive species such as atomic and radicals.
      Insight into this matter is obtained by analyzing the survival curves of
      microorganisms. In contrast to classical sterilization where such plots show a
      unique straight line, plasma sterilization yields survival diagrams with two or
      three different linear segments. Three basic mechanisms are involved in the
      plasma inactivation of microorganisms: (A) direct destruction by UV irradiation
      of the genetic material of microorganisms; (B) erosion of the microorganisms atom
      by atom, through intrinsic photodesorption by UV irradiation to form volatile
      compounds combining atoms intrinsic to the microorganisms; (C) erosion of the
      microorganisms, atom by atom, through etching to form volatile compounds as a
      result of slow combustion using oxygen atoms or radicals emanating from the
      plasma. In some cases, etching is further activated by UV photons, increasing the
      elimination rate of microorganisms. These mechanisms make plasma sterilization
      totally different from classical sterilization techniques and suggest its use to
      inactivate nonconventional infectious agents such as the abnormal prions.

PMID- 11532566
TI  - Evaluation of polymeric nanoparticles composed of cholic acid and methoxy
      poly(ethylene glycol).
AB  - Amphiphilic polymeric conjugate based on cholic acid (CA) as the hydrophobic
      component and methoxy poly(ethylene glycol) (MPEG) as the hydrophilic component
      was synthesized using a 1,1'-carbonyldiimidazole (CDI) mediated conjugation.
      Fluorescence spectroscopy measurements suggested that CA and MPEG (abbreviated as
      CE) conjugate was associated in water to form polymeric core-shell type
      nanoparticles with a critical association concentration (CAC) value of 0.063 g l(
      1). From the transmission electron microscope (TEM) observation, CE nanoparticles
      were almost spherical with a size range of approximately 10-30 nm in the dried
      state, which was in agreement with the result from particle size measurement
      using photon correlation spectroscopy (PCS). Clonazepam (CNZ) was physically
      loaded into the CE nanoparticles with a 16.2 wt.% loading. CNZ release was pseudo
      zero-order in kinetic terms for up to 3 days.

PMID- 11532567
TI  - Development and characterization of cross-linked poly(malate) microspheres with
      dipyridamole.
AB  - Biodegradable cross-linked microspheres containing up to 63 wt.% of the active
      substance were obtained in a polycondensation process between D,L-malic acid and
      the tetrahydroxy compound dipyridamole. The in vitro release mechanism from
      biodegradable cross-linked microspheres has been studied. It was found that
      dipyridamole was released due to two-step hydrolysis of the ester bonds of the
      network. Initially, the only product of the hydrolytic degradation was found to
      be an oligomeric ester fraction with M(w)=1000 Da. The release of the free drug
      started after 8 days due to a further hydrolysis of the oligomers in solution. It
      was found that blood plasma enzymes in rats did not affect the hydrolytic
      processes. Biodegradable poly(malate) microspheres containing an anti-aggregating
      agent dipyridamole can be considered as a novel drug delivery system for a
      prolonged period of time implying a future parenteral application.

PMID- 11532568
TI  - Use of pure t-butanol as a solvent for freeze-drying: a case study.
AB  - 1-(2-Chloroethyl)-3-sarcosinamide-1-nitrosourea, (SarCNU) (NSC-364432) is a new
      antitumor drug that is of interest to the National Cancer Institute. It is
      intended for use as an intravenous injection. Although SarCNU is sufficiently
      soluble in water to obtain the desired dosage, it is highly unstable. Its T(90)
      in aqueous solution at room temperature is less than 6 h. Neat tertiary butyl
      alcohol (TBA), a low toxicity, high vapor pressure and low melting solvent, was
      determined to be an excellent freeze-drying medium. Lyophilization of SarCNU from
      pure TBA produces a uniform cake composed of needle-shaped crystals. Thermal
      analysis and gas chromatography indicate that the cake contains less than 0.001%
      residual solvent. The SarCNU cake can be readily reconstituted with either water
      or an aqueous solution of 40% propylene glycol and 10% ethanol. The reconstituted
      solutions are stable for 4 and 13 h, respectively.

PMID- 11532569
TI  - Transdermal permeation of apomorphine through hairless mouse skin from
      microemulsions.
AB  - The in vitro transdermal absorption of apomorphine from microemulsions was
      studied using the skin of the hairless mouse as a membrane. Two microemulsions
      (no. 1 and 2) were prepared and thickened both containing 3.9% of apomorphine
      hydrochloride. The lipophilicity of the drug was increased by forming apomorphine
      octanoic acid ion-pairs. The fluxes of the drug from the microemulsions through
      hairless mouse skin were 100 microg h(-1) cm(-2) from no. 1 and 88 microg h(-1)
      cm(-2) from no. 2. Apomorphine in microemulsions, protected from light with
      antioxidants, showed no degradation for up to 6 months.

PMID- 11532570
TI  - Effect of nicotinamide on the properties of aqueous HPMC solutions.
AB  - The effect of nicotinamide on the properties of aqueous
      hydroxypropylmethylcellulose (HPMC) solutions was studied. Rheological studies
      showed that solutions of HPMC of concentration less than 3.0 w/v.% did not form
      gels and exhibited Newtonian flow patterns at 25 degrees C. The inclusion of
      nicotinamide increased the viscosity of HPMC solutions, which indicates that
      nicotinamide expanded the HPMC coils in aqueous solution. When the temperature of
      the solutions was raised, they formed gels that were detected by viscometry and
      oscillation tests as abrupt increases in viscosity, storage modulus and loss
      modulus and an abrupt decrease in loss angle. Nicotinamide exhibited a salting in
      effect on the HPMC solutions resulting in an increase in gelation temperatures
      and cloud points. These effects are considered to be due to the hydrogen-bonding
      of nicotinamide to HPMC molecules, which was suggested by a shift to a longer
      wavelength of the UV spectra of aqueous nicotinamide solutions by the addition of
      HPMC. These results suggested that nicotinamide has affinity with the hydrophilic
      groups of HPMC.

PMID- 11532571
TI  - Effect of pharmacotechnical design on the in vitro interaction of ketoconazole
      tablets with non-systemic antacids.
AB  - In certain polytherapy programs, ketoconazole can be administered with some
      antacids that could modify its dissolution rate and reduce its absorption leading
      to therapeutic failures. The aim of this work was to evaluate the influence of
      some excipients on this interaction in vitro. In this way, six formulations of
      directly compressible ketoconazole tablets were developed. The results confirmed
      that the dissolution rate of ketoconazole tablets was significantly reduced in
      the presence of antacids. Nevertheless this interaction was remarkably avoided in
      some of the formulations checked and in some conditions. In this way, the
      inclusion of a disintegrant (sodium starch glycolate) not only increased the
      dissolution rate of ketoconazole in the tablets, as expected, but it also
      modified the degree in which the dissolution rate was decreased in the presence
      of antacids. It was proved that a suitable selection of the excipients and
      therefore the modification in the rate in which the drug was released, could play
      an important role to modify a pharmacokinetic interaction based on a reduction of
      the solubility of the drug as a function of the pH value of the medium.

PMID- 11532572
TI  - Effect of pH on skin permeation enhancement of acidic drugs by l-menthol-ethanol
      system.
AB  - The effect of pH on the skin permeation enhancement of three acidic drugs by the
      l-menthol-ethanol system was investigated. The total flux of acidic drugs from
      the system remarkably varied over the pH range 3.0-8.0, and the permeation
      enhancement factor depended on the system pH and drug. A skin permeation model,
      which consists of two permeant (unionized and ionized) species, two system (oily
      and aqueous) phases, and two permeation (lipid and pore) pathways, was developed.
      The assumptions were made that only the unionized species can distribute to the
      oily phase and transport via the lipid pathway. The model explained the
      relationship between the concentration of drug in the aqueous phase and system
      pH. The skin permeability data were also described by the model and permeability
      coefficients corresponding to the physicochemical properties of permeant were
      calculated for the lipid and pore pathways. The model simulation showed that the
      permeation of acidic drugs occurred from the aqueous phase and the oily phase
      acted as a reservoir. Whether the total flux increased with increase of pH was
      dependent on the lipophilicity of drug. These results suggest that the pH of l
      menthol-ethanol system should be given attention to elicit the maximum permeation
      enhancement.

PMID- 11532573
TI  - Stability of amorphous indomethacin compounded with silica.
AB  - The stability of indomethacin (IM) compounded with SiO(2) either by co-grinding
      or by melt-quenching was examined by recrystallization kinetics under the
      conditions 30 degrees C and 11% relative humidity. A decrease of the
      recrystallization rate with and without an appreciable induction period was
      observed in both compounds. Higher stability of amorphous IM compounded with
      SiO(2) was attained by prolonged co-grinding than by melt-quenching. This was
      explained by the stronger chemical interaction at the interface between IM and
      SiO(2) by co-grinding, as revealed by (29)Si and (13)C solid state NMR.
      Incomplete co-grinding with the rest of the crystalline state, however, made the
      amorphous state appreciably unstable, since the remaining crystallites serve as
      seeds for recrystallization.

PMID- 11532574
TI  - Lactosaminated and intact N-succinyl-chitosans as drug carriers in liver
      metastasis.
AB  - The biodistributions of fluorescently labeled N-succinyl-chitosan (Suc-FTC) and
      lactosaminated N-succinyl-chitosan (Lac-Suc-FTC) after i.v. administration to
      mice intravenously inoculated with M5076 cells were investigated at 3 and 12 days
      post-inoculation. At both time points, Lac-Suc-FTC was specifically localized to
      the liver. However, the area under the concentration-time curve in the liver
      decreased gradually by progress of the liver metastasis. At 3 days post
      inoculation, Suc-FTC showed good retention in the systemic circulation and was
      little distributed to the liver. However, at 12 days post-inoculation, Suc-FTC
      was eliminated relatively fast from the systemic circulation and gradually
      accumulated in the liver. The antitumor effects of mitomycin C (MMC), Lac-Suc-MMC
      conjugate (Lac-Suc-MMC) and highly succinylated Suc (Suc(II))-MMC conjugate
      (Suc(II)-MMC) were examined on single i.v. administration for both metastatic
      stages. For administration at 3 days post-inoculation, Lac-Suc-MMC alone tended
      to elongate significantly the lifespan at a lower dose (0.4 mg eq. MMC/kg), and
      MMC, Suc(II)-MMC and Lac-Suc-MMC increased significantly the lifespan at a higher
      dose (10 mg eq. MMC/kg). However, at 12 days post-inoculation (late stage of
      metastasis), neither MMC nor the conjugates were effective even at the higher
      dose (10 mg eq. MMC/kg). Both carriers, Suc showing systemic long-circulation and
      Lac-Suc with an ability of liver-specific localization, are thought to be drug
      carriers with potentialities for therapeutics at early stage of metastasis.

PMID- 11532575
TI  - Application of linear mixed effects models to the evaluation of dissolution
      profiles.
AB  - The performance of linear mixed effects models for the comparison of dissolution
      profiles is examined. This type of model is frequently used by statisticians, but
      is rather unknown to people that work in dissolution laboratories. Hence, an
      extensive theoretical part was introduced to make the methodology more
      accessible. Firstly, repeated measures ANOVA is discussed, followed by the "real"
      linear mixed effects models. The theory is applied to two types of dissolution
      data: one corresponding to an immediate and another to a slow release
      formulation. We tried to use as much as possible the standard settings of the
      statistical software (S-plus). Suggestions are given to solve problems
      encountered during model fitting. It was found that the statistical limits are
      much more discriminative than the similarity factor.

PMID- 11532576
TI  - Effect of poly-L-arginine on the nasal absorption of FITC-dextran of different
      molecular weights and recombinant human granulocyte colony-stimulating factor
      (rhG-CSF) in rats.
AB  - The effect of poly-L-arginine (poly-L-Arg) on the in vivo nasal absorption of
      FITC-dextrans with a mean molecular weight ranging from 4.3 to 167 kDa and
      recombinant human granulocyte colony-stimulating factor (rhG-CSF) in rats were
      studied. When FITC-dextrans were co-administered intranasally with 1.0 w/v% poly
      L-Args of different molecular weight (MW, ca. 45.5 and 92 kDa, poly-L-Arg (50)
      and poly-L-Arg (100)), the bioavailability (F(infinity)) increased markedly
      compared with that after administration of FITC-dextran alone. However, the
      F(infinity) decreased exponentially with the increasing molecular weight of FITC
      dextrans. There was no significant difference between the enhanced nasal
      absorption of FITC-dextrans achieved by the co-administration of poly-L-Arg (50)
      and poly-L-Arg (100). Moreover, the relationship between the F(infinity) and the
      molecular weight of FITC-dextrans indicated that the molecular weight of protein
      drugs, which exhibited efficient absorption with poly-L-Arg, was about 20 kDa,
      when the lower limit of bioavailability for developing a potent transnasal
      delivery system was assumed to be about 10%. Indeed, the nasal absorption of rhG
      CSF, which has a molecular weight of 18.8 kDa, was also increased after co
      administration of 1.0 w/v% poly-L-Arg (50) and the F(infinity) was about 11%. It
      seems likely that poly-L-Arg can be used to provide adequate nasal absorption of
      various protein drugs which have a molecular weight of about 20 kDa, thereby
      allowing the successful development of a variety of transnasal drug delivery
      systems.

PMID- 11532577
TI  - Biphasic drug release: the permeability of films containing pectin, chitosan and
      HPMC.
AB  - The permeabilities of mixed films of pectin/chitosan/HPMC have been studied to
      assess their value in producing a dosage form with biphasic drug release
      characteristics. The inclusion of chitosan enhanced the properties of the films,
      rendering them stable at all physiological pH values. Pectin/HPMC films were
      soluble at pH values above 3.0. All pectin/chitosan/HPMC films were permeable to
      a model drug, paracetamol. HPMC initially increased the permeability of the films
      and subsequently reduced it at higher concentrations. The minimum permeability
      was obtained at pH 3 and at an HPMC level of 5% where the potential for
      polyelectrolyte complex formation between pectin and chitosan exists. The
      permeabilities of the films increased when they were exposed to pectinolytic
      enzymes, a system designed to mimic conditions in the colon. The film formulation
      thus show the potential for biphasic delivery with an initial, controllable slow
      phase that can be manipulated by changes in the formulation followed by a faster
      phase under conditions pertaining in the colon.

PMID- 11532578
TI  - Selection of excipients for melt extrusion with two poorly water-soluble drugs by
      solubility parameter calculation and thermal analysis.
AB  - The aim of this study was to determine the miscibility of drug and excipient to
      predict if glass solutions are likely to form when drug and excipient are melt
      extruded. Two poorly water-soluble drugs, indomethacin and lacidipine, were
      selected along with 11 excipients (polymeric and non-polymeric). Estimation of
      drug/excipient miscibility was performed using a combination of the Hoy and
      Hoftzyer/Van Krevelen methods for Hansen solubility parameter calculation.
      Miscibility was experimentally investigated with differential scanning
      calorimetry (DSC) and hot stage microscopy (HSM). Studies were performed at
      drug/excipient ratios, 1:4, 1:1 and 4:1. Analysis of the glass transition
      temperature (T(g)) was performed by quench cooling drug/excipient melts in the
      DSC. Differences in the drug/excipient solubility parameters of <7.0 MPa(1/2)
      were predicted to indicate significant miscibility and, therefore, glass solution
      formation on melt extrusion. In comparison, differences of >10 MPa(1/2) were
      expected to indicate a lack of miscibility and not form glass solutions when melt
      extruded. Experimentally, miscibility was shown by changes in drug/excipient
      melting endotherms and confirmed by HSM investigations. Experimental results were
      in agreement with solubility parameter predictions. In addition, drug/excipient
      combinations predicted to be largely immiscible often exhibited more than one
      T(g) upon reheating in the DSC. Melt extrusion of miscible components resulted in
      amorphous solid solution formation, whereas extrusion of an "immiscible"
      component led to amorphous drug dispersed in crystalline excipient. In
      conclusion, combining calculation of Hansen solubility parameters with thermal
      analysis of drug/excipient miscibility can be successfully applied to predict
      formation of glass solutions with melt extrusion.

PMID- 11532579
TI  - Preparation and characterisation of a range of diclofenac salts.
AB  - Physicochemical properties of diclofenac salts prepared using eight different
      counterions and including five novel salts, obtained with the bases 2-amino-2
      methyl-1,3-propanediol, 2-amino-2-methylpropanol, tert-butylamine, benzylamine
      and deanol, were compared. Four of the bases used to prepare these salts were
      related in their chemical structure, differing only in the number of hydroxy
      groups. Characterisation techniques included X-ray diffraction, differential
      scanning calorimetry, thermogravimetric analysis, thermomicroscopy, Karl Fischer
      titration, FT-IR spectroscopy and elemental analysis. In the case of salts
      prepared from 2-amino-2-methylpropanol and benzylamine, two polymorphic forms of
      each salt were identified. For the 2-amino-2-methyl-1,3-propanediol salt, a
      pseudopolymorphic form was identified. The aqueous solubilities of the salts
      studied ranged from 3.95 mM (tris(hydroxymethyl)aminomethane salt) to 446 mM
      (deanol salt), corresponding to a 113-fold difference in solubility. The
      solubility of diclofenac deanol was higher than the solubilities for diclofenac
      salts reported earlier. Correlation was found between the inverse of the salt
      melting point and the logarithm of salt solubility. A log-log relationship was
      observed between salt solubility and hydrogen ion concentration in the salt
      solution. Relationships between the properties of the salt-forming agents and
      those of the resulting diclofenac salts were explored. Reasonable correlation was
      found between the free base melting point and the salt melting point.

PMID- 11532580
TI  - PLGA microparticles: possible vehicles for topical drug delivery.
AB  - Distribution of PLGA-microparticles in porcine skin, after its topical
      application, was studied in vitro using microparticles containing rhodamine as a
      fluorescent probe. PLGA-microparticles loaded with rhodamine were prepared using
      a solvent evaporation technique. Skin distribution of fluorescent microparticles
      was performed, by horizontal and vertical slicing of frozen skin. Fluorescence
      photomicrographs revealed that PLGA-microparticles could penetrate through the
      stratum corneum and reach the epidermis. However, permeation experiments showed
      that these microparticles were not able to reach the receptor compartment of the
      diffusion cells, even in a period of 24 h. The carriers described in this work
      could be used as vehicles for topical drug delivery, in order to obtain a
      sustained drug release into the skin, improving therapy by reduction of time
      intervals between doses.

PMID- 11532581
TI  - Thiolated polymers: synthesis and in vitro evaluation of polymer-cysteamine
      conjugates.
AB  - The purpose of the present study was to synthesize and characterize novel
      thiolated polymers. Mediated by a carbodiimide cysteamine was covalently linked
      to sodium carboxymethylcellulose (CMC) and polycarbophil (PCP). The resulting CMC
      cysteamine conjugates displayed 77.9+/-6.7 and 365.1+/-8.7 micromol thiol groups
      per gram of polymer, whereas the PCP-cysteamine conjugates showed 26.3+/-1.9 and
      122.7+/-3.8 micromol thiol groups per gram of polymer (mean+/-S.D.; n=3). In
      aqueous solutions above pH 5.0 both modified polymers were capable of forming
      inter- and/or intra-molecular disulfide bonds. The reaction velocity of this
      oxidation process was accelerated with a decrease in the proton concentration.
      The oxidation proceeded more rapidly within thiolated CMC than within thiolated
      PCP. Permeation studies carried out in Ussing-type chambers with freshly excised
      intestinal mucosa from guinea pigs utilizing sodium fluorescein as model drug for
      the paracellular uptake revealed an enhancement ratio (R=P(app)
      (conjugate)/P(app) (control)) of 1.15 and 1.41 (mean+/-S.D.; n=3) for the higher
      thiolated CMC-cysteamine (0.5%; m/v) and PCP-cysteamine conjugate (1.0%; m/v),
      respectively. The decrease in the transepithelial electrical resistance values
      was in good correlation with the enhancement ratios. Due to a high crosslinking
      tendency by the formation of disulfide bonds stabilizing drug carrier systems
      based on thiolated polymers and a permeation enhancing effect, CMC- and PCP
      cysteamine conjugates represent promising excipients for the development of novel
      drug delivery systems.

PMID- 11532582
TI  - Effect of sodium chloride on the gelation temperature, gel strength and
      bioadhesive force of poloxamer gels containing diclofenac sodium.
AB  - Liquid suppository systems composed of poloxamers and bioadhesive polymers were
      easy to administer to the anus and mucoadhesive to the rectal tissues without
      leakage after the dose. However, a liquid suppository system containing
      diclofenac sodium could not be developed using bioadhesive polymers, since the
      drug was precipitated in this preparation. To develop a liquid suppository system
      using sodium chloride instead of bioadhesive polymers, the physicochemical
      properties such as gelation temperature, gel strength and bioadhesive force of
      various formulations composed of diclofenac sodium, poloxamers and sodium
      chloride were investigated. The mixtures of P 407 (15%) and P 188 (15-20%)
      existed as a liquid at room temperature, but gelled at physiological temperature.
      Diclofenac sodium significantly increased the gelation temperature and weakened
      the gel strength and bioadhesive force, while sodium chloride did the opposite.
      Furthermore, the poloxamer gels with less than 1.0% of sodium chloride, in which
      the drug was not precipitated, were inserted into the rectum of rabbits without
      difficulty and leakage, and retained in the rectum of rats for at least 6 h. Our
      results suggested that a thermosensitive liquid suppository system with sodium
      chloride and poloxamers was a more physically stable and convenient rectal dosage
      form for diclofenac sodium.

PMID- 11532583
TI  - Quantitative structure-binding relationships (QSBR) and artificial neural
      networks: improved predictions in drug:cyclodextrin inclusion complexes.
AB  - The application of the principal neural network architecture, namely the
      multilayer perceptron (MLP), have been developed for obtaining sufficient
      quantitative structure-binding relationships (QSBR) with high accuracy. To this
      end a dataset of 17 barbiturates as guests complexing to alpha- and beta
      cyclodextrins was examined and the results compared to that of Lopata et al (J.
      Pharm. Sci., 74, (1995)) who studied the same problem using multiple regression
      analysis. A series of new and improved algorithms other than the "old fashion"
      and problematic steepest descent were examined for training the MLP networks. The
      proposed methods led to substantial gain in both the prediction ability and the
      computation speed of the resulting models. A specific ANN architecture (4-4-1)
      trained with the Levenberg-Marquardt algorithm diminished the number of outliers,
      during its implementation to unseen data (barbiturates), to zero.

PMID- 11532584
TI  - Preface: The road taken and to be traveled in improving end-of-life care.

PMID- 11532585
TI  - Evaluating the quality of dying and death.
AB  - We propose a model for evaluating the quality of dying and death based on
      concepts elicited from literature review, qualitative interviews with persons
      with and without chronic and terminal conditions, and consideration of desirable
      measurement properties. We define quality of dying and death as the degree to
      which a person's preferences for dying and the moment of death agree with
      observations of how the person actually died, as reported by others. Expected
      level of agreement is modified by circumstances surrounding death that may
      prevent following patient's prior preferences. Qualitative data analysis yielded
      six conceptual domains: symptoms and personal care, preparation for death, moment
      of death, family, treatment preferences, and whole person concerns. These domains
      encompass 31 aspects that can be rated by patients and others as to their
      importance prior to death and assessed by significant others or clinicians after
      death to assess the quality of the dying experience. The proposed model uses
      personal preferences about the dying experience to inform evaluation of this
      experience by others after death. This operational definition will guide
      validation of after-death reports of the quality of dying experience and
      evaluation of interventions to improve quality of end-of-life care.

PMID- 11532586
TI  - Preparing for the end of life: preferences of patients, families, physicians, and
      other care providers.
AB  - To examine patients', families', and health care providers' preferences regarding
      preparation for the end of life, attributes of preparation were generated in
      qualitative focus group discussions and subsequently tested for generalizability
      in a quantitative national survey. Respondents from all groups showed consensus
      on the importance of naming someone to make decisions, knowing what to expect
      about one's physical condition, having financial affairs in order, having
      treatment preferences in writing, and knowing that one's physician is comfortable
      talking about death and dying. Patients were more likely than physicians to want
      to plan funerals and know the timing of death and less likely than all other
      groups to want to discuss personal fears. Participants in care of dying patients
      agree overwhelmingly with the importance of preparation. However, significant
      barriers to preparation impede it from being a common part of clinical
      encounters. Further research and training are needed to ensure that the desire
      for greater preparation is translated into improved action toward preparation in
      medical practice.

PMID- 11532587
TI  - Patient-focused, family-centered end-of-life medical care: views of the
      guidelines and bereaved family members.
AB  - A fundamental barrier to improving the quality of medical care at the end of life
      is the lack of measurement tools. The Toolkit of Instruments to Measure End of
      Life Care (TIME) aims to fill that void by creating measurement tools that
      capture the patient and family perspective. To develop a conceptual model for a
      retrospective survey of bereaved family members that incorporates both
      professional and family perspectives on what constitutes good care at the end of
      life, a qualitative literature review of existing professional guidelines and six
      focus groups with bereaved family members from acute care hospitals (n = 2),
      nursing homes (n = 2), and hospice/VNA home health services (n = 2) was
      performed. The focus groups were held in Arizona, New York, and Massachusetts and
      included 42 bereaved family members/friends contacted 3-12 months from the time
      of patient's death. Domains of care that define quality end-of-life care were
      defined. Focus group participants defined high quality medical care as: 1)
      providing dying persons with desired physical comfort; 2) helping dying persons
      control decisions about medical care and daily routines; 3) relieving family
      members of the burden of being present at all times to advocate for their loved
      one; 4) educating family members so they felt confident to care for their loved
      ones at home; and 5) providing family members with emotional support both before
      and after the patient's death. The qualitative literature review yielded similar
      results, except that the professional guidelines did not mention the advocacy
      burden felt by families. These two sources provided the foundation for a
      conceptual model of patient-focused, family-centered medical care and a new tool
      for surveying bereaved family members. Views of bereaved family members' stories
      and professional guidelines help to identify key domains of quality of end-of
      life care. A new survey instrument provides a way to incorporate the perspectives
      of bereaved family members in measuring the quality of end-of-life care.

PMID- 11532588
TI  - Validation of Toolkit After-Death Bereaved Family Member Interview.
AB  - The purpose of this study was to examine the reliability and validity of the
      Toolkit After-Death Bereaved Family Member Interview to measure quality of care
      at the end of life from the unique perspective of family members. The survey
      included proposed problem scores (a count of the opportunity to improve the
      quality of care) and scales. Data were collected through a retrospective
      telephone survey with a family member who was interviewed between 3 and 6 months
      after the death of the patient. The setting was an outpatient hospice service, a
      consortium of nursing homes, and a hospital in New England. One hundred fifty-six
      family members from across these settings participated. The 8 proposed domains of
      care, as represented by problem scores or scales, were based on a conceptual
      model of patient-focused, family-centered medical care. The survey design
      emphasized face validity in order to provide actionable information to health
      care providers. A correlational and factor analysis was undertaken of the 8
      proposed problem scores or scales. Cronbach's alpha scores varied from 0.58 to
      0.87, with two problem scores (each of which had only 3 survey items) having a
      low alpha of 0.58. The mean item-to-total correlations for the other problem
      scores varied from 0.36 to 0.69, and the mean item-to-item correlations were
      between 0.32 and 0.70. The proposed problem scores or scales, with the exception
      of closure and advance care planning, demonstrated a moderate correlation (i.e.,
      from 0.44 to 0.52) with the overall rating of satisfaction (as measured by a five
      point, "excellent" to "poor" scale). Family members of persons who died with
      hospice service reported fewer problems in each of the six domains of medical
      care, gave a higher rating of the quality of care, and reported higher self
      efficacy in caring for their loved ones. These results indicate that 7 of the 8
      proposed problem scores or scales demonstrated psychometric properties that
      warrant further testing. The domain of closure demonstrated a poor correlation
      with overall satisfaction and requires further work. This survey could provide
      information to help guide quality improvement efforts to enhance the care of the
      dying.

PMID- 11532589
TI  - Improving end-of-life experience and care in the community: a conceptual
      framework.
AB  - End-of-life research and interventions have mostly focused on patients and
      family. There are compelling reasons for studying end-of-life experience and care
      from a community perspective. "Whole community" approaches to end-of-life care
      have been endorsed by the Institute of Medicine Committee on Care at End of Life.
      Building on the model developed by Stewart and colleagues, which integrates
      quality of life and quality of health indicators, a conceptual framework is
      presented that describes pertinent whole-community characteristics, structures,
      processes, and outcomes. The framework offers a map for whole-community research,
      intervention, and evaluation with the goal of changing the community culture
      related to life's end and thereby improving the quality of life for dying people
      and their families.

PMID- 11532590
TI  - Capacities and limitations of information systems as data sources on quality of
      care at the end of life.
AB  - Assessing quality of care at the end of life involves measurements in several
      domains-use of evidence-based guidelines, patient and family satisfaction,
      quality of life, and incidence of adverse events, among others. There are several
      different data sources from which to calculate quality measures. Each data source
      has a balance of strengths and weaknesses, and not all data sources are available
      in all possible settings of care. This paper describes how various data sources
      can be used to obtain the key data elements required for quality of care
      measures, as well as the challenges to linking data elements across sites and
      levels of care. There are some important quality domains (e.g., interpersonal and
      spiritual aspects of care) that are very difficult to assess using readily
      available data; primary data collection through interview and survey methods will
      be required to assess quality in these areas.

PMID- 11532591
TI  - After-death interviews with surrogates/bereaved family members: some issues of
      validity.
AB  - After-death interviews with bereaved respondents are an important tool in the
      repertoire of researchers evaluating the quality of end-of-life care or
      investigating the experiences of people at the end of life. Despite the
      importance of after-death interviews to our understanding of the last months of
      life, the validity of the information gathered has received little attention. In
      this article, we review some of the available information, drawing on evidence
      from cognitive psychology as well as from palliative care studies. Findings from
      cognitive psychology indicate that memory is a dynamic process, influenced by
      emotion state and the individual's perspective at the time of the event and at
      recall. Further research is therefore needed to understand better the
      circumstances, types of information and research questions for which bereaved
      relatives are valid surrogates for people who have died.

PMID- 11532592
TI  - Opioids and the treatment of chronic pain in a primary care sample.
AB  - Chronic pain is a widespread, difficult problem facing clinicians. This study
      assessed the current medical management of a general population of patients with
      chronic pain in 12 family medicine practices located throughout the state of
      Wisconsin. Medical record audits were conducted on a sample of 209 adults. Sixty
      seven percent were female with an average age of 53 years. The most common pain
      diagnoses included lumbar/low back (44%), joint disease/arthritis (33%), and
      headache/migraine (28%) pain. The most frequently prescribed opioids were
      oxycodone/acetaminophen (31%), morphine ERT (19%), Tylenol #3 (15%), and
      hydrocodone/acetaminophen (14%). Depression/affective disorders were reported in
      36% of the patient charts, anxiety/panic disorders (15%), drug abuse (6%), and
      alcohol abuse (3%). Written drug contracts were utilized by 42% (n = 31) of the
      practitioners, pain scales 25% (n = 29), and urine toxicology screens 8% (n = 6).
      This study suggests that primary care practitioners have unique opportunities to
      identify and successfully treat patients with chronic pain.

PMID- 11532593
TI  - Efficiency of searching the grey literature in palliative care.
AB  - A systematic review into palliative care team effectiveness was undertaken which
      has, inherent in its methodology, grey literature searching. Over 100 letters
      were written to a systematically chosen range of service providers,
      commissioners, and experts in combination with requests for information in six UK
      national cancer/palliative care organization newsletters. In addition, the System
      for Information on Grey Literature (SIGLE ) database was searched. As a result,
      25 document hard copies were received. The documents were, in all but one case
      (this one study was also highlighted by the SIGLE search), not relevant as they
      were predominated by annual reports, service descriptions, and needs assessments.
      In terms of obtaining unpublished studies for possible inclusion in the review,
      this comprehensive search was unsuccessful and, therefore, it would appear that
      grey literature searching is not a useful tool in palliative care systematic
      reviews.

PMID- 11532594
TI  - EMG-interference pattern analysis.
AB  - The EMG interference pattern, built up of single motor unit action potentials,
      may be analyzed subjectively, or objectively by computer aided, quantitative
      methods, like counting of zero-crossings, counting of spikes, amplitude
      measurements, integration of the area under the curve, decomposition techniques,
      power spectrum analysis and turn/amplitude analysis. Since the shape of the
      interference pattern of healthy muscles is dependent on age, sex, force, muscle,
      temperature, fatigue, fitness level, recording site and surrounding tissue,
      electrode type, sensitivity, filters, sampling frequency and threshold level, all
      methods of analyzing the IP have to be standardized. Quantitative methods of
      analyzing the EMG interference pattern may be used for monitoring botulinum toxin
      therapy of dystonia and spasticity, quantifying spontaneous activity, assessment
      of chronic muscle pain, neuro-urological and proctological function, and
      diagnosing neuromuscular disorders. For diagnostic purposes, the methods favored
      are those that use needle electrodes and do not require measurement or monitoring
      of muscle force. The most well-evaluated methods are those using turn/amplitude
      analysis, like the cloud methods and the peak-ratio analysis. Peak-ratio analysis
      has the advantage that reference limits are easy to obtain and that its utility
      is well established and confirmed by several investigations. Overall, automatic
      methods of EMG interference pattern analysis are powerful tools for diagnostic
      and non-diagnostic purposes.

PMID- 11532595
TI  - Trunk muscle coactivation in preparation for sudden load.
AB  - Biomechanical stability of the lumbar spine is an important factor in the
      etiology and control of low-back disorders. A principle component of
      biomechanical stability is the musculoskeletal stiffening generated by
      preparatory muscle coactivation. The goal of this investigation was to quantify
      preparatory behavior, evaluating trunk muscle activity immediately prior to
      sudden trunk flexion loading during static extension tasks compared to activity
      observed when subjects were informed no sudden load would occur. Coactive
      excitation was also examined as a function of fatigue and gender. Results
      demonstrated increased extensor muscle and flexor muscle coactivation following
      static fatiguing exertions, potentially compensating for reduced trunk stiffness.
      Female subjects produced greater flexor antagonism than in the males. No
      difference in the preparatory coactive muscle recruitment patterns were observed
      when subjects were expecting a sudden flexion load compared to recruitment
      patterns observed in similar static postures when subjects were informed no
      sudden load would be applied. This indicates the neuromuscular system relies
      greatly on response characteristics for the maintenance of stability in dynamic
      loading conditions.

PMID- 11532596
TI  - Discharge properties of human motor units during sustained contraction at low
      level force.
AB  - The characteristic of discharge behaviors of motor units (MUs) during low level
      contraction was investigated. The discharge of MUs in the m. vastus medialis was
      observed during the sustained contraction at 4 different levels below 10% MVC (2,
      4, 8 and 10% MVC) for 15 min. The spike interval of all observed MUs gradually
      elongated during an initial several minutes of the contraction and the
      characteristic discharge patterns following the elongation were observed. i.e.
      continuous discharge throughout the contraction (CONT), decruitment (D-N), and re
      recruitment following decruitment (D-REC). The relationship between recruitment
      threshold force (F(th)) and discharge pattern was not significant at 2% MVC but,
      at 10% MVC, there were significant differences in F(th) between D-N and CONT, and
      between D-REC and CONT MU populations. In pooled data, the MUs with the shorter
      mean spike interval at the beginning of the contraction (MSI(0), below 90 ms)
      tend to discharge continuously, but the MUs with longer MSI(0) showed various
      discharge patterns. In conclusion, during low level contraction MUs discharge
      characteristically, and the MU with high excitation levels tend to discharge
      continuously, but individual MU represents an intrinsic discharge pattern at not
      a high excitation level.

PMID- 11532597
TI  - Is lower limb muscle synchrony during landing affected by gender? Implications
      for variations in ACL injury rates.
AB  - This study examined whether lower limb muscle synchrony during abrupt landings
      was affected by gender, thereby predisposing females to a higher incidence of non
      contact anterior cruciate ligament (ACL) injuries than males. Seven males and 11
      females landed in single-limb stance on a force platform after receiving a chest
      height netball pass and decelerating abruptly. Ground reaction force and
      electromyographic data for rectus femoris, vastus lateralis, vastus medialis,
      semimembranosus (SM), biceps femoris, and gastrocnemius were sampled (1000 Hz)
      during landing. Subjects' sagittal plane motion was also filmed (200 Hz). Knee
      joint reaction forces and sagittal planar net moments of force were estimated
      using Newtonian equations of motion and inverse dynamics. Tibiofemoral shear
      forces (F(s)) were obtained and muscle bursts temporally analysed with respect to
      initial foot-ground contact (IC) and peak F(s) times. Males displayed
      significantly delayed SM onset relative to IC (113+/-46 ms) compared to females
      (173+/-54 ms; p=0.03), and significantly delayed SM peak activity relative to
      peak F(s) (54+/-27 ms) compared to females (77+/-15 ms; p=0.03). Delayed SM
      activity during landing was suggested to allow peak muscle activity to better
      coincide with high anterior F(s), thereby acting as an ACL synergist via
      increased joint compression and posterior tibial drawer. It was concluded that
      females displayed muscle synchrony less protective of the ACL than males,
      possibly increasing their susceptibility to non-contact ACL injuries.

PMID- 11532598
TI  - Spectral profile of superficial cervical muscles.
AB  - The objective of the study was to determine the median frequency (MF) and mean
      power frequency (MPF) of the stermodeidomastorial, splenius capitis and trapezius
      in progressively and linearly increasing isometric cervical flexion and
      extension. There is a dearth of data on spectral parameters of cervical muscles.
      Such data have been generated from 40 young adult subjects (21 male and 19
      female). The subjects were seated upright in an individually adjusted chair and
      stabilized with a 4-point Velcro restraint system to stabilize the torso. These
      subjects exerted isometric flexor and extensor forces in a random sequence on an
      instrumented resistance device (specifically designed for the study) in a gradual
      and linearly increasing manner with a visual feedback to their maximal voluntary
      contraction (MVC) within a 5 s period. Surface EMG was sampled from the
      sternocleidomastoid, the splenius capitis and the trapezius muscles bilaterally
      at 1 kHz. The EMG signals were subjected to Fast Fourier Transform (FFT)
      analysis. Spectral profiles of all muscles in the dimensions of frequency, power,
      and grade of contraction were plotted. The mean median frequency (MF), mean power
      frequency (MPF), peak power and total power were analyzed. In the
      sternocleidomastoid, and the splenius the MF increased with the grade of
      contraction, widening its bandwidth at higher grades. The trapezius maintained a
      narrow bandwidth and its MF declined with the grade of contraction.

PMID- 11532599
TI  - Neuromuscular fatigue during maximal concurrent hand grip and elbow flexion or
      extension.
AB  - The objective was to investigate muscle fatigue measuring changes in force output
      and force tremor and electromyographic activity (EMG) during two sustained
      maximal isometric contractions for 60s: (1) concurrent hand grip and elbow
      flexion (HG and EF); or (2) hand grip and elbow extension (HG and EE). Each force
      tremor amplitude was decomposed into four frequency bands (1-3, 4-10, 11-20, and
      21-50Hz). Surface EMGs were recorded from the flexor digitorum superficialis
      (FDS), extensor digitorum (ED), biceps brachii (BB) and lateral head of triceps
      brachii (TB). The HG and EF forces for the HG and EF and the HG force for the HG
      and EE declined rapidly, whereas the EE force remained almost constant near to
      the initial value for the first 40s and then declined. The decrease in EMG
      amplitude was observed not for the FDS muscle but for the ED muscle. The HG
      tremor amplitude for each frequency band showed similar decreasing rate, whereas
      the decreases in EF and EE tremor amplitudes for the lower band (below 10Hz) were
      slower than those for the higher band (above 11Hz). The neuromuscular mechanisms
      underlying muscle fatigue during sustained maximal concurrent contractions of
      hand grip and elbow flexion or extension are discussed.

PMID- 11532600
TI  - The effect of handgrip position on upper extremity neuromuscular responses to arm
      cranking exercise.
AB  - The purpose of this study was to determine if handgrip position during arm
      cranking exercise influences the neuromuscular activity of muscles biceps brachii
      (BB), lateral head of triceps brachii (TB), middle deltoid (DT), infraspinatus
      (IS) and brachioradialis (BR). Fifteen participants cranked an arm ergometer
      using three different handgrip positions (supinated, pronated, and neutral).
      Electromyographic (EMG) data were recorded from the aforementioned muscles, and
      relative duration of EMG activation and amplitude were quantified for the first
      and second 180 degrees of crank angle. EMG measures were analyzed with MANOVA and
      follow-up univariate procedures; alpha was set at 0.01. The relative durations of
      EMG activation did not differ between handgrip positions. Muscle IS exhibited 36%
      less amplitude in the supinated versus neutral handgrip position (second half
      cycle), and muscle BR displayed 63% greater amplitude across cycles in the
      neutral versus supinated and pronated handgrip positions. The greater BR activity
      displayed in the neutral handgrip position may reflect its anatomical advantage
      as an elbow flexor when the forearm is in neutral position. Muscle IS exhibited
      less activity in the supinated position and may be clinically relevant if it
      allows arm cranking to occur without subsequent shoulder pain, which is often the
      aim of shoulder rehabilitation.

PMID- 11532601
TI  - Mean power frequency and amplitude of the mechanomyographic and electromyographic
      signals during incremental cycle ergometry.
AB  - The purpose of this investigation was to determine the relationships for
      mechanomyographic (MMG) amplitude, MMG mean power frequency (MPF),
      electromyographic (EMG) amplitude, and EMG MPF versus power output during
      incremental cycle ergometry. Seventeen adults volunteered to perform an
      incremental test to exhaustion on a cycle ergometer. The test began at 50 W and
      the power output was increased by 30 W every 2 min until the subject could no
      longer maintain 70 rev min(-1). The MMG and EMG signals were recorded
      simultaneously from the vastus lateralis during the final 10 s of each power
      output and analyzed. MMG amplitude, MMG MPF, EMG amplitude, EMG MPF, and power
      output were normalized as a percentage of the maximal value from the cycle
      ergometer test. Polynomial regression analyses indicated that MMG amplitude
      increased (P<0.05) linearly across power output, but there was no change (P>0.05)
      in MMG MPF. EMG amplitude and MPF were fit best (P<0.05) with quadratic models.
      These results demonstrated dissociations among the time and frequency domains of
      MMG and EMG signals, which may provide information about motor control strategies
      during incremental cycle ergometry. The patterns for amplitude and frequency of
      the MMG signal may be useful for examining the relationship between motor-unit
      recruitment and firing rate during dynamic tasks.

PMID- 11532603
TI  - Composition, regulation, and function of the cytoskeleton in mammalian eggs and
      embryos.
AB  - The cytoskeleton of the mammalian egg and early embryo is highly unique when
      compared to the cytoskeleton of their somatic cell brethren. Although all three
      cytoskeletal systems, actin filaments, microtubules, and intermediate filaments,
      are present as early as the unfertilized egg; each system has adapted features
      that allow the egg and early embryo to meet the strict demands of the
      developmental process. The major demands placed upon eggs and embryos are
      developmental transitions (i.e., fertilization, compaction, blastocyst formation,
      germ layer formation and gastrulation), each of which must be traversed in order
      for the embryo to form a new individual. To successfully complete all of the
      necessary processes during early development, eggs and embryos must call upon
      many signal transduction mechanisms, cytoskeletal components, and genes that are
      both unique to embryogenesis and ubiquitous among many types of somatic cells. It
      is the goal of this review to provide some current details into the mechanisms
      that drive early development primarily focusing on the cytoskeletal components
      eggs and embryos have adapted to promote embryogenesis.

PMID- 11532602
TI  - Bromodomain motifs and "scaffolding"?
AB  - Bromodomain-containing multiprotein complexes share some of the properties of
      signal transduction scaffolds. Insights from MAP kinase signaling scaffolds, for
      example, may provide useful perspectives for future studies of bromodomain
      proteins. The regulatory processes of modification (phosphorylation, acetylation,
      ubiquitination), turnover, nuclear compartmentalization, feedback regulation and
      signaling pathway specificity are all likely to contribute to the mechanisms by
      which bromodomain-containing multiprotein complexes control transcription.

PMID- 11532604
TI  - Promoter targeting of chromatin-modifying complexes.
AB  - The action of multi-subunit complexes that are able to overcome the repressive
      effects of chromatin is an important step in the regulation of eukaryotic gene
      expression. Identification of complexes that modify the structure of chromatin to
      help factors access the underlying DNA has enhanced our understanding of how some
      genes are controlled. Histone acetyltransferases (HATs) and histone deacetylases
      (HDACs) represent one group of complexes that regulate the level of acetylation
      on the N-terminal tails of core histone proteins. The SWI/SNF complex is the
      prototype of a second group of complexes, which use the energy of ATP-hydrolysis
      to alter histone-DNA contacts, leading to changes in chromatin conformation.
      Genetic studies in yeast have revealed that some of these multi-subunit complexes
      interact in vivo to control transcription of a subset of genes. It has become
      apparent that some gene promoters require modifications by both types of
      complexes. An important question regarding these two types of complexes is how
      they are recruited to the promoters of genes that are dependent on their activity
      for their expression. This review will tie together many studies on promoter
      recruitment of both HATs and SWI/SNF. Emphasis will be placed on recent data that
      demonstrates functional interplay between these two types of chromatin-remodeling
      activities. In addition, this review summarizes recent data demonstrating the
      ability of repressors and corepressors to recruit histone deacetylase complexes.
      Interestingly, many subunits of chromatin-modifying complexes in humans have been
      implicated in the development of cancer. Thus, studying how these complexes work
      can help us better understand human diseases.

PMID- 11532605
TI  - Sensorimotor gating deficits and hypofrontality in schizophrenia.
AB  - Patients with schizophrenia exhibit (a) deficient sensorimotor gating as indexed
      by impaired prepulse inhibition (PPI) of the startle eyeblink reflex suggesting
      abnormal automatic information processing and (b) abnormal attentional modulation
      of PPI suggesting impaired controlled information processing. Here we test the
      hypothesis of deficient attentional modulation of PPI in schizophrenia as a
      defect in the interrelationship between frontal lobe functions of planning and
      executive action and posterior function of processing of sensory stimulation
      using positron emission tomography (PET). Consistent with the literature, our
      findings indicate that unmedicated schizophrenia patients exhibit lower
      frontal/occipital ratios (termed "hypofrontality") compared with healthy controls
      (n=15 in each group) during a standard tone-length-judgment (attention-to
      prepulse) task. Moreover, better attentional modulation of PPI was associated
      with higher frontal/occipital ratios in the control, but not the patient group.
      These findings extend animal models to humans by demonstrating the importance of
      frontal and occipital lobe coordination in the modulation of PPI.

PMID- 11532606
TI  - Prostate-specific genes: present status and future direction.
AB  - Prostate cancer (prostatic adenocarcinoma) is the second highest cause of cancer
      mortality in men and the benign prostatic hyperplasia (BPH) affects 80% of men by
      age 80. The current diagnosis of prostate cancer relies on the serum levels of
      the well-known molecule designated as prostate-specific antigen (PSA). PSA,
      however, has limited sensitivity and specificity in appropriately detecting the
      earlier stages of abnormal prostate growth. Additional molecules need to be
      identified that are prostate-specific and have better sensitivity and specificity
      that can detect prostate cancer and BPH at an earlier stage for clinical
      management. Presently, several laboratories are actively engaged in searching for
      such molecules. The aim of this article is to review the current status of
      various prostate genes reported in the literature that have been claimed to be
      prostate-specific with a function in normal and abnormal prostate growth and
      development. The long-term objective is to define the lacunae that exist in the
      literature in our search for an ideal antigen.

PMID- 11532607
TI  - Molecular genetic analysis of virulence in Mannheimia (pasteurella) haemolytica.
AB  - Mannheimia haemolytica (previously known as Pasteurella haemolytica) is a weakly
      hemolytic, gram-negative coccobacillus that is an opportunistic pathogen of
      cattle, sheep and other ruminants. In stressed, immunocompromised animals, the
      organism causes a fibrinous, necrotic pneumonia, commonly called "shipping
      fever". In the United States, economic losses due to shipping fever pneumonia
      surpass the combined cost of all other diseases of cattle. M. haemolytica, which
      is a member of the family Pasteurelleaceae, includes twelve serotypes (A1, A2, A5
      A9, A12-14, A16 and A17) based on capsular antigen typing. Worldwide, serotypes
      A1 and A2 predominate, though all serotypes can cause disease. Serotype A1 causes
      pasteurellosis in cattle and has been the subject extensive study, while serotype
      A2 causes disease in sheep and is less-well characterized. Potential virulence
      factors of M. haemolytica have been identified and characterized by gene cloning
      and DNA sequence analysis. These factors include a ruminant-specific leukotoxin,
      an anti-phagocytic capsule, lipopolysaccharide, iron-regulated outer membrane
      proteins, lipoproteins, a sialoglycoprotease, a neuraminidase and two potential
      immunoglobulin proteases. Unlike the well-characterized leukotoxin, little is
      known about the expression of these other virulence factors. Attempts to dissect
      the mechanisms of M. haemolytica pathogenesis have been hindered by the lack of a
      robust genetic system for mutation of the organism, though new tools for genetic
      manipulation of M. haemolytica have been developed. Expression plasmids and
      operon fusion plasmids have been created and a series of antibiotic resistance
      cassettes useful for site-specific recombination have been constructed. It is
      anticipated that use of these tools for gene expression and mutagenesis, in
      combination with the soon to be released genomic sequence of a serotype A1
      organism, will aid in understanding the molecular mechanisms of pathogenesis of
      M. haemolytica and will help to drive development of new vaccines to prevent
      shipping fever.

PMID- 11532608
TI  - The human mast cell: functions in physiology and disease.
AB  - Mast cells are multifunctional, tissue-dwelling cells capable of secreting a wide
      variety of mediators. They develop from bone marrow-derived progenitor cells,
      primed with stem cell factor (SCF), which mediates its actions by interacting
      with the SCF receptor or c-kit on the cell surface. Mast cells continue their
      maturation and differentiation in peripheral tissue, developing into two well
      described subsets of cells, MCT and MCTC cells, varying in content of tryptase
      and chymase as well as in immunobiology. Mast cells are activated by numerous
      stimuli, including antigen (acting via the high affinity IgE receptor, Fc?RI),
      superoxides, complement proteins, neuropeptides and lipoproteins resulting in
      activation and degranulation. Following activation, these cells express mediators
      such as histamine, leukotrienes and prostanoids, as well as proteases, and many
      cytokines and chemokines, pivotal to the genesis of an inflammatory response.
      Recent data suggests that mast cells may play an active role in such diverse
      diseases as atherosclerosis, malignancy, asthma, pulmonary fibrosis and
      arthritis. Mast cells directly interact with bacteria and appear to play a vital
      role in host defense against pathogens. Drugs, such as glucocorticoids,
      cyclosporine and cromolyn have been demonstrated to have inhibitory effects on
      mast cell degranulation or mediator release.

PMID- 11532609
TI  - Haemophilus influenzae - human specific bacteria.
AB  - Haemophilus influenzae is both a commensal and a pathogen specific to humans.
      Here we review this bacterium with special emphasis on characteristics that may
      be involved in virulence.

PMID- 11532610
TI  - Chromatin remodeling and initiation of DNA replication.
AB  - While much has been learned in recent years about the process of chromatin
      remodeling and its role in activation of transcription, relatively little has
      been reported on the role of chromatin remodeling in DNA replication. However, it
      is well established that transcription factors and chromatin structure play an
      important role in replication origin usage. Recent work has begun to indicate
      that chromatin remodeling factors are likely to play an important role in the
      regulation of replication origin usage. The results to date are most consistent
      with the role for chromatin remodeling factors in DNA replication as being
      indirect, and very similar to their role in transcription. The current evidence
      suggests that transcription factors bind to auxiliary sequences adjacent to
      replication origins and recruit chromatin remodeling factors to create either
      nucleosome-free regions or regions of specifically spaced nucleosomes. This
      results in activation of the nearby origin, presumably by making the origin
      region more accessible to replication factors. Until recently, there has been
      very little evidence of direct interactions between chromatin remodeling factors
      and the DNA replication machinery. Recent studies have provided data indicating
      that direct interactions may exist between chromatin remodeling factors and two
      cellular replication factors, the Origin Recognition Complex and Proliferating
      Cell Nuclear Antigen. However, since these replication factors are also involved
      in other nuclear processes, such as transcriptional silencing and DNA repair,
      respectively, further study is necessary to establish whether these direct
      interactions are also important for DNA replication.

PMID- 11532611
TI  - Abnormal phospholipid metabolism in schizophrenia: evidence from epidemiological
      findings, clinical observations, and preliminary clinical trials.
AB  - Both epidemiological findings and clinical observations and have shaped our
      thinking as regards to the neuropathology of schizophrenia. Epidemiological
      findings implicating environmental risk factors, including maternal dietary
      deficiency and urban birth place, suggest schizophrenia is a developmental
      disorder, whereas clinical observations gave rise to the "dopamine hypothesis."
      Epidemiological findings lead to complex multifactorial models, while clinical
      observations lead to more readily to testable, but not necessarily generalizable,
      hypotheses. Points where findings from these different approaches converge may
      provide us with new insights and points of departure. In this paper, clinical
      observations and epidemiological findings are presented which suggests that a
      subgroup of schizophrenics have abnormalities in phospholipid metabolism.
      Preliminary clinical trials involving administration of omega-3 fatty acids thus
      far appear to support this hypothesis.

PMID- 11532612
TI  - The link between chromatin structure, protein acetylation and cellular
      differentiation.
AB  - Chromatin remodeling and protein acetylation control gene expression and
      consequently regulate cellular growth and differentiation. Here we review the
      role of individual chromatin remodeling factors, acetyltransferases and
      deacetylases in the establishment and maintenance of different cell lineages and
      in the genesis of some human diseases.

PMID- 11532613
TI  - Electric activity of the rectosigmoid canal and its relation to rectal and
      sigmoid electric activity: an evidence of a sphincteric function of the
      rectosigmoid canal.
AB  - We have previously demonstrated that the rectosigmoid junction is more than a
      junction: it is a segment with a mean length of 2.8 cm which we termed the
      'rectosigmoid canal' (RSC). Our data support the existence of a physiologic and
      anatomic sphincter at the RSC which regulates the passage of stools from the
      sigmoid colon (SC) to the rectum (R). In view of its sphincteric action we
      investigated the hypothesis that the RSC has a higher electric activity than that
      of the SC and R. The tests were performed during repair of huge incisional hernia
      in 11 subjects (age 46.7(12.5 years; 8 women). The electric activity was recorded
      by means of 2 monopolar electrodes applied to each of the SC, RSC and R. The RSC
      was then anesthetized with xylocaine and the electric activity of SC, RSC and R
      was recorded after 10 minutes and one hour. The test was repeated using saline
      instead of xylocaine. The SC, RSC and R exhibited electric activity in the form
      of pacesetter potentials (PPs) and action potentials (APs). The PPs were
      monophasic in the SC and triphasic in the RSC and R. The frequency, amplitude and
      conduction velocity of the waves recorded from the RSC and R had higher readings
      (p<0.05) than those from the SC. The RSC and R showed a similar frequency and
      conduction velocity, but the RSC had a higher amplitude (p<0.05). Ten minutes
      after RSC anesthetization, electric waves were recorded from the SC but not from
      the RSC or R; electric activity returned one hour after anesthetization. Saline
      injection of the RSC did not affect the electric activity of the RSC, SC or R.
      The electric wave pattern and parameters of the RSC and R differed from those of
      the SC, suggesting that they are evoked by 2 different pacemakers. The similarity
      in pattern, frequency and conduction velocity of electric waves of RSC and R
      supposedly denotes that the rectal waves are a continuation of those of the RSC
      and that both are evoked by a single pacemaker located in the RSC. The higher
      amplitude of the RSC waves may be due to the thicker RSC musculosa in comparison
      to that of the SC and R and may by itself be an evidence of the sphincteric
      function of the RSC.

PMID- 11532614
TI  - New insight in cdk9 function: from Tat to MyoD.
AB  - Cdk9 is a serine-threonine cdc2-related kinase and its activity is not cell cycle
      regulated. Cdk9 function depends on its kinase activity and also on its
      regulatory units: the T-family cyclins and cyclin K. Recently, several studies
      confirmed the role of cdk9 in different cellular processes such as signal
      transduction, basal transcription, HIV-Tat- and MyoD-mediated transcription and
      differentiation. All the referred data strongly support the concept of a
      multifunctional protein kinase with specific cytoplasmic and nuclear functions.

PMID- 11532615
TI  - Contribution of HLA alleles in the regulation of antibody production in Lyme
      disease.
AB  - A small subset of patients infected with Borrelia burgdorferi (Bb) does not
      produce Bb specific antibody. Our research provides additional evidence of a
      genetic predisposition for seronegativity in some individuals with Lyme disease.
      Because human leukocyte antigen (HLA) class II, a heterodimeric glycoprotein,
      plays an essential role in the regulation of antibody production, we investigated
      the difference in HLA genes between seropositive and seronegative patients with
      Lyme disease (LD). Our results show that HLA-DR7 was associated with anti-Bb
      antibody production. Nine out of the 22 seropositive LD patients (40.9%) had HLA
      DRB1*0701, *0703, *0704 (HLA-DR7); only 1 out of the 18 seronegative LD patients
      (5.6%) had HLA-DR7 (odds ratio (OR)=11.8, P=0.0126). HLA-DRB1*01021 and HLA
      DRB1*0101, *0104, *0105 (HLA-DR1) contributed negatively to anti-Bb antibody
      production. Seven of 18 seronegative LD patients had HLA-DR1, only 1 of 22
      seropositive LD patients had HLA-DR1 (38.9% vs. 4.5%, OR=13.4, P=0.0138). These
      results suggest that the presence and or lack of production of specific antibody
      to Bb infection may be associated with particular HLA specificities of the Class
      II.

PMID- 11532616
TI  - Evidence-based approach to treatment of myelodysplastic syndromes.

PMID- 11532617
TI  - Clinical results in 2001 show high dose therapy and hematopoietic progenitor cell
      transplantation as a therapeutic option for breast cancer.

PMID- 11532618
TI  - Molecular therapy for multiple myeloma.
AB  - BACKGROUND AND OBJECTIVES: Several molecular and cytogenetic advances have
      suggested novel therapeutic strategies that could help reach an eventual cure for
      multiple myeloma (MM). EVIDENCE AND INFORMATION SOURCES: Identification of novel,
      "MM-specific" molecular targets should pave the way for drugs that can
      specifically attack the neoplastic cells while sparing the normal ones. Drugs
      that alter the marrow microenvironment--such as bisphosphonates, proteasome
      inhibitors (e.g. PS-341/LDP341), lactacystin or LLNV compounds--induce apoptosis
      or G1 growth arrest and alter the adhesion of MM cells to marrow stroma. These
      drugs that modified microenvironment have a more solid scientific basis and may
      therefore have more realistic implications in MM treatment. Of these, novel
      vascular endothelial growth factor (VEGF) inhibitors, such as SU5416 and SU6668,
      block tumor-cell adhesion and could disrupt MM cell proliferation. Similar
      tyrosine kinase inhibitors (TKI) such as fibroblast growth factor receptor (FGFR)
      inhibitors may serve when the FGFR3 gene is overexpressed due to the
      t(4;14)(p16.3;q32) and/or is activated by point mutations. In cases carrying the
      translocation and expressing the IgH/WHSC1-MMSET hybrid transcripts, histone
      deacetylase (HDAC) inhibitors could be useful, but their possible clinical use
      need to be supported by more biological studies. Tumor necrosis factor alpha
      related apoptosis-inducing ligand (TRAIL) induces apoptosis in MM cell lines and
      primary cells. The proliferative signaling pathway of FGFR3 is mediated by Ras
      (Ras-activating mutations are frequently found in MM), which presents a possible
      target for farnesyltransferase inhibitors (used alone or in association with IFN
      alpha). PERSPECTIVES: In several of these options, preclinical studies have
      proved encouraging, and clinical trials are now getting underway.

PMID- 11532619
TI  - Rapid mutational analysis of N-ras proto-oncogene in hematologic malignancies:
      study of 77 Greek patient.
AB  - BACKGROUND AND OBJECTIVES: N-ras mutations are the most commonly detected
      molecular abnormalities in hematologic malignancies, especially in those of
      myeloid origin. Different techniques have been used to detect N-ras mutations;
      however, most of them are either labor intensive or provide sequence data for
      only a limited number of codons. Consequently, study of the N-ras oncogene has
      not been convenient in every day clinical practice being restricted, as a rule,
      to retrospective analysis of patients. DESIGN AND METHODS: In this study we used
      a recently developed method that enables rapid and reliable detection of
      mutations at the cDNA level, namely, the non-isotopic RNase cleavage assay
      (NIRCA). Using this method we were able to screen the N-ras oncogene rapidly and
      determine the incidence and prognostic significance of N-ras mutations in 77
      Greek patients with acute leukemia, myelodysplastic syndromes and chronic
      myeloproliferative disorders, both at the presentation and during relapse or
      progression of the disease. RESULTS: Activating N-ras mutations were detected in
      7 patients and our results were confirmed by direct sequencing. Interestingly,
      two novel alterations were identified, a mutation at codon 8 (characterized by a
      substitution of valine by leucine) in a patient with chronic myeloid leukemia
      during hematologic relapse of the disease and a polymorphism at codon 92 (1002T-
      >C, without amino acid substitution) in a patient with chronic myelomonocytic
      leukemia. INTERPRETATION AND CONCLUSIONS: A rapid and easy protocol that allows
      the analyses of N-ras sequences has been developed. This reverse transcription
      polymerase chain reaction (RT-PCR)/NIRCA protocol can allow the study of this
      proto-oncogene in every day clinical practice, rapidly facilitating the
      validation of the diagnostic and prognostic value of N-ras mutational analyses in
      patients with hematologic malignancies.

PMID- 11532620
TI  - Spontaneous remission of aplastic anemia: a retrospective analysis.
AB  - BACKGROUND AND OBJECTIVES: Although acquired aplastic anemia is usually a chronic
      disorder, a small proportion of patients with aplastic anemia was reported to
      recover spontaneously without specific therapy such as allogeneic bone marrow
      transplantation or immunosuppressive treatment. We attempted to determine the
      rate of spontaneous remission in the patients with AA. DESIGN AND METHODS: We
      reviewed the medical records of adult patients (n=136) who were diagnosed as
      aplastic anemia at the Asan Medical Center from 1990 to 2000. The hematologic
      criteria of spontaneous remission were defined according to the proposed
      remission criteria of the SAA Working Party of the EBMT. RESULTS: Eighteen (13%)
      of 136 patients satisfied the criteria for spontaneous remission at median 14
      days (range, 4-332) from the diagnosis of aplastic anemia. In fifteen (83%) of 18
      patients, spontaneous remission occurred within 50 days. Spontaneous remission
      was complete in fourteen patients (78%). Only two patients relapsed at 208 and
      1,857 days after spontaneous remission, respectively. Multivariate logistic
      regression analysis showed that presence of infection at diagnosis (p = 0.017),
      drug as an etiology of aplastic anemia (p = 0.028), and serum albumin level less
      than 3.4 g/dL (p = 0.005) were independent predictive factors for spontaneous
      remission. INTERPRETATION AND CONCLUSIONS: Our study confirmed that a minority of
      patients with AA recovered spontaneously. Spontaneous remission was rapid and
      complete in most patients, and relapses were rarely observed. In most cases with
      spontaneous remission, aplastic anemia might be associated with external factors
      such as drug or infection.

PMID- 11532621
TI  - Flow cytometry in the bone marrow evaluation of follicular and diffuse large B
      cell lymphomas.
AB  - BACKGROUND AND OBJECTIVES: Bone marrow biopsies are routinely performed in the
      staging of patients with lymphoma. Despite the lack of evidence for its
      usefulness, many institutions include flow cytometry (FC) of bone-marrow
      aspirates in an attempt to increase sensitivity and specificity. The aim of this
      study is to evaluate the usefulness of FC for the assessment of bone-marrow
      involvement by lymphoma in follicular (FL) and diffuse large B-cell lymphomas
      (DLBCL). DESIGN AND METHODS: Seventy-nine bone marrow biopsies from 65 patients
      diagnosed with FL or DLBCL were examined to compare histology and FC for the
      assessment of bone-marrow involvement by lymphoma. RESULTS: Bone marrow histology
      showed involvement (BM+) in 16 cases (20.3%), lack of infiltration (BM(-)) in 52
      cases (65.8%) and undetermined or undiagnosed for involvement (BMu) in 11 cases
      (13.9%). FC was positive for involvement in 28 cases (35.4%) and negative in 51
      cases (64.6%). 65 cases (95%) showed concordance between the results of
      morphology and FC (BM(+)/FC(+) or BM(-)/FC(-)). No BM(+)/FC(-) cases were
      observed. 3 cases showed discrepant results (BM(-)/FC(+)). In these 3 cases the
      molecular studies (PCR) demonstrated clonal rearrangement of the heavy
      immunoglobulin chain (IgH) and/or bcl2-IgH in agreement with the flow results.
      Among the 11 cases with BMu, all but 2 were FC(+) and concordance with the PCR
      results was seen in 9 cases (81.9%). INTERPRETATION AND CONCLUSIONS: We conclude
      that FC is just as sensitive or perhaps slightly more sensitive than histology in
      the detection of bone marrow involvement in FL and DLBCL. FC studies may be
      warranted in those cases in which the morphology is not diagnosed. The clinical
      relevance of the small clonal B-cell population in patients without histologic
      bone marrow involvement (BM(-)/FC(+) cases) remains an open question.

PMID- 11532622
TI  - Risk-assessment in diffuse large cell lymphoma at first relapse. A study by the
      Italian Intergroup for Lymphomas.
AB  - BACKGROUND AND OBJECTIVES: Our aim was to identify risk factors in adults with
      diffuse large cell lymphoma at first relapse. DESIGN AND METHODS: We studied 474
      patients observed at 45 centers in Italy. Median time from diagnosis to relapse
      was 395 days, median age at relapse was 55 years and median follow-up from
      relapse was 3.3 years. Salvage therapy consisted of polychemotherapy in 79% of
      patients, monochemotherapy and/or radiotherapy and/or surgery alone in 16%, and
      palliative therapy in 5%. Salvage treatment was intensified with high-dose
      chemotherapy + stem cell transplant in 20% of patients. OS and PFS were compared
      by sex, International Prognostic Index at diagnosis, histology, B/T phenotype,
      initial treatment, salvage therapy, and features at relapse: time from diagnosis,
      LDH, stage, performance status and bone marrow involvement. Cox models, adjusted
      for salvage therapy, were performed with factors related to overall survival (OS)
      and progression-free survival (PFS). RESULTS: Overall response (complete +
      partial) was 63%, OS at 3 years 35% and PFS at 3 years 26%. Relapse within 12
      months from diagnosis, elevated serum lactic dehydrogenase (LDH), advanced stage
      and poor performance status were independent adverse factors for OS and PFS. The
      cumulative number of adverse factors is proposed as prognostic index for DLCL at
      first relapse since it identifies risk groups (p<0.0001) and has been validated
      (p=0.01). Moreover, it predicts OS and PFS in the selected group of patients with
      a responsive relapse (p<0.0001). INTERPRETATION AND CONCLUSION: Delay from
      initial diagnosis, LDH, stage and performance status at relapse should be
      balanced in comparative studies of salvage therapy of adults with DLCL. Patients
      with more than 2 adverse factors are one third of all cases and deserve more
      effective salvage treatments.

PMID- 11532624
TI  - Evaluation of thrombopoiesis kinetics by measurement of reticulated platelets and
      CD34(+) cell subsets in patients with solid tumors following high dose
      chemotherapy and autologous peripheral blood progenitor cell support.
AB  - BACKGROUND AND OBJECTIVES: The transplantation of mobilised peripheral progenitor
      cells has resulted in shortening of neutrophil and platelet engrafment times
      following high-dose chemotherapy. Since reticulated platelet percentage (PR%) has
      been established as a measure of bone marrow platelet production, we performed
      this type of analysis on the thrombopoietic compartment during transplant-related
      chemotherapy. DESIGN AND METHODS: Kinetics of thrombopoiesis of 19 patients with
      solid tumors undergoing a single or double autologous peripheral blood progenitor
      cell transplant was characterized by evaluating the level of RP. The correlation
      between CD34(+) cell subsets and the time of highest percentage of RP was also
      evaluated. RESULTS: The percentage of RP increases since day +8 after single
      transplant reaching the peak (3.4%) at day +10. In the group of patients
      receiving double transplant, the RP value of peak observed after second
      transplant is not significantly different from that one observed after the first
      transplant (3 vs 3.7%). In a subgroup of patients both the number of CD34(+)
      cells/Kg infused and the percentage of CD34(+) CD61(+) cell subsets correlate
      with the day of RP peak. INTERPRETATION AND CONCLUSIONS: These results suggest
      that RP measurement is an early indicator of engraftment. Additionally, the
      observation that RP percentage is high at the time of platelet transfusion in 13
      out of 20 cases of transfusions (the 7 cases with low RP value being transfused
      during the period of obligate thrombocytopenia) suggests that the evaluation of
      this parameter, together with the platelet count, can be used to monitor the need
      for platelet transfusion.

PMID- 11532623
TI  - Clinical activity and safety of combination immunotherapy with IFN-alpha 2a and
      Rituximab in patients with relapsed low grade non-Hodgkin's lymphoma.
AB  - BACKGROUND AND OBJECTIVES: To determine the clinical activity and safety of the
      combination immunotherapy of the chimeric anti-CD20 antibody, Rituximab, and
      Interferon (IFN)- alpha 2a DESIGN AND METHODS: Sixty-four patients with relapsed
      low-grade or follicular B-cell non Hodgkin's lymphoma received 4 infusion of
      Rituximab (375 mg/m(2) x dose) after priming and simultaneous treatment with IFN-
      alpha 2a. RESULTS: The overall response rate was 70% with 33% complete responses.
      Median for duration of response is 19 months, after a median follow-up of 22
      months. By univariate analysis none of the most common prognostic factors
      predicted for response to therapy. After treatment 10 patients become bcl-2
      negative in the bone marrow, but no correlation between molecular and clinical
      response was found. Fifty-three patients (83%) had drug related or unknown origin
      adverse events. The number of adverse events per patient varied from 1 to 21.
      Considering all 272 events, 231 (85%) were grade 1 or 2, 36 (13%) grade 3 and 5
      (2%) grade 4. Twenty-three patients required reduction in the dose and/or short
      discontinuation of IFN treatment, either during priming or subsequent treatment.
      The most frequent adverse events were leukopenia, fever, neutropenia, hypotension
      and thrombocytopenia. INTERPRETATION AND CONCLUSIONS: this report shows that
      combination immunotherapy Rituximab + IFN- alpha 2a is active and relatively well
      tolerated. The overall response rate of 70% and the median duration remission of
      19 months compare favorable with the results obtained with Rituximab alone in
      similar subset of patients. Randomized trials, investigating Rituximab versus
      combination immunotherapy are needed.

PMID- 11532625
TI  - Risk of thrombosis associated with oral contraceptives of women from 97 families
      with inherited thrombophilia: high risk of thrombosis in carriers of the G20210A
      mutation of the prothrombin gene.
AB  - BACKGROUND AND OBJECTIVES: Oral contraceptives (OC) and inherited thrombophilia
      are well-known risk factors associated with venous thromboembolism (VTE).
      However, there are only few studies on the risk of VTE in women with inherited
      thrombophilia who use oral contraceptives. DESIGN AND METHODS: We performed a
      retrospective family cohort study of 325 women belonging to 97 families with
      inherited thrombophilia, including antithrombin, protein S and C deficiencies,
      the factor V Leiden mutation (FVL) and the G20210A mutation of the prothrombin
      gene (PT20210A) to determine the risk of VTE associated with OC intake. RESULTS:
      For carriers of the PT20210A mutation, the risk of VTE in OC users was 3-fold
      higher (95% CI 1.3-6.8) than that in non-carriers. Carriers of FVL mutation
      taking OC showed an OR of 1.4 (95% CI 0.6-3.3), indicating a tendency to increase
      the risk of VTE. INTERPRETATION AND CONCLUSIONS: Because of the high prevalence
      of the PT20210A (6.5%) and FVL (2%) mutations in the general Spanish population
      and the increased risk of VTE associated with OC intake, genetic screening for
      these mutations should be considered in potential OC users belonging to families
      with thrombophilia.

PMID- 11532626
TI  - Plasma nitric oxide is associated with the occurrence of moderate to severe acute
      graft-versus-host disease in haemopoietic stem cell transplant recipients.
AB  - BACKGROUND AND OBJECTIVES: Nitric oxide (NO) has been implicated as one of the
      mediators of acute graft-versus-host disease (GVHD) but reports on its
      measurement during haemopoietic stem cell transplantation (HSCT) in human are
      scarce. The present study was conducted to measure the plasma NO in HSCT
      recipients in order to delineate its relationships with acute GVHD. DESIGN AND
      METHODS: Thirty-nine randomly selected patients undergoing HSCT were recruited.
      Thirty-one patients received allogeneic transplants (ALLO) from HLA-identical
      siblings (n=20), haploidentical parent (n=1) and matched unrelated donors (n=10).
      Eight patients received autologous (AUTO) HSCT. Plasma levels of nitrite/nitrate
      (NO(2)(-)/NO(3)(-)), the end-product of NO, were measured by chemiluminescence
      and the results were correlated with the occurrence and severity of acute GVHD.
      RESULTS: Baseline NO(2)(-)/NO(3)(-) levels before HSCT were similar in the ALLO
      and AUTO patients (17.4 vs 21.1 microL, p>0.05). Significant increases in plasma
      NO(2)(-)/NO(3)(-) (> 2 times the baseline level) were found in all 13 patients
      with acute GVHD > or = grade 2, in 15 out of 18 patients with acute GVHD grade <
      or = 1 and 3 out of 8 patients receiving autologous HSCT. The increase in NO(2)(
      )/NO(3)(-) among the three groups of patients was significantly different (135.5
      vs 56.3 vs 36.6 micromol/L, p < 0.001). The average NO production, calculated as
      the area under the curve, was also significantly differently among the three
      groups of patients (44.5 vs 30.0 vs 23.8 micromol/L, p < 0.001). INTERPRETATION
      AND CONCLUSIONS: Plasma NO in HSCT recipients is quantitatively associated with
      the occurrence of acute GVHD and its role remains to be determined.

PMID- 11532627
TI  - Chitotriosidase genotype and plasma activity in patients type 1 Gaucher's disease
      and their relatives (carriers and non carriers).
AB  - BACKGROUND AND OBJECTIVES: Chitinases are enzymes that hydolyze chitin and have
      been found in a wide variety of nonvertebrate species; recently an human analogue
      of chitinases, chitotriosidase (CT) has been identified. Extreme elevations of
      plasma CT activity are observed in patients with Gaucher disease (GD), being
      Gaucher cells the source of the CT. It has been reported a 24 bp duplication in
      CT gene that results an inactive protein. The carrier prevalence is high as 30 to
      40% and the CT activity is half that in wild individuals. However no systematic
      evaluation of plasma CT activity has been carried in GD patients taken into
      account status of allele defective for CT and dose in patients on enzyme
      replacement therapy (ERT). DESIGN AND METHODS: We had previously study 210
      subjects from 99 unrelated Spanish GD families; 121 were non-affected carriers
      and 89 were non-carriers to establish carrier prevalence of CT genotypes. Plasma
      CTactivity and CTgenotypes by PCR and gel electrophoresis have been measured in
      109 GD patients before treatment. We also evalued CT activity after ERT with
      alglucerase in 68 patients. RESULTS: Three patients had defective activities of
      CT. The carrier prevalence for 24 bp duplication was 35% and the allele frequency
      0.20. No correlation between CT activity and GBA genotype was detected and
      between CT activity and visceral or skeletal disease in GD patients. Untreated
      affected patients, non-carriers for the duplication, had higher CT activity than
      carriers (p<.0001). CT activity decreased dramatically during the first 12 months
      of ERT; even after 3 years of therapy a persistent fall of CT activity was
      observed. How ever within 3 years of treatment, a significant difference in the
      mean decrease of CT activity was present among the groups of patients on varying
      alglucerase doses (p<.01). After 12 months of ERT the activity of plasma CT
      decline in the same percentage in both groups: heterozygous for the carriers of
      24bp duplication and wild type, but thereafter CT activity decline more slowly in
      carriers than non carriers. INTERPRETATION AND CONCLUSIONS: The present data can
      be used as a reference to interpret the CT activity in GD patients with or
      without ERT, as well as to evaluate the doses response and can be used as a
      reference to interpret the CTactivity in carriers and non-carriers.

PMID- 11532629
TI  - Homozygous G6PD deficiency and propacetamol induced hemolysis.

PMID- 11532628
TI  - A rare case of compound heterozygosity for delta(+)27 and Hb Neapolis (Dhonburi)
      associated to an atypical beta-thalassemia phenotype.

PMID- 11532630
TI  - Decreased serum soluble macrophage colony stimulating factor receptor level in
      leukemia patients.

PMID- 11532631
TI  - Can minor bcr/abl translocation in acute leukemia be discriminated from major
      bcr/abl by extra-signal FISH analysis?

PMID- 11532632
TI  - Treatment of leukemia relapse after allogeneic hematopoietic stem cell
      transplantation by donor lymphocyte infusion and STI-571.

PMID- 11532633
TI  - CD69 expression in B-cell chronic lymphocytic leukemia: a new prognostic marker ?

PMID- 11532634
TI  - A novel pediatric case of cutaneous pre-B lymphoblastic lymphoma.

PMID- 11532636
TI  - Fatal cardiac toxicity in two patients receiving same-day administration of
      cyclophosphamide and cytarabine as conditioning for hematopoietic stem cell
      transplantation.

PMID- 11532635
TI  - Non-myeloablative conditioning regimen of fludarabine, busulfan, anti-thymocyte
      globulin, and methylprednisolone for allogeneic peripheral blood hematopoietic
      cell transplantation.

PMID- 11532637
TI  - A case of Behcet's disease complicated by visceral Leishmaniasis and
      myelodysplasia: clinical considerations.

PMID- 11532638
TI  - Bone remodeling in acute myeloid leukemia.

PMID- 11532639
TI  - Persistent polyclonal B-cell lymphocytosis in a middle-aged, smoking woman with
      typical morphologic and genetic hallmarks.

PMID- 11532640
TI  - Extensive life-threatening thrombosis in a patient with heparin-induced
      thrombocytopenia and factor V Leiden mutation.

PMID- 11532641
TI  - Anatomy, physiology, and pharmacology of the basal ganglia.
AB  - The basal ganglia consist of five interconnected nuclei in the basal forebrain
      that influence cortical control of voluntary movement. Synaptic information
      travels through the basal ganglia using distinct pathways from the input
      structure, the striatum, to the output nuclei, the substantia nigra pars
      reticulata and the globus pallidus internal segment. The activity of the striatal
      output pathways is influenced by glutamatergic input from the cerebral cortex,
      dopaminergic input from the substantia nigra pars compacta, and cholinergic
      interneurons. Since the basal ganglia output nuclei tonically inhibit the motor
      nuclei of the thalamus, the basal ganglia facilitate motor activity by
      disinhibiting the thalamus.

PMID- 11532642
TI  - Neurobehavioral aspects of movement disorders.
AB  - Cognitive, behavioral, affective, and psychiatric symptoms occur in almost all
      movement disorders. Diagnosis and management of movement disorders depends
      critically on an understanding of these neurobehavioral symptoms. This article
      reviews the neurobehavioral aspects of two representative movement disorders;
      Parkinson's disease and Huntington's disease.

PMID- 11532643
TI  - Movement disorders and normal aging.
AB  - As the population continues to age, it has become increasingly important for
      clinicians to recognize the clinical characteristics of normal aging. Impaired
      mobility is one of the most frequent effects of normal aging, and this
      necessitates a specific understanding of the effects of normal aging on the motor
      system. This article reviews the physiological basis and clinical manifestations
      of normal aging as related to movement disorders. The impact of normal aging on
      major hypokinetic and hyperkinetic movement disorders is also discussed.

PMID- 11532644
TI  - Parkinson's disease: clinical features, epidemiology and genetics.
AB  - Genetic and epidemiological studies are critical to understanding the etiology of
      Parkinson's Disease (PD), and may lead to rational treatments for the disease.
      This article reviews the clinical features, epidemiology and genetics of PD, with
      emphasis on insights from recent genetic and epidemiological studies.

PMID- 11532645
TI  - Parkinson's disease: medical and surgical treatment.
AB  - It has been over three decades since the introduction of L-dihydroxyphenylalanine
      or levodopa therapy for Parkinson's disease (PD). The early levodopa trials were
      driven by recognition of a profound cerebral dopamine deficiency state in this
      disorder. Whereas dopamine fails to cross the blood brain barrier and hence is
      ineffective as therapy, the amino acid precursor, dopa, is transported across
      this barrier and provides a substrate for dopamine synthesis. Levodopa is
      converted to dopamine within the brain by dopa decarboxylase, replenishing
      central dopamine stores and potentially reversing the motor symptoms of PD.

PMID- 11532646
TI  - Lumping and splitting the Parkinson Plus syndromes: dementia with Lewy bodies,
      multiple system atrophy, progressive supranuclear palsy, and cortical-basal
      ganglionic degeneration.
AB  - The atypical parkinsonian or Parkinson Plus syndromes are often difficult to
      differentiate from Parkinson's disease and each other. In this article, the
      clinicopathological characteristics of dementia with Lewy bodies, multiple system
      atrophy, progressive supranuclear palsy, and cortical-basal ganglionic
      degeneration are discussed. These disorders, although clinically distinct, may
      have more similarities than previously thought, based on modern
      immunocytochemical techniques and new genetic findings. These intriguing
      interconnections at a basic molecular level have provided the scientific
      rationale for lumping these diseases into two groups, the synucleinopathies and
      the tauopathies.

PMID- 11532647
TI  - Other Parkinson syndromes.
AB  - The etiology of parkinsonism is varied. Symptomatic parkinsonism is seen in the
      setting of genetic disorders, infectious processes, structural lesions, and as a
      result of concomitant medications. A thorough history and good examination will
      differentiate PD from the diverse group of conditions that can mimic it.

PMID- 11532648
TI  - Phenomenology and treatment of tremor disorders.
AB  - Tremor is classified according to anatomic distribution among body parts, and by
      frequency and amplitude during rest, postural maintenance, movement, intention,
      and the performance of specific tasks. Key historical features include age at
      onset, progression over time, family history, exacerbating and remitting factors
      and behaviors, response to alcohol and medications, and additional neurological
      signs and symptoms. Accurate diagnosis is a critical factor in predicting the
      natural history and response to treatment.

PMID- 11532649
TI  - Dystonia and its disorders.
AB  - Dystonia is a movement disorder characterized by sustained muscle contractions,
      frequently causing twisting and repetitive movements or abnormal postures. The
      term dystonia does not signify a single disease, but instead describes a symptom
      and sign that may be part of many disorders with a variety of causes. Dystonia
      may be classified by age of onset, distribution of symptoms, or by etiology. An
      increasing number of genetic forms of dystonia have been recognized and the
      findings have advanced knowledge of underlying neural mechanisms of pathogenesis.
      Options for treatment of dystonia include pharmacological therapy, botulinum
      toxin injection, or neurosurgical procedures.

PMID- 11532650
TI  - Chorea and its disorders.
AB  - Chorea (Greek for "dance") refers to irregular, rapid, flowing, non-stereotyped
      and random involuntary movements that often possess a writhing quality, referred
      to as choreoathetosis. When mild, it may be difficult to differentiate from
      restlessness. The movements can be strikingly asymmetric, as in hemichorea, or
      generalized. When chorea is proximal and of large amplitude, it is called
      ballism. Chorea is worsened by stress and anxiety and subsides during sleep.
      Movements can interfere with the completion of many daily activities, making
      fastening a button a substantial effort. Chorea often is incorporated into a
      purposeful activity in an attempt to disguise it. Motor impersistence is a common
      associated feature, demonstrated by varying intensity of grip strength
      (milkmaid's grasp) or by an inability to sustain eye closure or tongue
      protrusion.

PMID- 11532651
TI  - Myoclonus and its disorders.
AB  - This article defines myoclonus, describes the numerous causes of myoclonus, and
      summarizes various classification schemes. The electrodiagnostic characteristics
      and pathophysiology of this movement disorder are described. Treatment of the
      various forms of myoclonus is also discussed.

PMID- 11532652
TI  - Tics and its disorders.
AB  - Tourette syndrome (TS) is familial neuropsychiatric disorder that is
      characterized by motor and phonic tics that begin in childhood. Once thought of
      as a rare and debilitating disorder, in the last decade new scientific knowledge
      suggests that TS and related tic disorders are more common and less debilitating
      for the majority of individuals. Evidence points toward a spectrum of TS
      symptomatology that extends beyond the tics disorder to probably include
      obsessive-compulsive disorder, attention deficit hyperactivity disorder, and mood
      disorders. Tourette syndrome and its differential diagnosis are discussed in this
      article with a focus on new developments in classification, etiology,
      epidemiology, genetics, pathophysiology, and clinical management.

PMID- 11532653
TI  - Ataxia and hereditary disorders.
AB  - The last decade has seen great changes in the diagnosis of inherited ataxias.
      Previously mysterious diseases are now recognized to be caused by specific
      mutations for which genetic screening is readily available. In many cases, the
      discovery of the molecular basis has broadened the definition of possible
      clinical manifestations of particular inherited ataxias. The type of mutation
      underlying the more common forms of inherited ataxia-unstable trinucleotide
      repeat expansions-helps to explain some of the unusual features of these
      diseases. This article reviews recent genetic advances in ataxia. The aim is not
      to present an exhaustive summary but rather to provide guidance in evaluating
      ataxia, particularly with respect to recent molecular genetic findings.

PMID- 11532654
TI  - Pathophysiology of osteoporosis and fracture.
AB  - Bone is a vital, dynamic tissue that performs many functions, including a major
      role in serum homeostasis. A complex interplay of factors affects bone function
      and bone health. This article provides an overview of bone physiology and the
      pathophysiology of osteoporosis and fragility fracture. An understanding of the
      material presented here will provide a foundation to assess the bone health of
      individuals, to promote bone health, and to prevent fracture in patients of all
      ages.

PMID- 11532655
TI  - Assessment of risk factors for osteoporosis and fracture.
AB  - There are many factors that contribute to low bone mass and fracture. A careful
      health history is essential to identify both sets of risk factors. Identification
      of risk factors allows appropriate interventions to develop. Once a diagnosis has
      been established, laboratory and radiographic evaluation is needed to rule out
      secondary causes of osteoporosis. This article discusses risk factors for
      osteoporosis and fracture. It also discusses physical, laboratory, and
      radiographic evaluation.

PMID- 11532656
TI  - Diagnostic imaging and biochemical markers of bone turnover.
AB  - The diagnosis and monitoring of osteoporosis has evolved markedly in the last
      several decades. Nurses caring for patients with osteoporosis and those working
      in prevention settings must have an understanding of the tools currently
      available to diagnose the disease and measure treatment response. The purpose of
      this article is to describe current diagnostic imaging techniques and biochemical
      markers of bone turnover in osteoporosis.

PMID- 11532657
TI  - Role of calcium, vitamin D, and other essential nutrients in the prevention and
      treatment of osteoporosis.
AB  - Calcium is an essential nutrient for the prevention and treatment of
      osteoporosis. Despite universal recognition of its importance, most people still
      do not obtain recommended amounts. Recent additions to the treatment of
      osteoporosis with potent bone active drugs produce an even greater need for
      calcium and total nutrition for restoration of lost bone. Practitioners and
      patients need to emphasize and appreciate the role that calcium, vitamin D, and
      other nutrients play in the promotion of health and in the prevention and
      treatment of disease.

PMID- 11532658
TI  - Pharmacologic therapy for the treatment and prevention of osteoporosis.
AB  - Clinicians have an expanding menu of attractive pharmacologic options for the
      prevention and treatment of postmenopausal and age-related osteoporosis.
      Moreover, there exists excellent data from well-designed clinical trials
      documenting the effectiveness and tolerability of these therapies. Bone loss can
      be prevented in postmenopausal women of any age. Fracture risk can be reduced
      substantially in men and women with previous vertebral fractures or bone density
      values consistent with osteoporosis. It is clear that therapy is warranted in
      patients at high fracture risk. Important clinical challenges include devising
      effective strategies to identify those patients for whom treatment is indicated
      and to enhance both the accepting and long-term adherence to therapy by patients.

PMID- 11532659
TI  - Exercise in the prevention and treatment of osteoporosis: the role of physical
      therapy and nursing.
AB  - Exercise plays an important role in the prevention and treatment of osteoporosis.
      This article cites several scientific studies that support exercise as a means of
      increasing bone mass and strength for the prevention of osteoporosis. The
      ultimate goal of intervention for individuals with osteoporosis is fracture
      prevention. A comprehensive approach, including exercise, is outlined in this
      article, and the roles of the physical therapist and nurse are discussed.

PMID- 11532660
TI  - Corticosteroid-induced osteoporosis.
AB  - Long-term use of corticosteroids can lead to a change in bone turnover, and thus
      to a progressive decrease in bone mineral density, which increases the risk of
      fractures. Up to 50% of patients taking chronic corticosteroids sustain
      osteoporotic fractures. Although its actual incidence is unknown, corticosteroid
      induced osteoporosis is the most common form of drug-related osteoporosis. It is
      important that nurses become familiar with the diagnostic criteria for
      corticosteroid-induced osteoporosis and take the necessary steps toward
      prevention and treatment of this disease.

PMID- 11532661
TI  - Osteoporosis in men.
AB  - Osteoporosis in men is becoming a public health problem. The complications of the
      disease that represent fractures are associated with higher mortality and
      morbidity in men than in women. In the management of the disease, the nurse plays
      a major role in the education and management of men with osteoporosis.

PMID- 11532662
TI  - Quality of life in osteoporosis.
AB  - Osteoporotic hip, vertebral, and wrist fractures have dramatic effects on health
      related quality of life. Health status instruments can be used in evaluating
      quality of life deficits resulting from osteoporotic fractures. Although several
      lengthy health status instruments exist, shorter questionnaires must be developed
      to promote health status assessments in routine clinical practice. The authors
      have developed the disease-targeted, mini-Osteoporotic Quality of Life
      Questionnaire (OQLQ) to be used in clinical settings. The mini-OQLQ is extremely
      effective because it is self-administered and quickly completed. Information
      collected by health-related quality of life instruments may provide new insight
      as to how to improve quality of life for patients with fractures. Educational
      efforts are needed for health care professionals to increase the credibility of
      assessing health status in clinical practice.

PMID- 11532663
TI  - Case studies in osteoporosis management and prevention.
AB  - Although the goals of therapy in osteoporosis rely on tests to measure response
      to Pharmacologic therapy, the subsequent patient interview seems to yield the
      best results in evaluating the patient's response to treatment. Patients who are
      at fracture risk or who have significant disease present with uncertainty about
      their future quality of life. The health care provider can allay their fears and
      offer the best regimen to improve their condition.

PMID- 11532664
TI  - Current trends of surgical management of head and neck carcinomas.
AB  - Surgery and radiotherapy remain the mainstays of treatment for head and neck
      cancer. Surgical resection and reconstructive techniques are improving and offer
      the potential for organ and function preservation. This article gives an overview
      of carcinomas of the head and neck, salivary glands, and thyroid including
      epidemiology, staging, pathology, and standard treatment.

PMID- 11532665
TI  - Advances in surgical treatment of melanoma.
AB  - Malignant melanoma is fatal in one-fifth of the patients who are diagnosed with
      the disease. It is a solid tumor cancer that spreads primarily through lymph
      nodes, making it amenable to surgical treatment. Surgical interventions for
      melanoma that have developed over the years include diagnostic biopsy, wide
      excision, lymph node staging, and treatment of local and visceral metastases.
      Lymphatic mapping and sentinel lymph node biopsy are two important surgical
      approaches that are gaining favor over more traditional nodal staging. The use of
      reverse transcriptase-polymerase chain reaction (RT-PCR) to diagnose
      submicroscopic disease shows promise for staging patients at the earliest
      possible time. Multicenter, randomized clinical trials such as the Sunbelt
      Melanoma Trial are vital in answering the question of how best to treat early
      metastatic melanoma.

PMID- 11532666
TI  - Surgical therapies for lung carcinomas.
AB  - Lung cancer is the leading cause of cancer-related death for men and women in the
      world today. Surgical resection of early stage non-small cell lung cancer is the
      recommended treatment option and offers the patient the best chance for survival.
      Nurses are instrumental in lung cancer prevention, early detection, delivery of
      quality perioperative care, and maximizing long-term patient survival.

PMID- 11532667
TI  - Breast cancer: initial diagnosis and current treatment options.
AB  - Topics discussed in this article are breast cancer versus benign breast
      conditions, the importance of physical examination used in conjunction with
      screening mammography in the detection of abnormalities, imaging options,
      diagnosis, treatment options, and the importance of follow-up care.

PMID- 11532668
TI  - Evaluation and management of gastric adenocarcinoma.
AB  - This article reviews the epidemiology, cause, and current staging of gastric
      adenocarcinoma. An in-depth discussion regarding patient assessment and treatment
      options is presented. Advanced disease management and clinical trials are
      reviewed.

PMID- 11532669
TI  - Management of soft tissue sarcoma.
AB  - Sarcomas are rare and unusual neoplasms that can be found in any tissue and can
      have life-threatening outcomes. Caring for these patients can be a great
      challenge and requires a multidisciplinary team.

PMID- 11532670
TI  - Surgical approaches to pancreatic cancer.
AB  - Pancreatic cancer continues to be a significant health problem. Recent advances
      in medical technologies allow patients with pancreatic cancer to undergo
      diagnosis, staging, treatment, and palliation, and to minimize the traditional
      use of laparotomy as a method of obtaining information to facilitate treatment
      planning. Pancreatic surgery, which can impact duration and quality of life, can
      be reserved for that subset of patients likely to benefit from a surgical
      approach tailored to the specific needs of the individual patient.

PMID- 11532671
TI  - Current surgical management of colorectal cancer.
AB  - Colorectal cancer is the leading cause of death from gastrointestinal
      malignancies in the United States. Recent emphasis on screening of high-risk and
      no-risk individuals in addition to careful postoperative surveillance has
      decreased the incidence and improved the quality of life of survivors. Although
      multimodality approaches to treating colorectal cancer are favored, surgical
      resection continues to be the mainstay for a cure. This article reviews current
      surgical approaches and advances based on evidence for best practice.

PMID- 11532672
TI  - Hepatocellular carcinoma: surgical treatment options.
AB  - Hepatocellular carcinoma is one of the most common and lethal cancers worldwide.
      Survival rates generally are poor because of late diagnosis, tumor volume, and
      location. Early detection combined with surgical treatment advances, however, can
      provide longer disease-free survival.

PMID- 11532673
TI  - Recent surgical approaches to gynecologic oncology.
AB  - The development of gynecologic oncology as a specialty has contributed to the
      progress of the treatment and management of women with genital and reproductive
      cancers. The trend toward less aggressive and less invasive surgery has yielded
      an improved quality of life for women with gynecologic cancer. Multimodal
      interdisciplinary care is the principle and practice of gynecologic oncology.
      Prevention and screening have not always kept stride with the other advances in
      treatment, which include diagnostic imaging, laparoscopic surgery, chemotherapy,
      genetic susceptibility, and tumor marker assays. Educating patients and health
      care providers is the challenge in gynecologic oncology.

PMID- 11532674
TI  - The surgical oncology patient: provider obligations and legal rights.
AB  - The regulation of health care grows more complex and dynamic with each new law
      and policy implemented to create a general standard of care on which all patients
      can expect and rely. Most of these new laws and policies, however, are extensions
      of the following three basic tenants: the duty to treat, the consent to
      treatment, and the confidentiality of medical information. As these tenets
      evolve, they afford individuals certain rights before, during, and after they
      attain the status of patient.

PMID- 11532675
TI  - Quality of life in end-stage renal disease patients.
AB  - Health-related quality of life (QOL) refers to the measure of a patient's
      functioning, well-being, and general health perception in each of three domains:
      physical, psychological, and social. Along with survival and other types of
      clinical outcomes, patient QOL is an important indicator of the effectiveness of
      the medical care they receive. QOL of patients with end-stage renal disease is
      influenced by the disease itself and by the type of replacement therapy. Numerous
      studies have identified the effect of such factors as anemia, age, comorbidity,
      and depression on QOL. Most of these factors appear during the predialysis
      period, and the adequate management of some of them could influence patient
      outcomes. Among replacement therapies, transplantation appears to give the best
      QOL for large groups of patients. No conclusive data exist to prove differences
      in QOL between hemodialysis patients and peritoneal dialysis patients. In the
      case of elderly patients or those with a high degree of comorbidity, the best
      treatment option should be assessed in each individual case, taking all possible
      factors into account. Finally, it has been proven that physical and mental
      function are inversely correlated with the risk for hospitalization and
      mortality.

PMID- 11532676
TI  - Low Ca(2+) pump activity in diabetic nephropathy.
AB  - Elevated cell Na(+)-H(+) exchange (NHE) activity characterizes diabetic
      nephropathy (DN), but the mechanisms of this abnormality are unclear. Recent
      evidence suggests that NHE and the Ca(2+) pump share similar regulatory pathways,
      but whether abnormalities in Ca(2+) metabolism characterize DN is not known. We
      investigated Ca(2+) efflux rates, NHE activity, cytosolic Ca(2+) ([Ca(2+)](i))
      concentrations, and intracellular pH (pH(i)) in human skin fibroblasts from 20
      patients with type 1 (insulin-dependent) diabetes and nephropathy; 20 patients
      with diabetes with normoalbuminuria matched for age, sex, and duration of
      diabetes; and 10 individuals without diabetes. Ca(2+) pump-mediated Ca(2+) efflux
      was significantly lower in patients with nephropathy than in patients with
      normoalbuminuria and individuals without diabetes (0.074 +/- 0.01 versus 0.115 +/
      0.01 versus 0.131 +/- 0.02 nmol.mg(protein)(-1).min(-1); analysis of variance
      [ANOVA], P = 0.015). Elevated maximal velocity of the Na(+)-H(+) exchanger was
      confirmed in fibroblasts from patients with nephropathy (14.4 +/- 1.2 versus 7.1
      +/- 0.7 versus 8.0 +/- 1.2 mmol H(+).l cell(-1).min(-1); ANOVA, P < 0.0001). A
      reverse correlation between Ca(2+) pump activity and NHE rates could be shown.
      Adjustment for glycated hemoglobin and plasma lipid levels did not affect these
      findings. Finally, [Ca(2+)](i) concentrations and pH(i) were normal in all
      patients. Low Ca(2+) pump activity is a concomitant event of elevated NHE rates
      in DN; the molecular dysfunction(s) underlying these abnormalities remains to be
      established.

PMID- 11532677
TI  - Clinical features and genotype of adenine phosphoribosyltransferase deficiency in
      iceland.
AB  - The purpose of this study was to characterize the clinical, diagnostic, and
      prognostic features of adenine phosphoribosyltransferase (APRT) deficiency in
      Icelandic patients, as well as determine their genotype. Medical records of all
      known patients in Iceland were reviewed. Urinalysis and polymerase chain reaction
      based DNA mutation analysis were performed in all patients, siblings, and living
      parents of index cases. Twenty-three individuals homozygous for type I APRT
      deficiency were identified in 16 families from 1983 to 1998. There were 12 males
      and 11 females, and the median age at diagnosis was 37 years (range, 0.5 to 62
      years). Seventeen patients were index cases and 6 patients were diagnosed during
      screening of first-degree relatives. Eighteen patients had symptomatic disease,
      15 of whom experienced nephrolithiasis; 4 patients had mild to moderate renal
      insufficiency, 1 patient had advanced renal failure, and 1 patient died of uremic
      complications. Six patients experienced recurrent urinary tract infections and 3
      infants had a history of reddish-brown diaper stains. Five patients were
      asymptomatic; 3 of these patients were diagnosed during routine urinalysis and 2
      patients were identified during family screening. Urinary 2,8-dihydroxyadenine
      crystals were detected in all cases, except for the patient who died of end-stage
      renal failure. All 23 patients were homozygous for the same mutation (D65V) in
      the APRT gene. Allopurinol therapy successfully prevented further stone formation
      and significantly improved renal function in most patients with renal
      insufficiency. Our results suggest that APRT deficiency may be more common than
      previously recognized and can lead to severe renal failure if left untreated.

PMID- 11532678
TI  - Analysis of human urine protein biomarkers via biomolecular interaction analysis
      mass spectrometry.
AB  - Biomolecular interaction analysis mass spectrometry (BIA/MS) is a two-dimensional
      chip-based analytical technique geared toward quantitative and qualitative
      analysis of small volumes of biological samples. Interactions between surface
      immobilized ligands and solute-borne analytes are quantitatively viewed in real
      time through surface plasmon resonance sensing, followed by qualitative matrix
      assisted laser desorption/ionization time-of-flight MS analysis of the analyte(s)
      affinity-retained on the sensor surface. In this work, BIA/MS was used in the
      detection of a number of protein biomarkers from human urine. Small volumes of
      human urine were analyzed for cystatin C, beta(2)-microglobulin, urinary protein
      1, and retinol-binding protein (RBP). Multiaffinity sensor surfaces were created
      to simultaneously and rapidly detect all four proteins in a single BIA/MS
      analysis on a two-flow cell sensor chip configuration. Furthermore, RBP was
      analyzed separately from both urine and plasma samples. Results indicate that
      BIA/MS can be used successfully in rapid screening of a number of urinary
      proteins indicated as putative biological markers for renal dysfunction.

PMID- 11532679
TI  - Prognostic factors for persistent distal renal tubular acidosis after surgery for
      posterior urethral valve.
AB  - Risk factors, including age at presentation, age at surgery, time between
      presentation and surgery, urodynamic abnormalities, and vesicoureteric reflux,
      were prospectively studied for the development of distal renal tubular acidosis
      (DRTA) before surgery and persistent DRTA after surgery in 24 boys with posterior
      urethral valve (PUV) with normal serum creatinine levels. DRTA was persistent in
      11 of 17 boys (65%) at the end of follow-up after intervention. For the
      development of DRTA before surgery, only a longer time between presentation and
      surgery (intervening period) turned out to be a significant risk factor on
      multivariate analysis (beta = -0.13; P = 0.04). Boys with persistent DRTA after
      surgery had older age at presentation (P = 0.03), older age at surgery (P =
      0.001), a longer intervening period (P = 0.0007), and bilateral or severe
      unilateral reflux (P = 0.04) before surgery. On univariate logistic regression,
      age at surgery (beta = -0.07; P = 0.04) and intervening period (beta = -0.13; P =
      0.02) were found to be significant risk factors for persistent DRTA, but on
      multivariate analysis, only intervening period was found to be significant (beta
      = -0.13; P = 0.02). A delay in intervention after noticing voiding symptoms can
      predict a high incidence of DRTA before intervention and persistent DRTA after
      surgery in boys with PUV.

PMID- 11532680
TI  - Timing of nephrologist referral and arteriovenous access use: the CHOICE Study.
AB  - Recent clinical practice guidelines recommend the creation of an arteriovenous
      (AV) vascular access (ie, native fistula or synthetic graft) before the start of
      chronic hemodialysis therapy to prevent the need for complication-prone dialysis
      catheters. We report on the association of referral to a nephrologist with
      duration of dialysis-catheter use and type of vascular access used in the first 6
      months of hemodialysis therapy. The study population is a representative cohort
      of 356 patients with questionnaire, laboratory, and medical record data collected
      as part of the Choices for Healthy Outcomes in Caring for End-Stage Renal Disease
      Center Study. Patients who reported being seen by a nephrologist at least 1 month
      before starting hemodialysis therapy (75%) were more likely than those referred
      later to use an AV access at initiation (39% versus 10%; P < 0.001) and 6 months
      after starting hemodialysis therapy (74% versus 56%; P < 0.01). Patients referred
      within 1 month of initiating hemodialysis therapy used a dialysis catheter for a
      median of 202 days compared with 64, 67, and 19 days for patients referred 1 to
      4, 4 to 12, and greater than 12 months before initiating hemodialysis therapy,
      respectively (P trend < 0.001). Patients referred at least 4 months before
      initiating hemodialysis therapy were more likely than patients referred later to
      use an AV fistula, rather than a synthetic graft, as their first AV access (45%
      versus 31%; P < 0.01). These associations remained after adjustment for age, sex,
      race, marital status, education, insurance coverage, comorbid disease status,
      albumin level, body mass index, and underlying renal diagnosis. These data show
      that late referral to a nephrologist substantially increases the likelihood of
      dialysis-catheter use at the initiation of hemodialysis therapy and is associated
      with prolonged catheter use. Regardless of the time of referral, only a minority
      of patients used an AV access at the initiation of treatment, and greater than
      25% had not used an AV access 6 months after initiation. Thus, further efforts to
      improve both referral patterns and preparation for dialysis after referral are
      needed.

PMID- 11532681
TI  - Heart failure, aging, and renal synthesis of dopamine.
AB  - The present study evaluates renal dopaminergic activity in 23 patients with heart
      failure (HF), 10 age-matched controls, and 10 young subjects during normal-salt
      (NS) intake and after 8 days of low-salt (LS) intake (patients with HF and age
      matched controls only). LS intake produced a marked reduction in urine volume in
      patients with HF but failed to affect urine volume in age-matched controls.
      Urinary sodium and fractional excretion of sodium were markedly reduced by LS
      intake in patients with HF and age-matched controls. Daily urinary excretion of L
      3,4-dihydroxyphenylalanine (L-dopa) and dopamine was lower in patients with HF
      than in age-matched controls. LS intake failed to alter L-dopa and dopamine
      urinary excretion in control subjects. In patients with HF, LS intake produced a
      significant decrease in urinary L-dopa excretion, but failed to alter the urinary
      excretion of dopamine. No significant differences were observed in urinary L
      dopa, dopamine, and dopamine metabolite levels between aged controls and young
      healthy subjects. Urinary dopamine-L-dopa ratios in patients with HF on LS intake
      (24.5 +/- 7.1) were significantly greater than those with NS intake (11.6 +/-
      1.3). Urinary dopamine-L-dopa ratios in old control subjects (LS, 9.7 +/- 1.3;
      NS, 9.3 +/- 1.1) did not differ from those in young healthy subjects (9.2 +/-
      0.8). LS intake produced a marked increase in plasma aldosterone levels in both
      patients with HF (84.6 +/- 14.4 to 148.2 +/- 20.4 pg/mL; P = 0.0008) and controls
      (102.1 +/- 13.4 to 151.6 +/- 15.7 pg/mL; P < 0.04). Plasma norepinephrine levels
      were not significantly affected by LS intake in controls (5.1 +/- 1.62 to 6.3 +/-
      1.6 pmol/mL; P = 0.22), but were significantly increased in patients with HF (5.8
      +/- 0.8 to 7.1 +/- 0.9 pmol/mL; P = 0.04). In conclusion, patients with HF are
      endowed with an enhanced ability to take up (or decarboxylate) filtered L-dopa,
      which might counterbalance the reduced renal delivery of L-dopa, contributing to
      a relative preservation of dopamine synthesis. This may result as a compensatory
      mechanism, activated by stimuli leading to sodium reabsorption. Age seems to have
      no influence on renal dopamine production.

PMID- 11532682
TI  - Plasma levels and metabolism of AcSDKP in patients with chronic renal failure:
      relationship with erythropoietin requirements.
AB  - N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) is a physiological inhibitor of
      hematopoiesis that is maintained at stable levels in normal plasma. Its
      degradation in vivo and in vitro by angiotensin-converting enzyme (ACE) accounts
      for the high plasma concentrations of AcSDKP in patients treated with ACE
      inhibitors. Because ACE inhibitors can induce anemia in some patients, we
      measured plasma AcSDKP concentrations in 176 patients with chronic renal failure:
      120 hemodialysis (HD) and 56 nondialysis (nD) patients, 39 of whom were
      administered ACE inhibitors. We studied the relationships between AcSDKP levels,
      hematologic parameters, and recombinant human erythropoietin (rHuEPO)
      requirements in these patients. AcSDKP levels were significantly greater in HD
      (10.3 +/- 3.9 pmol/mL) and nD (3.1 +/- 1.8 pmol/mL) patients not administered ACE
      inhibitors than controls (1.8 +/- 0.2 pmol/mL). In all patients, treatment with
      ACE inhibitors significantly increased these levels fourfold. HD sessions
      significantly decreased AcSDKP concentrations by 66% and reduced the predialysis
      in vitro half-life of AcSDKP (270 +/- 109 minutes) to values (182 +/- 67 minutes)
      not significantly different from those of controls or nD patients. Most HD
      patients treated with ACE inhibitors had AcSDKP levels greater than 24 pmol/mL
      (the greatest concentration found in other nD and HD patients). Only in this
      group of patients did weekly doses of rHuEPO correlate with AcSDKP levels. Our
      results show that renal function is essential to maintain stable AcSDKP plasma
      levels, and at high levels, AcSDKP acts as a uremic toxin causing partial
      resistance to erythropoietin and inhibiting erythropoiesis.

PMID- 11532683
TI  - Gender modulates responsiveness to recombinant erythropoietin.
AB  - Several investigators reported that individuals with diabetes and women on
      hemodialysis treated with recombinant erythropoietin (EPO) attained lower
      hematocrits than individuals without diabetes and men. It is unclear whether
      these observed differences in achieved hematocrits are caused by inherent
      biological differences in responsiveness to EPO or undetected differences in
      modifiable factors that affect response to EPO. Also potentially modulating
      response to EPO is diurnal variation in the bioavailability of serum iron. To
      address these issues, we studied 309 patients undergoing hemodialysis in two
      large facilities in New York City. Retrospective data collected monthly for 3
      months included patients' hematocrit, dose of EPO, urea reduction ratio (URR),
      total amount of intravenous iron administered, serum albumin concentration,
      transferrin saturation, and time of day patient underwent dialysis. The 309 study
      subjects (165 women, 144 men) included 207 blacks (67%), 74 Hispanics (24%), 23
      whites (7%), and 5 Asians (2%) with a mean age of 55.4 +/- 15.6 (SD) years.
      Despite a greater mean URR (74% +/- 6.4% versus 71% +/- 6%; P = 0.001) and a 39%
      greater dose of EPO (97 +/- 65 versus 59 +/- 53 U/kg; P = 0.001), women (36% +/-
      3.5%) had hematocrits equivalent with men (36.5% +/- 3.7%; P = not significant
      [NS]). There was no difference in the amount of intravenous iron administered to
      men (375 +/- 389 mg) and women (377 +/- 413 mg; P = NS). Diabetes mellitus (P =
      0.48) did not significantly affect the odds of attaining a hematocrit greater
      than 33% after adjustment for URR, EPO dose, and amount of intravenous iron
      administered. The time of day a patient underwent dialysis (P = 0.93) had no
      effect on their response to EPO. We conclude that gender, but not diabetes status
      or time of dialysis, modulates response to EPO in hemodialysis patients.

PMID- 11532684
TI  - Cocaine use, hypertension, and end-stage renal disease.
AB  - Cocaine use has been associated with both acute renal failure and hypertension
      (HTN), but only recently have data suggested it may lead to a chronic insidious
      form of renal failure. We designed a cross-sectional study to compare the
      association of cocaine use in hemodialysis patients with and without a diagnosis
      of HTN-related end-stage renal disease (HTN-ESRD). Two hundred one black patients
      from two outpatient hemodialysis units in an urban community were evaluated.
      There were 193 eligible patients, 106 men and 87 women, aged 49.28 +/- 14.4
      years. A history of significant cocaine use before dialysis was reported by 55 of
      193 subjects (28.5%). A diagnosis of HTN-ESRD was reported in 49 of 55 cocaine
      users (89.1%) compared with 64 of 138 nonusers (46.38%; odds ratio, 9.44; 95%
      confidence interval, 3.79 to 23.49; P < 0.0005). Of the 113 subjects with HTN
      ESRD, 49 subjects (43.4%) had a history of cocaine abuse, either alone or in
      combination with other drugs. Subjects with HTN-ESRD with cocaine use were
      younger than those without cocaine use (40.7 +/- 9.0 versus 53.8 +/-15.3 years; P
      < 0.0005) and had a shorter reported duration of HTN (5.3 +/- 5.4 versus 12.7 +/-
      9.8 years; P < 0.0005, adjusted for age and sex). In our urban dialysis
      population, a clinical diagnosis of HTN-ESRD was strongly associated with a
      history of cocaine use and earlier onset of ESRD. Cocaine should be considered as
      a cause of ESRD in patients without a clear cause of renal failure.

PMID- 11532685
TI  - Mitochondrial DNA mutations in black Americans with hypertension-associated end
      stage renal disease.
AB  - For the majority of hypertensive cases, no gene or combination of genes and
      environmental factors clearly leading to hypertension has been identified.
      Studies to identify "hypertension" genes have focused on the assessment of
      markers and candidate genes in the nuclear genome. In this study, we have chosen
      to assess the mitochondrial genome as a site of mutations possibly contributing
      to susceptibility to hypertension in black Americans who have progressed to end
      stage renal disease (H-ESRD). The mitochondrial genomes of 58 H-ESRD and 58
      normotensive individuals were systematically analyzed by means of a high
      resolution restriction analysis. After stratification by the presence or absence
      of an African continent-specific HpaI site gain at bp 3,592, differences in the
      frequencies of mitochondrial DNA (mtDNA) restriction variants in both groups were
      examined by chi-square analyses. A total of six variants was identified with
      significant differences in one or both cohorts. An A10398G DdeI mutation in the
      ND3 gene was significantly increased in the H-ESRD cohort (H-ESRD, P = 0.048;
      normotensives, P = 0.20), as was an HaeIII T6620C/G6260A double mutation in the
      CO1 gene (H-ESRD, P = 0.05; normotensives, P = 0.48). The remaining four variants
      were a G2758A mutation in the 16SrRNA gene (identified by RsaI), T10810C in the
      ND4 gene (identified by HinfI), a G7028A/T7055C double mutation in the CO1 gene
      (identified by AluI), and finally, a A10086G mutation in the ND3 gene (identified
      by TaqI; also causing an Asn-->Asp amino acid change). The RsaI and HinfI
      variants were in strong linkage disequilibrium with the HpaI site and not
      amenable to further analysis. After correction of all P values for multiple
      comparisons, the ND3 A10086G (Asn-->Asp) mutation shown by TaqI remained
      statistically significant (P = 0.0036) in the H-ESRD cohort, not in the
      normotensive cohort. To the best of our knowledge, this is the first report of an
      increased prevalence of mitochondrial gene variants in hypertensive individuals.
      In addition, we have identified single-nucleotide polymorphisms in flanking
      regions of these genes. Although replication and further assessment are
      necessary, the current results support our hypothesis that mtDNA may account for
      a portion of hypertensive cases in black Americans with ESRD.

PMID- 11532686
TI  - Epidemiological evaluation of known and suspected cardiovascular risk factors in
      chronic renal impairment.
AB  - Patients with chronic renal impairment (CRI) are at greatly increased risk for
      premature vascular disease; however, little is known about its evolution. This
      paper describes a cohort of patients with CRI and reports study design, baseline
      demographic and biochemical data, and comparisons with two contemporaneous age-
      and sex-matched control groups, one with established coronary artery disease and
      the other without overt vascular disease. Among 369 individuals (median age, 63
      years; range, 18 to 88 years; 67% men) with CRI, 34% had a history of vascular
      disease and 21% had electrocardiographic left ventricular hypertrophy (LVH). Even
      in those with mild renal impairment (serum creatinine < 2.1 mg/dL), approximately
      one third had vascular disease and 12% had LVH. A history of hypertension was
      present in 76% of the CRI group, but as compared with controls, systolic and
      diastolic blood pressures were not elevated. Low-density lipoprotein (LDL)
      cholesterol concentration also was not elevated, but CRI was associated with
      elevated serum triglyceride and plasma homocysteine levels and reduced high
      density lipoprotein (HDL) cholesterol, hemoglobin, and serum albumin
      concentrations. Across the spectrum of CRI, more severe renal dysfunction was
      associated with lower levels of diastolic blood pressure, LDL and HDL
      cholesterol, albumin, and hemoglobin, but increased levels of plasma
      homocysteine. This cross-sectional analysis shows that vascular disease is common
      in individuals with mild CRI attending a nephrology program and also suggests
      trends in the levels of a number of potential vascular risk factors with respect
      to severity of renal dysfunction. These results will be further quantified in a
      prospective biennial follow-up.

PMID- 11532688
TI  - Successful use of Tesio catheters in pediatric patients receiving chronic
      hemodialysis.
AB  - Semipermanent venous catheters remain the most commonly used access for chronic
      hemodialysis (HD) in pediatric patients. The recent availability of Tesio
      catheters in 7 and 10 F has expanded available HD catheter options for children
      and adolescents. We report our experience with Tesio catheter survival,
      complications, and effect on dialysis adequacy in comparison to standard dual
      lumen (DL) catheters in our pediatric HD patients. Demographic data were similar
      between the two groups. Overall actuarial survival was significantly longer for
      Tesio versus DL catheters (46% versus 0% at 1 year; P = 0.003). A comparison of
      smaller catheters (7 F Tesio catheter, 8 or 10 F DL catheter) showed that smaller
      Tesio catheters had a significantly longer survival (median survival, 244 versus
      13 catheter-days; P < 0.01). Tesio 10 F catheters also survived significantly
      longer than the larger 11.5 and 12 F DL catheters (P < 0.02). Catheter sepsis
      occurred less frequently with Tesio catheters (one episode/20 catheter-months)
      than DL catheters (one episode/5 catheter-months) despite the longer duration of
      Tesio catheters. Adequate dialysis (single-pool Kt/V > 1.2) was delivered with
      the same frequency, but for a longer duration with Tesio catheters (76% +/- 32%
      over 100 monthly measurements versus DL catheter, 57% +/- 45% over 54 monthly
      measurements). Our clinical practice was to replace cuffed catheters when
      adequate dialysis could not be delivered. We conclude that Tesio catheters
      provide superior performance compared with DL catheters in terms of catheter
      survival, infection rates, and duration of adequate performance.

PMID- 11532687
TI  - Family history of end-stage renal disease does not predict dialytic survival.
AB  - Familial aggregation of end-stage renal disease (ESRD) is frequently observed in
      the common causes of kidney failure. It is unknown whether the clinical course of
      nephropathy differs based on an individual's family history of ESRD. The ESRD
      Network 6 Family History of ESRD database was analyzed to compare dialytic
      survival among patients with first- or second-degree relatives on dialysis
      therapy (positive family history) with those lacking relatives with ESRD
      (negative family history). Study participants included 3,442 adult, black or
      white, incident patients with ESRD who initiated dialysis therapy in ESRD Network
      6 facilities in 1995 and participated in the Network-sponsored Family History of
      ESRD study. All deaths were reported to the Network and used to calculate
      mortality rates. The relative risk for death was used to compare rates between
      levels of patient characteristics. Multivariate analyses used proportional
      hazards regression. Overall, 730 patients (21.2%) had a positive family history
      of ESRD. Black patients, those who were younger at the onset of ESRD, patients
      with greater degrees of functional status, and women were more likely to have a
      positive family history. During 9,000 patient-years of follow-up, 1,599 patients
      died (17.8 deaths/100 dialysis-years). Univariate analyses showed that patients
      with a positive family history of ESRD had 20% lower mortality than those with a
      negative family history of ESRD (relative risk, 0.80; 95% confidence interval,
      0.7 to 0.9; P = 0.001). Older age, white race, diabetic nephropathy, lower
      functional status, lower serum albumin level, congestive heart failure, and
      ischemic heart disease also were associated with greater mortality rates.
      Multivariate analyses showed that only older age at onset of ESRD, white race,
      low functional status, ESRD caused by diabetes, and congestive heart failure were
      associated with increased mortality. A family history of ESRD in either first- or
      second-degree relatives was no longer a significant determinant of survival. We
      conclude that familial clustering of ESRD does not significantly impact on
      dialytic survival after controlling for the competing effects of patient race,
      age of ESRD onset, and the presence of diabetes mellitus.

PMID- 11532689
TI  - Hemodialysis access placement with preoperative noninvasive vascular mapping:
      comparison between patients with and without diabetes.
AB  - We retrospectively analyzed data on preoperative vascular mapping in 195
      consecutive patients to investigate the common belief that patients with diabetes
      are poor candidates to have an arteriovenous fistula placed as dialysis access
      because they lack suitable blood vessels. There was no difference in venous
      diameter, arterial diameter, and arterial peak systolic velocity measurements
      between patients with and without diabetes. Patients with diabetes had a greater
      prevalence of vascular calcifications and greater cuff measurements of systolic
      segmental arterial pressure. In 140 of 195 patients, subsequent vascular access
      surgery had been performed in our institution, and 127 of these patients were on
      hemodialysis therapy at the end of the study period. There was no difference in
      the prevalence of fistula placement (66% versus 60%; chi-square = 2.6; df = 2; P
      = 0.28, not significant [NS]) and percentage of functioning fistulae between
      patients with and without diabetes (67% versus 62%; chi-square = 0.27; df = 1; P
      = 0.61, NS). The percentage of patients dialyzed through a temporary catheter was
      equal in patients with and without diabetes (18%). In summary, patients with
      diabetes seem to be as good candidates for arteriovenous fistula placement as
      patients without diabetes. Additional studies are required to determine the long
      term outcome of fistulae in patients with diabetes.

PMID- 11532690
TI  - Relationship between effective ionic dialysance and in vivo urea clearance during
      hemodialysis.
AB  - Effective ionic dialysance (EID) can be measured from dialyzer inlet and outlet
      conductivity changes following two steps of dialysate conductivity. Relationships
      between EID and in vivo urea clearances were studied four times per hemodialysis
      treatment in eight patients, each undergoing six hemodialysis treatments (192
      data sets). Dialyzer blood flow was varied from 190 to 500 mL/min. Dialysate flow
      was constant (751 to 771 mL/min), and a standard dialyzer (700 HG; Cobe,
      Lakewood, CO) was used. Double samples were drawn for arterial, venous, and
      dialysate urea measurements. Two laboratory values were missing. Twelve
      unreliable laboratory values indicated by divergent results were excluded. Urea
      clearances were calculated by formulae converting whole-blood to blood-water urea
      clearances. EID was measured using Diascan (Gambro-Dasco, Medolla, Italy). Mass
      balance was checked by comparison of dialysate and blood-water urea clearances.
      Divergent results between dialysate and blood-water urea clearance values led to
      the exclusion of an additional three laboratory values. A small error (4.2%) in
      urea mass balance was found (dialysate greater than blood-water urea clearances).
      A total of 175 data sets were compared. EID showed excellent correlation with
      blood-water urea clearances (r = 0.92) over the line of identity, with a mean
      difference of -3.5 mL/min (-1%), and similarly with dialysate urea clearances (r
      = 0.92; mean difference, -13.4 mL/min; -5%). For both blood- and dialysate-side
      comparisons, differences increased with greater clearances. Because EID is an
      effective clearance and urea clearance is a measure of dialyzer clearance, the
      curves were corrected for cardiopulmonary recirculation; access recirculation was
      zero (Transonic monitor; Transonic Systems Inc, Ithaca, NY). For cardiopulmonary
      recirculation correction, cardiac output and access flows were assumed to be 6.4
      L and 1.46 L/min. Corrected data show EID correlates with blood-side urea
      clearance (r = 0.92), with a mean difference of +7.3 mL/min (3.3%), and is
      constant over the range of clearances. EID correlated with dialysate urea
      clearance (r = 0.92) with virtually no difference. The difference on the blood
      side is consistent with the urea mass balance error found. These data indicate
      that EID using Diascan can provide an accurate indication of effective urea
      clearances obtained during hemodialysis and is of value in monitoring dialysis
      adequacy.

PMID- 11532691
TI  - Increases in mass transfer-area coefficients and urea Kt/V with increasing
      dialysate flow rate are greater for high-flux dialyzers.
AB  - The hemodialyzer mass transfer-area coefficient (K(o)A) for urea increases with
      increasing dialysate flow rate (Q(d)). The magnitude of the increase in K(o)A
      varies depending on the particular dialyzer under consideration; however,
      dialyzer properties that govern this phenomenon have not been established. We
      hypothesized that Q(d)-dependent increases in K(o)As are influenced by the water
      permeability of the dialysis membrane. We evaluated in vitro the effect of blood
      flow rate (Q(b)) and Q(d) on urea and creatinine K(o)As for two low-flux
      (Polyflux 6L and 8L) and two high-flux (Polyflux 14S and 17S) dialyzers
      containing Polyamide S membranes with similar membrane surface areas. Additional
      experiments were also performed on high-flux dialyzers containing Polyamide S
      membranes with very large surface areas (Polyflux 21S and 24S). K(o)As,
      calculated from the mean of blood- and dialysate-side clearances, were determined
      at zero net ultrafiltration for three different Q(b) and Q(d) combinations: Q(b)
      of 300 mL/min and Q(d) of 500 mL/min; Q(b) of 450 mL/min and Q(d) of 500 mL/min;
      and Q(b) of 450 mL/min and Q(d) of 800 mL/min. Urea and creatinine K(o)As were
      independent of the Q(b) but increased when Q(d) was increased from 500 to 800
      mL/min. These increases in both urea and creatinine K(o)As were greater for high
      flux than low-flux dialyzers (P < 0.0001). As expected, urea and creatinine
      K(o)As also increased with increasing membrane surface area. We conclude that
      dialysis membrane water permeability (or flux) is a dialyzer property that
      influences the dependence of small-solute K(o)As and clearance on Q(d). Whether
      this phenomenon is caused by enhanced internal filtration for dialyzers
      containing high-flux membranes requires further study.

PMID- 11532692
TI  - Life satisfaction in renal transplant recipients: preliminary results from the
      transplant learning center.
AB  - The Transplant Learning Center (TLC) was designed to improve quality of life
      (QOL) and preserve graft function in solid-organ transplant recipients. To meet
      the specific goals of the program, the Life Satisfaction Index and Transplant
      Care Index were designed to serve as composite measures for measuring transplant
      specific QOL and the ability to care for a transplant, respectively. In this
      study, we analyzed self-reported health information to examine relationships
      between comorbidities and individual posttransplantation side effects, life
      satisfaction, and transplant care, defined by renal transplant recipients.
      Patients entered the TLC through self-referral or referral by a health
      professional. Included in the analysis were 3,676 TLC enrollees with a mean time
      since transplantation of 4.8 years. Comorbidities and adverse effects were
      common, with high blood pressure reported by 89% of respondents and unusual hair
      growth reported by 70%. Sexual dysfunction and headache had a greater impact on
      QOL than more common adverse effects, such as changes in body and facial shape,
      hirsutism, and tremor. Regression modeling was used to identify the most
      significant associations between QOL indices and structural (nonmedical),
      medical, and psychosocial factors. Greater life satisfaction was most strongly
      associated with being in control of one's health and living a normally active
      life with satisfying emotional relationships. Management of such clinical
      problems as adverse effects of medication and nonadherence should be informed by
      the patient's perspective. Clinicians should actively solicit information about
      physical activity, appearance concerns, side effects of medications,
      nonadherence, and sexual and relationship issues when evaluating renal transplant
      recipients.

PMID- 11532693
TI  - Recurrent IgA nephropathy in renal transplant allografts.
AB  - Previous reports of renal transplantation for patients with underlying
      immunoglobulin A (IgA) nephropathy suggested a recurrence rate greater than 50%
      for transplant IgA nephropathy. Initially regarded as a benign condition, more
      recent data showed that recurrent transplant IgA nephropathy may be a significant
      contributor to graft loss. We performed a retrospective analysis in a single
      center of 48 kidney transplant recipients, all of Chinese origin, with biopsy
      proven IgA nephropathy as the cause of end-stage renal failure to determine the
      recurrence rate of IgA nephropathy in the transplant allograft and subsequent
      clinical course in Chinese patients. Median duration of follow-up was 52 months
      (range, 18 to 155 months). Fourteen patients (29%) had biopsy-confirmed recurrent
      transplant IgA nephropathy after a median of 52 months (interquartile range, 23
      to 82 months) posttransplantation. Recurrent transplant IgA nephropathy was
      associated with greater serum IgA levels (P = 0.01). The presence of HLA-A2 in
      transplant recipients (P = 0.002) appeared to protect them from developing
      recurrent IgA nephropathy in the transplant allograft. Twenty-nine percent of
      patients with recurrent transplant IgA nephropathy had progressive deterioration
      of graft function. The progressive graft dysfunction (GD) rate was greater in
      patients with a transplant from a living related donor (LRD; 21%) compared with
      those with a transplant from a cadaveric or living unrelated donor (URD; 3%; P =
      0.062). Although the cumulative graft survival rate was 100% at 5 years for
      transplants from both LRDs and URDs, the 10-year graft survival rate was only 63%
      for a graft from an LRD versus 93% for a URD (log-rank test, P = 0.19). A review
      of other reported series of recurrent transplant IgA nephropathy also showed an
      apparently greater incidence of GD for a graft from an LRD (28%) compared with a
      URD (15%). Our data suggest that although recurrent transplant IgA nephropathy is
      highly prevalent among the Chinese population, the risk for disease recurrence is
      not particularly increased compared with other ethnic groups. The trend toward a
      greater risk for GD for living related compared with unrelated allografts in
      patients with IgA nephropathy needs to be confirmed with further prospective
      study.

PMID- 11532694
TI  - Regulation of renal proximal tubular epithelial cell fibroblast growth factor-2
      generation by heparin.
AB  - Progression of renal disease is closely correlated to the degree of renal
      interstitial fibrosis, and evidence is increasing that epithelial cells of the
      renal proximal tubule (PTCs) may contribute to its pathogenesis. Such cytokines
      as basic fibroblast growth factor (FGF-2) have been implicated in progressive
      renal injury, and we previously showed that PTCs are a source of this cytokine.
      FGF-2 is characterized by its high affinity for heparin, and numerous studies
      have suggested that heparin may modify the progression of renal disease. The
      current study examined how heparin influenced FGF-2 generation and bioactivity in
      the human renal epithelial PTC line, HK-2. Incubation of HK-2 cells with heparin
      led to a dose- and time-dependent increase in FGF-2 concentration in the culture
      supernatant that was not accompanied by alterations in FGF-2 messenger RNA
      expression, assessed by reverse-transcriptase polymerase chain reaction and
      Northern analysis. The heparin-induced increase in FGF-2 concentration was
      accompanied by a decrease in the amount of FGF-2 bound to the extracellular
      matrix, although this accounted for only a small proportion of the total FGF-2
      generated. Induction of FGF-2 by 2-O-desulfated heparin, together with a
      reduction in total cell-associated FGF-2 and anti-FGF-2 antibody binding to fixed
      permeabilized cells after the addition of heparin, suggested that the FGF-2
      released was mainly derived from a preformed intracellular source. That FGF-2 was
      predominantly derived from an intracellular pool was also confirmed by pulse
      chase experiments. The addition of heparin resulted in the generation of
      bioinactive FGF-2, judged by in vitro fibroblast proliferation. Conversely,
      heparitinase treatment of supernatant samples from heparin-treated cells and the
      addition of 2-O-desulfated heparin resulted in the generation of active FGF-2,
      suggesting that the generation of bioinactive FGF-2 was related to binding of FGF
      2 by extracellular heparin after its release from cells. These data show that
      heparin depletes both the cell and surrounding matrix of FGF-2 and suggest that
      FGF-2 released from cells was mainly derived from a preformed intracellular
      source. Furthermore, FGF-2 released from epithelial PTCs after the application of
      heparin was bioinactive. This likely resulted from released FGF-2 binding to an
      excess of extracellular heparin. Results presented here therefore suggest a
      mechanism by which heparin, through its effect on depletion of matrix and cells
      of FGF-2 and its generation in an inactive form, may influence progressive renal
      interstitial fibrosis.

PMID- 11532695
TI  - Systemic adenosine given after ischemia protects renal function via A(2a)
      adenosine receptor activation.
AB  - Ischemia and reperfusion during renal transplant and aortic surgery result in
      renal ischemic-reperfusion injury. Previously, we showed that preischemic
      adenosine treatment protects renal function via A(1) adenosine receptor (AR)
      activation. In contrast, in the cardiac and pulmonary systems, postischemic
      adenosine has potent anti-inflammatory attributes and is protective against
      reperfusion injury via activation of A(2a) ARs. We questioned whether adenosine
      given after an ischemic insult protects renal function in rats, and we sought to
      determine the AR subtype and intracellular second messengers involved. Rats were
      randomized to a sham operation, 45 minutes of renal ischemia and reperfusion and
      treatments with systemic adenosine or selective AR agonists and antagonists, or
      treatments of dibutyryl cyclic adenosine monophosphate (cAMP) after 45 minutes of
      renal ischemia but before reperfusion. Forty-five minutes of renal ischemia
      followed by 24 hours of reperfusion led to severe renal dysfunction as indicated
      by marked rises in creatinine and histologically evident renal tubular damage.
      Adenosine treatment after ischemia protected renal function and improved tubular
      histology. This protection was mediated via A(2a) AR activation because the A(2a)
      selective AR agonist [4-((N-ethyl-5'-carbamoyadenos-2-yl)-aminoethyl)
      phenylpropionic acid (CGS-21680)] mimics adenosine-induced renal protection, and
      the A(2a)-selective AR antagonist [8-(3-chlorostyryl)caffeine (CSC)] blocks
      adenosine-induced renal protection. A(1) or A(3) AR agonists and antagonists did
      not mimic and block adenosine-induced renal protection. The signaling
      intermediates of A(2a) AR-mediated renal protection appear to include cAMP
      because dibutyryl cAMP mimicked adenosine and CGS-21680 mediated renal
      protection. Rat kidneys can be protected against reperfusion injury via
      postischemic A(2a) AR activation or cAMP. These data suggest that A(2a) adenosine
      agonists may have clinically beneficial implications when renal ischemia is
      unavoidable.

PMID- 11532696
TI  - Renal handling of human apolipoprotein(a) and its fragments in the rat.
AB  - The sites and mechanisms of the catabolism of atherogenic lipoprotein(a) (Lp(a))
      are not well understood. Lp(a) is increased in patients with end-stage renal
      disease, suggesting a renal catabolism of Lp(a). To gain a better insight into
      renal handling of Lp(a), we established a heterologous rat model to study the
      renal catabolism of human Lp(a). Pure human Lp(a) was injected into Wistar rats,
      and animals were sacrificed at different time points (30 minutes to 24 hours).
      Intact Lp(a) was cleared from the circulation of injected rats with a half-life
      time of 14.5 hours. Strong intracellular immunostaining for apolipoprotein(a)
      (apo(a)) was observed in the cytoplasm of proximal tubular cells after 4, 8, and
      24 hours. Apolipoprotein B (apoB) was colocalized with glomerular apo(a) 1 to 8
      hours after Lp(a) injection, but renal capillaries and tubules remained negative.
      No relevant amounts of apo(a) fragments were found in the plasma of rats after
      injection of Lp(a). During all urine collection periods, apo(a) fragments with
      molecular weights of 50 to 160 kd were detected in the urine, however. Our
      results show that human Lp(a) injected into rats accumulates intracellularly in
      the rat kidney, and apo(a) fragments are excreted in the urine. The kidney
      apparently plays a major role in fragmentation of Lp(a). Despite the fact that
      rodents lack endogenous Lp(a), rats injected with human Lp(a) may provide a
      useful heterologous animal model to study the renal metabolism of Lp(a) further.

PMID- 11532697
TI  - Atrial thrombus and central venous dialysis catheters.
AB  - A native arteriovenous fistula is the first choice for hemodialysis access.
      Despite improved catheter designs and the use of internal jugular veins,
      thrombotic complications still occur when tunneled central venous catheters are
      used as an alternative. Although right atrial thrombus (RAT) is a well
      characterized complication of long-term central venous cannulation, particularly
      when used for parenteral nutrition and chemotherapy in pediatric practice, only 9
      reported cases previously have been associated with the long-term use of central
      venous catheters for hemodialysis. We report five cases of RAT seen at our unit
      between 1994 and 1998 in patients who had been dialyzed using tunneled catheters.
      In four of five cases, the diagnosis was made during the investigation of
      hemoptysis or dyspnea. In the fifth case, a screening transthoracic
      echocardiogram revealed the thrombus. Three of five of the patients suffered
      pulmonary emboli, and a fourth patient had an unexplained electromechanical
      dissociation cardiac arrest without definite evidence of pulmonary embolus. Our
      experience suggests that anticoagulated patients with RAT remain at risk of
      pulmonary embolism. One of our patients successfully underwent atrial
      thrombectomy. In four of five of our cases and four of nine cases in the
      literature, the central venous catheter tip was within the right atrium.
      Positioning of the central venous catheter tip low down in the superior vena cava
      or in the right atrium has been advocated to improve dialysis adequacy and to
      reduce the incidence of catheter thrombosis. However, placement of the catheter
      tip within the right atrium may be associated with an increased risk of RAT.

PMID- 11532698
TI  - Fibrosing cholestatic hepatitis-like syndrome in hepatitis B virus-negative and
      hepatitis C virus-negative renal transplant recipients.
AB  - Cholestatic hepatitis and diffuse liver fibrosis have been described in
      immunosuppressed patients with hepatitis B virus or hepatitis C virus infection
      as fibrosing cholestatic hepatitis (FCH). FCH is characterized by cholestasis,
      with only a modest increase in aminotransferase levels. The pathologic picture
      typically shows periportal and perisinusoidal fibrosis, scarce mixed infiltrates,
      hepatocellular ballooning, and histologic cholestasis. We report two patients
      with diffuse fibrosis and cholestasis quite similar to the histologic picture of
      FCH, but in whom neither hepatitis B virus nor hepatitis C virus infection could
      be shown, highlighting the potential contribution of cytomegalovirus infection
      and azathioprine toxicity in the development of this severe complication of solid
      organ transplantation.

PMID- 11532699
TI  - Cultured skin fibroblasts as an in vitro model to assess phenotypic features in
      subjects with diabetic nephropathy.

PMID- 11532700
TI  - Ace inhibitors and erythropoietin responsiveness.

PMID- 11532701
TI  - Is there hope for preventing or slowing the progression of chronic renal disease?
      More support for the role of growth factors.

PMID- 11532702
TI  - A novel etiology of renal allograft dysfunction.

PMID- 11532703
TI  - Fluid balance and kidney function in space: introduction.

PMID- 11532704
TI  - Validity of microgravity simulation models on earth.
AB  - Many studies have used water immersion and head-down bed rest as experimental
      models to simulate responses to microgravity. However, some data collected during
      space missions are at variance or in contrast with observations collected from
      experimental models. These discrepancies could reflect incomplete knowledge of
      the characteristics inherent to each model. During water immersion, the
      hydrostatic pressure lowers the peripheral vascular capacity and causes increased
      thoracic blood volume and high vascular perfusion. In turn, these changes lead to
      high urinary flow, low vasomotor tone, and a high rate of water exchange between
      interstitium and plasma. In contrast, the increase in thoracic blood volume
      during a space mission is combined with stimulated orthosympathetic tone and
      lowered urine flow. During bed rest, body tissues are compressed by pressure from
      gravity, whereas microgravity causes a negative pressure around the body. The
      differences in renal function between space and experimental models appear to be
      explained by the physical forces affecting tissues and hemodynamics as well as by
      the changes secondary to these forces. These differences may help in selecting
      experimental models to study possible effects of microgravity.

PMID- 11532705
TI  - Renal hemodynamics in space.
AB  - Renal excretory function and hemodynamics are determined by the effective
      circulating plasma volume as well as by the interplay of systemic and local
      vasoconstrictors and vasodilators. Microgravity results in a headward shift of
      body fluid. Because the control conditions of astronauts were poorly defined in
      many studies, controversial results have been obtained regarding diuresis and
      natriuresis as well as renal hemodynamic changes in response to increased central
      blood volume, especially during the initial phase of space flight. Renal
      excretory function and renal hemodynamics in microgravity are affected in a
      complex fashion, because during the initial phase of space flight, variable
      mechanisms become operative to modulate the effects of increased central blood
      volume. They include interactions between vasodilators (dopamine, atrial
      natriuretic peptide, and prostaglandins) and vasoconstrictors (sympathetic
      nervous system and the renin-angiotensin system). The available data suggest a
      moderate rise in glomerular filtration rate during the first 2 days after launch
      without a significant increase in effective renal plasma flow. In contrast, too
      few data regarding the effects of space flight on renal function during the first
      12 hours after launch are available and are, in addition, partly contradictory.
      Thus, detailed and well-controlled studies are required to shed more light on the
      role of the various factors besides microgravity that determine systemic and
      renal hemodynamics and renal excretory function during the different stages of
      space flight.

PMID- 11532706
TI  - Renal and sympathoadrenal responses in space.
AB  - According to a classic hypothesis, weightlessness should promote the renal
      excretion rate of sodium and water and lead to a fluid- and electrolyte-depleted
      state. This hypothesis is based on experiments in which weightlessness has been
      simulated in humans by head-down bed rest and water immersion. However, after 5
      to 6 days of space mission, the diuretic and natriuretic responses to an
      intravenous isotonic saline load were attenuated and plasma norepinephrine and
      renin concentrations increased compared with those of the acute supine position
      before flight. Renal fluid excretion after an oral water load was also attenuated
      in space. Similar decreases were not observed during head-down bed rest.
      Sympathetic activity is of major importance in regulating blood volume and renal
      function. Studies in space have indicated that, compared with that while in a
      supine position on Earth, sympathoadrenal activity is increased during space
      flights as measured using plasma concentration and urinary excretion of
      norepinephrine and epinephrine. The space-induced activation of antinatriuretic
      mechanisms and sympathoadrenal activity could have been caused by early in-flight
      reduction in total and central blood volume. The decreased plasma volume may be
      explained by such factors as redistribution of plasma from the lower to the upper
      body (thin legs and puffy face), reduced food intake, and decreased muscle
      activity. The decrease in plasma volume and the subsequent increase in
      sympathetic activity is due, at least in part, to the abrupt cessation of
      activity in large muscle groups during microgravity, which normally counteracts
      the effects of gravity in the upright posture. This would lead to accumulation of
      albumin and fluid in the interstitial space.

PMID- 11532707
TI  - Water and sodium balance in space.
AB  - We have previously shown that fluid balances and body fluid regulation in
      microgravity (microG) differ from those on Earth (Drummer et al, Eur J Physiol
      441:R66-R72, 2000). Arriving in microG leads to a redistribution of body fluid
      composed of a shift of fluid to the upper part of the body and an exaggerated
      extravasation very early in-flight. The mechanisms for the increased vascular
      permeability are not known. Evaporation, oral hydration, and urinary fluid
      excretion, the major components of water balance, are generally diminished during
      space flight compared with conditions on Earth. Nevertheless, cumulative water
      balance and total body water content are stable during flight if hydration,
      nutritional energy supply, and protection of muscle mass are at an acceptable
      level. Recent water balance data disclose that the phenomenon of an absolute
      water loss during space flight, which has often been reported in the past, is not
      a consequence of the variable microG. The handling of sodium, however, is
      considerably affected by microG. Sodium-retaining endocrine systems, such as
      renin-aldosterone and catecholamines, are much more activated during microG than
      on Earth. Despite a comparable oral sodium supply, urinary sodium excretion is
      diminished and a considerable amount of sodium is retained-without accumulating
      in the intravascular space. An enormous storage capacity for sodium in the
      extravascular space and a mechanism that allows the dissociation between water
      and sodium handling likely contribute to the fluid balance adaptation in
      weightlessness.

PMID- 11532708
TI  - Body mass changes, energy, and protein metabolism in space.
AB  - Most astronauts lose body mass during their stay in microgravity. The early
      hypothesis, which attributed this phenomenon to an increase in diuresis and
      natriuresis after entering microgravity, is now untenable. Although a fluid shift
      from the lower to the upper body occurs, it does not lead to a marked fluid loss
      in the first 2 days of space flight. The continuous day-by-day body mass
      measurement during the Euromir 94 mission showed that there was a gradual
      reduction over the entire mission instead of a rapid loss of 2 to 3 kg at the
      beginning of a mission. The daily energy intake during this mission and the
      negative energy balances found in the Skylab and LMS-Mission show that lowered
      body mass is very likely caused by an insufficient energy consumption and its
      accompanying effects. These include the metabolization of endogenous energy
      stores, ie, glycogen, protein, and fat. Mobilization of glycogen and protein
      buffers will also cause the water that is bound to both to be lost. Thus, a
      gradual decrease in body mass and a concomitant reduction in total body fluid
      occurs without a significant increase in urine flow or natriuresis. In
      conclusion, the body mass loss in microgravity is likely a result of
      undernutrition instead of diuresis and natriuresis caused by the fluid shift.

PMID- 11532709
TI  - Revised hypothesis and future perspectives.
AB  - Results from space have been unexpected and not predictable from the results of
      ground-based simulations. Therefore, the concept of how weightlessness and
      gravity modulates the regulation of body fluids must be revised and a new
      simulation model developed. The main questions to ask in the future are the
      following: Does weightlessness induce a diuresis and natriuresis during the
      initial hours of space flight leading to an extracellular and intravascular fluid
      volume deficit? Can sodium in excess be stored in a hitherto unknown way,
      particularly during space flight? Why are fluid and sodium retaining systems
      activated by spaceflight? Why are the renal responses to saline and water stimuli
      in space attenuated compared with those of ground simulations? How can the
      effects of weightlessness on fluid and electrolyte regulation be correctly
      simulated on the ground? The information obtained from space may be of relevance
      to fluid and electrolyte balance in edematous patients.

PMID- 11532713
TI  - Hemoperitoneum in a continuous ambulatory peritoneal dialysis patient caused by a
      hepatocarcinoma treated with percutaneous embolization.
AB  - Hemoperitoneum is an infrequent but normally benign complication in continuous
      ambulatory peritoneal dialysis (CAPD) patients. It can occur at any time during
      peritoneal dialytic treatment. Hemoperitoneum is not associated with a specific
      disease and usually disappears spontaneously. In 20% of cases, however,
      hemoperitoneum is severe and requires specific investigation and emergency
      therapy. We report a case of hemoperitoneum in a 70-year-old, anti-hepatitic C
      virus-positive woman. After 48 months of CAPD treatment, a bloody peritoneal
      effluent developed, with severe anemia (hematocrit decreased from 30% to 20%). An
      abdominal computed tomography scan showed three hepatic lesions with signs of
      hepatic neoplasms; selective hepatic arteriography confirmed the diagnosis.
      Chemoembolization of the three lesions was performed, and hemoperitoneum
      disappeared within a few hours.

PMID- 11532714
TI  - Chyloperitoneum in a peritoneal dialysis patient.
AB  - A woman with end-stage renal disease underwent peritoneal dialysis. On initiation
      of treatment, there was turbid peritoneal dialysis fluid, which proved to be of
      chylous rather than inflammatory origin. A low-fat and medium-chain triglycerides
      diet induced visible clearing of the fluid and a decrease in its triglyceride
      concentration. Challenge with a high-fat diet produced two early recurrences.
      After 8 months, dietary fat no longer induced chyloperitoneum. The patient was
      able to continue peritoneal dialysis at home without a recurrence.

PMID- 11532716
TI  - Sodium and water disturbances in patients with Sheehan's syndrome.
AB  - Sheehan's syndrome has been attributed to ischemic damage of the pituitary gland
      or hypothalamic-pituitary stalk during the peripartum period. Well-described
      clinical features of Sheehan's syndrome include hypothyroidism, adrenal
      insufficiency, hypogonadism, growth hormone deficiency, hypoprolactinemia, and
      different sodium and water disturbances. The occurrence of sodium and water
      disturbances associated with Sheehan's syndrome depends on the degree of
      pituitary damage, time of onset since the initial pituitary insult, and
      concurrent medical conditions that also may play a role in sodium and water
      balance. We present a patient with Sheehan's syndrome with severe chronic
      hyponatremia; discuss a potential problem in the patient's management; and review
      the literature for various sodium and water disturbances, including acute and
      chronic hyponatremia as well as overt and subclinical central diabetes insipidus.
      Although Sheehan's syndrome is more prevalent in developing countries, the
      increasingly large immigrant population within the United States warrants better
      awareness of this syndrome and its potential complicating sodium and water
      disturbances. Prompt diagnosis and an understanding of the pathogenic mechanisms
      of sodium and water disturbances associated with Sheehan's syndrome may avoid
      potential treatment-related complications.

PMID- 11532715
TI  - Polyomavirus BK nephropathy in a kidney transplant recipient: critical issues of
      diagnosis and management.
AB  - Diagnosis of polyomavirus BK nephropathy and treatment by low-dose
      immunosuppression may be optimized by using surrogate markers, such as the
      detection of viral inclusion bearing cells in the urine and polyomavirus BK DNA
      in plasma by polymerase chain reaction. These markers were used prospectively in
      the management of a 44-year-old woman and led to the diagnosis of polyomavirus BK
      nephropathy at an early stage. The management was complicated by the concurrence
      of acute allograft rejection. Two treatment steps were initiated: antirejection
      therapy consisting of methylprednisolone for 3 days followed by lowering of the
      maintenance immunosuppression. This treatment resulted in a return of the serum
      creatinine concentration to the baseline of 1.6 mg/L, clearance of polyomavirus
      BK from plasma, and disappearance of viral inclusion bearing cells from the
      urine. After 2 months of stable allograft function, a control biopsy confirmed
      the resolution of polyomavirus BK nephropathy. Histologic signs of acute
      interstitial rejection were found and preemptively treated by methylprednisolone
      without altering the baseline regimen. Allograft function remained stable without
      evidence of recurrent polyomavirus BK nephropathy. This case shows the value of
      surrogate markers used in a prospective fashion for diagnosis and management of
      polyomavirus BK nephropathy with concurrent rejection.

PMID- 11532717
TI  - Changing concepts in the neurochemistry of schizophrenia.

PMID- 11532718
TI  - The emerging role of glutamate in the pathophysiology and treatment of
      schizophrenia.
AB  - OBJECTIVE: Research has implicated dysfunction of glutamatergic neurotransmission
      in the pathophysiology of schizophrenia. This review evaluates evidence from
      preclinical and clinical studies that brain glutamatergic neurotransmission is
      altered in schizophrenia, may affect symptom expression, and is modulated by
      antipsychotic drugs. METHOD: A comprehensive review of scientific articles
      published over the last decade that address the role of glutamate in the
      pathophysiology of schizophrenia was carried out. RESULTS: Glutamatergic neurons
      are the major excitatory pathways linking the cortex, limbic system, and
      thalamus, regions that have been implicated in schizophrenia. Postmortem studies
      have revealed alterations in pre- and postsynaptic markers for glutamatergic
      neurons in several brain regions in schizophrenia. The N-methyl-D-aspartic acid
      (NMDA) subtype of glutamate receptor may be particularly important as blockade of
      this receptor by the dissociative anesthetics reproduces in normal subjects the
      symptomatic manifestations of schizophrenia, including negative symptoms and
      cognitive impairments, and increases dopamine release in the mesolimbic system.
      Agents that indirectly enhance NMDA receptor function via the glycine modulatory
      site reduce negative symptoms and variably improve cognitive functioning in
      schizophrenic subjects receiving typical antipsychotics. CONCLUSIONS: Dysfunction
      of glutamatergic neurotransmission may play an important role in the
      pathophysiology of schizophrenia, especially of the negative symptoms and
      cognitive impairments associated with the disorder, and is a promising target for
      drug development.

PMID- 11532719
TI  - Working in a flawed mental health care system: an ethical challenge.
AB  - OBJECTIVE: Psychiatrists are under immense ethical pressure when practicing in
      circumstances that reasonable, informed colleagues would regard as not "good
      enough" in that they do not adequately meet the needs of patients and patients'
      families. This article is an examination of the ethical quandaries that ensue and
      options for response. METHOD: The authors explore the ways in which mental health
      systems may become flawed and compare philosophical arguments that deal with the
      predicament of working in such systems. RESULTS: The principle of fidelity to the
      patient is compromised in flawed systems, thus threatening professional
      integrity. Arguments for efficiency or the greater good in the provision of
      mental health care fail as remedies since they both lead to harms for particular
      clinical groups, as well as downgrading of a psychiatrist's integrity.
      CONCLUSIONS: Psychiatrists should submit to the principle of fidelity in working
      with patients. Since flawed systems undermine fidelity, threatening the patient's
      interests, psychiatrists are morally responsible for working to improve such
      systems.

PMID- 11532720
TI  - The human genome: gene expression profiling and schizophrenia.

PMID- 11532721
TI  - Treatment of conversion disorder in an African American Christian woman: cultural
      and social considerations.

PMID- 11532723
TI  - Expression of excitatory amino acid transporter transcripts in the thalamus of
      subjects with schizophrenia.
AB  - OBJECTIVE: Recent investigations of schizophrenia have targeted glutamatergic
      neurotransmission, since phencyclidine, an N-methyl-D-aspartate (NMDA) receptor
      antagonist, can induce schizophreniform psychosis. The authors previously
      reported alterations in thalamic NMDA receptor subunit expression in
      schizophrenia, consistent with the hypothesis that thalamic glutamatergic
      hypofunction may contribute to the pathophysiology of this illness. In this study
      they generalized this hypothesis to include other molecules of the glutamate
      synapse, specifically excitatory amino acid transporters (EAATs), whose normal
      expression and regulation in the thalamus may also be disrupted in subjects with
      schizophrenia. METHOD: In situ hybridization with riboprobes specific for the
      human excitatory amino acid transporter transcripts EAAT1, EAAT2, and EAAT3 was
      performed in discrete thalamic nuclei in persons with schizophrenia and
      comparison subjects. RESULTS: Higher expressions of transcripts encoding EAAT1
      and EAAT2, but not EAAT3, were detected in the thalamus of subjects with
      schizophrenia. CONCLUSIONS: These findings support the hypothesis of
      glutamatergic dysfunction in schizophrenia and suggest that molecules other than
      glutamate receptors are abnormally expressed in glutamatergic synapses in this
      illness.

PMID- 11532724
TI  - N-methyl-D-aspartic acid receptor expression in the dorsolateral prefrontal
      cortex of elderly patients with schizophrenia.
AB  - OBJECTIVE: The N-methyl-D-aspartic acid (NMDA) class of glutamate receptors has
      received attention in the pathophysiology of schizophrenia because of the
      similarity between some schizophrenic symptoms and symptoms caused by NMDA
      antagonists. To determine if NMDA receptor abnormalities were present at the mRNA
      level, expression of NMDA receptor (NR) subunits NR(1), NR(2A), and NR(2B) was
      measured in specimens from the dorsolateral prefrontal cortex and the occipital
      cortex of elderly patients with schizophrenia and normal elderly subjects.
      METHOD: Postmortem specimens from antemortem assessed and diagnosed elderly
      patients with schizophrenia (N=26) were compared with those from a
      neuropathologically and neuropsychiatrically normal elderly comparison group
      (N=13) and from patients with Alzheimer's disease (N=10). The mRNA expression of
      the NR(1), NR(2A), and NR(2B) subunits and of postsynaptic density 95 (PSD-95), a
      protein associated with postsynaptic NMDA receptors, was studied with
      quantitative real-time reverse transcriptase polymerase chain reaction. RESULTS:
      Expression of NR(1) and NR(2A) but not NR(2B) subunits was higher in the
      dorsolateral prefrontal cortex and the occipital cortex of patients with
      schizophrenia than in the normal and Alzheimer's disease groups. In contrast,
      NR(1) expression was significantly lower in the Alzheimer's disease group.
      Occipital cortex expression of PSD-95 was higher in the schizophrenic subjects
      and correlated strongly with the expression of NR(2A) and NR(2B) in both cortical
      regions and with expression of NR(1) in the occipital cortex. These results were
      not influenced by neuroleptic exposure history, postmortem interval, or age of
      the subject. CONCLUSIONS: NMDA receptor subunits are abnormally expressed in
      elderly patients with schizophrenia. The disproportionate expression of the NR(1)
      and NR(2A) subunits relative to NR(2B) expression may have implications for the
      pathophysiology of schizophrenia and the sensitivity of schizophrenic patients to
      glutamate and glutamatergic drugs.

PMID- 11532725
TI  - Lamina-specific deficits in parvalbumin-immunoreactive varicosities in the
      prefrontal cortex of subjects with schizophrenia: evidence for fewer projections
      from the thalamus.
AB  - OBJECTIVE: Neuronal number in the mediodorsal thalamic nucleus, the principal
      source of thalamic projections to the prefrontal cortex, has been reported to be
      lower in subjects with schizophrenia. The authors tested the hypothesis that
      schizophrenia is associated with a selective deficit in a marker of thalamic axon
      terminals in the middle layers of the prefrontal cortex, the primary zone of
      termination of thalamic axons. METHOD: The densities of parvalbumin
      immunoreactive varicosities (putative axon terminals) were determined in the
      superficial and middle layers of prefrontal cortex area 9 from 20 matched pairs
      of subjects with schizophrenia and normal comparison subjects. In order to
      determine the specificity of these observations, similar studies were conducted
      in subjects with major depressive disorder and in monkeys after 9-12 months of
      haloperidol treatment. RESULTS: The relative densities of parvalbumin
      immunoreactive varicosities did not differ between schizophrenic and comparison
      subjects in the superficial layers. However, in the middle layers, mean
      varicosity density was significantly lower (24% difference) in the subjects with
      schizophrenia. In contrast, neither subjects with major depressive disorder nor
      haloperidol-treated monkeys exhibited a middle-layer density of parvalbumin
      immunoreactive varicosities that was lower than that of their matched comparison
      groups. CONCLUSIONS: Although not definitive, these findings are consistent with
      the hypothesis of fewer projections from the mediodorsal thalamic nucleus to the
      prefrontal cortex in schizophrenic subjects and thus converge with other lines of
      evidence demonstrating an abnormality in thalamo-prefrontal cortical circuitry in
      persons with schizophrenia.

PMID- 11532726
TI  - Anterior cingulate cortex activity and impaired self-monitoring of performance in
      patients with schizophrenia: an event-related fMRI study.
AB  - OBJECTIVE: The authors examined brain activity associated with the internal
      monitoring of performance to test the hypothesis that error-related activity in
      the anterior cingulate cortex is impaired in patients with schizophrenia. METHOD:
      Seventeen patients with schizophrenia and 16 healthy comparison subjects
      underwent event-related functional magnetic resonance imaging during a continuous
      performance task; stimulus degradation was used to increase error rates. RESULTS:
      Comparison subjects, but not schizophrenic patients, showed error-related
      activity in the anterior cingulate cortex, and this difference in brain activity
      was significantly different across the two groups. Patients also showed less
      slowing of reaction time after error commission. CONCLUSIONS: Lower error-related
      activity in the anterior cingulate cortex and less performance adjustment after
      error commission are consistent with the hypothesis that disturbances in anterior
      cingulate cortex function are related to a specific alteration in an evaluative
      component of executive functioning-the internal monitoring of performance.

PMID- 11532727
TI  - Disturbed facial affect recognition in patients with schizophrenia associated
      with hypoactivity in distributed brain regions: a magnetoencephalographic study.
AB  - OBJECTIVE: The authors sought to identify brain mechanisms underlying the well
      documented facial affect recognition deficit in patients with schizophrenia.
      Since this deficit is stable over the course of the illness and relatively
      specific for schizophrenic disorders, it was expected that knowledge about the
      related brain mechanisms would provide substantial information about the
      pathophysiology of the illness. METHOD: Fifteen partly remitted schizophrenic
      inpatients and 12 healthy volunteers categorized facial expressions of emotion
      and performed two control tasks while magnetoencephalographic recordings were
      done by means of a 148-channel whole head system, which revealed foci of high
      cerebral activity and their evolution in time. Anatomical sites were defined
      through coregistrated magnetic resonance images. RESULTS: The
      magnetoencephalography data recorded in response to facial expressions of emotion
      revealed that patients generated weaker activations (primary current density) in
      inferior prefrontal, temporal, occipital, and inferior parietal areas at
      circumscribed latencies. Group differences did not occur in basic visual areas
      during a first sensory-related activation between 60 and 120 msec. Behavioral
      performance was associated with strength of activation in inferior prefrontal
      areas, the right posterior fusiform gyrus region, right anterior temporal cortex,
      and the right inferior parietal cortex. CONCLUSIONS: Disturbed facial affect
      recognition in schizophrenic patients might be a result of hypoactivity in
      distributed brain regions, some of them previously related to the pathophysiology
      of schizophrenic disorders. These regions are probably working within a spatially
      and temporally defined circuitry.

PMID- 11532728
TI  - Perceptual asymmetries in schizophrenia: subtype differences in left hemisphere
      dominance for dichotic fused words.
AB  - OBJECTIVE: Dichotic listening techniques have been used to study hemispheric
      dominance for language in schizophrenia. The authors' goal was to compare
      subjects with paranoid and undifferentiated subtypes of schizophrenia. METHOD:
      The Fused Rhymed Words Test was used to compare perceptual asymmetries in 16
      patients with paranoid schizophrenia, 28 patients with undifferentiated
      schizophrenia, and 29 healthy comparison subjects. RESULTS: Patients with
      paranoid schizophrenia had the largest left hemisphere advantage and patients
      with undifferentiated schizophrenia had the smallest. The asymmetry of healthy
      subjects was intermediate. Hemisphere advantage varied as a function of gender
      only in the patients with undifferentiated schizophrenia. CONCLUSIONS: The
      findings support the hypotheses that undifferentiated schizophrenia is associated
      with underactivation of left hemisphere resources for verbal processing and that
      paranoid schizophrenia is characterized by preserved left hemisphere processing.

PMID- 11532729
TI  - Six-year follow-up study of cognitive and functional status across the lifespan
      in schizophrenia: a comparison with Alzheimer's disease and normal aging.
AB  - OBJECTIVE: Follow-up studies of cognitive functions of poor-outcome (long-term
      institutionalized) elderly patients with schizophrenia have demonstrated
      deterioration over time, while stable cognitive functions over time have been
      reported for younger, better-outcome schizophrenic patients. This study examined
      whether cognitive changes in elderly schizophrenic patients with a history of
      long-term institutional stay extended to institutionalized younger patients. The
      rate of decline was compared to changes associated with Alzheimer's disease.
      METHOD: Patients with schizophrenia (N=107) age 20-80 years were followed over 6
      years and assessed with the Clinical Dementia Rating and the Mini-Mental State
      Examination. The schizophrenic subjects age 50 and older were compared to 136
      healthy comparison subjects and 118 Alzheimer's disease patients age 50 and older
      who were assessed over a similar follow-up period. RESULTS: There was a
      significant age group effect on the magnitude of cognitive decline for the
      schizophrenic subjects, with older subjects experiencing greater levels of
      decline over the follow-up. Neither the healthy individuals nor the Alzheimer's
      disease patients demonstrated similar age-related differences in the magnitude of
      cognitive change over the follow-up, with healthy comparison subjects showing no
      change and Alzheimer's disease patients manifesting decline regardless of age at
      the initiation of the follow-up. CONCLUSIONS: Institutionalized schizophrenic
      patients demonstrated an age-related pattern of cognitive change different from
      that observed for Alzheimer's disease patients and healthy individuals. The
      cognitive and functional status of these schizophrenic patients was fairly stable
      until late life, suggesting that cognitive change may not be occurring in younger
      patients over an interval as long as 6 years.

PMID- 11532730
TI  - Symptom reduction and suicide risk among patients treated with placebo in
      antipsychotic clinical trials: an analysis of the food and drug administration
      database.
AB  - OBJECTIVE: The assumption that psychotic patients assigned to placebo in clinical
      trials of antipsychotics are exposed to substantial morbidity and mortality is
      not based on data about what actually happens to such patients. This study
      assesses symptoms and risks of suicide and suicide attempts in psychotic patients
      assigned to receive placebo in clinical trials. METHOD: The authors used the Food
      and Drug Administration database to assess suicides, suicide attempts, and
      psychotic symptom reduction in clinical trials of three new antipsychotics.
      RESULTS: Among 10,118 participating patients, 26 committed suicide and 51
      attempted suicide. Rates of suicide and attempted suicide did not differ
      significantly between the placebo-treated and the drug-treated groups. Annual
      rates of suicide and attempted suicide based on patient exposure years were 1.8%
      and 3.3%, respectively, with placebo; 0.9% and 5.7% with an established
      antipsychotic; and 0.7% and 5.0% with a new antipsychotic. Symptom reduction was
      16.6% with new antipsychotics (N=1,203), 17.3% with established antipsychotics
      (N=261), and 1.1% with placebo (N=462). CONCLUSIONS: These data may help inform
      discussions about the use of placebo in antipsychotic clinical trials.

PMID- 11532731
TI  - A comparison of black and white women with binge eating disorder.
AB  - OBJECTIVE: Binge eating disorder was introduced in DSM-IV as a psychiatric
      disorder needing further study. This community-based study describes the
      relationship between race and clinical functioning in black and white women with
      and without binge eating disorder. METHOD: A group of 150 women with binge eating
      disorder (52 black, 98 white) and a race-matched group of 150 healthy comparison
      subjects were recruited from the community. Eating and psychiatric symptoms were
      assessed through interviews and self-report. RESULTS: Black and white women with
      binge eating disorder differed significantly on numerous eating disorder
      features, including binge frequency, restraint, history of other eating
      disorders, treatment-seeking behavior, and concerns with eating, weight, and
      shape. Black and white healthy comparison subjects differed significantly in
      obesity rates. CONCLUSIONS: For both black and white women, binge eating disorder
      was associated with significant impairment in clinical functioning. Yet, racial
      differences in clinical presentation underscore the importance of considering
      race in psychopathology research.

PMID- 11532732
TI  - Pregnancy complications and neonatal outcomes in women with eating disorders.
AB  - OBJECTIVE: This study reported pregnancy complications and neonatal outcomes for
      49 live births in a group of women with eating disorders who were prospectively
      followed. METHOD: Subjects were recruited from 246 women participating in a
      longitudinal study of anorexia nervosa and bulimia nervosa, now in its 12th year.
      Subjects were interviewed by trained assistants and completed a brief self-report
      instrument that assessed both birth statistics and birth-related complications.
      Medical records and/or self-report data describing the neonates' birth status
      were obtained. RESULTS: The majority of the women with eating disorders had
      normal pregnancies, resulting in healthy babies. Across the group, the mean
      length of pregnancy was 38.7 weeks, the mean birth weight was 7.6 lb, and mean
      Apgar scores at 1 and 5 minutes after birth were 8.2 and 9.0, respectively. Most
      outcomes were positive; however, three babies (6.1%) had birth defects, and 17
      (34.7%) of the women experienced postpartum depression. The mean number of
      obstetric complications in the group was 1.3, and 13 (26.5%) of the women
      delivered by cesarean section. Women who showed symptoms of either anorexia
      nervosa or bulimia nervosa during pregnancy had a higher frequency of birth by
      cesarean section and postpartum depression than did nonsymptomatic women.
      CONCLUSIONS: Pregnant women with active eating disorders appear to be at greater
      risk for delivery by cesarean section and for postpartum depression. Pregnant
      women with past or current eating disorders should be viewed as being at high
      risk and monitored closely both during and after pregnancy to optimize maternal
      and fetal outcomes.

PMID- 11532733
TI  - Comorbidity, impairment, and suicidality in subthreshold PTSD.
AB  - OBJECTIVE: Reliance on the categorical model of psychiatric disorders has led to
      neglected study of posttraumatic sequelae that fall short of full criteria for
      posttraumatic stress disorder (PTSD). Substantial disability and suicidal risk is
      associated with subthreshold PTSD, but this association has not been well
      studied. In addition, no studies have examined the role of comorbidity in
      explaining disability and impairment in subthreshold PTSD. METHOD: On National
      Anxiety Disorders Screening Day 1997, 2,608 out of 9,358 individuals screened for
      affective and anxiety disorders at 1,521 sites across the United States reported
      at least one PTSD symptom of at least 1 month's duration. Impairment, comorbid
      anxiety disorders, major depressive disorder, and rates of suicidality were
      determined and compared for individuals with no, one, two, three, or four (full
      PTSD) symptoms on a screening questionnaire. Regression analyses examined the
      relative contribution of subthreshold PTSD and comorbid disorders to impairment
      and suicidal ideation. RESULTS: Impairment, number of comorbid disorders, rates
      of comorbid major depressive disorder, and current suicidal ideation increased
      linearly and significantly with each increasing number of subthreshold PTSD
      symptoms. Individuals with subthreshold PTSD were at greater risk for suicidal
      ideation even after the authors controlled for the presence of comorbid major
      depressive disorder. CONCLUSIONS: Higher numbers of subthreshold PTSD symptoms
      were associated with greater impairment, comorbidity, and suicidal ideation.
      Disability and impairment found in previous studies of subthreshold PTSD symptoms
      may be related in part to the presence of comorbid disorders. However, the
      presence of subthreshold PTSD symptoms significantly raised the risk for suicidal
      ideation even after the authors controlled for major depressive disorder. Given
      the broad public health implications of these findings, more efforts are needed
      to identify subthreshold PTSD symptoms in clinical populations, epidemiologic
      surveys, and treatment studies.

PMID- 11532734
TI  - A longitudinal and retrospective study of PTSD among older prisoners of war.
AB  - OBJECTIVE: The authors examined the longitudinal changes in posttraumatic stress
      disorder (PTSD) symptom levels and prevalence rates over a 4-year time period
      among American former prisoners of war (POWs) from World War II and the Korean
      War. Retrospective symptom reports by World War II POWs dating back to shortly
      after repatriation were examined for 1) additional evidence of changing PTSD
      symptom levels and 2) evidence of PTSD cases with a long-delayed onset. METHOD:
      PTSD prevalence rates and symptom levels were measured by the Mississippi Scale
      for Combat-Related Posttraumatic Stress Disorder. For the longitudinal portion of
      the study, participants were 177 community-dwelling World War II and Korean POWs.
      For the retrospective portion, participants were 244 community-dwelling World War
      II POWs. RESULTS: PTSD prevalence rates and symptom levels increased
      significantly over the 4-year measurement interval. Retrospective symptom reports
      indicated that symptoms were highest shortly after the war, declined for several
      decades, and increased within the past two decades. Long-delayed onset of PTSD
      symptoms was rare. Demographic and psychosocial variables were used to
      characterize participants whose symptoms increased over 4 years and differentiate
      participants who reported a long-delayed symptom onset. CONCLUSIONS: Both
      longitudinal and retrospective data support a PTSD symptom pattern of immediate
      onset and gradual decline, followed by increasing PTSD symptom levels among older
      survivors of remote trauma.

PMID- 11532735
TI  - The Peritraumatic Distress Inventory: a proposed measure of PTSD criterion A2.
AB  - OBJECTIVE: Meeting criterion A2 for the diagnosis of posttraumatic stress
      disorder (PTSD) in DSM-IV requires that an individual have high levels of
      distress during or after the traumatic event. Because of the paucity of valid and
      reliable instruments for assessing such responses, the authors developed a 13
      item self-report measure, the Peritraumatic Distress Inventory, to obtain a
      quantitative measure of the level of distress experienced during and immediately
      after a traumatic event. METHOD: The cross-sectional study group comprised 702
      police officers and 301 matched nonpolice comparison subjects varying in
      ethnicity and gender who were exposed to a wide range of critical incidents.
      RESULTS: The Peritraumatic Distress Inventory was found to be internally
      consistent, with good test-retest reliability and good convergent and divergent
      validity. Even after controlling for peritraumatic dissociation and for general
      psychopathology, the authors found that Peritraumatic Distress Inventory scores
      correlated with two measures of posttraumatic stress symptoms. CONCLUSIONS: The
      Peritraumatic Distress Inventory holds promise as a measure of PTSD criterion A2.
      Future studies should prospectively examine the ability of the Peritraumatic
      Distress Inventory to predict PTSD and its associated biological and cognitive
      correlates in other trauma-exposed groups.

PMID- 11532736
TI  - Gender differences in posttraumatic stress disorder after motor vehicle
      accidents.
AB  - OBJECTIVE: Women have higher rates of posttraumatic stress disorder (PTSD) than
      men. The authors examined prior trauma, PTSD, major depression, anxiety disorder
      not including PTSD, and peritraumatic dissociation; current peritraumatic
      dissociation; and passenger injury as possible explanations for the different
      rates of acute PTSD in women and men after a serious motor vehicle accident.
      METHOD: Subjects age 18-65 years who had been in a serious motor vehicle accident
      (N=122) were assessed with the Structured Clinical Interview for DSM-III-R and
      the Peritraumatic Dissociative Experiences Questionnaire-Rater Version 1 month
      after the accident. RESULTS: Women did not differ from men in meeting the overall
      reexperiencing criterion for a diagnosis of PTSD (criterion B), but women were at
      greater risk for the specific reexperiencing symptoms of intense feelings of
      distress in situations similar to the motor vehicle accident and physical
      reactivity to memories of the motor vehicle accident. Women were 4.7 times more
      likely than men to meet the overall avoidance/numbing criterion (criterion C) and
      3.8 times more likely to meet the overall arousal criterion (criterion D). Women
      were more likely than men to report the criterion C symptoms of avoiding thoughts
      and situations associated with the accident, loss of interest in significant
      activities, and a sense of foreshortened future and the criterion D symptoms of
      trouble sleeping, difficulty concentrating, and exaggerated startle response.
      Multiple logistic regression analysis indicated that the gender differences in
      acute PTSD were not associated with prior trauma, PTSD, peritraumatic
      dissociation, major depression, or anxiety disorder not including PTSD or with
      passenger injury. However, peritraumatic dissociative symptoms at the time of the
      accident were associated with a significantly higher risk for acute PTSD in women
      than in men. CONCLUSIONS: Gender differences in peritraumatic dissociation may
      help explain differences in risk for PTSD and for some PTSD symptoms in women and
      men.

PMID- 11532737
TI  - Striatal dopamine transporters and cognitive functioning in healthy men and
      women.
AB  - OBJECTIVE: There is growing interest in distinguishing the biological bases of
      sex differences in behavior from environmental influences. Sex hormone levels
      seem to be related to some cognitive abilities, particularly memory, and the
      dopaminergic system participates in the mediation of memory. The dopamine
      transporter is the primary indicator of dopaminergic tone. This study
      investigated the relationship between cognition and dopamine transporter
      availability in healthy men and women. METHOD: Dopamine transporter levels were
      measured with a technetium-99m radiolabeled analog of cocaine, TRODAT-1, in 66
      healthy volunteers (30 men and 36 women). A neuropsychological battery designed
      to target functions associated with dopaminergic activity was administered during
      the uptake interval between the radiopharmaceutical injection and image
      acquisition. RESULTS: Women and younger participants had higher dopamine
      availability in the caudate nucleus, and these groups also performed better on
      verbal learning tasks. Furthermore, dopamine transporter availability was
      correlated with learning performance within groups. Relationships between
      dopamine availability in the caudate and putamen and executive and motor
      functioning were observed in women, but not in men. CONCLUSIONS: The results
      provide further evidence for age effects and sex differences in the
      neuromodulatory influences of dopamine on behavior in humans.

PMID- 11532738
TI  - Gender-related differences in the characteristics of problem gamblers using a
      gambling helpline.
AB  - OBJECTIVE: The characteristics of male and female gamblers utilizing a gambling
      helpline were examined to identify gender-related differences. METHOD: The
      authors performed logistic regression analyses on data obtained in 1998-1999 from
      callers to a gambling helpline serving southern New England. RESULTS: Of the 562
      phone calls used in the analyses, 349 (62.1%) were from male callers and 213
      (37.9%) from female callers. Gender-related differences were observed in reported
      patterns of gambling, gambling-related problems, borrowing and indebtedness,
      legal problems, suicidality, and treatment for mental health and gambling
      problems. Male gamblers were more likely than female gamblers to report problems
      with strategic or "face-to-face" forms of gambling, e.g., blackjack or poker.
      Female gamblers were more likely to report problems with nonstrategic, less
      interpersonally interactive forms of gambling, e.g., slot machines or bingo.
      Female gamblers were more likely to report receiving nongambling-related mental
      health treatment. Male gamblers were more likely to report a drug problem or an
      arrest related to gambling. High rates of debt and psychiatric symptoms related
      to gambling, including anxiety and depression, were observed in both groups.
      CONCLUSIONS: Individuals with gambling disorders have gender-related differences
      in underlying motivations to gamble and in problems generated by excessive
      gambling. Different strategies may be necessary to maximize treatment efficacy
      for men and for women with gambling problems.

PMID- 11532739
TI  - Traumatic grief treatment: a pilot study.
AB  - OBJECTIVE: The effects of a treatment program targeting debilitating grief
      symptoms were tested in a pilot study. METHOD: Twenty-one individuals
      experiencing traumatic grief were recruited for participation, and 13 completed
      the full 4-month protocol. The treatment protocol used imaginal re-living of the
      death, in vivo exposure to avoided activities and situations, and interpersonal
      therapy. RESULTS: Significant improvement in grief symptoms and associated
      anxiety and depression was observed for both completer and intent-to-treat
      groups. CONCLUSIONS: The traumatic grief treatment protocol appears to be a
      promising intervention for debilitating grief.

PMID- 11532740
TI  - Posttraumatic stress symptoms and salivary cortisol levels.
AB  - OBJECTIVE: This study assessed the relationship between posttraumatic stress
      symptoms and salivary cortisol levels after a severe ice storm. METHOD:
      Posttraumatic stress symptoms (Impact of Event Scale scores) and salivary
      cortisol levels were determined in 115 victims of an ice storm and in 27 healthy
      comparison subjects 1 month and approximately 1 year after the ice storm.
      RESULTS: One month after the storm, Impact of Event Scale scores for the victims
      (mean=20.31, SD=15.23) exceeded those of the comparison subjects (mean=5.30,
      SD=9.78) but were reduced approximately 1 year later (mean=14.01, SD=13.68). A
      quadratic relation was found to exist between Impact of Event Scale scores and
      cortisol levels. CONCLUSIONS: One month after the storm, cortisol levels were
      found to be elevated among the victims but were diminished among those with the
      highest Impact of Event Scale scores. This relationship was found not to exist
      approximately 1 year later.

PMID- 11532741
TI  - Vitamin B(6) in the treatment of tardive dyskinesia: a double-blind, placebo
      controlled, crossover study.
AB  - OBJECTIVE: The authors' goal was to conduct a double-blind trial of vitamin B(6)
      in the treatment of tardive dyskinesia in patients with schizophrenia. METHOD:
      Fifteen inpatients with schizophrenia who met research diagnostic criteria for
      tardive dyskinesia were randomly assigned to treatment with either vitamin B(6)
      or placebo for 4 weeks in a double-blind crossover paradigm. The Extrapyramidal
      Symptom Rating Scale was used to assess patients weekly. RESULTS: Mean scores on
      the parkinsonism and dyskinetic movement subscales of the Extrapyramidal Symptom
      Rating Scale were significantly better in the third week of treatment with
      vitamin B(6) than during the placebo period. CONCLUSIONS: Vitamin B(6) appears to
      be effective in reducing symptoms of tardive dyskinesia.

PMID- 11532742
TI  - Anxiolytic activity of atrial natriuretic peptide in patients with panic
      disorder.
AB  - OBJECTIVE: Preclinical evidence exists for the anxiolytic activity of atrial
      natriuretic peptide, which is released during lactate-induced panic attacks.
      Atrial natriuretic peptide receptor modulation may have antipanic activity in
      patients with panic disorder. METHOD: The effects of 150 microg of atrial
      natriuretic peptide and placebo on panic attacks induced by cholecystokinin
      tetrapeptide (CCK-4) (25 microg) were studied in 10 panic disorder patients. The
      panicogenic activity of CCK-4 was measured with the Acute Panic Inventory.
      RESULTS: Panic attacks occurred in seven patients in the placebo condition and in
      two patients in the atrial natriuretic peptide condition. CCK-4 administration
      was accompanied by a significant increase in Acute Panic Inventory scores.
      Pretreatment with atrial natriuretic peptide resulted in significantly lower
      Acute Panic Inventory scores than pretreatment with placebo. CONCLUSIONS: The
      results support the antipanic activity of atrial natriuretic peptide.
      Nonpeptidergic atrial natriuretic peptide receptor ligands may be ultimately used
      to treat anxiety disorders.

PMID- 11532743
TI  - Randomized study of the dopamine receptor agonist piribedil in the treatment of
      mild cognitive impairment.
AB  - OBJECTIVE: Age-related decrease in dopamine D(2) receptors is associated with
      cognitive decline in healthy elderly individuals. This study was an investigation
      of whether the dopamine receptor agonist piribedil improves global cognitive
      function in patients with mild cognitive impairment. METHOD: In a 90-day
      randomized double-blind study, treatment with piribedil was compared to placebo
      in 60 patients with clinically diagnosed mild cognitive impairment and a Mini
      Mental State Examination (MMSE) score of 21 to 25. The primary outcome was change
      in MMSE score. RESULTS: Of the 30 patients randomly assigned to each treatment
      group, 19 (63.3%) of those taking piribedil and eight (26.7%) of those treated
      with placebo had increases in MMSE scores, to 26 or more. The response rate and
      the mean increase in MMSE scores were significantly greater with piribedil.
      CONCLUSIONS: Patients with mild cognitive impairment had improvement in global
      cognitive function when treated with the dopamine receptor agonist piribedil. The
      results support the role of age-related dopamine decline in cognitive impairment
      of the elderly.

PMID- 11532744
TI  - Drug use and life style among college undergraduates: a 30-year longitudinal
      study.
AB  - OBJECTIVE: The authors examined trends in the prevalence of substance use and its
      relationship to attributes of life style among college students over a 30-year
      period. METHOD: They distributed anonymous questionnaires to 796 seniors at a
      large New England college in 1999, using methods essentially identical to those
      of their previous studies at the same college in 1969, 1978, and 1989. RESULTS:
      Most forms of drug use rose to a peak in 1978 then fell over the next 21 years,
      except for use of 3,4-methylenedioxymethamphetamine ("ecstasy"). On several
      variables, college substance users differed more sharply from nonusers in 1999
      than in previous decades. CONCLUSIONS: Although the study was limited to students
      at a single institution, its findings suggest that college drug use is generally
      declining and that users have increasingly diverged from nonusers in their values
      and life style.

PMID- 11532745
TI  - White matter lesions and season of birth of patients with bipolar affective
      disorder.
AB  - OBJECTIVE: It is established that patients with bipolar disorder have an excess
      of births in winter or early spring. The authors investigated a link between
      season of birth and white matter lesions with magnetic resonance imaging (MRI).
      METHOD: T(2)-weighted and proton density MRI scans were examined for 79 patients
      with bipolar disorder (DSM-IV) for the presence of deep subcortical and
      periventricular white matter lesions. The birth seasons of patients with white
      matter lesions were compared with those of the general population. RESULTS:
      Thirteen subjects exhibited deep subcortical white matter lesions, of whom nine
      (69.2%) were born in the winter months (January to March). Seven of these
      patients remained symptomatic, despite adequate treatment for more than 2 years.
      CONCLUSIONS: Birth season, illness outcome, and deep subcortical white matter
      lesions appear to be closely linked. Deep subcortical white matter lesions may be
      a marker of a toxic or infective insult in utero.

PMID- 11532746
TI  - Cycling into depression from a first episode of mania: a case-comparison study.
AB  - OBJECTIVE: The characteristics of patients who cycle from mania to major
      depression and the frequencies of these cycles remain poorly understood. METHOD:
      This study compared 28 patients with a first episode of mania who cycled into a
      major depressive episode without recovery from their index episode and 148
      patients with first-episode mania who did not cycle into depression. Patients
      were given extensive assessments at baseline and 6-, 12-, and 24-month follow
      ups. Comparisons between the two groups were made on demographic variables,
      clinical ratings, and outcome variables. RESULTS: Approximately 16% of the
      patients with a first episode of mania cycled into major depression. Patients who
      cycled into depression were more likely to have higher depressive scores at
      admission and tended to have the mixed subtype of bipolar disorder. CONCLUSIONS:
      Patients with first-episode mania who score high for depression at admission may
      be at greater risk of cycling into a major depressive episode.

PMID- 11532747
TI  - Early recognition of inherited disorders.

PMID- 11532748
TI  - Normal PET after long-term ECT.

PMID- 11532750
TI  - Treating depression in schizophrenia.

PMID- 11532752
TI  - Memory training in schizophrenia.

PMID- 11532753
TI  - Early age at first alcoholic drink.

PMID- 11532754
TI  - Adaptive functioning in schizophrenia.

PMID- 11532755
TI  - Climate and length of hospital stay.

PMID- 11532756
TI  - Gender differences in treatment response.

PMID- 11532759
TI  - Olfactory deficit in Alzheimer's disease?

PMID- 11532760
TI  - Olfactory deficit in Alzheimer's disease?

PMID- 11532762
TI  - Olfactory deficit in Alzheimer's disease?

PMID- 11532763
TI  - Anxiety in major depression.

PMID- 11532764
TI  - Antidepressant effects of hydrocortisone.

PMID- 11532779
TI  - Using validation sets for outcomes and exposure to infection in vaccine field
      studies.
AB  - Methods of adjusting for bias in estimates due to mismeasured or missing
      covariates and outcomes through the use of validation sets have been developed in
      many types of health studies. These methods can be employed for the efficient
      design and analysis of vaccine studies as well. On the one hand, nonspecific case
      definitions can lead to attenuated efficacy and effectiveness estimates, but
      confirmation by culture or a quick test of the infectious agent is also expensive
      and difficult. On the other hand, data on exposure to infection can influence
      estimates of vaccine efficacy, but good data on exposure are difficult to obtain.
      In this paper, the authors show how use of small validation sets can correct the
      bias of the estimates obtained from a large main study while maintaining
      efficiency. They illustrate the approach for outcomes using the example of
      influenza vaccine efficacy and effectiveness trials and illustrate the approach
      for exposure to infection using the example of a human immunodeficiency virus
      vaccine trial. The authors discuss challenges posed by infectious diseases in the
      use of currently available methods. Development of these efficient designs and
      methods of analysis for vaccine field studies will improve estimation of vaccine
      efficacy for both susceptibility and infectiousness, as well as estimation of
      indirect and overall effects of vaccination in community trials.

PMID- 11532781
TI  - Invited commentary: unexplained health problems after Gulf War Service--finding
      answers to complex questions.
AB  - Numerous studies have investigated the health problems reported by veterans of
      the Persian Gulf War, but important questions remain. Epidemiologic studies have
      consistently indicated that Gulf War veterans report unexplained symptoms at
      significantly higher rates than veteran comparison groups but that they have not
      experienced excess rates of disease-related mortality. Addressing unanswered
      questions surrounding post-Gulf-War health problems presents a complex challenge
      for researchers, but not an insurmountable one. Progress in understanding the
      role of potential etiologic factors can be made using epidemiologic approaches
      traditionally applied in the absence of individual exposure data, such as
      comparisons between veteran subgroups with differing illness profiles and
      deployment histories.

PMID- 11532780
TI  - Mortality among US veterans of the Persian Gulf War: 7-year follow-up.
AB  - To assess the long-term health consequences of the 1991 Persian Gulf War, the
      authors compared cause-specific mortality rates of 621,902 Gulf War veterans with
      those of 746,248 non-Gulf veterans, by gender, with adjustment for age, race,
      marital status, branch of service, and type of unit. Vital status follow-up began
      with the date of exit from the Persian Gulf theater (Gulf veterans) or May 1,
      1991 (control veterans). Follow-up for both groups ended on the date of death or
      December 31, 1997, whichever came first. Cox proportional hazards models were
      used for the multivariate analysis. For Gulf veterans, mortality risk was also
      assessed relative to the likelihood of exposure to nerve gas at Khamisiyah, Iraq.
      Among Gulf veterans, the significant excess of deaths due to motor vehicle
      accidents that was observed during the earlier postwar years had decreased
      steadily to levels found in non-Gulf veterans. The risk of death from natural
      causes remained lower among Gulf veterans compared with non-Gulf veterans. This
      was mainly accounted for by the relatively higher number of deaths related to
      human immunodeficiency virus infection among non-Gulf veterans. There was no
      statistically significant difference in cause-specific mortality among Gulf
      veterans relative to potential nerve gas exposure. The risk of death for both
      Gulf veterans and non-Gulf veterans stayed less than half of that expected in
      their civilian counterparts. The authors conclude that the excess risk of
      mortality from motor vehicle accidents that was associated with Gulf War service
      has dissipated after 7 years of follow-up.

PMID- 11532782
TI  - Homicide on the job: workplace and community determinants.
AB  - Homicide is the second leading cause of death on the job for workers in the
      United States. To identify workplace-level predictors of homicide risk, a case
      control study of worker killings in North Carolina in 1994-1998 was conducted.
      Workplaces were the units of analysis: case workplaces (n = 105) were those where
      a worker was killed during the study period, while controls (n = 210) were a
      density sample of North Carolina workplaces, matched on time and industry sector.
      Potential risk and protective factors were assessed in telephone interviews with
      workplace managers. Associations were measured by the exposure odds ratio and 95%
      confidence interval, estimated via conditional logistic regression.
      Characteristics associated with notably higher risk included being at the current
      location for 2 years or less (odds ratio (OR) = 5.3, 95% confidence interval
      (CI): 2.2, 12.6), having only one worker (OR = 2.9, 95% CI: 1.2, 7.2), and having
      night (OR = 4.9, 95% CI: 2.7, 8.8) or Saturday (OR = 4.2, 95% CI: 1.9, 9.2)
      hours. Workplaces with only male employees (OR = 3.1, 95% CI: 1.5, 6.5) or with
      African-American or Asian employees were also more likely to experience a
      killing. While few of the preceding risk factors are directly modifiable through
      workplace interventions, it is important to identify them before developing or
      evaluating preventive measures.

PMID- 11532783
TI  - Tracking of cardiovascular risk factors: the Tromso study, 1979-1995.
AB  - Tracking of cardiovascular risk factors (blood pressure, body mass index (BMI),
      and serum lipids) has not been studied much in a general, adult population. No
      known study has compared tracking of these factors for both sexes. In the present
      study, 17,710 men and women aged 20-61 years at baseline attended two or three
      population-based health surveys in Tromso, Norway, over 16 years (between 1979
      1980 and 1994-1995). Tracking coefficients were estimated by using different
      methods, and possible predictors of tracking were found. There was a high degree
      of tracking for BMI (overall tracking coefficients: 0.85 for men, 0.80 for
      women). Relatively high (or moderate) tracking was found for systolic blood
      pressure (respective sex-specific coefficients: 0.52, 0.54), diastolic blood
      pressure (0.48, 0.48), high density lipoprotein cholesterol (0.55, 0.64), and
      total cholesterol (0.77, 0.65). The lowest coefficients were for triglycerides
      (0.43, 0.39). Analysis of tracking in the upper sextile confirmed these results.
      Although some baseline predictors were associated with tracking, the effects were
      relatively weak. When predictors for tracking in the upper sextile were assessed,
      significant associations were found with relatively strong effects. No major sex
      differences were observed in tracking. However, women were more likely than men
      to remain in the upper sextile of systolic and diastolic blood pressures and of
      BMI.

PMID- 11532784
TI  - Relation of ascorbic acid to bone mineral density and self-reported fractures
      among US adults.
AB  - Ascorbic acid is an essential nutrient involved in collagen formation, and its
      deficiency is associated with abnormal bone development. To examine the relation
      of ascorbic acid to bone mineral density and the prevalence of self-reported
      fractures, the authors analyzed data collected from 13,080 adults enrolled in the
      Third National Health and Nutrition Examination Survey (NHANES III) during 1988
      1994. Because they identified three-way interactions among smoking, history of
      estrogen use, and dietary and serum ascorbic acid in postmenopausal women, they
      analyzed these relations stratified by smoking and estrogen use. Dietary ascorbic
      acid intake was independently associated with bone mineral density among
      premenopausal women (p = 0.002). Among men, serum ascorbic acid was associated in
      a nonlinear fashion with bone mineral density (p < 0.05), and dietary ascorbic
      acid intake was associated in a nonlinear fashion with self-reported fracture (p
      = 0.05). Among postmenopausal women without a history of smoking or estrogen use,
      serum ascorbic acid was unexpectedly associated with lower bone mineral density
      (p = 0.01). However, among postmenopausal women with a history of smoking and
      estrogen use, a standard deviation increase in serum ascorbic acid was associated
      with a 49% decrease in fracture prevalence (p = 0.001). Dietary and serum
      ascorbic acid measures were associated inconsistently with bone mineral density
      and self-reported fracture among adult participants in NHANES III.

PMID- 11532785
TI  - Phytoestrogen consumption and breast cancer risk in a multiethnic population: the
      Bay Area Breast Cancer Study.
AB  - Research on the relation between phytoestrogens and breast cancer risk has been
      limited in scope. Most epidemiologic studies have involved Asian women and have
      examined the effects of traditional soy foods (e.g., tofu), soy protein, or
      urinary excretion of phytoestrogens. The present study extends this research by
      examining the effects of a spectrum of phytoestrogenic compounds on breast cancer
      risk in non-Asian US women. African-American, Latina, and White women aged 35-79
      years, who were diagnosed with breast cancer between 1995 and 1998, were compared
      with women selected from the general population via random digit dialing.
      Interviews were conducted with 1,326 cases and 1,657 controls. Usual intake of
      specific phytoestrogenic compounds was assessed via a food frequency
      questionnaire and a newly developed nutrient database. Phytoestrogen intake was
      not associated with breast cancer risk (odds ratio = 1.0, 95% confidence
      interval: 0.80, 1.3 for the highest vs. lowest quartile). Results were similar
      for pre- and postmenopausal women, for women in each ethnic group, and for all
      seven phytoestrogenic compounds studied. Phytoestrogens appear to have little
      effect on breast cancer risk at the levels commonly consumed by non-Asian US
      women: an average intake equivalent to less than one serving of tofu per week.

PMID- 11532786
TI  - Physical activity and breast cancer risk in hispanic and non-hispanic white
      women.
AB  - To investigate breast cancer risk in Hispanic and non-Hispanic White women, the
      authors conducted a population-based case-control study of New Mexican women
      during 1992-1994 using incident breast cancer cases aged 35-74 years and
      frequency-matched controls selected using random digit dialing. Activity type and
      weekly duration of usual nonoccupational physical activity were used to calculate
      weekly metabolic equivalent (MET)-hours of total and vigorous physical activity
      (> or =5 METs). Conditional logistic regression models were fitted to estimate
      the relative risk of breast cancer for levels of physical activity and to assess
      the difference in effects by ethnicity, body mass index, energy intake, and
      menopausal status. Vigorous physical activity was associated with reduced breast
      cancer risk in both Hispanic and non-Hispanic White women. Women in the highest
      category of vigorous activity had lower risk of breast cancer (adjusted odds
      ratio = 0.34, 95% confidence interval: 0.22, 0.51 for Hispanic; adjusted odds
      ratio = 0.60, 95% confidence interval: 0.41, 0.89 for non-Hispanic White women)
      compared with women reporting no vigorous physical activity. Both pre- and
      postmenopausal Hispanic women showed decreasing risk with increasing level of
      activity. Physical activity was protective only among postmenopausal non-Hispanic
      White women. The effects of physical activity were independent from reproductive
      factors, usual body mass index, body mass index at age 18, adult weight gain, and
      total energy intake.

PMID- 11532787
TI  - Risk assessment for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) based on an
      epidemiologic study.
AB  - The International Agency for Research on Cancer (Lyon, France) recently concluded
      that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a human carcinogen. There have
      been few human studies and risk assessments with quantitative exposure data. The
      authors previously conducted exposure-response analyses based on estimated
      external TCDD exposure for 3,538 US male chemical workers and found a positive
      trend for all cancer with increasing cumulative exposure. In the present study,
      1988 data from 170 workers with both estimated external exposure and known serum
      TCDD levels were used to derive the relation between the two. This derived
      relation was used to estimate serum TCDD levels over time for all 3,538 workers,
      and new dose-response analyses were conducted by using cumulative serum level. A
      positive trend (p = 0.003) was found between estimated log cumulative TCDD serum
      level and cancer mortality. For males, the excess lifetime (75 years) risk of
      dying of cancer given a TCDD intake of 1.0 pg/kg of body weight per day, twice
      the background intake, was an estimated 0.05-0.9% above a background lifetime
      risk of cancer death of 12.4%. Data from this cohort are consistent with another
      epidemiologic risk assessment from Germany and support recent conclusions by the
      US Environmental Protection Agency.

PMID- 11532788
TI  - Effects of malaria during pregnancy on infant mortality in an area of low malaria
      transmission.
AB  - Malaria during pregnancy reduces birth weight, and low birth weight is a major
      determinant of infant mortality. The authors estimated the impact of malaria
      during pregnancy on infant mortality in a Karen population living in Thailand.
      Between 1993 and 1996, a cohort of 1,495 mothers and their infants was followed
      weekly from admission of the mother to antenatal clinics until the first birthday
      of the infant. Both falciparum malaria and vivax malaria during pregnancy were
      associated with low birth weight but did not shorten gestation. Febrile illness
      in the week before delivery was associated with premature birth. Preterm and full
      term low birth weight and fever in the week before delivery were associated with
      neonatal mortality. Maternal fevers close to term were also associated with the
      deaths of infants aged between 1 and 3 months, whereas no risk factors could be
      identified for deaths that occurred later in infancy. Thus, malaria during
      pregnancy increased neonatal mortality by lowering birth weight, whereas fever in
      the week before birth had a further independent effect in addition to inducing
      premature birth. The prevention of malaria in pregnancy and, thus, of malaria
      attributable low birth weight should increase the survival of young babies.

PMID- 11532789
TI  - Validity and reproducibility of a food frequency questionnaire for pregnant
      Finnish women.
AB  - The authors developed a self-administered 181-item food frequency questionnaire
      (FFQ) to assess dietary intake during pregnancy for Finnish women from August
      1995 to July 1996. In the validation study (n = 113), the data that were
      collected by using two 5-day food records completed during the eighth month of
      pregnancy were compared with FFQ data. The intake of foods and nutrients was
      higher as determined by FFQ than that assessed using food records. Pearson
      correlation coefficients for nutrients, after adjustment for energy, ranged from
      0.19 (vitamin E) to 0.70 (thiamin) and, for foods, from 0.03 (high-fat milk) to
      0.84 (low-fat milk). Energy adjustment improved the correlations for nutrients.
      Correction for attenuation improved correlations for both foods and nutrients. On
      average, 70% of the foods and 69% of the nutrients fell into the same or adjacent
      quintiles, according to the FFQ and the food record. In the reproducibility
      study, 111 women completed the FFQs twice at a 1-month interval. The intraclass
      correlation coefficients for nutrients ranged from 0.42 (ethanol) to 0.72
      (sucrose, riboflavin, and calcium), and for foods, they ranged from 0.44 (ice
      cream) to 0.91 (coffee). The authors conclude that the FFQ has an acceptable
      reproducibility and represents a useful tool for categorizing pregnant women
      according to their dietary intake.

PMID- 11532790
TI  - Relation of occupational exposure to respiratory symptoms and asthma in a general
      population sample: self-reported versus interview-based exposure data.
AB  - The objective of this study was to examine how the consistency of self-reported
      exposure to dust or gas, asbestos, and quartz varied between subjects with and
      those without respiratory symptoms and asthma in a Norwegian community sample ()
      in 1987-1988. Exposure characterization obtained in a structured work history
      interview was used as the "gold standard." The authors also wanted to assess how
      the exposure-disease relation differed when the exposure was based on self
      reported versus interview-obtained data. The prevalence of self-reported exposure
      to dust or gas, asbestos, and quartz was 28%, 5%, and 4%, respectively. The
      sensitivity of the self-reported exposure data varied from 21% to 64% and was
      higher in those with than in those without the respiratory disorders. The
      specificity varied from 78% to 100% and was lower in those with than in those
      without the respiratory disorders. The sex-, age-, and smoking-adjusted odds
      ratios of the respiratory disorders in those with exposure to dust or gas and to
      asbestos were only slightly reduced when misclassification was taken into
      account. The corresponding numbers for exposure to quartz were halved and lost
      their statistical significance when the misclassification was allowed for. In
      this general population sample, the self-reported occupational, airborne exposure
      data were differentially misclassified by disease status.

PMID- 11532791
TI  - Re: "assessing the impact of classical risk factors on myocardial infarction by
      rate advancement periods".

PMID- 11532793
TI  - The case for cothymia: mixed anxiety and depression as a single diagnosis.

PMID- 11532794
TI  - Genetic risk factors as possible causes of the variation in European suicide
      rates.

PMID- 11532795
TI  - Association between behaviour at age 3 years and adult criminality.
AB  - BACKGROUND: The continuity in antisocial behaviour into adulthood from middle
      childhood is well established but it is not clear whether this is also true of
      the pre-school period. AIMS: To determine whether pre-school behaviour problems
      increase the risk of later criminal convictions and add to risk associated with
      family and social circumstances. METHOD: The records of adult convictions were
      traced for a general population sample (n=828) initially assessed at age 3 years.
      RESULTS: The risk of having any adult conviction was related to soiling, daytime
      enuresis, activity level and management difficulties, and that of having an adult
      violent offence to recent-onset daytime enuresis, management difficulties and
      temper tantrums. The only other predictors of later convictions were the child's
      gender and social competence at age 3 years. CONCLUSIONS: The presence of
      specific behaviour problems in the pre-school period places the child at
      increased risk of being convicted of an adult offence. Family and social
      circumstances at age 3 years did not predict later convictions.

PMID- 11532796
TI  - Adolescents' self-reported problems as predictors of psychopathology in
      adulthood: 10-year follow-up study.
AB  - BACKGROUND: Knowledge of the course of psychopathology from adolescence into
      adulthood is needed to answer questions concerning origins and prognosis of
      psychopathology across a wide age range. AIMS: To investigate the 10-year course
      and predictive value of self-reported problems in adolescence in relation to
      psychopathology in adulthood. METHOD: Subjects from the general population, aged
      11-19 years, were assessed with the Youth Self-Report (YSR) at initial
      assessment, and with the Young Adult Self-Report (YASR), the Composite
      International Diagnostic Interview (CIDI) and three sections of the Diagnostic
      Interview Schedule (DIS) 10 years later. RESULTS: Of the subjects with deviant
      YSR total problem scores, 23% (males) and 22% (females) had deviant YASR total
      problem scores at follow-up. Subjects with initial deviant YSR total problem,
      internalising and externalising scores had higher prevalences of DSM-IV diagnoses
      at follow-up. CONCLUSIONS: Adolescent problems tended to persist into adulthood
      to a moderate degree. High rates of problems during adolescence are risk factors
      for psychiatric disorders in adulthood.

PMID- 11532797
TI  - The Maudsley long-term follow-up of child and adolescent depression. 1.
      Psychiatric outcomes in adulthood.
AB  - BACKGROUND: Strong links exist between juvenile and adult depression but comorbid
      conduct disorder in childhood may mitigate this continuity. AIMS: To test the
      impact of comorbid conduct disorder on psychiatric adult outcomes. METHOD: A
      group of 149 subjects assessed at the Maudsley Hospital in the period 1970-1983
      and meeting DSM-IV criteria for major depressive disorder with (n=53) or without
      (n=96) conduct disorder were interviewed 20 years later. Data were collected on
      the lifetime history of psychiatric disorders. RESULTS: Adult depressive
      recurrence was high for major depression (62.4%) and any depression (75.2%), and
      survival analyses showed no difference between the two groups. The group with
      conduct disorders had higher rates of drug misuse and dependence, alcoholism and
      antisocial personality disorders. CONCLUSIONS: Adolescent depression carries an
      elevated risk of adult depression irrespective of comorbidity. Comorbid conduct
      disorder in childhood is associated with raised rates of other psychiatric
      outcomes.

PMID- 11532798
TI  - The Maudsley long-term follow-up of child and adolescent depression. 2.
      Suicidality, criminality and social dysfunction in adulthood.
AB  - BACKGROUND: Strong links exist between juvenile and adult depression, but
      comorbid conduct disorder may be associated with worse adult social difficulties.
      AIMS: To test the impact of comorbid conduct disorder on social adjustment and
      dysfunction, suicidality and criminality of adults who had had depression as
      youths. METHOD: Subjects (n=149) assessed at the Maudsley Hospital in 1970-1983
      and meeting DSM-IV criteria for major depressive disorder with (CD-MDD; n=53) or
      without (MDD; n=96) conduct disorder were interviewed 20 years later. Data were
      collected on lifetime psychiatric disorders and adult social/personality
      functioning. Death certificates and criminal records were obtained. RESULTS: The
      suicide risk was 2.45%, and 44.3% of the sample had attempted suicide once in
      their lives. Compared with the MDD group, the CD-MDD group had higher rates of
      suicidal behaviours and criminal offences, and exhibited more pervasive social
      dysfunction. CONCLUSIONS: Adolescent depression is associated with raised risks
      of adult suicidality and with persistent interpersonal difficulties. Youths with
      CD-MDD show more severe and pervasive social dysfunction.

PMID- 11532799
TI  - Examining the comorbidity of ADHD-related behaviours and conduct problems using a
      twin study design.
AB  - BACKGROUND: Although attention-deficit hyperactivity disorder (ADHD) and conduct
      disorder (CD) frequently co-occur, the underlying mechanisms for this comorbidity
      are not well understood. AIMS: To examine whether ADHD and conduct problems share
      common risk factors and whether ADHD+CD is a more heritable variant of ADHD.
      METHOD: Questionnaires were sent to 2846 families. Parent-rated data were
      obtained for 2082 twin pairs and analysed using bivariate genetic analysis and a
      liability threshold model approach. RESULTS: The overlap of ADHD and conduct
      problems was explained by common genetic and non-shared environmental factors
      influencing both categories. Nevertheless, the two categories appeared to be
      partly distinct in that additional environmental factors influenced conduct
      problems. It appeared that ADHD+CD was a genetically more severe variant of ADHD.
      CONCLUSIONS: Conduct problems and ADHD share a common genetic aetiology; ADHD+CD
      appears to be a more severe subtype in terms of genetic loading as well as
      clinical severity.

PMID- 11532800
TI  - Child psychiatric symptoms and psychosocial impairment: relationship and
      prognostic significance.
AB  - BACKGROUND: Relatively little is known about the relationships between
      psychiatric symptoms, diagnosis and psychosocial impairment. AIMS: To examine
      these contemporaneous relationships and prognostic significance in a large
      general population sample. METHOD: Symptoms of major depression, conduct and
      oppositional defiant disorders were assessed by interview in two waves of the
      Virginia Twin Study of Adolescent behavioural Development (2800 children aged 8
      16 years). RESULTS: Many children below the DSM-III-R diagnostic threshold,
      especially for depression, had symptom-related impairment, whereas many children
      reaching the symptom threshold for conduct and oppositional defiant disorders
      were little impaired. Impairment score was linearly related to symptom count,
      with no evidence of any additional impairment at the diagnostic threshold. For
      depression, only symptoms predicted later symptoms and diagnosis. For conduct and
      oppositional defiant disorders, impairment was additionally predictive of later
      symptoms and diagnosis. CONCLUSIONS: Impairment, in addition to symptoms, is
      important for both nosology and prognosis.

PMID- 11532801
TI  - Development of weight and shape concerns in the aetiology of eating disorders.
AB  - BACKGROUND: Although weight and shape concerns are considered to be integral to
      the psychopathology of anorexia and bulimia nervosa, uncertainties remain about
      developmental aspects of the aetiology of these concerns and their relationship
      to eating disorders. AIMS: To review the recent literature on weight and shape
      concern, with particular emphasis on aetiology, to identify a possible
      developmental pathway from weight concern through abnormal eating behaviour to
      disorder. METHOD: Literature review of Medline and Psychlit databases using the
      keywords 'eating disorder', 'weight concern', 'shape concern' and 'aetiology'.
      Inclusion criteria were based on the strength of quantitative research findings,
      originality of ideas and recent publication. RESULTS: Weight and shape concerns
      follow a developmental pathway arising before the typical age for the development
      of eating disorders. The origins are multifactorial, with biological, family and
      sociocultural features predominating. CONCLUSIONS: Although weight and shape
      concern seems commonly to underlie the development of eating disorders, an
      alternative pathway appears to exist through impulsivity and fear of loss of
      control. Prevention strategies may usefully focus on the attitudes and concerns
      that lead to dieting behaviour.

PMID- 11532802
TI  - Possible role of cortisol and dehydroepiandrosterone in human development and
      psychopathology.
AB  - BACKGROUND: The characteristics of adrenal hormone secretion change markedly
      during infancy. Disturbances in basal levels may precipitate psychological
      dysfunction and are associated with psychopathology in young people. AIMS: To
      relate three aspects of behavioural endocrinology: developmental changes in
      cortisol and dehydroepiandrosterone (DHEA), the role of these hormones in the
      psychopathology of young people, and the action of these steroids in the brain.
      METHOD: A selective review from the human developmental, psychiatric and
      neurosciences literature. RESULTS: There are developmentally mediated changes in
      brain sensitivity following excess exposure to cortisol. This may result in
      impairments of mental and behavioural function. DHEA and gonadal steroids may
      modulate the actions of cortisol. CONCLUSIONS: Steroid hormones contribute to
      shaping behavioural function during early development and act as risk factors for
      psychopathology.

PMID- 11532803
TI  - Prevalence of dementia according to DSM-III-R and ICD-10: results of the Leipzig
      Longitudinal Study of the Aged (LEILA75+) Part 1.
AB  - BACKGROUND: The prevalence of dementia diagnosis according to ICD-10 and DSM-III
      R in population surveys remains poorly understood. AIMS: To report and compare
      prevalence rates according to DSM-III-R and ICD-10. METHOD: A population-based
      sample (n=1692, age 75+years) was investigated by a Structured Interview for
      Diagnosis of Dementia of Alzheimer Type, Multiinfarct Dementia and Dementia of
      other Aetiology according to DSM-III-R and ICD-10 (SIDAM). RESULTS: Whereas 17.4%
      (95% CI=15.9-19.5) of individuals aged 75+ years suffer from dementia according
      to DSM-III-R, only 12.4% (95% CI=10.6-14.2) are diagnosed as having dementia
      according to ICD-10. The results revealed lower ICD-10 rates in all investigated
      age groups. The largest differences appear in the oldest of the elderly.
      CONCLUSIONS: The ICD-10 sets a higher threshold for dementia diagnosis. Larger
      differences in the eldest age groups might reflect difficulties in applying case
      definitions, especially in those beyond 90 years old.

PMID- 11532804
TI  - Incidence of dementia according to DSM-III-R and ICD-10: results of the Leipzig
      Longitudinal Study of the Aged (LEILA75+), Part 2.
AB  - BACKGROUND: The impact of different case definitions on incidence rates remains
      unclear. AIMS: To compare incidence rates of dementia according to DSM-III-R and
      ICD-10. METHOD: A two-wave community study was conducted (n=1692, age 75+ years
      follow-up period 1.6 years). Cognitive function was assessed by the Structured
      Interview for Diagnosis of Dementia of Alzheimer Type, Multiinfarct Dementia and
      Dementia of other Aetiology according to ICD-10 and DSM-III-R (SIDAM). RESULTS:
      The annual incidence rate for dementia by applying different case definitions was
      found to be quite similar (DSM-III-R: 47.4 (95% CI=36.1-61.2) per 1000 person
      years; ICD-10: 45.8 (95% CI=35.0-59.0) per 1000 person-years). Age-specific
      incidence rates increase steeply with age. CONCLUSIONS: The impact of different
      case definitions on incidence rates of dementia appears limited if case
      definitions and case-finding procedures at baseline and follow-up are applied
      consistently.

PMID- 11532805
TI  - Costs of dementia in England and Wales in the 21st century.
AB  - BACKGROUND: An important factor determining future health care expenditure is the
      relationship between ageing, health status and development of age-related
      disorders such as dementia. AIMS: To estimate the formal care costs associated
      with dementia in England and Wales between 1994 and 2031. METHOD: Epidemiological
      cost model, applied to individuals aged 65 years or over with dementia, using
      estimates of life expectancy with dementia and dementia-free life expectancy.
      RESULTS: Total costs per year were pound 0.95 billion (men) and pound 5.35
      billion (women) using 1994 population estimates. For 2031, costs were pound 2.34
      billion and pound 11.20 billion, respectively. Reduced dementia prevalence rates
      and improvements in mental and physical functioning resulted in lower estimates:
      pound 1.01 billion (men) and pound 5.77 billion (women), and pound 1.65 billion
      (men) and pound 7.87 billion (women), respectively. CONCLUSIONS: Future increases
      in the population aged 65 years or over lead to rising formal care costs.
      However, the magnitude of cost changes depends on assumptions over dementia
      prevalence and levels of mental and physical functioning.

PMID- 11532806
TI  - A defence of evolutionary psychology.

PMID- 11532807
TI  - A defence of evolutionary psychology.

PMID- 11532808
TI  - Evidence-based psychiatry within multi-disciplinary clinical teams.

PMID- 11532809
TI  - A defence of community mental health teams.

PMID- 11532810
TI  - Methodological rigour in cross-cultural research.

PMID- 11532811
TI  - Light therapy for seasonal affective disorder: a type II error.

PMID- 11532812
TI  - Pragmatic approach to the dangers of cannabis use.

PMID- 11532813
TI  - Chromosome 22q11 deletion and brain structure.

PMID- 11532815
TI  - Future of mental health services in Kosovo.

PMID- 11532814
TI  - Suicide prevention: service contacts and coordination between primary and
      secondary care.

PMID- 11532816
TI  - The improper use of asylums for the insane. 1900.

PMID- 11532817
TI  - Liaison psychiatry.

PMID- 11532819
TI  - Optimising antidepressant use in clinical practice: towards criteria for
      antidepressant selection.
AB  - BACKGROUND: Current treatment for depression in primary care and other out
      patient settings demonstrates a pattern that is incongruous with the magnitude of
      the burden of depression suggested by its associated disability. AIMS: To review
      important considerations in current depression treatment with a focus on
      antidepressant use. METHOD: Factors influencing the undertreatment of depression
      in real-world settings are examined. RESULTS: Patient and clinician behaviour as
      well as the incentives created by the health care system affect the likelihood of
      realising effective antidepressant therapy in practice. CONCLUSIONS: Given the
      complexities of clinical practice, selection criteria for an antidepressant
      should include safety, efficacy and tolerability, as well as the ability of the
      antidepressant to deliver real-world efficacy while balancing health care costs
      in the long term.

PMID- 11532820
TI  - Clinical importance of long-term antidepressant treatment.
AB  - BACKGROUND: Depression, which only a few decades ago was considered to be a short
      term illness requiring short-term treatment, is now recognised as a recurrent,
      sometimes chronic, long-term illness. AIMS: To highlight the clinical importance
      of long-term antidepressant therapy in the treatment of depression. METHOD: The
      current literature was reviewed to examine the relationship between duration of
      antidepressant therapy and efficacy. RESULTS: Approximately one-third to a half
      of patients successfully stabilised in acute-phase treatment will relapse if
      medication is not sustained throughout the continuation period. Only 10-15% will
      relapse if medication is continued. For maintenance-phase therapy, approximately
      60% of patients at risk will experience a recurrent episode of depression within
      1 year if untreated, whereas those who continue in treatment will have a
      recurrence rate of between 10% and 30%. CONCLUSIONS: Risk of relapse and
      recurrence of depression can be significantly reduced if adequate continuation
      and maintenance therapy durations are achieved.

PMID- 11532821
TI  - Antidepressant use in clinical practice: efficacy v. effectiveness.
AB  - BACKGROUND: Although the efficacy of antidepressants has been demonstrated in
      randomised, controlled clinical trials, it is how an antidepressant is used in
      clinical practice that determines its clinical effectiveness, or real-world
      efficacy. AIMS: To explore the frequency with which antidepressants are used at
      adequate dose and duration to obtain remission of symptoms and prevent relapse in
      clinical practice and discuss potential implications for clinical outcomes.
      METHOD: Studies of antidepressant prescribing were reviewed and comparisons made
      between antidepressant classes and individual compounds within those classes.
      RESULTS: Naturalistic studies show that patients who begin therapy on tricyclic
      antidepressants often receive sub-therapeutic doses for inadequate duration;
      conversely, patients who begin therapy on selective serotonin reuptake inhibitors
      more often receive an adequate dose of therapy for a longer duration.
      CONCLUSIONS; How antidepressants are used in clinical practice can determine the
      clinical outcomes that are achieved. Antidepressants that are more forgiving of
      sub-optimal prescribing and use patterns by providers and patients, respectively,
      may help to improve real-world efficacy.

PMID- 11532822
TI  - Antidepressant selection and economic outcome: a review of methods and studies
      from clinical practice.
AB  - BACKGROUND: Economic considerations increasingly play a role in the selection of
      antidepressant drugs and are often based on analyses from prospective and
      retrospective studies. However, the non-randomisation found in retrospective
      studies may result in significant selection bias. AIMS: To highlight the use of
      statistical methods in non-randomised studies and the application of those
      methods to economic analyses. METHOD: The literature on the observational studies
      of economic outcomes with alternative antidepressants is reviewed and several
      statistical methodologies to control for biases that can occur in non-randomised
      study designs are described. RESULTS: In comparisons of antidepressant drugs,
      differences in acquisition costs are consistently found to be at least offset by
      other components of care when broad measures of health care resource utilisation
      are considered. CONCLUSIONS: Economic evaluations of antidepressants should be
      based on broad measures of health care expenditure and can rely on data generated
      in real-world settings if appropriate statistical methods are used to control for
      the potential biases of non-randomisation.

PMID- 11532823
TI  - Private health care in developing countries.

PMID- 11532824
TI  - Cardiovascular complications of recreational drugs.

PMID- 11532826
TI  - The safety of acupuncture.

PMID- 11532825
TI  - A key medical decision maker: the patient.

PMID- 11532827
TI  - Ireland fears blood shortage with new ban on donors.

PMID- 11532830
TI  - Drug company breaks 30 year agreement on patient advertising.

PMID- 11532831
TI  - Dutch consider following UK on vaccines after meningitis scare.

PMID- 11532832
TI  - German company offers "package deal ops" to Ireland.

PMID- 11532833
TI  - COX 2 inhibitors may increase risk of heart attack.

PMID- 11532835
TI  - Leading the resistance. Interview by Geoff Watts.

PMID- 11532836
TI  - Prevalence of Gulf war veterans who believe they have Gulf war syndrome:
      questionnaire study.
AB  - OBJECTIVES: To determine how many veterans in a random sample of British veterans
      who served in the Gulf war believe they have "Gulf war syndrome," to examine
      factors associated with the presence of this belief, and to compare the health
      status of those who believe they have Gulf war syndrome with those who do not.
      DESIGN: Questionnaire study asking British Gulf war veterans whether they believe
      they have Gulf war syndrome and about symptoms, fatigue, psychological distress,
      post-traumatic stress, physical functioning, and their perception of health.
      PARTICIPANTS: 2961 respondents to questionnaires sent out to a random sample of
      4250 Gulf war veterans (69.7%). MAIN OUTCOME MEASURE: The proportion of veterans
      who believe they have Gulf war syndrome. RESULTS: Overall, 17.3% (95% confidence
      interval 15.9 to 18.7) of the respondents believed they had Gulf war syndrome.
      The belief was associated with the veteran having poor health, not serving in the
      army when responding to the questionnaire, and having received a high number of
      vaccinations before deployment to the Gulf. The strongest association was knowing
      another person who also thought they had Gulf war syndrome. CONCLUSIONS:
      Substantial numbers of British Gulf war veterans believe they have Gulf war
      syndrome, which is associated with psychological distress, a high number of
      symptoms, and some reduction in activity levels. A combination of biological,
      psychological, and sociological factors are associated with the belief, and these
      factors should be addressed in clinical practice.

PMID- 11532837
TI  - Teenage pregnancy and risk of adverse perinatal outcomes associated with first
      and second births: population based retrospective cohort study.
AB  - OBJECTIVE: To determine whether first and second births among teenagers are
      associated with increased risk of adverse perinatal outcomes after confounding
      variables have been taken into account. DESIGN: Population based retrospective
      cohort study using routine discharge data for 1992-8. SETTING: Scotland. MAIN
      OUTCOME MEASURES: Stillbirth, preterm delivery, emergency caesarean section, and
      small for gestational age baby among non-smoking mothers aged 15-19 and 20-29.
      RESULTS: The 110 233 eligible deliveries were stratified into first and second
      births. Among first births, the only significant difference in adverse outcomes
      by age group was for emergency caesarean section, which was less likely among
      younger mothers (odds ratio 0.5, 95% confidence interval 0.5 to 0.6). Second
      births in women aged 15-19 were associated with an increased risk of moderate
      (1.6, 1.2 to 2.1) and extreme prematurity (2.5, 1.5 to 4.3) and stillbirth (2.6,
      1.3 to 5.3) but a reduced risk of emergency caesarean section (0.7, 0.5 to 1.0).
      CONCLUSIONS: First teenage births are not independently associated with an
      increased risk of adverse pregnancy outcome and are at decreased risk of delivery
      by emergency caesarean section. However, second teenage births are associated
      with an almost threefold risk of preterm delivery and stillbirth.

PMID- 11532838
TI  - Does bullying cause emotional problems? A prospective study of young teenagers.
AB  - OBJECTIVES: To establish the relation between recurrent peer victimisation and
      onset of self reported symptoms of anxiety or depression in the early teen years.
      DESIGN: Cohort study over two years. SETTING: Secondary schools in Victoria,
      Australia. PARTICIPANTS: 2680 students surveyed twice in year 8 (aged 13 years)
      and once in year 9. MAIN OUTCOME MEASURES: Self reported symptoms of anxiety or
      depression were assessed by using the computerised version of the revised
      clinical interview schedule. Incident cases were students scoring >/=12 in year 9
      but not previously. Prior victimisation was defined as having been bullied at
      either or both survey times in year 8. RESULTS: Prevalence of victimisation at
      the second survey point in year 8 was 51% (95% confidence interval 49% to 54%),
      and prevalence of self reported symptoms of anxiety or depression was 18% (16% to
      20%). The incidence of self reported symptoms of anxiety or depression in year 9
      (7%) was significantly associated with victimisation reported either once (odds
      ratio 1.94, 1.1 to 3.3) or twice (2.30, 1.2 to 4.3) in year 8. After adjustment
      for availability of social relations and for sociodemographic factors, recurrent
      victimisation remained predictive of self reported symptoms of anxiety or
      depression for girls (2.60, 1.2 to 5.5) but not for boys (1.36, 0.6 to 3.0).
      Newly reported victimisation in year 9 was not significantly associated with
      prior self report of symptoms of anxiety or depression (1.48, 0.4 to 6.0).
      CONCLUSION: A history of victimisation and poor social relationships predicts the
      onset of emotional problems in adolescents. Previous recurrent emotional problems
      are not significantly related to future victimisation. These findings have
      implications for how seriously the occurrence of victimisation is treated and for
      the focus of interventions aimed at addressing mental health issues in
      adolescents.

PMID- 11532839
TI  - Prescribing of drugs for use outside their licence in palliative care: survey of
      specialists in the United Kingdom.

PMID- 11532840
TI  - Adverse events following acupuncture: prospective survey of 32 000 consultations
      with doctors and physiotherapists.

PMID- 11532841
TI  - The York acupuncture safety study: prospective survey of 34 000 treatments by
      traditional acupuncturists.

PMID- 11532842
TI  - Getting informed consent from patients to take part in the clinical training of
      students: randomised trial of two strategies.

PMID- 11532843
TI  - Drug points: Hypersensitivity reaction to balsalazide.

PMID- 11532844
TI  - Randomised controlled trial of an interactive multimedia decision aid on hormone
      replacement therapy in primary care.
AB  - OBJECTIVE: To determine whether a decision aid on hormone replacement therapy
      influences decision making and health outcomes. DESIGN: Randomised controlled
      trial. SETTING: 26 general practices in the United Kingdom. PARTICIPANTS: 205
      women considering hormone replacement therapy. INTERVENTION: Patients' decision
      aid consisting of an interactive multimedia programme with booklet and printed
      summary. OUTCOME MEASURES: Patients' and general practitioners' perceptions of
      who made the decision, decisional conflict, treatment choice, menopausal
      symptoms, costs, anxiety, and general health status. RESULTS: Both patients and
      general practitioners found the decision aid acceptable. At three months, mean
      scores for decisional conflict were significantly lower in the intervention group
      than in the control group (2.5 v 2.8; mean difference -0.3, 95% confidence
      interval -0.5 to -0.2); this difference was maintained during follow up. A higher
      proportion of general practitioners perceived that treatment decisions had been
      made "mainly or only" by the patient in the intervention group than in the
      control group (55% v 31%; 24%, 8% to 40%). At three months a lower proportion of
      women in the intervention group than in the control group were undecided about
      treatment (14% v 26%; -12%, -23% to -0.4%), and a higher proportion had decided
      against hormone replacement therapy (46% v 32%; 14%, 1% to 28%); these
      differences were no longer apparent by nine months. No differences were found
      between the groups for anxiety, use of health service resources, general health
      status, or utility. The higher costs of the intervention were largely due to the
      video disc technology used. CONCLUSIONS: An interactive multimedia decision aid
      in the NHS would be popular with patients, reduce decisional conflict, and let
      patients play a more active part in decision making without increasing anxiety.
      The use of web based technology would reduce the cost of the intervention.

PMID- 11532845
TI  - Randomised controlled trial of an interactive multimedia decision aid on benign
      prostatic hypertrophy in primary care.
AB  - OBJECTIVE: To determine whether a decision aid on benign prostatic hypertrophy
      influences decision making, health outcomes, and resource use. DESIGN: Randomised
      controlled trial. SETTING: 33 general practices in the United Kingdom.
      PARTICIPANTS: 112 men with benign prostatic hypertrophy. INTERVENTION: Patients'
      decision aid consisting of an interactive multimedia programme with booklet and
      printed summary. OUTCOME MEASURES: Patients' and general practitioners'
      perceptions of who made the decision, decisional conflict scores, treatment
      choice and prostatectomy rate, American Urological Association symptom scale,
      costs, anxiety, utility, and general health status. RESULTS: Both patients and
      general practitioners found the decision aid acceptable. A higher proportion of
      patients (32% v 4%; mean difference 28%, 95% confidence interval 14% to 41%) and
      their general practitioners (46% v 25%; 21%, 3% to 40%) perceived that treatment
      decisions had been made mainly or only by patients in the intervention group
      compared with the control group. Patients in the intervention group had
      significantly lower decisional conflict scores than those in the control group at
      three months (2.3 v 2.6; -0.3, -0.5 to -0.1, P<0.01) and this was maintained at
      nine months. No differences were found between the groups for anxiety, general
      health status, prostatic symptoms, utility, or costs (excluding costs associated
      with the video disc equipment). CONCLUSIONS: The decision aid reduced decisional
      conflict in men with benign prostatic hypertrophy, and the patients played a more
      active part in decision making. Such programmes could be delivered cheaply by the
      internet, and there are good arguments for coordinated investment in them,
      particularly for conditions in which patient utilities are important.

PMID- 11532846
TI  - Fortnightly review: Beneficial effects of potassium.

PMID- 11532847
TI  - Lesson of the week: Recurrent bacterial meningitis: the need for sensitive
      imaging.

PMID- 11532848
TI  - Globalisation is good for your health, mostly.

PMID- 11532849
TI  - Regulating nursing homes: Residential nursing facilities in the United States.

PMID- 11532852
TI  - Counteracting spontaneous transformation via overexpression of rate-limiting DNA
      base excision repair enzymes.
AB  - DNA damage of endogenous origin may significantly contribute to human cancer. A
      major pathway involved in DNA repair of endogenous damage is DNA base excision
      repair (BER). BER is rather efficient in human cells but a certain amount of
      endogenous damage inevitably escapes mending and likely contributes to human
      carcinogenesis. Apart from some glycosylases that are particularly sluggish (e.g.
      8-oxoG DNA glycosylase), recent work suggests that the general rate-limiting
      steps of BER may be trimming of 2-deoxyribose 5-phosphate in case the process is
      started by a monofunctional glycosylase or trimming of a 3'-blocking fragment, in
      case BER is started by a bifunctional glycosylase or in the case of single-strand
      breaks produced by free radical attack. Overexpression of the 5'
      deoxyribophosphodiesterase (dRPase) domain of DNA polymerase beta, on the one
      hand, and of yeast APN1 protein, containing an efficient 3' repair activity, on
      the other, may lead to improved BER in mammals. The recently characterized S3
      protein of Drosophila, containing both dRPase and 3'-trimming activities, could
      also be considered for overexpression studies. The possible protecting role of
      enhanced BER could be investigated in cultured rodent embryonic fibroblasts
      undergoing spontaneous transformation, a most interesting system that merits
      rediscovery.

PMID- 11532853
TI  - Outcome in prostate cancer associations with skin type and polymorphism in
      pigmentation-related genes.
AB  - Epidemiological studies have suggested that UV exerts a protective effect on
      prostate cancer. Accordingly, we determined, in 210 prostate cancer cases,
      whether parameters of exposure, skin type and polymorphism in MC1R, VDR and TYR
      were associated with the outcome parameters, histological grade, clinical stage
      and presence of bone metastases. We used logistic regression analysis, with
      correction for age and metastases, stage and grade in the models, to determine if
      the frequencies of individual factors were different in the patient groups. The
      development of metastases was not associated with UV exposure parameters.
      Paradoxically, patients with skin type 1 were at significantly reduced risk [P =
      0.027, odds ratio (OR) 0.17, 95% CI 0.03-0.82] of developing metastases compared
      with cases with skin type 4. MC1R Val92/Val92 and VDR ff were associated with
      increased risk of metastases (ORs 4.30 and 4.98, respectively). Further,
      cumulative exposure (P = 0.005, OR 0.85/year) and increasing proportion of
      outdoor occupation (P = 0.001, OR 0.84/unit) were associated with reduced risk of
      advanced stage tumours. Skin types, MC1R or VDR genotypes were not significantly
      associated with advanced stage. None of the exposure parameters, skin types or
      genotypes were associated with tumour grade. While MC1R Val92/Val92 and VDR ff
      were only associated with bone metastases, TYR genotypes were associated with
      each of the outcome parameters. Thus, in logistic regression models that included
      age, but not advanced stage and high grade histology, TYR A1A2 was significantly
      associated with reduced risk of metastases (P = 0.033, OR 0.41). Similarly, in
      models that included age but not the other outcome parameters, associations
      between TYR A2A2 and high-grade and advanced stage were significant (P = 0.040,
      OR 0.41) or approached significance (P = 0.052, OR 0.44), respectively. These
      data indicate for the first time that pigmentation response to UV is associated
      with outcome in prostate cancer.

PMID- 11532854
TI  - 12-Lipoxygenase inhibition induced apoptosis in human gastric cancer cells.
AB  - Arachidonic acid release from membrane phospholipids is essential for tumour cell
      proliferation. Lipoxygenases constitute a pathway for arachidonate metabolism.
      The present study investigated the expression of 12-lipoxygenase and its effect
      on cell proliferation as well as survival in two human gastric cancer cell lines
      (AGS and MKN-28). RT-PCR and western blots, respectively, showed 12-LOX mRNA and
      protein expression in both AGS and MKN-28 cell lines. Treatment with a 12-LOX
      inhibitor, baicalein, significantly inhibited cancer cell proliferation, but a
      metabolite of 12-LOX activity, 12 hydroxyeicosatetraenoic acid (12-HETE) reversed
      baicalein-induced growth inhibition. Furthermore, the blockade of the 12-LOX
      pathway through a 12-LOX inhibitor and antisense induced apoptosis of gastric
      cancer cell lines. The biochemical characteristics of apoptosis were p53
      independent combined with a decrease in bcl-2 expression. Caspase-7 was
      proteolytically activated and responsible for the apoptosis execution.

PMID- 11532855
TI  - OGG1 protein suppresses G:C-->T:A mutation in a shuttle vector containing 8
      hydroxyguanine in human cells.
AB  - 8-Hydroxyguanine (8-OHG) is an oxidatively damaged mutagenic base which causes
      G:C-->T:A transversions in DNA. OGG1 was cloned as a human gene encoding a DNA
      glycosylase that specifically excises 8-OHG from DNA in vitro. However, it was
      not clear whether OGG1 protein suppresses G:C-->T:A transversions caused by 8-OHG
      in human cells in vivo. In the present study we have examined the ability of OGG1
      protein to suppress G:C-->T:A transversions caused by 8-OHG in human cells by
      bacterial suppressor tRNA (supF) forward mutation assay using a shuttle vector
      DNA, pMY189. Introduction of a single 8-OHG residue at position 159 of the supF
      gene in plasmid pMY189 resulted in a 130-fold increase in mutation frequency
      compared with untreated plasmid pMY189 after replication in the NCI-H1299 human
      lung cancer cell line. G:C-->T:A transversions at position 159 were detected in
      >90% of the supF mutants from the 8-OHG-containing plasmid. The mutation
      frequency of the 8-OHG-containing plasmid was significantly reduced by
      overexpression of OGG1 protein in NCI-H1299 cells and, in particular, the
      occurrence of G:C-->T:A transversion at position 159 in the supF gene was
      suppressed. Furthermore, frequencies and spectra of mutations of the untreated
      pMY189 plasmid did not differ significantly with overexpression of OGG1 protein.
      These results indicate that OGG1 protein has the ability to suppress G:C-->T:A
      transversions caused by 8-OHG in human cells in vivo.

PMID- 11532856
TI  - Hepatocyte growth factor signalling stimulates hypoxia inducible factor-1 (HIF-1)
      activity in HepG2 hepatoma cells.
AB  - Hepatocyte growth factor (HGF), a multifunctional cytokine of mesenchymal origin,
      activates the DNA binding of hypoxia inducible factor-1 (HIF-1) in the HepG2 cell
      line: the activated complex contained the inducible alpha subunit. An increased
      expression of HIF-1alpha (mRNA and nuclear protein levels) was observed. To
      investigate the molecular basis of the HIF-1 response under this non-hypoxic
      condition, we evaluated first the expression of putative target genes. We found a
      time-dependent increase in steady-state mRNA levels of heme oxygenase and
      urokinase plasminogen activator at 4 h, followed by that of urokinase receptor at
      10 h. The enhanced expression of these genes might confer the invasive phenotype,
      since HGF is a proliferative and scatter factor. Second, we examined some aspects
      of HIF-1 activity regulation in HGF-treated cells with the following findings:
      (i) the activation of HIF-1 DNA binding was prevented by proteasome blockade,
      probably because stabilization of the cytosolic alpha-subunit protein level is
      not sufficient to generate a functional form: also under these conditions nuclear
      protein level of HIF-1alpha did not increase; (ii) N-acetylcysteine, a free
      radical scavenger, strongly decreased HIF-1 activation suggesting a role of
      reactive oxygen species in this process; (iii) the thiol reducing agent
      dithiothreitol was ineffective. Third, consistent with these data, N
      acetylcysteine reduced the stimulatory effect of HGF on stress kinase activities,
      while p42/44 mitogen activated kinase (MAPK) was unmodified, suggesting an
      involvement of c-Jun-N-terminal kinase (JNK) and p38 MAPK in HIF-1 activation.
      Finally, LY 294002 induced the blockade of phosphatidylinositol 3-kinase (PI3K),
      one of the principal transducers of HGF/Met receptor signalling, prevented the
      enhancement of HIF-1 DNA binding and JNK activity, but the inhibition of p42/44
      MAPK phosphorylation with PD 98059 was ineffective. In conclusion, we suggest
      that HGF triggers a signal transduction cascade involving PI3K and ultimately
      activates HIF-1.

PMID- 11532857
TI  - Dietary N-acetyl-L-cysteine modulates benzo[a]pyrene-induced skin tumors in
      cancer-prone p53 haploinsufficient Tg.AC (v-Ha-ras) mice.
AB  - Epidemiologic studies support the protective role of dietary antioxidants in
      preventing cancer. However, emerging evidence from clinical trials and laboratory
      data suggest that in some cases individual antioxidant supplements may actually
      exacerbate carcinogenesis. Our goal was to explore these paradoxical activities
      in a rodent model that possesses genotypic characteristics of human cancers. We
      selected the p53 haploinsufficient Tg.AC (v-Ha-ras) mouse as a model, because it
      contains an activated, carcinogeninducible ras oncogene and an inactivated p53
      tumor suppressor gene, which are frequent genetic alterations in human cancers.
      These mice develop chemically induced benign and malignant skin tumors rapidly
      which can easily be quantified. Mice were fed basal diets with or without 3% N
      acetyl-L-cysteine (NAC), a well-recognized antioxidant, prior to, during and
      after topical application of the carcinogen benzo[a]pyrene (64 microg/mouse)
      applied twice per week for 7 weeks. Tumor incidence exceeded 90% for both groups,
      and NAC did not reduce tumor latency. Mice fed NAC displayed a 43% reduction (P <
      0.05) in tumor multiplicity and delayed the appearance of lesions (P < 0.05).
      Dietary NAC also significantly (P < 0.05) improved group survival by 5 weeks.
      Total tumor yields were reduced in both dietary groups but malignant spindle cell
      tumors (SCT) increased by 25% in NAC-fed mice. The v-Ha-ras oncogene and p53
      protein products were clearly co-expressed in both benign and malignant lesions
      from both dietary groups. In summary, dietary supplementation with NAC was
      chemopreventive, but the marginal increase in SCT suggests a paradoxical effect.

PMID- 11532858
TI  - Activation of the PPAR pathway induces apoptosis and COX-2 inhibition in HT-29
      human colon cancer cells.
AB  - The gamma isoform of the peroxisome proliferator-activated receptor (PPARgamma)
      is a nuclear receptor that regulates adipocyte differentiation. Recently it has
      been shown to be expressed in human colonic mucosa and cancer, but its role in
      colon carcinogenesis and progression is still unclear. We demonstrate that
      activation of PPARgamma by ciglitazone (cig), a selective PPARgamma ligand,
      induces HT-29 human colon cancer cells to undergo apoptosis. Treatment with cig
      also down-regulates expression of cyclooxygenase-2 (COX-2) protein. Simultaneous
      exposure of cells to cig and 9-cis-retinoic acid (9-cis-RA), a ligand for
      retinoid X receptor, results in an increased apoptotic effect and increased
      inhibition of COX-2 expression, compared with cells treated with either cig or 9
      cis-RA alone. As COX-2 is overexpressed in human colon cancer and has been
      implicated in augmenting invasiveness and tumorigenecity, the ability of
      PPARgamma activation to decrease COX-2 expression and induce apoptosis suggests
      that the PPARgamma pathway may be considered as a therapeutic target for colon
      cancer.

PMID- 11532859
TI  - ras oncogene expression determines sensitivity for intercellular induction of
      apoptosis.
AB  - Fibroblasts carrying an inducible ras oncogene acquire the transformed phenotype
      after oncogene induction. As a consequence, the transformed cells become
      sensitive to intercellular induction of apoptosis, a novel regulatory process
      directed by non-transformed fibroblasts against their transformed descendants.
      The causal relationship between oncogene expression and sensitivity to
      intercellular induction of apoptosis is based on extracellular superoxide anion
      production by oncogene-expressing cells. Superoxide anions (after dismutation to
      hydrogen peroxide) thereby foster HOCl synthesis and at the same time direct the
      selectivity of apoptosis induction through hydroxyl generation from HOCl. In
      parallel, ras expression enhances the sensitivity of fibroblasts for apoptosis
      inducing stimuli like cycloheximide, ceramide and mitomycin C. This sensitization
      seems to be based on a decreased concentration of short lived endogenous
      apoptosis inhibitors. TGF-beta, like ras induction, decreases the concentration
      of endogenous apoptosis inhibitors, but does not induce the transformed
      phenotype. Therefore, TGF-beta treatment alone is not sufficient to render
      fibroblasts sensitive for intercellular induction of apoptosis, but TGF-beta
      treatment in parallel with ras activation enhances intercellular induction of
      apoptosis. Our findings demonstrate that Ras-mediated superoxide anion production
      determines sensitivity to intercellular induction of apoptosis, whereas the
      parallel decrease in endogenous apoptosis inhibitors modulates the kinetics of
      apoptosis induction.

PMID- 11532860
TI  - Non-steroidal anti-inflammatory drugs induce apoptosis in gastric cancer cells
      through up-regulation of bax and bak.
AB  - Aspirin- and non-steroidal anti-inflammatory drug (NSAID)-induced apoptosis is
      one of the important mechanisms for their anti-tumour effect in gastric cancer.
      We aimed at determining the role of bcl-2 family proteins and caspases in the
      apoptotic process. Gastric cancer cell lines AGS (wild-type p53) and MKN-28
      (mutant p53) were used. Cell proliferation was measured by MTT assay. Apoptosis
      was determined by acridine orange staining. Protein expressions were determined
      by western blotting. Aspirin and indomethacin inhibited cell proliferation and
      induced apoptosis in both cells. AGS cells were more sensitive compared with MKN
      28 cells. The pro-apoptotic proteins bax and bak were overexpressed after
      treatment, while the protein level of bcl-2 remained unchanged. Apoptosis was
      accompanied by an increase in caspase-3 activity and cleavage of caspase-3 and
      poly(ADP-ribose) polymerase. Inhibition of caspase-3 rescued aspirin-induced
      apoptosis. Our results suggest that one of the major pathways which mediates the
      anti-tumour response of aspirin and indomethacin in gastric cancer cells is
      through up-regulation of bax and bak and activation of caspase-3. Bax and bak are
      important in the chemoprevention of gastric cancer.

PMID- 11532861
TI  - Silymarin inhibits function of the androgen receptor by reducing nuclear
      localization of the receptor in the human prostate cancer cell line LNCaP.
AB  - A number of reports have shown that the polyphenolic flavonoid silymarin (SM) is
      an effective anticancer agent. Agents with novel mechanisms of blocking androgen
      receptor (AR) function may be useful for prostate cancer prevention and therapy.
      Previous studies showed that silibinin (SB), the major active component of SM,
      could inhibit cell proliferation of a human prostate cancer cell line, LNCaP, by
      arresting the cell cycle at the G(1) phase without causing cell death. This study
      further delineates the potential molecular mechanism by which SM and SB exhibit
      antiproliferative effects on androgen-responsive prostate cancer cells by
      inhibiting function of the AR. We observed that SM and SB inhibited androgen
      stimulated cell proliferation as well as androgen-stimulated secretion of both
      prostate-specific antigen (PSA) and human glandular kallikrein (hK2).
      Additionally, for the first time, we show that an immunophilin, FKBP51, is
      androgen regulated and that this up-regulation is suppressed by SM and SB. We
      further demonstrate that transactivation activity of the AR was diminished by SM
      and SB using gene transfer of PSA promoter and hK2 androgen-responsive element
      constructs. However, expression and steroid-binding ability of total AR were not
      affected by SM in western blotting and ligand-binding assays. Intriguingly, we
      found that nuclear AR levels are significantly reduced by SM and SB in the
      presence of androgens using western blotting assay and immunocytochemical
      staining. This study provides a new insight into how SM and SB negatively
      modulate androgen action in prostate cancer cells.

PMID- 11532862
TI  - Real-time PCR analysis of the N-acetyltransferase NAT1 allele *3, *4, *10, *11,
      *14 and *17 polymorphism in squamous cell cancer of head and neck.
AB  - Although tobacco smoke has been established as a main risk factor in the
      development of head and neck squamous cell cancer (HNSCC), genetic polymorphisms
      of xenobiotic metabolizing enzymes are supposed to modulate an individual's
      susceptibility to smoking-related HNSCC. N-acetyltransferase (NAT) 1 gene is
      known to be polymorphic and its protein product is implicated in the activation
      and detoxification of carcinogens, such as aromatic amines, present in tobacco
      smoke. We developed a rapid and reproducible LightCycler-assisted real-time
      polymerase chain reaction (PCR) for NAT1 genotyping, which allowed the parallel
      differentiation of NAT1*3, *4, *10 and *11 alleles and separately of NAT1*14 and
      *17 alleles within 60 min without the need for further post-PCR processing. In
      order to investigate the role of the NAT1 gene polymorphism as a risk-modifying
      factor in HNSCC, we tested for the presence of NAT1*3, *4, *10, *11, *14 and *17
      alleles in a case-control study of 291 HNSCC patients and 300 healthy controls of
      Caucasian origin. Our findings suggest that in Caucasians, the risk of HNSCC is
      not associated with NAT1 polymorphism. The overall distribution of NAT1 allele
      frequencies was not significantly different among cases and controls. The
      presence of the fast acetylator NAT1*10 and NAT1*11 alleles did not significantly
      increase the risk of HNSCC and no modifying effect of NAT1*10 was observed among
      smokers. This new approach in NAT1 genotyping substantially increases throughput
      of sample analysis and, therefore, enhances opportunities to study NAT1 as a risk
      factor in different cancers in large-scale studies.

PMID- 11532863
TI  - Effect of cruciferous vegetable consumption on heterocyclic aromatic amine
      metabolism in man.
AB  - The consumption of cooked meat appears to predispose individuals to colonic
      cancer and heterocyclic aromatic amines (HA), formed during the cooking of meat,
      have been suggested as aetiological agents. Consumption of cruciferous vegetables
      is thought to protect against cancer. To study the effect of cruciferous
      vegetables on heterocyclic aromatic amine metabolism in man, a three-period,
      dietary intervention study has been carried out with 20 non-smoking Caucasian
      male subjects consuming cooked meat meals containing known amounts of these
      carcinogens. A high cruciferous vegetable diet (250 g each of Brussels sprouts
      and broccoli per day) was maintained during period 2 but such vegetables were
      excluded from periods 1 and 3. At the end of each period, subjects consumed a
      cooked meat meal and urinary excretion of the HA 2-amino-3,8-dimethylimidazo(4,5
      f)quinoxaline (MeIQx) and 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP)
      was measured. Following a 12 day period of cruciferous vegetable consumption
      (period 2), induction of hepatic CYP1A2 activity was apparent from changes in the
      kinetics of caffeine metabolism. Excretion of MeIQx and PhIP in urine at the end
      of this period of the study was reduced by 23 and 21%, respectively, compared
      with period 1. This reduction in excretion is probably due to an increase in
      amine metabolism that might be expected given the observed increase in CYP1A2
      activity, since this enzyme has been shown to be primarily responsible for the
      oxidative activation of MeIQx and PhIP in man. In period 2, urinary mutagenicity
      was increased relative to period 1 by 52 and 64% in the absence and presence,
      respectively, of a human liver microsomal activation system, yet no evidence was
      found of PhIP adduction to lymphocyte DNA, a potential biomarker of the
      activation process. After another 12 days without cruciferous vegetables (period
      3 of the study), the kinetics of caffeine metabolism had returned to original
      values but excretion of MeIQx and PhIP was still reduced by 17 and 30%,
      respectively, and urinary mutagenicity (with metabolic activation) was still
      elevated compared with period 1. This prolonged response of amine metabolism to
      the cruciferous vegetable diet, shown especially with PhIP, suggests that enzyme
      systems other than CYP1A2 are involved and affected by a cruciferous vegetable
      diet.

PMID- 11532864
TI  - Inhibition of phorbol ester-induced AP-1-DNA binding, c-Jun protein and c-jun
      mRNA by dietary energy restriction is reversed by adrenalectomy in SENCAR mouse
      epidermis.
AB  - The aim of this study was to determine the effects of 40% dietary energy
      restriction (DER) relative to ad libitum feeding on AP-1-DNA binding and
      expression of c-Jun protein and c-jun mRNA in SENCAR mouse skin treated with
      acetone or 12-O-tetradecanoylphorbol 13-acetate (TPA). The role of the
      glucocorticoid hormone corticosterone (CCS) was investigated by adding CCS or
      vehicle control to the drinking water of adrenalectomized mice. AP-1-DNA binding,
      measured by electrophoretic mobility shift assay, showed that TPA treatment for 4
      h increased AP-1-DNA binding by 2-fold over acetone controls (P < 0.05) and that
      DER reduced basal and TPA-induced AP-1-DNA binding in comparison with ad libitum
      fed groups in sham-operated mice (P < 0.05). TPA treatment increased c-Jun
      protein levels in control fed mice (4-fold) and in DER mice (2-fold) over basal
      levels 4 h post-treatment (P < 0.05). Analyzed over all groups, DER reduced c-Jun
      protein levels (P < 0.01) and this effect was reversed by adrenalectomy. TPA
      induction of c-jun mRNA was also reduced by DER compared with ad libitum fed mice
      (P < 0.05). Adrenalectomy and CCS supplementation demonstrated that the effects
      of DER on AP-1-DNA binding were mediated in part by CCS. Measurement of blood
      plasma CCS concentrations showed that: (i) DER increased CCS 5-fold over ad
      libitum fed mice in sham-operated animals (P < 0.05); (ii) adrenalectomy
      decreased CCS over sham-operated mice (P < 0.05); (iii) TPA treatment had no
      effect on CCS. Blood plasma IGF-I concentrations were unaffected by CCS
      modulation or TPA treatment but were decreased by DER compared with ad libitum
      fed mice (P < 0.05). Thus, dietary energy restriction may inhibit cancer
      mechanistically by reducing overall AP-1 transcription through a process that is
      mediated in part by glucocorticoid hormones.

PMID- 11532865
TI  - Characterization of a vitamin D receptor knockout mouse as a model of colorectal
      hyperproliferation and DNA damage.
AB  - The vitamin D receptor knockout (VDR-KO) mouse presents with a skeletal phenotype
      typical for complete lack of genomic 1,25-dihydroxycholecalciferol effects. Our
      previous data from human colorectal tissue suggest that the steroid hormone and
      its receptor may have protective function against tumour progression. In order to
      investigate the relevance of the vitamin D system for pre-malignant site-directed
      changes in the colon, we characterized the amount and site-specific distribution
      of the VDR along the large intestine in wild-type (WT), heterozygote (HT) and KO
      mice. We also evaluated expression of proliferating cell nuclear antigen (PCNA),
      of cyclin D1 and the levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of
      oxidative stress. In colon ascendens, proliferative cells were dispersed all
      along the crypt and expression levels of all three markers were high in WT mice.
      A decrease of VDR expression did not affect expression significantly. In colon
      descendens, however, fewer proliferative cells were solely located in the lower
      third of the crypt, and an inverse relationship between VDR reduction, PCNA
      positivity and cyclin D1 expression was found in HT and KO mice. In parallel to
      enhanced proliferation a highly significant increase of 8-OHdG positivity
      occurred. Therefore, the sigmoid colon of VDR-KO mice, fed on an appropriate
      lactose/calcium-enriched diet to alleviate impaired calcium homeostasis-related
      phenotypic changes, is an excellent model for investigating induction and
      prevention of pre-malignant changes in one of the hotspots for human colorectal
      cancer incidence.

PMID- 11532866
TI  - XRCC1, XRCC3, XPD gene polymorphisms, smoking and (32)P-DNA adducts in a sample
      of healthy subjects.
AB  - DNA repair genes have an important role in protecting individuals from cancer
      causing agents. Polymorphisms in several DNA repair genes have been identified
      and individuals with non-dramatic reductions in the capacity to repair DNA damage
      are observed in the population, but the impact of specific genetic variants on
      repair phenotype and cancer risk has not yet been clarified. In 308 healthy
      Italian individuals belonging to the prospective European project EPIC, we have
      investigated the relationship between DNA damage, as measured by (32)P-DNA adduct
      levels, and three genetic polymorphisms in different repair genes: XRCC1
      Arg399Gln (exon 10), XRCC3-Thr241Met (exon 7) and XPD-Lys751Gln (exon 23). DNA
      adduct levels were measured as relative adduct level (RAL) per 10(9) normal
      nucleotides by DNA (32)P-post-labelling assay in white blood cells from
      peripheral blood. Genotyping was performed by PCR-RFLP analysis. The XRCC3-241Met
      variant was significantly associated with higher DNA adduct levels, whereas XRCC1
      399Gln and XPD-751Gln were associated with higher DNA adduct levels only in never
      smokers. XRCC3-241Met homozygotes had an average DNA adduct level of 11.44 +/-
      1.48 (+/-SE) compared with 7.69 +/- 0.88 in Thr/Met heterozygotes and 6.94 +/-
      1.11 in Thr/Thr homozygotes (F = 3.206, P = 0.042). Never-smoking XRCC1-399Gln
      homozygotes had an average DNA adduct level of 15.60 +/- 5.42 compared with 6.16
      +/- 0.97 in Gln/Arg heterozygotes and 6.78 +/- 1.10 in Arg/Arg homozygotes (F =
      5.237, P = 0.007). A significant odds ratio (3.81, 95% CI 1.02-14.16) to have DNA
      adduct levels above median value was observed for XPD-751Gln versus XPD-751Lys
      never-smoking homozygotes after adjustment for several confounders. These data
      show that all the analysed polymorphisms could result in deficient DNA repair and
      suggest a need for further investigation into the possible interactions between
      these polymorphisms, smoking and other risk factors.

PMID- 11532867
TI  - Biomarkers of genotoxicity of air pollution (the AULIS project): bulky DNA
      adducts in subjects with moderate to low exposures to airborne polycyclic
      aromatic hydrocarbons and their relationship to environmental tobacco smoke and
      other parameters.
AB  - The levels of bulky DNA adducts were measured by (32)P-post-labelling in
      lymphocytes of 194 non-smoking students living in the city of Athens and the
      region of Halkida, Greece, once in the winter and again in the following summer.
      Personal exposures to particulate-bound polycyclic aromatic hydrocarbons (PAH)
      were significantly higher in Athens subjects during both seasons. There was
      hardly any diagonal radioactive zone in the pattern of DNA adducts observed.
      Highest adduct levels were observed in a sub-group of subjects living in or near
      the Halkida Institute campus, which was located in rural surroundings with a
      minimal burden of urban air pollution. The remaining Halkida subjects had
      intermediate levels, while Athens subjects showed the lowest levels. This trend,
      which was observed over both monitoring seasons, consistently paralleled the
      variation in three markers of exposure to environmental tobacco smoke (ETS),
      namely (i) declared times of exposure to ETS during the 24 h prior to blood
      donation, (ii) plasma cotinine levels and (iii) chrysene/benzo[g,h,i]perylene
      ratios in the profile of personal PAH exposure. Furthermore, among the Halkida
      campus area subjects (but not the remaining subjects) positive correlations were
      observed between DNA adducts and (i) measured personal exposures to chrysene or
      benzo[a]pyrene, (ii) time of declared ETS exposure and (iii)
      chrysene/benzo[g,h,i] perylene ratios. These correlations suggest that, for a
      group suffering minimal exposure to urban air pollution, exposure to ETS was a
      significant determinant of the observed DNA damage. Gender had a consistent and
      significant effect on adduct levels (males having higher levels), which remained
      significant even after multiple regression analysis. Habitual consumption of
      roasted meat was significantly associated with an enhancement of adduct levels
      and the effect was strengthened when only individuals unexposed to ETS were taken
      into consideration. No significant effects were observed for other dietary
      parameters or factors reflecting exposure to air pollution.

PMID- 11532868
TI  - Age-related and tissue-specific accumulation of oxidative DNA base damage in 7,8
      dihydro-8-oxoguanine-DNA glycosylase (Ogg1) deficient mice.
AB  - Mutations that influence the repair of oxidative DNA modifications are expected
      to increase the steady-state (background) levels of these modifications and thus
      create a mutator phenotype that predisposes to malignant transformation. We have
      analysed the steady-state levels and repair kinetics of oxidative DNA
      modifications in cells of homozygous ogg1(-/-) null mice, which are deficient in
      Ogg1 protein, a DNA repair glycosylase that removes the miscoding base 8
      hydroxyguanine (8-oxoG) from the genome. Oxidative purine modifications including
      8-oxoG were quantified by means of an alkaline elution assay in combination with
      Fpg protein, the bacterial functional analogue of Ogg1 protein. In primary
      hepatocytes of adult ogg1(-/-) mice aged 9-12 months, the steady-state level of
      the lesions was 2.8-fold higher than in wild-type control mice. In contrast, no
      difference between ogg1(-/-) and wild-type mice was observed in splenocytes,
      spermatocytes and kidney cells. In hepatocytes of ogg1(-/-) mice, but not in wild
      type controls, the steady-state levels increased continuously over the whole
      lifespan. No significant accumulation of the oxidative base modifications was
      observed in ogg1(-/-) fibroblasts in culture when they were kept confluent for 8
      days. Both in confluent and proliferating ogg1(-/-) fibroblasts, the global
      repair of additional oxidative base modifications induced by photosensitization
      was 4-fold slower than in wild-type cells. The results suggest that the
      consequences of an Ogg1 defect are restricted to slowly proliferating tissues
      with high oxygen metabolism such as liver, because of a back-up mechanism for the
      repair of 8-oxoG residues that is independent of transcription and replication.

PMID- 11532869
TI  - Individual variation in the production of a 'bystander signal' following
      irradiation of primary cultures of normal human urothelium.
AB  - The existence of a bystander effect following both alpha and gamma irradiation of
      many cell lines is not now in dispute. The significance of this effect for cancer
      risk assessment and radiotherapy treatment planning requires demonstration of its
      relevance in vivo. The problem in demonstrating the existence of the effect in
      vivo is that other systemic effects may mask or confound the effect being
      investigated and it is practically impossible to attribute an effect in a
      particular cell to a signal produced in another irradiated cell. To approach this
      problem, we have developed an assay where fragments of human tissue can be
      irradiated ex vivo and the media harvested and added to unirradiated, allogenic
      explants or to a clonogenic cell line which has a well characterized and stable
      response to the bystander signal. The variation in production of the signal from
      patient to patient can thus be assessed using molecular and cellular endpoints. A
      study using tissue from over 100 patients and from mouse strains with well
      characterized responses to low level radiation exposure shows that there is
      variation in the effect of the signal produced by irradiated tissue from
      different patients. Gender, smoking status and the existence of a bladder
      malignancy influence the expression of the signal by normal urothelium. The
      effects of exposure to medium containing the signal are transmitted to distant
      progeny of the exposed cell population. The results may be important not only for
      understanding radiation risk mechanisms for protection but also for radiotherapy
      treatment planning where they may open new avenues for development of drugs for
      combined therapy.

PMID- 11532870
TI  - Stimulation of DNA synthesis and c-fos mRNA expression in primary rat hepatocytes
      by estrogens.
AB  - The mechanism(s) of tumour promotion in liver by estrogens is not well understood
      although growth stimulation is known to be one important element of their action.
      As a basis for studying mechanisms of growth control by estrogens, effects of
      both natural and synthetic estrogens on DNA synthesis and protooncogene c-fos
      mRNA expression were examined in primary cultures of normal rat hepatocytes.
      17beta-Estradiol (E(2)) alone was stimulatory and exhibited dramatic synergism
      with epidermal growth factor (EGF) in stimulating DNA synthesis. All estrogens
      tested (natural, synthetic, steroidal and non-steroidal) exhibited an ability to
      stimulate hepatocyte DNA synthesis. This appears to correlate with their ability
      to induce c-fos mRNA expression. In contrast to a non-estrogenic liver tumour
      promoter, phenobarbital, insulin is not permissive for the growth-stimulatory
      action of E(2). Dexamethasone, which is required for stimulation of DNA synthesis
      by the non-estrogenic tumour promoter alpha-hexachlorocyclohexane and
      tetradecanoylphorbol acetate, completely blocked E(2)-stimulated DNA synthesis.
      Such differential requirements for auxiliary factors suggests that estrogen and
      other non-estrogenic liver tumour promoters act via distinct mechanisms in
      stimulating hepatocyte DNA synthesis. E(2) alone had no effect, but when in
      combination with EGF significantly induced c-fos mRNA expression at early times
      in culture (maximal at 10 h in culture). Such findings, coupled with the
      observations that (i) E(2) and EGF were synergistic in growth stimulation, (ii)
      estrogen receptor levels are higher at early times in culture and (iii) the
      growth-stimulatory ability of E(2) is limited to 4-24 h in culture, support the
      notion that in hepatocytes E(2) acts via the estrogen receptor to transactivate c
      fos expression (an interaction with EGF), which ultimately culminates in enhanced
      DNA synthesis. Dexamethasone did not block E(2)-induced c-fos gene expression,
      suggesting that it acts in a pathway(s) distal to activation of fos gene
      expression. The possible inhibitory mechanisms of action of dexamethasone on E(2)
      stimulated DNA synthesis are discussed.

PMID- 11532871
TI  - Induction of cytochrome P450 enzymes and over-generation of oxygen radicals in
      beta-carotene supplemented rats.
AB  - Effects of beta-carotene (betaCT) on microsomal CYP-linked monooxygenases were
      investigated using both the regio- and stereo-selective hydroxylation of
      testosterone (as multibiomarker) and highly specific substrates as probes of
      various isoenzymes. CYP-catalyzed reactions were studied in the liver, kidney,
      lung and intestine of Sprague-Dawley rats of both sexes supplemented with 250 or
      500 mg/kg body wt betaCT (per os) in a single or repeated (daily for 5 days)
      fashion. Generalized boosting effects (2-15-fold increases) were observed in the
      various tissues for carcinogen metabolizing enzymes associated with CYP1A1/2,
      CYP3A1/2, CYP2E1, CYP2B1/2 and CYP2C11. Induction of the most affected CYPs was
      corroborated by western blot linked to densitometric analyses. Measurement of
      reactive oxygen species (ROS) produced by subcellular preparations from either
      control or betaCT supplemented rats was performed by EPR detection of the
      nitroxide radical yielded by the reaction with ROS of the hydroxylamine spin
      probe bis(1-hydroxy-2,2,6,6-tetramethyl-4-piperidinyl)decandioate. Marked ROS
      over-generation associated with CYP induction (up to 33-fold increase in the
      liver) was recorded in the various organs (liver > lung > intestine > kidney).
      CYP and ROS induction are substantially in keeping with the concentration of
      betaCT accumulated in the various tissues, the liver being the most affected
      organ. These findings are consistent with the concept that betaCT is a pro
      oxidant and potentially co-carcinogenic pro-vitamin, and may help explain why, in
      large quantities, it can have harmful effects in humans.

PMID- 11532872
TI  - Characteristics of mutations in the p53 gene in oral squamous cell carcinoma
      associated with betel quid chewing and cigarette smoking in Taiwanese.
AB  - p53 mutations are etiologically associated with the development of oral squamous
      cell carcinomas (OSCCs) or are associated with exposure to specific carcinogens.
      In this study, we used PCR-single strand conformation polymorphism and DNA
      sequencing to analyze the conserved regions of the p53 gene (exons 5-9) in OSCC
      tumor specimens from 187 patients with varied histories of betel quid, tobacco
      and alcohol use. Ninety-one of the 187 OSCCs (48.66%) showed p53 gene mutations
      at exons 5-9. The incidence of p53 mutations was not associated with age, sex,
      TNM stage, status of cigarette smoking or betel quid chewing. However, alcohol
      drinkers exhibited a significantly higher incidence (57/101, 56.44%) of p53
      mutations than non-users (39.53%, 34/86) (P = 0.02). The effect of alcohol on the
      incidence of p53 mutations was still statistically significant (RR = 2.24; 95%
      CI, 1.21-4.15) after adjustment for cigarette smoking and betel quid (BQ)
      chewing. G:C to A:T transitions were the predominant mutations observed and
      associated with BQ and tobacco use. Alcohol drinking could enhance these
      transitions. After adjustment for cigarette smoking and BQ chewing, alcohol
      drinking still showed an independent effect on G:C to A:T transitions (RR = 2.41;
      95% CI, 1.01-5.74). These findings strongly suggest an important contributive
      role of tobacco carcinogens to p53 mutation in this series of Taiwanese OSCCs and
      alcohol might enhance these mutagenic effects. As safrole-DNA adducts have been
      detected in 77% (23/30) of the OSCC tissues from Taiwanese oral cancer patients
      with a BQ chewing history, we cannot rule out the possibility that safrole or
      other carcinogens present in the BQ may cause a similar pattern of mutagenesis.
      Determination of the role of safrole and other carcinogens present in BQ on the
      pattern of p53 gene mutation in OSCC will require further study.

PMID- 11532873
TI  - The ability of four catechol estrogens of 17beta-estradiol and estrone to induce
      DNA adducts in Syrian hamster embryo fibroblasts.
AB  - Catechol estrogens are considered critical intermediates in estrogen-induced
      carcinogenesis. We demonstrated previously that 17beta-estradiol (E(2)), estrone
      (E(1)) and four of their catechol estrogens, 2- and 4-hydroxyestradiols (2- and 4
      OHE(2)), and 2- and 4-hydroxyestrones (2- and 4-OHE(1)) induce morphological
      transformation in Syrian hamster embryo (SHE) fibroblasts, and the transforming
      abilities vary as follows: 4-OHE(1) > 2-OHE(1) > 4-OHE(2) > 2-OHE(2) vertical
      line E(2), E(1). To examine the involvement of catechol estrogens in the
      initiation of hormonal carcinogenesis, we studied the ability of E(2), E(1) and
      their catechol estrogens to induce DNA adducts in SHE cells by using a (32)P-post
      labeling assay. DNA adducts were detected in cells treated with each of all the
      catechol estrogens at concentrations of 10 microg/ml for 1 h and more. 2- or 4
      OHE(2) formed a single DNA adduct, which was chromatographically distinct from
      each other. In contrast, 2- or 4-OHE(1) produced one major and one minor adduct,
      and the two adducts formed by each catechol estrogen exhibited identical
      mobilities on the chromatograms. Neither E(2) nor E(1) at concentrations up to 30
      microg/ml induced DNA adducts. The abilities of the estrogens to induce DNA
      adducts were ranked as follows: 4-OHE(1) > 2-OHE(1) > 4-OHE(2) > 2-OHE(2) > >
      E(2), E(1), which corresponds well to the transforming and carcinogenic abilities
      of the estrogens. In addition, the level of DNA adducts induced by the catechol
      estrogens was markedly decreased by co-treatment of cells with the antioxidant L
      ascorbic acid. The results indicate the possible involvement of oxidative
      metabolites of catechol estrogens of E(2) and E(1) in the initiation of
      endogenous estrogen-induced carcinogenesis.

PMID- 11532874
TI  - Effect of chloroform on dichloroacetic acid and trichloroacetic acid-induced
      hypomethylation and expression of the c-myc gene and on their promotion of liver
      and kidney tumors in mice.
AB  - Chloroform, dichloroacetic acid (DCA) and trichloroacetic acid (TCA) are mouse
      liver carcinogens that are chlorine disinfection by-products found in drinking
      water. The effect of chloroform on DCA and TCA-induced hypomethylation and
      expression of the c-myc gene and on their promotion of liver and kidney tumors
      was determined. B6C3F1 mice were administered 0, 400, 800 and 1600 mg/l
      chloroform in drinking water and 500 mg/kg DCA or TCA-administered daily by
      gavage. DCA, TCA and to a lesser extent chloroform decreased the methylation and
      increased the mRNA expression of the c-myc gene. Co-administering chloroform
      prevented only DCA and not TCA-induced hypomethylation and increased mRNA
      expression of the gene. The effect of chloroform on tumor promotion by DCA and
      TCA was determined in female and male B6C3F1 mice initiated on day 15 of age with
      N-methyl-N-nitrosourea. Starting at 5 weeks of age, the mice received in their
      drinking water DCA (3.2 g/l) or TCA (4.0 g/l) with 0, 800 or 1600 mg/l chloroform
      until they were killed at 36 weeks. Liver tumors promoted by DCA and TCA were
      predominantly basophilic except for DCA-treated female mice that were
      eosinophilic. Only DCA promoted foci of altered hepatocytes and they were
      eosinophilic in both sexes. Chloroform prevented DCA, but not TCA promotion of
      liver foci and tumors. In male mice, TCA promoted kidney tumors while DCA
      promoted kidney tumors only when co-administered with chloroform. Hence,
      chloroform prevented the hypomethylation and increased mRNA expression of the c
      myc gene and the promotion of liver tumors by DCA, while enhancing DCA-promotion
      of kidney tumors. Thus, the concurrent exposure to two carcinogens, chloroform
      and DCA resulted in less than additive activity in one organ and synergism in
      another organ.

PMID- 11532876
TI  - Areca nut extract and arecoline induced the cell cycle arrest but not apoptosis
      of cultured oral KB epithelial cells: association of glutathione, reactive oxygen
      species and mitochondrial membrane potential.
AB  - There are 600 million betel quid (BQ) chewers in the world. BQ chewing is a major
      etiologic factor of oral cancer. Areca nut (AN) and arecoline may inhibit the
      growth of oral mucosal fibroblasts (OMF) and keratinocytes. In this study, AN
      extract (100-800 microg/ml) and arecoline (20-120 microM) inhibited the growth of
      oral KB cells by 36-90 and 15-75%, respectively. Exposure to arecoline (> 0.2 mM)
      for 24 h induced G(2)/M cell cycle arrest of OMF and KB cells. Areca nut extract
      (> 400 microg/ml) also induced G(2)/M arrest of KB cells, being preceded by S
      phase arrest at 7-h of exposure. No evident sub-G(0)/G(1) peak was noted. Marked
      retraction and intracellular vacuoles formation of OMF and KB cells were
      observed. Glutathione (GSH) level, mitochondrial membrane potential (Deltabetam)
      and H(2)O(2) production of KB cells were measured by flow cytometry. GSH level
      [indicated by 5-chloromethyl-fluorescein (CMF) fluorescence] was depleted by 24-h
      exposure of KB cells to arecoline (0.4-1.2 mM) and AN extract (800-1200
      microg/ml), with increasing the percentage of cells in low CMF fluorescence. By
      contrast, arecoline (0.1-1.2 mM) and AN extract (800-1200 microg/ml) induced
      decreasing and increasing H(2)O(2) production (by 2',7'-dichloro- fluorescein
      fluorescence), respectively. Hyperpolarization of Deltabetam (increasing of
      rhodamine uptake) was noted by 24-h exposure of KB cells to arecoline (0.4-1.2
      mM) and AN extract (800-1200 microg/ml). AN extract (100- 1200 microg/ml) and
      arecoline (0.1-1.2 mM) induced little DNA fragmentation on KB cells within 24 h.
      These results indicate that AN ingredients are crucial in the pathogenesis of
      oral submucous fibrosis (OSF) and oral cancer by differentially inducing the
      dysregulation of cell cycle control, Deltabetam, GSH level and intracellular
      H(2)O(2) production, these events being not coupled with cellular apoptosis.

PMID- 11532875
TI  - Quantitation of androgen receptor gene expression in sporadic breast tumors by
      real-time RT-PCR: evidence that MYC is an AR-regulated gene.
AB  - Little is known of the function and clinical significance of the androgen
      receptor (AR) in human breast cancer. Paradoxically, synthetic progestins, such
      as medroxyprogesterone acetate, are used for second line hormone therapy of
      breast cancer following tamoxifen failure. A sensitive and accurate assay for AR
      expression in breast tumors is thus required. Here we have developed and
      validated a real-time RT-PCR assay to quantify AR gene expression at the mRNA
      level in a series of 131 patients with unilateral invasive primary breast tumors.
      AR expression varied widely in tumor tissues (by at least 3 orders of magnitude),
      being underexpressed in 24/131 (18.3%) and overexpressed in 45/131 (34.4%)
      relative to normal breast tissues. We observed links (or trends) between AR
      status and age, menopausal status, Scarff-Bloom-Richardson histopathological
      grade, lymph node status and estrogen receptor alpha and progesterone receptor
      status. High AR mRNA levels were negatively linked to MYC gene overexpression (P
      = 8 x 10(-6)), confirming previous in vitro studies. Our results also suggest a
      role of the ARA70 gene (which encodes a major AR co-activator) in the AR pathway
      dysregulation observed in breast cancer. This simple, rapid and semi-automated
      method will be useful for screening cancer patients for altered AR expression and
      for predicting the response to androgen therapy in AR-related cancer patients.

PMID- 11532877
TI  - Disruption of gap junctional intercellular communication by lindane is associated
      with aberrant localization of connexin43 and zonula occludens-1 in 42GPA9 Sertoli
      cells.
AB  - Lindane (gamma-hexachlorocyclohexane) is a lipid-soluble pesticide that exerts
      carcinogenic and reprotoxic properties. The mechanisms by which lindane alters
      testicular function are unclear. Sertoli cells control germ cell proliferation
      and differentiation through cell-cell communication, including gap junction
      intercellular communication. Using the 42GPA9 Sertoli cell line, we show that
      lindane, at a non-cytotoxic dose (50 microM), abolished gap junction
      intercellular communication (GJIC) between adjacent cells. This change was
      associated with a time-related diminution and redistribution of Cx43 from the
      membrane to the cytoplasmic perinuclear region. A similar alteration was observed
      for ZO-1, a tight junction component associated with Cx43, but not for occludin,
      an integral tight junction protein. After a 24 h lindane exposure, Cx43 and ZO-1
      colocalized within the cytoplasm and no modification of non-phosphorylated and
      phosphorylated isoforms of Cx43 was observed. By double immunofluorescent
      labelling we demonstrate that the cytoplasmic Cx43 signal was not present in
      either the endoplasmic reticulum/Golgi apparatus or lysosomes. These results
      suggest that lindane inhibits GJIC between Sertoli cells and that aberrant
      Cx43/ZO-1 localization may be responsible for this effect. The alterations in gap
      junctions induced by lindane in 42GPA9 Sertoli cells are similar to those
      observed in tumour cells and may be involved in the pathogenesis of neoplastic
      seminomal proliferation.

PMID- 11532878
TI  - Role of PKC and MAP kinase in EGF- and TPA-induced connexin43 phosphorylation and
      inhibition of gap junction intercellular communication in rat liver epithelial
      cells.
AB  - Gap junction intercellular communication (GJIC) is involved in the regulation of
      many cellular processes. The gap junction channels are made up of connexins and
      the flow of polar low molecular weight molecules through these channels is
      inhibited by several groups of substances, such as tumour promoters and growth
      factors. The phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA), chlordane
      and the growth factor epidermal growth factor (EGF) are potent inhibitors of GJIC
      in several cell types, including the rat liver epithelial cell line IAR6.1. The
      induced inhibition of communication by TPA and EGF in IAR6.1 cells is associated
      with hyperphosphorylation of connexin43, the connexin responsible for GJIC. Two
      enzyme inhibitors, PD98059, a specific inhibitor of MEK kinase, and GF109203X, a
      selective inhibitor of protein kinase C (PKC), were used to study the signalling
      pathways involved in the effect of EGF and TPA on GJIC, with the following
      conclusions. The inhibition of cell communication in IAR6.1 cells by EGF is
      likely to be mediated by direct phosphorylation of connexin43 by MAP kinase. TPA
      blocks GJIC mainly by the direct action of PKC, but also partly through cross
      talk with the MAP kinase pathway. Connexin43 hyperphosphorylation induced by TPA
      is, as for EGF, mediated through MAP kinase, while PKC seems to block GJIC either
      through other substrates or induces a type of connexin43 phosphorylation that
      causes no significant electrophoresis mobility shift.

PMID- 11532879
TI  - High susceptibility of Scid mice to colon carcinogenesis induced by azoxymethane
      indicates a possible caretaker role for DNA-dependent protein kinase.
AB  - Severe combined immunodeficiency (Scid) mice have defects in V(D)J recombination
      and DNA double-strand breaks repair caused by an inherited genetic defect in the
      catalytic subunit of DNA-dependent protein kinase (DNA-PKcs). Scid mice are
      highly susceptible to development of T-cell lymphomas, and because of the nature
      of its association with DNA repair and recombination, DNA-PKcs is considered to
      belong to the caretaker class of tumor suppressor genes. In the present study,
      the susceptibility of Scid mice to colon carcinogenesis due to administration of
      azoxymethane (AOM) was investigated. Significantly higher susceptibility in terms
      of induction of both aberrant crypt foci (ACFs), putative pre-cancerous lesions
      of the colon and colon cancers was observed as compared with the isogenic strain,
      C.B-17 mice. The incidences of colon tumors, either adenomas or adenocarcinomas,
      in Scid and C.B-17 mice after administration of AOM (10 mg/kg body weight/week)
      for 6 weeks were 87% (26 of 30) and 50% (15 of 30), respectively, by experimental
      week 22 (P < 0.01). The multiplicity of colon tumors in Scid mice was also
      significantly higher than in C.B-17 mice, being 2.2 +/- 1.5 and 0.9 +/- 1.2,
      respectively (P < 0.001). The present study clearly demonstrated high
      susceptibility of Scid mice to colon carcinogenesis, which might be attributable
      to disruption of the caretaker role of DNA-PK in colonic epithelial cells.

PMID- 11532881
TI  - Prediction of rodent carcinogenicity of aromatic amines: a quantitative structure
      activity relationships model.
AB  - The aromatic amines are widely used industrial chemicals and can be found in
      tobacco smoke as well as in products generated during cooking. In a previous
      study, we established quantitative structure-activity relationship (QSAR) models
      linking the carcinogenic potency of non-heterocyclic carcinogenic aromatic amines
      to a series of molecular determinants. We also found that QSAR models for
      carcinogenic potency were inadequate in describing the difference between
      carcinogenic and non-carcinogenic amines [Benigni,R., Giuliani,A., Franke,R. and
      Gruska,A. (2000) CHEM: Rev., 100, 3697-3714]. In this paper, we derived specific
      QSAR models for separating active from inactive amines. It appeared that
      hydrophobicity (as measured by the octanol/water partition coefficient, logP)
      played a major role in modulating the potency of the carcinogens, whereas mainly
      electronic (reactivity) and steric characteristics separated the carcinogens from
      the non-carcinogens. Interestingly, a similar pattern was previously demonstrated
      by us regarding their mutagenic activity [Benigni,R., Passerini,L., Gallo,G.,
      Giorgi,F. and Cotta-Ramusino,M. (1998) ENVIRON: Mol. Mutagen., 32, 75-83]. Based
      on the QSAR models found, the molecular determinants of the mechanisms of action
      of aromatic amines are discussed in detail. The QSAR models obtained can be used
      directly for estimating the carcinogenicity of other non-heterocyclic aromatic
      amines for which experimental data are not available. With the QSARs in Benigni
      et al. (2000) and the present results, a two-step prediction of carcinogenicity
      of aromatic amines is possible: (i) step 1, yes/no activity from the discriminant
      functions; and (ii) step 2, if the answer from step 1 is yes then prediction of
      the degree of potency from the equations in Benigni et al. (2000). Thus, QSAR
      models can contribute to the following: the direct synthesis of safer chemicals;
      the estimation of the risk posed by amines present in the environment; setting
      priorities for further experimentation, thus also reducing the use of
      experimental animals. Whereas the quality of in vivo experimental data is often
      questioned, the robustness and interpretability of the present results strongly
      support the reliability of the rodent carcinogenicity assay.

PMID- 11532880
TI  - Cyclooxygenase-2, malondialdehyde and pyrimidopurinone adducts of deoxyguanosine
      in human colon cells.
AB  - Cyclooxygenases (COX) catalyse the oxygenation of arachidonic acid to
      prostaglandin (PG) endoperoxides. Activity of one of the COX isoforms, COX-2,
      results in production of prostaglandin E(2) (PGE(2)) via the endoperoxide PGH(2).
      COX-2 has been implicated in the pathogenesis of colorectal cancer.
      Malondialdehyde (MDA) is a mutagen produced by spontaneous and enzymatic
      breakdown of PGH(2). MDA reacts with DNA to form adducts, predominantly the
      pyrimidopurinone adduct of deoxyguanosine (M(1)G). Here the hypothesis was tested
      that COX-2 activity in human colon cells results in formation of MDA and
      generation of M(1)G adducts. M(1)G was detected in basal cultures of human non
      malignant colon epithelial (HCEC) and malignant SW48, SW480, HT29 and HCA-7 colon
      cells, at levels from 77 to 148 adducts/10(8) nucleotides. Only HCA-7 and HT29
      cells expressed COX-2 protein. Levels of M(1)G correlated significantly (r =
      0.98, P < 0.001) with those of intracellular MDA determined colorimetrically in
      the four malignant cell types, but neither parameter correlated with expression
      of COX-2 or PG biosynthesis. Induction of COX-2 expression by phorbol 12
      myristate 13-acetate in HCEC cells increased PGE(2) production 20-fold and MDA
      concentration 3-fold. Selective inhibition of COX-2 activity in HCA-7 cells by NS
      398 significantly inhibited PGE(2) production, but altered neither MDA nor M(1)G
      levels. Malondialdehyde treatment of HCEC cells resulted in a doubling of M(1)G
      levels. These results show for the first time in human colon cells that COX-2
      activity is associated with formation of the endogenous mutagen, MDA. Moreover,
      they demonstrate the correlation between MDA concentration and M(1)G adduct
      levels in malignant cells.

PMID- 11532882
TI  - Catechol estrogen metabolites and conjugates in mammary tumors and hyperplastic
      tissue from estrogen receptor-alpha knock-out (ERKO)/Wnt-1 mice: implications for
      initiation of mammary tumors.
AB  - A novel model of breast cancer was established by crossing mice carrying the Wnt
      1 transgene (100% of adult females develop spontaneous mammary tumors) with the
      ERKO mouse line, in which mammary tumors develop despite a lack of functional
      estrogen receptor-alpha. To begin investigating whether metabolite-mediated
      genotoxicity of estrogens may play an important role in the initiation of mammary
      tumors, the pattern of estrogen metabolites and conjugates was examined in
      ERKO/Wnt-1 mice. Extracts of hyperplastic mammary tissue and mammary tumors were
      analyzed by HPLC with identification and quantification of compounds by
      multichannel electrochemical detection. Picomole amounts of the 4-catechol
      estrogens (CE) were detected, but their methoxy conjugates, as well as the 2-CE
      and their methoxy conjugates, were not. 4-CE conjugates with glutathione or its
      hydrolytic products (cysteine and N-acetylcysteine) were detected in picomole
      amounts in both tumors and hyperplastic mammary tissue, demonstrating the
      formation of CE-3,4-quinones. These preliminary findings show that the estrogen
      metabolite profile in the mammary tissue is unbalanced, in that the normally
      minor 4-CE metabolites were detected in the mammary tissue and not the normally
      predominant 2-CE. These results are consistent with the hypothesis that the
      mammary tumor development is primarily initiated by metabolism of estrogens to 4
      CE and, then, to CE-3,4-quinones, which may react with DNA to induce oncogenic
      mutations.

PMID- 11532884
TI  - Inhibitory synapse cover on the somata of excitatory neurons in macaque monkey
      visual cortex.
AB  - Electron microscopy was used in macaque monkey cortical area V1 to investigate
      what factors might determine the proportion of somatic membrane covered by
      inhibitory type 2 synapses. In a sample of 4654 excitatory neurons, synapse cover
      did not correlate consistently with cell variety (pyramid or spiny stellate),
      soma size, synaptic apposition length or thalamic input. There were significant
      differences in somatic synapse cover per layer, but the pattern of differences in
      cover among layers differed significantly between animals, suggesting that
      laminar environment alone is not a generally applicable determinant of amount of
      inhibitory synapse cover. The pattern of cover for cells in different layers was,
      however, similar between the two hemispheres of an individual monkey. Measures of
      inhibitory synapse cover on four sets of pyramidal neurons in layers 5 and 6,
      each with different efferent projection targets, showed that the sets differed
      significantly from other cells in their respective layers, and differed
      significantly from each other. These findings demonstrate that there is unique
      circuitry for different subsystems within single layers of cortex and provide a
      rationale for the rich variety of cortical GABAergic interneurons within single
      layers.

PMID- 11532885
TI  - Neural correlates of dual task interference can be dissociated from those of
      divided attention: an fMRI study.
AB  - When people perform two tasks simultaneously, the tasks are often executed slower
      and with more errors than when they are carried out as single tasks. This is
      called dual task interference. With functional magnetic resonance imaging (fMRI),
      we show that concurrently performed visual and somatosensory reaction time (RT)
      tasks engage almost identical volumes of cortical and subcortical motor
      structures. Moreover, dual RT tasks engaged additional cortical regions that are
      not activated by the component RT tasks had they been performed as single tasks.
      When the inter-stimulus interval was <300 ms, the first task interfered with the
      second, and a field in the right inferior frontal gyrus (RIFG) appeared with
      activity correlated with the increased RT to the second stimulus. This activation
      was spatially distinct from the cortical activity of the main effect of dual task
      performance. Thus, the performance of single RT tasks, dual RT tasks and dual RT
      tasks that interfere differ psychophysically and in the brain structures
      subserving these tasks. A short occupancy of the common motor structures can
      explain the interference effect. The increased activity of the RIFG correlated
      with the interference effect is very likely to be a specific outcome of
      situations where two concurrent tasks interfere with each other. The brain
      appears to recruit the RIFG for a subsequent (delayed) response when there is
      interference between dual tasks.

PMID- 11532886
TI  - Rapid regulation of GAD67 mRNA and protein level in cortical neurons after
      sensory learning.
AB  - Cortical representations of different modalities can be modified by sensory
      learning. Our previous studies in the barrel cortex showed that expansion of the
      cortical representation of a row of vibrissae could be induced by pairing
      stimulation of a row of vibrissae with a tail shock. The plastic change in
      cortical reactivity to the input used during the training was accompanied by
      increased density of GABA immunoreactive neurons in the involved row of cortical
      barrels. Using the same paradigm, the present study examined the pathway of GABA
      synthesis-expression of GAD67 mRNA and immunoreactivity of GAD67 isoenzyme in the
      barrel cortex of mice after sensory learning. In situ hybridization revealed that
      the GAD67 mRNA level was elevated in one row of barrels in the trained group as
      well as in controls receiving vibrissae stimulation alone. In contrast, elevation
      of immunoreactivity of the GAD67 protein occurred only in the trained group. The
      density of GABA-immunoreactive neurons in the hollows of barrels representing the
      row of vibrissae activated during the training was increased by 50%. These data
      indicated that sensory stimulation alone affected expression of the 67 kDa
      glutamate decarboxylase isoenzyme synthesis pathway, whereas the processes
      involved in cortical plasticity induced by associative learning modified this
      pathway additionally at the level of translation.

PMID- 11532887
TI  - Quantitative genetic modeling of variation in human brain morphology.
AB  - The degree to which individual variation in brain structure in humans is
      genetically or environmentally determined is as yet not well understood. We
      studied the brains of 54 monozygotic (33 male, 21 female) and 58 dizygotic (17
      male, 20 female, 21 opposite sex) pairs of twins and 34 of their full siblings
      (19 male, 15 female) by means of high resolution magnetic resonance imaging
      scans. Structural equation modeling was used to quantify the genetic and
      environmental contributions to phenotypic (co)variance in whole brain, gray and
      white matter volume of the cerebrum, lateral ventricle volume and associated
      variables such as intracranial volume and height. Because the cerebral cortex
      makes up more that two-thirds of the brain mass and almost three-quarters of its
      synapses, our data predominantly concerns the telencephalon. Genetic factors
      accounted for most of the individual differences in whole brain (90%), gray (82%)
      and white (88%) matter volume. Individual differences in lateral ventricle volume
      were best explained by a model containing common (58%) and unique (42%)
      environmental factors, indicating genes to be of no or minor influence. In our
      sample, genetic or environmental influences were not different for males and
      females. The same genes influenced brain volumes and intracranial volume and
      almost completely explained their high phenotypic correlation. Genes influencing
      gray and white matter overlapped to a large extent and completely determined
      their phenotypic correlation. The high heritability estimates that were found
      indicate that brain volumes may be useful as intermediate phenotypes in
      behavioral genetic research.

PMID- 11532888
TI  - Anterior cingulate cortex and response conflict: effects of frequency, inhibition
      and errors.
AB  - Anterior cingulate cortex (ACC) may play a key role in cognitive control by
      monitoring for the occurrence of response conflict (i.e. simultaneous activation
      of incompatible response tendencies). Low-frequency responding might provide a
      minimal condition for eliciting such conflict, as a result of the need to
      overcome a prepotent response tendency. We predicted that ACC would be
      selectively engaged during low-frequency responding, irrespective of the specific
      task situation. To test this hypothesis, we examined ACC activity during the
      performance of simple choice-discrimination tasks, using rapid event-related
      functional magnetic resonance imaging. Subjects were scanned while performing
      three tasks thought to tap different cognitive processes: 'Go/No-go' (response
      inhibition), 'oddball' (target detection), and two-alternative forced- choice
      (response selection). Separate conditions manipulated the frequency of relevant
      task events. Consistent with our hypothesis, the same ACC region was equally
      responsive to low-frequency events across all three tasks, but did not show
      differential responding when events occurred with equal frequency. Subregions of
      the ACC were also identified that showed heightened activity during the response
      inhibition condition, and on trials in which errors were committed. Task
      sensitive activity was also found in right prefrontal and parietal cortex
      (response inhibition), left superior temporal and tempoparietal cortex (target
      detection), and supplementary motor area (response selection). Taken together,
      the results are consistent with the hypothesis that the ACC serves as a generic
      detector of processing conflict arising when low-frequency responses must be
      executed, but also leave open the possibility that further functional
      specialization may occur within ACC subregions.

PMID- 11532889
TI  - Anterior cingulate cortex and response conflict: effects of response modality and
      processing domain.
AB  - Studies of a variety of higher cognitive functions consistently activate a region
      of anterior cingulate cortex (ACC), situated posterior to the genu and superior
      to the corpus callosum. However, it is not clear whether the same ACC region is
      activated for all response modalities (e.g. vocal and manual) and/or all
      processing domains (e.g. verbal and spatial). To explore this question, we used
      rapid event-related functional magnetic resonance imaging and a spatial Stroop
      task with conditions tapping both verbal and spatial processing. We also employed
      novel methods that allowed us to acquire the accuracy and reaction times of both
      manual and vocal responses. We found one large ACC region that demonstrated
      significant response conflict effects with both vocal and manual responses, and
      three ACC regions that demonstrated significant response conflict effects with
      both spatial and verbal processing. We did not find any ACC regions that
      demonstrated activity selective to either a specific response modality or
      processing domain. Thus, our results suggest that the same regions of ACC are
      responsive to conflict arising with both manual and vocal output and with both
      spatial and verbal processing.

PMID- 11532890
TI  - Area 3a: topographic organization and cortical connections in marmoset monkeys.
AB  - The functional organization of area 3a, a cortical field proposed to be involved
      in somato-motor-vestibular integration, has never been described for any primate.
      In the present investigation, the topographic organization and connections of
      area 3a were examined in marmosets using electrophysiological recording and
      anatomical tracing techniques. Multi-unit neuronal activity was recorded at a
      number of closely spaced sites; receptive fields (RFs) for neurons were
      determined, and the optimal stimulus was identified. In all cases, neurons in
      area 3a responded to the stimulation of deep receptors on the contralateral body.
      The representation of the body in area 3a was from the toes and foot, to the
      hindlimb, trunk, forelimb, hand and face in a mediolateral progression. In all
      cases electrophysiological results were related to myeloarchitecture, and the map
      in area 3a was found to be coextensive with a strip of lightly to moderately
      myelinated cortex just rostral to the darkly myelinated 3b. To examine the
      cortical connections of area 3a, injections of anatomical tracers were made into
      electrophysiologically identified body part representations. Area 3a has dense
      intrinsic connections and receives substantial inputs from the primary motor
      cortex (M1), the supplementary motor area (SMA), areas 1 and 2, the second
      somatosensory area (S2), and areas in posterior parietal cortex (PP). The
      connections of area 3a indicate that integration of cortical representations of
      body parts occurs both within area 3a and between area 3a and other somatosensory
      and motor areas. In addition, there are differential patterns of interconnections
      between behaviorally relevant body part representations of area 3a, such as the
      forelimb, compared to other body part representations (hindlimb/ trunk),
      especially with 'higher order' cortical fields. This suggests that 3a may be an
      important component in a network that generates a common frame of reference for
      hand and eye coordinated reaching tasks.

PMID- 11532891
TI  - Structural asymmetries in the human brain: a voxel-based statistical analysis of
      142 MRI scans.
AB  - The use of computational approaches in the analysis of high resolution magnetic
      resonance images (MRI) of the human brain provides a powerful tool for in vivo
      studies of brain anatomy. Here, we report results obtained with a voxel-wise
      statistical analysis of hemispheric asymmetries in regional 'amounts' of gray
      matter, based on MRI scans obtained in 142 healthy young adults. Firstly, the
      voxel-wise analysis detected the well-known frontal (right > left) and occipital
      (left > right) petalias. Secondly, our analysis confirmed the presence of left
      greater-than-right asymmetries in several posterior language areas, including the
      planum temporale and the angular gyrus; no significant asymmetry was detected in
      the anterior language regions. We also found previously described asymmetries in
      the cingulate sulcus (right > left) and the caudate nucleus (right > left).
      Finally, in some brain regions we observed highly significant asymmetries that
      were not reported before, such as in the anterior insular cortex (right > left).
      The above asymmetries were observed in men and women. Our results thus provide
      confirmation of the known structural asymmetries in the human brain as well as
      new findings that may stimulate further research of hemispheric specialization.

PMID- 11532892
TI  - An endogenous adrenoceptor ligand potentiates excitatory synaptic transmission in
      cultured hippocampal neurons.
AB  - Noradrenergic inputs modulate hippocampal function via distinct receptors. In
      hippocampal neuronal cultures, mRNA expression of adrenoceptor subtypes is
      maintained from 1 day in vitro (DIV) to 22 DIV. Noradrenaline dose-dependently
      stimulates phosphoinositide (PI) breakdown in both immature and mature cultures
      through the activation of alpha1 receptors. At 22 DIV, basal PI breakdown depends
      on excitatory synaptic activity since it is decreased by tetrodotoxin or
      glutamate receptor antagonists. At 22 DIV, a similar decrease of basal PI
      breakdown is also observed with alpha1, alpha2 or beta adrenoceptor antagonists.
      These effects are not additive with that produced by tetrodotoxin. Adrenergic
      antagonists also strongly reduce spontaneous excitatory post-synaptic currents
      (sEPSC) as evidenced by whole cell recording. Therefore, in hippocampal cultures,
      excitatory transmission is modulated by a tonic activation of adrenoceptors
      probably produced by an endogenous ligand. Indeed, (i) the depletion of
      catecholamine pools by reserpine also decreases both basal PI metabolism and
      sEPSC; (ii) hippocampal neurons possess both tyrosine hydroxylase (TH) and
      dopamine-beta-hydroxylase mRNAs, encoding enzymes required for catecholamine
      synthesis; and (iii) some hippocampal neurons show TH-immunoreactivity. TH
      positive cells are also detected in E18 hippocampal sections. Thus, cultured
      hippocampal neurons synthesize and release an adrenergic-like ligand, which
      tonically potentiates excitatory synaptic transmission in mature cultures.

PMID- 11532893
TI  - Krieg Cortical Kudos 2001. The Cortical Explorer Award: Zoltan Nusser.

PMID- 11532895
TI  - When is cAMP not cAMP? Effects of compartmentalization.

PMID- 11532896
TI  - Cytokine receptor CX3CR-1 and fractalkine: new factors in the atherosclerosis
      drama?

PMID- 11532897
TI  - Taking the gender gap to heart.

PMID- 11532898
TI  - Transcriptional regulation of vascular development.
AB  - Vascular development is a highly organized sequence of events that requires the
      correct spatial and temporal expression of specific sets of genes leading to the
      development of a primary vascular network. The first step in this process is the
      differentiation of pluripotent stem cells into endothelial cells. This is
      followed by endothelial proliferation, migration, and eventual formation of
      endothelial tubes. Maturation of these primitive tubes into fully developed blood
      vessels requires the recruitment of surrounding pericytes and their
      differentiation into vascular smooth muscle cells. Many of the events that occur
      during vasculogenesis are recapitulated during angiogenesis. Transcription
      factors have been shown to serve as master switches for regulating a number of
      developmental processes. Using a candidate gene approach, the genomic regulatory
      regions required to direct vascular-specific gene expression of several receptor
      tyrosine kinases that are critical for vasculogenesis have been characterized and
      some of the transcription factors that are involved in the regulation of these
      genes have recently been identified. Many of these factors are also involved in
      the regulation of hematopoiesis and may have overlapping functions in determining
      hematopoietic and endothelial differentiation. Targeted disruption of other
      transcription factors that were not previously thought to be involved in vascular
      development have also been recently shown to play a role in blood vessel
      development. The purpose of this review is to provide an update on the progress
      that has been made in our understanding of the transcriptional regulation of
      vascular development over the past few years.

PMID- 11532899
TI  - Assessment of risks associated with cardiovascular gene therapy in human
      subjects.
AB  - Clinical trials of cardiovascular gene therapy, whether using viral (53%) or
      nonviral (47%) vectors, have thus far disclosed no evidence indicative of
      inflammatory or other complications, including death, directly attributable to
      the vector used. Indeed, despite the fact that initial trials of cardiovascular
      gene therapy targeted patients with end-stage vascular disease, including
      critical limb ischemia and refractory myocardial ischemia, the mortality for
      patients enrolled in clinical trials of cardiovascular gene therapy reported to
      date compares favorably with mortality for similar groups of patients in
      contemporary controlled studies of medical or interventional therapies. The most
      common morbidity reported after cardiovascular gene transfer is lower extremity
      edema; in contrast to data involving genetically engineered mice, however,
      evidence of life- or limb-threatening edema has not been described in any
      patients, including patients after gene transfer for myocardial ischemia.
      Concerns regarding the potential for angiogenic cytokines to promote the
      progression of atherosclerosis are not supported by angiographic follow-up of
      patients with coronary or peripheral vascular disease. The levels and duration of
      gene expression investigated for therapeutic angiogenesis transfer have been
      unassociated with hemangioma formation. Likewise, there is little evidence from
      either preclinical or clinical studies to support the notion that the
      administration of angiogenic growth factors, per se, is sufficient to stimulate
      the growth of neoplasms. Patients enrolled in clinical studies of angiogenic
      cytokines, including patients with diabetes and a previous history of
      retinopathy, have disclosed no evidence to suggest that ocular pathology is a
      risk of angiogenic growth factor gene transfer.

PMID- 11532900
TI  - Association between polymorphism in the chemokine receptor CX3CR1 and coronary
      vascular endothelial dysfunction and atherosclerosis.
AB  - Fractalkine, a chemokine expressed by inflamed endothelium, induces leukocyte
      adhesion and migration via the receptor CX3CR1, and the CX3CR1 polymorphism V249I
      affects receptor expression and function. Here we show that this polymorphism is
      an independent risk factor for atherosclerotic coronary artery disease (CAD).
      Genotyping of the CX3CR1-V249I polymorphism was performed in a cohort of 339
      white individuals who underwent cardiac catheterization (n=197 with and n=142
      without CAD, respectively). In 203 patients, intracoronary acetylcholine 15
      microg/min) and sodium nitroprusside (20 microg/min) were administered to test
      endothelium-dependent and -independent coronary vascular function, respectively.
      Change in coronary vascular resistance (DeltaCVR) was measured as an index of
      microvascular dilation. An association was observed between presence of the
      CX3CR1 I249 allele and reduced prevalence of CAD, independent of established CAD
      risk factors (odds ratio=0.54 [95% confidence interval, 0.30 to 0.96], P=0.03).
      Angiographic severity of CAD was also lower in these subjects (P=0.01).
      Furthermore, endothelium-dependent vasodilation was greater in these individuals
      compared with individuals homozygous for the CX3CR1-V249 allele (DeltaCVR during
      acetylcholine = -46+/-3% versus -36+/-3%, respectively, P=0.02), whereas DeltaCVR
      with sodium nitroprusside was similar in both groups (-55+/-2% versus -53+/-2%,
      P=0.45). The association between CX3CR1 genotype and endothelial function was
      independent of established risk factors and presence of CAD by multivariate
      analysis (P=0.02). Thus, the CX3CR1 I249 allele is associated with decreased risk
      of CAD and improved endothelium-dependent vasodilation. This suggests that CX3CR1
      may be involved in the pathogenesis of CAD.

PMID- 11532901
TI  - Novel competitive inhibitor of NAD(P)H oxidase assembly attenuates vascular O(2)(
      ) and systolic blood pressure in mice.
AB  - We previously reported enhanced expression of the p67(phox) and gp91(phox)
      components of NAD(P)H oxidase in angiotensin (Ang) II-induced hypertension,
      suggesting de novo assembly in response to Ang II. To examine the direct
      involvement of NAD(P)H oxidases in Ang II-induced O(2)(-) production, we designed
      a chimeric peptide that inhibits p47(phox) association with gp91(phox) in NAD(P)H
      oxidase (gp91ds-tat). This was achieved by linking a 9-amino acid peptide (aa)
      derived from HIV-coat protein (tat) to a 9-aa sequence of gp91(phox) (known to
      interact with p47(phox)). As a control, we constructed a chimera containing tat
      and a scrambled gp91 sequence (scramb-tat). We found that gp91ds-tat decreased
      O(2)(-) levels in aortic rings treated with Ang II (10 pmol/L) but had no effect
      on either the O(2)(-)-generating enzyme xanthine oxidase or potassium superoxide
      generated O(2)(-). We infused vehicle, Ang II (0.75 mg. kg(-1). d(-1)), Ang
      II+gp91ds-tat (10 mg. kg(-1). d(-1)), or Ang II+scramb-tat intraperitoneally in
      C57Bl/6 mice and measured systolic blood pressure (SBP) on days 0, 3, 5, and 7 of
      infusion. SBP increased by day 3 in mice given Ang II and Ang II+scramb-tat but
      was significantly lower with Ang II+gp91-tat. On day 7, SBP was still
      significantly inhibited in mice given Ang II+gp91ds-tat, whereas Ang II-induced
      O(2)(-) production was inhibited throughout the aorta as detected by
      dihydroethidium staining, consistent with the ability of this inhibitor to block
      the various vascular NAD(P)H oxidase isoforms. These data support the hypothesis
      that inhibition of the interaction of p47(phox) and gp91(phox) (or its
      homologues) can block O(2)(-) production and attenuate blood pressure elevation
      in mice.

PMID- 11532902
TI  - Antiinflammatory and antiarteriosclerotic actions of HMG-CoA reductase inhibitors
      in a rat model of chronic inhibition of nitric oxide synthesis.
AB  - Recent studies suggest that some of the beneficial effects of 3-hydroxyl-3
      methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) may be due to
      their cholesterol-lowering independent effects on the blood vessels. Chronic
      inhibition of endothelial nitric oxide (NO) synthesis by oral administration of
      N(omega)-nitro-L-arginine methyl ester (L-NAME) to rats induces early vascular
      inflammation as well as subsequent arteriosclerosis. The aim of the study is to
      test whether treatment with statins attenuates such arteriosclerotic changes
      through their cholesterol-lowering independent effects. We investigated the
      effect of statins (pravastatin and cerivastatin) on the arteriosclerotic changes
      in the rat model. We found that treatment with statins did not affect serum lipid
      levels but markedly inhibited the L-NAME-induced vascular inflammation and
      arteriosclerosis. Treatment with statins augmented endothelial NO synthase
      activity in L-NAME-treated rats. We also found the L-NAME induced increase in Rho
      membrane translocation in hearts and its prevention by statins. Such
      vasculoprotective effects of statins were suppressed by the higher dose of L
      NAME. In summary, in this study, we found that statins such as pravastatin and
      cerivastatin inhibited vascular inflammation and arteriosclerosis through their
      lipid-lowering independent actions in this model. Such antiarteriosclerotic
      effects may involve the increase in endothelial NO synthase activity and the
      inhibition of Rho activity.

PMID- 11532903
TI  - Transgenic expression of sarcoplasmic reticulum Ca(2+) atpase modifies the
      transition from hypertrophy to early heart failure.
AB  - To examine the contribution of sarcoplasmic reticulum Ca(2+) ATPase (SERCA2a) to
      early heart failure, we subjected transgenic (TG) mice expressing SERCA2a gene
      and wild-type (WT) mice to aortic stenosis (AS) for 7 weeks. At an early stage of
      hypertrophy (4-week AS), in vivo hemodynamic and echocardiographic indices were
      similar in TG and WT mice. By 7 weeks of AS, which is the stage of early failure
      in this model, TG mice with AS had lower mortality than WT mice with AS (6.7%
      versus 29%). The magnitude of left ventricular (LV) hypertrophy was similar in WT
      and TG 7-week AS mice. In vivo LV systolic function was higher in TG than in WT 7
      week AS mice. In LV myocytes loaded with fluo-3, fractional cell shortening and
      the amplitude of the [Ca(2+)](i) transients were higher in TG than in WT 7-week
      AS mice under baseline conditions (0.5 Hz, 1.5 mmol/L [Ca(2+)](o), 25 degrees C).
      The rates of relengthening and decay in [Ca(2+)](i) were faster in TG than in WT
      7-week AS myocytes. In myocytes from WT 7-week AS compared with sham-operated WT
      mice, contractile reserve in response to rapid pacing was depressed with impaired
      augmentation of both peak-systolic [Ca(2+)](i) and the SR Ca(2+) load. In
      contrast, contractile reserve and the capacity to augment SR Ca(2+) load were
      maintained in TG 7-week AS mice. SERCA2a protein levels were depressed in WT 7
      week AS mice, but were preserved in TG 7-week AS mice. These data suggest that
      defective SR Ca(2+) loading contributes to the onset of contractile failure in
      animals with chronic pressure overload.

PMID- 11532904
TI  - O(2) modulates large-conductance Ca(2+)-dependent K(+) channels of rat
      chemoreceptor cells by a membrane-restricted and CO-sensitive mechanism.
AB  - Hypoxic inhibition of large-conductance Ca(2+)-dependent K(+) channels (maxiK) of
      rat carotid body type I cells is a well-established fact. However, the molecular
      mechanisms of such inhibition and the role of these channels in the process of
      hypoxic transduction remain unclear. We have examined the mechanisms of
      interaction of O(2) with maxiK channels exploring the effect of hypoxia on maxiK
      currents recorded with the whole-cell and the inside-out configuration of the
      patch-clamp technique. Hypoxia inhibits channel activity both in whole-cell and
      in excised membrane patches. This effect is strongly voltage- and Ca(2+)
      dependent, being maximal at low [Ca(2+)] and low membrane potential. The analysis
      of single-channel kinetics reveals a gating scheme comprising three open and five
      closed states. Hypoxia inhibits channel activity increasing the time the channel
      spends in the longest closed states, an effect that could be explained by a
      decrease in the Ca(2+) sensitivity of those closed states. Reducing maxiK
      channels with dithiothreitol (DTT) increases channel open probability, whereas
      oxidizing the channels with 2,2'-dithiopyridine (DTDP) has the opposite effect.
      These results suggest that hypoxic inhibition is not related with a reduction of
      channel thiol groups. However, CO, a competitive inhibitor of O(2) binding to
      hemoproteins, fully reverts hypoxic inhibition, both at the whole-cell and the
      single-channel level. We conclude that O(2) interaction with maxiK channels does
      not require cytoplasmic mediators. Such interaction could be mediated by a
      membrane hemoprotein that, as an O(2) sensor, would modulate channel activity.

PMID- 11532905
TI  - Gender-based differences in cardiac repolarization in mouse ventricle.
AB  - The mouse heart has become a widely used model for genetic studies of heart
      diseases. Thus, understanding gender differences in mouse cardiac repolarization
      is crucial to the interpretation of such studies. The objective of this study was
      to evaluate whether there are gender differences in cardiac repolarization in
      mouse ventricle and to gain insights into the ionic and molecular mechanisms
      underlying these differences. Action potential durations (APDs) and K(+) currents
      in male and female ventricular myocytes were compared using a patch-clamp
      technique. APD(20), APD(50), and APD(90) were found to be significantly longer in
      females than males. Examination of the different K(+) currents revealed that a
      significantly lower current density exists in female ventricular myocytes
      compared with male myocytes for the ultrarapid delayed rectifier K(+) current,
      I(Kur) (at +30 mV, male, 33.2+/-2.9 pA/pF [n= 22]; female, 20.9+/-1.73 pA/pF [n=
      19], P<0.001). Consistent with these findings were the results of the
      ribonuclease protection assay, Western blots, and confocal analysis that showed a
      significantly lower expression level of Kv1.5 (coding for I(Kur)) in female
      compared with male ventricle. The additional K(+) currents present in mouse
      ventricle exhibited no gender differences. In agreement with these
      electrophysiological data, no differences in the expression levels for the K(+)
      channels underlying these currents were detected between both sexes. This study
      demonstrates that adult mice exhibit gender differences in cardiac
      repolarization. The expression of Kv1.5 and of its corresponding K(+) current,
      I(Kur), is significantly lower in female mouse ventricle, and as a result, the
      APD is lengthened.

PMID- 11532906
TI  - Glucagon-like peptide-1 increases cAMP but fails to augment contraction in adult
      rat cardiac myocytes.
AB  - The gut hormone, glucagon-like peptide-1 (GLP-1), which is secreted in nanomolar
      amounts in response to nutrients in the intestinal lumen, exerts cAMP/protein
      kinase A-mediated insulinotropic actions in target endocrine tissues, but its
      actions in heart cells are unknown. GLP-1 (10 nmol/L) increased intracellular
      cAMP (from 5.7+/-0.5 to 13.1+/-0.12 pmol/mg protein) in rat cardiac myocytes. The
      effects of cAMP-doubling concentrations of both GLP-1 and isoproterenol (ISO, 10
      nmol/L) on contraction amplitude, intracellular Ca(2+) transient (CaT), and pH(i)
      in indo-1 and seminaphthorhodafluor (SNARF)-1 loaded myocytes were compared.
      Whereas ISO caused a characteristic increase (above baseline) in contraction
      amplitude (160+/-34%) and CaT (70+/-5%), GLP-1 induced a significant decrease in
      contraction amplitude (-27+/-5%) with no change in the CaT after 20 minutes.
      Neither pertussis toxin treatment nor exposure to the cGMP-stimulated
      phosphodiesterase (PDE2) inhibitor erythro-9-(2-hydroxy-3-nonyl)adenine or the
      nonselective PDE inhibitor 3-isobutyl-1-methylxanthine nor the phosphatase
      inhibitors okadaic acid or calyculin A unmasked an ISO-mimicking response of GLP
      1. In SNARF-1-loaded myocytes, however, both ISO and GLP-1 caused an
      intracellular acidosis (DeltapH(i) -0.09+/-0.02 and -0.08+/-0.03, respectively).
      The specific GLP-1 antagonist exendin 9-39 and the cAMP inhibitory analog Rp-8CPT
      cAMPS inhibited both the GLP-1-induced intracellular acidosis and the negative
      contractile effect. We conclude that in contrast to beta-adrenergic signaling,
      GLP-1 increases cAMP but fails to augment contraction, suggesting the existence
      of functionally distinct adenylyl cyclase/cAMP/protein kinase A compartments,
      possibly determined by unique receptor signaling microdomains that are not
      controlled by pertussis toxin-sensitive G proteins or by enhanced local PDE or
      phosphatase activation. Furthermore, GLP-1 elicits a cAMP-dependent modest
      negative inotropic effect produced by a decrease in myofilament-Ca(2+)
      responsiveness probably resulting from intracellular acidification.

PMID- 11532907
TI  - Reactive oxygen species mediate amplitude-dependent hypertrophic and apoptotic
      responses to mechanical stretch in cardiac myocytes.
AB  - Oxidative stress stimulates both growth and apoptosis in cardiac myocytes in
      vitro. We investigated whether oxidative stress mediates hypertrophy and
      apoptosis in cyclically stretched ventricular myocytes. Neonatal rat ventricular
      myocytes cultured on laminin-coated silastic membranes were stretched cyclically
      (1 Hz) at low (nominal 5%) and high (nominal 25%) amplitudes for 24 hours.
      Stretch caused a graded increase in superoxide anion production as assessed by
      superoxide dismutase (SOD)-inhibitable cytochrome c reduction or electron
      paramagnetic resonance spectroscopy. The role of reactive oxygen species (ROS)
      was assessed using the cell-permeable SOD/catalase mimetics Mn(II/III)tetrakis(1
      methyl-4-peridyl) (MnTMPyP) and EUK-8. Stretch-induced increases in protein
      synthesis ((3)H-leucine incorporation) and cellular protein content were
      completely inhibited by MnTMPyP (0.05 mmol/L) at both low and high amplitudes of
      stretch. In contrast, while MnTMPyP inhibited basal atrial natriuretic factor
      (ANF) mRNA expression, the stretch-induced increase in ANF mRNA expression was
      not inhibited by MnTMPyP. In contrast to hypertrophy, only high-amplitude stretch
      increased myocyte apoptosis, as reflected by increased DNA fragmentation on gel
      electrophoresis and an approximately 3-fold increase in the number of TUNEL
      positive myocytes. Similarly, only high-amplitude stretch increased the
      expression of bax mRNA. Myocyte apoptosis and bax expression stimulated by high
      amplitude stretch were inhibited by MnTMPyP. Both low- and high-amplitude stretch
      caused rapid phosphorylation of ERK1/2, while high-, but not low-, amplitude
      stretch caused phosphorylation of JNKs. Activation of both ERK1/2 and JNKs was
      ROS-dependent. Thus, cyclic strain causes an amplitude-related increase in ROS,
      associated with differential activation of kinases and induction of hypertrophic
      and apoptotic phenotypes.

PMID- 11532908
TI  - Phosphorylation of mitochondrial elongation factor Tu in ischemic myocardium:
      basis for chloramphenicol-mediated cardioprotection.
AB  - The objective of this study was to identify the mitochondrial proteins that
      undergo changes in phosphorylation during global ischemia and reperfusion in the
      isolated rabbit heart. We also assessed whether the cardioprotective intervention
      of ischemic preconditioning affected mitochondrial protein phosphorylation. We
      established a reconstituted system using isolated mitochondria and cytosol from
      control or ischemic hearts. We found that phosphorylation of a 46-kDa protein on
      a serine residue was increased in ischemia and that phosphorylation was reduced
      in control or preconditioned hearts. Using 2D gel electrophoresis and mass
      spectrometry, we have identified the 46-kDa protein as mitochondrial
      translational elongation factor Tu (EF-Tu(mt)). These data reveal that ischemia
      and preconditioning modulate the phosphorylation of EF-Tu(mt) and suggest that
      the mitochondrial protein synthesis machinery may be regulated by
      phosphorylation. Phosphorylation of mitochondrial EF-Tu has not been previously
      described; however, in prokaryotes, EF-Tu phosphorylation inhibits protein
      translation. We hypothesized that phosphorylation of mitochondrial EF-Tu would
      inhibit mitochondrial protein translation and attempted to reproduce the effect
      with inhibition of mitochondrial protein synthesis by chloramphenicol. We found
      that chloramphenicol pretreatment significantly reduced infarct size, suggesting
      that mitochondrial protein synthesis is one determinant of myocardial injury
      during ischemia and reperfusion.

PMID- 11532909
TI  - The Iroquois family of genes: from body building to neural patterning.
AB  - The Iroquois (Iro) family of genes are found in nematodes, insects and
      vertebrates. They usually occur in one or two genomic clusters of three genes
      each and encode transcriptional controllers that possess a characteristic
      homeodomain. The Iro genes function early in development to specify the identity
      of diverse territories of the body, such as the dorsal head and dorsal mesothorax
      of Drosophila and the neural plate of Xenopus. In some aspects they act in the
      same way as classical selector genes, but they display specific properties that
      place them into a category of their own. Later in development in both Drosophila
      and vertebrates, the Iro genes function again to subdivide those territories into
      smaller domains.

PMID- 11532910
TI  - EGL-38 Pax regulates the ovo-related gene lin-48 during Caenorhabditis elegans
      organ development.
AB  - The Pax gene egl-38 plays an important role in the development of several organs
      in C. elegans. To understand how a Pax transcription factor influences distinct
      developmental choices in different cells and tissue types, we have characterized
      a second gene, lin-48. lin-48 functions with egl-38 in the development of one
      structure, the hindgut, but not in other tissues such as the egg-laying system.
      We show that lin-48 encodes a C2H2 zinc-finger protein that is similar to the
      product of the Drosophila gene ovo and is expressed in the hindgut cells that
      develop abnormally in lin-48 mutants. We present evidence that lin-48 is a target
      for EGL-38 in hindgut cells. We show that lin-48 requires egl-38 for its
      expression in the hindgut. Using deletion analysis, we have identified two
      elements in the lin-48 promoter that are necessary for lin-48 expression. We
      demonstrate that EGL-38 binds with high affinity to one of these elements. In
      addition, we have observed genetic interactions between mutations in the lin-48
      promoter and specific alleles of egl-38. These experiments demonstrate a
      functional link between Pax and Ovo transcription factors, and provide a model
      for how Pax transcription factors can regulate different target genes in
      different cells.

PMID- 11532912
TI  - barren inflorescence2 regulates axillary meristem development in the maize
      inflorescence.
AB  - Organogenesis in plants is controlled by meristems. Shoot apical meristems form
      at the apex of the plant and produce leaf primordia on their flanks. Axillary
      meristems, which form in the axils of leaf primordia, give rise to branches and
      flowers and therefore play a critical role in plant architecture and
      reproduction. To understand how axillary meristems are initiated and maintained,
      we characterized the barren inflorescence2 mutant, which affects axillary
      meristems in the maize inflorescence. Scanning electron microscopy, histology and
      RNA in situ hybridization using knotted1 as a marker for meristematic tissue show
      that barren inflorescence2 mutants make fewer branches owing to a defect in
      branch meristem initiation. The construction of the double mutant between barren
      inflorescence2 and tasselsheath reveals that the function of barren
      inflorescence2 is specific to the formation of branch meristems rather than bract
      leaf primordia. Normal maize inflorescences sequentially produce three types of
      axillary meristem: branch meristem, spikelet meristem and floral meristem.
      Introgression of the barren inflorescence2 mutant into genetic backgrounds in
      which the phenotype was weaker illustrates additional roles of barren
      inflorescence2 in these axillary meristems. Branch, spikelet and floral meristems
      that form in these lines are defective, resulting in the production of fewer
      floral structures. Because the defects involve the number of organs produced at
      each stage of development, we conclude that barren inflorescence2 is required for
      maintenance of all types of axillary meristem in the inflorescence. This defect
      allows us to infer the sequence of events that takes place during maize
      inflorescence development. Furthermore, the defect in branch meristem formation
      provides insight into the role of knotted1 and barren inflorescence2 in axillary
      meristem initiation.

PMID- 11532911
TI  - ELT-5 and ELT-6 are required continuously to regulate epidermal seam cell
      differentiation and cell fusion in C. elegans.
AB  - The C. elegans epidermis is a simple epithelium comprised of three major cell
      types, the seam, syncytial and P cells. While specification of all major
      epidermal cells is known to require the ELT-1 GATA transcription factor, little
      is known about how the individual epidermal cell types are specified. We report
      that elt-5 and -6, adjacent genes encoding GATA factors, are essential for the
      development of the lateral epidermal cells, the seam cells. Inhibition of elt-5
      and -6 function by RNA-mediated interference results in penetrant late embryonic
      and early larval lethality. Seam cells in affected animals do not differentiate
      properly: the alae, seam-specific cuticular structures, are generally absent and
      expression of several seam-specific markers is blocked. In addition, elt-3, which
      encodes another GATA factor normally expressed in non-seam epidermis, is often
      ectopically expressed in the seam cells of affected animals, demonstrating that
      ELT-5 and -6 repress elt-3 expression in wild-type seam cells. Seam cells in
      affected animals often undergo inappropriate fusion with the epidermal syncytia.
      Interference of elt-5 and -6 function during larval development can cause fusion
      of all seam cells with the surrounding syncytia and pronounced defects in
      molting. elt-5 and -6 are both expressed in seam cells and many other cells, and
      are apparently functionally interchangeable. Their expression is controlled by
      separable tissue-specific regulatory elements and the apportionment of
      monocistronic versus dicistronic transcription of both genes appears to be
      subject to cell-type-specific regulation. Collectively, these findings indicate
      that elt-5 and -6 function continuously throughout C. elegans development to
      regulate seam cell differentiation and cell fusion.

PMID- 11532913
TI  - Gene expression profiles in Ciona intestinalis tailbud embryos.
AB  - A set of 3423 expressed sequence tags derived from the Ciona intestinalis tailbud
      embryos was categorized into 1213 independent clusters. When compared with DNA
      Data Bank of Japan database, 502 clusters of them showed significant matches to
      reported proteins with distinct function, whereas 184 lacked sufficient
      information to be categorized (including reported proteins with undefined
      function) and 527 had no significant similarities to known proteins. Sequence
      similarity analyses of the 502 clusters in relation to the biosynthetic function,
      as well as the structure of the message population at this stage, demonstrated
      that 390 of them were associated with functions that many kinds of cells use, 85
      with cell-cell communication and 27 with transcription factors and other gene
      regulatory proteins. All of the 1213 clusters were subjected to whole-mount in
      situ hybridization to analyze the gene expression profiles at this stage. A total
      of 387 clusters showed expression specific to a certain tissue or organ; 149
      showed epidermis-specific expression; 34 were specific to the nervous system; 29
      to endoderm; 112 to mesenchyme; 32 to notochord; and 31 to muscle. Many genes
      were also specifically expressed in multiple tissues. The study also highlighted
      characteristic gene expression profiles dependent on the tissues. In addition,
      several genes showed intriguing expression patterns that have not been reported
      previously; for example, four genes were expressed specifically in the nerve cord
      cells and one gene was expressed only in the posterior part of muscle cells. This
      study provides molecular markers for each of the tissues and/or organs that
      constitutes the Ciona tailbud embryo. The sequence information will also be used
      for further genome scientific approach to explore molecular mechanisms involved
      in the formation of one of the most primitive chordate body plans.

PMID- 11532914
TI  - Investigation of leading edge formation at the interface of amnioserosa and
      dorsal ectoderm in the Drosophila embryo.
AB  - The leading edge (LE) is a single row of cells in the Drosophila embryonic
      epidermis that marks the boundary between two fields of cells: the amnioserosa
      and the dorsal ectoderm. LE cells play a crucial role in the morphogenetic
      process of dorsal closure and eventually form the dorsal midline of the embryo.
      Mutations that block LE differentiation result in a failure of dorsal closure and
      embryonic lethality. How LE cells are specified remains unclear. To explore
      whether LE cells are specified in response to early dorsoventral patterning
      information or whether they arise secondarily, we have altered the extent of
      amnioserosa and dorsal ectoderm genetically, and assayed LE cell fate. We did not
      observe an expansion of LE fate in dorsalized or ventralized mutants.
      Furthermore, we observed that the LE fate arises as a single row of cells,
      wherever amnioserosa tissue and dorsal epidermis are physically juxtaposed. Taken
      together our data indicate that LE formation is a secondary consequence of early
      zygotic dorsal patterning signals. In particular, proper LE specification
      requires the function of genes such as u-shaped and hindsight, which are direct
      transcriptional targets of the early Decapentaplegic/Screw patterning gradient,
      to establish a competency zone from which LE arises. We propose that subsequent
      inductive signaling between amnioserosa and dorsal ectoderm restricts the
      formation of LE to a single row of cells.

PMID- 11532915
TI  - Interactions between Wnt and Vg1 signalling pathways initiate primitive streak
      formation in the chick embryo.
AB  - The posterior marginal zone (PMZ) of the chick embryo has Nieuwkoop centre-like
      properties: when transplanted to another part of the marginal zone, it induces a
      complete embryonic axis, without making a cellular contribution to the induced
      structures. However, when the PMZ is removed, the embryo can initiate axis
      formation from another part of the remaining marginal zone. Chick Vg1 can mimic
      the axis-inducing ability of the PMZ, but only when misexpressed somewhere within
      the marginal zone. We have investigated the properties that define the marginal
      zone as a distinct region. We show that the competence of the marginal zone to
      initiate ectopic primitive streak formation in response to cVg1 is dependent on
      Wnt activity. First, within the Wnt family, only Wnt8C is expressed in the
      marginal zone, in a gradient decreasing from posterior to anterior. Second,
      misexpression of Wnt1 in the area pellucida enables this region to form a
      primitive streak in response to cVg1. Third, the Wnt antagonists Crescent and Dkk
      1 block the primitive streak-inducing ability of cVg1 in the marginal zone. These
      findings suggest that Wnt activity defines the marginal zone and allows cVg1 to
      induce an axis. We also present data suggesting some additional complexity:
      first, the Vg1 and Wnt pathways appear to regulate the expression of downstream
      components of each other's pathway; and second, misexpression of different Wnt
      antagonists suggests that different classes of Wnts may cooperate with each other
      to regulate axis formation in the normal embryo.

PMID- 11532916
TI  - Prx1 and Prx2 are upstream regulators of sonic hedgehog and control cell
      proliferation during mandibular arch morphogenesis.
AB  - The aristaless-related homeobox genes Prx1 and Prx2 are required for correct
      skeletogenesis in many structures. Mice that lack both Prx1 and Prx2 functions
      display reduction or absence of skeletal elements in the skull, face, limbs and
      vertebral column. A striking phenotype is found in the lower jaw, which shows
      loss of midline structures, and the presence of a single, medially located
      incisor. We investigated development of the mandibular arch of Prx1(-/-)Prx2(-/-)
      mutants to obtain insight into the molecular basis of the lower jaw
      abnormalities. We observed in mutant embryos a local decrease in proliferation of
      mandibular arch mesenchyme in a medial area. Interestingly, in the oral
      epithelium adjacent to this mesenchyme, sonic hedgehog (Shh) expression was
      strongly reduced, indicative of a function for Prx genes in indirect regulation
      of SHH: Wild-type embryos that were exposed to the hedgehog-pathway inhibitor,
      jervine, partially phenocopied the lower jaw defects of Prx1(-/-)Prx2(-/-)
      mutants. In addition, this treatment led to loss of the mandibular incisors. We
      present a model that describes how loss of Shh expression in Prx1(-/-)Prx2(-/-)
      mutants leads to abnormal morphogenesis of the mandibular arch.

PMID- 11532917
TI  - Timing of endogenous activin-like signals and regional specification of the
      Xenopus embryo.
AB  - Signaling by activin-like ligands is important for induction and patterning of
      mesoderm and endoderm. We have used an antibody that specifically recognizes the
      phosphorylated and activated form of Smad2, an intracellular transducer of
      activin-like ligands, to examine how this signaling pathway patterns the early
      mesendoderm. In contrast to the simple expectation that activin-like signaling
      should be highest on the dorsal side of the gastrula stage embryo, we have found
      that while Smad2 phosphorylation is highest dorsally before gastrulation,
      signaling is attenuated dorsally and is highest on the ventral side by mid
      gastrulation. Early dorsal initiation of Smad2 phosphorylation results from
      cooperation between the vegetally localized maternal transcription factor VegT
      and dorsally localized beta-catenin. The subsequent ventral appearance of Smad2
      phosphorylation is dependent on VegT, but not on signaling from the dorsal side.
      Dorsal attenuation of Smad2 phosphorylation during gastrulation is mediated by
      early dorsal expression of feedback inhibitors of activin-like signals. In
      addition to regulation of Smad2 phosphorylation by the expression of activin-like
      ligands and their antagonists, the responsiveness of embryonic cells to activin
      like ligands is also temporally regulated. Ectopic Vg1, Xnr1 and derriere all
      fail to activate Smad2 phosphorylation until after the midblastula transition,
      and the onset of responsiveness to these ligands is independent of transcription.
      Furthermore, the timing of cellular responsiveness differs for Xnr1 and derriere,
      and these distinct temporal patterns of responsiveness can be correlated with
      their distinctive phenotypic effects. These observations suggest that the timing
      of endogenous activin-like signaling is a determinant of patterning in the early
      Xenopus embryo.

PMID- 11532918
TI  - Rho kinases play an obligatory role in vertebrate embryonic organogenesis.
AB  - Rho-associated kinases (Rho kinases), which are downstream effectors of RhoA
      GTPase, regulate diverse cellular functions including actin cytoskeletal
      organization. We have demonstrated that Rho kinases also direct the early stages
      of chick and mouse embryonic morphogenesis. We observed that Rho kinase
      transcripts were enriched in cardiac mesoderm, lateral plate mesoderm and the
      neural plate. Treatment of neurulating embryos with Y27632, a specific inhibitor
      of Rho kinases, blocked migration and fusion of the bilateral heart primordia,
      formation of the brain and neural tube, caudalward movement of Hensen's node, and
      establishment of normal left-right asymmetry. Moreover, Y27632 induced precocious
      expression of cardiac alpha-actin, an early marker of cardiomyocyte
      differentiation, coincident with the upregulated expression of serum response
      factor and GATA4. In addition, specific antisense oligonucleotides significantly
      diminished Rho kinase mRNA levels and replicated many of the teratologies induced
      by Y27632. Thus, our study reveals new biological functions for Rho kinases in
      regulating major morphogenetic events during early chick and mouse development.

PMID- 11532919
TI  - Separable and redundant regulatory determinants in Cactus mediate its dorsal
      group dependent degradation.
AB  - Dorsal-ventral polarity within the Drosophila syncytial blastoderm embryo is
      determined by the maternally encoded dorsal group signal transduction pathway
      that regulates nuclear localization of the transcription factor Dorsal. Nuclear
      uptake of Dorsal, a Rel/NFkappaB homolog, is controlled by the interaction with
      its cognate IkappaB inhibitor protein Cactus, which is degraded on the ventral
      side of the embryo in response to dorsal group signaling. Previous studies have
      suggested that an N-terminally located kinase target motif similar to that found
      in IkappaB proteins is involved in the spatially controlled degradation of
      Cactus. We report studies of the in vivo function and distribution of fusion
      proteins comprising segments of Cactus attached to Escherichia coli beta
      galactosidase (lacZ). Full-length Cactus-lacZ expressed in vivo normalizes the
      ventralized phenotype of embryos that lack Cactus and faithfully reconstitutes
      dorsal group-regulated degradation, while fusion protein constructs that lack the
      first 125 amino acids of Cactus escape dorsal group-dependent degradation.
      Furthermore, Cactus-lacZ constructs that lack only the putative IkappaB-dependent
      kinase target-like motif can nevertheless undergo spatially regulated dorsal
      group-dependent degradation and we have identified the regulatory determinant
      responsible for dorsal group-dependent degradation of Cactus in the absence of
      this motif. Taken together, our studies indicate the presence of two distinct
      redundantly acting determinants in the N terminus of Cactus that direct dorsal
      group-dependent degradation. Strikingly, the regulatory domain of human
      IkappaBalpha can also direct polarized degradation of Cactus-lacZ fusion protein.

PMID- 11532920
TI  - Goosecoid promotes head organizer activity by direct repression of Xwnt8 in
      Spemann's organizer.
AB  - Formation of the vertebrate body plan is controlled by discrete head and trunk
      organizers that establish the anteroposterior pattern of the body axis. The
      Goosecoid (Gsc) homeodomain protein is expressed in all vertebrate organizers and
      has been implicated in the activity of Spemann's organizer in Xenopus. The role
      of Gsc in organizer function was examined by fusing defined transcriptional
      regulatory domains to the Gsc homeodomain. Like native Gsc, ventral injection of
      an Engrailed repressor fusion (Eng-Gsc) induced a partial axis, while a VP16
      activator fusion (VP16-Gsc) did not, indicating that Gsc functions as a
      transcriptional repressor in axis induction. Dorsal injection of VP16-Gsc
      resulted in loss of head structures anterior to the hindbrain, while axial
      structures were unaffected, suggesting a requirement for Gsc function in head
      formation. The anterior truncation caused by VP16-Gsc was fully rescued by Frzb,
      a secreted Wnt inhibitor, indicating that activation of ectopic Wnt signaling was
      responsible, at least in part, for the anterior defects. Supporting this idea,
      Xwnt8 expression was activated by VP16-Gsc in animal explants and the dorsal
      marginal zone, and repressed by Gsc in Activin-treated animal explants and the
      ventral marginal zone. Furthermore, expression of Gsc throughout the marginal
      zone inhibited trunk formation, identical to the effects of Frzb and other Xwnt8
      inhibitors. A region of the Xwnt8 promoter containing four consensus homeodomain
      binding sites was identified and this region mediated repression by Gsc and
      activation by VP16-Gsc, consistent with direct transcriptional regulation of
      Xwnt8 by Gsc. Therefore, Gsc promotes head organizer activity by direct
      repression of Xwnt8 in Spemann's organizer and this activity is essential for
      anterior development.

PMID- 11532921
TI  - Forebrain and midbrain development requires epiblast-restricted Otx2
      translational control mediated by its 3' UTR.
AB  - Otx genes play an important role in brain development. Previous mouse models
      suggested that the untranslated regions (UTRs) of Otx2 mRNA may contain
      regulatory element(s) required for its post-transcriptional control in epiblast
      and neuroectoderm. In order to study this, we have perturbed the 3' UTR of Otx2
      by inserting a small fragment of DNA from the lambda phage. Otx2(lambda) mutants
      exhibited proper gastrulation and normal patterning of the early anterior neural
      plate, but from 8.5 days post coitum they developed severe forebrain and midbrain
      abnormalities. OTX2 protein levels in Otx2(lambda) mutants were heavily reduced
      in the epiblast, axial mesendoderm and anterior neuroectoderm but not in the
      visceral endoderm. At the molecular level, we found out that the ability of the
      Otx2(lambda) mRNA to form efficient polyribosome complexes was impaired. Sequence
      analysis of the Otx2-3' UTR revealed a 140 bp long element that is present only
      in vertebrate Otx2 genes and conserved in identity by over 80%. Our data provide
      experimental evidence that murine brain development requires accurate
      translational control of Otx2 mRNA in epiblast and neuronal progenitor cells.
      This leads us to hypothesise that this control might have important evolutionary
      implications.

PMID- 11532922
TI  - ribbon encodes a novel BTB/POZ protein required for directed cell migration in
      Drosophila melanogaster.
AB  - During development, directed cell migration is crucial for achieving proper shape
      and function of organs. One well-studied example is the embryonic development of
      the larval tracheal system of Drosophila, in which at least four signaling
      pathways coordinate cell migration to form an elaborate branched network
      essential for oxygen delivery throughout the larva. FGF signaling is required for
      guided migration of all tracheal branches, whereas the DPP, EGF receptor, and
      Wingless/WNT signaling pathways each mediate the formation of specific subsets of
      branches. Here, we characterize ribbon, which encodes a BTB/POZ-containing
      protein required for specific tracheal branch migration. In ribbon mutant
      tracheae, the dorsal trunk fails to form, and ventral branches are stunted;
      however, directed migrations of the dorsal and visceral branches are largely
      unaffected. The dorsal trunk also fails to form when FGF or Wingless/WNT
      signaling is lost, and we show that ribbon functions downstream of, or parallel
      to, these pathways to promote anterior-posterior migration. Directed cell
      migration of the salivary gland and dorsal epidermis are also affected in ribbon
      mutants, suggesting that conserved mechanisms may be employed to orient cell
      migrations in multiple tissues during development.

PMID- 11532923
TI  - Synergy between Hoxa1 and Hoxb1: the relationship between arch patterning and the
      generation of cranial neural crest.
AB  - Hoxa1 and Hoxb1 have overlapping synergistic roles in patterning the hindbrain
      and cranial neural crest cells. The combination of an ectoderm-specific
      regulatory mutation in the Hoxb1 locus and the Hoxa1 mutant genetic background
      results in an ectoderm-specific double mutation, leaving the other germ layers
      impaired only in Hoxa1 function. This has allowed us to examine neural crest and
      arch patterning defects that originate exclusively from the neuroepithelium as a
      result of the simultaneous loss of Hoxa1 and Hoxb1 in this tissue. Using
      molecular and lineage analysis in this double mutant background we demonstrate
      that presumptive rhombomere 4, the major site of origin of the second pharyngeal
      arch neural crest, is reduced in size and has lost the ability to generate neural
      crest cells. Grafting experiments using wild-type cells in cultured normal or
      double mutant mouse embryos demonstrate that this is a cell-autonomous defect,
      suggesting that the formation or generation of cranial neural crest has been
      uncoupled from segmental identity in these mutants. Furthermore, we show that
      loss of the second arch neural crest population does not have any adverse
      consequences on early patterning of the second arch. Signalling molecules are
      expressed correctly and pharyngeal pouch and epibranchial placode formation are
      unaffected. There are no signs of excessive cell death or loss of proliferation
      in the epithelium of the second arch, suggesting that the neural crest cells are
      not the source of any indispensable mitogenic or survival signals. These results
      illustrate that Hox genes are not only necessary for proper axial specification
      of the neural crest but that they also play a vital role in the generation of
      this population itself. Furthermore, they demonstrate that early patterning of
      the separate components of the pharyngeal arches can proceed independently of
      neural crest cell migration.

PMID- 11532924
TI  - Hyaluronan-associated adhesive cues control fiber segregation in the hippocampus.
AB  - In various brain regions, particularly in the hippocampus, afferent fiber
      projections terminate in specific layers. Little is known about the molecular
      cues governing this laminar specificity. To this end we have recently shown that
      the innervation pattern of entorhinal fibers to the hippocampus is mimicked by
      the lamina-specific adhesion of entorhinal cells on living hippocampal slices,
      suggesting a role of adhesion molecules in the positioning of entorhinal fibers.
      Here, we have analyzed the role of extracellular matrix components in mediating
      this lamina-specific adhesion. We show that hyaluronidase treatment of
      hippocampal slices abolishes lamina-specific adhesion as well as layer-specific
      growth of entorhinal fibers to the dentate outer molecular layer in organotypic
      slice cultures. We conclude that hyaluronan-associated molecules play a crucial
      role in the formation of the lamina-specific entorhinal projection to the
      hippocampus.

PMID- 11532925
TI  - Retinal axon growth cones respond to EphB extracellular domains as inhibitory
      axon guidance cues.
AB  - Axon pathfinding relies on cellular signaling mediated by growth cone receptor
      proteins responding to ligands, or guidance cues, in the environment. Eph
      proteins are a family of receptor tyrosine kinases that govern axon pathway
      development, including retinal axon projections to CNS targets. Recent
      examination of EphB mutant mice, however, has shown that axon pathfinding within
      the retina to the optic disc is dependent on EphB receptors, but independent of
      their kinase activity. Here we show a function for EphB1, B2 and B3 receptor
      extracellular domains (ECDs) in inhibiting mouse retinal axons when presented
      either as substratum-bound proteins or as soluble proteins directly applied to
      growth cones via micropipettes. In substratum choice assays, retinal axons tended
      to avoid EphB-ECDs, while time-lapse microscopy showed that exposure to soluble
      EphB-ECD led to growth cone collapse or other inhibitory responses. These results
      demonstrate that, in addition to the conventional role of Eph proteins signaling
      as receptors, EphB receptor ECDs can also function in the opposite role as
      guidance cues to alter axon behavior. Furthermore, the data support a model in
      which dorsal retinal ganglion cell axons heading to the optic disc encounter a
      gradient of inhibitory EphB proteins which helps maintain tight axon
      fasciculation and prevents aberrant axon growth into ventral retina. In
      conclusion, development of neuronal connectivity may involve the combined
      activity of Eph proteins serving as guidance receptors and as axon guidance cues.

PMID- 11532926
TI  - Lysosomal cysteine proteases: facts and opportunities.
AB  - From their discovery in the first half of the 20th century, lysosomal cysteine
      proteases have come a long way: from being the enzymes non-selectively degrading
      proteins in lysosomes to being those responsible for a number of important
      cellular processes. Some of the features and roles of their structures,
      specificity, regulation and physiology are discussed.

PMID- 11532927
TI  - Hsp70 interactions with the p53 tumour suppressor protein.

PMID- 11532928
TI  - Activation of integrins in endothelial cells by fluid shear stress mediates Rho
      dependent cytoskeletal alignment.
AB  - Fluid shear stress is a critical determinant of vascular remodeling and
      atherogenesis. Both integrins and the small GTPase Rho are implicated in
      endothelial cell responses to shear but the mechanisms are poorly understood. We
      now show that shear stress rapidly stimulates conformational activation of
      integrin alpha(v)beta3 in bovine aortic endothelial cells, followed by an
      increase in its binding to extracellular cell matrix (ECM) proteins. The shear
      induced new integrin binding to ECM induces a transient inactivation of Rho
      similar to that seen when suspended cells are plated on ECM proteins. This
      transient inhibition is necessary for cytoskeletal alignment in the direction of
      flow. The results therefore define the role of integrins and Rho in a pathway
      leading to endothelial cell adaptation to flow.

PMID- 11532929
TI  - Expression of Cdc18/Cdc6 and Cdt1 during G2 phase induces initiation of DNA
      replication.
AB  - Cdc18/Cdc6 and Cdt1 are essential initiation factors for DNA replication. In this
      paper we show that expression of Cdc18 in fission yeast G2 cells is sufficient to
      override the controls that ensure one S phase per cell cycle. Cdc18 expression in
      G2 induces DNA synthesis by re-firing replication origins and recruiting the MCM
      Cdc21 to chromatin in the presence of low levels of Cdt1. However, when Cdt1 is
      expressed together with Cdc18 in G2, cells undergo very rapid, uncontrolled DNA
      synthesis, accumulating DNA contents of 64C or more. Our data suggest that Cdt1
      may potentiate re-replication by inducing origins to fire more persistently,
      possibly by stabilizing Cdc18 on chromatin. In addition, low level expression of
      a mutant form of Cdc18 that cannot be phosphorylated by cyclin-dependent kinases
      is not sufficient to induce replication in G2, but does so only when co-expressed
      with Cdt1. Thus, regulation of both Cdc18 and Cdt1 in G2 plays a crucial role in
      preventing the re-initiation of DNA synthesis until the next cell cycle.

PMID- 11532930
TI  - Folded HasA inhibits its own secretion through its ABC exporter.
AB  - Gram-negative bacterial proteins secreted by ABC exporters carry a secretion
      signal in their carboxylic extremities. This characteristic suggests that the
      polypeptide needs to be fully synthesized before it can be secreted and,
      therefore, presumably may fold at least in part before its secretion. We
      investigated the relationship between folding and secretion using HasA, a
      hemoprotein of Serratia marcescens secreted into the extracellular medium by a
      dedicated Has ABC exporter. We first demonstrated that when HasA is sequestered
      in the cytoplasm it can acquire its tertiary structure, as assessed from its
      capacity to bind heme. The cytoplasmic pool of HasA cannot be secreted and
      inhibits the secretion of newly synthesized molecules. HasA folding in the
      cytoplasm was independent of either its capacity to bind heme or the presence of
      SecB, although SecB is essential for HasA secretion. Our findings indicate a
      strong coupling between synthesis and secretion in the type I secretion pathway.

PMID- 11532931
TI  - Glide2, a second glial promoting factor in Drosophila melanogaster.
AB  - The fly glial cell deficient/glial cell missing (glide/gcm) gene codes for a
      transcription factor that induces gliogenesis. Lack of its product eliminates
      lateral glial cells in the embryonic nervous system. Here we identify a second
      gene, glide2, that is homologous to glide/gcm in the binding domain and that is
      also necessary and sufficient to promote glial differentiation. glide2 codes for
      a transcription factor that displays a weaker and delayed expression compared
      with glide/gcm. The two genes, which are located 27 kb apart and share cis
      regulatory elements, are able to auto- and cross-regulate, indicating that they
      form a gene complex. Finally, we show that lack of both products eliminates all
      lateral glial cells, which means that the two genes contain all the fly lateral
      glial promoting activity.

PMID- 11532932
TI  - RNA interference of a trypanosome topoisomerase II causes progressive loss of
      mitochondrial DNA.
AB  - We studied the function of a Trypanosoma brucei topoisomerase II using RNA
      interference (RNAi). Expression of a topoisomerase II double-stranded RNA as a
      stem-loop caused specific degradation of mRNA followed by loss of protein. After
      6 days of RNAi, the parasites' growth rate declined and the cells subsequently
      died. The most striking phenotype upon induction of RNAi was the loss of
      kinetoplast DNA (kDNA), the cell's catenated mitochondrial DNA network. The loss
      of kDNA was preceded by gradual shrinkage of the network and accumulation of
      gapped free minicircle replication intermediates. These facts, together with the
      localization of the enzyme in two antipodal sites flanking the kDNA, show that a
      function of this topoisomerase II is to attach free minicircles to the network
      periphery following their replication.

PMID- 11532933
TI  - Ski7p G protein interacts with the exosome and the Ski complex for 3'-to-5' mRNA
      decay in yeast.
AB  - Two cytoplasmic mRNA-decay pathways have been characterized in yeast, and both
      are initiated by shortening of the 3'-poly(A) tail. In the major 5'-to-3' decay
      pathway, the deadenylation triggers removal of the 5'-cap, exposing the
      transcript body for 5'-to-3' degradation. An alternative 3'-to-5' decay pathway
      also follows the deadenylation and requires two multi-complexes: the exosome
      containing various 3'-exonucleases and the Ski complex consisting of the RNA
      helicase Ski2p, Ski3p and Ski8p. In addition, Ski7p, which has an N-terminal
      domain and a C-terminal elongation factor 1alpha-like GTP-binding domain, is
      involved in the 3'-to-5' decay. However, physical interaction between the exosome
      and the Ski complex, together with the function of Ski7p, has remained unknown.
      Here we report that the N domain of Ski7p is required and sufficient for the 3'
      to-5' decay. Furthermore, the exosome and the Ski complex interact with the
      different regions of Ski7p N domain, and both interactions are required for the
      3'-to-5' decay. Thus, Ski7p G protein appears to function as a signal-coupling
      factor between the two multi-complexes operating in the 3'-to-5' mRNA-decay
      pathway.

PMID- 11532934
TI  - Roles for ligases in the RNA editing complex of Trypanosoma brucei: band IV is
      needed for U-deletion and RNA repair.
AB  - Trypanosome RNA editing utilizes a seven polypeptide complex that includes two
      RNA ligases, band IV and band V. We now find that band IV protein contributes to
      the structural stability of the editing complex, so its lethal genetic knock-out
      could reflect structural or catalytic requirements. To assess the catalytic role
      in editing, we generated cell lines which inducibly replaced band IV protein with
      an enzymatically inactive but structurally conserved version. This induction
      halts cell growth, showing that catalytic activity is essential. These induced
      cells have impaired in vivo editing, specifically of RNAs requiring uridylate (U)
      deletion; unligated RNAs cleaved at U-deletion sites accumulated. Additionally,
      mitochondrial extracts of cells with reduced band IV activity were deficient in
      catalyzing U-deletion, specifically at its ligation step, but were not deficient
      in U-insertion. Thus band IV ligase is needed to seal RNAs in U-deletion. U
      insertion does not appear to require band IV, so it might use the other ligase of
      the editing complex. Furthermore, band IV ligase was also found to serve an RNA
      repair function, both in vitro and in vivo.

PMID- 11532935
TI  - Mutation in Brca2 stimulates error-prone homology-directed repair of DNA double
      strand breaks occurring between repeated sequences.
AB  - Mutation of BRCA2 causes familial early onset breast and ovarian cancer. BRCA2
      has been suggested to be important for the maintenance of genome integrity and to
      have a role in DNA repair by homology- directed double-strand break (DSB) repair.
      By studying the repair of a specific induced chromosomal DSB we show that loss of
      Brca2 leads to a substantial increase in error-prone repair by homology-directed
      single-strand annealing and a reduction in DSB repair by conservative gene
      conversion. These data demonstrate that loss of Brca2 causes misrepair of
      chromosomal DSBs occurring between repeated sequences by stimulating use of an
      error-prone homologous recombination pathway. Furthermore, loss of Brca2 causes a
      large increase in genome-wide error-prone repair of both spontaneous DNA damage
      and mitomycin C-induced DNA cross-links at the expense of error-free repair by
      sister chromatid recombination. This provides insight into the mechanisms that
      induce genome instability in tumour cells lacking BRCA2.

PMID- 11532936
TI  - The tight interallelic positional coincidence that distinguishes T-cell receptor
      Jalpha usage does not result from homologous chromosomal pairing during
      ValphaJalpha rearrangement.
AB  - The T-cell receptor (TCR) alpha locus is thought to undergo multiple cycles of
      secondary rearrangements that maximize the generation of alphabeta T cells.
      Taking advantage of the nucleotide sequence of the human Valpha and Jalpha
      segments, we undertook a locus-wide analysis of TCRalpha gene rearrangements in
      human alphabeta T-cell clones. In most clones, ValphaJalpha rearrangements
      occurred on both homologous chromosomes and, remarkably, resulted in the use of
      two neighboring Jalpha segments. No such interallelic coincidence was found for
      the position of the two rearranged Valpha segments, and there was only a loose
      correlation between the 5' or 3' chromosomal position of the Valpha and Jalpha
      segments used in a given rearrangement. These observations question the
      occurrence of extensive rounds of secondary Valpha-->Jalpha rearrangements and of
      a coordinated and polarized usage of the Valpha and Jalpha libraries.
      Fluorescence in situ hybridization analysis of developing T cells in which
      TCRalpha rearrangements are taking place showed that the interallelic positional
      coincidence in Jalpha usage cannot be explained by the stable juxtaposition of
      homologous Jalpha clusters.

PMID- 11532937
TI  - Ara6, a plant-unique novel type Rab GTPase, functions in the endocytic pathway of
      Arabidopsis thaliana.
AB  - Ara6 of Arabidopsis thaliana is a novel member of the Rab/Ypt GTPase family with
      unique structural features. It resembles Rab5 GTPases best, but lacks a large
      part of the C-terminal hypervariable region and the cysteine motif, and instead
      harbors an extra stretch of amino acid residues containing myristoylation and
      palmitoylation sites at the N-terminus. Ara6 is tightly associated with membranes
      and is expressed constitutively. In contrast, the conventional Rab5 ortholog,
      Ara7, is highly expressed only in actively dividing cells. Examination of green
      fluorescent protein (GFP)-tagged proteins indicates that both Ara6 and Ara7 are
      distributed on a subpopulation of endosomes and suggests their roles in endosomal
      fusion. The endosomal localization of Ara6 requires N-terminal fatty acylation,
      nucleotide binding and the C-terminal amino acid sequence coordinately. Proteins
      similar to Ara6 are found only in higher plants and thus represent a novel class
      of Rab GTPases regulating endocytic function in a plant- specific manner.

PMID- 11532938
TI  - NRG1 represses yeast-hypha morphogenesis and hypha-specific gene expression in
      Candida albicans.
AB  - We have characterized CaNrg1 from Candida albicans, the major fungal pathogen in
      humans. CaNrg1 contains a zinc finger domain that is conserved in transcriptional
      regulators from fungi to humans. It is most closely related to ScNrg1, which
      represses transcription in a Tup1-dependent fashion in Saccharomyces cerevisiae.
      Inactivation of CaNrg1 in C.albicans causes filamentous and invasive growth,
      derepresses hypha-specific genes, increases sensitivity to some stresses and
      attenuates virulence. A tup1 mutant displays similar phenotypes. However, unlike
      tup1 cells, nrg1 cells can form normal hyphae, generate chlamydospores at normal
      rates and grow at 42 degrees C. Transcript profiling of 2002 C.albicans genes
      reveals that CaNrg1 represses a subset of CaTup1-regulated genes, which includes
      known hypha-specific genes and other virulence factors. Most of these genes
      contain an Nrg1 response element (NRE) in their promoter. CaNrg1 interacts
      specifically with an NRE in vitro. Also, deletion of two NREs from the ALS8
      promoter releases it from Nrg1-mediated repression. Hence, CaNrg1 is a
      transcriptional repressor that appears to target CaTup1 to a distinct set of
      virulence-related functions, including yeast-hypha morphogenesis.

PMID- 11532939
TI  - NRG1, a repressor of filamentous growth in C.albicans, is down-regulated during
      filament induction.
AB  - In response to a variety of external signals, the fungal pathogen Candida
      albicans undergoes a transition between ellipsoidal single cells (blastospores)
      and filaments composed of elongated cells attached end-to-end. Here we identify a
      DNA-binding protein, Nrg1, that represses filamentous growth in Candida probably
      by acting through the co-repressor Tup1. nrg1 mutant cells are predominantly
      filamentous under non-filament-inducing conditions and their colony morphology
      resembles that of tup1 mutants. We also identify two filament-specific genes,
      ECE1 and HWP1, whose transcription is repressed by Nrg1 under non-inducing
      conditions. These genes constitute a subset of those under Tup1 control,
      providing further evidence that Nrg1 acts by recruiting Tup1 to target genes. We
      show that growth in serum at 37 degrees C, a potent inducer of filamentous
      growth, causes a reduction of NRG1 mRNA, suggesting that filamentous growth is
      induced by the down-regulation of NRG1. Consistent with this idea, expression of
      NRG1 from a non-regulated promoter partially blocks the induction of filamentous
      growth.

PMID- 11532940
TI  - Isolated lymphatic endothelial cells transduce growth, survival and migratory
      signals via the VEGF-C/D receptor VEGFR-3.
AB  - Vascular endothelial growth factor receptor-3 (VEGFR-3/Flt4) binds two known
      members of the VEGF ligand family, VEGF-C and VEGF-D, and has a critical function
      in the remodelling of the primary capillary vasculature of midgestation embryos.
      Later during development, VEGFR-3 regulates the growth and maintenance of the
      lymphatic vessels. In the present study, we have isolated and cultured stable
      lineages of blood vascular and lymphatic endothelial cells from human primary
      microvascular endothelium by using antibodies against the extracellular domain of
      VEGFR-3. We show that VEGFR-3 stimulation alone protects the lymphatic
      endothelial cells from serum deprivation-induced apoptosis and induces their
      growth and migration. At least some of these signals are transduced via a protein
      kinase C-dependent activation of the p42/p44 MAPK signalling cascade and via a
      wortmannin-sensitive induction of Akt phosphorylation. These results define the
      critical role of VEGF-C/VEGFR-3 signalling in the growth and survival of
      lymphatic endothelial cells. The culture of isolated lymphatic endothelial cells
      should now allow further studies of the molecular properties of these cells.

PMID- 11532941
TI  - Three-dimensional domain swapping in the folded and molten-globule states of
      cystatins, an amyloid-forming structural superfamily.
AB  - Cystatins, an amyloid-forming structural superfamily, form highly stable, domain
      swapped dimers at physiological protein concentrations. In chicken cystatin, the
      active monomer is a kinetic trap en route to dimerization, and any changes in
      solution conditions or mutations that destabilize the folded state shorten the
      lifetime of the monomeric form. In such circumstances, amyloidogenesis will start
      from conditions where a domain-swapped dimer is the most prevalent species.
      Domain swapping occurs by a rearrangement of loop I, generating the new
      intermonomer interface between strands 2 and 3. The transition state for
      dimerization has a high level of hydrophobic group exposure, indicating that
      gross conformational perturbation is required for domain swapping to occur.
      Dimerization also occurs when chicken cystatin is in its reduced, molten-globule
      state, implying that the organization of secondary structure in this state
      mirrors that in the folded state and that domain swapping is not limited to the
      folded states of proteins. Although the interface between cystatin-fold units is
      poorly defined for cystatin A, the dimers are the appropriate size to account for
      the electron-dense regions in amyloid protofilaments.

PMID- 11532942
TI  - Homophilic complex formation of MT1-MMP facilitates proMMP-2 activation on the
      cell surface and promotes tumor cell invasion.
AB  - Activation of proMMP-2 by MT1-MMP is considered to be a critical event in cancer
      cell invasion. In the activation step, TIMP-2 bound to MT1-MMP on the cell
      surface acts as a receptor for proMMP-2. Subsequently, adjacent TIMP-2-free MT1
      MMP activates the proMMP-2 in the ternary complex. In this study, we demonstrate
      that MT1-MMP forms a homophilic complex through the hemopexin-like (PEX) domain
      that acts as a mechanism to keep MT1-MMP molecules close together to facilitate
      proMMP-2 activation. Deletion of the PEX domain in MT1-MMP, or swapping the
      domain with the one derived from MT4-MMP, abolished the ability to activate
      proMMP-2 on the cell surface without affecting the proteolytic activities. In
      addition, expression of the mutant MT1-MMP lacking the catalytic domain (MT1PEX
      F) efficiently inhibited complex formation of the full-length enzymes and
      activation of pro MMP-2. Furthermore, expression of MT1PEX-F inhibited proMMP-2
      activation and Matrigel invasion activity of invasive human fibrosarcoma HT1080
      cells. These findings elucidate a new function of the PEX domain: regulating MT1
      MMP activity on the cell surface, which accelerates cellular invasiveness in the
      tissue.

PMID- 11532943
TI  - Wobble modification defect in tRNA disturbs codon-anticodon interaction in a
      mitochondrial disease.
AB  - We previously showed that in mitochondrial tRNA(Lys) with an A8344G mutation
      responsible for myoclonus epilepsy associated with ragged-red fibers (MERRF), a
      subgroup of mitochondrial encephalomyopathic diseases, the normally modified
      wobble base (a 2-thiouridine derivative) remains unmodified. Since wobble base
      modifications are essential for translational efficiency and accuracy, we used
      mitochondrial components to estimate the translational activity in vitro of
      purified tRNA(Lys) carrying the mutation and found no mistranslation of non
      cognate codons by the mutant tRNA, but almost complete loss of translational
      activity for cognate codons. This defective translation was not explained by a
      decline in aminoacylation or lowered affinity toward elongation factor Tu.
      However, when direct interaction of the codon with the mutant tRNA(Lys) defective
      anticodon was examined by ribosomal binding analysis, the wild-type but not the
      mutant tRNA(Lys) bound to an mRNA- ribosome complex. We therefore concluded that
      the anticodon base modification defect, which is forced by the pathogenic point
      mutation, disturbs codon- anticodon pairing in the mutant tRNA(Lys), leading to a
      severe reduction in mitochondrial translation that eventually could result in the
      onset of MERRF.

PMID- 11532944
TI  - The fragile X mental retardation protein binds specifically to its mRNA via a
      purine quartet motif.
AB  - Fragile X syndrome is caused by the absence of protein FMRP, the function of
      which is still poorly understood. Previous studies have suggested that FMRP may
      be involved in various aspects of mRNA metabolism, including transport, stability
      and/or translatability. FMRP was shown to interact with a subset of brain mRNAs
      as well as with its own mRNA; however, no specific RNA-binding site could be
      identified precisely. Here, we report the identification and characterization of
      a specific and high affinity binding site for FMRP in the RGG-coding region of
      its own mRNA. This site contains a purine quartet motif that is essential for
      FMRP binding and can be substituted by a heterologous quartet-forming motif. The
      specific binding of FMRP to its target site was confirmed further in a
      reticulocyte lysate through its ability to repress translation of a reporter gene
      harboring the RNA target site in the 5'-untranslated region. Our data address
      interesting questions concerning the role of FMRP in the post-transcriptional
      control of its own gene and possibly other target genes.

PMID- 11532946
TI  - Invertebrate connectin spans as much as 3.5 microm in the giant sarcomeres of
      crayfish claw muscle.
AB  - In crayfish claw closer muscle, the giant sarcomeres are 8.3 microm long at rest,
      four times longer than vertebrate striated muscle sarcomeres, and they are
      extensible up to 13 microm upon stretch. Invertebrate connectin (I-connectin) is
      an elastic protein which holds the A band at the center of the sarcomere. The
      entire sequence of crayfish I-connectin was predicted from cDNA sequences of 53
      424 bp (17 352 residues; 1960 kDa). Crayfish I-connectin contains two novel 68-
      and 71-residue repeats, and also two PEVK domains and one kettin region. Kettin
      is a small isoform of I-connectin. Immunoblot tests using antibody to the 68
      residue repeats revealed the presence of I-connectin also in long sarcomeres of
      insect leg muscle and barnacle ventral muscle. Immunofluorescence microscopy
      demonstrated that the two repeats, the long spacer and the two PEVK domains
      contribute to sarcomere extension. These regions rich in charged amino acids,
      occupying 63% of the crayfish I-connectin molecule, may allow a span of a 3.5
      microm distance as a new class of composite spring.

PMID- 11532945
TI  - The FK506-binding protein 25 functionally associates with histone deacetylases
      and with transcription factor YY1.
AB  - FK506-binding proteins (FKBPs) are cellular receptors for immunosuppressants that
      belong to a subgroup of proteins, known as immunophilins, with peptidylprolyl cis
      trans isomerase (PPIase) activity. Sequence comparison suggested that the HD2
      type histone deacetylases and the FKBP-type PPIases may have evolved from a
      common ancestor enzyme. Here we show that FKBP25 physically associates with the
      histone deacetylases HDAC1 and HDAC2 and with the HDAC-binding transcriptional
      regulator YY1. An FKBP25 immunoprecipitated complex contains deacetylase
      activity, and this activity is associated with the N-terminus of FKBP25, distinct
      from the FK506/rapamycin-binding domain. Furthermore, FKBP25 can alter the DNA
      binding activity of YY1. Together, our data firmly establish a relationship
      between histone deacetylases and the FKBP enzymes and provide a novel and
      critical function for the FKBPs.

PMID- 11532948
TI  - Translocation within the acceptor helix of a major tRNA identity determinant.
AB  - The genetic code is defined by the specific aminoacylations of tRNAs by aminoacyl
      tRNA synthetases. Although the synthetases are widely conserved through
      evolution, aminoacylation of a given tRNA is often system specific-a synthetase
      from one source will not acylate its cognate tRNA from another. This system
      specificity is due commonly to variations in the sequence of a critical tRNA
      identity element. In bacteria and the cytoplasm of eukaryotes, an acceptor stem
      G3:U70 base pair marks a tRNA for aminoacylation with alanine. In contrast,
      Drosophila melanogaster (Dm) mitochondrial (mt) tRNA(Ala) has a G2:U71 but not a
      G3:U70 pair. Here we show that this translocated G:U and the adjacent G3:C70 are
      major determinants for recognition by Dm mt alanyl-tRNA synthetase (AlaRS).
      Additionally, G:U at the 3:70 position serves as an anti-determinant for Dm mt
      AlaRS. Consequently, the mitochondrial enzyme cannot charge cytoplasmic
      tRNA(Ala). All insect mitochondrial AlaRSs appear to have split apart recognition
      of mitochondrial from cytoplasmic tRNA(Ala) by translocation of G:U. This split
      may be essential for preventing introduction of ambiguous states into the genetic
      code.

PMID- 11532947
TI  - Separate SCF(CDC4) recognition elements target Cdc6 for proteolysis in S phase
      and mitosis.
AB  - The Cdc6 DNA replication initiation factor is targeted for ubiquitin-mediated
      proteolysis by the E3 ubiquitin ligase SCF(CDC4) from the end of G1phase until
      mitosis in the budding yeast Saccharomyces cerevisiae. Here we describe a
      dominant-negative CDC6 mutant that, when overexpressed, arrests the cell cycle by
      inhibiting cyclin-dependent kinases (CDKs) and, thus, prevents passage through
      mitosis. This mutant protein inhibits CDKs more efficiently than wild-type Cdc6,
      in part because it is completely refractory to SCF(CDC4)-mediated proteolysis
      late in the cell cycle and consequently accumulates to high levels. The mutation
      responsible for this phenotype destroys a putative CDK phosphorylation site near
      the middle of the Cdc6 primary amino acid sequence. We show that this site lies
      within a novel Cdc4-interacting domain distinct from a Cdc4-interacting site
      identified previously near the N-terminus of the protein. We show that both sites
      can target Cdc6 for proteolysis in late G1/early S phase whilst only the newly
      identified site can target Cdc6 for proteolysis during mitosis.

PMID- 11532949
TI  - Repression of bacterial motility by a novel fimbrial gene product.
AB  - Proteus mirabilis is a common uropathogen in patients with long-term
      catheterization or with structural or functional abnormalities in the urinary
      tract. The mannose-resistant, Proteus-like (MR/P) fimbriae and flagellum are
      among virulence factors of P.mirabilis that contribute to its colonization in a
      murine model of ascending urinary tract infection. mrpJ, the last of nine genes
      of the mrp operon, encodes a 107 amino acid protein that contains a putative
      helix-turn-helix domain. Using transcriptional lacZ fusions integrated into the
      chromosome and mutagenesis studies, we demonstrate that MrpJ represses
      transcription of the flagellar regulon and thus reduces flagella synthesis when
      MR/P fimbriae are produced. The repression of flagella synthesis by MrpJ is
      confirmed by electron microscopy. However, a gel mobility shift assay indicates
      that MrpJ does not bind directly to the regulatory region of the flhDC operon.
      The isogenic mrpJ null mutant of wild-type P.mirabilis strain HI4320 is
      attenuated in the murine model. Our data also indicate that PapX encoded by a pap
      (pyelonephritis- associated pilus) operon of uropathogenic Escherichia coli is a
      functional homolog of MrpJ.

PMID- 11532950
TI  - Improvement of reading frame maintenance is a common function for several tRNA
      modifications.
AB  - Transfer RNAs from all organisms contain many modified nucleosides. Their vastly
      different chemical structures, their presence in different tRNAs, their
      occurrence in different locations in tRNA and their influence on different
      reactions in which tRNA participates suggest that each modified nucleoside may
      have its own specific function. However, since the frequency of frameshifting in
      several different mutants [mnmA, mnmE, tgt, truA (hisT), trmD, miaA, miaB and
      miaE] defective in tRNA modification was higher compared with the corresponding
      wild-type controls, these modifications have a common function: they all improve
      reading frame maintenance. Frameshifting occurs by peptidyl-tRNA slippage, which
      is influenced by the hypomodified tRNA in two ways: (i) a hypomodified tRNA in
      the ternary complex may decrease the rate by which the complex is recruited to
      the A-site and thereby increasing peptidyl-tRNA slippage; or (ii) a hypomodified
      peptidyl-tRNA may be more prone to slip than its fully modified counterpart. We
      propose that the improvement of reading frame maintenance has been and is the
      major selective factor for the emergence of new modified nucleosides.

PMID- 11532951
TI  - Heterologous, splicing-dependent RNA editing in chloroplasts: allotetraploidy
      provides trans-factors.
AB  - RNA editing is unique among post-transcriptional processes in plastids, as it
      exhibits extraordinary phylogenetic dynamics leading to species-specific editing
      site patterns. The evolutionary loss of a site is considered to entail the loss
      of the corresponding nuclear-encoded site-specific factor, which prevents the
      editing of foreign, i.e. heterologous, sites. We investigated the editing of
      short 'spliced' and 'unspliced' ndhA gene fragments from spinach in Nicotiana
      tabacum (tobacco) in vivo using biolistic transformation. Surprisingly, it turned
      out that the spinach site is edited in the heterologous nuclear background.
      Furthermore, only exon-exon fusions were edited, whereas intron-containing
      messages remained unprocessed. A homologue of the spinach site was found to be
      present and edited in Nicotiana tomentosiformis, representing the paternal
      parent, but absent from Nicotiana sylvestris, representing the maternal parent of
      tobacco. Our data show that: (i) the cis-determinants for ndhA editing are split
      by an intron; (ii) the editing capacity cannot be deduced from editing sites; and
      (iii) allopolyploidization can increase the editing capacity, which implies that
      it can influence speciation processes in evolution.

PMID- 11532952
TI  - Energetic contribution of non-essential 5' sequence to catalysis in a hepatitis
      delta virus ribozyme.
AB  - Hepatitis delta virus (HDV) ribozymes employ multiple catalytic strategies to
      achieve overall rate enhancement of RNA cleavage. These strategies include
      general acid-base catalysis by a cytosine side chain and involvement of divalent
      metal ions. Here we used a trans-acting form of the antigenomic ribozyme to
      examine the contribution of the 5' sequence in the substrate to HDV ribozyme
      catalysis. The cleavage rate constants increased for substrates with 5' sequence
      alterations that reduced ground-state binding to the ribozyme. Quantitatively, a
      plot of activation free energy of chemical conversion versus Gibb's free energy
      of substrate binding revealed a linear relationship with a slope of -1. This
      relationship is consistent with a model in which components of the substrate
      immediately 5' to the cleavage site in the HDV ribozyme-substrate complex
      destabilize ground-state binding. The intrinsic binding energy derived from the
      ground-state destabilization could contribute up to 2 kcal/mol toward the total
      8.5 kcal/mol reduction in activation free energy for RNA cleavage catalyzed by
      the HDV ribozyme.

PMID- 11532953
TI  - NoRC--a novel member of mammalian ISWI-containing chromatin remodeling machines.
AB  - Transcription by RNA polymerase I on nucleosomal templates requires binding of
      the transcription termination factor TTF-I to a cognate site 160 bp upstream of
      the transcription start site. Binding of TTF-I is accompanied by changes in the
      chromatin architecture which suggests that TTF-I recruits a remodeling activity
      to the rDNA promoter. We have cloned a cDNA that encodes TIP5 (TTF-I-interacting
      protein 5), a 205 kDa protein that shares a number of important protein domains
      with WSTF (Williams syndrome transcription factor) and hAcf1/WCRF180, the largest
      subunits of human chromatin remodeling complexes hCHRAC and WCRF. TIP5 co
      localizes with the basal RNA polymerase I transcription factor UBF in the
      nucleolus and is associated with SNF2h. The cellular TIP5-SNF2h complex, termed
      NoRC (nucleolar remodeling complex), induces nucleosome sliding in an ATP- and
      histone H4 tail-dependent fashion. The results suggest that NoRC is a novel
      nucleolar chromatin remodeling machine that may serve a role in the regulation of
      the rDNA locus.

PMID- 11532954
TI  - Probing the ATP-binding site of P1 ParA: partition and repression have different
      requirements for ATP binding and hydrolysis.
AB  - The ParA family of proteins is involved in partition of a variety of plasmid and
      bacterial chromosomes. P1 ParA plays two roles in partition: it acts as a
      repressor of the par operon and has an undefined yet indispensable role in P1
      plasmid localization. We constructed seven mutations in three putative ATP
      binding motifs of ParA. Three classes of phenotypes resulted, each represented by
      mutations in more than one motif. Three mutations created 'super-repressors', in
      which repressor activity was much stronger than in wild-type ParA, while the
      remainder damaged repressor activity. All mutations eliminated partition
      activities, but two showed a plasmid stability defect that was worse than that of
      a null mutation. Four mutant ParAs, two super-repressors and two weak repressors,
      were analyzed biochemically, and all exhibited damaged ATPase activity. The super
      repressors bound site-specifically to the par operator sequence, and this
      activity was strongly stimulated by ATP and ADP. These results support the
      proposal that ATP binding is essential but hydrolysis is inhibitory for ParA's
      repressor activity and suggest that ATP hydrolysis is essential for plasmid
      localization.

PMID- 11532955
TI  - Deregulated beta-catenin induces a p53- and ARF-dependent growth arrest and
      cooperates with Ras in transformation.
AB  - Aberrant activation of beta-catenin contributes to the onset of a variety of
      tumors. We report that a tumor-derived beta-catenin mutant induces accumulation
      and activation of the p53 tumor suppressor protein. Induction is mediated through
      ARF, an alternative reading frame product of the INK4A tumor suppressor locus, in
      a manner partially dependent on the transcription factor E2F1. In wild-type mouse
      embryo fibroblasts, mutant beta-catenin inhibits cell proliferation and imposes a
      senescence-like phenotype. This does not occur in cells lacking either ARF or
      p53, where deregulated beta-catenin actually overrides density-dependent growth
      inhibition and cooperates with activated Ras in transformation. Thus, the
      oncogenic activity of deregulated beta-catenin is curtailed by concurrent
      activation of the p53 pathway, thereby providing a protective mechanism against
      cancer. When the p53 pathway is impaired, deregulated beta-catenin is free to
      manifest its oncogenic features. This can occur not only by p53 mutations, but
      also by ablation of ARF expression, as observed frequently in early stages of
      colorectal carcinogenesis.

PMID- 11532956
TI  - Purification, cloning and characterization of a GPI inositol deacylase from
      Trypanosoma brucei.
AB  - Inositol acylation is an obligatory step in glycosylphosphatidylinositol (GPI)
      biosynthesis whereas mature GPI anchors often lack this modification. The GPI
      anchors of Trypanosoma brucei variant surface glycoproteins (VSGs) undergo rounds
      of inositol acylation and deacylation during GPI biosynthesis and the deacylation
      reactions are inhibited by diisopropylfluorophosphate (DFP). Inositol deacylase
      was affinity labelled with [3H]DFP and purified. Peptide sequencing was used to
      clone GPIdeAc, which encodes a protein with significant sequence and hydropathy
      similarity to mammalian acyloxyacyl hydrolase, an enzyme that removes fatty acids
      from bacterial lipopolysaccharide. Both contain a signal sequence followed by a
      saposin domain and a GDSL-lipase domain. GPIdeAc(-/-) trypanosomes were viable in
      vitro and in animals. Affinity-purified HA-tagged GPIdeAc was shown to have
      inositol deacylase activity. However, total inositol deacylase activity was only
      reduced in GPIdeAc(-/-) trypanosomes and the VSG GPI anchor was indistinguishable
      from wild type. These results suggest that there is redundancy in T.brucei
      inositol deacylase activity and that there is another enzyme whose sequence is
      not recognizably related to GPIdeAc.

PMID- 11532957
TI  - The chromatin remodelling factor Brg-1 interacts with beta-catenin to promote
      target gene activation.
AB  - Wnt-induced formation of nuclear Tcf-beta-catenin complexes promotes
      transcriptional activation of target genes involved in cell fate decisions.
      Inappropriate expression of Tcf target genes resulting from mutational activation
      of this pathway is also implicated in tumorigenesis. The C-terminus of beta
      catenin is indispensable for the transactivation function, which probably
      reflects the presence of binding sites for essential transcriptional coactivators
      such as p300/CBP. However, the precise mechanism of transactivation remains
      unclear. Here we demonstrate an interaction between beta-catenin and Brg-1, a
      component of mammalian SWI/SNF and Rsc chromatin-remodelling complexes. A
      functional consequence of reintroduction of Brg-1 into Brg-1-deficient cells is
      enhanced activity of a Tcf-responsive reporter gene. Consistent with this, stable
      expression of inactive forms of Brg-1 in colon carcinoma cell lines specifically
      inhibits expression of endogenous Tcf target genes. In addition, we observe
      genetic interactions between the Brg-1 and beta-catenin homologues in flies. We
      conclude that beta-catenin recruits Brg-1 to Tcf target gene promoters,
      facilitating chromatin remodelling as a prerequisite for transcriptional
      activation.

PMID- 11532958
TI  - Increasing the rate of chromatin remodeling and gene activation--a novel role for
      the histone acetyltransferase Gcn5.
AB  - Histone acetyltransferases (HATs) such as Gcn5 play a role in transcriptional
      activation. However, the majority of constitutive genes show no requirement for
      GCN5, and even regulated genes, such as the yeast PHO5 gene, do not seem to be
      affected significantly by its absence under normal activation conditions. Here we
      show that even though the steady-state level of activated PHO5 transcription is
      not affected by deletion of GCN5, the rate of activation following phosphate
      starvation is significantly decreased. This delay in transcriptional activation
      is specifically due to slow chromatin remodeling of the PHO5 promoter, whereas
      the transmission of the phosphate starvation signal to the PHO5 promoter
      progresses at a normal rate. Chromatin remodeling is equally delayed in a
      galactose-inducible PHO5 promoter variant in which the Pho4 binding sites have
      been replaced by Gal4 binding sites. By contrast, activation of the GAL1 gene by
      galactose addition occurs with normal kinetics. Lack of the histone H4 N-termini
      leads to a similar delay in activation of the PHO5 promoter. These results
      indicate that one important contribution of HATs is to increase the rate of gene
      induction by accelerating chromatin remodeling, rather than to affect the final
      steady-state expression levels.

PMID- 11532959
TI  - A moving DNA replication factory in Caulobacter crescentus.
AB  - The in vivo intracellular location of components of the Caulobacter replication
      apparatus was visualized during the cell cycle. Replisome assembly occurs at the
      chromosomal origin located at the stalked cell pole, coincident with the
      initiation of DNA replication. The replisome gradually moves to midcell as DNA
      replication proceeds and disassembles upon completion of DNA replication.
      Although the newly replicated origin regions of the chromosome are rapidly moved
      to opposite cell poles by an active process, the replisome appears to be an
      untethered replication factory that is passively displaced towards the center of
      the cell by the newly replicated DNA. These results are consistent with a model
      in which unreplicated DNA is pulled into the replication factory and newly
      replicated DNA is bidirectionally extruded from the complex, perhaps contributing
      to chromosome segregation.

PMID- 11532960
TI  - Structure of the ABC ATPase domain of human TAP1, the transporter associated with
      antigen processing.
AB  - The transporter associated with antigen processing (TAP) is an ABC transporter
      formed of two subunits, TAP1 and TAP2, each of which has an N-terminal membrane
      spanning domain and a C-terminal ABC ATPase domain. We report the structure of
      the C-terminal ABC ATPase domain of TAP1 (cTAP1) bound to ADP. cTAP1 forms an L
      shaped molecule with two domains, a RecA-like domain and a small alpha-helical
      domain. The diphosphate group of ADP interacts with the P-loop as expected.
      Residues thought to be involved in gamma-phosphate binding and hydrolysis show
      flexibility in the ADP-bound state as evidenced by their high B-factors.
      Comparisons of cTAP1 with other ABC ATPases from the ABC transporter family as
      well as ABC ATPases involved in DNA maintenance and repair reveal key regions and
      residues specific to each family. Three ATPase subfamilies are identified which
      have distinct adenosine recognition motifs, as well as distinct subdomains that
      may be specific to the different functions of each subfamily. Differences between
      TAP1 and TAP2 in the nucleotide-binding site may be related to the observed
      asymmetry during peptide transport.

PMID- 11532961
TI  - An essential role for ARF6-regulated membrane traffic in adherens junction
      turnover and epithelial cell migration.
AB  - We describe a novel role for the ARF6 GTPase in the regulation of adherens
      junction (AJ) turnover in MDCK epithelial cells. Expression of a GTPase-defective
      ARF6 mutant, ARF6(Q67L), led to a loss of AJs and ruffling of the lateral plasma
      membrane via mechanisms that were mutually exclusive. ARF6-GTP-induced AJ
      disassembly did not require actin remodeling, but was dependent on the
      internalization of E-cadherin into the cytoplasm via vesicle transport. ARF6
      activation was accompanied by increased migratory potential, and treatment of
      cells with hepatocyte growth factor (HGF) induced the activation of endogenous
      ARF6. The effect of ARF6(Q67L) on AJs was specific since ARF6 activation did not
      perturb tight junction assembly or cell polarity. In contrast, dominant-negative
      ARF6, ARF6(T27N), localized to AJs and its expression blocked cell migration and
      HGF-induced internalization of cadherin-based junctional components into the
      cytoplasm. Finally, we show that ARF6 exerts its role downstream of v-Src
      activation during the disassembly of AJs. These findings document an essential
      role for ARF6- regulated membrane traffic in AJ disassembly and epithelial cell
      migration.

PMID- 11532962
TI  - The exon-exon junction complex provides a binding platform for factors involved
      in mRNA export and nonsense-mediated mRNA decay.
AB  - We recently reported that spliceosomes alter messenger ribonucleoprotein particle
      (mRNP) composition by depositing several proteins 20-24 nucleotides upstream of
      mRNA exon-exon junctions. When assembled in vitro, this so-called 'exon-exon
      junction complex' (EJC) contains at least five proteins: SRm160, DEK, RNPS1, Y14
      and REF. To better investigate its functional attributes, we now describe a
      method for generating spliced mRNAs both in vitro and in vivo that either do or
      do not carry the EJC. Analysis of these mRNAs in Xenopus laevis oocytes revealed
      that this complex is the species responsible for enhancing nucleocytoplasmic
      export of spliced mRNAs. It does so by providing a strong binding site for the
      mRNA export factors REF and TAP/p15. Moreover, by serving as an anchoring point
      for the factors Upf2 and Upf3, the EJC provides a direct link between splicing
      and nonsense-mediated mRNA decay. Finally, we show that the composition of the
      EJC is dynamic in vivo and is subject to significant evolution upon mRNA export
      to the cytoplasm.

PMID- 11532963
TI  - Beat-to-beat oscillations of mitochondrial [Ca2+] in cardiac cells.
AB  - The Ca2+-sensitive photoprotein aequorin and the new green fluorescent protein
      based fluorescent Ca2+ indicators 'ratiometric-pericam' were selectively
      expressed in the mitochondria, cytosol and/or nucleus of spontaneously beating
      ventricular myocytes from neonatal rats. This combined strategy reveals that
      mitochondrial [Ca2+] oscillates rapidly and in synchrony with cytosolic and
      nuclear [Ca2+]. The Ca2+ oscillations were reduced in frequency and/or amplitude
      by verapamil and carbachol and were enhanced by isoproterenol and elevation of
      extracellular [Ca2+]. An increased frequency and/or amplitude of cytosolic Ca2+
      spikes was rapidly mirrored by similar changes in mitochondrial Ca2+ spikes and
      more slowly by elevations of the interspike Ca2+ levels. The present data
      unequivocally demonstrate that in cardiac cells mitochondrial [Ca2+] oscillates
      synchronously with cytosolic [Ca2+] and that mitochondrial Ca2+ handling rapidly
      adapts to inotropic or chronotropic inputs.

PMID- 11532964
TI  - Hrs recruits clathrin to early endosomes.
AB  - The hepatocyte growth factor-regulated tyrosine kinase substrate, Hrs, has been
      implicated in intracellular trafficking and signal transduction. Hrs contains a
      phosphatidylinositol 3-phosphate-binding FYVE domain that contributes to its
      endosomal targeting. Here we show that Hrs and EEA1, a FYVE domain protein
      involved in endocytic membrane fusion, are localized to different regions of
      early endosomes. We demonstrate that Hrs co-localizes with clathrin, and that the
      C-terminus of Hrs contains a functional clathrin box motif that interacts
      directly with the terminal beta-propeller domain of clathrin heavy chain. A
      massive recruitment of clathrin to early endosomes was observed in cells
      transfected with Hrs, but not with Hrs lacking the C-terminus. Furthermore, the
      phosphatidylinositol 3-kinase inhibitor wortmannin caused the dissociation of
      both Hrs and clathrin from endosomes. While overexpression of Hrs did not affect
      endocytosis and recycling of transferrin, endocytosed epidermal growth factor and
      dextran were retained in early endosomes. These results provide a molecular
      mechanism for the recruitment of clathrin onto early endosomes and suggest a
      function for Hrs in trafficking from early to late endosomes.

PMID- 11532966
TI  - Glycan-dependent signaling: O-linked N-acetylglucosamine.
AB  - The addition of O-linked N-acetylglucosamine (O-GlcNAc) to target proteins may
      serve as a signaling modification analogous to protein phosphorylation. Like
      phosphorylation, O-GlcNAc is a dynamic modification occurring in the nucleus and
      cytoplasm. Various analytical methods have been developed to detect O-GlcNAc and
      distinguish it from glycosylation in the endomembrane system. Many target
      molecules have been identified; these targets are typically components of
      supramolecular complexes such as transcription factors, nuclear pore proteins, or
      cytoskeletal components. The enzymes responsible for O-GlcNAc addition and
      removal are highly conserved molecules having molecular features consistent with
      a signaling role. The O-GlcNAc transferase and O-GlcNAcase are likely to act in
      consort with kinases and phosphatases generating various isoforms of
      physiological substrates. These isoforms may differ in such properties as protein
      protein interactions, protein stability, and enzymatic activity. Since O-GlcNAc
      plays a critical role in the regulation of signaling pathways of higher plants,
      the glycan modification is likely to perform similar signaling functions in
      mammalian cells. Glucose and amino acid metabolism generates hexosamine
      precursors that may be key regulators of a nutrient sensing pathway involving O
      GlcNAc signaling. Altered O-linked GlcNAc metabolism may also occur in human
      diseases including neurodegenerative disorders, diabetes mellitus and cancer.

PMID- 11532965
TI  - The Usf-1 transcription factor is a novel target for the stress-responsive p38
      kinase and mediates UV-induced Tyrosinase expression.
AB  - The stress-activated signalling cascade leading to phosphorylation of the p38
      family of kinases plays a crucial role during development and in the cellular
      response to a wide variety of stress-inducing agents. Although alterations in
      gene expression characteristic of the stress response require the regulation of
      key transcription factors by the p38 family, few downstream targets for this
      signalling pathway have been identified. By examining the ability of pigment
      cells to respond to UV irradiation as part of the UV-induced tanning response, we
      show that while the microphthalmia-associated transcription factor Mitf regulates
      basal Tyrosinase expression, it is the ubiquitous basic helix-loop-helix-leucine
      zipper transcription factor Usf-1 that is required for the UV activation of the
      Tyrosinase promoter. Consistent with this we demonstrate that Usf-1 is
      phosphorylated and activated by the stress-responsive p38 kinase. The results
      suggest that activation of Usf-1 by p38 at a wide variety of viral and cellular
      promoters will provide a link between stimuli as diverse as UV irradiation,
      glucose, viral infection and pro-inflammatory cytokines, and the changes in gene
      expression associated with the stress response.

PMID- 11532967
TI  - Overexpression of p27(Kip1) by doxycycline-regulated adenoviral vectors inhibits
      endothelial cell proliferation and migration and impairs angiogenesis.
AB  - Formation of new blood vessels in the adult animal (i.e., angiogenesis) is an
      important event for tissue repair and for tumor growth and metastasis.
      Angiogenesis involves the migration and proliferation of endothelial cells. We
      have investigated the role of the growth suppressor p27(Kip1) (p27) on
      endothelial cell function in vitro and angiogenesis in vivo. We have generated Ad
      TetON, a replication-deficient adenovirus that constitutively expresses the
      reverse tet-responsive transcriptional activator, and Ad-TRE-p27, which drives
      expression of p27 under the control of the tet response element. Western blot
      analysis demonstrated doxycycline-dependent overexpression of p27 in human
      umbilical vein endothelial cells (HUVECs) coinfected with Ad-TetON and Ad-TRE
      p27, which resulted in a marked inhibition of DNA replication and cell migration
      in vitro. Inducible overexpression of p27 in cultured HUVECs inhibited the
      formation of tubelike structures and, when applied in a murine model of hind limb
      ischemia, reduced hind limb blood flow recovery and capillary density. These
      findings thus underscore a novel role of p27 in regulating endothelial cell
      migration in vitro and angiogenesis in vivo, suggesting a novel anti-angiogenic
      therapy based on inducible p27 overexpression.

PMID- 11532968
TI  - A novel cardioprotective role of RhoA: new signaling mechanism for adenosine.
AB  - Adenosine exerts a potent cardioprotective effect that is mediated by adenosine
      A1 and A3 receptors. The signaling pathways activated by the A1 and A3 receptors
      are distinct and involve selective coupling to phospholipases C and D,
      respectively. The objective of our study was to elucidate the signaling mechanism
      that mediates the coupling of each receptor to its respective phospholipase and
      to test the role of RhoA as a novel mediator leading from adenosine receptors to
      cardioprotection. C3 transferase and dominant negative RhoA (RhoAT19N) blocked
      the A3 receptor-mediated phospholipase D activation and cardioprotection but had
      no effect on A1 receptor-mediated phospholipase C activation or cardioprotection.
      In contrast, pertussis toxin treatment caused a greater inhibition of the
      diacylglycerol accumulation induced by the A1 agonist than by the A3 agonist, and
      it completely abrogated the A1 agonist-mediated cardioprotection. Thus, adenosine
      A1 and A3 receptors are linked to different G-proteins. The A3 receptor is
      coupled via RhoA to activate phospholipase D in exerting its cardioprotective
      effect, whereas the A1 receptor is linked via Gi to phospholipase C to produce
      cardioprotective responses. The present study identifies a novel role for RhoA
      and further suggests its importance in regulating cardiac cellular function.

PMID- 11532969
TI  - Evidence for Ca2+- and ATP-sensitive peripheral channels in nuclear pore
      complexes.
AB  - In eukaryotic cells the nuclear envelope (NE) serves as a functional barrier
      between cytosol and nucleoplasm perforated by nuclear pore complexes (NPCs). Both
      active and passive transport of ions and macromolecules are thought to be
      mediated by the centrally located large NPC channel. However, 3-dimensional
      imaging of NPCs based on electron microscopy indicates the existence of
      additional small channels of unknown function located in the NPC periphery. By
      means of the recently developed nuclear hourglass technique that measures NE
      electrical conductance, we evaluated passive electrically driven transport
      through NPCs. In isolated Xenopus laevis oocyte nuclei, we varied ambient Ca2+
      and ATP in the cytosolic solution and/or chelated Ca2+ in the perinuclear stores
      in order to assess the role of Ca2+ in regulating passive ion transport. We
      noticed that NE electrical conductance is large under conditions where
      macromolecule permeability is known to be low. In addition, atomic force
      microscopy applied to native NPCs detects multiple small pores in the NPC
      periphery consistent with channel openings. Peripheral pores were detectable only
      in the presence of ATP. We conclude that NPC transport of ions and macromolecules
      occurs through different routes. We present a model in which NE ion flux does not
      occur through the central NPC channel but rather through Ca2+- and ATP-activated
      peripheral channels of individual NPCs.

PMID- 11532970
TI  - Deoxythioguanosine triphosphate impairs HIV replication: a new mechanism for an
      old drug.
AB  - Inhibition of HIV-1 reverse transcriptase (RT) and HIV protease are effective
      mechanisms for anti-retroviral agents, and the combined use of mechanistically
      different medications has markedly improved the treatment of HIV infected
      patients. The active metabolite of mercaptopurine and thioguanine (TG),
      deoxythioguanosine triphosphate, was shown to be incorporated into DNA by the
      polymerase function of HIV-1 RT and then to abrogate RNA cleavage by HIV-1
      RNaseH. Treatment of human lymphocyte cultures with thioguanine produced
      substantial inhibition of HIV replication (IC(50)=0.035 microM, IC(95)=15.4
      microM), with minimal toxicity to host lymphocytes (<10% at 15.4 microM TG,
      P<0.000005). Furthermore, low concentrations of TG and zidovudine were
      synergistic in inhibiting HIV replication in human lymphocytes (synergy volume=19
      microM(2)%), without additive cytotoxicity to host lymphocytes. Thus, thiopurines
      are novel anti-retroviral agents that alter the DNA-RNA substrates for HIV
      RNaseH, thereby abrogating early stages of HIV replication.

PMID- 11532971
TI  - Angiotensin II activates Akt/protein kinase B by an arachidonic acid/redox
      dependent pathway and independent of phosphoinositide 3-kinase.
AB  - Angiotensin II (Ang II) exerts contractile and trophic effects in glomerular
      mesangial cells (MCs). One potential downstream target of Ang II is the protein
      kinase Akt/protein kinase B (PKB). We investigated the effect of Ang II on
      Akt/PKB activity in MCs. Ang II causes rapid activation of Akt/PKB (5-10 min) but
      delayed activation of phosphoinositide 3-kinase (PI3-K) (30 min). Activation of
      Akt/PKB by Ang II was not abrogated by the PI3-K inhibitors or by the
      introduction of a dominant negative PI3-K, indicating that in MCs, PI3-K is not
      an upstream mediator of Akt/PKB activation by Ang II. Incubation of MCs with
      phospholipase A2 inhibitors also blocked Akt/PKB activation by Ang II. AA
      mimicked the effect of Ang II. Inhibitors of cyclooxygenase-, lipoxyogenase-, and
      cytochrome P450-dependent metabolism did not influence AA-induced Akt/PKB
      activation. However, the antioxidants N-acetylcysteine and diphenylene iodonium
      inhibited both AA- and Ang II-induced Akt/PKB activation. Dominant negative
      mutant of Akt/PKB or antioxidants, but not the dominant negative form of PI3-K,
      inhibited Ang II-induced protein synthesis and cell hypertrophy. These data
      provide the first evidence that Ang II induces protein synthesis and hypertrophy
      in MCs through AA/redox-dependent pathway and Akt/PKB activation independent of
      PI3-K.

PMID- 11532972
TI  - Beta-adrenergic receptors (betaAR) regulate cardiomyocyte proliferation during
      early postnatal life.
AB  - Cardiomyocyte development switches from hyperplasmic to hypertrophic growth
      between postnatal days 3 and 4 in rats. The mechanisms responsible for this
      transition have been controversial. beta-Adrenergic receptor (betaAR) activation
      of mitogenic responses in vitro has been reported. We hypothesized that tonic
      activation of the betaAR signaling regulates cell division in neonatal
      cardiomyocytes via effects on signaling kinases known to be important in cell
      cycle regulation. The purpose of the current study was to elucidate the roles of
      betaAR in rat cardiomyocyte growth in vivo. We demonstrated that betaAR blockade
      induced a significant reduction in cardiomyocyte proliferation as measured by the
      BrdU labeling index. Blockade of betaAR did not affect p38 or p44/42 MAPK
      activities. We further demonstrated that betaAR blockade induced a prompt
      deactivation of the p70 ribosomal protein S6 kinase (p70 S6K). To confirm these
      results, we measured p70 S6K activity directly. Basal activity of p70 S6K in
      neonatal cardiomyocytes was fourfold higher than that of insulin-treated adult
      rat liver. The activity of p70 S6K was reduced by 60% within 1 min after betaAR
      blockade. We conclude that the betaAR are involved in regulation of neonatal
      cardiomyocyte proliferation and that this mitogenic control may be mediated via
      the p70 S6K pathway.

PMID- 11532973
TI  - Efficiency of homocysteine plus copper in inducing apoptosis is inversely
      proportional to gamma-glutamyl transpeptidase activity.
AB  - Hyperhomocysteinemia represents an independent risk factor for atherosclerosis,
      but the mechanisms leading to cellular dysfunctions remain unknown. Using ECV304
      cells, we found that homocysteine (Hcy) plus copper (Cu2+) induced cytotoxic
      effects: loss of cell adhesion, increased permeability to PI, and the occurrence
      of morphologically apoptotic cells. This form of apoptosis, inhibited by Z-VAD
      fmk, was associated with a loss of mitochondrial potential, a cytosolic release
      of cytochrome c, activation of caspase-3, degradation of poly(ADP
      ribose)polymerase, and internucleosomal DNA fragmentation. However, the ability
      of Hcy plus Cu2+ to induce apoptosis decreased when the pretreatment culture time
      increased. As a positive correlation was found between the length of time of
      culture before treatment and the enhancement of gamma-glutamyl transpeptidase
      (gamma-GT) activity, we asked whether gamma-GT was involved in the control of Hcy
      plus Cu2+-induced apoptosis. Therefore, ECV304 cells were treated with either
      acivicin or dexamethasone, inhibiting and stimulating gamma-GT, respectively. In
      ECV304 cells and human umbilical venous endothelial cells, acivicin favored Hcy
      plus Cu2+-induced apoptosis whereas dexamethasone counteracted the apoptotic
      process. As acivicin and dexamethasone were also capable of modulating cell death
      in ECV304 cells treated with antitumoral drugs, our data emphasize that the
      involvement of gamma-GT in the control of apoptosis is not restricted to Hcy but
      also concerns other chemical compounds.

PMID- 11532974
TI  - High density lipoproteins reduce organ injury and organ dysfunction in a rat
      model of hemorrhagic shock.
AB  - High density lipoproteins (HDLs) inhibit the cytokine-induced expression of
      endothelial cell adhesion molecules both in vitro and in vivo. We examined the
      ability of HDLs to mediate a functional anti-inflammatory effect by measuring
      their ability to prevent neutrophil adhesion and transmigration in vitro.
      Treatment of human endothelial cell cultures with physiologic concentrations of
      HDLs inhibited neutrophil binding by 68 +/- 5.9% (mean and se, n=6, P<0.05) and
      neutrophil transmigration by 48.7 +/- 6.7% (n=8, P<0.05). We then examined the
      effect of HDLs on inflammatory infiltration and subsequent multiple organ
      dysfunction syndrome (MODS), associated with trauma in a rat model of hemorrhagic
      shock. Rats given human HDLs (80 mg apo A-I/kg, i.v.) 90 min after hemorrhage
      (which reduced mean arterial pressure to 50 mmHg) and 1 min before resuscitation
      showed attenuation of the increases in the serum levels of markers of MODS
      normally observed in this model. Severe disruption of the architecture of tissues
      and the extensive cellular infiltration into those tissues were also largely
      inhibited in animals that received HDLs. Human HDLs attenuate the MODS associated
      with ischemia and reperfusion injury after hemorrhagic shock in rats.

PMID- 11532975
TI  - Akt/PKB promotes cancer cell invasion via increased motility and
      metalloproteinase production.
AB  - The Akt/protein kinase B (PKB) serine/threonine kinase is well known as an
      important mediator of many cell survival signaling pathways. Here, we demonstrate
      for the first time a major role of Akt/PKB in the cell invasion properties of the
      highly metastatic cell line HT1080. Using confocal microscopic analyses of live
      samples, we found Akt/PKB to be localized in the leading edge membrane area of
      migrating HT1080 cells. This localization was dependent on phosphoinositide 3
      kinase and required the lipid binding ability of the phosphoinositide binding
      pleckstrin homology domain of Akt/PKB. We examined the possible function of
      Akt/PKB in HT1080 invasion. Surprisingly, Akt/PKB potently promoted HT1080
      invasion, by increasing cell motility and matrix metalloproteinase-9 (MMP-9)
      production, in a manner highly dependent on its kinase activity and membrane
      translocating ability. The increase in MMP-9 production was mediated by
      activation of nuclear factor-kappaB transcriptional activity by Akt/PKB. However,
      Akt/PKB did not affect the cell-cell or cell-matrix adhesion properties of
      HT1080. Our findings thus establish Akt/PKB as a major factor in the invasive
      abilities of cancer cells.

PMID- 11532976
TI  - Expression and function of adenosine receptors in human dendritic cells.
AB  - Dendritic cells (DCs) are specialized antigen-presenting cells characterized by
      their ability to migrate into target sites, process antigens, and activate naive
      T cells. In this study, we analyzed the biological activity and intracellular
      signaling of adenosine by using reverse transcriptase-polymerase chain reaction
      assays to investigate mRNA expression of A(1), A(2a) and A(3) adenosine receptors
      in immature and mature human DCs. Functional experiments on adenosine stimulation
      showed chemotaxis, intracellular calcium transients, and actin polymerization,
      but no activation of adenylate cyclase in immature DCs. Experiments with receptor
      isotype-selective agonists and antagonists as well as pertussis toxin revealed
      that chemotaxis, calcium transients, and actin polymerization were mediated via
      G(i-) or G(0-)protein-coupled A(1) and A(3) receptors. Maturation of DCs induced
      by lipopolysaccharide (LPS) resulted in down-regulation of A(1) and A(3) receptor
      mRNAs, although A(2a) receptor mRNA was still expressed. However, in LPS
      differentiated DCs, adenosine and an A(2a) receptor agonist stimulated adenylate
      cyclase activity, enhanced intracellular cAMP levels, and inhibited interleukin
      12 (IL-12) production. These effects could be completely prevented by
      pretreatment with A(2) receptor antagonist. These findings strongly suggest that
      adenosine has important but distinct biological effects in DCs activity as a
      chemotaxin for immature DCs and as a modulator of IL-12 production in mature DCs.
      These effects can be explained by differential expression of adenosine receptor
      subtypes.

PMID- 11532977
TI  - The peroxisome proliferator-activated receptor alpha regulates amino acid
      metabolism.
AB  - The peroxisome proliferator-activated receptor alpha is a ligand-activated
      transcription factor that plays an important role in the regulation of lipid
      homeostasis. PPARalpha mediates the effects of fibrates, which are potent
      hypolipidemic drugs, on gene expression. To better understand the biological
      effects of fibrates and PPARalpha, we searched for genes regulated by PPARalpha
      using oligonucleotide microarray and subtractive hybridization. By comparing
      liver RNA from wild-type and PPARalpha null mice, it was found that PPARalpha
      decreases the mRNA expression of enzymes involved in the metabolism of amino
      acids. Further analysis by Northern blot revealed that PPARalpha influences the
      expression of several genes involved in trans- and deamination of amino acids,
      and urea synthesis. Direct activation of PPARalpha using the synthetic PPARalpha
      ligand WY14643 decreased mRNA levels of these genes, suggesting that PPARalpha is
      directly implicated in the regulation of their expression. Consistent with these
      data, plasma urea concentrations are modulated by PPARalpha in vivo. It is
      concluded that in addition to oxidation of fatty acids, PPARalpha also regulates
      metabolism of amino acids in liver, indicating that PPARalpha is a key controller
      of intermediary metabolism during fasting.

PMID- 11532978
TI  - Macrophages require different nucleoside transport systems for proliferation and
      activation.
AB  - To evaluate the mechanisms involved in macrophage proliferation and activation,
      we studied the regulation of the nucleoside transport systems. In murine bone
      marrow-derived macrophages, the nucleosides required for DNA and RNA synthesis
      are recruited from the extracellular medium. M-CSF induced macrophage
      proliferation and DNA and RNA synthesis, whereas interferon gamma (IFN-gamma) led
      to activation, blocked proliferation, and induced only RNA synthesis. Macrophages
      express at least the concentrative systems N1 and N2 (CNT2 and CNT1 genes,
      respectively) and the equilibrative systems es and ei (ENT1 and ENT2 genes,
      respectively). Incubation with M-CSF only up-regulated the equilibrative system
      es. Inhibition of this transport system blocked M-CSF-dependent proliferation.
      Treatment with IFN-gamma only induced the concentrative N1 and N2 systems. IFN
      gamma also down-regulated the increased expression of the es equilibrative system
      induced by M-CSF. Thus, macrophage proliferation and activation require selective
      regulation of nucleoside transporters and may respond to specific requirements
      for DNA and RNA synthesis. This report also shows that the nucleoside
      transporters are critical for macrophage proliferation and activation.

PMID- 11532979
TI  - The growth suppressor p27(Kip1) protects against diet-induced atherosclerosis.
AB  - The molecular basis of atherosclerosis is associated with excessive proliferation
      of vascular cells. Previous studies have suggested an inverse correlation between
      the expression of the growth suppressor p27(Kip1) (p27) and cellular
      proliferation within human atherosclerotic tissue. However, no causal link
      between diminished p27 expression and atherogenesis has been established. We
      investigated the effect of p27 inactivation on diet-induced atherogenesis. We
      find that p27-deficient mice challenged with a high-fat diet for 1 month remain
      normocholesterolemic and have essentially no visible atheromas. However, when
      generated in an apolipoprotein E-null genetic background that leads to severe
      hypercholesterolemia in response to the atherogenic diet, deletion of p27
      enhances arterial cell proliferation (approximately fourfold) and accelerates
      atherogenesis (approximately sixfold) compared with apolipoprotein E-deficient
      mice with an intact p27 gene. Analysis of apolipoprotein E-null mice bearing only
      one p27 allele inactivated reveals that a moderate decrease in p27 protein
      expression in the setting of hypercholesterolemia is sufficient to predispose to
      atherogenesis. Thus, our study establishes a molecular link between decreased p27
      protein expression and atherogenesis in hypercholesterolemic animals.

PMID- 11532980
TI  - Rationale for the existence of additional adipostatic hormones.
AB  - Parabiosis studies with obese rodents demonstrated that circulating factors are
      involved in the long-term control of food intake and energy balance. More than 40
      years ago it was hypothesized that rats made obese by hypothalamic or dietary
      means, as well as genetically obese fa/fa rats and db/db mice, produce a
      circulating factor that either inhibits food intake or acts metabolically to
      reduce the fat content of non-obese ad libitum-fed partners. However, none of
      these obese rodents showed a significant change in weight when parabiosed to a
      normal animal. It was therefore postulated that these obese rodents produced a
      circulating lipostatic factor but were unable to respond to it. In contrast,
      genetically obese ob/ob mice were thought to be deficient in the circulating
      signal, as they lost weight when parabiosed to lean or obese db/db mice. The
      discovery of leptin suggested that the circulating lipostatic signal had been
      identified. However, a closer look at the outcome of the parabiotic studies
      reveals that leptin alone does not explain all of the findings of the parabiotic
      experiments. Another (or more than one) as yet unidentified factor(s) may be
      involved in energy balance regulation. The evidence for the existence of further
      leptin-like hormones comes from observations in which the direct effect of leptin
      has been eliminated or can be excluded.

PMID- 11532981
TI  - Divergent evolution in M6P/IGF2R imprinting from the Jurassic to the Quaternary.
AB  - M6P/IGF2R imprinting first appeared approximately 150 million years ago following
      the divergence of prototherian from therian mammals. Although M6P/IGF2R is
      clearly imprinted in opossums and rodents, its imprint status in humans remains
      ambiguous. It is also still unknown if M6P/IGF2R imprinting was an ancestral
      mammalian epigenotype or if it evolved convergently. We report herein that
      M6P/IGF2R is imprinted in Artiodactyla, as it is in Rodentia and Marsupialia, but
      that it is not imprinted in Scandentia, Dermoptera and Primates, including
      ringtail lemurs and humans. These results are most parsimonious with a single
      ancestral origin of M6P/IGF2R imprinting followed by a lineage-specific
      disappearance of M6P/IGF2R imprinting in Euarchonta. The absence of M6P/IGF2R
      imprinting in extant primates, due to its disappearance from the primate lineage
      over 75 million years ago, demonstrates that imprinting at this locus does not
      predispose to human disease. Moreover, the divergent evolution of M6P/IGF2R
      imprinting predicts that the success of in vitro embryo procedures such as
      cloning may be species dependent.

PMID- 11532982
TI  - Quantitative localization of heterogeneous methyl-CpG-binding protein 2 (MeCP2)
      expression phenotypes in normal and Rett syndrome brain by laser scanning
      cytometry.
AB  - Rett syndrome (RTT) is an X-linked, dominant neurodevelopmental disorder caused
      by mutations in MECP2, encoding the methyl-CpG-binding protein 2 (MeCP2). A major
      paradox in the pathogenesis of RTT is how mutations in ubiquitously transcribed
      MECP2 result in a phenotype specific to the central nervous system (CNS) during
      postnatal development. To address this question, we have used a novel approach
      for quantitating the level and distribution of wild-type and mutant MeCP2 in situ
      by immunofluorescence and laser scanning cytometry. Surprisingly, cellular
      heterogeneity in MeCP2 expression level was observed in normal brain with a
      subpopulation of cells exhibiting high expression (MeCP2(hi)) and the remainder
      exhibiting low expression (MeCP2(lo)). MeCP2 expression was significantly higher
      in CNS compared with non-CNS tissues of human and mouse by automated quantitation
      of MeCP2 on multiple tissue arrays. Quantitative localization of MeCP2 expression
      phenotypes in normal human brain showed a mosaic, but distinct, distribution
      pattern, with MeCP2(hi) neurons highest in layer IV of the cerebrum and MeCP2(lo
      )neurons highest in the granular layer of the cerebellum. In female RTT brains,
      MECP2 mutant-expressing cells were identified as cells negative for the MeCP2 C
      terminal epitope. MECP2 mutant-expressing cells were randomly localized in Rett
      cerebrum and cerebellum and showed normal MeCP2 expression with N-terminal
      specific anti-MeCP2. These results demonstrate a CNS-specific cellular phenotype
      of MeCP2 high expression and suggest that MECP2 mutations in RTT are only
      manifested in MeCP2(hi) cells. In addition, our results demonstrate the power of
      laser scanning cytometry in examining complex cellular phenotypes in disease
      pathogenesis.

PMID- 11532983
TI  - Fumarylacetoacetate, the metabolite accumulating in hereditary tyrosinemia,
      activates the ERK pathway and induces mitotic abnormalities and genomic
      instability.
AB  - Patients suffering from the metabolic disease hereditary tyrosinemia type I
      (HT1), caused by fumarylacetoacetate hydrolase deficiency, have a high risk of
      developing liver cancer. We report that a sub-apoptogenic dose of
      fumarylacetoacetate (FAA), the mutagenic metabolite accumulating in HT1, induces
      spindle disturbances and segregational defects in both rodent and human cells.
      Mitotic abnormalities, such as distorted spindles, lagging chromosomes,
      anaphase/telophase chromatin bridges, aberrant karyokinesis/cytokinesis and
      multinucleation were observed. Some mitotic asters displayed a large
      pericentriolar material cloud and/or altered distribution of the spindle pole
      associated protein NuMA. FAA-treated cells developed micronuclei which were
      predominantly CREST-positive, suggesting chromosomal instability. The Golgi
      complex was rapidly disrupted by FAA, without evident microtubules/tubulin
      alterations, and a sustained activation of the extracellular signal-regulated
      protein kinase (ERK) was also observed. Primary skin fibroblasts derived from HT1
      patients, not exogenously treated with FAA, showed similar mitotic-derived
      alterations and ERK activation. Biochemical data suggest that FAA causes ERK
      activation through a thiol-regulated and tyrosine kinase-dependent, but growth
      factor receptor- and protein kinase C-independent pathway. Pre-treatment with the
      MEK inhibitor PD98059 and the Ras farnesylation inhibitor B581 decreased the
      formation of CREST-positive micronuclei by approximately 75%, confirming the
      partial contribution of the Ras/ERK effector pathway to the induction of
      chromosomal instability by FAA. Replenishment of intracellular glutathione (GSH)
      with GSH monoethylester abolished ERK activation and reduced the chromosomal
      instability induced by FAA by 80%. Together these results confirm and extend the
      previously reported genetic instability occurring in cells from HT1 patients and
      allow us to speculate that this tumorigenic-related phenomenon may rely on the
      biochemical/cellular effects of FAA as a thiol-reacting and organelle/mitotic
      spindle-disturbing agent.

PMID- 11532984
TI  - Molecular scanning of the human sorbin and SH3-domain-containing-1 (SORBS1) gene:
      positive association of the T228A polymorphism with obesity and type 2 diabetes.
AB  - In the mouse, the SH3P12 or the c-Cbl-associated protein (CAP) has been shown as
      an important signaling molecule in insulin-stimulated glucose uptake. The human
      homolog for the sorbin and SH3-domain-containing-1 gene, termed SORBS1, might
      play a role in human disorders with insulin resistance. To explore the genetic
      role of SORBS1 in human obesity and type 2 diabetes, we investigated the
      nucleotide polymorphisms in the SORBS1 gene with molecular scanning. After
      scanning for a total of 13,136 bp in each of 40 chromosomes, we have identified
      14 single nucleotide polymorphisms (SNPs) in the human SORBS1 gene. Among them,
      two SNPs affected amino acid coding (R74W and T228A), four occurred within exons
      but did not affect amino acid coding, and the remaining eight occurred within
      introns, which were located outside of the consensus region of the splicing
      mechanism. Further studies in 202 non-obese, 113 obese and 455 subjects with type
      2 diabetes revealed that the A-allele of the T228A polymorphism in exon 7 exerted
      a protective role for both obesity [relative risk 0.466; 95% confidence interval
      (95% CI) 0.265-0.821] and diabetes (relative risk 0.668; 95% CI 0.472-0.945).
      Neither allele of the R74W polymorphism was associated with either obesity or
      diabetes. In conclusion, our results suggest that the A228 allele of the T228A
      polymorphism of the SORBS1 gene is a protective factor for both obesity and
      diabetes, and also imply that the SORBS1 gene plays an important role in the
      pathogenesis of human disorders with insulin resistance.

PMID- 11532985
TI  - The sarcolemmal proteins dysferlin and caveolin-3 interact in skeletal muscle.
AB  - Dysferlin is a surface membrane protein in skeletal muscle whose deficiency
      causes distal and proximal, recessively inherited, forms of muscular dystrophy
      designated Miyoshi myopathy (MM) and limb girdle muscular dystrophy type 2B
      (LGMD2B), respectively. The function of dysferlin is not defined. Caveolin-3 is
      another skeletal muscle membrane protein which is important in the formation of
      caveolae and whose mutations cause dominantly inherited limb girdle muscular
      dystrophy type 1C (LGMD1C). We report that dysferlin co-immunoprecipitates with
      caveolin-3 from biopsied normal human skeletal muscles. We also describe abnormal
      localization of dysferlin in muscles from patients with LGMD1C including novel
      missense mutation (T64P) in the human caveolin-3 gene (CAV3). The
      immunoprecipitation data are consistent with the parallel observation that
      dysferlin immunostaining is not normal in LGMD1C muscles. Amino acid sequence
      analysis of the dysferlin protein reveals seven sites that correspond to caveolin
      3 scaffold-binding motifs, and one site that is a potential target to bind the WW
      domain of the caveolin-3 protein. This is the first description of a possible
      dysferlin interacting protein; it suggests the hypothesis that one function of
      dysferlin may be to interact with caveolin-3 to subserve signaling functions of
      caveolae.

PMID- 11532986
TI  - The mutational spectrum of human malignant autosomal recessive osteopetrosis.
AB  - Human malignant infantile osteopetrosis (arOP; MIM 259700) is a genetically
      heterogeneous autosomal recessive disorder of bone metabolism, which, if
      untreated, has a fatal outcome. Our group, as well as others, have recently
      identified mutations in the ATP6i (TCIRG1) gene, encoding the a3 subunit of the
      vacuolar proton pump, which mediates the acidification of the bone/osteoclast
      interface, are responsible for a subset of this condition. By sequencing the
      ATP6i gene in arOP patients from 44 unrelated families with a worldwide
      distribution we have now established that ATP6i mutations are responsible for
      approximately 50% of patients affected by this disease. The vast majority of
      these mutations (40 out of 42 alleles, including seven deletions, two insertions,
      10 nonsense substitutions and 21 mutations in splice sites) are predicted to
      cause severe abnormalities in the protein product and are likely to represent
      null alleles. In addition, we have also analysed nine unrelated arOP patients
      from Costa Rica, where this disease is apparently much more frequent than
      elsewhere. All nine Costa Rican patients bore either or both of two missense
      mutations (G405R and R444L) in amino acid residues which are evolutionarily
      conserved from yeast to humans. The identification of ATP6i gene mutations in two
      families allowed us for the first time to perform prenatal diagnosis: both
      fetuses were predicted not to be affected and two healthy babies were born. This
      study contributes to the determination of genetic heterogeneity of arOP and
      allows further delineation of the other genetic defects causing this severe
      condition.

PMID- 11532987
TI  - Mutations in the X-linked filamin 1 gene cause periventricular nodular
      heterotopia in males as well as in females.
AB  - Periventricular heterotopia (PH) is a human neuronal migration disorder in which
      many neurons destined for the cerebral cortex fail to migrate. Previous analysis
      showed heterozygous mutations in the X-linked gene filamin 1 (FLN1), but examined
      only the first six (of 48) coding exons of the gene and hence did not assess the
      incidence and functional consequences of FLN1 mutations. Here we perform single
      strand conformation polymorphism (SSCP) analysis of FLN1 throughout its entire
      coding region in six PH pedigrees, 31 sporadic female PH patients and 24 sporadic
      male PH patients. We detected FLN1 mutations by SSCP in 83% of PH pedigrees and
      19% of sporadic females with PH. Moreover, no PH females (0/7 tested) with
      atypical radiographic features showed FLN1 mutations, suggesting that other genes
      may cause atypical PH. Surprisingly, 2/24 males analyzed with PH (9%) also
      carried FLN1 mutations. Whereas FLN1 mutations in PH pedigrees caused severe
      predicted loss of FLN1 protein function, both male FLN1 mutations were consistent
      with partial loss of function of the protein. Moreover, sporadic female FLN1
      mutations associated with PH appear to cause either severe or partial loss of
      function. Neither male could be shown to be mosaic for the FLN1 mutation in
      peripheral blood lymphocytes, suggesting that some neurons in the intact cortex
      of PH males may be mutant for FLN1 but migrate adequately. These results
      demonstrate the sensitivity and specificity of DNA testing for FLN1 mutations and
      have important functional implications for models of FLN1 protein function in
      neuronal migration.

PMID- 11532988
TI  - Quantitative effects on gene silencing by allelic variation at a tetranucleotide
      microsatellite.
AB  - Microsatellites are common repeated sequences, which are useful as genetic
      markers and lack any clearly established function. In a previous study we
      suggested that an intronic polymorphic TCAT repeat in the tyrosine hydroxylase
      (TH) gene, the microsatellite HUMTH01, may regulate transcription. The TH gene
      encodes the rate-limiting enzyme in the synthesis of catecholamines, and the
      microsatellite HUMTH01 has been used in genetic studies of neuropsychiatric and
      cardiovascular diseases, in which disturbances of catecholaminergic
      neurotransmission have been implicated. HUMTH01 alleles associated with these
      diseases act as transcriptional enhancers when linked to a minimal promoter and
      are recognized by specific nuclear factors. Here we show that allelic variations
      of HUMTH01 commonly found in humans have a quantitative silencing effect on TH
      gene expression. Two specific proteins, ZNF191, a zinc finger protein, and HBP1,
      an HMG box transcription factor, which bind the TCAT motif, were then cloned.
      Finally, allelic variations of HUMTH01 correlate with quantitative and
      qualitative changes in the binding by ZNF191. Thus, this repeated sequence may
      contribute to the control of expression of quantitative genetic traits. As the
      HUMTH01 core motif is ubiquitous in the genome, this phenomenon may be relevant
      to the quantitative expression of many genes in addition to TH.

PMID- 11532989
TI  - Insights into psoriasis and other inflammatory diseases from large-scale gene
      expression studies.
AB  - Approximately 2% of the Caucasian population is affected by psoriasis (PS); a
      chronic inflammatory skin disease triggered by both genetic and environmental
      risk factors. In addition to a major contribution from the HLA class I region, PS
      susceptibility loci have been mapped to a number of regions including 1q21, 3q21,
      4qter, 14q31-q32, 17q24-q25, 19p13.3 and 20p. Some of these overlap with loci
      implicated in other autoimmune/inflammatory diseases. Global gene expression
      studies are beginning to provide insights into the etiology of these and other
      complex diseases. We used Affymetrix oligonucleotide arrays comprising
      approximately 12 000 known genes to initiate a more comprehensive analysis of the
      transcriptional changes that occur in involved and uninvolved skin of 15
      psoriatic patients versus six normal controls. Expression levels of the
      transcripts detected on the arrays were first used to determine the relationship
      of samples to each other using hierarchical clustering. This analysis clearly
      differentiated involved psoriatic skin from uninvolved and normal skin. Clusters
      of differentially expressed genes with similar expression patterns in the same
      samples were then identified. Six out of 32 clusters contained a total of 177
      transcripts that were differentially expressed in involved psoriatic skin versus
      normal skin. These differences were independent of the gender, age, skin site and
      HLA class I status of the patient. Ten of the 177 genes were also differentially
      expressed in uninvolved skin, and several mapped to regions previously shown to
      harbor psoriasis susceptibility loci.

PMID- 11532990
TI  - The huntingtin interacting protein HIP1 is a clathrin and alpha-adaptin-binding
      protein involved in receptor-mediated endocytosis.
AB  - The huntingtin interacting protein (HIP1) is enriched in membrane-containing cell
      fractions and has been implicated in vesicle trafficking. It is a multidomain
      protein containing an N-terminal ENTH domain, a central coiled-coil forming
      region and a C-terminal actin-binding domain. In the present study we have
      identified three HIP1 associated proteins, clathrin heavy chain and alpha-adaptin
      A and C. In vitro binding studies revealed that the central coiled-coil domain is
      required for the interaction of HIP1 with clathrin, whereas DPF-like motifs
      located upstream to this domain are important for the binding of HIP1 to the C
      terminal 'appendage' domain of alpha-adaptin A and C. Expression of full length
      HIP1 in mammalian cells resulted in a punctate cytoplasmic immunostaining
      characteristic of clathrin-coated vesicles. In contrast, when a truncated HIP1
      protein containing both the DPF-like motifs and the coiled-coil domain was
      overexpressed, large perinuclear vesicle-like structures containing HIP1,
      huntingtin, clathrin and endocytosed transferrin were observed, indicating that
      HIP1 is an endocytic protein, the structural integrity of which is crucial for
      maintenance of normal vesicle size in vivo.

PMID- 11532991
TI  - Pathological and genetic analysis of the degenerating muscle (dmu) mouse: a new
      allele of Scn8a.
AB  - Here, we describe a novel spontaneous autosomal recessive mutation in the mouse
      that is characterized by skeletal and cardiac muscle degeneration. We have named
      this mutant degenerating muscle (dmu). At birth, mutant mice are
      indistinguishable from their normal littermates. Thereafter, the disease
      progresses rapidly and a phenotype is first observed at approximately 11 days
      after birth; the dmu mice are weak and have great difficulty in moving. The
      principal cause of the lack of mobility is muscle atrophy and wasting in the
      hindquarters. Affected mice die at or around the time of weaning of unknown
      causes. Histopathological observations and ultrastructural analysis revealed
      muscle degeneration in both skeletal and cardiac muscle, but no abnormalities in
      sciatic nerves. Using linkage analysis, we have mapped the dmu locus to the
      distal portion of mouse chromosome 15 in a region syntenic to human chromosome
      12q13. Interestingly, scapuloperoneal muscular dystrophy (SPMD) in humans has
      been linked to this region. SPMD patients with associated cardiomyopathy have
      also been described in the past. Initial analysis of candidate genes on mouse
      chromosome 15 reveal that although intact transcripts for Scn8a, the gene
      encoding the sodium channel 8a subunit, are present in dmu mice, their levels are
      dramatically reduced. Furthermore, genetic complementation crosses between dmu
      and med (mutation in Scn8a) mice revealed that they are allelic. Our results
      suggest that at least a portion of the dmu phenotype is caused by a down
      regulation of Scn8a, making dmu a new allele of Scn8a.

PMID- 11532993
TI  - alpha-Synuclein gene haplotypes are associated with Parkinson's disease.
AB  - We report haplotype analysis of the alpha-synuclein gene in Parkinson's disease
      (PD), extending earlier reports of an association with a polymorphism within the
      gene promoter. This analysis showed significant differences in haplotypes between
      PD cases and controls. Our analyses demonstrate that genetic variability in the
      alpha-synuclein gene is a risk factor for the development of PD. These genetic
      findings are analogous to the tau haplotype over-represented in progressive
      supranuclear palsy and further extend the similarity in the etiologies and
      pathogeneses of the synucleinopathies and tauopathies.

PMID- 11532992
TI  - Polyglutamine expansions cause decreased CRE-mediated transcription and early
      gene expression changes prior to cell death in an inducible cell model of
      Huntington's disease.
AB  - Huntington's disease (HD) is one of 10 known diseases caused by a (CAG)(n)
      trinucleotide repeat expansion that is translated into an abnormally long
      polyglutamine tract. We have developed stable inducible neuronal (PC12) cell
      lines that express huntingtin exon 1 with varying CAG repeat lengths under
      doxycycline (dox) control. The expression of expanded repeats is associated with
      aggregate formation, caspase-dependent cell death and decreased neurite
      outgrowth. Post-mitotic cells expressing mutant alleles were more prone to cell
      death compared with identical cycling cells. To determine early metabolic changes
      induced by this mutation in cell models, we studied changes in gene expression
      after 18 h dox induction, using Affymetrix arrays, cDNA filters and adapter
      tagged competitive PCR (ATAC-PCR). At this time point there were low rates of
      inclusion formation, no evidence of mitochondrial compromise and no excess cell
      death in the lines expressing expanded compared with wild-type repeats. The
      expression profiles suggest novel targets for the HD mutation and were compatible
      with impaired cAMP response element (CRE)-mediated transcription, which we
      confirmed using CRE-luciferase reporter assays. Reduced CRE-mediated
      transcription may contribute to the loss of neurite outgrowth and cell death in
      polyglutamine diseases, as these phenotypes were partially rescued by treating
      cells with cAMP or forskolin.

PMID- 11532994
TI  - Domain homologues of dopamine beta-hydroxylase and ferric reductase: roles for
      iron metabolism in neurodegenerative disorders?
AB  - One of the defining characteristics of neurodegenerative diseases, including
      Parkinson's, Alzheimer's and Huntington's diseases, is abnormal accumulations of
      iron, specifically in affected areas. Following injection of iron in rat brains,
      a relatively selective lesion of dopamine neurons, similar to parkinsonism,
      occurs. These observations indicate that Fe(II)-mediated generation of free
      radical species, by the Fenton reaction, might contribute to the pathoetiology of
      these diseases. Iron is known to possess multiple roles in the biosynthesis of
      catecholamines in dopaminergic neurons. These include, as Fe(II), facilitating
      the production of dopamine from phenylalanine by tyrosine hydroxylase, and as
      heme, assisting the recycling of ascorbate by cytochrome b-561 required for the
      generation of norepinephrine from dopamine by dopamine beta-hydroxylase. In this
      study, it is demonstrated that a human and mouse gene product, stromal cell
      derived receptor 2, is a homologue of cytochrome b-561 and duodenal cytochrome b,
      and is thus predicted to be active as a ferric reductase. Moreover, this protein
      also contains a domain homologous to the N-terminal regulatory region of dopamine
      beta-hydroxylase. These findings from sequence analysis lead to a prediction that
      stromal cell-derived receptor 2 is a catecholamine-regulated ferric reductase
      active in the brain. Dysfunction of cytochrome b-561 or stromal cell-derived
      receptor 2, therefore, might predispose individuals to abnormal accumulation of
      Fe(III) and/or generation of cytotoxic free radicals as a consequence of a rapid
      cycling between Fe(III) and Fe(II). The hypothesis that aberrant ferric reductase
      activities are involved in the progression of neurodegenerative diseases should
      open up new avenues of research, and possibly therapy, for these devastating
      diseases.

PMID- 11532995
TI  - Identification of an endogenous RNA transcribed from the antisense strand of the
      HFE gene.
AB  - Hereditary haemochromatosis is an autosomal recessive disease which results in
      iron overload, and it is the most frequently inherited disorder in Caucasian
      populations. The gene involved (HFE) has recently been identified, and it encodes
      an MHC class I-like molecule. A 2.7 kb cDNA has been isolated, whereas the HFE
      gene expression is characterized by an almost ubiquitous mRNA of 4.1 kb in size.
      The difference between this transcript and the isolated cDNA has not yet been
      explained. Thus, the 5' end of the HFE gene is still undefined and very little is
      known about the regulation of its expression. By searching this end, we isolated
      an antisense transcript originating from the same gene locus. Further
      investigations (rapid amplification of cDNA ends, RT-PCR experiments and dbEST
      screening) indicated that this RNA spans exon 1, exon 2, part of intron 1 of the
      HFE gene and approximately 1 kb upstream of it. This HFE antisense transcript is
      polyadenylated but displays no open reading frame. A ribonuclease A protection
      assay definitively demonstrated the biological existence of the HFE antisense
      RNA, which appears to be expressed in all of the tissues and cell lines tested.
      Furthermore, in vitro coupled transcription-translation experiments revealed that
      the HFE expression is decreased by this antisense RNA, indicating that it may
      play a critical role in the regulation of the HFE gene expression.

PMID- 11532996
TI  - Liposome-encapsulated aminoglycosides in pre-clinical and clinical studies.
AB  - Liposome-encapsulated amikacin has recently entered clinical trials. The
      rationale for liposome encapsulation of aminoglycosides is the possibility to
      increase the therapeutic index of this class of antibiotics by increasing
      aminoglycoside concentrations at the site of infection and/or by reducing the
      toxicity of these drugs. Three approaches can be distinguished: the use of
      liposomes as a depot formulation for local drug administration; targeting of
      (relatively) short circulating conventional liposomes to the cells of the
      mononuclear phagocyte system (MPS) for treating intracellular bacterial
      infections; and targeting of long-circulating liposomes to infectious foci
      localized outside the MPS. This review discusses the pre-clinical and clinical
      data in connection with recent developments in liposome technology.

PMID- 11532997
TI  - Antifungal resistance and over-the-counter availability in the UK: a current
      perspective.

PMID- 11532998
TI  - Antiretroviral drug concentrations in semen of HIV-infected men: differential
      penetration of indinavir, ritonavir and saquinavir.
AB  - Variable drug penetration of antiretroviral drugs into the genital tract may
      contribute to the differential evolution of HIV and the emergence of drug
      resistance. This, in turn, may have an impact on the sexual transmission of
      resistant HIV in patients treated with antiretroviral drugs. We have measured
      concentrations of the HIV-1 protease inhibitors indinavir, ritonavir and
      saquinavir in the blood plasma (BP) and seminal plasma (SP) of 23 HIV-1-positive
      men. Forty-five time-matched blood and semen samples were obtained. SP
      concentrations of indinavir exceeded the EC95 of indinavir, corrected for protein
      binding, of 42 ng/mL at all time intervals. In contrast, the median ritonavir and
      saquinavir SP concentrations were below the relevant EC95 at all times post drug
      ingestion. The median SP:BP concentration ratios for indinavir were 0.6, 0.8 and
      1.4, respectively, at 0-2, 2-6 and 6-8 h post-drug ingestion. In contrast, the
      median SP:BP concentration ratios at 0-3, 3-9 and 9-12 h post-drug ingestion were
      <0.02, <0.04 and <0.04, respectively, for both ritonavir and saquinavir. These
      differences justify further study of HIV-1 evolution and development of
      resistance in the genital tract of men taking these anti-HIV drugs.

PMID- 11532999
TI  - Incidence and risk factors for the development of indinavir-associated renal
      complications.
AB  - OBJECTIVES: To describe the incidence and risk factors for the development of
      indinavir-associated renal complications (IRC), and subsequent clinical outcome.
      PATIENTS AND METHODS: This was a retrospective cohort study based on two large
      HIV centres in London. Eligible patients received indinavir for at least 1 week
      between 1 December 1995 and 28 February 1999. Development of IRC was ascertained
      by case-note review. Multivariate logistic regression and Cox Proportional
      Hazard's model analysis were used to determine independent risk factors for the
      development of IRC. RESULTS: 781 patients were eligible. Median CD4 count and
      viral load at indinavir initiation were 117 x 10(6) cells/L and 47 332 copies/mL,
      respectively. Median indinavir exposure was 53 weeks (IQR: 20-83). Many patients
      received other potentially nephrotoxic drugs during indinavir treatment: co
      trimoxazole (46%), aciclovir (33%) or both (20%). Overall IRC incidence was 7.3%
      (6.7 per 100 person-years indinavir exposure). Cases presented with loin pain
      (58%), renal colic (42%) or dysuria (19%). Identified precipitating events (26%)
      included fluid depletion or altered indinavir regimen. In the majority of cases
      indinavir therapy was continued and there was no progressive rise in creatinine
      levels. In the multivariate analysis, for indinavir treatment >74 weeks there was
      a reduced risk of developing IRC (OR = 0.23, 95% CI 0.09-0.57, P = 0.001).
      Concomitant aciclovir increased the IRC risk (OR = 1.99, 95% CI 1.14-3.51, P =
      0.016). Factors not associated with outcome were age, gender, ethnicity, baseline
      CD4 count and viral load, concomitant co-trimoxazole, or use of specific
      antiretrovirals. CONCLUSION: An overall IRC incidence of 7.3% was identified.
      Concomitant aciclovir doubled the risk of IRC and we therefore recommend careful
      monitoring when prescribing aciclovir with indinavir. A precipitating event was
      identified in 26% of IRC cases, many of which could have been avoided.

PMID- 11533000
TI  - Epigallocatechin gallate synergy with ampicillin/sulbactam against 28 clinical
      isolates of methicillin-resistant Staphylococcus aureus.
AB  - Compared with ampicillin, oxacillin, cefmetazole and imipenem, the combination of
      ampicillin and sulbactam at a constant ratio of 2:1 showed the greatest effect
      against 28 clinical isolates of methicillin-resistant Staphylococcus aureus
      (MRSA), but MICs of ampicillin/sulbactam were still above the resistance
      breakpoint. When ampicillin/sulbactam was further combined with epigallocatechin
      gallate (EGCg, a main constituent of tea catechins), the MIC90 of ampicillin/
      sulbactam was reduced to 4 mg/L, the susceptibility breakpoint. The fractional
      inhibitory concentration indices were between 0.19 and 0.56 in combination with
      6.25 and 25 mg/L EGCg, respectively, indicating that ampicillin/sulbactam and
      EGCg combination may be effective against MRSA infections.

PMID- 11533001
TI  - Single- and multi-step resistance selection study of gemifloxacin compared with
      trovafloxacin, ciprofloxacin, gatifloxacin and moxifloxacin in Streptococcus
      pneumoniae.
AB  - The ability of sequential subcultures in subinhibitory concentrations of
      gemifloxacin, trovafloxacin, ciprofloxacin, gatifloxacin and moxifloxacin to
      select resistant mutants was studied in 16 pneumococci [eight with ciprofloxacin
      MICs (mg/L) 0.25-1; four with 8-16; four with 16-32]. Subculturing was done 50
      times, or until mutants with elevated MICs (> or = 4 x) to the selecting drug
      emerged. Subculturing in gemifloxacin selected six resistant mutants
      (gemifloxacin MICs 2 mg/L); trovafloxacin selected nine (trovafloxacin MICs 2-4
      mg/L); ciprofloxacin selected 11 (ciprofloxacin MICs 8-128 mg/L); gatifloxacin
      selected 13; and moxifloxacin selected 12 (gatifloxacin or moxifloxacin MICs 2-16
      mg/L). DNA sequencing showed that most mutants had mutations in ParC at Ser-79 or
      Asp-83 and in GyrA at Ser-81 or Glu-85; some mutants also had mutations in ParE
      or GyrB. Some new mutations were found in ParE or GyrB that have not yet been
      reported; GyrB mutation might be associated with moxifloxacin resistance. Both
      DNA gyrase and topoisomerase IV were thought to be the target of gemifloxacin;
      gemifloxacin also selected mutants with single modifications in gyrA, parC or
      parE alone among derived mutants by repeated exposure to subinhibitory
      concentrations of fluoroquinolones. In the presence of reserpine, most mutants
      had lower MICs of ciprofloxacin and gemifloxacin (4-32 x), and gatifloxacin (4-8
      x), suggesting an efflux mechanism; none had lower trovafloxacin and moxifloxacin
      MICs. All quinolones tested selected for resistance; judicious use and proper
      dosing will be necessary to avoid resistance selection of newer broad-spectrum
      fluoroquinolones.

PMID- 11533002
TI  - Selection of high-level oxacillin resistance in heteroresistant Staphylococcus
      aureus by fluoroquinolone exposure.
AB  - To study the effect of fluoroquinolone exposure on the expression of mec(A)
      encoded oxacillin resistance, population analysis profiling was performed on four
      strains of fluoroquinolone-susceptible, mec(A)-positive, heteroresistant
      Staphylococcus aureus. Growth in the presence of 0.5 x MIC of a fluoroquinolone
      resulted in >10-fold increase in the proportion of the population that grew on
      agar containing oxacillin 128 mg/L. Ciprofloxacin exhibited a greater effect than
      moxifloxacin, levofloxacin and gatifloxacin (average 3400-, 220-, 170- and 49
      fold increase in oxacillin-resistant colonies versus the control, respectively).
      The increase was directly proportional to the fluoroquinolone concentration and
      could be detected as early as 8 h after exposure to the fluoroquinolone. At 8 h,
      the absolute number of colonies that grew on oxacillin 128 mg/L was similar
      whether or not the isolate was exposed to the fluoroquinolone, but the total cfu
      on non-selective media decreased. The resultant oxacillin-resistant colonies also
      showed a 1.5- to 3-fold increase in fluoroquinolone MIC. No oxacillin resistance
      was observed on two similarly treated fluoroquinolone-susceptible, mec(A)
      negative strains. It appears that fluoroquinolones influence oxacillin resistance
      by selective inhibition or killing of the more susceptible subpopulations in
      heteroresistant S. aureus. The surviving populations are more resistant to both
      oxacillin and fluoroquinolone. The mechanisms of resistance to the two agents may
      be unrelated but tend to be associated. This could explain in part the observed
      increases in fluoroquinolone-resistant MRSA.

PMID- 11533003
TI  - CMY-2-producing Salmonella enterica, Klebsiella pneumoniae, Klebsiella oxytoca,
      Proteus mirabilis and Escherichia coli strains isolated in Spain (October 1999
      December 2000).
AB  - CMY-2 plasmid-mediated AmpC beta-lactamase (CMY-2) was detected in 21 isolates
      from two hospitals located in different geographical regions of Spain between
      October 1999 and December 2000. The isolates comprised two Salmonella enterica
      serovars (Mikawasima and Montevideo), 16 Escherichia coli, one Klebsiella
      pneumoniae, one Klebsiella oxytoca and one Proteus mirabilis. In addition to the
      expected resistance to beta-lactams, including extended-spectrum cephalosporins
      and cefoxitin, all isolates showed a broad spectrum of associated resistance. All
      were resistant to sulfamethoxazole, chloramphenicol, tetracycline and
      streptomycin, and all but two were also resistant to gentamicin. Five isolates
      were studied in detail and all transferred CMY-2 and other resistance
      determinants by conjugation. Genomic DNA restriction pattern analysis of the E.
      coli isolates excluded the dissemination of a single clone. To the best of our
      knowledge this is the first time that CMY-2 has been detected in P. mirabilis, K.
      oxytoca and S. enterica serovars Mikawasima and Montevideo. It is also the first
      time that CMY-2 has been described in Spain.

PMID- 11533005
TI  - Effects of amoxicillin on the expression of cytokines during experimental acute
      otitis media caused by non-typeable Haemophilus influenzae.
AB  - Antibiotics are frequently prescribed when a diagnosis of acute otitis media
      (AOM) is made in childhood, but the effects of antibiotics on host-parasite
      interactions in the middle ear are not well defined. A rat model and PCR
      techniques were used to explore host responses during amoxicillin treatment of
      AOM caused by non-typeable Haemophilus influenzae (NTHi). The 5 day course of
      amoxicillin initiated at the otomicroscopic peak of the infection eradicated the
      bacteria and induced significant changes in the expression of cytokines.
      Interleukin (IL)-6, tumour necrosis factor-alpha and IL-10 were upregulated by
      the treatment, and the downregulation was slower than during the natural course.
      Amoxicillin inhibited the upregulation of transforming growth factor-beta,
      whereas IL-1alpha expression remained unaffected by the treatment. By comparing
      inflammatory host responses during treated and untreated NTHi AOM, new targets
      for modification of the course, or more specified and individualized treatments,
      may evolve.

PMID- 11533004
TI  - Characterization of paired mucoid/non-mucoid Pseudomonas aeruginosa isolates from
      Danish cystic fibrosis patients: antibiotic resistance, beta-lactamase activity
      and RiboPrinting.
AB  - The purpose of this study was to characterize 42 paired mucoid and non-mucoid
      Danish cystic fibrosis (CF) Pseudomonas aeruginosa isolates collected in 1997, by
      RiboPrinting, antibiotic susceptibility and beta-lactamase activity. Eight P.
      aeruginosa isolates collected before 1991 were included for comparison. Eighteen
      of the 42 paired mucoid and non-mucoid isolates showed the same ribotype; the
      remaining 24 belonged to different ribogroups. Mucoid isolates showed higher
      susceptibility to antibiotics and lower beta-lactamase activity compared with non
      mucoid isolates. Significant differences (P < or = 0.01) between mucoid and non
      mucoid isolates were found for the meropenem and colistin MICs for the isolates
      with the same ribotype, and for the MICs of ceftazidime, piperacillin, aztreonam,
      meropenem, tobramycin, ciprofloxacin and in the basal levels of beta-lactamase
      for the paired isolates belonging to different ribogroups. A dominant ribotype 73
      S2 with hyperinducible beta-lactamase production and significantly higher MICs of
      piperacillin, meropenem and tobramycin compared with the other major ribotypes
      (73-S1, 207-S3 and 227-S8) was present among the 84 CF isolates. The isolates
      collected before 1991 had an antibiotic susceptibility pattern similar to the
      1997 isolates. Despite prolonged and intensive antibiotic treatment, susceptible
      mucoid isolates were isolated from the CF sputum, possibly because these bacteria
      are protected from the selective pressure of antibiotics by the resistant non
      mucoid isolates co-existing in the biofilm in the lungs of CF patients.

PMID- 11533006
TI  - In vitro activity of telithromycin, a new ketolide, against Chlamydia pneumoniae.
AB  - The in vitro activity of telithromycin, a new ketolide, was compared with those
      of roxithromycin, azithromycin, clarithromycin and erythromycin A against 20
      strains of Chlamydia pneumoniae. The MICs and minimal chlamydiacidal
      concentrations of telithromycin for the 20 C. pneumoniae strains both ranged
      between 0.031 and 0.25 mg/L. Telithromycin was twice as active as roxithromycin,
      azithromycin and erythromycin A, but less active than clarithromycin. These
      results appear to indicate that telithromycin is an effective antibiotic that
      should play some role in the treatment of respiratory tract infections caused by
      C. pneumoniae.

PMID- 11533007
TI  - In vitro activity of a novel ketolide ABT-773 against invasive strains of
      Streptococcus pneumoniae.
AB  - New ketolides such as ABT-773 are a promising group of antibiotics in an era of
      increasing antibiotic resistance. We tested 704 invasive strains of Streptococcus
      pneumoniae collected from 1990 to 1998. Overall resistance was 8.3, 4.6, 4.5 and
      3.6% for penicillin, cefuroxime, erythromycin and clarithromycin, respectively.
      By using a recommended breakpoint for susceptibility of <0.5 mg/L, no strains
      showed reduced susceptibility to ABT-773. ABT-773 was very active against all
      penicillin-resistant strains (MIC > 2 mg/L, with a mean geometric mean <0.06
      mg/L), and against all 33 erythromycin-resistant strains, irrespective of the
      mode of resistance [mef- or erm(B)-mediated]. ABT-773 is a very active and
      promising agent against invasive strains of S. pneumoniae, including
      multiresistant strains.

PMID- 11533008
TI  - In vitro selection of resistance to clindamycin related to alterations in the
      attenuator of the erm(TR) gene of Streptococcus pyogenes UCN1 inducibly resistant
      to erythromycin.
AB  - A clinical isolate of Streptococcus pyogenes UCN1 intermediate to erythromycin
      (MIC 1 mg/L) and susceptible to clindamycin (MIC 0.03 mg/L) harboured an
      inducible erm(TR) gene encoding a ribosomal methylase. We have selected in vitro,
      in the presence of concentrations of clindamycin ranging from 0.12 to 1 mg/L, one
      step mutants that are highly resistant to this antibiotic (MIC 64 mg/L) at a
      frequency of 10(-7). By contrast, in an erythromycin-susceptible strain of S.
      pyogenes UCN5, mutants could be selected only by a low concentration of
      clindamycin (0.12 mg/L) at a frequency of 10(-9). Clindamycin resistance in four
      of six S. pyogenes UCN1 mutants was associated with deletions of 163 and 6 bp, as
      well as a tandem duplication of 101 bp in the regulatory sequence of the erm(TR)
      gene. The role of these structural alterations in clindamycin resistance was
      demonstrated by cloning the erm(TR) gene from the wild-type and mutant strains in
      Escherichia coli DB10, a mutant susceptible to macrolides. Clindamycin resistance
      was expressed only when the erm(TR) gene was preceded by an altered attenuator.
      Mutations could lead to the formation of mRNA secondary structures accounting for
      the accessibility of the ribosome-binding site and the initiation codon of the
      ErmTR methylase to the ribosomes, and subsequently for the translation of the
      erm(TR) transcripts. The easy selection in one step of mutants resistant to high
      levels of clindamycin by concentrations of this antibiotic ranging from four to
      40 times the MIC leads us to recommend caution in the use of clindamycin therapy
      in group A Streptococcus infections.

PMID- 11533009
TI  - Effect of serum from different patient populations on the serum bactericidal
      test.
AB  - We evaluated the effect of serum from normal and uraemic volunteers, neutropenic
      patients and burn patients on the serum bactericidal test. Serum samples were
      spiked with ceftazidime to mimic in vivo peak (75 mg/L) and trough (5 mg/L)
      concentrations. Serum inhibitory and bactericidal titres (SIT and SBT) were
      performed in triplicate using Escherichia coli ATCC 25922 and Pseudomonas
      aeruginosa ATCC 27853. For E. coli, the trough SIT and SBT were significantly
      higher in serum from burn patients compared with normal volunteers (P < or =
      0.024). The trough SIT was significantly higher in serum from burn patients
      compared with neutropenic patients (P = 0.022) and in uraemic patients compared
      with normal volunteers (P = 0.04). No significant differences between subject
      populations were found for P. aeruginosa.

PMID- 11533010
TI  - Quinolone resistance in potentially pathogenic and non-pathogenic Escherichia
      coli strains isolated from healthy ruminants.
AB  - Quinolone resistance was studied in potentially pathogenic and non-pathogenic
      Escherichia coli strains from healthy ruminants. In cattle, 5.9% of the strains
      were resistant to nalidixic acid and 4.9% were resistant to enrofloxacin and
      ciprofloxacin, whereas in sheep and goats only 0.5% and 1.4%, respectively, of
      the strains were resistant to nalidixic acid and none to fluoroquinolones. Most
      of the strains resistant to quinolones were non-pathogenic strains isolated from
      cattle. However, the results of this study do not show that the potentially
      pathogenic E. coli strains isolated from healthy ruminants are more susceptible
      to quinolones than the non-pathogenic E. coli strains.

PMID- 11533011
TI  - Efficacy of azithromycin, clarithromycin and beta-lactam agents against
      experimentally induced bronchopneumonia caused by Haemophilus influenzae in mice.
AB  - Azithromycin is an azalide with potent activity against Haemophilus influenzae
      including ampicillin-resistant strains. We evaluated the efficacy of
      azithromycin, clarithromycin and three beta -lactams when used for 1 day only and
      for 3 days for the treatment of a murine model of bronchopneumonia, using three
      strains of H. influenzae, two of which were ampicillin resistant. MICs of
      azithromycin (1-2 mg/L) and clarithromycin (4-8 mg/L) were similar for the three
      strains. The MICs of cefdinir and cefcapene for beta-lactamase-negative
      ampicillin-resistant (BLNAR) H. influenzae were 32 times higher than those for
      beta-lactamase-positive ampicillin-resistant and ampicillin-susceptible strains.
      The viable counts in the infected tissues of azithromycin-treated mice with
      bronchopneumonia caused by the susceptible strain TUM8, beta-lactamase-positive
      strain TUH36 and BLNAR strain TUH267 were less than the counts obtained with the
      other antibiotics used, irrespective of MIC. At a dose of 50 mg/kg, the area
      under the concentration curve and the half-life of azithromycin in the lungs were
      respectively three times higher and six times longer than those of
      clarithromycin. Our results indicate that azithromycin may be useful for both
      ampicillin-susceptible and ampicillin-resistant bronchopneumonial infections
      caused by H. influenzae.

PMID- 11533012
TI  - Airways delivery of rifampicin microparticles for the treatment of tuberculosis.
AB  - A Mycobacterium tuberculosis (H37Rv)-infected guinea pig model was used to screen
      for targeted delivery to the lungs by insufflation (with lactose excipient) or
      nebulization, of either rifampicin alone, rifampicin within poly(lactide-co
      glycolide) microspheres (R-PLGA) or polymer microparticles alone (PLGA). Animals
      treated with single and double doses of R-PLGA microspheres exhibited
      significantly reduced numbers of viable bacteria, inflammation and lung damage
      compared with lactose-, PLGA- or rifampicin-treated animals 28 days post
      infection (P < 0.05). Two doses of R-PLGA resulted in reduced splenic
      enlargement. These studies support the potential of R-PLGA delivered to the lung
      to treat pulmonary tuberculosis.

PMID- 11533013
TI  - Antibiotics and shared decision-making in primary care.
AB  - Antibiotics are often prescribed to patients with respiratory tract infections
      who are unlikely to benefit. Models of physician-patient interaction may help
      understanding of this problem and inform the design of communication skills
      interventions to enhance appropriate prescribing. The 'paternalistic model' of
      the consultation remains common in the setting of acute respiratory tract
      infections. However, the four assumptions that could support this model are not
      valid for most of these patients, because: best treatment is controversial;
      management is inconsistent; physicians are not in the best position to evaluate
      trade-offs between management options without understanding patients'
      perspectives; and many pressures (apart from patients' agendas) intrude into the
      consultation. One alternative is the 'informed model' of consulting, but this
      does not take society's interests into account. The 'shared decision-making
      model', however, provides a framework for addressing both clinicians' and
      patients' agendas, and could guide the development and evaluation of specific
      consultation strategies to promote more appropriate use of antibiotics in primary
      care.

PMID- 11533014
TI  - Antibiotic use and resistance of Streptococcus pneumoniae in The Netherlands
      during the period 1994-1999.
AB  - Antibiotic use in The Netherlands during the period 1994-1999 is described in
      relation to the resistance of routine isolates of Streptococcus pneumoniae. The
      average antibiotic use in the study period was 3.4 defined daily doses per 1000
      persons per day (DDD/1000/day) penicillins, 0.066 DDD/1000/day beta-lactams other
      than penicillins, 2.3 DDD/1000/day tetracyclines and 0.71 DDD/1000/day
      trimethoprim and sulphonamides, without apparent rise or decline. In contrast,
      the use of macrolides doubled from 0.51 DDD/1000/day in 1994 to 1.0 DDD/1000/day
      in 1997 and stayed at 1.07 DDD/1000/day in 1998 and 1999. In 1994 the first
      pneumococci isolated from patients showed 0.7% resistance to penicillin
      (intermediate plus full resistance), 2.5% to erythromycin, 4.2% to co-trimoxazole
      and 4.7% to tetracycline. In 1999 first isolates showed 1.5% resistance to
      penicillin, 3.8% to erythromycin, 4.4% to co-trimoxazole and 6.6% to
      tetracycline. The modest but significant rise in the resistance to erythromycin
      may have been caused by the increased use of macrolides in the years 1994-1997.
      The rise in resistance to penicillin seemed not to be related to increased beta
      lactam use.

PMID- 11533015
TI  - Intracellular penetration and bactericidal activity of the novel des-fluoro(6)
      quinolone, BMS-284756.

PMID- 11533016
TI  - Comparison of the in vitro activities of BMS-284756 and four fluoroquinolones
      against Streptococcus pneumoniae.

PMID- 11533017
TI  - In vitro susceptibility of the Borrelia burgdorferi sensu lato complex to ABT
      773, a novel ketolide.

PMID- 11533018
TI  - Antileishmanial activity of the violacein extracted from Chromobacterium
      violaceum.

PMID- 11533019
TI  - Melaleuca alternifolia (tea tree) oil gel (6%) for the treatment of recurrent
      herpes labialis.

PMID- 11533020
TI  - Susceptibility testing with linezolid by different methods, in relation to
      published 'general breakpoints'.

PMID- 11533021
TI  - Clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) with
      reduced susceptibility to teicoplanin in Northwest England.

PMID- 11533022
TI  - Antibiotic resistance in Campylobacter spp. isolated from human faeces (1980
      2000) and foods (1997-2000) in Northern Ireland: an update.

PMID- 11533023
TI  - Increased consumption of fluoroquinolones is not associated with resistance in
      Escherichia coli and Staphylococcus aureus in the community.

PMID- 11533025
TI  - Phosphorylation of the integrin alpha 4 cytoplasmic domain regulates paxillin
      binding.
AB  - alpha4 integrins are essential for embryogenesis, hematopoiesis, inflammation,
      and immune response possibly because alpha4 integrins have distinct signaling
      properties from other integrins. Specifically, the alpha4 cytoplasmic domain
      binds tightly to paxillin, a signaling adaptor protein, leading to increased cell
      migration and an altered cytoskeletal organization that results in reduced cell
      spreading. The alpha4 tail contains potential phosphorylation sites clustered in
      its core paxillin binding region. We now report that the alpha4 tail is
      phosphorylated in vitro and in vivo. Furthermore, Ser(988) is a major
      phosphorylation site. Using antibodies specific for Ser(988)-phosphorylated
      alpha4, we found the stoichiometry of alpha4 phosphorylation varied in different
      cells. However, >60% of alpha4 was phosphorylated in Jurkat T cells.
      Phosphorylation at Ser(988) blocked paxillin binding to the alpha4 tail. A
      phosphorylation-mimicking mutant of alpha4 (alpha4S988D) blocked paxillin binding
      and reversed the inhibitory effect of alpha4 on cell spreading. Consequently,
      alpha4 phosphorylation is a biochemical mechanism to modulate paxillin binding to
      alpha4 integrins with consequent regulation of alpha4 integrin-dependent cellular
      functions.

PMID- 11533026
TI  - Netrin stimulates tyrosine phosphorylation of the UNC-5 family of netrin
      receptors and induces Shp2 binding to the RCM cytodomain.
AB  - Caenorhabditis elegans UNC-5 and its mammalian homologues such as RCM are
      receptors for the secreted axon guidance cue UNC-6/netrin and are required to
      mediate the repulsive effects of UNC-6/netrin on growth cones. We find that C.
      elegans UNC-5 and mouse RCM are phosphorylated on tyrosine in vivo. C. elegans
      UNC-5 tyrosine phosphorylation is reduced in unc-6 null mutants, and RCM tyrosine
      phosphorylation is induced by netrin-1 in transfected HEK-293 cells,
      demonstrating that phosphorylation of UNC-5 proteins is enhanced by UNC-6/netrin
      stimulation in both worms and mammalian cells. An activated Src tyrosine kinase
      induces phosphorylation of RCM at multiple cytoplasmic tyrosine residues creating
      potential binding sites for cytoplasmic signaling proteins. Indeed, the NH2
      terminal SH2 domain of the Shp2 tyrosine phosphatase bound specifically to a
      Tyr(568) RCM phosphopeptide. Furthermore, Shp2 associated with RCM in a netrin
      dependent manner in transfected cells, and co-immunoprecipitated with RCM from an
      embryonic mouse brain lysate. A Y568F mutant RCM receptor failed to bind Shp2 and
      was more highly phosphorylated on tyrosine than the wild type receptor. These
      results suggest that netrin-stimulated phosphorylation of RCM Tyr(568) recruits
      Shp2 to the cell membrane where it can potentially modify RCM phosphorylation and
      function.

PMID- 11533027
TI  - Prion protein fragment PrP-(106-126) induces apoptosis via mitochondrial
      disruption in human neuronal SH-SY5Y cells.
AB  - The synthetic peptide PrP-(106-126) has previously been shown to be neurotoxic.
      Here, for the first time, we report that it induces apoptosis in the human
      neuroblastoma cell line SH-SY5Y. The earliest detectable apoptotic event in this
      system is the rapid depolarization of mitochondrial membranes, occurring
      immediately upon treatment of cells with PrP-(106-126). Subsequent to this,
      cytochrome c release and caspase activation were observed. Caspase inhibitors
      demonstrated that while the peptide activates caspases they are not an absolute
      requirement for apoptosis. Parallel to caspase activation, PrP-(106-126) was also
      observed to trigger a rise in intracellular calcium through release of
      mitochondrial calcium stores. This leads to the activation of calpains, another
      family of proteases. A calpain inhibitor demonstrated that while calpains are
      activated by the peptide they also are not an absolute requirement for apoptosis.
      Interestingly a combination of caspase and calpain inhibitors significantly
      inhibited apoptosis. This illustrates alternative pathways leading to apoptosis
      via caspases and calpains and that blocking both pathways is required to inhibit
      apoptosis. These results implicate the mitochondrion as a primary site of action
      of PrP-(106-126).

PMID- 11533028
TI  - The phosphoglucose isomerase from the hyperthermophilic archaeon Pyrococcus
      furiosus is a unique glycolytic enzyme that belongs to the cupin superfamily.
AB  - Pyrococcus furiosus uses a variant of the Embden-Meyerhof pathway during growth
      on sugars. All but one of the genes that encode the glycolytic enzymes of P.
      furiosus have previously been identified, either by homology searching of its
      genome or by reversed genetics. We here report the isolation of the missing link
      of the pyrococcal glycolysis, the phosphoglucose isomerase (PGI), which was
      purified to homogeneity from P. furiosus and biochemically characterized. The P.
      furiosus PGI, a dimer of identical 23.5-kDa subunits, catalyzes the reversible
      isomerization of glucose 6-phosphate to fructose 6-phosphate, with K(m) values of
      1.99 and 0.63 mm, respectively. An optimum pH of 7.0 has been determined in both
      directions, and at its optimum temperature of 90 degrees C the enzyme has a half
      life of 2.4 h. The N-terminal sequence was used for the identification of the
      pgiA gene in the P. furiosus genome. The pgiA transcription start site has been
      determined, and a monocistronic messenger was detected in P. furiosus during
      growth on maltose and pyruvate. The pgiA gene was functionally expressed in
      Escherichia coli BL21(DE3). The deduced amino acid sequence of this first
      archaeal PGI revealed that it is not related to its bacterial and eukaryal
      counterparts. In contrast, this archaeal PGI shares similarity with the cupin
      superfamily that consists of a variety of proteins that are generally involved in
      sugar metabolism in both prokaryotes and eukaryotes. As for the P. furiosus PGI,
      distinct phylogenetic origins have previously been reported for other enzymes
      from the pyrococcal glycolytic pathway. Apparently, convergent evolution by
      recruitment of several unique enzymes has resulted in the unique Pyrococcus
      glycolysis.

PMID- 11533029
TI  - Recovering antibody secretion using a hapten ligand as a chemical chaperone.
AB  - Engineered antibodies have come to the forefront as research reagents and
      clinical therapeutics. However, reduced stability or expression levels pose a
      major problem with many engineered antibodies. As a model for understanding
      functional consequences of variable region mutation, we have studied the assembly
      and trafficking of anti-phenylphosphocholine antibodies. Previously, we
      identified severe secretion defects because of mutations in the heavy chain
      second complementarity determining region, which is involved in antigen binding.
      Here we demonstrate that immunoglobulin secretion is increased up to 27-fold by
      incubating stably transfected PCG1-1 cells with cognate hapten p
      nitrophenylphosphocholine. Secretion was unaffected by nonbinding analogs.
      Radiotracer and metabolic labeling experiments demonstrated specific cellular
      uptake of p-nitrophenylphosphocholine and increased intracellular heavy and light
      chain assembly. Brefeldin A inhibited hapten-mediated immunoglobulin secretion
      but not assembly, indicating that assembly occurs early within the biosynthetic
      pathway. Recovery of secretion correlated with antigen binding capacity,
      suggesting that the rescue mechanism involves stabilization of heavy and light
      chain variable domains. This model system provides the first demonstration that
      cognate ligands can increase intracellular assembly of functional anti-hapten
      antibody within mammalian cells and suggests that small molecules of appropriate
      specificity and affinity acting as chemical chaperones may find application for
      increasing or regulating immunoglobulin expression.

PMID- 11533030
TI  - Cell permeant polyphosphoinositide-binding peptides that block cell motility and
      actin assembly.
AB  - Polyphosphoinositides (PPIs) affect the localization and activities of many
      cellular constituents, including actin-modulating proteins. Several classes of
      polypeptide sequences, including pleckstrin homology domains, FYVE domains, and
      short linear sequences containing predominantly hydrophobic and cationic residues
      account for phosphoinositide binding by most such proteins. We report that a ten
      residue peptide derived from the phosphatidylinositol 4,5-bisphosphate (PIP(2))
      binding region in segment 2 of gelsolin, when coupled to rhodamine B has potent
      PIP(2) binding activity in vitro; crosses the cell membrane of fibroblasts,
      platelets, melanoma cells, and neutrophils by a process not involving
      endocytosis; and blocks cell motility. This peptide derivative transiently
      disassembles actin filament structures in GFP-actin-expressing NIH3T3 fibroblasts
      and prevents thrombin- or chemotactic peptide-stimulated actin assembly in
      platelets and neutrophils, respectively, but does not block the initial [Ca(2+)]
      increase caused by these agonists. The blockage of actin assembly and motility is
      transient, and cells recover motility within an hour after their immobilization
      by 5-20 microm peptide. This class of reagents confirms the critical relation
      between inositol lipids and cytoskeletal structure and may be useful to probe the
      location and function of polyphosphoinositides in vivo.

PMID- 11533031
TI  - Identification of a site on mannan-binding lectin critical for enhancement of
      phagocytosis.
AB  - Mannan-binding lectin (MBL) constitutes an important part of the human innate
      immune defense system. It has been shown to mediate the activation of complement
      upon binding to specific microbial carbohydrate motifs, to directly opsonize
      organisms, and to enhance the phagocytosis of targets suboptimally opsonized with
      IgG or complement components C3b or C4b. This enhancement of phagocytic activity
      induced by MBL and other molecules that contain a collagen-like region contiguous
      with a pattern recognition domain is mediated by a 126,000 M(r) surface
      glycoprotein, designated C1qR(P). Although it has been known that the collagen
      like domain of these "defense collagens" contains the interaction site(s) that
      triggers this enhancement of uptake, the specific interaction site has not been
      identified. To address this issue, wild type and mutant MBL constructs were
      generated, inserted into baculovirus, expressed in Sf9 cells, and the recombinant
      MBL (rMBL) proteins purified by mannan affinity chromatography. The effect of
      wild type and mutant rMBL on the phagocytosis of targets suboptimally opsonized
      with IgG or with IgM and C4b by human peripheral blood monocytes was then
      assessed. Two mutants, one of which has five GXY triplets deleted below the kink
      region of MBL and the other one having only two of the GXY triplets deleted below
      the kink, failed to enhance phagocytosis, suggesting the importance of the
      specific sequence GEKGEP in stimulating phagocytic activity. Similar sequences
      were detected in other defense collagens, implicating the consensus motif
      GE(K/Q/R)GEP as critical in mediating the enhancement of phagocytosis through
      C1qR(P.) Clarification of specific ligand-C1qR(P) interactions should facilitate
      the investigation of the signal transduction processes involved in the cell
      activation, as well as provide the basis for the design of specific modulators of
      the functions mediated by this receptor.

PMID- 11533032
TI  - Formation of crystalloid endoplasmic reticulum induced by expression of
      synaptotagmin lacking the conserved WHXL motif in the C terminus. Structural
      importance of the WHXL motif in the C2B domain.
AB  - Synaptotagmin (Syt) is a family of type I membrane proteins that consists of a
      single transmembrane domain, a spacer domain, two Ca(2+)-binding C2 domains, and
      a short C terminus. We recently showed that deletion of the short C terminus (17
      amino acids) of Syt IV prevented the Golgi localization of Syt IV proteins in
      PC12 cells and induced granular structures of various sizes in the cell body by
      an unknown mechanism (Fukuda, M., Ibata, K., and Mikoshiba, K. (2001) J.
      Neurochem. 77, 730-740). In this study we showed by electron microscopy that
      these structures are crystalloid endoplasmic reticulum (ER), analyzed the
      mechanism of its induction, and demonstrated that: (a) mutation or deletion of
      the evolutionarily conserved WHXL motif in the C terminus of the synaptotagmin
      family (Syt DeltaC) destabilizes the C2B domain structure (i.e. causes misfolding
      of the protein), probably by disrupting the formation of stable anti-parallel
      beta-sheets between the beta-1 and beta-8 strands of the C2B domain; (b) the
      resulting malfolded proteins accumulate in the ER rather than being transported
      to other membrane structures (e.g. the Golgi apparatus), with the malfolded
      proteins also inducing the expression of BiP (immunoglobulin binding protein),
      one of the ER stress proteins; and (c) the ERs in which the Syt DeltaC proteins
      have accumulated associate with each other as a result of oligomerization
      capacity of the synaptotagmin family, because the Syt IDeltaC mutant, which lacks
      oligomerization activity, cannot induce crystalloid ER. Our findings indicate
      that the conserved WHXL motif is important not only for protein interaction site
      but for proper folding of the C2B domain.

PMID- 11533033
TI  - Lipid binding-induced conformational change in human apolipoprotein E. Evidence
      for two lipid-bound states on spherical particles.
AB  - Apolipoprotein (apo) E contains two structural domains, a 22-kDa (amino acids 1
      191) N-terminal domain and a 10-kDa (amino acids 223-299) C-terminal domain. To
      better understand apoE-lipid interactions on lipoprotein surfaces, we determined
      the thermodynamic parameters for binding of apoE4 and its 22- and 10-kDa
      fragments to triolein-egg phosphatidylcholine emulsions using a centrifugation
      assay and titration calorimetry. In both large (120 nm) and small (35 nm)
      emulsion particles, the binding affinities decreased in the order 10-kDa fragment
      approximately 34-kDa intact apoE4 > 22-kDa fragment, whereas the maximal binding
      capacity of intact apoE4 was much larger than those of the 22- and 10-kDa
      fragments. These results suggest that at maximal binding, the binding behavior of
      intact apoE4 is different from that of each fragment and that the N-terminal
      domain of intact apoE4 does not contact lipid. Isothermal titration calorimetry
      measurements showed that apoE binding to emulsions was an exothermic process.
      Binding to large particles is enthalpically driven, and binding to small
      particles is entropically driven. At a low surface concentration of protein, the
      binding enthalpy of intact apoE4 (-69 kcal/mol) was approximately equal to the
      sum of the enthalpies for the 22- and 10-kDa fragments, indicating that both the
      22- and 10-kDa fragments interact with lipids. In a saturated condition, however,
      the binding enthalpy of intact apoE4 (-39 kcal/mol) was less exothermic and
      rather similar to that of each fragment, supporting the hypothesis that only the
      C-terminal domain of intact apoE4 binds to lipid. We conclude that the N-terminal
      four-helix bundle can adopt either open or closed conformations, depending upon
      the surface concentration of emulsion-bound apoE.

PMID- 11533034
TI  - Three-dimensional structure of the vacuolar ATPase proton channel by electron
      microscopy.
AB  - Vacuolar ATPases are ATP hydrolysis-driven proton pumps found in the endomembrane
      system of eucaryotic cells where they are involved in pH regulation. We have
      determined the three-dimensional structure of the proton channel domain of the
      vacuolar ATPase from bovine brain clathrin-coated vesicles by electron microscopy
      at 21 A resolution. The model shows an asymmetric protein ring with two small
      openings on the luminal side and one large opening on the cytoplasmic side. The
      central hole on the luminal side is covered by a globular protein, while the
      cytoplasmic opening is covered by two elongated proteins arranged in a collar
      like fashion.

PMID- 11533035
TI  - Crystal structure and biophysical properties of a complex between the N-terminal
      SNARE region of SNAP25 and syntaxin 1a.
AB  - SNARE proteins are required for intracellular membrane fusion. In the neuron, the
      plasma membrane SNAREs syntaxin 1a and SNAP25 bind to VAMP2 found on
      neurotransmitter-containing vesicles. These three proteins contain "SNARE
      regions" that mediate their association into stable tetrameric coiled-coil
      structures. Syntaxin 1a contributes one such region, designated H3, and SNAP25
      contributes two SNARE regions to the fusogenic complex with VAMP2. Syntaxin 1a H3
      (syn1aH3) and SNAP25 can form a stable assembly, which can then be bound by VAMP2
      to form the full SNARE complex. Here we show that syn1aH3 can also form a stable
      but kinetically trapped complex with the N-terminal SNARE region of SNAP25
      (S25N). The crystal structure of this complex reveals an extended parallel four
      helix bundle similar to that of the core SNARE and the syn1aH3-SNAP25 complexes.
      The inherent ability of syn1aH3 and S25N to associate stably in vitro implies
      that the intracellular fusion machinery must prevent formation of, or remove, any
      non-productive complexes. Comparison with the syn1aH3-SNAP25 complex suggests
      that the linkage of the N- and C-terminal SNAP25 SNARE regions is kinetically
      advantageous in preventing formation of the non-productive syn1aH3-S25N complex.
      We also demonstrate that the syn1aH3-S25N complex can be disassembled by alpha
      SNAP and N-ethylmaleimide-sensitive factor.

PMID- 11533036
TI  - Phosphorylation and cell cycle-dependent regulation of Na+/H+ exchanger
      regulatory factor-1 by Cdc2 kinase.
AB  - Na(+)/H(+) exchanger regulatory factor (NHERF)-1 is a PDZ domain-containing
      adaptor protein known to bind to various receptors, channels, cytoskeletal
      elements, and cytoplasmic signaling proteins. We report here that the
      phosphorylation state of NHERF-1 is profoundly regulated by the cell cycle: NHERF
      1 in HeLa cells is hyperphosphorylated in mitosis phase and much less
      phosphorylated at other points of the cell cycle. This mitosis phase-dependent
      phosphorylation of NHERF-1 could be blocked by roscovitine, consistent with
      phosphorylation by cyclin-dependent kinases. In vitro studies with purified NHERF
      1 fusion proteins and purified kinases revealed that NHERF-1 was robustly
      phosphorylated by the cyclin-dependent kinase Cdc2. In contrast, the NHERF-1
      relative NHERF-2 was not phosphorylated at all by Cdc2. NHERF-1 possesses two
      serines (Ser(279) and Ser(301)) that conform to the SPX(K/R) motif preferred for
      phosphorylation by Cdc2. Mutation of either of these serines reduced Cdc2
      mediated phosphorylation of NHERF-1 in vitro, and mutation of both residues
      together completely abolished Cdc2-mediated phosphorylation. When the S279A/S301A
      NHERF-1 mutant was expressed in cells, it failed to exhibit the mitosis phase
      dependent phosphorylation observed with wild-type NHERF-1. Mutation of both
      Ser(279) and Ser(301) to aspartate, to mimic Cdc2 phosphorylation of NHERF-1,
      resulted in a NHERF-1 mutant with a markedly impaired ability to oligomerize in
      vitro. Similarly, endogenous NHERF-1 from lysates of mitosis phase HeLa cells
      exhibited a markedly reduced ability to oligomerize relative to endogenous NHERF
      1 from lysates of interphase HeLa cells. Mitosis phase NHERF-1 furthermore
      exhibited the ability to associate with Pin1, a WW domain-containing
      peptidylprolyl isomerase that does not detectably bind to NHERF-1 in interphase
      lysates. The association of NHERF-1 with Pin1 facilitated dephosphorylation of
      NHERF-1, as shown in experiments in which cellular Pin1 activity was blocked by
      the selective inhibitor juglone. These data reveal that cellular NHERF-1 is
      phosphorylated during mitosis phase by Cdc2 at Ser(279) and Ser(301) and that
      this phosphorylation regulates NHERF-1 oligomerization and association with Pin1.

PMID- 11533037
TI  - Mechanism of vitamin C inhibition of cell death induced by oxidative stress in
      glutathione-depleted HL-60 cells.
AB  - Vitamin C is a well known antioxidant whose precise role in protecting cells from
      oxidative challenge is uncertain. In vitro results have been confounded by pro
      oxidant effects of ascorbic acid and an overlapping role of glutathione. We used
      HL-60 cells as a model to determine the precise and independent role of vitamin C
      in cellular protection against cell death induced by oxidative stress. HL-60
      cells do not depend on glutathione to transport or reduce dehydroascorbic acid.
      Depletion of glutathione rendered the HL-60 cells highly sensitive to cell death
      induced by H2O2, an effect that was not mediated by changes in the activities of
      glutathione reductase, glutathione peroxidase, catalase, or superoxide dismutase.
      The increased sensitivity to oxidative stress was largely reversed when
      glutathione-depleted cells were preloaded with ascorbic acid by exposure to
      dehydroascorbic acid. Resistance to H2O2 treatment in cells loaded with vitamin C
      was accompanied by intracellular consumption of ascorbic acid, generation of
      dehydroascorbic acid, and a decrease in the cellular content of reactive oxygen
      species. Some of the dehydroascorbic acid generated was exported out of the cells
      via the glucose transporters. Our data indicate that vitamin C is an important
      independent antioxidant in protecting cells against death from oxidative stress.

PMID- 11533038
TI  - Hypochlorous acid oxygenates the cysteine switch domain of pro-matrilysin (MMP
      7). A mechanism for matrix metalloproteinase activation and atherosclerotic
      plaque rupture by myeloperoxidase.
AB  - Myeloperoxidase uses hydrogen peroxide (H2O2) to generate hypochlorous acid
      (HOCl), a potent cytotoxic oxidant. We demonstrate that HOCl regulates the
      activity of matrix metalloproteinase-7 (MMP-7, matrilysin) in vitro, suggesting
      that this oxidant activates MMPs in the artery wall. Indeed, both MMP-7 and
      myeloperoxidase were colocalized to lipid-laden macrophages in human
      atherosclerotic lesions. A highly conserved domain called the cysteine switch has
      been proposed to regulate MMP activity. When we exposed a synthetic peptide that
      mimicked the cysteine switch to HOCl, HPLC analysis showed that the thiol residue
      reacted rapidly, generating a near-quantitative yield of products. Tandem mass
      spectrometric analysis identified the products as sulfinic acid, sulfonic acid,
      and a dimer containing a disulfide bridge. In contrast, the peptide reacted
      slowly with H2O2, and the only product was the disulfide. Moreover, HOCl markedly
      activated pro-MMP-7, an MMP expressed at high levels in lipid-laden macrophages
      in vivo. Tandem mass spectrometric analysis of trypsin digests revealed that the
      thiol residue of the enzyme's cysteine switch domain had been converted to
      sulfinic acid. Thiol oxidation was associated with autolytic cleavage of pro-MMP
      7, strongly suggesting that oxygenation activates the latent enzyme. In contrast,
      H2O2 failed to oxidize the thiol residue of the protein or activate the enzyme.
      Thus, HOCl activates pro-MMP-7 by converting the thiol residue of the cysteine
      switch to sulfinic acid. This activation mechanism is distinct from the well
      studied proteolytic cleavage of MMP pro-enzymes. Our observations raise the
      possibility that HOCl generated by myeloperoxidase contributes to MMP activation,
      and therefore to plaque rupture, in the artery wall. HOCl and other oxidants
      might regulate MMP activity by the same mechanism in a variety of inflammatory
      conditions.

PMID- 11533039
TI  - Reduction of interchain disulfide bonds precedes the dislocation of Ig-mu chains
      from the endoplasmic reticulum to the cytosol for proteasomal degradation.
AB  - Proteins that fail to fold or assemble in the endoplasmic reticulum (ER) are
      generally dislocated across the membrane to be degraded by cytosolic proteasomes.
      To investigate how the quality control machinery handles individual subunits that
      are part of covalent oligomers, we have analyzed the fate of transport-competent
      Ig light (L) chains that form disulfide bonds with short-lived mu heavy chains.
      When expressed alone, L chains are secreted. In cells producing excess mu, most L
      chains are retained in the ER as covalent mu-L or mu2-L2 complexes. While mu
      chains present in these complexes are degraded by proteasomes, L chains are
      stable. Few L chains are secreted; most reassociate with newly synthesized mu
      chains. Therefore, interchain disulfide bonds are reduced in the ER lumen before
      the dislocation of mu chains in a site from which freed L chains can be rapidly
      reinserted in the assembly line. The ER can thus sustain the simultaneous
      formation and reduction of disulfide bonds.

PMID- 11533040
TI  - Dehydroepiandrosterone sulfotransferase gene induction by bile acid activated
      farnesoid X receptor.
AB  - Dehydroepiandrosterone sulfotransferase (STD) is a hydroxysteroid sulfo
      conjugating enzyme with preferential substrate specificity for C-19 androgenic
      steroids and C-24 bile acids. STD is primarily expressed in the liver, intestine
      and adrenal cortex. Earlier studies have shown that androgens inhibit the rat Std
      promoter function through a negative androgen response region located between 
      235 and -310 base pair positions (Song, C. S., Jung, M. H., Kim, S. C., Hassan,
      T., Roy, A. K., and Chatterjee, B. (1998) J. Biol. Chem. 273, 21856-21866). Here
      we report that the primary bile acid chenodeoxycholic acid (CDCA) also acts as an
      important regulator of the Std gene promoter. CDCA is a potent inducer of the Std
      gene, and its inducing effect is mediated through the bile acid-activated
      farnesoid X receptor (FXR), a recently characterized member of the nuclear
      receptor superfamily. The ligand-activated FXR acts as a heterodimer with the 9
      cis-retinoic acid receptor (RXR) and regulates the Std gene by binding to an
      upstream region at base pair positions -169 to -193. This specific binding region
      was initially identified by bile acid responsiveness of the progressively deleted
      forms of the Std promoter in transfected HepG2 hepatoma and enterocyte-like Caco
      2 cells. Subsequently, the precise RXR/FXR binding position was established by
      protein-DNA interaction using in vitro footprinting and electrophoretic mobility
      shift analyses. Unlike all other previously characterized FXR target genes, which
      contain an inverted repeat (IR) of the consensus hexanucleotide half-site
      (A/G)G(G/T)TCA with a single nucleotide spacer (IR-1), the bile acid response
      element of the Std promoter does not contain any spacer between the two
      hexanucleotide repeats (IR-0). A promoter-reporter construct carrying three
      tandem copies of the IR-0 containing -169/-193 element, linked to a minimal
      thymidine kinase promoter, can be stimulated more than 70-fold in transfected
      Caco-2 cells upon CDCA treatment. Autoregulation of the STD gene by its bile acid
      substrate may provide an important contributing role in the enterohepatic bile
      acid metabolism and cholesterol homeostasis.

PMID- 11533041
TI  - Identification of a novel interaction of 14-3-3 with p190RhoGEF.
AB  - Activation of Rho GTPases by guanine nucleotide exchange factors (GEFs) mediates
      a broad range of cytoskeletal alterations that determine cell shape. In the
      nervous system, Rho GTPases are essential for establishing highly asymmetrical
      neuronal forms and may fine-tune the shape of dendrites in differentiated
      neurons. p190RhoGEF is a brain-enriched, RhoA-specific GEF whose highly
      interactive C-terminal domain provides potential linkage to multiple pathways in
      the cell. In the present study, a yeast two-hybrid screen was used to identify 14
      3-3eta and 14-3-3epsilon as additional binding partners of p190RhoGEF.
      Interactions between p190RhoGEF and 14-3-3eta were confirmed biochemically and by
      colocalization of the respective proteins when fused to fluorescent markers and
      transfected in neuronal cells. We also mapped a unique phosphorylation
      independent binding site (I(1370)QAIQNL) in p190RhoGEF. Deletion of the binding
      site abolished interactions in vitro as well as the ability of 14-3-3eta to alter
      the cytoplasmic aggregation of p190RhoGEF in cotransfected cells. The findings
      suggest a potential role for 14-3-3 in modulating p190RhoGEF activity or in
      linking p190RhoGEF to the activities of other pathways in the neuron.

PMID- 11533042
TI  - K+ stimulates specifically the autokinase activity of purified and reconstituted
      EnvZ of Escherichia coli.
AB  - The histidine kinase/response regulator system EnvZ/OmpR of Escherichia coli
      regulates transcription of the genes ompF and ompC, encoding two porins of the
      outer membrane. Although the total amount of OmpF and OmpC remains constant, the
      relative levels of the two proteins fluctuate in a reciprocal manner depending on
      medium osmolality. The membrane-anchored sensor EnvZ somehow monitors changes in
      environmental osmolality. To characterize the nature of the stimulus perceived by
      EnvZ, this protein was overproduced, purified, and reconstituted into
      proteoliposomes. Autokinase activity of purified and reconstituted EnvZ was
      stimulated by an increase of the K(+) concentration. Rb(+), Na(+), and NH4(+)
      also stimulated the activity but to a smaller extent, whereas an osmotic upshift
      imposed by various sugars or increasing concentrations of glycine betaine,
      proline, or Tris/MES were without influence. Neither the transfer of the
      phosphoryl group from EnvZ approximately P to OmpR nor the EnvZ-mediated OmpR
      approximately P dephosphorylation were affected by one of the tested solutes.
      Experiments with the reconstructed signal transduction cascade including DNA
      fragments demonstrated a substantial increase of the amount of phosphorylated
      OmpR in the presence of K(+) and to a lower extent in the presence of Na(+),
      Rb(+), and NH4(+). Various K(+) salts were tested indicating that the determined
      effects were K(+)-specific and not dependent on the anion. In a further in vitro
      test system, which utilizes right-side-out membrane vesicles, the K(+)-specific
      activation of EnvZ autokinase from the luminal side was confirmed. These results
      clearly indicate a regulation of EnvZ autokinase activity by monovalent ions,
      specifically K(+). Whether K(+) accumulation, which is one of the first responses
      of E. coli after an osmotic upshift, is related to the stimulation of the EnvZ
      autokinase activity in vivo is discussed.

PMID- 11533043
TI  - beta-Arrestin-mediated ADP-ribosylation factor 6 activation and beta 2-adrenergic
      receptor endocytosis.
AB  - beta-Arrestins are multifunctional adaptor proteins known to regulate
      internalization of agonist-stimulated G protein-coupled receptors by linking them
      to endocytic proteins such as clathrin and AP-2. Here we describe a previously
      unappreciated mechanism by which beta-arrestin orchestrates the process of
      receptor endocytosis through the activation of ADP-ribosylation factor 6 (ARF6),
      a small GTP-binding protein. Involvement of ARF6 in the endocytic process is
      demonstrated by the ability of GTP-binding defective and GTP hydrolysis-deficient
      mutants to inhibit internalization of the beta(2)-adrenergic receptor. The
      importance of regulation of ARF6 function is shown by the ability of the ARF
      GTPase-activating protein GIT1 to inhibit and of the ARF nucleotide exchange
      factor, ARNO, to enhance receptor endocytosis. Endogenous beta-arrestin is found
      in complex with ARNO. Upon agonist stimulation of the receptor, beta-arrestin
      also interacts with the GDP-liganded form of ARF6, thereby facilitating ARNO
      promoted GTP loading and activation of the G protein. Thus, the agonist-driven
      formation of a complex including beta-arrestin, ARNO, and ARF6 provides a
      molecular mechanism that explains how the agonist-stimulated receptor recruits a
      small G protein necessary for the endocytic process and controls its activation.

PMID- 11533044
TI  - Akt1/PKBalpha is required for normal growth but dispensable for maintenance of
      glucose homeostasis in mice.
AB  - The serine-threonine kinase Akt, also known as protein kinase B (PKB), is an
      important effector for phosphatidylinositol 3-kinase signaling initiated by
      numerous growth factors and hormones. Akt2/PKBbeta, one of three known mammalian
      isoforms of Akt/PKB, has been demonstrated recently to be required for at least
      some of the metabolic actions of insulin (Cho, H., Mu, J., Kim, J. K.,
      Thorvaldsen, J. L., Chu, Q., Crenshaw, E. B., Kaestner, K. H., Bartolomei, M. S.,
      Shulman, G. I., and Birnbaum, M. J. (2001) Science 292, 1728-1731). Here we show
      that mice deficient in another closely related isoform of the kinase,
      Akt1/PKBalpha, display a conspicuous impairment in organismal growth. Akt1(-/-)
      mice demonstrated defects in both fetal and postnatal growth, and these persisted
      into adulthood. However, in striking contrast to Akt2/PKBbeta null mice,
      Akt1/PKBalpha-deficient mice are normal with regard to glucose tolerance and
      insulin-stimulated disposal of blood glucose. Thus, the characterization of the
      Akt1 knockout mice and its comparison to the previously reported Akt2 deficiency
      phenotype reveals the non-redundant functions of Akt1 and Akt2 genes with respect
      to organismal growth and insulin-regulated glucose metabolism.

PMID- 11533045
TI  - High intensity ERK signal mediates hepatocyte growth factor-induced proliferation
      inhibition of the human hepatocellular carcinoma cell line HepG2.
AB  - Hepatocyte growth factor (HGF) induces growth stimulation of a variety of cell
      types, but it also induces growth inhibition of several types of tumor cell
      lines. The molecular mechanism of the HGF-induced growth inhibition of tumor
      cells remains obscure. We have investigated the intracellular signaling pathway
      involved in the antiproliferative effect of HGF on the human hepatocellular
      carcinoma cell line HepG2. HGF induced strong activation of ERK in HepG2 cells.
      Although the serum-dependent proliferation of HepG2 cells was inhibited by the
      MEK inhibitor PD98059 in a dose-dependent manner, 10 microM PD98059 reduced the
      HGF-induced strong activation of ERK to a weak activation; and as a result, the
      proliferation inhibited by HGF was completely restored. Above or below this
      specific concentration, the restoration was incomplete. Expression of
      constitutively activated Ha-Ras, which induces strong activation of ERK, led to
      the proliferation inhibition of HepG2 cells, as was observed in HGF-treated HepG2
      cells. This inhibition was suppressed by the MEK inhibitor. Furthermore, HGF
      treatment and expression of constitutively activated Ha-Ras changed the
      hyperphosphorylated form of the retinoblastoma tumor suppressor gene product pRb
      to the hypophosphorylated form. This change was inhibited by the same
      concentration of MEK inhibitor needed to suppress the proliferation inhibition.
      These results suggest that ERK activity is required for both the stimulation and
      inhibition of proliferation of HepG2 cells; that the level of ERK activity
      determines the opposing proliferation responses; and that HGF-induced
      proliferation inhibition is caused by cell cycle arrest, which results from pRb
      being maintained in its active hypophosphorylated form via a high-intensity ERK
      signal in HepG2 cells.

PMID- 11533046
TI  - Free cholesterol loading of macrophages is associated with widespread
      mitochondrial dysfunction and activation of the mitochondrial apoptosis pathway.
AB  - Macrophage death in advanced atherosclerotic lesions leads to lesional necrosis
      and possibly plaque rupture and acute vascular occlusion. Among the likely causes
      of lesional macrophage death is intracellular accumulation of excess free
      cholesterol (FC), which is known to occur in vivo. We recently showed that FC
      loading of macrophages causes apoptosis, approximately 50% of which is mediated
      by activation of cell-surface FasL and triggering of the Fas pathway (Yao, P. M.,
      and Tabas, I. (2000) J. Biol. Chem. 275, 23807-23813). To elucidate other
      pathways of death in FC-loaded macrophages, we investigated mitochondrial
      transmembrane potential (DeltaPsi(m)) and the mitochondrial apoptosis pathway in
      FC-loaded mouse peritoneal macrophages. Starting between 3 and 6 h of FC loading,
      DeltaPsi(m) was markedly decreased in the majority of macrophages and was
      independent of the Fas pathway. The decrease in DeltaPsi(m) by FC loading was not
      prevented by GSH, thus distinguishing it from 7-ketocholesterol-induced
      mitochondrial dysfunction. Cytochrome c release into the cytosol was noted by 4 h
      of FC loading, and activation of caspase-9 and effector caspases was observed at
      6 h. Finally, we found that both cellular and mitochondrial levels of the pro
      apoptotic protein Bax were increased severalfold as early as 4 h after FC
      loading. Thus, FC loading, perhaps via increased levels of Bax and/or cholesterol
      overloading of mitochondria, triggers cytochrome c release and activation of
      caspase-9 and the effector caspases, leading to macrophage apoptosis. These
      findings and our previous data support a model in which FC loading of macrophages
      promotes a dual program of caspase-mediated death.

PMID- 11533047
TI  - Characterization of the rat GRIK5 kainate receptor subunit gene promoter and its
      intragenic regions involved in neural cell specificity.
AB  - The GRIK5 (glutamate receptor ionotropic kainate-5) gene encodes the kainate
      preferring glutamate receptor subunit KA2. The GRIK5 promoter is TATA-less and GC
      rich, with multiple consensus initiator sequences. Transgenic mouse lines
      carrying 4 kilobases of the GRIK5 5'-flanking sequence showed lacZ reporter
      expression predominantly in the nervous system. Reporter assays in central glial
      (CG-4) and non-neural cells indicated that a 1200-base pair (bp) 5'-flanking
      region could sustain neural cell-specific promoter activity. Transcriptional
      activity was associated with the formation of a transcription factor IID
      containing complex on an initiator sequence located 1100 bp upstream of the first
      intron. In transfection studies, deletion of exonic sequences downstream of the
      promoter resulted in reporter gene activity that was no longer neural cell
      specific. When placed downstream of the GRIK5 promoter, a 77-bp sequence from the
      deleted fragment completely silenced reporter expression in NIH3T3 fibroblasts
      while attenuating activity in CG-4 cells. Analysis of the 77-bp sequence revealed
      a functional SP1-binding site and a sequence resembling a neuron-restrictive
      silencer element. The latter sequence, however, did not display cell-specific
      binding of REST-like proteins. Our studies thus provide evidence for intragenic
      control of GRIK5 promoter activity and suggest that elements contributing to
      tissue-specific expression are contained within the first exon.

PMID- 11533048
TI  - Human glutathione transferase P1-1 and nitric oxide carriers; a new role for an
      old enzyme.
AB  - S-Nitrosoglutathione and the dinitrosyl-diglutathionyl iron complex are involved
      in the storage and transport of NO in biological systems. Their interactions with
      the human glutathione transferase P1-1 may reveal an additional physiological
      role for this enzyme. In the absence of GSH, S-nitrosoglutathione causes rapid
      and stable S-nitrosylation of both the Cys(47) and Cys(101) residues. Ion spray
      ionization-mass spectrometry ruled out the possibility of S-glutathionylation and
      confirms the occurrence of a poly-S-nitrosylation in GST P1-1. S-Nitrosylation of
      Cys(47) lowers the affinity 10-fold for GSH, but this negative effect is
      minimized by a half-site reactivity mechanism that protects one Cys(47)/dimer
      from nitrosylation. Thus, glutathione transferase P1-1, retaining most of its
      original activity, may act as a NO carrier protein when GSH depletion occurs in
      the cell. The dinitrosyl-diglutathionyl iron complex, which is formed by S
      nitrosoglutathione decomposition in the presence of physiological concentrations
      of GSH and traces of ferrous ions, binds with extraordinary affinity to one
      active site of this dimeric enzyme (K(i) < 10(-12) m) and triggers negative
      cooperativity in the vacant subunit (K(i) = 10(-9) m). The complex bound to the
      enzyme is stable for hours, whereas in the free form and at low concentrations,
      its life time is only a few minutes. ESR and molecular modeling studies provide a
      reasonable explanation of this strong interaction, suggesting that Tyr(7) and
      enzyme-bound GSH could be involved in the coordination of the iron atom. All of
      the observed findings suggest that glutathione transferase P1-1, by means of an
      intersubunit communication, may act as a NO carrier under different cellular
      conditions while maintaining its well known detoxificating activity toward
      dangerous compounds.

PMID- 11533049
TI  - Chlorination of guanosine and other nucleosides by hypochlorous acid and
      myeloperoxidase of activated human neutrophils. Catalysis by nicotine and
      trimethylamine.
AB  - Activated human neutrophils secrete myeloperoxidase, which generates HOCl from
      H2O2 and Cl(-). We have found that various (2'-deoxy)nucleosides react with HOCl
      to form chlorinated (2'-deoxy)nucleosides, including novel 8-chloro(2'
      deoxy)guanosine, 5-chloro(2'-deoxy)cytidine, and 8-chloro(2'-deoxy)adenosine
      formed in yields of 1.6, 1.6, and 0.2%, respectively, when 0.5 mM nucleoside
      reacted with 0.5 mM HOCl at pH 7.4. The relative chlorination, oxidation, and
      nitration activities of HOCl, myeloperoxidase, and activated human neutrophils in
      the presence and absence of nitrite were studied by analyzing 8-chloro-, 8-oxo
      7,8-dihydro-, and 8-nitro-guanosine, respectively, using guanosine as a probe. 8
      Chloroguanosine was always more easily formed than 8-oxo-7,8-dihydro- or 8-nitro
      guanosine. Using electrospray ionization tandem mass spectrometry, we show that
      several chlorinated nucleosides including 8-chloro(2'-deoxy)guanosine are formed
      following exposure of isolated DNA or RNA to HOCl. Micromolar concentrations of
      tertiary amines such as nicotine and trimethylamine dramatically enhanced
      chlorination of free (2'-deoxy)nucleosides and nucleosides in RNA by HOCl. As the
      G-463A polymorphism of the MPO gene, which strongly reduces myeloperoxidase mRNA
      expression, is associated with a reduced risk of lung cancer, chlorination damage
      of DNA /RNA and nucleosides by myeloperoxidase and its enhancement by nicotine
      may be important in the pathophysiology of human diseases associated with tobacco
      habits.

PMID- 11533050
TI  - The mechanisms by which both heterozygous peroxisome proliferator-activated
      receptor gamma (PPARgamma) deficiency and PPARgamma agonist improve insulin
      resistance.
AB  - Peroxisome proliferator-activated receptor (PPAR) gamma is a ligand-activated
      transcription factor and a member of the nuclear hormone receptor superfamily
      that is thought to be the master regulator of fat storage; however, the
      relationship between PPARgamma and insulin sensitivity is highly controversial.
      We show here that supraphysiological activation of PPARgamma by PPARgamma agonist
      thiazolidinediones (TZD) markedly increases triglyceride (TG) content of white
      adipose tissue (WAT), thereby decreasing TG content of liver and muscle, leading
      to amelioration of insulin resistance at the expense of obesity. Moderate
      reduction of PPARgamma activity by heterozygous PPARgamma deficiency decreases TG
      content of WAT, skeletal muscle, and liver due to increased leptin expression and
      increase in fatty acid combustion and decrease in lipogenesis, thereby
      ameliorating high fat diet-induced obesity and insulin resistance. Moreover,
      although heterozygous PPARgamma deficiency and TZD have opposite effects on total
      WAT mass, heterozygous PPARgamma deficiency decreases lipogenesis in WAT, whereas
      TZD stimulate adipocyte differentiation and apoptosis, thereby both preventing
      adipocyte hypertrophy, which is associated with alleviation of insulin resistance
      presumably due to decreases in free fatty acids, and tumor necrosis factor alpha,
      and up-regulation of adiponectin, at least in part. We conclude that, although by
      different mechanisms, both heterozygous PPARgamma deficiency and PPARgamma
      agonist improve insulin resistance, which is associated with decreased TG content
      of muscle/liver and prevention of adipocyte hypertrophy.

PMID- 11533051
TI  - Dual regulation of glycogen synthase kinase-3beta by the alpha1A-adrenergic
      receptor.
AB  - Catecholamines, acting through adrenergic receptors, play an important role in
      modulating the effects of insulin on glucose metabolism. Insulin activation of
      glycogen synthesis is mediated in part by the inhibitory phosphorylation of
      glycogen synthase kinase-3 (GSK-3). In this study, catecholamine regulation of
      GSK-3beta was investigated in Rat-1 fibroblasts stably expressing the alpha1A
      adrenergic receptor. Treatment of these cells with either insulin or
      phenylephrine (PE), an alpha1-adrenergic receptor agonist, induced Ser-9
      phosphorylation of GSK-3beta and inhibited GSK-3beta activity. Insulin-induced
      GSK-3beta phosphorylation is mediated by the phosphatidylinositol 3-kinase/Akt
      signaling pathway. PE treatment does not activate phosphatidylinositol 3-kinase
      or Akt (Ballou, L. M., Cross, M. E., Huang, S., McReynolds, E. M., Zhang, B. X.,
      and Lin, R. Z. (2000) J. Biol. Chem. 275, 4803-4809), but instead inhibits
      insulin-induced Akt activation and GSK-3beta phosphorylation. Experiments using
      protein kinase C (PKC) inhibitors suggest that phorbol ester-sensitive novel PKC
      and Go 6983-sensitive atypical PKC isoforms are involved in the PE-induced
      phosphorylation of GSK-3beta. Indeed, PE treatment of Rat-1 cells increased the
      activity of atypical PKCzeta, and expression of PKCzeta in COS-7 cells stimulated
      GSK-3beta Ser-9 phosphorylation. In addition, PE-induced GSK-3beta
      phosphorylation was reduced in Rat-1 cells treated with a cell-permeable PKCzeta
      pseudosubstrate peptide inhibitor. These results suggest that the alpha1A
      adrenergic receptor regulates GSK-3beta through two signaling pathways. One
      pathway inhibits insulin-induced GSK-3beta phosphorylation by blocking insulin
      activation of Akt. The second pathway stimulates Ser-9 phosphorylation of GSK
      3beta, probably via PKC.

PMID- 11533052
TI  - GSA11 encodes a unique 208-kDa protein required for pexophagy and autophagy in
      Pichia pastoris.
AB  - Cells are capable of adapting to changes in their environment by synthesizing
      needed proteins and degrading superfluous ones. Pichia pastoris synthesizes
      peroxisomal enzymes to grow in methanol medium. Upon adapting from methanol
      medium to one containing glucose, this yeast rapidly and selectively degrades
      peroxisomes by an autophagic process referred to as pexophagy. In this study, we
      have utilized a novel approach to identify genes required for this degradative
      pathway. Our approach involves the random integration of a vector containing the
      Zeocin resistance gene into the yeast genome by restriction enzyme-mediated
      integration. Cells unable to degrade peroxisomes during glucose adaptation were
      isolated, and the genes that were disrupted by the insertion of the vector were
      determined by sequencing. By using this approach, we have identified a number of
      genes required for glucose-induced selective autophagy of peroxisomes (GSA
      genes). We report here the characterization of Gsa11, a unique 208-kDa protein.
      We found that this protein is required for glucose-induced pexophagy and
      starvation-induced autophagy. Gsa11 is a cytosolic protein that becomes
      associated with one or more structures situated near the vacuole during glucose
      adaptation. The punctate localization of Gsa11 was not observed in gsa10, gsa12,
      gsa14, and gsa19 mutants. We have previously shown that Gsa9 appears to relocate
      from a compartment at the vacuole surface to regions between the vacuole and the
      peroxisomes being sequestered. In the gsa11 mutants, the vacuole only partially
      surrounded the peroxisomes, but Gsa9 was still distributed around the peroxisome
      cluster. This suggests that Gsa9 binds to the peroxisomes independent of the
      vacuole. The data also indicate that Gsa11 is not necessary for Gsa9 to interact
      with peroxisomes but acts at an intermediate event required for the vacuole to
      engulf the peroxisomes.

PMID- 11533053
TI  - Anti-atherogenic antioxidants regulate the expression and function of proteasome
      alpha-type subunits in human endothelial cells.
AB  - It has been proposed that phenolic antioxidants such as probucol exert their anti
      atherogenic effects through scavenging lipid-derived radicals. In this study the
      potential for genomics to reveal unanticipated pharmacological properties of
      phenolic antioxidants is explored. It was found that two anti-atherogenic
      compounds, BO-653 and probucol, inhibited the expression of three alpha-type
      proteasome subunits, PMSA2, PMSA3, and PMSA4 in human umbilical vein endothelial
      cells. Here we report that both BO-653 and probucol caused not only inhibition of
      the mRNA levels of these three subunits but also inhibition of both the gene
      expression and protein synthesis of the alpha-type subunit, PMSA1. Other subunit
      components of the proteasome such as the beta-type subunits (PMSB1, PMSB7), the
      ATPase subunit of 19 S (PMSC6), the non-ATPase subunit of 19 S (PMSD1), and PA28
      (PMSE2) were not significantly affected by treatment with these compounds. The
      specific inhibition of alpha-type subunit expression in response to these
      antioxidants resulted in functional alterations of the proteasome with
      suppression of degradation of multiubiquitinated proteins and IkappaBalpha. These
      results suggest that certain compounds previously classified solely as
      antioxidants are able to exert potentially important modulatory effects on
      proteasome function.

PMID- 11533054
TI  - The autoimmune regulator (AIRE) is a DNA-binding protein.
AB  - The autoimmune regulator (AIRE) protein is a putative transcription regulator
      with two plant homeodomain-type zinc fingers, a putative DNA-binding domain
      (SAND), and four nuclear receptor binding LXXLL motifs. We have shown here that
      in vitro, recombinant AIRE can form homodimers and homotetramers that were also
      detected in thymic protein extracts. Recombinant AIRE also oligomerizes
      spontaneously upon phosphorylation by cAMP dependent protein kinase A or protein
      kinase C. Similarly, thymic AIRE protein is phosphorylated at the tyrosine and
      serine/threonine residues. AIRE dimers and tetramers, but not the monomers, can
      bind to G-doublets with the ATTGGTTA motif and the TTATTA-box. Competition assays
      revealed that sequences with one TTATTA motif and two tandem repeats of ATTGGTTA
      had the highest binding affinity. These findings demonstrate that AIRE is an
      important DNA binding molecule involved in immune regulation.

PMID- 11533055
TI  - Chemoattractant-stimulated NF-kappaB activation is dependent on the low molecular
      weight GTPase RhoA.
AB  - Chemoattractants bind to seven transmembrane-spanning, G-protein-coupled
      receptors on monocytes and neutrophils and induce a variety of functional
      responses, including activation of the transcription factor NF-kappaB. The
      signaling mechanisms utilized by chemoattractants to activate NF-kappaB in human
      peripheral blood monocytes are poorly defined. We previously demonstrated that
      fMet-Leu-Phe (fMLP) stimulates NF-kappaB activation, and this function of fMLP
      requires phosphatidylinositol 3-kinase (PI3K). Here we present evidence that fMLP
      activates RhoA and that fMLP-induced NF-kappaB activation requires this small
      GTPase. Stimulation of monocytes with fMLP rapidly activated RhoA as well as NF
      kappaB, and their activation was markedly reduced by pertussis toxin treatment.
      Pretreatment of monocyte with a RhoA inhibitor, C3 transferase from Clostridium
      botulinum, effectively blocked fMLP-induced NF-kappaB activation as well as
      interleukin-1beta gene expression. A dominant negative form of RhoA (T19N) also
      inhibited fMLP-stimulated reporter gene expression in a kappaB-dependent manner.
      Cotransfection of the monocytic THP1 cells with a constitutively active form of
      RhoA (Q63L) with the promoter reporter plasmid results in a marked increase in NF
      kappaB-mediated reporter gene expression. Furthermore, the PI3K inhibitors
      wortmannin and LY294002 block RhoA activation induced by fMLP. These results
      demonstrate that low molecular weight GTPase RhoA is a novel signal transducer
      for fMLP-induced NF-kappaB activation and Galpha(i) or Galpha(o) class of
      heterotrimeric G proteins likely mediate RhoA activation via PI3K in human
      peripheral blood monocytes.

PMID- 11533056
TI  - Receptor number and caveolar co-localization determine receptor coupling
      efficiency to adenylyl cyclase.
AB  - Recent evidence suggests that many signaling molecules localize in microdomains
      of the plasma membrane, particularly caveolae. In this study, overexpression of
      adenylyl cyclase was used as a functional probe of G protein-coupled receptor
      (GPCR) compartmentation. We found that three endogenous receptors in neonatal rat
      cardiomyocytes couple with different levels of efficiency to the activation of
      adenylyl cyclase type 6 (AC6), which localizes to caveolin-rich membrane
      fractions. Overexpression of AC6 enhanced the maximal cAMP response to beta(1)
      adrenergic receptor (beta(1)AR)-selective activation 3.7-fold, to beta(2)AR
      selective activation only 1.6-fold and to prostaglandin E(2) (PGE(2)) not at all.
      Therefore, the rank order of efficacy in coupling to AC6 is beta(1)AR > beta(2)AR
      > prostaglandin E(2) receptor (EP(2)R). beta(2)AR coupling efficiency was greater
      when we overexpressed the receptor or blocked its desensitization by expressing
      betaARKct, an inhibitor of G protein-coupled receptor kinase activation, but was
      not significantly greater when cells were treated with pertussis toxin.
      Assessment of receptor and AC expression indicated co-localization of AC5/6,
      beta(1)AR, and beta(2)AR, but not EP(2)R, in caveolin-rich membranes and caveolin
      3 immunoprecipitates, likely explaining the observed activation of AC6 by betaAR
      subtypes but lack thereof by PGE(2). When cardiomyocytes were stimulated with a
      betaAR agonist, beta(2)AR were no longer found in caveolin-3 immunoprecipitates;
      an effect that was blocked by expression of betaARKct. Thus, agonist-induced
      translocation of beta(2)AR out of caveolae causes a sequestration of receptor
      from effector and likely contributes to the lower efficacy of beta(2)AR coupling
      to AC6 as compared with beta(1)AR, which do not similarly translocate. Therefore,
      spatial co-localization is a key determinant of efficiency of coupling by
      particular extracellular signals to activation of GPCR-linked effectors.

PMID- 11533057
TI  - Structural requirements and mechanism for heparin-induced activation of a
      recombinant mouse mast cell tryptase, mouse mast cell protease-6: formation of
      active tryptase monomers in the presence of low molecular weight heparin.
AB  - Mast cell tryptase is stored as an active tetramer in complex with heparin in
      mast cell secretory granules. Previously, we demonstrated the dependence on
      heparin for the activation/tetramer formation of a recombinant tryptase. Here we
      have investigated the structural requirements for this activation process. The
      ability of heparin-related saccharides to activate a recombinant murine tryptase,
      mouse mast cell protease-6 (mMCP-6), was strongly dependent on anionic charge
      density and size. The dose-response curve for heparin-induced mMCP-6 activation
      displayed a bell-shaped appearance, indicating that heparin acts by binding to
      more than one tryptase monomer simultaneously. The minimal heparin
      oligosaccharide required for binding to mMCP-6 was 8-10 saccharide units. Gel
      filtration analyses showed that such short oligosaccharides were unable to
      generate tryptase tetramers, but instead gave rise to active mMCP-6 monomers. The
      active monomers were inhibited by bovine pancreatic trypsin inhibitor, whereas
      the tetramers were resistant. Furthermore, monomeric (but not tetrameric) mMCP-6
      degraded fibronectin. Our results suggest a model for tryptase tetramer formation
      that involves bridging of tryptase monomers by heparin or other highly sulfated
      polysaccharides of sufficient chain length. Moreover, our results raise the
      possibility that some of the reported activities of tryptase may be related to
      active tryptase monomers that may be formed according to the mechanism described
      here.

PMID- 11533058
TI  - MARCKS protein is a key molecule regulating mucin secretion by human airway
      epithelial cells in vitro.
AB  - Hypersecretion of airway mucin characterizes numerous respiratory diseases.
      Although diverse pathological stimuli can provoke exocytotic release of mucin
      from secretory cells of the airway epithelium, mechanisms involved remain
      obscure. This report describes a new paradigm for the intracellular signaling
      mechanism regulating airway mucin secretion. Direct evidence is provided that the
      myristoylated alanine-rich C kinase substrate (MARCKS) is a central regulatory
      molecule linking secretagogue stimulation at the cell surface to mucin granule
      release by differentiated normal human bronchial epithelial cells in vitro. Down
      regulation of MARCKS expression or disruption of MARCKS function in these cells
      inhibits the secretory response to subsequent stimulation. The intracellular
      mechanism controlling this secretory process involves cooperative action of two
      separate protein kinases, protein kinase C and cGMP-dependent protein kinase.
      Upon stimulation, activated protein kinase C phosphorylates MARCKS, causing
      translocation of MARCKS from the plasma membrane to the cytoplasm, where it is
      then dephosphorylated by a protein phosphatase 2A that is activated by cGMP
      dependent protein kinase, and associates with both actin and myosin.
      Dephosphorylated cytoplasmic MARCKS would also be free to interact with mucin
      granule membranes and thus could link granules to the contractile cytoskeleton,
      mediating their movement to the cell periphery and subsequent exocytosis. These
      findings suggest several novel intracellular targets for pharmacological
      intervention in disorders involving aberrant secretion of respiratory mucin and
      may relate to other lesions involving exocytosis of membrane-bound granules in
      various cells and tissues.

PMID- 11533059
TI  - RERG is a novel ras-related, estrogen-regulated and growth-inhibitory gene in
      breast cancer.
AB  - Using microarray analysis, we identified a unique ras superfamily gene, termed
      RERG (ras-related and estrogen-regulated growth inhibitor), whose expression was
      decreased or lost in a significant percentage of primary human breast tumors that
      show a poor clinical prognosis. Importantly, high RERG expression correlated with
      expression of a set of genes that define a breast tumor subtype that is estrogen
      receptor-positive and associated with a slow rate of tumor cell proliferation and
      a favorable prognosis for these cancer patients. RERG mRNA expression was induced
      rapidly in MCF-7 cells stimulated by beta-estradiol and repressed by tamoxifen
      treatment. Like Ras, RERG protein exhibited intrinsic GDP/GTP binding and GTP
      hydrolysis activity. Unlike Ras proteins, RERG lacks a known recognition signal
      for COOH-terminal prenylation and was localized primarily in the cytoplasm.
      Expression of RERG protein in MCF-7 breast carcinoma cells resulted in a
      significant inhibition of both anchorage-dependent and anchorage-independent
      growth in vitro and inhibited tumor formation in nude mice. These features of
      RERG are strikingly different from most Ras superfamily GTP-binding pro-teins and
      suggest that the loss of RERG expression may contribute to breast tumorigenesis.

PMID- 11533060
TI  - Comparison of isocitrate dehydrogenase from three hyperthermophiles reveals
      differences in thermostability, cofactor specificity, oligomeric state, and
      phylogenetic affiliation.
AB  - With the aim of gaining insight into the molecular and phylogenetic relationships
      of isocitrate dehydrogenase (IDH) from hyperthermophiles, we carried out a
      comparative study of putative IDHs identified in the genomes of the eubacterium
      Thermotoga maritima and the archaea Aeropyrum pernix and Pyrococcus furiosus. An
      optimum for activity at 90 degrees C or above was found for each IDH. PfIDH and
      ApIDH were the most thermostable with a melting temperature of 103.7 and 109.9
      degrees C, respectively, compared with 98.3 and 98.5 degrees C for TmIDH and
      AfIDH, respectively. Analytical ultracentrifugation revealed a tetrameric
      oligomeric state for TmIDH and a homodimeric state for ApIDH and PfIDH. TmIDH and
      ApIDH were NADP-dependent (K(m)((NADP)) of 55.2 and 44.4 microm, respectively)
      whereas PfIDH was NAD-dependent (K(m)((NAD)) of 68.3 microm). These data document
      that TmIDH represents a novel tetrameric NADP-dependent form of IDH and that
      PfIDH is a homodimeric NAD-dependent IDH not previously found among the archaea.
      The homodimeric NADP-IDH present in A. pernix is the most common form of IDH
      known so far. The evolutionary relationships of ApIDH, PfIDH, and TmIDH with all
      of the available amino acid sequences of di- and multimeric IDHs are described
      and discussed.

PMID- 11533061
TI  - Characterization of EHD4, an EH domain-containing protein expressed in the
      extracellular matrix.
AB  - To identify proteins that promote assembly of type VI collagen tetramers or
      stabilize type VI collagen filaments, a two-hybrid screen of a human placenta
      library was used and a new extracellular protein discovered. The cDNA sequence of
      the new protein encodes 541 amino acid residues. This cDNA sequence is identical
      to EHD4, a recently described member of the EH domain family of proteins. Two
      mRNAs of 4.4 and 3.0 kilobases were present in human skin fibroblasts and most
      tissues tested but were most prevalent in the heart. The chromosomal localization
      of the gene for this new protein was determined to be at 15q14-q15. Three
      polyclonal peptide antibodies were made against synthetic EHD4 peptides. The
      affinity-purified antibodies were used in immunofluorescent staining of
      developing limbs and matrices produced by human skin fibroblasts and mouse NIH3T3
      fibroblasts in culture. Embryonic rat limb cartilage was strongly stained
      throughout development, and cultured fibroblasts deposited an extracellular
      filamentous network containing EHD4. In non-denaturing extracts of fetal bovine
      cartilage and in human skin fibroblast culture media, two components of
      approximately 220 and 158 kDa were observed, which, after reduction, migrated as
      a 56-kDa component on SDS-polyacrylamide gel electrophoresis. EHD4 is the first
      extracellular matrix protein described that contains an EH domain.

PMID- 11533062
TI  - Characterization of the B12- and iron-sulfur-containing reductive dehalogenase
      from Desulfitobacterium chlororespirans.
AB  - The United Nations and the U.S. Environmental Protection Agency have identified a
      variety of chlorinated aromatics that constitute a significant health and
      environmental risk as "priority organic pollutants," the so-called "dirty dozen."
      Microbes have evolved the ability to utilize chlorinated aromatics as terminal
      electron acceptors in an energy-generating process called dehalorespiration. In
      this process, a reductive dehalogenase (CprA), couples the oxidation of an
      electron donor to the reductive elimination of chloride. We have characterized
      the B12 and iron-sulfur cluster-containing 3-chloro-4-hydroxybenzoate reductive
      dehalogenase from Desulfitobacterium chlororespirans. By defining the substrate
      and inhibitor specificity for the dehalogenase, the enzyme was found to require
      an hydroxyl group ortho to the halide. Inhibition studies indicate that the
      hydroxyl group is required for substrate binding. The carboxyl group can be
      replaced by other functionalities, e.g. acetyl or halide groups, ortho or meta to
      the chloride to be eliminated. The purified D. chlororespirans enzyme could
      dechlorinate an hydroxylated PCB (3,3',5,5'-tetrachloro-4,4'-biphenyldiol) at a
      rate about 1% of that with 3-chloro-4-hydroxybenzoate. Solvent deuterium isotope
      effect studies indicate that transfer of a single proton is partially rate
      limiting in the dehalogenation reaction.

PMID- 11533063
TI  - Domain architecture of a high mobility group A-type bacterial transcriptional
      factor.
AB  - Myxococcus xanthus transcriptional factor CarD participates in carotenogenesis
      and fruiting body formation. It is the only reported prokaryotic protein having
      adjacent "AT-hook" DNA-binding and acidic regions characteristic of eukaryotic
      high mobility group A (HMGA) proteins. The latter are small, unstructured,
      nonhistone nuclear proteins that function as architectural factors to remodel DNA
      and chromatin structure and modulate various DNA binding activities. We find CarD
      to be predominantly dimeric with two stable domains: (a) an N-terminal domain of
      defined secondary and tertiary structure which is absent in eukaryotic HMGA
      proteins; (b) a C-terminal domain formed by the acidic and AT-hook segments and
      lacking defined structure. CarD, like HMGA proteins, binds specifically to the
      minor-groove of AT-rich DNA present in two appropriately spaced tracts. As in
      HMGA proteins, casein kinase II can phosphorylate the CarD acidic region, and
      this dramatically decreases the DNA binding affinity of CarD. The acidic region,
      in addition to modulating DNA binding, confers structural stability to CarD. We
      discuss how the structural and functional plasticity arising from domain
      organization in CarD could be linked to its role as a general transcriptional
      factor in M. xanthus.

PMID- 11533064
TI  - Inositol 1,3,4-trisphosphate 5/6-kinase is a protein kinase that phosphorylates
      the transcription factors c-Jun and ATF-2.
AB  - Phosphorylation of inositol 1,3,4-trisphosphate by inositol 1,3,4-trisphosphate
      5/6-kinase is the first committed step in the formation of higher phosphorylated
      forms of inositol. We have shown that the eight proteins called the COP9
      signalosome complex copurify with calf brain 5/6-kinase. Because the complex has
      been shown to phosphorylate c-Jun in vitro, we tested both the complex and 5/6
      kinase and found that both are able to phosphorylate c-Jun and ATF-2 on
      serine/threonine residues. These findings establish a link between two major
      signal transduction systems: the inositol phosphates and the stress response
      system.

PMID- 11533065
TI  - F-ATPase: forced full rotation of the rotor despite covalent cross-link with the
      stator.
AB  - In ATP synthase (F(O)F(1)-ATPase) ion flow through the membrane-intrinsic
      portion, F(O), drives the central "rotor", subunits c(10)epsilongamma, relative
      to the "stator" ab(2)delta(alphabeta)(3). This converts ADP and P(i) into ATP.
      Vice versa, ATP hydrolysis drives the rotation backwards. Covalent cross-links
      between rotor and stator subunits have been shown to inhibit these activities.
      Aiming at the rotary compliance of subunit gamma we introduced disulfide bridges
      between gamma (rotor) and alpha or beta (stator). We engineered cysteine residues
      into positions located roughly at the "top," "center," and "bottom" parts of the
      coiled-coil portion of gamma and suitable residues on alpha or beta. This part of
      gamma is located at the center of the (alphabeta)(3) domain with its C-terminal
      part at the top of F(1) and the bottom part close to the F(O) complex. Disulfide
      bridge formation under oxidizing conditions was quantitative as shown by SDS
      polyacrylamide gel electrophoresis and immunoblotting. As expected both the
      ATPase activities and the yield of rotating subunits gamma dropped to zero when
      the cross-link was formed at the center (gammaL262C <--> alphaA334C) and bottom
      (gammaCys(87) <--> betaD380C) positions. But much to our surprise disulfide
      bridging impaired neither ATP hydrolysis activity nor the full rotation of gamma
      and the enzyme-generated torque of oxidized F(1), which had been engineered at
      the top position (gammaA285C <--> alphaP280C). Apparently the high torque of this
      rotary engine uncoiled the alpha-helix and forced amino acids at the C-terminal
      portion of gamma into full rotation around their dihedral (Ramachandran) angles.
      This conclusion was supported by molecular dynamics simulations: If gammaCys(285)
      Val(286) are attached covalently to (alphabeta)(3) and gammaAla(1)-Ser(281) is
      forced to rotate, gammaGly(282)-Ala(284) can serve as cardan shaft.

PMID- 11533066
TI  - A secreted aminopeptidase of Pseudomonas aeruginosa. Identification, primary
      structure, and relationship to other aminopeptidases.
AB  - Using leucine-p-nitroanilide (Leu-pNA) as a substrate, we demonstrated
      aminopeptidase activity in the culture filtrates of several Pseudomonas
      aeruginosa strains. The aminopeptidase was partially purified by DEAE-cellulose
      chromatography and found to be heat stable. The apparent molecular mass of the
      enzyme was approximately 56 kDa; hence, it was designated AP(56). Heating (70
      degrees C) of the partially purified aminopeptidase preparations led to the
      conversion of AP(56) to a approximately 28-kDa protein (AP(28)) that retained
      enzyme activity, a reaction that depended on elastase (LasB). The pH optimum for
      Leu-pNA hydrolysis by AP(28) was 8.5. This activity was inhibited by Zn chelators
      but not by inhibitors of serine- or thiol-proteases, suggesting that AP(28) is a
      Zn-dependent enzyme. Of several amino acid p-nitroanilide derivatives examined,
      Leu-pNA was the preferred substrate. The sequences of the first 20 residues of
      AP(56) and AP(28) were determined. A search of the P. aeruginosa genomic data
      base revealed a perfect match of these sequences with positions 39-58 and 273
      291, respectively, in a 536-amino acid residue open reading frame predicted to
      encode an aminopeptidase. A search for sequence similarities with other proteins
      revealed 52% identity with Streptomyces griseus aminopeptidase, approximately 35%
      identity with Saccharomyces cerevisiae aminopeptidase Y and a hypothetical
      aminopeptidase from Bacillus subtilis, and 29-32% with Aeromonas caviae, Vibrio
      proteolyticus, and Vibrio cholerae aminopeptidases. The residues potentially
      involved in zinc coordination were conserved in all these proteins. Thus, P.
      aeruginosa aminopeptidase may belong to the same family (M28) of
      metalloproteases.

PMID- 11533067
TI  - Serum amyloid P component is the Shiga toxin 2-neutralizing factor in human
      blood.
AB  - It has been suggested that some factor present in human plasma binds to Shiga
      toxin 2 (Stx2) and neutralizes it in vitro (Bitzan, M., Klemt, M., Steffens, R.,
      and Muller-Wiefel, D. E. (1993) Infection 21, 140-145). This factor does not
      exist in other species (Caprioli, A., Luzzi, I., Seganti, L., Marchetti, M.,
      Karmali, M., Clarke, I., and Boyd, B. (1994) Recent Adv. VTEC Infect. 353-356).
      Because analysis of this factor is important to understanding the pathology
      induced by Shiga toxin-producing Escherichia coli, we purified this factor from
      human plasma and identified it. Purification was carried out by serially
      subjecting human plasma to Con A-Sepharose, DEAE-Sepharose, hydroxyapatite, and
      gel-filtration high performance liquid chromatography (HPLC), using Stx2
      neutralizing activity as the indicator. The gel-filtration HPLC fraction yielded
      a single band on SDS-polyacrylamide gel electrophoresis. Twenty N-terminal amino
      acid residues of this fraction were analyzed and found to correspond perfectly to
      human serum amyloid P component (HuSAP). Because commercially available HuSAP
      also showed Stx2 binding and neutralizing activity, we identified this factor as
      HuSAP.

PMID- 11533068
TI  - Bone marrow aspiration.
AB  - Bone marrow aspiration biopsies are carried out principally to permit cytological
      assessment but also for immunophenotypic, cytogenetic, molecular genetic, and
      other specialised investigations. Often, a trephine biopsy is carried out as part
      of the same procedure. Bone marrow aspirations should be carried out by trained
      individuals who are aware of the indications, contraindications, and hazards of
      the procedure. They should follow a standard operating procedure. The operator
      should have made an adequate assessment of clinical and haematological features
      to ensure both that appropriate indications exist and that all relevant tests are
      performed. For the patient's comfort and safety, the posterior iliac crest is
      generally the preferred site of aspiration. Films of aspirated marrow and, when
      appropriate, films of crushed particles should be made and labelled. Once
      thoroughly dry, films should be fixed and stained. As a minimum, a Romanowsky
      stain and a Perls' stain are required. A cover slip should be applied. The bone
      marrow films should be assessed and reported in a systematic manner so that
      nothing of importance is overlooked, using a low power, then intermediate, then
      high power objective. A differential count should be performed. An interpretation
      of the findings, in the light of the clinical and haematological features, should
      be given. The report should be signed or computer authorised, using a secure
      password, and issued in a timely manner.

PMID- 11533069
TI  - D-dimer testing: the role of the clinical laboratory in the diagnosis of
      pulmonary embolism.
AB  - Pulmonary embolism is a common, yet often unsuspected and unrecognised disease
      associated with a high mortality. New, objective, "user friendly" and cost
      effective diagnostic strategies are being explored. D-dimers, the fibrinolytic
      degradation products of crosslinked fibrin, have emerged as the most useful of
      the procoagulant activity and ongoing fibrinolysis markers. D-dimer measurements
      are very sensitive in excluding a diagnosis of pulmonary embolism in the setting
      of normal values, a low clinical suspicion, and non-diagnostic lung scans.
      Several assays have been developed and are reviewed.

PMID- 11533071
TI  - Current problems in the development of specific immunotherapeutic approaches to
      cancer.

PMID- 11533070
TI  - Immune responses to tumour antigens: implications for antigen specific
      immunotherapy of cancer.
AB  - Tumour associated antigens recognised by cellular or humoral effectors of the
      immune system are potential targets for antigen specific cancer immunotherapy.
      Different categories of cancer antigens have been identified that induce
      cytotoxic T lymphocyte (CTL) responses in vitro and in vivo, namely: (1) "cancer
      testis" (CT) antigens, expressed in different tumours and normal testis, (2)
      melanocyte differentiation antigens, (3) point mutations of normal genes, (4)
      self antigens that are overexpressed in malignant tissues, and (5) viral
      antigens. Clinical studies with peptides and proteins derived from these antigens
      have been initiated to study the efficacy of inducing specific CTL responses in
      vivo. Immunological and clinical parameters for the assessment of antigen
      specific immune responses have been defined-delayed type hypersensitivity (DTH),
      CTL, autoimmmune, and tumour regression responses. Specific DTH and CTL responses
      and tumour regression have been observed after the intradermal administration of
      tumour associated peptides alone. Peptide specific immune reactions were enhanced
      after using granulocyte macrophage stimulating factor (GM-CSF) as a systemic
      adjuvant by increasing the frequency of dermal antigen presenting Langerhans
      cells. Complete tumour regression has been observed in the context of measurable
      peptide specific CTL. However, in single cases with disease progression after an
      initial tumour response, either a loss of single antigens targeted by CTL or of
      the presenting major histocompatibility complex (MHC) class I allele was
      detected, pointing towards immunisation induced immune escape. Cytokines to
      modulate antigen and MHC class I expression in vivo are being evaluated to
      prevent immunoselection. Recently, a new CT antigen, NY-ESO-1, has been
      identified on the basis of spontaneous antibody responses to tumour associated
      antigens. NY-ESO-1 appears to be one of the most immunogenic antigens known to
      date, with spontaneous immune responses observed in 50% of patients with NY-ESO-1
      expressing cancers. Clinical studies have been initiated to evaluate the
      immunogenicity of different NY-ESO-1 constructs to induce both humoral and
      cellular immune responses in vivo.

PMID- 11533072
TI  - Whither smooth muscle antibodies in the third millennium?

PMID- 11533073
TI  - Gastric intestinal metaplasia: subtypes and natural history.
AB  - BACKGROUND: It has been suggested that the subtyping of intestinal metaplasia in
      the stomach is useful in stratifying patients with regard to risk of developing
      gastric cancer. AIM: To determine whether subtyping intestinal metaplasia
      provided useful information regarding the natural history of intestinal
      metaplasia. METHODS: The study used large cup gastric biopsy specimens from
      predetermined locations (gastric mapping). Follow up biopsies were obtained at
      one, two, and/or nine years. Biopsies with intestinal metaplasia were stained
      with high iron diamine/Alcian blue (HID/AB) to determine whether they expressed
      neutral mucins, sialomucins, or sulphomucins. RESULTS: Seventy nine patients with
      intestinal metaplasia were studied and characterised with regard to the most
      advanced subtype of intestinal metaplasia. The most severe type of intestinal
      metaplasia was type II in 33 patients and type III in 34 patients. Helicobacter
      pylori was cured in 67 patients. Follow up showed that changes in type of
      metaplasia (apparent regression or progression) occurred in both directions and
      were independent of H pylori status. For example, biopsy sites with "loss" of
      metaplasia at a follow up visit might have it "reappear" at a subsequent visit.
      During follow up, no patient developed gastric dysplasia or died from gastric
      cancer. CONCLUSION: HID subtyping did not provide useful information to the
      clinician or the pathologist. The data are consistent with the notion that the
      pattern, extent, and severity of atrophy with/without intestinal metaplasia is a
      far more important predictor of increased cancer risk than intestinal metaplasia
      subtype.

PMID- 11533075
TI  - Loss of heterozygosity at cylindromatosis gene locus, CYLD, in sporadic skin
      adnexal tumours.
AB  - AIM: The gene for familial cylindromatosis (CYLD) has been localised to
      chromosome 16q, and has recently been cloned. Loss of heterozygosity (LOH) at 16q
      has also been demonstrated in sporadic cylindromas. The aim of this study was to
      investigate whether CYLD plays a role in the development of other skin appendage
      tumours. METHODS: A total of 55 cases of skin adnexal tumours, comprising 12
      different types, and a control group of 14 squamous cell carcinomas (SCCs) and
      basal cell carcinomas (BCCs) were studied. Three microsatellites (D16S407 (16p),
      D16S304 (16q), and D16S308 (16q)) were analysed for LOH after microdissection
      from paraffin wax embedded sections using laser capture microdissection. RESULTS:
      In keeping with previous data, a proportion of cylindromas exhibited LOH at
      markers on 16q, but not at 16p. The skin adnexal tumours showing a similar
      pattern included apocrine hydrocystomas, eccrine spiradenomas, and sebaceous
      adenoma. One case of syringoma showed LOH at 16q, and a further case at 16p, but
      not 16q. One case of eccrine hydrocystoma showed loss at 16p, but not 16q. The
      remaining tumours were either negative or non-informative. All tumours in the
      control group were either negative or non-informative, except for a single case
      of BCC showing LOH at 16q. CONCLUSION: CYLD may be involved in the development of
      skin adnexal tumours other than cylindromas.

PMID- 11533074
TI  - Immunohistochemical analysis of candidate gene product expression in the duodenal
      epithelium of children with coeliac sprue.
AB  - BACKGROUND: Coeliac sprue is a chronic disease, in which there is a
      characteristic mucosal lesion of the small intestine and impaired nutrient
      absorption, which improves upon the withdrawal of wheat gliadins and related
      grain proteins from the diet. Biopsy specimens demonstrate diffuse enteritis with
      pronounced atrophy or total loss of villi. There is also a long term risk of
      malignant disease. AIMS: To compare the immunoexpression of DCC (deleted in colon
      cancer), p53, E-cadherin, and beta-catenin in the duodenal mucosa of children
      with coeliac disease with that seen in children with no evidence of small
      intestinal disease. METHODS: To gain more insight into the genetic and
      immunohistochemical alterations of the duodenal epithelium in coeliac disease, 21
      endoscopic biopsies from children with coeliac disease and 10 duodenal biopsies
      from children without coeliac disease were immunohistochemically evaluated for
      p53, DCC, E-cadherin, and beta-catenin. RESULTS: DCC expression was not reduced
      in patients with coeliac disease compared with those without coeliac disease. p53
      positive nuclear immunostaining was seen in seven of the 21 patients with coeliac
      disease. Positive nuclear staining was seen mainly in the deep and the lateral
      aspects of the crypts. All patients in the control group were negative for p53.
      In nine and three of the 21 patients with coeliac disease, respectively, the
      immunohistochemical expression of E-cadherin and beta-catenin was reduced.
      However, both E-cadherin and beta-catenin immunostaining in the control group was
      not altered. CONCLUSIONS: E-cadherin and beta-catenin were reduced in the
      duodenal epithelium of children with coeliac disease when compared with normal
      mucosa. p53 was overexpressed in the duodenal mucosa of patients with coeliac
      disease. The reduced expression of E-cadherin and beta-catenin and p53
      overexpression may contribute to the morphological changes seen in the small
      intestinal mucosa in coeliac disease.

PMID- 11533076
TI  - Optimising testing for phospholipid antibodies.
AB  - AIM: To compare anticardiolipin (ACL) and anti-beta2 glycoprotein 1 (beta2gp1)
      enzyme linked immunosorbent assays (ELISAs) in the diagnosis of antiphospholipid
      syndrome (APS) and to incorporate these results into a meta-analysis of published
      data. METHOD: Three representative commercial ACL ELISAs and an in house beta2gp1
      assay were optimised and then assessed on 124 sera from normal donors, patients
      with infection, or patients with APS. A Medline search was screened for papers
      meeting defined criteria to conduct a meta-analysis. The performance of the
      assays used in this study was included. RESULTS: A non-quantitative ACL assay
      performed at least as well as the anti-beta2gp1 assay in the diagnosis of APS.
      Meta-analysis confirmed that neither assay is perfect, although the anti-beta2gp1
      assay had a higher specificity and lower sensitivity than the ACL assay.
      CONCLUSIONS: The pooled data suggest that the ACL assay is used to investigate
      thrombosis without overt underlying pathology and that the improved specificity
      of the anti-beta2gp1 assay is exploited where infection, connective tissue
      disease, or atheroma are present.

PMID- 11533077
TI  - Uncertainty in estimating blood ethanol concentrations by analysis of vitreous
      humour.
AB  - AIMS: To determine the concentrations of ethanol in femoral venous blood (FVB)
      and vitreous humour (VH) obtained during forensic necropsies. The ratios of
      ethanol concentrations in VH and FVB, the reference interval, and the associated
      confidence limits were calculated to provide information about the uncertainty in
      estimating FVB ethanol concentrations indirectly from that measured in VH.
      METHODS: Ethanol concentrations were determined in specimens of FVB and VH
      obtained from 706 forensic necropsies. The specimens were analysed in duplicate
      by headspace gas chromatography (HS-GC), with a precision (coefficient of
      variation) of 1.5% at a mean ethanol concentration of 500 mg/litre. The limit of
      detection of ethanol in body fluids by HS-GC in routine casework was 100
      mg/litre. RESULTS: In 34 instances, ethanol was present in VH at a mean
      concentration of 154 mg/litre, whereas the FVB ethanol concentration was reported
      as negative (< 100 mg/litre). These cases were excluded from the statistical
      analysis. The concentration of ethanol in FVB was higher than in VH in 93
      instances, with a mean difference of 160 mg/litre (range 0 to 900). The mean
      concentration of ethanol in FVB (n = 672) was 1340 mg/litre (SD, 990) compared
      with 1580 mg/litre (SD, 1190) in VH. The arithmetic mean VH/FVB ratio of ethanol
      was 1.19 (SD, 0.285) and the 95% range was 0.63 to 1.75. The mean and SD of the
      differences (log VH - log FVB) was 0.063 (SD, 0.109), which gives 95% limits of
      agreement (LOA) from -0.149 to 0.276. Transforming back to the original scale of
      measurement gives a geometric mean VH/FVB ratio of 1.16 and 95% LOA from 0.71 to
      1.89. These parametric estimates are in good agreement, with a median VH/FVB
      ratio of 1.18 and 2.5th and 97.5th centiles of 0.63 and 1.92. CONCLUSIONS: The
      ethanol distribution ratios (VH/FVB) show wide variation and this calls for
      caution when results of analysing VH at necropsy are used to estimate the
      concentration in FVB. Dividing the ethanol concentration in VH by 2.0 would
      provide a very conservative estimate of the ethanol content in FVB, being less
      than the true value, with a high degree of confidence.

PMID- 11533078
TI  - Association between TNF-alpha promoter polymorphism and Helicobacter pylori cagA
      subtype infection.
AB  - AIMS: To assess the importance of tumour necrosis factor alpha (TNF-alpha)
      promoter polymorphism in relation to infection with the cytotoxin associated gene
      A (cagA) subtype of Helicobacter pylori within a dyspeptic Korean population.
      METHODS: Eighty three patients with gastric disease and 113 healthy controls were
      studied. The DNA from gastric biopsy specimens was analysed by H pylori specific
      and cagA specific polymerase chain reaction (PCR). To characterise TNF-alpha
      polymorphism at positions -308 and -238, PCR based restriction fragment length
      polymorphism analysis was performed. RESULTS: Helicobacter pylori infection was
      closely correlated with G to A transition at position -308 of the TNF-alpha
      promoter when compared with healthy controls (odds ratio (OR), 2.912; 95%
      confidence interval (CI), 1.082 to 7.836; p = 0.034). Although TNF-alpha -308
      polymorphism in patients with H pylori was not significantly different from that
      in patients without H pylori, the -308A polymorphism was strongly associated with
      H pylori cagA subtype infection when compared with the polymorphism in cagA
      negative H pylori infection (OR, 8.757; 95% CI, 1.413 to 54.262; p = 0.019) and
      healthy controls (OR, 3.683; 95% CI, 1.343 to 10.101; p = 0.011). G to A genetic
      change at position -238 of the TNF-alpha gene was not significantly associated
      with H pylori cagA subtype infection. In addition, genetic polymorphisms at both
      sites of the TNF-alpha promoter in patients with H pylori infection did not
      correlate with the severity of disease. CONCLUSION: TNF-alpha -308A polymorphism
      was significantly related to infection with the H pylori cagA subtype in Korean
      patients with gastric disease.

PMID- 11533079
TI  - Adrenal lipomatous tumours: a 30 year clinicopathological experience at a single
      institution.
AB  - AIMS: Fatty tumours of the adrenal gland are uncommon and their features have
      received little attention in the literature. The aim of this study is to analyse
      the features of adrenal lipomatous tumours. METHODS: The histological features of
      primary adrenal tumours reported over a 30 year period (1970 to 1999) in Queen
      Mary Hospital, Hong Kong were reviewed and the clinicopathological features of
      adrenal lipomatous tumours were analysed. RESULTS: Adrenal lipomatous tumours
      were noted in 20 patients (12 men, eight women), and they accounted for 4.8% of
      the primary adrenal tumours reported. The adrenal fatty tumours comprised 11
      myelolipomas, three lipomas, three teratomas, two angiomyolipomas, and one
      liposarcoma. Calcification or bone was noted in one third (seven of 20) of the
      adrenal tumours. In some fatty tumours (myelolipoma and angiomyolipoma), the
      fatty component may be inconspicuous. This is the first report in the English
      literature of angiomyolipoma and liposarcoma of the adrenal gland. CONCLUSIONS:
      Different types of fatty tumours were noted in the adrenal gland. A high index of
      suspicion should be maintained with an aim of surgical treatment for selected
      patients with large and symptomatic adrenal lipomatous lesions. Histological
      confirmation is needed for diagnosis.

PMID- 11533080
TI  - Long term recovery of IgG and IgM production during HIV infection in a patient
      with common variable immunodeficiency (CVID).
AB  - AIMS: Common variable immunodeficiency (CVID) is the most common serious primary
      immunodeficiency. This paper describes the immunological consequences of human
      immunodeficiency virus (HIV) infection in a patient with familial CVID
      subsequently treated with highly active antiretroviral therapy (HAART). METHODS:
      Serial measurements over 11 years of serum immunoglobulins, specific antibodies
      to tetanus toxoid and pneumococcal polysaccharides, lymphocyte phenotypes, and
      HIV viral load were made. RESULTS: The patient recovered total serum IgG and IgM,
      but not IgA production, with adequate concentrations of specific antibodies,
      allowing withdrawal of intravenous immunoglobulin without an increase in
      infections. T cell numbers gradually declined and the patient developed a high
      grade B cell lymphoma. After successful chemotherapy, HAART was commenced, viral
      load fell from 472 000 to < 50 copies/ml, and CD4+ T cell numbers increased from
      13 to 661 x 10(6)/litre. Antibody production was maintained after suppression of
      viral load. CONCLUSIONS: This is the first definitive report of reversal of IgG
      and IgM deficiency in familial CVID after HIV infection. Failure to normalise IgA
      supports the concept of separate predisposing genetic factors for selective IgA
      deficiency, which when combined with others lead to CVID. Furthermore, a
      persistently high viraemia is not required to maintain the recovery of
      immunoglobulin values, suggesting this depends either on a transitory effect of a
      high viral load, or a persistence of low amounts of virus.

PMID- 11533081
TI  - Angiosarcoma arising from skeletal haemangiomatosis in an atomic bomb survivor.
AB  - The authors report a unique case in which an angiosarcoma arose from skeletal
      haemangiomatosis in a 72 year old man. This patient had a history of atomic bomb
      irradiation more than 50 years ago. Radiographically, the patient had multiple
      sclerotic foci of benign haemangiomas in the pelvis, the sacrum, and the left
      femur. The patient developed a high grade angiosarcoma in the left pubic bone. It
      is thought that atomic bomb irradiation played an important role in the
      development of the malignant lesion.

PMID- 11533082
TI  - Multifocal squamous cell carcinoma of the oesophagus following radiotherapy for
      bilateral breast carcinoma.
AB  - A 60 year old woman who presented with dysphagia and weight loss was found to
      have multiple foci of dysplasia and in situ and invasive squamous cell carcinoma
      scattered along the whole length of the oesophagus, with intervening areas of
      normal mucosa. The patient had a history of two breast carcinomas 19 and one year
      previously for which she had repeated radiotherapy. Several members of the
      patient's close family had histories of malignant disease. All oesophageal
      lesions and the more recent breast cancer showed positive immunostaining for p53
      protein. p53 mutations, some involving different exons, were also detected in
      these lesions. No p53 immunostaining or mutations were detected in the normal
      oesophageal mucosa. The findings suggest an independent origin of the multiple
      dysplastic and neoplastic foci, which might have developed in a background of a
      field change, possibly related to the previous radiotherapy. The strong family
      history of malignant diseases raises the possibility that, in addition, genetic
      factors might have played a role in the development of the oesophageal disease.

PMID- 11533083
TI  - Evidence of nerve sheath differentiation and high grade morphology in sclerosing
      epithelioid fibrosarcoma.
AB  - Sclerosing epithelioid fibrosarcoma is a recently described sarcoma in which
      ultrastructural evidence of fibroblastic differentiation forms part of the
      diagnostic criteria. This report describes a further case of this tumour, which
      showed evidence of both fibroblastic and perineurial differentiation by
      immunohistochemistry and electron microscopy, and which had areas of high grade
      morphology. The tumour metastasised and the patient died of disease 12 months
      after presentation. The relevance of these findings to diagnosis and
      differentiation in these tumours is discussed.

PMID- 11533084
TI  - Peripheral blood lymphocyte appearance in a case of I cell disease.
AB  - In general, peripheral blood smears are performed to obtain information with
      regard to various morphological features as an aid in the diagnosis of infection
      or malignancy. This report presents a patient with I cell disease (inclusion cell
      disease), a fatal lysosomal storage disorder caused by a defect in an enzyme
      responsible for the transfer of mannose-6-phosphate ligands to precursor
      lysosomal enzymes. As a consequence, most lysosomal enzymes are transported
      outside the cell instead of being correctly targeted into the lysosomes,
      resulting in the storage of macromolecules in lysosomes. I cell disease, with its
      heterogeneous clinical presentation, can be diagnosed by the presence of
      intracellular vacuole-like inclusions in lymphocytes and fibroblasts, high serum
      lysosomal enzyme activities, and a defect of N-acetylglucosamine-1
      phosphotransferase. This report describes the morphological aspects of peripheral
      lymphocytes in a blood smear of a patient, the first clue to the final diagnosis
      of I cell disease. The observed vacuole-like inclusions in lymphocytes of this
      patient were negative for periodic acid Schiff (PAS) and Sudan black B staining,
      in contrast to earlier reports.

PMID- 11533085
TI  - Merkel cell carcinoma can be distinguished from metastatic small cell carcinoma
      using antibodies to cytokeratin 20 and thyroid transcription factor 1.
AB  - AIM: To investigate whether immunohistochemical staining for cytokeratin 20
      (CK20) and thyroid transcription factor 1 (TTF-1) is useful in distinguishing
      Merkel cell carcinomas (MCCs) from metastatic small cell carcinomas (SCCs).
      METHODS: Eleven cases of MCC and 10 of lung SCC were stained for CK20 and TTF-1.
      RESULTS: Ten of 11 MCCs stained with the antibody to CK20. None was positive for
      TTF-1. No SCC stained with anti-CK20 and all stained strongly with anti-TTF-1.
      CONCLUSIONS: The use of both anti-CK20 and anti-TTF-1 can reliably distinguish
      between MCC and metastatic SCC, thus avoiding the need for a detailed clinical
      investigation of patients with MCC in whom metastatic SCC must be excluded.

PMID- 11533087
TI  - Formalin or not formalin; that is the question.

PMID- 11533086
TI  - Dual colour FISH in paraffin wax embedded bone trephines for identification of
      numerical and structural chromosomal abnormalities in acute myeloid leukaemia and
      myelodysplasia.
AB  - AIMS/BACKGROUND: The advent of new treatments for haematological malignancies has
      led to the need for a correlation between cytogenetic and morphological
      abnormalities. This study aimed to achieve this by the application of interphase
      cytogenetics to marrow trephine sections, a technique not previously reported for
      formalin fixed, paraffin wax embedded trephine biopsies. METHODS: Dual colour
      fluorescence in situ hybridisation (FISH) was used to detect numerical and
      structural abnormalities in routinely processed paraffin wax embedded trephine
      biopsies. Three cases with t(8;21) and three with t(15;17) were analysed,
      together with a case of trisomy 8. Chromosome specific probes were hybridised
      with sections and disclosed by fluorescein isothiocyanate and rhodamine/Texas red
      labelled antidigoxigenin and antibiotin amplification; translocations were
      identified by colocalisation of probes using a double wavelength bypass filter.
      RESULTS: A translocation signal was present in 12% and 11.5% of the cells counted
      in the t(8;21) and t(15;17) cases, respectively, but in none of the normal
      controls (p < 0.001). In the case of trisomy 8, 9% of the cells counted contained
      three hybridisation signals for chromosome 8, whereas no cell contained more than
      two in the normal control (p < 0.001). CONCLUSIONS: This technique is useful for
      archived routinely processed material, enabling it to be used as a research tool
      but also, and perhaps more importantly, in clinical practice.

PMID- 11533088
TI  - Acridine orange stain in the histological identification of Helicobacter pylori.

PMID- 11533089
TI  - Audit of colposcopy biopsy sectioning.

PMID- 11533090
TI  - Cytokeratin expression by CD34 positive blasts in a case of refractory anaemia
      with excess of blasts in transformation (RAEB-t).

PMID- 11533091
TI  - Adjuvant radiation therapy of rectal cancer.

PMID- 11533092
TI  - Who gets adjuvant treatment for stage II and III rectal cancer? Insight from
      surveillance, epidemiology, and end results--Medicare.
AB  - PURPOSE: To examine the relationship between patient characteristics and the use
      of adjuvant pelvic radiation with and without chemotherapy among patients aged 65
      years and older with stage II and III rectal cancer. PATIENTS AND METHODS: A
      retrospective cohort study using the Surveillance, Epidemiology, and End Results
      Medicare linked database identified 1,411 patients aged 65 and older with
      resected stage II and III rectal cancers diagnosed between 1992 and 1996. From
      claims submitted to Medicare, we measured the use of pelvic radiation therapy
      with or without chemotherapy and pre- or postoperatively. RESULTS: Fifty-seven
      percent of patients received radiation, 42% received chemotherapy and radiation,
      and 7% had treatment delivered preoperatively. Age was the strongest determinant
      of treatment: 73% of patients aged 65 to 69, 66% aged 70 to 75, 52% aged 75 to
      79, 39% aged 80 to 84, and 21% aged 85 to 89 received radiation. The age trend
      remained strong after adjusting for other factors that predict receipt of
      treatment and after exclusion of patients with any evident comorbidity (P <.001).
      Patients were more likely to receive radiation treatment if they had an abdominal
      perineal resection, stage III disease, or a T4 tumor. CONCLUSION: Because pelvic
      recurrences are a substantial cause of morbidity, further efforts are needed to
      ensure that elderly patients have the opportunity to make informed decisions
      regarding adjuvant treatment.

PMID- 11533093
TI  - Treatment with nephrectomy only for small, stage I/favorable histology Wilms'
      tumor: a report from the National Wilms' Tumor Study Group.
AB  - PURPOSE: Children younger than 24 months with small (< 550 g), favorable
      histology (FH) Wilms tumors (WTs) were shown in a pilot study to have an
      excellent prognosis when treated with nephrectomy only. PATIENTS AND METHODS: A
      study of nephrectomy only for the treatment of selected children with FH WT was
      undertaken. Stringent stopping rules were designed to insure closure of the study
      if the true 2-year relapse-free survival rate was 90% or lower. RESULTS: Seventy
      five previously untreated children younger than 24 months with stage I/FH WTs for
      which the surgical specimen weighed less than 550 g were treated with nephrectomy
      only. Three patients developed metachronous, contralateral WT 1.1, 1.4, and 2.3
      years after nephrectomy, and eight patients relapsed 0.3 to 1.05 years after
      diagnosis (median, 0.4 years; mean, 0.51 years). The sites of relapse were lung
      (n = 5) and operative bed (n = 3). The 2-year disease-free (relapse and
      metachronous contralateral WT) survival rate was 86.5%. The 2-year survival rate
      is 100% with a median follow-up of 2.84 years. The 2-year disease-free survival
      rate (excluding metachronous contralateral WT) was 89.2%, and the 2-year
      cumulative risk of metachronous contralateral WT was 3.1%. CONCLUSION: Children
      younger than 24 months treated with nephrectomy only for a stage I/FH WT that
      weighed less than 550 g had a risk of relapse, including the development of
      metachronous contralateral WT, of 13.5% 2 years after diagnosis. All patients who
      experienced relapse on this trial are alive at this time. This approach will be
      re-evaluated in a clinical trial using a less conservative stopping rule.

PMID- 11533094
TI  - Management of spontaneous rupture of hepatocellular carcinoma: single-center
      experience.
AB  - PURPOSE: To report the management of patients with spontaneous rupture of
      hepatocellular carcinoma (HCC) in a single center over a 10-year period and to
      evaluate a two-stage therapeutic approach. PATIENTS AND METHODS: A retrospective
      study was performed on all 1,716 patients with HCC who presented from 1989 to
      1998. The two-stage therapeutic approach to manage ruptured HCC consisted of
      initial management by conservative method, hemostasis by transarterial
      embolization (TAE) or surgical means, followed by second-stage hepatic resection
      or transarterial oily chemoembolization (TOCE). Results of definitive treatment
      were compared with patients with no history of rupture during the same study
      period. RESULTS: During the study period, 154 patients (9%) had spontaneous HCC
      rupture. Initial intervention to control bleeding included TAE in 42 patients,
      surgical hemostasis in 35 patients, and conservative management only in 53
      patients. The 30-day mortality rate was 38%. Independent factors on presentation
      affecting 30-day mortality were shock on admission, hemoglobin, serum total
      bilirubin, and known diagnosis of inoperable tumor. After initial stabilization
      and clinical evaluation, 33 patients underwent hepatic resection and 30 patients
      received TOCE. Median survival of the hepatectomy patients was 25.7 months; that
      of the TOCE patients was 9.7 months. Compared with patients with no rupture,
      survival after hepatectomy (25.7 months v 49.2 months, P =.003) was inferior but
      still substantially long, whereas survival after TOCE was comparable (9.7 months
      v 8.7 months, P =.904). CONCLUSION: Early mortality of spontaneous rupture of HCC
      was dependent on prerupture disease state, liver function, and severity of
      bleeding. Although it was a catastrophic presentation, prolonged survival could
      be achieved in selected patients with second-stage hepatic resection or TOCE.

PMID- 11533095
TI  - Body-surface area-based dosing does not increase accuracy of predicting cisplatin
      exposure.
AB  - PURPOSE: Most anticancer drugs are dosed based on body-surface area (BSA) to
      reduce interindividual variability of drug effects. We evaluated the relevance of
      this concept for cisplatin by analyzing cisplatin pharmacokinetics obtained in
      prospective studies in a large patient population. PATIENTS AND METHODS: Data
      were obtained from 268 adult patients (163 males/105 females; median age, 54
      years [range, 21 to 74 years]) with advanced solid tumors treated in phase I/II
      trials with cisplatin monotherapy or combination chemotherapy with etoposide,
      irinotecan, topotecan, or docetaxel. Cisplatin was administered either weekly (n
      = 93) or once every 3 weeks (n = 175) at dose levels of 50 to 100 mg/m(2) (3-hour
      infusion). Analysis of 485 complete courses was based on measurement of total and
      non-protein-bound cisplatin in plasma by atomic absorption spectrometry. RESULTS:
      No pharmacokinetic interaction was found between cisplatin and the anticancer
      drugs used in combination therapies. A linear correlation was observed between
      area under the curves of unbound and total cisplatin (r = 0.63). The mean plasma
      clearance of unbound cisplatin (CL(free)) was 57.1 +/- 14.7 L/h (range, 31.0 to
      116 L/h), with an interpatient variability of 25.6%. BSA varied between 1.43 and
      2.40 m(2) (mean, 1.86 +/- 0.19 m(2)), with an interpatient variability of 10.4%.
      When CL(free) was corrected for BSA, interindividual variability remained in the
      same order (23.6 v 25.6%). Only a weak correlation was found between CL(free) and
      BSA (r = 0.42). Intrapatient variability in CL(free), calculated from 90 patients
      was 12.1% +/- 7.8% (range, 0.30% to 32.7%). CONCLUSION: In view of the high
      interpatient variability in CL(free) relative to variation in observed BSA, no
      rationale for continuing BSA-based dosing was found. We recommend fixed-dosing
      regimens for cisplatin.

PMID- 11533096
TI  - Predictive impact of 2-18fluoro-2-deoxy-D-glucose positron emission tomography
      for residual postchemotherapy masses in patients with bulky seminoma.
AB  - PURPOSE: To establish the predictive potential of 2-18fluoro-2-deoxy-D-glucose
      positron emission tomography (FDG PET) for detecting viable tumor tissue in
      residual postchemotherapy masses of seminoma patients. PATIENTS AND METHODS: In
      this prospective multicenter trial, results of FDG PET studies in seminoma
      patients with postchemotherapy masses > or = 1 cm were correlated with either the
      histology of the resected lesion or the clinical outcome on follow-up without
      resection. Negative PET scans of residual lesions that were devoid of viable
      tumor tissue on resection or disappeared, shrunk, or remained stable in size for
      at least 2 years were rated as true-negative (TN). Positive scans without
      histologic or clinical evidence of tumor tissue were classified as false
      positive. In patients with histologically positive or progressive lesions,
      positive PET scans were defined as true-positive (TP) and negative scans, false
      negative (FN). RESULTS: Thirty-seven PET scans of 33 patients were assessable at
      a median follow-up time of 23 months (range, 2 to 46 months). Histologic data
      were available from nine patients who had undergone resection. Twenty-eight
      patients were followed-up clinically and radiologically. Twenty-eight scans were
      TN, eight were TP, and one was FN. All 14 residual lesions more than 3 cm and 22
      (96%) of the 23 < or = 3 cm were correctly predicted by FDG PET. The specificity
      (100%; 95% confidence interval [CI], 87.7% to 100%), sensitivity (89%; 95% CI,
      51.7% to 99.7%), positive predictive value (100%), and the negative predictive
      value (97%) of FDG PET were superior to data obtained by assessing residual tumor
      size (< or = or > 3 cm). CONCLUSION: FDG PET is a clinically useful predictor of
      viable tumor in postchemotherapy residuals of pure seminoma, especially those
      greater than 3 cm.

PMID- 11533097
TI  - Lymph node staging by positron emission tomography in patients with carcinoma of
      the cervix.
AB  - PURPOSE: The aim of this study was to compare the results of computed tomography
      (CT) and positron emission tomography (PET) with [18F]-fluoro-2-deoxy-D-glucose
      (FDG) for lymph node staging in patients with carcinoma of the cervix and to
      evaluate the relationship of the imaging findings to prognosis. PATIENTS AND
      METHODS: We retrospectively compared the results of CT lymph node staging and
      whole-body FDG-PET in 101 consecutive patients with carcinoma of the cervix.
      Patients were treated with standard irradiation and chemotherapy (as clinically
      indicated) and observed at 3-month intervals for a median of 15.4 months (range,
      2.5 to 30 months). Progression-free survival was evaluated by the Kaplan-Meier
      method. RESULTS: CT demonstrated abnormally enlarged pelvic lymph nodes in 20
      (20%) and para-aortic lymph nodes in seven (7%) of the 101 patients. PET
      demonstrated abnormal FDG uptake in pelvic lymph nodes in 67 (67%), in para
      aortic lymph nodes in 21 (21%), and in supraclavicular lymph node in eight (8%).
      The 2-year progression-free survival, based solely on para-aortic lymph node
      status, was 64% in CT-negative and PET-negative patients, 18% in CT-negative and
      PET-positive patients, and 14% in CT-positive and PET-positive patients (P
      <.0001). A multivariate analysis demonstrated that the most significant
      prognostic factor for progression-free survival was the presence of positive para
      aortic lymph nodes as detected by PET imaging (P =.025). CONCLUSION: This study
      demonstrates that FDG-PET detects abnormal lymph node regions more often than
      does CT and that the findings on PET are a better predictor of survival than
      those of CT in patients with carcinoma of the cervix.

PMID- 11533099
TI  - Using plasma transforming growth factor beta-1 during radiotherapy to select
      patients for dose escalation.
AB  - PURPOSE: The ability to prescribe treatment based on relative risks for normal
      tissue injury has important implications for oncologists. In non-small-cell lung
      cancer, increasing the dose of radiation may improve local control and survival.
      Changes in plasma transforming growth factor beta (TGFbeta) levels during
      radiotherapy (RT) may identify patients at low risk for complications in whom
      higher doses of radiation could be safely delivered. PATIENT AND METHODS:
      Patients with locally advanced or medically inoperable non-small-cell lung cancer
      received three-dimensional conformal RT to the primary tumor and radiographically
      involved nodes to a dose of 73.6 Gy (1.6 Gy twice daily). If the plasma TGFbeta
      level was normal after 73.6 Gy, additional twice daily RT was delivered to
      successively higher total doses. The maximum-tolerated dose was defined as the
      highest radiation dose at which < or = one grade 4 (life-threatening) late
      toxicity and < or = two grade 3 to 4 (severe life-threatening) late toxicities
      occurred. RESULTS: Thirty-eight patients were enrolled. Median follow-up was 16
      months. Twenty-four patients were not eligible for radiation dose escalation
      beyond 73.6 Gy because of persistently abnormal TGFbeta levels. Fourteen patients
      whose TGFbeta levels were normal after 73.6 Gy were escalated to 80 Gy (n = 8)
      and 86.4 Gy (n = 6). In the 86.4-Gy group, dose-limiting toxicity was reached
      because there were two (33%) grade 3 late toxicities. CONCLUSION: It is feasible
      to use plasma TGFbeta levels to select patients for RT dose escalation for non
      small-cell lung cancer. The maximum-tolerated dose using this approach is 86.4
      Gy.

PMID- 11533098
TI  - Quality-of-life outcomes after primary androgen deprivation therapy: results from
      the Prostate Cancer Outcomes Study.
AB  - PURPOSE: To compare health-related quality-of-life outcomes after primary
      androgen deprivation (AD) therapy with orchiectomy versus luteinizing hormone
      releasing hormone (LHRH) agonists for patients with prostate cancer. PATIENTS AND
      METHODS: Men (n = 431) newly diagnosed with all stages of prostate cancer from
      six geographic regions who participated in the Prostate Cancer Outcomes Study and
      who received primary AD therapy but no other treatments within 12 months of
      initial diagnosis were included in a study of health outcomes. Comparisons were
      statistically adjusted for patient sociodemographic and clinical characteristics,
      timing of therapy, and use of combined androgen blockade. RESULTS: More than half
      of the patients receiving primary AD therapy had been initially diagnosed with
      clinically localized prostate cancer. Among these patients, almost two thirds
      were at high risk of progression on the basis of prognostic factors. Sexual
      function outcomes were similar by treatment group both before and after
      implementation of AD therapy. LHRH patients reported more breast swelling than
      did orchiectomy patients (24.9% v 9.7%, P <.01). LHRH patients reported more
      physical discomfort and worry because of cancer or its treatment than did
      orchiectomy patients. LHRH patients assessed their overall health as fair or poor
      more frequently than did orchiectomy patients (35.4% v 28.1%, P =.01) and also
      were less likely to consider themselves free of prostate cancer after treatment.
      CONCLUSION: Most endocrine-related health outcomes are similar after surgical
      versus medical primary hormonal therapy. Stage at diagnosis had little effect on
      outcomes. These results provide representative information comparing surgical and
      medical AD therapy that may be used by physicians and patients to inform
      treatment decisions.

PMID- 11533100
TI  - Impact of high-dose chemotherapy on peripheral T-cell lymphomas.
AB  - PURPOSE: To evaluate the outcome of high-dose chemotherapy (HDCT) and autologous
      or allogeneic hematopoietic transplantation in patients with peripheral T-cell
      lymphoma (PTCL) who experienced disease recurrence after prior conventional
      chemotherapy. PATIENTS AND METHODS: We performed a retrospective analysis of 36
      PTCL patients from the University of Texas M.D. Anderson Cancer Center treated
      between 1989 and 1998 with HDCT and autologous or allogeneic hematopoietic
      transplantation. RESULTS: A total of 36 patients were studied (29 received
      autologous transplantation, and seven received allogeneic transplantation). The
      overall survival rate at 3 years was 36% (95% confidence interval [CI], 23% to
      59%), and the progression-free survival (PFS) rate was 28% (95% CI, 16% to 49%).
      The pretransplant serum lactate dehydrogenase level was the most important
      prognostic factor for both survival and PFS rates (P < .001). A Pretransplant
      International Prognostic Index score of < or = 1 indicated a superior survival
      rate (P = .036) but not an improved PFS rate. A median follow-up of 43 months
      (range, 13 to 126 months) showed 13 patients (36%) were still alive with no
      evidence of disease. CONCLUSION: Our results are comparable to the published data
      on HDCT in B-cell non-Hodgkin's lymphoma (NHL) patients despite the fact that
      patients with PTCL are known to have a worse outcome compared with B-cell NHL
      patients. Considering the dismal outcome of conventional chemotherapy in PTCL
      patients, these data suggest the hypothesis that the poor prognostic implication
      of T-cell phenotyping in NHL might be overcome by frontline HDCT and
      transplantation.

PMID- 11533102
TI  - Unusual presentations of thoracic tumors: Case 1. Acute adrenal insufficiency due
      to metastatic lung cancer.

PMID- 11533101
TI  - Purging of autologous peripheral-blood stem cells using CD34 selection does not
      improve overall or progression-free survival after high-dose chemotherapy for
      multiple myeloma: results of a multicenter randomized controlled trial.
AB  - PURPOSE: Although high-dose chemotherapy supported by autologous peripheral-blood
      progenitor-cell (PBPC) transplantation improves response rates and survival for
      patients with multiple myeloma, all patients eventually develop progressive
      disease after transplantation. It has been hypothesized that depletion of
      malignant plasma cells from autografts may improve outcome by reducing infused
      cells contributing to relapse. PATIENTS AND METHODS: A randomized phase III study
      using the CEPRATE SC System (Cellpro, Bothell, WA) to enrich CD34(+) autograft
      cells and passively purge malignant plasma cells was completed in 190 myeloma
      patients randomized to receive an autograft of CD34-selected or unselected PBPCs.
      RESULTS: After CD34 selection, tumor burden was reduced by 1.6 to 6.0 logs
      (median, 3.1), with 54% of CD34-enriched products having no detectable tumor.
      Median time to count recovery, number of transfusions, transplantation-related
      mortality, and days in hospital were equivalent between the two transplantation
      arms. With a median follow-up of 37 months, 33 patients (36%) in the selected and
      34 patients (35%) in the unselected arm had died (P =.784). Median overall
      survival in the selected arm was reached at 50 months and is not reached at this
      time in the unselected arm (P =.78). Median disease-free survival was 100 versus
      104 weeks (P =.82), with 67% of patients in the selected arm and 66% of patients
      in the unselected arm relapsing. CONCLUSION: This phase III trial demonstrates
      that although CD34 selection significantly reduces myeloma cell contamination in
      PBPC collections, no improvement in disease-free or overall survival was
      achieved.

PMID- 11533103
TI  - Unusual presentations of thoracic tumors: Case 2. Malignant mesothelioma
      mimicking rheumatoid pleurisy.

PMID- 11533104
TI  - Unusual presentations of thoracic tumors: Case 3. Parenchymal lipoma of the lung.

PMID- 11533105
TI  - Just whose autonomy is it?

PMID- 11533106
TI  - Classifying chronic myelomonocytic leukemia.

PMID- 11533107
TI  - Validation of the ucla integrated staging system for patients with renal cell
      carcinoma.

PMID- 11533108
TI  - Full-impact medicine.

PMID- 11533109
TI  - Rhabdomyolysis, when observed with high-dose interferon-alfa (HDI) therapy, does
      not always exclude resumption of HDI.

PMID- 11533110
TI  - Structure-function relationships of A-, F- and V-ATPases.
AB  - Ion-translocating ATPases, such as the F(1)F(o)-, V(1)V(o)- and archaeal A(1)A(o)
      enzymes, are essential cellular energy converters which transduce the chemical
      energy of ATP hydrolysis into transmembrane ionic electrochemical potential
      differences. Based on subunit composition and primary structures of the subunits,
      these types of ATPases are related through evolution; however, they differ with
      respect to function. Recent work has focused on the three-dimensional structural
      relationships of the major, nucleotide-binding subunits A and B of the A(1)/V(1)
      ATPases and the corresponding beta and alpha subunits of the F(1)-ATPase, and the
      location of the coupling subunits within the stalk that provide the physical
      linkage between the regions of ATP hydrolysis and ion transduction. This review
      focuses on the structural homologies and diversities of A(1)-, F(1)- and V(1)
      ATPases, in particular on significant differences between the stalk regions of
      these families of enzymes.

PMID- 11533111
TI  - The control of flight force by a flapping wing: lift and drag production.
AB  - We used a dynamically scaled mechanical model of the fruit fly Drosophila
      melanogaster to study how changes in wing kinematics influence the production of
      unsteady aerodynamic forces in insect flight. We examined 191 separate sets of
      kinematic patterns that differed with respect to stroke amplitude, angle of
      attack, flip timing, flip duration and the shape and magnitude of stroke
      deviation. Instantaneous aerodynamic forces were measured using a two-dimensional
      force sensor mounted at the base of the wing. The influence of unsteady
      rotational effects was assessed by comparing the time course of measured forces
      with that of corresponding translational quasi-steady estimates. For each
      pattern, we also calculated mean stroke-averaged values of the force coefficients
      and an estimate of profile power. The results of this analysis may be divided
      into four main points. (i) For a short, symmetrical wing flip, mean lift was
      optimized by a stroke amplitude of 180 degrees and an angle of attack of 50
      degrees. At all stroke amplitudes, mean drag increased monotonically with
      increasing angle of attack. Translational quasi-steady predictions better matched
      the measured values at high stroke amplitude than at low stroke amplitude. This
      discrepancy was due to the increasing importance of rotational mechanisms in
      kinematic patterns with low stroke amplitude. (ii) For a 180 degrees stroke
      amplitude and a 45 degrees angle of attack, lift was maximized by short-duration
      flips occurring just slightly in advance of stroke reversal. Symmetrical
      rotations produced similarly high performance. Wing rotation that occurred after
      stroke reversal, however, produced very low mean lift. (iii) The production of
      aerodynamic forces was sensitive to changes in the magnitude of the wing's
      deviation from the mean stroke plane (stroke deviation) as well as to the actual
      shape of the wing tip trajectory. However, in all examples, stroke deviation
      lowered aerodynamic performance relative to the no deviation case. This
      attenuation was due, in part, to a trade-off between lift and a radially directed
      component of total aerodynamic force. Thus, while we found no evidence that
      stroke deviation can augment lift, it nevertheless may be used to modulate forces
      on the two wings. Thus, insects might use such changes in wing kinematics during
      steering maneuvers to generate appropriate force moments. (iv) While quasi-steady
      estimates failed to capture the time course of measured lift for nearly all
      kinematic patterns, they did predict with reasonable accuracy stroke-averaged
      values for the mean lift coefficient. However, quasi-steady estimates grossly
      underestimated the magnitude of the mean drag coefficient under all conditions.
      This discrepancy was due to the contribution of rotational effects that steady
      state estimates do not capture. This result suggests that many prior estimates of
      mechanical power based on wing kinematics may have been grossly underestimated.

PMID- 11533112
TI  - The neuropeptide proctolin induces phosphorylation of a 30 kDa protein associated
      with the thin filament in crustacean muscle.
AB  - In the isopod Idotea emarginata, the neuropeptide proctolin is contained in a
      single pair of motoneurones located in pereion ganglion 4. The two neurones
      supply dorsal extensor muscle fibres of all segments. Proctolin (1 micromoll(-1))
      potentiates the amplitude of contractures of single extensor muscle fibres
      elicited by 10 mmoll(-1) caffeine. In western blots of myofibrillar proteins
      isolated from single muscle fibres and treated with an anti-phosphoserine
      antibody, a protein with an apparent molecular mass of 30 kDa was consistently
      found. The phosphorylation of this protein was significantly increased by
      treating the fibres with proctolin. After separation of myofibrillar filaments, a
      30 kDa protein was found only in the thin filament fraction. This protein is
      phosphorylated and detected by an antiserum against crustacean troponin I.

PMID- 11533113
TI  - Targeting of an expressed neurotoxin by its recombinant baculovirus.
AB  - AaIT, an insect-selective neurotoxic polypeptide derived from scorpion venom, has
      recently been used to engineer recombinant baculoviruses for insect pest control.
      Lepidopterous larvae infected with an AaIT-expressing baculovirus reveal symptoms
      of paralysis identical to those induced by injection of the native toxin.
      However, the paralyzed larvae treated by the recombinant virus possess an
      approximately 50-fold lower hemolymph toxin concentration than insects paralyzed
      by the native toxin. The mechanism of this potentiation effect was studied using
      immunocytochemistry, electrophysiology and toxicity assays. (i) Light microscopy,
      using peroxidase-conjugated antibodies, revealed the presence of toxin in virus
      susceptible tissues, including tracheal epithelia located close to the central
      nervous system and beyond its lamellar enveloping sheath. (ii) High-resolution
      immunogold electron microscopical cytochemistry clearly revealed the presence of
      recombinant AaIT toxin inside the thoracic and abdominal ganglia on neuronal cell
      bodies and axonal membranes. (iii) Ventral nerve cords dissected from silkworm
      larvae infected with the recombinant baculovirus exhibited a high degree of
      excitability, expressed as enhanced frequency and bursting mode of their
      spontaneous activity, when compared to nerve cords infected with the wild-type
      virus. We conclude that the recombinant-virus-infected tracheal epithelia,
      outbranching in the body of an infected insect, (i) locally supply a continuous,
      freshly produced toxin to its neuronal receptors and (ii) introduce the expressed
      toxin to the insect central nervous system, thus providing it with critical
      target sites that are inaccessible to the native toxin.

PMID- 11533114
TI  - THE effects of tonic lung inflation on ventilation in the American bullfrog Rana
      catesbeiana Shaw.
AB  - This study was designed to determine whether lung inflation stimulates or
      inhibits breathing in frogs by examining the effect of tonic lung inflation on
      the 'fictive' breathing pattern of decerebrate, unidirectionally ventilated
      bullfrogs. Neural discharge was monitored in the trigeminal nerve as an
      indication of the frequency and force of contraction of the buccal pump, and in
      the laryngeal branch of the vagus nerve as an indication of glottal opening, and
      hence fictive lung ventilation. Based on the temporal coordination of discharge
      in the trigeminal and vagus nerves during naturally occurring breaths it was
      possible to characterize the fictive breaths as inflation, deflation or balanced
      breaths. Increasing lung inflation increased absolute breathing frequency by
      reducing the duration of apnea between breaths and promoting a change in
      breathing pattern from no breathing to single breaths, breathing episodes and,
      finally, to continuous breathing. Associated with this was a decrease in the
      amplitude and area of the integrated trigeminal electroneurogram associated with
      the lung breaths, indicative of a reduction in the force of the buccal pump, and
      a shift in the timing of the trigeminal and vagal discharge, indicative of a
      shift from inflation to deflation breaths. Taken together the data suggest that
      lung deflation produces infrequent, large-amplitude inflation breaths or cycles,
      but that progressive lung inflation changes the breathing pattern to one of high
      frequency attempts to deflate the lungs that are largely passive, and accompanied
      by contractions of the buccal pump that are no larger than those associated with
      normal buccal oscillations.

PMID- 11533115
TI  - Calcification in the planula and polyp of the hydroid Hydractinia
      symbiolongicarpus (Cnidaria, Hydrozoa).
AB  - This study examines calcification in planulae and polyps of the hydroid
      Hydractinia symbiolongicarpus. We observed that established colonies produce a
      crystalline mat on their substratum and that crystals visible by polarized light
      microscopy occur in the vacuoles of the gastrodermal cells of both polyps and
      planulae. The crystalline mat was found by infrared spectroscopy to contain
      calcium carbonate in the form of aragonite. The composition of the vacuolar
      crystals and the cellular mechanisms for manufacturing them were explored by
      alteration of calcium levels in the environment and by the use of pharmacological
      agents (acetazolamide, caffeine, DIDS, diltiazem, nifedipine, procaine, Ruthenium
      Red, ryanodine and verapamil) that affect cellular uptake and transport of
      calcium and bicarbonate. The results indicated that the crystals in the vacuoles
      contained calcium carbonate. The gastrodermal cells are hypothesized to serve as
      a physiological sink for excess calcium that enters the organism during motility,
      secretion and metamorphosis of the planula, and to create a crystalline
      substratum for the colony of polyps.

PMID- 11533116
TI  - Rainbow trout glucose transporter (OnmyGLUT1): functional assessment in Xenopus
      laevis oocytes and expression in fish embryos.
AB  - Recently, we reported the cloning of a putative glucose transporter (OnmyGLUT1)
      from rainbow trout embryos. In this paper, we describe the functional
      characteristics of OnmyGLUT1 and its expression during embryonic development of
      rainbow trout. Transport of D-glucose was analysed in Xenopus laevis oocytes
      following microinjection of mRNA transcribed in vitro. These experiments
      confirmed that OnmyGLUT1 is a facilitative Na(+)-independent transporter.
      Assessment of substrate selectivity, sensitivity to cytochalasin B and phloretin
      and kinetic parameters showed that the rainbow trout glucose transporter was
      similar to a carp transporter and to mammalian GLUT1. Embryonic expression of
      OnmyGLUT1 was studied using whole-mount in situ hybridization. Ubiquitous
      distribution of transcripts was observed until the early phase of somitogenesis.
      During the course of organogenesis, somitic expression decreased along the rostro
      caudal axis, finally ceasing in the mature somites. The OnmyGLUT1 transcripts
      were detected in the neural crest during the whole study period. Transcripts were
      also found in structures that are likely to originate from the neural crest cells
      (gill arches, pectoral fins, upper jaw, olfactory organs and primordia of mouth
      lips). Hexose transport activity was detected at all developmental stages after
      blastulation. Cytochalasin B blocked the accumulation of phosphorylated 2-deoxy-D
      glucose by dissociated embryonic cells, suggesting an important role for
      transport in glucose metabolism.

PMID- 11533117
TI  - Temperature interactions of the molecular chaperone Hsc70 from the eurythermal
      marine goby Gillichthys mirabilis.
AB  - Molecular chaperones participate in many aspects of protein biogenesis.
      Mechanistically, they recognize and bind to non-native proteins, prevent the
      aggregation of unfolded proteins and also, in some cases, facilitate refolding.
      Although a great deal is known about the cellular function of molecular
      chaperones in general, very little is known about the effect of temperature on
      molecular chaperones in non-model organisms, particularly in ectotherms that fold
      proteins under variable-temperature conditions in nature. To address this issue,
      we studied the temperature interactions of a major cytosolic molecular chaperone,
      Hsc70, from the eurythermal marine goby Gillichthys mirabilis. Using in vitro
      assays, we measured the intrinsic activity, unfolded-protein-stimulated activity,
      temperature sensitivity and heat stability of the ATPase activity of native Hsc70
      purified from G. mirabilis white muscle. Similar to other chaperones in the 70kDa
      heat-shock protein family, G. mirabilis Hsc70 exhibited a low intrinsic ATPase
      activity that was stimulated in vitro by the addition of unfolded protein. Across
      the environmentally relevant temperature range (10-35 degrees C), the ATPase
      activity of G. mirabilis Hsc70 displayed differential thermal sensitivity, with
      the greatest sensitivity occurring between 10 and 15 degrees C and the least
      sensitivity between 15 and 25 degrees C. In addition, the activity of Hsc70 was
      not significantly different between the unstimulated and unfolded-protein
      stimulated treatments, suggesting that the ATPase activity and the peptide
      binding domain of Hsc70 have similar thermal sensitivities in vitro. Finally, the
      thermal stability of Hsc70 ATPase activity greatly exceeded environmental
      temperatures for G. mirabilis, with activity up to 62.5 degrees C. Overall, the
      biochemical characterization of the ATPase activity suggests that, although Hsc70
      is not an extraordinarily thermally stable protein, it is capable of protein
      chaperoning cycles even at the extremes of environmental temperatures encountered
      by G. mirabilis in nature.

PMID- 11533118
TI  - A sport-physiological perspective on bird migration: evidence for flight-induced
      muscle damage.
AB  - Exercise-induced muscle damage is a well-described consequence of strenuous
      exercise, but its potential importance in the evolution of animal activity
      patterns is unknown. We used plasma creatine kinase (CK) activity as an indicator
      of muscle damage to investigate whether the high intensity, long-duration flights
      of two migratory shorebird species cause muscle damage that must be repaired
      during stopover. In two years of study, plasma CK activity was significantly
      higher in migrating western sandpipers (a non-synchronous, short-hop migrant),
      than in non-migrants. Similarly, in the bar-tailed godwit (a synchronous, long
      jump migrant), plasma CK activity was highest immediately after arrival from a
      4000-5000km flight from West Africa to The Netherlands, and declined before
      departure for the arctic breeding areas. Late-arriving godwits had higher plasma
      CK activity than birds that had been at the stopover site longer. Juvenile
      western sandpipers making their first southward migration had higher plasma CK
      activity than adults. These results indicate that muscle damage occurs during
      migration, and that it is exacerbated in young, relatively untrained birds.
      However, the magnitude of the increases in plasma CK activity associated with
      migratory flight were relatively small, suggesting that the level of muscle
      damage is moderate. Migrants may avoid damage behaviourally, or have efficient
      biochemical and physiological defences against muscle injury.

PMID- 11533119
TI  - Effects of sublethal ammonia exposure on swimming performance in rainbow trout
      (Oncorhynchus mykiss).
AB  - Adult trout Oncorhynchus mykiss fitted with a dorsal aortic catheter were exposed
      to 288+/-15 micromol l(-1) (mean +/- S.E.M.) total ammonia for 24h in water at a
      pH of 8.39+/-0.02, while swimming at a speed equivalent to 0.75 bodylengths s(-1)
      (BLs(-1)) in a Brett-type tunnel respirometer. The fish were then exposed to
      stepwise increments in swimming speed (0.25 BLs(-1) every 30 min) until
      exhaustion. Measurements of oxygen uptake (M(O2)) and plasma total ammonia levels
      and pH were made at each speed. Control trout were treated identically but
      without exposure to ammonia. Ammonia exposure caused an increase in plasma total
      ammonia level to 436+/-34 micromol l(-1), compared to 183+/-30 micromol l(-1)in
      control animals (N=6). A significant reduction in total plasma ammonia level was
      found in both groups during exercise, despite a large negative concentration
      gradient in those exposed to an elevated concentration of ammonia in water, which
      may indicate an active excretory process. The overall increase in plasma ammonia
      levels in exposed trout was associated with a significant reduction in critical
      swimming speed (U(crit)) to 1.61+/-0.17BL s(-1) from 2.23+/-0.15BL s(-1) in
      control animals. Ammonia-exposed trout had a significantly higher maintenance
      metabolic rate (MMR) than control fish, when estimated as the y-intercept of the
      relationship between swimming speed and M(O2). Active metabolic rate (AMR,
      maximum M(O2) as measured at U(crit)) was significantly lower in ammonia-exposed
      animals, leading to a profound reduction in factorial aerobic scope (AMR/MMR).
      Reduced U(crit) was also linked to a reduction in maximum tailbeat frequency.
      Calculation of membrane potentials (E(M)) in the white muscle of fish swum to
      U(crit) revealed a significant partial depolarisation of white muscle in ammonia
      exposed fish. This may have prevented white muscle recruitment and contributed to
      the reduced maximum tailbeat frequency and overall impairment of swimming
      performance in the ammonia-exposed fish.

PMID- 11533120
TI  - Mechanisms of urea tolerance in urea-adapted populations of Drosophila
      melanogaster.
AB  - When behavioral avoidance cannot prevent an animal from being exposed to novel
      environmental toxins, physiological mechanisms must cope with the toxin and its
      effects. We are investigating the basis of urea tolerance in populations of
      Drosophila melanogaster that have been selected to survive and develop in food
      containing 300 mmol l(-1) urea. Previous research has demonstrated that the urea
      selected larvae have lower levels of urea in their body than control larvae
      reared under the same conditions. The current series of experiments focuses on
      three possible ways of reducing urea levels in the body: urea metabolism,
      increased urea excretion and decreased urea uptake from the environment. We
      tested for urea metabolism directly, by assaying for activity of two urea
      metabolizing enzymes, and indirectly, by looking for reduced urea content of
      their medium. To measure urea excretion rates in whole animals, we reared control
      and urea-selected larvae on urea-containing food (urea food), switched them to
      normal food and monitored the loss of urea from their hemolymph. We measured urea
      uptake by rearing control and selected larvae on normal food, switching them to
      urea food and monitoring the rate of urea appearance in the hemolymph. We found
      no evidence for urea metabolism by either direct or indirect methods. Control
      larvae excreted urea at a higher rate than selected, probably because they
      contained more urea than the selected larvae and thus had a greater gradient for
      urea loss. The rate of urea uptake in selected larvae was 2 mmol l(-1) h(-1)
      slower than the rate in control larvae, a difference that could account for the
      measured differences in body urea levels. Thus the selected larvae appear to have
      adapted to urea exposure primarily by decreasing the ability of urea to enter
      their body in the first place. The mechanism responsible for this reduction in
      uptake is uncertain.

PMID- 11533121
TI  - Haemolymph sugar levels in foraging honeybees (Apis mellifera carnica):
      dependence on metabolic rate and in vivo measurement of maximal rates of
      trehalose synthesis.
AB  - Previous investigations of haemolymph sugar levels in honeybees have reported
      very different results, probably because different experimental conditions
      affected the activity levels of the animals. The present study investigated the
      dependence of haemolymph sugar levels in foraging honeybees on metabolic rate and
      whether the haemolymph sugar level is regulated. Free-flying foraging bees were
      trained to collect controlled amounts of sucrose solution of different
      concentrations (15%, 30% or 50% sucrose w/w). Immediately after feeding,
      metabolic rate was measured over a given time depending on the sucrose
      concentration, then crop-emptying rate and haemolymph sugar levels were measured.
      Bees exhibiting a wide range of metabolic rates were compared to establish
      whether the observed differences in haemolymph sugar levels were due to limits in
      the supply of sugars from the crop or in the rate of trehalose synthesis in the
      fat bodies. Independent of the concentration of the sucrose solution supplied,
      haemolymph trehalose, glucose and fructose levels were constant for metabolic
      rates from 0 to 4.5 ml CO(2)h(-1). At higher metabolic rates, trehalose
      concentration decreased while that of glucose and fructose increased, with the
      exception of bees fed 15% sucrose solution. As the supply of sugar from the crop
      via the proventriculus was sufficient to support even the highest metabolic
      rates, the observed pattern must result from an upper limit in the capacity of
      the fat body to synthesise trehalose. The maximal rate of conversion of glucose
      to trehalose in the fat body was therefore calculated to average 92.4 microg
      glucosemin(-1). However, for bees fed 15% sucrose solution both the rate of
      conversion of glucose to trehalose and the rate of sugar transport from the crop
      to the ventricle were limited, together resulting in a decrease in total
      haemolymph sugar levels for metabolic rates higher than 5 ml CO(2)h(-1).

PMID- 11533122
TI  - Hindlimb muscle function in relation to speed and gait: in vivo patterns of
      strain and activation in a hip and knee extensor of the rat (Rattus norvegicus).
AB  - Understanding how animals actually use their muscles during locomotion is an
      important goal in the fields of locomotor physiology and biomechanics. Active
      muscles in vivo can shorten, lengthen or remain isometric, and their mechanical
      performance depends on the relative magnitude and timing of these patterns of
      fascicle strain and activation. It has recently been suggested that terrestrial
      animals may conserve metabolic energy during locomotion by minimizing limb
      extensor muscle strain during stance, when the muscle is active, facilitating
      more economical force generation and elastic energy recovery from limb muscle
      tendon units. However, whereas the ankle extensors of running turkeys and hopping
      wallabies have been shown to generate force with little length change (<6%
      strain), similar muscles in cats appear to change length more substantially while
      active. Because previous work has tended to focus on the mechanical behavior of
      ankle extensors during animal movements, the actions of more proximal limb
      muscles are less well understood. To explore further the hypothesis of force
      economy and isometric behavior of limb muscles during terrestrial locomotion, we
      measured patterns of electromyographic (EMG) activity and fascicle strain (using
      sonomicrometry) in two of the largest muscles of the rat hindlimb, the biceps
      femoris (a hip extensor) and vastus lateralis (a knee extensor) during walking,
      trotting and galloping. Our results show that the biceps and vastus exhibit
      largely overlapping bursts of electrical activity during the stance phase of each
      step cycle in all gaits. During walking and trotting, this activity typically
      commences shortly before the hindlimb touches the ground, but during galloping
      the onset of activity depends on whether the limb is trailing (first limb down)
      or leading (second limb down), particularly in the vastus. In the trailing limb,
      the timing of the onset of vastus activity is slightly earlier than that observed
      during walking and trotting, but in the leading limb, this activity begins much
      later, well after the foot makes ground contact (mean 7% of the step cycle). In
      both muscles, EMG activity typically ceases approximately two-thirds of the way
      through the stance phase. While electrically active during stance, biceps
      fascicles shorten, although the extent of shortening differs significantly among
      gaits (P<0.01). Total average fascicle shortening strain in the biceps is greater
      during walking (23+/-3%) and trotting (27+/-5%) than during galloping (12+/-5%
      and 19+/-6% in the trailing and leading limbs, respectively). In contrast, vastus
      fascicles typically lengthen (by 8-16%, depending on gait) over the first half of
      stance, when the muscle is electrically active, before shortening slightly or
      remaining nearly isometric over much of the second half of stance. Interestingly,
      in the leading limb during galloping, vastus fascicles lengthen prior to muscle
      activation and exhibit substantial shortening (10+/-2%) during the period when
      EMG activity is recorded. Thus, patterns of muscle activation and/or muscle
      strain differ among gaits, between muscles and even within the same muscle of
      contralateral hindlimbs (as during galloping). In contrast to the minimal strain
      predicted by the force economy hypothesis, our results suggest that proximal limb
      muscles in rats operate over substantial length ranges during stance over various
      speeds and gaits and exhibit complex and changing activation and strain regimes,
      exemplifying the variable mechanical roles that muscles can play, even during
      level, steady-speed locomotion.

PMID- 11533123
TI  - Bursting properties of caudal neurosecretory cells in the flounder Platichthys
      flesus, in vitro.
AB  - Bursting activity in type 1 Dahlgren cells was studied using intra- and
      extracellular recording from an in vitro preparation of the caudal neurosecretory
      system of the euryhaline flounder. 45% of cells showed spontaneous bursts of
      approximately 120s duration and 380s cycle period. Similar bursts were triggered
      by short duration (<5s) depolarising or hyperpolarising pulses. Cells displayed a
      characteristic depolarising after potential, following either an action potential
      with associated afterhyperpolarisation, or a hyperpolarising current pulse. This
      depolarising after potential was related to a 'sag' potential, which developed
      during the hyperpolarising pulse. Both the depolarising after potential and the
      sag potential occurred only in cells at more depolarised (<60 mV) holding
      potentials. In addition, the amplitude of the depolarising after potential was
      dependent on the amplitude and the duration of the hyperpolarising pulse. The
      depolarising after potential following action potentials may provide a mechanism
      for facilitating repetitive firing during a burst. Extracellular recording
      revealed similar bursting in individual units which was not, however,
      synchronised between units. Spontaneous bursting activity recorded both intra-
      and extracellularly was inhibited by application of a known neuromodulator of the
      system, 5-hydroxytryptamine. This study provides a basis for investigating the
      relationship between physiological status, Dahlgren cell activity and
      neuropeptide secretion.

PMID- 11533124
TI  - Flight kinematics of the barn swallow (Hirundo rustica) over a wide range of
      speeds in a wind tunnel.
AB  - Two barn swallows (Hirundo rustica) flying in the Lund wind tunnel were filmed
      using synchronised high-speed cameras to obtain posterior, ventral and lateral
      views of the birds in horizontal flapping flight. We investigated wingbeat
      kinematics, body tilt angle, tail spread and angle of attack at speeds of 4-14
      ms(-1). Wingbeat frequency showed a clear U-shaped relationship with air speed
      with minima at 8.9 ms(-1)(bird 1) and 8.7 ms(-1) (bird 2). A method previously
      used by other authors of estimating the body drag coefficient (C(D,par)) by
      obtaining agreement between the calculated minimum power (V(min)) and the
      observed minimum wingbeat frequency does not appear to be valid in this species,
      possibly due to upstroke pauses that occur at intermediate and high speeds,
      causing the apparent wingbeat frequency to be lower. These upstroke pauses
      represent flap-gliding, which is possibly a way of adjusting the force generated
      to the requirements at medium and high speeds, similar to the flap-bound mode of
      flight in other species. Body tilt angle, tail spread and angle of attack all
      increase with decreasing speed, thereby providing an additional lift surface and
      suggesting an important aerodynamic function for the tail at low speeds in
      forward flight. Results from this study indicate the high plasticity in the
      wingbeat kinematics and use of the tail that birds have available to them in
      order to adjust the lift and power output required for flight.

PMID- 11533125
TI  - Glucose, exercise and insulin: emerging concepts.
AB  - Physical exercise induces a rapid increase in the rate of glucose uptake in the
      contracting skeletal muscles. The enhanced membrane glucose transport capacity is
      caused by a recruitment of glucose transporters (GLUT4) to the sarcolemma and t
      tubules. This review summarises the recent progress in the understanding of
      signals that trigger GLUT4 translocation in contracting muscle. The possible
      involvement of calcium, protein kinase C (PKC), nitric oxide (NO), glycogen and
      AMP-activated protein kinase (AMPK) are discussed. Furthermore, the possible
      mechanisms behind the well-described improvement of insulin action on glucose
      uptake and glycogen synthase activity in the post-exercise period is discussed.
      It is concluded that both during and following muscle contractions, glycogen
      emerges as an important modulator of signalling events in glucose metabolism.

PMID- 11533126
TI  - SK3 is an important component of K(+) channels mediating the
      afterhyperpolarization in cultured rat SCG neurones.
AB  - 1. Our aim was to identify the small-conductance Ca(2+)-activated K(+) channel(s)
      (SK) underlying the apamin-sensitive afterhyperpolarization (AHP) in rat superior
      cervical ganglion (SCG) neurones. 2. Degenerate oligonucleotide primers designed
      to the putative calmodulin-binding domain conserved in all mammalian SK channel
      sequences were employed to detect SK DNA in a cDNA library from rat SCG. Only a
      single band, corresponding to a fragment of the rSK3 gene, was amplified. 3.
      Northern blot analysis employing a PCR-generated rSK3 fragment showed the
      presence of mRNA coding for SK3 in SCG as well in other rat peripheral tissues
      including adrenal gland and liver. 4. The same rSK3 fragment enabled the
      isolation of a full-length rSK3 cDNA from the library. Its sequence was closely
      similar to, but not identical with, that of the previously reported rSK3 gene. 5.
      Expression of the rSK3 gene in mammalian cell lines (CHO, HEK cells) caused the
      appearance of a K(+) conductance with SK channel properties. 6. The application
      of selective SK blocking agents (including apamin, scyllatoxin and newer non
      peptidic compounds) showed these homomeric SK3 channels to have essentially the
      same pharmacological characteristics as the SCG afterhyperpolarization, but to
      differ from those of homomeric SK1 and SK2 channels. 7. Immunohistochemistry
      using a rSK3 antipeptide antibody revealed the presence of SK3 protein in the
      cell bodies and processes of cultured SCG neurones. 8. Taken together, these
      results identify SK3 as a major component of the SK channels responsible for the
      afterhyperpolarization of cultured rat SCG neurones.

PMID- 11533127
TI  - Differential regulation of G protein-gated inwardly rectifying K(+) channel
      kinetics by distinct domains of RGS8.
AB  - 1. The contribution of endogenous regulators of G protein signalling (RGS)
      proteins to G protein modulated inwardly rectifying K(+) channel (GIRK)
      activation/deactivation was examined by expressing mutants of Galpha(oA)
      insensitive to both pertussis toxin (PTX) and RGS proteins in rat sympathetic
      neurons. 2. GIRK channel modulation was reconstituted in PTX-treated rat
      sympathetic neurons following heterologous expression of G protein subunits.
      Under these conditions, noradrenaline-evoked GIRK channel currents displayed: (1)
      a prominent lag phase preceding activation, (2) retarded activation and
      deactivation kinetics, and (3) a lack of acute desensitization. 3. Unexpectedly,
      heterologous expression of RGS8 in neurons expressing PTX-i-RGS-insensitive
      Galpha(oA) shortened the lag phase and restored rapid activation, but retarded
      the deactivation phase further. These effects were found to arise from the N
      terminus, but not the core domain, of RGS8 thus suggesting actions on channel
      modulation independently of GTPase acceleration. 4. These findings indicate that
      different domains of RGS8 make distinct contributions to the temporal regulation
      of GIRK channels. The RGS8 core domain accelerates termination of the G-protein
      cycle presumably by increasing Galpha GTPase activity. In contrast, the N
      terminal domain of RGS8 appears to promote entry into the G protein cycle,
      possibly by enhancing coupling of receptors to the G protein heterotrimer.
      Together, these opposing effects should allow for an increase in temporal
      fidelity without a dramatic decrease in signal strength.

PMID- 11533128
TI  - Regulation of slowly activating potassium current (I(Ks)) by secretin in rat
      pancreatic acinar cells.
AB  - 1. The secretagogue-activated K(+) conductance is indispensable for the
      electrogenic Cl(-) secretion in exocrine tissue. In this study, we investigated
      the effect of secretin and other cAMP-mediated secretagogues on the slowly
      activating voltage-dependent K(+) current (I(Ks)) of rat pancreatic acinar cells
      (RPAs) with the whole-cell patch clamp technique. 2. Upon depolarization, RPAs
      showed I(Ks) superimposed upon the instantaneous background outward current.
      Secretin (5 nM), vasoactive intestinal peptide (5 nM), forskolin (5 microM),
      isoprenaline (10 microM) or 3-isobutyl-1-methylxanthine (IBMX, 0.1 mM) increased
      the amplitude of I(Ks) two- to fourfold. 3. The physiological concentration of
      secretin (50 pM) had a relatively weak effect on I(Ks) (160 % increase), which
      was significantly enhanced by transient co-stimulation with carbachol (CCh) (10
      microM). However, the secretin-induced production of cAMP, which was measured by
      enzyme-linked immunosorbent assay, was not augmented by co-stimulation with CCh.
      4. This study is the first to demonstrate the regulation of K(+) channels in RPAs
      by cAMP-mediated agonists. The I(Ks) channel is a common target for both Ca(2+)
      and cAMP agonists. The vagal stimulation under the physiological concentration of
      secretin facilitates I(Ks), which provides an additional driving force for Cl(-)
      secretion.

PMID- 11533129
TI  - Ammonium ions induce inactivation of Kir2.1 potassium channels expressed in
      Xenopus oocytes.
AB  - 1. The decay of inward currents was studied using the giant patch-clamp technique
      and a cloned inward rectifier K(+) channel, Kir2.1, expressed in Xenopus oocytes.
      2. In inside-out patches, inward currents carried by NH4(+) or Tl(+) decayed over
      time. When the voltage was more negative, the degree and rate of decay were
      greater. The rate of NH4(+)-induced decay saturated at a symmetrical [NH4(+)] of
      approximately 100 mM. The decay rate was slow (2.6 x 10(3) M(-1) s(-1)) at -140
      mV with 10 mM [NH4(+)]. 3. Upon a 10 degrees C increase in temperature, the
      single-channel NH4(+) current amplitude increased by a factor of 1.57, whereas
      the NH4(+)-induced decay rate increased by a factor of 2.76. In the R148Y Kir2.1
      mutant (tyrosine 148 is at the external pore mouth), NH4(+)-induced inactivation
      was no longer observed. 4. NH4(+) single-channel currents revealed one open and
      one closed state. The entry rate into the closed state was voltage dependent
      whereas the exit rate from the closed state was not. An increase of internal
      [NH4(+)] not only decreased the entry rate into but also elevated the exit rate
      from the closed state, consistent with the occupancy model modified from the foot
      in-the-door model of gating. 5. These results suggest that the decay of NH4(+)
      current is unlikely to be due to a simple bimolecular reaction leading to channel
      block. We propose that NH4(+) binding to Kir2.1 channels induces a conformational
      change followed by channel closure. 6. The decay induced by permeant ions other
      than K(+) may serve as a secondary selectivity filter, such that K(+) is the
      preferred permeant ion for Kir2.1 channels.

PMID- 11533130
TI  - Channel cytoplasmic loops alter voltage-dependent sodium channel activation in an
      isoform-specific manner.
AB  - 1. The isoform-specific functional role of cytoplasmic structures of two voltage
      gated sodium channel isoforms, the human cardiac channel (hH1) and the adult
      human skeletal muscle channel (hSkM1) was investigated through functional
      comparison of chimeras. 2. The voltage of half-activation (V(a)) for hH1 was
      shifted by > 20 mV in the hyperpolarised direction following internal papain
      treatment ('papain sensitive'), while V(a) for hSkM1 was unaffected ('papain
      insensitive'). 3. The hH1 region(s) responsible for this papain sensitivity was
      localised by testing a series of hH1/hSkM1 chimeras in which combinations of the
      large hH1 cytoplasmic loops joining the four transmembrane domains replaced
      analogous hSkM1 loops. Various chimeras were used to determine the smallest
      subset of loops that converted fully the papain-insensitive hSkM1 into a papain
      sensitive channel. Then three converse chimeras were tested in which hSkM1 loops
      replaced hH1 loops to determine the smallest subset of loops necessary and
      sufficient to convert the papain-sensitive hH1 into a papain-insensitive channel.
      4. Functional studies of this inclusive set of chimeras indicate that the first
      two cytoplasmic loops of the cardiac sodium channel that join domain I to II
      (loop A), and domain II to III (loop B), are both necessary, and together are
      sufficient to produce a papain-induced hyperpolarising shift in the voltage at
      which channels activate. When both loops are present (wild-type hH1 and the
      chimera hSkM1AB), V(a) for the channel shifts in the hyperpolarised direction by
      > 20 mV with papain treatment. When the analogous hSkM1 loops are present (wild
      type hSkM1 and the chimera hH1AB), V(a) for the channel is not sensitive to
      treatment with papain. For channels that contain only one of the two hH1 loops,
      the effect of papain on V(a) is intermediary. 5. Experiments performed in the
      absence of papain showed that the activation voltages of the double loop
      chimeras, hSkM1AB and hH1AB, were shifted significantly from V(a) for hSkM1 and
      V(a) for hH1, respectively, indicating that these loops directly alter channel
      activation voltage. The resulting shifts in V(a) were in opposing directions,
      suggesting that cytoplasmic control of activation voltage is isoform specific.
      V(a) for hSkM1AB was about 20 mV more depolarised than V(a) for hSkM1, and V(a)
      for hH1AB was about 9 mV more negative than V(a) for hH1. 6. These data are the
      first to indicate isoform-specific cytoplasmic regions of the voltage-gated
      sodium channel that directly and differently alter the voltage of channel
      activation.

PMID- 11533131
TI  - Muscarinic activation of inwardly rectifying K(+) conductance reduces EPSPs in
      rat hippocampal CA1 pyramidal cells.
AB  - 1. To determine how acetylcholine (ACh) modulates the somatodendritic processing
      of EPSPs, we performed whole-cell recordings from CA1 pyramidal cells of
      hippocampal slices and examined the effect of the cholinergic agonist, carbachol
      (CCh), on alpha-amino-3-hydroxy-5-methyl isoxazole-4-propionate (AMPA) EPSPs,
      miniature EPSPs, and EPSP-like waveforms evoked by brief dendritic glutamate
      pulses (glutamate-evoked postsynaptic potentials, GPSPs). 2. Although CCh is
      known to enhance the intrinsic excitability of the neuron in several ways,
      activation of atropine-sensitive (muscarinic) receptors on the apical dendrite or
      the soma of CA1 pyramidal cells consistently reduced the amplitude of EPSPs and
      GPSPs. 3. Cholinergic inhibition of evoked and simulated EPSP waveforms displayed
      considerable voltage dependence, with the amplitude of the postsynaptic
      potentials progressively declining with membrane hyperpolarization indicating the
      involvement of an inwardly rectifying current. 4. Extracellular Ba(2+) (200
      microM) and tertiapin (30 nM), a novel and selective blocker of G protein
      activated, inwardly rectifying K(+) (GIRK) channels, completely blocked the
      effect of CCh on GPSP amplitude. 5. Muscarinic reduction of GPSPs was not
      sensitive to the M1 receptor-preferring antagonist, pirenzepine, but was
      suppressed by the M2 receptor-preferring antagonist, methoctramine, and by the
      allosteric M2 receptor antagonist, gallamine. 6. In voltage-clamp recordings, CCh
      induced an ion current displaying inward rectification in the hyperpolarizing
      direction, which was identified as a GIRK current based on its sensitivity to low
      Ba(2+) and tertiapin. Its pharmacological profile paralleled that of the
      cholinergic GPSP reduction. 7. We link the observed reduction of postsynaptic
      potentials to the cholinergic activation of a GIRK conductance, which serves to
      partially shunt excitatory synaptic input.

PMID- 11533132
TI  - Cerebral functional anatomy of voluntary contractions of ankle muscles in man.
AB  - 1. Cerebral activation elicited by right-sided voluntary ankle muscle contraction
      was investigated by positron emission tomography measurements of regional
      cerebral blood flow. Two studies with eight subjects in each were carried out.
      Tonic isometric plantar and dorsiflexion and co-contraction of the antagonist
      muscles were investigated in study 1. Tonic contraction was compared with dynamic
      ramp-and-hold contractions in study 2. 2. All types of contraction elicited
      activation of the left primary motor cortex (M1). The distance between the M1
      peak activation locations for tonic isometric dorsi- and plantar flexion was 17
      mm. Co-contraction elicited activation of a larger area of M1 mainly located in
      between but partially overlapping the M1 areas activated during isolated dorsi
      /plantar flexion. 3. A voxel-by-voxel correlation analysis corrected for subject
      covariance showed for dorsiflexion a significant correlation between tibialis
      anterior EMG level and cerebral blood flow activation in the cerebellum and the
      M1 of the medial frontal cortex. For plantar flexion a significant correlation
      was found between soleus EMG and cerebral activation in the left medial S1 and
      M1, left thalamus and right cerebellum. 4. The activation during dynamic isotonic
      and isometric dorsi- and plantar flexion was significantly more extensive than
      during tonic contractions. In addition to M1, activation was seen in the
      contralateral supplementary motor area and bilaterally in the premotor and
      parietal cortices. Isotonic and isometric contractions did not differ except in a
      small area in the primary somatosensory cortex. 5. One possible explanation of
      the different cerebral activation during co-contraction compared to that during
      plantar/dorsiflexion is that slightly different populations of cortical neurones
      are involved. The more extensive activation during dynamic compared with tonic
      contractions may reflect a larger cortical drive necessary to initiate and
      accelerate movements.

PMID- 11533133
TI  - Heterologous expression of the Na(+),K(+)-ATPase gamma subunit in Xenopus oocytes
      induces an endogenous, voltage-gated large diameter pore.
AB  - 1. The gamma subunit is a specific component of the plasmalemmal Na(+),K(+)
      ATPase. Like structurally related single-spanning membrane proteins such as
      cardiac phospholemman, Mat-8 and renal CHIF, large ion conductances are activated
      when gamma subunits are expressed in Xenopus oocytes. 2. Here we report critical
      properties of the gamma-activated conductance. The gamma-activated conductance
      showed non-selective cationic and anionic permeation, and extremely slow
      kinetics, with an activation time constant > 1 s following steps to -100 mV. 3.
      The gamma-activated conductance was inhibited by extracellular divalent ions
      including Ba(2+) (K(i) = 0.7 mM) and Ca(2+) (K(i) = 0.4 mM). 4. 2-Deoxyglucose
      (MW approximately 180), inulin (MW approximately 5000) and spermidine (MW
      approximately 148) efflux could occur through the gamma-activated conductance
      pathway, indicating a large pore diameter. In contrast, dextran-70 (MW
      approximately 70 000) did not pass through the gamma-activated channel,
      indicating an upper limit to the pore size of approximately 50 A (5 nm). 5.
      Similar conductances that are permeable to large molecules were activated by
      extreme hyperpolarization (> -150 mV) of uninjected oocytes. 6. We conclude that
      the Na(+),K(+)-ATPase gamma subunits activate Ca(2+)- and voltage-gated, non
      selective, large diameter pores that are intrinsically present within the oocyte
      membrane.

PMID- 11533134
TI  - Mapping the urea channel through the rabbit Na(+)-glucose cotransporter SGLT1.
AB  - 1. The rabbit Na(+)-glucose cotransporter rbSGLT1 and its carboxy-terminal part,
      C5, which contains transmembrane helices 10-14 of SGLT1 and functions as a low
      affinity glucose uniporter, were expressed as individual proteins in Xenopus
      oocytes. Transport of 55 microM urea, ethylene glycol, mannitol and alpha-methyl
      D-glucopyranoside (alphaMDG) by control oocytes and by oocytes expressing SGLT1
      and C5 was studied by uptake measurements of the 14C-labelled substrates. 2.
      There was a 5- to 6-fold increase in urea transport mediated by C5, compared with
      control oocytes. Similar to SGLT1, the C5-urea uptake was cation independent,
      linear in time and with increasing urea concentration, and blocked with the same
      sensitivity by the inhibitor phloretin (K(i) approximately 1 mM). Like SGLT1 in
      choline buffer, the C5-mediated uptake was insensitive to phlorizin. 3. Mannitol
      was transported by C5 but not by SGLT1 or control oocytes. 4. The activation
      energy (E(a)) for urea transport through C5 was low (5 +/- 3 kcal mol(-1))
      compared with that of non-injected oocytes (16 +/- 0.5 kcal mol(-1)) and
      comparable with the E(a) of passive urea or water transport through intact SGLT1.
      5. The urea influx through C5 increased in the presence of alphaMDG, but not in
      the presence of the same concentration of mannitol. 6. We conclude that the five
      carboxy-terminal transmembrane helices of SGLT1 form a channel for the permeation
      of small molecules such as urea and water.

PMID- 11533135
TI  - Open probability of homomeric murine 5-HT3A serotonin receptors depends on
      subunit occupancy.
AB  - 1. The time course of macroscopic current responses of homomeric murine serotonin
      5-HT3A receptors was studied in whole cells and excised membrane patches under
      voltage clamp in response to rapid application of serotonin. 2. Serotonin
      activated whole cell currents with an EC(50) value for the peak response of 2
      microM and a Hill slope of 3.0 (n = 12), suggesting that the binding of at least
      three agonist molecules is required to open the channel. 3. Homomeric 5-HT3A
      receptors in excised membrane patches had a slow activation time course (mean +/-
      S.E.M. 10-90 % rise time 12.5 +/- 1.6 ms; n = 9 patches) for 100 microM
      serotonin. The apparent activation rate was estimated by fitting an exponential
      function to the rising phase of responses to supramaximal serotonin to be 136 s(
      1). 4. The 5-HT3A receptor response to 100 microM serotonin in outside-out
      patches (n = 19) and whole cells (n = 41) desensitized with a variable rate that
      accelerated throughout the experiment. The time course for desensitization was
      described by two exponential components (for patches tau(slow) 1006 +/- 139 ms,
      amplitude 31 %; tau(fast) 176 +/- 25 ms, amplitude 69 %). 5. Deactivation of the
      response following serotonin removal from excised membrane patches (n = 8) and
      whole cells (n = 29) was described by a dual exponential time course with time
      constants similar to those for desensitization (for patches tau(slow) 838 +/- 217
      ms, 55 % amplitude; tau(fast) 213 +/- 44 ms, 45 % amplitude). 6. In most patches
      (6 of 8), the deactivation time course in response to a brief 1-5 ms pulse of
      serotonin was similar to or slower than desensitization. This suggests that the
      continued presence of agonist can induce desensitization with a similar or more
      rapid time course than agonist unbinding. The difference between the time course
      for deactivation and desensitization was voltage independent over the range -100
      to -40 mV in patches (n = 4) and -100 to +50 mV in whole cells (n = 4),
      suggesting desensitization of these receptors in the presence of serotonin does
      not reflect a voltage-dependent block of the channel by agonist. 7.
      Simultaneously fitting the macroscopic 5-HT3A receptor responses in patches to
      submaximal (2 microM) and maximal (100 microM) concentrations of serotonin to a
      variety of state models suggests that homomeric 5-HT3A receptors require the
      binding of three agonists to open and possess a peak open probability greater
      than 0.8. Our modelling also suggests that channel open probability varies with
      the number of serotonin molecules bound to the receptor, with a reduced open
      probability for fully liganded receptors. Increasing the desensitization rate
      constants in this model can generate desensitization that is more rapid than
      deactivation, as observed in a subpopulation of our patches.

PMID- 11533136
TI  - Compartmental models of rat cerebellar Purkinje cells based on simultaneous
      somatic and dendritic patch-clamp recordings.
AB  - 1. Simultaneous dendritic and somatic patch-clamp recordings were made from
      Purkinje cells in cerebellar slices from 12- to 21-day-old rats. Voltage
      responses to current impulses injected via either the dendritic or the somatic
      pipette were obtained in the presence of the selective I(h) blocker ZD 7288 and
      blockers of spontaneous synaptic input. Neurons were filled with biocytin for
      subsequent morphological reconstruction. 2. Four neurons were reconstructed and
      converted into detailed compartmental models. The specific membrane capacitance
      (C(m)), specific membrane resistance (R(m)) and intracellular resistivity (R(i))
      were optimized by direct fitting of the model responses to the
      electrophysiological data from the same cell. Mean values were: C(m), 0.77 +/-
      0.17 microF cm(-2) (mean +/- S.D.; range, 0.64-1.00 microF cm(-2)), R(m), 122 +/-
      18 kOmega cm(2) (98-141 kOmega cm(2)) and R(i), 115 +/- 20 Omega cm (93-142 Omega
      cm). 3. The steady-state electrotonic architecture of these cells was compact
      under the experimental conditions used. However, somatic voltage-clamp recordings
      of parallel fibre and climbing fibre synaptic currents were substantially
      filtered and attenuated. 4. The detailed models were compared with a two
      compartment model of Purkinje cells. The range of synaptic current kinetics that
      can be faithfully recorded using somatic voltage clamp is predicted fairly well
      by the two-compartment model, even though some of its underlying assumptions are
      violated. 5. A model of I(h) was constructed based on voltage-clamp data, and
      inserted into the passive compartmental models. Somatic EPSP amplitude was
      substantially attenuated compared to the amplitude of dendritic EPSPs at their
      site of generation. However, synaptic efficacy of the same quantal synaptic
      conductance, as measured by the somatic EPSP amplitude, was only weakly dependent
      on synaptic location on spiny branchlets. 6. The passive electrotonic structure
      of Purkinje cells is unusual in that the steady-state architecture is very
      compact, while voltage transients such as synaptic potentials and action
      potentials are heavily filtered.

PMID- 11533137
TI  - Plasticity of rat central inhibitory synapses through GABA metabolism.
AB  - 1. The production of the central inhibitory transmitter GABA (gamma-aminobutyric
      acid) varies in response to different patterns of activity. It therefore seems
      possible that GABA metabolism can determine inhibitory synaptic strength and that
      presynaptic GABA content is a regulated parameter for synaptic plasticity. 2. We
      altered presynaptic GABA metabolism in cultured rat hippocampal slices using
      pharmacological tools. Degradation of GABA by GABA-transaminase (GABA-T) was
      blocked by gamma-vinyl-GABA (GVG) and synthesis of GABA through glutamate
      decarboxylase (GAD) was suppressed with 3-mercaptopropionic acid (MPA). We
      measured miniature GABAergic postsynaptic currents (mIPSCs) in CA3 pyramidal
      cells using the whole-cell patch clamp technique. 3. Elevated intra-synaptic GABA
      levels after block of GABA-T resulted in increased mIPSC amplitude and frequency.
      In addition, tonic GABAergic background noise was enhanced by GVG. Electron
      micrographs from inhibitory synapses identified by immunogold staining for GABA
      confirmed the enhanced GABA content but revealed no further morphological
      alterations. 4. The suppression of GABA synthesis by MPA had opposite functional
      consequences: mIPSC amplitude and frequency decreased and current noise was
      reduced compared with control. However, we were unable to demonstrate the
      decreased GABA content in biochemical analyses of whole slices or in electron
      micrographs. 5. We conclude that the transmitter content of GABAergic vesicles is
      variable and that postsynaptic receptors are usually not saturated, leaving room
      for up-regulation of inhibitory synaptic strength. Our data reveal a new
      mechanism of plasticity at central inhibitory synapses and provide a rationale
      for the activity-dependent regulation of GABA synthesis in mammals.

PMID- 11533138
TI  - Properties and plasticity of synaptic inputs to rat dorsal column neurones
      recorded in vitro.
AB  - 1. The mechanisms regulating the flow of sensory signals and their modification
      by synaptic interactions in the dorsal column nuclei are incompletely understood.
      Therefore, we examined the interactions between EPSPs evoked by stimulation of
      dorsal column and corticofugal fibres in the dorsal column nuclei cells using an
      in vitro slice technique. 2. Dorsal column EPSPs had briefer durations at
      depolarised membrane potentials than corticofugal EPSPs. Superfusion of the NMDA
      receptor antagonist 2D(-)-2-amino-5-phosphonovaleric acid (AP5) did not modify
      dorsal column EPSPs but reduced corticofugal EPSPs. Application of the
      AMPA/kainate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX)
      abolished both dorsal column and corticofugal EPSPs in cells held at the resting
      potential. Therefore, dorsal column EPSPs were mediated by non-NMDA receptors but
      corticofugal EPSPs revealed both non-NMDA- and NMDA-dependent components. 3.
      Paired-pulse stimulation of dorsal column fibres elicited a depression of the
      second EPSP at pulse intervals of < 50 ms; however, paired-pulse stimulation of
      corticofugal fibres evoked facilitation of the second EPSP at pulse intervals of
      < 30 ms. When stimulation of the corticofugal fibres preceded stimulation of the
      dorsal column fibres, facilitation of the dorsal column EPSP was observed at
      pulse intervals of < 100 ms. This facilitation was blocked at hyperpolarised
      membrane potentials or in the presence of AP5, suggesting activation of NMDA
      receptors. There was a depression of corticofugal EPSPs by previous dorsal column
      stimulation. 4. Dorsal column EPSPs were gradually depressed during stimulation
      with barrages at frequencies of > 10 Hz, while corticofugal EPSPs were
      facilitated and summated at frequencies > 30 Hz. Hyperpolarisation and
      application of AP5 prevented the facilitation of corticofugal EPSPs. High
      frequency stimulation of the corticofugal input elicited a short-lasting AP5
      sensitive facilitation of both corticofugal and dorsal column EPSPs. Depolarising
      current facilitated dorsal column EPSPs but not corticofugal EPSPs. 5. These
      results indicate that synaptic interactions include different forms of activity
      dependent synaptic plasticity, with the participation of NMDA receptors and
      probably Ca(2+) inflow through voltage-gated channels. These complex synaptic
      interactions may represent the cellular substrate of the integrative function of
      the dorsal column nuclei observed in vivo.

PMID- 11533139
TI  - Multiple transport functions of a red blood cell anion exchanger, tAE1: its role
      in cell volume regulation.
AB  - 1. It was previously shown that expressed in Xenopus oocyte the mouse (mAE1) and
      the trout (tAE1) anion exchanger behave differently: both elicit anion exchange
      activity but only tAE1 induces a transport of organic solutes correlated with a
      chloride channel activity. The present data, obtained by measurement of Xenopus
      oocyte membrane permeability and conductance, provide evidence that tAE1 also
      induces a large increase in Na(+) and K(+) permeability inhibited by several AE1
      inhibitors. 2. This inhibition does not result from an effect on the driving
      force for electrodiffusion but represents a direct effect on the cation pathway.
      3. As a control, expression of cystic fibrosis transmembrane conductance
      regulator (CFTR) having, once stimulated by 3-isobutyl-1-methylxanthine (IBMX),
      the same anion conductance magnitude as tAE1 did not induce any cation movement.
      4. Chloride exchange, channel activity and cation transport induced by anion
      exchanger expression are inhibited by free or covalently bound H2DIDS as well.
      This covalent inhibition is reversed by the point mutation of Lys-522, the
      covalent binding site of H2DIDS to the protein. These data reveal that tAE1
      itself acts both as an anion exchanger and as a channel of broad selectivity. 5.
      All results obtained by expression of AE1 isoforms in Xenopus oocytes and those
      obtained in erythrocytes are consistent with the proposal that, in nucleated
      erythrocytes, tAE1 functions as the swelling-activated osmolyte anion channel
      involved in cell volume regulation. In contrast AE1 from mammalian red cells,
      which do not regulate their volume, lacks swelling-activated osmolyte channel
      properties. 6. tAE1 illustrates the ability of a specific transport system to be
      a multifunctional protein exhibiting other transport functions when submitted to
      regulation.

PMID- 11533140
TI  - Nitric oxide-cGMP pathway facilitates acetylcholine release and bradycardia
      during vagal nerve stimulation in the guinea-pig in vitro.
AB  - 1. We tested the hypothesis that nitric oxide (NO) augments vagal
      neurotransmission and bradycardia via phosphorylation of presynaptic calcium
      channels to increase vesicular release of acetylcholine. 2. The effects of enzyme
      inhibitors and calcium channel blockers on the actions of the NO donor sodium
      nitroprusside (SNP) were evaluated in isolated guinea-pig atrial-right vagal
      nerve preparations. 3. SNP (10 microM) augmented the heart rate response to vagal
      nerve stimulation but not to the acetylcholine analogue carbamylcholine (100 nM).
      SNP also increased the release of [3H]acetylcholine in response to field
      stimulation. No effect of SNP was observed on either the release of [3H]
      acetylcholine or the HR response to vagal nerve stimulation in the presence of
      the guanylyl cyclase inhibitor 1H-(1,2,4)-oxadiazolo-(4,3-a)-quinoxalin-1-one
      (ODQ, 10 microM). 4. The phosphodiesterase 3 (PDE 3) inhibitor milrinone (1
      microM) increased the release of [3H] acetylcholine and the vagal bradycardia and
      prevented any further increase by SNP. SNP was still able to augment the vagal
      bradycardia in the presence of the protein kinase G inhibitor KT5823 (1 microM)
      but not after protein kinase A (PKA) inhibition with H-89 (0.5 microM) or KT5720
      (1 microM) had reduced the HR response to vagal nerve stimulation. Neither
      milrinone nor H-89 changed the HR response to carbamylcholine. 5. SNP had no
      effect on the magnitude of the vagal bradycardia after inhibition of N-type
      calcium channels with omega-conotoxin GVIA (100 nM). 6. These results suggests
      that NO acts presynaptically to facilitate vagal neurotransmission via a cGMP-PDE
      3-dependent pathway leading to an increase in cAMP-PKA-dependent phosphorylation
      of presynaptic N-type calcium channels. This pathway may augment the HR response
      to vagal nerve stimulation by increasing presynaptic calcium influx and vesicular
      release of acetylcholine.

PMID- 11533141
TI  - Somatostatin inhibits exocytosis in rat pancreatic alpha-cells by G(i2)-dependent
      activation of calcineurin and depriming of secretory granules.
AB  - 1. Measurements of cell capacitance were used to investigate the molecular
      mechanisms by which somatostatin inhibits Ca(2+)-induced exocytosis in single rat
      glucagon-secreting pancreatic alpha-cells. 2. Somatostatin decreased the
      exocytotic responses elicited by voltage-clamp depolarisations by 80 % in the
      presence of cyclic AMP-elevating agents such as isoprenaline and forskolin.
      Inhibition was time dependent and half-maximal within 22 s. 3. The inhibitory
      action of somatostatin was concentration dependent with an IC(50) of 68 nM and
      prevented by pretreatment of the cells with pertussis toxin. The latter effect
      was mimicked by intracellular dialysis with specific antibodies to G(i1/2) and by
      antisense oligonucleotides against G proteins of the subtype G(i2). 4.
      Somatostatin lacked inhibitory action when applied in the absence of forskolin or
      in the presence of the L-type Ca(2+) channel blocker nifedipine. The size of the
      omega-conotoxin-sensitive and forskolin-independent component of exocytosis was
      limited to 60 fF. By contrast, somatostatin abolished L-type Ca(2+) channel
      dependent exocytosis in alpha-cells exposed to forskolin. The magnitude of the
      latter pool amounted to 230 fF. 5. The inhibitory effect of somatostatin on
      exocytosis was mediated by activation of the serine/threonine protein phosphatase
      calcineurin and was prevented by pretreatment with cyclosporin A and deltamethrin
      or intracellularly applied calcineurin autoinhibitory peptide. Experiments using
      the stable ATP analogue AMP-PCP indicate that somatostatin acts by depriming of
      granules. 6. We propose that somatostatin receptors associate with L-type Ca(2+)
      channels and couple to G(i2) proteins leading to a localised activation of
      calcineurin and depriming of secretory granules situated close to the L-type
      Ca(2+) channels.

PMID- 11533142
TI  - Impact of the renin-angiotensin system on cerebral perfusion following
      subarachnoid haemorrhage in the rat.
AB  - 1. This study investigated the effects of blocking the AT1 angiotensin receptors
      with irbesartan, either peripherally or centrally, on systemic blood pressure,
      intracranial pressure and cerebral perfusion pressure following experimental
      subarachnoid haemorrhage (SAH) in urethane-anaesthetized rats. Sympathetic
      nervous activation was determined by measuring plasma noradrenaline levels. 2. In
      untreated animals, SAH induced a sustained increased in intracranial pressure
      from 2.1 +/- 0.3 to 16 +/- 2 mmHg (3 h, P < 0.001). Cerebral perfusion pressure
      was reduced by 20 % (P < 0.001), this reduction being maintained for 3 h.
      Sympathetic activation was evident in the high level of plasma noradrenaline
      measured 3 h post-SAH (751 +/- 104 vs. 405 +/- 33 pg ml(-1), P < 0.05). 3. Acute
      peripheral pretreatment with irbesartan (3 mg kg(-1), I.V.) prevented the rise in
      plasma noradrenaline and further aggravated the decrease in cerebral perfusion
      pressure by producing transient systemic hypotension (blood pressure was 85 +/- 6
      mmHg at 2 h post-SAH vs. 100 +/- 3 mmHg, P < 0.01). 4. Intracisternal
      pretreatment with irbesartan (0.035 mg) did not prevent the rise in plasma
      noradrenaline post-SAH but enhanced the rise in intracranial pressure by 75 %
      compared with untreated animals. 5. This study demonstrates that peripheral
      endogenous angiotensin II interacts with the sympathetic nervous system in order
      to maintain an adequate cerebral perfusion following SAH. Endogenous angiotensin
      II in the brain seems to exert a protective effect by counteracting the elevation
      in intracranial pressure that occurs following experimental SAH.

PMID- 11533143
TI  - Permeability of human HT-29/B6 colonic epithelium as a function of apoptosis.
AB  - 1. The barrier function of colonic epithelia is challenged by apoptotic loss of
      enterocytes. In monolayers of human colonic HT-29/B6 cells, apoptosis induced by
      camptothecin was assessed by poly-(ADP-ribose)-polymerase (PARP) cleavage,
      histone ELISA and DNA-specific fluorochrome staining (with 4',6'-diamidino-2'
      phenylindoladihydrochloride (DAPI)). Epithelial barrier function was studied in
      Ussing chambers by measuring transepithelial conductivity and unidirectional
      tracer fluxes. The ion permeability associated with single cell apoptoses was
      investigated with the conductance scanning technique. 2. The spontaneous rate of
      apoptotic cells was 3.5 +/- 0.3 % with an overall epithelial conductivity of 3.2
      +/- 0.1 mS cm(-2). Camptothecin induced a time- and dose-dependent increase of
      apoptosis and permeability. With 20 microg ml(-1) of camptothecin for 48 h,
      apoptosis increased 4.1-fold to 14.3 +/- 1.5 % and the conductivity doubled to
      6.4 +/- 1.0 mS cm(-2). 3. While 3H-mannitol flux increased 3.8-fold and 3H
      lactulose flux increased 2.6-fold, the flux of 3H-polyethylene glycol 4000
      remained unchanged. Hence, the higher permeability was limited to molecules <
      4000 Da. 4. The local epithelial conductivity was higher at the sites of
      apoptosis than in non-apoptotic areas. With camptothecin the leaks associated
      with apoptosis became more numerous and more conductive, while in non-apoptotic
      areas the conductivity remained at control level. Hence, the camptothecin-induced
      increase in epithelial conductivity reflected the opening of apoptotic leaks and
      thus the results described, for the first time, epithelial permeability as a
      function of apoptosis only. 5. The conductivity of apoptotic leaks contributed
      5.5 % to the epithelial conductivity of controls and 60 % to the conductivity of
      monolayers treated with 20 microg ml(-1) of camptothecin. Thus apoptosis
      increased the contribution of paracellular pathways to the overall epithelial
      permeability. Under control conditions the paracellular conductivity (G(para))
      was smaller than the transcellular (G(trans)), but with 12 % apoptosis, G(para)
      exceeded G(trans). By definition, the epithelium became 'leaky'.

PMID- 11533144
TI  - Expression of CPI-17 and myosin phosphatase correlates with Ca(2+) sensitivity of
      protein kinase C-induced contraction in rabbit smooth muscle.
AB  - 1. Various smooth muscles have unique contractile characteristics, such as the
      degree of Ca(2+) sensitivity induced by physiological and pharmacological agents.
      Here we evaluated six different rabbit smooth muscle tissues for protein kinase C
      (PKC)-induced Ca(2+) sensitization. We also examined the expression levels of
      myosin light chain phosphatase (MLCP), the MLCP inhibitor phosphoprotein CPI-17,
      and the thin filament regulator h-calponin. 2. Immunohistochemical and Western
      blot analyses indicated that CPI-17 was found primarily in smooth muscle,
      although expression varied among different tissues. Vascular muscles contained
      more CPI-17 than visceral muscles, with further distinction existing between
      tonic and phasic subtypes. For example, the tonic femoral artery possessed
      approximately 8 times the cellular CPI-17 concentration of the phasic vas
      deferens. 3. In contrast to CPI-17 expression patterns, phasic muscles contained
      more MLCP myosin-targeting subunit than tonic tissues. Calponin expression was
      not statistically different. 4. Addition of phorbol ester to alpha-toxin
      permeabilized smooth muscle caused an increase in contraction and phosphorylation
      of both CPI-17 and myosin light chain (MLC) at submaximal [Ca(2+)]i. These
      responses were several-fold greater in femoral artery as compared to vas
      deferens. 5. We conclude that the expression ratio of CPI-17 to MLCP correlates
      with the Ca(2+) sensitivities of contraction induced by a PKC activator. PKC
      stimulation of arterial smooth muscle with a high CPI-17 and low MLCP expression
      generated greater force and MLC phosphorylation than stimulation of visceral
      muscle with a relatively low CPI-17 and high MLCP content. This implicates CPI-17
      inhibition of MLCP as an important component in modulating vascular muscle tone.

PMID- 11533145
TI  - Spatial and temporal coordination of junction potentials in circular muscle of
      guinea-pig distal colon.
AB  - 1. In isolated, stretched, flat-sheet preparations of guinea-pig distal colon,
      simultaneous intracellular recordings were made from pairs of circular muscle
      (CM) cells to map the region of smooth muscle at which spontaneous junction
      potentials (sJPs) were coordinated in both space and time. 2. Spontaneous
      inhibitory junction potentials (sIJPs) and excitatory junction potentials (sEJPs)
      were recorded from all animals with varying frequencies and amplitudes (up to 25
      mV). 3. Large amplitude (> or = 9 mV) sIJPs or sEJPs with near-identical
      amplitudes and time courses were recorded synchronously from two CM cells, even
      when the two electrodes were separated by up to 11 mm in the circumferential axis
      and < or = 4 mm in the longitudinal axis. However, smaller (< 9 mV) sIJPs or
      sEJPs were less coordinated and exhibited greater variability in their times to
      peak. 4. The standard deviation (S.D.) for the time difference between the peaks
      of sJPs was related to the amplitude of the events and the distance between the
      electrodes. The S.D. for large amplitude JPs (approximately 30 ms), which was
      less than that for small JPs (approximately 150 ms), remained constant across the
      circumferential axis (at least up to 6 mm), but declined rapidly for distances >
      or = 2 mm in the longitudinal axis. 5. Current injection (up to 8 nA) into a
      single CM cell elicited electrotonic potentials in neighbouring CM cells, only
      when the two electrodes were separated by less than 100 microm circumferentially.
      Beyond 50 microm electronic potentials were rarely detected. 6. Tetrodotoxin
      (TTX; 1 microM) abolished all sJPs, whereas hexamethonium (300 microM) either
      abolished, or substantially reduced all sJPs. 7. Nitro-L-arginine (L-NA; 100
      microM) abolished the slow repolarisation phase of sIJPs without any apparent
      effect on the amplitude of sIJPs. Apamin abolished the fast, initial component of
      sIJPs, suggesting synchronous release of two inhibitory neurotransmitters during
      the sIJP. Atropine (1 microM) abolished sEJPs. 8. No sJPs were recorded from the
      CM layer when it was separated from the myenteric plexus. 9. In conclusion, sIJPs
      and sEJPs in colonic CM occur synchronously over large regions of the smooth
      muscle syncitium. The results are discussed in relation to the idea that
      spontaneous junction potentials in colonic CM are not monoquantal events, but are
      generated by the simultaneous release of transmitter from many release sites, due
      to the synchronous activation of many enteric motor neurons.

PMID- 11533146
TI  - Normal conduction of surface action potentials in detubulated amphibian skeletal
      muscle fibres.
AB  - 1. The influence of the transverse (T) tubules on surface action potential
      conduction was investigated by comparing electrophysiological and confocal
      microscopic assessments of tubular changes in osmotically shocked and control
      fibres from frog sartorius muscle. 2. The membrane-impermeant fluorescent dye, di
      8-ANEPPs spread readily from the bathing extracellular solution into the tubular
      membranes in control, intact fibres. Prior exposure of muscles to a hypertonic
      glycerol-Ringer solution, its replacement by an isotonic Ca(2+)-Mg(2+) Ringer
      solution and cooling sharply reduced such access. In contrast, dye application in
      the course of this osmotic shock procedure stained the large tubular vacuoles
      hitherto associated with successful muscle detubulation. 3. Conduction velocities
      in intact, control fibres (1.91 +/- 0.048 m s(-1), mean +/- S.E.M., n = 32
      fibres) agreed with earlier values reported at room temperature (18-21 degrees C)
      and were unaffected by prior episodes of steady cooling to 8-10 degrees C (1.91
      +/- 0.043 m s(-1), n = 30). 4. Cooling to 11.5 degrees C reduced these velocities
      (1.47 +/- 0.081 m s(-1), n = 25) but action potential waveforms still included
      early overshoots and the delayed after-depolarizations associated with tubular
      electrical activity. 5. In contrast, action potentials from cooled, superficial
      fibres in osmotically shocked muscles lacked after-depolarization phases implying
      tubular detachment. Their mean conduction velocities (1.62 +/- 0.169 m s(-1), n =
      25) were not significantly altered from values obtained in untreated controls or
      in intact fibres in muscle similarly treated with glycerol, in direct contrast to
      earlier results. 6. Cooling produced similar reductions in maximum rates of
      voltage change dV/dt in action potentials from all fibre groups with lower rates
      of change shown by detubulated fibres. 7. Use of an antibody to a conserved
      epitope of the alpha-subunit of voltage-gated sodium channels suggested a
      concentration of sodium channels close to the mouths of the T tubules. 8. These
      electrophysiological and anatomical findings are consistent with a partial
      independence of electrical events in the transverse tubules from those
      responsible for the rapid conduction of surface regenerative activity. 9. The
      findings are discussed in terms of a partial separation of the electrical
      activity propagated over the surface membrane, from the initiation of propagated
      activity within the T tubules, by the triggering of the sodium channels clustered
      selectively around the mouths of the T tubules.

PMID- 11533147
TI  - Force and power output of fast and slow skeletal muscles from mdx mice 6-28
      months old.
AB  - 1. Differences in the effect of age on structure-function relationships of limb
      muscles of mdx (dystrophin null) and control mice have not been resolved. We
      tested the hypotheses that, compared with limb muscles from age-matched control
      mice, limb muscles of 6- to 17-month-old mdx mice are larger but weaker, with
      lower normalised force and power, whereas those from 24- to 28-month-old mdx mice
      are smaller and weaker. 2. The maximum isometric tetanic force (P(o)) and power
      output of limb muscles from 6-, 17-, 24- and 28-month-old mdx and control mice
      were measured in vitro at 25 degrees C and normalised with respect to cross
      sectional area and muscle mass, respectively. 3. Body mass at 6 and 28 months was
      not significantly different in mdx and control mice, but that of control mice
      increased 16 % by 17 months and then declined 32 % by 28 months. The body masses
      of mdx mice declined linearly with age with a decrease of 25 % by 28 months. From
      6 to 28 months of age, the range in the decline in the masses of EDL and soleus
      muscles of mdx and control mice was from 16 to 28 %. The muscle masses of mdx
      mice ranged from 9 % to 42 % greater than those of control mice at each of the
      four ages and, even at 28 months, the masses of EDL and soleus muscles of mdx
      mice were 17 % and 22 % greater than control values. 4. For mdx mice of all ages,
      muscle hypertrophy was highly effective in the maintenance of control values for
      absolute force for both EDL and soleus muscles and for absolute power of soleus
      muscles. Throughout their lifespan, muscles of mdx mice displayed significant
      weakness with values for specific P(o) and normalised power approximately 20 %
      lower than values for control mice at each age. For muscles of both strains,
      normalised force and power decreased approximately 28 % with age, and
      consequently weakness was more severe in muscles of old mdx than in those of old
      control mice.

PMID- 11533148
TI  - Thermogenesis induced by intravenous infusion of hypertonic solutions in the rat.
AB  - 1. Intravenous administration of 20-60 % glucose, 3.2-9.7 % NaCl or 20 % mannitol
      solutions (1.66 ml kg(-1)) for 5 min increased oxygen consumption in urethane
      anaesthetized rats, whereas administration of physiological saline had no effect.
      Administration of 7.7-18.3 % urea slightly increased the oxygen consumption, but
      the increase was significantly smaller than that measured after the
      administration of other hypertonic solutions. The magnitude of the thermogenic
      effect correlated with the osmolality of the applied solutions. These results
      suggest that the thermogenesis was caused mainly by changes in osmolality rather
      than by a specific action of the different solute molecules. 2. Neither
      pretreatment with the ganglion blocker hexamethonium (20 mg kg(-1), I.P.) or the
      beta-adrenergic antagonist propranolol (10 mg kg(-1), I.P.), nor bilateral
      cervical vagotomy or bilateral adrenalectomy had any effect on the osmotically
      induced thermogenesis. Therefore, the autonomic nervous system and the adrenal
      gland were not involved in this metabolic response. 3. In response to osmotic
      stimulation, the temperature of the skeletal muscle increased significantly,
      whereas that of brown adipose tissue did not change and that of the colon and
      liver decreased. Accordingly, the site of osmotic thermogenesis is probably in
      the skeletal muscle, although osmotic stimulation was not accompanied by
      electromyographic activity and was not blocked by pretreatment with muscle
      relaxants such as dantrolene sodium or pancuronium bromide, or with the Na(+)-Cl(
      ) co-transport inhibitor bumetanide. 4. The increases in plasma osmolality
      observed after the administration of 20 % (1.3 osmol kg(-1)) glucose and 4.1 %
      (1.3 osmol kg(-1)) NaCl were 4.50 +/- 0.88 and 5.57 +/- 0.71 mosmol kg(-1),
      respectively. Since the slight increase in osmolality is well within the
      physiological range of changes that occur after food ingestion, diet-induced
      thermogenesis may have a component that is mediated by an increase in plasma
      osmolality, which results from the prandial increase in circulating nutrients.

PMID- 11533149
TI  - Cardiac performance in inbred rat genetic models of low and high running
      capacity.
AB  - 1. Previous work demonstrating that DA inbred rats are superior to COP inbred
      rats in aerobic treadmill running capacity has indicated their utility as genetic
      models to explore this trait. We tested the general hypothesis that intermediate
      phenotypes of cardiac function and calcium metabolism are responsible for the
      difference in capacity between these strains. 2. Logical cardiac trait
      differences were estimated at a tissue (isolated papillary muscle), cellular
      (isolated left ventricular cells), and biochemical level of organization. 3. DA
      hearts were found to give significantly higher values than COP hearts for: (1)
      maximal developed tension (38.3 % greater), and rates of tension change in
      contraction (61 %) or relaxation (59 %) of isolated papillary muscle, (2)
      fractional shortening (50 %), amplitude of the Ca(2+) transient (78.6 %), and
      caffeine-induced release of Ca(2+) from the sarcoplasmic reticulum (SR; 260 %) in
      isolated ventricular myocytes, and (3) Na(+),K(+)-ATPase activity of isolated
      myocytes (17.3 %). 4. Our results suggest that these trait differences may prove
      useful for further studies into the genes responsible for natural variations in
      both ventricular function and aerobic endurance capacity. Understanding the
      genetic basis of aerobic capacity will help define the continuum between health
      and disease.

PMID- 11533150
TI  - Motion sickness potentiates core cooling during immersion in humans.
AB  - 1. The present study tested the hypothesis that motion sickness affects
      thermoregulatory responses to cooling in humans. 2. Ten healthy male volunteers
      underwent three separate head-out immersions in 28 degrees C water after
      different preparatory procedures. In the 'control' procedure immersion was
      preceded by a rest period. In the 'motion sickness' procedure immersion was
      preceded by provocation of motion sickness in a human centrifuge. This comprised
      rapid and repeated alterations of the gravitational (G-) stress in the head-to
      foot direction, plus a standardized regimen of head movements at increased G
      stress. In the 'G-control' procedure, the subjects were exposed to similar G
      stress, but without the motion sickness provocation. 3. During immersion mean
      skin temperature, rectal temperature, the difference in temperature between the
      forearm and 3rd digit of the right hand (DeltaT(forearm-fingertip)), oxygen
      uptake and heart rate were recorded. Subjects provided ratings of temperature
      perception, thermal comfort and level of motion sickness discomfort at regular
      intervals. 4. No differences were observed in any of the variables between
      control and G-control procedures. In the motion sickness procedure, the
      DeltaT(forearm-fingertip) response was significantly attenuated, indicating a
      blunted vasoconstrictor response, and rectal temperature decreased at a faster
      rate. No other differences were observed. 5. Motion sickness attenuates the
      vasoconstrictor response to skin and core cooling, thereby enhancing heat loss
      and the magnitude of the fall in deep body temperature. Motion sickness may
      predispose individuals to hypothermia, and have significant implications for
      survival time in maritime accidents.

PMID- 11533151
TI  - Inhibition of TRAIL-induced apoptosis and forced internalization of TRAIL
      receptor 1 by adenovirus proteins.
AB  - Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) induces
      apoptosis through two receptors, TRAIL-R1 (also known as death receptor 4) and
      TRAIL-R2 (also known as death receptor 5), that are members of the TNF receptor
      superfamily of death domain-containing receptors. We show that human adenovirus
      type 5 encodes three proteins, named RID (previously named E3-10.4K/14.5K), E3
      14.7K, and E1B-19K, that independently inhibit TRAIL-induced apoptosis of
      infected human cells. This conclusion was derived from studies using wild-type
      adenovirus, adenovirus replication-competent mutants that lack one or more of the
      RID, E3-14.7K, and E1B-19K genes, and adenovirus E1-minus replication-defective
      vectors that express all E3 genes, RID plus E3-14.7K only, RID only, or E3-14.7K
      only. RID inhibits TRAIL-induced apoptosis when cells are sensitized to TRAIL
      either by adenovirus infection or treatment with cycloheximide. RID induces the
      internalization of TRAIL-R1 from the cell surface, as shown by flow cytometry and
      indirect immunofluorescence for TRAIL-R1. TRAIL-R1 was internalized in distinct
      vesicles which are very likely to be endosomes and lysosomes. TRAIL-R1 is
      degraded, as indicated by the disappearance of the TRAIL-R1 immunofluorescence
      signal. Degradation was inhibited by bafilomycin A1, a drug that prevents
      acidification of vesicles and the sorting of receptors from late endosomes to
      lysosomes, implying that degradation occurs in lysosomes. RID was also shown
      previously to internalize and degrade another death domain receptor, Fas, and to
      prevent apoptosis through Fas and the TNF receptor. RID was shown previously to
      force the internalization and degradation of the epidermal growth factor
      receptor. E1B-19K was shown previously to block apoptosis through Fas, and both
      E1B-19K and E3-14.7K were found to prevent apoptosis through the TNF receptor.
      These findings suggest that the receptors for TRAIL, Fas ligand, and TNF play a
      role in limiting virus infections. The ability of adenovirus to inhibit killing
      through these receptors may prolong acute and persistent infections.

PMID- 11533152
TI  - Specificity in receptor usage by T-cell-tropic feline leukemia viruses:
      implications for the in vivo tropism of immunodeficiency-inducing variants.
AB  - Cytopathic, T-cell-tropic feline leukemia viruses (FeLV-T) evolve from FeLV-A in
      infected animals and demonstrate host cell specificities that are distinct from
      those of their parent viruses. We recently identified two cellular proteins,
      FeLIX and Pit1, required for productive infection by these immunodeficiency
      inducing FeLV-T variants (M. M. Anderson, A. S. Lauring, C. C. Burns, and J.
      Overbaugh, Science 287:1828-1830, 2000). FeLV-T is the first example of a
      naturally occurring type C retrovirus that requires two proteins to gain entry
      into target cells. FeLIX is an endogenous protein that is highly related to the N
      terminal portion of the FeLV envelope protein, which includes the receptor
      binding domain. Pit1 is a multiple-transmembrane phosphate transport protein that
      also functions as a receptor for FeLV-B. The FeLV-B envelope gene is derived by
      recombination with endogenous FeLV-like sequences, and its product can
      functionally substitute for FeLIX in facilitating entry through the Pit1
      receptor. In the present study, we tested other retrovirus envelope surface units
      (SUs) with their cognate receptors to determine whether they also could mediate
      infection by FeLV-T. Cells were engineered to coexpress the transmembrane form of
      the envelope proteins and their cognate receptors, or SU protein was added as a
      soluble protein to cells expressing the receptor. Of the FeLV, murine leukemia
      virus, and gibbon ape leukemia virus envelopes tested, we found that only those
      with receptor-binding domains derived from endogenous FeLV could render cells
      permissive for FeLV-T. We also found that there is a strong preference for Pit1
      as the transmembrane receptor. Specifically, FeLV-B SUs could efficiently mediate
      infection of cells expressing the Pit1 receptor but could only inefficiently
      mediate infection of cells expressing the Pit2 receptor, even though these SUs
      are able to bind to Pit2. Expression analysis of feline Pit1 and FeLIX suggests
      that FeLIX is likely the primary determinant of FeLV-T tropism. These results are
      discussed in terms of current models for retrovirus entry and the
      interrelationship among FeLV variants that evolve in vivo.

PMID- 11533153
TI  - Hyperattenuated recombinant influenza A virus nonstructural-protein-encoding
      vectors induce human immunodeficiency virus type 1 Nef-specific systemic and
      mucosal immune responses in mice.
AB  - We have generated recombinant influenza A viruses belonging to the H1N1 and H3N2
      virus subtypes containing an insertion of the 137 C-terminal amino acid residues
      of the human immunodeficiency virus type 1 (HIV-1) Nef protein into the influenza
      A virus nonstructural-protein (NS1) reading frame. These viral vectors were found
      to be genetically stable and capable of growing efficiently in embryonated
      chicken eggs and tissue culture cells but did not replicate in the murine
      respiratory tract. Despite the hyperattenuated phenotype of influenza/NS-Nef
      viruses, a Nef and influenza virus (nucleoprotein)-specific CD8(+)-T-cell
      response was detected in spleens and the lymph nodes draining the respiratory
      tract after a single intranasal immunization of mice. Compared to the primary
      response, a marked enhancement of the CD8(+)-T-cell response was detected in the
      systemic and mucosal compartments, including mouse urogenital tracts, if mice
      were primed with the H1N1 subtype vector and subsequently boosted with the H3N2
      subtype vector. In addition, Nef-specific serum IgG was detected in mice which
      were immunized twice with the recombinant H1N1 and then boosted with the
      recombinant H3N2 subtype virus. These findings may contribute to the development
      of alternative immunization strategies utilizing hyperattenuated live recombinant
      influenza virus vectors to prevent or control infectious diseases, e.g., HIV-1
      infection.

PMID- 11533154
TI  - Activation of interferon response factor-3 in human cells infected with herpes
      simplex virus type 1 or human cytomegalovirus.
AB  - Activation of cellular interferon-stimulated genes (ISGs) after infection with
      herpes simplex virus type 1 (HSV-1) or human cytomegalovirus (HCMV) was
      investigated. The level of ISG54-specific RNA in human fetal lung (HFL) or human
      foreskin (BJ) fibroblasts increased substantially after infection with either
      virus in the presence of cycloheximide. HSV-1 particles lacking glycoprotein D or
      glycoprotein H failed to induce ISG54-specific RNA synthesis, demonstrating that
      entry of virus particles rather than binding of virions to the cell surface was
      required for the effect. A DNA-binding complex that recognized an interferon
      responsive sequence motif was induced upon infection with HSV-1 or HCMV in the
      presence of cycloheximide, and the complex was shown to contain the cell proteins
      interferon response factor 3 (IRF-3) and CREB-binding protein. IRF-3 was modified
      after infection with HSV-1 or HCMV to a form of lower electrophoretic mobility,
      consistent with phosphorylation. De novo transcription of viral or cellular genes
      was not required for the activation of IRF-3, since the effect was not sensitive
      to inhibition by actinomycin D. Infection of HFL fibroblasts with HSV-1 under
      conditions in which viral replication proceeded normally resulted in severely
      reduced levels of the IRF-3-containing complex, defining the activation of IRF-3
      as a target for viral interference with ISG induction. In BJ fibroblasts,
      however, significant activation of IRF-3 was detected even when the viral gene
      expression program progressed to later stages, demonstrating that the degree of
      inhibition of the response was dependent on host cell type. As a consequence of
      IRF-3 activation, endogenous interferon was released from BJ cells and was
      capable of triggering the appropriate signal transduction pathway in both
      infected and uninfected cells. Activation of ISG54-specific RNA synthesis was not
      detected after infection of human U-373MG glioblastoma cells, showing that the
      induction of the response by infection is cell type dependent.

PMID- 11533155
TI  - HERV-K(OLD): ancestor sequences of the human endogenous retrovirus family HERV
      K(HML-2).
AB  - Sequences homologous to the human endogenous retrovirus (HERV) family HERV-K(HML
      2) are present in all Old World primate species. A previous study showed that a
      central region of the HERV-K(HML-2) gag genes in Hominoidea species displays a 96
      bp deletion compared to the gag genes in lower Old World primates. The more
      ancient HERV-K(HML-2) sequences present in lower Old World primates were
      apparently not conserved during hominoid evolution, as opposed to the deletion
      variants. To further clarify the evolutionary origin of the HERV-K(HML-2) family,
      we screened GenBank with the 96-bp gag-sequence characteristic of lower Old World
      primates and identified, to date, 10 human sequence entries harboring either full
      length or partially deleted proviral structures, probably representing remnants
      of a more ancient HERV-K(HML-2) variant. The high degree of mutations
      demonstrates the long-time presence of these HERV-K(OLD) proviruses in the
      genome. Nevertheless, they still belong to the HML-2 family as deduced from dot
      matrix and phylogenetic analyses. We estimate, based on the family ages of
      integrated Alu elements and on long terminal repeat (LTR) divergence data, that
      the average age of HERV-K(OLD) proviruses is ca. 28 million years, supporting an
      integration time before the evolutionary split of Hominoidea from lower Old World
      primates. Analysis of HERV-K(OLD) LTR sequences led to the distinction of two
      subgroups, both of which cluster with LTRs belonging to an evolutionarily older
      cluster. Taken together, our data give further insight into the evolutionary
      history of the HERV-K(HML-2) family during primate evolution.

PMID- 11533156
TI  - Pseudorabies virus UL37 gene product is involved in secondary envelopment.
AB  - Herpesvirus envelopment is a two-step process which includes acquisition of a
      primary envelope resulting from budding of intranuclear capsids through the inner
      nuclear membrane. Fusion with the outer leaflet of the nuclear membrane releases
      nucleocapsids into the cytoplasm, which then gain their final envelope by budding
      into trans-Golgi vesicles. It has been shown that the UL34 gene product is
      required for primary envelopment of the alphaherpesvirus pseudorabies virus (PrV)
      (B. G. Klupp, H. Granzow, and T. C. Mettenleiter, J. Virol. 74:10063-10073,
      2000). For secondary envelopment, several virus-encoded PrV proteins are
      necessary, including glycoproteins E, I, and M (A. R. Brack, J. M. Dijkstra, H.
      Granzow, B. G. Klupp, and T. C. Mettenleiter, J. Virol. 73:5364-5372, 1999). We
      show here that the product of the UL37 gene of PrV, which is a constituent of
      mature virions, is involved in secondary envelopment. Replication of a UL37
      deletion mutant, PrV-DeltaUL37, was impaired in normal cells; this defect could
      be complemented on cells stably expressing UL37. Ultrastructural analysis
      demonstrated that intranuclear capsid maturation and budding of capsids into and
      release from the perinuclear space were unimpaired. However, secondary
      envelopment was drastically reduced. Instead, apparently DNA-filled capsids
      accumulated in the cytoplasm in large aggregates similar to those observed in the
      absence of glycoproteins E/I and M but lacking the surrounding electron-dense
      tegument material. Although displaying an ordered structure, capsids did not
      contact each other directly. We postulate that the UL37 protein is necessary for
      correct addition of other tegument proteins, which are required for secondary
      envelopment. In the absence of the UL37 protein, capsids interact with each other
      through unknown components but do not acquire the electron-dense tegument which
      is normally found around wild-type capsids during and after secondary
      envelopment. Thus, apposition of the UL37 protein to cytoplasmic capsids may be
      crucial for the addition of other tegument proteins, which in turn are able to
      interact with viral glycoproteins to mediate secondary envelopment.

PMID- 11533157
TI  - Replication of the wild type and a natural hepatitis B virus nucleocapsid
      promoter variant is differentially regulated by nuclear hormone receptors in cell
      culture.
AB  - A natural hepatitis B virus (HBV) variant associated with seroconversion from
      HBeAg to anti-HBe antibody contains two nucleotide substitutions (A1764T and
      G1766A) in the proximal nuclear hormone receptor binding site in the nucleocapsid
      promoter. These nucleotide substitutions prevent the binding of the retinoid X
      receptor alpha (RXR alpha)-peroxisome proliferator-activated receptor alpha (PPAR
      alpha) heterodimer without greatly altering the efficiency of binding of
      hepatocyte nuclear factor 4 (HNF4) to this recognition sequence. In addition,
      these nucleotide substitutions create a new binding site for HNF1. Analysis of
      HBV transcription and replication in nonhepatoma cells indicates that RXR alpha
      PPAR alpha heterodimers support higher levels of pregenomic RNA transcription
      from the wild-type than from the variant nucleocapsid promoter, producing higher
      levels of wild-type than of variant replication intermediates. In contrast, HNF4
      supports higher levels of pregenomic RNA transcription from the variant than from
      the wild-type nucleocapsid promoter, producing higher levels of variant than of
      wild-type replication intermediates. HNF1 can support variant virus replication
      at a low level but is unable to support replication of the wild-type HBV genome.
      These observations indicate that the replication of wild-type and variant viruses
      can be differentially regulated by the liver-specific transcription factors that
      bind to the proximal nuclear hormone receptor binding site of the nucleocapsid
      promoter. Differential regulation of viral replication may be important in the
      selection of specific viral variants as a result of an antiviral immune response.

PMID- 11533158
TI  - In vitro human immunodeficiency virus eradication by autologous CD8(+) T cells
      expanded with inactivated-virus-pulsed dendritic cells.
AB  - Despite significant immune recovery with potent highly active antiretroviral
      therapy (HAART), eradication of human immunodeficiency virus (HIV) from the
      bodies of infected individuals represents a challenge. We hypothesized that an
      inadequate or inappropriate signal in virus-specific antigen presentation might
      contribute to the persistent failure to mount efficient anti-HIV immunity in most
      HIV-infected individuals. Here, we conducted an in vitro study with untreated (n
      = 10) and HAART-treated (n = 20) HIV type 1 (HIV-1) patients which showed that
      pulsing of monocyte-derived dendritic cells (DC) with aldrithiol-2-inactivated
      autologous virus resulted in the expansion of virus-specific CD8(+) T cells which
      were capable of killing HIV-1-infected cells and eradicating the virus from
      cultured patient peripheral blood mononuclear cells independently of the disease
      stages and HAART response statuses of the patients. This in vitro anti-HIV effect
      was further enhanced by the HIV protease inhibitor indinavir (at a nonantiviral
      concentration), which has been shown previously to be able to up-regulate
      directly patient T-cell proliferation following immune stimulation. However,
      following a 2-day treatment with culture supernatant derived from immune
      activated T cells (which mimics an in vivo environment of HIV-disseminated and
      immune-activated lymphoid tissues), DC lost their capacity to present de novo
      inactivated-virus-derived antigens. These findings provide important information
      for understanding the establishment of chronic HIV infection and indicate a
      perspective for clinical use of DC-based therapeutic vaccines against HIV.

PMID- 11533160
TI  - Adeno-associated virus type 2-mediated gene transfer: role of cellular FKBP52
      protein in transgene expression.
AB  - Although adeno-associated virus type 2 (AAV) has gained attention as a
      potentially useful vector for human gene therapy, the transduction efficiencies
      of AAV vectors vary greatly in different cells and tissues in vitro and in vivo.
      We have documented that a cellular tyrosine phosphoprotein, designated the single
      stranded D-sequence-binding protein (ssD-BP), plays a crucial role in AAV
      mediated transgene expression (K. Y. Qing, X.-S. Wang, D. M. Kube, S.
      Ponnazhagan, A. Bajpai, and A. Srivastava, Proc. Natl. Acad. Sci. USA 94:10879
      10884, 1997). We have documented a strong correlation between the phosphorylation
      state of ssD-BP and AAV transduction efficiency in vitro as well as in vivo (K.
      Y. Qing, B. Khuntrirat, C. Mah, D. M. Kube, X.-S. Wang, S. Ponnazhagan, S. Z.
      Zhou, V. J. Dwarki, M. C. Yoder, and A. Srivastava, J. Virol. 72:1593-1599,
      1998). We have also established that the ssD-BP is phosphorylated by epidermal
      growth factor receptor protein tyrosine kinase and that the tyrosine
      phosphorylated form, but not the dephosphorylated form, of ssD-BP prevents AAV
      second-strand DNA synthesis and, consequently, results in a significant
      inhibition of AAV-mediated transgene expression (C. Mah, K. Y. Qing, B.
      Khuntrirat, S. Ponnazhagan, X.-S. Wang, D. M. Kube, M. C. Yoder, and A.
      Srivastava, J. Virol. 72:9835-9841, 1998). Here, we report that a partial amino
      acid sequence of ssD-BP purified from HeLa cells is identical to a portion of a
      cellular protein that binds the immunosuppressant drug FK506, termed the FK506
      binding protein 52 (FKBP52). FKBP52 was purified by using a prokaryotic
      expression plasmid containing the human cDNA. The purified protein could be
      phosphorylated at both tyrosine and serine or threonine residues, and only the
      phosphorylated forms of FKBP52 were shown to interact with the AAV single
      stranded D-sequence probe. Furthermore, in in vitro DNA replication assays,
      tyrosine-phosphorylated FKBP52 inhibited AAV second-strand DNA synthesis by
      greater than 90%. Serine- or threonine-phosphorylated FKBP52 caused approximately
      40% inhibition, whereas dephosphorylated FKBP52 had no effect on AAV second
      strand DNA synthesis. Deliberate overexpression of FKBP52 effectively reduced the
      extent of tyrosine phosphorylation of the protein, resulting in a significant
      increase in AAV-mediated transgene expression in human and murine cell lines.
      These studies corroborate the idea that the phosphorylation status of the
      cellular FKBP52 protein correlates strongly with AAV transduction efficiency,
      which may have important implications for the optimal use of AAV vectors in human
      gene therapy.

PMID- 11533159
TI  - Antigenically distinct conformations of CXCR4.
AB  - The major human immunodeficiency virus type 1 (HIV-1) coreceptors are the
      chemokine receptors CCR5 and CXCR4. The patterns of expression of the major
      coreceptors and their use by HIV-1 strains largely explain viral tropism at the
      level of entry. However, while virus infection is dependent upon the presence of
      CD4 and an appropriate coreceptor, it can be influenced by a number of factors,
      including receptor concentration, affinity between envelope gp120 and receptors,
      and potentially receptor conformation. Indeed, seven-transmembrane domain
      receptors, such as CCR5, can exhibit conformational heterogeneity, although the
      significance for virus infection is uncertain. Using a panel of monoclonal
      antibodies (MAbs) to CXCR4, we found that CXCR4 on both primary and transformed T
      cells as well as on primary B cells exhibited considerable conformational
      heterogeneity. The conformational heterogeneity of CXCR4 explains the cell-type
      dependent ability of CXCR4 antibodies to block chemotaxis to stromal cell-derived
      factor 1 alpha and to inhibit HIV-1 infection. In addition, the MAb most commonly
      used to study CXCR4 expression, 12G5, recognizes only a subpopulation of CXCR4
      molecules on all primary cell types analyzed. As a result, CXCR4 concentrations
      on these important cell types have been underestimated to date. Finally, while
      the factors responsible for altering CXCR4 conformation are not known, we found
      that they do not involve CXCR4 glycosylation, sulfation of the N-terminal domain
      of CXCR4, or pertussis toxin-sensitive G-protein coupling. The fact that this
      important HIV-1 coreceptor exists in multiple conformations could have
      implications for viral entry and for the development of receptor antagonists.

PMID- 11533161
TI  - Effects of mutations within the herpes simplex virus type 1 DNA encapsidation
      signal on packaging efficiency.
AB  - The cis-acting signals required for cleavage and encapsidation of the herpes
      simplex virus type 1 genome lie within the terminally redundant region or a
      sequence. The a sequence is flanked by short direct repeats (DR1) containing the
      site of cleavage, and quasi-unique regions, Uc and Ub, occupy positions adjacent
      to the genomic L and S termini, respectively, such that a novel fragment, Uc-DR1
      Ub, is generated upon ligation of the genomic ends. The Uc-DR1-Ub fragment can
      function as a minimal packaging signal, and motifs have been identified within Uc
      and Ub that are conserved near the ends of other herpesvirus genomes (pac2 and
      pac1, respectively). We have introduced deletion and substitution mutations
      within the pac regions of the Uc-DR1-Ub fragment and assessed their effects on
      DNA packaging in an amplicon-based transient transfection assay. Within pac2,
      mutations affecting the T tract had the greatest inhibitory effect, but deletion
      of sequences on either side of this element also reduced packaging, suggesting
      that its position relative to other sequences within the Uc-DR1-Ub fragment is
      likely to be important. No single region essential for DNA packaging was detected
      within pac1. However, mutants lacking the G tracts on either side of the pac1 T
      rich motif exhibited a reduced efficiency of serial propagation, and alteration
      of the sequences between DR1 and the pac1 T element also resulted in defective
      generation of Ub-containing terminal fragments. The data are consistent with a
      model in which initiation and termination of packaging are specified by sequences
      within Uc and Ub, respectively.

PMID- 11533162
TI  - Study of the mechanism of antiviral action of iminosugar derivatives against
      bovine viral diarrhea virus.
AB  - The glucose-derived iminosugar derivatives N-butyl- and N-nonyl-deoxynojirimycin
      (DNJ) have an antiviral effect against a broad spectrum of viruses including
      Bovine viral diarrhea virus (BVDV). For BVDV, this effect has been attributed to
      the reduction of viral secretion due to an impairment of viral morphogenesis
      caused by the ability of DNJ-based iminosugar derivatives to inhibit ER alpha
      glucosidases (N. Zitzmann, A. S. Mehta, S. Carrouee, T. D. Butters, F. M. Platt,
      J. McCauley, B. S. Blumberg, R. A. Dwek, and T. M. Block, Proc. Natl. Acad. Sci.
      USA 96:11878-11882, 1999). Here we present the antiviral features of newly
      designed DNJ derivatives and report for the first time the antiviral activity of
      long-alkyl-chain derivatives of deoxygalactonojirimycin (DGJ), a class of
      iminosugars derived from galactose which does not inhibit endoplasmic reticulum
      (ER) alpha-glucosidases. We demonstrate the lack of correlation between the
      ability of long-alkyl-chain DNJ derivatives to inhibit ER alpha-glucosidases and
      their antiviral effect, ruling out ER alpha-glucosidase inhibition as the sole
      mechanism responsible. Using short- and long-alkyl-chain DNJ and DGJ derivatives,
      we investigated the mechanisms of action of these drugs. First, we excluded their
      potential action at the level of the replication, protein synthesis, and protein
      processing. Second, we demonstrated that DNJ derivatives cause both a reduction
      in viral secretion and a reduction in the infectivity of newly released viral
      particles. Long-alkyl-chain DGJ derivatives exert their antiviral effect solely
      via the production of viral particles with reduced infectivity. We demonstrate
      that long-alkyl-chain DNJ and DGJ derivatives induce an increase in the quantity
      of E2-E2 dimers accumulated within the ER. The subsequent enrichment of these
      homodimers in secreted virus particles correlates with their reduced infectivity.

PMID- 11533163
TI  - Hemagglutinin-neuraminidase-independent fusion activity of simian virus 5 fusion
      (F) protein: difference in conformation between fusogenic and nonfusogenic F
      proteins on the cell surface.
AB  - The fusion (F) protein of simian virus 5 (SV5) strain W3A is known to induce cell
      fusion in the absence of hemagglutinin-neuraminidase (HN) protein. In contrast,
      the F protein of SV5 strain WR induces cell fusion only when coexpressed with the
      HN protein, the same as do other paramyxovirus F proteins. When Leu-22 in the
      subunit F2 of the WR F protein is replaced with the counterpart (Pro) in the W3A
      F protein, the resulting mutant L22P induces extensive cell fusion by itself. In
      the present study, we obtained anti-L22P monoclonal antibodies (MAbs) 21-1 and 6
      7, whose epitopes were located in the middle (amino acids [aa] 227 to 320) of
      subunit F1. The amino-terminal region (aa 20 to 47) of subunit F2 was also
      involved in the formation of MAb 21-1 epitope. Flow cytometric analysis revealed
      that both the MAbs reacted very faintly with native WR F protein that was
      expressed on the cell surface whereas they reacted efficiently with native L22P
      irrespective of whether it is cleaved into F1 and F2. However, by heating the
      cells at 47 degrees C after mild formaldehyde fixation, the epitopes for MAb 6-7
      and mAb 21-1 in the WR F protein were exposed and the reactivity of the MAbs with
      the WR F protein became comparable to their reactivity with L22P. Thus, the two
      MAbs seem to distinguish the difference in native conformation between fusogenic
      mutant L22P and its parental nonfusogenic WR F protein. The native conformation
      of L22P may represent an intermediate between native and postfusion conformations
      of a typical paramyxovirus F protein.

PMID- 11533164
TI  - Tyrosine phosphorylation of bovine herpesvirus 1 tegument protein VP22 correlates
      with the incorporation of VP22 into virions.
AB  - Tyrosine phosphorylation has been shown to play a role in the replication of
      several herpesviruses. In this report, we demonstrate that bovine herpesvirus 1
      infection triggered tyrosine phosphorylation of proteins with molecular masses
      similar to those of phosphorylated viral structural proteins. One of the tyrosine
      phosphorylated viral structural proteins was the tegument protein VP22. A
      tyrosine 38-to-phenylalanine mutation totally abolished the phosphorylation of
      VP22 in transfected cells. However, construction of a VP22 tyrosine 38-to
      phenylalanine mutant virus demonstrated that VP22 was still phosphorylated but
      that the phosphorylation site may change to the C terminus rather than be in the
      N terminus as in wild-type VP22. In addition, the loss of VP22 tyrosine
      phosphorylation correlated with reduced incorporation of VP22 compared to that of
      envelope glycoprotein D in the mutant viruses but not with the amount of VP22
      produced during virus infection. Our data suggest that tyrosine phosphorylation
      of VP22 plays a role in virion assembly.

PMID- 11533165
TI  - Three herpes simplex virus type 1 latency-associated transcript mutants with
      distinct and asymmetric effects on virulence in mice compared with rabbits.
AB  - Herpes simplex virus type 1 latency-associated transcript (LAT)-null mutants have
      decreased reactivation but normal virulence in rabbits and mice. We report here
      on dLAT1.5, a mutant with LAT nucleotides 76 to 1667 deleted. Following ocular
      infection of rabbits, dLAT1.5 reactivated at a lower rate than its wild-type
      parent McKrae (6.1 versus 11.8%; P = 0.0025 [chi-square test]). Reactivation was
      restored in the marker-rescued virus dLAT1.5R (12.6%; P = 0.53 versus wild type),
      confirming the importance of the deleted region in spontaneous reactivation.
      Compared with wild-type or marker-rescued virus, dLAT1.5 had similar or slightly
      reduced virulence in rabbits (based on survival following ocular infection). In
      contrast, in mice, dLAT1.5 had increased virulence (P < 0.0001). Thus, deletion
      of LAT nucleotides 76 to 1667 increased viral virulence in mice but not in
      rabbits. In contrast, we also report here that LAT2.9A, a LAT mutant that we
      previously reported to have increased virulence in rabbits (G. C. Perng, S. M.
      Slanina, A. Yuhkt, B. S. Drolet, W. J. Keleher, H. Ghiasi, A. B. Nesburn, and S.
      L. Wechsler, J. Virol. 73:920-929, 1999), had decreased virulence in mice (P =
      0.03). In addition, we also found that dLAT371, a LAT mutant that we previously
      reported to have wild-type virulence in rabbits (G. C. Perng, S. M. Slanina, H.
      Ghiasi, A. B. Nesburn, and S. L. Wechsler, J. Virol. 70:2014-2018, 1996), had
      decreased virulence in mice (P < 0.05). Thus, these three mutants, each of which
      encodes a different LAT RNA, have different virulence phenotypes. dLAT1.5 had
      wild-type virulence in rabbits but increased virulence in mice. In contrast,
      LAT2.9A had increased virulence in rabbits but decreased virulence in mice, and
      dLAT371 had wild-type virulence in rabbits but decreased virulence in mice. Taken
      together, these results suggest that (i) the 5' end of LAT and/or a gene that
      overlaps part of this region is involved in viral virulence, (ii) this virulence
      appears to have species-specific effects, and (iii) regulation of this virulence
      may be complex.

PMID- 11533166
TI  - Recombinant herpes simplex virus type 1 expressing murine interleukin-4 is less
      virulent than wild-type virus in mice.
AB  - The effect of interleukin-4 (IL-4) on herpes simplex virus type 1 (HSV-1)
      infection in mice was evaluated by construction of a recombinant HSV-1 expressing
      the gene for murine IL-4 in place of the latency-associated transcript (LAT). The
      mutant virus (HSV-IL-4) expressed high levels of IL-4 in cultured cells. The
      replication of HSV-IL-4 in tissue culture and in trigeminal ganglia was similar
      to that of wild-type virus. In contrast, HSV-IL-4 appeared to replicate less well
      in mouse eyes and brains. Although BALB/c mice are highly susceptible to HSV-1
      infection, ocular infection with HSV-IL-4 resulted in 100% survival. Furthermore,
      57% of the mice survived coinfection with a mixture of HSV-IL-4 and a lethal dose
      of wild-type McKrae, compared with only 10% survival following infection with
      McKrae alone. Similar to wild-type BALB/c mice, 100% of IL-4(-/-) mice also
      survived HSV-IL-4 infection. T-cell depletion studies suggested that protection
      against HSV-IL-4 infection was mediated by a CD4(+)-T-cell response.

PMID- 11533167
TI  - Induction of potent immune responses by cationic microparticles with adsorbed
      human immunodeficiency virus DNA vaccines.
AB  - The effectiveness of cationic microparticles with adsorbed DNA at inducing immune
      responses was investigated in mice, guinea pigs, and rhesus macaques. Plasmid DNA
      vaccines encoding human immunodeficiency virus (HIV) Gag and Env adsorbed onto
      the surface of cationic poly(lactide-coglycolide) (PLG) microparticles were shown
      to be substantially more potent than corresponding naked DNA vaccines. In mice
      immunized with HIV gag DNA, adsorption onto PLG increased CD8(+) T-cell and
      antibody responses by approximately 100- and approximately 1,000-fold,
      respectively. In guinea pigs immunized with HIV env DNA adsorbed onto PLG,
      antibody responses showed a more rapid onset and achieved markedly higher enzyme
      linked immunosorbent assay and neutralizing titers than in animals immunized with
      naked DNA. Further enhancement of antibody responses was observed in animals
      vaccinated with PLG/DNA microparticles formulated with aluminum phosphate. The
      magnitude of anti-Env antibody responses induced by PLG/DNA particles was
      equivalent to that induced by recombinant gp120 protein formulated with a strong
      adjuvant, MF-59. In guinea pigs immunized with a combination vaccine containing
      HIV env and HIV gag DNA plasmids on PLG microparticles, substantially superior
      antibody responses were induced against both components, as measured by onset,
      duration, and titer. Furthermore, PLG formulation overcame an apparent
      hyporesponsiveness of the env DNA component in the combination vaccine. Finally,
      preliminary data in rhesus macaques demonstrated a substantial enhancement of
      immune responses afforded by PLG/DNA. Therefore, formulation of DNA vaccines by
      adsorption onto PLG microparticles is a powerful means of increasing vaccine
      potency.

PMID- 11533168
TI  - Expression of respiratory syncytial virus-induced chemokine gene networks in
      lower airway epithelial cells revealed by cDNA microarrays.
AB  - The Paramyxovirus respiratory syncytial virus (RSV) is the primary etiologic
      agent of serious epidemic lower respiratory tract disease in infants,
      immunosuppressed patients, and the elderly. Lower tract infection with RSV is
      characterized by a pronounced peribronchial mononuclear infiltrate, with
      eosinophilic and basophilic degranulation. Because RSV replication is restricted
      to airway epithelial cells, where RSV replication induces potent expression of
      chemokines, the epithelium is postulated to be a primary initiator of pulmonary
      inflammation in RSV infection. The spectrum of RSV-induced chemokines expressed
      by alveolar epithelial cells has not been fully investigated. In this report, we
      profile the kinetics and patterns of chemokine expression in RSV-infected lower
      airway epithelial cells (A549 and SAE). In A549 cells, membrane-based cDNA
      macroarrays and high-density oligonucleotide probe-based microarrays identified
      inducible expression of CC (I-309, Exodus-1, TARC, RANTES, MCP-1, MDC, and MIP-1
      alpha and -1 beta), CXC (GRO-alpha, -beta, and -gamma, ENA-78, interleukin-8 [IL
      8], and I-TAC), and CX(3)C (Fractalkine) chemokines. Chemokines not previously
      known to be expressed by RSV-infected cells were independently confirmed by
      multiprobe RNase protection assay, Northern blotting, and reverse transcription
      PCR. High-density microarrays performed on SAE cells confirmed a similar pattern
      of RSV-inducible expression of CC chemokines (Exodus-1, RANTES, and MIP-1 alpha
      and -1 beta), CXC chemokines (I-TAC, GRO-alpha, -beta, and -gamma, and IL-8), and
      Fractalkine. In contrast, TARC, MCP-1, and MDC were not induced, suggesting the
      existence of distinct genetic responses for different types of airway-derived
      epithelial cells. Hierarchical clustering by agglomerative nesting and principal
      component analyses were performed on A549-expressed chemokines; these analyses
      indicated that RSV-inducible chemokines are ordered into three related expression
      groups. These data profile the temporal changes in expression by RSV-infected
      lower airway epithelial cells of chemokines, chemotactic proteins which may be
      responsible for the complex cellular infiltrate in virus-induced respiratory
      inflammation.

PMID- 11533169
TI  - Cooperation of an RNA packaging signal and a viral envelope protein in
      coronavirus RNA packaging.
AB  - Murine coronavirus mouse hepatitis virus (MHV) produces a genome-length mRNA,
      mRNA 1, and six or seven species of subgenomic mRNAs in infected cells. Among
      these mRNAs, only mRNA 1 is efficiently packaged into MHV particles. MHV N
      protein binds to all MHV mRNAs, whereas envelope M protein interacts only with
      mRNA 1. This M protein-mRNA 1 interaction most probably determines the selective
      packaging of mRNA 1 into MHV particles. A short cis-acting MHV RNA packaging
      signal is necessary and sufficient for packaging RNA into MHV particles. The
      present study tested the possibility that the selective M protein-mRNA 1
      interaction is due to the packaging signal in mRNA 1. Regardless of the presence
      or absence of the packaging signal, N protein bound to MHV defective interfering
      RNAs and intracellularly expressed non-MHV RNA transcripts to form
      ribonucleoprotein complexes; M protein, however, interacted selectively with RNAs
      containing the packaging signal. Moreover, only the RNA that interacted
      selectively with M protein was efficiently packaged into MHV particles. Thus, it
      was the packaging signal that mediated the selective interaction between M
      protein and viral RNA to drive the specific packaging of RNA into virus
      particles. This is the first example for any RNA virus in which a viral envelope
      protein and a known viral RNA packaging signal have been shown to determine the
      specificity and selectivity of RNA packaging into virions.

PMID- 11533170
TI  - Protection against woodchuck hepatitis virus (WHV) infection by gene gun
      coimmunization with WHV core and interleukin-12.
AB  - Woodchuck hepatitis virus (WHV) and hepatitis B virus (HBV) are closely similar
      with respect to genomic organization, host antiviral responses, and pathobiology
      of the infection. T-cell immunity against viral nucleocapsid (HBcAg or WHcAg) has
      been shown to play a critical role in viral clearance and protection against
      infection. Here we show that vaccination of healthy woodchucks by gene gun
      bombardment with a plasmid coding for WHcAg (pCw) stimulates proliferation of
      WHcAg-specific T cells but that these cells do not produce significant levels of
      gamma interferon (IFN-gamma) upon antigen stimulation. In addition, animals
      vaccinated with pCw alone were not protected against WHV inoculation. In order to
      induce a Th1 cytokine response, another group of woodchucks was immunized with
      pCw together with another plasmid coding for woodchuck interleukin-12 (IL-12).
      These animals exhibited WHcAg-specific T-cell proliferation with high IFN-gamma
      production and were protected against challenge with WHV, showing no viremia or
      low-level transient viremia after WHV inoculation. In conclusion, gene gun
      immunization with WHV core generates a non-Th1 type of response which does not
      protect against experimental infection. However, steering the immune response to
      a Th1 cytokine profile by IL-12 coadministration achieves protective immunity.
      These data demonstrate a crucial role of Th1 responses in the control of
      hepadnavirus replication and suggest new approaches to inducing protection
      against HBV infection.

PMID- 11533171
TI  - A novel nonnucleoside inhibitor specifically targets cytomegalovirus DNA
      maturation via the UL89 and UL56 gene products.
AB  - 3-Hydroxy-2,2-dimethyl-N-[4([[5-(dimethylamino)-1-naphthyl]sulfonyl]amino)
      phenyl]propanamide (BAY 38-4766) is a novel selective nonnucleoside inhibitor of
      cytomegalovirus (CMV) replication with an excellent safety profile. This compound
      and structural analogues inhibit neither viral DNA synthesis nor viral
      transcription and translation. Accumulation of dense bodies and noninfectious
      enveloped particles coincides with inhibition of both concatemer processing and
      functional cleavage at intergenomic transitions, pointing to interference with
      viral DNA maturation and packaging of monomeric genome lengths. Resistant virus
      populations, including a murine CMV (MCMV) isolate with 566-fold-decreased drug
      sensitivity, were selected in vitro. Sequencing of the six open reading frames
      (ORFs) known to be essentially involved in viral DNA cleavage and packaging
      identified mutations in ORFs UL56, UL89, and UL104. Construction of MCMV
      recombinants expressing different combinations of murine homologues of mutant
      UL56, UL89, and UL104 and analysis of drug susceptibilities clearly demonstrated
      that mutant ORFs UL89 exon II (M360I) and M56 (P202A I208N) individually confer
      resistance to BAY 38-4766. A combination of both mutant proteins exhibited a
      strong synergistic effect on resistance, reconstituting the high-resistance
      phenotype of the in vitro mutant. These findings are consistent with genetic
      mapping of resistance to TCRB (2,5,6-trichloro-1-beta-D-ribofuranosyl
      benzimidazole) (P. M. Krosky et al., J. Virol. 72:4721-4728, 1998) and provide
      further indirect evidence that proteins encoded by UL89 and UL56 function as two
      subunits of the CMV terminase. While these studies also suggest that the
      molecular mechanism of BAY 38-4766 is distinct from that of benzimidazole
      ribonucleosides, they also offer an explanation for the excellent specificity and
      tolerability of BAY 38-4766, since mammalian DNA does not undergo comparable
      maturation steps.

PMID- 11533172
TI  - The conserved serine 177 in the delta antigen of hepatitis delta virus is one
      putative phosphorylation site and is required for efficient viral RNA
      replication.
AB  - Hepatitis delta virus (HDV) small delta antigen (S-HDAg) plays a critical role in
      virus replication. We previously demonstrated that the S-HDAg phosphorylation
      occurs on both serine and threonine residues. However, their biological
      significance and the exact phosphorylation sites of S-HDAg are still unknown. In
      this study, phosphorylated S-HDAg was detected only in the intracellular
      compartment, not in viral particles. In addition, the number of phosphorylated
      isoforms of S-HDAg significantly increased with the extent of viral replication
      in transfection system. Site-directed mutagenesis showed that alanine replacement
      of serine 177, which is conserved among all the known HDV strains, resulted in
      reduced phosphorylation of S-HDAg, while the mutation of the other two conserved
      serine residues (2 and 123) had little effect. The S177A mutant dramatically
      decreased its capability in assisting HDV RNA replication, with a preferential
      and profound impairment of the antigenomic RNA replication. Furthermore, the
      viral RNA editing, a step relying upon antigenomic RNA replication, was also
      abolished by this mutation. These results suggested that phosphorylation of S
      HDAg, with serine 177 as a presumable site, plays a critical role in viral RNA
      replication, especially in augmenting the replication of antigenomic RNA.

PMID- 11533173
TI  - Receptor binding transforms the surface subunit of the mammalian C-type
      retrovirus envelope protein from an inhibitor to an activator of fusion.
AB  - The envelope protein (Env) of murine leukemia viruses (MLVs) is composed of a
      surface subunit (SU) and a transmembrane subunit (TM), which mediates membrane
      fusion, resulting in infection. SU contains a discrete N-terminal receptor
      binding domain (RBD) that is connected to the remainder of Env by a short,
      proline-rich segment. Previous studies suggest that after receptor binding, the
      RBD interacts directly with the remainder of Env to trigger fusion (A. L.
      Barnett, R. A. Davey, and J. M. Cunningham, Proc. Natl. Acad. Sci. USA 98:4113
      4118, 2001). To investigate the role of the RBD in activating fusion, we compared
      infection by several MLVs that are defective unless rescued in trans by the
      addition of soluble RBD to the culture medium. Infection by MLV lacking a
      critical histidine residue near the N terminus of the viral RBD is dependent on
      the expression of receptors for both the RBD in the viral Env and the soluble RBD
      supplied in trans. However, infection by MLVs in which the RBD has been deleted
      or replaced by the ligand erythropoietin are dependent only on expression of the
      receptor for the soluble RBD. We were able to expand the host range of xenotropic
      MLV to nonpermissive murine fibroblasts only if the RBD was deleted from the
      xenotropic viral envelope and the soluble RBD from ecotropic Friend MLV was
      supplied to the culture medium. These findings indicate that receptor binding
      transforms the RBD from an inhibitor to an activator of the viral fusion
      mechanism and that viruses lacking the critical histidine residue at the N
      terminus of the RBD are impaired at the activation step.

PMID- 11533174
TI  - Virion association of IE62, the varicella-zoster virus (VZV) major
      transcriptional regulatory protein, requires expression of the VZV open reading
      frame 66 protein kinase.
AB  - IE62, the major transcriptional regulatory protein encoded by varicella-zoster
      virus (VZV), is associated with the tegument of gradient-purified virions. Here,
      we show that most, if not all, of the association requires the expression of open
      reading frame 66 (ORF66), a protein kinase. The association of IE62 with wild
      type VZV virions was confirmed using immunoelectron microscopy with IE62-specific
      antibodies, which reacted with virions in ultrathin sections of VZV-infected
      cells. Fractionated purified virions from cells infected with recombinant VZV
      ROka contained substantial levels of the 175-kDa virion IE62 protein and also
      contained the ORF66 protein. However, virions from cells infected with
      recombinant VZV ROka66S, in which ORF66 is disrupted, lacked not only the ORF66
      protein but also most of the virion 175-kDa IE62 polypeptide. The virion
      associated protein kinase activity was still present in ROka66S virions, although
      the 175-kDa protein substrate for the virion kinase was absent, implying that the
      virion protein kinase is encoded by genes other than ORF66. The very low levels
      of IE62 in ROka66S virions indicate that ORF66 protein mediates the
      redistribution of IE62 to sites of tegument assembly. IE62 was resolved into
      several species from VZV-infected cells which showed mobility differences between
      ROka and ROka66S, and a specific form of IE62 was detected in ROka virions. These
      results are consistent with a role for the ORF66-mediated phosphorylation of IE62
      that results in cytoplasmic distribution of the regulatory protein for tegument
      inclusion. They support a model in which VZV tegument acquisition occurs in the
      cytoplasm. As such, two unusual features of VZV IE62, namely, its virion
      inclusion and its phosphorylation and nuclear exclusion by the ORF66 protein
      kinase, are functionally linked.

PMID- 11533175
TI  - A cucumber mosaic virus (CMV) RNA 1 transgene mediates suppression of the
      homologous viral RNA 1 constitutively and prevents CMV entry into the phloem.
AB  - Resistance to Cucumber mosaic virus (CMV) in tobacco lines transformed with CMV
      RNA 1 is characterized by reduced virus accumulation in the inoculated leaf, with
      specific suppression of accumulation of the homologous viral RNA 1, and by the
      absence of systemic infection. We show that the suppression of viral RNA 1 occurs
      in protoplasts from resistant transgenic plants and therefore is not due to a
      host response activated by the cell-to-cell spread of virus. In contrast,
      suppression of Tobacco rattle virus vectors carrying CMV RNA 1 sequences did not
      occur in protoplasts from resistant plants. Furthermore, steady-state levels of
      transgene mRNA 1 were higher in resistant than in susceptible lines. Thus, the
      data indicate that sequence homology is not sufficient to induce suppression.
      Grafting experiments using transgenic resistant or susceptible rootstocks and
      scions demonstrated that the resistance mechanism exhibited an additional barrier
      to phloem entry, preventing CMV from moving a long distance in resistant plants.
      On the other hand, virus from susceptible rootstocks could systemically infect
      grafted resistant scions via the phloem. Analysis of viral RNA accumulation in
      the infected scions showed that the mechanism that suppresses the accumulation of
      viral RNA 1 at the single-cell level was overcome. The data indicate that this
      transgene-mediated systemic resistance probably is not based on a
      posttranscriptional gene-silencing mechanism.

PMID- 11533176
TI  - Rescue of rabies virus from cloned cDNA and identification of the pathogenicity
      related gene: glycoprotein gene is associated with virulence for adult mice.
AB  - In order to identify the viral gene related to the pathogenicity of rabies virus,
      we tried to establish a reverse genetics system of the attenuated RC-HL strain,
      which causes nonlethal infection in adult mice after intracerebral inoculation. A
      full-length genome plasmid encoding the complete antigenomic cDNA of the RC-HL
      strain and helper plasmids containing cDNAs of the complete open reading frame of
      the N, P, and L genes, respectively, were constructed. After transfection of
      these plasmids into BHK-21 cells infected with the T7 RNA polymerase-expressing
      vaccinia virus, infectious rabies virus with almost the same biological
      properties as those of the wild-type RC-HL strain was rescued. Using this reverse
      genetics system of the RC-HL strain, we generated a chimeric virus with the open
      reading frame of the glycoprotein gene from the parent Nishigahara strain, which
      kills adult mice after intracerebral inoculation, in the background of the RC-HL
      genome. Since the chimeric virus killed adult mice following intracerebral
      inoculation, it became evident that the open reading frame of the glycoprotein
      gene is related to the pathogenicity of the Nishigahara strain for adult mice.

PMID- 11533177
TI  - Epstein-Barr virus LMP-1 natural sequence variants differ in their potential to
      activate cellular signaling pathways.
AB  - The latent membrane protein 1 (LMP-1) oncogene of Epstein-Barr virus (EBV) is
      believed to contribute to the development of many EBV-associated tumors, and
      there is evidence that sequence variation can affect some functions of LMP-1.
      Most studies have been restricted to the prototype B95.8 LMP-1 gene and genes
      isolated from EBV of nasopharyngeal carcinoma (NPC) patients. Here, we analyzed
      the signaling functions of LMP-1 from a panel of nine EBV isolates, including
      representatives of four defined groups of European LMP-1 variants (groups A to D
      [K. Sandvej, J. W. Gratama, M. Munch, X. G. Zhou, R. L. Bolhuis, B. S. Andresen,
      N. Gregersen, and S. Hamilton-Dutoit, Blood 90:323-330, 1997]) and Chinese NPC
      derived LMP-1. Chinese and group D variants activated the transcription factor NF
      kappa B two- to threefold more efficiently than B95.8 LMP-1, while Chinese, group
      B, and group D variants similarly activated activator protein 1 (AP-1)
      transcription more efficiently than did B95.8 LMP-1. However, there were no amino
      acid substitutions in the core binding regions for tumor necrosis factor receptor
      associated adapter proteins known to mediate NF-kappa B and AP-1 activation. In
      contrast, despite sequence variation in the proposed Janus kinase 3 binding
      region, STAT activation was remarkably constant among the panel of LMP-1
      variants. Analysis of the induction of CD54 (intercellular adhesion molecule 1)
      protein expression by the LMP-1 variants showed differences that did not
      correlate with either NF-kappa B or AP-1. Therefore, while the defined sequence
      variant groups do correlate with LMP-1 function, the results highlight the fact
      that the relationship between sequence variation and signaling function is
      extremely complex. It appears unlikely that one particular amino acid
      substitution or deletion will define a disease-associated variant of LMP-1.

PMID- 11533178
TI  - Induction of p53-independent apoptosis by simian virus 40 small t antigen.
AB  - Simian virus 40 small t antigen (st) is required for optimal transformation and
      replication properties of the virus. We find that in certain cell types, such as
      the human osteosarcoma cell line U2OS, st is capable of inducing apoptosis, as
      evidenced by a fragmented nuclear morphology and positive terminal
      deoxynucleotidyltransferase-mediated dUTP nick end labeling staining of
      transfected cells. The cell death can be p53 independent, since it also occurs in
      p53-deficient H1299 cells. Genetic analysis indicates that two specific mutants
      affect apoptosis induction. One of these (C103S) has been frequently used as a
      PP2A binding mutant. The second mutant (TR4) lacks the final four amino acids of
      st, which have been reported to be unimportant for PP2A binding in vitro.
      However, TR4 unexpectedly fails to bind PP2A in vivo. Furthermore, a long-term
      colony assay reveals a potent colony inhibition upon st expression, and the
      behavior of st mutants in this assay reflects the relative frequency of nuclear
      fragmentation observed in transfections using the same mutants. Notably, either
      Bcl-2 coexpression or broad caspase inhibitor treatment could restore normal
      nuclear morphology. Finally, fluorescence-activated cell sorting analysis
      suggests a correlation between the ability of st to modulate cell cycle
      progression and apoptosis. Taken together, these observations underscore that st
      does not always promote proliferation but may, depending on conditions and cell
      type, effect a cell death response.

PMID- 11533179
TI  - Proteolytic processing of the p2/nucleocapsid cleavage site is critical for human
      immunodeficiency virus type 1 RNA dimer maturation.
AB  - Differences in virion RNA dimer stability between mature and protease-defective
      (immature) forms of human immunodeficiency virus type 1 (HIV-1) suggest that
      maturation of the viral RNA dimer is regulated by the proteolytic processing of
      the HIV-1 Gag and Gag-Pol precursor proteins. However, the proteolytic processing
      of these proteins occurs in several steps denoted primary, secondary, and
      tertiary cleavage events and, to date, the processing step associated with
      formation of stable HIV-1 RNA dimers has not been identified. We show here that a
      mutation in the primary cleavage site (p2/nucleocapsid [NC]) hinders formation of
      stable virion RNA dimers, while dimer stability is unaffected by mutations in the
      secondary (matrix/capsid [CA], p1/p6) or a tertiary cleavage site (CA/p2). By
      introducing mutations in a shared cleavage site of either Gag or Gag-Pol, we also
      show that the cleavage of the p2/NC site in Gag is more important for dimer
      formation and stability than p2/NC cleavage in Gag-Pol. Electron microscopy
      analysis of viral particles shows that mutations in the primary cleavage site in
      Gag but not in Gag-Pol inhibit viral particle maturation. We conclude that virion
      RNA dimer maturation is dependent on proteolytic processing of the primary
      cleavage site and is associated with virion core formation.

PMID- 11533180
TI  - High resistance of human parainfluenza type 2 virus protein-expressing cells to
      the antiviral and anti-cell proliferative activities of alpha/beta interferons:
      cysteine-rich V-specific domain is required for high resistance to the
      interferons.
AB  - Human parainfluenza type 2 virus (hPIV-2)-infected HeLa (HeLa-CA) cells and hPIV
      2 V-expressing HeLa (HeLa-V) cells show high resistance to alpha/beta interferons
      (IFN-alpha/beta) irrespective of whether vesicular stomatitis virus or Sindbis
      virus is used as a challenge virus. When Sindbis virus is used, these cells show
      high susceptibility to human IFN-gamma. Furthermore, the multiplication of HeLa-V
      cells is not inhibited by IFN-alpha/beta. HeLa cells expressing the N-terminally
      truncated V protein show resistance to IFN-alpha/beta, showing that the IFN
      resistance determinant maps to the cysteine-rich V-specific domain. A complete
      defect of Stat2 is found in HeLa-CA and HeLa-V cells, whereas the levels of Stat1
      expression are not significantly different among HeLa, HeLa-CA, HeLa-P, and HeLa
      V cells, indicating that IFN-alpha/beta resistance of HeLa-CA and HeLa-V cells is
      due to a defect of Stat2. HeLa-SV41V cells show high resistance to all IFNs, and
      no expression of Stat1 can be detected. Stat2 mRNA is fully detected in HeLa-V
      cells. Stat2 was scarcely pulse-labeled in the HeLa-V cells, indicating that
      synthesis of Stat2 is suppressed or Stat2 is very rapidly degraded in HeLa-V
      cells. The V protein suppresses the in vitro translation of Stat2 mRNA more
      extensively than that of Stat1 mRNA. An extremely small amount of Stat2 can be
      detected in HeLa-V cells treated with proteasome inhibitors. The half-life of
      Stat2 is approximately 3.5 and 2 h in uninfected and hPIV-2-infected HeLa cells,
      respectively. This study shows that synthesis of Stat2 may be suppressed and
      Stat2 degradation is also enhanced in hPIV-2-infected HeLa and HeLa-V cells.

PMID- 11533181
TI  - Additive effects characterize the interaction of antibodies involved in
      neutralization of the primary dualtropic human immunodeficiency virus type 1
      isolate 89.6.
AB  - Human immunodeficiency virus-type I (HIV-1) infection elicits antibodies (Abs)
      directed against several regions of the gp120 and gp41 envelope glycoproteins.
      Many of these Abs are able to neutralize T-cell-line-adapted strains (TCLA) of
      HIV-1, but only a few effectively neutralize primary HIV-1 isolates. The nature
      of HIV-1 neutralization has been carefully studied using human monoclonal Abs
      (MAbs), and the ability of such MAbs to act in synergy to neutralize HIV-1 has
      also been extensively studied. However, most synergy studies have been conducted
      using TCLA strains. To determine the nature of Ab interaction in HIV-1 primary
      isolate neutralization, a panel of 12 anti-HIV-1 human immunoglobulin G (IgG)
      MAbs, specific for epitopes in gp120 and gp41, were used. Initial tests showed
      that six of these MAbs, as well as sCD4, used individually, were able to
      neutralize the dualtropic primary isolate HIV-1(89.6); MAbs giving significant
      neutralization at 2 to 10 microg/ml included 2F5 (anti-gp41), 50-69 (anti-gp41),
      IgG1b12 (anti-gp120(CD4bd)), 447-52D (anti-gp120(V3)), 2G12 (anti-gp120), and 670
      D (anti-gp120(C5)). For studies of reagent interaction, 16 binary combinations of
      reagents were tested for their ability to neutralize HIV-1(89.6). Reagent
      combinations tested included one neutralizing MAb with sCD4, six pairs consisting
      of two neutralizing MAbs, and nine pairs consisting of one neutralizing MAb with
      another non-neutralizing MAb. To assess the interaction of the latter type of
      combination, a new mathematical treatment of reagent interaction was developed
      since previously used methods could be used only when both reagents neutralize.
      Synergy was noted between sCD4 and a neutralizing anti-gp120(V3) MAb. Antagonism
      was noted between two pairs of anti-gp41 MAbs (one neutralizing and one non
      neutralizing). All of the other 13 pairs of MAbs tested displayed only additive
      effects. These studies suggest that Abs rarely act in synergy to neutralize
      primary isolate HIV-1(89.6); many anti-HIV-1 Abs act additively to mediate this
      biological function.

PMID- 11533182
TI  - Syndecans serve as attachment receptors for human immunodeficiency virus type 1
      on macrophages.
AB  - Macrophages are thought to represent one of the first cell types in the body to
      be infected during the early stage of human immunodeficiency virus type 1 (HIV-1)
      transmission and represent a potential viral reservoir in vivo. Thus, an
      understanding of HIV-1 attachment to these cells is fundamental to the
      development of novel anti-HIV-1 therapies. Although one of the major targets of
      HIV-1 in vivo--CD4(+) T lymphocytes--express high CD4 levels, other major targets
      such as macrophages do not. We asked in this study whether this low CD4 level on
      macrophages is sufficient to support HIV-1 attachment to these cells or whether
      cell surface proteins other than CD4 are required for this process. We show that
      CD4 alone is not sufficient to support the initial adsorption of HIV-1 to
      macrophages. Importantly, we find that heparan sulfate proteoglycans (HSPGs)
      serve as the main class of attachment receptors for HIV-1 on macrophages. Most
      importantly, we demonstrate that a single family of HSPGs, the syndecans,
      efficiently mediates HIV-1 attachment and represents an abundant class of
      attachment receptors on macrophages.

PMID- 11533183
TI  - Enhancement of capsid gene expression: preparing the human papillomavirus type 16
      major structural gene L1 for DNA vaccination purposes.
AB  - Expression of the structural proteins L1 and L2 of the human papillomaviruses
      (HPV) is tightly regulated. As a consequence, attempts to express these prime
      candidate genes for prophylactic vaccination against papillomavirus-associated
      diseases in mammalian cells by means of simple DNA transfections result in
      insufficient production of the viral antigens. Similarly, in vivo DNA vaccination
      using HPV L1 or L2 expression constructs produces only weak immune responses. In
      this study we demonstrate that transient expression of the HPV type 16 L1 and L2
      proteins can be highly improved by changing the RNA coding sequence, resulting in
      the accumulation of significant amounts of virus-like particles in the nuclei of
      transfected cells. Data presented indicate that, in the case of L1, adaptation
      for codon usage accounts for the vast majority of the improvement in protein
      expression, whereas translation-independent posttranscriptional events contribute
      only to a minor degree. Finally, the adapted L1 genes demonstrate strongly
      increased immunogenicity in vivo compared to that of unmodified L1 genes.

PMID- 11533184
TI  - Identification of human immunodeficiency virus type 1 subtype C Gag-, Tat-, Rev-,
      and Nef-specific elispot-based cytotoxic T-lymphocyte responses for AIDS vaccine
      design.
AB  - The most severe human immunodeficiency virus type 1 (HIV-1) epidemic is occurring
      in southern Africa. It is caused by HIV-1 subtype C (HIV-1C). In this study we
      present the identification and analysis of cumulative cytotoxic T-lymphocyte
      (CTL) responses in the southern African country of Botswana. CTLs were shown to
      be an important component of the immune response to control HIV-1 infection. The
      definition of optimal and dominant epitopes across the HIV-1C genome that are
      targeted by CTL is critical for vaccine design. The characteristics of the
      predominant virus that causes the HIV-1 epidemic in a certain geographic area and
      also the genetic background of the population, through the distribution of common
      HLA class I alleles, might impact dominant CTL responses in the vaccinee and in
      the general population. The enzyme-linked immunospot (Elispot) gamma interferon
      assay has recently been shown to be a reliable tool to map optimal CTL epitopes,
      correlating well with other methods, such as intracellular staining, tetramer
      staining, and the classical chromium release assay. Using Elispot with
      overlapping synthetic peptides across Gag, Tat, Rev, and Nef, we analyzed HIV-1C
      specific CTL responses of HIV-1-infected blood donors. Profiles of cumulative
      Elispot-based CTL responses combined with diversity and sequence consensus data
      provide an additional characterization of immunodominant regions across the HIV
      1C genome. Results of the study suggest that the construction of a poly-epitope
      subtype-specific HIV-1 vaccine that includes multiple copies of immunodominant
      CTL epitopes across the viral genome, derived from predominant HIV-1 viruses,
      might be a logical approach to the design of a vaccine against AIDS.

PMID- 11533185
TI  - Protective immunity and antibody-secreting cell responses elicited by combined
      oral attenuated Wa human rotavirus and intranasal Wa 2/6-VLPs with mutant
      Escherichia coli heat-labile toxin in gnotobiotic pigs.
AB  - Two combined rotavirus vaccination regimens were evaluated in a gnotobiotic pig
      model of rotavirus infection and disease and were compared to previously tested
      rotavirus vaccination regimens. The first (AttHRV/VLP2x) involved oral
      inoculation with one dose of attenuated (Att) Wa human rotavirus (HRV), followed
      by two intranasal (i.n.) doses of a rotavirus-like particle (2/6-VLPs) vaccine
      derived from Wa (VP6) and bovine RF (VP2) rotavirus strains. The 2/6-VLPs were
      coadministered with a mutant Escherichia coli heat-labile toxin, LT-R192G (mLT)
      adjuvant. For the second regimen (VLP2x/AttHRV), two i.n. doses of 2/6-VLPs+mLT
      were given, followed by one oral dose of attenuated Wa HRV. To compare the
      protective efficacy and immune responses induced by the combined vaccine regimens
      with individual rotavirus vaccine regimens, we included in the experiments the
      following vaccine groups: one oral dose of attenuated Wa HRV (AttHRV1x and
      Mock2x/AttHRV, respectively), three oral doses of attenuated Wa HRV (AttHRV3x),
      three i.n. doses of 2/6-VLPs plus mLT (VLP3x), three i.n. doses of purified
      double-layered inactivated Wa HRV plus mLT (InactHRV3x), mLT alone, and mock
      inoculated pigs. The isotype, magnitude, and tissue distribution of antibody
      secreting cells (ASCs) in the intestinal and systemic lymphoid tissues were
      evaluated using an enzyme-linked immunospot assay. The AttHRV/VLP2x regimen
      stimulated the highest mean numbers of intestinal immunoglobulin A (IgA) ASCs
      prechallenge among all vaccine groups. This regimen induced partial protection
      against virus shedding (58%) and diarrhea (44%) upon challenge of pigs with
      virulent Wa HRV. The reverse VLP2x/AttHRV regimen was less efficacious than the
      AttHRV/VLP2x regimen in inducing IgA ASC responses and protection against
      diarrhea (25% protection rate) but was more efficacious than VLP3x or InactHRV3x
      (no protection). In conclusion, the AttHRV/VLP2x vaccination regimen stimulated
      the strongest B-cell responses in the intestinal mucosal immune system at
      challenge and conferred a moderately high protection rate against rotavirus
      disease, indicating that priming of the mucosal inductive site at the portal of
      natural infection with a replicating vaccine, followed by boosting with a
      nonreplicating vaccine at a second mucosal inductive site, may be a highly
      effective approach to stimulate the mucosal immune system and induce protective
      immunity against various mucosal pathogens.

PMID- 11533186
TI  - Comparative pathogenesis of tissue culture-adapted and wild-type Cowden porcine
      enteric calicivirus (PEC) in gnotobiotic pigs and induction of diarrhea by
      intravenous inoculation of wild-type PEC.
AB  - Porcine enteric calicivirus (PEC/Cowden) causes diarrhea in pigs, grows in cell
      culture, and is morphologically and genetically similar to the Sapporo-like human
      caliciviruses. Genetic analysis revealed that the tissue culture-adapted (TC)
      Cowden PEC has one distant and three clustered amino acid substitutions in the
      capsid region and 2 amino acid changes in the RNA polymerase region compared to
      wild-type (WT) PEC (M. Guo, K.-O. Chang, M. E. Hardy, Q. Zhang, A. V. Parwani,
      and L. J. Saif, J. Virol. 73:9625-9631, 1999). In this study, the TC PEC,
      passaged in a porcine kidney cell line, and the WT PEC, passaged in gnotobiotic
      (Gn) pigs, were used to orally inoculate 13 4- to 6-day-old Gn pigs. No diarrhea
      developed in the TC-PEC-exposed pigs, whereas moderate diarrhea developed in the
      WT-PEC orally inoculated pigs, persisting for 2 to 5 days. Fecal virus shedding
      persisting for at least 7 days was detected by both reverse transcription (RT)
      PCR and antigen-enzyme-linked immunosorbent assay (antigen-ELISA) in both TC-PEC
      and WT-PEC orally inoculated pigs but not in mock-inoculated pigs. The PEC
      particles were detected by immunoelectron microscopy (IEM) in intestinal contents
      from all the WT-PEC-inoculated pigs, but not from the TC-PEC-inoculated pigs.
      Mild (duodenum and jejunum) or no (ileum) villous atrophy was observed in
      histologic sections of the small intestines of TC-PEC-inoculated pigs, whereas WT
      PEC caused mild to severe (duodenum and jejunum) villous atrophy and fusion.
      Scanning electron microscopy confirmed mild shortening and blunting of villi in
      the duodenum and jejunum of the TC-PEC-inoculated pigs, in contrast to moderate
      to severe villous shortening and blunting in the duodenum and jejunum of WT-PEC
      inoculated pigs. Higher numbers of PEC antigen-positive villous enterocytes were
      detected by immunofluorescent (IF) staining in the proximal small intestine of
      the WT-PEC-inoculated pigs, in contrast to low numbers of PEC antigen-positive
      enterocytes in only one of four TC-PEC-inoculated pigs. No PEC antigen-positive
      cells were observed in the colon or extraintestinal tissues of all inoculated
      pigs or in the small intestine of one mock-inoculated pig. Thus, the TC PEC was
      at least partially attenuated (no diarrhea, mild lesions) after serial passage in
      cell culture. In further experiments, three 4- to 6-day-old Gn pigs were
      intravenously (i.v.) inoculated with WT PEC, and all pigs developed diarrhea and
      villous atrophy in the small intestines resembling that observed in the orally
      inoculated pigs. Fecal viral shedding persisting for 8 days was detected by both
      RT-PCR and antigen-ELISA, and PEC was detected by IEM in feces or intestinal
      contents. The PEC RNA and antigens (at low titers) were detected in acute-phase
      sera from all the WT-PEC i.v.-inoculated pigs and also from seven of nine of the
      WT-PEC orally inoculated pigs. Oral or i.v. inoculation of four additional pigs
      with the PEC-positive acute-phase sera induced diarrhea, small intestinal
      lesions, PEC shedding in feces, and seroconversion to PEC, confirming the
      occurrence of viremia during PEC infection, with infectious PEC present in acute
      phase sera. No diarrhea, histopathologic changes, or IF staining in the small
      intestine or fecal or serum detection of PEC was evident in two pigs i.v. mock
      inoculated or a pig inoculated i.v. with inactivated WT PEC. To our knowledge,
      this is the first report of an attenuated enteric calicivirus, the induction of
      diarrhea, and intestinal lesions in Gn pigs caused by i.v. inoculation of WT PEC
      and the presence of viremia following PEC infection.

PMID- 11533187
TI  - Downregulation of p56(lck) tyrosine kinase activity in T cells of squirrel
      monkeys (Saimiri sciureus) correlates with the nontransforming and apathogenic
      properties of herpesvirus saimiri in its natural host.
AB  - Herpesvirus saimiri is capable of transforming T lymphocytes of various primate
      species to stable growth in culture. The interaction of the T-cellular tyrosine
      kinase p56(lck) with the transformation-associated viral protein Tip has been
      shown before to activate the kinase and provides one model for the T-cell
      specific transformation by herpesvirus saimiri subgroup C strains. In contrast to
      other primate species, squirrel monkeys (Saimiri sciureus) are naturally infected
      with the virus without signs of lymphoma or other disease. Although the
      endogenous virus was regularly recovered from peripheral blood cells from
      squirrel monkeys, we observed that the T cells lost the virus genomes in culture.
      Superinfection with virus strain C488 did not induce growth transformation, in
      contrast to parallel experiments with T cells of other primate species.
      Surprisingly, p56(lck) was enzymatically inactive in primary T-cell lines derived
      from different squirrel monkeys, although the T cells reacted appropriately to
      stimulatory signals. The cDNA sequence revealed minor point mutations only, and
      transfections in COS-7 cells demonstrated that the S. sciureus lck gene codes for
      a functional enzyme. In S. sciureus, the tyrosine kinase p56(lck) was not
      activated after T-cell stimulation and enzymatic activity could not be induced by
      Tip of herpesvirus saimiri C488. However, the suppression of p56(lck) was
      partially released after administration of the phosphatase inhibitor pervanadate.
      This argues for unique species-specific conditions in T cells of S. sciureus
      which may interfere with the transforming activity and pathogenicity of
      herpesvirus saimiri subgroup C strains in their natural host.

PMID- 11533188
TI  - Function of Rta is essential for lytic replication of murine gammaherpesvirus 68.
AB  - Rta, encoded primarily by open reading frame 50, is well conserved among
      gammaherpesviruses. It has been shown that the Rta proteins of Epstein Barr virus
      (EBV), Kaposi's sarcoma-associated herpesvirus (KSHV, or HHV-8), and murine
      gammaherpesvirus 68 (MHV-68; also referred to as gamma HV68) play an important
      role in viral reactivation from latency. However, the role of Rta during
      productive de novo infection has not been characterized in gammaherpesviruses.
      Since there are cell lines that can support efficient productive de novo
      infection by MHV-68 but not EBV or KSHV, we examined whether MHV-68 Rta plays a
      role in initiating viral lytic replication in productively infected cells. Rta,
      functioning as a transcriptional activator, can activate the viral promoter of
      early lytic genes. The amino acid sequence alignments of the Rta homologues
      suggest that the organizations of their functional domains are similar, with the
      DNA binding and dimerization domains at the N terminus and the trans-activation
      domain at the C terminus. We constructed two mutants of MHV-68 Rta, Rd1 and Rd2,
      with deletions of 112 and 243 amino acids from the C terminus, respectively. Rd1
      and Rd2 could no longer trans-activate the promoter of MHV-68 gene 57, consistent
      with the deletions of their trans-activation domains at the C terminus.
      Furthermore, Rd1 and Rd2 were able to function as dominant-negative mutants,
      inhibiting trans-activation of wild-type Rta. To study whether Rd1 and Rd2
      blocked viral lytic replication, purified virion DNA was cotransfected with Rd1
      or Rd2 into fibroblasts. Expression of viral lytic proteins was greatly
      suppressed, and the yield of infectious viruses was reduced up to 10(4)-fold.
      Stable cell lines constitutively expressing Rd2 were established and infected
      with MHV-68. Transcription of the immediate-early gene, rta, and the early gene,
      tk, of the virus was reduced in these cell lines. The presence of Rd2 also led to
      attenuation of viral lytic protein expression and virion production. The ability
      of Rta dominant-negative mutants to inhibit productive infection suggests that
      the trans-activation function of Rta is essential for MHV-68 lytic replication.
      We propose that a single viral protein, Rta, governs the initiation of MHV-68
      lytic replication during both reactivation and productive de novo infection.

PMID- 11533189
TI  - Evidence that Equine rhinitis A virus VP1 is a target of neutralizing antibodies
      and participates directly in receptor binding.
AB  - Equine rhinitis A virus (ERAV) is a respiratory pathogen of horses and is
      classified as an Aphthovirus, the only non-Foot-and-mouth disease virus (FMDV)
      member of this genus. In FMDV, virion protein 1 (VP1) is a major target of
      protective antibodies and is responsible for viral attachment to permissive cells
      via an RGD motif located in a distal surface loop. Although both viruses share
      considerable sequence identity, ERAV VP1 does not contain an RGD motif. To
      investigate antibody and receptor-binding properties of ERAV VP1, we have
      expressed full-length ERAV VP1 in Escherichia coli as a glutathione S-transferase
      (GST) fusion protein (GST-VP1). GST-VP1 reacted specifically with antibodies
      present in serum from a rabbit immunized with purified ERAV virions and also in
      convalescent-phase sera from horses experimentally infected with ERAV. An
      antiserum raised in rabbits to GST-VP1 reacted strongly with viral VP1 and
      effectively neutralized ERAV infection in vitro. Using a flow cytometry-based
      binding assay, we found that GST-VP1, but not other GST fusion proteins, bound to
      cell surface receptors. This binding was reduced in a dose-dependent manner by
      the addition of purified ERAV virions, demonstrating the specificity of this
      interaction. A separate cell-binding assay also implicated GST-VP1 in receptor
      binding. Importantly, anti-GST-VP1 antibodies inhibited the binding of ERAV
      virions to Vero cells, suggesting that these antibodies exert their neutralizing
      effect by blocking viral attachment. Thus ERAV VP1, like its counterpart in FMDV,
      appears to be both a target of protective antibodies and involved directly in
      receptor binding. This study reveals the potential of recombinant VP1 molecules
      to serve as vaccines and diagnostic reagents for the control of ERAV infections.

PMID- 11533190
TI  - Rescue of recombinant Thogoto virus from cloned cDNA.
AB  - Thogoto virus (THOV) is a tick-transmitted orthomyxovirus with a genome
      consisting of six negative-stranded RNA segments. To rescue a recombinant THOV,
      the viral structural proteins were produced from expression plasmids by means of
      a vaccinia virus expressing the T7 RNA polymerase. Genomic virus RNAs (vRNAs)
      were generated from plasmids under the control of the RNA polymerase I promoter.
      Using this system, we could efficiently recover recombinant THOV following
      transfection of 12 plasmids into 293T cells. To verify the recombinant nature of
      the rescued virus, specific genetic tags were introduced into two vRNA segments.
      The availability of this efficient reverse genetics system will allow us to
      address hitherto-unanswered questions regarding the biology of THOV by
      manipulating viral genes in the context of infectious virus.

PMID- 11533191
TI  - Evidence for similar recognition of the conserved neutralization epitopes of
      human immunodeficiency virus type 1 envelope gp120 in humans and macaques.
AB  - We compared the immune responses to the human immunodeficiency virus type 1 (HIV
      1) envelope glycoproteins in humans and macaques with the use of clade A and
      clade B isogenic V3 loop glycan-possessing and -deficient viruses. We found that
      the presence or absence of the V3 loop glycan affects to similar extents immune
      recognition by a panel of anti-HIV human and anti-simian/human immunodeficiency
      virus (anti-SHIV) macaque sera. All sera tested neutralized the glycan-deficient
      viruses, in which the conserved CD4BS and CD4i epitopes are more exposed, better
      than the glycan-containing viruses. The titer of broadly neutralizing antibodies
      appears to be higher in the sera of macaques infected with glycan-deficient
      viruses. Collectively, our data add legitimacy to the use of SHIV-macaque models
      for testing the efficacy of HIV-1 Env-based immunogens. Furthermore, they suggest
      that antibodies to the CD4BS and CD4i sites of gp120 are prevalent in human and
      macaque sera and that the use of immunogens in which these conserved neutralizing
      epitopes are more exposed is likely to increase their immunogenicity.

PMID- 11533192
TI  - Plasminogen-binding activity of neuraminidase determines the pathogenicity of
      influenza A virus.
AB  - When expressed in vitro, the neuraminidase (NA) of A/WSN/33 (WSN) virus binds and
      sequesters plasminogen on the cell surface, leading to enhanced cleavage of the
      viral hemagglutinin. To obtain direct evidence that the plasminogen-binding
      activity of the NA enhances the pathogenicity of WSN virus, we generated mutant
      viruses whose NAs lacked plasminogen-binding activity because of a mutation at
      the C terminus, from Lys to Arg or Leu. In the presence of trypsin, these mutant
      viruses replicated similarly to wild-type virus in cell culture. By contrast, in
      the presence of plasminogen, the mutant viruses failed to undergo multiple cycles
      of replication while the wild-type virus grew normally. The mutant viruses showed
      attenuated growth in mice and failed to grow at all in the brain. Furthermore,
      another mutant WSN virus, possessing an NA with a glycosylation site at position
      130 (146 in N2 numbering), leading to the loss of neurovirulence, failed to grow
      in cell culture in the presence of plasminogen. We conclude that the plasminogen
      binding activity of the WSN NA determines its pathogenicity in mice.

PMID- 11533193
TI  - Displacement of YY1 by differentiation-specific transcription factor hSkn-1a
      activates the P(670) promoter of human papillomavirus type 16.
AB  - Transcription from human papillomavirus type 16 (HPV16) P(670), a promoter in the
      E7 open reading frame, is repressed in undifferentiated keratinocytes but becomes
      activated upon differentiation. We showed that the transient luciferase
      expression driven by P(670) was markedly enhanced in HeLa cells cotransfected
      with an expression plasmid for human Skn-1a (hSkn-1a), a transcription factor
      specific to differentiating keratinocytes. The hSkn-1a POU domain alone, which
      mediates sequence-specific DNA binding, was sufficient to activate the expression
      of luciferase. Electrophoretic mobility shift assay revealed the presence of two
      binding sites, sites 1 and 2, upstream of P(670), which were shared by hSkn-1a
      and YY1. Site 1 bound more strongly to hSkn-1a than site 2 did. YY1 complexing
      with a short DNA fragment having site 1 was displaced by hSkn-1a, indicating that
      hSkn-1a's affinity with site 1 was stronger than YY1's. Disrupting the binding
      sites by nucleotide substitutions raised the basal expression level of luciferase
      and decreased the enhancing effect of hSkn-1a. In HeLa cells transfected with
      circular HPV16 DNA along with the expression plasmid for hSkn-1a, the transcript
      from P(670) was detectable, which indicates that the results obtained with the
      reporter plasmids are likely to have mimicked the regulation of P(670) in
      authentic HPV16 DNA. The data strongly suggest that the transcription from P(670)
      is repressed primarily by YY1 binding to the two sites, and the displacement of
      YY1 by hSkn-1a releases P(670) from the repression.

PMID- 11533194
TI  - Viral evolution toward change in receptor usage: adaptation of a major group
      human rhinovirus to grow in ICAM-1-negative cells.
AB  - Major receptor group common cold virus HRV89 was adapted to grow in HEp-2 cells,
      which are permissive for minor group human rhinoviruses (HRVs) but which only
      marginally support growth of major-group viruses. After 32 blind passages in
      these cells, each alternating with boosts of the recovered virus in HeLa cells,
      HRV89 acquired the capacity to effectively replicate in HEp-2 cells, attaining
      virus titers comparable to those in HeLa cells although no cytopathic effect was
      observed. Several clones were isolated and shown to replicate in HeLa cells whose
      ICAM-1 was blocked with monoclonal antibody R6.5 and in COS-7 cells, which are
      devoid of ICAM-1. Blocking experiments with recombinant very-low-density
      lipoprotein receptor fragments and enzyme-linked immunosorbent assays indicated
      that the mutants bound a receptor different from that used by minor-group
      viruses. Determination of the genomic RNA sequence encoding the capsid protein
      region revealed no changes in amino acid residues at positions equivalent to
      those involved in the interaction of HRV14 or HRV16 with ICAM-1. One mutation was
      within the footprint of a very-low-density lipoprotein receptor fragment bound to
      minor-group virus HRV2. Since ICAM-1 not only functions as a vehicle for cell
      entry but has also a "catalytic" function in uncoating, the use of other
      receptors must have important consequences for the entry pathway and demonstrates
      the plasticity of these viruses.

PMID- 11533195
TI  - Early spread of scrapie from the gastrointestinal tract to the central nervous
      system involves autonomic fibers of the splanchnic and vagus nerves.
AB  - Although the ultimate target of infection is the central nervous system (CNS),
      there is evidence that the enteric nervous system (ENS) and the peripheral
      nervous system (PNS) are involved in the pathogenesis of orally communicated
      transmissible spongiform encephalopathies. In several peripherally challenged
      rodent models of scrapie, spread of infectious agent to the brain and spinal cord
      shows a pattern consistent with propagation along nerves supplying the viscera.
      We used immunocytochemistry (ICC) and paraffin-embedded tissue (PET) blotting to
      identify the location and temporal sequence of pathological accumulation of a
      host protein, PrP, in the CNS, PNS, and ENS of hamsters orally infected with the
      263K scrapie strain. Enteric ganglia and components of splanchnic and vagus nerve
      circuitry were examined along with the brain and spinal cord. Bioassays were
      carried out with selected PNS constituents. Deposition of pathological PrP
      detected by ICC was consistent with immunostaining of a partially protease
      resistant form of PrP (PrP(Sc)) in PET blots. PrP(Sc) could be observed from
      approximately one-third of the way through the incubation period in enteric
      ganglia and autonomic ganglia of splanchnic or vagus circuitry prior to sensory
      ganglia. PrP(Sc) accumulated, in a defined temporal sequence, in sites that
      accurately reflected known autonomic and sensory relays. Scrapie agent
      infectivity was present in the PNS at low or moderate levels. The data suggest
      that, in this scrapie model, the infectious agent primarily uses synaptically
      linked autonomic ganglia and efferent fibers of the vagus and splanchnic nerves
      to invade initial target sites in the brain and spinal cord.

PMID- 11533196
TI  - Characteristics of a pathogenic molecular clone of an end-stage serum-derived
      variant of simian immunodeficiency virus (SIV(F359)).
AB  - End-stage simian immunodeficiency virus (SIV) isolates are suggested to be the
      most fit of the evolved virulent variants that precipitate the progression to
      AIDS. To determine if there were common characteristics of end-stage variants
      which emerge from accelerated cases of AIDS, a molecular clone was derived
      directly from serum following in vivo selection of a highly virulent SIV isolate
      obtained by serial end-stage passage in rhesus monkeys (Macaca mulatta). This
      dominant variant caused a marked cytopathic effect and replicated to very high
      levels in activated but not resting peripheral blood lymphocytes. Furthermore,
      although this clone infected but did not replicate to detectable levels in rhesus
      monocyte-derived macrophages, these cells were able to transmit infection to
      autologous T cells upon contact. Interestingly, although at low doses this end
      stage variant did not use any of the known coreceptors except CCR5, it was able
      to infect and replicate in human peripheral blood mononuclear cells homozygous
      for the Delta 32 deletion of CCR5, suggesting the use of a novel coreceptor. It
      represents the first pathogenic molecular clone of SIV derived from viral RNA in
      serum and provides evidence that not only the genetic but also the biological
      characteristics acquired by highly fit late-stage disease variants may be
      distinct in different hosts.

PMID- 11533197
TI  - Development of an avian leukosis-sarcoma virus subgroup A pseudotyped lentiviral
      vector.
AB  - We are using avian leukosis-sarcoma virus (ALSV) vectors to generate mouse tumor
      models in transgenic mice expressing TVA, the receptor for subgroup A ALSV. Like
      other classical retroviruses, ALSV requires cell division to establish a provirus
      after infection of host cells. In contrast, lentiviral vectors are capable of
      integrating their viral DNA into the genomes of nondividing cells. With the
      intention of initiating tumorigenesis in resting, TVA-positive cells, we have
      developed a system for the preparation of a human immunodeficiency virus type 1
      (HIV-1)-based lentiviral vector, pseudotyped with the envelope protein of ALSV
      subgroup A (EnvA). The HIV(ALSV-A) vector retains the requirement for TVA on the
      surface of target cells and can be produced at titers of 5 x 10(3) infectious
      units (IU)/ml. By inserting the central polypurine tract (cPPT) from the HIV-1
      pol gene and removing the cytoplasmic tail of EnvA, the pseudotype can be
      produced at titers approaching 10(5) IU/ml and can be concentrated by
      ultracentrifugation to titers of 10(7) IU/ml. HIV(ALSV-A) also infects embryonic
      fibroblasts derived from transgenic mice in which TVA expression is driven by the
      beta-actin promoter. In addition, this lentivirus pseudotype efficiently infects
      these fibroblasts after cell cycle arrest, when they are resistant to infection
      by ALSV vectors. This system may be useful for introducing genes into somatic
      cells in adult TVA transgenic animals and allows evaluation of the effects of
      altered gene expression in differentiated cell types in vivo.

PMID- 11533198
TI  - Localization to the nucleolus is a common feature of coronavirus nucleoproteins,
      and the protein may disrupt host cell division.
AB  - The subcellular localization of transmissible gastroenteritis virus (TGEV) and
      mouse hepatitis virus (MHV) (group I and group II coronaviruses, respectively)
      nucleoproteins (N proteins) were examined by confocal microscopy. The proteins
      were shown to localize either to the cytoplasm alone or to the cytoplasm and a
      structure in the nucleus. This feature was confirmed to be the nucleolus by using
      specific antibodies to nucleolin, a major component of the nucleolus, and by
      confocal microscopy to image sections through a cell expressing N protein. These
      findings are consistent with our previous report for infectious bronchitis virus
      (group III coronavirus) (J. A. Hiscox et al., J. Virol. 75:506-512, 2001),
      indicating that nucleolar localization of the N protein is a common feature of
      the coronavirus family and is possibly of functional significance. Nucleolar
      localization signals were identified in the domain III region of the N protein
      from all three coronavirus groups, and this suggested that transport of N protein
      to the nucleus might be an active process. In addition, our results suggest that
      the N protein might function to disrupt cell division. Thus, we observed that
      approximately 30% of cells transfected with the N protein appeared to be
      undergoing cell division. The most likely explanation for this is that the N
      protein induced a cell cycle delay or arrest, most likely in the G(2)/M phase. In
      a fraction of transfected cells expressing coronavirus N proteins, we observed
      multinucleate cells and dividing cells with nucleoli (which are only present
      during interphase). These findings are consistent with the possible inhibition of
      cytokinesis in these cells.

PMID- 11533199
TI  - Human immunodeficiency virus type 1 N-terminal capsid mutants that exhibit
      aberrant core morphology and are blocked in initiation of reverse transcription
      in infected cells.
AB  - A group of conserved hydrophobic residues faces the interior of the coiled-coil
      like structure within the N-terminal domain of the human immunodeficiency virus
      type 1 (HIV-1) capsid protein (CA). It has been suggested that these residues are
      important for maintaining stable structure and functional activity. To
      investigate this possibility, we constructed two HIV-1 clones, in which Trp23 or
      Phe40 was changed to Ala. We also constructed a third mutant, D51A, which has a
      mutation that destroys a salt bridge between Pro1 and Asp51. All three mutants
      are replication defective but produce virus particles. Mutant virions contain all
      of the viral proteins, although the amount and stability of CA are decreased and
      levels of virion-associated integrase are reduced. The mutations do not affect
      endogenous reverse transcriptase activity; however, the mutants are blocked in
      their ability to initiate reverse transcription in infected cells and no minus
      strand strong-stop DNA is detected. The defect in reverse transcription is
      associated with striking defects in the morphology of mutant virus cores, as
      determined by transmission electron microscopy. Our data indicate that the
      mutations made in this study disrupt CA structure and prevent proper maturation
      of virus cores. We propose that this results in a defect in core stability or in
      an early postentry event preceding reverse transcription.

PMID- 11533200
TI  - Chimeric bovine respiratory syncytial virus with attachment and fusion
      glycoproteins replaced by bovine parainfluenza virus type 3 hemagglutinin
      neuraminidase and fusion proteins.
AB  - Chimeric bovine respiratory syncytial viruses (BRSV) expressing glycoproteins of
      bovine parainfluenza virus type 3 (BPIV-3) instead of BRSV glycoproteins were
      generated from cDNA. In the BRSV antigenome cDNA, the open reading frames of the
      major BRSV glycoproteins, attachment protein G and fusion protein F, were
      replaced individually or together by those of the BPIV-3 hemagglutinin
      neuraminidase (HN) and/or fusion (F) glycoproteins. Recombinant virus could not
      be recovered from cDNA when the BRSV F open reading frame was replaced by the
      BPIV-3 F open reading frame. However, cDNA recovery of the chimeric virus rBRSV
      HNF, with both glycoproteins replaced simultaneously, and of the chimeric virus
      rBRSV-HN, with the BRSV G protein replaced by BPIV-3 HN, was successful. The
      replication rates of both chimeras were similar to that of standard rBRSV.
      Moreover, rBRSV-HNF was neutralized by antibodies specific for BPIV-3, but not by
      antibodies specific to BRSV, demonstrating that the BRSV glycoproteins can be
      functionally replaced by BPIV-3 glycoproteins. In contrast, rBRSV-HN was
      neutralized by BRSV-specific antisera, but not by BPIV-3 specific sera, showing
      that infection of rBRSV-HN is mediated by BRSV F. Hemadsorption of cells infected
      with rBRSV-HNF and rBRSV-HN proved that BPIV-3 HN protein expressed by rBRSV is
      functional. Colocalization of the BPIV-3 glycoproteins with BRSV M protein was
      demonstrated by confocal laser scan microscopy. Moreover, protein analysis
      revealed that the BPIV-3 glycoproteins were present in chimeric virions. Taken
      together, these data indicate that the heterologous glycoproteins were not only
      expressed but were incorporated into the envelope of recombinant BRSV. Thus, the
      envelope glycoproteins derived from a member of the Respirovirus genus can
      together functionally replace their homologs in a Pneumovirus background.

PMID- 11533201
TI  - The pathogenicity of human immunodeficiency virus (HIV) type 1 Nef in CD4C/HIV
      transgenic mice is abolished by mutation of its SH3-binding domain, and disease
      development is delayed in the absence of Hck.
AB  - The human immunodeficiency virus type 1 (HIV-1) Nef protein is an important
      determinant of AIDS pathogenesis. We have previously reported that HIV-1 Nef is
      responsible for the induction of a severe AIDS-like disease in CD4C/HIV
      transgenic (Tg) mice. To understand the molecular mechanisms of this Nef-induced
      disease, we generated Tg mice expressing a mutated Nef protein in which the SH3
      ligand-binding domain (P(72)XXP(75)XXP(78)) was mutated to A(72)XXA(75)XXQ(78).
      This mutation completely abolished the pathogenic potential of Nef, although a
      partial downregulation of the CD4 cell surface expression was still observed in
      these Tg mice. We also studied whether Hck, one of the effectors previously found
      to bind to this PXXP motif of Nef, was involved in disease development. Breeding
      of Tg mice expressing wild-type Nef on an hck(-/-) (knockout) background did not
      abolish any of the pathological phenotypes. However, the latency of disease
      development was prolonged. These data indicate that an intact PXXP domain is
      essential for inducing an AIDS-like disease in CD4C/HIV Tg mice and suggest that
      interaction of a cellular effector(s) with this domain is required for the
      induction of this multiorgan disease. Our findings indicate that Hck is an
      important, but not an essential, effector of Nef and suggest that another
      factor(s), yet to be identified, may be more critical for disease development.

PMID- 11533202
TI  - Interactions and nuclear import of the N and P proteins of sonchus yellow net
      virus, a plant nucleorhabdovirus.
AB  - We have characterized the interaction and nuclear localization of the
      nucleocapsid (N) protein and phosphoprotein (P) of sonchus yellow net
      nucleorhabdovirus. Expression studies with plant and yeast cells revealed that
      both N and P are capable of independent nuclear import. Site-specific mutagenesis
      and deletion analyses demonstrated that N contains a carboxy-terminal bipartite
      nuclear localization signal (NLS) located between amino acids 465 and 481 and
      that P contains a karyophillic region between amino acids 40 and 124. The N NLS
      was fully capable of functioning outside of the context of the N protein and was
      able to direct the nuclear import of a synthetic protein fusion consisting of
      green fluorescent protein fused to glutathione S-transferase (GST). Expression
      and mapping studies suggested that the karyophillic domain in P is located within
      the N-binding domain. Coexpression of N and P drastically affected their
      localization patterns relative to those of individually expressed proteins and
      resulted in a shift of both proteins to a subnuclear region. Yeast two-hybrid and
      GST pulldown experiments verified the N-P and P-P interactions, and deletion
      analyses have identified the N and P interacting domains. N NLS mutants were not
      transported to the nucleus by import-competent P, presumably because N binding
      masks the P NLS. Taken together, our results support a model for independent
      entry of N and P into the nucleus followed by associations that mediate
      subnuclear localization.

PMID- 11533203
TI  - Identification of a central DNA flap in feline immunodeficiency virus.
AB  - A duplication of the polypurine tract (PPT) at the center of the human
      immunodeficiency virus type 1 (HIV-1) genome (the cPPT) has been shown to prime a
      separate plus-strand initiation and to result in a plus-strand displacement (DNA
      flap) that plays a role in nuclear import of the viral preintegration complex.
      Feline immunodeficiency virus (FIV) is a lentivirus that infects nondividing
      cells, causes progressive CD4(+) T-cell depletion, and has been used as a
      substrate for lentiviral vectors. However, the PPT sequence is not duplicated
      elsewhere in the FIV genome and a central plus-strand initiation or strand
      displacement has not been identified. Using Southern blotting of S1 nuclease
      digested FIV preintegration complexes isolated from infected cells, we detected a
      single-strand discontinuity at the approximate center of the reverse-transcribed
      genome. Primer extension analyses assigned the gap to the plus strand, and mapped
      the 5' terminus of the downstream (D+) segment to a guanine residue in a purine
      rich tract in pol (AAAAGAAGAGGTAGGA). RACE experiments then mapped the 3'
      terminus of the upstream plus (U+)-strand segment to a T nucleotide located 88
      nucleotides downstream of the D+ strand 5' terminus, thereby identifying the
      extent of D+ strand displacement and the central termination sequence of this
      virus. Unlike HIV, the FIV cPPT is significantly divergent in sequence from its
      3' counterpart (AAAAAAGAAAAAAGGGTGG) and contains one and in some cases two
      pyrimidines. An invariant thymidine located -2 to the D+ strand origin is neither
      required nor optimal for codon usage at this position. Although the mapped cPPTs
      of FIV and HIV-1 act in cis, they encode homologous amino acids in integrase.

PMID- 11533204
TI  - RING finger Z protein of lymphocytic choriomeningitis virus (LCMV) inhibits
      transcription and RNA replication of an LCMV S-segment minigenome.
AB  - Arenaviruses have a bisegmented negative-strand RNA genome whose proteomic
      capability is limited to only four polypeptides, namely, nucleoprotein (NP),
      surface glycoprotein (GP) that is proteolytically processed into GP1+GP2,
      polymerase (L), and a small (11-kDa) RING finger protein (Z). The role of Z
      during the Lymphocytic choriomeningitis virus (LCMV) life cycle is poorly
      understood. We investigated the function of Z in virus transcription and
      replication by using a reverse genetic system for the prototypic arenavirus LCMV.
      This system involves an LCMV minigenome and the minimal viral trans-acting
      factors (NP and L), expressed from separated cotransfected plasmids.
      Cotransfection of the Z cDNA strongly inhibited LCMV minigenome expression. The
      effect required synthesis of Z protein; its magnitude was dose dependent and
      occurred with levels of Z protein substantially lower than those observed in LCMV
      infected cells. Coexpression of Z did not prevent the encapsidation of plasmid
      supplied minigenome, but it affected both transcription and RNA replication
      similarly. Mutations in Z that unfolded its RING finger domain eliminated its
      inhibitory activity, but RING proteins not related to Z did not affect LCMV
      minigenome expression. Consistent with the minigenome results, cells transiently
      expressing Z exhibited decreased susceptibility to infection with LCMV.

PMID- 11533205
TI  - Retroviral integration at the Epi1 locus cooperates with Nf1 gene loss in the
      progression to acute myeloid leukemia.
AB  - Juvenile myelomonocytic leukemia (JMML) is a disease that occurs in young
      children and is associated with a high mortality rate. In most patients, JMML has
      a progressive course leading to death by virtue of infection, bleeding, or
      progression to acute myeloid leukemia (AML). As it is known that children with
      neurofibromatosis type 1 syndrome have a markedly increased risk of developing
      JMML, we have previously developed a mouse model of JMML through reconstitution
      of lethally irradiated mice with hematopoietic stem cells homozygous for a loss
      of-function mutation in the Nf1 gene (D. L. Largaespada, C. I. Brannan, N. A.
      Jenkins, and N. G. Copeland, Nat. Genet. 12:137-143, 1996). In the course of
      these experiments, we found that all these genetically identical reconstituted
      mice developed a JMML-like disorder, but only a subset went on to develop more
      acute disease. This result strongly suggests that additional genetic lesions are
      responsible for disease progression to AML. Here, we describe the production of a
      unique tumor panel, created using the BXH-2 genetic background, for
      identification of these additional genetic lesions. Using this tumor panel, we
      have identified a locus, Epi1, which maps 30 to 40 kb downstream of the Myb gene
      and appears to be the most common site of somatic viral integration in BXH-2
      mice. Our findings suggest that proviral integrations at Epi1 cooperate with loss
      of Nf1 to cause AML.

PMID- 11533206
TI  - Cross-linking of the fingers subdomain of human immunodeficiency virus type 1
      reverse transcriptase to template-primer.
AB  - Cross-linking experiments were performed with human immunodeficiency virus type 1
      (HIV-1) reverse transcriptase (RT) mutants with unique cysteine residues at
      several positions (positions 65, 67, 70, and 74) in the fingers subdomain of the
      p66 subunit. Two approaches were used--photoaffinity cross-linking and disulfide
      chemical cross-linking (using an oligonucleotide that contained an N(2)-modified
      dG with a reactive thiol group). In the former case, cross-linking can occur to
      any nucleotide in either DNA strand, and in the latter case, a specific cross
      link is produced between the template and the enzyme. Neither the introduction of
      the unique cysteine residues into the fingers nor the modification of these
      residues with photocross-linking reagents caused a significant decrease in the
      enzymatic activities of RT. We were able to use this model system to investigate
      interactions between specific points on the fingers domain of RT and double
      stranded DNA (dsDNA). Photoaffinity cross-linking of the template to the modified
      RTs with Cys residues in positions 65, 67, 70, and 74 of the fingers domain of
      the p66 subunit was relatively efficient. Azide-modified Cys residues produced 10
      to 25% cross-linking, whereas diazirine modified residues produced 5 to 8% cross
      linking. Disulfide cross-linking yields were up to 90%. All of the modified RTs
      preferentially photocross-linked to the 5' extended template strand of the dsDNA
      template-primer substrate. The preferred sites of interactions were on the
      extended template, 5 to 7 bases beyond the polymerase active site. HIV-1 RT is
      quite flexible. There are conformational changes associated with substrate
      binding. Cross-linking was used to detect intramolecular movements associated
      with binding of the incoming deoxynucleoside triphosphate (dNTP). Binding an
      incoming dNTP at the polymerase active site decreases the efficiency of cross
      linking, but causes only modest changes in the preferred positions of cross
      linking. This suggests that the interactions between the fingers of p66 and the
      extended template involve the "open" configuration of the enzyme with the fingers
      away from the active site rather than the closed configuration with the fingers
      in direct contact with the incoming dNTP. This experimental approach can be used
      to measure distances between any site on the surface of the protein and an
      interacting molecule.

PMID- 11533207
TI  - The latency-associated nuclear antigen encoded by Kaposi's sarcoma-associated
      herpesvirus activates two major essential Epstein-Barr virus latent promoters.
AB  - The latency-associated nuclear antigen (LANA) encoded by the Kaposi's sarcoma
      associated herpesvirus (KSHV) is expressed in the majority of KSHV-infected cells
      and in cells coinfected with Epstein-Barr virus (EBV). In coinfected body cavity
      based lymphomas (BCBLs), EBV latent membrane protein 1 (LMP1), which is essential
      for B-lymphocyte transformation, is expressed. EBNA2 upregulates the expression
      of LMP1 and other cellular genes through specific interactions with cellular
      transcription factors tethering EBNA2 to its responsive promoters. In coinfected
      BCBL cells, EBNA2 is not detected but LANA, which is constitutively expressed,
      contains motifs suggestive of potential transcriptional activity. Additionally,
      recent studies have shown that LANA is capable of activating cellular promoters.
      Therefore, we investigated whether LANA can affect transcription from two major
      EBV latent promoters. In this study, we demonstrated that LANA can efficiently
      transactivate both the LMP1 and C promoters in the human B-cell line BJAB as well
      as in the human embryonic kidney 293 cell line. Moreover, we demonstrated that
      specific domains of LANA containing the putative leucine zipper and the glutamic
      acid-rich region are highly effective in upregulating these viral promoters,
      while the amino-terminal region (435 amino acids) exhibited little or no
      transactivation activity in our assays. We also specifically tested truncations
      of the LMP1 promoter element and showed that the -204 to +40 region had increased
      levels of activation compared with a larger region, -512 to +40, which contains
      two recombination signal-binding protein J kappa binding sites. The smaller, -204
      to +40 promoter region contains specific binding sites for the Ets family
      transcription factor PU.1, transcription activating factor/cyclic AMP response
      element, and Sp1, all of which are known to function as activators of
      transcription. Our data therefore suggest a potential role for LANA in regulation
      of the major EBV latent promoters in KSHV- and EBV-coinfected cells. Furthermore,
      LANA may be able to activate transcription of viral and cellular promoters in the
      absence of EBNA2, potentially through association with transcription factors
      bound to their cognate sequences within the -204 to +40 region. This regulation
      of viral gene expression is critical for persistence of these DNA tumor viruses
      and most likely involved in mediating the oncogenic process in these coinfected
      cells.

PMID- 11533208
TI  - Molecular basis for the relative substrate specificity of human immunodeficiency
      virus type 1 and feline immunodeficiency virus proteases.
AB  - We have used a random hexamer phage library to delineate similarities and
      differences between the substrate specificities of human immunodeficiency virus
      type 1 (HIV-1) and feline immunodeficiency virus (FIV) proteases (PRs). Peptide
      sequences were identified that were specifically cleaved by each protease, as
      well as sequences cleaved equally well by both enzymes. Based on amino acid
      distinctions within the P3-P3' region of substrates that appeared to correlate
      with these cleavage specificities, we prepared a series of synthetic peptides
      within the framework of a peptide sequence cleaved with essentially the same
      efficiency by both HIV-1 and FIV PRs, Ac-KSGVF/VVNGLVK-NH(2) (arrow denotes
      cleavage site). We used the resultant peptide set to assess the influence of
      specific amino acid substitutions on the cleavage characteristics of the two
      proteases. The findings show that when Asn is substituted for Val at the P2
      position, HIV-1 PR cleaves the substrate at a much greater rate than does FIV PR.
      Likewise, Glu or Gln substituted for Val at the P2' position also yields peptides
      specifically susceptible to HIV-1 PR. In contrast, when Ser is substituted for
      Val at P1', FIV PR cleaves the substrate at a much higher rate than does HIV-1
      PR. In addition, Asn or Gln at the P1 position, in combination with an
      appropriate P3 amino acid, Arg, also strongly favors cleavage by FIV PR over HIV
      PR. Structural analysis identified several protease residues likely to dictate
      the observed specificity differences. Interestingly, HIV PR Asp30 (Ile-35 in FIV
      PR), which influences specificity at the S2 and S2' subsites, and HIV-1 PR Pro-81
      and Val-82 (Ile-98 and Gln-99 in FIV PR), which influence specificity at the S1
      and S1' subsites, are residues which are often involved in development of drug
      resistance in HIV-1 protease. The peptide substrate KSGVF/VVNGK, cleaved by both
      PRs, was used as a template for the design of a reduced amide inhibitor, Ac-GSGVF
      Psi(CH(2)NH)VVNGL-NH(2.) This compound inhibited both FIV and HIV-1 PRs with
      approximately equal efficiency. These findings establish a molecular basis for
      distinctions in substrate specificity between human and feline lentivirus PRs and
      offer a framework for development of efficient broad-based inhibitors.

PMID- 11533209
TI  - A cellular J-domain protein modulates polyprotein processing and
      cytopathogenicity of a pestivirus.
AB  - Pestiviruses are positive-strand RNA viruses closely related to human hepatitis C
      virus. Gene expression of these viruses occurs via translation of a polyprotein,
      which is further processed by cellular and viral proteases. Here we report the
      formation of a stable complex between an as-yet-undescribed cellular J-domain
      protein, a member of the DnaJ-chaperone family, and pestiviral nonstructural
      protein NS2. Accordingly, we termed the cellular protein Jiv, for J-domain
      protein interacting with viral protein. Jiv has the potential to induce in trans
      one specific processing step in the viral polyprotein, namely, cleavage of NS2-3.
      Efficient generation of its cleavage product NS3 has previously been shown to be
      obligatory for the cytopathogenicity of the pestiviruses. Regulated expression of
      Jiv in cells infected with noncytopathogenic bovine viral diarrhea virus
      disclosed a direct correlation between the intracellular level of Jiv, the extent
      of NS2-3 cleavage, and pestiviral cytopathogenicity.

PMID- 11533210
TI  - Varicella-zoster Virus gB and gE coexpression, but not gB or gE alone, leads to
      abundant fusion and syncytium formation equivalent to those from gH and gL
      coexpression.
AB  - Varicella-zoster virus (VZV) is distinguished from herpes simplex virus type 1
      (HSV-1) by the fact that cell-to-cell fusion and syncytium formation require only
      gH and gL within a transient-expression system. In the HSV system, four
      glycoproteins, namely, gH, gL, gB, and gD, are required to induce a similar
      fusogenic event. VZV lacks a gD homologous protein. In this report, the role of
      VZV gB as a fusogen was investigated and compared to the gH-gL complex. First of
      all, the VZV gH-gL experiment was repeated under a different set of conditions;
      namely, gH and gL were cloned into the same vaccinia virus (VV) genome.
      Surprisingly, the new expression system demonstrated that a recombinant VV-gH+gL
      construct was even more fusogenic than seen in the prior experiment with two
      individual expression plasmids containing gH and gL (K. M. Duus and C. Grose, J.
      Virol. 70:8961-8971, 1996). Recombinant VV expressing VZV gB by itself, however,
      effected the formation of only small syncytia. When VZV gE and gB genes were
      cloned into one recombinant VV genome and another fusion assay was performed,
      extensive syncytium formation was observed. The degree of fusion with VZV gE-gB
      coexpression was comparable to that observed with VZV gH-gL: in both cases, >80%
      of the cells in a monolayer were fused. Thus, these studies established that VZV
      gE-gB coexpression greatly enhanced the fusogenic properties of gB. Control
      experiments documented that the fusion assay required a balance between the
      fusogenic potential of the VZV glycoproteins and the fusion-inhibitory effect of
      the VV infection itself.

PMID- 11533211
TI  - Adeno-associated virus type 2-mediated transduction of human monocyte-derived
      dendritic cells: implications for ex vivo immunotherapy.
AB  - Dendritic cells (DCs) are pivotal antigen-presenting cells for regulating immune
      responses. A major focus of contemporary vaccine research is the genetic
      modification of DCs to express antigens or immunomodulatory molecules, utilizing
      a variety of viral and nonviral vectors, to induce antigen-specific immune
      responses that ameliorate disease states as diverse as malignancy, infection,
      autoimmunity, and allergy. The present study has evaluated adeno-associated virus
      (AAV) type 2 as a vector for ex vivo gene transfer to human peripheral blood
      monocyte (MO)-derived DCs. AAV is a nonpathogenic parvovirus that infects a wide
      variety of human cell lineages in vivo and in vitro, for long-term transgene
      expression without requirements for cell proliferation. The presented data
      demonstrate that recombinant AAV (rAAV) can efficiently transduce MOs as well as
      DCs generated by MO culture with granulocyte-macrophage colony-stimulating factor
      plus interleukin in vitro. rAAV transgene expression in MO-derived DCs could be
      enhanced by etoposide, previously reported to enhance AAV gene expression. rAAV
      transduction of freshly purified MO followed by 7 days of culture with cytokines
      to generate DCs, and subsequent sorting for coexpression of DC markers CD1a and
      CD40, showed robust transgene expression as well as evidence of nuclear
      localization of the rAAV genome in the DC population. Phenotypic analyses using
      multiple markers and functional assays of one-way allogeneic mixed leukocyte
      reactions indicated that rAAV-transduced MO-derived DCs were as equivalent to
      nontransduced DCs. These results support the utility of rAAV vectors for future
      human DC vaccine studies.

PMID- 11533212
TI  - Viral evolution in response to the broad-based retroviral protease inhibitor TL
      3.
AB  - TL-3 is a protease inhibitor developed using the feline immunodeficiency virus
      protease as a model. It has been shown to efficiently inhibit replication of
      human, simian, and feline immunodeficiency viruses and therefore has broad-based
      activity. We now demonstrate that TL-3 efficiently inhibits the replication of 6
      of 12 isolates with confirmed resistance mutations to known protease inhibitors.
      To dissect the spectrum of molecular changes in protease and viral properties
      associated with resistance to TL-3, a panel of chronological in vitro escape
      variants was generated. We have virologically and biochemically characterized
      mutants with one (V82A), three (M46I/F53L/V82A), or six
      (L24I/M46I/F53L/L63P/V77I/V82A) changes in the protease and structurally modeled
      the protease mutant containing six changes. Virus containing six changes was
      found to be 17-fold more resistant to TL-3 in cell culture than was wild-type
      virus but maintained similar in vitro replication kinetics compared to the wild
      type virus. Analyses of enzyme activity of protease variants with one, three, and
      six changes indicated that these enzymes, compared to wild-type protease,
      retained 40, 47, and 61% activity, respectively. These results suggest that
      deficient protease enzymatic activity is sufficient for function, and the
      observed protease restoration might imply a selective advantage, at least in
      vitro, for increased protease activity.

PMID- 11533213
TI  - The Kaposi's sarcoma-associated herpesvirus K8 protein interacts with CREB
      binding protein (CBP) and represses CBP-mediated transcription.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV) open reading frame K8 encodes a
      basic region-leucine zipper protein of 237 amino acids that homodimerizes with
      its bZIP domain. KSHV K8 shows significant homology to the Epstein-Barr virus
      (EBV) immediate-early protein Zta, a key regulator in the reactivation and
      replication of EBV. In this study, we report that K8, like its homolog EBV Zta,
      interacts with cellular CREB-binding protein (CBP) in vivo and in vitro. This
      interaction requires the C/H3 domain of CBP and the basic region of K8. K8
      represses CBP-mediated transcription by competing with limited amounts of
      cellular CBP, exemplified by the reduced expression from the AP-1 and human
      immunodeficiency virus long terminal repeat promoters.

PMID- 11533214
TI  - Characterization of a porcine lung epithelial cell line suitable for influenza
      virus studies.
AB  - We established a porcine lung epithelial cell line designated St. Jude porcine
      lung cells (SJPL) and demonstrated that all tested influenza A and B viruses
      replicated in this cell line. The infectivity titers of most viruses in SJPL
      cells were comparable to or better than those in MDCK cells. The propagation of
      influenza viruses from clinical samples in SJPL cells did not lead to antigenic
      changes in the hemagglutinin molecule. The numbers of both Sia2-3Gal and Sia2
      6Gal receptors on SJPL cells were greater than those on MDCK cells. Influenza
      virus infection of SJPL cells did not lead to apoptosis, as did infection of MDCK
      cells. No porcine endogenous retrovirus was detected in SJPL cells, and in
      contrast to MDCK cells, SJPL cells did not cause tumors in nude mice.

PMID- 11533215
TI  - Infection of nondividing cells by Rous sarcoma virus.
AB  - A direct comparison demonstrates that Rous sarcoma virus is capable of infecting
      aphidicolin-arrested cells 10-fold more efficiently than murine leukemia virus
      but less efficiently than human immunodeficiency virus. The efficiency of
      infection of nondividing cells by the three viruses correlates with the
      respective ability of each viral DNA to enter the nucleus.

PMID- 11533216
TI  - Venezuelan equine encephalomyelitis virus structure and its divergence from old
      world alphaviruses.
AB  - Although alphaviruses have been extensively studied as model systems for the
      structural organization of enveloped viruses, no structures exist for the
      phylogenetically distinct eastern equine encephalomyelitis (EEE)-Venezuelan
      equine encephalomyelitis (VEE) lineage of New World alphaviruses. Here we report
      the 25-A structure of VEE virus, obtained from electron cryomicroscopy and image
      reconstruction. The envelope spike glycoproteins of VEE virus have a T=4
      icosahedral arrangement, similar to that observed in Old World Sindbis, Semliki
      Forest, and Ross River alphaviruses. However, VEE virus has pronounced
      differences in its nucleocapsid structure relative to nucleocapsid structures
      repeatedly observed in Old World alphaviruses.

PMID- 11533217
TI  - A single amino acid mutation in the carnation ringspot virus capsid protein
      allows virion formation but prevents systemic infection.
AB  - A Carnation ringspot virus (CRSV) variant (1.26) was identified that accumulates
      virions but is incapable of forming a systemic infection. The 1.26 capsid protein
      gene possesses a Ser-->Pro mutation at amino acid 282. Conversion of 1.26 amino
      acid 282 to Ser restored systemic infection, while the reciprocal mutation in
      wild-type CRSV abolished systemic infection. Similar mutations introduced into
      the related Red clover necrotic mosaic virus capsid protein gene failed to induce
      the packaging but nonsystemic movement phenotype. These results provide
      additional support for the theory that virion formation is necessary but not
      sufficient for systemic movement with the dianthoviruses.

PMID- 11533218
TI  - Analysis of Mason-Pfizer monkey virus Gag particles by scanning transmission
      electron microscopy.
AB  - Mason-Pfizer monkey virus immature capsids selected from the cytoplasm of
      baculovirus-infected cells were imaged by scanning transmission electron
      microscopy. The masses of individual selected Gag particles were measured, and
      the average mass corresponded to 1,900 to 2,100 Gag polyproteins per particle. A
      large variation in Gag particle mass was observed within each population
      measured.

PMID- 11533219
TI  - Characterization of retrovirus-host DNA junctions in cells deficient in
      nonhomologous-end joining.
AB  - Formation of stably integrated proviruses is inefficient in cells that are
      defective in the cellular nonhomologous end-joining (NHEJ) DNA repair pathway (R.
      Daniel, R. A. Katz, and A. M. Skalka, Science 284:644-647, 1999; R. Daniel, R. A.
      Katz, and A. M. Skalka, Mol. Cell. Biol. 21:1164-1172, 2001). However, the
      requirement for NHEJ function is not absolute, as 10 to 20% of infected NHEJ
      deficient cells can express retrovirus- transduced reporter genes in a stable
      fashion. To learn more about the compensatory mechanism by which viral DNA may be
      incorporated into the host cell genome, we analyzed the nucleotide sequences of
      provirus-host DNA junctions in singly infected NHEJ-deficient cell clones. The
      results showed that the proviral DNA ends in all NHEJ-deficient clones had the
      normal 5'TG...CA3' sequence. In addition, 14 of the 19 proviruses analyzed were
      flanked by a 6-bp direct repeat of host sequences, as is characteristic for avian
      sarcoma virus integration. These results indicate that the DNA repair pathway
      which compensates for loss of NHEJ in these transductants does not introduce any
      gross abnormalities at the provirus-host DNA junctions.

PMID- 11533220
TI  - Characterization of envelope glycoprotein mutants for human T-cell leukemia virus
      type 1 infectivity and immortalization.
AB  - The human T-cell leukemia virus type 1 (HTLV-1) envelope protein is required for
      virus spread. This study further characterizes the role of the envelope protein
      in HTLV-1 immortalization. Viruses with single amino acid substitutions within
      the SU protein at residue 75, 81, 95, 101, 105, or 195 or with a C-terminal
      cytoplasmic domain truncation (CT), as well as an envelope-null (EN) virus, were
      generated within an infectious molecular clone, ACH. Transfection of 293T cells
      resulted in the release of similar amounts of virus particles from all of the
      mutants as determined by p19 enzyme-linked immunosorbent assay and immunoblot
      analysis of Gag in cell lysates and supernatants. The virus particles from all
      mutants except ACH-101, ACH-CT, and ACH-EN were infectious for B5 macaque cells
      in cell-free and cell-to-cell transmission assays and were capable of
      immortalizing transfected CD4(+) lymphocytes. These results indicate that HTLV-1
      spread is required for immortalization.

PMID- 11533221
TI  - Evidence for processing stages in skill acquisition: a dual-task study.
AB  - We investigated the changes of resource demand during the acquisition of a
      sensorimotor skill, namely the tracking of a visual target under reversed visual
      feedback. This acquisition task was performed alone or concurrently with one of
      four manual reaction-time tasks as loading tasks, designed to tap different
      computational resources. As expected, we found tracking performance to
      deteriorate upon vision reversal and then to gradually improve with practice. We
      further found that acquisition task and loading task interfered little before
      vision reversal but substantially afterwards. Most importantly, we observed a
      different time-course of interference for each of our four loading tasks. The
      particular pattern led us to conclude that resources related to spatial attention
      and sensory transformations are in highest demand early during skill acquisition
      and those pertinent to movement preparation somewhat later. Our findings thus
      provide experimental support for the theory that motor learning progresses in
      stages characterized by different resource requirements.

PMID- 11533222
TI  - Simple and associative recognition memory in the hippocampal region.
AB  - Although it is well established that the hippocampal region is involved in the
      formation of declarative memory, the exact nature of its involvement is unclear.
      One view is that the hippocampal region is involved only in tasks that require
      the formation or use of associations. According to this view, the hippocampal
      region is not involved in traditional tests of recognition memory. An alternative
      view is that the hippocampal region combines and extends the processing carried
      out by structures in the parahippocampal gyrus and that it is involved in all
      forms of declarative memory, including recognition memory. Using event-related
      functional magnetic resonance imaging (fMRI), we observed hippocampal activity
      during both traditional and associative recognition memory tasks. Critically, the
      hippocampal region was no more active in the associative recognition task than in
      the traditional recognition task.

PMID- 11533223
TI  - Massed and spaced learning in honeybees: the role of CS, US, the intertrial
      interval, and the test interval.
AB  - Conditioning the proboscis extension reflex of harnessed honeybees (Apis
      mellifera) is used to study the effect temporal spacing between successive
      conditioning trials has on memory. Retention is monitored at two long-term
      intervals corresponding to early (1 and 2 d after conditioning) and late long
      term memory (3 and 4 d). The acquisition level is varied by using different
      conditioned stimuli (odors, mechanical stimulation, and temperature increase at
      the antenna), varying strengths of the unconditioned stimulus (sucrose), and
      various numbers of conditioning trials. How learning trials are spaced is the
      dominant factor both for acquisition and retention, and although longer
      intertrial intervals lead to better acquisition and higher retention, the level
      of acquisition per se does not determine the spacing effect on retention. Rather,
      spaced conditioning leads to higher memory consolidation both during acquisition
      and later, between the early and long-term memory phases. These consolidation
      processes can be selectively inhibited by blocking protein synthesis during
      acquisition.

PMID- 11533224
TI  - Identification of genes expressed in the amygdala during the formation of fear
      memory.
AB  - In this study we describe changes of gene expression that occur in the
      basolateral complex of the mouse amygdala (BLA) during the formation of fear
      memory. Through the combination of a behavioral training scheme with polymerase
      chain reaction-based expression analysis (subtractive hybridization and virtual
      Northern analysis) we were able to identify various gene products that are
      increased in expression after Pavlovian fear conditioning and are of potential
      significance for neural plasticity and information storage in the amygdala. In
      particular, a key enzyme of monoamine metabolism, aldehyde reductase, and the
      protein sorting and ubiquitination factor Praja1, showed pronounced and learning
      specific induction six hours after fear conditioning training. Aldehyde reductase
      and Praja1, including a novel alternatively spliced isoform termed Praja1a, were
      induced in the BLA depending on the emotional stimulus presented and showed
      different expression levels in response to associative conditioning, training
      stress, and experience of conditioned fear. Stress and fear were further found to
      induce various signal transduction factors (transthyretin, phosphodiesterase1,
      protein kinase inhibitor-alpha) and structural reorganization factors (e.g., E2
      ubiquitin conjugating enzyme, neuroligin1, actin, UDP-galactose transporter)
      during training. Our results show that the formation of Pavlovian fear memory is
      associated with changes of gene expression in the BLA, which may contribute to
      neural plasticity and the processing of information about both conditioned and
      unconditioned fear stimuli.

PMID- 11533225
TI  - Overexpression of and RNA interference with the CCAAT enhancer-binding protein on
      long-term facilitation of Aplysia sensory to motor synapses.
AB  - In the marine mollusk Aplysia, the CCAAT/enhancer-binding protein, ApC/EBP,
      serves as an immediate early gene in the consolidation of long-term facilitation
      in the synaptic connection between the sensory and motor neurons of the gill
      withdrawal reflex. To further examine the role of ApC/EBP as a molecular switch
      of a stable form of long-term memory, we cloned the full-length coding regions of
      two alternatively spliced forms, the short and long form of ApC/EBP.
      Overexpression of each isoform by DNA microinjection resulted in a l6-fold
      increase in the expression of the coinjected luciferase reporter gene driven by
      an ERE promoter. In addition, when we overexpressed ApC/EBP in Aplysia sensory
      neurons, we found that the application of a single pulse of 5-HT that normally
      induced only short-term facilitation now induced long-term facilitation.
      Conversely, when we attempted to block the synthesis of native ApC/EBP by
      microinjecting double-strand RNA or antisense RNA, we blocked long-term
      facilitation in a sequence-specific manner. These data support the idea that
      ApC/EBP is both necessary and sufficient to consolidate short-term memory into
      long-term memory. Furthermore, our results suggest that this double-strand RNA
      interference provides a powerful tool in the study of the genes functioning in
      learning and memory in Aplysia by specifically inhibiting both the constitutive
      and induced expression of the genes.

PMID- 11533226
TI  - Transcription-independent RNA polymerase II dephosphorylation by the FCP1 carboxy
      terminal domain phosphatase in Xenopus laevis early embryos.
AB  - The phosphorylation of the RNA polymerase II (RNAP II) carboxy-terminal domain
      (CTD) plays a key role in mRNA metabolism. The relative ratio of
      hyperphosphorylated RNAP II to hypophosphorylated RNAP II is determined by a
      dynamic equilibrium between CTD kinases and CTD phosphatase(s). The CTD is
      heavily phosphorylated in meiotic Xenopus laevis oocytes. In this report we show
      that the CTD undergoes fast and massive dephosphorylation upon fertilization. A
      cDNA was cloned and shown to code for a full-length xFCP1, the Xenopus orthologue
      of the FCP1 CTD phosphatases in humans and Saccharomyces cerevisiae. Two critical
      residues in the catalytic site were identified. CTD phosphatase activity was
      observed in extracts prepared from Xenopus eggs and cells and was shown to be
      entirely attributable to xFCP1. The CTD dephosphorylation triggered by
      fertilization was reproduced upon calcium activation of cytostatic factor
      arrested egg extracts. Using immunodepleted extracts, we showed that this
      dephosphorylation is due to xFCP1. Although transcription does not occur at this
      stage, phosphorylation appears as a highly dynamic process involving the
      antagonist action of Xp42 mitogen-activated protein kinase and FCP1 phosphatase.
      This is the first report that free RNAP II is a substrate for FCP1 in vivo,
      independent from a transcription cycle.

PMID- 11533227
TI  - Interferon regulatory factor 4 contributes to transformation of v-Rel-expressing
      fibroblasts.
AB  - The avian homologue of the interferon regulatory factor 4 (IRF-4) and a novel
      splice variant lacking exon 6, IRF-4DeltaE6, were isolated and characterized.
      Chicken IRF-4 is expressed in lymphoid organs, less in small intestine, and
      lungs. IRF-4DeltaE6 mRNA, though less abundant than full-length IRF-4, was
      detected in lymphoid tissues, with the highest levels observed in thymic cells.
      IRF-4 is highly expressed in v-Rel-transformed lymphocytes, and the expression of
      IRF-4 is increased in v-Rel- and c-Rel-transformed fibroblasts relative to
      control cells. The expression of IRF-4 from retrovirus vectors morphologically
      transformed primary fibroblasts, increased their saturation density,
      proliferation, and life span, and promoted their growth in soft agar. IRF-4 and v
      Rel cooperated synergistically to transform fibroblasts. The expression of IRF-4
      antisense RNA eliminated formation of soft agar colonies by v-Rel and reduced the
      proliferation of v-Rel-transformed cells. v-Rel-transformed fibroblasts produced
      interferon 1 (IFN1), which inhibits fibroblast proliferation. Infection of
      fibroblasts with retroviruses expressing v-Rel resulted in an increase in the
      mRNA levels of IFN1, the IFN receptor, STAT1, JAK1, and 2',5'-oligo(A)
      synthetase. The exogenous expression of IRF-4 in v-Rel-transformed fibroblasts
      decreased the production of IFN1 and suppressed the expression of several genes
      in the IFN transduction pathway. These results suggest that induction of IRF-4
      expression by v-Rel likely facilitates transformation of fibroblasts by
      decreasing the induction of this antiproliferative pathway.

PMID- 11533228
TI  - Receptor heterodimerization: essential mechanism for platelet-derived growth
      factor-induced epidermal growth factor receptor transactivation.
AB  - Previous studies showed that the epidermal growth factor receptor (EGFR) can be
      transactivated by platelet-derived growth factor (PDGF) stimulation and that EGFR
      transactivation is required for PDGF-stimulated cell migration. To investigate
      the mechanism for cross talk between the PDGF beta receptor (PDGFbetaR) and the
      EGFR, we stimulated rat aortic vascular smooth muscle cells (VSMC) with 20 ng of
      PDGF/ml. Transactivation of the EGFR, defined by receptor tyrosine
      phosphorylation, occurred with the same time course as PDGFbetaR activation.
      Basal formation of PDGFbetaR-EGFR heterodimers was shown by coimmunoprecipitation
      studies, and interestingly, disruption of this receptor heterodimer abolished
      EGFR transactivation. Breakdown of the heterodimer was observed when VSMC were
      pretreated with antioxidants or with a Src family kinase inhibitor. Disruption of
      heterodimers decreased ERK1 and ERK2 activation by PDGF. Although PDGF-induced
      PDGFbetaR activation was abolished after pretreatment with 1 microM AG1295 (a
      specific PDGF receptor kinase inhibitor), EGFR transactivation was still
      observed, indicating that PDGFbetaR kinase activity is not required. In
      conclusion, our data demonstrate that the PDGFbetaR and the EGFR form PDGFbetaR
      EGFR heterodimers basally, and we suggest that heterodimers represent a novel
      signaling complex which plays an important role in PDGF signal transduction.

PMID- 11533229
TI  - Upc2p and Ecm22p, dual regulators of sterol biosynthesis in Saccharomyces
      cerevisiae.
AB  - Sterol levels affect the expression of many genes in yeast and humans. We found
      that the paralogous transcription factors Upc2p and Ecm22p of yeast were sterol
      regulatory element (SRE) binding proteins (SREBPs) responsible for regulating
      transcription of the sterol biosynthetic genes ERG2 and ERG3. We defined a 7-bp
      SRE common to these and other genes, including many genes involved in sterol
      biosynthesis. Upc2p and Ecm22p activated ERG2 expression by binding directly to
      this element in the ERG2 promoter. Upc2p and Ecm22p may thereby coordinately
      regulate genes involved in sterol homeostasis in yeast. Ecm22p and Upc2p are
      members of the fungus-specific Zn[2]-Cys[6] binuclear cluster family of
      transcription factors and share no homology to the analogous proteins, SREBPs,
      that are responsible for transcriptional regulation by sterols in humans. These
      results suggest that Saccharomyces cerevisiae and human cells regulate sterol
      synthesis by different mechanisms.

PMID- 11533230
TI  - Domains in human splicing factors SF3a60 and SF3a66 required for binding to
      SF3a120, assembly of the 17S U2 snRNP, and prespliceosome formation.
AB  - The active 17S U2 small nuclear ribonucleoprotein particle (snRNP), which binds
      to the intron branch site during the formation of the prespliceosome, is
      assembled in vitro by sequential interactions of the essential splicing factors
      SF3b and SF3a with the 12S U2 snRNP. We have analyzed the function of individual
      subunits of human SF3a (SF3a60, SF3a66, and SF3a120) by testing recombinant
      proteins, expressed in insect cells, in various in vitro assays. The recombinant
      subunits readily form the SF3a heterotrimer, where SF3a60 and SF3a66 interact
      with SF3a120, but not with each other. All SF3a subunits are essential for the
      formation of the mature 17S U2 snRNP and the prespliceosome. Single subunits
      engage in interactions with the 15S U2 snRNP (consisting of the 12S U2 snRNP and
      SF3b), and SF3a60 appears to play a major role in recruiting SF3a120 into the U2
      particle. Analysis of functional domains in SF3a60 and SF3a66 identified
      interaction sites for SF3a120 in their N-terminal portions. C(2)H(2)-type zinc
      finger domains mediate the integration of SF3a60 and SF3a66 into the U2 snRNP,
      and we propose a model in which protein-protein interactions between the zinc
      finger domains and the Sm proteins, common to all spliceosomal snRNPs, contribute
      to the assembly of the 17S U2 snRNP. Finally, we demonstrate that all domains
      required for interactions within the SF3a heterotrimer and the formation of the
      17S U2 snRNP are also necessary to assemble the prespliceosome.

PMID- 11533231
TI  - The basic helix-loop-helix transcription factor Cph2 regulates hyphal development
      in Candida albicans partly via TEC1.
AB  - Candida albicans undergoes a morphogenetic switch from budding yeast to hyphal
      growth form in response to a variety of stimuli and growth conditions. Multiple
      signaling pathways, including a Cph1-mediated mitogen-activated protein kinase
      pathway and an Efg1-mediated cyclic AMP/protein kinase A pathway, regulate the
      transition. Here we report the identification of a basic helix-loop-helix
      transcription factor of the Myc subfamily (Cph2) by its ability to promote
      pseudohyphal growth in Saccharomyces cerevisiae. Like sterol response element
      binding protein 1, Cph2 has a Tyr instead of a conserved Arg in the basic DNA
      binding region. Cph2 regulates hyphal development in C. albicans, as cph2/cph2
      mutant strains show medium-specific impairment in hyphal development and in the
      induction of hypha-specific genes. However, many hypha-specific genes do not have
      potential Cph2 binding sites in their upstream regions. Interestingly, upstream
      sequences of all known hypha-specific genes are found to contain potential
      binding sites for Tec1, a regulator of hyphal development. Northern analysis
      shows that TEC1 transcription is highest in the medium in which cph2/cph2
      displays a defect in hyphal development, and Cph2 is necessary for this
      transcriptional induction of TEC1. In vitro gel mobility shift experiments show
      that Cph2 directly binds to the two sterol regulatory element 1-like elements
      upstream of TEC1. Furthermore, the ectopic expression of TEC1 suppresses the
      defect of cph2/cph2 in hyphal development. Therefore, the function of Cph2 in
      hyphal transcription is mediated, in part, through Tec1. We further show that
      this function of Cph2 is independent of the Cph1- and Efg1-mediated pathways.

PMID- 11533232
TI  - A novel upstream RNA polymerase III promoter element becomes essential when the
      chromatin structure of the yeast U6 RNA gene is altered.
AB  - The Saccharomyces cerevisiae U6 RNA gene, SNR6, possesses upstream sequences that
      allow productive binding in vitro of the RNA polymerase III (Pol III)
      transcription initiation factor IIIB (TFIIIB) in the absence of TFIIIC or other
      assembly factors. TFIIIC-independent transcription of SNR6 in vitro is highly
      sensitive to point mutations in a consensus TATA box at position -30. In
      contrast, the TATA box is dispensable for SNR6 transcription in vivo, apparently
      because TFIIIC bound to the intragenic A block and downstream B block can recruit
      TFIIIB via protein-protein interactions. A mutant allele of SNR6 with decreased
      spacing between the A and B blocks, snr6-Delta42, exhibits increased dependence
      on the upstream sequences in vivo. Unexpectedly, we find that in vivo expression
      of snr6-Delta42 is much more sensitive to mutations in a (dT-dA)(7) tract between
      the TATA box and transcription start site than to mutations in the TATA box
      itself. Inversion of single base pairs in the center of the dT-dA tract nearly
      abolishes transcription of snr6-Delta42, yet inversion of all 7 base pairs has
      little effect on expression, indicating that the dA-dT tract is relatively
      orientation independent. Although it is within the TFIIIB footprint, point
      mutations in the dT-dA tract do not inhibit TFIIIB binding or TFIIIC-independent
      transcription of SNR6 in vitro. In the absence of the chromatin architectural
      protein Nhp6, dT-dA tract mutations are lethal even when A-to-B block spacing is
      wild type. We conclude that the (dT-dA)(7) tract and Nhp6 cooperate to direct
      productive transcription complex assembly on SNR6 in vivo.

PMID- 11533233
TI  - Translational silencing of ceruloplasmin requires the essential elements of mRNA
      circularization: poly(A) tail, poly(A)-binding protein, and eukaryotic
      translation initiation factor 4G.
AB  - Ceruloplasmin (Cp) is a glycoprotein secreted by the liver and monocytic cells
      and probably plays roles in inflammation and iron metabolism. We showed
      previously that gamma interferon (IFN-gamma) induced Cp synthesis by human U937
      monocytic cells but that the synthesis was subsequently halted by a transcript
      specific translational silencing mechanism involving the binding of a cytosolic
      factor(s) to the Cp mRNA 3' untranslated region (UTR). To investigate how protein
      interactions at the Cp 3'-UTR inhibit translation initiation at the distant 5'
      end, we considered the "closed-loop" model of mRNA translation. In this model,
      the transcript termini are brought together by interactions of poly(A)-binding
      protein (PABP) with both the poly(A) tail and initiation factor eIF4G. The effect
      of these elements on Cp translational control was tested using chimeric reporter
      transcripts in rabbit reticulocyte lysates. The requirement for poly(A) was shown
      since the cytosolic inhibitor from IFN-gamma-treated cells minimally inhibited
      the translation of a luciferase reporter upstream of the Cp 3'-UTR but almost
      completely blocked the translation of a transcript containing a poly(A) tail.
      Likewise, a requirement for poly(A) was shown for silencing of endogenous Cp
      mRNA. We considered the possibility that the cytosolic inhibitor blocked the
      interaction of PABP with the poly(A) tail or with eIF4G. We found that neither of
      these interactions were inhibited, as shown by immunoprecipitation of PABP
      followed by quantitation of the poly(A) tail by reverse transcription-PCR and of
      eIF4G by immunoblot analysis. We considered the alternate possibility that these
      interactions were required for translational silencing. When PABP was depleted
      from the reticulocyte lysate with anti-human PABP antibody, the cytosolic factor
      did not inhibit translation of the chimeric reporter, thus showing the
      requirement for PABP. Similarly, in lysates treated with anti-human eIF4G
      antibody, the cytosolic extract did not inhibit the translation of the chimeric
      reporter, thereby showing a requirement for eIF4G. These data show that
      translational silencing of Cp requires interactions of three essential elements
      of mRNA circularization, poly(A), PABP, and eIF4G. We suggest that Cp mRNA
      circularization brings the cytosolic Cp 3'-UTR-binding factor into the proximity
      of the translation initiation site, where it silences translation by an
      undetermined mechanism. These results suggest that in addition to its important
      function in increasing the efficiency of translation, transcript circularization
      may serve as an essential structural determinant for transcript-specific
      translational control.

PMID- 11533234
TI  - Widespread collaboration of Isw2 and Sin3-Rpd3 chromatin remodeling complexes in
      transcriptional repression.
AB  - The yeast Isw2 chromatin remodeling complex functions in parallel with the Sin3
      Rpd3 histone deacetylase complex to repress early meiotic genes upon recruitment
      by Ume6p. For many of these genes, the effect of an isw2 mutation is partially
      masked by a functional Sin3-Rpd3 complex. To identify the full range of genes
      repressed or activated by these factors and uncover hidden targets of Isw2
      dependent regulation, we performed full genome expression analyses using cDNA
      microarrays. We find that the Isw2 complex functions mainly in repression of
      transcription in a parallel pathway with the Sin3-Rpd3 complex. In addition to
      Ume6 target genes, we find that many Ume6-independent genes are derepressed in
      mutants lacking functional Isw2 and Sin3-Rpd3 complexes. Conversely, we find that
      ume6 mutants, but not isw2 sin3 or isw2 rpd3 double mutants, have reduced
      fidelity of mitotic chromosome segregation, suggesting that one or more functions
      of Ume6p are independent of Sin3-Rpd3 and Isw2 complexes. Chromatin structure
      analyses of two nonmeiotic genes reveals increased DNase I sensitivity within
      their regulatory regions in an isw2 mutant, as seen previously for one meiotic
      locus. These data suggest that the Isw2 complex functions at Ume6-dependent and 
      independent loci to create DNase I-inaccessible chromatin structure by regulating
      the positioning or placement of nucleosomes.

PMID- 11533235
TI  - Mitogen-activated protein kinase p38 controls the expression and
      posttranslational modification of tristetraprolin, a regulator of tumor necrosis
      factor alpha mRNA stability.
AB  - Signal transduction pathways regulate gene expression in part by modulating the
      stability of specific mRNAs. For example, the mitogen-activated protein kinase
      (MAPK) p38 pathway mediates stabilization of tumor necrosis factor alpha (TNF
      alpha) mRNA in myeloid cells stimulated with bacterial lipopolysaccharide (LPS).
      The zinc finger protein tristetraprolin (TTP) is expressed in response to LPS and
      regulates the stability of TNF-alpha mRNA. We show that stimulation of RAW264.7
      mouse macrophages with LPS induces the binding of TTP to the TNF-alpha 3'
      untranslated region. The p38 pathway is required for the induction of TNF-alpha
      RNA-binding activity and for the expression of TTP protein and mRNA. Following
      stimulation with LPS, TTP is expressed in multiple, differentially phosphorylated
      forms. We present evidence that phosphorylation of TTP is mediated by the p38
      regulated kinase MAPKAPK2 (MAPK-activated protein kinase 2). Our findings
      demonstrate a direct link between a specific signal transduction pathway and a
      specific RNA-binding protein, both of which are known to regulate TNF-alpha gene
      expression at a posttranscriptional level.

PMID- 11533236
TI  - ETO, a target of t(8;21) in acute leukemia, makes distinct contacts with multiple
      histone deacetylases and binds mSin3A through its oligomerization domain.
AB  - t(8;21) and t(16;21) create two fusion proteins, AML-1-ETO and AML-1-MTG16,
      respectively, which fuse the AML-1 DNA binding domain to putative transcriptional
      corepressors, ETO and MTG16. Here, we show that distinct domains of ETO contact
      the mSin3A and N-CoR corepressors and define two binding sites within ETO for
      each of these corepressors. In addition, of eight histone deacetylases (HDACs)
      tested, only the class I HDACs HDAC-1, HDAC-2, and HDAC-3 bind ETO. However,
      these HDACs bind ETO through different domains. We also show that the murine
      homologue of MTG16, ETO-2, is also a transcriptional corepressor that works
      through a similar but distinct mechanism. Like ETO, ETO-2 interacts with N-CoR,
      but ETO-2 fails to bind mSin3A. Furthermore, ETO-2 binds HDAC-1, HDAC-2, and HDAC
      3 but also interacts with HDAC-6 and HDAC-8. In addition, we show that expression
      of AML-1-ETO causes disruption of the cell cycle in the G(1) phase. Disruption of
      the cell cycle required the ability of AML-1-ETO to repress transcription because
      a mutant of AML-1-ETO, Delta469, which removes the majority of the corepressor
      binding sites, had no phenotype. Moreover, treatment of AML-1-ETO-expressing
      cells with trichostatin A, an HDAC inhibitor, restored cell cycle control. Thus,
      AML-1-ETO makes distinct contacts with multiple HDACs and an HDAC inhibitor
      biologically inactivates this fusion protein.

PMID- 11533237
TI  - Transcriptional repression by the retinoblastoma protein through the recruitment
      of a histone methyltransferase.
AB  - The E2F transcription factor controls the cell cycle-dependent expression of many
      S-phase-specific genes. Transcriptional repression of these genes in G(0) and at
      the beginning of G(1) by the retinoblasma protein Rb is crucial for the proper
      control of cell proliferation. Rb has been proposed to function, at least in
      part, through the recruitment of histone deacetylases. However, recent results
      indicate that other chromatin-modifying enzymes are likely to be involved. Here,
      we show that Rb also interacts with a histone methyltransferase, which
      specifically methylates K9 of histone H3. The results of coimmunoprecipitation
      experiments of endogenous or transfected proteins indicate that this histone
      methyltransferase is the recently described heterochromatin-associated protein
      Suv39H1. Interestingly, phosphorylation of Rb in vitro as well as in vivo
      abolished the Rb-Suv39H1 interaction. We also found that Suv39H1 and Rb cooperate
      to repress E2F activity and that Suv39H1 could be recruited to E2F1 through its
      interaction with Rb. Taken together, these data indicate that Suv39H1 is involved
      in transcriptional repression by Rb and suggest an unexpected link between E2F
      regulation and heterochromatin.

PMID- 11533239
TI  - Intergenic transcription in the human beta-globin gene cluster.
AB  - Our previous studies on nascent transcription across the human beta-globin gene
      cluster revealed the presence of intergenic transcripts in addition to the
      expected genic transcripts. We now show that transcription into the beta-globin
      locus control region (LCR) begins within an ERV9 endogenous retroviral long
      terminal repeat upstream of DNase I hypersensitive site 5. However, in a
      transgenic mouse, which has the human beta-globin LCR but lacks the ERV9 LTR,
      transcription begins upstream of the transgenic locus. We postulate that in this
      transgenic mouse nearby endogenous mouse promoters are activated by the LCR.
      Intergenic transcription is also detected across the whole transgenic globin gene
      locus independently of the stage of erythroid development. Intergenic
      transcription in the beta-globin cluster is erythroid specific; however, it can
      be induced in nonerythroid cells by several means: by transinduction with a
      plasmid transcribing part of the cluster, by exogenous addition of transcription
      factors, and by treatment with the histone deacetylase inhibitor trichostatin A.

PMID- 11533238
TI  - Histone deacetylase activity represses gamma interferon-inducible HLA-DR gene
      expression following the establishment of a DNase I-hypersensitive chromatin
      conformation.
AB  - Expression of the retinoblastoma tumor suppressor protein (Rb) is required for
      gamma interferon (IFN-gamma)-inducible major histocompatibility complex class II
      gene expression and transcriptionally productive HLA-DRA promoter occupancy in
      several human tumor cell lines. Treatment of these Rb-defective tumor cell lines
      with histone deacetylase (HDAC) inhibitors rescued IFN-gamma-inducible HLA-DRA
      and -DRB mRNA and cell surface protein expression, demonstrating repression of
      these genes by endogenous cellular HDAC activity. Additionally, Rb-defective,
      transcriptionally incompetent tumor cells retained the HLA-DRA promoter DNase I
      hypersensitive site. Thus, HDAC-mediated repression of the HLA-DRA promoter
      occurs following the establishment of an apparent nucleosome-free promoter region
      and before transcriptionally productive occupancy of the promoter by the required
      transactivators. Repression of HLA-DRA promoter activation by HDAC activity
      likely involves a YY1 binding element located in the first exon of the HLA-DRA
      gene. Chromatin immunoprecipitation experiments localized YY1 to the HLA-DRA gene
      in Rb-defective tumor cells. Additionally, mutation of the YY1 binding site
      prevented repression of the promoter by HDAC1 and partially prevented activation
      of the promoter by trichostatin A. Mutation of the octamer element also
      significantly reduced the ability of HDAC1 to confer repression of inducible HLA
      DRA promoter activation. Treatment of Rb-defective tumor cells with HDAC
      inhibitors greatly reduced the DNA binding activity of Oct-1, a repressor of
      inducible HLA-DRA promoter activation. These findings represent the first
      evidence that HDAC activity can repress IFN-gamma-inducible HLA class II gene
      expression and also demonstrate that HDAC activity can contribute to promoter
      repression following the establishment of a DNase I-hypersensitive chromatin
      conformation.

PMID- 11533240
TI  - Transcriptional coregulation by the cell integrity mitogen-activated protein
      kinase Slt2 and the cell cycle regulator Swi4.
AB  - In Saccharomyces cerevisiae, the heterodimeric transcription factor SBF (for SCB
      binding factor) is composed of Swi4 and Swi6 and activates gene expression at the
      G(1)/S-phase transition of the mitotic cell cycle. Cell cycle commitment is
      associated not only with major alterations in gene expression but also with
      highly polarized cell growth; the mitogen-activated protein kinase (MAPK) Slt2 is
      required to maintain cell wall integrity during periods of polarized growth and
      cell wall stress. We describe experiments aimed at defining the regulatory
      pathway involving the cell cycle transcription factor SBF and Slt2-MAPK. Gene
      expression assays and chromatin immunoprecipitation experiments revealed Slt2
      dependent recruitment of SBF to the promoters of the G(1) cyclins PCL1 and PCL2
      after activation of the Slt2-MAPK pathway. We performed DNA microarray analysis
      and identified other genes whose expression was reduced in both SLT2 and SWI4
      deletion strains. Genes that are sensitive to both Slt2 and Swi4 appear to be
      uniquely regulated and reveal a role for Swi4, the DNA-binding component of SBF,
      which is independent of the regulatory subunit Swi6. Some of the Swi4- and Slt2
      dependent genes do not require Swi6 for either their expression or for Swi4
      localization to their promoters. Consistent with these results, we found a direct
      interaction between Swi4 and Slt2. Our results establish a new Slt2-dependent
      mode of Swi4 regulation and suggest roles for Swi4 beyond its prominent role in
      controlling cell cycle transcription.

PMID- 11533241
TI  - Human MCF10A mammary epithelial cells undergo apoptosis following actin
      depolymerization that is independent of attachment and rescued by Bcl-2.
AB  - Many tumor cells are impaired in adhesion-regulated apoptosis, which contributes
      to their metastatic potential. However, suppression of this apoptotic pathway in
      untransformed cells is not mediated only by adhesion to the extracellular matrix
      but also through the resulting ability to spread and adopt a distinct morphology.
      Since cell spreading is dependent on the integrity of the actin microfilament
      cytoskeleton, we sought to determine if actin depolymerization was sufficient to
      induce apoptosis, even in the presence of continuous attachment. For this study,
      we used a human mammary epithelial cell line (MCF10A), which is immortalized but
      remains adhesion dependent for survival. Treatment of MCF10A cells with
      latrunculin-A (LA), an inhibitor of actin polymerization, rapidly led to
      disruption of the actin cytoskeleton and caused cell rounding but preserved
      attachment. Initiation of apoptosis in LA-treated MCF10A cells was detected by
      mitochondrial localization of the Bax apoptotic protein, which was prevented by
      overexpression of Bcl-2. DNA fragmentation and poly(ADP-ribose) polymerase (PARP)
      cleavage in LA-treated MCF10A cells indicated progression to the execution phase
      of apoptosis. The MDA-MB-453 cell line, which was derived from a metastatic human
      mammary tumor, was resistant to PARP cleavage and loss of viability in response
      to actin depolymerization. Stable overexpression of Bcl-2 in the untransformed
      MCF10A cells was able to recapitulate the resistance to apoptosis found in the
      tumor cell line. We demonstrate that inhibition of actin polymerization is
      sufficient to stimulate apoptosis in attached MCF10A cells, and we present a
      novel role for Bcl-2 in cell death induced by direct disruption of the actin
      cytoskeleton.

PMID- 11533242
TI  - Creation of a pluripotent ubiquitin-conjugating enzyme.
AB  - We describe the creation of a pluripotent ubiquitin-conjugating enzyme (E2)
      generated through a single amino acid substitution within the catalytic domain of
      RAD6 (UBC2). This RAD6 derivative carries out the stress-related function of UBC4
      and the cell cycle function of CDC34 while maintaining its own DNA repair
      function. Furthermore, it carries out CDC34's function in the absence of the
      CDC34 carboxy-terminal extension. By using sequence and structural comparisons,
      the residues that define the unique functions of these three E2s were found on
      the E2 catalytic face partitioned to either side by a conserved divide. One of
      these patches corresponds to a binding site for both HECT and RING domain
      proteins, suggesting that a single substitution in the catalytic domain of RAD6
      confers upon it the ability to interact with multiple ubiquitin protein ligases
      (E3s). Other amino acid substitutions made within the catalytic domain of RAD6
      either caused loss of its DNA repair function or modified its ability to carry
      out multiple E2 functions. These observations suggest that while HECT and RING
      domain binding may generally be localized to a specific patch on the E2 surface,
      other regions of the functional E2 face also play a role in specificity. Finally,
      these data also indicate that RAD6 uses a different functional region than either
      UBC4 or CDC34, allowing it to acquire the functions of these E2s while
      maintaining its own. The pluripotent RAD6 derivative, coupled with sequence,
      structural, and phylogenetic data, suggests that E2s have diverged from a common
      multifunctional progenitor.

PMID- 11533243
TI  - The ornithine decarboxylase gene is essential for cell survival during early
      murine development.
AB  - Overexpression and inhibitor studies have suggested that the c-Myc target gene
      for ornithine decarboxylase (ODC), the enzyme which converts ornithine to
      putrescine, plays an important role in diverse biological processes, including
      cell growth, differentiation, transformation, and apoptosis. To explore the
      physiological function of ODC in mammalian development, we generated mice
      harboring a disrupted ODC gene. ODC-heterozygous mice were viable, normal, and
      fertile. Although zygotic ODC is expressed throughout the embryo prior to
      implantation, loss of ODC did not block normal development to the blastocyst
      stage. Embryonic day E3.5 ODC-deficient embryos were capable of uterine
      implantation and induced maternal decidualization yet failed to develop
      substantially thereafter. Surprisingly, analysis of ODC-deficient blastocysts
      suggests that loss of ODC does not affect cell growth per se but rather is
      required for survival of the pluripotent cells of the inner cell mass. Therefore,
      ODC plays an essential role in murine development, and proper homeostasis of
      polyamine pools appears to be required for cell survival prior to gastrulation.

PMID- 11533244
TI  - Intrachromatid excision of telomeric DNA as a mechanism for telomere size control
      in Saccharomyces cerevisiae.
AB  - We have previously identified a process in the yeast Saccharomyces cerevisiae
      that results in the contraction of elongated telomeres to wild-type length within
      a few generations. We have termed this process telomeric rapid deletion (TRD). In
      this study, we use a combination of physical and genetic assays to investigate
      the mechanism of TRD. First, to distinguish among several recombinational and
      nucleolytic pathways, we developed a novel physical assay in which HaeIII
      restriction sites are positioned within the telomeric tract. Specific telomeres
      were subsequently tested for HaeIII site movement between telomeres and for
      HaeIII site retention during TRD. Second, genetic analyses have demonstrated that
      mutations in RAD50 and MRE11 inhibit TRD. TRD, however, is independent of the
      Rap1p C-terminal domain, a central regulator of telomere size control. Our
      results provide evidence that TRD is an intrachromatid deletion process in which
      sequences near the extreme terminus invade end-distal sequences and excise the
      intervening sequences. We propose that the Mre11p-Rad50p-Xrs2p complex prepares
      the invading telomeric overhang for strand invasion, possibly through end
      processing or through alterations in chromatin structure.

PMID- 11533245
TI  - Interaction between the Drosophila CAF-1 and ASF1 chromatin assembly factors.
AB  - The assembly of newly synthesized DNA into chromatin is essential for normal
      growth, development, and differentiation. To gain a better understanding of the
      assembly of chromatin during DNA synthesis, we identified, cloned, and
      characterized the 180- and 105-kDa polypeptides of Drosophila chromatin assembly
      factor 1 (dCAF-1). The purified recombinant p180+p105+p55 dCAF-1 complex is
      active for DNA replication-coupled chromatin assembly. Furthermore, we have
      established that the putative 75-kDa polypeptide of dCAF-1 is a C-terminally
      truncated form of p105 that does not coexist in dCAF-1 complexes containing the
      p105 subunit. The analysis of native and recombinant dCAF-1 revealed an
      interaction between dCAF-1 and the Drosophila anti-silencing function 1 (dASF1)
      component of replication-coupling assembly factor (RCAF). The binding of dASF1 to
      dCAF-1 is mediated through the p105 subunit of dCAF-1. Consistent with the
      interaction between dCAF-1 p105 and dASF1 in vitro, we observed that dASF1 and
      dCAF-1 p105 colocalized in vivo in Drosophila polytene chromosomes. This
      interaction between dCAF-1 and dASF1 may be a key component of the functional
      synergy observed between RCAF and dCAF-1 during the assembly of newly synthesized
      DNA into chromatin.

PMID- 11533246
TI  - Polycomb group repression reduces DNA accessibility.
AB  - The Polycomb group proteins are responsible for long-term repression of a number
      of genes in Drosophila melanogaster, including the homeotic genes of the bithorax
      complex. The Polycomb protein is thought to alter the chromatin structure of its
      target genes, but there has been little direct evidence for this model. In this
      study, the chromatin structure of the bithorax complex was probed with three
      separate assays for DNA accessibility: (i) activation of polymerase II (Pol II)
      transcription by Gal4, (ii) transcription by the bacteriophage T7 RNA polymerase
      (T7RNAP), and (iii) FLP-mediated site-specific recombination. All three processes
      are restricted or blocked in Polycomb-repressed segments. In contrast, control
      test sites outside of the bithorax complex permitted Gal4, T7RNAP, and FLP
      activities throughout the embryo. Several P insertions in the bithorax complex
      were tested, providing evidence that the Polycomb-induced effect is widespread
      over target genes. This accessibility effect is similar to that seen for SIR
      silencing in Saccharomyces cerevisiae. In contrast to SIR silencing, however,
      episomes excised from Polycomb-repressed chromosomal sites do not show an altered
      superhelix density.

PMID- 11533247
TI  - HMG proteins and DNA flexibility in transcription activation.
AB  - The relative stiffness of naked DNA is evident from measured values of
      longitudinal persistence length (approximately 150 bp) and torsional persistence
      length (approximately 180 bp). These parameters predict that certain arrangements
      of eukaryotic transcription activator proteins in gene promoters should be much
      more effective than others in fostering protein-protein interactions with the
      basal RNA polymerase II transcription apparatus. Thus, if such interactions
      require some kind of DNA looping, DNA loop energies should depend sensitively on
      helical phasing of protein binding sites, loop size, and intrinsic DNA curvature
      within the loop. Using families of artificial transcription templates where these
      parameters were varied, we were surprised to find that the degree of
      transcription activation by arrays of Gal4-VP1 transcription activators in HeLa
      cell nuclear extract was sensitive only to the linear distance separating a basal
      promoter from an array of bound activators on DNA templates. We now examine the
      hypothesis that this unexpected result is due to factors in the extract that act
      to enhance apparent DNA flexibility. We demonstrate that HeLa cell nuclear
      extract is rich in a heat-resistant activity that dramatically enhances apparent
      DNA longitudinal and torsional flexibility. Recombinant mammalian high-mobility
      group 2 (HMG-2) protein can substitute for this activity. We propose that the
      abundance of HMG proteins in eukaryotic nuclei provides an environment in which
      DNA is made sufficiently flexible to remove many constraints on protein binding
      site arrangements that would otherwise limit efficient transcription activation
      to certain promoter geometries.

PMID- 11533248
TI  - Targeting of the yeast Ty5 retrotransposon to silent chromatin is mediated by
      interactions between integrase and Sir4p.
AB  - The Ty5 retrotransposons of Saccharomyces cerevisiae integrate preferentially
      into regions of silent chromatin at the telomeres and silent mating loci (HMR and
      HML). We define a Ty5-encoded targeting domain that spans 6 amino acid residues
      near the C terminus of integrase (LXSSXP). The targeting domain establishes
      silent chromatin when it is tethered to a weakened HMR-E silencer, and it
      disrupts telomeric silencing when it is overexpressed. As determined by both
      yeast two-hybrid and in vitro binding assays, the targeting domain interacts with
      the C terminus of Sir4p, a structural component of silent chromatin. This
      interaction is abrogated by mutations in the targeting domain that disrupt
      integration into silent chromatin, suggesting that recognition of Sir4p by the
      targeting domain is the primary determinant in Ty5 target specificity.

PMID- 11533249
TI  - Tissue-specific autoregulation of the stat3 gene and its role in interleukin-6
      induced survival signals in T cells.
AB  - Signal transducer and activator of transcription 3 (STAT3) mediates signals of
      various growth factors and cytokines, including interleukin-6 (IL-6). In certain
      IL-6-responsive cell lines, the stat3 gene is autoregulated by STAT3 through a
      composite IL-6 response element in its promoter that contains a STAT3-binding
      element (SBE) and a cyclic AMP-responsive element. To reveal the nature and roles
      of the stat3 autoregulation in vivo, we generated mice that harbor a mutation in
      the SBE (stat3(mSBE)). The intact SBE was crucial for IL-6-induced stat3 gene
      activation in the spleen, especially in the red pulp region, the kidney, and both
      mature and immature T lymphocytes. The SBE was not required, however, for IL-6
      induced stat3 gene activation in hepatocytes. T lymphocytes from the
      stat3(mSBE/mSBE) mice were more susceptible to apoptosis despite the presence of
      IL-6 than those from wild-type mice. Consistent with this, IL-6-dependent
      activation of the Pim-1 and junB genes, direct target genes for STAT3, was
      attenuated in T lymphocytes of the stat3(mSBE/mSBE) mice. Thus, the tissue
      specific autoregulation of the stat3 gene operates in vivo and plays a role in IL
      6-induced antiapoptotic signaling in T cells.

PMID- 11533250
TI  - Silencing of Wnt signaling and activation of multiple metabolic pathways in
      response to thyroid hormone-stimulated cell proliferation.
AB  - To investigate the transcriptional program underlying thyroid hormone (T3)
      induced cell proliferation, cDNA microarrays were used to survey the temporal
      expression profiles of 4,400 genes. Of 358 responsive genes identified, 88% had
      not previously been reported to be transcriptionally or functionally modulated by
      T3. Partitioning the genes into functional classes revealed the activation of
      multiple pathways, including glucose metabolism, biosynthesis, transcriptional
      regulation, protein degradation, and detoxification in T3-induced cell
      proliferation. Clustering the genes by temporal expression patterns provided
      further insight into the dynamics of T3 response pathways. Of particular
      significance was the finding that T3 rapidly repressed the expression of key
      regulators of the Wnt signaling pathway and suppressed the transcriptional
      downstream elements of the beta-catenin-T-cell factor complex. This was confirmed
      biochemically, as beta-catenin protein levels also decreased, leading to a
      decrease in the transcriptional activity of a beta-catenin-responsive promoter.
      These results indicate that T3-induced cell proliferation is accompanied by a
      complex coordinated transcriptional reprogramming of many genes in different
      pathways and that early silencing of the Wnt pathway may be critical to this
      event.

PMID- 11533251
TI  - B-cell receptor- and phorbol ester-induced NF-kappaB and c-Jun N-terminal kinase
      activation in B cells requires novel protein kinase C's.
AB  - Antigen receptor signaling is known to activate NF-kappaB in lymphocytes. While T
      cell-receptor-induced NF-kappaB activation critically depends on novel protein
      kinase C theta (PKCtheta), the role of novel PKCs in B-cell stimulation has not
      been elucidated. In primary murine splenic B cells, we found high expression of
      the novel PKCs delta and epsilon but only weak expression of the theta isoform.
      Rottlerin blocks phorbol ester (phorbol myristate acetate [PMA])- or B-cell
      receptor (BCR)-mediated NF-kappaB and c-Jun N-terminal kinase (JNK) activation in
      primary B and T cells to a similar extent, suggesting that novel PKCs are
      positive regulators of signaling in hematopoietic cells. Mouse 70Z/3 pre-B cells
      have been widely used as a model for NF-kappaB activation in B cells. Similar to
      the situation in splenic B cells, rottlerin inhibits BCR and PMA stimulation of
      NF-kappaB in 70Z/3 cells. A derivative of 70Z/3 cells, 1.3E2 cells, are defective
      in NF-kappaB activation due to the lack of the IkappaB kinase (IKKgamma) protein.
      Ectopic expression of IKKgamma can rescue NF-kappaB activation in response to
      lipopolysaccharides (LPS) and interleukin-1beta (IL-1beta), but not to PMA. In
      addition, PMA-induced activation of the mitogen-activated protein kinase JNK is
      blocked in 1.3E2 cells, suggesting that an upstream component common to both
      pathways is either missing or mutated. Analysis of various PKC isoforms revealed
      that exclusively PKCtheta was absent in 1.3E2 cells while it was expressed in
      70Z/3 cells. Stable expression of either novel PKCtheta or -delta but not
      classical PKCbetaII in 1.3E2 IKKgamma-expressing cells rescues PMA activation of
      NF-kappaB and JNK signaling, demonstrating a critical role of novel PKCs for B
      cell activation.

PMID- 11533252
TI  - Nuclear entry mechanism of rat PER2 (rPER2): role of rPER2 in nuclear
      localization of CRY protein.
AB  - Mammalian PERIOD2 protein (PER2) is the product of a clock gene that controls
      circadian rhythms, because PER2-deficient mice have an arrhythmic phenotype. The
      nuclear entry regulation of clock gene products is a key step in proper circadian
      rhythm formation in both Drosophila and mammals, because the periodic
      transcription of clock genes is controlled by an intracellular, oscillating,
      negative feedback loop. The present study used deletion mutants of rat PER2
      (rPER2) to identify the functional nuclear localization signal (NLS) in rPER2.
      The elimination of putative NLS (residues 778 to 794) from the rPER2 fragment
      resulted in the loss of nuclear entry activity. Adding the NLS to the cytosolic
      protein (bacterial alkaline phosphatase) translocates the fusion protein to the
      nuclei. The data indicate the presence of a functional NLS in rPER2. Furthermore,
      intact rPER2 was preferentially translocated from the cytoplasm to the nucleus
      when coexpressed with human CRY1 (hCRY1). However, rPER2 mutants lacking a
      carboxyl-terminal domain could not enter the nucleus even in the presence of
      hCRY1. In addition, coexpression of the nuclear localization domain (residues 512
      to 794) lacking rPER2 and CRY1 changed the subcellular localization of CRY1 from
      the nucleus to the cytoplasm. In vitro protein interaction studies demonstrated
      that the carboxyl-terminal domain of rPER2 is essential for binding to CRY1. The
      data suggested that both the rPER2 NLS and carboxyl-terminal CRY binding domain
      are essential for nuclear entry of the rPER2-CRY1 complex.

PMID- 11533253
TI  - Recruitment of the class II phosphoinositide 3-kinase C2beta to the epidermal
      growth factor receptor: role of Grb2.
AB  - Previously we demonstrated that the class II phosphoinositide 3-kinase C2beta
      (PI3K-C2beta) is rapidly recruited to a phosphotyrosine signaling complex
      containing the activated receptor for epidermal growth factor (EGF). Although
      this association was shown to be dependent upon specific phosphotyrosine residues
      present on the EGF receptor, the underlying mechanism remained unclear. In this
      study the interaction between PI3K-C2beta and the EGF receptor is competitively
      attenuated by synthetic peptides derived from each of three proline-rich motifs
      present within the N-terminal region of the PI3K. Further, a series of N-terminal
      PI3K-C2beta fragments, truncated prior to each proline-rich region, bound the
      receptor with decreased efficiency. A single proline-rich region was unable to
      mediate receptor association. Finally, an equivalent N-terminal fragment of PI3K
      C2alpha that lacks similar proline-rich motifs was unable to affinity purify the
      activated EGF receptor from cell lysates. Since these findings revealed that the
      interaction between the EGF receptor and PI3K-C2beta is indirect, we sought to
      identify an adaptor molecule that could mediate their association. In addition to
      the EGF receptor, PI3K-C2beta(2-298) also isolated both Shc and Grb2 from A431
      cell lysates. Recombinant Grb2 directly bound PI3K-C2beta in vitro, and this
      effect was reproduced using either SH3 domain expressed as a glutathione S
      transferase (GST) fusion. Interaction with Grb2 dramatically increased the
      catalytic activity of this PI3K. The relevance of this association was confirmed
      when PI3K-C2beta was isolated by coimmunoprecipitation with anti-Grb2 antibody
      from numerous cell lines. Using immobilized, phosphorylated EGF receptor,
      recombinant PI3K-C2beta was only purified in the presence of Grb2. We conclude
      that proline-rich motifs within the N terminus of PI3K-C2beta mediate the
      association of this enzyme with activated EGF receptor and that this interaction
      involves the Grb2 adaptor.

PMID- 11533254
TI  - Molecular genetic dissection of TAF25, an essential yeast gene encoding a subunit
      shared by TFIID and SAGA multiprotein transcription factors.
AB  - We have performed a systematic structure-function analysis of Saccharomyces
      cerevisiae TAF25, an evolutionarily conserved, single-copy essential gene which
      encodes the 206-amino-acid TAF25p protein. TAF25p is an integral subunit of both
      the 15-subunit general transcription factor TFIID and the multisubunit, chromatin
      acetylating transcriptional coactivator SAGA. We used hydroxylamine mutagenesis,
      targeted deletion, alanine-scanning mutagenesis, high-copy suppression methods,
      and two-hybrid screening to dissect TAF25. Temperature-sensitive mutant strains
      generated were used for coimmunoprecipitation and transcription analyses to
      define the in vivo functions of TAF25p. The results of these analyses show that
      TAF25p is comprised of multiple mutable elements which contribute importantly to
      RNA polymerase II-mediated mRNA gene transcription.

PMID- 11533255
TI  - Study of cyclin proteolysis in anaphase-promoting complex (APC) mutant cells
      reveals the requirement for APC function in the final steps of the fission yeast
      septation initiation network.
AB  - Cytokinesis in eukaryotic cells requires the inactivation of mitotic cyclin
      dependent kinase complexes. An apparent exception to this relationship is found
      in Schizosaccharomyces pombe mutants with mutations of the anaphase-promoting
      complex (APC). These conditional lethal mutants arrest with unsegregated
      chromosomes because they cannot degrade the securin, Cut2p. Although failing at
      nuclear division, these mutants septate and divide. Since septation requires
      Cdc2p inactivation in wild-type S. pombe, it has been suggested that Cdc2p
      inactivation occurs in these mutants by a mechanism independent of cyclin
      degradation. In contrast to this prediction, we show that Cdc2p kinase activity
      fluctuates in APC cut mutants due to Cdc13/cyclin B destruction. In APC-null
      mutants, however, septation and cutting do not occur and Cdc13p is stable. We
      conclude that APC cut mutants are hypomorphic with respect to Cdc13p degradation.
      Indeed, overproduction of nondestructible Cdc13p prevents septation in APC cut
      mutants and the normal reorganization of septation initiation network components
      during anaphase.

PMID- 11533258
TI  - Karl August Folkers (1906-1997).

PMID- 11533256
TI  - Functional analysis of the cyclin-dependent kinase inhibitor Pho81 identifies a
      novel inhibitory domain.
AB  - In response to phosphate limitation, Saccharomyces cerevisiae induces
      transcription of a set of genes important for survival. A phosphate-responsive
      signal transduction pathway mediates this response by controlling the activity of
      the transcription factor Pho4. Three components of this signal transduction
      pathway resemble those used to regulate the eukaryotic cell cycle: a cyclin
      dependent kinase (CDK), Pho85; a cyclin, Pho80; and a CDK inhibitor (CKI), Pho81.
      Pho81 forms a stable complex with Pho80-Pho85 under both high- and low-phosphate
      conditions, but it only inhibits the kinase when cells are starved for phosphate.
      Pho81 contains six tandem repeats of the ankyrin consensus domain homologous to
      the INK4 family of mammalian CKIs. INK4 proteins inhibit kinase activity through
      an interaction of the ankyrin repeats and the CDK subunits. Surprisingly, we find
      that a region of Pho81 containing 80 amino acids C terminal to the ankyrin
      repeats is necessary and sufficient for Pho81's CKI function. The ankyrin repeats
      of Pho81 appear to have no significant role in Pho81 inhibition. Our results
      suggest that Pho81 inhibits Pho80-Pho85 with a novel motif.

PMID- 11533259
TI  - Virgil P. Sydenstricker (1889-1964).

PMID- 11533257
TI  - Raf-MEK-Erk cascade in anoikis is controlled by Rac1 and Cdc42 via Akt.
AB  - Signals from the extracellular matrix are essential for the survival of many cell
      types. Dominant-negative mutants of two members of Rho family GTPases, Rac1 and
      Cdc42, mimic the loss of anchorage in primary mouse fibroblasts and are potent
      inducers of apoptosis. This pathway of cell death requires the activation of both
      the p53 tumor suppressor and the extracellular signal-regulated mitogen-activated
      protein kinases (Erks). Here we characterize the proapoptotic Erk signal and show
      that it differs from the classically observed survival-promoting one by the
      intensity of the kinase activation. The disappearance of the GTP-bound forms of
      Rac1 and Cdc42 gives rise to proapoptotic, moderate activation of the Raf-MEK-Erk
      cascade via a signaling pathway involving the kinases phosphatidlyinositol 3
      kinase and Akt. Moreover, concomitant activation of p53 and inhibition of Akt are
      both necessary and sufficient to signal anoikis in primary fibroblasts. Our data
      demonstrate that the GTPases of the Rho family control three major components of
      cellular signal transduction, namely, p53, Akt, and Erks, which collaborate in
      the induction of apoptosis due to the loss of anchorage.

PMID- 11533260
TI  - Oral IGF-I alters the posttranslational processing but not the activity of
      lactase-phlorizin hydrolase in formula-fed neonatal pigs.
AB  - To determine the cellular mechanism whereby oral insulin-like growth factor I
      (IGF-I) increases intestinal lactase-phlorizin hydrolase (LPH) activity, we
      studied 2-d-old pigs fed cow's milk formula (control, n = 5), formula + low IGF-I
      (0.5 mg/L; n = 6) or formula + high IGF-I (12.0 mg/L, n = 6) for 15 d. On d 15,
      intestinal protein synthesis and lactase processing were measured in vivo in fed
      pigs using a 6-h intravenous, overlapping infusion of multiple stable isotopes
      (2H(3)-Leu, 13C(1)-Leu, 13C(1)-Phe, 2H(5)-Phe, 13C(6)-Phe and 13C(9)-Phe).
      Morphometry and cell proliferation also were measured in the jejunum and ileum.
      Neither dose of IGF-I affected the masses of wet tissue, protein or DNA, or the
      villus height, cell proliferation or LPH-specific activity. Oral IGF-I decreased
      the synthesis and abundance of prolactase-phlorizin hydrolase (pro-LPH), but
      increased brush-border (BB)-LPH synthesis in the ileum. The BB-LPH processing
      efficiency was twofold to threefold greater in IGF-fed than in control pigs. In
      all pigs, villus height and the total mucosal and specific activity of LPH
      activity were greater in the ileum than in the jejunum, yet the synthesis of BB
      LPH were significantly lower in the ileum than in the jejunum. We conclude that
      oral IGF-I increases the processing efficiency of pro-LPH to BB-LPH but does not
      affect LPH activity. Moreover, the posttranslational processing of BB-LPH is
      markedly lower in the ileum than in the jejunum.

PMID- 11533261
TI  - An extract of Lagerstroemia speciosa L. has insulin-like glucose uptake
      stimulatory and adipocyte differentiation-inhibitory activities in 3T3-L1 cells.
AB  - The effects of extracts isolated from Lagerstroemia speciosa L. (banaba) on
      glucose transport and adipocyte differentiation in 3T3-L1 cells were studied.
      Glucose uptake-inducing activity of banaba extract (BE) was investigated in
      differentiated adipocytes using a radioactive assay, and the ability of BE to
      induce differentiation in preadipocytes was examined by Northern and Western blot
      analyses. The hot water BE and the banaba methanol eluent (BME) stimulated
      glucose uptake in 3T3-L1 adipocytes with an induction time and a dose-dependent
      response similar to those of insulin. Furthermore, there were no additive or
      synergistic effects found between BE and insulin on glucose uptake, and the
      glucose uptake activity of insulin could be reduced to basal levels by adding
      increasing amounts of BE. Unlike insulin, BE did not induce adipocyte
      differentiation in the presence of 3-isobutyl-1-methylxanthine (IBMX) and
      dexamethasone (DEX). BE inhibited the adipocyte differentiation induced by
      insulin plus IBMX and DEX (IS-IBMX-DEX) of 3T3-L1 preadipocytes in a dose
      dependent manner. The differences in the glucose uptake and differentiation
      inhibitory activities between untreated cells and those treated with BE were
      significant (P < 0.01). The inhibitory activity was further demonstrated by
      drastic reductions of peroxisome proliferator-activated receptor gamma2
      (PPARgamma2) mRNA and glucose transporter-4 (GLUT4) protein in cells induced from
      preadipocytes with IS-IBMX-DEX in the presence of BE. The unique combination of a
      glucose uptake stimulatory activity, the absence of adipocyte differentiation
      activity and effective inhibition of adipocyte differentiation induced by IS-IBMX
      DEX in 3T3-L1 cells suggest that BE may be useful for prevention and treatment of
      hyperglycemia and obesity in type II diabetics.

PMID- 11533262
TI  - Theaflavins in black tea and catechins in green tea are equally effective
      antioxidants.
AB  - Green tea catechins, including (-)-epicatechin (EC), (-)-epicatechin gallate
      (ECG), (-)-epigallocatechin (EGC) and (-)-epigallocatechin gallate (EGCG), are
      oxidized and dimerized during the manufacture of black tea and oolong tea to form
      orange-red pigments, theaflavins (TF), a mixture of theaflavin (TF1), theaflavin
      3-gallate (TF2A), theaflavin-3'-gallate (TF2B) and theaflavin-3,3'-digallate
      (TF3). The present study was designed to compare the antioxidant activities of
      individual TF with that of each catechin using human LDL oxidation as a model.
      All catechins and TF tested inhibited Cu(+2)-mediated LDL oxidation. Analysis of
      the thiobarbituric acid-reactive substances (TBARS) and conjugated dienes
      produced during LDL oxidation revealed that the antioxidant activity was in the
      order: TF3 > ECG > EGCG > or = TF2B > or = TF2A > TF1 > or = EC > EGC. Four TF
      derivatives also demonstrated a dose-dependent antioxidant activity in Cu(+2)
      mediated LDL oxidation at concentrations of 5-40 micromol/L. These results
      demonstrate that the TF present in black tea possess at least the same
      antioxidant potency as catechins present in green tea, and that the conversion of
      catechins to TF during fermentation in making black tea does not alter
      significantly their free radical-scavenging activity.

PMID- 11533263
TI  - Exercise down-regulates hepatic fatty acid synthase in streptozotocin-treated
      rats.
AB  - An acute bout of prolonged exercise has been shown to decrease hepatic fatty acid
      synthase (FAS) mRNA and activity induced by high carbohydrate diets. The purpose
      of the current study was to examine the role of insulin in this exercise down
      regulation of FAS. Sixty-four male Wistar rats were randomly divided into normal
      and streptozotocin (STZ)-treated diabetic groups. After being starved for 48 h
      and refed a high cornstarch (C) or fructose (F) diet for 10 h, one half of each
      group of rats was killed after an acute bout of prolonged exercise (E), while the
      other half of the group was killed in the rested state. STZ treatment suppressed
      plasma insulin and elevated plasma glucagon levels along with a severe
      hyperglycemia. FAS mRNA levels decreased by 60% (P < 0.05) with STZ treatment but
      were 250% higher in F-fed versus C-fed rats. E abolished F-induced FAS mRNA
      levels in both normal and STZ rats and decreased plasma glucose concentration in
      STZ rats (P < 0.05). F-fed normal rats showed twofold higher hepatic FAS activity
      than did C-fed normal rats and this dietary induction was abolished by STZ (P <
      0.05). FAS activity in normal rats was not affect by E and was increased with E
      in STZ rats. Nuclear protein binding to the insulin response sequence was not
      affected by STZ or diet and increased with E (P < 0.05). Carbohydrate response
      element binding was greater with F- versus C-feeding (P < 0.05) but unaffected by
      E. E enhanced inverted CCAAT-box element binding regardless of diet and STZ. We
      conclude that although insulin status had a great influence on FAS gene
      expression, E-induced down-regulation of FAS mRNA was not mediated by altered
      insulin response sequence binding but primarily by increased inverted CCAAT-box
      element binding to the FAS promoter and/or decreased concentration of
      carbohydrate metabolites.

PMID- 11533264
TI  - Targeted disruption of stearoyl-CoA desaturase1 gene in mice causes atrophy of
      sebaceous and meibomian glands and depletion of wax esters in the eyelid.
AB  - Stearoyl-CoA desaturase (SCD) is a microsomal rate-limiting enzyme in the
      cellular synthesis of monounsaturated fatty acids (MUFA), mainly oleate (18:1)
      and palmitoleate (16:1), which are the major MUFA of membrane phospholipids,
      cholesterol esters and triglycerides. Three well-characterized isoforms of SCD,
      SCD1, SCD2 and SCD3, exist in mice. To investigate the physiologic functions of
      SCD1, we generated SCD1 null (SCD1-/-) mice. The skin and eyelid of SCD1-/- mice
      are deficient in triglycerides and cholesterol esters, and the eyelid also is
      deficient in wax esters. Furthermore, the eyelid and skin of SCD1-/- mice have
      higher levels of free cholesterol. SCD1-/- mice develop cutaneous abnormalities
      and narrow eye fissure with atrophic sebaceous and meibomian glands. Consumption
      of diets containing high levels of oleate, failed to restore the levels of
      triglycerides, cholesterol esters and wax esters in SCD1-/- mice to the levels
      found in the eyelid of wild-type mice. These results reveal a physiologic role of
      SCD in cholesterol homeostasis as well as in the de novo biosynthesis of
      cholesterol esters, triglycerides and wax esters required for normal skin and
      eyelid function.

PMID- 11533265
TI  - Dietary protein concentration regulates the mRNA expression of chicken hepatic
      malic enzyme.
AB  - Chicken hepatic malic enzyme activity varies with dietary protein content. The
      mechanisms responsible for this alteration in activity are unclear. In a series
      of four experiments, broiler chicks were allowed free access for 1.5, 3, 6 or 24
      h to a low (13 g/100 g diet), basal (22 g/100 g diet) or high (40 g/100 g diet)
      protein diet. The diets were isocaloric and had equal concentrations of dietary
      fat. Hepatic malic enzyme mRNA expression and enzyme activity as well as total
      liver lipid concentration were examined for each experimental duration. There
      were no differences in the expression of the mRNA for malic enzyme at 1.5 h, but
      at 3, 6 and 24 h, malic enzyme mRNA expression was significantly (P < 0.05)
      reduced in chicks fed the high protein diet and significantly enhanced in chicks
      fed the low protein diet compared with chicks fed the basal diet. Hepatic malic
      enzyme activities and total lipid concentration were not different among the
      chicks fed the different diets at 1.5 and 3 h. At 6 and 24 h, malic enzyme
      activity and total liver lipid concentration were both significantly greater in
      birds fed the low protein diet compared with levels in the birds fed the other
      two diets. In birds fed the high protein diet, malic enzyme activity and total
      liver lipid concentration were significantly reduced at 24 h compared with birds
      fed the basal diet. In a final experiment, the observed differences in malic
      enzyme mRNA expression at 6 h were confirmed when chicks were given access to
      isocaloric diets with the same protein levels as the initial 4 experiments, but
      with the dietary concentration of carbohydrate held constant. The results suggest
      that previously observed alterations in the activity of malic enzyme, which were
      correlated with dietary protein intake, are due to rapid changes in the mRNA
      expression of this enzyme.

PMID- 11533266
TI  - A monounsaturated fatty acid-rich pecan-enriched diet favorably alters the serum
      lipid profile of healthy men and women.
AB  - Frequent consumption of nuts is associated with decreased risk of cardiovascular
      disease. We investigated the effect of pecans rich in monounsaturated fat as an
      alternative to the Step 1 diet in modifying serum lipids and lipoproteins in men
      and women with normal to moderately high serum cholesterol. In a single-blind,
      randomized, controlled, crossover feeding study, we assigned 23 subjects (mean
      age: 38 y; 9 women, 14 men) to follow two diets, each for 4 wk: a Step I diet and
      a pecan-enriched diet (accomplished by proportionately reducing all food items in
      a Step I diet by one fifth for a 20% isoenergetic replacement with pecans). The
      percentage of energy from fat in the two diets was 28.3 and 39.6%, respectively.
      Both diets improved the lipid profile; however, the pecan-enriched diet decreased
      both serum total and LDL cholesterol by 0.32 mmol/L (6.7 and 10.4%, respectively)
      and triglyceride by 0.14 mmol/L (11.1%) beyond the Step I diet, while increasing
      HDL cholesterol by 0.06 mmol/L (2.5 mg/dL). Serum apolipoprotein B and
      lipoprotein(a) decreased by 11.6 and 11.1%, respectively, and apolipoprotein A1
      increased by 2.2% when subjects consumed the pecan compared with the Step I diet.
      These differences were all significant (P < 0.05). A 20% isoenergetic replacement
      of a Step I diet with pecans favorably altered the serum lipid profile beyond the
      Step I diet, without increasing body weight. Nuts such as pecans that are rich in
      monounsaturated fat may therefore be recommended as part of prescribed
      cholesterol-lowering diet of patients or habitual diet of healthy individuals.

PMID- 11533267
TI  - Soy protein intake by perimenopausal women does not affect circulating lipids and
      lipoproteins or coagulation and fibrinolytic factors.
AB  - Soy protein favorably alters serum lipids and lipoproteins in
      hypercholesterolemic individuals, thereby reducing cardiovascular disease risk.
      The primary purpose was to determine the effect of soy protein (40 g/d) on
      circulating lipids and lipoproteins or coagulation and fibrinolytic factors in
      normocholesterolemic and mildly hypercholesterolemic perimenopausal women. We
      also determined the contribution of coagulation and fibrinolytic and other
      factors (e.g., body size and composition; serum estrogens, ferritin, iron;
      dietary intake) to lipid profiles. Subjects were randomly assigned to treatment:
      isoflavone-rich soy (n = 24), isoflavone-poor soy (n = 24), or whey control (n =
      21) protein. We measured circulating lipids and lipoproteins at baseline, wk 12
      and wk 24, and coagulation/fibrinolytic factors at baseline and wk 24.
      Coagulation and fibrinolytic factors were not adversely affected by treatment.
      Treatment did not alter lipid profiles in mildly hypercholesterolemic (n = 30) or
      in all subjects combined. Time significantly (P < 0.001) affected serum total
      cholesterol, triacylglycerol, LDL cholesterol and HDL cholesterol concentrations.
      We could not attribute changes over time to various factors, but at baseline
      accounted for 57% of the variability in HDL cholesterol (P < or = 0.0001) and for
      50% in the total to HDL cholesterol ratio (P < or = 0.0001). Dietary vitamin E
      and % energy from fat had positive effects, whereas plasma plasminogen activator
      inhibitor-1, fibrinogen, body weight and serum ferritin had negative effects on
      HDL and total to HDL cholesterol. Isoflavone-rich or isoflavone-poor soy protein
      had no effect on lipid profiles or coagulation and fibrinolytic factors, whereas
      the effect of time suggested that the hormonal milieu during the menopausal
      transition may have overridden any detectable treatment effect on lipids. The
      relationship between coagulation factors and serum lipids should be examined
      further as indices of cardiovascular disease risk in midlife women.

PMID- 11533268
TI  - Exchangeable zinc pool masses and turnover are maintained in healthy men with low
      zinc intakes.
AB  - Previous studies suggest that rapidly exchanging zinc pools (EZP), thought to
      supply the zinc required by tissues, are smaller and turn over more rapidly in
      individuals with lower zinc intakes. We studied the effects of low dietary zinc
      (4.6 mg/d) on EZP mass and turnover in seven healthy men confined during a 20-wk
      clinical study. Supplements of 9.1 mg zinc were given during the 5-wk baseline
      and repletion periods, and placebos were given during a 10-wk zinc-restriction
      period. Stable 70Zn tracers were administered intravenously at the end of
      baseline, 3 and 10 wk after the start of zinc restriction and at the end of
      repletion. Multiple plasma samples were collected over an 8-d period after tracer
      administration. 70Zn:66Zn ratios were measured using inductively coupled plasma
      mass spectrometry, and tracer-tracee data were analyzed by compartmental
      modeling. Activities of the zinc-dependent enzymes, alkaline phosphatase and
      5'nucleotidase, were unchanged during the study. There were no significant
      changes in EZP masses or kinetic parameters. A three-compartment model indicated
      that the masses of plasma zinc and total EZP averaged 3.25 +/- 0.58 and 147.8 +/-
      33.2 mg, respectively, at the four time points studied. Plasma zinc mass turned
      over at an average of 5.3 times per hour. There was an 11% reduction (P = 0.06)
      in plasma zinc flux 3 wk after the start of the low zinc diet period, but it
      returned to baseline values after 10 wk of zinc restriction. The results suggest
      that total EZP mass is maintained when dietary zinc is reduced to 4.6 mg/d over a
      10-wk period.

PMID- 11533269
TI  - Calcium fractional absorption and metabolism assessed using stable isotopes
      differ between postpartum and never pregnant women.
AB  - Determining the fractional absorption (FA) of calcium using the incorporation
      into urine of stable isotopes given intravenously (IV) and orally has become a
      routine procedure. We investigated the FA of calcium in two groups of (2-3 mo)
      postpartum women lactating (LACT) (n = 6) and nonlactating (PPNL) (n = 6), and in
      never pregnant (NP) women (n = 7). The women consumed a controlled diet
      containing 30-33 mmol/d calcium (Ca) for 21 d. On d 7 of the controlled diet, the
      women received 0.05 mmol of 42Ca IV and 0.25 mmol 44Ca orally in milk. Urine
      samples (24-h) were collected for the next 14 d and morning blood samples were
      collected from fasting subjects before dosing and at 24 and 48 h after receiving
      the isotopes. Milk samples from the LACT women were collected from each feeding
      beginning 24 h before to 72 h after dosing. There were no significant differences
      in the FA of calcium as measured by stable isotope incorporation into urine (23.8
      +/- 2.9%), serum (24.0 +/- 3.4%) or milk (23.6 +/- 3.6%) of LACT women. The
      fractional calcium absorption measured in urine of the postpartum women (LACT and
      PPNL, 23.8 +/- 2.9% and 25.0 +/- 3.3%, respectively) did not differ but was
      greater (P < 0.028) than that of the NP women (17.3 +/- 1.3%). The postpartum
      LACT and PPNL women had a reduced urinary excretion of calcium (P < 0.01)
      compared with the NP women. There was a significantly greater incorporation (P <
      0.001) by LACT women of the oral isotope dose into milk than into urine. Calcium
      FA can be determined from incorporation of stable isotopes into breast milk and
      serum as well as urine.

PMID- 11533270
TI  - Fish oil (n-3) polyunsaturated fatty acids beneficially affect biliary
      cholesterol nucleation time in obese women losing weight.
AB  - It has been reported that intake of (n-3) polyunsaturated fatty acids (PUFA)
      reduces the risk of coronary heart disease and decreases biliary cholesterol
      saturation in the bile of gallstone patients. We investigated the effect of n-3
      PUFA on cholesterol saturation index (CSI) and nucleation time (NT) in obese
      subjects who were losing weight. This was a double-blind, placebo-controlled
      clinical trial. Obese women (n = 35) with a body mass index (BMI) > or = 30
      kg/m(2), with no prior history of gallstones or cholecystectomy by ultrasound
      were first studied to ensure absence of stones or biliary sludge. The women were
      then assigned to a hypocaloric regimen [5.02 MJ (1200 kcal)/d] and to receive
      1200 mg/d of ursodeoxycholic acid (UDCA), 11.3 g/d of (n-3) PUFA or a placebo for
      6 wk. BMI, CSI and NT were recorded at baseline and at the end of the
      experimental period. BMI decreased 5.75 +/- 2.7%/mo (range, 1.5-12.42%/mo) during
      the experiment. The CSI did not change in any of the groups. Cholesterol NT
      decreased significantly in the UDCA and placebo groups, but not in the (n-3) PUFA
      group. None of the women had developed gallstones at 6 wk. These results suggest
      that (n-3) PUFA maintain the CSI and NT in obese women during rapid weight loss,
      which probably results in the prevention of cholesterol gallstone formation.

PMID- 11533271
TI  - Full breast-feeding for at least four months has differential effects on growth
      before and after six months of age among children in a Mexican community.
AB  - This study examines the relationship between breast-feeding and growth from 0 to
      6 and 6 to 20 mo among 185 children in a Mexican community. Infants from a
      previous 6-mo longitudinal study were followed up for additional anthropometric
      measurements at a mean age of 19.9 mo. Size at 6 mo and at follow-up were modeled
      as outcomes of whether infants were fully breast-fed (exclusively or
      predominantly breast-fed) for at least 4 mo, controlling for size at birth and 6
      mo, respectively, and potential confounders. From birth to 6 mo, fully breast-fed
      infants had ponderal index increments of 0.07 units larger (P = 0.04) than
      comparison infants. There were no differences in weight. For length, an
      interaction between full breast-feeding and socioeconomic status (SES) was found,
      with fully breast-fed infants of low SES growing more than comparison infants,
      whereas the opposite was seen at upper SES levels. From 6 to 20 mo, fully breast
      fed infants had weight and length increments of 0.53 cm (P < 0.001) and 0.72 kg
      (P = 0.01) smaller than those of comparison infants. For ponderal index, an
      interaction between mother's education and breast-feeding revealed an inverted U
      shaped response across levels of education. Additionally, logistic regressions of
      monthly breast-feeding on lagged measurements revealed that relatively heavier
      infants had higher odds of being fully breast-fed at 2 and 3 mo. Our findings
      indicate that the benefits of full breast-feeding on growth may be most
      pronounced early in life. Further research of unmeasured confounders may explain
      the association of full breast-feeding with slower growth beyond 6 mo.

PMID- 11533272
TI  - Dietary biotin intake modulates the pool of free and protein-bound biotin in rat
      liver.
AB  - The current studies were undertaken to analyze the relationships among dietary
      biotin intake, hepatic free biotin and hepatic protein-bound biotin in rats. The
      biotin status of rats was manipulated through dietary intervention to model
      moderate biotin deficiency, adequacy, supplementation and pharmacologic biotin
      supplementation (0, 0.06, 0.6 and 100 mg/kg, respectively). Urinary biotin
      excretion was directly related to biotin intake, but no difference between biotin
      adequate and biotin-supplemented rats was detected. In contrast, plasma biotin
      was directly and significantly regulated by biotin intake at every intake level.
      A hepatic free biotin pool was directly demonstrated in these studies, and like
      plasma, its size was directly related to dietary biotin intake. The relationship
      between dietary biotin intake and protein-bound biotin was also analyzed.
      Moderate biotin deficiency markedly decreased the abundance of each biotinylated
      polypeptide in rat liver. Biotin supplementation did not significantly elevate
      the abundance of biotinylated pyruvate, propionyl CoA, methylcrotonyl CoA or
      acetyl CoA carboxylase 1. The abundance of biotinylated acetyl CoA carboxylase 2,
      however, was significantly higher in biotin-supplemented rats. Pharmacologic
      biotin intake significantly reduced the abundance of biotinylated propionyl CoA
      and methylcrotonyl CoA carboxylase. These results indicate the following: 1)
      moderate biotin deficiency reduces free and protein bound biotin; 2) biotin
      intakes in rats that mimic the currently recommended daily value (DV) do not
      result in full protein biotinylation; and 3) pharmacologic supplementation may
      reduce the abundance of functional carboxylases.

PMID- 11533273
TI  - Trans-10, cis-12, but not cis-9, trans-11, conjugated linoleic acid attenuates
      lipogenesis in primary cultures of stromal vascular cells from human adipose
      tissue.
AB  - We have previously shown that both a commercially available mixture of conjugated
      linoleic acid (CLA) isomers and the trans-10, cis-12 isomer of CLA reduced the
      triglyceride (TG) content and induced apoptosis in differentiating cultures of
      murine 3T3-L1 preadipocytes. However, the influence of CLA isomers on
      differentiating human (pre)adipocytes is unknown. Therefore, we conducted a
      series of studies using primary cultures of stromal vascular cells isolated from
      human adipose tissue to determine: 1) the influence of seeding density and
      thiazolidinedione (TZD) concentration on TG content; 2) the chronic dose response
      of cis-9, trans-11 CLA vs. trans-10, cis-12 CLA on TG content; 3) whether chronic
      linoleic acid supplementation could rescue the TG content of CLA-treated
      cultures; and 4) whether trans-10, cis-12-mediated reduction in cellular TG was
      due to decreased lipogenesis and/or increased lipolysis. In expt. 1, the TG
      content [micromol/(L x 10(6) cells)] increased as both seeding density and TZD
      concentration increased. For example, cultures seeded at 4 x 10(4) cells/cm(2)
      and supplemented with 10 micromol/L BRL 49653 had 10-fold more TG than similarly
      seeded cultures without BRL 49653. In expt. 2, TG content decreased as the level
      of trans-10, cis-12 CLA increased from 1 to 10 micromol/L, whereas the TG content
      increased with increasing concentrations of either linoleic acid or cis-9, trans
      11 CLA. In expt. 3, linoleic acid supplementation restored the TG content of
      cultures treated with trans-10, cis-12 CLA compared with cultures treated with
      CLA alone, suggesting that attenuation of TG content by CLA is reversible. In
      expt. 4, glucose incorporation into total lipid decreased with increasing levels
      of trans-10, cis-12 CLA, whereas neither CLA isomer acutely affected lipolysis.
      These data suggest that the reported antiobesity actions of a supplement
      containing a crude mixture of CLA isomers given to humans may be due to
      inhibition of lipogenesis by the trans-10, cis-12 isomer.

PMID- 11533274
TI  - Dietary conjugated linoleic acids and lipid source alter fatty acid composition
      of juvenile yellow perch, Perca flavescens.
AB  - A study was conducted to examine the effects of dietary conjugated linoleic acids
      (CLA; 0, 0.5 or 1.0 g/100 g total CLA) and lipid source (menhaden oil, soybean
      oil or a 1:1 mixture of menhaden:soybean oil) on growth rates and fatty acid
      composition of yellow perch. Dietary treatments were fed to apparent satiation to
      triplicate groups of fish initially weighing 37.9 g/fish. At the end of the 9-wk
      feeding trial, no significant differences were detected in weight gain or feed
      intake among fish fed any of the dietary treatments. Dietary CLA, lipid source
      and/or their interaction significantly affected feed efficiency, total liver
      lipid concentration, and muscle and liver fatty acid concentrations. Feed
      efficiency (g gain/g feed) was significantly lower in fish fed diets containing
      soybean oil (0.51) compared with fish fed menhaden oil (0.58) or menhaden:soybean
      oil (0.60). Liver total lipid concentrations were significantly reduced in fish
      fed 0.5 and 1.0 g/100 g CLA compared with fish fed the diets containing no CLA
      and in fish fed menhaden oil compared with those fed soybean oil or a 1:1 mixture
      of menhaden:soybean oil. Total CLA levels increased in both liver and muscle as
      dietary CLA concentration increased, irrespective of lipid source. However, total
      CLA concentrations were significantly lower in liver and muscle of fish fed
      soybean oil. Total muscle CLA concentrations were 0, 1.26 and 2.92 g/100 g fatty
      acids in fish fed diets containing menhaden oil and 0, 0.5 and 1.0 g/100 g CLA,
      respectively. Mono- and polyunsaturated fatty acid (PUFA) concentrations were
      significantly lower in muscle and liver of fish fed CLA compared with fish fed
      the diets containing no CLA. In contrast, liver concentrations of saturated fatty
      acids, 14:0, 16:0 and 18:0, were significantly higher in fish fed 1.0 g/100 g
      CLA.

PMID- 11533276
TI  - In vitro starch digestion correlates well with rate and extent of starch
      digestion in broiler chickens.
AB  - Current feed evaluation systems for poultry are based on digested components
      (fat, protein and nitrogen-free extracts). Digestible starch is the most
      important energy source in broiler chicken feeds and is part of the nitrogen-free
      extract fraction. Digestible starch may be predicted using an in vitro method
      that mimics digestive processes in the gastrointestinal tract of broiler
      chickens. An experiment was designed to use this method for predicting site, rate
      and extent of starch digestion in broiler chickens. In vitro starch digestion was
      studied in 12 experimental diets differing in starch sources. These diets were
      also used in a digestibility trial with broiler chickens. Correlations between in
      vitro and in vivo starch digestion were calculated. Starch digestion after 2 h
      incubation correlated well with in vivo starch digestion in the first half of the
      small intestine (r = 0.94). A 4-h incubation period resulted in a good
      correlation between in vitro starch digestion and ileal starch digestion (r =
      0.96). In vitro starch digestion rate (h(-1)) correlated well with in vivo starch
      digestion rate (r = 0.87). In vitro starch digestion of individual starch sources
      was additive. It appeared that legume seeds and waxy corn contained two starch
      fractions, which were digested at different rates. We conclude that starch
      digestion rate in broiler chickens is well predicted by the in vitro method.

PMID- 11533275
TI  - Starch digestion rate in the small intestine of broiler chickens differs among
      feedstuffs.
AB  - Dietary starch is the major energy source for broiler chickens, and knowledge
      about its digestive behavior can be important. In a digestibility trial with 720
      broiler chickens, site, rate and extent of starch digestion were measured for 12
      feedstuffs. Starch digestion was determined using the slaughter technique, which
      involves removal of the small intestine from the recently killed chicken, with
      manual collection of the contents. Starch digestion coefficients were calculated
      from remaining starch in three segments of the small intestine and in excreta.
      Mean retention time in four segments of the small intestine was measured. This
      enabled calculations for starch digestion rate (k(d)). Ileal starch digestibility
      varied from 33% (potato starch) to 99% (tapioca). Retention time for digesta in
      the postduodenal small intestine varied from 136 min (barley diet) to 182 min
      (potato diet). On the basis of starch digestion rates, a distinction was made
      between slowly digestible starch (k(d) < 1 h(-1)), gradually digestible starch
      (k(d):1-2 h(-1)) and rapidly digestible starch (k(d) > 2 h(-1)). Starch from
      common beans was digested most slowly (k(d): 0.5 h(-1)), and starch from tapioca
      was digested most rapidly (k(d): 4.3 h(-1)). Starch digestion rates of potato
      starch and legume seeds were lower than those of cereal grains and tapioca.
      Degradation of starch entering the hind gut of the birds did not occur. Milling
      of corn affected rate, but not the extent of starch digestion. We concluded that
      site of starch digestion within the small intestine is not an accurate indicator
      for starch digestion rate.

PMID- 11533277
TI  - Selenium from selenium-rich Spirulina is less bioavailable than selenium from
      sodium selenite and selenomethionine in selenium-deficient rats.
AB  - The bioavailabilty of selenium (Se) from selenium-rich Spirulina (SeSp) was
      assessed in Se-deficient rats by measuring tissue Se accumulation and glutathione
      peroxidase (GSH-Px) activity. For 42 d, rats were subjected to dietary Se
      depletion by consumption of a Torula yeast (TY)-based diet with no Se; controls
      were fed the same diet supplemented with 75 microg Se/kg diet as sodium selenite.
      Se-deficient rats were then repleted with Se (75 microg/kg) by the addition of
      sodium selenite, selenomethionine (SeMet) or SeSp to the TY basal diet. Selenium
      speciation in SeSp emphasized the quasi-absence of selenite (2% of total Se);
      organic Se comprised SeMet (approximately 18%), with the majority present in the
      form of two selenoproteins (20-30 kDa and 80 kDa). Gross absorption of Se from
      SeSp was significantly lower than from free SeMet and sodium selenite. SeMet was
      less effective than sodium selenite in restoring Se concentration in the liver
      but not in kidney. SeSp was always much less effective. Similarly, Se from SeSp
      was less effective than the other forms of Se in restoring GSH-Px activity,
      except in plasma and red blood cells where no differences were noted among the
      three sources. This was confirmed by measuring the bioavailability of Se by slope
      ratio analysis using selenite as the reference form of Se. Although Se from SeSp
      did not replenish Se concentration and GSH-Px activity in most tissues to the
      same degree as the other forms of Se, we conclude that it is biologically useful
      and differently metabolized due to its chemical form.

PMID- 11533278
TI  - Sex hormones and the selective estrogen receptor modulator tamoxifen modulate
      weekly body weights and food intakes in adolescent and adult rats.
AB  - This study documented the effect of changes in male and female sex hormones and
      the selective estrogen receptor modulator (SERM) tamoxifen on weight gain and
      food consumption of rats from puberty to adulthood, and assessed whether age at
      onset of treatment affected outcome. In Study 1, male and female WKY rats were
      either neutered or sham-operated before puberty, and a subgroup of neutered
      females underwent estrogen replacement (ERT) at the age of puberty. In Study 2,
      subgroups of neutered females received either ERT or tamoxifen beginning well
      into the postpuberty period. Weekly body weight and food consumption were
      assessed, and food consumption was normalized to metabolic weight (body
      weight(0.67)). Neutering reduced the rate of weight gain in males (P < 0.05), but
      significantly increased it in females (P < 0.0001). ERT immediately reduced
      weight gain and prevented any further increase, resulting in weights below that
      of sham-operated females (P < 0.05). Tamoxifen prevented further weight gain and
      returned profiles to that of sham-operated females. Food consumption, normalized
      to metabolic weight, was similar in females and males, and both sexes showed a
      decrease through maturation to adulthood. Neutering decreased food consumption
      below that of sham-operated animals in both males and females (P < 0.05), and ERT
      returned it to sham levels. Despite the fact that tamoxifen had an effect on body
      weight similar to that of ERT, females receiving tamoxifen treatment consumed
      less food than both sham-operated and ERT females (P < 0.05). Weight gain is
      modulated by sex hormones in male and female rats, with both estrogen and
      tamoxifen exerting immediate effects in females, irrespective of the age at which
      treatment is initiated. Differences in food consumption do not appear to account
      for the effects of hormones and tamoxifen on body weight, suggesting that they
      exert a direct effect on overall body metabolism.

PMID- 11533279
TI  - Egg phosphatidylcholine decreases the lymphatic absorption of cholesterol in
      rats.
AB  - This study was conducted to determine the effects of phosphatidylcholine (PC)
      from different sources on intestinal absorption of cholesterol. Male Sprague
      Dawley rats were fed an AIN-93G diet containing soybean oil for 4 wk. Each rat
      with lymph cannula was infused via a duodenal catheter at 3.0 mL/h for 8 h with a
      lipid emulsion [in micromol: 451.8 triolein, 27.8 kBq 14C-cholesterol (CH), 20.7
      CH, 3.6 alpha-tocopherol, and 100 PC in 24 mL PBS, pH 6.6]. The PC in the lipid
      emulsion was egg PC (EPC), hydrogenated egg PC (HPC), or soy PC (SPC). The EPC in
      the lipid emulsion markedly lowered the lymphatic absorption of 14C-CH (24.7 +/-
      2.5% dose) compared with SPC (34.9 +/- 1.2%) and a lipid emulsion containing no
      PC (NPC) (30.8 +/- 2.0%). The HPC further lowered the absorption of 14C-CH to
      21.1 +/- 1.4% dose. The outputs of phospholipid were unaffected by the source of
      PC infused (EPC, 32.2 +/- 1.7; HPC, 31.8 +/- 1.6; and SPC, 32.9 +/- 1.8
      micromol/8 h). Compared with NPC (595.0 +/- 59.5 micromol), the total output of
      fatty acids over 8 h was increased significantly by SPC (685.4 +/- 55.8
      micromol), but decreased by HPC (467.7 +/- 28.4 micromol). The total lymphatic
      output of oleic acid (18:1), the major fatty acid infused in the form of
      triolein, did not differ among the NPC (448.0 +/- 58.2 micromol/8 h), SPC (457.9
      +/- 52.3 micromol/8 h) and EPC (412.9 +/- 20.8 micromol/8 h) groups, but was
      significantly lower in the HPC group (262.0 +/- 24.1 micromol/8 h). The findings
      provide the first evidence that EPC markedly lowers the lymphatic absorption of
      cholesterol under in vivo conditions. The inhibitory effect of EPC appears to be
      due to the higher degree of saturation of its acyl groups relative to SPC,
      suggesting that the intestinal absorption of egg cholesterol may be reduced by
      the presence of PC in egg yolk.

PMID- 11533280
TI  - Dietary (n-3) polyunsaturated fatty acids exert antihypertensive effects by
      modulating calcium signaling in T cells of rats.
AB  - After 10 wk of feeding an experimental diet enriched with (n-3) polyunsaturated
      fatty acids (PUFA), i.e., eicosapentaenoic acid [EPA, 20:5(n-3)] and [DHA, 22:6(n
      3)] (EPAX), blood pressure in spontaneously hypertensive rats (SHR), but not in
      normotensive Wistar-Kyoto (WKY) rats was reduced relative to rats fed an
      unsupplemented control diet. Concanavalin A-stimulated T-cell proliferation was
      diminished in both strains of rats fed the PUFA/EPAX diet. The experimental diet
      lowered secretion of interleukin-2 in SHR, but not in WKY rats compared with rats
      fed the control diet. To determine whether there was a defect in calcium
      homeostasis in T cells during hypertension, we employed the following agents:
      caffeine, which recruits calcium from the cytosolic Ca(2+)-induced Ca(2+)-release
      pool; ionomycin, which at low concentrations opens calcium channels; and
      thapsigargin (TG), which mobilizes [Ca(2+)]i from the endoplasmic reticulum (ER)
      pool. Caffeine-induced increases in [Ca(2+)]i were not modified by the PUFA/EPAX
      diet. The ionomycin-induced increases in [Ca(2+)]i in T cells from SHR were
      greater than in those from WKY rats; consumption of the PUFA/EPAX diet did not
      modify Ca(2+) influx in cells of either strain. The TG-induced increases in
      [Ca(2+)]i in T cells from SHR were greater than those in cells from WKY rats.
      Interestingly, consumption of the experimental diet reduced TG-evoked increases
      in [Ca(2+)]i in T cells from SHR and increased those in T cells from WKY rats,
      indicating that the PUFA/EPAX diet could reverse the calcium mobilization from
      the ER pool in T cells. These results suggest that (n-3) PUFA exert
      antihypertensive effects and modulate T-cell calcium signaling during
      hypertension in rats.

PMID- 11533281
TI  - Dietary conjugated linoleic acid modulates phenotype and effector functions of
      porcine CD8(+) lymphocytes.
AB  - In vivo vaccination and challenge studies have demonstrated that CD8(+)
      lymphocytes are essential for the development of cell-mediated protection against
      intracellular pathogens and neoplastic cells. Depletion of peripheral blood
      CD8(+) cells interferes with clearance of viruses and intracellular fungi,
      induction of delayed type hypersensitivity responses and antitumoral activity. In
      contrast to humans or mice, porcine peripheral CD8(+) lymphocytes are
      characterized by a heterogeneous expression pattern (i.e., CD8alphabeta and
      CD8alphaalpha) that facilitates the study of distinctive traits among minor
      CD8(+) cell subsets. A factorial (2 x 2) arrangement within a split-plot design,
      with 16 blocks of two littermate pigs as the experimental units for immunization
      treatment (i.e., unvaccinated or vaccinated with a proteinase-digested
      Brachyspira hyodysenteriae bacterin) and pig within block as the experimental
      unit for dietary treatment (soybean oil or conjugated linoleic acid) were used to
      investigate the phenotypic and functional regulation of CD8(+) cells by dietary
      conjugated linoleic acid (CLA). Dietary CLA supplementation induced in vivo
      expansion of porcine CD8(+) cells involving T-cell receptor
      (TCR)gammadeltaCD8alphaalpha T lymphocytes, CD3(-)CD16(+)CD8alphaalpha (a porcine
      natural killer cell subset), TCRalphabetaCD8alphabeta T lymphocytes and enhanced
      specific CD8(+)-mediated effector functions (e.g., granzyme activity). Expansion
      of peripheral blood TCRalphabetaCD8alphabeta cells was positively correlated (r =
      0.89, P < 0.01) with increased percentages of CD8alphabeta(+) thymocytes.
      Functionally, CLA enhanced the cytotoxic potential of peripheral blood
      lymphocytes and proliferation of TCRgammadeltaCD8alphaalpha cells. Collectively,
      these results indicate that dietary CLA enhances cellular immunity by modulating
      phenotype and effector functions of CD8(+) cells involved in both adaptive and
      innate immunity.

PMID- 11533282
TI  - Magnesium deficiency differentially affects the retina and visual cortex of
      intact rats.
AB  - To determine the influence of magnesium (Mg) on the visual system,
      electroretinograms (ERG) and visual evoked potentials (VEP) were recorded under
      dark-(DA) and light-adapted (LA) conditions in intact rats. Weanling rats were
      fed either a Mg-deficient (Mg-D) or a control diet for 17 d before the tests, and
      ERG, VEP and immunohistopathological analyses of retinae and cortices were made.
      In the Mg-D rats, ear congestion, hair loss and loss of body weight were
      observed, and serum Mg concentration was approximately 25% of that in the control
      rats (P < 0.01). The amplitudes of the DA a-wave and the second positive peak of
      the oscillatory potentials (OP2) of the ERG, and the negative component of the
      VEP (N1) in Mg-D rats were significantly greater than those of control rats.
      However, the amplitudes of the DA b-wave, LA 2 Hz b-wave, the 20 Hz flicker
      responses and the implicit times of all response components did not differ
      between the two groups. The immunohistopathologic results also were not altered
      in the Mg-D rats. We suggest that the functional abnormalities induced by Mg
      deficiency may depend not only on the hyperactivity of the N-methyl-D-aspartate
      (NMDA) receptor, but also on the behavior of the Ca(2+) and Mg(2+) ions in the
      intact eye.

PMID- 11533284
TI  - Novel methodology allows simultaneous measurement of true phosphorus
      digestibility and the gastrointestinal endogenous phosphorus outputs in studies
      with pigs.
AB  - Methodology was developed for measuring the gastrointestinal endogenous
      phosphorus (P) outputs and true P digestibility values in studies with piglets.
      Four barrows, average initial body weight 6.8 kg, were fitted with a simple T
      cannula at the distal ileum and fed four diets according to a 4 x 4 Latin square
      design. Four cornstarch-based diets containing four levels of P (1.1, 2.1, 3.2
      and 4.3 g/kg diet) on a dry matter (DM) basis were formulated from soybean meal
      (SBM). Each experimental period comprised 8 d with a 4-d adaptation and 4-d
      collection of ileal digesta and feces. The apparent ileal and fecal P
      digestibility values in SBM were affected (P < 0.05) by P levels in the assay
      diets. The ileal and fecal P digestibility values increased from -24.8 to 37.1%
      and from 18.8 to 42.5%, respectively, as P contents increased from 1.1 to 4.3
      g/kg DM diet. Linear relationships (P < 0.05), expressed as g/kg DM diet intake,
      between ileal and fecal outputs and dietary inputs of P, suggested that the
      endogenous P outputs can be determined by linear regression analysis. The
      endogenous P output was higher (P < 0.05) in ileal digesta than in feces (0.86 +/
      0.09 vs. 0.31 +/- 0.06 g/kg DM diet intake). There was no difference (P > 0.05)
      between the true ileal (50.7 +/- 7.1%) and fecal (48.5 +/- 5.4%) P digestibility
      values in SBM. These results suggest that differences in P contents between assay
      diets are primarily responsible for the large variability in apparent P
      digestibility values reported within the same ingredient. Apparent digestibility
      values underestimate the true digestive utilization of P by approximately 25%.
      True rather than apparent P digestibility values should be determined and used in
      diet formulation for pigs. In addition, this study shows that the
      gastrointestinal endogenous P output is important in whole-body P requirement and
      homeostasis.

PMID- 11533283
TI  - Energy restriction reduces bone density and biomechanical properties in aged
      female rats.
AB  - Bone mineral density (BMD) is highly correlated with body weight, and weight loss
      is associated with reduced BMD. Whether such losses of BMD increase skeletal
      fragility is unclear. We examined the effect of 9 wk of energy restriction (ER)
      on bone density, mineral and matrix protein composition and biomechanical
      properties in mature (20 wk old, n = 12) and aged (48 wk old, n = 16) female
      rats. Energy-restricted rats were fed 40% less energy than controls that consumed
      food ad libitum. Bone content of mineral (ash and calcium content) and matrix
      proteins (hydroxyproline, pyridinium crosslinks and proteoglycans), serum
      hormones, site-specific bone density and biomechanical properties (peak load,
      peak torque, shear stiffness and bending stiffness) were measured at the
      conclusion of the study. In both age groups, ER reduced body weight by 15 +/- 10%
      (P < 0.001) and dramatically decreased femoral bone density by 32-35% (P < 0.01)
      compared with controls. Energy restriction resulted in a small reduction in tibia
      and humerus density, as well as biomechanical properties in the aged but not
      mature rats (P < 0.05). Reduced serum levels of insulin and estradiol due to ER
      in aged rats (P < 0.05) may play a role in altering bone quality. These data show
      that although weight loss due to ER is detrimental to some bone parameters in
      mature rats, only aged rats show consistent reductions in bone density and
      biomechanical properties.

PMID- 11533287
TI  - Nutrition and aging in developing countries.
AB  - The number of individuals aged 60 y or older is projected to double as a
      proportion of the world's population and to more than triple in number over the
      next 50 y. These changes will be most dramatic in the less developed countries,
      where the transition from a young to old age structure will be more compressed in
      time than it has been for developed countries. At the same time, there is
      evidence of a characteristic sequence of changes in diet and declines in physical
      activity associated with social and economic change. Diets are becoming higher in
      fats, animal products, and refined foods and lower in fiber, contributing to
      rapidly increasing prevalences of obesity and type 2 diabetes. The number of
      people with diabetes in developing countries is projected to almost triple by the
      year 2025. Hypertension and vascular disease are also rapidly becoming more
      prevalent. Evidence that lower birth weights are associated with greater
      likelihood of adult obesity and chronic disease underscores the magnitude of risk
      in these countries. Few programs or institutions currently exist to address the
      problems of the growing elderly population. The social changes that accompany
      urbanization will likely increase nutritional risk for this group. Despite lower
      energy intakes with age, elderly have higher requirements for several
      micronutrients, making them vulnerable to deficiencies that further aggravate
      chronic conditions. To reduce the impending burden of disease and disability
      worldwide, urgent action is needed to understand and to address the nutritional
      needs of the aging population.

PMID- 11533288
TI  - Nutrition among older adults in Africa: the situation at the beginning of the
      millenium.
AB  - Most Africans enter old age after a lifetime of poverty and deprivation, poor
      access to health care and a diet that is usually inadequate in quantity and
      quality. However, nutrition interventions in African countries are directed
      primarily toward infants and young children, as well as pregnant and lactating
      women. This situational analysis focuses on two key areas to identify priorities
      for future research and policy development: the nutritional status of older
      Africans and determinants of undernutrition. Based on the scant evidence
      available, the prevalence of undernutrition is high in older African men (9.5
      36.1%) and women (13.1-27%); however, in some urban areas there is evidence that
      older adults are experiencing the nutrition transition. Information on
      micronutrient status is sparse, yet it appears that anemia related to suboptimal
      folate status is a particular problem. Important determinants of poor nutritional
      status in the elderly in the African context include inadequate household food
      security, war and famine, and the indirect impact of HIV infection and AIDS. The
      rapidly increasing size of the older population, combined with their increased
      burden of care-giving responsibilities and severe socioeconomic hardship,
      indicates an urgent need for increased attention to this group, including applied
      research on nutrition problems and the development and evaluation of nutrition
      interventions.

PMID- 11533289
TI  - Nutrition and healthy functioning in the developing world.
AB  - There is a general lack of data for studying the relationship between nutrition
      and healthy functioning among the elderly in developing countries. Nevertheless,
      knowledge of biological relationships from studies in other countries can be
      applied to gain an understanding of what can be expected in the developing world.
      In this respect, the concept of the nutrition transition is important. However,
      nutrition transition as related to elderly populations in developing countries
      has not yet been adequately studied. The developing world is not homogeneous with
      respect to patterns of nutritional status among the elderly, and problems of both
      under- and overnutrition exist among different populations of the elderly and
      both will be important factors for future functional status levels. In addition,
      there are many extrinsic factors (such as socioeconomic, political and cultural
      factors) in these countries that are even more important in determining
      nutritional status and its relation to function. Unless research and policy
      development in developing countries escalate and keep pace with the nutrition and
      demographic transitions in these countries, high levels of disability and
      dependency are likely in the near future.

PMID- 11533290
TI  - Patterns of long-term change in body composition are associated with diet,
      activity, income and urban residence among older adults in China.
AB  - Studies describing patterns of long-term change in body composition are lacking.
      Using longitudinal data on 608 healthy, nonobese Chinese (aged 50-70 y) from the
      1993 and 1997 China Health and Nutrition Surveys, this article describes the
      prevalence, sociodemographic and lifestyle correlates of patterns of long-term
      change in midarm muscle area (MAMA) and body fat (waist circumference). All
      patterns of change (loss, maintenance [Delta < 1.3 cm(2)], or gain of MAMA with
      concurrent loss, maintenance [Delta < 2 cm(2)] or gain of body fat), were
      observed for this sample. After controlling for sex, baseline age, urban
      residence, height, weight, income, MAMA, waist circumference, smoking status,
      activity level, mean daily energy and protein intakes (from three 24-h recalls),
      and change in height, it was determined that subjects who lost both arm muscle
      and body fat were distinguished from subjects who lost arm muscle but gained body
      fat by lower income and energy intake at baseline. Although protein intakes at
      baseline did not differ between the groups that lost arm muscle, protein intakes
      were significantly higher for subjects who gained both muscle and fat. Patterns
      of change involving gains in arm muscle were associated with increased protein
      intake, urban residence, as well as moderate or heavy levels of physical activity
      at baseline. Variation in protein intake, physical activity, and urban residence
      also differentiated between the groups that gained fat. Patterns of age-related
      change in body composition appear associated with modifiable variables, including
      income, urban residence, activity and protein and energy intake.

PMID- 11533292
TI  - Glutamine Metabolism: Nutritional and Clinical Significance. Proceedings of a
      symposium. October 2000, Bermuda.

PMID- 11533291
TI  - The impact of nutritional supplementation and resistance training on the health
      functioning of free-living Chilean elders: results of 18 months of follow-up.
AB  - Body composition changes and loss of functionality in the elderly are related to
      substandard diets and progressive sedentariness. The aim of this study was to
      assess the impact of an 18-mo nutritional supplementation and resistance training
      program on health functioning of elders. Healthy elders aged > or = 70 y were
      studied. Half of the subjects received a nutritional supplement. Half of the
      supplemented and nonsupplemented subjects were randomly assigned to a resistance
      exercise training program. Every 6 mo, a full assessment was performed. A total
      of 149 subjects were considered eligible for the study and 98 (31 supplemented
      and trained, 26 supplemented, 16 trained and 25 without supplementation or
      training) completed 18 mo of follow-up. Compliance with the supplement was 48%,
      and trained subjects attended 56% of programmed sessions. Activities of daily
      living remained constant in the supplemented subjects and decreased in the other
      groups. Body weight and fat-free mass did not change. Fat mass increased from
      22.2 +/- 7.6 to 24.1 +/- 7.7 kg in all groups. Bone mineral density decreased
      less in both supplemented groups than in the nonsupplemented groups (ANOVA, P <
      0.01). Serum cholesterol remained constant in both supplemented groups and in the
      trained groups, but it increased in the control group (ANOVA, P < 0.05). Upper
      and lower limb strength, walking capacity and maximal inspiratory pressure
      increased in trained subjects. In conclusion, patients who were receiving
      nutritional supplementation and resistance training maintained functionality,
      bone mineral density and serum cholesterol levels and improved their muscle
      strength.

PMID- 11533293
TI  - Glutamine: the emperor or his clothes?
AB  - In this introduction to the Proceedings of the Symposium on Glutamine, we
      consider various lines of evidence that might potentially lead to an answer to
      the question posed in the title. We begin with a short summary of the multiple
      functions of glutamine, which are extensive and, superficially at least, equally
      as impressive as those of glutamate. However, each of these amino acids may serve
      an equivalent role in some of these functions due to their ready metabolic
      interconversion. We raise the question whether glutamine is of primordial or
      rudimentary significance or whether it is a product of somebody else's existence.
      Thus, there is a short account of the prebiotic events of evolution that led to
      the appearance of glutamine and life on Earth. In doing this, it then appears
      that glutamine is a rather schizophrenic molecule, stable and thermodynamically
      reliable in biochemical environments, but labile in chemical ones. We then turn
      to the involvement of glutamine in mammalian N (nitrogen) commerce, with initial
      emphasis on the nitrogen cycle on Earth, then N transport and N excretion, before
      assessing its contribution to carbon/energy or C/E commerce. We hypothesize that,
      in addition to its utilization in immune cell function and in normal intestinal
      tissues, glutamine is a particularly key anapleurotic and energy-yielding
      substrate in conditions of hypoxia, anoxia and dysoxia. It also serves as a
      quantitatively important gluconeogenic metabolite under normal postabsorptive
      conditions. We postulate that in certain conditions, this carbon-energy
      econometric function might be by-passed with ornithine. In conclusion, the answer
      to the question above depends on the context, and this point will receive
      elaboration in many of the individual contributions that collaborate to form
      these Proceedings.

PMID- 11533294
TI  - Amino acid regulation of gene expression.
AB  - Regulation of gene expression by amino acids is mediated through a number of
      mechanisms affecting both the transcription of DNA and the translation of mRNA.
      This report reviews recent findings demonstrating a role for amino acids in
      regulating the initiation phase of mRNA translation. The report focuses on key
      regulatory events in translation initiation and discusses some of the signaling
      pathways through which amino acid sufficiency or the lack thereof is communicated
      within the cell. It concludes with a consideration of some of the important
      unanswered questions in this rapidly advancing area of research.

PMID- 11533295
TI  - Mechanisms governing the expression of the enzymes of glutamine metabolism-
      glutaminase and glutamine synthetase.
AB  - Whether on the scale of a single cell, organ or organism, glutamine homeostasis
      is to a large extent determined by the activities of glutaminase (GA, EC 3.5.1.2)
      and glutamine synthetase (GS, EC 6.3.1.2), the two enzymes that are the focus of
      this report. GA and GS each provide examples of regulation of gene expression at
      many different levels. In the case of GA, two different genes (hepatic- and
      kidney-type GA) encode isoforms of this enzyme. The expression of hepatic GA mRNA
      is increased during starvation, diabetes and high protein diet through a
      mechanism involving increased gene transcription. In contrast, the expression of
      kidney GA mRNA is increased post-transcriptionally by a mechanism that increases
      mRNA stability during acidosis. We found recently that several isoforms of rat
      and human kidney-type GA are formed by tissue-specific alternative RNA splicing.
      Although the implications of this post-transcriptional processing mechanism for
      GA activity are not yet clear, it allows for the expression of different GA
      isoforms in different tissues and may limit the expression of GA activity in
      muscle tissues by diverting primary RNA transcripts to a spliceform that produces
      a nonfunctional translation product. The expression of GS enzyme is also
      regulated by both transcriptional and post-transcriptional mechanisms. For
      example, the GS gene is transcriptionally activated by glucocorticoid hormones in
      a tissue-specific fashion. This hormonal response allows GS mRNA levels to
      increase in selected organs during catabolic states. However, the ultimate level
      of GS enzyme expression is further governed by a post-transcriptional mechanism
      regulating GS protein stability. In a unique form of product feedback, GS protein
      turnover is increased by glutamine. This mechanism appears to provide a means to
      index the production of glutamine to its intracellular concentration and,
      therefore, to its systemic demand. Herein, we also provide experimental evidence
      that GS protein turnover is dependent upon the activity of the 26S proteosome.

PMID- 11533296
TI  - Recent molecular advances in mammalian glutamine transport.
AB  - Much has been learned about plasma membrane glutamine transporter activities in
      health and disease over the past 30 years, including their potential regulatory
      role in metabolism. Since the 1960s, discrimination among individual glutamine
      transporters was based on functional characteristics such as substrate
      specificity, ion dependence, and kinetic and regulatory properties. Within the
      past two years, several genes encoding for proteins with these defined activities
      (termed "systems") have been isolated from human and rodent cDNA libraries and
      found to be distributed among four distinct gene families. The Na(+)-dependent
      glutamine transporter genes isolated thus far are System N (SN1), System A (ATA1,
      ATA2), System ASC/B(0) (ASCT2 or ATB(0)), System B(0,+) (ATB(0,+)) and System
      y(+)L (y(+)LAT1, y(+)LAT2). Na(+)-independent glutamine transporter genes
      encoding for System L (LAT1, LAT2) and System b(0,+) (b(0,+)AT) have also been
      recently isolated, and similar to y(+)L, have been shown to function as disulfide
      linked heterodimers with the 4F2 heavy chain (CD98) or rBAT (related to b(0,+)
      amino acid transporter). In this review, the molecular features, catalytic
      mechanisms and tissue distributions of each are addressed. Although most of these
      transporters mediate the transmembrane movement of several other amino acids,
      their potential roles in regulating interorgan glutamine flux are discussed. Most
      importantly, these newly isolated transporter genes provide the long awaited
      tools necessary to study their molecular regulation during the catabolic states
      in which glutamine is considered to be "conditionally essential."

PMID- 11533298
TI  - Interaction between glutamine availability and metabolism of glycogen,
      tricarboxylic acid cycle intermediates and glutathione.
AB  - After exhaustive exercise, intravenous or oral glutamine promoted skeletal muscle
      glycogen storage. However, when glutamine was ingested with glucose polymer,
      whole-body carbohydrate storage was elevated, the most likely site being liver
      and not muscle, possibly due to increased glucosamine formation. The rate of
      tricarboxylic acid (TCA) cycle flux and hence oxidative metabolism may be limited
      by the availability of TCA intermediates. There is some evidence that
      intramuscular glutamate normally provides alpha-ketoglutarate to the
      mitochondrion. We hypothesized that glutamine might be a more efficient
      anaplerotic precursor than endogenous glutamate alone. Indeed, a greater
      expansion of the sum of muscle citrate, malate, fumarate and succinate
      concentrations was observed at the start of exercise (70% VO2(max)) after oral
      glutamine than when placebo or ornithine alpha-ketoglutarate was given. However,
      neither endurance time nor the extent of phosphocreatine depletion or lactate
      accumulation during the exercise was altered, suggesting either that TCA
      intermediates were not limiting for energy production or that the severity of
      exercise was insufficient for the limitation to be operational. We have also
      shown that in the perfused working rat heart, there is a substantial fall in
      intramuscular glutamine and alpha-ketoglutarate, especially after ischemia.
      Glutamine (but not glutamate, alpha-ketoglutarate or aspartate) was able to
      rescue the performance of the postischemic heart. This ability appears to be
      connected to the ability to sustain intracardiac ATP, phosphocreatine and
      glutathione.

PMID- 11533299
TI  - Role of mitochondrial glutaminase in rat renal glutamine metabolism.
AB  - During normal acid-base balance, the kidney extracts very little of the plasma
      glutamine. However, during metabolic acidosis, as much as one third of the plasma
      glutamine is extracted and metabolized in a single pass through this organ. The
      substantial increase in renal utilization occurs solely within the proximal
      convoluted tubule and is sustained by compensating adaptations in the intraorgan
      metabolism of glutamine. The primary pathway for renal glutamine metabolism
      involves its transport into mitochondria and its deamidation and deamination by
      glutaminase (GA) and glutamate dehydrogenase (GDH), respectively. The resulting
      ammonium ions are excreted predominantly in the urine where they function as
      expendable cations to facilitate the excretion of acids. The resulting alpha
      ketoglutarate is further metabolized to phosphoenolpyruvate and subsequently to
      glucose or CO2. The intermediate steps yield two bicarbonate ions that are
      selectively transported into the venous blood to partially compensate the
      metabolic acidosis. In rat kidney, this adaptation is sustained in part by the
      cell-specific induction of the glutaminase that results primarily from
      stabilization of the GA mRNA. The 3'-nontranslated region of the GA mRNA contains
      a direct repeat of an 8-base AU-sequence that functions as a pH-response element.
      This sequence exhibits a high affinity and specificity for zeta (z)-crystallin.
      The same protein binds to two separate, but homologous, 8-base AU-sequences
      within the 3'-nontranslated region of the GDH mRNA. The apparent binding activity
      of z-crystallin is increased significantly during onset of metabolic acidosis.
      Thus, increased binding of z-crystallin may initiate the pH-responsive
      stabilization of the two mRNAs.

PMID- 11533301
TI  - In vivo nuclear magnetic resonance studies of glutamate-gamma-aminobutyric acid
      glutamine cycling in rodent and human cortex: the central role of glutamine.
AB  - It has been recognized for many years that the metabolism of brain glutamate and
      gamma-aminobutyric acid (GABA), the major excitatory and inhibitory
      neurotransmitters, is linked to a substrate cycle between neurons and astrocytes
      involving glutamine. However, the quantitative significance of these fluxes in
      vivo was not known. Recent in vivo 13C and 15N NMR studies in rodents and 13C NMR
      in humans indicate that glutamine synthesis is substantial and that the total
      glutamate-GABA-glutamine cycling flux, necessary to replenish neurotransmitter
      glutamate and GABA, accounts for >80% of net glutamine synthesis. In studies of
      the rodent cortex, a linear relationship exists between the rate of glucose
      oxidation and total glutamate-GABA-glutamine cycling flux over a large range of
      cortical electrical activity. The molar stoichiometric relationship
      (approximately 1:1) found between these fluxes suggests that they share a common
      mechanism and that the glutamate-GABA-glutamine cycle is coupled to a major
      fraction of cortical glucose utilization. Thus, glutamine appears to play a
      central role in the normal functional energetics of the cerebral cortex.

PMID- 11533302
TI  - Glutamine and the bowel.
AB  - Since the pioneering work of Windmueller and Spaeth, the importance of glutamine
      to the support of intestinal mucosal metabolic function has become generally
      accepted. Nevertheless, the mechanisms underlying this role still remain obscure.
      This paper explores a number of questions: 1) Is glutamine essential for
      intestinal function? 2) To what extent does this relate to its intermediary
      metabolism? 3) What is the importance of glutamine as a biosynthetic precursor?
      4) Is glutamine supplementation of the nutrient mixture presented to patients of
      any metabolic or clinical benefit? As a result of this exploratory exercise, the
      following general conclusions were reached: 1) Much suggestive biochemical and
      physiologic evidence exists that implies that glutamine, especially systemic
      glutamine, supports the function of the intestinal mucosal system. 2) Despite the
      extensive metabolism of this amino acid by the intestinal tissues, most evidence
      suggests that if glutamine does play a physiologic role in the bowel, it is not
      compellingly related to its intermediary metabolism. 3) There is, on the other
      hand, evidence that the mucosal cells not only utilize extracellular glutamine
      but synthesize the amino acid. Given that inhibition of glutamine synthesis
      inhibits both proliferation and differentiation of mucosal cell cultures, this
      suggests some more subtle regulatory role. This notion is supported by the
      demonstration that glutamine will activate a number of genes associated with cell
      cycle progression in the mucosa. 4) Despite the accumulated evidence, the
      mechanisms underlying glutamine's function and the question whether glutamine
      supplementation uniformly benefits mucosal health remain equivocal at best.

PMID- 11533303
TI  - Glutamine and cell signaling in liver.
AB  - In the liver, glutamine plays an important role in ammonia detoxication and the
      regulation of pH homeostasis ("intercellular glutamine cycle"). In addition, this
      amino acid regulates liver metabolism and transport by mechanisms that cannot be
      attributed to its metabolism. Examples include the stimulation of protein and
      glycogen synthesis and bile acid secretion and the inhibition of proteolysis in
      liver. The major trigger for such effects is an increased hepatocyte hydration
      due to the cumulative uptake of glutamine into the cells, which activates
      osmosignaling pathways involving mitogen-activated protein kinases (MAPK).
      Glutamine- and hypoosmolarity-induced cell swelling activates extracellular
      signal-regulated kinases (ERK) and p38(MAPK). Activation of these MAPK results in
      an increased capacity of bile acid excretion into bile due to a rapid
      translocation of canalicular transport ATPases from a subcanalicular storage
      compartment to the canalicular membrane. Similarly, glutamine augments biliary
      excretion of cysteinyl leukotrienes in endotoxin-treated rat livers. Also, the
      antiproteolytic effect of glutamine is largely due to glutamine-induced cell
      swelling, which activates osmosignaling pathways. Here, the glutamine-induced
      p38(MAPK) activation mediates the inhibition of autophagic proteolysis at the
      level of autophagosome formation.

PMID- 11533304
TI  - Why is L-glutamine metabolism important to cells of the immune system in health,
      postinjury, surgery or infection?
AB  - Glutamine is normally considered to be a nonessential amino acid. However, recent
      studies have provided evidence that glutamine may become "conditionally
      essential" during inflammatory conditions such as infection and injury. It is now
      well documented that under appropriate conditions, glutamine is essential for
      cell proliferation, that it can act as a respiratory fuel and that it can enhance
      the function of stimulated immune cells. Studies thus far have determined the
      effect of extracellular glutamine concentration on lymphocyte proliferation and
      cytokine production, macrophage phagocytic plus secretory activities and
      neutrophil bacterial killing. Other cells of the immune system remain to be
      studied. The high rate of glutamine utilization and its importance to the
      function of lymphocytes, macrophages and neutrophils have raised the question
      "why glutamine?" because these cells have access to a variety of metabolic fuels
      both in vivo and in vitro. I have attempted to answer this question in this
      article. Additionally, knowledge of the rate of utilization and the pathway of
      metabolism of glutamine by cells of the immune system raises some intriguing
      questions concerning therapeutic manipulation of utilization of this amino acid
      such that the proliferative, phagocytic and secretory capacities of cells of the
      defense system may be beneficially altered. Evidence to support the hypothesis
      that glutamine is beneficially immunomodulatory in animal models of infection and
      trauma, as well as trauma in humans, is provided.

PMID- 11533306
TI  - Glutamine in animal science and production.
AB  - With its many proposed metabolic roles, glutamine would seem to have major
      potential in normal animal production systems as well as during situations
      involving adverse challenges. In practice, however, responses to glutamine
      supplementation have been inconsistent. Thus, during lactation and growth studies
      in ruminants, both positive and null effects on production responses have been
      reported. Similarly, therapeutic responses to glutamine supplementation during
      various digestive tract disorders have been inconsistent in both pigs and
      ruminants. This is despite a proven involvement in the nucleic acid biosynthesis
      necessary to support cell proliferation. In sheep, at least, glutamine may exert
      a protective effect against hepatic amino acid (AA) oxidation, particularly for
      methionine. This may offer anabolic potential because methionine is the first
      limiting AA in a number of animal feedstuffs. Glutamine is also important in
      control of metabolic acidosis, but, in contrast to rodents, the main site of
      production seems to be extra-hepatic. In the immune system, while lymphocyte
      proliferation is glutamine-dependent, intracellular concentrations are low (in
      contrast to other tissues, such as muscle and liver). Instead, glutamate is
      accumulated, but the majority of this (approximately 65%) is derived in vivo from
      plasma glutamine. In sheep, endotoxin challenge elevates the plasma flux of
      glutamine, with a corresponding decrease in plasma concentration. At the same
      time, both the glutamate accumulation and fractional rate of protein synthesis
      within lymphocytes are enhanced. These lymphocyte responses, however, are not
      altered by an AA supplement that contains glutamine. Overall, although glutamine
      obviously plays important metabolic roles within the body, supplementation does
      not appear to provide consistent beneficial or therapeutic effects, except during
      certain catabolic situations. Glutamine availability, therefore, does not seem to
      be a limitation in many challenge situations. Rather, glutamine may signal
      alterations in nutrient demands among organs and a better understanding of this
      role may increase understanding of where modulation of glutamine status would be
      beneficial.

PMID- 11533308
TI  - Glutamine metabolism in sepsis and infection.
AB  - Severe infection causes marked derangements in the flow of glutamine among
      organs, and these changes are accompanied by significant alterations in regional
      cell membrane transport and intracellular glutamine metabolism. Skeletal muscle,
      the major repository of glutamine, exhibits a twofold increase in glutamine
      release during infection, which is associated with a significant increase in
      endogenous glutamine biosynthesis. Despite an increase in glutamine synthetase
      activity in skeletal muscle, the intracellular glutamine pool becomes depleted,
      indicating that release rates exceed rates of synthesis. Simultaneously, the
      circulating pool of glutamine does not increase, indicating accelerated uptake by
      other organs. The liver appears to be the major organ of glutamine uptake in
      severe infection; studies in endotoxemic rodents have shown net hepatic glutamine
      uptake to increase by as much as 8- to 10-fold. This increase is due partially to
      increases in liver blood flow, but also to a three- to fourfold increase in
      hepatocyte System N activity in the liver. Cytokines and glucocorticoids mediate
      the increased uptake of glutamine by the liver in septic states as well as other
      compounds. Sepsis does not appear to induce an increase in System N gene
      expression, indicating that the increase in hepatic glutamine transport observed
      during severe infection is probably regulated at the protein level. The bowel
      displays a decrease in glutamine utilization during sepsis, a response that may
      be related to the decrease in circulating insulin-like growth factor-1 (IGF-1)
      levels that is characteristic of sepsis. Recent studies suggest that IGF-1 has a
      direct effect on stimulating glutamine transport across the gut lumen and thus
      may represent a therapeutic avenue for improving gut nutrition during severe
      infection. The cells of the immune system (lymphocytes, macrophages) are also
      major glutamine consumers during inflammatory states in which cell proliferation
      is increased. Under these conditions, glutamine availability can become rate
      limiting for key cell functions, such as phagocytosis and antibody production.

PMID- 11533309
TI  - Glutamine and cancer.
AB  - Glutamine is the most abundant free amino acid in the human body; it is essential
      for the growth of normal and neoplastic cells and for the culture of many cell
      types. Cancer has been described as a nitrogen trap. The presence of a tumor
      produces great changes in host glutamine metabolism in such a way that host
      nitrogen metabolism is accommodated to the tumor-enhanced requirements of
      glutamine. To be used, glutamine must be transported into tumor mitochondria.
      Thus, an overview of the role of glutamine in cancer requires not only a
      discussion of host and tumor glutamine metabolism, but also its circulation and
      transport. Because glutamine depletion has adverse effects for the host, the
      effect of glutamine supplementation in the tumor-bearing state should also be
      studied. This communication reviews the state of knowledge of glutamine and
      cancer, including potential therapeutic implications.

PMID- 11533310
TI  - The effect of glutamine supplementation in patients following elective surgery
      and accidental injury.
AB  - The metabolic response to injury, whether a controlled elective surgical
      procedure or an accidental injury, is characterized by the breakdown of skeletal
      muscle protein and the translocation of the amino acids to visceral organs and
      the wound. At these sites, the substrate serves to enhance host defenses, and
      support vital organ function and wound repair. Glutamine (GLN) plays a major role
      in these processes, accounting for approximately one third of the translocated
      nitrogen. From available data, GLN-supplemented intravenous nutrition in patients
      undergoing elective surgery improves nitrogen balance, helps correct the
      decreased GLN concentration found in the free intracellular skeletal muscle amino
      acid pool and enhances net protein synthesis (particularly in skeletal muscle).
      Six randomized blind trials (two multicentered investigations) reported a
      decreased length in hospital stay in postoperative patients receiving GLN
      supplementation. After blunt trauma, GLN supplementation increased plasma
      concentrations, attenuated the immunosuppression commonly observed and decreased
      the rate of infection. Patients with burn injury have low GLN plasma and
      intramuscular concentrations; turnover and synthesis rate are accelerated, yet
      apparently inadequate to support normal concentrations. These data suggest that
      GLN supplementation has important effects in catabolic surgical patients, but the
      exact mechanisms to explain these events remain unknown, and more research is
      required to explain the apparent benefits of dietary GLN.

PMID- 11533312
TI  - Industrial production of L-glutamine.
AB  - The industrial production of L-glutamine (L-Gln) started with its fermentation in
      the late 1960s. Currently, it is manufactured for use as pharmaceuticals and
      health foods at the worldwide annual production of approximately 2000 metric
      tons. To manufacture high quality L-Gln at a low cost, it is of prime importance
      to obtain a strain of microorganism with good production efficiency and minimum
      by-products. Furthermore, to obtain the final crystalline powder product, the
      efficient removal of impurities contained in the fermentation broth becomes
      paramount. Therefore, the industrial process is designed to take into account
      characteristics of the fermentation broth as well as chemical, physical and
      biological properties of L-Gln. Points that should be considered in the process
      design and typical industrial production of L-Gln are described in this report.

PMID- 11533313
TI  - Assessment of the safety of glutamine and other amino acids.
AB  - Glutamine is used to supplement intravenous and enteral feeding. Although there
      have been many human studies of its efficacy, there have been very few studies
      with safety as a primary goal. This article analyzes the literature on the safety
      of glutamine and also examines the available information on high intakes of total
      protein and other amino acids, so that additional indicators of potentially
      adverse effects can be suggested. Four studies that specifically addressed
      glutamine safety were identified, from which it was concluded that glutamine is
      safe in adults and in preterm infants. However, the published studies of safety
      have not fully taken account of chronic consumption by healthy subjects of all
      age groups. To help identify potential undetected hazards of glutamine intake,
      the literature on adverse effects of high dietary intake of protein and other
      amino acids was examined. High protein is reputed to cause nausea, vomiting and
      ultimately death in adults, and has been shown to result in neurological damage
      in preterm infants. Individual amino acids cause a variety of adverse effects,
      some of them potentially fatal, but neurological effects were the most frequently
      observed. Because glutamine is metabolized to glutamate and ammonia, both of
      which have neurological effects, psychological and behavioral testing may be
      especially important.

PMID- 11533314
TI  - New developments in glutamine delivery.
AB  - Numerous studies demonstrate that free glutamine can be added to commercially
      available crystalline amino acid-based preparations before their administration.
      Instability during heat sterilization and prolonged storage and limited
      solubility (35 g/L at 20 degrees C) hamper the use of free glutamine in the
      routine clinical setting. Indeed, there are many well-controlled and valuable
      trials with free glutamine, yet its use is restricted to clinical research. The
      obvious limitations of using free glutamine initiated an intensive search for
      alternative substrates. Synthetic glutamine dipeptides are stable under heat
      sterilization and highly soluble; these properties qualify the dipeptides as
      suitable constituents of nutritional preparations. Industrial production of these
      dipeptides at a reasonable price is an essential prerequisite for implications of
      dipeptide-containing solutions in clinical practice. Recent development of novel
      synthesis procedures allows increased capacity in industrial-scale production.
      Basic studies with synthetic glutamine-containing short-chain peptides provide
      convincing evidence that these new substrates are cleared rapidly from plasma
      after parenteral administration, without being accumulated in tissues and with
      negligible loss in urine. The presence of membrane-bound as well as tissue-free
      extracellular hydrolase activity facilitates a prompt and quantitative peptide
      hydrolysis, the liberated amino acids being available for protein synthesis
      and/or generation of energy. In the clinical setting, glutamine dipeptide
      nutrition beneficially influences outcome (nitrogen balance, immunity, gut
      integrity, hospital stay, morbidity and mortality). The provision of
      conditionally indispensable glutamine should be considered a necessary
      replacement of a deficiency rather than a supplementation. The beneficial effects
      observed with glutamine dipeptide nutrition should be seen simply as a correction
      of disadvantages produced by the inadequacy of conventional clinical nutrition.
      The availability of stable dipeptide preparations certainly facilitates, for the
      first time, adequate amino acid nutrition of critically ill, malnourished or
      stressed patients in the routine clinical setting and, thus, represents a new
      dimension in artificial nutrition.

PMID- 11533315
TI  - Glutamine alimentation in catabolic state.
AB  - Glutamine should be reclassified as a conditionally essential amino acid in the
      catabolic state because the body's glutamine expenditures exceed synthesis and
      low glutamine levels in plasma are associated with poor clinical outcome. After
      severe stress, several amino acids are mobilized from muscle tissue to supply
      energy and substrate to the host. Glutamine is one of the most important amino
      acids that provide this function. Glutamine acts as the preferred respiratory
      fuel for lymphocytes, hepatocytes and intestinal mucosal cells and is metabolized
      in the gut to citrulline, ammonium and other amino acids. Low concentrations of
      glutamine in plasma reflect reduced stores in muscle and this reduced
      availability of glutamine in the catabolic state seems to correlate with
      increased morbidity and mortality. Adding glutamine to the nutrition of clinical
      patients, enterally or parenterally, may reduce morbidity. Several excellent
      clinical trials have been performed to prove efficacy and feasibility of the use
      of glutamine supplementation in parenteral and enteral nutrition. The increased
      intake of glutamine has resulted in lower septic morbidity in certain critically
      ill patient populations. This review will focus on the efficacy and the
      importance of glutamine supplementation in diverse catabolic states.

PMID- 11533316
TI  - Glutamine supplementation in cancer patients receiving bone marrow
      transplantation and high dose chemotherapy.
AB  - Glutamine supplementation of enteral and parenteral nutrition support has
      received increased attention in the research community over the past decade.
      Glutamine may become a conditionally essential nutrient during certain catabolic
      states, including after bone marrow transplantation (BMT). The administration of
      enteral or parenteral glutamine seems safe and also potentially efficacious in
      some patient groups undergoing intensive treatment for cancer. Studies indicate
      that adjunctive glutamine treatment may improve nitrogen retention, decrease
      clinical infection and length of hospital stay and reduce the incidence and
      severity of mucositis after BMT and high dose chemotherapy. Although not all
      studies demonstrate benefit, there are sufficient positive data to suggest that
      this nutrient should be considered in the metabolic support of many individuals
      undergoing the catabolic process of marrow transplantation. Given the available
      data, randomized, double-blind, controlled clinical trials of glutamine-enriched
      nutrition in patients receiving BMT and high dose chemotherapy protocols are
      indicated to further define the utility of this amino acid as adjunctive therapy.
      Studies of glutamine nutrition combined with current combinations of
      cytoreductive agents and hematopoietic growth factors in BMT will be particularly
      pertinent.

PMID- 11533317
TI  - Glutamine in the fetus and critically ill low birth weight neonate: metabolism
      and mechanism of action.
AB  - Of all the amino acids, glutamine is the most versatile. Studies in the maternal
      fetal-placental unit demonstrate that both glutamine and glutamate play an
      important role in fetal and placental metabolism. If an infant is born very
      prematurely, the supply of glutamine from the mother is suddenly interrupted. The
      infant is dependent on endogenous synthesis or an exogenous supply of glutamine
      to meet the challenges of the external environment and a tripling of body weight
      in the first 3-4 mo of life. Studies of glutamine supplementation in low birth
      weight infants and critically ill adults suggest benefits, especially in terms of
      decreased nosocomial infections. Two large multicenter trials are currently
      underway that are designed to address these potential benefits in very low birth
      weight infants. These trials will not explain the mechanism of action. This
      review raises hypotheses about the role of the amide nitrogen of glutamine for
      nucleotide and glucosamine synthesis in the small intestine and how this might
      relate to greater integrity of the intestinal mucosa, hence preventing bacterial
      translocation and/or the subsequent proinflammatory response that might lead to
      multiorgan failure.

PMID- 11533319
TI  - In search of the magic nutraceutical: problems with current approaches.
AB  - Over the last few decades, substrates with immune-modulating properties have been
      identified in all groups of micro- and macronutrients. Numerous experimental
      studies have focused on evaluating these substances, either alone or in
      combination. After hundreds of experiments, no clear, consistent signal exists
      that any of these agents result in significant treatment benefits in critically
      ill patients. The current approach to establishing the efficacy of nutritional
      interventions suffers from several limitations. First, the majority of studies
      focus on surrogate or substitute end points rather than clinically important end
      points. Second, the majority of clinical studies are small, and as such are
      underpowered to detect a significant treatment effect on clinically important end
      points. Third, the methodological quality of individual randomized trials varies.
      Methodological limitations, prevalent in nutrition studies, limit the strength of
      clinical inference that can be made from study results. High quality studies have
      been shown to differ significantly from low quality studies in their estimation
      of treatment effect. Fourth, the generalizability of single-site studies is
      limited. Finally, studies sponsored solely by industry are considered to be less
      believable than studies conducted under the auspices of peer-review agencies.
      Future evaluations must be done in the context of large, multicenter, well
      designed, randomized trials focusing on clinically important end points that are
      sponsored from a variety of sources (including peer-reviewed agencies). Although
      such trials are costly, they are feasible and are much more likely to be
      believable and generalizable than the current approach.

PMID- 11533321
TI  - A community intervention trial to promote judicious antibiotic use and reduce
      penicillin-resistant Streptococcus pneumoniae carriage in children.
AB  - OBJECTIVE: Inappropriate use of antibiotics is common in primary care, and
      effective interventions are needed to promote judicious antibiotic use and reduce
      antibiotic resistance. The objective of this study was to assess the impact of
      parent and clinician education on pediatric antibiotic prescribing and carriage
      of penicillin-nonsusceptible Streptococcus pneumoniae in child care facilities.
      METHODS: A nonrandomized, controlled, community intervention trial was conducted
      in northern Wisconsin Clinicians. Clinic staff received educational materials and
      small-group presentations; materials were distributed to parents through clinics,
      child care facilities, and community organizations. Prescribing data were
      analyzed for 151 clinicians who provided primary pediatric care; nasopharyngeal
      carriage of penicillin-nonsusceptible S pneumoniae was assessed for 664 children
      in the baseline period (January-June 1997) and for 472 children in the
      postintervention period (January-June 1998). RESULTS: The median number of solid
      antibiotic prescriptions per clinician declined 19% in the intervention region
      and 8% in the control region. The median number of liquid antibiotic
      prescriptions per clinician declined 11% in the intervention region, compared
      with an increase of 12% in the control region. Retail antibiotic sales declined
      in the intervention region but not in the control region. Among participating
      children in child care facilities, there were no significant differences in
      antibiotic use or penicillin-nonsusceptible S pneumoniae colonization between the
      intervention and control regions. CONCLUSIONS: A multifaceted educational program
      for clinicians and parents led to community-wide reductions in antibiotic
      prescribing, but in child care facilities, there was no apparent impact on
      judicious antibiotic use or colonization with drug-resistant S pneumoniae. Longer
      follow-up time or greater reductions in antibiotic use may be required to
      identify changes in the pneumococcal susceptibility.

PMID- 11533322
TI  - Use of telehealth technology to extend child protection team services.
AB  - OBJECTIVE: In response to increased referrals to Florida's Child Protection Teams
      and concern regarding statewide availability of medical expertise in the area of
      child abuse and neglect, Children's Medical Services of the Florida Department of
      Health established a telemedicine project to facilitate immediate expert medical
      evaluations of alleged child abuse or neglect. This article describes a baseline
      examination of the project, including the technique of concept mapping, to
      examine how larger systematic factors influence the adaptation of telemedicine
      technology in child abuse examination settings. METHODS: This study included
      interviews of key staff plus the incorporation of concept mapping, which takes
      qualitative data (individual statements and opinions) and quantifies them (sorts
      and ranks them by order of group importance). RESULTS: Findings from interviews
      revealed that the frequency of use of telehealth services varies across the state
      as a result of several factors, including space limitations and staff training.
      Patients, however, seem to be comfortable with the use of the new technology. The
      concept mapping exercise displayed a progression of issues that are perceived to
      have an impact on the use of this technology. CONCLUSIONS: Technology use is
      affected by unforeseen variables, such as physical space limitations and
      examination room availability. Family concerns about patient privacy issues were
      rare and were resolved quickly by the health care practitioner. Although using
      this equipment is not difficult, the search for user-friendliness should be
      continued. Staff engagement early in the process likely will result in a greater
      likelihood of use of the technology.telehealth, telemedicine, child protection,
      child abuse and neglect, concept mapping.

PMID- 11533323
TI  - Impact of a waiting room videotape message on parent attitudes toward pediatric
      antibiotic use.
AB  - OBJECTIVE: To reduce the injudicious use of antibiotics, we developed an
      educational strategy that focused on parents of pediatric patients and their
      physicians. METHODS: This intervention was conducted in 5 pediatric practices in
      Arkansas during a 9-month period. Baseline data on parent attitudes about
      antibiotics and physician practice habits were measured by questionnaire. During
      the following 36 weeks, an educational videotape about the judicious use of
      antibiotics was played in waiting rooms. The videotape on antibiotics used a
      standard script based on the recommendations of the American Academy of
      Pediatrics. The physicians and staff at each site were actors in the videotape.
      During week 2 and week 36 of videotape use, parent attitudes were measured again.
      After the baseline week, the physicians and staff in each site were provided a
      standard in-service review of the American Academy of Pediatrics recommendations
      for judicious use of antibiotics. A study nurse recruited patients, administered
      questionnaires, and reviewed charts on-site. RESULTS: Parents who were exposed to
      the videotape were significantly less inclined to seek antibiotics for viral
      infections. Passively provided pamphlets were not read. No significant change in
      antibiotic prescribing by physicians was seen. CONCLUSION: Parent-focused passive
      education tools are effective at changing parent attitudes toward the use of
      antibiotics. Although physicians have blamed parent attitudes and demands for the
      overuse of antibiotics, changes in parent attitudes in this study were not
      associated with changes in prescribing rates. Changes in parent attitudes may be
      necessary but do not seem sufficient for changes in antimicrobial prescribing
      patterns.

PMID- 11533324
TI  - Randomized, controlled trial of acetazolamide and furosemide in posthemorrhagic
      ventricular dilation in infancy: follow-up at 1 year.
AB  - OBJECTIVE: Posthemorrhagic ventricular dilation (PHVD) is a complication of
      intraventricular hemorrhage in preterm infants and is associated with a high risk
      of long-term disability. Furosemide and acetazolamide are used widely in the
      treatment of PHVD in the hope of avoiding the need for placement of a
      ventriculoperitoneal shunt, but these drugs have not been evaluated in a
      controlled trial. This article reports a multicenter, randomized, controlled
      trial designed to test the hypothesis that these drugs would reduce the rate of
      shunt placement (or death) and increase survival to 1 year of age without
      disability. METHODS: Between 1992 and 1996, 177 infants who were less than 3
      months past term and had ventricular width >4 mm above the 97th centile following
      intraventricular hemorrhage were assigned randomly to either standard therapy or
      standard therapy plus drug therapy with acetazolamide (100 mg/kg/d) plus
      furosemide (1 mg/kg/d). Infants who were enrolled in the trial had a median
      gestational age of 28.6 weeks and were enrolled at a mean postnatal age of 3.6
      weeks. Forty-four percent were reported to have a cerebral parenchymal lesion on
      ultrasound scan at randomization. The primary outcome measure of death or shunt
      placement (known in all but 1 infant) occurred in 56 of 88 infants who were
      allocated to drug plus standard therapy compared with 46 of 88 who were allocated
      to standard therapy. The risk ratio was 1.23 (95% confidence interval: 0.95
      1.59). Neurodevelopmental outcome information at a corrected age of 1 year (known
      in all but 3 of 149 surviving infants) included disability or neuromotor
      impairment in 54 of 67 infants (81%) who were allocated to drug plus standard
      therapy and 52 of 69 infants (66%) who were allocated to standard therapy.
      Seventy-two of 85 infants (85%) who were allocated to drug therapy either died or
      were disabled or impaired at 1 year compared with 62 of 89 infants (70%) who were
      treated with standard therapy (risk ratio: 1.22; 95% confidence interval: 1.03
      1.4376). The excess risk of these adverse outcomes was greater among infants who
      did not have a cerebral parenchymal lesion seen on ultrasound examination at
      trial entry. CONCLUSIONS: These results suggest that the use of acetazolamide and
      furosemide in preterm infants with PHVD is ineffective in decreasing the rate of
      shunt placement and is associated with increased neurologic morbidity. This
      treatment therefore cannot be recommended.

PMID- 11533325
TI  - Prevalence of infectious diseases among internationally adopted children.
AB  - OBJECTIVE: Internationally adopted children are at increased risk of infections
      acquired in their country of origin. Ongoing surveillance of this unique
      population is needed to detect changing epidemiology and provide appropriate
      care. METHODS: We performed a retrospective cohort study of 504 children adopted
      from abroad and evaluated from 1997 to 1998 to determine the prevalence of and
      factors associated with various infectious diseases. RESULTS: The mean age of the
      study participants at medical evaluation was 1.6 years; 71% were girls, and they
      were adopted from 16 countries, including China (48%), Russia (31%), Southeast
      Asia (8%), Eastern Europe (8%), and Latin America (5%). Overall, 75 (19%) of 404
      children tested had tuberculin skin tests >/=10 mm, but all had normal chest
      radiographs. BCG vaccination (odds ratio [OR]: 7.37; 95% confidence interval
      [CI]: 3.29, 17.16) and being Russian born (OR: 2.90; 95% CI: 1.68, 5.00) were
      risk factors for latent tuberculosis infection. Fourteen (2.8%) children had
      detectable hepatitis B surface antigen, but no child had active hepatitis C,
      human immunodeficiency virus, or syphilis. Giardia lamblia antigen was detected
      in 87 (19%) of 461 tested children, and such children were older (mean: 22 months
      vs 15.5 months) and more likely to have been born in Eastern Europe (OR: 2.82;
      95% CI: 1.70, 4.68). CONCLUSIONS: We demonstrated increased rates of latent
      tuberculosis infection and G lamblia infection than previously reported. Thus,
      ongoing surveillance of internationally adopted children, international trends in
      infectious diseases, and appropriate screening will ensure the long-term health
      of adopted children as well as their families.

PMID- 11533326
TI  - Randomized, controlled trial of single versus 3-times-daily ferrous sulfate drops
      for treatment of anemia.
AB  - OBJECTIVE: Adherence to treatment of iron-deficiency anemia often is poor in both
      developed and developing countries. The current standard therapy is ferrous
      sulfate drops (or syrup) administered 3 times daily. It is possible that
      adherence would improve with a single-dose daily treatment regimen. We compared
      the use of single versus 3-times-daily ferrous sulfate drops, at the same total
      iron dose, on treatment of anemia in infants. METHODS: To obtain a large enough
      cohort of anemic subjects, we performed the study in rural Ghana. Using a
      prospective, randomized, controlled design, we studied 557 anemic children (age
      range: 6-24 months; hemoglobin values: 70-99 g/L). One group (n = 280) received
      ferrous sulfate drops once daily (40 mg elemental iron), and the control group (n
      = 277) received ferrous sulfate drops 3 times per day (total dose, 40 mg
      elemental iron). Treatment lasted for 2 months. Hemoglobin and serum ferritin
      values were measured at baseline and at the end of the study. RESULTS: Successful
      treatment of anemia (hemoglobin >100 g/L) occurred in 61% of the single-dose and
      in 56% of the 3-times-daily group. Geometric mean ferritin levels increased
      significantly in each group from baseline to the final visit. Side effects were
      minimal and similar between the 2 groups. CONCLUSION: A single versus a 3-times
      daily dose of ferrous sulfate drops over 2 months resulted in a similar rate of
      successful treatment of anemia, without side effects. To our knowledge, this is
      the first demonstration of the use of a single-dose daily regimen to treat
      anemia. Although not examined in the current study, use of a single-dose daily
      regimen may improve adherence to treatment of anemia in infants.

PMID- 11533327
TI  - Childhood outcome after early high-frequency oscillatory ventilation for neonatal
      respiratory distress syndrome.
AB  - OBJECTIVE: In a previous multicenter controlled clinical trial, we randomly
      assigned surfactant-treated premature newborns with moderate to severe
      respiratory distress syndrome to early treatment with high-frequency oscillatory
      ventilation (HFOV) or to conventional ventilation (CV). Compared with control
      infants who were treated with CV, neonates who were treated with HFOV using a
      strategy designed to recruit and maintain lung volume and minimize oxygen
      exposure had clinical evidence of improved pulmonary outcome and less lung
      injury. We report a follow-up study designed to determine whether clinical
      differences persisted between these study groups. METHODS: Patients were
      recruited from 81 survivors at 1 center (Provo, Utah) and evaluated for
      sociodemographic and health history, growth, mental development, motor
      proficiency, and pulmonary function. RESULTS: Eighty-seven percent of the cohort
      who originally were assigned to treatment with HFOV (n = 36) or CV (n = 33) were
      seen in follow-up at a mean age of 77 months (6.4 years). There were no
      differences in the frequency of hospitalization, pulmonary illness, asthma, or
      disabilities. Growth, verbal IQ, and motor development were appropriate for age
      and not different between groups. Patients who initially were randomized to
      treatment with CV showed pulmonary function evidence of decreased peak expiratory
      flow, increased residual lung volume, and maldistribution of ventilation.
      CONCLUSION: Neurodevelopmental childhood outcome after early intervention HFOV
      was normal and not different compared with patients who were treated with CV.
      Surfactant replacement combined with early HFOV using a lung recruitment strategy
      ameliorates the acute lung injury in respiratory distress syndrome that
      predisposes some preterm infants to develop chronic lung disease.

PMID- 11533329
TI  - A population-based assessment of pediatric all-terrain vehicle injuries.
AB  - OBJECTIVE: To describe the types of injuries sustained by children who ride all
      terrain vehicles (ATVs), to estimate the hospital charges associated with these
      injuries, and to determine adherence to existing rules and regulations governing
      ATV use. METHODS: Analysis of statewide hospital admissions (1992-1996) and
      emergency department (ED) visits (1996) in Utah. All patients who were younger
      than 16 years and had an external cause of injury code for ATV use were included.
      RESULTS: In 1996, 268 ED visits by children involved an ATV. Boys were twice as
      commonly injured as girls (male:female ratio: 2.1:1), and skin and orthopedic
      injuries were most frequent. The median ED charge was $368, and ED charges for
      these patients totaled $138 000. From 1992 to 1996, 130 children were
      hospitalized as a result of injuries sustained during ATV use, with median
      charges of $4240 per admission. Male to female ratio was 2.7:1, and the average
      age was 11.2 +/- 3.6 years. Mean injury severity score was 8.0 +/- 6.0, and
      median length of stay was 2 days (range: 0-43 days). Orthopedic injuries were
      most frequent, but 25% (n = 32) of children sustained head or spinal cord injury.
      Most children (94%) were discharged from the hospital, but 8 children died as a
      result of their injuries. Utah regulations prohibit children who are younger than
      8 years from driving an ATV and advise against carrying passengers on ATVs.
      However, 25% (n = 15) of all injured children who were younger than 8 were
      driving the ATV when injured, and 15% (n = 60) of injured children were
      passengers on ATVs. Four of the 8 fatally injured children were younger than 8,
      and all were driving the ATV at the time of the crash. Finally, the estimated
      injury rate per 100 registered ATVs is significantly higher for children than for
      adults (3.41 vs 1.71). CONCLUSIONS: ATV use results in significant injuries to
      children. Efforts to educate parents regarding the risks of ATV use, proper
      supervision, and use of safety equipment are warranted. Manufacturers of ATVs
      should continue to improve the safety profile of these inherently unstable
      vehicles.

PMID- 11533328
TI  - Determinants of cobalamin status in newborns.
AB  - OBJECTIVE: Cobalamin deficiency accompanied by bone marrow dysfunction and
      impaired central nervous system development has been reported in infants who were
      born to mothers with low cobalamin intake. We investigated the relation between
      cobalamin status in newborns and in their healthy mothers who consumed an
      omnivorous diet. METHODS: Serum cobalamin and the functional markers plasma
      methylmalonic acid (MMA) and total homocysteine (tHcy) were determined in 173
      newborns and their mothers. Forty-five children and mothers were reinvestigated
      after 6 weeks. RESULTS: At birth, median (interquartile range) serum cobalamin
      levels were 245 (175-323) pmol/L in the mothers and 314 (238-468) pmol/L in the
      newborns. In the neonates, serum cobalamin, but not folate, was inversely
      associated with MMA and tHcy. Among maternal factors, low serum cobalamin was the
      strongest predictor of impaired cobalamin function (defined as low cobalamin,
      high tHcy, or high MMA levels) in the newborns. After 6 weeks, the maternal
      cobalamin levels had increased (to 421 [271-502] pmol/L), whereas the newborn
      levels had declined (to 230 [158-287] pmol/L). In the same interval, the infants
      had a marked increase in plasma MMA (from 0.29 [0.24-0.38] to 0.81 [0.37-1.68]
      micromol/L). At 6 weeks, parity was a strong predictor of cobalamin status in the
      infant. CONCLUSION: The cobalamin status in the neonatal period is strongly
      associated with maternal cobalamin status and parity. A reduction in serum
      cobalamin and an increase in metabolite levels are consistent with impaired
      cobalamin function in a significant portion of the infants who were born to
      healthy, nonvegetarian mothers.

PMID- 11533330
TI  - The cause of infant and toddler subdural hemorrhage: a prospective study.
AB  - OBJECTIVE: To determine the frequency of child abuse and unintentional injury as
      a cause of infant and toddler subdural hemorrhage (SDH). METHODS: A prospective
      case series of a level I regional trauma center, regional children's hospital,
      and county medical examiner's office assessed consecutive children who were </=36
      months old and had SDH. Children who had previously known hemorrhagic disease,
      previous neurosurgical procedure, previously recognized perinatal brain injury,
      meningitis, renal dialysis, and severe dehydration were excluded. Concurrent
      medical, retinal, skeletal, and social work abuse evaluation were measured.
      Etiologic assessment using predetermined criteria was conducted. RESULTS: From
      March 1995 through December 1998, 66 children were admitted with SDH. Abuse was
      confirmed in 39 (59%), unintentional injury in 15 (23%), and indeterminate cause
      in 12 (18%). The mean age of abused children was 8.7 +/- 8.1 months and of
      children with unintentional injuries was 19.1 +/- 10.0 months. The predominant
      presenting histories for abusive injury were a minor fall or no mechanism for 33
      (84%) of 39 patients. All unintentional injuries resulted from a motor vehicle
      accident or other documented major trauma. Chronic or mixed acute and chronic SDH
      were found only in abused children (17 [44%] of 39) and in children whose
      injuries were indeterminate (8 [67%] of 12), not in children who were
      unintentionally injured (0 [0%] of 15). Long bone and/or rib fractures were found
      in 20 (51%) of 39 abused children but in only 1 unintentionally injured child.
      Retinal bleeding was present in 28 (72%) of 39 of the abused children. Only 1 of
      the 3 unintentionally injured children who had a retinal examination had
      bleeding, which was of the type associated with acute increased intracranial
      pressure. CONCLUSIONS: Nearly one fifth of infant and toddler SDH resulted from
      unintentional trauma. Of those without obvious unintentional trauma, 76% were
      corroborated to have been abused. Abused children were younger, more likely to
      have chronic SDH, and more likely to have multiple associated injuries. Their
      injury history usually was minor or absent.

PMID- 11533331
TI  - Respiratory instability of term and near-term healthy newborn infants in car
      safety seats.
AB  - OBJECTIVE: Premature infants who are discharged from intensive care nurseries are
      known to be at increased risk for apnea, bradycardia, and oxygen desaturation
      while in the upright position. These small infants also do not fit securely in
      standard infant car seats. Because of these problems, the American Academy of
      Pediatrics recommends a period of observation in a car seat for all infants who
      are born at <37 weeks' gestation. It is not clear whether this recommendation
      should apply to the minimally preterm infants (born at 35-36 weeks' gestation)
      who are healthy at birth and are hospitalized in the normal newborn nursery. The
      objective of this study was to evaluate the respiratory stability and safety
      requirements of healthy, minimally preterm infants in car seats compared with
      term infants. METHODS: Fifty healthy, nonmonitored, preterm infants (mean
      gestational age: 35.8 +/- 0.6 weeks) and 50 term infants (mean gestational age:
      39.5 +/- 1.4 weeks) were recruited from a level I newborn nursery in a community
      hospital. Appropriateness of car seat fit was documented for each infant. Heart
      rate, respiratory rate, and pulse oximetry were evaluated while infants were
      supine and in their car seats. Apneic and bradycardic events were recorded in
      addition to a continuous recording of oxygen saturation values. RESULTS: Twenty
      four percent of preterm and 4% of term newborn infants did not fit securely into
      suitable car seats despite the use of blanket rolls. Mean oxygen saturation
      values declined significantly in both preterm and term infants from 97% in the
      supine position (range: 92%-100%) to 94% after 60 minutes in their car seats
      (range: 87%-100%). Seven infants (3 preterm and 4 term) had oxygen saturation
      values of <90% for longer than 20 minutes in their car seats. Twelve percent of
      the preterm infants (95% confidence interval: 4.5%-24.3%) but no term infants had
      apneic or bradycardic events in their car seats. CONCLUSIONS: Our data support
      the current American Academy of Pediatrics recommendations that all infants who
      are born at <37 weeks' gestation, including those who are admitted to level I
      community hospitals, be observed for respiratory instability and secure fit in
      their car seats before hospital discharge. Because lowering of oxygen saturation
      values was seen uniformly in all newborn infants, car seats should be used only
      for travel, and travel should be minimized during the first months of life.

PMID- 11533332
TI  - End-of-life care for neonates and infants: the experience and effects of a
      palliative care consultation service.
AB  - OBJECTIVE: Neonates and infants have the highest death rate in the pediatric
      population, yet there is a paucity of data about their end-of-life care and
      whether a palliative care service can have an impact on that care. The objective
      of this study was to describe end-of-life care for infants, including analysis of
      palliative care consultations conducted in this population. We hypothesized that
      the palliative care consultations performed had an impact on the infants' end-of
      life care. DESIGN: A retrospective chart review using the "End of Life Chart
      Review" from the Center to Improve Care for the Dying was conducted. The
      participants were the patients at Children's Hospital of Wisconsin who died at <1
      year of age during the 4-year period between January 1, 1994, and December 31,
      1997. The patients' place of death, medical interventions performed, and
      emotionally supportive services provided to families were analyzed. RESULTS:
      Among the 196 deaths during the study period, 25 (13%) of these infants and
      families had palliative care consultations. The rate of consultations increased
      from 5% of the infant deaths in 1994 to 38% of the infant deaths in 1997. Infants
      of families that received consultations had fewer days in intensive care units,
      blood draws, central lines, feeding tubes, vasopressor and paralytic drug use,
      mechanical ventilation, cardiopulmonary resuscitation, and x-rays, and the
      families had more frequent referrals for chaplains and social services than
      families that did not have palliative care consultations. CONCLUSIONS: This study
      describes the end-of-life care that infants and their families received. Fewer
      medical procedures were performed, and more supportive services were provided to
      infants and families that had a palliative care consultation. This suggests that
      palliative care consultation may enhance end-of-life care for newborns.

PMID- 11533333
TI  - Prevalence and predictors of immunization among inner-city infants: a birth
      cohort study.
AB  - CONTEXT: Although the proportion of US children who are appropriately immunized
      increased dramatically in the past decade, rates remain suboptimal among low
      income, inner-city youth. Timely initiation of immunization is an important
      predictor of immunization status later in childhood; however, prospective studies
      identifying predictors of initiation are lacking. OBJECTIVES: The objectives of
      this study were to: 1) describe immunization patterns in a cohort of infants born
      to predominantly low-income, inner-city mothers; 2) identify determinants, as
      measured at birth, of immunization status at 3 and 7 months of age; and 3)
      identify determinants of continuation of immunization among those who initiate
      immunization by 3 months of age. DESIGN: Prospective, birth cohort study.
      METHODS: Maternal/infant dyads were systematically selected from 3 District of
      Columbia hospitals between August 1995 and September 1996. Three hundred sixty
      nine mothers were interviewed shortly after delivery, at 3 to 7 months
      postpartum, and at 7 to 12 months postpartum. Medical records were reviewed at
      all reported sites of care for 324 (88%) infants. Vaccinations assessed included
      diphtheria, tetanus, and pertussis; polio; and Haemophilus influenzae type B.
      Multivariate logistic regression analyses were used to determine factors
      associated with immunization status of infants at 3 and 7 months of age. RESULTS:
      At 3 months of age, 75% of infants were up-to-date (UTD) versus only 41% at 7
      months. In adjusted analyses, baseline factors associated with being UTD at 3
      months included enrollment in the Special Supplemental Nutrition Program for
      Women, Infants, and Children (WIC) during pregnancy, intention to breastfeed, and
      presence of the infant's grandmother in the household. Infants were less likely
      to be UTD if their mothers perceived higher barriers to immunization. Baseline
      factors associated with being UTD at 7 months included lower birth order and
      maternal employment. Among the subset of infants who were UTD at 3 months, only
      53% remained UTD at 7 months. Factors measured at the first follow-up interview
      that were associated with continuation of immunization at 7 months included
      maternal employment and lower perceived barriers. CONCLUSIONS: Immunization rates
      during the first 7 months of life were low in this inner-city population. Factors
      associated with immunization status that are potentially amenable to change
      included perceived barriers to immunization and enrollment in WIC during
      pregnancy.

PMID- 11533334
TI  - Diagnosis and treatment of feeding disorders in children with developmental
      disabilities.
AB  - OBJECTIVES: To determine the results of diagnostic evaluation and the effects of
      nutritional intervention on energy consumption, weight gain, growth, and clinical
      status of children with neurodevelopmental disabilities and suspected feeding
      disorders. METHODS: We studied 79 children with moderate to severe motor or
      cognitive dysfunction (male:female, 38:41; age, 5.8 +/- 3.7 years) who were
      referred for diagnosis and treatment of feeding or nutritional problems. Initial
      assessments included a 3-day calorie intake record, videofluoroscopic swallowing
      study (VFSS), 24-hour intraesophageal pH monitoring, milk scintigraphy, and
      esophagogastroduodenoscopy. RESULTS: These studies demonstrated gastroesophageal
      reflux (GER) with or without aspiration in 44 of 79 patients (56%), oropharyngeal
      dysphagia in 21 (27%), and aversive feeding behaviors in 14 (18%). Diagnosis
      specific approaches included medical GER therapy in 20 patients (25%),
      fundoplication plus gastrostomy tube (GT) in 18 (23%), oral supplements in 17
      (22%), feeding therapy only in 14 (18%), and GT only in 10 (13%). After 24.6 +/-
      3.0 months, relative calorie intake, expressed as intake (kcal/d)/recommended
      daily allowance (RDA, kcal/d), improved significantly (initial:final = 0.78 +/-
      0.36:1.23 +/- 0.27). The z scores increased significantly for both weight
      (initial:final = -2.80 +/- 1.33:-0.81 +/- 0.69) and height (-3.14 +/- 0.98:-2.00
      +/- 0.67). Improved subcutaneous tissue stores were demonstrated by increased
      thickness of both subscapular skinfolds (change = 71% +/- 26%) and triceps
      skinfolds (38% +/- 17%). After nutritional intervention, the acute care
      hospitalization rate, compared with the 2-year period before intervention,
      decreased from 0.4 +/- 0.18 to 0.15 +/- 0.06 admissions per patient-year and
      included only 3 admissions (0.02 per patient-year) related to feeding problems.
      CONCLUSIONS: In children with developmental disabilities, diagnosis-specific
      treatment of feeding disorders results in significantly improved energy
      consumption and nutritional status. These data also indicate that decreased
      morbidity (reflected by a lower acute care hospitalization rate) may be related,
      at least in part, to successful management of feeding problems. Our results
      emphasize the importance of a structured approach to these problems, and we
      propose a diagnostic and treatment algorithm for children with developmental
      disabilities and suspected feeding disorders.children, developmental
      disabilities, fundoplication, gastroesophageal reflux, gastrostomy,
      hospitalization, nutrition.

PMID- 11533335
TI  - Baby-friendly hospital initiative improves breastfeeding initiation rates in a US
      hospital setting.
AB  - OBJECTIVE: Breastfeeding initiation rates were compared at Boston Medical Center
      before (1995), during (1998), and after (1999) Baby-Friendly policies were in
      place. Boston Medical Center, an inner-city teaching hospital that provides care
      primarily to poor, minority, and immigrant families, achieved Baby-Friendly
      status in 1999. METHODS: Two hundred complete medical records, randomly selected
      by a computer, were reviewed from each of 3 years: 1995, 1998, and 1999. Infants
      were excluded for medical records missing feeding data, human immunodeficiency
      virus-positive parent, neonatal intensive care unit admission, maternal substance
      abuse, adoption, incarceration, or hepatitis C-positive mother. All infant
      feedings during the hospital postpartum stay were tallied, and each infant was
      categorized into 1 of 4 groups: exclusive breast milk, mostly breast milk, mostly
      formula, and exclusive formula. RESULTS: Maternal and infant demographics for all
      3 years were comparable. The breastfeeding initiation rate increased from 58%
      (1995) to 77.5% (1998) to 86.5% (1999). Infants exclusively breastfed increased
      from 5.5% (1995) to 28.5% (1998) to 33.5% (1999). Initiation rates increased
      among US-born black mothers in this population from 34% (1995) to 64% (1998) to
      74% (1999). CONCLUSIONS: Full implementation of the Ten Steps to Successful
      Breastfeeding leading to Baby-Friendly designation is an effective strategy to
      increase breastfeeding initiation rates in the US hospital setting.

PMID- 11533336
TI  - Work of breathing during constant- and variable-flow nasal continuous positive
      airway pressure in preterm neonates.
AB  - BACKGROUND: Constant-flow nasal continuous positive airway pressure (NCPAP) often
      is used in preterm neonates to recruit and maintain lung volume. Physical model
      studies indicate that a variable-flow NCPAP device provides more stable volume
      recruitment with less imposed work of breathing (WOB). Although superior lung
      recruitment with variable-flow NCPAP has been demonstrated in preterm neonates,
      corroborating WOB data are lacking. OBJECTIVE: To measure and compare WOB
      associated with the use of variable-flow versus constant-flow NCPAP in preterm
      neonates. METHODS: Twenty-four preterm infants who were receiving constant-flow
      NCPAP (means, SD) and had birth weight of 1024 +/- 253 g, gestational age of 28
      +/- 1.7 weeks, age of 14 +/- 13 days, and FIO(2) of 0.3 +/- 0.1 were studied.
      Variable-flow and constant-flow NCPAP were applied in random order. We measured
      changes in lung volume and tidal ventilation (V(T)) by DC-coupled/calibrated
      respiratory inductance plethysmography as well as esophageal pressures at NCPAP
      of 8, 6, 4, and 0 cm H(2)O. Inspiratory WOB (WOB(I)) and lung compliance were
      calculated from the esophageal pressure and V(T) data using standard methods. WOB
      was divided by V(T) to standardize the results. RESULTS: WOB(I) decreased at all
      CPAP levels with variable-flow NCPAP, with a maximal decrease at 4 cm H(2)O.
      WOB(I) increased at all CPAP levels with constant-flow CPAP. Lung compliance
      increased at all NCPAP levels with variable-flow, with a relative decrease at 8
      cm H(2)O, whereas it increased only at 8 cm H(2)O with constant-flow NCPAP.
      Compared with constant-flow NCPAP, WOB(I) was 13% to 29% lower with variable-flow
      NCPAP. CONCLUSION: WOB(I) is decreased with variable-flow NCPAP compared with
      constant-flow NCPAP. The increase in WOB(I) with constant-flow NCPAP indicates
      the presence of appreciable imposed WOB with this device. Our study, performed in
      neonates with little lung disease, indicates the possibility of lung
      overdistention at CPAP of 6 to 8 cm H(2)O with the variable-flow device. Further
      study is necessary to determine the efficacy of variable-flow NCPAP in neonates
      with significant lung disease and its use over extended periods of
      time.continuous-flow and variable-flow NCPAP, work of breathing, premature
      neonates, lung compliance.

PMID- 11533337
TI  - Matrix metalloproteinases-2, -8, and -9 and TIMP-2 in tracheal aspirates from
      preterm infants with respiratory distress.
AB  - OBJECTIVES: Matrix metalloproteinases (MMPs) are a family endoproteinases that
      act in degradation of extracellular matrix and basement membranes. The
      development of bronchopulmonary dysplasia (BPD) is characterized by early
      pulmonary inflammation, increased microvascular permeability, and subsequently by
      disordered repair. The aims of our study were to characterize the presence and
      molecular weight forms of MMP-2, -8, and -9 and their specific inhibitor, tissue
      inhibitor of metalloproteinases (TIMP)-2, in lungs of preterm infants during the
      early postnatal period and to determine whether levels of these MMPs and TIMP-2
      in tracheal aspirate fluid (TAF) are associated with acute or chronic lung
      morbidity of the preterm infant. METHODS: TAF samples were collected from 16
      intubated preterm infants (gestational age 27.0 +/- 2.0 weeks; birth weight 875
      +/- 246 g) during their first 5 postnatal days. The presence and molecular weight
      forms of MMPs and TIMP-2 were identified by Western immunoblotting, and their
      levels were evaluated by densitometric scanning. RESULTS: MMP-8 in TAF was higher
      in infants who needed treatment with surfactant (25.4 +/- 6.3 vs 10.6 +/- 1.5
      arbitrary unit/secretory component of immunoglobulin A [AU/SC]) and in whom BPD
      developed (N = 6; 27.6 +/- 5.2 vs 15.1 +/- 5.0 AU/SC). TIMP-2 levels were lower
      in infants with initial arterial to alveolar oxygen tension ratios <0.22 (2.7 +/-
      1.1 vs 16.8 +/- 7.4 AU/SC) and in infants needing mechanical ventilation for >1
      week (5.2 +/- 2.1 vs 22.8 +/- 11.7 AU/SC). CONCLUSIONS: In preterm infants, an
      imbalance between pulmonary MMP-8 and TIMP-2 participates in the acute
      inflammatory process in respiratory distress syndrome and may contribute to the
      development of chronic lung injury.

PMID- 11533338
TI  - Objective sleepiness measures in pediatric obstructive sleep apnea.
AB  - OBJECTIVES: Excessive daytime sleepiness (EDS) occurs frequently in adult
      patients with obstructive sleep apnea (OSA). However, the incidence of EDS in
      children with OSA is unknown. METHODS: To determine overall daytime sleepiness in
      pediatric OSA, 54 children with OSA, 14 children with primary snoring (PS), and
      24 controls (C) underwent an overnight diagnostic polysomnogram followed the next
      day by a multiple sleep latency test. RESULTS: The mean apnea index was 15.1 +/-
      9.5 standard deviation in OSA, 1.1 +/- 0.5 in PS, and 0.1 +/- 0.3 in C. Mean
      sleep latencies were 23.7 +/- 3.0 minutes in C, 23.7 +/- 3.1 minute in PS, and
      20.0 +/- 7.1 minute in OSA patients. However, only 7 children with OSA had mean
      sleep latencies <10 minutes. In addition, shorter sleep latencies were more
      likely to occur in more obese OSA patients and those with more severe apnea
      index, and oxyhemoglobin desaturation. CONCLUSIONS: Shortened sleep latencies
      occur in children with OSA, but EDS is infrequent and tends to develop among more
      severe and/or obese patients.

PMID- 11533339
TI  - Breath-holding spells associated with significant bradycardia: successful
      treatment with permanent pacemaker implantation.
AB  - OBJECTIVE: To determine whether children with pallid breath-holding spells
      associated with bradycardia can be treated safely and successfully with permanent
      pacemaker implantation. METHODS: The records of pediatric patients who had
      apparent breath-holding spells and associated bradycardia and were treated with
      permanent pacemaker implantation were reviewed. RESULTS: Ten pediatric patients
      with apparent breath-holding spells associated with bradycardia were treated with
      a permanent ventricular demand pacemaker at the Mayo Clinic between 1985 and
      1995. Patients had onset of symptoms between ages 6 days and 12 months and
      presented for evaluation between ages 12 months and 5 years. Duration of spells
      was 15 seconds to 10 minutes. Medications to prevent spells were unsuccessful.
      Electrocardiograms documented asystolic pauses of 1.7 to 24 seconds (mean: 11.9
      seconds). Permanent ventricular demand pacemakers were implanted at 10 months to
      5 years of age (median: 14.5 months): 9 endocardial and 1 epicardial. Three
      patients required pacemaker revision. At follow-up of 38 to 170 months (median:
      65.5), 5 patients had complete resolution of spells, 2 had only mild color change
      without loss of consciousness or seizure activity, and 3 continued to have minor
      brief spells. CONCLUSIONS: Permanent pacemaker therapy for children with pallid
      breath-holding spells associated with severe bradycardia is safe, efficacious,
      and warranted.

PMID- 11533340
TI  - Randomized trial of nutrient-enriched formula versus standard formula for
      postdischarge preterm infants.
AB  - OBJECTIVES: Preterm infants are frequently discharged from the hospital growth
      retarded and show reduced growth throughout childhood. In a large efficacy and
      safety trial, we tested the hypothesis that nutritional intervention in the first
      9 months postterm would reverse postdischarge growth deficits and improve
      neurodevelopment without adverse safety outcomes. PARTICIPANTS AND INTERVENTION:
      Two hundred eighty-four infants (mean gestation: 30.9 weeks) were studied; 229
      were randomly assigned a protein, energy, mineral, and micronutrient-enriched
      postdischarge formula (PDF; N = 113) or standard term formula (TF; N = 116) from
      discharge (mean 36.5 weeks' postmenstrual age). A reference group (N = 65) was
      breastfed until at least 6 weeks' postterm. Outcome measures. Anthropometry was
      performed at 6 weeks and 3, 6, 9, and 18 months. Development was measured at 9
      months (Knobloch, Passamanick, and Sherrard's developmental screening inventory)
      and 18 months (Bayley Scales of Infant Development II; primary outcome) postterm.
      RESULTS: At 9 months, compared with the TF group, those fed PDF were heavier
      (difference 370 g; 95% confidence interval [CI]: 84-660) and longer (difference
      1.1 cm; 95% CI: 0.3-1.9); the difference in length persisted at 18 months
      (difference 0.82 cm; 95% CI: -0.04-1.7). There was no effect on head
      circumference. The effect of diet was greatest in males; at 9 months length
      deficit with TF was 1.5cm (95% CI: 0.3-2.7), and this remained at 18 months
      (1.5cm [95% CI: 0.3-2.7]). There was no significant difference in developmental
      scores at 9 or 18 months, although PDF infants had a 2.8 (-1.3-6.8) point
      advantage in Bayley motor score scales. At 6 weeks' postterm, exclusively
      breastfed infants were already 513 g (95% CI: 310-715) lighter and 1.6cm (95% CI:
      0.8-2.3) shorter than the PDF group, and they remained smaller up to 9 months'
      postterm. CONCLUSIONS: 1) Improving postdischarge nutrition in the first 9 months
      may "reset" subsequent growth-at least until 18 months for body length. We intend
      to follow-up the children at older ages. The observed efficacy of PDF was not
      associated with adverse safety outcomes. 2) We cannot reject the hypothesis that
      postdischarge nutrition benefits motor development and this requires additional
      study. 3) Our data raise the possibility that breastfed postdischarge preterm
      infants may require nutritional supplementation, currently under investigation.

PMID- 11533341
TI  - Relationship of childhood obesity to coronary heart disease risk factors in
      adulthood: the Bogalusa Heart Study.
AB  - BACKGROUND: Childhood obesity is related to adult levels of lipids, lipoproteins,
      blood pressure, and insulin and to morbidity from coronary heart disease (CHD).
      However, the importance of the age at which obesity develops in these
      associations remains uncertain. OBJECTIVE AND DESIGN: We assessed the
      longitudinal relationship of childhood body mass index (BMI, kg/m(2)) to adult
      levels of lipids, insulin, and blood pressure among 2617 participants. All
      participants were initially examined at ages 2 to 17 years and were reexamined at
      ages 18 to 37 years; the mean follow-up was 17 years. RESULTS: Of the overweight
      children (BMI >/=95th percentile), 77% remained obese (>/=30 kg/m(2)) as adults.
      Childhood overweight was related to adverse risk factor levels among adults, but
      associations were weak (r ~ 0.1-0.3) and were attributable to the strong
      persistence of weight status between childhood and adulthood. Although obese
      adults had adverse levels of lipids, insulin, and blood pressure, levels of these
      risk factors did not vary with childhood weight status or with the age (</=8
      years, 12-17 years, or >/=18 years) of obesity onset. CONCLUSIONS: Additional
      data are needed to assess the independent relationship of childhood weight status
      to CHD morbidity. Because normal-weight children who become obese adults have
      adverse risk factor levels and probably will be at increased risk for adult
      morbidity, our results emphasize the need for both primary and secondary
      prevention.

PMID- 11533343
TI  - Increased risk for developmental disabilities in children who have major birth
      defects: a population-based study.
AB  - OBJECTIVE: We sought to quantify the strength of associations between each of
      four specific developmental disabilities (DDs) and specific types of major birth
      defects. METHODS: We linked data from 2 independent surveillance systems, the
      Metropolitan Atlanta Congenital Defects Program and the Metropolitan Atlanta
      Developmental Disabilities Surveillance Program. Children with major birth
      defects (n = 9142; born 1981-1991 in metro Atlanta) and 3- to 10-year-old
      children who were born between 1981 and 1991 in metro Atlanta and identified
      between 1991 and 1994 as having mental retardation, cerebral palsy, hearing
      impairment, or vision impairment (n = 3685) were studied. Prevalence ratio (PR),
      which is the prevalence of a DD in children with 1 or more major birth defects
      divided by the prevalence of the same DD in children without major birth defects,
      was measured. RESULTS: Among the 9142 children who were born with a major birth
      defect, 657 (7.2%) had a serious DD compared with 0.9% in children with no major
      birth defect, yielding a PR of 8.3 (95% confidence interval: 7.6-9.0). In
      general, the more severe the DD, the higher was the PR. Birth defects that
      originated in the nervous system and chromosomal defects resulted in the highest
      PRs for a subsequent DD. For all other categories of birth defects, PRs were
      lowest when all major birth defects present were confined to a single category
      (ie, isolated defects). PRs for any DD increased monotonically with the number of
      coded birth defects per child or the number of different birth defect categories
      per child, regardless of the severity of the defect or whether defects of the
      nervous system, chromosomal defects, or "other syndromes" were counted.
      CONCLUSIONS: These data highlight the possible early prenatal origins of some DDs
      and suggest that both the number of coded birth defects present and the number of
      anatomic systems involved are strongly related to functional outcomes.

PMID- 11533342
TI  - A randomized comparison of home visits and hospital-based group follow-up visits
      after early postpartum discharge.
AB  - OBJECTIVE: Short postpartum stays are common. Current guidelines provide scant
      guidance on how routine follow-up of newly discharged mother-infant pairs should
      be performed. We aimed to compare 2 short-term (within 72 hours of discharge)
      follow-up strategies for low-risk mother-infant pairs with postpartum length of
      stay (LOS) of <48 hours: home visits by a nurse and hospital-based follow-up
      anchored in group visits. METHODS: We used a randomized clinical trial design
      with intention-to-treat analysis in an integrated managed care setting that
      serves a largely middle class population. Mother-infant pairs that met LOS and
      risk criteria were randomized to the control arm (hospital-based follow-up) or to
      the intervention arm (home nurse visit). Clinical utilization and costs were
      studied using computerized databases and chart review. Breastfeeding
      continuation, maternal depressive symptoms, and maternal satisfaction were
      assessed by means of telephone interviews at 2 weeks postpartum. RESULTS: During
      a 17-month period in 1998 to 1999, we enrolled and randomized 1014 mother-infant
      pairs (506 to the control group and 508 to the intervention group). There were no
      significant differences between the study groups with respect to maternal age,
      race, education, household income, parity, previous breastfeeding experience,
      early initiation of prenatal care, or postpartum LOS. There were no differences
      with respect to neonatal LOS or Apgar scores. In the control group, 264 mother
      infant pairs had an individual visit only, 157 had a group visit only, 64 had
      both a group and an individual visit, 4 had a home health and a hospital-based
      follow-up, 13 had no follow-up within 72 hours, and 4 were lost to follow-up.
      With respect to outcomes within 2 weeks after discharge, there were no
      significant differences in newborn or maternal hospitalizations or urgent care
      visits, breastfeeding discontinuation, maternal depressive symptoms, or a
      combined clinical outcome measure indicating whether a mother-infant pair had any
      of the above outcomes. However, mothers in the home visit group were more likely
      than those in the control group to rate multiple aspects of their care as
      excellent or very good. These included the preventive advice delivered (76% vs
      59%) and the skills and abilities of the provider (84% vs 73%). Mothers in the
      home visit group also gave higher ratings on overall satisfaction with the
      newborn's posthospital care (71% vs 59%), as well as with their own posthospital
      care (63% vs 55%). The estimated cost of a postpartum home visit to the mother
      and the newborn was $265. In contrast, the cost of the hospital-based group visit
      was $22 per mother-infant pair; the cost of an individual 15-minute visit with a
      registered nurse was $52; the cost of a 15-minute individual pediatrician visit
      was $92; and the cost of a 10-minute visit with an obstetrician was $92.
      CONCLUSIONS: For low-risk mothers and newborns in an integrated managed care
      organization, home visits compared with hospital-based follow-up and group visits
      were more costly but achieved comparable clinical outcomes and were associated
      with higher maternal satisfaction. Neither strategy is associated with
      significantly greater success at increasing continuation of breastfeeding. This
      study had limited power to identify group differences in rehospitalization and
      may not be generalizable to higher-risk populations without comparable access to
      integrated hospital and outpatient care.

PMID- 11533344
TI  - Improving management of diabetic ketoacidosis in children.
AB  - OBJECTIVE: The optimal fluid management for diabetic ketoacidosis (DKA) is
      uncertain. In an effort to simplify DKA therapy, we revised the treatment
      protocol in our institution to use a simpler method of calculating fluid needs,
      use fluids with higher sodium concentration, and allow glucose concentration to
      be adjusted easily. We performed a retrospective study to determine the effects
      of these revisions. DESIGN: We compared patients treated with traditional and
      revised protocols (~220 and ~300 patients, respectively, over consecutive 2.75
      year intervals). Sixty patient records were randomly selected from the first
      group (30 treated with each of 2 protocol versions) and 30 from the second group.
      Biochemical and clinical parameters were analyzed. RESULTS: Patients selected for
      detailed analysis were similar in demographics and initial laboratory
      measurements. Patients treated under the revised fluid protocol received less
      total fluid, needed fewer intravenous fluid changes, were treated at less cost,
      and resolved acidosis more rapidly than patients treated under the original
      protocols. The rate of cerebral edema (0.3%-0.5%) was unchanged. CONCLUSION: A
      DKA protocol that necessitates less fluid delivery and fewer calculations
      simplifies therapy and is associated with more rapid correction of acidosis.

PMID- 11533345
TI  - Early postnatal dexamethasone therapy for the prevention of chronic lung disease.
AB  - OBJECTIVE: To test the hypothesis that early postnatal dexamethasone will reduce
      the incidence of death or chronic lung disease (CLD) in ventilated extremely low
      birth weight premature infants. DESIGN: Multicenter randomized double-blinded
      controlled clinical trial. SETTING: A total of 42 neonatal intensive care units
      in the Vermont Oxford Network. PARTICIPANTS: Infants weighing 501 to 1000 g were
      eligible for enrollment at 12 hours of age if they needed assisted ventilation,
      had received surfactant replacement therapy, were physiologically stable, had no
      obvious life-threatening congenital anomaly, and had blood cultures obtained and
      antibiotic therapy initiated. INTERVENTION: Infants were randomly assigned to
      dexamethasone or saline placebo. Intravenous dexamethasone was administered for
      12 days according to the following dosing schedule: 0.5 mg/kg/d for 3 days, 0.25
      mg/kg/d for 3 days, 0.10 mg/kg/d for 3 days, 0.05 mg/kg/d for 3 days. Infants in
      either group could receive treatment with selective late postnatal steroids
      beginning on day 14 of life if they were on assisted ventilation with
      supplemental oxygen greater than 30%. OUTCOME MEASUREMENTS: The primary outcome
      measure was CLD or death at 36 weeks postmenstrual age. RESULTS: The study was
      stopped before completion of sample size goals because of concern about serious
      side effects in the early steroid treatment group. A total of 542 infants were
      enrolled (early treatment N = 273, control N = 269). The 2 groups had similar
      demographic characteristics. No differences were noted in the primary outcome of
      CLD or death at 36 weeks postmenstrual age (early treatment 50% vs control: 53%,
      relative risk: 0.93; 95% confidence interval [CI]: 0.79-1.09). Fewer infants who
      received early steroid treatment had a patent ductus arteriosus (relative risk:
      0.78; 95% CI: 0.63-0.96), and fewer infants in the early steroid group received
      indomethacin therapy (relative risk: 0.74; 95% CI: 0.64-0.86) or late steroid
      treatment (relative risk: 0.69; 95% CI: 0.58-0.81). However, more infants who
      received early steroid treatment had complications associated with therapy
      including an increase in hyperglycemia (relative risk: 1.29; 95% CI: 1.13-1.46)
      and an increase in the use of insulin therapy (relative risk: 1.62; 95% CI: 1.36
      1.94). A trend toward increased gastrointestinal hemorrhage (relative risk: 1.55;
      95% CI: 0.92-2.61), gastrointestinal perforation (relative risk: 1.53; 95% CI:
      0.89-2.61), and an increased systolic blood pressure (relative risk: 1.34; 95%
      CI: 0.97-1.85) was noted. In infants receiving cranial ultrasound examinations, a
      marginal increase in periventricular leukomalacia was noted in the early steroid
      treatment group (relative risk: 2.23; 95% CI: 0.99-5.04). Infants who received
      early steroid therapy had fewer days in supplemental oxygen but experienced poor
      weight gain. CONCLUSIONS: A 12-day course of early postnatal steroid therapy
      given to extremely low birth weight infants did not decrease the risk of CLD or
      death at 36 weeks postmenstrual age and was associated with an increased risk of
      complications and poor weight gain.

PMID- 11533346
TI  - Nasal prongs continuous positive airway pressure: a simple yet powerful tool.

PMID- 11533347
TI  - Use of continuous positive airway pressure in preterm infants: comments and
      experience from New Zealand.

PMID- 11533348
TI  - Neonatal jaundice and kernicterus.

PMID- 11533349
TI  - Breath-holding spells and pacemaker implantation.

PMID- 11533350
TI  - Successful application of the baby-friendly hospital initiative contains lessons
      that must be applied to the control of formula feeding in hospitals in
      industrialized countries.

PMID- 11533351
TI  - Pulmonary edema associated with child abuse: case reports and review of the
      literature.
AB  - Pulmonary edema has been an unreported finding in the evaluation of abused
      children. We describe 2 cases of pulmonary edema in abused infants, 1 after
      confessed suffocation and the other after inflicted head injury. A review of the
      literature regarding postobstructive and neurogenic pulmonary edema suggests
      useful inferences for the forensic evaluation of maltreated children who present
      with this finding.

PMID- 11533352
TI  - Transfer of drugs and other chemicals into human milk.
AB  - The American Academy of Pediatrics places emphasis on increasing breastfeeding in
      the United States. A common reason for the cessation of breastfeeding is the use
      of medication by the nursing mother and advice by her physician to stop nursing.
      Such advice may not be warranted. This statement is intended to supply the
      pediatrician, obstetrician, and family physician with data, if known, concerning
      the excretion of drugs into human milk. Most drugs likely to be prescribed to the
      nursing mother should have no effect on milk supply or on infant well-being. This
      information is important not only to protect nursing infants from untoward
      effects of maternal medication but also to allow effective pharmacologic
      treatment of breastfeeding mothers. Nicotine, psychotropic drugs, and silicone
      implants are 3 important topics reviewed in this statement.

PMID- 11533353
TI  - Injuries associated with infant walkers.
AB  - In 1999, an estimated 8800 children younger than 15 months were treated in
      hospital emergency departments in the United States for injuries associated with
      infant walkers. Thirty-four infant walker-related deaths were reported from 1973
      through 1998. The vast majority of injuries occur from falls down stairs, and
      head injuries are common. Walkers do not help a child learn to walk; indeed, they
      can delay normal motor and mental development. The use of warning labels, public
      education, adult supervision during walker use, and stair gates have all been
      demonstrated to be insufficient strategies to prevent injuries associated with
      infant walkers. To comply with the revised voluntary standard (ASTM F977-96),
      walkers manufactured after June 30, 1997, must be wider than a 36-in doorway or
      must have a braking mechanism designed to stop the walker if 1 or more wheels
      drop off the riding surface, such as at the top of a stairway. Because data
      indicate a considerable risk of major and minor injury and even death from the
      use of infant walkers, and because there is no clear benefit from their use, the
      American Academy of Pediatrics recommends a ban on the manufacture and sale of
      mobile infant walkers. If a parent insists on using a mobile infant walker, it is
      vital that they choose a walker that meets the performance standards of ASTM F977
      96 to prevent falls down stairs. Stationary activity centers should be promoted
      as a safer alternative to mobile infant walkers.

PMID- 11533354
TI  - The assessment and management of acute pain in infants, children, and
      adolescents.
AB  - Acute pain is one of the most common adverse stimuli experienced by children,
      occurring as a result of injury, illness, and necessary medical procedures. It is
      associated with increased anxiety, avoidance, somatic symptoms, and increased
      parent distress. Despite the magnitude of effects that acute pain can have on a
      child, it is often inadequately assessed and treated. Numerous myths,
      insufficient knowledge among caregivers, and inadequate application of knowledge
      contribute to the lack of effective management. The pediatric acute pain
      experience involves the interaction of physiologic, psychologic, behavioral,
      developmental, and situational factors. Pain is an inherently subjective
      multifactorial experience and should be assessed and treated as such.
      Pediatricians are responsible for eliminating or assuaging pain and suffering in
      children when possible. To accomplish this, pediatricians need to expand their
      knowledge, use appropriate assessment tools and techniques, anticipate painful
      experiences and intervene accordingly, use a multimodal approach to pain
      management, use a multidisciplinary approach when possible, involve families, and
      advocate for the use of effective pain management in children.

PMID- 11533355
TI  - Clinical practice guideline: management of sinusitis.
AB  - This clinical practice guideline formulates recommendations for health care
      providers regarding the diagnosis, evaluation, and treatment of children, ages 1
      to 21 years, with uncomplicated acute, subacute, and recurrent acute bacterial
      sinusitis. It was developed through a comprehensive search and analysis of the
      medical literature. Expert consensus opinion was used to enhance or formulate
      recommendations where data were insufficient. A subcommittee, composed of
      pediatricians with expertise in infectious disease, allergy, epidemiology, family
      practice, and pediatric practice, supplemented with an otolaryngologist and
      radiologist, were selected to formulate the practice parameter. Several other
      groups (including members of the American College of Emergency Physicians,
      American Academy of Otolaryngology-Head and Neck Surgery, American Academy of
      Asthma, Allergy and Immunology, as well as numerous national committees and
      sections of the American Academy of Pediatrics) have reviewed and revised the
      guideline. Three specific issues were considered: 1) evidence for the efficacy of
      various antibiotics in children; 2) evidence for the efficacy of various
      ancillary, nonantibiotic regimens; and 3) the diagnostic accuracy and concordance
      of clinical symptoms, radiography (and other imaging methods), and sinus
      aspiration. It is recommended that the diagnosis of acute bacterial sinusitis be
      based on clinical criteria in children </=6 years of age who present with upper
      respiratory symptoms that are either persistent or severe. Although
      controversial, imaging studies may be necessary to confirm a diagnosis of acute
      bacterial sinusitis in children >6 years of age. Computed tomography scans of the
      paranasal sinuses should be reserved for children who present with complications
      of acute bacterial sinusitis or who have very persistent or recurrent infections
      and are not responsive to medical management. There were only 5 controlled
      randomized trials and 8 case series on antimicrobial therapy for acute bacterial
      sinusitis in children. However, these data, plus data derived from the study of
      adults with acute bacterial sinusitis, support the recommendation that acute
      bacterial sinusitis be treated with antimicrobial therapy to achieve a more rapid
      clinical cure. Children with complications or suspected complications of acute
      bacterial sinusitis should be treated promptly and aggressively with antibiotics
      and, when appropriate, drainage. Based on controversial and limited data, no
      recommendations are made about the use of prophylactic antimicrobials, ancillary
      therapies, or complementary/alternative medicine for prevention and treatment of
      acute bacterial sinusitis. This clinical practice guideline is not intended as a
      sole source of guidance in the diagnosis and management of acute bacterial
      sinusitis in children. It is designed to assist pediatricians by providing an
      analytic framework for evaluation and treatment. It is not intended to replace
      clinical judgment or establish a protocol for all patients with this condition.

PMID- 11533356
TI  - Screening examination of premature infants for retinopathy of prematurity.

PMID- 11533357
TI  - Human embryo research.
AB  - In 1996, a ban on the use of US Department of Health and Human Services funds for
      research on the creation of human embryos and research that involved the injury
      or destruction of human embryos was signed into law. This ban was partially
      reversed in 2000 when the National Institutes of Health announced it would fund
      selective research on human pluripotent stem cells. Given the potential benefits
      to society, research using human embryos is an issue that deserves additional
      consideration. The American Academy of Pediatrics believes that, under certain
      conditions, research using human embryos and pluripotent stem cells is of
      sufficient scientific importance that the National Institutes of Health should
      fund it and that federal oversight is morally preferable to the currently
      unregulated private sector approach.

PMID- 11533358
TI  - Pediatric generalists and subspecialists: determinants of career satisfaction.
AB  - OBJECTIVES: To evaluate the work life and job satisfaction of pediatric
      generalists and subspecialists in comparison to each other and to a group of
      general internists and internal medicine subspecialists. METHODS: Data were
      collected by survey of a national sample of 5704 general pediatricians,
      subspecialty pediatricians, general internists, internal medicine subspecialists,
      and family physicians who were selected randomly from the American Medical
      Association Masterfile using stratified sampling with disproportionate weighting
      to ensure ethnic diversity and representation of high managed care areas. Surveys
      were mailed up to 4 times and contained 150 items that reflected 10 facets of
      physician job satisfaction as well as an assessment of individual and practice
      demographic information. This study reports data from all groups except for
      family medicine. RESULTS: The adjusted response rate was 58% for general
      pediatricians (n = 590), 67% for specialty pediatricians (n = 345), and 52% (n =
      1823) for the entire pool. In comparison with general internists, general
      pediatricians were more likely to be female (44% vs 24%); to work part time (20%
      vs 12%); to have lower annual income ($125 679 vs $143 875); and to report
      significantly higher levels of job, career, and specialty satisfaction on a 5
      point scale (3.81 vs 3.52, 3.80 vs 3.55, and 3.76 vs 3.17 respectively). In
      comparison with internal medicine subspecialists, pediatric subspecialists were
      more likely to be female (42% vs 22%); to work in academically affiliated
      settings (35% vs 17%); to have lower incomes ($156 284 vs $192 006); to receive
      significantly less time for a complete history and physical examination (39
      minutes vs 51 minutes); and to report similar levels of job, career, and
      specialty satisfaction (3.69 vs 3.71, 3.74 vs 3.78, and 3.60 vs 3.47
      respectively). Of all 4 physician groups, general pediatricians worked the fewest
      hours (50/week), spent the greatest percentage of time in the office and the
      lowest percentage in the hospital (58% and 16%, respectively), saw the lowest
      percentage of patients with complex medical and complex psychosocial problems
      (15% and 17%, respectively), and were the least likely to endorse symptoms of
      burnout or job stress (13% and 18%, respectively). In comparison, pediatric
      subspecialists worked longer hours (59/week), spent the lowest percentage of time
      in the office and the greatest percentage of time in the hospital (22% and 44%,
      respectively), saw a much higher percentage of patients with complex medical and
      complex psychosocial problems (46% and 25%, respectively), and reported
      significantly higher levels of burnout and job stress (23% and 26%,
      respectively). CONCLUSIONS: Despite lower incomes, general pediatricians reported
      the highest levels of satisfaction and the least job stress of all 4 physician
      groups, whereas pediatric subspecialists reported levels of stress and burnout
      that raise significant concerns for the workforce of pediatric subspecialists of
      the future. Initiatives that improve clinical workload, balance inpatient and
      outpatient hours, and increase personal time of pediatric subspecialists should
      be considered.

PMID- 11533359
TI  - Improving preventive service delivery through office systems.
AB  - OBJECTIVE: Rates of childhood immunizations and other preventive services are
      lower in many practices than national goals and providers' own estimates. Office
      systems have been used in adult settings to improve the delivery of preventive
      care, but their effectiveness in pediatric practices is unknown. This study was
      designed to determine whether a group of primary care practices in 1 community
      could implement office-based quality improvement systems that would significantly
      improve their delivery of childhood preventive services. The study was part of a
      larger community-wide intervention study reported in a preceding study. METHODS:
      All the major providers of primary care to children in 1 community were recruited
      and agreed to participate (N = 8 practices). Project staff worked on-site with
      improvement teams in each practice to develop tailored systems to assess and
      improve the delivery of immunizations and screening for anemia, tuberculosis, and
      lead exposure. Office-based quality improvement systems typically involved some
      combination of chart prescreening, risk assessment forms, Post-it prompts, flow
      sheets, reminder/recall systems, and patient education materials. Office systems
      also often involved redistributing responsibilities among office staff. RESULTS:
      All 8 participating practices created improvement teams. Project staff met with
      the practices 10 to 15 times over 12 months. After the period of office
      assistance, the overall rates for all preventive services except tuberculosis
      screening increased by amounts that were both clinically and statistically
      significant. Absolute percent improvements included: complete immunizations at 12
      months, 7%; complete immunizations at 24 months, 12%; anemia screening, 30%; lead
      screening, 36%. The amount of improvement achieved varied considerably between
      practices. CONCLUSIONS: Office systems and the principles of quality improvement
      that underlie them seem to be effective in improving the delivery of childhood
      preventive services. Important predisposing factors may exist within practices
      that affect the likelihood that an individual practice will make significant
      improvements. prevention, immunizations, improvement, office systems, primary
      care.

PMID- 11533360
TI  - From concept to application: the impact of a community-wide intervention to
      improve the delivery of preventive services to children.
AB  - OBJECTIVE: To improve health outcomes of children, the US Maternal and Child
      Health Bureau has recommended more effective organization of preventive services
      within primary care practices and more coordination between practices and
      community-based agencies. However, applying these recommendations in communities
      is challenging because they require both more complex systems of care delivery
      within organizations and more complex interactions between them. To improve the
      way that preventive health care services are organized and delivered in 1
      community, we designed, implemented, and assessed the impact of a health care
      system-level approach, which involved addressing multiple care delivery
      processes, at multiple levels in the community, the practice, and the family. Our
      objective was to improve the processes of preventive services delivery to all
      children in a defined geographic community, with particular attention to health
      outcomes for low-income mothers and infants. DESIGN: Observational intervention
      study in 1 North Carolina county (population 182 000) involving low- income
      pregnant mothers and their infants, primary care practices, and departments of
      health and mental health. An interrupted time-series design was used to assess
      rates of preventive services in office practices before and after the
      intervention, and a historical cohort design was used to compare maternal and
      child health outcomes for women enrolled in an intensive home visiting program
      with women who sought prenatal care during the 9 months before the program's
      initiation. Outcomes were assessed when the infants reached 12 months of age.
      INTERVENTIONS: Our primary objective was to achieve changes in the process of
      care delivery at the level of the clinical interaction between care providers and
      patients that would lead to improved health and developmental outcomes for
      families. We selected interventions that were directed toward major risk factors
      (eg, poverty, ineffective care systems for preventive care in office practices)
      and for which there was existing evidence of efficacy. The interventions involved
      community-, practice-, and family-level strategies to improve processes of care
      delivery to families and children. The objectives of the community-level
      intervention were: 1) to achieve policy level changes that would result in
      changes in resources available at the level of clinical care, 2) to engage
      multiple practice organizations in the intervention to achieve an effect on most,
      if not all, families in the community, and 3) to enhance communication between,
      among, and within public and private practice organizations to improve
      coordination and avoid duplication of services. The objective of the practice
      level interventions was to overcome specific barriers in the process of care
      delivery so that preventive services could be effectively delivered. To assist
      the health department in implementing the family-level intervention, we provided
      assistance in hiring and training staff and ongoing consultation on staff
      supervision, including the use of structured protocols for care delivery, and
      regular feedback data about implementation of the program. Interventions with
      primary care practices focused on the design of the delivery system within the
      office and the use of teamwork and data in an "office systems" approach to
      improving clinical preventive care. All practices (N = 8) that enrolled at least
      5 infants/month received help in assessing performance and developing systems
      (eg, preventive services flow sheets) for preventive services delivery. Family
      level interventions addressed the process of care delivery to high-risk pregnant
      women (<100% poverty) and their infants. Mothers were recruited for the home
      visiting intervention when they first sought prenatal care at the community
      health center, the county's largest provider of prenatal care to underserved
      women. The home visiting intervention involved teams of nurses and educators and
      involved 2 to 4 visits per month through the infant's first year of life to
      provide parental education on fetal and infant health and development, enhance
      parents' informal support systems, and link parents with needed health and human
      services. We included training in injury prevention and discipline, and home
      visitors assisted mothers in obtaining care from one of the primary care offices.
      RESULTS: There were high levels of participation, changes in the organization of
      the delivery system, and improvements in preventive health outcomes. Agencies
      cooperated in joint contracting, staff training, and defining program
      eligibility. All 8 eligible practices agreed to participate and 7/8 implemented
      at least 1 new office system element. Of eligible women, 89% agreed to
      participate, and outcome data were available on 80% (180/225). After adjusting
      for differences in baseline characteristics, intervention group women were
      significantly more likely than comparison group women to use contraceptives (69%
      vs 47%), not smoke tobacco (27% vs 54%) and have a safe and stimulating home
      environment for their children. Intervention group children were more likely to
      have had an appropriate number of well-child care visits (57% vs 37%) and less
      likely to be injured (2% vs 7%). Intervention mothers also received Aid to
      Families with Dependent Children for fewer months after the birth of their child
      (7.7 months vs 11.3 months). CONCLUSIONS: We observed a number of positive
      effects at all 3 levels of intervention. Policy-level changes at the state and
      community led to lasting changes in the organization and financing of care, which
      enabled changes in clinical services to take place. These changes have now been
      expanded beyond this community to other communities in the state. We were also
      able to engage multiple practice organizations, reduce duplication, and improve
      the coordination of care. Changes in the process of preventive services delivery
      were noted in participating practices. Finally, the outcomes of the family-level
      intervention were comparable in direction and magnitude to the outcomes of
      previous randomized trials of the intervention. All the changes were achieved
      over a relatively brief 3-year study period, and many have been sustained since
      the project was completed. Tiered, interrelated interventions directed at an
      entire population of mothers and children hold promise to improve the
      effectiveness and outcomes of health care for families and children.

PMID- 11533361
TI  - Maternal domestic violence screening in an office-based pediatric practice.
AB  - BACKGROUND: Maternal domestic violence (MDV) screening by pediatricians is not
      well-studied. Objectives. To determine the practicality and dynamics of routine
      MDV screening in a private pediatric office and to determine the rate of MDV in
      Upper Cape Cod, Massachusetts. SETTING: A 3-pediatrician, private pediatric
      office in Falmouth, Massachusetts. PARTICIPANTS: Mothers of children aged 1 month
      to 10 years scheduled to undergo a well-child visit between February 7 and July
      7, 2000. INTERVENTION: Completion of an 11-item questionnaire related to
      violence. RESULTS: Seven hundred sixty-six families were scheduled for well
      visits. Five hundred ninety-two eligible mothers presented to the office. Five
      hundred fifty-three completed questionnaires were returned (71.2%). The rate of
      MDV was 2.5% in current relationships (95% confidence interval [CI]: 1.4-4.3),
      14.7% in past relationships (95% CI: 11.9-18.0), and 16.5% overall (95% CI: 13.5
      19.9). Increased incidence of MDV was associated with the following variables: 1)
      harm to a child (odds ratio [OR]: 57.3, 95% CI: 7.3-1232.4), 2) being in a
      relationship other than a first marriage (OR: 4.6, 95% CI: 2.7-7.8), 3) having
      been previously asked about MDV (OR: 3.5, 95% CI: 2.1-6.1), 4) having 4 or more
      children (OR: 3.1, 95% CI: 1.6-6.1), 5) Women, Infants, and Children's program
      eligibility (OR: 3.0, 95% CI: 1.8-5.0), 6) having public insurance (ie, Medicaid
      or Children's Medical Security Plan) (OR: 2.2, 95% CI: 1.3-3.7), 7) a history of
      failure to present for a scheduled well-child visit (no-show; OR: 2.0, 95% CI:
      1.0-4.2) and 8) anonymous questionnaire completion (OR: 1.7, 95% CI: 1.0-2.9).
      Thirty-two and one-half percent (32/91, 95% CI: 25.6-46.0) of mothers with a
      history of MDV recall having previously been asked about this by a health
      professional, compared with 16.9% overall (93/551, 95% CI: 13.9-20.3). Eighty-two
      and eight tenths (82.8) percent (457/552, 95% CI: 79.3-85.8) of mothers favored
      pediatricians asking about MDV. DISCUSSION: This information was gathered within
      the context of normal work hours in a busy office. No additional staff were
      required. Hence, routine MDV screening appears feasible. The results suggest that
      a documented history of child abuse in a family makes it very likely that the
      mother has also been abused. However, child abuse among abused mothers is
      probably underreported. Furthermore, because most mothers favor domestic violence
      screening, concerns about lack of acceptance of maternal screening at pediatric
      visits seem to be unfounded. Screening may actually increase satisfaction with
      care. In addition, families who do not show up for appointments are at higher
      risk. Therefore, screening only at well visits will miss an important group.
      CONCLUSIONS: Maternal domestic violence screening at well-child visits is
      practical in a private pediatric office setting. Current rates of screening are
      low; however, most mothers favor such screening. Furthermore, MDV screening
      should also be offered on a catch-up basis for those who miss well-child visits,
      as is currently recommended for immunizations.

PMID- 11533362
TI  - How much activity do youth get? A quantitative review of heart-rate measured
      activity.
AB  - OBJECTIVE: Recommendations for adult physical activity have shifted from 20 to 60
      minutes of continuous vigorous activity 3 to 5 times a week to accumulation of 30
      minutes of moderate to vigorous physical activity most days of the week.
      Variations of these guidelines also have been suggested for children, based on
      the idea of accumulating moderate to vigorous physical activity throughout the
      day, rather than attaining vigorous physical activity in continuous blocks. The
      goal of this study was to assess accumulated amounts of physical activity at
      different intensities in children. METHODS: We reviewed 26 studies (n = 1883) in
      youth aged 3 to 17 years that used heart-rate recording to measure physical
      activity in children to determine accumulated daily activity. Included were
      studies that provided time being active for at least 2 heart rate intensities at
      or above 120 beats/minute. Descriptive characteristics of the study groups were
      determined, and the influence of age, gender, and hours and days of observation
      on the slope of activity time as a function of percentage of heart rate reserve
      (HRR) was determined using hierarchical linear regression. RESULTS: Youth
      attained 128.0 +/- 45.6, 47.1 +/- 14.9, 29.3 +/- 13.7, and 14.7 +/- 6.0
      minutes/day between 20% to 40%, 40% to 50%, 50% to 60%, and greater than 60% HRR,
      respectively. Age was a significant predictor of the intercept and slope of the
      physical activity and %HRR relationship. CONCLUSION: Youth of all ages attain >60
      minutes/day of low-intensity physical activity and approximately 30 minutes/day
      of activity at traditional cardiovascular fitness training levels of 50% or more
      of HRR. Recommendations for youth activity are discussed.

PMID- 11533363
TI  - Rates of pediatric and adolescent injuries by year of age.
AB  - OBJECTIVE: The purpose of this study was to analyze causes of injury
      hospitalization/death by individual year of age and by specific causes of injury
      and to examine how well aggregate age groups represented individual year-of-age
      rates. METHODS: Hospital discharge data and death certificate data for California
      residents age 0 to 19 years with a principal external cause of injury code (E
      code) of E800 to E869, E880 to E929, or E950 to E999, calendar year 1997, were
      analyzed. Annual rates of injury hospitalization/death by year of age were
      calculated using combined hospital discharges and deaths as the numerator for
      major causes and important subcategories. For comparison, rates of injury
      hospitalization/death were calculated for conventional vital statistics age
      groups: <1 year, 1 to 4 years; 5 to 9 years, 10 to 14 years, and 15 to 19 years.
      RESULTS: In 1997 in California, 35 277 children and adolescents 0 to 19 years
      were hospitalized and 1934 died as a result of injury, a ratio of 17
      hospitalizations to 1 death. The distribution was bimodal with rates highest
      among 18-year-olds (732/100 000) and 1-year-olds (495/100 000). Except for
      children who were 5 to 9 years of age, the group rates for all injuries were not
      reflective of the individual year-of-age rates. In specific categories of
      injuries, variation in rates by year of age were masked by age group rates for
      unintentional poisoning among 1- to 4-year-olds, self-inflicted poisoning for 10-
      to 19-year-olds, falls from playground equipment among 5- to 9-year-olds, falls
      from furniture among 1- to 4-year-olds, and motor vehicle occupant injury rates
      among 10- to 19-year-olds. The peak rate of falls from playground equipment among
      6-year-olds (34/100 000) was more than twice the rate for 9-year-olds
      (15/1000,000). Motor vehicle occupant injury rates doubled between 10 and 14
      years of age and quadrupled between 14 and 18 years of age. CONCLUSIONS: Analyses
      using conventional age groups did not identify the age of highest risk for many
      causes of childhood injury. Changes in the rates often transected the traditional
      age groups and were not apparent with conventional age group analysis. These data
      can inform on the age at which to begin a specific injury intervention and on how
      to allocate resources. These data allow pediatricians and other health
      professionals to be anticipatory in providing injury prevention counseling. The
      greatest impact can be achieved by making the counseling topic most age
      appropriate in anticipation of the high-risk period.

PMID- 11533364
TI  - The association of foster care or kinship care with adolescent sexual behavior
      and first pregnancy.
AB  - OBJECTIVE: Each year more than 500 000 children enter out-of-home placement. Few
      outcome studies of these children specifically address high-risk sexual behavior
      and adolescent pregnancy. Our study investigated the relationship between living
      in kinship or foster care and high-risk reproductive behaviors in a nationally
      representative sample of women. METHODS: Data from 9620 women ages 15 to 44 years
      in the 1995 National Survey of Family Growth were analyzed in a cross-sectional
      study. Three groups-foster (n = 89), kinship (n = 513), and comparison (n = 9018)
      were identified on the basis of self-reported childhood living situations.
      Bivariate and multiple linear regression analyses were performed. The outcome
      variables were age at first sexual intercourse and at first conception and the
      number of sexual partners. RESULTS: After adjustment for multiple predictor
      variables, foster care was associated with younger age at first conception
      (difference: 11.3 months) and having greater than the median number of sexual
      partners (odds ratio: 1.7, 1.0-2.8). Kinship care was associated with younger age
      both at first intercourse (difference = 6 months) and at first conception
      (difference: 8.6 months) and having greater than the median number of sexual
      partners (odds ratio: 1.4, 1.1-1.8). There were no differences between the
      kinship and foster groups. CONCLUSIONS: A history of living in either foster or
      kinship care is a marker for high-risk sexual behaviors, and the risk is
      comparable in both out-of-home living arrangements. Recognition of these risks
      may enable health care providers to intervene with high-risk youth to prevent
      early initiation of sexual intercourse and early pregnancy.

PMID- 11533365
TI  - Family pain history predicts child health status in children with chronic
      rheumatic disease.
AB  - OBJECTIVES: To examine the relationships of parental and family pain history on
      the pain experience of children with chronic rheumatic disease. The aims of the
      study were as follows: 1) to describe the pain history of parents and families of
      children with rheumatic disease, 2) to examine relationships between parental and
      family pain history and the pain report and physician-rated health status of
      children with chronic rheumatic disease, and 3) to determine whether child coping
      mediates the relationship between family pain history and the child's pain and
      physician-rated health status. METHOD: Parents of 100 children were recruited
      from a pediatric rheumatology clinic during routine visits. Parents completed
      questionnaires assessing parental pain history and family characteristics.
      Children in the study completed a series of questionnaires to assess pain and
      pain coping strategies, including the Coping Strategies Questionnaire and parts
      of the Pediatric Pain Questionnaire. A pediatric rheumatologist provided a global
      assessment of disease severity on a 100-mm visual analog scale as an index of
      child health status. RESULTS: A high number of parents of children seen in a
      pediatric rheumatology clinic described a personal pain history. More than 90% of
      parents reported having at least 1 chronic pain condition, with an equal
      proportion reporting an episode of pain in the past month. The most commonly
      reported pain conditions were lower back pain, shoulder/neck pain, and migraine
      headache pain. On average, this group of parents reported a history of 3.5
      chronic pain conditions (standard deviation: 2.3) and reported having sought
      treatment for 1.7 (standard deviation: 2.3) of these conditions. Additionally,
      93% of all parents reported extended family members experiencing at least 1
      chronic pain condition. Correlational analyses indicated that parents reporting
      higher levels of current pain and higher mean levels of pain during the past
      month were more likely to have children reporting higher levels of current pain
      (r = 0.23 and r = 0.27). In addition, parents who sought more treatment for their
      own pain were more likely to have children reporting higher levels of pain (r =
      0.22) and presenting with poorer health status (r = 0.22). Similarly, parents
      reporting higher levels of pain-related interference with activity were more
      likely to have children reporting higher levels of current pain (r = 0.23).
      Correlational analyses also indicated that children whose extended families
      reported a history of multiple pain conditions were more likely to report higher
      levels of current pain (r = 0.24) and more pain locations (r = 0.23). Finally, a
      series of mediational statistical models confirmed that child use of the pain
      coping strategy, catastrophizing, partially accounted for the relationship
      between several parent and family pain history variables and the child's own
      current pain ratings and physician global assessment. Specifically, child
      catastrophizing mediated the relationships between the total number of treated
      pain conditions and children's current pain ratings and physician global
      assessment. In addition, child catastrophizing was shown to mediate the
      relationship between parental mean level of pain in the past month and children's
      current pain rating and the relationship between total number of family pain
      conditions and children's current pain rating. Taken together, our results
      suggest that parental and familial pain experiences predict children's use of
      catastrophizing to cope with pain, which in turn predicts physician global
      assessment and children's current pain. CONCLUSIONS: The results from the present
      study indicate that many of the parents of children seen in a pediatric
      rheumatology clinic have a personal pain history and highlight the potential
      impact of parental pain history on children's pain experiences. Specifically,
      parents who were more likely to seek treatment for their own pain or more likely
      to report interference with recreational activities because of pain had children
      with higher pain ratings and poorer health status as measured by the physician
      global assessment. Additionally, a series of mediational models showed that child
      catastrophizing serves as a specific mechanism through which parental and
      familial pain history variables influence child ratings of current pain and
      physician ratings of health status. Future studies are needed to determine
      exactly how children living in families with painful conditions become more
      reliant on catastrophizing to cope with their pain. In addition, more research is
      needed to identify other potential mediators, such as positive ways parents may
      influence children's pain coping. There are several important clinical
      implications of our findings. First, our results suggest that by gathering
      information from parents about their own pain histories, health care providers
      may be able to identify children at risk for developing maladaptive pain coping
      strategies and higher levels of disease-related pain and disability. Second, our
      results indicate that intervention programs should focus specifically on reducing
      children's use of catastrophizing to cope with their pain. Perhaps most
      importantly, our results highlight the need to include parents in interventions
      aimed at reducing children's pain and improving children's abilities to cope with
      pain.

PMID- 11533366
TI  - Montelukast, a leukotriene receptor antagonist, for the treatment of persistent
      asthma in children aged 2 to 5 years.
AB  - BACKGROUND: The greatest prevalence of asthma is in preschool children; however,
      the clinical utility of asthma therapy for this age group is limited by a narrow
      therapeutic index, long-term tolerability, and frequency and/or difficulty of
      administration. Inhaled corticosteroids and inhaled cromolyn are the most
      commonly prescribed controller therapies for young children with persistent
      asthma, although very young patients may have difficulty using inhalers, and dose
      delivery can be variable. Moreover, reduced compliance with inhaled therapy
      relative to orally administered therapy has been reported. One potential
      advantage of montelukast is the ease of administering a once-daily chewable
      tablet; additionally, no tachyphylaxis or change in the safety profile has been
      evidenced after up to 140 and 80 weeks of montelukast therapy in adults and
      pediatric patients aged 6 to 14 years, respectively. To our knowledge, this
      represents the first large, multicenter study to address the effects of a
      leukotriene receptor antagonist in children younger than 5 years of age with
      persistent asthma, as well as one of the few asthma studies that incorporated end
      points validated for use in preschool children. OBJECTIVE: Our primary objective
      was to determine the safety profile of montelukast, an oral leukotriene receptor
      antagonist, in preschool children with persistent asthma. Secondarily, the effect
      of montelukast on exploratory measures of asthma control was also studied. DESIGN
      AND STATISTICAL ANALYSIS: We conducted a double-blind, multicenter, multinational
      study at 93 centers worldwide: including 56 in the United States, and 21 in
      countries in Africa, Australia, Europe, North America, and South America. In this
      study, we randomly assigned 689 patients (aged 2-5 years) to 12 weeks of
      treatment with placebo (228 patients) or 4 mg of montelukast as a chewable tablet
      (461 patients) after a 2-week placebo baseline period. Patients had a history of
      physician-diagnosed asthma requiring use of beta-agonist and a predefined level
      of daytime asthma symptoms. Caregivers answered questions twice daily on a
      validated, asthma-specific diary card and, at specified times during the study,
      completed a validated asthma-specific quality-of-life questionnaire. Physicians
      and caregivers completed a global evaluation of asthma control at the end of the
      study. Efficacy end points included: daytime and overnight asthma symptoms, daily
      use of beta-agonist, days without asthma, frequency of asthma attacks, number of
      patients discontinued because of asthma, need for rescue medication, physician
      and caregiver global evaluations of change, asthma-specific caregiver quality of
      life, and peripheral blood eosinophil counts. Although exploratory, the efficacy
      end points were predefined and their analyses were written in a data analysis
      plan before study unblinding. At screening and at study completion, a complete
      physical examination was performed. Routine laboratory tests were drawn at
      screening and weeks 6 and 12, and submitted to a central laboratory for analysis.
      Adverse effects were collected from caregivers at each clinic visit. An intention
      to-treat approach, including all patients with a baseline measurement and at
      least 1 postrandomization measurement, was performed for all efficacy end points.
      An analysis-of-variance model with terms for treatment, study center and stratum
      (inhaled/nebulized corticosteroid use, cromolyn use, or none) was used to
      estimate treatment group means and between-group differences and to construct 95%
      confidence intervals. Treatment-by-age, -sex, -race, -radioallergosorbent test, 
      stratum, and -study center interactions were evaluated by including each term
      separately. Fisher's exact test was used for between-group comparisons of the
      frequency of asthma attacks, discontinuations from the study because of worsening
      asthma, need for rescue medication, and the frequencies of adverse effects.
      Because of an imbalance in baseline values for eosinophil counts for the 2
      treatment groups, an analysis of covariance was performed on the eosinophil
      change from baseline with the patient's baseline as covariate. STUDY
      PARTICIPANTS: Of the 689 patients enrolled, approximately 60% were boys and 60%
      were white. Patients were relatively evenly divided by age: 21%, 24%, 30%, and
      23% were aged 2, 3, 4, and 5 years, respectively. For 77% of the patients, asthma
      symptoms first developed during the first 3 years of life. During the placebo
      baseline period, patients had asthma symptoms on 6.1 days/week and used beta
      agonist on 6.0 days/week. RESULTS: In over 12 weeks of treatment of patients aged
      2 to 5 years, montelukast administered as a 4-mg chewable tablet produced
      significant improvements compared with placebo in multiple parameters of asthma
      control including: daytime asthma symptoms (cough, wheeze, trouble breathing, and
      activity limitation); overnight asthma symptoms (cough); the percentage of days
      with asthma symptoms; the percentage of days without asthma; the need for beta
      agonist or oral corticosteroids; physician global evaluations; and peripheral
      blood eosinophils. The clinical benefit of montelukast was evident within 1 day
      of starting therapy. Improvements in asthma control were consistent across age,
      sex, race, and study center, and whether or not patients had a positive
      radioallergosorbent test. Montelukast demonstrated a consistent effect regardless
      of concomitant use of inhaled/nebulized corticosteroid or cromolyn therapy.
      Caregiver global evaluations, the percentage of patients experiencing asthma
      attacks, and improvements in quality-of-life scores favored montelukast, but were
      not significantly different from placebo. There were no clinically meaningful
      differences between treatment groups in overall frequency of adverse effects or
      of individual adverse effects, with the exception of asthma, which occurred
      significantly more frequently in the placebo group. There were no significant
      differences between treatment groups in the frequency of laboratory adverse
      effects or in the frequency of elevated serum transaminase levels. Approximately
      90% of the patients completed the study. CONCLUSIONS: Oral montelukast (4-mg
      chewable tablet) administered once daily is effective therapy for asthma in
      children aged 2 to 5 years and is generally well tolerated without clinically
      important adverse effects. Similarly, in adults and children aged 6 to 14 years,
      montelukast improves multiple parameters of asthma control. Thus, this study
      confirms and extends the benefit of montelukast to younger children with
      persistent asthma.

PMID- 11533367
TI  - Fat content of the diet among preschool children in southwest Britain: II.
      relationship with growth, blood lipids, and iron status.
AB  - OBJECTIVE: In most countries, it is recommended that adults restrict fat intake
      to 30% to 35% of energy to reduce the risk of coronary heart disease and certain
      cancers. However, the appropriate level of fat in the diet of children is hotly
      debated. It has been generally accepted that fat intake by children under 2 years
      of age should not be limited because of fears that nutrient intakes and thus
      growth and iron status might be compromised. However, there is very little
      longitudinal information on the relationship between fat intake and growth in
      representative populations of free-living children under 2 years old. The
      objective of this study was to investigate the relationship between fat intake as
      a percentage of energy, and nutrient adequacy, growth, blood lipids, and iron
      status in 18- and 43-month-old children. DESIGN: This study forms part of the
      Avon Longitudinal Study of Parents and Children (ALSPAC)-a geographically-based
      cohort study in southwest England. A randomly selected subsample of the ALSPAC
      cohort attended research clinics approximately every 6 months from birth, at
      which a variety of anthropometric and other measurements were made. Dietary
      intakes at 18 and 43 months were assessed using a 3-day unweighed food record. A
      capillary blood sample was taken at 18 months for measurement of hemoglobin and
      ferritin levels. Nonfasting venous blood samples were taken at 31 and 43 months
      and analyzed for total and high-density lipoprotein cholesterol. The children
      were divided into quartiles of fat intake as a percentage of energy (QFI). QFI
      groups were compared for the number of children reaching recommended nutrient
      intakes, and for anthropometry, measures of iron status, and blood lipid levels.
      PARTICIPANTS: Nine hundred fifty-one children at 18 months and 805 children at 43
      months. RESULTS: The mean (standard deviation) percentages of energy from fat in
      each quartile at 18 months were 31.2 (2.8), 36.1 (0.9), 39.1 (0.8), and 43.1
      (2.2), corresponding to a fat intake in grams of 37.3 (8.1), 44.3 (8.1), 50.4
      (10.2), and 55.4 (12.7). The number of children failing to reach recommended
      intake levels for zinc and vitamin A fell with increasing fat intake, while the
      number of children consuming less than the recommendations for iron and vitamin C
      rose at both ages. Despite this, there was no association between fat intake at
      18 months and mean height or body mass index (BMI) at either 18 or 31 months. Fat
      intake at 43 months was also unassociated with concurrent or subsequent height or
      BMI. There was also no significant increase in the number of children falling
      below the tenth percentile for height or BMI as QFI fell. Mean ferritin levels at
      18 months fell in both sexes as QFI increased. Total cholesterol levels at 31
      months were significantly associated with QFI at 18 months, and rose from 3.99
      mmol/l in the lowest QFI in boys, to 4.31 mmol/l in the highest QFI. QFI at 43
      months was unassociated with cholesterol levels. CONCLUSIONS: These data do not
      suggest that fat intakes are an important determinant of growth in these
      children, even before the age of 2 years, or that children at the bottom of the
      range of fat intakes are experiencing delayed growth. On the other hand, there is
      also no evidence in this study that children on higher fat intakes are at a
      greater risk of becoming obese. In contrast to a number of US studies, we have
      not found children on lower fat intakes to have lower iron intakes-indeed higher
      fat intakes were associated with a greater chance of consuming less than the
      recommended intake of iron and with lower ferritin levels. The association of
      higher fat intakes with higher total cholesterol levels among boys is of concern,
      as there is evidence that the process of atherosclerosis begins during the
      preschool years.

PMID- 11533369
TI  - The practice of pediatric sleep medicine: results of a community survey.
AB  - OBJECTIVE: To assess knowledge, screening, evaluation, treatment practices, and
      attitudes regarding sleep disorders in children and adolescents in a large sample
      of community-based and academic pediatricians. DESIGN: Cross-sectional survey.
      PARTICIPANTS: Six hundred twenty-six pediatricians in Rhode Island,
      Massachusetts, and Connecticut. INTRUMENT: The Pediatric Sleep Survey, a 42-item
      questionnaire assessing general and specific sleep knowledge categories; clinical
      screening, diagnostic, and treatment practices for common pediatric sleep
      disorders; and practitioner attitudes regarding the impact of sleep disorders in
      the clinical setting and as a public health issue. RESULTS: On the knowledge
      section, the mean Total Knowledge score for the respondents was 18.1 +/- 3.5 out
      of 30 items, with 23.5% of the sample responding correctly on half or less of the
      items. Pediatricians scored highest on items relating to developmental and
      behavioral aspects of sleep and parasomnias, whereas the mean percentage of
      correct responses was <50% for items relating to sleep disordered breathing,
      excessive daytime sleepiness, and sleep movement disorders. Although only 16.5%
      and 18.2% of the sample reported not screening routinely for sleep disorders in
      infants and toddlers, this percentage rose to 43.9% in adolescents. Furthermore,
      only 38.3% regularly question the adolescents themselves about their sleep. Only
      about one quarter of the respondents screen toddlers and school-aged children for
      snoring. In evaluating and treating pediatric sleep problems, 53.2% of the sample
      never or rarely order overnight sleep studies to assess for obstructive sleep
      apnea and few use alternative treatment strategies, such as continuous positive
      airway pressure. A quarter of the sample at least occasionally recommends
      diphenhydramine and almost half suggests a psychological evaluation for children
      with night terrors. Finally, the percent of pediatricians rating the impact on
      children of sleep problems in a variety of domains as important or very important
      ranged from 49.7% (nonintentional injuries) to 92.6% (academic performance).
      However, only 46% of the sample felt confident or very confident about their own
      ability to screen for sleep problems, whereas 34.2% and 25.3% similarly rated
      their ability to evaluate and treat sleep problems in children. CONCLUSIONS: The
      results of this survey suggest that there are still significant gaps among
      practicing pediatricians both in basic knowledge about pediatric sleep disorders,
      and in the translation of that knowledge into clinical practice. Despite their
      acknowledgment of the importance of sleep problems, many pediatricians fail to
      screen adequately for them, especially in older children and adolescents.
      Additional educational efforts regarding pediatric sleep issues are warranted,
      and should be targeted at the medical school, postgraduate training, and
      continuing medical education levels.

PMID- 11533368
TI  - Age-related effects of genetic variation on lipid levels: The Columbia University
      BioMarkers Study.
AB  - OBJECTIVES: To examine the genotype:phenotype association in children compared
      with their parents. METHODS: Variations at 4 key gene loci, namely lipoprotein
      lipase (LPL S447X), hepatic lipase (HL -480C>T), cholesteryl ester transfer
      protein (CETP TaqIB), and apolipoprotein CIII (APOC3 -455T>C and -482C>T), were
      examined in children (n = 495) and their parents (n = 353) in the Columbia
      University BioMarkers Study, 1994 to 1998. RESULTS: The frequencies of the rare
      alleles of the HL -480C>T and APOC3 -455T>C and -482C>T (but not LPL S447X or
      CETP TaqIB) were significantly lower in non-Hispanic white participants compared
      with Hispanics. Overall, genotype effects seen in the adults were weaker in the
      children, although similar trends were seen. In an examination of the effect of
      body fat on the genotypic effects in the children, there was significant HL 
      480C>T:sum of skinfold interaction. CONCLUSIONS: All genotypes were associated
      with clear relationships to plasma lipid levels in adults, but the effects were
      weaker in their children, unless stressed by body fat. atherosclerosis,
      cardiovascular disease, child, lipids, genetics.

PMID- 11533371
TI  - Imperforate hymen: congenital or acquired from sexual abuse?
AB  - Imperforate hymen diagnosed beyond the newborn period may present a dilemma for
      the physician. Three case studies are reviewed in which children with the
      diagnoses of imperforate hymen presented for evaluation of suspected sexual
      abuse. Clear descriptions of genital anatomy documented at well-child visits may
      be critical to later interpretations of findings encountered during examinations
      for suspected sexual abuse.

PMID- 11533370
TI  - Toxicity of over-the-counter cough and cold medications.
AB  - Over-the-counter (OTC) cough and cold medications are marketed widely for relief
      of common cold symptoms, and yet studies have failed to demonstrate a benefit of
      these medications for young children. In addition, OTC medications can be
      associated with significant morbidity and even mortality in both acute overdoses
      and when administered in correct doses for chronic periods of time. Physicians
      often do not inquire about OTC medication use, and parents (or other caregivers)
      often do not perceive OTCs as medications. We present 3 cases of adverse outcomes
      over a 13-month period-including 1 death-as a result of OTC cough and cold
      medication use. We explore the toxicities of OTC cough and cold medications,
      discuss mechanisms of dosing errors, and suggest why physicians should be more
      vigilant in specifically inquiring about OTCs when evaluating an ill child.

PMID- 11533372
TI  - Severe osteopenia in a young boy with Kostmann's congenital neutropenia treated
      with granulocyte colony-stimulating factor: suggested therapeutic approach.
AB  - Kostmann's syndrome is a congenital disorder that causes an impairment of myeloid
      differentiation in the bone marrow characterized by severe neutropenia, which can
      be treated with recombinant human granulocyte colony-stimulating factor (G-CSF).
      We present the case of a 13-year-old boy with Kostmann's syndrome who was treated
      with recombinant human G-CSF from age 3.5 years. His growth and development was
      normal, although complicated by intermittent infections. Bone mineral density
      (BMD) measurement revealed severe osteopenia at the spine and hips (lumbar spine
      BMD 0.486 g/cm(2); Z score -3.6), and he was referred to the Endocrine Service.
      Relevant laboratory evaluation showed a pretreatment ionized calcium level at the
      upper limit of normal (1.28 mmol/L; range: 1.13-1.32 mmol/L), suppressed intact
      parathyroid hormone (iPTH) level (12 pg/mL; range: 10-65 pg/mL), and a low 1,25
      dihydroxy vitamin D level (21 pg/mL; range: 24-65 pg/mL). He had evidence of
      increased bone turnover evidenced by elevated urinary deoxypyridinoline (DPD)
      cross-links (46.9 nmol/mmol creatinine; range: 2-34 nmol/mmol creatinine) and a
      simultaneous increase in markers of bone formation with elevated osteocalcin
      level (200 ng/mL; normal: 20-80 ng/mL) and alkaline phosphatase level (236 IU/mL;
      normal: 38-126 IU/mL). Because of clinical concern for his skeletal health,
      bisphosphonate therapy with intravenous pamidronate was initiated. One month
      after treatment, the iPTH and DPD cross-links were in the normal range (54 pg/mL
      and 17.7 nmol/mmol creatinine, respectively) and the 1,25-dihydroxy vitamin D
      level was elevated (111 pg/mL). Four months after treatment, there was a striking
      increase in BMD at the lumbar spine (+30.86%), femoral necks (left, +20.02%;
      right, +17.98%), and total hips (left, +18.40%; right, +15.94%). Seven months
      after bisphosphonate therapy, his biochemical parameters showed a return toward
      pretreatment levels with increasing urinary DPD cross-links (28.7 nmol/mmol
      creatinine) and decreasing iPTH (26 pg/mL). However, the BMD continued to
      increase (8 months posttreatment), but the magnitude of the increment was
      attenuated (lumbar-spine, +4.8%; left total hip, +1.2% and right total hip
      +2.4%), relative to BMD at 4 months. Eight months after the initial treatment,
      his iPTH was suppressed at 14 pg/mL and he again received pamidronate (at a lower
      dose); 3 months later, he had an additional increase in BMD (lumbar spine +7.4%,
      left total hip +3.9%, right total hip +2.7%), relative to the previous study. We
      hypothesize that prolonged administration of G-CSF as treatment for Kostmann's
      syndrome is associated with increased bone resorption, mediated by osteoclast
      activation and leading to bone loss. In children, the resulting osteopenia can be
      successfully managed with antisreorptive bisphosphonate therapy with significant
      improvement in bone density. Measurements of biochemical parameters of bone
      turnover can be used to monitor the magnitude and duration of the therapeutic
      response and the need for BMD reassessment and, perhaps, retreatment.

PMID- 11533373
TI  - An orange a day keeps the doctor away: scurvy in the year 2000.
AB  - Scurvy has been known since ancient times, but the discovery of the link between
      the dietary deficiency of ascorbic acid and scurvy has dramatically reduced its
      incidence over the past half-century. Sporadic reports of scurvy still occur,
      primarily in elderly, isolated individuals with alcoholism. The incidence of
      scurvy in the pediatric population is very uncommon, and it is usually seen in
      children with severely restricted diets attributable to psychiatric or
      developmental problems. The condition is characterized by perifollicular
      petechiae and bruising, gingival inflammation and bleeding, and, in children,
      bone disease. We describe a case of scurvy in a 9-year-old developmentally
      delayed girl who had a diet markedly deficient in vitamin C resulting from
      extremely limited food preferences. She presented with debilitating bone pain,
      inflammatory gingival disease, perifollicular hyperkeratosis, and purpura. Severe
      hypertension without another apparent secondary cause was also present, which has
      been previously undescribed. The signs of scurvy and hypertension resolved after
      treatment with vitamin C. The diagnosis of scurvy is made on clinical and
      radiographic grounds, and may be supported by finding reduced levels of vitamin C
      in serum or buffy-coat leukocytes. The response to vitamin C is dramatic.
      Clinicians should be aware of this potentially fatal but easily curable condition
      that is still occasionally encountered among children.

PMID- 11533374
TI  - Screening for anemia in children: AAP recommendations--a critique.
AB  - The American Academy of Pediatrics (AAP) recommends screening for anemia between
      the ages of 9 to 12 months with additional screening between the ages of 1 and 5
      years for patients at risk. The screening may be universal or selective depending
      on the prevalence of iron deficiency anemia in the population. Improved infant
      rearing practices-including wider availability, acceptance, and use of iron
      fortified formulas; iron fortification of foods; and increased awareness of the
      importance of dietary iron supplementation especially early in life-have lead to
      significant decline in the incidence of anemia in the first year of life.
      However, incidence of iron deficiency and ensuing anemia in children between 1
      and 2 years continues to be significant and an important issue. Although iron
      deficiency may develop soon after cessation of or inadequate iron intake, anemia
      secondary to iron deficiency develops gradually over a period of several weeks to
      months. For children who have received/are receiving iron-fortified infant
      formulas and foods, hemoglobin screening at 9 to 12 months of age is
      inappropriate as there may not have been sufficient time to develop anemia,
      despite the rapid growth rate at this age. Widespread implementation of
      hemoglobin electrophoresis included in the neonatal metabolic screening programs
      in many states in the United States now has resulted in earlier diagnosis of
      hemoglobinopathies. Screening children at 9 to 12 months of age for
      hemoglobinopathies is somewhat redundant now. Screening for anemia before or
      around 1 year of age should continue to be important for communities and children
      at risk. Universal screening of toddlers at a later time allows sufficient time
      for nutritional anemia to become evident after the child has been weaned off iron
      fortified formulas, for the influence of toddler dietary fads to manifest, and
      for evaluation of tolerance of cow's milk protein. This may be addressed via 2
      approaches. The first involves postponing the currently recommended screening or
      an additional screening for anemia between 15 to 18 months of age. Determination
      of hemoglobin (or hematocrit) is not the optimal way to identify children at risk
      from effects of iron deficiency as it fails to identify patients who are iron
      deficient but are not anemic. Long-term psychomotor, behavioral, and
      developmental effects secondary to iron deficiency anemia are known but
      sufficient data are lacking regarding the role of iron deficiency without anemia.
      Development and evaluation of sensitive, specific, and cost-effective screening
      tools to identify children at risk for iron deficiency is important. Until such
      methods are instituted, the AAP should emphasize and recommend universal
      screening for anemia during the second year of life.

PMID- 11533375
TI  - Technical report: evidence for the diagnosis and treatment of acute uncomplicated
      sinusitis in children: a systematic overview.
AB  - OBJECTIVE: To evaluate and analyze the existing evidence for the diagnosis and
      treatment of acute uncomplicated sinusitis in children. DESIGN: A systematic
      overview and meta-analysis considered all pertinent studies with at least 10
      children younger than 18 years with acute symptoms of <30 days and without
      serious complications. OUTCOMES: Clinical improvement rates for intervention
      studies of antibiotics or ancillary measures; concordance of diagnostic tests
      (expressed as likelihood ratios). RESULTS: Of 1857 citations originally reviewed,
      we identified 21 qualifying studies, compared with 450 reports on complications
      of acute sinusitis and 233 nonsystematic reviews of the subject. The qualifying
      studies included 5 randomized, controlled trials and 8 case series on antibiotic
      therapy, 3 randomized, controlled trials on ancillary treatments, and 8 studies
      with information on diagnostic tests (including 3 therapeutic trials).
      Definitions and inclusion criteria were heterogeneous across studies. The pooled
      clinical improvement rate with antibiotics was 88% (177/202) in randomized,
      controlled trials and 92% (318/345) in nonrandomized studies; the improvement
      rates on no antibiotics were 60% and 80%, respectively. Improvement rates were
      significantly higher in nonrandomized studies (Mantel-Haenszel odds ratio: 1.79;
      95% CI: 1.05-3.04, stratified for use of antibiotics). Data on ancillary measures
      were sparse and heterogeneous. In studies comparing clinical findings with plain
      film radiography, the pooled rate of abnormal radiographic findings against a
      clinical diagnosis of sinusitis was 73% (596/814; range: 55% to 96% between
      studies). There was poor concordance between clinical criteria, plain
      radiographs, ultrasonography, computed tomography, and fluid on aspiration in all
      available paired assessments (all positive likelihood ratios were </=4 and all
      negative likelihood ratios were >/=0.2). CONCLUSIONS: Good, high-quality evidence
      for acute uncomplicated sinusitis in children is limited. Diagnostic modalities
      show poor concordance, and treatment options are based on inadequate data. More
      evidence is needed for defining the optimal treatment and diagnostic methods for
      this common condition.

PMID- 11533376
TI  - Point-counterpoint: sinusitis.

PMID- 11533377
TI  - Pediatric Perspectives: Observations of an Older Pediatrician: Supplementing
      Evidence-based Medicine.

PMID- 11533378
TI  - Poisoning potpourri.

PMID- 11533379
TI  - Index of suspicion.

PMID- 11533380
TI  - Delayed puberty.

PMID- 11533381
TI  - Visual diagnosis: an adolescent who has swelling of the foot.

PMID- 11533382
TI  - Counseling about bicycle safety.

PMID- 11533383
TI  - Scabies.

PMID- 11533384
TI  - Keeping practice current.

PMID- 11533386
TI  - Consumer & family information: electroconvulsive therapy.

PMID- 11533387
TI  - Datapoints: medicaid beneficiaries with a dual diagnosis: system responsibility
      and costs of care.

PMID- 11533388
TI  - State mental health policy: shifting resources to the community: closing the
      Illinois State Psychiatric Hospital for Adolescents in Chicago.

PMID- 11533389
TI  - Rehab rounds: an integrated psychological treatment program for schizophrenia.

PMID- 11533390
TI  - Emergency psychiatry: a review of assaults by patients against staff at
      psychiatric emergency centers.

PMID- 11533391
TI  - Evidence-based practice in child and adolescent mental health services.
AB  - The authors review the status, strength, and quality of evidence-based practice
      in child and adolescent mental health services. The definitional criteria that
      have been applied to the evidence base differ considerably across treatments, and
      these definitions circumscribe the range, depth, and extensionality of the
      evidence. The authors describe major dimensions that differentiate evidence-based
      practices for children from those for adults and summarize the status of the
      scientific literature on a range of service practices. The readiness of the child
      and adolescent evidence base for large-scale dissemination should be viewed with
      healthy skepticism until studies of the fit between empirically based treatments
      and the context of service delivery have been undertaken. Acceleration of the
      pace at which evidence-based practices can be more readily disseminated will
      require new models of development of clinical services that consider the practice
      setting in which the service is ultimately to be delivered.

PMID- 11533392
TI  - Effectiveness, transportability, and dissemination of interventions: what matters
      when?
AB  - The authors identify and define key aspects of the progression from research on
      the efficacy of a new intervention to its dissemination. They highlight the role
      of transportability questions that arise in that progression and illustrate key
      conceptual and design features that differentiate efficacy, effectiveness, and
      dissemination research. An ongoing study of the transportability of multisystemic
      therapy is used to illustrate independent and interdependent aspects of
      effectiveness, transportability, and dissemination studies. Variables relevant to
      the progression from treatment efficacy to dissemination include features of the
      intervention itself as well as variables pertaining to the practitioner, client,
      model of service delivery, organization, and service system. The authors provide
      examples of how some of these variables are relevant to the transportability of
      different types of interventions. They also discuss sample research questions,
      study designs, and challenges to be anticipated in the arena of transportability
      research.

PMID- 11533393
TI  - Mandated community treatment: beyond outpatient commitment.
AB  - Outpatient commitment, although often viewed as merely an extension of inpatient
      commitment, is only one of a growing array of legal tools used to mandate
      treatment adherence. The authors describe various forms of mandated community
      treatment. People with severe and chronic mental disorders often depend on goods
      and services provided by the social welfare system. Benefits disbursed by
      representative payees and the provision of subsidized housing have both been used
      as leverage to ensure treatment adherence. Many discharged patients are arrested
      for criminal offenses. Favorable disposition of their cases by a mental health
      court may be tied to participation in treatment. Under outpatient commitment
      statutes, judges can order committed patients to comply with prescribed
      treatment. Patients may attempt to maximize their control over treatment in the
      event of later deterioration by executing an advance directive. The ideological
      posturing that currently characterizes the field must be replaced by an evidence
      based approach.

PMID- 11533394
TI  - Housing satisfaction and service use by mentally ill persons in community
      integrated living arrangements.
AB  - OBJECTIVE: In response to provisions of the Omnibus Budget Reconciliation Act of
      1987 that sought to reduce the number of mentally ill persons in nursing homes,
      the Illinois Department of Human Services in 1989 developed small-scale
      residential treatment programs known as community integrated living arrangements.
      This study examined satisfaction with residential services and days of
      hospitalization among residents of these facilities. METHODS: Seventy-four
      residents from nine randomly selected community integrated living arrangement
      facilities were surveyed with the Quality of Life Interview to determine their
      satisfaction with their residence. Data on hospitalization before and after
      program placement were obtained from residents' charts and from an Illinois
      Department of Human Services database on utilization of state-operated
      facilities. RESULTS: Residents of community integrated living arrangement
      facilities had a mean rating of satisfaction with their residence of 5.2, "mostly
      satisfied," on a scale from 1 to 7. Residents with continuous supervision and
      those with intermittent supervision were equally pleased with their living
      arrangements. Residents' hospital use decreased from a mean of 47.7 days during
      the year before program placement to 5.3 days during their first year in the
      program. CONCLUSIONS: The level of satisfaction with the community integrated
      living arrangement residences was fairly high and was comparable to levels
      reported in related research on independent living arrangements. The decrease in
      residents' hospital use in the year after program placement suggests that the
      community integrated living arrangements help maintain severely mentally ill
      individuals in the community.

PMID- 11533395
TI  - Changes in mental health and service use after termination of SSI benefits.
AB  - OBJECTIVE: Supplemental Security Income (SSI) benefits for a substance abuse
      disability were terminated by federal legislation as of January 1, 1997. This
      study examined the changes in mental health and in the use of mental health
      services two years after the legislation was implemented among individuals who
      had been receiving benefits under this classification. METHODS: From a random
      sample of 400 SSI beneficiaries in Los Angeles, 253 were interviewed at the time
      the legislation took effect and again at 12-month, 18-month, and 24-month follow
      ups. The study subjects were characterized by income source after the legislation
      and by probable mental health diagnosis. Their use of mental health services was
      also measured. RESULTS: The mental health status of the participants remained
      unchanged between baseline and 24-month follow-up. The proportion who reported
      any use of mental health services decreased, primarily among those who continued
      receiving SSI benefits under a different classification. Among those who lost SSI
      benefits, emergency department visits and hospitalizations did not increase, and
      rates of outpatient visits remained the same. CONCLUSIONS: Contrary to
      expectations, the mental health status of individuals who had been receiving SSI
      benefits for a substance abuse disability did not worsen after the benefits were
      terminated. Local safety nets and reclassification under another disability may
      have mitigated the effects of the policy change. The results of this study
      underscore the need for longitudinal data to inform policy decisions.

PMID- 11533396
TI  - Variables associated with disparities in treatment of patients with schizophrenia
      and comorbid mood and anxiety disorders.
AB  - OBJECTIVE: The study compared self-reported comorbid affective and anxiety
      disorder diagnoses and treatments of African-American and Caucasian subjects in a
      large sample of patients who had a diagnosis of schizophrenia. METHODS: A total
      of 685 patients receiving treatment for schizophrenia were interviewed as part of
      the Schizophrenia Patient Outcomes Research Team study. The associations of race
      with past and current diagnoses and with current treatment for depression, mania,
      and anxiety disorders were assessed with multivariate analyses. RESULTS: African
      Americans were significantly less likely than Caucasians to report having a past
      or current diagnosis of depression, manic-depression, or anxiety disorder and to
      be receiving current treatment for these disorders. Gender, education, and
      marital status were also associated with presence of a comorbid diagnosis and
      receipt of treatment. CONCLUSIONS: The study suggests the possibility of racial
      and other disparities in the diagnosis and treatment of patients with
      schizophrenia and comorbid affective and anxiety disorders. Although various
      causal explanations are plausible, all point toward the need for enhanced cross
      cultural competence at all levels of mental health care, especially in the
      diagnosis and treatment of comorbid psychiatric illnesses.

PMID- 11533397
TI  - Relationships between counseling rapport and drug abuse treatment outcomes.
AB  - OBJECTIVE: This study examined the association between counseling rapport and
      drug abuse treatment outcomes. METHODS: Two cohorts of outpatients who were being
      treated with methadone in four cities were studied. Cohort 1 comprised 354
      patients in community-based nonprofit programs, and cohort 2 comprised 223
      patients from a private for-profit program. Logistic regression analyses were
      used to assess the importance of counseling rapport as a predictor of drug use
      and criminality relative to treatment retention in the index treatment,
      satisfaction with treatment, and whether additional treatment was received after
      the index treatment. RESULTS: In both cohorts, ratings made by counselors, during
      treatment, of therapeutic involvement and relationships with patients provided a
      useful measure of counseling rapport. A lower level of rapport during treatment
      predicted worse post-index treatment outcomes, including more cocaine use and
      criminality, both by itself and after adjustment for treatment retention,
      satisfaction with treatment, and post-index treatment status. Counseling
      strategies were associated with the development of counseling rapport.
      CONCLUSIONS: Counseling rapport is a vital part of the therapeutic process and
      helps explain why and when treatment is effective. It contributes explicitly to
      the prediction of outcomes, apart from treatment retention, and accounts in part
      for the usual association between treatment retention and outcomes.

PMID- 11533398
TI  - Patient satisfaction, use of services, and one-year outcomes in publicly funded
      substance abuse treatment.
AB  - OBJECTIVE: This longitudinal study examined the relationships among patient
      satisfaction with substance abuse services, service use, and clinical and
      employment outcomes. METHODS: Interviews were conducted with 502 adults who were
      beginning outpatient or residential treatment for substance abuse in a managed
      care plan in Oregon or in fee-for-service plans in Washington State. The
      participants were reinterviewed after six months and after one year. Measures of
      satisfaction and use of services were assessed at six months and clinical
      outcomes at one year with the Addiction Severity Index. Multivariate regression
      analyses were used to estimate the relationship between satisfaction and service
      use and the relationships among satisfaction, use, and one-year outcomes when
      baseline characteristics were held constant. RESULTS: The final sample included
      310 individuals (62 percent) who completed interviews at the three time points.
      Compared with those who were excluded because of missing data, the patients in
      the final sample were more likely to be white, to be better educated, to be in
      outpatient treatment, and to live in Oregon and less likely to be homeless. No
      significant differences were observed in baseline symptoms between the two
      groups. Satisfaction with access and effectiveness of services predicted service
      use at six months. Service use, satisfaction with access, and satisfaction with
      effectiveness were significantly associated with abstinence from substance use at
      one year. Neither patient satisfaction nor use of services was related to other
      outcomes, including employment and the presence of psychiatric symptoms.
      CONCLUSIONS: Although causation cannot be determined, the results of this study
      suggest that patient satisfaction is related to both use of services and
      abstinence from substance use. Longitudinal research using more detailed measures
      of satisfaction is needed to sort out the complex relationship between
      satisfaction and service use and the direct and indirect influences of these
      variables on outcomes.

PMID- 11533399
TI  - Training, communication, and information needs of mental health counselors in the
      United Kingdom.
AB  - OBJECTIVE: This national cross-sectional survey investigated the communication
      and information needs of mental health counselors in the United Kingdom as well
      as the difficulty these professionals experienced in obtaining help from other
      mental health care providers. METHODS: Mailed questionnaires were sent to a
      random sample of 400 registered counselors. A total of 230 counselors returned
      the questionnaire, for a response rate of 58 percent. Descriptive statistics,
      correlations, and multiple logistic regression analysis were used to analyze the
      results. RESULTS: The respondents reported being in contact mostly with other
      counselors, general practitioners, and psychiatrists. Most of the respondents (80
      percent) reported other counselors to be quite or extremely helpful when
      consulted; the proportions were much lower for other types of practitioners,
      especially general practitioners and psychiatrists. Reported barriers to
      coordination of counseling services included lack of time and communication
      problems with other professionals. A total of 160 respondents (70 percent)
      reported not having the necessary training or skills for managing severe cases of
      mental illness, and 168 (73 percent) indicated that they had a need for
      information about mental illness. Predictors of information needs were a lack of
      the necessary skills for managing severe cases, contact with mostly other
      counselors, and a desire for information about illness, the services of voluntary
      agencies (agencies with charity status and other nonstatutory organizations), and
      mental health law. CONCLUSIONS: This survey highlighted the importance of meeting
      the information, communication, and training needs of mental health counselors in
      the United Kingdom in order for counselors to provide high-quality counseling
      services.

PMID- 11533401
TI  - Lessons learned from trends in psychotropic drug expenditures in a canadian
      province.
AB  - Although prescription drug prices are lower in Canada than in the United States,
      trends indicate that there has nevertheless been a steep increase in expenditures
      on psychotropic drugs. Between 1992 and 1998, such expenditures increased by 216
      percent; 61 percent of these expenditures were on antidepressants, 33 percent on
      antipsychotics, and less than 7 percent on anxiolytics. Most of the increase in
      costs in Canada is attributable to a greater use of newer agents and the higher
      prices of these agents. These trends are a reminder not only that the use of
      newer, more expensive psychotherapeutic agents has become a widely embraced part
      of care but also that lower drug prices do not necessarily insulate a health care
      system from rising expenditures. The authors' findings prompt the questions of
      whether the use of these newer agents meets practice guidelines and whether there
      are ways to control the increases in drug expenditures while ensuring high
      quality care.

PMID- 11533400
TI  - Delays in adopting evidence-based dosages of conventional antipsychotics.
AB  - By the 1980s, strong research evidence had emerged supporting the use of moderate
      doses of conventional antipsychotics-between 300 and 1,000 mg of chlorpromazine
      equivalent daily. We conducted a cross-sectional study of dosages of
      antipsychotics prescribed for 936 veterans with schizophrenia in 14 facilities
      between 1991 and 1995. Only 52 percent of these patients received prescriptions
      for recommended dosages; dosages were below the recommended range for 20 percent
      and above the range for 28 percent. African Americans were more likely than
      others to have received high dosages. These data suggest that there was
      considerable delay in the adoption of evidence-based dosing of conventional
      antipsychotics. Efforts must be made to transfer research findings more rapidly
      into practice.

PMID- 11533402
TI  - Refill patterns of atypical and conventional antipsychotic medications at a
      national retail pharmacy chain.
AB  - This study examined whether patients who received prescriptions for conventional
      and atypical antipsychotics in routine outpatient care continued medication
      therapy. Prescription refill records of more than 25,000 patients from a national
      retail pharmacy chain were surveyed during a full eight-month period. At the
      start of the ninth month, 48 percent of the patients taking conventional agents
      were continuing therapy. The overall rate for those taking atypical agents was 44
      percent; however, the rate for those taking clozapine was 71 percent. Atypical
      agents, despite their improved side effect profile, were not associated with
      higher rates of continued treatment. A highly supervised medication
      administration process, frequent patient-provider contact, and favorable patient
      selection may help explain the higher rate among patients taking clozapine.

PMID- 11533404
TI  - Follow-up for parasuicidal patients.

PMID- 11533403
TI  - Problematic substance use, depressive symptoms, and gender in primary care.
AB  - This study determined the frequency of problematic substance use and of
      counseling about drug and alcohol use among 867 women and 320 men who reported
      symptoms of depression in managed primary care clinics. Seventy-two (8.3 percent)
      of the women and 61 (19 percent) of the men reported hazardous drinking; 228
      (26.3 percent) of the women and 94 (29.4 percent) of the men reported problematic
      drug use, including use of illicit drugs and misuse of prescription drugs. Only
      17 (13.9 percent) of the patients who reported hazardous drinking and 18 (6.6
      percent) of those who reported problematic drug use received counseling about
      drug or alcohol use during their last primary care visit. Men were significantly
      more likely than women to have received counseling about drug or alcohol use from
      their primary care practitioner.

PMID- 11533405
TI  - The challenges of split treatment.

PMID- 11533407
TI  - Substance use and medication treatment.

PMID- 11533410
TI  - Cotard's syndrome in a homeless man.

PMID- 11533412
TI  - Arrhythmia and antipsychotic medications.

PMID- 11533414
TI  - Autocastration and psychosis.

PMID- 11533415
TI  - Developing professional ability to involve patients in their care: pull or push?

PMID- 11533416
TI  - Ensuring patients' satisfaction with information about their medicines.

PMID- 11533417
TI  - What changes are needed to provide better standards of stroke care?

PMID- 11533418
TI  - Quality of clinical care in general practice.

PMID- 11533419
TI  - Getting journals rapidly to developing countries: opportunities through the
      internet.

PMID- 11533420
TI  - The Satisfaction with Information about Medicines Scale (SIMS): a new measurement
      tool for audit and research.
AB  - OBJECTIVE: To develop and examine the psychometric properties of the Satisfaction
      with Information about Medicines Scale (SIMS), a new 17-item tool designed to
      assess the extent to which patients feel they have received enough information
      about prescribed medicines. METHODS: Patients from eight diagnostic categories
      were recruited at hospitals in London and Brighton and completed the SIMS
      questionnaire during hospital admission or attendance at outpatient clinic
      appointments. The SIMS was evaluated in terms of its ease of use, internal
      consistency, test-retest reliability, and criterion related validity using
      existing self-report measures of adherence and patient beliefs about medicines.
      RESULTS: The SIMS was well accepted by patients in a variety of clinical settings
      and showed satisfactory internal consistency and test-retest reliability. As
      predicted, higher levels of satisfaction with medicines information were
      associated with higher levels of reported adherence, and lower levels of
      satisfaction were associated with stronger concerns about the potential adverse
      effects of medicines, providing evidence of criterion related validity.
      CONCLUSION: The SIMS performed well on a number of psychometric indicators and
      shows promise as a tool for audit (measuring patients' satisfaction with
      information about their prescribed medicines), research (evaluating current or
      new forms of information provision), and clinical practice (identifying the
      information needs of individual patients and as an aid to planning medicine
      related consultations).

PMID- 11533421
TI  - National stroke audit: a tool for change?
AB  - OBJECTIVES: To describe the standards of care for stroke patients in England,
      Wales and Northern Ireland and to determine the power of national audit, coupled
      with an active dissemination strategy to effect change. DESIGN: A national audit
      of organisational structure and retrospective case note audit, repeated within 18
      months. Separate postal questionnaires were used to identify the types of change
      made between the first and second round and to compare the representativeness of
      the samples. SETTING: 157 trusts (64% of eligible trusts in England, Wales, and
      Northern Ireland) participated in both rounds. PARTICIPANTS: 5589 consecutive
      patients admitted with stroke between 1 January 1998 and 31 March 1998 (up to 40
      per trust) and 5375 patients admitted between 1 August 1999 and 31 October 1999
      (up to 40 per trust). Audit tool-Royal College of Physicians Intercollegiate
      Working Party stroke audit. RESULTS: The proportion of patients managed on stroke
      units rose between the two audits from 19% to 26% with the proportion managed on
      general wards falling from 60% to 55% and those managed on general rehabilitation
      wards falling from 14% to 11%. Standards of assessment, rehabilitation, and
      discharge planning improved equally on stroke units and general wards, but in
      many aspects remained poor (41% formal cognitive assessment, 46% weighed once
      during admission, 67% physiotherapy assessment within 72 hours, 24% plan
      documented for mood disturbance, 36% carers' needs assessed separately).
      CONCLUSIONS: Nationally conducted audit linked to a comprehensive dissemination
      programme was effective in stimulating improvements in the quality of care for
      patients with stroke. More patients are being managed on stroke units and
      multidisciplinary care is becoming more widespread. There remain, however, many
      areas where standards of care are low, indicating a need for investment of skills
      and resources to achieve acceptable levels.

PMID- 11533422
TI  - Systematic review of studies of quality of clinical care in general practice in
      the UK, Australia and New Zealand.
AB  - OBJECTIVES: Little is known about the quality of clinical care provided outside
      the hospital sector, despite the increasingly important role of clinical
      generalists working in primary care. In this study we aimed to summarise
      published evaluations of the quality of clinical care provided in general
      practice in the UK, Australia, and New Zealand. DESIGN: A systematic review of
      published studies assessing the quality of clinical care in general practice for
      the period 1995-9. SETTING: General practice based care in the UK, Australia, and
      New Zealand. Main outcome measures-Study design, sampling strategy and size,
      clinical conditions studied, quality of care attained for each condition
      (compared with explicit or implicit standards for the process of care), and
      country of origin for each study. RESULTS: Ninety papers fulfilled the entry
      criteria for the review, 80 from the UK, six from Australia, and four from New
      Zealand. Two thirds of the studies assessed care in self-selected practices and
      20% of the studies were based in single practices. The majority (85.5%) examined
      the quality of care provided for chronic conditions including cardiovascular
      disease (22%), hypertension (14%), diabetes (14%), and asthma (13%). A further
      12% and 2% examined preventive care and acute conditions, respectively. In almost
      all studies the processes of care did not attain the standards set out in
      national guidelines or those set by the researchers themselves. For example, in
      the highest achieving practices 49% of diabetic patients had had their fundii
      examined in the previous year and 47% of eligible patients had been prescribed
      beta blockers after an acute myocardial infarction. CONCLUSIONS: This study
      adopts an overview of the magnitude and the nature of clinical quality problems
      in general practice in three countries. Most of the studies in the systematic
      review come from the UK and the small number of papers from Australia and New
      Zealand make it more difficult to draw conclusions about the quality of care in
      these two countries. The review helps to identify deficiencies in the research,
      clinical and policy agendas in a part of the health care system where quality of
      care has been largely ignored to date. Further work is required to evaluate the
      quality of clinical care in a representative sample of the population, to
      identify the reasons for substandard care, and to test strategies to improve the
      clinical care provided in general practice.

PMID- 11533423
TI  - Pragmatic randomised trial to evaluate the use of patient held records for the
      continuing care of patients with cancer.
AB  - OBJECTIVE: To evaluate the use of a multidisciplinary record held by patients
      with cancer in the community. DESIGN: Pragmatic randomised controlled trial.
      SETTING: The environs of Swansea in south west Wales. PARTICIPANTS: 501 patients
      under the care of the Department of Oncology, Singleton Hospital, Swansea.
      INTERVENTION: A patient held record used by the patient and healthcare
      professionals. Main outcome measures-Health related quality of life (EORTC QLQ
      C30) measured at entry into the study and at 6 months; patients' views at 6
      months; healthcare professionals' views collected after the completion of patient
      follow up; NHS resource and booklet use. RESULTS: 1148 patients were eligible for
      the study; 501 were recruited (44%) and 344 completed the study (172 in each
      group). There was no significant difference between the two groups in change in
      quality of life or NHS resource use. The patient held record did not have an
      impact on communication but was significantly helpful to patients in preparing
      for appointments, reducing difficulties in monitoring their own progress, and
      helping them to feel more in control (p<0.05). Fifty three percent of patients
      would have preferred not to have a patient held record. There was a low level of
      use of the record by healthcare professionals but most of those who remembered
      using it indicated that they would prefer patients to have it. CONCLUSIONS: The
      patient held record is valued by some patients and professionals but has no
      significant impact on the quality of life of patients or NHS resource use. It has
      a positive impact on quality by helping patients feel more in control and prepare
      for meetings with healthcare staff. Patients who find it useful tend to be
      younger and have more professionals involved in their care. It is recommended
      that it should be made available to patients on request and used by them
      according to need.

PMID- 11533424
TI  - Development of guidelines to facilitate improved support of South Asian carers by
      primary health care teams.
AB  - BACKGROUND: Evidence based guidelines are regarded as an appropriate basis for
      providing effective health care, but few guidelines incorporate the views of
      users such as carers. AIM: To develop guidelines to assist primary health care
      teams (PHCTs) in their work with carers within South Asian communities. METHODS:
      The guidelines were drawn up by a development group consisting of members of
      teams in areas with South Asian communities (Leicester and Bradford). The teams
      were invited to make their recommendations based on a systematic review of
      literature on minority ethnic carers and the findings of a study of the needs and
      experiences of local South Asian carers. A grading system was devised to enable
      the teams and a group of expert peer reviewers to assess the quality of evidence
      in support of each recommendation. RESULTS: The teams agreed seven
      recommendations, graded according to available evidence and strength of opinion.
      External peer review supported the PHCTs' interpretation of evidence and their
      recommendations. The recommendations included consideration of communication and
      information for carers, coordination of care within teams, and recognition by
      team members of the roles of carers and their cultural and religious beliefs.
      CONCLUSION: There are particular steps that PHCTs can take to improve their
      support of South Asian carers. It is possible to develop guidelines that take
      users' views into account and incorporate evidence from qualitative studies.

PMID- 11533425
TI  - Expert consensus on the desirable characteristics of review criteria for
      improvement of health care quality.
AB  - OBJECTIVES: To identify the desirable characteristics of review criteria for
      quality improvement and to determine how they should be selected. BACKGROUND:
      Review criteria are the elements against which quality of care is assessed in
      quality improvement. Use of inappropriate criteria may impair the effectiveness
      of quality improvement activities and resources may be wasted in activities that
      fail to facilitate improved care. METHODS: A two round modified Delphi process
      was used to generate consensus amongst an international panel of 38 experts. A
      list of 40 characteristics of review criteria, identified from literature
      searches, was distributed to the experts who were asked to rate the importance
      and feasibility of each characteristic. Comments and suggestions for
      characteristics not included in the list were also invited. RESULTS: The Delphi
      process refined a comprehensive literature based list of 40 desirable
      characteristics of review criteria into a more precise list of 26 items. The
      expert consensus view is that review criteria should be developed through a well
      documented process involving consideration of valid research evidence, possibly
      combined with expert opinion, prioritisation according to health outcomes and
      strength of evidence, and pilot testing. Review criteria should also be
      accompanied by full clear information on how they might be used and how data
      might be collected and interpreted. CONCLUSION: The desirable characteristics for
      review criteria have been identified and will be of use in the development,
      evaluation, and selection of review criteria, thus improving the cost
      effectiveness of quality improvement activities in healthcare settings.

PMID- 11533426
TI  - Enhancing causal interpretations of quality improvement interventions.
AB  - In an era of chronic resource scarcity it is critical that quality improvement
      professionals have confidence that their project activities cause measured
      change. A commonly used research design, the single group pre-test/post-test
      design, provides little insight into whether quality improvement interventions
      cause measured outcomes. A re-evaluation of a quality improvement programme
      designed to reduce the percentage of bilateral cardiac catheterisations for the
      period from January 1991 to October 1996 in three catheterisation laboratories in
      a north eastern state in the USA was performed using an interrupted time series
      design with switching replications. The accuracy and causal interpretability of
      the findings were considerably improved compared with the original evaluation
      design. Moreover, the re-evaluation provided tangible evidence in support of the
      suggestion that more rigorous designs can and should be more widely employed to
      improve the causal interpretability of quality improvement efforts. Evaluation
      designs for quality improvement projects should be constructed to provide a
      reasonable opportunity, given available time and resources, for causal
      interpretation of the results. Evaluators of quality improvement initiatives may
      infrequently have access to randomised designs. Nonetheless, as shown here, other
      very rigorous research designs are available for improving causal
      interpretability. Unilateral methodological surrender need not be the only
      alternative to randomised experiments.

PMID- 11533427
TI  - Informing, communicating and sharing decisions with people who have cancer.

PMID- 11533429
TI  - Engaging patients in decisions: a challenge to health care delivery and public
      health.

PMID- 11533430
TI  - Measuring patients' preferences for treatment and perceptions of risk.

PMID- 11533431
TI  - Understanding risk and lessons for clinical risk communication about treatment
      preferences.
AB  - This paper defines risk and its component elements and describes where clinical
      practice may be starting from in terms of what is reported in the literature
      about understanding risks and the information requirements of consumers. It notes
      briefly how theoretical models in the literature contribute to our understanding
      by providing a basis from which to summarise current evidence about the effects
      of healthcare interventions which address risks and risk behaviour. The
      situations or types of interventions in which risk related interventions are most
      effective are described, but a significant caveat is noted about the types of
      outcomes which have been reported in the literature and which are most
      appropriate to evaluate. The effects of "framing" variations in the information
      given to consumers and the ethical dilemmas these raise for a debate about
      "informed choice" in healthcare programmes are discussed. In response to both the
      practical and ethical dilemmas that arise from the current evidence, some of the
      areas where attention should be focused in the future are outlined so that both
      health gain and informed choice might be achieved. These include the use of
      decision aids, although their implementation is not widespread at present.
      Lessons from the current literature on how further progress can be made towards
      improved communication, discussion between professionals and consumers, and
      enhancing informed choice are discussed.

PMID- 11533432
TI  - The extent of patients' understanding of the risk of treatments.
AB  - The scientific understanding of how people perceive and code risks and then use
      this information in decision making has progressed greatly in the last 20 years.
      There is considerable evidence that people employ simplifying heuristics in
      judgement and decision making. These heuristics may lead to bias in how people
      interpret information. However, much of our understanding of risk perception is
      based on laboratory studies. It is much less clear whether risk perception in the
      real world (as in the case of medical treatments) exhibits the same patterns and
      biases. This paper reviews the published literature on risk perception in
      patients who face substantial treatment risks. It examines how accurate patients'
      perception of risk is, what factors affect the perception of risk, and several
      possible explanations for why patients' risk perception is not always accurate.

PMID- 11533433
TI  - Importance of risk communication and decision making in cardiovascular conditions
      in older patients: a discussion paper.
AB  - Atrial fibrillation and aortic stenosis commonly present doctors and patients
      with difficult decisions about the risks and benefits of treatment options and
      are both often inappropriately undertreated. Patients may be confused by risk
      information and doctors may be aware of patients' limitations and use this to
      manipulate choices to the ones desired by the doctors. This paper examines the
      importance of risk communication and discusses difficulties that can arise in
      decision making in these two common cardiovascular conditions.

PMID- 11533434
TI  - Suffering in deference: a focus group study of older cardiac patients'
      preferences for treatment and perceptions of risk.
AB  - OBJECTIVES: To explore older people's experiences of health care in relation to
      their medical condition (ischaemic heart disease), their understanding of health
      risks, treatment preferences, and the impact of different treatments on their
      quality of life. DESIGN: Qualitative study based on five focus groups. SETTING:
      Five local heart support groups across London. PARTICIPANTS: 38 patients aged 56
      and over who were members of local heart support groups, diagnosed with ischaemic
      heart disease. MAIN OUTCOME MEASURE: Analysis of patients' narratives to identify
      key themes and issues using the framework method of qualitative data analysis.
      RESULTS: Cardiac patients would prefer to follow the cardiologist's
      recommendation for treatment, based on their medical expertise. If offered a
      choice, many said they would prefer to take medication, at least initially, as
      they would rather not undergo surgery. However, they accepted that, depending on
      their medical condition, they might not have a choice. Other factors that
      participants said affected their choice of treatments included their state of
      health, treatment outcomes, families' feelings, their age, and the previous
      number of operations they had undergone. They found it difficult to discuss risk
      in terms of numbers; most felt that a 3% risk of death from surgery was low.
      Instead, they discussed risk in terms of likelihood of treatment restoring
      quality of life. Patients expressed the fear that medication was not a cure and
      that surgical revascularisation is a traumatic experience that does not
      necessarily last forever. Participants felt that they needed further information
      on the impact of surgery and medication to make a more informed choice. Other
      barriers they felt they had faced in being treated were problems in accessing
      cardiologists and age discrimination. CONCLUSION: It was apparent from these
      focus groups that few patients were involved in medical decision making about
      their treatment. Most preferred the doctor to make the decision and did want to
      be involved. Despite their experiences as cardiac patients, they required much
      more information about treatment options for their condition before being able to
      make informed choices, where appropriate. Improved access to specialist care
      (cardiologists) and equal treatment by age are also required before patients'
      preferences can be elicited in practice.

PMID- 11533435
TI  - Informed consent: moral necessity or illusion?
AB  - There is a professional and legal consensus about the clinical duty to obtain
      informed consent from patients before treating them. This duty is a reflection of
      wider cultural values about the moral importance of respect for individual
      autonomy. Recent research has raised practical problems about obtaining informed
      consent. Some patients have cognitive and emotional problems with understanding
      clinical information and do not apparently wish to participate in making
      decisions about their treatment. This paper argues that such research does not
      undermine their potential to provide informed consent. Rather, sufficient
      resources are required to create better communication skills among clinicians and
      more effective educational materials for patients. Finally, cognitive and
      emotional inequality among patients is maintained to be a reflection of wider
      social and economic inequalities. Researchers who take the right to informed
      consent seriously should also address these.

PMID- 11533436
TI  - Variability in patient preferences for participating in medical decision making:
      implication for the use of decision support tools.
AB  - While there is an increasing emphasis on patient empowerment and shared decision
      making, evidence suggests that many patients do not wish to be involved in
      decisions about their own care. Previous research has found patient preferences
      for involvement in decision making to vary with age, socioeconomic status,
      illness experience, and the gravity of the decision. Furthermore, there is
      evidence that certain patients may experience disutility from being involved in
      decision making about the treatment of their health problems. We discuss the
      implications of these findings for the use of decision support tools and the
      difficulties of targeting their use towards those patients most likely to
      benefit. We argue that patients may be ill informed about what participation in
      decision making actually entails and unaware of the benefits they stand to gain
      by articulating their preferences to their clinician. Furthermore, clinicians are
      not good at accurately assessing patients' preferences, while patients may have
      unrealistic expectations about their clinician's ability to "know what is best"
      for them. Further research is required to understand variations in patients'
      preferences for information and involvement in decision making, and the factors
      that influence them.

PMID- 11533437
TI  - How do patients' treatment preferences compare with those of clinicians?
AB  - The shared model of medical decision making has been proposed as the preferred
      method of determining patients' treatment. However, agreement may be more
      difficult to achieve if patients' and clinicians' preferences are polarised. The
      aim of this paper is to explore how closely patients and clinicians agree in
      their preferences for different treatment options. Only studies that made
      quantifiable estimates of preferences were included. There is some evidence that
      patients and health professionals often do not agree on treatment preference in
      the areas of cardiovascular disease, cancer, obstetrics and gynaecology, and
      acute respiratory illness. However, the magnitude and direction of these
      differences vary and may depend on the condition of interest. Most of the
      research to date is cross sectional; longitudinal research is required to
      investigate whether preferences change over time and are related to treatment
      choice, adherence to medication if taken, and health outcomes.

PMID- 11533438
TI  - Differences in belief about likely outcomes account for differences in doctors'
      treatment preferences: but what accounts for the differences in belief?
AB  - Doctors, patients, and their relatives face a complex decision when there are
      multiple treatment options that differ in their profiles of risk and benefit over
      time. Doctors from a single specialist paediatric cardiac unit participated in a
      correlational study that used a novel tool (subjective multi-state survival
      graphs) to elicit their beliefs about the likely outcome of different treatments.
      Doctors' preferences were more closely related to their beliefs about long term,
      rather than short term, outcomes. This is consistent with placing greater value
      on far future than on immediate life years, highlighting the importance of
      incorporating patients' values for these outcomes into decisions of this kind.
      Beliefs about likely outcomes differed with whether or not doctors encountered
      former paediatric patients who were now adults, illustrating the difficulty of
      deciding what risk information should be available when the evidence base on
      outcomes is limited. Some problems of risk communication are identified, and the
      value of multi-state survival graphs as an aid to communication is discussed.

PMID- 11533439
TI  - Understanding patients' preferences for treatment: the need for innovative
      methodologies.
AB  - Treatment selection is now much more consumer driven than in the past. However,
      there is a need to develop investigative methodological approaches that are
      sensitive to differences in patient preferences if full account is to be taken of
      what the patient sees as the best option in terms of different possible
      treatments available for a particular condition. Previous attitude research has
      been criticised because it does not provide insight into reasons why people hold
      different preferences or beliefs. A methodology is described which allows people
      to describe their concerns and values associated with different treatment options
      in their own words. This is the repertory grid method of eliciting personal
      constructs used in conjunction with generalised Procrustes analysis (GPA). An
      example of the use of this methodology is provided, drawn from research directed
      towards understanding people's beliefs about genetic technologies. A possible
      application of the method to understanding treatment preferences related to type
      2 diabetes is also discussed. It is concluded that the use of innovative
      methodologies is essential if our understanding of patient preferences regarding
      treatment options is to have a significant impact on patient quality of life.

PMID- 11533440
TI  - Use of discrete choice experiments to elicit preferences.
AB  - This paper considers the application of discrete choice experiments for eliciting
      preferences in the delivery of health care. Drawing upon the results from a
      recently completed systematic review, the paper summarises the application of
      this technique in health care. It then presents a case study applying the
      technique to rheumatology outpatient clinics. 200 patients were questioned about
      the importance of six attributes: staff seen (junior doctor or specialist nurse);
      time in waiting area; continuity of contact with same staff; provision of a phone
      in/advice service; length of consultation; and change in pain levels. The
      systematic review indicated that discrete choice experiments have been applied to
      a wide number of areas and a number of methodological issues have been addressed.
      Consistent with this literature, the case study found evidence of both
      rationality and theoretical validity of responses. The approach was used to
      establish the relative importance of different attributes, how individuals trade
      between these attributes, and overall benefit scores for different clinic
      configurations. The value of attributes was estimated in terms of time, and this
      was converted to a monetary measure using the value of waiting time for public
      transport. Discrete choice experiments represent a potentially useful instrument
      for eliciting preferences. Future methodological work should explore issues
      related to the experimental design of the study, methods of data collection and
      analysis, and satisfaction with the economic axioms of the instrument.
      Collaborative work with psychologists and qualitative researchers will prove
      useful in this research agenda.

PMID- 11533441
TI  - Preferences and understanding their effects on health.
AB  - Preference for a particular intervention may, possibly via complicated pathways,
      itself confer an outcome advantage which will be subsumed in unblind randomised
      trials as part of the measured effectiveness of the intervention. Where more
      attractive interventions are compared with less attractive ones, any difference
      could therefore be a consequence of attractiveness and not its intrinsic worth.
      For health promotion interventions this is clearly important, but we cannot tell
      how important it is for therapeutic interventions without special studies to
      measure or refute such effects. These are difficult to do and are complex. Until
      the therapeutic effects of preference itself are more clearly understood,
      understanding the true therapeutic effects will be compromised, at least in
      principle.

PMID- 11533442
TI  - Structure of Arp2/3 complex in its activated state and in actin filament branch
      junctions.
AB  - The seven-subunit Arp2/3 complex choreographs the formation of branched actin
      networks at the leading edge of migrating cells. When activated by Wiskott
      Aldrich Syndrome protein (WASp), the Arp2/3 complex initiates actin filament
      branches from the sides of existing filaments. Electron cryomicroscopy and three
      dimensional reconstruction of Acanthamoeba castellanii and Saccharomyces
      cerevisiae Arp2/3 complexes bound to the WASp carboxy-terminal domain reveal
      asymmetric, oblate ellipsoids. Image analysis of actin branches indicates that
      the complex binds the side of the mother filament, and Arp2 and Arp3 (for actin
      related protein) are the first two subunits of the daughter filament. Comparison
      to the actin-free, WASp-activated complexes suggests that branch initiation
      involves large-scale structural rearrangements within Arp2/3.

PMID- 11533443
TI  - High-temperature superconductivity in lattice-expanded C60.
AB  - C60 single crystals have been intercalated with CHCl3 and CHBr3 in order to
      expand the lattice. High densities of electrons and holes have been induced by
      gate doping in a field-effect transistor geometry. At low temperatures, the
      material turns superconducting with a maximum transition temperature of 117 K in
      hole-doped C60/CHBr3. The increasing spacing between the C60 molecules follows
      the general trend of alkali metal-doped C60 and suggests routes to even higher
      transition temperatures.

PMID- 11533445
TI  - Gene duplication and evolution.

PMID- 11533444
TI  - Phosphorylation-dependent ubiquitination of cyclin E by the SCFFbw7 ubiquitin
      ligase.
AB  - Cyclin E binds and activates the cyclin-dependent kinase Cdk2 and catalyzes the
      transition from the G1 phase to the S phase of the cell cycle. The amount of
      cyclin E protein present in the cell is tightly controlled by ubiquitin-mediated
      proteolysis. Here we identify the ubiquitin ligase responsible for cyclin E
      ubiquitination as SCFFbw7 and demonstrate that it is functionally conserved in
      yeast, flies, and mammals. Fbw7 associates specifically with phosphorylated
      cyclin E, and SCFFbw7 catalyzes cyclin E ubiquitination in vitro. Depletion of
      Fbw7 leads to accumulation and stabilization of cyclin E in vivo in human and
      Drosophila melanogaster cells. Multiple F-box proteins contribute to cyclin E
      stability in yeast, suggesting an overlap in SCF E3 ligase specificity that
      allows combinatorial control of cyclin E degradation.

PMID- 11533446
TI  - College science: pass, no credit.

PMID- 11533447
TI  - Astronomy. Academy panel opposes U.S. funding shake-up.

PMID- 11533448
TI  - Stem cell lines. NIH's list of 64 leaves questions.

PMID- 11533449
TI  - Human subjects. Court rebukes Hopkins for lead paint study.

PMID- 11533450
TI  - Superconductivity. C60 enters the race for the top.

PMID- 11533451
TI  - Longevity. Hints of a 'master gene' for extreme old age.

PMID- 11533452
TI  - Dinosaur motion. Did saurian predators fold up on turns?

PMID- 11533453
TI  - Paleoecology. How grasses got the upper hand.

PMID- 11533454
TI  - Science on the Internet. Mysterious e-photos vex paleontologists.

PMID- 11533455
TI  - Intellectual property. Blue LED inventor sues former company.

PMID- 11533456
TI  - Drug pricing. NIH report knocks tax on blockbusters.

PMID- 11533457
TI  - Medicine. Rethinking a vaccine's risk.

PMID- 11533458
TI  - Structural biology. Brazil network sees the light.

PMID- 11533460
TI  - Meteoritics. A meteoriticist speaks out, his rocks remain mute.

PMID- 11533459
TI  - Ecology. Defending deadwood.

PMID- 11533461
TI  - Marco Baggiolini. Riding off into an alpine sunset--or sunrise.

PMID- 11533463
TI  - Global health. WHO ranking of health system performance.

PMID- 11533464
TI  - Photocatalysis. Fuel from photons.

PMID- 11533465
TI  - Surface science. Bridging gaps and opening windows.

PMID- 11533466
TI  - Biomedicine. Clotting factors build blood vessels.

PMID- 11533467
TI  - Social science and ecology. Networking tips for social scientists and ecologists.

PMID- 11533469
TI  - Reintroducing the intro course.

PMID- 11533470
TI  - Information overload hampers biology reforms.

PMID- 11533471
TI  - Reading, writing, and chemistry are potent mix.

PMID- 11533472
TI  - Making room for diversity makes sense.

PMID- 11533473
TI  - Europe seeks to harmonize its degrees.

PMID- 11533474
TI  - Student research: what is it good for?

PMID- 11533475
TI  - China broadens training for elite students.

PMID- 11533476
TI  - Other schools go first with narrower approach.

PMID- 11533478
TI  - MIT offers world-class courses, for free.

PMID- 11533477
TI  - Online, on campus: proceed with caution.

PMID- 11533479
TI  - Are we having fun yet? Joys and sorrows of learning online.

PMID- 11533480
TI  - Online science offerings are hard to reel in.

PMID- 11533481
TI  - Open university: a pioneer presses on.

PMID- 11533482
TI  - Online science is a stretch for Asia.

PMID- 11533483
TI  - Undergraduate research, graduate mentoring, and the university's mission.
AB  - Undergraduate research and graduate mentoring have received a great deal of
      attention in recent times. What do these activities have in common? They both
      speak to the primary mission of the research university, which is not merely
      carrying out research but training students to do research. The knowledge-based
      global economy, with its wealth of information and opportunities, has increased
      undergraduate students' need for research skills as well as graduate students'
      desire for personal guidance. As the research university matures, the boundaries
      between graduate and undergraduate education are blurring. Indeed, if we focus on
      the learning process, we find not two but five levels of learning at the research
      university: lower division, upper division, master's, doctoral, and postdoctoral.
      All five levels form a continuum, a series of gradual steps. The mission of the
      university is to introduce students to research, to inspire in them a passion for
      discovery at each of these levels.

PMID- 11533484
TI  - Spatiotemporal self-organization in a surface reaction: from the atomic to the
      mesoscopic scale.
AB  - Scanning tunneling microscopy data revealed the atomic processes in propagating
      reaction fronts that occur in the catalytic oxidation of hydrogen on Pt(111). The
      fronts were also characterized on mesoscopic length scales with respect to their
      velocity and width. Simulations on the basis of a reaction-diffusion model
      reproduce the experimental findings qualitatively well. The quantitative
      comparison reveals the limitations of this traditional approach to modeling
      spatiotemporal pattern formation in nonlinear dynamics.

PMID- 11533485
TI  - Hydrogen produced from hydrohalic acid solutions by a two-electron mixed-valence
      photocatalyst.
AB  - Energy conversion cycles are aimed at driving unfavorable, small-molecule
      activation reactions with a photon harnessed by a transition metal complex. A
      challenge that has occupied researchers for several decades is to create
      molecular photocatalysts to promote the production of hydrogen from homogeneous
      solution. We now report the use of a two-electron mixed-valence dirhodium
      compound to photocatalyze the reduction of hydrohalic acid to hydrogen. In this
      cycle, photons break two RhII-X bonds of a LRh0-RhIIX2 core in the presence of a
      halogen trap to regenerate the active LRh0-Rh0 catalyst, which reacts with
      hydrohalic acid to produce hydrogen.

PMID- 11533486
TI  - Design of bioelectronic interfaces by exploiting hinge-bending motions in
      proteins.
AB  - We report a flexible strategy for transducing ligand-binding events into
      electrochemical responses for a wide variety of proteins. The method exploits
      ligand-mediated hinge-bending motions, intrinsic to the bacterial periplasmic
      binding protein superfamily, to establish allosterically controlled interactions
      between electrode surfaces and redox-active, Ru(II)-labeled proteins. This
      approach allows the development of protein-based bioelectronic interfaces that
      respond to a diverse set of analytes. Families of these interfaces can be
      generated either by exploiting natural binding diversity within the superfamily
      or by reengineering the specificity of individual proteins. These proteins may
      have numerous medical, environmental, and defense applications.

PMID- 11533487
TI  - Seismic evidence for hotspot-induced buoyant flow beneath the Reykjanes Ridge.
AB  - Volcanic hotspots and mid-ocean ridge spreading centers are the surface
      expressions of upwelling in Earth's mantle convection system, and their
      interaction provides unique information on upwelling dynamics. I investigated the
      influence of the Iceland hotspot on the adjacent mid-Atlantic spreading center
      using phase-delay times of seismic surface waves, which show anomalous
      polarization anisotropy-a delay-time discrepancy between waves with different
      polarizations. This anisotropy implies that the hotspot induces buoyancy-driven
      upwelling in the mantle beneath the ridge.

PMID- 11533488
TI  - Climate change as the dominant control on glacial-interglacial variations in C3
      and C4 plant abundance.
AB  - Although C4 plant expansions have been recognized in the late Miocene,
      identification of the underlying causes is complicated by the uncertainties
      associated with estimates of ancient precipitation, temperature, and partial
      pressure of atmospheric carbon dioxide (PCO2). Here we report the carbon isotopic
      compositions of leaf wax n-alkanes in lake sediment cores from two sites in
      Mesoamerica that have experienced contrasting moisture variations since the last
      glacial maximum. Opposite isotopic trends obtained from these two sites indicate
      that regional climate exerts a strong control on the relative abundance of C3 and
      C4 plants and that in the absence of favorable moisture and temperature
      conditions, low PCO2 alone is insufficient to drive an expansion of C4 plants.

PMID- 11533489
TI  - Duration of nuclear NF-kappaB action regulated by reversible acetylation.
AB  - The nuclear expression and action of the nuclear factor kappa B (NF-kappaB)
      transcription factor requires signal-coupled phosphorylation and degradation of
      the IkappaB inhibitors, which normally bind and sequester this pleiotropically
      active factor in the cytoplasm. The subsequent molecular events that regulate the
      termination of nuclear NF-kappaB action remain poorly defined, although the
      activation of de novo IkappaBalpha gene expression by NF-kappaB likely plays a
      key role. Our studies now demonstrate that the RelA subunit of NF-kappaB is
      subject to inducible acetylation and that acetylated forms of RelA interact
      weakly, if at all, with IkappaBalpha. Acetylated RelA is subsequently
      deacetylated through a specific interaction with histone deacetylase 3 (HDAC3).
      This deacetylation reaction promotes effective binding to IkappaBalpha and leads
      in turn to IkappaBalpha-dependent nuclear export of the complex through a
      chromosomal region maintenance-1 (CRM-1)-dependent pathway. Deacetylation of RelA
      by HDAC3 thus acts as an intranuclear molecular switch that both controls the
      duration of the NF-kappaB transcriptional response and contributes to the
      replenishment of the depleted cytoplasmic pool of latent NF-kappaB-IkappaBalpha
      complexes.

PMID- 11533490
TI  - Allosteric activation of a spring-loaded natriuretic peptide receptor dimer by
      hormone.
AB  - Natriuretic peptides (NPs) are vasoactive cyclic-peptide hormones important in
      blood pressure regulation through interaction with natriuretic cell-surface
      receptors. We report the hormone-binding thermodynamics and crystal structures at
      2.9 and 2.0 angstroms, respectively, of the extracellular domain of the
      unliganded human NP receptor (NPR-C) and its complex with CNP, a 22-amino acid
      NP. A single CNP molecule is bound in the interface of an NPR-C dimer, resulting
      in asymmetric interactions between the hormone and the symmetrically related
      receptors. Hormone binding induces a 20 angstrom closure between the membrane
      proximal domains of the dimer. In each monomer, the opening of an interdomain
      cleft, which is tethered together by a linker peptide acting as a molecular
      spring, is likely a conserved allosteric trigger for intracellular signaling by
      the natriuretic receptor family.

PMID- 11533491
TI  - Regulation of Wnt signaling and embryo patterning by an extracellular sulfatase.
AB  - The developmental signaling functions of cell surface heparan sulfate
      proteoglycans (HSPGs) are dependent on their sulfation states. Here, we report
      the identification of QSulf1, the avian ortholog of an evolutionarily conserved
      protein family related to heparan-specific N-acetyl glucosamine sulfatases.
      QSulf1 expression is induced by Sonic hedgehog in myogenic somite progenitors in
      quail embryos and is required for the activation of MyoD, a Wnt-induced regulator
      of muscle specification. QSulf1 is localized on the cell surface and regulates
      heparan-dependent Wnt signaling in C2C12 myogenic progenitor cells through a
      mechanism that requires its catalytic activity, providing evidence that QSulf1
      regulates Wnt signaling through desulfation of cell surface HSPGs.

PMID- 11533492
TI  - A role for thrombin receptor signaling in endothelial cells during embryonic
      development.
AB  - The coagulation protease thrombin triggers fibrin formation, platelet activation,
      and other cellular responses at sites of tissue injury. We report a role for
      PAR1, a protease-activated G protein-coupled receptor for thrombin, in embryonic
      development. Approximately half of Par1-/- mouse embryos died at midgestation
      with bleeding from multiple sites. PAR1 is expressed in endothelial cells, and a
      PAR1 transgene driven by an endothelial-specific promoter prevented death of Par1
      /- embryos. Our results suggest that the coagulation cascade and PAR1 modulate
      endothelial cell function in developing blood vessels and that thrombin's actions
      on endothelial cells-rather than on platelets, mesenchymal cells, or fibrinogen
      contribute to vascular development and hemostasis in the mouse embryo.

PMID- 11533493
TI  - UDP-glucose dehydrogenase required for cardiac valve formation in zebrafish.
AB  - Cardiac valve formation is a complex process that involves cell signaling events
      between the myocardial and endocardial layers of the heart across an elaborate
      extracellular matrix. These signals lead to marked morphogenetic movements and
      transdifferentiation of the endocardial cells at chamber boundaries. Here we
      identify the genetic defect in zebrafish jekyll mutants, which are deficient in
      the initiation of heart valve formation. The jekyll mutation disrupts a homolog
      of Drosophila Sugarless, a uridine 5'-diphosphate (UDP)-glucose dehydrogenase
      required for heparan sulfate, chondroitin sulfate, and hyaluronic acid
      production. The atrioventricular border cells do not differentiate from their
      neighbors in jekyll mutants, suggesting that Jekyll is required in a cell
      signaling event that establishes a boundary between the atrium and ventricle.

PMID- 11533494
TI  - Reversal of obesity- and diet-induced insulin resistance with salicylates or
      targeted disruption of Ikkbeta.
AB  - We show that high doses of salicylates reverse hyperglycemia, hyperinsulinemia,
      and dyslipidemia in obese rodents by sensitizing insulin signaling. Activation or
      overexpression of the IkappaB kinase beta (IKKbeta) attenuated insulin signaling
      in cultured cells, whereas IKKbeta inhibition reversed insulin resistance. Thus,
      IKKbeta, rather than the cyclooxygenases, appears to be the relevant molecular
      target. Heterozygous deletion (Ikkbeta+/-) protected against the development of
      insulin resistance during high-fat feeding and in obese Lep(ob/ob) mice. These
      findings implicate an inflammatory process in the pathogenesis of insulin
      resistance in obesity and type 2 diabetes mellitus and identify the IKKbeta
      pathway as a target for insulin sensitization.

PMID- 11533495
TI  - Afterimage of perceptually filled-in surface.
AB  - An afterimage induced by prior adaptation to a visual stimulus is believed to be
      due to bleaching of photochemical pigments or neural adaptation in the retina. We
      report a type of afterimage that appears to require cortical adaptation. Fixating
      a neon-color spreading configuration led not only to negative afterimages
      corresponding to the inducers (local afterimages), but also to one corresponding
      to the perceptually filled-in surface during adaptation (global afterimage).
      These afterimages were mutually exclusive, undergoing monocular rivalry. The
      strength of the global afterimage correlated to a greater extent with perceptual
      filling-in during adaptation than with the strength of the local afterimages.
      Thus, global afterimages are not merely by-products of local afterimages, but
      involve adaptation at a cortical representation of surface.

PMID- 11533496
TI  - Acute outcome with the flexicut directional coronary atherectomy catheter for the
      treatment of coronary in-stent restenosis.
AB  - In-stent restenosis (ISR) is a growing problem that is without a practical,
      efficacious treatment strategy. The purpose of this study was to determine the
      acute outcome of 17 patients with coronary ISR who were treated with the new 8
      French (Fr), guide-catheter compatible Flexicut directional atherectomy catheter
      (Guidant Corporation, Santa Clara, California). Failure to deliver the device
      occurred in 2/17 ISR lesions. The remaining 15 ISR lesions were successfully
      debulked (e.g., minimum lumen diameter pre-procedure: 0.30 +/- 0.16 mm; post
      atherectomy plus adjuvant therapy: 2.16 +/- 0.57 mm). Of note, the reference
      vessel diameter was only 2.62 +/- 0.63 mm. In 11/15 tissue specimens, macroscopic
      or microscopic particles consistent with stent material were found. There was an
      absence of acute closure or elevations of creatinine phosphokinase levels. Apart
      from 1 patient who developed recurrent restenosis, all other patients
      demonstrated either clinical improvement or lack of restenosis during early
      clinical follow-up (mean, 5 months). We conclude that use of the Flexicut
      catheter provides satisfactory debulking and early clinical outcomes in patients
      with ISR. Long-term follow-up of these and additional patients will be helpful in
      determining the efficacy of the Flexicut atherectomy catheter for the treatment
      of ISR.

PMID- 11533497
TI  - Vascular complications after hemostatic puncture closure device (Angio-Seal) are
      not higher in overweight patients.
AB  - BACKGROUND: Angio-Seal (Daig Corporation, Minnetonka, Minnesota) allows earlier
      discharge from the hospital after coronary angiography. Manual compression in
      overweight patients after percutaneous procedures is associated with a higher
      incidence of groin complications. The purpose of this study was to determine if a
      vascular closure device could be safely used without increasing the risk of
      vascular complications in overweight patients. METHODS: A total of 198 patients
      who received the 6 French Angio-Seal device after diagnostic coronary angiography
      were divided into 3 groups. Group A included patients with a body mass index
      (BMI) of < or = 25, group B with BMI between 25 and 30, and group C with BMI > or
      = 30. Patients were followed for groin complications during their hospital stay.
      RESULTS: Complication rates were comparable between the 3 groups. Groin
      complications occurred in 11% in group A, 5% in group B and 6% in group C.
      CONCLUSION: After diagnostic cardiac catheterization, a vascular closure device
      such as Angio-Seal can be safely used in overweight patients.

PMID- 11533498
TI  - Angio-Seal in overweight patients: is Angio-Seal use safe in overweight patients
      or is it unsafe in lower-weight patients?

PMID- 11533499
TI  - Six-month results of small vessel stenting (2.0-2.8 mm) with the Biodivysio SV
      stent.
AB  - We report the 6-month follow-up results of our initial retrospective experience
      with the Biodivysio small vessel (SV) stent (Biocompatibles, Galway, United
      Kingdom) designed for 2.0-2.8 mm vessel diameters. This stent is manufactured
      with a smaller stainless-steel tube (1.0 mm) and is coated with
      phosphorylcholine. Procedural success was 95.7% and the major adverse cardiac
      events at 6 months were 20%. We conclude that the Biodivysio SV stent is a safe
      device that does not induce excessive acute thrombosis or early restenosis.

PMID- 11533500
TI  - Small vessel stenting: an intricate field!

PMID- 11533501
TI  - Clinical outcome of stent implantation in small coronary arteries using different
      types of coronary stents.
AB  - PURPOSE: We evaluated the results of stent placement in small coronary arteries.
      SUBJECTS: The subjects were divided into 2 groups: the first contained 911
      lesions treated with stenting in the coronary arteries (stent group), and the
      second contained 1,203 background- and patient-matched lesions treated with
      balloon angioplasty (POBA group). There was no significant difference in the
      background of patients or lesions between the groups. A "small coronary artery"
      was defined as a coronary artery with a reference vessel diameter < 3.0 mm.
      RESULTS: There was no significant difference in incidence of acute myocardial
      infarction (AMI), coronary artery bypass grafting, or death between the groups.
      In the stent group, acute occlusion (0.8%) and subacute thrombosis (2.1%)
      occurred. The restenosis rate of 29.8% in the stent group was significantly lower
      than in the POBA group (38.2%; p < 0.01). The restenosis rate of 19.4% in stented
      vessels 3.0 mm diameter was significantly lower than in vessels < 3.0 mm diameter
      (29.8%; p < 0.01). The rate of restenosis was 22.9% for the Multi-Link stent,
      24.4% for the NIR stent, 34.1% for the GFX stent, and 35.3% for the PS stent. The
      restenosis rate of 23.8% in stented vessels > 2.5 mm diameter and < or = 20 mm
      length was significantly lower than in vessels , < or = 2.5 mm diameter and > 20
      mm length (32.7%; p < 0.01). Factors associated with restenosis, analyzed using a
      stepwise multivariate logistic regression model, included ostial lesions and post
      procedural minimum lumen diameter. CONCLUSIONS: Stent implantation in vessels <
      3.0 mm diameter using a newly designed coronary stent yielded favorable clinical
      results, while there was a high prevalence of restenosis, leading to diffused
      stenotic lesions, in vessels < 2.5 mm diameter.

PMID- 11533502
TI  - Adjunctive therapies in the cath lab. Subacute stent thrombosis developing twelve
      days after discontinuation of ticlopidine treatment.
AB  - The two structurally related thienopyridines, ticlopidine and clopidogrel in
      addition to aspirin, have become the standard regimen for prevention of subacute
      thrombosis (SAT) after coronary stent implantation. Although both regimens are
      highly effective, ticlopidine suffers from severe hematologic side effects.
      Recent trials encourage shorter duration of therapy with these agents. However,
      the optimal duration of antiplatelet therapy after stenting is still not clear.
      We report a case of SAT developing 12 days after discontinuation of 2 weeks of
      aspirin plus ticlopidine therapy. We believe that the present data are still not
      clear regarding the optimum duration of antiplatelet therapy after stenting.

PMID- 11533503
TI  - Adjunctive therapies in the cath lab. Successful medical therapy of left main
      thrombosis: value of serial coronary angiography.
AB  - Acute coronary syndromes (ACS), including unstable angina, non-Q wave myocardial
      infarctions (MI) and Q-wave MIs, are usually the result of plaque rupture and
      subsequent thrombus formation. Commonly, patients with ACS have significant
      underlying coronary artery disease (CAD) demonstrable by coronary angiography and
      are candidates for prompt revascularization. In many cases, however, ACS are due
      to coronary thrombosis in the absence of obstructive CAD and therefore aggressive
      medical therapy may be sufficient. Coronary angiography is an invaluable resource
      for individualized treatment decisions. We describe a patient with thrombosis of
      the left main coronary artery successfully treated with aggressive and prolonged
      antiplatelet and anticoagulant therapy under the guidance of serial coronary
      angiography.

PMID- 11533504
TI  - Adjunctive therapies in the cath lab. Combination of tirofiban and alteplase in
      acute myocardial infarction.
AB  - Primary angioplasty results in higher reperfusion rates than fibrinolysis in
      patients with acute myocardial infarction (MI). Two recent trials have shown
      improved rates of reperfusion when a reduced-dose thrombolytic is combined with
      the platelet glycoprotein IIb/IIIa receptor inhibitor abciximab. We present a
      case report of acute MI successfully treated with a combination of tirofiban and
      half-dose alteplase and eventual percutaneous coronary intervention.

PMID- 11533505
TI  - Adjunctive therapies in the cath lab. Successful thrombolysis using the
      combination of tissue plasminogen activator and abciximab in an adult with
      Kawasaki's disease.
AB  - Kawasaki's disease is an acute systemic vasculitic syndrome that primarily
      affects children. Coronary aneurysms are common vasculitic sequelae of Kawasaki's
      disease. Intracoronary thrombosis and embolization are potential consequences of
      coronary aneurysms. We describe our experience of successful thrombolysis using
      the combination of reduced-dose intravenous tissue plasminogen activator and
      abciximab as described in the Thrombolysis in Myocardial Infarction 14 trial
      (TIMI 14) to treat a patient found to have intracoronary thrombus at the site of
      aneurysm formation due to Kawasaki's disease.

PMID- 11533506
TI  - Adjunctive therapies in the cath lab. Intracoronary tirofiban infusion in a case
      with massive intracoronary thrombus.
AB  - By inhibiting platelet aggregation, glycoprotein IIb/IIIa inhibitors prevent
      arterial occlusion and reduce ischemic complications in the setting of acute
      ischemic coronary syndromes associated with intracoronary thrombus. There are
      also accumulating data in the literature regarding the local use of these agents
      for thrombus dissolution. We report a case with massive right coronary artery
      thrombus in which the thrombus was successfully dissolved with intracoronary
      tirofiban infusion. To the best of our knowledge, this is the first case of this
      kind.

PMID- 11533507
TI  - Adjunctive therapies in the cath lab. Use of combination glycoprotein IIb/IIIa
      inhibitor and direct thrombin inhibitor drugs to support percutaneous coronary
      stent placement in a patient with renal insufficiency and heparin-induced
      thrombocytopenia.
AB  - An 81-year-old woman with a history of prior coronary artery bypass surgery,
      heparin-induced thrombocytopenia with "white clot" syndrome, and renal
      insufficiency presented with unstable angina. She was referred for cardiac
      catheterization. Complex percutaneous revascularization of the native circumflex
      coronary artery was performed using stents. A combination of tirofiban and
      lepirudin was used with dosing adjusted for renal insufficiency. The hospital
      course was uncomplicated and the patient was discharged on the fourth hospital
      day. This is only the second report of the combination use of direct thrombin
      inhibitor and glycoprotein IIb/IIIa receptor inhibitor.

PMID- 11533508
TI  - Financing options for clinical practices.

PMID- 11533509
TI  - Street smarts.

PMID- 11533510
TI  - Saphenous vein graft disease: a left main equivalent.

PMID- 11533511
TI  - Roots of Concern with Nonhuman Animals in Biomedical Ethics.

PMID- 11533512
TI  - Bioethics, Animal Research, and Ethical Theory.

PMID- 11533513
TI  - Nonhuman Primate Models of Visually Based Cognition.

PMID- 11533514
TI  - Transgenic Animal Models for the Study of Inherited Retinal Dystrophies.

PMID- 11533515
TI  - Use of Animal Models in the Study of Inflammatory Mediators of Pneumonia.

PMID- 11533516
TI  - Thromboembolism and pregnancy.

PMID- 11533518
TI  - The intima media thickness and coronary risk factors.
AB  - BACKGROUND:  AIM: to estimate the degree of atherosclerosis in the carotids with
      different measurements of the intima media thickness (IMT), obtained by
      ultrasound and to analyze the correlations of these measures to coronary risk
      factors. METHODS:  DESIGN AND PARTICIPANTS: 130 employed men and women
      volunteered after public announcement. MEASURES: Health and life-style were
      charted using a comprehensive questionnaire. Anthropometric measurements, and
      blood pressure after 10 min of rest were obtained at clinical examination. Blood
      tests included analyses for fibrinogen, cholesterol, and HDL-cholesterol. The IMT
      was measured bilaterally three times at the transition of a. carotis to bulbus as
      well as on a. carotis 0.5 cm proximal thereto. Analyses were conducted with four
      methodologically different ways of expressing IMT as the dependent variable:
      IMT(left), IMT(communis), IMT(mean) and IMT(max). RESULTS: Among the measurements
      of IMT, IMT(max) showed the strongest correlations to coronary risk factors,
      significantly associated with sex and age. In univariate analyses only the degree
      of physical activity in the leisure time correlated significantly to IMT(max)
      among men. When adjusted for age, HDL-cholesterol, BMI, systolic blood pressure
      and physical activity in leisure time in a multiple linear regression analysis
      IMT(max) showed significant correlations to physical activity in leisure time and
      systolic blood pressure among men older than 45 years. Among women IMT(max) was
      significantly correlated to HDL-cholesterol (inversely), which remained
      significant in the multiple regression analysis including the same factors as for
      men. CONCLUSIONS: IMT(max) among four measures of IMT showed the strongest
      associations to coronary risk factors in otherwise healthy individuals.

PMID- 11533517
TI  - Brain CT infarction in patients with carotid atheroma. Does it predict a future
      event?
AB  - BACKGROUND: The aim of the present study was to investigate the predictive value
      for subsequent stroke of different patterns of brain CT infarction in patients
      with carotid atheroma. METHODS: Prospective study on 138 patients, with 138
      carotid plaques, having, on presentation, a greater than 50 percent stenosis on
      duplex scanning and associated with an ipsilateral (to the plaque) amaurosis
      fugax (AF), hemispheric transient ischaemic attack (HTIA) or which were
      asymptomatic. This carotid artery defined the side of interest. All patients had
      a brain CT scan on presentation and subsequently were followed for a period of 1
      5 years (mean 3.14). The baseline CT neurovascular findings on the side of
      interest were classified as pattern A (discrete subcortical and cortical
      infarctions), pattern B (haemodynamic infarctions, widespread white matter
      lesions, basal ganglia infarctions and lacunae) and normal CT. RESULTS: On follow
      up, 5/27 (18.5 percent) of patients with pattern A, 4/38 (10.5 percent) with
      pattern B and 3/73 (4.1 percent) with normal CT appearance developed stroke in
      the hemisphere of interest (Cox regression: p=0.02). CONCLUSIONS: Pattern A
      confers an unfavourable prognosis in patients with carotid atheroma who are
      either asymptomatic or presented with amaurosis fugax or hemispheric transient
      ischaemic attacks.

PMID- 11533519
TI  - Effects of buflomedil on early carotid atherosclerosis in Type 2 diabetic
      patients.
AB  - BACKGROUND: An increased thickness of the carotid artery wall is thought to be a
      sign of early atherosclerosis. We have investigated the effect of early treatment
      with buflomedil on the prevention of the arterial wall thickening. METHODS:
      Eighty patients with Type 2 diabetes were studied. Oral buflomedil (600 mg once
      daily) was administered for 12 months in 42 patients randomly selected, while 38
      received no treatment. The two groups were matched for age, sex, body mass index
      (BMI), duration of diabetes and glycaemic control. Arterial wall thickness was
      measured as the mean of the maximum intima media thickness (IMT) in 8 carotid
      segments measured by B-mode ultrasound. RESULTS: Blood pressure and lipid levels
      remained unchanged in the two studied groups while no difference was found in
      metabolic control between them. The IMT increase over 12 months was 0.04 mm in
      the buflomedil group whereas in that without buflomedil it was 0.10 mm.
      CONCLUSIONS: We conclude that buflomedil treatment may be useful in decreasing
      the progression rate of arterial wall thickness.

PMID- 11533520
TI  - Oxidative stress during peripheral angioplasty. Implication for late restenosis?
AB  - BACKGROUND: Percutaneous transluminal angioplasty (PTA) is routine treatment for
      patients with peripheral arterial disease (PAD). The procedure induces local
      generation of reactive oxygen species (ROS), such as H2O2. Since these have been
      shown to stimulate vascular smooth muscle cell growth (VSMCG), we investigated
      peroxide levels in patients with PAD during PTA and related these results to late
      clinical outcome. METHODS: Thirty patients (17 male, 13 female, 20 Fontain stage
      II, 10 Fontaine stage IV, median age 68 years) undergoing PTA of a 2-6 cm
      stenosis of the femoral or popliteal artery were included. The procedure was
      performed successfully in all patients. At follow-up six months thereafter
      restenosis was evaluated by duplex sonography. Total peroxide concentrations were
      determined in plasma drawn before, 6, 24 and 48 hours after the procedure by the
      Operoxide activityO assay, which is based on the reaction of horseradish
      peroxidase with plasma peroxides, using tetramethylbenzidine as the chromogenic
      substrate. RESULTS: The median peroxide level before angioplasty was 280 mmol/L
      (range 47-549). Levels were higher in patients with advanced disease, in smokers
      and in patients with diabetes. In response to angioplasty, peroxide levels
      increased within 48 hours (p<0.001). Six months after the procedure, restenosis
      was observed in 10/30 (33 percent) of patients. Clinical outcome was not
      dependent upon baseline or postinterventional peroxide levels. CONCLUSIONS:
      Elevated peroxide levels are seen in patients with advanced arteriosclerotic
      disease and in those with diabetes, but are not predictive for late restenosis.

PMID- 11533521
TI  - Oxygen-free radical decrease in hypertensive patients treated with lercanidipine.
AB  - BACKGROUND: The relationship between oxidative stress, lipoproteins,
      cardiovascular risk factors and vascular disease progression has recently
      attracted fresh attention due to the possibility of measuring free radicals
      (FRs). The aim of this study was to evaluate blood plasma variations in oxygen
      FRs in hypertensive patients treated with lercanidipine, a drug acting on blood
      pressure and microcirculation. METHODS: Twenty-two patients with moderate
      hypertension (M:F=12:10; age=52) and no vascular disease (evaluated by high
      resolution ultrasound) were treated for 24 weeks with Lercanidipine (10 mg/day or
      20 mg/day if BP values did not decrease at least 15 percent after four weeks of
      treatment). BP was measured at inclusion and after 4, 8, 12 and 24 weeks of
      treatment. FRs measurements (using the D-Roms test) were made at inclusion, at
      the 8th, 12th and 24th week. RESULTS: All patients completed the treatment which
      was well tolerated and without side effects. Systolic and diastolic BP decreased
      after 8, 12 (p<0.05) and 24 weeks (at 24 weeks systolic pressure was decreased by
      21.1 percent, and diastolic by 11.1 percent; p<0.02). FRs levels progressively
      decreased from 541 Carr Units (SD 54) at inclusion to 411 (SD 56) at eight weeks
      (p<0.05), to 401 (SD 35) (p<0.05) at 12 weeks and finally to 398 (SD 33),
      (p<0.02) at 24 weeks of treatment (72.2 percent of the initial value).
      CONCLUSIONS: The possibility of measuring FRs in vivo with a simple, inexpensive
      test allows the identification of subjects with a high level of oxidative stress,
      and the monitoring of the effects of treatments. Lercanidipine, acting on blood
      pressure, on the microcirculation and decreasing oxidative stress and Frs plasma
      levels may effectively decrease the rate of progression of cardiovascular
      diseases offering the advantage of an increased level of protection in patients
      with high levels of oxidative stress.

PMID- 11533522
TI  - An audit of the clinical and sub-clinical changes in the first year following an
      acute deep vein thrombosis.
AB  - BACKGROUND: An audit of 100 proximal (above knee) deep vein thromboses (DVT) was
      carried out to document the dynamic status of the condition during the first
      year. METHODS: Duplex ultrasound was used to diagnose the presence of an acute
      deep vein thrombosis in a consecutive series of patients. Follow-up bilateral
      ultrasound scans were performed at one week, one month, six months and at one
      year and clot retraction, lysis or extension were recorded. The patients'
      treatment regime and symptoms were also recorded at each follow-up examination.
      RESULTS: There were 100 proximal DVT's from 89 patients (11 bilateral
      thromboses). The patient population included those with a previous history of DVT
      or in the end stages of a major illness and those with reversible risk factors.
      The mortality rate over the one-year period was 14 percent, most of the deaths
      occurring in the first month. The majority of deaths occurred as a result of an
      underlying primary disease (e.g. cancer) and 3 percent died from a pulmonary
      embolism. All patients were treated initially with either intravenous (IV)
      heparin or subcutaneous low molecular weight (SCLMW) heparin. Following heparin
      all patients were treated with warfarin. The duration of anticoagulant therapy
      varied with most physicians treating the patient for six months. Symptomatic and
      asymptomatic events (pulmonary emboli, extension of thrombi, new DVT's) were
      recorded in the follow-up period especially in the initial and late phase.
      CONCLUSIONS: The audit concluded that the diagnosis and treatment of DVT
      continues to be a major clinical problem with uncertainty as to the type and
      length of treatment required. The mobility of the patient was not considered in
      the choice of initial heparin treatment. Anticoagulants were generally continued
      for a period of up to six months regardless of the patient's risk factors. Little
      consideration was given to asymptomatic events with physicians still depending on
      unreliable clinical symptoms to determine if recurrences had occurred. Generally,
      no consideration was given to the long-term consequences of a post-thrombotic
      limb at the initial stage of treatment of a DVT.

PMID- 11533523
TI  - The PlA1/A2 polymorphism of platelet glycoprotein IIIa is not associated with
      deep venous thrombosis.
AB  - BACKGROUND: Platelet glycoprotein (GP) IIb/IIIa, a fibrinogen and von Willebrand
      factor binding membrane receptor, has an important role in platelet aggregation.
      A common leucine33-proline polymorphism (PlA1/A2) of the gene encoding the GP
      IIIa subunit is associated with platelet reactivity and has been proposed as a
      risk factor for atherothrombotic disease. The aim of this study was to
      investigate the role of this polymorphism for deep venous thrombosis (DVT).
      METHODS: We performed a case-control study including 206 patients with documented
      DVT and a sex- and age-matched group of 310 control subjects. GP IIIa genotypes
      were determined by restriction fragment analysis of amplimers containing the
      polymorphic site. RESULTS: A1/A1, A1/A2 and A2/A2 genotypes were found in 67.0,
      31.6 and 1.5 percent of patients and 72.3, 25.8 and 1.9 percent of controls
      (p=0.35), PlA2 allele frequencies were 0.17 in patients and 0.15 in controls
      (p=0.92). Odds ratio of the PlA2 allele for DVT was 1.21 (95 percent CI 0.85
      1.71, p=0.29) and remained insignificant after adjustment for factor V Leiden and
      prothrombin 20210A genotypes (1.22, 95 percent CI 0.86-1.75, p=0.27).
      CONCLUSIONS: Our data suggest that the PlA1/A2 polymorphism of GP IIIa is not
      associated with DVT.

PMID- 11533524
TI  - Risk factors of atherosclerosis and saphenous vein endothelial function.
AB  - BACKGROUND: Impaired vasomotor function has been suggested as playing a role in
      the pathophysiology of atherosclerosis and it may also affect the late patency of
      bypass grafts. We evaluated, in vitro, the influence of risk factors of
      atherosclerosis on saphenous vein endothelial function in patients with
      cardiovascular diseases. METHODS: Forty-five saphenous vein rings with intact
      (E+) and denuded endothelium (E-) were studied. The following drugs were used:
      norepinephrine (NE), acetylcholine (Ach), histamine (H) and serotonine (5-HT).
      RESULTS: Contraction to norepinephrine (n=15) showed a maximal tension of 783+/
      115 percent that was increased in diabetics, smokers, and patients with
      hypertension. There was a wide range of response to acetylcholine in rings with
      intact endothelium (n=25), (mean relaxation 16.4+/-1.7 percent, ranging from 
      22.2 percent to 45 percent) with relaxation (26+/-1.1 percent) and contraction (
      11+/-1.2 percent); relaxation was reduced in patients with hypertension and in
      diabetics (7.4+/-2.6 percent vs non diabetics 24.4+/-1.73 percent; p<0.01). Five
      of the 12 veins from diabetics exibited contraction (10+/-1.48 percent).
      Histamine (n=15) caused moderate relaxation at low doses (25+/-2.46 percent)
      followed by contraction at higher concentrations (184+/-5.7 percent). This was
      greater in diabetics (193+/-6.8 percent vs non diabetics 157+/-5.3 percent;
      p=0.045) while in preparations without endothelium (n=10) only relaxation was
      obtained (45+/-2.89 percent). Contraction (242+/-7.4 percent) was observed in
      response to serotonine (n=15) that was not affected by endothelial removal. In
      this study saphenous vein: (1) exhibited a wide range of responses to
      acetylcholine; (2) evoked marked contraction to norepinephrine and serotonine;
      (3) elicited contraction in response to histamine that was endothelium-dependent,
      suggesting the production or the release of an endothelium-derived-contracting
      factor (EDCF). CONCLUSIONS: Saphenous vein is able to secrete a contracting
      factor in patients with risk factors of atherosclerosis and above all diabetes.
      The mechanisms that regulate the balance between the relaxing and contracting
      factors and how the endothelial cells become the source of the substances with
      vasoconstrictor activity remain to be determined.

PMID- 11533525
TI  - The in vitro effect of a low molecular weight heparin, nadroparin (Fraxiparine),
      on leukocytes obtained from patients with vascular diseases.
AB  - BACKGROUND: Both lymphocytes and granulocytes may play a role in the immune
      system-mediated inflammatory response associated with non-Q wave infarction and
      aortic aneurysms. METHODS: The purpose of this study was to establish the in
      vitro effects of a low molecular weight heparin (LMWH), nadroparin (Fraxiparine),
      on some functional parameters of peripheral granulocytes and lymphocytes isolated
      from control subjects and patients with aortic aneurysm or non-Q wave infarction.
      RESULTS: Nadroparin (0.06-600 AXaU/ml) exerted different in vitro effects on
      granulocytes and lymphocytes isolated from normal subjects and the patient
      groups. The following indices were assessed: superoxide anion release, lymphocyte
      proliferation, phagocytic activity and the cellular respiratory burst. The
      effects of nadroparin varied according to the patient group and the index of
      lymphocyte/granulocyte assessed. CONCLUSIONS: Since peripheral granulocytes
      isolated from these patients are activated, the observed inhibition exerted by
      nadroparin on superoxide anion release may be beneficial. LMWHs have additional
      effects that are independent of their anticoagulant activity. These effects may
      influence the "inflammatory component" of the atherosclerotic process.

PMID- 11533526
TI  - The effect of pretreatment with ischaemic preconditioning or cromakalim on
      perfusion in skeletal muscle during ischaemia-reperfusion injury.
AB  - BACKGROUND: Ischaemia-induced damage of skeletal muscle may lead to side effects
      in orthopaedic and reconstructive surgery where tourniquet ischaemia is applied
      to ensure a bloodless operative field. In this study we investigated the effect
      of ischaemia-reperfusion injury with and without preconditioning by studying the
      skeletal muscle microcirculation. A further aim was to establish whether
      ischaemic preconditioning or pretreatment with cromakalim, a potassium channel
      opener reduces ischaemia-reperfusion injury. METHODS: Twenty-eight Wistar rats
      were randomised into four groups (n=7 per group). Group 1, control with no
      treatment; Group 2, two and a half hours tourniquet ischaemia followed by two
      hours of reperfusion to the left hindlimb. Furthermore, we pre-treated two groups
      prior to the ischaemia-reperfusion period; Group 3 with three short cycles of
      ischaemia-reperfusion (5'/5') and Group 4 pre treated with cromakalim (100
      microg/kg bw). We monitored the gastrocnemius muscle blood flow in vivo. RESULTS:
      There were no significant changes in the skeletal muscle microcirculation and
      temperature at the baseline in the four groups (p=0.110). In the ischaemic
      reperfusion, ischaemia preconditioning and cromakalim groups, the recorded
      skeletal muscle microcirculation during ischaemia decreased significantly
      (p<0.001) with respect to the baseline. In Group 2 the microcirculation recovered
      rapidly after release of the tourniquet, but was significantly lower (37 percent
      of baseline value, p<0.001) within two hours of reperfusion. In the ischaemia
      preconditioning group the microcirculation as in the ischaemia-reperfusion group
      recovered rapidly after release of the tourniquet, although failing to reach the
      baseline value within two hours of reperfusion. The mean microcirculation value
      of the left limb was slightly higher than Group 2 but significantly lower
      compared to the baseline after two hours of reperfusion (p<0.001). The change in
      the skeletal muscle microcirculation with cromakalim after two hours of
      reperfusion was not significant when compared to baseline values (p>0.05). The
      cromakalim group after two hours reperfusion had significantly higher
      microcirculation values when compared with Groups 2 and 3 (p<0.001). During
      ischaemia-reperfusion in Groups 2-4, there was no significant alteration in the
      systemic haemodynamic circulation. CONCLUSIONS: This study supports the
      hypothesis that cromakalim reduces postischaemic skeletal muscle damage and
      reperfusion injury.

PMID- 11533527
TI  - Phenylephrine induced aortic vasoconstriction is attenuated in hyperthyroid rats.
AB  - BACKGROUND: Abnormal vascular responsiveness to vasoconstrictors may play an
      important role in peripheral vascular resistance in hyperthyroidism. The aim of
      the present study was to evaluate whether the vascular response to potassium
      chloride and phenylephrine is abnormal in a rat model of thyroxine-induced
      cardiac hypertrophy. METHODS: Left ventricular hypertrophy was induced in Wistar
      rats by subcutaneous administration of L-thyroxine for two weeks ("THYR"), n=17.
      Animals treated with normal saline served as controls, ("NORM"), n=20. The
      thoracic aorta was dissected and cut into rings that were suspended in an
      isolated organ bath with Krebs-Henseleit buffer. Maximal tension, Tmax, in g was
      measured in response to KCl and PE at the highest concentration in rings with
      endothelium (+E) and without endothelium (-E) in both groups. Relaxation response
      (Relax percent) to acetylcholine administration was expressed as percent of the
      maximal tension induced by phenylephrine. RESULTS: Left ventricular weight was
      0.9 (SEM, 0.04) g for THYR group vs 0.7 (0.02) g for the NORM group, p<0.05. With
      KCl, Tmax was not different between the THYR and NORM groups with and without
      endothelium. With PE, there was a difference in Tmax between THYR+E and NORM+E,
      1.2 (0.05) g vs 1.5 (0.09) g, p<0.05. Tmax was also different between THYR-E and
      NORM-E, 1.5 (0.08) g vs 1.7 (0.07) g, p<0.05. Relax percent was not significantly
      different between THYR+E and NORM+E (45.9 percent vs 42.8 percent, p>0.05).
      CONCLUSIONS: We conclude that: a) Vascular tension of the thoracic aorta in
      response to PE is lower in thyroxine-treated rats as compared to controls,
      probably due to enhanced PE-induced vasorelaxation at high concentration. b)
      Relaxation response of the thoracic aorta to acetylcholine is not different
      between THYR and NORM groups.

PMID- 11533528
TI  - Ruptured internal iliac artery aneurysm mimicking a hip fracture.
AB  - Internal iliac artery aneurysms are difficult to detect due to their wide range
      of clinical presentations. The mortality rate from ruptured internal aortic
      aneurysms is particularly high in part because of delayed diagnosis. This report
      reviews the management of a patient with a ruptured internal iliac artery
      aneurysm which presented mimicking a hip fracture.

PMID- 11533529
TI  - A comparative evaluation of effectiveness of medical and surgical therapy in
      patients with macroprolactinoma.
AB  - BACKGROUND: The surgical success rate in macroprolactinomas is quite low, while
      medical treatment is more effective in reducing PRL levels and tumour mass. In
      this study the effectiveness of surgical, medical and radiant approaches on
      clinical symptoms, PRL levels and tumour size were compared in a large series of
      patients with macroprolactinomas. METHODS: One hundred and thirty-two patients
      (63 males and 69 females) were followed-up. Eighty-three patients were operated
      by trans-sphenoidal (TSS) approach: 18 underwent only TSS, 10 were operated and
      then irradiated; 30 patients underwent TSS and dopamine agonists, 25 were treated
      by TSS, radiotherapy and dopamine agonists. One hundred and four patients were
      treated by medical therapy: 49 patients were only administered dopamine agonists
      and 55 were given dopamine agonists after unsuccessful surgery and/or
      radiotherapy. RESULTS: In 83 patients serum PRL levels decreased from 1873+/
      319.9 ng/ml to 831.6+/-297.8 ng/ml after trans-sphenoidal surgery: a significant
      PRL reduction was obtained in 18 cases (22%) and a full PRL normalization was
      found in 15 patients (18%). The pituitary adenoma was completely removed in the
      15 cases, in whom serum PRL normalized. Sexual function was restored in 57
      percent; of women and in 29 percent; of men. In contrast, dopaminergic drugs
      normalized PRL levels (from 1590.5+/-232.7 to 19.2+/-4.8 ng/ml) in 93/104
      patients (89 percent;). Sexual function was restored in 74 percent; of women and
      in 75 percent; of men. Radiotherapy, performed after unsuccessful TSS, was
      ineffective in normalizing PRL levels. CONCLUSIONS: Medical therapy should be
      considered the first choice treatment in macroprolactinomas, while the surgical
      approach is recommended when neurological compressive symptoms are present and in
      patients resistant or intolerant to dopamine agonists. Radiotherapy may be
      indicated only in the patients in whom medical and surgical therapy have not been
      successful.

PMID- 11533531
TI  - Clinical evaluation of thallium-201 single photon emission computed tomography in
      equivocal neuroradiological supratentorial lesions.
AB  - BACKGROUND: We performed cerebral 201Tl SPECT study on 38 presurgical patients
      with equivocal neuroradiological supratentorial lesions to detect differences in
      201Tl uptake index between tumor/non-tumor and high-grade/low-grade samples.
      METHODS: Authors identified 38 cases with presurgical equivocal neuroradiological
      supratentorial mass lesions. All cases were submitted to histological
      confirmation of the lesion by biopsy, sub-total or gross-total removal of the
      tumor. Between 23 patients suffering from gliomas, 13 were histologically
      classified as being of low-grade malignant tumors and 10 were classified as being
      of high-grade malignancy. Fifteen non-tumor histopathological specimens were also
      detected. The 201Tl index was defined as the ratio of average counts per pixel in
      the lesion to these in the opposite region. Analysis of variance (ANOVA) and
      unpaired Student's OtO-test statistical methods were applied. Actuarial survival
      time from the date of diagnosis was calculated using the Kaplan-Meier method.
      Follow-up evaluation and survival time were obtained through referring
      physicians. Cerebral CT or MR images were obtained every three months after
      discharged, or more often if indicated. RESULTS: Results showed that the 201Tl
      uptake index ranged from 1.10 to 3.00 in the tumors lesions (mean+/-SD: 1.68+/
      0.51) and from 0.80 to 1.40 in the non-tumors lesions (mean+/-SD: 1.07+/-0.17),
      (alpha < 0.0006 percent;). The 201Tl uptake index ranged from 1.10 to 2.30 in 13
      patients with low-grade tumors (mean+/-SD: 1.45+/-0.34) and from 1.30 to 3.00 in
      10 patients with high-grade tumors (mean+/-SD: 1.98+/-0.55), (alpha < 0.5
      percent;). CONCLUSIONS: Our results demonstrate the clinical utility of 201Tl
      brain SPECT to differentiate equivocal neuroradiological supratentorial lesions
      and to correlate relationship between preoperative diagnosis, histological tumor
      grade and prognosis.

PMID- 11533530
TI  - Hyperprolactinaemia and prolactin binding in benign intracranial tumours.
AB  - BACKGROUND: Meningiomas have been found to have receptors for several hormones,
      such as oestrogen, progesterone, somatostatin, dopamine and recently also for
      prolactin. METHODS: To investigate any possible role of prolactin in the growth
      of those tumours we detected the presence of prolactin-receptors (PRL-R) in 22
      meningiomas and we correlated these data with PRL serum levels in patients before
      surgery. We also studied 13 patients with schwannomas and 7 with other cerebral
      tumours (4 glioblastomas, 2 ependymomas and 1 astrocytoma). RESULTS: Increased
      prolactin binding was present in 10 (45.4 percent;) meningiomas, 9 (69.2
      percent;) schwannomas and in the patient with astrocytoma. The presence of high
      PRL levels was present in 6 (27.2 percent;) patients with meningiomas, 8 (61.5
      percent;) with schwannomas and in 3 (42.8 percent;) with other tumours. No direct
      correlation was present between serum PRL levels and PRL binding in all groups.
      CONCLUSIONS: In conclusion we confirmed the presence of PRL receptors in patients
      with meningiomas and we have also shown the presence of PRL receptors also in
      schwannomas. Moreover increased serum PRL were shown in some patients with
      different tumours of nervous tissue before surgery. Our data could suggest that
      PRL might have a role in the growth of meningiomas and schwannomas.

PMID- 11533532
TI  - Surgical treatment of moyamoya disease in pediatric age.
AB  - BACKGROUND: Moyamoya is a progressive occlusive cerebrovascular disease which
      affects the distal internal carotid artery and its main branches, and is
      characterized, from a clinical point of view, by a variety of ischemic
      manifestations ranging from transient ischemic attacks (TIA) to stroke. Although
      considered until recently as almost specific of Japanese population, it can also
      affect individuals of different origin, and there is an increasing interest for
      this rare disease in Western medical literature. Nonetheless papers dealing with
      moyamoya disease in pediatric age are still very rare and almost exclusively
      limited to isolated case reports. These considerations prompted us to review our
      experience with the diagnosis and treatment of such unusual disease. METHODS:
      Nine children (seven months to nine years of age) presented with clinical
      manifestations of occlusive cerebrovascular disease (TIAs or stroke), epilepsy,
      and/or psychomotor retardation. Neuroradiological investigation, and in
      particular cerebral angiography, demonstrated the classical pattern of moyamoya
      disease. Eight of these children underwent cerebral revascularization utilizing
      the encephalomyosynangiosis (EMS) technique, with a total of 14 operations (six
      on both sides, two on one side). RESULTS: There was no mortality neither major
      morbidity related to surgery. One patient with renovascular hypertension, died at
      home approximately six months after a successful operation, probably from
      cerebral hemorrhage. In all the cases postoperative angiography revealed a marked
      improvement in cerebral circulation. However, in spite of the apparently
      normalized cerebral blood flow, clinical manifestations were affected less
      significantly. In fact, there was only minimal if any improvement in children
      operated on with an already established hemiplegia; whereas improvement in motor
      ability was obtained in those presenting with hemiparesis or TIAs, as well as in
      epilepsy and psychomotor retardation. CONCLUSIONS: On the grounds of our results
      we conclude that cerebral revascularization (by means of a simple operation like
      the EMS) in children with moyamoya disease is worthwhile, provided that the
      operation be performed before irreversible cerebral damage is established;
      however, even under these circumstances the operation can at least stop the
      progression of the disease.

PMID- 11533534
TI  - Acute interhemispheric subdural hematomas. Report of nine cases.
AB  - Nine male patients with acute interhemispheric subdural hematoma (ISH) are
      presented. The etiologic factor was trauma for all patients (traffic accident and
      falling down). The young adult cases and one child had bad prognosis due to
      severe clinical findings and high mortality. The asymptomatic patients were
      treated conservatively. In this report, we discussed etiologic factors,
      presentation of age groups, whether an ISH progresses to a chronic convexity
      subdural hematoma (SH), and real mortality rates for ISH with relevant literature
      knowledge. As a result, ISHs can present in all age groups including shaken
      babies, severely injured young adults as well as low velocity trauma striken
      elderly patients (especially those under anticoagulant medication). We believe
      that an acute ISH does not change to chronic convexity SH; in fact they present
      as simultaneous acute thin convexity SH and acute ISH. It is also concluded that
      in contrast to previous literature ISH and acute SH patients of similar
      neurological status have similar mortality rates.

PMID- 11533533
TI  - Neuroendoscopic approach to complex hydrocephalus. Personal experience and
      preliminary report.
AB  - BACKGROUND: Neuroendoscopic premammilary third-ventriculocisternostomy in non
      communicating hydrocephalus represents, to date, the less invasive and effective
      procedure, whereas the neuroendoscopic approach to complex-hydrocephalus is
      limited to several small anecdotal series. METHODS: Among 57 pediatric patients
      affected by obstructive hydrocephalus, ranging in age from prenatal diagnosis to
      3 years (mean 1.2 year+/-11 months) and recruited over a 2-year period, we
      identified 11 cases with presurgical neuroradiological complex-hydrocephalus, at
      admission to our Department. In two cases Magnetic Resonance imaging showed
      bilateral atresic foramen of Monro and corpus callosum agenesya. In these cases
      an extracranial cerebrospinal fluid shunt device was implanted. The authors
      report retrospectively, the personal experience on a series of 9 pediatric
      patients with complex-hydrocephalus, such as multishunted (4 cases),
      multiloculated hydrocephalus (3 cases), and multiple ventricular cysts plus
      hydrocephalus (2 cases), in which a neuroendoscopic approach was performed. At
      admission, symptoms and signs of an increased intracranial pressure were presents
      in all cases. Follow-up ranged from 3 months to 2 years. In 8 cases third
      ventriculostomy was successfully performed whereas, in one case, the endoscopic
      procedure, in a patient younger than 1 month, was aborted and an extracranial
      cerebrospinal fluid device was implanted. RESULTS: In the postoperative period
      and during follow-up, a symptomatic relief and clinical improvement of
      preoperative signs and symptoms of increased intracranial pressure was seen in
      all cases. Nevertheless, in two patients psychomotor retardation worsened,
      respectively 6 and 7 months after the endoscopic procedure and then, an
      additional extracranial cerebrospinal fluid shunt device was implanted.
      CONCLUSIONS: In our selected cases of complex-hydrocephalus, the neuroendoscopic
      approach did not fail to determine clinical improvement after the first
      procedure, in spite of increased technical difficulties and minimum decreases of
      ventricular volume in postoperative images.

PMID- 11533535
TI  - Giant temporo-occipital sinus pericranii. A case report.
AB  - A rare case of a giant, temporo-occipital sinus pericranii is presented. A 38
      year-old male presented with minor symptoms of headache and heaviness over an
      enlarging temporo-occipital bone defect. Within the defect a soft, compressible,
      mass lesion was observed, which varied in size with changes in intracranial
      pressure. Radiological imaging demonstrated bone erosion around a fluid filled
      mass, which on angiography communicated via a series of channels with the
      transverse sinus. A diagnosis of sinus pericranii was made. Due to the risk of
      future complication the patient elected to undergo surgery, which successfully
      resected the mass and obliterated the venous communications with the diploic
      veins and transverse sinus. The classification, aetiology, differential
      diagnosis, radiological characteristics and management options relating to sinus
      pericranii are discussed.

PMID- 11533536
TI  - Trigeminal pain caused by a cerebellopontine-angle lipoma. Case report and review
      of the literature.
AB  - A 16-year-old girl complained of 2-year history of right facial pain, episodic
      vertigo and progressive hearing loss in the right ear. The facial pain was
      described as an episodic lancinating event confined to the second and third
      branch of the right trigeminal nerve. Computed tomography and magnetic resonance
      imaging revealed a 2 cm lesion in the right cerebellopontine-angle. At surgery, a
      soft, yellowish mass was found incorporating the 7th and 8th cranial nerves. The
      anterior-inferior cerebellar artery (AICA) was displaced medially and pushed into
      the sensory portion of the trigeminal nerve root, causing vascular compression.
      The hearing loss remained unchanged. The trigeminal pain disappeared over a
      period of several weeks. Patients can be harmed in an attempt to remove these
      neurovascular nonmalignant, generally non growing, fatty vascular lumps. Only a
      partial, meticulous removal should be performed with a maximum effort to
      decompress the affected nerve.

PMID- 11533537
TI  - Chondrosarcoma of the thoracic spine: total en bloc sagittal resection. A case
      report.
AB  - Chondrosarcomas located in the spine are uncommon tumors and are challenging to
      manage. A case of a 65-year-old man with a T3-T4 spine chondrosarcoma is
      reported. The onset of symptoms consisted in progressive dorsal pain with
      sometimes a girdle-like radiation and, successively, in dysaesthesia and
      paresthesia from the lower limbs to the thoracic region. After preoperative
      oncologic and surgical planning the patient underwent a total en bloc resection
      of the mass. No postoperative adjunctive neurological deficits were recorded. An
      adjuvant radiation therapy with a dose of 5.500 centigrays (cGy) over four weeks
      was performed. At one year follow-up the patient is alive with no signs of
      recurrence on computed tomographic scans and magnetic resonance imaging. We
      discuss this case with particular emphasis on the preoperative planning, the
      surgical procedure and related prognosis.

PMID- 11533538
TI  - Spinal-cord compression due to extradural amyloidosis of the cervico-occipital
      hinge, in a hemodialysed patient. A case report.
AB  - Long-term dialysed patients can develop an arthropathy, called dialysis
      arthropathy, due to the deposition and transformation of the beta2 microglobulin
      into amyloid. The involvement of the spine, called destructive
      spondyloarthropathy (DSA), occurs between 10 and 25 percent; of these patients,
      and sometimes causes neurological damage. The disc space narrowing, vertebral
      body erosion and pseudocystis, in presence of polyarthropathy, chronic renal
      failure, and carpal tunnel syndrome, allows to make a diagnosis of DSA, which is
      proved by histological finding of beta2 microglobulin-amyloid. We report a rare
      case of spinal cord compression due to beta2 microglobulin-amyloid deposit in
      extradural space of cervico-occipital hinge.

PMID- 11533540
TI  - Preoperative cardiac and pulmonary assessment.

PMID- 11533539
TI  - [Bispectral Index: is it really useful for in anesthesia-recovery?].

PMID- 11533541
TI  - Bispectral index monitoring in sevoflurane and remifentanil anesthesia. Analysis
      of drugs management and immediate recovery.
AB  - BACKGROUND: Recent studies have suggested that electroencephalogram bispectral
      index (BIS) monitoring can improve recovery after anaesthesia and save money by
      shortening patients postoperative stay. The aim of the study is to evaluate the
      management of drugs and to measure immediate recovery after anaesthesia with or
      without BIS monitoring. METHODS: We studied 90 patients undergoing abdominal
      surgery randomly allocated to one of two groups of 45 each with or without BIS
      monitoring. Standard monitoring (EKG, arterial oxygen saturation and non-invasive
      blood pressure) was applied. All groups were monitored with BIS, using electrodes
      (Zipprep, Aspect Medical Systems) applied to the forehead. In the group 2 the BIS
      value was blinded to the anaesthesiologist. The BIS value was displayed using
      Spacelabs Medical BIS Ultraview Monitor. After obtaining baseline values for the
      BIS index (group 1) and haemodynamic data (all groups) anaesthesia was induced
      with a bolus dose of remifentanil and TPS, and vecuronium. The anaesthesia was
      maintained with Remifentanil and Sevoflurane. At standard times BIS, haemodynamic
      and respiratory parameters were recorded. Recovery times were measured by a study
      coordinator. Drug consumption was calculated. RESULTS: In group 1 the consumption
      of Sevoflurane decreased by 40 % while the consumption of remifentanil decreased
      by 10 % as compared to group 2. The use of vecuronium did not change in the 2
      groups. In group 1 the time elapsed from cessation of anaesthetics to orientation
      decreased significantly. The difference was 5 min, from 11 to 6 min. CONCLUSIONS:
      BIS monitoring decrease both sevoflurane and remifentanil consumption, when
      compared to anaesthesia without BIS, with an immediate recovery after sevoflurane
      and remifentanil anaesthesia.

PMID- 11533542
TI  - [Fast track in abdominal aortic surgery].
AB  - BACKGROUND: The aim of this work is to evaluate the efficacy of a new
      perioperative approach to improve the outcome and to reduce hospitalisation after
      abdominal aortic surgery. METHODS:  EXPERIMENTAL DESIGN: observational study on
      patients operated from October 1996 to October 1997 (Group 1996), and from
      November 1997 to November 1998 (group 1998). CENTRE: Anaesthesiology Department
      of Regional Hospital. PATIENTS: historical group: 56 patients surgically treated
      with abdominal aortic bypass in 1996. CASE CONTROL GROUP: 58 patients surgically
      treated with abdominal aortic bypass in 1998. INTERVENTION: group 1996:
      maintenance of anaesthesia with forane and fentanyl; postoperative infusion of
      mepivacaine 1% through lumbar epidural catheter. GROUP 1998: preoperative
      anaesthesia through thoracic (T 4) epidural catheter with infusion of bupivacaine
      0.5%; maintenance of anaesthesia with propofol, fentanyl and infusion of
      bupivacaine 0.125%; postoperative infusion of bupivacaine 0.125%, early
      rehabilitation care (early removal of nasogastric tube and urinary catheter,
      early deambulation, feeding and physiotherapy). EVALUATION: analgesia efficacy,
      day of deambulation, day of removal of the urinary catheter and the nasogastric
      tube, day of bowel canalization, day of discharge, major complications. RESULTS:
      In group 1998 analgesia was better. Furthermore a significant improvement
      consisted in the earlier removal of the nasogastric tube and the urinary
      catheter, earlier return of the gastrointestinal function and earlier
      deambulation. The length of stay is significantly reduced. In group 1998 we have
      less complications. CONCLUSIONS: Total intra-venous anaesthesia associated with a
      thoracic epidural anaesthesia, connected with early rehabilitation may improve
      the outcome and reduce the length of stay in patients submitted to abdominal
      aortic surgery.

PMID- 11533543
TI  - [The PiCCO system with brachial-axillary artery access in hemodynamic monitoring
      during surgery of abdominal aortic aneurysm].
AB  - BACKGROUND: The haemodynamic monitor PiCCO System, based on transpulmonary
      arterial thermodilution, has been used with a brachial-axillary access instead of
      the femoral arterial access during abdominal aortic aneurysm surgical repair.
      Accuracy and limitations of pulse contour continuous cardiac output (PCCO) were
      evaluated on the basis of arterial thermodilution cardiac output. The patterns of
      cardiac index, preload, afterload and cardiac function parameters were also
      studied in the different phases of the surgical procedure. METHODS: Twenty
      consecutive patients were studied. Mean differences (bias) between PCCO and
      arterial thermodilution cardiac output were calculated by the Bland-Altman test.
      Analysis of variance with multiple comparison test of haemodynamic variables in
      the different phases were performed. The correlation coefficients between cardiac
      index and the volumetric preload variables were also obtained. RESULTS: Brachial
      artery catheterization was achieved without any major complication. Pulse contour
      continuous cardiac index (CI) and arterial thermodilution CI values showed
      overall mean differences (bias) of -0.04 Lamin-1. m-2 (SD 0.8) but after aortic
      cross-clamping and aortic unclamping they were 0.64 Lamin-1. m-2 (SD 0.57) e 
      0.57 Lamin-1. m-2 (SD 0.85), respectively (p<0.05). CI, global end-diastolic
      volume (GEDV) and intrathoracic blood volume (ITBVI) were significantly lower
      during aortic cross-clamping. CI was not correlated to central venous pressure
      (r=0.18) but instead, to GEDV (r=0.57) and ITBVI (r=0.65). CONCLUSIONS: PiCCO
      System with brachial-axillary arterial access was suitable for haemodynamic
      monitoring of the abdominal aortic aneurysm surgical repair procedures. PCCO must
      be recalibrated with arterial thermodilution after aortic cross-clamping and
      unclamping to avoid an over-estimation and an under-estimation respectively.
      During aortic cross-clamping GEDV and ITBVI indicated a decreased preload. Other
      haemodynamic variables were less valuable but EVLWI showed an interesting steady
      increase during the whole procedure.

PMID- 11533544
TI  - [Plasma substitutes: strategies for use in intensive therapy to maintain a
      correct ratio between therapeutic efficacy and costs].
AB  - BACKGROUND: The coice of one product rather than another in clinical practice is
      based on two main criteria: therapeutic efficacy and the cost of the product in
      question. However, if therapeutic efficacy is equal, the choice of a less
      expensive product is not necessarily the right option. We compared the costs and
      therapeutic efficacy of two products used in plasma replacement therapy in order
      to identify which would be the most advantageous. METHODS: A total of 126
      patients due to undergo major abdominal surgery were recruited and, having been
      duly informed, they were divided into two random groups. One group was treated
      with a solution of hydroxyethylamide 6% with an intermediate molecular weight (MW
      200 kDa SD 0.5), and the other was treated with a solution of modified fluid
      gelatine (MFG) at 4% (MW 30 kDa). The solutions were administered to patients at
      the start of surgery until the morning of the first postoperative day in order to
      maintain mean arterial pressure (MAP) greater than 60 mmHg and central venous
      pressure (CVP) between 10 and 14 mmHg. Moreover, the costs of the two products
      and their additional charges were taken into consideration, taken from the supply
      lists provided by the pharmacy in the hospital where the study was carried out.
      RESULTS: No significant differences were found between the two groups in terms of
      therapeutic efficacy. In economic terms, the cost of the entire infusion
      treatment was comparable between the two groups in spite of the higher cost of
      hydroxyethylamide. CONCLUSIONS: The higher cost of hydroxyethylamide was
      compensated by the fact that a smaller amount of the solution is required to
      obtain the same hemodynamic parameters guaranteed by gelatine. Moreover, no
      adverse reactions were reported in this study to either compound. In the
      international literature, gelatine is associated with adverse reactions in a
      greater number of cases than hydroxyethylamide. This study shows that when
      proposing strategies of use, a simple cost analysis of the products used is not
      sufficient for a correct decision.

PMID- 11533545
TI  - Older adult multiorgan donors and misdiagnosed tumor.
AB  - BACKGROUND: In these last years, the increase in organ donations is mostly due to
      old patients died of primary vascular cerebral diseases. In this kind of patients
      some undiagnosed cancers can be present and can be transmitted to the receiver.
      Aim of this study is to carry out a research in order to identify any undiagnosed
      cancer which can be present during the period of encephalic death. METHODS:
      Perspective study: hospitals type II and type III. Polyvalent intensive care.
      From January 1999 to July 2000 encephalic death has been ascertained in 16
      patients. The research of tumor markers has been carried out on these patients.
      Further diagnostic researches have been carried out on patients who had anomalous
      values. RESULTS: The organ donations have not been made by eight patients: five
      for family refusal, one for medical contraindications, two for the presence of
      undiagnosed tumor (PSA 1100 ng/ml and CEA 129.5 ng/ml) confirmed by prostatic and
      abdominal US imaging. A patient with CA 19-9 89.5 ng/ml has not been examined,
      because of the family refusal to donation. A patient with PSA of 135 ng/ml had a
      negative response from the anal scanner, and so the prosecution of the donation
      has not been interrupted. A blood sample has been taken and a biopsy of the
      prostate has been made to confirm the absence of neoplasm. CONCLUSIONS: It is
      necessary to make a careful examination of the organ donor to check if some
      cancers are present. Tumor markers cannot be used to make a diagnosis of a
      cancer, but they can be used as guide for further researches. In spite of all the
      diagnostic efforts, the objective evaluation of the surgeon is still the most
      important factor like the biopsy of all the suspected lesions during an operation
      and the autopsy.

PMID- 11533546
TI  - [Prevention of mycotic infections in liver transplant recipients: comparison of
      two chemoprophylactic protocols].
AB  - BACKGROUND: The aim of the study was to compare and evaluate the efficacy of two
      chemoprophylactic protocols against mycotic infections in a liver transplant
      recipients population. DESIGN: single-blind, randomized. SETTING: Liver
      transplant Center of a National Health System teaching hospital. METHODS: Eighty
      eight consecutive patients submitted to liver transplantation were enrolled in
      the study. Immediately before surgery they were randomized to receive sequential
      treatment with intravenous liposomal amphotericine B + oral itraconazole or
      intravenous fluconazole + oral itraconazole. Intravenous drugs were administered
      in the first postoperative week, and oral treatments for the following three
      weeks. In addition to analyzing the frequency and incidence of colonization,
      local and disseminated infection of mycotic origin, the causes of death and the
      possible risk factors for mycotic disease have been examined. RESULTS: Eighty
      five patients completed the study. No significative difference was evident in the
      two groups as regards to single organ and systemic fungal infection rate. Two out
      of a total of 5 deaths were related to mycotic disease. Pre-transplant fungal
      colonization, more severe liver disease indicating the transplant procedure and
      the rejection of the graft were all risk factors for the development of mycotic
      infection. CONCLUSIONS: The two protocols used in the study showed and equal
      efficacy in preventing fungal infections in liver transplant recipients.

PMID- 11533547
TI  - Inferior thyroid artery bleeding: a life-threatening complication of non-surgical
      tracheostomy.

PMID- 11533548
TI  - [Circadian variations in the onset of acute myocardial infarction].
AB  - BACKGROUND: Several studies have observed a circadian pattern in the onset of
      acute myocardial infarction (AMI), with a peak incidence in the morning hours. It
      has been suggested that different circadian rhythms may exist in various
      subgroups of patients. METHODS: This study sought to determine whether the
      circadian incidence of AMI varied by sex, age, cardiovascular risk factors,
      previous history of ischemic accidents, the site of AMI, and the short-term
      outcome. These possibilities were examined in a population of 597 consecutive
      patients with AMI, admitted to the coronary care unit. 548 patients have been
      included in the study, 442 men (80.6%) and 106 women (19.4 %); mean age 64.5
      years. RESULTS: A peak incidence of AMI was found between 06.01 a.m. and 12.00
      a.m. (32.4%; p<0.0002). This peak was present in patients 65 years old (33.2%;
      p<0.005), in men (32.5%; p<0.0002) but not in women, in smokers (32.1%; p<0.0005)
      and in those that did not smoke (33.0%; p<0.04), in patients with
      hypercholesterolemia (34.9%; p<0.006 ) and without hypercholesterolemia (31.1%;
      p<0.03). A circadian rhythm was absent in diabetics, hypertensives and in
      patients with a history of previous cardiovascular events. Regarding the site of
      AMI, inferior AMI showed an increased incidence between 06.01 a.m. and 12.00 a.m.
      (36.2%; p<0.002), while the circadian distribution of anterior AMI, as well as
      non-Q wave AMI, did not show this incidence. Finally, higher mortality was
      reported in patients with an AMI onset at night (22.3%). CONCLUSIONS: These
      results give further clues in understanding the external and inner factors acting
      in the morning hours as triggers for AMI.

PMID- 11533549
TI  - [Myocarcial revascularisation without extracorporeal circulation: current
      indications, surgical technique and results].
AB  - BACKGROUND: This study was undertaken to assess our experience of the evolution,
      over time, of beating heart surgery in the Cardiologic Center Foundation Monzino.
      METHODS: From March 1995 to June 2000, 506 patients underwent myocardial
      revascularization on beating heart: 313 until May 1999, and 193 between June 1999
      and June 2000, after the advent of coronary artery stabilizers and shunts, to
      keep the surgical field bloodless, with minimal motion and continuous myocardial
      perfusion. Surgical accesss was via a median sternotomy for 408 cases and via a
      left anterior thoracotomy for 98 cases. RESULTS: The indications by choice
      increased, from I to II period, from 61% to 83% with special situations in which
      patients had three-vessel coronary artery disease raised from 33% to 50%,
      concerning also bypass grafts performed on circumflex artery and right coronary
      increased. Postoperative mortality in hospital decreased from 1.3% to 0.5% and
      perioperative IMA (acute myocardial infarction) from 3.8% to 0.5% in patients
      undertaken to median thoracotomy. Hospital stay decreased from 8 to 7 days about
      [no significant differences with patients who underwent CPB (cardiopulmonary
      bypass)]; in patients who underwent to MTS (left anterior minithoracotomy) there
      was no deaths, IMA decreased from 3.9% to 0% and hospital stay from 6 to 5 days.
      Grafts patency increased from 92.3% to 100%. CONCLUSIONS: To perform completed
      revascularisations is possible now even on the beating heart, and also to make
      precise anastomosis as on pump CABG, in a reproducible and easy way. The beating
      heart procedure, that is also more economical, might be expanded to all patients,
      not only high risk patients.

PMID- 11533550
TI  - What drug must be used to avoid the most common hypertensive complications?
AB  - After recalling that cardiovascular complications represent the most frequent
      cause of mortality and morbidity in hypertensive patients, the author describes
      the main mechanism responsible for increased plasma level concentrations of
      Angiotensin in this syndrome. He subsequently illustrates the effects of ACE
      inhibitors, differentiating them from AT1-receptors. The anti-hypertensive
      actions of new b-blockers, like Carvedilol and Nebivolol are also explained. In
      addition, the anti brain hemorrhage and heart-failure effects of diuretics in
      hypertensive patients are briefly summarised. Finally, the anti-calcinotic effect
      and anti-embolic action of calcium-antagonist drugs are also underlined.

PMID- 11533551
TI  - Atrial natriuretic factor and mitral valve prolapse syndrome.
AB  - Mitral valve prolapse (MVP), is the most frequent valvulopathy, although it is
      difficult to evaluate its incidence since this pathology is often asymptomatic.
      However, in some patients a rich variety of symptoms such as chest pain, dyspnea,
      palpitations, syncope, dizziness, panic attacks and autonomic dysfunctions have
      been found. The pathogenesis of these symptoms, incompletely understood, appears
      to be multifactorial, related to altered autonomic function, adrenergic
      responsiveness and to combinations of these factors. In patients with MVP a
      variety of neuroendocrine anomalies has been found: high epinephrine and
      norepinephrine plasma levels, altered rennin-angiotensin-aldosteron (RAA)
      response to volume depletion and orthostatic stimulation, and high plasma levels
      of atrial natriuretic factor (ANF) especially in hypovolaemic individuals. The
      role of ANF could be important in the genesis of MVP syndrome, it could
      contribute to determine: the imbalance between the sympathetic and
      parasympathetic system, the altered RAA response to orthostatic stimulus, the
      volemic and venous flow reductions (with a direct action, other than diuretic and
      natriuretic action). Factors that can determine ANF secretion abnormality in MVP
      could be: 1) Mitral regurgitation; 2) increased heart rate and the high
      incidence, in MVP syndrome, of arrhythmias; 3) central nervous system
      neuroendocrine imbalance; 4) increased catecholamines secretion.

PMID- 11533552
TI  - Venous thromboembolism and melanoma.
AB  - The association between venous thromboembolism and cancer has been known for many
      years. The clotting system may be activated because of enhanced platelet
      aggregation and adhesion or by stimulation from the endothelial cells or the
      tumour cells themselves. Furthermore, thrombosis may develop as a result of
      prolonged immobilization, surgery, chemotherapy or hormone therapy. We present a
      case of a patient who underwent surgery for excision of a Clark level II melanoma
      on the back who developed pulmonary metastasis four years after the operation.
      The metastasis manifested with very severe venous thromboembolism which, despite
      anticoagulant therapy and the placement of a vena caval filter, led to the
      patient's death from pulmonary embolism. The case is uncommon, in terms of both
      the rarity with which venous thromboembolism is associated to melanoma, and the
      severity with which it manifested.

PMID- 11533553
TI  - [Right ventricular heart failure in hyperthyroidism].
AB  - Cardiovascular disorders in patients affected with hyperthyroidism are very
      common; the increase in the heart rate and in inotropism combines with a rise in
      the cardiac index towards which the reduction in peripheral resistances and an
      increase in the venous return to the heart contribute. The increase in myocardial
      excitabi1ity, caused above all by triiodothyronine, may be attended with atrial
      extrasystoles or even with atrial fibrillation. Congestive heart failure during
      hyperthyroidism, even if rare, may either reveal itself in association with pre
      existent cardiopathy or to be precipitated by tachyar-rhythrmia, particu1arly, by
      paroxysmal atrial fibrillation. The case is described of a young woman affected
      with Graves' disease, presenting an ingravescent dyspnoea, in which sinusal
      tachycardia, the S1Q3 electrocardiographic figure and the echocardiographic
      reports of a right ventricu1ar overload with pulmonary hypertension and systemic
      venous congestion, suggest picture of acute pulmonary embolism. The isolated
      dysfunction of the right ventricle resolved quickly after an adequate antithyroid
      therapy. The oddness of presentation of Graves' disease in this case would
      suggest the execution of the thyroid profile for all patients with a primary
      diagnosis of heart failure, in order to single out hyperthyroid subjects with
      reversible myocardial dysfunction.

PMID- 11533554
TI  - Atherosclerotic aneurysm of the left main coronary artery. Case report and review
      of the literature.
AB  - Coronary artery aneurysms involve the right coronary artery, the left anterior
      descending and the left circumflex coronary arteries in descending order of
      frequency; aneurysms involving the main left coronary artery are extremely rare.
      Atherosclerosis is the most common cause. Only eleven patients surgically treated
      with atherosclerotic left main coronary artery aneurysms are reported. We
      observed the twelfth case of atherosclerotic aneurysm of the left main coronary
      artery, successfully treated. In a 65-year-old man we found a large aneurysm
      originating at the distal segment of the left main coronary artery. A
      thromboendarterectomy was per-formed and was extended back into the left main and
      down the left anterior descending artery. An aneurysmorrhaphy and a three-vessel
      coronary artery bypass grafting were also performed. Three years later the
      patient was asymptomatic. Management of these cases is still controversial and
      based on anedoctal experience rather than controlled trials. Although surgery has
      been recommended to prevent complications, there are no available data comparing
      medical and surgical management. We feel that coronary bypasses should be
      performed in coronary artery aneurysm patients only when indicated by the
      severity of stenosis or progressive angina despite medical therapy. It is our
      opinion that anurysmorraphy should preserve native flow as much as possible.

PMID- 11533555
TI  - Ultrasound duplex as a sole exam for surgical purposes in lower limb arterial
      obstructive disease.
AB  - BACKGROUND: The aim of the research is to value the efficacy of ultrasound duplex
      as a sole preoperative exam in peripheral Arterial Obstructive Disease (PAOD).
      Angiography is undoubtedly known as the gold standard, though its risks and
      complications. In the last decades duplex scanning and its variant, has proven to
      be an irreplaceable tool in the diagnosis of these disease. METHODS: We evaluated
      five previous studies that compare angiography to duplex scanning. RESULTS: Out
      of 273 cases, 207 (73.8%) had a good correspondence between the two methods;
      besides if we consider each arterial tract duplex reliability is better in distal
      diseases (159 cases out of 200, 79.5%) than in proximal (48 out of 73.65%)
      contrasting with an other meta-analytic evaluation made by Koelemay et al.
      Moreover we wanted to verify our personal experience, by the intention to treat
      method, if the surgical operation selected for our patients would have been the
      same based only on pre-operative echo-duplex scanning. After the analysis of
      about 20 files the research was interrupted because there was a perfect
      correspondence between the two exam only in three cases, all of them re-operation
      for graft branches obstruction. The lacks of duplex has been: 1) non
      identification of important lesions on the aorto-iliac tract; 2) insufficient
      location of distal disease. CONCLUSIONS: The angiography results the fundamental
      choice in the treatment of PAOD particularly in the distal tracts. Debatable is
      the role of echography in aorto-iliac portion, where a number of lesions may be
      effectively treated by endovascular procedures.

PMID- 11533556
TI  - Effect of training on accumulated oxygen deficit and shuttle run performance.
AB  - BACKGROUND: The purpose of the present study was to investigate changes in
      physiological, metabolic and performance parameters resulting from an intense 6
      week training programme. METHODS: Sixteen volunteers were divided into a control
      (CN; 4 men and 2 women) and training group (TR; 6 men and 4 women). Laboratory
      measures included maximal aerobic power (VO2max), submaximal oxygen uptake (10.5
      percent or 6 degrees treadmill inclination) and accumulated oxygen deficit (AOD).
      Performance was assessed during 20 metre shuttle run tests (PST, progressive
      shuttle run test; HIST, high intensity shuttle run test). RESULTS: TR improved
      their HIST performance (m) significantly compared with CN, identified by a
      significant "group-by-training" interaction (p<0.01). Similarly, AOD values
      improved more in TR compared with CN (p<0.01). There was a trend for TR to
      further reduce blood pH values after training compared with CN, although this
      decrease (approximately 0.05 units) did not attain statistical significance. The
      change in AOD was strongly correlated with the change in run time to exhaustion
      (r=0.76, p<0.01) and the change in estimated total work output (r=0.69, p<0.01)
      during 10.5 percent gradient running and modestly correlated with the change in
      HIST performance (r=0.49, p<0.05, assuming a directional test). CONCLUSIONS: The
      results of the present study suggest changes in the anaerobic capacity,
      determined as AOD, due to training may be reflected in corresponding changes in
      laboratory and field performance.

PMID- 11533557
TI  - Age related neural adaptation following short term resistance training in women.
AB  - BACKGROUND: This study examined the influence of age on neural facilitation and
      neural cross-education following short term unilateral dynamic resistance
      training with the hypothesis that older women may have a diminished ability for
      adaptation. METHODS:  EXPERIMENTAL DESIGN: This was a prospective, repeated
      measures design. The non-dominant left arm served as a control limb and follow-up
      testing was performed two weeks after pretesting. SETTING: Testing was conducted
      in the Neuromuscular Research Laboratory at the University of Oklahoma. PATIENTS:
      20 females (n=10, young (YF) 20.8+/-0.1 yrs; n=10, older (OF) 58.1+/-0.14) were
      assessed. INTERVENTIONS: 14 days of training of the right elbow flexors only. On
      each day, subjects performed four sets of ten repetitions using 70 percent of
      maximal strength of the biceps brachii. MEASURES: The following variables in both
      right and left elbow flexor muscle groups were evaluated; isometric strength
      (IMS), efficiency of electrical activity (EEA) and estimated upper arm cross
      sectional area (CSA). RESULTS: There were significant increases (p<or=0.01) in
      IMS of both the right (28 percent) and left (12-15 percent) muscle groups for
      both age groups. Strength improvements were explained by neural adaptation since
      there were no changes in upper arm CSA but consistent decreases in EEA (12-16
      percent). While OF had consistently lower values for all variables, there were no
      significant age effects. CONCLUSIONS: Short term unilateral dynamic resistance
      training is a sufficient stimulus to induce significant strength increases in
      both trained and untrained contralateral limbs and that a neural mechanism is
      responsible for the muscular adaptation in both young and older women.
      Implication exists for unilateral stroke victims, individuals with single hip or
      knee replacements, or single limb casts.

PMID- 11533558
TI  - The effect of multi-cycle-run blocks on pulmonary function in triathletes.
AB  - BACKGROUND: This study was designed to determined the pulmonary responses
      elicited by multi-cycle-run exercise in triathletes and to compare them to those
      elicited during a simple cycle-run succession. METHODS: Twelve male triathletes
      underwent three successive laboratory trials: 1) an incremental cycle test, 2) 30
      min of cycling followed by 20 min of running (C-R), and 3) five repeated bouts of
      6 min of cycling and 4 min of running (X-CR). Before and 10 minutes after the
      third and fourth trials, the triathletes underwent lung function testing,
      especially spirometry and diffusing capacity testing for carbon monoxide
      (DL(CO)). During all trials, ventilatory data were collected every minute using
      an automated breath-by-breath system. RESULTS: The results showed that: 1) the
      cardiorespiratory responses observed during running were greater in the X-CR
      trial for VE/VCO2 and HR, 2) DL(CO) and DL(CO)/VA were significantly reduced
      after both trials, and 3) there were no significant changes in pulmonary volumes.
      CONCLUSIONS: We concluded that 1) the multi-block trial elicited greater
      cardioventilatory responses than simple the cycle-run succession and 2) multi
      block seems a good method to stimulate the specific adaptations required for the
      cycle-run succession, and particularly for the cycle-run transition. In any case,
      the efficacy of the multi-block model needs to be more thoroughly evaluated over
      the course of a longer-term training programme.

PMID- 11533559
TI  - The effects of sprint (300 m) running on plasma lactate, uric acid, creatine
      kinase and lactate dehydrogenase in competitive hurdlers and untrained men.
AB  - BACKGROUND: High intensity exercise may induce muscle damage especially in
      individuals unaccustomed to regular physical efforts. Our aim was to compare the
      impact of 300 m sprint running on muscle enzymes release into blood in
      competitive hurdlers and untrained but physically fit adults. METHODS: 
      EXPERIMENTAL DESIGN: Comparative study. SETTING: General community. PARTICIPANTS:
      Nine competitive hurdlers (CH; 21.3 yrs+/-3.1) and six matched moderately active
      untrained men (UT). INTERVENTIONS: Subjects performed a single 300 m sprint
      running test. MEASURES: Plasma creatine kinase (CK) and lactate dehydrogenase
      (LD) activities, and concentrations of lactate (LA) and uric acid (UA) measured
      before the warm-up and 5 min, 2 and 20 hrs postrun. RESULTS: Mean runner
      performance achieved by CH was significantly better (35.53-s+/-0.64) and LA
      concentrations significantly higher (14.95 mM+/-0.59) than those recorded in UT
      (41.52-s+/-2.22; 10.13 mM+/-0.59). Pre- and postrun CK activities until the 2nd
      hour of recovery were found to be significantly higher (p<0.05) in CH than in UT,
      whereas LD activities were similar in both groups pretest, but significantly
      higher in UT immediately postrun. In CH, the highest CK activity (32 percent
      increase) was recorded immediately post-test, whereas in UT the peak CK (135
      percent increase) was attained in the 20th hour of recovery. In both groups UA
      reached the peak level in the 2nd hour of recovery. CONCLUSIONS: More pronounced
      and delayed postrun increase in CK, as recorded in UT, may provide evidence of a
      larger exercise-induced muscle injury in the untrained adults. Higher
      postexercise UA levels as recorded in CH might account for a more marked
      involvement of adenylate kinase reaction in ATP resynthesis.

PMID- 11533560
TI  - The reliability and validity of the Astrand nomogram and linear extrapolation for
      deriving VO2max from submaximal exercise data.
AB  - BACKGROUND: While the accepted measure of aerobic power remains the VO2max this
      test is extremely demanding even for athletes. There are serious practical and
      ethical concerns in attempting such testing in non-athletic or patient
      populations. An alternative method of measuring aerobic power in such populations
      is required. A limited body of work exists evaluating the accuracy of the Astrand
      Ryhming nomogram and linear extrapolation of the heart rate/oxygen uptake plot.
      Issues exist in terms of both equipment employed and sample numbers. METHODS:
      Twenty-five normal subjects (mean age 28.6, range 22-50) completed 52 trials
      (Bruce treadmill protocol) meeting stringent criteria for VO2max performance.
      Respiratory gases were measured with a portable gas analyser on a five-sec sample
      period. The data was analysed to allow comparison of the reliability and validity
      of linear extrapolations to three estimates of heart rate maximum with the
      Astrand nomogram prediction. RESULTS: Extrapolation was preferable yielding
      intraclass correlation co-efficients (ICC) of 0.9433 comparable to that of the
      observed VO2max at 0.9443 and a bias of -1.1 ml x min(-1) x kg(-1) representing a
      2.19 percent underestimate. CONCLUSIONS: This study provides empirical evidence
      that extrapolation of submaximal data can be employed with confidence for both
      clinical monitoring and research purposes. With the use of portable equipment and
      submaximal testing the scope for future research in numerous populations and non
      laboratory environments is considerably increased.

PMID- 11533561
TI  - Reliability of a 5-min running field test and its accuracy in VO2max evaluation.
AB  - BACKGROUND: Five-min running field test (5_RFT) was established for determining
      individuals' maximal aerobic velocity (V(amax)) and functional aerobic capacity
      (VO2peak) during horizontal run. We determined the number of trials required for
      establishing high reliability of the 5_RFT and examined its accuracy in
      evaluating individuals' maximal aerobic capacity (VO2max). METHODS: The
      V(amax)(5) recorded during the 5_RFT on four separate days was compared in 45
      subjects (14 male, 31 female, 17.0+/-0.2 yrs) of various levels of physical
      fitness. The accuracy of VO2max evaluation using V(amax)(5) was examined via
      regression analysis in additional 23 male subjects (20.7+/-0.3 yrs). RESULTS: The
      mean correlation coefficient of V(amax)(5) among four trials was 0.94. Intraclass
      reliability coefficient across all trials was 0.98. For trial 3 and 4, the mean
      value of subjects' V(amax)(5) was higher than that of trial 1 and 2. V(amax)(5)
      of trial 2 was also higher than that of trial 1 while no difference was found
      between trial 3 and 4. F-test of equality of variances demonstrated similar
      sample variance of V(amax)(5) in all trials. Within-subject coefficient of
      variation in V(amax)(5) was 3.7 percent for all trials was reduced to 2.4 percent
      for trial 3 vs 4. For examining the accuracy in VO2max evaluation, regression
      analysis revealed that the V(amax)(5) explained 35.0 percent of the variance of
      measured VO2max (SEE = 5.64 ml x kg(-1) x min(-1)). CONCLUSIONS: The 5_RFT is
      reliable in determining V(amax)(5). Nevertheless, two familiarization sessions
      are recommended for achieving the best performance in the test. The 5_RFT cannot
      evaluate VO2max with reasonable accuracy in young males.

PMID- 11533562
TI  - Effect of sustained adrenergic receptors stimulation and blockade on lactate
      threshold in rats.
AB  - BACKGROUND: This study examined the hypothesis that prolonged (12 hrs)
      stimulation of adrenergic receptors by adrenaline and their blockade by regitine
      (alpha-blockade) or propranolol (beta-blockade) affect lactate thresh-old (T(LA))
      and exercise tolerance in rats. METHODS: Twenty-four untrained male Wistar rats
      performed a multistage running test on a treadmill with an intensity increased
      from 13 m/min to the maximum speed. After a control exercise test the animals
      were devided into three groups implanted s.c. with: 1) adrenaline; 2) propranolol
      and 3) regitine tablets. Twelve hours after the tablet implantation the exercise
      was repeated. Both before the exercise test and at the end of each 2-min loads
      blood lactate [LA] was measured to evaluate T(LA). RESULTS: Prolonged adrenaline
      excess resulted in reduced maximal running speed and shifted T(LA) towards lower
      exercise intensities than in the control test. Both alpha- and beta-adrenergic
      blockade reduced the work load at which T(LA) occurred, without changing the
      maximum running speed and maximal blood LA concentration. Blood [LA] at the
      lactate threshold ([LA] at T(LA)) was significantly higher in hyperadrenalinemic
      than in control rats, whilst under beta-blockade it was lowered in comparison
      with control values. Alpha-adrenergic blockade had no effect on [LA] at T(LA),
      but at the higher exercise intensities blood [LA] exceeded the respective control
      values. CONCLUSIONS: The present study demonstrated that prolonged excess of
      adrenaline reduces the maximum power output and T(LA). The former effect seems to
      be a result of simultaneous stimulation of both types of adrenergic receptors.

PMID- 11533563
TI  - Effect of training status on the sympathoadrenal activity during a supramaximal
      exercise in human.
AB  - BACKGROUND: The study investigated the concentrations of plasma catecholamine,
      adrenaline (A) and noradrenaline (NA), and the adrenal medulla responsiveness to
      the sympathetic nervous activity in sprinters (S), endurance runners (E) and
      untrained subjects (U) during a supramaximal exercise (the Wingate-test).
      METHODS: A group of 19 men took part in the tests: 6 S (20.5+/-0.7 years), 6 E
      (21.0+/-1.0 years) and 7 U (20.9+/-0.4 years). The maximal power (Wmax) and the
      mean power (W) were determined from the Wingate-test on a cycle ergometer. The
      plasma lactate, A and NA were analysed at rest (La0, A0 and NA0), immediately at
      the end of the exercise (Amax and NA(max)) and after 5 min recovery (La(max), A5
      and NA5). The disappearance of A and NA was judged by the difference between the
      maximal values and those determined after 5 min recovery (Amax-A5 and NA(max)
      NA5) and the ratio A/NA was considered as an index of the adrenal medulla
      responsiveness to the sympathetic nervous activity. RESULTS: During the Wingate
      test S exhibited higher performances and higher La(max) than the two other
      groups. At the end of the Wingate-test the NA(max) values were similar in the
      three groups whereas the Amax values were significantly higher in S than in E and
      U (8.00+/-0.5 nmol x l(-1) in S vs 3.47+/-0.30 nmol x l(-1) and 3.29+/-1.14 nmol
      x l(-1) respectively in E and U). This leads to a higher Amax/NA(max) ratio for S
      compared to the other two groups (0.77+/-0.10 in S vs 0.23+/-0.03 and 0.28+/
      0.05, respectively in E and U). As the disappearance of A (Amax-A5) was
      significantly higher in S (6.80+/-0.47 nmol x l(-1) in S vs 2.64+/-0.19 nmol x l(
      1) and 1.64+/-1.37 nmol x l(-1), respectively in E and U), the higher values of
      Amax in S could be explained by an increase of the adrenal medullary secretory
      capacity in this group. CONCLUSIONS: It was concluded that essentially short term
      and intense exercises as sprint ones or interval-training may alter the adrenal
      medulla responsiveness to supramaximal exercise but not long duration exercises.

PMID- 11533564
TI  - Physiological profile of very young soccer players.
AB  - BACKGROUND: There is still much uncertainty and debate surrounding the
      physiological requirements of competitive soccer. The coaching emphasis on skill
      development, deficiencies in fitness training, conservative training methods lead
      to difficulty in the scientific study of soccer. METHODS: The physiological
      profiles of 22 young soccer players (mean age = 8.0+/-0.3 years, body mass =
      28.2+/-3.2 kg, body height = 132.4+/-4.3 cm and body fat = 19.4+/-1.6 percent)
      were measured by the incremental exercise protocol on the treadmill with 5
      percent inclination. All boys systematically trained at least 2 years with a
      minimum of two training units per week. During preseason, they trained two times
      per week, and during the competitive season they trained at least three times and
      competed in one or two games per week. RESULTS: Mean VO2max x kg(-1) was 56.7+/
      4.9 ml x kg(-1) x min(-1). Mean value of maximal running speed on a treadmill
      with 5 percent of inclination was 12.0+/-0.9 km x h(-1). Mean values of Rmax =
      1.11+/-0.07. The selected functional variables at the ventilatory threshold (VT)
      level corresponded to VO2 x kg(-1) = 42.9+/-5.0 ml x kg(-1) x min(-1), mean
      values of percent VO2max x kg(-1) at VT level were 76.5+/-1.3 percent, mean speed
      of running was 10.5+/-1.2 km x h(-1), mean values of percent Vmax at VT level
      were 87.5+/-1.9 percent. The mean of energy cost of running was 4.28+/-0.19 J x
      kg(-1) x m(-1). According to our results, we can conclude that the physiological
      characteristics of young soccer players about 8 years old should be as follows:
      VO2max x kg(-1) higher than 55 ml x kg(-1) x min(-1) in defenders, and higher
      than 60 ml x kg(-1) x min(-1), in midfielders and forwards. Maximal speed of
      running on the treadmill with 5 percent of inclination should be higher than 12
      km x h(-1) in all players, the running speed at anaerobic threshold (5 percent)
      higher than 10.5 km x h(-1), percent VO2max at anaerobic threshold level higher
      than 77.0 percent, and the energy cost of running lower than 4.20 J x kg(-1) x m(
      1). CONCLUSIONS: As in other sports where skills play a decisive role, the
      physiological data cannot be the sole predictor of competitive success. On the
      other hand, we must note that these physiological norms and standards are
      necessary conditions for success in high levels of soccer competition. The norms
      play decisive role in talent selection.

PMID- 11533565
TI  - Effects of plyometric training followed by a reduced training programme on
      physical performance in prepubescent soccer players.
AB  - BACKGROUND: In adult population, stretch-shortening cycle exercise (plyometric
      exercise) is often used to improve leg muscle power and vertical jump
      performance. In children, limited information regarding this type of exercise is
      available. The purpose of this study was to examine the effectiveness of
      plyometric training and maintenance training on physical performances in
      prepubescent soccer players. METHODS: Twenty boys aged 12-13 years was divided in
      two groups (10 in each): jump group (JG) and control group (CG). JG trained 3
      days/week during 10 weeks, and performed various plyometric exercises including
      jumping, hurdling and skipping. The subsequent reduced training period lasted 8
      weeks. However, all subjects continued their soccer training. Maximal cycling
      power (Pmax) was calculated using a force-velocity cycling test. Jumping power
      was assessed by using the following tests: countermovement jump (CMJ), squat jump
      (SJ), drop jump (DJ), multiple 5 bounds (MB5) and repeated rebound jump for 15
      seconds (RRJ15). Running velocities included: 20, 30 and 40 m (V20, V30, V40 m).
      Body fat percentage (BF percent) and lean leg volume were estimated by
      anthropometry. RESULTS: Before training, except for BF percent, all baseline
      anthropometric characteristics were similar between JG and CG. After the training
      programme, Pmax (p<0.01), CMJ (p<0.01), SJ (p<0.05), MB5 (p<0.01), RRJ15 (p<0.01)
      and V20 m (p<0.05), performances increased in the JG. During this period no
      significant performance increase was obtained in the CG. After the 8-week of
      reduced training, except Pmax (p<0.05) for CG, any increase was observed in both
      groups. CONCLUSIONS: These results demonstrate that short-term plyometric
      training programmes increase athletic performances in prepubescent boys. These
      improvements were maintained after a period of reduced training.

PMID- 11533566
TI  - Physiological profile of handball players.
AB  - BACKGROUND: The purpose of this study was to determine the physiological profile
      of handball players compared to sprinters, endurance trained and untrained
      subjects. METHODS: Forty-six subjects aged between 19 and 28 years took part in
      this study: 10 were national handball players (NHB); 7 were international
      handball players (IHB), 11 were sprint trained subjects (ST); 8 were endurance
      trained subjects (ET); and 10 were untrained subjects (UT). They performed an
      incremental treadmill test to determine the maximal oxygen uptake (VO2max), and a
      Wingate anaerobic test (WanT) to determine maximal power (Wmax). Plasma lactate
      (La) concentration was measured 5 minutes after the end of the Wingate-test.
      RESULTS: The VO2max of NHB was similar to that of the IHB and ST athletes but
      higher than that of the untrained and lower than the endurance trained athletes.
      Values for Wmax were similar in the IHB and NHB groups and very close to the
      sprinters. When normalized for body mass or to lean body mass, Wmax was greater
      in handball players when compared to untrained or endurance trained subjects.
      Lactate values were in the same range in the NHB, IHB and ST groups and were
      statistically higher in the NHB and IHB groups than in the UT or ET groups.
      CONCLUSIONS: The results suggest that the anaerobic metabolism seems to be
      important for the handball players similarly to sprinters. Since handball is
      known as a sport with typically short exercise periods of high intensity
      alternating with rests, anaerobic metabolism appears then to be higbly relevant
      to performance.

PMID- 11533567
TI  - Knee extension strength and vertical jumping performance in nordic combined
      athletes.
AB  - BACKGROUND: The purpose of this study was to measure knee extension strength and
      vertical jumping performance characteristics in nordic combined athletes.
      METHODS: Unilateral knee extension isometric maximal force (MF) and rate of force
      development (RFD) were measured by a special dynamometer, and unilateral
      isokinetic peak torque (PT) at angular velocities of 60 and 180 deg/sec by a
      Cybex II dynamometer. Maximal squat (SJ) and counter-movement jumps (CMJ) were
      performed on force platform. Nine nordic combined athletes as the experimental
      group and 12 untrained male university students as the control group
      participated. RESULTS: Nordic combined athletes had a greater (p<0.05) absolute
      and relative (body mass-related) values of knee extension isometric MF and
      isokinetic PT, isometric RFD as well as jumping height in SJ and CMJ, than
      controls. The jumping height in CMJ was greater (p<0.05) compared with SJ only in
      nordic combined athletes. Jumping height in SJ and CMJ correlated significantly
      (p<0.05) with knee extension isometric RFD (r=0.62-0.83) and isokinetic PT at
      angular velocity of 60 deg/sec (r=0.70-0.82) in nordic combined athletes and
      untrained men. No significant correlation was obtained between unilateral knee
      extension isometric MF and isokinetic PT or vertical jumping height. CONCLUSIONS:
      The present study demonstrated a markedly higher voluntary maximal and explosive
      force-generating capacity of the extensor muscles of lower extremities in nordic
      combined athletes compared with untrained men, which indicates the adaptation to
      specific explosive type of strength training.

PMID- 11533568
TI  - Reproducibility and reliability of measurements using a linear isokinetic
      dynamometer, Aristokin.
AB  - BACKGROUND: This study was performed to investigate the intra-observer
      reproducibility and reliability of measurements using a linear isokinetic
      dynamometer (Aristokin). METHODS: Sixteen female volunteers (age 18 to 23 years)
      participated in 4 test sessions, each consisting of 6 warming-up movements
      followed by 6 repetitions of 4 different movements. During each session, the
      subjects consecutively performed lifting movements by flexing elbows and
      shoulders (at 65 cm per sec), total lifting movements with arms and legs (at 65
      cm per sec), and extension movements of the legs in sitting position (at 40 and
      60 cm per sec). The first 3 test sessions were performed at a weekly interval,
      the 4th was executed 4 weeks after the 3rd session. Force, power and explosivity
      (force developed per sec) were recorded. RESULTS: The intra-observer
      reproducibility was investigated of the 6 repetitions of the movements during
      each test session. The highest reproducibility for mean peak power and force was
      found in the combination of the 3rd, 4th, 5th and 6th measurement (intraclass
      correlation coefficient 0.85 to 0.99). Using this combination, the intra-observer
      reliability was investigated, defined as the consistency of results obtained
      during the 4 test sessions, performed at a weekly or longer interval. Comparison
      between these sessions showed that the results for mean force in the arm movement
      differed significantly (p=0.01) although a high between sessions correlation was
      found (0.96). Results for mean force and power for the 3 other movements were
      reliable, and no significant learning effect was observed. Lower reliability and
      reproducibility were observed for other parameters including explosivity and
      power and force at the first 0.25 sec of the test movement. CONCLUSIONS: Even
      after standard warming-up movements, the first 2 out of 6 measurement repetitions
      during a test session are not reproducible and should not be used in calculations
      of the results. For the combination of the 3rd to 6th repetitions, a high
      reliability was found for the measurement of mean force and power of the total
      lifting movement and of the sitting leg extension movements repeated in 4
      sessions over a period of 6 weeks.

PMID- 11533569
TI  - The stretch-shortening cycle of the internal rotators muscle group measured by
      isokinetic dynamometry.
AB  - BACKGROUND: The ability to measure the stretch-shortening cycle of isolated
      muscle groups has been limited. The purpose of this study was to measure the
      stretch-shortening cycle of the internal rotator muscle group. METHODS: Sixty
      eight volunteer subjects, 35 men and 33 women, participated in one test session;
      eight men and eight women also participated in a retest session; to examine the
      reliability of the test. A concentric contraction of the dominant internal
      rotator was measured for peak torque, standardized peak torque, power,
      standardized power and acceleration time on a Cybex Norm isokinetic dynamometer
      under three conditions: 1) concentric contraction only, 2) isometric preload
      before a concentric contraction, and 3) eccentric preload before a concentric
      contraction. RESULTS: Condition 3 showed a significant increase in peak torque
      production compared to condition 1 (p=0.001). Conditions 2 and 3 showed a
      significant increase in power production compared to condition 1 (p=0.0001,
      p=0.003). A significant difference was found in all three conditions between the
      men and women, with the men producing greatest peak torques and powers.
      CONCLUSIONS: The testing protocol was found to have high reliability. This
      testing protocol could be used to further study the stretch-shortening cycle in
      the internal rotator muscle group.

PMID- 11533570
TI  - Effects of step aerobics and aerobic dancing on serum lipids and lipoproteins.
AB  - BACKGROUND: To examine the effect of 8 weeks of step aerobics and aerobic dancing
      on blood lipids and lipoproteins. METHODS:  EXPERIMENTAL DESIGN: Comparative
      training. SETTING: Two months of physical fitness program. PARTICIPANTS: Forty
      five sedentary female college student volunteers randomly assigned to one of the
      three groups as step aerobics (n=15), aerobic dancing (n=15) and the control
      group (n=15). The step aerobics and aerobic dancing groups participated in
      sessions of 45 min per day, 3 days per week for 8 weeks with 60-70 percent of
      their heart rate reserve. MEASURES: Total cholesterol (TC), triglyceride (TG),
      low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol
      levels (HDL-C), the ratio of total cholesterol to high-density lipoprotein
      cholesterol (TC:HDL-C). RESULTS: At the end of the 8 week period, a significant
      difference has been found between the step aerobics group and the control group
      and between the aerobic dancing group and the control group in TC levels
      (F[2,44]=8.38; p<0.01). A significant difference in HDL-C levels (F[2,44]=3.65;
      p<0.05) and TC:HDL-C ratio (F[2,44]=11.56; p<0.01) has been found only between
      the step aerobics group and the control group. CONCLUSIONS: These results
      indicate that step aerobics training is an effective training mode for modifying
      lipid and lipoprotein profiles of female college-aged students.

PMID- 11533571
TI  - Acute exercise: response of HDL-C, LDL-C lipoproteins and HDL-C subfractions
      levels in selected sport disciplines.
AB  - BACKGROUND: High HDL levels has been shown to be associated with high endurance
      capacity. The acute effects of maximal endurance exercise (of short duration) (15
      min) on low density lipoproteins-cholesterol (LDL-C), high density lipoproteins -
      cholesterol (HDL-C) and HDL subfractions HDL2 and HDL3 were examined, in order to
      determine whether the magnitude of response can be affected by maximal intensity
      of exercise (incremental stress test). METHODS: Male athletes (n=78) of national
      level, from four sport disciplines, volunteered to participate in this cross
      sectional study; basketball (n=10), swimming (n=9), long distance (LD) running
      (n=23) and wrestling (n=35); also a group of non athletes as controls (n=19).
      Participants trained at least 2 hrs/day for more than 3 years; they were healthy,
      non-smokers and fasted 12 hrs before blood sampling. The ergometric test was a
      test for the estimation of maximal oxygen uptake on a treadmill ergometer based
      on a stepwise stress protocol. RESULTS: Immediately after a maximal effort all
      groups (controls included) showed significant HDL-C increases (p<0.001) from rest
      values, while LD running showed the highest values. HDL2 levels increased in LD
      running (p<0.001), basketball and wrestling, while HDL3 ones in all groups and
      controls (p<0.001). The HDL2 of all athletes showed the highest correlation
      (R=0.37**, p<0.01) with VO2max, even higher than HDL itself. CONCLUSIONS: Acute
      maximal endurance exercise (100 percent VO2max) may induce acute modifications
      and intermolecular redistribution of HDL-C and subfractions. It is possible that
      the increased flux of lipids to HDL-C molecule may result from the regulatory
      action of lipoprotein lipase (LPL).

PMID- 11533572
TI  - Croatian rugby project. Part II: injuries.
AB  - BACKGROUND: Studies of rugby injuries in countries where rugby is not popular are
      rare. The aim of the study was to analyze the epidemiology and other
      characteristics of injuries in the first Croatian-Slovenian rugby league (CSRL)
      and the influence of anthropometric characteristics, body composition and
      constitution on the epidemiology of injuries. METHODS: Eleven anthropometric
      measures for the assessment of anthropometric characteristics, body composition
      and constitution were obtained in a sample of 111 voluntarily participating rugby
      players from the CSRL in the middle of the season 1996/97. After the season a
      questionnaire about injuries sustained in the past season was retrospectively
      filled up by 106 players who finished the first part of the study. Injuries were
      classified according to Garraway and Macleod and the 9th revision of the
      International Classification of Diseases. RESULTS: The incidence of injuries was
      1.24 per 1000 hours of rugby training and 28.22 per 1000 hours of playing in
      matches. Low club position in rugby division (statistically significant, p<0.05),
      age from 25 to 34 years, forwards position in a team, being tackled, and
      beginning of autumn or spring season were identified as risk factors for
      injuries. The most frequent sites of injury were legs. The most frequent injuries
      were dislocations, strains and sprains of ankle and foot. CONCLUSIONS: The
      incidence of injuries in matches was more than two times higher than in more
      developed Scottish rugby, statistically positively correlating with the team
      position in division. There are no statistically significant differences in
      anthropometric characteristics, body composition and constitution of injured and
      uninjured players.

PMID- 11533573
TI  - Occult gastrointestinal bleeding in rugby player.
AB  - BACKGROUND: Local ischemia and mechanical trauma to hollow abdominal organs are
      quoted as a cause of gastrointestinal (GI) bleeding during and after long
      distance running. There are no data on athletes from rugby and other contact
      sports where mechanical trauma of the abdomen is frequent. METHODS: Occult
      bleeding in the stool of Croatian national rugby team players has been
      investigated during and after qualification match with Italy for the World Cup
      1999 on June 6th 1998 in Makarska, Croatia. One player with positive test was
      followed and examined in detail after the game. RESULTS: Among 11 Croatian
      players authors discovered one with a history of GI symptoms and one with
      conversion of negative to positive test for occult bleeding in stool after the
      match. The latter player had no GI symptoms or diseases, took no medications,
      played only 20 minutes in the match on forward position. Conversion has been
      found in the second stool sample after game (24 to 48 hours after game). The
      athlete was followed for 18 months. Persistent low values of hemoglobin,
      hematocrit and serum iron were revealed, as well as expressed hemorrhoids without
      signs of haemorrhage or inflammation. CONCLUSIONS: Lower incidence of GI bleeding
      among rugby players than among long distance runners minimize the importance of
      mechanical abdominal trauma in the etiology of GI bleeding during sports
      activity. Hemorrhoids are not quoted as a cause of GI bleeding after sport
      activity among athletes.

PMID- 11533574
TI  - Mobility impairment, muscle imbalance, muscle weakness, scapular asymmetry and
      shoulder injury in elite volleyball athletes.
AB  - BACKGROUND: The aim of this study was to evaluate the relationship between
      shoulder mobility, rotator muscles' strength and scapular symmetry, and shoulder
      injuries and/or pain in elite volleyball athletes. METHODS: An isokinetic
      shoulder muscle strength test, which was performed at speeds of 60/sec and
      180/sec, and shoulder mobility and scapula lateral slide tests were conducted
      bilaterally on 16 subjects, who represented the England elite volleyball players.
      The subjects also prospectively completed monthly questionnaires during the
      competition season to report on their shoulder condition. RESULTS: The results
      showed that the active range of shoulder internal rotation and concentric
      external rotators' strength in the dominant arm were significantly less, than in
      the non-dominant arms, but the internal rotators were significantly stronger in
      both concentric and eccentric tests at both testing speeds. Seven of 16 subjects
      indicated overt shoulder injury or pain during their training season, nine
      subjects had shoulder mobility impairment, seven had muscle imbalance, 13 had
      relative muscle weakness and five had scapular asymmetry. The association between
      shoulder muscle strength imbalance (eccentric external < concentric internal) of
      rotators in the dominant arm and shoulder injuries was statistically significant
      (Fisher's exact test, p<0.05). CONCLUSIONS: We conclude that rotator muscle
      strength imbalance may play an important role in shoulder injuries in high-level
      volleyball players.

PMID- 11533575
TI  - Validity of leg-to-leg bioelectrical impedance measurement in males.
AB  - BACKGROUND: This study determined the validity of the leg-to-leg bioelectrical
      impedance analysis (BIA) system (Tanita Body Fat Analyzer, TBF 105, Tanita
      Corporation of America, Inc., Arlington Heights, IL) in estimating body
      composition in males. METHODS:  EXPERIMENTAL DESIGN: Fat-free mass (FFM) was
      estimated using BIA and underwater weighing, and compared. SETTING: Subjects were
      recruited from the community. PARTICIPANTS: Heterogeneous group of males (N=192)
      was recruited, with a mean+/-SD age of 39.0+/-16.8 yrs; body mass index, 26.0+/
      4.0 kg/m2, percent body fat, 18.1+/-8.9 percent. MEASURES: Prior to BIA testing,
      subjects were required to adhere to standard BIA testing guidelines, and
      bioelectrical impedance was measured in subjects standing erect with bare feet on
      the analyzer's footpads, and wearing a swimsuit. Underwater weighing was
      conducted using standard procedures, with direct measurement of residual volume.
      RESULTS: A Bland-Altman plot of difference between FFM measured by underwater
      weighing and BIA versus average FFM by the two methods showed no systematic
      difference (mean difference, 0.07+/-3.5 kg). FFM was estimated at 66.3+/-8.6 kg
      with underwater weighing, and 66.2+/-7.7 kg with BIA (r=0.92, p<0.001; SEE 3.5
      kg). CONCLUSIONS: These data indicate that the leg-to-leg bioelectrical impedance
      system accurately assesses FFM in a heterogenous group of males when compared to
      underwater weighing.

PMID- 11533576
TI  - Localised hypertrophy of semimembranous muscle. A report of two cases in
      athletes.
AB  - We report two cases of localised hypertrophy of semimembranous muscle in young
      athletes diagnosed with ultrasonography, flow color-Doppler and MRI. The
      symptomatic case had the resolution of the pain after one month rest. At one year
      follow-up both cases are still asymptomatic, without any further increase of the
      hypertrophyc masses.

PMID- 11533577
TI  - Three cryptochromes are rhythmically expressed in Xenopus laevis retinal
      photoreceptors.
AB  - PURPOSE: To clone Xenopus laevis cryptochromes (crys) and to understand their
      role in the Xenopus retinal clock. METHODS: We designed degenerate PCR primers
      based on homology between mouse and human crys. DNA fragments generated from
      these PCR reactions were used to screen a Xenopus retinal cDNA library. Three
      independent clones were identified and sequenced. The temporal and spatial
      expression of these genes in retina were studied by Northern blot analysis and in
      situ hybridization. RESULTS: We cloned three cry homologs from Xenopus laevis
      retina. We named them xcry1, xcry2a, and xcry2b based on their high homology to
      the mouse crys. Sequence analysis shows that these Xenopus CRYs have more than
      85% identity to mouse CRYs at the amino acid level. Northern blot analysis
      demonstrated that all three xcrys are rhythmically expressed in the retina with
      peaks at different times of the day. The xcrys are expressed in a variety of
      tissues. In retina, they are expressed predominantly in photoreceptor cells.
      CONCLUSIONS: Our finding of cry expression in Xenopus photoreceptor cells further
      supports the idea of independent circadian oscillators being present in these
      cells. The sequence similarities to mouse crys suggest similar functions in the
      circadian clock. However, their distinct temporal expression patterns suggest
      some unique role for xCRY in the Xenopus retina.

PMID- 11533579
TI  - Differences between men and women in compliance with risk factor reduction:
      before and after coronary artery bypass surgery.
AB  - The purpose of this study was to determine whether a difference exists between
      genders in compliance to a heart-healthy lifestyle and whether the stress of
      coronary artery bypass graft (CABG) surgery caused one of the genders to become
      more compliant. A convenience sample of 30 men and 30 women who had CABG surgery
      at least 1 year earlier and were enrolled in a follow-up program through a
      cardiovascular surgeon's office were interviewed to assess coronary artery
      disease risk. The instrument used was the RISKO Heart Hazard Appraisal Tool.
      Preoperative records were also reviewed with the same tool to assess a person's
      preoperative risk. The research design used was 2 x 2 repeated measures. Data
      were analyzed with 2 x 2 repeated measures analysis of variance (ANOVA). Two
      findings were discovered. First, a statistically significant difference exists
      between men and women (F = 5.82 P =.019), with men scoring lower RISKO scores
      than women, indicating lower cardiovascular risk and better compliance to a
      healthy lifestyle, both before and after surgery. Second, a significant
      difference exists between preoperative and postoperative RISKO scores in the
      total population (F = 8.77 P =.004). Postoperative RISKO scores were lower,
      indicating an improvement in cardiovascular risk. The risk factors assessed are
      applicable to both heart disease and peripheral vascular disease.

PMID- 11533580
TI  - The Vascular Project: using data to improve processes and outcomes.
AB  - Fiscal accountability by health care providers has become a theme in health care
      delivery systems; however, evaluation of outcomes on the basis of cost alone may
      minimize the importance of patient needs and the quality of the care delivered.
      Mechanisms related to resource identification and allocation has to be driven by
      internal data and information systems that consider clinical, financial,
      administrative, and patient satisfaction data. This article will define
      processes, outcomes and outcomes measurement, and management. Various nursing
      sensitive outcomes will be presented and their establishment, tracking,
      interpretation, and effect on the delivery of patient care in a newly opened
      vascular unit will be highlighted.

PMID- 11533581
TI  - Raynaud's phenomenon.
AB  - Many persons are affected by the phenomenon known as Raynaud's. Raynaud's is
      classified in 2 ways-as Raynaud's disease or Raynaud's syndrome. Classification
      is based on the presence of associated conditions. Raynaud's is characterized by
      vasospasm-induced color changes of the fingers, toes, and ears. The fingers are
      most commonly affected. Studies involving cause, diagnosis, and treatment have
      been instituted with varied results. Diagnosis is primarily based on clinical
      symptoms involving digital color changes. Treatment is aimed at prevention of
      attacks and includes medication, stress reduction, and avoidance of
      vasoconstricting agents. Whether the phenomenon will develop into a more serious
      condition with which Raynaud's is associated is important. This article describes
      the etiology, pathophysiology, diagnosis, treatment, and nursing implications
      with regard to Raynaud's.

PMID- 11533582
TI  - Registered nurses' actual and perceived knowledge of diabetes mellitus.
AB  - This study assessed nurses' actual and perceived knowledge of diabetes. These
      nurses were employed in a community hospital and home healthcare agency. The
      Diabetes Basic Knowledge Test (DBKT) and the Diabetes Self-Report Tool (DSRT)
      were used to assess actual and perceived knowledge. Nurses' actual and perceived
      knowledge were positively correlated (r =.402, p <.0001). A mean score of 72.2%
      was obtained on the DBKT. The study findings raise questions about how competent
      nurses are in caring for patients with diabetes.

PMID- 11533583
TI  - The vascular nursing research priorities survey: an update.

PMID- 11533584
TI  - Digging for buried knowledge.

PMID- 11533585
TI  - The Southern Association for Vascular Surgery: The beginning.

PMID- 11533586
TI  - Rudolph Matas--how I remember him: an interview with Dr Michael E. DeBakey.

PMID- 11533587
TI  - The complex life of Rudolph Matas.

PMID- 11533588
TI  - Contribution of the Southern Association for Vascular Surgery to the scientific
      literature.
AB  - The Southern Association for Vascular Surgery (SAVS) has played a significant
      role in the development and evolution of vascular surgery. This study was
      designed to document the contribution to the scientific literature and to
      highlight the important publications from the annual meetings of the SAVS on its
      25th anniversary. A total of 413 (73%) of the 569 "free papers" presented at the
      SAVS Annual Meeting were published in journals that are identified in MEDLINE,
      and most (71%) were published in the Journal of Vascular Surgery.
      Carotid/cerebrovascular disease, leg ischemia, and basic considerations were the
      most common subject matters overall, although there has been a recent decrease in
      the percentage of articles about basic considerations and aortic aneurysms while
      there has been an increase in those about endovascular therapy, vascular
      laboratory/imaging, and visceral/renal artery disease. The 413 papers were cited
      a mean of 18 +/- 20 (+/- SD) times (range 0-143) with 32 papers cited more than
      39 times and 17 papers cited more than 59 times. A panel of three reviewers
      identified 42 significant articles, among which 8 were considered seminal by 2 of
      the 3 reviewers. The papers presented at the annual meeting of the SAVS have made
      a significant contribution to the scientific literature in terms of both quantity
      and quality. These efforts have laid the foundation for the next quarter century
      and have raised the level of expectation.

PMID- 11533589
TI  - Presidential address: A brief history of arterial blood flow--from Harvey and
      Newton to computational analysis.

PMID- 11533590
TI  - Aneurysmal expansion of the visceral patch after thoracoabdominal aortic
      replacement: an argument for limiting patch size?
AB  - INTRODUCTION: Thoracoabdominal aortic replacement requires visceral vessel
      revascularization and is usually performed with Crawford's inclusion technique or
      a large Carrel patch. This segment of retained native aorta may be prone to
      recurrent aneurysmal disease. We reviewed our experience with patients in whom
      aneurysmal expansion of the visceral patch was detected. METHODS: The records of
      107 patients undergoing thoracoabdominal aortic replacement operations performed
      or followed up at the Johns Hopkins Hospital between 1992 and 2000 were reviewed.
      All patients had visceral patches created for type II, III, or IV aneurysms.
      Visceral patches were considered aneurysmal if the maximal diameter of the aortic
      prosthesis and patch was 4.0 cm or more. RESULTS: Patch aneurysmal expansion
      (mean, 5.4 cm) was detected in eight patients (7.5%). All three women had
      connective tissue disorders (mean age, 36 years), and all five men had
      atherosclerotic disease (mean age, 73 years). Five patients were symptom free
      with their aneurysms detected by surveillance computed tomography scans; two
      patients had back pain prompting computed tomography scans; and one patient
      presented with an emergency patch rupture. Aneurysmal patches were successfully
      revised in three patients. Two patients died in the operating room, and three
      patch aneurysms (< 5 cm) are still being observed. The mean time to the detection
      of aneurysmal expansion was 6.5 years after the original operation. Therapy
      consisted of replacement of a segment of the thoracoabdominal aortic graft and
      refashioning a smaller patch, including only the visceral artery orifices with
      separate attachment of the left and possibly right renal artery. CONCLUSIONS:
      Although Crawford's inclusion method of visceral patch construction is generally
      durable, patients undergoing thoracoabdominal aortic replacement require yearly
      surveillance for the detection of aneurysmal expansion of the visceral patch. We
      recommend limiting visceral patch size at the original operation by routinely
      excluding the orifice of the left renal artery. Patients at high risk for
      recurrent aneurysmal expansion, such as those with connective tissue disorders,
      will benefit from creating small visceral patches and possibly implanting both
      renal arteries separately during the original operation.

PMID- 11533591
TI  - Expanded application of in situ replacement for prosthetic graft infection.
AB  - PURPOSE: The purpose of this study was to analyze the outcome of an
      individualized treatment algorithm for prosthetic graft infection, including the
      application of in situ graft replacement, based on clinical presentation, extent
      of graft infection, and microbiology. METHODS: There was a retrospective review
      (1991-2000) of 119 patients with 68 aortoiliofemoral or 51 extracavitary
      (infrainguinal, 19; axillofemoral, 16; femorofemoral, 16) prosthetic graft
      infections presenting more than 3 months (range, 3-136 months) after
      implantation/revision. The treatment algorithm consisted of graft excision with
      or without ex situ bypass grafts for patients presenting with sepsis or graft
      enteric erosion, whereas in situ replacement (autogenous vein, rifampin-bonded
      polyester, polytetrafluoroethylene [PTFE]) was used in patients with less
      virulent gram-positive graft infection, in particular infections caused by
      Staphylococcus epidermidis. Outcomes (death, limb loss, recurrent infection) were
      correlated with treatment type and infecting organism. RESULTS: In situ
      replacement was used in 52% of aortoiliofemoral (autogenous vein, 10; rifampin
      bonded polyester, 6; PTFE, 9) and 80% of extracavitary (autogenous vein, 26;
      PTFE, 9; rifampin, 6) graft infections. Total graft excision with ex situ bypass
      was performed in 34 patients, including 21 patients with graft-enteric
      erosion/fistula, with a 21% operative mortality and 9% amputation rate. In situ
      graft replacement was used to treat 76 graft infections with a 30-day operative
      mortality rate of 4% and an amputation rate of 2%. Graft excision alone was
      performed in nine patients with one 30-day death. Gram-positive cocci were the
      prevalent infecting organisms of both intracavitary (59% of isolates) and
      extracavitary (76% of isolates) graft infections. S epidermidis was the infecting
      organism in 40% of patients, accounting for the expanded application of in situ
      prosthetic replacement using a rifampin-bonded polyester or PTFE prosthesis.
      During the mean follow-up interval of 26 months, recurrent graft infection
      developed in 3% (1 of 34) of patients after conventional treatment, 3% (1 of 36)
      patients after in situ vein replacement, and 10% (4 of 40) patients after in situ
      prosthetic graft replacement (P >.05). Failure of in situ replacement procedures
      was the result of virulent and antibiotic-resistant bacterial strains.
      CONCLUSIONS: In situ replacement was a safe and durable option in most (64%)
      patients presenting with prosthetic graft infection. In situ replacement with a
      rifampin-bonded graft was effective for S epidermidis graft infection, but when
      the entire prosthesis is involved with either a biofilm or invasive perigraft
      infection, in situ autogenous vein replacement is preferred. Virulent graft
      infections presenting with sepsis, anastomotic dehiscence, or graft enteric
      fistula should continue to be treated with total graft excision, and if feasible,
      staged ex situ bypass graft.

PMID- 11533592
TI  - Endotension after endovascular aneurysm repair: the Ancure experience.
AB  - PURPOSE: The expansion of aneurysms after endovascular repair is a consequence of
      persistent sac pressure, usually resulting from an endoleak. Several authors have
      suggested that sac expansion can occur even in the absence of endoleak, referring
      to this phenomenon as endotension. This study undertakes a review of the largest
      US endograft trial data to better define the significance of aneurysm expansion
      in the absence of endoleak. METHODS: The core laboratory imaging database from
      the Ancure (Guidant) endovascular graft Phase I and Phase II trials approved by
      the Food and Drug Administration was reviewed with attention to aneurysm size and
      endoleak. Aneurysm size was measured with standardized two-dimensional computed
      tomography (CT) scan at the area of largest initial aneurysm diameter. Endoleak
      was detected with CT scans, color duplex ultrasound scans, and angiography in
      selected cases. Patients were evaluated at baseline, 3 months, 6 months, 12
      months, and every 12 months thereafter. An endograft was classified as leaking if
      any endoleak was detected with any modality at any time point. RESULTS: A total
      of 658 patients were entered into these protocols and the data submitted to the
      core laboratory. A control group of 120 conventional aortic patients and a group
      of 62 without baseline CT data were excluded from further analysis. Of the
      remaining 476 patients, 144 (60 tube, 60 bifurcated, and 24 mono-iliac) were free
      of endoleak at all intervals and had baseline CT measurements to allow
      comparison. Overall, the average size decrease in this nonleaking group was 9.9
      +/- 9.4 mm (range, -50.6-11.1 mm) at a mean follow-up of 23.3 months. Evaluation
      for overall aneurysm expansion revealed 17 patients who had an increase of 2.3 +/
      2.9 mm (range, 0.3-11.1 mm) at a mean follow-up of 14.1 months. Only two
      patients without evidence of endoleak exhibited growth of more than 5 mm at
      maximum follow-up (7.6 mm at 12 months and 11.1 mm at 36 months). Additional
      analysis of sealed endoleaks and late endoleaks failed to demonstrate any group
      with expansion in the absence of detectable endoleak. CONCLUSIONS: Endotension
      appears to be rare in this large series of prospectively evaluated endografts.
      From this review, endotension seems more likely to represent missed endoleak than
      true aneurysm expansion in the absence of perigraft flow.

PMID- 11533593
TI  - Remote superficial femoral artery endarterectomy: Multicenter medium-term
      results.
AB  - OBJECTIVE: The results of percutaneous transluminal angioplasty, atherectomy, and
      laser angioplasty for the treatment of long-segment (>10 cm) superficial femoral
      artery (SFA) occlusive disease have proved disappointing. Remote superficial
      femoral artery endarterectomy (RSFAE) is a minimally invasive procedure,
      performed through a single limited groin incision that may offer patency rates
      comparable with those of above-knee femoropopliteal (AKFP) bypass graft. In this
      retrospective multicenter study the medium-term results of RSFAE are examined.
      METHODS: Sixty patients were included in this study. Indications for the
      procedure were claudication in 52 patients and limb salvage in eight patients.
      RSFAE was performed with the MollRing Cutter device through a femoral
      arteriotomy. The distal "flap" of atheroma was anchored by balloon/stent
      angioplasty through the femoral arteriotomy. All patients underwent a follow-up
      examination with serial color flow ultrasound scanning. RESULTS: Ten patients
      with heavily calcified SFAs failed as "intentions to treat"; these patients
      underwent AKFP bypass grafting. The mean length of the endarterectomized SFAs was
      22.3 cm (range, 8-37 cm). The primary cumulative patency rate by means of life
      table analysis was 61.4% +/- 9% (SE), (mean, 12.9 months; range, 3-36 months).
      During follow-up, percutaneous transluminal angioplasty was necessary in 14
      patients, for a primary-assisted patency rate of 82.6% +/- 8%. The locations of
      the restenoses after RSFAE were evenly distributed along the endarterectomized
      SFAs. There were no deaths and one wound complication (hematoma), and the mean
      hospital length of stay was 1.4 days +/- 0.8 days. CONCLUSIONS: RSFAE is a safe
      and moderately durable procedure. If long-term patency rates are similar to those
      of AKFP bypass graft, RSFAE may prove to be a minimally invasive adjunct for the
      treatment of SFA occlusive disease that will lower operative morbidity, reduce
      hospital LOS, and shorten recuperation.

PMID- 11533594
TI  - The durability of endoscopic saphenous vein grafts: a 5-year observational study.
AB  - BACKGROUND: Endoscopic saphenous vein harvest has been explored as a minimally
      invasive alternative to a long continuous leg incision for removal of the greater
      saphenous vein. The endoscopic technique uses limited incisions (2-4) with
      extended "skin bridges" and videoscopic equipment for the dissection and removal
      of the greater saphenous vein. This study was undertaken to evaluate the long
      term durability of saphenous vein grafts harvested by an endoscopic technique and
      used for lower extremity arterial revascularization. METHODS: All patients who
      underwent endoscopic saphenous vein harvesting for lower extremity arterial
      bypass grafting were prospectively followed for graft patency and risk factors.
      Grafts were surveyed with serial duplex scans at 3- to 6-month intervals over
      this 5-year study. Life-table methods were used to assess graft survival. A
      computerized registry and medical records were reviewed to determine graft
      patency and patient survival. RESULTS: From September 1994 to August 2000, 164
      lower extremity arterial saphenous vein grafts harvested by an endoscopic
      technique were used for lower extremity arterial bypass grafting in 150 patients.
      The patient population included 111 males (75%) and 112 smokers (75%), but also
      included a high-risk cohort of 65 diabetic patients (43%) and 15 patients
      undergoing dialysis/renal transplant (10%). Twenty-eight patients (19%) died
      within the study period. With life-table methods, 1-, 3-, and 5-year secondary
      patency rates were 85% (+/- 3.2%), 74% (+/- 5.7%), and 68% (+/- 11.6%). Of the 30
      failed grafts, 7 (4%) failed in the first month related to inadequate runoff (4),
      cardiac instability (2), and an additional surgical procedure (1). Twenty-three
      grafts (14%) failed between 1 and 42 months. Twenty-two (16%) of these 134 patent
      grafts underwent a second procedure to maintain patency (13 as primary-assisted
      patency and 9 as secondary patency). CONCLUSIONS: Endoscopic saphenous vein
      harvest for lower extremity arterial reconstruction provides a satisfactory
      conduit for lower extremity bypass grafting. Although increased manipulation from
      this limited access technique may incite an injury response in the vein, these
      vein grafts can maintain an adequate patency for lower extremity bypass grafting.

PMID- 11533595
TI  - External iliac and common iliac artery angioplasty and stenting in men and women.
AB  - OBJECTIVE: The effect of anatomic location of stent placement on the outcome of
      iliac artery angioplasty and stenting is not defined. Analyses of patency rates
      of external iliac artery (EIA) and common iliac artery (CIA) stents have provided
      conflicting results and have not considered men and women independently. The
      purpose of this study was to estimate the influence of the anatomic location of
      stenting on the outcome of iliac angioplasty and stent placement in both men and
      women. METHODS: From 1995 to 1999, 247 iliac angioplasty and stent placement
      procedures (303 stents) were performed in 67 women and 122 men, and all were
      included in a retrospective cohort study. The criteria prepared by the Ad Hoc
      Committee on Reporting Standards (Society for Vascular Surgery/International
      Society for Cardiovascular Surgery) were followed. The TransAtlantic Inter
      Society Consensus classification was used to characterize the type of iliac
      lesions. Both univariate (Kaplan-Meier [KM]) and multivariate analyses (Cox
      proportional hazards model) were used to determine the association among the
      variables, cumulative patency, limb salvage, and survival. RESULTS: Indications
      for iliac angioplasty with stenting were disabling claudication (65%), limb
      salvage (33%), and blue toe syndrome (2%). Primary stenting was performed in 103
      procedures (42%). Stents were placed selectively after iliac angioplasty mainly
      for residual stenosis or pressure gradient (43%). Patients with EIA stents, as
      compared with those who had CIA stents, had more extensive lesions (TransAtlantic
      Inter-Society Consensus type C lesions), poorer runoff, smaller vessel size, and
      less frequency of hyperlipidemia (P <.05). Primary patency rates at 1, 3, and 5
      years were 76%, 56%, and 56%, respectively, for patients with EIA stents and 92%,
      85%, and 76%, respectively, for those with CIA stents. Although overall primary
      patency rates were significantly decreased in patients with EIA lesions (KM, log
      rank test, P =.001), stratified analyses revealed that women with EIA stents had
      the poorest outcome, with 61%, 47%, and 23% primary patency rates at 1, 3, and 5
      years, respectively, (KM, log-rank test, P <.001). Cox regression analysis
      identified EIA stenting (relative risk, 4.3; 95% CI, 2.3-7.9; P <.001) as an
      independent predictor of decreased primary patency in women but not in men.
      CONCLUSIONS: Women undergoing EIA angioplasty with stent placement have
      significantly reduced primary patency rates. Despite initial technical success,
      these patients are at increased risk of long-term failure and might require
      subsequent procedures to obtain clinical success. Conversely, men undergoing EIA
      stenting have a more favorable outcome than women.

PMID- 11533596
TI  - Enoxaparin treatment in high-risk trauma patients limits the utility of
      surveillance venous duplex scanning.
AB  - OBJECTIVE: The value of surveillance venous duplex scanning for detecting
      unsuspected deep venous thrombosis (DVT) in trauma patients who are receiving
      enoxaparin prophylaxis is open to question. This study was undertaken to
      determine whether enoxaparin reduced the clinical utility of surveillance
      scanning and whether management of these patients was altered by findings of the
      scans. METHODS: The medical records of trauma patients who met defined criteria
      for high DVT risk, admitted during 30 consecutive months, were reviewed. These
      patients received enoxaparin 30 mg every 12 hours for the duration of their
      admissions. Per protocol, surveillance lower extremity venous duplex scans were
      performed within 72 hours of enoxaparin administration and then weekly until
      patients were discharged from the hospital. The records were reviewed for
      thromboembolic events (DVT or pulmonary embolism [PE]), patient location and
      ambulatory status, therapeutic interventions (systemic anticoagulation, vena cava
      filter), and complications of enoxaparin therapy. RESULTS: A total 241 patients
      underwent 513 venous duplex examinations (1-13 per patient). Eight patients had
      DVT on the initial scan; seven of these patients were asymptomatic. Five were
      treated with anticoagulation and/or vena cava filter placement. Of the 233
      patients with initially negative duplex scan results, five patients (2%)
      developed clinically unsuspected lower extremity DVT while hospitalized. All of
      these five patients were in an intensive care unit. Three of the five patients
      had no change in treatment. Two of the five underwent anticoagulation, and one
      vena cava filter was placed. PE occurred in two hospitalized patients, one of
      whom was ambulatory, with negative duplex scan results. After hospital discharge,
      six other patients had symptomatic DVT or PE despite in-hospital scans with
      negative results. Complications associated with enoxaparin included hemorrhage
      (2) and thrombocytopenia (8). CONCLUSIONS: After initial negative scan results,
      repeat surveillance duplex scanning during hospitalization detected a low
      incidence (2%) of DVT in high-risk patients. Furthermore, the detection of
      unsuspected DVT altered the clinical management of less than 1% of the patients
      tested. Thus, after a venous duplex scan with negative results and initiation of
      enoxaparin prophylaxis, subsequent surveillance duplex examinations are not
      warranted in asymptomatic trauma patients.

PMID- 11533597
TI  - Durability of eversion carotid endarterectomy: comparison with primary closure
      and carotid patch angioplasty.
AB  - OBJECTIVES: Despite numerous studies in which various methods for arteriotomy
      closure after carotid endarterectomy (CEA) have been addressed, the optimum
      surgical technique to reduce complications and late carotid restenosis has yet to
      be firmly established. The purpose of this study was to prospectively compare the
      results of the eversion CEA technique with those of conventional CEA with either
      primary closure or carotid patch angioplasty, and to determine under clinical
      conditions whether eversion CEA influences the results and restenosis rate.
      PATIENTS AND METHODS: Over a 3-year period, 322 CEAs performed on 296 consecutive
      patients were concurrently evaluated. This study included 118 eversion CEAs, 97
      CEAs with primary closure, and 107 CEAs with patch angioplasty. There were no
      differences in demographics, in surgical indications, or in the severity of
      carotid disease (not significant [NS]). The choice of CEA technique was not
      randomized because of technical considerations and surgeon preference. After
      entry into the protocol, no patients were excluded or withdrawn. Carotid
      restenosis was defined as a > 60% lumen reduction at the CEA site with
      established duplex ultrasonography criteria. RESULTS: The mean operative time for
      eversion CEA was 31 minutes, for CEA-primary closure it was 39 minutes, and for
      CEA-patch angioplasty it was 46 minutes (P <.01). The operative mortality rate
      for eversion CEA was 0.8% (1 patient), for CEA-primary closure it was 1.0% (1
      patient), and for CEA-patch angioplasty it was 2.8% (3 patients) (NS). The
      postoperative stroke rate was 0.8% after eversion CEA, 1.0% after CEA-primary
      closure, and 2.8% after CEA-patch angioplasty (NS). The combined stroke and death
      rate in each group was thus 0.8% for eversion CEA (1 stroke-death), 1% for CEA
      with primary closure (1 stroke-death), and 5% for CEA with patch angioplasty (1
      stroke-death, 2 fatal myocardial infarctions, and 2 nonfatal strokes) (NS).
      Transient ischemic attacks occurred in 2.5% after eversion CEA, in 5.2% after CEA
      primary closure, and in 2.9% with CEA-patch angioplasty (NS). The mean clinical
      follow-up for all three groups was 23 months (range, 6-42 months) (NS). The
      restenosis rate was 1.7% after eversion CEA, 9.3% after CEA-primary closure, and
      6.5% after CEA-patch angioplasty (P <.05). CONCLUSIONS: This prospective,
      nonrandomized clinical study indicates that eversion CEA is an effective surgical
      option comparable to conventional CEA with either primary arteriotomy closure or
      carotid patch angioplasty. No differences were found between eversion CEA and
      these more widely accepted CEA closure techniques with respect to operative
      morbidity and mortality. These data indicate, however, that eversion CEA has a
      lower restenosis rate than conventional CEA closure techniques and thus superior
      long-term durability.

PMID- 11533598
TI  - A clinical comparison of pneumatic compression devices: the basis for selection.
AB  - PURPOSE: The five pneumatic compression devices (PCDs) that are marketed provide
      mechanical protection from deep venous thrombosis (DVT). They differ with respect
      to patterns of compression and the length of the sleeve. Evidence linking
      differences to clinical outcomes is lacking. Our purpose was twofold: to evaluate
      each of the marketed PCDs with respect to effectiveness, compliance, and patient
      and nursing satisfaction and to determine whether there is a clinical basis for
      the selection of one device over another. METHODS: Each of the marketed devices
      was used exclusively for a 4-week period. Patients participated in an evaluation
      including venous duplex ultrasound scan, DVT risk assessment, and device
      evaluation. Vascular laboratory records were used to document DVT. Compliance was
      measured by meters installed on all pumps. A ranking matrix was stratified by
      compression pattern: rapid graduated sequential compression, graduated
      compression, and intermittent compression, and each device was rated by patients
      and nurses. RESULTS: The PCDs were used in 1350 cases with a DVT rate of 3.5%
      ranging from 2% to 9.8% depending on the method of compression. Patients with DVT
      were older (58 vs 54 years), had better compliance (67% vs 50%), and had more
      compression days (11 vs 7.2). When thigh-length sleeves were used, a greater
      proportion of DVT occurred in the proximal segments (71%) as compared with the
      number of proximal DVT when the calf-length devices were used (52%; P =.21).
      Devices W, X, and Y had comparable rates of DVT, which were lower than those for
      V and Z. Compression device W, [correction] with calf and thigh sleeves, achieved
      the best overall ranking largely because of high scores for patient and nurse
      satisfaction. CONCLUSION: Our data appear at odds with commonly held beliefs. We
      were unable to show a difference in DVT incidence based on the length of the
      device or the method of compression. Randomized studies are needed to confirm our
      findings and evaluate hypotheses derived from this study.

PMID- 11533599
TI  - Multicenter evaluation of a polyurethaneurea vascular access graft as compared
      with the expanded polytetrafluoroethylene vascular access graft in hemodialysis
      applications.
AB  - OBJECTIVES: The purpose of this study was to compare in a randomized,
      prospective, and controlled study, the performance of a multilayered, self
      sealing polyurethane vascular access graft (PVAG) and expanded
      polytetrafluoroethylene (ePTFE) vascular access grafts in hemodialysis
      applications. Performance measures included graft survival, complications, time
      to early cannulation, and hemostasis times after cannulation. STUDY DESIGN: A
      total of 142 patients were randomized equally to receive one of the two grafts
      after meeting all eligibility requirements. All patients were followed up
      prospectively to 12 months or to the end of secondary patency. Specifically, this
      study documented the performance of the PVAG and ePTFE grafts by determining the
      patencies and complications for both grafts. RESULTS: Patient characteristics
      between the two groups were similar with respect to risk factors and demographic
      characteristics (P >.05). Life-table patencies from the date of first dialysis
      were primary patency: PVAG 55% versus ePTFE 47% (6 months) and PVAG 44% versus
      ePTFE 36% (12 months) and secondary patency: PVAG 87% versus ePTFE 90% (6 months)
      and PVAG 78% versus ePTFE 80% (12 months). None of these differences were
      significant (P >.05). Both primary and secondary patencies were also not
      significantly different when the date of implantation was the starting point.
      Adverse events and complications were similar for the two groups, except the PVAG
      group had a higher incidence of technical complications manifested by graft
      kinking when compared with the control cohort (P <.05). Additionally, there was
      no significant difference in complication rates between these two groups with
      regard to infection and bleeding. When the time to hemostasis after cannulation
      was compared at 5minutes or less, there were more PVAG cannulation sites that
      achieved hemostasis compared with ePTFE sites, and this difference was
      significant (P <.0001). When time to first dialysis access was compared between
      the two grafts, 53.9% of all PVAG grafts were cannulated before 9 days versus
      none with the ePTFE grafts (P <.001). However, long-term graft survival was not
      significantly different when PVAG patients were stratified into early (< 9 days)
      and the late access (9 >/= days) groups (P =.29). CONCLUSIONS: The PVAG graft
      allows for early access without compromising long-term performance. Both PVAG and
      standard ePTFE grafts have similar long-term outcomes, despite early access with
      the PVAG vascular access grafts.

PMID- 11533600
TI  - Folate supplementation inhibits intimal hyperplasia induced by a high
      homocysteine diet in a rat carotid endarterectomy model.
AB  - OBJECTIVE: Hyperhomocysteinemia has been implicated as a causative factor in
      intimal hyperplasia development. The addition of dietary folate in a
      hyperhomocysteinemia, carotid endarterectomy rat model is postulated to decrease
      plasma homocysteine levels and, in turn, reduce post-carotid endarterectomy
      intimal hyperplasia. METHODS: Each rat was fed one of six diets: (1) lab chow
      with no folate (n = 7), (2) lab chow with 10 mg/kg folate added (n = 3), (3) lab
      chow with 25 mg/kg folate added (n = 3), (4) a homocysteine diet with no folate
      (n = 7), (5) a homocysteine diet with 10 mg/kg folate added (n = 5), or (6)
      homocysteine diet with 25 mg/kg folate added (n = 5). Each rat then underwent an
      open carotid endarterectomy. In 2 weeks, intimal hyperplasia in the carotid
      artery was measured. Plasma homocysteine and folate levels were measured.
      RESULTS: Plasma folate levels rose with folate administration. Plasma
      homocysteine in the lab chow group was 5.4 +/- 0.5 micromol/L and did not change
      with the addition of folate. In the homocysteine diet group, plasma homocysteine
      rose 10-fold over the lab chow group (51.9 +/- 6.5 vs 5.4 +/- 0.5, micromol/L, P
      <.0001). In the group fed a homocysteine diet with 10 mg/kg folate added, a
      significant decrease in plasma homocysteine was observed (17.5 +/- 8.5 vs 51.9 +/
      6.5, micromol/L, P =.0003). In the group fed a homocysteine diet with 25 mg/kg
      folate added, plasma homocysteine levels were further reduced to levels seen in
      the lab chow group (12.6 +/- 2.6 vs 5.4 +/- 0.5, micromol/L, P = not
      significant). The relationship between plasma folate and homocysteine was inverse
      (R = 0.39, P =.0036). Luminal stenosis due to intimal hyperplasia was minimal in
      lab chow groups and unaffected by folate. The homocysteine diet group
      demonstrated post-carotid endarterectomy luminal stenosis due to intimal
      hyperplasia (60.9% +/- 9.2%). In the group fed a homocysteine diet with 10 mg/kg
      folate added, intimal hyperplasia was reduced, compared with the homocysteine
      diet group (32.6% +/- 7.4% vs 60.9% +/- 9.2%, P =.009). In the group fed a
      homocysteine diet with 25 mg/kg folate added, intimal hyperplasia was reduced to
      lab chow group levels (10.8% +/- 0.8% vs 4.8% +/- 1.0%, P = not significant) and
      was reduced, compared with the group fed a homocysteine diet with 10 mg/kg folate
      added. CONCLUSION: The use of folate in this hyperhomocysteinemia carotid
      endarterectomy model and the resultant attenuation of plasma homocysteine
      elevation and intimal hyperplasia development lend strong support to homocysteine
      being an independent etiologic factor in post-carotid endarterectomy intimal
      hyperplasia.

PMID- 11533601
TI  - An adenosine A2A agonist, ATL-146e, reduces paralysis and apoptosis during rabbit
      spinal cord reperfusion.
AB  - BACKGROUND: We hypothesized that systemic ATL-146e, an adenosine A(2A) agonist,
      would decrease spinal cord reperfusion inflammatory stress and inhibit apoptosis
      and that these effects would correlate with improved neurologic functional
      outcome. METHODS: Thirty rabbits underwent cross-clamping of the infrarenal aorta
      for 45 minutes. One group of animals (n = 14) received 0.06 microg/kg per minute
      of ATL-146e infused intravenously for 3 hours, beginning 15 minutes before
      reperfusion. A second group of animals (n = 16) underwent spinal cord ischemia
      with saline vehicle alone and served as ischemic controls. Animals (n = 9, 11)
      from each group survived for 48 hours and assessed for neurologic impairment with
      the Tarlov (0-5) scoring system. Four animals from each group were humanely
      killed at the end of the 3-hour treatment period, and the remainder killed after
      48 hours' survival. In all animals, lumbar spinal cord tissue specimens were
      frozen for subsequent Western blot analysis of heat shock protein 70 (HSP 70),
      and for the p85 fragment of poly (ADP-ribose) polymerase (PARP). Neuronal
      viability indices were determined at 48 hours with hematoxylin and eosin
      staining. RESULTS: There was improvement in neurologic function in rabbits
      receiving ATL-146e (P <.001) compared with ischemic controls. At the end of the 3
      hour treatment period there was a 46% (P <.05) decrease in HSP 70 expression in
      the ATL-146e group compared with the control group, but no difference in PARP
      expression. At 48 hours, there was no difference between control and ATL-146e
      groups in HSP 70 expression, but there was a 65% (P <.05) reduction in PARP in
      the spinal cords of animals that had received ATL-146e. There was a significant
      improvement in neuronal viability indices in animals receiving ATL-146e compared
      with ischemic controls (P <.05). CONCLUSIONS: Systemic ATL-146e infusion during
      reperfusion after spinal cord ischemia results in preservation of hindlimb motor
      function. There is evidence of decreased spinal cord inflammatory stress
      immediately after treatment with ATL-146e as indicated by reduced HSP 70
      induction. Treatment with ATL-146e is associated with a reduction in neuronal
      apoptosis as suggested by a substantial decrease in the fragmentation of PARP at
      48 hours. These results suggest that inflammation during reperfusion and
      subsequent apoptosis contribute to paralysis after restoration of blood flow to
      the ischemic spinal cord.

PMID- 11533602
TI  - Administration of adenoviral vectors induces gangrene in acutely ischemic rat
      hindlimbs: role of capsid protein-induced inflammation.
AB  - PURPOSE: The initial purpose of this study was to determine the effects of
      intravascular adenoviral vector-mediated gene transfer of endothelial nitric
      oxide synthase (AdeNOS) on experimental hindlimb ischemia in the rat.
      Unexpectedly, administration of AdeNOS immediately after induction of acute limb
      ischemia led to limb gangrene. We subsequently sought to define the molecular
      mechanisms responsible for this unusual effect and to devise adenoviral gene
      transfer strategies to prevent the development of gangrene in acutely ischemic
      limbs. METHODS: Phosphate-buffered saline or adenoviral vectors containing the
      bovine endothelial nitric oxide synthase gene (AdeNOS) or no transgene (Ad-E1)
      were injected intra-arterially into the hindlimb of a rat under vascular
      isolation immediately after surgical induction of severe ischemia. Hematoxylin
      and eosin staining was performed on muscle sections to evaluate inflammation. A
      separate group of animals was injected with an adenovirus containing a
      nontranscribable genome, treated with cyclosporine, or received delayed
      administration of the adenoviral vector. Gene expression after delayed adenoviral
      gene transfer was assessed with immunohistochemistry, Western blotting, and
      nitric oxide synthase (NOS) activity assay. RESULTS: Both AdeNOS and Ad-E1 caused
      gangrene of the entire hindlimb within 12 days in a dose-dependent manner, at a
      threshold concentration of 1 x 10(9) plaque-forming unit/mL. Adenoviral delivery
      was associated with more inflammation and edema compared with phosphate-buffered
      saline histologically. Inactivation of adenoviral DNA transcription did not
      affect induction of gangrene. However, gangrene was prevented by concurrent
      immunosuppression with cyclosporine or delayed administration of the vector.
      Delayed administration allowed adenoviral gene expression as determined by
      immunohistochemistry, NOS protein levels, and an assay of NOS enzyme activity.
      CONCLUSION: Intra-arterial administration of adenoviral vectors, under vascular
      isolation, immediately after induction of acute ischemia causes inflammation and
      subsequent limb gangrene. The inflammatory response is unrelated to the
      expression of the recombinant transgene or the adenoviral genome and is likely
      due to the adenoviral capsid proteins. However, administration of cyclosporine or
      delayed injection of the adenoviral vector is a method that can be used for
      adenoviral mediated gene transfer in limb ischemia.

PMID- 11533603
TI  - Early experience with the bifurcated Excluder endoprosthesis for treatment of the
      abdominal aortic aneurysm.
AB  - PURPOSE: This report describes our initial experience with the modular,
      bifurcated Excluder endoprosthesis and its safety and efficacy in the primary
      endovascular repair of infrarenal abdominal aortic aneurysms (AAAs). METHODS:
      AAAs (mean diameter, 58.2 +/- 14.3 mm) were repaired in 19 patients with this
      device between March 1999 and January 2000. The mean age of patients was 71.8 +/-
      8.4 years (range, 57-86 years). This modular device was inserted through an 18F
      introducer sheath placed in one femoral artery, and the contralateral artery was
      cannulated with a 12F introducer sheath. All procedures were performed in a
      standard operating room with angiographic capabilities. RESULTS: Endograft
      deployment was successful in all patients. The average surgical time was 135 +/-
      37 minutes, with a mean blood loss of 229 +/- 138 mL. In eight patients, the use
      of either aortic or iliac extenders was required for enhanced sealing or
      additional length. An external iliac artery dissection occurring at the time of
      endograft insertion was successfully treated with a Wallstent. Type II leaks
      initially found to be present by means of intraoperative completion angiography
      had spontaneously thrombosed by the 1-month follow-up computed tomography scan.
      There was one perioperative death (5.3%). Complications included superficial
      wound infections (n = 3) and a nonfatal myocardial infarction (n = 1). The mean
      length of hospital stay was 2.9 +/- 1.2 days, and only six patients required
      intensive care. Endoleaks were seen in four patients (21%) by means of the 30-day
      computed tomography scan; three of these endoleaks had spontaneously sealed at
      the time of the 6-month follow-up examination (5.5% 6-month endoleak rate).
      Aneurysm size did not increase in the patients with leaks. CONCLUSION: The
      Excluder endoprosthesis was an effective means of excluding an infrarenal AAA
      from the systemic circulation in this selected group of patients. The smaller
      sheath sizes may increase the pool of potential candidates. Further study of this
      device is warranted, and continued assessment of the long-term durability of the
      device will be necessary.

PMID- 11533604
TI  - Endovascular repair of para-anastomotic aneurysms of the aorta and iliac
      arteries: preferred treatment for a complex problem.
AB  - PURPOSE: Standard surgical repair of para-anastamotic aneurysms (PAAs) of the
      abdominal and thoracic aorta and the iliac arteries has been associated with high
      morbidity and mortality rates. We reviewed our continuing experience with
      endovascular repair of these lesions to determine whether this approach is
      favorable and durable. METHODS: All patients with PAAs of the aorta or iliac
      arteries who underwent endovascular treatment of their lesions between August
      1993 and July 1999 were prospectively followed up, and data on age, previous
      aortic pathology and surgery, size of PAA, time to diagnosis, and symptoms at
      presentation were recorded. Preoperative, intraoperative, and postoperative
      imaging studies were analyzed. All patients had endovascular stent-grafts placed
      under digital fluoroscopic guidance in the operating room. Data on intraoperative
      and postoperative complications, mortality, and endoleaks were reviewed. RESULTS:
      From August 1993 to July 1999, 28 patients (20 men, 8 women) had 35 PAAs of the
      aorta or iliac arteries. There were 5 thoracic aortic, 12 abdominal aortic, and
      18 iliac artery PAAs. Three patients had a contained rupture of their PAA. All
      patients who had originally undergone reconstruction for occlusive disease had
      lesions consistent with false aneurysms, whereas 73% of the aortic or iliac PAAs
      in patients originally treated for aneurysm disease appeared to be true
      aneurysms. Thirty-four of 35 PAAs were successfully excluded with stent-grafts
      (97%). There was one death at 30 days (3.6%) in a patient who was successfully
      treated endovascularly for a contained rupture of a thoracic PAA. There were four
      major postoperative complications (14.2%) in the 28 patients who were treated.
      One patient had continued perfusion of a thoracic aortic PAA (type I endoleak).
      The in-hospital length of stay after endovascular repair of PAA was 4 days
      (range, 1-18 days). The mean follow-up period was 21 months (range, 1-68 months).
      CONCLUSION: Endovascular repair of aortic and iliac artery PAAs is technically
      feasible and provides a high rate of lesion exclusion. Morbidity and mortality
      rates appear lower than those reported for open surgical repair. These patients
      can typically be discharged by the second postoperative day. Endovascular therapy
      for stable ruptured PAAs can be successfully performed and should be considered
      as an option only when appropriate devices and expertise are available. For
      uncomplicated PAAs of the aorta and iliac arteries, endovascular therapy may be
      more favorable than surgical repair.

PMID- 11533605
TI  - Aneurysmal degeneration of the aorta after stent-graft repair of acute aortic
      dissection.
AB  - PURPOSE: Stent-graft repair of acute aortic dissection has only recently begun,
      and the true efficacy and safety of this technique have not yet been clarified.
      In this report, we describe a significant, previously unreported complication
      following stent-graft repair of acute aortic dissection. MATERIALS AND METHODS:
      Fourteen patients with acute aortic dissection underwent stent-graft repair. All
      of the entry tears were located in the descending thoracic aorta. Five patients
      had type A aortic dissection, and nine patients had type B aortic dissection. The
      entry tears were closed with stent-grafts, which were fabricated from expanded
      polytetrafluoroethylene and Z-stents. RESULTS: Stent-graft placement was
      successfully performed without any complications in all patients. Entry closure
      was achieved in 13 (93%) of 14 patients. The mean follow-up period was 18 months
      (range, 9 days to 36 months). During this period, four patients had saccular
      aneurysms in the proximal descending thoracic aorta. A saccular aneurysm was
      noted during a mean follow-up period of 63 days (range, 38-99 days). Two of these
      patients were treated with stent-grafts. Conventional surgical repair is planned
      in one patient. The other patient is being treated with conservative management.
      CONCLUSIONS: Stent-graft repair is a technically feasible and effective method
      for the treatment of acute aortic dissection in selected patients. However,
      careful follow-up is mandatory to check for the development of saccular
      aneurysms.

PMID- 11533606
TI  - Pressure measurements in closed aneurysmal sac during abdominal aortic aneurysm
      resection.
AB  - PURPOSE: This study determined the relationship between closed aneurysmal sac
      pressure (ASP) and mean blood pressure (BP) during open abdominal aortic aneurysm
      (AAA) resection and evaluated the contribution of inferior mesenteric and lumbar
      artery blood flow to ASP after proximal and distal clamping. METHODS: We measured
      ASP after proximal and distal clamping by placing an 18-gauge needle connected to
      a BP transducer into the excluded aneurysmal sac in 25 consecutive patients from
      April 1999 to August 2000. Simultaneous measurement of the mean systemic BP was
      also recorded. The ratio of ASP to mean BP in relation to the number of actively
      bleeding lumbar arteries (N-LA), diameter of the AAA (D-Cm), and volume of the
      thrombus in the AAA (Vol-TA) were recorded. RESULTS: The mean ASP was 43.32 +/-
      15.19 mm Hg, with an ASP to mean BP ratio of 0.47 +/- 0.15. The N-LA in the
      closed aneurysmal sac ranged from 0 to 6 (mean, 3.4 +/- 1.78). The D-Cm as
      determined by means of computed tomography (CT) scan of the aorta ranged from 5
      to 8 cm in its largest anteroposterior/transverse diameter. The average Vol-TA
      was 6.15 +/- 4.49 mL. Inferior mesenteric artery blood flow contributed to ASP in
      three patients (12%). There was no correlation between ASP to mean BP ratios and
      the N-LA (P =.127), D-Cm (P =.882), or Vol-TA (P =.252). CONCLUSION: Closed ASP
      and ASP ratios are highly variable and do not correlate with N-LA, D-Cm, or the
      Vol-TA.

PMID- 11533607
TI  - Results of endovascular superficial femoral endarterectomy.
AB  - BACKGROUND: Endovascular superficial femoral artery (SFA) endarterectomy with a
      ring stripper/cutter and distal stenting has been suggested to have a patency
      comparable with above-knee bypass surgery. We report our initial experience with
      this technique. METHODS: Seventeen patients (13 men and 4 women; mean age, 64
      years) with SFA occlusion and above-knee popliteal reconstitution underwent
      attempted remote endarterectomy with a ring cutter system combined with primary
      stenting of the distal end point. Analysis was performed in a prospective manner
      with patency rates determined by Kaplan-Meier life-table analysis. RESULTS: The
      indication for operation was claudication in 8 patients, rest pain in 6, and
      tissue loss in 3. Initial technical success was achieved in 11 patients (65%).
      Reasons for technical failure included SFA perforation (4), inability to traverse
      a calcified/diseased segment (1), and inability to retract/remove the ring cutter
      (1). Life-table analysis of all patients revealed a primary patency at 1 year of
      26% +/- 11%. Primary-assisted patency was 38% +/- 12% at 1 year, with 59% of
      patients ultimately requiring surgical bypass grafting. In patients in whom
      initial technical success was achieved, the 1-year primary and primary-assisted
      patency rates were 40% and 59%, respectively. There were four reocclusions
      requiring surgical revascularization with below-knee popliteal (2) or tibial (2)
      bypass grafting, 1 symptomatic restenosis requiring repeat angioplasty, and 1
      symptomatic restenosis treated conservatively. CONCLUSION: The results of
      endovascular SFA endarterectomy were disappointing, with technical success in
      less than two thirds of patients and a 1-year primary patency of only 26%. Remote
      SFA endarterectomy appears less effective than above-knee femoropopliteal bypass
      grafting, and after early failure, patients may require more distal
      revascularization for limb salvage.

PMID- 11533608
TI  - Combined therapeutic approach of intra-arterial thrombolysis and carotid
      endarterectomy in selected patients with acute thrombotic carotid occlusion.
AB  - PURPOSE: The feasibility and clinical outcome of intra-arterial thrombolysis
      followed by carotid endarterectomy (CEA) for acute thrombotic occlusion of the
      internal carotid artery (ICA) were evaluated. METHODS: Intra-arterial
      thrombolysis and CEA were performed in four patients with acute thrombotic ICA
      occlusion. Computed tomography scans, cerebral angiograms, and the severity of
      carotid plaques were examined, and the patients' clinical outcome was evaluated.
      RESULTS: All 4 patients had severe hemiparesis; 3 patients were alert, and 1
      patient was lethargic at the time of hospital admission. New lesions were not
      shown by means of the initial computed tomography scan. ICA occlusion was
      indicated in all four patients by means of cerebral angiograms; in three
      patients, middle cerebral artery occlusion was noted. Collateral circulation was
      manifested in all patients. Partial recanalization of the occluded ICA was
      obtained in all patients. Two patients with severe residual ICA stenosis
      underwent an emergency CEA soon after thrombolysis; the other two patients were
      treated by means of CEA in the subacute or chromic stage. Plaque rupture and
      intraplaque hemorrhage were seen in all four patients. All four patients
      recovered completely, and restenosis of the ICA was not shown by means of follow
      up angiograms. CONCLUSION: Intra-arterial thrombolysis followed by CEA may be an
      effective therapeutic approach for treating acute thrombotic ICA occlusion. The
      optimal timing of CEA remains controversial.

PMID- 11533609
TI  - Dramatic remodeling of advanced atherosclerotic plaques of the apolipoprotein E
      deficient mouse in a novel transplantation model.
AB  - OBJECTIVE: Regression of atherosclerotic lesions is an important goal. No
      extensive experimental evidence shows that it can be achieved for advanced
      lesions. To study this, we developed a model to maintain a long-term change in
      the plasma lipoprotein environment of advanced arterial lesions of hyperlipidemic
      (apolipoprotein E [apoE]-deficient) mice. METHODS: The apoE-deficient mice
      (plasma total cholesterol of 1334 +/- 219 [+/- SEM] mg/dL) on a typical Western
      diet for 38 weeks had advanced atherosclerotic lesions (ie, beyond the macrophage
      foam cell stage) throughout the arterial tree. Lesion-containing thoracic aortas
      were transplanted (replacing a segment of abdominal aorta) into either apoE
      deficient or wild-type (WT) (total cholesterol of 86 +/- 10 mg/dL) recipients.
      Grafts were harvested after 9 weeks. RESULTS: Compared with pretransplant lesions
      (area = 0.0892 +/- 0.0179 mm(2)), lesion size tended to increase in apoE
      deficient to apoE-deficient grafts (0.2411 +/- 0.0636 mm(2); P =.06), whereas a
      significant reduction was seen in apoE-deficient to WT grafts (0.0214 +/- 0.0049
      mm(2); P <.001). Also, foam cells were absent in apoE-deficient to WT grafts, but
      abundant in pretransplant lesions and apoE-deficient to apoE-deficient grafts.
      Grafts were evaluated noninvasively in vivo with magnetic resonance imaging, and
      wall thickening was detected in the apoE-deficient to apoE-deficient group.
      CONCLUSIONS: Nearly complete regression of advanced atherosclerotic lesions can
      be achieved with sustained normalization of the plasma lipoprotein profile.
      Syngeneic arterial transplantation in mice is a novel and valuable model system
      for atherosclerosis research; and magnetic resonance imaging can detect
      differences in characteristics in lesions undergoing regression.

PMID- 11533610
TI  - Inhibition of neointima formation in an organ culture of human saphenous vein: a
      comparison of dual endothelin-converting enzyme/neutral endopeptidase and
      selective neutral endopeptidase inhibition.
AB  - PURPOSE: Endothelin-1 (ET-1) has been implicated in a variety of vascular
      pathologic conditions, although there is considerable controversy as to whether
      such effects are mediated by the ET-(A) or ET-(B) receptor. This study
      investigated whether inhibition of big ET-1 processing by inhibition of
      endothelin-converting enzyme (ECE) could, therefore, offer an alternative
      therapeutic strategy in the prevention of vein graft intimal hyperplasia.
      METHODS: Human saphenous vein (3 equal segments from 10 patients) were maintained
      in organ culture for 14 days with either 50 micromol/L CGS 26303 (a dual
      ECE/neutral endopeptidase [NEP] inhibitor), 50 micromol/L CGS 24592 (a selective
      NEP inhibitor), or vehicle (control). They were then processed for immunostaining
      and neointimal thickness measurements, and conditioned media was collected for
      enzyme-linked immunosorbent assay analysis. RESULTS: Neointimal thickness in the
      ECE/NEP-inhibited veins did not differ significantly from that of control
      segments. However, there was a highly significant augmentation in the NEP
      inhibited segments, consistent with an inhibition of ET-1 degradation (median
      difference, 16.8; 95% CI, -23.5, -10.4; P =.002, Wilcoxon). ECE immunostaining
      was reduced in the ECE/NEP-inhibited veins, although ET-1 staining was also
      present. ET-1 expression was intense in the thickened neointimas of NEP-inhibited
      veins, which also showed significant ECE staining. Elevated levels of big ET-1
      were measured in the ECE/NEP-inhibited veins, consistent with reduced ECE
      activity. However, mature ET-1 was still detectable in these segments.
      CONCLUSION: There is a requirement for potent and selective inhibitors of ECE to
      evaluate fully the potential therapeutic benefits of blocking ET-1 biosynthesis.
      The use of dual inhibitors complicates the interpretation of results, because the
      observed response is likely to be a combination of both ECE and NEP inhibition.

PMID- 11533611
TI  - PECAM-1/IgG attenuates peroxynitrite-mediated extremity reperfusion injury.
AB  - OBJECTIVE: Neutrophil transendothelial migration, a key feature of skeletal
      muscle ischemia and reperfusion (I/R) injury, is mediated by the platelet
      endothelial cell adhesion molecule-1 (PECAM-1). Peroxynitrite anion, a toxic
      product of neutrophil superoxide anion and nitric oxide, contributes to oxidative
      skeletal muscle injury and can be quantified by measurement of protein tyrosine
      nitration after I/R. This study hypothesizes that administration of the PECAM
      1/IgG antibody chimera will inhibit peroxynitrite-mediated injury after I/R.
      METHODS: The study was composed of five groups: an I/R group (n = 4), a sham
      treatment group anesthetic control (n = 3), a treatment group receiving the PECAM
      1/immunoglobulin G (IgG) antibody chimera with I/R (n = 9), a treatment group
      receiving human IgG with I/R as an antibody control (n = 6), and a treatment
      group receiving normal saline solution with I/R as a vehicle control (n = 5). The
      right hind limb in male New Zealand white rabbits was rendered ischemic by
      occluding the iliac and femoral arteries for 3 hours, followed by 2 hours of
      reperfusion (I/R). Sham-treated rabbits underwent arterial dissection without
      arterial occlusion. PECAM-1/IgG-treated rabbits and IgG-treated rabbits received
      an infusion of 1 mg/kg in normal saline solution 20 mL via an ear vein catheter
      during the last 5 minutes of ischemia and the first 15 minutes of reperfusion.
      Saline solution-treated rabbits similarly received normal saline solution 20 mL.
      The anterior tibialis muscle was harvested after reperfusion. Immunohistochemical
      staining for nitrotyrosine was performed with monoclonal antinitrotyrosine
      antibodies and fluorescently labeled secondary antibodies. Computed morphometric
      study was performed to calculate relative fluorescence scores for each histologic
      section. Averaged fluorescence scores were analyzed by one-way analysis of
      variance with Bonferroni post hoc comparison. RESULTS: The averaged fluorescence
      scores (mean +/- SEM) for the sham-treated (2.88 +/- 0.78) and PECAM-1/IgG
      treated (6.16 +/- 0.43) groups demonstrated a significant reduction in
      quantitative fluorescence compared with the IgG- (15.17 +/- 2.01) and saline
      solution-treated (17.46 +/- 3.71) control groups, and the I/R-treated (18.52 +/-
      3.00) group, (P <.05). CONCLUSIONS: These results suggest that PECAM-1/IgG
      diminishes peroxynitrite-mediated oxidative skeletal muscle injury by inhibiting
      neutrophil transendothelial migration and may therefore prove a useful
      therapeutic agent in the treatment of reperfusion injury.

PMID- 11533612
TI  - Abdominal compartment syndrome after mesenteric revascularization.
AB  - Abdominal compartment syndrome (ACS) results from increased pressure within the
      abdominal cavity leading to multisystem organ dysfunction. The most common cause
      of ACS is increased intraperitoneal volume from any source, but extrinsic
      compression can also cause increased intra-abdominal pressure. Although ACS has
      been well described in patients with trauma, little has been reported on ACS in
      postoperative patients without traumatic injuries. We report on a patient who had
      acute ACS 2 days after surgical revascularization for chronic mesenteric
      ischemia. With appropriate treatment, the patient made a rapid and complete
      recovery. We present this case of acute ACS in the postoperative patient without
      trauma to increase awareness and help minimize death caused by this devastating
      syndrome.

PMID- 11533613
TI  - Traumatic renal artery dissection identified with dynamic helical computed
      tomography.
AB  - Intimal tears in the renal arteries typically result from traumatic mechanisms
      that produce rapid deceleration. These injuries usually progress to secondary
      thrombosis of the vessel. When the tear leads to dissection with luminal
      stenosis, early diagnosis and repair will preserve parenchymal function. Computed
      tomography has replaced intravenous pyelography as the radiographic study of
      choice for renal trauma. We present two patients with unilateral delay of renal
      contrast enhancement during dynamic helical computed tomography scan due to
      arterial stenosis from intimal dissection confirmed with arteriography. Both
      vessel injuries were successfully managed with endovascular stent placement. No
      previous description of this diagnostic strategy is reported in the literature.

PMID- 11533614
TI  - A new vascular Endostaple: a technical description.
AB  - OBJECTIVE: The purpose of this report is to describe a new vascular Endostapling
      system. METHODS: The vascular Endostapling system can be passed through a 13F
      insertion sheath that is inserted through the femoral artery. An optical fiber
      and overlying Endostaple will penetrate a previously inserted endoprosthesis and
      the aortic wall at whatever points are desired. Once the optical fiber is
      withdrawn, the Endostaple assumes its preformed shape and acts like a through-and
      through wire suture. As tissue ingrowth proceeds, the long-term security and
      stabilization of the coiled coil mechanism are likely to increase. CONCLUSIONS:
      We think Endostaples can be useful in preventing endograft migration and in
      treating endoleak at the site of the aortic neck-proximal endograft interface.

PMID- 11533615
TI  - Carotid endarterectomy: a champion turns fifty.

PMID- 11533617
TI  - Regarding "Surgical treatment of venous malformations in Klippel-Trenaunay
      syndrome".

PMID- 11533618
TI  - The politics of principles.

PMID- 11533619
TI  - US deliberates on embryonic stem cells, cloning.

PMID- 11533620
TI  - New Zealand backs GM technologies.

PMID- 11533621
TI  - US rejects stronger bioweapons treaty.

PMID- 11533622
TI  - IT giants muscle into life science arena.

PMID- 11533623
TI  - EU plans to label and trace GMOs.

PMID- 11533624
TI  - Racially defined haplotype project debated.

PMID- 11533625
TI  - GM crops are no panacea for poverty.

PMID- 11533626
TI  - Quicker drug approvals on the way for Europe.

PMID- 11533628
TI  - The protein trinity--linking function and disorder.

PMID- 11533629
TI  - The Bush administration deals a blow to biotechnology--and itself.

PMID- 11533631
TI  - Too much of a good thing?

PMID- 11533632
TI  - In defense of the precautionary principle.

PMID- 11533633
TI  - Estrogenic impurities in labware.

PMID- 11533634
TI  - Putting a price on biotechnology.

PMID- 11533635
TI  - Monoclonal antibodies in the clinic.

PMID- 11533636
TI  - Listening for viral infection.

PMID- 11533637
TI  - Genetic selection and the lure of SIN.

PMID- 11533638
TI  - Plastid engineering bears fruit.

PMID- 11533639
TI  - Proteomics comes to the surface.

PMID- 11533641
TI  - Direct and sensitive detection of a human virus by rupture event scanning.
AB  - We have developed a sensitive, economical method that directly detects viruses by
      making use of the interaction between type 1 herpes simplex virus (HSV1) and
      specific antibodies covalently attached to the oscillating surface of a quartz
      crystal microbalance (QCM). The virions were detached from the surface by
      monotonously increasing the amplitude of oscillation of the QCM, while using the
      QCM to sensitively detect the acoustic noise produced when the interactions were
      broken. We term this process rupture event scanning (REVS). The method is
      quantitative over at least six orders of magnitude, and its sensitivity
      approaches detection of a single virus particle.

PMID- 11533642
TI  - Combined transductional and transcriptional targeting improves the specificity of
      transgene expression in vivo.
AB  - The promise of gene therapy for health care will not be realized until gene
      delivery systems are capable of achieving efficient, cell-specific gene delivery
      in vivo. Here we describe an adenoviral system for achieving cell-specific
      transgene expression in pulmonary endothelium. The combination of transductional
      targeting to a pulmonary endothelial marker (angiotensin-converting enzyme, ACE)
      and an endothelial-specific promoter (for vascular endothelial growth factor
      receptor type 1, flt-1) resulted in a synergistic, 300,000-fold improvement in
      the selectivity of transgene expression for lung versus the usual site of vector
      sequestration, the liver. This combined approach should be useful for the design
      of other gene delivery systems.

PMID- 11533643
TI  - High-yield selection and extraction of two promoter-defined phenotypes of neural
      stem cells from the fetal human brain.
AB  - Neural stem and precursor cells reside in the ventricular lining of the fetal
      forebrain, and may provide a cellular substrate for brain repair. To selectively
      identify and extract these cells, we infected dissociated fetal human brain cells
      with adenoviruses bearing the gene for green fluorescence protein (GFP), placed
      under the control of enhancer/promoters for two genes (nestin and musashi1) that
      are expressed in uncommitted neuroepithelial cells. The cells were then sorted by
      fluorescence-activated cell sorting (FACS) on the basis of E/nestin- or
      P/musashi1-driven GFP expression. Both P/musashi1:hGFP- and E/nestin:EGFP-sorted
      cells were multipotent: limiting dilution with clonal expansion as neurospheres,
      in tandem with retroviral lineage analysis and xenograft to E17 and P0-2 rat
      forebrain, revealed that each phenotype was able to both self-renew and co
      generate neurons and glia. Thus, fluorescent genes placed under the control of
      early neural promoters allow neural stem cells to be specifically targeted,
      isolated, and substantially enriched from the fetal human brain.

PMID- 11533644
TI  - A high-throughput alphavirus-based expression cloning system for mammalian cells.
AB  - We have developed a widely applicable functional genomics strategy based on
      alphavirus expression vectors. The technology allows for rapid identification of
      genes encoding a functional activity such as binding of a defined ligand.
      Complementary DNA (cDNA) libraries were expressed in mammalian cells following
      infection with recombinant Sindbis virus (SIN replicon particles), a member of
      the Alphavirus genus. Virus-infected cells that specifically bound a ligand of
      choice were isolated using fluorescence-activated cell sorting (FACS).
      Replication-competent, infective SIN replicon particles harboring the
      corresponding cDNA were amplified in a next step. Within one round of selection,
      viral clones encoding proteins recognized by monoclonal antibodies or Fc-fusion
      molecules could be isolated and sequenced. Moreover, using the same viral
      libraries, a plaque-lift assay was established that allowed the identification of
      secreted, intracellular, and membrane proteins.

PMID- 11533645
TI  - Bioassay of prostate-specific antigen (PSA) using microcantilevers.
AB  - Diagnosis and monitoring of complex diseases such as cancer require quantitative
      detection of multiple proteins. Recent work has shown that when specific
      biomolecular binding occurs on one surface of a microcantilever beam,
      intermolecular nanomechanics bend the cantilever, which can be optically
      detected. Although this label-free technique readily lends itself to formation of
      microcantilever arrays, what has remained unclear is the technologically critical
      issue of whether it is sufficiently specific and sensitive to detect disease
      related proteins at clinically relevant conditions and concentrations. As an
      example, we report here that microcantilevers of different geometries have been
      used to detect two forms of prostate-specific antigen (PSA) over a wide range of
      concentrations from 0.2 ng/ml to 60 microg/ml in a background of human serum
      albumin (HSA) and human plasminogen (HP) at 1 mg/ml, making this a clinically
      relevant diagnostic technique for prostate cancer. Because cantilever motion
      originates from the free-energy change induced by specific biomolecular binding,
      this technique may offer a common platform for high-throughput label-free
      analysis of protein-protein binding, DNA hybridization, and DNA-protein
      interactions, as well as drug discovery.

PMID- 11533646
TI  - Single-molecule observation of protein-protein interactions in the chaperonin
      system.
AB  - We have analyzed the dynamics of the chaperonin (GroEL)-cochaperonin (GroES)
      interaction at the single-molecule level. In the presence of ATP and non-native
      protein, binding of GroES to the immobilized GroEL occurred at a rate that is
      consistent with bulk kinetics measurements. However, the release of GroES from
      GroEL occurred after a lag period ( approximately 3 s) that was not recognized in
      earlier bulk-phase studies. This observation suggests a new kinetic intermediate
      in the GroEL-GroES reaction pathway.

PMID- 11533647
TI  - Affinity capture of proteins from solution and their dissociation by contact
      printing.
AB  - Biological experiments at the solid/liquid interface, in general, require
      surfaces with a thin layer of purified molecules, which often represent precious
      material. Here, we have devised a method to extract proteins with high
      selectivity from crude biological sample solutions and place them on a surface in
      a functional, arbitrary pattern. This method, called affinity-contact printing
      (alphaCP), uses a structured elastomer derivatized with ligands against the
      target molecules. After the target molecules have been captured, they are printed
      from the elastomer onto a variety of surfaces. The ligand remains on the stamp
      for reuse. In contrast with conventional affinity chromatography, here
      dissociation and release of captured molecules to the substrate are achieved
      mechanically. We demonstrate this technique by extracting the cell adhesion
      molecule neuron-glia cell adhesion molecule (NgCAM) from tissue homogenates and
      cell culture lysates and patterning affinity-purified NgCAM on polystyrene to
      stimulate the attachment of neuronal cells and guide axon outgrowth.

PMID- 11533648
TI  - Stable genetic transformation of tomato plastids and expression of a foreign
      protein in fruit.
AB  - Transgenic chloroplasts offer unique advantages in plant biotechnology, including
      high-level foreign protein expression, absence of epigenetic effects, and gene
      containment due to the lack of transgene transmission through pollen. However,
      broad application of plastid genome engineering in biotechnology has been largely
      hampered by both the lack of chloroplast transformation systems for major crop
      plants and the usually low plastid gene expression levels in nongreen tissues
      such as fruits, tubers, and other storage organs. Here we describe the
      development of a plastid transformation system for tomato, Lycopersicon
      esculentum. This is the first report on the generation of fertile transplastomic
      plants in a food crop with an edible fruit. We show that chromoplasts in the
      tomato fruit express the transgene to approximately 50% of the expression levels
      in leaf chloroplasts. Given the generally very high foreign protein accumulation
      rates that can be achieved in transgenic chloroplasts (>40% of the total soluble
      protein), this system paves the way to efficient production of edible vaccines,
      pharmaceuticals, and antibodies in tomato.

PMID- 11533649
TI  - Genotyping of dinucleotide tandem repeats by MALDI mass spectrometry of ribozyme
      cleaved RNA transcripts.
AB  - We describe a method for high-throughput typing of short tandem repeat (STR)
      polymorphisms. Current gel electrophoresis techniques allow only moderate
      throughput with long hands-on and analysis time, and the output is on a relative
      scale of electrophoretic mobility, prone to artifacts. Matrix-assisted laser-
      desorption/ionization mass spectrometry (MALDI-MS) enables an automated high
      throughput and delivers accurate data directly depicting the molecular nature of
      the analyte. Analysis of large DNA fragments, however, is limited by adduct
      formation and fragmentation, which result in peak broadening and low signal
      intensity. MALDI typing of polymorphic STRs has been reported for tri- and
      tetranucleotide repeats with sufficient resolution to distinguish alleles. For
      dinucleotide repeats, essential in animal genome studies, an enhanced resolution
      is necessary. Increased mass resolution was reported for RNA (ref. 7) and
      modified DNA (refs 8-10) due to substituents that disfavor intramolecular
      reactions leading to fragmentation. RNA transcripts can be synthesized
      enzymatically from PCR products containing a promoter sequence, requiring no
      specialty reagents or primer labels. Furthermore, RNA transcripts are single
      stranded, a prerequisite for high-resolution mass spectrometry of nucleic acids.
      The 3' heterogeneities produced by viral RNA polymerases, however, impede exact
      sizing of RNA runoff transcripts. Non-templated multiple-base extensions as well
      as premature termination have been reported. PCR of dinucleotide repeats tends
      toward the deletion of repeat units, generating a complex pattern of interleaved
      extensions (from RNA polymerase) and deletions (from PCR) that obscure the true
      allele size. We overcome this obstacle by adding a 3' sequence encoding a
      catalytic RNA sequence, the so-called hammerhead ribozyme, that cleaves itself co
      transcriptionally, creating a homogeneous 3' end.

PMID- 11533650
TI  - Going for the big one.

PMID- 11533654
TI  - Finance offers intellectual challenges and economic rewards.

PMID- 11533655
TI  - Orchestrating anaphase and mitotic exit: separase cleavage and localization of
      Slk19.
AB  - Anaphase in budding yeast is triggered by cleavage of the central subunit, Scc1,
      of the chromosomal cohesin complex by the protease separase. Here we show that
      separase also cleaves the kinetochore-associated protein Slk19 at anaphase onset.
      Separase activity is also required for the proper localization of a stable Slk19
      cleavage product to the spindle midzone in anaphase. The cleavage and
      localization of Slk19 are necessary to stabilize the anaphase spindle, and we
      show that a stable spindle is a prerequisite for timely exit from mitosis. This
      demonstrates the cleavage of targets other than cohesin by separase in the
      orchestration of high-fidelity anaphase.

PMID- 11533656
TI  - Isolation of multipotent adult stem cells from the dermis of mammalian skin.
AB  - We describe here the isolation of stem cells from juvenile and adult rodent skin.
      These cells derive from the dermis, and clones of individual cells can
      proliferate and differentiate in culture to produce neurons, glia, smooth muscle
      cells and adipocytes. Similar precursors that produce neuron-specific proteins
      upon differentiation can be isolated from adult human scalp. Because these cells
      (termed SKPs for skin-derived precursors) generate both neural and mesodermal
      progeny, we propose that they represent a novel multipotent adult stem cell and
      suggest that skin may provide an accessible, autologous source of stem cells for
      transplantation.

PMID- 11533657
TI  - ErbB2, but not ErbB1, reinitiates proliferation and induces luminal repopulation
      in epithelial acini.
AB  - Both ErbB1 and ErbB2 are overexpressed or amplified in breast tumours. To examine
      the effects of activating ErbB receptors in a context that mimics polarized
      epithelial cells in vivo, we activated ErbB1 and ErbB2 homodimers in preformed,
      growth-arrested mammary acini cultured in three-dimensional basement membrane
      gels. Activation of ErbB2, but not that of ErbB1, led to a reinitiation of cell
      proliferation and altered the properties of mammary acinar structures. These
      altered structures share several properties with early-stage tumours, including a
      loss of proliferative suppression, an absence of lumen, retention of the basement
      membrane and a lack of invasive properties. ErbB2 activation also disrupted tight
      junctions and the cell polarity of polarized epithelia, whereas ErbB1 activation
      did not have any effect. Our results indicate that ErbB receptors differ in their
      ability to induce early stages of mammary carcinogenesis in vitro and this three
      dimensional model system can reveal biological activities of oncogenes that
      cannot be examined in vitro in standard transformation assays.

PMID- 11533658
TI  - Pin1 regulates turnover and subcellular localization of beta-catenin by
      inhibiting its interaction with APC.
AB  - Phosphorylation on a serine or threonine residue preceding proline (Ser/Thr-Pro)
      is a key regulatory mechanism, and the conformation of certain phosphorylated
      Ser/Thr-Pro bonds is regulated specifically by the prolyl isomerase Pin1. Whereas
      the inhibition of Pin1 induces apoptosis, Pin1 is strikingly overexpressed in a
      subset of human tumours. Here we show that Pin1 regulates beta-catenin turnover
      and subcellular localization by interfering with its interaction with adenomatous
      polyposis coli protein (APC). A differential-display screen reveals that Pin1
      increases the transcription of several beta-catenin target genes, including those
      encoding cyclin D1 and c-Myc. Manipulation of Pin1 levels affects the stability
      of beta-catenin in vitro. Furthermore, beta-catenin levels are decreased in Pin1
      deficient mice but are increased and correlated with Pin1 overexpression in human
      breast cancer. Pin1 directly binds a phosphorylated Ser-Pro motif next to the APC
      binding site in beta-catenin, inhibits its interaction with APC and increases its
      translocation into the nucleus. Thus, Pin1 is a novel regulator of beta-catenin
      signalling and its overexpression might contribute to the upregulation of beta
      catenin in tumours such as breast cancer, in which APC or beta-catenin mutations
      are not common.

PMID- 11533659
TI  - Nuclear localization of EGF receptor and its potential new role as a
      transcription factor.
AB  - Epidermal growth factor receptor (EGFR) has been detected in the nucleus in many
      tissues and cell lines. However, the potential functions of nuclear EGFR have
      largely been overlooked. Here we demonstrate that nuclear EGFR is strongly
      correlated with highly proliferating activities of tissues. When EGFR was fused
      to the GAL4 DNA-binding domain, we found that the carboxy terminus of EGFR
      contained a strong transactivation domain. Moreover, the receptor complex bound
      and activated AT-rich consensus-sequence-dependent transcription, including the
      consensus site in cyclin D1 promoter. By using chromatin immunoprecipitation
      assays, we further demonstrated that nuclear EGFR associated with promoter region
      of cyclin D1 in vivo. EGFR might therefore function as a transcription factor to
      activate genes required for highly proliferating activities.

PMID- 11533660
TI  - Dual role of the fringe connection gene in both heparan sulphate and fringe
      dependent signalling events.
AB  - The precise regulation of growth factor signalling is crucial to the molecular
      control of development in Drosophila. Post-translational modification of
      signalling molecules is one of the mechanisms that modulate developmental
      signalling specificity. We describe a new gene, fringe connection (frc), that
      encodes a nucleotide-sugar transporter that transfers UDP-glucuronic acid, UDP-N
      acetylglucosamine and possibly UDP-xylose from the cytoplasm into the lumen of
      the endoplasmic reticulum/Golgi. Embryos with the frc mutation display defects in
      Wingless, Hedgehog and fibroblast growth factor signalling. Clonal analysis shows
      that fringe-dependent Notch signalling is disrupted in frc mutant tissue.

PMID- 11533661
TI  - UDP-sugar transporter implicated in glycosylation and processing of Notch.
AB  - Glycosylation modifies protein activities in various biological processes. Here,
      we report the functions of a novel UDP-sugar transporter (UST74C, an alternative
      name for Fringe connection (Frc)) localized to the Golgi apparatus in cellular
      signalling of Drosophila. Mutants in the frc gene exhibit phenotypes resembling
      wingless and Notch mutants. Both Fringe-dependent and Fringe-independent Notch
      pathways are affected, and both glycosylation and proteolytic maturation of Notch
      are defective in mutant larvae. The results suggest that changes in nucleotide
      sugar levels can differently affect Wingless and two distinct aspects of Notch
      signalling.

PMID- 11533662
TI  - Desmosomal adhesion regulates epithelial morphogenesis and cell positioning.
AB  - Desmosomes are intercellular junctions of epithelia and are of widespread
      importance in the maintenance of tissue architecture. We provide evidence that
      desmosomal adhesion has a function in epithelial morphogenesis and cell-type
      specific positioning. Blocking peptides corresponding to the cell adhesion
      recognition (CAR) sites of desmosomal cadherins block alveolar morphogenesis by
      epithelial cells from mammary lumen. Desmosomal CAR-site peptides also disrupt
      positional sorting of luminal and myoepithelial cells in aggregates formed by the
      reassociation of isolated cells. We demonstrate that desmosomal cadherins and E
      cadherin are comparably involved in epithelial morphoregulation. The results
      indicate a wider role for desmosomal adhesion in morphogenesis than has
      previously been considered.

PMID- 11533663
TI  - Rac1 orientates epithelial apical polarity through effects on basolateral laminin
      assembly.
AB  - Cellular polarization involves the generation of asymmetry along an intracellular
      axis. In a multicellular tissue, the asymmetry of individual cells must conform
      to the overlying architecture of the tissue. However, the mechanisms that couple
      cellular polarization to tissue morphogenesis are poorly understood. Here, we
      report that orientation of apical polarity in developing Madin-Darby canine
      kidney (MDCK) epithelial cysts requires the small GTPase Rac1 and the basement
      membrane component laminin. Dominant-negative Rac1 alters the supramolecular
      assembly of endogenous MDCK laminin and causes a striking inversion of apical
      polarity. Exogenous laminin is recruited to the surface of these cysts and
      rescues apical polarity. These findings implicate Rac1-mediated laminin assembly
      in apical pole orientation. By linking apical orientation to generation of the
      basement membrane, epithelial cells ensure the coordination of polarity with
      tissue architecture.

PMID- 11533664
TI  - Heat-shock protein 70 antagonizes apoptosis-inducing factor.
AB  - Heat-shock protein 70 (Hsp70) has been reported to block apoptosis by binding
      apoptosis protease activating factor-1 (Apaf-1), thereby preventing constitution
      of the apoptosome, the Apaf-1/cytochrome c/caspase-9 activation complex [1,2].
      Here we show that overexpression of Hsp70 protects Apaf-1-/- cells against death
      induced by serum withdrawal, indicating that Apaf-1 is not the only target of the
      anti-apoptotic action of Hsp70. We investigated the effect of Hsp70 on apoptosis
      mediated by the caspase-independent death effector apoptosis inducing factor
      (AIF), which is a mitochondrial intermembrane flavoprotein [3,4]. In a cell-free
      system, Hsp70 prevented the AIF-induced chromatin condensation of purified
      nuclei. Hsp70 specifically interacted with AIF, as shown by ligand blots and co
      immunoprecipitation. Cells overexpressing Hsp70 were protected against the
      apoptogenic effects of AIF targeted to the extramitochondrial compartment. In
      contrast, an anti-sense Hsp70 complementary DNA, which reduced the expression of
      endogenous Hsp70, increased sensitivity to the lethal effect of AIF. The ATP
      binding domain of Hsp70 seemed to be dispensable for inhibiting cell death
      induced by serum withdrawal, AIF binding and AIF inhibition, although it was
      required for Apaf-1 binding. Together, our data indicate that Hsp70 can inhibit
      apoptosis by interfering with target proteins other than Apaf-1, one of which is
      AIF.

PMID- 11533665
TI  - Checkpoint activation in response to double-strand breaks requires the
      Mre11/Rad50/Xrs2 complex.
AB  - Studies of human Nijmegen breakage syndrome (NBS) cells have led to the proposal
      that the Mre11/Rad50/ NBS1 complex, which is involved in the repair of DNA double
      strand breaks (DSBs), might also function in activating the DNA damage checkpoint
      pathways after DSBs occur. We have studied the role of the homologous budding
      yeast complex, Mre11/Rad50/Xrs2, in checkpoint activation in response to DSB
      inducing agents. Here we show that this complex is required for phosphorylation
      and activation of the Rad53 and Chk1 checkpoint kinases specifically in response
      to DSBs. Consistent with defective Rad53 activation, we observed defective cell
      cycle delays after induction of DSBs in the absence of Mre11. Furthermore, after
      gamma-irradiation phosphorylation of Rad9, which is an early event in checkpoint
      activation, is also dependent on Mre11. All three components of the
      Mre11/Rad50/Xrs2 complex are required for activation of Rad53, however, the Ku80,
      Rad51 or Rad52 proteins, which are also involved in DSB repair, are not. Thus,
      the integrity of the Mre11/Rad50/Xrs2 complex is specifically required for
      checkpoint activation after the formation of DSBs.

PMID- 11533666
TI  - A nuclear lamin is required for cytoplasmic organization and egg polarity in
      Drosophila.
AB  - Nuclear lamins are intermediate filaments that compose the nuclear lamina--the
      filamentous meshwork underlying the inner nuclear membrane--and are required for
      nuclear assembly, organization and maintenance. Here we present evidence that a
      nuclear lamin is also required for cytoplasmic organization in two highly
      polarized cell types. Zygotic loss-of-function mutations in the Drosophila gene
      encoding the principal lamin (Dm(0)) disrupt the directed outgrowth of
      cytoplasmic extensions from terminal cells of the tracheal system. Germline
      mutant clones disrupt dorsal-ventral polarity of the oocyte. In mutant oocytes,
      transcripts of the dorsal determinant Gurken, a transforming growth factor-alpha
      homologue, fail to localize properly around the anterodorsal surface of the
      oocyte nucleus; their ventral spread results in dorsalized eggs that resemble
      those of the classical dorsalizing mutations squid and fs(1)K10. The requirement
      of a nuclear lamin for cytoplasmic as well as nuclear organization has important
      implications for both the cellular functions of lamins and the pathogenesis of
      human diseases caused by lamin mutations.

PMID- 11533667
TI  - Four-dimensional imaging and quantitative reconstruction to analyse complex
      spatiotemporal processes in live cells.
AB  - Live-cell imaging technology using fluorescent proteins (green fluorescent
      protein and its homologues) has revolutionized the study of cellular dynamics.
      But tools that can quantitatively analyse complex spatiotemporal processes in
      live cells remain lacking. Here we describe a new technique--fast multi-colour
      four-dimensional imaging combined with automated and quantitative time-space
      reconstruction--to fill this gap. As a proof of principle, we apply this method
      to study the re-formation of the nuclear envelope in live cells. Four-dimensional
      imaging of three spectrally distinct fluorescent proteins is used to
      simultaneously visualize three different cellular compartments at high speed and
      with high spatial resolution. The highly complex data, comprising several
      thousand images from a single cell, were quantitatively reconstructed in time
      space by software developed in-house. This analysis reveals quantitative and
      qualitative insights into the highly ordered topology of nuclear envelope
      formation, in correlation with chromatin expansion - results that would have been
      impossible to achieve by manual inspection alone. Our new technique will greatly
      facilitate study of the highly ordered dynamic architecture of eukaryotic cells.

PMID- 11533668
TI  - Enteropathogenic E. coli Tir binds Nck to initiate actin pedestal formation in
      host cells.
AB  - Enteropathogenic Escherichia coli (EPEC) is a bacterial pathogen that causes
      infantile diarrhea worldwide. EPEC injects a bacterial protein, translocated
      intimin receptor (Tir), into the host-cell plasma membrane where it acts as a
      receptor for the bacterial outer membrane protein, intimin. The interaction of
      Tir and intimin triggers a marked rearrangement of the host actin cytoskeleton
      into pedestals beneath adherent bacteria. On delivery into host cells, EPEC Tir
      is phosphorylated on tyrosine 474 of the intracellular carboxy-terminal domain,
      an event that is required for pedestal formation. Despite its essential role, the
      function of Tir tyrosine phosphorylation has not yet been elucidated. Here we
      show that tyrosine 474 of Tir directly binds the host-cell adaptor protein Nck,
      and that Nck is required for the recruitment of both neural Wiskott-Aldrich
      syndrome protein (N-WASP) and the actin-related protein (Arp)2/3 complex to the
      EPEC pedestal, directly linking Tir to the cytoskeleton. Cells with null alleles
      of both mammalian Nck genes are resistant to the effects of EPEC on the actin
      cytoskeleton. These results implicate Nck adaptors as host-cell determinants of
      EPEC virulence.

PMID- 11533669
TI  - The price of a PhD.

PMID- 11533670
TI  - A new view of mRNA export: separating the wheat from the chaff.
AB  - Current models for the export of messenger RNA share the notion that the highly
      abundant class of nuclear RNA-binding proteins--the hnRNP proteins--have a key
      role in exporting RNA. But recent studies have led to a new understanding of
      several non-hnRNP proteins, including SR proteins and the conserved mRNA export
      factor ALY, which are recruited to the mRNA during pre-mRNA splicing. These
      studies, together with older work on hnRNP particles and assembly of the
      spliceosome, lead us to a new view of mRNA export. In our model, the non-hnRNP
      factors form a splicing-dependent mRNP complex that specifically targets mature
      mRNA for export, while hnRNP proteins retain introns in the nucleus. A machinery
      that is conserved between yeast and higher eukaryotes functions to export the
      mRNA.

PMID- 11533671
TI  - Skinny dipping for stem cells.
AB  - Stem cells have been big news for the past couple of years and yet they remain
      remarkably inscrutable in terms of declaring their true nature and identity. On
      pages 778-784 of this issue, Toma et al. describe the identification of a new
      type of stem cell from the dermis of ths skin, called skin-derived precursor
      (SKP) cells. These can be converted into several differentiated cell types in
      vitro, including neurons, and might become a source of cells for therapeutic
      tissue repair.

PMID- 11533673
TI  - Separase anxiety: dissolving the sister bond and more.
AB  - Separase is a protease that cleaves the bonds between sister chromatids during
      cell division. Until now, separase was thought to be a somewhat repressed
      protease, cleaving only a few substrates in a very controlled fashion. New
      findings in this issue raise the possibility that separase has some of the
      atavistic impulses that characterize caspases, its more destructive relatives.

PMID- 11533675
TI  - EGF receptors as transcription factors: ridiculous or sublime?
AB  - The notion that a transmembrane receptor at the cell surface can somehow reappear
      as a transcription factor in the nucleus is bound to be controversial. However,
      there are two reported examples of this. If this hypothesis can withstand the
      inevitable and necessary battery of additional empirical tests, then our
      understanding of signal transduction needs to move in a new direction.

PMID- 11533679
TI  - Tracing the lineage of tracing cell lineages.
AB  - The study of cell lineages has been, and remains, of crucial importance in
      developmental biology. It requires the identification of a cell or group of cells
      and of all of their descendants during embryonic development. Here, we provide a
      brief survey of how different techniques for achieving this have evolved over the
      last 100 years.

PMID- 11533680
TI  - More good than harm.

PMID- 11533681
TI  - Transepithelial prion transport by M cells.

PMID- 11533682
TI  - Inhibition of post-ischemic brain injury by clusterin overexpression.

PMID- 11533684
TI  - Bush policy: attention turns to existing human ES cells.

PMID- 11533687
TI  - Canadian doctors unhappy at prescribing 'medicine'.

PMID- 11533689
TI  - Proteomics: basic research climbs aboard.

PMID- 11533692
TI  - Normalizing tumor vasculature with anti-angiogenic therapy: a new paradigm for
      combination therapy.

PMID- 11533695
TI  - Will the drugs still work? Transmission of resistant HIV.

PMID- 11533696
TI  - Excitotoxic destruction facilitates brain tumor growth.

PMID- 11533698
TI  - Nimble progenitors rescue vascular grafts.

PMID- 11533699
TI  - Neural stem cells--where are you?

PMID- 11533700
TI  - Receptor double-trouble in preeclampsia.

PMID- 11533702
TI  - Increased AT(1) receptor heterodimers in preeclampsia mediate enhanced
      angiotensin II responsiveness.
AB  - Several examples of functional G-protein-coupled receptor heterodimers have been
      identified. However, it is not known whether receptor heterodimerization is
      involved in the pathogenesis of human disorders. Here we show that in
      preeclamptic hypertensive women, a significant increase in heterodimerization
      occurs between the AT(1)-receptor for the vasopressor angiotensin II and the B(2)
      receptor for the vasodepressor bradykinin. AT(1)-B(2)-receptor heterodimerization
      in preeclampsia correlated with a 4-5-fold increase in B(2)-receptor protein
      levels. Expression of the AT(1)-B(2) heterodimer increased the responsiveness to
      angiotensin II and conferred resistance in AT(1)-receptors to inactivation by
      reactive oxygen species raised in normotensive and preeclamptic pregnancies. We
      suggest that AT(1)-B(2) heterodimers contribute to angiotensin II
      hypersensitivity in preeclampsia. Moreover, we identify preeclampsia as the first
      disorder associated with altered G-protein-coupled receptor heterodimerization.

PMID- 11533703
TI  - Glutamate release promotes growth of malignant gliomas.
AB  - Glutamate neurotoxicity has been implicated in stroke, head trauma, multiple
      sclerosis and neurodegenerative diseases. Although recent data show that cultured
      glioma cells secrete glutamate, the growth potential of brain tumors has not yet
      been linked to an excitotoxic mechanism. Using bioluminescence detection of
      glutamate release from freshly prepared brain slices, we show that implanted
      glioma cells continue to secrete glutamate. Moreover, gliomas with high glutamate
      release have a distinct growth advantage in host brain that is not present in
      vitro. Treatment with the NMDA receptor antagonists MK801 or memantine slowed the
      growth of glutamate-secreting tumors in situ, suggesting that activation of NMDA
      receptors facilitates tumor expansion. These findings support a new approach for
      therapy of brain tumors, based upon antagonizing glutamate secretion or its
      target receptors.

PMID- 11533704
TI  - Predicting the unpredictable: transmission of drug-resistant HIV.
AB  - We use a mathematical model to understand (from 1996 to 2001) and to predict
      (from 2001 to 2005) the evolution of the epidemic of drug-resistant HIV in San
      Francisco. We predict the evolutionary trajectories for 1,000 different drug
      resistant strains with each strain having a different fitness relative to a drug
      sensitive strain. We calculate that the current prevalence of resistance is high,
      and predict it will continue to rise. In contrast, we calculate that transmission
      of resistance is currently low, and predict it will remain low. We show that the
      epidemic of resistance is being generated mainly by the conversion of drug
      sensitive cases to drug-resistant cases, and not by the transmission of resistant
      strains. We also show that transmission of resistant strains has not increased
      the overall number of new HIV infections. Our results indicate that transmission
      of resistant strains is, and will remain, a relatively minor public health
      problem.

PMID- 11533705
TI  - Abrupt rate accelerations or premature beats cause life-threatening arrhythmias
      in mice with long-QT3 syndrome.
AB  - Deletion of amino-acid residues 1505-1507 (KPQ) in the cardiac SCN5A Na(+)
      channel causes autosomal dominant prolongation of the electrocardiographic QT
      interval (long-QT syndrome type 3 or LQT3). Excessive prolongation of the action
      potential at low heart rates predisposes individuals with LQT3 to fatal
      arrhythmias, typically at rest or during sleep. Here we report that mice
      heterozygous for a knock-in KPQ-deletion (SCN5A(Delta/+)) show the essential LQT3
      features and spontaneously develop life-threatening polymorphous ventricular
      arrhythmias. Unexpectedly, sudden accelerations in heart rate or premature beats
      caused lengthening of the action potential with early afterdepolarization and
      triggered arrhythmias in Scn5a(Delta/+) mice. Adrenergic agonists normalized the
      response to rate acceleration in vitro and suppressed arrhythmias upon premature
      stimulation in vivo. These results show the possible risk of sudden heart-rate
      accelerations. The Scn5a(Delta/+) mouse with its predisposition for pacing
      induced arrhythmia might be useful for the development of new treatments for the
      LQT3 syndrome.

PMID- 11533706
TI  - The ABC transporter Bcrp1/ABCG2 is expressed in a wide variety of stem cells and
      is a molecular determinant of the side-population phenotype.
AB  - Stem cells from bone marrow, skeletal muscle and possibly other tissues can be
      identified by the 'side-population' (SP) phenotype. Although it has been assumed
      that expression of ABC transporters is responsible for this phenotype, the
      specific molecules involved have not been defined. Here we show that expression
      of the Bcrp1 (also known as Abcg2 murine/ABCG2 human) gene is a conserved feature
      of stem cells from a wide variety of sources. Bcrp1 mRNA was expressed at high
      levels in primitive murine hematopoietic stem cells, and was sharply
      downregulated with differentiation. Enforced expression of the ABCG2 cDNA
      directly conferred the SP phenotype to bone-marrow cells and caused a reduction
      in maturing progeny both in vitro and in transplantation-based assays. These
      results show that expression of the Bcrp1/ABCG2 gene is an important determinant
      of the SP phenotype, and that it might serve as a marker for stem cells from
      various sources.

PMID- 11533707
TI  - Functional small-diameter neovessels created using endothelial progenitor cells
      expanded ex vivo.
AB  - Arterial conduits are increasingly preferred for surgical bypass because of
      inherent functional properties conferred by arterial endothelial cells,
      especially nitric oxide production in response to physiologic stimuli. Here we
      tested whether endothelial progenitor cells (EPCs) can replace arterial
      endothelial cells and promote patency in tissue-engineered small-diameter blood
      vessels (4 mm). We isolated EPCs from peripheral blood of sheep, expanded them ex
      vivo and then seeded them on decellularized porcine iliac vessels. EPC-seeded
      grafts remained patent for 130 days as a carotid interposition graft in sheep,
      whereas non-seeded grafts occluded within 15 days. The EPC-explanted grafts
      exhibited contractile activity and nitric-oxide-mediated vascular relaxation that
      were similar to native carotid arteries. These results indicate that EPCs can
      function similarly to arterial endothelial cells and thereby confer longer
      vascular-graft survival. Due to their unique properties, EPCs might have other
      general applications for tissue-engineered structures and in treating vascular
      diseases.

PMID- 11533708
TI  - NSAIDs inhibit alpha V beta 3 integrin-mediated and Cdc42/Rac-dependent
      endothelial-cell spreading, migration and angiogenesis.
AB  - Cyclooxygenase-2 (COX-2), a key enzyme in arachidonic acid metabolism, is
      overexpressed in many cancers. Inhibition of COX-2 by nonsteroidal anti
      inflammatory drugs (NSAIDs) reduces the risk of cancer development in humans and
      suppresses tumor growth in animal models. The anti-cancer effect of NSAIDs seems
      to involve suppression of tumor angiogenesis, but the underlying mechanism is not
      completely understood. Integrin alpha V beta 3 is an adhesion receptor critically
      involved in mediating tumor angiogenesis. Here we show that inhibition of
      endothelial-cell COX-2 by NSAIDs suppresses alpha V beta 3-dependent activation
      of the small GTPases Cdc42 and Rac, resulting in inhibition of endothelial-cell
      spreading and migration in vitro and suppression of fibroblast growth factor-2
      induced angiogenesis in vivo. These results establish a novel functional link
      between COX-2, integrin alpha V beta 3 and Cdc42-/Rac-dependent endothelial-cell
      migration. Moreover, they provide a rationale to the understanding of the anti
      angiogenic activity of NSAIDs.

PMID- 11533709
TI  - Acceleration of intestinal polyposis through prostaglandin receptor EP2 in
      Apc(Delta 716) knockout mice.
AB  - Arachidonic acid is metabolized to prostaglandin H(2) (PGH(2)) by cyclooxygenase
      (COX). COX-2, the inducible COX isozyme, has a key role in intestinal polyposis.
      Among the metabolites of PGH(2), PGE(2) is implicated in tumorigenesis because
      its level is markedly elevated in tissues of intestinal adenoma and colon cancer.
      Here we show that homozygous deletion of the gene encoding a cell-surface
      receptor of PGE(2), EP2, causes decreases in number and size of intestinal polyps
      in Apc(Delta 716) mice (a mouse model for human familial adenomatous polyposis).
      This effect is similar to that of COX-2 gene disruption. We also show that COX-2
      expression is boosted by PGE(2) through the EP2 receptor via a positive feedback
      loop. Homozygous gene knockout for other PGE(2) receptors, EP1 or EP3, did not
      affect intestinal polyp formation in Apc(Delta 716) mice. We conclude that EP2 is
      the major receptor mediating the PGE2 signal generated by COX-2 upregulation in
      intestinal polyposis, and that increased cellular cAMP stimulates expression of
      more COX-2 and vascular endothelial growth factor in the polyp stroma.

PMID- 11533710
TI  - The natural killer T-cell ligand alpha-galactosylceramide prevents autoimmune
      diabetes in non-obese diabetic mice.
AB  - Diabetes in non-obese diabetic (NOD) mice is mediated by pathogenic T-helper type
      1 (Th1) cells that arise because of a deficiency in regulatory or suppressor T
      cells. V alpha 14-J alpha 15 natural killer T (NKT) cells recognize lipid
      antigens presented by the major histocompatibility complex class I-like protein
      CD1d (refs. 3,4). We have previously shown that in vivo activation of V alpha 14
      NKT cells by alpha-galactosylceramide (alpha-GalCer) and CD1d potentiates Th2
      mediated adaptive immune responses. Here we show that alpha-GalCer prevents
      development of diabetes in wild-type but not CD1d-deficient NOD mice. Disease
      prevention correlated with the ability of alpha-GalCer to suppress interferon
      gamma but not interleukin-4 production by NKT cells, to increase serum
      immunoglobulin E levels, and to promote the generation of islet autoantigen
      specific Th2 cells. Because alpha-GalCer recognition by NKT cells is conserved
      among mice and humans, these findings indicate that alpha-GalCer might be useful
      for therapeutic intervention in human diseases characterized by Th1-mediated
      pathology such as Type 1 diabetes.

PMID- 11533711
TI  - Activation of natural killer T cells by alpha-galactosylceramide treatment
      prevents the onset and recurrence of autoimmune Type 1 diabetes.
AB  - Type 1 diabetes (T1D) in non-obese diabetic (NOD) mice may be favored by immune
      dysregulation leading to the hyporesponsiveness of regulatory T cells and
      activation of effector T-helper type 1 (Th1) cells. The immunoregulatory activity
      of natural killer T (NKT) cells is well documented, and both interleukin (IL)-4
      and IL-10 secreted by NKT cells have important roles in mediating this activity.
      NKT cells are less frequent and display deficient IL-4 responses in both NOD mice
      and individuals at risk for T1D (ref. 8), and this deficiency may lead to T1D
      (refs. 1,6-9). Thus, given that NKT cells respond to the alpha-galactosylceramide
      (alpha-GalCer) glycolipid in a CD1d-restricted manner by secretion of Th2
      cytokines, we reasoned that activation of NKT cells by alpha-GalCer might prevent
      the onset and/or recurrence of T1D. Here we show that alpha-GalCer treatment,
      even when initiated after the onset of insulitis, protects female NOD mice from
      T1D and prolongs the survival of pancreatic islets transplanted into newly
      diabetic NOD mice. In addition, when administered after the onset of insulitis,
      alpha-GalCer and IL-7 displayed synergistic effects, possibly via the ability of
      IL-7 to render NKT cells fully responsive to alpha-GalCer. Protection from T1D by
      alpha-GalCer was associated with the suppression of both T- and B-cell
      autoimmunity to islet beta cells and with a polarized Th2-like response in spleen
      and pancreas of these mice. These findings raise the possibility that alpha
      GalCer treatment might be used therapeutically to prevent the onset and
      recurrence of human T1D.

PMID- 11533712
TI  - In vivo optical mapping of epileptic foci and surround inhibition in ferret
      cerebral cortex.
AB  - The population of neurons participating in an epileptiform event varies from
      moment to moment. Most techniques currently used to localize epileptiform events
      in vivo have spatial and/or temporal sampling limitations. Here we show in an
      animal model that optical imaging based on intrinsic signals is an excellent
      method for in vivo mapping of clinically relevant epileptiform events, such as
      interictal spikes, ictal onsets, ictal spread and secondary homotopic foci. In
      addition, a decrease in the optical signal correlates spatially with a decrease
      in neuronal activity recorded from cortex surrounding an epileptic focus. Optical
      mapping of epilepsy might be a useful adjunct in the surgical treatment of
      neocortical epilepsy, which critically depends on the precise localization of
      intrinsically epileptogenic neurons.

PMID- 11533715
TI  - The art and design of genetic screens: yeast.
AB  - Understanding the biology of complex systems is facilitated by comparing them
      with simpler organisms. Budding and fission yeasts provide ideal model systems
      for eukaryotic cell biology. Although they differ from one another in terms of a
      range of features, these yeasts share powerful genetic and genomic tools.
      Classical yeast genetics remains an essential element in discovering and
      characterizing the genes that make up a eukaryotic cell.

PMID- 11533716
TI  - Monogenic causes of X-linked mental retardation.
AB  - Mutations in X-linked genes are likely to account for the observation that more
      males than females are affected by mental retardation. Causative mutations have
      recently been identified in both syndromic X-linked mental retardation (XLMR) and
      in the genetically heterogeneous 'nonspecific' forms of XLMR, for which cognitive
      impairment is the only defining clinical feature. Proteins that function in
      chromatin remodelling are affected in three important syndromic forms of XLMR. In
      nonspecific forms of the disorder, defects have been found in signal-transduction
      pathways that are believed to function during neuronal maturation. These findings
      provide important insights into the molecular and cellular defects that underlie
      mental retardation.

PMID- 11533717
TI  - Http://C. elegans: mining the functional genomic landscape.
AB  - Caenorhabditis elegans is a powerful animal model for the study of functional
      genomics. The completed and well-annotated DNA sequence is available and a
      systematic study of gene function by RNA-interference-mediated knockdown of every
      gene is in progress. Full-genome DNA microarrays and DNA chips can be used to
      determine expression changes at different stages of development and in different
      mutant backgrounds, and a protein-interaction map based on the yeast two-hybrid
      approach is in progress. These high-capacity approaches to studying gene function
      will provide new insights into invertebrate and vertebrate biology.

PMID- 11533718
TI  - Control of developmental timing in animals.
AB  - The molecular mechanisms that time development are now being deciphered in
      various organisms, particularly in Caenorhabditis elegans. Key recent findings
      indicate that certain C. elegans timekeeping genes are conserved across phyla,
      and their developmental expression patterns indicate that a timing function might
      also be conserved. Small regulatory RNAs have crucial roles in the timing
      mechanism, and the cellular machinery required for production of these RNAs
      intersects with that used to process double-stranded RNAs during RNA
      interference.

PMID- 11533719
TI  - Time zones: a comparative genetics of circadian clocks.
AB  - The circadian clock is a widespread cellular mechanism that underlies diverse
      rhythmic functions in organisms from bacteria and fungi, to plants and animals.
      Intense genetic analysis during recent years has uncovered many of the components
      and molecular mechanisms comprising these clocks. Although autoregulatory genetic
      networks are a consistent feature in the design of all clocks, the weight of
      evidence favours their independent evolutionary origins in different kingdoms.

PMID- 11533720
TI  - Quality control in molecular genetic testing.
AB  - DNA-based testing for genetic diseases has developed from nothing into a
      principal part of laboratory medicine over the past 15 years. In the rush to
      bring these powerful new technologies into medical use, issues of quality have
      not always been given sufficient attention. Efforts are now being made to assess
      the quality of the output of genetic testing laboratories, and the results show
      that there is room for improvement.

PMID- 11533721
TI  - The consequences of political dictatorship for Russian science.
AB  - The Soviet communist regime had devastating consequences on the state of Russian
      twentieth century science. Country Communist leaders promoted Trofim Lysenko--an
      agronomist and keen supporter of the inheritance of acquired characters--and the
      Soviet government imposed a complete ban on the practice and teaching of
      genetics, which it condemned as a "bourgeois perversion". Russian science, which
      had previously flourished, rapidly declined, and many valuable scientific
      discoveries made by leading Russian geneticists were forgotten.

PMID- 11533722
TI  - A journey into space.
AB  - The fission yeast, Schizosaccharomyces pombe, has been used as a model eukaryote
      to study processes such as the cell cycle and cell morphology. In this single
      celled organism, growing in a straight line and maintaining the nucleus in the
      centre of the cell depend on intracellular positional information. Microtubules
      and microtubular transport are important for generating positional information
      within the fission yeast cell, and these molecular mechanisms are also probably
      relevant for generating positional information in other eukaryotic cells.

PMID- 11533723
TI  - Multidrug permeases and subcellular cholesterol transport.
AB  - Studies of Niemann-Pick C (NPC) and Tangier diseases have led to the
      identification of the causative genes, NPC1 and ABCA1, respectively.
      Characterization of their protein products shows that NPC1 and ABCA1 are
      permeases that belong to two different superfamilies of efflux pumps, which might
      be important in subcellular lipid and cholesterol transport.

PMID- 11533724
TI  - ATP synthase--a marvellous rotary engine of the cell.
AB  - ATP synthase can be thought of as a complex of two motors--the ATP-driven F1
      motor and the proton-driven Fo motor--that rotate in opposite directions. The
      mechanisms by which rotation and catalysis are coupled in the working enzyme are
      now being unravelled on a molecular scale.

PMID- 11533725
TI  - Evolutionary conservation between budding yeast and human kinetochores.
AB  - Accurate chromosome segregation during mitosis requires the correct assembly of
      kinetochores--complexes of centromeric DNA and proteins that link chromosomes to
      spindle microtubules. Studies on the kinetochore of the budding yeast
      Saccharomyces cerevisiae have revealed functionally novel components of the
      kinetochore and its regulatory complexes, some of which are highly conserved in
      humans.

PMID- 11533726
TI  - Re-evaluating centrosome function.
AB  - Over the past 100 years, the centrosome has risen in status from an enigmatic
      organelle, located at the focus of microtubules, to a key player in cell-cycle
      progression and cellular control. A growing body of evidence indicates that
      centrosomes might not be essential for spindle assembly, whereas recent data
      indicate that they might be important for initiating S phase and completing
      cytokinesis. Molecules that regulate centrosome duplication have been identified,
      and the expanding list of intriguing centrosome-anchored activities, the
      functions of which have yet to be determined, promises continued discovery.

PMID- 11533727
TI  - Birth of a new institute--Biopolis Dresden.
AB  - Molecular cell biology is now facing the challenges of the post-genomic era. In
      this regard, the recently established Max-Planck-Institute of Molecular Cell
      Biology and Genetics in Dresden, Germany, provides interesting perspectives. Its
      atypical structure and the unique mixture of research topics and model systems
      give this Max-Planck-Institute the necessary versatility and flexibility for this
      new phase of biology.

PMID- 11533728
TI  - Claude Bernard: primer of the second biomedical revolution.
AB  - Claude Bernard, the son of a Beaujolais winegrower, moved to Paris to pursue his
      literary ambitions and went on to become one of the fathers of modern life
      sciences. What did Bernard do to earn universal renown? And are his teachings
      relevant to modern science?

PMID- 11533729
TI  - Molecular genetics of cranial nerve development in mouse.

PMID- 11533730
TI  - The cognitive neuroscience of remembering.

PMID- 11533731
TI  - Neural foundations of imagery.

PMID- 11533732
TI  - Cyclic nucleotide-gated channels: shedding light on the opening of a channel
      pore.

PMID- 11533733
TI  - Transcriptional channelopathies: an emerging class of disorders.

PMID- 11533734
TI  - Neurophysiological mechanisms underlying the understanding and imitation of
      action.

PMID- 11533735
TI  - The Cardiovascular Journal of South Africa gains international recognition.

PMID- 11533736
TI  - Waist circumference predicts clustering of cardiovascular risk factors in older
      South Africans.
AB  - OBJECTIVE AND DESIGN: A cross-sectional analytical study to determine the
      cardiovascular risk factor profile of older residents of fishing villages on the
      West Coast of South Africa, and to determine which anthropometric measures are
      associated with risk factors. SUBJECTS: A convenient community-based sample of
      152 subjects of mixed ancestry aged 55 years and over was recruited door-to-door
      using an address list of age-eligible subjects provided by the local public
      health care clinics. METHODS: Cardiovascular relationships were investigated
      between (i) number of risk factors (hypertension, hypercholesterolaemia,
      diabetes) and body mass index (BMI), waist-to-hip ratio (WHR), and waist
      circumference; and (ii) continuous cardiovascular risk factor variables and
      physical activity, smoking, dietary intake, and 24-hour urinary sodium and
      potassium concentrations. RESULTS: The prevalence of hypertension ( > or =160/95
      mmHg) was 74.3% (95% CI: 67.2 - 81.4%). Neither 24-hour urinary sodium nor
      potassium concentrations was associated with blood pressure (BP). Past, but not
      present, moderate-intensity physical activity, particularly that associated with
      occupation, was negatively associated with systolic BP (r = -0.24, P < 0.05). The
      prevalence of diabetes and hypercholesterolaemia (serum cholesterol > or = 6.5
      mmol/l) was 24.6% (95% CI: 17.2 - 32%) and 40% (95% CI: 31.8 - 48.2%),
      respectively. The percentage of subjects with 0, 1, or 2 or more cardiovascular
      risk factors was 13.4%, 44.1% and 42.5%, respectively. Subjects with a waist
      circumference > or = 92 cm had a significantly higher number of cardiovascular
      risk factors than those with a waist circumference < 92 cm ( chi(2) = 9.29, P <
      0.01), and this association remained significant even after controlling for age,
      sex and smoking (P < 0.05). Neither BMI tertiles according to sex, nor a BMI cut
      point > or =30, was significantly associated with a clustering of risk factors.
      CONCLUSION: In a sample of older South Africans of mixed ancestry at high risk of
      cardiovascular disease, waist circumference measuring > or = 92 cm predicts
      clustering of risks factors, independently of BMI. This simple, population
      specific reference value may provide a useful screening tool to identify at-risk
      individuals for targeted prevention for coronary heart disease and associated
      metabolic disorders.

PMID- 11533737
TI  - Biocor No- React stentless aortic valve--short-term results.
AB  - OBJECTIVES: Short-term results of the bioprosthetic Biocor No-React composite
      porcine stentless aortic valve (Biocor Industria e Pesquisas LTDA, Belo
      Horizonte, Brazil) implanted in patients in whom anticoagulation was thought to
      be contraindicated or expected to be non-compliant. METHODS: Retrospective review
      of 52 consecutive prospective patients in whom this valve was implanted, between
      September 1994 and May 1998. RESULTS: Average age was 44 +/- 17 years; 75% of
      patients were operated on for rheumatic heart disease and combined procedures
      were done in 40% of cases. Early mortality was 5.8%, and related to pre-operative
      ejection fraction ( P < 0.03), New York Heart Association (NYHA) class (P <
      0.01), and bacterial endocarditis (P < 0.04). On discharge, 84% of survivors were
      in NYHA class I and 16% in class II. The average postoperative prosthetic valve
      peak gradient on echocardiography was 19.9 +/- 11 mmHg and was related to pre
      operative ejection fraction and smaller valve sizes. Postoperative residual
      trivial or mild aortic regurgitation was seen in 19 patients (36.6%), resolved on
      follow-up in 10 cases, and did not correlate with structural deterioration, re
      operation, mortality, or widening of the non-coronary sinus. The non-coronary
      aortic sinus was widened on closure, because of perceived crowding of the
      adjacent stentless valve commisures, in 52% of cases. This was thought to be
      related to the use of an oblique as opposed to transverse aortotomy. Patient
      survival, inclusive of operative deaths, was 88.5%, and event-free survival was
      80.0% at 4 years. CONCLUSION: The short-term results of this stentless aortic
      valve in a young predominantly third-world population group are acceptable, and
      appear to be superior to the results for mechanical valves in a similar patient
      group. We would recommend a transverse aortotomy above the sinotubular ridge to
      be the more appropriate aortotomy incision when using stentless aortic valves.

PMID- 11533738
TI  - Functional significance of coronary angiography in recognition of residual
      myocardial viability in patients with previous myocardial infarction.
AB  - The relationship between the epicardial blood supply to the akinetic area, its
      'residual myocardial viability' and 'contractile reserve' were the subjects of
      this study involving 29 postinfarct patients with double- or triple-vessel
      coronary disease and ejection fraction less than 45%. Eighty-one of 232 analysed
      segments (34.9%) were akinetic. Nineteen akinetic segments (23.5%) were defined
      as viable and 12 (14.8%) demonstrated residual contractility. The epicardial
      blood flow supply to 32 (39.5%) akinetic segments was moderately decreased, 11
      (34.4%) of them were viable, and 9 (28.1%) demonstrated contractile reserve. The
      epicardial blood flow to 49 (60.5%) akinetic segments appeared severely limited;
      only 8 (16.3%) of them were viable and 3 (6.1( demonstrated contactile reserve.
      The incidence of viability of the akinetic segments was not significantly
      (P<0.061) different in those regions with different epicardial blood supply
      (16.3% v. 34.4%). However, the contractile reserve was significantly (P<0.006)
      more often preserved in akinetic segments with better epicardial blood flow
      (28.1% v. 6.1%). We concluded that the extent of coronary disease defined by
      angiography does not predict residual myocardial viability of the akinetic
      myocardium in postinfarct patients. However, well&hyphen preserved epicardial
      flow is associated with a significantly increased incidence of preserved
      contractile reserve and weakly preserved epicardial flow is associated with a
      very low incidence of contractile reserve in these patients.

PMID- 11533739
TI  - Coronary cameral fistula occurring in a case of Down syndrome.
AB  - This case report describes a coronary cameral fistula, an isolated cardiac
      defect, in a child with Down syndrome. Although Down syndrome patients are known
      to have a high incidence of cardiac defects, to the best of our knowledge this
      particular association has not been described previously.

PMID- 11533740
TI  - Myocardial viability--mechanisms of reversible myocardial dysfunction and
      diagnosis in coronary artery disease.
AB  - The natural history of ischaemic myocardium and numerous revascularisation
      studies have proved that it is clinically important to distinguish viable but
      dysfunctional myocardium from irreversibly injured muscle in patients with
      coronary disease. A large variety of invasive and non-invasive methodologies are
      available for the detection of myocardial viability. This review focuses on the
      value and limitations of the current diagnostic approach to the recognition of
      stunned and hibernating myocardium in the light of the current understanding of
      their pathophysiological mechanisms.

PMID- 11533742
TI  - Trans-nasal route. The new way of upper gastrointestinal technique diagnostic
      endoscopy.

PMID- 11533743
TI  - A case for user charges in public hospitals.
AB  - The present decline in per capita expenditure on health in Saudi Arabia requires
      private funding to reduce pressure of health expenditure on the government
      budget. User charges would be an important source of revenue in the Kingdom where
      services cannot be cut and taxes are not imposed. User charges in public
      facilities would curtail over-utilization and reduce inefficient use of resources
      by providing a link between financial responsibility and the provision of
      services. The financial implication facing patients would encourage them to be
      more cost-conscience, and therefore their physicians would be encouraged to limit
      practices such as over prescribing drugs and the use of highly specialized
      diagnostic procedures for routine investigation or minor illnesses. Lack of
      economic incentives have led to a lack of concern for the cost of medical care.
      User charges would not only encourage both consumers and providers to be cost
      conscious, but would raise revenue to ease pressure on the health budget, combat
      moral hazards and assert priorities. However, to be effective, and in order to
      make a serious impact on the health system, user charges must be extended to all
      government sectors and specialist hospitals and charges must be high enough to
      discourage inappropriate use of services.

PMID- 11533744
TI  - Thalassemia syndromes in Saudi Arabia. Meta-analysis of local studies.
AB  - The geographical distribution of Alpha and Beta-Thalassemias differ markedly.
      Alpha-Thalassemia being particularly prevalent in Southeast Asia and Beta
      Thalassemia in the Mediterranean basin. Thalassemia syndromes are common in Saudi
      Arabia: the Beta-Thalassemia genes occur with variable frequency in different
      regions of Saudi Arabia and both B+ and Bo thalassemia have been reported. Alpha
      Thalassemia is also highly prevalent here and the interaction with the sickle
      cell gene is commonly observed. Over the last few years, a great deal of
      information regarding the clinical, molecular and management of these disorders
      has accumulated in the literature. In this paper we summarize some of the recent
      studies on the subject along with our experience and our attempt to highlight a
      number of questions still awaiting answers.

PMID- 11533745
TI  - Old and new anti-epileptic drugs in pregnancy.
AB  - During the recent years, a significant number of anti-epileptic drugs have been
      approved for prescription in different countries. In addition, some other
      promising drugs are in various stages of development. Soon after each drug has
      found its place in the therapeutic arsenal, pregnancies with exposure occur, with
      an increased risk of birth defect and developmental disturbances. As regards the
      possible teratogenic effect of the new anti-epileptic drugs, apart some
      individual reports we have only the results of pre-clinical toxicological studies
      which are difficult to extrapolate to the human situation, because of the well
      known interspecies differences in pharmacokinetics and pharmacodynamics.
      Furthermore, combinations of anti-epileptic drugs are not tested pre-clinically
      while these new drugs are prescribed as add-on medication. So, metabolic
      interactions between individual components of such drug combinations may induce
      unexpected teratogenic effects. Also as for the teratogenic effects of the  old 
      drugs many questions have still to be defined. The most common and more important
      are which anti-epileptic drugs or combination of drugs is most safe for a
      particular woman with epilepsy and if there is an association between single anti
      epileptic drugs and specific malformations. The reason is that none of the
      available reports to date have studied a sufficient number of women with epilepsy
      exposed to anti-epileptic drug monotherapy during pregnancy. Other questions
      concern dose-effect relationships, a universally accepted definition of major and
      minor malformations, and the lack of a thorough, exhaustive evaluation of the
      other risk factors, apart from the drugs. All these questions need to be
      ascertained for both the old and the new anti-epileptic drugs. Owing to these
      considerations, in 1998 an European Register of anti-epileptic drugs and
      pregnancy was instituted. The primary objective of the study is to evaluate and
      determine the degree of safety, with respect to the human foetus, of anti
      epileptic drugs with reference to both old and new, and to individual drugs and
      drugs in combination. Secondary objectives are to establish the pattern of
      abnormalities, if any, associated with anti-epileptic drugs individually and in
      combination, to delineate drug-specific syndromes, if any, to evaluate dose
      effect relationships. Tertiary objectives are to provide references data for use
      in pre-pregnancy counselling, and for development of guidelines. The evaluation
      of other etiological risk factors is also considered.

PMID- 11533746
TI  - Adolescent endocrinology in Saudi Arabia.
AB  - OBJECTIVE: The importance of providing special health care services for
      adolescents has been recently stressed. In Saudi Arabia, adolescents have no
      special services. In this study, we describe our first 5 years experience of an
      adolescent endocrinology clinic in Security Forces Hospital. We believe it is the
      first clinic with this objective in the Kingdom. METHODS: An adolescent
      endocrinology clinic was run by a team composed of pediatric endocrinologist,
      diabetic nurse educator, clinic nurse and a dietician in collaboration with other
      supportive staff and consultants from other disciplines. The methodology of
      setting up, staffing and running the clinic is described. RESULTS: About 223
      cases were registered over 5 years. The most common problems were short stature
      53 (24%), diabetes mellitus 49 (22%), obesity 40 (18%), thyroid disorders 28
      (13%), delayed puberty 20 (9%) and rickets (8%). The clinic was well accepted by
      parents and their families. We learned a lot on how to handle these problems
      locally. CONCLUSION: Based on our experience, we recommend establishing special
      health care services for adolescents both at the primary care, as well as
      secondary and tertiary care levels.

PMID- 11533747
TI  - Primary hyperparathyroidism and pregnancy.
AB  - OBJECTIVE: The coexistence of primary hyper-parathyroidism and pregnancy is very
      rare worldwide. It carries serious complications to the mother and fetus,
      therefore, early diagnosis and management is of paramount importance. METHODS:
      Over a period of 16 years from 1982-1997, 24 patients with primary
      hyperparathyroidism were identified from the central diagnostic index data base
      of King Khalid University Hospital. Out of these, only 3 women with primary
      hyperparathyroidism complicating pregnancy were identified. RESULTS: All 3 women
      were in the fourth decade. Two of them had coexisting vitamin D deficiency with
      initially normal serum calcium and were misdiagnosed as cases of osteomalacia
      while the third had very high serum calcium on first presentation. A single
      parathyroid adenoma was identified in all 3 patients with 2 undergoing surgical
      removal of the adenoma. The third patient unfortunately had an abortion. The
      babies of the first 2 patients were born healthy with no complications.
      CONCLUSION: Primary hyperparathyridism, even though rare in pregnancy, carries
      risks to the mother and fetus and therefore early screening for asymptomatic
      hyper-parathyroidism in all women of childbearing age and in the early antenatal
      period of pregnant women is recommended.

PMID- 11533748
TI  - Thyroid function in cord blood.
AB  - OBJECTIVE: To determine the biochemical parameters of thyroid function in the
      cord blood of Saudi infants. METHODS: Cord blood samples sent to the Pathology
      Department for screening for congenital hypothyroidism were used to determine the
      reference ranges for thyrotropin, free thyroxine, free triiodothyronine,
      thyroxine-binding globulin and thyroglobulin. All the measurements were carried
      out by immunoassay (Elisa, microparticle enzyme immunoassay or chemiluminescence
      immunoassay). Reference ranges were calculated after exclusion of outliers.
      RESULTS: Reference ranges for thyrotropin, free thyroxine and thyroxine-binding
      globulin were similar to published values, whereas those for free
      triiodothyronine and thyroglobulin were different. CONCLUSION: For correct
      interpretation of the parameters of thyroid function in cord blood it is
      essential to have reference ranges based on the laboratory's current methods and
      derived from the local population.

PMID- 11533749
TI  - Adult bacteremia. Comparative study between diabetic and non-diabetic patients.
AB  - OBJECTIVES: To compare type of infection, microbiology, source, complications and
      outcome of bacteremia in diabetic and non-diabetic patients in our teaching
      hospital. To study the risk factors associated with diabetic bacteremia's
      mortality and to compare our findings with those reported in the literatures.
      METHODS: Retrospective study of all adult cases of bacteremia admitted to King
      Abdulaziz University Hospital, Jeddah, Kingdom of Saudi Arabia, from January 1998
      to January 1999. RESULTS: Rate of bacteremia per 1000 admission was 23. We
      compared 71 episodes in 48 diabetics with 100 episodes in 77 non-diabetics.
      Diabetic patients were older than non-diabetics (mean age 61.08 versus 49.89
      years, p <0.001). No statistically significant difference was found between the 2
      groups in the type and source of infection. Klebsiella of urinary source was
      isolated from 37% episodes in diabetics versus 11% non-diabetics (p 0.03). Acute
      renal failure and septic shock were the 2 complications significantly developed
      in non-diabetics compared to diabetics (19% versus 7% and 13% versus 4%, p=0.02
      and 0.05). Mortality due to bacteremia was 24% in diabetics and 44% in non
      diabetics (p 0.007). Hospital acquired infections, presence of underlying
      malignancy, use of ventilators, development of septic shock and acute renal
      failure, were factors associated with high mortality in diabetic bacteremia.
      CONCLUSION: Our results are comparable with those reported in the literatures.
      The better outcome observed in our diabetic bacteremia could be due to adequate
      glycemic control during bacteremic episode and appropriate choice of empiric
      antibiotics.

PMID- 11533750
TI  - Effect of chromium supplementation on glucose tolerance and lipid profile.
AB  - OBJECTIVES: To investigate chromium status of the adult population in the western
      region of Saudi Arabia and the possibility of using serum chromium status
      measurement as indicator of this status. METHODS: The effect of chromium
      supplement on glucose tolerance and lipid profile was studied in 44 normal, free
      living adults. 200mg chromium/day as CrCL3 or a placebo was given in a double
      blind cross-over study, with 8 weeks experimental periods. Fasting, 1 hour and 2
      hour post glucose challenge (75 g of glucose) glucose, serum fructosamine, total
      cholesterol, high-density lipoprotein-cholesterol, triglycerides, chromium and
      dietary intakes were estimated at the beginning and the end of each stage.
      RESULTS: Mean serum chromium increased significantly after supplement (P<.001)
      indicating proper absorption of the element. Supplement did not effect the total
      cholesterol, however, the mean high-density lipoprotein-cholesterol level was
      significantly increased (P<.001), the mean triglycerides levels significantly
      decreased (P<.001), and the mean fructosamine level significantly decreased
      (P<.05). In addition, chromium supplement effected 1 hour and 2 hour post glucose
      challenge glucose levels in subgroups of subjects with 2 hour glucose level > 10%
      above or below fasting level and significantly differing to it (P<.05 in both
      cases), by decreasing or increasing them significantly (P<.05 in all cases) so
      that the 2 hour mean became not significantly different to the fasting mean.
      Since no significant changes in weight, dietary intake or habits were found, and
      placebo had no effect, all noted biochemical changes were attributed to chromium.
      CONCLUSION: Improved glucose control, and lipid profile following chromium
      supplement suggests the presence of low chromium status in the studied
      population. However, serum chromium could not be recommended for use as an
      indicator of chromium status as subjects with widely varying levels responded
      favorably to the chromium supplement.

PMID- 11533751
TI  - Substance dependence. A hospital based survey.
AB  - OBJECTIVE: To collect basic data on multiple and diverse issues such as drugs of
      dependence, smoking, initiation age, injection related harm, nutritional status,
      trauma, accidents, abnormal laboratory parameters and co-morbid conditions.
      METHOD: Seven hundred and ninety nine subjects from a voluntary detoxification
      unit were studied. Four hundred and ninety seven charts from June 1995 to
      December 1995 were reviewed retrospectively. For the other 302 subjects admitted
      between September 1996 to December 1996, information regarding drug use, smoking,
      trauma, accidents and co-morbid conditions was recorded during the admission
      interview while the remaining data was later obtained from the charts. RESULTS:
      Sixty eight percent were under 35. Ninety seven percent were smokers and 55%
      started smoking before the age of 15. Sixty four percent initiated drugs before
      the age of 25 while 34% had been on drugs for less than 5 years. Eighty seven
      percent were using heroin or alcohol. Fourteen percent were dependent on more
      than one drug. Among heroin users 91% were injecting, 21% had injection related
      complications, 69% had Hepatitis C Virus and 0.40% died. Forty four percent had
      at least one current medical disorder, 59% had one abnormal laboratory parameter
      and 21% below normal Body Mass Index. Nine percent had mental disorders and 1%
      presented with overdose. Twenty nine percent reported unintentional injuries and
      12% reported of road traffic accidents. Seventeen point five percent had family
      history of drug use, 4.5% had mental disorders and 87% physical disorders.
      CONCLUSION: More accurate and reliable data is required. Current services need to
      be improved. Preventative measures should focus on early detection and
      intervention and a central body for information collection should be established.

PMID- 11533752
TI  - Hearing loss in a textile factory.
AB  - OBJECTIVE: To compare the prevalence rate of hearing loss at different levels of
      noise in a textile factory and to find out the levels of hearing loss according
      to duration (years) of employment in the factory. METHODS: Seventy workers
      exposed to different levels of noise were matched with 70 persons in the
      community who were not exposed to occupational noise. Noise levels dB(A) were
      measured at different locations in the factory. Hearing was assessed in all
      participants. Few cases were excluded from the study because hearing loss was due
      to factors other than exposure to noise. RESULTS: The prevalence rate of hearing
      loss was higher among the exposed group ie. 30% in the exposed group and 8% in
      the non-exposed group. Hearing loss increased with increasing level of noise
      reaching 73% in the 95dB(A) area. Average hearing loss was highest amongst those
      who were employed for 25 years or more, reaching 39% dB(HL). CONCLUSION: The
      findings of this study highlighted the magnitude of the problem, the necessity of
      the application of preventive measures and the need for more studies in this
      field.

PMID- 11533753
TI  - X-linked adrenoleukodystrophy. The Saudi experience.
AB  - OBJECTIVES: To evaluate the clinical, biochemical, neuroradiological, and
      neurophysiological findings of patients with X-linked adrenoleukodystrophy.
      METHODS: Retrospective study evaluating the data of 10 X-linked
      adrenoleukodystrophy patients diagnosed at King Faisal Specialist Hospital and
      Research Centre, Riyadh, Saudi Arabia. RESULTS: The common presenting symptoms
      were deterioration in school performance, vision and hearing, behavioral changes,
      and seizures. Eight patients survived 1-4 years and one patient 12 years after
      the initial presentation, while one patient expired. Six patients had the
      childhood form, 3 had the adolescent form and one had the adrenomyeloneuropathy
      form. Six are in an advanced stage of the disease and 3 have mild to moderate
      spasticity. All except 2 manifested moderate to severe dementia with variable
      degrees of visual loss. Decreased hearing and features of adrenal insufficiency
      were seen in 7 patients. Very long chain fatty acids were significantly increased
      in seven and mildly elevated in 2 patients, however the C26 to C22 ratio was
      increased in all. The characteristic high-signal intensity of parieto-occipital
      white matter on brain magnetic resonance imaging T2-weighted images was observed
      in all patients. Two patients had functional study of the brain, which showed
      hypometabolic activity in gray and white matter of the occipital lobes. Various
      neurophysiological abnormalities were detected. The response to different
      treatment modalities was not promising. CONCLUSION: The disease is more common
      than had been previously recognized due to phenotypic variability and a wide
      spectrum of presentations. This report describes various aspects of this disorder
      and emphasizes the importance of early identification and treatment of
      asymptomatic but biochemically affected individuals, since all current
      therapeutic approaches are disappointing if overt neurological abnormalities have
      been already developed.

PMID- 11533754
TI  - Parkinson's disease. Clinical and electrophysiological evaluation.
AB  - OBJECTIVES: Identification of the clinical spectrum and the electrophysiological
      responses of a Saudi population with Parkinson's disease as opposed to a matched
      normal population. METHODS: Fifty four subjects (41 males and 13 females) were
      selected for the study. The patients were clinically evaluated for the occurrence
      of Parkinson's disease symptoms, as well as other associated medical conditions.
      All patients had brain computerized tomography scans. Electrophysiological tests
      were performed on all patients using the Medelec ST 10 Sensor 59394 Model. These
      tests included somatosensory evoked response of median nerves, brain stem
      auditory evoked responses and visual evoked responses. The significant
      differences in these evoked responses between the patients with Parkinson's
      disease and normal patients were statistically evaluated. RESULTS: Twenty six out
      of the 40 computerized tomography brain scans which had been carried out showed
      normal brain morphology and 5 had a clear evidence of cerebrovascular disease
      while only 9 showed distinctive brain atrophy. The mean values for the brain stem
      auditory evoked response, the somatosensory evoked response and the visual evoked
      responses were higher in patients with Parkinson's disease as compared to those
      who did not have the disease. Significant differences were only seen as prolonged
      latencies in median nerve somatosensory evoked response, as well as delayed waves
      I and V on the brain stem auditory evoked response. Inter-wave latencies,
      however, were not significantly different. CONCLUSION: Parkinson's disease in a
      Saudi population showed significant differences to somatosensory evoked response
      and brain stem auditory evoked response electrophysiological data as compared to
      age-matched controls, however, the clinical characteristics of Parkinson's
      disease in Saudi patients are not significantly different from those reported for
      patients elsewhere.

PMID- 11533755
TI  - Smoking habits of students in College of Applied Medical Science, Saudi Arabia.
AB  - OBJECTIVE: To establish a baseline data on the smoking habits of health science
      students in a Saudi Arabian university environment. METHODS: The participating
      subjects were students of the College of Applied Medical Sciences within the age
      range of 18 to 26. An experimental design with pre-structured questionnaires, and
      simple random sampling was administered to 712 participants by a panel of experts
      in behavioral health sciences. RESULTS: Out of 647 respondents, 186 (29%) were
      current smokers. Of those that indicated that they were currently smokers, 127
      (20%) were male and 59 (9%) were female. The 20-24 year old age group exhibited
      the highest prevalence of smoking (P<0.000). Major factors influencing the
      smoking prevalence were the smoking habits of peers, siblings, and parents
      (P<0.005). Most of the respondents appeared to be  Light Smokers , consuming less
      than 10 cigarettes per day. When asked of their awareness of the health hazards
      of smoking, 73% of the respondents answered that they were aware of the hazards.
      Of those that smoked, 70% expressed a desire to cease cigarette smoking. Media
      influence was considered to be the major source of information on the health
      consequences of cigarette smoking. CONCLUSION: Cigarette smoking is prevalent
      among students of health care professionals. Author advocates a collaborative
      effort in order to alleviate the consequences of cigarette smoking among health
      professionals. This effort must embody a multidisciplinary approach that includes
      legislators, mass media, public education and health professionals at all levels.

PMID- 11533756
TI  - Prevalence of food allergy in asthmatic patients.
AB  - OBJECTIVES: This study was conducted to assess the role of clinical sensitivity
      to food on the pattern of bronchial asthma. METHODS: A total of 1341 patients
      with asthma were included in the present study. The clinical sensitivity to food
      and its relation to respiratory symptoms were assessed cross-sectionally (using
      detailed questionnaires), and longitudinally during their regular visits to the
      asthma clinic using diet diary. Total IgE was determined for a subsample of the
      patients (No = 392). RESULTS: The prevalence of clinical sensitivity to food was
      29%; about 2 thirds of the patients had high total IgE level. Asthmatic patients
      with clinical sensitivity to food present with some particular features which are
      considered risk factors that determine the occurrence and clinical pattern of
      asthma. In addition, some personal characteristics in the asthmatic patients make
      them at increased risk to have clinical sensitivity to food. CONCLUSION: From the
      clinical experience of asthma management in our clinic, the authors believe and
      emphasize that elimination of food items from the diet of an asthmatic patient
      should be considered after careful investigation and observation of the patient.
      In addition, some personal characteristics in the asthmatic patients make them at
      increased risk to have clinical sensitivity to food. Early detection of food
      allergy is an important preventive factor for food related respiratory symptoms.
      The natural course of food allergy is of resolution over time although this may
      differ between foodstuffs and may be variably affected by avoidance of the
      offending allergen.

PMID- 11533757
TI  - An unusual association between oral sarcoma and bulbar palsy.
AB  - A 90 year old male presented with symptoms and signs of right lower cranial
      nerves palsy. A small mass was found on the right side at the back of his mouth.
      Light microscopy and histoimmunochemical studies of the biopsy of the mass showed
      an alveolar soft part sarcoma arising from the right myohyoid muscle. The unusual
      location and presentation of this rare tumor is discussed.

PMID- 11533758
TI  - Visual loss after coronary artery bypass surgery.
AB  - Anterior ischemic optic neuropathy is caused by microvascular occlusion of the
      prelaminar or laminar portion of the optic nerve head. The main types are
      arteritic, non-arteritic, and autoimmune. Few cases were reported following
      coronary artery bypass surgery. A 63-year-old man, who is both diabetic and
      hypertensive, underwent coronary artery bypass graft complicated postoperatively
      by sudden visual loss in his right eye. The diagnosis was non-arteritic anterior
      ischemic optic neuropathy. Possible predisposing factors were crowded disc and
      internal carotid artery stenosis.

PMID- 11533759
TI  - Schmidt's syndrome in a Saudi family.
AB  - We present 3 patients from a Saudi family who are presented with polyglandular
      autoimmune syndrome type 2. They have Addison's disease with either autoimmune
      thyroid disease or insulin dependent diabetic mellitus. Although this syndrome is
      rare, the incidence among Saudi Arabia or the Arab population is not known.

PMID- 11533760
TI  - Thyroiditis induced by interferon in dialysis.
AB  - We describe a dialysis patient who acquired acute Hepatitis C infection. Her
      primary renal disease was systemic lupus erythromatosis. She was having goitre
      but clinically euthyroid and her thyroid function test was normal. To avoid long
      term complications of Hepatitis C we elected to treat her with Interferon 3
      million units subcutaneously 3 times a week. During treatment she developed some
      transient side effects initially which subsided but later she felt pressure
      symptoms around her neck. When we checked her TSH and thyroid antibodies these
      were elevated. Though this could be related to HCV, rarely, but we think the
      thyroid change is mostly related to Interferon. Some possible explanation of the
      effect of Interferon on thyroid have been reviewed and we think patients getting
      such drugs should be under close monitoring to avoid permanent thyroid
      dysfunction.

PMID- 11533761
TI  - Spontaneous intraperitoneal expulsion of an unruptured hydatid cyst.
AB  - We report a 43-year-old man with a 20 x 20 cm hydatid cyst, spontaneously
      extruded out from the left lobe of the liver. This complication of hydatid cyst
      has not been recorded earlier, and makes the case unique in itself and worth
      reporting. The patient presented with a rare complication of biliary peritonitis
      of hydatid disease.

PMID- 11533762
TI  - Clinical features versus laboratory values. An infant with transient neonatal
      hypothyroidism.

PMID- 11533763
TI  - Aetiology of community acquired pneumonia: fashionable or familiar.

PMID- 11533764
TI  - Primary malignant lymphoma of bone.

PMID- 11533765
TI  - Hysterectomy--A female gynecologist's perspective.

PMID- 11533766
TI  - Drug addiction.

PMID- 11533767
TI  - Concordant expression of Hirschsprung's disease in monozygous twins.
AB  - A monozygous pair of twins with long segment Hirschsprung's disease born to non
      consanguineous parents is presented. Mother's history was uneventful. In the
      absence of prenatal and postnatal illness, the concordant lesions in this pair
      could be attributed to genetic factors.

PMID- 11533768
TI  - Continuous quality improvement. A proposal for Arabian Gulf Medical Associations.
AB  - Having well-established and active medical associations in the Arabian Gulf
      countries is a promising event. Ideally, however, it must be assured that these
      associations are efficiently and effectively functioning in a manner designed to
      serve the ultimate goal of promoting the standards of the medical profession and
      thus, the quality of health care in the region. This paper is designed to promote
      the application of Continuous Quality Improvement principles by the medical
      associations in the Arabian Gulf. The paper is presented in a general format so
      as to allow for appropriate modifications according to the specific objectives of
      different medical associations. The indicators identified in this proposal to
      assess the quality of structure, process or outcome are not intended as a
      comprehensive list. Rather, the authors aim at establishing a framework on which
      various fine-tuned and appropriately tailored systems can be based.

PMID- 11533769
TI  - Childhood enuresis. Epidemiology, pathophysiology and management.
AB  - The goal of this article is to review childhood enuresis, which is a common
      behavioral condition reported in millions of children worldwide. An online
      computer search was made, and the literature up to 1997 was screened in order to
      include relevant data for this review. The prevalence of childhood enuresis
      varies across reviewed studies. This was attributed to a variety of
      sociodemographic and cultural dynamics of societies. Similarly, the
      pathophysiology of this ubiquitous symptom is determined by multiple risk factors
      including biological, psychological, social, and cultural, but the
      developmental/maturational delay influenced by genetics remains the most
      plausible explanation. Although a variety of pharmacological and non
      pharmacological treatment modalities are traced in the literature, there is yet
      no agreement on a single strategy. A general agreement about behavioral therapy
      as the first choice of treatment of this minor malady began to emerge.
      Additionally, tricyclic antidepressants are the most frequently prescribed drugs
      for the treatment of childhood enuresis. Enuresis is a pediatric public health
      problem and concerted efforts at all levels, ie, professional, promotional,
      educational and public should be made to address its multiple domains such as
      preventive, etiological and curative.

PMID- 11533770
TI  - The use of rectal diclofenac for post-cesarean analgesia.
AB  - OBJECTIVE: To determine whether the prophylactic use of rectal diclofenac sodium
      produces effective analgesia after cesarean section. METHODS: A randomized single
      blind controlled trial. The study period was from September 1997-April 1998.
      Forty patients undergoing both emergency and elective cesarean section were
      studied, with 20 patients in each arm. The study group received 100 mg rectal
      diclofenac immediately after cesarean section followed by 50 mg at 12 hours and
      100 mg at 36 hours after the surgery. The control group did not receive any
      diclofenac suppositories. RESULTS: The results showed that the visual analogue
      score for pain in the study group was significantly less at 12, 18 and 24 hours
      after surgery (P <0.05). The amount of pethidine consumed was also significantly
      less (P <0.05) with 28 injections consumed in the study group as compared with 52
      in the control group (each pethidine injection = 100 mg). The incidence of
      sedation and constipation was significantly less (P<0.05) in the study group.
      However, the incidence of nausea and post-operative pyrexia was comparable in the
      2 groups. CONCLUSION: Rectal diclofenac provides effective analgesia when given
      after cesarean section. It also reduces the patients opioid requirements with a
      corresponding reduction in the opioid related side-effects.

PMID- 11533771
TI  - Consanguinity, fertility, reproductive wastage, infant mortality and congenital
      malformations in Jordan.
AB  - OBJECTIVES: Consanguinity is a wide spread practice in Jordan. The objective of
      this study is to explore the health effects of consanguinity, in particular
      fertility, reproductive wastage, infant mortality and congenital malformations.
      METHODS: A stratified 2 stage cluster sample of 1867 married couples,
      representative of all population groups and all geographic locations of Jordan
      were randomly selected. A questionnaire was specially designed to explore each of
      the objectives set for the study and was field tested. A group of field workers
      were thoroughly trained on the implementation of this instrument. All 1867
      couples were interviewed by these field workers and completed questionnaires were
      reviewed before data entry. Data analysis was carried out using SPSSX statistical
      package. Significance tests were performed wherever appropriate. RESULTS: The
      study showed that fertility, as measured by the number of pregnancies, taking
      into consideration marriage duration, was not affected by consanguinity. Twin
      pregnancies and abortions did not show any significant difference between
      consanguineous and non-consanguineous marriages. Consanguineous marriages showed
      significantly higher rates of still births and infant mortality in general.
      Within the consanguineous group, female infant mortality rates were significantly
      higher than those of males. Congenital malformations as reported by mothers of
      consanguineous marriages were significantly higher than those reported by mothers
      of non-consanguineous marriages. CONCLUSION: This study showed that consanguinity
      has a detrimental effect on many aspects of reproductive health.

PMID- 11533772
TI  - Screening for gestational diabetes mellitus in pregnant females.
AB  - OBJECTIVES: To evaluate the applicability of the 50-g glucose challenge test as a
      screening test for gestational diabetes mellitus in relation to pregnancy
      outcomes. METHODS: A prospective study was conducted on 818 Saudi pregnant
      females who were randomly recruited from the Antenatal Clinics at King Abdulaziz
      University Hospital and New Jeddah Clinic Hospital, Jeddah. All females underwent
      a 50-g glucose challenge test between 24-28 weeks gestation. A result for 50-g
      glucose challenge test was considered positive at > 7.2 mmol/L and the female was
      asked to undergo a 100-g oral glucose tolerance test. The diagnosis of
      gestational diabetes mellitus was carried out according to the National Diabetes
      Data Group criteria. RESULTS: A total of 289 females exhibited plasma glucose
      level > 7.2 mmol/L following the 50-g glucose challenge test. Of the 289 females
      enrolled for the 100-g oral glucose tolerance test, 102 were diagnosed to have
      gestational diabetes mellitus (positive oral glucose tolerance test) and 187 were
      considered oral glucose tolerance test negative according to the National
      Diabetes Data Group diagnostic criteria. This gave a prevalence of gestational
      diabetes mellitus of 12.5%. Gestational diabetes mellitus females were
      significantly older in age, heavier in weight, with higher gravidity, greater
      percentage of operative deliveries and still-births, and heavier fetal birth
      weight as compared with the non-gestational diabetes mellitus group (P<0.05 in
      each case). The maximum sensitivity and specificity of the 50-g glucose challenge
      test were found to be at plasma glucose value of 7.8 mmol/L post the 50g glucose
      load. The sensitivity and specificity of this value was 88% and 84%, with a
      positive predictive value of 82%. To determine whether the values of plasma
      glucose after a 50-g glucose load were detecting abnormalities similar to those
      detected according to that of oral glucose tolerance test; the values obtained
      one-hour post the 50-g glucose challenge test were compared with zero-, one-, 2-
      and 3-hour values and also the area under the curve in the 100-g oral glucose
      tolerance test. Plasma glucose post the 50-g glucose challenge test showed marked
      correlation with oral glucose tolerance test results. This was mostly occurring
      at the one- and 2-hour oral glucose tolerance test values and was stronger in the
      gestational diabetes mellitus group and in both the gestational diabetes mellitus
      plus negative oral glucose tolerance test combined, than in the negative oral
      glucose tolerance test group on its own. CONCLUSION: It is concluded that plasma
      glucose level measured one-hour post a 50-g glucose challenge test at 24-28 weeks
      of gestation with a cut-off value of 7.8 mmol/L is a reliable screening test for
      gestational diabetes mellitus in the local population studied. This test offers
      the best combination of ease and economy of use and reproducibility in screening
      for gestational diabetes mellitus.

PMID- 11533773
TI  - Diabetes and perinatal loss. A continuing problem.
AB  - OBJECTIVE: To determine the fetal outcome in diabetic pregnant patients managed
      exclusively by the obstetrician at King Faisal Military Hospital in the south
      west region of Saudi Arabia, and to compare this with the non-diabetic control
      group in the same hospital. METHODS: Case-control study of 83 diabetic and non
      diabetic pregnant patients who delivered at King Faisal Military Hospital over a
      2 year period. RESULTS: The perinatal mortality rate in diabetic patients was
      6.02% while that in the non-diabetic control group was 1.2%. However, the
      difference was not statistically significant, p>0.05. There was a difference in
      the mean birth weight between the cases and controls; p = 0.001 and the cesarean
      section rate was 5 times higher in the cases than in controls [corrected]. This
      was statistically significant; OR=5.22 (1.90-16.48). CONCLUSION: Diabetes in
      pregnancy is still a major cause of perinatal loss in our community. The increase
      in cesarean section in diabetic pregnant patients also indicates a drain in the
      financial resources. It is recommended that emphasis should be placed on health
      education in order to reduce the cost of child birth as this condition may be
      prevented.

PMID- 11533774
TI  - Congenital paraesophageal hernia in infancy and childhood.
AB  - OBJECTIVES: Congenital paraesophageal hernia is a rare condition in the pediatric
      age group. The symptomatology of these patients is usually non-specific in the
      form of repeated attacks of chest infection and/or recurrent attacks of vomiting
      but can be associated with serious complications such as intrathoracic gastric
      volvulus. METHODS: Between 1989 and 1997, 6 children with paraesophageal hernia
      were treated at our hospital. RESULTS: Six children (4 males and 2 females) were
      treated for congenital paraesophageal hernia. Their age at presentation ranged
      from 2 days to 21/2 years (mean 1.3 years). Two presented with recurrent chest
      infection, while 3 others had recurrent attacks of vomiting with fullness and
      pain in the epigastrium in one of them. One of our patients presented acutely
      immediately after birth with respiratory distress while another was found to have
      intrathoracic gastric volvulus. Chest x-ray was suggestive of paraesophageal
      hernia in all of them but the diagnosis was confirmed by Barium swallow and meal.
      Intraoperatively there was a hernial sac in all of them. The surgical treatment
      consisted of excision of the hernial sac after reducing the stomach and
      tightening of the crura of the esophageal hiatus. Nissen's fundoplication was
      added in 3 patients, but in one of them this was dismantled because of tight
      repair. Anterior and fundal gastropexy was added in one patient, while 2 had
      tightening of the crura only. CONCLUSION: Congenital paraesophageal hernia,
      although rare in the pediatric age group, can present acutely with respiratory
      distress or intrathoracic gastric volvulus. Physicians caring for these patients
      should be aware of such a presentation and complication and paraesophageal hernia
      should be included in the differential diagnosis of children with repeated
      attacks of chest infection and/or vomiting. The rarity of this condition in
      children makes it difficult to evaluate the true necessity of adding an
      antireflux procedure in these patients. We feel some form of gastropexy may be a
      more appropriate procedure to be added to the repair.

PMID- 11533775
TI  - Survival pattern among extreme preterm infants.
AB  - OBJECTIVE: To look at the survival pattern of extreme preterm Omani infants (23
      26 weeks gestation) and compare it with the western countries. METHODS: All
      extreme preterm Omani infants (gestational age of 23 to 26 weeks) admitted from
      November 1991 to February 1998 at the Neonatal Intensive Care Unit of Sultan
      Qaboos University Hospital were reviewed. The detailed records of the infants,
      including name of mother, age, gravidity, parity, route of delivery, Apgar score,
      time of birth, inborn or outborn, birth weight, gestational age, sex, need for
      resuscitation, course in the Neonatal Intensive Care Unit, admission and
      discharge diagnosis, and outcome were collected from the register. The infants
      were stratified according to the gestational age and then analyzed for the
      survival rate among the different gestational ages. RESULTS: A total of 32
      extreme preterm infants were admitted to the Neonatal Intensive Care Unit of
      Sultan Qaboos University Hospital from November 1991 to February 1998. The mean
      birth weight of the cohort was noted to be 798+123 gram (Range 480-1015 grams).
      The mean gestational age was noted to be 25.5+0.95 weeks (Range 23-26 weeks). An
      equal number of males and females were noted in the cohort, with male to female
      ratio of 1:1. A total of 13 infants survived out of 32 infants. The overall
      survival rate for the cohort was noted to be 41%. For the present study, the
      western statistics are averaged and than compared with the Omani statistics. The
      survival rate for western 26 week preterm infants was (on average) 61% as
      compared to 44% among Omani preterm infants. The same trend of low survival was
      noted for 23 and 24 week Omani infants, except for only one 25 week infant.
      CONCLUSION: The significant lower survival rate suggests the need for more
      attention and improvement in the management and care provided to the extreme
      preterm Omani infants.

PMID- 11533776
TI  - Staphylococcus aureus bacteremia.
AB  - OBJECTIVES: To study the episodes of Staph.aureus bacteremia diagnosed at King
      Abdulaziz University Hospital, to determine the source of infection, risk
      factors, the outcome of treatment and to compare our results with those reported
      in the literature. METHODS: A retrospective study in which the episodes of
      Staph.aureus bacteremia diagnosed at King Abdulaziz University Hospital, Jeddah,
      Kingdom of Saudi Arabia in the period from June 1996 to December 1998 were
      analyzed. RESULTS: A total of 103 episodes of Staph.aureus bacteremia were
      diagnosed in 95 patients with a mean age of 33.61 years (range 2 months to 90
      years) and male:female ratio of 1.9:1. More than 50% of patients were Saudi
      nationals. Hospital-acquired infection was detected in 74% of the episodes versus
      25% community-acquired. Methicillin resistant Staph.aureus was found in 29% of
      the episodes. Intravenous catheters and wounds were the main sources of
      bacteremic episodes (29% and 21%). The overall mortality was 32% with significant
      association with old age, diabetes mellitus and hemodialysis for renal failure.
      Risk factors such as surgical wounds, diabetes mellitus and malignancy, were more
      frequently associated with hospital-acquired than community-acquired bacteremia.
      Infective endocarditis was higher in patients with community-acquired bacteremia
      who had unknown source of infection. CONCLUSIONS: As discussed in the text, our
      results are comparable with those reported in the literature. Insertion of
      intravenous catheters under aseptic precaution, better care and judicious
      limitation of patients length of exposure to central line, in addition to proper
      wound dressings could reduce the frequency of blood stream infections.

PMID- 11533777
TI  - Measles antibody titre in children up to 5 years of age in rural areas of Aligarh
      District, India.
AB  - OBJECTIVE: To determine the pattern of decline of maternal antibodies in 0-9
      month old infants and to study the prevalence of measle antibodies and their
      levels in 9 month to 5 year old children, regardless of their immunization
      status. METHODS: A cross-sectional study covering 456 children in the 0-5 year
      age group residing in 9 registered villages in a rural area of Aligarh District
      was conducted. The study included the interview of parents, clinical examination
      of children, and Hemagglutination Inhibition Test for Measles Antibody Titre.
      RESULTS: There was rapid decline in seropositivity from 100% in the 0-3 month age
      group to 18% in the 6-9 month age group. There was a positive correlation (r =
      0.77) between decline of seropositivity and age. Measle immunization coverage
      rate was 64.5%. In 202 children where immunization was confirmed by availability
      of card, sero-conversion was 96.5%. Of the 118 unvaccinated children, 9% were
      sero-positive. Of the 71 children who had a history of measles infection, 75%
      were seropositive indicating correct identification of measle infection by the
      parents.

PMID- 11533778
TI  - Clinical profile of sleep apnea syndrome. A study at a university hospital.
AB  - OBJECTIVES: To review a series of patients with sleep apnea syndrome, to promote
      more awareness and alert local health professionals to early diagnosis and
      treatment. METHODS: We studied, prospectively, 48 consecutive patients who were
      managed at the university hospital from 1992 to 1996. RESULTS: The male:female
      ratio was 1.4:1. The mean interval between onset of symptoms and the diagnosis
      was 5.5 years (range 0.25 to 30). In over half of the patients the diagnosis was
      not suspected upon referral. The mean body mass index was 42.8 kg/m2, (range 25
      to 76). Daytime hypoxemia was present in 28 patients (58%), while 26 (54%) had Pa
      CO2 > 45 mmHg, mainly as a result of obesity-hypoventilation syndrome.
      Significant proportions had systemic and pulmonary hypertension (60% and 23%),
      and 32% had ischemic heart disease. All patients, but one, tolerated continuous
      positive airway pressure, but cost of the equipment led some to prefer surgical
      treatment that is offered free. CONCLUSION: This series shows a bias towards
      female sex and frequent association with obesity-hypoventilation syndrome. In
      many cases the diagnosis was not suspected suggesting poor recognition and
      awareness of sleep apnea syndrome. Monitoring pulse oximetry during sleep was
      helpful in the diagnosis and titration of continuous positive airway pressure.
      Ways of providing continuous positive airway pressure under the health system
      need to be studied.

PMID- 11533779
TI  - Lipid peroxidative damage in the erythrocytes and elevation of serum LDL
      cholesterol, apolipoprotein-B, ferritin and uric acid with age and in coronary
      heart disease patients.
AB  - OBJECTIVES: To determine the normal serum levels of LDL-cholesterol,
      apolipoprotein-B, ferritin, uric acid, and the extent of erythrocytes lipid
      peroxidation in healthy control group subjects and to compare them with coronary
      heart disease patients. Secondly, to study the effects of age and sex on these
      parameters. METHODS: The blood samples from 150 healthy Libyan control group
      subjects (110 men and 40 women) were classified into 3 groups according to their
      age. Group I consisted of 76 subjects with an age range from 20 to 35 years.
      Group II consisted of 45 subjects with an age range from 36 to 50 years. Group
      III consisted of 29 subjects with an age range from 51 to 74 years. The blood
      samples from these groups were analyzed for LDL-cholesterol, apolipoprotein-B,
      ferritin and uric acid levels. Lipid peroxidation was compared in the
      erythrocytes of 56 selected healthy control group subjects (31 men and 11 women)
      of the aforementioned age groups. RESULTS: These parameters have shown age
      dependent elevation in their levels. Meanwhile, LDL-cholesterol and
      Apolipoprotein-B levels in female subjects were higher than those of males.
      However, lipid peroxidation in the erythrocytes has revealed a statistically
      significant increase with increasing age. The comparison between 93 selected, sex
      and age matched, healthy control group subjects with 87 selected coronary heart
      disease patients (55 men and 45 women) with an age range from 30 to 74 years
      (49.6+13.25) has demonstrated significantly higher concentration of LDL
      cholesterol, Apolipoprotein-B, ferritin and uric acid in coronary heart disease
      patients than those of healthy control group subjects. Meanwhile, lipid
      peroxidation was also significantly enhanced in coronary heart disease patients
      compared with healthy control group subjects. CONCLUSION: Our study has revealed
      that an increase in the lipid peroxidation in erythrocytes with age and during
      coronary heart disease, makes red cell membranes more vulnerable to free radical
      damage via formation of reactive oxygen species. It is thus likely that
      peroxidative damage may be contributing to an increase in serum LDL-cholesterol,
      Apolipoprotein-B, probably after its oxidative modification, increase in ferritin
      and hyperuricemia in coronary heart disease patients.

PMID- 11533780
TI  - Hypertension and its relation to renal function 10 years after pregnancy
      complicated by pre-eclampsia and pregnancy induced hypertension.
AB  - OBJECTIVE: To assess the development of hypertension and its relation to renal
      function 10 years after pregnancy complicated by pre-eclampsia and pregnancy
      induced hypertension. METHODS: Women with pre-eclampsia (n=47), pregnancy induced
      hypertension (n=54) or normotensive (n=46) during 1988 were reviewed at King
      Hussein Medical Center, Amman, Jordan, for the development of hypertension and
      renal disorder. Their renal function was reviewed by measuring blood levels of
      urea, uric acid, creatinine, calcium and albumin. Urine was examined for
      microalbuminuria. RESULTS: Women with pre-eclampsia and pregnancy induced
      hypertension had a higher risk of developing hypertension 10 years later compared
      to the control group, (23% for pre-eclampsia, and 39% for pregnancy induced
      hypertension vs. 3% for control). Albumin corrected calcium levels were
      significantly higher in patients with history of pre-eclampsia (2.41 mmol/l) and
      pregnancy induced hypertension (2.42 mmol/l) vs. control (2.33 mmol/l) as well as
      a significant difference in microalbuminuria levels (23% in pre-eclampsia, and
      16% in pregnancy induced hypertension vs. 3% in control). Serum urea, creatinine
      and uric acid levels were not significantly affected (4.4 mmol/l in pre
      eclampsia, 4.7 mmol/l in pregnancy induced hypertension and 4.6 mmol/l in control
      for urea, 76.0 mmol/l in pre-eclampsia, 74.0 mmol/l in pregnancy induced
      hypertension and 77.0 mmol/l in control for creatinine and 252.0 mmol/l in pre
      eclampsia, 250.0 in pregnancy induced hypertension and 248 mmol/l in control for
      uric acid). CONCLUSION: The risk of development of chronic hypertension 10 years
      after pregnancy complicated by pre-eclampsia and pregnancy induced hypertension
      is increased and this is closely related to residual renal disorder.

PMID- 11533781
TI  - In-patient treatment for resistant obsessive-compulsive disorder.
AB  - Obsessive Compulsive Disorder is one of the increasing psychological disorders.
      If not detected early and treated properly, obsessive-compulsive disorder usually
      becomes an incapacitating illness adversely affecting almost all aspects of the
      patient's life. Outpatient behavioral and pharmacotherapies frequently fail. This
      is a report on a severe case of obsessive-compulsive disorder that was treated as
      an in-patient with both behavior and pharmacotherapies, she was then followed up
      for 5 years with no relapse. The case reflects the importance and the need for in
      patient units for severe resistant obsessive compulsive cases especially in Saudi
      Arabia where we have an increasing number of such cases.

PMID- 11533782
TI  - Intracranial tuberculoma.
AB  - Six patients with cerebral tuberculoma seen over a 2 year period are reported.
      Their clinical presentations, the result of investigations including radiological
      findings and their response to medical treatment are discussed and correlated
      with other reports in the literature. Eighty five percent of the patients were
      above the age of 30 years. All patients had negative past history of tuberculosis
      and both chest x-ray and erythrocyte sedimentation rate were within normal
      limits. Five patients presented with symptoms and signs of space occupying
      lesions but none had papilloedema. Two patients showed paradoxical enlargement or
      development of new tuberculous lesions during antituberculous therapy. The
      diagnosis was established by brain magnetic resonance imaging in 3 patients, and
      was further confirmed by brain biopsy in the other 3. All patients received
      antituberculous treatment for 12 months, except one who continued medication for
      2 years. Four patients normalized with medical treatment. Intracranial
      tuberculoma must be included in the differential diagnosis of a space occupying
      lesion. Magnetic resonance imaging is a sensitive, non-invasive method to
      diagnose cerebral tuberculoma. Paradoxical enlargement or development of new
      tuberculomas during antituberculous therapy is a documented phenomenon which can
      be overcome by continuation of antituberculous treatment. Twelve months of
      antituberculous treatment is considered to be adequate to resolve intracranial
      tuberculoma.

PMID- 11533783
TI  - An unusual case of impacted esophageal foreign body.
AB  - Incidental ingestion of foreign bodies in the pediatric age group is a recognized
      problem worldwide, however, it is unusual to have a neonate who presents with
      impacted esophageal foreign body. As such, this case is rare and considered a new
      form of child neglect.

PMID- 11533784
TI  - Traumatic rupture of corpus cavernosum.
AB  - Traumatic rupture of corpora cavernosa is an uncommon injury. We report a case of
      fractured penis in a 60 year old which was managed by immediate exploration and
      operative repair. Post operative recovery was uneventful with full return of
      erectile function.

PMID- 11533785
TI  - Evolution of resuscitation: a historical perspective.

PMID- 11533786
TI  - Congenital chloride diarrhea from the west coast of the Kingdom of Saudi Arabia.

PMID- 11533787
TI  - Unnecessary x-rays: occurrence, disadvantages and side effects.

PMID- 11533788
TI  - Neonatal septicemia.

PMID- 11533789
TI  - A guideline to clinical utility of prostate specific antigen.
AB  - Prostate cancer has emerged as the most common tumor effecting adult men. In the
      USA, 300,000 cases each year, and some 40,000 deaths per year are expected from
      this disease. Once prostate cancer gets to an advanced stage, one cannot prevent
      its progression and cure is no longer possible. Thus, to effect the course of
      prostate cancer and to diminish the death rate from this disease, it should be
      detected at its early stages. The prostate specific antigen serum test is the
      best tumor marker present but it is certainly not perfect. The proper utility of
      prostate specific antigen testing, and analysis of prostate specific antigen
      parameters, will allow us to detect prostate cancer at earlier stages, and
      prevent progression and death rates from this disease. In this manuscript, we
      review the current status of prostate specific antigen testing for early
      detection and staging of prostate cancer, as well as its role for monitoring
      response to various forms of therapy.

PMID- 11533790
TI  - Cardiac markers for assessing the acute coronary syndromes. A focus on cardiac
      troponins.
AB  - Markers of myocardial injury will continue to play an essential role in the
      assessment and management of patients presenting within the spectrum of acute
      coronary syndromes, a term representing the continuum of acute myocardial
      ischemia ranging from angina through Q-wave myocardial infarction. Coronary
      artery lesion instability can be detected by markers of plaque inflammation and
      disruption, platelets reactivity, and thrombosis. When myocardial injury occurs
      with severe impairment of coronary blood flow, several markers are released from
      the damaged myocyte. For many years, creatine kinase-MB isoenzyme has been the
      conventional marker for myocardial infarction. Despite its inadequate sensitivity
      and specificity for myocardial injury, creatine kinase-MB remains an essential
      component in assessing re-infarction or infarct extension, as well as in
      monitoring reperfusion after thrombolytic therapy when combined with myoglobin.
      Among the many cardiac markers for myocardial necrosis, cardiac troponins possess
      superior sensitivity and specificity for the detection of myocardial injury. In
      addition to their superior performance in detecting minor myocardial damage,
      cardiac troponins can be useful in detecting perioperative myocardial infarction,
      infarct size, improving risk stratification, and facilitating therapeutic
      decision making in patients with acute coronary syndromes.

PMID- 11533791
TI  - Cardio-respiratory responses to moderately heavy aerobic exercise during the
      Ramadan fasts.
AB  - OBJECTIVE: The aim of this study was to quantify the magnitude of the
      cardiovascular and respiratory changes that occur during the month of Ramadan in
      response to moderately heavy aerobic physical exertion. METHODS: Eighteen
      sedentary Kuwaiti adult males were tested under thermo-neutral conditions during
      a spring-like month of Ramadan and one month thereafter. RESULTS: There were no
      significant changes in maximal exercise capacity, treadmill walking efficiency,
      percentage VO2 max, in body weight and composition associated with Ramadan
      fasting or one month after. Cardiac (heart rate) and ventilatory responses to
      moderately intense bouts of sub-maximal aerobic exercise (70% of VO2 max) were
      actually slightly (<5%) but significantly (P<0.05) reduced, while exercise
      systolic but not diastolic pressure increased slightly (6%) by the end of
      Ramadan. CONCLUSION: Hormonal changes associated with dehydration or fasting,
      abstention from consumption of substances with negative inotropy and changes in
      circadian rhythms during Ramadan may be responsible for these mild changes in
      cardiorespiratory responses to exercise. Such changes had no negative effect on
      the physical aerobic performance of these subjects while exercising at moderately
      heavy intensity under thermally neutral conditions, during the month of Ramadan.
      Reduced ventilation during exercise may reflect a limited glycolytic capacity by
      the end of Ramadan.

PMID- 11533792
TI  - Healthcare risk waste in Saudi Arabia. Rate of generation.
AB  - OBJECTIVE: To assess the amount of healthcare risk waste generated by health
      establishments in Saudi Arabia METHODS: A healthcare waste management
      questionnaire was applied in 27 hospitals, and 16 primary health centres and
      clinics. The total quantity of healthcare risk waste collected in 24 hours in
      each of these establishments was weighed. Calculations were carried out to get
      hospitals rate of healthcare risk waste generation and primary healthcare centres
      risk waste generation. The total national estimate of healthcare risk waste
      production in kilograms/year for the whole health establishments in the Kingdom
      was then calculated. RESULTS: The mean hospital healthcare risk waste rate of
      generation was 1.13+/-0.96 kg/bed/day. The mean primary healthcare centres and
      clinics healthcare risk waste rate of generation was 0.08+/-0.08 kg/visitor/day.
      The estimated mean amount of all healthcare risk waste generated in the Kingdom
      of Saudi Arabia is 25,207 tons/year. CONCLUSION: Healthcare establishments in
      Saudi Arabia produce healthcare risk waste. Much care is given by the responsible
      authorities for the management of that type of waste. A program is being
      established to formulate standards for healthcare waste management

PMID- 11533793
TI  - Acoustic reflex threshold and loudness discomfort.
AB  - OBJECTIVE: Trying to find an accurate relation between loudness discomfort level
      and acoustic reflex threshold. METHODS: Seventy patients were involved in this
      study. Ten normal patients, 30 patients of unilateral conductive hearing loss and
      30 patients of unilateral or bilateral, mild to moderate sensorineural hearing
      loss were tested by 1, 2, KH2 pure tones, 0.5, 1, 2, 4, 8 KHz narrow band noise,
      wide band noise and speech noise stimuli to get loudness discomfort level and
      acoustic reflex threshold in each ear for each stimulus. RESULTS: Ninety two
      percent of predicted loudness discomfort levels occurred within +/-6 of acoustic
      reflex threshold rescaled data, when least squares regression method was applied.
      CONCLUSION: It is apparent that predicted results are statically significant.
      They are not constant value, but vary according to the acoustic reflex threshold
      change, stimulus used and hearing situation (normal, conductive or perceptive
      loss).

PMID- 11533795
TI  - Management strategies for peripheral tuberculous lymphadenopathy.
AB  - OBJECTIVE: To assess the usual means for diagnosing peripheral tuberculous
      lymphadenitis and present our experience in the management of the disease.
      METHODS: Three hundred and two patients with peripheral lymphadenopathy due to
      tuberculosis were diagnosed and referred by several hospitals in 9 governorates
      to the National Tuberculosis Institute. Patients were reviewed prospectively
      regarding diagnosis and treatment. RESULTS: Histological findings were diagnostic
      in 94% of patients. In our experience, isolation of mycobacterium from the lymph
      node tissue was neither practical nor reliable. Four out of 54 patients with
      bulky caseating nodes or discharging sinuses failed to respond to chemotherapy
      after 2 months of treatment. CONCLUSION: Histopathological diagnosis was the most
      practical method for diagnosing peripheral tuberculous lymphadenopathy. We
      recommend that patients who had bulky caseating nodes or discharging sinuses, to
      undergo surgical excision followed by chemotherapy.

PMID- 11533794
TI  - Ketotifen in treatment of uncomplicated falciparum malaria.
AB  - OBJECTIVE: The present in vivo study evaluates the potential use of ketotifen, a
      tricyclic antihistaminic drug, in treatment of Sudanese patients with
      uncomplicated Plasmodium falciparum malaria (19-38 years). METHODS: Four groups
      of patients (each has 15) were randomly selected and treated by chloroquine
      (25mg/kg wt) in comparison with regimen combinations of ketotifen (0.13 mg/kg
      body wt) with chloroquine, ketotifen with Fansidar (33.3mg/kg body wt) and
      ketotifen with both chloroquine and Fansidar. RESULTS: Prior to treatment all
      patients had a parasite density that varied from 1 x 10(3)-3.46 x 10(4)/mL blood.
      On day 2, the highest level of parasitaemia was recorded in patients treated with
      chloroquine only. Other patients had a significantly lower parasitaemia (P<0.05)
      with an average range of 111-243 parasites/300 leucocytes. On day 3 no parasites
      were detected in groups treated by ketotifen and Fansidar or by ketotifen in
      combination with Fansidar and chloroquine. The mean time of parasite clearance
      was minimum (<32 h) amongst patients that had chloroquine administered with
      ketotifen alone or with both Fansidar and ketotifen. The cumulative percentage of
      cases with recrudescence was >39% in groups that had the chloroquine regimen
      alone or the combination of chloroquine with ketotifen. A single case of
      recrudescence was also diagnosed on day 28 in the group treated with ketotifen
      plus fansidar but no recrudescence occurred in the group treated with the
      combination of the three drugs. CONCLUSION: This study indicates the possible
      role of ketotifen in treatment for falciparum malaria particularly when
      administered in combination with chloroquine and fansidar.

PMID- 11533796
TI  - Hospital morbidity due to post-operative infections in obstetrics & gynecology.
AB  - OBJECTIVE: To study the incidence and risk factors for postoperative infection
      following cesarean sections and major gynecological surgery. METHODS:
      Postoperative infection was documented in the specified registers in all patients
      following cesarean sections and major gynecological surgery from January 1997 to
      December 1998. This study was a part of the prospective analysis of hospital
      based morbidity and mortality in the Department of Obstetrics and Gynecology.
      RESULTS: There were a total of 89 cases of postoperative infections amongst 4,032
      patients undergoing major operations giving an overall infection rate of 2.2%.
      The morbidity due to infections was 3.3% in cesarean sections and 0.9% in major
      gynecological surgery. Abdominal hysterectomies had a higher infection rate than
      vaginal surgery. The most common causative organisms isolated were Enterococcus,
      Staphylococcus and Klebsiella species. CONCLUSION: It was found that vaginal
      flora was a significant source of contamination during surgery, which could be
      minimised by local sterilisation methods. The high infective morbidity in
      abdominal hysterectomies needs further analysis of the risk factors. Infection
      surveillance with a regular review of antibiotic protocols is recommended.

PMID- 11533797
TI  - The use of indomethacin for the prevention of intraventricular brain hemorrhage
      in high-risk neonates.
AB  - OBJECTIVE: The objective of this study was to determine the effect of
      indomethacin on reducing the incidence of intraventricular hemorrhage in
      premature infants treated in our units at King Faisal Specialist Hospital and
      Research Centre. METHODS: This historical cohort study included 45 infants born
      with birth weights of 1250 g or less and received indomethacin in the first 12
      hours of life for intraventricular hemorrhage prevention. The treated infants
      were compared to 33 other infants with birth weights of 1250 g or less who did
      not receive indomethacin for intraventricular hemorrhage prevention. Data
      collected included demographic, complications of prematurity, renal function and
      maternal data. RESULTS: Mean birth weight (grams) and gestational age (week) were
      928.6+/-34, 1066.2+/-38.9, 27.2+/-0.37 and 29+/-0.42 for the treated and the
      control infants. Overall incidence of intraventricular hemorrhage decreased
      significantly in the treated infants in comparison to the controls (P=0.0169).
      There was no infant with Grade 3-4 intraventricular hemorrhage found in the
      treated group while 2 developed grade 3-4 intraventricular in the control group
      which was insignificant. There were no statistically significant differences
      between the groups in terms of the complications of prematurity, Apgar scores at
      5 minutes, airleak syndrome and the use of umbilical catheters. The total fluid
      intake in the first 4 days after starting the treatment was comparable between
      the groups. There were no significant differences between the groups in urine
      output in day 1, 3 and 4. However the urine output decreased significantly in day
      2 in the treated group (P = 0.0349). There were no statistically significant
      differences in serum urea and creatinine between the groups. CONCLUSION: Low dose
      indomethacin given in the first 12 hours of life was shown to be associated with
      a decrease in intraventricular hemorrhage in premature infants and it was not
      associated with significant adverse effect.

PMID- 11533798
TI  - Somatostatin damage on the pancreatic islets.
AB  - OBJECTIVE: To study the histological appearance of the pancreatic islets
      consequent to prolonged regular daily treatment with somatostatin. METHODS:
      Thirty albino rats of each sex were divided into controls and another 2 groups;
      the first received the hormone somatostatin for 21 days and the second for 42
      days. Pancreatic specimens were taken from the sacrificed animals by the end of
      these periods. Examination by light microscopy of these specimens was carried
      out. Insulin and glucose were regularly measured through out the course of
      treatment. RESULTS: Showed irreversible damage of the alpha and beta cells of the
      islets. All animals developed gradually and continuously deteriorating diabetes
      mellitus. All the animals perished within a few days after cessation of
      treatment. CONCLUSION: A relatively long term treatment with somatostatin had an
      everlasting killing effect on both of the pancreatic islets and the animals
      themselves. A recommendation has been put forward to seriously requestion the
      clinical therapy of this hormone.

PMID- 11533799
TI  - The characteristics of systemic lupus erythematosus. A study in a general
      hospital.
AB  - OBJECTIVE: There is a wide variation in the natural history of Systemic Lupus
      Erythematosus among different ethnic and geographical groups. Studies in Arabs
      are few. This study aims to demonstrate the clinical characteristics of Systemic
      Lupus Erythematosus patients in Jordanians. METHODS: A retrospective review of
      the records of the cases diagnosed as Systemic Lupus Erythematosus in a tertiary
      referral centre (King Hussein Medical Centre) over the years 1991-1997. The
      records were analyzed for age, sex, presentation, diagnostic criteria,
      investigations, complications and treatment. RESULTS: Seventy-six records were
      analyzed. The patients were from all parts of Jordan, with a mean age of 20
      years. The female: male ratio was 24:1. The presentation was arthralgia-arthritis
      in 68 (89%) patients; skin manifestations in the form of malar rash in 32 (42%),
      photosensitivity in 19 (25%). Central nervous system manifestations were also
      noted in 21 (27%) of the patients. Anti-nuclear antibodies were positive in 71
      (93%) patients, anti double stranded DNA (DsDNA) positive in 80%. Anemia and
      leukopenia or both were noted in 52 patients(69%). Erythrocyte Sedimentation Rate
      was more than 30mm in the first hour in 49 (88%) patients. Lupus anticoagulants
      were negative in 75% of patients, renal impairment was documented in 46% of the
      patients (35 patients) with positive correlation to DsDNA. All the patients
      received steroids, 95% (73) in the form of prednisolone and 5% in the form of
      methylprednisolone; cytotoxics either cyclophosphamide or azathioprine mainly for
      renal disease were prescribed to 25 patients, Complications were hypertension (18
      patients), renal failure (7 patients), cerebral vascular disease (3 patients).
      Death was recorded in 3 subjects within 1-4 years of diagnosis CONCLUSION: This
      study demonstrates the presentations of Systemic Lupus Erythematosus patients
      with a high incidence of complications, which may be due to late presentation or
      late diagnosis. Further studies are needed on the natural history of this disease
      in Jordanians.

PMID- 11533800
TI  - Invasive mucormycosis in benign gastric ulcer.
AB  - Fungal elements are frequently noted overlying the base of chronic peptic ulcers
      of the stomach and it has been suggested that the fungi enhance the degree of
      necrosis and that these cases have protracted disease and deeper ulcers with more
      perforations. It has also been postulated that the number of fungal elements
      might be increased in the stomach of patients who are receiving potent
      medications such as H2-receptor antagonists to reduce gastric acidity, but there
      have not been adequate control studies, and the deleterious effects from the
      presence of the fungi in these cases have not been substantiated. We present a
      very rare case of invasive mucormycosis (phycomycosis) occurring in the base of a
      chronic gastric ulcer in a 55 years old diabetic male. This case was clinically
      and radiologically been mistaken for a gastric carcinoma. In addition, the ulcer
      was complicated by perforation and fungal septicemia with subsequent fatal
      outcome. The clinical, radiological and histopathological features are described
      together with a literature review of other reported fungal gastric ulcers.

PMID- 11533801
TI  - Malignant peritoneal mesothelioma.
AB  - Malignant peritoneal mesotheliomas are rare tumors arising from the peritoneal
      surface. We report a 53 year old, non-asbestos exposed Saudi male who presented
      with exudative ascites. The diagnosis was obtained from laparoscopic biopsy. To
      the best of our knowledge this entity has not been described in the Saudi
      community. The aim is to increase the awareness among the medical community about
      this rare entity.

PMID- 11533802
TI  - Quadruplet pregnancy following a single course of clomiphene citrate. An
      expensive success.
AB  - Prescribing clomiphene citrate for infertility patients has been taken very
      lightly. High order pregnancy can happen with this treatment. In addition to high
      perinatal mortality and morbidity of multiple pregnancy, the economic and social
      strains on the national health system and the family is great. The case presented
      showed that although the outcome of pregnancy was successful but the cost to the
      national health was tremendous. It is therefore recommended that measures should
      be taken to avoid high order births. Moreover, delaying the delivery, if
      possible, will be cost effective.

PMID- 11533803
TI  - Arthrogryposis, renal dysfunction and cholestasis syndrome.
AB  - We report for the first time from the Arabian Gulf area 3 patients with
      arthrogryposis multiplex congenita, cholestasis and renal tubular dysfunction
      from a Saudi family with 2 other siblings and 3 cousins who possibly died with a
      similar clinical picture. We also document for the second time in literature
      other findings in this syndrome including cerebral abnormalities (hypoplastic
      corpus callosum), congenital heart disease and nerve deafness. We suggest that
      some of these cases might benefit from ursodeoxycholic acid therapy. We believe
      that this autosomal recessive disorder is possibly under-diagnosed in this region
      with a high consanguineous marriage rate.

PMID- 11533804
TI  - Squamous cell carcinoma complicating prurigo nodularis.
AB  - Squamous cell carcinoma complicating ulcerative prurigo nodularis is described in
      2 patients who were having prurigo nodularis on dorsum of the feet for duration
      of many years. Biopsy specimens from the ulcerating nodules showed features of
      squamous cell carcinoma. This finding has not been previously reported. Squamous
      cell carcinoma should be considered in the evaluation of long standing ulcerative
      lesion of prurigo nodularis especially when not responding to conventional
      therapy.

PMID- 11533805
TI  - Agenesis of right lung with esophageal atresia and distal tracheoesophageal
      fistula.

PMID- 11533806
TI  - Admission patterns and outcomes of sick children: experience from a pediatric
      intensive care unit in Oman.

PMID- 11533807
TI  - The midstream muddle.

PMID- 11533808
TI  - Histiocytosis X and Caroli's disease.

PMID- 11533809
TI  - A need for managed care in Saudi Arabia.
AB  - Is the Kingdom of Saudi Arabia getting value for money invested in health?
      Quality care is being provided throughout health facilities in the Kingdom,
      however there is minimal control of utilization in all health sectors,
      consequently leading to abuse and over utilization, particularly in the public
      sector. Managed care programs have proven effective in reducing unnecessary
      inpatient and ancillary service utilization by reducing use of expensive
      procedures and unnecessary, highly specialized services, and shifting to less
      expensive care options. Health maintenance organizations are the best example of
      a managed health care model; tracking good performance and cost savings averaging
      between 20-40% compared to more traditional health plans. Key features of health
      maintenance organizations include serving a defined population voluntarily
      enrolled in the health plan; assumption of contractual responsibility and
      financial risk by plan to provide a range of services, and payment of a fixed
      periodic payment by the enrollee, independent of the actual use of services. The
      key characteristic that distinguishes health maintenance organizations from other
      delivery systems is prepayment for the care that is provided. Preferred Provider
      Organizations offer discounts for services received from a selected set of
      physicians and hospitals. Services received by enrollees are not fully reimbursed
      from this selected list of providers. Preferred Provider Organizations use health
      maintenance organizations administrative processes for controlling costs but do
      not include some of the intrinsic cost and quality controls of health maintenance
      organizations. Review of several studies indicate that patients enrolled in
      prepaid group practices (managed care organizations) were hospitalized 15-40%
      less often than those enrolled in fee-for-service health plans.

PMID- 11533810
TI  - Undergraduate curriculum reform in Saudi medical schools. Which direction to go?
AB  - Curriculum reform in undergraduate medical education is quite essential for the
      success of the educational process. Saudi medical schools have been involved in
      curriculum reform over the past 2 decades. Review of the existing literature
      identifies the following as problems with today's curriculum including:
      Overcrowding of the curriculum, over presentation of some subjects, presence of
      relatively non-relevant subjects, dissociation between basic and clinical
      sciences, repetition of lectures and exams, need for new subjects of clinical
      relevance, predominantly hospital based medical education with minimal community
      based practice, as well as non-optimal use of resources. The authors put forth
      suggestions for reform of the current curriculum to meet today's problems and
      future demands.

PMID- 11533811
TI  - Where is critical care medicine in today's undergraduate medical curriculum?
AB  - Critical Care Medicine is a well-established specialty in developed countries.
      Medical students have exposure to it at undergraduate level and it is an
      independent subspecialty at postgraduate level. However, in the Kingdom of Saudi
      Arabia, Critical Care Medicine is minimally taught under other subject headings
      in Surgery, Internal Medicine or Anesthesia. This article discusses the need for
      the inclusion of Critical Care Medicine in the undergraduate curriculum for
      better integration of basic and clinical sciences on one hand and improvement of
      the student's base of knowledge and quality of patient care on the other.

PMID- 11533812
TI  - Ectopic pregnancy in Abha, Saudi Arabia. A continuing conundrum.
AB  - OBJECTIVE: To determine the incidence of ectopic pregnancy in Abha, in the south
      western region of Saudi Arabia and to evaluate the relevance of the known risk
      factors. METHODS: Eighty-two women with histologically confirmed ectopic
      pregnancies, managed in Abha Maternity Hospital over a three-and-a-half year
      period, were retrospectively studied. RESULTS: The incidence of ectopic pregnancy
      was 0.74 per 100 live births. Most (56%) of our patients were within the 21-30
      age group. Parous women constituted 56% and nulliparous patients constituted 21%
      of the study group. No previous history of abortion was found in 60% of the
      patients. Fourteen (17%) had used the intra uterine contraceptive device and 5%
      had a history of previous ectopic pregnancy. There were 3 cases of heterotopic
      pregnancies in the series. The right and left fallopian tubes were equally
      affected. Salpingectomy (90%) was the most frequent definitive surgical procedure
      performed, and 15% of the patients required blood transfusion. There was no
      obvious seasonal variation and no maternal death was reported. CONCLUSION: The
      incidence of ectopic pregnancy appears to be comparatively low in our community
      and the risk factors do not seem to be clearly defined. A nation-wide multicenter
      survey to determine the effect of climatic factors and to check, as routine,
      Chlamydia trachomatis serology in suspected cases of ectopic pregnancy, may be
      desirable. Without these determinations, ectopic pregnancy and possible
      preventive measures may continue to remain a conundrum.

PMID- 11533813
TI  - A simplified management of diabetic pregnant woman.
AB  - OBJECTIVE: To evaluate a simplified management of diabetic pregnant women.
      METHODS: A prospective study of the management of all diabetic pregnant women
      (74) during 2 years from March 1995-March 1997 was carried out in the Department
      of Obstetrics & Gynecology, Wad Medani Teaching Hospital, Sudan. Diabetes was
      diagnosed by an oral glucose tolerance test according to the World Health
      Organization criteria. Patients were controlled by insulin and monitored by urine
      for glucose and pre-prandial blood sugar. They were delivered by induction of
      labor or cesarean section at 38 weeks. Basic resuscitation was carried out for
      all babies. Intravenous glucose was given to babies when hypoglycemia was
      diagnosed. Early breast feeding was the rule. Babies who developed complications
      were managed at the special care unit in the Children's Hospital. RESULTS:
      Seventy one patients completed the management, 2 ended in abortion and 69
      proceeded to 30 weeks or more. There was one maternal death and 14 perinatal
      deaths. The main causes of perinatal deaths--Wigglesworth classification--were
      macerated stillbirth (5), congenital malformation (4) and intrapartum asphyxia
      (5). A reasonable control of diabetes (pre-prandial 179 or less) was achieved in
      56 patients (79%). Seventy percent of the patients were delivered by cesarean
      section and the main indications were big baby (16 cases) and a previous cesarean
      section (20 cases). Fifty four percent of all the patients had a history of
      perinatal death, 28% had a history of repeated abortions and there was a definite
      family history of diabetes in 53%. Sixty nine percent of the patients were at the
      age 30 years or more and 50% of them were of the parity 5 or more. CONCLUSION:
      This simplified management of diabetic pregnant women is satisfactory and
      feasible under our present circumstances. It is hoped that improvement in ante
      natal care, delivery care and control of diabetes around the time of conception
      and care of the newborn will reduce the perinatal mortality rate.

PMID- 11533814
TI  - The prevalence of overweight and obesity amongst hypertensive and diabetic adult
      patients in primary health care.
AB  - OBJECTIVE: To estimate the prevalence of overweight and obesity amongst
      hypertensive and diabetic adult patients in primary health care centers, Riyadh,
      Saudi Arabia. METHODS: A retrospective review of the medical records of 3186
      adult hypertensive and diabetic patients in 10 primary health care centers in
      Riyadh, from August to October 1999. RESULTS: Nineteen percent of the patients
      were their ideal weight (body mass index < 25 kg/m2), while 35% were overweight
      (body mass index 25-29.9 kg/m2). Forty one percent were moderately obese (body
      mass index 30-40 kg/m2) and 5% were morbidly obese (body mass index > 40 kg/m2).
      CONCLUSION: Overweight and obesity are coexisting risk factors amongst
      hypertensive and diabetic adult patients, and are an important focus for
      treatment and prevention of high blood pressure and diabetes.

PMID- 11533815
TI  - Bacteriology of diabetic foot.
AB  - OBJECTIVES: To study the relative frequency of bacterial isolates cultured from
      diabetic foot infections and assess their comparative in vitro susceptibility to
      the commonly used antibacterial agents. METHODS: This is a retrospective study
      with a review of the bacteriology results of specimens taken from 111 consecutive
      patients with diabetic foot infections at King Abdulaziz University Hospital,
      Jeddah, Kingdom of Saudi Arabia, during the period January 1997 to June 1999. The
      specimens were cultured using optimal aerobic and anaerobic microbiologic
      techniques. Antimicrobial susceptibility testing to different agents, was carried
      out using the disc diffusion method. RESULTS: Staphylococcus aureus was the
      commonest isolate being recovered from 28% of cases, including methicillin
      resistant staphylococcus aureus in 9 of 30 (30%) patient wounds. The other
      organisms isolated were Pseudomonas aeruginosa (22%) and Proteus mirabilis (18%),
      anaerobic gram-negative organisms (11%) mainly Bacteroides fragilis. The
      antimicrobial susceptibility testing, showed that vancomycin was the most
      effective against gram-positive and and imipenem was the most effective against
      gram-negative organisms. CONCLUSION: Staphylococcus aureus, Pseudomonas
      aeruginosa, Proteus mirabilis and Bacteroides fragilis were the most common
      causes of diabetic foot infections. These wounds require use of combined
      antimicrobial therapy for initial patient management prior to susceptibility
      results.

PMID- 11533816
TI  - Efficacy and acceptability of depo-medroxyprogesterone acetate injection. As a
      method of contraception in Saudi Arabia.
AB  - OBJECTIVE: To determine the efficacy and acceptability of Depo
      Medroxyprogesterone acetate (depo-provera) among the women using that method of
      contraception at King Faisal Military Hospital in the south-west region of Saudi
      Arabia. METHODS: A preliminary retrospective and questionnaire analysis of 165
      Saudi women who had depo-provera as a method of contraception at the
      contraception clinic of King Faisal Military Hospital over a period of 2 months.
      RESULTS: The mean age of the women was 31.21 years and the mean parity 6.77.
      There was no pregnancy reported during the period of use of the contraceptive
      method which ranged from 3 months to 7.25 years. The side effects were mainly
      irregular spotting (69%), continuous bleeding per vaginam (7%), amenorrhoea (8%)
      and menorrhagia (1%). The rest reported normal menstrual pattern. Irregular
      spotting was common in women who had used the method for less than 2 years while
      amenorrhoea was the most common menstrual abnormality after 3 years of use. The
      other complaints included weight gain, loss of hair, abdominal pain and backache.
      The side effects were not acceptable to 4% of the women and they tried other
      methods of contraception. Thirteen percent of the women became pregnant after
      stopping the injections within intervals varying between 6 months to 2 years.
      Seventeen percent were using the method for the 2nd time. CONCLUSION: Depo
      provera is a very effective form of contraception in our community. While a few
      of the patients (4%) in our series would try other methods if not happy with the
      side effects, the majority were prepared to cope with the side effects as long as
      the desired prevention of pregnancy was guaranteed. Further studies are needed to
      validate these findings.

PMID- 11533817
TI  - Etiology and outcome of thyrotoxicosis at a university hospital.
AB  - OBJECTIVE: To determine the causes, clinical manifestations, mode of treatment,
      and outcome of hyperthyroidism at King Abdulaziz University Hospital. METHODS: A
      retrospective study of all cases of thyrotoxicosis diagnosed at King Abdulaziz
      University Hospital, Jeddah, Kingdom of Saudi Arabia, in the period between
      January 1997 to January 1999, that received a minimum of one year treatment.
      RESULTS: A total of 203 patients were seen with female: male ratio of 3.8:1 and
      mean age of 35.49+/-10.86 years. Graves' disease was the underlying cause in 69%
      of cases, toxic multi nodular goiter in 29%, and toxic adenoma and sub acute
      thyroiditis in 1% each. Palpitations, tremor, weight loss and nervousness were
      the commonest presenting manifestations. Forty-five (45%) of patients were
      treated with antithyroid drugs, 36% with radioactive iodine and 18% underwent
      subtotal thyroidectomy. Post radiotherapy hypothyroidism developed in 37% of
      patients. CONCLUSION: Causes and clinical manifestations of thyrotoxicosis in our
      patients were comparable with those reported in the literature. There is under
      use of radioactive iodine therapy, and physicians should be encouraged to use
      this mode of therapy as its efficacy, safety and low cost made it the preferred
      definitive treatment in most patients with hyperthyroidism.

PMID- 11533818
TI  - Frequency of herpes simplex virus in Syria based on type-specific serological
      assay.
AB  - OBJECTIVE: This study aimed to determine the seroprevalence of herpes simplex
      virus types 1 and 2 antibodies in Syrian populations. Serum samples collected
      between 1995-1998 from a total of 1293 healthy persons, neonates, pregnant women,
      labial herpes patients, kidney transplantation patients, atherosclerosis
      patients, cervical cancer patients, patients with suspected herpetic keratitis,
      viral encephalitis patients, patients with sexually transmitted diseases, AIDS
      patients, female prostitutes and bar girls. METHODS: Serum samples were studied
      by enzyme immunosorbent assay using herpes simplex virus type-specific antigen,
      glycoprotein (gG). RESULTS: In the healthy group, herpes simplex virus type 1
      infections correlated mostly with age and was prevalent among subjects >30 years
      (approximately 95% of persons in our country have herpes simplex virus type 1
      antibodies by 30 years of age), while they varied moderately among other groups.
      Herpes simplex virus type 2 prevalence varied greatly among the groups defined by
      sexual activity and was associated with risk behavior for prostitution. Herpes
      simplex virus type 2 seroprevalence was highest among prostitutes (34%) and bar
      girls (20%); lowest in healthy persons (0.15%); and intermediate in sexually
      transmitted disease patients (9.5%), cervical cancer patients (8%) and AIDS
      patients (4%). CONCLUSION: It can be concluded that infection of herpes simplex
      virus type 2 is very rare in persons in our country.

PMID- 11533819
TI  - Complications of carbon monoxide poisoning.
AB  - OBJECTIVE: Acute carbon monoxide poisoning is a common problem that occurs during
      winter and leads to serious complications. METHODS: We retrospectively studied 24
      consecutive cases admitted with the aim of finding the causes and outcome of
      acute carbon monoxide poisoning. RESULTS: The source of poisoning was charcoal in
      71% of patients, motor gasoline in 21%, and other causes in 8%. Immediate
      complications included altered consciousness level in 54% of patients, metabolic
      acidosis in 46%, pneumonia in 42%, cardiac arrhythmia in 29% and rhabdomyolysis
      in 25%. Late neurological complications occurred in 17% of patients. All the
      patients received 100% oxygen. Eleven patients (46%) required mechanical
      ventilation. Ultimately, 19 patients (79%) recovered completely, 4 (17%) had
      neurological or cardiac disorders, and 1 (4%) died. CONCLUSION: Immediate and
      late complications are common in carbon monoxide poisoning cases admitted to the
      hospital especially when they arrive late. Time lapse between exposure and
      presentation may have a role in predicting the outcome.

PMID- 11533820
TI  - Anterior hypospadias. Is repair necessary with urination in a sitting or
      squatting position?
AB  - OBJECTIVE: To determine the chronic complication rate of anterior hypospadias
      repair and to explore whether the practice of placing the neomeatus at the tip of
      the penis should be applicable to all cases in our community where urination is
      in a sitting/squatting position. METHODS: Over a 10-year period commencing 1st
      September 1987, 312 patients had hypospadias repair of whom 72% had anterior
      hypospadias. The meatus was advanced to the tip of the penis in all repairs. The
      location of the meatus was also determined in 281 non-complaining men with a
      straight penis and normal sexual and reproductive functions. Following prior
      information that anterior hypospadias was not associated with sexual and
      reproductive dysfunction, 51 patients were given a choice between repair or no
      repair. RESULTS: Urethrocutaneous fistula occurred in 5% of patients, urethral
      stricture in 3% and meatal retraction in 3%, with 92% of patients having no
      complications. Forty six percent of non-complaining men had the meatus in
      locations other than the tip of the penis. Of 51 patients with the benefit of
      informed consent, 73% opted for no repair. CONCLUSION: Our results of anterior
      hypospadias repair compare favourably with those of other centers. Placement of
      the meatus at the tip of the penis for anterior hypospadias should not be
      applicable to all patients in this community where urination is in a
      sitting/squatting position. Before such repairs, an informed consent is warranted
      by making the patients and their parents aware of the non-association of sexual
      and reproductive disorders with these anomalies.

PMID- 11533821
TI  - Frequency of tracheobronchial foreign bodies in children and adolescents.
AB  - OBJECTIVE: The problem of foreign body aspiration in the community has been
      studied and compared with other reports. METHODS: We have retrospectively studied
      patients who had bronchoscopy for suspected foreign bodies in the
      tracheobronchial tree, attending or referred to Al-Noor Specialist Hospital,
      Makkah over a period of 3 years from May 1996 to May 1999. RESULTS: The total
      number of patients was 94 (62 male and 32 female). Ages ranged from 4 months to
      45 years(mean age 3.77 years), 85% of children being under the age of 5 years.
      One hundred bronchoscopies (6 repeat bronchoscopies) and one thoracotomy were
      carried out. Foreign bodies were removed from 60 patients (64%). Six (10%) did
      not have any definite history, while 15 patients (21%) with definite history of
      foreign body aspiration had negative bronchoscopy. An aspirated Fis-Fis (Alfalfa,
      Lucerne) seed accounted for more than one-third of all foreign bodies. The most
      frequent symptoms, signs, radiological findings and site of foreign body
      lodgement in the tracheobronchial tree are discussed. CONCLUSION: We conclude
      that a negative history, clinical examination and chest x-ray do not necessarily
      exclude aspirated foreign body material. Bronchoscopy is the most effective
      diagnostic and therapeutic modality to prevent complications related to neglected
      foreign body aspiration. In addition to children, teenagers and adolescents are
      also not immune to this problem. We recommend early referral to an appropriate
      hospital on suspicion or if symptoms persist. However, preventive measures,
      remain the best means of protecting these children.

PMID- 11533822
TI  - Pathological prognostic factors in breast carcinoma.
AB  - OBJECTIVE: Pathological prognostic factors in breast cancer are now widely used
      to predict biological behavior of cancer and to plan its effective management. In
      this paper, we attempt to evaluate the reports from our histopathology laboratory
      spanning over a period of 4 years, to assess completeness in recording these
      factors. It will enable us to improve and standardize reporting on breast cancer.
      METHODS: The pathology reports of primary carcinoma of the breast diagnosed in
      our laboratory from 1st January 1994 to 31st December 1997 (4 year period) were
      reviewed for details on tumor size, histological type and grade, presence or
      absence of tumor emboli in vascular channels, proximity of the tumor to resection
      margins and lymph node status. RESULTS: Tumor size was not recorded in 1 case
      each in 1994, 1995 and 1996 and 2 cases in 1997. Histological type was mentioned
      in all cases in 1995 and 1997. It was not mentioned in 1 case in 1994 and 3 cases
      in 1996. Out of 77 cases with axillary clearance, the total number of lymph nodes
      was recorded in 83% of cases. The number of lymph nodes with metastasis was
      recorded in 71% of cases. CONCLUSION: Our histopathology laboratory receives the
      majority of surgical biopsies carried out in the Sultanate of Oman. During our
      study period we received a total of 45354 biopsies. From 1993 onwards,
      pathological prognostic factors of breast carcinoma were incorporated in our
      pathology reports following the publication of major and leading articles
      regarding the same. This study shows an improvement in the quality of reports
      after introducing this concept in 1994. This study clearly reveals the necessity
      for written protocols to be established, to standardize and improve the quality
      of reporting.

PMID- 11533823
TI  - Utilization of primary health care during summer.
AB  - OBJECTIVES: To determine the workload on primary health care center services, to
      recognize the patterns of utilization of primary health care center services and
      morbidity patterns among the summer visitors who attended primary health care
      centers in Asir region in 1998. METHODS: A special form was designed to record
      demographic data, diagnosis and management. Ten percent of those forms were
      analyzed to study the patterns of morbidity and health service utilization. A
      special formula was used to calculate the size of the workload on the health
      services during the season. RESULTS: The total number of patients who attended
      primary health care centers during the study period was 387,727. Twenty-five
      percent of them were summer visitors. The workload on the health services
      increased by 33%. Both sexes utilized the services equally. Most of the visitors
      were young, Saudis, and utilized curative services. Respiratory related problems
      represented 60% and digestive related problems represented 12%. CONCLUSION: There
      was an excessive load on primary health care center services during the summer
      season. Re-organization, re-allocation of resources and provision of extra
      medical facilities in the Asir region are necessary to overcome this load.

PMID- 11533824
TI  - Penile metastasis from rectal carcinoma.
AB  - We are presenting a 65-year old patient with metastatic carcinoma of the penis
      which was discovered 19 months after abdomino-perineal resection for rectal
      cancer (Duke A). There was also metastasis in the perineum and one rib. Penile
      biopsy and cavernosography were carried out and established the metastatic
      nature. The patient declined further therapy and died 5 months after diagnosis.

PMID- 11533825
TI  - Post traumatic high-flow arterial priapism. The need for increased awareness
      among health care professionals.
AB  - High flow arterial priapism is a rare urological emergency. Presentation,
      diagnosis and institution of definitive management are often delayed. We describe
      our experience with this diagnostic entity and reviewed the literature to define
      possible reasons for the delayed diagnosis and management. We report two patients
      (10 years and 35 years old) that presented following blunt perineal trauma. The
      presentation and diagnosis of arterial priapism were delayed in both patients.
      Selective angiogram of the internal pudendal artery revealed arteriocavernous
      fistula in each patient. Embolization of the fistulae by gel foam was carried out
      at the same sitting. Penile detumescence was noted in both patients at the
      conclusion of the angiographic embolization. Both patients regained erectile
      function 3 and 6 weeks post treatment. Awareness of the various etiologic factors
      in priapism is of paramount importance to establish the correct diagnosis and
      institute the appropriate treatment modalities. Absence of pain and preservation
      of potency in patients with arterial priapism are among factors that contribute
      to the delayed presentation, diagnosis and treatment. We reiterate the valuable
      role for selective internal pudendal artery angiography as a single investigation
      that provides both diagnostic and therapeutic means of management.

PMID- 11533826
TI  - Widespread tuberculous calcification.
AB  - We are reporting an unusual case of widespread abdominal calcifications, in the
      peri-colic mesentery, liver and spleen. The diagnostic laparoscopy showed
      multiple encapsulated calcified hard rounded masses of varying size and shape,
      with marked adhesions in and around the bowel and mesentery. Histopathology
      identified them as calcified lymph nodes, but was unable to highlight the
      pathogenesis of these calcifications. The diagnosis of post tuberculous
      calcification of lymph nodes is made on the basis of exclusion. The subject was
      reviewed, to the best of our knowledge, there is no similar case, with such an
      extent of abdominal calcifications reported in the literature.

PMID- 11533827
TI  - Dandy-Walker syndrome in association with neurofibromatosis in monozygotic twins.
AB  - Dandy-Walker syndrome in monozygotic twins is reported. The twins reported,
      presented with delayed development, big head and dysmorphic features. In
      addition, there were significant cafe-au-lait spots on the trunk and other minor
      features consistent with the diagnosis of neurofibromatosis. To the best of our
      knowledge, Dandy-Walker syndrome in combination with neurofibromatosis in
      monozygotic twins has not been previously reported.

PMID- 11533828
TI  - Tumor-like presentation of multiple sclerosis.
AB  - Multiple sclerosis patients may present with clinical data suggestive of cerebral
      tumor, however, most of the lesions do not show expansive signs in computerized
      tomography of brain or magnetic resonance imaging. We report in this paper, 2
      patients who had shown expansive radiological signs suggestive of neoplasm.
      Cerebral biopsy was an important diagnostic procedure in these 2 cases which
      revealed the diagnosis of demyelinating disease.

PMID- 11533829
TI  - Acute right heart strain due to lung contusion.

PMID- 11533830
TI  - Multiple choice questions in Sudan medical schools: teachers views.

PMID- 11533831
TI  - Necrotizing fasciitis of abdominal wall after cesarean section.

PMID- 11533832
TI  - A clinico-dosimetric characteristic of radiotherapy in patients with early stages
      of breast cancer.

PMID- 11533833
TI  - Obesity among diabetic patients.

PMID- 11533834
TI  - Neonatal septicemia.

PMID- 11533836
TI  - To mask or not-to-mask.

PMID- 11533835
TI  - Pagets disease of the bone.

PMID- 11533837
TI  - The role of high-dose oral iron supplementation during erythropoietin therapy for
      anemia of prematurity.
AB  - OBJECTIVE: To assess whether a high intake of oral iron would increase the effect
      of recombinant human erythropoietin (rHuEPO) on hemoglobin synthesis. METHODS: We
      studied 30 preterm infants (gestational age 29+/-1.8 weeks, birth weight 1161+/
      200 g, at age of 28+/-10 days) who were randomly assigned to receive either 8
      mg/kg per day (n=15) or 16 mg/kg per day of oral iron during a course of rHuEPO
      therapy (900 microg/kg per week) for a duration of 4 weeks. Both groups were
      comparable in regard to clinical and laboratory data at the time of enrollment.
      RESULTS: rHuEPO caused a significant increase in reticulocyte count in the low-
      and high-dose iron groups, 17.1+/-5.3 to 34.7+/-9.2 and 16.3+/-3.3 to 42.5+/-5.6
      (10(9)/l), respectively (p<0.05). However, in both groups, hematocrit values
      remained stable at the end of the study as compared to baseline (0.35+/-0.03% vs.
      0.30+/-0.03%, 0.35+/-0.05% vs. 0.30+/-0.03%, NS) and in both groups there was a
      comparable and significant decrease in ferritin level (259+/-109 to 101+/-40 and
      168+/-54 to 69+/-38 microg/l, respectively; p<0.01). The rates of bloody stools
      without any evidence of necrotizing enterocolitis were not significantly
      different between the two treatment groups (1/15 vs. 4/15, NS). CONCLUSION: We
      conclude that a higher dose (16 mg/kg per day) of oral iron is not more
      beneficial when compared to a lower dose (8 mg/kg per day) during rHuEPO therapy
      for anemia of prematurity. Further studies will define the optimal dosage and
      route of administration of iron supplementation during rHuEPO therapy.

PMID- 11533838
TI  - Early high-frequency oscillatory ventilation versus synchronized intermittent
      mandatory ventilation in very low birth weight infants: a pilot study of two
      ventilation protocols.
AB  - OBJECTIVE: To evaluate the feasibility of conducting a prospective, randomized
      trial comparing early high-frequency oscillatory ventilation (HFOV) to
      synchronized intermittent mandatory ventilation (SIMV) in very low birth weight
      (VLBW) premature infants. This pilot study evaluated two ventilator management
      protocols to determine how well they could be implemented in a multicenter
      clinical trial. Although this pilot study was not powered to detect differences
      in outcome, we also collected outcome data. DESIGN: Prospective, multicenter,
      randomized pilot study. SETTING: Seven tertiary-level intensive care nurseries
      with previous experience with both HFOV and flow-triggered SIMV. PATIENTS: Fifty
      infants weighing 501 to 1200 g, less than 4 hours of age, who had received one
      dose of surfactant and required ventilation with mean airway pressure > or =6 cm
      H2O and F(I)O2 > or =0.25, and had an anticipated duration of ventilation greater
      than 24 hours. INTERVENTIONS: Patients were stratified by birth weight and
      prenatal steroid status, then randomized to either HFOV or SIMV with tidal volume
      monitoring. Ventilator management for patients in both study arms was strictly
      governed by protocols that included optimizing lung inflation and blood gases,
      weaning strategies, and extubation criteria. MEASUREMENTS: Data were collected
      using the tools planned for the larger collaborative study. Protocol compliance
      was closely monitored, with successive changes in the protocol made as necessary
      to improve clarity and increase compliance. The incidence of major neonatal
      adverse outcomes was recorded. MAIN RESULTS: Data are presented for 24 HFOV and
      24 SIMV infants (two infants, twins, were withdrawn from the study at parent's
      request). Nineteen of the 24 HFOV infants and 20 of the 24 SIMV infants survived
      to 36 weeks corrected age. Age at final extubation for survivors was 16+/-16
      (mean+/-SD) days for HFOV infants and 24+/-24 days for SIMV infants. At 36 weeks
      corrected age, 14 of the 19 HFOV survivors were extubated and in room air,
      whereas 5 required supplemental oxygen. In comparison, 6 of the 20 SIMV survivors
      were extubated and in room air, whereas 14 required supplemental oxygen. Grade
      III/IV IVH and/or periventricular leukomalacia occurred in 2 HFOV and 2 SIMV
      patients. Overall compliance with the ventilator protocols was 82% for the SIMV
      protocol, and 88% for the HFOV protocol. CONCLUSIONS: The preliminary outcome
      data supports conducting the large randomized trial, which began in July of 1998.
      The protocols for the ventilator management of VLBW infants, both with HFOV and
      with SIMV were easily implemented and consistently followed, and are presented
      here.

PMID- 11533839
TI  - Reducing light and sound in the neonatal intensive care unit: an evaluation of
      patient safety, staff satisfaction and costs.
AB  - OBJECTIVES: To modify an existing Level III neonatal intensive care unit and to
      compare light and sound levels in the renovated nursery with an adjacent
      traditionally configured nursery. Further, to assess the impact of this practice
      on patient safety, staff perceptions of the nursery environments, and to document
      costs of renovation. STUDY DESIGN: Prospective comparison of light and sound
      levels in identical six-bed patient rooms within an existing intensive care unit.
      One room was modified to reduce light and sound, and the other served as a
      control. Costs of renovation were documented. Patient characteristics, severity
      of illness and safety outcomes were documented following modifications. Physician
      and nursing staff were surveyed on their perceptions of the renovations. RESULTS:
      Both light and sound were reduced with modifications that incurred modest costs.
      Patient safety was not influenced adversely by reduced light or sound levels.
      Staff members were highly satisfied with reductions in sound levels. Reactions to
      reduced lighting levels were more mixed and led to modification of bedside
      lighting. CONCLUSIONS: Cost-effective renovations to an existing NICU are
      possible, desirable, and do not impact patient safety. The reductions achieved,
      however, are less than those reached with new construction.

PMID- 11533840
TI  - Transmission loss of sound into incubators: implications for voice perception by
      infants.
AB  - OBJECTIVE: To assess the transmission of sound into incubators as a function of
      talker position (i.e., standing or sitting), incubator port position (i.e.,
      opened or closed), and center frequency (i.e., 125 to 10,000 Hz in one-third
      octave steps). The second objective was to estimate the audibility of the human
      voice inside the incubator. STUDY DESIGN: L(eq) measures of signal transmission
      loss and motor noise were obtained from two incubators. RESULTS: In general,
      signal transmission loss was greater for the standing-talker position, with front
      portholes closed, and for high-frequency spectra. Motor noise was greater with
      both front portholes closed and for lower-frequency spectra. The greatest signal
      delivery to an infant would be obtained when the speaker is sitting using a
      raised vocal effort while the incubator ports are opened. CONCLUSION: Measured
      signal transmission loss and motor noise characteristics of two incubators
      suggest that only mid-frequency speech spectra would be audible to infants and
      only at a speech-to-noise ratio of approximately 5 to 10 dB with a raised vocal
      effort.

PMID- 11533841
TI  - Association of postnatal dexamethasone use and fungal sepsis in the development
      of severe retinopathy of prematurity and progression to laser therapy in
      extremely low-birth-weight infants.
AB  - OBJECTIVE: The objective of this study was to evaluate the role of postnatal
      dexamethasone use and fungal sepsis in the development of severe retinopathy and
      progression to laser therapy. BACKGROUND: Postnatal steroids have been frequently
      used in the management of infants with chronic lung disease, airway edema, and
      hypotension, but their use is not free from adverse effects. Postnatal
      dexamethasone use has been associated with increased risk for the development of
      fungal sepsis, but the influence of glucocorticoid therapy on retinopathy of
      prematurity (ROP) is controversial. Candida sepsis has been shown to be
      associated with severe ROP and the need for laser therapy in some studies but not
      in others. STUDY DESIGN: Medical records of all <1000 g birth weight infants
      (n=158) admitted to Louisiana State University Health Sciences Center between
      July 1, 1996 and June 30, 1999 were reviewed. After exclusion of those infants
      who either died (n=25) or transferred (n=3) before eye examination, demographic
      and clinical data of 130 infants were analyzed by chi-squared analysis, Mann
      Whitney U test, t-test, analysis of variance, and logistic regression. All data
      are mean+/-SD. RESULTS: Gestational age was 26.4+/-1.7 weeks; birth weight was
      797+/-130 g. Twenty-six infants were Caucasian, the rest African-American.
      Seventy-five (58%) received antenatal steroids. Eighty-eight (68%) of the infants
      received postnatal steroids. All infants were exclusively fed premature infant
      formulae. Sepsis developed in 44 (34%) infants and fungal sepsis in 14 (11%).
      Incidence of ROP was 77% (100/130), severe ROP (stage > or =3) 52% (68). Severe
      ROP was more frequent in Caucasian infants (p=0.005) and in infants who received
      postnatal dexamethasone (p< or =0.0001). The development of threshold ROP (zone 1
      or 2 with stage 3+, five contiguous or eight total clock hours of the retina) and
      requirement for laser therapy were higher in Caucasians (p=0.0002) and in infants
      with fungal sepsis (p=0.001). Antenatal steroids had no effect on the severity of
      ROP or the need for laser treatment. Postnatal dexamethasone use was
      significantly associated with fungal sepsis 13/14 (93%). After controlling for
      gestational age, race, days on supplemental oxygen, and fungal sepsis, cumulative
      postnatal dexamethasone use was independently associated with severe ROP [OR 1.2
      (1.04-1.33)], and fungal sepsis [OR 8.2 (2.0-33.0)] was independently associated
      with the need for laser therapy. CONCLUSIONS: Postnatal steroid use is an
      independent risk factor for development of severe ROP. The risk of threshold ROP
      requiring laser treatment was higher in infants who developed fungal sepsis.

PMID- 11533842
TI  - How can ethics be taught effectively?

PMID- 11533843
TI  - Donor human milk for preterm infants.
AB  - As survival rates for preterm infants improve, more attention is being focused on
      improving the quality of survival through optimal nutritional management. The
      benefits of human milk for term infants are well recognized, with current
      research suggesting that human milk may especially benefit the preterm infant.
      Some mothers are unable or unwilling to provide breastmilk for their infants.
      Although not as well studied as mother's own milk, pasteurized donor human milk
      can provide many of the components and benefits of human milk while eliminating
      the risk of transmission of infectious agents. Pasteurization does affect some of
      the nutritional and immunologic components of human milk, but many
      immunoglobulins, enzymes, hormones, and growth factors are unchanged or minimally
      decreased. In California donor human milk costs approximately $3.00 per ounce to
      purchase. A reduction in length of stay, necrotizing enterocolitis and sepsis may
      result in a relative saving of approximately $11 to the NICU or healthcare plan
      for each $1 spent for pasteurized donor milk.

PMID- 11533844
TI  - Prenatal transmission of dengue: two new cases.
AB  - Dengue is commonly observed in most tropical countries, but its transmission from
      mother to fetus has not been frequently described. We report two such cases. The
      first signs of dengue in the infants appeared on the 3rd and 9th days of life. In
      both, a bacterial infection was suspected initially. In areas where it is
      endemic, the diagnosis of dengue should be considered in the neonate with signs
      of bacterial infection. When dengue is suspected in a pregnant woman, laboratory
      investigation and extended observation of the newborn are advised.

PMID- 11533845
TI  - Lactobacillus acidophilus sepsis in a neonate.
AB  - Lactobacillus species are non-spore-forming, anaerobic, gram-positive rods that
      cause disease in immunocompromised adults. Few cases have been described in
      children. We present the case of a 2-month-old infant who apparently developed
      Lactobacillus acidophilus sepsis from an infected central venous catheter.
      Physicians should be aware that although Lactobacillus species rarely cause
      disease in children, they should be considered a possible pathogen when isolated
      from the blood of a newborn infant.

PMID- 11533846
TI  - Tocolytic magnesium sulfate toxicity and unexpected neonatal death.
AB  - A 31-year-old primigravida with twins had spontaneous rupture of the membranes at
      32 weeks' gestation. On admission, because of contractions, the mother was
      started on tocolytic magnesium sulfate (MgSO4) along with betamethasone and
      prophylactic antibiotics. About a day later, she was found to have magnesium
      toxicity. Her serum total magnesium level was 9.0 mg/dl. Tocolysis was
      immediately discontinued. At cesarean delivery the following day, twin A, a
      female, died at 30 minutes of age despite a vigorous resuscitation. Although the
      preceding fetal heart rate patterns had been reassuring and the umbilical blood
      gases were normal, quite unexpectedly, the Apgar scores were 1/1/0. An autopsy
      revealed no anatomic abnormalities. Twin B, a female who survived, was also
      intubated at delivery. During her stay in the Neonatal Intensive Care Unit, she
      was found to have modestly elevated levels of serum cardiotroponin T. In our
      opinion, it is probable that the death of twin A can be directly attributed to
      magnesium sulfate toxicity. Neonatologists who attend deliveries should be aware
      that unexpected death may occur in babies who were exposed to high doses of
      tocolytic MgSO4.

PMID- 11533848
TI  - Special imaging casebook. Dipygus or pygomelia.

PMID- 11533847
TI  - Special imaging casebook. Hypoplastic left heart, prostaglandin therapy gastric
      focal foveolar hyperplasia and brown-fat necrosis.

PMID- 11533850
TI  - [Treatment of schizophrenia: basis and practice. 13th Weissenauer Schizophrenia
      Symposium, Bonn].

PMID- 11533851
TI  - [Glutamatergic neurotransmission in schizophrenics].
AB  - Glutamate is the most abundant amino acid in the brain, where it plays an
      important role as a well-established major excitatory neurotransmitter in the
      central nervous system. It has been suggested that reduced glutamate
      neurotransmission may be involved in the pathophysiology of schizophrenia. The
      glutamate hypothesis of schizophrenia postulates alterations in the glutamatergic
      system as an important neurobiochemical event in the pathophysiology of this
      group of psychotic disorders. An altered glutamate release from synaptosomes
      including a hypofunction of different glutamate receptors (i.e. NMDA receptors)
      from different brain areas have previously been reported. Furthermore, partial
      agonists at the glycine co-agonist site of the NMDA receptor might be a new
      approach in the treatment of schizophrenic symptoms but further studies are
      necessary to clarify the role and efficacy of these substances in schizophrenia.
      Changes in the glutamatergic cortico-striatal connections in schizophrenia could
      precipitate a potential perceptive overstimulation of the neocortex from thalamic
      input and an inhibiting influence of the striatum on the thalamus would modulate
      the information input of the cortex, thereby possibly counteracting the disturbed
      information processing which is relatively characteristic for schizophrenic
      psychoses.

PMID- 11533852
TI  - [Pharmacogenetic strategies].
AB  - Factors influencing treatment outcome to medication include previous history of
      response to medication, duration of illness, ethnicity, and gender; as well as
      genetic factors. These genetic factors influence pharmacokinetic and
      pharmacodynamic effects of specific drugs such as absorption, metabolism,
      elimination, transport across the blood-brain barrier, and drug-target
      interactions. The detection of individual genetic differences in response to
      medication may lead to important new strategies for the treatment of psychiatric
      disorders. With the advent of molecular biology individual differences can be
      determined on the molecular level. The awareness of the importance of
      pharmacogenetic factors has recently led to numerous studies seeking association
      between genetic variants and treatment-outcome. The results however, are
      partially inconsistent. One of the main reasons for this inconsistency may be
      accounted by heterogeneity of study designs. As in genetic studies of complex
      phenotypes, several replications are required before a result can be accepted,
      first 'guidelines' have been proposed to make those studies comparable. These
      'guidelines' and study results will be presented.

PMID- 11533853
TI  - [On the clinical relevance of clozapine-triggered release of cytokines and
      soluble cytokine-receptors].
AB  - Cytokines are pivotal mediators of the interaction between immunocompetent cells.
      Moreover, they mediate the interaction between the immune system and other
      physiological systems, including the CNS. It has been shown recently that the
      antipsychotic drug clozapine stimulates in vivo the release of cytokines and
      soluble cytokine receptors. This holds true for the tumor necrosis factor(TNF)
      system, the interleukin(IL)-2-system, IL-6, and granulocyte colony-stimulating
      factor (G-CSF). The present paper discusses the clinical relevance of these
      findings for the pathophysiology of clozapine-induced side-effects. It is very
      probable that TNF-alpha plays an important role in clozapin-induced fever and in
      the hematopoetic side effects, including agranulocytosis. Moreover, it is likely
      that TNF-alpha and other cytokines are involved in metabolic (weight gain,
      diabetes), cardiac (myocarditis), CNS (sedation) and other rare side effects. The
      mechanisms underlying clozapine-induced immunomodulation are unknown. Hence,
      further studies are very important to enhance our understanding of clozapins's
      side effects and to develop strategies for prevention and treatment.

PMID- 11533854
TI  - [Attempts to overcome the stigma of schizophrenia].
AB  - The results of research into attitudes show clearly that the knowledge, the
      attitudes and views of our society towards psychiatric topics strongly influence
      practical psychiatric services. Those affected report that they are confronted
      with a high degree of prejudice and exclusion which considerably inhibits their
      recovery, their integration and their quality of life even today. Especially
      people with schizophrenic illnesses are affected by stigmatisation and exclusion.
      These are not just caused by a lack of information. Prejudices and misconceptions
      are deeply rooted in our cultural tradition. The negative consequences for the
      treatment and way of life of those affected are such that Asmus Finzen spoke of a
      "second illness" which may be caused by stigmatisation.Set against the background
      of the vulnerability-stress-paradigm, the social consequences can result in
      stressors. Disadvantages in terms of societal participation, negative assessments
      and humiliating discrimination can undermine self-esteem, ability to cope and
      compliance and thereby hinder the recovery process and strengthen remaining marks
      of the illness. Since there is extensive informed understanding about these
      problems, the discussion focuses increasinlgy on questions about what psychiatry
      and those working in psychiatry can contribute to reverse this negative attitude.
      This is the aim, for example, of the World Psychiatric Association's
      international awareness campaign, which uses modern communication techniques to
      try to counter the myths and misunderstandings surrounding the schizophrenic
      illness and its name. The study being introduced here was carried out in
      conjunction with the Society for Mental Health Tyrol. It was attempted to
      discover how information should be conveyed in order to change the attitudes of
      school pupils. On the basis of these results, we have begun to offer information
      sessions in schools throughout the Tyrol.

PMID- 11533855
TI  - [How can we determine the outcome of schizophrenic diseases?].
AB  - With the successful introduction of neuroleptics in the 1950s and improvement of
      medical and psycho-social care a major breakthrough toward a positive development
      of the schizophrenic disease in both the short and especially the long term
      seemed accomplished. By now the initial euphoria has given way to at least
      temporary disillusionment. How serious is the actual scale of the handicap? How
      often do permanent health- and social impairments occur? After naming the
      methodological problems of passed follow-up-studies theoretical requirements of
      future studies of the course of schizophrenic diseases are being described.

PMID- 11533856
TI  - [How far is psychopathology still meaningful for the treatment of
      schizophrenia?].
AB  - The paper gives reasons for the view that psychopathology has to be not only the
      fundamental method for clinical psychiatry, but also an essential prerequisite
      for a rational therapy of schizophrenia and related disorders. Because
      schizophrenic patients present very different types of psychopathological cross
      sectional syndromes, the choice of a distinct neuroleptic or antidepressant
      compound and their dosage has to be guided along the psychopathological target
      syndrome. The clinical-therapeutical effects of neuroleptics and antidepressants
      are above all symptom- (Freyhan) or syndrome-directed. The differentiation of
      positive and negative symptoms, acute and chronic or residual schizophrenia, or
      of the prodromal symptoms according to contemporary approaches seems to be not
      sufficient for the early detection of psychopathological predictors of an
      impending psychosis and the special indication and choice of a distinct drug and
      dosing strategy. This is valid for maintenance treatment of patients in
      remission, for early intervention in the prodromal stages before the first and
      later psychotic episodes and in preventing relapses. Relapse rates can be reduced
      by a low dose maintenance therapy with basic symptom oriented early adaptation of
      the dosage in the prodromes before psychotic remanifestations. Some
      presuppositions of an effective psychopharmacological and psychological therapy
      in view of clinical psychopathology (K. Schneider) and the "phenomenological
      attitude" (K. Jaspers) are outlined. A necessary condition for the secondary as
      well as for the primary prevention of psychotic episodes is the detailed
      knowledge of the interindividual different dynamic and cognitive basic symptoms,
      defined in the Bonn Scale BSABS, that are experiential in kind and not identical
      with the negative and behavioral "Prodromal and Residual Symptoms" of DSM and ICD
      10. The early detection and preventive intervention of schizophrenic psychoses is
      most likely possible by means of a subtle, descriptive-analytical phenomenology
      and psychopathology. Also "chronic" patients beyond acute psychoses, e. g. those
      with persisting pure residues, characterized not by true negative, but by basic
      symptoms, often respond to distinct atypical neuroleptics and/or antidepressants.
      The knowledge of the prodromal symptoms and the coping strategies, frequently
      developed by the patients themselves, is an essential component of a basic
      symptom oriented psychoeducational concept.

PMID- 11533857
TI  - [The schizophrenic spectrum: an epidemiological viewpoint].
AB  - In epidemiological terms there is no clear demarcation between health and
      illness. This is also true for the schizophrenic spectrum, where sub-clinical
      (sub-syndromal, sub-diagnostic) syndromes embrace schizotypical, schizoid and
      paranoid personality disorders and personality features, which in the general
      population are much more prevalent than schizophrenias themselves. Early
      recognition of risk cases and mild cases is decisive for prophylaxis. Several
      diagnostic instruments are available for this purpose, but satisfactory
      confirmation of their predictive power and validity by prospective studies is
      lacking. Alongside traditional, clinical research on schizophrenia, future
      epidemiological research, focusing increasingly on the whole schizophrenic
      spectrum, may be expected to yield important new insights confirming a
      dimensional rather than a categorical distribution of traits and syndromes and
      providing powerful arguments against the discrimination and stigmatisation
      suffered by schizophrenic patients.

PMID- 11533858
TI  - [Therapy of subclinical (subdiagnostic) syndromes of schizophrenia spectrum].
AB  - Since 1911, when E. Bleuler thought of the so-called latent schizophrenia as the
      most frequent type of schizophrenia, but most seldom diagnosed as such, the
      question, whether there exist abortive forms of schizophrenia, was discussed
      again and again; so in 1932 by Mayer-Gross, who devoted to the uncharacteristic
      onset of schizophrenia a special chapter, in 1938 by Stern (so-called borderline
      neuroses) und in 1949 by Hoch and Polatin (pseudoneurotic schizophrenias). Since
      the 50s Huber had described by means of follow-up studies the uncharacteristic
      basic stages occurring long before the onset and after remission of the florid
      symptomatology, in 1957 the cenesthetic schizophrenia and in 1961 and 1966 the
      asthenic or pure defect of schizophrenia, which he also counts to the subclinical
      syndromes or formes frustes of endogenous psychoses just as the endogenous
      juvenile-asthenic failure syndromes, the larvate schizophrenia, the endogenous
      obsessive-compulsive disorder and the circumscribed cenesthopathy. The
      recognition of these subthreshold stages and types of the schizophrenia spectrum,
      which cannot be diagnosed by valid diagnostic criteria for schizophrenia, is the
      presupposition for an adequate therapy. The patients complain about subjectively
      experienced mainly dynamic, affective, cognitive (thought, perception and action
      disturbances), cenesthetic and vegetative basic symptoms, can be registered and
      documented by the Bonn Scale BSABS. We will deal with symptomatology, course and
      therapy of the mentioned sublinical syndromes. The psychopharmacological
      treatment is chosen according to the psychopathological cross-section picture and
      will be continued until improvement or remission of the symptomatology and after
      stepwise reduction stopped. If dynamic and affective basic symptoms predominate,
      we prefer antidepressants (e. g. amitriptyline-type or the newer SSRIs), in case
      of prevailing cognitive and cenethetic basic symptoms neuroleptics, today mainly
      atypical ones. In the past also classical neuroleptics, e. g. haloperidol,
      fluphenazine or pimozide in low dosage of or low potent drugs as thioridazine or
      perazine have proved to be worthwhile.

PMID- 11533859
TI  - [New concepts of schizophrenic sub-syndromes - consequences for treatment].
AB  - Etiopathogenetic research gives rise to the suspicion that the classifications on
      hand pool heterogeneous disturbances under the heading of schizophrenia. This has
      drawn increasing attention to the necessity of identifying schizophrenic
      subsyndromes. Investigations using factor analysis revealed convincingly three
      major groups of schizophrenic symptoms: 1. a "negative factor", 2. a
      "psychoticism factor", comprising delusions and hallucinations and 3. a
      "disorganization syndrome" whose cardinal item is formal thought disorder. These
      studies have not yet furnished final results, but already opened insights
      enabling the conceptualization of syndrom-oriented therapies. The observation
      that the psychoticism symptomatology occurs in the frame of a "dynamic
      instability", based on a thymopsychic hyperreactivity, is in this regard
      especially important. In schizophrenic patients this hyperreactivity may be
      caused by secondary biological compensation mechanisms - such as perhaps an "up
      regulation" of postsynaptic dopamine receptors. "Classic" neuroleptics can only
      correct the dynamic instability and thus eliminate psychoticism symptoms and
      reduce the accentuation of disorganization symptoms. They have, however, no
      influence upon negative symptomatology and can moreover aggravate "secondary"
      negative symptoms and especially impede cognitive functions. New "atypical"
      neuroleptics do not produce these side effects. They seem to have a reducing
      influence on negative symptoms and to improve cognitive functions. In each
      neuroleptic therapy a stepwise drug withdrawal should make clear whether or not a
      continous treatment is necessary. In the first case the needed efficacious dosis
      must be identified. The patients must learn to recognize relapse prodromes and to
      prevent the appearance of acute episodes through appropriate modifications of the
      medication. This strategy requires the combination with adequate
      psychotherapeutic methods enabling the patient to master persistent negative and
      disorganization symptoms in the best possible way.

PMID- 11533860
TI  - [Is there a primary prevention of schizophrenic psychiasis?].
AB  - At first, this article comprises the innovative programme of the international
      "Early Detection and Intervention" research and then shows results of the
      "Cologne/Bonn Early Recognition - CER" project on schizophrenia, the first
      longterm prospective study on patients in potentially initial prodromal stages
      prior to the first psychotic manifestation. At re-examination at an average of
      9.6 years later, 79 of 160 patients had subsequently developed a schizophrenic
      psychosis according to DSM-IV criteria. Prediction values for the complete range
      of prodromal symptoms, for 5 subsyndromes and for individual symptoms were
      assessed. Best prediction values with a high positive predictive power (71 - 91
      %) and a low rate of false-positive predictions (7.5 - 1.9 %) were achieved for
      10 symptoms and symptom complexes mainly out of the group of thought, speech and
      perception disturbances. As only unsatisfactory prediction values for other
      prodromal symptom definitions were reported, e.g. the commonly used DSM-III-R
      definition, empirical evidence for the possibility of diagnosing schizophrenia as
      early as in the initial prodromal stage, has been found for the first time. In
      the following, this article considers essential initiatives for the development,
      performance and evaluation of a promising early intervention programme based on
      the results found. In Germany, within the project unit "Early Recognition and
      Intervention" of the competence network "Schizophrenia", such a programme has
      been initiated. Late prodromal stages are defined by attenuated or transient
      psychotic symptoms and early prodromal stages by the presence of at least one of
      the highly predictive prodromal symptoms from the CER-study or decline in psychic
      functions in combination with other risk factors. Intervention strategies are a
      multimodal psychological programme for the intervention in early prodromal stages
      and a combination of psychotherapy with atypical neuroleptic drugs in the late
      prodromal stages. If such strategies were able to suppress the progress to first
      psychotic episodes, this prevention could be classified as a primary prevention,
      not with regard to the prodromal symptoms but to frank/manifest schizophrenia.

PMID- 11533861
TI  - [Strategies of long-term medication in schizophrenia].
AB  - Schizophrenia is a relapsing disorder. The main goal of neuroleptic long-term
      treatment is relapse prevention, which is empirically well proven. Availability
      of different kinds of treatment strategies including new antipsychotic drugs with
      improved risk/benefit profile allow long-term treatment to be individually
      tailored. Treatment guidelines developed mainly by the scientific medical
      societies can help the practitioner in making the right decisions.

PMID- 11533862
TI  - [Etiological and therapeutic aspects of schizoid and schizotypal personality
      disorder].
AB  - Following the introduction to the history of the concepts of abnormal
      personality, with regard to the schizoid and schizotypal forms, we present their
      systematic assessment in the modern classification systems.Both, the schizoid and
      schizotypal forms, are usually considered as schizophrenia-spectrum disorders.
      Biological and clinical data indicate relations to other axis-I disorders as
      well. However there are few systematic and strictly controlled studies on the
      psychotherapeutic and pharmacological treatment of schizotypal and schizoid
      personality disorders. Basic theoretic assumptions concerning both treatment
      concepts - for personality disorders in general, and especially in schizoid and
      schizotypal personality disorder - are given. Finally the role of neuroleptics
      and antidepressants for schizophrenia-spectrum disorders is discussed. New
      possibilities may emerge from the use of the recently developed atypical drugs,
      but further research in randomised studies is needed. Current prospective studies
      on early detected schizophrenia-spectrum disorders will broaden our knowledge
      about prevention and therapy.

PMID- 11533863
TI  - [Psychological therapy of patients with schizophrenia: Trend of the concept
      development].
AB  - In the first stage of the application of behavioral methods the improvement of
      the level of function in the social environment was in the lime-light. In the
      single case the restoration of a structured daily routine represents the
      presupposition for a cognitive therapy. Its aim is the building up of
      intrapsychic controlling processes that support the structuring of embarrassing
      experiences. E.g., it is possible by controlled introspection to identify
      stressors, perceived by the patients themselves, leading to overstrain-reactions.
      The reduced capacity to be subjected to stress has to be made understandable to
      the patient who is encouraged to intentionally use avoiding reactions. By the
      insight in such connections the problem is comprehended and the anxiety reduced.
      In the psychoeducation the instruction of the family members about basic symptoms
      proved to be useful to put the behavior of the patients in the right place and to
      correct misunderstandings. A skeleton-concept is needed, containing many
      individual components that can be variably used. The completion of these
      components is the aim, because the very heterogeneous features of the residual
      syndromes of schizophrenic disorders require such an "open concept".

PMID- 11533864
TI  - [Cognitive behavioral treatment of schizophrenia - ways towards differential
      indication].
AB  - Cognitive-behavioral treatment of schizophrenia is increasingly manifold and
      sophisticated. The empirical evidence for the efficacy with respect to relapse
      prevention is most convincing for family psychoeducation. Furthermore, treatment
      programs for patients and relatives could show efficacy in randomized controlled
      intervention studies. These programs are designed to improve the patients
      cooperation and medication compliance, to enhance skills to manage early signs of
      relapse and to give support in stress management. Work with relatives aims at
      easing the burden of care, improving the knowledge concerning the illness and
      enhancing the coping skills of the relatives. A randomized clinical trial of our
      group could show a significant reduction of the readmission rate by a combined
      patient and relative-focused intervention. Even five years after completion of
      therapy we observed a clinical meaningful effect. We found that a favorable
      prognosis and good social adaptation was a positive predictor of treatment
      success. However, further research should investigate differential effects in
      more detail. Symptom reduction is another important issue of cognitive-behavioral
      treatments. The cognitive therapy of persistent positive symptoms resistant to
      neuroleptic treatment has recently attracted attention. Three work groups in
      Great Britain could show independently that positive symptoms could be reduced
      significantly by strategies of cognitive-behavioral treatment. However, treatment
      strategies for the reduction of negative symptoms remain to be developed and
      evaluated. With respect to the implementation of the mentioned treatment
      strategies in the routine care there are several problems that will be outlined
      finally.

PMID- 11533865
TI  - [Psychotherapy for schizophrenia].
AB  - Based on different theoretical concepts, psychotherapeutic methods in the
      treatment of schizophrenia reach from clinical pragmatism, psychoanalysis,
      learning theory, cognition and communication psychology to concepts of systems
      theory. Both the German (DGPPN) and the American (APA) practice guidelines for
      the treatment of schizophrenic patients don't separate psychotherapy, social and
      rehabilitation measures strictly. So a specific psychotherapy for psychotic
      patients seems to be missing. A better relationship between patient and expert is
      fundamental for building up a ??? therapeutic liaison. For that purpose, the
      disease concepts of both sides must be carefully explained and integrated ("Basic
      psychotherapy").

PMID- 11533866
TI  - [8. Awarding of the Kurt-Schneider scientific prizes].

PMID- 11533867
TI  - [Public Health 2000. Proceedings of the continuing education congresses for
      physicians and social workers in public health service, Erlangen 1999, Ingolstadt
      2000].

PMID- 11533868
TI  - [Methods and consequences of pre-natal diagnostics].
AB  - Prenatal medicine is a young subdiscipline of modern obstetrics. It applies
      diagnostic methods like amniocentesis, chorionic villus sampling and foetal blood
      sampling. The latter is not only a diagnostic procedure but opens access to the
      foetal circulation and therefore to foetal therapy. Aim of prenatal diagnostic
      procedures is the most exact diagnosis of the foetal condition as basis for
      rational obstetrical decisions. If a foetal disease is diagnosed, decisions are
      in principal similar to the postnatal situation, but therapeutic options are
      reduced. Decision making in prenatal medicine always has to take maternal and
      foetal interests into account. We have to consider that not the methods but the
      intention and actions of the persons involved may cause an ethical dilemma. It
      must be our aim to use the methods of prenatal medicine with the utmost
      responsibility.

PMID- 11533869
TI  - [Pregnancy and substance dependency].
AB  - Substance dependency in pregnancy leads to severe health risks for the expecting
      mother and for the foetus and the new-born. The problem of substance dependent
      pregnant women lies not only in the use of illegal substances but also to a high
      degree in the use of legal substances such as alcohol and nicotine. In contrast
      to most other substances of abuse, opioids do not show cytotoxic or teratogenic
      characteristics. The primary goal should be the stabilisation of the patient and
      a reduction of additional illicit consumption. The ideal goal of abstinence is
      difficult to reach and often puts the women under enhanced risks. Detoxification
      after week 32 should not be undertaken in order to avoid preterm delivery. It
      should be standardised that a multiprofessional and interdisciplinary
      therapeutical care leads to a stabilisation in opioid dependent pregnant addicts
      and therefore improves the outcome for neonates. Special awareness needs to be
      addressed towards the diversification of opioid maintenance therapy. Based on the
      positive results in opioid maintenance therapy in pregnant opioid dependent
      women, it will be required to establish standards. Furthermore there is a need to
      establish consistent guidelines for the treatment of the neonatal abstinence
      syndrome.

PMID- 11533870
TI  - [Children's well-being under adversive situations in life: new results of studies
      on resiliency].
AB  - The risks of modern life increasingly endanger the well-being of children. There
      is a rising number of scientific investigations demonstrating that a significant
      number of children growing up under highly adversive conditions of life resist
      developmental risks they are exposed to. What are the specific characteristics
      and competencies of these children supporting resiliency? What qualities of
      developmental environments strengthen children and their well-being? The
      challenges for modern education resulting from the findings of resilience
      research are discussed.

PMID- 11533871
TI  - [Migration and health: public health services coordinating health related
      variety].
AB  - About 9 % of the German population is of immigrant descent. Correlations between
      migration and health have recently been focused on by health and social sciences
      in Germany. Migration due to different motivations itself strongly affects the
      health status of individuals and subpopulations. Therapeutic institutions on an
      individual level and public health services in Germany will need further
      development towards professional intercultural health care. An international
      workshop on the topic of migration and health in March 2000 illustrated the
      importance of the public health services and their opportunities in co-ordination
      of the health related multicultural variety. Migration generally was regarded
      being an asset to health in the community. Improvement of verbal communication
      skills and of the medical expert opinion practice towards culturally sensitive
      health care were pointed out being major objectives for the public health
      services as were prevention and health care programs for children and for
      psychosocially endangered persons within the immigrant population.

PMID- 11533872
TI  - [The Bavarian Health Survey--goals and selected results].
AB  - The Bavarian Health Survey (1998/99) is a new element in the Bavarian health
      reporting system. It was conducted in close connection with the German Health
      Survey as a combination of a questionnaire and health examination survey with
      participation of the Bavarian local health offices. Based on a random sample of
      more than 1,800 persons aged 18 to 79 years, life-prevalence data on diseases of
      the metabolic system, selected laboratory results and obesity are reported.

PMID- 11533873
TI  - [Population-based health monitoring via computer-assisted telephone interviews in
      Bavaria].
AB  - From June 1999 until May 2000, 2051 computer-assisted telephone interviews
      concerning health and health related behaviours were assessed in Bavarian
      households. The aim of the study was the evaluation of the validity and
      representativity of this data by a comparison of selected variables from the
      Bavarian Mikrozensus-survey 1999. The distribution patterns of the marital
      status, the size of the households, the gainful employment, the household-netto
      income, the school qualification and of the smoking status correspond well with
      those of the Mikrozensus 1999. As often found in questionnaire based surveys, a
      disproportionately high rate of participation of highly educated persons was
      observed. This led to an effect only in terms of a too small rate of persons with
      a low household-netto-income. Within the study, two different designs were
      compared. The commitment of the telephone numbers to a gender for an equal
      quotation of men and women led to an under-representation of single-households
      and therefore also of unmarried persons, but it had no effect on the other
      characteristics. The results of this study show, that the method of computer
      assisted-telephone interviews is a valid and cheap basis for the establishment of
      an exhaustive health surveillance system in Germany.

PMID- 11533874
TI  - [Social work and health care = clinical social work competence and profile in an
      area that is hard to survey].
AB  - From the very beginning professional social work has been involved in health
      care. However, in our post modern society this area of competence has to be
      improved, and in order to compete with new health professions, a clear
      distinction has to be made. This is shown in important points of modern social
      work: Society perspective (health behaviour and public health circumstances), WHO
      perspective (health promotion) and psycho-social perspective (health care in
      social services). Health care under most difficult conditions asks for
      specialised competence that is to be developed in Germany as "Klinische
      Sozialarbeit" referring to international clinical social work standards.

PMID- 11533875
TI  - [Assessment of additional health care needs of persons with restricted competence
      in daily life: problems and possible solutions].
AB  - A brief general view was given on the public German care insurance. Stressing
      somatic care, persons with restricted competence for daily life activities are
      recorded insufficiently. An instrument for documentation of those restrictions
      was presented.

PMID- 11533876
TI  - [The new Protection against Infection Act].
AB  - The emergence of new infectious diseases and, as a result of globalisation,
      exposure to diseases that had already been largely eradicated in the Federal
      Republic of Germany show how important it is to put a Protection against
      Infection Act into place that matches a current requirement profile. A sine qua
      non for targeted action is a valid data pool on infection epidemiology and its
      evaluation on the regional, Laender and federal levels. Under the recent Act,
      more effective use is to be made of laboratory diagnosis technologies, and the co
      operation between the medical profession, public health services and scientists
      intensified to enhance the protection of the general public against infections.
      Of special importance here are the tasks that fall to the health office as lower
      health authority with its subsidiary services and in its function as the partner
      and advisor of the citizens and the inpatient and outpatient health care
      services. Regulations covering the reporting system, vaccinations and
      immunizations, hospital hygiene, schools and community facilities, food trade,
      water for human use, work with pathogens have been rendered more precise and/or
      updated.

PMID- 11533877
TI  - [Current challenges on hospital hygiene].
AB  - Although microorganisms are the main cause of nosocomial infections, they are by
      no means their only determinants. Patient-associated factors play a major role
      (especially immune status), the therapeutic conditions (personnel behaviour,
      'devices') and the patient's environment. The hospital infection control team is
      responsible for implementing and operating an efficient and cost-effective
      infection control and prevention system. Scientific data must be evaluated and
      every effort made to continuously improve recommendations. In order to implement
      an efficient and cost-effective infection control and prevention system, the
      infection control team must formulate sound, evidence-based recommendations and
      question established 'rituals'. Inappropriate measures, e. g. the routine
      disinfection of floors in wards and hallways place a burden on staff, patients
      and the environment, and distract staff from other critical measures such as
      proper hand hygiene. Nosocomial pneumonia, urinary tract infections, surgical
      wound infections and catheter-associated sepsis are the commonest hospital
      acquired infections, and Intensive Care Units have become the foci of antibiotic
      resistance. Although the antimicrobial resistance situation is better in Germany
      than in other countries, e. g. Eastern and Southern European countries and the
      USA, substantial regional differences exist. The increase in methicillin
      (oxacillin) resistant S. aureus (MRSA) is particularly worrying. Building up an
      effective surveillance system for nosocomial infections, as demanded by the new
      German infection control act has far-reaching implications and entails recording
      risk-adjusted infection rates (KISS project = Hospital Infection Surveillance
      System of the National Reference Center for Hospital Hygiene in cooperation with
      the Robert Koch-institute). Proper collaboration between hospital staff in
      implementing infection control measures, and especially hand hygiene is of
      paramount importance.

PMID- 11533878
TI  - [Hygiene of bathing waters].
AB  - Bathing is possible without any epidemic risk in Southbavarian lakes. Limit
      values according to the water monitoring by the EC-Directive 76/160/EC were
      rarely exceeded and occurred only in 0.3 to 2.1 % of the samples from 1990 to
      1998. In river waters, however, limit values occurred in 17 to 35.3 % of the
      samples and one should beware of bathing there. In 1999 some lakes became fecally
      polluted by overflows which could be documented by high numbers of total
      coliforms but not by Escherichia coli. Subsequently total coliforms functioned as
      an important hygienic parameter. Therefore, total coliforms should not be
      abolished in the revision of the EC-Directive. Water monitoring of little lakes
      further revealed that the future limit value of 100 fecal streptococci in 100 ml
      was exceeded in more than 50 % of the samples. Enterohaemorrhagic E. coli were
      demonstrated in 2 % of the surface water samples. Thermophilic campylobacters
      could be isolated from 17.4 % of bathing water samples which were faultless
      according to the hygienic parameters of the EC-Directive. In this respect all
      possibilities should be utilized to minimize fecal pollutions at bathing places.

PMID- 11533879
TI  - [Knowledge and clinical action].

PMID- 11533880
TI  - [Psychosomatic aspects of obesity].
AB  - Overweight and obesity are widespread in industrial countries and are considered
      to be serious health problems in these countries. Population-based studies in
      Germany have shown that between 12 and 18 % of the adult population is obese.
      Overweight and obesity are accompanied by a large spectrum of health disorders
      and extreme psychosocial burdens. Besides the hereditary disposition, the life
      style including both intra- and inter-individual aspects determines the complex
      etiology of obesity. Within the collective sample of the obese, one sub-sample is
      the "psychogenic obese" i. e. in which psychiatric disorders lead to a change in
      both eating and exercise behavior, the result then being a continuous positive
      energy reserve in the form of overweight and obesity. The paper describes the
      psychosocial problems of obese persons; especially the controverse question with
      regard to psychiatric morbidity in general and eating disorders in particular are
      emphasized. The results of past, mainly behavioral oriented treatment concepts
      are presented and various concepts beyond single school orientation are
      discussed. Finally, the problems with psychiatric psychological diagnostics in
      those obese patients with the request for surgical weight reduction within the
      context of insurance coverage and the surgeons are presented.

PMID- 11533881
TI  - [Study quality and effect-sizes - a metaanalysis of EMDR-treatment for
      posttraumatic stress disorder].
AB  - Although the good efficacy of eye movement desensitization and reprocessing
      (EMDR) in the treatment of patients with PTSD is up to now documented by a number
      of studies, this new treatment technique is still the target of highly
      controversial critique. Our meta-analysis tries to answer the question of whether
      EMDR-therapy studies with higher quality standards achieve better results than
      others. Therefore, all published studies underwent a scoring procedure of study
      quality and effect sizes were computed. It can be shown that carefully planned
      studies, including treatment by well-trained therapists and with a sufficiently
      high number of treatment session achieve better results compared to studies with
      low methodological standards.

PMID- 11533882
TI  - [The influence of psychosocial factors on mental well-being and physical
      complaints before and after undergoing an in-patient abortion].
AB  - In this study, 57 women were examined in terms of the influence of different
      psychosocial factors on their subsequent mental well-being and physical
      complaints one day before, one day after, and 3 months after undergoing an in
      patient abortion. Furthermore a control group of 40 in-patients (women with
      pregnancy related problems) were included in the study. The results show that
      prior to the abortion, most women reported a multitude of psychological and
      physical problems. However, it was also shown that for the majority of the women
      interviewed, mental well-being and physical complaints improved significantly one
      day and 3 months after the abortion. While feelings such as relief predominated
      immediately postoperatively, after 3 months, participants reported feeling
      cheerful and interested in activities. Further, it was demonstrated that women
      whose general mood was more pronouncedly anxious-depressive one day prior to
      operation later (after 3 months) reported many complaints and worse well-being.
      It appears that these women were not able to experience the abortion as a problem
      solutions. Finally, the great importance of the quality of their relationship and
      cohesion was demonstrated in the decision to abort, while pregnancy counselling
      was found to have no effect.

PMID- 11533883
TI  - [Validity of operationalized psychodynamic diagnostics].
AB  - The paper describes results of "operationalized psychodynamic diagnostics" (OPD)
      with 54 adolescent and young adult drug addicts prior to outpatient family
      therapy. Focus of investigation is the prognostic and factorial validity of the
      OPD-system. Furthermore, relationships between conflicts and psychic structure
      are investigated. The use of the OPD-system allows a clinical description of the
      patient sample. Thus, adolescent drug addicts are characterized by autonomy
      versus dependence and self-esteem conflicts. A neurotic or sometimes borderline
      level is found on the structure axis. Low scores on the structure axis are
      significantly correlated with self-esteem conflicts. There is some evidence for
      the prognostic validity of the OPD I axis. However, prognostic validity of the
      structure and conflict axes require further research.

PMID- 11533884
TI  - [The family emotional involvement and criticism scale].
AB  - The construct of expressed emotion is regarded as one of the most important
      predictors of the course of schizophrenia and has also proven to be a predictor
      of the course of depressive disorders, psychosomatic disorders and physical
      illness. Despite its clinical significance, the utility of the EE-construct has
      been limited since measurement by interview is time-consuming, and to date only
      applicable to psychotic illness. Questionnaires as a practicable alternative to
      the structured interview are also mostly applicable solely to psychotic
      disorders. One exception is the Family Emotional Involvement and Criticism Scale
      (FEICS, Shields et al.). This questionnaire allows a general assessment of EE and
      thus a practical application of EE to the general area of family research. In a
      sample of n = 202 patients, the German version of this instrument proved to be
      reliable in our research. The two-factor structure of the original American
      version was replicated. We found good correlation between the measured factors,
      and clinical and other diagnostic markers particular to family pathology. This
      questionnaire is therefore a brief, reliable and valid instrument for measuring
      EE in many disorders.

PMID- 11533885
TI  - [The testing and validation of the German version of the impact on family scale
      in families with children with disabilities].
AB  - Despite increased interest in the wellbeing of families with children with
      chronic conditions and disabilities, instruments to assess family impact of
      health conditions are still lacking in German speaking countries. The Impact on
      Family Scale has been developed in the Anglo-american literature as a self report
      instrument to assess the consequences of chronic conditions and disability in
      childhood and adolescence for the family. The present paper describes the
      translation and psychometric testing of a German version of the Impact on Family
      scale (Familien-Belastungs[FaBel]-Questionnaire). The questionnaire contains 33
      Likert-scaled items to assess the general negative impact of parents, the
      description of social relationships, the concern for siblings, the financial
      impact and problems in coping as well as a total score. The FaBel questionnaire
      was used and tested for psychometric criteria of reliability and validity in a
      cross-sectional study of 273 families with children with chronic conditions and
      disabilities. The results of this psychometric testing of the FaBel-Questionnaire
      show acceptance by responders, acceptable construct validity, good internal
      consistency and discriminant validity. The psychometric structure of the
      questionnaire corresponds with psychometric results with another German
      population of children with chronic conditions. The results suggest the
      applicability of the instrument to assess family impact of chronic disease and
      disability in children and adolescents.

PMID- 11533886
TI  - [Predictors of therapeutic success in inpatient psychosomatic rehabilitation of
      musculo-skeletal diseases].
AB  - The aim of the present study was to identify pre-program factors and treatment
      related changes predicting short-term (end of treatment) and long-term (three
      years after therapy) treatment success in inpatient psychosomatic rehabilitation
      of musculo-skeletal diseases. Discriminant function analysis of pre-program
      factors above all revealed a positive influence of a non-existing wish for social
      compensation, a smaller amount of medical treatment and lower sick leave for
      short- and long-term therapeutic outcome. Analysis of treatment related changes
      showed, that an improved mobility, well-being and an ameliovated self-esteem had
      prognostic value for short-term success. Long-term success was predicted by
      improved well-being, an improvement of understanding between physician and
      patient and by decreased depressive symptoms in the course of treatment.

PMID- 11533888
TI  - [Institutional outpatient wards - It was a long way to Tipperary].

PMID- 11533889
TI  - [Medical treatment of psychiatric disorders in alcoholics].
AB  - PURPOSE: Epidemiological studies show that alcoholics have a high life-time
      prevalence of psychiatric illnesses, particularly of anxiety, depressive and
      schizophrenic disorders. But the complex relationships between elevated alcohol
      consumption and psychiatric symptomatology frequently Iead to problems in finding
      diagnosis and thereafter in planning therapeutic strategies. METHODS: In this
      article the results of the studies concerning the medical treatment of
      psychiatric comorbidity of alcoholics are critically reviewed. RESULTS: According
      to the available results a therapy with antidepressive drugs indicated in
      alcoholics with depression lasting over 14 days. Anxiety disorders seem to have
      little influence on the course of alcoholism. Thus, an anxiolytic medication has
      to be considered carefully in view of the addiction potency of tranquilizers.
      There is a paucity of data concerning drug treatment of schizophrenics with
      alcohol abuse. Thus far only a few studies have shown an effect of a drug
      treatment of the psychiatric comorbidity on the drinking behavior. CONCLUSION:
      There is a lack of studies on specific treatment strategies of psychiatric
      comorbid alcoholics, particularly of schizophrenics with alcohol abuse.

PMID- 11533890
TI  - [Unplanned discharge in a psychiatric day clinic - argument for an individualized
      approach].
AB  - OBJECTIVE: Drop-outs, respectively unplanned discharges in psychiatric therapy
      are often explained by so-called lack of insight into the disease or difficult
      circumstances of admission. We were interested in the question how often drop
      outs are noticed in a voluntarily day clinic setting where nearly all psychiatric
      diseases are treated. METHOD: The charts of all patients discharged in 1998 (n =
      65) were screened referring to their mode of discharge. RESULTS: 31 patients
      (47.7 %) regularly ended their treatment. An unplanned discharge was registered
      with 34 patients (52.3 %). CONCLUSIONS: The statistically relevant term of drop
      out does not appear to be the right one to deal with the individual treatment
      situation and the motivation for the limitation of treatment. A typology of
      prematurely ended therapies is developed.

PMID- 11533891
TI  - [Buprenorphine in pregnancy].
AB  - The treatment of opioid dependence during pregnancy is a major challenge for
      doctors, social workers and gynaecologists. Continuous drug abuse during
      pregnancy can lead to a variety of complications in the mother, fetus and
      neonate. lt is recommended practice to maintain pregnant opioid-dependent women
      with synthetic opioids and according to international guidelines, methadone is
      the recommended substance so far. However, a neonatal abstinence syndrome (NAS)
      of varying severity is observed in 60 - 80 % of the neonates with even a longer
      course of duration in comparison to the NAS after heroin consumption during
      pregnancy. NAS is characterised by tremor, irritability, hypertonicity, vomiting,
      sneezing, fever, poor suckling, and sometimes convulsions. Recent studies have
      investigated the safety and efficacy of other synthetic opioids like sublingual
      buprenorphine for the treatment of pregnant patients. We present a 22 year old
      opioid-dependent woman, who has been maintained continuously on buprenorphine for
      3 years. During the treatment episode she delivered two healthy newborns and both
      did not show any symptoms of NAS. The maintenance therapy with buprenorphine
      proved safety and efficacy during pregnancy, the mother was free of continuous
      heroin abuse, verified through supervised urine-toxicology. The quantitative and
      qualitative difference in NAS may be explained by the partial mu-receptor agonist
      and kappa-antagonist receptor profile of buprenorphine compared to pure mu
      agonist action of methadone or heroin.

PMID- 11533892
TI  - [Vocational rehabilitation of the mentally ill - an evaluation of the Vocational
      Rehabilitation Center in Zurich, Switzerland].
AB  - OBJECTIVE: The aim of the Vocational Rehabilitation Center in Zurich (VRC) is to
      reintegrate mentally ill persons into the primary labour market, mainly by
      prevocational training followed by continuous professional support for employed
      individuals. The present study evaluated the impact of the VRC. METHODS: The job
      and financial situation of 68 trained persons was assessed up to two years after
      the training. Additionally, their vocational history and sociodemographic data
      were analysed. RESULTS: Before the training, only 9 % had a job, while two years
      after the course 42 % were employed in competitive jobs. On the other hand, using
      an ordinal scale, two years after the training, 78 % of the patients were found
      in a better job situation than before the course. Likewise, the financial
      situation of 52 % of the clients has improved within those two years. The
      strongest correlation with success was the intensity of support after the
      training. CONCLUSIONS: The VCR is effective in training mentally ill patients for
      the primary job market. Continuous professional support is vital for ongoing
      success.

PMID- 11533893
TI  - [The importance of proficiency in the German language in development and
      treatment of psychiatric diseases].
AB  - The study investigates the relations between proficiency in German language and
      manifestation and course of psychiatric diseases in migrants from Eastern Europe.
      Analyses were conducted for all migrants, who were treated in the local
      psychiatric state hospital between 1990 and 1996. Results showed that migrants
      with low language proficiency fall sick earlier, are admitted to the hospital
      faster and are kept in hospital treatment longer than those with good German
      language proficiency.

PMID- 11533894
TI  - [The efficacy of an individualized treatment schedule to maintain treatment
      adherence in an urban community mental health center].
AB  - OBJECTIVE: We present an observational study on the efficacy of an individualized
      treatment schedule, which is meant to support treatment adherence in an urban
      community mental health center (CMHC). METHODS: The present investigation was
      carried out in the natural setting of a CMHC in Vienna. During a 3-month period
      we observed the compliance with the appointments and the actions taken by the
      team in response to missed appointments as well as the utilization of the CMHC
      during a follow-up period of 6 months. RESULTS: During the observation period 393
      (19,2 %) of 2049 scheduled visits were missed affecting more than half of the
      patients. Only a minority of patients with low-intensity treatment and a high
      rate of missed appointments had a high risk for discontinuing treatment.
      CONCLUSIONS: Missed appointments in outpatient psychiatric care are a common
      phenomenon but they constitute no major threat to the continuity of care for the
      majority of the patients due to the graduated efforts of the team. The time
      required to make up for missed appointments is considerable but the results of
      the follow-up confirmed the beneficial effects on utilization of psychiatric
      care.

PMID- 11533895
TI  - [Disturbed color vision in endogenous psychoses].
AB  - We examined 50 patients with endogenous depressions and 50 patients with
      schizophrenic psychosis. We found disturbed colour vision in 54 % of the
      endogenous depressions and in 72 % of the schizophrenic psychosis. We discuss the
      aetiopathogenic from disturbed colour vision in the endogenous psychosis.

PMID- 11533896
TI  - ["I am a Misunderstood Being on Earth" - Concept of illness of patients suffering
      from schizophrenic psychosis before and after psychoeducational treatment].
AB  - OBJECTIVE: To determine the effects of a psychoeducational intervention on the
      individual concepts of illness of patients suffering from schizophrenia. METHOD:
      27 patients with a diagnosis of schizophrenia according to ICD-10 were
      interviewed with open ended questions about their concept of illness at admission
      to a day hospital and after 10 weeks of attending a psychoeducational program.
      Questions concerned terminology, diagnosis, prognosis, interventions and
      aetiology. A qualitative analysis of these data is presented. RESULTS: The terms
      used to describe the illness were mostly colloquial. Highly individualized and
      heterogeneous concepts of illness, aetiology and helpful interventions and a
      positive view regarding prognosis prevailed. Changes over time were limited and
      arbitrary. CONCLUSIONS: The concepts offered by professionals were adopted in a
      very limited way, which can be understood in the context of highly individualized
      ways of coping with diagnosis and illness.

PMID- 11533897
TI  - [Unruly passengers - resistance to requests by flight attendants].
AB  - Travelling by airplane is of increasing importance in modern society. Psychiatric
      disorders seldom cause incidents in aircrafts. Scandal sheets and serious
      newspapers as well report on disturbances of a flight by psychiatric patients. Up
      until now psychiatric research is not engaging in unruly flight passengers
      suffering from psychotic symptoms. We describe a passenger who became psychotic
      during an international flight. In addition, we provide an overview over
      publications dealing with unruly passengers due to psychosis and describe similar
      cases.

PMID- 11533898
TI  - ["I stand always in the center" - Individual treatment of a schizophrenic patient
      with concentrative physicotherapy in a psychiatric hospital].

PMID- 11533899
TI  - [Psychiatric classification of ICD].

PMID- 11533900
TI  - [Do we really need health economics in psychiatry? Why do we need health
      economics in psychiatry?].

PMID- 11533901
TI  - Global "burden of disease"-study for psychiatric disorders.
AB  - The Global Burden of Disease (GBD) study was conducted to provide a set of
      summary health measures that would be comprehensive and make available
      information on disease and injury, including non-fatal health outcomes. The main
      objective of the GBD approach was to inform global priority setting for health
      research and to influence international health policy and planning. One of the
      summary measures used was the Disability Adjusted Life Year (DALY). DALYs are a
      common metric for fatal and non-fatal health outcomes and are based on years of
      life lost because of premature death (YLL) and years of life lived with
      disability (YLD). Thus DALYs = YLL + YLD or Burden = Mortality + Disability.
      Therefore, a DALY is one lost year of healthy life. The DALY methodology provides
      a way to link information on disease burden to cost-effectiveness analysis. This
      feature would assist comparative assessments. The WHO plans to refine this
      framework for assessing the outcomes of interventions and their related costs.

PMID- 11533902
TI  - [Methods of comparative economic evaluations of therapies and for rational
      allocation of resources across sectors of health care systems - introduction,
      advantages, risks].
AB  - Because of scarcity of resources, diagnostic and therapeutic procedures in
      medicine increasingly have to be examined not only with regard to effectiveness
      but also with regard to cost-effectiveness, which means with regard to the
      relation between resources used and resulting outcome (however this outcome is
      measured). Primarily, this is true for treatment methods for one and the same
      medical condition. However, economists also consider to evaluate medical
      interventions across heterogeneous medical conditions, in order to rank them with
      regard to their cost-effectiveness. Using quality-adjusted life-years (QALYs) as
      outcome variable, all medical interventions examined can be ranked in QALY-League
      Tables, which could serve as a basis for resource allocation decisions by health
      policy makers or other payers. However, there are methodological as well as
      ethical objections with such an approach.

PMID- 11533903
TI  - [Costs of schizophrenia - what we know (not)?].
AB  - Schizophrenia is regarded as one of the most expensive mental illnesses because
      of its specific symptoms and characteristics. The care of schizophrenic patients
      consumed approx. 2 % of the total German health care expenditures in 1994,
      according to the scarce data provided by routine German health reporting. Despite
      this enormous impact, health-economical research in schizophrenia in Germany is
      widely neglected. While few empirical studies on direct cost of care for
      schizophrenic patients suggest that adequate comprehensive community care in
      Germany during the mid-nineties was about DM 27 000 to DM 28 000 per patient and
      year, there is a serious lackage of cost-effectiveness-studies, relating cost of
      care to outcome. Thus, the most basic data for any health care planning in
      schizophrenia is missing. This paper reviews the studies on cost of schizophrenia
      in Germany. It identifies the most serious knowledge gaps and describes the
      obstacles for an adequate research in this field.

PMID- 11533904
TI  - [Cui Bono or who needs health economics?].

PMID- 11533905
TI  - [Prophylactic long-term therapy of affective disorders with lithium, valproic
      acid and carbamazepine--effectiveness and cost-effectiveness].
AB  - Affective disorders have a substantial public health impact due to morbidity,
      mortality, quality of life impairment and economic implications. There has been
      renewed debate of the efficacy and effectiveness of Lithium in long-term
      treatment of affective disorders. In the present paper current literature is
      discussed with a focus on the routine use of Lithium (effectiveness) and on cost
      aspects. Recent reviews have confirmed the prophylactic efficacy of Lithium in
      bipolar affective disorders. However, there is some evidence that effectiveness
      studies do not hold what efficacy research would promise. Non-compliance is
      likely to be a major reason for this. Lithium response rates have declined in
      recent studies. This may be related to diagnostic change (broader concept of
      affective disorders) and more widespread Lithium use. Non-compliance in patients
      taking Lithium is a primary factor in relapse with substantial cost effects (due
      to inpatient care). Current studies compare Lithium with Valproic
      acid/divalproex, and find cost advantages for the latter possibly due to better
      compliance. A special suicide-preventive effect has only been proven for Lithium.
      To ensure the full prophylactic potential of Lithium compliance needs to be
      improved. Future studies will compare Lithium with Valproic acid/divalproex,
      Carbamazepine and new treatment strategies more detailed.

PMID- 11533906
TI  - [Economic evaluation of the Swiss project on medically prescribed heroin
      substitution treatment].

PMID- 11533907
TI  - [Method determines results: indirect economic costs of alcohol abuse and
      alcoholism in Switzerland].
AB  - OBJECTIVE: The present contribution aims at illustrating the methodological
      problems that may arise from investigating the indirect social costs of alcohol
      consumption. METHODS: In order to estimate the alcohol-related productivity
      losses through excessive morbidity, regression analysis was performed, using data
      from the 2(nd) Swiss Health Survey (1997). For the purpose of sensitivity
      analysis two approaches were used (a) Rice and b) Harwood), and all models were
      calculated with and without smearing-adjustment as well as with and without
      adjustment for confounding variables. RESULTS: The present study shows that small
      changes in method may result in major variations in the estimated total costs. In
      monetary terms, the indirect costs for alcohol consumption in Switzerland through
      excess-morbidity were estimated at between 0.119 billion Francs (model Harwood,
      smearing-adjusted) and 2.175 billions Francs (model Rice, adjusted for
      confounding variables). CONCLUSION: Since many methodological problems in
      estimating the indirect costs of alcohol consumption have not been adequately
      resolved yet, results of those studies have to be interpreted with caution.

PMID- 11533908
TI  - [Hospital financing in in-patient psychiatry via DRG-based prospective payment-
      The Salzburg experience].
AB  - Hospital financing via case-related prospective payment sometimes is suspected to
      be responsible for accelerating the "revolving-door"-phenomenon in psychiatry.
      According to this reasoning, establishing diagnoses-related groups (DRGs) ruling
      a prospective payment system could not only reduce lengths of stay but could also
      simultaneously raise hospitalization and readmission rates. This study analyses
      the Austrian experience after the implementation of such a payment system, the
      "performance-oriented financing of hospitals" (leistungsorientierte
      Krankenanstalten-Finanzierung, LKF) in 1997. Time series analyses based on the
      complete hospital discharge statistics of the Salzburg province were used as
      methods. Results showed that neither length of stay, nor hospitalization or
      readmission rates in psychiatry have substansially changed or deviated from their
      long-term trends after implementation of the LKF system. Other medical
      disciplines have experienced statistically significant changes. The possibility
      to transfer these results to the German psychiatric health care system is
      discussed.

PMID- 11533909
TI  - [Discussion on the contribution by Ulrich Frick].

PMID- 11533910
TI  - [Reply to the discussion by Heinrich Kunze].

PMID- 11533911
TI  - [From "Burden of disease" research to the conception of an integrated care system
      for substance abuse in Ontario].
AB  - The paradigm of evidence-based medicine has become one of the building blocks of
      modern health policy in established market economies. Based on this paradigm, a
      monitoring system for treatment of substance abuse has been developed in the
      Canadian province of Ontario. This monitoring system comprises four main
      elements: availability of treatment places, utilization of specialized health
      services, costs of treatment and outcome indicators. The paper discusses
      difficulties in implementing the system and gives some indications on future
      developments.

PMID- 11533912
TI  - Dominant intermediate Charcot-Marie-Tooth neuropathy maps to chromosome 19p12
      p13.2.
AB  - The hereditary disorders of peripheral nerve form one of the most common groups
      of human genetic diseases, collectively called Charcot-Marie-Tooth (CMT)
      neuropathy. Using linkage analysis we have identified a new locus for a form of
      CMT that we have called "dominant intermediate CMT" (DI-CMT). A genomewide screen
      using 383 microsatellite markers showed strong linkage to the short arm of
      chromosome 19 (maximum LOD score 4.3, with a recombination fraction (straight
      theta) of 0, at D19S221 and maximum LOD score 5.28, straight theta=0, at
      D19S226). Haplotype analysis performed with 14 additional markers placed the DI
      CMT locus within a 16.8-cM region flanked by the markers D19S586 and D19S546.
      Multipoint linkage analysis suggested the most likely location at D19S226
      (maximum multipoint LOD score 6.77), within a 10-cM confidence interval. This
      study establishes the presence of a locus for DI-CMT on chromosome 19p12-p13.2.

PMID- 11533913
TI  - Birt-Hogg-Dube syndrome, a genodermatosis associated with spontaneous
      pneumothorax and kidney neoplasia, maps to chromosome 17p11.2.
AB  - Birt-Hogg-Dube syndrome (BHD), an inherited autosomal genodermatosis
      characterized by benign tumors of the hair follicle, has been associated with
      renal neoplasia, lung cysts, and spontaneous pneumothorax. To identify the BHD
      locus, we recruited families with cutaneous lesions and associated phenotypic
      features of the BHD syndrome. We performed a genomewide scan in one large kindred
      with BHD and, by linkage analysis, localized the gene locus to the
      pericentromeric region of chromosome 17p, with a LOD score of 4.98 at D17S740
      (recombination fraction 0). Two-point linkage analysis of eight additional
      families with BHD produced a maximum LOD score of 16.06 at D17S2196. Haplotype
      analysis identified critical recombinants and defined the minimal region of
      nonrecombination as being within a <4-cM distance between D17S1857 and D17S805.
      One additional family, which had histologically proved fibrofolliculomas, did not
      show evidence of linkage to chromosome 17p, suggesting genetic heterogeneity for
      BHD. The BHD locus lies within chromosomal band 17p11.2, a genomic region that,
      because of the presence of low-copy-number repeat elements, is unstable and that
      is associated with a number of diseases. Identification of the gene for BHD may
      reveal a new genetic locus responsible for renal neoplasia and for lung and hair
      follicle developmental defects.

PMID- 11533914
TI  - Localization of the gene for the intermediate form of Charcot-Marie-Tooth to
      chromosome 10q24.1-q25.1.
AB  - Intermediate Charcot-Marie-Tooth neuropathy (CMT) is an inherited sensory motor
      neuropathy characterized by motor median nerve conduction velocities of 25-45
      m/s. We performed a genomewide search in an Italian family with autosomal
      dominant intermediate CMT and mapped the locus on chromosome 10q. Analysis of key
      recombinants maps the gene for autosomal dominant intermediate CMT to a 10.7-Mb
      interval on chromosome 10q24.1-q25.1, between simple tandem repeat markers
      D10S1709 and D10S1795.

PMID- 11533916
TI  - Congenital obstructive uropathy: its origin and contribution to end-stage renal
      disease in children.
AB  - Most children with end-stage renal failure are born with abnormal kidneys, with
      fetal obstructive uropathy accounting for about half these cases. Posterior
      urethral valves (PUV) is overwhelmingly the most common, specific diagnosis, and
      is confined to boys. In general, the condition is sporadic, although familial
      cases have been reported, perhaps suggesting that genetic factors play a role in
      pathogenesis. PUV can present antenatally, detected on routine fetal
      ultrasonography, or postnatally, when it is associated with renal failure and
      bladder dysfunction. Advances in postnatal surgery and medical management have
      reduced the mortality in PUV, but it is uncertain whether antenatal diagnosis or
      treatment (eg, with vesicoamniotic shunts) improves long-term renal outcome.
      Other disorders associated with human fetal obstructive uropathy are urethral
      atresia, the prune belly syndrome, and multicystic dysplastic kidney. The
      nephropathy associated with fetal obstructive uropathy is renal dysplasia and
      comprises undifferentiated and metaplastic tissues. Several studies in animals
      and in humans suggest that fetal urine flow impairment causes deregulation of
      renal precursor cell turnover and expression of growth factor/survival and
      transcription factor genes. Furthermore, some of these morphologic and molecular
      changes can be ameliorated experimentally by fetal surgical decompression or
      administration of specific growth factors.

PMID- 11533917
TI  - Innovative approaches to the preservation of the peritoneal membrane: from bench
      to bedside.
AB  - The functional integrity of the peritoneal membrane is of critical importance for
      the long-term success of peritoneal dialysis therapy. In addition to water and
      solute transport properties, the function of the membrane encompasses complex
      interactions with immune cells, invading microorganisms, and dialysis fluid
      components. During chronic peritoneal dialysis, intraperitoneal homeostasis is
      threatened by the repeated exposure to an unphysiologic environment that is
      created by the instilled solutions. Whereas their acidic pH and hyperosmolality
      were shown to primarily induce alterations of acute cell function, long-term
      peritoneal function might be affected by the repeated exposure to high
      concentrations of glucose and glucose degradation products. In addition to their
      intrinsic toxicity, these might induce or accelerate glycation processes, such as
      formation and deposition of advanced glycation end products in the peritoneal
      membrane. Presently, a new generation of dual-chambered peritoneal dialysis
      solutions combining the advantages of neutral pH and reduced glucose degradation
      products content is being introduced into clinical practice. In addition to an
      improved in vitro biocompatibility profile, emerging clinical trials of these
      novel solutions indicate that they might also improve the host defense status,
      membrane transport characteristics, ultrafiltration capacity, and effluent
      markers of peritoneal membrane integrity, while being safe and effective in
      correcting uremic acidosis and providing relief of inflow pain. Overall, these
      findings suggest that these new dialysis solutions might constitute an important
      step toward better preservation of long-term peritoneal membrane function during
      peritoneal dialysis.

PMID- 11533918
TI  - Hemodialysis in the pediatric patient: state of the art.
AB  - The prevalence of pediatric patients receiving hemodialysis as renal replacement
      therapy has increased over the past decade. Although numerous technologic
      advances have been developed and their impact assessed for adult patients
      receiving hemodialysis, no long-term outcome study currently exists for children
      receiving hemodialysis. Barriers to such study include the necessity for long
      term multicenter participation to enroll enough patients to make definitive
      statements regarding outcome, lack of consensus for an acceptable and practical
      method for hemodialysis adequacy measurement in children, and the need for
      pediatric end-stage renal disease (ESRD)-specific tools for assessment of quality
      of life. The first part of this article reviews issues surrounding hemodialysis
      adequacy measurement in children. In particular, simple but accurate Kt/V and
      normalized protein catabolic rate (nPCR) estimation methods are proposed that
      should allow for more widespread use of Kt/V and nPCR for measurement of urea
      clearance and nutritional status in children receiving hemodialysis, important
      for both patient care and to control for hemodialysis adequacy in pediatric
      outcome studies. In addition, the principles and pediatric study of 2 technologic
      advances, continuous noninvasive monitoring of hematocrit and noninvasive
      ultrasound dilution vascular access flow measurement, are reviewed. Finally,
      suggestions are provided for future study pertinent to both short-term and long
      term outcomes in children receiving hemodialysis.

PMID- 11533915
TI  - Gene conversion and different population histories may explain the contrast
      between polymorphism and linkage disequilibrium levels.
AB  - To characterize linkage disequilibrium (LD) levels in human populations, we have
      analyzed 10 independent noncoding segments in three population samples from the
      major ethnic groups--that is, Africans, Asians, and Europeans. Descriptive
      statistics show that LD decays much faster in the African samples than in the non
      African ones. With the assumption of an equilibrium model, we estimated the
      population crossing-over parameter (4N(e)r(bp), where N(e) is the effective
      population size and r(bp) is the crossing-over rate per generation between
      adjacent base pairs) in the presence of gene conversion. In the African sample,
      LD and polymorphism levels lead to similar estimates of effective population
      size, as expected under an equilibrium model. Conversely, in both non-African
      samples, LD levels suggest a smaller effective population size than that implied
      by polymorphism levels. This observation is paralleled by significant departures
      from an equilibrium model in the spectrum of allele frequencies of the non
      African samples. Besides ruling out the possibility that non-African populations
      are at equilibrium, these results suggest different demographic history (temporal
      and spatial) of these groups. Interestingly, the African sample fits the
      expectations of an equilibrium model based on polymorphism and divergence levels
      and on frequency spectrum. For this sample, the estimated ratio of gene
      conversion to crossing-over rates is 7.3 for a mean tract length of 500 bp,
      suggesting that gene conversion may be more frequent than previously thought.
      These findings imply that disease-association studies will require a much denser
      map of polymorphic sites in African than in non-African populations.

PMID- 11533919
TI  - Risk factors for cardiovascular disease in children on maintenance dialysis.
AB  - Cardiovascular disease mortality is high in children on maintenance dialysis,
      accounting for about 25% of patient deaths. Cardiovascular-related mortality
      rates for children on dialysis are higher than for children with successful
      kidney transplants. Data on the long-term consequences of risk factors for
      cardiovascular disease are lacking for pediatric end-stage renal disease
      patients. This article reviews pediatric data pertaining to the following risk
      factors: anemia, hypertension, hyperlipidemia, left ventricular hypertrophy,
      abnormal calcium-phosphorus metabolism, and hyperhomocysteinemia. The potential
      relationship of end-stage renal disease to the etiology of several functional
      disorders of the cardiovascular system is discussed. Clinical studies are needed
      to assess the prevalence of cardiovascular disease and of cardiovascular disease
      risk factors in the pediatric end-stage renal disease population. Possible
      preventive and therapeutic guidelines need to be developed for at-risk children
      on maintenance dialysis.

PMID- 11533920
TI  - Preservation of bone mass in pediatric dialysis and transplant patients.
AB  - Renal osteodystrophy continues to be a major challenge to the physician treating
      the child with end-stage renal disease (ESRD). The gold standard for the
      assessment of bone status is bone histomorphometry, which divides bone pathology
      into 3 main types; high-turnover, low-turnover, and mixed disease. The high
      turnover disease, related to hyperparathyroidism, has been the one most
      extensively investigated; however, optimal therapy, especially in the growing
      child, is yet unclear. Overzealous treatment might result in adynamic bone
      disease (an extreme example of low-turnover disease), and further interference
      with statural growth. Pre-existent bone disease after kidney transplantation
      seems to worsen immediately, probably because of the high dose of corticosteroids
      used. In children who attain normal kidney function in the allograft, bone status
      seems to improve over time. Little is known about bone in transplanted patients
      with reduced glomerular filtration rate (GFR). The correlation between bone
      histology and its main surrogates, bone remodeling markers and bone mineral
      density, is yet unclear, but it might serve to follow the progress of an
      individual patient. New therapeutic modalities aimed at suppressing
      hyperparathyroidism, and consequently bone resorption, as well as agents directly
      attenuating bone resorption, should be further investigated for their effect on
      bone in patients with ESRD or after transplantation. Similarly, agents
      stimulating bone formation, particularly growth hormone, require further
      attention for their potential to improve bone status. Bone health and the child's
      somatic growth at ESRD or after kidney transplantation are closely related, and
      therapy should be aimed at achieving optimal results for both.

PMID- 11533921
TI  - The impact of dialysis and transplantation on children.
AB  - Effective methods to treat end stage renal disease (ESRD) in children have become
      available in the United States during the last 3 decades. Since the United States
      Congress created the Medicare ESRD Program in 1972, most children with ESRD have
      the option of Medicare insurance. Medicare expenditures for children with ESRD
      range from $14,000 for transplant recipients to $43,000 for dialysis patients per
      year. The tremendous expense of ESRD treatment has led to research to determine
      which treatment options are associated with the best health outcomes and the best
      value (quality/cost) for the money spent treating ESRD. The National Kidney
      Foundation's Dialysis Outcomes Quality Initiative recommends the use of quality
      of life and health status measures to gauge the impact of renal replacement
      therapy on quality of life in the ESRD population. In adult patients with renal
      failure, several generic and disease-specific quality of life measures have been
      validated and tested for reliability. In contrast, little research using
      validated and reliable health status measures has been performed in pediatric
      patients to measure the impact of ESRD. This article summarizes existing
      literature on how we currently measure the impact of dialysis and transplantation
      on children, discusses existing health status measures for children and
      adolescents, and describes how these measures might be used to improve our care
      of patients and long-term outcomes for children with kidney failure.

PMID- 11533922
TI  - The optimal approach to the patient with oxalosis.
AB  - There are many challenges in oxalosis, including prompt, clinical recognition of
      this inborn error of metabolism, management of its many medical problems,
      provision of adequate care at end-stage kidney disease, and optimizing both the
      timing and results of liver and kidney allografts. This review provides a
      framework for the interested clinician to understand the many problems, and to
      begin to assimilate knowledge about an increasingly recognized, metabolic
      disorder. It ends with potential, innovative therapies that are not yet at the
      patient's bedside.

PMID- 11533923
TI  - Myocardial contrast echocardiography: basic principles.
AB  - Myocardial contrast echocardiography (MCE) is a new technique that can be used to
      examine the myocardial microcirculation. It uses gas-filled microbubbles that
      behave similarly to red blood cells in the microcirculation. This report
      describes the parts of the coronary microcirculation visualized by MCE. It also
      describes the types of microbubbles currently available for research. The
      properties of microbubbles and their interaction with ultrasound are also
      described as well as different imaging techniques. This information is necessary
      to understand the basics of MCE.

PMID- 11533924
TI  - Targeted ultrasonic contrast agents for molecular imaging and therapy.
AB  - Targeted contrast agents are expanding the detectability and diagnosis of
      pathology from a strict anatomic to biochemical basis. Moreover, these new
      agents, in their various forms, offer the potential for site-specific drug and
      gene delivery, ie, the "magic bullet" first postulated by Paul Erhlich 100 years
      ago. The ability to direct drugs to the molecular signatures of disease, to
      confirm noninvasively their presence at the site-of-interest, and to quantify the
      adequacy of local drug concentration at the time of treatment, ie, rational
      targeted drug delivery, offers exciting new clinical paradigms in the near
      future.

PMID- 11533925
TI  - Myocardial contrast agents: recent advances and future directions.
AB  - The assessment of perfusion by myocardial contrast echocardiography has evolved
      from the early contrast agents, including agitated saline solutions and hydrogen
      peroxide, to the current second-generation contrast agents. Unlike the first
      generation contrast agents, which are composed of air, the newer, second
      generation agents contain gases with a higher molecular weight and less
      solubility and diffusivity, improving microbubble persistence. The newer contrast
      agents are capable of transpulmonary passage and opacification of the left-heart
      chambers and the myocardial microcirculation after intravenous administration.
      Also, innovative imaging techniques using harmonics and triggered imaging have
      minimized tissue signal and improved signal-to-noise ratio, making the assessment
      of myocardial perfusion possible. Currently, microbubbles are being designed for
      specific research or clinical use by exploiting certain characteristics of the
      microbubble such as the shell, surface characteristics, and/or gas content. Some
      novel applications of microbubble technology include tissue-targeted gene
      therapy, drug delivery, ultrasound-enhanced thrombolysis, and the assessment of
      endothelial function and integrity. This review focuses on the composition,
      physical properties, and acoustic characteristics of the currently available
      myocardial contrast agents and those under clinical investigation. In addition,
      the clinical trials involving these agents will also be discussed.

PMID- 11533926
TI  - Local drug and gene delivery through microbubbles.
AB  - Ultrasound contrast agents (microbubbles) lower the threshold for cavitation by
      ultrasound energy. Ultrasound microbubbles may be used as cavitation nuclei for
      drug and gene delivery. By tailoring the physical properties of microbubbles and
      coating materials, drugs and genetic drugs can be incorporated into ultrasound
      contrast agents. As the microbubbles enter the region of insonation, the
      microbubbles cavitate, locally releasing the therapeutic agents. Cavitation also
      causes a local shockwave that improves cellular uptake of the therapeutic agent.
      As a result of the human genome project and continuing advances in molecular
      biology, many therapeutic genes have been discovered. In the cardiovascular
      system, gene therapy has the potential to improve myocardial vascularization and
      ameliorate congestive heart failure. For successful development of clinical gene
      therapy, however, effective gene delivery vectors are needed. Ultrasound contrast
      agents can be used to develop new, more effective vectors for gene delivery.
      Transthoracic ultrasound can be focused on the heart so that an intravenous
      injection of gene-bearing microbubbles will deliver genes relatively selectively
      to the myocardium. Using this technique, we have produced high levels of
      transgene expression in the insonated region of the myocardium. This new
      technology, using microbubbles and ultrasound for drug and gene delivery, merits
      further study and development.

PMID- 11533927
TI  - An evidence-based review of the resting electrocardiogram as a screening
      technique for heart disease.
AB  - Given renewed interest in the primary prevention of cardiovascular disease, we
      comprehensively reviewed the utility of the electrocardiogram (ECG) for screening
      considering the seminal epidemiologic studies. It appears that conventional risk
      factors relate to long-term risk, while ECG abnormalities are better predictors
      of short-term risk. For individual ECG abnormalities as well as for pooled
      categories of ECG abnormalities, the sensitivity of the ECG for future events was
      too low for it to be practical as a screening tool. This almost certainly relates
      to the low prevalence of these abnormalities. However, all ECG abnormalities
      increase with age and pre-test risk. Also screening with the ECG is of minimal
      cost and likely to decrease further as stand-alone machines are replaced by
      integration into personal computers (PC). Another potential impact on performing
      screening ECGs would be distribution and availability of digitized ECG data via
      the World Wide Web. For clinical utility of ECG data, comparison with previous
      ECGs can be critical but is currently limited. PC based ECG systems could very
      easily replace many of the ECG machines in use that only have paper output. PC
      ECG systems would also permit interaction with computerized medical information
      systems, facilitate emailing and faxing of ECGs as well as storage at a
      centralized web-server. Web-enabled ECG recorders similar to the new generation
      of home appliances could follow this quick PC solution. A serious goal for the
      medical industry should be to end the morass of proprietary ECG digital formats
      and follow a standardized format. This could lead to a network of web-servers
      from which every patient's ECGs would be available. Such a situation could have a
      dramatic effect on the advisability of performing screening ECGs.

PMID- 11533928
TI  - The effects of heparin and oral anticoagulants on thrombus propagation and
      prevention of the postphlebitic syndrome: a critical review of the literature.
AB  - Based on a comprehensive literature search, this report aims to examine the
      effects of heparin and oral anticoagulants on thrombus propagation and prevention
      of the postphlebitic syndrome. The effects on recurrence of thromboembolic
      disease have not been addressed. It is concluded that published reports of serial
      venograms and ultrasound examinations of patients treated with conventional
      anticoagulant therapy for deep venous thrombosis show either no change or
      thrombus extension in the first few months in approximately 50% of cases.
      Approximately two thirds of patients will have damage to the venous valves,
      leading to incompetence or other hemodynamic changes. More than one third of
      patients so treated may have oedema, leg pain, or other severe symptoms on long
      term follow-up. The consistency with which these outcomes have been observed,
      particularly in many large, recent, prospective trials, adds to the credibility
      of these figures. The results of prospective controlled trials have failed
      uniformly to show any significant local benefits of anticoagulant therapy for
      deep vein thrombosis compared with other treatments or placebo. There does not
      seem to be any convincing evidence that heparin exerts a favorable influence on
      pulmonary embolism in situ or on portal vein thrombosis. Use of anticoagulant
      therapy to limit thrombus propagation therefore cannot be said to be "evidence
      based." These generally poor outcomes with regard to postphlebitic complications
      should lead to an active exploration of alternative methods of management.
      Substantial uncertainties surrounding many fundamental aspects of the treatment
      of this disease remain, and further placebo-controlled trials are needed.

PMID- 11533929
TI  - Porters of the eastern hills of Nepal: Body size and load weight.
AB  - This study documents the activities of 635 porters transporting goods along three
      traditional trade routes of eastern Nepal. Nearly 95% of the porters were male.
      They ranged in age from 10-65 years, and most of them had begun to perform long
      distance portage at 12-15 years of age. Mean body mass and height of adult males
      in the combined sample (n = 438) was 49.7 +/- 5.0 kg and 155.5 +/- 6.5 cm,
      respectively. Adult males age 20-49 years carried loads of 73 +/- 15 kg,
      equivalent to 146% +/- 30% of body mass. Body size of adult males was not a
      strong predictor of load weight. The correlation between body mass and load was r
      = 0.24 (P < 0.0001), and between height and load was r = 0.16 (P < 0.001).
      Another significant determinant of load weight was whether the load was carried
      for profit or for domestic use. The most reasonable explanation for the ability
      of Nepali porters to carry such large loads in spite of their small body size is
      the ability to pace themselves by making frequent rest stops. Heart rate
      monitoring of 26 adult male commercial porters demonstrated how porters regulate
      heart rate and energy expenditure by resting the load every two to three minutes
      on the T-headed walking stick (tokma) and by setting the load periodically on
      load-resting platforms (chautaras) for longer recovery periods. Am. J. Hum. Biol.
      11:1-11, 1999. Copyright 1999 Wiley-Liss, Inc.

PMID- 11533930
TI  - Analysis of the velocity curve for height by the wavelet interpolation method in
      children classified by maturity rate.
AB  - The Wavelet Interpolation Method (WIM) developed by Meyer ([1992] Wavelets and
      Operators. Cambridge: Cambridge University Press) has been proposed as an
      analytical method for the accurate description of longitudinal growth velocity in
      height and identification of the age at maximum peak velocity (MPV) in the curve.
      The distance curve in height was determined by interpolating the longitudinal
      records of 98 boys and 88 girls, 6-17 years old, with the WIM. The distance curve
      was then differentiated to obtain a velocity curve. Age at MPV estimated from the
      velocity curve was utilized as a criterion of maturity rate (timing), and five
      maturity groups (early, little early, average, little late and late) were defined
      in both sexes. Four type models were derived from the occurrence of secondary
      peaks (mid-growth spurt and after-growth spurt): type model A, appearance of a
      mid-growth spurt and MPV; type model B, appearance of an after-growth spurt and
      MPV; type model C, appearance of a mid-growth spurt, an after-growth spurt and
      MPV; and type model D, appearance of MPV only. The individual growth data of boys
      and girls classified by maturity rate were sorted into the four type models. The
      frequency of occurrence of the four type models in groups classified by maturity
      rate was then analyzed, and the characteristics of height growth velocity was
      examined in boys and girls. Am. J. Hum. Biol. 11:13-30, 1999. Copyright 1999
      Wiley-Liss, Inc.

PMID- 11533931
TI  - Comparative analysis of age prediction by markers of bone change in the hand
      assessed by roentgenography.
AB  - The major aim of this study was to develop an accurate method of age prediction
      for a wide range of ages based on the roentgenographic assessment of the hand
      bones. Such a method may be of particular interest in paleoanthropology and
      forensic medicine. The present paper provides the results of an analysis of
      individuals belonging to two ethnically different population samples: 1) Chuvasha
      (the Russian Federation), 293 males and 254 females, aged 18-91 and 18-86 years,
      respectively; and 2) Turkmenians (the Republic of Turkmenia), 257 males and 386
      females, aged 18-82 and 17-83 years, respectively. The hands of study
      participants were roentgenographed with standard methodology. For each
      roentgenogram an equidistant osseographic score (OSS) including the descriptive
      criteria of bone age was estimated. In addition, an osteoarthritic and an
      osteoporotic score (OA and OP, respectively) were assigned to each individual. OA
      was a modification of the Kellgren/Lawrence scale, whereas the OP was locally
      developed. Results of the multiple logistic regression analysis clearly indicated
      that OSS is a strong predictor variable of an individual's age, with R reaching
      0.93 in Chuvasha and 0.89 in Turkmenians (P < 0.001). The standard errors of
      estimate were approximately +/-5-7 years and compared favorably with most known
      methods of age assessment using bones. This study provides an efficient method of
      age prediction, with acceptable accuracy, and extends the upper limit of
      prediction to the age of 70 years. An additional finding of interest was the
      coexistence of OA and OP in the bones of the same hand. The observed correlation
      between these two conditions reached 0.8 (P < 0.001). Am. J. Hum. Biol. 11:31-43,
      1999. Copyright 1999 Wiley-Liss, Inc.

PMID- 11533932
TI  - Superoxide dismutase activity levels in a Spanish population 50-93 years.
AB  - Reports dealing with the free radical theory of aging have focused on the
      possibility that aging may be accelerated in elderly individuals due to lowering
      of antioxidant defenses. Accordingly, free radical processes involving oxygen
      continously damage cells and tissues in the body, leading to degeneration and
      aging. Scavenging enzymes represent one of the several natural defense mechanisms
      against free radical-induced damage. These enzymes include superoxide dismutase.
      To investigate the role of this enzyme in aging, its activity was measured in 126
      individuals 50-93 years of age. Cu/Zn superoxide dismutase (SOD(1)) was measured
      in red blood cells using the Minami and Yoshikawa method. The results were
      compared with those observed in a population between 18 and 65 years of age.
      SOD(1) activity in males remains constant or slightly decreases with age, whereas
      in females SOD(1) activity shows a significant increase in individuals between 68
      and 93 years. Am. J. Hum. Biol. 11:45-47, 1999. Copyright 1999 Wiley-Liss, Inc.

PMID- 11533933
TI  - Culture, skin color, and arterial blood pressure in Brazil.
AB  - Populations of African descent in North and South America have higher mean blood
      pressures and higher rates of hypertension than populations of European descent
      or populations in Africa. Within populations of African descent, darker skinned
      persons have higher blood pressures than lighter skinned persons. Whether
      examined within or between populations, there is an interaction between skin
      color and socioeconomic status (SES) in relation to blood pressure, with persons
      with dark skin color and low SES having the highest blood pressures. This
      interaction was examined in Brazil using a measure of a cultural dimension of SES
      called "cultural consonance in lifestyle." This measure was derived using
      cultural consensus analysis linked with social survey data. It was found that
      darker skinned Brazilians with lower cultural consonance in lifestyle had
      adjusted systolic blood pressures 16.2 mm Hg higher than darker skinned
      Brazilians with higher cultural consonance (P <.01); the corresponding difference
      in adjusted diastolic blood pressure was 9.7 mm Hg (P <.04). The differences for
      lighter skinned Brazilians were 6.4 mm Hg (P <.02) and 1.0 mm Hg (not
      significant), respectively. These results could be due either to an interaction
      of genetic predisposition and SES, or the result of a socially and culturally
      mediated process. Given that cultural consonance in lifestyle measures the
      ability of the person to live up to cultural norms, and given the existence of
      racial stratification in Brazil, it is argued that a social and cultural
      mediation of the relationship is more plausible. Am. J. Hum. Biol. 11:49-59,
      1999. Copyright 1999 Wiley-Liss, Inc.

PMID- 11533934
TI  - Comparison of two techniques for measurement of visceral adipose tissue cross
      sectional areas by computed tomography.
AB  - Most computed tomography (CT) scanners used today are able to accurately measure
      adipose tissue (AT) areas at any site of the body. However, first generation CT
      scanners used by some medical centers are not equipped with appropriate software
      allowing the measurements of AT areas. The aim of this study was to validate a
      technique of AT area measurements independent from CT scanner software. Abdominal
      AT areas were recorded with CT in a sample of 30 men. Areas were thereafter
      calculated using the standard CT software technique. Total and visceral AT areas
      were then remeasured using another technique for which X-ray film of each
      subject's scan was analysed by a system completely independent from the CT
      scanner (imaging densitometer and NIH image analysis software). Correlations
      between measurements obtained with the two techniques were very strong for both
      total (n = 0.99; SEE = 11.7 cm(2)) and visceral AT areas (r = 0.99; SEE = 5.3
      cm(2)). Values obtained with the image analysis method were generally higher than
      with the conventional CT software technique (cross-sectional areas of AT were
      overestimated by 4.7% for total abdominal and 8.5% for visceral AT respectively).
      In conclusion, the results indicate that measurements obtained with this image
      analysis technique would be adequate to correctly rank subjects according to
      levels of total or visceral AT areas. However, since this method appears to
      slightly overestimate AT areas, a standardized correction should be performed
      before comparing subjects with AT areas measured with this technique to subjects
      whose AT areas have been obtained with the conventional CT software technique.
      Am. J. Hum. Biol. 11:61-68, 1999. Copyright 1999 Wiley-Liss, Inc.

PMID- 11533935
TI  - Body measurement variability, fatness, and fat-free mass in children 8, 11, and
      14 years of age: Project HeartBeat!
AB  - Project HeartBeat! is a four year mixed-longitudinal study of the development of
      cardiovascular risk factors in White and African American children who at
      baseline comprised three age cohorts 8, 11, and 14 years. This paper focuses on
      the anthropometric variables which were chosen to reflect body fat and fat-free
      mass. Selected anthropometric dimensions are compared with those of samples from
      the combined National Health and Nutrition Examination Surveys I and II to
      explore the similarities of the samples in terms of central tendencies and
      variances. The measurements were then explored in terms of their ability to
      estimate the two compartment model of body composition: fat-free mass (FFM) and
      body fat (BF) from bioelectrical impedance (BIA). Project HeartBeat! children are
      slightly larger than NHANES children and have variances that are generally
      comparable to the national surveys. Over seven percent (7.7%) of children were
      overweight (BMI) and 25% had 'mild obesity' by %BF. Three different factor
      analytic methods (incomplete principal components, alpha and maximum likelihood)
      produced two latent variables from 17 anthropometric dimensions which together
      accounted for 76-83% of the variation: (1) A body mass factor (F1) which was
      weighted highly on six circumferences, weight and six skinfolds, and (2) a linear
      growth factor (F2) which was strongly associated with height, arm length, and
      sitting height. Triceps, subscapular and midaxillary skinfolds were consistently
      highly loaded on the body mass factor and their sum was highly correlated to %BF
      and fat mass (0.90-0.99). This suggests that this sum could be used to estimate
      fatness in children in studies where the BIA or other body composition techniques
      are unavailable. FFM and %BF were predicted from the anthropometric factors. Both
      factors contributed to the estimate of FFM (R(2) = 0.81-0.93), although F2
      contributed proportionately more. The 'body mass' factor (F1) was the main
      predictor of %BF (R(2) = 0.86-0.93), though at some ages the linear factor (F2)
      was significantly and negatively related to %BF. This set of anthropometric
      dimensions, taken for the purpose of estimating body composition and summarized
      as two latent vectors by factor analysis, strongly reflects body fat and FFM in
      children and adolescents. Am. J. Hum. Biol. 11:69-78, 1999. Copyright 1999 Wiley
      Liss, Inc.

PMID- 11533937
TI  - Progress in human body composition research.

PMID- 11533936
TI  - Program of the 24th Annual Meeting of the Human Biology Association.

PMID- 11533938
TI  - Human biology: From a love to profession and back again.
AB  - In 1937-1939, while working with my right hand as psychologist in the Bata Shoe
      Co. in Zlin, Moravia, with my left hand I was involved in research on age changes
      in body dimensions and profited from the interdisciplinary orientation of the
      (Czech) Biotypological Society, of which I was an active member. In 1941 I joined
      the Laboratory of Physiological Hygiene, a research and teaching unit in the
      School of Public Health of the University of Minnesota. My contributions ranged
      from philosophy of science through a broadly conceived physical anthropology,
      including nutritional anthropometry, to the study of behavior. I did field work
      both in Yugoslavia and in the United States. The research topics included aging,
      the effects of smoking, and etiology of coronary heart disease. In the
      collaborative monograph on The Biology of Human Starvation, I co-authored
      chapters on body weight, physical appearance and external dimension, body fat, a
      synthesizing chapter on compartments of the body, special senses, neuromuscular
      functions and motor performance, and seven chapters devoted to psychology. Am. J.
      Hum. Biol. 11:143-155, 1999. Copyright 1999 Wiley-Liss, Inc.

PMID- 11533939
TI  - History of the study of human body composition: A brief review.
AB  - This review assembles a chronology of human body composition research with the
      goal of exposing historical roots and identifying future potential trends. Body
      composition research has emerged over the past several decades as a distinct
      field, and for many scientists body composition is their primary investigative
      focus. Technological advances will likely move the field forward and, ultimately,
      help to expand knowledge of human body composition variability in health and
      disease. Am. J. Hum. Biol. 11:157-165, 1999. Copyright 1999 Wiley-Liss, Inc.

PMID- 11533940
TI  - Human body composition: A review of adult dissection data.
AB  - Although body composition analysis is popular, dissection data are sparse and
      sometimes difficult to access. Published data that include the weights of skin,
      adipose tissue, muscle, and bone, along with body weight, are reviewed. The 31
      men and 20 women include 34 cadavers from three separate dissection studies in
      Brussels, 12 from 19th century reports, and 5 from the United States. The age
      range was 16-94y. Men differed from women in that they had less adipose tissue
      and more muscle in both absolute and relative terms. The body mass index (BMI)
      did not differ between the sexes, because lower weights of muscle and bone
      compensated for the greater adiposity in women. The relationship between the BMI
      and relative adiposity was significant, but the BMI explained only about one
      third of the variance in adiposity, indicating that in this sample it is a poor
      predictor of fatness. The composition of the fat-free weight (FFW) and adipose
      tissue free weight (ATFW), though less variable than body weight, showed enough
      variability that the assumption of constancy of the fat-free body required for
      densitometry and other indirect methods of fat estimation, could not be
      supported. In the few dissections that did fat extraction, essential on non
      adipose fat, varied from 4-14% of the FFW, thus undermining the concept of lean
      body weight. More dissection data are needed, especially in children and
      adolescents, and especially in conjunction with in vivo body composition methods
      to help in their validation. Am. J. Hum. Biol. 11:167-174, 1999. Copyright 1999
      Wiley-Liss, Inc.

PMID- 11533942
TI  - Fat distribution during childhood and adolescence: Implications for later health
      outcomes.

PMID- 11533941
TI  - Critical appraisal of the estimation of body composition via two-, three-, and
      four-compartment models.
AB  - This review explores the robustness of the assumptions underpinning the two- (fat
      mass [FM], fat-free mass [FFM]), three- (FM; total body water [TBW], fat free dry
      solid), and four- (FM; TBW; bone mineral [BM], residual) compartment models of
      body composition. The measurement of body density (BD) via underwater weighing
      (UWW) and TBW via isotopic dilution are the two most frequently used two
      compartment techniques. The former assumes that the FM and FFM have densities of
      0.9007 g/cm(3) and 1.1000 g/cm(3), respectively, while the latter uses a FFM
      hydration constant. Although both techniques can estimate body composition
      precisely (technical error of measurement [TEM]: UWW = 0.4 %BF; TBW = 0.6 %BF),
      the validity of these estimates is adversely affected by biological variability
      in the assumed percentages for the FFM components (TBW = 73.72%; protein =
      19.41%; BM = 5.63%; non-BM = 1.24%). The three-compartment model, which
      incorporates measures of BD and TBW, greatly increases validity by removing
      errors relating to variability in TBW, which comprises the largest percentage of
      the FFM and is furthermore acutely variable. The four-compartment model
      marginally improves on the three-compartment model by additionally controlling
      for BM, which displays less variability than the TBW component of the FFM. The
      three- and four-compartment models therefore provide more valid estimates of body
      composition than the two-compartment model, and this increased accuracy is not
      offset by propagation of errors (TEM = 0.7 %BF for both models) from the
      combinations of multiple measurements (BD, TBW, BM). Am. J. Hum. Biol. 11:175
      185, 1999. Copyright 1999 Wiley-Liss, Inc.

PMID- 11533943
TI  - Variation in subcutaneous adipose tissue distribution associated with age, sex,
      and maturation.
AB  - Age-, sex-, and maturity-associated variation in subcutaneous adipose tissue
      (SAT) distribution is reviewed and then considered longitudinally in a sample of
      Polish youth. Current study of adipose tissue distribution places considerable
      emphasis on abdominal adiposity, specifically intra-abdominal or visceral adipose
      tissue (VAT). Most studies of children and adolescents do not include an
      abdominal skinfold, and when it is available, the skinfold is grouped with others
      as a sum of skinfolds. Correlations between abdominal VAT and SAT based on
      computerized tomography in non-obese children are moderate to high, and those
      between the suprailiac and abdominal skinfolds and abdominal VAT are moderately
      high. Changes in three individual skinfolds (triceps, subscapular, abdominal) and
      ratios of the skinfolds were considered by chronological age and relative to the
      timing of peak height velocity (PHV), and in children of contrasting maturity
      status in participants of the Wroclaw Growth Study, 193 boys and 197 girls, who
      were followed longitudinally from 8 to 18 years of age. Individual skinfolds
      behave differently during childhood and adolescence, and the changes are
      influenced by the timing of the adolescent growth spurt. Sex differences in
      estimated velocities are negligible up to about 2 years before PHV; then
      velocities tend to be higher in girls. The velocity of the triceps skinfold is
      negative in boys just before and after PHV; estimated velocities for the trunk
      skinfolds are positive through the growth spurt in both sexes, and are somewhat
      greater after PHV, especially in girls. The individuality of changes in
      individual skinfolds during the adolescent spurt contributes to changes in the
      relative distribution of SAT at this time. The timing of the adolescent growth
      spurt is an important factor influencing the distribution of SAT both in the
      total sample and in youth classified as early and late maturing. Am. J. Hum.
      Biol. 11:189-200, 1999. Copyright 1999 Wiley-Liss, Inc.

PMID- 11533944
TI  - Visceral fat in prepubertal children: Influence of obesity, anthropometry,
      ethnicity, gender, diet, and growth.
AB  - Visceral fat, or intra-abdominal adipose tissue (IAAT) lies deep within the
      abdominal cavity and can only be directly quantified with imaging techniques.
      IAAT has been detected in children as young as 5 years of age. IAAT generally
      increases in proportion with general fatness, but the relationship between IAAT
      and total body fat is complex; in children, a major portion of the variance in
      IAAT is independent of total body fat. The waist-to-hip ratio and the
      trunk:extremity skinfold ratio are not good indices of IAAT in children, and
      central skinfolds and waist circumference alone are highly correlated with IAAT
      as well as subcutaneous abdominal adipose tissue (r = 0.85-0.92). African
      American children have less IAAT than Caucasian children, and gender differences
      in IAAT become more apparent after adolescence. Preliminary evidence in children
      suggests that IAAT may have a stronger influence on cardiovascular risk factors
      than dietary fat intake. Preliminary evidence in children also suggests that
      acquisition of IAAT during growth is a linear process that occurs in proportion
      to general increases in body fat. The study of the regulation of IAAT acquisition
      during childhood development and its relationship with long-term disease risk is
      in its early infancy and further studies are required. Am. J. Hum. Biol. 11:201
      207, 1999. Copyright 1999 Wiley-Liss, Inc.

PMID- 11533945
TI  - Hormonal changes during puberty and their relationship to fat distribution.
AB  - In adults, abdominal visceral adiposity is related to an increased risk of
      cardiovascular diseases, Type 2 diabetes mellitus, and stroke. The antecedents of
      these conditions likely begin with the alterations in body fat distribution
      during childhood and adolescence. The sexually dimorphic alterations in fat
      distribution are influenced by sex differences in hormone concentrations,
      anatomical differences in the number and density of specific hormone receptors,
      capillary blood flow, and the activity of enzymes promoting lipid synthesis or
      degradation. Hormones influencing the amount and regional distribution of adipose
      tissue during puberty include cortisol, insulin, growth hormone, and the sex
      steroids. Cortisol and insulin promote fat deposition while the sex steroids and
      GH stimulate lipolysis. An overly sensitive hypothalamic-pituitary-adrenal axis
      may exist in obesity and disrupt the balance between the lipogenic effects of
      cortisol and insulin and the lipolytic effects of sex steroids and growth
      hormone. Leptin is released from the adipocytes and may act as a metabolic signal
      to the hypothalamic areas controlling satiety, energy expenditure, and the
      regulation of cortisol, insulin, sex steroid and growth hormone release. The
      complex issues of the hormonal control of alterations in body fat distribution
      during puberty are developed and a working model is proposed. Am. J. Hum. Biol.
      11:209-224, 1999. Copyright 1999 Wiley-Liss, Inc.

PMID- 11533946
TI  - Genetics of abdominal visceral fat levels.
AB  - The purpose of this review is to explore the evidence accumulated thus far that
      suggests a genetic component to the observed variation in abdominal visceral fat
      (AVF) levels. The precise determination of AVF levels in humans is limited to
      methods such as computerized tomography and magnetic resonance imaging; thus, few
      studies have examined the role of genetic factors on this phenotype. Evidence
      from the Quebec Family Study (QFS) and the HERITAGE Family Study indicates that
      between 50-55% of the variance in AVF levels, adjusted for total fatness, is
      attributable to genetic factors. Additionally, a major gene hypothesis for AVF
      was supported in the both the QFS and HERITAGE Family Study. However, after
      adjustment for total fat mass the support for a major gene was reduced,
      suggesting that a major gene which affects fat mass may also affect AVF either
      directly (pleiotropy), or indirectly. The search for candidate genes that may
      impact AVF levels is in its infancy, and few candidate genes have been
      identified. However, the glucocorticoid receptor (GRL), ss3 adrenergic receptor
      (ADRB3), and fatty acid binding protein 2 (FABP2) genes have been significantly
      associated with AVF or intra-abdominal fat levels in humans. In addition, three
      quantitative trait loci obtained from crosses of mice, the Do2, Mob4, and Qbw1
      loci have been linked with mesenteric or abdominal fat and are thus considered
      positional candidate genes for AVF levels. The search for candidate genes or
      random genetic markers associated with AVF levels is a challenging prospect.
      However, given the significant heritability of this phenotype, the quest remains
      promising. Am. J. Hum. Biol. 11:225-235, 1999. Copyright 1999 Wiley-Liss, Inc.

PMID- 11533947
TI  - Role of exercise intervention in improving body fat distribution and risk profile
      in children.
AB  - The influence of 4 months of physical training (PT) and detraining on body
      composition, and risk factors for coronary artery disease (CAD) and noninsulin
      dependent diabetes mellitus (NIDDM) was examined. The subjects were 81 obese 7-11
      year-olds. At baseline, visceral adipose tissue (VAT) was the main adiposity
      variable cross-sectionally associated with unfavorable levels of the lipid
      lipoprotein risk factors, while fat mass was more highly correlated with insulin,
      systolic blood pressure, and leptin. Adiposity measures were associated with
      unfavorable concentrations of clotting-fibrinolysis factors. Subjects were
      randomly assigned to engage in PT for the first or second 4-month period of the
      study; for most variables, tests were done at 0, 4, and 8-month time points. The
      PT program was offered 5 days a week for 40 min/session. For the 73 children who
      completed 4 months of PT, attendance was 80% and heart rate during the sessions
      was 157 bpm. PT had a favorable influence on percent fat, VAT, subcutaneous
      abdominal adipose tissue, insulin, triacylglycerol, and cardiac parasympathetic
      activity. Detraining generally led to unfavorable changes in percent fat and
      associated risk factors. Leptin decreased during periods of PT and increased
      following cessation of PT. No significant changes due to PT were found for diet,
      hemodynamic, left ventricular, or most lipid parameters. Thus, 4 months of
      controlled PT, without dietary intervention, had a favorable impact on body
      composition and some obesity-associated CAD/NIDDM risk factors. Am. J. Hum. Biol.
      11:237-247, 1999. Copyright 1999 Wiley-Liss, Inc.

PMID- 11533948
TI  - Syndrome X in children: Influence of ethnicity and visceral fat.
AB  - Syndrome X, the clustering of risk factors for cardiovascular disease, is
      recognized as an obesity-related health concern among adults. In particular,
      individuals with visceral (intra-abdominal) obesity are prone to developing
      syndrome X. Although extremes of visceral fat have been detected in prepubertal
      children, the extent to which visceral fat contributes to the development of
      disease risk factors in children is not known. This review addresses the
      occurrence of syndrome X and its antecedents in the pediatric population, as well
      as two specific issues regarding syndrome X in children: the roles of ethnicity
      and visceral fat. The central feature to emerge from most studies is that basal
      and post-challenge insulin are significantly higher in African-American, Mexican
      American, and Pima Indian children compared to Caucasian children. Although these
      ethnic differences are independent of adiposity, adiposity is associated with
      greater insulin in all ethnic groups examined. Mexican-Americans have a higher
      lipid risk factor level, which is related to greater obesity, and African
      Americans have lesser lipid-associated risk, independent of obesity. African
      American children may be more likely to develop type 2 diabetes due to obesity
      independent hyperinsulinemia and insulin resistance, but appear less predisposed
      to the obesity-related clustering of risk factors associated with syndrome X.
      Mexican-American children may be more likely to develop syndrome X due to greater
      obesity-related hyperinsulinemia and dyslipidemia. Total body fat, rather than
      visceral fat, appears be the primary determinant of insulin resistance prior to
      puberty. However, visceral adipose tissue is uniquely related to both insulin and
      lipid risk factors in children and adolescents, and thus may contribute to the
      development of the early stages of syndrome X. Am. J. Hum. Biol. 11:249-257,
      1999. Copyright 1999 Wiley-Liss, Inc.

PMID- 11533949
TI  - Relationship between abdominal visceral fat and metabolic risk factors in obese
      adolescents.
AB  - The distribution of body fat may play an important role in determining the risk
      of obesity-related morbidity in obese adults. In view of the alarming increase in
      adolescent obesity, this article addresses whether defects in insulin action and
      secretion and increased intra-abdominal fat that typify central obesity in adults
      are expressed early in the course of developing obesity. The euglycemic
      hyperinsulinemic clamp technique with stable isotopes was used to determine
      insulin effects on glucose and glycerol turnover in obese and lean adolescents.
      The hyperglycemic clamp was used to quantitate insulin secretion, while magnetic
      resonance imaging was used to directly assess abdominal subcutaneous and visceral
      fat. The results indicate that obese adolescent girls have the following
      characteristics: 1) insulin resistance with major defects in oxidative and
      nonoxidative glucose metabolism; 2) hyperinsulinemia in the fasting state and in
      response to intravenous glucose; and 3) impaired suppression of total body lipid
      oxidation and plasma FFA concentrations in response to insulin. Am. J. Hum. Biol.
      11:259-266, 1999. Copyright 1999 Wiley-Liss, Inc.

PMID- 11533950
TI  - Adolescent spurts in body dimensions: Average and modal sequences.
AB  - The sequence of growth spurts in 11 body dimensions was examined in 101 Polish
      adolescents, 52 males and 49 females, followed longitudinally from 11-18 years.
      The dimensions included weight; stature; symphyseal height; biacromial and
      bicristal breadths; and arm, forearm, chest, thigh and calf circumferences. Upper
      segment length was estimated as stature minus symphyseal height. Measurements
      were taken quarterly from 11-14 years, and annually or less frequently
      thereafter. Growth curves were fitted to individual longitudinal observations
      using kernel regression to derive estimates of ages at peak velocity (PV) and
      peak velocities. Within each sex, mean ages at PV were used to define the average
      sequence, while the most frequently observed sequence of PVs in individuals was
      used to define the modal sequence. Average and modal sequences differed, the
      latter probably reflecting individual variability in timing. The spurt in the
      estimate of leg length (symphyseal height) occurred prior to that for stature in
      males (first in the sequence) and was nearly coincident with that for stature in
      females (second in the sequence by 0.01 years). The timing of spurts in other
      dimensions within each sex was more variable in both average and modal sequences.
      Am. J. Hum. Biol. 11:287-295, 1999. Copyright 1999 Wiley-Liss, Inc.

PMID- 11533951
TI  - An investigation of human apolipoproteins B and E polymorphisms in two African
      populations from Ethiopia and Benin.
AB  - Three polymorphisms (XbaI, EcoRI, and Ins/Del) of the apolipoprotein B (APOB)
      gene and the polymorphism of apolipoprotein E (APOE) were investigated in two
      population samples of Amhara and Oromo origin from Ethiopia, and in two
      population samples of Bariba and Berba origin from Benin. No heterogeneity was
      observed within each major group. The cumulated frequencies of the APOB X+, R+,
      and D alleles for the Ethiopia and the Benin groups were 0.268 and 0.133, 0.958
      and 0.818, 0.206 and 0.223, respectively. Regarding APOE, the cumulated allele
      frequencies of Ethiopia and Benin were 0.031 and 0.103 for epsilon*2 allele,
      0.811 and 0.742 for epsilon*3, and 0.143 and 0.155 for epsilon*4, respectively.
      APOE typing performed at the protein level only in the Ethiopians revealed a
      variant allele, epsilon*5, found at the polymorphic level both in the Amhara and
      in the Oromo (cumulated frequency: 0.015). A tentative explanation for the higher
      frequencies of epsilon*4 and epsilon*5 alleles was sought in relation to the
      lifestyle and ethnicity of the two populations. Am. J. Hum. Biol. 11:297-304,
      1999. Copyright 1999 Wiley-Liss, Inc.

PMID- 11533952
TI  - An analysis of the spatial distribution of surnames in the Lecco area (Lombardy,
      Italy).
AB  - The internal mobility of the population of the province of Lecco (Lombardy,
      Italy) was evaluated on the basis of the frequency of characteristic surnames in
      three territorial areas as a function of their geographical distance. Nearly
      three fourths of the patterns are statistically significant in one of the three
      areas, where the process of diffusion of surnames could be interpreted as due to
      socioeconomic factors. On the contrary, a similar distribution is less evident in
      the other two areas of the same territory. Am. J. Hum. Biol. 11:305-315, 1999.
      Copyright 1999 Wiley-Liss, Inc.

PMID- 11533953
TI  - Modeling the effects of nutritional and socioeconomic factors on the growth and
      morbidity of Kenyan school children.
AB  - This paper estimates dynamic models for the height, head circumference, weight,
      and morbidity of approximately 110 Kenyan school children (6-9 years) in a
      multivariate longitudinal data framework. Dynamic models allow anthropometric
      dimensions to depend on the respective measurements in the previous period. The
      system of 4 equations specified for height, head circumference, weight, and
      morbidity incorporates the inter-relationships among these variables; explanatory
      variables in the model consist of nutritional, socioeconomic, demographic, and
      environmental factors. The model parameters are estimated using the principle of
      maximum-likelihood, while controlling for the unobserved between-children
      differences. The main findings are, first, that calcium intakes are positively
      associated with height while protein and energy intakes are associated with
      weight. Vitamin A intakes are negatively associated with morbidity. Second,
      socioeconomic status plus the cash income of the household is a significant
      predictor of height, head circumference, and morbidity. Third, maternal height is
      positively associated with children's height and maternal body mass index (BMI)
      is positively associated with children's weight. Fourth, parents' scores on
      psychological tests, mother's age, and children's hemoglobin concentration are
      negatively associated with morbidity while mothers' morbidity is positively
      associated with children's morbidity. Implications of the modeling results are
      discussed. Am. J. Hum. Biol. 11:317-326, 1999. Copyright 1999 Wiley-Liss, Inc.

PMID- 11533954
TI  - Discontinuity of life conditions at the transition from the Roman imperial age to
      the early middle ages: Example from central Italy evaluated by pathological dento
      alveolar lesions.
AB  - Teeth are highly informative in the study of past human populations. In
      particular, the occurrence of lesions in the masticatory apparatus relates
      diseases, diet, and living conditions. The dental pathology of three skeletal
      samples from the north-central part of Latium (central Italy) is reported. Two of
      them belong to the Roman Imperial Age (1st-3rd century AD): the first (including
      942 permanent teeth and 1,085 tooth sockets) represents the rural town of Lucus
      Feroniae and is mainly composed of slaves and/or war veterans, whereas the second
      (872 permanent teeth and 1,325 tooth sockets) comes from the Isola Sacra
      necropolis at Portus Romae and represents the "middle class" segment of an urban
      population. The medieval sample (912 teeth and 1,097 tooth sockets), dated to the
      7th century AD, belongs to the Lombard necropolis of La Selvicciola. All of the
      samples were examined for caries, abscesses, antemortem tooth loss, calculus,
      alveolar resorption, attrition, and enamel hypoplasia; standard methods were used
      to identify, classify, and quantify these conditions. The results reveal
      different patterns of dental and alveolar lesions for the three populations,
      indicating a different combination of dietary factors and hygienic conditions in
      the Roman samples compared to the Lombard series. As evidenced by multivariate
      correspondece analysis, the Romans show afffinites between each other, whereas
      the Medieval sample appears associated with the incidence of caries and the
      pathological conditions related to them, thus indicating increase of these
      lesions and deterioration of the quality of life in the transition to the early
      Middle Ages. These data agree with the respective archeological characterizations
      of the necropolises and the hypothetical social composition of each population.
      Am. J. Hum. Biol. 11:327-341. Copyright 1999 Wiley-Liss, Inc.

PMID- 11533955
TI  - Numerical analysis of the proximal humeral outline: Bilateral shape differences.
AB  - A new method is presented for the numerical analysis of bilateral differences in
      the size and shape of the proximal humeral outlines using elliptical Fourier
      functions (EFFs). A skeletal sample of 36 pairs of right and left humeri was
      used. The proximal superior view in the plane of the proximodistal axis of each
      humerus was photographed with an 800 mm telephoto lens. The two-dimensional
      humeral outlines were carefully traced onto acetate sheets and 54 boundary points
      were located. These points were digitized and used to compute size-standardized
      EFFs with 27 harmonics. From the EFFs, a set of expected points on the proximal
      humeral outline was generated using the centroid as an origin. Superimposition of
      the right and left humeral outlines on this centroid provided a detailed picture
      of the relative bilateral shape differences with respect to that center. The
      proximal humeri showed significant bilateral size and shape differences, although
      the pattern of asymmetry in shape varied with respect to the region on the
      boundary outline. In particular, one localized aspect, the tubercular region of
      the proximal humeri showed significant bilateral shape differences. In contrast,
      the humeral head consistently showed not only a much smaller degree of bilateral
      shape differences, but also much less variability in size as well as shape. The
      results suggest that while the overall articular shape changes little with
      altered mechanical loadings placed on articular surfaces, the changes in the
      tubercular regions of the proximal humeri may be susceptible to the varying
      stresses associated with particular physical activities. Am. J. Hum. Biol. 11:343
      357, 1999. Copyright 1999 Wiley-Liss, Inc.

PMID- 11533956
TI  - Albumin genetic variability in South America: Population distribution and
      molecular studies.
AB  - A total of 5,020 individuals living in two southern Brazilian states were
      screened in relation to albumin types; two variants were found, in Passo Fundo
      (Nagasaki 2) and Vera Cruz (Tradate 2). Another variant, detected in the
      northeast, was identified as Porto Alegre 2, which also occurs in other places in
      Brazil, as well as in India, Pakistan, and Turkey. The results were integrated
      with those obtained in other studies in South America, yielding a total of 16,941
      Amerindians and 23,839 non-Indian subjects. Molecular and physiological studies
      performed in some of the variants suggested clues to explain the restricted
      distribution of albumin Yanomama 2 and the widespread occurrence of albumin Maku.
      Am. J. Hum. Biol. 11:359-366, 1999. Copyright 1999 Wiley-Liss, Inc.

PMID- 11533957
TI  - Fluctuating asymmetry and canalization: An appraisal based on a-b ridge counts
      among Indian populations with diverse backgrounds.
AB  - The relationship between fluctuating asymmetry, measured as the absolute
      difference between the right and left a-b ridge counts, and total a-b (R + L)
      ridge count was studied in an assortment of Indian population samples
      representing a wide spectrum of socioeconomic and occupational backgrounds. They
      included marine fishermen, inland and estuarine fishermen as well as migrants and
      their parental counterparts, tribes, and castes of different hierarchy- lower,
      middle, and upper. The samples together numbered a total of 3,239 subjects, 2,240
      males and 999 females. The results failed to support Jantz and Webb's (1980)
      hypothesis of a quadratic relationship between fluctuating asymmetry of a-b ridge
      count and its phenotypic value. Only 3 of 22 samples (about 13%) showed a
      significant fit with a reasonable degree of consistency over a set of independent
      random subsamples; even initially only 7 of 22 (about 30%) samples showed a
      significant fit, or nearly so. Supplementary evidence drawn from these
      populations with reference to the relationship between fluctuating asymmetry and
      heterozygosity levels and inbreeding coefficients was also consistent with the
      interference that fluctuating asymmetry of a-b as it is measured and examined at
      the population level does not reflect canalization. Am. J. Hum. Biol. 11:367-381,
      1999. Copyright 1999 Wiley-Liss, Inc.

PMID- 11533958
TI  - Effect of developmental and ancestral high altitude exposure on chest morphology
      and pulmonary function in Andean and European/North American natives.
AB  - Chest depth, chest width, forced vital capacity (FVC), and forced expiratory
      volume (FEV1) were measured in 170 adult males differing by ancestral (genetic)
      and developmental exposure to high altitude (HA). A complete migrant study design
      was used to study HA natives (Aymara/Quechua ancestry, n = 88) and low altitude
      (LA) natives (European/North American ancestry, n = 82) at both altitude (La Paz,
      Bolivia, 3,600 m) and near sea level (Santa Cruz, Bolivia, 420 m). HAN and LAN
      migrant groups were classified as: N(th) generation migrants, born and raised in
      a non-native environment; child migrants who migrated during the period of growth
      and maturation (0-18 yrs); and adult migrants who migrated after 18 years of age.
      Chest depth, FVC, and FEV1 measures were larger with increasing developmental
      exposure in both HAN migrants at LA and LAN migrants at HA. Developmental
      responses were similar between HAN and LAN groups. FVC and FEV1 measures were
      larger in HANs vs LANs born and raised at HA to suggest a genetic effect, but
      were similar in HANs and LANs born and raised at LA. The similarity of HAN and
      LAN groups at LA suggests that the genetic potential for larger lung volumes at
      HA depends upon developmental exposure to HA. Additional data for females (HANs
      at HA, n = 20, and LAN adult migrants to HA, n = 17) show similar differences as
      those shown between male HAN and LAN groups. Am. J. Hum. Biol. 11:383-395, 1999.
      Copyright 1999 Wiley-Liss, Inc.

PMID- 11533960
TI  - Bone lead in the prehistoric population of Gran Canaria.
AB  - The present study determined the lead concentration in bone tissue from 40
      prehistoric individuals of Gran Canaria, and in a sample of 19 modern day
      residents of the Canary Islands. Higher bone lead values were observed in the
      modern sample (18.65 +/- 12.13 &mgr;g/g dry bone tissue) than in the ancient
      sample (4.41 +/- 3.45 &mgr;g/g dry bone tissue, P < 0.001). Older individuals
      showed higher bone lead values than younger individuals, but only in the modern
      group. The correlation between age and bone lead approached statistical
      significance (P = 0.058). Low bone lead observed in the prehistoric sample
      suggests a low lead exposure in prehispanic times in Gran Canaria. Am. J. Hum.
      Biol. 11:405-410, 1999. Copyright 1999 Wiley-Liss, Inc.

PMID- 11533962
TI  - Letter to the Editor.

PMID- 11533961
TI  - In memoriam: Barbara Honeyman Heath Roll (1910-1998).

PMID- 11533963
TI  - Response.

PMID- 11533964
TI  - An approach to estimating bone and joint loads and muscle strength in living
      subjects and skeletal remains.
AB  - Skeletal physiology that clarified after 1990 shows that bone modeling normally
      makes a bone strong enough to keep its loads from causing strains above a
      "modeling threshold". That arrangement adapts bone strength to the largest loads
      on a bone, which are usually brief and infrequent. Accordingly, in bone adapted
      chiefly to uniaxial compression loads, the modeling threshold's value and the
      cross-sectional amount of that bone could suggest the size of those loads. Bone
      loaded in that way does support the articular surfaces of synovial joints as
      their "supporting bone", so its amount could suggest the size of the loads it had
      adapted to, and therefore the loads on the joint that it supports. During growth
      a joint's size is proportional, directly but not linearly, to the size of its
      total loads, so that its size at skeletal maturity could be an index of those
      loads at that time. Joints cannot decrease in size. Yet throughout life their
      supporting bone can decrease or increase in strength and "mass" to adapt to
      changes in a joint's loads. Thus, an adult joint's size could suggest the size of
      the loads it adapted to by skeletal maturity, while the cross-sectional amount of
      its supporting bone at any later age could reveal the size of those loads at that
      later age, and thus suggest any change in those loads that might have occurred
      after skeletal maturity. Since the bone modeling threshold, and the relationships
      between bone strain, stress, and unit loads are now known, it is possible with
      this procedure to estimate the total loads on joints, and how body weight and
      muscle strength contribute to those loads in both living subjects and skeletal
      remains. To make a reliable technology of the idea involves some problems which
      this paper identifies and suggests how to resolve. Am. J. Hum. Biol. 11:437-455,
      1999. Copyright 1999 Wiley-Liss, Inc.

PMID- 11533965
TI  - Effect of DHA-containing formula on growth of preterm infants to 59 weeks
      postmenstrual age.
AB  - Between May 1993, and September 1994, a randomized, blinded clinical trial was
      conducted to evaluate measures of growth and body composition in 63 (32 males; 31
      females) healthy, low-birth-weight infants (940-2250 g) who were randomly
      assigned to an infant formula with docosahexaenoic acid (22:6n3, DHA, 0.2 wt%)
      from fish oil or to a control formula. A preterm formula with or without DHA was
      fed beginning at 7-10 days prior to hospital discharge through 43 weeks
      postmenstrual age (PMA). Then, from 43-59 weeks PMA, infants were fed a term
      infant formula with or without a corresponding amount of DHA. Growth (weight,
      length, head circumference), regional body fatness (triceps, subscapular,
      suprailiac skinfold thicknesses), circumferences (arm, abdominal, chest), and
      estimates of body composition determined by total body electrical conductivity
      (TOBEC) (fat-free mass [FFM]) were evaluated. Growth was slower in males fed the
      DHA formula. They had significantly (P < 0.05) smaller gains in weight, length,
      and head circumference between study enrollment to 59 weeks PMA than those fed
      the control formula. At 51 weeks PMA, males in the DHA group had significantly
      smaller head circumferences (P < 0.05) and lower FFM (P < 0.05). At 59 weeks PMA,
      males in the DHA group weighed less (P < 0.05), had shorter recumbent lengths (P
      < 0.01), smaller head circumferences (P < 0.05), and lower FFM (P < 0.01) than
      those fed the control formula. Energy intakes from formula (kcal/d), however,
      were lower at 51 weeks (P < 0.05) and 59 weeks (P < 0.05) PMA in males fed the
      DHA formula. Adjusted for body weight (kcal/kg/d), mean energy intakes from
      formula at 51 and 59 weeks PMA were not significantly different between feeding
      groups. The differences in recumbent length, head circumference, and FFM remained
      statistically significant after controlling for energy and protein intakes (P <
      0.01). For all males, neither FFM nor total body fat (TBF), when expressed as a
      percentage of total body weight, differed significantly between feeding groups.
      Among females, there were no significant differences between the feeding groups
      in measures of growth, body composition, or energy intake. The results indicated
      that infant formula with fish oil containing DHA and EPA in a 5:1 ratio had a
      significant, negative effect on growth and body composition in males during the
      first 6 months of life. It is not clear why the growth deficits were limited to
      males and not females. The eicosanoids, bioactive metabolites of omega-3 and
      omega-6 fatty acids, may mediate several important growth hormones. The present
      results do not support the addition of DHA alone in infant formulas. Am. J. Hum.
      Biol. 11:457-467, 1999. Copyright 1999 Wiley-Liss, Inc.

PMID- 11533966
TI  - Blood pressures of Sherpa men in modernizing Nepal.
AB  - The relationship among potential risk factors (diet, adiposity, physical activity
      levels (PALs), and age) for elevated blood pressures (BP) was examined in 253
      Sherpa men living in Kathmandu (low altitude sample: LAS) and in the Khumbu (high
      altitude sample: HAS) regions of Nepal. The study is based on data collected to
      assess nutritional status. Elevated BPs were highly prevalent among both samples
      of men (LAS: 21.7% and HAS: 24.8%). The highest percentage of elevated BP was
      found among the urban HAS (32.4%), while rural HAS had the lowest percentage
      (16.1%). Stepwise regression analyses showed that the BMI, age, and alcohol
      consumption were strong predictors of systolic blood pressure (SBP), and the BMI
      and age were strong predictors of diastolic blood pressure (DBP). No correlations
      were found among BP and intakes of sodium, calcium, potassium, or fat when all
      men (normotensive and elevated BP) were examined. Bivariate association between
      the BMI and BP showed that obese men were 8.6-9.1 times more likely to have
      elevated BP, and that alcohol consumers were 2.6 times more likely to have
      elevated BP. The results suggest that elevated BP is a problem for a large
      portion of male Sherpas and appears to be associated with an elevated BMI. A
      survey of the region only 30 years ago showed no cases of hypertension.
      Increasing adiposity, due primarily to decreasing PALS, places this population at
      risk of chronic illness in the future. Am. J. Hum. Biol. 11:469-479, 1999.
      Copyright 1999 Wiley-Liss, Inc.

PMID- 11533967
TI  - Heterogeneity of Y chromosome markers among Brazilian Amerindians.
AB  - The allele frequency distribution of DYS19 and DYS199 loci were analyzed in 59
      Brazilian Amerindians from five tribes from the Amazon region (Zoe, Awa-Guaja,
      Urubu-Kaapor, Katuena, and Kayapo, Xikrin of Bacaja village). Three different
      alleles of the DYS19 microsatellite (182-bp, 186-bp, and 190-bp) were found at
      average frequencies of 0.08, 0.85, and 0.07, respectively. The DYS199-T allele
      was identified in 78% of the Amerindians studied (43/55), the frequencies varying
      from 0.46-0.93. Four different haplotypes were found, the combination DYS19
      186/DYS199-T being the most common (average frequency of 0.65), followed by DYS19
      186/DYS199-C with an average frequency of 0.22. These four haplotypes have been
      found in five other Brazilian tribes, and most of them were also identified in
      Native populations from South, Central and North America. The observed
      variability at the DYS19 microsatellite is probably due to forward or back
      mutations from the putative ancestral 186-bp allele, since the mutation rate of
      this locus is high and the post-Columbian admixture of the Brazilian tribes
      studied is very low or undetectable to explain these data. On the other hand, the
      DYS19/DYS199 haplotype distribution may suggest that the two most common
      haplotypes (186-bp/T and 186-bp/C) were present among the population(s) that
      peopled the New World. Am. J. Hum. Biol. 11:481-487, 1999. Copyright 1999 Wiley
      Liss, Inc.

PMID- 11533969
TI  - Maturation-related deviations and misclassification of stature and weight in
      adolescence.
AB  - The present research quantifies normal deviations in stature and weight
      associated with variation in maturational status and describes the associated
      misclassification that occurs when using reference data based on chronological
      age. Misclassification is the likelihood that incorrect judgments will be made in
      assessments relative to the reference data. Based on data for 999 children of the
      Brush Foundation study, the absolute deviations associated with variation in
      maturational status, an index of misclassification &Pcirc;(mc.5) was developed to
      estimate the approximate probability of misclassification within an age group
      relative to that occurring at 5 years of age. The estimated maturation-associated
      deviations and &Pcirc;(mc.5) include changes in age-specific standard deviations
      in skeletal age (mean of hand, foot, elbow, knee, hip, shoulder) and regression
      coefficients (slopes) of stature-for-skeletal age and weight-for-skeletal age.
      Maturation-associated deviations for stature reach 11 cm for boys and 9 cm for
      girls, and those for weight reach 12 kg and 10.5 kg for boys and girls,
      respectively. &Pcirc;(mc.5) for stature at peak velocity reaches 1.3 and 2.3 in
      girls and boys, respectively. These levels indicate that at these ages girls will
      be approximately 1.3 times, and boys 2.3 times, as likely to have their statures
      misclassified because of maturational status than at 5 years of age. For weight,
      &Pcirc;(mc.5) reaches 2.0 by approximately 9 years of age in both sexes and
      reaches 3.1 for girls and 4.9 in boys during adolescence. The adolescent increase
      in maturation-related misclassification results primarily from changes in the
      size-for-maturation relationships rather than changes in the variation in
      maturational status per se. Am. J. Hum. Biol. 11:499-504, 1999. Copyright 1999
      Wiley-Liss, Inc.

PMID- 11533968
TI  - Role of genetic and environmental factors in the increased blood pressures of
      Bolivian blacks.
AB  - The tendency toward hypertension or higher blood pressure is more common in
      blacks than whites. The factors that account for these differences are attributed
      to both environmental and genetic factors. To clarify this issue, an
      anthropological study of black and nonblack populations in the lowland village of
      Chicaloma, northeastern Bolivia at a midaltitude of 1,800 m was conducted. The
      study included 159 subjects, of which 79 were black and 80 were nonblack, 17-78
      years. The study suggests the following: (1) the socioeconomic status of blacks
      as measured by an ownership index is greater than that of nonblacks, (2) blacks
      had higher average systolic and diastolic blood pressures than nonblacks and
      showed an age-associated increase in blood pressures, (3) the prevalence of
      hypertension was higher for blacks (7-6%) than nonblacks (1.3%), but three times
      lower than among blacks in the United States, (4) skin reflectance is inversely
      related to blood pressures so that contrary to what has been suggested the darker
      the skin color, the higher the blood pressures even at comparable levels of
      affluence. These findings together suggest that genetic factors predispose black
      individuals to increased blood pressures, but the expression of clinical
      hypertension is influenced by adverse unaccounted environmental factors. Am. J.
      Hum. Biol. 11:489-498, 1999. Copyright 1999 Wiley-Liss, Inc.

PMID- 11533970
TI  - Relation between birth weight at term and growth rate, skeletal age, and cortical
      bone at 6-11 years.
AB  - There is an apparent link between fetal and childhood growth and puberty and risk
      for several degenerative diseases in adulthood. It is also important to consider
      associations between birth weight and indicators of growth and biological
      maturation during childhood and adolescence as potential explanations for
      associations between fetal growth and adult risk for disease. The present study
      examines the association between birth weight and (1) size attained and rate of
      growth in body size and cortical bone area of the second metacarpal (M II), and
      (2) skeletal age and rate of skeletal maturation in children 6-11 years of age.
      The sample included 127 boys and 105 girls of European ancestry, divided into two
      age groups, 6-8 years and 9-11 years. The relationship between birth weight and
      attained size (stature, mass, and the BMI), M II cortical area and skeletal age
      (SA, Tanner-Whitehouse method) during childhood was examined with correlational
      analyses. Observations on children measured on two occasions were converted to
      annual velocities, and correlations between birth weight and annual velocities
      were also calculated. Birth weight is significantly associated with stature and
      mass in boys and only with stature in girls 6-11 years of age, but is not related
      to the BMI, M II cortical area, or skeletal maturity. Birth weight is not
      significantly related to annual velocities of growth in stature, mass, the BMI
      and M II cortical area; to the annual increment in SA; and to weight gain from
      birth to the time of measurement (intervals of 6 to 11 years). The results
      emphasize a role of other influences than birth weight on growth rate, cortical
      area of M II, and skeletal maturation during childhood. Am. J. Hum. Biol. 11:505
      511, 1999. Copyright 1999 Wiley-Liss, Inc.

PMID- 11533971
TI  - Enamel hypoplasia in a Canadian historic sample.
AB  - Analyses of historical skeletal samples provide useful comparisons of the
      prevalence of skeletal indicators of stress to documentary information on health,
      diet, and socioeconomic status. A sample of the permanent dentitions of 253
      adults from the St. Thomas' Anglican Church 19th-century skeletal sample in
      Belleville, Ontario, was examined macroscopically for the prevalence of enamel
      defects on the six anterior maxillary and mandibular teeth. The maximum frequency
      of hypoplasias on the left mandibular canine is 36.1%. The prevalence of enamel
      defects is low to moderate compared to almost all other reported frequencies in
      historical samples, which is consistent with historical descriptions of this
      developing community of middle to high socioeconomic status Canadians.
      Hypoplasias are significantly more frequent in males but there are no significant
      differences in the mean age at death between individuals with hypoplasia and
      those without. Calculations of the peak ages of occurrence of hypoplasias fall
      within the commonly observed 2-4-year range. This is not consistent with separate
      studies, demographic, isotopic and historical, of the introduction of
      complementary foods to 19th-century Belleville infants and of the weaning
      process. These results do not support the view that peak ages of occurrence of
      hypoplastic defects are associated with the cessation of breast-feeding or the
      weaning process in general. Am. J. Hum. Biol. 11:513-524, 1999. Copyright 1999
      Wiley-Liss, Inc.

PMID- 11533972
TI  - Blood groups and red cell acid phosphatase types in a Mixteca population resident
      in Mexico City.
AB  - Several blood groups, ABO, Rh, Ss, Fy, Jk, and red cell acid phosphatase (ACP)
      types were studied in a native Mixteca population that has resided in Mexico City
      since 1950. Gene frequencies were obtained and used to establish admixture
      estimates with blacks and whites. The subjects came from three different
      geographical areas: High Mixteca, Low Mixteca, and Coast Mixteca. All frequencies
      were in Hardy-Weinberg equilibrium. The difference in the ABO frequencies was
      statistically significant when subjects from the three areas were compared
      simultaneously. Rh frequencies differed only between the High and the Low Mixteca
      populations. The ACP frequencies were similar between the Low Mixteca population
      and a previously reported Mestizo population. However, there were significant
      differences between the High Mixteca group and a Mestizo population, all the
      subjects being from Oaxaca. This is the first report of Ss, Fy, Jk, and ACP
      frequencies in a Mixteca population. Am. J. Hum. Biol. 11:525-529, 1999.
      Copyright 1999 Wiley-Liss, Inc.

PMID- 11533973
TI  - Modeling dynamic skinfold compression.
AB  - Real time compression of skinfolds was measured at three sites (triceps,
      abdominal medial calf), using a Slim Guide skinfold caliper adapted by the
      addition of a potentiometer, on eight males and eight females (age range 18-40
      years). An average of eight trials for each subject at each site was used in
      modeling the compression curves. A mechanical model was developed, comprised of
      two parallel spring and viscous components in series with each other. $ Tt =
      Tinitial + F ?left( { 1 ?over k_1 } - ?left?lceil { e { -k_1 t ?over b_1 } ?over
      k_1 } ?right?rceil ?right) + F ?left( { 1 ?over k_2 } - ?left?lceil { e { -k_2 t
      ?over b_2 } ?over k_2 } ?right?rceil ?right) $ where: Tt = thickness at time t;
      Tinitial = intial skinfold thickness; F = force exerted by caliper; k(1) and k(2)
      = coefficients of elasticity; b(1) and b(2) = coefficients of viscosity. This two
      component model was the best fitting model in comparison to one or three
      component alternatives. The coefficients of the model were different by sex and
      skinfold site. Coefficients for females showed greater elasticity and less
      viscosity compared to those for males. Further, there appeared to be a systematic
      site difference with the triceps having less elasticity and viscosity in both
      sexes. Am. J. Hum. Biol. 11:531-537, 1999. Copyright 1999 Wiley-Liss, Inc.

PMID- 11533975
TI  - African-derived South American populations: A history of symmetrical and
      asymmetrical matings according to sex revealed by bi- and uni-parental genetic
      markers.
AB  - Estimates of African, European, and Amerindian contributions to the gene pool of
      11 predominantly African-derived South American populations were obtained using
      five autosomal and one Y chromosome hypervariable loci, as well as mitochondrial
      DNA (sequences of the first hypervariable segment of the control region, plus two
      restriction sites and the presence or absence of the CoII/tRNA(Lys) intergenic 9
      bp deletion). The three latter characteristics are reported here for the first
      time for 42 individuals living in three Brazilian populations. Thirty-eight
      sequences were identified in these persons; 17 (45%) could be classified as being
      of African, 4 (11%) of Amerindian, and 2 (5%) of European origin. Evidence for
      asymmetrical matings in relation to sex and ethnic group was obtained for nine of
      the 11 populations. The most consistent finding was the introduction of European
      genes through males, but the results differ in the several communities,
      indicating the importance of local factors in such interactions. Am. J. Hum.
      Biol. 11:551-563, 1999. Copyright 1999 Wiley-Liss, Inc.

PMID- 11533976
TI  - Increased tooth crown size in females with twin brothers: Evidence for hormonal
      diffusion between human twins in utero.
AB  - In rodents, the position of a fetus in utero is associated with the expression of
      sexually dimorphic traits. This phenomenon has been explained by prenatal
      diffusion of sex hormones among litter mates. To test for such effects in humans,
      female-male twin pairs provide a natural experiment. The size of dental crowns is
      a sexually dimorphic trait which can be measured with a high degree of
      reliability. Thus, two crown diameters of 28 permanent teeth were recorded for 56
      opposite-sexed (OS) and 242 same-sexed (SS) twin pairs, and 150 singletons.
      Comparisons of OS twins with SS twins and singletons within each sex reveal that
      OS females have consistently larger teeth (on average) than other females, while
      there is no consistent difference between OS and SS twin males. It is proposed
      that diffusion of sex hormones from male to female co-twins in utero may account
      for the increased tooth size in OS females. This study is one of the first to
      report such an effect on a morphological variable in humans. The finding that the
      maxillary canine, one of the most sexually dimorphic teeth, exhibits the least
      effect in OS female twins, suggests that prenatal sex hormone levels may have
      less impact on sexual dimorphism in the maxillary canines than in other permanent
      teeth. Am. J. Hum. Biol. 11:577-586, 1999. Copyright 1999 Wiley-Liss, Inc.

PMID- 11533977
TI  - Associations between daily physical activity and physical fitness in Flemish
      males: A cross-sectional analysis.
AB  - The relationship of physical activity to several components of physical fitness
      was investigated in a sample of 166 males 40 years of age. In addition to Pearson
      correlations, multivariate canonical correlations were calculated. Physical
      activity during work (work index), sport (sport index), and leisure time (leisure
      time index) was assessed by the Baecke questionnaire. Physical fitness included
      cardiorespiratory fitness measures, the body mass index (BMI), the sum of seven
      skinfold thicknesses (SKI), percentage body fat (PFAT), balance, and several
      tests of muscle strength and endurance, flexibility, and speed of limb movement.
      More than 86% of the variance was shared by the two first canonical variables.
      The first canonical variable can be interpreted as a health-related fitness
      function. Carciorespiratory fitness, balance, speed of limb movement, explosive
      strength, and trunk muscle strength are clearly related to this function. From
      the physical activity measures, the Baecke sport index correlated significantly
      with this health-related fitness function. The second canonical variable can be
      explained as a fatness function, since body weight, BMI, SKI, and PFAT showed the
      highest correlations with the variable. The Baecke work index was inversely
      related to this canonical variable. The sample was also divided into physical
      activity groups in order to look for differences in physical fitness. The data
      indicate that physical activity during work was modestly, but inversely related
      to adiposity. Sport activity was beneficially associated to several fitness
      components, including cardiorespiratory fitness, trunk muscle strength, and upper
      body muscular endurance. Am. J. Hum. Biol. 11:587-597, 1999. Copyright 1999 Wiley
      Liss, Inc.

PMID- 11533978
TI  - Peripartum cocaine use and adverse pregnancy outcome.
AB  - The objective of the study was to analyze possible adverse effects of peripartum
      cocaine use on maternal and fetal outcomes. Informed consent was given by 720
      (97%) of 740 women who delivered consecutively at a large urban public hospital
      to test an umbilical cord blood sample for the presence of non-medically
      administered drugs of abuse and alcohol and to be interviewed for the study.
      Samples were tested for the presence of a cocaine metabolite (benzoylecgonine
      BZE) by radioimmunoassay. The presence of other substances of abuse (alcohol,
      methamphetamine, opiates) resulted in exclusion from the sample of 143 subjects.
      Thus, in this cohort analysis, drug-free controls (N = 469) were compared to
      those positive for cocaine only (N = 108). Peripartum exposure to cocaine only,
      and no other substances of abuse, was associated with an increased frequency of
      abruptio placentae (1.9% vs 0% for control, P < 0.004), thick meconium stained
      amniotic fluid (3.9% vs 0.7% for controls, P < 0.006), premature rupture of
      membranes (P < 0.02), genitourinary anomalies (OR = 3.6, P < 0.05), abdominal
      wall defects (OR = 4.4, P < 0.01) and increased frequency of low birth weight (OR
      = 2.0, P < 0.02). These are important findings because previous studies have been
      complicated by the confounding effects of other substances of abuse. Am. J. Hum.
      Biol. 11:598-602, 1999. Copyright 1999 Wiley-Liss, Inc.

PMID- 11533979
TI  - Interethnic genetic differentiation: HLA class I antigens in the population of
      Mongolia.
AB  - A total of 1668 individuals representing 10 major Mongolian ethnic groups were
      serologically typed for HLA-A, -B, and -C antigens. Antigens A2, A24, B61, B51,
      B58, Cw3, Cw7, and Cw6 were the most frequent specificities in Mongolians and no
      case of B42 was noted in all ethnic groups. The cluster analysis of Principal
      Components I and II shows that Mongolian speaking groups form one cluster vs
      Turkic-speaking Kazakhs. The analysis reveals a low, but significant
      differentiation of Mongolian ethnic groups as measured by F(ST) = 0.0100 (P <
      0.001). Gene diversity analysis shows that the genetic diversity of the Mongolian
      population can be attributed largely to its ethnic component, which makes up 64%
      of total genetic variation. The low degree of interpopulation variation and high
      level of intrapopulation diversity can be explained by the nomadic way of life of
      this indigenous population. Three-locus haplotypes A24-B61-Cw3, A33-B58-Cw3 are
      the most common haplotypic associations in Mongolians. The presence of antigens
      characteristic of Mongoloid, Caucasoid, and Negroid populations in Mongolians
      suggests a unique genetic background of this indigenous population. The three
      locus haplotype distribution among Mongolians relative to other world populations
      supports the migration of ancient people from Central Asia to the New World,
      Korean Peninsula, and Southeast Asia. Am. J. Hum. Biol. 11:603-618, 1999.
      Copyright 1999 Wiley-Liss, Inc.

PMID- 11533980
TI  - Sexual dimorphism in the relationship between number of emerged permanent teeth
      and percentage of adult stature.
AB  - The relationship between the number of emerged teeth and statural growth was
      investigated in a sample of 31 boys and 42 girls followed longitudinally from 6
      12 years of age. The number of emerged permanent teeth was counted on the total
      number of plaster dental casts. Percentage of adult stature attained at a given
      age was calculated on the basis of predicted adult stature at 25 years of age
      using the BTT model. Percentage of permanent teeth emerged was based upon 28
      teeth, the number of all permanent teeth except for the third molars. Girls
      attained a greater percentage of adult stature at each age, but there was no
      clear sex difference in the percentage of emerged teeth. However, when expressed
      on the basis of %adult stature, there was clear sex difference in %emerged teeth.
      The results suggest a sex difference in %emerged teeth that is specific to the
      %adult stature that has been attained. Am. J. Hum. Biol. 11:619-626, 1999.
      Copyright 1999 Wiley-Liss, Inc.

PMID- 11533981
TI  - The timing of maternal weight gain during pregnancy and fetal growth.
AB  - The morbidity, mortality, and growth patterns of intrauterine growth retarded
      (IUGR) infants vary according to body proportionality, or the ponderal index.
      Much less in known, however, about the factors that give rise to the various
      forms of IUGR. This study tests that hypothesis that the rate of maternal weight
      gain during early/mid and late pregnancy are differentially related to body size
      and proportions at birth in a nutritionally stressed population in rural Malawi.
      The data consist of prospectively collected measurements of maternal weight and
      infant size at birth on 272 mother-infant pairs. The results reveal that
      early/mid and late weight gain are both related to birth weight and length, but
      not to the ponderal index. Late weight gain is particularly predictive of infant
      size among thin women (BMI </= 18.5) and is several times stronger than early/mid
      weight gain. These findings do not support the timing hypothesis as previously
      stated in the literature, but do add to the suggestions arising from a disparate
      literature that growth acceleration in length may precede acceleration in weight
      for-length during a period of nutritional replection in phases of the life cycle
      characterized by rapid growth. Am. J. Hum. Biol. 11:627-637, 1999. Copyright 1999
      Wiley-Liss, Inc.

PMID- 11533982
TI  - The timing hypothesis and body proportionality of the intra-uterine growth
      retarded infant.
AB  - Intra-uterine growth retardation (IUGR) is a heterogeneous designation, as seen
      in the fact that neonatal morbidity and mortality differ for IUGR infants that
      are disproportionate vs proportionate based on the ponderal index
      (weight/height(3)). Much less is known, however, concerning the etiology of these
      two forms. This study tests the hypothesis that the form of IUGR (proportionate
      vs disproportionate) is related to the timing of stress during gestation,
      specifically, that linear growth is compromised by second trimester stress and
      the ponderal index is compromised by third trimester stress. This hypothesis is
      tested using data on 755 full-term mother-infant pairs studied prospectively in
      rural northern Malawi where the seasonal stress of the pre-harvest rainy season
      (PHRS) is a regular occurrence. The results indicate that exposure to PHRS in the
      second trimester is not associated with weight, length, or the ponderal index at
      birth. Exposure to PHRS in the third trimester is associated with diminished
      birth weight and length, but not ponderal index. The results do not support the
      timing hypothesis, at least as previously framed in the literature, and suggest
      the possibility that linear growth may precede or be more sensitive to prenatal
      stress than the ponderal index. Am. J. Hum. Biol. 11:638-646, 1999. Copyright
      1999 Wiley-Liss, Inc.

PMID- 11533983
TI  - Heart rate indicators for assessing physical activity level in the field.
AB  - The reliability and validity of heart rate (HR) indicators for assessing physical
      activity level (PAL) was examined in 16 male and female farmers in northeast
      Thailand. For each subject, daytime HRs were monitored for 12 days, 4 days each
      in three agricultural seasons in a year. At the group level, the percentage of
      time when HR exceeded flex-HR (%Flex) had the highest reliability as an indicator
      of PAL even in the season of lowest activity (r > 0.91 in males and r > 0.89 in
      females). Regarding the reliability of each subject's %Flex for assessing PAL,
      regression analyses revealed coefficients of determination of 0.73-0.97 in males
      and 0.62-0.97 in all females except one. Analyses of covariance (ANCOVA), with
      %Flex as a covariate, showed that the difference among the slopes of PAL of
      different subjects was not significant in females, but was in males (P = 0.003).
      Comparison of measured PAL values and corresponding PAL values estimated by a
      regression equation for all subjects showed that 75% were within +/-0.2; further,
      PAL values tended to be underestimated in cases when they exceeded 2.0 for males.
      The results for these Thai-Lao subjects are consistent with previous studies on
      other populations; thus, it may be concluded that %Flex is reliable and valid for
      assessing PAL for a group of subjects and for assessing intraindividual
      variability of PAL. Am. J. Hum. Biol. 11:647-657, 1999. Copyright 1999 Wiley
      Liss, Inc.

PMID- 11533984
TI  - Age, reproductive history, seasonality, and maternal body composition during
      pregnancy for nomadic Turkana of Kenya.
AB  - To evaluate the potential differences in maternal nutritional investment in
      pregnancy, data collected from nomadic Ngisonyoka Turkana women during a July
      1993-July 1994 field season were utilized. The roles maternal age, parity,
      duration of the previous nonpregnant interval, overlap between pregnancy and
      lactation on trimester changes in weight and summed skinfolds during pregnancy
      were examined. Because seasonality is an important aspect of the Turkana
      environment, the effects of seasonality were also assessed. First trimester
      weight gain is positively associated with overlap in pregnancy and lactation.
      Second trimester maternal weight gain is negatively influenced by higher parity
      and by overlap between lactation and early pregnancy. Third trimester weight gain
      is influenced only by seasonally induced morbidity. First trimester changes in
      maternal skinfolds are negatively influenced by older maternal age and parity,
      and positively influenced by a longer nonpregnant interval, and overlap between
      pregnancy and lactation. Second and third trimester skinfolds are significantly
      associated only with overlap between lactation and pregnancy (negatively in the
      second, positively in the third). Seasonality does not influence maternal
      skinfolds. Differences in age- and parity-related patterns of maternal
      nutritional investment in pregnancy are not supported by the data. The
      possibility that Turkana cultural beliefs may influence nutritional status during
      pregnancy is discussed. Am. J. Hum. Biol. 11:658-672, 1999. Copyright 1999 Wiley
      Liss, Inc.

PMID- 11533985
TI  - Weight, stature, and body mass index data for Mexican Americans from the third
      national health and nutrition examination survey (NHANES III, 1988-1994).
AB  - Selected age- and sex-specific percentiles are presented for 4,054 Mexican
      American children ages 1-18 years who were included in the third National Health
      and Nutrition Examination Survey (NHANES III, 1988-1994). These percentile values
      are compared with corresponding percentiles for Mexican Americans from the
      Hispanic Health and Nutrition Examination Survey (HHANES, 1982-1984). In each
      sex, the weight and weight/stature(2) percentiles from NHANES III were
      significantly larger than those from HHANES. For weight, the NHANES III values
      tended to be clearly larger after 11 years in males and females, and they were
      larger for weight/stature(2) at the 50th and 90th percentiles in each sex after 6
      years. For stature, the NHANES III values were significantly larger at the 90th
      percentile among females, but the differences were not significant for any other
      percentiles among females or males. In comparison with non-Hispanic White
      children, Mexican American children tend to be shorter and heavier, especially
      after the preschool period. The similarity of the findings for stature from
      NHANES III and HHANES indicates that the shorter statures of Mexican Americans
      are not cohort-specific. The tendency to larger values for weight/stature(2) in
      Mexican Americans has important public heath implications since this ratio tends
      to track after early childhood, and high ratios in adulthood constitute an
      important risk factor for common diseases such as diabetes mellitus and coronary
      heart disease. Am. J. Hum. Biol. 11:673-686, 1999. Copyright 1999 Wiley-Liss,
      Inc.

PMID- 11533986
TI  - Effect of exclusion: Rates of hysterectomy and comparisons of age at natural
      menopause.
AB  - The objectives of this study were to identify factors related to history of
      hysterectomy; to evaluate whether or not subgroups with different rates of
      hysterectomy also report significantly different mean ages at natural menopause;
      and to consider how variation in rates of hysterectomy may affect intrapopulation
      and cross-population comparisons of median ages at natural menopause. Data were
      drawn from a community sample in upstate New York. It is demonstrated that
      hysterectomy rates are not random with respect to variables that are also related
      to age at natural menopause. For example, women reporting high levels of
      education reported lower rates of hysterectomy and earlier mean ages at
      menopause. In addition, median ages at menopause and rates of hysterectomy were
      examined by correlation and regression analysis across a selection of
      industrialized countries. Avenues for further study are suggested. Am. J. Hum.
      Biol. 11:687-693, 1999. Copyright 1999 Wiley-Liss, Inc.

PMID- 11533987
TI  - Evolutionary process and the ecology of human immune function.
AB  - Evolutionary principles inform central design features of human immune defenses
      and provide key insights into this complicated host defense system. This article
      explores the selection pressures and adaptive responses that have elaborated the
      immune system over the course of evolution and discusses their implications for
      understanding contemporary immune development and function. Special attention is
      given to the challenges posed by diverse, rapidly evolving pathogens and the
      mammalian response to these challenges. The process of lymphocyte diversity
      generation and subsequent clonal selection is quintessentially Darwinian:
      pathogens provide selection pressure that drives differential replication of host
      immune cell lines, resulting in changes in genetic frequencies within an
      individual's population of lymphocytes. The immune system also incorporates
      nongenetic transgenerational processes in the transfer of antibodies from mother
      to offspring through the placenta and breast milk. The consequences of these
      observations for human development, health, and the ecology of immune function
      are considered throughout the life cycle. Specifically, evolutionary processes
      provide insight into autoimmunity, thymic function, lymphocyte development,
      infectious disease risk, and lactation. While much work in evolutionary medicine
      focuses on the discordance between evolved biology and rapidly changing cultural
      environments, with respect to the immune system, evolutionary processes may be
      most revealing when applied within individuals. Am. J. Hum. Biol. 11:705-717,
      1999. Copyright 1999 Wiley-Liss, Inc.

PMID- 11533988
TI  - Interproximal contact hypoplasia in primary teeth: A new enamel defect with
      anthropological and clinical relevance.
AB  - This study reports the prevalence, distribution, and expression of enamel defects
      in a sample of primary teeth (n = 225) from a prehistoric site in western India
      (1400-700 BC). Five enamel surfaces of individual, isolated primary teeth were
      observed for surface defects using a binocular stereomicroscope with variable
      power of magnification (8-20x). Standards for evaluating dental enamel defects
      (DDE) recommended by the Federation Dentaire International (FDI) were employed.
      Details of defect expression were also recorded, including size, shape, and
      surface of tooth crown affected. Hypoplastic enamel defects were observed in 28%
      of teeth, but the distribution and expression of defects was not random. More
      than 50% of canine teeth had hypoplastic defects (HD); incisors and molar teeth
      exhibited far fewer HD. The buccal surface of canines was the most commonly
      affected crown surface. Areas of missing enamel were also common on the mesial
      and distal surfaces of canines and incisors and on the mesial surface of molar
      teeth. The high frequency of enamel defects found on interproximal crown surfaces
      warrants a label, and the name interproximal contact hypoplasia (IPCH) is
      proposed. Linear enamel hypoplasia (LEH) was absent from this primary dental
      sample. IPCH is more frequent in mandibular than in maxillary teeth, but no side
      preference was detected. In canine teeth, buccal hypoplasias (localized
      hypoplasia of primary canines; LHPC) were not positively correlated with
      interproximal hypoplastic defects. The etiology of IPCH may involve mesial
      compaction of developing teeth due to slow longitudinal growth of the jaws.
      Episodic bone remodeling results in ephemeral fenestrae in the mesial and distal
      walls of the dental crypt permitting tooth-tooth contact and disruption of
      amelogenesis. IPCH prevalence decreases across the subsistence transition from
      sedentary Early Jorwe agriculturalists to seminomadic Late Jorwe hunters and
      foragers, but the difference is not statistically significant. This may be due to
      underrepresentation of mandibular teeth in the sample. Am. J. Hum. Biol. 11:718
      734, 1999. Copyright 1999 Wiley-Liss, Inc.

PMID- 11533989
TI  - Somatic comparisons at four ages of South Korean females and females of other
      Asian groups.
AB  - Somatic data were collected during April 1997 on 156 females ages 6, 9, 13, and
      15 years, residing in urban Pusan, South Korea, and on 158 age peers residing in
      rural regions surrounding the city. Comparisons were made between urban and rural
      groups for measures of body size and form, skinfold thicknesses, the body mass
      index (BMI), and estimated arm muscle area (ARM). Age at menarche was
      retrospectively reported by the 13- and 15-year-olds. The data were analyzed in 2
      (urban-rural) x 3 (age) analyses of variance with an alpha level of P < 0.05. Age
      differences were evident for all dimensions. A significant main effect for urban
      rural differences was found for stature, lower limb height, upper limb height,
      shoulder width, hip width, triceps skinfold, ARM, skelic index, and the trunk
      width index. Regardless of age, urban children were larger than rural children.
      Similar means were obtained for the BMI in urban and rural girls. Age at menarche
      was consistent with recent results; however, the rural sample (12.4 years) was
      significantly earlier than the urban sample (13.1 years). Compared with data
      collected four decades ago, present-day 6-, 9-, 13-, and 15-year-old females are
      taller and heavier at every age, indicating secular gains. Pusan females are
      similar in stature to age peers in Taiwan, Japan, and Hong Kong, and taller than
      the Chinese. Am. J. Hum. Biol. 11:735-744, 1999. Copyright 1999 Wiley-Liss, Inc.

PMID- 11533990
TI  - Genetic relationships between southeastern Spain and Morocco: New data on ABO,
      RH, MNSs, and DUFFY polymorphisms.
AB  - The genetic polymorphism of four blood group systems (ABO, RH, MNSs, and DUFFY)
      was analyzed in two well-defined population samples coming from south-central
      Morocco and southeastern Spain. Both a controversial ancient common substrate and
      the long period of coexistence between North Africa and southern Spain during the
      eight centuries of the Islamic invasion of the Iberian Peninsula suggest a
      particular genetic relationship between northwestern Africa and southern Spain.
      Allele distributions in each sample are in general agreement with that expected
      according to the geographical and historical characteristics in the Mediterranean
      region. However, the differences between the Moroccan sample and other north
      African groups illustrate considerable genetic variability in this geographical
      region. In comparison with other samples from different regions of the Iberian
      Peninsula, the markers examined fail to demonstrate any particular affinity
      between the southern Spanish sample of La Alpujarra and Moroccan populations. Am.
      J. Hum. Biol. 11:745-752, 1999. Copyright 1999 Wiley-Liss, Inc.

PMID- 11533991
TI  - Food and macronutrient intake of economically disadvantaged pregnant women in
      Colombia.
AB  - The objective of this article is to assess changes in diet composition, defined
      in terms of macronutrient intake and types of foods consumed, in pregnancy in
      poor urban women in Colombia. The subjects were 20 pregnant and 20 matched
      nonpregnant, nonlactating (NPNL) women 19 to 35 years of age. The pregnant women
      were studied in three measurement rounds at 14.0 +/- 3.6, 27 +/- 2.2, and 35 +/-
      1.7 weeks gestation, and the NPNL women in three measurement rounds approximately
      3 months apart. Dietary intake was obtained from estimated food records and
      macronutrient composition from published sources. Types of foods consumed were
      aggregated into 16 groups: alcohol; breads; candy; coffee, chocolate; juices;
      fruit; legumes; meat, fish, offal; dairy; vegetable dishes; other; rice, pasta;
      tubers, plantains; salads; soft drinks; and soups. Macronutrient intakes showed
      nonsignificant increases in pregnancy. There were no significant differences
      between pregnant and NPNL women, except for carbohydrate intake in late pregnancy
      (P = 0.03). Carbohydrate, fat, and protein provided 74%, 17%, and 12% of dietary
      energy, respectively, in pregnant women at baseline, and did not change
      significantly. Except for a decrease in fruits, the types of foods consumed did
      not change significantly in pregnancy. There were no between-group differences in
      types of foods consumed except for the greater number of fruits consumed by
      pregnant women at baseline (P = 0.004). We conclude that in this population there
      were no changes in diet composition in pregnancy, except for an increase in fruit
      consumption in Round 1. Am. J. Hum. Biol. 11:753-762, 1999. Copyright 1999 Wiley
      Liss, Inc.

PMID- 11533992
TI  - Gastrointestinal parasitic infection, anthropometrics, nutritional status, and
      physical work capacity in Colombian boys.
AB  - This article tests the hypothesis that the presence of gastrointestinal parasites
      in Colombian boys is negatively associated with anthropometric characteristics,
      physical work capacity, blood hemoglobin (Hb) levels, and nutritional status.
      Anthropometric, Hb, &Vdot;O(2) max, and parasite load data were collected on
      1,016 boys in Cali, Colombia. The boys were classified as lower socioeconomic
      class (SEC) from either urban or rural environments, and upper SEC from an urban
      environment. Sixty-three percent of the boys were infected with gastrointestinal
      parasites and, of the infected boys, 80-95% had light parasite loads. Parasites
      found included Necator americanus, Ascaris lumbricoides, Entamoeba histolytica,
      Trichuris trichiura, Giardia spp., and Enterobius vermicularis. Infected boys had
      significantly lower weight, stature, weight-for-height (among 6-9-year-old boys),
      Hb levels, and &Vdot;O(2) max (ANCOVA, controlling for age and SEC). In terms of
      nutritional status, infected boys were 1.47 times more likely to be classified as
      iron deficient than noninfected boys (chi-square, P < 0.001), and 1.61 times more
      likely to be classified as stunted (P < 0.001). Infection was not associated with
      wasting in any SEC group. In conclusion, light to moderate gastrointestinal
      parasite loads were associated with significantly lower weight, stature, weight
      for-height (in 6-9-year-old boys), Hb levels, and &Vdot;O(2) max, and a
      significantly higher frequency of IDA and stunting. These data suggest that
      comprehensive analyses of the nutritional status of populations in regions
      endemic for parasitic infection should include testing for the presence of
      infection. Am. J. Hum. Biol. 11:763-771, 1999. Copyright 1999 Wiley-Liss, Inc.

PMID- 11533993
TI  - Relationship of birth weight and length with growth in height and body diameters
      from 5 years of age to maturity.
AB  - Birth weight and birth length were compared with several growth measures,
      including body height and weight, linear measures of limbs, body diameters, and
      head circumference, in 726 Melbourne schoolchildren of both sexes age 5-18 years.
      The analysis of relationships between three categories of birth length, weight,
      and growth measures were based on z-scores and performed by using analysis of
      variance and partial correlation. The data showed that birth length was
      correlated with body height and birth weight was correlated with head
      circumference; the relationships were weak and were less clear around the age
      corresponding to the peak height velocity in either sex. Further studies are
      needed to determine the common underlying mechanisms responsible for these
      associations. Am. J. Hum. Biol. 11:772-778, 1999. Copyright 1999 Wiley-Liss, Inc.

PMID- 11533994
TI  - Influence of family size and birth order on menarcheal age of girls from Bilbao
      city (Biscay, Basque country).
AB  - From a sample of 895 girls from Bilbao 9.5 to 18.5 years of age, the possible
      influence of family size and birth order on menarcheal age was analyzed. The
      earliest mean ages of menarche occurred in girls from families of one or four or
      more children, or who occupied the first or last birth order in their families.
      Later mean ages of menarche occurred in girls belonging to sibships with two or
      three children or who occupied the second or third birth order in their families,
      the latest being girls belonging to sibships of three children or of third birth
      order. This may be due to the variations in the interval of time between births,
      leading to better care and less stress for the youngest individual of the family
      and, hence, may be indicative of psychological as well as biological factors
      affecting maturation. Am. J. Hum. Biol. 11:779-783, 1999. Copyright 1999 Wiley
      Liss, Inc.

PMID- 11533995
TI  - Growth studies in Jena, Germany: Changes in thoracic measurements between 1975
      and 1995.
AB  - This article presents the changes in three measurements of the thorax (chest
      depth, breadth, circumference) and in the chest index (chest depth / chest
      breadth) in 7-14-year-old school children from Jena between 1975 and 1995. Apart
      from the description of observed secular trends in body size (thorax measures)
      and form (index) of the thorax, age- and sex-specific differences are described.
      Boys have, on average, higher values of chest depth and chest breadth. Up to the
      age of 10, boys have a larger chest circumference at first, afterwards this is
      true for girls. The thoracic measurements increase under the influence of the
      secular trend. Since the individual measure- ments do not change in the same way,
      the trends suggest changes in proportions. Both sexes show similar secular
      trends, but the secular changes do not occur continuously, only intermittently.
      The results show that such intermittent changes occurred between 1985 and 1995.
      Am. J. Hum. Biol. 11:784-792, 1999. Copyright 1999 Wiley-Liss, Inc.

PMID- 11533996
TI  - Vitamin D receptor polymorphisms and bone mineral density in Mexican women
      without osteoporosis.
AB  - Polymorphisms corresponding to Apa I, Bsm I, and Taq I restriction endonucleases
      at the vitamin D receptor (VDR) gene and bone mineral density (BMD) at lumbar
      spine (L2-L4) and proximal femur (neck, Ward's triangle and trochanteric region)
      sites were examined in a sample of 98 Mexican women (age 55 +/- 10 years). None
      of the subjects were pregnant or nursing and none had a previous diagnosis of
      osteoporosis. Polymorphisms were assessed by the restriction fragment length
      polymorphism - polymerase chain reaction (RFLP-PCR) technique. Alleles were
      denoted with capital letters for the absence of the RFLP site (A, B, or T) and
      with small letters for its presence (a, b, or t). BMD was assessed by dual energy
      X-ray absorptiometry (DXA). A structured, self-administrated questionnaire was
      used to obtain data on age, menopause, number of pregnancies, breast-feeding,
      fractures, exercise, smoking, alcohol, estrogens, calcium supplement, height,
      weight, and BMI. There were no differences between BMD at the skeletal sites and
      the genotypes disclosed by Apa I (Allele A = 0.43), Bsm I (Allele B = 0.26) and
      Taq I (Allele T = 0.76). The present study provides data for comparison with
      other studies to determine the possible value of genotyping VDR to predict
      predisposition for osteoporosis in Mexican or Mexican-American women. Am. J. Hum.
      Biol. 11:793-797, 1999. Copyright 1999 Wiley-Liss, Inc.

PMID- 11533997
TI  - Critical appraisal of the estimation of body composition via two-, three-, and
      four-compartment models.
AB  - Withers RT, Laforgia J, Heymsfield SB. 1999. Critical appraisal of the estimation
      of body composition via two-, three-, and four-compartment models. Am J Hum Biol
      11:175-185. Line 4 of Validity of assumptions should read, 1.565 g/cm(3) instead
      of, 1.555 g/cm(3). The authors regret this error.

PMID- 11533998
TI  - The brush inquiry: An opportunity to investigate health outcomes in a well
      characterized cohort.
AB  - The Brush Inquiry was conducted in Cleveland, Ohio, from 1926-1942 to
      longitudinally document the growth and development of healthy children and
      adults. The Brush population was a heterogenous group with a broad representation
      of racial and socioeconomic groups. Data collection included radiographs of
      several parts of the body; motor, mental, and psychological tests; health,
      nutrition, and prenatal history; body measurements and family history. The early
      results of the inquiry were used to establish standards for normal childhood
      growth and development. Today, many of these subjects (88%) are in the age range
      of 60-80, facilitating the continuity of the inquiry to study early indicators
      for later health outcomes. This article reviews the origins of the inquiry,
      characteristics of the population, and the prospects for future research using
      this cohort. Am. J. Hum. Biol. 12:1-9, 2000. Copyright 2000 Wiley-Liss, Inc.

PMID- 11533999
TI  - The Raymond Pearl memorial lecture, 1997: The quest for medical normalcy-who
      needs it?
AB  - Darwinian natural selection is the only factor in evolution that maintains and
      improves adaptation. It does so by favoring genes that enhance the genetic
      success of their bearers under historically prevalent conditions, and need not
      favor health or happiness or conformity to some universally normal state. It may
      favor unpleasant departures from medical normalcy if they contribute to long-term
      genetic success, either directly or as unavoidable costs of features that make
      such contributions. It is also blind to future consequences of current evolution,
      so that every evolving lineage accumulates historical legacies that may seriously
      constrain future adaptation. Examples of adaptive but unpleasant abnormality are
      found in infectious diseases and other instances of conflict (between the sexes,
      between parent and offspring, between competitors for limited resources).
      Examples of unfortunate historical legacies are found in limitations on numbers
      of parts (limbs, sense organs) and in the tight human birth passage. Adaptation
      is a more useful medical concept than normalcy, but the purpose of medicine is
      not to facilitate natural selection or uncritically encourage biological
      adaptations. Medical intervention may legitimately promote human values by
      frustrating adaptations (e.g., by anesthesia) or by seeking the grossly abnormal
      (e.g., birth through the abdomen rather than the vagina). Am. J. Hum. Biol. 12:10
      16, 2000. Copyright 2000 Wiley-Liss, Inc.

PMID- 11534000
TI  - Color-blindness in Calabria (Southern Italy): A north-south decreasing trend.
AB  - The frequency of color-blindness (CB) in 13,072 males from 409 towns in Calabria
      is 5.42%. Regional variation in CB within the three provinces of Calabria was
      studied: Cosenza (northern), Catanzaro (central), and Reggio Calabria (southern).
      There is a decreasing trend of mean frequencies of CB from Cosenza to Reggio
      Calabria through Catanzaro: 6.23%, 4.65%, and 3.43%, respectively. The mean
      frequencies do not take into account the two ethnic minorities present in
      Calabria: Albanians and Grecanicans. The frequency of CB mean Albanians (7.40%)
      and the indigenous Calabrian population (5.25%) differs significantly. Moreover,
      the Albanians do not show the protoanomalous phenotype. The small sample size of
      Grecanicans does not permit an evaluation of mean CB frequency. Thus, from the
      perspective of CB, the Calabria region may be considered a mixture of "genetic
      isolates" reflecting its historical, sociocultural, demographic, and genetic
      features. Am. J. Hum. Biol. 12:17-24, 2000. Copyright 2000 Wiley-Liss, Inc.

PMID- 11534001
TI  - Sensitivity and specificity of the body mass index to assess low percent body fat
      in African women.
AB  - The objective of this study was to evaluate the ability of the body mass index
      (BMI, kg/m(2)) to reflect low percent body fat (%BF) in a population with a
      rather mild but widespread prevalence of low BMI. A sample of 586 women was
      studied in the Plateau Koukouya, a rural area of the Republic of Congo, Central
      Africa. Percent BF was estimated from bioelectrical impedance (BIA). BIA
      parameters were assumed to reflect lean body mass. The correlation between %BF
      and BMI was high (r = 0.84; P < 0.001). Low %BF or low BIA parameters were
      defined as the first quartile of the distribution. Sensitivity, specificity,
      positive and negative predictive value of BMI <18.5, an accepted international
      cutoff for thinness, in relation to %BF was 58.5%, 93.6%, 75.4%, and 87.1%,
      respectively. A continuous sensitivity/specificity analysis (receiver operator
      characteristic [ROC] curves) for characterizing low %BF or low BIA parameters was
      done for a large range of BMI values. ROC curve analysis for %BF suggested that
      an acceptable trade-off between sensitivity (89.8%) and specificity (77.9%)
      occurred at a BMI of 19.7 kg/m(2). However, the positive predictive value was low
      (57.6%). For the prediction of low BIA parameters, results were similar, showing
      moderate sensitivity and high specificity for BMI <18.5, a cutoff point of BMI =
      19.6, and low positive predictive values (<48%). The data suggest that BMI was
      not a good predictor of low %BF. This is consistent with the assumption of a
      decrease in both fat and fat free body mass in cases of low BMI. Am. J. Hum.
      Biol. 12:25-31, 2000. Copyright 2000 Wiley-Liss, Inc.

PMID- 11534002
TI  - Cross-trait familial resemblance for resting blood pressure and body composition
      and fat distribution: The HERITAGE family study.
AB  - Cross-trait familial resemblance between resting blood pressure (BP) and body
      composition and fat distribution was examined in 98 Caucasian families
      participating in the HERITAGE Family Study by using a multivariate familial
      correlation model assessing both intraindividual and interindividual cross-trait
      correlations. The 520 family members were sedentary at baseline examination, and
      both resting systolic (SBP) and diastolic (DBP) BP were cross-analyzed with each
      of the following 10 indications of body composition and fat distribution: percent
      body fat (%BF), abdominal visceral fat (AVF), body mass index (BMI), fat-free
      mass (FFM), fat mass (FM), sum of eight skinfolds (SF), total abdominal fat
      (TAF), ratio of trunk-to-extremity skinfolds (TER), waist circumference (WAIST),
      ratio of waist-to-hip circumferences (WHR). Five of the variables were also
      corrected for fat mass (AVFf, TAFf, TERf, WAISTf, WHRf) to index these measures
      independent of total degree of adiposity. In general, the results suggested
      strictly intraindividual cross-trait resemblance, with occasional spouse cross
      trait resemblance, but few or no sibling or parent-offspring cross-trait
      correlations. This pattern is largely consistent with nongenetic specific
      environmental determinants for the BP-body composition and fat distribution
      covariation, with possibly some common environmental influence between spouses
      and negligible genetic effects. The only findings suggesting any familial cross
      trait resemblance were significant sibling correlations for DBP-FFM and DBP-WHR,
      although the parent-offspring correlation was not significant. These findings
      suggest that the observed BP-body composition and fat distribution cross-trait
      correlations in these sedentary families are probably not due to multifactorial
      effects such as polygenic and/or common familial environmental effects. Whether
      or not other factors such as nonadditive effects are involved warrants further
      investigation using other methods. Am. J. Hum. Biol. 12:32-41, 2000. Copyright
      2000 Wiley-Liss, Inc.

PMID- 11534003
TI  - Growth and nutritional status of rural South African children 3-10 years old: The
      Ellisras growth study.
AB  - This study presents cross-sectional data from an ongoing mixed-longitudinal study
      of growth of rural children from Ellisras, South Africa. The physical growth and
      nutritional status of 1,335 children (684 boys, 651 girls), 3-10 years of age,
      was determined using standard anthropometric techniques. Weight-for-age, height
      for-age, and weight-for-height were expressed as Z-scores of the NHANES I and II
      or NCHS reference sample. A Z-score of less than -2 was used as the cut-off point
      to determine the prevalence of stunting and wasting. Mean heights increased
      parallel to the 50(th) centile up to 6 years of age, thereafter both sexes
      diverged from the NHANES reference by approximately 0.5 cm per year. Mean weights
      followed a more consistent pattern from 3-7 years for both sexes, which was
      parallel to just below the 10(th) centile, but diverged between 8 and 10 years of
      age. Z-scores of weight-for-height in both sexes varied between -1 to -2
      throughout the age range and BMI values were lower than the 5(th) centile of
      NHANES, indicating a significant amount of wasting within the sample. The sample
      exhibited a high prevalence of stunting, rising from less than 10% at 7 years to
      more than 30% by 10 years of age. Increments of the mean heights and weights
      indicate that the effects of stress may be a gradually accumulating process and
      that the growth increments of these children became increasingly poor in contrast
      to those of the reference sample. Since stunting in childhood is permanent, it
      may lead to a loss of physical work capacity in adulthood. Therefore, further
      investigation of the cause of poor growth among these rural children is
      imperative. Am. J. Hum. Biol. 12:42-49, 2000. Copyright 2000 Wiley-Liss, Inc.

PMID- 11534005
TI  - Statistical effects of varying sample sizes on the precision of percentile
      estimates.
AB  - The present study evaluates the precision of outlying percentile estimates, with
      age- and sex-associated variations and facilitates decisions needed to revise the
      current NCHS 1977 Growth Charts with regard to 1) the inclusion of 3(rd) and
      97(th) percentiles and 2) the selection of survey data for the construction of
      the revised growth charts. Simulation was performed to obtain data with
      distribution characteristics similar to those of The Third National Health and
      Nutritional Examination Survey (NHANES III) (1988-1991) data. NHANES III consists
      of a two-phase, 6-year, complex stratified multistage probability cluster, cross
      sectional survey conducted from 1988 through 1994 to represent the US
      noninstitutionalized population. Phase I of the survey consisted of 679 boys and
      622 girls in age groups 3, 8, 13, and 18 years. Weight and stature, the body mass
      index (BMI) (weight/stature(2); kg/m(2)) was calculated. The results show that 1)
      the precision of the percentile estimates is greater for stature than for weight
      and BMI, 2) percentiles during the pubertal period are less precise than those
      during the prepubertal and postpubertal periods for weight and BMI but there is
      little difference for stature, and 3) percentile estimates are more precise for
      girls than boys for weight and BMI, but not for stature. The present findings
      suggest that pooling of NHANES III and earlier National Center for Health
      Statistics (NCHS) survey data is necessary to achieve reasonable precision for
      the 3(rd) and 97(th) percentile estimates. Am. J. Hum. Biol. 12:64-74, 2000.
      Copyright 2000 Wiley-Liss, Inc.

PMID- 11534006
TI  - Basal metabolic adaptation of the Evenki reindeer herders of Central Siberia.
AB  - Previous research has suggested that basal metabolic rates (BMRs of indigenous
      circumpolar populations are elevated, perhaps as an adaptation to chronic, severe
      cold stress. This study examines variation in BMR among indigenous (Evenki) and
      nonindigenous (Russian immigrant) populations living in Central Siberia to
      determine: 1) whether the Evenki show evidence of increased metabolic rates, and
      2) whether the metabolic responses of the Evenki are different from those of the
      recent Russian migrants ("controls"). BMRs were measured among 58 Evenki (19 men,
      39 women) and 24 Russian (8 men, 16 women) adults (18-56 years of age) from three
      Siberian villages. Measured BMRs were compared to those predicted based on body
      weight and body SA (Consolazio et al., 1963; Schofield, 1985a,b). BMRs per unit
      weight and FFM were similar in Evenki and Russian men, whereas Evenki women had
      higher BMRs than their Russian peers. Relative to the Schofield (body weight)
      norms, Evenki men and women and Russian men all showed modest elevations in BMR,
      whereas Russian women had lower than expected BMRs. Compared to the Consolazio
      (surface area) estimates, both Evenki men and women showed significant elevations
      in BMR. Russian men also showed higher than expected BMRs, while those of Russian
      women were slightly below predicted levels. Age-related declines in BMR were
      evident among the women of both ethnic groups, but not among the men.
      Additionally, residence location was an important predictor of metabolic
      variation in the Evenki, with those of the more traditional village showing
      greater elevations in BMR. These results suggest that the Evenki display elevated
      metabolic needs, and this long-term adaptation reflects the interaction of
      genetics and level of acculturation. Am. J. Hum. Biol. 12:75-87, 2000. Copyright
      2000 Wiley-Liss, Inc.

PMID- 11534007
TI  - Pubertal development in Caracas upper-middle-class boys and girls in a
      longitudinal context.
AB  - Changes between pubertal stages (PS) are best analyzed in a longitudinal context.
      A sample of 67 boys and 48 girls from the Caracas Longitudinal Study who
      presented data for the full range of pubertal development: genitalia (G2-G5),
      breast (B2-B5), pubic hair (PH2-PH5), axillary hair (AH2-AH3), and age at
      menarche (AM) during follow-up, were assessed at clinical examination. Medians
      and standard errors for ages at each stage were estimated with the logit method.
      For length of intervals between stages of genitalia, breast, pubic hair and
      axillary hair, intervals B2-M and PH2-M, survival analysis was used according to
      life tables and Cox regression analysis. In boys, G2 occurred at 11.61 years; in
      girls, B2 occurred at 10.35 years and AM at 12.55 years of age. In both sexes,
      length of the intervals PS 2-3 and 3-4 were approximately 1 year, while PS 4-5
      was 1.5 years. Duration of puberty reached 3.7 years in boys (G2-G5) and 3.3
      years in girls (B2-B5); corresponding intervals for PH2-PH5 were 3.1 and 3.0
      years in boys and girls, respectively. B2-AM was 1.8 years (with a range of 0.3
      3.6 years) and PH2-AM was 1.5 years (with a range 0.3-3.5 years). These results
      are useful for screening and monitoring: identifying abnormal pubertal patterns
      in subjects who are advanced or delayed with respect to their peers, together
      with other pubertal events such as age at peak height and weight velocity and
      skeletal age. Am. J. Hum. Biol. 12:88-96, 2000. Copyright 2000 Wiley-Liss, Inc.

PMID- 11534008
TI  - Are social-class differences in stature partly genetic? A hypothesis revisited.
AB  - Twenty-three different, socially homogenous groups of 19-year-old males were
      selected from a total sample of 57,000 Polish conscripts examined in 1986 and in
      1995. Each group consisted of age-mates equated for six criteria of social
      background: 1) maternal and 2) paternal education, 3) maternal and 4) paternal
      occupational status, 5) number of children in the family, and 6) degree of
      urbanization of the subject's locality of residence. Within every one of the 23
      groups, subjects who at the age of 19 years were secondary-school or college
      students, were taller than socially similar peers, who by that age had never
      moved beyond the level of basic vocational school. Thus, a significant
      association exists between an individual's potential for upward social mobility
      and tallness. Such associations must be taken into account when considering the
      origin and nature of the commonly observed taller stature of the upper over the
      lower social strata in present-day industrial societies. Am. J. Hum. Biol. 12:97
      101, 2000. Copyright 2000 Wiley-Liss, Inc.

PMID- 11534009
TI  - Can socioeconomic factors account for "atypical" correlations between timing,
      peak velocity, and intensity of adolescent growth in Taiwanese girls?
AB  - This study uses longitudinal height records of girls in two urban and one rural
      area in Taiwan. Individual height records were modeled with the Preece-Baines
      Model 1 (PB1) function to test two related hypotheses: 1) Taiwanese students who
      experienced a relatively stable, affluent growth environment from an early age,
      as judged from parental education and stability of residence type, will have a
      pattern of correlations for the timing and intensity of the growth spurt similar
      to those of European and American females; and 2) those students whose parents
      gained the wherewithal to move from single-story to multi-story dwellings while
      they were in primary school will have the most atypical patterns. The extent to
      which these and other sociodemographic factors influence pubertal spurt
      velocities and increments of adolescent growth were explored as well using
      multiple regression analyses. Results support the view that rapid socioeconomic
      change in Taiwan influenced the relationship between the timing and intensity of
      adolescent growth in stature. Children in the more stable environments in both
      urban areas had patterns of correlations typical of population samples from
      developed countries. The most atypical correlations in both areas were found
      among those who likely experienced the greatest improvement in socioeconomic
      status during primary school. These represent positive values previously
      unreported in the literature. Differences in amounts of growth, though in accord
      with these patterns, were quite small. Am. J. Hum. Biol. 12:102-117, 2000.
      Copyright 2000 Wiley-Liss, Inc.

PMID- 11534010
TI  - Variability in humeral dimensions in a sample of modern human females:
      Implications for measuring cortical bone loss.
AB  - Using data from a skeletal collection of early 20(th) century humans, this study
      explores characteristics of humeral measurements regarding assessment of gross
      cortical bone loss. The sample consists of 22 probable females, with estimated
      ages ranging from young to older adult and concentrated in middle adulthood.
      Multiple direct measurements reflecting bone quantity, including internal
      cortical bone and medullary cavity thickness and area, as well as external shaft
      and joint surface dimensions, are analyzed in an attempt to ascertain which
      measurement types, sites, and axes are most and least variable. Variability is
      specifically assessed through coefficients of variation and F-ratios. External
      dimensions are generally lower in dispersion than internal measures. Among
      cortical dimensions, percentage cortical area exhibits the least variability. The
      midshaft and distal sites appear substantially comparable in variability. Similar
      overall dispersion is also shown for the anteroposterior and mediolateral
      orientations. Recommendations concerning consistency of measurement and
      effectiveness in revealing cortical bone loss among living subjects and
      archaeological specimens are offered. Am. J. Hum. Biol. 12:118-127, 2000.
      Copyright 2000 Wiley-Liss, Inc.

PMID- 11534011
TI  - Somatotype and angiographically determined atherosclerotic coronary artery
      disease in men.
AB  - The relationship between somatotype and somatotype components with coronary
      artery disease (CAD) and regional adiposity was considered in 58 males (age 60.2
      +/- 9.4 years) undergoing investigative coronary angiography for suspected
      atherosclerotic CAD. Severity of CAD was determined in terms of both the degree
      of stenosis and the anatomical position of the lesions on the coronary arteries
      (myocardial score). Six patients had negative angiographic findings but three of
      these had impaired left ventricular function as determined by left
      ventriculography. The mean (+/-SD) somatotype of the group was 5.7 / 5.6 / 1.2
      (1.7 / 1.4 / 1.0), illustrating a clear dominance of the first two somatotype
      components. Canonical correlation analysis showed that somatotype was not
      significantly related to the angiography results (P > 0.05). However,
      correlations between the somatotype components and the angiography results with
      their respective first canonical variates showed that the somatotype variate was
      one of high mesomorphy and low ectomorphy and the angiography variate was
      essentially one of a high myocardial score. After adjustment for the confounding
      interrelationship among the somatotype components, endomorphy was significantly
      correlated with abdominal circumference (r = 0.65, P < 0.001), the abdomen-to-hip
      ratio (r = 0.53, P < 0.001) and the abdominal sagittal diameter (r = 0.60, P <
      0.001). Mesomorphy was not related to these indicators of android or abdominal
      adiposity following partial adjustment. Ectomorphy was inversely related to the
      indices of general and regional adiposity. This study suggests that adiposity and
      muscularity are important features in terms of increased CAD risk, whereas
      linearity is beneficial. Am. J. Hum. Biol. 12:128-138, 2000. Copyright 2000 Wiley
      Liss, Inc.

PMID- 11534012
TI  - How sexually dimorphic are we? Review and synthesis.
AB  - The belief that Homo sapiens is absolutely dimorphic with the respect to sex
      chromosome composition, gonadal structure, hormone levels, and the structure of
      the internal genital duct systems and external genitalia, derives from the
      platonic ideal that for each sex there is a single, universally correct
      developmental pathway and outcome. We surveyed the medical literature from 1955
      to the present for studies of the frequency of deviation from the ideal male or
      female. We conclude that this frequency may be as high as 2% of live births. The
      frequency of individuals receiving "corrective" genital surgery, however,
      probably runs between 1 and 2 per 1,000 live births (0.1-0.2%). Am. J. Hum. Biol.
      12:151-166, 2000. Copyright 2000 Wiley-Liss, Inc.

PMID- 11534013
TI  - Association of dominant somatotype of men with body structure, function during
      exercise, and nutritional assessment.
AB  - This study examined the hypothesis that somatotype determines body structure,
      functional responses at peak exercise, and nutritional status of 63 men ages 18
      40 years who lived under controlled conditions. Data were grouped by dominant
      somatotype to emphasize differences in body types. Dominant ectomorphs (n = 19)
      had less (P < 0.05) body weight, fat weight, and percent body fat than endomorphs
      (n = 14) and mesomorphs (n = 30). Fat-free weight (FFW), total body potassium
      (TBK), and body cell mass (BCM), normalized for stature, were lower (P < 0.05) in
      the ectomorphs than in the endomorphs and mesomorphs. Comparisons between
      measured and predicted FFW and TBK showed that only the ectomorphs had less (P <
      0.05) FFW and TBK than expected. Although all groups had the same peak power
      output, the ectomorphs had different functional responses during peak exercise.
      Ectomorphs had the greatest respiratory exchange ratio (P < 0.05), ventilatory
      equivalent for oxygen, and end-exercise plasma lactate concentrations (P < 0.05),
      and lowest peak oxygen uptake (L/min; P < 0.05). Nutrient intakes and blood
      biochemical markers of nutritional status were within the range of normal values
      in all groups. Correlations between measures of body structure, function, and
      nutritional status and dominant somatotype components were calculated after
      controlling for the effects of the other two somatotype components. Partial
      correlations were variable, with significant correlations ranging from -0.30 to
      0.87. These data indicate that ectomorphs, as compared to endomorphs and
      mesomorphs, have deficits in FFW and BCM which are associated with differences in
      functional capacity. Am. J. Hum. Biol. 12:167-180, 2000. Published 2000 Wiley
      Liss, Inc.

PMID- 11534014
TI  - Variability of gestational age distributions by sex and ethnicity: An analysis
      using mixture models.
AB  - As an antecedent of birthweight and in its own right, gestational age is an
      important proximate determinant of infant mortality. Recent analyses using
      mixture models of birthweight distributions suggest that substantial
      heterogeneity occurs within a birth cohort even when controlling for sex and
      ethnicity. This article extends the mixture model analysis to gestational age.
      The results indicate that, like birthweight, human gestational age distributions
      are heterogeneous, consisting of two, or perhaps more, subpopulations with
      separate means and variances. The possibility that birthweight and gestational
      age both identify the same underlying subpopulations cannot be rejected.
      Statistical analyses of the sex and ethnic differences indicate that, like
      birthweight, gestational age distributions vary significantly between the sexes
      and among ethnic groups. However, the pattern, and even the direction, of the
      variation often differs between the two indicators of birth outcome. The results
      suggest that a multivariate mixture model that combines birthweight and
      gestational age might be a useful extension of the univariate mixture models. Am.
      J. Hum. Biol. 12:181-191, 2000. Copyright 2000 Wiley-Liss, Inc.

PMID- 11534015
TI  - Field test of self-paced work capacity: Ifugao rice farmers.
AB  - This article reports results of a field test of work capacity on 30 male farmers
      ranging in age from 15-54. It involved a self-paced walk from the valley floor,
      up the mountain wall, and return, with heart rate monitoring. The route was 2.21
      km long with a vertical rise of about 200 m. At its steepest, the grade was about
      34 degrees, requiring long runs of steps cut into the mountain face. The purpose
      of this research was to determine whether biological and behavioral traits of
      individual men help to explain household economic productivity to which they
      contribute. The traits included anthropometry and a new measure of self-paced,
      voluntary work capacity (heart rate x time). Income per productive adult
      increased as did the relative fitness index (heart rate increase above resting x
      min taken to finish the course). However, the number of rice bundles earned per
      family, expected to increase with more fit workers, increased with the number of
      household adults and sitting height (adjusted R(2) = 0.392), but not with self
      paced fitness markers. Am. J. Hum. Biol. 12:192-200, 2000. Copyright 2000 Wiley
      Liss, Inc.

PMID- 11534016
TI  - beta(A) globin gene haplotypes in Mexican Huichols: Genetic relatedness to other
      populations.
AB  - The haplotypes of 97 beta(A) independent chromosomes from a Mexican Huichol
      Native American group were analyzed. The analysis also included 87 beta(A)
      chromosomes from a Mexican Mestizo population previously studied. Among Huichols,
      eight different 5' beta haplotypes (5Hps) were observed, with types 1(+ - - - -),
      13(+ + + - +) and 2(- + + - +) at frequencies of 0.794, 0.093, and 0.041,
      respectively. In Mestizos, 17 5Hps were found, types 1, 3(- + - + +), 2, 5(- + - 
      +) and 9(- - - - -) being the most common at frequencies of 0.391, 0.172, 0.092,
      0.069, and 0.046, respectively. 3' haplotype (3Hps) frequency distributions were
      0.443(+ +), 0.083(+ -), and 0.474(- +) in Huichols and 0.563(+ +), 0.149(+ -),
      and 0.287(- +) in Mestizos. Pairwise comparison for both haplotype distributions
      between the two populations showed significant differences. Pairwise
      distributions of 3Hps for Huichols were compared with nine worldwide populations,
      three African, two Asian, two Melanesian, one Caucasian, and one United States
      Native American. The distributions of the Huichol were different (P < 0.05) from
      all populations except the Native American. Nei's genetic distances showed the
      Huichols to be closer to the Native Americans, followed by Melanesians from
      Vanuatu and Asians; Africans were the farthest. The 5Hp distributions in Mexicans
      were also compared with 23 worldwide populations (including African, Native
      American, Asian, Caucasian, and Pacific Islanders). Huichol distributions were
      different (P < 0.05) from all other populations except Koreans. The Mestizo
      distribution was also different from the others, except three Caucasian groups.
      Nei's genetic distance between the same populations disclosed that the Huichols
      are in relatively close proximity to five out of six Asian populations
      considered. The same analysis with grouped worldwide populations showed Native
      Americans as population closest to the Huichols, followed by Pacific Islanders
      and Asians. Present observations are consistent with an important Asian
      contribution to the Huichol genome in this chromosomal region. Am. J. Hum. Biol.
      12:201-206, 2000. Copyright 2000 Wiley-Liss, Inc.

PMID- 11534017
TI  - Follow-up of participants in the Trois-Rivieres Growth and Development Study:
      Examining their health-related fitness and risk factors as adults.
AB  - The purpose of the study was to examine the effect of daily physical education in
      primary school on some indices of fitness (PWC170/kg, handgrip strength, sit and
      reach flexibility, abdominal muscle endurance, and balance), cardiovascular
      health (lipid profile, waist-to-hip ratio), and anthropometry in the adult years.
      Four subsamples of participants in the Trois-Rivieres Growth and Development
      Study were examined: experimental men (n = 32), experimental women (n = 36),
      control men (n = 30), and control women (n = 35), some 20 years after completion
      of primary school. During 6 years of primary school education, the experimental
      group received 5 h of physical education each week, whereas the control group
      received only the typical Provincial program of a single 40-min period per week.
      Experimental men and women showed a significant advantage over their respective
      control groups on the Flamingo balance test, but scores for the remaining
      physical and health-related fitness tests (PWC170, handgrip strength, total
      cholesterol, LDL-C, HDL-C, Apo B, triglycerides, blood pressures, waist-to-hip
      ratio and percentage of body fat) did not differ between experimental and control
      subjects. It is concluded that participants in a daily physical education program
      during primary school do not display any advantage of physical fitness over
      control subjects as adults. This underlines the necessity of stimulating physical
      functions throughout the lifespan in order to maintain physical fitness. However,
      the better result of experimental subjects on the balance test suggests, perhaps,
      that the school physical education program may have had a more permanent effect
      on some components of motor skills. Am. J. Hum. Biol. 12:207-213, 2000. Copyright
      2000 Wiley-Liss, Inc.

PMID- 11534018
TI  - Adenosine deaminase-acid phosphatase association and the environment: A study in
      a continental Italian population.
AB  - Three hundred fifty newborns from Rome and 351 from Penne were studied in
      continental Italy. Medium high altitude above sea level and cold winters
      characterize the area of Penne, while low altitude and very mild winters
      characterize the area of Rome. An effect of environmental conditions on the
      association between adenosine deaminase (ADA) and acid phosphatase (ACP1),
      previously shown in Sardinia, has been confirmed in continental Italy. When
      compared with expected independent assortment, the proportion of ACP1*A/*A
      carrying the ADA*2 allele is lower than expected in the lowlands and higher than
      expected in highlands. In continental Italy there is an interaction among ACP1
      ADA genotype, season of conception, and locality. The excess of *A/*A newborns
      carrying the ADA*2 allele is present only among those conceived in the first half
      of the year (January-June). Among newborns in Penne conceived in the Spring, the
      proportion of those with *A/*A genotype is increased and these infants show
      decreased intrauterine growth. The present data suggest that ADA and ACP1
      interact during intrauterine life with effects on development and survival and
      that such effects are dependent on local environment and season of conception.
      Am. J. Hum. Biol. 12:214-220, 2000. Copyright 2000 Wiley-Liss, Inc.

PMID- 11534019
TI  - Estimating percentage total body fat and determining subcutaneous adipose tissue
      distribution with a new noninvasive optical device LIPOMETER.
AB  - A newly developed optical device was applied to measure the subcutaneous adipose
      tissue (SAT) thickness of 20 healthy women and 18 healthy men at specified body
      sites. These measurements were used to derive equations to estimate percentage
      total body fat (TBF%). Total body electrical conductivity (TOBEC) was employed as
      a reference method; caliper techniques and measurements of absorbances of
      infrared light in fat versus lean tissue were also compared. The LIPOMETER
      results show good agreement with TOBEC data (r = 0.96). The technique allows the
      precise determination of the distribution of SAT thickness at specified body
      sites. The method also permits the construction of profiles of SAT thicknesses,
      e.g., the profiles are significantly different between women and men. Based on
      the normal profiles of healthy subjects, patients with proven type-2 diabetes
      mellitus were also evaluated. The patients showed significantly different
      profiles. By linear discriminant analysis, classification functions were
      extracted with good predictive accuracy classification of subjects according to
      the presence or absence of type-2 diabetes mellitus. The data suggest that
      measurement of SAT thickness might aid in the diagnosis and/or classification of
      metabolic disorders. Am. J. Hum. Biol. 12:221-230, 2000. Copyright 2000 Wiley
      Liss, Inc.

PMID- 11534020
TI  - Measurement of subcutaneous adipose tissue topography (SAT-Top) by means of a new
      optical device, LIPOMETER, and the evaluation of standard factor coefficients in
      healthy subjects.
AB  - The quantification of obesity in respect to subcutaneous adipose tissue and fat
      distribution is a matter of interest. We recently reported on a new optical
      device, LIPOMETER, and its ability to measure the thickness of subcutaneous
      adipose tissue and its advantages compared with other methods. To describe the
      subcutaneous adipose tissue distribution of the human body in a precise,
      reproducible, and comparable manner, 15 well-defined body sites distributed from
      neck to calf on the right body side were used. This set of sites defines
      subcutaneous adipose tissue topography (SAT-Top). To visualize SAT-Top for
      subjects or groups, special SAT-Top plots were used. Subcutaneous adipose tissue
      distribution can be recognized easily with these techniques. SAT-Top of 590
      healthy men and women was measured. Factor analysis was used to extract the
      essential information from these 590*15 intercorrelated single measurements and
      to provide standard factor coefficients for later applications. As an example of
      how to use the results of factor analysis, the strong SAT-Top deviation of women
      with clinically proven type-2 diabetes mellitus (NIDDM) from healthy controls is
      described. Am. J. Hum. Biol. 12:231-239, 2000. Copyright 2000 Wiley-Liss, Inc.

PMID- 11534021
TI  - Validation of body composition estimates in male and female distance runners
      using estimates from a four-component model.
AB  - This study used estimates of body composition from a four-component model
      (%Fat(d,w,m)) to determine whether the assumed density (D(ffm)) and the
      composition of the fat-free mass (FFM), and estimates of body composition from
      methods based on two- and three-component models are valid in distance runners.
      Measures of body density (D(b)) by underwater weighing, total body water by
      deuterium dilution, and bone mineral by dual-energy X-ray absorptiometry (DXA)
      were obtained in 10 female and 12 male runners and an equal number of controls
      matched for age, height, weight, gender, and ethnicity. D(ffm) of the runners did
      not differ from 1.1 g.cm(-3) or from the controls even though the composition of
      the FFM differed from that assumed. Therefore, percentage of body fat (%Fat) from
      densitometry did not differ from %Fat(d,w,m) in the runners, although individual
      variation was substantial (-5.3 to 3.0% body mass, SD(diff) = 2.1% body mass).
      Three-component model estimates of %Fat from D(b) and body water agreed quite
      closely with %Fat(d,w,m) (x </= 1.6% body mass, SD(diff) = 0.5% body mass),
      whereas those from D(b) and body mineral (x(diff) = 1.6-2.9% body mass, SD(diff)
      = 2.3% body mass) and from DXA (x(diff) = 2.2-4.0% body mass, SD(diff) = 2.1%
      body mass) were less accurate and underestimated %Fat(d,w,m). We conclude that
      D(ffm) does not differ from 1.1 g.cm(-3) and that densitometry is a valid method
      to estimate group mean body composition, but that measurement of D(b) and total
      body water are necessary for accurate individual estimates of body composition in
      male and female distance runners. Am. J. Hum. Biol. 12:301-314, 2000. Copyright
      2000 Wiley-Liss, Inc.

PMID- 11534022
TI  - Quantitative dermatoglyphics and population structure in Northwest India.
AB  - The nature and extent of dermatoglyphic variation in northwest India is examined
      with the help of 28 quantitative variables-20 finger ridge counts and 8 palmar
      pattern ridge counts-among 12 endogamous populations. These populations represent
      the entire spectrum of ethnic and socioeconomic variation of the region and are
      presently distributed in three different states-Rajasthan, Punjab, and Himachal
      Pradesh. Of a total sample of 1,160 adult males, about 100 from each group were
      considered. Multiple discriminant analysis and R-matrix analysis were used to
      derive population relationships and patterns of external gene flow, respectively.
      Published data on genetic markers were reanalyzed to make the comparative
      evaluation of the patterns with reference to dermatoglyphs. Both the discriminant
      analysis and the F(ST) from R-matrix analysis suggest highly significant
      discrimination among the northwestern groups, whether one uses only 20 finger
      ridge count variables or all 28 variables, including the 8 palmar pattern ridge
      counts. The 8 palmar variables add very little to the variation explained by the
      20 finger ridge count variables. F(ST) values suggest that the populations of
      Punjab are most homogeneous and those of Himachal Pradesh most heterogeneous.
      However, the levels of differentiation are similar for dermatoglyphs and genetic
      markers. The pattern of external gene flow as inferred through R-matrix analysis
      is consistent with the breeding and population structure of the groups, although
      genetic markers portray a relatively more realistic picture. Overall, the
      patterns of variation observed in dermatoglyphs and genetic markers are
      consistent with different dimensions of population structure; whereas
      dermatoglyphs conform more to the geographic pattern and less to ethnic
      resemblance, the reverse is true in the case of genetic markers. Am. J. Hum.
      Biol. 12:315-326, 2000. Copyright 2000 Wiley-Liss, Inc.

PMID- 11534023
TI  - Secular change in craniofacial morphology.
AB  - Five craniofacial variables (glabella-occipital length, basion-bregma height,
      maximum cranial breadth, nasion-prosthion height, and bizygomatic breadth) were
      used to examine secular change in morphology from the mid-19(th) century to the
      1970s. The 19(th) century data were obtained from the Terry and Hamann-Todd
      anatomical collections, and the 20(th) century data were obtained from the
      forensic anthropology databank. Data were available for Blacks and Whites of both
      sexes. Secular change was evaluated by regressing cranial variables on year of
      birth. Two analyses were conducted, one using the original variables and one
      using size and shape. Size is defined as the geometric mean of the cranial
      variables, and shape is the ratio of each variable to size. The results show
      remarkable changes in the size and shape of the cranial vault. Vault height
      increases in all groups in both absolute and relative terms. The vault also
      becomes longer and narrower, but these changes are less pronounced. Face changes
      are less than the vault changes, but to the extent that they occur, the face
      becomes narrower and higher. Overall cranial vault size has increased, but shape
      changes are greater than size changes. The magnitude of secular change in vault
      height exceeds that for long bones over a comparable time period, but follows a
      similar course, which suggests that vault height and bone length respond to the
      same forces. Changes in vault dimensions must occur by early childhood because of
      the early development of the vault. Am. J. Hum. Biol. 12:327-338, 2000. Copyright
      2000 Wiley-Liss, Inc.

PMID- 11534024
TI  - Mitochondrial control-region sequence variation in the Corsican population,
      France.
AB  - The mtDNA sequence variation of the hypervariable segment I of the control region
      was studied in 47 unrelated individuals of Corsican origin from Corte (Corsica,
      France). Thirty-one different sequences were identified by 40 variable sites, of
      which five involve transversions. The nucleotide diversity among the sequences
      was estimated as 1.03%. The pairwise difference agreed with the model proposed by
      Rogers and Harpending ([1992] Mol Biol Evol 9:552-569) and appeared bell-shaped,
      with only one peak at 3.71, indicating the occurrence of a single episode of
      demographic expansion roughly 14,443 to 41,584 years ago. From our results it
      seems that the ancestral Corsican population expanded more recently than all
      other studied European populations. Compared to other populations by genetic
      distances and a neighbor-joining tree, Corsicans appear most closely linked to
      the Basques and Sardinians than to other populations. Although the results
      substantiate an east-to-west migration, some problems are evident: 1) the
      estimates of demographic expansion are not in agreement with paleontological
      data; 2) the expansion occurred later than the expansion of the Sardinian
      population; and 3) the genetic affinity between Corsicans, Basques, and
      Sardinians. Answers will need to come from archaeological, paleontological,
      genetic, geological, and climatological observations. Finally, the study of mtDNA
      confirms what had already been shown with classic genetic markers. Am. J. Hum.
      Biol. 12:339-351, 2000. Copyright 2000 Wiley-Liss, Inc.

PMID- 11534025
TI  - Surname frequency and the isonymy structure of Venezuela.
AB  - Isonymy in Venezuela was studied analyzing the surnames of 3.9 million adults 40
      years and older, selected from the register of electors updated in 1991. The
      electors were not differentiated by sex and represented all 22 states of
      Venezuela and its Federal District. The states of Nueva Esparta, an island, and
      Merida, in the Venezuelan Andes, have the highest coefficients of
      microdifferentiation (R(ST)) and of inbreeding due to random isonymy. The states
      of Miranda, Aragua, Carabobo, and the Federal District, which includes the
      capital, Caracas, or are very close to it, had the lowest R(ST) values. The
      weighted averages of Fisher's alpha, a measure of surname abundance, varied by
      state from 43 in Nueva Esparta to 226 in Miranda, with a value of 210 for the
      entire country, much smaller than those observed in Switzerland, Germany, or
      Italy (2,396, 2,855, and 5,855, respectively). The fact that 32% of the total
      Venezuelan sample has only 40 surnames easily accounts for this small alpha. The
      correlation between the Euclidean distance and the log of geographic distance
      between the capital cities of states in km is high and significant (r = 0.78).
      The dendrogram built with the Euclidean distance matrix indicates the presence of
      three main clusters. One is formed by 10 states located in the western-central
      part of the country. The states of Zulia and Falcon join this cluster at a
      distance of 0.54 Euclidean units. A second cluster is formed by Barinas and the
      three Andean states. After combining these two, a third cluster joins them,
      formed by six Eastern states. Finally, the state of Amazonas enters the
      dendrogram at a distance of 0.66 units. Am. J. Hum. Biol. 12:352-362, 2000.
      Copyright 2000 Wiley-Liss, Inc.

PMID- 11534026
TI  - Estimation of maximum increment age in height and weight during adolescence and
      the effect of World War II.
AB  - An attempt was made to estimate the maximum increment age (MIA) in height and
      weight of Japanese boys and girls during the birth years 1893-1990 through the
      published data of the Ministry of Education, Science, Sports and Culture in
      Japan. In cases where the same maximum annual increment occurred in two or three
      successive age classes in a birth year cohort, a new formula (see Eq. 2) was
      developed to estimate the MIA. The existing formula for estimating MIA was
      modified to remove the mathematical deficiency (Eq. 1). Estimated MIA shows an
      overall declining trend, except in birth year cohorts 1934-1951. The effect of
      World War II on MIA was investigated by a dummy variable regression model. On
      average, during the birth years 1934-1951, MIA in height decelerated by 1.35
      years in boys and 0.54 year in girls, while MIA in weight decelerated by 0.95
      year in boys and 0.78 year in girls. Am. J. Hum. Biol. 12:363-370, 2000.
      Copyright 2000 Wiley-Liss, Inc.

PMID- 11534027
TI  - Epidemiological transition in Easter Island (1914-1996).
AB  - This study describes the mortality patterns during the present century (1914
      1996) and investigates the epidemiological transition in a single community,
      Easter Island (Rapanui), the geographically most isolated inhabited island.
      Mortality patterns were reconstructed from civil records and included deaths of
      all island residents. The mean annual number of deaths is 9.3. A steady decline
      in the mortality rate linked to rapid modernization is the most relevant general
      trait. Although a small mortality crisis was detected in 9 years of the period
      studied, there was no significant seasonality in the deaths, possibly due to
      little climatic variation. The most serious sanitary problem was leprosy, endemic
      on the island from the end of the 19(th) century. Sanitary improvements, on one
      hand, and the effective breakdown of isolation, on the other, brought about the
      eradication of leprosy and the beginning of an epidemiological transition. In the
      latter years of the study, there was an increasing prevalence of degenerative
      diseases, connected, in part, with changes in the age structure of the population
      caused by the decline of mortality. A correspondence analysis shows the
      relationships between causes of death and age, and makes clear the different
      incidence of disease by age. The infant mortality rates were lower than in the
      Chilean population. Am. J. Hum. Biol. 12:371-381, 2000. Copyright 2000 Wiley
      Liss, Inc.

PMID- 11534028
TI  - Abnormal allometric size of vital body organs among sudden infant death syndrome
      victims.
AB  - Sudden infant death syndrome (SIDS) victims are difficult to describe physically
      because they seem outwardly indistinguishable in nearly all characteristics from
      infants (alive or dead) of comparable chronological age. Relative (allometric)
      size of vital organ and body weights has not been examined among SIDS victims. In
      the present study, autopsy organ and body weights for 152 SIDS deaths (1-12
      months) were compared with the results of 115 controls that were trauma or
      illness-related death (0.25-12 months). A pattern of abnormal relative size in
      vital organs (brain, heart, liver, and kidney) was revealed. In allometric
      regressions, increase in the weights of the organs relative to total body weight
      among SIDS victims were approximately three times the increase among controls in
      the first year of life. This finding indicates a disturbance of normal patterns
      of vital organ size of SIDS victims that is of unknown etiology. Am. J. Hum.
      Biol. 12:382-387, 2000. Copyright 2000 Wiley-Liss, Inc.

PMID- 11534029
TI  - ROC and CART analysis of subcutaneous adipose tissue topography (SAT-Top) in type
      2 diabetic women and healthy females.
AB  - Women suffering from type-2 diabetes mellitus (NIDDM) show a more android fat
      pattern than healthy females, but to date no exact determination of their fat
      distribution differences exists. Measurements at 15 specified body sites with an
      optical device, the LIPOMETER, provide a subcutaneous adipose tissue topography
      (SAT-Top) of the individual. SAT-Top of 20 female NIDDM patients and 122 healthy
      controls was measured. ROC curve analysis was applied to evaluate the
      discriminative power of each body site and to provide cutoff values. Then a
      classification tree by the CART algorithm was established, showing SAT-Top
      differences between the two groups. Best discriminating results were achieved by
      the neck site (ROC area index = 0.76, sensitivity = 61.3%, specificity = 77.8%),
      the four sites of the thigh (area indices from 0.71 to 0.76), and a linear
      combination of all body sites stemming from a previous factor analysis, which
      provides condensed information of the extremities SAT-Top (area index = 0.80,
      sensitivity = 80.4%, specificity = 64.6%). The results could be improved by a
      summary measure of "android fat pattern" (area index = 0.89, sensitivity = 73.6%,
      specificity =88.3%) and a proportional measure of SAT-distribution, the relative
      neck (area index = 0.84, sensitivity = 83.0%, specificity = 70.5%). Overall, 136
      (95.8%) of the 142 subjects were correctly classified by the classification tree
      (sensitivity = 75%, specificity = 99.2%). Both methods show the expected
      increased upper trunk obesity and decreased lower body obesity of NIDDM women
      compared with healthy females. Am. J. Hum. Biol. 12:388-394, 2000. Copyright 2000
      Wiley-Liss, Inc.

PMID- 11534030
TI  - Familial resemblance in fatness and fat distribution.
AB  - The purpose of the study was to estimate the degree of familial resemblance in
      anthropometric indicators of fatness and fat distribution. The sample consisted
      of 327 Caucasian participants from 102 nuclear families. Indicators of fatness
      included the body mass index (BMI), the sum of six skinfolds (SF6: triceps +
      biceps + medial calf + subscapular + suprailiac + abdominal), and waist
      circumference (WAIST), while indicators of fat distribution included WAIST
      adjusted for BMI (WAIST(ADJ)), the trunk-to-extremity skinfold ratio, adjusted
      for SF6 (TER(ADJ)), and the first principal component of skinfolds, adjusted for
      the mean skinfold of the individual (PC1). A general familial correlation model
      was fit to the data, and a series of nested reduced models were also fit so as to
      test hypotheses about familial resemblance. The hypothesis of no familial
      resemblance (all familial correlations are zero) was rejected for all phenotypes,
      indicating that fatness and fat distribution aggregate within families. For the
      three indicators of fatness (BMI, SF6, and WAIST), the sibling and parent
      offspring correlations were significant. Further, there were no sex or generation
      differences in the familial correlations. For the three indicators of fat
      distribution (TER(ADJ), WAIST(ADJ), and PC1), there was no parent-offspring
      resemblance; sibling resemblance was significant for TER(ADJ) and PC1. Further,
      spouse resemblance was not significant for WAIST(ADJ), but was for TER(ADJ) and
      PC1. For both WAIST(ADJ) and PC1 there were significant sex differences in the
      familial correlations. A combination of models including no sex or generation
      differences and no spouse resemblance was the most parsimonious model for BMI,
      SF6, and TER(ADJ). The environmental model (all correlations equal) was the most
      parsimonious for WAIST, the model of no sibling resemblance was the most
      parsimonious for WAIST(ADJ), and the model of no spousal resemblance was the most
      parsimonious for PC1. Estimates of maximal heritability range from 46-60% for
      fatness and from 29-48% for fat distribution, independent of overall fatness,
      suggesting that in this sample the heritability of fatness is greater than that
      for fat distribution. Further, the pattern of correlations, which generally
      includes no spousal resemblance but significant parent-offspring and sibling
      correlations, suggests the role of genes in explaining at least part of the
      heritability. Am. J. Hum. Biol. 12:395-404, 2000. Copyright 2000 Wiley-Liss, Inc.

PMID- 11534031
TI  - Secular changes in relative leg length in post-war Japan.
AB  - Longitudinal secular changes of height and estimated leg length (ELL) or
      subischial leg length of Japanese boys and girls were investigated using data
      published in "The Statistical Report of the School Health Survey" of the Ministry
      of Education, Science, Sports and Culture, Japan. A significant trend towards
      greater relative leg length (long-leggedness) among Japanese children and youth
      has occurred during the period of about four decades covered by this study. After
      showing a strikingly consistent trend at all age levels between 6 and 17 years
      and a dramatic trend during the birth-year age period 1943-1963, the relative
      growth in leg length has been rapidly slowing or has stopped in both sexes. The
      relative growth of ELL seemed to be fixed after 11 years in boys and 9 years in
      girls. Maximum increment ages (MIA), both in height and ELL, were used as
      estimates of the timing of maximum growth during the adolescent spurt. Regression
      analysis was used to demonstrate the overall trend patterns of MIA in height and
      ELL. After removing autocorrelation effects, MIA for height is accelerated by
      0.03 year in both sexes, while the MIA in ELL is accelerated by 0.03 year in boys
      and 0.01 year in girls. Thus, MIA in ELL in girls is occurring earlier but to a
      smaller extent than in boys. The average maturity difference between boys and
      girls is 2.07 years in height, but 2.83 years in lower extremity length. Am. J.
      Hum. Biol. 12:405-416, 2000. Copyright 2000 Wiley-Liss, Inc.

PMID- 11534032
TI  - Effects of prenatal cocaine exposure and postnatal environment on child
      development.
AB  - Studies on the long-term developmental effects of in utero cocaine exposure are
      few and the small number of studies published do not consider the postnatal
      environment. The present investigation was conducted to quantify the role that
      postnatal environment played compared to prenatal exposure. Four groups of 25
      infants, each assessed at 12 months of age, were included in the study design: 1)
      noncocaine-exposed children residing with their biological parents in low
      socioeconomic environments, 2) cocaine-exposed children living with their
      biological parents in low socioeconomic environments, 3) noncocaine-exposed
      children adopted at birth in middle to upper-middle socioeconomic environments,
      and 4) cocaine-exposed children adopted at birth. Infants were assessed by the
      Uzgiris-Hunt Ordinal Scales of Infant Psychological Development, the Fagan Test
      of Infant Intelligence, and the Infant Monitoring Questionnaire. Height and head
      circumference were measured. Gender and ethnicity were controlled statistically.
      Significant differences were found in cognitive functioning, in fine motor
      development, and in physical growth between control and prenatally cocaine
      exposed children. Adoption enhanced cognitive functioning and fine motor skills
      among infants not exposed to cocaine prenatally, but had no apparent effect on
      infants prenatally exposed to cocaine. Am. J. Hum. Biol. 12:417-428, 2000.
      Copyright 2000 Wiley-Liss, Inc.

PMID- 11534033
TI  - The Barbara Heath Roll somatotype archive.

PMID- 11534034
TI  - Empirical validation of an instrument to measure habitual physical activity in
      youth from Maputo, Mozambique.
AB  - To develop a questionnaire to assess habitual physical activity in Mozambican
      children and youth, a study with school youth of Maputo was done. The study
      included the assessment of usual activities, development of the questionnaire,
      and testing its validity and reliability. The questionnaire was initially based
      on anecdotal observations of the usual activities of this population, then a
      sample of 20 children was observed during 24 h and interviewed the day before
      with a model that asked the subjects about the time spent in each activity.
      Fifteen days later the same students were interviewed with the questionnaire in
      order to test its validity. After another 15 days, the reliability of the
      questionnaire was tested. To score the questionnaire, estimation of metabolic
      equivalents (METS) of the socioculturally specific activities was done. This was
      based on published tables and heart rate monitoring of the children performing
      the activities listed on the questionnaire. Intraclass correlations between time
      observed and time reported ranged form 0.06-0.80, demonstrating limited capacity
      of the children to report time. However, percentage of agreement between the
      observations and the questionnaire concerning activity levels was 83%. It was
      concluded that the questionnaire may be a useful instrument for assessing the
      patterns of physical activity of African youth and for classifying groups
      according to levels of activity. However, it has limited utility for estimating
      energy expenditure. Am. J. Hum. Biol. 12:437-446, 2000. Copyright 2000 Wiley
      Liss, Inc.

PMID- 11534035
TI  - Change in food availability during pregnancy: Is it related to adult sudden death
      from cerebro- and cardiovascular disease in offspring?
AB  - Maternal access to food during pregnancy affects birth weight and other
      characteristics of offspring. It has been suggested that fluctuations in food
      availability during infancy, ranging from plentiful to starvation, may influence
      cerebro-cardiovascular risk factors for the offspring during adult life. This
      study was designed to test the correlation between food availability changes
      during life before birth and adult sudden death from disease. This was a follow
      up study of ancient cohorts in the parish of Skelleftea, Sweden, comprising 7,572
      individuals born between 1805 and 1849 and still alive at age 40. Food
      availability variations in the parish during their prenatal life were ascertained
      from historical sources, the main outcome measures being overall mortality and
      mortality from sudden death in the age range 40-70 years. The risk of sudden
      death was almost doubled for those whose mothers were struck by a poor harvest
      during the early stages of pregnancy, but who experienced a good harvest toward
      the end. Yet almost the same over-risk was evident for the converse case:
      plentiful food supply in early pregnancy followed by a poor harvest toward the
      end. A stable maternal access to food during pregnancy is important for the
      offspring's risk of sudden death from cerebro- and cardiovascular disease as an
      adult. Am. J. Hum. Biol. 12:447-453, 2000. Copyright 2000 Wiley-Liss, Inc.

PMID- 11534036
TI  - Interaction of different hemoglobinopathies in Eastern India with a view to
      establish genotype-phenotype correlation.
AB  - Analysis of the molecular basis of hemoglobinopathies provides an opportunity to
      define genotype-phenotype variations as well as establish the origin of mutation.
      The present study deals with a large cohort of 1,661 cases referred to the
      counseling unit and 889 individuals from random screening of the population of
      Tripura. Characterization of mutation in 291 cases (582 alleles) was performed by
      the PCR-ARMS method using genomic DNA. The haplotype of 56 beta(E) mutation
      bearing chromosomes were identified by the RFLP-PCR method. Genotypes were
      constructed and correlated with hematological and clinical phenotypes. IVS-1nt 5
      (G-->C) mutation was observed as the most frequent mutation, followed by codon 30
      (G-->C). Production of HbE was significantly (P < 0.001) higher in nontransfusion
      dependent Ebeta-thalassemia patients. beta(E) mutation was observed only on four
      haplotypes linked to framework 2. Type 2 haplotype was observed mainly from
      chromosomes of Tripura origin, but none from South Bengal. Homozygous E
      individuals with 1//1 genotype were significantly (P < 0.01) more anemic compared
      to individuals with 2//2 genotype. This work creates a database of
      hemoglobinopathy mutations for the population of Eastern India which will
      facilitate prenatal diagnosis and counseling. Am. J. Hum. Biol. 12:454-459, 2000.
      Copyright 2000 Wiley-Liss, Inc.

PMID- 11534037
TI  - Beard vs. forehead, ten years later.
AB  - Ten years ago (1988), we observed in a sample of 100 men that the area of the
      glabrous skin above the eyebrows was proportional to the area of the hairy skin
      on the cheeks, lips, and chin. Ten to 11 years later, we measured again 39 of the
      former subjects to check longitudinally whether the relationship would still be
      valid. In the group of 39 subjects, the correlation was again significant and the
      regression was practically the same as that obtained in the same sample 10 years
      earlier. This would tend to show that ontogeny follows phylogeny. This results is
      understood as indirect evidence in favor of selective brain cooling in humans.
      Am. J. Hum. Biol. 12:460-464, 2000. Copyright 2000 Wiley-Liss, Inc.

PMID- 11534038
TI  - Helminthiasis and culture change among the Cofan of Ecuador.
AB  - Blood and fecal samples and lifestyle interviews were obtained in August 1996
      from two Cofan villages in Ecuador, Dureno and Zabalo, that are experiencing
      different degrees of acculturation. Dureno's territory has been divided by roads
      and encroached upon by oil companies and colonists, whereas Zabalo, 95 km
      downriver from Dureno, is located in the Cuyabeno Fauna Reserve, a protected
      area. This study examines how culture change affects the prevalence of parasitic
      infections. Fecal samples were examined for helminth eggs to determine
      helminthiasis in each village sample. Seventy-four samples were collected (Dureno
      n = 50; Zabalo n = 24), representing 20% of the population in each village.
      Hemoglobin (Hb) levels and eosinophil counts were determined for all adult
      participants (Dureno n = 39; Zabalo n = 13). Microscopic examination of prepared
      samples revealed ova from two parasitic nematodes: roundworm (Ascaris
      lumbercoides) and hookworm (Ancylostoma duodenale or Necator americanus).
      Roundworm and hookworm infections were higher in Dureno (44% positive) compared
      to Zabalo (17% positive), with infected adults from both villages showing
      eosinophilia. Hb levels were not significantly correlated with the prevalence of
      helminth infections. It appears that the transmission and prevalence of parasitic
      infections within each community is associated with the interaction of
      biological, cultural, and environmental factors. Am. J. Hum. Biol. 12:465-477,
      2000. Copyright 2000 Wiley-Liss, Inc.

PMID- 11534039
TI  - Modernisation and children's blood pressure: On and off the tourist trail in
      Nepal.
AB  - Blood pressure and anthropometric measurements were taken for 231 children
      between 11 and 14 years in the Annapurna area of Central Nepal, a popular tourist
      destination. Children from villages on the tourist trail, whose lifestyles were
      generally more modernised, were compared with children from nearby villages off
      the tourist trail. Indications of greater modernisation on the trail included the
      findings that fathers of children living on the trail were less likely to work as
      farmers than fathers of those off the trail (P = 0.003), and children living on
      the trail were much more likely to have seen television (P < 0.001). Children on
      the tourist trail were taller and heavier (P < 0.001), and had higher body mass
      indices (P = 0.003) and biceps skinfolds (P = 0.005). They also had higher
      diastolic blood pressure than children living off the trail (P = 0.02). The
      differences in weight appeared to account for the effect of living on the trail
      on diastolic blood pressure, since when weight was added to the model it showed a
      significant association with diastolic blood pressure (P = 0.02) and the effect
      of location became nonsignificant. For the biceps skinfold and systolic blood
      pressure, there was a significant sex difference in the effect of living on the
      trail (P = 0.04 and P = 0.05 respectively), such that among girls there were
      greater increases associated with living on the trail than there were among boys.
      The findings suggest that lifestyle changes linked to the development of tourism
      in Nepal are associated from an early age with potentially deleterious changes in
      cardiovascular characteristics and demonstrate that such socioeconomic changes
      can have quite local effects. Am. J. Hum. Biol. 12:478-486, 2000. Copyright 2000
      Wiley-Liss, Inc.

PMID- 11534040
TI  - Daily physical activity and physical fitness from adolescence to adulthood: A
      longitudinal study.
AB  - The stability of physical fitness and physical activity in Flemish males from 18
      to 40 years of age was investigated. In addition, effects of a consistently low
      activity or high-activity level during the same age period on physical fitness
      were studied. The sample consisted of males who were followed longitudinally from
      age 13 to age 18 years, and were remeasured at the ages of 30, 35, and 40 years.
      Complete data about physical fitness and physical activity between 13 and 40
      years were available for 130 subjects. Stability was measured using Pearson
      autocorrelations and simplex models. Multivariate analysis of variance (MANOVA)
      for repeated measurements was used to look for the effects of activity level on
      physical fitness. Simplex models showed higher stability coefficients than
      Pearson correlations, and stability of physical fitness was higher than stability
      of physical activity. Physical fitness showed the highest stability in
      flexibility (r = 0.91 between 18 and 30 years, r = 0.96 for both the 30-35 and 35
      40 ages intervals), while physical activity showed the highest stability during
      work (r between 0.70 and 0.98 for the 5-year intervals). Results from MANOVA
      indicated that for some fitness characteristics the high-active subjects were
      more fit than their low-active peers. Stability of physical activity was higher
      than assumed and, therefore, it is a useful and independent indicator for further
      research. Although possible confounding factors are present (e.g., heredity), a
      higher level of physical activity during work and leisure time on a regular basis
      benefits physical fitness considerably. Am. J. Hum. Biol. 12:487-497, 2000.
      Copyright 2000 Wiley-Liss, Inc.

PMID- 11534041
TI  - Prevalence of obesity among school children in the United Arab Emirates.
AB  - The objective of this study was to investigate the prevalence of obesity among
      schoolchildren in the United Arab Emirates, using the body mass index (BMI) as
      the indicator. The sample included 1,787 males and 2,288 females 6-16 years.
      Physicians and trained nurses measured height and weight, and the BMI (kg/m(2))
      was calculated. The 50(th) centile of the BMI was not different from that for the
      US. Similarly, the height and weight of UAE children approximate the US reference
      data. About 8% of UAE boys and girls have BMI's >/=95(th) percentile of US
      reference values. Using the 85(th) percentile as the criterion, 16.5% and 16.9%
      of males and females, respectively, are classified as overweight. This composite
      figure does not differ from the expected 15% based on reference data. The data
      thus indicate that high levels of obesity are present among UAE children and
      adolescents. These findings have public health implications for this generation
      of UAE youth during their adult years, including heart disease and diabetes,
      because the rate of morbid obesity is approximately twice that expected in
      reference data. Am. J. Hum. Biol. 12:498-502, 2000. Copyright 2000 Wiley-Liss,
      Inc.

PMID- 11534042
TI  - Changes in menarcheal age in girls exposed to war conditions.
AB  - The purpose of this study was to assess changes in mean menarcheal age of girls
      in the city of Sibenik in the period from mid-1980s to the mid-1990s. Sibenik is
      a Dalmatian town which was exposed to hard war conditions in 1991-1995.
      Menarcheal status of Sibenik girls was surveyed three times, in 1981, 1985, and
      1996, and included 720, 1,207, and 1,680 girls, respectively, ages 9.5-16.5
      years. Mean menarcheal age was estimated by the status quo method and application
      of probit analysis. Results show a slight decrease in menarcheal age from 1981 to
      1985 (from 12.97 +/- 0.06 years to 12.87 +/- 0.05), and then a significant
      increase from 12.87 +/- 0.05 years in 1985 to 13.13 +/- 0.10 years in 1996. The
      increase in mean menarcheal age occurred in all socioeconomic groups based on
      parental occupation and number of siblings. In the group of girls whose homes
      were damaged during war, menarche occurred at an average of 13.53 +/- 0.14 years,
      while those who lost a family member experienced menarche at an older mean age,
      13.76 +/- 0.27 years. However, when the girls who experienced personal tragedies
      were excluded the onset of menarche was still later than in girls surveyed in the
      earlier periods. The results suggest that the general reversal in the secular
      trend of menarcheal age in Sibenik girls can be attributed to persistent
      psychological pressures and uncertainties associated with conditions of war. Am.
      J. Hum. Biol. 12:503-508, 2000. Copyright 2000 Wiley-Liss, Inc.

PMID- 11534043
TI  - Population structure of the rural communities on the island of Krk (Croatia): A
      comparison of genetic, cultural, and geographic data.
AB  - The population structure of seven rural communities from the island of Krk
      (Croatia) was studied on the basis of its genetic constitution and genetic
      structure, and different sets of biological (genetic), biocultural (migration),
      cultural (linguistic), and geographic data. Genetic constitution was estimated
      from the allelic frequencies of nine tetranucleotide STR loci, three HLA class I
      loci, five HLA class II loci, and five red blood cell enzyme and serum protein
      loci. Genetic structure was based on coefficients of genetic diversity G(ST) and
      genetic kinship R(ST). Population structure was assessed by the structure of
      mutual relationships among biological, biocultural, cultural, and geographic
      matrices through Mantel's test, or by relationships among biological,
      biocultural, cultural measures of distance and/or similarity, and geographic
      distance with regression analysis of the "isolation by distance" model. One group
      of genetic markers (red blood enzymes, serum proteins, and HLA polymorphisms)
      reflects heterogeneity of the rural communities (a reflection of important
      historical processes and migration patterns), and a second group of genetic
      markers (STR polymorphisms) reflects the currently observed genetic homogeneity
      of the rural population. The positive correlations between the matrices of
      genetic (HLA) and linguistic distances indicate their possible co-evolution under
      conditions of genetic isolation (low gene flow). Furthermore, the negative
      correlations between the matrices of genetic (STR) distances and the migration
      kinship of the second and the third cohort indicate temporal coincidence between
      genetic constitution and structure assessed from STRs and migration patterns in
      the period between 1892 and 1940. Finally, the positive correlations between the
      matrices of genetic (STR) and geographic distances indicate isolation by
      distance. Am. J. Hum. Biol. 12:509-525, 2000. Copyright 2000 Wiley-Liss, Inc.

PMID- 11534044
TI  - Time series analysis of monthly body weight and blood pressures of one man from
      29 to 65 years.
AB  - Time series analysis was carried out on monthly data of body weight and blood
      pressure of one male subject from 29 to 65 years of age by the program Census X
      11 and DECOMP. Body weight increased from 55 kg to 70 kg from 30 to 50 years,
      then decreased to 60 kg afterward. The trend factor of body weight obtained by X
      11 fluctuated markedly even after the removal of seasonal and irregular
      components. The trend factor of systolic blood pressure increased from 120 mmHg
      to 140 mmHg from 40 to 55 years, while diastolic blood pressure increased from 70
      mmHg to 90 mmHg around 40 years of age. These changes were also accompanied by
      many fluctuations. The program DECOMP suggested that the fluctuations observed in
      X-11 were expressed by an autoregressive model. From the viewpoint of the most
      appropriate autoregressive model, it is possible that at younger ages body weight
      and systolic blood pressure may be affected by the values of the previous several
      months. On the other hand, they may be affected by the values of the previous
      month or two at older ages. Spectral analysis was also applied to the
      autoregressive model. Peaks at about 20, 30, or 40 months were observed in body
      weight changes. The pattern of the seasonal factor changed with age in body
      weight and blood pressure. In body weight, the peak appeared in the summer at
      younger ages, but in the autumn or winter at older ages. In blood pressure, the
      peak did not always appear in the winter. Am. J. Hum. Biol. 12:526-541, 2000.
      Copyright 2000 Wiley-Liss, Inc.

PMID- 11534045
TI  - Prevalence and determinants of diabetes mellitus among the Metis of western
      Canada.
AB  - Diabetes and its complications are major contributors to morbidity and mortality
      among Canada's Aboriginal populations. The epidemiology of diabetes among the
      Metis has not yet been investigated. The purpose of this study was to determine
      the prevalence of diabetes among the Metis, to identify diabetes risk factors,
      and to test hypotheses related to diabetes etiology. The source of the data for
      this research was the Aboriginal Peoples Survey (APS), a postcensal survey
      conducted by Statistics Canada in 1991. Study populations included the APS self
      identified Metis and North American Indians of western Canada. Univariate and
      multivariate analyses were done to estimate the prevalence of diabetes and to
      identify diabetes risk factors. Multiple logistic regression was performed to
      test etiological hypotheses regarding the determinants of diabetes. The crude
      prevalence of diabetes among the Metis (6%) was slightly less than that reported
      by North American Indians (7%) and twice the general rate for Canada (3%).
      Diabetes was significantly associated with age, sex, obesity, and level of
      education. The APS dataset was useful in establishing diabetes as a significant
      problem among the Metis. Am. J. Hum. Biol. 12:542-551, 2000. Copyright 2000 Wiley
      Liss, Inc.

PMID- 11534046
TI  - Maternal pelvic size, measured by dual energy X-ray absorptiometry, predicts
      infant birthweight.
AB  - Indicators of infant birthweight are important because infant birthweight is
      related to later health outcomes. This study developed and validated new measures
      of the pelvis from dual energy absorptiometry (DEXA). Predictors of the new
      measures of maternal pelvic size were examined and the pelvic size measures were
      examined as predictors of infant birthweight. Data were drawn from a sample of
      326 women in Hawaii and their 608 infants. The women were 45-60 years old at the
      time of the DEXA bone scan and when they recalled the birthweights of their
      infants. The birthweights were validated with birth certificate data. The women
      were participants in the Early Postmenopausal Interventional Cohort (EPIC) to
      study the effects of alendronate on bone density. Questions on birth histories
      were added to that study. Adolescent milk consumption and age at menarche were
      positively associated with the DEXA hip measure, while Asian ethnicity was
      negatively associated with the hip measure in multiple regression analysis. In
      multiple regression analysis, the hip measure, together with infant gender and
      gestational age predicted infant birthweight; mother's height, weight, and
      ethnicity did not add significantly to the model. DEXA provided measures of the
      pelvis, which varied by ethnicity, hormonal and nutritional variables, and which
      were indicators of infant birthweight. Am. J. Hum. Biol. 12:552-557, 2000.
      Copyright 2000 Wiley-Liss, Inc.

PMID- 11534047
TI  - Effect of sonic driving on maximal aerobic performance.
AB  - The study purpose was to evaluate antecedent binaural stimulation (ABS) on
      maximal aerobic physical performance. Twenty-two healthy, physically active
      subjects, 21-34 years, randomly received one of two preparations for each
      session: 15 min of quiet (BLANK) or percussive sonic driving at 200+ beats per
      minute (bpm) using a recorded compact disc (FSS, Mill Valley, CA) with headphones
      (ABS). Baseline HR, blood pressure (BP), and breathing frequency (f(br)) were
      obtained. During each condition, HR and f(br) were recorded at 3-min intervals.
      The graded maximal treadmill testing was administered immediately postpreparation
      session on separate days, with at least 48 h rest between sessions. There were
      significant differences in the antecedent period means between the two
      conditions, ABS (HR: 70.2 +/- 10.7 bpm; f(br): 18.5 +/- 3.3 br min(-1); BP:
      134.5/87.9 +/- 13.6/9.2 mm Hg) and BLANK (HR: 64.6 +/- 7.9; f(br): 14.3 +/- 2.9;
      BP: 126.7/80.3 +/- 12.1/8.6). Differences were noted for each 3-min interval and
      pre- postantecedent period. The maximal graded exercise test (GXT) results showed
      that there was a small but significant (P < 0.05), increase in maximal VO(2) in
      the ABS (49.8 +/- 6.8 ml. kg(-1). min(-1)) vs. BLANK (46.7 +/- 8.7) conditions.
      Related to that finding was a slight increase (0.5 min) in time to exhaustion (P
      < 0.05). There were no significant differences in HR or RPE (P > 0.05). There may
      be a latency to ABS related to entrainment or imagery-enhanced warm-up. Am. J.
      Hum. Biol. 12:558-565, 2000. Copyright 2000 Wiley-Liss, Inc.

PMID- 11534048
TI  - Erratum.

PMID- 11534049
TI  - Onset of the release of spermatozoa (spermarche) in Chinese male youth.
AB  - Data on the prevalence of the first ejaculating emission for 83,902 Chinese boys
      9 through 18 years were collected using interviews. Median spermarcheal ages
      (MSAs) were calculated by using the status quo data and probit analysis. Subjects
      consisted of 61,812 Han boys from urban and rural areas in 29 provinces, and
      22,090 minority boys from 17 minority ethnic groups. Median spermarcheal ages
      were 14.24 years for urban Han boys and 14.85 years for rural Han boys, and
      ranged from 13.46 to 16.32 years for the 17 minority ethnic groups. The
      differences in MSAs between urban and rural Han boys in each province were
      significant and the correlation between MSA of urban and rural boys in each
      province was high (r = 0.83, P < 0.001). For both urban and rural Han boys, there
      were significant geographic variations. MSAs of boys living in north China were
      generally higher than those living in the south, while those living in the west
      were higher than those living in the east. Variation in MSA may be related to
      ecological conditions in the Chinese Han populations. The different estimates of
      spermarcheal ages with two approaches, periodical urine sample analysis vs.
      interview, and their effect on estimating male puberty are discussed. Am. J. Hum.
      Biol. 12:577-587, 2000. Copyright 2000 Wiley-Liss, Inc.

PMID- 11534050
TI  - Genetic variation at the ApoB 3' HVR minisatellite locus in the Mbenzele Pygmies
      from the Central African Republic.
AB  - This study analyzes the polymorphic minisatellite ApoB 3' HVR in the Mbenzele
      Pygmies from the Central African Republic. A total of 14 alleles was observed,
      with frequencies ranging from 0.020 (19, 21, 27, and 45 repeat unit alleles) to
      0.210 (37 repeat unit allele). Departure from Hardy-Weinberg equilibrium was not
      statistically significant. The estimated heterozygosity was 0.874 +/- 0.016.
      Taking data from the literature into consideration, the results support the
      hypothesis that the Africans are different from non-Africans due to greater ApoB
      3' HVR genetic diversity and a unimodal profile of ApoB 3' HVR allele frequency
      distribution. Interpopulational relationships were also analyzed using an F(ST)
      based genetic distance. The results highlight the similarity between the Mbenzele
      Pygmies and Bantu-speaking groups (Ewondo and Zulu), and the divergence between
      the Mbenzele and San, the two groups which are often considered to be the most
      direct descendants of proto-Africans. Am. J. Hum. Biol. 12:588-592, 2000.
      Copyright 2000 Wiley-Liss, Inc.

PMID- 11534051
TI  - Physical fitness, body fatness, and physical activity: The Amsterdam Growth and
      Health Study.
AB  - The purpose of this study was to examine sex-specific longitudinal relationships
      between physical fitness (cardiopulmonary and neuromotor fitness) and body
      fatness (sum of skinfolds) and to examine the influence of physical activity
      (weighted activity score) on these relationships. The data were obtained from the
      Amsterdam Growth and Health Study (AGHS), an observational longitudinal study of
      98 females and 83 males, with six repeated measurements over a period from 13 to
      27 years of age. The longitudinal relationship between body fatness and physical
      fitness was analyzed using generalized estimating equations (GEE). For each of
      the eight fitness items used as outcome variables, standardized regression
      coefficients were calculated for the relationships with body fatness and for the
      relationships with physical activity with and without correcting for height and
      weight. In all analyses, body fatness was inversely related to running speed,
      standing high jump, leg lift speed, and maximal oxygen uptake. Physical activity
      was positively related to leg lift speed and maximal oxygen uptake, and only in
      females to the standing high jump. Thus, body fatness is inversely related to
      most fitness items, while physical activity is positively related to only several
      fitness items. Further, body fatness and physical activity are independently
      related to physical fitness. Am. J. Hum. Biol. 12:593-599, 2000. Copyright 2000
      Wiley-Liss, Inc.

PMID- 11534052
TI  - Major gene effect on subcutaneous fat distribution in a sedentary population and
      its response to exercise training: The HERITAGE Family Study.
AB  - Complex segregation analysis of baseline subcutaneous fat distribution and the
      change in response to exercise training (post-training minus baseline indices)
      was performed in a sample of 482 individuals from 99 Caucasian families who
      participated in the HERITAGE Family Study. The sum of skinfold (SF) thicknesses
      at eight sites, and the waist and hip circumferences were measured at baseline
      and after completing a 20-week exercise training program. The trunk-to-extremity
      ratio (TER) was calculated by dividing the sum of skinfold thicknesses at four
      trunk sites (subscapular + suprailiac + abdominal + midaxillary) by the sum of
      skinfold thicknesses at four extremity sites (triceps + biceps + medial calf +
      thigh). While SF was used to assess total subcutaneous adiposity, TER and the
      ratio of the waist-to-hip circumferences (WHR) were used to characterize
      subcutaneous fat distribution. Baseline TER and WHR were age-adjusted and age-SF
      adjusted within four sex-by-generation groups. The changes of SF, TER, and WHR in
      response to training were adjusted for age effects alone and for the effects of
      age and baseline values. Baseline SF was influenced by a multifactorial component
      (30%) plus a major effect that may be environmental in origin accounting for 47%
      of the variance. Baseline TER was influenced by a multifactorial component (18%)
      and a major codominant gene (q(2) = 0.10), which accounted for 56% of the
      variance. The major gene effect was independent of total subcutaneous adiposity.
      Baseline WHR was regulated by a major codominant gene (q(2) = 0.15), which
      accounted for 48% of the variance. However, this major gene effect for baseline
      WHR should be interpreted with caution, given the estimates of the tau's under
      the general model. No familial effect was found for the changes in response to
      training for these subcutaneous adiposity and fat distribution phenotypes. Am. J.
      Hum. Biol. 12:600-609, 2000. Copyright 2000 Wiley-Liss, Inc.

PMID- 11534053
TI  - Assessment of skeletal maturity of the hand-wrist and knee: A comparison among
      methods.
AB  - This study evaluated the influence of height growth and nutritional status on
      skeletal maturation of the knee and hand-wrist. Radiographs of 589 subjects (250
      girls and 339 boys) from 2 to 15 years were rated according to Greulich-Pyle, TW
      20 bone and TW-RUS, RWT knee, and FELS hand-wrist methods and a method combining
      FELS and RWT indicators. The subjects were referred to the Genoa University
      Paediatric Department from 1980 to 1987 for short stature, simple obesity, or
      acute diseases. Bone age was closer to chronological age using the RWT knee
      method rather than the hand-wrist methods, while bone age assessed at the hand
      wrist was closely related to height and BMI. When skeletal maturation was
      delayed, Greulich-Pyle, TW-20-bone, TW-RUS, and FELS bone ages tended to be lower
      than RWT knee estimates. Conversely, if maturation was advanced the hand-wrist
      estimates tended to be higher than RWT knee bone ages. The combined estimates are
      close to FELS bone age values. These findings show true intraindividual
      variability of skeletal maturity at the hand-wrist and knee. A certain "laziness"
      in knee maturation seems to be confirmed. Am. J. Hum. Biol. 12:610-615, 2000.
      Copyright 2000 Wiley-Liss, Inc.

PMID- 11534054
TI  - VNTR Locus D1S80: Application to the study of a mixed Venezuelan sample.
AB  - The D1S80 locus in 122 individuals from Maracaibo, Venezuela, was studied to
      verify the genetic relationship of this sample with 32 other reported world
      populations derived from different ethnic groups. All analyses reveal that the
      Venezuelan sample has a main European genetic contribution, followed by
      contribution from Amerindians, and a small contribution of Africans. The
      population of Maracaibo has a high level of heterozygosity, as expected for
      populations with an important level of recent admixture. Am. J. Hum. Biol. 12:616
      622, 2000. Copyright 2000 Wiley-Liss, Inc.

PMID- 11534055
TI  - Similar age-related changes in running performance and growth in adolescent
      monozygotic twins.
AB  - The purpose of this study was to assess the similarities in the pattern of age
      related change in the running performance and physical growth in adolescent
      monozygotic (MZ) twins. The total sample was 70 boys and 100 girls, including 14
      pairs of male and 25 pairs of female MZ twins. Performance of the 50 m dash and
      endurance run (1,500 m for boys and 1,000 m for girls), and stature and body mass
      were measured longitudinally at yearly intervals from 12 to 17 years of age. The
      within-pair resemblance was compared between MZ twin pairs (MZ) and control pairs
      (CP), which were selected from the other subjects matched with each member of MZ
      for the initial values. The within-pair similarity in performance and growth
      curves was quantified by an average Euclidean distance coefficient (d(jk)) and a
      coefficient of shape differences (z(jk)) and a graphical analysis on the d(jk)
      z(jk) coordinate. The time relationship between two curves was assessed by the
      arrangement of the sign of within-pair differences (number of runs, NR). Within
      pair differences of measured value at the first and the last measurements were
      also examined. MZ generally showed smaller d(jk) and z(jk), clustering around the
      origin on the d(jk)-z(jk) coordinate. Frequency of observation of NR = 1, which
      means one member of a pair had consistently larger values than the other, tended
      to be lower in MZ in performance items. Within-pair differences in the last
      measurements were generally greater in CP. It was concluded that MZ twins have
      meaningful similarities in the pattern of age-related changes in running
      performances and physical growth during adolescence. Am. J. Hum. Biol. 12:623
      632, 2000. Copyright 2000 Wiley-Liss, Inc.

PMID- 11534056
TI  - Effect of physical activity on bone mineral density assessed by limb dominance
      across the lifespan.
AB  - Bone mineral density is higher in dominant vs. nondominant limbs, implying that
      the greater use of dominant limbs in everyday activities results in the
      deposition of more bone or that the dominant limb is genetically larger. The
      objective of the present study was to determine whether bone mineral density
      differences between dominant and nondominant arms were greater in older vs.
      younger women. To determine whether this was due to a greater lifetime of
      preferential loading of the dominant arm, differences between dominant and
      nondominant arms were compared to accumulated amounts of physical activities
      which emphasized use of the dominant arm. Bone mineral density of dominant and
      nondominant arms was assessed by dual-energy X-ray absorptiometry in groups of
      younger (n = 35; age = 20.9) and older (n = 53; age = 57.4) women. The difference
      between arms was greater in the older vs. the younger group (5.2% vs. 1.9%,
      respectively, P < 0.01). Within the older group, total lifetime energy
      expenditure during activities emphasizing loading of the dominant arm correlated
      with the bone mineral difference between dominant and nondominant arms (r = 0.47,
      P < 0.01). This implies that a greater lifetime of preferential loading of the
      dominant arm in the older group resulted in a greater difference between arms.
      Am. J. Hum. Biol. 12:633-637, 2000. Copyright 2000 Wiley-Liss, Inc.

PMID- 11534057
TI  - Haplotype and allele frequencies for three genes of the dopaminergic system in
      South American Indians.
AB  - Haplotype and allele frequencies for the dopamine D2 receptor gene (DRD2),
      dopamine D4 receptor gene (DRD4), and dopamine transporter protein gene (SLC6A3)
      were determined in 135 individuals from five Brazilian Indian tribes, and the
      results integrated with those previously presented for this ethnic group. DRD2
      and DRD4 were highly polymorphic. Haplotypes including TaqI A1 at DRD2, and the
      seven repeat allele at DRD4 were the most frequent variants, while the SLC6A3
      locus was monomorphic for the 10 repeat allele in South American Indians. Genetic
      distances and the corresponding neighbor-joining tree indicated a geographic
      dichotomy between North + Central American and South American natives, with the
      exception of the Wai Wai, who live north of the Amazon river and are grouped in
      the northern cluster. G(ST) estimates from these genes vary between 0.05 and 0.11
      for North and South America, respectively, indicating a higher degree of
      differentiation of the latter groups. These results are in accordance with
      previous genetic data on other systems, as well as with the history and
      biodemographical data of South American Indians. Am. J. Hum. Biol. 12:638-645,
      2000. Copyright 2000 Wiley-Liss, Inc.

PMID- 11534058
TI  - Growth studies in Jena, Germany: Changes in sitting height, biacromial and
      bicristal breadth in the past decenniums.
AB  - Changes in sitting height, biacromial and bicristal breadths, and the acromio
      cristal index in school children from Jena between 7 and 14 years of age are
      described. Additionally, a secular comparison of these measurements and the index
      was done, based on the long series of surveys available for schoolchildren in
      Jena. During childhood, sex differences in the dimensions and the index are
      usually slight, but with the onset of the adolescent spurt sex differences are
      clear. Females become relatively broader-hipped and shorter-legged than males,
      with the differences especially marked in the acromio-cristal index. Biacromial
      and bicristal breadths and sitting height increased, on average, between the
      first investigation in 1975 and the survey in 1995. In contrast, the acromio
      cristal index remained almost constant in boys and girls over the observed time,
      with few exceptions. When related to stature, both breadth measurements of the
      trunk have increased, whereas the ratio of sitting height to stature remained
      constant in most age groups between 1975 and 1995. Am. J. Hum. Biol. 12:646-654,
      2000. Copyright 2000 Wiley-Liss, Inc.

PMID- 11534059
TI  - Cardiovascular risk factors of migrants in Port Moresby from the highlands and
      island villages, Papua New Guinea.
AB  - This study examined cardiovascular disease (CVD) risk factors, i.e., obesity,
      blood pressures, and serum lipoproteins and apoproteins, in relation to
      sociocultural characteristics in two rural-urban migrant populations (n = 173
      adult males and females) in Port Moresby, the capital of Papua New Guinea. Tari
      migrants from the highlands and Balopa migrants from the islands differ
      genetically. More importantly, the lifestyle of the latter is more Westernized
      than that of the former in both Port Moresby and their homelands. The results
      demonstrate that CVD risk factors vary markedly among the origin/sex groups and
      that the length of stay in Port Moresby on CVD risk factors was significant only
      in Balopa males, most of whom had professional or skilled full-time jobs and were
      considered to have more stress. This study identified different CVD risk factors
      in the migrant groups: obesity or fatness for the Balopa migrants, and serum
      lipoproteins and apoproteins, particularly lipoprotein(a), for the Tari migrants.
      Am. J. Hum. Biol. 12:655-664, 2000. Copyright 2000 Wiley-Liss, Inc.

PMID- 11534060
TI  - Morphological growth of Han boys and girls born and raised near sea level and at
      high altitude in western China.
AB  - This study compares the morphological characteristics of Han children,
      adolescents, and young adults who were born at 250 m near Beijing and at three
      high altitudes in Qinghai Province, Peoples Republic of China (3,200 m, 3,800 m,
      and 4,300 m). From ages 6 through 15, Han children growing up at high altitudes
      are significantly shorter, lighter, have less fat, and are less muscular than Han
      children growing up at low altitude. However, older adolescents and young adults
      show no such altitude differences. Younger adolescents and children in this study
      were all born after the government economic reforms of 1978. These reforms had a
      greater impact on the growth of children in and around large cities than on those
      in more remote areas. Therefore, the altitude differences in size among Han
      children ages 15 and younger may be a consequence of regional variation in health
      and nutrition, rather than due to the influence of hypoxia. There are no altitude
      related differences in thorax dimensions among Han children, adolescents, or
      young adults. This suggests that hypoxia does not affect the thorax growth of Han
      children. Am. J. Hum. Biol. 12:665-681, 2000. Copyright 2000 Wiley-Liss, Inc.

PMID- 11534061
TI  - Maternal height, pregnancy weight gain, and birthweight.
AB  - The Institute of Medicine recommends that short women gain less weight during
      pregnancy than taller women in order to reduce the risk of high birthweight,
      which can lead to feto-pelvic disproportion. This recommendation, however, is
      based on clinical judgment rather than on epidemiologic evidence, as few studies
      have examined the relationships between maternal height, pregnancy weight gain,
      and infant birthweight. Our objective was to determine whether maternal height is
      an independent risk factor for infant birthweight and to assess whether maternal
      height modifies the effect of pregnancy weight gain on infant birthweight. We
      examined the relationship between maternal height and infant birthweight in a
      multi-ethnic cohort of 8,870 women with uncomplicated pregnancies who delivered
      singleton infants at the University of California, San Francisco, 1980-1990.
      Using multiple linear regression, we modeled the contribution of height and
      weight gain to birthweight in four different ethnic groups. Increasing maternal
      height was significantly and positively associated with infant birthweight in
      White, Black, and Asian women, but not Hispanic women. The relationship between
      pregnancy weight gain and infant birthweight was not modified by maternal height.
      Am. J. Hum. Biol. 12:682-687, 2000. Copyright 2000 Wiley-Liss, Inc.

PMID- 11534062
TI  - Acid phosphatase locus 1 (ACP1): Possible relationship of allelic variation to
      body size and human population adaptation to thermal stress-A theoretical
      perspective.
AB  - The acid phosphatase locus 1 (ACP1) codes for a low molecular weight
      phosphotyrosine protein phosphatase that has the important action of
      dephosphorylating tyrosine phosphorylated proteins and peptides and a second
      important role in modulating flavin cofactor levels and the activity of flavo
      enzymes. These functions significantly influence cell division, differentiation,
      and growth. Two alleles (ACP1*A and ACP1*B) reach polymorphic frequencies at the
      ACP1 locus in all human populations, while the ACP1*C and ACP1*R alleles reach
      polymorphic frequencies in restricted geographical regions. The worldwide
      distribution of these alleles, and data from several clinical studies, strongly
      suggest that the ACP1 locus functions to modulate growth and that selection at
      this locus is a component of the selective processes influencing body mass and
      human population adaptation to thermal stress. The ACP1*A allele reaches highest
      frequencies at extreme latitudes and appears to be associated with maximizing
      body mass and adaptation to cold stress, whereas the ACP1*B allele reaches
      highest frequencies in tropical and subtropical environments and appears to be
      associated with minimizing body mass and adaptation to heat stress. The high
      frequency of the ACP1*C allele at northern latitudes, where ACP1*A allele
      frequencies are elevated, may be a mechanism for limiting fetal and maternal
      complications associated with fetal macrosomia and adult obesity in populations
      where protein and calorie intake are relatively high. Am. J. Hum. Biol. 12:688
      701, 2000. Copyright 2000 Wiley-Liss, Inc.

PMID- 11534063
TI  - Secular trends for takeoff and maximum adolescent growth for eight decades of
      Japanese cohort data.
AB  - The presence of secular trends in the onset or takeoff of the adolescent growth
      spurt and subsequent adolescent growth of Japanese boys and girls were
      investigated using data published in "The Statistical Report of the School Health
      Survey" by the Ministry of Education, Science, Sports and Culture, Japan. An
      optimum kernel regression method was used to derive the biological parameters of
      the adolescent growth curve. An increasing trend in height at takeoff (i.e.,
      height at the onset of the adolescent growth spurt) and height at peak height
      velocity (PHV) among Japanese children was evident during the 8 decades covered
      in this study. Age at PHV (i.e., the timing of the maximum adolescent growth) for
      each sex has decreased. Age at takeoff (i.e., the timing of the onset of the
      adolescent growth spurt) has decreased in boys during this century, but was
      almost constant in girls at about 7.8 years of age. Moreover, the interval
      between age at takeoff and age at PHV in girls has gradually decreased over this
      century. Since the birth year 1915, velocity at takeoff for girls was markedly
      greater than that for boys, whereas peak height velocity for girls was
      significantly less than that for boys (P < 0.05). Am. J. Hum. Biol. 12:702-712,
      2000. Copyright 2000 Wiley-Liss, Inc.

PMID- 11534064
TI  - Prevalence of NIDDM in Mexicans with paraphyletic and polyphyletic surnames.
AB  - It has been hypothesized that the greater prevalence of non-insulin-dependent
      diabetes mellitus (NIDDM) in Mexicans may be related to their greater degree of
      Amerindian genetic admixture (AGA). The aim of this unmatched case-control study
      was to correlate the prevalence of NIDDM with AGA in 10 Mexican Mestizo
      populations non-randomly selected by surname. A sample of 1,699 unrelated
      persons, >44 years and residing in the state of Nuevo Leon, was selected on the
      basis of paraphyletic or polyphyletic surnames and interviewed in the Instituto
      Mexicano del Seguro Social (IMSS). All subjects received a medical examination,
      and diabetes was diagnosed on the basis of World Health Organization criteria.
      Three genetic marker systems were analyzed, and the percentage of AGA was
      calculated. Logistic regression analysis was performed with the prevalence as the
      dependent variable and sex and surname as the independent variables. The Spearman
      rank-order correlation analysis was calculated between the age-adjusted
      prevalence (45-75+ years) and AGA. The correlation revealed a pattern of
      increasing prevalence of NIDDM with increasing Amerindian ancestry by surname.
      Am. J. Hum. Biol. 12:721-728, 2000. Copyright 2000 Wiley-Liss, Inc.

PMID- 11534065
TI  - Effect of a change in selection year on success in male soccer players.
AB  - Since 1997 and following the guidelines of the International Football
      Association, the Belgian Soccer Federation has used January 1st as the start of
      the selection year. Previously, August 1 was the start. This shift prompted an
      investigation of changes in birth-date distributions throughout youth categories
      for 1996-1997 compared to the 1997-1998 competitive years. Birth dates were
      considered for national youth league players, ages 10-12, 12-14, 14-16, and 16-18
      years. Kolmogorov Smirnov tests assessed differences between observed and
      expected birth-date distributions. Regression analyses examined the relationship
      between month of birth and number of participants both before and after the
      August to January shift. Results indicated that from 1996 to 1997, youth players
      born from January to March (the early part of the new selection year) were more
      likely to be identified as "talented" and to be exposed to higher levels of
      coaching. In comparison, players born late in the new selection year (August to
      October) were assessed as "talented" in significantly lower proportions. Specific
      suggestions are presented to reduce the relative age effect. Am. J. Hum. Biol.
      12:729-735, 2000. Copyright 2000 Wiley-Liss, Inc.

PMID- 11534066
TI  - Modeling the influence of settlement structure on the spread of influenza among
      communities.
AB  - Several factors play critical roles in the geographic spread of infectious
      diseases, including the movement of people between communities and the social and
      economic structure of groups of communities. A mathematical model has been
      developed to examine the individual and shared impact of these factors. This
      model was applied to the spread of the 1918-1919 influenza epidemic in three
      Aboriginal communities in central Canada. Previously published results from
      simulations of the model used parameter estimates for mobility patterns that were
      derived from historical documents from the study communities, especially Hudson's
      Bay Company post journals. We have termed this model the Frontier pattern. In
      this paper we extend that work to consider the consequences of three additional
      travel scenarios, which represent idealized trade and travel relationships
      between different communities. The three patterns include (a) the Central
      Marketplace scenario, an idealization of relations between a central community
      and its satellites in which a single central community satisfies all needs of the
      satellite communities; (b) the Sister Towns scenario, which allows travel among
      all communities and overemphasizes communication between satellites so that the
      ramifications of small town interactions are easier to observe; and (c) the
      Circuit scenario, which represents a hypothetical trade network that is a series
      of unidirectional dyad relationships linking all communities within a region.
      Results from simulations of the four mobility patterns are compared to assess the
      potential impact different social and economic relationships among communities
      may have had on the geographic spread of the 1918 influenza epidemic in central
      Canada and in other regions. These results reinforce conclusions that show that
      variation in patterns of mobility significantly influences the timing of epidemic
      peaks but only minimally alters the number of cases within a community. In
      addition, comparisons of the different models indicate that a central location in
      the social and political hierarchy of a region may be more important in
      influencing patterns of epidemic spread than just a central location with regard
      to travel patterns. Furthermore, who was actually travelling and where they were
      travelling had important consequences for epidemic spread. Am. J. Hum. Biol.
      12:736-748, 2000. Copyright 2000 Wiley-Liss, Inc.

PMID- 11534067
TI  - Cardiac dynamics during upright cycle exercise in boys.
AB  - Insight into the cardiac responses to exercise necessitates an understanding of
      both physiological data and cardiac dimensional changes. This study was designed
      to assess cardiovascular alterations during progressive upright cycle exercise in
      ten healthy 10-12-year-old boys. Doppler echocardiography was used to estimate
      stroke volume, and 2-dimensional echocardiography was used to evaluate changes in
      left ventricular systolic and diastolic dimensions. Test-retest reproducibility
      was high for both techniques. Mean peak stroke index and cardiac index values
      were 62 +/- 12 ml m(-2) and 11.79 + 2.62 L min(-1) m(-2), respectively. Stroke
      volume rose by 40% over resting values with early exercise (50 watt work load),
      but beyond moderate intensities (approximately 50% VO(2)max) little change was
      seen. The left ventricular diastolic dimension rose slightly at the onset of
      exercise and then declined slowly. A progressive and more precipitous decline was
      observed in systolic dimension, resulting in an increase in shortening fraction
      from 29% to 47%. This was accompanied by a dramatic fall in peripheral vascular
      resistance from 13.9 to 8.0 units at the onset of exercise. These findings
      suggest a close matching of increases in heart rate and systemic venous return
      and imply a significant role of peripheral pump function in the circulatory
      responses to exercise in children. The cardiac dynamics observed in this study
      mimic those previously described in adult subjects. Am. J. Hum. Biol. 12:749-757,
      2000. Copyright 2000 Wiley-Liss, Inc.

PMID- 11534068
TI  - Seasonal ecology and nutritional status of women and children in a Tanzanian
      pastoral community.
AB  - Anthropometric dimensions for 180 women and 347 individual children (0-18 years)
      from a seminomadic population of Datoga pastoralists living in the Eyasi and
      Yaeda basins of northern Tanzania are used to assess the nutritional status of
      the population and the magnitude and prevalence of changes between late wet
      season and late dry season sampling periods (1989-1991). Results reveal high
      prevalence of undernutrition among both women and children. Almost one-half of
      all women were chronically energy deficient (BMI < 18.5) and were estimated to
      have very low fat stores. Moderate seasonal decreases in fat stores were observed
      in longitudinal, and also inferred in cross-sectional, samples of the women. The
      decreases were more marked among lactating individuals. Almost one-half of all
      children showed evidence of growth retardation due to undernutrition. There was
      some limited evidence of decreased adiposity among children in the dry period
      relative to the wet period. Although drier ecological conditions are associated
      with decreased fat stores among both women and children, the change is of small
      magnitude. Am. J. Hum. Biol. 12:758-781, 2000. Copyright 2000 Wiley-Liss, Inc.

PMID- 11534069
TI  - Anthropometric changes in urban Sardinian children 7 to 10 years between 1975
      1976 and 1996.
AB  - This study is a comparison of several anthropometric variables in school children
      of the same age (7-10 years) and sex measured in two primary schools in Cagliari
      (Sardinia, Italy) at an interval of 20 years (1996 vs. 1975-1976). For both males
      and females of each age-class, there are significant differences in the following
      dimensions: weight, stature, estimated lower limb length, biacromial breadth,
      xiphoid chest circumference, xiphoid chest depth, and bicristal breadth, and also
      in relative sitting height, cephalic index, and facial index. The means of the
      relative sitting height, cephalic, and facial indexes are higher in the children
      measured in 1975-1976 than in those measured in 1996. There are no significant
      differences in sitting height and arm length. In addition, the estimated BMIs of
      the 1975-1976 sample are, on average, lower than those of the 1996 sample. The
      results suggest that urban Sardinian children sampled in 1996 are generally
      taller, heavier, and larger and have a longer head and wider face than their
      peers of 20 years earlier. The increase in stature is due more to an increase in
      lower limb length than in sitting height. Am J. Hum. Biol. 12:782-791, 2000.
      Copyright 2000 Wiley-Liss, Inc.

PMID- 11534070
TI  - Culture change and stress in Western Samoan youth: Methodological issues in the
      cross-cultural study of stress and immune function.
AB  - This study was designed to pursue three objectives: 1) investigate the impact of
      culture change on children and adolescents in Western Samoa; 2) introduce a cross
      cultural perspective to studies of psychosocial stress and immune function; and
      3) evaluate the utility of minimally invasive methods for assessing immune
      function. Seven hundred sixty individuals between the ages of 4 and 20 years were
      recruited from three distinct geographic regions within Western Samoa that differ
      in degree of westernization. Finger prick samples of whole blood were collected
      from each individual and analyzed for antibodies against the Epstein-Barr virus
      (EBV; an indirect marker of cell-mediated immune function) and C-reactive protein
      (a nonspecific marker of current infection). After controlling for age, sex, and
      current infection, EBV antibody levels were significantly elevated in urban Apia
      and rural Upolu, indicating lower levels of cell-mediated immune function. The
      results suggest a higher degree of psychosocial stress in these regions, possibly
      due to exposure to westernizing influences. Am. J. Hum. Biol. 12:792-802, 2000.
      Copyright 2000 Wiley-Liss, Inc.

PMID- 11534071
TI  - Relationship between different subcutaneous adipose tissue layers, fat mass, and
      leptin in response to short-term energy restriction in obese girls.
AB  - This study addresses whether the expected relationship of 15 specified
      subcutaneous adipose tissue layers (SAT layers) from 1-neck to 15-calf and body
      fat mass (FM) with leptin was influenced by a weight-loss program. In 30 obese
      girls (10 prepubertal, 15 pubertal, and 5 late/postpubertal) SAT layers were
      measured by means of the optical device Lipometer. Fat mass (FM) was estimated
      indirectly by means of bioelectrical impedance. Leptin and insulin were
      determined by means of radioimmunoassays. All measurements were performed before
      (pre) and after (post) 3 weeks of low-caloric diet and physical training. At the
      beginning of the study, there were significant correlations for all estimates of
      adiposity and leptin (0.67 to 0.79; P < 0.0001). Five SAT layers from the upper
      body and the trunk (0.48 to 0.67; P < 0.01) but none from the abdominal region
      and lower extremities were correlated with leptin. FM together with SAT layers 4
      upper back and 8-lower abdomen (negative slope) explained 79% of the variation in
      pre leptin values (P < 0.0001). The weight-loss program significantly reduced
      leptin (P < 0.0001), insulin (P = 0.04), estimates of adiposity (P < 0.0001), and
      SAT layers 4-upper back (P = 0.0006), 11-front thigh, 13-rear thigh, and 14-inner
      thigh (P between <0.03 and <0.01). Although significant, the reductions in the
      four SAT layers were small. Estimated fat-free mass was significantly increased
      after three weeks (P < 0.05). Changes in SAT layers from the upper extremities
      and from the trunk were inversely correlated to the decrease in leptin (P between
      <0.05 and <0.001). Initial leptin was the best correlate of the decrease in
      leptin (adj. R(2) = 0.815; P < 0.0001). However, when only changes in adiposity
      and insulin were considered in the regression model, changes in insulin
      contributed to the fall in leptin (adj. R(2) = 0.23; P = 0.004). When changes in
      SAT layers were added to the model, changes in SAT layers 2-triceps and 10-hip
      (negative slopes) contributed to the decrease in leptin (adj. R(2) = 0.48; P <
      0.0001). After weight loss, correlations between estimates of post adiposity and
      post leptin (0.40, P = 0.01 to 0.57, P = 0.0005) were lower compared with pre
      values. SAT layers 4-upper back and 3-biceps contributed independently to post
      leptin values (adj. R(2) = 0.50; P < 0.0001). It is suggested that fat mass and
      SAT layers from the upper body are the main determinants of leptin in obese girls
      before weight loss. The diet and sports intervention program reduced leptin
      independent of the reduction in adiposity. The distribution of subcutaneous fat
      might be a stable correlate of circulating leptin after a short-term reduction in
      energy intake. Am. J. Hum. Biol. 12:803-813, 2000. Copyright 2000 Wiley-Liss,
      Inc.

PMID- 11534072
TI  - Longitudinal assessment of hormonal and physical alterations during normal
      puberty in boys. VI. Modeling of growth velocity, mean growth hormone (GH mean),
      and serum testosterone (T) concentrations.
AB  - The growth and hormonal status of 23 prepubertal and early pubertal normally
      growing boys were evaluated for at least 6 years as they entered and progressed
      through puberty. Each subject was observed during a 24-hr hospital admission
      approximately every 4 months. Standing height was measured upon arising. At the
      same time an early morning (0600hr) serum level of testosterone was obtained. A
      mean growth hormone level was determined from a pool of equal quantities of serum
      from 72 samples obtained every 20 min for 24 hr. The early morning testosterone
      level was used as an index of pubertal status. The effect of the chronological
      age, mean growth hormone, and testosterone levels on the growth velocity was
      investigated. In addition to age, the interaction between the mean growth hormone
      level and testosterone concentration has a significant effect on the velocity of
      growth. Several nonlinear models were explored to describe growth velocity, mean
      growth hormone level, and testosterone concentration in terms of chronological
      age of each subject. Models used were chosen for simplicity, interpretability of
      the model itself and its parameters, and the ability to estimate (and then test)
      the parameters. Unknown parameters of the model were estimated using ordinary
      least squares (OLS), which minimizes the L(2) norm of the observed and the
      predicted values. The L(2) norm may be unduly influenced by outlying observations
      which commonly occur in many biological data sets. Hence, in addition to the OLS
      estimators, the least absolute deviation (LAD) estimator which minimizes the L(1)
      norm of the observed and the predicted values was also considered. Typically, the
      LAD estimators are more robust than OLS estimators. From a clinical point of view
      it may be important to know the "normal" values of growth velocity, mean growth
      hormone level, and testosterone at a given age during puberty. For this reason
      population models for each of these variables along with their 90% confidence
      regions were developed. These will permit identification of those children who
      are outside the boundaries of normal growth for the purpose of evaluation for the
      etiology of the deviation. Am. J. Hum. Biol. 12:814-824, 2000. Copyright 2000
      Wiley-Liss, Inc.

PMID- 11534073
TI  - Influence of dietary quality on the growth of highland and coastal Ecuadorian
      children.
AB  - This study examines variation in dietary patterns and its influence on physical
      growth among children under 60 months of age from rural households of highland
      and coastal Ecuador. Differences in subsistence ecology between the regions
      appear to influence infant and early childhood feeding patterns. Coastal children
      are weaned significantly earlier than their highland counterparts (median +/- SE
      = 15.9 +/- 1.7 vs. 24.7 +/- 3.4 months) and have a weaning/supplemental diet that
      contains significantly more animal foods. In both regions, growth retardation is
      most severe among infants (<12 months), with growth rates being poorer in the
      highlands than on the coast. Linear growth rates among coastal infants are
      positively correlated with intakes of animal energy and animal protein, whereas
      among highland children energy intake from supplemental/weaning foods is
      negatively correlated with linear growth. These divergent patterns appear to be a
      consequence of the differences in nutrient density of the weaning/supplemental
      diets. Among the coastal infants, higher quality, nutrient dense foods augment
      breast milk and contribute to better growth rates. In contrast, among the
      highland infants the more filling, less nutrient dense foods appear to be
      replacing breast milk, and thus compromising growth status. In the older cohorts
      (i.e., "weaning age" children: 12.0-35.9 months, and completely weaned children:
      36.0-59.9 months), linear growth rates stabilize with little evidence of "catch
      up" growth in either region. Improved weight gain, however, is seen among the
      highland children, and is correlated with the nutritional intake (i.e., energy,
      total protein, and animal protein) from weaning foods. Overall, marked growth
      stunting is seen in both regions, but is more pronounced in the highland
      children. These high levels of stunting are largely established in the first 12
      months of life. Greater growth retardation among the highland children appears to
      reflect the influence of hypoxia as well as the lower nutrient density of weaning
      foods in that region. Am. J. Hum. Biol. 12:825-837, 2000. Copyright 2000 Wiley
      Liss Inc.

PMID- 11534074
TI  - Proceedings of the Human Biology Association 25(th) Annual Meeting, April 10-12,
      2000, Adam's Mark Hotel, San Antonio, Texas.

PMID- 11534075
TI  - Maternal self-administration of oral analgesia after Caesarean section.

PMID- 11534076
TI  - Subcutaneous cyclizine.

PMID- 11534077
TI  - Incompatibility of prochlorperizine and ketoprofen.

PMID- 11534078
TI  - Before or after general anaesthesia?

PMID- 11534080
TI  - Combined spinal-epidurals and epidural top-ups 1.

PMID- 11534079
TI  - Fetal acidosis, spinal anaesthesia and phenylephrine.

PMID- 11534081
TI  - Combined spinal-epidurals and epidural top-ups 2.

PMID- 11534082
TI  - Combined spinal-epidurals and epidural top-ups 3.

PMID- 11534085
TI  - PCEA or PACE.

PMID- 11534084
TI  - The hazards of car cleaning and a novel approach to airway control.

PMID- 11534086
TI  - Wrong ECG leads.

PMID- 11534087
TI  - Helicopter transfer of the critically ill and required standards of training.

PMID- 11534088
TI  - Transient fixation on a non-native language associated with anaesthesia.

PMID- 11534089
TI  - Postoperative instructions.

PMID- 11534090
TI  - Myocardial infarction with creatine kinase genetic aberration.

PMID- 11534092
TI  - 'Teaching grandma to suck eggs'

PMID- 11534091
TI  - Patient compliance with pre-operative day case instructions.

PMID- 11534093
TI  - [Randomized controlled clinical trial: example of scientific rigour applied to
      benefit patients].

PMID- 11534094
TI  - Sex differences in rat heart. Different patterns of catalytically active creatine
      kinase isoenzymes.
AB  - OBJECTIVES: We hypothesized that the anaerobic ATP synthesis mediated by the
      creatine kinase/phosphocreatine (CK/PCr) system is sexually dimorphic during
      maturation and aging of the rat heart. BACKGROUND: Gender-related morphological
      and functional differences in cardiovascular aging seem to explain the greater
      longevity of mammalian females, including women. MATERIAL AND METHODS: By means
      of heart CK specific activity and cytosolic CK isoenzyme analyses we studied 46
      male and female Wistar rats of similar weight divided in groups of 200, 250, and
      300 g of body weight. RESULTS: No sex differences were observed in heart weight
      and post 27,000 x g heart protein content at any studied weight. Heart/body
      weight ratios did not show any significant gender difference along the study.
      Differences of heart CK specific activity were found only at 257 +/- 6 g of rat
      body weight due to a decrease of the male enzyme activity. The female heart
      showed a larger variety of cytosolic CK isoenzymes at any studied weight. Heavily
      catalytically stained BB-CK type cytosolic isoenzymes were consistently found in
      the heart of rats of either sex at the studied weights, contrarily to the
      accepted view of CK tissue specificity. CONCLUSIONS: In this work, significant
      gender differences were mainly found in the patterns and number of catalytical
      cytosolic CK cardiac isoforms. Regarding the alternate anaerobic mechanism of ATP
      production, these differences may explain in part the sex differential
      susceptibility to hemodynamic compromise in response to cardiovascular stress, in
      favor of females.

PMID- 11534095
TI  - [Simultaneous assessment of myocardial perfusion and ventricular function using
      thallium-201 at rest/Tc-99m tetrofosmin at effort with single-photon emission
      computerized tomography, synchronized with electrocardiogram (synchronized
      SPECT). Initial experience in Latin America].
AB  - Gated SPECT is a useful technique to evaluate myocardial perfusion, wall motion
      abnormalities and wall thickening. There is not published experience in Latin
      America using dual isotope rest Thallium-201/stress Tc-99m Tetrofosmin Gated
      SPECT. METHOD: We studied 27 patients with coronary artery disease. Coronary
      angiography was performed in all the patients. We used an injection at rest of 3
      mCi of Thallium-201 followed by stress and the administration of 15 mCi of
      Tetrofosmin and Gated SPECT acquisition. Five days after, the patients were
      injected with 20 mCi of Sestamibi at stress, with a second Gated SPECT
      acquisition. Perfusion data were analyzed using 20 SPECT segment analysis. To
      study the wall motion, we divided the heart in 29 segments and every segment was
      scored using a 4 points scale (3 = normal, 2 = mild hipokinesia, 1 = severe
      hipokinesia, 0 = akinesia). RESULTS: The perfusion and wall motion segmental
      score agreement between stress Tc-99m tetrofosmin and stress Tc-99m sestamibi
      were 97% and 84% respectively. CONCLUSIONS: Rest Thailium-201/stress Tc-99m
      Tetrofosmin Dual isotope Gated SPECT technique is a good protocol to assess
      simultaneous myocardial perfusion and wall motion. There is a good agreement of
      the results with the use of rest Thallium-201/stress Tc-99m Sestamibi Dual
      isotope Gated SPECT study.

PMID- 11534096
TI  - [Helical computerized tomography of the thorax in the diagnosis of unresolved
      chronic pulmonary thromboembolism].
AB  - We assessed the diagnostic usefulness of helical CT scan of the thorax in the
      setting of chronic thromboembolic pulmonary hypertension by prospectively
      comparing the results of helical CT scan to those of the pulmonary angiogram
      (gold standard). We studied 40 patients with diagnosis of pulmonary hypertension
      of diverse etiology (mean age: 40.7 +/- 12 y.o.; mean systolic pulmonary artery
      pressure: 91 +/- 33 mmHg)). Thirty of these patients fulfilled the diagnostic
      criteria of chronic thromboembolic pulmonary hypertension and the other ten were
      used as controls. Diagnosis in control patients included: primary pulmonary
      hypertension (4); patent ductus arteriosus (2); atrial septal defect (1);
      rheumatic valve disease (1); ischemic heart disease (1); and acute pulmonary
      embolism (1). Both helical CT scan and pulmonary angiogram were part of the
      routine diagnostic work up of these patients, and were, performed and interpreted
      almost simultaneously (within one week) by a different group of investigators in
      a blind manner. Only the diagnostic accuracy of the method regarding central
      (major arteries) vascular lesions was evaluated. Helical CT scan had an overall
      sensitivity of 100% (29/29), and a specificity of 91% (10/11). Positive
      predictive and negative predictive values were 96.6% (29/30) and 100% (10/10),
      respectively. Overall diagnostic accuracy was 97.5% (39/40). We conclude that
      helical CT scan of the thorax is an excellent alternative approach for the
      diagnosis of major arteries lesions in the setting of chronic thromboembolic
      pulmonary hypertension.

PMID- 11534097
TI  - [Percutaneous occlusion of patent ductus arteriosus with Rashkind device. 4-year
      follow-up].
AB  - We present the results and follow up of ductus arteriosus closure with the
      Rashkind device. Sixty-six devices were implanted in 63 patients, 41 women and 22
      men, with a mean age of 8.2 years. We determined the diameter of the duct, the
      presence or absence of immediate residual leak at 3 months, 6 months, 1 year, and
      every year of follow-up by ecocardiography. The hemodynamic determinations
      showed: type A morphology in 49, type C in 7 and type E in 7; with a mean
      diameter of 4.2 +/- 1.4 mm (range of 2.3 to 8.7 mm) and a Qp/Qs 2.2 +/- 1.5
      (range 0.7 to 8.6). Forty-five 17 mm devices and 18 of 12 mm were used. The
      incidence of immediate residual leak was 65% (n-41); at 24 hrs. Post-procedure
      was 31.7% (n-20) and at one year 7.9% (n-5). Three patients with persistent leak
      had implantation of a second Rashkind device and one more patient an endovascular
      coil, the other patient is waiting for a second occlusor. Minor complications
      occurred in 15.8% (n-10). Results show an occlusion rate at 24 hrs of 68% and at
      one year of 92%; no patient presented migration of the device, hemolysis or
      obstruction of the pulmonary artery branches. We consider that occlusion of the
      ductus arteriosus with the Rashkind device is a safe and effective option for the
      treatment of this pathology.

PMID- 11534098
TI  - [Efficacy of clopidogrel as ADP-dependent platelet aggregation inhibitor. Study
      on individuals with coronary artery disease].
AB  - Acetyl-salicylic acid inhibits thromboxane A2 production and reduces the risk of
      vascular occlusive events by 20 to 25%. Ticlopidine inhibits ADP-dependent
      platelet aggregation and reduces the same risk by 30 to 35%, but produces some
      adverse effects. Clopidogrel is a ticlopidin-derived antiplatelet-drug, with the
      same mechanism of action; reduces the expression of the glycoprotein IIb/IIIa,
      the fibrinogen receptor on the platelet surface. Clopidogrel has the same
      clinical efficacy of ticlopidin and lowers the incidence of adverse effects. In
      this study, we evaluated the effects of one daily dosis of 75 mg of clopidogrel
      on platelet function in 33 subjects with coronary artery disease. Before
      treatment and after the 6th and 12th week, the following parameters were
      evaluated: 5 microM-ADP and 20 micrograms/mL collagen-induced platelet
      aggregation, bleeding time and fibrinogen concentration. In basal and in the 6th
      and 12th week samples, ADP-induced platelet aggregation was 90.7% +/- 13.2, 54.6%
      +/- 23.2 and 49.2% +/- 23.7 respectively, that represents a significant reduction
      of 38.6% and 44.4%. Reduction of collagen-induced platelet aggregation was not
      significative. Plasmatic fibrinogen did not suffer variation during treatment.
      Bleeding time was significant prolonged from 4.1 minutes to 15.4 and 14.6 minutes
      (3.7-3.5 times compared with the test before treatment). There were no
      haemorrhagic complications, only digestive discomfort in fewer than 3% of
      patients. We concluded that clopidogrel is a safe and efficacious drug for
      patients, it efficiently reduces ADP-induced platelet aggregation and prolongs
      bleeding time.

PMID- 11534099
TI  - [Myocardial infarction caused by cold beverage drinking after strenuous physical
      exercise].
AB  - A case of acute myocardial infarction in a 36 years old patient is presented.
      Maleness was male, as the only mayor coronary risk factor. He had myocardial
      infarction associated with ingestion of cold beverage after strenuous physical
      exercise. A coronariographic study was done postmyocardial infarction, which
      showed a mild obstruction of the LAD. The most likely cause of the coronary event
      in this case is coronary spasm and atherosclerosis. A review of the literature on
      this subject is made.

PMID- 11534100
TI  - [Immediate results in percutaneous mitral valvuloplasty with the Nucleus
      balloon].
AB  - We present the immediate results of mitral valvuloplasty in 10 patients using
      Nucleus balloon. Several publications show highly successful results obtained
      with the Inoue balloon and double balloon technique. There are no publications of
      Nucleus balloon. We consider that this device could offer several advantages
      according to its physical and technical characteristics. We performed the
      procedure in 10 female patients, with severe mitral valve stenosis, with an
      average age of 44.8 years (23-70) and an average Wilkins score of 7.5 (6-9),
      using a combined technique. The increase in mitral valve area with Gorlin
      equation was 1.03 +/- .13 to 2.6 +/- .67 cm2, the decrease in transmitral
      gradient from 15 +/- 4.1 to 3.42 +/- 2.6 mm Hg, and decrease in systolic
      pulmonary pressure from 54.1 +/- 18.8 to 24.9 +/- 5.1 mm Hg. One patient
      developed grade I mitral insufficiency after the procedure, and another non
      significant interatrial shunt. CONCLUSIONS: Good results are obtained with this
      balloon, the valvuloplasty technique is more simple than with double balloon, it
      is much cheaper than Inoue balloon and we consider it could be useful in
      moderately calcified valves.

PMID- 11534101
TI  - [Anomalous connection of inferior vena cava to left atrium: infrequent entity
      that can be a diagnosis and surgical challenge].
AB  - This is the diagnostic experiences as well as the surgical mode of treatment used
      in a 31 years old women suffering diversion of the inferior vena cava into the
      left atrium associated with atrial septal defect. The patient had been previously
      studied and operated thrice under conventional circumstances at different
      institutions in order to solve the septal defect. The hemodynamic solution had
      not been reached due to a missing pathological definition. The cineangiogram
      through the saphenous vein specified the left atrium form the inferior vena cava.
      Some considerations are made on the surgical methods used for the fourth
      operation, and in regard of the fact that the patient refused blood transfusion
      because of religious convictions (Jehova Witness).

PMID- 11534102
TI  - [Assessment of ventricular function with nuclear cardiology. Part II: clinical
      applications].

PMID- 11534103
TI  - [When was modern science born? Homage to the memory of Professor Arturo
      Rosenblueth at his birth centennial].
AB  - The Renaissance savants essentially repelled the scholastic translations and
      commentaries of the ancient writings. Nevertheless they did not reach a modern
      vision of the experimental science. Moreover, the education at the universities
      was not credited for the science's development. In fact, the academic training of
      students was rather precarious. The first professional associations, such as the
      "Royal College of Physicians" of London, were not any better. Regarding hermetic
      influence on the Renaissance thought, the cultured and philosophical reformed
      magic (the so called white magic) was the equivalent of science at the time. Once
      the animistic universe, operated by magic, is transformed into the mathematical
      universe, operated by mechanics, the era of science came into being. This
      movement began during the post-Renaissance age and gradually progressed following
      the physical-mathematical orientation of Galileo and his pupils: Borelli,
      Fabrizi, Santorio, Harvey, etc. They initiated the physiological studies and
      introduced the quantitative method into the research field. Harvey's circulatory
      doctrine was the first adequate explication of an organic phenomenon and a
      starting point for the way toward experimental physiology. However the English
      physician did not leave completely the pre-scientific era, as can be inferred
      from his monography on animals reproduction. In this work, some points suggesting
      the birth of modern scientific reasoning alternate with confused, vague and
      capricious assertions. In fact, the modern science did not arise suddenly, but
      was elaborated and sustained slowly starting from the XVII century: the Galileo's
      century.

PMID- 11534104
TI  - [Simplified determination of di (2-ethylhexyl) phthalate (DEHP) and mono- (2
      ethylhexyl) phthalate (MEHP) in blood and organs of the rat administered DEHP].

PMID- 11534105
TI  - [Present condition of health information control and attitudes of occupational
      health professionals in collecting and utilizing health information in
      workplaces].
AB  - Since the Labor Safety and Health Law of Japan provides that the employer is
      responsible for taking custody of personal information obtained in periodic
      health examinations, we are anxious about infringement of privacy. This study was
      conducted to investigate the present condition of health information control in
      each workplace and attitudes of occupational health professionals in collecting
      and utilizing personal health information by means of self-administered mail
      questionnaires. The numbers of respondents were a total of 549 (physicians: 237,
      public health nurses: 175, nurses 122, others & unknown: 15). The major results
      were as follows. 1. Percentage of workplaces in which only health professionals
      can know personal health data from periodic health examinations was 24%
      altogether, but it was 39% in large workplaces where full-time occupational
      physicians were working. 2. More than half of the respondents were of the opinion
      that the results of routine health activities could be presented in academic
      conferences unconditionally or under comprehensive approval of the representative
      of each workplace. 3. About a half of the respondents believed that it was
      necessary to consider the intention of each examinee in utilizing blood specimen
      collected at health examinations for research purposes, even though personal
      identification had been erased. 4. There were many differences among types of
      occupation or age groups in the attitude to changing the procedure for health
      examination. And it was the majority opinion that personal health data provided
      to the employer should be the minimum in order to protect individual benefits. 5.
      The proportion of physicians who felt it necessity to ask about the occupational
      history at the employment health examination was significantly higher than that
      of public health nurses. 6. When a disease was discovered, there were great
      differences among types of disease in the attitude to give the name or condition
      of the disease to the employer without the consent of the patient or his family.
      In view of these results, we feel that occupational health professionals are in a
      dilemma in introducing modern ideas which lay stress on privacy into the Japanese
      occupational health care system which is still operating on the basis of
      traditional paternalism.

PMID- 11534106
TI  - [Development of novel genotoxicity assays by genetic engineering methods].
AB  - Novel genotoxicity assays have been developed to efficiently detect the
      genotoxicity of various environmental chemicals, and to evaluate the potential
      hazards to man. Salmonella typhimurium strains harboring plasmids carrying the
      genes encoding drug metabolizing enzymes, such as acetyl Co-A O
      acetyltransferase, or the strains lacking DNA repair enzymes, such as O6
      methylguanine DNA methyltransferase, are highly sensitive to the mutagenicity of
      particular classes of mutagens. Thus, they are widely used for the efficient
      detection of genotoxicity of complex mixtures. Transgenic mice, named gpt delta,
      have been established for the detection and molecular analysis of mutations in
      various organs of rodents induced by chemicals. Future perspective of the
      genotoxicity assays using genetically engineered organisms is discussed.

PMID- 11534107
TI  - [Studies on procedure for sample preparation of ellagic acid in several kinds of
      foodstuffs].
AB  - A sample preparation for ellagic acid in several kinds of foodstuffs, which is
      included in the List of Existing Food Additives as natural antioxidants in Japan,
      functioning as an antioxidant, was studied. The solid samples were refluxed with
      methanol, and then the extract was refined using a solid-phase cartridge. The
      liquid samples were directly pretreated by solid-phase extraction. On the other
      hand, test solutions for cooking oils and fats were inapplicable to solid-phase
      extraction in this work, because the recovery tests from samples spiked with
      ellagic acid gave low recoveries. Consequently, they were prepared by modified
      frozen method using methanol or acetonitrile-2-propanol-ethanol (2:1:1). The
      recoveries from tested foodstuffs spiked with ellagic acid (50 micrograms/g) were
      75.2-96.9%. The limits of quantification for ellagic acid were 0.05 microgram/g
      by the proposed method.

PMID- 11534108
TI  - [Validation of simple analytical equipment for arsenic].
AB  - In order to improve the arsenic test method, we investigated the effect of
      temperature, solar light and masking ions on that test method. As the results, we
      found that the solar light gave the big damage to the colored reaction on the
      method. In addition, on comparing the improved method with the arsenic test
      method of Merckoquant kit by using the water containing 0.01 ppm arsenic as the
      Japanese guideline for the drinking water, the improved method gave the better
      analytical value than Merckoquant kit that was not sufficiently determined.

PMID- 11534109
TI  - [The status of NIHS Information and Computing Infrastructure (NICI)].
AB  - From 1999 to 2000, NIHS Information and Computing Infrastructure (NICI) were
      newly renovated. The purposes of the renovation are (1) the improvement of the
      communication for business works in NIHS, (2) supporting for the research, (3)
      supporting for the administration work. The Internet connection speed was
      upgraded from 256 Kbps to 1.5 Mbps. The high quality network sever machines and
      database server machines were installed. The large-scale software systems were
      renewed their versions. Four experimental stations for medical plants at
      Hokkaido, Izu, Wakayama and Tanegashima connected to NIHS at Tokyo or Osaka
      branch by ISDN. We describe the providing information on NIHS home page, and how
      to utilize NICI for our research and official works.

PMID- 11534110
TI  - [Development of research support environment for molecular pharmacology and
      toxicology].
AB  - The Chem-Bio Informatics division has developed the institute-wide computer
      network which is connected to the Internet via IMnet (Inter Ministry Network)
      sponsored by the Government. We call the network and associated information and
      computing infrastructure as NICI, the NIHS Information and Computing
      Infrastructure. The primary goal of NICI is to provide general communication
      environment such as e-mails, and the second goal is to provide WWW environment.
      Accomplishing these two goals the division is now challenging to develop
      information and computing environment that directly supports pharmaceutical and
      toxicological research. The prototype of this environment which consists of
      various chemical and biomolecular databases and computing tools has been
      developed under the name of MOBI-DICS. The concept and vision on how to extend
      the prototype to institute-wide infrastructure was discussed.

PMID- 11534111
TI  - [What we can learn on risk assessment of chemicals from the Concise International
      Chemical Assessment Document (CICAD) Project].
AB  - IPCS (the International Programme on Chemical Safety) has launched a new project
      on the Concise International Chemical Assessment Document (CICAD) as one of its
      major targets, which is to assess health and ecological risk from exposure to
      toxic chemicals in the environment through international collaboration. In this
      project, the author and others successfully established a framework in fulfilling
      ambitious aims of developing concise, but useful risk assessment documents on
      chemicals, while assuring credibility and efficiency in the process, and
      incorporating new ideas from ever developing risk assessment methodology and
      related sciences. This combination of usefulness in the outputs, the credibility
      and efficiency in the process, and the flexibility in the ideas reflecting
      scientific progress, shows a good example of what we should do in improving our
      risk assessment in this country and developing assessment documents.

PMID- 11534112
TI  - [First drafts of the Environmental Health Criteria (EHC) circulated for comments
      by IPCS in 1999.4-2000.3].
AB  - Summaries of the first draft of Environmental Health Criteria (EHC), which were
      circulated for comments by IPCS in the period of 1999.4-2000.3, are presented.
      EHC drafts on 2 compounds were received in this period.

PMID- 11534113
TI  - [Studies on rejected food blue no. 1 (Brilliant Blue FCF) aluminum lake].
AB  - One of the brilliant blue FCF aluminum lakes (B-1Als) in the official inspection
      of coal-tar dyes in fiscal year 1999 was rejected. The results of tests of the
      rejected sample were submitted to JSFA-VII except for a violet sub-spot by paper
      chromatography. Its visual spectrum had same lambda max 630 nm as B-1 standard
      and a very small shoulder at 580 nm in comparing to B-1 standard. HPLCs detected
      at 625 nm of subsidiary dyes and 580 nm were performed on the rejected sample of
      B-1Al. A sub-V in HPLCs of th sample which eluted at 37.6 min had its relative
      peak area of 7.9% at 580 nm and 0.24% at 625 nm, and its peak ratio (at 580 nm/at
      625 nm) was extremely large. Consequently, it was presumed that the sub-V in
      those HPLCs corresponded to the violet sub-spot in paper chromatography.

PMID- 11534114
TI  - [Estimated production by the official inspection of coal-tar dyes (including dye
      aluminum lakes) in fiscal year 1999].
AB  - There were 260 official inspections of coal-tar dyes and their lakes in fiscal
      year 1999, and 259 of the lots qualified, one of the 8 samples of Food Blue No. 1
      aluminum lakes was rejected. The quantity of coal-tar dyes that passed inspection
      in Japan in fiscal year 1999 reached 151.9 tons. Coal-tar dye production is
      estimated by month and by manufacturer. The food coal-tar dye produced in the
      largest quantity was Food Yellow No. 4, accounting for 44.2% during this period.

PMID- 11534115
TI  - [Thiamine Hydrochloride Solution Reference Standard (Control 991) of National
      Institute of Health Sciences].
AB  - The raw material of thiamine hydrochloride solution was examined for preparation
      of the "Thiamine Hydrochloride Solution Reference Standard (Control 991)". The
      analytical data obtained were: assay by HPLC, 101.0%; spectrophotometric assay,
      100.4%. Based on the above results, the raw material was authorized as the
      Thiamine Hydrochloride Solution Reference Standard (Control 991) of the National
      Institute of Health Sciences.

PMID- 11534116
TI  - [Tocopherol Acetate Reference Standard (Control 001) of National Institute of
      Health Sciences].
AB  - The raw material of tocopherol acetate was examined for the preparation of the
      "Tocopherol Acetate Reference Standard (Control 001)". Analytical data obtained
      were: IR spectrum, same as that of the Tocopherol Acetate Reference Standard
      (Control 974); specific absorbance, E/cm% (284 nm) = 43.7; thin-layer
      chromatography, no impurities were detected until 50 micrograms of the loaded raw
      material; high-performance liquid chromatography (HPLC), total amount of
      impurities estimated to be less than 0.6%; assay by HPLC, 101.7%. Based on the
      above results, the raw material was authorized as the Japanese Pharmacopoeia
      Reference Standard (Control 001).

PMID- 11534117
TI  - [Tocopherol Reference Standard (Control 001) of National Institute of Health
      Sciences].
AB  - The raw material of tocopherol was tested for the preparation of "Tocopherol
      Reference Standard (Control 991)". Analytical data obtained were: IR spectrum,
      same as the Tocopherol Reference Standard (Control 941); specific absorbance,
      E/cm% (292 nm) = 72.9; thin-layer chromatography, no impurities were detected
      until 50.0 micrograms; high-performance liquid chromatography (HPLC), trace
      amounts of five impurities were detected and the total amount was estimated to be
      less than 1.4%; assay by HPLC, 99.9%. Based on the above results, the raw
      material was authorized as the Japanese Pharmacopoeia Standard (Control 991).

PMID- 11534118
TI  - [Prednisolone Sodium Phosphate Reference Standard (Control 001) of National
      Institute of Health Sciences].
AB  - The raw material for prednisolone sodium phosphate was examined for the
      preparation of the "Prednisolone Sodium Phosphate Reference Standard (Control
      001)". The analytical data obtained were: pH, 7.9; optical rotation, [alpha]D20 =
      +98.0 degrees; UV spectrum, lambda max of 248 nm and specific absorbance in
      ethanol at 248 nm = 306.7; IR spectrum, same as that of the Prednisolone Sodium
      Phosphate Reference Standard (Control 892); thin-layer chromatography, five
      impurities were detected at 200 micrograms; high-performance liquid
      chromatography (HPLC), total amount of impurities estimated to be less than 3.7%;
      residual solvent, 0.0% (ethanol) and 0.0% (hexane); loss on drying, 2.7%. Based
      on the above results, the raw material was authorized as the Prednisolone Sodium
      Phosphate Reference Standard (Control 001) of the National Institute of Health
      Sciences.

PMID- 11534119
TI  - [Estradiol Reference Standard (Control 001) of National Institute of Health
      Sciences].
AB  - The raw material of tocopherol was tested for the preparation of "Estradiol
      Reference Standard (Control 991)". Analytical data obtained were: melting point,
      178.5 degrees C: UV spectrum, lambda max of 281 nm and specific absorbance in
      ethanol at lambda max = 77.7; IR spectrum, same as that of the Estradiol
      Reference Standard (Control 964); optical rotation, [alpha]D20 = +79.5 degrees;
      thin-layer chromatography, one impurity was detected; high-performance liquid
      chromatography (HPLC), total amount of impurities estimated to be less than 0.6%;
      loss on drying, 3.3%; assay, 100.2% by UV spectrophotometry and 99.9% by HPLC.
      Based on the above results, the raw material was authorized as the Estradiol
      Reference Standard (Control 001) of the National Institute of Health Sciences.

PMID- 11534120
TI  - [Heparin Sodium Reference Standard (Control 991) of National Institute of Health
      Sciences].
AB  - The National Institute of Health Sciences Reference Standard for Heparin Sodium
      (Control 991) was prepared. The potency of heparin sodium for the candidate
      reference standard was assayed against "Heparin Sodium Reference Standard
      (Control 871)" by JP Method in collaboration with 4 laboratories, and estimated
      as 1,453 +/- 25 units per ampoule. The filling amounts of heparin sodium in
      ampoule was estimated as 7.46 +/- 0.15 mg per ampoule, and the precision of
      filling into ampoule was about 2.0% as C.V. Based on the above results, the
      candidate was defined as 1450 units per ampoule, and was authorized as the
      Heparin Sodium Reference Standard (Control 991) of the National Institute of
      Health Sciences.

PMID- 11534121
TI  - [The Endotoxin 10,000 Reference Standard of the National Institute of Health
      Sciences (the Japanese Pharmacopoeia Endotoxin 10,000 Reference Standard)
      (Control 0001)].
AB  - To establish the fourth lot (Control 0001) of the Endotoxin 10,000 Reference
      Standard of the National Institute of Health Sciences (the Japanese Pharmacopoeia
      Endotoxin 10,000 Reference Standard), a candidate standard (CS) was prepared and
      then evaluated. The potency of the CS was assayed against USP Endotoxin Reference
      Standard (Lot G-1) and defined as containing approximately 20,000 endotoxin units
      (EU) per vial by a collaborative study in which 5 laboratories participated.
      Based on the results, the CS was authorized to be the fourth lot of the Endotoxin
      10,000 Reference Standard containing 20,000 EU per vial.

PMID- 11534123
TI  - [The relationship between three dimensional structure and functional activity
      observed in the chemical compounds on biological system].

PMID- 11534122
TI  - [Studies on establishment of rapid and sensitive toxicologic biomarkers in risk
      assessment].

PMID- 11534124
TI  - [Nitric oxide (NO) donor].
AB  - Nitric oxide (NO), which is synthesized from L-arginine by nitric oxide synthase
      (NOS) in mammals, acts as a signal molecule for vasorelaxation, cytotoxicity and
      neurotransmission. The difficulty in handling of a gaseous and labile NO causes
      problems with the effective and precise studies using NO. The increasing interest
      in the biological roles of NO requires the use of NO donors which releases NO
      under the various desirable conditions. We systematized the most commonly used NO
      donors in this article to support the biological investigation. NO donors were
      classified according to the functional groups based on NO-donating
      characteristics. The preparation, chemical properties and NO-donating ability of
      these NO donors are summarized. It is particularly described in some detail on
      the stability both as a solid and in solution and the handling of the compounds.

PMID- 11534125
TI  - [Studies on poisonings and incidents caused by chemicals in Japan].
AB  - The criminal cases of poisonings caused by poisonous, deleterious or other
      hazardous chemicals in Japan were studied. The data (111 cases) were collected
      mainly from the newspaper database (Aug. 1984-Feb. 1999). More than half cases
      were caused by chemicals which are regulated by the "Poisonous and Deleterious
      Substance Control Law". Copy-cat poisonings occurred in succession in 1984-1985
      and 1998. Many cases occurred at the laboratories of institutes and universities,
      and hospitals where there are various kinds of chemical reagents. The cases of
      chemical incidents such as those which occurred while transportation were also
      discussed.

PMID- 11534126
TI  - [Teratogenicity study of 2,2,3,3,3-pentafluoro-1-propanol (5FP) in rats by oral
      administration].
AB  - Teratogenicity of 2,2,3,3,3-pentafluoro-1-propanol (5FP), an alternative cleaning
      agent for chlorofluorocarbon, was examined in rats. 5FP was diluted with sesame
      oil and given to pregnant rats (Crj: Wistar) by gavage once a day from day 7 to
      17 of pregnancy at doses of 0, 250, 500 and 1000 mg/kg/day. The pregnant rats
      were sacrificed on day 20 of pregnancy and their fetuses were examined for
      malformation. In the pregnant rats, 5FP caused wheezing, salivation, ptosis,
      reduced body weight gain and reduced food consumption at 500 and 1000 mg/kg/day.
      In the fetuses, 5FP reduced body weight, increased the incidences of skeletal
      variations and retarded the ossification at 1000 mg/kg/day, but did not increase
      the incidences of malformations. It was concluded from these results that 5FP has
      no teratogenicity in rats when given by gavage. The no-observed-adverse-effect
      level was 500 mg/kg/day for rat fetuses, and 250 mg/kg/day for pregnant rats.

PMID- 11534127
TI  - [Teratogenicity study of morpholine salts of fatty acids (oleic acid, 50% water
      solution) in rats by oral administration].
AB  - Teratogenicity of morpholine salts of fatty acids was examined in Wistar rats
      (Crj: Wistar). Morpholine salts of fatty acids (oleic acid, 50% water solution)
      was given to pregnant rats by gavage once a day from day 6 through day 15 of
      pregnancy at doses of 0, 234, 468 and 936 mg/kg/day. The pregnant rats were
      sacrificed on day 20 of pregnancy and their fetuses were examined for
      malformation. Morpholine salts of fatty acids caused nasal discharge, dirty nose
      and salivation in pregnant rats at doses from 234 mg/kg/day. However, fetal
      effects, such as malformation and growth retardation, were not observed even at
      936 mg/kg. It was concluded that morpholine salts of fatty acids has no
      teratogenicity in rats when given by oral administration. The no-observed-adverse
      effect level was 936 mg/kg/day for rat fetuses and less than 234 mg/kg/day for
      pregnant rats.

PMID- 11534128
TI  - [A 90-day repeated dose toxicity study of madder color in F344 rats: a
      preliminary study for chronic toxicity and carcinogenicity studies].
AB  - A 90-day toxicity study of madder color was performed in F344 rats by feeding the
      pellet diet containing 0, 0.6, 1.2, 2.5 and 5.0% of test substance to clarify its
      toxic potential and to determine the dose levels for the following chronic
      toxicity/carcinogenicity studies. Body weight gain and food consumption were dose
      dependently decreased at 1.2% or more in males and at 2.5% or more in females
      throughout the experimental period. All animals were survived until the end of
      experiment and subjected to autopsy. Hematologically, the following parameters
      were fluctuated in relation to the treatment: decreases in the red blood cells,
      hemoglobin, and hematocrit in females at 2.5% or more; increase of platelets in
      males at 2.5% or more, and in females at 5%; increase in white blood cells in
      males at 5%. Serum protein parameters were also affected by the treatment in
      males at 1.2% or more and in females at all doses. Increase in the serum calcium
      level was observed in males at 2.5% or more and in females at 5%. Serum inorganic
      phosphorus level was also increased in males at 1.2% or more and in females at
      2.5% or more. At autopsy, both absolute and relative kidney weights of females
      increased dose-dependently at 0.6% or more. Relative liver weight in females also
      increased at 1.2% or more. Histopathologically, microvesicular vacuolar
      degeneration of proximal tubules was observed in the kidney of both sexes (males
      at 1.2% or more; females at 0.6% or more). In addition, mononuclear cell
      infiltration (both sexes) and hyaline casts and tubular regeneration (male)
      appeared in the kidney at 5%. In the female liver, focal liver cell necrosis
      associated with mononuclear cell infiltration was evident at 5%. The results
      demonstrate the toxic effects of madder color on the liver (in females at 5%) and
      kidney (in males at 1.2% or more; in females at 0.6% or more) of F344 rats when
      treated orally for 90 days. In addition, toxicities in hematopoietic system
      and/or bone would probably be appeared when rats are treated with 1.2% or more of
      madder color for long-term over 90 days. NOAEL was determined to be 0.6% in
      males, but could not be determined in females under the condition of this study.
      Based on the results of this study, the dose levels for subsequent chronic
      toxicity and carcinogenicity studies were determined to be 0.2, 1.0 and 5.0%, and
      2.5 and 5.0%, respectively.

PMID- 11534129
TI  - [A 90-day repeated dose oral toxicity study of magnesium chloride in F344 rats].
AB  - In order to examine the toxicity of magnesium chloride hexahydrate, four groups
      of 10 male and 10 female F344 rats received the compound by dietary
      supplementation at 2.5, 0.5, 0.1 or 0% for 90 days. No treatment-related death
      was observed during the study. Transient soft stool and sustained increase in
      water consumption were observed both in males and females of the 2.5% group and
      slight reduction in body weight gain was noted in the high-dose males. There were
      no toxic changes in food consumption, organ weights, hematology and biochemistry,
      and histopathological examinations in any treated-groups. Based on these results,
      the no-observed-adverse-effect-level was estimated to be 0.5%, and 2.5% is
      considered to be appropriate as highest dose for a 2-year carcinogenicity study.

PMID- 11534130
TI  - [Study on the characterizations of genus Curcuma plants on the strains of C.
      longa L. and C. aromatica Salisb preserved at Izu station of NIHS].
AB  - To clarify the characteristics of genus Curcuma plants, we studied the properties
      of six strains of Curcuma longa L. and two strains of C. aromatica Salisb.
      preserved at Izu Experimental Station for Medicinal Plants of National Institute
      of Health Sciences. Six strains of C. longa were classified into three types
      according to morphological characteristics, rhizome production, and differences
      in curcuminoid content of rhizome. The curcuminoid content of the rhizomes in
      each strain ranged from 2.20 mg/g to 55.23 mg/g. Strains showing a high
      curcuminoid content had a low rhizome yield. No difference was observed between
      two strains of C. aromatica in terms of morphological characteristics. C. longa
      can be easily distinguished by differences in the development of tuberous roots
      and the color of the rhizome cross section.

PMID- 11534132
TI  - [Development of domain specific search engines].
AB  - As cyber space exploding in a pace that nobody has ever imagined, it becomes very
      important to search cyber space efficiently and effectively. One solution to this
      problem is search engines. Already a lot of commercial search engines have been
      put on the market. However these search engines respond with such cumbersome
      results that domain specific experts can not tolerate. Using a dedicate hardware
      and a commercial software called OpenText, we have tried to develop several
      domain specific search engines. These engines are for our institute's Web
      contents, drugs, chemical safety, endocrine disruptors, and emergent response for
      chemical hazard. These engines have been on our Web site for testing.

PMID- 11534131
TI  - [Characteristics of Papaver somniferum L. cv. ikkanshu cultivated in Izu].
AB  - The seeds of Papaver somniferum L. cv. Ikkanshu were sown in November (Autumn
      sowing: AS) and March (Spring sowing: SS) in a field at Izu Experimental Station
      for Medicinal Plants of National Institute of Health Sciencs, and both AS and SS
      plants were cultivated to investigate their growth, opium yield and alkaloid
      content in the opium. Growing periods from the sowing to the opium harvest were
      approximately six months for AS plants and three months for SS plants. Sizes of
      plants and capsules in AS were bigger than those in SS, reflecting their growth
      period. Opium yields per an are in AS and SS were 212.09 g and 142.03 g,
      respectively. The opium was able to be collected four times in the AS plants
      though the SS plants ceased to exude opium after the second incision. Therefore
      higher yield of opium in AS plants seems to be attributed to an amount of opium
      in the third and fourth incision. Average morphine content in the total opium was
      15.61% in AS plants and 15.04% in SS plants, and the estimated amounts of
      morphine per an are in AS and SS plants were 33.16 g and 21.38 g, respectively.

PMID- 11534133
TI  - [Archives of environmental health digital maps and their delivery by the
      Internet].
AB  - Geographic Information System is becoming a very important tool for environmental
      health research. We have produced various digital maps for different scales for
      different purposes. The burst of E. Coli O-157, distribution of hazadarous
      chemicals in East Asia, and coastal resin pellets are some examples. It now
      becomes a problem how to archive these digital maps and how to retrieve these
      maps according to user's request. We have developed a computer system that can
      store various types of digital maps and can retrieve them from WWW client
      machines. The key concept of this archive system is to classify every digital
      maps according to their region of interest.

PMID- 11534134
TI  - [Distribution and origin of plastic resin pellets as environmental pollutants at
      the East China Sea area].
AB  - Plastic debris are important marine pollutants. Plastic debris consist of resin
      pellets and waste plastics. We are particularly interested in resin pellets. We
      made field survey of resin pellets at nearly 400 sites in 200 beaches in Japan
      and neighboring countries. The pellets were found at all most all Japan coasts we
      surveyed and at some beaches of Macao, Hong Kong, Xiamen, the north of Taipei,
      and Cheju Island in Korea. The number of pellets was more than 1000 pieces per m2
      on the most abundant beach in Japan. Through further analysis using GC/ECD,
      endocrine disrupting chemicals, PCBs, DDTs, HCHs and Nonylphenol were detected in
      selected samples. Biota such as Bryozoa were observed on the surface of pellets
      washed up on the beaches in subtropical areas. Pellets has been suspected to
      affect wildlife and human health, but we have no report on affection to human.

PMID- 11534135
TI  - [Spatial organization of the thalamic projections in the dog striatum].
AB  - Using the method based on retrograde transport of markers injected into different
      segments of caudate and accumbent nuclei and putamen peculiarities of labelled
      neurons distribution in thalamic nuclei of the dog brain were studied. Zones of
      projection of motor and limbic thalamic nuclei and overlapping of terminal fields
      of fibres projection neurons of thalamic nuclei that function in different
      systems were demonstrated in the striatum. Comparative analysis of
      thalamostriatal projections organization in dogs, cats and monkeys allowed to
      reveal certain diversities in their construction as well as similarities.

PMID- 11534136
TI  - [Macrophages in the choroid plexus of the embryonic telencephalon].
AB  - Using electron microscopy and immunocytochemistry distribution of macrophages in
      anlage of telencephalon choroid plexus was studied in 5-9 wks old human embryos.
      CD68 gene expression by intraepithelial macrophages that appear in anlage of
      choroid plexus (epithelial plate) was established to begin at 5th week of
      development. Accumulation of macrophages in embryonic connective tissue of
      choroid plexus anlage, appearance of intraepithelial macrophages, following
      appearance of free macrophages and supraependymal cells in brain ventricles (on
      wk 6-7) indicates that in human embryos choroid plexus anlage is a migration zone
      for macrophageal serie cells that penetrate into the cavity of the developing
      brain.

PMID- 11534137
TI  - [Innervation centers in the cervical and thoracic trachea].
AB  - Using HRP axonal transport links between trachea and ganglia of cervical thoracic
      regions of right and left sympathetic trunks, spinal ganglia and vagal posterior
      ganglia were established. Quantitative and morphometric characteristics of
      neurocytes of contralateral ganglia involved into trachea innervation were given.
      Peculiarities of localization of innervation centres of cervical and thoracic
      trachea regions were established.

PMID- 11534138
TI  - [Tensile strength properties of lower limb nerves in the mature age].
AB  - Tensile strength and deformation properties of tibeal and common fibular nerves
      were analysed in 78 cadavers of both sexes people aged from 21 to 60. It was
      established that in mature age nerve tensile strength and elasticity increases
      with low extent of elongation. At the age from 21 to 50 tensile strength and
      rigidity decrease with significant deformations due to nerve fibre degeneration.
      After 50 ys tensile strength and rigidity grow higher due to the developing
      sclerosis of nerve trunks. The nerves studied posses equal tensile strength that
      decreases synchronously during the period of maturity. Changes of deformation and
      tensile strength properties of the nerves within the period of maturity is
      connected with age-related reorganization of their intratruncal structure.
      Diversities in mechanical properties of different nerves is determined by
      qualitative and quantitative peculiarities of their morphological structure.

PMID- 11534139
TI  - [Adaptive reaction of the dog right cardiac ventricle in dosed hypokinesia].
AB  - Complex morphological study of the heart was carried out experimentally in 48
      adult outbred dogs exposed to dosed hypokinezia. 5 periods of the organism
      adaptation to hypokinezia were distinguished, within which significant
      correlations between different organometric parameters were demonstrated.
      Individual variations of adaptive reactions of the heart ventricles to the new
      haemodynamic situation were established.

PMID- 11534140
TI  - [Compensatory responses in lymph nodes following by prenatal indomethacin
      exposure].
AB  - Retardation of development of the structures of mesenteric lymph nodes (maximum
      at first 1-2 wks) was discovered in rats treated with indometacin. It was
      dependent on the doze of preparations. Mast cells and eosinophilic reactions
      associated with normalization of the stroma structure and functional activity of
      lymph nodes nerve structures took place in the lymph node substance as adaptive
      processes on the background of lymphocytopenia and incomplete development of the
      lymph node B zone by weeks 2-3.

PMID- 11534141
TI  - [Characteristics of lymphocyte recirculation through postcapillary venules of
      lymph node paracortical zone following antigenic stimulation].
AB  - The walls of venules of paracortical zone of popliteal lymph nodes were studied
      in 127 2-5 Ys old male dogs (15-20 kg of body weight) after subcutaneous
      injection of BCG vaccine 0.2 mg/kg in dose. 6 hrs after the administration of BCG
      vaccine the venule diameter was found to reduce. Then it gradually increased and
      returned to initial parameters after 3 months. Lymphocyte number was increased in
      venular lumen and walls following antigenic treatment. Microvilli number growth
      was observed in endotheliocytes. Basement membrane in the venules was loosened.
      Lymphocytes through endotheliocytes. Maximal lymphocyte activity and
      modifications of venular walls was observed on d 7 following the BCG vaccine
      administration.

PMID- 11534143
TI  - [Mesenteric lymph nodes in rats exposed to emotional stress].
AB  - Structural and functional peculiarities of mesenteric lymph nodes were studied in
      40 stressed August rats using micro anatomical methods. The stress was induced by
      limitation of any movement for 5 hrs every day. Peculiarities and intensity of
      modifications demonstrated was dependent on duration of stress actions.
      Significant decrease of cortical substance area, its lymphoid nodules length and
      width and germinal centre area, fraction of large, medium and small lymphocytes
      was observed following 5 hrs of the experiment, which was combined with expansion
      of the area, occupied by medullar substance. On the 2nd d of 5 hrs experiment
      cortical substance area was widened (on histological section), the number and
      sizes of lymphoid nodules grew up and lymphoid nodules appeared in medullar
      bands. On the 3rd experimental day mesenteric lymph node structure gradually
      restored. It showed control values on the 6th experimental day.

PMID- 11534142
TI  - [Mesenteric lymph nodes of newborn from mothers with kidney diseases].
AB  - Microtopography and cellular content of mesenteric lymph nodes were studied in
      children who were born from healthy mothers (group 1) and from mothers with
      nephropathy (group II) and chronic pyelonephritis (group III). Lymph nodes of
      newborns from mothers with chronic pyelonephritis develop much slower than in
      control children and that from mothers with nephropathy. Lymph nodes in group II
      children resemble those of control group in their structure but its cellular
      content does not correspond control values. Morphological immaturity of lymph
      nodes of children from mothers with pyelonephritis allows to relate them to risk
      group that acquire significant immunomodulating correction.

PMID- 11534144
TI  - [Lymphoid structures and their cellular content in the cecum in 1-3 years old
      children (early childhood)].
AB  - In 1-3 Ys old children (early childhood) coecal lymphoid nodules are well
      developed with lymphatic capillaries and high endothelium venules in their base.
      The highest concentration of lymphoid cells is also noted there. In the apical
      zone, central part and nodule base cellular content has certain features. Lamina
      propria of the coecal mucosa contains great number of plasmic cells.

PMID- 11534145
TI  - [Bronchial parameters in inhabitants from the North].
AB  - The number of branches in the bronchial tree as a whole and in each generation
      was calculated on corrosion preparations of the right lung in 16 male inhabitants
      of Novosibirsk and Magadan. Diameters and lengths of a trachea, main, lobar,
      segmentary and subsegmentary bronchi, interlobular, lobular and terminal
      bronchioles were determined. The parameters of the 9 first generations were
      measured completely while those of distal airways--by 15% occasional choice. In
      both groups the number of branches in the generation was established to grow
      proportionally to generation number growth and then to decrease due to asymmetry
      of branches and termination of the part of them at the level of terminal
      bronchiole. In Magadan inhabitants bronchial tree was longer and wider. The
      anatomical dead space was 1.6 fold larger in North inhabitants than in that of
      Novosibirsk. Comparison to physiological data shows that in Novosibirsk
      inhabitants anatomic dead space makes 27% of respiratory volume, while in that of
      Magadan--34%. As a result the volume of the air inhaled in North inhabitants
      which is blended in airways is greater than in Western Siberia people.

PMID- 11534146
TI  - [Morphometric study of the human right and left kidney glomeruli--age factors].
AB  - 80 autopsy kidneys were studied in healthy people of both sexes. All of them had
      only one artery. The material was distributed into 4 age groups: first period of
      maturity (21-35 Ys old women, 22-35 Ys old men), second period of maturity (36-55
      Ys old women, 36-60 Ys old men), pre-senile (56-74 Ys old women, 61-74 Ys old
      men) and senile (75-90 Ys old people) age. Statistically significant difference
      was not determined in none of age groups during comparison of the results of
      morphometric study of right and left kidney glomeruli.

PMID- 11534147
TI  - [Ultrastructural characteristics of reactive changes in the epithelium of the
      kidney proximal tubules in massive proteinuria in children].
AB  - The investigation was designed to analyse the mechanism of the protein transport
      on the basis of the estimation of ultrastructural organization of the epithelium
      of proximal convoluted tubules of kidneys of the children, suffering from the
      nephritic form of glomerulonephritis for a long time. It was established that
      high tubular proteinuria (from 0.33 to 6.6 g/l) causes many changes in apical,
      central and basal parts of epithelial cells as well as in intercellular spaces.
      It was stated that massive proteinuria provoked adaptive processes in epithelial
      cells of proximal tubules. At the same time signs of exhaustion of adaptive
      capacities of proximal nephrocytes were demonstrated.

PMID- 11534149
TI  - [Tasks of the Journal in the year 2001].

PMID- 11534148
TI  - [Proliferation and differentiation of regenerating Leydig cells following
      ethylene dimethane sulfonate exposure in rats].
AB  - Cell type of mammalian testis which is involved in the synthesis and secretion of
      testosterone and the maintenance of spermatogenesis are the fully differentiated
      interstitial Leydig cells (LC). Their ultrastructure possesses the typical
      characteristics of steroid-producing cells. It has been generally accepted that
      two waves of proliferation and differentiation can be discerned during the
      development of the Leydig cell population in the rodent and human testis.
      Treatment with ethane dimethane sulphonate (EDS) destroys selectively LC. A new
      LC population develops in the following weeks and this model has been used by us
      to study the proliferation and differentiation of new LC. Our results support the
      suggestion that the regeneration of a new LC population following EDS
      administration shows many similarities with the formation of the adult type LC in
      the prepubertal mammalian testis.

PMID- 11534150
TI  - [Constitutional characteristics of X-ray anatomical parameters of the diaphragm].
AB  - The front straight projections roengenograms and fluorograms of the chest of 1379
      healthy persons of both sex, aged 17-22 were studied. Their somatic type was
      defined beforehand on the gabarital variation level. It was determined that the
      basic diaphragm roentgeno-anatomical characteristics (the height and form of its
      dome, the distance from the highest point of the right diaphragmatic dome to the
      right clavicle shadow-the chest height) have pronounced typical features. The
      interdependency between the diaphragmatic domes form and the cardiovascular
      position was detected.

PMID- 11534151
TI  - [Effect of a method of cytological smear fixation on characteristics of
      epitheliocytes of mouth mucosa].

PMID- 11534152
TI  - [Cellular level of the body adaptation to the environmental exposure in the large
      industrial city (Saint-Petersburg)].
AB  - By methods of light and electron microscopy structural disturbances of heart,
      kidneys, liver and pancreas were studied in rats pups who were born and kept for
      a year at kindergartens of city districts diverse in level of environmental
      pollution (air and soil). The content of micronuclei in epitheliocytes of oral
      mucosa in 5-6 ys old children from the kindergartens was controlled in order to
      detect chromosome aberrations. The examination of morphofunctional state of the
      organs studied and cells containing micronuclei carried out in different
      districts of the city allowed to reveal correlation between disorders studied and
      the level of environmental pollution.

PMID- 11534153
TI  - [Functional morphology of human ovulation].

PMID- 11534154
TI  - [V Congress of the International Association of Morphologists].

PMID- 11534155
TI  - [University of Luvenne and Andreas Vesalius].

PMID- 11534156
TI  - [On the way to the discovery of the bone marrow stem cells].

PMID- 11534157
TI  - [Evaluation of caries susceptibility in Northern Russian population by evaluation
      of medium-weight-molecular substances and oligopeptides].
AB  - Students of the Arkhangelsk State Medical Academy living in this area from the
      birth date and those from other climatic zones were examined. The metabolic
      status indices were defined content of low and middle molecular mass substances
      in blood and mixed saliva. There were certain features of biological fluidin
      spectrograms of caries susceptible persons. It was found that caries
      susceptibility of teeth depends on middle molecular substances pool in biological
      fluids.

PMID- 11534158
TI  - [Chemical anabiosis by aldehydes and protection of organs and tissues from
      ischemic damage].
AB  - The article is devoted to the medical biological problem that is the impact of
      endogenic aldehyde (methylenglucol) on tissue structures with the purpose of
      defending them from ischemic damage by reverse reduction of intensity of
      metabolic reactions, which is conditioned by reverse inhibition of the oxidation
      processes phosphorylation connected with reduction of losses and adenosine 5
      triphosphate forming. It is ascertained that until methylenglucol in the ischemic
      tissue of concrete organ hasn't reduced to a certain critical level there is
      still an opportunity to reanimate this organ.

PMID- 11534159
TI  - [Comparative evaluation of various materials used for hermetic sealing of the
      root channel opening after obturation].
AB  - The quality of hermetic sealing of the opening of an obturated root channel with
      various sealing materials (Bezline and Russian material Foscin and Belokor) was
      studied. Root channels were obturated using Endomethason, Forfenan, and gutta
      percha pins with hermetic AN-PLUS. A total of 187 teeth of different groups were
      filled in patients aged 17-85 years. The quality of hermetic sealing of an
      obturated root channel was evaluated by x-ray examination and electrometrically
      directly after filling (in 10 min) and in remote periods (after 6, 12, and 24
      months). The best results were attained with Bezline and gutta-percha. A
      combination of Bezline and Endomethason yielded satisfactory results.

PMID- 11534160
TI  - [The problem of dysbiosis in practical dentistry].

PMID- 11534161
TI  - [Clinical, topographic, and morphological characteristics of pathological
      processes in the retromolar zone].
AB  - Morphological variants of 20 tissue fragments of mandibular retromolar space were
      analyzed and the data were used for developing a protocol of treatment of
      difficult eruption of the mandibular third molar using biocomposite materials.

PMID- 11534162
TI  - [A classification of mandibular fractions].
AB  - A new classification of mandibular fractures is suggested. Unlike fractures of
      the upper and middle zones of the face, mandibular injuries are characterized by
      typical location and configuration, which prompted us to undertake this study.
      Literal and digital symbols were used in formulation of the diagnosis. These
      symbols characterize the line of fracture, involved teeth, site of fracture,
      presence (or absence) of dislocated fragments, occlusive disorders, combined
      injuries, status of soft tissues at the site of injury, presence of inflammation
      in the fracture fissure and its severity. Examples demonstrating the convenience
      of the formula are presented.

PMID- 11534163
TI  - [Prevention of inflammatory complications after mandibular osteosynthesis by a
      combination of low-frequency ultrasound and laser exposure].
AB  - Clinical and laboratory study of the efficiency of separate and combined use of
      low-frequency ultrasound and laser exposure of the operative wound for prevention
      of pyoinflammatory complications during mandibular osteosynthesis was carried
      out. Clinical parameters of wound reparation in the course of healing and
      microbiological and cytological findings in various methods of treatment are
      presented. The results evidence a high efficiency of these physical methods,
      particularly of their combination.

PMID- 11534164
TI  - [Adaptation and compensatory reactions in dentition defects as shown by
      masticatory test with ascending loading].
AB  - Adaptation and compensatory reactions developing during deterioration of
      dentition status were evaluated using masticatory test with dynamic loading,
      developed by the authors. The study was carried out in subjects with intact
      dentition, with partial defects, with bridge and complete removable dentures.

PMID- 11534165
TI  - [Training and upgrading of dentists].

PMID- 11534167
TI  - [Delayed expert evaluation of the quality of orthodontic treatment in civil
      actions].

PMID- 11534166
TI  - [Comparative analysis of results of mathematical simulation of stressed deformed
      status of pin dentures of different design].
AB  - A computer study of 99 types of mathematical models of teeth armed with stump pin
      insertions widely used in dentistry (group 1--anchor pins and group 2--cast pin
      insertions suggested by the authors). Tooth models differed by shape, size, and
      properties of the design material. The shape and parameters of stump pin
      insertion were proven to be more significant than the properties of design
      material. The choice of pin design is determined by the clinical situation,
      topography and anatomy of tooth crown destruction, and maxillodental disease.

PMID- 11534168
TI  - [Diagnosis and choice of treatment strategy in children with chronic pulpitis of
      deciduous teeth].

PMID- 11534169
TI  - [Organization of care for patients with oral mucosal and labial precancer
      diseases].

PMID- 11534170
TI  - [Characteristics of dental caries in Azerbaijan].

PMID- 11534171
TI  - [Medical ozone in dentistry].

PMID- 11534172
TI  - [Modern aspects of studying phytohormones. Cytokinins].
AB  - The review presents current data on mechanisms of cytokinin action in plants. By
      analogy with the first part (Ivanova et al., 1999), in which general principles
      of phytohormone action and cardinal trends of phytohormone investigations were
      examined, here the relevant information on mechanisms of action of auxins and
      gibberellins has been given, and taking cytokines as example an attempt has been
      done to summarize the literature data on the number of questions offered for
      analysing hormones of high animals (Gudwin, Merser, 1986). The review
      demonstrates that mechanisms of cytokine action at the cellular level are not
      known in many cases. One of the most significant factors in the action of
      phytohormones of this class on plants is their concentration, determined by their
      synthesis, transportation and further chemical conversions. This paper points to
      a poor knowledge of the relative role of these processes in regulation of
      cytokinin contents and their distribution among plant organs. Two possible ways
      of studying cytokinin action at the present day stage of investigations have been
      designated: 1) revealing the cytokinin expressed genes and establishing
      mechanisms of their action; 2) estimation of endogenous cytokinin alteration and
      the influence of this alteration on definite processes in the cell with the help
      of ipt-gene from t-DNA of Agrobacterium tumefaciens.

PMID- 11534173
TI  - [Morphofunctional parameters of the nucleoli during development of polyploid
      nutrient cells of gonads from the snail Succinea lauta].
AB  - Ag-protein contents, integral area and number of nucleoli in polyploidizing
      nuclei of gonadal nutrient cells of the snail Succinea lauta were estimated on
      the squashed preparations by means of morphometry and cytophotometry. 8 NORs of
      different size were found in haploid chromosome set of prophase spermatocytes (n
      = 22), but usually 1-2 nucleoli per 2c DNA are present in the nutrient cell
      nuclei. During genome multiplication from 2c to 32c-64c the Ag-proteins content
      of nucleoli increased proportionally to gene dosage, but irregularly: before 8c
      level the coefficient of increasing in each endocycle was more than 2; from 8c to
      16c it was 2; after 16c-level it usually decreased to 1.6-1.3. This dynamics
      reflects the effects of several factors on nucleolar activity: endomitotic
      polyploidy (gene dosage effect), differentiation and rhythmic functioning of
      tissue. Increasing indexes of integral area and the number of nucleoli during
      polyploidization were significantly less, than increasing index of Ag-proteins.
      The lag of nucleolar area for 4 cycles (2c-32c) was 32%, and number of nucleoli
      per diploid set decreased from 2 to 1. It may be due to NOR aggregation
      corresponding chromosomes. The photometric index of Ag-protein content more
      adequately reflects in the nucleolar activity during development and functioning
      of tissues.

PMID- 11534174
TI  - [Evolutionary regularities of the appearance of polyploidy in salivary glands of
      gastropod mollusks. III. A subclass of Pectinibranchia: Orders Discopoda,
      Echinospirida, Aspidophora and Entomostoma (Mesogastropoda)].
AB  - By means of histological methods and DNA cytophotometry, a study was made of the
      salivary glands of 16 species of gastropod molluscs belonging to the subclass
      Pectinibranchia and making a group of Mesogastropoda. Four cell types of salivary
      glands were distinguished: granular cells (with glycoproteid granular
      inclusions), mucocytes-I (with sulfatic acid mucopolysaccharides), mucocytes-II
      (with neutral and acid polysaccharides and proteins), and also the epithelial
      ciliated cells and mucous duct cells. Data of experiments on starvation and
      synchronous feeding of molluscs have testified that all described cell types are
      independent. In some species differentiation on protein and mucous departments
      within the glandular epithelium was shown. In some marine representatives of the
      orders Discopoda and Aspidophora polyploid cells with the ploidy levels from 8c
      to 32c were revealed along with diploid cells. The ecological and phylogenetic
      regularities of somatic polyploidy manifestation in Mesogastropoda are discussed.

PMID- 11534175
TI  - [Structural-functional changes in root cells under the action of carbonylcyanide
      3-chlorphenylhydrazone].
AB  - Structural and functional changes in wheat root cells under the action of
      protonophores-carbonyl cyanide m-chlorophenylhydrazone (CCCP) were studied. After
      addition of 0.5 mM CCCP we observed K+ ions uptake from the incubation medium,
      stimulation of O2 uptake which correlated with the occurrence of condensed
      mitochondria in the cells (1, 4, 6 h of incubation), and an insignificant
      increase of heat in roots. Taking into account the protonophoric properties of
      CCCP, we assume what the observed changes may be associated with the activation
      of a reverse energy dependent transport of H+ ions from the cytoplasm, due
      partially to H(+)-ATPase function intensification. The addition of
      diethylstibestrol (DES), a specific inhibitor of plasma membrane H(+)-ATPase,
      completely eliminated the stimulating effect of CCCP, that confirms the earlier
      assumption.

PMID- 11534176
TI  - [Hepatocytes in heterokaryons can suppress entry into the S-period of fibroblast
      nuclei from murine NIH 3T3 cells].
AB  - Mouse liver regeneration after partial hepatectomy can be considered as a
      spectacular example of controlled tissue increase. In this study serum-deprived
      (0.2%) resting and serum-stimulated (10%) proliferating NIH 3T3 mouse fibroblasts
      were fused with primary hepatocytes isolated from normal (intact) and
      regenerating adult mouse liver at different times after partial hepatectomy (1-15
      days) to elucidate mechanisms of liver cell proliferation cessation at the
      regeneration end. DNA synthesis was investigated in the nuclei of heterokaryons
      and non-fused cells using radioautography. Hepatocytes isolated from regenerating
      liver within 1-12 days following operation did not retard the entry of stimulated
      fibroblast nuclei into the S-period. In contrast, hepatocytes isolated within 15
      days after hepatectomy were found to have inhibitory effect on the entry of
      stimulated fibroblast nuclei into the S-period in heterokaryons. Preincubation of
      these hepatocytes with cyclocheximide for 2-4 h abolished their ability to
      suppress DNA synthesis in stimulated fibroblast nuclei in heterokaryons. Possible
      reasons of inhibitory effect of differentiated cells in heterokaryos are
      discussed. The data obtained enable us to conclude that the mechanism of
      proliferative process control in regenerating hepatocytes seems to be stopped
      being affected by the intracellular growth inhibitors, whose formation depends on
      protein synthesis.

PMID- 11534177
TI  - [Intracellular localization of calcium in loach embryonic cells at the early
      gastrula stage].
AB  - Intracellular localization of calcium-accumulated structures in the loach embryo
      cells at the state of early gastrulation was determined by electron microscope
      histochemical pyroantimonate method. Calcium-precipitate was observed in the
      nucleus (external and inner membranes, chromatin and nucleolus), and in the
      cytoplasm (ER, mitochondria and submembrane cortical layer). Our present data
      show that such cell organelles as nuclear envelope, ER, and mitochondria serve as
      the basic cellular stores for calcium, confirming the existence of calcium signal
      system both in the nucleus and in the cytosol.

PMID- 11534178
TI  - [Role of parathyroid hormone in regulating the functional activity of platelets].
AB  - We studied the influence of parathyroid hormone (PTH) on the functional activity
      of white rat and human platelets, and examined in particular possible mechanisms
      of PTH influence on the platelet aggregation activity. It has been stated that
      PTH renders a marked dose-dependent proaggregative effect on platelets. Possible
      mechanisms of proaggregative effect of parathyroid hormone were examined on
      platelets using substances with defined mechanisms of the effect. Examination of
      PTH effect on lectin-intermediated aggregation in a suspension of washed
      platelets shows that metabolic activation of platelets by PTH causes an increased
      expression on their plasmic membrane mainly of glycoprotein complex IIb-IIIa and
      in a lesser degree of glycoprotein complexes Ia-IIa and IV which take part in the
      formation of interplatelet contact.

PMID- 11534179
TI  - [Specific regulated endonuclease activity of small RNP, containing prosomes from
      the A431 cell line: possible mechanisms of regulating the stability of RNA by
      epidermal growth factor].
AB  - A comparative study was made of reactive oxygen species (ROS) in rat embryo
      fibroblasts and their transformants. Primary rat embryo fibroblasts (REF), REF
      transformed by the complementing oncogenes E1A plus cHa-ras (cell line E1A +
      Ras), and REF transformed by E1A plus E1B-19 kDa (cell line E1A + E1B) were
      studied. ROS generation was measured with microfluorometric assay using
      fluorescent probe 2',7'-dichlorofluorescin diacetate. It has been shown that the
      block of REF and E1A + 1B cells in the G1/S under serum-starved conditions (0.5%
      serum) for 24-48 h was paralleled by a decrease in ROS generation. Activation of
      serum-starved REF and E1A + 1B cells with 10% serum resulted in reactivation of
      cell cycle and gradual increase in ROS generation. The maximum intracellular
      level of ROS correlated in time with the phase of DNA synthesis. Serum-starved
      E1A + Ras cells were not stopped in the G1/S and ROS production of these cells
      was not dependent on serum growth factors. The prolonged cultivation of E1A + Ras
      cells in the medium with low serum content (0.5%) caused a sharp increase in ROS
      generation, which was accompanied by apoptotic death.

PMID- 11534180
TI  - [Cell cycle and formation of active form of oxygen in rodent fibroblasts].
AB  - Changes in the levels of mRNAs encoding ion transporters (ATP1B1, NHE1, NKCC1),
      beta-actin, GAPDH, regulators of proliferation and apoptosis (p53, Bcl-2) and
      kinase hSGK, involved in cell water regulation, were studied using RT PCR in the
      peripheral human lymphocytes activated with phytohemagglutinin for 4-24 h. The
      common, "grouped", effect that was found was an increase in the levels of the
      studied mRNAs after an 8 h activation, sometimes preceded by a delay or slight
      decrease at the initial stage of 0-4 h. Apart from the common features, some
      differences were observed in the time courses and amplitudes of the responses of
      individual mRNAs. The arrangement of the individual mRNA responses in lymphocytes
      from different donors could differ significantly, thus indicating differential
      regulation of the studied mRNAs apart from the "grouped" effect. The data
      obtained confirmed our suggestion that regulation of ion transport at the level
      of mRNA could be involved in the changes of ion balance at the late stage of
      lymphocyte activation.

PMID- 11534182
TI  - [Re-expression of various i-antigens in Dileptus anser after temporary
      transformation of serotype].
AB  - RNP particles containing 20S prosomes (alpha RNP) isolated from human epidermoid
      carcinoma cell line A-431 are shown to posses strong and regulated endonuclease
      activity specific for high-molecular-weight RNA, particularly, specific mRNAs.
      Furthermore, alpha-RNP destabilize the 3'-untranslated regions of c-myc mRNA,
      creating a specific cleavage pattern. Cleavage point within Alu sequence in high
      molecular-weight RNA has been localized by primer-extension method. This RNase
      activity is induced under the action of EGF. alpha-RNP involvement in the
      coordinated control of processing and stability of specific messenger RNA
      molecules is suggested. The endoribonuclease activity of alpha-RNP can represent
      a link between EGF signalling pathway and RNA processing and degradation.

PMID- 11534181
TI  - [Study of "group" expression of mRNA of the ion transporters ATP1B1, NHE1 and
      NKCC1, beta-actin, glycerophosphosphate dehydrogenase, proteins regulating
      proliferation and apoptosis of p53, Bcl-2, IL-2 and hSGK kinase at the
      prereplicative stage of human lymphocyte activation].
AB  - Previously, we found no segregation in F2 obtained from crosses between two
      Dileptus anser clones differing (under the same culture conditions) in their
      serotypes, i.e. in their immobilization antigens (i-antigens); indeed, all the F2
      clones had mixed, i.e. hybrid serotype, being immobilized simultaneously with
      both immune sera developed against either parental clone (Uspenskaya, Yudin,
      2000). Presently, experiments were carried out to see if this unusual phenotype
      would be re-expressed after a temporary switching off. To switch off both
      expressed i-antigens, serotype transformation was induced in the F2 clones by
      shifting the culture temperature from 25 to 17 degrees C. Two weeks later, when
      the clones returned to the initial temperature conditions, each of them was seen
      to re-express both parental i-antigens. This result is discussed with reference
      to the role of i-antigens in regulation of their own expression as has been
      suggested by some authors.

PMID- 11534183
TI  - [Number, activity and thermostability of the electrophoretic forms of acid
      phosphatase in Amoeba proteus, cultured at different temperatures].
AB  - In free-living amoebae (Amoeba proteus, strain B), cultured at 10 and 25 degrees
      C, we compared the number, activity, and thermostability of separate
      electromorphs of Triton-soluble acid phosphatase (AcP) revealed by disc
      electrophoresis in polyacrylamide gel using 2-naphthyl phosphate (pH 4.0) as a
      substrate. No differences in the number of AcP electromorphs and their mobility
      were observed at both these temperatures. The total activity of AcP
      electromorphas per unit of cellular protein and their total thermostability were
      lower in amoebae acclimated to 10 degrees C than to 25 degrees C. The above
      decrease may be a consequence of a simultaneous decrease in the activity and
      thermostability of two tartrate-sensitive electromorphs, both being of lysosomal
      nature. The total activity and thermostability of tartrate-resistant AcP
      electromorphs did not differ in amoebae acclimated to the two above temperatures.
      In amoebae cultured at 10 degrees C the fall of activity and thermostability of
      lysosomal AcP correlates with the decrease in their primary cell thermoresistance
      and phagocytic activity. The obtained results confirm the earlier conclusion
      (Vysotskaya et al., 1994) that lysosomes may be involved in acclimation of
      electrothermal animals to changing environmental temperatures.

PMID- 11534184
TI  - [Ultrastructural characteristics of thyroid medullary carcinoma].
AB  - 17 thyroid medullary carcinomas (TMC) were studied electron microscopically (EM).
      Two cell groups were revealed regardless of their histological structure: EM
      differentiated (with signs of C-cell differentiation) and non-differentiated
      (without these signs). There is no correlation between histological structure of
      the tumor and the degree of its EM differentiation. In patients who lived 5 years
      maximum after the diagnosis there were different histological types but EM the
      tumors had relatively monomorphous structure with domination of non
      differentiated cells (more than 70%), high content of dark cells (50% and more)
      and low content of desmosomes (less than 30%). The prognosis is more favourable
      the higher is content of EM differentiated cells, the better desmosomes are
      developed and the lower is content of dark cells. The scope of surgery and local
      metastases do not influence the prognosis while distant metastases (stage IV)
      deteriorate the prognosis.

PMID- 11534185
TI  - [Immunohistochemical study in differential diagnosis of benign and malignant
      lesions of the thyroid gland].
AB  - The paper is devoted to immunohistochemical (IHC) investigation of various benign
      and malignant proliferating lesions in the thyroid with a special focus on
      borderline lesions--atypical adenomas (AA) and focal adenomatous areas (FAA). All
      papillary carcinomas (PC) and FAA in Hashimoto thyroiditis demonstrated strong
      immunoreactivity for CK-19. More than 50% of PCNA-positive cells were detected in
      most of the investigated carcinomas; in FAA, and in AA PCNA expression was not so
      prominent but higher than in other adenomas and nodular goiters. Strong
      expression of vimentin by follicular epithelium was detected in PC. In FC, AA and
      FAA it was focal from moderate to strong. In other cases immunoreactivity to
      vimentin was weak or absent. Thus, it is worth to form on the basis of
      histological and IHC results the group of thyroid proliferating processes with
      possible malignant transformation. AA and FAA with more than 10% PCNA
      immunoreactive cells and vimentin expression from moderate to strong should be
      included in this group. Further observation of our patients will enable to assess
      malignant potential of this processes. Besides, CK-19 expression is an additional
      criterion for the diagnosis of early PC.

PMID- 11534186
TI  - [Morphological characteristics of the thyroid of adults from St-Petersburg (using
      a sample study data)].
AB  - 138 thyroids from citizens of St-Petersburg born in this city who died suddenly
      were investigated macro-, microscopically and morphometrically. The average
      weight was 23.72 g, being maximal at the age of 20-29 years and minimal in
      persons over 70 years of age. A slight increase of the weight occurred between 40
      and 49 years of age. Nodular lesions were found in 8.7%. Normoplastic type of
      structure was observed in 84.6%. Areas of asynchronous functioning were found in
      all the cases. It is possible to describe age-specific normal condition of the
      thyroid according to morphometric data: aging results in a decrease of the
      follicle diameter, an increase of thyrocyte height and nuclear diameter, a
      decrease of Brown index, growth and thickening of fibrillar structures. There
      were no convincing data in favour of endemia.

PMID- 11534187
TI  - [Modifications of gastric mucosa in diffuse and intestinal cancer].
AB  - The study was made of 29 intestinal type gastric carcinomas, 37 diffuse type
      gastric carcinomas and stomach mucosa (SM). Both carcinomas slightly differed by
      frequency of the fundal glands atrophy. Intestinal type was characterized by a
      higher frequency of antral glands atrophy, intestinal metaplasia, particularly of
      colon type. Intestinal cell differentiation was about the same in both types.
      Hyperplasia of lining and endocrine cells in the fundal part of the mucosa was
      more frequent and neuroendocrine differentiation was more pronounced in diffuse
      stomach carcinoma. It is suggested that environmental impacts including
      helicobacter pylori result in proliferation of the epithelium, intestinal
      metaplasia, dysplasia and carcinoma of the intestinal type. Diffuse carcinoma is
      associated with proliferation of glandular epithelium (parietal, endocrine,
      cervical) due to genetic factors, hypergastrinemia caused by fundal gland
      atrophy, alkalization of the mucosa due to Helicobacter pylori infection.

PMID- 11534188
TI  - [Radiogenic (Chernobyl) thyroid cancer].
AB  - Thyroid carcinoma is a documented medical consequence of the Chernobyl accident,
      but medicobiological and other aspects of this problem are not yet understood
      completely because Chernobyl thyroid carcinoma (CTC) is not a single nosological
      entity but an integrated notion including various groups of population of
      different age and sex, pollution of the territory, various histogenesis (A-, C
      cells) and morphogenesis, latent period (minimal 4 years, maximal not yet known),
      variable clinical and morphological manifestations. Further CTC studies are
      needed on a special long-term program.

PMID- 11534189
TI  - [Histiocytic lesions of the orbit and eye appendages].
AB  - 2 cases of sinus histiocytosis with massive lymphadenopathy are reported. The
      disease belongs to non-neoplastic lesions associated with proliferation of
      histiocytes with antigen-treating function. A case of sarcoma is also described.
      It consisted of follicular dendritic cells related to histiocytes with the
      antigen-representing function.

PMID- 11534190
TI  - [Disruption of intercellular contacts and cell-extracellular matrix interaction
      in rapidly growing murine hepatocarcinoma].
AB  - A rapidly growing anaplastic variant spontaneously separating from differentiated
      transplanted hepatocarcinoma of mice differed from the parental tumour by a
      severe reduction of intercellular contacts, by alteration of interaction with
      extracellular matrix (ECM), speed of growth, loss of cell polarity and expression
      of some specific liver proteins. Almost all the cells in the parental tumor
      directly contact with ECM and, besides this, the tumor cells are surrounded by
      collagens of type I and IV. The majority of the cells in the rapidly growing
      tumor do not contact with matrix fibrillae. Cell culture of this variant retained
      its characteristics. Culture cells synthetize all the matrix components studied
      but collagens of type I and IV are lacking between matrix deposits. The critical
      stage responsible for the phenotypic changes in the anaplastic variant seem to be
      the disturbances in the system of integrins, reacting with collagens, in
      particular.

PMID- 11534191
TI  - [Clinico-anatomic analysis of maternal mortality in the Arkhangelsk region].
AB  - Clinico-anatomical analysis is presented of 93 autopsies of pregnant women, women
      in childbirth and puerperas who died in 1985-1999 in the Arkhangelsk region. In
      this region complications after abortion occur less frequently than in Russia on
      the whole while the percentage of late gestosis, obstetric hemorrhage and
      pyoseptic complications were high than mean Russian. In small number of
      discrepancies between final clinical and anatomo-pathological diagnosis, high
      percentage of discrepancies was found in the diagnosis of the 3rd category and
      iatrogenia this being due to difficulties in clinical diagnosis of obstetic
      pathology and increasing incidence of surgical deliveries.

PMID- 11534192
TI  - [Quality of clinical diagnosis in infants under one year of age according to
      autopsy data].
AB  - An analysis of quality of clinical diagnosis of causes of death in infants (under
      1 year of life) has been performed basing on the records of 1130 autopsies made
      in 1981-1998. The diagnosis accuracy, sensitivity, specificity and other quality
      characteristics have been assessed. The highest accuracy of clinical diagnosis
      has been found in respect of malformations, fetal hypoxia and natal asphyxia
      (0.94-0.84). Clinical diagnosis of birth trauma was less precise (0.61). Complex
      problems of perinatal pathology diagnosis are enlighted. Further improvement in
      its detection and identification is necessary.

PMID- 11534193
TI  - [Immunocompetent cells in decidual tissue in normal pregnancy and in cases of
      early miscarriages].
AB  - Uterine scrapes from 45 women (30 cases of spontaneous and 15 cases of artificial
      abortions) were studied. Heterogeneity of distribution of large granular
      lymphocytes and macrophages in decidual membrane of women with spontaneous
      abortions was revealed. Autoimmune disturbances were found primarily in the
      subgroup with domination of large granular lymphocytes, urogenital infection
      prevailed in the subgroup with macrophage domination. Hormonal disturbances and
      uterine malformations occurred more frequently in women with normal count of
      lymphocytes and macrophages.

PMID- 11534194
TI  - [Quality of clinical diagnosis: pathological-anatomical criteria].
AB  - In addition to discrepancy of clinical and anatomopathological diagnosis the
      author proposes several other criteria for assessment of quality of clinical
      diagnosis: hypo- and hyperdiagnosis, diagnosis of lethal complications, late
      diagnosis of the basic disease and fatal complications, diagnosis of iatrogenic
      complications, accuracy of formulation of the fanal diagnosis, use of biopsies
      for specification of clinical diagnosis and control of the patients' treatment.
      Complete computerization of the pathologist's workplace makes all these criteria
      most effective.

PMID- 11534195
TI  - [Pathohistological characteristics of dermatophytic onychomycosis].
AB  - A pathohistological study was made of the tissues taken from the distal phalanx
      of the great toe of 30 dead bodies with clinical picture of mycotic infection of
      nail plates. Onychomycosis was confirmed by the presence of pathogenic fungal
      myceliem detected microscopically. It is established that the fungus, in total
      onychomycosis, penetrates from the nail plate into the skin epidermis, connective
      tissue, bone and into the bone marrow of the phalanx. Cyst formation was found
      deep in the prickle-cell layer. Inflammation was rather weak reflecting a weak
      reactive response to the fungus presence.

PMID- 11534196
TI  - [Pagetoid reticulosis].
AB  - Pagetoid reticulosis is a rare form of T-cell skin lymphoma. A case of this
      disease is reported.

PMID- 11534197
TI  - [Morphometric and immunohistochemical markers of breast cancer progression].
AB  - The results of the study for the last decade aimed at the search of markers of
      mammary carcinoma malignancy and prognosis are reported. Accumulation and
      integration of various data contributes not only to more precise identification
      of the malignancy but also to more complete understanding of biological essence
      of mammary carcinoma.

PMID- 11534198
TI  - [Analysis of fatal outcomes according to the Moscow pathology service data (1996
      2000)].
AB  - The author presents the rate and structure of mortality in Moscow, the trend in
      the number of autopsies and analysis of lethal outcomes in Moscow for 5 years
      (1996-2000) vs those in Russia and abroad. Main causes of death were
      cardiovascular diseases (58%), malignant tumors (18%), traumas and poisoning
      (13%) and, according to the autopsy findings, alcohol-associated lesions of
      different organs (9%). Autopsy in Moscow was made in 43-48% of the deceased, in
      Russia--in 23-25%. Lack of clinical and postmortem diagnosis coincidence was 16
      17% in hospitals and 48-56% for non-hospitalized patients.

PMID- 11534199
TI  - [Adaptive effects of hypoxic preconditioning in brain neurons].
AB  - A preventive short-term hypoxia (preconditioning) increases neuronal resistance
      against subsequent strong hypoxic effects. Literature review and authors' own
      data on molecular-cellular mechanisms of the hypoxic preconditioning, are
      presented. Participation of intracellular signal transduction, genome, stress
      proteins, and neuromodulating peptides in this process, is discussed. The role of
      glutamatergic as well as calcium and phosphoinositide regulatory systems and
      neuromodulating factors as the components of a "volume" signal transmission are
      analyzed in hypoxic precondition-associated induction of functional tolerance
      mechanisms against acute harmful effects in neurones of olfactory slices.

PMID- 11534200
TI  - Influence of postweaning social isolation in the rat on brain development,
      conditioned behaviour and neurotransmission.
AB  - There is substantial evidence that early life events influence brain development
      and subsequent adult behaviour and play an important role in the causation of
      certain psychiatric disorders including schizophrenia and depression. The
      underlying mechanism of the effects of these early environmental factors is still
      not understood. It is a challenge to attempt to model early environmental factors
      in animals to gain understanding of the basic mechanisms that underlie the long
      term effects. This paper reviews the effects of rearing rats from weaning in
      social isolation and reports some recent results indicating hippocampal
      dysfunction. Isolation rearing in rats from weaning produces a range of
      persistent behavioural changes in the young adult, including hyperactivity in
      response to novelty and amphetamine and altered responses to conditioning. These
      are associated with alterations in the central aminergic neurotransmitter
      functions in the mesolimbic areas and other brain regions. Isolation-reared rats
      have enhanced presynaptic dopamine (DA) and 5-HT function in the nucleus
      accimbens (NAC) associated with decreased presynaptic 5-HT function in the
      frontal cortex and hippocampus. Isolation-reared rats have reduced presynaptic
      noradrenergic function in the hippocampus, but have enhanced presynaptic DA
      function in the amygdala. These neurochemical imbalances may contribute to the
      exaggerated response of the isolated rat to a novel stimulus or to stimuli
      predictive of danger, and isolation-induced behavioural changes. These changes
      have neuroanatomical correlates; changes which seem to parallel to a certain
      degree those seen in human schizophrenia. A greater understanding of the
      processes that underlie these changes should improve our knowledge of how
      environmental events may alter brain development and function, and play a role in
      the development of neuropsychiatric disorders.

PMID- 11534201
TI  - [Heterochronic effects of neurotrophic factors in neurochemical organization of
      learning and memory in the adult organism].
AB  - Following elaboration of long-term habituation to a startle-response, antibodies
      to neurotrophic factor protein S100b exerted selective and dose-dependent
      influence on different learning processes and memory of learned behavioural
      patterns in adult rats. S100b increased at all stages of behavioural skill
      development in hippocampus, hypothalamus, frontal cortex, cerebellar hemispheres
      and vermis, basal ganglia.

PMID- 11534202
TI  - [Formation of transcription factors AP-1 during learning in Helix].
AB  - An increase in the DNA-binding activity for the AP-1-family factors was shown to
      occur after food aversion conditioning. Learning experiments in vitro enhanced
      the DNA-binding activity. Effects of simultaneous action of serotonine and
      calcium on activation of transcriptional AP-1 factors was suppressed by inhibitor
      of calcium/calmodulin-dependent protein-kinases KN62 as well as by inhibitor of
      MAP-kinases PD98059. The co-operative induction of transcriptional AP-1 family
      factors activation by serotonine-induced and calcium-dependent regulatory systems
      may be one of the mechanisms of aversive conditioning in the CNS of the land
      snail.

PMID- 11534203
TI  - [Rf 0.58 protein in Helix command neurons during learning].
AB  - At early stages of aversive conditioning in Helix, a most considerable increase
      in the acid brain-specific protein Rf 0.58 occurred in LPa3 and PPa3 neurones.
      Later the content of this protein decreased in the PPa3 but went on increasing in
      LPa3. In sham learning, the protein content did not increase so obviously. Hence
      the protein Rf 0.58 metabolism in individual neurones of the snail CNS correlates
      with the draw step of receptor and effector fields in avoidance conditioning.

PMID- 11534204
TI  - [Brain central regions in courtship sound production in Drosophila melanogaster].
AB  - There are debates about the function of the two main central brain structures of
      insects--mushroom bodies and the central complex--in the control of motor co
      ordination and triggering of different behaviour programs including sound
      production. To throw additional light onto this problem we analysed the
      parameters of the love song produced by 5-day old males courting for 5 minutes a
      fertilised CS female at 25 degrees C, in two wild-type strains of Drosophila
      melanogaster (Berlin and CS), hydroxyurea (HU)-treated flies (chemical ablation
      of the mushroom bodies) two mushroom body mutants (mbm1 and mud1), two central
      complex mutants (ccbKS127 and cexKS181) and a mutant cxbN71 with defects both in
      the mushroom bodies and in the central complex. It was found that the love song
      of HU-treated flies devoid of the mushroom bodies is very similar to that of wild
      type flies. In mbm1 and mud1 the main parameters of the song (interpulse
      interval, IPI, and train duration) are slightly shifted from those of wild type
      but the sharpness of tuning of the pulse oscillator is the same. The flies of all
      these strains are equal to wild-type strains in mating success (% of copulations
      with virgins in 10-min test). On the contrary, the songs of the central complex
      mutants differ from those of wild-type flies. First of all, the sharpness of
      tuning of the pulse oscillator is destroyed,--the IPIs become highly variable.
      The pulses often are much longer and polycyclic as in well known cacophony
      mutant. The mean duration of pulse trains is much shorter. The males of the
      mutant cexKS181 usually court violently, but in most cases abnormal sounds are
      produced. Both cexKS181 and ccbKS127 males are much less successful in matings in
      comparison to wild-type flies. One can conclude that the central complex plays
      probably a very important role in the control of singing, whereas the mushroom
      bodies are practically not involved in this function.

PMID- 11534205
TI  - [Learning ability and memory formation in the Drosophila mutants with defective
      central complex and mushroom bodies].
AB  - Drosophila proved to be a very convenient model for genetic dissection of
      learning and memory in a number of experimental paradigms. A battery of mutations
      affecting either different subdomains of the central complex (CC) or of the
      mushroom bodies (MBs) enable the elucidation of the role of these central brain
      structures in different forms of learning and memory formation. We tested the CC
      mutants cexKS181 and ccbKS127 and MBs mutants mud1, mbm1 and cxbN71 for their
      ability for learning and memory formation in the conditioned courtship
      suppression paradigm. All the mutants were able to learn but demonstrated
      different memory defects. While the ccbKS127 mutant was normal in respect to
      memory formation, the cexKS181 mutant was defective in 30-min. and 3-hour memory;
      mud1 demonstrated a reduced 3-hour memory.

PMID- 11534206
TI  - [Comparative study of four P-insertional memory-deficient Drosophila mutants].
AB  - The previously suggested physiological model of conditioned courtship suppression
      in Drosophila was experimentally supported through investigation into the
      behaviour of the mutant males in two tests: the memory retention test and the
      retraining test. The mutations disrupted both types of the conditioned
      connections predicted by the model: association between conditioned and
      unconditioned stimuli and association between the conditioned stimulus and the
      aversive motivational system mediating the response to the unconditioned
      stimulus. The third category of mutants (P95, P124) appears to disrupt the
      function of the aversive motivational system.

PMID- 11534207
TI  - [Early gene expression in the rat brain following administration of
      corticoliberin in the neostriatum].
AB  - Using in situ hybridisation with oligonucleotide probes, an expression of
      immediate early genes c-fos, jun B, c-jun, and NGFIA in the rat brain was studied
      following intrastriatal microinjection of corticotropin-releasing hormone (CRH).
      The hormone induced expression of c-fos, jun B, and NGFIA mRNAs in the
      neostriatum as well as in its target brain areas, including nucleus accumbens and
      different cortical areas. The expression of c-jun mRNAs was unaffected. The
      findings indicate that neuronal activation of the neostriatum and its target
      brain areas provides one possible mechanism for mediating adaptive CRH actions in
      stress.

PMID- 11534209
TI  - [Components of the intracellular cyclic AMP system maintaining olfactory
      reception of amyl alcohol].
AB  - In experiments on isolated olfactory epithelium, cAMP was shown to have an
      intracellular signal system which participates in pentanol olfaction
      transduction. Increase in the intracellular cAMP level is associated with
      adenylate cyclase activation due to G-protein stimulation by odorant coupled with
      it.

PMID- 11534208
TI  - [Neurite-stimulating effect of Hirudo medicinalis salivary gland secreting
      factors in organotypic culture of the dorsal root ganglia].
AB  - Effects of destabilise, bdellin, bdellin A, eglin were investigated in
      organotypic tissue culture of dorsal root ganglia (DRG) of 10-11-day old chick
      embryos. Native destabilase and bdellin A, bdellin B and eglin are more active
      inducing a more intensive neurite growth in DRG as compared with the control. A
      neurite-stimulating effect of the drug "pyjavit" seems to be associated with
      destabilase, bdellins and eglin neurite-stimulating activity.

PMID- 11534210
TI  - [ I P Pavlov principles of the higher nervous activity--a reliable basis for
      modern cognitive physiology].
AB  - The paper shows that formulated by I. P. Pavlov principles of higher nervous
      activity are quite fruitful even today in investigations into the problems
      associated with contemporary new physiological trends as, for instance, cognitive
      processes. Special attention is paid to study of the principles of
      neurophysiological organisation of the mechanisms carrying out analysing and
      synthesising activities. I. P. Pavlov was the first to indicate the important
      role of frontal cortex in these processes.

PMID- 11534211
TI  - [A specific function of the motor cortex in the reorganization of coordination in
      motor learning in animals and humans].
AB  - The findings suggest that a particular function of MCx in motor learning involves
      suppression of synergies and co-ordination which interferes with acquisition of
      new motor patterns. Experimental animal models based on inhibition of certain
      natural synergies or reflexes in the process of learning new co-ordination have
      been developed where the MCx is responsible for inhibition of natural motor
      patterns. Following the MCx lesion the natural synergies dominate again and the
      learned movement cannot be adequately performed. Similar disturbances occur after
      combined lesions of the premotor and parietal associative cortex or after lesions
      of the cerebellar nuclei. However, after the associative cortex or cerebellar
      lesions the recovery of learned co-ordinations is possible. This suggests the
      inhibition of inappropriate synergies or co-ordination during motor learning is a
      specific function of the MCx, the latter taking part in organisation of new co
      ordination between posture and movement in humans as well.

PMID- 11534212
TI  - [Effects of motivational and emotional factors on glutamate release in the
      nucleus accumbens of rats during feeding].
AB  - Food intake was shown to decrease the glutamate extracellular level in the
      nucleus accumbens in both deprived and non-deprived Spraque-Dawly rats. Feeding
      combined with presentation of a tone previously paired with foot shock caused an
      increase in the glutamate extracellular level in deprived rats only, whereas the
      tone alone had no effect. The data suggest that emotional and motivational
      variations exert co-operative effect on the glutamate release in the nucleus
      accumbens during feeding.

PMID- 11534213
TI  - [Analysis of structural basis of information processing in basal ganglia: spatial
      organization of the thalamo-striatal projections in the dog brain].
AB  - Distribution of neurones labelled in a retrograde way, studied in functionally
      different dog's thalamic nuclei, elucidated anatomical aspects of functional
      heterogeneity of the basal ganglia and of integrative information processing, as
      well as the organization of adaptive behaviour mechanisms.

PMID- 11534214
TI  - [Local and distributed neuronal networks and individuality].
AB  - To estimate stable behavioural peculiarities, an individual varying choice of
      greater or better appetite reinforcement depending on the time of instrumental
      motor response was used with cats. A decisive role in realisation of the response
      choice is played by the influence of motivational structures of hypothalamus and
      amygdala on formal areas of neocortex typical for "impulsive" (fast reacting)
      cats, and interaction of the frontal cortex--hippocampus system for the animals
      with delayed pressing of the lever to obtain their preferred food, i.e.
      manifesting the ability of "self-control".

PMID- 11534215
TI  - HR customer service--FedEx.com or BUST!
AB  - As the "customers" of the benefits department, employees, beneficiaries and
      retirees deserve best practice service delivery. This article describes a
      benefits administration operating model that can deliver high levels of customer
      service by furnishing accurate, consistent and timely information. Performance
      measurement is a key element in this type of customer satisfaction, particularly
      when outsourcing vendors are involved in the provision of benefits.

PMID- 11534216
TI  - Employee benefit plans need to protect privacy of participant information.
AB  - Employee benefit plans need to examine their privacy policies and practices.
      Three areas of privacy compliance plan administrators should review are the HIPAA
      privacy regulations, state law claims against employee benefit plans for invasion
      of privacy and Web site privacy policies.

PMID- 11534217
TI  - Promising strategies help employers integrate pharmacy and medical programs--and
      reap cost, quality advantages.
AB  - Providing quality pharmacy benefits while managing costs is an escalating
      challenge for employers. Easy solutions such as higher copays and standard three
      tier systems will not provide effective, long-lasting results that include
      improved clinical outcomes. Employers must concentrate on educating employees on
      the real cost and value of their pharmacy benefits and they must also take an
      integrated view of medical and pharmacy benefits.

PMID- 11534218
TI  - The Pregnancy Discrimination Act: employer health insurance plans must cover
      prescription contraceptives.
AB  - The Equal Employment Opportunity Commission (EEOC), which recently took the
      position that employer health plans are required, in many instances, to cover
      prescription contraceptives, has issued guidelines to assist employers in
      complying with the law prohibiting discrimination on the basis of sex and
      pregnancy. Employers should review these guidelines carefully in relation to
      their health care plans.

PMID- 11534219
TI  - Internet/Web-based administration of benefits.
AB  - Most funds will face the challenge of deploying at least some Web-based
      functionality in the near future, if they have not already done so. Clear
      objectives and careful planning will help ensure success. Issues that must be
      considered include support requirements, security concerns, functional business
      objectives, and employer and member Web access.

PMID- 11534220
TI  - Who is a fiduciary?--implications of Supreme Court rulings.
AB  - The determination of who is a fiduciary under ERISA is of extreme importance in
      assessing potential ERISA liability. The analysis used in making this
      determination once seemed clear, but that may no longer be the case in the wake
      of recent Supreme Court decisions that redefine the line between fiduciary and
      nonfiduciary conduct.

PMID- 11534221
TI  - Account-based retiree medical plans: what's good for your pension plan may be
      good for your retiree medical plan.
AB  - Many of the same forces that caused employers to gravitate toward account-based
      pension plans are beginning to spark similar changes in retiree medical plans. As
      medical costs continue to escalate, account-based retiree medical plans offer a
      new way to manage company outlays, while preserving an important benefit for
      retirees.

PMID- 11534222
TI  - A guide to understanding long-term care insurance.
AB  - Long-term care insurance is an increasingly popular benefit that has a number of
      advantages for both employers and employees. This coverage can protect employee
      assets and retirement savings and can be offered as a tax-free benefit if the
      plan is qualified. The premiums can be tax-deductible to employees, and the
      benefit is portable, since the policy is owned by the employee.

PMID- 11534223
TI  - When the fine print isn't so fine: reviewing contracts of health plan service
      providers.
AB  - Most employers delegate responsibilities for health plan administration to one or
      more service providers or vendors. Recent legal developments make it increasingly
      important for employers to ensure that the contracts with their vendors provide
      appropriate protections against liability, hold vendors accountable for
      performing the services they agree to provide and enable plans to comply with an
      ever-expanding list of federal and state law requirements.

PMID- 11534224
TI  - A revolutionary approach to health care cost control: leveraging the power of Web
      enabled employee "consumerism".
AB  - The confluence of two trends--health care "consumerism" and employee self-service
      benefits programs--offers employers a promising opportunity for health care cost
      control. To take advantage of this opportunity, employers must take a fresh look
      at the health care cost dilemma and find ways to simultaneously offer employees a
      new kind of benefit and implement more effective cost-control measures.

PMID- 11534226
TI  - Merits of clean steam.

PMID- 11534225
TI  - Reviewing efficacy of alternative water treatment techniques--Part 2.

PMID- 11534227
TI  - EWGLI faces political intervention.

PMID- 11534228
TI  - HTM 63 versus HTM 71--no contest!

PMID- 11534229
TI  - Comparing international experience.

PMID- 11534230
TI  - Hospital-based engineering services provide high value.

PMID- 11534231
TI  - Spotlighting cost management of building services.

PMID- 11534232
TI  - Pneumatic tube systems for ever-changing marketplace.

PMID- 11534233
TI  - A new vision for engineering.

PMID- 11534234
TI  - Installing safe and secure power.

PMID- 11534235
TI  - Strike that. Years after aborted initiative, Sharp HealthCare seeks to get name
      off Mexican hospital.

PMID- 11534236
TI  - Prompting promptness. Fines mount against seven insurance firms for dragging feet
      with payments.

PMID- 11534237
TI  - Maintenance firm in a fix. Suits against NeoDyme allege breach of contract.

PMID- 11534238
TI  - Eye on info. Advances boost care, imperil privacy.

PMID- 11534239
TI  - Eye on info. Controlling information access. Providers contend with balancing
      act.

PMID- 11534240
TI  - Eye on info. Security costs, savings. Compliance expenses buy benefits.

PMID- 11534241
TI  - Eye on info. The technology behind it. The challenge of pulling it all together.

PMID- 11534242
TI  - Eye on info. Sage page. Security an issue long before HIPAA.

PMID- 11534243
TI  - Who holds the cards in healthcare poker?
AB  - Healthcare has always been a tricky game in Washington. Reaching consensus has
      often been almost impossible. Now, two months after James Jeffords defected from
      the Senate GOP fold, handing control to the Democrats, shifting coalitions are
      creating an even more volatile environment.

PMID- 11534244
TI  - Benefis tries again. New competitor spurs Mont. system to seek further relief
      from merger rules.

PMID- 11534245
TI  - Don't tell, don't ask. Inspector general's report rips PRO oversight.

PMID- 11534246
TI  - Don't tell, don't ask. By the way, you have a new inspector general.

PMID- 11534247
TI  - On an upswing. AHA's dues picture brightens a bit.

PMID- 11534248
TI  - Take us to a leader. AMA seeks member help in national search for 'proven' chief
      executive.

PMID- 11534249
TI  - 'We have to sacrifice'. States offer to pick up the tab for unpaid leave.

PMID- 11534250
TI  - There she is, your ideal.

PMID- 11534251
TI  - The new green game.

PMID- 11534252
TI  - Hospital legacies. Tale of the unexpected.

PMID- 11534253
TI  - Hospital reconfiguration. Going places.
AB  - Two major hospital moves in Lanarkshire were completed smoothly by predicting the
      number of emergency admissions likely over the crucial periods and involving GPs
      and all the hospitals concerned. An analysis of emergency admissions was one
      factor in deciding which days the moves should take place on. A workshop after
      the first move was finished proved important.

PMID- 11534254
TI  - Open space. Vision from afar.

PMID- 11534255
TI  - Frontline staff. A winter's tale.

PMID- 11534256
TI  - Classification criteria for antiphospholipid syndrome.
AB  - The major purpose of the 1999 international consensus criteria for definite
      antiphospholipid syndrome (APS) is to facilitate the selection of uniform groups
      of patients for clinical and experimental studies. An early evaluation suggests
      that the criteria fulfill this purpose when tested in patients with systemic
      lupus erythematosus or lupus-like diseases. The criteria will likely need
      modification as investigators appraise and reach consensus about new information
      on APS. The international APS symposium has had an important role in this process
      and provides a mechanism for facilitating future advances in this subject.

PMID- 11534257
TI  - Hughes (antiphospholipid) syndrome. Clinical features.
AB  - Hughes (antiphospholipid) syndrome is a noninflammatory autoimmune disease. The
      most critical pathologic process is thrombosis, which results in most of the
      clinical features suffered by these patients. Recurrent thrombosis together with
      an adverse pregnancy history and the presence of antiphospholipid antibodies
      defines the syndrome.

PMID- 11534258
TI  - Which antiphospholipid antibody tests are most useful?
AB  - Despite an active international effort to improve diagnosis and treatment of the
      antiphospholipid syndrome (Hughes syndrome), there remain problems of lack of
      standardization and lack of prospective and multivariate epidemiologic analysis
      which restrict the diagnostic and predictive ability of commercially available
      tests. Nevertheless, current published series provide some data from which
      strategic approaches can be used to maximize the efficiency and usefulness of
      available tests. For further updates on new research and developments of interest
      to physicians and patients with this syndrome, the following web sites may prove
      helpful: www.slrapls.org, www.hematology.org, www.acforum.org,
      www.americanheart.org, www.rarediseases.org, www.aarda.org, and www.lupus.org.

PMID- 11534259
TI  - Origin of antiphospholipid antibodies.
AB  - Our observations and those from others give further support to our hypothesis
      that "autoimmune aPL" may be generated by immunization with products from
      bacteria or viruses after incidental exposure or infection. We also were able to
      generate an APS-like syndrome in a strain of mice susceptible to autoimmunity,
      indicating that other factors such as genetic factors are likely to be involved
      in development of APS. Furthermore, not all aPL generated by immunization with
      bacterial or viral products were pathogenic. Based on the clinical experience and
      on the numerous reports indicating the presence of aPL in large number of
      infectious diseases, it may be expected that not all aPL produced during
      infection are pathogenic. We hypothesize that a limited number aPL induced by
      certain viral or bacterial products would be pathogenic in certain groups of
      predisposed individuals. Identification of those bacterial or viral agents may
      help to find strategies for the prevention of production of "pathogenic" aPL.
      Alternatively, free peptides may be used to induce tolerance against aPL
      production.

PMID- 11534260
TI  - Genetics of antiphospholipid syndrome.
AB  - The mechanisms of thrombosis in antiphospholipid syndrome (APS) are highly
      heterogeneous and multifactorial, and some genetic factors may be involved in its
      pathophysiology. The genetic variants of representative antigen, beta 2
      glycoprotein I (beta 2GPI), have been known, and valine/leucine247 polymorphism
      is a genetic risk for having anti beta 2GPI antibodies and APS. Congenital beta
      2GPI deficiency did not correlate with thrombophilia, thus its responsible gene
      (beta 2GPI-Sapporo) was not a risk for thrombosis. Many other thrombosis-related
      genetic factors have been investigated in APS, but no additional risk for
      thrombosis has been indicated in patients with antiphospholipid antibodies.

PMID- 11534261
TI  - Antiphospholipid antibodies and the coagulation cascade.
AB  - Hemostasis is a highly controlled system of associated biophysical and
      biochemical events requiring a number of molecular and cellular interactions,
      among which molecular assembly at surfaces is an obligatory mechanism. The
      exposure of flowing blood to subendothelial components results in platelet
      adhesion, activation, and aggregation with simultaneous exposure of negatively
      charged phospholipids, which serves as a template for the formation of enzyme
      cofactor-substrate complexes. The locally formed proteases activate surface-bound
      zymogens in a sequence culminating in the formation of thrombin. Fibrinogen is
      transformed into fibrin by thrombin, which may also activate protein C on
      phospholipid membranes when bound to TM. Activated protein C is a potent
      anticoagulant that inactivates coagulation-activated cofactors Va and VIIIa.
      During this process, proteins bound to the phospholipid surfaces may adopt new
      configurations and expose neoepitopes, which may elicit an immunologic response
      giving rise to the generation of antiphospholipid antibodies. These antibodies
      may then interfere with the procoagulant or anticoagulant activities of the
      target protein-phospholipid complexes. The apolipoprotein beta 2GPI and
      prothrombin are the most frequently found cofactors for antiphospholipid
      antibodies. Components of the protein C pathway have also been identified as
      cofactors. The pathophysiologic effects of antiphospholipid antibodies on the
      thrombotic accidents observed in patients with the antiphospholipid syndrome have
      not been established yet.

PMID- 11534262
TI  - Antiphospholipid antibodies and the endothelium.
AB  - The interaction between aPL (particularly anti-beta 2GPI antibodies) and
      endothelium does represent a potential pathogenetic mechanism for the thrombotic
      manifestations of the syndrome. The autoantibody-mediated EC activation probably
      plays a role in sustaining the appearance of a proadhesive, proinflammatory, and
      procoagulant phenotype. The heterogeneity of the APS clinical manifestations is
      likely linked to the varied effects that aPL can induce on ECs and to the
      different functions that ECs display depending on the anatomic localization.

PMID- 11534263
TI  - Accelerated atheroma, antiphospholipid antibodies, and the antiphospholipid
      syndrome.
AB  - Indirect data coming from animal studies and in vitro observations support the
      contention that the mere presence of antiphospholipid antibodies may be
      sufficient to increase atheroma development, regardless of other predisposing
      factors. It seems that humoral and cellular immune responses to beta 2
      glycoprotein I can play an important role in mediating the increased propensity
      to atherosclerosis.

PMID- 11534264
TI  - Antiphospholipid antibodies. Risk assessments for solid organ, bone marrow, and
      tissue transplantation.
AB  - The literature pertaining to transplantation of solid organs, bone marrow, and
      other tissues in aPL-positive patients has been reviewed. The effects that aPL
      have relative to BMT are altogether different than those ascribed to solid organs
      and tissues. By definition, the transplantation of allogeneic bone marrow serves
      to reconstitute the recipient with a completely new and genetically different
      repertoire of antibody-producing cells. Previously aPL-positive bone marrow
      recipients become aPL-negative subsequent to transplantation assuming that the
      marrow donor is aPL-negative. These observations are the basis for contemporary
      experimental approaches to curing certain autoimmune diseases with BMT.
      Similarly, it would follow that an aPL-negative patient provided cells from an
      aPL-positive donor could become aPL-positive and suffer increased risk for
      thrombosis. From the data provided in most of the non-bone marrow publications,
      the presence of aPL should be considered a grave risk factor for any potential
      solid organ or tissue transplant candidate. Peritoneal dialysis patients seem to
      be at maximal risk. Given the serious emotional and economic impact of
      irreversible thrombotic loss suffered by organ transplant recipients, these
      factors alone should justify the modest expense of pretransplant aPL screening.
      In the United States, the average cost of losing a kidney transplant to aPL
      associated thrombosis was estimated from 1996 data to be $82,000. The cost of
      losing a heart or liver is measured not only in dollars but often in the
      patient's life. The encouraging news, however, is that once aPL are identified
      before transplantation, prophylactic anticoagulation seems to be capable of
      forestalling untoward aPL-associated allograft events. Clearly, much remains to
      be discovered in exploring the pathobiologic characteristics of aPL in the
      laboratory as well as in neutralizing their procoagulant effects at the bedside.

PMID- 11534265
TI  - Management of thrombosis in antiphospholipid antibody syndrome.
AB  - Antiphospholipid antibody positive patients are at risk for venous and arterial
      thrombosis. The risk of recurrent thromboembolism is high. Although the standard
      of care is high-intensity warfarin after a thromboembolic event, some studies
      indicate that this degree of anticoagulation is not needed. There is an urgent
      need of clinical trials to address management of thrombosis in antiphospholipid
      syndrome.

PMID- 11534266
TI  - Management of pregnancy in antiphospholipid syndrome.
AB  - Pregnant women with APS are at high risk of maternal and fetal pregnancy
      complications. Multidisciplinary teams expert in this condition should coordinate
      management. Even with current management strategies, the risk of maternal
      thrombosis, fetal loss, or other adverse obstetric outcomes remains. Close
      monitoring of the various aspects of this condition may reduce maternal morbidity
      and improve fetal outcome. The pathogenesis of the adverse pregnancy outcome in
      APS has not yet been fully elucidated, although active research in this field
      continues. Until this is ascertained, we must accept that many aspects of
      management are purely empiric, and it is our duty to counsel patients thoroughly
      so that they understand the risks and benefits of the treatment options they are
      offered.

PMID- 11534267
TI  - Prognosis in antiphospholipid syndrome.
AB  - The results of prospective large cohort studies of patients with different
      clinical subsets of APS have been reported recently. A significant impact of the
      disease on long-term survival has been documented in these studies. Cumulative
      irreversible damage secondary to thrombosis results in organ dysfunction and
      morbidity. To assess prognosis and treatment in APS, it is imperative to quantify
      damage. We have recently created and validated an Antiphospholipid Damage Index,
      which is currently undergoing improvements. Having APS, whether primary or
      secondary, definitely confers a poor prognosis.

PMID- 11534268
TI  - [Causes of ambiguous external genitalia in neonates].
AB  - INTRODUCTION: The classification of disorders such as ambiguous genitalia in
      newborns is difficult because similar or identical phenotypes could have several
      different aetiologies. In most cases it was impossible to correlate the aetiology
      of the disorder and the appearance of the external genitalia [1-3]. A newborn
      with ambiguous genitalia needs prompt evaluation that will permit gender
      assignment and detection of life-threatening conditions (salt-losing crisis due
      to congenital adrenal hyperplasia or Wilms' tumour). We studied the causes and
      characteristics of ambiguous genitalia in newborn infants over the period from
      1990 to 1999. PATIENTS AND METHODS: The following genital phenotypes are
      considered as ambiguous: 1. Hypospadias with no palpable gonads; 2. Hypospadias
      with micropenis and no palpable gonads or one palpable gonad; 3. Newborn with
      female external genitalia and a gonadal mass in labia or labial fusion and/or
      clitoral enlargement [1, 4]. The diagnostic evaluation of newborns with ambiguous
      genitalia consisted of history and physical examination, determination of serum
      electrolytes, plasma 17-hydroxyprogesterone (17-OHP), chromosome analysis on
      cultured lymphocytes, sonogram of the abdomen in connection with a genitogram;
      and whenever it was necessary, basal plasma concentrations of testosterone and,
      after the stimulation with human chorionic gonadotropin (hCG), laparotomy for
      definitive determination of gonadal histology. All disorders with ambiguous
      genitalia have been classified in four groups: [6]: 1. Female
      pseudohermaphroditism (FPH); 2. Male pseudoherma phroditism (MPH); 3. True
      hermaphroditism (TH); 4. Asymmetrical gonadal dysgenesis (ASGD). RESULTS: The
      causes of sexual differentiation disorders in a group of 38 newborns with
      ambiguous genitalia are presented in Table 1. Main criteria for the diagnosis of
      FPH were normal female karyotype 46, XX, masculinization of external genitalia
      and no palpable gonads. Genitography revealed urogenital sinus and vagina, and
      ultrasound examination the uterus. During initial examination seven of 15
      newborns with congenital adrenal hyperplasia (CAH) (Table 2) due to 21
      hydroxylase (P450c21) deficiency (21-OHD) had clinical or laboratory signs of
      adrenal crisis. Two children had a simple virilizing form of 21-OHD. The female
      gender was chosen for these children. In other three patients with FPH isolated
      clitoral hyperplasia or labial fusion was the main reason for the studies. The
      common characteristics of newborns with MPH were as follows: normal male
      karyotype 46,XY with normally developed or dysgenetic testes, and/or good
      response to hCG stimulation. The complete androgen insensitivity (testicular
      feminization) was detected in two children (Table 3) with female external
      genitalia and palpable gonads in the labial folds, and female gender was chosen.
      The Denys-Drash syndrome was detected in one newborn with ambiguous genitalia, no
      palpable gonads, and normal response to hCG, and ultrasound findings of multiple
      bilateral renal tumours were identified as Wilms' tumour. In other newborns with
      MPH incomplete masculinization consisted of hypospadias, mostly of perineoscrotal
      type and of micropenis (penile size less than 2 cm) and/or bilateral or
      unilateral cryptorchidism (Table 3). In all children male sex was chosen.
      Asymmetrical gonadal dysgenesis was detected in two newborn infants. Both
      children had 46,XY/46,XX karyotype, testes on one side of the abdomen, and streak
      gonad on the other, developed vagina, uterus and unilateral Fallopian tube, and
      were raised as females. True hermaphroditism was established in one newborn with
      46,XX karyotype, with a testis on one side of the abdomen and an ovotestis on the
      other side. The parents decided for male gender. The aetiology of ambiguous
      genitalia was not established in five children; in two children with 46,XY and
      one with 46,XX karyotype (with palpable gonads) the diagnostic study was not
      completed. CONCLUSIONS: The most common cause of ambiguous genitalia in our
      newborn patients was CAH due to 21-OH deficiency [2, 4, 6, 7]; 87 percent of
      patients had salt wasting form of the disease. In the majority of patients the
      appearance of the external genitalia made possible the detection of the disease
      immediately after the birth. So, the relative high incidence of adrenal crisis in
      our patients with CAH (38%) seems unreasonable. The decision for gender
      assignment was possible after the appropriate study of the nature of the
      disorder. The causes of MPH are numerous and heterogeneous [1, 3, 8]. With the
      exception of two patients with complete form of androgen insensitivity, in all
      newborns with MPH the male gender predominated. The appearance of external
      genitalia with severe perineoscrotal hypospadia and/or micropenis suggested the
      possibility of incomplete androgen resistance. If a male assignment is being
      considered, the response of the phallic size to treatment with testosterone was
      recommended. If penile size did not reach the 2.5 cm range or above, a male sex
      assignment was not advisable [1]. It is important for the paediatric surgeon to
      be involved in the diagnostic evaluation of these infants to plan the timing and
      techniques of the surgical reconstruction [6]. The decision to raise a patient
      with sex chromosome mosaicism, true hermaphroditism, or mixed gonadal dysgenesis
      as either a male or a female was based on the appearance of the external
      genitalia and possible fertility [1, 9]. The parental decision of male sex in our
      patients with true hermaphroditism could not be considered as optimal.

PMID- 11534269
TI  - [Incidence and severity of degenerative changes in the wrist in pseudoarthrosis
      of the scaphoid bone]].
AB  - INTRODUCTION: In patients with symptomatic scaphoid nonunion there was an
      increased evidence of progressive osteoarthrosis expressed as instability of the
      wrist [1, 2]; it is defined as a scapholunate angle of more than 70 degrees or a
      radiolunate angle of more than 10 degrees. Intercarpal instability causes
      unnatural joint movement of the wrist. This disorganization of the wrist
      mechanism associated with hypermobility of the schapoid bone induces degenerative
      changes [3]. Arthritic changes begin at the distal scaphoid-radial styloid joint
      and later progress to the capitolunate joint. A similarity was noted with
      rotatory instability of the scaphoid bone associated without fracture [2]. If mid
      carpal joint exists the joint becomes unstable, the lunate rotates backwards and
      carpal bones show the so-called concertina deformity [4] or dorsal intercalated
      segment instability pattern [5]. AIM: We tried to determine the factors of risk
      and prognostic indicators of degenerative arthritis. METHOD: In this study 40
      patients with painful nonunion of the scaphoid bone were analysed. Duration of
      nonunion was 1.43 year (range from 8 months to 15 years). Roentgenograms of the
      hand were done in anteroposterior, lateral and oblique projections. Fracture
      location and configuration were determined as described by Russe. Instability was
      determined by measuring the scapholunate and radiolunate angle in the lateral
      roentgenogram. Scapholunate angle more than 70 degrees and radiolunate angle more
      than 10 degrees were considered abnormal. To asses the amount of carpal collapse
      the carpal index was determined as described by Youm [6]. Abnormal value was 0.50
      or less (normal value: 0.54 +/- 0.03). Four roentgenographic groups were
      established based on the extent of degenerative changes [7]. Group I showed no
      sign of degenerative changes. Group II had sclerotic lesions in fracture margins
      with or without a cystic formation. Group III showed lesions of radioscaphoid
      arthritis, including joint-space narrowing and pointing the radial styloid. Group
      IV had lesions of generalized arthritis of the wrist. RESULTS: Duration of
      nonunion was not in correlation with development of osteoarthritic changes (p =
      0.644, p > 0.05) (Table 1). Progressive degenerative changes correlated well with
      radiolunate angle (p = 0.398, p < 0.05), capitolunate angle (p = 0.381, p < 0.05)
      and carpal index (p = 0.392, p < 0.05) (Table 2). The average values of
      intercarpal angles increased with progression of osteoarthritic changes (Table
      3). There were 14 (35%) proximal third located fractures and 26 (65%) in the
      middle third or waist. There was a statistically strong correlation between
      location of the fracture in proximal third and presence of degenerative changes
      (p = 0.341, p < 0.01) (Table 4). Intensity of arthritic changes showed no
      statistically significant correlation regarding untreated fractures (p = 0.665, p
      > 0.05). DISCUSSION: In our study the most significant factors associated with
      arthritis were instability of the wrist and fracture location at the proximal
      third of the scaphoid bone. Mack [7] reviewed forty-seven symptomatic nonunions
      of the scaphoid and found a correlation between the presence of arthritis and the
      duration of nonunion. Also, he concluded that instability of the wrist can occur
      as late phenomenon in previously stable nonunion. Similar results were noted by
      Ruby [8] in his series. Conclusion of these authors was that the incidence of
      degenerative changes increased with the time after fracture of the scaphoid bone
      occurred [8-12]. We demonstrated that in untreated fractures associated with
      carpal instability, arthritis developed much earlier. Fourteen (35%) patients in
      our study were not treated and 92.8% belonged to Group II and Group III, with
      average time of nonunion duration of 27.2 months. Lunate dorsiflexion is a useful
      guide to carpal instability. In our experience the lunate silhouette is easily
      visualized on a lateral roentgenogram even in the presence of degenerative
      arthritis. There is a high probability that degenerative changes will occur. We
      recommend that a scaphoid nonunion associated with carpal instability should be
      operated before degenerative changes develop.

PMID- 11534270
TI  - [Epidemiologic characteristics of insulin-dependent diabetes mellitus].

PMID- 11534271
TI  - [The internal thoracic artery; superior histologic, physiologic and endothelial
      characteristics as a superior graft].

PMID- 11534272
TI  - [Classification of cerebrovascular diseases].

PMID- 11534274
TI  - [Biomechanics of the meniscus of the knee joint and its characteristics].

PMID- 11534273
TI  - [Basis for classification of drug-induced risks for spermatogenesis and outcome
      of pregnancy].

PMID- 11534275
TI  - [Arthroscopy and its importance in the diagnosis of lesions of the meniscus].

PMID- 11534276
TI  - [History of endocrinology at the Medical School of Belgrade].

PMID- 11534277
TI  - [Effect of slow repetitive transcranial magnetic stimulation on depression in
      patients with Parkinson disease].
AB  - Parkinson's disease (PD), that has usually been associated with movement
      disorders, is also associated with depression in about 40% of patients [1-9].
      Transcranial magnetic stimulation (TMS) is a new non-invasive technique for
      direct stimulation of the cerebral cortical neurons [1]. Several open studies
      have shown that repetitive TMS (rTMS) at both rapid (rapid rTMSi > 1 Hz) and low
      frequencies (slow rTMSi < 1 Hz) may have antidepressant action [2-6]. The study
      included 8 patients diagnosed as PD fulfilling the DSM-IV criteria for major
      depression (5 patients) and dysthymia (3 patients). Magnetic stimulator, 200 Mag
      Stim, total output 2 T and a circular coil of 90 mm, were used. For ten
      consecutive days, between noon and 1 p.m. the patients were stimulated with
      apprx. 80% of the output (1.6 T) at 0.5 Hz. The daily treatment implied
      stimulation of both sides of the head (first the right, then the left) at four
      sites (prefrontal, frontal, parietal and occipital regions) with 5 stimulations
      each site (20 stimulations per hemisphere). Before the beginning of the study, 2
      3 hours after the last stimulation (day 10), 7 and 14 days after completion of
      the treatment, the patients were subjected to scoring on the Hamilton Depression
      Rating Scale [11] and Unified Parkinson's Disease Rating Scale (UPDRS) [12]. The
      HDRS values before initiation of rTMS were 19.2 +/- 3.1, with significant fall (p
      < 0.01) after 10 days of stimulation (14.9 +/- 3.2), 17 days (12.2 +/- 2.7) and
      24 days (13.6 +/- 5.3) after the beginning of the study, suggesting that the
      antidepressive effect persisted even two weeks after discontinuation of
      stimulation. The UPDRS values were monitored concomitantly. The values on this
      scale failed to alter significantly. In conclusion, rTMS is a relatively safe and
      painless method associated with antidepressant action in PD patients. Treatment
      of depression in PD is of great importance, but the choice of medication is
      accompanied with numerous limitations [20]. Antidepressant action of rTMS and its
      maintenance for two weeks after discontinuation of stimulation enables usage of
      this method in PD in phases of exacerbation of depressive symptoms at least over
      the period required to reach the full effect of selected medication.

PMID- 11534278
TI  - [Differential diagnosis of deep vein thrombosis].
AB  - The incidence of deep venous thrombosis (DVT) is high in numerous surgical and
      medical diseases [1]. There are increasing data on higher incidence of DVT in
      patients with malignant and other diseases [2]. The diagnosis of DVT is not
      always simple since there are subclinical and asymptomatic forms of the disease
      [3]. Besides, there are numerous pathological conditions that imitate deep venous
      thrombosis [4]. METHODS: We present the results of a retrospective study over the
      period of January 1, 1996--June 30, 1998 at the Department of Vascular Surgery.
      Over that period we treated 113 patients (64 females, 49 males, average aged 60.3
      +/- 7.5 years) with clinical picture of deep venous thrombosis. All patients
      underwent duplex scanning examinations (Toschiba SSA-100 A, 3.5 MHz and 8 MHz
      probes) [5, 6]. Special examinations such as angiography (8 patients),
      computerised tomography or nuclear magnetic resonance (27 patients) were
      performed in cases with unclear findings. RESULTS: True DVT was established in 91
      (80.3%) patients (Fig. 1). Seven of these patients had asymptomatic
      phlebothrombosis. Of 12 (10.6%) patients in 9 other pathologic conditions were
      found (Fig. 2). This symptomatic DVT was caused by malignant diseases (5
      sarcomas, 2 metastatic carcinomas, 1 lymphoma); aneurysms of common femoral
      artery (2) and popliteal artery (2 patients). Ten patients (8.9%) with clinical
      picture of DVT established by special examinations had no evidence of the
      presence of intravenous thrombs (Fig. 3). This pseudo DVT was caused by calf
      haemathoma (3), Baker's cyst (2), popliteal artery aneurysm (1), lipoma of thigh
      (1), psoas abscess (1), gluteal abscess (1) and acute arthritis of the knee (1).
      The treatment of these groups of patients was different: surgical thrombectomy,
      use of streptokinase or heparine (true deep vein thrombosis), tumour extraction
      (Fig. 4) or another surgical treatment (symptomatic phlebothrombosis) and special
      decompression measures (Fig. 5) (pseudophlebothrombosis). DISCUSSION:
      Aetiopathogenesis of true DVT is determined by Virchov's triad [3, 4, 7, 8]. The
      incidence of DVT in medical and surgical patients is high (30-75%). Initially
      true DVT may be asymptomatic in 35-70% of patients [1, 3, 8] and depended on
      detection methods [1, 6, 7, 9, 10]. DVT may be only a symptom of other
      pathological conditions [2, 3, 7]. This symptomatic DVT is mostly caused by
      malignant diseases [2]. Pseudo DVT or primary deep vein obstruction may be caused
      by external abnormalities (right common iliac artery; compression of the left
      common iliac vein, malignant disease, retroperitoneal fibrosis, internal iliac
      compression of the external iliac vein, latent femoral hernia compression of the
      femoral vein, masses in the thigh (large tumours, true or false aneurysms,
      popliteal masses/aneurysms, large Baker's cysts), changes in the wall or within
      the lumen of a vein as aplasia, primary tumours, intraluminal spurs [7].

PMID- 11534279
TI  - [Diagnostic value of hysterosalpingography in examination of Fallopian tubes in
      infertile women].
AB  - Hysterosalpingography (HSG) is a radiographic examination of endocervical canals,
      uterine cavity and Fallopian tube with the use of a radiographic contrast medium
      [1]. This method is an integral part of gynaecological examination and its value
      has not been underestimated in the modern gynaecological practice. GOAL OF THE
      STUDY: The goal of the study was to evaluate the reliability of HSG in the
      diagnosis of Fallopian tube and to compare the obtained results with laparoscopic
      findings. METHODS: The study included 140 infertile women. HSG was performed in
      the first half of the cycle, usually on the ninth day, without anaesthesia. The
      instruments after Schultze were used; 15 mL of Telebrix-contrast was used. Three
      radiograms were done. Laparoscopic examination was carried out in general
      endotracheal anaesthesia. A Storz laparoscope was used. CO2 was used for
      artificial pneumoperitoneum and indigolipstick for tube passage. The obtained
      findings were elaborated statistically. Descriptive and analytic models were
      used. p < 0.05 and p < 0.01 were considered as a risk factor of statistical
      significance. RESULTS: An approximate time interval between the two procedures
      was 5.18 months. Normal findings of HSG examination were noted in 53 women
      (37.9%); tube occlusion in 67 women (47.9%), and peritubal adhesion with tubal
      passage in 20 (14.3%) patients. A normal finding was found in 56 women (40.0%),
      tubal occlusion in 64 women (45.7%), and peritubal adhesion with tubal passage in
      20 (14.3%) patients. HSG and laparoscopic findings regarding normal tubes were in
      agreement in 32 women (22.9%), tubal occlusion in 35 women (25.0%) and peritabal
      adhesion with tubal passage in 5 (3.6%) patients. The best sensitivity of HSG was
      observed in detection of proximal tubal occlusion (78%), and the smallest in
      occlusion with the accompanying adhesion (2%). The best specificity of HSG was
      noted in the diagnosis of combined occlusions (96%) and the smallest in tubal
      passage with peritubal adhesion (25%). There were 15% of false negative findings
      and 17.1% of false positive findings. DISCUSSION: The time interval from one to
      the other procedure can be considered as an important factor in laparoscopic
      confirmation or negative HSG findings. With the continuation of the time interval
      the conditions are made for the aggravation of old and occurrence of new
      pathological processes in genital internal female organs. The possible causes of
      differential diagnosis of tubal occlusion between HSG and laparoscopic
      examination might be: 1) unequal anaesthesia during HSG and laparoscopic
      examination; 2) different properties of contrast media; 3) anatomic variations in
      the width of lumen tubes; 4) erroneous interpretation of the results. The
      sensitivity of HSG in this study was different in various types of tubal passage.
      In other studies the sensitivity of HSG was from 65% [10] to 96%[7]. The high
      specificity was found during detection of combined tubal occlusion (96%). The
      results of other authors were similar [7, 10]. This is a good contribution to the
      statement that HSG is a useful test of tubal obstruction. A rather high percent
      of false positive results of HSG was established in this study. The possible
      reasons might be tubal spasm and endometrial polyp in the area of the uterine
      opening of the tubes. CONCLUSION: On the basis of the obtained results, the
      following conclusions can be drawn: 1) HSG is a simple method for examination of
      female sterility; 2) HSG and laparoscopy are the complementary methods in the
      examination of tubal sterility; 3) HSG is inferior in relation to laparoscopy in
      the examination of peritubal adhesion.

PMID- 11534280
TI  - [Palliative care in patients with malignant diseases].

PMID- 11534281
TI  - [Systemic therapy in carcinoma of the renal parenchyma].

PMID- 11534282
TI  - [Topographic distribution of multiple sclerosis in the Belgrade municipalities].
AB  - The frequency of multiple sclerosis (MS) varies greatly in different parts of the
      world, but also within some countries. Many epidemiological surveys of
      geographical pattern of MS identified areas of different risk of MS in relation
      to the latitude. The study of disease clusters is a potentially powerful strategy
      in revealing the aetiology of a disease. A series of space and time clusters of
      MS has been described over the years, especially in islands' populations. The
      Belgrade region is located on 628 m height above the sea level, between latitudes
      44 and 45 degrees north of the equator, and longitudes 20 and 21 degrees east of
      the Greenwich. The district of Belgrade is divided into 16 municipalities and
      extends over an area of 3,222 km2. According to the 1991 census, the area has a
      population of 1,602,226 inhabitants. All persons who were affected and/or died
      from MS with residence in Belgrade region had been registered from January 1,1985
      to December 31,1996, on the basis of a retrospective analysis of hospital
      records. The main sources for this study were hospital case records in all 4
      neurological hospitals in Belgrade (Institute of Neurology of the Serbian
      Clinical Centre, which is the primary referral national centre for
      suspected/diagnosed MS patients in Serbia, and three Departments of Neurology
      which belong to Zvezdara Clinical Centre, Dr. Dragisha Mishovitsh Clinical
      Centre, and Military Medical Academy). Only clearly diagnosed and fully
      documented cases with clinically and laboratory supported MS according to Poser's
      criteria were included. For each patient, two neurologists (JD and NS) and one
      epidemiologist (TP) reviewed all data collected in order to verify the validity
      of the diagnosis. The prevalence, as a number of persons with MS in the
      population at risk, was calculated on December 31, 1996, for each municipality
      and for the Belgrade population as a whole. The Belgrade municipalities were
      categorized according to MS prevalence level, as category 1 (> or = 50/100,000)-
      Stari Grad, Vrachar, Vozhdovac, Rakovica, Barajevo, Zvezdara; category 2 (30
      49/100,000)--Savski Venac, Novi Beograd, Chukarica, Zemun; and category 3 (<
      30/100,000)--Palilula, Sopot, Grocka, Obrenovac, Lazarevac and Mladenovac. The
      geographic distribution was estimated according to the prevalence of MS, and
      hypothetical cluster of the disease was tested by chi-square test. On December
      31, 1996, the prevalence of MS in the Belgrade population was 44.87/100,000. The
      highest MS prevalence was registered in the municipality of Vrachar
      (74.63/100,000), and the lowest in the municipality of Mladenovac (17.73/100,000)
      (Table 1). Municipalities which are grouped within the 3 categories are not
      statistically significantly clustered (chi-square = 1.479, p > 0.05).

PMID- 11534283
TI  - [Analysis of programmed pacing rate levels in patients with the carotid sinus
      hypersensitivity syndrome and implanted Clarity pacemakers].
AB  - New Clarity DDDR pacemaker system (Vitatron Medical B.V.) Clarity DDDR, provides
      an option for recognizing sudden rate drop and responding by intervention pacing
      until it detects the recovering. In patients in whom syncopal episodes are mainly
      caused by occasional drops in heart rate, Sudden Rate Drop Intervention feature
      intends to provide high rate intervention pacing. We have implanted 10 of these
      devices in our Centre, 2 of which in patients with hypersensitive carotid sinus
      syndrome. In patients with carotid sinus syndrome it is possible to provoke this
      situation by sinus caroticus massage. In both patients, we activated Sudden Rate
      Drop Intervention on DDD mode pacing and used protocol for testing the necessary
      level of sudden Rate Drop Intervention Rate. Both patients gave their informed
      consent to be submitted to this testing. Pacemaker software assumes rate
      intervention level of 110 bpm. We tested our patients for rate levels of 90 and
      110 bpm. Massaging the carotid sinus during 5 seconds, we provoked sudden Rate
      Drop Intervention 10 times, in each patient, 5 times at intervention rate of 90
      and 5 times at 110 bpm. Patients were unaware of the programmed intervention rate
      and were merely expected to report any different sensations experienced during
      the testing. In all 20 tests, pacemaker responded to sudden rate drop elicited by
      carotid sinus massage (100%), that was verified by selected event recordings.
      After the massage, no patient experienced any sensation at sudden rate drop
      intervention rate level of 90 bpm in a total od 10 tests (100%), while 8 of 10
      messages at 110 bpm intervention rate provoked palpitations (80%). We concluded
      that lowering of Sudden Rate Drop Intervention Rate Level from 110 BPM to 90 BPM
      did not affect the reliability of system reaction, but changes of patient's
      awareness of heart beats. As a final conclusion, it should be said that basic
      prerogatives of a pacing system are: safety and efficacy with minimal energy
      consumption, and in this case, quality of life option that a patient practically
      does not feel intervention when it occurs, are all met.

PMID- 11534284
TI  - [A diagnostic device for determination of the volumetric outline of a model of
      the maxillodental system].
AB  - To obtain a more accurate volumetric outline of a diagnostic jaw model with
      outline translated to the plain system (paper) and subsequent construction of a
      plot analytical model, the author proposes the universal device--a
      gnathooclusiograph, that measures and simultaneously fixes the points and lines
      of the model's relief outline on three planes. The obtained coordinates and
      graphical images are transferred to the computer complex that allows three
      dimensional measurements in the system of the coordinates X, Y, and Z.

PMID- 11534285
TI  - [X-ray tubes with ionic indemnification of negative space electronic charge].
AB  - How to increase anode current in the fine-focus diagnostic X-ray tubes (XTs) is
      analyzed. It has been found that there are new three-class XTs that have
      advantages of both ionic and electronic tubes. The specific feature of the new
      class XTs is the gaseous atmosphere available in the working volume. Ionizing the
      gaseous atmosphere with a emission electron flow in the path from the cathode to
      the anode yields a dot volumetric positively charged ion grid that closely
      approaches the cathode and can pay a big bonus in anode current output.

PMID- 11534286
TI  - [Method of calculating the equivalent tumor dose as a function as to irradiated
      tumor tissue volume].
AB  - Based on the assumption that tumor tissue consists of normal and radiation
      resistant, that the survival of both types of tumor cells may be described by LQ
      functions and that the count of radiation-resistant cells is in proportion to
      that of tumor cells, the author has developed a method for calculating the
      equivalent tumor dose as a function as to irradiated tumor tissue volume for the
      fixed value of a single dose in the session of radiation. The developed formalism
      may be used to test the hypothesis that the count of clonogenic and radiation
      resistant cells is in proportion to the baseline number of the cells in the tumor
      tissue.

PMID- 11534287
TI  - [Modeling of the structure of hemodialysis apparatuses].
AB  - By taking into account the general principles in the design of extrarenal blood
      clearance apparatuses, all existing hemodialysis apparatuses (HDAs) are
      classified by the transportation of the controlling medium, by the degree of
      automation, by the control of amounts of the liquid removed from the patient, and
      by their connection to the latter. The proposed classification of HDAs and a
      model of the structure of dialysate units showed the unity of principles in
      designing HDAs irrespective of the specific features of their design, which may
      be used to ensure the versatility, reproducibility, technological effectiveness,
      convenience in application, and efficiency of the apparatuses designed.

PMID- 11534288
TI  - [Visualization of data from statistical analysis of the parameters of
      somatosensory evoked potential components].
AB  - A method is proposed to construct bar charts of statistical differences in the
      parameters of somatosensory evoked potentials, which simultaneously reflect the
      level of sensitization and reactivity of pathological excitation generators
      forming in the central nervous system in chronic pain syndromes. This approach
      can promote visualization and objectification of functional disorders of the
      central nervous system during treatment. Moreover, there may be prognosis of a
      degree of chronization of the pain syndrome.

PMID- 11534289
TI  - [Methods of synthesizing the index of an operator's psychophysiological stress].
AB  - The paper presents a procedure for synthesizing the psychophysiological stress
      that may be used to solve a wide range of problems associated with the control of
      an operator's professional skills in relation to his/her individual response to
      working conditions, nature, and results of activities.

PMID- 11534290
TI  - [Spectral distribution of braking radiation in the tungsten anode X-ray tubes].
AB  - An analytical expression (mathematical model) of the spectral distribution of
      braking radiation in the in tungsten anode X-ray tubes has been derived. The
      discrepancy of the calculated spectra with experimental findings is no more than
      +/- 6%.

PMID- 11534291
TI  - [Metrological software of laser medical equipment].
AB  - The paper considers the laser medical equipment situation that has established in
      Russia and that is characterized by the wide medical application of laser
      technologies and appropriate software and by inadequate development and
      imperfection of required metrological software and maintenance of laser
      equipment.

PMID- 11534292
TI  - [Results of testing a non-protrusion hip joint prosthesis].
AB  - To prevent protrusion of the socket of an endoprosthesis into the pelvis, an
      experimental nonprotrusion endoprosthesis has been designed and tested. The
      endoprosthesis is of novel design; however, its production is rather simple. The
      efficiency of its use is strongly evidenced by reasonably long-term experiments.
      Comparing the results of use of a routine design endoprosthesis versus the
      nonprotrusion one under the same loading conditions has shown that the novel
      endoprosthesis is better.

PMID- 11534293
TI  - [Experimental study of the relationship of the level of blood hemolysis and the
      design of artificial heart valves].
AB  - The paper deals with experimental studies into the level of hemolysis that
      accompanies the performance of artificial cardiac valves (ACV). The studies were
      conducted by two ways. The first study determined the level of hemolysis when
      artificial cardiac valves worked and donor blood performed. The second one was
      that a polymer was added to the model physiological fluid, the degree of
      hemolysis was determined by the changes occurring in the time of relaxation of
      elastic stress in the model fluid samples taken during tests. The experiments
      showed polyethylene oxide break-down to be the most accurately modelling process
      of hemolysis.

PMID- 11534294
TI  - [Equipment and technology for taking digital X-ray fluorographic films].
AB  - The paper deals with X-ray photogrammetry. It presents designs of different types
      of currently available digital X-ray fluographic apparatuses, their technical
      data and operating characteristics. Whether these apparatuses can be used for
      stereo X-ray photogrammetric survey is assessed.

PMID- 11534295
TI  - [Definition of quantum efficiency of X-ray detectors].
AB  - Different definitions available in the literature on the quantum efficiency of X
      ray detectors are presented and compared. The relationship of this parameter to
      spatial frequencies for quantum accounting receivers and energy accumulating ones
      is analyzed. A procedure is proposed for evaluating the quantum efficiency of the
      detectors in the area of zero spatial frequencies, which is rather simple and
      requires no special testing equipment.

PMID- 11534297
TI  - Fetal ethology and its relevance to perinatal medicine.
AB  - Fetal ethology means fetal activity and behavioral states in the uterine
      environment. Behavioral states may be defined by various measurable physiological
      variables, such as heart and respiratory rates, eye movements, body tone and body
      movements. Fetal motor behavior provides information about the early stages of
      the neurodevelopmental process. Movement was the first aspect of fetal behavior,
      the clinical significance of which became was recognized. Fetal behavior provides
      an opportunity for studying motor, sensory and cognitive functions in the fetus.
      Behavior can be utilized to study the immediate well-being of the fetus. The
      latter can be compromised as a result of a number of pathological factors. In
      high risk pregnancies, the study of fetal behavior may help the clinician to
      establish the optimum time for the delivery.

PMID- 11534296
TI  - [Shoulder dystocia--consequences and procedures].
AB  - Shoulder dystocia is defined as a standstill of delivery after the birth of the
      head and is attributed to an insufficient rotation of the shoulder. Risk factors
      include a history of prior macrosomia or shoulder dystocia, maternal obesity or
      excessive weight gain during pregnancy, maternal diabetes or postdate pregnancy
      and prolonged descent or midpelvic operative delivery. Neonatal morbidities
      associated with traumatic birth include fetal hypoxia with acidosis and permanent
      brachial plexus injury. THERAPY: After the recognition of a shoulder dystocia a
      series of steps should be undertaken beginning with cutting or extending the
      episiotomy, McRobert's Manoeuvre, Wood's Manoeuvre and delivery of posterior arm.
      A tocolytic administered as a bolus or general anesthesia also may be needed.
      Documentation should include the exact time the dystocia was recognized by the
      midwife and/or obstetrician, the time at which intervention was started and a
      detailed operative report.

PMID- 11534298
TI  - [Typical forms of choriocarcinoma in clinical practice--diagnosis and therapeutic
      course in four patients].
AB  - The paper reports on four patients with choriocarcinoma. In two of them, the
      choriocarcinoma was found after abortion, in one of them following termination of
      pregnancy, and in the last patient a hydatidiform mole was present. In all
      patients increased beta-HCG was found. One patient had lung metastasis at the
      time of diagnosis. In another patient, choriocarcinoma was suspected owing to
      ultrasonographic vaginal examination. According to the Bagshawe Score, 3 patients
      were low-risk and were subjected to methotrexate. One patient was medium-risk and
      received PEB chemotherapy. All four patients are regarded as cured.

PMID- 11534299
TI  - [Reasons for the change in HRT therapy from the perspective of women. Results of
      the German Cohort Study on Women's Health].
AB  - Acceptance and reasons for changing the HRT play an important role against the
      background of the efficiency of the therapy and increasing life expectancy. Women
      in developed, industrialized countries live about one-third of their lives in the
      peri- and postmenopausal phases.--The frequency of switching and the reasons were
      examined in an interim analysis of the German cohort study on women's health.
      This historical analysis was based on over 10,000 women (i.e. about 300,000 man
      years of observation), of whom 2,002 women (aged 40-65) were constant users of
      HRT.--The prevalence of use and the frequency of switching to other HRT
      preparations were somewhat higher in women above 60 as compared to those aged 40
      59. The duration of use had no impact on the prevalence of use or the frequency
      of switching or cessation. Neither education nor the past use of oral
      contraceptives showed a clear association with the frequency of switching. The
      most frequent reasons for switching or cessation were adverse events, i.e.
      reasons independent of age. Women aged from 40 to 49 more frequently reported
      weight gains, menstrual disturbances, headaches, and impaired well-being than did
      older women. A recurrence of menstruation was more frequently reported by women
      over 60 as the reason for switching or discontinuing HRT.--The knowledge of the
      reasons for women switching or discontinuing HRT underlines the importance of
      close collaboration between women and their gynaecologists, as well as that of
      intensified research for optimal products.

PMID- 11534300
TI  - [Oncoplastic techniques for immediate reconstruction with nipple-areolar
      preservation following radical resection of a centrally located breast cancer].
AB  - There are few breast-conserving therapies (BCT) for centrally located breast
      cancer. The present paper describes a BCT for breast cancers in such a location,
      which permits conservation of the nipple-areola complex (NAC), provided this has
      not been infiltrated. After histological detection of the breast cancer by punch
      biopsy, a central segmental mastectomy and an axillary dissection are performed.
      An immediate reconstruction of the subareolar defect is carried out by means of a
      local flap technique, thus conserving the NAC.

PMID- 11534301
TI  - [Optimization of the indications for breast biopsy by preoperative conference].
AB  - In connection with a series of second reviews of mammographies as part of a
      preoperative conference, criteria are presented that allow a correct diagnosis,
      thus avoiding unnecessary breast surgery. In addition, it is shown that
      preoperatively all diagnostic findings must be reviewed as a whole, in order to
      make the appropriate decision for the patient. A total of 145 patients was
      admitted for breast surgery between 1994 and 1997. Group 1: The mammographies of
      133 patients were re-evaluated and additional exams were performed. In only 17%
      (23 cases) could the first diagnosis be confirmed and the patients went to
      surgery. In 110 cases a single mammographic view sufficed to show that there was
      no suspicious finding in the breast. Instead there was a pseudolesion, not
      visible after an image had been taken with appropriate technique. Group 2: For 12
      additional patients, a synopsis of different findings was presented and analysed
      at a preoperative conference. Even although imaging may have been performed
      correctly, a conference can still contribute to the optimization of indocations.
      Unnecessary breast surgery can can thus be avoided.

PMID- 11534302
TI  - Modified fetal biophysical profile in the assessment of perinatal outcome.
AB  - The aim of the study is the evaluation of variables of the biophysical profile in
      the assessment of perinatal outcome. The prospective study included 87 pregnant
      women with singleton pregnancy in the 28th to 42nd week of gestation with
      clinically and ultrasonically verified fetal growth retardation, where the fetal
      biophysical profile was assessed antenatally. Through the factor analysis of
      biophysical profile variables we obtained values indicating the contribution of
      individual variables to the predictability of perinatal outcome. 70% of the
      patients were examined in 15 minutes according to the principles of modified
      biophysical profile. The most sensitive variable of the biophysical profile in
      the prediction of perinatal outcome was the amniotic fluid volume, followed by
      fetal breathing movements, non-stress test and fetal movements, while the lowest
      prediction value was assigned to the fetal tone. The modified biophysical
      profiles need to be perfected on a larger number of pregnant women, which would
      advance the predictability of this method in detection of hypoxically endangered
      fetuses.

PMID- 11534304
TI  - [Hormone replacement therapy--a risk-benefit analysis].

PMID- 11534303
TI  - Treatment of a retained placenta with intraumbilical oxytocin injection.
AB  - The aim of the study was to assess the effect of intraumbilical administration of
      oxytocin in the management of retained placenta. This prospective double-blinded
      clinical study included 31 mothers with retained placenta. The women were divided
      into three groups: group 1 (n = 19) was given 20 IU syntocinon in 20 ml 0.9% NaCl
      saline intraumbilically into the vein (IUV); group 2 (n = 8) received 20 ml 0.9%
      NaCl saline; and group 3 (n = 4) received 0.2 mg ergometrine IUV in 20 ml 0.9%
      NaCl saline. Intraumbilical injection was used 30-45 min after delivery, and the
      distal cord segment was clamped to the umbilical vein.--In group 1, placental
      expulsion within 60 min of IUV oxytocin injection occurred in 13 (68.4%) women;
      in group 2, placental expulsion was recorded in one (12.5%) woman, whereas no
      placental expulsion occurred in group 3 women (p < 0.001). Complications in terms
      of major hemorrhage were not observed in group 1, whereas a hemorrhage of > 500
      ml was recorded in one group 2 and 3 woman each. Febrility developed in one
      woman, and abdominal pain in two women from each group. Manual lysis of the
      placenta was performed in seven group 1, seven group 2, and all four group 3
      women. IUV oxytocin injection provides a useful and inexpensive non-surgical, non
      aggressive, cheap and pharmacological method which should be included in the
      treatment protocol for retained placenta before turning to the procedure of
      manual lysis of the placenta.

PMID- 11534305
TI  - Critical appraisal of published research evidence: treatment of gestational
      diabetes.

PMID- 11534306
TI  - A case for lipid lowering? Response to Dr Paul Durrington.

PMID- 11534307
TI  - A comparison of glyburide and insulin in women with gestational diabetes
      mellitus.

PMID- 11534308
TI  - When communication has gone wrong between a doctor and a patient.

PMID- 11534309
TI  - Belgian standards for patient safety in anesthesia. The Belgian Anesthesia
      Patient Safety Steering-Committee.

PMID- 11534310
TI  - Use of remifentanil in combination with desflurane or propofol for ambulatory
      oral surgery.
AB  - We evaluated the use of remifentanil administered as a component of an inhalation
      or of a Target Controlled Infusion (TCI) anesthetic technique during outpatient
      oral surgery. Sixty-three unpremedicated patients undergoing removal of four
      impacted third molars participated to this prospective, randomized study.
      Anesthesia was induced with Propofol and Rocuronium. Remifentanil 1 microgram.kg
      1 i.v. was given over 30 s followed by a continuous infusion reduced from 25%
      each time a tooth was removed (0.25-->0.0625 microgram.kg-1 min-1). Anesthesia
      was maintained with Desflurane (group D, n = 31) (end-tidal concentration 4-6%)
      or Propofol (group P, n = 32) (initial infusion TCI 8 micrograms.ml-1 reduced to
      2-3 micrograms.ml-1 after intubation). Corticosteroids, a non-steroidal anti
      inflammatory drug (NSAID) (Diclofenac) and a partial mu agonist drug (Tramadol)
      were administered i.v. during the procedure to prevent early postoperative pain.
      Recovery time, postoperative pain, recovery of cognition and nausea or vomiting
      were also evaluated during the first six postoperative hours. Overall mean
      systolic blood pressures and heart rate were similar in the two groups during
      surgery. Mean times to extubation and to recall of birth-date and room number
      were also similar. The quality of awakening was good in the two groups. Most
      patients complained of moderate pain or had no pain during the first six
      postoperative hours. The incidence of nausea and vomiting was similar in both
      groups. No other side effect was observed. These data suggest that the
      association of Remifentanil, Methylprednisolone, Diclofenac and Tramadol is an
      useful technique in ambulatory oral surgery in two comparable anesthetic
      regimens.

PMID- 11534311
TI  - Pediatric anesthesia and sedation in remote locations.

PMID- 11534312
TI  - Comparison between the cuffed oropharyngeal airway and the laryngeal mask with
      respect to breathing pattern and capnography.
AB  - This study evaluates spontaneous breathing and CO2-monitoring under sevoflurane
      anesthesia with a cuffed oropharyngeal (COPA) or laryngeal mask (LMA) as airway.
      Forty patients (ASA I-II) scheduled for varicose vein surgery were given 2 mg.kg
      1 propofol for insertion of a COPA or a LMA. Anesthesia was maintained with
      sevoflurane at 2.5 vol% in 40/60% O2/N2O, while the patients breathed
      spontaneously. Arterial and end-tidal CO2 partial pressures (PaCO2, PE'CO2),
      respiratory rate (RR), tidal volume (VT) and expired minute volume (EMV) were
      recorded at different times before and during the procedure. The dead space (VD)
      was calculated from the modified Bohr equation. The PaCO2 and the PE'CO2 were
      generally lower in the LMA group as compared to the COPA group during most of the
      procedure. EMV was also higher in the LMA group as compared to the COPA group.
      This difference becomes statistically significant 5 min. before the end of
      surgery (6.22 +/- 0.34 vs. 5.23 +/- 0.39 L.min-1). RR was consistently higher in
      the LMA group, while VT and VD were similar. Correlation of PE'CO2 and PaCO2 was
      0.87 when measured in the COPA group and 0.88 in the LMA group. The prediction of
      PaCO2 by PE'CO2 was more sensitive in the LMA group as compared to the COPA
      group. We conclude that spontaneous breathing is better with the LMA.

PMID- 11534313
TI  - Feedback controlled anesthesia: can the computer replace the anesthesiologist?

PMID- 11534314
TI  - Target controlled infusion of remifentanil and propofol for cesarean section in a
      patient with multivalvular disease and severe pulmonary hypertension.
AB  - A 36 year old parturient with known valvular heart disease was admitted with
      respiratory distress and fatigue after 35 weeks of pregnancy. Echocardiography
      revealed severe tricuspid regurgitation, mitral stenosis and aortic valve
      insufficiency. Following clinical examination and insertion of a radial and
      pulmonary artery catheter it was decided to perform a Caesarean Section. The
      pulmonary artery pressure upon arrival in the operating theatre was 105/50 mm Hg
      whereas cardiac output was 3.5 l/min. Induction of anesthesia was performed with
      a target controlled infusion of remifentanil and propofol combined with
      rocuronium bromide. Haemodynamic variables remained very stable during and after
      intubation. The lungs of the apnoeic baby were manually ventilated until
      spontaneous respiration began at 1 minute post delivery. Apgar scores were 3, 7
      and 9 after 1, 5 and 10 minutes respectively. Umbilical artery pH was 7.29. The
      patient's haemodynamic status gradually improved over the following few days. Two
      months following delivery she underwent unevenful valvular surgery.

PMID- 11534315
TI  - [What is your diagnosis? Myopericarditis].

PMID- 11534316
TI  - [Visual diagnoses in pediatrics. Xanthomas].

PMID- 11534317
TI  - [Low molecular weight heparin (dalteparin) in treatment of patients with
      thromboembolism incidents].
AB  - Low molecular weight heparine (LMWH) is an established treatment for deep venous
      thrombosis during the initial phase of the illness as well as for prophylaxis of
      thrombosis. There are only few studies concerning the use of LMWH in the initial
      treatment of lung embolism. 138 Patients with either deep venous thrombosis at
      least reaching the vena poplitea and/or lung embolism have been randomised into
      two groups. One group was treated with unfragmented heparin. The second group
      received a single dose of 200 I.E./kg body weight/d LMWH (Dalteparin). The
      results were compared with regard to the recurrence of thrombosis and embolism,
      bleeding, heparin-induced thrombopenia and mortality. RESULTS: A total of 138
      patients were randomised. 13 patients were excluded later. The two groups were
      comparable regarding age, sex, weight and diagnosis. The average treatment lasted
      8.3 (5-26) days in the LMWH-group and 7.4 (4-14) days in the heparine-group. The
      average hospital stay was 10.4 days in the LMWH-group, and 11.0 days in the
      heparine-group. The complication rate was 5 (3.1%) (5 events: 3 hemorrhages, 1
      reembolism, 1 death) in the LMWH-group and 4 (2.5%) (4 events: 3 bleedings, 1
      sepsis of the venous catheter) in the heparine-group. We found no significant
      outcome difference between the two treatment groups. CONCLUSION: Weight-adapted
      (200 IE/kg/day) subcutaneous application of Dalteparin once daily in the
      treatment of patients with deep venous thrombosis or lung embolism is as safe as
      intravenous treatment with unfragmented heparine.

PMID- 11534318
TI  - [Clinical effectiveness and tolerance of climbazole containing dandruff shampoo
      in patients with seborrheic scalp eczema].
AB  - Pityrosporum ovale appears to play an important role in the pathogenesis of
      dandruff as a symptom of seborrheic dermatitis. Climbazole is an antimycotic
      agent with a high in vitro and in vivo efficacy against P. ovale. In the
      presented work we investigated the efficacy and safety of a climbazole 0.65%
      shampoo on seborrheic dermatitis of 30 volunteers. Subjects were diagnosed as
      having moderate to severe seborrheic dermatitis of the scalp. After a 1-week
      washout and a 4-week treatment the clinical evaluation showed a successful
      reduction of dandruff, skin redness and itching in 80% of the volunteers and a
      mild improvement in 20% of the volunteers. The cosmetic acceptability was very
      good by the majority. It is concluded that the formulation tested is effective in
      the treatment of moderate to severe dandruff.

PMID- 11534319
TI  - [Therapy of myasthenia gravis].
AB  - The treatment of myasthenia gravis is a difficult entity. We especially discuss
      the immunosuppressive treatment with regard to the literature. In patients with
      thymoma all authors agree in thymectomy. In generalized myasthenia, even without
      thymoma, thymectomy should be performed in "younger" patients. In "elderly"
      patients thymectomy as treatment of choice is controversial. The basis of
      immunsuppressive therapy are corticosteroids, additionally azathioprine can be
      given considering the delay in response and the major side effects. As today,
      cyclophosphamide and cyclosporine A are too toxic for routine use, except third
      choice in therapy resistant patients as ultima ratio. The procedure of choice in
      myasthenic crisis is plasma exchange if the patient tolerates it. Alternatively
      intravenous immunoglobulin should be given. In pure ocular myasthenia treatment
      is controversial in the literature. In the last few years there is a tendency to
      treat this form early like generalized myasthenia, especially in young patients,
      to prevent generalization.

PMID- 11534320
TI  - [Pneumomediastinum after cocaine administration].

PMID- 11534321
TI  - [When should antiretroviral therapy be started?].

PMID- 11534322
TI  - Comparative anatomy of the male guinea-pig and human lower urinary tract:
      histomorphology and three-dimensional reconstruction.
AB  - The guinea-pig is often used for experimental studies in urology. However, the
      anatomy of the lower urinary tract of the guinea-pig is poorly described in the
      literature. The structure and function of the lower urinary tract, i.e.
      continence, micturition and sexual function, are closely related to the gross
      anatomy of the pelvis and the fine structure of the musculature. We investigated
      the anatomy and histomorphology of the lower urinary tract by serial sections in
      male guinea-pigs and compared it to that in humans. Immunohistochemical stainings
      for alpha-smooth muscle cell actin were used to differentiate between smooth and
      striated muscles. By using whole pelvic preparations, including all internal
      organs preserved in their in situ location for three-dimensional reconstruction,
      we developed three-dimensional models, which elucidate the spatial relationship
      of all muscular structures and can help to deduce functional aspects of lower
      urinary tract function. In the guinea-pig, most of the muscles found in humans
      can be demonstrated in comparable location and extension. However, the structure
      of the prostate and the existence of the so-called coagulation glands define a
      significant difference in the morphology of the prostatic urethra.

PMID- 11534323
TI  - Neurotrophin receptor-like proteins in the bovine (Bos taurus) lymphoid organs,
      with special reference to thymus and spleen.
AB  - Increasing evidence suggests that neurotrophins could regulate immune functions
      acting directly or indirectly on immunocompetent cells. The indirect pathway
      involves stromal cells of the primary and secondary lymphoid organs. In the
      present study the occurrence of Trk proteins (TrkA, TrkB and TrkC), regarded as
      the high-affinity signal-transducing receptors for neurotrophins, was
      investigated in cow lymphoid organs using immunohistochemistry. The thymus and
      spleen of both fetal and adult animals, and the palatine tonsils, lymph nodes and
      Peyer's patches of adult animals, were analysed. Unidentified cells displaying
      TrkA-like immunoreactivity were found in the fetal thymus, whereas those
      expressing this protein in the adult gland were identified as epithelial cells.
      In the spleen, immunoreactive TrkA was observed in cells of the white pulp. TrkB
      immunoreactivity in both fetal and adult thymus and spleen was localized in
      monocyte/macrophage cells. As a rule, TrkC was absent from the thymus and the
      spleen independent of the animal's age. Different types of stromal cells, but
      never the lymphocytes themselves, displayed TrkA, TrkB, or TrkC immunoreactivity
      in the other lymphoid organs analysed. As in other vertebrate species, Trk
      proteins in the lymphoid organs of the cow were localized in the stromal, non
      lymphoid cells, thus suggesting that neurotrophins might regulate the immune
      function acting indirectly on lymphocytes.

PMID- 11534324
TI  - The parotid, mandibular and lateral retropharyngeal lymph nodes of the camel
      (Camelus dromedarius).
AB  - The parotid, mandibular and lateral retropharyngeal lymph nodes of the dromedary
      camel were examined using both light and electron microscopy. All three lymph
      nodes were lobulated. They did not show the characteristic medulla, cortex and
      paracortex of typical lymph nodes. Instead, they contained lymphatic nodules,
      dense anodular lymphoid tissue and diffuse lymphoid tissue dispersed throughout
      the lymph node. Networks of sinuses were present in the diffuse lymphoid tissue.
      The diffuse lymphoid tissue in the periphery of all lymph nodes examined was
      characterized by numerous erythrocytes within and around its network of sinuses.
      The nodal sinuses were contiguous with the septal vessels, which are considered
      the possible source of erythrocytes seen in this study. The lymph nodes that were
      seen in this study resembled the haemolymph nodes of other mammals with regard to
      their content of erythrocytes but were unique in being located in sites that were
      typical of ordinary lymph nodes. Morphometric analysis has shown that the
      percentage volume densities of the stroma and the various parenchymal components
      were similar in the three lymph nodes.

PMID- 11534325
TI  - Study of lobation and vascularization of the lungs of wild boar (Sus scrofa).
AB  - The purpose of this study was to describe the anatomy of the lungs of wild boars
      for comparison with those of domestic swine. It was found that the right lung of
      the wild boar is divided into four lobes: cranial, median, caudal and accessory,
      whereas the left lung is divided into two lobes: cranial and caudal. In 93.4% of
      the cases, right pulmonary artery separates into the ascendant, descendant,
      median, accessory and caudal branches. In 73.3% of the cases, left pulmonary
      artery separates most frequently to form three branches to the cranial lobe,
      whereas the median lobe is generally supplied by only one arterial branch. There
      is a single pattern of bronchial distribution: in the right lung a tracheal
      bronchus leads to the cranial lobe, where it separates into the cranial and
      caudal bronchi and there are also bronchi to the median, caudal and accessory
      lobes. In the left lung, the large bronchus separates to form two branches, one
      of which further separates to form two branches to the cranial lobe whereas the
      other forms a single branch to the caudal lobe.

PMID- 11534326
TI  - On the development of the papillary body in the feline claw.
AB  - The pre- and post-natal development of the feline claw was studied in 22 feline
      fetuses with a crown-rump length (CRL) ranging from 40 to 160 mm, in six kittens
      up to an age of 22 days, and in four adult cats. In fetuses up to a CRL of 75 mm,
      the characteristic shape of the feline claw was developed. Segment-specific
      dermal modifications in the various segments, especially the dorsal ridge,
      started to develop in fetuses with a CRL between 75 and 105 mm. Modifications of
      the papillary body in the different claw segments took place in the last third of
      prenatal development and were continued postnatally. At first, the basal lamina
      became wavy, followed by the formation of small dermal microridges, which would
      be enlarged to dermal ridges and lamellae. In the claw of adult cats, the
      papillary body was very small. The dermal tissue of the proximal part of the
      coronet formed low microridges with short papillae originating on and between
      these low ridges. In the wall segment, dermal microridges were formed which were
      arranged in a parallel fashion, and in the distal part of the wall, short dermal
      micropapillae arose on the crest of each microridge. In the sole segment, thin
      dermal lamellae were developed. The sequence of papillary body development and
      the varying conformations of the papillary body in the different segments of the
      feline claw are compared to those in the nail, the canine claw and hooves.

PMID- 11534327
TI  - Identification of positive cells to interleukin-4 in bovine haemal nodes.
AB  - The bovine haemal nodes are lymphatic organs located in the haemal circulation.
      Their parenchyma is represented by plasma cells, macrophages and B and T
      lymphocytes. The T helper type 2 (Th2) CD4 lymphocyte can be found within the T
      lymphocytes. The activated Th2 CD4 lymphocyte produces interleukin-4 (IL-4), a
      peptidic hormone involved in the acute-phase immune response. This interleukin
      can promote either B-lymphocyte differentiation and T-lymphocyte proliferation or
      it can promote the type of immunoglobulin that can be liberated. Our results have
      shown, by immunostaining with anti-IL-4, not only the presence and localization
      of these lymphocytes in bovine haemal nodes but also the participation of
      polymorphonuclear cells (neutrophils) in the storage of IL-4. These results give
      value to the humoral and cellular immunological importance of haemal nodes in
      bovines and they can serve as a contribution to determine the cross-reactivity of
      bovine IL-4 with the human anti-serum used in this work.

PMID- 11534328
TI  - Demonstration of the nerve distribution of the masticatory muscles in rabbits
      (Oryctolagus cuniculus).
AB  - Two methods can be used in order to demonstrate the nerve distribution of an
      organ. One is the three-dimensional reconstruction of the innervation pattern of
      the organ by tracing images of that organ from serial histological sections. The
      other is the in toto staining of the organ with subsequent clearing of the
      muscles. In the present study, in order to visualize the nerve distribution of
      the organ, that organ was completely cleared and the nerve fibres were stained.
      Detailed morphological structure of the intramuscular nerve distribution of a
      certain region and its functions are of importance not only for anatomists and
      physiologists but also for clinicians. In this study eight New Zealand rabbits
      were used to visualize the intramuscular nerve distribution of the muscles
      involved in mastication (temporalis m., pterygoideus medialis m., digastricus m.,
      retractor mandibulae m. and masseter m.). The main nerve bundle was observed
      entering into the muscle as a single trunk and dividing into three branches in
      the muscle. These branches were also observed dividing into several subbranches
      while going to the periphery. When the samples were examined under a
      stereomicroscope, 'Y'-, 'I'- and 'O'-shaped communications between those branches
      were observed.

PMID- 11534329
TI  - Immunohistochemical study of the ontogeny of prochymosin--and pepsinogen
      producing cells in the abomasum of sheep.
AB  - The appearance and development of prochymosin- and pepsinogen-producing cells
      were investigated in the ovine abomasum from fetus to adult using
      immunohistochemistry. Prochymosin immunoreactivity appeared first in the proper
      gastric glands of the 100-day-old fetus. The intensity and distribution of
      prochymosin-immunoreactive cells increased gradually with the progress of
      gestation, and their most intense immunoreactivities and widest distribution were
      observed in 3-day-old lambs. They were subsequently reduced throughout postnatal
      growth. A few prochymosin-immunoreactive cells were scattered in the glands of
      adult sheep. Pepsinogen immunoreactivity appeared at first in a small number of
      cells in the base of some proper gastric glands of 120-day-old fetuses. After 130
      days, pepsinogen-immunoreactive cells increased their staining intensities and
      distribution. They reached a peak in area at 21 days, which is comparable to
      adult sheep. In the pyloric glands, prochymosin- and pepsinogen-immunoreactive
      cells appeared from 100 and 130 days, respectively. Numbers were reduced in
      comparison to gastric glands and their occurrence was capricious. The results
      demonstrated that the ontogeny of prochymosin- and pepsinogen-immunoreactive
      cells in the abomasum of sheep is more similar to that in cattle than to that in
      the goat. The present data will contribute to the overall understanding of the
      development of ruminant gastric proteases.

PMID- 11534330
TI  - [The phylogenesis of equine teeth].
AB  - Phylogenetic research on the teeth of equidae beginning with dagger Hyracotherium
      ('Eohippus') will be summarized, subdivided into its components, analysed in a
      new way and finally interpreted according to several theories of evolution. In
      this context, specific cells (ameloblasts, odontoblasts, cementoblasts) are
      discussed and valued according to Preuss (1987) as active carriers of the
      evolution of teeth.

PMID- 11534331
TI  - Comparative macroanatomic investigations of the venous drainage of the heart in
      Akkaraman sheep and Angora goats.
AB  - This study was carried out to evaluate the origin, course and terminations of the
      cardiac veins in Akkaraman sheep and Angora goats. These vessels are the great
      cardiac, left marginal, middle cardiac, right cardiac and smallest cardiac veins.
      For this purpose, latex was injected into the jugular vein of eight adult healthy
      Akkaraman sheep and Angora goats. These veins were dissected. It has been shown
      that the middle cardiac vein and great cardiac veins coursed with the branches of
      the coronary arteries and that they were anastomosed with each other. The venous
      blood from the great cardiac vein and middle cardiac veins emptied into the right
      atria via the coronary sinus. The venous blood from the interventricular septum
      was conveyed to the middle cardiac vein and great cardiac veins.

PMID- 11534332
TI  - Ultrastructure of the spermatozoa from a Florida manatee (Trichechus manatus
      latirostris).
AB  - Semen was opportunistically collected from a free-ranging, 10-year-old, 275 cm
      (total length) Florida manatee (Trichechus manatus latirostris) during
      rehabilitation treatments. Ultrastructure of the spermatozoa was examined by
      scanning and transmission electron microscopy and differed slightly from that
      described for other mammals. Comparisons to the manatee's closest phylogenetic
      relatives, the elephant and hyrax, were made. The manatee spermatozoa had a
      similar acrosome but a distinct annulus and lacked the dense bodies observed in
      the neck of the elephant spermatozoa. Additionally, manatee spermatozoa lacked
      the lateral vacuoles observed in the nuclear chromatin from of the hyrax
      spermatozoa. These data add to our understanding of manatees and allow for
      comparative studies with other species that may be useful in phylogenetic and
      reproductive studies.

PMID- 11534333
TI  - [Benzilates--a review of their actions, synthesis and properties].

PMID- 11534334
TI  - Antituberculosis agents, I: Synthesis and antituberculosis activity of 2-aryl
      1,3,4-thiadiazole derivatives.
AB  - The design, synthesis and antituberculosis activity of a series of 2-aryl-5
      methylthio-1,3,4-thiadiazoles (5a-b), ethyl alpha-(5-aryl)-1,3,4-thiadiazole-2
      ylthio)acetates (8a-b) and related compounds are described. All of the compounds
      were tested against Mycobacterium tuberculosis strain H37Rv in comparison to
      rifampicin. Six compounds exhibited a very good activity (MIC < 6.25
      micrograms/ml, % Inhibition = 100).

PMID- 11534335
TI  - Synthesis and pharmacological activities of some new 2-[1-(6-methoxy-2
      naphthyl)ethyl]-6-(substituted)benzylidene thiazolo[3,2-b]-1,2,4-triazole-5(6H)
      one derivatives.
AB  - In this study, thirteen new compounds having a 2-[1-(6-methoxy-2-naphthyl)ethyl]
      6-(substituted)benzylidenethiazolo[3,2-b]- 1,2,4-triazole-5(6H)-one structure
      were synthesised using N-[2-(6-methoxy-2-naphthyl)propanoyloxysuccinimide, N-[2
      (6-methoxy-2-naphthyl)propanoyl]thiosemicarbazide and 3-[1-(6-methoxy-2
      naphthyl)ethyl]-5-mercapto-1,2,4-triazole. The structures and physical properties
      of the compounds were elucidated by IR, 1H NMR, mass spectroscopy and elemental
      analysis. The antiinflammatory activity and gastric ulceration potential of the
      compounds were tested using naproxen as a reference compound.

PMID- 11534336
TI  - Synthesis of 3-(3,4-dimethoxyphenyl)-1 H-1,2,4-triazole-5-thiol and 2-amino-5
      (3,4-dimethoxyphenyl)-1,3,4-thiadiazole derivatives exhibiting anti-inflammatory
      activity.
AB  - New 1-acylderivatives of 5-alkylthio-3-(3,4-dimethoxyphenyl)-4H-1,2,4-triazole
      (5c-f, 6d-f) were synthesized by the acylation of 5-alkylthio-3-(3,4
      dimethoxyphenyl)-4H-1,2,4-triazoles (3, 4) with acyl chlorides. The compounds 3,
      4 were obtained by the alkylation of 3-(3,4-dimethoxyphenyl)-1H-1,2,4-triazole-5
      thiol (2) sodium salt with alkyl iodides. Compound 2 and 2-amino-5-(3,4
      dimethoxyphenyl)-1,3,4-thiadiazole (8) were prepared by the treatment of 3,4
      dimethoxybenzoylthiosemicarbazide (1) with sodium hydroxide or acetyl chloride
      (and then sodium hydroxide), respectively. Related 2-acylamino-5-(3,4
      dimethoxyphenyl)-1,3,4-thiadiazoles (7c, e, f) were synthesized by the acylation
      of compound 8 with acyl chlorides. 3-(3,4-Dimethoxyphenyl)-4-phenyl-4,5-dihydro
      1H-1,2,4-triazole-5-thione (9) was N-acylated with acyl chlorides or S-methylated
      with iodomethane to give 1-acyl-3-(3,4-dimethoxyphenyl)-4-phenyl-4,5-dihydro-1H-
      1,2,4-triazole-5-thiones (10a, b) or 3-(3,4-dimethoxyphenyl)-5-methylthio-4
      phenyl-4H-1,2,4-triazole (11) respectively. The synthesized compounds 6d, 7a, c,
      10a, b, 11 exhibit anti-inflammatory activity.

PMID- 11534337
TI  - [Synthesis and pharmacologic action of chiral fomocaine ((4-[2-methyl-3
      (morpholin-4-yl)propyl)benzyl)-phenyl-ether and (4-(1-methyl-3-(morpholin-4
      yl)propyl]benzyl)-phenyl-ether). 13. Synthesis of new compounds with local
      anesthetic action].
AB  - The syntheses of two chiral fomocaines namely rac ((4-[2-methyl-3-(morpholin-4
      yl)propyl]-benzyl)-phenyl-ether (O/G 3) and rac (4-[1-methyl-3-(morpholin-4
      yl)propyl]benzyl)-phenyl-ether) (O/G 5) are reported. These compounds are part of
      a new research program concerning the relation between chirality and local
      anaesthetic activity in the group of fomocaines. The yield over five steps is in
      the range of 9% (O/G 3) up to 19.2% (O/G 5). The racemates were resoluted via the
      diastereomeric salts formed with (+)- or (-)-camphersulfonic acid. The
      chromatographic resolution in analytical scale is successful using a Daicel OD
      column. The enantiomers are stable. The surface anaesthesia of the racemates as
      well as of the enantiomeres is weaker in comparison with fomocaine. The rate of
      tissue irritation is higher. The LD50 (mouse i.v.) is in the range between 290
      390 mg/kg, while fomocaine shows a LD50 value of 175 mg/kg.

PMID- 11534338
TI  - HPLC analysis of S-adenosyl-L-methionine in pharmaceutical formulations.
AB  - A validated analytical method of S-adenosyl-L-methionine (SAM) in pharmaceutical
      preparations by reversed phase high performance liquid chromatography (RP-HPLC)
      is described. The compound is separated by a 2.1 mm x 15 cm, 5 microns--Discovery
      C18 column with isocratic elution. The effect of different anionic surface active
      agents with different molarity on the separation was studied. A direct
      relationship between the molarity of the surface active agents and the capacity
      factor (k') was found. The limit of detection was 0.49 mmol/ml and the linearity
      was r = 0.999 in the concentration range 20-100 micrograms/ml. Inter- and intra
      assay variation was determined for three selected concentrations (20, 60, 100
      micrograms/ml) by calculating the analytical recoveries with a range of 97.0
      99.9%. The procedure was also suitable to check the stability of S-adenosyl-L
      methionine in solution at room temperature.

PMID- 11534339
TI  - Determination of olsalazine sodium in pharmaceuticals by differential pulse
      voltammetry.
AB  - The electrochemical oxidation of olsalazine sodium was investigated by cyclic,
      linear sweep, differential pulse and square wave voltammetry using glassy carbon
      disc electrode in different buffer systems. Best results were obtained for the
      determination of olsalazine using the differential pulse voltammetric technique
      in phosphate buffer at pH 7.0. The electroactive species exhibits a diffusion
      controlled voltammetric wave and its differential pulse peak current shows a
      linear dependence on olsalazine concentration in the range between 2 x 10(-6) M
      and 2 x 10(-4) M. This relationship has been applied to the determination of
      olsalazine in commercial capsule dosage forms. The recovery study shows good
      accuracy and precision for the assay developed. A UV spectrophotometric assay is
      also reported for comparison.

PMID- 11534340
TI  - Liposome aggregation in presence of the sweeteners cyclamate and saccharine.
AB  - The interaction of the sweeteners saccharine and cyclamate with large unilamellar
      liposomes and planar bilayer lipid membranes (BLM) was studied. Application of
      the methods of light scattering and sound velocimetry showed that saccharine
      induces aggregation of liposomes, while cyclamate probably caused increase of the
      hydration of liposome surface. The sweeteners induced changes of BLM
      compressibility in a direction perpendicular to the membrane plane. The cyclamate
      induced considerably larger decreases in the elasticity module than saccharine.
      The obtained results show that both saccharine and cyclamate interacts with the
      surface of lipid bilayer and could modify the physical properties of lipid
      membranes.

PMID- 11534341
TI  - Bioequivalence of isoniazid in a two drug fixed dose combination and in a single
      drug dosage form.
AB  - To increase the patient compliance and reduce the risk of drug resistant strains,
      WHO and IUATLD recommend the use of Fixed Dose Combination (FDC) tablets as a
      routine therapeutic regimen in Directly Observed Treatment Shortcourse (DOTS).
      But the main issue in the use of FDC is the quality of the formulation. At
      present WHO and IUATLD suggest the bioequivalence assessment of only rifampicin
      from FDC compared to separate formulations. For the therapeutic effectiveness all
      the components of the FDCs should be bioavailable at tissue site. Also, the
      primary and acquired resistance rate of isoniazid is much higher compared to
      other anti-tubercular drugs. Hence, a comparative bioavailability study of
      isoniazid from a two drugs FDC compared to a separate formulation was carried out
      on a group of 12 healthy volunteers. When evaluated by normal or log transformed
      confidence interval, Two Way ANOVA and Hauschke analysis, the bioequivalence
      limits for AUC0-8 and AUC0-24 were within 0.8-1.25. For Cmax and Tmax, these
      limits were within 0.7-1.43. Hence, isoniazid from a FDC formulation was found to
      be bioequivalent to a separate formulation at same dose levels.

PMID- 11534342
TI  - Pharmacokinetics and tissue distribution of piperine in animals after i.v. bolus
      administration.
AB  - A reverse phase HPLC method to determine piperine, a pungent constituent of black
      pepper, in rabbit serum and various tissues of the rat was developed. A
      pharmacokinetic study was performed in rabbits and tissue distribution studies
      were carried out in rats. High reproducibility was achieved in quantitative
      analysis over the concentration range of 0.2-20 micrograms/ml serum. After bolus
      intravenous administration of piperine at a dose of 10 mg/kg, the serum
      concentration--time curve fitted the two-compartment open model. The tissue
      distribution pattern of piperine in rats also supports the two-compartment open
      model.

PMID- 11534343
TI  - Honey, a prospective antibiotic: extraction, formulation, and stability.
AB  - Old and recent reports show that honey has beneficial effects on the skin as
      antiseptic for wounds, burns and ulcers and as a healing promoter. Many
      investigators confirmed the usefulness of honey in the treatment of skin
      infections as well as internal diseases. The factors behind these effects are not
      completely explained. The aim of this study is: a) to investigate the
      antimicrobial activity of crude honey, b) to separate the fractions responsible
      for its activity, c) to formulate the honey extract as semisolid dosage forms, d)
      to study its release, and e) to determine its stability. The results showed that
      the ethylacetate honey extract showed antibacterial, anticandida and antifungal
      effects at low concentration. The release of honey extract from different
      ointment bases was depending on the constituents of the base, and its stability
      was found to be temperature and base dependent.

PMID- 11534344
TI  - Cytotoxicity of 2-aldo- and 2-ketopyridine-N(4)-substituted thiosemicarbazones
      and mode of action in human Tmolt4 cells.
AB  - The 2-aldo- and 2-ketopyridine-N(4)-substituted thiosemicarbazones and their
      copper complexes demonstrated potent cytotoxic activity against a series of
      murine and human suspended cultured tumor cells. Selected compounds were active
      against the growth of cultured cells from solid human tumors, i.e. Mck-7 breast
      effusion, lung A549 and lung MB-9812, bone SOS-2 and clear cell Caki renal tumor.
      In Tmolt4 T cell leukemia cells the compounds inhibited the syntheses of DNA, RNA
      and protein over 60 min at 25 to 100 microM. Multiple target sites in nucleic
      acid metabolism were suppressed by the agents, i.e. DNA polymerase alpha,
      ribonucleoside reductase, dihydrofolate reductase, de novo purine synthesis,
      thymidylate synthetase and nucleoside kinases. The total effects of the agents on
      DNA metabolism led to the reduction of deoxyribonucleotide pools as well as DNA
      fragmentation.

PMID- 11534345
TI  - Post-irradiation effect of Broncho-Vaxom, OM-85 BV, and its relationship to anti
      oxidant activities.
AB  - This study was conducted to test the efficacy of Broncho-Vaxom (OM-85 BV) in rats
      after exposure to radiation-induced oxidative stress. Daily administration of
      Broncho-Vaxom (2.5 mg/kg/day) to rats for a period of 28 days produced a
      progressive significant increase in the activities of superoxide dismutase (SOD)
      and catalase in lungs and erythrocytes. No changes were recorded in reduced
      glutathione (GSH) content in lungs, while an increase was recorded in
      erythrocytes. Significant increase was also observed in serum gamma-globulin
      content. Intraperitoneal administration of Broncho-Vaxom to rats for 11 days
      before gamma-irradiation and daily during the period of irradiation, delivered as
      1 Gy every other day to reach 9 Gy, significantly reduced radiation-induced lipid
      peroxidation (LPO) measured as thiobarbituric acid-reactive substances (TBARS) in
      the lungs and erythrocytes. Treatment with Broncho-Vaxom modified the radiation
      induced decrease of serum gamma-globulins contents. It is postulated that Broncho
      Vaxom, by enhancing the antioxidant system and increasing serum gamma-globulin
      content, could play an important role in modifying radiation-induced oxidative
      stress.

PMID- 11534346
TI  - Analgesic, diuretic, and anti-inflammatory principle from Scoparia dulcis.
AB  - Scoparinol, a diterpene, isolated from Scoparia dulcis showed significant
      analgesic (p < 0.001) and anti-inflammatory activity (p < 0.01) in animals. A
      sedative action of scoparinol was demonstrated by a marked potentiation of
      pentobarbital-induced sedation with a significant effect on both onset and
      duration of sleep (p < 0.05). Measurement of urine volume after administration of
      scoparinol indicated its significant diuretic action.

PMID- 11534347
TI  - A new flavone derivative from Ehretia ovalifolia leaves.
AB  - From the methylene chloride extract of Ehretia ovalifolia leaves, a new flavone
      derivative named ovalifolin [3-(3-methyl-1-butenyl)-6-methoxy-5,7,4'-trihydroxy
      flavone] has been isolated and identified together with the known flavone
      aglycones apigenin, luteolin and the highly methoxylated flavanol araneosol. The
      structures of these metabolites have been established on the basis of chemical,
      chromatographic and spectral methods.

PMID- 11534348
TI  - A new triterpenoidal saponin from Ixeris sonchifolia and its cytotoxic activity.
AB  - A new triterpenoidal saponin, echinocystic acid 3-O-beta-D-glucopyranosyl-(1-->3)
      alpha-L-arabinopyranoside (1), was isolated from Ixeris sonchifolia. Its
      structure was elucidated on the basis of full spectral data analysis and chemical
      methods. The cytotoxic activity of compound 1 was evaluated using the tumor cell
      lines of A375, Hela, and L929 in vitro.

PMID- 11534349
TI  - Synthesis of hexahydroquinoline derivatives possessing calcium antagonistic
      activity.

PMID- 11534350
TI  - Prediction of corneal permeability using polar molecular surface areas.

PMID- 11534351
TI  - Comparison of the stability of different tablet formulations containing folic
      acid, vitamin B6 and B12.

PMID- 11534352
TI  - Studies on dressings for mucosal oral cavity. Part 6: Influence of a solvent and
      1,2-propylene glycol on the pharmaceutic properties of dental xerogel dressings.

PMID- 11534353
TI  - Activity of calvatic acid and its analogs against Helicobacter pylori.

PMID- 11534354
TI  - [Bovine spongiform encephalopathy: a change in the etiology of the epidemic?].

PMID- 11534355
TI  - [Mesenteric venous thrombosis: early diagnosis with abdominal CT scan and
      screening for coagulopathies. Six observations].
AB  - PURPOSE: Mesenteric venous thrombosis is an uncommon entity whose diagnosis is
      difficult because the symptoms are nonspecific. Yet early recognition of this
      disease helps avoid the evolution towards mesenteric infarction. METHODS: We
      describe clinical symptoms and hypercoagulable states discovered in six patients
      with superior mesenteric venous thrombosis. RESULTS: Five of six patients were
      admitted to hospital for abdominal pain whose mean duration was 9 days before the
      diagnosis of venous thrombosis was made. Three of them had a fever. Two patients
      had a past history of deep venous thrombosis. All patients had a hypercoagulable
      state and three of them had two associated disorders of coagulation. In all
      cases, abdominal CT scan had permitted the diagnosis of mesenteric venous
      thrombosis. An anticoagulant therapy was conducted successfully in five of six
      patients. CONCLUSION: A CT abdominal scan done early in the case of nonspecific
      abdominal pain, since the patients had a previous history of venous thrombosis,
      may permit a nonsurgical treatment of mesenteric venous thrombosis. A screening
      for thrombophilia must always be carried out since coagulation disorders are very
      frequently the recognised causes in mesenteric venous thrombosis.

PMID- 11534356
TI  - [Fever and solid tumor: diagnostic value of procalcitonin and C-reactive
      protein].
AB  - PURPOSE: Evaluate the clinical utility of procalcitonin (PCT) and C-reactive
      protein (CRP) as diagnostic of paraneoplastic fever. METHOD: A prospective
      analysis of serum levels of PCT and CRP has been conducted on 68 consecutive
      febrile patients with solid tumour and no neutropenia. The samples were collected
      at hospital admission. RESULTS: Out of 68 patients, 57 had head and neck cancer.
      Forty-three patients had signs of infection and 19 had paraneoplastic fever. CRP
      was not significantly different between the two groups (infected patients:
      median: 134 mg/L, extremes: 20-569; paraneoplastic fever patients: median: 154
      mg/L, extremes: 26-267; P = 0.75 with Mann-Whitney test). On the other hand, PCT
      was significantly higher in case of infection (median: 0.44 ng/mL, extremes: 0.09
      57.4) than in the case of paraneoplastic fever (median: 0.26 ng/mL, extremes:
      0.05-1.17; P = 0.01 with Mann-Whitney test). CONCLUSION: In our study, no
      paraneoplastic fever patient had PCT level equal or above 2 ng/mL (negative
      predictive value of 100%).

PMID- 11534357
TI  - [Study of methicillin-resistant Staphylococcus aureus colonization among
      intermediate-care facility patients].
AB  - PURPOSE: Prevalence of methicillin-resistant Staphylococcus aureus is high in the
      Poitiers teaching hospital, particularly in the intermediate care facilities. We
      performed a survey of methicillin-resistant Staphylococcus aureus colonization in
      the intermediate care facilities and 265 patients were included. METHODS: Nasal,
      cutaneous and wound swab cultures were done at the time of admission and at the
      time of the patients' departure. A decolonization procedure of methicillin
      resistant Staphylococcus aureus carriers was performed using nasal application of
      fusidic acid and different soaps for the skin. At entry, 17.7% of patients were
      methicillin-resistant Staphylococcus aureus carriers (of at least one location).
      At departure, 30.4% were methicillin-resistant Staphylococcus aureus carriers.
      Among methicillin-resistant Staphylococcus aureus non-carriers at entry, 24.3%
      became methicillin-resistant Staphylococcus aureus carriers. RESULTS: The
      principal risk factor of carriage was the initial presence of a wound (RR = 3.6).
      The incidence rate of methicillin-resistant Staphylococcus aureus infection among
      the 265 patients included was 3%. CONCLUSION: The systematic screening of
      patients at the time of admission is expensive and isolation technically hard to
      manage in the intermediate care facilities. The risk factor we found in this
      study allow us to propose a 'light' screening limited to patients with wounds.

PMID- 11534358
TI  - [Clinical diagnosis of overtraining using blood tests: current knowledge].
AB  - PURPOSE: Overtraining results from an imbalance between training load-induced
      fatigue and organism's recovery abilities. Its etiology is complex and to date
      there is no useful clinical diagnostic tool. The purpose of this review is to
      discuss the blood chemistry parameters potentially useful for diagnosing
      overtraining in athletes. CURRENT KNOWLEDGE AND KEY POINTS: Chronic alterations
      of the myocyte structure may cause high plasma concentration increases of
      myoglobin, troponin I and creatine kinase enzyme, resulting in chemical and/or
      mechanical aggression. Monitoring reactive oxygen species' activity appears to be
      a good tool for evaluation of the metabolic stress level experienced by skeletal
      muscles. In energetic metabolism, a succession of chronic glycogen depletions
      might change the use of amino acids and lipids, inducing transient but severe
      hypoglycemia during exercise. A higher oxidation of circulating glutamine might
      cause immunosuppression (lower reactivity to inflammations and cellular
      traumatisms), inhibiting alarm signals during acute training. A higher branched
      chain amino acid oxidation might favor free tryptophan's entry into the cerebral
      area, enhancing serotonin synthesis. As a consequence, asthenia and a loss of
      sensitivity to muscular and tendon traumatism might appear. Exercise anemia might
      also be a worsening factor of the physiological situation of the tired athlete,
      inducing predisposition to overtraining by the lower inflammation reactivity of
      depleted hepatic and muscular proteins. FUTURE PROSPECTS AND PROJECTS: Early
      diagnosis of overtraining diagnosis may be established only from a battery of
      analyses, which should include the whole of the potential parameters. These
      remain unpredictable and do not allow systematic determination of new cases. Only
      a longitudinal study of the physiological situation appears to allow the
      necessary conditions for detecting overtraining in the early stages of its
      process for each subject.

PMID- 11534359
TI  - [Economic impact of rationalized antibiotic therapy in a general hospital].
AB  - PURPOSE: To evaluate the economic impact and the bacterial resistance rates after
      2 years of a rationalized antibiotic prescription program in a 502-bed hospital.
      CURRENT KNOWLEDGE AND KEY POINTS: Prescribing protocols were established by
      consensus in 1998 and were reinforced a year later by nominative dispensing of
      the most costly antibiotics. The impact of the program was assessed in terms of
      changes in the overall cost of antibiotics and in the pattern of bacterial
      resistance among pathogens isolated in the institution, during the period prior
      to the onset of the program (1997) and its realization (1998 and 1999). FUTURE
      AND PROJECTS: The expenses for antibiotic drugs decreased by 46% in 2 years.
      Resistance rates among the different pathogens studied have remained stable. No
      increase of mortality was observed. Our rational policy in antibiotic therapy had
      a positive economic impact. However, new additional measures should be encouraged
      to prevent antimicrobial resistance.

PMID- 11534360
TI  - [Papillary fibroelastoma: a rare but treatable cause of cerebral infarction].
AB  - INTRODUCTION: Papillary fibroelastoma is a benign cardiac tumor which can be
      associated with serious embolic complications. EXEGESIS: We report on a 42-year
      old man admitted for an ischemic stroke in the left middle cerebral artery
      region. Transesophageal echocardiography revealed a mitral valve tumor. Surgical
      excision and histological examination showed a papillary fibroelastoma. Clinical
      course was uneventful. CONCLUSION: We consider the high embolic potential of this
      tumor, which represents a surgically treatable cause of ischemic stroke.

PMID- 11534361
TI  - [Crohn's disease and small intestine adenocarcinoma].
AB  - INTRODUCTION: The relationship between digestive neoplasia and Crohn's disease
      remains debated but several cases of carcinoma have been reported in the past 10
      years. EXEGESIS: We report two cases of intestinal adenocarcinoma found in young
      people. Patients were asymptomatic during 15 years after the diagnosis of
      inflammatory bowel disease and presented a sudden occlusive syndrome. Carcinoma
      was observed incidentally at gross examination, and histopathological study
      showed dysplasia adjacent to neoplasia. Despite adequate surgical resection,
      death occurred quickly. CONCLUSION: Crohn's carcinoma should be suspected in
      patients with long-standing disease, poor symptomatology, and stenosis.
      Intestinoscopy surveillance remains illusory because inflammatory stenosis is
      often present and infiltrative neoplasia is invisible. Thus, it is important to
      be vigilant in this clinical presentation.

PMID- 11534362
TI  - [Stewart-Treves syndrome following mastectomy for breast cancer: a case report].
AB  - INTRODUCTION: Stewart-Treves syndrome has been defined by the eponymous authors
      as a lymphangiosarcoma in a setting of postmastectomy upper extremity
      lymphoedema. EXEGESIS: The clinical record of one patient with Stewart-Treves
      syndrome is analyzed. The primary angiosarcoma of the skin represented by a
      purple nodule occurred on a chronic lymphoedematous arm following radical
      mastectomy and axillary lymph node dissection for breast carcinoma performed 9
      years earlier. Immunohistochemistry tests formally eliminated epithelial
      cutaneous metastasis and produced evidence in favour of conjunctive vascular
      tissue origin of the tumor. CONCLUSION: Conservative surgery for breast cancer,
      application of axillary sentinel node biopsy in the lymphatic staging and
      prevention of arm lymphoedema should reduce the incidence of this syndrome.

PMID- 11534363
TI  - [A pseudotumorous mediastinal lesion].

PMID- 11534364
TI  - [Miller-Fisher syndrome with quadriplegia, respiratory attack, and dysautonomia].

PMID- 11534365
TI  - [Hemorrhagic accidents with low molecular weight heparin: 15 cases].

PMID- 11534366
TI  - [Glomerulonephritis revealing a thymus tumor in a patient with myasthenia
      gravis].

PMID- 11534367
TI  - [Hypothermia induced by neuroleptics. Clinical case report].

PMID- 11534368
TI  - Infrastructure issues hold key to future success under risk.

PMID- 11534369
TI  - IN medical group making capitation work by carefully adhering to management
      tenets.

PMID- 11534370
TI  - Pacificare still bullish on capitation as it plans new tiered benefit program.

PMID- 11534371
TI  - Will new NJ law regulating at-risk entities become a model for other states?

PMID- 11534372
TI  - New venture pins its hopes on future of Medicare+Choice.

PMID- 11534373
TI  - [Prenatal genetic counseling in pregnancy: the importance of (early) timely
      referral ].
AB  - Three women aged 34, 23 and 39 years, who were respectively, 14, 12 and 8 weeks
      pregnant, requested genetic counselling due to grave genetic diseases in their
      families. The first woman chiefly wanted to be prepared; an investigation
      revealed no abnormalities and a healthy child was born. The second needed time to
      assimilate the information provided and terminated the pregnancy. For the third
      woman genetic screening was not possible in the short term and furthermore
      acceptation of the pregnancy was the biggest problem; she gave birth to a healthy
      child. In the Netherlands, about 800 to 1600 women every year request prenatal
      genetic counselling when they are already pregnant. The disadvantages of this
      late timing are the disquiet and uneasiness, the lost options and the time
      pressure under which difficult decisions have to be taken. Causes of this are a
      lack of genetic knowledge and psychosocial aspects. Ideally, genetic counselling
      that deals with reproductive issues should take place prior to conception.

PMID- 11534374
TI  - [High vacuum extraction: justifiably obsolete in view of the risks to the
      infant].
AB  - The author was asked to provide an expert assessment of the case histories of 28
      patients delivered by vacuum extraction. At the start of the extraction the
      foetal head level was at station 0 or above in 25 of the patients. In 12 cases
      the duration of extraction exceeded 14 min and in 7 of the cases it exceeded 19
      minutes with a maximum of 45 minutes. Nine of the infants died, 11 suffered
      cerebral damage, 4 had brachial plexus injury and 1 had both cerebral damage and
      plexus injury. In 17 cases a causal relation between the unfavourable outcome and
      the vacuum extraction seemed plausible. During the past 40 years several studies
      of patients who have undergone high pelvic vacuum extractions have been
      published; cerebral damage of the infants often occurred. The risk of shoulder
      dystocia resulting in brachial plexus injury is considerably increased in case of
      a large infant and mid pelvic or high pelvic delivery. In the paediatric
      literature a number of authors describe cerebral lesions caused by high pelvic
      vacuum extraction. High pelvic vacuum extraction is still occasionally practiced
      in the Netherlands; it is a hazardous technique and should be replaced by
      caesarean section.

PMID- 11534375
TI  - [CBO guidelines 'Antiretroviral therapy in the Netherlands'].
AB  - In collaboration with the Dutch Institute for Health Care Improvement (CBO) and
      on the basis of recent developments, new guidelines have been developed for the
      diagnosis and treatment of HIV-infected patients. The most important
      recommendations are: Treatment of adult patients is indicated if HIV load >
      30,000 RNA copies/ml, or when CD4+ cell count is < 350 x 10(6) cells/l. Treatment
      of children is indicated if HIV load > 5,000 copies/ml, even when CD4+ cell count
      is > 500 x 10(6) cells/l. Optimal antiretroviral treatment consists of a
      combination of two nucleoside reverse transcriptase inhibitors (NRTIs) and one
      protease inhibitor, or a combination of two NRTIs and one non-nucleoside reverse
      transcriptase inhibitor. Patients on antiretroviral treatment should be monitored
      every 3 months. Undetectable HIV load should be the target of first- or second
      line antiretroviral treatment. In order to prevent HIV transmission from mother
      to child, prescription of antiretroviral drugs after the first three months of
      pregnancy is indicated in pregnant women with a detectable HIV load. Prophylaxis
      of opportunistic infections can be discontinued if CD4+ cell count recovers above
      200 x 10(6)/l. In case of exposure to HIV due to a needle or other occupational
      accident or unsafe sexual contact, post-exposure prophylaxis should be offered
      after careful risk evaluation. Preferably, vaccination to prevent pneumococci
      infections, influenza, hepatitis A or hepatitis B should be given when CD4+ cell
      count is > 200 x 10(6)/l.

PMID- 11534376
TI  - [Diagnostic image (51). Right-sided endocarditis in a heroin addict ].
AB  - A 23-year-old heroin addict was admitted with coughing, haemoptoe and fever.
      Right-sided endocarditis was diagnosed.

PMID- 11534378
TI  - [Increased percentages of breastfed infants in Amsterdam].
AB  - OBJECTIVE: To investigate the prevalence of breastfeeding amongst infants in
      Amsterdam prior to and following an active breastfeeding policy that has been
      operating in Amsterdam since 1993; investigate the link between ethnic origin and
      breastfeeding and the reasons mothers give for stopping breastfeeding. DESIGN:
      Retrospective, descriptive study. METHOD: During the period 1998 to 2000, 1274
      mothers in six child health centres in Amsterdam, the Netherlands, were asked
      about how they had fed their infant, aged 6 to 8 months, from the first week
      onwards, and their reasons for starting formula feeding. The breastfeeding
      percentages were compared with a study for the period 1992 to 1993. RESULTS:
      During the first week of the infant's life, 87% of the mothers gave
      breastfeeding, and at 25 weeks this figure was 30%. For the period 1998 to 2000,
      the breastfeeding rate at 15 weeks was higher compared with the period 1992 to
      1993, 45.1% as opposed to 36.4%. An increased percentage of breastfed infants
      were found in each ethnic group studied. More Turkish and Moroccan mothers than
      Dutch mothers started to breastfeed, and they breastfed for a similar period.
      Surinam mothers started breastfeeding as often as Dutch mothers, but breastfed
      for a shorter period. Concern about inadequate milk supply was stated as the most
      important reason for starting formula feeding (44%). This was also the most
      important reason stated by each of the ethnic groups, Dutch (139/411; 34%),
      Surinam (63/129; 49%), Moroccan (70/130; 54%) and Turkish women (42/67; 63%).
      CONCLUSION: An active breastfeeding policy in Amsterdam that has been operating
      since 1993 has been accompanied by an increase in the number of breastfed
      infants. This has also been the case in non-Dutch groups. Health programmes
      should devote greater attention to mothers' concerns about a shortage of milk.

PMID- 11534377
TI  - [HIV-1 therapy in the Netherlands; virological and immunological response to
      antiretroviral therapy].
AB  - OBJECTIVE: To evaluate the effect of treatment of HIV-1 infection with
      combination therapy consisting of since 1996 in the Netherlands available
      protease and reverse transcriptase inhibitors. DESIGN: Prospective cohort study.
      METHODS: In an observational clinical cohort of HIV-1-infected individuals, the
      short-term successful treatment end point of antiviral therapy including at least
      one antiretroviral drug licensed in the Netherlands since July 1, 1996 (protease
      inhibitors and reverse transcriptase inhibitors), was HIV-1 RNA plasma levels <
      or = 500 copies/ml (virological success). Cox proportional hazard models were
      used to identify prognostic markers for therapy success. The study included 2,148
      infected individuals with a median follow-up of 135 weeks of treatment; 1,049 had
      been pre-treated with antiretroviral drugs before starting their new regimen and
      1,099 were treatment naive. RESULTS: Plasma HIV-1 RNA levels < or = 500 copies/ml
      at 24 weeks of treatment were seen in 61% of all patients. The chance of therapy
      success for naive patients was twice that for pre-treated patients (relative
      risk: 1.8; p < or = 0.001). Following the first 24 weeks, the chance of
      virological success was higher in the naive group (78% versus 63%; p < or =
      0.001), and the number of naive patients failing therapy after initial success
      was smaller compared to pre-treated patients (22% versus 45%; p < or = 0.001). In
      the naive group, the CD4+ T-cell number increased from 239 to 440 (x 10(6)
      cells/l) in case of success, and decreased from 150 to 320 in case of treatment
      failure. HIV-1 related morbidity declined from 0.26 to 0.05 and mortality dropped
      from 0.07 to 0.03 per person-year of follow-up. Regimens were changed at least
      once in 76% of patients. Toxicity and therapy failure were the main reasons for
      regimen changes in naive and pre-treated patients, respectively. CONCLUSION: A
      combination of antiretroviral drugs, including at least one of the drugs licensed
      since 1996, led to a drop in HIV-1 plasma concentrations. Morbidity and mortality
      also decreased. The chance of a better immunological and virological response to
      the new drug regimens was greatest in therapy-naive patients.

PMID- 11534379
TI  - [Aneurysm of the V. magna cerebri (vein of Galen), a cause of congestive heart
      failure in five neonates].
AB  - In five neonates (4 girls and 1 boy) with aneurysm of the V. magna cerebri,
      clinical signs of congestive heart failure were encountered. In three of the
      neonates the symptoms were detected postnatally and in two prenatally. In one of
      the prenatally detected cases the aneurysm was treated by embolisation during the
      first week of life. Upon follow-up at six years of age, this patient's situation
      was stable but hydrocephalus had led to poor visuomotor development, mild motor
      retardation and mental retardation. In the other infants, medicinal treatment of
      the congestive heart failure was discontinued in view of ischaemic brain damage,
      and these patients subsequently died. Congestive heart failure often develops in
      neonates with an aneurysm of the V. magna cerebri due to low cerebrovascular
      resistance. A continuous murmur over the skull is pathognomonic for this
      condition.

PMID- 11534380
TI  - [National hepatitis B vaccination closer to implementation, but not soon enough;
      recommendation from the Dutch Health Council].

PMID- 11534381
TI  - [Physical diagnostics--duplex scanning is necessary only for patients with
      varicose veins].

PMID- 11534382
TI  - [Physical diagnostics--peripheral arterial disease].

PMID- 11534383
TI  - Professor Uwe E. Reinhardt. James Madison Professor of Political Economy at the
      Woodrow Wilson School of Public and International Affairs at Princeton
      University.

PMID- 11534384
TI  - A safe environment for all.

PMID- 11534385
TI  - Restoring the purpose of medicine.

PMID- 11534386
TI  - Countdown to HIPAA in New Jersey.

PMID- 11534387
TI  - Medical board expectations for the delivery of pain management care to patients.

PMID- 11534388
TI  - The effects of socioeconomic and socioenvironmental factors on the self-reported
      health of elderly blacks and whites.

PMID- 11534389
TI  - Professional liability insurance: III. The clinical environment.

PMID- 11534390
TI  - Recognizing the need for graduate medical education.

PMID- 11534391
TI  - Health care and economics.

PMID- 11534392
TI  - [Formation of TRA-dependent surface structures in Agrobacterium tumefaciens and
      their absence in R1 (deltatraR) mutant].
AB  - Agrobacteria have Ti plasmid DNA delivering systems for the transfer to recipient
      cells by the conjugation mechanism. This transfer is absolutely dependent on
      induction tra genes. It is not clear which tra-dependent surface (extracellular)
      proteins (structures) are involved in the transport mechanism and whether these
      proteins also play a role in the contact formation. SDS-PAGE electrophoresis of
      proteins released from the cell showed disappearance of 63 and 67 kD proteins in
      R1(delta traR) strain, which were found in the growth medium and triton extract
      from the outer membrane of Ti plasmid-harboring A. tumefaciens R10 strains. The
      traR defective mutant did not express these proteins and had a higher
      hemagglutination and flocculation capacity than the wild strain. On the other
      hand, the wild strain showed D-galactose and N-acetyl-galactosamine specific
      hemagglutination which was not shown by traR mutant. Motility and chemotactic
      behavior of traR mutant in semisolid medium were defective. As a rule, one (or
      rarely two) thread-like connections in vir(-) and tra(+) conditions were observed
      on the agrobacterial cell surface. SDS pretreatment of agrobacterial cells had a
      significant effect on the expression of tra-dependent surface structures.

PMID- 11534393
TI  - [Modulation of the cat gene expression in E. coli cells by simple (AC)20
      repeats].
AB  - Probable relationship between modulation of gene expression by simple repeating
      sequences and competition capacity of the host was studied. (AC)20 repeat can
      both stimulate and inhibit the expression of chloramphenicol acetyl transferase
      gene expression in E. coli cells depending on this gene's position. Modulation of
      the gene expression by simple (AC)20 repeat and competitive capacity of bacteria
      containing this plasmid are closely related.

PMID- 11534394
TI  - [HindIII polymorphism of lipoprotein lipase gene and risk of myocardial
      infarction].
AB  - The purpose of this study was to determine whether HindIII restriction
      polymorphism found in intron 8 of lipoprotein lipase gene is associated with the
      onset of myocardial infarction (MI) in Russians and Tartars living in
      Bashkortostan. HindIII polymorphism was investigated by the polymerase chain
      reaction in myocardial infarction survivors (males aged under 55 years (98
      Russians and 68 Tartars) and in controls (53 Russians and 80 Tartars). The
      distribution of genotypes and allele frequencies in the controls were as follows:
      the frequencies of genotypes HindIII(-/-), HindIII(+/-), and HindIII(+/+) in
      Russians (3.77, 49.06, and 47.17%, respectively) did not differ from those in
      Tartars (7.50, 51.24, and 41.25%, respectively), while the frequency of HindIII(
      ) allele was 28.30% in Russians and 33.13% in Tartars. Among Tartars, the
      HindIII(+/+) genotype was more common in myocardial infarction survivors than in
      controls (OR 2.03). In the Russians this genotype was not associated with the
      risk of MI. The frequencies of HindIII(+/+) genotype and allele HindIII(+) were
      significantly higher (OR 8.96 and 6.71, respectively) and frequencies of
      HindIII(+/-) genotype and allele HindIII(-) were lower (OR 0.13 and 0.15) in
      Russian patients with repeated MI. These findings indicate that HindIII
      polymorphism may be a genetic risk factor for MI before 55 years of age in the
      Tartars and for repeated MI in Russians. This association prompts genotyping of
      HindIII polymorphism for predicting MI recurrence in Russian survivors after MI.

PMID- 11534395
TI  - [Prevalence of major virulence genes among various Vibrio cholerae El-TOR strains
      for evaluating their epidemiological significance].
AB  - Specific oligonucleotide primers were chosen for identifying the fragments of the
      four major virulence genes of V. cholerae eltor (ctxA, tcpA, toxR, and hap) using
      the polymerase chain reaction (PCR). In order to estimate the efficiency of
      complex PCR testing of V. cholerae for evaluation of their epidemiological
      significance, a collection of 80 V. cholerae eltor strains with known virulence
      was selected, whose most important specific features had been studied previously.
      The hap was appropriate species-specific gene making it possible to detect V.
      cholerae strains regardless of their virulence. The most complete and objective
      data for evaluating the epidemic significance can be obtained by detecting the
      presence of three virulence genes (ctxA, tcpA, and toxR) in their chromosome. The
      prevalence of the above four genes in various V. cholerae strains isolated from
      the environment during epidemic and non-epidemic periods was studied.

PMID- 11534396
TI  - [Monoclonal antibodies for studying antigens of protein origin in serotyping of
      Yersinia pseudotuberculosis].
AB  - Hybridomas producing monoclonal antibodies (MAb) to Yersinia pseudotuberculosis,
      serovars I-IV, responsible for serovar appurtenance, were obtained. Virtually all
      MAbs reacted with protein antigens in immunoblotting. The only exclusion was MAb
      3A2 presumably reacting with a glycoprotein epitope of complex structure.
      Variability of Y. pseudotuberculosis antigenic structure, depending on culturing
      temperature, was confirmed. Polypeptides with mono- or polydetermined antigenic
      specificity were determined using MAbs.

PMID- 11534397
TI  - [Active membrane transport and bacterial multiple antibiotic resistance].
AB  - Multiple drug resistance can form in bacteria by functioning the membrane
      transport systems, responsible for release of antibacterial compounds from the
      cell into the environment. These transport mechanisms activated in the majority
      of cases by energy of proton transmembrane gradient are presented by solitary
      membrane transporting proteins and by functionally related transporter groups,
      periplasma proteins, and external membrane porines. Many bacterial drug
      transporters can bind and transfer a number of structurally heterogeneous
      substrates. Drug transporters known today have different origin and primary
      physiological functions. The genetic system of transporter type drug resistance
      is as a rule characterized by a cluster structure and related to mobile genetic
      elements. Transport mechanisms of drug resistance create an extra adaptation
      potential of microorganisms under conditions of selective pressure.

PMID- 11534398
TI  - [Morphology of Streptomyces chrysomallus microcolonies in submerged cultivating].
AB  - Gel matrix covering microcolonies and individual hyfs and cords of mycelial hyfs
      was for the first type detected using a special method for making preparations
      for microscopic examinations. The matrix is observed during culturing
      streptomycetes in media of different composition for mycelium of different age.
      Gel matrix renders the colonies a compact shape and can be regarded as a specific
      structural component of Streptomyces microcolonies. The matrix contains gels
      differing by hydrophobicity and low-molecular-weight biosynthesis products,
      including actinomycin antibiotics, which play an important role in maintenance of
      morphological structure.

PMID- 11534399
TI  - [Differential gene expression in culturable and non-culturable Salmonella
      typhimurium].
AB  - Differential gene expression in culturable and non-culturable forms of Salmonella
      typhimurium was studied by the molecular display method. Six fragments of
      differentially expressed gene cDNA, depending on culturable or non-culturable
      state of the cultures, were isolated, cloned, and sequenced. Identification of
      corresponding S. typhimurium differentially expressed genes was carried out by
      comparing the sequences of cDNA fragments with the bacterial genome data base.

PMID- 11534400
TI  - [Partial nephrectomy in renal cell carcinoma].
AB  - INTRODUCTION AND OBJECTIVES: Renal Cell Carcinoma (RCC) represents 3% of all
      neoplasm. The growing incidental diagnosis of small renal tumor has allowed the
      application of nephron sparing surgery (NSS), even in those cases with a normal
      contralateral kidney. We present the results of NSS at our center in the last
      decade. MATERIAL AND METHODS: A retrospective analysis of all NSS that were made
      at our center in cases of renal masses. Difference is made between elective
      surgery (tumors less than 4 cm with a normal contralateral kidney) and obligatory
      surgery (all other cases). RESULTS: From 1990 since 2000 a total of 65 NSS were
      made from a total of 436 surgeries for renal tumors (14.9%). In 22 patients NSS
      was obligatory, while in 43 was elective. Mean (SD) age was 59.1 years (+/-
      11.7), mean tumor size 3.4 cm (+/- 1.4), mean hospital staying was 9.2 days (+/-
      7). Renal normothermic ischaemia was use during surgery in all cases, with a mean
      ischaemic time of 25.7 min. Nine tumors (13.8%) were benign. Morbidity: 10.8%.
      Mortality: 1.5%. The cancer specific survival at 36 months of follow-up (mean
      37.4) is 98.4% and global survival is 90.3%. CONCLUSIONS: Nephron Sparing Surgery
      is a valid alternative in the treatment of RCC, specially for tumors less than 4
      cm in diameter and having a normal contralateral kidney; NSS is also an effective
      technique for patients bearing renal tumors in a solitary kidney.

PMID- 11534401
TI  - [Enterocystoplasty in the treatment of interstitial cystitis].
AB  - OBJECTIVE: To evaluate supratrigonal cystectomy and enterocystoplasty in patients
      with interstitial cystitis. METHODS: We reviewed four women with interstitial
      cystitis with infructuos conservative treatment and performed supratrigonal
      cystectomy and enterocystoplasty. All the patients fulfilled the NHI criteria
      with increased voiding frequency by night (mean 7.3 times). In 3 cases urodynamic
      study was available. We used is the four patients ileon as segment for the
      enterocystoplasty. RESULTS: Mean postoperative follow up was 60 months. In all
      cases the suprapubic pain disappeared and night voiding frequency reduced (mean
      2.2 times). We don't have mayor complications. One patient needs self catheterism
      3 years after surgery. CONCLUSION: In patients with interstitial cystitis to be
      operated supratrigonal cystectomy and enterocystoplasty is the most effective
      method.

PMID- 11534402
TI  - [Percentage of tumor in prostatic biopsy cylinders as prognosis factor of organ
      limited disease in candidates for radical prostatectomy].
AB  - The present study analyzes the prognostic influence of tumor percentage in
      cylinders of prostatic biopsy in this patient group. MATERIAL AND METHODS:
      Retrospective study of 68 patients with a diagnosis of adenocarcinoma, clinical
      stage T1-T2 who had undergone a radical prostatectomy from May 1997 to october
      2000. Following preoperative parameters were analyzed: age, PSA, clinical
      staging, Gleason and six cylinders of ultrasonography-leaded transrectal
      prostatic biopsy, studying the amount of positive biopsies, the tumor percentage
      of the total amount of biopsies and the maximum percentage of tumor in one
      cylinder. Univariate (square-Chi, Student t) and multivariate (multiple logistic
      regression) analysis are performed in order to study the relationship of these
      parameters with the presence or not of an organ-located disease. RESULTS: An
      organ-located disease was shown at 44 patients through the piece of radical
      prostatectomy. The univariate analysis gave all studied parameters, except age, a
      prognostic value of the existence or not of an organ-located disease. In the
      multivariate analysis only the total percentage of biopsy tumors (p = 0.0002) and
      PSA (p = 0.005) behaved as independent prognostic factors. CONCLUSION: Tumor
      percentage in prostatic biopsy seems to be a factor with a high predictive value
      of an organ-located disease, possibly because it is an index of tumoral volume.

PMID- 11534403
TI  - [Comparative study of ureteral anastomosis with or without double-J
      catheterization in renal transplantation].
AB  - OBJECTIVE: To analyze the impact of the use of the routine double-J stent in the
      incidence of urological complications, like fistula, stenosis, ureteral
      obstruction and urinary tract infection. METHODS: A retrospective study was
      conducted on two groups of patients: 28 without double-J stent and 28 with it. We
      reviewed urological complications: stenosis, fistula and obstruction. We paid
      special attention to urinary tract infection and other inherents complications to
      the use of double-J stents. RESULTS: A patient from the double-J stended group
      (3.6%) developed a urinary fistula and there were no obstructions. 13 patients
      (46.6%) had a positive urinary culture in the first month post RT. Two urinary
      fistulas and 4 obstructions were developed in the non-stended group. Six major
      complications of the urinary tract. 14 patients (50%) had a positive urinary
      culture in the first month post RT. CONCLUSIONS: The use of double-J stent across
      uterovesical anastomosis decreases the post-RT ureteral complications. Stent
      placement does not increase the risk of urinary tract infection in the early post
      RT.

PMID- 11534404
TI  - [Treatment of bladder lithiasis with shock-wave extracorporeal lithotripsy].
AB  - PURPOSE: To evaluate the effectiveness and the prognostic factors of the bladder
      stones (BS) treatment by means of extracorporeal shock wave lythotripsy (ESWL).
      METHODS: 183 patients with BS treated using ESWL were retrospectively analysed.
      Independent variables were: gender, age, obstruction, BS size, BS number and
      amount of waves. Dependent variable was total BS resolution. Statistical analysis
      was provided by Cox's regression multivariate analysis, Kaplan-Meier analysis and
      the t Student test. RESULTS: Total effectiveness of the treatment was 73%.
      Initial BS size was the only prognostic factor on multivariate analysis (p =
      0.0035) with smaller stones obtaining the best results (log rank p = 0.00001):
      92% of effectiveness in BS smaller than 1 cm2, 73% in 1-2 cm2, 57% in 2-3 cm2 and
      42% in larger than 3 cm2. BS mean size decreased 2 cm2 after the first ESWL (p =
      0.00001). CONCLUSIONS: Initial BS size was the only prognostic factor of
      resolution. Total effectiveness was 73% and it highly increased in BS smaller
      than 2 cm2.

PMID- 11534405
TI  - [Acute renal infarction. Report of 2 cases].
AB  - Diagnosis of acute renal infarction is often delayed or missed due to both the
      rarity of the disease and its unespecific clinical presentation. Definitive
      radiologic diagnosis often requires invasive procedures such as angiography.
      Computed tomography (CT) may be useful in diagnosing acute renal infarction and
      is considered the standard of reference for diagnosis of acute renal infarction,
      with the advantage of being non-invasive and potentially available 24 hours a
      day. We report two cases, in the first case we show a segmentary renal
      infarction; at the second one we report a case of complete renal infarction.
      Presentation, diagnosis and therapeutic aspects are discussed.

PMID- 11534406
TI  - [Squamous cell carcinoma of the renal pelvis. A clinical case].
AB  - Squamous cell carcinoma of the renal pelvis is uncommon, accounting for
      approximately 10% of all renal pelvic tumours. It's often associated with chronic
      renal calculi or infection and it usually presents at an advanced stage with pain
      or a palpable mass. We report an incidental case of squamous cell carcinoma of
      the renal pelvis, associated with chronic renal calculi and infection, and weight
      loss. The prognosis of patients with advanced squamous cell carcinoma of
      genitourinary origin is poor. In patients with chronic stones or infection
      squamous cell carcinoma of renal pelvis must be suspected if survival is to be
      affected.

PMID- 11534407
TI  - [Post-traumatic high flow priapism in a child].
AB  - We report on the case of a post-traumatic high-flow priapism in a 14 year-old
      boy, which was confirmed by cavernous blood gas measurement color flow Doppler
      sonography, and arteriography. It was successfully treated with superselective
      embolization of the right internal pudendal artery, resulting a clear
      disappearance of cavernus rigidity.

PMID- 11534408
TI  - [Retroperitoneal leiomyosarcoma].
AB  - We report a case of retroperitoneal leiomyosarcoma recurrence. This entity is
      rare, < 0.2% of all tumours in humans and 25-30% of retroperitoneal sarcomas. The
      diagnosis is usually delayed in relationship with scarce clinical signs which
      favorite the development of great tumour volume before diagnosis. The treatment
      is surgical, with wide margins excision. Radiotherapy and chemotherapy are not
      adequates for treatment of this pathological entity.

PMID- 11534409
TI  - [Retroperitoneal liposarcoma in a patient with renal transplantation].
AB  - A case of retroperitoneal sarcoma in a kidney transplanted patient is presented.
      We describe the presentation pattern and the aggressive outcome despite the
      surgical removal of 5.900 gr. retroperitoneal tumor, included native kidney. The
      patient died due multiple metastasis six months later. An interesting iconography
      shows the great volume of the tumor.

PMID- 11534410
TI  - [Primary bladder amyloidosis].
AB  - Primary amyloidosis of the bladder is a rare disease entity manifested as
      extracellular deposits of a fibril protein in an amyloid substance form. Clinical
      presentation resembles a bladder tumor, as hematuria is the most common clinical
      manifestation. Single organ affectation is most frequent in the bladder, however,
      we have found less than 100 cases. We present the case of a woman with primary
      amyloidosis of the urinary bladder with symtoms of hematuria. Endoscopic
      examination suggested a bladder tumor.

PMID- 11534411
TI  - [Fetal development and postnatal maturation of the longus colli muscle].
AB  - In adults, the predominant expression of a slow phenotype in the m. longus colli
      corresponds to its important postural function. Morphologically, there is a
      dispersion in fiber size predominating on the fast type 2 fibers which are
      significantly smaller than the slow type 1 fibers. We deemed it of interest,
      therefore, to analyze the metabolic differentiation of the muscle longus colli
      during its development. This study has been carried out on six anatomical
      samples, in foetuses aged between 16 and 40 weeks of pregnancy and in an 18 month
      old child. The histological study combined H&E staining and immunohistochemical
      techniques (using antibodies specific for the slow and the fast isoforms of the
      myosin heavy chains). Our results indicate that the m. longus colli
      differentiates during the foetal period in a way which is quite comparable to
      that of other skeletal muscles, such as the quadriceps. In this series, a major
      slow predominance with a significant dispersion in fiber size was first observed
      in the 18 month-old child. Thus, it can be concluded that the establishment of
      the adult phenotype of this muscle starts during postnatal life, following the
      development of the mechanisms holding up the head and neck and leading to the
      appearance of the cervical lordosis.

PMID- 11534412
TI  - [Arterial anatomy of the facial nerve at the stylo-mastoid foramen].
AB  - OBJECTIVE: To provide specific informations about the arterial related anatomy of
      the trunk of the facial nerve from the stylomastoid foramen to its bifurcation.
      METHODS: Dissection of 30 facial nerves in fresh cadavers after arterial casting
      with red-colored latex. RESULTS: A great anatomic variability does exist. The
      facial nerve is most often in relation to the stylomastoid artery which arises
      from the posterior auricular artery. The stylomastoid artery originates sometimes
      from the occipital artery or from the external carotid artery. In 19 cases of 30
      the stylomastoid artery passes medially to the nerve, and 11 cases laterally.
      CONCLUSION: During parotid surgery, the main trunk of the facial nerve may be
      difficult to identify because of a large-caliber stylomastoid artery which can
      mask it. Therefore it is preferable to dissect this artery with caution,
      remaining at distance from the dangerous.

PMID- 11534413
TI  - A study of variations of transverse foramens of cervical vertebras in human:
      accessory foramina in shape and number.
AB  - Transverse foramens of 250 cervical vertebras were examined. There were accessory
      foramina and variations in shape and number in 10 out of 250 cervical vertebras.
      Since such a variation of foramens, through which the vertebral artery passes,
      has not been detected in the literature, these ten cases are to be considered.

PMID- 11534414
TI  - Origin of the radial and ulnar arteries: variations in 81 arteriograms.
AB  - In a retrospective review of 81 upper extremity arteriograms, 8 (9.8%) origin
      anomalies of the major arteries were detected. High origin of the radial artery
      from the brachial artery was the most frequent variation, found in 7 (8.6%) cases
      representing 87.5% of all variations in this series. In one case, the left ulnar
      artery originated from the axillary artery, accounting for 12.5% of the
      variations. These anomalous origins of the upper extremity arteries can be
      explained on the basis of the embryologic development. It is important for the
      surgeons and radiologists to be aware of the possible arterial variations in
      order to prevent complications during surgical and diagnostic procedures.

PMID- 11534415
TI  - [Relationship between the tendon of the long head of the biceps brachii muscle
      and the glenoid labrum].
AB  - For many authors, the insertion of the long head of the biceps brachii muscle is
      exclusively or mainly located on the supraglenoid tubercle. The aim of this work
      was to study the insertion of the long head of the biceps brachii at macroscopic
      and microscopic examinations. 31 shoulders of macerated cadavers of both sex (age
      range: 52-92 years) were dissected by a posterior approach in order to study the
      glenoid labrum and the origin of the long head of the biceps brachii muscle. At
      macroscopic examination two types of the proximal part of the long head of the
      biceps brachii were demonstrated: a flattened shape in 84% of the cases and a
      hemicylindrical shape in 16% of the cases. Four types of origin were demonstrated
      at dissection: in 64.5% of the cases the tendon inserted mainly on the postero
      superior part of the labrum, in 19.4% of the cases the tendon inserted both on
      the postero-superior and postero-anterior labrum, in 6.4% of the cases it
      inserted only on the supraglenoid tubercle and in three cases the tendon inserted
      on the intertubercular groove. The histologic examination performed on 6 superior
      part of the bicipitolabral complex have all shown that the tendinous fibers
      blended with the glenoid labrum. The examination performed on an complete labrum
      demonstrated tendinous fibers within the glenoid labrum up to the junction
      between the postero-superior and postero-inferior part of the labrum.

PMID- 11534416
TI  - [Metabolic differentiation of the human longus colli muscle].
AB  - The cervical muscles have a dual postural and dynamic function, in order to
      ensure both the stability and the motility of the cervical spine. The functional
      duality together with the complexity of the cervico-cephalic system render the
      study of the cervical muscles difficult, and their physiology is not fully
      understood in humans. This study has been carried out on ten samples from the m.
      longus colli, taken during a surgical procedure in patients aged between 36 to 62
      years. The histological study combined enzyme histochemical (ATPases) and
      immunohistochemical techniques (using antibodies specific for the slow and the
      fast isoforms of the myosin heavy chains). Our results indicate that, in all
      cases, the m. longus colli is composed of muscle fibers with peripheral nuclei
      and with a relative dispersion in size. Histochemically, the type 1 and type 2
      fibers express exclusively either the slow or the fast myosin heavy chain. From a
      quantitative point of view, the proportion of the slow fibers varies between
      extreme values of 30 and 73%; in addition, the dispersion in fiber size
      predominates on the fast type 2 fibers which are smaller than the slow type 1
      fibers. Thus, most of the muscles that we have studied have histologically a slow
      predominance. This predominant expression of a slow phenotype in the m. longus
      colli corresponds to its important postural function, in addition to its phasic
      role during the flexion of the cervical spine.

PMID- 11534417
TI  - [Predicting factors in the efficacy of interferon treatment in chronic hepatitis
      C].

PMID- 11534418
TI  - [The histological lesions of chronic hepatitis C as predicting factors of
      sustained response to the treatment with interferon].
AB  - BACKGROUND: Although many studies have been implemented in order to determine the
      pre-treatment factors that can predict patients' response to interferon (IFN)
      therapy, it is not yet clear whether characteristic histologic abnormalities in
      chronic hepatitis C can predict such response. AIMS: The aim of this study were
      to evaluate, in patients with chronic hepatitis C, (i) the predictive value of
      histologic lesions for the sustained response to IFN therapy (ii) other pre
      treatment (epidemiological and analytical) factors known to be predictive of
      response. PATIENTS AND METHODS: Sustained response was retrospectively evaluated
      in two hundred one patients who had been treated with IFN for at least 3 months
      in four different hospitals from Castilla y Leon. The following histological
      parameters were studied as predictors of response: histological diagnosis,
      Knodell index, grading and stage, characteristic histologic lesions of HCV
      infection. Epidemiological and analytical parameters were also evaluated.
      RESULTS: The rate of patient's sustained response to IFN treatment was 16%. None
      of the histological parameters was useful to predict this response. By univariate
      analysis, age, disease evolution time, mode of viral transmission, GGT, ferritin
      and viral genotype were associated with a sustained response. The most powerful,
      and only independent predictive factor, however, was the genotype (the response
      odds ratio was 8.6). CONCLUSIONS: Histological parameters do not predict the
      response to IFN treatment. Other factors (mainly the viral genotype) are
      associated with a higher response percentage, although no one is useful to decide
      which patients are going to respond.

PMID- 11534419
TI  - [Upper digestive tract findings in elderly patients with iron-deficiency anemia.
      A comparison between users and non-users of non-steroidal anti-inflammatory
      drugs].
AB  - BACKGROUND: Iron-deficiency anemia is common in the elderly. Chronic upper
      gastrointestinal bleeding is its most frequent cause. The use of non-steroidal
      antinflammatory drugs (NSAID) is common in older people. Gastrointestinal
      complications of NSAID may be also more frequent among the elderly. AIMS: The
      study was aimed to evaluate if a history of regular NSAID use in elderly patients
      with iron-deficiency anemia is associated to characteristic findings on
      esophagogastroduodenoscopy. MATERIALS AND METHODS: A total of 91 patients (40% of
      males and 60% females) older than 65 years (mean age 77 years, range 65-90 years)
      entered the study. All of them had been admitted to our Hospital for study of
      iron-deficiency anemia. Thirty-eight patients were regular users of NSAID.
      Esophagogastroduodenoscopy was performed in all patients. RESULTS: The
      prevalences of peptic ulcer, erosive gastritis/duodenitis, and esophagitis were
      similar in NSAID users and non-users (13 vs 11%, 18 vs 15%, and 26 vs 26%,
      respectively). A trend to a higher prevalence of gastric adenocarcinoma was
      observed the group of NSAID non-users (8% vs 23%, p = 0.05).
      Esophagogastroduodenoscopy was entirely normal in 39% of NSAID users and 34% of
      NSAID non-users. CONCLUSIONS: Upper gastrointestinal lesions in elderly patients
      with iron-deficiency anemia are similar in NSAID users and non-users, with the
      exception of gastric adenocarcinoma which can be more common in NSAID non-users.

PMID- 11534420
TI  - [Comparative study of the eradication of Helicobacter pylori: ranitidine bismuth
      citrate versus omeprazole plus two antibiotics for seven days].
AB  - AIMS: To compare the efficacy of ranitidine bismuth citrate (RB) combined with
      two antibiotics during seven days in comparison with OCA-7 for treatment of
      Helicobacter pylori. METHODS: In a randomized clinical trial 200, consecutive
      patients infected by Helicobacter pylori were studied prospectively. One of two
      regimens was given for 7 days; OCA-7 (omeprazole 20 mg b.i.d., amoxycillin 1 gr
      b.i.d., clarithromycin 500 mg b.i.d.) or RBCA (RB 400 b.i.d., amoxicillin 1 gr
      b.i.d., clarithromycin 500 mg b.i.d.). Eradication was defined as a negative
      breath test one month after therapy. RESULTS: 112 male and 88 female with a mean
      age of 48 years (range 18-82). 100 patients were randomized to OCA-7 and 100
      patients to RBCA-7. Overall 186 patients completed the treatment. Intention to
      treat eradication was in the group OCA-7 of 72% and 73% in group RBCA-7. Per
      protocol eradication was in the group OCA-7 of 78% and 77% in group RBCA-7 (p =
      0.3). Five patients in the group OCA-7 and nine in the group RBCA-7, had side
      effects, three of these patients did not complete therapy by diarrhea.
      CONCLUSIONS: RB with two antibiotics is as effective and safe as OCA-7 for the
      eradication of Helicobacter pylori.

PMID- 11534421
TI  - [Low molecular weight heparin versus unfractionated heparin in the treatment of
      deep vein thrombosis].
AB  - BACKGROUND: Low-molecular-weight heparin (LMWH) are replacing unfractionated
      heparin (UH) in treatment of deep vein thrombosis (DVP), showing their security
      and effectiveness. METHODS: To demonstrate their security and effectiveness a
      randomized prospective study was realised. It compared UH with LMWH in DP
      treatment, clinically diagnosed and confirmed with eco-Doppler. The study
      included 32 patients (21 males and 11 females); 15 received UH in continuos i.v.
      infusion and 17 sodic dalteparine, with dicumarinic afterwards in every case. The
      patients were followed for one year. RESULTS: There were no differences between
      the two groups of treatment in clinical/radiological effectiveness either in
      short term nor one year follow up. There were no significative differences in
      side effects. CONCLUSION: LMWH are as effective and safe as UH for DVT treatment.
      They also have a more comfortable dosage for the patient, avoiding the i.v.
      infusion and the coagulation test, which allows treatment at home.

PMID- 11534422
TI  - [Superior vena cava syndrome: presentation of six cases].
AB  - Superior vena cava syndrome is a devastating complication of obstructive lesions
      compromising the superior vena cava an its branches. Most cases today are caused
      by malignant tumors. The most frequent are lung carcinoma. The clinical
      presentation is dyspnea, vuvular enlargement, collateral circulation. Imaging
      techniques and histological confirmation are used for diagnosis. Early diagnosis
      and treatment is needed. The following report deals with six patients with
      superior vena cava syndrome. All entered our hospital through Emergency
      Department. The description of the principal symptoms and sings, the early
      diagnosis and the treatment.

PMID- 11534423
TI  - [Pustulosis of Sneddon Wilkinson disease and multiple myeloma].
AB  - A case of subcorneal pustular dermatosis is described, this disease is not very
      common. Its origin remains unknown, there are some data that indicate an
      immunological basis because of its associations to hematological disorders and
      others autoimmune diseases. The diagnosis is based on clinic suspects and the
      histopathological analysis. The differentiation among other dermatosis like
      pustular psoriasis, due to its therapeutic implication and evolution. This
      patient developed an IgA-K myeloma after nine years of evolution, a very common
      finding in this disease. It has not definitive treatment, being corticosteroids
      and sulfonamides more effective. The prognosis depends on the appearance of
      complications and associated processes.

PMID- 11534424
TI  - [Central diabetes insipidus as clinical presentation of a bronchogenic
      adenocarcinoma].
AB  - Metastatic tumors of the pituitary gland are uncommon. The majority of them are
      silent lesions incidentally discovered at autopsy. In contrast, the occurrence of
      symptomatic metastases is exceptional. Here we report the clinical and
      radiological findings of a 45 year-old woman with a metastatic lung
      adenocarcinoma who presented with diabetes insipidus and hypernatremic
      dehydration. There was no previous history of malignancy, and the pituitary
      metastases were responsible for the first manifestation of the disease. Clinical
      presentation, diagnosis and therapeutic management of patients with pituitary
      metastases are reviewed.

PMID- 11534425
TI  - [Endophthalmitis and multiple brain abscess in a patient with endocarditis due to
      Streptococcus agalactiae].
AB  - Endogenous endophthalmitis is a rare disease caused by hematogenic germ spread
      from an internal focus. Infections due to Streptococcus agalactiae are infrequent
      in adults although new cases had been described recently associated to
      inmunodepression. We present a patient with endocarditis due to Streptococcus
      agalactiae, endophthalmitis and multiple brain abscess. We also review the
      literature.

PMID- 11534426
TI  - [Objectives and therapeutic strategy in type 2 diabetes mellitus].
AB  - United Kingdom Prospective Diabetes Study (UKPDS) has demonstrated definitively
      that patients with type 2 diabetes mellitus (DM) benefit from intensive blood
      glucose control, because it diminishes the risk to develop microvascular
      complications. The therapeutic targets in the type 2 DM have been modified in
      order to reduce the risk of these complications. However, aggressive treatment
      may be disastrous for patients with microvascular complications and/or an
      increased risk of hypoglycemic unawareness, and neither it would be advised in
      older patients or with short life expectancy. The available drugs for treatment
      of type 2 DM offer many options for achieving these therapeutic targets, based on
      the need of the individual patient. In this job we review the targets in the
      metabolic control of type 2 DM and their backgrounds, and we describe briefly the
      therapeutic strategy recommended for reaching these targets, with special
      attention to the new oral antidiabetic agents (repaglinide and
      thiazolidinediones).

PMID- 11534427
TI  - [Contents and educational frame in rheumatology. Comments for a better approach
      to the problem].

PMID- 11534428
TI  - [Pleuro-pericardial metastasis in adenocarcinoma of endometrium].

PMID- 11534429
TI  - [Pulmonary thromboembolism and spiral computed tomography].

PMID- 11534430
TI  - [Primary Sjogren's syndrome associated with autoimmune hepatitis].

PMID- 11534431
TI  - [Hemoperitoneum caused by peritoneal leiomyosarcoma].

PMID- 11534432
TI  - [Sporadic hemochromatosis with intense hepatocellular siderosis].

PMID- 11534433
TI  - [Bacterial endocarditis in an adult with ventricular septal defect].

PMID- 11534434
TI  - [Orbital pseudotumor presenting as bilateral palpebral edema].

PMID- 11534435
TI  - [Listeria monocytogenes meningitis in a patient with HIV infection and
      cytomegalovirus infection after colonoscopy].

PMID- 11534436
TI  - [Reflections on internal medicine].

PMID- 11534437
TI  - [Acute pancreatitis caused by erythromycin].

PMID- 11534438
TI  - [Distraction osteogenesis with double internal devices combined with early
      frontal facial advancement for the correction of facial craniosynostosis. Report
      of clinical cases].
AB  - Frontofacial monobloc advancement is a surgical procedure which corrects at the
      same time both frontal and facial retrusions in faciocraniosynostosis. The high
      risk morbidity limited its use to major exorbitism or severe breathing
      impairment. We report the results of a preliminary experience in five children
      with a mean age of 3.8 years. All patients presented with a Crouzon or Pfeiffer
      syndrome. The procedure performed was a frontofacial monobloc osteotomy with
      peroperative mobilization. Two pairs of distractors (Martin-Medizin) were
      implanted. The upper pair of frontal distractors was located behind the
      supraorbital bar. The pair of temporo-zygomatic distractors (a modification of
      the MicroFrance prototypes) was implanted behind the zygomatic bone. In one
      patient a transfacial pin was connected to the anterior part the lower
      distractors, to avoid facial bipartition. Distraction was performed according to
      classical protocols with a 1 mm advancement per day, until sufficient advancement
      was obtained. The correction of exorbitism and facial retrusion was obtained in
      all cases. An open-bite was created by the advancement in two out of the five
      patients. Minor infection occurred in one patient. This combination of
      distractors with frontofacial advancement seemed to increase the efficacy and
      reduce the morbidity. This might lead to a one stage strategy for
      faciocraniosynostosis treatment, even if minor additive procedures will be
      necessary when children get older and that insufficient facial growth still
      reoccurs.

PMID- 11534439
TI  - [Mid-facial distraction without osteotomy with a trans-facial pin. Report of 4
      clinical cases].
AB  - After the publications of Mulhbauer, Raposo do Amaral and mainly the one of Toth
      and Chin, it has been proved that midfacial distraction was an effective
      procedure for the treatment of cranio-facial dysostosis. First attempts to
      distract (in human) the midface without osteotomies has given poor results
      because devices acting on the zygomatic bone had failed to draw forward the
      maxilla through a thin maxillo-zygomatic suture which had been dislocated. With
      the help of a transfacial pin and an external device, we have obtained in four
      patients an important advancement of the maxilla. We report here the surgical
      procedure and preliminary results.

PMID- 11534440
TI  - [Management of maxillary deficiency through distraction osteogenesis. Report of
      14 cases].
AB  - Maxillary protraction using elastics has been used routinely in patients with
      maxillary hypoplasia. Internal devices with bone anchorage allows more control of
      the distracted callus and more predictable results. The use of distraction
      splints with internal distractors simultaneously provides more accuracy in
      maxillary hypoplasia treatment. Three techniques using internal maxillary
      distractors and distraction splints are exposed for treatment of severe or
      partial maxillary hypoplasia. Fourteen patients have been treated from 1996
      january 1 to 2000 june 30: twelve with a severe maxillary hypoplasia, two with a
      partial hypoplasia, among them eight in childhood or adolescence. The functionnal
      and aesthetic results have been satisfactory in all cases. Vertical maxillary
      hypoplasia treated by internal distractors techniques provides better results
      than traditionals inlay grafted Lefort I osteotomies. Segmental distractions can
      also be used in combination with classic orthognatic surgery.

PMID- 11534441
TI  - [Distraction osteogenesis for the premaxillary reconstruction. Report of 3
      cases].
AB  - Reconstructing the premaxillary is well-known for being difficult and usually
      requires a bone implant, in grafts or flaps. This technique has a high morbidity
      rate and its middle or long term results remain uncertain. Thanks to their
      experience and to the results they achieved in mandible and maxillary osteogenic
      distraction, the authors suggest applying the principle of distraction
      osteogenesis to the premaxillary reconstruction. Three patients have been
      treated: first, two hypoplasias of the premaxillary, sequelae of a cleft palate
      and of a former traumatic loss of teeth; secondly one premaxillary defect
      following a gunshot wound. The first two were women, the other one was man, all
      adults. For premaxillary distraction, an intraoral extramucosa device is made-up
      for each individual case before the surgical operation itself and after an
      orthognathic analysis. The surgical operation consists in a classical segmental
      maxillary osteotomy which respects the palatal periosteum, and also in fitting a
      distractor device with transmucosa screws into the palatal bone. In each of the
      three cases, with a follow-up from 24 to four months, the reconstruction of the
      premaxillary by distraction osteogenesis is considered satisfactory and stable as
      regards both bone and soft tissues. This achieves particularly a very good
      expansion of the fibrous mucosa of the palate which makes it possible to re
      insert false teeth, with or without implants into the bone. The principle of
      distraction osteogenesis applied to premaxillary reconstruction has shown, in our
      cases, very good functional and aesthetic results. Yet the techniques we used are
      simple and have a low morbidity rate; secondly the distraction device is easy to
      design and little expansive.

PMID- 11534442
TI  - [The management of anterior transversal mandibular deficiencies by distraction
      osteogenesis. Preliminary results and report of 3 cases].
AB  - During the last ten years, osteodistraction genesis appeared as being a treatment
      of some maxillo-facial transversal deficiencies. A new technique have been
      develop in Lille Maxillo-Facial Department (Pr Ferri, France). This new technique
      is used in cases of mandibular hyposymphysis, which induce most of the time a
      mandibular incisor crowding. This distraction osteogenesis performed after
      sagittal osteotomy of the mandibular symphysis and associated with orthodontic
      treatment is a solution to avoid teeth extractions. Other treatments could be
      used to solve anterior mandibular teeth crowding but they have disadvantages:
      teeth slicing, teeth extraction or orthodontic teeth tilting. This new technique
      is performed with intra oral-device, small enough to be placed under mandibular
      periosteum. Three patients have been treated by this technique, they got a stable
      result. In these three cases, alveolar and basal bone is present. So for us,
      symphysis osteogenesis distraction appears to be an alternative treatments to
      mandibular incisor crowding.

PMID- 11534443
TI  - [Mandibular advancement: osteotomy or distraction osteogenesis? A case report].
AB  - From an experience in osteogenic distraction techniques acquired since 1993 and
      facing a case of retromandible, the authors have tried to define the criteria
      leading them to suggest a distraction rather a classical surgical procedure. The
      selection of the patient is based upon the age, the significance of the
      advancement, the asymmetry of the advancement and the former existence of a
      temporomandibular joint degenerative disease. Monitoring the distraction, in
      particular with per- and post-distraction orthodontics, remains complicated. The
      overcorrection and the reduction of recurrences after advancement using
      distraction remain openly discussed.

PMID- 11534444
TI  - [Mandibular distraction osteogenesis and dental rehabilitation by osseointegrated
      implants. A case report] ].
AB  - The authors report a case of mandibular reconstruction by distraction
      osteogenesis. The patient presented an interrupting mandibular defect secondary
      to a gunshot injury. The distraction osteogenesis permitted the reconstruction of
      the mandible without bone grafts or flaps. The attached gingiva on the alveolar
      ridge was also recreated by the distraction and allowed a dental rehabilitation
      by osseointegrated implants.

PMID- 11534445
TI  - [Vertical alveolar distraction osteogenesis of the posterior edentulous mandible:
      a case report].
AB  - When it is necessary to increase the vertical height of the residual alveolar
      ridge, alveolar distraction osteogenesis has numerous advantages compared to
      other preprosthetic surgical procedures. It is frequently used for this purpose
      in the anterior region because of the obvious accessibility. The authors present
      a clinical case of edentulous posterior mandible, with insufficient vertical
      alveolar bone height, treated by alveolar distraction osteogenesis leading to
      three titanium fixtures. They explain their choice and discuss the preliminary
      results.

PMID- 11534446
TI  - Mandibular angle augmentation with the use of distraction and homologous
      lyophilized cartilage in a case of morphing to Michael Jackson surgery.
AB  - Correction of an ill-defined mandibular angle is not an easy task, whether it is
      requested by the "congenital, orthognathic or cosmetic" patient. Deliberate over
      correction has not been reported to our knowledge. This article presents a
      combination of distraction osteogenesis and lyophilized cartilage used to three
      dimensionally over-augment the mandibular angle of a long-face prognathic patient
      who had the wish to be morphed to Michael Jackson or at least as far as current
      technique and his endogenic features allowed.

PMID- 11534447
TI  - [Costal chondral grafting combined with mandibular distraction osteogenesis. A
      new approach to the correction of the temporomandibular joint ankylosis in an
      adult. A report of a case].
AB  - The authors present a thirty two years old women complaining of a
      temporomandibular joint ankylosis. History revealed a mandibular trauma sustained
      during the early infancy. The patient presented a typical bird face deformity
      with a maximal mouth opening of zero millimiter. Facing the squelettal
      deformation, the authors decide to combine a simultaneous costochondral graft
      with bilateral horizontal branch distraction. Good functional and aesthetic
      results allow the patient to return to a good social integration with no sign of
      recurrence at the medium term follow-up.

PMID- 11534448
TI  - [Reduction gonioplasty for the prominent mandibular angle. Report of 38 cases].
AB  - The one-stage curved osteotomy of the mandibular angle without resection of the
      masseter was used for 38 patients suffering from prominent mandibular angle from
      december 1996 to november 1997 at our department of plastic and cranio-maxillo
      facial surgery. The preoperative strategy and surgical procedure are described.
      These 38 cases had a low rate of complications and usually good cosmetic results.
      Technical refinements that have improved the results are analyzed. At the present
      time the one-stage curved osteotomy of the mandibular angle is a simple and more
      reliable method for the surgical correction of the prominent mandibular angle,
      which is preferred by us to the other techniques: resection of the masseter alone
      or with straight cutting of the mandibular angle, simple straight cutting of the
      mandibular angle, multistaged osteotomy of the mandibular angle.

PMID- 11534449
TI  - [Giant lymphedema of the upper extremity. A case report].
AB  - The giant lymphoedema of upper limb still a difficult therapeutic problem. The
      authors report a case treated as a Charle's operation derived. They underline the
      operation's value. As they are experienced with the third-degree burned patients,
      they insist on the respect of the pre-muscular aponevrosis during the excision
      and how as possible it's better to take the split-thickness skin graft on the
      excised skin. Excision and graft are made during the same operation. They come
      back to the initial medical treatment and to the different surgical treatments.

PMID- 11534450
TI  - [Manpower problems in dentistry].
AB  - In this special issue the historic and future development of the dentist
      population in the Netherlands is outlined. With regard to the current supply of
      demand a picture is given of the regional variation in the supply of dentists.
      The future developments of the dentist population are put into perspective by
      three papers on developments in professional groups neighbouring dental general
      practice: oral hygienists, maxillofacial surgeons and orthodontists. These papers
      are supplemented by a paper on the expectations patients have regarding their
      dentists, both now and in the future. Finally, the consequences of changes in the
      tasks performed by dentists for the academic dental education, are discussed.

PMID- 11534451
TI  - [Composition of the dentist population: past, present, and future].
AB  - In the Netherlands the population of dentists has gone through major changes in
      the past decades. Currently the enrollment capacity for the dental schools is
      increasing again. In this article the consequences of these changes, both in the
      past as well as in the future, for the structure of the Dutch dentist population
      are described. This specifically includes the age structure and the gender
      specific number of dentists in the period 1950-2020. The size and structure of
      the dentist population is translated into labour supply, expressed in hours
      available for patient treatment. The labour supply turns out to be stable during
      the period 2000-2020. As a comparison the size of the Dutch dentate population is
      discussed. The size of this population will increase considerable in the next two
      decades. Eventually factors which might have an impact of the labour supply of
      dentists are discussed.

PMID- 11534452
TI  - [Shortage of dentists as a regional problem].
AB  - This article is about the dental human resource situation at a regional level in
      the Netherlands. Based on data made available by the Dutch Dental Association
      (NMT) and the Central Bureau for Statistics (CBS), the supply of dentists and the
      potential demand for dental health care within 34 NMT-regions is described.
      Supply and demand are related to each other. In order to gain more insight into
      the relationship between the supply of and the demand for dental care some
      dentist/population ratios have been calculated for each region and for various
      segments of the population separately. It appears that these ratios per region
      vary considerably, which makes the dental human resource issue in the
      Netherlands, from a regional point of view, rather diverse.

PMID- 11534453
TI  - [Dental curriculum and team treatment concept].
AB  - The changing oral situation in the Netherlands, the upgrading of the dental
      hygienist training and the introduction of the bachelor and master degree in the
      Dutch higher education system asks for a new dental professional: the oral
      physician. To prepare the oral physician for his role as leader of a dental team
      several changes and new developments are necessary in the existing dental
      curriculum.

PMID- 11534454
TI  - [Oral hygienist with extended competencies].
AB  - The multidisciplinary team approach could be the answer to increase the available
      manpower in oral care in the Netherlands. After additional education the dental
      hygienist within the dental team could provide more extensive preventive care
      including restorative dental treatment. Implications for the future role, the
      future education and for the number of dental hygienists required are presented.

PMID- 11534455
TI  - [Human resource planning in orthodontics].
AB  - Content and background of the Capacity report 2001 for orthodontics in the
      Netherlands are discussed. The final conclusion of this report is that there is a
      yearly need of an input of 12 to 15 residents into postgraduate orthodontic
      programs. At the moment capacity of postgraduate training programs in the
      Netherlands is 4.5 resident yearly. Discussion is focussed on the advantages and
      disadvantages of the model used for the calculated estimations. More research on
      certain aspects of treatment need and demand is necessary. Implementation of the
      outcome will be a complex process for every party in the orthodontic field.

PMID- 11534456
TI  - [Manpower shortage in oral and maxillofacial surgery--a serious problem in the
      Netherlands].
AB  - In the Netherlands there is currently a shortage of oral and maxillofacial
      surgeons. This shortage will increase between 2001 and 2010. It is analyzed that
      early retirement and reduction of working hours are the major factors which
      contribute to the shortage which will cause serious problems till 2010. Solutions
      will focus on increasing training capacity, reduction of training time and on
      various forms of substitution.

PMID- 11534457
TI  - [What does the patient expect from the dentist now and in the future?].
AB  - In 1992 the Consumentenbond investigated which aspects patients consider to be
      important in the dental practice. The most important aspects were hygiene of the
      practice, technical skills of the dentist and the possibility to ask questions to
      the dentist. Internet will be more important in future communication with the
      consumer. At the moment, however, the quality of information from the internet is
      insufficient.

PMID- 11534458
TI  - [Waiting lists].

PMID- 11534459
TI  - Species/variety differences in biochemical composition and nutritional value of
      Indian tribal legumes of the genus Canavalia.
AB  - Seeds of the Indian tribal pulses Canavalia gladiata (red and brown varieties),
      C. ensiformis and C. virosa were analysed for their physical characters,
      proximate composition, minerals, amino acid composition, dietary fibre
      constituents, starch fractions, fatty acid profiles and various antinutritional
      and/or toxic factors. Among the different species/varieties of Canavalia, the
      brown variety of C. gladiata was found to have the highest amount of protein
      (35.0%). The essential amino acid profile of total seed proteins compared
      favourably with the FAO/WHO reference pattern established for pre-school
      children, except for a deficiency of sulphur containing amino acids in both
      varieties of C. gladiata and C. ensiformis, whereas high concentrations of
      cystine and methionine were detected in C. virosa. However, tryptophan in the red
      variety and lysine in the brown variety of C. gladiata seemed to be the second
      most limiting amino acids. Generally, these Canavalia seeds appear to be a good
      source of potassium, phosphorus and calcium. They contain low levels of sodium.
      Even though the samples contained a high proportion of total starch (31.8-36.9%),
      the percentage of digestible starch appeared to be much higher in C. ensiformis
      (70.6%) and C. virosa (71.8%) than in C. gladiata. The seed lipids of all the
      Canavalia samples investigated had a large proportion of unsaturated fatty acids
      (71-78%) with oleic acid as the major one (38.6-47.4%). All samples were rich in
      dietary fibre (17.5-23.6%), most of which was insoluble dietary fibre. The level
      of the toxic amino acid, canavanine, was found to be relatively low (27-42%) in
      C. gladiata and C. ensiformis compared to previous literature reports for the
      same species. The other antinutrients such as phenolics, tannins, condensed
      tannins, saponins, protease inhibitors, alpha-amylase inhibitor and
      haemagglutinating activity were also analysed and reported here. C. ensiformis
      seeds exhibited a relatively high level (69.0%) of in vitro protein digestibility
      compared to the red (67.2%) and brown (65.4%) varieties of C. gladiata and C.
      virosa (62.5%).

PMID- 11534460
TI  - Twin-screw extrusion of cassava starch and isolated soybean protein blends.
AB  - The effects of the extrusion parameters on isolated soybean protein (ISP) and
      cassava starch (CS) blends were studied. Extruded samples were prepared by using
      a ZSK-30 Werner and Pfleiderer twin-screw extruder. The study was carried out
      using Response Surface Methodology. The ISP followed by the moisture content were
      the most important linear variables significantly affecting axial expansion,
      specific volume, water solubility index and colour difference. The radial and
      axial expansion ranged from 2.30 to 3.77 and from 1.02 to 2.62, respectively. The
      highest ISP concentrations in the blends resulted in the highest specific volumes
      of the extrudates. Simultaneous increases of the barrel temperature and ISP level
      increased the water absorption index and lowered the water solubility index of
      the extrudates. Extruded products were softer at higher barrel temperature. The
      greatest difference in colour values was for the blends with the highest ISP
      concentration.

PMID- 11534461
TI  - Chemical, nutritional and sensory properties of bread supplemented with lupin
      seed (Lupinus albus) products.
AB  - Sweet lupin Lupinus albus seed flour (SLSF), two sweet lupin protein isolates
      (SLPI-I and SLPI-II) and sweet lupin seed protein concentrate (SLSPC) were added
      to wheat flour (WF) in an amount of 3, 6, 9 and 12% of wheat flour. The effects
      of lupin products supplementation on physical dough properties were studied using
      a Brabender farinograph. Loaves were prepared from the various blends using the
      straight dough procedure and then evaluated for volume, crust and crumb colour,
      crumb texture, flavour and overall quality. Water absorption, development time
      and dough weakening were significantly (P < 0.05) increased as the lupin product
      levels increased in all doughs; however, dough stability decreased. Lupin
      products could be added to WF up to 9% level (SLPI-I and SLPI-II) and 6% level
      (for other lupin products), without any observed detrimental effect on bread
      sensory properties. No significant (P > 0.05) differences were recorded in loaf
      volume between control and breads containing SLPI-I and II (up to 9% level) and
      SLSPC (up to 3% level). Addition of lupin products increased the content of
      protein and total essential amino acids, especially lysine. The addition also
      improved in-vitro protein digestibility.

PMID- 11534462
TI  - Effect of soaking, germination, autoclaving and cooking on chemical and
      biological value of guar compared with faba bean.
AB  - Raw, soaked, germinated, autoclaved and cooked both of guar and faba bean were
      chemically and biologically evaluated. Crude protein, crude fiber and ash
      contents of guar and faba bean decreased as a result of all treatments with the
      exception of protein content in both germinated guar and faba bean. A slight
      decrease in lipid content was noticed during germination, while there were no
      changes in lipids after soaking, autoclaving and cooking. Protein content of guar
      was higher than of faba bean, and showed higher values for all amino acids than
      faba bean protein except for lysine and tryptophan. Germination caused a slight
      increase in total essential amino acids, while soaking caused a slight decrease
      in both of guar and faba bean. There was a slight decrease in the mineral
      contents by the heat processes with the exception of Mg and Mn for guar and Na,
      Mn for faba bean due to the cooking process. Germinated guar and faba bean showed
      noticeable decrease in Na, K, Cu, Mn and Mg and a slight increase in Fe and Zn
      than the raw materials. Germination was more effective in reducing phytic acid
      than heat treatment, and therefore it improves the nutritional quality of both
      guar and faba bean. Protein efficiency ratio (PER), true digestibility (DT) and
      biological value (BV) were estimated in all treatments under study using rat
      bioassay procedures. Data revealed pronounced improvements of the nutritive value
      as a result of all processes under study especially germination being the most
      effective.

PMID- 11534463
TI  - Starch and protein digestibility of newly released moth bean cultivars: Effect of
      soaking, dehulling, germination and pressure cooking.
AB  - Effect of soaking (12 h), soaking (12 h) dehulling, germination (60 h) and
      pressure cooking on starch and protein digestibility of four varieties of moth
      bean, one Local commonly used by the farmers of the area and three newly released
      high yielding varieties, Jwala, RMO 225 and RMO 257, was studied. The starch
      digestibility of raw unprocessed moth bean cultivars differed significantly (P <
      0.05) from 25.4-28.2 mg maltose released/g flour being the highest and lowest in
      RMO 257 and RMO 225, respectively. The protein digestibility differed
      significantly from 70.3-74.6 per cent among all the unprocessed varieties of moth
      bean. All the processing treatments namely soaking, dehulling, germination and
      pressure cooking brought about appreciable enhancement in protein digestibility
      (1-19%) over the control and starch digestibility (19-115%) of all the four moth
      bean cultivars. However, out of all the processing treatments, germination (60 h)
      of soaked seeds (12 h) was the most effective in bringing about improvement in
      digestibility of starch and protein followed by dehulling and soaking (12 h).

PMID- 11534464
TI  - Microwave roasting of peanuts: Effects on oil characteristics and composition.
AB  - Roasting of peanuts by microwave heating (MWH) for different periods was studied
      in comparison with conventional heating method (CHM). The oils extracted from
      microwave roasted peanuts (MWRP) showed gradual darkening by time of heating.
      Colour indices of the oil samples were calculated to show the effect of heating
      on the oil colour. Chemical characteristics and fatty acid composition of the
      extracted oils were determined. In addition, peroxide value, conjugated dienes
      and trienes were determined. It was found that very low amounts of epoxy and
      conjugated fatty acids as well as fatty acid peroxides were formed as detected by
      GLC, UV spectrophotometry and peroxide value determinations. Freshly extracted
      peanut oils subjected directly to MWH showed increase of formation of conjugated
      trienes. In addition, the MW treatment causes oil darkening and higher colour
      indices were obtained. It was generally concluded that even short period MWH
      accelerates the formation of some undesirable and harmful compounds (e.g.
      oxidation products, transformed pigments ... etc.) during peanut roasting.

PMID- 11534465
TI  - Functional properties of raw and heat processed cashew nut (Anacardium
      occidentale, L.) kernel protein isolates.
AB  - The functional properties viz. solubility, water and oil absorption, emulsifying
      and foaming capacities of the protein isolates prepared from raw and heat
      processed cashew nut kernels were evaluated. Protein solubility vs. pH profile
      showed the isoelectric point at pH 5 for both isolates. The isolate prepared from
      raw cashew nuts showed superior solubility at and above isoelectric point pH. The
      water and oil absorption capacities of the proteins were slightly improved by
      heat treatment of cashew nut kernels. The emulsifying capacity of the isolates
      showed solubility dependent behavior and was better for raw cashew nut protein
      isolate at pH 5 and above. However, heat treated cashew nut protein isolate
      presented better foaming capacity at pH 7 and 8 but both isolates showed
      extremely low foam stability as compared to that of egg albumin.

PMID- 11534466
TI  - Evaluation of chemical and technological characteristics of new lines of Triticum
      turgidum ssp dicoccum.
AB  - Triticum durum ssp dicoccum also called farro in Italy is gaining more and more
      interest from farmer due to its commercial potentiality. In this paper, thirty
      lines F6 of farro obtained by crossing the cvs. Triticum turgidum ssp durum
      Ofanto and Simeto and T. turgidum ssp dicoccum Molise population were studied.
      They were evaluated with special reference to chemical composition and
      technological characteristics in order to select genotypes suitable for the
      production of food commodities. The storage protein composition (High Molecular
      Weight and Low Molecular Weight Glutenin) was also considered by different
      electrophoretic techniques.

PMID- 11534467
TI  - Composite starch-based coatings applied to strawberries (Fragaria ananassa).
AB  - Starch-based coatings were used to the extend storage life of strawberries
      (Fragaria ananassa) stored at 0 degree C and 84.8% relative humidity. Effects of
      coating formulation (including starch type, plasticizer, lipid and antimicrobial
      agent) were analysed with respect to fruit quality. Plasticizer addition was
      necessary for film and coating integrity to avoid pores and cracks. Plasticizer
      presence reduced weight losses and maintained surface colour of fruits.
      Amylomaize coatings showed lower water vapour and gas permeabilities and
      decreased weight losses for longer periods than corn starch ones. Coatings with
      sorbitol showed lower permeabilities than glycerol ones. Coatings with
      antimicrobial agents decreased microbial counts, extending storage life of coated
      fruits by 10 to 14 days in comparison to the control. The addition of 2 g/l
      sunflower oil to the formulations decreased the water vapour permeability of
      starch-based films, maintained the surface colour of coated fruits and controlled
      effectively fruit weight losses during storage. Lipid addition minimized the
      effects of starch and plasticizer types. Composite starch-based coatings showed
      selective gas permeability (CO2 higher than O2) which helps to delay senescence
      of fruits.

PMID- 11534468
TI  - Effect of aronia berry honey syrup used for sweetening jams on their quality.
AB  - The effects of sweetening agents on the quality of low sweetened jams were
      compared with respect to blackcurrant, raspberry, sour cherry, strawberry, and
      bilberry jams. The sweetening agents were sucrose, aronia berry honey syrup, and
      sucrose + honey syrup at a ratio of 1:1. The level of physicochemical indices,
      especially the content of vitamin C and anthocyanins determined directly after
      production and after 3- and 6-month storage, was used as the quality criterion
      for the evaluation of jams. Moreover, after 6-month storage the products were
      subjected to sensorial analysis. According to the accepted method of the
      investigation the produced jams were characterized by a 32-33% content of
      extract. During the production and 6-month storage the content of acids slightly
      and that of pectin considerably (from 26 to 46%) decreased, although the
      consistency of the jams was not affected thereby. In the case of vitamin C, its
      pronounced losses concerned raspberry (62-67% of the initial value), strawberry
      (57-61%), and sour cherry (57-58%), being distinctly smaller in blackcurrant (13
      16%) and bilberry (15-35%) jams. With respect to anthocyanins a similar
      regularity was observed, the losses reaching 49-63% in strawberry jam, 40-56% in
      raspberry, 33-39% in sour cherry, 30-36% in blackcurrant, and 28-36% in
      bilberries. In almost all the products the losses of vitamin C and anthocyanins
      were higher when sweetening agent was aronia berry honey syrup. The organoleptic
      evaluation showed that the addition of aronia berry honey syrup to raspberry and
      strawberry jams slightly spoiled their colour but improved the aroma and taste.
      In the final score the significant differentiation in favour of the addition of
      aronia berry honey syrup concerned only blackcurrant, sour cherry, and bilberry
      jams.

PMID- 11534469
TI  - Double freezing of saithe fillets. Influence on sensory and physical attributes.
AB  - Fillet samples were processed on board of a research vessel from saithe
      (Pollachius virens) in different states of rigor mortis. In addition, headed and
      gutted fish in different states of rigor were frozen and, after ten days of
      frozen storage, the fish were thawed, processed into fillets and refrozen. During
      subsequent frozen storage at -24 degrees C several quality attributes were tested
      using sensory (Quantitative Descriptive Analysis schemes for flavour and texture)
      and physical (Texture Profile Analysis, penetration force, colour measurement)
      methods. The measurements indicated differences in the quality attributes
      depending on refreezing and rigor states. However, it was not possible to clearly
      distinguish between single and double frozen samples. Therefore, it can be stated
      that, at least when using saithe as raw material for processing battered and
      breaded portions, the different methods of preparing the fillet blocks will not
      significantly affect the quality of the final products.

PMID- 11534470
TI  - Nutritional and bacteriological properties of some game duck carcasses.
AB  - The aim of this work was to evaluate the body composition, bacteriological
      quality, proximate composition, amino acids content, total lipids fractionation,
      as well as fatty acids profile in breast and thigh meat (with skin) of males and
      females of two species of game ducks namely: Pintail (Anas acuta) and garganey
      (Anas querquedula). The obtained results are as follows. The live weight of
      pentail and garganey females constituted 59.0 and 86.0% of male's weight in
      pintail and garganey, respectively. The bacteriological quality revealed that the
      mean values of psychrotrophs, enterobacteriaceae, pseudomonas, coliforms,
      streptococci and Staph. aureus were 4.1, 2.8, 1.7, 2.0, 2.5 and 3.1 log 10 n/g of
      pintail breast muscle. The corresponding values in garganey breast muscle was
      3.8, 3.2, 2.0, 3.0, 2.9 and 3.1, respectively. In the thigh of pintail and
      garganey, the results were more or less different. Neither salmonella nor
      Clostridium perfringens could be isolated from examined game duck carcasses.
      Protein content ranged from 19.0 to 23.8%, fat 4.8 to 23.2%, ash 1.0 to 1.4% and
      energy value 580 to 1191 kJ/100 g in pintail meat against 20.8 to 23.3% protein,
      9.3 to 16.1% fat, 1.3 to 1.4% ash and 741 to 952 kJ/100 g in garganey meat.
      Breast meat of pintail recorded high content of iron (5.12 and 6.19 mg/100 g wet
      basis) in males and females, respectively, against 4.22 and 6.14 mg/100 g in
      garganey meat. The essential amino acids content ranged from 34.3 to 38.6 g/100 g
      protein in pintail meat against 36.3 to 38.1 g/100 g protein in garganey meat.
      The total lipids of pintail and garganey were fractionated to seven fractions.
      The major fatty acids in pintail and garganey lipids were oleic, palmitic and
      stearic. Besides, garganey lipids had more unsaturated fatty acids content
      compared with pintail.

PMID- 11534471
TI  - Acceleration of curing period of pastrami manufactured from buffalo meat:
      Chemical and microbiological properties.
AB  - Usually the curing period of meat used for pastrami manufacture is three weeks at
      room temperature. In the present work a trial aimed to accelerate the curing
      period of pastrami (dry cured meat) prepared from buffalo lean round muscles by
      heat treatment (approximately 71 degrees C--internal; for partial drying) was
      carried out to investigate the probable changes during processing and in quality
      parameters of the end product. Results showed that pH value and the residual
      NaNO2 content decreased, while lactic acid and conversion in meat pigment
      percentages were increased. The determined data indicated remarkable decrease of
      moisture content during aging and curing periods, while the NaCl content in the
      investigated product was noticeably increased. During pastrami processing soluble
      proteins were decreased; the sarcoplasmic protein fraction denatured more rapidly
      than myofibrillar protein. On the other hand, the non-protein nitrogen and the
      insoluble protein nitrogen were increased gradually during ageing and after the
      heat treatment step. Slight variations in their values were observed during
      ripening of pastrami (complete curing and drying in air at room temperature up to
      6 days). Heat treatment caused apparent decrease in Aerobic Plate Count (APC).
      Salmonella and Coliform bacteria were not detected through meat curing and in the
      end product. The suggested heat-treated pastrami was of good quality and nearly
      similar to the traditional sample.

PMID- 11534472
TI  - Can satiety be measured?
AB  - An energy-controlled study on a Western diet composed of 45% fat, 40%
      carbohydrate and 15% protein by energy was carried out. The study consisted of
      four test phases having a length of 9 days in each case, where 8 healthy free
      living subjects were adjusted to individual energy requirements at maintenance
      level. Between the tests, wash-out phases of 4-5 months were inserted to avoid
      adaptation effects. By using a standard breakfast of constant composition,
      satiety was evaluated by applying the concept of categorical comparison, which
      was based on the common fact, that the perception between two meals is changed
      and usually a set of sensations can be discriminated. These were termed very full
      and full (just after finishing a meal), appetite and hungry (just before the next
      meal). These sensations were used as categories on a categorical scale. The
      evaluation of satiety was performed such that on each day of the four test phases
      the subjects had to select over a period of 4 h every 30 min one category out of
      the four, what corresponded to the individual sensation at that time. This
      procedure was followed by a mathematical treatment of data such that the
      individual judgements were transformed into a numerical system. As a result, the
      time course of satiety was available characterizing the time-dependent change of
      the interoception after consuming the test meal. Using this concept highly
      reliable results were obtained as demonstrated by the comparison of the four test
      series.

PMID- 11534473
TI  - Prevalence of physical activity among South Carolina adults.
AB  - Participating in regular PA is associated with many health benefits. Overall, the
      prevalence of inactivity in South Carolina (33 percent) is among the highest in
      the Southeast and in the US as a nation. While few gender differences exist
      between the proportion of adults who report participation in sufficient PA
      (females 21 percent and males 23 percent), racial and age differences are
      apparent with ethnic minorities and older adults as the least active. The most
      popular PA among all adults is walking. Physicians can play a key role, through
      counseling, to help increase the prevalence of regular PA among those who are
      currently obtaining insufficient amounts of activity to derive optimal health
      benefits.

PMID- 11534474
TI  - Health care provider counseling for physical activity among black and white South
      Carolinians.

PMID- 11534475
TI  - Improving the preparticipation exam process.
AB  - The Preparticipation Exam for too long has been a mandatory yearly athletic exam
      and not the base from which a process of continuous athletic care took place. The
      purpose of this article is not only to introduce improvements in the exam itself
      but to also describe some extensions of the process that allow us to improve
      athletic care in South Carolina. It is hoped that a software scanning program
      will allow compiling of demographic data from individual and group examinations
      and thus support the method of exam preferred by all physicians in our state.
      Standard forms will also facilitate communication within the Athletic Care Unit
      and between physicians involved in athletic care.

PMID- 11534476
TI  - Faith versus death: the problem with medicine's faith factor theology.

PMID- 11534477
TI  - Should religiosity be included in the medical history?

PMID- 11534478
TI  - Political activism: why it is a must for medicine.

PMID- 11534479
TI  - Genes and the two ton truck: the myth of preventive medicine.

PMID- 11534480
TI  - One baby too many.

PMID- 11534481
TI  - Genetic research. Cloning: humans may have it easier.

PMID- 11534482
TI  - Keeper of the stem cells.

PMID- 11534483
TI  - When dating is dangerous.

PMID- 11534484
TI  - The trouble with fat-burner pills.

PMID- 11534485
TI  - Proceedings of the 4th European Conference in Audiology. Oulu, Finland, June 6
      10, 1999.

PMID- 11534486
TI  - Modern doctoring.

PMID- 11534487
TI  - Modern doctoring.

PMID- 11534488
TI  - [Pyeloplasty. Early endoscopic view].

PMID- 11534489
TI  - Torasemide--a unique loop diuretic.

PMID- 11534490
TI  - Simple hypertension guidelines for primary health care.

PMID- 11534491
TI  - Adult attention deficit disorder: brain mechanisms and life outcomes. Proceedings
      of the 17th Annual Conference of the New York Neuropsychology Group. April 20,
      1996.

PMID- 11534492
TI  - Proceedings of the 11th International Conference on X-ray Absorption Fine
      Structure. XAFS XI. Ako, Japan, 26-31 July 2000.

PMID- 11534493
TI  - Molecular Biology of Hematopoiesis and Treatment of Leukemia and Cancer.
      Proceedings of the 13th Symposium. New York, New York, USA. July 14-18, 2000.

PMID- 11534495
TI  - Proceedings of a meeting on Quality Health Care for Women in the United States
      and the United Kingdom. Washington DC, USA. September 21-22, 2000.

PMID- 11534494
TI  - Additional resources for building your career.

PMID- 11534496
TI  - Report on the Third Annual Walker's Cay colloquium on cancer vaccines.

PMID- 11534497
TI  - Meningococcal disease in Europe: epidemiology, mortality, and prevention with
      conjugate vaccines. Report of a European advisory board meeting Vienna, Austria,
      6-8 October, 2000.

PMID- 11534498
TI  - Antineoplastic therapy in children and adolescents--a retrospective analysis.

PMID- 11534500
TI  - Current world literature. Oncology: prostate and renal.

PMID- 11534499
TI  - Sickle-cell anemia: report of a case in a newborn infant.

PMID- 11534501
TI  - Current world literature. Oncology: bladder and testis.

PMID- 11534502
TI  - Society for Matrix Biology meeting, Newcastle-upon Tyne, 10-11 September 2000.
      Cell-cell/cell-matrix interactions in connective tissue.

PMID- 11534503
TI  - Sonographic erosions of the rheumatoid little toe.

PMID- 11534504
TI  - Corticosteroid injection for the treatment of carpal tunnel syndrome.

PMID- 11534505
TI  - Fetal microchimerism in Sjogren's syndrome.

PMID- 11534506
TI  - Rapid improvement of SLE-specific cutaneous lesions by C1q immunoadsorption.

PMID- 11534507
TI  - Development of erythroleukaemia after myelodysplastic syndrome in a patient with
      Wegener's granulomatosis.

PMID- 11534508
TI  - Atrophoderma and juvenile idiopathic arthritis.

PMID- 11534509
TI  - Rheumatoid arthritis associated with ulcerative colitis: a case with severe flare
      of both diseases after delivery.

PMID- 11534510
TI  - Ultrasonography is useful to distinguish between intra- and extra-articular
      disease in pyoderma gangrenosum complicating polyarthritis.

PMID- 11534511
TI  - Are DISH and OPLL genetically related?

PMID- 11534512
TI  - Systemic small sized vessel vasculitis after massive antigen inhalation.

PMID- 11534513
TI  - Non-steroidal anti-inflammatory drugs in the treatment of hyper-IgD syndrome.

PMID- 11534514
TI  - [Celiac disease].

PMID- 11534515
TI  - [Diarrhea with vitamin B12 deficiency].

PMID- 11534516
TI  - New variant Creutzfeldt-Jakob disease presenting with loss of taste and smell.

PMID- 11534517
TI  - Obsessive-compulsive characteristics in patients with writer's cramp.

PMID- 11534518
TI  - Cervical spondylotic myopathy and Kennedy syndrome mimicking amyotrophic lateral
      sclerosis.

PMID- 11534519
TI  - Posturally evoked vomiting without nystagmus in a patient with Arnold-Chiari
      malformation.

PMID- 11534520
TI  - Lunchtime headache.

PMID- 11534521
TI  - Painful stimulation.

PMID- 11534522
TI  - Is it really Alzheimer's disease?

PMID- 11534524
TI  - Inorganic chemists get cooking.

PMID- 11534525
TI  - The basis for immunity, natural or acquired. Natural immunity osteopathically
      developed or safeguarded. 1938.

PMID- 11534526
TI  - Osteopathic treatment of the common cold. 1937.

PMID- 11534527
TI  - Angina pectoris with special reference to its mechanical causes. 1938.

PMID- 11534528
TI  - The osteopathic lesion as the etiological factor in some common surgical
      disorders. 1948.

PMID- 11534529
TI  - Ascorbic acid treatment to reduce residual halogen-based oxidants prior to the
      determination of halogenated disinfection byproducts in potable water.
AB  - Treatment of potable water samples with ascorbic acid has been investigated as a
      means for reducing residual halogen-based oxidants (disinfectants), i.e. HOCl,
      Cl2, Br2 and BrCl, prior to determination of EPA Method 551.1A and 551.1B
      analytes. These disinfection byproducts include certain haloalkanes, haloalkenes,
      haloethanenitriles, haloaldehydes, haloketones and trichloronitromethane. When
      used as a dehalogenating agent immediately before analysis, only one analyte,
      2,2,2-trichloroethanediol (chloral hydrate), is significantly decomposed.
      Ascorbic acid is superior to thiosulfate and sulfite as it does not destroy
      trichloroethanenitrile (trichloroacetonitrile), trichloronitromethane
      (chloropicrin) or dibromoethanenitrile (dibromoacetonitrile). Unlike ammonia or
      amines, it is not nucleophilic and cannot form hemiaminals (carbinolamines) with
      carboxaldehydes and ketones. Ascorbic acid treatment can rapidly consume (reduce)
      large amounts of active (oxidizing) halogen compounds, producing only inorganic
      halides and dehydroascorbic acid and not additional halogenated organic
      molecules.

PMID- 11534530
TI  - Comparison of two carbon analysis methods for monitoring diesel particulate
      levels in mines.
AB  - Two carbon analysis methods are currently being applied to the occupational
      monitoring of diesel particulate matter. Both methods are based on thermal
      techniques for the determination of organic and elemental carbon. In Germany,
      method ZH 1/120.44 has been published. This method, or a variation of it, is
      being used for compliance measurements in several European countries, and a
      Comite Europeen de Normalization Working Group was formed recently to address the
      establishment of a European measurement standard. In the USA, a 'thermal-optical'
      method has been published as Method 5040 by the National Institute for
      Occupational Safety and Health. As with ZH 1/120.44, organic and elemental carbon
      are determined through temperature and atmosphere control, but different
      instrumentation and analysis conditions are used. Although the two methods are
      similar in principle, they gave statistically different results in a previous
      interlaboratory comparison. Because different instruments and operating
      conditions are used, between-method differences can be expected in some cases.
      Reasonable agreement is expected when the sample contains no other (i.e., non
      diesel) sources of carbonaceous particulate and the organic fraction is
      essentially removed below about 500 degrees C. Airborne particulate samples from
      some mines may meet these criteria. Comparison data on samples from mines are
      important because the methods are being applied in this workplace for
      occupational monitoring and epidemiological studies. In this paper, results of a
      recent comparison on samples collected in a Canadian mine are reported. As seen
      in a previous comparison, there was good agreement between the total carbon
      results found by the two methods, with ZH 1/120.44 giving about 6% less carbon
      than Method 5040. Differences in the organic and elemental carbon results were
      again seen, but they were much smaller than those obtained in the previous
      comparison. The relatively small differences in the split between organic and
      elemental carbon are attributed to the different thermal programs used.

PMID- 11534531
TI  - Beta-blockade treatment in heart failure: the cardiac insufficiency bisoprolol
      study (CIBIS) project. CIBIS Committees and Investigators. Cardiac Insufficiency
      Bisoprolol Study.
AB  - The efficacy of treatment with diuretics and vasodilators in heart failure has
      shown that compensatory mechanisms may induce vicious circles that can
      precipitate the deterioration of congestive heart failure (CHF). By counteracting
      sympathetic stimulation of cardiac beta-receptors, beta-blocking drugs could
      provide some benefit in CHF. Indeed, the sympathetic stimulation enhances
      metabolic costs and could lead to a further deterioration of myocardial fiber
      function. This could be counteracted by beta-blockade. On the contrary, the loss
      of adrenergic responsiveness due to beta-adrenergic downregulation and depletion
      of norepinephrine stores from sympathetic nerves could be responsible for the
      progressive deterioration of cardiac function. Moderate doses of beta-blocking
      agents could restore such a catecholamine sensitivity by upregulation of beta
      receptors and restoration of norepinephrine stores. Results of clinical trials
      with beta-blockade in CHF are so far controversial. Most studies enrolled
      patients with cardiomyopathy and included small numbers of patients or were
      uncontrolled. The CIBIS trial (Cardiac Insufficiency Bisoprolol Study) has been
      launched in Europe to answer the question of the potential benefit on prognosis
      of beta-blockade therapy in heart failure from any etiology, especially ischemic
      CHF. It is a randomized, placebo-controlled, double-blind multicentric trial
      involving two parallel groups of patients (300 in each group) followed over a 2
      year period. Results from the CIBIS trial should provide conclusive information
      concerning the use of beta-blocking therapy in CHF.

PMID- 11534532
TI  - Compendium of position statements, guidelines and consensus statements on
      allergic and immunological diseases.

PMID- 11534533
TI  - Abstracts of the Congress of the European Association of Nuclear Medicine. 25-29
      August 2001, Napoli, Italy.

PMID- 11534534
TI  - Reinforcing effects of nicotine as a function of smoking status.
AB  - The authors compared acute nicotine self-administration among 4 groups varying in
      current or past dependence: dependent smokers, nondependent smokers, ex-smokers
      who had quit at least 1 year ago, and nonsmokers. Nicotine (0 vs. 12 microg/kg/8
      sprays) available by nasal spray was self-administered with a choice procedure.
      Self-administration also was related to participant characteristics (sex, alcohol
      and caffeine intake, sensation-seeking score) and to subjective responses to
      initial nicotine spray exposure. Nicotine self-administration was similar between
      dependent and nondependent smokers but was greater in those groups than in ex
      smokers and nonsmokers, who did not differ from each other. Self-administration
      was unrelated to most other participant characteristics. In nonsmokers, self
      administration was related directly to pleasurable effects but inversely to
      aversive effects. Few effects were related to self-administration in the other
      groups.

PMID- 11534535
TI  - Effects of adolescent nicotine exposure on opioid consumption and neuroendocrine
      responses in adult male and female rats.
AB  - Effects of adolescent nicotine exposure on illicit drug consumption and
      neuroendocrine functioning were examined in adult rats. Nicotine (NIC; 2 doses)
      or saline (SAL) was administered via osmotic minipumps to 30 male and 30 female
      adolescent Wistar rats for 19 days. After NIC/SAL cessation, oral opioid
      consumption was assessed in the home cage for 4 weeks. Plasma corticosterone and
      ACTH were measured at the end of the experiment. Low-NIC male rats consumed more
      fentanyl than did high-NIC male rats; opioid consumption among adult female rats
      was not altered by NIC exposure. Females consumed more fentanyl than did males,
      regardless of NIC history. NIC exposure increased adult corticosterone and ACTH
      levels in a dose-dependent manner. Results suggest important effects of
      adolescent NIC exposure, including altered neuroendocrine status and opioid
      consumption.

PMID- 11534536
TI  - The changing effector pattern of tardive dyskinesia during the course of
      neuroleptic withdrawal.
AB  - Tardive dyskinesia (TD) is a movement disorder that can be expressed at various
      body effector points, including the face, neck, arms, fingers, legs, and torso.
      In this prospective longitudinal study researchers examined whether the effector
      pattern of TD changed during the course of neuroleptic medication withdrawal in
      adults with mental retardation. Results indicated that the effector pattern of TD
      changed over the course of neuroleptic withdrawal. Peak dyskinesia was associated
      with the involvement of more body areas relative to baseline. Although dyskinesia
      decreased at follow-up and fewer body areas showed signs of dyskinesia, there
      were still differences in the effector pattern of dyskinesia relative to baseline
      at periods of 1 to 2 years following neuroleptic withdrawal. These findings
      suggest that TD is a dynamic disorder associated with changes in both severity
      and effector pattern over time.

PMID- 11534538
TI  - Haloperiodol-induced microcatalepsy differs in CD-1, BALB/c, and C57BL/6 mice.
AB  - The degree of arrest of movement (microcatalepsy) induced by haloperidol at doses
      equipotent for operant rate suppression was measured with computerized
      instrumentation. The inbred C57BL/6 mouse strain displayed more susceptibility to
      microcatalepsy than the CD-1 and BALB/c strains. In addition, the C57BL/6 strain
      exhibited a greater degree of sensitization to repeated dosing than did the other
      2 strains. The results were consistent with the C57BL/6 mouse's hypodopaminergic
      profile reported in the literature but were at odds with results reported for
      conventional catalepsy testing. The C57BL/6 mouse may serve as a model for
      genetic vulnerability to extrapyramidal motor side effects and may be useful in
      quantifying the mild extrapyramidal motor side effects of atypical antipsychotic
      drugs.

PMID- 11534537
TI  - Sequential analysis of the effects of naltrexone on the environmental mediation
      of self-injurious behavior.
AB  - Accumulated evidence shows that biology and the environment can mediate self
      injurious behavior (SIB) in persons with mental retardation. Whether
      pharmacological treatment alters the environmental mediation of self-injury is
      unclear. Opioid antagonist effects on sequential dependencies for self-injury
      were studied in the context of experimental single-subject double-blind placebo
      controlled designs. Direct observational data were collected for 4 adult subjects
      in real time on daily rate of SIB and staff interactions. Clinically significant
      reductions (i.e., > or = 33%) in SIB rate were observed for 3 of the 4 subjects.
      For all subjects, the magnitude of the sequential dependency between staff
      behavior and self-injury was significantly greater during treatment with
      naltrexone than during treatment with a placebo. Results are discussed in
      relation to behavioral mechanisms of action regulating medication effects for
      self-injury.

PMID- 11534539
TI  - Risk factors for tardive dyskinesia in a large population of youths and adults.
AB  - This study was designed to identify predisposing factors for tardive dyskinesia
      (TD) in youths and adults within a large, predominantly developmentally disabled
      and mentally ill population. The findings support previously reported risk
      factors for TD, including increasing age, use of anticholinergic medication for
      those over 40 years old, and long duration of neuroleptic exposure for those over
      18 years of age. Higher cumulative levels of "typical" neuroleptic dosage
      decreased the risk for TD for those over 18. Novel findings included the benefit
      of personality disorder in individuals 18 to 40 years old and the strong risk
      factor of profound mental retardation in all age groups. These findings reveal
      further complex interactions to the risk factors for TD.

PMID- 11534540
TI  - Drug-induced reinstatement to heroin and cocaine seeking: a rodent model of
      relapse in polydrug use.
AB  - The authors investigated several features of polydrug use in rats. Heroin and
      cocaine were self-administered following responses on different levers, with only
      1 drug and 1 lever available on alternate days of training. Four doses of each
      drug (heroin: 25, 50, 100, and 200 microg/kg/infusion; cocaine: 0.25, 0.5, 1, and
      2 mg/kg/infusion) were tested, and each rat was exposed to a single dose
      combination. Rats readily developed drug-specific and dose-related responding.
      During extinction, rats displayed a significant bias for responding on the
      cocaine- associated lever. Priming injections of either cocaine (20 mg/kg) or
      heroin (0.25 mg/kg) reinstated responding that was selective for the lever
      previously associated with each drug. These results suggest that in this type of
      polydrug use, drugs have the capacity to activate drug-seeking behavior
      selectively oriented toward stimuli previously associated with their
      administration.

PMID- 11534541
TI  - Ketoconazole suppresses food restriction-induced increases in heroin self
      administration in rats: sex differences.
AB  - The effects of ketoconazole, an inhibitor of corticosterone synthesis, were
      examined during food satiation and food restriction in male and female rats to
      determine whether increases in heroin self-administration prompted by food
      restriction were due to a stress response. Females self-administered more heroin
      infusions than males under both feeding conditions. Food restriction increased
      heroin infusions by an average of 96% for both females and males. Ketoconazole
      suppressed the increase due to food restriction in females but not in males.
      Corticosterone reversed the effect of ketoconazole in a group of 8 females,
      suggesting an interaction between feeding conditions, sex, and the stress
      response in rats.

PMID- 11534543
TI  - Caffeine promotes an ethanol-induced conditioned taste aversion: a dose-dependent
      interaction.
AB  - The present study examined whether caffeine administered within a dose range
      previously shown to promote ethanol drinking would also alter an ethanol-induced
      conditioned taste aversion (CTA). The results revealed a dose-dependent
      interaction between caffeine and ethanol where caffeine (2.5 and 10 mg/kg)
      promoted an ethanol-induced CTA at a low ethanol dose (1.0 g/kg) but had no
      effect in blocking CTA at the higher ethanol dose (1.5 g/kg). These results were
      found to be unrelated to an alteration in ethanol metabolism, as caffeine had no
      effect in altering blood ethanol levels at the doses tested. In agreement with
      the reward comparison hypothesis, the present results suggest that rather than
      attenuate ethanol's "aversive" effects, caffeine may have promoted an ethanol
      induced CTA by increasing the reinforcing efficacy of ethanol.

PMID- 11534542
TI  - Voucher-based reinforcement of opiate plus cocaine abstinence in treatment
      resistant methadone patients: effects of reinforcer magnitude.
AB  - The study tested a voucher-based abstinence reinforcement procedure for reducing
      opiate and cocaine use in a population of treatment-resistant opiate- and cocaine
      abusing methadone patients. Vouchers exchangeable for goods and services were
      contingent on abstinence from both opiates and cocaine. In two conditions,
      participants could earn up to $374 or $3,369 in vouchers for providing opiate-
      and cocaine-free urine samples. Participants received a daily 60-mg dose of
      methadone. The dose was increased in a second phase, and the voucher conditions
      were replicated. Analyses of both phases revealed trends toward greater
      abstinence under the high voucher condition and suggested that higher doses may
      enhance the efficacy of voucher reinforcement. The results show that
      reinforcement for abstinence from 2 drugs simultaneously can be effective even in
      a treatment-resistant population.

PMID- 11534544
TI  - Consumption-related differences in the organization and activation of marijuana
      expectancies in memory.
AB  - Using a methodology that has advanced the study of alcohol expectancies, the
      authors modeled a semantic network of marijuana expectancies stored in memory.
      They used individual-differences scaling, a form of multidimensional scaling, to
      map expectancies into memory network format and preference mapping to model
      likely paths of expectancy activation. Organization and activation of marijuana
      expectancies were found to vary with consumption level. Heavy marijuana consumers
      emphasized a relaxed-agitated dimension and were most likely to activate positive
      expectancies of relaxation, cognitive enhancement, and social facilitation.
      Nonconsumers, however, emphasized a detached-aware dimension and were more likely
      to activate negative expectancies of cognitive impairment and social impediment.
      Future efforts to alter likely activation patterns may be successful in changing
      use patterns.

PMID- 11534545
TI  - Effects of contextual priming on reactions to craving and withdrawal stimuli in
      alcohol-dependent participants.
AB  - The researchers investigated craving for alcohol using a computerized contextual
      priming task involving alcohol-related or alcohol-unrelated words and nonwords
      under 2 priming conditions in 3 groups of alcohol-dependent participants who had
      abstained from alcohol for 3 to 14 days, 15 days to 6 months, or more than 6
      months. Results indicated that participants who had abstained up to 14 days
      reacted more slowly to alcohol-related words that followed sentences describing
      avoidance of withdrawal than did control participants. Furthermore, the first 2
      groups of participants reacted more slowly to alcohol-related words that followed
      craving sentences, compared with neutral words following neutral sentences. The
      results give preliminary support to the withdrawal and craving models of
      addiction rather than models that separate craving and withdrawal in early
      abstinence. Results are discussed in light of current cognitive approaches to
      alcohol dependence.

PMID- 11534546
TI  - Five cases of microphthalmia with other ocular malformations.
AB  - We report five cases of complex microphthalmia with other ocular malformations in
      infants or children, which were evaluated to investigate the relationship between
      the corneal diameters and total axial length. The size of the globe was measured
      by using computerized tomographic scans (CT scan), A-scan ultrasonography, or
      magnetic resonance imaging (MRI). There is a limited range of well-described
      malformation, including anterior or posterior segment dysgenesis or combined
      pathology such as corneal opacity, small cornea, iris hypoplasia, lens
      dislocation, cataract, chorioretinal coloboma, persistent hyperplastic primary
      vitreous (PHPV), retinal dysplasia, and intraocular tumor. Corneal diameters were
      correlated significantly with total axial length (r2 = 0.88) and decreased
      linearly as the total axial length decreased in these cases. However, there was
      no relationship seen between the total axial length and posterior segment length
      (r2 = -0.06). The results of this study may aid the clinical ophthalmologist to
      accurately understand or assess microphthamia combined with other ocular
      malformations.

PMID- 11534547
TI  - Suppression of platelet-activating factor generation and modulation of
      arachidonate metabolism by dietary enrichment with (n-9) eicosatrienoic acid or
      docosahexaenoic acid in mouse peritoneal cells.
AB  - Several studies have shown that dietary n-3 polyunsaturated fatty acids (PUFAs)
      suppress platelet-activating factor (PAF) generation in leukocytes of humans and
      rodents, which is associated with the antagonism of arachidonic acid metabolism.
      Dietary eicosatrienoic acid (20:3n-9, ETrA) is also suggested to antagonize
      arachidonic acid (AA) metabolism, but its effect on PAF generation in leukocytes
      has not been defined. In the present study, we investigated the effects of an
      ETrA-rich diet on PAF generation and AA metabolism in mouse peritoneal cells,
      which were compared with those of a docosahexaenoic acid (DHA)-rich diet. Mice
      were fed a diet supplemented with a lipid preparation rich in ETrA, a DHA-rich
      fish oil (FO) or palm oil (PO) for 3 weeks, and peritoneal cells containing more
      than 80% of monocytes/macrophages were obtained. The peritoneal cells in the DHA
      and ETrA diet groups generated upon zymosan stimulation a smaller amount of PAF
      than cells in the PO diet group. In the peritoneal cells of the DHA diet group,
      AA contents in phosphatidylcholine (PC) and phosphatidylethanolamine (PE) were
      significantly lower than those in cells of the PO diet group, but those in
      phosphatidylinositol (PI) were not significantly different between the two
      dietary groups. A considerable amount of ETrA was incorporated into the
      peritoneal cells of the ETrA diet group, and AA was reduced as compared with the
      PO diet group. These changes occurred preferentially in PI but to a less extent
      in PC and PE. The amount of free AA released by the peritoneal cells upon zymosan
      stimulation was significantly reduced in the DHA diet group as compared with that
      in the PO diet group, whereas AA release was similar between the PO and ETrA diet
      groups. In conclusion, the effects of dietary ETrA on AA content in the
      phospholipid subclasses and AA release were quite different from those of dietary
      DHA, although both diets suppressed PAF generation in mouse peritoneal cells to a
      similar extent.

PMID- 11534548
TI  - A comparison of the Celera and Ensembl predicted gene sets reveals little overlap
      in novel genes.

PMID- 11534549
TI  - Stem cell differentiation, genetic reprogramming and programmed cell death.
      Abstracts from an international conference of molecular and tumor biology.
      September 2-7, 2001, Santorini, Greece.

PMID- 11534550
TI  - Abstracts of the American Physiological Society Conferences. Cellular and
      Molecular Physiology of Sodium-Calcium Exchange, Banff, Alberta, Canada, October
      10-14, 2001. Genome and Hormones: An Integrative Approach to Gender Differences
      in Physiology, Pittsburgh, Pennsylvania, USA, October 17-20, 2001.

PMID- 11534551
TI  - NATO Advanced research workshop: Endocrine disrupters and carcinogenic risk
      assessment. May 8-12, 2001, Bialystok, Poland. Abstracts.

PMID- 11534552
TI  - International Society for Cardiovascular Surgery 25th International Congress.
      September 9-13, 2001, Cancun, Mexico. Abstracts.

PMID- 11534553
TI  - Abstracts from the Society for Cardiovascular Magnetic Resonance 3rd Annual
      Scientific Sessions. Atlanta, Georgia, USA. January 21-23, 2000.

PMID- 11534554
TI  - Emended description of Buttiauxella agrestis with recognition of six new species
      of Buttiauxella and two new species of Kluyvera: Buttiauxella ferragutiae sp.
      nov., Buttiauxella gaviniae sp. nov., Buttiauxella brennerae sp. nov.,
      Buttiauxella izardii sp. nov., Buttiauxella noackiae sp. nov., Buttiauxella
      warmboldiae sp. nov., Kluyvera cochleae sp. nov., and Kluyvera georgiana sp. nov.
AB  - A total of 219 strains belonging to the genera Buttiauxella and Kluyvera were
      studied; 171 of these strains were isolated from mollusks, mainly snails and
      slugs, obtained from around the world. On the basis of DNA-DNA hybridization
      data, the strains were grouped into 11 genomospecies. A total of 44 phenotypic
      characters were used to differentiate the genera Buttiauxella and Kluyvera at the
      genus level and to identify genomospecies. There were significantly higher
      phenotypic probability distances between the genomospecies in the genus
      Battiauxella and the genomospecies in the genus Kluyvera than between the
      genomospecies in the same genus. Therefore, the existence of Buttiauxella and
      Kluyvera as different genera was confirmed. The existence of new species
      necessitated broadening the definitions of both genera. In two cases,
      Buttiauxella species could not be quantitatively differentiated biochemically,
      and several other pairs of species could be separated only by the results of one
      biochemical test. Nonetheless, combinations of several characteristics were used
      in differentiate all of the species with levels of certainly ranging from log
      10.79 to log 57.77 (calculated as probability distances). The following new
      species are proposed: Buttiauxella ferragutiae (type strain, ATCC 51602 [DSM
      9390]), Buttiauxella gaviniae (type strain, ATCC 51604 [DSM 9393]), Buttiauxella
      brennerae (type strain, ATCC 51605 [DSM 9396]), Buttiauxella izardii (type
      strain, ATCC 51606 [DSM 9397]), Buttiauxella noackiae (type strain, ATCC 51607
      [DSM 9401]), Buttiauxella warmboldiae (type strain, ATCC 51608 [DSM 9404]),
      Kluyvera cochleae (type strain, ATCC 51609 [DSM 9406]), and Kluyvera georgiana
      (type strain, ATCC 51603 [DSM 9409]).

PMID- 11534555
TI  - Why indirect calorimetry in critically ill patients: what do we want to measure?

PMID- 11534556
TI  - Is there a place for prostacyclin in the treatment of septic shock?

PMID- 11534557
TI  - Improving survival in trauma patients with acute respiratory distress syndrome.

PMID- 11534558
TI  - Respiratory distress syndrome in the newborn: role of oxidative stress.
AB  - Reactive oxygen and nitrogen species are generated by several inflammatory and
      structural cells of the airways. These oxidant species have important effects on
      a variety of lung cells as regulators of signal transduction, activators of key
      transcription factors and modulators of gene expression and apoptosis. Thus,
      increased oxidative stress accompanied by reduced endogenous antioxidant defenses
      may play a role in the pathogenesis of a number of inflammatory pulmonary
      diseases, including respiratory distress syndrome (RDS) in the newborn. There
      obviously are conflicting reports on the effect of oxygen, ventilation and nitric
      oxide (NO) on RDS and, thus, the question arises as what the neonatologist should
      do when confronted with a newborn with RDS. Clearly, utilizing lung protective
      strategies requires compromises between gas exchange goals and potential
      toxicities associated with over-distension, derecruitment of lung units and high
      oxygen concentrations. The results discussed in this brief review suggest
      rigorous clinical tests with antioxidants which may help to define the mechanisms
      associated with RDS and which could lead to new treatment strategies.

PMID- 11534559
TI  - The sick euthyroid syndrome in paediatric cardiac surgery patients.

PMID- 11534560
TI  - Acute respiratory distress syndrome among trauma patients: trends in ICU
      mortality, risk factors, complications and resource utilization.
AB  - OBJECTIVE: To evaluate trends in mortality and related factors among trauma
      patients who developed acute respiratory distress syndrome (ARDS). STUDY:
      Observational study based on data prospectively gathered in computerized trauma
      registry. SETTING: Trauma intensive care unit (ICU) of 48 beds in level I trauma
      center. PATIENTS: All trauma patients with ARDS admitted during 1985-87 (486,
      group 1 [G1]) and 1993-95 (552, group 2[G2]). METHODS: ARDS was defined by
      American-European Consensus Conference criteria and the need for 48 h or more on
      mechanical ventilation with FIO2 greater than 0.50 and PEEP of more than 5 cmH2O.
      Demographics, severity score, injury-admission delay time, first 24-h transfusion
      and septic and organ system failure complications were independent variables. ICU
      mortality was the dependent variable. ICU length of stay (LOS) and life support
      techniques were considered. Respiratory and renal support strategies were
      different in the two time periods. RESULTS: Mortality decreased over the period
      (G1: 29.2% vs G2: 21.4%, p < 0.04), in patients aged both over and under 65
      years. Multivariate analysis showed mortality was related to age, severity and
      time period (G1 1.68-fold that in G2) and that the greater G1 mortality was
      related to more renal failure and hematologic failure/dysfunction. ICU LOS
      decreased from 31.7+/-26.7 days (G1) to 27.3+/-22 days (G2) (p < 0.003).
      CONCLUSIONS: Mortality among trauma patients with ARDS declined over the 8 years
      studied and was associated with less organ failure. This reduction was probably
      the result of new approaches to mechanical ventilation, renal failure replacement
      and vasoactive drug therapy.

PMID- 11534561
TI  - Mechanical ventilation in patients with acute ischemic stroke: survival and
      outcome at one year.
AB  - OBJECTIVE: To assess the prognosis of patients with acute ischemic stroke who
      require mechanical ventilation and to determine early factors influencing
      mortality. DESIGN: Prospective observational study. SETTING: Medical intensive
      care unit with a cerebrovascular emergency unit in a university-affiliated
      hospital. PATIENTS: Fifty-eight consecutive patients (mean age 65+/-13 years)
      requiring mechanical ventilation in the early course of an acute ischemic stroke.
      MEASUREMENTS AND RESULTS: Clinical data were recorded before intubation according
      to a standardized procedure. Mortality and functional outcome were assessed after
      a 1-year follow-up. Mechanical ventilation was started within 48 h after
      admission in 53 patients (91.4%). The mean duration of ventilation was similar in
      survivors (9.7+/-9.0 days) and non-survivors (8.6+/-8.7 days). Mortality was
      72.4% at 1 year. Among the 16 survivors, none were in a persistent vegetative
      state and 11 had a Barthel index of 60, reflecting good functional status.
      Bilateral absence of corneal reflex and bilateral absence of pupillary light
      reflex had a positive predictive value of death of 1 (95% CI 0.78-1.00 and 0.74
      1.00, respectively). After Cox regression analysis, presence of stupor or coma
      (OR 2.6, 95% CI 1.5-5.0), bilateral absence of corneal reflex before intubation
      (OR 3.4, 95% CI 1.4-8.7) and presence of ischemic cardiopathy (OR 2.8, 95% CI 1.4
      5.5) were independent predictors of mortality. CONCLUSIONS: Systematic
      withholding of endotracheal intubation in patients with AIS is not recommended.
      Careful and rigorous neurologic examination, including assessment of brain stem
      reflexes, might help to identify patients with a very high probability of death
      despite mechanical ventilation.

PMID- 11534562
TI  - Acute effects of ventilator settings on respiratory motor output in patients with
      acute lung injury.
AB  - OBJECTIVE: During assisted mechanical ventilation, changes in ventilator settings
      may acutely affect the respiratory motor output via the mechanoreceptor reflex
      feedback system, thus interfering with patient management. This feedback system
      in mechanically ventilated patients with parenchymal lung injury remains largely
      unexplored. To investigate this, the early response of respiratory motor output
      to varying ventilator settings was determined in 13 sedated patients with acute
      lung injury. DESIGN: During assist/control and pressure support (PS) ventilation
      changes in (1) tidal volume (V(T)) at fixed inspiratory flow (V'(I)), (2) V'(I)
      at fixed V(T) and (3) PS level were employed and the response of respiratory
      motor output was followed for two breaths after the change. Respiratory motor
      output was assessed by total pressure generated by the respiratory muscles
      (Pmus), computed from esophageal pressure (Pes). RESULTS: Neural expiratory time
      increased with increasing V(T) and PS, while it remained constant with V'I
      changes. Neural inspiratory time (T(I)n) increased with decreasing V'(I) and PS,
      but was not affected by V(T) changes. None of the changes in ventilator settings
      influenced significantly the rate of rise of Pmus, used as an index of
      respiratory drive. The changes in respiratory timing resulted in significant
      changes in breathing frequency, which increased with decreasing V(T) and PS and
      increasing V'(I). The time integral of Pmus, an index of respiratory effort,
      increased with increasing T(I)n. These acute responses were not related to the
      severity of deterioration of respiratory system mechanics. CONCLUSIONS: We
      conclude that alterations in commonly used ventilator settings induce acute
      changes in respiratory timing, without affecting the respiratory drive. These
      changes, probably mediated via mechanoreceptor reflex feedback, are dependent on
      the type of the alteration in the ventilator settings.

PMID- 11534563
TI  - The development of ventilator-associated pneumonia does not change aspects of
      mechanical ventilation.
AB  - OBJECTIVE: To evaluate whether the development of ventilator-associated pneumonia
      (VAP) is associated with changes in ventilation parameters. DESIGN: Matched case
      control study. SETTING: Mixed intensive care unit of a university hospital.
      PATIENTS: From a large database we selected 33 patients with VAP, diagnosed with
      quantitative cultures of bronchoscopically obtained specimens. In addition, 33
      other mechanically ventilated patients who did not develop VAP were selected
      (controls). Patients with VAP and controls were matched on seven variables
      representing severity of illness: duration of ventilation until matching,
      diagnosis on admission, renal function, liver function, preceding infection,
      preceding surgery and immunosuppressive therapy. Each patient with VAP was
      matched to a single control. Variables regarding type and mode of ventilation and
      interpretation of chest radiographs were not included in the matching procedure.
      MEASUREMENTS AND RESULTS: Characteristics of mechanical ventilation (mode of
      ventilation, tidal volume, expired minute ventilation, peak airway pressures,
      mean airway pressures, level of positive end-expiratory pressure, arterial oxygen
      tension(PaO2)/fractional inspired oxygen (FIO2) ratio), were compared on the day
      of diagnosis of VAP (or matching for controls) and 2 and 4 days before. Although
      there was a significant difference in PaO2/FIO2 ratios between cases and controls
      on the day of diagnosis of VAP, the change in PaO2/FIO2 ratios during the days of
      study were not statistically different between patients developing VAP and
      controls. No significant differences were found for any of the other variables of
      ventilation at any of the three time points studied, nor were there significant
      differences in changes of these parameters within individual patients.
      CONCLUSIONS: Characteristics and parameters of mechanical ventilation are not
      influenced by the development of VAP. It is, therefore, unlikely that these
      variables are useful in the diagnostic work-up of VAP.

PMID- 11534564
TI  - Validity of an abbreviated indirect calorimetry protocol for measurement of
      resting energy expenditure in mechanically ventilated and spontaneously breathing
      critically ill patients.
AB  - OBJECTIVE: To test a short indirect calorimetry protocol with five stable 1-min
      readings (5-min steady state) against the commonly used protocol of 30 1-min
      readings (30-min steady state) in critically ill patients with various modes of
      ventilation. DESIGN: A prospective clinical study. SETTING: A medical ICU of a
      university hospital. SUBJECTS: Forty-six mechanically ventilated patients (group
      A and B), and 16 spontaneously breathing patients (group C). INTERVENTION:
      Indirect calorimetry with the Deltatrac II MBM-200 Metabolic Monitor. RESULTS:
      Mechanically ventilated patients were classified into group A (controlled) and B
      (assisted) depending on the ventilation mode. All patients in group A, but only
      48.8% of those in group B, received some form of analgosedation, and the doses
      were significantly higher in group A. The 30-min steady state test was 100.0%,
      83.7%, and 75.0% successful in group A, B, and C, respectively. The corresponding
      rate for the 5-min steady state test was 100.0%, 81.4%, and 100.0%, respectively.
      The coefficient of determination (r2) for resting energy expenditure between the
      two protocols ranged between 0.972 and 0.994. The time required to collect the 5
      min steady state data was 5.5+/-1.1, 9.9+/-5.7, and 6.5+/-3.3 min for group A, B,
      and C, respectively. CONCLUSION: Indirect calorimetry with 5-min steady state
      test correlated very well with the 30-min steady state test in both mechanically
      ventilated and spontaneously breathing patients. The time required varies
      depending on the mode of ventilation, and it is influenced by the level of
      sedation in mechanically ventilated patients. The abbreviated protocol may be
      more acceptable to spontaneously breathing patients.

PMID- 11534565
TI  - A multicenter, open-label, prospective, randomized, dose-ranging pharmacokinetic
      study of the anti-TNF-alpha antibody afelimomab in patients with sepsis syndrome.
AB  - OBJECTIVE: To investigate the pharmacokinetics and safety of afelimomab, a murine
      antibody fragment against human tumor necrosis factor (TNF)-alpha in patients
      with sepsis. DESIGN: Multicenter, randomized, open-label, placebo-controlled
      phase I/II clinical trial. SETTING: Intensive care units of six academic medical
      centers in the United States. PATIENTS: Forty-eight patients with a clinical
      diagnosis of sepsis who received standard supportive care and antimicrobial
      therapy. INTERVENTIONS: Patients received 0.3, 1.0, or 3.0 mg/kg afelimomab or
      placebo intravenously over 20 min. Three patients in each dose group received
      single doses; the remaining nine patients in each group received multiple (nine)
      doses at 8-h intervals over 72 h. MEASUREMENTS AND MAIN RESULTS: Afelimomab
      appeared safe and well tolerated. Single- and multiple-dose kinetics were
      predictable and dose related. The elimination half-life was 44.7 h. Afelimomab
      treatment resulted in increased serum concentrations of TNF (includes TNF
      antibody complexes) and decreased serum interleukin-6 concentrations, whereas no
      discernible trends were observed in placebo-treated patients. There was no
      significant treatment effect on 28-day mortality as was expected given the small
      number of patients. However, overall mortality was significantly (p = 0.001)
      associated with baseline interleukin-6 concentration. All patients experienced
      adverse events, but the vast majority were considered unrelated to the study drug
      and demonstrated no apparent relationship to afelimomab dose. Although 41% of
      patients developed human anti-murine antibodies, there were no clinical sequelae.
      CONCLUSIONS: Multidose therapy with afelimomab was safe, well tolerated, and had
      predictable linear kinetics. A large randomized trial comparing afelimomab to
      placebo in patients with well defined sepsis has recently been completed.

PMID- 11534566
TI  - Hepato-splanchnic metabolic effects of the stable prostacyclin analogue iloprost
      in patients with septic shock.
AB  - OBJECTIVE: To evaluate the effects of the stable prostacyclin analogue iloprost
      on hepato-splanchnic blood flow, oxygen exchange and metabolism in patients with
      septic shock. DESIGN: Prospective clinical study. SETTING: Intensive care unit in
      a university clinic. PATIENTS: Eleven patients with septic shock requiring
      norepinephrine to maintain mean arterial pressure above 70 mmHg. INTERVENTIONS:
      Iloprost was incrementally infused to increase cardiac index by 15%. MEASUREMENTS
      AND MAIN RESULTS: Splanchnic blood flow (Qspl) was measured using the steady
      state indocyanine-green infusion technique and endogenous glucose production rate
      (EGP) using a stable isotope approach. Systemic and splanchnic oxygen consumption
      (VO2), the hepato-splanchnic uptake rates of the glucose precursors lactate,
      pyruvate, alanine and glutamine, the hepatic venous redox state and gastric
      mucosal-arterial PCO2 gradients were determined. After a baseline measurement,
      iloprost infusion was started. After 90 min all measurements were repeated and a
      third measurement was obtained after another 90 min following iloprost
      withdrawal. Qspl (baseline I: 0.82/0.75-1.08 l x min x m2; iloprost: 0.94/0.88
      1.29 l x min x m2; baseline II: 0.87/0.74-1.09 l x min x m2) and splanchnic
      oxygen delivery (baseline I: 122/103-166 ml x min x m2; iloprost: 134/117-203 ml
      x min x m2; baseline II: 130/98-158 ml x min x m2) significantly increased. While
      systemic VO2 significantly increased (baseline I: 139/131-142 ml x min x m2;
      iloprost: 147/136-164 ml x min x m2; baseline II: 143/133-154 ml x min x m2)
      splanchnic VO2 increased in 9 of 11 patients which, however, did not reach
      statistical significance. EGP significantly decreased (baseline I: 23/16-26
      micromol x kg x min; iloprost: 16/14-21 micromol x kg x min; baseline II: 18/12
      20 micromol x kg x min), whereas all other parameters of energy metabolism
      remained unchanged. CONCLUSION: In patients with septic shock an iloprost-induced
      increase in cardiac index increased splanchnic blood flow and shifted oxygen
      utilization from the energy requiring de novo glucose production rate to other
      oxygen-demanding metabolic pathways.

PMID- 11534567
TI  - Macrophage migration inhibitory factor is a critical mediator of systemic
      inflammatory response syndrome.
AB  - OBJECTIVE: To determine the relations between macrophage migration inhibitory
      factor (MIF), tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN
      gamma), and cortisol in patients with systemic inflammatory response syndrome
      (SIRS) and to determine whether their levels correlate with patient survival.
      DESIGN: Prospective, observational, cohort study. SETTING: General intensive care
      unit in a university hospital. PATIENTS AND PARTICIPANTS: The study included 17
      consecutive patients who met the criteria for SIRS; the patients were classified
      into subgroups, survivors (n = 8) and nonsurvivors (n = 9); eight healthy
      volunteers served as control subjects. INTERVENTIONS: None. MEASUREMENTS AND
      RESULTS: Serum MIF, TNF-alpha, IFN-gamma, and cortisol levels were measured
      serially when the patients were first identified as having SIRS (day 0), and on
      days 1-4. Except for the high tendency of acute respiratory distress syndrome in
      nonsurvivors (44%) compared to survivors (13%), there were no differences in the
      clinical backgrounds of the patients between the two groups. All patients had
      multiple organ dysfunction syndrome. The values of MIF and TNF-alpha in the
      nonsurvivors were significantly more elevated than those cytokines measured in
      the survivors and control subjects. Peak MIF levels significantly correlated with
      peak TNF-alpha levels (r2 = 0.448, P = 0.002), but did not correlate with peak
      levels of cortisol and IFN-gamma. Although the levels of IFN-gamma and cortisol
      showed a marked increase compared to those of the control subjects, we could not
      find differences in these variables between the survivors and the nonsurvivors.
      CONCLUSIONS: High MIF and TNF-alpha levels are closely linked with poor outcome
      in patients with SIRS. MIF and TNF-alpha may act together and have pathogenic
      roles in SIRS.

PMID- 11534568
TI  - Acute renal failure after successful cardiopulmonary resuscitation.
AB  - OBJECTIVE: To assess the frequency and independent predictors of severe acute
      renal failure in patients resuscitated from out-of-hospital ventricular
      fibrillation cardiac arrest. DESIGN: A cohort study with a minimum follow-up of 6
      months. SETTING: Emergency department of a tertiary care 2200-bed university
      hospital. PATIENTS AND PARTICIPANTS: Consecutive adult (> 18 years) patients
      admitted from 1 July 1991 to 31 October 1997 after witnessed ventricular
      fibrillation out-of-hospital cardiac arrest and successful resuscitation.
      MEASUREMENTS AND RESULTS: Acute renal failure was defined as a 25% decrease of
      creatinine clearance within 24 h after admission. Out of 187 eligible patients
      (median age 57 years, 146 male), acute renal failure occurred in 22 patients
      (12%); in 4 patients (18%) renal replacement therapy was performed. Congestive
      heart failure (OR 6.0, 95% CI 1.6-21.7; p = 0.007), history of hypertension (OR
      4.4, 95% CI 1.3-14.7; p = 0.02) and total dose of epinephrine administered (OR
      1.1, 95% CI 1.0-1.2; p = 0.009) were independent predictors of acute renal
      failure. Duration of cardiac arrest, pre-existing impaired renal function and
      blood pressure at admission were not independently associated with renal outcome.
      CONCLUSIONS: Severe progressive acute renal failure after cardiopulmonary
      resuscitation (CPR) is rare. Pre-existing haemodynamics seem to be more important
      for the occurrence of acute renal failure than actual hypoperfusion during
      resuscitation.

PMID- 11534569
TI  - Reduced incidence of radiocontrast-induced nephropathy in ICU patients under
      theophylline prophylaxis: a prospective comparison to series of patients at
      similar risk.
AB  - OBJECTIVE: To investigate whether the adenosine-antagonist theophylline reduces
      the incidence of contrast-induced nephropathy (CIN). DESIGN AND SETTING:
      Prospective, comparison to series of patients at similar risk of CIN in a
      university hospital medical ICU. PATIENTS: 78 ICU patients with at least one risk
      factor for CIN undergoing 150 consecutive contrast examinations. INTERVENTIONS:
      Administration of 200 mg theophylline/70 kg BW intravenously 30 min before that
      of 100 ml or more low-osmolarity contrast medium (CM). MEASUREMENTS AND RESULTS:
      Concentrations of serum creatinine and blood urea nitrogen (BUN), urine volume,
      fluid balance, and the incidence of CIN [increase in creatinine > or =20.5 mg/dl
      (= 44.2 micromol/l) within 48 h] were monitored for 48 h. Despite the large
      number of risk factors (6.8 per patient) including a high dose of CM (169.4 ml),
      impaired renal function (51%), diabetes (38%), aminoglycosides (61%), vancomycin
      (53%), catecholamines (52%), creatinine concentrations were not increased 24 h
      (1.40+/-0.92 mg/dl) or 48 h (1.38+/-0.88 mg/dl) after CM [1.47+/-1.0 mg/dl (=
      130+/-88 micromol/l)] vs. baseline. The fluid balance was not different before
      (+3 ml/h) and after CM (-9 ml/h). The urine volume slightly increased after CM
      and theophylline (184 ml/h vs. 164 ml/h). Only three patients (2%) developed CIN.
      The incidence was significantly lower than that of 14% (78/565) in the control
      series with patients at comparable risk of CIN (p < 0.0001). CONCLUSIONS: Using a
      theophylline prophylaxis the incidence of CIN in patients with increased risk of
      CIN is as low as 2%.

PMID- 11534570
TI  - Immediate prediction of recovery of consciousness after cardiac arrest.
AB  - OBJECTIVE: Short-latency somatosensory evoked potential (SSEP) monitoring has
      been reported to be useful in predicting neurological outcome in patients with
      cardiac arrest and hypoxic-ischemic encephalopathy. To obtain the immediate data
      of SSEP and evaluate the relationship between the presence of cortical activity
      and the recovery of consciousness, SSEP was recorded immediately after return of
      spontaneous circulation. DESIGN AND SETTING: Prospective observational study in
      an intensive care unit of a university general hospital. PATIENTS: The study
      included 30 patients resuscitated from out-of-hospital cardiac arrest.
      INTERVENTIONS: Basic and advanced cardiac life support, and intensive care.
      MEASUREMENTS AND RESULTS: SSEP were recorded between 40 and 170 min (median 65)
      after spontaneous circulation returned. In the initial study all 30 patients
      showed the Erb's point potential and the N11-13 component, while only 12 (40%)
      showed cortical activity. Patients were assessed neurologically for recovery of
      consciousness until 1 month after cardiac arrest. Of 12 these patients 8
      recovered consciousness within 10 days, while all patients without cortical
      activity died without opening their eyes. CONCLUSION: Even immediately following
      resuscitation, absence of cortical activity in SSEP indicates unlikelihood of
      recovering consciousness, while the preservation of such activity suggests that
      consciousness is improved. The result promises further accumulation of patients
      to validate the predictive ability of SSEP in managing postresuscitated patients.

PMID- 11534571
TI  - Brain energy metabolism during controlled reduction of cerebral perfusion
      pressure in severe head injuries.
AB  - OBJECTIVE: To study cerebral biochemical markers with intracerebral microdialysis
      and bedside analysis in patients with severe head injuries treated with a
      controlled reduction of cerebral perfusion pressure (CPP). DESIGN: Prospective
      observational study. SETTING: Neurological intensive care unit in a university
      hospital. PATIENTS: A consecutive series of 48 patients with severe head injuries
      and intracranial pressure (ICP) above 20 mmHg after conventional treatment.
      INTERVENTIONS: Reduction of CPP was attained with i. v. infusion of beta1
      antagonist (metoprolol) and an alpha2-agonist (clonidine). One microdialysis
      catheter was inserted via a burr hole frontally to that used for the
      intraventricular catheter ("better" position). In 27 patients one or more
      catheters were inserted into cerebral cortex surrounding an evacuated focal
      contusion or underlying an evacuated haematoma ("worse" position). Perfusion rate
      was 0.3 microl/min and samples were taken every 30 or 60 min. The levels of
      glucose, pyruvate, lactate, glycerol and glutamate were analysed and displayed
      bedside. RESULTS: After initiation of treatment mean CPP decreased from 73 to 62
      mmHg. During the first 96 h CPP was less than 60 mmHg and less than 50 mmHg
      during 30% and 8% of the time, respectively. The treatment was associated with a
      gradual normalisation of all biochemical markers in the "better" as well as the
      "worse" catheter position. CONCLUSION: The study shows that pharmacological
      decrease in CPP according to the "Lund concept" is associated with a
      normalisation of cerebral metabolism. The study also indicates that intracerebral
      microdialysis can be used for evaluation of new treatment strategies.

PMID- 11534572
TI  - Effect of the 1998 Soccer World Cup tournament on rescue requests.
AB  - OBJECTIVES: We studied whether the Soccer World Cup Tournament in 1998 had an
      impact on the number of distress calls received by an emergency service. METHODS:
      Time series analysis was used retrospectively to study the relative frequency of
      telephone calls to a French emergency dispatching center during the period of the
      World Cup. RESULTS: Between 1 May 1997 and 15 August 1998 a total of 109,139
      calls were recorded. During the period of the World Cup (10 June-12 July 1998)
      there was an overall decrease in rescue requests, distress calls, treatments in a
      mobile intensive care unit, and ambulance runs. There was no significant decrease
      during the French team matches except that between France and Italy. DISCUSSION:
      Rescue requests vary with the occurrence of public events. The decline which we
      discovered affected not the period of specific matches but the duration of the
      entire tournament. These results raise the question of the specificity of
      distress calls to an emergency dispatching center that receives not only medical
      requests but also general questions concerning illnesses.

PMID- 11534573
TI  - Influence of prone position on gastric mucosal-arterial PCO2 gradients.
AB  - OBJECTIVE: To evaluate the effects of mechanical ventilation in the prone
      position on gastric mucosal-arterial PCO2 gradients. DESIGN: Prospective clinical
      study. SETTING: Intensive care unit in a university clinic. PATIENTS: Twenty-five
      patients requiring mechanical ventilation. The physician in charge indicated the
      turning manoeuver for the individual patient. MEASUREMENTS/RESULTS: In addition
      to routine measurements of global hemodynamics and gas exchange we determined: 1)
      intragastric pressure; and 2) gastric mucosal-arterial PCO2 difference. After a
      baseline measurement in the supine position patients were turned to the prone
      position. After 60', 120', a median of 6.5 h (2-10 h) in the prone position, and
      again after 60' in the supine position, all measurements were repeated. Global
      hemodynamics remained unaltered throughout the study. While gastric mucosal
      arterial PCO2 gradients did not change significantly during the first 60 min in
      the prone position, they significantly increased during the following 60 min
      [median/percentile: baseline: 6 (1 to -3); 60': 7 (15-5); 120': 13 (20-8) mmHg].
      The median intragastric pressure was not significantly affected [baseline: 10 (13
      5); 60': 12 (16-8); 120': 11 (13-7) mmHg], but 9 of the 11 patients in whom
      intragastric pressure increased during the first 60 min in the prone position
      also showed significantly increased PCO2 gradients (P < 0.01). CONCLUSION:
      Mechanical ventilation in the prone position may be affiliated with increased
      tonometric gastric mucosal-arterial PCO2 gradients depending on the effect on
      intraabdominal pressure. Measuring intraabdominal pressure and/or gastric mucosal
      PCO2 via a nasogastric tube therefore may help to detect adverse effects of this
      ventilatory strategy.

PMID- 11534574
TI  - Dysfunction of vasomotor reactivity in severe sepsis and septic shock.
AB  - OBJECTIVE: Perfusion abnormalities are an overall phenomenon in severe sepsis and
      septic shock, leading to organ dysfunction. We investigated whether carbon
      dioxide (CO2)-induced vasomotor reactivity (VMR) is impaired in septic patients,
      compared with values obtained outside sepsis. DESIGN: Prospective, clinical
      study. SETTING: Six-bed neurologic critical care unit of a university hospital.
      PATIENTS AND PARTICIPANTS: Eight consecutive patients with severe sepsis and
      septic shock. MEASUREMENTS AND RESULTS: CO2-reactivity was measured during and
      outside a period of severe sepsis or septic shock according to ACCP/SCCM criteria
      by means of transcranial Doppler sonography and near-infrared spectroscopy
      (NIRS). VMR was calculated as the percentage change of cerebral blood flow
      velocity (normalized CO2-reactivity, NCR) and absolute changes in concentration
      of oxygenated hemoglobin, deoxygenated hemoglobin, total hemoglobin (HbO2, Hb,
      HbT) and Hbdiff (difference between HbO2 and Hb) in micromol/l per 1% increase in
      end-tidal CO2 (CR-HbO2, CR-Hb, CR-HbT, CR-Hbdiff). NCR and NIRS-reactivities were
      significantly reduced during severe sepsis and septic shock compared with values
      outside sepsis (mean, SD, Wilcoxon): NCR 11.0 (7.1) versus 30.7 (13.0), p < 0.02;
      CR-HbO2 0.70 (0.61) versus 2.33 (1.11), p < 0.02; CR-Hb -0.17 (0.74) versus -1.42
      (1.28), p < 0.04; CR-HbT 0.53 (0.48) versus 1.05 (0.40), p < 0.03; CR-Hbdiff 0.91
      (1.33) versus 3.75 (2.33), p < 0.02. This indicates a severely disturbed VMR.
      CONCLUSIONS: In the advent of a disturbed cerebral autoregulation, critical drops
      in blood pressure during sepsis are transferred directly into the vascular bed,
      leading to cerebral hypoperfusion. This mechanism might contribute to the
      pathogenesis of septic encephalopathy.

PMID- 11534575
TI  - Recurrent rhabdomyolysis and acute respiratory failure due to carnitine
      palmityltransferase deficiency.

PMID- 11534576
TI  - Occupational acute lung injury due to Alternaria alternata: early stage of
      organic dust toxic syndrome requires no corticosteroids.

PMID- 11534577
TI  - Clinical prediction of fluid responsiveness in acute circulatory failure related
      to sepsis.

PMID- 11534578
TI  - Acute zolpidem overdose leading to coma and respiratory failure.

PMID- 11534579
TI  - Inadvertent extubation during percutaneous dilatational tracheostomy: how to
      replace the tracheal tube easily.

PMID- 11534580
TI  - Dioxin detection based on immunoassay using a polyclonal antibody against octa
      chlorinated dibenzo-p-dioxin (OCDD).
AB  - An enzyme-linked immunosorbent assay (ELISA) using a polyclonal antibody against
      octa-chlorinated dibenzo-p-dioxin (OCDD) is presented. This method is based on a
      competitive reaction between OCDD and OCDD-HRP (horseradish peroxidase) conjugate
      against the antibody, whereby OCDD-HRP is detected colorimetrically at 450 nm.
      The detection limit of OCDD was 0.78 pg mL(-1). Optimizing the reaction
      conditions of the assay, cross reactivities of some dioxins against the antibody
      are discussed.

PMID- 11534581
TI  - Visualization of DNA microarrays by scanning electrochemical microscopy (SECM).
AB  - DNA duplex regions of the spots on a DNA microarray were successfully visualized
      by scanning electrochemical microscopy (SECM) in the electrolyte containing
      ferrocenyl naphthalene diimide as a hybridization indicator.

PMID- 11534582
TI  - Amino acid quantitation in aqueous matrices via trap and release membrane
      introduction mass spectrometry: homocysteine in human plasma.
AB  - Trap and release membrane introduction mass spectrometry (T&R-MIMS) using a
      removable direct insertion membrane probe (DIMP) is employed to determine the
      total homocysteine concentration (tHcy) directly from human plasma after
      derivatization with ethyl chloroformate. The method uses no chromatographic
      separation, is linear, reproducible, and displays limit of quantitation (2 pM)
      sufficiently below the threshold concentration of tHcy in plasma. It also
      combines chemical, membrane, and mass spectrometric discrimination, and can be
      used to determine selected amino acids in human plasma simultaneously. After
      derivatization with ethyl chloroformate, many amino acids in aqueous solution are
      observed to be efficiently detected; hence T&R-MIMS is promising as a simple and
      sensitive technique for simultaneous quantitation of selected amino acids in
      plasma and urine, and in other aqueous matrices.

PMID- 11534583
TI  - A portable pulsed cavity ring-down transmissometer for measurement of the optical
      extinction of the atmospheric aerosol.
AB  - A small portable system is described which is used to directly determine the
      optical extinction of the atmospheric aerosol. The requisite highly sensitive
      measurement of the optical extinction is accomplished simultaneously at two
      wavelengths in the near-infrared (1064 nm) and visible (532 nm), using the pulsed
      cavity ring-down (CRD) approach. The measurement at the two wavelengths can aid
      in separating the scattering and absorption components of the optical extinction.
      Rayleigh equivalent optical extinction of approximately 10 x 10(-6) m(-1) from
      particulate matter in the atmospherically important 0.1-2.5 pm diameter size
      range (fine particle accumulation mode) can be readily observed with short (<5 s)
      integration times. Optical extinction is inversely related to the visual range,
      and so the instrument provides a direct measurement of this particulate-related
      air quality indicator. The instrument can also provide particle size range
      selected multiwavelength optical property measurements, which can be inverted to
      provide valuable information about the extant airborne particulate distribution.

PMID- 11534584
TI  - Selective ultra-trace detection of NO and NO2 in complex gas mixtures using broad
      bandwidth REMPI mass spectrometry.
AB  - In this paper we demonstrate the feasibility of ultra-trace resonance enhanced
      multiphoton ionization (REMPI) detection employing a small broad-bandwidth solid
      state laser system. The results reported here are compared with measurements
      carried out with a conventional excimer pumped dye laser combination. Mass
      selected broad-bandwidth REMPI spectra for the environmentally relevant nitrogen
      oxides NO and NO2 are presented. Tunable broad-bandwidth laser radiation with a
      spectral resolution of > 10 cm(-1) in the wavelength range 560-400 nm was
      employed for the detection of NO2. For NO detection, the range 230-224 nm was
      covered. Laser radiation was generated using an optical parametric oscillator
      pumped by an unseeded Nd:YAG laser. A mobile time-of-flight mass spectrometer
      equipped with an atmospheric pressure laser ionization source allowed for mass
      selective parent ion detection at m/z 30 for NO and m/z 46 for NO2. The limit of
      detection was 10 pptV for NO and 20 pptV for NO2. A selectivity of > 2000 for
      both compounds with respect to N2O5, organic nitrates and NO2 in the case of NO
      is reported. An improved laser system currently under construction is expected to
      provide detection limits below pptv mixing ratios for both nitrogen oxides in a
      20 s integration interval.

PMID- 11534585
TI  - Dynamic two-dimensional fluorescence correlation spectroscopy. Generalized
      correlation and experimental factors.
AB  - Dynamic two-dimensional fluorescence correlation spectroscopy (2D FCS) is
      presented in the general form. Dynamic 2D FCS evaluates the time correlation
      function between two wavelength axes when an external perturbation is applied to
      the sample. It displays the vibronic features with similar time response
      functions in the synchronous correlation spectrum and the features with different
      time responses in the asynchronous correlation spectrum. The correlation analysis
      allows detailed assignments of the vibronic spectra of multicomponent samples.
      The emission-emission 2D FCS has proven to be able to resolve spectra with
      substantial overlaps, of species in equilibrium with each other, and of reacting
      species whose kinetic constants are linked and multiexponential. Similarly, the
      correlation analysis between excitation wavelengths allows the assignment of the
      excitation bands to fluorescent components. When a sinusoidal light source is
      used to excite the sample, the excitation-emission correlation requires the
      collection of only four spectra, two in-phase and two quadrature. The two
      dimensional excitation-emission correlation analysis uncovers the association
      between the excitation and the emission vibronic features, enabling the complete
      assignment of the component spectra. The band associations and spectral
      assignments are facilitated by the two-dimensional phase map that is constructed
      from the synchronous and asynchronous correlation spectra. Spectral resolution
      can be optimized by varying the frequency of excitation and is not influenced by
      the detector phase angle used to collect the spectra. The resolution power of the
      2D FCS is demonstrated with the retrieval of the anthracene emission spectrum
      from a pyrene-anthracene mixture when it contributes only 4% to the total
      fluorescence intensity.

PMID- 11534586
TI  - On-line monitoring of electroosmotic flow for capillary electrophoretic
      separations.
AB  - A recently developed technique for monitoring electroosmotic flow (EOF) in
      capillary electrophoresis by periodic photobleaching of a neutral fluorophore
      added to the running buffer has been further characterized and optimized and then
      applied to monitoring EOF during a typical capillary electrophoresis separation.
      The concentration of neutral fluorophore (rhodamine B) added to the running
      buffer for monitoring EOF has been decreased by one order of magnitude. The rate
      at which EOF can be measured has been increased from 0.2 to 1.0 Hz by decreasing
      the distance between the bleaching beam and the laser-induced fluorescence
      detector from 6.13 to 0.635 mm. The precision of the measured EOF ranges from 0.2
      to 1.8%. Under typical experimental conditions, the dynamic range for flow
      measurements is 0.066 to 0.73 cm s(-1). Experimental factors affecting precision,
      signal-to-noise (S/N) ratio and dynamic range for EOF monitoring have been
      examined. This technique has been applied to measure EOF during a separation of
      phenolic acids with analyte detection by UV/VIS absorbance. The EOF monitoring
      method has been shown not to interfere with UV/VIS absorbance detection of
      analytes.

PMID- 11534587
TI  - Conductivity detection for monitoring mixing reactions in microfluidic devices.
AB  - A conductivity detector was coupled to poly(dimethylsiloxane)-glass capillary
      electrophoresis microchips to monitor microfluidic flow. Electroosmotic flow was
      investigated with both conductivity detection (CD) and the current monitoring
      method. No significant variation was observed between these methods, but CD
      showed a lower relative standard deviation. Gradient mixing experiments were
      employed to investigate the relationship between the electrolyte conductivity and
      the electrolyte concentration. A good linear response of conductivity to
      concentration was obtained for solutions whose difference in concentrations were
      less than 27 mM. The new system holds great promise for precision mixing in
      microfluidic devices using electrically driven flows.

PMID- 11534588
TI  - An integrated electrochemical capillary liquid chromatography-dual microelectrode
      system for bromine based reaction detection.
AB  - Amperometric reaction detection of model peptides containing either a thiol or
      disulfide was successfully achieved with a novel coupled capillary liquid
      chromatography-dual microelectrode system. Detection is facilitated via dual
      platinum wire electrodes fabricated directly on a liquid chromatography capillary
      column. The detection strategy is based on the electrogeneration of bromine at
      the upstream working electrode followed by reduction of the bromine to bromide at
      the downstream working electrode. When bromine reacts with analyte eluting from
      the capillary column, the amount of bromine that reaches the downstream electrode
      decreases. As a result, the current at the downstream electrode will decrease in
      proportion to the amount of analyte eluting from the capillary column.
      Glutathione, glutathione disulfide, alpha-TGF and oxytocin were used to
      characterize the system and to determine system parameters. The feasibility of
      the determination of disulfide containing peptides is demonstrated with
      glutathione disulfide, alpha-TGF and oxytocin.

PMID- 11534589
TI  - Chemiluminescence detection of ATP release from red blood cells upon passage
      through microbore tubing.
AB  - A novel approach for the determination of adenosine triphosphate (ATP) released
      from red blood cells (RBCs) after passage through microbore capillaries is
      described. ATP is often released from RBCs in vessels and has been linked to the
      production of nitric oxide, a known vasodilator. The system described here uses a
      syringe pump to deliver microliter flow rates (5-15 microl min(-1)) of reagent
      and sample through fused silica capillary tubing of varying dimensions (25-75
      microm) to a photomultiplier tube. The released ATP is characterized by the
      detection of chemiluminescent emission from the luciferin-luciferase reaction.
      The amount of ATP released is directly proportional to the number of RBCs
      injected into the system. Results also suggest that the amount of released ATP
      decreases from 6.9 microM to 1.4 microM as the tubing diameter is increased from
      25 microm to 75 microm. An investigation of capillary lengths ranging from 15 to
      35 cm resulted in ATP concentrations of 1.5 microM to 2.4 microM being released.
      Results also indicate that increases in flow rate also induce increased amounts
      of ATP release. These results are consistent with those of previous systems
      attempting to model the physiological release of ATP from red blood cells.

PMID- 11534590
TI  - Diffusion and calibration properties of microdialysis sampling membranes in
      biological media.
AB  - The diffusion and calibration properties for three commercially available
      microdialysis membranes (polycarbonate-polyether (PC), polyacrylonitrile (PAN),
      and cuprophan (CUP)) were evaluated. The analytes studied had molecular weights
      between 94 (phenol) and 1355 (vitamin B12). For each analyte-membrane pair, an
      effective membrane diffusion coefficient was calculated. Effective membrane
      diffusion coefficients varied considerably between the microdialysis membranes.
      For Vitamin B12, CUP and PAN membranes gave relative recovery values of greater
      than 20% at 0.5 microl min(-1), while the PC membrane had a 1% recovery. When
      backpressure was applied. PC and PAN membranes exhibited more ultrafiltration
      than CUP membranes. Ultrafiltration did not affect analyte relative recovery
      through either PC or PAN membranes. Effective membrane diffusion coefficients
      were not significantly altered for some membrane-analyte combinations when
      exposed to 4% bovine serum albumin or 0.3% fibrinogen. These data suggest that
      reductions in relative recovery during long-term microdialysis sampling
      experiments may be due to other physiologically relevant proteins or to tissue
      reactions near the dialysis membrane.

PMID- 11534591
TI  - Spectroscopic analysis of the tribological behavior of a model boundary layer
      lubricant.
AB  - Highly ordered alkanethiol self-assembled monolayers (SAMs) on gold substrates
      are suitable models of boundary layer lubricants and may be used in actual
      nanoscale device applications. Here, such monolayers were studied by
      spectroscopic methods as a function of tribological wear (rubbing) using a pin-on
      disk microtribometer. The coefficient of friction (COF) (ratio of the frictional
      force to the load) was measured with the tribometer, and reflectance infrared
      spectra and X-ray photoelectron spectra were obtained as the monolayer film
      failed and the COF changed. The results show that it is possible to correlate
      disorder in the monolayer film with tribological failure of the film, and that
      continued rubbing produces a chemical change in the monolayer film. Disorder in
      the monolayer is distinct from the influence of wear in the underlying gold
      substrate. Aged SAMs, having sulfonate rather than thiol headgroups and initially
      less well ordered, behave differently to the well-ordered freshly prepared SAMs.
      Interestingly, they show a lower COF over many more cycles of exposure to the
      rubbing pin. The impact of the mechanism of film failure in boundary layer
      lubrication is discussed.

PMID- 11534592
TI  - Biochemically functionalized silica nanoparticles.
AB  - In this report, we demonstrate the biochemical modification of silica based
      nanoparticles. Both pure and dye-doped silica nanoparticles were prepared, and
      their surfaces were modified with enzymes and biocompatible chemical reagents
      that allow them to function as biosensors and biomarkers. The nanoparticles
      produced in this work are uniform in size with a 1.6% relative standard
      deviation. They have a pure silica surface and can thus be modified easily with
      many biomolecules for added biochemical functionality. Specifically, we have
      modified the nanoparticle surfaces with enzyme molecules (glutamate dehydrogenase
      (GDH) and lactate dehydrogenase (LDH)) and a biocompatible reagent for cell
      membrane staining. Experimental results show that the silica nanoparticles are a
      good biocompatible solid support for enzyme immobilization. The immobilized
      enzyme molecules on the nanoparticle surface have shown excellent enzymatic
      activity in their respective enzymatic reactions. The nanoparticle surface
      biochemical functionalization demonstrates the feasibility of using nanoparticles
      for biosensing and biomarking applications.

PMID- 11534593
TI  - Characterization of DNA-protein complexes by capillary electrophoresis-single
      molecule fluorescence correlation spectroscopy.
AB  - A high-speed capillary electrophoresis mobility shift assay (CEMSA) for
      determining the binding ratios of DNA-protein complexes in solution is
      demonstrated. Single molecule fluorescence correlation spectroscopy (FCS) was
      used to resolve the bound and unbound fluorescently labeled DNA molecules as they
      flowed continuously through a fused silica capillary under the influence of an
      applied electric field. Resolution of the bound and unbound complexes was based
      on the difference in their electrophoretic mobilities, and was accomplished
      without the need to perform a chemical separation. Data sufficient to perform the
      analysis was acquired in less than 10 s, compared to the minutes that are
      normally needed to carry out such measurement via CE separation. The binding
      ratios were determined with 5 to 10% precision and agreed with the results
      obtained by CE separation within experimental error. The resolution of the CEMSA
      based FCS analysis (CEMSA-FCS) was significantly higher than for the analysis
      performed by conventional diffusional FCS, due to the higher mass sensitivity of
      the electrophoretic mobility compared to the translational diffusion coefficient.
      Fluorescently labeled 39-mer single stranded DNA (ssDNA) and the single stranded
      binding protein (SSB) from Escherichia coli was used as the model system. The
      dissociation constant of the ssDNA-SSB complex was estimated to be approximately
      2 nM based on the CEMSA-FCS analysis.

PMID- 11534594
TI  - Novel solution-phase immunoassays for molecular analysis of tumor markers.
AB  - at 3 x 10(9) M(-1) and a step-wise binding process with PSA-free MAB. Thus, this
      solution-phase quantitative ECL immunoassay allowed measurement of the affinity
      of serum PSAs with their MABs and screening of PSAs based upon their affinity to
      MABs. Unlike other immunoassays, this immunoassay demonstrated one-step rapid
      analysis while simultaneously eliminating immobilization, separation and washing
      steps and detected PSA at a level of 1.7 pg mL(-1), which is 1000-fold more
      sensitive than current PSA immunoassays. Furthermore, single-molecule (SM)
      phosphorescence microscopy was developed to detect single serum PSA-free and PSA
      complex molecules in solution with no use of antibody showing that PSA-free
      molecules diffused faster than PSA-complex molecules in solution. This finding is
      consistent with ECL measurements and implies the possibility of screening
      individual analytes in a complex mixture using their distinct SM diffusion
      distance. This is the first report describing the detection of single protein
      molecules labeled with a metal-complex using phosphorescence microscopy and also
      the screening of serum tumor markers using ECL and SM phosphorescence solution
      phase assays.

PMID- 11534595
TI  - Embossed polymer leaky waveguide devices for spectroscopic analysis.
AB  - A combination of UV embossing, hot embossing and laminating techniques have been
      exploited during the fabrication of grating-coupled waveguiding devices in which
      the flow channel materials and geometry are designed for the effective support of
      light condenser modes through a sample solution. Used in conjunction with LED
      sources, these devices have been employed as optical platforms to obtain
      fluorescence emission and molecular absorption spectra in aqueous media for
      microTAS (micro total analytical system) applications.

PMID- 11534596
TI  - Preliminary studies of a fast screening method for cocaine and cocaine
      metabolites in urine using hollow fibre membrane solvent microextraction
      (HFMSME).
AB  - A simple and efficient screening method for cocaine and cocaine metabolites has
      been developed using an inexpensive, disposable hollow fibre membrane. Drug
      extraction was achieved using hollow fibre membrane solvent microextraction
      (HFMSME). Extraction and separation, using a gas chromatograph, was achieved in
      less than 7.5 min. Using HFMSME, concentrations below 0.050 microg mL(-1) were
      measurable. Good reproducibility was achieved when an internal standard was used,
      producing relative standard deviation values averaging 5.4%. The effects of
      various adulterants and interferents on the screening technique were studied and
      a direct comparison to drop solvent microextraction was made.

PMID- 11534597
TI  - Metal fractionation in olive oil and urban sewage sludges using the three-stage
      BCR sequential extraction method and microwave single extractions.
AB  - The conventional three-stage BCR sequential extraction method was employed for
      the fractionation of heavy metals in sewage sludge samples from an urban
      wastewater treatment plant and from an olive oil factory. The results obtained
      for Cu, Cr, Ni, Pb and Zn in these samples were compared with those attained by a
      simplified extraction procedure based on microwave single extractions and using
      the same reagents as employed in each individual BCR fraction. The microwave
      operating conditions in the single extractions (heating time and power) were
      optimized for all the metals studied in order to achieve an extraction efficiency
      similar to that of the conventional BCR procedure. The measurement of metals in
      the extracts was carried out by flame atomic absorption spectrometry. The results
      obtained in the first and third fractions by the proposed procedure were, for all
      metals, in good agreement with those obtained using the BCR sequential method.
      Although in the reducible fraction the extraction efficiency of the accelerated
      procedure was inferior to that of the conventional method, the overall metals
      leached by both microwave single and sequential extractions were basically the
      same (recoveries between 90.09 and 103.7%), except for Zn in urban sewage sludges
      where an extraction efficiency of 87% was achieved. Chemometric analysis showed a
      good correlation between the results given by the two extraction methodologies
      compared. The application of the proposed approach to a certified reference
      material (CRM-601) also provided satisfactory results in the first and third
      fractions, as it was observed for the sludge samples analysed.

PMID- 11534598
TI  - Large-volume sample stacking for on-capillary sample enrichment in the
      determination of naphthalene- and benzenesulfonates in real water samples by
      capillary zone electrophoresis.
AB  - We investigated the on-line preconcentration of a test mixture of 15 substituted
      and unsubstituted naphthalene(NSs) and benzenesulfonates (BZSs) by large-volume
      sample stacking (LVSS). Analyses were carried out by capillary zone
      electrophoresis (CZE) with on-column UV detection. In particular, we focused on
      how experimental variables such as the inside diameter of the capillary, the
      volume of sample introduced and polarity switching influenced the enrichment
      procedure. The best results were obtained when 300 nl were injected and stacked
      using a bubble cell capillary. Under these conditions, LVSS increased the
      detector response of conventional hydrodynamic injection by a factor of 40. The
      limits of detection of the method were between 5 and 10 microg l(-1).
      Determinations were reproducible, in terms of peak area and migration time, under
      such conditions. The performance of the method was examined by determining NS and
      BZS in real samples, such as tap, river and surface waters and inflow/outflow
      waters from a water treatment plant. Real samples were injected directly into the
      CZE column with little or no preparation.

PMID- 11534599
TI  - Retention characteristics of porous graphitic carbon in reversed-phase liquid
      chromatography with methanol-water mobile phases.
AB  - The solvation parameter model is used to study the retention mechanism of neutral
      organic compounds on porous graphitic carbon with methanol-water mobile phases
      containing from 0-100% (v/v) methanol. The dominant contribution to retention is
      the cavity formation-dispersion interaction term, composed of favorable
      interactions in the mobile phase (hydrophobic effect) and additional
      contributions from adsorption on the graphite surface. Electron lone pair and
      dipole-type interactions in the adsorbed state result in increased retention.
      Hydrogen-bonding interactions are more favorable in the mobile phase resulting in
      lower retention. The changes in the system constants of the solvation parameter
      model for cavity formation-dispersion interactions and hydrogen-bond interactions
      are linearly related to the volume fraction of water in the mobile phase. The
      system constants for electron lone pair interactions and dipole-type interactions
      are non-linear and go through a maximum and minimum value, respectively, at a
      specific mobile phase composition. The solvation parameter model poorly predicts
      the retention properties of angular molecules. This is probably due to the
      failure of the characteristic volume to correctly model the contact surface area
      for the interaction of angular molecules with the planar graphite surface.
      General factors affecting the quality of model fits for adsorbents are discussed.

PMID- 11534600
TI  - Determination of PAH in food samples by HPLC with fluorimetric detection
      following sonication extraction without sample clean-up.
AB  - A rapid method is proposed for the determination of 16 polycyclic aromatic
      hydrocarbons (PAH) in non-fatty food (mashed potato, potato and toasted bread
      samples) based on their extraction with ethyl ether-methylene chloride (1:1) by
      sonication, and subsequent separation by high-performance liquid chromatography
      (HPLC) with fluorimetric detection. A Hypersil Green PAH column was used with a
      gradient of acetonitrile-water as the mobile phase, together with a programme of
      ten excitation and emission wavelength pairs. At levels 1.60-2320 microg kg(-1),
      mean recoveries of PAH were in the range 70-86% for mashed potato, potato and
      toasted bread samples. The relative standard deviations were in the range 4.2-11%
      (n = 6). Total PAH found in mashed potato were in the range 9.35-17.1 microg kg(
      1), in potato samples 8.47-17.2 microg kg(-1) and in toasted bread samples 7.38
      18.0 microg kg(-1), with relative standard deviations in the range 0.8-12%. Only
      chrysene, determined in Ortiz toasted bread (7.38 microg kg(-1)), has
      carcinogenic properties.

PMID- 11534601
TI  - Development and validation of a method for the determination of sub-additive
      levels of virginiamycin in compound animal feeds by liquid chromatography.
AB  - A method for the detection of virginiamycin M1 as a marker compound of
      virginiamycin at sub-additive level in pig, calf, piglet, sow, poultry, cattle
      and laying hen feeds was developed and validated. Both UV detection at 230 nm and
      MS detection were applied. Virginiamycin M1 was extracted from animal feeds with
      ethyl acetate after wetting of the feed with water followed by clean-up on Sep
      Pak silica gel and OASIS HLB cartridges. Analysis of extracts was carried out on
      an Inertsil ODS-2 column with acetonitrile-water-formic acid as the mobile phase
      and UV detection at 230 nm. The limit of quantification (LOQ) of the method was
      2.7 mg kg(-1). The proposed method was validated at a target species dependent
      minimum required performance limit (MRPL), at 2MRPL and at 5MRPL levels in pig,
      calf, piglet, sow, poultry, cattle and laying hen feeds. Recoveries at target
      species dependent MRPL levels ranged from 38 to 67%, within-day repeatabilities
      from 7 to 19% and within-laboratory reproducibilities from 13 to 27%. The
      proposed UV method is primarily suitable for screening purposes at subadditive
      levels, but semi-quantitative data can also be produced. Three MS detection modes
      (ion-source CID, full MS and MS2) were tested as an alternative and/or extension
      to UV detection. The selectivity and sensitivity of both LC-MS2 and LC-MS were
      much better than those of UV detection at 230 nm.

PMID- 11534602
TI  - Simultaneous determination of morphine and its glucuronides in rat hair and rat
      plasma by reversed-phase liquid chromatography with electrospray ionization mass
      spectrometry.
AB  - The simultaneous determination of morphine and the glucuronide metabolites
      [morphine-3-beta-D-glucuronide (M3G) and morphine-6-beta-D-glucuronide (M6G)] in
      rat hair and rat plasma was carried out using reversed-phase high-performance
      liquid chromatography (HPLC) coupled with electrospray ionization mass
      spectrometry (ESI-MS). The chromatographic separation of the analytes was
      achieved using a semi-micro-HPLC column (3 microm particle size; 100 x 2.0 mm id)
      by gradient elution with 50 mM ammonium acetate and acetonitrile as eluents.
      After separation, morphine and the glucuronides were determined by selected ion
      monitoring (SIM) of ESI-MS using the quasi-molecular ions [M + H]+ at m/z = 286
      and 462, respectively. The calibration curves were linear between the
      concentration of the analytes and the deuterium-labelled morphine (M-d3) selected
      as internal standard. The method was applied for the determination of the
      incorporation of morphine and the glucuronides into the hair shafts and hair
      roots of Dark Agouti rats after single intraperitoneal administration of morphine
      hydrochloride. Plasma concentrations of morphine and glucuronides were
      simultaneously determined after administration. Morphine and M3G were detected in
      the hair shafts and the hair roots. The concentrations of M3G in the hair root
      were lower than those of morphine in all sampling periods. In contrast, M3G
      concentrations in plasma were relatively higher at each sampling time. Small
      quantities of M6G were also identified in the plasma up to 4 h after
      administration. The concentration difference between the hair root and plasma
      seems to be due to the incorporation ratio of morphine and glucuronide into hair.
      As M3G was also identified in the hair shaft 1 week after administration, the
      incorporation of glucuronide metabolites into hair is obvious. This is the first
      report of the identification of morphine glucuronide in hair samples without the
      use of acid hydrolysis or enzyme digestion.

PMID- 11534603
TI  - Potential for the speciation of Zn using fast protein liquid chromatography
      (FPLC) and convective interaction media (CIM) fast monolithic chromatography with
      FAAS and electrospray (ES)-MS-MS detection.
AB  - Analytical procedures were developed for the speciation of Zn using fast protein
      liquid chromatography (FPLC), flame atomic absorption spectrometry (FAAS) and
      convective interaction media (CIM) fast monolithic chromatography with FAAS and
      electrospray (ES)-MS-MS detection. The investigation was performed on synthetic
      solutions (2 microg cm-3 Zn) of hydrated Zn2+ species and Zn complexes with
      citrate, oxalate and EDTA (ligand-to-Zn molar ratio 100:1) over a pH range from
      5.4 to 7.4. It was found that Zn interacts with various buffers and the careful
      adjustment of the pH with diluted solutions of KOH is, therefore, required. FPLC
      separations were carried out on a Mono Q HR 5/5 strong anion-exchange column,
      applying an aqueous 1 mol dm(-3) NH4NO3 linear gradient elution over 15 min, at a
      flow rate of 1.0 cm3 min(-1). The separated Zn species were determined in 1.0 cm3
      eluate fractions "off line" by FAAS. Speciation of Zn was also performed on a
      weak anion-exchange CIM DEAE fast monolithic disc by applying an aqueous 0.4 mol
      dm(-3) NH4NO3 linear gradient elution over 7.5 min, at a flow rate of 2.0 cm3
      min(-1) and determination of the separated Zn species in 1.0 cm3 eluate fractions
      "off line" by FAAS. Zn-binding ligands in separated fractions were also
      characterized by electrospray (ES)-MS-MS analysis. The CIM DEAE disc was found to
      be more efficient in the separation of negatively charged Zn complexes than the
      Mono Q FPLC column. On the CIM DEAE disc Zn-citrate was separated from both Zn
      oxalate and from Zn-EDTA. All these species were also separated from hydrated
      Zn2+, which was eluted with the solvent front. This method has an advantage over
      commonly used analytical techniques for the speciation of Zn which are only able
      to distinguish between labile and strong Zn complexes. Good repeatability of the
      measurements (RSD 2-4%), tested for six parallel determinations (2 microg cm(-3)
      Zn) of Zn-EDTA, Zn-citrate and Zn-oxalate was found at a pH of 6.4 on a CIM DAEA
      disc. The limit of detection (3s) for the separated Zn species was 10 ng cm(-3).
      The proposed analytical procedure was applied to the speciation of Zn in aqueous
      soil extracts and industrial waste water from a lead and zinc mining area.

PMID- 11534604
TI  - Monitoring of 6-chloronicotinic acid in human urine by gas chromatography-tandem
      mass spectrometry as indicator of exposure to the pesticide imidacloprid.
AB  - A new analytical method for determining 6-chloronicotinic acid (6-ClNA) in human
      urine is proposed. 6-ClNA is the main metabolite in warm-blooded animals after
      exposure to the insecticide imidachloprid. 6-ClNA was extracted from human urine
      using solid phase extraction (SPE) with laboratory-made cartridges of Amberlite
      XAD-4. A clean-up step and a derivatization process were carried out prior to gas
      chromatography-tandem mass spectrometric (GC-MS-MS) determination. A study on the
      influence of pH in the extraction process revealed that it affects the analyte
      extraction efficiency. A working pH zone was defined between 0.8 and 2.8.
      Calibration curves were studied in the concentration range of 0.5-100 ng mL(-1)
      and showed good linearity. Limits of detection and determination of the method
      were 16 and 56 pg mL(-1) respectively. The mean recovery at 10 and 100 ng mL(-1)
      was between 97.2 and 102.1% and the repeatability was lower than 5.4% in all
      cases. The analysis of urine samples of five agricultural workers from Almeria
      (Spain) did not detect the metabolite.

PMID- 11534605
TI  - Electrospray ionisation-mass spectrometry of hydroxamate siderophores.
AB  - Electrospray ionisation-mass spectrometry (ESI-MS) was applied to the detection
      of the iron complexes of the hydroxamate type siderophores ferrioxamine (FO),
      ferrichrome (FC) and iron(III) rhodotoluate (FR). Mass spectra of the three
      siderophores produced by ESI-MS were dominated by the protonated (M + 1)+ parent
      ions, except for FR at pH 4.3, which was present as the positively charged 1:1
      complex. On collision with He ions, fragmentation proceeded largely via cleavage
      of C-N bonds. Flow injection analysis of the siderophores with detection by ESI
      MS produced detection limits of 1.9 fmol for FO, 31.1 fmol for FC and 524 fmol
      for FR.

PMID- 11534606
TI  - Determination of Ba, Cd, Cu, Pb and Zn in saliva by isotope dilution direct
      injection inductively coupled plasma mass spectrometry.
AB  - Trace elements in small sample volumes of saliva were determined by coupling a
      high efficiency direct injection nebulizer to inductively coupled plasma mass
      spectrometry and employing quantification by isotope dilution. Aliquots of 0.4 ml
      of human saliva were mixed with 0.1 ml of concentrated nitric acid and diluted to
      2 ml with water. Sample solutions were spiked with an isotopic solution enriched
      in 135Ba, 112Cd, 65Cu, 206Pb and 66Zn. The amount of each isotope added to the
      samples and the measurement procedure were adjusted to attain precise analytical
      results calculated from the isotope ratios 135Ba/138Ba, 112Cd/114Cd, 65Cu/63Cu,
      206Pb/208Pb and 66Zn/68Zn. Data acquisition for Ba, Cu and Zn isotopes was
      performed for a single sample injection of 50 microl and in another sample
      injection the Cd and Pb isotopes were measured. Concentrations ranging from 5.0
      to 16 microg l(-1) for Ba, from 0.50 to 1.1 microg l(-1) for Cd, from 6.0 to 50
      microg l(-1) for Cu, from 0.8 to 18.8 microg l(-1) for Pb and from 46.0 to 230
      microg l(-1) for Zn were found in saliva samples. Detection limits of 0.11, 0.03,
      0.40, 0.05 and 0.59 microg l(-1) were determined for Ba, Cd, Cu, Pb and Zn,
      respectively. The concentrations found by isotope dilution were in agreement with
      those of the completely digested samples quantified by external calibration. The
      direct analysis of 30 samples per hour was attained with the proposed procedure,
      avoiding time-consuming digestion steps, contamination risks and matrix effects.

PMID- 11534607
TI  - Interaction of morin-cetyltrimethylammonium bromide with nucleic acids and
      determination of nucleic acids at nanograms per milliliter levels based on the
      enhancement of preresonance light scattering.
AB  - A new preresonance light scattering (PRLS) assay of nucleic acids is presented.
      At pH 7.30, the weak PRLS of morin-cetyltrimethylammonium bromide (CTMAB) can be
      greatly enhanced by the addition of nucleic acids, owing to the interaction
      between the nucleic acid and morin-CTMAB. After the addition of morin and CTMAB
      to DNA, the zeta potential of DNA decreases and changes from negative to
      positive, which is due to the formation of an associate, the aggregation of morin
      on nucleic acids and the electric neutralization between DNA and the cationic
      surfactant CTMAB. Mechanism studies showed that the enhanced PRLS comes from the
      aggregation of morin in the presence of nucleic acids and CTMAB. The enhanced
      intensity of PRLS is in proportion to the concentration of nucleic acids in the
      range 7.5 x 10(-9)-1.0 x 10(-5) g ml(-1) for calf thymus DNA, 7.5 x 10(-9)-1.0 x
      10(-6) g ml(-1) for salmon sperm DNA and 1.0 x 10(-8)-1.0 x 10(-6) g ml(-1) for
      yeast RNA. The detection limits are 3.4, 6.2 and 4.1 ng ml(-1) for calf thymus
      DNA, salmon sperm DNA and yeast RNA, respectively. Synthetic samples were
      analyzed satisfactorily.

PMID- 11534608
TI  - Production of monoclonal antibodies against a major purgative component,
      sennoside B, their characterization and use in ELISA.
AB  - For immunization, sennoside B was conjugated with bovine serum albumin. The
      hapten density in the antigen conjugate was determined to be 3 mol mol(-1)
      protein by matrix-assisted laser desorption-ionization TOF mass spectrometry. A
      hybridoma secreting monoclonal antibody against sennoside B was produced by
      fusing splenocytes from mouse immunized with the sennoside B conjugate and mouse
      myeloma cells. Weak cross-reactivities occurred with sennoside A which is a
      stereochemical isomer, and a monomer of sennoside B, rhein, but no cross
      reactivity was observed with other related anthraquinones and phenolics. The
      range of the assay extended from 0.5 ng ml(-1) to 15 ng ml(-1) of sennoside B,
      and good correlation between ELISA and HPLC methods was obtained when crude
      extracts of rhubarb were analyzed.

PMID- 11534609
TI  - Microstructural and surface characterization of solid state sensor based on
      LaFeO3-sigma oxide for detection of NO2.
AB  - NO2 adsorption on non-stoichiometric perovskite-type LaFeO3-sigma thick films
      increases the density of charge carriers (holes), thus facilitating the detection
      of NO2 by conduction measurements. In this work, the microstructures and induced
      defects that control the sensing behaviour of LaFeO3-sigma were investigated in
      depth. LaFeO3-sigma powders were prepared both by thermal decomposition of a
      La[Fe(CN)6].nH2O complex at 700 degrees C and by using a sol-gel method at 500
      degrees C. Scanning electron microscopy (SEM) revealed crystallites varying in
      size from 100 to 300 nm depending on the decomposition temperature. Surface
      analysis by X-ray photoelectron spectroscopy (XPS) confirmed that sintering in
      nitrogen is much more effective for reducing the amount of surface oxygen than is
      sintering in air. At low operating temperature, there is a drift of the output
      response associated with the ongoing process of bulk equilibration, but it is
      much less at 350 degrees C. It is obvious that a variation of [Oad]/[Olattice]
      with sintering conditions represents the relative gas adsorption capability.

PMID- 11534610
TI  - Detection of chlorinated methanes by tin oxide gas sensors.
AB  - Tin oxide thin films prepared by thermal oxidation of Sn films were used for the
      detection of chlorinated methanes (CH2Cl2, CHCl3 and CCl4). This resulted in
      better chemical selectivity, sensitivity, response speed and detection limit than
      seen with previous detectors. The temperature dependence of the sensing of 1%
      CCl4 gas was studied and the best sensing behavior was observed at 300 degrees C.
      The films showed different chemical selectivity in both speed and direction of
      sensing response to each gas and were stable for more than 3 weeks under
      operating conditions. The films showed rapid gas sensing (<40 s to reach 90% of
      full response) and low detection limits (< 4 ppm CCl4). The role of oxygen in the
      detection of chlorinated methanes and in resistance changes without chlorinated
      methanes was also studied. The changes at the surface of the film after gas
      sensing were examined using scanning electron microscopy with energy-dispersive X
      ray spectrometry.

PMID- 11534611
TI  - Synchronous fluorescence and absorbance dynamic liquid drop sensor for cr(VI)
      determination at the femtomole level.
AB  - A novel synchronous fluorimetric and absorptiometric technique based on dynamic
      liquid drops coupled with flow injection is described for the determination of
      chromium(VI) in aqueous solutions. Drops formed continuously at the end of a
      quartz capillary tube serve as reactor and optical cell. The reaction between
      chromium(VI) and 3,3',5,5'-tetramethylbenzidine dichloride (TMB-d) results in a
      significant decrease in fluorescence and transmitted light intensity,
      proportional to the logarithm of the concentration of chromium(VI). The
      transmitted light and fluorescence emission are detected in counter and
      perpendicular positions of the excitation light by a photomultipler tube and
      photodiode, respectively. In HCl-NaOAc buffer solution (pH 3.29), the sensor has
      a wide linear calibration range of 2 x 10(-8)-1 x 10(-4) mol l(-1) chromium(VI)
      with an absolute mass detection limit of 12.88 fmol.

PMID- 11534612
TI  - Reagentless chemiluminescence flow sensor for the determination of riboflavin in
      pharmaceutical preparations and human urine.
AB  - A novel continuous-flow sensor based on chemiluminescence (CL) detection was
      developed for the determination of riboflavin at pg ml(-1) levels by the
      immobilization of the reagents. It was found that the CL intensity from the
      oxidation between luminol and periodate could be enhanced in the presence of
      riboflavin. The increase of CL emission was correlated with the riboflavin
      concentration in the range from 0.04 to 200 ng ml(-1), and the detection limit
      was 0.02 ng ml(-1) (3s). Considering the effective reaction ions, luminol and IO4
      was immobilized on anion-exchange resin. The system could produce an evident CL
      signal by water as eluant and it was also shown that the flow sensor could
      greatly improve the selectivity and sensitivity for determination of riboflavin
      with a high signal-to-noise ratio. A complete analysis, including sampling and
      washing, could be performed in 0.5 min with a relative standard deviation of less
      than 3.0%. The flow sensor was applied successfully to the determination of
      riboflavin in pharmaceutical preparations and human urine samples.

PMID- 11534613
TI  - Effect of pre-treatment on the surface and electrochemical properties of screen
      printed carbon paste electrodes.
AB  - The effect of various electrochemical pre-treatment methods on the surface and
      electrochemical properties of screen-printed carbon paste electrodes (SPCE)
      prepared with three different commercial products was examined. It was observed
      that a positively charged redox couple, e.g., hexaammineruthenium(III), exhibited
      quasi-reversible behavior at the untreated SPCE. However, the cyclic
      voltammograms (CVs) of the SPCE prepared with general-purpose carbon inks did not
      exhibit clear redox peaks to other representative redox couples [e.g.,
      hexacyanoferrate(III), hexachloroiridate(IV), dopamine, and hydroquinone] without
      activation. Electrochemical pre-treatment methods were sought in four different
      aqueous solutions, i.e., sulfuric acid, potassium chloride, sodium
      hydrogencarbonate, and sodium carbonate, applying various activation potentials.
      It was found that the pre-treatment procedure in saturated Na2CO3 solution at 1.2
      V provides a mild and effective condition for activating the SPCE. By measuring
      the water contact angles at the SPCE surfaces and recording their SEM images, it
      was confirmed that the electrochemical pre-treatment effectively removes the
      organic binders from the surface carbon particles. A prolonged period of
      activation (> 5 min) or the use of high potentials (> 1.2 V) increased the
      capacitance of the electrode over 20 microF cm(-2). The pre-treated SPCE behaved
      like a random array microelectrode, exhibiting a sigmoidal-shaped CV at a slow
      scan rate. The short pre-anodization method in Na2CO3 solution was generally
      applicable to most SPCE prepared with general-purpose carbon inks.

PMID- 11534614
TI  - Speciation of aluminium(III) in natural waters using differential pulse
      voltammetry with a pyrocatechol violet-modified electrode.
AB  - A differential pulse voltammetric (DPV) procedure is proposed for the speciation
      of aluminium in natural waters using Pyrocatechol Violet chemically modified
      electrodes (PCV-CMEs). This novel speciation idea is based on the selective
      determination of different AlIII forms under two pH conditions. The labile
      monomeric Al fraction (mainly inorganic Al) is analysed at pH 4.8 (0.20 mol dm(
      3) NaOAc-HOAc) and the total monomeric Al fraction is analysed at pH 8.5 (0.20
      mol dm(-3) NH3.H2O-NH4Cl). The difference is thought to be caused by the weak
      competition ability of PCV to sequester AlIII from AlIII-natural organic matter
      complexes. This sensitive and simple speciation method has been applied
      successfully to aluminium speciation in natural waters sampled from different
      regions of China. Five fractions are measured directly or indirectly: (i) labile
      monomeric Al; (ii) total monomeric Al; (iii) acid reactive Al; (iv) non-labile
      monomeric Al; and (v) acid soluble Al. The results are in satisfactory agreement
      with those obtained by Driscoll's 8-hydroxyquinoline extraction-ion exchange
      method.

PMID- 11534616
TI  - A new test for 'sufficient homogeneity'.
AB  - Certified reference materials and materials distributed in proficiency testing
      need to be 'sufficiently homogeneous', that is, the variance in the mean
      composition of the distributed portions of the material must be negligibly small
      in relation to the variance of the analytical result produced when the material
      is in normal use. The requirement for sufficient homogeneity suggests the use of
      a formal test. Such tests as have been formulated rely on the duplicated analysis
      of the material from a number of portions, followed by analysis of variance.
      However, the outcome is not straightforward. If the analytical method used is
      very precise, then an undue proportion of the materials will be found to be
      significantly heterogeneous. If it is too imprecise, the test may be unable to
      detect heterogeneity. Moreover, the Harmonised Protocol Procedure (M. Thompson
      and R. Wood, Pure Appl. Chem., 1993, 65, 2123) seems to be unduly prone to the
      rejection of material that is in fact satisfactory. We present a simple new
      statistical approach that overcomes some of these problems.

PMID- 11534615
TI  - Electrocatalytic cyclization of dithiothreitol on a chemically modified electrode
      by analogy with protein action.
AB  - Electrocatalytic oxidative cyclization of dithiothreitol (DTT(SH)2) to a
      disulfide product was demonstrated on a Nafion/lead-ruthenium oxide pyrochlore
      chemically modified electrode (NPyCME). The process at the NPyCME with DTT(SH)2
      is similar to the behaviour of protein in a disulfide linkage, which can be
      demonstrated by product analysis using HPLC coupled with UV spectroscopy. A
      possible electrocatalytic mechanism for DTT(SH)2 oxidation to dihydroxydithiane
      [i.e. cyclized DTT(S-S)] on the NPyCME was proposed in terms of Py-Ru(IV)/Py
      Ru(VI) redox active sites. This physical aspect was further utilized for high
      precision analytical assays using flow injection analysis (FIA), with a linearity
      up to 50 microM and a detection limit (S/N = 3) of 28 nM (8.64 pg) in a 20 microL
      sample loop. This is the most sensitive method ever reported for DTT(SH)2
      detection assays. The interference from dissolved oxygen, disulfide and glucose
      is almost negligible. The present method offers an easy route for extension to
      redox-related protein studies.

PMID- 11534617
TI  - Applicability of surface-enhanced resonance Raman scattering for the direct
      discrimination of ballpoint pen inks.
AB  - In situ surface-enhanced resonance Raman spectroscopy (SERRS) with excitation at
      685 nm is suitable for the direct discrimination of blue and black ballpoint pen
      inks on paper. For black inks, shorter excitation wavelengths can also be used.
      For blue inks, SERRS at 514.5 and 457.9 nm does not provide adequate
      discriminative power. At these excitation wavelengths, the SERRS signals of the
      Methyl Violet derivatives present in inks easily dominate the overall spectrum
      because of resonance enhancement and preferential interaction with silver sol
      particles. At 685 nm, this problem is not encountered as the Methyl Violet
      derivatives do not show resonance enhancement, while other components may still
      exhibit resonance. Thirteen blue and thirteen black ink lines were examined. For
      the blue and black inks, on the basis of the 685 nm SERR spectra, eight and six
      groups of spectra, respectively, could be distinguished. This discrimination
      largely agrees with information from thin layer chromatography (TLC) experiments,
      although some differences in group compositions are found. The in situ SERR
      spectra show good repeatability with regard to the Raman frequencies, band shapes
      and relative intensities of the spectral bands. However, absolute intensities
      cannot be used for discrimination purposes.

PMID- 11534618
TI  - Determination of nitrite by inhibition of the chemiluminescence of acriflavine in
      a flow-injection assembly.
AB  - The indirect determination of nitrite was performed with a flow-injection
      assembly on the basis of the inhibition of the analytical output obtained in a
      luminometer by oxidation of acriflavine. The acriflavine solution merged with the
      nitrite and the resulting mixture was injected into a pure water stream. This
      solution merged with the oxidant solution (potassium permanganate in sulfuric
      acid medium) and the resulting chemiluminiscence was affected (inhibited) by the
      presence of nitrite after reaction with the aminoacridine. The method was
      applicable over the range 10-800 microg l(-1) of nitrite with a correlation
      coefficient of 0.9960. The relative standard deviation was 1.4% and the
      throughput was 76 samples h(-1). The influence of foreign substances was also
      tested. A solid-phase reactor, filled with Amberlite IRA-900, was inserted in the
      assembly for the on-line preconcentration of nitrite; the analytical output
      resulted in an increase of up to 11.5-fold. The method was applied to the
      determination of nitrites in residual waters, industrial formulations and soil
      samples.

PMID- 11534619
TI  - Stopped-flow Fourier-transform infra-red spectrometric speciation of glycolic and
      lactic acids in cosmetic formulations.
AB  - The dermatological activity of cosmetic formulations containing alpha
      hydroxyacids depends on their different chemical forms, and it is therefore
      useful to determine these species in the finished products. In the present report
      a new procedure for studying the protonation equilibria of glycolic and lactic
      acids by stopped-flow Fourier-transform infra-red (FTIR) spectrometry is
      described. The procedure was validated for use in the speciation of glycolic and
      lactic acids in cosmetic formulations, with preferential attention given to
      glycolic acid, which is the most widely used. Species of these alpha-hydroxyacids
      can be approximately determined at different pHs and the total content of each
      alpha-hydroxyacid can be accurately determined (according to the Student t-test
      at 5% significance level). The recovery of the total content of glycolic acid
      from commercial cosmetic formulations was 101+/-4%. The RSD of the determinations
      of the total content and those of the species was of the order of 2-7%.

PMID- 11534620
TI  - Vapour phase Fourier transform infrared spectrometric determination of thiourea.
AB  - A novel and precise procedure for the determination of thiourea based on vapour
      generation Fourier transform infrared spectrometry is described. A 4 ml volume of
      1.4% m/v iodine solution was injected into a glass vessel containing 5 ml of
      thiourea and 0.2 ml of 1 M sodium hydrogencarbonate solution. The CO2 evolved
      under these conditions was swept by a stream of nitrogen to an infrared gas cell.
      At 200 s after injection of the iodine solution, the vapour phase FTIR spectra
      were continously recorded, as a function of time, between 2500 and 2200 cm(-1),
      which includes the CO2 absorption band at 2350 cm(-1). From the absorbance data
      in the 2399-2284 cm(-1) range, integrated absorbance measurements were obtained
      providing transient recordings which correspond to the absorbance of CO2 in the
      selected wavenumber range. The method provided a limit of detection of 10 ppm of
      thiourea, a throughput of 14 samples h(-1) and an RSD of 1.1% for three
      independent analyses of a 500 ppm thiourea solution. Results obtained for a
      series of real samples compared well with those obtained using potentiometric
      titration as a reference method.

PMID- 11534622
TI  - Study of the absorption spectra of the 4f electron transitions of the
      praseodymium complex with ciprofloxacin and its analytical application.
AB  - Ciprofloxacin (CPFX) is proposed as a reagent for the derivative
      spectrophotometric determination of praseodymium in mixed rare earths. The
      absorption spectra of 4f electron transitions of the praseodymium complex with
      CPFX was studied by normal and derivative spectrophotometry. The stoichiometry of
      the praseodymium-CPFX complex was calculated by the molar ratio and continuous
      variations methods. A ratio of Pr to CPFX of 1:3 was found. The absorption bands
      of the 4f electron transitions of the complex were enhanced markedly. Using the
      third derivative spectrum. Beer's law was obeyed up to 35 microg cm(-3) of
      praseodymium. The relative standard deviation is 0.62% for 14 microg cm(-3) of
      praseodymium. The detection and quantification limits were 0.17 and 0.56 microg
      cm(-3) of praseodymium, respectively. A method for the direct determination of
      praseodymium in mixtures of rare earths with good accuracy and selectivity is
      described.

PMID- 11534621
TI  - Fluorimetric determination of total ascorbic acid by a stopped-flow mixing
      technique.
AB  - A simple, rapid and automatic fluorimetric method for the determination of total
      ascorbic acid is described. The method makes use of the stopped-flow mixing
      technique in order to achieve the rapid oxidation of ascorbic acid by dissolved
      oxygen to dehydroascorbic acid, which then reacts with o-phenylenediamine to form
      a fluorescent quinoxaline. The initial rate and fluorescence signal of this
      system are directly proportional to the ascorbic acid concentration. The
      calibration graph was linear over the range 0.1-30 microg ml(-1) (kinetic method)
      and 0.25-34 microg ml(-1) (equilibrium method). The precision (% RSD) was close
      to 0.5%. The method has been used for the determination of ascorbic acid in
      pharmaceutical formulations, fruit juices, soft drinks and blood serum.

PMID- 11534623
TI  - A sensitive and rapid method for the determination of protein by the resonance
      Rayleigh light-scattering technique with Pyrogallol Red.
AB  - The resonance Rayleigh light-scattering (RRLS) technique was used to develop a
      simple, sensitive and selective method for the determination of proteins. The
      method is based on the interaction between proteins and Pyrogallol Red (PR) in
      the pH range 3.6-4.2, which causes a substantial enhancement of the resonance
      scattering signal of PR in the wavelength range 300-450 nm with the maximum
      scattering peak located at 347 nm. With this method, 0.25-13 microg ml(-1) of
      bovine serum albumin (BSA), 0.25-10 microg ml(-1) of human serum albumin (HSA)
      and 0.25-13 microg ml(-1) of human immunoglobulin G (IgG) can be determined, and
      the detection limits, calculated as three times the standard deviation of nine
      blank measurements, for BSA, HAS and IgG were 51, 48 and 57 microg l(-1),
      respectively. Moreover, the method shows almost no protein-to-protein variability
      and is free from interference from many amino acids and metal ions. The method,
      with high sensitivity, selectivity and reproducibility, was satisfactorily
      applied to the determination of the total protein in human serum and saliva
      samples. Mechanism studies indicated that PR can bind to BSA depending mainly on
      electrostatic forces, and this interaction can encourage the J-aggregation of PR,
      which results in enhanced Rayleigh light-scattering in the PR-protein system.

PMID- 11534624
TI  - Determination of tellurium in indium antimonide semiconductor material by
      electrothermal atomic absorption spectrometry.
AB  - A method for the determination of the dopant concentration of tellurium in
      dissolved indium antimonide semiconductor material by electrothermal atomic
      absorption spectrometry (ETAAS) was developed. Efforts were made to investigate
      the optimal conditions of the furnace heating program and the effect of palladium
      modifier on the variation of tellurium and the background absorbance. According
      to the results obtained, the presence of palladium chemical modifier in the
      analysis of indium antimonide allowed the successful retention of tellurium in
      the graphite tube, and the optimum mass of palladium modifier was found to be
      dependent on the sample matrix concentration. The absorbance profile of tellurium
      and the background level were significantly improved when a pyrolysis temperature
      of 1100 degrees C and an atomization temperature of 2200 degrees C were employed
      in the optimized heating program. With the use of this method, a detection limit
      of 0.8 microg g(-1) tellurium in indium antimonide could be achieved. The
      applicability of the proposed method was evaluated by comparison with two
      independent methods, i.e. slurry sampling-ETAAS and ICP-MS. From the good
      agreement between the results, it was demonstrated that the proposed method is
      suitable for the determination of typical dopant concentrations of tellurium in
      indium antimonide.

PMID- 11534625
TI  - Separation and preconcentration of chromium species by selective absorption on
      Lemna minor and determination by slurry atomisation electrothermal atomic
      absorption spectrometry.
AB  - A novel method for the separation and preconcentration of Cr(III)/Cr(VI) with
      Lemna minor and determination by slurry atomization electrothermal atomic
      absorption spectrometry (ETAAS) was developed. A sample solution was added to a
      polyethylene beaker containing 10 mg of 160 mesh pre-treated Lemna minor,
      adjusted to pH 1.0, stirred for 8 min for selective absorption of Cr(III) and
      then centrifuged. The upper layer of solution was transferred into another
      polyethylene beaker containing 10 mg of 160 mesh pre-treated Lemna minor,
      adjusted to pH 5.0, stirred for 12 min for adsorption of the residual Cr(VI) and
      centrifuged. The two residues in two centrifuge tubes were washed twice with
      water, 2 ml of agar solution added, stirred for 2 min, then two slurries were
      prepared and used for the determination of Cr(III) and Cr(VI) by ETAAS. Detection
      limits (3sigma) of 0.01 microg L(-1) for Cr(III) and 0.03 microg L(-1) for Cr(VI)
      were obtained. The relative standard deviation was 2.8% for Cr(III) and 3.3% for
      Cr(VI) at the 1 microg L(-1) level. The method was applied to the determination
      of Cr(III)/Cr(VI) in water samples. The analytical recoveries of Cr(III) and
      Cr(VI) added to samples were 97-102 and 96-103%, respectively.

PMID- 11534626
TI  - Biological sample analysis with immunoaffinity solid-phase microextraction.
AB  - A theophylline antiserum was covalently immobilized on the surface of a fused
      silica fiber, modified with 3-aminopropyltriethoxysilane (APTES) and
      glutaraldehyde, and used as a selective and sensitive extraction medium for the
      immunoaffinity solid-phase microextraction (SPME) determination of theophylline
      in serum samples. The specificity of the immunoaffinity SPME fiber was first
      investigated using a fixed concentration of [3H]theophylline together with
      various amounts of interference, possessing no cross-reactivity with the
      theophylline antibody. No significant non-specific binding was observed. The
      reproducibility of the fiber preparation and the immunoaffinity SPME analysis was
      also investigated, resulting in a relative standard deviation of 6.1% for five
      analyses of the same fiber. The antigen-antibody binding isotherm was obtained by
      analyzing theophylline standards of various concentrations (0.1-5 ng mL(-1))
      until saturation values were reached. Initial binding of theophylline was linear
      with a r2 = 0.968. The cross-reactivity of the theophylline immunoaffinity SPME
      fiber for the structural analog caffeine was investigated by adding various
      amounts of caffeine in the presence of theophylline at a saturation concentration
      and produced a low cross-reactivity value of 0.1%. Finally. spiked serum samples
      (10 and 50 ng mL(-1)) were successfully analyzed with an excellent correlation
      with the standard binding isotherm, thus confirming the performance of the
      immunoaffinity SPME coating for improved bioanalysis.

PMID- 11534627
TI  - Sequential injection spectrophotometric determination of oxybenzone in lipsticks.
AB  - A sequential injection (SI) procedure for the spectrophotometric determination of
      oxybenzone in lipsticks is reported. The colorimetric reaction between nickel and
      oxybenzone was used. SI parameters such as sample solution volume, reagent
      solution volume, propulsion flow rate and reaction coil length were studied. The
      limit of detection was 3 microg ml(-1). The sensitivity was 0.0108+/-0.0002 ml
      microg(-1). The relative standard deviations of the results were between 6 and
      12%. The real concentrations of samples and the values obtained by HPLC were
      comparable. Microwave sample pre-treatment allowed the extraction of oxybenzone
      with ethanol, thus avoiding the use of toxic organic solvents. Ethanol was also
      used as carrier in the SI system. Seventy-two injections per hour can be
      performed, which means a sample frequency of 24 h(-1) if three replicates are
      measured for each sample.

PMID- 11534628
TI  - Determination of ascorbyl 6-palmitate in food matrices by amperometric flow
      injection analysis.
AB  - In this paper a rapid method based on a FIA (flow injection analysis) system with
      amperometric detection for the evaluation of ascorbyl 6-palmitate in foods is
      described. The selectivity of the proposed method is related to the low anodic
      potential applied to the working glassy carbon electrode (+0.1 V vs. Ag/AgCl)
      that leaves out interferences from ascorbic acid and phenolic compounds. By flow
      injection analysis, under optimised conditions, the calibration curve was linear
      in the range 0-20 mg l(-1) and the detection limit was 0.2 mg l(-1).

PMID- 11534629
TI  - Optical fibre biosensors based on immobilised enzymes.

PMID- 11534630
TI  - Cultural and physiological observations on Trypanosoma rhodesiense and
      Trypanosoma gambiense. 1949.
AB  - 1. A diphasic medium of simple preparation is described for the indefinite
      cultivation of T. rhodesiense and T. gambiense. 2. The chief advantage of the
      medium is that it contains rabbit blood and thus obviates the necessity of using
      human blood. 3. The flagellates develop only to the proventricular stage; hence
      the cultures are noninfective. 4. The proventricular forms of both T. rhodesiense
      and T. gambiense consume sugar with the concomitant formation of acid. They are
      aerobic fermenters. 5. Very little, if any, ammonia is produced by the living
      parasites.

PMID- 11534631
TI  - The classic paper of Tobie, von Brand, and Mehlman (1950) revisited.

PMID- 11534632
TI  - Effect of surgical alteration of the rat gastrointestinal tract on the growth and
      development of Hymenolepis diminuta.
AB  - Eight groups of rats were used to study the involvement of the enteric (ENS) and
      central (CNS) nervous systems in the development of Hymenolepis diminuta using
      surgical intestinal transection, or CNS denervation, or both procedures. The
      transection procedure was used to isolate the ENS of the small intestine from
      either orad and/or caudal portions of the alimentary system, while the CNS
      denervation was used to eliminate direct visceral efferent inputs from the CNS.
      Nine days after the surgical procedures, all rats were infected with 35
      cysticercoids of H. diminuta. On 20 days postinfection, the infection intensity,
      tapeworm dry weight, tapeworm morphology, intestine length, and intestinal wet
      weight were recorded. Only the combination of the duodenal and ileal transections
      with a CNS denervation reduced infection intensity and prevented the increased
      intestinal length normally observed in infected rats. In contrast, none of the
      various intestinal transection procedures alone or CNS denervation alone had any
      effect on the survival, ability to produce oncospheres or morphology of the
      tapeworms. In conclusion, tapeworm survival is decreased when both CNS and ENS
      inputs into the small intestine are altered or absent.

PMID- 11534633
TI  - Alterations in the levels of glycogen and glycogen synthase transcripts during
      desiccation in the insect-killing nematode Steinernema feltiae IS-6.
AB  - The ability to withstand desiccation by entering anhydrobiosis is important for
      the survival of many nematode species. We are interested in the metabolic changes
      that occur during dehydration in the semiarid strain IS-6 of the insect parasitic
      nematode Steinernema feltiae. These changes may enable IS6 to be more tolerant to
      desiccation than temperate strains. We identified genes of IS-6 that exhibit
      changes in transcript levels during dehydration. These included glycogen synthase
      (Sf-gsy-1), which is the rate-limiting enzyme in the synthesis of glycogen, which
      is likely to play a role in desiccation survival. We established the changes in
      the steady state level of Sf-gsy-1 transcripts upon dehydration and determined
      the biochemical changes in the level of its product, glycogen, during the
      dehydration and rehydration of nematodes. Our results suggest a shift from
      glycogen to trehalose synthesis during dehydration, which is regulated at least
      in part by suppression of glycogen synthase transcription.

PMID- 11534634
TI  - In vitro reactivation of Ancylostoma caninum tissue-arrested third-stage larvae
      by transforming growth factor-beta.
AB  - Developmental arrest in Ancylostoma caninum is associated with preparasitic, free
      living third-stage (L3) larvae, as well as anthelmintic-resilient hypobiotic L3
      larvae within the tissues of an infected dog. With the tissue-arrested larvae,
      pregnancy and, more specifically, the hormonal effects of estrogen and prolactin
      mediate reactivation resulting in transmammary transmission of infection to
      nursing puppies. Estrogen and prolactin have been shown to be critically involved
      in upregulation of transforming growth factor (TGF)-beta2 during pregnancy, and
      studies on the soil nematode Caenorhabditis elegans further implicate TGF-beta
      and insulin-like signaling pathways with larval arrest and reactivation. In this
      report, an in vitro assay was used to show that neither estrogen, prolactin, nor
      insulin had a direct effect on the feeding/reactivation response of tissue
      arrested larvae; however, TGF-beta isoforms 1 and 2 both had significant
      stimulatory effects that were comparable to the effects of dog serum. The
      stimulatory effects of serum could be blocked by preincubation with anti-TGF-beta
      antibodies. Taken together, the results support the hypothesis that during
      pregnancy, host-derived TGF-beta can signal a parasite-encoded receptor to
      trigger the reactivation of tissue-arrested larvae. TGF-beta had no effect on
      preparasitic larvae, suggesting that different signals may be involved in
      reactivation of the 2 different arrested forms of A. caninum L3 larvae.

PMID- 11534636
TI  - Population dynamics of Ornithodiplostomum ptychocheilus metacercariae in fathead
      minnows (Pimephales promelas) from four northern-Alberta lakes.
AB  - Annual, seasonal, and interlake variation in prevalence and intensity of
      Ornithodiplostomum ptychocheilus (Faust) metacercariae was assessed in
      populations of fathead minnows (Pimephales promelas) collected from 4 lakes in
      north-central Alberta. Mean metacercariae intensity in young-of-the-year minnows
      varied extensively (5-123 metacercariae/host) among year, month, and lakes. In 2
      of the lakes, prevalence always reached 100%, and mean intensity always peaked in
      September or October. The high spatial and annual variation in metacercarial
      recruitment was partly attributable to variation in host size. but variation in
      water depth, temperature, snail densities, and bird visitation likely also played
      a role. A laboratory experiment demonstrated that host and metacercariae survival
      was intensity-independent during a period of simulated winter. Thus,
      metacercariae recruited in the fall survive until the following spring.

PMID- 11534635
TI  - Epidemiology of Necator americanus hookworm infections in Xiulongkan Village,
      Hainan Province, China: high prevalence and intensity among middle-aged and
      elderly residents.
AB  - Hookworm is highly endemic to Hainan Province, an island located in the South
      China Sea. To investigate the prevalence and intensity of infection in the area,
      the village of Xiulongkan was surveyed between April and July 1998. A cross
      sectional study was conducted in which fecal samples of 80% of the village
      residents (631 individuals) were tested for the presence of helminth eggs.
      Hookworm was the predominant intestinal helminth in Xiulongkan, where it was
      determined that 60% of those tested were infected. Necator americanus was the
      predominant species of hookworm in this population. The prevalence of hookworm
      increased with age, and then leveled to a plateau for ages 41 yr and up. This
      observation was in contrast to infections with Ascaris lumbricoides, where the
      highest prevalences occurred among school-aged children. Women had a
      significantly higher prevalence of hookworm than men and this difference emerged
      in early adulthood. The intensity of hookworm infection also significantly
      increased with age, with the highest intensity infections occurring among middle
      aged and elderly residents. Females were more likely to have moderate or heavy
      infections, whereas males were more likely to have light infections. The rates of
      hookworm transmission are particularly high among the middle-aged and elderly
      residents of Xiulongkan.

PMID- 11534637
TI  - Haliotrema abaddon n. sp. (Monogenoidea: Dactylogyridae) from the gills of wild
      and maricultured West Australian dhufish Glaucosoma hebraicum (teleostei:
      Glaucosomatidae), in Australia.
AB  - Haliotrema abaddon n. sp. (Dactylogyridae) is described from the gills of West
      Australian dhufish Glaucosoma hebraicum (Teleostei: Glaucosomatidae), from the
      Indian Ocean near Fremantle, Western Australia. The parasite is recorded from
      cultured dhufish and from a major portion of the known geographic distribution of
      its host. In cultured dhufish, H. abaddon causes branchitis and hyperplasia and
      metaplasia of the lamellar epithelial cells and may be a limiting factor in the
      development of an economically feasible mariculture industry. Comparable
      prevalences and densities of the parasite on wild and cultured dhufish were
      observed. In heavily infested captive fish, clusters of eggs (egg strands) appear
      to restrict blood flow to localized regions of the gills as a result of
      entanglement of egg filaments with secondary gill lamellae. Hatching of
      oncomiracidia occurs in 7-10 days at 20-25 C.

PMID- 11534638
TI  - Birds and their ticks in northwestern California: minimal contribution to
      Borrelia burgdorferi enzootiology.
AB  - Birds and their attendant ticks were surveyed for infection with the Lyme disease
      spirochete Borrelia burgdorferi, in chaparral and woodland-grass habitats in
      northwestern California from March to July, 1998 to 1999. In total, 234 birds
      were captured and recaptured (15%); nearly 2.5 times more birds were captured in
      chaparral than in woodland-grass. Overall, 34 species representing 15 families
      were collected during this study; of these, 24 species were caught in chaparral,
      19 in woodland-grass, and 9 in both vegetational types. The most frequently
      captured birds were sage sparrows (Amphispiza belli) in chaparral, and American
      robins (Turdus migratorius) and oak titmice (Baelophus inornatus) in woodland
      grass. Birds hosted 35 Ixodes pacificus (15 larvae, 20 nymphs) and 9
      Haemaphysalis leporispalustris (3 larvae, 5 nymphs, 1 adult) ticks, of which 32
      were removed from chaparral birds and 12 from woodland birds. The prevalence of
      tick infestation was 13% (21/167) in chaparral and 5% (3/67) in woodland-grass,
      but the relative and mean tick intensities of 0.19 and 1.5 for chaparral birds,
      and 0.18 and 4.0 for woodland birds, respectively, did not differ significantly
      by habitat. Spirochetes were not detected in either bird-blood or tick-tissue
      samples when tested by culture, immunofluorescence, or Giemsa-staining. In
      contrast, over 90% (86/94) of western fence lizards (Sceloporus occidentalis)
      collected in June or July were infested with an average of 6.9 and 8.9 immature
      I. pacificus in chaparral and woodland-grass, respectively. We conclude that
      birds contribute little to the enzootiology of B. burgdorferi in chaparral and
      woodland-grass habitats in northwestern California because of their limited
      parasitism by tick vectors and lack of detectable spirochetemias.

PMID- 11534639
TI  - Genetic diversity of a population of Schistosoma haematobium derived from
      schoolchildren in east central Zimbabwe.
AB  - To characterize the extent of genetic diversity of Schistosoma haematobium within
      and among its definitive host (intra- and interhost parasite diversity), 133
      individual isolates from 25 infected schoolchildren were compared using randomly
      amplified polymorphic DNA markers. With 4 primers, 53 unambiguous loci were
      identified, and of these, 22 were polymorphic. Mean heterozygosity in the
      population was 0.116 +/- 0.043. Analysis of molecular variance showed the
      majority of variance occurred within, rather than between, hosts. Frequencies of
      certain alleles segregated the parasite population into 13 distinct clusters of
      associated genotypes, with 4 of these first appearing 10 mo after the initial
      survey. Considering the level of diversity within this limited geographical area
      and the possibility of rapid turnover of genotypes, parasite variance may impact
      acquired immunity and clinical outcome of the infection.

PMID- 11534640
TI  - Immunological and biochemical analysis of glycosylated surface antigens and
      lipophosphoglycan of Tritrichomonas foetus.
AB  - Immunoaffinity-purified TF1.17 adhesin antigen was compared biochemically and
      antigenically to Tritrichomonas foetus (TF) lipophosphoglycan (LPG) and a soluble
      glycosylated antigen (SGA) released from T. foetus and implicated in pathogenesis
      and immunity. The monoclonal antibodies (Mabs TF1.15 and TF1.17) specific for a
      glycosylated TF1.17 antigen were previously shown to prevent adhesion of the T.
      foetus parasites to bovine vaginal epithelial cells and to mediate killing by
      bovine complement. SGA was isolated from T. foetus-conditioned buffer and
      purified by octyl-Sepharose hydrophobic column chromatography. Sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis analysis of SGA showed a major SGA1
      component (approximately 190 kDa) and a minor SGA2 component (50-70 kDa), which
      migrated close to TF-LPG and TF1.17. The carbohydrate and lipid compositional
      analyses of affinity-purified TF1.17 and SGA2 by high-performance liquid
      chromatography (HPLC) and gas-liquid chromatography revealed the presence of
      monosaccharides and fatty acids as found in TF-LPG. All antigens contained
      terminal fucose as determined by alpha-fucosidase digestion followed by HPLC.
      ELISA and western blots were used to further characterize these glycosylated
      antigens and to analyze their relationships. The Mabs TF1.15 and TF1.17 reacted
      very strongly to TF-LPG and SGA2. as well as TF1.17 antigen, indicating that
      these molecules share common epitopes. These Mabs did not react with the SGA1
      component either in ELISA and western blot analyses. Also, the monosaccharide
      composition of SGA1 was very different from the other three antigen, suggesting
      SGA1 was different from LPG, SGA2 and TF1.17. Although LPG reacted with Mabs to
      native TF1.17 antigen, LPG did not induce an immune response in cattle with the
      same route and adjuvant used to produce strong antibody responses to the native
      antigen. The latter response suggests that the tightly bound peptide present in
      the immunoaffinity-purified antigen is necessary for induction of a response to
      (an) epitope(s) in TF-LPG and TF1.17. Furthermore, vaginal fluid from T. foetus
      infected heifers and serum from a cow with a T. foetus-associated pyometra
      recognized both TF1.17 and TF-LPG in western blots. These results suggest that T.
      foetus LPG and SGA2 are related to TF1.17 antigen, which was previously shown to
      play an important role in the pathogenesis and host response in bovine
      trichomoniasis.

PMID- 11534641
TI  - Involvement of nitric oxide in killing of Schistosoma mansoni sporocysts by
      hemocytes from resistant Biomphalaria glabrata.
AB  - In strains of the snail Biomphalaria glabrata (Gastropoda) that are resistant to
      the parasite Schistosoma mansoni (Trematoda), hemocytes in the hemolymph are
      responsible for elimination of S. mansoni sporocysts. The defensive role of
      reactive nitrogen species was investigated in in vitro interactions between
      hemocytes derived from the resistant 13-16-R1 strain of B. glabrata and the
      parasite. The nitric oxide synthase (NOS) inhibitor N(omega)-nitro-L-arginine
      methylester (L-NAME) and the nitric oxide (NO) scavenger 2-(4-carboxyphenyl)
      4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide reduced cell-mediated killing of S.
      mansoni sporocysts. To determine if peroxynitrite (ONOO-) is involved in killing,
      assays were run in the presence of the ONOO- scavengers uric acid and
      deferoxamine. These did not influence the rate of parasite killing, indicating
      that NO is directly responsible for mediating cytotoxicity, but ONOO- is not. The
      combination of the NOS inhibitor L-NAME and catalase, an enzyme that detoxifies
      hydrogen peroxide (H2O2), reduced average sporocyst mortality to a greater extent
      than L-NAME alone. Killing of the sporocysts was, however, not totally inhibited.
      It is suggested that NO and H2O2 are both involved in hemocyte-mediated toxicity
      of 13-16-R1 B. glabrata against S. mansoni sporocysts.

PMID- 11534642
TI  - Larval Schistosoma mansoni excretory-secretory glycoproteins (ESPs) bind to
      hemocytes of Biomphalaria glabrata (Gastropoda) via surface carbohydrate binding
      receptors.
AB  - Flow cytometric analysis of circulating blood cells (hemocytes) of Biomphalaria
      glabrata, molluscan intermediate host of Schistosoma mansoni, revealed the
      presence of 2 overlapping hemocyte subpopulations, designated R1 and R2. R1
      hemocytes are characterized by their smaller size, reduced granularity, and the
      presence of the BGH1 surface epitope, whereas R2 cells are larger, more
      granulated, and generally lack the BGH1 cell marker. Both hemocyte subpopulations
      bound fluorescent dye (Oregon Green)-conjugated excretory-secretory glycoproteins
      (fESPs), although the specific fESP binding signal (geometric mean value), after
      correction for cellular autofluorescence, was greater in the R1 hemocyte
      subpopulation compared to that of the R2 subset. Partial inhibition of fESP
      binding to hemocytes consistently was achieved using various glycoconjugates
      (mucin, asialo-mucin, asialo-fetuin, heparin) and polysaccharides (fucoidan,
      dextran sulfate 8000), suggesting the involvement of hemocyte carbohydrate
      binding receptors (CBRs) in reactions with ESP-associated glycans. Although
      sulfation of carbohydrate ligands contributed significantly to ESP blocking
      activity of some inhibitory polysaccharides and heparin, other sulfated
      proteoglycans (chondroitins A and B, heparan sulfate) were noninhibitory,
      indicating that charge alone was not solely responsible for the observed
      inhibition of hemocyte binding by fESPs. A similar blocking effect by
      desialylated glycoproteins (asialo-mucin, asialo-fetuin) further supports the
      contention that ESP-hemocyte interactions are mediated primarily through CBRs.
      The glycoconjugate inhibitors of ESP binding were only partially effective over a
      range of concentrations and their glycan moieties (oligosaccharides or long-chain
      polymers) comprised a diversity of major sugar groups, suggesting that hemocyte
      CBRs and S. mansoni larval ESPs likely represent a multiple receptor-ligand
      system. Previously reported findings of differential effects of ESPs on a variety
      of in vitro hemocyte functions are consistent with such a hypothesis.

PMID- 11534643
TI  - Acanthoparyphium tyosenense: the discovery of human infection and identification
      of its source.
AB  - Acanthoparyphium tyosenense Yamaguti, 1939 (Digenea: Echinostomatidae), was
      originally reported as an avian intestinal parasite; here, its presence is
      reported in 10 humans in the Republic of Korea. The patients were 9 adults aged
      35-66 yr (males and females) and a young girl aged 7 yr residing in 2 coastal
      villages in Puan-gun, Chollabuk-do. The worms were recovered after treatment with
      praziquantel and purgation with magnesium salts. A total of 158 specimens (1-107
      specimens/individual) was collected, together with varying numbers of other
      intestinal flukes. The patients had eaten various kinds of brackish water
      mollusks caught in an estuary near their villages. Five bivalves and a gastropod
      species suspected as sources of human infection were collected and examined. Two
      bivalves (Mactra veneriformis and Solen grandis) and the gastropod (Neverita
      bicolor) were found to be infected with the metacercariae of A. tyosenense; adult
      flukes were confirmed after the experimental infection of chicks. The results
      show that A. tyosenense infects humans and that brackish water mollusks are the
      source of human infection.

PMID- 11534644
TI  - Isolation of a novel collagen gene (Mj-col-5) in Meloidogyne javanica and
      analysis of its expression pattern.
AB  - Mj-col-5, isolated from the plant parasitic nematode Meloidogyne javanica, has a
      longer carboxy-terminus than other members of the Caenorhabditis elegans COL-6
      subfamily of cuticle collagen, including an extra tyrosine residue, and may form
      altered nonreducible cross-linkages. By semiquantitative determination at
      different life stages, Mj-col-5 transcript was shown to be more abundant in eggs
      than in juveniles/young females and adult females. To characterize further this
      gene's contribution to the changing cuticle of the nematode, we expressed a
      fusion protein containing a nonconserved 58-amino-acid sequence from the putative
      Mj-col-5 gene product and raised rabbit antiserum against the fusion protein. The
      antiserum detected a strongly reacting band (36 kDa, designated MJE36) on western
      blots of M. javanica eggs extracted with beta-mercaptoethanol. MJE36 was
      sensitive to collagenase and was not detected on western blots of extracts from
      M. javanica second-stage juveniles or adult females. A band of the same molecular
      size was detected in Meloidogyne incognita egg extracts but not in those of
      Heterodera avenae. Immunoblot indicated that MJE36 is not present in egg shells
      of M. javanica.

PMID- 11534645
TI  - Factors affecting the virulence of entomopathogenic nematodes to engorged female
      Boophilus annulatus ticks.
AB  - The laboratory trials rank the virulence of entomopathogenic nematode strains (3
      heterorhabditids and 6 steinernematids) to engorged female Boophilus annulatus
      ticks according to 3 parameters of the infection process: the effect of exposure
      time on tick mortality, the quantity of nematodes that penetrate ticks, and the
      rate of tick mortality after the injection of 1, 2, or 3 nematodes. Exposure of
      the ticks to heterorhabditid strains for 6 hr resulted in >80% mortality, but
      only 20 or 65% mortality after exposure to most steinernematids. The quantity of
      nematodes recovered per tick exposed to nematodes for 6 days averaged from 16 to
      141. For steinernematids, a negative correlation was obtained between tick
      mortality and the average quantity of nematodes recovered. Injecting 1 infective
      juvenile from 1 of 2 heterorhabditid strains into each tick resulted in close to
      100% mortality. Increasing the quantity of nematodes injected into each tick had
      little or no additive effect on tick mortality.

PMID- 11534646
TI  - Postnatal challenge infections of congenitally Schistosoma japonicum-infected
      piglets.
AB  - The aim of the present study was to assess the effect of a congenital Schistosoma
      japonicum infection on the establishment, fecundity, and pathogenicity of a
      postnatal challenge infection. Five prenatally S. japonicum-infected piglets
      received a challenge infection (prenatal + challenge group), 5 prenatally
      infected piglets were followed without challenge (prenatal group), and 10
      piglets, born by unexposed sows, served as challenge controls (challenge control
      group). Challenge infections were given 8 wk after the piglets were born (14 wk
      after the primary infection of the sows), and the study lasted another 11 wk.
      Variables included worm burden, tissue egg count, and liver pathology. Worm
      establishment and tissue egg count were comparable in the prenatal + challenge
      group and in the challenge control group, both exceeding at a statistically
      significant level those in the prenatal group. No difference in worm fecundity
      (eggs/female worms/g tissue) was seen between the 3 groups. Liver pathology
      (i.e., portal and septal fibrosis) was more severe in the challenge control group
      compared to the other groups. A congenital S. japonicum infection in piglets thus
      affected neither establishment nor fecundity of a postnatal challenge infection.
      In spite of this, the challenge infection gave rise to much less liver pathology
      than the similarly sized challenge control infection.

PMID- 11534647
TI  - Isolation and characterization of two parasitic protozoa from a Pacific harbor
      seal (Phoca vitulina richardsi) with meningoencephalomyelitis.
AB  - Two species of protozoans were isolated from a harbor seal with fatal
      meninogoencephalitis. Serologic reactivity was detected to both Sarcocystis
      neurona and Toxoplasma gondii. Parasites associated with brain inflammation and
      necrosis reacted only with immunohistochemical stains utilizing polyclonal
      antisera raised against Sarcocystis neurona. However, 2 distinct parasites were
      observed in cell cultures derived from the seal's brain tissue. These parasites
      were separated by mouse passage and limiting dilution. Purified zoites from 1
      isolate (HS1) reacted strongly with polyclonal antiserum to S. neurona and with
      the harbor seal's own serum (1:2,560 for each) on indirect immunofluorescent
      antibody tests (IFAT), but weakly to antisera to T. gondii and Neospora caninum
      (1:40). Zoites from the second isolate (HS2) reacted positively with T. gondii
      polyclonal antiserum (1:81,920) and with the harbor seal's own serum (1:640), but
      weakly to S. neurona and N. caninum antisera (1:80 or less). Amplification and
      sequence analysis of protozoal DNA encoding portions of the 18s ribosomal RNA
      (18s rDNA) and the adjacent first internal transcribed spacer (ITSI) were
      performed for both isolates, and resulting sequences were compared to those from
      similar protozoans. Based on molecular characterization, parasite morphology,
      serologic reactivity, histology, and immunohistochemistry, HS1 was
      indistinguishable from S. neurona, and HS2 was indistinguishable from T. gondii.

PMID- 11534648
TI  - Acute Sarcocystis falcatula-like infection in a carmine bee-eater (Merops
      nubicus) and immunohistochemical cross reactivity between Sarcocystis falcatula
      and Sarcocystis neurona.
AB  - An unidentified Sarcocystis falcatula-like infection was diagnosed in a captive
      bee-eater (Merops nubicus) in a zoo in Florida. The bird died suddenly, probably
      due to protozoa-associated pneumonia. Protozoal schizonts were found in lungs and
      heart, and immature sarcocysts were seen in skeletal muscles. Ultrastructurally,
      schizonts were located in capillary endothelium and merozoites lacked rhoptries,
      consistent with the structure of Sarcocystis species. Sarcocysts were immature,
      microscopic, and contained only metrocytes. The sarcocyst wall had finger-like
      villar protrusions that were up to 0.7 microm long and up to 0.2 microm wide. The
      villar protrusions lacked microtubules, characteristically seen in sarcocysts of
      S. falcatula. Antigenically, parasites in lungs and muscles of the bee-eater
      reacted with a varying intensity with polyclonal rabbit antisera to S. falcatula
      and Sarcocystis neurona. Results indicated that sarcocysts in the bee-eater were
      morphologically different from the reported structure for sarcocysts of other S.
      falcatula infections.

PMID- 11534649
TI  - Erudituncus n. gen. (Tetraphyllidea: Onchobothriidae) with a redescription of E.
      musteli (Yamaguti, 1952) n. comb. and comments on its hook homologies.
AB  - Examination of type and new material of Platybothrium musteli Yamaguti, 1952,
      resulted in the erection of a new genus, Erudituncus, the new combination
      Erudituncus musteli (Yamaguti, 1952), and the redescription of the newly combined
      species. This species exhibits novel hook morphology. Each bothridium bears 2
      pairs of hooks, the axial pair comprising 1 medial and 1 lateral bipronged hook
      and the abaxial pair comprising a lateral unipronged hook and a medial, simple
      hook element. Based on the position of the hook talons, we suggest that the inner
      prong of the axial hooks of Erudituncus is homologous to the single prong of the
      axial hooks of Calliobothrium and the axial prongs of Dicranobothrium,
      Platybothrium, Phoreiobothrium, and Onchobothrium; the outer prong of the axial
      hooks of Erudituncus is homologous to the abaxial prongs of Dicranobothrium,
      Platybothrium, Phoreiobothrium, and Onchobothrium; and the abaxial hooks of
      Erudituncus and Calliobothrium are homologous. Erudituncus musteli was lacking
      from 31 individuals of the type host of record, the triakid shark Mustelus manazo
      Bleeker, 1854, examined for this study, but was obtained from 2 individuals of
      the triakid shark Hemitriakis japanica (Muller and Henle, 1839). Therefore, H.
      japanica is proposed as the probable type host of E. musteli.

PMID- 11534650
TI  - Paraspirura bettinae n. sp. from a South African skink with comments on spirurid
      nematodes from saurians and mammals.
AB  - The spirurid nematode, Paraspirura bettinae n. sp., described from Mabuya
      spilogaster (Scincidae) in South Africa (Molopo Reserve), can be distinguished
      from the single known species of the genus, Paraspirura mabuyae Sandground, 1936
      (also reviewed) by the larger size of the eggs, the shape of the tail of the
      female, and the smaller body size in both sexes. The cephalic anatomy of
      Paraspirura spp. does not fit the original description but appears similar to
      that of spirurid parasites of mammals, Spirura spp. and Protospirura spp.
      Previous descriptions did not mention the rim and bulges in members of
      Protospirura. Paraspirura appears close to Protospirura, particularly to
      Protospirura muricola from the Ethiopian region, but it is distinct because of
      the persistence of the larval caudal tubercles in the adult stage, the simple
      right spicule without alae, and the more developed rim and bulges. The species
      parasitic in saurians may have arisen from Protospirura spp. by capture, or the
      spirurids of mammals may have been derived from species of Paraspirura and
      quickly split into a Protospirura line and a more specialized Spirura assemblage.

PMID- 11534651
TI  - Four new genera and five new species of lecanicephalideans (Cestoda:
      Lecanicephalidea) from elasmobranchs in the Gulf of California, Mexico.
AB  - A total of 53 spiral intestines from 3 species of rays collected in the Gulf of
      California, Baja, Mexico, was examined for cestodes of the order
      Lecanicephalidea. Four new genera and 5 new species were discovered as a result
      of this study. These are Aberrapex senticosus n. gen., n. sp., from Myliobatis
      californica, Paraberrapex manifestus n. gen., n. sp., from Squatina californica
      and Healyum harenamica n. gen., n. sp., Healyum pulvis n. sp. and
      Quadcuspibothrium francisi n. gen., n. sp., from Mobula japanica. Aberrapex n.
      gen. and Paraberrapex n. gen. can be distinguished from all other
      lecanicephalidean genera based on the lack of an apical structure (pars apicalis)
      on their scolex. Aberrapex n. gen. can be distinguished from Paraberrapex n. gen.
      based on the presence of an external seminal vesicle, a vagina positioned lateral
      rather than medial in the proglottid, and an ovary that is tetralobed rather than
      bilobed in cross section. Healyum n. gen. and Quadcuspibothrium n. gen. are
      unique among lecanicephalidean genera, including Aberrapex n. gen. and
      Paraberrapex n. gen., in their possession of a trilobed ovary in cross section.
      Quadcuspibothrium n. gen. can be distinguished from Healyum n. gen. based on its
      unique shape of the acetabula, which are diamond-shaped. The 2 species of Healyum
      n. gen. can be distinguished from one another based on the dimensions and the
      shape of the scolex, the diameter of the suckerlike acetabula, as well as the
      shape of the spiniform microtriches on the acetabular rims. Discobothrium
      arrhynchum is transferred to the genus Aberrapex n. gen. and the original
      description of this species is emended to include details of the vas deferens and
      the uterine duct and uterus. The microtrich patterns of the 5 new species and
      Aberrapex arrhynchum n. comb. are described. These are the first records of
      tapeworms of the Lecanicephalidea from the Gulf of California. Squatina
      californica and Mobula japanica represent new host records for lecanicephalidean
      tapeworms. The ordinal diagnosis of the Lecanicephalidea by Euzet (1994) is
      emended to include these 4 new genera.

PMID- 11534652
TI  - Molecular systematics of Goniodidae (Insecta: Phthiraptera).
AB  - The higher level phylogenetic relationships within the avian feather lice
      (Insecta: Phthiraptera: Ischnocera) are extremely problematic. Here we
      investigate the relationships of 1 family (Goniodidae), sometimes recognized as
      distinct within Ischnocera, using parsimony and likelihood analyses of nuclear
      and mitochondrial DNA sequences. These data support monophyly for a restricted
      definition of traditional Goniodidae, but recognition of this family would result
      in paraphyly of the large heterogeneous family Philopteridae. We show that the
      New World Chelopistes is not related to other members of Goniodidae, despite
      similarities in morphology, but rather is the sister taxon to Oxylipeurus. Within
      Goniodidae, genera are divided into those occurring on Galliformes (the Goniodes
      complex) and those occurring on Columbiformes (the Coloceras complex). Within the
      well-sampled Coloceras complex, or Physconelloidinae, several groups are
      identified. However, traditionally recognized genera such as Coloceras and
      Phvsconelloides appear to be paraphyletic. Whereas the phylogeny of Goniodidae
      reflects some aspects of host relationships, biogeography also influences
      coevolutionary history.

PMID- 11534653
TI  - Phylogeny of nuclear small subunit rRNA genes of hemogregarines amplified with
      specific primers.
AB  - Hemogregarines, apicomplexan intracellular blood parasites, are cosmopolitan in
      distribution and infect a broad range of vertebrate and invertebrate hosts.
      Molecular phylogenetic studies have been hampered by lack of hemogregarine
      specific polymerase chain reaction primers that would allow amplification of
      parasite, but not host, DNA. A novel method for separating parasite and host 18S
      rRNA genes has been developed, and new primers that are specific for
      hemogregarine rRNA genes have been designed. These primers were used to obtain
      sequences from 4 isolates of hemogregarines of lizards from California, the
      Caribbean island of Grenada, eastern Australia, and Israel. Combining these
      results with already published sequences, a preliminary phylogeny of
      hemogregarines and several other apicomplexan taxa has been created. The
      hemogregarines form a monophyletic group and appear to be more closely related to
      coccidia than to Plasmodium species. The difficulty of using 18S genes that have
      multiple copies in some apicomplexan parasites was explored for systematic
      studies.

PMID- 11534654
TI  - Phylogeny of Steinernema travassos, 1927 (Cephalobina: Steinernematidae) inferred
      from ribosomal DNA sequences and morphological characters.
AB  - Entomopathogenic nematodes in Steinernema, together with their symbiont bacteria
      Xenorhabdus, are obligate and lethal parasites of insects that can provide
      effective biological control of some important lepidopteran, dipteran, and
      coleopteran pests of commercial crops. Phylogenetic relationships among 21
      Steinernema species were estimated using 28S ribosomal DNA (rDNA) sequences and
      morphological characters. Sequences of the rDNA internal transcribed spacers were
      obtained to provide additional molecular characters to resolve relationships
      among Steinernema carpocapsae, Steinernema scapterisci, Steinernema siamkavai,
      and Steinernema monticolum. Four equally parsimonious trees resulted from
      combined analysis of 28S sequences and 22 morphological characters. Clades
      inferred from analyses of molecular sequences and combined datasets were
      primarily reliably supported as assessed by bootstrap resampling, whereas those
      inferred from morphological data alone were not. Although partially consistent
      with some traditional expectations and previous phylogenetic studies, the
      hypotheses inferred from molecular evidence, and those from combined analysis of
      morphological and molecular data, provide a new and comprehensive framework for
      evaluating character evolution of steinernematids. Interpretation of
      morphological character evolution on 6 trees inferred from sequence data and
      combined evidence suggests that many structural features of these nematodes are
      highly homoplastic, and that some structures previously used to hypothesize
      relationships represent ancestral character states.

PMID- 11534655
TI  - Haemogregarine specificity in two communities of Florida snakes, with
      descriptions of six new species of Hepatozoon (Apicomplexa: Hepatozoidae) and a
      possible species of Haemogregarina (Apicomplexa: Haemogregarinidae).
AB  - Five species of snakes in Florida, from Palm Beach County in the south and
      Alachua County 450 km to the north, occur in similar habitat but have distinctive
      Hepatozoon species characteristic of each host species. In Palm Beach County,
      Diadophis punctatus is host to Hepatozoon punctatus n. sp., Thamnophis sauritus
      sackenii to Hepatozoon sauritus n. sp., and Nerodia fasciata pictiventris to
      Hepatozoon pictiventris n. sp. In Alachua County, N. fasciata pictiventris is
      parasitized by Hepatozoon fasciatae n. sp., Seminatrix p. pygaea by Hepatozoon
      seminatrici n. sp., and Thamnophis s. sirtalis by Hepatozoon sirtalis n. sp. Each
      Hepatozoon sp. has distinctive gamonts and sporogonic characters and, in the 4
      species where known, meronts. Nerodia floridana is host to Haemogregarina
      floridana n. sp. in both localities, with generic identification tentative, based
      upon presence of erythrocytic meronts. The presence of sporocysts in the
      proboscis of 31% of Aedes aegypti infected by H. pictiventris is the first report
      of infective stages of a reptilian Hepatozoon species within the mouthparts of a
      dipteran vector. This study suggests that in Florida, at least, the diversity of
      the Hepatozoon community not only equals but probably exceeds the diversity of
      the snake communities present, and that host specificity in nature may be much
      greater than that postulated from previous studies.

PMID- 11534656
TI  - Prevalence of Neospora caninum infection in dogs from beef-cattle farms, dairy
      farms, and from urban areas of Argentina.
AB  - Prevalence of anti-Neospora caninum antibodies was determined in sera of 320 dogs
      from Argentina using the indirect fluorescent antibody test (IFAT). Antibodies to
      N. caninum were found in 121 of 320 (37.8%) sera with titers of 1:50 (21 dogs),
      1:100 (23 dogs), 1:200 (23 dogs), 1:400 (17 dogs), 1:800 (23 dogs), and > or =
      1:1.600 (14 dogs). The seropositivity (IFAT, > or = 1:50) was higher in dogs from
      dairy (48% of 125) and beef (54.2% of 35) farms than in dogs from urban areas
      (26.2% of 160). Prevalence of anti-N. caninum antibodies was higher in dogs more
      than 12 mo of age (47.7%, 105 of 222) versus in 12-mo-old or younger dogs (12.7%
      of 86), suggesting postnatal exposure of N. caninum infection in dogs.

PMID- 11534657
TI  - Monogeneans in introduced and native cichlids in Mexico: evidence for transfer.
AB  - We examined 2 cichlid fish species native to Mexico, Cichlasoma callolepis and C.
      fenestratum, and 2 introduced African cichlids, Oreochromis aureus and O.
      niloticus, from 3 localities in southeastern Mexico for monogeneans. Six
      monogenean species infected the African cichlids: Cichlidogyrus haplochromii, C.
      dossoui, C. longicornis longicornis, C. sclerosus, C. tilapiae, and Enterogyrus
      malmbergi. We found all these parasite species, except C. haplochromii and C.
      dossoui, on the native C. fenestratum and C. callolepis. Prevalences of
      Cichlidogyrus spp. were 3-10% and abundances ranged from 0.03 +/- 0.2 to 0.1 +/-
      0.3 for native cichlids. We only recovered a single E. malmbergi from 1 C.
      callolepis. We found Sciadicleithrum bravohollisae, a monogenean of native
      Cichlasoma spp., on the gills of the introduced O. aureus from Lake Catemaco
      (prevalence 3%, abundance 0.03 +/- 0.2). Although prevalence and abundance in
      atypical hosts were fairly low, the present findings provide evidence of
      monogenean transfer from African to American cichlids and vice versa. This is the
      first record of exotic monogeneans in the genus Cichlidogyrus and Enterogyrus
      infecting native American cichlid fish. It is also the first record from
      southeastern Mexico of a native American monogenean infecting introduced African
      cichlids.

PMID- 11534658
TI  - Oocyst excretion in dogs fed mouse brains containing tissue cysts of a cloned
      line of Neospora caninum.
AB  - Neospora caninum is an apicomplexan parasite that causes neonatal neuromuscular
      disease in dogs and abortions in cattle. Bovine neosporosis is a major production
      problem worldwide. The parasite is transmitted to cattle via oocysts excreted by
      dogs or by transplacental transmission. Dogs are the only proven definitive host
      for N. caninum. One of 3 dogs fed mouse brains containing tissue cysts of a wild
      type N. caninum strain CK0160SC3B (CKO) excreted oocysts in its feces. Two of 3
      dogs fed mouse brains containing tissue cysts from a cloned line of the CKO
      strain excreted N. caninum oocysts in their feces. The results indicate that a
      single N. caninum tachyzoite contains all the genetic information needed to
      produce the asexual and sexual cycles in the canine intestine.

PMID- 11534659
TI  - Contemporaneous and successive mixed Plasmodium falciparum and Plasmodium vivax
      infections are associated with Ascaris lumbricoides: an immunomodulating effect?
AB  - Following an investigation suggesting a protective role for Ascaris against
      cerebral malaria, possibly through immunomodulation, we examined whether Ascaris
      had any impact on mixed Plasmodium falciparum and Plasmodium vivax infections. We
      studied a cross section of 928 patient files between 1991 and 1999. Forty
      patients had contemporaneous mixed infections and 40 patients had P. falciparum
      infections, followed by P. vivax infections. There was a significant association
      between Ascaris infection and risk of having both contemporaneous or successive
      mixed P. falciparum and P. vivax infections (adjusted odds ratios respectively 6
      [2-18] P = 0.001 and 3.6 [1.2-11.1] P = 0.02). There was a positive linear trend
      between the burden of Ascaris and the risk of mixed infections P < 0.0001. These
      results suggested the possibility that pre-existing Ascaris infection may
      increase tolerance of the host to different Plasmodium spp., thus facilitating
      their coexistence.

PMID- 11534661
TI  - Analysis of responses of Leidynema appendiculata to acetylcholine using
      electrophysiological techniques.
AB  - The electrophysiological responses of adult females of the insect-parasitic
      nematode Leidynema appendiculata, to 100 mM, 10 mM, and 1 mM acetylcholine were
      concentration dependent, with stimulation by 100 mM acetylcholine giving the
      largest increase in spike activity. By contrast, the delay in response was not
      concentration dependent. No increase in activity was obtained on stimulation with
      either 0.1 mM acetylcholine or phosphate-buffered saline. The lack of response to
      0.1 mM acetylcholine was confirmed by sequential exposure of L. appendiculata to
      0.1 mM acetylcholine and subsequently to 10 mM acetylcholine.

PMID- 11534660
TI  - The salivary adenosine/AMP content of Phlebotomus argentipes Annandale and
      Brunetti, the main vector of human kala-azar.
AB  - Adenosine and AMP in the salivary glands of the sand fly Phlebotomus argentipes
      were characterized by reversed-phase high-pressure liquid chromatography with
      diode-array detection and mass spectrometry. AMP and adenosine were measured in
      individual salivary gland pairs, yielding 76.8 +/- 8.6 and 380 +/- 25 pmoles per
      pair of salivary glands, respectively (mean +/- SE, n = 12). These values
      decrease to 45 +/- 7 and 181 +/- 21 pmoles following a blood meal, indicating
      that AMP and adenosine were secreted. Because adenosine and AMP have anti
      platelet, vasodilatory, and immunomodulatory properties, it is proposed that
      these salivary nucleotides help the fly to blood feed and may affect Leishmania
      transmission.

PMID- 11534662
TI  - Mg2+, Mn2+, and Co2+ stimulate Entamoeba histolytica to produce chitin-like
      material.
AB  - The mechanism of Entamoeba histolytica cyst cell wall synthesis is not well
      understood. Previous research has shown that cyst-like structures formed in the
      presence of chitin synthase cofactors (Mg2+, Mn2+, and Co2+) resist 1% sodium
      dodecyl sulfate lysis (RCLS), whereas those formed in the absence of cofactors
      (CLS) do not, and trophozoites are immediately destroyed. This suggests that E.
      histolytica is able to synthesize chitin, initiating a differentiation process
      under axenic conditions. To test this hypothesis, polysaccharide hydrolysates
      from E. histolytica trophozoites, CLS, or RCLS were analyzed with high
      performance liquid chromatography. The major components found in all 3
      preparations were N-acetylglucosamine (NAG) and glucose (GLC), with RCLS
      possessing 129 and 180 times more NAG and 2.4 and 2.0 more GLC than trophozoites
      and CLS, respectively. After 36 hr of incubation with chitinase (16 U/ml) in a
      hypotonic medium (50 mOsm/kg), 68% of RCLS was lysed, and 100% lost affinity for
      calcofluor white M2R. The RCLS polysaccharides bound wheat germ agglutinin and
      appeared as long and thin or short and thick fibers. Accordingly, Mg2+, Mn2+, and
      Co2+ stimulated E. histolytica to synthesize a chitin-like material.

PMID- 11534663
TI  - Behavior of atrial natriuretic factor in an experimental model of Trypanosoma
      cruzi infection in rats.
AB  - Enhanced atrial natriuretic factor (ANF) production by the heart is related to
      hemodynamic overload, cardiac growth, and hypertrophy. The heart is one of the
      most affected organs during Trypanosoma cruzi infection. We tested the hypothesis
      that myocarditis produced by parasite infection alters the natriuretic peptide
      system by investigating the behavior of plasma ANF during the acute and chronic
      stages of T. cruzi infection in rats. Sprague-Dawley rats were infected with T.
      cruzi clone Sylvio-X10/7. Cardiac morphology showed damage to myocardial cells
      and lymphocyte infiltration in the acute phase; and fibrosis and cell atrophy in
      the chronic period. Plasma ANF levels (radioimmunoassay) were significantly
      higher in acute (348 +/- 40 vs. 195 +/- 36 pg/ml, P < 0.05, n = 17) and chronic
      T. cruzi myocarditis (545 +/- 81 vs. 229 +/- 38 pg/ml, P < 0.001, n = 11) than in
      their respective controls (n = 10 and 14). Rats in the chronic phase also showed
      higher levels than rats in the acute phase (P < 0.01). The damage of myocardial
      cells produced by the parasite and the subsequent inflammatory response could be
      responsible for the elevation of plasma ANF during the acute period of T. cruzi
      infection. The highest plasma ANF levels found in chronically infected rats could
      be derived from the progressive failure of cardiac function.

PMID- 11534664
TI  - Identity of Cysticercoides menidiae Chandler, 1935 (Cestoda: Dilepididae).
AB  - Cysticercoides menidiae Chandler, 1935, described as a metacestode of an unknown
      dilepidid cestode from the intestinal wall and mesenteries of the silversides
      Menidia menidia (Pisces: Atherinidae), from Galveston Bay, Texas, was found to be
      conspecific with Ascodilepis transfuga (Krabbe, 1869), a tapeworm described from
      the spoonbill. Platalea ajaja Linnaeus (syn. Ajaja ajaja), from Brazil.
      Consequently. C. menidiae becomes a junior synonym of A. transfuga.

PMID- 11534665
TI  - Development of a method for the in vitro production of Plasmodium vivax
      ookinetes.
AB  - We developed a method for the in vitro production of mature Plasmodium vivax
      ookinetes. Gametocytemic blood was collected from 98 P. vivax-infected patients
      reporting to malaria clinics in Maesod and Maekasa Districts, Tak Province,
      Thailand. Briefly, gametogenesis was induced using xanthurenic acid and parasites
      were separated by density gradient centrifugation and then cultured in RPMI-1640,
      pH 7.8-8.2. At the same time that blood was collected, 200 Anopheles dirus
      mosquitoes were allowed to feed on each patient. Mosquito midguts were removed 2
      36 hr postfeeding, and gut contents were smeared onto glass slides, as were
      cultured samples from varying time points. Slides were stained with Giemsa, and
      the in vitro and mosquito development of ookinetes compared. Mature ookinetes
      were produced in 48.0% (47/98) of in vitro cultures, with a total yield ranging
      from 10 to 248,500 (mean = 15,523, median = 600) ookinetes produced per 5 ml
      blood. The temporal development and the morphology of the P. vivax ookinetes
      produced in vitro was similar to that observed in the A. dirus mosquitoes. The
      method that we describe is simple, can be used at remote sites without
      sophisticated equipment, and yields high numbers of clean ookinetes. This method
      of producing mature P. vivax ookinetes will be a useful tool for studies on
      ookinetes in P. vivax endemic regions.

PMID- 11534666
TI  - A comparison of the blood parasites in three subspecies of the yellow wagtail
      Motacilla flava.
AB  - One-hundred and eighty yellow wagtails Motacilla flava belonging to 3 subspecies
      (Motacilla flava feldegg, Motacilla flava flava, Motacilla flava thunbergi) were
      caught during the spring migration in south Kazakhstan and investigated by
      microscopic examination of stained blood smears. Haemoproteus anthi, Haemoproteus
      motacillae, Leucocytozoon fringillinarum, Leucocytozoon majoris, Plasmodium
      relictum, Plasmodium polare, Atoxoplasma sp., Trypanosoma sp., and microfilariae
      were identified. The overall prevalence of infection was 47.8%. Prevalences of
      Haemoproteus spp. (27.2%), Plasmodium spp. (25.0%), Leucocytozoon spp. (8.9%),
      Atoxoplasma spp. (4.4%), Trypanosoma spp. (1.1%), and microfilariae (0.6%) were
      recorded. No differences were discernible in parasite fauna or intensities of
      infection between males and females or between different subspecies. However,
      prevalence of infection of Haemoproteus, Leucocytozoon, and Plasmodium spp. was
      different in different host subspecies. These differences can be explained by
      differences in geographical location of breeding areas of these birds.

PMID- 11534667
TI  - Identification of Sarcocystis hominis-like (Protozoa: Sarcocystidae) cyst in
      water buffalo (Bubalus bubalis) based on 18S rRNA gene sequences.
AB  - DNA templates were extracted from isolates of Sarcocystis hominis-like cysts
      collected from cattle and water buffalo, as well as from Sarcocystis fusiformis
      cysts and Sarcocystis suihominis cysts. The 18S rRNA genes were amplified using
      DNA from a single cyst as the templates. Approximately 1,367-1,440 bp sequences
      were obtained. The sequence difference in isolates of Sarcocystis hominis-like
      cysts from water buffaloes, and isolates of S. hominis cysts from cattle were
      very low, only about 0.1%, much lower than the lowest value (1.7%) among
      different species. Combined with their morphological structure, these sequence
      data indicate that the 4 isolates from cattle and water buffalo might be the same
      species, i.e., S. hominis, suggesting that both cattle and water buffalo may
      serve as the intermediate hosts for this parasite. Apparently, this is the first
      report using a single cyst to do such work and is a useful way to distinguish the
      Sarcocystis cyst in an intermediate host that may be simultaneously infected by
      several different Sarcocystis species.

PMID- 11534668
TI  - Sarcocystis miescheriana infection in domestic pigs (Sus scrofa) in the
      Philippines.
AB  - Sarcocystis miescheriana sarcocysts were identified in skeletal muscles of 9
      (27%) of 33 swine slaughtered for human consumption. Sarcocysts were 144-180
      microm x 20-38 microm in size. Ultrastructurally, the cyst wall resembled the
      type 10 sarcocyst wall. The villar protrusions (VP) were 3-4.5 microm long and
      0.6-1.2 microm wide and had prominent longitudinally arranged microtubules
      extending from the VP tips to the granular layer (=ground substance). The
      parasitophorous vacuolar membrane with its underlying electron-dense layer (EDL)
      measured 25 nm in thickness. The base of the VP exhibited minute (0.42-0.87
      microm) bulblike inpocketings. Each VP had 80-90 microtubules situated underneath
      the EDL. The granular layer was 0.5-1.2 microm thick, and contained hairlike
      microtubules continuous with those of the VP core. This is the first report of S.
      miescheriana in Philippine domestic pigs Sus scrofa.

PMID- 11534669
TI  - The effect of hair on infection after cranial surgery.
AB  - OBJECTIVE: Reports of large series of patients who had undergone successful
      cranial neurosurgery without hair removal led part of our team to abandon the
      practice of shaving patients' heads pre-operatively. The aim of this study was to
      assess whether this change in routine, which was implemented in 1992, has
      affected the rate of postoperative infection in our cranial surgery patients.
      METHODS: A group of patients whose heads were shaved pre-operatively was compared
      to a group whose hair was not shaved prior to cranial surgery. The latter
      patients had their hair washed with shampoo and 4% chlorhexidine within 24 hours
      of their operation. In the operating room, the surgical site was scrubbed for 8
      10 minutes with 4% chlorhexidine diluted with water, and then cleansed with 10%
      povidone-iodine solution. Prophylactic antibiotics were administered for 3 days.
      RESULTS: We performed 1,038 cranial procedures without hair removal. The
      procedures included craniotomy for tumour, trauma, aneurysm, other vascular
      lesions and intracerebral haemorrhage (n = 847), stereotactic biopsy (n = 90),
      stereotactic craniotomy (n = 34), ventriculoperitoneal shunt placement (n = 27),
      surgical treatment of infection with aspiration of brain abscess or resection of
      infected tissue (n = 14), microvascular decompression for trigeminal neuralgia or
      hemifacial spasm (n = 11), and other miscellaneous procedures (n = 15). We
      observed 13 postoperative wound infections (1.25%), including 9 deep (0.87%) and
      4 superficial infections (0.39%). There was no significant difference between the
      rate of infection in patients whose heads were shaven (12/980) and the rate in
      those whose hair was spared (13/1038) (p > 0.05). In addition. there were no
      other problems related to the surgical preparation technique in the latter group.
      CONCLUSION: Cranial surgery without hair removal is safe and does not increase
      the risk of surgical wound infection. Patients naturally prefer to keep their
      full head of hair. We believe that preoperative hair removal is not necessary in
      preparation for any type of cranial neurosurgery.

PMID- 11534670
TI  - The risk of haemorrhage after image guided stereotactic biopsy of intra-axial
      brain tumours--a prospective study.
AB  - OBJECTIVE: To analyze prospectively the frequency and the risk of symptomatic and
      asymptomatic haemorrhage after image guided stereotactic biopsy of intra-axial
      brain tumours. METHODS: The study was conducted within a time frame of 24 months
      (April 1998-April 2000). 326 patients (150 males, 176 females; mean age 56.8
      years) were included and 345 computerized tomography (CT)-guided stereotactic
      biopsies were performed/supervised by a specialized stereotactic neurosurgeon. A
      modified Riechert Stereotaxy System and a workstation for multiplanar trajectory
      planning were used in all patients. Serial biopsies (median, 5 samples) were done
      with small forceps (diameter 1 mm), smear preparations of the biopsy specimens
      were intra-operatively examined. Frequency, size, and location of any detectable
      bleeding were analyzed by post-biopsy CT-scan investigation. For risk estimation,
      logistic regression analysis was performed. The chi-square statistic was used for
      comparative analysis of the study results with available data from the
      literature. RESULTS: A conclusive tissue diagnosis could be achieved in 98%.
      Overall treatment morbidity was 3.1%. There was no mortality. Haemorrhage related
      morbidity was 0.9%. Age, Karnofsky score, mass effect of the tumour, tumour
      histology, tumour location and the number of specimens taken did not have any
      prognostic significance. The clinically silent bleeding rate was 9.6% and more
      often seen in patients with high grade gliomas (p = 0.03). Both the silent and
      non-silent bleeding rate were significantly lower as compared to available
      prospective data in the literature (p < 0.01). CONCLUSION: Using multiplanar
      image guided trajectory planning, small biopsy forceps and intra-operative smear
      preparations the risk of major haemorrhage related morbidity after stereotactic
      brain tumour biopsy is extremely low (<1%) in experienced hands.

PMID- 11534671
TI  - Quality of life in patients after meningioma resection.
AB  - OBJECTIVES: To evaluate quality of life in patients after tumour resection, to
      assess different dimensions of quality of life, to compare a newly designed
      questionnaire with the Nottingham Health Profile. SUBJECTIVE: A non-selected
      neurosurgically treated series of patients with meningiomas was investigated with
      reference to quality of life as a judgement of one's own needs and concerns and
      subjective disease dependent perception. METHODS: A postal survey was sent out to
      155 patients who underwent resection of a meningioma between 1977 and 1993 at our
      clinic. The survey consisted of the specifically designed "Innsbruck Health
      Dimensions Questionnaire for Neurosurgical Patients" IHD(NS) and the Nottingham
      Health Profile NHP. The data were put into categories and analysed statistically
      (Chi-square, Mann Whitney U, Kruaskal-Wallis H-tests). RESULTS: 82 patients (53
      female, 29 male) responded (response rate 59%). 10 had died and 7 had moved. The
      majority of patients (50/61% on NHP and 49/59.7% on IHD) had mild to moderate
      impairment of quality of life. 20% of the patients showed moderate to severe
      impairment of the dimensions: physical handicap and energy level. Physical
      impairment correlated to tumour size. This group was characterised by mainly
      belonging to the over 70ies age group and taking anti-epileptics. CONCLUSIONS:
      The quality of life impairments in most patients after tumour resection can be
      classified as mild to moderate. However, other disease and age effects are
      difficult to distinguish without a control group. The IHD(NS) correlated well
      with the NHP questionnaire.

PMID- 11534672
TI  - Aggressive surgery and focal radiation in the management of meningiomas of the
      skull base: preservation of function with maintenance of local control.
AB  - BACKGROUND: Recent study series have reported that post-operative external beam
      radiation therapy and stereotactic radiosurgery with the linear accelerator or
      gamma knife improves long-term local control of subtotally resected or recurrent
      meningiomas. METHODS: Analysis of treatment results in 100 consecutive patients
      with skull base meningiomas managed by one surgeon with a median follow-up of
      five years. Treatment principles included observation for asymptomatic tumors;
      surgery for progressive or symptomatic tumors unless surgery was medically
      contraindicated or refused by the patient; to make surgery as aggressive as
      possible but with the goal of preserving full function of the patient; and to use
      radiosurgery or conformal fractionated radiation therapy if residual tumor was
      demonstrated. Preoperative, postoperative, and observational data were
      prospectively accumulated and stored in a large database system. Median follow up
      was 5 years with a range from 2 to 10 years. FINDINGS: The most frequent
      presenting symptoms were headache (45%) and changes in vision (29%). Cranial
      nerve deficits (49%) and cerebellar signs (24%) were the most common physical
      findings. Seventy-two patients had surgical resection. Of these, 93% had greater
      than 50% resection and 47% had radiographically complete resection. There were no
      perioperative deaths and there were five surgical complications for a rate of 7%.
      Complications included hemiparesis (2.8%), new cranial nerve palsy (2.8%), and
      indolent osteomyelitis (1.4%). Fifteen patients had observation only; none of who
      progressed. Thirteen patients had radiation only, primarily because of patient
      preference or medical contraindications to surgery in the setting of substantial
      symptoms. There were no complications of this therapy. With a median five-year
      follow-up, only one patient (1%) demonstrated tumor progression using the
      treatment paradigm outlined here. INTERPRETATION: These results demonstrate that
      skull base meningiomas which require treatment can be managed with a combination
      of aggressive surgery and conformal radiation with an acceptable functional
      status in 99% of cases.

PMID- 11534673
TI  - Tamoxifen sensitivity-testing of glioblastomas: comparison of in vitro and in
      vivo results.
AB  - BACKGROUND: Only less than half of the patients with malignant gliomas respond to
      a continuous high dose Tamoxifen (TAM) and/or Carboplatin (CP)-treatment.
      Therefore, a method for predicting the efficacy of TAM-treatment would be
      desirable. METHODS: Paralleling a clinical study, the predictive value of in
      vitro-sensitivity testing of TAM and TAM's metabolite 4-OH-TAM in primary
      cultures of tumour explants from 15 of a total of 50 patients was examined.
      Additionally, the influence of TAM, 4-OH-TAM, and CP on the proliferation of
      established glioblastoma cell lines and of those explanted from athymic nude mice
      and re-established in cell culture was investigated. Human glioblastomas
      xenotransplanted subcutaneously into athymic nude mice and subsequently treated
      with TAM and/or CP were examined in a parallel in vivo-study. FINDINGS: TAM
      chemosensitivity-testing of glioblastomas failed to predict the clinical response
      to TAM-treatment in our patients and did not correlate with the in vivo-TAM
      response of tumours xenotransplanted into nude mice. TAM's and 4-OH-TAM's ability
      to inhibit growth of various glioblastoma cell lines in vitro in very similar
      concentrations was shown to be a consistent phenomenon which seems to be
      independent of the in vivo response in either patients or mice as previous hosts.
      However, CP's antiproliferative effect on glioblastomas in vivo was paralleled by
      respective in vitro results. Whereas TAM showed to mediate its in vitro
      antiproliferative effect by inducing apoptosis in most cell lines examined, CP
      treatment lead to necrosis of cells. INTERPRETATION: Combining the results
      obtained from our human and mouse studies, it has to be postulated that host
      factors other than the sensitivity to TAM of the individual cell, determine the
      efficacy of TAM-treatment in vivo.

PMID- 11534674
TI  - Intracranial hemangiopericytoma: study of 12 cases.
AB  - Most hemangiopericytomas (HPCs) are located in the musculoskeletal system and the
      skin, while the intracranial location is rare. They represent 2 to 4% in large
      series of meningeal tumours, thus accounting for less than 1% of all intracranial
      tumours. Many authors have argued about the true origin of this tumour. The
      current World Health Organization classification of Central Nervous System
      tumours distinguishes HPC as an entity of its own, and classified it into the
      group of "mesenchymal, non-meningothelial tumours". Radical surgery is the
      treatment of choice, but must be completed with postoperative radiotherapy, which
      has proved to be the therapy most strongly related to the final prognosis. HPCs
      have a relentless tendency for local recurrence and metastases outside the
      central nervous system which can appear even many years after diagnosis and
      adequate treatment of the primary tumour. Twelve patients with intracranial HPC
      were treated at our Unit between 1978 and 1999. There were 10 women and 2 men.
      Ten tumours were supratentorial and most located at frontoparietal parasagittal
      level. The most common manner of presentation was a focal motor deficit. All
      tumours were hyperdense in the basal Computed Tomography scans and most enhanced
      homogeneously following intravenous contrast injection. In 50% of cases, tumour
      margins were irregular or lobulated. Seven tumours were studied with Magnetic
      Resonance Imaging, being six of them iso-intense with the cortical gray matter on
      T1-weighted and T2-weighted images. Twenty operations were performed in the 12
      patients. In 10 cases radical excision could be achieved with no operative
      mortality. Total recurrence rate was 33.3%. Eight patients were treated with
      external radiotherapy at some time through the course of their disease. Eight out
      of the 12 patients in this series are disease-free (Glasgow Outcome Scale
      categories 1 and 2) after a mean follow up of 52 months.

PMID- 11534675
TI  - Acoustic neurinomas during pregnancy: report of two cases and review of
      literature.
AB  - Though infrequent, acoustic neurinomas have been described during pregnancy and
      represent a therapeutic challenge for excision without producing any problem for
      the mother and the foetus. First Author experienced two cases of acoustic
      neurinomas presenting during pregnancy. One patient presented in the terminal
      stages of the third trimester of pregnancy and underwent caesarean section,
      followed by retromastoid craniectomy and excision of the tumour. Operative
      management of the pregnancy and tumour in the same sitting has not been reported
      in the literature. Second patient who presented during 2nd trimester of
      pregnancy, was operated on for the tumour and had a successful continuance of
      pregnancy. Details of the management are discussed and the relevant literature
      reviewed. In addition to causing aggravation of symptoms, the larger size and
      increased vascularity of these tumours during pregnancy, makes them more
      vulnerable to acute bleeding, which in turn may initiate new or exacerbate pre
      existing symptoms, as noted in one of the cases presented in this report.

PMID- 11534676
TI  - Accuracy of stereotactic localisation with magnetic resonance compared to CT
      scan: experimental findings.
AB  - BACKGROUND: Stereotactic localisation of proper targets can be obtained with
      Magnetic Resonance imaging (MRI), pending correction of the well-known inaccuracy
      of MRI in reproducing exact geometrical dimension. The aim of the experimental
      work was to determine the real extent of the MRI distortion and to correct it.
      METHODS: PVC phantoms and fixed human brains were used as target simulators:
      stereotactic targeting was obtained with CT and MRI: the results were compared
      and, finally, the real stereotactic values were measured on a commercial
      stereotactic device. To optimise MRI targeting it was necessary to abate the
      "chemical-shift", to modify the head-coil receiver (tuning the "off-resonance"
      frequencies) and to correct the targeting directly on the images (especially for
      the Y axis values); careful quality control and environmental tests were also
      necessary to maintain good performances along the time. RESULTS: 172 measurements
      were carried out using both CT, plain X-ray and MRI on PVC phantom. The values
      obtained from CT were considered as reference. Significant geometrical accuracy
      was found with CT targeting, except for the Z co-ordinate, due to the slice
      thickness. Mean value differences between the targets on MRI and their real
      geometric position are about 1 mm on X and Z axises and about 2 mm on Y axis.
      Similar results were obtained on fixed brains, where absolute values of X and Y
      co-ordinates of the simulators were measured using a millimetre grid placed over
      the brain slice. INTERPRETATION: Experimental findings concerning stereotactic
      targeting with MRI suggest accuracy adequate for clinical practice, even when
      extreme geometrical precision is required, such as in radiosurgery or functional
      stereotaxy. Careful quality control and intensive experimental setting of the MRI
      device are mandatory to obtain satisfactory results.

PMID- 11534677
TI  - Vertical displacement of the brain and the target area during open stereotaxic
      neurosurgery.
AB  - During stereotaxic thalamotomies, we observed that the brain surface was sinking.
      The study was carried out to investigate to what extent the target area also was
      displaced and how this would affect the accuracy of the stereotaxic procedure. In
      12 thalamotomies, with the patients operated on in the sitting position, we found
      that the cortical surface sank 0-9 (mean 5) mm during the operation. The vertical
      co-ordinate of the thalamic target was consequently adjusted per-operatively, and
      the electrodes were advanced an additional distance of 1-5.5 (mean 3.5) mm in an
      attempt to compensate for the assumed sinking of the target. This per-operative
      adjustment was based on the surgeon's experience and the results of macro
      stimulation studies. The exact location of the thalamotomy lesion, and thereby
      the accuracy of the adjustment, was evaluated on 3 months postoperative CT scans.
      These showed that the intended target was hit with a sufficient degree of
      accuracy in all the patients, although the vertical co-ordinate had been slightly
      over-adjusted, as the center of the lesion on the average was located 1 mm below
      the intended location. Thus, if the vertical position had not been adjusted, the
      lesion would on the average have been located 2.5 mm too high compared with the
      intended target. Patients undergoing thalamotomy and other stereotaxic
      procedures, where a high degree of accuracy is needed, should be operated on in
      the sitting position. At the thalamic level, the vertical displacement of the
      target should be adjusted for by additional advancement of the stereotaxic probe.
      On average, this compensatory adjustment should be about half the per-operative
      sinking of the cortical surface.

PMID- 11534678
TI  - Eight year outcome after surgery for lumbar disc herniation: a comparison of
      reoperated and not reoperated patients.
AB  - A retrospective study of 211 patients with unilateral sciatica operated on for
      lumbar disc herniation during 1988 and 1989 was performed in order to compare the
      results of reoperated patients with the results of patients operated on only
      once. The patients completed a standardized questionnaire in 1997 which included
      questions about reoperations, back and leg pain, functional status and disability
      pension. Outcome scores were calculated, giving values from 0 (no pain/normal
      function) to 100 (totally disabled). A follow-up status of 80.1% was obtained;
      163 patients answered the questionnaire while six patients had died. 23.9% of the
      patients (n = 39) had been reoperated on. A recurrent disc herniation at the same
      level was suspected before the reoperation in 18.4%, but a recurrence was found
      in only 8.6%. 3.7% were reoperated on more than once. Outcome score was worse
      among "reoperated" patients (median 45.0, range 0-94) than among patients who
      only had the primary operation (median 10.5, range 0-81) (P < 0.001). In
      addition, 34.3% of the "reoperated" patients received a disability pension
      compared to 9.9% of the patients not reoperated on (P < 0.01). Patients
      reoperated upon at the same level without peroperative signs of recurrent disc
      herniation, had an outcome score of 53.0 (range 0-82) compared to a score of 30.0
      (range 0-66) in patients with a confirmed recurrence (P < 0.05). The percentage
      of disability pension was 53.8% versus 9.1%, respectively, for those two groups
      (P < 0.05). Eight years after operation for lumbar disc herniation, the outcome
      was significantly worse in "reoperated" patients than in patients operated on
      once. In addition, reoperated patients with peroperatively confirmed recurrence
      of the same disc, seemed to have a better outcome than patients without
      peroperative signs of a recurrence.

PMID- 11534679
TI  - Surgical treatment of chronic subdural hematoma based on intrahematomal membrane
      structure on MRI.
AB  - BACKGROUND: To determine the optimal surgical management of chronic subdural
      hematoma (CSDH), we assessed which operative procedure, burr holes or small
      craniotomy, was more effective on 49 consecutive patients. METHOD: We
      retrospectively classified all cases into two groups according to the
      intrahematomal membrane structure of CSDH on T2*-weighted magnetic resonance (MR)
      imaging. The first group, labeled type B, included hematomas which had no
      intrahematomal membrane and/or were monolayer multilobule. The second group,
      labeled type C, consisted of hematomas which were divided into multiple layers by
      the intrahematomal membrane. FINDINGS: The outcome of type C patients treated
      with burr holes was significantly inferior to that of those who underwent a small
      craniotomy in terms of the relative outcome of neurological grading. re-operation
      ratio, and postoperative hospital stay (p < 0.05). Type C hematomas treated with
      burr holes also had inferior outcome compared with a small craniotomy in terms of
      the duration of hematoma until disappearance on postoperative CT (p < 0.05).
      INTERPRETATION: We concluded that a considerable number of cases appeared to need
      craniotomy and resection of intrahematomal membrane for complete recovery in
      CSDH, and that T2*-weighted MR imaging could be used as a basis for selecting the
      operative procedure for CSDH.

PMID- 11534680
TI  - The influence of intra-operative brain shift on continuous cortical stimulation
      during surgery in the motor cortex--an illustrative case report.

PMID- 11534681
TI  - Intracerebral haematomas with agenesis of the internal carotid artery and
      tetralogy of Fallot.
AB  - We report a rare case with tetralogy of Fallot (TOF) and agenesis of the internal
      carotid artery (ICA) who presented serious intracerebral haematomas. In the
      literature, this is the first documented case having these complications
      simultaneously. Extreme hypoxic insults followed by recovery were detected by O2
      saturation monitor before two bleeds. Chronic brain hypoxia could make the
      vasculature weak, which was shown in the histological examination. A 2-year-old
      girl was transferred to us with a general convulsion due to intracerebral
      haematoma. She had been showing general cyanosis from birth due to TOF. Repeated
      intracerebral haemorrhages ended her life. Histological study showed dilated
      vascular channels in the subarachnoid space and necrotizing vasculature
      obstructed by fibrinous thrombi adjacent to the haematoma. Fibrosis of the vessel
      wall with infiltration of macrophages suggested subacute or chronic lesions
      rather than acute necrosis due to the multiple haemorrhages. The intracerebral
      haematomas and agenesis of the ICA were observed as unilateral hemispheric
      vascular complications of TOF. Chronic brain hypoxia could play an important role
      in weakening the vessel wall and erythrocytosis caused obstructing thrombi. We
      speculate these factors generated the intracerebral haematomas.

PMID- 11534682
TI  - Acute foot drop caused by thrombosed epidural vein.

PMID- 11534683
TI  - Surgical treatment of noncontiguous spinal metastases and plasmacytomas.

PMID- 11534684
TI  - Flow quantification of the non-occlusive excimer laser-assisted EC-IC bypass.
AB  - BACKGROUND: For six years, we used the Excimer laser-assisted nonocclusive
      anastomosis technique for high-flow revascularization of the brain in patients
      with either nonclippable and noncoilable giant aneurysms of the internal carotid
      or basilar artery or progressive stroke associated with occlusive disease of the
      internal carotid artery. The aim of this study is to assess the blood flow
      capacity of this type of Extra-Intracranial bypass and its haemodynamic behaviour
      over time. METHODS: Twenty-six patients with a giant aneurysms and 8 patients
      with occlusive disease of the internal carotid artery were treated with the
      nonocclusive Excimer laser assisted EC-IC bypass. intra-operatively, direct
      measurements of flow in the EC-IC bypass were performed in all patients
      (Transonic Systems, Inc., Ithaca. NY). Postoperatively, follow up measurements of
      flow were performed with MR angiography in 14 patients with a giant aneurysm
      after occluding the internal carotid artery, and 7 patients with occlusive
      carotid disease. RESULTS: The mean flow in the laser assisted bypasses in the
      group of patients with a giant aneurysm was 158 ml/min after ligation or balloon
      occlusion of the ICA. The mean flow of the laser assisted bypass in the group of
      patients with ICA occlusive disease was 130 ml/min. A comparison with data on
      flow capacity of conventional EC IC bypasses is made. A demonstrated increase of
      flow in the bypass during follow up is discussed from a haemodynamic point of
      view. CONCLUSIONS: The results of this study demonstrate that the flow capacity
      of the nonoccluding excimer laser assisted bypass is much higher than the
      capacity of the conventional, more peripherally located conventional EC IC
      bypass, and should therefore be denoted as High-Flow EC IC bypass. Consequently,
      this type of bypass can be a powerful and safe tool in new revascularization
      strategies.

PMID- 11534685
TI  - Results of direct surgery for aneurysmal subarachnoid haemorrhage: outcome of
      2055 patients who underwent direct aneurysm surgery and profile of ruptured
      intracranial aneurysms.
AB  - BACKGROUND AND PURPOSE: The purpose of this study is to evaluate the therapeutic
      value of our surgical treatment of subarachnoid haemorrhage in a large series
      with standardized surgical principles. METHODS: Results of 2055 direct operations
      on ruptured intracranial aneurysms, treated in our institutions, where surgical
      indications, instruments and techniques were standardized, between 1988 and 1998,
      were retrospectively evaluated and outcome of the patients was discussed; cases
      treated by intravascular procedures were excluded. RESULTS: According to the
      evaluation at discharge, 1083 (52.7%) patients were excellent, 324 (15.8%) good
      and 223 (10.9%) fair. There were 160 (7.8%) patients of poor outcome and the
      remaining 265 (12.9%) died. There were no differences in the outcome between pre
      operative Hunt & Kosnik grade I and II, Fisher Scale 1 and 2, anterior
      circulation aneurysms and posterior circulation aneurysms except those at and
      around the basilar bifurcation, men and women, and those clipped and not clipped.
      CONCLUSIONS: The factors related to poor outcomes were, age of 60 years or over,
      pre-operative Hunt & Kosnik grade II or more, Fisher Scale 3 or more, aneurysm
      size over 15 mm in diameter, and location at and around the basilar artery
      bifurcation. The results presented in this study show the status of our direct
      surgical management of subarachnoid haemorrhage in a large series with
      standardized surgical principles and procedures.

PMID- 11534686
TI  - Prognostic factors on hospital admission after spontaneous subarachnoid
      haemorrhage.
AB  - BACKGROUND AND OBJECTIVE: Factors related to prognosis after subarachnoid
      haemorrhage (SAH) have been mainly extracted from surgical series, and only few
      authors have considered these factors in total management or population series.
      Though the level of consciousness is a major determinant of outcome after
      subarachnoid haemorrhage, there is not a consensus about which classification
      should be used to define it. The objective of this study was twofold. Firstly to
      find which factors recorded on hospital admission relate to outcome determining
      their relative importance in a non-selected series of patients suffering from
      aneurysmal SAH admitted to our centre, and secondly to assess the validity of the
      WFNS clinical scale for predicting the final result. METHODS: A series of 294
      patients consecutively admitted to Hospital 12 de Octubre Madrid between January
      1990 and June 2000 with the diagnosis of aneurysmal SAH were retrospectively
      reviewed. All factors possibly related to prognosis were recorded on hospital
      admission. Outcome was measured by means of the Glasgow Outcome Scale measured
      one month after hospital discharge. Relationship between factors and outcome was
      evaluated by univariate and logistic regression multivariate analysis. RESULTS:
      Although several factors, appeared related to prognosis in the univariate
      analysis, only the age. the level of consciousness defined by the WFNS scale and
      the presence of global brain hypodensity on the initial CT scan had a significant
      prognostic influence in the logistic regression model. Global brain hypodensity
      was strongly related to mortality. Since a number of factors associated with poor
      outcome in the univariate analysis are related to age, their influence could be
      explained by the difficulty of recovery of the ageing brain. The WFNS grading
      scale failed to predict significant differences in outcome between some of its
      grades. CONCLUSIONS: Age and clinical grade on admission are the most important
      factors influencing the final outcome of patients suffering aneurysmal SAH. A
      reappraisal of the WFNS grading scale should be considered as no significant
      differences in outcome were found between some of its grades.

PMID- 11534687
TI  - Microsurgical management of cerebral aneurysms based in CT angiography with three
      dimensional reconstruction (3D-CTA) and without preoperative cerebral
      angiography.
AB  - OBJECTIVE: To study the possibilities of the microsurgical management of ruptured
      intracranial aneurysms with the sole preoperative information provided by
      computed tomography angiography with three-dimensional reconstruction (3D-CTA).
      METHODS: Patients were studied with 3D-CTA after diagnosis of subarachnoid
      hemorrhage. If the study had an adequate quality and revealed an aneurysm
      congruent with the clinical findings or neurological examination and/or with the
      location of the bleeding on computed tomography (CT) scan an early microsurgical
      clipping of the lesion was done. When the quality of the 3D-CTA study was not
      adequate or the quality being adequate displayed no lesions or the findings were
      not accurate enough to warrant direct microsurgical treatment, the patient was
      studied with cerebral digital subtraction (DS) angiography. A total of 44
      consecutive patients harbouring a total of 47 intracranial aneurysms diagnosed by
      3D-CTA and without preoperative DS angiography were submitted to microsurgical
      clipping and included in the study. RESULTS: The overall mortality was 15.9% and
      the favourable results evaluated 6 months after discharge by means of the Glasgow
      Outcome Scale reached 70.4%. All lesions were successfully clipped. Surgery was
      done a mean of 4.1 days after the admission bleeding. A total of four
      microlesions undiagnosed by 3D-CTA were found at surgery and clipped.
      Postoperative DS angiography and necropsy findings were also used as control of
      the 3D-CTA findings but no additional information was provided excepting the
      finding in DS angiography of an asymptomatic intracavernous aneurysm. Therefore
      the sensitivity of the 3D-CTA for diagnosis of symptomatic aneurysms was 100% and
      the overall sensitivity 90.4%. CONCLUSIONS: We have reached similar results in
      patients operated on with or without preoperative angiography. 3D-CTA provides
      very valuable anatomical information, which has an additional value in the
      microsurgical treatment of aneurysms of the anterior communicating artery
      complex. Finally, selected cases of ruptured intracranial aneurysms can be
      successfully managed with the preoperative information provided by 3D-CTA and
      without DS angiography.

PMID- 11534688
TI  - Treatment of unruptured intracranial aneurysms--a clinicopathological
      correlation.
AB  - OBJECT: Brain check-up is very important for detecting the incidence and
      prevalence of aneurysms in the population and to get the definite strategy for
      the treatment of intracranial aneurysms. METHODS: This is a retrospective study
      of 116 aneurysms detected by brain check-up between 1998-1999 which were treated
      either by clipping or endovascular coiling. In some cases the aneurysmal wall was
      resected for histopathological examination and compared with five normal autopsy
      cases. CONCLUSIONS: Direct surgery is the primary option for a patient with an
      aneurysm in the anterior circulation especially in young patients. Intravascular
      therapy is suitable for aneurysms in the posterior circulation and in
      intracavernous site.

PMID- 11534689
TI  - Gamma knife radiosurgery of acoustic neurinomas.
AB  - The authors report on their series of 40 patients with 41 acoustic neurinomas
      (ACNs), including one patient with bilateral acoustic neurinomas suffering from
      neurofibromatosis type 2 (NF II) who were treated with the gamma knife unit at
      their institution between August 1992 and October 1995. Of these 41 tumours, 21
      ACNs had been operated on before (1 to 4 times), 20 ACNs were exclusively treated
      by gamma knife radiosurgery (GKRS). The maximal axial tumour diameter ranged from
      6 to 33 mm (median: 25 mm), the maximal transverse tumour diameter ranged from 7
      mm to 36 mm (median: 16 mm). The dose distributed to the tumour margin was 10 to
      17 Gy (median: 12 Gy) by enclosing the tumour with the 40% to 95% isodose line
      (median: 50% isodose line) and using 1 to 12 isocenters (median: 5 isocenters).
      Central loss of contrast enhancement was observed in 78% of the patients within
      six to 12 months after radiosurgery. Thirty-two patients were observed over a
      minimum follow up period of at least 36 months, 9 patients were lost to follow up
      as they died of unrelated causes or refused further check-ups. Within the follow
      up period of up to seven years, magnetic resonance imaging (MRI) control scans
      revealed the tumour diameter stable or decreased in 29 cases and increased in
      three tumours. Of 14 patients with useful hearing before treatment, 9 patients
      were examined in addition to pure tone audiogramm by measurement of brainstem
      auditory evoked potentials (BAEPs) one to four years after radiosurgery. None of
      these patients showed a postoperative loss of the cochlea function. According to
      slight alterations of the cochlea function (cochlea summating action potential),
      pure tone audiometry of those patients revealed only slight changes of the
      hearing level (HL) within a maximum range of +/-15 Decibel (dB). The hearing
      threshold improved in two, was stable in four and deteriorated in three patients,
      respectively. We observed postradiosurgical aggravation of a pre-existing facial
      weakness in two out of 13 patients, a new occurrence of facial palsy was seen in
      two cases (four years after treatment), one of them was previously operated on
      and both suffered from cystic degeneration with mass effect. Tinnitus improved in
      six out of 13 patients, deteriorated in two and never appeared as a new permanent
      sequela. Trigeminal hypaesthesia did also not appear as a new permanent symptom,
      improved in three out of 9, and deteriorated in one out of 9 patients. Vertigo
      increased in six out of 23, was stable in 8 and decreased in nine out of 23
      patients each. GKRS proves to be a safe and highly satisfactory therapeutical
      option or addition to open surgery, especially for radiologically verified
      regrowing residual ACNs, but also as primary treatment in selected patients. A
      high rate of tumour control can be achieved with an acceptable rate of
      neurological deficits.

PMID- 11534690
TI  - Evolution of malignant cerebellar astrocytoma at the site of a treated
      medulloblastoma: report of two cases.
AB  - The authors report two unusual cases in which a malignant astrocytoma developed
      at the site of the excision of an earlier medulloblastoma. While the precise
      etiology of these astrocytic tumours was unproven, theories of the origins of the
      second tumours, particularly in relation to the basic nature of medulloblastomas,
      are discussed.

PMID- 11534691
TI  - Heavily T2 weighted MR assessment of fornical injury after anterior
      interhemispheric approach for large suprasellar tumors.
AB  - Fornical injury in transforaminal approach is well known. Its injury in the
      anterior interhemispheric approach (AIA) has been rarely highlighted. We report 2
      cases with a large suprasellar tumor who underwent AIA. Postoperative heavily T2
      weighted reversed (T2R) MR images demonstrated its unilateral injury. The
      clinical significance of symptom-free fornical injury after AIA is discussed.
      Cases 1 and 2 were a 15 year-old girl with a meningioma and a 49-year-old woman
      with a craniopharyngioma, respectively. They underwent AIA. Postoperative T2R
      images revealed unilateral fornical crus atrophy. They did not present associated
      memory deficits. Case 1 had the injury of both fornical column and anterior
      commissure. They were speculatively torn by intra-operative lateral retraction of
      the frontal lobes. Case 2 had unilateral atrophy of the mammillary body and
      postcommissural fornix, which were probably caused by ischemic damage related to
      surgical manipulation, since case 2 had an associated anterior thalamic infarct.
      During the operation for large suprasellar tumors, excessive laterally directed
      brain retraction should be avoided, since such manipulation may easily tear the
      overstretched anterior commissure and fornical column. Once we notice or suspect
      fornical injury on MR studies in cases of re-operation, we have to choose a
      surgical approach and operative manipulation to preserve an intact fornix. The MR
      evaluation of fornix should be included in the perioperative radiological
      assessment, since patients with unilateral fornical injury were free of memory
      disturbance, and T2R imaging is a useful MR sequence for depicting the anatomy
      related to the fornix.

PMID- 11534692
TI  - Serial changes in signal intensities of the adjacent discs on T2-weighted
      sagittal images after surgical treatment of cervical spondylosis: anterior
      interbody fusion versus expansive laminoplasty.
AB  - BACKGROUND: There have been many reports about newly developed degenerative
      changes in the adjacent segments after anterior interbody fusion. It is a
      controversial issue whether the adjacent-segment disease in patients treated by
      anterior interbody fusion is the result of progressive cervical spondylosis at
      the adjacent levels or is caused by the arthrodesis. The aim of this study is to
      clarify the difference in postoperative effect on the adjacent segments between
      anterior interbody fusion and expansive laminoplasty. METHOD: This study included
      14 patients who underwent pre- and postoperative MR images at 6 and 12 months.
      Seven patients underwent cervical interbody fusion and the other 7 patients
      underwent expansive laminoplasty. Disc degeneration was evaluated
      semiquantitatively by calculating the degenerative index (DI) that is a ratio of
      the intensity in the disc to that in the upper cervical cord. FINDINGS: In the
      anterior interbody fusion group, the adjacent disc intensities decreased within
      12 months (F = 20.42; P < 0.01). The pre-operative mean DI was 0.59 +/- 0.16. The
      post-operative mean DIs were 0.56 +/- 0.16 at 6 months and 0.47 +/- 0.16 at 12
      months. In the expansive laminoplasty group, the signal intensities of both the
      adjacent discs and the discs within the range of laminoplasty had no serial
      changes during the same period (F = 2.67; P = 0.09 and F = 0.15; P = 0.87
      respectively). INTERPRETATION: Anterior interbody fusion had a significant
      influence on the adjacent discs even as soon as 12 months after surgery, but
      laminoplasty had no influence on them during the same period.

PMID- 11534693
TI  - Computed tomography of the brain in predicting outcome of traumatic intracranial
      haemorrhage in Malaysian patients.
AB  - Head injury is a significant economic, social and medical problem all over the
      world. Road accidents are the most frequent cause of head injury in Malaysia with
      highest risk in the young (15 to 24 years old). The associated outcomes include
      good recovery, possibility of death for the severely injured, which may cause
      disruption of the lives of their family members. It is important to predict the
      outcome as it will provide sound information to assist clinicians in Malaysia in
      providing prognostic information to patients and their families, to assess the
      effectiveness of different modes of treatment in promoting recovery and to
      document the significance of head injury as a public health problem. RESULTS: A
      total of 103 cases with intracranial haemorrhage i.e. intracerebral haemorrhage,
      extradural haemorrhage, subdural haemorrhage, intraventricular haemorrhage,
      haemorrhagic contusion and subarachnoid haemorrhage, following motor vehicle
      accidents was undertaken to study factors contributing to either good or poor
      outcome according to the Glasgow Outcome Scale. Patients below 12 years of age
      were excluded. The end point of the study was taken at 24 months post injury. The
      selected variables were incorporated into models generated by logistic regression
      techniques of multivariate analysis to see the significant predictors of outcome
      as well as the correlation between the CT findings with GCS. CONCLUSION:
      Significant predictors of outcome were GCS on arrival in the accident emergency
      department, pupillary reflex and the CT scan findings. The CT predictors of
      outcome include ICH, EDH, IVH, present of SAH, site of ICH, volumes of EDH and
      SDH as well as midline shift.

PMID- 11534694
TI  - In vitro therapy with dobutamine, isoprenaline and sodium nitroprusside protects
      vascular smooth muscle metabolism from subarachnoid haemorrhage induced cerebral
      vasospasm.
AB  - BACKGROUND: The cerebrospinal fluid (CSF) from subarachnoid haemorrhage (SAH)
      patients with cerebral vasospasm stimulates vasoconstriction and oxygen
      consumption in the porcine carotid artery in vitro. Stimulation of oxygen
      consumption has been used as an in vitro model of vasospasm to assess the
      relative benefits of nimodipine, isoprenaline, dobutamine, and sodium
      nitroprusside (SNP). METHOD: Samples of human CSF were obtained from SAH patients
      and applied to de-endothelialised porcine carotid artery. Stimulation of oxygen
      consumption (as an in vitro marker for a stimulation of the vessels) was
      monitored and the effects of SNP, isoprenaline, dobutamine or nimodipine were
      measured. FINDINGS: The CSF from SAH patients with evidence of vasospasm
      stimulated oxygen consumption to 0.91 +/- 0.17 (microM O2/min/g dry wt, +/- SD p
      < or = 0.01) and CSF from SAH patients without vasospasm did not significantly
      stimulate oxygen consumption 0.27 +/- 0.02, with 0.23 +/- 0.03 (microM O2/min/g
      dry wt) being an unstimulated rate of respiration for the porcine carotid artery.
      SNP, isoprenaline or dobutamine significantly (p < or = 0.01) decreased the
      stimulation of oxygen consumption of the porcine carotid artery whereas
      nimodipine did not. In a cohort of 41 SAH patients who received nimodipine alone
      or nimodipine and dobutamine, the in hospital mortality rate of the patients who
      received only nimodipine was 42% as compared to an in hospital mortality rate of
      17% in the nimodipine plus dobutamine group P < or = 0.076). INTERPRETATION: The
      in vivo data on the 41 patients is not statistically significant, so further
      studies are required to determine if the differences are important. SNP,
      isoprenaline and dobutamine significantly decreased oxygen consumption of the
      porcine carotid arteries exposed to CSF from SAH patients who had vasospasm
      whereas nimodipine did not. Our in vitro results suggest that these compounds
      require further study in patients with SAH who are at risk for vasospasm because
      they may have a direct benefit for the vasospastic arteries.

PMID- 11534695
TI  - Intracranial adenoid cystic carcinoma of suprasellar region.
AB  - Adenoid cystic carcinoma (ACC) is a relatively common head and neck tumor which
      grows slowly but locally aggressive and prone to recurrence. ACC most commonly
      arises in the major and minor salivary glands. Some rare cases of intracranial
      ACC with an unknown primary site have been reported. The authors present the
      first case of primary intracranial ACC of the suprasellar region. A 34 year-old
      female presented with one month's duration of visual disturbance and
      galactorrhea. Magnetic resonance image (MRI) showed intra- and suprasellar mass
      mimicking a craniopharyngioma. There was no evidence of invasion from an
      extracranial site. The operative findings showed the mass existed under the
      arachnoid membrane and seemed to originate from the pituitary stalk. Pathological
      diagnosis was ACC. After the first operation, local recurrence and CSF
      dissemination to the lower clivus occurred within two months. Recurrence
      repeatedly treated by Gamma knife radiosurgery 10 times and 4 times by surgery
      during a 3 year follow-up period. But total removal of the tumor at the first
      operation along with radiosurgery may control the lesion and prevent further
      recurrence.

PMID- 11534696
TI  - Antiproliferative effect of octreotide in somatotroph pituitary adenomas:
      discussion from a single case report.
AB  - The case of a 20-year-old man presenting with a rapidly expanding pituitary
      somatotrophic adenoma with a tumour volume doubling time of 426 days is reported.
      Preoperative octreotide therapy induced a 45% tumour shrinkage and proliferating
      cells were absent at the time of tumoural resection. The correlation between
      clinical and proliferation markers data in this single case report affords an
      opportunity to discuss the antitumoral effect of octreotide on somatotrophic
      adenomas which may result from a suppression of cell proliferation.

PMID- 11534697
TI  - Osteomyelitis of the skull vault induced by self-inflicted dermatitis of the
      scalp.

PMID- 11534698
TI  - Cauda equina sarcoidosis. Brief report of a special case.

PMID- 11534699
TI  - A method for measuring vapor pressures of low-volatility organic aerosol
      compounds using a thermal desorption particle beam mass spectrometer.
AB  - A temperature-programmed thermal desorption method for measuring vapor pressures
      of low-volatility organic aerosol compounds has been developed. The technique
      employs a thermal desorption particle beam mass spectrometer we have recently
      developed for real-time composition analysis of organic aerosols. Particles are
      size selected using a differential mobility analyzer, sampled into a high-vacuum
      chamber as an aerodynamically focused beam, collected by impaction on a
      cryogenically cooled surface, slowly vaporized by resistive heating, and analyzed
      in a quadrupole mass spectrometer. A simple evaporation model developed from the
      kinetic theory of gases is used to calculate compound vapor pressures over the
      temperature range of evaporation. The data are fit to a Clausius-Clapeyron
      equation to obtain a relationship between vapor pressure and temperature and to
      determine the heat of vaporization. The technique has been evaluated using C13
      C18 monocarboxylic and C6-C8 dicarboxylic acids, which have vapor pressures at 25
      degrees C of approximately 10(-4) - 10(-6) Pa, but less volatile compounds can
      also be analyzed. The method is relatively simple and rapid and yields vapor
      pressures and heats of vaporization that are in good agreement with literature
      values. The technique will be used to generate a new database of vapor pressures
      for low-volatility atmospheric organic compounds.

PMID- 11534700
TI  - Direct microextraction and analysis of rough-type lipopolysaccharides by combined
      thin-layer chromatography and MALDI mass spectrometry.
AB  - A rapid method for the microscale extraction of lipopolysaccharides (endotoxins,
      LPSs) from rough-type Gram-negative bacteria was developed using thin-layer
      chromatography (TLC) combined with improved conditions for LPS analysis by mass
      spectrometry. TLC of intact bacteria on silica gel plates in an appropriate
      solvent selectively extracted and separated their LPS components. The bands of
      molecular species were scraped from the plates after nondestructive
      visualization, directly mixed with matrix, and analyzed by laser desorption time
      of-flight mass spectrometry. Lipids A and Re-type LPSs were analyzed after
      transfer to a membrane. Adding citric acid to the matrix gave greatly improved
      mass spectra. The system allows characterization of bacterial LPS at the
      microscale level and is equally well applicable to heterogeneous LPS and lipid A
      preparations (Escherichia coli lipid A and Bordetella lipopolysaccharides were
      used). The technique provides a rapid determination of the heterogeneity of
      unmodified preparations and the determination of the molecular weight of each
      separated component.

PMID- 11534701
TI  - Profiling of isovalertatin family aminooligosaccharides extracted from the
      culture of Streptomyces luteogriseus by using liquid chromatography/electrospray
      ionization mass spectrometry.
AB  - A rapid and novel procedure using the liquid chromatography coupled to an
      electrospray ionization ion trap mass spectrometry technique was applied for the
      profiling of isovalertatin-family aminooligosaccharides in the extract from the
      culture filtrate of Streptomyces luteogriseus. The aminooligosaccharides were
      separated on a C-8 reversed-phase column with an acetonitrile-alkaline water
      gradient. The desired homologues were detected using the multiple reaction
      monitoring mode, and the chemical structures were confirmed by analyzing the
      characteristic fragment ions in their collision-induced dissociation spectra.
      This facile procedure led to the identification of all the five known
      aminooligosaccharides, isovalertatins M03, M13, M23, D03, and D23, in addition to
      the characterization of at least 41 novel isovalertatins, the molecular weights
      of which ranged from 729 to 2,793. This kind of assay should be intended as a
      simple and convenient way for the high-throughput analysis of screening
      aminooligosaccharides and potentially other structural families of natural
      products.

PMID- 11534702
TI  - Continuous-flow, on-line monitoring of biospecific interactions using
      electrospray mass spectrometry.
AB  - A continuous-flow analytical screening system is presented using electrospray
      mass spectrometry to measure the interaction of biologically active compounds
      with soluble affinity proteins. The biochemical detection system is based on a
      solution-phase, homogeneous assay. In a first step, compounds to be screened
      (e.g., biotinylated compounds, concentration range 10-1,000 nmol/L) are injected
      into a continuous-flow reaction system and allowed to react with the affinity
      protein (e.g., streptavidin, concentration range 3-48 nmol/L). Subsequently, a
      reporter ligand (fluorescein-labeled biotin 96 nmol/L) is added to saturate the
      remaining free binding sites of the affinity protein and the concentration of
      unbound reporter ligand is measured using electrospray MS in the selectedion
      monitoring mode. The presence of active compounds in the sample results in an
      increase of the concentration of unbound reporter ligands. The feasibility of a
      homogeneous MS-based biochemical assay is demonstrated using streptavidin/biotin
      and anti-digoxigenin/digoxin as model systems. Compared to radioactive or
      fluorescence-based biochemical assays, the present assay format does not require
      the synthesis and purification of labels. Various analytical conditions were
      investigated to determine the ability of MS to measure the biochemical
      interactions. The availability of a single ligand that can be detected at 10-50
      nmol/L concentrations by electrospray MS is sufficient to set up the biochemical
      assay. For the biospecific interactions studies, detection limits of 10-100
      nmol/L were obtained.

PMID- 11534703
TI  - Experimental upgrades of membrane introduction mass spectrometry for water and
      air analysis.
AB  - Some improvements to the membrane introduction mass spectrometry (MIMS)
      technique, resulting in low-ppt detection limits for volatile organohalogen
      compounds (CX) in water (namely, chloroform, bromoform, bromodichloromethane,
      chlorodibromomethane, tetrachloroethylene, trichloroethylene, 1,1,1
      trichloroethane, and carbon tetrachloride) and low-microgram per cubic meter
      detection limits for benzene, toluene, ethylbenzene, and xylenes (BTEX) in
      gaseous samples, are shown. A static MIMS configuration was compared to a dynamic
      one, the former requiring longer time to obtain the analytical response. A
      cryotrapping preconcentration step is introduced and linearity of response,
      mixture effects, and detection limits are presented. The instrumental setup
      consists of a hollow fiber silicone membrane, a water or air container, a
      cryofocusing trap based on Tenax adsorbent, a Peltier cell, and a Varian ion trap
      benchtop mass spectrometer is described. This instrumental setup, which we named
      membrane extraction trap focusing mass spectrometry, allowed the detection of CX
      in water at a concentration as low as 8 ppt and of benzene in air at 0.1
      microg/m3. The whole assembly shows great potential for on-site routine
      monitoring of drinking water resources and urban and indoor air under current EU
      and Italian regulations.

PMID- 11534704
TI  - Determination of aniline derivatives in oils related to the toxic oil syndrome by
      atmospheric pressure ionization-tandem mass spectrometry.
AB  - In 1981, an unknown disease appeared in Spain, the Spanish Toxic Oil Syndrome.
      Nowadays and despite all efforts, the etiological agent is still unknown. Early
      studies showed a link between this illness and the consumption of denatured
      rapeseed oil fraudulently processed and marketed as edible oil. Two families of
      aniline derivatives present in these oils (fatty acid anilides and acylated
      phenyl amino propanediol derivatives or PAPs) were found to be good chemical
      markers of toxic oils. In this work, a new method has been developed to analyze
      these aniline derivatives in oil samples by HPLC-MS and HPLC-MS/MS with an API
      source. For their quantification, three different internal standards were used,
      one for anilides and two for PAPs. Quantification limits were 8 ppm for anilides
      and 0.2 ppm for PAPs. Anilides and PAPs were found in marker-positive samples at
      levels up to 50,000 and 330 ppm, respectively. The relative abundance of the
      different fatty acid anilides and PAPs correlates with the fatty acid composition
      of the oils. More than 2,600 different samples were analyzed by this method in
      the most exhaustive screening of suspected toxic oils carried out to date.

PMID- 11534705
TI  - Capillary electrophoretic application of 1-alkyl-3-methylimidazolium-based ionic
      liquids.
AB  - Ionic substances with melting points at or close to room temperature are referred
      to as ionic liquids. Interest in ionic liquids for their potential in different
      chemical processes is increasing, because they are environmentally benign and are
      good solvents for a wide range of both organic and inorganic materials. In this
      study, a capillary electrophoretic method for resolving phenolic compounds found
      in grape seed extracts is reported. The method, in which 1-alkyl-3
      methylimidazolium-based ionic liquids are used as the running electrolytes, is
      simple and reproducible. The separation mechanism seems to involve association
      between the imidazolium cations and the polyphenols. The role of the alkyl
      substituents on the imidazolium cations was investigated and will be discussed.

PMID- 11534706
TI  - Photomodification of polymer microchannels induced by static and dynamic excimer
      ablation: effect on the electroosmotic flow.
AB  - This paper presents a study of polymer surfaces modified by laser ablation using
      poly(ethylene terephthalate) (PET) as a model system. The surface properties
      induced by static and dynamic ablation with the 193-nm pulsed radiation of an ArF
      excimer laser (4 x 10(7) W/cm2) in air have been successfully used to control the
      electroosmotic flow (EOF) in photoablated PET microchannels. Through the creation
      of well-defined static ablation patterns onto the walls of a trapezoidal channel,
      it was found that the resulting reduction in the EOF could be controlled. For
      example, a reduction of 25% in the EOF was observed in 42-microm-deep
      microchannels when using a static ablation pattern treating 50% of the total wall
      surface area. A numerical study describing the fluidic behavior induced by a
      static pattern is also presented. Moreover, X-ray photoelectron spectroscopy has
      been used to point out surface changes between static and dynamic ablation,
      thereby demonstrating an ability to create new functionalities in microchannels
      by laser treatment.

PMID- 11534707
TI  - Dielectric friction in capillary electrophoresis: mobility of organic anions in
      mixed methanol-water media.
AB  - The mobilities of a series of organic carboxylates and sulfonates, ranging in
      charge from -1 to -4, were investigated by capillary electrophoresis using
      buffers containing 0 to 75% (v/v) methanol. Effective mobilities were measured at
      a series of ionic strengths, and were extrapolated to zero ionic strength using
      Pitts' equation to yield absolute mobilities. Generally, higher-charged ions were
      more strongly influenced by ionic strength, as predicted by the Pitts' equation.
      Some differences in the ionic strength effects for anions of like charge were
      observed and were consistent with the relaxation effect. The absolute mobilities
      of anions were altered by the addition of methanol to the buffer. Analytes with
      higher charge-to-size ratios were slowed to a greater extent than were ions with
      lower charge-to-size. As a result, dramatic changes in relative mobility were
      observed, such as a reversal in migration order between anions of -1 and -4
      charge at 75% methanol and 20 mM ionic strength. The mobility changes caused by
      the addition of methanol are attributed to dielectric friction. Mobilities in the
      methanol-water solutions were found to depend on analyte charge-to-size and
      solvent dielectric relaxation time (tau) and were inversely dependent upon
      solvent dielectric constant (epsilon), as predicted by the Hubbard-Onsager
      mobility model.

PMID- 11534708
TI  - Protein analysis by capillary zone electrophoresis utilizing a trifunctional
      diamine for silica coating.
AB  - A novel method is here reported for the analysis of mixture of proteins with pI
      ranging from pH 3-9.5 in an ample pH interval (pH 2.5-9.0) without adsorption
      onto the naked silica wall. It consists of treating the capillary surface at
      alkaline pH, typically 9.0, with small amounts (2-4 mM) of a quaternarized
      piperazine derivative: (N-methyl-N-omega-iodobutyl)-N'-methylpiperazine (Q-PzI).
      It appears that this compound is able to dock onto the wall via trifunctional
      links: a salt bridge via the quaternary nitrogen, a hydrogen bond via the
      tertiary nitrogen, and finally, a covalent link via the terminal iodine in the
      butyl chain and a neighboring ionized silanol. This last reaction seems to be
      completed in a few minutes of incubation of the capillary at room temperature.
      Because the compound is permanently affixed to the wall, its presence is not
      needed during protein/peptide separations. By properly dosing the level of Q-PzI
      in the preconditioning step, it is possible to strongly reduce the
      electroendoosmotic flow (EOF), zero it, or reverse it. Unlike dynamic coatings
      with oligoamines, which are most effective only at acidic pH values and are
      required as additives during separations, Q-PzI is effective in an ample pH
      interval (pH 2.5-9.0) and is not needed during the CZE analysis. A broad pI (pH 3
      10) protein mix can be separated according to protein mobility in free phase,
      suggesting a strong modulating capacity of the functionalized wall. The same
      separation is not obtained in capillaries permanently coated with neutral,
      hydrophilic polymers (such as polyacrylamide), even if the quality of a single
      protein/peptide profile in Q-PzI-conditioned capillaries is equivalent to those
      obtained in capillaries permanently coated. Although there is strong indirect
      evidence of the ability of Q-PzI to alkylate the silica wall, to which it is then
      irreversibly bound, such an alkylation event does not occur with proteins on
      potentially reacting sites, such as the free -SH of Cys or the -OH group of Tyr,
      as demonstrated by incubating them overnight in a large molar excess at strongly
      alkaline pH values and analyzing such proteins by MALDI-TOF mass spectrometry.

PMID- 11534709
TI  - Moleculary imprinted polymers with metalloporphyrin-based molecular recognition
      sites coassembled with methacrylic acid.
AB  - A diastereoselective molecularly imprinted polymer (MIP) for (-)-cinchonidine,
      PPM(CD), was prepared by the combined use of methacrylic acid and vinyl
      substituted zinc(II) porphyrin as functional monomers. Compared to MIPs using
      only methacrylic acid or zinc porphyrin as a functional monomer, PM(CD) and
      PP(CD), respectively, PPM(CD) showed higher binding ability for (-)-cinchonidine
      in chromatographic tests using the MIP-packed columns. Scatchard analysis gave a
      higher association constant of PPM(CD) for (-)-cinchonidine (1.14 x 10(7) M(-1))
      than those of PP(CD) (1.45 x 10(6) M(-1)) and PM(CD) (6.78 x 10(6) M(-1)). The
      affinity distribution of binding sites estimated by affinity spectrum analysis
      showed a higher percentage of high-affinity sites and a lower percentage of low
      affinity sites in PPM(CD). The MIPs containing a zinc(II) porphyrin in the
      binding sites, PPM(CD) and PP(CD), showed fluorescence quenching according to the
      binding of (-)-cinchonidine, and the quenching was significant in the low
      concentration range, suggesting that the high-affinity binding sites contain the
      porphyrin residue. The correlation of the relative fluorescence intensity against
      log of (-)-cinchonidine concentrations showed a linear relationship. These
      results revealed that the MIP having highly specific binding sites was assembled
      by the two functional monomers, vinyl-substituted zinc(II) porphyrin and
      methacrylic acid, and they cooperatively worked to yield the specific binding. In
      addition, the zinc(II) porphyrin-based MIPs appeared to act as fluorescence
      sensor selectively responded by binding events of the template molecule.

PMID- 11534710
TI  - Microcalorimetric studies on the interaction mechanism between proteins and
      hydrophobic solid surfaces in hydrophobic interaction chromatography: effects of
      salts, hydrophobicity of the sorbent, and structure of the protein.
AB  - This study examines the effects of different salts as well as the influence of
      the relative hydrophobicities of different sorbents on the adsorption processes
      of proteins in hydrophobic interaction chromatography (HIC). Comparative data
      acquired by the equilibrium binding analysis and by isothermal titration
      microcalorimetry (ITC) are presented. In particular, thermodynamic parameters,
      including the enthalpy changes, related to the interactions between several
      globular proteins and various Toyopearl 650 M sorbents under solvent conditions
      containing either 2.0 M ammonium sulfate or 2.0 M sodium sulfate at pH 7.0 and
      298.15 K have been evaluated in terms of the molecular properties of these
      systems. The results reveal that the dependence of the free energy change,
      deltaGads, for protein adsorption to HIC sorbents on the salt composition can be
      mainly attributed to the enthalpy changes associated with protein and sorbent
      dehydration and hydrophobic interactions. Differences in binding mechanisms
      between the n-butyl- and phenyl-HIC sorbents were evident. In the latter case,
      the participation of pi-pi hydrophobic interactions leads to significant
      differences in the associated enthalpy and entropy changes. Furthermore, an
      increase in the hydrophobicity of either the sorbent or the protein resulted in
      more negative values for the free energy change, which arose mostly from
      dehydration processes. Entropic effects favoring HIC adsorption increased with an
      increase in the exposed nonpolar surface area of the protein. Consequently, an
      increased contribution from the entropy change to the respective change in free
      energy occurs when HIC sorbents or proteins of higher hydrophobicity are
      employed, with these larger entropy changes consistent with a change in the
      interaction mechanism from a binding event dominated by adsorption to a
      partitioning-like process. Data extracted from the ITC measurements also provided
      insight into the interaction mechanisms that occur between proteins and
      hydrophobic solid surfaces, yielding information that can be applied to the HIC
      purification of proteins according to the concept of critical hydrophobicity of
      the system and its thermodynamic consequences.

PMID- 11534711
TI  - Liquid chromatography at the critical condition for polyisoprene using a single
      solvent.
AB  - Liquid chromatography at the chromatographic critical condition has drawn much
      attention as an attractive characterization method of block copolymers since it
      has been proposed that a part of a polymer chain becomes "chromatographically
      invisible" at this condition, which would permit the characterization of
      individual blocks. A critical condition for a polymer species has been commonly
      established by use of mixed-solvent systems. It is not easy, however, to
      reproduce the critical condition since the retention of polymers depends very
      sensitively on the solvent composition and purity. Furthermore, the preferential
      sorption of a component in a mixed solvent may cause an additional problem.
      Therefore, the use of a single solvent is highly desirable to improve the
      reproducibility as well as the repeatability. In this study, a single-solvent
      critical condition for polyisoprene was established with 1,4-dioxane and C18
      bonded silica as the mobile and stationary phases, respectively. At this
      condition, the "chromatographic invisibility" of polystyrene-polyisoprene diblock
      copolymers was critically examined and it was found that a rigorous
      chromatographic invisibility was not achieved and the retention of the block
      copolymers was affected by the length of the blocks under the critical condition.
      Some other chromatographic applications using the single-solvent system are also
      reported.

PMID- 11534712
TI  - Determination of steroid estrogens in wastewater by immunoaffinity extraction
      coupled with HPLC-electrospray-MS.
AB  - A new method, based on immunoaffinity extraction coupled with liquid
      chromatography/electrospray mass spectrometry (LC/ESI-MS) is described for the
      determination of the steroid estrogens beta-estradiol (E2), estrone (E1), and
      alpha-ethynylestradiol (E2) in wastewater. The use of highly selective
      immunosorbents in sample preparation prior to analysis allows the removal of
      interfering sample matrix compounds present in the wastewater extracts that would
      otherwise cause severe ionization suppression of the estrogens during the
      electrospray process. In addition, immunoextraction removes much of the isobaric
      noise from the selected ion monitoring chromatograms, increasing the signal-to
      noise ratios for analytes, and contributing to the low detection limits (0.18 and
      0.07 ng/L for E2 and E1, respectively) achieved by the current method. The method
      was applied to analysis of estrogens in two wastewater effluents. Recoveries of
      E2 and E1 were excellent (>90%), while the nonimmunogen (but structurally
      related) analyte EE2 was not retained (recovery <2%) from effluent extracts by
      the immunosorbent. This illustrates the extreme selectivity of the
      immunoextraction purification step. Precision of the method was high, with
      relative standard deviations below 5%. Concentrations of E2 in wastewater varied
      from 0.77 to 6.4 ng/L, while concentrations of E1 were greater (1.6-18 ng/L).

PMID- 11534713
TI  - Separation of selected anticancer drugs using superheated water as the mobile
      phase.
AB  - Six anticancer drugs have been eluted on a polystyrene-divinylbenzene (PS-DVB)
      column with buffered superheated water as the mobile phase. The temperature range
      studied was from ambient temperature up to 160 degrees C, and the pH of the water
      was adjusted to 11.5 and 3.5 with phosphate buffer. It was possible to separate
      the substances 5-fluorouracil (5-FU), methotrexate (MTX), 7-hydroxymethotrexate
      (7-OH-MTX), and etoposide (VP-16) in one chromatographic run. The separation of
      these substances was optimized when adjusting the pH from 11.5 to 3.5, resulting
      in a total elution time of less than 13 min. Furthermore, retention factors of
      all of the investigated substances were measured at different temperatures and pH
      values.

PMID- 11534714
TI  - Complexes between monoclonal antibodies and receptor fragments with a common cold
      virus: determination of stoichiometry by capillary electrophoresis.
AB  - Complex formation between monoclonal antibodies or soluble receptor fragments and
      a human rhinovirus is quantified by relating the concentration of the antibody or
      receptor under equilibrium conditions to the initial concentration of the virus.
      Within a given concentration range of the reactants, the shape of the resulting
      curve depends only on the value of the dissociation constant of the particular
      system studied. Using antibodies and receptor fragments, cases for high, low, and
      intermediate affinity were investigated. For high-affinity systems, the curve
      approximates a decaying straight line and the binding stoichiometry can be
      accurately determined from the intercept with the x-axis. For the case of
      intermediate affinity, the curve can be linearized at low virus concentrations
      with the receptors present in large excess. Extrapolation of this line allows
      derivation of the binding stoichiometry from the intercept with the x-axis,
      although with less accuracy. For intermediate affinities, an estimate of the
      dissociation constant can be obtained from fitting the curve to the data points
      measured. Finally, in the case of low affinity none of the binding parameters can
      be quantified, although a rough estimate of the lower limit of the dissociation
      constant is possible. The method was applied for two different monoclonal
      antibodies, a Fab fragment and a receptor fragment, binding to human rhinovirus
      serotype 2. Thirty copies of the monoclonal antibody 8F5 were found to bind to
      the virion, which is in agreement with data from electron cryomicroscopy. The
      complex between monovalent human very-low-density lipoprotein receptor
      encompassing repeats 2 and 3 and human rhinovirus serotype 2 showed 60 receptor
      molecules bound per virion.

PMID- 11534715
TI  - Resonance Rayleigh scattering study of the interaction of heparin with some basic
      diphenyl naphthylmethane dyes.
AB  - In a near-neutral medium, a combination of heparin with some basic diphenyl
      naphthylmethane dyes such as victoria blue 4R (VB4R), victoria blue B (VBB), or
      night blue (NB) can result in a significant enhancement of resonance. Rayleigh
      scattering (RRS) and their maximum scattering wavelengths lambdamax appear at
      523, 534, and 540 nm for VB4R, VBB, and NB, respectively. The characteristics of
      RRS spectra of the heparin-dye complexes, the influencing factors, and the
      optimum conditions of these reactions have been investigated. The RRS intensity
      is directly proportional to the concentration of heparin in the range of
      approximately 0 to 0.4 microg/mL for all systems. The methods exhibit high
      sensitivities, and the detection limits for heparin are 3.35 ng/mL for the VB4R
      system, 6.62 ng/ mL for the VBB system, and 6.29 ng/mL for the NB system. Because
      the VB4R system is the most sensitive, it was taken as an example to study the
      selectivity of the method. A new method for the determination of trace amounts of
      heparin based on RRS technique has been developed. Moreover, the enhancement
      reasons of RRS and the relationship between RRS spectral characteristics of the
      heparin-dye complex and its absorption spectra have been primarily discussed.

PMID- 11534716
TI  - Determination of water concentration in brain tissue by Raman spectroscopy.
AB  - Brain edema is one of the most common morbidity factors in patients with
      intracranial neoplasms and cerebrovascular pathology. Monitoring of intracranial
      pressure gives only an indirect and global measure of brain swelling. We have
      made an assessment of the applicability of Raman spectroscopy as an alternative
      method for assessing brain edema, which measures the water concentration in the
      tissue directly. Partial least-squares models were developed on the basis of
      Raman spectra measured in the 2600-3800-cm(-1) region, which predict the water
      fraction of brain tissue in the 0.75-0.95 range, with an accuracy better than
      0.01.

PMID- 11534717
TI  - Photopolymerized sol-gel monoliths for capillary electrochromatography.
AB  - A solution of methacryloxypropyltrimethoxysilane in the presence of an acid
      catalyst, water, toluene, and a photoinitiator was irradiated at 365 nm for 5 min
      in a 75-microm i.d. capillary to prepare a porous monolithic sol-gel column by a
      one-step, in situ, process. The photopolymerized sol-gel (PSG) column shows
      reversed-phase behavior. Using this column, a variety of low-molecular-weight
      neutral compounds, including polycyclic aromatic hydrocarbons, alkyl benzenes,
      alkyl phenyl ketones, and steroids are separated from mixtures. Various different
      operational parameters, such as buffer composition, field strength, and column
      temperature, were varied to assess their influence on column performance. Use of
      PSG as a stationary phase for a pressure-driven separation is also demonstrated.

PMID- 11534718
TI  - Comparison of three coupled gas chromatographic detectors (MS, MIP-AES, ICP
      TOFMS) for organolead speciation analysis.
AB  - An automatic unit for the screening of rainwater is used for the determination of
      organolead compounds using different detectors coupled to a gas chromatograph. A
      systematic overview is given of the advantages and disadvantages of several
      detectors (electron ionization mass spectrometry, EI-MS; microwave induced plasma
      atomic emission spectrometry, MIP-AES; and inductively coupled plasma time-of
      flight mass spectrometry, ICP-TOFMS, for the speciation of organolead compounds
      on the basis of sensitivity, selectivity and reliability. C60 fullerene and RP
      C18 were used as sorbent materials for these compounds. The primary assets of the
      fullerene sorbent, as compared to C18 sorbent, are high sensitivity and
      selectivity resulting from efficient adsorption due to large surface area and
      interstitial volume. Among the detection systems, GC/ ICP-TOFMS is the most
      sensitive, with absolute detection limits of approximately 15 fg of organolead
      compounds (as lead) using 5-mL sample volumes. Except for diethyllead, similar
      sensitivities were obtained by MIP-AES. GC/MS is intrinsically the most specific
      option, because the species are detected directly from molecular information. The
      precision is similar for all detectors. The screening of rainwater from different
      locations showed that samples collected in countries in which leaded gasolines
      are now banned contain organolead species at concentrations below 2 pg/ mL,
      levels that can be detected only for sample volumes of 25 mL and using MIP-AES or
      ICP-TOFMS as detectors, their determination being impossible by GC/MS.

PMID- 11534719
TI  - Direct and quantitative detection of bacteriophage by "hearing" surface
      detachment using a quartz crystal microbalance.
AB  - We show that it is possible to detect specifically adsorbed bacteriophage
      directly by breaking the interactions between proteins displayed on the phage
      coat and ligands immobilized on the surface of a quartz crystal microbalance
      (QCM). This is achieved through increasing the amplitude of oscillation of the
      QCM surface and sensitively detecting the acoustic emission produced when the
      bacteriophage detaches from the surface. There is no interference from
      nonspecifically adsorbed phage. The detection is quantitative over at least 5
      orders of magnitude and is sensitive enough to detect as few as 20 phage. The
      method has potential as a sensitive and low-cost method for virus detection.

PMID- 11534720
TI  - Development of a fully integrated analysis system for ions based on ion-selective
      optodes and centrifugal microfluidics.
AB  - A fully integrated, miniaturized analysis system for ions based on a centrifugal
      microfluidics platform and ion-selective optode membranes is described. The
      microfluidic architecture is composed of channels, five solution reservoirs, a
      measuring chamber, and a waste reservoir manufactured onto a disk-shaped
      substrate of poly(methyl methacrylate). Ion-selective optode membranes, composed
      of plasticized poly(vinyl chloride) impregnated with an ionophore, a proton
      chromoionophore, and a lipophilic anionic additive, were cast, with a spin-on
      device, onto a support layer and then immobilized on the disk. Fluid propulsion
      is achieved by the centrifugal force that results from spinning the disk, while a
      system of valves is built onto the disk to control flow. These valves operate
      based on fluid properties and fluid/substrate interactions and are controlled by
      the angular frequency of rotation. With this system, we have been able to deliver
      calibrant solutions, washing buffers, or "test" solutions to the measuring
      chamber where the optode membrane is located. An analysis system based on a
      potassium-selective optode has been characterized. Results indicate that optodes
      immobilized on the platform demonstrate theoretical responses in an absorbance
      mode of measurement. Samples of unknown concentration can be quantified to within
      3% error by fitting the response function for a given optode membrane using an
      acid (for measuring the signal for a fully protonated chromoionophore), a base
      (for fully deprotonated chromoionophore), and two standard solutions. Further,
      the ability to measure ion concentrations by employing one standard solution in
      conjunction with acid and base and with two standards alone were studied to
      delineate whether the current architecture could be simplified. Finally, the
      efficacy of incorporating washing steps into the calibration protocol was
      investigated.

PMID- 11534722
TI  - Chemical modification of carbonaceous stationary phases by the reduction of
      diazonium salts.
AB  - This paper describes a new strategy for the creation of chemically modified
      carbonaceous stationary phases. The strategy exploits the electroreduction of
      arenediazonium salts as a means for functionalizing the surface of glassy carbon
      (GC) and porous graphitic carbon (PGC) stationary phases. The one-electron
      reduction of these salts forms an arene radical which then couples via a carbon
      carbon linkage to the carbon framework at the surface of the stationary phase.
      Two arenediazonium-based modifiers were used in evaluating the potential utility
      of this strategy: 4-nitrobenzenediazonium tetrafluoroborate for the GC and PGC
      phases and 4-hexylbenzenediazonium tetrafluoroborate for only the PGC phases.
      Modifications were carried out by packing the phases into a column used for
      electrochemically modulated liquid chromatography. The effectiveness of the
      modifications was assessed by X-ray photoelectron spectroscopy and by comparing
      the liquid separation of a series of mixtures before and after coating
      deposition. For the nitrobenzyl-modified GC phase, the test mixture contained
      both anisole and fluoranthene. The performance of the nitrobenzyl- and
      hexylbenzyl-modified PGC stationary phases was characterized by the separations
      of substituted phenols (i.e., nitrophenol and resorcinol) and a few important
      pharmaceutical agents (i.e., hexobarbital, oxazepam, and nitrazepam). The
      potential utility of this modification procedure to form stationary phases that
      are stable upon extended exposure to aggressive mobile phases is discussed and
      briefly examined.

PMID- 11534721
TI  - Dynamic secondary ion mass spectrometry analysis of boron from boron neutron
      capture therapy drugs in co-cultures: single-cell imaging of two different cell
      types within the same ion microscopy field of imaging.
AB  - A co-culture, cryogenic SIMS methodology is presented for the quantitative
      analysis of cell type-dependent accumulation of boron delivered by BPA-F and BSH,
      two clinically approved drugs used in boron neutron capture therapy of cancer.
      T98G human glioblastoma cells were co-cultured with morphologically different
      normal LLC-PK1 epithelial cells or GM3348 human skin fibroblasts. Our freeze
      fracture method of cryogenic sample preparation successfully fractured the
      different cell types grown together in co-cultures. Quantitative observations
      revealed an active uptake of boron from BPA-F in both T98G and LLC-PK1 cells but
      did not show cell type-dependent differences. Accumulation of BSH in all three
      cell types examined also did not reveal any cell type-dependent differences in co
      cultures. As this method relies on the analysis, within the same field of SIMS
      imaging, of two different cell types that have been maintained under identical
      conditions of growth, drug exposure, sample preparation, and instrumental
      analysis, it provides the most effective approach for comparing cell type
      specific differences in boron concentrations. The most effective applications of
      this method will be realized in testing the selectivity of experimental boronated
      compounds designed to specifically target tumor cells.

PMID- 11534723
TI  - Electrogenerated chemiluminescence. 67. Dependence of light emission of the
      tris(2,2')bipyridylruthenium(II)/tripropylamine system on electrode surface
      hydrophobicity.
AB  - We describe the effect of electrode surface hydrophobicity on the electrochemical
      behavior and electrogenerated chemiluminescence (ECL) of Ru(bpy)3(2+) (bpy = 2,2'
      bipyridyl)/tripropylamine (TPrA) system. Gold and platinum electrodes were
      modified with different thiol monolayers. The hydrophobicity of the electrode
      surfaces changed with different terminal groups of the thiol molecules. The
      oxidation rate of TPrA was found to be much larger at the modified electrode with
      a more hydrophobic surface. The adsorption of neutral TPrA species on this kind
      of surface was assumed to contribute to the faster anodic kinetics. Due to the
      rapid generation of the highly reducing radical, TPrA., ECL intensity increased
      significantly at more hydrophobic electrodes. This electrode surface effect in
      the ECL analytical system allows one to improve the detection sensitivity at low
      concentrations of Ru(bpy)3(2+). The surfactant effect on the ECL process was also
      examined and discussed based on the change of electrode hydrophobicity by the
      adsorption of surfactant species.

PMID- 11534724
TI  - Stationary-state oxidized platinum microsensor for selective and on-line
      monitoring of nitric oxide in biological preparations.
AB  - Despite the multifaceted biomedical significance of NO, little progress has been
      achieved so far in the quantitative understanding of the signal transduction
      mechanisms where NO is involved. To help progress in this area, we propose a
      simple electrochemical NO sensor here, consisting of a glass sealed platinum
      microdisk electrode coated with cellulose acetate to reduce both surface fouling
      by proteins and response to potential interferences. A differential amperometry
      protocol is optimized to improve selectivity and provide a stationary oxidation
      state of the platinum surface, which prevents loss in sensitivity during long
      term use. We found the oxidation of NO by O2 second order in [NO] with a rate
      constant of (8.0 +/- 0.4) x 10(6) M(-2) s(-1), in good agreement with literature
      data obtained by other than electrochemical methods. The release rates of NO
      detected in cultures of activated macrophages were on the order of 20 pmol/
      (10(6)cells s) and correlated well with the nitrite content determined by the
      spectrophotometric Griess assay.

PMID- 11534725
TI  - Self-assembled monolayer of a redox-active calix[4]arene: voltammetric
      recognition of the Ba2+ ion in aqueous media.
AB  - The Redox-active monolayer of a novel calix[4]arene recognizing redox-inactive
      ionic species by voltammetry is reported. Calix[4]arene-disulfide-diquinone,
      which is not only redox-active but is also a highly selective ionophore for the
      Ba2+ ion, spontaneously forms a stable and dense monolayer film on gold. The
      redox-active calixarene monolayer selectively recognizes Ba2+ ion in aqueous
      media, and the voltammetric signals are proportional to the ionic concentration.
      A new voltammetric peak can be detected by square-wave voltammetry upon adding a
      dilute solution containing Ba2+ ion having a concentration as low as 1.0 x 10(-6)
      M. The Langmuir plot (1/ip vs 1/[Ba2+]) shows a linear slope in the range from
      1.0 x 10(-6) M to 1.0 x 10(-4) M. This modified electrode does not show any
      significant interference from alkali and alkaline earth metal ions except for
      Sr2+ and Ca2+. Only 100- and 500-fold concentrations of Sr2+ and Ca2+ ions,
      respectively, can lead to voltammetric responses comparable to that of Ba2+.

PMID- 11534726
TI  - Magnetohydrodynamic electrochemistry in the field of Nd-Fe-B magnets. Theory,
      experiment, and application in self-powered flow delivery systems.
AB  - Nd-Fe-B permanent magnets are easily available, powerful, and inexpensive and
      generate strong quantifiable convective effects during electrolysis, similar to
      those obtained with rotating electrodes or large electromagnets. The magnetic
      field of Nd-Fe-B magnets has been simulated numerically and mapped. Its most
      characteristic difference from the field of most commercial electromagnets is the
      presence of magnetic field gradients, which introduce additional body forces in
      the electrolytic solution and create new modes of mass transfer due to the
      attraction of electrogenerated radicals into areas of stronger field. The effect
      of those new forces on the radial distribution of the flow profile in the
      vicinity of the electrode has been monitored with generation-collection
      experiments and optical photography. The emerging utility of Nd-Fe-B magnets in
      systems of chemical interest is demonstrated with flow control and delivery
      devices, based on galvanic cells configured as self-powered magnetohydrodynamic
      pumps.

PMID- 11534727
TI  - Microscopic imaging with electrogenerated chemiluminescence.
AB  - The use of electrogenerated chemiluminescence (ECL) at microelectrodes as a light
      source for scanning optical microscopy is demonstrated. Cone-shaped
      microelectrodes were constructed by flame etching carbon fibers to a fine point.
      ECL generated in solution at such electrodes was forced to the apex of the
      conducting surface by using high-frequency (20-kHz) potential pulses and high
      concentrations of ECL reagents in the solution. ECL arose from the reaction of
      9,10-diphenylanthracene radical cation with the radical anion of benzonitrile,
      the solvent. The electrode/light source was raster-scanned a finite distance
      above the sample surface, and images were generated with standard scanning probe
      software by collecting the transmitted light with a microscope objective. These
      images compared favorably to optical images of the same sample. A resolution of
      approximately 600 nm was achieved with this arrangement even though a feedback
      loop was not employed to control the tip distance from the sample. The source was
      sufficiently bright (1.82 pW) that well-defined transmittance spectra could be
      obtained at individual locations on the sample.

PMID- 11534728
TI  - Use of dyes to investigate migration of the chiral selector in CFFE and the
      impact on the chiral separations.
AB  - Continuous free flow electrophoresis was investigated as a tool for the
      preparative chiral separation of piperoxan enantiomers using sulfated beta
      cyclodextrin (sbeta-CD) as the chiral additive. Bulk migration of sbeta-CD was
      confirmed using LC-MS analysis of the individual fractions collected and
      visualized with the addition of crystal violet to the separation buffer. In the
      absence of sbeta-CD, the crystal violet-containing buffer was reddish/purple and
      the crystal violet was deflected cathodically in the chamber. In the presence of
      sbeta-CD, the crystal violet-containing buffer was blue and was deflected
      anodically. However, formation of accumulation and depletion zones was apparent
      in both cases. The addition of sbeta-CD to the cathodic wash solution allowed for
      almost complete resolution of the piperoxan enantiomers with a processing rate of
      0.45 mg/ h.

PMID- 11534729
TI  - Surface coverages of bonded-phase ligands on silica: a computational study.
AB  - A computational study of the packing of various bonded-phase ligands bound to
      chromatographic silica is presented. This is done with the intention of examing
      the type of surface structures that are typically found in real chromatographic
      systems. Utilizing the surface structure of the (111) face of the beta
      cristobalite crystal, it is shown that the maximum surface coverages of
      dimethyloctylsilane, dimethyloctadecylsilane, triisopropylsilane,
      diisopropyloctylsilane, and diisopropyloctadecylsilane can be calculated that are
      in good agreement with experiment. The maximum surface coverages are also
      calculated for the (100) face of the beta-cristobalite crystal and for a set of
      random silica surfaces. The coverages for the latter two surfaces types are found
      to be significantly lower than the experimental values for chromatographic silica
      surfaces. These results further suggest that chromatographic silica surfaces may
      resemble crystalline surface sites similar to the (111) face of beta
      cristobalite, as has been previously suggested in the literature. Hence, these
      structures can be reliably utilized in molecular simulations of bonded-phase
      chromatography where the atomic-level detail of the silica surface has been
      previously lacking.

PMID- 11534730
TI  - A general strategy for epitope mapping by direct MALDI-TOF mass spectrometry
      using secondary antibodies and cross-linking.
AB  - The combination of limited proteolysis and MALDI-TOF mass spectrometry has become
      an important tool for the determination of epitopes but works best with highly
      purified antibodies. Here we report the use of capture antibodies to reduce the
      need for purification of the antibody in the mass spectrometric determination of
      the epitope. In this new method, a secondary Fc-specific antibody, covalently
      bound to Sepharose beads, is used to capture the primary antibody (the antibody
      of interest). After capture, the two antibodies are cross-linked. The antigen is
      then bound to the immobilized antibodies and subjected to proteolysis using
      several successive proteinases. In this study, this strategy is demonstrated with
      a crude mouse anti-ACTH IgG solution and adrenocorticotropin (ACTH). Comparing
      this strategy with previous methods where the antibody is bound directly to
      activated beads, the new method (1) results in a higher binding capacity of the
      bound antibody to ACTH, (2) does not require purification of the antibody of
      interest, and (3) dramatically reduces the chemical background in the MALDI mass
      spectra.

PMID- 11534731
TI  - Validation of methylmercury determinations in aquatic systems by alkyl
      derivatization methods for GC analysis using ICP-IDMS.
AB  - Isotope dilution mass spectrometry (IDMS), using an inductively coupled plasma
      quadrupole mass spectrometer (ICPMS) and a species-specific methylmercury spike
      was applied to validate the commonly used GC method for methylmercury (MeHg+)
      determination, which is based on the formation of volatile methylethylmercury by
      derivatizationwith NaBEt4. The spike compound, Me201Hg+, was synthesized by
      reaction of 201Hg-enriched mercury chloride with methylcobalamin. By analyzing
      different environmental aquatic samples, it was found that in most cases,
      transformation of MeHg+ into elemental mercury (Hg0) took place. From
      investigations of synthetic solutions, it could be followed that halide ions are
      responsible for this transformation process. Chloride and bromide converted MeHg+
      into Hg0, whereas iodide caused transformation into Hg2+ and Hg0. It could also
      be shown that transformation of MeHg+ took place only during the derivatization
      step. In contrast to ethylation, propylation by NaBPr4 did not cause any
      transformation; however, accurate results of MeHg+ determinations could be
      obtained by propylation as well as by ethylation when GC/ ICP-IDMS was applied.
      This work demonstrates the great power of isotopically labeled element compounds
      for the validation of element speciation methods and for species-specific IDMS
      analyses.

PMID- 11534732
TI  - Basicity of the amino groups of the aminoglycoside amikacin using capillary
      electrophoresis and coupled CE-MS-MS techniques.
AB  - This paper describes the use of capillary electrophoresis (CE), and coupled CE
      and mass spectrometric techniques, to measure the values of the pKa of the amino
      groups of the aminoglycoside antibiotic amikacin and of its acetylated
      derivatives. These values of pKa (8.4, 6.7, 9.7, 8.4) were determined by
      measuring the electrophoretic mobilities of the molecules as a function of pH;
      they are within 0.7 unit of certain values reported in the literature (by 13C and
      15N NMR spectroscopies) but resolved ambiguities left by these earlier studies.
      The range of values of pKa of amino groups also indicates the complex dependence
      of the acidity of a functional group (and thus the extent of ionization at a
      specified value of pH) on the molecular environment of that group.

PMID- 11534733
TI  - Photothermal temperature control of a chemical reaction on a microchip using an
      infrared diode laser.
AB  - We have demonstrated that a miniaturized device with IR laser heating of the
      solvent, based on a photothermal effect, is capable of fast and localized control
      of an enzymatic reaction on a microchip under flow conditions. Using noncontact
      spectroscopic temperature-sensing techniques, we measured temperature dynamics
      and spatial distribution and compared the measurements with results of numerical
      simulation analysis. The device was operated at ultrafast heating and cooling
      rates of 67 and 53 degrees C/s, respectively, which is 30 times faster than
      conventional systems and 3-6 times faster than electrothermal miniaturized
      thermocyclers. The IR laser-mediated heater is characterized by a significantly
      reduced heated volume of only 5 nL, compared to existing chip-based systems with
      electrothermal heating. Direct heating of a sample with extremely small heat
      capacity led us to a fast heating rate, and efficient heat removal through heat
      transfer to the glass substrate resulted in a fast cooling rate. Reproducible
      temperature levels with dwell times shorter than 0.5 s were achieved. The enzyme
      reaction on a chip was successfully controlled with 0.6-s time resolution, using
      periodic photothermal heating by IR laser. The IR diode laser is compact and thus
      suits well the miniaturized system design. Our work gives the basis for
      integration in a chip format of a variety of chemical processes that require fast
      temperature control.

PMID- 11534734
TI  - Electroosmotically induced hydraulic pumping with integrated electrodes on
      microfluidic devices.
AB  - Electroosmotic manipulation of fluids was demonstrated using thin metal
      electrodes integrated within microfluidic channels at the substrate and cover
      plate interface. Devices were fabricated by photolithographically patterning
      electrodes on glass cover plates that were then bonded to polymeric substrates
      into which the channels were cast. Polymeric substrates were used to provide a
      permeable membrane for the transport and removal of gaseous electrolysis products
      generated at the electrodes. Electroosmotic flow between interdigitated
      electrodes was demonstrated and provided electric field-free pumping of fluids in
      sections of the channel outside of the electrode pairs. The resultant pumping
      velocities were shown to be dependent on the applied voltage, not on the applied
      field strength, and independent of the length of the electroosmotically pumped
      region.

PMID- 11534735
TI  - Comparison of fat retainers in accelerated solvent extraction for the selective
      extraction of PCBs from fat-containing samples.
AB  - Five types of fat retainers were investigated for the lipid-free extraction of
      PCBs from fat-containing matrixes using accelerated solvent extraction: florisil,
      basic alumina, neutral alumina, acidic alumina, and sulfuric acid-impregnated
      silica. All of the fat retainers generated fat-free extracts when the fat/fat
      retainer ratio was 1:40. Sulfuric acid-impregnated silica and florisil were the
      only retainers that gave completely clear extracts, and the former was the only
      not to show any reaction when treated with sulfuric acid after the extraction.
      Using sulfuric acid-impregnated silica as fat retainer, on-line cleanup of fat
      containing matrixes was possible, as demonstrated for naturally contaminated fish
      meal as well as certified cod liver oil (CRM 349).

PMID- 11534736
TI  - Anodized aluminum wire as a solid-phase microextraction fiber.
AB  - The efficiency of anodized aluminum wire was investigated as a new fiber for
      solid-phase microextraction (SPME). Aluminum wires were anodized by direct
      current in a solution of sulfuric acid at room temperature and were conditioned
      at 300 degrees C for 30 min. These fibers were used for the extraction of some
      aliphatic alcohols, BTEX, and petroleum products from gaseous samples. The
      extracted analytes were transferred to a GC injector using an (inhouse-designed)
      SPME syringe that also allowed for an easy change of SPME fibers. The results
      obtained prove the ability of anodized aluminum wire as a new fiber for sampling
      of organic compounds from gaseous samples. This behavior is due most probably to
      the porous layer of aluminum oxide, which is formed on the metal surfaces. In
      this work, the optimum conditions for the preparation and conditioning of fibers
      and the extraction of analytes from gaseous samples were obtained. In the optimum
      conditions, one fiber was used in several equal analyses and the relative
      standard deviations were below 5% (n = 5). However, fiber-to-fiber
      reproducibility was 8% (n = 5). This fiber is firm, inexpensive, and durable and
      can be prepared simply.

PMID- 11534737
TI  - Comments on the article "An electrochemical impedance measurement technique
      employing Fourier transform" by J.-S. Yoo and S.-M. Park.

PMID- 11534738
TI  - Life-cycle and dispositional routes into problem debt.
AB  - This paper presents analyses of the correlates of debt in a three-wave panel
      study of saving and other financial behaviour. The data used came from a
      representative sample of Dutch households. The results confirm the findings of
      previous studies on nonrepresentative samples and demonstrate that although
      economic variables alone predict debt quite well, psychological factors
      (especially present orientation, self-control and attitudes towards debt) improve
      our ability to predict indebtedness. The results also suggest that for most
      individuals being in debt is a short-term problem: chronic debtors are a small
      group and are distinguished by having more limited economic and social resources,
      being more present-oriented and finding it more difficult to control their
      expenditure than temporary debtors. Dynamic analyses suggest, however, that many
      of the differences in psychological variables between debtors and non-debtors may
      be a consequence of being in debt rather than a cause of it.

PMID- 11534739
TI  - Psychological perspective on human developmental stability and fluctuating
      asymmetry: sources, applications and implications.
AB  - In recent years researchers from diverse disciplines in the life sciences have
      turned their attention to the issue of developmental stability in the organism.
      Their key measure, fluctuating asymmetry (FA), is defined as the random, stress
      induced deviations from perfect symmetry that develop during the development of
      bilaterally symmetrical traits. This is regarded as a promising measure of the
      stress experienced by individuals during their development, as well as the
      interaction between genetic and environmental forces which affect that
      development. FA also sheds light on several domains within psychological
      research, such as the interplay between nature and nurture during human
      development, etiology of mental health, mating and choice of partners, and even
      perception of facial beauty. This study reviews the manifestation and sources of
      FA in humans, and seeks to provide some insight regarding their relevance and
      possible application to various domains in psychology.

PMID- 11534740
TI  - The role of time pressure on the emotional stroop task.
AB  - Although a wide range of methodologies have been employed in examining the
      emotional Stroop effect, little systematic investigation of these experimental
      manipulations has taken place. Two experiments were designed to investigate the
      role of time pressure in the emotional Stroop effect. It is shown that time
      pressure has an important role to play in determining not only the magnitude of
      the effect but also in whether it is possible to observe any effect at all.

PMID- 11534741
TI  - Inhibitory effects during object name retrieval: the effect of interval between
      prime and target on picture naming responses.
AB  - Three picture naming experiments are reported which examine the relationship
      between the apparent inhibition of a response on one trial, and naming latency on
      the subsequent trial. The design of each experiment involves the presentation of
      prime and target pairs, either presented in succession (Lag 1 condition), or
      separated by two intervening unrelated trials (Lag 3 condition). A control
      condition is also included. In Experiment 1, a speeded picture naming task is
      used, and naming errors are analysed. Target pictures are misnamed at above
      chance rates with the name of the semantically related prime picture in the Lag 3
      condition. In contrast, these prime-related errors do not occur in the Lag 1
      condition, suggesting a brief inhibitory effect. If primes are briefly inhibited,
      then target naming latencies immediately following a related prime should be
      quicker than target latencies in the Lag 3 condition. Experiment 2 confirms this
      pattern of results, using exactly the same stimuli and design, but standard
      naming instructions. Experiment 3 examines whether the inferred inhibition is the
      result of a self-inhibitory mechanism, using a repetition priming paradigm. If
      Lag 1 prime representations are self-inhibited, then facilitatory effects from
      prime/target repetition should be stronger in the Lag 3 condition, than in the
      Lag 1 condition. The data from Expt 3 were not consistent with this prediction.
      Taken together, the results of the three experiments suggest that a brief
      inhibitory effect occurs after retrieval of an object name, and that the
      inhibition may be accomplished by mechanisms other than self-inhibition.

PMID- 11534742
TI  - Anger on and off the road.
AB  - Participants reported on two recent experiences of anger, of which one had
      occurred while they were driving and the other in a non-driving situation. Anger
      while driving was described as less mixed with other emotions, involving purer
      appraisals of other-blame, more likely to be caused by communication
      difficulties, and slower to be noticed by the person who was its target. Levels
      of negative affect preceding anger were rated as significantly lower in driving
      than non-driving situations, and mood and unrelated pressure were considered to
      be less influential causes of the subsequent emotional reaction. Frequency
      estimates supported the popular notion that anger is relatively more likely while
      driving than during other activities. Individual difference measures relating to
      ambivalence over emotional expression, self-consciousness, and empathy showed no
      reliable correlations with frequency of anger while driving, but previously
      developed self-report indices of driving anger and aggression made a significant
      contribution to its prediction even after controlling for anger frequency in
      other situations. These results support everyday intuitions that certain features
      of the road situation differentially predispose drivers to become angry and that
      the resulting anger tends to take a different form from anger experienced off the
      road.

PMID- 11534743
TI  - Discrimination of spatial relations and features in faces: effects of inversion
      and viewing duration.
AB  - We studied discrimination of changes in eye position, mouth position, and eye
      colour at viewing durations ranging from 1 second to unlimited time. With upright
      faces, perception was rapid and did not improve above 2 seconds viewing time.
      Face inversion impaired discrimination of mouth position significantly, eye
      position slightly, but not eye colour. The 'inversion effect' for mouth position
      decreased with increasing stimulus duration, and disappeared when the subject
      knew that the only change in a trial was in mouth position. A subsequent
      experiment showed that the inversion impairment in the mouth region was not
      specific to spatial position but affected mouth colour to a lesser degree. When
      the mouth region was made more salient by increasing the frequency of mouth
      change trials, the inversion effect for mouth position decreased, and correlated
      with an increase in inversion effect for eye position but not eye colour. We
      conclude that the dominant effect of face inversion upon perception is decreased
      discrimination in less salient facial regions, that this impairment lessens with
      increasing viewing time, and that it affects both features and their spatial
      relations, though the effect on the latter is greater. These results are
      consistent with greater dependence on a serial component search strategy in
      inverted faces.

PMID- 11534744
TI  - Dysexecutive symptoms among a non-clinical sample: a study with the use of the
      Dysexecutive Questionnaire.
AB  - Clinical studies indicate that damage to the frontal lobes may lead to a set of
      symptoms collectively known as 'Dysexecutive syndrome', which is characterized by
      changes in emotion, personality, motivation, behaviour and cognitive aspects.
      Factor analytical study using questionnaires measuring dysexecutive problems in
      everyday life also suggests a fractionation of the dysexecutive syndrome among
      patients with neurological disorders. As yet, very little research has been
      conducted to explore the base-rate of executive problems in everyday life among
      the non-clinical population. This pilot study aimed to explore dysexecutive
      behaviour similar to that of dysexecutive syndrome reported by a non-clinical
      sample. A total of 93 presumably normal participants were recruited. The
      Dysexecutive Questionnaire and a set of clinical tests of executive function were
      administered to all the participants. A 5-factor solution very similar to that of
      a previous study was derived: inhibition (factor 1), intentionality (factor 2),
      knowing-doing dissociation (factor 3), in-resistance (factor 4), and social
      regulation (factor 5). Correlation was established among the derived factors and
      tests of executive function. This study provides empirical evidence that a non
      clinical sample may encounter similar dysexecutive behaviours in daily life. The
      issue of the fractionation of the executive system among the non-clinical sample
      will also be discussed.

PMID- 11534745
TI  - U.S. Public Health Service Guideline on Infectious Disease Issues in
      Xenotransplantation. Centers for Disease Control and Prevention.
AB  - Several developments have fueled the renewed interest in xenotransplantation--the
      use of live animal cells, tissues and organs in the treatment or mitigation of
      human disease. The world-wide, critical shortage of human organs available for
      transplantation and advances in genetic engineering and in the immunology and
      biology of organ/tissue rejection have renewed scientists' interest in
      investigating xenotransplantation as a potentially promising means to treat a
      wide range of human disorders. This situation is highlighted by the fact that in
      the United States alone, 13 patients die each day waiting to receive a life
      saving transplant to replace a diseased vital organ.

PMID- 11534746
TI  - Oral hygiene and lifestyle correlates among new undergraduate university students
      in Lebanon.
AB  - Little is known about Lebanese college students' oral hygiene and the factors
      associated with how often they brush their teeth. The authors used a structured
      questionnaire to investigate these issues in a sample of 954 new students at the
      American University of Beirut in fall 1998. The results indicated poor flossing
      habits and unfavorable dietary habits among the group. Moreover, using logistic
      regression analysis, they found that variables such as gender, father's
      education, exercise, and dietary habits, were significantly correlated with the
      how frequently the students brushed their teeth. Appropriate promotional
      activities to improve flossing and dietary habits associated with better oral
      hygiene are recommended. In addition, the authors call for further research to
      elaborate on the deficiencies in oral health practices and explore a wider
      variety of lifestyle behaviors and their correlation.

PMID- 11534747
TI  - Internet use among college students: an exploratory study.
AB  - The author and associates surveyed 1,300 college students in classrooms at eight
      academic institutions to identify how the students' use of the Internet has
      affected their social or academic lives. Although the typical Internet-using
      student uses the Internet for 100 minutes per day, a small group of students use
      the Internet to a degree that interferes with other aspects of their lives. Most
      of them are men and are found among the hard science academic majors. Some ideas
      for dealing with this problem are suggested.

PMID- 11534748
TI  - Consumers' self-care algorithms for the common cold: implications for health
      education interventions.
AB  - Two hundred ninety-seven young adults enumerated a self-care plan with at least
      seven behaviors for the management of a cold with a fever. They summarized
      satisfaction with their self-care activities and the role of self-care after a
      lecture on self-care in managing the common cold. Half of the participants relied
      solely on self-care, and the other half said they would seek medical attention.
      Having a fever directed two thirds of the sample in their decision making
      concerning treatment. Five percent would change their self-care behaviors as a
      consequence of the instruction. Methodological and theoretical implications for
      self-care interventions are discussed.

PMID- 11534749
TI  - Binge drinking among undergraduate college students in the United States:
      implications for other substance use.
AB  - The authors examined the relationship between binge drinking and other substance
      use among US college students, using nationally representative data from the 1995
      National College Health Risk Behavior Survey implemented by the Centers for
      Disease Control and Prevention. Compared with nonbinge drinkers, current binge
      drinkers were significantly more likely to report "ever" using and current use of
      cigarettes, marijuana, cocaine, and other illegal drugs. The researchers also
      found that the more often students binge drank, the more likely they were to have
      ever used cigarettes, marijuana, cocaine, and other drugs, and the more likely
      they were to report current use of cigarettes and marijuana. Those who design
      programs to prevent binge drinking and use of other substances should take into
      account the reality that many students use more than one substance and that the
      more frequently students report binge drinking, the more likely they are to be
      using other substances as well.

PMID- 11534750
TI  - Urging college alcohol and drug policies that target adverse behavior, not use.
AB  - Although "zero tolerance" policies are being enacted on campuses nationwide,
      these policies may not be the most effective means of creating safer and
      healthier environments for students. Many historical precedents illustrate the
      value of moderation over prohibition. College drug and alcohol policies should
      focus primarily on dysfunctional and disruptive student behaviors, not on student
      drug and alcohol use only.

PMID- 11534751
TI  - Human resource issues in university health services.
AB  - To provide first-rate services to students, college health services need the best
      possible staff. Managers and supervisors play a critical role in guiding the work
      of their employees so as to enhance performance. Reference checks for new
      employees and regular performance appraisal dialogues for ongoing employees are
      important tools in this process. The author discusses these issues and suggests
      formats for reference checks and performance appraisals.

PMID- 11534752
TI  - Why and how to publish research in the Journal of American College Health.

PMID- 11534753
TI  - Antibiotic-seeking behavior in college students: what do they really expect?
AB  - Injudicious use of antibiotics contributes to increased bacterial resistance, and
      patient expectations encourage physicians to overuse antibiotics. The authors
      evaluated the level of ill college students' antibiotic-seeking behavior to
      determine if receiving an antibiotic prescription influenced patients'
      satisfaction with visits to a clinician. Of 129 students with upper respiratory
      complaints presenting to a university health center, 55% expected an antibiotic
      prescription. Antibiotic expectation was significantly more likely among students
      who thought they had a bacterial versus a viral infection (90% vs 40%; p < .01).
      A clear diagnosis, an explanation of the rationale for treatment, and an
      antibiotic prescription were significantly associated with patient satisfaction.
      Clinicians prescribed an antibiotic for 36% of the students; only 13% of these 46
      had requested an antibiotic during the visit. At some previous time, one third of
      the students had taken an antibiotic prescribed for an earlier illness or for
      another person. Better patient education and improved clinician-patient
      communication can potentially help to reduce the injudicious use of antibiotics.

PMID- 11534754
TI  - Facile synthesis and biological evaluation of heterocyclic compounds containing
      diazepam.
AB  - Diazepamoxadiazoles 4, 5, 6, 12, 14 and 22 were prepared with the binary form
      system. Diazepamthiadiazoles 15, 20 and Diazepamtriazoles 7, 8, 9, 17, 18, 19 and
      21 were also shapely synthesized. Some of these compounds were screened to test
      their antibacterial activity against E. coli and B. subtilis compounds 15 and 20
      show potent activity against these bacteria.

PMID- 11534755
TI  - 4-Hydroxy-6-oxo-6,7-dihydro-thieno[2,3-b] pyrimidine derivatives: synthesis and
      their biological evaluation for the glycine site acting on the N-methyl-D
      aspartate (NMDA) receptor.
AB  - Bioisostere approach has been shown to be useful to augment potency or to modify
      certain physiological properties of a lead compound. Based upon well documented
      bioisosterism, an isosteric replacement of benzene ring of 4-hydroxy-2-quinolone
      compound (L-695902) with a thiophene moiety was carried out to prepare the title
      compounds, 4-hydroxy-6-oxo-6,7-dihydro-thieno[2,3-b] pyrimidines 15. The
      resulting bioisosteric compounds 15 were evaluated for their antagonistic
      activity (binding assay) for NMDA receptor glycine site.

PMID- 11534756
TI  - Structure-activity relationship studies of isoquinolinone type anticancer agent.
AB  - Substituted isoquinolin-1-ones (1) were synthesized to test their in vitro
      anticancer activity. 3-Biphenyl-N-methylisoquinolin-1-one (7) showed the most
      potent anticancer activity against five different human cancer cell lines.

PMID- 11534757
TI  - Chiral separation of beta2-agonists by capillary electrophoresis using
      hydroxypropyl-alpha-cyclodextrin as a chiral selector.
AB  - Enantiomers of five racemic beta2-agonists were investigated by capillary
      electrophoresis employing a hydroxypropyl-beta-cyclodextrin (HP-beta-CD). The
      effects of the concentration of HP-beta-CD added to the background electrolyte
      and of the pH of the buffer on the effective mobility and resolution of the
      studied compounds were examined. Very good resolution was achieved for
      terbutaline and clenbuterol; salbutamol and bambuterol was able to be partially
      resolved. Enantioselectivity and resolution were influenced by the concentration
      of the HP-beta-CD, buffer composition and pH.

PMID- 11534758
TI  - HIV-1 integrase inhibitory phenylpropanoid glycosides from Clerodendron
      trichotomum.
AB  - Seven phenylpropanoid glycosides named acteoside (1), acteoside isomer (2),
      leucosceptoside A (3), plantainoside C (4), jionoside D (5), martynoside (6), and
      isomartynoside (7) were isolated from Clerodendron trichotomum. Compounds 1 and 2
      showed potent inhibitory activities against HIV-1 integrase with IC50 values of
      7.8 +/- 3.6 and 13.7 +/- 6.0 microM, respectively.

PMID- 11534759
TI  - Prolyl endopeptidase inhibitors from green tea.
AB  - Three prolyl endopeptidase (PEP) inhibitors were isolated from the methanolic
      extract of green tea leaves. They were identified as (-)-epigallocatechin
      gallate, (-)-epicatechin gallate, and (+)-gallocatechin gallate with the IC50
      values of 1.42 x 10(-4) mM, 1.02 x 10(-2) mM, and 1.09 x 10(-4) mM, respectively.
      They were non-competitive with a substrate in Dixon plots and did not show any
      significant effects against other serine proteases such as elastase, trypsin, and
      chymotrypsin, suggesting that they were relatively specific inhibitors against
      PEP. The isolated compounds are expected to be useful for preventing and curing
      of Alzheimer's disease.

PMID- 11534760
TI  - In vitro anti-Helicobacter pylori activity of panaxytriol isolated from ginseng.
AB  - This study investigated the effect that some polyacetylenes and protopanaxatriol,
      which were isolated from heated ginseng (family Araliaceae), have on inhibiting
      Helicobacter pylori (HP) growth. Among the compounds tested, panaxytriol was
      quite effective in inhibiting HP growth with an MIC of 50 microg/ml. Ginsenoside
      Rh1 and protopanaxatriol weakly inhibited H+/K+-ATPase from a rat stomach.

PMID- 11534761
TI  - Annomocherin, annonacin and annomontacin: a novel and two known bioactive mono
      tetrahydrofuran annonaceous acetogenins from Annona cherimolia seeds.
AB  - A novel and two known bioactive mono-tetrahydrofuran (THF) annonaceous
      acetogenins, annomocherin (1), annonacin (2) and annomontacin (3), have been
      isolated from the fractionated ethanolic extracts of the seeds of Annona
      cherimolia, guided by the brine shrimp lethality test (BST). Their structures
      were elucidated on the basis of spectroscopic and chemical methods. All compounds
      have a relative stereochemistry of threo/trans/threo for the mono-THF ring with
      two flanking hydroxyls. Compound 1 has a double bond at C-23/24 of aliphatic
      chain. Compound 1 was isolated from natural sources for the first time, and was
      named annomocherin. Two known Compounds 2 and 3 which have never been isolated
      from this species before, were obtained. Compound 1 exhibited potent and
      selective cytotoxicities against the breast carcinoma (MCF-7) and kidney
      carcinoma (A-498) cell lines with 100 to 1,000 times the potency of adriamycin.
      In brine shrimp lethality test (BST), 1-3 exhibited cytotoxicity.

PMID- 11534762
TI  - Kojic acid, a potential inhibitor of NF-kappaB activation in transfectant human
      HaCaT and SCC-13 cells.
AB  - The activation of NF-kappaB induced by kojic acid, an inhibitor of tyrosinase for
      biosynthesis of melanin in melanocytes, was investigated in human transfectant
      HaCaT and SCC-13 cells. These two keratinocyte cell lines transfected with pNF
      kappaB-SEAP-NPT plasmid were used to determine the activation of NF-kappaB.
      Transfectant cells release the secretory alkaline phosphatase (SEAP) as a
      transcription reporter in response to the NF-kappaB activity and contain the
      neomycin phosphotransferase (NPT) gene for the dominant selective marker of
      geneticin resistance. NF-kappaB activation was measured in the SEAP reporter gene
      assay using a fluorescence detection method. Kojic acid showed the inhibition of
      cellular NF-kappaB activity in both human keratinocyte transfectants. It could
      also downregulate the ultraviolet ray (UVR)-induced activation of NF-kappaB
      expression in transfectant HaCaT cells. Moreover, the inhibitory activity of
      kojic acid in transfectant HaCaT cells was found to be more potent than known
      antioxidants, e.g., vitamin C and N-acetyl-L-cysteine. These results indicate
      that kojic acid is a potential inhibitor of NF-kappaB activation in human
      keratinocytes, and suggest the hypothesis that NF-kappaB activation may be
      involved in kojic acid induced anti-melanogenic effect.

PMID- 11534763
TI  - Phytochemical constituents of Artemisia stolonifera.
AB  - Repeated column chromatographic separation of the CH2Cl2 extract of Artemisia
      stolonifera (Asteraceae) led to the isolation of a triterpene (I), a
      sesquiterpene (II), two aromatic compounds (III and IV) and a benzoquinone (V).
      Their structures were determined by spectroscopic means to be simiarenol (I),
      (1S,7S)-1beta-hydroxygermacra-4(15),5,10(14)-triene (II), 3'-methoxy-4'-hydroxy
      trans-cinnamaldehyde (III), vanillin (IV) and 2,6-dimethoxy-1,4-benzoquinone (V),
      respectively. Among these products, compound V showed significant cytotoxicity
      against five human tumor cell lines in vitro, A549 (non small cell lung
      adenocarcinoma), SK-OV-3 (ovarian), SK-MEL-2 (skin melanoma), XF498 (CNS) and
      HCT15 (colon) with ED50 values ranging from 1.33-4.22 microg/ml.

PMID- 11534764
TI  - Cloning, sequence analysis, and characterization of the astA gene encoding an
      arylsulfate sulfotransferase from Citrobacter freundii.
AB  - Arylsulfate sulfotransferase (ASST) transfers a sulfate group from a phenolic
      sulfate ester to a phenolic acceptor substrate. In the present study, the gene
      encoding ASST was cloned from a genomic library copy of Citrobacter freundii,
      subcloned into the vector pGEM3Zf(-) and sequenced. Sequencing revealed two
      contiguous open reading frames (ORF1 and ORF2) on the same strand and based on
      amino acid sequence homology, they were designated as astA and dsbA,
      respectively. The amino acid sequence of astA deduced from C. freundii was highly
      similar to that of the Salmonella typhimurium, Enterobacter amnigenus,
      Klebsiella, Pseudomonas putida, and Campylobacter jejuni, encoded by the astA
      genes. However, the ASST activity assay revealed different acceptor
      specificities. Using p-nitrophenyl sulfate (PNS) as a donor substrate, alpha
      naphthol was found to be the best acceptor substrate, followed by phenol,
      resorcinol, p-acetaminophen, tyramine and tyrosine.

PMID- 11534765
TI  - In vivo antitumor efficacy of CW252053, a folate-based thymidylate synthase
      inhibitor.
AB  - Previous studies have demonstrated that CW252053, a quinazoline antifolate,
      exhibits potent inhibitory activity against thymidylate synthase (TS) as well as
      cytotoxic activity against tumor cell lines in vitro. In this study, we evaluated
      the in vivo antitumor efficacy of CW252053 in the mouse tumor model. Female
      B6D2F1 mice were injected with LY3.7.2C TK-/- (thymidine kinase deficient mouse
      lymphoma) cells into the gastrocnemius muscle. Then, CW252053 was administered
      twice daily by intraperitoneal injection for 10 days, and tumor growth was
      monitored daily by leg diameter measurement. All animals in the vehicle, 5-FU,
      and low dose (30 mg/kg) CW252053 treated groups died between days 12 and 23
      because of the tumor burden. In contrast, dosing with 60 mg/kg of CW252053
      produced a cure rate against tumor growth of 37.5% and a survival rate of 50%.
      Even more significantly, a higher dose of CW252053 (120 mg/kg) elicited both a
      100% cure rate and a 100% survival rate at the termination of the study,
      confirming that this compound has very potent in vivo antitumor activity against
      tumor growth. During the experimental period of this study no signs of toxicity
      were observed even at the high CW252053 dosage rate of 120 mg/kg.

PMID- 11534766
TI  - Antifibrotic effect of extracellular biopolymer from submerged mycelial cultures
      of Cordyceps militaris on liver fibrosis induced by bile duct ligation and
      scission in rats.
AB  - The antifibrotic effects of hot water extract (WEC), intracellular biopolymer
      (IPC) and extracellular biopolymers (EPC) from mycelial liquid culture of
      Cordyceps militaris on liver fibrosis were studied. Liver fibrosis was induced by
      a bile duct ligation and scission (BDL/S) operation, duration of 4 weeks in rats.
      In BDL/S rats, the levels of aspartate transaminase (AST), alanine transaminase
      (ALT), alkaline phosphatase (ALP), total bilirubin in serum and hydroxyproline
      content in liver were dramatically increased. The WEC or IPC treatment (30
      mg/kg/day for 4 weeks, p.o.) in BDL/S rats reduced the serum AST, ALT and ALP
      levels significantly (p<0.01). The EPC treatment (30 mg/kg/day for 4 weeks, p.o.)
      reduced the serum ALT, AST and ALP levels significantly (p<0.01). Malondialdehyde
      contents in liver treated with WEC, IPC or EPC were significantly reduced
      (p<0.05). But Liver hydroxyproline content was decreased only in EPC treated
      BDL/S rats to 55% that of BDL/S control rats (p<0.01). The morphological
      characteristics and expression of alpha smooth muscle like actin in fibrotic
      liver, which appeared in BDL/S control group were improved in EPC treated
      fibrotic liver. These results indicate that EPC (30 mg/kg/day for 4 weeks, p.o.)
      has an antifibrotic effect on fibrotic rats induced by BDL/S.

PMID- 11534767
TI  - Pharmacokinetics of diltiazem and its major metabolite, deacetyidiltiazem after
      oral administration of diltiazem in mild and medium folate-induced renal failure
      rabbits.
AB  - The pharmacokinetic changes of diltiazem (DTZ) and its main metabolite,
      deacetyldiltiazem (DAD) were studied after oral administration of DTZ to normal
      rabbits and mild and medium folate-induced renal failure rabbits. DTZ 10 mg/kg
      was given to the rabbits either orally (n=6). Plasma concentrations of DTZ and
      DAD were determined by a high performance liquid chromatography assay. The area
      under the plasma concentration-time curves (AUC) and maximum plasma concentration
      (Cmax) of DTZ were significantly increased in mild and medium folate-induced
      renal failure rabbits. The metabolite ratio of the DTZ to DAD were significantly
      decreased in mild and medium folate-induced renal failure rabbits. The volume of
      distribution (Vd) and total body clearance (CLt) of DTZ were significantly
      decreased in mild and medium folate-induced renal failure rabbits. The
      elimination rate constant (beta) of DTZ was significantly decreased in folate
      induced renal failure rabbits, but that of DAD was significantly increased. These
      findings suggest that the hepatic metabolism of DTZ was inhibited and the Vd, CLt
      and beta of DTZ were significantly decreased in mild and medium folate-induced
      renal failure rabbits.

PMID- 11534768
TI  - Circadian changes in pharmacokinetics of sulfamethoxazole administered orally to
      rabbits.
AB  - Circadian variations of sulfamethoxazole pharmacokinetics were studied after a
      single oral administration of sulfamethoxazole, 50 mg/kg, to rabbits at 09:00
      (a.m.) and 22:00 (p.m.). The profiles of plasma sulfamethoxazole concentration
      showed from 6 h to 24 h significant statistical difference (p<0.05) between 09:00
      and 22:00. The half-life (t(1/2)) was significantly shorter in the morning (11.2
      +/- 3.2 h) when compared to the nighttime (15.4 +/- 3.5 h) (p< 0.05). The AUC was
      significantly decreased in the morning (1325 +/- 264 microg/ml x h) than that in
      the nighttime (2059 +/- 379 microg/ml x h) (p<0.05). Total body clearance (CLt)
      was significantly higher when sulfamethoxazole was given in the morning (6.65 +/-
      0.23 ml/min) versus in the nighttime (4.28 +/- 0.20 ml/min) (p<0.05).

PMID- 11534770
TI  - Inhibition of invasion and induction of apoptosis by curcumin in H-ras
      transformed MCF10A human breast epithelial cells.
AB  - Curcumin, a dietary pigment in turmeric, posseses anti-carcinogenic and anti
      metastatic properties. The present study was conducted to study in vitro
      chemopreventive effects of curcumin in transformed breast cells. Here, we show
      that curcumin inhibits H-ras-induced invasive phenotype in MCF10A human breast
      epithelial cells (H-ras MCF10A) and downregulates matrix metalloproteinase (MMP)
      2 dose-dependently. Curcumin exerted cytotoxic effect on H-ras MCF10A cells in a
      concentration-dependent manner. Curcumin-induced cell death was mainly due to
      apoptosis in which a prominent downregulation of Bcl-2 and upregulation of Bax
      were involved. We also suggest a possible involvement of caspase-3 in curcumin
      induced apoptosis. Curcumin treatment resulted in the production of reactive
      oxygen species (ROS) in H-ras MCF10A cells. Apoptotic event by curcumin was
      significantly inhibited by pretreatment of an antioxidant N-acetyl-L-cysteine
      (NAC), suggesting redox signaling as a mechanism responsible for curcumin-induced
      apoptosis in H-ras MCF10A cells. Taken together, our results demonstrate that
      curcumin inhibits invasion and induces apoptosis, proving the chemopreventive
      potential of curcumin.

PMID- 11534769
TI  - Apoptosis-Inducing costunolide and a novel acyclic monoterpene from the stem bark
      of Magnolia sieboldii.
AB  - In a course of obtaining more amount of bioactive costunolide and successive
      phytochemical isolation from Magnolia sieboldii (Magnoliaceae), a novel acyclic
      monoterpene 1 named deoxygeraniol [2,6(E)-dimethyl-2,6-octadiene] was isolated
      along with beta-sitosterol 3-O-linoleate (2), trilinolein (3) and high amount of
      costunolide (4) in the pure state. The structure of compound 1 was determined on
      the basis of spectroscopic data. Costunolide was found to induce apoptotic cell
      death in a dose-dependent manner by nucleosomal DNA ladder and flow cytometric
      analysis. Immunoblot analysis showed that the level of the anti-apoptotic
      protein, Bcl-2, was decreased, whereas the cleavage of poly-(ADP-ribose)
      polymerase was activated. Furthermore, the N-acetyl-L-cysteine antioxidant
      effectively prevented costunolide-induced cytotoxicity. These results suggest
      that costunolide-induced cell death is mediated by reactive oxygen species

PMID- 11534771
TI  - Determination of recombinant human epidermal growth factor (rhEGF) in a
      pharmaceutical formulation by high performance liquid chromatography with
      electrochemical detection.
AB  - A novel HPLC method with electrochemical detection has been developed for the
      determination of recombinant human epidermal growth factor (rhEGF) in
      pharmaceutical products. rhEGF was separated from other components in formulation
      on a reversed-phase C18 column with 24% acetonitrile in 0.1 M phosphate buffer
      (pH 4.75). The optimum electrochemical oxidation of EGF was obtained at 0.85 V
      vs. Ag/AgCl in a glassy carbon working electrode due to electroactive tyrosine,
      tryptophan, methionine, and arginine residues. The quantitation range was from
      1.0 to 200 ng of rhEGF with the linear correlation coefficient greater than
      0.999. The method was successfully applied for the quantitation of rhEGF in a
      pharmaceutical preparation.

PMID- 11534772
TI  - Differential distribution of ganglioside GM3 in seminiferous tubule and
      epididymis of adult rats.
AB  - Gangliosides are ubiquitous membrane components in mammalian cells and are
      suggested to play important roles in various functions such as cell-cell
      interaction, adhesion, cell differentiation, growth control and signaling. Among
      all ganglio-series gangliosides, GM3 has the simplest carbohydrate structure, and
      has been shown as a major ganglioside in male reproductive system. To study GM3
      distribution in the seminiferous tubule and epididymis, frozen sections were
      stained with specific monoclonal antibody (MAb) against ganglioside GM3. In the
      seminiferous tubule of testis, pachytene spermatocytes and spermatids expressed
      ganglioside GM3, but not in spermatogonia and sertoli cells. Spermatogonia and
      sertoli cells near the basement membrane were negatively reacted to anti-GM3. In
      the epididymis, GM3 was expressed only in some interstitial cells. Taken
      together, these results suggest that the expression of ganglioside GM3 in rat
      seminiferous tubule and epididymis is spatio-temporally regulated during
      spermatogenesis.

PMID- 11534773
TI  - Spatial summation of heat pain in males and females.
AB  - Sex differences in pain sensitivity have been found to vary between considerable
      and negligible. It has appeared that the pain stimulation method is critical in
      this context. It was assumed this might be due to the different degrees of
      spatial summation associated with the different pain stimulus modalities. Hence,
      sex differences were investigated in spatial summation of heat pain in 20 healthy
      women and 20 healthy men of similar age. Pain thresholds were assessed by a
      tracking procedure and responses to supra-threshold pain stimulation by numerical
      ratings. Heat stimuli were administered by a thermode with contact areas of 1, 3,
      6 and 10 cm2. Pain thresholds were significantly higher with smaller areas
      stimulated than with larger ones. No significant effect of area was found for the
      ratings of the supra-threshold stimuli, the intensities of which were tailored to
      the individual pain threshold. Consequently, spatial summation of heat pain
      appeared to result mainly in a shift of the pain threshold on the ordinate and
      not a change of slope of the stimulus-response function in the pain range. In
      neither of the two pain parameters were there any sex differences. Therefore, the
      present study demonstrated that sex differences in spatial summation of heat pain
      are unlikely.

PMID- 11534774
TI  - Serial recording of sensory, corticomotor, and brainstem-derived motor evoked
      potentials in the rat.
AB  - A method is presented for serial recording of corticomotor evoked potentials
      (CMEPs), brainstem-derived motor evoked potentials (BMEPs), and somatosensory
      evoked potentials (SEPs) via permanently implanted cranial screws. One screw was
      positioned posterior to lambda (posterior screw), and two screws were positioned
      over the cortical hind limb areas (cortical screws). SEPs were elicited by
      stimulation of the hind paw and recorded from the contralateral cortex. BMEPs
      were stimulated via the posterior screw and recorded from both hind limbs,
      whereas CMEPs were elicited by repeated bipolar stimulation of the cortex and
      recorded from the contralateral hind limb. BMEPs and CMEPs differed in several
      points and can be considered as completely separate motor evoked potentials.
      While BMEPs consisted of a prominent negative peak with short latency (5-7.5 ms),
      CMEPs were represented by polyphasic signals with long latencies (17-22 ms). The
      cortical origin of the CMEPs was confirmed by transecting the corticospinal
      tracts, which abolished the CMEPs but spared the BMEPs. SEPs consisted of three
      consecutive peaks with mean latencies of the initial peak ranging between 15 and
      17 ms. Dorsal column transection also abolished SEPs. In healthy rats, all three
      signals were recorded for six consecutive weeks. Signal parameters did not change
      significantly within this observation period. Rats tolerated the screws and the
      repeated measurements very well and no negative affect on animal behavior was
      noted. Thus, this method allows serial recording of SEPs, CMEPs, and BMEPs in
      chronic rat models.

PMID- 11534775
TI  - Corticotectal and corticostriatal projections from the frontal eye fields of the
      cat: an anatomical examination using WGA-HRP.
AB  - Corticofugal projections from the frontal eye fields (FEF) are believed to access
      the superior colliculus (SC) directly (i.e., monosynaptically) and indirectly
      (i.e., multisynaptically) through the basal ganglia. The present results suggest
      that these two pathways are derived from largely segregated populations of
      corticofugal neurons. Furthermore, while the different subregions of the FEF from
      which these pathways originate have different termination patterns in the basal
      ganglia (i.e., striatum, ST), they share a common termination pattern in the SC.
      Injections of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) into the two
      major subdivisions of the FEF (presylvian and cruciate sulci) resulted in dense
      label in both the ST (bilaterally) and the SC (ipsilaterally). Corticostriatal
      labeling was found in the caudal part of the head of the caudate nucleus
      (heaviest ipsilaterally), with labeling from cruciate injections located
      ventromedial to that produced by presylvian injections. Only presylvian
      injections resulted in labeling in the putamen. Retrograde tracing experiments
      demonstrated that both presylvian and cruciate corticostriatal projections
      originated from neurons in lamina III and the upper aspects of lamina V. An
      additional but small group of presylvian corticostriatal projections was found in
      lamina VI. Corticotectal terminal labeling was restricted to the deep laminae of
      the SC and was derived exclusively from lamina V neurons in cortex. They differed
      from their corticostriatal counterparts in laminar/sub-laminar location and in
      soma sizes.

PMID- 11534776
TI  - An architectonic comparison of the ventrobasal complex of two megachiropteran and
      one microchiropteran bat: implications for the evolution of Chiroptera.
AB  - The architectonic features of the thalamic ventrobasal complex (Vb) of two
      species of Megachiropteran (Grey-headed flying fox, Pteropus poliocephalus, and
      the Eastern tube-nosed bat, Nyctimene robinsoni) are compared with those of a
      Microchiropteran (Australian ghost bat, Macroderma gigas). The somatosensory
      system was chosen for comparison as it represents a sensory system that has
      undergone analogous modifications in both Chiropteran lineages (the evolution of
      the wing). The components of Vb were examined as there are taxon-specific
      features in this region of the brain. Within the Megachiropteran Vb, four
      subnuclei were recognized: the ventral posterior medial (VPM), the ventral
      posterior lateral (VPL), the ventral posterior inferior (VPI), and the basal
      ventral medial (VMb). In the ghost bat only VPM and VPL were identified with
      certainty. No VPI was evident in the ghost bat, however a putative VMb was
      observed. Vb of the ghost bat also lacked the arcuate lamina, which distinguishes
      VPM from VPL in the Megachiropterans and many other mammals. These taxon-specific
      differences lend support to the proposal that the order Chiroptera has a
      diphyletic origin.

PMID- 11534777
TI  - Periodontal mechanoreceptor input reduces synchronous discharge of voluntarily
      activated masseter motor units in man.
AB  - The control exerted by inputs from periodontal mechanoreceptors (PMRs) on the
      tonic activity of 35 pairs of single motor units in the left masseter muscle was
      investigated with and without the presence of continuous pressure on the upper
      left central incisor tooth. Cross-correlograms were computed to assess the
      temporal coupling between the discharges of the motor unit pairs. In the absence
      of continuous pressure, central peaks in the cross-correlograms revealed the
      presence of significant synchronous discharge in 16 out of the 35 pairs tested.
      In contrast, during PMR stimulation only nine pairs were found to discharge with
      a significant amount of synchronization. It is concluded that short-term
      synchronization due to common, partially common and synchronized inputs shared by
      the motoneurons was reduced whenever extraneous periodontal inputs were
      superimposed on the voluntary command. This indicates that the interneurons which
      mediate the periodontal inputs arising from one single tooth are not distributed
      widely throughout the masseter motoneuron pool. In contrast, it appears that
      periodontal inputs are liable to reduce the efficiency of common inputs
      distributed to the masseter motoneurons during voluntary contraction
      ("desynchronization").

PMID- 11534778
TI  - Temporal organization of multi-whisker contact in rats.
AB  - Previous work has established that during exploration and discrimination, rats
      move their whiskers at frequencies between 6 and 12 Hz and that whisking
      frequency changes during contact. One critical component of any tactile system is
      contact. In the rat whisker system, such contacts may involve one or more
      vibrissa in the whisker array and contact duration of each whisker may vary over
      a considerable range, depending upon the behavioral context. However, little is
      known about the variables controlling contact duration or about the temporal
      relationships among contacts by adjacent whiskers. To address these issues head
      fixed rats were trained to touch a piezo-contact-sensor with the shaft of their
      whiskers (Bermejo and Zeigler, Somatosens Mot Res 17: 373-377, 2000). During the
      task, whisker movements and contacts were monitored with a high-speed camera at
      500 frames/s and stored on videotape. To facilitate analysis, animals had their
      whiskers selectively trimmed. Data are reported from animals with C1 & C2, D1 &
      D2, or Arc2 (E2, D2, C2, B2) whiskers intact. For both row and arc animals, when
      just a single whisker touched the sensor the duration of contact was
      significantly shorter than when multiple whiskers made contact. When multiple
      whiskers made contact, onset was rarely simultaneous. Furthermore, in row-intact
      animals, contact progressed in an orderly fashion such that the rostral whisker
      in a row made contact first followed 24 ms (SE = 1.9 ms) later by the caudal
      whisker. When contact reversed the caudal whisker lifted off first, followed by
      the rostral whisker. Thus, the order in which whiskers touch an object regulates
      contact duration: the first whisker to touch the sensor stays in contact longer
      than any other whisker. The temporal discharge properties of neurons in the
      trigeminal system are expected to reflect position of whiskers on the nose.

PMID- 11534780
TI  - Evaluation of mouse preimplantation embryos cultured in media enriched with
      insulin-like growth factors I and II, epidermal growth factor and tumor necrosis
      factor alpha.
AB  - Culture of preimplantation embryos is complex and requires strictly defined
      culture media to sustain their viability and quality. In the current study, an
      effort was made to evaluate comprehensively the quality of mice embryos, grown in
      media enriched with IGF I, IGF II, EGF and TNFalpha. For that purpose, critically
      chosen and thoroughly described, complex morphological methods based on contrast
      phase, fluorescent and confocal microscopy were used. The study evaluated
      blastulation and hatching rates, total blastocyst cells, inner cell mass cell
      numbers (differential staining) as well as identified embryo cells with positive
      reactions for necrosis or apoptosis (TUNEL). The critical evaluation of the
      effects of the studied cytokines allowed for simultaneous, meticulous assessment
      of the applied study methods. Significantly more blastocysts were found in
      culture media enriched with IGF-I, IGF II and EGF. Significantly more hatched
      blastocysts were found in media with IGF-I and IGF II. Additionally, IGF I and II
      increased inner cell mass and total blastocyst cell numbers. Very few cells with
      necrosis and apoptosis were found in the culture media enriched with IGF I, IGF
      II and EGF. TNFalpha produced negative effects. The observed effects were dose
      dependent.

PMID- 11534779
TI  - Biological significance of chemokine receptor expression by normal human
      megakaryoblasts.
AB  - The aim of this study was to learn more on the role of chemokines in the
      regulation of human megakryopoiesis. Normal human megakaryoblasts were expanded
      in serum-free liquid cultures and subsequently (1) phenotyped for expression of
      various chemokine receptors, (2) evaluated if chemokine receptors which they
      express are functional after stimulation by chemokines (calcium flux assay,
      chemotaxis, phosphorylation of MAPK-p42/44 and AKT proteins), and (3)
      investigated for expression and secretion of selected chemokines by employing RT
      PCR and ELISA assays, respectively. In addition we also phenotyped peripheral
      blood platelets for expression of chemokine receptors and chemokines. We found
      that while human megakaryoblasts express several chemokine receptors (CXCR4,
      CCR6, CCR8, CCR5, CCR2 and CXCR3), CXCR4 was the only receptor detectable by FACS
      on human platelets. Moreover, among various chemokines tested, only SDF-1 (CXCR4
      ligand) stimulated calcium flux and chemotaxis in normal human megakaryoblasts
      and phosphorylated MAPK-p42/44 and AKT in these cells. Although mRNAs for several
      chemokines were detectable by RT-PCR in normal human megakaryoblasts, only
      RANTES, IL-8, MCP-1 and PF-4 were found to be secreted by these cells. Finally we
      noticed that no chemokine tested in this study affected CFU-Meg colony formation
      by human CD34+ cells in serum-free cultures. We conclude that from all the
      chemokine receptor-chemokine axes tested, only SDF-1-CXCR4 axis was functional in
      assays employed in our studies, which further support the view that this axis
      plays a privileged role in regulating normal human megakaryopoiesis.

PMID- 11534782
TI  - Ki-67 labelling index in human brain tumours.
AB  - The proliferative potential in 157 brain tumours was investigated using Ki-67
      labelling index (Ki-67LI). There were 46 patients with low grade gliomas (Al &
      All), 82 with high grade gliomas (AIII & AIV) and 29 with metastatic tumours.
      Tumour fragments used for assessment of Ki-67LI were fixed in formalin. Ki-67
      antigen was visualised on paraffin sections using DAKO Rabbit Anti-Human Ki-67
      antigen. The Ki-67LI was calculated as the percentage of Ki-67 labelled cells.
      The tumours showed variability in the Ki-67LI values. Significantly higher mean
      Ki-67LI was found for highly malignant (AIII & AIV) than for low grade gliomas
      (Al & All). For metastatic tumours, the mean values of Ki-67LI were significantly
      higher than for gliomas. Moreover, Ki-67LI of metastatic tumours were
      significantly higher than for high grade gliomas.

PMID- 11534781
TI  - Endothelial cells and angiogenesis intensity in lung cancer.
AB  - We focused our studies on single endothelial cells (ECs) scattered in
      extracellular matrix in lung cancer tumors. Neovascularization was evaluated in
      100 tumors obtained from patients operated for lung cancer, in relation to
      histological type, tumor differentiation and clinical stage of the disease.
      Angiogenic objects (single endothelial cells and microvessels) were identified by
      immunohistochemistry using monoclonal antibodies against von Willebrand factor.
      The count of angiogenic objects per 1 mm2 in each section was determined in a
      "hot spot" located at the margin of the tumor. We used an arbitrary scale of
      angiogenesis intensity: 1 - 0-200, 2 - 201-400, 3 - >400 angiogenic objects/mm2.
      A majority (57%) of the examined cases belonged to the group 2. The angiogenesis
      intensity measured by the single EC numbers/mm2 correlates with the histological
      type and the differentiation of the tumors. There was no such a correlation when
      the angiogenesis intensity was measured by counting total angiogenic objects
      (microvessels + EC) number/mm2. Single EC number/mm2 in different histological
      types of cancer were as follows: 162+/-121 in squamous cell (SqCC), 194+/-71 in
      adenocarcinoma (AdC), 225+/-145 in large cell (LCC), 264+/-52 in small cell
      (SCC), 279+/-173 in combined cancer. The differences between the EC counts in the
      different histological types of lung cancers were statistically significant in
      the following pairs: SqCC vs SCC (p=0.0233) and AdC vs SCC (p=0.0409). The
      correlation between EC count in the "hot spot" and the grade of tumor
      differentiation was statistically significant for G1 vs G4 (p=0.0007) and G1 vs
      G2 (p=0.0411). Our results suggest that higher numbers of EC/mm2 may confirm
      rapid development of angioneogenesis. These relations should be examined in
      larger series of cases.

PMID- 11534783
TI  - Localization of alpha-tubulin in the rat cumulus oophorus before and during
      preovulatory expansion.
AB  - Distribution of alpha-tubulin was investigated in the cumulus oophorus complexes
      (COCs) of the rat using anti-alpha-tubulin monoclonal antibody and fluorescence
      microscopy. Localization of alpha-tubulin was assessed in the compact and fully
      expanded COCs isolated directly from the preovulatory follicles and in the
      cryosections containing these structures. In the cryosections containing COCs,
      the submembranous distribution of alpha-tubulin marked the characteristic cell
      shapes and showed the lack of cell projections. In the freshly isolated COCs
      three-dimensional cellular arrangement was visible showing that the dispersed
      cells formed almost no projections and were not interconnected. The use of a
      higher magnification revealed a dense microtubular network radiating from
      centrosomes and extending to the plasma membrane. This network showed
      discontinuous distribution of submembranous alpha-tubulin in some of these cells.
      The latter change could be attributed to the increased progesterone production.

PMID- 11534784
TI  - Influence of active immunization against GnRH on VIP- and NPY-positive
      innervation of the porcine testis.
AB  - The influence of an anti-GnRH vaccine on VIP- and NPY-positive innervation of
      testes was studied in the pig. The immunization prevented the occurrence of
      changes in the pattern of VIP- and NPY-positive testicular innervation associated
      with the sexual maturation: it maintained the density of innervation at the high
      level characteristic for sexually immature animals. The effect was dependent on
      the method of immunization: the application of two doses of the vaccine was more
      efficient than application of only one dose, and vaccination with adjuvant was
      more efficient than vaccination with the plain vaccine. The studies on VIP and
      NPY concentration in the testicular tissue with radioimmunoassay (RIA) revealed
      immunization-dependent changes in the peptide concentration, however, some
      discrepancies between morphological changes and peptide levels were observed.

PMID- 11534785
TI  - Alterations in kidney morphology in mice with mosaic mutation.
AB  - The mosaic (Atp7a(mo-ms)) is an X-linked, lethal mutation in mice. Hemizygous
      males die at the age of 15 days and they exhibit strong similarities to the
      brindled and macular mutants. Injection of cupric chloride to mossaic mutants
      prolongs their life and diminishes the pathological results of mutation.
      Histochemical analysis of the kidneys from 14-day-old mutant males showed
      accumulation of copper in the renal cortex of the investigated animals leading to
      damage of the kidney architecture. A histological profile of the kidneys was
      defined for four groups of 14-day-old animals: mosaic males ms/-, control males
      +/-, mosaic males injected with cupric chloride ms/- (Cu), and control males
      injected with cupric chloride +/- (Cu). Pathological changes were observed in the
      cortex and in the medulla of the kidneys in both groups of mutants and control
      males injected with cupric chloride (50 microg of CuCl2 per each individual).

PMID- 11534786
TI  - Utilization of yolk platelets during early embryonic development of Rana
      temporaria and Bufo bufo.
AB  - Utilization of yolk platelets in cleaving embryos of Rana temporaria and Bufo
      bufo was studied by different methods. Morphological observations of yolk
      platelets of R. temporaria embryos at tail bud stage by transmission electron
      microscopy indicated four initial phases of platelet degradation. The pattern of
      these events is similar to that found in embryos of B. bufo. The morphological
      observations were confirmed by energy-dispersive X-ray microanalysis of the
      elemental content of platelets and by selected-area electron diffraction of
      platelet cores. Covalently bound sulphur content decreased during cleavage and
      the content of different inorganic ions changed, whereas the structure of
      crystalline core remained constant. Morphological changes found in the amorphous
      cortex of yolk platelets were due to their utilization. Stereological
      measurements indicated that utilization during cleavage increased, but only the
      initial phases of yolk platelet degradation were seen. The volume of the cortex
      did not decrease and the crystalline core did not fragment.

PMID- 11534787
TI  - Aerobic power and muscle strength among young and elderly workers with and
      without physically demanding work tasks.
AB  - The aim of the study was to investigate the effect of waste collection on the
      physical capacity of the workers. A total of 19 young and 28 elderly male waste
      collectors and two age-matched control groups participated. The aerobic power was
      estimated. The maximal isometric muscle strength was measured for back extension
      and flexion, shoulder elevation and abduction, and handgrip. The aerobic power
      was lower among the elderly workers compared with the young workers of both
      groups. No differences were found between waste collectors and control groups. A
      general tendency to larger muscle strength was found for both young and elderly
      waste collectors compared with the control groups. Waste collectors generally
      have a higher physical capacity than the control groups which is an indication of
      an early selection of the young waste collectors. With respect to the elderly
      waste collectors, the job seems to have a training effect especially for the
      shoulder muscles. No training effect is found for the aerobic power, and a
      discrepancy between work demand and individual aerobic capacity may occur among
      elderly workers resulting in a negative health effect unless the work task is
      evaluated according to age dependent criteria.

PMID- 11534788
TI  - Workplace assessment: a tool for occupational health and safety management in
      small firms?
AB  - This paper discusses the capability of small firms to comply with legislative
      demands on risk assessment. The results of a national survey show that only a
      minor fraction of small firms comply. Two case studies demonstrate that small
      firms are able to meet the demands. An analysis of these cases leads to some
      hypotheses on the preconditions for compliance. Many firms need a person to
      mediate legislative demands. The demands for qualifications to fulfil this role
      are discussed. The conclusion is that it is possible to qualify persons as
      mediators. Therefore, to stimulate ergonomic activities in small firms resources
      for such mediators are required. The occupational health services are able to
      train a staff to undertake the task.

PMID- 11534789
TI  - Passive versus active operator work in automated process control--a job design
      case study in a control centre.
AB  - Methods of avoiding common problems associated with operator work in automated
      process control, such as understimulation and difficulties in achieving and
      maintaining necessary skills and competence, are addressed in this paper. The
      source of these problems is deduced here to be that monitoring tasks are a
      predominant part of the job. This case study shows how work in a highly automated
      process can be designed not only to avoid the traditional problems, but also
      provide a stimulating job within a good work situation at the same time as
      fulfilling efficiency demands. A new definition of active/passive operator jobs
      is made which is based on a categorisation of the types of work tasks that make
      up the job. The definition gives an explanation of how different designs of
      operator jobs result in more or less active/passive work situations.

PMID- 11534790
TI  - Impact of a joint labor-management ergonomics program on upper extremity
      musculoskeletal symptoms among garment workers.
AB  - This study evaluated the effect of an ergonomics intervention program on the
      prevalence and intensity of symptoms of upper extremity work-related
      musculoskeletal disorders among 36 garment workers performing an operation called
      spooling. Adjustable chairs were introduced and workers were trained in their
      use. Symptom surveys were administered prior to and 6 months after introduction
      of adjustable chairs. Quantitative pre- and post-intervention measurement of
      joint position was performed utilizing videotapes among a subgroup of nineteen.
      Eighty nine percent of the cohort reported pain in either the neck or at least
      one upper extremity anatomic site prior to the adjustable chair intervention.
      Among subjects reporting pain at baseline, there were significantly decreased
      pain levels in 10 of 11 anatomic sites after the intervention. Among all
      subjects, the proportion reporting pain decreased for each anatomic site
      following the intervention, with statistically significant decreases in 3 sites.
      However, there were only modest declines in awkward posture among the videotaped
      subgroup. This study suggests that introduction of an ergonomics program focused
      on education and introduction of an adjustable chair may diminish musculoskeletal
      symptomatology in apparel manufacturing workers.

PMID- 11534791
TI  - Marker-less systems for tracking working postures--results from two experiments.
AB  - Two experiments are performed to examine the usability of different marker-less
      approaches in image analysis and computer vision for automatic registration of
      OWAS (Ovako working posture analysing system) postures from video film. In
      experiment 1, a parametric method based on image analysis routines is developed
      both for separating the subject from its background and for relating the shapes
      of the extracted subject to OWAS postures. All 12 analysed images were correctly
      classified by the method. In experiment 2 a computer neural network is taught to
      relate postures of a subject to OWAS postures. When the network was trained with
      53 images the rest of the set of 138 images was correctly classified. The
      experiments described in this paper show promising results regarding the use of
      image analysis and computer vision for tracking and assessing working postures.
      However, further research is needed including tests of different human models,
      neural networks, and template matching for making the OWAS method more useful in
      identifying and evaluating potentially harmful working postures.

PMID- 11534792
TI  - Effect of visual display terminal height on the trapezius muscle hardness:
      quantitative evaluation by a newly developed muscle hardness meter.
AB  - The aim of this study was to determine trapezius muscle hardness in 9 healthy
      volunteers before and after word processing tasks with a video display terminal
      (VDT) at three different heights. When using a desktop personal computer (PC), no
      change was observed in muscle hardness even after a 30-min task if a subject was
      in the reference posture with a declination angle formed by the Reid's line
      directed toward the upper edge of the PC screen and the horizontal plane within 5
      10 degrees. However, an increase in muscle hardness was observed after a 15-min
      task in a posture of looking up at the screen (angle of elevation: 15-20 degrees)
      and after a 30-min task in a posture of looking down at the screen (angle of
      declination: 15-20 degrees). When the same tasks were performed with a notebook
      PC, muscle hardness increased after 15 min. Fifteen minutes of relaxation
      exercise reduced the muscle hardness caused by VDT work.

PMID- 11534793
TI  - Evaluation of physiological work demands and low back neuromuscular fatigue on
      nurses working in geriatric wards.
AB  - This study evaluated the physiological demands and low back neuromuscular fatigue
      patterns following a daytime work shift of 21 female nurses working in geriatric
      wards. Subjects' heart rate (HR) at work was monitored for 8 h and surface
      electromyogram (EMG) of their back muscle was recorded during a 1-minute
      horizontal trunk holding test before and after work. Results showed that the
      nurses had heart rates exceeding 90 beats/min in 57% and 110 beats/min in 19% of
      their working hours. The EMG revealed a significant drop in initial median
      frequency (MF) (p = 0.04) and increase in negative slope of the MF/time plot
      (p<0.001) of the back muscle after work. These suggest that the muscles were
      fatigued after work. The nurses rated patient lifting, transfer and turning as
      most physically demanding, and these corresponded to the highest heart rates
      recorded. The physiological and neuromuscular strain on the nurses indicated that
      extreme care should be exercised at work, particularly towards the end of a work
      shift when the muscles have become fatigued.

PMID- 11534794
TI  - Polarized task lighting to reduce reflective glare in open-plan office cubicles.
AB  - This ergonomic study deals with the common situation where a glossy document is
      placed between a viewer and an under-shelf task light source in a common open
      plan office cubicle workstation. With a task lamp in front, when looking at a
      document a viewer sees two images, the document itself and specular glare, which
      is the reflected image of the light source. Specular glare or veiling reflection
      causes eye discomfort, makes it difficult to read a document and has been thought
      to contribute to eyestrain. This paper analyzes the application of polarized
      lighting for this specific situation. The use of a linear polarized light source
      helps to minimize specular glare by darkening the reflected image of the light
      source on the document. The performance and predictive optimization of the use of
      polarized lighting in this situation is investigated according to female and male
      viewer height demographics. Theoretical predictions and light measurement
      analysis of specular glare reduction are compared with empirical results from
      testing on a panel of humans on semi-gloss finish and matte finish papers. This
      study shows that with the right alteration of a polarized light source position,
      specular glare may be significantly reduced, and correlations exist between the
      theory, empirical measurements and the human response to specular glare
      reduction.

PMID- 11534795
TI  - Endurance, pain and resumption in fully flexed postures.
AB  - In this study effects of low loads in fully flexed postures were investigated.
      Thirteen men who were unused to the postures participated. Thirteen professional
      construction workers with long experience of suchlike postures were also studied.
      Pain reactions during and after loading were observed, as well as endurance time
      and the recovery process, here by studying the resumption time. Endurance and
      resumption times differed little from those given by models used for more common
      postures. Pain from the legs and not from the back limited the working ability in
      86% of the endurance tests. Thirdly, the construction workers had significantly
      longer endurance time and shorter resumption time.

PMID- 11534796
TI  - Evaluation of methods to assess push/pull forces in a construction task.
AB  - The objective of the present study was to determine the validity of methods to
      assess push/pull forces exerted in a construction task. Forces assessed using a
      hand-held digital force gauge were compared to those obtained using a highly
      accurate measuring frame. No significant differences were found between the
      methods, except for peak push forces, for which the forces assessed with the
      force gauge were significantly lower than those assessed with the measuring
      frame. When the construction task was reproduced close to the actual workplace by
      simulation against a fixed object using the force gauge, all exerted forces on
      the force gauge were significantly lower than those on the measuring frame,
      except for mean pull forces. When self-reports were compared to the exerted
      forces on the measuring frame, the construction workers overestimated the exerted
      push/pull forces by 50%. In conclusion, when applied for direct measurements, the
      force gauge can be used to validly assess push/pull forces at the workplace.

PMID- 11534797
TI  - Assessment of work postures and movements using a video-based observation method
      and direct technical measurements.
AB  - The aim was to study postures and movements during repetitive work using video
      based observations and direct technical measurements (inclinometers and
      goniometers). A total of 21 healthy women from a poultry processing plant
      volunteered. Neck flexion > 20 degrees was registered during 92% of the recorded
      time with the observation method, while the corresponding value measured with the
      inclinometer was 65%. Different reference positions and different measured
      variables apparently contributed to the differences between the methods. Mean
      wrist position was measured to be 0 degrees in flexion-extension and 19 degrees
      in ulnar deviation. Differences between the methods in the registered hand
      positions were small. The number of repetitive movements/minute and mean power
      frequency (MPF) of the electrogoniometer data was significantly related, showing
      both variables to be relevant measures of repetitiveness. In conclusion, the
      observation method and the technical measurements supplemented each other well. A
      reduction in class categories was suggested for future observation methods.

PMID- 11534798
TI  - Towards successful physical stress reducing products: an evaluation of seven
      cases.
AB  - Lifting, carrying, pushing and pulling at work are assumed to be related to
      increased risks of musculoskeletal injury, mainly in the low back and shoulder
      region. The implementation of products to reduce the physical load in heavy work
      is a well-known strategy to attack this problem. The success of these products
      depends not only on the product itself, but also on the process of product
      development and implementation. In this paper, seven cases are described where
      products have been developed to reduce the physical load on scaffolders,
      bricklayers, bricklayer's assistants, roofworkers, aircraft loaders, glaziers and
      assembly line workers. These products are described with special reference to the
      physical load problem in the occupational task, the process of product
      development, the nature of the product, the potential effects on physical load
      and the opinion of workers. From these cases, a list of key factors in product
      development contributing to the success of a product is composed. These concern
      among others a direct participation of workers, a wide analysis of risks, an
      analysis of potential negative side effects, and a systematic stepwise approach.

PMID- 11534799
TI  - Hepatic encephalopathy in rats with thioacetamide-induced fulminant hepatic
      failure: role of endotoxin and tumor necrosis factor-alpha.
AB  - BACKGROUND: Hepatic encephalopathy, a complex neuropsychiatric syndrome secondary
      to acute liver failure, chronic parenchymal liver disease or portal-systemic
      shunting, may possibly develop through mediators of endotoxin and tumor necrosis
      factor-alpha (TNF-alpha). However, there are no published data concerning the
      relationships between the severity of encephalopathy and the plasma levels of
      endotoxin and TNF-alpha. METHODS: Male Sprague-Dawley rats weighing about 300-350
      g were used. Fulminant hepatic failure was induced by intraperitoneal injection
      ofthioacetamide (350 mg/kg/day) for 3 consecutive days. Severity of
      encephalopathy was assessed by measuring motor counts using an Opto-Varimex
      animal activity meter. Plasma levels of endotoxin and TNF-alpha were determined
      by chromogenic Limulus assay and ELISA method, respectively. RESULTS: Our study
      revealed that higher plasma levels of endotoxin (> 5.9 pg/ml) and TNF-alpha (>
      18.8 pg/ml) were significantly associated with more blunted motor activities in
      rats with fulminant hepatic failure (p < 0.05). A significant correlation was
      observed between plasma concentrations of endotoxin and TNF-alpha (r = 0.59, p <
      0.001). Plasma levels of endotoxin were weakly correlated with the total
      movements in an open field (r = -0.34, p = 0.032) and the counts of ambulatory (r
      = -0.38, p = 0.014) and vertical movements (r = -0.40, p = 0.010). There were no
      correlations between the motor counts and plasma levels of TNF-alpha (p > 0.05).
      CONCLUSIONS: In addition to endotoxin and TNF-alpha, other factors may
      participate in the pathogenesis of hepatic encephalopathy in rats with
      thioacetamide-induced fulminant hepatic failure.

PMID- 11534800
TI  - Cathepsin E and subtypes of intestinal metaplasia in carcinogenesis of the human
      stomach.
AB  - BACKGROUND: Cathepsin E is found mainly over the gastric surface and foveolar
      epithelial cells, and it also is found in the metaplastic pyloric glands and
      cancer cells. The exact function of cathepsin E in gastric mucosa remains
      unclear. The colonic type (type III) of intestinal metaplasia (IM) is strongly
      associated with intestinal-type gastric carcinoma. IM is considered to be a
      precancerous lesion. The aim of this study was to find out the role of cathepsin
      E in IM, dysplasia and cancer of stomach. METHODS: Sixty nine biopsy specimens
      with IM and dysplasia and 33 gastrectomy specimens with gastric carcinoma were
      fixed, sectioned and stained with PAS-alcian blue stain, high iron-diamine alcian
      blue stain to classify IM and immunohistochemical stain to localize cathepsin E.
      Those patients with dysplastic gastric lesions received regular endoscopic follow
      up. RESULTS: Fifteen of 69 patients with gastric dysplasia developed cancer in a
      median 10.5 months follow-up. Severe dysplasia developed carcinoma significantly
      higher than mild dysplasia (12/20 vs. 1/25, p < 0.001), and type III intestinal
      metaplasia seemed to have significantly predilection for severe dysplasia and
      gastric cancer. Cathepsin E was stained in intestinal metaplasia with dysplastic
      change in 44/69 specimens (63.8%), and carcinoma in 28/48 (58.3%) specimens,
      there was no significant difference between intestinal type and diffuse type
      carcinoma in cathepsin E staining. The positive staining for cathepsin E
      decreased significantly in severe dysplastic gastric mucosa. CONCLUSIONS: Type
      III IM is commonly associated with severe dysplasia and cancer; it may be a
      precancerous lesion. The positive staining of cathepsin E decreased with the
      severity of gastric dysplasia, representing dedifferentiation of the cells.

PMID- 11534801
TI  - Follow-up of Helicobacter pylori status by using 13C-urea breath test in nonulcer
      dyspeptic patients after eradication therapy.
AB  - BACKGROUND: The role of eradication therapy is still controversial in H. pylori
      related nonulcer dyspepsia (NUD). The aim of this study was to follow up the H.
      pylori status after eradication therapy in patients with NUD by using l3C-urea
      breath test (UBT). METHODS: Patients with a clinical and endoscopic diagnosis of
      NUD were included. H. pylori infection was established by endoscopic biopsies and
      13C-UBT. Patients with H. pylori infection then received a quadruple therapy with
      colloidal bismuth subcitrate, metronidazole, tetracycline and lansoprazole. Two
      months after completion of therapy, endoscopic biopsies and 13C-UBT were
      performed again to confirm eradication. A follow-up 13C-UBT was carried out again
      in one year to detect recurrence of H. pylori infection. RESULTS: Eighty-eight of
      the 148 patients (59.5%) were found to have H. pylori infection by both
      endoscopic biopsies and 13C-UBT. Anti-H. pylori therapy was given for 55 patients
      and proved successful in 33 of them two months after the end of therapy. However,
      recurrence was found one year later in three of these 33 cases, making a
      recurrence rate of 9.1% (3/33). Three of the 22 cases with unsuccessful
      eradication were found to have H. pylori eradication at one year by follow-up 13C
      UBT. One of the 33 H. pylori-positive patients without anti-H. pylori therapy,
      who had negative 13C-UBT in one year follow-up, was found taking a high dose and
      long period of antibiotics. CONCLUSIONS: The recurrence rate of H. pylori
      infection in our study was higher than that in the Western population. Delayed
      eradication of H. pylori may occur after anti-H. pylori therapy. Spontaneous
      eradication is rare in patients not receiving anti-H. pylori eradication.

PMID- 11534803
TI  - The study of levels of norepinephrine and dopamine-beta-hydroxylase in patients
      with pregnancy-induced hypertension.
AB  - BACKGROUND: The present work aimed to study the changes of both norepinephrine
      (NE) and dopamine-beta-hydroxylase (DbetaH) in pregnancy-induced hypertension
      (PIH). METHODS: NE levels and DbetaH activity in blood were determined in 116
      patients with pregnancy-induced hypertension and 40 normal control subjects using
      high performance liquid chromatography (HPLC) and ultraviolet (UV)
      spectrophotometry. Among patients with PIH, 28 were graded as mild, 34 moderate
      and 54 severe. The normal control subjects were selected from patients at a
      normal term pregnancy receiving elective cesarean section. RESULTS: NE levels and
      DbetaH activity in blood were significantly higher in patients with severe PIH
      than those in control subjects (p < 0.05 for both). Both patients and control
      subjects had higher NE levels and DbetaH activity in the umbilical artery blood
      than in the umbilical vein blood (p < 0.05). NE levels and DbetaH activity in
      both umbilical artery and vein blood were higher in the moderate and severe PIH
      groups than in the mild (p < 0.05) and control (p < 0.05) groups. NE levels in
      the umbilical artery blood were five times higher than those in the maternal
      blood, and DbetaH activity was three times higher. NE levels and DbetaH activity
      in the umbilical artery blood were significantly higher in the PIH group with
      complicated intrauterine growth retardation (IUGR) or fetal distress than in the
      PIH group without such complication. CONCLUSIONS: The pathogenesis of PIH may
      relate to increase of excitability of the sympathetic nervous system in fetus.

PMID- 11534802
TI  - Significance of cardiac troponin I and creatine kinase release after coronary
      intervention.
AB  - BACKGROUND: Cardiac troponin I is a highly sensitive and specific marker for
      early detection of myocardial injury. Whether it can be used to monitor
      myocardial injury after coronary intervention is uncertain. This study was
      designed to measure the cardiac troponin I and creatine kinase (CK) after
      coronary intervention and investigate their clinical significance. METHODS: We
      measured cardiac troponin I and CK levels before intervention and 4 hours, 8
      hours, 12 hours and 24 hours after apparently successful coronary intervention in
      106 eligible patients. Nine patients were excluded due to missing data. We also
      followed up the clinical outcome to record major cardiac events (MACE). RESULTS:
      The frequency of cardiac troponin I increase after coronary intervention was
      higher than that of CK increase (40.2% vs 8.2%). The frequency of cardiac
      troponin I increase in the stent group was significantly higher than that in the
      PTCA group (49.2% vs 21.9%, p < 0.001). The frequency of cardiac troponin I
      increase was also higher than that of CK increase in patients with in-hospital
      events (58.8% vs 14.7%). CONCLUSIONS: Cardiac troponin I is more sensitive than
      creatine kinase in detecting myocardial injury after coronary intervention. The
      incidence of cardiac troponin I increase is significantly higher in patients
      undergoing stenting than in patients treated with balloon angioplasty only. The
      cardiac troponin I increase is more highly correlated with in-hospital events
      than is creatine kinase.

PMID- 11534804
TI  - In vitro cellular response of retinoic acid treated human oral cancer cell lines.
AB  - BACKGROUND: The purpose of this study is to identify the cellular response
      ofretinoic acid-treated human oral cancer cell lines. METHODS: Seven human oral
      cancer cell lines KB, SCC4, SCC9, SCC15, SCC25, OEC-M1, OC1 and OC2 were used for
      cell culture experiments. Direct cell number counting method was utilized to
      evaluate cellular response of these human oral cancer cells at the presence or
      absence of all-trans RA at 1 mM. RESULTS: Through 7-day observation, the cell
      population of SCC9, SCC15 and SCC25 of RA-treated groups decreased when compared
      with the non RA-treated groups. These three cell lines were further verified
      using [3H] thymidine incorporation DNA synthesis assay. KB, SCC4, OC1, OC2 and
      OEC-M1 cell lines did not show growth inhibition at the presence of RA at 1 mM.
      CONCLUSIONS: The molecular event of how SCC9, SCC15 and SCC25 are inhibited by RA
      and how KB, OC1, OC2 and OECM1 are resistant to RA can be further explored on the
      basis of this study.

PMID- 11534805
TI  - Magnetic resonance imaging appearance of intradural spinal lipoma.
AB  - Intradural spinal lipoma not associated with spinal dysraphism is a rare tumor
      often presenting with nonspecific symptoms and indolent clinical course. Its
      intradural location and fat component is the key for proper preoperative
      diagnosis, which could hardly be made by traditional imaging studies including
      plain film and myelography. Both CT and MRI can reveal the fat component of the
      tumor, but MRI is superior to CT in demonstrating its relationship with adjacent
      normal nerve tissue. We report a 32-year-old man who had back pain for years and
      the symptom progressed rapidly in recent two months. MRI revealed an intradural
      tumor at T12 level with high signal intensity on both T1- and T2-weighted images.
      The signal intensity dropped dramatically with fat saturation technique, which
      confirmed fat as its main component. The patient received surgery and the tumor
      was proved to be an intraspinal lipoma.

PMID- 11534806
TI  - Lithopedion.
AB  - Lithopedion is a rare obstetrical outcome of an undiagnosed and untreated
      advanced abdominal pregnancy, mostly found incidentally. We present a case of
      lithopedion. In a 76 year-old female suffering from cervical neoplasm, total
      abdominal hysterectomy was performed for the lesion and the lithopedion was found
      incidentally. The patient's history was unremarkable, and laboratory tests were
      normal. The patient recalled having experienced a severe abdominal pain about 50
      years before. Her physician had felt "a benign tumor" in her pelvis at that time,
      indicating that the stone child had retained in the maternal peritoneal cavity
      for 50 years.

PMID- 11534807
TI  - Validation of three-dimensional surface characterising methods: scanning electron
      microscopy and confocal laser scanning microscopy.
AB  - Surface characteristics of enosseous titanium implants have been known to
      influence the quality of osseointegration. Parameters recommended for metrical
      analysis should be supplemented by a topographical description. In this study, Ra
      values obtained by established tactile and optical profilometric methods are
      correlated with those obtained by stereo scanning electron microscopy (SEM) and
      confocal laser scanning microscopy (CLSM). As test specimens, standardised CVD
      diamond-coated titanium alloys with different microwave coating power ranging
      from 2,000 to 3,000 W were used. A non-CVD-coated corund grit-blasted specimen
      (NC) was used as reference. After coating with a CVD, power of 2,000 W Ra ranges
      from 4.33 to 5.69 microm depending on the method used. With increasing power of
      the coating process, the amplitude of the surface roughness is significantly
      increased to 4.53 to 6.89 microm. Ra values of the same sample obtained by
      different methods are also significantly different (p = 0.001). Compared with the
      established methods of tactile and optical profilometry, SEM and CLSM offer valid
      data on the surface roughness accompanied by a topographical imaging. In future
      studies, the underlying method should be specified to interpret roughness values
      correctly, as not every method is suitable for each specimen and values obtained
      by different methods vary extremely.

PMID- 11534811
TI  - Multiphoton confocal microscopy using a femtosecond Cr:forsterite laser.
AB  - With its output wavelength covering the infrared penetrating window of most
      biological tissues at 1,200-1,250 nm, the femtosecond Cr:forsterite laser shows
      high potential to serve as an excellent excitation source for the multiphoton
      fluorescence microscope. Its high output power, short optical pulse width, high
      stability, and low dispersion in fibers make it a perfect replacement for the
      currently widely used Ti:sapphire laser. In this paper, we study the capability
      of using a femtosecond Cr:forsterite laser in multiphoton scanning microscopy. We
      have performed the multiphoton excited photoluminescence spectrum measurement on
      several commonly used bioprobes using the 1,230 nm femtosecond pulses from a
      Cr:forsterite laser. Efficient fluorescence can be easily observed in these
      bioprobes through two-photon or three-photon excitation processes. These results
      will assist in the selection of dichroic beam splitter and band pass filters in a
      multiphoton microscopic system. We have also performed the autofluorescence
      spectrum measurement from chlorophylls in live leaves of the plant Arabidopsis
      thaliana excited by 1,230 nm femtosecond pulses from the Cr:forsterite laser.
      Bright luminescence from chlorophyll, centered at 673 and 728 nm, respectively,
      can be easily observed. Taking advantage of the bright two-photon
      photoluminescence from chlorophyll, we demonstrated the two-photon scanning
      paradermal and cross-sectional images of palisade mesophyll cells in live leaves
      of Arabidopsis thaliana.

PMID- 11534813
TI  - Manipulating biological samples for environmental scanning electron microscopy
      observation.
AB  - Biological samples having different characteristics were observed by
      environmental scanning electron microscopy (ESEM). The environmental conditions
      for untreated biological samples was determined by optimizing sample temperature
      and chamber pressure. When the temperature was at 4 degrees - 6 degrees C and
      chamber pressure was 5.2-5.9 Torr, the relative humidity in the specimen chamber
      was about 85%. Under these conditions, the surface features of the sample were
      completely exposed and did not exhibit charging. The images obtained from the
      untreated samples at different ESEM conditions were also compared with fixed and
      coated samples observed under high vacuum.

PMID- 11534816
TI  - Evolution of a 6-200 Mb long-range repeat cluster in the genus Mus.
AB  - By fluorescence in situ hybridization, we mapped the location of genes associated
      with the Sp100-rs cluster, a long-range repeat cluster in chromosome 1 of the
      house mouse, Mus musculus. The cluster comprises between 60 and 2000 repeats and
      extends over 6-200 Mb of the M. musculus genome, depending on the source of the
      cluster. The cluster evolved during the last two million years in the genus Mus
      in the lineage to which M. musculus belongs. The Asiatic mouse species M. caroli
      is not in this lineage and does not possess the cluster. M. caroli represents the
      ancestral genomic organization of the cluster source components Sp100, Csprs and
      Ifi75: they are located close to each other in the same chromosome band (1D).
      However, Sp100-rs, the principal gene of the cluster, is not present in the M.
      caroli genome. It is a chimeric M. musculus gene that arose by fusion of Csprs
      and the 5' part of Sp100. Sp100-rs and Ifi75 are homogeneously distributed
      throughout the cluster while Sp100 and Csprs in its original sequence context
      flank the cluster on opposite sides. Our results suggest a model for the origin
      and evolution of the long-range repeat cluster by duplication, gene fusion and
      amplification.

PMID- 11534817
TI  - Alpha-satellite DNA of primates: old and new families.
AB  - In this report we review alpha-satellite DNA (AS) sequence data to support the
      following proposed scenario of AS evolution. Centromeric regions of lower primate
      chromosomes have solely "old" AS based on type A monomeric units. Type A AS is
      efficiently homogenized throughout the whole genome and is nearly identical in
      all chromosomes. In the ancestors of great apes, a divergent variant of the type
      A monomer acquired the ability to bind CENP-B protein and expanded in the old
      arrays, mixing irregularly with type A. As a result, a new class of monomers,
      called type B, was formed. The "new" AS families were established by
      amplification of divergent segments of irregular A-B arrays and spread to many
      chromosomes before the human-chimpanzee-gorilla split. The new arrays contain
      regularly alternating monomers of types A and B. New AS is homogenized within an
      array with little or no homogenization between chromosomes. Most human
      chromosomes contain only one new array and one or a few old arrays. However, as a
      rule only new arrays are efficiently homogenized. Apparently, in evolution, after
      the establishment of the new arrays homogenization in the old arrays stopped.
      Notably, kinetochore structures marking functional centromeres are also usually
      formed on the new arrays. We propose that homogenization of AS may be limited to
      arrays participating in centromeric function.

PMID- 11534818
TI  - Nonrandom location and orientation of the inactive X chromosome in human
      neutrophil nuclei.
AB  - The nuclei of human neutrophils typically consist of a linear array of three or
      four lobes joined by DNA-containing filaments. Terminal lobes are connected to
      internal lobes via a single filament, while internal lobes have two filaments,
      each to an adjacent lobe. Some lobes also have appendages of various shapes and
      sizes. In particular, up to 17% of neutrophil nuclei of healthy women exhibit a
      drumstick-shaped appendage that contains the inactive X chromosome. This report
      provides a detailed analysis of the relationship between nuclear morphology and
      the location of the X and Y chromosomes in human neutrophils. Fluorescent in situ
      hybridization analysis revealed that the X and the Y chromosomes of male
      neutrophil nuclei are randomly distributed among nuclear lobes. Similarly, in
      female neutrophil nuclei with a drumstick appendage, the active X chromosome is
      also randomly distributed among lobes. In contrast, the inactive X chromosome is
      preferentially located in a terminal lobe in over 90% nuclei with drumsticks.
      Within the terminal lobe of nuclei with drumsticks, the inactive X chromosome
      lies distal to the point of filament attachment in 80% of the nuclei. The
      inactive X chromosome also exhibits a specific orientation within the drumstick
      appendage, with over 95% of nuclei having the X centromere located toward the tip
      of the appendage. Female nuclei without a drumstick appendage also have one of
      the X chromosomes (presumably the inactive chromosome) preferentially situated in
      a terminal lobe. Nonrandom distribution of the inactive X chromosome is discussed
      in the context of a model that considers chromosomes as determinants of
      neutrophil nuclear morphology.

PMID- 11534819
TI  - Cytogenetic analysis and construction of a BAC contig across a common
      neocentromeric region from 9p.
AB  - Over 40 cases of neocentric marker chromosomes, without detectable alpha
      satellite DNA, have been reported. Although these have originated from many
      different chromosomes, a few of these chromosomes have been involved in multiple
      cases of marker formation. In this study, two different markers originating from
      the short arm of chromosome 9 were analyzed, identifying a common neocentromeric
      region. A bacterial artificial chromosome (BAC) contig extending over more than
      900 kb has been assembled across this neocentromeric region. Fluorescent in situ
      hybridization and immunofluorescence assays (CENP-C and CENP-E) have localized
      the neocentromere to a 500 kb region. Preliminary analysis of DNA sequences in
      this neocentromere revealed a highly AT-rich region, which also has an increase
      in the level of retroviral elements compared with the average levels in the
      genome.

PMID- 11534820
TI  - The centromere composition of multiple repetitive sequences on rice chromosome 5.
AB  - The large-scale primary structure of the centromeric region of rice chromosome 5
      was analyzed, the first example in a cereal species. The yeast artificial
      chromosome (YAC) and bacterial artificial chromosome (BAC) contigs aligned on the
      centromere of rice chromosome 5 (CEN5) covered a distance of more than 670 kb.
      Strong suppression of genetic recombination, one of the features of a functional
      centromere, occurred along the contig region. The most remarkable feature of CEN5
      is the composition of the multiple repetitive elements. Oryza-specific RCS2 short
      tandem repeats were clustered along less than 100 kb at one end of the contig. At
      least 15 copies of the conserved domain of the 1.9 kb RCE1 centromeric repeats,
      which are similar to the long terminal repeats (LTRs) of gypsy-type
      retrotransposon RIRE7, were dispersed mainly in 320 kb stretches next to RCS2
      tandem clusters. Many copies of the LTR-like sequences of RIRE3 and RIRE8,
      another gypsy-type retrotransposon, were also found throughout the contig. On the
      other hand, the gagpol region was less conserved in the contig. These results
      indicate that the rice centromere is composed of multiple repetitive sequences
      with the RCS2 tandem cluster probably being situated as the core of a functional
      centromere of some hundreds of kilobases to megabases in length.

PMID- 11534821
TI  - Active role of lagging chromosomes in spindle collapse as revealed by live phase
      contrast and tubulin immunostaining in grasshopper spermatocytes.
AB  - Univalents, that is, chromosomes lacking an attached partner at the first meiotic
      division, show extremely faulty transmission. Most segregational errors stem from
      amphitelic (mitotic-like) orientation at metaphase I followed by anaphase I
      lagging. Our studies in living grasshopper spermatocytes show that amphitelic
      orientation may provoke spindle collapse: spindle elongation and cytokinesis are
      impaired and an unreduced restitution nucleus is formed. This does not prevent
      meiotic progression and eventually leads to the production of diploid gametes.
      The morphology and characteristics of spindle collapse in our material, as
      revealed by in vivo observation and tubulin immunostaining, indicate an active
      role of the chromosomes in the whole process.

PMID- 11534822
TI  - Whole arm inversions of chromosome 4 in Drosophila species.
AB  - Inversions of genetic segments during the evolution of Drosophila are well
      documented in the X chromosome and most autosomes, but little attention has been
      paid to chromosome 4, the smallest autosome or "dot chromosome" present in many
      Drosophila species. From our previous mapping we have defined probes that mark
      proximal, intermediate, and distal locations of chromosome 4 in D. melanogaster.
      In situ hybridizations on salivary gland polytene chromosomes with these probes
      show that the whole right arm, including genes within cytological region 101EF
      102F, is inverted relative to D. simulans. We also used these probes to determine
      the orientation of the arm of the dot chromosome in nine species of Drosophila,
      including eight from the melanogaster subfamily. To account for the observed
      whole arm inversions of chromosome 4 in five of the nine species examined, we
      propose that three inversion events have occurred during the evolution of these
      species. These whole arm inversions may explain some of the unusual features of
      this chromosome.

PMID- 11534823
TI  - Effect of pentagastrin on steroid secretion and proliferative activity of
      regenerating rat adrenal cortex.
AB  - The effects of three subcutaneous injections of 3 nmol/100 g body weight of the
      cholecystokinin type 2 (CCK2) receptor agonist pentagastrin on
      adrenocorticotrophic hormone (ACTH) and corticosterone secretion and
      proliferative activity of regenerating rat adrenal cortex were investigated.
      Pentagastrin did not alter either ACTH and corticosterone plasma concentrations
      or the adrenal mitotic index at day 5 of regeneration. In contrast, it increased
      (by about 50%) the adrenal mitotic index at day 8 of regeneration, and the effect
      was blocked by the simultaneous administration of equimolar doses of the CCK2
      receptor antagonist PD-135,158. It is suggested that the activation of CCK2
      receptors exerts a growth promoting action on the regenerating rat adrenal
      cortex.

PMID- 11534824
TI  - Hepatitis C virus (HCV) genotypes, human leucocyte antigen expression and
      monoclonal gammopathy prevalence during chronic HCV infection.
AB  - Patients with chronic hepatitis C virus (HCV) infection (530 in toto), and 294
      individuals with chronic liver disease of different aetiology, were enrolled in
      this study to investigate the prevalence of monoclonal gammopathies (MG) during
      chronic liver dysfunction. A monoclonal band was detected in 61 HCV+ patients and
      in nine HCV subjects only. In both instances, a correlation between MG presence
      and advanced age or degree of hepatic injury was noted. The prevalence of HCV
      genotype 2a was higher in HCV+ patients with, rather than in those without, MG.
      The MG+ HCV+ subjects did not exhibit human leukocyte antigen (HLA)-A33, B8, B65
      and DR16 expression, while an increased frequency of DR15 structure was seen in
      the same group of individuals in comparison with MG- HCV+ patients and healthy
      donors. These findings suggest a possible relationship between HLA haplotype
      expression, virus genotypes and the occurrence of MG during the course of chronic
      HCV infection.

PMID- 11534825
TI  - Gravistimulation forces the cortical microtubules to reorientate from transverse
      to random in the lower flank of actively-growing primary roots of French beans.
AB  - The gravistimulation of primary roots of seedlings of Phaseolus vulgaris for 0.5
      h did not cause any conspicuous difference in the microtubule arrays between the
      upper and the lower flanks. Exposure to gravistimulation of 1 h resulted in the
      transversely-orientated microtubules being reduced significantly in the lower
      flank of the actively elongating region, especially in the epidermis and the
      outer first and second layers of the cortex. This reduction was compensated for
      by an increase of randomly-orientated microtubules. In the region where the
      elongation rate of cells began to decrease, the microtubule arrays did not show a
      distinct difference between the two opposite flanks. When gravistimulation was
      prolonged to 2 h, the microtubule arrangement was about the same as in the
      control. The present results are not compatible with the concept that
      longitudinal microtubule arrays are induced in the lower flank under
      gravistimulation and thereby hinder the longitudinal expansion of cells in the
      lower flanks of roots.

PMID- 11534826
TI  - Chromium(VI) induced alterations in mouse spleen cells: a short-term assay.
AB  - Cr(VI), the highest oxidation state for chromium, is a carcinogenic and mutagenic
      agent. In vivo and in vitro Cr(VI) toxic effects are related to its intracellular
      fate. Once inside the cell it is reduced to stable Cr(III) by cysteine,
      glutathione and ascorbic acid. Additionally, as Cr(V) and/or Cr(IV) intermediates
      have been reported in Cr(VI) reactions with biological reductants, chromium
      damage is thought to originate from these chemical species. This work
      investigated the morphology of splenic cells after short-term exposure to Cr(VI).
      A dose of 30 mg of K2CrO4/kg body weight was administered to mice and the effects
      were studied 24 and 48 h after the injections. Histological results revealed a
      time-dependency effect of Cr(VI) on splenic cells. Changes included enlargement
      of the capsule and depletion of the red pulp cells, accompanied by an increase in
      macrophages, 24 h after injection. Partial restoration of red pulp was noted
      after 48 h.

PMID- 11534827
TI  - Nuclear non-histone protein p36 associated with colorectal tumours.
AB  - Rabbit serum raised against electrophoretically specific nuclear polypeptides
      with molecular weights of 35-40 kD from colon adenocarcinoma has been used to
      detect p36 antigen in 83.3% (40 of 48) of cases of large intestine tumours by
      means of Western blot technique. Immunological analysis revealed that this
      antiserum cross-reacted with antigen of the same molecular weight in 83.3% (10 of
      12) and 85.7% (6 of 7) nuclear protein preparations from stomach and lung
      tumours, respectively, but not in any control tissue samples. No cross-reactivity
      within the region of 36 kD was observed among nuclear proteins isolated from
      mononuclear cells of B-cell chronic lymphocytic leukaemia patients as well as
      healthy donors.

PMID- 11534829
TI  - Lipid distribution in salivary glands of larvae and adult bees (Hymenoptera:
      Apidae).
AB  - Cytochemical studies were carried out to establish lipid distribution in the
      salivary glands of larvae and adult bees, using the imidazole buffer technique.
      In the duct cells of the larval salivary gland, the reaction was positive in the
      epicuticle and negative in the glandular lumen. The absence of smooth endoplasmic
      reticulum and the presence of lipids in the intercellular space suggest that
      lipids absorbed from the haemolymph could be used in the constitution of the
      epicuticle, after having been conveyed through the epithelium. In adult workers
      (new-emerged, nurse and forager workers), the head salivary glands presented a
      positive reaction in the secretion in glandular lumen, identifying its lipidic
      nature.

PMID- 11534828
TI  - Cellular protein alterations in colorectal cancer: p28, p53 and p65 studies.
AB  - The expression and intracellular distribution of the p28 protein (MW 28 kD),
      which is electrophoretically specific for tumour cells, the p53 protein (MW 53
      kD), one of the most frequently mutated in cancer, and the oncofoetal p65 protein
      (MW 65 kD), were investigated in colorectal cancer and normal colonic mucosa. The
      correlation between the expression of these proteins and the stage of the cancer,
      was evaluated. Neoplastic and normal tissues were fractionated by differential
      centrifugation, and protein analysis was performed by means of the Western blot
      technique in the presence of polyclonal (anti-p28 and anti-p65) or monoclonal
      (anti-p53) antibodies. Among the colorectal cancer cases examined 69% (11/16),
      53% (10/19) and 77% (17/22) were positive for p28, p53 and p65, respectively.
      Immunoblot analysis revealed that the tumour specific p28 protein expression was
      mainly evident in the nuclear fraction, while the p53 and p65 proteins
      accumulated in the cell nuclei and the cytoplasm, although to different extents.
      The p65 protein appeared to be specifically expressed in the early stages of
      colorectal cancer, while a high level of p53 protein was typical for more
      invasive colorectal cancer stages.

PMID- 11534830
TI  - Action of nonviral gene delivery vectors on human complement system: low
      anticomplementary activity of lipoplexes based on lacZ plasmid and
      phospholipid/oligocation liposomes.
AB  - A simple test-system has been developed for the first time in order to detect the
      ability of effectors (lipoplexes) to activate the complement system in an
      antibody-independent manner to serve as acceptors of nascent C4b and to inhibit
      formation of the key enzyme of complement, C3-convertase. The effect of plasmid
      DNA (pCMV-SPORT-LacZ), negatively charged cardiolipin (CL), neutral
      phosphatidylcholine (PC) vesicles and their lipoplexes, on the complement system
      was studied using the method developed. It was revealed that PC vesicles did not
      affect the complement system, while CL vesicles manifested low activation. The
      influence of plasmid DNA and its lipoplex based on PC liposomes as well on the
      complement system was very low. PC/LacZ lipoplex (143 microg/ml) acted on the
      complement system like 5.36 microg/ml heat aggregated IgG (agg) (the level of no
      pathological ruptures), whereas CL/LacZ lipoplex (143 microg/ml) acted similar to
      10.7 microg/ml IgG (agg). Thus, weak activation of the complement system with CL
      lipoplex, and even weaker for the PC lipoplex testified to the use of neutral and
      positively charged lipoplexes preferably in gene therapy protocols. The technique
      can also be used for testing the influence of injectable gene therapy vectors on
      the complement system.

PMID- 11534831
TI  - The lacZ gene transfer into L929 cells and [14C]-DNA tissue distribution
      following intraperitoneal administration of new pH-sensitive lipoplexes in mice.
AB  - The efficacy of lacZ gene transfer into the L929 cell line and a local [l4C]-DNA
      delivery in male NMRI mice (10-12 weeks old), were studied using new pH-sensitive
      liposomes, containing phosphatidylcholine/glycyrrhizin (PC/GL) or alpha
      tocopherol ester of succinic acid (PC/TSA). The reporter gene (pQE-LacZ plasmid)
      was transferred into L929 cells using corresponding lipoplexes, 0.5% of cells
      being transfected. Tissue distribution of Gasserian ganglion neurinoma cell [14C]
      DNA fragments and corresponding PC/GL and PC/TSA lipoplexes, were examined
      following intraperitoneal administration of a 24 h postdose. The [14C]-DNA itself
      was not detected in any organs at a 1.5 h postdose. The use of PC/GL or PC/TSA
      lipoplexes considerably changed the biodistribution of [14C]-DNA in mice tissues.
      The maximal content of [14C]-DNA for both types of lipoplexes was observed in the
      intestine (50% dose equiv./g) and the spleen (30% dose equiv./g). The content of
      [14C]-DNA in liver and kidneys was equal to 4 and 10% for liver and kidneys in
      the case of PC/GL-lipoplexes, and 15 and 6%, for PC/TSA, respectively. Thus, the
      tropicity for PC/GL-lipoplexes to liver was not detected under i.p.
      administration.

PMID- 11534832
TI  - Effect of lamotrigine on a novel model of epilepsy.
AB  - The effect of lamotrigine (LTG) on evoked and spontaneous seizure-like activity
      induced by veratridine, was investigated. Rat brain slices were examined using
      conventional electrophysiological intracellular techniques. Alteration of sodium
      channel function by veratridine (0.3 microM) induced spontaneous seizure-like
      activity in the hippocampal CA1 pyramidal neurons. Therapeutic concentrations of
      LTG (5-10 microM) inhibited both evoked and spontaneous bursting induced by
      veratridine. This inhibition was voltage-dependent indicating possible
      interaction between the drug and the inactivated state of sodium channels. There
      was an increase in the firing threshold of the bursting but no change in the
      resting membrane potential (RMP) and membrane input resistance. Results from this
      work suggest that the veratridine model of epilepsy is very sensitive to drugs
      which act on sodium channels. These data make the veratridine model a suitable
      tool for screening potential sodium channel-dependent antiepileptic drugs.

PMID- 11534833
TI  - Hypertension in normotensive and hypertensive rats by spermine ingestion.
AB  - Polyamines (putrescine, spermidine and spermine) play an important role in the
      development of hypertension and in the expression of atrial natriuretic peptide
      (ANP), a cardiac hormone involved in the regulation of blood pressure. Wistar
      Kyoto normotensive (WKY) and spontaneously hypertensive rats (SHR) were given
      spermine in drinking water (0.5%) for 15 days. The spermine intake elevated the
      blood pressures of both SHR and WKY rats and reduced the expression of ANP
      (Northern blotting) in the ventricles. ANP levels in the plasma determined by
      enzyme immunoassay (EIA) showed no changes in the levels of plasma ANP after
      spermine intake. An analysis of polyamines by high-pressure liquid chromatography
      showed that the levels of spermine and spermidine were elevated in SHR hearts. It
      was in SHR hearts alone that spermine intake was associated with increases in the
      levels of putrescine. The results suggest that spermine-induced increases in
      blood pressure may involve mechanisms other than ANP.

PMID- 11534834
TI  - Characterization of the agarase system of a multiple carbohydrate degrading
      marine bacterium.
AB  - A marine bacterium strain 2-40 (2-40) degraded numerous complex carbohydrates,
      such as agar, chitin and alginate. It may play an important role in altering
      carbon fluxes in marine environments. End-product analyses revealed that 2-40
      synthesized an agarase system that consisted of at least three enzymes, beta
      agarase I, beta-agarase II and alpha-agarase, which acted in concert to degrade
      polymeric agar to D-galactose and 3,6-anhydro-L-galactose. The agarase system was
      shown to be both cell envelope-associated and extracellular, with the relative
      concentrations depending on the growth phase. The principal depolymerase, a beta
      agarase I, hydrolysed agar to both neoagarotetrose and neoagarobiose, as
      identified by thin layer chromatography. This agarase had a mass of 98 kD and a
      Pi of 4.3. The agarase system was repressed by D-glucose and D-galactose and
      induced by agar, agarose, neoagarobiose, neoagarotetrose and neoagarohexose.

PMID- 11534835
TI  - Dosimetry in models of child and adult for low-frequency electric field.
AB  - Induced electric field and current density in a child's body exposed to a 60-Hz
      electric field are calculated and compared with those for an adult's body.
      Because of the different proportions of the child body relative to those of the
      adult body, differences in the induced electric field and current density values
      in various organs are observed. These results are interpreted in terms of
      international guideline limits, and hypotheses regarding plausible interactions.

PMID- 11534836
TI  - Distortion of millimeter-wave absorption in biological media due to presence of
      thermocouples and other objects.
AB  - Specific absorption rate (SAR) distributions in the vicinity of a thermocouple or
      air bubble in water and in the presence of hair or sweat duct in skin were
      calculated using analytical and two-dimensional impedance methods. The objects
      were exposed to uniform 42.25 GHz plane electromagnetic fields. Insertion of a
      0.1-mm thermocouple or similarly sized air bubble into water produced a strong
      localized disturbance of the otherwise uniform SAR distribution. However, the
      average of SAR values immediately surrounding the thermocouple was close to the
      undisturbed uniform average SAR. This allows measuring the average SAR during
      exposure of both unbounded and bounded media using calibrated small thermocouples
      (up to 0.1 mm). The SAR distribution in the vicinity of a hair was qualitatively
      similar to that produced by an air bubble. The maximal value of SAR was more than
      three times higher than the overall average SAR value in the skin. Sweat ducts
      produced a smaller disturbance of the millimeter-wave (mm-wave) field.

PMID- 11534837
TI  - Electric fields in the human body resulting from 60-Hz contact currents.
AB  - Contact currents occur when a person touches conductive surfaces at different
      potentials and completes a path for current flow through the body. Such currents
      provide an additional coupling mechanism to that, due to the direct field effect
      between the human body and low-frequency external fields. The scalar potential
      finite difference method, with minor modifications, is applied to assess current
      density and electric field within excitable tissue and bone marrow due to contact
      current. An anatomically correct adult model is used, as well as a proportionally
      downsized child model. Three pathways of contact current are modeled: hand to
      opposite hand and both feet, hand to hand only, and hand to both feet. Because of
      its larger size relative to the child, the adult model has lower electric field
      and current-density values in tissues/unit of contact current. For a contact
      current of 1 mA [the occupational reference level set by the International
      Commission on Non-ionizing Protection (ICNIRP)], the current density in brain
      does not exceed the basic restriction of 10 mA/m2. The restriction is exceeded
      slightly in the spine, and by a factor of more than 2 in the heart. For a contact
      current of 0.5 mA (ICNIRP general public reference level), the basic restriction
      of 2 mA/m2 is exceeded several-fold in the spine and heart. Several microamperes
      of contact current produces tens of mV/m within the child's lower arm bone
      marrow.

PMID- 11534838
TI  - Evaluation of the cable model for electrical stimulation of unmyelinated nerve
      fibers.
AB  - The cable model, used to calculate the membrane potential of an unmyelinated
      nerve fiber due to electrical stimulation, is reexamined under passive steady
      state conditions. The validity of two of the assumptions of the cable model are
      evaluated, namely that the membrane potential be a function of the axial
      coordinate only and that the extracellular potential due to the presence of the
      nerve fiber be negligible. The membrane potential calculated from the passive
      steady-state cable model is compared with the membrane potential obtained from an
      analytical three-dimensional (3-D) volume conductor model of a nerve fiber. It is
      shown that for very small electrode-fiber distances (of only a few fiber radii),
      both assumptions are violated and the two models give quite different results.
      Over a wide range of the electrode-fiber distance (about 0.1 mm to 1 cm), both
      assumptions are fulfilled and the two models give approximately the same results.
      For very large distances (more than 10 cm, independent of fiber diameter) only
      the second assumption is satisfied, but a modification of the activating function
      of the cable model allows to calculate the membrane potential in agreement with
      the 3-D model.

PMID- 11534839
TI  - Fast and noninvasive fluorescence imaging of biological tissues in vivo using a
      flying-spot scanner.
AB  - We have developed a flying-spot scanner (FSS), for fluorescence imaging of
      tissues in vivo. The FSS is based on the principles of single-pixel illumination
      and detection via a raster scanning technique. The principal components of the
      scanner are a laser light source, a pair of horizontal and vertical scanning
      mirrors to deflect the laser light in these respective directions on the tissue
      surface, and a photo multiplier tube (PMT) detector. This paper characterizes the
      performance of the FSS for fluorescence imaging of tissues in vivo. First, a
      signal-to-noise ratio (SNR) analysis is presented. This is followed by
      characterization of the experimental SNR, linearity and spatial resolution of the
      FSS. Finally, the feasibility of tissue fluorescence imaging is demonstrated
      using an animal model. In summary, the performance of the FSS is comparable to
      that of fluorescence-imaging systems based on multipixel illumination and
      detection. The primary advantage of the FSS is the order-of-magnitude reduction
      in the cost of the light source and detector. However, the primary disadvantage
      of the FSS its significantly slower frame rate (1 Hz). In applications where high
      frame rates are not critical, the FSS will represent a low-cost alternative to
      multichannel fluorescence imaging-systems.

PMID- 11534840
TI  - Knee surgery assistance: patient model construction, motion simulation, and
      biomechanical visualization.
AB  - We present a new system that integrates computer graphics, physics-based
      modeling, and interactive visualization to assist knee study and surgical
      operation. First, we discuss generating patient-specific three-dimensional (3-D)
      knee models from patient's magnetic resonant images (MRIs). The 3-D model is
      obtained by deforming a reference model to match the MRI dataset. Second, we
      present simulating knee motion that visualizes patient-specific motion data on
      the patient-specific knee model. Third, we introduce visualizing biomechanical
      information on a patient-specific model. The focus is on visualizing contact
      area, contact forces, and menisci deformation. Traditional methods have
      difficulty in visualizing knee contact area without using invasive methods. The
      approach presented here provides an alternative of visualizing the knee contact
      area and forces without any risk to the patient. Finally, a virtual surgery can
      be performed. The constructed 3-D knee model is the basis of motion simulation,
      biomechanical visualization, and virtual surgery. Knee motion simulation
      determines the knee rotation angles as well as knee contact points. These
      parameters are used to solve the biomechanical model. Our results integrate 3-D
      construction, motion simulation, and biomechanical visualization into one system.
      Overall, the methodologies here are useful elements for future virtual medical
      systems where all the components of visualization, automated model generation,
      and surgery simulation come together.

PMID- 11534841
TI  - Computational modeling of three-dimensional microwave tomography of breast
      cancer.
AB  - Microwave tomographic approach is proposed to detect and image breast cancers.
      Taking into account the big difference in dielectrical properties between normal
      and malignant tissues, we have proposed using the microwave tomographic method to
      image a human breast. Because of the anatomical features of the objects, this
      case has to be referred to the tomography with a limited angle of observation. As
      a result of computer experiments we have established that multiview cylindrical
      configurations are able to provide microwave tomograms of the breast with a small
      size tumor inside. Using the gradient method, we have developed a computer code
      to create images of the three-dimensional objects in dielectrical properties on
      microwave frequencies.

PMID- 11534842
TI  - Variation in the dominant period during ventricular fibrillation.
AB  - Time-varying periodicities are commonly observed in biological time series. In
      this paper, we discuss three different algorithms to detect and quantify change
      in periodicity. Each technique uses a sliding window to estimate periodic
      components in short subseries of a longer recording. The three techniques we
      utilize are based on: 1) standard Fourier spectral estimation; 2) an information
      theoretic adaption of linear (autoregressive) modeling; and 3) geometric
      properties of the embedded time series. We compare the results obtained from each
      of these methods using artificial data and experimental data from swine
      ventricular fibrillation (VF). Spectral estimates have previously been applied to
      VF time series to show a time-dependent trend in the dominant frequency. We
      confirm this result by showing that the dominant period of VF, following onset,
      first decreases to a minimum and then rises to a plateau. Furthermore, our
      algorithms detect longer period correlations which may indicate the presence of
      additional periodic oscillations or more complex nonlinear structure. We show
      that in general this possibly nonlinear structure is most apparent immediately
      after the onset of VF.

PMID- 11534843
TI  - Time-varying threshold integral pulse frequency modulation.
AB  - Several methods have been proposed so far for the analysis of the integral pulse
      frequency modulation (IPFM) model and detecting its corresponding physiological
      information. Most of these methods rely on the low-pass filtering method to
      extract the modulating signal of the model. In this paper, we present an entirely
      new approach based on vector space theory. The new method is developed for a more
      comprehensive form of the IPFM model, namely the time-varying threshold integral
      pulse frequency modulation (TVTIPFM) model. The new method decomposes the driving
      signals of the TVTIPFM model into a series of orthogonal basis functions and
      constructs a matrix identity through which the input signals can be obtained by a
      parametric solution. As a particular case, we apply this method to R-R intervals
      of the SA node to discriminate between its autonomic nervous modulation and the
      stretch induced effect.

PMID- 11534844
TI  - The narcoleptic cognitive pupillary response.
AB  - It has been reported that narcoleptics exhibit deficits in short-term memory,
      list recall, and stimulus frequency estimation compared with control subjects. It
      is also well-known that pupil dilation during cognitive tasks is a measure of
      subject attention state. Here we present results from six narcoleptics and six
      controls, a total of 360 experimental records in which pupillograms were made
      during cognitive tests, which indicate that narcoleptics begin pupillary
      dilations at a smaller diameter, begin dilating earlier poststimulus, attain
      higher pupillary diameter velocities, yet achieve the same equilibrium dilation
      diameter as controls. These findings are derived from statistical tests performed
      on the parameters of a nonlinear regression model of pupillary cognitive dilation
      as a function of time. In our experiments, the standard 1-s interdigit time
      between cognitive stimuli was increased to 2.3 s, which yielded pupillographic
      time records showing that the process of short-term memory overload sets in
      gradually at about four memory digits for controls and three memory digits for
      narcoleptics. We suggest our results can be partially explained by a narcoleptic
      stimulus-encoding deficit, which limits the time available for subjects to
      rehearse cognitive tasks. However, we also report the unexpected finding that the
      inferred encoding deficit is a transient one in that repeated tasks at the same
      memory load elicit a near normal naroleptic pupillary dilation.

PMID- 11534845
TI  - Frequency domain algorithm for quantifying atrial fibrillation organization to
      increase defibrillation efficacy.
AB  - We hypothesized that frequency domain analysis of an interatrial atrial
      fibrillation (AF) electrogram would show a correlation of the variance of the
      signal and the amplitude of harmonic peaks with the periodicity and morphology
      (organization) of the AF signal and defibrillation efficacy. We sought to develop
      an algorithm that would provide a high-resolution measurement of the changes in
      the spatiotemporal organization of AF. AF was initiated with burst atrial pacing
      in ten dogs. The atrial defibrillation threshold (ADFT50) was determined, and
      defibrillation was repeated at the ADFT50. Bipolar electrograms from the shocking
      electrodes were acquired immediately preshock, digitally filtered, and a FFT was
      performed. The organization index (OI) was calculated as the ratio of the area
      under the first four harmonic peaks to the total area of the spectrum. For a 4-s
      window, the mean OI was 0.505 +/- 0.087 for successful shocks, versus 0.352 +/-
      0.068 for unsuccessful shocks (p < 0.001). Receiver operator characteristic (ROC)
      curve analysis was used to determine the optimal sampling window for predicting
      successful shocks. The area of the ROC curve was 0.8 for a 1-s window, and
      improved to 0.9 for a 4-s window. We conclude that the spectrum of an AF signal
      contains information relating to its organization, and can be used in predicting
      a successful defibrillation.

PMID- 11534847
TI  - A short-time multifractal approach for arrhythmia detection based on fuzzy neural
      network.
AB  - We have proposed the notion of short-time multifractality and used it to develop
      a novel approach for arrhythmia detection. Cardiac rhythms are characterized by
      short-time generalized dimensions (STGDs), and different kinds of arrhythmias are
      discriminated using a neural network. To advance the accuracy of classification,
      a new fuzzy Kohonen network, which overcomes the shortcomings of the classical
      algorithm, is presented. In our paper, the potential of our method for clinical
      uses and real-time detection was examined using 180 electrocardiogram records [60
      atrial fibrillation, 60 ventricular fibrillation, and 60 ventricular
      tachycardia]. The proposed algorithm has achieved high accuracy (more than 97%)
      and is computationally fast in detection.

PMID- 11534846
TI  - Perceptual time-frequency subtraction algorithm for noise reduction in hearing
      aids.
AB  - Sensorineural hearing disorders are a major and universal community health
      problem. In many cases, hearing aids offer the only solution for people suffering
      from such disorders. Unfortunately existing aids do not provide any improvement
      in intelligibility of the signal when background noise is present. A hearing aid
      system should ideally simulate auditory processes including those aspects of the
      speech signal that are perceptually important. This work presents a new
      integrated approach to the design of a digital hearing aid, based on a wavelet
      transform, as well as a formulation of the temporal and spectral psychoacoustic
      model of masking. Within the model, the Perceptual Time-Frequency Subtraction
      (PTFS) algorithm is developed to simulate the masking phenomena and reduce noise
      in single-input systems. Results show that the use of the PTFS yields a
      significant improvement in speech quality especially in unvoiced portions.
      Additionally, the noise component during periods of silence has been attenuated
      by up to 20 dB. This new noise reduction method is expected to be applicable in a
      variety of applications, including digital hearing aids and portable
      communication systems (e.g., cellular telephones).

PMID- 11534848
TI  - Miniature heart cell force transducer system implemented in MEMS technology.
AB  - A fully submersible force transducer system for use with isolated heart cells has
      been implemented using microelectromechanical systems (MEMS) technology. By using
      integrated circuit fabrication techniques to make mechanical as well as
      electrical components, the entire low-mass transducer is only a few cubic
      millimeters in size and is of higher fidelity (approximately 100 nN and 13.3 kHz
      in solution) than previously available. When chemically activated, demembranated
      single cells attached to the device contract and slightly deform a strain gauge
      whose signal is converted to an amplified electrical output. When integrated with
      a video microscope, the system is capable of optical determination of contractile
      protein striation periodicity and simultaneous measurement of heart cell forces
      in the 100-nN to 50-microN range. The average measured maximal force was Fmax =
      5.77 +/- 2.38 microN. Normalizing for the cell's cross-sectional area, Fmax/area
      was 14.7 +/- 7.7 mN/mm2. Oscillatory stiffness data at frequencies up to 1 kHz
      has also been recorded from relaxed and contracted cells. This novel MEMS force
      transducer system permits higher fidelity measurements from cardiac myocytes than
      available from standard macro-sized transducers.

PMID- 11534849
TI  - Role of nitric oxide in the stress-induced release of serotonin in the locus
      coeruleus.
AB  - Serotonergic mechanisms within the locus coeruleus (LC) are thought to be
      important in various functions including the stress response. In this study we
      investigated a possible role of nitric oxide (NO) as an intermediary messenger in
      the regulation of the serotonin (5-HT) neurotransmission within the LC. Using the
      push-pull superfusion technique coupled with HPLC and electrochemical detection,
      the in vivo release of 5-HT was determined in time periods of 10 min in the LC of
      freely moving rats. Superfusion with three different NO donors, SIN-1
      (linsidomine), S-nitroso-N-penicillamine (SNAP) or 3-(2-hydroxy-2-nitroso-1
      propylhydrazino)-1-propanamine (PAPANO) increased 5-HT release in the LC.
      Superfusion with the precursor of NO, L-arginine, for 1 h led to a sustained
      increase in 5-HT release. On the other hand, the NOS inhibitor N-methyl-L
      arginine methyl ester (L-NAME) did not significantly change the release of 5-HT.
      Infusion of N-methyl-D-aspartate (NMDA) or kainic acid, as well as exposure of
      rats to noise stress or tail pinch increased the release of 5-HT in the LC.
      Superfusion with L-NAME prevented the increase in 5-HT outflow by all these
      procedures, while the inactive isomer D-NAME had no effect. Taken together, the
      results of this study suggest that the release of 5-HT in the LC is facilitated
      by NO. Under resting conditions inhibition of NOS does not appear to
      substantially influence the release of 5-HT in the LC. However, there seems to be
      a facilitatory nitrergic influence on serotonergic responses evoked by excitatory
      amino acid receptor stimulation or various stress stimuli.

PMID- 11534850
TI  - Nisoldipine increases the bioavailability of endothelial NO.
AB  - Different observations suggest that dihydropyridine calcium antagonists alter
      endothelial NO release. Therefore, in a first step we investigated whether part
      of the nisoldipine (a dihydropyridine calcium antagonist with a possible
      selectivity for coronaries)-induced vasorelaxation was due to an NO release from
      the endothelium in porcine coronary arteries. Secondly, we directly measured
      whether nisoldipine increased NO release from rabbit aorta or the nisoldipine
      enantiomers (Bay R 1223, Bay R 1224) from rat aorta. Thirdly, we determined
      whether nisoldipine exerted antioxidative properties in segments of porcine aorta
      with intact endothelium. Blocking endothelial NO synthase with N-nitro-L-arginine
      resulted in a significant shift of the relaxation curve to higher concentrations.
      Accordingly, nisoldipine induced a concentration-dependent release of NO (direct
      electrochemical detection) from native endothelium which already started at a
      therapeutical level (1 nmol/l nisoldipine/6.5 +/- 1.2 nmol/l NO). To evaluate
      whether this effect was due to an antioxidative protection of NO, we examined the
      influence of nisoldipine on a hyperglycemia (30 mmol/l, 20 min)-induced reactive
      oxygen species release of vascular endothelium from porcine coronary arteries.
      Nisoldipine concentration-dependently reduced the reactive oxygen species release
      (>50%; 10 micromol/l). Moreover, a carbachol-induced NO release (rabbit aorta)
      which was significantly diminished by hyperglycemia was completely restored in
      the presence of nisoldipine (3 micromol/l). We conclude that nisoldipine
      increases the NO bioavailability which may result in an ameliorated endothelial
      function.

PMID- 11534851
TI  - A study of presynaptic alpha2-autoreceptors in alpha2A/D-, alpha2B- and alpha2C
      adrenoceptor-deficient mice.
AB  - The function of presynaptic alpha2-autoreceptors was studied in the hippocampus,
      occipito-parietal cortex, atria and vas deferens of NMRI mice, mice in which the
      alpha2A/D-, the alpha2B- or alpha2c-adrenoceptor gene had been disrupted
      (alpha2A/DKO, alpha2BKO and alpha2CKO, respectively), and the wildtype mice from
      which the knockout animals had been generated. Tissue pieces were preincubated
      with 3H-noradrenaline and then superfused and stimulated electrically. The alpha2
      adrenoceptor agonist medetomidine reduced the electrically evoked overflow of
      tritium in all tissues from all mouse strains (stimulation with single pulses or
      single high-frequency pulse trains, called POPs, i.e. pulse patterns leading to
      minimal autoinhibition). The effects of medetomidine did not differ in NMRI,
      wildtype, alpha2BKO and alpha2CKO mice but were greatly reduced in alpha2A/DKO
      brain preparations and to a lesser extent in alpha2A/DKO atria and vasa
      deferentia. Six drugs were tested as antagonists against medetomidine. Their pKd
      values indicated that the hippocampal and occipito-parietal alpha2-autoreceptors
      in NMRI and wildtype mice were alpha2D (the rodent variant of the alpha2A/D
      adrenoceptor) whereas the atrial and vas deferens alpha2-autoreceptors in NMRI
      and wildtype mice could not be identified with a single alpha2 subtype. Deletion
      of the alpha2A/D gene changed the pKd values in all tissues so that they now
      reflected alpha2C properties, whereas deletion of the alpha2C gene changed the
      pKd values in atria and vasa deferentia so that they now had alpha2D properties
      (as they had in NMRI and wildtype brain preparations). Autoinhibition by released
      noradrenaline was created using trains of up to 64 pulses or up to 4 POPs, and
      the overflow-enhancing effect of the alpha2 antagonist rauwolscine was
      determined. Results did not differ, irrespective of whether preparations were
      obtained from NMRI, wildtype, alpha2BKO or alpha2CKO mice: the overflow of
      tritium elicited by p pulses or POPs was much smaller than p times the overflow
      elicited by a single pulse or POP, and rauwolscine greatly increased the evoked
      overflow. Results differed, however, in tissues taken from alpha2A/DKO mice: in
      these tissues, the overflow of tritium elicited by p pulses or POPs was close to
      p times the overflow elicited by a single pulse or POP, and rauwolscine did not
      increase the evoked overflow of tritiumor increased it only marginally. When a
      greater degree of autoinhibition was produced in atria and vasa deferentia by
      stimulation with 120 pulses, both disruption of the alpha2A/D gene and disruption
      of the alpha2C gene but not disruption of the alpha2B gene attenuated the
      overflow-enhancing effects of phentolamine and rauwolscine. In NMRI and wildtype
      atria and vasa deferentia, the relative potencies of phentolamine and rauwolscine
      at enhancing the evoked overflow were not easily compatible with a single alpha2
      subtype. In alpha2A/DKO atria and vasa deferentia, the relative potencies of
      phentolamine and rauwolscine indicated that the autoinhibition-mediating
      receptors were alpha2C, whereas in alpha2CKO atria and vasa deferentia the
      relative potencies indicated that the autoinhibition-mediating receptors were
      alpha2D. It is concluded that alpha2-autoreceptors function identically in NMRI
      mice and the wildtype mice from which the receptor-deficient animals had been
      generated. There is no evidence from the experiments for any contribution of
      alpha2B-adrenoceptors to autoreceptor function. The main presynaptic alpha2
      autoreceptors are alpha2A/D, both as sites of action of exogenous agonists and as
      sites of action of previously released noradrenaline. However, there are in
      addition non-alpha2A/D-, probably alpha2C-autoreceptors. They are less prominent
      in mediating the inhibitory effects of exogenous agonists and the negative
      feedback effect of released noradrenaline. They operate not only after deletion
      of the alpha2A/D-adrenoceptors but also in normal (NMRI, wildtype) mice without
      gene deletion.

PMID- 11534852
TI  - The hyperpolarization-activated current If in ventricular myocytes of non
      transgenic and beta2-adrenoceptor overexpressing mice.
AB  - In transgenic mice (TG4) overexpressing the human beta2-adrenoceptor (beta2-AR),
      unoccupied receptors are supposed to activate spontaneously the signalling
      cascade, leading to enhanced levels of cAMP. This second messenger shifts
      activation curves of the hyperpolarization-activated current If towards less
      negative potentials. Here, we characterize If of ventricular myocytes from non
      transgenic littermate (LM) and TG4 mice and investigate whether If is modulated
      by spontaneous beta2-AR signalling. If was activated in whole-cell voltage-clamp
      experiments during test steps ranging from -65 mV to -135 mV (holding potential: 
      55 mV; 36 degrees C). In TG4 the maximum amplitude was fivefold larger than in LM
      myocytes (-1.10 +/- 0.11 pA/pF vs. -0.22 +/- 0.04 pA/pF at -135 mV), and the
      potential for half-maximum If current (VI0.5) was less negative (-100.5 +/- 1.0
      mV in TG4 vs. -108.4 +/- 2.6 mV in LM). (-)-Isoproterenol (1 microM) shifted
      VI0.5 of LM myocytes by 10.4 mV towards less negative potentials but had no
      significant effect in TG4. However, the inverse beta2-AR agonist ICI 118,551 (300
      nM) shifted VI0.5 of TG4 myocytes to values observed in LM under control
      conditions, suggesting a relation to spontaneously active beta2-ARs. Enhanced
      expression of hyperpolarization-activated and cyclic nucleotide gated channels
      (HCN) could contribute to increased maximum If amplitude in TG4 myocytes. Semi
      quantitative RT-PCR analysis demonstrated a 1.8-fold elevation of HCN4 mRNA and
      no significant change for HCN2 mRNA in TG4 ventricle. Cardiac hypertrophy was not
      detected in TG4 mice investigated here. We conclude that spontaneous beta2-AR
      signalling in hearts of TG4 mice shifts If current-voltage relation towards less
      negative potentials. Increased maximum If amplitude in TG4 myocytes is in line
      with enhanced expression of HCN channels. Both mechanisms could contribute to
      larger inward current at physiological diastolic potentials.

PMID- 11534853
TI  - Conditionally expressed G alpha 15 couples to endogenous receptors in GH3 cells.
AB  - The mammalian G proteins G15 and G16 couple a wide variety of receptors to
      phospholipase C (PLC) in co-transfected systems, and it has been suggested that
      they can be used as tools in agonist-screening systems. Using the reversed
      tetracycline-controlled transactivation system we generated rat pituitary GH3
      cell clones that expressed Galphal5 and Galpha16 conditionally to study the
      coupling of endogenous receptors to both G proteins. In cells expressing moderate
      levels of Galpha15, activation of various endogenous receptors increased inositol
      phosphate production, whereas conditional expression of Galpha16 had no
      significant effect on agonist-dependent PLC activity. Activation of PLC through
      Galpha15 in response to carbachol did not increase cytosolic [Ca2+] ([Ca2+]i) but
      stimulated protein kinase C. While carbachol decreased the secretory activity in
      non-induced GH3 cells, it increased secretion in cells expressing Galpha15. Our
      data demonstrate that Galpha15 has a higher functional promiscuity than Galpha16
      when studied in a system that preserves physiological G protein and receptor
      levels. In addition, Galpha15-mediated coupling of a receptor to PLC can change
      the cellular response to receptor agonists, indicating that downstream cellular
      functions can be used to detect receptor activation in screening systems
      employing a promiscuous G protein.

PMID- 11534855
TI  - Nitric oxide prevents inducible cyclooxygenase expression by inhibiting nuclear
      factor-kappa B and nuclear factor-interleukin-6 activation.
AB  - Stimulation of J774 macrophages with lipopolysaccharide (LPS) leads to the
      release of large amounts of prostaglandins (PGs) generated by the inducible
      isoform of cyclooxygenase (COX-2). Nitric oxide (NO), a pleiotropic free radical,
      has been demonstrated to modulate the release of a broad range of inflammatory
      mediators, amongst these PGs. In the present study we investigated the molecular
      mechanism by which NO affects cyclooxygenase pathway. Incubation of J774 cells
      with LPS caused an increase of prostaglandin E2 production and COX-2 protein
      expression which was prevented in a concentration-dependent fashion by pre
      incubating cells with sodium nitroprusside (SNP) and S-nitroso-glutathione
      (GSNO), two NO-generating agents. Electrophoretic mobility shift assay indicated
      that both NO-generating agents blocked LPS-induced activation of nuclear factor
      kappaB (NF-kappaB) by increasing IkappaB-alpha protein expression and blocking
      nuclear translocation of NF-kappaB subunits p50 and p65. SNP and GSNO also
      inhibited nuclear factor-interleukin-6 (NF-IL6) activation. These results show
      for the first time that SNP and GSNO down-regulate LPS-induced COX-2 expression
      by inhibiting NF-kappaB and NF-IL6 activation and suggest a negative feed-back
      mechanism that may be important for limiting excessive or prolonged PGs
      production in pathological events.

PMID- 11534854
TI  - Human umbilical vein: involvement of cyclooxygenase-2 pathway in bradykinin B1
      receptor-sensitized responses.
AB  - In isolated human umbilical vein (HUV), the contractile response to des-Arg9
      bradykinin (des-Arg9-BK), selective BK B1 receptor agonist, increases as a
      function of the incubation time. Here, we evaluated whether cyclooxygenase (COX)
      pathway is involved in BK B1-sensitized response obtained in 5-h incubated HUV
      rings. The effect of different concentrations of indomethacin, sodium salicylate,
      ibuprofen, meloxicam, lysine clonixinate or NS-398 administrated 30 min before
      concentration-response curves (CRC) was studied. All treatments produced a
      significant rightward shift of the CRC to des-Arg9-BK in a concentration
      dependent manner, which provides pharmacological evidence that COX pathway is
      involved in the BK B1 responses. Moreover, in this tissue, the NS-398 pKb (5.2)
      observed suggests that COX-2 pathway is the most relevant. The strong correlation
      between published pIC50 for COX-2 and the NSAIDs' pKbs estimated further supports
      the hypothesis that COX-2 metabolites are involved in BK B1 receptor-mediated
      responses. In other rings, indomethacin (30, 100 micromol/l) or NS-398 (10, 30
      micromol/l) produced a significant rightward shift of the CRC to BK, selective BK
      B2 agonist, and its pKbs were similar to the values to inhibit BK B1 receptor
      responses, suggesting that COX-2 pathway also is involved in BK B2 receptor
      responses. Western blot analysis shows that COX-1 and COX-2 isoenzymes are
      present before and after 5-h in vitro incubation and apparently COX-2 does not
      suffer additional induction.

PMID- 11534856
TI  - Reactive oxygen species potentiate the negative inotropic effect of cardiac M2
      muscarinic receptor stimulation.
AB  - The aim of the present study was to investigate the influence of reactive oxygen
      species (ROS) on the contractile responses of rat isolated left atria to
      muscarinic receptor stimulation. ROS were generated by means of electrolysis (30
      mA, 75 s) of the organ bath fluid. Twenty minutes after the electrolysis period,
      the electrically paced atria (3 Hz) were stimulated with the adenylyl cyclase
      activator forskolin (1 microM). Subsequently, cumulative acetylcholine
      concentration-response curves were constructed (0.01 nM-10 microM). In addition,
      phosphoinositide turnover and adenylyl cyclase activity under basal and
      stimulated conditions were measured. For these biochemical experiments we used
      the stable acetylcholine analogue carbachol. The atria exposed to reactive oxygen
      species were influenced more potently (pD2 control: 6.2 vs. 7.1 for electrolysis
      treated atria, P<0.05) and more effectively (Emax control: 40% vs. 90% reduction
      of the initial amplitude, P<0.05) by acetylcholine. In contrast, ROS exposure did
      not alter the responses to adenosine, whose receptor is also coupled via a Gi
      protein to adenylyl cyclase. The basal (40% vs. control, P<0.05) as well as the
      carbachol-stimulated (-85% vs. control, P<0.05) inositol-phosphate formation was
      reduced in atria exposed to ROS. The forskolin-stimulated adenylyl cyclase
      activity was identical in both groups but carbachol stimulation induced a more
      pronounced reduction in adenylyl cyclase activity in the electrolysis-treated
      atria. Accordingly we may conclude that ROS enhance the negative inotropic
      response of isolated rat atria to acetylcholine by both a reduction of the
      positive (inositide turnover) and increase of the negative (adenylyl cyclase
      inhibition) inotropic components of cardiac muscarinic receptor stimulation. This
      phenomenon is most likely M2-receptor specific, since the negative inotropic
      response to adenosine is unaltered by ROS exposure.

PMID- 11534857
TI  - Muscarinic allosteric modulation: M2/M3 subtype selectivity of gallamine is
      independent of G-protein coupling specificity.
AB  - Among the five subtypes of muscarinic acetylcholine receptors, the sensitivity
      towards allosteric modulation is generally higher in M2 and M4 receptors that
      preferentially couple to inhibitory G-proteins of the Gi/o type than in M1, M3,
      and M5 that preferentially couple to stimulatory G-proteins such as Gq/11. We
      aimed to check whether the high allosteric sensitivity of the M2 receptor
      compared to M3 is related to the differential G-protein coupling preference. As
      the third intracellular loop (i3) is known to be the major determinant in
      receptor G-protein coupling specificity, we used wild-type M2 and M3 receptors
      and the related chimeric constructs with exchanged i3-loops, i.e., M2 containing
      M3-i3 (M2/M3-i3) and M3 containing M2-i3 (M3/M2-i3). The allosteric effect of the
      archetypal modulator gallamine on the dissociation and the equilibrium binding of
      [3H]N-methylscopolamine ([3H]NMS) was measured in membranes of mouse A9L cells
      stably expressing the wild-type and the chimeric receptors (4 mM Na2HPO4, 1 mM
      KH2PO4, pH 7.4, 23 degrees C). The dissociation of [3H]NMS was monophasic under
      all conditions studied. Control values of t 1/2 were (means +/- SEM, n = 4-7):
      M2: 3.8 +/- 0.2 min, M2/M3-i3: 4.8 +/- 0.3 min, M3:43.3 +/- 4.2 min, M3/M2-i3:
      41.1 +/- 3.6 min. At M2 receptors, 0.2 microM gallamine allosterically reduced
      the apparent rate constant of dissociation k-1 to 51 +/- 5% of the control value
      (n = 5). At M2/M3-i3 the allosteric potency of gallamine was not significantly
      changed (0.2 microM gallamine --> k-1 = 61 +/- 4%, n = 7). At M3, a 20-fold
      higher concentration was required for an equieffective allosteric action (10
      microM gallamine --> k-1 = 51 +/- 5%, n = 5). The potency of gallamine at M3/M2
      i3 was not increased compared with M3 receptors (10 microM gallamine --> k-1 = 73
      +/- 2%, n = 4) but even significantly diminished. [3H]NMS equilibrium binding
      experiments revealed that neither the binding constants of gallamine at free
      receptor subtypes (pKA,M2: 7.57 +/- 0.04, n = 4; pKA,M3: 5.56 +/- 0.13, n = 3)
      nor the factors of negative cooperativity with [3H]NMS (alphaM2 = 31 +/- 1,
      alphaM3 = 3 +/- 0.4) were affected by the exchanged i3-loops (pKA,M2/M3-i3: 7.65
      +/- 0.03, pKA,M3/M2-i2: 5.35 +/- 0.24, alphaM2/M3-i3= 30 +/- 2, alphaM3/M2-i2 = 3
      +/- 0.7). In conclusion, the different sensitivities of M2 and M3 receptors
      towards allosteric modulation by gallamine are not related to the G-protein
      coupling specificity of the receptors.

PMID- 11534858
TI  - Nifedipine inhibits sphinogosine-1-phosphate-induced renovascular contraction in
      vitro and in vivo.
AB  - Sphingosine-1-phosphate (SPP) can constrict isolated intrarenal blood vessels in
      vitro and reduce renal blood flow in vivo. The present study has investigated the
      role of extracellular Ca2+ and dihydropyridine-sensitive Ca2+ channels in SPP
      induced renovascular contraction. In isolated intrarenal microvessels, cumulative
      addition of SPP (0.1-100 microM) caused concentration-dependent vasoconstriction
      (maximum effect 5.0 +/- 1.1 mN). In the presence of nifedipine (300 nM, added 30
      min before SPP) or EGTA (5 mM, added 1 min before SPP), SPP-induced
      vasoconstriction was almost completely abolished. In thiobutabarbitone
      anaesthetized rats, i.v. bolus injections of SPP (1-100 microg/kg) dose
      dependently lowered renal blood flow from basal values of approximately 4.8
      ml/min by up to 2.2 +/- 0.2 ml/min but had only little effect on mean arterial
      pressure. Pretreatment with nifedipine (10-100 microg/kg per min, i.v.) dose
      dependently attenuated SPP-induced renal blood flow reductions. We conclude that
      SPP-induced renovascular contraction requires the influx of extracellular Ca2+
      which may occur largely via nifedipine-sensitive L-type Ca2+ channels.

PMID- 11534859
TI  - Pro- and anti-inflammatory actions of ricinoleic acid: similarities and
      differences with capsaicin.
AB  - We have investigated the pro- and anti-inflammatory effects of ricinoleic acid
      (RA), the main active principle of castor oil, in an experimental model of
      blepharitis induced by intradermal injection of carrageenan in the guinea-pig
      eyelid and its possible capsaicin-like mode of action on acutely dissociated rat
      dorsal root ganglia (DRG) neurons in vitro. Topical treatment with RA (10-100
      mg/guinea-pig) or capsaicin (1-10 mg/guinea-pig) caused eyelid reddening and
      oedema. At lower doses (0.3-3 mg/guinea-pig and 0.009-0.09 mg/guinea-pig for RA
      and capsaicin, respectively) both drugs significantly potentiated the eyelid
      oedema induced by carrageenan. The tachykinin NK1 receptor antagonist FK 888
      (0.59 mg/kg s.c.) abolished the potentiation of carrageenan-induced eyelid oedema
      induced by either RA or capsaicin. The neutral endopeptidase inhibitor, thiorphan
      (1.3 mg/kg i.v.) significantly enhanced the potentiation of carrageenan-induced
      eyelid oedema produced by RA. This potentiating effect was abolished by FK 888.
      Repeated (8 days) topical application of RA (0.9 mg/guinea-pig) or capsaicin
      (0.09 mg/guinea-pig) inhibited the carrageenan-induced eyelid oedema. This anti
      inflammatory effect was accompanied by a reduction (75%-80% of SP and 46%-51% of
      NKA) in tachykinin content of the eyelids, as determined by radioimmunoassay. In
      dissociated rat DRG neurons, RA (0.1 mM for 5 min) significantly inhibited the
      inward currents induced by application of capsaicin (1 microM) and/or low pH
      (5.8), without inducing any currents by itself or changing voltage-dependent
      currents. Moreover, after 24-h incubation, RA (0.1 mM) significantly decreased
      the capsaicin (1 microM)-induced calcitonin gene-related peptide (CGRP) release
      from rat DRG neurons, whereas acute drug superfusion did not evoke CGRP release
      by itself. Summarizing, RA possesses capsaicin-like dual pro-inflammatory and
      anti-inflammatory properties which are observed upon acute and repeated
      application, respectively. However, unlike capsaicin, RA does not induce inward
      current in DRG neurons and it is devoid of algesic properties in vivo.

PMID- 11534860
TI  - C-phycocyanin protects cerebellar granule cells from low potassium/serum
      deprivation-induced apoptosis.
AB  - We tested the potential cytoprotective role of C-phycocyanin in rat cerebellar
      granule cell cultures. Cell death was induced by potassium and serum (K/S)
      withdrawal. Cell viability was studied using the neutral red assay and laser
      scanning cytometry with propidium iodide as fluorochrome. C-phycocyanin (1-3
      mg/ml) showed a neuroprotective effect against 24 h of K/S deprivation in
      cerebellar granule cells. After 4 h K/S deprivation this compound (3 mg/ml)
      inhibited formation of reactive oxygen species, measured as 2',7'
      dichlorofluorescein fluorescence, showing its scavenger capability. Pre-treatment
      with C-phycocyanin reduced thymidine incorporation into DNA below control values
      and reduced dramatically apoptotic bodies as visualized by propidium iodide,
      indicating inhibition of apoptosis induced by K/S deprivation. Flow cytometry
      studies, using propidium iodide in TritonX100 permeabilized cells, indicated that
      24 h K/S deprivation acts as a proliferative signal for cerebellar granule cells,
      which show an increase in S-phase percentage and cells progressed into the
      apoptotic pathway. C-phycocyanin protected cerebellar granule cells from the
      apoptosis induced by deprivation. These results suggest that C-phycocyanin
      prevents apoptosis in cerebellar granule cells probably through the antioxidant
      activity. It is proposed that K/S deprivation-induced apoptosis could be due, in
      part, to an alteration in the cell cycle mediated by an oxidative stress
      mechanism.

PMID- 11534861
TI  - Multichannel electroencephalographic assessment of auditory evoked response
      suppression in schizophrenia.
AB  - Reduced auditory evoked response (AER) suppression in a paired-stimulus paradigm
      (where suppression equals the difference between S1 and S2 amplitudes divided by
      S1 amplitude) may index genetic liability for schizophrenia. The present report
      is a multiple-channel electroencephalographic (EEG) study of AER suppression
      among 20 normal and 20 schizophrenia subjects. The typical paired-stimulus
      paradigm was used to evoke time-locked AERs. AER responses were scored at P50 and
      N100 in the time domain using both single (Cz) and multichannel data (after
      reduction using principal components analysis, PCA), and were scored for
      information in the gamma (20-50 Hz) and low-frequency (1-20 Hz) ranges using
      multichannel information (also after PCA). The time domain analyses demonstrated
      that schizophrenia patients differ from normal in amplitude of response to the
      first, but not to the second, stimulus for both P50 and N100. The frequency
      domain data demonstrated that schizophrenia patients differed from normal on
      amplitude of the low-frequency response (LFR) to the first, but not to the
      second, stimulus. The groups did not differ significantly on amplitudes of the
      gamma-band responses. Group separations were largest for the multichannel N100
      and LFR data, with the LFR demonstrating a modestly better risk ratio for
      differentiating schizophrenia from normal subjects. The present results suggest
      two novel differences from previous AER suppression studies: (1) S1 amplitudes
      largely determine differences between normal and schizophrenia groups on AER
      suppression, and (2) frequency domain analyses may provide important
      complimentary information when studying AERs in schizophrenia.

PMID- 11534862
TI  - Reciprocal changes of excitability between tibialis anterior and soleus during
      the sit-to-stand movement.
AB  - The excitability of spinal motoneurons is modified by central preparatory
      commands before muscle activation. In relatively complex long duration motor
      tasks such as the sit-to-stand (STS) movement, the central nervous system
      commands have to take into account the inputs from muscle, skin, and joint
      afferents during muscle contraction. We have investigated the changes occurring
      in tibialis anterior (TA) and soleus (SOL) motoneuronal excitability prior to and
      during the STS movement in normal subjects. Twelve healthy volunteers received
      the instruction to rise from a chair at the perception of an acoustic 'go'
      signal. Cortical transcranial magnetic stimuli (TMS) or peripheral nerve
      electrical stimuli (PNS) were used as test stimuli to elicit, respectively, the
      motor evoked potential (MEP) and the H reflex, at intervals of 50-1500 ms after
      the 'go' signal. Both the MEP and the H reflex were enhanced in the TA between
      100 and 900 ms after the 'go' signal. At the same time there was inhibition of
      the H reflex but not of the MEP in the SOL. At the end of the STS movement,
      during quiet standing, the size of both the H reflex and the MEP of the TA were
      not different from those obtained in the sitting position. However, in SOL, the H
      reflex was smaller, and the MEP was larger, than at rest. Our observations
      suggest the participation of several mechanisms of control of motoneuronal
      excitability during the STS, ultimately leading to a dominant role of presynaptic
      inhibitory mechanisms in SOL during standing.

PMID- 11534863
TI  - Cross-modal links in endogenous spatial attention are mediated by common external
      locations: evidence from event-related brain potentials.
AB  - Recent behavioural and event-related potential (ERP) studies reported cross-modal
      links in spatial attention between vision, audition and touch. Such links could
      reflect differences in hemispheric-activation levels associated with spatial
      attention to one side, or more abstract spatial reference-frames mediating
      selectivity across modalities. To distinguish these hypotheses, ERPs were
      recorded to lateral tactile stimuli, plus visual (experiment 1) or auditory
      stimuli (experiment 2), while participants attended to the left or right hand to
      detect infrequent tactile targets, and ignored other modalities. In separate
      blocks, hands were either in a crossed or uncrossed posture. With uncrossed
      hands, visual stimuli on the tactually attended side elicited enhanced N1 and P2
      components at occipital sites, and an enhanced negativity at midline electrodes,
      reflecting cross-modal links in spatial attention from touch to vision. Auditory
      stimuli at tactually attended locations elicited an enhanced negativity
      overlapping with the N1 component, reflecting cross-modal links from touch to
      audition. An analogous pattern of results arose for crossed hands, with tactile
      attention enhancing auditory or visual responses on the side where the attended
      hand now lay (i.e. in the opposite visual or auditory hemifield to that enhanced
      by attending the same hand when uncrossed). This suggests that cross-modal
      attentional links are not determined by hemispheric projections, but by common
      external locations. Unexpectedly, somatosensory ERPs were strongly affected by
      hand posture in both experiments, with attentional effects delayed and smaller
      for crossed hands. This may reflect the combined influence of anatomical and
      external spatial codes within the tactile modality, while cross-modal links
      depend only on the latter codes.

PMID- 11534864
TI  - The relationship between physiological tremor and the performance of rapid
      alternating movements in healthy elderly subjects.
AB  - The power distribution in the frequency spectrum of tremor is known to vary among
      individuals and its median power frequency declines with ageing. The purpose of
      the present study was to determine whether a reduction of the central component
      of physiological tremor would correlate with a reduction of motor performance.
      Then, the power distribution in the frequency spectrum of tremor from limb
      extremities might serve as an index of neural drive in healthy elderly subjects.
      Rest tremor, postural tremor from the finger, and pronation-supination at the
      wrist were recorded in 102 healthy nuns living in a convent (mean of 72+/-12
      years). Results reveal that several elderly subjects possessed a power
      distribution of tremor very similar to that of much younger subjects (mean 27
      years+/-3 SD), showing a preponderance of power within the 7.6- to 12.5-Hz band.
      Duration of pronation-supination cycles of these elderly subjects was, however,
      similar to that of other elderly subjects who had a preponderance of power within
      the 3.6- to 7.5-Hz band. Consequently, healthy elderly subjects who possessed a
      predominance of power within higher frequencies were not at an advantage over
      other healthy elderly subjects when performing a pronation-supination task. The
      age of subjects was, however, a better predictor or motor performance. In
      conclusion, the present findings suggest that, under normal physiological
      conditions, a reduction of the central component of physiological tremor does not
      induce a reduction of motor performance. Consequently, tremor recorded at limb
      extremities cannot be used as an index of neural drive.

PMID- 11534865
TI  - Highly 4-aminopyridine sensitive delayed rectifier current modulates the
      excitability of guinea pig cerebellar Purkinje cells.
AB  - The effects of low concentrations of 4-aminopyridine (4-AP) on the membrane
      properties of guinea pig cerebellar Purkinje cells were investigated in slice
      preparation using intracellular recordings. It was found that 1-10 microM 4-AP
      did not affect the resting potential or the input resistance of the cells, but
      reduced markedly the duration of the slowly depolarizing potential (SDP), and
      thus the latency to the firing of Ca2+ spikes in response to intracellular
      current pulses. Intradendritic recordings in the presence of tetrodotoxin, Cd2+,
      and low [Ca2+]o, which blocked all the regenerative responses, exhibited
      prominent membrane outward rectification in response to depolarizing current
      pulses. Under these conditions, the SDP was abolished and, in contrast, a slowly
      developing hyperpolarization was consistently observed. Application of 10 microM
      4-AP reduced the outward membrane rectification in a reversible manner, but did
      not affect the transient hyperpolarization, which is usually attributed to the
      activation of potassium "A" current. These results demonstrate, for the first
      time, the presence of a highly 4-AP sensitive delayed rectifier in guinea pig
      cerebellar Purkinje cells, which prominently affects their excitability. The
      results also indicate that the slowly depolarizing potential of guinea pig
      Purkinje cells does not involve inactivation of transient potassium currents,
      which has been suggested previously as an underlying mechanism for this
      phenomenon in turtle Purkinje cells.

PMID- 11534866
TI  - Immunohistochemical investigation of actin-anchoring proteins vinculin, talin and
      paxillin in rat brain following lesion: a moderate reaction, confined to the
      astroglia of brain tracts.
AB  - The present study investigated the immunoreactivity of vinculin, talin and
      paxillin following stab wounds in the cortex and the underlying white matter of
      adult rats. These proteins participate in the anchoring of actin filaments to the
      cell membrane at the focal adhesion plaques, and they are of essential importance
      in cell motility. Without lesion, vinculin, talin and paxillin immunopositive
      astrocytes were not recognizable in the cortex and only scarcely in the white
      matter, if at all. Following lesion, several astrocytes immunopositive to
      vinculin, talin and paxillin appeared in the white matter, whereas none of them
      was found in the overlying cortex. Glial fibrillary acidic protein (GFAP)
      immunopositivity was intense in both areas. The distribution of the actin
      anchoring proteins following lesions was similar to that found of the
      intermediate-filament associated protein plectin, in our previous study.

PMID- 11534867
TI  - The distribution of mislocalizations across fingers demonstrates training-induced
      neuroplastic changes in somatosensory cortex.
AB  - The somatosensory system has been shown to alter its cortical activation patterns
      in reaction to changes in the attended sensory input to certain body parts.
      Whether these modifications in the functional organization of the somatosensory
      cortex of humans also result in perceptual changes has rarely been investigated.
      Here we used near-threshold tactile stimuli to the center of the fingertips to
      evoke mislocalizations to fingers other than the stimulated. In healthy untrained
      subjects, the distribution of the mislocalizations from each of the fingers was
      different from a distribution expected if the subjects were purely guessing the
      position of the stimulus. The digits next to the stimulated one receive a higher
      number of mislocalizations than digits further away from the stimulated digits.
      This decrease can be accounted for by digit-overlapping receptive fields in
      combination with the sequential representation of the digits in the primary
      somatosensory cortex. In a second experiment subjects received 20 h of
      simultaneous stimulation of the left thumb and little finger in the context of a
      perceptual task. For both hands, the distribution of mislocalization from these
      fingers was analyzed at the beginning and the end of the training. For the left
      hand, the number of assigned mislocalizations to the most distant neighbor digit
      (i.e., the simultaneously stimulated digit in the training) increased while the
      number of mislocalizations toward the direct neighboring digit decreased with the
      training. This change did not occur in the untrained right hand, or in the
      untrained subjects. We conclude that the distribution of mislocalization to
      fingers other than the stimulated can be used to investigate perceptual changes
      paralleling training-induced modifications in the activation patterns of the
      somatosensory cortex.

PMID- 11534868
TI  - Modulation of the periodontally evoked masseter reflexes by mechanical
      stimulation of the face.
AB  - The current study was designed to determine if facial skin stimulation has a
      modulatory effect on the jaw reflexes that are elicited by tooth stimulation.
      This was investigated in eight human volunteers. The testing involved six
      sessions (three control and three test runs) of 50 identical tooth stimuli of 2
      N, at 400 N/s, with 0.5 N preload, to the upper left central incisor. The
      stimulus typically induced an inhibitory reflex that was immediately followed by
      an excitatory reflex. All reflexes were recorded by surface electromyogram (SEMG)
      from the ipsilateral masseter. During the control runs, the tooth stimulus was
      delivered alone while the test runs involved mechanical stimulation of the skin
      as the tooth stimulus was repeated. The mechanical skin stimulation was achieved
      by rubbing a toothbrush with approximately 5 N of force, over the area of the
      face innervated by the maxillary division of the trigeminal nerve. The effect of
      skin stimulation on the periodontally induced reflex was measured by comparing
      the control and test reflex activity. When the SEMG of the test reflex was
      subtracted from the control reflex, the difference was a net increase in the SEMG
      in all eight subjects. There was also a significant reduction in the decline of
      the bite force. It is concluded that the skin stimulation can modulate the
      reflexes that are induced by tooth stimulus. It is postulated that this
      modulation may be partly responsible for matching the size and consistency of the
      food bolus with the appropriate bite force during mastication.

PMID- 11534869
TI  - Cortical excitability is not depressed in movement-modulated stretch response of
      human thumb flexor.
AB  - There is strong evidence that the predominant pathway of the long-latency stretch
      reflex for flexor pollicis longus crosses the motor cortex. This reflex response
      is diminished during active thumb movements. We tested the hypothesis that this
      could be due to a decrease in the excitability of the transcortical component
      during movement. During isometric, concentric and eccentric thumb movements,
      transcranial magnetic stimulation (TMS) of the motor cortex was given at a time
      when the reflex signal was traversing the motor cortex. TMS was also given
      earlier in separate runs when the signal was traversing the spinal cord under
      each of the three contractile conditions. The electromyogram was analysed for non
      linear summation between stretch responses and the potential evoked by the
      cortical stimulus. The response to TMS alone was uniform across the three types
      of contraction, and the lack of cortical involvement in the short-latency reflex
      was confirmed. The TMS-evoked response summed in a non-linear manner with the
      long-latency reflex response, confirming that the excitability of the motor
      cortex was increased as the reflex signal passed through it. The long-latency
      response was markedly depressed during isotonic compared with isometric
      contractions. However, the non-linear summation was not greater during the
      isometric contractions. Thus, the depressed reflex responses during isotonic
      movements do not stem from reduced motor cortical responsiveness or afferent
      input to the transcortical pathway, and may instead reflect modulation of
      cutaneous reflexes during isotonic contractions.

PMID- 11534870
TI  - Stabilization of posture by precision touch of the index finger with rigid and
      flexible filaments.
AB  - Light touch of the index finger with a stationary surface at non-mechanically
      supportive force levels (<100 g) greatly attenuates the body sway of standing
      subjects. In three experiments, we evaluated the properties of finger contact and
      of the contacted object necessary to produce postural stabilization in subjects
      standing heel-to-toe with eyes closed, as well as how accurately hand position
      can be controlled. Experiment 1 involved finger contact with flexible filaments
      of different bending strengths, a flat surface, and an imagined spatial position.
      Contact with the flat surface was most effective in attenuating sway; the
      flexible filaments were much less effective but still significantly better than
      imagined contact. Experiment 2 compared the effectiveness of finger contact with
      a flexible filament, a rigid filament of the same diameter, a flat surface, and
      an imagined spatial position. The rigid filament and flat surface conditions were
      equally effective in attenuating body sway and were greatly superior to contact
      with the flexible filament, which was superior to imagined contact. Experiment 3
      included five conditions: arms by sides; finger "contact" with an imagined
      spatial position; finger contact with a flat surface; finger contact with a
      flexible filament attempting to maintain it bent; and contact with the flexible
      filament attempting not to bend it. The arms by sides and finger "contact" with
      an imagined position conditions did not differ significantly; all three
      conditions involving actual finger contact showed significantly less center of
      pressure and hand sway, but contact with the flat surface was most effective in
      attenuating both postural and hand displacement. In all three experiments, the
      level of force applied in fingertip contact conditions was far below that
      necessary to provide mechanical stabilization. Our findings indicate that: (1)
      stimulation of a small number of receptors in the fingertip is adequate to allow
      stabilization of sway, (2) fingertip force levels as low as 5-10 g provide some
      stabilization, (3) contact with a stationary spatial referent is most effective,
      and (4) independent control of arm and torso occurs when finger contact is
      allowed.

PMID- 11534871
TI  - Paired-pulse repetitive transcranial magnetic stimulation of the human motor
      cortex.
AB  - In nine healthy humans we modulated corticospinal excitability by using
      conditioning-test paired-pulse transcranial magnetic stimulation in a repetitive
      mode (rTMS), and we compared its effect to conventional single-pulse rTMS. We
      applied 80 single pulses or 80 paired pulses to the motor cortex at frequencies
      ranging from 0.17 to 5 Hz. The conditioning-test intervals were 2, 5, or 10 ms.
      Motor evoked potential (MEP) amplitudes from the abductor digiti minimi (ADM) as
      target muscle and extensor carpi radialis (ECR) indicated the excitability
      changes during and after rTMS. During paired-pulse rTMS at a facilitatory
      conditioning-test interval of 10 ms, we observed a facilitation of MEPs at 1, 2,
      and 5 Hz. A similar facilitation was found during single-pulse rTMS, when
      stimulus intensity was adjusted to evoke MEPs of comparable size. Using an
      inhibitory conditioning-test interval of 2 ms, paired-pulse rTMS at frequencies
      of 1 and 2 Hz caused no change in MEP size during the train. However, paired
      pulse rTMS at 5 Hz caused a strong enhancement of MEP size, indicating a loss of
      paired-pulse inhibition during the rTMS train. Since no facilitatory effect was
      observed during single-pulse rTMS with an adjusted stimulus intensity, the MEP
      enhancement during 5 Hz rTMS was specific for "inhibitory" paired-pulse rTMS.
      After 5 Hz rTMS MEPs were facilitated for 1 min, and this effect was not
      substantially different between paired-pulse rTMS and single-pulse rTMS. The
      correlation between ADM and ECR was most pronounced at 5 Hz rTMS. We conclude
      that paired-pulse rTMS is a suitable tool to study changes in corticospinal
      excitability during the course of rTMS. In addition, our data suggest that short
      trains of paired-pulse rTMS are not superior to single-pulse rTMS in inducing
      lasting inhibition or facilitation.

PMID- 11534872
TI  - Adaptive changes in smooth pursuit eye movements induced by cross-axis pursuit
      vestibular interaction training in monkeys.
AB  - The smooth pursuit system interacts with the vestibular system to maintain the
      accuracy of eye movements in space. To understand neural mechanisms of short-term
      modifications of the vestibulo-ocular reflex (VOR) induced by pursuit-vestibular
      interactions, we used a cross-axis procedure in trained monkeys. We showed
      earlier that pursuit training in the plane orthogonal to the rotation plane
      induces adaptive cross-axis VOR in complete darkness. To further study the
      properties of adaptive responses, we examined here the initial eye movements
      during tracking of a target while being rotated with a trapezoidal waveform (peak
      velocity 30 or 40 degrees/s). Subjects were head-stabilized Japanese monkeys that
      were rewarded for accurate pursuit. Whole body rotation was applied either in the
      yaw or pitch plane while presenting a target moving in-phase with the chair with
      the same trajectory but in the orthogonal plane. Eye movements induced by
      equivalent chair rotation with or without the target were examined before and
      after training. Before training, chair rotation alone resulted only in the
      collinear VOR, and smooth eye movement-tracking of orthogonal target motion
      during rotation had a normal smooth pursuit latency (ca 100 ms). With training,
      the latency of orthogonal smooth tracking eye movements shortened, and the mean
      latency after 1 h of training was 42 ms with a mean gain, at 100 ms after
      stimulus onset, of 0.4. The cross-axis VOR induced by chair rotation in complete
      darkness had identical latencies with the orthogonal smooth tracking eye
      movements, but its gains were <0.2. After cross-axis pursuit training, target
      movement alone without chair rotation induced smooth pursuit eye movements with
      latencies ca 100 ms. Pursuit training alone for 1 h using the same trajectory but
      without chair rotation did not result in any clear change in pursuit latency (ca
      100 ms) or initial eye velocity. When a new target velocity was presented during
      identical chair rotation after training, eye velocity was correspondingly
      modulated by just 80 ms after rotation onset, which was shorter than the expected
      latency of pursuit (ca 100 ms). These results indicate that adaptive changes were
      induced in the smooth pursuit system by pursuit-vestibular interaction training.
      We suggest that this training facilitates the response of pursuit-related neurons
      in the cortical smooth pursuit pathways to vestibular inputs in the orthogonal
      plane, thus enabling smooth eye movements to be executed with shorter latencies
      and larger eye velocities than in normal smooth pursuit driven only by visual
      feedback.

PMID- 11534873
TI  - Transitions in a postural task: do the recruitment and suppression of degrees of
      freedom stabilize posture?
AB  - In this study, we examined flexibility in postural coordination by inducing
      transitions between postural patterns. Previous work demonstrated that the
      postural control system produces two task-specific postural patterns as a
      function of the frequency of support surface translation. For slow translation
      frequencies (<0.5 Hz), subjects ride on the platform reminiscent of upright
      stance (ride pattern), and for fast frequencies (> or =0.75 Hz) subjects actively
      fixed the head and trunk in space (head fixed pattern) during anterior-posterior
      platform motion. To study the adaptation of the postural control system, we had
      subjects stand on a support surface undergoing increases (from 0.2 to 1.0 Hz in
      0.1-Hz steps) and decreases (from 1.0 to 0.2 Hz in 0.1-Hz steps) in translation
      frequency with the eyes open and closed. Kinematic measures of sagittal plane
      body motion revealed a gradual transition between these two postural patterns as
      a function of frequency scaling. In both the increasing and decreasing frequency
      conditions with visual input, center of mass displacements gradually decreased
      and increased, respectively, whereas upper-trunk (and head) displacement
      decreased gradually within the ride pattern until a head fixed pattern was
      observed without any significant changes in displacement for translation
      frequencies at and above 0.6 Hz. Without visual input, the scaling of the ride
      pattern was similar except the transition to the head fixed pattern never emerged
      with increasing frequency; instead, a less stable pattern exhibiting slow drift
      in head-trunk anterior-posterior motion (drift pattern) was observed at and above
      0.5 Hz oscillations. The stability of the head fixed pattern at fast frequencies
      was clearly dependent on visual input suggesting that vision was more critical
      for trunk and head control in space at high than low translation frequencies.
      Head velocity was kept constant, and lower with vision, as translation frequency
      (and velocity) changed suggesting a head velocity threshold constraint across
      postural patterns. The gradual transition from the ride to the head fixed pattern
      was made possible by the recruitment of available degrees of freedom in the form
      of ankle, then knee, and then hip joint motion. In turn, the transition from the
      head fixed or drift pattern was made possible by the gradual suppression of
      available degrees of freedom in the form of reducing hip, then knee, and then
      ankle motion. The gradual change in postural kinematics without instabilities and
      hysteresis suggests that the ability to recruit and suppress biomechanical
      degrees of freedom allows the postural control system to gradually change
      postural strategies without suffering a loss of stability. The results are
      discussed in light of possible self-organizing mechanisms in the multisensory
      control of posture.

PMID- 11534874
TI  - Effects of local and remote muscle pain on human jaw reflexes evoked by fast
      stretches at different clenching levels.
AB  - Muscle pain imposes significant changes on natural motor tasks, but the
      consequences for stretch reflexes are still disputed. The present study examined
      the jaw reflexes to fast (10 ms) stretches of the mandible in an experimental
      model with local pain in the masseter muscle and remote pain in the tibialis
      anterior muscle. The stretch reflexes were elicited in healthy volunteers (n=13)
      before, during, and after periods with constant levels of experimental pain and
      while the subjects clenched at 0%, 15%, 30%, and 45% of the maximal voluntary
      contraction (MVC) levels. Surface electromyography (EMG) was used to record the
      reflex responses. Pain in the masseter muscle (mean +/- SEM, 3.8+/-0.4 on a 10-cm
      visual analogue scale), but not in the tibialis anterior muscle (3.4+/-0.3;
      paired t-test, P=0.318) was associated with significant changes in both
      prestimulus EMG activity (ANOVA, P=0.002) and in peak-to-peak amplitudes of the
      stretch reflex (ANOVA, P=0.022). However, when the changes in prestimulus EMG
      activity were taken into consideration a significant increase in the stretch
      reflex persisted in the painful muscle at 15% and 30% MVC. Local circuits at the
      trigeminal level involving the fusimotor system are proposed to mediate a
      significant part of this modulatory effect.

PMID- 11534875
TI  - Can imaginary head tilt shorten postrotatory nystagmus?
AB  - In healthy subjects, head tilt upon cessation of a constant-velocity yaw head
      rotation shortens the duration of postrotatory nystagmus. The presumed mechanism
      for this effect is that the velocity storage of horizontal semicircular canal
      inputs is being discharged by otolith organ inputs which signal a constant yaw
      head position when the head longitudinal axis is no longer earth-vertical. In the
      present study, normal subjects were rotated head upright in the dark on a
      vertical-axis rotational chair at 60 degrees/s for 75 s and were required to
      perform a specific task as soon as the chair stopped. Horizontal position of the
      right eye was recorded with an infra-red video camera. The average eye velocity
      (AEV) was measured over a 30-s interval following chair
      acceleration/deceleration. The ratios (postrotatory AEV/perrotatory AEV) were 1.1
      (SD 0.112) when subjects (N=10) kept their head erect, 0.414 (SD 0.083) when
      subjects tilted their head forward, 1.003 (SD 0.108) when subjects imagined
      watching a TV show, 1.012 (SD 0.074) when subjects imagined looking at a painting
      on a wall, and 0.995 (SD 0.074) when subjects imagined floating in a prone
      position on a lake. Thus, while actual head tilt reduced postrotatory nystagmus,
      the imagination tasks did not have a statistically significant effect on
      postrotatory nystagmus. Therefore, velocity storage does not appear to be under
      the influence of cortical neural signals when subjects imagine that they are
      floating in a prone orientation.

PMID- 11534876
TI  - Sertraline, paroxetine, and venlafaxine in refugee posttraumatic stress disorder
      with depression symptoms.
AB  - Three new antidepressants were used in treating posttraumatic stress disorder
      (PTSD) and symptoms of depression in Bosnian refugees. Thirty-two Bosnian
      refugees seeking treatment at a mental health clinic participated in a case
      series study. All received open trials of Sertraline (n = 15), Paroxetine (n =
      12), or Venlafaxine (n = 5), with standard clinical doses. Overall, Sertraline
      and Paroxetine produced statistically significant improvement at 6 weeks in PTSD
      symptom severity in depression, and in Global Assessment of Functioning.
      Venlafaxine produced improvement in PTSD symptom severity and in Global
      Assessment of Functioning, did not yield improvement in symptoms of major
      depressive disorder; and had a high rate of side effects. Notwithstanding
      improvement of symptoms, all 32 refugees remained PTSD positive at the diagnostic
      level at the 6-week follow-up.

PMID- 11534877
TI  - Open trial of nefazodone for combat veterans with posttraumatic stress disorder.
AB  - Fourteen combat veterans completed a 9-week open trial of nefazodone for
      treatment of posttraumatic stress disorder (PTSD). Overall PTSD symptoms as
      measured by the Clinician-Administered PTSD Scale (CAPS) showed a modest but
      statistically significant decrease with nefazodone treatment. Decreases in CAPS
      reexperiencing and avoidance, but not hyperarousal symptoms, approached
      statistical significance. Anxiety decreased significantly, and there were trends
      toward decreased depression and anger on structured assessments. This study adds
      to the clinical evidence that nefazodone may be helpful for the management of
      PTSD symptoms.

PMID- 11534878
TI  - Fluvoxamine and sleep disturbances in posttraumatic stress disorder.
AB  - This study assesses the efficacy of fluvoxamine treatment on different domains of
      subjective sleep quality in Vietnam combat veterans with chronic posttraumatic
      stress disorder (PTSD). Medically healthy male Vietnam theater combat veterans (N
      = 21) completed a 10-week open label trial. Fluvoxamine treatment led to
      improvements in PTSD symptoms and all domains of subjective sleep quality. The
      largest effect was for dreams linked to the traumatic experience in combat. In
      contrast, generic unpleasant dreams showed only a modest response to treatment.
      Sleep maintenance insomnia and the item "troubled sleep" showed a large treatment
      response, whereas sleep onset insomnia improved less substantially. These
      therapeutic benefits contrast with published reports that have found activating
      effects of Selective Serotonin Reuptake Inhibitors on the sleep
      electroencephalogram.

PMID- 11534880
TI  - Dreams and exposure therapy in PTSD.
AB  - Exposure therapy is a well-established treatment for PTSD that requires the
      patient to focus on and describe the details of a traumatic experience.
      Nightmares that refer to or replicate traumatic experiences are prominent and
      distressing symptoms of PTSD and appear to exacerbate the disorder. With this
      apparent paradox in mind, exposure therapy and the literature on sleep and PTSD
      are reviewed in the context of the relationship between therapeutic exposure and
      exposure to trauma-related stimuli that occurs in dreams. It is concluded that
      nightmares that replay the trauma and disrupt sleep do not meet requirements for
      therapeutic exposure, whereas other dreaming may aid in the recovery from trauma.

PMID- 11534879
TI  - Sleep difficulties and alcohol use motives in female rape victims with
      posttraumatic stress disorder.
AB  - The purpose of this study was to assess the relationship between sleep
      difficulties and drinking motives in female rape victims with posttraumatic
      stress disorder (PTSD). Seventy-four participants were assessed for PTSD
      symptoms, depression, sleep difficulties, and drinking motives. Results
      demonstrated that neither PTSD symptoms nor depression were related to any
      motives for using alcohol. On the other hand, after controlling for education,
      sleep difficulties were significantly related to drinking motives for coping with
      negative affect, but not pleasure enhancement or socialization. The findings
      suggest that sleep difficulties may be an important factor contributing to
      alcohol use in rape victims with PTSD.

PMID- 11534881
TI  - A study of the validity of a screening instrument for traumatic stress in
      earthquake survivors in Turkey.
AB  - The validity of a Traumatic Stress Symptom Checklist (TSSC), which was developed
      as part of a Screening Instrument for Traumatic Stress in Earthquake Survivors
      (SITSES), was examined in 130 survivors of the recent earthquake in Turkey. Data
      were obtained on the TSSC, which consists of 17 DSM-IV posttraumatic stress
      disorder (PTSD) items and 6 symptoms of depression. The Clinician-Administered
      PTSD Scale and the Major Depressive Episode module of the Semistructured Clinical
      Interview for DSM-IV were used for comparison with the TSSC. The results
      indicated that the TSSC has high internal consistency and satisfactory
      sensitivity and specificity in predicting the diagnosis of PTSD and major
      depression. The SITSES appeared to be a useful instrument in screening earthquake
      survivors for PTSD, major depression, illness severity, and risk factors
      associated with traumatic stress responses.

PMID- 11534882
TI  - The effect of relocation after a natural disaster.
AB  - Twenty-five women remaining in a city devastated by an earthquake were compared
      with 24 relocated survivors and 25 comparison women. The women were administered
      a structured PTSD interview, the Hamilton Depression Scale, and SCL-90-R. The
      women in both exposed groups showed significantly more symptoms of avoidance,
      arousal, and total PTSD than the comparison group. The women in the relocated
      city had significantly higher depression scores than the women in the earthquake
      city. On the SCL-90-R, relocated women were most symptomatic and comparison group
      women were least symptomatic. Relocation after a disaster appears to be
      associated more with risk for depression than with PTSD in situations where
      recovery is delayed following the trauma.

PMID- 11534883
TI  - Evaluating psychological debriefing: are we measuring the right outcomes?
AB  - The efficacy of critical incident stress debriefing (CISD) and psychological
      debriefing (PD) following potentially traumatising events has recently been
      challenged after a number of recent randomised controlled trials (RCTs) failed to
      demonstrate that CISD or PD prevents or reduces the incidence of posttraumatic
      stress disorder (PTSD). These studies have used measures of PTSD as the principal
      outcome and have generally not measured comorbid psychopathology, behavioral or
      social dysfunction. In a recent RCT of group debriefing amongst British soldiers
      returning from peacekeeping operations in Bosnia, PD had a significant effect in
      reducing a worrying level of alcohol misuse in the sample. The findings of this
      study suggest that that it is premature to conclude that debriefing is
      ineffective and that a broader range of outcome measures should be employed in
      future trials of debriefing.

PMID- 11534884
TI  - Hardiness: an examination of its relationship with positive and negative long
      term changes following trauma.
AB  - Two models positing direct versus moderating effects of hardiness were examined
      in relation to long term positive and negative changes following exposure to
      traumatic stress. Participating in the study were 164 Israeli POWs and a matched
      group of 184 veterans of the 1973 Yom Kippur War. Participants completed a
      battery of questionnaires that included the Personal Views Survey (hardiness);
      the Trait, Attitude, and Behavior Change questionnaire; and questions related to
      their captivity/war experiences. Findings were consistent with a model that
      posits moderating effects of hardiness on both long term negative and positive
      changes. The discussion addresses the possible role of hardiness in relation to
      negative and positive outcomes of traumatic events.

PMID- 11534885
TI  - Multivariate prediction of posttraumatic symptoms in psychiatric inpatients.
AB  - Based on a conceptual framework for the long-term effects of childhood abuse,
      this study examined the capacity of childhood family environment (caretaker
      dysfunction, neglect, perceived social support), violent abuse (physical and
      sexual), and individual variables (other abuse) to predict adult psychiatric
      symptoms of PTSD, dissociation, and depression. Complete interview data were
      obtained from 178 psychiatric in patients who varied greatly on abuse status and
      severity. Results of multiple regressions of predictor variables onto the three
      outcome variables showed that the predictor variables accounted for 15% (for
      depression) to 42% (for PTSD) of the variance in these symptoms and that violent
      abuse uniquely accounted for a significant proportion of the variance in outcomes
      for all three of the symptom groups studied.

PMID- 11534886
TI  - PTSD symptoms and partner abuse: low income women at risk.
AB  - Aspects of partner abuse (types, severity, chronicity, treatment of injury, fear,
      etc.) were addressed with low income community women, half of whom scored above
      the cutoff on the Crime Related PTSD scale. Using this cutoff 47% of women who
      sustained moderate violence were high in CR-PTSD symptoms. If their partner also
      raped them, the rate (63%) was similar to women who sustained severe violence
      (65%) or severe violence and rape (71%). No ethnic differences were found for
      rates or severity of CR-PTSD symptoms. A MANCOVA by ethnicity (African Americans,
      Euro-Americans, Mexican Americans) and CR-PTSD symptoms (low vs. high) identified
      ethnic differences only on total sexual aggression and recent threats of
      violence. The high symptom group reported more abuse on all measures. Results
      from the CR-PTSD and the general lack of ethnic differences support the notion
      that SES contributes more to women's vulnerability to abuse and stress symptoms
      than does ethnicity.

PMID- 11534887
TI  - Information processing of an acquaintance rape scenario among high- and low
      dissociating college women.
AB  - To assess the impact of dissociation on information processing, 66 college women
      with high and low levels of trait dissociation were studied with regard to how
      they unitized videotape segments of an acquaintance rape scenario (actual assault
      not shown) and a nonthreatening control scenario. Unitization is a paradigm that
      measures how actively people process stimuli by recording how many times they
      press a button to indicate that they have seen a significant or meaningful event.
      Trait dissociation was negatively correlated with participants' unitization of
      the acquaintance rape videotape, unitization was positively correlated with
      danger cue identification, and state dissociation was negatively correlated with
      dangerousness ratings.

PMID- 11534888
TI  - A brief report on the Penn Inventory for posttraumatic stress disorder.
AB  - In this report we provide normative data for the Penn Inventory for posttraumatic
      stress disorder for men and women who were referred to a specialist outpatient
      clinic following a range of traumatic events. Data are provided from clinical
      assessment of 80 people. There was no significant difference between male and
      female scores. Using the Clinician Administered PTSD Scale to ascertain
      diagnostic status and Hammarberg's cut-off criterion of 35, the Penn Inventory
      showed a sensitivity of .90 for male participants and .89 for female participants
      and a specificity of .55 for male participants and .67 for female participants.
      The Penn Inventory correlated highly with other measures of psychological
      distress. We discuss that the Penn Inventory may be best used as a screening
      instrument or measure of change of general mental well-being after trauma, rather
      than a diagnostic tool for specific traumatic stress symptoms.

PMID- 11534889
TI  - Beta2-agonists--from pharmacological properties to everyday clinical practice.

PMID- 11534890
TI  - Clinical outcome of adding long-acting beta-agonists to inhaled corticosteroids.
AB  - Current asthma management guidelines state that where a patient is receiving a
      low to moderate dose of inhaled corticosteroids and is still experiencing
      symptoms the dose of corticosteroid should be increased and, if necessary, a long
      acting bronchodilator should be added. Many studies have now shown that the
      addition of a beta2-agonist with long-acting properties is more effective at
      controlling asthma symptoms than increasing the dose of corticosteroid alone. The
      Formoterol and Corticosteroid Establishing Therapy (FACET) study was a 12-month
      study comparing exacerbation rates in patients treated with budesonide (100
      microg or 400 microg) twice daily alone vs, treatment with budesonide (100 microg
      or 400 microg) twice daily plus formoterol 9 microg twice daily (delivered dose).
      The addition of formoterol reduced the rates of mild and severe exacerbations
      compared with budesonide alone, with the lowest rates seen in patients receiving
      high-dose budesonide and formoterol. There was no difference in the profile of
      exacerbations in any groups, indicating formoterol does not mask any signs of
      inflammation. The addition of formoterol to budesonide was also shown to result
      in improved lung function (as measured by peak expiratory flow rate and forced
      expiratory volume in 1 second), night-time awakenings and the use of as-needed
      medication when compared with an increase in the dose of budesonide. In all
      cases, increasing the dose of budesonide and addition of formoterol resulted in
      the most improvement and a significant increase in quality of life, measured by
      Asthma Quality of Life Questionnaire (AQLQ), was noted. In conclusion, the
      addition of formoterol to established treatment with inhaled corticosteroids
      provides superior asthma control compared with an increase in the dose of
      corticosteroid alone.

PMID- 11534891
TI  - Formoterol used as needed--clinical effectiveness.
AB  - A number of studies have already demonstrated the clinical effectiveness of
      formoterol when used as maintenance therapy in patients requiring both a beta2
      agonist with a long duration of action and a regular inhaled corticosteroid.
      However, formoterol has a unique mechanism of action that gives it both fast- and
      long-acting properties. Hence the question arises as to whether formoterol can
      also be used as first-line reliever medication in addition to maintenance
      therapy. Compared with terbutaline, formoterol used as needed in steroid-treated
      mild to moderate asthma has superior efficacy, not only significantly improving
      peak flow, but also the exacerbation rate. In moderate to severe asthma,
      formoterol used as needed has demonstrated efficacy comparable with salbutamol
      and terbutaline in improving symptoms and lung function. Single doses of
      formoterol have also been shown to result in protection against exercise-induced
      bronchoconstriction for periods up to 12 h. Furthermore, bronchoprotection was
      maintained following repeated dosing, although further research is needed to
      confirm the duration of protection achieved with frequent and regular use.
      Initial research also suggests that formoterol is as effective and well tolerated
      as terbutaline in the treatment of acute asthma attacks. The evidence presented
      supports the use of formoterol on an as-needed basis for effective asthma
      control.

PMID- 11534892
TI  - The evolution of beta2-agonists.
AB  - Beta-agonists have been widely used in the treatment of asthma for many years
      Although concerns have been expressed over their safety based largely upon
      epidemics of increased mortality in asthmatics associated with high doses of
      isoprenaline in the 1960s and fenoterol in the 1970s and 1980s, the specific
      beta2-agonists are vital drugs in asthma management. The short-acting beta2
      agonists have an important prophylactic role in the prevention of exercise
      induced bronchoconstriction, and are essential in the emergency treatment of
      severe asthma. However, little if any benefit seems to be derived from regular
      use of short-acting beta2-agonists and regular or frequent use can increase the
      severity of the condition. The development of beta2-agonists with long-acting
      properties, such as salmeterol and formoterol, has provided advantages over short
      acting beta-agonists, such as prolonged bronchodilation, reduced day- and night
      time symptoms and improved quality of sleep, and has reduced the requirement for
      short-acting beta2-agonists as relief medication. Both drugs are well tolerated
      and, when added to inhaled corticosteroids, produce greater mprovement in lung
      function than increased steroid dose alone. Because of its rapid onset of action,
      formoterol also has the potential to be used for as-needed bronchodilator therapy
      in asthma.

PMID- 11534893
TI  - Formoterol in clinical practice--safety issues.
AB  - While short-acting beta2-agonists are seen as the cornerstone of treatment as
      relief medication for asthma, current guidelines recommend long-acting beta2
      agonists as maintenance therapy in combination with inhaled corticosteroids in
      patients with moderate to severe asthma, poorly controlled on present treatment.
      Although evidence has shown that formoterol, with its fast- and long-acting
      profile, is effective when used both as regular and as-needed therapy in all
      types of asthma, there has been some concern about the potential of beta2
      agonists with long-acting profiles to produce side effects with a longer duration
      than seen with short-acting beta2-agonists. Also, where formoterol is used as
      needed, a higher total daily dose would be anticipated than when taken twice
      daily for regular maintenance therapy and this again has led to some concern. In
      a number of studies, formoterol has been shown to be well tolerated, and although
      systemic effects expected with this class of drugs did occur, formoterol had
      significantly less effect on serum potassium, pulse, blood pressure, cardiac
      frequency and QT interval compared with terbutaline. In addition, the duration of
      effects was equivalent to that observed with terbutaline and salbutamol and the
      relative therapeutic index of formoterol compared with salbutamol was found to be
      2.5. Furthermore, studies looking at long-term use of formoterol have shown there
      is no reduction in bronchodilatory effect, and thus, no development of tolerance.
      In conclusion, formoterol is well tolerated in high doses, producing side effects
      typical of its class, but with a duration no longer than occurs with short-acting
      beta2-agonists. These observations, and the lack of tolerance development,
      suggest that formoterol may be appropriate treatment for patients with asthma of
      all types and severities on an as-needed basis or as regular treatment.

PMID- 11534894
TI  - The importance of the device in asthma therapy.
AB  - Inhalation is the preferred route for drug delivery in asthma treatment.
      Successful management of asthma depends on achieving adequate delivery of inhaled
      drug to the lungs, and to this end the role of the device used for delivery is
      very important. Aerosolized anti-asthma medications have been available for more
      than 40 years as pressurized metered dose inhalers (pMDIs), but more recently dry
      powder inhalers (DPIs) have been developed as an alternative. Laboratory
      assessment of fine particle dose has been shown to correlate to pulmonary
      deposition if the assessments are performed with an in vivo-like set up. The DPI
      Turbuhaler delivers a high proportion of the dose as fine particles suggesting
      high pulmonary deposition. This finding has been confirmed by lung deposition
      studies, which indicate superior pulmonary deposition from Turbuhaler compared
      with a pMDI. This superior delivery to the lungs with Turbuhaler is reflected in
      a better clinical effect, as measured by greater improvements in lung function.
      The DPIs such as Turbuhaler are easy to use, and Turbuhaler has been shown to
      function well in a constrained situation such as an acute asthmatic exacerbation.
      Furthermore, the use of Turbuhaler in acute asthma will provide rapid clinical
      improvement. The in vivo variability in lung deposition obtained with Turbuhaler
      is lower than with pMDI, indicating that the performance of Turbuhaler is less
      dependent on patient competence. Thus, the development of Turbuhaler represents
      an important step forward in the effective management of asthma.

PMID- 11534895
TI  - Formoterol--where does it fit in the current guidelines?
AB  - Drugs available to treat asthma have improved considerably over the past three
      decades and understanding of the disease process is continually improving.
      However, the incidence of asthma is increasing and the cause(s) of this increase
      are not yet identified. Asthma is often underdiagnosed and undertreated. Poor
      compliance with medication is also an important consideration in how effective
      management strategies can be. The aim of current asthma treatment, according to
      the Global Initiative for Asthma (GINA), is to control the disease. However, two
      surveys, one in Europe and the other in the U.S.A. indicate that the objectives
      of treatment guidelines are not being met. Patients were shown to experience high
      rates of exacerbations and require many doses of reliever medication. There was
      also a large difference between patient and physician perceptions of treatment-
      this needs to be countered by improved education for both the general public and
      healthcare professionals. Formoterol, which is the only beta2-agonist to possess
      both fast- and long-acting properties, may help to improve patient compliance by
      allowing a single inhaler to be used for both maintenance and as-needed therapy.
      However, although formoterol is already widely used as maintenance therapy
      current treatment guidelines do not include the use of formoterol as first-line
      reliever medication. Evidence is increasing to support as-needed use and a large,
      randomized effect veness study in 18,000 patients across the world is ongoing to
      assess the safety and efficacy of formoterol as needed in a real-life setting.
      The results from the Real-Life Effectiveness of Oxis Turbuhaler (RELIEF) study
      should help to establish the position of formoterol as an effective first line
      reliever medication and ultimately lead to the inclusion of formoterol as needed
      in treatment guidelines.

PMID- 11534896
TI  - Pharmacological similarities and differences between beta2-agonists.
AB  - Formoterol and salmeterol are both long-acting bronchodilators that are effective
      in the treatment of asthma. However, some differences exist in their pharmacology
      that are reflected in their clinical profiles. Formoterol has a rapid onset of
      action, whereas salmeterol causes bronchodilation in a somewhat slower manner.
      However, both ofthese drugs are long-acting. After single doses clear effects are
      maintained for 12 h after inhalation, and with high doses effects are observed
      even at 24 h. Differences between the maximal effects of both drugs are also a
      consequence of their pharmacological properties. Thus, formoterol has higher
      intrinsic activity than salmeterol, which means that it is a full agonist,
      whereas salmeterol is a partial agonist on the beta2-receptor. Physicochemical
      properties of the drugs may explain the differences in onset and duration of
      action. Adequate water solubility and moderate lipophilicity of formoterol
      ensures rapid diffusion to the beta2-receptor on the smooth muscle and rapid
      bronchodilating activity. Salmeterol, on the other hand, may diffuse more slowly
      to the beta2-receptor because of its high lipophilicity explaining the slower
      onset of action. Unlike salbutamol, which is hydrophilic and has a rapid onset
      and short duration of action, both formoterol and salmeterol possess adequate
      lipophilic properties to remain in the airway tissues as a depot in close
      vicinity to the beta2-receptor, explaining their long duration of effect. The
      long duration of salmeterol has also been suggested to depend on an anchored
      binding within the beta2-receptor. The pharmacological evidence for a rapid onset
      of action of formoterol, but long duration of effect, is supported by several
      clinical studies. The fast onset of bronchodilation and high intrinsic activity
      of formoterol therefore suggest that it can be used for relief treatment in
      patients with asthma if they are concomitantly treated with inhaled
      glucocorticoids.

PMID- 11534897
TI  - Effect of clay and organic matter type on the ecotoxicity of zinc and cadmium to
      the potworm Enchytraeus albidus.
AB  - Clay and organic matter are considered as important parameters influencing
      bioavailability and ecotoxicity of metals in soils. As there exists a large
      variation in the type of clay and organic matter in field soils, the quantity of
      these variables alone may not be good indicators of metal bioavailability. To
      test this hypothesis, toxicity experiments with the potworm Enchytraeus albidus
      were conducted in artificial soils with three types of clay and seven types of
      organic matter, while the soil pH was kept constant. The 14d LC50 of zinc and
      cadmium varied from 83.0 to 1,140 mg Zn/kg D.W. and from 55.2 to 704 mg Cd/kg
      D.W., respectively, depending on the type of clay and organic matter that were
      used. Simultaneous measurements of the cation exchange capacity showed that this
      soil parameter is a better indicator of the bioavailability as it takes into
      account the type of clay and organic matter as well as other adsorption phases
      such as metal oxyhydroxides.

PMID- 11534898
TI  - The chemical and biogenotoxic characterization of organic xenobiotics in aquatic
      sediment materials 1. The application and comparison of chemically non-specific
      and biogenotoxic methods.
AB  - The aim of this work was to evaluate the Ames assay and mixed function oxidase
      (MFO)-Induct Test used in parallel with chemical group tests (ECD fingerprint and
      PAH estimation) for the characterization of the organic pollution of water
      sediment materials. Sediment materials were collected from "clean" and relatively
      heavily polluted locations in the Middle Adriatic Sea, and from some locations in
      continental Croatia polluted with wastewaters from different enterprises.
      Characterization of the organic extracts of the sediment materials investigated
      was performed chemically using UV spectrofluorometry for the determination
      polyaromatic hydrocarbons (PAH) and gas chromatography for the determination of
      volatile EC detector sensitive materials. Genotoxic analysis of the extracts was
      performed using the MFO-Induct Test and mutagenicity testing using the Standard
      Plate Incorporation Test as described by Maron and Ames with Salmonella
      typhimurium TA 98. Measurement of the BaPMO enzyme activity in the livers of carp
      treated i.p. with total extracts of the sediment investigated confirmed that the
      methanol extracts generally contained more inducing matter than the petroleum
      ether extracts. Ames assay showed that for all the samples following the
      elimination of the sulfur, there was an increase in the number of revertants in
      comparison to the control number, which indicates that the samples contained
      mutagenic substances. The larger doses of extracts generally demonstrated
      cytotoxicity, as evidenced by a reduced number of spontaneous revertants in the
      SalmonellalMicrosome Test. Investigation of the correlation of the chemical
      parameters with the biological parameter showed that the induction of BaPMO
      exhibited a statistically significant correlation with the level of the ECD
      fingerprint of the petroleum ether sediment extract.

PMID- 11534900
TI  - Combinations of Azadirachta indica and Cedrus deodara oil with piperonyl
      butoxide, MGK-264 and Embelia ribes against Lymnaea acuminata.
AB  - The binary and tertiary combinations of plant-derived molluscicides Azadirachta
      indica and Cedrus deodara oil with synergists MGK-264, piperonyl butoxide (PB)
      and fruit powder of Embelia ribes were used against the Lymnaea acuminata. It was
      observed that the toxic effects of these mixtures were time- and dose-dependent.
      The binary and tertiary mixtures of plant-derived molluscicides with synergists
      were more toxic with respect to the single treatment of the plant-derived
      molluscicides. Maximum synergistic action in binary and tertiary combinations was
      found in A. indica + C. deodara oil and A. indica+ PB + C. deodara in 1:7 and
      1:5:7 ratio, respectively.

PMID- 11534899
TI  - Effects of atrazine on acetylcholinesterase activity in midges (Chironomus
      tentans) exposed to organophosphorus insecticides.
AB  - Acetylcholinesterase activity was determined for midge larvae (Chironomus
      tentans) exposed to either organophosphorus insecticides (OPs) alone or OP
      insecticides in binary combination with atrazine (200 microg/l). Although
      atrazine by itself did not reduce the level of acetylcholinesterase activity,
      atrazine in combination with chlorpyrifos significantly decreased
      acetylcholinesterase activity as compared to chlorpyrifos only treatments.
      Although similar trends existed for malathion and methyl parathion, differences
      were not statistically significant. These results match previously published
      toxicity data where atrazine, although not acutely toxic even at much higher
      levels, decreased EC50 values for chlorpyrifos by a magnitude of 4, decreased
      methyl parathion values by a magnitude of 2, and did not decrease values for
      malathion.

PMID- 11534901
TI  - Bioconcentration of nonylphenol in fathead minnows (Pimephales promelas).
AB  - Bioconcentration of p-nonylphenol (NP) by fathead minnows was determined under
      laboratory conditions. Fish were exposed continuously for 42 days to 0.33, 0.93
      and 2.36 microg NP/l in a flow-through system. NP was Soxhlet extracted from
      whole fish homogenates with dichloromethane (DCM). The resulting extract was
      concentrated and bulk lipids removed by gel permeation and silica-gel
      chromatography. Compounds were identified and quantified by reverse-phase high
      pressure liquid chromatography (RP-HPLC) with fluorescence detection. Mass
      spectrometry was used for verification of peak assignments. Bioconcentration
      factors (BCFs) ranged from 245 to 380.

PMID- 11534902
TI  - A study of 2,4,6-trinitrotoluene inhibition of benzo[a]pyrene uptake and
      activation in a microbial mutagenicity assay.
AB  - A number of in vitro and in vivo studies have determined that binary and complex
      mixtures may interact to produce a toxicity that could not be predicted based on
      the individual chemicals. The present study was conducted with a binary mixture
      of model compounds to investigate possible interactions affecting their
      mutagenicity. The compounds included Benzo[a]pyrene (BAP), a polycyclic aromatic
      hydrocarbon that is an indirect-acting mutagen of great environmental concern,
      and 2,4,6-Trinitrotoluene (TNT), a nitro-aromatic compound that is a direct
      acting mutagen frequently found as a soil contaminant at munitions sites. This
      study indicated that a binary mixture of BAP and TNT failed to induce the
      positive mutagenic response in Salmonella typhimurium strain TA98 characteristic
      of either compound alone. Spectrofluorometric analysis of BAP, and kinetic
      analyses of 3HBAP uptake in the presence or absence of TNT using TA98 cells that
      were treated or untreated with activated rat liver microsomes were performed. In
      cells preloaded with BAP, cellular BAP fluorescence was rapidly suppressed in the
      presence of TNT. Mass spectroscopy of BAP and TNT mixtures revealed a number of
      products, believed to be the result of complexation and nitration, that may
      account for the antagonistic action of TNT on BAP-induced mutagenicity in TA98
      cells. Further, kinetic studies indicated that TNT inhibited the incorporation of
      BAP into cells.

PMID- 11534903
TI  - Validation of germination rate and root elongation as indicator to assess
      phytotoxicity with Cucumis sativus.
AB  - Germination rate and root elongation, as a rapid phytotoxicity test method,
      possess several advantages, such as sensitivity, simplicity, low cost and
      suitability for unstable chemicals or samples. These advantages made them
      suitable for developing a large-scale phytotoxicity database and especially
      applicable for developing quantitative structure-activity relationship (QSAR) to
      study mechanisms of phytotoxicity. In this paper, the comparative inhibition of
      germination rate and root elongation of Cucumis sativus by selected halogen
      substituted phenols and anilines were determined. The suitability of germination
      rate and root elongation as phytotoxicity endpoints was evaluated. Excellent
      reproducibility and stability of germination rate and root elongation in the
      control test, relatively greater sensitivity and similar dose-response relations
      for all tested compounds were observed. These results together with those of a 2
      day test were used to demonstrate the suitability of this phytotoxicity test
      method. A QSAR was developed for the phytotoxicity mode of action of the tested
      compounds to C sativus seeds. Models that combined the logarithm of 1
      octanol/water partition coefficient (log Kow) and the energy of the lowest
      unoccupied molecular orbital (Elumo) were developed for both germination rate
      inhibition and root elongation inhibition. The results of these studies indicate
      that phytotoxicity of substituted phenols and anilines to C. sativus seeds could
      be explained by a polar narcosis mechanism. This paper will promote the
      application of germination rate and root elongation method and the development of
      large-scale phytotoxicity database, which will provide the fundamental data for
      QSAR and ecological risk assessment of organic pollutants.

PMID- 11534904
TI  - Urban airborne particulate: genotoxicity evaluation of different size fractions
      by mutagenesis tests on microorganisms and comet assay.
AB  - The genotoxic effects of different size fractions of airborne particulate (Total,
      PM10 and PM25), extracted with acetone or toluene, were evaluated by: the Ames
      plate test (TA98 and TA100 strains, w/o S9), gene conversion and reversion (w/o
      endogenous metabolic activation) in the Saccharomyces cerevisiae D7 strain, and
      the comet assay on human leukocytes. The data on human leukocytes confirm the
      sensitivity of the comet assay and its applicability to assess genotoxicity in
      environmental samples. The PM2.5 fraction of airborne particulate generally shows
      the highest concentration of DNA-damaging compounds. Genotoxic response, in all
      the test systems applied, is highly dependent on extraction solvent used. Acetone
      seems to extract compounds with more similar genotoxic responses in the three
      test systems used than toluene extracts. Toluene appears to extract air
      pollutants genotoxic on yeast and leukocytes but is mainly cytotoxic on
      Salmonella.

PMID- 11534905
TI  - Ecotoxicological and chemical evaluation of phenolic compounds in industrial
      effluents.
AB  - The aim of this paper was to evaluate the ecotoxicological response of industrial
      effluents containing phenolic compounds. All complex effluents collected from a
      chemical plant and then after both a chemical-physical and biological treatment
      were characterised with chemical analysis, biodegradability tests and four
      ecotoxicological tests (Daphnia magna, Artemia salina, Brachionus plicatilis and
      Vibriofisheri with Microtox). The evaluation of the chemical and ecotoxicological
      data was useful for predicting the effect of the raw effluent on the treatment
      plant and the impact of the final treated effluent on the receiving water.
      Besides the toxicity of the effluent from the chemical plants, the acute toxicity
      of its main components was also determined. The results of the tests and toxicity
      data from literature were transformed in Toxic Units (TUs). Effluent toxicity was
      under- or over-estimated by calculating the sum of the TUs of the individual
      components, depending on which toxicity data and test organisms were used.

PMID- 11534906
TI  - Influence of water hardness on the bioavailability and toxicity of linear
      alkylbenzene sulphonate (LAS).
AB  - In the present work, the influence of Ca2+ concentration on the toxicity of
      single cut linear alkylbenzene sulfonate (LAS) homologues was studied.
      Precipitation boundary diagrams for each homologue were obtained, indicating
      turbid and clear zones depending on the LAS and Ca2+ concentrations. The
      separation between transparent and turbid zones is given by the so-called
      precipitation line. LAS toxicity to Daphnia magna was determined at
      concentrations close to this precipitation line. It was observed that when
      Ca(LAS)2 precipitation progresses, LAS bioavailability decreases for test
      animals, and the toxicity diminishes even at high nominal LAS concentrations.
      According to the "free ion activity model" (FIAM), the toxicity of a given
      chemical compound is mainly due to the ionic species (Ca2+-LAS-) and not due to
      the precipitated molecule, Ca(LAS)2. The significance of the present study is in
      connection with the assessment of LAS sorption/precipitation studies in soils and
      sediments, where in situ toxicity is strongly influenced by Ca2+/Mg2+ ions,
      according to the results presented in this work.

PMID- 11534907
TI  - Long-term assessment of insecticides treatments in West Africa: aquatic
      entomofauna.
AB  - For the control of the Onchocerca volvulus vector in West Africa, up to 18,000 km
      of rivers from 1975 and up to 50,000 km from 1989 had been partly sprayed weekly
      with insecticides as part of the Onchocerciasis Control Programme (OCP). To
      evaluate the possible short-term and long-term effects of the application of
      insecticides on the non-target fauna, an aquatic monitoring programme was set up
      during the initial phase of the programme. By analysing the invertebrate data,
      which were collected using various sampling strategies from four different
      countries between 1977 and 1996, this paper evaluates the long-term changes of
      the invertebrate populations with respect to their taxonomic composition as well
      as their trophic structures. The discussed results of the applied numerical
      analysis strategy suggest that neither the taxonomic nor the trophic structures
      are greatly altered from the range of biological, flow-related variation that
      normally occurs in the studied river systems. This allows us to conclude that the
      biological variation found here is ecologically acceptable.

PMID- 11534908
TI  - Effects of pyridaphenthion on growth of five freshwater species of phytoplankton.
      A laboratory study.
AB  - The acute toxicity of the insecticide and acaricide pyridaphenthion to five
      species of freshwater phytoplankton, Scenedesmus acutus, Scenedesmus subspicatus,
      Chlorella vulgaris, Chlorella saccharophila and Pseudanabaena galeata was
      determined. Insecticide concentrations eliciting a 50% growth reduction over 96 h
      (EC50) ranged from 2.2 to 30.9 mg/l. The two species of Chlorella and the
      cyanobacteria P. galeata were more tolerant than the two species of Scenedesmus.
      Concentrations of pyridaphenthion detected in some natural waters were less than
      the toxic threshold for these species.

PMID- 11534910
TI  - Neutrophilic eccrine hidradenitis in a patient with Behcet's disease.
AB  - Patients with Behcet's disease may develop multiple mucocutaneous manifestations,
      several of which are mediated by neutrophils. These include aphthous ulcers,
      pseudofolliculitis, acneform lesions, and pathergy. We report another neutrophil
      mediated disorder, neutrophilic eccrine hidradenitis (NEH), in a patient with
      Behcet's disease. NEH should be added to the list of mucocutaneous lesions that
      may be seen in patients with Behcet's disease.

PMID- 11534909
TI  - Primary multiple miliary osteoma cutis and exogenous ochronosis.
AB  - Multiple miliary osteoma cutis (MMOC), a rare disorder characterized by the
      appearance of numerous bony nodules on the face, was initially classified as a
      consequence of severe, long-standing acne vulgaris. However, several cases have
      now been described in patients with no preceding history of acne or other
      inflammatory conditions. We report such a case of primary MMOC in a 75-year-old
      African American woman and highlight the differences between these conditions. We
      also note the incidental histologic finding of exogenous ochronosis, which, in
      our case, indicates the patient's use of hydroquinone-containing bleaching creams
      in an attempt to treat the disorder.

PMID- 11534911
TI  - The ocular manifestations of rosacea.
AB  - The ocular manifestations of rosacea are commonly nonspecific and variable. The
      etiology of the inflammation is unknown and there is no diagnostic test for the
      disease. Ocular rosacea is often underdiagnosed, despite the potential for
      serious sight-threatening sequelae. When evaluating patients with rosacea,
      dermatologists should obtain a careful history of eye complaints and examine the
      eyelid margins thoroughly. Treatment is aimed at controlling symptoms and is
      multifaceted. The foundation of treatment is good lid hygiene and oral
      tetracyclines. Those patients with moderate-to-severe ocular findings will
      benefit from a multidisciplinary approach, including evaluation by an
      ophthalmologist.

PMID- 11534912
TI  - Concurrent herpes simplex type 1 and varicella-zoster in the V2 dermatome in an
      immunocompetent patient.
AB  - A unique feature of herpesviruses is their ability to establish latent infection
      within the nervous system by colonizing peripheral sensory ganglia, which results
      in subsequent episodic outbreaks of infection triggered by precipitating events.
      Despite the latent nature of both herpes simplex virus type 1 (HSV-1) and
      varicella-zoster virus (VZV) within these sensory ganglia, simultaneous outbreaks
      of these viruses are uncommon. This is generally attributed to the differing
      reactivation features of these 2 viruses. Four cases of concurrent HSV-1 and VZV
      infection are described in the literature. We report concurrent infection of HSV
      1 and VZV within the same V2 dermatome in an immunocompetent patient.

PMID- 11534913
TI  - Becker's nevus syndrome.
AB  - Becker's nevus (BN) is a unilateral hyperpigmented, often hairy, cutaneous
      hamartoma, with geographic borders. It is usually localized on the shoulder,
      anterior chest, scapula, or upper arm, but there have been reports of BN in other
      areas (eg, lower extremities, face). In most cases, the lesion appears in late
      childhood or adolescence, and both congenital and familial cases have been
      described.

PMID- 11534914
TI  - Infantile acute hemorrhagic edema of the skin.
AB  - Infantile acute hemorrhagic edema (AHE) of the skin is an uncommon form of
      cutaneous leukocytoclastic vasculitis that occurs in children younger than 3
      years. We describe a 10-month-old boy with AHE, in whom the disease appeared
      after antibiotic treatment for an acute respiratory illness. AHE presented with
      fever, acral edema, and rosette-shaped purpuric plaques on the face and limbs.
      The causes of AHE are unclear, as is its nosologic position. Some authors
      consider the disease as a purely cutaneous form of Henoch-Schonlein purpura, and
      others believe that AHE should be regarded as a distinct clinicobiologic entity
      within the spectrum of leukocytoclastic vasculitis.

PMID- 11534915
TI  - Tretinoin cream 0.02% for the treatment of photodamaged facial skin: a review of
      2 double-blind clinical studies.
AB  - In extensive clinical studies and practical use since its US Food and Drug
      Administration approval in 1995, tretinoin emollient cream 0.05% has been shown
      to be safe and effective in the treatment of fine facial wrinkles, mottled
      hyperpigmentation, and skin roughness. To provide additional prescribing
      flexibility for various patient needs, a new lower concentration formulation,
      tretinoin cream 0.02% was chosen for further development. Two multicenter,
      randomized, double-blind, vehicle-controlled clinical., studies were conducted to
      evaluate the safety and efficacy of the lower concentration tretinoin formulation
      in the treatment of moderate-to-severe facial photodamage. Results indicate
      statistically significant improvement in fine wrinkling, coarse wrinkling, and
      yellowing with the use of tretinoin cream 0.02% at week-24 end point, compared
      with placebo. Therapy with tretinoin cream 0.02% was well tolerated overall and
      demonstrated a favorable safety profile. Both studies demonstrated that tretinoin
      cream 0.02% is safe and effective for the treatment of moderate-to-severe
      photodamaged facial skin.

PMID- 11534916
TI  - Porphyria cutanea tarda associated with an acute gastrointestinal bleed: the
      roles of supplemental iron and blood transfusion.
AB  - We describe a case of porphyria cutanea tarda (PCT) induced by blood transfusion
      and oral iron supplementation in an 80-year-old white woman. The patient
      experienced acute blood loss from 2 duodenal ulcers 2 months prior to
      presentation. During her hospitalization for the gastrointestinal bleed, her
      anemia was treated with blood transfusion, iron supplementation, and
      erythropoietin. Multiple blistering lesions developed on her skin 2 months after
      hospital discharge. Clinical and laboratory findings were consistent with a
      diagnosis of porphyria cutanea tarda. Treatment included discontinuation of iron
      therapy, local skin care, and phlebotomy, which prevented the development of more
      lesions. The roles of iron overload and chronic renal disease in the pathogenesis
      of the porphyria are discussed.

PMID- 11534917
TI  - Investigation of the allergenicity of a refined peanut oil-containing topical
      dermatologic agent in persons who are sensitive to peanuts.
AB  - We determined if a topical oil containing 0.01% fluocinolone and refined peanut
      oil (Derma-Smoothe/FS topical oil), among other ingredients, included materials
      to which peanut-sensitive individuals were sensitized. No immediate (15-min) or
      delayed (72-h) skin test reactivity was demonstrated in any of the 14 subjects
      tested. These results suggest that this refined peanut oil-containing
      dermatologic preparation is safe to use, even in persons who are sensitive to
      peanuts.

PMID- 11534918
TI  - Women commonly seek care for rosacea: dermatologists frequently provide the care.
AB  - Rosacea is a common dermatosis affecting the central portion of the face. The
      purpose of this study is to describe the demographics of patients and the
      treatments prescribed. Data on rosacea visits from 1990 to 1997 were obtained
      from the National Ambulatory Medical Care Survey There were 1.1 million
      outpatient visits for rosacea annually in the United States. Most rosacea
      patients were Caucasian (96%). Most visits were by women (69%), and the mean age
      (SD) of patients was 50 +/- 17 years. Visits to dermatologists accounted for 78%
      of visits. Common comorbid diagnoses included actinic keratoses, acne and cysts,
      and seborrheic and contact dermatitis. Topical metronidazole was the most
      commonly prescribed treatment; tetracycline was the most commonly prescribed
      systemic therapy. Combination treatment with an oral and a topical agent was
      commonly used. Because rosacea appears most often in fair-skinned women, these
      patients may benefit from the textural features and safety profiles of certain
      topical metronidazole preparations newly available and from oral antibiotics (eg,
      tetracycline). People with rosacea should be aware of the experience that
      dermatologists have in treating this disorder.

PMID- 11534919
TI  - Rosacea and adult acne: a worldwide epidemic.

PMID- 11534920
TI  - Treatment of alpha1-antitrypsin-deficiency panniculitis with minocycline.
AB  - A small proportion of patients with alpha1-antitrypsin (alpha1AT) deficiency
      experience recurrent ulcerating panniculitis. Studies suggest that alpha1AT
      deficiency panniculitis reflects an uncontrolled inflammatory process because of
      the serum's incapacity to neutralize proteolytic enzymes released by leukocytes
      in the skin. Dapsone is considered the treatment of choice for this entity, but
      it is limited by its side effects, especially hematologic ones. Tetracyclines
      have anticollagenase and anti-inflammatory activity and have been used
      successfully to treat this type of panniculitis. We report the case of a 42-year
      old woman with recurrent alpha1AT-deficiency panniculitis who did not tolerate
      the side effects of dapsone or systemic corticosteroid. Minocycline treatment led
      to disappearance of lesions, and long-term administration prevented recurrences
      without evident negative side effects. We consider minocycline a safe treatment
      that allows control of alpha1AT-deficiency panniculitis.

PMID- 11534921
TI  - Papular urticaria.
AB  - Papular urticaria is a common and often distressing childhood disorder manifested
      by chronic or recurrent papules caused by a hypersensitivity reaction to the
      bites of mosquitoes, fleas, bedbugs, and other insects. Individual papules may
      surround a wheal and often have a central punctum. The histopathology of papular
      urticaria consists of mild subepidermal edema, extravasation of erythrocytes,
      interstitial eosinophils, and exocytosis of lymphocytes. Papular urticaria may
      represent a clinical challenge, particularly during spring and summer months.

PMID- 11534922
TI  - Photo quiz. Inherited palmoplantar keratoderma (Unna-throat disease).

PMID- 11534923
TI  - What's eating you? Demodex folliculorum.

PMID- 11534924
TI  - Dermatologic surgery into the next millennium, part II.
AB  - This is the second article in a 4-part series on dermatologic surgery. This
      section provides detailed information about filling agents and botulinus toxin A.
      The filling agents discussed here are frequently used in our office. It is
      emphasized that meticulous technique and patient selection predict a good
      cosmetic result. To select the right agent, patient safety must be a priority.

PMID- 11534925
TI  - Glucose metabolism in relation to schizophrenia and antipsychotic drug treatment.
AB  - It has been reported in the earlier literature that many patients with psychoses
      had abnormalities in glucose metabolism as revealed by glucose tolerance testing.
      This observation is reinforced by the fact that the schizophrenic population
      appears to have about a 2-3-fold increased risk for Type II diabetes mellitus.
      However, some uncertainty remains about the relative risk value because there
      have been numerous case reports of patients who developed hyperglycemia and even
      Type II diabetes apparently as a consequence of treatment with antipsychotic
      drugs. Schizophrenic patients with abnormal glucose metabolism have a higher
      prevalence of drug-induced tardive dyskinesia than patients with a normal glucose
      profile. Treatment with the new atypical antipsychotics has a much lower risk of
      movement disorders; however, weight gain, hyperglycemia, and diabetes are
      emerging as significant side effects. Because glucose is essential for energy
      metabolism in neurons, any change in the effective glucose levels in brain that
      result from drug therapy may have significant clinical implications. It is not
      clear whether the glycemic state of schizophrenics contributes to their psychotic
      symptoms or modulates the incidence of drug side effects. Basic research shows
      that the drugs which cause hyperglycemia in patients appear to inhibit neuronal
      glucose transport which may partly explain their effects. This paper reviews the
      relevant literature in a preliminary attempt to understand the implications of
      such clinical findings in the light of basic research.

PMID- 11534926
TI  - 2nd year maintenance and discontinuation of imipramine in panic disorder with
      agoraphobia.
AB  - BACKGROUND: The results from our 1 year placebo-controlled
      maintenance/discontinuation study in remitted panic disorder with agoraphobia
      patients confirmed the significant prophylactic effectiveness of imipramine
      maintenance treatment but suggested that this may be necessary in only 37% of the
      patients who relapse following discontinuation of 6 months acute imipramine
      treatment. This paper presents pilot data from a second year extension of the
      above-mentioned study with the aim of exploring the putative protective effects
      of maintenance imipramine therapy beyond the 1st year. METHOD: Eighteen patients
      from the 30 who survived, in stable remission, the first 12 months of the
      maintenance/discontinuation study gave written consent to participate in a double
      blind 2nd year extension phase with the knowledge that those on placebo will
      continue on the same condition (N = 7, PBO-PBO) and those on imipramine (N = 11)
      will be rerandomized to 2nd year maintenance (N = 4, IMI-IMI) or placebo
      substitution (N = 7, IMI-PBO). The procedures continued unchanged from that of
      the 1st year of the study and patients were followed with planned assessments
      every 2 months over the second 12-month experimental period of the study.
      RESULTS: None of the IMI-IMI patients relapsed, two (28.5%) of the IMI-PBO
      patients relapsed, and two (28.5%) of PBO-PBO patients relapsed. The mean
      estimated time without relapse was 10 months and 9 months for IMI-PBO and PBO
      PBO, respectively. The estimated probability of not relapsing was .64 for IMI-PBO
      and .60 for PBO-PBO (Mantel-cox test chi2 =.84, p = .77). CONCLUSION: These
      interlocking controlled observations tentatively suggest that a substantial
      degree of prophylactic efficacy continues and that a substantial need for
      continued prophylaxis exists beyond the 1st year of maintenance imipramine
      treatment in panic disorder with agoraphobia patients.

PMID- 11534927
TI  - Does EEG predict response to valproate versus lithium in patients with mania?
AB  - A number of factors may suggest that a patient with mania may respond to
      valproate or to lithium. However, prediction of which patients will respond to
      either medication remains difficult. In this study nonepileptiform EEG
      abnormalities in responders to each medication were investigated. Six of 20
      patients (30%) responsive to lithium but not to valproate had nonepileptiform EEG
      abnormalities while 14 of 20 patients (70%) responsive to valproate but not to
      lithium had nonepileptiform EEG abnormalities. Patients presenting with mania and
      EEG abnormalities, particularly sharp activity, are statistically more likely
      (chi2 = 4.9, df = 1, p = .027) to respond to valproate than to lithium. Whether
      such a finding will also hold true for other anticonvulsants used to treat mania
      remains to be seen.

PMID- 11534928
TI  - Bioavailable testosterone as a correlate of cognition, psychological status,
      quality of life, and sexual function in aging males: implications for
      testosterone replacement therapy.
AB  - Andropause is a syndrome described in aging males, is composed of a constellation
      of physical, sexual, and emotional symptoms, and is thought to be related to
      declining concentrations of serum testosterone. Numerous studies of testosterone
      replacement therapy in elderly hypogonadal males have documented the physical
      benefits of such treatment, but have failed to assess cognition, psychological
      functioning, and quality of life. Male outpatients greater or equal to 55 years
      of age completed cognitive, psychological, sexual, and quality of life
      assessments. A serum sample was provided for bioavailable testosterone assay. The
      associations between bioavailable testosterone concentrations and
      neuropsychological testing were assessed using Spearman rank correlation.
      Overall, bioavailable testosterone was not an important determinant of cognitive,
      psychological, or sexual functioning or of quality of life. The implications for
      future studies involving testosterone replacement therapy are discussed.

PMID- 11534929
TI  - A prospective study of coping after exposure to a mass murder episode.
AB  - In a study of 136 survivors of a mass murder spree, multidimensional scaling
      identified clusters of responses mapping from 75 coping behaviors described by
      victims. This powerful method identified three coping dimensions: (a) Active
      Outreach versus Passive Isolation, (b) Informed Pragmatism versus Abandonment of
      Control, and (c) Reconciliation/Acceptance versus Evading the Status Quo. These
      coping dimensions were used to predict change in psychiatric status prospectively
      assessed with structured diagnostic interviews at index 3-4 months after the
      event and follow-up assessments 1 and 3 years later. Statistically significant
      changes in the positive direction on each of the three dimensions in this study
      were associated with reductions of 47-79% of the odds for acute postdisaster
      major depression, posttraumatic stress disorder (PTSD), and any non-PTSD
      disorder. These findings suggest mechanisms for development of therapeutic
      techniques capitalizing on encouraging active outreach, informed focus and
      pragmatism, and reconciliation and acceptance, and reduction of passive and
      isolative behaviors, resignation of control, and avoidance of realities of the
      postdisaster situation.

PMID- 11534930
TI  - Neurocognitive and symptom correlates of self-reported childhood sexual abuse in
      schizophrenia spectrum disorders.
AB  - This study examined whether self-reported childhood sexual abuse in schizophrenia
      spectrum disorders is linked with severity of neurocognitive deficits. The
      Wisconsin Card Sorting Test, California Verbal Learning Test, and select WAIS III
      subtests were administered to 15 participants with schizophrenia or
      schizoaffective disorder who had been sexually abused and to 28 participants with
      no abuse history. Controlling for age and premorbid IQ, a MANCOVA indicated there
      were group differences (f(9, 31) = 5.53, p < .001). Subsequent ANCOVA indicated
      that the sexual abuse group performed more poorly on tests of working memory and
      information processing speed. Childhood sexual abuse is associated with more
      severe working memory deficits in adults with schizophrenia spectrum disorders.

PMID- 11534931
TI  - Sleep and suicide in psychiatric patients.
AB  - Suicidal patients often report problems with their sleep. Although sleep-related
      complaints and EEG (electroencephalographic) changes have been seen widely across
      the spectrum of psychiatric disorders, sleep complaints such as insomnia,
      hypersomnia, nightmares, and sleep panic attacks are more common in suicidal
      patients. The subjective quality of sleep as measured by self-rated
      questionnaires also appears to be more disturbed in suicidal depressive patients.
      Sleep studies have reported various polysomnographic findings including increased
      REM (rapid eye movement) time and REM activity in suicidal patients with
      depression, schizoaffective disorder, and schizophrenia. One mechanism
      responsible for this possible association between suicide and sleep could be the
      role of serotonin (5HT). Serotonergic function has been found to be low in
      patients who attempted and/or completed suicide, particularly those who used
      violent methods. Aggression dyscontrol appears to be an intervening factor
      between serotonin and suicide. Additionally, agents that enhance serotonergic
      transmission decrease suicidal behavior. Serotonin has also been documented to
      play an important role in onset and maintenance of slow wave sleep and in REM
      sleep. CSF 5-HIAA levels have been correlated with slow wave sleep in patients
      with depression as well as schizophrenia. Moreover, 5HT2 receptor antagonists
      have improved slow wave sleep. Further studies are needed to investigate the
      possible role of sleep disturbance in suicidal behavior.

PMID- 11534932
TI  - The metabolic puzzle during the evolution of HIV infection.
AB  - Abnormalities in energy, protein, lipid and glucose metabolism have been
      described in HIV patients since the beginning of the epidemic. With the new
      antiretroviral agents, nutritional status and survival have improved
      dramatically. However, since these therapies were introduced, there have been
      more descriptions of metabolic abnormalities, some of which were similar to and
      others of which were in conflict with those reported in previous years. This
      paper reviews the complexity of the metabolic abnormalities in HIV infections
      before and after the introduction of highly active antiretroviral therapy, and
      discusses such etiopathogenic mechanisms as secondary infections, antiretroviral
      drugs and persistent immune activation, which may be involved in these
      derangements.

PMID- 11534933
TI  - Maternal dietary PUFAs intake and human milk content relationships during the
      first month of lactation.
AB  - Maternal dietary fatty acids (FFAs) intake and corresponding human milk
      composition relationships have been assessed throughout the first month of
      lactation in 34 lactating women consecutively enrolled. All mothers were on their
      habitual diet. Food records (95 items) were administered to the mothers, six
      times during the first month of lactation (1 day after delivery, 4, 7, 14, 21,
      and 28 days after colostrum appearance) and referred to maternal dietary intake
      of the day before. Milk collected on day 1 was considered as colostrum, day 4 and
      7 samples as transitional milk, and day 14, 21 and 28 samples as mature milk.
      Five gas chromatographic analyses were performed on each sample. Statistics were
      made using Friedman's and Pearson's test. Maternal dietary saturated fatty acids
      (SFAs) and monounsaturated fatty acids (MUFAs) were significantly related to the
      corresponding milk pattern in the phase of transitional milk (P<0.01), while
      total polyunsaturated (PUFAs) content was significantly related only to the
      mature milk (P<0.01); in this phase about 42% of the variations occurring in
      PUFAs milk content can be related to variation of maternal PUFAs dietary intake.
      The results in the present study provide evidence of the relationships between
      maternal diet and milk composition. The degree of correlation between maternal
      diet and PUFAs milk content increases throughout milk maturational process and
      reaches significance only in mature milk. This would imply that advancing
      lactation, milk PUFAs provision sources gradually shift from adipose tissue
      catabolism to maternal diet.

PMID- 11534934
TI  - Altered subjective appetite parameters in Crohn's disease patients.
AB  - BACKGROUND AND AIM: Altered appetite and early satiety may promote anorexia
      associated with Crohn's disease. The aim of this study was to assess the impact
      of disease activity on subjective appetite parameters in Crohn's disease
      patients. METHODS: Seventeen patients with Crohn's disease and 15 healthy
      controls (8 M: 7 F, 34 (20-35) years) were studied. Subjects rated their hunger,
      desire to eat, fullness and level of satiety using visual analogue scales after
      an overnight fast. Subjects were reassessed after ingestion of 500 and 1000 ml
      water. Anthropometry was used to determine percentage body fat. Serum leptin &
      TNF- alpha levels were assessed using immunoassay. Disease activity was
      determined using the Harvey-Bradshaw index. RESULTS: Hunger ratings for active
      Crohn's disease patients were significantly lower than controls at baseline
      (P<0.05). Desire to eat was lower in patients with active Crohn's disease than
      controls both at baseline (95% CI, 0.3 mm, 40.7 mm) and after ingestion of 500 ml
      water (95% CI, 1.25 mm, 51.9 mm) (P<0.05). Serum leptin concentrations were
      significantly associated with percent body fat (r=0.57;P<0.001) and, after
      correcting for body fat status, tended to be higher in patients with active
      Crohn's disease (mean 0.9 ng/ml/% body fat; SD 0.8 ng/ml/% body fat) compared
      with either patients with inactive disease (mean 0.4 ng/ml/% body fat; SD 0.3
      ng/ml/% body fat) or healthy controls (mean 0.3 ng/ml/% body fat; SD 0.2 ng/ml/%
      body fat) (P=0.15, ns). Appetite parameters and serum leptin concentrations
      showed no significant correlation. CONCLUSIONS: Subjective appetite parameters
      were altered in patients with active Crohn's disease. At baseline, patients with
      active Crohn's disease were less hungry than healthy controls and had less desire
      to eat. After ingestion of 500 ml of water, desire to eat was significantly less
      in patients with active disease as compared with healthy controls. Serum leptin
      concentration corrected for percent body fat tended to be higher in patients with
      active Crohn's disease compared with inactive Crohn's disease and healthy
      controls, but the differences did not reach statistical significance.

PMID- 11534935
TI  - Amino acid metabolism during total parenteral nutrition in healthy volunteers:
      evaluation of a new amino acid solution.
AB  - The aim of this study was to determine the metabolism and the tolerance of a new
      amino acid (AA) solution administered under conditions mimicking cyclical
      parenteral nutrition (PN) in humans. Eight healthy volunteers received peripheral
      PN for 10 h providing 10.5 mg N x kg(-1) x h(-1) and 2.0 kcal x kg(-1) x h(-1)
      (glucose-to-lipids ratio: 70/30%). For adaptation, a non-protein energy intake
      was increased progressively for 90 min; thereafter, AA infusion was started and
      maintained at a constant rate for 10 h. Plasma and urine concentrations of all
      the AAs were measured before, during and after the PN. For each given AA, the
      relation between plasma variations at the steady-state and infusion rate, plasma
      clearance (Cl), renal clearance (Clr), re-absorption rate (Reab) and, retention
      rate (Reten) were determined. The nitrogen balance (DeltaN) was calculated during
      the PN period. The results are presented as means+/-sem. All plasma AA
      concentrations decreased during the starting period of non-protein energy intake.
      The plasma AA concentrations reached a steady-state within 3 h upon AA infusion,
      except for glycine and lysine (6 h). At the steady state, the plasma
      concentrations of the infused AAs were closely correlated to their infusion rate
      (y= -18.3+1.5x, r(2)=0.92). The plasma glutamine concentration was maintained
      during the PN, which indicates that the solution might stimulate the de novo
      synthesis of this AA. When the PN was stopped, plasma levels of the AAs
      decreased, most of them returning to their basal levels, or significantly below
      for lysine (P<0.05), alanine (P<0.05), proline (P<0.01) and glutamine (P<0.05).
      No volunteer showed any adverse effect during the infusion period. DeltaN was:
      0.8+/-0.5 gN/10 h. Metabolic characteristics for essential AAs were: Cl<0.5 l
      min(-1), Clr <1.5 ml x min(-1) Reab >or= 99%, Reten >or=99% and for non-essential
      AAs: Cl <0.6 l x min(-1) except aspartate (2.8+/-0.3 l x min(-1)), Clr < 3 ml x
      min(-1) except glycine (6.8+/-0.7), aspartate (8.2+/-3.5) and histidine (8.8+/
      1.3); Reab >or= 98% except glycine (95+/-1), aspartate (94+/-2) and histidine
      (94+/-1), Reten >or=97% except histidine (94+/-1), glycine (95+/-3). These
      results indicate that in healthy subjects, the amounts of AAs provided by the new
      solution were well balanced for an intravenous administration, and so were well
      utilized without excessive urinary excretion. The present study provides useful
      metabolic parameters for a further evaluation in disease.

PMID- 11534936
TI  - Effect of L-arginine on the course of experimental colitis.
AB  - BACKGROUND AND AIMS: L-Arg is the substrate for nitric oxide, and also for L
      ornithine which, in turn, is the precursor for the synthesis of collagen and
      polyamines. By these different metabolic pathways, L-Arg is involved in the
      mechanisms of inflammation, tissue repair and fibrosis. Thus, the aim of this
      study was to assess the effect of both different amounts of L-Arg supplementation
      and L-Arg-free diets upon colonic inflammatory damage and fibrosis in
      experimental colitis. METHODS: Sprague-Dawley rats with trinitrobenzene sulphonic
      acid (TNBS)-induced colitis received increasing doses of L-Arg (30, 100, 500
      mg/day), or D-Arg (500 mg/day). In a second experiment, two L-Arg-free diets (one
      supplemented with L-Gly) were compared to a L-Arg diet. Nitrite/nitrate release
      in the lumen of the colon and colonic damage were evaluated. In the first
      experiment, tissue collagen levels and colonic mucosal proliferation were also
      assessed. RESULTS: In the acute phase of colitis, intracolonic nitrite/nitrate
      levels were significantly higher in the 100 and 500 mg supplemented L-Arg groups
      than in D-Arg group. However, only rats treated with 500 mg of L-Arg showed
      moderately higher inflammatory and fibrosis colonic scores than the D-Arg treated
      rats. There was no significant influence of L-Arg-free diets on the course of
      TNBS-induced colitis. However, L-Arg diet accelerated weight gain both pre- and
      post-TNBS. CONCLUSIONS: These results suggest that normal amounts of L-Arg in the
      diet are not harmful, whereas both absence of L-Arg or supplementation with high
      doses of this amino acid may be deleterious. In the former this might be due to a
      decrease of nitrogen retention in injured rats, whereas in the latter it may
      result from both nitric oxide-mediated tissue damage and collagen deposition.

PMID- 11534937
TI  - Inadequate fluid intakes in dysphagic acute stroke.
AB  - BACKGROUND AND AIMS: To investigate the fluid intakes of patients with dysphagic
      acute stroke and to evaluate the effect of disability, the ward speciality and
      the type of fluid given on oral intake. METHODS: Patients were prospectively
      recruited and randomly assigned to receive powder-thickened fluids or ready
      prepared pre-thickened fluids. Parenteral, enteral and oral fluid intakes, urine
      output, clinical sequelae and the frequency of requests for biochemical measures
      of hydration were recorded for a maximum of fourteen days. RESULTS: 24 patients
      with dysphagic acute stroke requiring thickened fluids were recruited from a
      large teaching hospital. Mean thickened fluid intake was 455 ml/d (SEM+/-70)
      resulting in the use of an extra 742 ml/d (+/-132) of supplementary fluids. This
      did not result in an adequate total intake due to insufficient volumes being
      given for too short a period. Patients not on specialist stroke units who
      received pre-thickened fluids drank almost 100% more than those on powder
      thickened fluids (P=0.04). CONCLUSIONS: Fluid intakes in this patient group are
      insufficient to achieve requirements. Hospital staff must ensure adequate fluid
      intakes in patients at risk of dehydration, which should include both an adequate
      prescription and provision of supplementary fluids. Pre-thickened drinks improve
      oral fluid intake in patients with dysphagic acute stroke on non-specialist
      wards.

PMID- 11534938
TI  - Use of a three-day estimated food record, a 72-hour recall and a food-frequency
      questionnaire for dietary assessment in a Mediterranean Spanish population.
AB  - AIM: To assess the validity and the short-term reproducibility of a semi
      quantitative, self-administrated food frequency questionnaire and a structured 72
      hour recall in a Mediterranean Spanish population. METHODS: 44 free-living
      volunteers participated in the study. Macronutrient, vitamin and mineral intake,
      recorded on the food frequency questionnaire and the structured 72-h recall were
      compared with intakes derived from a three-day food record (reference method).
      Validity of the dietary assessment methods was further assessed by comparing
      urinary nitrogen, plasma vitamin C, plasma beta-carotene and whole blood
      glutathione peroxidase activity levels with the corresponding nutrient intakes
      from the questionnaires. The food frequency questionnaire and the 72-h recall
      were administered twice to assess the short term reproducibility. RESULTS:
      Pearson's correlation coefficients between urinary nitrogen, plasma vitamin C,
      plasma beta-carotene and whole blood glutathione peroxidase activity levels and
      the reported nitrogen, vitamin C, beta-carotene and selenium intakes were 0.26,
      0.53, 0.17, 0.26 for the food frequency questionnaire; 0.41, 0.09, 0.34, 0.42 for
      the structured 72-h recall and 0.50, 0.54, 0.44, 0.38 for the three-day food
      record, respectively. The short term reproducibility of analysed nutrient intake
      showed average intra-class correlation coefficients of 0.91 and 0.69 for the food
      frequency questionnaire and the structured 72-h recall irrespectively.
      CONCLUSION: The food frequency questionnaire and the structured 72-h recall
      provide valid estimates of nutrient intake and could be used for dietary
      assessments.

PMID- 11534939
TI  - Influence of parenteral nutrition on postoperative recovery in an experimental
      model of peritonitis.
AB  - BACKGROUND AND AIMS: There seems to be no clear-cut indications for routine TPN
      support after major elective surgery. The present study was designed to
      investigate whether TPN could improve the results of standard surgical care for
      acute peritonitis (laparotomy plus antibiotics). ANIMALS AND METHODS: Peritonitis
      was induced in 48 New Zealand rabbits (day -2). On day 0, appendectomy and
      peritoneal lavage were performed, ceftriaxone (250 mg, i.m./24 h.) was started
      and animals were randomly assigned to receive regular fluids (RF), glucose-based
      TPN (G-TPN) or isocaloric fat-based TPN (F-TPN) for 6 days. MAIN OUTCOME
      MEASURES: Balance studies (days 1-3), s-albumin, thyroid hormones and urinary
      catecholamines were determined at various points of the experiment. At
      postmortem, wound infection, residual intra-abdominal infection and laparotomy
      wound breaking strength were recorded. RESULTS: Peritonitis produced a fall in
      weight, s-albumin and T3. At day 6, weight-loss was more pronounced in RF than in
      G-TPN or F-TPN (-7 vs 1.5 vs -1.2%;P=0.0001) but s-albumin and T3 concentrations
      were similar. Diuresis (377 vs 268 vs 269 mL/3 days; P=0.01) was higher and water
      balance lower (373 vs 511 vs 480 mL/3 days; P=0.01) in Group RF. Although the
      differences were not statistically significant (P<0.2), persistent infection and
      wound breaking strength were slightly worse in the pooled TPN groups compared
      with the RF group (19 vs 6% and 542 vs 701 g, respectively). CONCLUSIONS: TPN
      failed to improve relevant biochemical markers and clinical outcome after
      laparotomy for peritonitis.

PMID- 11534940
TI  - The reported use of dietary supplements (sip feeds) in hospitals in Wessex, UK.
AB  - AIMS: To assess the prevalence of the use of supplements (sip feeds) in district
      general, psychiatric and community hospitals in the former Wessex health region.
      METHOD: Cross sectional study of prevalence and determinants of supplement use in
      10 district general hospitals (covering medical, surgical, orthopaedic, and
      elderly specialities), 4 psychiatric hospitals and 3 community hospitals.
      RESULTS: Overall 14% of patients were being supplemented although the variation
      across hospitals and specialities was wide (0%-35%); elderly care patients within
      district hospitals were most likely to be supplemented (20%; range 12-35%). In
      34% of patients there was no documented reason as to why supplements were given.
      60% of patients were not weighed on admission; 70% did not have a weight history
      recorded and 83% did not have a current weight recorded. Documentation regarding
      supplement use appeared to be recorded in an unsystematic manner. CONCLUSIONS:
      Many patients were not being weighed on admission and appeared to have no
      documentation as to why supplements were given. Given the importance of
      malnutrition in hospital patients a more evidence based, objective approach to
      assessing nutritional requirements, intake and support may be beneficial.

PMID- 11534941
TI  - Muscle function in critically ill patients.
AB  - Endotoxemia and inflammation (cytokines) lead to an acute decrease of the muscle
      resting membrane potential, loss of the sodium-potassium gradient and to an
      increase in cytosolic Ca(2+) in critically ill intensive care unit patients. As a
      consequence, muscle (and nerve) contractility is reduced. As a consequence also,
      amino acid gradients are reduced, proteolysis is increased, the mitochondrial
      density is reduced to levels as low as 10% of normal within 2-3 days and cellular
      substrate metabolism is impaired. The author of this paper proposes that
      treatment modalities in clinical nutrition should primarily aim at improving
      muscle function and restoring muscle membrane potential and that these variables
      should be used as the primary outcome variables of clinical trials. Attempts to
      modify these measurements such that they can be used routinely in the ICU setting
      are ongoing in our group. Muscle protein and substrate metabolism can only be
      normalized when these primary variables have successfully been restored. The use
      of muscle relaxants may lead to a functional denervation of the muscle, to
      changes in the molecular structure of the myofibrils and may postpone a
      successfull recovery. LEARNING OBJECTIVES: Causes of muscle weakness and loss of
      contractility in ICU patients; Relation between loss of contractility and
      impairments in muscle metabolism; Muscle function as an endpoint variable for
      clinical nutrition interventions.

PMID- 11534942
TI  - Food and nutritional care in hospitals: how to prevent undernutrition--report and
      guidelines from the Council of Europe.
AB  - In 1999 the Council of Europe decided to collect information regarding Nutrition
      programmes in hospitals and for this purpose a network consisting of national
      experts from eight of the Partial Agreement member states was established. The
      aim was to review the current practice in Europe regarding hospital food
      provision, to highlight deficiencies and to issue guidelines to improve the
      nutritional care and support of hospitalized patients. Five major problems seemed
      to be common in this context: 1) lack of clearly defined responsibilities; 2)
      lack of sufficient education; 3) lack of influence of the patients; 4) lack of co
      operation among all staff groups; and 5) lack of involvement from the hospital
      management. To solve the problems highlighted, a combined 'team-effort' is needed
      from national authorities and all staff involved in the nutritional care and
      support, including hospital managers.

PMID- 11534943
TI  - Enteral nutrition by nasojejunal tube in hyperemesis gravidarum.
AB  - We describe two cases in which self-propelling, blind placed nasojejunal tubes
      were placed in severe hyperemesis gravidarum. This method provides an alternative
      to parenteral nutrition and to percutaneous endoscopic tubes, is well tolerated,
      cost effective and with a low rate of complication. Both mothers were given
      nutritional support at home, had normal subsequent pregnancies and normal babies.

PMID- 11534944
TI  - Use and abuse of albumin.

PMID- 11534945
TI  - Use of newborn Girardia tigrina (Girard, 1850) in acute toxicity tests.
AB  - Acute toxicity tests, exposing Girardia tigrina to potassium dichromate
      (K(2)Cr(2)O(7)), showed good reproducibility. The 95% confidence intervals among
      tests were 0.0262+/-0.0141 g for 48-h LC(50) (N=6) and 0.0129+/-0.0078 g for 96-h
      LC(50) (N=5). The 96-h LC(50) for G. tigrina was below that of oligochaetes and
      above that of cladocera.

PMID- 11534946
TI  - Accumulation of cyanobacterial hepatotoxins by Daphnia in some Egyptian
      irrigation canals.
AB  - In this study, microcosm experiments were run in the laboratory to test the
      possibility of feeding of Daphnia parvula on toxic Microcystis aeruginosa in some
      Egyptian irrigation canal at Sohag city. The results demonstrated that Daphnia
      has a priority of feeding on green algae and the diatom Melosira granulata over
      toxic M. aeruginosa during the first 10 days. Thereafter, when the green algae
      and diatom were depleted from the water, Daphnia started to feed on toxic
      Microcystis. This presumably indicates that Daphnia feeds facultatively on toxic
      cyanobacteria under the conditions of depletion of edible food. Additionally, the
      results indicated that Daphnia accumulates the Microcystis toxins "microcystins"
      in its body with a level of 1.78 microg toxin/25 daphnids. No release of toxin
      into the water was detected during the experimental period. This emphasizes that
      the disappearance of toxic Microcystis was due to the feeding by Daphnia, not to
      death or cell lysis. Such an accumulation of cyanobacterial hepatotoxins in the
      primary consumers (Daphnia) should be taken into consideration when zooplankton
      are used in the biomanipulation of toxic phytoplankton.

PMID- 11534947
TI  - Dose-dependent effects of dietary Pb and Zn on feeding and growth rates of the
      landsnail Helix engaddensis.
AB  - Dose-dependent effects of dietary lead and zinc on feeding and growth rates of
      adult Helix engaddensis snails were studied over a 1-month period followed by a 2
      week recovery period. Snails were fed on an artificial diet containing the
      following lead or zinc concentrations= 0, 20, 100, 500, 2500, and 12,500 microg/g
      dry food. At the end of the 6 weeks, mortality rate among snails fed on Pb
      contaminated diet was 18.3% (11/60) and the respective value for Zn-contaminated
      diet was 50% (30/60). Both metals significantly reduced growth and feeding rates.
      Snails were found to be sensitive to zinc but tolerant to lead. During the
      recovery period, snails fed on Zn-contaminated diet failed completely to feed or
      grow normally, whereas snails fed on Pb-contaminated diet showed signs of slow
      improvement in terms of feeding and growth rates. The NOEC and LOEC for lead were
      100 and 500 microg/g (-1), respectively, while the respective concentrations for
      zinc were 20 and 100 microg/g (-1).

PMID- 11534948
TI  - Water quality analysis of mixtures obtained from tannery waste effluents.
AB  - In this study, the mixing of waste solution obtained from chrome tanning process
      and waste solution derived from liming of bovine leather was investigated. The
      liming process of bovine leather was performed using calcium carbonate and sodium
      sulfide, and the tanning process was performed using alkaline chromium sulfate.
      The analyses of waste solutions and sediments formed during the mixing process
      include pH values, the concentration of sulfides, the concentration of
      chromium(III) oxide, and parameters such as chemical oxygen demand and
      biochemical oxygen demand. All measurements were carried out before and after the
      mixing process. Results indicate that the mixing of the corresponding waste
      solutions yields the mixture effluents that are ecologically acceptable.

PMID- 11534949
TI  - Effect of short-term exposure to chlorpyrifos on developmental parameters and
      biochemical biomarkers in Chironomus riparius Meigen.
AB  - Chironomus riparius Meigen were exposed to sediment spiked with 0, 0.01, 0.05,
      and 0.10 mg chlorpyrifos/kg dry sediment for 48 h as late third-instar larvae.
      Acetylcholinesterase activity, glutathione-S-transferase activity, burrowing
      behavior, emergence time, and adult dry weight were measured to determine which
      were the most sensitive biomarkers of exposure and effect for short-term
      sublethal exposures. There was a significant drop in acetylcholinesterase
      activity at the two highest concentrations, but no effect on glutathione-S
      transferase activity. Behavioral and life history biomarkers were sensitive only
      to the highest concentration of chlorpyrifos. The association of life history
      changes (female weight and male emergence times) with a significant inhibition of
      acetylcholinesterase activity suggests that this can be used as a biomarker of
      exposure and effect.

PMID- 11534950
TI  - Enchytraeids as indicator organisms for chemical stress in terrestrial
      ecosystems.
AB  - This review article surveys the available data on enchytraeid sensitivity toward
      chemical stress, and the effects of chemical stress on enchytraeid communities in
      terrestrial ecosystems. The factors affecting bioavailability of stressors to
      enchytraeids and the nature of direct and indirect effects that may occur are
      discussed, and the importance of laboratory tests and field studies for the
      evaluation of toxic effects is underlined. The existing data on specific types of
      stressors such as pesticides, metals, fertilizers, and industrial and domestic
      chemicals often show clear responses of enchytraeids, and in many cases
      interspecific differences in sensitivity are recorded. It is concluded that,
      although in several fields additional data are required, there are good
      perspectives for the use of enchytraeids as indicator organisms.

PMID- 11534951
TI  - Aliphatic hydrocarbons in birds of prey from Galicia (NW Spain).
AB  - Eleven aliphatic hydrocarbons, unresolved over resolved ratio (U/R), carbon
      preference index (CPI), pristane/C17 ratio, and totals were determined in six
      classes of tissues (heart, liver, intestine, muscle, lung, and kidney) of 10
      buzzards (Buteo buteo), 10 barn owls (Tyto alba), and five tawny owls (Strix
      aluco) from Galicia (NW Spain). Among individuals detected at quantifiable
      levels, in general, C18 was found to be the most abundant. Total aliphatic
      hydrocarbons were detected in 77% tissue samples. Phytane was detected in only
      three samples: intestine and muscle of two buzzards and lung of one barn owl.
      Pristane was found in 15% of total samples. Juveniles had higher concentrations
      than adults in the three species. Females had higher levels than males except for
      C32 and C36 in barn owl, C24 in tawny owls, and all hydrocarbons (except
      pristane) in buzzards. The highest concentrations of aliphatic hydrocarbons were
      detected in birds from La Coruna

PMID- 11534952
TI  - Direct and trophic contamination of the herbivorous carp Ctenopharyngodon idella
      by inorganic mercury and methylmercury.
AB  - A comparative analysis of inorganic mercury (Hg(II)) and methylmercury (MMHg)
      bioaccumulation by the herbivorous fish Ctenopharyngodon idella, via the direct
      and "direct+trophic" routes, was investigated experimentally. The direct
      contamination was based on fairly low exposure conditions (Hg(II), 300 ng small
      middle dotL(-1); MMHg, 30 ng small middle dotL(-1)), for 15 and 30 days. The
      trophic uptake was based on ingestion of macrophyte leaves (Elodea densa),
      previously exposed for 87 days to similar Hg concentrations. Results revealed
      high capacities of bioaccumulation in fish via the direct route, with
      accumulation factors of 1000 for Hg(II) and 13,000 for MMHg. Hg concentrations
      measured after direct+trophic contamination were very much greater than those
      measured after direct exposure, owing to considerable metal burdens accumulated
      in plants and to large biomasses ingested. Nevertheless, estimated trophic
      transfer rates were fairly low: 2% for Hg(II) and 13% for MMHg. MMHg
      determinations in elodea leaves and fish muscle samples reveal significant
      methylation and demethylation reactions.

PMID- 11534953
TI  - Copper and lead bioaccumulation by Acacia retinoides and Eucalyptus torquata in
      sites contaminated as a consequence of extensive ancient mining activities in
      Cyprus.
AB  - Aspects of the industrial archaeology of the northwestern part of the island of
      Cyprus are outlined. Wastes resultant from copper mining activities of
      approximately two millennia ago continue to exert an important influence on
      organisms. Detailed chemical analysis of two tree species growing on
      archaeologically important metalliferous spoil tips has indicated their ability
      to bioaccumulate heavy metals and sulfur primarily from the substratum; the
      bioaccumulation and biomagnification of lead and sulfur are particularly marked
      in both Acacia and Eucalyptus. The concentrations of elements in different parts
      of the two tree species are discussed and partitioning is noted together with the
      fact that while the pod of Acacia and the fruit capsule of Eucalyptus may have an
      enhanced metal loading, the values in the seeds are much reduced; the importance
      of this is discussed. The seeds of Acacia differ chemically from those of
      Eucalyptus. The importance of these plants as biomonitors of environmental
      quality is noted.

PMID- 11534954
TI  - Suitability of the trans/cis ratio of unsaturated fatty acids in Pseudomonas
      putida NCTC 10936 as an indicator of the acute toxicity of chemicals.
AB  - This study explored the suitability of using the trans/cis ratio of unsaturated
      fatty acids as an indicator of the acute toxicity of membrane active hazardous
      chemicals. The conversion of cis into trans fatty acids in Pseudomonas putida
      NCTC 10936 in response to 4-chlorophenol and temperature changes was compared
      with the results from another kind of toxicity test using the same organism,
      based on the sensitivity of its xylose oxidation-driven ATP synthesis to
      uncoupling. The response of both indicators is believed to be largely due to
      changes in the fluidity of the cytoplasmic membrane. However, the electron
      transport phosphorylation reacted faster and more sensitively to the fluidizing
      effect of 4-chlorophenol than the isomerization of unsaturated fatty acids.
      Therefore, measuring the trans/cis ratio does not provide as good early warning
      signals of acute toxicity as monitoring the response of the electron transport
      phosphorylation. If used as an indicator of chemostress, with Pseudomonas species
      as test organisms, the ratio should only be used in conjunction with other
      parameters reflecting the energetic state of the cells.

PMID- 11534955
TI  - Effects of methyl bromide fumigation on anhydrobiotic micrometazoans.
AB  - Anhydrobiotic organisms are well known for their resistance to extreme
      environmental conditions while in the inactive, ametabolic, state. This study
      confirms that this resistance also transfers to treatments with the fumigant
      methyl bromide. Live specimens of nematodes, rotifers, and tardigrades were found
      after 70 h of treatment with methyl bromide. Quantitative estimates of survival
      in the eutardigrade Richtersius coronifer revealed no difference between treated
      and untreated samples which had been kept dry for a short time. However, R.
      coronifer from samples collected 11 months before treatment had lower survival
      compared to samples collected shortly before the treatment. The fact that
      anhydrobiotic organisms escape treatments with biocides should be considered a
      serious problem, both for the food industry and from the perspective of human
      mediated spread of organisms.

PMID- 11534956
TI  - A study on geno- and immunotoxicological effects of subacute propoxur and
      pirimicarb exposure in rats.
AB  - A 28-day oral exposure with 8.51, 3.40, and 0.851 mg/kg propoxur (PR) and 4.67,
      1.87, and 0.467 mg/kg pirimicarb (PI) was performed in male Wistar rats, and the
      occurrence of numerical and structural chromosome aberrations and the changes in
      certain immune function parameters (plaque-forming cell (PFC) assay, delayed-type
      hypersensitivity reaction) and in some basic toxicological (body weight gain and
      weights of brain, thymus, lung, heart, liver, spleen, kidneys, adrenals, and
      popliteal lymph node) and hematological (white blood cells, red blood cells,
      hematocrit (Ht), mean cell volume of red blood cells (MCV) cell content of the
      femoral bone marrow) parameters were investigated. The high dose of PR increased
      the relative liver weight and the cell content of femoral bone marrow, and all
      three doses increased Ht and MCV. The applied doses of PI decreased the relative
      adrenal weight in a dose-dependent manner, and its highest dose increased the
      relative liver weight. Among the immune function parameters tested, PFC content
      of the spleen was decreased by high-dose PR and elevated by high-dose PI, whereas
      the maximum and the time course of the delayed-type hypersensitivity reaction
      showed no changes in this dose range. In the genotoxicological investigations
      only the high PR dose increased the number of numerical, but not the structural,
      chromosome aberrations. In addition to the changes in relative adrenal weight
      following PI treatment, the PFC assay showed the highest sensitivity for
      detection of the 4-week exposure with these carbamates. On the basis of our
      results, the immunotoxicological approach seems to have the same (PR) or higher
      (PI) sensitivity in early detection of the repeated low-dose exposure by these
      carbamates compared to the genotoxicological approach.

PMID- 11534957
TI  - Persistence and dissipation behavior of triazophos in canal water under Indian
      climatic conditions.
AB  - Laboratory studies were undertaken in canal water (pH 8.3) spiked with Hostathion
      (triazophos 40 EC) at the rates of 0.25 (T(1)) and 0.50 (T(2)) microg a.i. ml(-1)
      to investigate its persistence, dissipation, and degradation kinetics. Water
      samples collected on 0 (1h), 2, 5, 10, 20, 30, 45, 60, and 90 days after spiking
      were processed for residues of triazophos by GLC. In T(1) the dissipation was
      10.9, 19.1, 24.8, 40.4, 53.0, 73.0, and 83.0% in 2, 5, 10, 20, 30, 45, and 60
      days. Corresponding dissipation in T(2) was 9.2, 17.4, 21.2, 37.1, 50.6, 72.1,
      and 82.4%. In 90 days the dissipation was about 91% in both treatments. The half
      life values observed were 24.87 days in T(1) and 25.44 days in T(2). Kinetic
      studies revealed that dissipation of triazophos residues followed a first-order
      kinetics in both spiking levels.

PMID- 11534959
TI  - Children's respiratory health and daily particulate levels in 10 nonurban
      communities.
AB  - We conducted a study to assess the association between the acute respiratory
      health of children and the levels of particulates in communities near and away
      from active opencast coal mines. The study enrolled children aged 1-11 years from
      the general population of five socioeconomically matched pairs of nonurban
      communities in northern England. Diaries of respiratory events were collected for
      1405 children, and information was collected on the consultations of 2442
      children with family/general practitioners over the 6-week study periods during
      1996-1997, with concurrent monitoring of particulate levels. The associations
      found between daily PM(10) levels and respiratory symptoms were frequently small
      and positive and sometimes varied between communities. The magnitude of these
      associations were in line with those from previous studies, even though daily
      particulate levels were low, and the children were drawn from the general
      population, rather than from the population with respiratory problems. The
      associations among asthma reliever use, consultations with general practitioners,
      and daily particulate levels were of a similar strength but estimated less
      precisely. The strength of association between all respiratory health measures
      and particulate levels was similar in communities near and away from opencast
      coal mining sites.

PMID- 11534960
TI  - Blood lead levels among children aged 1 to 5 years in Wuxi City, China.
AB  - The objective of this study was to determine mean blood lead levels and
      prevalence of elevated blood lead levels among 1- to 5-year-old children in Wuxi
      City, China. By use of a representative cross-sectional survey that included
      measurements of capillary blood lead, 1117 children aged 1-5 years were examined
      from October through December, 1997. The geometric mean blood lead level for
      children 1-5 years of age in Wuxi City was 8.2 microg/dL (0.40 micromol/L); 27.3%
      had blood lead levels >or=10 microg/dL and 1.0% had blood lead levels >or=20
      microg/dL. Blood lead levels were significantly higher for males and for those
      living in industrial areas, particularly the Beitang, Mashan, and Xinqu
      districts. Residence in these districts and in the Jiaoqu industrialized district
      also increased the likelihood of an elevated blood lead level, with odds ratios
      ranging from 2.59 to 4.53. In conclusion, blood lead levels among Wuxi City
      children are high enough to be of concern, particularly in industrial areas.
      Further studies are needed to better define the extent of lead exposure among
      children in China. In addition, national standards for blood lead collection and
      measurement methods should be applied in China.

PMID- 11534961
TI  - The effects of elevated blood lead levels and succimer chelation therapy on
      physical growth in developing rhesus monkeys.
AB  - Seventy-two female rhesus monkeys were randomly assigned to three lead exposure
      conditions (none, birth to 1 year, birth to 2 years). In a completely crossed
      design, the lead-exposed and control monkeys were randomized to placebo or
      chelation therapy which began at 1 year of age. Dosing was conducted daily
      beginning on day 8 postpartum. The lead dose levels were adjusted biweekly to
      gradually elevate the blood lead level of each monkey to a target of 1.69-1.93
      micromol/L (35-40 microg/dL). Succimer (or placebo) was administered orally (30
      mg/kg/day for 5 days and 20 mg/kg/day for 14 additional days) for a total 19-day
      treatment regimen. There were two separate chelation regimes at 53 and 65 weeks
      of age. Succimer therapy in combination with lead abatement reduced blood lead
      levels significantly faster than lead abatement alone; however, that advantage
      disappeared once succimer therapy was discontinued. Weight, crown-rump length,
      and head circumference were measured regularly. Growth in weight, length, and
      head circumference did not vary significantly as a function of blood lead levels.
      Succimer chelation therapy did not significantly affect weight, length, or head
      circumference through 2 years of age.

PMID- 11534962
TI  - Biochemical and histopathological changes in serum creatinine and kidney induced
      by inhalation of Thimet (Phorate) in male Swiss albino mouse, Mus musculus.
AB  - This work was conducted to investigate the biochemical and histopathological
      changes in serum creatinine level and kidney of male Swiss albino mouse, Mus
      musculus, exposed to the recommended field dose of Thimet (20 kg ha(-1)). The
      animals were exposed to this dose in a whole-body inhalation chamber for 12 weeks
      and the biochemical and histopathological changes were studied in the 2nd, 4th,
      6th, 8th, 10th, and 12th weeks of exposure. Creatinine level of serum was
      measured by the Jaffe method, and histopathological lesions were studied by the
      hematoxylin-eosin staining method. A significant rise in creatinine level was
      observed from the 4th week of exposure until the end of the experiment. This rise
      suggests impairment of the glomerular function and tubular damage in the kidneys.
      These changes were confirmed by histopathological studies in the tubules. Kidney
      lesions were present throughout the experimental period. These consisted of mild
      to severe multifocal cloudy and hydropic degeneration with necrosis in the
      tubules, though the glomerular damage was not seen by light microscopy. After a
      30-day recovery period, the histopathological and biochemical changes were absent
      and normal patterns were restored.

PMID- 11534963
TI  - A side-by-side comparison of sampling methods for settled, indoor allergens.
AB  - Exposure to indoor allergens is associated with asthma, but there is no
      standardized sampling method for measuring allergens. We compared the association
      of measured allergen exposure and serum-specific IgE levels and the precision of
      three sampling methods (Cyclone, Mighty Mite, and Readivac II) to identify a
      standardized sampling method for indoor allergens. A random sample of 72
      children, 5 to 17 years old, with doctor-diagnosed asthma who lived in the same
      residence >or=2 years were enrolled. Composite, side by side floor samples were
      obtained with all three methods. Dust allergen concentrations and serum-specific
      IgE levels were measured for Der f I, Fel d I, and Bla g I. Mean allergen
      concentration did not differ significantly by sampling method. Cat allergen was
      significantly correlated with serum-specific IgE for Cyclone (P=0.003) and Mighty
      Mite (P=0.008), but only marginally for Readivac II (P=0.07). Dust mite allergen
      was significantly correlated with serum-specific IgE for Readivac II (P=0.02) and
      Cyclone (P=0.038), but not for Mighty Mite (P=0.12). Cockroach allergen was not
      correlated with serum-specific IgE for any sampling method. In multiple linear
      regression, cat allergen was associated with serum-specific IgE for Cyclone
      (P=0.007) and Mighty Mite (P=0.02), but not for Readivac II (P=0.06). In
      contrast, dust mite allergen was marginally associated with serum-specific IgE
      for Readivac II (P=0.07), but not for Mighty Mite (P=0.64) or Cyclone (P=0.27).
      The Cyclone and Mighty Mite were more precise than Readivac II for cat allergen,
      but there was no difference for dust mite allergen (P>0.05). No single method is
      superior for measurement of indoor allergens. In general, cat allergen collected
      with the Cyclone was a better predictor of serum-specific IgE levels to Fel d I,
      whereas dust mite allergen collected with the Readivac II was a better predictor
      of serum-specific IgE levels to Der f I.

PMID- 11534964
TI  - Cooking oil fume-induced cytokine expression and oxidative stress in human lung
      epithelial cells.
AB  - Epidemiological studies have shown an association between exposure to indoor air
      pollution from Chinese-style cooking and risk of lung cancer among Chinese
      females. Several toxic substances have been identified in cooking oil fumes (COF)
      collected from heated rapeseed oil. In this study, we examined the biological
      effects of COF on CL3 human lung epithelial cells. Exposure to 200 microg/ml COF
      significantly reduced cell growth within 4 days. In addition, we examined the
      effect of COF on TGFbeta1, TGFbeta2, IL-6, IL-8, and IFN-gamma gene expressions
      with the RT-PCR method. We found that TGFbeta1 mRNA levels increased after
      exposure to 200 microg/ml COF for 24 h. Similarly, exposure to 10 microM
      benzo[a]pyrene or 100 nM 12-O-tetradecanoylphorbol-13-acetate increased TGFbeta1
      mRNA levels at 24 h. The mRNA levels of TGFbeta2, IL-6, IL-8, and IFN-gamma did
      not increase after treatment with COF, benzo[a]pyrene, or 12-O
      tetradecanoylphorbol-13-acetate. COF-induced TGFbeta1 production was confirmed by
      quantification of TGFbeta1 in conditioned medium with enzyme-linked immunosorbent
      assay. Exposure to 200 microg/ml COF significantly increased TGFbeta1 secretion
      in a time-dependent and dose-dependent manner. It has been demonstrated that
      reactive oxygen intermediates induce TGFbeta1 gene expression. When CL3 cells
      were exposed to 200 microg/ml COF for 15 min, there was an increase in
      intracellular peroxide formation with the dichlorofluorescein method.
      Furthermore, treatment with 200 microg/ml COF for 12 h also significantly induced
      lipid peroxidation in CL3 cells. Our results show that exposure to COF inhibits
      cell growth, increases TGFbeta1 secretion, and induces oxidative stress in CL3
      lung epithelial cells. This suggests that TGFbeta1 and oxidative stress play a
      role in the biological effects of COF on lung epithelial cells.

PMID- 11534967
TI  - The interstitial nuclei of the human anterior hypothalamus: an investigation of
      variation with sex, sexual orientation, and HIV status.
AB  - The interstitial nuclei of the human anterior hypothalamus (INAH1-4) have been
      considered candidates for homology with the sexually dimorphic nucleus of the
      preoptic area of the rat. Volumetric sexual dimorphism has been described for
      three of these nuclei (INAH1-3), and INAH3 has been reported to be smaller in
      homosexual than heterosexual men. The current study measured the INAH in Nissl
      stained coronal sections in autopsy material from 34 presumed heterosexual men
      (24 HIV- and 10 HIV+), 34 presumed heterosexual women (25 HIV- and 9 HIV+), and
      14 HIV+ homosexual men. HIV status significantly influenced the volume of INAH1
      (8% larger in HIV+ heterosexual men and women relative to HIV- individuals), but
      no other INAH. INAH3 contained significantly more neurons and occupied a greater
      volume in presumed heterosexual males than females. No sex difference in volume
      was detected for any other INAH. No sexual variation in neuronal size or density
      was observed in any INAH. Although there was a trend for INAH3 to occupy a
      smaller volume in homosexual men than in heterosexual men, there was no
      difference in the number of neurons within the nucleus based on sexual
      orientation.

PMID- 11534968
TI  - Structural and functional sex differences in the human hypothalamus.
AB  - Sex differences in the brain may be the basis not only for sex differences in
      reproduction, gender identity (the feeling of being male or female), and sexual
      orientation (heterosexuality vs homosexuality), but also for the sex difference
      in prevalence of psychiatric and neurological diseases ( Swaab and Hofman, 1995
      ). In this brief article we discuss a few examples of structural and functional
      sex differences in the human brain.

PMID- 11534969
TI  - Sex differences in children's free drawings: a study on girls with congenital
      adrenal hyperplasia.
AB  - Sex differences are recognized in children's free drawings with respect to
      motifs, colors, figure compositions, and expression. Boys tend to draw mobile
      objects and mechanical objects with dark or cold colors and often use bird's-eye
      view composition when they draw pictures, whereas girls like to draw human motifs
      (especially girls and women), flowers, and butterflies with light and warm colors
      and tend to arrange motifs in a row on the ground. Analyses were made on the
      drawings of girls with congenital adrenal hyperplasia (CAH) and unaffected boys
      and girls, using masculine and feminine indexes. Sex difference in masculine and
      feminine indexes was clear in the drawings by unaffected boys and girls. Their
      drawings do not or mostly do not contain characteristics typical of the opposite
      sex. Compared with those of unaffected girls, the pictures of CAH girls more
      strongly showed masculine characteristics. The feminine index for the pictures of
      CAH girls was significantly lower than that for unaffected girls, while the
      masculine index for CAH girls was significantly higher than that for unaffected
      girls. Furthermore, the masculine index for CAH girls was not significantly
      different from that of unaffected boys. These results suggest that androgen
      exposure during fetal life may contribute to shaping masculine characteristics in
      children's free drawings.

PMID- 11534970
TI  - Fraternal birth order and the maternal immune hypothesis of male homosexuality.
AB  - In men, sexual orientation correlates with an individual's number of older
      brothers, each additional older brother increasing the odds of homosexuality by
      approximately 33%. It has been hypothesized that this fraternal birth order
      effect reflects the progressive immunization of some mothers to Y-linked minor
      histocompatibility antigens (H-Y antigens) by each succeeding male fetus and the
      concomitantly increasing effects of such maternal immunization on the future
      sexual orientation of each succeeding male fetus. According to this hypothesis,
      anti-H-Y antibodies produced by the mother pass through the placental barrier to
      the fetus and affect aspects of sexual differentiation in the fetal brain. This
      explanation is consistent with a variety of evidence, including the apparent
      irrelevance of older sisters to the sexual orientation of later born males, the
      probable involvement of H-Y antigen in the development of sex-typical traits, and
      the detrimental effects of immunization of female mice to H-Y antigen on the
      reproductive performance of subsequent male offspring. The maternal immune
      hypothesis might also explain the recent finding that heterosexual males with
      older brothers weigh less at birth than heterosexual males with older sisters and
      homosexual males with older brothers weigh even less than heterosexual males with
      older brothers.

PMID- 11534971
TI  - Prolactin receptors in the brain during pregnancy and lactation: implications for
      behavior.
AB  - Numerous studies have documented prolactin regulation of a variety of brain
      functions, including maternal behavior, regulation of oxytocin neurons,
      regulation of feeding and appetite, suppression of ACTH secretion in response to
      stress, and suppression of fertility. We have observed marked changes in
      expression of prolactin receptors in specific hypothalamic nuclei during
      pregnancy and lactation. This has important implications for neuronal functions
      regulated by prolactin. In light of the high circulating levels of prolactin
      during pregnancy and lactation and the increased expression of prolactin
      receptors in the hypothalamus, many of these functions may be enhanced or
      exaggerated in the maternal brain. The adaptations of the maternal brain allow
      the female to exhibit the appropriate behavior to feed and nurture her offspring,
      to adjust to the nutritional and metabolic demands of milk production, and to
      maintain appropriate hormone secretion to allow milk synthesis, secretion, and
      ejection. This review aims to summarize the evidence that prolactin plays a key
      role in regulating hypothalamic function during lactation and to discuss the
      hypothesis that the overall role of prolactin is to organize and coordinate this
      wide range of behavioral and neuroendocrine adaptations during pregnancy and
      lactation.

PMID- 11534972
TI  - Neuroendocrinology of maternal behavior in the rabbit.
AB  - Rabbit maternal behavior consists of building an underground nest of straw and
      body hair during late pregnancy and displaying, with circadian periodicity, a
      single 3-min nursing bout/day across lactation. Estrogen, androgen, progesterone,
      and prolactin regulate specific aspects of nest-building and promote the onset of
      maternal responsiveness. However, the maintenance of this behavior relies on
      stimuli from the litter: by preventing mother/young contact at parturition or
      during early lactation maternal responsiveness is altered or abolished. The brain
      areas controlling the expression of nest-building and nursing were investigated
      by implanting estradiol, locating the distribution of estrogen and prolactin
      receptors, quantifying the expression of immediate-early genes, and lesioning
      structures of the olfactory system. These studies revealed that: (a) estrogen
      receptor-alpha, alpha, present in the preoptic region, may mediate the
      stimulation of nest-building by estradiol; (b) prolactin binding sites, located
      mainly in periventricular structures, are more abundant in late pregnancy and
      early lactation; (c) the number of FOS-immunoreactive neurons increases in the
      lateral septum, but not in the mediobasal hypothalamus, following nursing; (d)
      the accessory olfactory bulb tonically inhibits the expression of maternal
      behavior because its removal promotes maternal responsiveness in virgins, which
      are otherwise unresponsive to daily pup exposure. In summary, rabbits rely on the
      same hormonal and extrahormonal factors that stimulate maternal behavior in other
      mammals, yet the way in which such factors promote elaborate nest-building and
      the unfailing display of circadian nursing is unique to rabbits and warrants
      future investigation.

PMID- 11534974
TI  - Hormonal changes in mammalian fathers.
AB  - Known and hypothesized relationships between steroid (estradiol, testosterone,
      and cortisol) and peptide (oxytocin, vasopressin, and prolactin) hormones and the
      expression of mammalian paternal behavior are reviewed. Emphasis is placed on
      newly emerging animal models, including nonhuman primates and men, with elaborate
      paternal behavior repertoires. Currently available data are broadly consistent
      with a working hypothesis that the expression of parental behavior will involve
      homologous neuroendocrine circuits in male and females. Understanding the
      neuroendocrinology of paternal behavior is an emerging research opportunity in
      behavioral neuroscience.

PMID- 11534973
TI  - Cellular mechanisms of social attachment.
AB  - Pharmacological studies in prairie voles have suggested that the neuropeptides
      oxytocin and vasopressin play important roles in behaviors associated with
      monogamy, including affiliation, paternal care, and pair bonding. Our laboratory
      has investigated the cellular and neuroendocrine mechanisms by which these
      peptides influence affiliative behavior and social attachment in prairie voles.
      Monogamous prairie voles have a higher density of oxytocin receptors in the
      nucleus accumbens than do nonmonogamous vole species; blockade of these receptors
      by site-specific injection of antagonist in the female prairie vole prevents
      partner preference formation. Prairie voles also have a higher density of
      vasopressin receptors in the ventral pallidal area, which is the major output of
      the nucleus accumbens, than montane voles. Both the nucleus accumbens and ventral
      pallidum are key relay nuclei in the brain circuits implicated in reward, such as
      the mesolimbic dopamine and opioid systems. Therefore, we hypothesize that
      oxytocin and vasopressin may be facilitating affiliation and social attachment in
      monogamous species by modulating these reward pathways.

PMID- 11534975
TI  - Genomic imprinting, maternal care, and brain evolution.

PMID- 11534976
TI  - Estradiol induces formation of dendritic spines in hippocampal neurons:
      functional correlates.
AB  - Dissociated cultured rat hippocampal pyramidal neurons respond to estradiol with
      a time-dependent, twofold increase in density of their dendritic spines. This
      effect is mediated by an estrogen receptor, probably of the alpha nuclear
      receptor type. In searching for the molecular mechanisms leading from the initial
      activation of the estrogen receptor to the final formation of new dendritic
      spines, we found that estradiol acts on GABAergic interneurons expressing the
      estrogen receptor by decreasing their inhibitory tone. In culture, this is
      assumed to cause a shift in the balance between excitation and inhibition toward
      enhanced excitation, overactivation of the pyramidal neurons, and subsequent
      formation of novel dendritic spines. The action of estradiol on spine formation
      is mediated by phosphorylation of cyclic AMP response element binding protein in
      the pyramidal neurons and is blocked when inhibition is enhanced by diazepam and
      when excitation is blocked by tetrodotoxin. Progesterone blocks the effect of
      estradiol on dendritic spines through its conversion to tetrahydroprogesterone,
      which enhances GABAergic inhibition. Subsequent to formation of novel dendritic
      spines, there is an increase in the density of glutamatergic receptors in the
      affected cells, an increase in the cellular calcium response to glutamate, and an
      increase in network synaptic activity among the cultured neurons.

PMID- 11534977
TI  - Seasonal activation and inactivation of song motor memories in wild canaries is
      not reflected in neuroanatomical changes of forebrain song areas.
AB  - Seasonal, testosterone-dependent changes in sexual behaviors are common in male
      vertebrates. In songbirds such seasonal changes occur in a learned behavior-
      singing. Domesticated male canaries (Serinus canaria) appear to lose song units
      (syllables) after the breeding season and learn new ones until the next breeding
      season. Here we demonstrate in a longitudinal field study of individual, free
      living nondomesticated (wild) canaries (S. canaria) a different mode of seasonal
      behavioral plasticity, seasonal activation, and inactivation of auditory-motor
      memories. The song repertoire composition of wild canaries changes seasonally:
      about 25% of the syllables are sung seasonally; the remainder occur year-round,
      despite seasonal changes in the temporal patterns of song. In the breeding
      season, males sing an increased number of fast frequency-modulated syllables,
      which are sexually attractive for females, in correlation with seasonally
      increased testosterone levels. About 50% of the syllables that were lost after
      one breeding season reappear in the following breeding season. Furthermore, some
      identical syllable sequences are reactivated on an annual basis. The seasonal
      plasticity in vocal behavior occurred despite the gross anatomical and
      ultrastructural stability of the forebrain song control areas HVc and RA that are
      involved in syllable motor control.

PMID- 11534978
TI  - Mechanisms of ovarian steroid regulation of norepinephrine receptor-mediated
      signal transduction in the hypothalamus: implications for female reproductive
      physiology.
AB  - In many mammalian species, the ovarian steroid hormones estradiol (E(2)) and
      progesterone (P) act in the hypothalamus and preoptic area to coordinate the
      timing of female sexual receptivity with ovulation. We study lordosis behavior,
      an important component of sexual receptivity in rats, and its regulation by E(2)
      and P as a model system for understanding how hormonal modulation of synaptic
      neurotransmission influences reproductive physiology and behavior. Our findings
      suggest that E(2) and P extensively regulate synaptic communication involving the
      catecholamine norepinephrine (NE) in the hypothalamus. Estrogen priming shifts
      the balance of postsynaptic NE receptor signaling in the hypothalamus and
      preoptic area away from beta-adrenergic activation of cAMP synthesis toward
      alpha(1)-adrenergic signaling pathways. Attenuation of beta-adrenergic signal
      transduction is achieved by receptor-G-protein uncoupling, apparently due to
      stable receptor phosphorylation. E(2) modification of alpha(1)-adrenergic
      signaling includes both increased expression of the alpha(1B)-adrenoceptor
      subtype and a dramatic, P-induced reconfiguration of the biochemical responses
      initiated by agonist activation of alpha(1)-adrenoceptors. Among these is the
      emergence of alpha(1)-adrenergic receptor coupling to cGMP synthesis. We also
      present evidence that estrogen promotes novel, functional interactions between
      insulin-like growth factor-1 (IGF-1) and alpha(1)-adrenergic receptor signaling
      in the hypothalamus and preoptic area. Thus, estrogen amplification of signaling
      mediated by alpha(1)-adrenoceptors is multifaceted, involving changes in gene
      expression (of the alpha(1B)-adrenoceptor), switching of receptor linkage to
      previously inactive intracellular pathways, and the promotion of cross talk
      between IGF-1 and NE receptors. We propose that this hormone-dependent remodeling
      of hypothalamic responses to NE maximizes reproductive success by coordinating
      the timing of the preovulatory release of gonadotropins with the period of
      behavioral receptivity in female rodents.

PMID- 11534979
TI  - The synaptic organization of VMH neurons that mediate the effects of estrogen on
      sexual behavior.
AB  - Estrogen acts in the hypothalamic ventromedial nucleus (VMH) of female rats to
      promote sexual behavior, as typified by the lordosis response. Morphological
      changes in the VMH, such as increased synaptic profiles and increased dendritic
      spines, suggest that estrogen may modulate behavior by altering VMH synaptic
      organization. To understand the significance of these changes, this laboratory
      has been investigating the functional classes of lordosis-relevant neurons and
      their local connectivity. A neurotropic virus, pseudorabies virus (PRV), was used
      to transneuronally label the CNS network that controls the lordosis-producing
      muscles. When PRV was placed in the lumbar epaxial muscles, it was sequentially
      detected in the lumbar ventral horn, the medullary reticular formation, the
      periaqueductal gray, and finally the VMH. Subsequent analysis showed that the
      population of VMH neurons that were initially infected with PRV largely resided
      beyond the cluster of estrogen receptor-containing neurons. In a separate study,
      VMH neurons were visualized with Lucifer yellow, and their morphology was
      analyzed using confocal microscopy. Such analysis confirmed that estrogen
      treatment increased dendritic spines in the VMH. The particular VMH neurons in
      this study did not express nuclear estrogen receptor, which suggests that
      estrogen can increase spine density indirectly. These results represent initial
      steps toward unraveling the local circuit that mediates estrogenic action on a
      specific reproductive behavior.

PMID- 11534980
TI  - Ligand-independent activation of progestin receptors in sexual receptivity.
AB  - Ovarian steroid hormones, estradiol and progesterone, regulate cellular functions
      in the central nervous system, resulting in the alterations in physiology and
      reproductive behavior. One means by which steroid hormones exert their neural
      effects on reproductive behavior is via their intracellular receptors functioning
      as ligand-dependent transcription factors. Studies from our laboratory in the
      past few years have shown that in addition to their cognate ligands,
      neurotransmitters like dopamine can activate intracellular steroid receptors in a
      ligand-independent manner. Using biochemical and molecular approaches we have
      demonstrated that the effects of neurotransmitter dopamine, on reproductive
      behavior in female rats and mice, occur by means of cross talk between membrane
      receptors for dopamine and intracellular progestin receptors (PRs). In this
      article, our studies on the integration of intracellular signaling pathways
      leading to the activation of PRs and its impact on modulation of reproductive
      behavior are summarized.

PMID- 11534981
TI  - Analysis of transient expression of estrogen receptor-alpha in newborn rat
      primary auditory cortex.
AB  - In the primary temporal cortex (Te1) of newborn rats, we detected transient
      expression of alpha-type estrogen receptor (ER alpha). Since they have a
      pyramidal-like shape, they are considered neurons. By immunohistochemistry we
      found that they were absolutely devoid of glial fibrillary acidic protein but
      some of them contained calretinin, a calcium binding protein. It is already known
      that neurons in layer V of the Te1 extend their projections to the contralateral
      side of the Te1, the ipsilateral inferior colliculus, or the ipsilateral medial
      geniculate nucleus. Thus, we applied a retrograde track tracer into those regions
      of newborn rats and examined the possible colocalization of ER alpha signals and
      the tracer in the same cells. So far no clear colocalization of both signals has
      been detected in cells in the Te1. Thus, the cells expressing ER alpha
      transiently are not projecting to the assumed regions, at least at the newborn
      age examined in the present experiment. The possibility exists that (1) they are
      not projection neurons but local interneurons, (2) even though they are
      projection neurons, they did not have any synaptic contacts with their target
      region(s), (3) they may die after they are attached to the target neurons.
      Further analyses are needed to clarify the biological roles of ER alpha expressed
      transiently in these neurons. On the other hand, no ER beta cells were detected
      in the same region of the brain under the same condition. Thus, this finding was
      limited to the ER alpha.

PMID- 11534982
TI  - Classical and nonclassical estrogen action in the developing midbrain.
AB  - There is widespread acceptance that estrogen is involved in various steps of
      cellular differentiation during brain development. In the past years, we have
      demonstrated such a developmental role for estrogen in the rodent midbrain.
      Precisely, estrogen affects midbrain dopamine neurons with respect to functional
      and morphological maturation. On the cellular level, estrogen may act classically
      by binding and activating its respective nuclear receptors, thereby controlling
      the transcription of target genes. On the other hand, many estrogen effects in
      the CNS are transmitted nonclassically by interactions with putative membrane
      receptors and by stimulating distinct intracellular signaling cascades. In the
      midbrain, classical and nonclassical estrogen signaling routes operate side by
      side to ensure the proper development of dopaminergic cells. In the present
      report, we detail some of the cellular and molecular events which are activated
      by estrogen and are thought to take part in the estrogen-mediated stimulation of
      dopamine neuron differentiation.

PMID- 11534983
TI  - Are there biological bases for a beneficial effect of estrogens in neural
      diseases?

PMID- 11534984
TI  - Steroid effects on the gene expression of peripheral myelin proteins.
AB  - The present article summarizes recent observations obtained in our laboratory
      which clearly indicate that sex steroids exert relevant effects on the peripheral
      nervous system. In particular, the following important points have emerged: (1)
      Steroids exert stimulatory actions on the synthesis of the proteins proper of the
      peripheral myelin (e.g., glycoprotein Po and peripheral myelin protein 22) in
      vivo and on the Schwann cells in culture; (2) in many cases the actions of
      hormonal steroids are not due to their native molecular forms but rather to their
      metabolites (e.g., dihydroprogesterone and tetrahydroprogesterone in the case of
      progesterone; dihydrotestosterone and 5 alpha-androstane-3 alpha,17 beta-diol in
      the case of testosterone); (3) the mechanism of action of the various steroidal
      molecules may involve both classical (progesterone and androgen receptors) and
      nonclassical steroid receptors (GABA(A) receptor); and finally, (4) the
      stimulatory action of steroid hormones on the proteins of the peripheral myelin
      might have clinical significance in cases in which the rebuilding of myelin is
      needed (e.g., aging, peripheral injury, demyelinating diseases, and diabetic
      neuropathy).

PMID- 11534985
TI  - Pregnenolone sulfate and aging of cognitive functions: behavioral, neurochemical,
      and morphological investigations.
AB  - Neurosteroids are a subclass of steroids that can be synthesized in the central
      nervous system independently of peripheral sources. Several neurosteroids
      influence cognitive functions. Indeed, in senescent animals we have previously
      demonstrated a significant correlation between the cerebral concentration of
      pregnenolone sulfate (PREG-S) and cognitive performance. Indeed, rats with memory
      impairments exhibited low PREG-S concentrations compared to animals with correct
      memory performance. Furthermore, these memory deficits can be reversed by
      intracerebral infusions of PREG-S. Neurotransmitter systems modulated by this
      neurosteroid were unknown until our recent report of an enhancement of
      acetylcholine (ACh) release in basolateral amygdala, cortex, and hippocampus
      induced by central administrations of PREG-S. Central ACh neurotransmission is
      involved in the regulation of memory processes and is affected in normal aging
      and in human neurodegenerative pathologies like Alzheimer's disease. ACh
      neurotransmission is also involved in the modulation of sleep-wakefulness cycle
      and relationships between paradoxical sleep and memory are well documented in the
      literature. PREG-S infused at the level of ACh cell bodies induces a dramatic
      increase of paradoxical sleep in young animals. Cognitive dysfunctions,
      particularly those observed in Alzheimer's disease, have also been related to
      alterations of cerebral plasticity. Among these mechanisms, neurogenesis has been
      recently studied. Preliminary data suggest that PREG-S central infusions
      dramatically increase neurogenesis. Taken together these data suggest that PREG-S
      can influence cognitive processes, particularly in senescent subjects, through a
      modulation of ACh neurotransmission associated with paradoxical sleep
      modifications; furthermore our recent data suggest a role for neurosteroids in
      the modulation of hippocampal neurogenesis.

PMID- 11534986
TI  - Regulation of neurosteroid biosynthesis in the frog diencephalon by GABA and
      endozepines.

PMID- 11534987
TI  - The role of neurosteroids and nongenomic effects of progestins in the ventral
      tegmental area in mediating sexual receptivity of rodents.
AB  - Progesterone (P(4)) in the ventromedial hypothalamus (VMH) and ventral tegmental
      (VTA) is important for facilitation of lordosis; however, P(4)'s actions in these
      brain areas are different. Using lordosis in rodents as in vivo experimental
      models, we have examined the effects progestins exert in the midbrain and
      hypothalamus. Localization and blocker studies indicate that P(4)'s actions in
      the VMH require intracellular progestin receptors (PRs) but in the VTA they do
      not. Progestins that have rapid, membrane effects, and/or are devoid of affinity
      for PRs, facilitate lordosis when applied to the VTA. Manipulation of GABA and/or
      GABA(A)/benzodiazepine receptor complexes (GBRs) in the VTA alter lordosis, which
      suggests that progestins may interact with GBRs to facilitate receptivity by
      enhancing the function of GABAergic neurons. Interfering with P(4)'s metabolism
      to 5 alpha-pregnan-3 alpha-ol-20-one (3 alpha,5 alpha-THP), the most effective
      endogenous positive modulator of GBRs, or the biosynthesis of the neurosteroid 3
      alpha,5 alpha-THP in the VTA attenuates female sexual behavior in rodents.
      Stimulation of mitochondrial benzodiazepine receptors (MBRs), which enhance
      neurosteroid production, by infusions of a MBR agonist to the VTA enhances
      lordosis. 3 alpha,5 alpha-THP is increased in the midbrain of mated > proestrous
      > diestrous rodents. These data suggest that 3 alpha,5 alpha-THP has a proximate
      modulatory role on lordosis. In summary, the actions of P(4) in the VTA are
      different from those in the VMH that involve PRs. In the VTA, P(4) may facilitate
      lordosis following metabolism to and/or biosynthesis of 3 alpha,5 alpha-THP,
      which may have subsequent actions at GBRs and/or MBRs to acutely modulate female
      sexual behavior in rodents.

PMID- 11534988
TI  - Neuroendocrine and behavioral implications of endocrine disrupting chemicals in
      quail.
AB  - Studies in our laboratory have focused on endocrine, neuroendocrine, and
      behavioral components of reproduction in the Japanese quail. These studies
      considered various stages in the life cycle, including embryonic development,
      sexual maturation, adult reproductive function, and aging. A major focus of our
      research has been the role of neuroendocrine systems that appear to synchronize
      both endocrine and behavioral responses. These studies provide the basis for our
      more recent research on the impact of endocrine disrupting chemicals (EDCs) on
      reproductive function in the Japanese quail. These endocrine active chemicals
      include pesticides, herbicides, industrial products, and plant phytoestrogens.
      Many of these chemicals appear to mimic vertebrate steroids, often by interacting
      with steroid receptors. However, most EDCs have relatively weak biological
      activity compared to native steroid hormones. Therefore, it becomes important to
      understand the mode and mechanism of action of classes of these chemicals and
      sensitive stages in the life history of various species. Precocial birds, such as
      the Japanese quail, are likely to be sensitive to EDC effects during embryonic
      development, because sexual differentiation occurs during this period.
      Accordingly, adult quail may be less impacted by EDC exposure. Because there are
      a great many data available on normal development and reproductive function in
      this species, the Japanese quail provides an excellent model for examining the
      effects of EDCs. Thus, we have begun studies using a Japanese quail model system
      to study the effects of EDCs on reproductive endocrine and behavioral responses.
      In this review, we have two goals: first, to provide a summary of reproductive
      development and sexual differentiation in intact Japanese quail embryos,
      including ontogenetic patterns in steroid hormones in the embryonic and maturing
      quail. Second, we discuss some recent data from experiments in our laboratory in
      which EDCs have been tested in Japanese quail. The Japanese quail provides an
      excellent avian model for testing EDCs because this species has well
      characterized reproductive endocrine and behavioral responses. Considerable
      research has been conducted in quail in which the effects of embryonic steroid
      exposure have been studied relative to reproductive behavior. Moreover,
      developmental processes have been studied extensively and include investigations
      of the reproductive axis, thyroid system, and stress and immune responses. We
      have conducted a number of studies, which have considered long-term
      neuroendocrine consequences as well as behavioral responses to steroids. Some of
      these studies have specifically tested the effects of embryonic steroid exposure
      on later reproductive function in a multigenerational context. A
      multigenerational exposure provides a basis for understanding potential exposure
      scenarios in the field. In addition, potential routes of exposure to EDCs for
      avian species are being considered, as well as differential effects due to stage
      of the life cycle at exposure to an EDC. The studies in our laboratory have used
      both diet and egg injection as modes of exposure for Japanese quail. In this way,
      birds were exposed to a specific dose of an EDC at a selected stage in
      development by injection. Alternatively, dietary exposure appears to be a primary
      route of exposure; therefore experimental exposure through the diet mimics
      potential field situations. Thus, experiments should consider a number of aspects
      of exposure when attempting to replicate field exposures to EDCs.

PMID- 11534989
TI  - Developmental effects of estrogenic agents on mice, fish, and frogs: a mini
      review.
AB  - Laboratory experiments have demonstrated that exposure of rodents to sex hormones
      during prenatal or early postnatal life can cause permanent and irreversible
      alterations of the endocrine and reproductive organs, such as ovary, fallopian
      tube, uterus, cervix, vagina, and mammary gland in females; and testis,
      epididymis, prostate, and seminal vesicle in males; as well as non reproductive
      organs including bones and muscle and immune and nervous systems in both sexes.
      Early development of Xenopus laevis into the tadpole and Fundulus heteroclitus
      goes through a rapid cell division, gastrulation, neurulation, and organogenesis
      within 1 week after fertilization. The developing embryo is very fragile and
      sensitive to estrogenic agents. Thus, these animals can be used as a suitable
      model for examining the effect of endocrine disruptors (hormonally active agents)
      on the development of aquatic living beings, which are most likely to be exposed
      to the compounds.

PMID- 11534990
TI  - Effects of prenatal exposure to low doses of diethylstilbestrol, o,p'DDT, and
      methoxychlor on postnatal growth and neurobehavioral development in male and
      female mice.
AB  - We examined effects of a wide range of doses of three man-made estrogenic
      chemicals during fetal life on neurobehavioral changes during early postnatal
      life in mice. Pregnant mice were fed a 4-log range of o,p'DDT, methoxychlor
      (MXC), and the drug diethystilbestrol (DES) from gestation days 11 to 17.
      Offspring were examined for changes in postnatal growth and the development of
      neuromuscular reflexes. Fetal exposure to the estrogenic chemicals altered the
      number of live pups per litter, the sex ratio of the litters, the anogenital
      distance of male and female offspring at birth (a bioassay for fetal androgen
      action), and the body weight of offspring at birth and during the first 5 days of
      postnatal life. In most cases, however, the dose-response relationships were
      complex (non-monotonic), with effects at the highest dose examined being opposite
      to effects seen at lower doses. The two markers of neurobehavioral development,
      righting and cliff avoidance reflexes, were not sensitive indicators of prenatal
      estrogen exposure. Only maternal exposure to the lowest MXC dose produced an
      increase in reactivity in righting and cliff avoidance tests in offspring.

PMID- 11534991
TI  - Male sexual polymorphism, alternative reproductive tactics, and androgens in
      combtooth blennies (pisces: blenniidae).
AB  - In species in which intense intermale competition for the access to females is
      present males of lower competitive ability may adopt alternative reproductive
      tactics (ART) to get access to mates. These ART translate in many cases into male
      sexual polymorphism, with individuals following distinctly different tactics.
      Usually two alternative male morphs can be recognized in species with ART: (1)
      bourgeois males that compete for access to mates invest in typically male
      behaviors, such as building elaborated nests or displaying ornaments; and (2)
      parasitic males that take advantage of the success of the bourgeois males in
      attracting females and attempt "sneaker" fertilizations (e.g., sneaker and
      satellite males). In combtooth blennies (Blenniidae) the co-occurrence of ART and
      male sexual polymorphism has been described for two temperate species: the
      peacock blenny, Salaria pavo, and the Azorean rock-pool blenny, Parablennius
      sanguinolentus parvicornis. Interestingly, while in the peacock blenny the
      alternative male morph adopts a sneaker tactic, in the rock-pool blenny parasitic
      males act as satellites to nest-holder males. Thus, this variation in the ART
      expressed in these two closely related species allows for a comparative study of
      the proximate and ultimate factors affecting the expression of the two ART. In
      this article we summarize the available information on androgen levels in
      bourgeois and parasitic males of natural populations of the two species and of
      recent studies on the effect of exogenous administration of androgens on tactic
      switching in parasitic males of the two species. The information is discussed
      within the frame of the relative plasticity hypothesis, which predicts that
      plastic alternative morphs should show differences in hormone levels and that the
      administration of sex steroids should be effective in promoting the switch from
      the parasitic to bourgeois tactic. The evidence is only partly consistent with
      this hypothesis. Alternatively, a social transduction hypothesis that better fits
      the available data on androgens and ART in teleost is proposed. It states that
      the observed differences in androgen levels between alternative morphs should not
      be interpreted as an organization vs activation effect of steroids, but rather as
      the limited vs lifelong responsiveness of the neuroendocrine axis to social
      regulation.

PMID- 11534992
TI  - Neuromuscular and endocrine control of an avian courtship behavior.
AB  - In many species of birds, males perform complex visual and acoustic courtship
      displays to attract and stimulate females. Some of these displays involve
      considerable use of the wings and legs, suggesting that they may be controlled by
      sexually dimorphic spinal motoneurons and their target muscles. Sex steroid
      hormones are known to organize and activate many sexually dimorphic phenotypes,
      so these neuromuscular systems may also be steroid sensitive. To test these
      ideas, we have begun studies of wild golden-collared manakins (Manacus
      vitellinus) in Central America. Males of this species establish a courtship arena
      in the forest, where they perform an elaborate dance that includes use of their
      wings to generate loud snapping sounds. Here we describe male golden-collared
      manakin courtship behavior, including the various "wingsnaps." We also review our
      studies, and those of others, showing sexually dimorphic properties of manakin
      wings, the wing musculature, and sex steroid accumulation in the spinal cord.
      These data suggest that manakins are useful models for evaluating steroid control
      of complex peripheral neuromuscular systems.

PMID- 11534993
TI  - Timing of breeding in variable environments: tropical birds as model systems.
AB  - Animals need to adjust reproductive decisions to environmental seasonality. In
      contrast to species from the well-studied temperate zones, little is known for
      tropical birds about the environmental cues that stimulate reproductive activity
      and the physiological mechanisms that regulate reproduction. I am investigating
      the environmental and endocrine mechanisms that underlie the timing of
      reproduction in spotted antbirds from the near-equatorial Panamanian rainforest
      and in small ground finches from the equatorial arid Galapagos islands. Spotted
      antbirds live in a fairly predictable seasonal environment and show regular
      changes in gonad sizes and some reproductive hormones. Despite the small annual
      variation in photoperiod close to the equator, these birds can measure slight
      photoperiodic increases and use it to initiate reproductive activity. Spotted
      antbirds also respond to seasonal changes in food availability, which allows them
      to flexibly adjust gonad growth to environmental conditions. Testosterone is
      involved in regulating song and aggressive behavior in these year-round
      territorial birds, although it can remain at low plasma levels throughout the
      year. In contrast, small ground finches exposed to a rather unpredictable climate
      on Galapagos appear to grow their gonads whenever heavy rains fall and have
      regressed gonads during other times of the year. The lack of a physiological
      preparation for the breeding season and their response to short-term cues related
      to rainfall indicate a striking flexibility in the regulation of breeding in
      small ground finches. I suggest that tropical birds can serve as model systems to
      study the physiological adaptations to different environments. Unraveling the
      neuroendocrine mechanisms behind the flexibility in reproductive timing will
      clarify whether differences found between temperate and tropical birds represent
      variations of the same basic mechanism or instead reflect a fundamental
      divergence in physiological control systems.

PMID- 11534994
TI  - Conditioning and sexual behavior: a review.
AB  - Sexual behavior is directed by a sophisticated interplay between steroid hormone
      actions in the brain that give rise to sexual arousability and experience with
      sexual reward that gives rise to expectations of competent sexual activity,
      sexual desire, arousal, and performance. Sexual experience allows animals to form
      instrumental associations between internal or external stimuli and behaviors that
      lead to different sexual rewards. Furthermore, Pavlovian associations between
      internal and external stimuli allow animals to predict sexual outcomes. These two
      types of learning build upon instinctual mechanisms to create distinctive, and
      seemingly "automated," patterns of sexual response. This article reviews the
      literature on conditioning and sexual behavior with a particular emphasis on
      incentive sequences of sexual behavior that move animals from distal to proximal
      with regard to sexual stimuli during appetitive phases of behavior and ultimately
      result in copulatory interaction and mating during consummatory phases of
      behavior. Accordingly, the role of learning in sexual excitement, in behaviors
      that bring about the opportunity to mate, in courtship and solicitation displays,
      in sexual arousal and copulatory behaviors, in sexual partner preferences, and
      the short- and long-term influence of copulatory experience on sexual and
      reproductive function is examined. Although hormone actions set the stage for
      sexual activity by generating the ability of animals to become sexually excited
      and aroused, it is each animal's unique experience with sexual behavior and
      sexual reward that molds the strength of responses made toward sexual incentives.

PMID- 11534995
TI  - Sex differences in the influence of mothers on the sociosexual preferences of
      their offspring.
AB  - The extent to which "nurture" as opposed to "nature" determines behavior and
      sociosexual preferences in mammalian species is controversial although most
      recent interest has focused on genetic determinants. We report here that if sheep
      and goats are cross-fostered at birth, but raised in mixed-species groups, their
      play and grooming behavior resembles that of their foster rather than genetic
      species. There are no sex differences in effects on these behaviors, and other
      species-specific behavior patterns such as aggression, browsing, climbing, and
      vocalizations are unaffected. In adulthood, cross-fostered males strongly prefer
      to socialize and mate with females of their foster mother's species, even if
      raised with a conspecific of their own species. Castration within 2 days of birth
      slightly reduces the level of this altered social preference but mating
      preference following short-term testosterone treatment is the same as for
      gonadally intact animals. Cross-fostered females also show significant preference
      for socializing with females and mating with males of their foster mother's
      species, although this effect is weaker than that in both gonadally intact and
      castrated males. When cross-fostered animals are placed in flocks containing
      members of only their genetic species for 3 years, male social and mating
      preferences for females of their mother's species remain virtually unaffected.
      Females change to display an exclusive mating preference for members of their
      genetic species in 1-2 years although they still retain some social interest in
      female members of their foster species. Thus, there are clear sex differences in
      the impact of the emotional bond between a mother and her offspring in these
      mammals. Effects on males are strongest and irreversibly maintained even after
      altering their social environment, whereas those on females are weaker and mating
      preferences are clearly adaptable in the face of altered social priorities. These
      sex differences are presumably caused by pre-, or early postnatal, organizational
      effects of sex hormones on the brain.

PMID- 11534996
TI  - Sex and context: hormones and primate sexual motivation.
AB  - Gonadal hormones regulate the ability to copulate in most mammalian species, but
      not in primates because copulatory ability has been emancipated from hormonal
      control. Instead, gonadal hormones primarily influence sexual motivation. This
      separation of mating ability from hormonally modulated mating interest allows
      social experience and context to powerfully influence the expression of sexual
      behavior in nonhuman primates, both developmentally and in adulthood. For
      example, male rhesus monkeys mount males and females equally as juveniles, but
      mount females almost exclusively as adults. Having ejaculated with a female
      better predicted this transition to female mounting partners than did increased
      pubertal testosterone (T). It is proposed that increased pubertal T stimulates
      male sexual motivation, increasing the male's probability of sexual experience
      with females, ultimately producing a sexual preference for females. Eliminating T
      in adulthood reduces male sexual motivation in both humans and rhesus monkeys,
      but does not eliminate the capacity to engage in sex. In male rhesus monkeys the
      effects of reduced androgens on sexual behavior vary with social status and
      sexual experience. Human sexual behavior also varies with hormonal state, social
      context, and cultural conventions. Ovarian hormones influence female sexual
      desire, but the specific sexual behaviors engaged in are affected by perceived
      pregnancy risk, suggesting that cognition plays an important role in human sexual
      behavior. How the physical capacity to mate became emancipated from hormonal
      regulation in primates is not understood. This emancipation, however, increases
      the importance of motivational systems and results in primate sexual behavior
      being strongly influenced by social context.

PMID- 11534997
TI  - Androgens, androgen receptors, and male gender role behavior.
AB  - Studies of genetic males with single gene mutations that impair testosterone
      formation or action and consequently prevent development of the normal male
      phenotype provide unique insight into the control of gender role behavior. 46,XY
      individuals with either of two autosomal recessive mutations [17 beta
      hydroxysteroid dehydrogenase 3 (17 beta-HSD3) deficiency or steroid 5 alpha
      reductase 2 (5 alpha-R2) deficiency] have a female phenotype at birth and are
      raised as females but frequently change gender role behavior to male after the
      expected time of puberty. In contrast, genetic males with mutations that impair
      profoundly the function of the androgen receptor are also raised as females and
      have consistent female behavior as adults. Furthermore, the rare men with
      mutations that impair estrogen synthesis or the estrogen receptor have male
      gender role behavior. These findings indicate that androgens are important
      determinants of gender role behavior (and probably of gender identity) and that
      this action is mediated by the androgen receptor and not the result of conversion
      of androgen to estrogen. The fact that all genetic males with 17 beta-HSD3 or 5
      alpha-R2 deficiency do not change gender role behavior indicates that other
      factors are also important determinants of this process.

PMID- 11534999
TI  - Dental size variation in the Atapuerca-SH Middle Pleistocene hominids.
AB  - The Middle Pleistocene Atapuerca-Sima de los Huesos (SH) site in Spain has
      yielded the largest sample of fossil hominids so far found from a single site and
      belonging to the same biological population. The SH dental sample includes a
      total of 452 permanent and deciduous teeth, representing a minimum of 27
      individuals. We present a study of the dental size variation in these hominids,
      based on the analysis of the mandibular permanent dentition: lateral incisors,
      n=29; canines, n=27; third premolars, n=30; fourth premolars, n=34; first molars,
      n=38; second molars, n=38. We have obtained the buccolingual diameter and the
      crown area (measured on occlusal photographs) of these teeth, and used the
      bootstrap method to assess the amount of variation in the SH sample compared with
      the variation of a modern human sample from the Museu Antropologico of the
      Universidade of Coimbra (Portugal). The SH hominids have, in general terms, a
      dental size variation higher than that of the modern human sample. The analysis
      is especially conclusive for the canines. Furthermore, we have estimated the
      degree of sexual dimorphism of the SH sample by obtaining male and female dental
      subsamples by means of sexing the large sample of SH mandibular specimens. We
      obtained the index of sexual dimorphism (ISD=male mean/female mean) and the
      values were compared with those obtained from the sexed modern human sample from
      Coimbra, and with data found in the literature concerning several recent human
      populations. In all tooth classes the ISD of the SH hominids was higher than that
      of modern humans, but the differences were generally modest, except for the
      canines, thus suggesting that canine size sexual dimorphism in Homo
      heidelbergensis was probably greater than that of modern humans. Since the
      approach of sexing fossil specimens has some obvious limitations, these results
      should be assessed with caution. Additional data from SH and other European
      Middle Pleistocene sites would be necessary to test this hypothesis.

PMID- 11534998
TI  - Homoplasy and the early hominid masticatory system: inferences from analyses of
      extant hominoids and papionins.
AB  - Early hominid masticatory characters are widely considered to be more prone to
      homoplasy than characters from other regions of the early hominid skull and
      therefore less reliable for phylogenetic reconstruction. This hypothesis has
      important implications for current reconstructions of early hominid phylogeny,
      but it has never been tested. In this paper we evaluate the likely veracity of
      the hypothesis using craniometric data from extant primate groups for which
      reliable consensus molecular phylogenies are available. Datasets representing the
      extant large-bodied hominoid genera and the extant papionin genera were compiled
      from standard measurements. The data were adjusted to minimise the confounding
      effects of body size, and then converted into discrete character states using
      divergence coding. Each dataset was divided into four regional character groups:
      (1) palate and upper dentition, (2) mandible and lower dentition, (3) face and
      (4) cranial vault and base. Thereafter, the regional character groups were
      analysed using cladistic methods and the resulting phylogenetic hypotheses judged
      against the consensus molecular phylogenies for the hominoids and papionins. The
      analyses indicated that the regions dominated by masticatory characters-the
      palate and upper dentition, and the mandible and lower dentition-are no less
      reliable for phylogenetic reconstruction than the other regions of the skull. The
      four regions were equally affected by homoplasy and were, therefore, equally
      unreliable for phylogenetic reconstruction. This finding challenges the recent
      suggestion that Paranthropus is polyphyletic, which is based on the assumption
      that masticatory characters are especially prone to homoplasy. Our finding also
      suggests that, contrary to current practice, there is no a priori reason to de
      emphasise the phylogenetic significance of the masticatory similarities between
      Homo rudolfensis and the australopiths. The corollary of this is that H.
      rudolfensis is unlikely to be a member of the Homo clade and should therefore be
      allocated to another genus.

PMID- 11535000
TI  - Taphonomy of the fossil hominid bones from the Acheulean site of Castel di Guido
      near Rome, Italy.
AB  - Castel di Guido near Rome is one of the few open air Middle Pleistocene European
      sites that has yielded hominid skeletal remains associated with fossil fauna and
      Acheulean implements. The fossil hominid bones include two femoral shafts,
      respectively designated Castel di Guido-1 (CdG-1) and CdG-2, an occipital
      fragment (CdG-3), a right maxilla lacking teeth (CdG-4), a portion of right
      parietal (CdG-5), a right temporal (CdG-6), and a fragment of left parietal vault
      (CdG-7). CdG-1 through CdG-4 were collected in 1979-1982 on the surface, together
      with fossil fauna, where ploughing incised fossiliferous tuffaceous sands.
      Excavations conducted in the same area from 1980 to 1990 led to the discovery of
      CdG-5, CdG-6 and CdG-7 within the tuffaceous sands, which were shown to overlay a
      bone-bearing paleosurface, with abundant evidence of hominid activities. The
      Castel di Guido hominid assemblage poses intriguing taphonomic questions. The
      analysis of the physical evidence offered by the bone surfaces, reported in the
      present study, indicates that the hominid skeletal remains were heavily
      fragmented before fossilization and exposed to carnivores and rodents, as well as
      to trampling and/or friction in abrasive sediment. Although definitive
      conclusions cannot be reached on the basis of the available evidence, it is
      possible that clusters of incisions localized on specific regions of the Castel
      di Guido fossil hominid bones might reflect deliberate human manipulations.

PMID- 11535001
TI  - The first discovery of a complete skeleton of a fossil orang-utan in a cave of
      the Hoa Binh Province, Vietnam.
AB  - Here we provide a description of the first complete adult fossil orang-utan
      skeleton from the Asian mainland. This specimen, and remains of a juvenile orang,
      were collected in a late Pleistocene cavern in the Hoa Binh Province of The
      Socialist Republic of Vietnam. The results confirm the suggestions by Hooijer
      (1948) Zool. Meded. Leiden29, 175-301 and later by Schwartz et al. (1995)
      Anthrop. Pap. Am. Mus. Nat. Hist.76, 1-24, that ancient orang-utans had bigger
      teeth than those of modern Pongo pygmaeus (P. p. pygmaeus and P. p. abelii),
      while the dental morphology is similar. Body proportions of the adult individual
      of Hoa Binh show a large skull with very large teeth but proportionally a small
      body. This individual is also singular in having high intermembral and brachial
      indices, in comparison with those of modern subspecies.

PMID- 11535002
TI  - Gerstmann-Straussler-Scheinker syndrome,fatal familial insomnia, and kuru: a
      review of these less common human transmissible spongiform encephalopathies.
AB  - Creutzfeldt-Jakob disease (CJD), Gerstmann-Straussler-Scheinker syndrome (GSS),
      fatal familial insomnia (FFI) and kuru constitute major human prion disease
      phenotypes. Each has been successfully transmitted in animal models and all are
      invariably fatal neurodegenerative disorders, with the brains of affected
      individuals harbouring variable amounts of an abnormal, protease-resistant form
      of the prion protein (PrPres), which is inextricably linked to pathogenesis and
      transmissibility. Classical sporadic CJD is the most common human transmissible
      spongiform encephalopathy (TSE), but recently the variant form (vCJD), first
      described in the UK in 1996, has drawn considerable attention. In contrast to
      sporadic CJD, FFI and GSS are almost invariably genetically determined TSEs,
      caused by a range of mutations within the open reading frame of the prion protein
      gene (PRNP) on chromosome 20. By definition, the nosologic term FFI is reserved
      for patients manifesting prominent insomnia, generally in combination with
      dysautonomia, myoclonus, and eventual dementia, with the predominant pathologic
      changes lying within the thalami and a specific underlying mutation in PRNP. GSS,
      however, encompasses a more diverse clinical spectrum ranging from progressive
      cerebellar ataxia or spastic paraparesis (both usually in combination with
      dementia), to isolated cognitive impairment resembling Alzheimer's disease.
      Additional extra-pyramidal features, which may respond to dopaminergic therapy
      can also be seen. Neuropathological findings are also relatively diverse, partly
      overlapping with those found in Alzheimer's disease, especially the presence of
      neurofibrillary tangles (NFTs). Although GSS and FFI in their classical forms are
      differentiable clinical profiles, such divisions may have no intrinsic biological
      validity given the considerable intra-familial clinico-pathological diversity so
      commonly seen. Kuru constitutes a horizontally transmitted prion disease, which
      after a lengthy incubation period, presents clinically as a progressive
      cerebellar ataxia associated with tremors. It has now almost disappeared since
      the cessation of ritualistic endocannibalism in the late 1950s but was previously
      exclusively endemic amongst the Fore linguistic group and neighbouring tribes in
      the Eastern Highlands of New Guinea. Uniform topographical central nervous system
      histopathology includes spongiform change and neuronal loss, with amyloid (kuru)
      plaques in approximately 75% of cases.

PMID- 11535003
TI  - Brain injury: the pathophysiology of the first hours.'Talk and Die revisited'.
AB  - In the 25 years since the 'Talk and Die' paper there have been substantial
      advances in the management of patients with severe closed head injury. This paper
      discusses developments in understanding of primary and secondary injury. Current
      management focuses on preventing secondary brain injury. That this has been
      successful is illustrated by a fall in mortality in recent decades. Evidence
      based guidelines have set standards of management but they do not take into
      account variations between individuals, between regions of the brain and
      variations with time from injury. Various monitoring techniques such as
      transcranial doppler, jugular venous oxygen saturation and ICP waveform analysis
      attempt to set individual therapeutic endpoints and to target therapy
      appropriately. Primary injury is no longer seen as a single irreversible event
      occurring at the time of impact, but rather as a process initiated by the impact
      and evolving over subsequent hours and days. Experimental studies have identified
      agents which reduce the evolution of brain injury and improve outcome. An
      experimental model of brain injury developed by the Adelaide He ad Injury Group
      identifies diffuse axonal injury as a target for therapeutic manipulation.
      Magnesium has been shown in other studies to improve outcome after diffuse brain
      injury. This has now been linked with upregulation of beta amyloid precursor
      prote in. Although this and several other experimental therapies have shown great
      promise, they have not so far produced benefit in large clinical studies.
      Avoiding secondary insults will remain the goal of management for the foreseeable
      future. Halting the evolution of the primary injury remains a highly sought after
      goal. Although elusive so far, it is likely to be the next major advance in
      clinical care.

PMID- 11535004
TI  - CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and
      Leucoencephalopathy): an Australian perspective.
AB  - Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and
      Leucoencephalopathy (CADASIL) is a recently described cause of stroke or stroke
      like episodes. It is caused by mutations in the Notch3 gene on chromosome 19p. We
      sought to demonstrate mutations of the Notch3 gene in Australian patients
      suspected of having CADASIL. Patients from several families were referred to the
      study. A diagnosis was determined clinically and by neuroimaging. Those suspected
      of having CADASIL had sequencing of exons 3 and 4 of the Notch3 gene. Eight
      patients, two of whom were siblings, were suspected of having CADASIL. Five
      patients (including the siblings) had mutations. Because of strong clustering of
      Notch3 mutations in CADASIL, this has potential as a reliable test for the
      disease in Australian patients.

PMID- 11535005
TI  - Correlations between P300 components and regional cerebral blood flows.
AB  - To evaluate the diagnostic importance of event-related potential P300, the
      correlation between P300 and regional cerebral blood flow (rCBF) was investigated
      in various brain regions in patients with multiple cerebral infarction (16
      cases), chronic alcoholism (11 cases) and Alzheimer's disease (5 cases) and in
      seven healthy people. Cognitive function was also evaluated by mini-mental state
      examination. P300 latency and rCBF was measured by recording of evoked potentials
      using an oddball paradigm and stable xenon computed tomographic scanning,
      respectively. A significant (P<0.05) negative correlation between P300 and rCBF
      was observed in the thalamus in patients with multiple cerebral infarction and
      chronic alcoholism. In addition, a significant (P<0.01) negative correlation
      between P300 latency and the mini-mental state examination score and positive
      correlation between rCBF in the thalamus and the mini-mental state examination
      score were observed. These findings suggest that P300 latency is associated with
      rCBF in the thalamus and cognitive function.

PMID- 11535006
TI  - Vascular endothelial growth factor in chronic subdural haematomas.
AB  - OBJECTIVE: To elucidate molecular aspects of the mechanisms of expansion of
      chronic subdural haematomas (CSH), we examined the expression of two
      representative angiogenic factors, vascular endothelial growth factor (VEGF) and
      basic fibroblast growth factor (bFGF) in CSH. METHODS: We quantified VEGF and
      bFGF in haematoma fluid and serum of 20 patients with CSH using an enzyme-linked
      immunosorbent assay. Mean concentrations of VEGF in the haematoma fluid (10277
      pg/ml) and in serum, (355 pg/ml) were much greater than those of bFGF (haematoma,
      3.04 pg/ml; serum, 4.74 pg/ml). Surgical specimens, including dura and the outer
      membrane of the CSH were analysed by in situ hybridisation to detect VEGF mRNA.
      Macrophages and vascular endothelial cells in the outer membrane over expressed
      VEGF mRNA. CONCLUSIONS: Enhanced production of VEGF by macrophages and vascular
      endothelial cells in the outer membrane is thought to be pathogenetically
      important in CSH.

PMID- 11535007
TI  - Surgical decision-making on cerebral cavernous malformations.
AB  - This study is an attempt to clarify surgical decision-making on cerebral
      cavernous malformations based on the data available in the literature. Using a
      mathematical model, we calculated the morbidity-free survival curves of the
      patients harboring cerebral cavernous malformations. Using these survival curves,
      we calculated the morbidity-free life expectancies of the patients at certain age
      undergoing either natural course or surgery. For superficially located lesions,
      permissible surgical risks were very small ranging from 0.4 to 2.8 percent of
      combined morbidity and mortality. The surgical gain of morbidity free life
      expectancy was also very small (0.0-1.1 years) irrespective of patient's age or
      eloquence of the location. For deep lesions, the permissible risk of surgery was
      very large, ranging from 64.1% for a 20-year-old and 31.4% for a 60-year-old
      patient. The gain of morbidity-free life expectancy was also large for younger
      patients (17-25 years for 20-year-old patients), but this gain rapidly decreased
      as the patient's age grew older, becoming 1.1 to 3.1 years for 60-year-old
      patients. Surgery seems to be justified for younger patients with deep lesions.
      There seems to be little indication for surgery of superficial lesions as far as
      the risk of bleeding is concerned.

PMID- 11535008
TI  - Levodopa responsive Parkinsonism in adults with Angelman Syndrome.
AB  - Two intellectually disabled adults with Angelman Syndrome are reported who
      developed intermittent episodes of a severe resting tremor, cogwheel rigidity and
      bradykinesia in their late teens. The Parkinsonism was not due to medications and
      there was a dramatic improvement with levodopa therapy. The association between
      Angelman Syndrome and Parkinsonism has not previously been described.

PMID- 11535009
TI  - Hepatitis C virus (HCV) infection as a risk factor for spontaneous intracerebral
      hemorrhage: hospital based case-control study.
AB  - Hepatitis C Virus (HCV) infection was investigated as a risk factor for
      intracerebral hemorrhage (ICH) by HCV antibody screening in 462 patients with ICH
      and 462 control patients with cerebral infarction matched by age and sex.
      Laboratory examinations of hemostatic parameters and cholesterol level were also
      performed in patients with ICH. HCV infection was significantly more frequent in
      patients with ICH than controls (8.7% vs 3.5%, P< 0.01). ICH patients with HCV
      infection had significantly higher L-alanine:2-oxoglutarate aminotransferase
      level (P< 0.001), lower cholesterol level (P< 0.05), lower platelet count (P<
      0.05), and longer prothrombin time (P< 0.01) than ICH patients without HCV
      infection, although most of these values were within the normal range. These
      results demonstrate that HCV infection is a risk factor for spontaneous ICH.
      Subclinical clotting disorder and/or vessel wall friability resulting from
      hypocholesteremia may be associated with ICH in patients with HCV infection.

PMID- 11535010
TI  - Preoperative and postoperative seizures in patients with astrocytic tumours:
      analysis of incidence and influencing factors.
AB  - To evaluate the incidence and influencing factors related to preoperative and
      postoperative seizures, a retrospective analysis was performed in 190 patients
      with astrocytic tumours. Preoperative seizures occurred in 50 (26%) patients and
      27 (54%) of the m had recurrent seizures. Late-onset seizures developed after
      craniotomy in 11 (8%) of 140 patients. Seizures at presentation were
      significantly correlated with age at diagnosis (P=0.0204) and pathological grade
      of tumour (P=0.0040). The patients aged less than 40 years had a high risk of
      seizures at presentation (odds ratio=3.076, P=0.0134). Postoperative seizures
      were significantly associated with the presence of preoperative seizures
      (P<0.0001), type or duration of preoperative seizures (P<0.0001, P<0.0001,
      respectively) and serum level of anticonvulsant drug (P=0.0068). However, only
      the presence of preoperative seizures had a potential for prediction of
      postoperative seizures when evaluated by logistic regression model (odds
      ratio=20.859, P=0.0001). Fifty-nine percent of patients with recurrent seizures
      and 64% of patients with late-onset seizures had seizures which occurred within 6
      months after craniotomy. Despite therapeutic anticonvulsant levels, most
      postoperative seizures were associated with tumour recurrence or haemorrhage.
      Postoperative seizures commonly occurred relatively soon after craniotomy and
      prophylactic anticonvulsants should be given. In patients with postoperative
      seizures, particularly in the presence of therapeutic anticonvulsant level, brain
      computed tomography should be performed to exclude tumour recurrence or
      haemorrhage.

PMID- 11535011
TI  - Mechanisms of peritumoural brain dysfunction: metabolic and neuroreceptor
      findings in striatal C6 glioma.
AB  - The aetiology of the peritumoural brain dysfunction that is rectified by steroids
      is unknown. To determine potential aspects of its pathophysiological basis we
      performed metabolic, histochemical and neuroreceptor studies in rodents with
      striatal C6 glioma. This model is known to cause focal neurobehavioural and
      electrophysiological dysfunction. The fully quantitative [(14)C]-2-deoxyglucose
      autoradiographic technique of measuring local cerebral metabolism of glucose
      (LCMRglu) showed raised LCMRglu (22-29%) in the pallidum, substantia nigra and
      endopeduncular nucleus. Acetylcholinesterase (AChE) histochemistry and a range of
      ligand binding studies for dopamine type 1 and 2, and serotonergic 5
      HT(2)receptors were negative in the tumour and normal in peritumoural brain. 5-HT
      uptake sites and strong peripheral benzodiazepine receptor expression were
      present in the tumour. There was extensive up-regulation of peripheral
      benzodiazepine receptor expression in the peritumoural brain. These studies show
      there is metabolic dysregulation in brain regions functionally connected to, but
      anatomically distant from the striatum. There is also a peritumoural region of up
      regulated receptors that have many, predominantly inhibitory, functions. The
      relationship of these findings to peritumoural brain dysfunction is discussed.

PMID- 11535012
TI  - Measurement of intracellular cytokines in MS patients treated with beta
      interferon and association of a beta-interferon induced exacerbation with
      increased expression of gamma-interferon by monocytes.
AB  - The effects that immunomodulatory agents such as beta-Interferon (IFN-beta) exert
      upon cytokine production in autoimmune disease such as multiple sclerosis remain
      incompletely understood. The recent development of techniques to directly assess
      cytokine production within peripheral blood leucocytes promises to advance this
      field. beta-Interferon treatment occasionally causes short-lived exacerbations of
      neurological dysfunction, often associated with systemic flu-like symptoms.
      Whereas these side effects usually occur and remit within the first few months of
      therapy, we have identified several patients who have developed symptoms many
      months after the onset of treatment. To begin to investigate the cause of these
      late onset exacerbations, we assessed the intracellular cytokine profiles of two
      patients, one stable on IFN-beta treatment and another experiencing side effects.
      The latter patient exhibited an increase in the percentage of monocytes that
      expressed g-Interferon after IFN-beta administration, whereas no such modulation
      was seen in the patient without side effects.

PMID- 11535014
TI  - Seizure frequency affects event-related potentials (P300) in epilepsy.
AB  - To analyse the effect of epilepsy an P300 event-related potentials we studied 27
      patients with idiopathic generalized epilepsy (IGE), 13 patients with temporal
      lobe epilepsy (TLE) and 60 normal controls. The prolongation of P300 latencies
      was highly cor related with increasing age in controls but not epileptic
      patients. The age-corrected P300 latency used in this study was actual P300
      latency-predicted P300 latency (predicted P300 (msec)=306.20+0.79 age, P=0.001,
      R2=0.32). By using ANOVA analysis, the age-corrected latencies of P300 were
      significantly longer in TLE patients (19.72+/-47.82 msec, mean+/-SD) than in IGE
      patients (10.97+/-36.97 msec) and controls (0.23+/-20.28 msec). Likewise,
      significantly prolonged P300 latencies were seen in the epileptic patients with a
      seizure frequency more than 400 times (37.21+/-47.50 msec). The multivariate
      adjusted odds ratio for those who had TLE was 10.97 (95% CI=3.99 - 30.14 ) in the
      prolonged latencies of P300 compared with that of IGE patients. The odds ratio of
      longer latencies of P300 was 7.43 (95% CI=2.75 - 20.08) among those who had a
      high seizure frequency (> or =400 times) compared with those who had a low
      seizure frequency. No interaction between TLE and high frequency of attacks was
      found. The age at onset of seizure and duration of illness was not associated
      with P300 latency prolongation. From the above results, we might infer that the
      seizure type of TLE and a high frequency of seizure are two major independent
      precipitate factors for abnormal latencies of P300 in the epileptic patients.

PMID- 11535013
TI  - Endoscopic transsphenoidal approach through a widened nasal cavity for pituitary
      lesions.
AB  - We operated upon 12 patients with macroadenoma and two with Rathke's cleft cyst
      using an endoscope through a nasal speculum. Pure endoscopic endonasal
      transsphenoiolal approach (TSA) was performed in nine patients and endoscope
      assisted microscopic endo nasal TSA in five. A thin-bladed nasal speculum was
      used to achieve a wide, almost midline, pathway without an incision at the septal
      mucosa. This made it possible to convert from the endoscopic to the microscopic
      approach and vice versa at any time during operation as the occasion demanded. In
      10 of the 12 patients with macroadenoma, adenomas were removed totally and did
      not recur during the mean follow-up period of 24 months. Two adenomas could not
      be removed totally due to their invasiveness. In two of five patients who
      underwent endoscope-assisted microscopic TSA for macroadenoma, the endoscope
      could visualise residual tumour at blind corners after microscopic tumor removal.
      Two patients with Rathke's cleft cyst did not show recurrence. No patient showed
      sinonasal or endocrinological complications. Versatile use of the endoscope
      through a widened nasal cavity using a nasal speculum is a promising tool for the
      treatment of pituitary lesions.

PMID- 11535015
TI  - Combined anterior and posterior instrumentation in severe fracture-dislocation of
      the lower cervical spine with help of navigation: a case report.
AB  - The authors report a case of severe fracture-dislocation of C6-C7 with dural and
      spinal cord damage causing quadriplegia. The patient was treated surgically with
      circumferential stabilisation. Intense spinal instrumentation with pedicle screw
      fixation in addition to anterior decompression and plate fixation was essential
      for restoring the original vertebral column. This technique of internal fixation
      provided a more rigid anchor, however the risk to the neurovascular structures
      could not be completely eliminated. Therefore, the combined anterior and
      posterior stabilisation assisted with a navigation system was a safer and
      reasonable surgical treatment for this patient with severe cervical injuries.

PMID- 11535016
TI  - Memory impairment and spatial disorientation following a left retrosplenial
      lesion.
AB  - We treated a patient in whom a left retrosplenial lesion resulted in memory
      impairment and spatial disorientation. A 31 year old, right handed man was
      admitted to our hospital after the sudden onset of headache. He was alert,
      attentive and cooperative, and showed no motor or sensory deficits. Although
      intelligence was preserved, memory was obviously deficient. The patient proceeded
      in wrong directions after he left his hospital room and subsequently his home.
      Neuroimaging revealed a subcortical hematoma in the left cingulate isthmus, while
      single-photon emission computed tomography demonstrated decreased perfusion in
      the splenium and left parietal lobe.

PMID- 11535017
TI  - Cerebellopontine angle meningioma with a high jugular bulb.
AB  - A cerebellopontine angle meningioma originating from the skull base over a high
      jugular bulb is quite rare. We report a case of a 68-year-old woman who had a
      right cerebellopontine angle meningioma with a prominent high jugular bulb. CT
      and MRI revealed a round tumour which attached to a bony prominence over the high
      jugular bulb. The apex of the jugular bulb was 3 mm higher than the floor of the
      internal auditory canal. The tumour was removed via a suboccipital retrosigmoid
      approach. The bony projection was drilled off carefully using a diamond drill;
      the jugular bulb became visible through the thinned bone. When a meningioma of
      this type is removed including bony changes, special attention is needed to avoid
      injury to the jugular bulb.

PMID- 11535018
TI  - Mesangial proliferative glomerulonephritis with deposits of anti-nicotinic
      acetylcholine receptor antibody in a patient with myasthenia gravis.
AB  - A patient with myasthenia gravis developed nephrotic syndrome 3 years after
      thymectomy. The kidney biopsy specimen revealed mesangial proliferative
      glomerulonephritis with immune deposits. The glomerular mesangial cells and
      tubular epithelial cells were sensitive to alpha-bungarotoxin (alpha-BT), a
      ligand for nicotinic acetylcholine receptor (nAChR), and the binding was
      inhibited by native alpha-BT, as well as other nAChR ligands, nicotine and d
      tubocurarine. In addition, FITC-alpha-BT-neuromuscular junction complexes could
      also bind to the mesangial cells, and preincubation with unlabeled nAChR
      inhibited the binding. These findings are consistent with the notion that both
      nAChR-like protein and anti-nAChR antibody are present in t he mesangial cells of
      the patient. Although the pathogenetic role of anti-nAChR antibody on the
      development of glomerulonephritis is unclear, the present observations provide an
      important insight into the autoimmune-mediated pathophysiological relationship
      between myasthenia gravis and mesangial proliferative glomerulonephritis.

PMID- 11535019
TI  - Treatment of a sphenoid sinus mucocele using an endoscope combined with a
      navigating system: a case report.
AB  - A sphenoid sinus mucocele extending into the middle cranial fossa and the
      pterygomaxillary fissure was decompressed using an endoscope in combination with
      a navigation system. A 59-year-old woman was admitted with a 3 month history of
      retro-ocular pain and right sided exophthalmos. To evaluate the cystic lesion, a
      fibreoptic endoscope was inserted into the cyst through an erosive defect in the
      temporal bone. The histopathological appearance of cyst wall tissue confirmed the
      diagnosis of mucocele. After 4 months, the mucocele had refilled and the
      exophthalmos had recurred. At reoperation, the cyst was fenestrated using a rigid
      endoscope combined with a navigation system inserted via a sublabial
      transmaxillary approach. The proper site of cyst fenestration was precisely
      determined using the navigation system, permitting complete evacuation of this
      large lesion with minimal invasiveness.

PMID- 11535020
TI  - Intense and recurrent deja vu experiences related to amantadine and
      phenylpropanolamine in a healthy male.
AB  - We report a case of a 39-year-old caucasian healthy male physician who developed
      intense and recurrent deja vu experiences within 24h of initiating concomitant
      amantadine-phenylpropanolamine treatment against influenza. Deja vu experiences
      terminated on discontinuation of medication. Findings in temporal epilepsy
      suggest that mesial temporal structures, including hippocampus, are related to
      paramnesic symptoms. On the other hand, previous case reports have confirmed that
      both amantadine and phenylpropanolamine alone, and particularly in combination,
      can induce psychotic symptoms due to their dopaminergic activity. The authors
      suggest that deja vu experiences may be provoked by increased dopamine activity
      in mesial temporal structures of the brain.

PMID- 11535021
TI  - Intraaneurysmal embolization of an unruptured basilar tip aneurysm associated
      with moyamoya disease.
AB  - We describe a patient with moyamoya disease associated with an unruptured basilar
      tip aneurysm which was treated by endovascular embolization using Guglielmi
      detachable coils (GDCs). A 53-year-old man presented with left hemiparesis
      persisting for 3 mon ths before admission. Cerebral angiography revealed
      occlusion of the bilateral middle cerebral arteries and the left anterior
      cerebral artery, stenosis of the right anterior cerebral artery, and basal
      moyamoya vessels. In addition, a saccular small aneurysm was seen at the top of
      the basilar artery. The aneurysm was completely embolized by intraaneurysmal
      GDCs. Direct surgical clipping is often selected for the treatment of posterior
      fossa aneurysms in moyamoya disease. However, complete clipping is usually
      difficult due to the difficulties in operative technique associated with moyamoya
      disease. We suggest that the endovascular treatment using GDCs is comparatively
      safe and effective for the treatment of surgically difficult aneurysms in
      patients with moyamoya disease.

PMID- 11535023
TI  - Odontogenic subperiosteal abscess of orbit: a case report.
AB  - Subperiosteal abscess of orbit is an uncommon but serious complication of orbital
      infection. We report a case of a 78 year old gentleman who presented with
      bilateral periorbital oedema and proptosis. Computerised tomography of orbit
      revealed bilateral dilated superior ophthalmic veins. Bilateral carotid-cavernous
      fistula was initially suspected. Serial imaging showed an increasing bilateral
      subperiosteal lesion of the orbit. Fine needle aspiration confirmed subperiosteal
      abscess. A high level of awareness is necessary in diagnosing subperiosteal
      abscess.

PMID- 11535022
TI  - Pharyngeal perforation and spontaneous extrusion of the cervical graft with its
      fixation device: a late complication of C2-C3 fusion via anterior approach.
AB  - Stabilisation of the fracture-dislocation of the cervical spine is achieved
      effectively by anterior or posterior or combined methods with attendant short and
      long term benefits, risks and complications associated with each procedure.
      Recently anterior methods have gained wider acceptance. A variety of preoperative
      and postoperative complications associated with anterior cervical fusion are well
      recognised. However, the delayed pharyngeal or oesophageal perforation is a rare,
      serious and life threatening complication of an anterior cervical internal
      fusion.The authors report a case of delayed pharyngeal perforation and
      spontaneous extrusion of the C2-C3 graft with its fixation device. After coughing
      out the entire gamet of the graft with the fixation pin, the patient was relieved
      of excruciating pain and dysphagia and had no significant morbidity thereafter
      over a 12-year follow up period. Relevant aspects are discussed with a review of
      the pertinent literature.

PMID- 11535024
TI  - Diffuse white matter changes caused by dural arteriovenous fistula.
AB  - We present two patients with progressive dementia who showed diffuse white matter
      changes on magnetic resonance imaging (MRI) associated with dural arteriovenous
      fistula (DAVF) involving the transverse-sigmoid sinuses. Angiography of both
      patients revealed that DAVF was associated with multiple occlusive changes in the
      dural venous sinus. The associated occlusive changes isolated the straight sinus
      and the DAVF from the other venous sinuses, and concentrated the drainage of the
      DAVF in the straight sinus. We postulate that the venous hypertension of the
      straight sinus resulted in the venous ischemia of the white matter, diffuse white
      matter changes on MRI, and progressive neurological signs including dementia.
      Treatment of the DAVF reversed white matter changes and neurological signs.
      Associated with the venous sinus occlusions, the DAVF caused dementia with
      diffuse white matter changes due to the venous ischemia.

PMID- 11535026
TI  - Have the triptans fulfilled their promise?

PMID- 11535025
TI  - Have the triptans fulfilled their promise?

PMID- 11535027
TI  - Have the triptans fulfilled their promise?

PMID- 11535028
TI  - Medical Indemnity crisis worsens further.

PMID- 11535030
TI  - Nucleotide polymorphism in microcin V plasmids.
AB  - DNA sequence polymorphism was determined for the microcin V gene cluster encoded
      on the microcin V plasmids of 12 natural isolates of Escherichia coli. These
      microcin V gene clusters are similar in DNA sequence, with only 10 of the 683 bp
      polymorphic. Further, the levels and patterns of microcin V gene cluster
      polymorphism differ from those of a chromosomal region, trpORF2, sequenced from
      each of the host isolates. These contrasting levels and patterns of polymorphism
      suggest that the microcin V gene cluster has experienced an evolutionary history
      different from that of the host.

PMID- 11535031
TI  - ISMh2, a novel insertion sequence-like element associated with nifA from
      Mesorhizobium huakuii.
AB  - Sequence analysis of the nifA gene, including its 5' flanking region, of
      Mesorhizobium huakuii revealed the presence of a novel IS-like element called
      ISMh2. It is 828 bp in length and possesses two imperfect terminal inverted
      repeats of 14 bp with only one mismatch. The putative transposase encoded by
      ISMh2 is composed of 204 amino acids. In comparison with other insertion
      sequences ISMh2 likely belongs to the IS6 family. Multiple copies of ISMh2 were
      detected in the genome of M. huakuii 159 by Southern hybridization. RT-PCR
      analysis showed that nifA and ISMh2 cotranscribed. Attempts to detect the
      transposition ability of ISMh2 were unsuccessful.

PMID- 11535033
TI  - Features of the replicon of plasmid pAM10.6 of Pseudomonas fluorescens.
AB  - We describe features of the basic replicon of the 10.6-kb medium-copy-number
      plasmid pAM10.6. pAM10.6 was able to replicate in various Pseudomonas strains but
      was maintained in Escherichia coli only after the p15A origin of replication was
      inserted. Deletion analysis suggests that the pAM10.6 origin of replication is
      located in a 0.5-kb region that includes inverted and direct repeats upstream of
      the repA gene. RepA (204 aa) has a clear homology to plasmid replication proteins
      of some other gram-negative bacteria. The pas (plasmid addiction system) (genes
      encoded in the region of 480-bp) stabilizes plasmid maintenance in P. putida
      cells under nonselective conditions for at least 200 generations. A 3.75-kb PstI
      fragment of pAM10.6 joined to a Km(r) gene was shown to be a minimal plasmid unit
      maintained in P. putida as a monomer. Further deletions of this 3.75-kb fragment
      caused a drive to form stable head-to-tail dimeric plasmids in P. putida.

PMID- 11535032
TI  - New alkane-responsive expression vectors for Escherichia coli and pseudomonas.
AB  - We have developed Escherichia coli and Pseudomonas expression vectors based on
      the alkane-responsive Pseudomonas putida (oleovorans) GPo1 promoter PalkB. The
      expression vectors were tested in several E. coli strains, P. putida GPo12 and P.
      fluorescens KOB2Delta1 with catechol-2,3-dioxygenase (XylE). Induction factors
      ranged between 100 and 2700 for pKKPalk in E. coli and pCom8 in Pseudomonas
      strains, but were clearly lower for pCom8, pCom9, and pCom10 in E. coli. XylE
      expression levels of more than 10% of total cell protein were obtained for E.
      coli as well as for Pseudomonas strains.

PMID- 11535034
TI  - Development of small high-copy-number plasmid vectors for gene expression in
      Caulobacter crescentus.
AB  - Caulobacter crescentus is a bacterium with a distinctive life cycle and so it is
      studied as a cell development model. In addition, we have adapted this bacterium
      for recombinant protein production and display based on the crystalline surface
      protein (S)-layer and its C-terminal secretion signal. We report here the
      development of small, high-copy-number plasmid vectors and methods for producing
      an obligate expression host. The vectors are based on a narrow-host-range colE1
      replicon-based plasmid commonly used in Escherichia coli, to which was added the
      replication origin of the IncQ plasmid RSF1010. C. crescentus strains were
      modified to enable plasmid replication by introduction of the RSF1010 repBAC
      genes at the recA locus. The small (4.0-4.5 kb) plasmids were in high copy
      numbers in both C. crescentus and E. coli and amenable to rapid methods for
      plasmid isolation and DNA sequencing. The method for introducing repBAC is
      suitable for other C. crescentus strains or any bacterium with an adequately
      homologous recA gene. Application of the vector for protein expression, based on
      the type I secretion system of the S-layer protein, when compared to constructs
      in broad-host-range plasmids, resulted in reduced time and steps required from
      clone construction to recombinant protein recovery and increased protein yield.

PMID- 11535035
TI  - Analysis of a Bacteroides conjugative transposon using a novel "targeted capture"
      model system.
AB  - Large conjugative transposons (CTn's) are widespread among Bacteroides spp. and
      they are responsible for the high rates of Bacteroides tetracycline resistance,
      which is mediated by the tetQ gene. These elements are self-transmissible and
      conjugation can be induced up to 1000-fold by the addition of tetracycline to
      cultures prior to mating. In addition to self-transfer, the Bacteroides CTn's,
      such as CTn341, are able to mobilize unlinked genetic elements such as plasmids
      and mobilizable transposons in a tetracycline-inducible manner. To study the
      molecular properties of these unique elements, a vector was designed to capture
      CTn's for analysis in heterologous hosts. This plasmid, pFD670, consisted of the
      low-copy vector pWSK29, the RK2 oriT, an ermF gene, and a tetQ gene fragment
      containing the N-terminus and promoter. The vector was transferred into
      Bacteroides recipients containing CTn341 where it integrated into the tetQ gene
      by homologous recombination. This integrated construct then was transferred back
      into an Escherichia coli host where it replicated as a plasmid, pFD699, about 56
      kb in size. Further analysis showed that pFD699 could be transferred into
      Bacteroides hosts where it displayed the same tetracycline-inducible properties
      as the native CTn341. The captured element appeared to utilize a circular
      intermediate in both transfer and transposition, and integration into the
      chromosome seemed to be random. Hybridization studies with a range of Bacteroides
      CTn's encoding tetracycline resistance revealed a great deal of homology between
      most of the CTn's but there was much variation seen in the restriction patterns
      of these elements, suggesting great diversity among this group.

PMID- 11535036
TI  - A yeast expression vector and leucine selection in Escherichia coli to aid in the
      identification of novel genes.
AB  - The complete sequencing of the Saccharomyces cerevisiae genome provides a
      powerful tool for studying and elucidating essential cellular processes. To aid
      in the application of this resource to investigations into the molecular
      mechanisms of endoplasmic reticulum-associated protein degradation, a simple
      procedure was designed to generate a unique 2-microm LEU2-selectable yeast
      expression vector. Putative genes easily inserted into this vector are under
      control of the ADH1 promoter and transcription terminator sequences. Furthermore,
      a LEU2 selection in both yeast and Escherichia coli was used to allow the
      isolation of underrepresented plasmid from a pool of multiple vectors. Together,
      these advances in technology will be useful in the systematic analysis of novel
      yeast gene function.

PMID- 11535037
TI  - A cryptic plasmid from Pasteurella multocida has a predicted protein nearly
      identical to a transport protein from Actinobacillus actinomycetemcomitans.
AB  - Several plasmids from Pasteurella multocida have been shown to carry antibiotic
      resistance genes but no other genes possibly related to the organism's
      pathogenesis. We report here that sequence from the plasmid pLEM from a fowl
      isolate of P. multocida, strain 1059, contained one open reading frame that had
      significant identity with a predicted protein from pVT745, a plasmid that was
      isolated from a human oral isolate of Actinobacillus actinomycetemcomitans. This
      predicted protein had significant homology at the amino acid level to cation
      transport proteins.

PMID- 11535038
TI  - The plasmid-stabilizing ytl2 protein coats DNA in a sequence-independent manner.
AB  - Plasmids carrying the ytl2 gene from the large resident plasmid pSLT of
      Salmonella typhimurium were stabilized >10(5)-fold (compared to control ytl2-free
      plasmids) in S. typhimurium cells. Purified Ytl2 protein was localized in the
      cell cytosol and bound to DNA in a sequence-independent manner to form a high
      molecular-weight complex, suggesting cooperative binding to the DNA. A mutant
      ytl2 gene, with a modified C-terminus, did not mediate plasmid stabilization and
      the mutant Ytl2 protein did not bind cooperatively to DNA. In vivo, while a
      plasmid carrying the ytl2 gene was stabilized, another plasmid (lacking ytl2)
      coexisting in the same cell was not. This result suggests that the Ytl2 protein,
      newly synthesized in a transcription-translation complex, binds preferentially to
      DNA of the replicon which encodes it and that this binding initiates subsequent
      cooperative DNA coating by more Ytl2 molecules. Plasmid-encoded newly synthesized
      Ytl2 protein is thus unavailable to stabilize coresident plasmid DNA, which does
      not contain the ytl2 gene.

PMID- 11535039
TI  - Regulated ectopic expression and allelic-replacement mutagenesis as a method for
      gene essentiality testing in Staphylococcus aureus.
AB  - Conditional expression systems were utilized for the ectopic induction of
      essential genes in Staphylococcus aureus. Resulting strains were then subjected
      to allelic-replacement mutagenesis of the native allele under inducing conditions
      for expression of the ectopic copy of the gene. This strategy produced test
      strains whereby cellular viability was uniquely dependent on the presence of
      inducer and provided a direct and absolute confirmation of genetic essentiality
      for each locus. The procedure is particularly useful for genes that are difficult
      to analyze by conventional inactivation strategies due to either small size or
      complex genomic organization.

PMID- 11535040
TI  - Cues for plant cell differentiation and development.

PMID- 11535041
TI  - Choosing sides: establishment of polarity in zygotes of fucoid algae.
AB  - The acquisition and expression of polarity during early embryogenesis underlies
      developmental pattern. In many multicellular organisms an initial asymmetric
      division of the zygote is critical to the determination of different cell fates
      of the early embryonic cells. Zygotes of the marine fucoid algae are initially
      apolar and become polarized in response to external cues. This results in an
      initial asymmetric division of the zygote. Subsequent divisions occur in a highly
      ordered spatial and temporal pattern. A combination of cell biological and
      biochemical studies is providing new details, and some controversies concerning
      the mechanisms by which zygotic polarity is acquired and amplified. Here, we
      discuss some of the more recent studies that are allowing improved understanding
      of polarization in this system.

PMID- 11535042
TI  - Cell polarity in Arabidopsis trichomes.
AB  - Arabidopsis leaf trichomes are unicellular hairs that display a highly
      characteristic cell form that has a fixed orientation with respect to the basal
      distal leaf axis. The genetic, molecular and cell biological analysis of trichome
      morphogenesis reveal that various cellular processes need to be coordinated
      including regulation of the cell cycle, the cell size and the actin and tubulin
      cytoskeleton. Here we will focus on what is known about the establishment and
      maintenance of positional information during trichome formation.

PMID- 11535043
TI  - Function of plant shoot meristems.
AB  - Growth and development of higher plants is directed by the continuous activity of
      meristems, sites of sustained cell division. Organs are formed at the flanks of
      the shoot meristem, while the central region contains pluripotent stem cells. The
      developmental programme of the meristem is coordinated by interactions between
      cells in separate regions of meristems, and some of the genes involved have been
      studied. Transcription factors can be exchanged between meristem cell layers. The
      control of stem cell fate involves a ligand/receptor interaction that regulates
      the activity of a transcription factor, and genes expressed in organ primordia
      can feedback to restrict the activity of meristematic genes.

PMID- 11535044
TI  - Patterns and symmetries in leaf development.
AB  - The leaf is a coordinated mosaic of developmental domains, which are evident from
      leaf inception on the flanks of the apical meristem. The subdivision of the
      meristem into molecularly defined domains is regulated by the interactions of a
      number of gene products and by receptor kinase-mediated signals. The acquisition
      of symmetry axes in the emerging leaf is a process coordinated by hormones (such
      as auxin and cytokinins) and the expression of classes of genes (such as the knox
      and the ARP, as1/rs2/phan, genes). As with simple leaves, the architecture of
      compound leaves is defined by spatial/temporal gradients of regulatory gene
      functions: complexity results from the interplay between leaf differentiation
      processes and genes maintaining a partial level of indeterminacy in the
      developing primordium. Boundaries between regions with different molecular
      'addresses' are considered, in plants as in Drosophila, as organizing centres for
      lateral organ development.

PMID- 11535045
TI  - Developmental programmes in floral organ formation.
AB  - In contrast to animals, organogenesis in plants is continuous, allowing
      development in response to intrinsic and extrinsic signals. Organs arise from
      primordia formed on the flanks of meristems. The apical meristem produces
      primordia that acquire leaf identity, while floral meristems form primordia which
      develop into four organ types: sepals, petals, stamens and carpels. The
      production of mature organs involves two distinct processes, the initiation of
      organ primordia and the establishment of meristem, primordia and cell identities.
      Here we concentrate on floral organogenesis in Arabidopsis and examine the extent
      to which these processes utilize similar control mechanisms and regulatory
      molecules.

PMID- 11535046
TI  - Maternal control of seed development.
AB  - Maternal control of higher plant seed development is likely to involve female
      sporophytic as well as female gametophytic genes. While numerous female
      sporophytic mutants control the production of the ovule and the embryo sac true
      maternal effect mutations affecting embryo and endosperm development are rare in
      plants. A new class of female gametophytic mutants has been isolated that
      controls autonomous development of endosperm. Molecular analyses of these genes,
      known as FIS class genes, suggest that they repress downstream seed development
      genes by chromatin remodelling. Expression of the FIS genes in turn is modulated
      by parent specific expression or genomic imprinting which in turn is controlled
      by DNA methylation. Thus maternal control of seed development is a complex
      developmental event influenced by both genetic and epigenetic processes.

PMID- 11535047
TI  - Cell fate specification in the cereal endosperm.
AB  - While superficially simple, endosperm development is a complex, dynamic process.
      Cereal endosperms contain three major cell types: starchy endosperm, transfer
      cells and aleurone. The localized accumulation of the END1 transcript in the
      syncitial endosperm suggests that signals from the maternal placental tissue
      specify transfer cell type early. Aleurone fate is plastic and requires the
      continual input of positional cues to maintain cell identity. Starchy endosperm
      appears to be the default cell type. Mutant patterns suggest that a regulatory
      hierarchy integrates endosperm development. Requirements for gametic imprinting,
      maternal : paternal genome ratios and putative chromatin modeling factors
      indicate the importance of genomic control.

PMID- 11535048
TI  - Selective, high-affinity binding of ferric ions by glycine-extended gastrin(17).
AB  - Uptake of dietary iron is essential for replenishment of body stores. A role for
      the hormone gastrin in iron uptake as a chelator of ferric ions in the gastric
      lumen has been proposed previously [Baldwin, G. S. (1992) Med. Hypotheses 38, 70
      74]. Here, spectroscopic evidence of selective, high-affinity binding of ferric
      ions to progastrin-derived peptides in aqueous solution at low pH is provided.
      The maximum at 281 nm in the absorption spectrum of glycine-extended gastrin(17)
      at pH 4.0 increased (2.07 +/- 0.30)-fold in the presence of > or =2 equiv of
      ferric ions. Titration of glycine-extended gastrin(17) with ferric ions under
      stoichiometric conditions indicated that the stoichiometry of binding was 2.00 +/
      0.28 mol of Fe(3+)/mol of peptide. Fluorescence quenching experiments yielded
      values for the stoichiometry and apparent dissociation constant of the ferric ion
      glycine-extended gastrin(17) complex at pH 4.0 of 2.39 +/- 0.17 mol of Fe(3+)/mol
      and 0.62 +/- 0.19 microM, respectively. No interaction was detected with Co(2+),
      Cu(2+), Mn(2+), or Cr(3+). Electron paramagnetic resonance spectroscopy suggested
      that the iron ligands were either oxygen or sulfur atoms. Fluorescence quenching
      experiments with peptides derived from the glycine-extended gastrin(17) sequence
      indicated that one or more of the five glutamic acid residues were necessary for
      iron binding. The binding of ferric ions by glycine-extended gastrin(17) at low
      pH is consistent with a role for progastrin-derived peptides in iron uptake from
      the lumen of the gastrointestinal tract.

PMID- 11535049
TI  - Interrogation of heme pocket environment of mammalian peroxidases with diatomic
      ligands.
AB  - Recent studies demonstrate that myeloperoxidase (MPO), eosinophil peroxidase
      (EPO), and lactoperoxidase (LPO), homologous members of the mammalian peroxidase
      superfamily, can all serve as catalysts for generating nitric oxide- (nitrogen
      monoxide, NO) derived oxidants. These enzymes contain heme prosthetic groups that
      are ligated through a histidine nitrogen and use H(2)O(2) as the electron
      acceptor in the catalysis of oxidative reactions. Here we show that heme
      reduction of these peroxidases results in distinct electronic and/or
      conformational changes in their heme pockets using a combination of rapid
      kinetics measurements, optical absorbance, and diatomic ligand binding studies.
      Addition of reducing agent to each peroxidase at ground state [Fe(III) state]
      causes immediate buildup of the corresponding Fe(II) complexes. Spectral changes
      indicate that two LPO-Fe(II) species are present in solution at equilibrium.
      Analyses of stopped-flow traces collected when EPO, MPO, or LPO solutions rapidly
      mixed with NO were accurately fit by single-exponential functions. Plots of the
      apparent rate constants as a function of NO concentration for all Fe(III) and
      Fe(II) forms were linear with positive intercepts, consistent with NO binding to
      each form in a simple reversible one-step mechanism. Fe(II) forms of MPO and LPO,
      but not EPO, displayed significantly lower affinity toward NO compared to Fe(III)
      forms, suggesting that heme reduction causes a dramatic change in the heme pocket
      electronic environment that alters the affinity and/or accessibility of heme iron
      toward NO. Optical absorbance spectra indicate that CO binds to the Fe(II) forms
      of both LPO and EPO, but not with MPO, and generates their respective low-spin
      six-coordinate complexes. Kinetic analyses indicate that the binding of CO to EPO
      is monophasic while CO binding to LPO is biphasic. Collectively, these results
      illustrate for the first time functional differences in the heme pocket
      environments of Fe(II) forms of EPO, LPO, and MPO toward binding of diatomic
      ligands. Our results suggest that, upon reduction, the heme pocket of MPO
      collapses, LPO adopts two spectroscopically and kinetically distinguishable forms
      (one partially open and the other relatively closed), and EPO remains open.

PMID- 11535050
TI  - Mass spectrometric characterization of the human androgen receptor ligand-binding
      domain expressed in Escherichia coli.
AB  - The ligand-binding domain (LBD) of the human androgen receptor (hAR LBD),
      encompassing amino acids (AAs) 647-919, was expressed in Escherichia coli with an
      N-terminal polyhistidine tag (His(10)-hAR LBD) from a pET-16b vector. The
      overexpressed protein was initially insoluble in inclusion bodies, and was
      subsequently solubilized in 8 M guanidine hydrochloride (GdnHCl). The solubilized
      His(10)-hAR LBD was purified to apparent homogeneity by metal ion affinity
      chromatography in the presence of 6 M GdnHCl. The isolated protein migrated as a
      single band in sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS
      PAGE) with an apparent molecular mass of 33-34 kDa, as expected from the plasmid
      construct. Immunoblot analysis with C-terminal antibodies raised against a
      peptide corresponding to the last 19 AAs (AAs 901-919) of hAR revealed that the
      purified protein contained an immunoreactive epitope present within the AR and
      was of the appropriate size. Further characterization, using matrix-assisted
      laser desorption/ionization time-of-flight mass spectrometry (MALDI/TOF-MS),
      showed a single protein species of average mass 34 580 Da, confirming the size
      and purity of the purified His(10)-hAR LBD. Detailed tryptic peptide mapping
      analysis, using MALDI/TOF-MS, identified a total of eight peptides with a 30%
      coverage of the LBD, including the last tryptic peptide in the hAR sequence.
      These data confirm that the purified protein was the intact hAR LBD. AA
      sequencing of these tryptic peptides, using an HPLC-coupled electrospray
      ionization ion trap mass spectrometer (LC/ESI-ITMS and MS/MS), unambiguously
      confirmed that the peptides were from the hAR LBD. The purified His(10)-hAR LBD
      in 6 M GdnHCl could be renatured as determined by ligand-binding activity, with a
      similar equilibrium dissociation constant (K(d)) for [(3)H]-mibolerone and a
      similar steroid specificity to the AR isolated from rat ventral prostate.

PMID- 11535051
TI  - A comparative analysis of the immunological evolution of antibody 28B4.
AB  - In an effort to gain greater insight into the evolution of the redox active,
      catalytic antibody 28B4, the germline genes used by the mouse to generate this
      antibody were cloned and expressed, and the X-ray crystal structures of the
      unliganded and hapten-bound germline Fab of antibody 28B4 were determined.
      Comparison with the previously determined structures of the unliganded and hapten
      bound affinity-matured Fab [Hsieh-Wilson, L. C., Schultz, P. G., and Stevens, R.
      C. (1996) Proc. Natl. Acad. Sci. U.S.A. 93, 5363] shows that the germline
      antibody binds the p-nitrophenyl ring of hapten 3 in an orientation significantly
      different from that seen in the affinity-matured antibody, whereas the
      phosphonate moiety is bound in a similar mode by both antibodies. The affinity
      matured antibody 28B4 has more electrostatic and hydrophobic interactions with
      hapten 3 than the germline antibody and binds the hapten in a lock-and-key
      fashion. In contrast, significant conformational changes occur in the loops of
      CDR H3 and CDR L1 upon hapten binding to the germline antibody, consistent with
      the notion of structural plasticity in the germline antibody-combining site
      [Wedemayer, G. J., Patten, P. A., Wang, L. H., Schultz, P. G., and Stevens, R. C.
      (1997) Science 276, 1665]. The structural differences are reflected in the
      differential binding affinities of the germline Fab (K(d) = 25 microM) and 28B4
      Fab (K(d) = 37 nM) to hapten 3. Nine replacement mutations were found to
      accumulate in the affinity-matured antibody 28B4 compared to its germline
      precursor. The effects of each mutation on the binding affinity of the antibody
      to hapten 3 were characterized in detail in the contexts of both the germline and
      the affinity-matured antibodies. One of the mutations, Asp95(H)Trp, leads to a
      change in the orientation of the bound hapten, and its presence is a prerequisite
      for other somatic mutations to enhance the binding affinity of the germline
      antibody for hapten 3. Thus, the germline antibody of 28B4 acquired functionally
      important mutations in a stepwise manner, which fits into a multicycle mutation,
      affinity selection, and clonal expansion model for germline antibody evolution.
      Two other antibodies, 20-1 and NZA6, with very different antigen specificities
      were found to be highly homologous to the germline antibody of 28B4, consistent
      with the notion that certain germline variable-region gene combinations can give
      rise to polyspecific hapten binding sites [Romesberg, F. E., Spiller, B.,
      Schultz, P. G., and Stevens, R. C. (1998) Science 279, 1929]. The ultimate
      specificity of the polyspecific germline antibody appears to be defined by CDR H3
      variability and subsequent somatic mutation. Insights into the evolution of
      antibody-combining sites provided by this and other structural studies are
      discussed.

PMID- 11535053
TI  - Structural comparison of monomeric variants of the chemokine MIP-1beta having
      differing ability to bind the receptor CCR5.
AB  - MIP-1beta, a member of the chemokine family of proteins, tightly binds the
      receptor CCR5 as part of its natural function in the immune response, and in
      doing so also blocks the ability of many strains of HIV to enter the cell. The
      single most important MIP-1beta residue known to contribute to its interaction
      with the receptor is Phe13, which when mutated reduces the ability of MIP-1beta
      to bind to CCR5 by more than 1000-fold. To obtain a structural understanding of
      the dramatic effect of the absence of Phe13 in MIP-1beta, we used
      multidimensional heteronuclear NMR to determine the three-dimensional structure
      of the MIP-1beta F13A variant. We had previously shown that, unlike the wild-type
      protein which has been shown to be a tight dimer, the F13A mutant is monomeric
      even at high concentrations [Laurence, J. S., Blanpain, C., Burgner, J. W.,
      Parmentier, M., and LiWang, P. J. (2000) Biochemistry 39, 3401-3409], leading to
      significant changes in the NMR spectra of F13A and the wild-type protein. We have
      obtained a total of 940 structural restraints for MIP-1beta F13A, and have
      calculated a family of structures having a backbone rmsd from the average of 0.55
      A (residues 12-67). A structural comparison of the F13A mutant with a fully
      active monomeric variant, P8A, shows that despite some differences in the (1)H
      (15)N HSQC spectra the two are nearly identical in NOE distance restraints and in
      backbone conformation. A comparison of F13A with the wild-type protein shows
      largely the same fold, although differences exist in the N-terminal and loop
      regions for which the loss of the dimer in F13A can mainly account. A dynamics
      comparison confirms greater flexibility in F13A than in the wild-type protein in
      regions of dimer contact in the wild-type protein. In an analysis to determine if
      the large functional effect resulting from the loss of Phe13 is due to the local
      side chain change or due to more global structural changes, we conclude that
      local effects predominate. This suggests that a strategy for designing tight
      binding anti-CCR5 therapeutics should include a Phe-like component.

PMID- 11535052
TI  - Binding of NO and CO to the d(1) Heme of cd(1) nitrite reductase from Pseudomonas
      aeruginosa.
AB  - The cd(1) nitrite reductase, a key enzyme in bacterial denitrification, catalyzes
      the one-electron reduction of nitrite to nitric oxide. The enzyme contains two
      redox centers, a c-type heme and a unique d(1) heme, which is a
      dioxoisobacteriochlorin. Nitric oxide, generated by this enzymatic pathway, if
      not removed from the medium, can bind to the ferrous d(1) cofactor with extremely
      high affinity and inhibit enzyme activity. In this paper, we report the resonance
      Raman investigation of the properties of nitric oxide and carbon monoxide binding
      to the d(1) site of the reduced enzyme. The Fe-ligand (Fe-NO and Fe-CO)
      stretching vibrational frequencies are unusually high in comparison to those of
      other ferrous heme complexes. The frequencies of the Fe-NO and N-O stretching
      modes appear at 585 and 1626 cm(-1), respectively, in the NO complex, while the
      frequencies of the Fe-CO and C-O stretching modes are at 563 and 1972 cm(-1),
      respectively, for the CO complex. Also, the widths (fwhm) of the Fe-CO and C-O
      stretching modes are smaller than those observed in the corresponding complexes
      of other heme proteins. The unusual spectroscopic characteristics of the d(1)
      cofactor are discussed in terms of both its unique electronic properties and the
      strongly polar distal environment around the iron-bound ligand. It is likely that
      the influence of a highly ruffled structure of heme d(1) on its electronic
      properties is the major factor causing anomalous Fe-ligand vibrational
      frequencies.

PMID- 11535054
TI  - Mapping the functional topology of the animal fatty acid synthase by mutant
      complementation in vitro.
AB  - An in vitro mutant complementation approach has been used to map the functional
      topology of the animal fatty acid synthase. A series of knockout mutants was
      engineered, each mutant compromised in one of the seven functional domains, and
      heterodimers generated by hybridizing all possible combinations of the mutated
      subunits were isolated and characterized. Heterodimers comprised of a subunit
      containing either a beta-ketoacyl synthase or malonyl/acetyltransferase mutant,
      paired with a subunit containing mutations in any one of the other five domains,
      are active in fatty acid synthesis. Heterodimers in which both subunits carry a
      knockout mutation in either the dehydrase, enoyl reductase, keto reductase, or
      acyl carrier protein are inactive. Heterodimers comprised of a subunit containing
      a thioesterase mutation paired with a subunit containing a mutation in either the
      dehydrase, enoyl reductase, beta-ketoacyl reductase, or acyl carrier protein
      domains exhibit very low fatty acid synthetic ability. The results are consistent
      with a model for the fatty acid synthase in which the substrate loading and
      condensation reactions are catalyzed by cooperation of an acyl carrier protein
      domain of one subunit with the malonyl/acetyltransferase or beta-ketoacyl
      synthase domains, respectively, of either subunit. The beta-carbon-processing
      reactions, responsible for the complete reduction of the beta-ketoacyl moiety
      following each condensation step, are catalyzed by cooperation of an acyl carrier
      protein domain with the beta-ketoacyl reductase, dehydrase, and enoyl reductase
      domains associated exclusively with the same subunit. The chain-terminating
      reaction is carried out most efficiently by cooperation of an acyl carrier
      protein domain with the thioesterase domain of the same subunit. These results
      are discussed in the context of a revised model for the fatty acid synthase.

PMID- 11535055
TI  - Structural analysis of adenine phosphoribosyltransferase from Saccharomyces
      cerevisiae.
AB  - Adenine phosphoribosyltransferase (APRTase) is a widely distributed enzyme, and
      its deficiency in humans causes the accumulation of 2,8-dihydroxyadenine. It is
      the sole catalyst for adenine recycling in most eukaryotes. The most commonly
      expressed APRTase has subunits of approximately 187 amino acids, but the only
      crystal structure is from Leishmania donovani, which expresses a long form of the
      enzyme with 237 residues. Saccharomyces cerevisiae APRTase was selected as a
      representative of the short APRTases, and the structure of the apo-enzyme and
      sulfate bound forms were solved to 1.5 and 1.75 A, respectively. Yeast APRTase is
      a dimeric molecule, and each subunit is composed of a central five-stranded beta
      sheet surrounded by five alpha-helices, a structural theme found in all known
      purine phosphoribosyltransferases. The structures reveal several important
      features of APRTase function: (i) sulfate ions bound at the 5'-phosphate and
      pyrophosphate binding sites; (ii) a nonproline cis peptide bond (Glu67-Ser68) at
      the pyrophosphate binding site in both apo-enzyme and sulfate-bound forms; and
      (iii) a catalytic loop that is open and ordered in the apo-enzyme but open and
      disordered in the sulfate-bound form. Alignment of conserved amino acids in short
      APRTases from 33 species reveals 13 invariant and 15 highly conserved residues
      present in hinges, catalytic site loops, and the catalytic pocket. Mutagenesis of
      conserved residues in the catalytic loop, subunit interface, and
      phosphoribosylpyrophosphate binding site indicates critical roles for the tip of
      the catalytic loop (Glu106) and a catalytic site residue Arg69, respectively.
      Mutation of one loop residue (Tyr103Phe) increases k(cat) by 4-fold, implicating
      altered dynamics for the catalytic site loop.

PMID- 11535056
TI  - Structural basis for the catalysis and substrate specificity of homoserine
      kinase.
AB  - Homoserine kinase (HSK), the fourth enzyme in the aspartate pathway of amino acid
      biosynthesis, catalyzes the phosphorylation of L-homoserine (Hse) to L-homoserine
      phosphate, an intermediate in the production of L-threonine, L-isoleucine, and in
      higher plants, L-methionine. The high-resolution structures of Methanococcus
      jannaschii HSK ternary complexes with its amino acid substrate and ATP analogues
      have been determined by X-ray crystallography. These structures reveal the
      structural determinants of the tight and highly specific binding of Hse, which is
      coupled with local conformational changes that enforce the sequestration of the
      substrate. The delta-hydroxyl group of bound Hse is only 3.4 A away from the
      gamma-phosphate of the bound nucleotide, poised for the in-line attack at the
      gamma-phosphorus. The bound nucleotides are flexible at the triphosphate tail.
      Nevertheless, a Mg(2+) was located in one of the complexes that binds between the
      beta- and gamma-phosphates of the nucleotide with good ligand geometry and is
      coordinated by the side chain of Glu130. No strong nucleophile (base) can be
      located near the phosphoryl acceptor hydroxyl group. Therefore, we propose that
      the catalytic mechanism of HSK does not involve a catalytic base for activating
      the phosphoryl acceptor hydroxyl but instead is mediated via a transition state
      stabilization mechanism.

PMID- 11535057
TI  - Anesthetic stabilization of protein intermediates: myoglobin and halothane.
AB  - Halothane, an inhaled anesthetic, destabilizes the folded structure of myoglobin.
      To determine whether this is due to preferential interactions with less stable
      folded conformers of myoglobin versus the completely unfolded state, we used
      photoaffinity labeling, hydrogen exchange, fluorescence spectroscopy, and
      circular dichroism spectroscopy. Apomyoglobin was used as a model of a less
      stable conformer of myoglobin. Halothane destabilizes myoglobin and binds with
      low affinity and stoichiometry but stabilizes and binds with higher affinity to
      apomyoglobin. The same halothane concentration has no effect on cytochrome c
      stability. The apomyoglobin/halothane complex is favored at pH 6.5 as compared to
      pH 4.5 or pH 2.5. Halothane photoincorporates into several sites in apomyoglobin,
      some allosteric to the heme pocket. Guanidinium unfolding of myoglobin, monitored
      by CD spectroscopy, shows destabilization at less than 1.3 M Gdm but
      stabilization at greater than 1.3 M Gdm, consistent with the hypothesis that less
      stable conformers of myoglobin bind halothane preferentially. We suggest the
      structural feature underlying preferential binding to less stable conformers is
      an enlarged cavity volume distribution, since myoglobin has several intermediate
      sized cavities, while cytochrome c is more well packed and has no cavities
      detected by GRASP. Specific binding to less stable intermediates may underlie
      anesthetic potentiation of protein activity.

PMID- 11535058
TI  - Effects of sequential deletions of residues from the N- or C-terminus on the
      functions of epsilon subunit of the chloroplast ATP synthase.
AB  - Ten truncated mutants of chloroplast ATP synthase epsilon subunit from spinach
      (Spinacia oleracea), which had sequentially lost 1-5 amino acid residues from the
      N-terminus and 6-10 residues from the C-terminus, were generated by PCR. These
      mutants were overexpressed in Escherichia coli, reconstituted with soluble and
      membrane-bound CF(1), and the ATPase activity and proton conductance of thylakoid
      membrane were examined. Deletions of as few as 3 amino acid residues from the N
      terminus or 6 residues from the C-terminus of epsilon subunit significantly
      affected their ATPase-inhibitory activity in solution. Deletion of 5 residues
      from the N-terminus abolished its abilities to inhibit ATPase activity and to
      restore proton impermeability. Considering the consequence of interaction of
      epsilon and gamma subunit in the enzyme functions, the special interactions
      between the epsilon variants and the gamma subunit were detected in the yeast two
      hybrid system and in vitro binding assay. In addition, the structures of these
      mutants were modeled through the SWISS-MODEL Protein Modeling Server. These
      results suggested that in chloroplast ATP synthase, both the N-terminus and C
      terminus of the epsilon subunit show importance in regulation of the ATPase
      activity. Furthermore, the N-terminus of the epsilon subunit is more important
      for its interaction with gamma and some CF(o) subunits, and crucial for the
      blocking of proton leakage. Compared with the epsilon subunit from E. coli
      [Jounouchi, M., Takeyama, M., Noumi, T., Moriyama, Y., Maeda, M., and Futai, M.
      (1992) Arch. Biochem. Biophys. 292, 87-94; Kuki, M., Noumi, T., Maeda, M.,
      Amemura, A., and Futai, M. (1988) J. Biol. Chem. 263, 4335-4340], the chloroplast
      epsilon subunit is more sensitive to N-terminal or C-terminal truncations.

PMID- 11535059
TI  - Is hydrogen peroxide produced during iron(II) oxidation in mammalian
      apoferritins?
AB  - The ferritins are a class of iron storage and detoxification proteins that play a
      central role in the biological management of iron. These proteins have a
      catalytic site, "the ferroxidase site", located on the H-type subunit that
      facilitates the oxidation of Fe(II) to Fe(III) by O(2). Measurements during the
      past 10 years on a number of vertebrate ferritins have provided evidence that
      H(2)O(2) is produced at this diiron ferroxidase site. Recently reported
      experiments using three different analytical methods with horse spleen ferritin
      (HoSF) have failed to detect H(2)O(2) production in this protein [Lindsay, S.,
      Brosnahan, D., and Watt, G. D. (2001) Biochemistry 40, 3340-3347]. These findings
      contrast with earlier results reporting H(2)O(2) production in HoSF [Xu, B., and
      Chasteen, N. D. (1991) J. Biol. Chem. 266, 19965-19970]. Here a sensitive
      fluorescence assay and an assay based on O(2) evolution in the presence of
      catalase were used to demonstrate that H(2)O(2) is produced in HoSF as previously
      reported. However, because of the relatively few H-chain ferroxidase sites in
      HoSF and the reaction of H(2)O(2) with the protein, H(2)O(2) is more difficult to
      detect in this ferritin than in recombinant human H-chain ferritin (HuHF). The
      proper sequence of addition of reagents is important for measurement of the total
      amount of H(2)O(2) produced during the ferroxidation reaction.

PMID- 11535060
TI  - Fluorescence correlation spectroscopy detects galanin receptor diversity on
      insulinoma cells.
AB  - Fluorescence correlation spectroscopy (FCS) allows the study of interactions of
      fluorescently labeled ligand with receptors in living cells at single-molecule
      detection sensitivity. From the autocorrelation functions of fluorescence
      intensity fluctuations, the diffusion time of molecules through the confocal
      volume is analyzed, and from that, the molecular weights of free and bound
      molecules can be calculated. We have applied FCS to study the receptor diversity
      for the neuropeptide galanin (GAL) in cultured cells. FCS measurement of the
      fluorophore rhodamine-labeled GAL (Rh-GAL) has been performed in 0.2-fL confocal
      volume elements of the laser beam. The analysis of autocorrelation functions of
      Rh-GAL in solution above cells and at cell membranes demonstrates that the
      diffusion time of unbound Rh-GAL is 0.16 ms, whereas diffusion times of membrane
      bound Rh-GAL are 22 and 700 ms. Because both of the diffusion times (22 and 700
      ms) are much longer as compared to that of unbound Rh-GAL, they correspond to
      slow-diffusing complexes when Rh-GAL is bound to the cell membranes. Addition of
      excess nonlabeled GAL is accompanied by competitive displacement. Full saturation
      of the GAL binding is obtained at nanomolar concentrations. Scatchard analysis of
      binding data reveal one binding process, assuming one binding site per Rh-GAL (n
      = 1). On the other hand, the appearance of two diffusion times, 22 and 700 ms,
      suggests the existence of two subpopulations of GAL receptor complexes or two
      subtypes of GAL receptor not detected before. This makes an important point that
      FCS permits the identification of receptors, which were not possible to detect
      before by conventional binding techniques. The inhibitory effect of pertussis
      toxin on the GAL binding considers a G-protein-involved allosteric system,
      important for the clarification of essential steps in the G-protein-related
      signal transduction. This study is of pharmaceutical significance, since it will
      provide insights into how FCS can be used as a rapid technique for studying
      ligand-receptor interactions in living cells, which is one step forward for large
      scale drug screening in cell cultures.

PMID- 11535061
TI  - Arfophilin is a common target of both class II and class III ADP-ribosylation
      factors.
AB  - Arfophilin was first identified as a target protein for GTP-ARF5. The N-terminus
      of ARF5 (amino acids 2-17), which is distinct from that of class I or class III
      ARFs, is essential for binding to the C-terminus of arfophilin (amino acids 612
      756). This study using GST fusion proteins in pulldown experiments in CHO-K1 cell
      lysates showed that, unexpectedly, ARF6 also bound to full-length arfophilin or
      the C-terminus of arfophilin (amino acids 612-756) in a GTP-dependent manner.
      Studies with ARF1/ARF6 chimeras further showed that the amino acid sequence of
      residues 37-80 of ARF6, which is different from the corresponding sequences in
      class I and class II ARFs, was essential for binding to arfophilin. Both GTP-ARF5
      and GTP-ARF6 bound to arfophilin in CHO-K1 cell lysates, while GTP-ARF1 did not
      bind. In contrast, all three forms of ARF bound to arfaptin 2, with ARF1 showing
      the strongest binding. Yeast two-hybrid studies with wild-type, dominant
      negative, and constitutively active forms of ARF1, -5, and -6 and with ARF1/ARF6
      chimeras confirmed these results, except that constitutively active ARF6 was
      autoactivating. Our findings suggest that both class II and III ARFs may
      influence the same cellular pathways through arfophilin as a common downstream
      effector.

PMID- 11535063
TI  - Biosynthesis of the phosphodiester bond in coenzyme F(420) in the methanoarchaea.
AB  - The biochemical route for the formation of the phosphodiester bond in coenzyme
      F(420), one of the methanogenic coenzymes, has been established in the
      methanoarchaea Methanosarcina thermophila and Methanococcus jannaschii. The first
      step in the formation of this portion of the F(420) structure is the GTP
      dependent phosphorylation of L-lactate to 2-phospho-L-lactate and GDP. The 2
      phospho-L-lactate represents a new natural product that was chemically identified
      in Methanobacterium thermoautotrophicum, M. thermophila, and Mc. jannaschii.
      Incubation of cell extracts of both M. thermophila and Mc. jannaschii with
      [hydroxy-(18)O, carboxyl-(18)O(2)]lactate and GTP produced 2-phospho-L-lactate
      with the same (18)O distribution as found in both the starting lactate and the
      lactate recovered from the incubation. These results indicate that the carboxyl
      oxygens are not involved in the phosphorylation reaction. Incubation of Sephadex
      G-25 purified cell extracts of M. thermophila or Mc. jannaschii with 7,8
      didemethyl-8-hydroxy-5-deazariboflavin (Fo), 2-phospho-L-lactate, and GTP or ATP
      lead to the formation of F(420)-0 (F(420) with no glutamic acids). This
      transformation was shown to involve two steps: (i) the GTP- or ATP-dependent
      activation of 2-phospho-L-lactate to either lactyl(2)diphospho-(5')guanosine
      (LPPG) or lactyl(2)diphospho-(5')adenosine (LPPA) and (ii) the reaction of the
      resulting LPPG or LPPA with Fo to form F(420)-0 with release of GMP or AMP.
      Attempts to identify LPPG or LPPA intermediates by incubation of cell extracts
      with L-[U-(14)C]lactate, [U-(14)C]2-phospho-L-lactate, or [8-(3)H]GTP were not
      successful owing to the instability of these compounds toward hydrolysis.
      Synthetically prepared LPPG and LPPA had half-lives of 10 min at 50 degrees C (at
      pH 7.0) and decomposed into GMP or AMP and 2-phospho-L-lactate via cyclic 2
      phospho-L-lactate. No evidence for the functioning of the cyclic 2-phospho-L
      lactate in the in vitro biosynthesis could be demonstrated. Incubation of cell
      extracts of M. thermophila or Mc. jannaschii with either LPPG or LPPA and Fo
      generated F(420)-0. In summary, this study demonstrates that the formation of the
      phosphodiester bond in coenzyme F(420) follows a reaction scheme like that found
      in one of the steps of the DNA ligase reaction and in the biosynthesis of
      coenzyme B(12) and phospholipids.

PMID- 11535062
TI  - Adenylyl cyclase type II domains involved in Gbetagamma stimulation.
AB  - Mammalian particulate adenylyl cyclases contain two transmembrane regions (M(1)
      and M(2)) and two cytosolic domains (C(1) and C(2)) forming the catalytic core.
      The cytosolic domains are subdivided into a highly conserved region (part a) and
      a region with lower similarity (part b). Hypothetical models exist that account
      for the mechanism by which Galpha(s) and forskolin stimulate mammalian adenylyl
      cyclase. In contrast, little is known about how Gbetagamma dimers regulate
      catalysis. The so-called QEHA region located in the C(2a) domain of type II
      adenylyl cyclase has been proposed to represent a site of interaction. Here we
      show (i) that the QEHA region directly interacts with Gbetagamma but (ii) that it
      is of minor importance for the stimulation of type II adenylyl cyclase because it
      can be replaced by corresponding, nonidentical regions of other adenylyl cyclase
      isoforms without altering the stimulatory effect of Gbetagamma and (iii) that the
      C(1b) region is necessary for Gbetagamma to exert a stimulatory effect on
      adenylyl cyclase type II as in a C(1b) deletion mutant the Gbetagamma regulation
      was specifically impeded whereas the Galpha(s)- and forskolin-mediated
      stimulation was maintained.

PMID- 11535064
TI  - The reaction of yeast cystathionine beta-synthase is rate-limited by the
      conversion of aminoacrylate to cystathionine.
AB  - Our studies of the reaction mechanism of cystathionine beta-synthase from
      Saccharomyces cerevisiae (yeast) are facilitated by the spectroscopic properties
      of the pyridoxal phosphate coenzyme that forms a series of intermediates in the
      reaction of L-serine and L-homocysteine to form L-cystathionine. To characterize
      these reaction intermediates, we have carried out rapid-scanning stopped-flow and
      single-wavelength stopped-flow kinetic measurements under pre-steady-state
      conditions, as well as circular dichroism and fluorescence spectroscopy under
      steady-state conditions. We find that the gem-diamine and external aldimine of
      aminoacrylate are the primary intermediates in the forward half-reaction with L
      serine and that the external aldimine of aminoacrylate or its complex with L
      homocysteine is the primary intermediate in the reverse half-reaction with L
      cystathionine. The second forward half-reaction of aminoacrylate with L
      homocysteine is rapid. No primary kinetic isotope effect was obtained in the
      forward half-reaction with L-serine. The results provide evidence (1) that the
      formation of the external aldimine of L-serine is faster than the formation of
      the aminoacrylate intermediate, (2) that aminoacrylate is formed by the concerted
      removal of the alpha-proton and the hydroxyl group of L-serine, and (3) that the
      rate of the overall reaction is rate-limited by the conversion of aminoacrylate
      to L-cystathionine. We compare our results with cystathionine beta-synthase with
      those of related investigations of tryptophan synthase and O-acetylserine
      sulfhydrylase.

PMID- 11535065
TI  - The S(3) state of the oxygen-evolving complex in photosystem II is converted to
      the S(2)Y(Z)* state at alkaline pH.
AB  - Here we report an EPR signal that is induced by a pH jump to alkaline pH in the
      S(3) state of the oxygen-evolving complex in photosystem II. The S(3) state is
      first formed with two flashes at pH 6. Thereafter, the pH is changed in the dark
      prior to freezing of the sample. The EPR signal is 90-100 G wide and centered
      around g = 2. The signal is reversibly induced with a pK = 8.5 +/- 0.3 and is
      very stable with a decay half-time of 5-6 min. If the pH is changed in the dark
      from pH 8.6 to 6.0, the signal disappears although the S(3) state remains. We
      propose that the signal arises from the interaction between the Mn cluster and
      Y(Z), resulting in the spin-coupled S(2)Y(Z)(*) signal. Our data suggest that the
      potential of the Y(Z)(*)/Y(Z) redox couple is sensitive to the ambient pH in the
      S(3) state. The alkaline pH decreases the potential of the Y(Z)(*)/Y(Z) couple so
      that Y(Z) can give back an electron to the S(3) state, thereby obtaining the
      S(2)Y(Z)(*) EPR signal. The tyrosine oxidation also involves proton release from
      Y(Z), and the results support a mechanism where this proton is released to the
      bulk medium presumably via a close-lying base. Thus, the equilibrium is changed
      from S(3)Y(Z) to S(2)Y(Z)(*) by the alkaline pH. At normal pH (pH 5.5-7), this
      equilibrium is set strongly to the S(3)Y(Z) state. The results are discussed in
      relation to the present models of water oxidation. Consequences for the relative
      redox potentials of Y(Z)(*)/Y(Z) and S(3)/S(2) at different pH values are
      discussed. We also compare the pH-induced S(2)Y(Z)(*) signal with the S(2)Y(Z)(*)
      signal from Ca(2+)-depleted photosystem II.

PMID- 11535066
TI  - Adenovirus-mediated expression of caveolin-1 in mouse liver increases plasma high
      density lipoprotein levels.
AB  - Caveolae are 50-100 nm plasma membrane invaginations, which function in cell
      signaling and transcytosis, as well as in regulating cellular cholesterol
      homeostasis. These subcompartments of the plasma membrane are characterized by
      the presence of caveolin proteins. Recent studies have indicated that caveolae
      may be involved in the regulation of cellular cholesterol efflux to HDL, as well
      as selective uptake mediated by SR-BI. In the present study, we have determined
      the effect of caveolin-1 overexpression in mouse liver on plasma lipoprotein
      metabolism. We evaluated this effect using an adenovirus-mediated gene delivery
      system. C57BL/6J mice were injected with adenoviruses encoding either caveolin-1
      (Adcav-1) or green fluorescent protein (AdGFP) together with a transactivator
      adenovirus (AdtTA). We found that, after adenovirus injection, caveolin-1 was
      overexpressed in hepatocytes. Moreover, the recombinant protein was localized to
      the plasma membrane. We also found that caveolin-1 overexpression induced a
      marked change in the lipoprotein profile of injected animals. In caveolin-1
      overexpressing animals, plasma HDL-cholesterol levels were found to be
      approximately 2-fold elevated, as compared with control animals. To determine the
      effect of caveolin-1 on SR-BI-mediated selective uptake, we infected murine
      hepatocytes in culture with an adenoviral vector carrying the caveolin-1 cDNA or
      GFP as a control protein. We show that, in primary cultures of hepatocytes,
      caveolin-1 inhibits DiI-HDL uptake mediated by SR-BI. This result would
      mechanistically explain the increased plasma HDL-cholesterol levels we observed
      in caveolin-1 adenovirus-injected animals. In addition, caveolin-1 expression
      increased the secretion of apolipoprotein A-I in cultured hepatocytes and
      increased apolipoprotein A-I plasma levels in mice. Our study therefore
      demonstrates an important role for caveolin-1 in regulating HDL metabolism.

PMID- 11535067
TI  - The ubiquitous aldehyde reductase (AKR1A1) oxidizes proximate carcinogen trans
      dihydrodiols to o-quinones: potential role in polycyclic aromatic hydrocarbon
      activation.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are metabolized to trans-dihydrodiol
      proximate carcinogens by human epoxide hydrolase (EH) and CYP1A1. Human
      dihydrodiol dehydrogenase isoforms (AKR1C1-AKR1C4), members of the aldo-keto
      reductase (AKR) superfamily, activate trans-dihydrodiols by converting them to
      reactive and redox-active o-quinones. We now show that the constitutively and
      widely expressed human AKR, aldehyde reductase (AKR1A1), will oxidize potent
      proximate carcinogen trans-dihydrodiols to their corresponding o-quinones. cDNA
      encoding AKR1A1 was isolated from HepG2 cells, overexpressed in Escherichia coli,
      purified to homogeneity, and characterized. AKR1A1 oxidized the potent proximate
      carcinogen (+/-)-trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene with a higher
      utilization ratio (V(max)/K(m)) than any other human AKR. AKR1A1 also displayed a
      high V(max)/K(m) for the oxidation of 5-methylchrysene-7,8-diol,
      benz[a]anthracene-3,4-diol, 7-methylbenz[a]anthracene-3,4-diol, and 7,12
      dimethylbenz[a]anthracene-3,4-diol. AKR1A1 displayed rigid regioselectivity by
      preferentially oxidizing non-K-region trans-dihydrodiols. The enzyme was
      stereoselective and oxidized 50% of each racemic PAH trans-dihydrodiol tested.
      The absolute stereochemistries of the reactions were assigned by circular
      dichroism spectrometry. AKR1A1 preferentially oxidized the metabolically relevant
      (-)-benzo[a]pyrene-7(R),8(R)-dihydrodiol. AKR1A1 also preferred (-)
      benz[a]anthracene-3(R),4(R)-dihydrodiol, (+)-7-methylbenz[a]anthracene-3(S),4(S)
      dihydrodiol, and (-)-7,12-dimethylbenz[a]anthracene-3(R),4(R)-dihydrodiol. The
      product of the AKR1A1-catalyzed oxidation of (+/-)-trans-7,8-dihydroxy-7,8
      dihydrobenzo[a]pyrene was trapped with 2-mercaptoethanol and characterized as a
      thioether conjugate of benzo[a]pyrene-7,8-dione by LC/MS. Multiple human tissue
      expression array analysis showed coexpression of AKR1A1, CYP1A1, and EH,
      indicating that trans-dihydrodiol substrates are formed in the same tissues in
      which AKR1A1 is expressed. The ability of this general metabolic enzyme to divert
      trans-dihydrodiols to o-quinones suggests that this pathway of PAH activation may
      be widespread in human tissues.

PMID- 11535068
TI  - Influence of intervening mismatches on long-range guanine oxidation in DNA
      duplexes.
AB  - A systematic investigation of the efficiency of oxidative damage at guanine
      residues through long-range charge transport was carried out as a function of
      intervening base mismatches. A series of DNA oligonucleotides were synthesized
      that incorporate a ruthenium intercalator linked covalently to the 5' terminus of
      one strand and containing two 5'-GG-3' sites in the complementary strand. Single
      base mismatches were introduced between the two guanine doublet steps, and the
      efficiency of transport through the mismatches was determined through
      measurements of the ratio of oxidative damage at the guanine doublets distal
      versus proximal to the intercalated ruthenium oxidant. Differing relative extents
      of guanine oxidation were observed for the different mismatches. The damage ratio
      of oxidation at the distal versus proximal site for the duplexes containing
      different mismatches varies in the order GC approximately GG approximately GT
      approximately GA > AA > CC approximately TT approximately CA approximately CT.
      For all assemblies, damage found with the Delta-Ru diastereomer was found to be
      greater than with the Lambda-diastereomer. The extent of distal/proximal guanine
      oxidation in different mismatch-containing duplexes was compared with the helical
      stability of the duplexes, electrochemical data for intercalator reduction on
      different mismatch-containing DNA films, and base-pair lifetimes for oligomers
      containing the different mismatches derived from 1H NMR measurements of the imino
      proton exchange rates. While a clear correlation is evident both with helix
      stability and electrochemical data monitoring reduction of an intercalator
      through DNA films, damage ratios correlate most closely with base-pair lifetimes.
      Competitive hole trapping at the mismatch site does not appear to be a key factor
      governing the efficiency of transport through the mismatch. These results
      underscore the importance of base dynamics in modulating long-range charge
      transport through the DNA base-pair stack.

PMID- 11535069
TI  - Sequence-specific trapping of topoisomerase I by DNA binding polyamide
      camptothecin conjugates.
AB  - Hairpin pyrrole-imidazole polyamides are synthetic ligands that bind in the minor
      groove of DNA with affinities and specificities comparable to those of DNA
      binding proteins. Three polyamide-camptothecin conjugates 1-3 with linkers
      varying in length between 7, 13, and 18 atoms were synthesized to trap the enzyme
      Topoisomerase I and induce cleavage at predetermined DNA sites. One of these,
      polyamide-camptothecin conjugate 3 at nanomolar concentration (50 nM) in the
      presence of Topo I (37 degrees C), induces DNA cleavage between three and four
      base pairs from the polyamide binding site in high yield (77%).

PMID- 11535070
TI  - Photochemical generation of nitric oxide from 6-nitrobenzo[a]pyrene.
AB  - Photolabile 6-nitrobenzo[a]pyrene (6-nitroBaP) released nitric oxide (NO) under
      visible-light irradiation. The generation of NO and the concomitant formation of
      the 6-oxyBaP radical were confirmed by ESR. BaP quinones were also detected as
      further oxidized products of the 6-oxyBaP radical. No such photodegradation was
      observed with other nitrated BaPs, such as 1-nitroBaP and 3-nitroBaP. DNA-strand
      breakage, caused by photoexcited 6-nitroBaP, was closely related to its NO
      releasing activity. MO calculations of nitrated BaP suggest that the
      perpendicular conformation of the nitro substituent to the aromatic ring is
      important for the release of NO with light. These findings may be useful for the
      development of a new type of NO donor.

PMID- 11535071
TI  - Interstrand side chain--side chain interactions in a designed beta-hairpin:
      significance of both lateral and diagonal pairings.
AB  - The contributions of interstrand side chain-side chain contacts to beta-sheet
      stability have been examined with an autonomously folding beta-hairpin model
      system. RYVEV(D)PGOKILQ-NH2 ((D)P = D-proline, O = ornithine) has previously been
      shown to adopt a beta-hairpin conformation in aqueous solution, with a two
      residue loop at D-Pro-Gly. In the present study, side chains that display
      interstrand NOEs (Tyr-2, Lys-9, and Leu-11) are mutated to alanine or serine, and
      the conformational impact of the mutations is assessed. In the beta-hairpin
      conformation Tyr-2 and Leu-11 are directly across from one another (non-hydrogen
      bonded pair). This "lateral" juxtaposition of two hydrophobic side chains appears
      to contribute to beta-hairpin conformational stability, which is consistent with
      results from other beta-sheet model studies and with statistical analyses of
      interstrand residue contacts in protein crystal structures. Interaction between
      the side chains of Tyr-2 and Lys-9 also stabilizes the beta-hairpin conformation.
      Tyr-2/Lys-9 is a "diagonal" interstrand juxtaposition because these residues are
      not directly across from one another in terms of the hydrogen bonding registry
      between the strands. This diagonal interaction arises from the right-handed twist
      that is commonly observed among beta-sheets. Evidence of diagonal side chain-side
      chain contacts has been observed in other autonomously folding beta-sheet model
      systems, but we are not aware of other efforts to determine whether a diagonal
      interaction contributes to beta-sheet stability.

PMID- 11535072
TI  - Enzyme catalysis of 1,2-amino shifts: the cooperative action of B6, B12, and
      aminomutases.
AB  - Ab initio molecular orbital theory is used to investigate 1,2-amino shifts
      catalyzed by aminomutases, coenzyme B12, and vitamin B6 (in the form of pyridoxal
      5'-phosphate or PLP). Our calculations suggest essential catalytic roles for each
      of B12, B6, and the enzyme in aminomutase-catalyzed reactions. In the first
      place, coenzyme B12 provides a source of abstracting radicals, allowing the
      rearrangement reaction to take place on the radical surface. The involvement of
      radicals is supported by comparison of experimental and theoretical electron
      paramagnetic resonance parameters. Next, B6 allows the enzyme to lower the
      barrier height by introducing a double bond (allowing a low-energy intramolecular
      rearrangement pathway) and by providing a suitable site for partial protonation
      (preventing overstabilization of the reaction intermediate which could lead to
      enzyme inactivation). The PLP hydroxyl group is also identified as an important
      participant in these reactions. Finally, the enzyme holds the various reaction
      components in place and is the source of acidic functional groups that can
      provide partial protonation.

PMID- 11535073
TI  - Chemical and structural characterization of the interaction of bleomycin A2 with
      d(CGCGAATTCGCG)2. efficient, double-strand DNA cleavage accessible without
      structural reorganization.
AB  - A detailed description of the interaction between Fe(II).bleomycin A2 and the
      Dickerson-Drew dodecamer d(CGCGAATTCGCG)2 is presented. The reaction between
      bleomycin and this substrate leads to DNA cleavage at two major sites, adenosine5
      and cytidine11, and two minor sites, cytidine3 and thymidine8. The pattern and
      relative intensities of cleavage at these sites was not entirely consistent with
      what would be predicted based on the preference of the drug for cleavage at the
      pyrimidines of 5'-GC-3' and 5'-GT-3' sites. Insight into the origins of the
      apparent alteration of selectivity was provided by examination of the structure
      of the duplex which had been determined by X-ray crystallography. This indicated
      that the C4' hydrogens of the two nucleotides located at the strongest cleavage
      sites, C11 on one strand and A5 on the other, were oriented toward each other in
      the minor groove. Two-dimensional NMR measurements and molecular dynamics
      modeling indicated that a metalloBLM could bind to the duplex in an orientation
      that positioned the metal center roughly equally close to each of these hydrogen
      atoms. On the basis of this observation, it was proposed that these two residues
      represented a double-stranded BLM cleavage site. This hypothesis was tested
      through the study of the BLM-mediated cleavage of the related decamer duplex,
      d(CGCGAATTCG).d(CGAATTCGCG), as well as the hairpin sequence
      d(CGCGAATTCGIIIITTTTCCCCCGAATTCGCG). By the use of the hairpin oligonucleotide
      32P-labeled alternately at the 5' and 3'-ends, unequivocal evidence was obtained
      for BLM-mediated double-strand cleavage. Quantitative analysis of the proportion
      of damage involving double-strand cleavage was effected by the use of the hairpin
      substrate; for damage initiated at the predominant cleavage site (cytidine31,
      analogous to cytidine11 in the dodecanucleotide), it is estimated that 43% of all
      damage leads to double-stranded lesions. The exceptional efficiency of double
      strand cleavage observed in this system must reflect the spatial proximity and
      orientation of the two sugar H's whose abstraction is required to produce double
      stranded lesions.

PMID- 11535074
TI  - Understanding solid/solid organic reactions.
AB  - The concept of an organic reaction between two macroscopic solid particles is
      investigated. Thus, we study several reactions that have been recently reported
      to proceed "in the solid phase" and clearly show that, in most cases, grinding
      the two solid reactants together results in the formation of a liquid phase. This
      is true both for catalytic transformations (e.g., aldol condensations and
      oligomerization of benzylic compounds) and for noncatalytic reactions (Baeyer
      Villiger oxidations, oxidative coupling of naphthols using iron chloride,
      condensation of amines and aldehydes to form azomethines, homo-etherification of
      benzylic alcohols using p-toluenesulfonic acid, and nuclear aromatic bromination
      with NBS). This liquefaction implies the existence of a eutectic mixture with
      T(fusion) below ambient temperature (although both reagents have higher than
      ambient melting points). In cases where heating is required, it is again clear
      that a phase change (from solid to liquid) occurs, explaining the observed
      reaction kinetics. On the basis of 19 experimental examples, we discuss the
      possibility of solid-phase organic reactions and the implications of these
      findings to the reaction between two solid reagents. A general description of
      such reactive systems is proposed, based on a consideration of the potential for
      eutectic (or peritectic) formation between the constituents of the liquid phases
      that arise during the process of mechanical mixing of the solid reagents and
      products.

PMID- 11535075
TI  - Catalytic amplification of the soft lithographic patterning of Si.
      Nonelectrochemical orthogonal fabrication of photoluminescent porous Si pixel
      arrays.
AB  - Photoluminescent, porous silicon pixel arrays were fabricated via a Pt-promoted
      wet etching of p-type Si(100) using a 1:1:1 EtOH/HF/H2O2 solution. The pixels
      were fabricated with micrometer-scale design rules on a silicon substrate that
      had been modified with an octadecyltrichlorosilane (OTS) monolayer patterned
      using microcontact printing. The printed OTS layer serves as an orthogonal resist
      template for the deposition of a Pt(0) complex, which preferentially deposits
      metal species in areas not covered with OTS. The Pt centers generate a localized
      oxidative dissolution process that pits the Si in the Pt-coated regions,
      resulting in the formation of a porous silicon microstructure that luminesces
      around 580 nm upon illumination with a UV source. Scanning electron microscopy
      and fluorescence microscopy images of the fabricated porous silicon structures
      showed that features in the size range of approximately 10-150 microm, and
      possibly smaller, can be generated by this catalytically amplified soft
      lithographic patterning method. Importantly, the OTS acts as an etch mask, so
      that, even with significant hole transport, etching is confined to areas coated
      with the Pt(0) complex.

PMID- 11535076
TI  - Template-assisted self-assembly: a practical route to complex aggregates of
      monodispersed colloids with well-defined sizes, shapes, and structures.
AB  - This paper describes a strategy that combines physical templating and capillary
      forces to assemble monodispersed spherical colloids into uniform aggregates with
      well-controlled sizes, shapes, and structures. When an aqueous dispersion of
      colloidal particles was allowed to dewet from a solid surface that had been
      patterned with appropriate relief structures, the particles were trapped by the
      recessed regions and assembled into aggregates whose structures were determined
      by the geometric confinement provided by the templates. We have demonstrated the
      capability and feasibility of this approach by assembling polystyrene beads and
      silica colloids (> or =150 nm in diameter) into complex aggregates that include
      polygonal or polyhedral clusters, linear or zigzag chains, and circular rings. We
      have also been able to generate hybrid aggregates in the shape of HF or H2O
      molecules that are composed of polymer beads having different diameters, polymer
      beads labeled with different organic dyes, and a combination of polymeric and
      inorganic beads. These colloidal aggregates can serve as a useful model system to
      investigate the hydrodynamic and optical scattering properties of colloidal
      particles having nonspherical morphologies. They should also find use as the
      building blocks to generate hierarchically self-assembled systems that may
      exhibit interesting properties highly valuable to areas ranging from photonics to
      condensed matter physics.

PMID- 11535077
TI  - Ab initio molecular dynamics-based assignment of the protonation state of
      pepstatin A/HIV-1 protease cleavage site.
AB  - A recent 13C NMR experiment (Smith et al. Nature Struct. Biol. 1996, 3, 946-950)
      on the Asp 25-Asp25' dyad in pepstatin A/HIV-1 protease measured two separate
      resonance lines, which were interpreted as being a singly protonated dyad. We
      address this issue by performing ab initio molecular dynamics calculations on
      models for this site accompanied by calculations of 13C NMR chemical shifts and
      isotopic shifts. We find that already on the picosecond time-scale the model
      proposed by Smith et al. is not stable and evolves toward a different
      monoprotonated form whose NMR pattern differs from the experimental one. We
      suggest, instead, a different protonation state in which both aspartic groups are
      protonated. Despite the symmetric protonation state, the calculated 13C NMR
      properties are in good agreement with the experiment. We rationalize this result
      using a simple valence bond model, which explains the chemical inequality of the
      two C sites. The model calculations, together with our calculations on the
      complex, allow also the rationalization of 13C NMR properties on other HIV-1
      PR/inhibitor complexes. Both putative binding of the substrate to the free
      enzyme, which has the dyad singly protonated (Piana, S.; Carloni, P. Proteins:
      Struct., Funct., Genet. 2000, 39, 26-36), and pepstatin A binding to the
      diprotonated form are consistent with the inverse solvent isotope effect on the
      onset of inhibition of pepsin by pepstatin and the kinetic iso-mechanism proposed
      for aspartic proteases (Cho, T.-K.; Rebholz, K.; Northrop, D.B. Biochemistry
      1994, 33, 9637-9642).

PMID- 11535078
TI  - Single-site beta-diiminate zinc catalysts for the alternating copolymerization of
      CO2 and epoxides: catalyst synthesis and unprecedented polymerization activity.
AB  - Synthetic routes to zinc beta-diiminate complexes are reported. The synthesis of
      11 beta-diimine [(BDI)-H] ligands, with varying N-aryl substituents and bridging
      structures, is described. These ligands are converted to (BDI)ZnX complexes (X =
      OAc, Et, N(SiMe3)2, Br, Cl, OH, OMe, O(i)Pr). X-ray structural data revealed that
      all zinc complexes examined exist as micro-X-bridged dimers in the solid state,
      with the exception of the zinc ethyl and amido complexes which were monomeric.
      Complexes of the form (BDI)ZnOR (R = alkyl, acyl) and (BDI)ZnN(SiMe3)2 are highly
      active catalysts for the alternating copolymerization of epoxides and CO2.
      Copolymerizations of cyclohexene oxide (CHO) and CO2 with (BDI-1)ZnX [(BDI-1) = 2
      ((2,6-diisopropylphenyl)amido)-4-((2,6-diisopropylphenyl)imino)-2-pentene)] and
      (BDI-2)ZnX [(BDI-2) = 2-((2,6-diethylphenyl)amido)-4-((2,6-diethylphenyl)imino)-2
      pentene)], where X = OAc, Et, N(SiMe3)2, Br, Cl, OH, OMe, O(i)Pr, were attempted
      at 50 degrees C and 100 psi CO2. Complexes with X = OAc, N(SiMe3)2, OMe, O(i)Pr
      all produced polycarbonate by the alternated insertion of CHO and CO2 with
      similar catalytic activities, comparable molecular weights, and narrow molecular
      weight distributions (MWD approximately 1.1), indicating the copolymerizations
      are living. Furthermore, ligand effects were shown to dramatically influence the
      polymerization activity as minor steric changes accelerated or terminated the
      polymerization activity.

PMID- 11535079
TI  - Total synthesis of cyclic ADP-carbocyclic-ribose, a stable mimic of Ca2+
      mobilizing second messenger cyclic ADP-ribose.
AB  - The synthesis of cyclic ADP-carbocyclic-ribose (cADPcR, 4) designed as a stable
      mimic of cyclic ADP-ribose (cADPR, 1), a Ca2+-mobilizing second messenger, was
      achieved using as the key step a condensation reaction with the
      phenylthiophosphate-type substrate 14 to form an intramolecular pyrophosphate
      linkage. The N-1-carbocyclic-ribosyladenosine derivative 16 was prepared via the
      condensation between the imidazole nucleoside derivative 17, prepared from AICA
      riboside (19), and the readily available optically active carbocyclic amine 18.
      Compound 16 was then converted to the corresponding 5' '-phosphoryl-5'
      phenylthiophosphate derivatives 14. Treatment of 14 with AgNO3 in the presence of
      molecular sieves (3 A) in pyridine at room temperature gave the desired
      cyclization product 32 in 93% yield, and subsequent acidic treatment provided the
      target cADPcR (4). This represents a general method for synthesizing biologically
      important cyclic nucleotides of this type. 1H NMR analysis of cADPcR suggested
      that its conformation in aqueous medium is similar to that of cADPR. cADPcR,
      unlike cADPR, was stable under neutral and acidic conditions, where under basic
      conditions, it formed the Dimroth-rearranged N6-cyclized product 34. cADPcR was
      also stable in rat brain membrane homogenate which has cADPR degradation
      activity. Furthermore, cADPcR was resistant to the hydrolysis by CD38 cADPR
      hydrolase, while cADPR was rapidly hydrolyzed under the same conditions. When
      cADPcR was injected into sea urchin eggs, it caused a significant release of Ca2+
      in the cells, an effect considerably stronger than that of cADPR. Thus, cADPcR
      was identified as a stable mimic of cADPR.

PMID- 11535080
TI  - Thermal and photochemical solvolysis of (E)- and (Z)-2-phenyl-1
      propenyl(phenyl)iodonium tetrafluoroborate: benzenium and primary vinylic cation
      intermediates.
AB  - The thermal and photochemical solvolysis of the two stereoisomeric 2-phenyl-1
      propenyl(phenyl)iodonium tetrafluoroborates has been investigated in alcoholic
      solvents of varying nucleophilicity. The product profiles and rates of product
      formation in the thermal reaction are all compatible with a mechanism involving
      cleavage of the vinylic C-I bond assisted by the group in the trans position
      (methyl or phenyl), always leading to rearranged products. Depending on the
      nucleophilicity of the solvent, the primarily formed cations may or may not
      further rearrange to more stable isomers. The less reactive Z compound also
      yields some unrearranged vinyl ether product in the more nucleophilic solvents
      via an in-plane S(N)2 mechanism. The mechanism of the photolysis involves direct,
      unassisted cleavage of the vinylic, and aromatic, C-I bond in an S(N)1 mechanism.
      This produces a primary vinyl cation, which is partially trapped prior to
      rearrangement in methanol. The unrearranged vinyl ethers are mainly formed with
      retention of configuration via a lambda3-iodonium/solvent complex in an S(N)i
      mechanism. Thermal and photochemical solvolyses of iodonium salts are
      complementary techniques for the generation of different cation intermediates
      from the same substrate.

PMID- 11535081
TI  - Sulfide-mediated dehydrative glycosylation.
AB  - The development of a new method for glycosylation with 1-hydroxy glycosyl donors
      employing dialkyl sulfonium reagents is described. The process employs the
      reagent combination of a dialkyl sulfide and triflic anhydride to effect anomeric
      bond constructions. This controlled dehydrative coupling of various C(1)
      hemiacetal glycosyl donors and nucleophilic acceptors proceeds by way of a
      sulfide-to-sulfoxide oxidation process in which triflic anhydride serves as the
      oxidant.

PMID- 11535082
TI  - Unusually accelerated silylmethyl transfer from tin in stille coupling:
      implication of coordination-driven transmetalation.
AB  - The palladium-catalyzed cross-coupling reaction of 2-PyMe2SiCH2SnBu3 with aryl
      iodide (Ar-I) exclusively produced the 2-PyMe2SiCH2 transferred product 2
      PyMe2SiCH2Ar. The relative transfer ability of organic group from tin was found
      to be 2-PyMe2SiCH2 >> Ph > Me > Bu >> PhMe2SiCH2, which implies the beneficial
      pyridyl-to-palladium coordination effect. Thus, the transfer of the silylmethyl
      group from tin to palladium was remarkably accelerated by simply appending the 2
      pyridyl group on silicon. The pyridyl-to-palladium coordination was validated in
      the palladium(II) complex 2-PyMe2SiCH2PdClPPh3 by 1H NMR and X-ray crystal
      structure analysis. The cross-coupling product was used for further
      transformations. The C-Si oxidation of the cross-coupling product 2-PyMe2SiCH2Ar
      afforded ArCH2OH in high yield. The fluoride ion-catalyzed 1,2-addition of 2
      PyMe2SiCH2Ar to carbonyl compound (RR'C=O) gave ArCH2C(OH)RR' in high yield.

PMID- 11535083
TI  - Remarkable spectator ligand effect on the rate constant of ligand substitution of
      (aqua)ruthenium(II) complexes.
AB  - The influence of two different di(1-pyrazolyl)alkane ligands on the rate constant
      of aqua ligand substitution of ruthenium(II) complexes with the formula
      [Ru(H2O)(L2)(tpmm)]2+ (L2 = di(1-pyrazolyl)methane (DPMet) or 2,2-di(1
      pyrazolyl)propane (DPPro)) was investigated. A 9.4 x 10(5)-fold increase in the
      rate constant of ligand substitution at pH = 6.86 was observed when DPMet was
      replaced with DPPro. This remarkable increase was unexpected, considering that
      these bidentate ligands appear quite similar. To help lend insight into this
      dramatic spectator ligand effect, the activation parameters for the ligand
      substitution reactions were determined, and single-crystal X-ray data were
      collected on the structurally analogous (chloro)ruthenium(II) complexes,
      [Ru(Cl)(L2)(tpmm)]+. These results are discussed in the context of a
      heteroscorpionate effect exerted by the DPPro ligand.

PMID- 11535084
TI  - Helical ribbon aggregate composed of a crown-appended cholesterol derivative
      which acts as an amphiphilic gelator of organic solvents and as a template for
      chiral silica transcription.
AB  - New crown-appended cholesterol-based organogelator 1, which has two cholesterol
      skeletons as a chiral aggregate-forming site, two amino groups as an acidic
      proton-binding site, and one crown moiety as a cation-binding site, was
      synthesized, and the gelation ability was evaluated in organic solvents. It can
      gelate acetic acid, acetonitrile, acetone, ethanol, 1-butanol, 1-hexanol, DMSO,
      and DMF under 1.0 wt %, indicating that 1 acts as a versatile gelator of various
      organic solvents. To characterize the aggregation mode in the organogel system,
      we observed a CD spectrum of the acetic acid gel 1. In the CD spectrum, the
      lambda(theta)=0 value appears at 353 nm, which is the same as the absorption
      maximum lambda(max) = 353 nm. The positive sign for the first Cotton effect
      indicates that the dipole moments of azobenzene chromophores tend to orient in a
      clockwise direction. Very surprisingly, the TEM images of the 1 + acetic acid gel
      resulted in the helical ribbon and the tubular structures. Sol-gel polymerization
      of tetraethoxysilane was carried out using 1 in the gel phase. The silica
      obtained from the 1 + acetic acid gel showed the helical ribbon with 1700-1800-nm
      pitches and the tubular structure of the silica with approximately 560-nm outer
      diameter. As far as can be recognized, all the helicity possesses a right-handed
      helical motif. Since the exciton-coupling band of the organogel also shows R
      (right-handed) helicity, we consider that a microscopic helicity is reflected by
      a macroscopic helicity.

PMID- 11535085
TI  - Growth of Sr6Rh5O15 single crystals from high-temperature solutions: structure
      determination using the traditional 3-D and the 4-D superspace group methods and
      magnetic measurements on oriented single crystals.
AB  - Single crystals of Sr6Rh5O15 were grown from a molten potassium carbonate flux.
      The structure was solved by both the traditional 3-D crystallographic approach
      and the 4-D superspace group approach using JANA2000. Both methods produced an
      equivalent structure determination, thereby confirming the 4-D superspace group
      approach as an effective structure solution method for 3-D commensurate composite
      structures. Sr6Rh5O15 corresponds to the n = 1, m = 1 member of the
      A3n+3mA'nB3m+nO9m+6n family of 2H hexagonal perovskite-related oxides. This
      compound is characterized by pseudo-one-dimensional polyhedral chains of four
      face-sharing RhO6 octahedra followed by one RhO6 trigonal prism. These chains in
      turn are separated by [Sr](infinity) chains. Magnetic measurements were carried
      out on oriented single crystals, and a very large magnetic anisotropy in the
      magnetic susceptibility was observed.

PMID- 11535086
TI  - The location and ordering of fluoride ions in pure silica zeolites with framework
      types IFR and STF; implications for the mechanism of zeolite synthesis in
      fluoride media.
AB  - Single-crystal X-ray diffraction studies carried out at a synchrotron radiation
      source have allowed the structure solution and location of fluoride ions inside
      as-made pure silica zeolites with the IFR and STF framework structures. The local
      environment of the fluoride has been identified, and unusual ordering of the
      fluoride ions has been discovered in both cases. The details of the crystal
      structures are used to suggest structural features that are important in
      determining the ordering of fluoride ions in zeolites. A mechanism for how the
      fluoride ordering occurs is suggested for IFR and STF based on the local
      structure of small cages that make up these zeolites, and the implications for
      the mechanism of crystal growth are discussed.

PMID- 11535087
TI  - A new oxoanion: [IO]3- containing I(V) with a stereochemically active lone-pair
      in the silver uranyl iodate tetraoxoiodate(V), Ag4(UO2)4(IO3)2(IO4)2O2 .
AB  - The hydrothermal reaction of elemental Ag, or water-soluble silver sources, with
      UO3 and I2O5 at 200 degrees C for 5 days yields Ag4(UO2)4(IO3)2(IO4)2O2 in the
      form of orange fibrous needles. Single-crystal X-ray diffraction studies on this
      compound reveal a highly complex network structure consisting of three
      interconnected low-dimensional substructures. The first of these substructures
      are ribbons of UO8 hexagonal bipyramids that edge-share to form one-dimensional
      chains. These units further edge-share with pentagonal bipyramidal UO7 units to
      create ribbons. The edges of the ribbons are partially terminated by
      tetraoxoiodate(V), [IO4]3-, anions. The uranium oxide ribbons are joined by
      bridging iodate ligands to yield two-dimensional undulating sheets. These sheets
      help to form, and are linked together by, one-dimensional chains of edge-sharing
      AgO7 capped octahedral units and ribbons formed by corner-sharing capped trigonal
      planar AgO4 polyhedra, AgO6 capped square pyramids, and AgO6 octahedra. The
      [IO4]3- anions in Ag4(UO2)4(IO3)2)(IO4)2O2 are tetraoxoiodate(V), not
      metaperiodate, and contain I(V) with a stereochemically active lone-pair. Bond
      valence sum calculations are consistent with this formulation. Differential
      scanning calorimetry measurements show distinctly different thermal behavior of
      Ag4(UO2)4(IO3)2(IO4)2O2 versus other uranyl iodate compounds with endotherms at
      479 and 494 degrees C. Density functional theory (DFT) calculations demonstrate
      that the approximate C2v geometry of the [IO4]3- anion can be attributed to a
      second-order Jahn-Teller distortion. DFT optimized geometry for the [IO4]3- anion
      is in good agreement with those measured from single-crystal X-ray diffraction
      studies on Ag4(UO2)4(IO3)2(IO4)2O2.

PMID- 11535088
TI  - Conformational studies of methyl 3-O-methyl-alpha-D-arabinofuranoside: an
      approach for studying the conformation of furanose rings.
AB  - A computational method for probing furanose conformation has been developed using
      a methylated monosaccharide derivative 1. First, a large library of conformers
      was generated by a systematic pseudo Monte Carlo search followed by optimization
      with the AMBER molecular mechanics force field. A subset of these conformers was
      then subjected to ab initio and density functional theory calculations in both
      the gas and aqueous phases. These calculations indicate that entropic
      contributions to the Gibbs free energy are important determinants of the
      Boltzmann distribution for the conformational preferences of 1 in the gas phase.
      The results obtained at each level of theory are discussed and compared with the
      experimentally determined conformer distribution from NMR studies in aqueous
      solution. In addition, the ability of each level of theory to reproduce the
      experimentally measured 1H-1H coupling constants in 1 is discussed. Empirical
      Karplus equations and density functional theory methods were used to determine
      average 3J(H1,H2), 3J(H2,H3), and 3J(H3,H4) for each level of theory. On the
      basis of this comparison, consideration of solvation with the MN-GSM model
      provided good agreement with the experimental data.

PMID- 11535089
TI  - On the aromaticity of square planar Ga4(2-) and In4(2-) in gaseous NaGa4- and
      NaIn4- clusters.
AB  - We investigated the electronic structure and chemical bonding of two bimetallic
      clusters NaGa4- and NaIn4-. Photoelectron spectra of the anions were obtained and
      compared with ab initio calculations. We found that the ground state of the two
      anions contains a square planar dianion interacting with a Na+ cation. The Ga4(2
      ) and In4(2-) dianions both possess two delocalized pi electrons and are
      considered to be aromatic, similar to that recently found in Al4(2-). Using
      calculations for a model compound, we showed that a recently synthesized Ga4
      organometallic compound also contains an aromatic -Ga4(2-)- unit, analogous to
      the gaseous clusters.

PMID- 11535090
TI  - Theoretical evaluation of the origin of the regio- and stereoselectivity in the
      Diels-Alder reactions of dialkylvinylboranes: studies on the reactions of
      vinylborane, dimethylvinylborane, and vinyl-9-BBN with trans-piperylene and
      isoprene.
AB  - Ab initio and DFT calculations have been performed to study the origin of the
      regio- and stereoselectivity of the Diels-Alder reactions of dialkylvinylboranes
      with substituted dienes. B3LYP/6-31G energies of the transition structures for
      the reactions of dimethylvinylborane and vinyl-9-BBN with trans-piperylene and
      isoprene yielded calculated ratios which are in very good agreement with
      experimental values. Nonclassical carbon-boron [4+3] secondary orbital
      interactions seem to account for the high endo stereoselectivity of these
      reactions. However, C-B interactions become less important when the bulkiness of
      the alkyl groups attached to boron increases. Both endo and exo transition
      structures for the reactions of dimethylvinylborane and vinyl-9-BBN adopt
      classical [4+2] character. This study also extends Singleton's investigation on
      butadiene to regioselectivity. FMO theory has been used to rationalize the lack
      of regioselectivity in the reactions of dimethylvinylborane. The anomalous meta
      regioselectivity of the Diels-Alder reaction of vinyl-9-BBN with trans-piperylene
      is mainly caused by steric effects.

PMID- 11535091
TI  - Adsorption configuration and local ordering of silicotungstate anions on Ag(100)
      electrode surfaces.
AB  - X-ray reflectivity, cyclic voltammetry, and scanning tunneling microscopy (STM)
      are used to examine the structure of alpha-SiW12O4(4-) or silicotungstic acid
      (STA) adsorbed on Ag(100) in acid solution. The voltammetry shows that STA
      passivates the Ag surface relative to electron transfer to a solution redox
      species. STM images reveal the formation of a series of lattice structures, one
      of which can be associated with a commensurate ( radical13x radical13)R33.69
      degrees structural model. X-ray reflectivity measurements show uniquely that STA
      orients with its four-fold axis perpendicular to the Ag(100) surface and that the
      center of the STA molecule is 4.90 A above the top layer of the Ag substrate.
      Analysis of bond lengths leads to a footprint of STA on Ag(100), in which the
      four terminal O atoms are located near the hollow sites and have a Ag-O bond
      length of 2.06 A. This bond length is consistent with a strong covalent
      interaction between STA and the Ag surface.

PMID- 11535092
TI  - Photochemical instability of CdSe nanocrystals coated by hydrophilic thiols.
AB  - The photochemical instability of CdSe nanocrystals coated by hydrophilic thiols
      was studied nondestructively and systematically in water. The results revealed
      that the photochemical instability of the nanocrystals actually included three
      distinguishable processes, namely the photocatalytic oxidation of the thiol
      ligands on the surface of nanocrystals, the photooxidation of the nanocrystals,
      and the precipitation of the nanocrystals. At first, the thiol ligands on the
      surface of a nanocrystal were gradually photocatalytically oxidized using the
      CdSe nanocrystal core as the photocatalyst. This photocatalytic oxidation process
      was observed as a zero-order reaction in terms of the concentration of the free
      thiols in the solution. The photogenerated holes in a nanocrystal were trapped
      onto the thiol ligands bound on the surface of the nanocrystal, which initiated
      the photooxidation of the ligands and protected the nanocrystal from any
      photooxidation. After nearly all of the thiol ligands on the surface of the
      nanocrystals were converted into disulfides, the system underwent several
      different pathways. If the disulfides were soluble in water, then all of the
      disulfides fell into the solution at the end of this initial process, and the
      nanocrystals precipitated out of the solution without much variation over their
      size and size distribution. When the disulfides were insoluble in water, they
      likely formed a micelle-like structure around the nanocrystal core and kept it
      soluble in the solution. In this case, the nanocrystals only precipitated after
      severe oxidation, which took a long period of time. If the system contained
      excess free thiol ligands, they replaced the photochemically generated disulfides
      and maintained the stability and solubility of the nanocrystals. The initiation
      stage of the photooxidation of CdSe nanocrystals themselves increased as the
      thickness and packing density of the ligand shell increased. This was explained
      by considering the ligand shell on the surface of a nanocrystal as the diffusion
      barrier of the oxygen species from the bulk solution into the interface between
      the nanocrystal and the surface ligands. Experimental results clearly indicated
      that the initiation stage of the photooxidation was not caused by the chemical
      oxidation of the system kept in air under dark conditions or the hydrolysis of
      the cadmium-thiol bonds on the surface of the nanocrystals, both of which were
      magnitudes slower than the photocatalytic oxidation of the surface ligands if
      they occurred at all. The results described in this contribution have already
      been applied for designing new types of thiol ligands which dramatically improved
      the photochemical stability of CdSe nanocrystals with a ligand shell that is as
      thin as approximately 1 nm.

PMID- 11535093
TI  - Stereoselective total synthesis of the cyanobacterial hepatotoxin 7
      epicylindrospermopsin: revision of the stereochemistry of cylindrospermopsin.

PMID- 11535094
TI  - Chemically induced spin transfer to an encased molecular cluster: an EPR study of
      Sc3N@C80 radical anions.

PMID- 11535095
TI  - Heterolytic and homolytic activation of dihydrogen at an unusual iridium (II)
      sulfide.

PMID- 11535096
TI  - A homodinuclear Cr(V)-Cr(V) complex forms from the chromate-glutathione reaction
      in water.

PMID- 11535097
TI  - Electrochemistry of CdS nanoparticles: a correlation between optical and
      electrochemical band gaps.

PMID- 11535098
TI  - An unusual ruthenium-catalyzed dimerization of propargyl alcohols.

PMID- 11535099
TI  - Catalytic solvent-free arsination: first catalytic application of Pd-Ar/As-Ph
      exchange in the syntheses of functionalized aryl arsines.

PMID- 11535100
TI  - Transferring a biosynthetic cycle into a productive Escherichia coli strain:
      large-scale synthesis of galactosides.

PMID- 11535101
TI  - S-N dissociation energies of S-nitrosothiols: on the origins of nitrosothiol
      decomposition rates.

PMID- 11535102
TI  - X-ray excited optical luminescence studies of tris-(2,2'-bipyridine)ruthenium(II)
      at the C, N K-edge and Ru L3,2-edge.

PMID- 11535103
TI  - A new synthesis of cyclobutanones: highly selective carbonylation of
      titanacyclobutane complexes prepared by free radical alkylation.

PMID- 11535104
TI  - Local dynamics of the CpG step in a DNA crystal.

PMID- 11535105
TI  - A new cyclic pseudopeptide receptor for Li+ from a dynamic combinatorial library.

PMID- 11535106
TI  - Chiral imidazolylidine ligands for asymmetric hydrogenation of aryl alkenes.

PMID- 11535107
TI  - PAF acetylhydrolase gene polymorphisms and asthma severity.
AB  - This review describes the current understanding of the contributions of genetic
      alterations in platelet-activating factor (PAF) acetylhydrolase to the
      pathogenesis of asthma. A variety of in vitro and in vivo studies, performed by
      multiple laboratories, suggest that the lipid substrates of this enzyme, PAF and
      oxidised derivatives of phosphatidylcholines, play important roles as causative
      factors in many diseases including asthma. PAF acetylhydrolase inactivates PAF
      and oxidatively-fragmented lipids thus providing a mechanism to prevent their pro
      inflammatory effects. Since it is a most unusual protein, the biochemical,
      structural and functional characteristics of PAF acetylhydrolase continue to be
      unravelled. First, the ability of this enzyme to inactivate pro-inflammatory
      lipid mediators is modulated by its association with lipoproteins and by its
      susceptibility to oxidative inactivation. Second, mediators of inflammation, such
      as the substrates for PAF acetylhydrolase, alter expression of the protein at the
      transcriptional level. Third, naturally-occurring variants of PAF acetylhydrolase
      have catalytic properties different from those exhibited by the most common form
      of this protein. Thus, a variety of factors, including genetics, contribute to
      determine the biological level of lipid substrates known to act as mediators of
      asthma and other diseases. Here, I summarise key studies that implicate PAF and
      related molecules as important mediators in the pathogenesis of asthma. Next, I
      describe clinical findings that are consistent with a role of PAF acetylhydrolase
      as a modulator of asthma. Third, I focus on the biochemical effects associated
      with naturally-occurring mutations and polymorphisms in the PAF acetylhydrolase
      gene and the incidence of these genetic variations in populations of asthmatic
      subjects. Finally, I present my views on the future of this emerging field and
      the potential utility of performing additional studies aimed at further
      characterising the contribution of PAF acetylhydrolase to the pathogenesis of a
      complex syndrome generally recognised as a multifactorial and heterogeneous
      disease.

PMID- 11535108
TI  - The pharmacogenetics of analgesia: toward a genetically-based approach to pain
      management.
AB  - Interindividual differences in the experience of pain have been appreciated
      clinically for over a century. More recently, there has been a growing body of
      evidence demonstrating differences in analgesic response to various
      pharmacotherapies, although the source of this variability largely remains to be
      explained. To this end, basic science research is beginning to identify the
      allelic variants that underlie such antinociceptive variability using a
      multiplicity of animal models, and powerful genetic approaches are being
      exploited to accelerate this process. Although the vast majority of these studies
      have focused on the pharmacogenetics of opioids, owing to their prominent status
      as analgesics, the number of pharmacotherapies evincing genetically-based
      variability is rapidly expanding. In addition, analogous studies have been
      undertaken in humans, as a small but growing number of clinical trials have begun
      to evaluate prospectively the existence, if oftentimes not the origin, of
      interindividual differences in analgesic drug response. Importantly, with a few
      notable exceptions, such efforts have primarily identified differences in
      analgesic efficacy and/or potency between male and female human subjects. Looking
      toward the future development of one or more widely utilised, pharmacogenetic
      screens that would lead to modifications in treatment planning, at least with
      respect to the pharmacologic management of pain, this review will document the
      breadth of genetically-based variability in drug-mediated antinociception in
      animals. Specific examples in which the gene or genes underlying such variability
      have been postulated or identified will be given, while highlighting the effect
      of sex and its interactions with other genetic backgrounds. Finally, we will
      summarise and evaluate the literature on pharmacogenetic differences in human
      analgesic drug response, for which the influence of sex has served as one of the
      better studied and heuristically insightful examples.

PMID- 11535109
TI  - Shifting paradigms in gene-mapping methodology for complex traits.
AB  - The analysis of genetic linkage has been highly successful in the mapping of the
      genes responsible for Mendelian diseases. In the past decade, attempts have been
      made to extend this approach to multifactorial disorders and other health-related
      traits. It has proved difficult, however, to obtain strong and replicable linkage
      findings for the common forms of heritable diseases. This, together with the
      rapid pace of development of molecular technology and expansion of genome
      sequence information, has resulted in significant shifts in research paradigm.
      There is an increasing recognition of the need to understand the population
      genetics and biometrical properties of clinically relevant traits so that
      phenotypes can be defined in such a way that maximises the chances of successful
      gene mapping. There is a trend towards systematic association analysis with
      increasing sophistication in the analysis of pooled DNA samples and multi-locus
      haplotypes, and in the use of unlinked background markers to protect against
      spurious associations. We can expect increasing integration between genetics,
      epidemiology and clinical trials leading to genetically informative designs that
      will not only identify susceptibility genes but also clarify how the environment
      influences their effects and how they may modify the response to therapeutic
      interventions.

PMID- 11535110
TI  - Genomics, complexity and drug discovery: insights from Boolean network models of
      cellular regulation.
AB  - The completion of the first draft of the human genome sequence has revived the
      old notion that there is no one-to-one mapping between genotype and phenotype. It
      is now becoming clear that to elucidate the fundamental principles that govern
      how genomic information translates into organismal complexity, we must overcome
      the current habit of ad hoc explanations and instead embrace novel, formal
      concepts that will involve computer modelling. Most modelling approaches aim at
      recreating a living system via computer simulation, by including as much details
      as possible. In contrast, the Boolean network model reviewed here represents an
      abstraction and a coarse-graining, such that it can serve as a simple, efficient
      tool for the extraction of the very basic design principles of molecular
      regulatory networks, without having to deal with all the biochemical details. We
      demonstrate here that such a discrete network model can help to examine how
      genome-wide molecular interactions generate the coherent, rule-like behaviour of
      a cell - the first level of integration in the multi-scale complexity of the
      living organism. Hereby the various cell fates, such as differentiation,
      proliferation and apoptosis, are treated as attractor states of the network. This
      modelling language allows us to integrate qualitative gene and protein
      interaction data to explain a series of hitherto non-intuitive cell behaviours.
      As the human genome project starts to reveal the limits of the current simplistic
      'one gene - one function - one target' paradigm, the development of conceptual
      tools to increase our understanding of how the intricate interplay of genes gives
      rise to a global 'biological observable' will open a new perspective for post
      genomic drug target discovery.

PMID- 11535111
TI  - Imaging neurochemical endophenotypes: promises and pitfalls.
AB  - A large number of polymorphisms in genes coding for neurotransmitter receptors
      and transporters have been associated with neuropsychiatric conditions, although
      few of these associations have been consistently replicated. These proteins are
      critical targets of psychoactive drugs and the clarification of the functional
      significance of these polymorphisms might offer important leads for drug
      development and therapeutic applications. Brain imaging techniques such as single
      photon emission computed tomography (SPECT) and positron emission tomography
      (PET) provide the means to monitor the expression and function of many of these
      proteins in the living human brain. This paper reviews brain imaging studies
      designed to evaluate the significance of polymorphisms in genes coding for
      important drug targets (e.g., the serotonin transporter [SERT], the dopamine
      transporter [DAT] and the dopamine D(2) receptor) in terms of expression or
      function. These studies illustrate the unique opportunities, as well as the
      pitfalls, generated by combining genetic analysis with brain imaging studies.

PMID- 11535112
TI  - Gene identification in Alzheimer's disease.
AB  - Alzheimer's disease (AD) is the most common cause of dementia in the elderly
      population. Three genes have been identified that cause the less common early
      onset, familial cases of the disease: the amyloid precursor (APP) protein gene on
      chromosome 21, the presenilin 1 (PSEN1) gene on chromosome 14 and the presenilin
      2 (PSEN2) gene on chromosome 1. Mutations in these genes account for << 2% of the
      total number of AD cases. More than 50% of the cases are late-onset and related
      to the apolipoprotein E (APOE) gene on chromosome 19. The apolipoprotein E locus
      is a susceptibility gene, with polymorphisms affecting both risk and age-of-onset
      of the disease. Intense efforts are underway to identify additional
      susceptibility genes and promising regions on chromosomes 6, 9, 10 and 12 have
      been identified through whole genome scans. In addition, the genetic basis of
      several other non-AD inherited dementias has been unravelled. Discovery of the
      genetically relevant genes will aid in the elucidation of the pathogenesis of AD.
      The high-throughput tools of pharmacogenomics for gene-to-function-to-target
      studies can provide a quicker means of monitoring how mutations and polymorphisms
      affect model systems' adaptations to the altered genes, possibly identifying
      signal transduction or biochemical pathways. This relevant information can then
      be used for drug target selection and pharmacogenetics.

PMID- 11535113
TI  - Dopamine receptor polymorphisms and drug response in schizophrenia.
AB  - The elucidation of the assumed genetic contribution to the predisposition towards
      schizophrenia is a scientifically challenging enterprise with considerable impact
      on therapeutic possibilities. A pharmacogenetic approach, targeted to the
      clinical response to medication, provides a promising alternative as a means of
      investigation, with the prospect of gaining knowledge about the disease and of
      developing an individually tailored medical treatment. This review will focus on
      dopamine receptor genes which have, due to the dopamine hypothesis of
      schizophrenia, been a prime target in pharmacogenetic studies of schizophrenia.
      The current status of the studies results will be displayed and future prospects
      will be discussed.

PMID- 11535114
TI  - CNS myelination and PLP gene dosage.
AB  - The phenomenon of gene dosage effects demonstrates that the mechanisms of some
      genetic diseases are best recognised at the genomic level. Classical gene
      mutation screening approaches utilising PCR are unsuccessful in unravelling the
      basis of disease because the gene sequence is unaltered and only the copy number
      is different. Techniques for detecting DNA dosage are required. Examples of
      haploinsufficiency and gene deletions are well documented, but increased gene
      dosage is also an important genetic mechanism in disorders involving myelin
      proteins in the central (CNS) and peripheral nervous system (PNS). Here we review
      the dosage effects and mutations of the proteolipid protein (PLP) gene that
      causes Pelizaeus-Merzbacher disease (PMD) and spastic paraplegia Type 2 (SPG2)
      disorders of CNS myelination. Similarities are drawn with the peripheral
      neuropathies Charcot-Marie-Tooth disease Type 1 (CMT1A) and hereditary neuropathy
      with liability to pressure palsies (HNPP) that are also caused by dosage effects
      and mutations in a single myelin protein gene (peripheral myelin protein 22, PMP
      22). We compare the different mutational mechanisms in man and analogous mouse
      models that suggest a function for PLP beyond its structural role in myelin. We
      focus on the increased dosage of the PLP gene that is the major cause of PMD and
      results from a submicroscopic duplication of Xq22. Other clinical phenotypes may
      arise from gene dosage imbalance with the potential effect of submicroscopic
      duplications and deletions of the genome being underestimated. Genome sequencing
      may identify intrinsic structural properties of the DNA with greater
      susceptibility to these rearrangements and thereby reflect structural changes in
      the genome.

PMID- 11535115
TI  - Prospects offered by genome studies for combating meningococcal disease by
      vaccination.
AB  - Meningococcal disease was first recognised and Neisseria meningitidis isolated as
      the causative agent over 100 years ago, but despite more than a century of
      research, attempts to eliminate this distressing illness have so far been
      thwarted. The main problem lies in the fact that N. meningitidis usually exists
      as a harmless commensal inhabitant of the human nasopharynx, the pathogenic state
      being the exception rather than the norm. As man is its only host, the
      meningococcus is uniquely adapted to this ecological niche and has evolved an
      array of mechanisms for evading clearance by the human immune response. Progress
      has been made in combating the disease by developing vaccines that target
      specific pathogenic serogroups of meningococci. However, a fully comprehensive
      vaccine that protects against all pathogenic strains is still just beyond reach.
      The publication of the genome sequences of two meningococcal strains, one each
      from serogroups A and B and the imminent completion of a third illustrates the
      extent of the problems to be overcome, namely the vast array of genetic
      mechanisms for the generation of meningococcal diversity. Fortunately, genome
      studies also provide new hope for solutions to these problems in the potential
      for a greater understanding of meningococcal pathogenesis and possibilities for
      the identification of new vaccine candidates. This review describes some of the
      approaches that are currently being used to exploit the information from
      meningococcal genome sequences and seeks to identify future prospects for
      combating meningococcal disease.

PMID- 11535116
TI  - Carbohydrate specificity of a galectin from chicken liver (CG-16).
AB  - Owing to the expression of more than one type of galectin in animal tissues, the
      delineation of the functions of individual members of this lectin family requires
      the precise definition of their carbohydrate specificities. Thus, the binding
      properties of chicken liver galectin (CG-16) to glycoproteins (gps) and
      Streptococcus pneumoniae type 14 polysaccharide were studied by the biotin/avidin
      mediated microtitre-plate lectin-binding assay and by the inhibition of lectin
      glycan interactions with sugar ligands. Among 33 glycans tested for lectin
      binding, CG-16 reacted best with human blood group ABO (H) precursor gps and
      their equivalent gps, which contain a high density of D-galactopyranose(beta1-4)2
      acetamido-2-deoxy-D-glucopyranose [Gal(beta1-4)GlcNAc] and Gal(beta1-3)GlcNAc
      residues at the non-reducing end, but this lectin reacted weakly or not at all
      with A-,H-type and sialylated gps. Among the oligosaccharides tested by the
      inhibition assay, the tri-antennary Gal(beta1-4)GlcNAc (Tri-II) was the best. It
      was 2.1x10(3) nM and 3.0 times more potent than Gal and Gal(beta1-4)GlcNAc
      (II)/Gal(beta1-3)GlcNAc(beta1-3)Gal(beta1-4)Glc (lacto-N-tetraose) respectively.
      CG-16 has a preference for the beta-anomer of Gal at the non-reducing end of
      oligosaccharides with a Gal(beta1-4) linkage >Gal(beta1-3)> or =Gal(beta1-6).
      From the results, it can be concluded that the combining site of this agglutinin
      should be a cavity type, and that a hydrophobic interaction in the vicinity of
      the binding site for sugar accommodation increases the affinity. The binding site
      of CG-16 is as large as a tetrasaccharide of the beta-anomer of Gal, and is most
      complementary to lacto-N-tetraose and Gal(beta1-4)GlcNAc related sequences.

PMID- 11535117
TI  - Human glycosaminoglycan glucuronyltransferase I gene and a related processed
      pseudogene: genomic structure, chromosomal mapping and characterization.
AB  - Here we describe the characterization of the human glycosaminoglycan
      glucuronyltransferase I gene (GlcAT-I) and a related pseudogene. The GlcAT-I gene
      was localized to human chromosome 11q12-q13 by in situ hybridization of metaphase
      chromosomes. GlcAT-I spanned 7 kb of human genomic DNA and was divided into five
      exons. Northern blot analysis showed that GlcAT-I exhibited ubiquitous but
      markedly different expressions in the human tissues examined. The GlcAT-I
      promoter was approx. 3-fold more active in a melanoma cell line than in a
      hepatoma cell line, providing evidence for the differential regulation of the
      gene's expression. Stepwise 5' deletions of the promoter identified a strong
      enhancer element between -303 and -153 bp that included binding motifs for Ets,
      CREB (cAMP-response-element-binding protein) and STAT (signal transducers and
      activators of transcription). Screening of a human genomic library identified one
      additional distinct genomic clone containing an approx. 1.4 kb sequence region
      that shared an overall 95.3% nucleotide identity with exons 1-5 of GlcAT-I.
      However, a lack of intron sequences, as well as the presence of several
      nucleotide mutations, insertions and deletions that disrupted the potential GlcAT
      I reading frame, suggested that the clone contained a processed pseudogene. The
      pseudogene was localized to chromosome 3. The human genome therefore contains two
      related GlcAT-I genes that are located on separate chromosomes.

PMID- 11535118
TI  - Flavonoids protect neurons from oxidized low-density-lipoprotein-induced
      apoptosis involving c-Jun N-terminal kinase (JNK), c-Jun and caspase-3.
AB  - Oxidative stress has been associated with neuronal loss in neurodegenerative
      diseases and during age-associated cognitive decline. Flavonoids have been
      proposed to play a useful role in protecting the central nervous system against
      oxidative and excitotoxic stress, although the mechanism of action is unknown.
      Using oxidized low-density lipoprotein (oxLDL) as the oxidative insult we
      investigated the mechanism of neurotoxicity and attempted to identify possible
      sites of action of two of the most potent protective flavonoids, epicatechin and
      kaempferol, in cultured primary neurons. Using cultured striatal neurons and
      selective phosphospecific antibodies we addressed the potential role of
      extracellular signal-regulated kinases 1/2 (ERK1/2) and c-Jun N-terminal kinase
      (JNK). OxLDL stimulated a Ca(2+)-dependent activation of both ERK1/2 and JNK that
      was strongly inhibited by pre-treatment with low micromolar concentrations of
      epicatechin. Neurotoxicity induced by oxLDL, however, was neither reduced nor
      enhanced by inhibiting ERK1/2 activation with mitogen-activated protein kinase
      kinase (MEK) inhibitors, suggesting that this cascade is unlikely to be involved
      in either oxLDL toxicity or the protective effects of flavonoids. oxLDL caused a
      sustained activation of JNK that resulted in the phosphorylation of the
      transcription factor c-Jun, which was abolished in neurons pre-treated with
      flavonoids. Furthermore, oxLDL induced the cleavage of procaspase-3 and increased
      caspase-3-like protease activity in neurons, an effect which was strongly
      inhibited by pre-exposure to either epicatechin or kaempferol. In addition, a
      caspase-3 inhibitor reduced oxLDL-induced neuronal death, implicating an
      apoptotic mechanism. A major in vivo metabolite of epicatechin, 3'-O-methyl
      epicatechin was as effective as epicatechin in protecting neurons. Thus dietary
      flavonoids might have potential as protective agents against neuronal apoptosis
      through selective actions within stress-activated cellular responses, including
      protein kinase signalling cascades.

PMID- 11535119
TI  - All three splice variants of the human sarco/endoplasmic reticulum Ca2+-ATPase 3
      gene are translated to proteins: a study of their co-expression in platelets and
      lymphoid cells.
AB  - The molecular cloning of two previously unknown human sarco/endoplasmic reticulum
      Ca(2+)-ATPase 3 (SERCA3) 3'-end transcripts, 3b and 3c, has been recently
      published. Data were lacking, however, for the presence of these SERCA3 variants
      in different tissue or cell types at the protein level. Here we report the co
      expression of three human SERCA3 protein isoforms in platelets and T lymphoid
      Jurkat cells. Isoform-specific polyclonal anti-peptide antibodies have been
      generated that recognize specifically the SERCA3a, 3b or 3c splice variants at
      their C-termini, and this has been confirmed by peptide-competition experiments
      as well. None of these antibodies cross-reacted with the housekeeping SERCA2b
      isoform co-expressed endogenously with SERCA3 proteins in non-muscle cells.
      Although all three SERCA3 isoforms could be detected in platelets, the 3a form
      was the most abundantly expressed species. Its size matched the apparent size of
      SERCA3a over-expressed in HEK-293 cells. Immunoprecipitation of the SERCA3
      variants from platelet membranes using a PL/IM 430-affinity matrix provided
      evidence that the putative pan-anti-SERCA3 antibody, PL/IM 430, recognizes all
      SERCA3 protein isoforms. The epitope for the PL/IM 430 antibody could be
      localized in a 40 kDa N-terminal tryptic fragment common to all three SERCA3
      variants. Comparative Western-blot analysis showed that the expression level of
      the SERCA3a, 3b and 3c isoforms was more than 10 times lower in Jurkat cells than
      in platelets, whereas expression of the ubiquitous SERCA2b was nearly identical.
      This work highlights new Ca(2+)-transporting proteins of haematopoietic cells and
      provides specific antibodies for their detection.

PMID- 11535120
TI  - Lactate supply as a determinant of the distribution of intracellular pH within
      the hepatic lobule.
AB  - When isolated livers from starved rats are perfused with lactate at constant
      perfusate pH and P(co(2)), there is a marked gradient of cell pH (pH(i)) along
      the length of the lobular radius, with periportal cells being substantially more
      alkaline than perivenous cells. In the present studies, the perivenous 21% of the
      lobular volume was destroyed by retrograde digitonin perfusion, and antegrade
      perfusion restored. pH(i) was determined by (31)P-NMR. The remaining periportal
      cells, the site of gluconeogenesis from lactate, had a substantially higher mean
      pH(i) (7.42) than did the intact liver (7.23). When lactate was removed from the
      perfusate, mean pH(i) decreased to 7.25. The corresponding concentration of cell
      bicarbonate fell with a half-time of approximately 5 min. When lactate was re
      introduced mean pH(i) rose to 7.34. We conclude that a major contributor to
      periportal alkalinity under these conditions is proton consumption during
      gluconeogenesis from lactate ions.

PMID- 11535121
TI  - Pseudomonas cellulosa expresses a single membrane-bound glycoside hydrolase
      family 51 arabinofuranosidase.
AB  - In the accompanying paper [Beylot, McKie, Voragen, Doeswijk-Voragen and Gilbert
      (2001) Biochem. J. 358, 607-614] the chromosome of Pseudomonas cellulosa was
      shown to contain two genes, abf51A and abf62A, that encode arabinofuranosidases
      belonging to glycoside hydrolase families 51 and 62, respectively. In this report
      we show that expression of Abf51A is induced by arabinose and arabinose
      containing polysaccharides. Northern-blot analysis showed that abf51A was
      efficiently transcribed, whereas no transcript derived from abf62A was detected
      in the presence of arabinose-containing polysaccharides. Zymogram and Western
      blot analyses revealed that Abf51A was located on the outer membrane of P.
      cellulosa. To investigate the importance of Abf51A in the release of arabinose
      from poly- and oligosaccharides, transposon mutagenesis was used to construct an
      abf51A-inactive mutant of P. cellulosa (Deltaabf51A). The mutant did not grow on
      linear arabinan or sugar beet arabinan, and utilized arabinoxylan much more
      slowly than the wild-type bacterium. Arabinofuranosidase activity in Deltaabf51A
      against aryl-alpha-arabinofuranosides, arabinan and alpha1,5-linked arabino
      oligosaccharides was approx. 1% of the wild-type bacterium. The mutant bacterium
      did not exhibit arabinofuranosidase activity against arabinoxylan, supporting the
      view that abf62A is not expressed in P. cellulosa. These data indicate that P.
      cellulosa expresses a membrane-bound glycoside hydrolase family 51
      arabinofuranosidase that plays a pivotal role in releasing arabinose from
      polysaccharides and arabino-oligosaccharides.

PMID- 11535122
TI  - The Pseudomonas cellulosa glycoside hydrolase family 51 arabinofuranosidase
      exhibits wide substrate specificity.
AB  - To investigate the mechanism by which Pseudomonas cellulosa releases arabinose
      from polysaccharides and oligosaccharides, a gene library of P. cellulosa genomic
      DNA was screened for 4-methylumbelliferyl-alpha-L-arabinofuranosidase (MUAase)
      activity. A single MUAase gene (abf51A) was isolated, which encoded a non-modular
      glycoside hydrolase family (GH) 51 arabinofuranosidase (Abf51A) of 57000 Da. The
      substrate specificity of the Abf51A showed that it preferentially removed
      alpha1,2- and alpha1,3-linked arabinofuranose side chains from either arabinan or
      arabinoxylan, and hydrolysed alpha1,5-linked arabino-oligosaccharides, although
      at a much lower rate. The activity of Abf51A against arabinoxylan was similar to
      a GH62 arabinofuranosidase encoded by a P. cellulosa gene. Glu-194 and Glu-321 of
      Abf51A are conserved in GH51 enzymes, and it has been suggested that these amino
      acids comprise the key catalytic acid/base and nucleophile residues,
      respectively. To evaluate this hypothesis the biochemical properties of E194A and
      E321A mutants of Abf51A were evaluated. The data were consistent with the view
      that Glu-194 and Glu-321 comprise the key catalytic residues of Abf51A. These
      data, in conjunction with the results presented in the accompanying paper
      [Beylot, Emami, McKie, Gilbert and Pell (2001) Biochem. J. 358, 599-605],
      indicate that P. cellulosa expresses a membrane-bound GH51 arabinofuranosidase
      that plays a pivotal role in releasing arabinose from a range of polysaccharides
      and oligosaccharides.

PMID- 11535123
TI  - Analysis of aggrecan in human knee cartilage and synovial fluid indicates that
      aggrecanase (ADAMTS) activity is responsible for the catabolic turnover and loss
      of whole aggrecan whereas other protease activity is required for C-terminal
      processing in vivo.
AB  - Studies of aggrecan proteolysis in human joints have implicated both the
      aggrecanase [ADAMTS, a disintegrin-like and metalloprotease (reprolysin-type)
      with thrombospondin type 1 motif] and matrix metalloproteinase (MMP) families. We
      have analysed the aggrecan core protein species present in vivo in both articular
      cartilage and synovial fluids from normal, acutely injured and osteoarthritic
      joints. Normal cartilage contains at least seven major G1 domain (the N-terminal
      globular domain of aggrecan)-bearing species, of which three (full-length core,
      G1-NITEGE(373) and G1-VDIPEN(341)) have been identified. The C-terminals of the
      others are unknown but digestion of fetal human aggrecan with MMP-3 and crude
      aggrecanase suggests that they are products of MMP-like activity in vivo. Normal
      synovial fluids contain at least 10 species, of which nine result from ADAMTS
      dependent cleavage, and this cleavage occurs at all of the five known aggrecanase
      sites. Aggrecan fragments in the cartilage and synovial fluids of acutely injured
      joints are generally similar to normal, but all contain a markedly increased
      ratio of G1-NITEGE to G1-VDIPEN. Aggrecan from the cartilage of late-stage
      osteoarthritis patients is remarkably similar to normal, whereas the synovial
      fluid aggrecan is more fragmented than that from normal or injured knees. The
      analyses suggest that the role of the ADAMTS and these MMP-like activities in
      human cartilage are distinctly different. Excessive ADAMTS activity in vivo is
      destructive to cartilage matrix, since the bulk of the glycosaminoglycan (GAG)
      bearing products are released from the tissue into the synovial fluid following
      cleavage of the Glu(373)-Ala(374) bond. In contrast, the MMP-like activity
      appears to be essentially non-destructive, since much of the GAG-bearing product
      is retained in the tissue following cleavages that are in the more C-terminal
      regions of the molecule.

PMID- 11535124
TI  - Dimethyl sulphoxide enhances the effects of P(i) in myofibrils and inhibits the
      activity of rabbit skeletal muscle contractile proteins.
AB  - In the catalytic cycle of skeletal muscle, myosin alternates between strongly and
      weakly bound cross-bridges, with the latter contributing little to sustained
      tension. Here we describe the action of DMSO, an organic solvent that appears to
      increase the population of weakly bound cross-bridges that accumulate after the
      binding of ATP, but before P(i) release. DMSO (5-30%, v/v) reversibly inhibits
      tension and ATP hydrolysis in vertebrate skeletal muscle myofibrils, and
      decreases the speed of unregulated F-actin in an in vitro motility assay with
      heavy meromyosin. In solution, controls for enzyme activity and intrinsic
      tryptophan fluorescence of myosin subfragment 1 (S1) in the presence of different
      cations indicate that structural changes attributable to DMSO are small and
      reversible, and do not involve unfolding. Since DMSO depresses S1 and acto-S1
      MgATPase activities in the same proportions, without altering acto-S1 affinity,
      the principal DMSO target apparently lies within the catalytic cycle rather than
      with actin-myosin binding. Inhibition by DMSO in myofibrils is the same in the
      presence or the absence of Ca(2+) and regulatory proteins, in contrast with the
      effects of ethylene glycol, and the Ca(2+) sensitivity of isometric tension is
      slightly decreased by DMSO. The apparent affinity for P(i) is enhanced markedly
      by DMSO (and to a lesser extent by ethylene glycol) in skinned fibres, suggesting
      that DMSO stabilizes cross-bridges that have ADP.P(i) or ATP bound to them.

PMID- 11535126
TI  - Cloning and characterization of the pseudonajatoxin b precursor.
AB  - An Australian common brown snake, Pseudonaja textilis, is known to contain highly
      lethal neurotoxins. Among them, a long-chain alpha-neurotoxin, pseudonajatoxin b,
      has been identified. In this report, while presenting evidence for the presence
      of at least four such long-chain alpha-neurotoxins in the venom of P. textilis,
      we describe the characteristics of both the mRNA and the gene responsible for the
      synthesis of these neurotoxins. A precursor toxin synthesized from the gene has
      been identified as being capable of producing the isoforms possibly by post
      translational modifications at its C-terminal end. Recombinant toxins
      corresponding to the precursor and its product have been found to possess similar
      binding affinities for muscular acetylcholine receptors (IC(50)=3x10(-8) M) and a
      lethality, LD(50), of 0.15 microg/g in mice.

PMID- 11535125
TI  - Pulmonary lipid phosphate phosphohydrolase in plasma membrane signalling
      platforms.
AB  - Lipid phosphate phosphohydrolase (LPP) has recently been proposed to have roles
      in signal transduction, acting sequentially to phospholipase D (PLD) and in
      attenuating the effects of phospholipid growth factors on cellular proliferation.
      In this study, LPP activity is reported to be enriched in lipid-rich signalling
      platforms isolated from rat lung tissue, isolated rat type II cells and type II
      cell-mouse lung epithelial cell lines (MLE12 and MLE15). Lung and cell line
      caveolin-enriched domains (CEDs), prepared on the basis of their detergent
      insolubility in Triton X-100, contain caveolin-1 and protein kinase C isoforms.
      The LPP3 isoform was predominantly localized to rat lung CEDs. These lipid-rich
      domains, including those from isolated rat type II cells, were enriched both in
      phosphatidylcholine plus sphingomyelin (PC+SM) and cholesterol. Saponin treatment
      of MLE15 cells shifted the LPP activity, cholesterol, PC+SM and caveolin-1 from
      lipid microdomains to detergent-soluble fractions. Elevated LPP activity and
      LPP1/1a protein are present in caveolae from MLE15 cells prepared using the
      cationic-colloidal-silica method. In contrast, total plasma membranes had a
      higher abundance of LPP1/1a protein with low LPP activity. Phorbol ester
      treatment caused a 3.8-fold increase in LPP specific activity in MLE12 CEDs. Thus
      the activated form of LPP1/1a may be recruited into caveolae/rafts.
      Transdifferentiation of type II cells into a type I-like cell demonstrated
      enrichment in caveolin-1 levels and LPP activity. These results indicate that LPP
      is localized in caveolae and/or rafts in lung tissue, isolated type II cells and
      type II cell lines and is consistent with a role for LPP in both caveolae/raft
      signalling and caveolar dynamics.

PMID- 11535127
TI  - Fatty acid and amino acid modulation of glucose cycling in isolated rat
      hepatocytes.
AB  - We studied the influence of glucose/glucose 6-phosphate cycling on glycogen
      deposition from glucose in fasted-rat hepatocytes using S4048 and CP320626,
      specific inhibitors of glucose-6-phosphate translocase and glycogen phosphorylase
      respectively. The effect of amino acids and oleate was also examined. The
      following observations were made: (1) with glucose alone, net glycogen production
      was low. Inhibition of glucose-6-phosphate translocase increased intracellular
      glucose 6-phosphate (3-fold), glycogen accumulation (5-fold) without change in
      active (dephosphorylated) glycogen synthase (GSa) activity, and lactate
      production (4-fold). With both glucose 6-phosphate translocase and glycogen
      phosphorylase inhibited, glycogen deposition increased 8-fold and approached
      reported in vivo rates of glycogen deposition during the fasted-->fed transition.
      Addition of a physiological mixture of amino acids in the presence of glucose
      increased glycogen accumulation (4-fold) through activation of GS and inhibition
      of glucose-6-phosphatase flux. Addition of oleate with glucose present decreased
      glycolytic flux and increased the flux through glucose 6-phosphatase with no
      change in glycogen deposition. With glucose 6-phosphate translocase inhibited by
      S4048, oleate increased intracellular glucose 6-phosphate (3-fold) and net
      glycogen production (1.5-fold), without a major change in GSa activity. It is
      concluded that glucose cycling in hepatocytes prevents the net accumulation of
      glycogen from glucose. Amino acids activate GS and inhibit flux through glucose-6
      phosphatase, while oleate inhibits glycolysis and stimulates glucose-6
      phosphatase flux. Variation in glucose 6-phosphate does not always result in
      activity changes of GSa. Activation of glucose 6-phosphatase flux by fatty acids
      may contribute to the increased hepatic glucose production as seen in Type 2
      diabetes.

PMID- 11535128
TI  - Urokinase-catalysed cleavage of the urokinase receptor requires an intact
      glycolipid anchor.
AB  - Urokinase (uPA) has the striking ability to cleave its receptor, uPAR, thereby
      inactivating the binding potential of this molecule. Here we demonstrate that the
      glycosylphosphatidylinositol (GPI) anchor of uPAR, which is attached to the third
      domain, is an important determinant in governing this reaction, even though the
      actual cleavage occurs between the first and second domains. Purified full-length
      GPI-anchored uPAR (GPI-uPAR) proved much more susceptible to uPA-mediated
      cleavage than recombinant truncated soluble uPAR (suPAR), which lacks the
      glycolipid anchor. This was not a general difference in proteolytic
      susceptibility since GPI-uPAR and suPAR were cleaved with equal efficiency by
      plasmin. Since the amino acid sequences of GPI-uPAR and suPAR are identical
      except for the C-terminal truncation, the different cleavage patterns suggest
      that the two uPAR variants differ in the conformation or the flexibility of the
      linker region between domains 1 and 2. This was supported by the fact that an
      antibody to the peptide AVTYSRSRYLE, amino acids 84-94 in the linker region,
      recognizes GPI-uPAR but not suPAR. This difference in the linker region is thus
      caused by a difference in a remote hydrophobic region. In accordance with this
      model, when the hydrophobic lipid moiety was removed from the glycolipid anchor
      by phospholipase C, low concentrations of uPA could no longer cleave the modified
      GPI-uPAR and the reactivity to the peptide antibody was greatly decreased.
      Naturally occurring suPAR, purified from plasma, was found to have a similar
      resistance to uPA cleavage as phospholipase C-treated GPI-uPAR and recombinant
      suPAR.

PMID- 11535129
TI  - Parameters affecting in vitro oxidation/folding of maurotoxin, a four-disulphide
      bridged scorpion toxin.
AB  - Maurotoxin (MTX) is a 34-mer scorpion toxin cross-linked by four disulphide
      bridges that acts on various K(+) channel subtypes. MTX adopts a disulphide
      bridge organization of the type C1-C5, C2-C6, C3-C4 and C7-C8, and folds
      according to the common alpha/beta scaffold reported for other known scorpion
      toxins. Here we have investigated the process and kinetics of the in vitro
      oxidation/folding of reduced synthetic L-MTX (L-sMTX, where L-MTX contains only L
      amino acid residues). During the oxidation/folding of reduced L-sMTX, the
      oxidation intermediates were blocked by iodoacetamide alkylation of free cysteine
      residues, and analysed by MS. The L-sMTX intermediates appeared sequentially over
      time from the least (intermediates with one disulphide bridge) to the most
      oxidized species (native-like, four-disulphide-bridged L-sMTX). The mathematical
      formulation of the diffusion-collision model being inadequate to accurately
      describe the kinetics of oxidation/folding of L-sMTX, we have formulated a
      derived mathematical description that better fits the experimental data. Using
      this mathematical description, we have compared for the first time the
      oxidation/folding of L-sMTX with that of D-sMTX, its stereoisomer that contains
      only D-amino acid residues. Several experimental parameters, likely to affect the
      oxidation/folding process, were studied further; these included temperature, pH,
      ionic strength, redox potential and concentration of reduced toxin. We also
      assessed the effects of some cellular enzymes, peptidylprolyl cis-trans isomerase
      (PPIase) and protein disulphide isomerase (PDI), on the folding pathways of
      reduced L-sMTX and D-sMTX. All the parameters tested affect the oxidative folding
      of sMTX, and the kinetics of this process were indistinguishable for L-sMTX and D
      sMTX, except when stereospecific enzymes were used. The most efficient conditions
      were found to be: 50 mM Tris/HCl/1.4 mM EDTA, pH 7.5, supplemented by 0.5 mM
      PPIase and 50 units/ml PDI for 0.1 mM reduced compound. These data represent the
      first report of potent stereoselective effects of cellular enzymes on the
      oxidation/folding of a scorpion toxin.

PMID- 11535130
TI  - Molecular events involved in up-regulating human Na+-independent neutral amino
      acid transporter LAT1 during T-cell activation.
AB  - We investigated the regulation of system-L amino acid transporter (LAT1) during T
      cell activation. In quiescent T-cells, L-leucine transport is mediated mainly by
      the system-L amino acid transport system and is increased significantly during T
      cell activation by PMA and ionomycin. In quiescent T-cells, the LAT1 protein was
      heterocomplexed with 4F2 heavy chain (4F2hc) in the plasma membrane. During T
      cell activation, the amounts of 4F2hc and LAT1 heterocomplex were significantly
      elevated compared with those in quiescent T-cells. In addition, by Northern-blot
      analysis, these increments were found to be due to elevated levels of LAT1 and
      4F2hc mRNA. Transient expression of constructs comprising various LAT1 gene
      promoter fragments, which contained all three of the GC boxes, was sufficient for
      promoting luciferase expression in Jurkat T-cells, but the promoter of the LAT1
      gene did not respond to PMA and ionomycin. Similar observations were observed in
      the human 4F2hc gene promoter. In nuclear run-on assay, the LAT1 and 4F2hc genes
      were actively transcribed even in quiescent T-cells, but the low levels of both
      transcripts were shown to be the result of a block to transcription elongation
      within the exon 1 intron 1 regions. These findings indicated that a removal of
      the block to mRNA elongation stimulates the induction of system-L amino acid
      transporter gene transcripts (LAT1 and 4F2hc) in activated T-cells.

PMID- 11535131
TI  - Targeting of the transcription factor Max during apoptosis: phosphorylation
      regulated cleavage by caspase-5 at an unusual glutamic acid residue in position
      P1.
AB  - Max is the central component of the Myc/Max/Mad network of transcription factors
      that regulate growth, differentiation and apoptosis. Whereas the Myc and Mad
      genes and proteins are highly regulated, Max expression is constitutive and no
      post-translational regulation is known. We have found that Max is targeted during
      Fas-induced apoptosis. Max is first dephosphorylated and subsequently cleaved by
      caspases. Two specific cleavage sites for caspases in Max were identified, one at
      IEVE(10) decreasing S and one at SAFD(135) decreasing G near the C-terminus,
      which are cleaved in vitro by caspase-5 and caspase-7 respectively. Mutational
      analysis indicates that both sites are also used in vivo. Thus Max represents the
      first caspase-5 substrate. The unusual cleavage after a glutamic acid residue is
      observed only with full-length, DNA-binding competent Max protein but not with
      corresponding peptides, suggesting that structural determinants might be
      important for this activity. Furthermore, cleavage by caspase-5 is inhibited by
      the protein kinase CK2-mediated phosphorylation of Max at Ser-11, a previously
      mapped phosphorylation site in vivo. These findings suggest that Fas-mediated
      dephosphorylation of Max is required for cleavage by caspase-5. The modifications
      that occur on Max in response to Fas signalling affect the DNA-binding activity
      of Max/Max homodimers. Taken together, our findings uncover three distinct
      processes, namely dephosphorylation and cleavage by caspase-5 and caspase-7, that
      target Max during Fas-mediated apoptosis, suggesting the regulation of the
      Myc/Max/Mad network through its central component.

PMID- 11535132
TI  - A diacylglycerol-activated Ca2+ channel in PC12 cells (an adrenal chromaffin cell
      line) correlates with expression of the TRP-6 (transient receptor potential)
      protein.
AB  - The structures, and mechanisms of activation, of plasma membrane intracellular
      messenger-activated, non-selective cation channels in animal cells are not well
      understood. The PC12 adrenal chromaffin cell line is a well-characterized example
      of a nerve cell. In PC12 cells, 1-oleolyl-2-acetyl-sn-glycerol (OAG), a membrane
      permeant analogue of diacylglycerol, initiated the inflow of Ca(2+), Mn(2+) and
      Sr(2+). Acetylcholine and thapsigargin initiated the inflow of Ca(2+) and Mn(2+),
      but not of Sr(2+). The activation of bivalent cation inflow by OAG: (i) was
      mimicked by another membrane-permeant diacylglycerol analogue, 1,2-dioctanoyl-sn
      glycerol, but not by the membrane-impermeant analogue 1-stearoyl-2-arachidonyl-sn
      glycerol; (ii) was not blocked by staurosporin or chelerythrine, inhibitors of
      protein kinase C; (iii) was enhanced by RHC80267 and R50922, inhibitors of
      diacylglycerol lipase and diacylglycerol kinase respectively; and (iv) was
      inhibited by extracellular Ca(2+). When OAG was added after acetylcholine, the
      effect of OAG on Ca(2+) inflow was over-and-above that induced by acetylcholine.
      2-Aminoethyl diphenylborate (2-APB) inhibited Ca(2+) inflow initiated by either
      acetylcholine or thapsigargin, but not that initiated by OAG. Flufenamic acid
      inhibited OAG-initiated, but not acetylcholine-initiated, Ca(2+) and Mn(2+)
      inflow. OAG-initiated Ca(2+) inflow was less sensitive to inhibition by SK&F96365
      than acetylcholine-initiated Ca(2+) inflow. In polyadenylated RNA prepared from
      PC12 cells, mRNA encoding TRP (transient receptor potential) proteins 1-6 was
      detected by reverse transcriptase (RT)-PCR, and in lysates of PC12 cells the
      endogenous TRP-6 protein was detected by Western blot analysis. It is concluded
      that PC12 cells express a diacylglycerol-activated, non-selective cation channel.
      Expression of this channel function correlates with expression of the TRP-3 and
      TRP-6 proteins, which have been shown previously to be activated by
      diacylglycerol when expressed heterologously in animal cells [Hofmann, Obukhov,
      Schaefer, Harteneck, Gudermann, and Schultz (1999) Nature (London) 397, 259-263].

PMID- 11535133
TI  - Binding of the merlin-I product of the neurofibromatosis type 2 tumour suppressor
      gene to a novel site in beta-fodrin is regulated by association between merlin
      domains.
AB  - The mechanism underlying the tumour-suppressor activity of the neurofibromatosis
      type 2 (NF2) gene product, merlin, is largely undefined but there is evidence
      that the biological function of the protein might be mediated partly through
      interactions with the cytoskeleton. Merlin is expressed predominantly as two
      isoforms that differ at their C-termini owing to alternative splicing of exon 16.
      By expressing merlin isoform I as bait in a yeast two-hybrid screen, we isolated
      a clone encoding a region of the cytoskeletal protein beta-fodrin. Confirmation
      of the merlin-fodrin interaction was provided by using the mammalian two-hybrid
      system and binding assays in vitro. In addition, these assays and co
      immunoprecipitation from mammalian cells revealed that the binding site for
      fodrin is located in the C-terminal half of merlin at a site that is masked in
      the native protein. Co-expression of the N-terminus of merlin decreased the
      interaction of its C-terminus with fodrin, implicating homophilic interactions of
      merlin isoform I in masking the fodrin-binding site. The effect of three disease
      associated mutations on the merlin-fodrin interaction and merlin dimerization was
      also investigated. The mutation L535P, but not L360P or K413E, significantly
      decreased the merlin-fodrin interaction but not dimerization, indicating that the
      tumour suppressor ability of merlin might reside partly in its ability to
      interact with the cytoskeleton via fodrin.

PMID- 11535134
TI  - Multimerization of monocyte chemoattractant protein-1 is not required for
      glycosaminoglycan-dependent transendothelial chemotaxis.
AB  - Chemokines interact with specific G-protein-coupled cell-surface receptors and
      with glycosaminoglycans (GAGs), such as heparan sulphate. Although chemokines
      often form multimers in solution, this process may be enhanced following
      interaction with GAGs on the cell surface, or within the extracellular matrix.
      However, the significance of multimerization for chemokine function remains
      controversial. In the present study, a fusion protein was prepared between the
      prototypical human CC chemokine, monocyte chemoattractant protein-1 (MCP-1; also
      known as CCL-2) and a large secreted placental alkaline phosphatase (SEAP)
      moiety. This fusion protein (MCP-1-SEAP) remained monomeric under conditions that
      promote oligomerization of the native chemokine. Radioligand binding showed that
      both native MCP-1 and MCP-1-SEAP competed for the same site on the surface of HEK
      293 cells expressing the CCR2b chemokine receptor. The interaction between either
      chemokine species and endothelial cell surface GAGs was antagonized by the
      addition of the heparan sulphate-like molecule, heparin. Both MCP-1 and MCP-1
      SEAP induced a Ca(2+)-flux in the THP-1 monocytic cell line, and were equally
      effective at promoting transendothelial chemotaxis of mononuclear immune cells,
      with maximal migration being produced by treatment with 12 nM of either species.
      In each case this chemotactic response was almost completely antagonized by the
      addition of heparin. The importance of interaction between either native MCP-1 or
      MCP-1-SEAP and cell-surface GAGs for transcellular migration was demonstrated by
      the almost complete absence of leucocyte chemotaxis across monolayers of GAG
      deficient mutant cells. In summary, this study shows that multimerization is
      neither necessary for, nor potentiates, the biological activity of MCP-1.
      However, the results do clearly demonstrate the importance of the interaction
      between MCP-1 and cell-surface heparan sulphate for transmonolayer leucocyte
      chemotaxis.

PMID- 11535135
TI  - Molecular cloning, gene organization and expression of rainbow trout
      (Oncorhynchus mykiss) inducible nitric oxide synthase (iNOS) gene.
AB  - A full-length inducible nitric oxide synthase (iNOS) gene has been sequenced for
      the first time outside the mammals, and the gene organization compared with that
      already determined for human iNOS. While there are some differences from the
      human gene, overall the exons show remarkable conservation in sequence and
      organization. As in human, the trout iNOS gene has 27 exons, with 18 of the trout
      exons being identical in size with the equivalent human exons. The cofactor
      binding domains are found in the same exons and in some cases are absolutely
      conserved. Differences include the start of the ORF in exon 3 instead of exon 2,
      resulting in a deletion at the 5' end of the trout iNOS protein. Exon 27 also
      shows a large difference in size and although the trout exon is larger this is
      due to the length of the 3'-UTR. Several non-mammalian features are notable, and
      include a conserved potential glycosylation site in chicken and fish, and an
      insertion at the boundary of exons 20 and 21 in fish. The intron sizes in trout
      were generally much smaller than in human iNOS, making the trout iNOS gene
      approximately half the size of the human gene. Analysis of RNA secondary
      structure revealed two regions with complementarity, which could interfere with
      reverse transcription. Using a trout fibroblast cell line (RTG-2 cells), it was
      shown by reverse transcriptase (RT)-PCR that virus infection was a good inducer
      of iNOS expression. However, when using a combination of Superscripttrade mark II
      for reverse transcription and primers at the 5' end of the gene only very weak
      products were amplified, in contrast with the situation when primers at the 3'
      end of the gene were used, or ThermoScripttrade mark-derived cDNA was used. The
      impact of such results on RT-PCR analysis of iNOS expression in trout is
      discussed.

PMID- 11535136
TI  - Four Trypanosoma brucei fatty acyl-CoA synthetases: fatty acid specificity of the
      recombinant proteins.
AB  - As part of our investigation of fatty acid metabolism in Trypanosoma brucei, we
      have expressed four acyl-CoA synthetase (TbACS) genes in Esherichia coli. The
      recombinant proteins, with His-tags on their C-termini, were purified to near
      homogeneity using nickel-chelate affinity chromatography. Although these enzymes
      are highly homologous, they have distinct specificities for fatty acid chain
      length. TbACS1 prefers saturated fatty acids in the range C(11:0) to C(14:0) and
      TbACS2 prefers shorter fatty acids, mainly C(10:0). TbACS3 and 4, which have 95%
      sequence identity, have similar specificities, favouring fatty acids between
      C(14:0) and C(17:0). In addition, TbACS1, 3 and 4 function well with a variety of
      unsaturated fatty acids.

PMID- 11535137
TI  - Human mucin gene MUC5AC: organization of its 5'-region and central repetitive
      region.
AB  - Human mucin gene MUC5AC is clustered with MUC2, MUC5B and MUC6 on chromosome
      11p15.5. We report here the full length cDNA sequence upstream of the repetitive
      region of human MUC5AC. We have also determined the sequence of its large central
      tandem repeat array. The 5'-region reveals high degree of sequence similarity
      with MUC2 and MUC5B and codes for 1336 amino acids organized into a signal
      peptide, four pro-von Willebrand factor-like D domains (D1, D2, D' and D3) and a
      short domain which connects to the central repetitive region. In the central
      region, 17 major domains have been identified. Nine code for cysteine-rich
      domains (Cys-domains 1-9) and exhibit high sequence similarity to the cysteine
      rich domains described in the central region of MUC2 and MUC5B. Cys-domains 1-5
      are interspersed by domains enriched with serine, threonine, and proline
      residues. Cys-domains 1-9 are interspersed by four domains (TR1-TR4) composed of
      various numbers of MUC5AC-type repeats. Southern-blot analyses reveal allelic
      variations both in length and nucleotide sequence. The length polymorphism which
      is due to variable numbers of tandem repeats is located in TR1 and TR4, whereas a
      mutation polymorphism detected with TaqI is located in Cys-domain 6. In this
      study, the organization of MUC5AC has been entirely elucidated showing extensive
      similarity to the other chromosome 11p15 MUC genes, particularly MUC5B, and
      providing additional arguments for common evolution from a single ancestral gene.

PMID- 11535138
TI  - Lipolytic activity of ricin from Ricinus sanguineus and Ricinus communis on
      neutral lipids.
AB  - The present study was carried out with a view of determining ricin lipolytic
      activity on neutral lipids in emulsion and in a membrane-like model. Using 2,3
      dimercapto-1-propanol tributyrate (BAL-TC(4)) as substrate, the lipolytic
      activity of ricin was found to be proportional to ricin and substrate
      concentrations, with an apparent K(m) (K(m,app)) of 2.4 mM, a k(cat) of 200 min(
      1) and a specific activity of 1.0 unit/mg of protein. This work was extended to p
      nitrophenyl (pNP) fatty acid esters containing two to twelve carbon atoms.
      Maximum lipolytic activity was registered on pNP decanoate (pNPC(10)), with a
      K(m,app) of 3.5 mM, a k(cat) of 173 min(-1) and a specific activity of 3.5
      units/mg of protein. Ricin lipolytic activity is pH and galactose dependent, with
      a maximum at pH 7.0 in the presence of 0.2 M galactose. Using the monolayer
      technique with dicaprin as substrate, ricin showed a lipolytic activity
      proportional to the ricin concentration at 20 mN/m, which is dependent on the
      surface pressure of the lipid monolayer and is detectable up to 30 mN/m, a
      surface pressure that is of the same order of magnitude as that of natural cell
      membranes. The methods based on pNPC(10) and BAL-TC(4) hydrolysis are simple and
      reproducible; thus they can be used for routine studies of ricin lipolytic
      activity. Ricin from Ricinus communis and R. sanguineus were treated with diethyl
      p-nitrophenylphosphate, an irreversible serine esterase inhibitor, and their
      lipolytic activities on BAL-TC(4) and pNPC(10), and cytotoxic activity, were
      concurrently recorded. A reduction in lipolytic activity was accompanied by a
      decrease in cytotoxicity on Caco2 cells. These data support the idea that the
      lipolytic activity associated with ricin is relevant to a lipase whose activity
      is pH and galactose dependent, sensitive to diethyl p-nitrophenylphosphate, and
      that a lipolytic step may be involved in the process of cell poisoning by ricin.
      Both colorimetric tests used in this study are sensitive enough to be helpful in
      the detection of possible lipolytic activities associated with other cytotoxins
      or lectins.

PMID- 11535140
TI  - Audiological findings in pregnancy.
AB  - This investigation was carried out in the Audiology and Speech Pathology Section
      of the Department of Otorhinolaryngology of Hacettepe University. The pregnant
      group comprised of 20 women followed by the Department of Gynaecology and
      Obstetrics of the same university; 18 non-pregnant women comprised the control
      group. The aim of this investigation was to study the relationship between
      hormonal changes in pregnancy and cochlear functions. All subjects underwent ENT
      examination, audiologic and acoustic immitance measurements and auditory brain
      stem response (ABR) tests. Results from each trimester and post-partum period of
      the pregnant group were compared. These results demonstrated that there was a
      decrease in hearing levels for 125 Hz, beginning in the first trimester and
      increasing in the second and third trimesters. Hearing returned to normal in the
      post-partum period. Similar findings were also obtained for 250 and 500 Hz;
      however, frequencies higher than 500 Hz demonstrated no significant correlation.
      Uncomfortable loudness was statistically significant between the third trimester
      and post-partum period. ABR tests did not reveal any differences. In conclusion,
      there is a low-frequency hearing loss and tolerance problem in pregnancy
      mimicking cochlear pathology. However, this hearing loss did not reach pathologic
      levels in any case and returned to normal in the post-partum period.

PMID- 11535139
TI  - Phosphorylation of the leucocyte NADPH oxidase subunit p47(phox) by casein kinase
      2: conformation-dependent phosphorylation and modulation of oxidase activity.
AB  - The leucocyte NADPH oxidase of neutrophils is a membrane-bound enzyme that
      catalyses the reduction of oxygen to O(-)(2) at the expense of NADPH. The enzyme
      is dormant in resting neutrophils but becomes active when the cells are exposed
      to the appropriate stimuli. During oxidase activation, the highly basic cytosolic
      oxidase component p47(phox) becomes phosphorylated on several serines and
      migrates to the plasma membrane. Protein kinase CK2 is an essential
      serine/threonine kinase present in all eukaryotic organisms. The leucocyte NADPH
      oxidase subunit p47(phox) has several putative CK2 phosphorylation sites. In the
      present study, we report that CK2 is able to catalyse the phosphorylation of
      p47(phox) in vitro. Phosphoamino acid analysis of phosphorylated p47(phox) by CK2
      indicated that the phosphorylation occurs on serine residues. CNBr mapping and
      phosphorylation of peptides containing the putative site of CK2 indicated that
      the main phosphorylated residues are Ser-208 and Ser-283 in the Src homology 3
      (SH3) domains, and Ser-348 in the C-terminal domain of p47(phox). Dependence of
      phosphorylation on the conformation of p47(phox) is supported by the finding that
      p47(phox) undergoes better phosphorylation by CK2 in the presence of arachidonic
      acid, a known activator of NADPH oxidase which induces conformational changes in
      p47(phox). In addition, 5,6-dichloro-1-beta-o-ribofuranosyl benzimidazole, a CK2
      inhibitor, potentiates formyl-Met-Leu-Phe-induced NADPH oxidase activity in DMSO
      differentiated HL-60 cells. Taken together, we propose that CK2 is the p47(phox)
      kinase, and that phosphorylation of p47(phox) by CK2 regulates the deactivation
      of NADPH oxidase.

PMID- 11535141
TI  - Reversible ototoxic effect of azithromycin and clarithromycin on transiently
      evoked otoacoustic emissions in guinea pigs.
AB  - The possible cochlear toxicity of systemically applied macrolides--erythromycin
      (ER), azithromycin (AZ) and clarithromycin(CL)--was investigated in guinea pigs
      by measuring transiently evoked otoacoustic emissions (TEOAEs). A single dose of
      125 mg/kg intravenous (i.v.) ER caused no change in TEOAEs in guinea pigs
      (p>0.05), whereas AZ (45 mg/kg orally) and CL (75 mg/kg i.v.) reversibly reduced
      the emission response (p<0.05). The reversible reduction of TEOAE responses due
      to AZ and CL, which is in accordance with the clinical picture of AZ and CL
      ototoxicity, could likely be attributable to the transient dysfunction of outer
      hair cells. The present study reveals that at least one ototoxic effect of AZ and
      CL is on the inner ear. The results may also encourage planning clinical
      researches on TEOAE monitoring in patients receiving high doses of AZ or CL.

PMID- 11535142
TI  - Prevalence of nasal mucosal contact points in patients with facial pain compared
      with patients without facial pain.
AB  - A cohort of 973 consecutive attendants at a rhinology clinic was studied
      prospectively and divided into patients without facial pain (n = 566, 58 per
      cent) and patients with facial pain (n = 407, 42 per cent). The prevalence of
      nasal mucosal contact points was the same in both groups, being four per cent in
      patients with nasal contact points without facial pain and four per cent in
      patients with facial pain. A contact point is defined as when contact remains
      after topical decongestion. Of the 18 patients with facial pain, nine had a spur
      contacting the lateral nasal wall and nine had a middle turbinate contacting the
      septum. These 18 patients were followed up for a mean of two years and two
      months. In the light of their treatment and response the following diagnoses were
      made: five had tension-type headache, six had midfacial segment pain, one had
      migraine, two had cluster headache and four had purulent nasal disease. Of the
      four with unilateral symptoms, two had a contact point on the contralateral side.
      Eleven of these 18 patients responded to medical treatment for tension-type
      headache or midfacial segment pain, migraine and cluster headache, three patients
      were better after surgery for coexisting purulent nasal disease and one patient
      had a spur removed surgically and remained better at 2 years follow-up, whereas
      three patients were no better after the same procedure. The results demonstrate
      that the prevalence of nasal contact points in patients with facial pain is the
      same as in those within pain. Surgery undertaken to remove mucosal contact points
      for facial pain is usually unnecessary as the aetiology of this facial pain
      appears to be a more central processes.

PMID- 11535143
TI  - Most patients overdose on topical nasal corticosteroid drops: an accurate
      delivery device is required.
AB  - Otolaryngologists and general practitioners commonly prescribed intranasal
      corticosteroid drops for rhinitis. Compliance in real patients has not previously
      been studied, but is generally believed to be poor. Recent concerns over systemic
      adverse effects of topical corticosteroids have highlighted the risks of
      overdosing. Fifty patients, who were prescribed betamethasone, were prospectively
      studied for accuracy of compliance using a weighed dose study. Patients
      consistently administered inaccurate quantities of nasal corticosteroid drops,
      with a marked tendency to overdose up to four times the recommended daily dose
      (RDD) in some cases. The mean dose administered was 200 per cent of the RDD. Of
      the 50 patients, only seven (14 per cent) administered the correct dose. The
      introduction of metered-dose delivery systems should be considered to reduce the
      risk of inadvertent overdosing.

PMID- 11535145
TI  - The importance of dedifferentiation in recurrent acinic cell carcinoma.
AB  - The biological activity of acinic cell carcinoma is uncertain. Histological
      dedifferentiation is one possible reason for recurrent disease, and this study
      was undertaken to assess its importance in acinic cell carcinoma. The initial and
      recurrent specimens from five patients with acinic cell carcinoma were assessed
      histologically and using flow cytometry, AgNOR estimation and morphometric
      analysis for evidence of dedifferentiation. No objective evidence of a change in
      biological aggressiveness in recurrent acinic cell carcinoma was identified. In
      this limited series of a rare salivary gland tumour, it would appear that factors
      other than dedifferentiation, such as close/involved margins, histological type
      and stage have a more meaningful effect on the likelihood of recurrence and
      prognosis.

PMID- 11535144
TI  - Increasing diagnostic yield in allergic fungal sinusitis.
AB  - Diagnosis of allergic fungal sinusitis (AFS) in patients who present with
      rhinosinusitis and polyposis is based upon certain clinical, histopathological
      and mycological histopathological criteria are the demonstration of fungal hyphae
      in allergic mucin and absence of tissue invasion in the excised polyps. Previous
      reports have indicated difficulty in demonstrating fungal hyphae on histological
      examination in up to 75 per cent of cases. Analysis of a series of 25 patients
      with AFS, suggested methods to ensure demonstration of fungal hyphae and thus
      increase diagnostic yield in cases with suspected AFS. criteria. Specific
      diagnostic

PMID- 11535146
TI  - Reducing waiting times for sleep apnoea hypopnoea syndrome and snoring using a
      questionnaire and home oximetry: results of a second audit cycle.
AB  - As a result of a previous audit on the management of sleep apnoea hypopnoea
      syndrome (SAHS) which showed long waiting times that were primarily due to
      unnecessary interspecialty referrals, a change in practice was adopted. All
      referrals are now sent a questionnaire about symptoms suggestive of SAHS, the
      Epworth Sleepiness Scale score and their body mass index (BMI) which when
      returned are categorized into having a high, intermediate or low risk of SAHS.
      Those patients with a high probability have home overnight oximetry and those
      with intermediate probability have video oximetry. Those with a low probability
      are referred directly to ENT. We audited the first 100 patients referred. All
      were General Practitioner referrals to either ENT or respiratory medicine. Only
      two patients had a low probability score and were seen directly in ENT. Following
      sleep study analysis, 10 patients were referred directly to ENT with no
      respiratory medicine follow-up and nine were discharged back to the General
      Practitioner with no apnoea or snoring. Eighty-one patients were followed up by
      respiratory medicine. Of these, 49 received a trial of nasal continuous positive
      airway pressure (nCPAP) and six were referred to ENT. Therefore the majority
      justified an investigation to exclude SAHS in the first instance and an
      unnecessary initial ENT appointment was avoided. We have reduced the average
      waiting times to sleep study by approximately 90 days and to nCPAP trial by 32
      days, mostly due to decreased delays in interspeciality referrrals. We have also
      demonstrated a greater than 50 per cent reduction in ENT clinic visits, a small
      increase in the number of sleep studies but no increase in respiratory clinic
      workload.

PMID- 11535147
TI  - Cost-effective diagnostic nasal endoscopy with a modified otoscope.
AB  - We present 'Mishra's rhinoscope', a novel, cost-effective technique of zero
      degree rigid nasoendoscopy with a modified otoscope, the results of which are
      comparable with the fibreoptic sinoscope. This is particularly suited for the
      developing world where financial constraints restrict the diagnosis of an occult
      nasal pathology.

PMID- 11535148
TI  - Application of cocaine to the nasal mucosa: a novel method.
AB  - Topical vasoconstriction using four to 10 per cent cocaine is widely used for
      nasal surgery. A number of techniques are being used with equally satisfactory
      results. Here we describe a novel method of topical application of cocaine for
      nasal surgery. The method is simple, cheap and effective.

PMID- 11535149
TI  - Recurrent infestation of the mastoid cavity with Caloglyphus berlesei: an
      occupational hazard.
AB  - Mite infestation of the ear is an unusual clinical problem that is easily cured
      with simple measures and recurrent infestation has not been reported till date.
      We present here a patient who developed recurrent infestation of otherwise
      healthy mastoid cavities with the storage mite Caloglyphus berlesei, secondary to
      occupational exposure. This kind of recurrent mite infestation of the ear has not
      been described before.

PMID- 11535150
TI  - Ossifying fibroma of the temporal bone.
AB  - A rare case of ossifying fibroma of the temporal bone is presented. Fibro-osseous
      lesions are benign neoplasms but may show an aggressive behaviour when invading
      important anatomical structures. The lack of experience in the treatment of those
      tumours is reflected in the small relative literature. The purpose of this paper
      is to contribute to the few cases already reported.

PMID- 11535151
TI  - Open septorhinoplasty approach for the excision of a dermoid cyst and sinus with
      primary dorsal reconstruction.
AB  - Adult nasal dermoid cysts and sinuses are rare. Here we describe the surgical
      management of a 37-year-old patient with a longstanding nasal dermoid cyst and
      discharging sinus. A combination of an open rhinoplasty approach with a small
      dorsal incision was used to excise the lesion followed by primary reconstruction
      with septal cartilage.

PMID- 11535152
TI  - Tubercular laryngeal abscess.
AB  - Tuberculosis, with its varied presentations and numerous complications, is a
      relatively common disease in developing countries like India. Amongst its many
      presentations, pulmonary tuberculosis is the commonest. A tubercular laryngeal
      abscess is an extremely rare entity. We report a 37-year-old male, diagnosed with
      a tubercular laryngeal abscess which was successfully treated under local
      anaesthesia by incision and drainage and in whom a tracheostomy could be avoided.

PMID- 11535153
TI  - Bilateral aneurysms of the extracranial internal carotid artery presenting as
      vocal fold palsy.
AB  - Bilateral extracranial internal carotid aneurysms are very rare, though well
      documented. We report a case of bilateral extracranial internal carotid aneurysms
      presenting with vocal fold paralysis, which we believe to be the first.

PMID- 11535154
TI  - Idiopathic lymphoepithelial cyst of the parapharynx masquerading as peritonsillar
      abscess.
AB  - We present a case of a 38-year-old man who was referred to us with a right-sided
      quinsy. However he was found to have a large lympho-epithelial cyst in his right
      parapharynx mimicking the signs of a quinsy to the unsuspecting eye. We describe
      this case to illustrate an unusual cause of a swelling of the lateral pharyngeal
      wall.

PMID- 11535155
TI  - Delayed oesophageal perforation following endoscopic stapling of a pharyngeal
      pouch.
AB  - Endoscopic stapling of pharyngeal pouches is gaining popularity and is said to be
      a quick procedure with minimal morbidity and mortality. So far, there have been
      few reported cases of any severe complications following this procedure. However,
      complications as with other treatment modalities can occur. A case of
      mediastinitis due to delayed oesophageal perforation following the stapling
      procedure is presented.

PMID- 11535156
TI  - Evaluation of persistent torticollis following adenoidectomy.
AB  - Post-operative neck complaints are not an uncommon finding following
      adenotonsillectomy. However, non-traumatic subluxation of the atlantoaxial joint
      (Grisel's syndrome) should be considered in cases of persistent neck pain and
      stiffness. An early diagnosis and adequate treatment of this rare condition is
      mandatory to prevent potentially serious complications. We describe three cases
      with persistent torticollis in the post-operative period, discuss the
      pathogenesis and evaluate the clinical management of these patients.

PMID- 11535157
TI  - Primary cutaneous adenoid cystic carcinoma with regional lymph node metastasis.
AB  - Primary cutaneous adenoid cystic carcinoma (PCACC) is a particularly rare variant
      of sweat gland carcinoma with characteristics of indolent and progressive course
      and high incidence of perineural invasion and local recurrence. However, regional
      lymph node metastasis in PCACC is exceedingly rare and its prognostic implication
      is unknown. Only two previous cases of recurrent scalp PCACC were reported to be
      associated with cervical lymph node metastases at 42 months and 20 years,
      respectively, after the initial treatment. We present a case of PCACC occurring
      in the left parotid region with regional neck lymph node metastasis in a 64-year
      old man. Because the occurrence of lymph node metastasis seems to be associated
      with recurrent PCACC, we suggest that neck dissection may be included in the
      treatment for recurrent PCACC patients.

PMID- 11535158
TI  - Sinusitis in the hypoplastic maxillary antrum: the crucial role of radiology in
      diagnosis and management.
AB  - Maxillary sinus hypoplasia (MSH) is occasionally encountered in
      otorhinolaryngological practice. The hypoplastic sinus is liable to mucus
      retention, and cases of MSH usually present as a persistent maxillary sinusitis.
      Endoscopic surgery has been recommended as an effective treatment for the sinus
      infection. However, MSH is associated with anomalies of the lateral nasal wall
      which, if not recognized pre-operatively, can lead to inadvertent surgical damage
      to the orbit. Although some of these abnormalities can be evident endoscopically,
      the role of imaging in diagnosis and identification of important surgical
      landmarks is paramount. A posteriorly placed middle meatal antrostomy is
      recommended as the surgical treatment of choice.

PMID- 11535159
TI  - Palatal presentation of scleroma.
AB  - A case with palatal presentation of scleroma is presented due to its rarity and
      unusual manifestations. The patient presented with only palatal symptoms. Nasal
      endoscopy revealed signs of all three stages of scleroma: catarrhal,
      granulomatous and sclerotic stages. Histopathology was vital in the diagnosis.
      The patient was treated by medical therapy, and palatal symptoms were relieved by
      uvulopalatopharyngoplasty.

PMID- 11535160
TI  - Chondroid metaplasia in a fibroepithelial polyp of the tongue.
AB  - This report describes the development of chondroid metaplasia within a
      fibroepithelial polyp situated on the tongue. Although fibroepithelial polyps in
      this location are not unusual, chondroid metaplasia in such a lesion in this
      position has not, as far as the authors are aware, been described previously. The
      aetiology and the pathogenesis of the lesion are discussed.

PMID- 11535161
TI  - Metachronous bilateral submandibular gland metastases from carcinoma of the
      breast.
AB  - Metastases to the salivary glands from distant neoplasms are unusual, with most
      reported cases involving the parotid gland. Metastatic deposits in the
      submandibular gland are extremely rare with bilateral involvement not previously
      reported. We present the case of a patient with advanced breast carcinoma who has
      had metachronous involvement of both submandibular glands and review the
      literature on this subject.

PMID- 11535163
TI  - A warning to users of disposable tonsillectomy instruments.

PMID- 11535164
TI  - How to optimize in vivo gene transfer to cardiac myocytes: mechanical or
      pharmacological procedures?
AB  - An efficient gene delivery system is a prerequisite for myocardial gene therapy.
      Among the various procedures studied so far, catheter-based percutaneous gene
      delivery to the myocardium through the coronary vessels seems the most relevant
      to routine clinical practice; however, the optimal conditions remain to be
      determined. We selectively infused adenoviral vectors encoding luciferase (1 x
      10(9) PFU) or beta-galactosidase (1 x 10(10) PFU) into coronary arteries of adult
      rabbits in various experimental conditions. Coronary artery occlusion for 30 sec,
      during and after adenovirus delivery, was required to observe luciferase activity
      in the target area of the circumflex artery (4.0 +/- 1.0 x 10(5) vs. 1.1 +/- 0.2
      x 10(4) RLU/mg with and without coronary occlusion, respectively, p < 0.01, and
      1.0 +/- 0.1 x 10(3) RLU/mg using nonselective infusion). When adenoviruses were
      delivered using high-pressure infusion (82 +/- 12 vs. 415 +/- 25 mmHg before and
      during infusion, respectively, p < 0.01), luciferase activity increased to 8.5 +/
      2.5 x 10(5) RLU/mg (p < 0.05 vs coronary occlusion alone). Coronary venous sinus
      occlusion with saline buffer retroinfusion starting before and during anterograde
      adenovirus delivery resulted in a further 4.7-fold increase in luciferase
      activity (4.4 +/- 0.8 x 10(6) RLU/mg, p < 0.01) with 5-25% blue-stained myocytes
      in the target area, compared with 0-5% with the other procedures. Histamine or
      VEGF-A(165) pretreatment, used to increase vascular permeability, slightly
      increased gene transfer efficiency (8.5 +/- 2.0 x 10(5) and 9.0 +/- 2.5 x 10(5)
      RLU/mg respectively, p < 0.05 vs. coronary occlusion alone). We conclude that
      catheter-mediated adenoviral gene transfer to cardiac myocytes through coronary
      vessels can be a very efficient procedure for myocardial gene therapy,
      particularly when the vector residence time and perfusion pressure in the vessels
      are increased.

PMID- 11535165
TI  - Complexation of retrovirus with cationic and anionic polymers increases the
      efficiency of gene transfer.
AB  - Previously, we have demonstrated that chondroitin sulfate proteoglycans and
      glycosaminoglycans inhibit retrovirus transduction. While studying the mechanism
      of inhibition, we found that the combined addition of equal-weight concentrations
      (80 microg/ml) of Polybrene and chondroitin sulfate C to retrovirus stocks
      resulted in the formation of a high-molecular-weight retrovirus-polymer complex
      that could be pelleted by low-speed centrifugation. The pelleted complex
      contained more than 80% of the virus particles, but less than 0.3% of the
      proteins that were originally present in the virus stock. Surprisingly, the virus
      in the complex remained active and could be used to transduce cells. The titer of
      the pelleted virus, when resuspended in cell culture medium to the starting
      volume, was three-fold greater than the original virus stock. The selectivity
      (CFU/mg protein) of the process with respect to virus activity was more than 1000
      fold. When the pelleted virus-polymer complex was resuspended in one-eighth of
      the original volume and used to transduce NIH 3T3 murine fibroblasts and primary
      human fibroblasts, gene transfer was increased 10- to 20-fold over the original
      unconcentrated retrovirus stock. The implications of our findings for the
      production, processing, and use of retrovirus stocks for human gene therapy
      protocols are discussed.

PMID- 11535166
TI  - Gene combination raises broad human immunodeficiency virus-specific cytotoxicity.
AB  - DNA plasmid immunization has the important advantage over traditional vaccines of
      making it possible to combine selected genes into one vaccine. The efficacy of a
      combination of DNA plasmids encoding the nef, rev, and tat HIV-1 regulatory genes
      in inducing cellular immune responses was analyzed in asymptomatic HIV-1-infected
      patients. Patients initially selected for having low or no detectable immune
      responses to Nef, Rev, or Tat antigens developed MHC class I-restricted cytolytic
      activities as well as enhanced bystander effects. The induction of memory cells
      against target cells infected with the whole HIV-1 genome was analyzed by using a
      pseudovirus HIV-1/murine leukemia virus (MuLV), and target cells infected with
      vaccinia virus carrying the respective gene. The most remarkable change observed
      after immunization with the gene combination was an increase in cytotoxic T
      lymphocyte (CTL) precursors to target cells infected with the whole HIV-1 genome.
      Infection by the pseudotype HIV-1/MuLV virus should result in a multitude of HIV
      1 peptides presented on the target cell surface, representative of the in vivo
      situation. An in vitro assessment of the expression of the single and combined
      gene products showed that this was consistent with the induction of CTL responses
      in vivo. No clinical advantage or adverse effects were noted. Therapeutic effects
      of such immunization may become measurable by structured therapy interruption.

PMID- 11535167
TI  - Adenovirus gene transfer vectors inhibit growth of lymphatic tumor metastases
      independent of a therapeutic transgene.
AB  - Adenovirus (Ad) gene transfer vectors traffic to regional lymph nodes (RLNs)
      after footpad injections in mice, resulting in localized production of interferon
      gamma (IFN-gamma). With this background, we evaluated the hypothesis that Ad
      vector administration may inhibit RLN tumor metastasis independent of the
      transgene in the expression cassette. Tumors of MM48, a cell line with a
      propensity toward lymphogenous metastasis, were established in the footpads of
      syngeneic C3H mice, and E1(-)E3(-) Ad vectors encoding no transgene (AdNull) or
      encoding an irrelevant transgene (AdCD; Escherichia coli cytosine deaminase with
      no 5-fluorocytosine administration) were administered (10(10) particles) in a
      peritumoral location. Both vectors suppressed the growth of tumor in the regional
      (popliteal) lymph node. This effect was localized to the regional, but not
      distant, lymph nodes (p < 0.05). Heat inactivation of the vector or decreasing
      the dose of the vector to 10(9) particles did not suppress RLN growth of the
      tumor when compared with 10(10) particles of active AdNull (p < 0.05 and p <
      0.01, respectively). The ability of an E1(-)E4(-) vector expressing beta
      galactosidase (AdRSVbetagal.11) to suppress RLN tumor growth showed that the E4
      region of the Ad vector was not responsible for the effect. Blocking either IFN
      gamma or natural killer (NK) cells with systemic antibody treatment in
      immunocompetent mice allowed rapid growth of RLN metastases despite Ad vector
      administration, and Ad vector injection into the footpads of tumor-free mice
      induced the accumulation of NK cells in the RLN. These data demonstrate that, in
      a metastatic murine tumor model, a low dose (10(10) particles) of replication
      deficient Ad vectors inhibits RLN metastases independent of a therapeutic
      transgene, an effect that is mediated, at least in part, by IFN-gamma and NK
      cells.

PMID- 11535168
TI  - Adenovirus-mediated factor VIII gene expression results in attenuated anti-factor
      VIII-specific immunity in hemophilia A mice compared with factor VIII protein
      infusion.
AB  - Hemophilia A patients are typically treated by factor VIII (FVIII) protein
      replacement, an expensive therapy that induces FVIII-specific inhibitors in
      approximately 30% of patients with severe hemophilia. FVIII gene therapy has the
      potential to improve the current treatment protocols. In this report, we used a
      hemophilia A mouse model to compare the humoral and cellular immune responses
      between an E1/E2a/E3-deficient adenovirus expressing human FVIII directed by a
      liver-specific albumin promoter and purified recombinant FVIII protein infusion.
      Adenovirus-mediated FVIII expression did not elicit detectable CD4+ or CD8+ T
      cell responses and induced a weak antibody immune response to FVIII. In contrast,
      FVIII protein administration resulted in a potent anti-FVIII antibody response
      and moderate CD4+ T cell response. Furthermore, hemophiliac mice preimmunized
      with FVIII protein infusion to induce anti-FVIII immunity, and subsequently
      treated by adenovirus-mediated FVIII gene therapy, expressed therapeutic levels
      of FVIII despite the presence of low levels of anti-FVIII antibodies. No FVIII
      was detected in the plasma of mice with intermediate or high antibody levels,
      although anti-FVIII antibody levels in some vector-treated animals declined. The
      data support the hypothesis that liver-specific gene therapy-mediated expression
      of FVIII may be less immunogenic than traditional protein replacement therapy.

PMID- 11535169
TI  - In vivo persistence of retrovirally transduced murine long-term repopulating
      cells is not limited by expression of foreign gene products in the fully or
      minimally myeloablated setting.
AB  - Many nonmalignant hematologic disorders could potentially be treated by genetic
      correction of as few as 5-10% of target lineage cells. However, immune system
      clearance of cells expressing gene products perceived as foreign could be
      limiting. There is evidence that tolerance to foreign proteins can result when
      myeloablative conditioning is used, but this limits the overall applicability of
      such techniques. Therefore, we sought to evaluate the engraftment of
      hematopoietic stem cells carrying a foreign transgene after low-dose irradiation
      by comparing in vivo survival of murine long-term repopulating cells (LTRC)
      transduced with either a retroviral vector expressing the bacterial neomycin
      phosphotransferase gene (neo) or a vector containing neo gene sequences but
      modified to prevent protein expression (nonexpression). First, marrow cells from
      congenic donors were transduced with either vector and transplanted into
      recipients treated with standard dose irradiation of 800 rads. High-level
      engraftment and gene marking resulted, without differences in the marking levels
      or pattern of persistence of the cells between cells transduced with either
      vector. Low-dose irradiation at 100 rads was tested using higher cell doses.
      Marking levels as high as 10% overall were obtained, again with no differences
      between mice receiving cells transduced with the neo versus the nonexpression
      vectors. To investigate a potentially more immunogenic protein, marrow cells were
      transduced with a vector containing the green fluorescent protein (GFP) gene, and
      their persistence was studied in recipient mice receiving 100 rads. Stable GFP
      expression in 5-10% of circulating cells was observed long term. We conclude that
      even with very low dose conditioning, engraftment by genetically modified LTRC
      cells at clinically significant levels can be achieved without evidence for
      clearance of cells known to be expressing immunogenic proteins.

PMID- 11535170
TI  - A novel parasite-derived suicide gene for cancer gene therapy with specificity
      for lung cancer cells.
AB  - The enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT) expressed by
      the parasite Trypanosoma brucei (Tb) can convert allopurinol, a purine analogue,
      to corresponding nucleotides with greater efficiency than its human homologue. We
      have developed a retroviral system that expresses the parasitic enzyme and tested
      its capacity to activate the prodrug allopurinol to a cytotoxic metabolite.
      Cytotoxicity assays demonstrated that five non-small cell lung carcinoma cell
      lines transduced with the construct were sensitized to the prodrug by 2.1- to 7.6
      fold compared with control values. This selectivity was not observed in seven
      other cell lines also expressing the construct, such as breast carcinoma. Assays
      indicated that enhanced cytotoxicity to allopurinol correlated with induction of
      apoptosis in lung cancer cells. The selectivity of this suicide gene was not
      explained either by the TbHGPRT expression or by the allopurinol accumulation.
      Our study shows that this novel system may represent a therapeutic tool for gene
      prodrug targeting of lung cancer, considering the fact that allopurinol is well
      tolerated in humans.

PMID- 11535173
TI  - On combinatorial DNA word design.
AB  - We consider the problem of designing DNA codes, namely sets of equi-length words
      over the alphabet [A, C, G, T] that satisfy certain combinatorial constraints.
      This problem is motivated by the task of reliably storing and retrieving
      information in synthetic DNA strands for use in DNA computing or as molecular bar
      codes in chemical libraries. The primary constraints that we consider, defined
      with respect to a parameter d, are as follows: for every pair of words w, x in a
      code, there are at least d mismatches between w and x if w not equal x and also
      between the reverse of w and the Watson-Crick complement of x. Extending
      classical results from coding theory, we present several upper and lower bounds
      on the maximum size of such DNA codes and give methods for constructing such
      codes. An additional constraint that is relevant to the design of DNA codes is
      that the free energies and enthalpies of the code words, and thus the melting
      temperatures, be similar. We describe dynamic programming algorithms that can (a)
      calculate the total number of words of length n whose free energy value, as
      approximated by a formula of Breslauer et al. (1986) falls in a given range, and
      (b) output a random such word. These algorithms are intended for use in heuristic
      algorithms for constructing DNA codes.

PMID- 11535174
TI  - Mathematical modeling for functional divergence after gene duplication.
AB  - In this paper, I present a statistical framework for modeling the functional
      divergence after gene duplication. A rate-component model to describe the rate
      covariation among homologous genes of a gene family is implemented when a
      phylogenetic tree is known. The Markov chain model is rigorous but may require a
      huge amount of computational time when the number of sequences is large. On the
      other hand, the Poisson-based model is mathematically analytical so that
      computation is very fast even for a large dataset. Moreover, under the posterior
      framework, we have developed a site-specific profile for predicting important
      amino acid residues responsible for these functional differences between member
      genes of a gene family. Our study may have great potential for functional
      genomics because it is cost-effective, and these predictions can be further
      tested by biological experimentation.

PMID- 11535175
TI  - Fast approximate motif statistics.
AB  - We present in this article a fast approximate method for computing the statistics
      of a number of non-self-overlapping matches of motifs in a random text in the
      nonuniform Bernoulli model. This method is well suited for protein motifs where
      the probability of self-overlap of motifs is small. For 96% of the PROSITE
      motifs, the expectations of occurrences of the motifs in a 7-million-amino-acids
      random database are computed by the approximate method with less than 1% error
      when compared with the exact method. Processing of the whole PROSITE takes about
      30 seconds with the approximate method. We apply this new method to a comparison
      of the C. elegans and S. cerevisiae proteomes.

PMID- 11535176
TI  - Statistical significance of probabilistic sequence alignment and related local
      hidden Markov models.
AB  - The score statistics of probabilistic gapped local alignment of random sequences
      is investigated both analytically and numerically. The full probabilistic
      algorithm (e.g., the "local" version of maximum-likelihood or hidden Markov model
      method) is found to have anomalous statistics. A modified "semi-probabilistic"
      alignment consisting of a hybrid of Smith-Waterman and probabilistic alignment is
      then proposed and studied in detail. It is predicted that the score statistics of
      the hybrid algorithm is of the Gumbel universal form, with the key Gumbel
      parameter lambda taking on a fixed asymptotic value for a wide variety of scoring
      systems and parameters. A simple recipe for the computation of the "relative
      entropy," and from it the finite size correction to lambda, is also given. These
      predictions compare well with direct numerical simulations for sequences of
      lengths between 100 and 1,000 examined using various PAM substitution scores and
      affine gap functions. The sensitivity of the hybrid method in the detection of
      sequence homology is also studied using correlated sequences generated from toy
      mutation models. It is found to be comparable to that of the Smith-Waterman
      alignment and significantly better than the Viterbi version of the probabilistic
      alignment.

PMID- 11535177
TI  - Tsukuba BB: a branch and bound algorithm for local multiple alignment of DNA and
      protein sequences.
AB  - In this paper we present a branch and bound algorithm for local gapless multiple
      sequence alignment (motif alignment) and its implementation. The algorithm uses
      both score-based bounding and a novel bounding technique based on the
      "consistency" of the alignment. A sequence order independent search tree is used
      in conjunction with a technique for avoiding redundant calculations inherent in
      the structure of the tree. This is the first program to exploit the fact that the
      motif alignment problem is easier for short motifs. Indeed, for a short fixed
      motif width, the running time of the algorithm is asymptotically linear in the
      size of the input. We tested the performance of the program on a dataset of 300
      E. coli promoter sequences and a dataset of 85 lipocalin protein sequences. For a
      motif width of 4, the optimal alignment of the entire set of sequences can be
      found. For the more natural motif width of 6, the program can align 21 sequences
      of length 100, more than twice the number of sequences which can be aligned by
      the best previous exact algorithm. The algorithm can relax the constraint of
      requiring each sequence to be aligned, and align 105 of the 300 promoter
      sequences with a motif width of 6. For the lipocalin dataset, we introduce a
      technique for reducing the effective alphabet size with a minimal loss of useful
      information. With this technique, we show that the program can find meaningful
      motifs in a reasonable amount of time by optimizing the score over three motif
      positions.

PMID- 11535178
TI  - Inference of haplotypes from samples of diploid populations: complexity and
      algorithms.
AB  - The next phase of human genomics will involve large-scale screens of populations
      for significant DNA polymorphisms, notably single nucleotide polymorphisms
      (SNPs). Dense human SNP maps are currently under construction. However, the
      utility of those maps and screens will be limited by the fact that humans are
      diploid and it is presently difficult to get separate data on the two "copies."
      Hence, genotype (blended) SNP data will be collected, and the desired haplotype
      (partitioned) data must then be (partially) inferred. A particular
      nondeterministic inference algorithm was proposed and studied by Clark (1990) and
      extensively used by Clark et al. (1998). In this paper, we more closely examine
      that inference method and the question of whether we can obtain an efficient,
      deterministic variant to optimize the obtained inferences. We show that the
      problem is NP-hard and, in fact, Max-SNP complete; that the reduction creates
      problem instances conforming to a severe restriction believed to hold in real
      data (Clark, 1990); and that even if we first use a natural exponential-time
      operation, the remaining optimization problem is NP-hard. However, we also
      develop, implement, and test an approach based on that operation and (integer)
      linear programming. The approach works quickly and correctly on simulated data.

PMID- 11535179
TI  - A dynamic programming approach to de novo peptide sequencing via tandem mass
      spectrometry.
AB  - Tandem mass spectrometry fragments a large number of molecules of the same
      peptide sequence into charged molecules of prefix and suffix peptide subsequences
      and then measures mass/charge ratios of these ions. The de novo peptide
      sequencing problem is to reconstruct the peptide sequence from a given tandem
      mass spectral data of k ions. By implicitly transforming the spectral data into
      an NC-spectrum graph G (V, E) where /V/ = 2k + 2, we can solve this problem in
      O(/V//E/) time and O(/V/2) space using dynamic programming. For an ideal noise
      free spectrum with only b- and y-ions, we improve the algorithm to O(/V/ + /E/)
      time and O(/V/) space. Our approach can be further used to discover a modified
      amino acid in O(/V//E/) time. The algorithms have been implemented and tested on
      experimental data.

PMID- 11535180
TI  - From Jabberwocky to genome: Lewis Carroll and computational biology.
AB  - In addition to his literary output, Lewis Carroll created a vast range of games
      and puzzles that depend upon wordplay of various kinds, especially the
      manipulation of alphabetic symbols in diverse contexts. Such wordplay reveals a
      turn of mind well suited to methodologies used in modern computational biology.

PMID- 11535182
TI  - [Advances in the diagnosis of arterial disease by magnetic resonance imaging].
AB  - Magnetic resonance imaging is proving to be a very useful non-invasive imaging
      technique in the study of the long-term evolution of atheroma lesions. Not only
      is it applicable for the diagnosis of atherosclerotic disease but also for the
      characterization of the cellular mechanisms implied in the development of
      vascular damage. The four main lesions found in atherosclerosis the onset of the
      lesion with the appearance of remodeling, the development of vulnerable plaque,
      thrombus formation and the organization of the thrombus by connective tissue have
      been reported in detail, in both experimental animal models and in humans, from
      the images obtained by magnetic resonance imaging. Even though we do not yet
      dispose of sensitive enough methods to study the evolution of fat in coronary
      arteries, the high resolution images obtained in carotid or aortic plaques by
      magnetic resonance allow us to visualize the effect produced by statin therapy or
      by other protective maneuvers such as the reduction of LDL levels or the increase
      of HDL levels. Atherosclerotic disease must be considered as a growing tumoral
      process and our main goal should be to determine the degree of malignancy more
      than trying to quantify the stenosis. Therefore, imaging techniques constitute an
      essential instrument to determine the plaque characteristics, and evaluate the
      phase of development to thereby predict the evolution of these lesions.

PMID- 11535183
TI  - [Heart disease, anticoagulants and pregnancy].
AB  - In patients with mechanical prosthetic heart valves, long-term anticoagulant
      therapy is mandatory to prevent thromboembolic phenomena. Anticoagulation is also
      necessary in patients with mitral valvular disease and atrial fibrillation. The
      risk of maternal thromboembolic events is heightened during pregnancy because of
      the patient's hypercoagulable state. Controversy exists concerning the
      appropriate treatment of these patients. No method of anticoagulation is risk
      free. Coumarin derivatives provide adequate protection against thromboembolism
      and should be used during pregnancy in patients with mechanical prostheses. The
      administration of coumarin derivatives in the first trimester is associated with
      an incidence of 26.7% of spontaneous abortion and a risk of 4.1% of coumarin
      embryopathy. Heparin does not cross the placental barrier and it is the obvious
      therapeutic alternative. The teratogenic effects of the coumarinics are prevented
      if these agents are discontinued and replaced by heparin from before the 6th
      until the end of the 12th week of gestation. However, subcutaneous unfractionated
      heparin, in the doses that have been employed, does not provide adequate
      prophylaxis against thromboembolism in these women. In patients treated with
      heparin, the incidence of spontaneous abortion is similar to that observed when
      the mothers are treated with coumarin agents. In order to avoid the delivery of
      an anticoagulated infant, intravenous heparin in full doses, should be
      substituted for the coumarin agent in the last two weeks of gestation.When
      anticoagulant therapy is not necessary, the course of pregnancy in women with
      bioprostheses is similar to that of the general population. However, the short
      duration of tissue valves is a clear disadvantage for these women

PMID- 11535184
TI  - [New aspects in aortic valve disease].
AB  - Renewed interest for aortic valve disease has evolved in recent years. Aortic
      valve replacement has become the second most frequent cause of cardiac surgery,
      following coronary bypass surgery. In addition, the etiologic and
      physiopathologic knowledge of this disorder has improved. In the present paper we
      analyze three aspects of the disease which are, at present, the subject of study
      and controversy: first, we discuss the possible relationship between degenerative
      aortic stenosis and atherosclerosis; second, the involvement of the aortic root
      in cases of bicuspid aortic valve; and third, the surgical indications in
      asymptomatic patients with either aortic stenosis or regurgitation.

PMID- 11535186
TI  - [Transesophageal electrophysiologic study: utility in the diagnosis of syncope].
AB  - Neurocardiogenic and arrhythmic syncope are very common and may be found in many
      patients in Emergency Departments or admitted to hospitals. Technologic advances
      now allow etiologic diagnosis to be determined but the importance of a detailed
      clinical history and physical examination can not be overemphasized in the
      evaluation of syncope, thereby to avoid some costly or invasive procedures. The
      recent introduction of the head-up tilt test alone or in combination with
      electrophysiologic studies, has significantly improved our ability to diagnose
      the etiology of syncope in many cases. Suspicion of an arrhythmic cause of
      syncope does not always require an invasive electrophysiologic study since the
      transesophageal electrophysiologic study is useful and provides a high diagnostic
      yield in the evaluation of non ventricular arrhythmic syncope, such as in the
      sick sinus syndrome, atrio-ventricular block or in supraventricular tachycardia
      and for the study of atrial stability. The transesophageal electrophysiologic
      study is an inexpensive non invasive procedure which does not require complex
      hospitalary installations.

PMID- 11535185
TI  - [Clinical trials on heart failure].
AB  - n 1987 the results of the Consensus study were published, and showed that
      enalapril, an angiotensin convertor enzyme inhibitor (ACEI), was able to modify
      the clinical course of the heart failure syndrome thereby reducing mortality.
      Other ACEI later demonstrated the same effect on the different degrees of
      symptomatic heart failure, left ventricular dysfunction, myocardial infarction
      and more recently in diabetic patients. In 1996 studies on the betablockers
      carvedilol, bisoprolol and metoprolol showed their efficacy in reducing deaths
      due to progressive heart impairment and sudden death in chronic heart failure.
      The RALES study showed that small doses of spironolactone also improved the
      prognosis on this disease. Digital improves the quality of life but not the
      survival rate. Only amiodarone (among the antiarrhythmics) reduces sudden death.
      Other drugs and groups of drugs can not be considered for chronic outpatient
      treatment of heart failure. Multicenter trials make it possible to obtain
      scientific evidence for establishing rational treatments. Many groups of patients
      such as women, elderly people and the more severe cases of the disease are often
      not included in these trials. Occasionally, multicenter trials are badly designed
      (CIBIS and MCD), which in the case of betablockers, led to a substantial delay in
      their administration. Other times, as in the ELITE study, the results were badly
      interpreted. The knowledge obtained from these studies is slow in reaching
      patients, with few patients taking betablockers. It is known that most patients
      do not take the doses found to be effective in multicenter trials.

PMID- 11535187
TI  - [The RISCI registry and the management of myocardial infarction in Spain].

PMID- 11535188
TI  - [The ventricular rapid filling phase: a muscle relaxation or contraction
      process?].

PMID- 11535189
TI  - [Usefulness of the statistical bulletin of deaths to identify extrahospital
      deaths in the context of a myocardial infarction population registry].
AB  - INTRODUCTION AND AIMS: This paper aimed to study the usefulness of the
      Statistical Bulletin of Deaths (SBD) for identifying extrahospital deaths due to
      acute coronary ischaemia, and to determine the most efficient strategy in the
      selection of death causes that appear in the SBD, which are the most efficient
      for the identification. METHODS: Those extrahospital deaths, which, among the
      causes of death, recorded a diagnostic code indicating that they might have been
      caused by coronary ischaemia, were included. To study the usefulness of the death
      certificate we calculated the sensitivity and the positive predictive value of
      cardiac ischaemia. To determine the most efficient strategy for selecting causes
      of death we compared two selection strategies: the first, using only the basic
      cause of death; and the second using all the causes appearing in the SBD.
      RESULTS: Of the 395 SBD selected, 161 were classed as acute heart attacks. In
      those SBD in which cardiac ischaemic disease was given as the basic cause of
      death, we obtained a sensitivity of 82.6% (CI 95%: 75.9-88.1) and a positive
      predictive value of 72.7% (CI 95%: 65.6-79). The most efficient strategy in SBD
      selection proved to be the investigation of death certificates in which cardiac
      ischaemia appeared as one of all the causes of death, and death certificates in
      which the basic cause of death was coded as diabetes mellitus, essential arterial
      hypertension, hypertensive heart disease, cardiac dysrhythmia, and cardiac
      insufficiency. CONCLUSIONS: The information provided by death certificates for
      extrahospital deaths due to coronary ischaemia is reliable. A sensitive and
      efficient SBD selection strategy is proposed for the detection of cases.

PMID- 11535190
TI  - [Elective primary angioplasty in cardiogenic shock: results from a single
      center].
AB  - INTRODUCTION: Cardiogenic shock is the leading cause of death among patients
      hospitalized for acute myocardial infarction. Conventional treatment for acute
      myocardial infarction does not achieve a better outcome in these patients, but
      prior studies with emergency revascularization by coronary angioplasty seem to
      provide encouraging results. PATIENTS AND METHOD: A retrospective study of the
      clinical and angiographic results of elective primary angioplasty in 48 patients
      with cardiogenic shock complicating acute myocardial infarction of less than 12
      hours is described. Intraaortic balloon counterpulsation was used in 79% of the
      patients. Patients with cardiogenic shock secondary to mechanical complications
      were excluded. RESULTS: Angiographic success, defined as a residual stenosis <
      50% and final TIMI flow >/= 2, was achieved in 85% of the culprit lesions, and
      stents were implanted in 76%. Multivessel angioplasty was performed in 25% of the
      patients, and abciximab was used in 35% of the cases. Mean time from the onset of
      symptoms to angioplasty was 7.4 +/- 3.1 hours. In-hospital survival was 58%, and
      was 54% at six months follow-up. CONCLUSIONS: Emergency coronary
      revascularization with primary angioplasty and intracoronary stenting is
      effective in patients with acute myocardial infarction and cardiogenic shock.
      TIMI flow >/= 2 is achieved in most patients, and mortality is reduced when
      compared with conservative treatment in historical series.

PMID- 11535191
TI  - [Incidence and dynamic behavior of spontaneous echocardiographic contrast and
      atrial thrombi in the transplanted heart].
AB  - BACKGROUND: Standard orthotopic heart transplantation produces important anatomic
      and functional atrial alterations with subsequent thrombotic risk. Therefore the
      aim of this study was to analyze the prevalence and evolution of spontaneous
      echocardiography, atrial thrombi and embolic events. PATIENTS AND METHOD: 52
      consecutive transplanted patients were analyzed with transesophageal
      echocardiography and hemodynamic studies performed at 15 days and one year after
      transplantation. RESULTS: Spontaneous echocardiography contrast was present in 27
      patients (52%). Ten atrial thrombi were observed (19.2%), 9 with spontaneous
      echocardiography contrast. Six atrial thrombi appeared on day 15 and 4 after one
      year (with spontaneous echocardiography contrast on the previous study). Using
      multiple logistic regression analysis left atrial size was the only independent
      predictor factor for spontaneous echocardiography contrast (OR = 1.27; 95% CI,
      1.09-1.54) and was an important predictor factor of atrial thrombi formation (OR
      = 1.19; 95% CI, 1.04-1.42). Likewise, the main predictor of atrial thrombi was
      the presence of spontaneous echocardiography contrast (OR = 116; 95% CI, 8.4
      999). The hemodynamic pattern did not predict either the presence of spontaneous
      echocardiography contrast or atrial thrombi. The global incidence of embolic
      events was 4% less than previously described. CONCLUSIONS: The incidence of
      atrial thrombi and spontaneous echocardiographic contrast after standard
      orthotopic heart transplantation was 19.2% and 52%, respectively. An enlarged
      atrium and/or spontaneous echocardiography contrast was found to increase the
      risk of atrial thrombi. Considering the dynamic nature of atrial thrombi
      formation, periodical transesophageal echocardiography studies are recommended
      after heart transplantation.

PMID- 11535192
TI  - [Clinical Characteristics and Evolution of Recurrent Infectious Endocarditis in
      non Drug Addicts].
AB  - INTRODUCTION AND OBJECTIVES: Recurrence of infection is observed in a high
      proportion of patients who have had infective endocarditis in the past. The aim
      of our study was to evaluate the possible differences between the first and the
      recurrent episodes of endocarditis, as well as to assess the outcome and
      prognosis of patients with recurrent endocarditis. PATIENTS AND METHOD: We
      reviewed a series of 13 episodes of recurrent endocarditis from among 196 cases
      of infective endocarditis involving non-drug-addict patients in two hospitals
      from 1987 to 2000. RESULTS: There were no differences between recurrent and first
      episodes of endocarditis according to age, sex, heart valve involved or causal
      microorganisms. Prosthetic valve endocarditis was more common in patients with
      recurrent endocarditis (86% versus 27%; p < 0.001). Although there were no
      differences in the rate of complications or early surgery, overall mortality was
      significantly higher in patients with recurrent endocarditis (53% versus 27%: p <
      0.05). When early and late mortality were analysed separately, the differences
      did not achieve significance. CONCLUSIONS: Recurrent endocarditis was frequent in
      our series (7% of all cases). The features were similar to those of the first
      episode except for a higher rate of prosthetic valve endocarditis and a higher
      overall mortality.

PMID- 11535193
TI  - [Low-molecular weight heparins in the prophylaxis and treatment of pulmonary
      thromboembolism].

PMID- 11535198
TI  - Numerical modelling of the perturbation of HIV-1 during combination anti
      retroviral therapy.
AB  - A competitive, chaos-free, implicit, finite-difference method is developed and
      used for a novel deterministic model for the perturbation of HIV by combination
      antiretroviral therapy. The compartmental model monitors the interaction between
      HIV and CD4(+) T cells, its principal target and site of replication in vivo, in
      the presence of reverse transcription inhibitors and protease inhibitors. The
      model exhibits two steady states, an uninfected (trivial) steady state (with no
      virus present) and an endemically infected state (with virus and infected T cells
      present). Stability and bifurcation analyses together with numerical simulations
      of the resulting dynamical system are reported.

PMID- 11535199
TI  - Design and implementation of an immune system simulator.
AB  - Cellular automata based models have proven capable of providing several new
      insights into the dynamics of the immune system (IS) response.A qualitative
      picture of the IS behavior can be obtained with small-scale simulations. However,
      for a more detailed analysis and to further validate the models, large-scale
      simulations are required. To this purpose we present here a simulator (PARIMM) of
      the IS response which has been carefully designed and coded to allow such
      simulations (millions of cells with a very high degree of complexity). The code
      does not just resort to parallel processing to run faster. Data structures and
      I/O have been optimized as well to limit the (huge) memory and disk space
      requirements. The recent addition of the description of the T killer cellular
      mediated response allows the code to simulate both humoral and cellular immune
      reactions. All these features put PARIMM among the most complete simulators of
      the immune system developed up today.

PMID- 11535200
TI  - Virtual reality orthopedic surgery simulator.
AB  - This paper describes a highly interactive virtual reality orthopedic surgery
      simulator. The simulator allows surgeons to use various surgical instruments to
      operate on virtual rigid anatomic structures, such bones, prostheses and bone
      grafts, to simulate every procedure on the rigid structures for complex
      orthopedic surgeries, including arthroplasty, corrective or open osteotomy, open
      reduction of fractures and amputation. A comparative study of the simulator with
      paper simulation was performed and showed that interns and residents found the
      simulator to be a useful learning tool, and that visiting doctors could use it
      effectively for planning verification and rehearsal of operations.

PMID- 11535201
TI  - Pressure-based simultaneous CFR and FFR measurements: understanding the
      physiology of a stenosed vessel.
AB  - Arterial stenosis is known to be one of the most serious cardiovascular diseases.
      Angiographical estimation of arterial stenosis provides limited information on
      the severity of the occlusion and the flow of blood through it. Hemodynamical
      assessment of the flow and pressure behaviour, is known to be clinically
      important. Hemodynamically based parameters, such as pressure based myocardial
      fractional flow reserve (FFR) and the flow based coronary flow reserved (CFR)
      were introduced to provide a much better tool for treating arterial diseases. We
      have developed a new method for simultaneous measurement of pressure-derived CFR
      and FFR. The advantage of pressure derived hemodynamic parameters is very
      substantial, and its relatively straightforward application in clinical setting
      is solid. The method has been validated by means of a computational fluid
      dynamics (CFD) model of the arterial stenosis and in vitro bench studies.

PMID- 11535202
TI  - Computational particle-hemodynamics analysis and geometric reconstruction after
      carotid endarterectomy.
AB  - Transient three-dimensional laminar incompressible dilute suspension flow in
      rigid in-plane carotid artery bifurcations has been solved with a user-enhanced
      finite-volume program. Instantaneous velocity vector and wall shear stress vector
      fields illustrate strong "disturbed flow" patterns. Implications of elevated
      surface contours of hemodynamic wall parameters, indicating such disturbed flows,
      and particle deposition sites are discussed and a relative comparison in terms of
      indicator functions between the endarterectomized carotid artery bifurcation and
      two design improvements is shown. Although the combined perioperative mortality
      and non-fatal stroke rate for carotid endarterectomy ranges only from 2% to 7%,
      the final geometric design recommendation presented merits consideration because
      it may significantly lower the chances of post-operative complications such as
      stroke, ischemic attack, or even death. The new carotid artery bifurcation design
      is based on the overall reduction of "disturbed flow" indicator functions,
      including the time-averaged wall shear stress angle deviation and a wall
      deposition parameter for critical blood particles, such as monocytes.

PMID- 11535203
TI  - On preprocessing of protein sequences for neural network prediction of
      polyproline type II secondary structures.
AB  - Polyproline type II stretches are somewhat rare on proteins. The backbone of this
      secondary structural element folds to a triangular form instead of the normal
      alpha-helix with 3.6 residues per turn. It is a very challenging task to try to
      detect them computationally from protein sequence. Here, we have studied the
      preprocessing phase in particular, which is important for any machine learning
      method. Preprocessing included selection of relevant data from the Protein Data
      Bank and investigation of learnability properties. These properties show whether
      the material is suitable for neural network computing. The complexity of
      algorithms in connection with preprocessing was briefly considered. We found that
      feedforward perceptron neural networks were appropriate for the prediction of
      polyproline type II and also relatively efficient in this task. The problem is
      very difficult because of the great similarity of the two classes present in the
      classification. Nevertheless, neural networks were able to recognize and predict
      about 75% of secondary structures.

PMID- 11535204
TI  - The use of the Hilbert transform in ECG signal analysis.
AB  - This paper presents a new robust algorithm for QRS detection using the first
      differential of the ECG signal and its Hilbert transformed data to locate the R
      wave peaks in the ECG waveform. Using this method, the differentiation of R waves
      from large, peaked T and P waves is achieved with a high degree of accuracy. In
      addition, problems with baseline drift, motion artifacts and muscular noise are
      minimised. The performance of the algorithm was tested using standard ECG
      waveform records from the MIT-BITH Arrhythmia database. An average detection rate
      of 99.87%, a sensitivity (Se) of 99.94% and a positive prediction (+P) of 99.93%
      have been achieved against study records from the MIT-BITH Arrhythmia database. A
      detection error rate of less than 0.8% was achieved in every study case. The
      reliability of the proposed detector compares very favorably with published
      results for other QRS detectors.

PMID- 11535205
TI  - Use of the name "Progestin".

PMID- 11535206
TI  - Multicenter, comparative study of cycle control, efficacy and tolerability of two
      low-dose oral contraceptives containing 20 microg ethinylestradiol/100 microg
      levonorgestrel and 20 microg ethinylestradiol/500 microg norethisterone.
AB  - A comparison of cycle control, efficacy and tolerability of two oral
      contraceptive preparations containing 20 microg ethinylestradiol combined with
      either 100 microg levonorgestrel (EE/LNG 20/100) or 500 microg norethisterone
      (EE/NET 20/500) was conducted. These results were compared to a standard
      reference preparation, containing 30 microg ethinylestradiol combined with 150
      microg levonorgestrel (EE/LNG 30/150). Efficacy data from 8,544 treatment cycles
      were obtained from 767 women. Good cycle control and effective contraception was
      achieved with the two LNG preparations, however, the cycle control results were
      less favorable with EE/NET 20/500. The cumulative incidence of women with at
      least one episode of intermenstrual bleeding from cycles 2 to 7 (primary target
      variable) was 43.9% for EE/LNG 20/100, 72.7% for EE/NET 20/500, and 15.7% for the
      standard EE/LNG 30/150. The difference between the 2 20 microg of EE
      preparations, which favored EE/LNG 20/100, was statistically significant (p =
      0.001). The overall spotting rates (cycles 1-13) were 9.3% for EE/LNG 20/100,
      21.7% for EE/NET 20/500, and 3.3% for the standard EE/LNG 30/150. Amenorrhea was
      reported in 7.1% (EE/LNG 20/100), 20.6% (EE/NET 20/500), and 0.9% (standard
      EE/LNG 30/150), respectively. Intermenstrual bleeding episodes were shorter with
      EE/LNG 20/100 and EE/LNG 30/150 of the 13 treatment cycles. The study Pearl
      indices were 0.9 for EE/LNG 20/100, 1.9 for EE/NET 20/500, and 0.0 for EE/LNG
      30/150. All three treatments were well tolerated. However, tolerability was
      somewhat less favorable with EE/NET 20/500. A total of 160 women prematurely
      discontinued the study for various reasons (EE/LNG 20/100: 7%; EE/NET 20/500:
      18%; EE/LNG 30/150: 4%). The overall adverse event incidence rate during the
      trial was low in all groups. Blood pressure remained largely unaffected. Thirteen
      serious adverse events were recorded for all treatment groups, all but one were
      assessed as not related to the treatments. There were no remarkable treatment
      related differences in mean body weight throughout the study and the laboratory
      values were largely unaffected in all three treatments groups.

PMID- 11535208
TI  - Levonorgestrel-only emergency contraception: real-world tolerance and efficacy.
AB  - Levonorgestrel-only emergency contraception was introduced onto the market in
      France in May 1999 on the heels of a large-scale clinical trial demonstrating its
      enhanced efficacy and tolerance over the combined estrogen-progestin reference
      method. To evaluate the product's real-world tolerance and efficacy in the more
      than 20 months that it has been on the market, a retrospective study was
      performed among large-scale prescribers in France. One hundred physicians were
      asked to complete a written questionnaire outlining their practices with regards
      to their prescription of the product as well as their knowledge and evaluation of
      the product's tolerance and efficacy. Results from 82 respondents representing
      over 2,000 administrations demonstrate that physicians judge levonorgestrel-only
      emergency contraception to be very well tolerated and without unexpected side
      effects. Further, respondents report a pregnancy rate similar to that chronicled
      in the large-scale clinical trial (less than 3%), thus substantiating conclusions
      regarding the product's considerable efficacy and its potential for reducing the
      rate of unintended pregnancies.

PMID- 11535207
TI  - Effects of two low-dose oral contraceptives containing ethinylestradiol and
      either desogestrel or levonorgestrel on serum lipids and lipoproteins with
      particular regard to LDL size.
AB  - This study was designed to determine the effects of two low-dose oral
      contraceptives, most frequently given in our area, monophasic
      desogestrel/ethinylestradiol (DG/EE) and triphasic
      levonorgestrel/ethinylestradiol (LNG/EE), on lipoprotein parameters, especially
      LDL particle size and HDL subclass distribution (determined by lipid-stained 2%
      20% polyacrylamide gradient gel electrophoresis) in 37 healthy normolipidemic
      women aged 19 to 27 years. Lipid and lipoprotein parameters were measured before
      the start of treatment and in the third month of oral contraceptive use. Results
      reflected the estrogen-progestin balance. As compared with baseline values, with
      both formulations, plasma total cholesterol, phospholipids, and HDL3 cholesterol
      increased, and LDL-predominant peak size decreased, with a translation of LDL
      pattern A towards pattern I. With DG/EE, plasma triglycerides, apolipoproteins AI
      and B increased. With LNG/EE, LDL cholesterol increased, and HDL2 cholesterol
      decreased. All these modifications were moderate, within threshold limits.
      Estrogen-dominant monophasic DG/EE appears to be more favorable than progestin
      dominant triphasic LNG/EE, since the reduction in LDL-predominant peak size is
      not associated with an increase in LDL cholesterol or with a decrease in HDL2
      cholesterol.

PMID- 11535209
TI  - Young women requesting emergency contraception are, despite contraceptive
      counseling, a high risk group for new unintended pregnancies.
AB  - Since its introduction in Sweden in 1994, emergency contraception has become a
      welcome addition to the campaign against unwanted pregnancy. In addition to an
      unplanned pregnancy, unprotected sexual intercourse may also involve the risk of
      contracting sexually transmitted diseases (STD). The aim of this study was to
      assess the short- and long-term risk of unintended pregnancy and to determine the
      frequency of chlamydia infections in women receiving emergency contraception.
      Between September 1998 and February 1999 young women aged 15-25 years had the
      opportunity to obtain emergency contraception (Yuzpe method) at a youth clinic in
      the city of Orebro where the opening hours were extended to include Saturdays and
      Sundays. A follow-up visit 3 weeks after treatment, which included contraceptive
      counseling, was offered to all participants. At both visits, a pregnancy test and
      a chlamydia test were performed, and the women completed a questionnaire. After
      the initial visit, the young women where monitored for new pregnancies during the
      following 12 months. One pregnancy occurred in the 134 young women who received
      emergency contraception during the study period. None of the women had a positive
      chlamydia test. Of those requesting emergency contraception, 54% did so because
      no contraception was used, 32% because of a ruptured condom, 11% because of
      missed oral contraceptives (OC), and 5% had mixed reasons. At long-term follow-up
      1 year after the initial visit, 10 of the 134 young women had experienced an
      unplanned pregnancy that terminated in legal abortion in 9 women. All these women
      had either started and terminated OC or had never commenced the prescribed OC.
      Young women who request emergency contraception are, despite a planned follow-up
      with contraceptive counseling, a high risk group for new unintended pregnancies.
      In Sweden they do not seem to be a high risk group for STD.

PMID- 11535210
TI  - Second trimester medical abortion with mifepristone and gemeprost: a review of
      956 cases.
AB  - The treatment outcomes of 956 women undergoing second trimester termination of
      pregnancy with mifepristone and gemeprost were studied. The median gestational
      age was 16 weeks (range: 12-24 weeks). All women were treated with 200 mg
      mifepristone orally, followed 36 h later with 1 mg vaginal gemeprost administered
      every 6 h to a maximum of 4 doses in the first 24 h. A second course of 1 mg
      vaginal gemeprost was given 3-hourly in the next 12 h, if abortion had not
      occurred. Overall, 96.4% and 98.8% of the women aborted within 24 and 36 h,
      respectively. The median induction-to-abortion interval was 7.8 h (range: 0.5
      109.9 h). The induction-abortion interval was longer in nulliparous women and
      women with a gestation age 17 weeks or above. Surgical evacuation of the uterus
      was performed in 11.5% of women for incomplete abortion or retained placenta.
      More multiparous women (16.7%) required surgical evacuation of uterus than did
      nulliparous women (7.3%; p <0.001). Ten (0.1%) women failed to abort with
      gemeprost and required other methods for abortion. In conclusion, a combination
      of mifepristone and gemeprost is a safe, effective, and noninvasive method of
      medical abortion for second trimester pregnancy.

PMID- 11535211
TI  - Risk factors for intrauterine device failure: a review.
AB  - After reviewing the literature on intrauterine devices (IUDs) published over the
      last 30 years, we selected and analyzed recent and most relevant (with
      appropriate methodology design) articles dealing with the risk factors for IUD
      failure. There is sufficient evidence to conclude that the TCu380 and
      levonorgestrel-releasing (LNG) IUD are the most effective, with a cumulative
      pregnancy rate of less than 2% at 12 years for the TCu380 and around 1% for the
      LNG IUD at 7 years. In addition, advancing age increases IUD effectiveness, and
      displacement of the IUD decreases effectiveness. The IUDs with the highest copper
      concentrations are clearly less prone to failure than those with lower copper
      concentrations.

PMID- 11535212
TI  - Use of Norplant implants in the immediate postpartum period among asymptomatic
      HIV-1-positive mothers.
AB  - A prospective cohort study of Norplant use in the immediate postpartum period
      among asymptomatic HIV-1-positive women was conducted in Bangkok, Thailand. The
      objectives of this study were to evaluate side effects and menstrual patterns of
      the Norplant system in this group. A total of 88 asymptomatic HIV-1-positive
      mothers were recruited for this study. All of them voluntarily accepted the use
      of the Norplant implant as a contraceptive method immediately postpartum. Their
      mean age was 24.9 years. Most of them had completed primary school. The follow-up
      period was 24 weeks. There were eight participants lost from the study because of
      loss of contact. Irregular bleeding was the most common menstrual pattern in
      these participants. The major side effects were headache, followed by hair loss.
      No subject terminated Norplant use during the study period. The Norplant implant
      appears to be safe and well tolerated in asymptomatic HIV-1-positive parturients
      when inserted immediately postpartum.

PMID- 11535213
TI  - Levonorgestrel concentrations during 7 years of continuous use of Jadelle
      contraceptive implants.
AB  - Serum levonorgestrel concentrations were assayed in a multicenter, 7-year study
      of 199 users of Jadelle rod implants. We examined drug levels, patterns of
      changes, factors affecting drug levels, and concentrations at which pregnancies
      occurred. Mean levonorgestrel concentrations declined from 435 pg/mL at 1 month
      of use to 64% of that value (280 pg/mL) at the end of 3 years. Between the end of
      the third and fifth years neither mean nor median serum levels varied markedly.
      At 5 years the mean concentration was again 64% of the first month's mean.
      Declining levels were observed thereafter through the end of 7 years when the
      mean, 224 pg/mL, was 52% of the 1-month value. Last measured drug concentrations
      of women who became pregnant during Jadelle use had mean and median values of 152
      and 144 pg/mL, respectively, and a maximum value of 180 pg/mL. Analyses indicated
      ponderal index, body weight, duration of use, and a single clinical center were
      the most important variables affecting measured levonorgestrel levels.
      Approximately one-third of assays in the sixth and seventh years were found to be
      below 180 pg/mL, suggesting that Jadelle levonorgestrel implants would not
      maintain sufficiently high levels of effectiveness against pregnancy after 5
      years and that heavier women would then be at greater risk of pregnancy.

PMID- 11535214
TI  - A prospective study of the effects of oral contraceptives on sexuality and well
      being and their relationship to discontinuation.
AB  - The purpose of the study was to explore predictors of discontinuation of oral
      contraceptives (OC) including pre-OC use characteristics and adverse physical,
      emotional, and sexual effects of OCs. Women aged 18+ years in committed, sexually
      active relationships were assessed before starting OC and reassessed at 3, 6, and
      12 months or shortly after discontinuation. Assessment included pre-OC use
      attitudes and expectations about the pill; self-reported side effects and
      perimenstrual symptoms including premenstrual syndrome (PMS); physical and
      emotional well-being; and sexual interest, enjoyment, and frequency of sexual
      activity. Seventy-nine women completed the study, 38% continued OCs, 47%
      discontinued, and 14% switched to another OC. Emotional side effects, worsening
      of PMS, decreased frequency of sexual thoughts, and decreased psychosexual
      arousability correctly categorized 87% of cases by using logistic regression.
      Emotional and sexual side effects were the best predictors of
      discontinuation/switching, yet such OC effects have been largely ignored in the
      research literature.

PMID- 11535215
TI  - Testosterone for male contraception during one year: attitudes, well-being and
      quality of sex life.
AB  - Men's attitudes, well-being, and sex life were studied during 1 year's use of
      testosterone contraception. A consecutive series of 25 men were followed by
      structured interviews at baseline, during the efficacy phase of oligo-azoospermia
      and after recovery. Open questions gave qualitative aspects on male
      contraception. Themes obtained were expectations about freedom and control over
      their reproduction (16/25) and an enhanced sex life (17/25). The method was rated
      to be as expected or better by the great majority. Health and most aspects of the
      men's sex life did not change, but the frequency of intercourse and the quality
      of sex life in general were higher (p = 0.001 and p = 0.006, respectively) during
      the efficacy phase compared to the recovery phase. The decrease during recovery
      phase may be explained by a pharmacological down-regulation of the androgen
      receptors. Eight of 22 men admitted slightly aggressive feelings during
      treatment. Five of 11 women reported the men as more self-assertive during the
      efficacy phase.

PMID- 11535216
TI  - Properties of a new acid-buffering bioadhesive vaginal formulation (ACIDFORM).
AB  - Vaginal prophylactic methodology may prevent heterosexual transmission of the HIV
      and other sexually transmitted disease-causing organisms as well as unplanned
      pregnancies. A new delivery system (ACIDFORM) was designed with acid-buffering,
      bioadhesive, and viscosity-retaining properties to (1) maintain the acidic
      vaginal milieu (the low pH inactivates many pathogens and spermatozoa), (2) form
      a protective layer over the vaginal/cervical epithelium (minimizing contact with
      pathogenic organisms), and (3) provide long-term vaginal retention. A Phase I
      clinical study with ACIDFORM provided initial information about its safety and
      showed the formation of a layer over the vaginal/cervical epithelium [1; Amaral
      et al., Contraception 1999;60:361-6]. To study the properties of the gel (without
      active ingredient) in more detail, ACIDFORM's acid-buffering, bioadhesive,
      viscosity-retaining, and spermicidal properties were compared in vitro to
      marketed formulations, and its long-term stability was assessed. ACIDFORM, either
      when titrated with NaOH or when mixed directly with semen, is highly acid
      buffering and much more effective than Aci-Jel, a commercial acid-buffering
      vaginal product. ACIDFORM adheres well to two model membranes (excised sheep
      vagina and cellophane) and is more bioadhesive than Conceptrol, Advantage S,
      Replens, Aci-Jel, and K-Y jelly. On dilution, ACIDFORM also retains its viscosity
      better than these marketed products. ACIDFORM is spermicidal and is stable for at
      least 2 years. These results suggest that ACIDFORM has advantages over presently
      marketed vaginal delivery systems. The gel may either be useful by itself as an
      antimicrobial contraceptive product or as a formulation vehicle for an active
      ingredient with antimicrobial and/or contraceptive properties.

PMID- 11535227
TI  - Bayesian analysis: what does it add to studies of the natural history of MS?

PMID- 11535228
TI  - The motor unit and electromyography--the legacy of Derek Denny-Brown.
AB  - With the development of the concept of the motor unit and new recording
      instruments, single motor unit action potentials (MUAPs) were recorded in 1929 in
      man by Adrian and Bronk and in the experimental animal by Denny-Brown. Studies of
      MUAPs in patients with neuromuscular disease followed, and in 1938, Denny-Brown
      and Pennybacker laid the foundation for clinical electromyography (EMG). Action
      potentials of single contracting or spontaneously firing motor units, termed
      fasciculations, were recorded and separated from the action potentials of single
      denervated muscle fibers, termed fibrillations. Thus, it was possible to
      interpret muscle twitching and cramping by EMG and separate neurogenic from
      myopathic diseases. Since then, EMG and neuromuscular disease have expanded
      greatly providing greater diagnostic capability and therapeutic success.

PMID- 11535229
TI  - Predicting secondary progression in relapsing-remitting multiple sclerosis: a
      Bayesian analysis.
AB  - With the aid of a Bayesian statistical model of the natural course of relapsing
      remitting Multiple Sclerosis (MS), we identify short-term clinical predictors of
      long-term evolution of the disease, with particular focus on predicting onset of
      secondary progressive course (failure event) on the basis of patient information
      available at an early stage of disease. The model specifies the full joint
      probability distribution for a set of variables including early indicator
      variables (observed during the early stage of disease), intermediate indicator
      variables (observed throughout the course of disease, prefailure) and the time to
      failure. Our model treats the intermediate indicators as a surrogate response
      event, so that in right-censored patients, these indicators provide supplementary
      information pointing towards the unobserved failure times. Moreover, the full
      probability modelling approach allows the considerable uncertainty which affects
      certain early indicators, such as the early relapse rates, to be incorporated in
      the analysis. With such a model, the ability of early indicators to predict
      failure can be assessed more accurately and reliably, and explained in terms of
      the relationship between early and intermediate indicators. Moreover, a model
      with the aforementioned features allows us to characterize the pattern of disease
      course in high-risk patients, and to identify short-term manifestations which are
      strongly related to long-term evolution of disease, as potential surrogate
      responses in clinical trials. Our analysis is based on longitudinal data from 186
      MS patients with a relapsing-remitting initial course. The following important
      early predictors of the time to progression emerged: age; number of neurological
      functional systems (FSs) involved; sphincter, or motor, or motor-sensory
      symptoms; presence of sequelae after onset. During the first 3 years of follow
      up, to reach EDSS> or =4 outside relapse, to have sphincter or motor relapses and
      to reach moderate pyramidal involvement were also found to be unfavourable
      prognostic factors.

PMID- 11535230
TI  - Neurophysiological evidence of spared upper motor conduction fibers in clinically
      complete spinal cord injury: discomplete SCI in rats.
AB  - Motor evoked potentials (MEP) were recorded and characterized by epidural
      electrodes (scMEP) and extracellular microelectrodes (exMEP) on T(13) level from
      10 normal rats and 40 rats with chronic spinal cord injury (SCI). The spinal cord
      of 40 anesthetized rats were injured with various severity (sham, 35, 70, and 100
      g/cm impact injury) at T(8)-T(9) cord using Allen's drop model. The incline plane
      and Tarlov techniques were investigated to assess clinical neurological function.
      MEPs in the normal rats elicited by applying transcortical suprathreshold
      stimulation consisted of 3-4 early negative peaks (N(1), N(2), N(3), N(4))
      followed by several late waves. The N(1) and N(2) peaks had their maximal
      amplitudes in the anterior and ventrolateral funiculus, respectively,
      irrespective of the polarity of stimulation, which indicated that these impulses
      were conducted mostly through the extrapyramidal pathways. The 100 g/cm impact
      injury or transection of the cord caused abolishment of the MEP signals distal to
      the lesion, whereas the 35 g/cm injury resulted in a latency shift and amplitude
      decrement of the MEP peaks. Out of 20 rats with 70 g/cm injuries, 18 showed
      clinically paraplegia. Among them, seven had neurophysiological evidence of
      residual conduction pathways through the injured cord segment, such as the
      presence of N(1) and N(2) peaks in scMEP or exMEP. After 4-aminopyridine (4-AP)
      administration (1 mg/kg), the amplitude of spared exMEP increased significantly
      and spread more widely. These results suggest that MEPs evoked by transcortical
      stimulation travel mostly in the extrapyramid tract. The present study provides
      further direct and objective electrophysiological evidences of spared functional
      axons after discomplete SCI, since many other studies on this field have achieved
      similar results previously. Furthermore, pharmaceutical treatment with 4-AP or
      other K(+) channel blocking agents proved to be a potential therapeutic strategy
      for patient with chronic SCI.

PMID- 11535231
TI  - Laminin alpha 2 (merosin)-deficient muscular dystrophy and demyelinating
      neuropathy in two cats.
AB  - We report laminin alpha 2 (merosin) deficiency associated with muscular dystrophy
      and demyelinating neuropathy in two cats. The cats developed progressive muscle
      weakness, and atrophy. Either hypotonia or contractures resulted in recumbency,
      necessitating euthanasia. Muscle biopsies showed dystrophic changes including
      marked endomysial fibrosis, myofiber necrosis, variability of fiber size, and
      perimysial lipid accumulation. Immunohistochemistry showed that laminin alpha 2
      chain was absent or reduced, while dystrophin and all the components of the
      dystrophin-associated glycoprotein complex were present and normal. One cat was
      examined in detail. Motor nerve conduction velocity (MNCV) was decreased, and
      ultrastructurally the peripheral nerves showed Schwann cell degeneration and
      demyelination. Brain imaging was not performed, but white matter changes were not
      apparent in the brain at necropsy. The disease in these cats is similar to
      primary or secondary merosin (laminin alpha 2)-deficient congenital muscular
      dystrophy (CMD) in humans and to dystrophia muscularis in mice.

PMID- 11535232
TI  - A novel SOD1 gene mutation in familial ALS with low penetrance in females.
AB  - We identified a novel missense mutation in the Cu/Zn superoxide dismutase gene in
      a family with amyotrophic lateral sclerosis (ALS). The mutation was a transition
      of T to C, resulting in a substitution of leucine 126 to serine in exon 5. The
      family had very unique clinical features of extremely mild severity only in the
      legs of two male patients with onset of 42 and 52 years old, and their mothers
      did not develop any symptom even after reaching the age of 80 and carrying the
      same mutation. The present study suggests that there are other factors that delay
      or prevent the disease.

PMID- 11535233
TI  - Therapeutic benefit of intracerebral transplantation of bone marrow stromal cells
      after cerebral ischemia in rats.
AB  - We tested the hypothesis that bone marrow stromal cells (MSCs) transplanted into
      the ischemic boundary zone, survive, differentiate and improve functional
      recovery after middle cerebral artery occlusion (MCAo). MSCs were harvested from
      adult rats and cultured with or without nerve growth factor (NGF). For cellular
      identification, MSCs were prelabeled with bromodeoxyuridine (BrdU). Rats (n=24)
      were subjected to 2 h of MCAo, received grafts at 24 h and were euthanized at 14
      days after MCAo. Test groups consisted of: (1) control-MCAo alone (n=8); (2)
      intracerebral transplantation of MSCs (n=8); (3) intracerebral transplantation of
      MSCs cultured with NGF (n=8). Immunohistochemistry was used to identify cells
      from MSCs. Behavioral tests (rotarod, adhesive-removal and modified neurological
      severity score [NSS]) were performed before and after MCAo. The data demonstrate
      that MSCs survive, migrate and differentiate into phenotypic neural cells.
      Significant recovery of somatosensory behavior (p<0.05) and NSS (p<0.05) were
      found in animals transplanted with MSCs compared with control animals. Animals
      that received MSCs cultured with NGF displayed significant recovery in motor
      (p<0.05), somatosensory (p<0.05) and NSS (p<0.05) behavioral tests compared with
      control animals. Our data suggest that intracerebral transplantation of MSCs may
      provide a powerful autoplastic therapy for stroke.

PMID- 11535234
TI  - Heterogeneous immunogenetic background in Japanese adults with myasthenia gravis.
AB  - The aim of this study was to elucidate the roles of human leukocyte antigen (HLA)
      class II genes in disease susceptibility in Japanese adult patients with
      myasthenia gravis (MG). A number of studies have shown that MG is correlated with
      DR3 in Caucasians. In Japanese, infantile MG is associated with DR9, but the HLA
      class II alleles associated with adult MG remains unclear. HLA-DRB1 and DQB1
      alleles were determined by genotyping in 75 Japanese adult patients with MG and
      in 115 race-matched healthy adults. No statistically significant difference was
      observed in the overall prevalences of DRB1 and DQB1 alleles between MG patients
      and healthy controls, even when the patients and controls were stratified on the
      basis of their gender. MG patients with DQB1*0604 were younger and those with
      DQB1*0402 were older at disease onset than those without (P=0.03 and 0.008,
      respectively). Concomitant autoimmune thyroid disease was associated with
      DRB1*0803 (P=0.0009, corrected P=0.04). In addition, anti-acetylcholine receptor
      antibody levels were significantly higher in patients with DQB1*0604 than in
      those without (P=0.045). These findings indicate that immunogenetic backgrounds
      in Japanese adult MG patients are heterogeneous and are apparently different from
      those in Caucasian patients.

PMID- 11535235
TI  - Expression of metabotropic glutamate receptor mRNAs in the human spinal cord:
      implications for selective vulnerability of spinal motor neurons in amyotrophic
      lateral sclerosis.
AB  - To elucidate the relevance of metabotropic glutamate receptors (mGluRs) to the
      selective vulnerability of motor neurons in the spinal cord in patients with
      amyotrophic lateral sclerosis (ALS), we investigated the distribution of mRNAs
      coding mGluR1-5 in the normal human spinal cord. The mRNAs for mGluR1, 4 and 5
      were observed in the spinal gray matter, whereas mGluR2 mRNA was absent in the
      spinal cord and mGluR3 mRNA was displayed only on glial cells in the white
      matter. Signals for mGluR1 and mGluR5 were enriched in the dorsal horn, while
      mGluR4 mRNA was abundant in the ventral horn. Since agonists to group I mGluRs
      (mGluR 1 and 5) have been demonstrated to have neuroprotective effects on spinal
      motor neurons, less expression of mRNAs coding mGluR1 and mGluR5 in the ventral
      horn than in the dorsal horn may be implicated in the selective susceptibility of
      spinal motor neurons in ALS.

PMID- 11535236
TI  - Opsoclonus in three dimensions: oculographic, neuropathologic and modelling
      correlates.
AB  - Opsoclonus is a dyskinesia consisting of involuntary, arrhythmic, chaotic,
      multidirectional saccades, without intersaccadic intervals. We used a magnetic
      scleral search coil technique to study opsoclonus in two patients with
      paraneoplastic complications of lung carcinoma. Eye movement recordings provided
      evidence that opsoclonus is a three-dimensional oscillation, consisting of
      torsional, horizontal, and vertical components. Torsional nystagmus was also
      present in one patient. Antineuronal antibody study revealed the presence of anti
      Ta (Ma2 onco-neuronal antigen) antibodies in one patient, which had previously
      been associated only with paraneoplastic limbic encephalitis and brainstem
      dysfunction, but not opsoclonus, and only in patients with testicular or breast
      cancer. Neuropathologic examination revealed mild paraneoplastic encephalitis.
      Normal neurons identified in the nucleus raphe interpositus (rip) do not support
      postulated dysfunction of omnipause cells in the pathogenesis of opsoclonus.
      Computer simulation of a model of the saccadic system indicated that
      disinhibition of the oculomotor region of the fastigial nucleus (FOR) in the
      cerebellum can generate opsoclonus. Histopathological examination revealed
      inflammation and gliosis in the fastigial nucleus. This morphological finding is
      consistent with, but not necessary to confirm, damage to afferent projections to
      the FOR, as determined by the model. Malfunction of Purkinje cells in the dorsal
      vermis, which inhibit the FOR, may cause opsoclonus by disinhibiting it.

PMID- 11535237
TI  - Epidermal growth factor and platelet-derived growth factor induce expression of
      Egr-1, a zinc finger transcription factor, in human malignant glioma cells.
AB  - Amplification and/or mutations of the epidermal growth factor (EGF) receptor have
      been frequently reported in human malignant gliomas, the most common primary
      tumor of the adult central nervous system. We have analyzed a panel of
      established human glioma cell lines for EGF receptor expression. The EGF receptor
      was expressed in all of the glioma cell lines tested, with highest levels found
      in the cell line U343MG-a. In addition, various amounts of a truncated form of
      the EGF receptor were detected. The platelet-derived growth factor (PDGF) alpha
      receptor, analyzed for comparison, was expressed at low levels in human glioma
      cells, with the exception of U-118MG and U-373MG cells. The truncated form of the
      EGF receptor has been discussed as a constitutively active variant of the
      receptor. Using antibodies directed against the active form of the EGF receptor,
      we show here that the truncated variant of the EGF receptor in U343MG-a cells is
      not in the active conformation. However, the full-length EGF receptor, highly
      expressed in U343MG-a cells, was very rapidly activated following EGF treatment.
      In line with this, phosphorylation and activation of the mitogen-activated
      protein kinase/extracellular signal-regulated protein kinase (ERK) in U343MG-a
      cells required administration of EGF. Moreover, using highly specific riboprobes
      we observed that EGF signaling increased the Egr-1 mRNA concentration in human
      glioma cells within 30 min. The increase in the Egr-1 mRNA concentration was
      followed by a transient synthesis of the Egr-1 protein. Likewise, Egr-1 mRNA and
      protein concentrations were increased in U-118MG and U-373MG cells treated with
      PDGF. The synthesis of Egr-1 in human glioma cells as a result of EGF or PDGF
      stimulation indicates that Egr-1 may be an important "late" part of the EGF and
      PDGF-initiated signaling cascades suggesting that Egr-1 functions as a "third
      messenger" in glioma cells connecting growth factor stimulation with changes in
      gene transcription.

PMID- 11535238
TI  - Preclinical cognitive decline in late middle-aged asymptomatic apolipoprotein E
      e4/4 homozygotes: a replication study.
AB  - In a previous cross-sectional study of 100 asymptomatic individuals aged 49-69,
      we reported age-related decline in immediate and delayed memory that was steeper
      in apolipoprotein E (apoE)-e4/4 homozygotes than in members of other genetic
      subgroups. These findings were preliminarily based upon the statistical problem
      of multiple comparisons. We therefore sought to replicate these findings in a new
      cohort. From 1998 to 2000, 80 asymptomatic residents of Maricopa County, AZ were
      recruited through newspaper ads. 20 apoE-e4/4 homozygotes, 20 e3/4 heterozygotes,
      and 40 e4 noncarriers were matched (1:1:2) by age, gender, and years of
      education. All had normal neurologic and psychiatric examinations, including
      Folstein minimental status exam (MMSE) and Hamilton depression scale, and
      underwent a battery of neuropsychological tests identical to those in our
      previous study. The groups were well-matched for age (55.9+/-5.9 years), gender
      (60% women), and education (15.9+/-2.2 years), and were demographically similar
      to our previous cohort. Complex figure test recall was lower in e3/4
      heterozygotes than noncarriers, but there was no significant difference between
      e4/4 homozygotes and noncarriers. There were no other significant differences in
      mean test scores between groups, but Wechsler adult intelligence scale-revised
      (WAIS-R) digit span showed a significant negative correlation with age in the
      e4/4 homozygote group relative to e4 noncarriers (p=0.008) as we had found in our
      previous study. In conclusion, we found a significant negative correlation of
      WAIS-R digit span with age in apoE-e4/4 homozygotes relative to e4 noncarriers in
      two separate cohorts, possibly reflecting an age-related effect on frontal lobe
      function in this genetic subgroup.

PMID- 11535239
TI  - Inflammation and atrophy in multiple sclerosis: MRI associations with disease
      course.
AB  - Brain atrophy may be a useful surrogate marker of axonal loss and disease
      progression in multiple sclerosis (MS). Several studies have suggested that
      inflammatory disease activity is a risk factor for atrophy in the early stages of
      the disease, but may become less important later in the disease course. We aimed
      to investigate the relationships between atrophy and active inflammation at
      different stages of the disease course using brain volume measurements from
      magnetic resonance imaging (MRI) in patients with both relapsing-remitting (RR)
      (n=95) and secondary progressive (SP) (n=76) MS. Conventional dual echo and three
      dimensional magnetization-prepared rapid-acquisition gradient echo imaging were
      performed in all patients and in 31 healthy controls. Supratentorial and
      infratentorial brain, and lateral ventricular volumes were determined using
      modern design stereology. Patients with SP MS had smaller supratentorial
      (p=0.003) and infratentorial brain volumes (p=0.0003), and larger lateral
      ventricles (p=0.02) than patients with RR MS. RR MS patients with T(1)-enhancing
      lesions had smaller supratentorial (p=0.02) and infratentorial (p=0.002) brain
      volumes and larger ventricles (p=0.002) than those without enhancing lesions. SP
      MS patients with enhancing lesions also had significantly larger lateral
      ventricles (p=0.03). Categorical analysis showed that more RR MS patients with
      enhancing lesions had smaller supratentorial brain (p=0.005), or larger lateral
      ventricular (p=0.028) volumes, and more SP MS patients with enhancing lesions had
      increased lateral ventricle volumes (p=0.013), than patients without
      enhancements. The number of enhancing lesions was significantly correlated with
      lateral ventricular volumes in both RR MS (r=0.39, p=0.0001) and SP MS (r=0.46,
      p<0.0001). Our data shows that the presence of active inflammation on a single
      MRI in the course of RR and SP MS, is associated with a higher risk and higher
      level of brain atrophy. These findings emphasise the important long-term
      relationship between inflammation and atrophy in MS and provide additional
      support for the strategy of early anti-inflammatory treatment to protect tissue
      integrity.

PMID- 11535240
TI  - Transient hyperglycemia in ischemic stroke patients.
AB  - The aim of the study was to investigate glucose derangement and its short- and
      long-term prognostic significance in nondiabetic ischemic stroke patients. The
      study involved 262 consecutive patients, mean age: 70.1+/-12.4 years, with a
      supratentorial ischemic stroke. The following data were collected: patients
      characteristics, risk factors, comorbidities, and stroke severity assessed by the
      Scandinavian Stroke Scale (SSS). Serum glucose levels were measured on admission,
      on the next, 2nd, 3rd, 5th, 7th and 14th day after stroke onset. The outcome
      measures on day 30 were mortality and capacity to perform daily activities: the
      Barthel Index and Rankin Scale. The 1-year survival was estimated by the Kaplan
      Meier method. Cox proportional hazards regression was used to assess predictors
      of 1-year mortality in nondiabetics. Diabetes mellitus was found in 24.8% of
      patients and transient hyperglycemia in 36.3% of patients. Patients with
      transient hyperglycemia scored lower on SSS in the subsequent days of assessment
      than patients with either diabetes mellitus or normoglycemia. They had larger
      ischemic lesions on computer tomography (CT) than diabetics and had higher 30-day
      mortality than normoglycemics (p<0.05). One-year mortality was similar in
      transient hyperglycemics and diabetics, and both were significantly higher than
      in normoglycemics (p<0.05). A proportional hazards model analysis showed that
      transient hyperglycemia is not an independent predictor of death within a year
      after stroke.

PMID- 11535241
TI  - A polymorphic variation of serine to tyrosine at codon 18 in the ubiquitin C
      terminal hydrolase-L1 gene is associated with a reduced risk of sporadic
      Parkinson's disease in a Japanese population.
AB  - Recent studies suggest that ubiquitin C-terminal hydrolase-L1 (UCH-L1), a
      neuronal deubiquitinating enzyme, represents a candidate gene responsible for
      either the development of familial Parkinson's disease (PD) or the protection
      against sporadic PD in Caucasian populations, although these findings are not
      fully verified in non-Caucasian populations. To determine an association of the
      variations in the UCH-L1 gene with development of sporadic PD in a Japanese
      population, a Ser18Tyr polymorphism and an Ile93Met mutation were studied by PCR
      RFLP analysis in 74 Japanese patients with sporadic PD and 155 age-matched non-PD
      controls. The frequency of 18Tyr allele was significantly lower in PD patients
      than the controls (38.5% vs. 53.5%) (chi(2)=9.064, p=0.0026; the odds ratio=1.84,
      95% confident interval=1.23-2.74). Furthermore, the frequency of 18Tyr/Tyr
      homozygotes was significantly lower in PD patients than the controls (14.9% vs.
      33.5%), compared with that of two other genotypes combined (chi(2)=8.767,
      p=0.0031; the odds ratio=0.35, 95% confident interval=0.27-0.45). The Ile93Met
      substitution was not detected in any Japanese subjects examined. These results
      indicate that the presence of 18Tyr allele and 18Tyr/Tyr homozygosity in the UCH
      L1 gene is associated with a reduced risk for development of sporadic PD in a
      Japanese population, supporting the previous observations on sporadic PD in
      Caucasian populations.

PMID- 11535242
TI  - Genetic susceptibility to environmental toxicants. Proceedings of the
      International EEMS-ECETOC Symposium. Budapest, Hungary. 24 August 2000.

PMID- 11535243
TI  - The role of human glutathione S-transferases (hGSTs) in the detoxification of the
      food-derived carcinogen metabolite N-acetoxy-PhIP, and the effect of a
      polymorphism in hGSTA1 on colorectal cancer risk.
AB  - Food-derived heterocyclic amines (HCAs), particularly 2-amino-1-methyl-6
      phenylimidazo[4,5-b]pyridine (PhIP), are implicated in the etiology of human
      colorectal cancer (CRC) via a process of N-oxidation followed by O-acetylation or
      O-sulfation to form electrophilic metabolites that react with DNA. Glutathione S
      transferases (GSTs) detoxify activated carcinogen metabolites by catalysis of
      their reaction with GSH. However, among HCAs, only N-acetoxy-PhIP has been shown
      to be a substrate for the GSTs. By using a competitive DNA-binding assay, we
      confirm that hGSTA1-1 is an efficient catalyst of the detoxification of N-acetoxy
      PhIP. Further, we show that hGSTs A2-2, P1-1, M1-1, T1-1 and T2-2 appear to have
      low activity towards N-acetoxy-PhIP, and that hGSTs A4-4, M2-2, M4-4 and Z1-1
      appear to have no activity towards N-acetoxy-PhIP. A genetic polymorphism in the
      5'-regulatory sequence of hGSTA1 has been shown to correlate with the relative
      and absolute levels of expression of GSTA1/GSTA2 in human liver. Examination of
      hGSTA1 allele frequency in 100 Caucasian CRC patients and 226 Caucasian controls
      demonstrated a significant over-representation of the homozygous hGSTA1*B
      genotype among cases compared to controls (24.0 and 13.7%, respectively, P=0.04).
      This corresponds to an odds ratio for risk of CRC of 2.0 (95% CI 1.0-3.7) when
      comparing homozygous hGSTA1*B individuals with all other genotypes. Thus,
      individuals who are homozygous hGSTA1*B, and who would be predicted to have the
      lowest levels of hGSTA1 expression in their livers, appear to be at risk of
      developing CRC, possibly as a result of inefficient hepatic detoxification of N
      acetoxy-PhIP.

PMID- 11535244
TI  - Genetic susceptibility to adverse effects of drugs and environmental toxicants.
      The role of the CYP family of enzymes.
AB  - The majority of cytochrome P450 (CYP)-dependent xenobiotic metabolism is carried
      out by polymorphic and inducible enzymes which can cause abolished,
      quantitatively or qualitatively altered or enhanced drug metabolism. Stable
      duplication, multi-duplication or amplification of active genes, most likely in
      response to dietary components causing a selection of alleles with multiple
      genes, has been described. Several examples exist where subjects carrying certain
      alleles suffer from a lack of drug efficacy due to ultra-rapid metabolism caused
      by multiple genes or by induction of gene expression or, alternatively, adverse
      effects from the drug treatment due to the presence of defective alleles. The
      polymorphism of CYP enzymes is expected to influence the individual sensitivity
      and toxicity for different environmental agents, although there is no real
      consensus in the literature about specific firm relationships in this regard.
      Dosage requirements for several commonly used drugs that have a narrow
      therapeutic range can differ more than 20-fold dependent on the genotype or the
      enzyme expression status. The incidence of serious and fatal adverse drug
      reactions has been found to be very high among hospitalised patients and causes
      over 100,000 deaths per year in the US, making it between the 4th and 6th leading
      cause of death. It is likely that predictive genotyping could avoid 10-20% of
      these deaths. In the present contribution, an overview is presented about our
      present knowledge about the polymorphism of xenobiotic metabolising CYPs and the
      importance for adverse effects of drugs and metabolic activation of xenobiotics.

PMID- 11535245
TI  - Glutathione-S-transferase family of enzymes.
AB  - The loci encoding the glutathione-S-transferase (GST) enzymes comprise a large
      supergene family located on at least seven chromosomes. The function of the GST
      enzymes has traditionally been considered to be the detoxication of electrophiles
      by glutathione conjugation. A wide variety of endogenous (e.g. by-products of
      reactive oxygen species activity) and exogenous (e.g. polycyclic aromatic
      hydrocarbons) electrophilic substrates have been identified. Interestingly,
      recent data has suggested a role, at least for the pi class gene product, in jun
      kinase inhibition. Since many GST genes are polymorphic, there has been
      considerable interest in determining whether particular allelic variants are
      associated with altered risk (or outcome) of a variety of diseases. We describe
      recent studies in patients with asthma and cutaneous basal cell carcinoma that
      demonstrate associations between GSTP1 and GSTT1 genotypes and disease
      phenotypes. Thus, GSTP1val(105)/val(105) was protective against asthma symptoms
      and GSTT1 null was associated with a subgroup of basal cell carcinoma patients
      who develop large numbers of primary tumours in clusters. Importantly, these
      associations were characterised by relatively large odds ratios (0.11 and 7.4,
      respectively) implying that the allelic variants exert a substantial biological
      effect. These and other data indicate the importance of GST polymorphism in
      determining disease phenotype.

PMID- 11535246
TI  - Human cytosolic sulphotransferases: genetics, characteristics, toxicological
      aspects.
AB  - Cytosolic sulphotransferases transfer the sulpho moiety from the cofactor 5'
      phosphoadenosine-3'-phosphosulphate (PAPS) to nucleophilic groups of xenobiotics
      and small endogenous compounds (such as hormones and neurotransmitters). This
      reaction often leads to products that can be excreted readily. However, other
      sulpho conjugates are strong electrophiles and may covalently bind with DNA and
      proteins. All known cytosolic sulphotransferases are members of an enzyme/gene
      superfamily termed SULT. In humans, 10 SULT genes are known. One of these genes
      encodes two different enzyme forms due to the use of alternative first exons.
      Different SULT forms substantially differ in their substrate specificity and
      tissue distribution. Genetic polymorphisms have been described for three human
      SULTs. Several allelic variants differ in functional properties, including the
      activation of promutagens. Only initial results are available from the analysis
      of SULT allele frequencies in different population groups, e.g. subjects
      suffering from specific diseases and corresponding controls.

PMID- 11535247
TI  - Influence of polymorphisms of the human glutathione transferases and cytochrome
      P450 2E1 enzyme on the metabolism and toxicity of ethylene oxide and
      acrylonitrile.
AB  - A cohort of 59 persons with industrial handling of low levels of acrylonitrile is
      being studied as part of a medical surveillance programme. Previously, an
      extended haemoglobin adduct monitoring (N-(cyanoethyl)valine and N-(hydroxyethyl)
      valine) was performed regarding the glutathione transferases hGSTM1 and hGSTT1
      polymorphisms but no influence of hGSTM1 or hGSTT1 polymorphisms on specific
      adduct levels was found. A compilation of case reports of human accidental
      poisonings had pointed to significant individual differences in human
      acrylonitrile metabolism and toxicity. Therefore, a re-evaluation of the
      industrial cohort included known polymorphisms of the glutathione transferases
      hGSTM3 and hGSTP1 as well as of the cytochrome P450 CYP2E1. A detailed
      statistical analysis revealed that exposed carriers of the allelic variants of
      hGSTP1, hGSTP1*B/hGSTP1*C, characterized by a single nucleotide polymorphism at
      nucleotide 313 which results in a change from Ile to Val at codon 104, had higher
      levels of the acrylonitrile-specific haemoglobin adduct N-(cyanoethyl)valine
      compared to the carriers of the codon 113 alleles hGSTP1*A and hGSTP1*D. The
      single nucleotide polymorphism at codon 113 of hGSTP1 (hGSTP1*A/hGSTP1*B versus
      hGSTP1*C/hGSTP1*D) did not show an effect, and also no influence was seen on
      specific haemoglobin adduct levels of the polymorphisms of hGSTM3 or CYP2E1. The
      data, therefore, point to a possible influence of a human enzyme polymorphism of
      the GSTP1 gene at codon 104 on the detoxication of acrylonitrile which calls for
      experimental toxicological investigation. The study also confirmed the impact of
      GSTT1 polymorphism on background N-(hydroxyethyl)-valine adduct levels in
      haemoglobin which are caused by endogenous ethylene oxide.

PMID- 11535248
TI  - Glutathione S-transferase polymorphisms influence the level of oxidative DNA
      damage and antioxidant protection in humans.
AB  - Glutathione S-transferase genotypes GSTT1, GSTM1, GSTP1 were characterised in 155
      middle-aged men and compared with parameters of oxidative stress at the level of
      DNA and lipids, with antioxidant enzymes, and with plasma antioxidants in smokers
      and non-smokers. Smokers had on average significantly lower levels of Vitamin C,
      beta-carotene and beta-cryptoxanthin and higher amounts of oxidised purines and
      pyrimidines in lymphocyte DNA. The GSTM1 null genotype was associated with
      elevated glutathione as well as with higher Vitamin C concentration in plasma.
      Vitamin C was higher in GSTT1+ compared with GSTT1 null--as was glucose-6
      phosphate dehydrogenase activity. The homozygous GSTP1 a/a genotype was
      associated with significantly higher levels of GST activity measured in
      lymphocytes, in comparison with the b/b genotype. Using multifactorial
      statistical analysis we found significant associations between smoking, GSTP1
      genotype, plasma Vitamin C, and purine base damage in lymphocyte DNA. The
      difference in Vitamin C plasma levels between smokers and non-smokers was seen
      only with the GSTP1 b/b genotype. This group accounted also for most of the
      increase in purine oxidation in smokers. In contrast, the link between smoking
      and oxidised pyrimidines in DNA was seen only in the GSTT1 null group. It seems
      that polymorphisms in the phase II metabolising enzyme glutathione S-transferase
      may be important determinants of commonly measured biomarkers.

PMID- 11535249
TI  - Impact of metabolic genotypes on levels of biomarkers of genotoxic exposure.
AB  - Phase I and Phase II xenobiotic-metabolising enzyme families are involved in the
      metabolic activation and detoxification of various classes of environmental
      carcinogens. Particular genetic polymorphisms of these enzymes have been shown to
      influence individual cancer risk. A brief overview is presented about recent
      research of the relationship between metabolic genotypes and internal dose,
      biologically effective dose and cytogenetic effects of complex and specific
      genotoxic exposures of human study populations, and we report our new results
      from two molecular epidemiological studies. We investigated the effects of
      multiple interactions among CYP1A1 Ile462Val, CYP1A1 MspI, CYP1B1 Leu432Val,
      CYP2C9 Arg144Cys, CYP2C9 Ile359Leu, NQO1 Pro189Ser, GSTM1 gene deletion and GSTP1
      Ile105Val genotypes on the levels of carcinogen-DNA adducts determined by (32)P
      postlabelling and PAH-DNA immunoassay in peripheral blood lymphocytes from
      workers occupationally exposed to polycyclic aromatic hydrocarbons in aluminium
      plants, and in bronchial tissue from smoking lung patients. A statistically
      significant positive linear correlation was observed between white blood cell
      aromatic DNA adduct and urinary 1-hydroxypyrene (1-OHPY) levels from potroom
      workers with GSTM1 null genotype (P=0.011). Our results suggest interactions
      between GSTM1 and GSTP1 alleles in modulation of urinary 1-OHPY levels and white
      blood cell DNA adduct levels in the PAH-exposed workers. Interactions between
      GSTM1 and GSTP1 alleles, in association with particular genotype combinations of
      CYPs, were also recognised in bronchial aromatic DNA adduct levels of smoking
      lung patients. The impact of single metabolic genotypes and their combinations on
      biomarkers of exposure was usually weak, if any, in both our studies and reports
      of the literature. The effect of special metabolic gene interactions may be
      better recognised if the compared groups of individuals are stratified for
      multiple potential modulators of the observable biomarker end-point, and/or if
      chemical structure-specific biomarker methods are applied.

PMID- 11535250
TI  - Susceptibility differences in chemical carcinogenesis linearize the dose-response
      relationship: threshold doses can be defined only for individuals.
AB  - The debate on thresholds in dose-response relationships for chemical
      carcinogenesis concentrates on the question of mechanisms of action that come
      into play only at dose levels that overwhelm compensatory control mechanism, such
      as DNA repair or regulation of cell proliferation and death. In this article,
      individual susceptibility differences are introduced. It is postulated that one
      single threshold dose cannot be defined for a heterogeneous population because
      both the background rate of carcinogenesis and specific exposure-related effects
      differ between individuals. A threshold dose can therefore be defined only on an
      individual basis and for a given organ. Expressed as a time-to-tumor, the
      threshold dose results in tumor manifestation at exactly the end of the specified
      observation period. For those individuals who do not have cancer by the end of
      this period, the dose was below their individual threshold dose, for those who do
      have cancer, the dose was above their threshold dose. Based on this concept, a
      distinction between genotoxic and non-genotoxic carcinogens is no longer
      required; both types modulate time-to-tumor. Although the present analysis does
      not allow to define a threshold dose for a population, the setting of a "limit
      value" for regulatory purposes can be considered if regulators are aware of the
      fact that this splits a population at some percentile into a group for which the
      chosen standard is protective and a group for which it might not be.
      Investigation of factors that confer particular susceptibility to individuals is
      the key to an understanding of the dose-response relationship at low dose.

PMID- 11535251
TI  - Genetic susceptibility and environmental estrogen-like compounds.
AB  - Environmental chemicals with estrogenic activities have been suggested to be able
      to interact with the endocrine system. Endogenous estrogen is synthesized in the
      ovarian theca cells of premenopausal women or in the stromal adipose cells of the
      breast of postmenopausal women and minor quantities in peripheral tissue. These
      cells, as well as breast tissue, express all the necessary enzymes for this
      synthesis, CYP17, CYP11a, CYP19, 17-beta-hydroxysteroid hydrogenase, steroid
      sulfatase as well as enzymes further hydroxylating estradiol, such as CYP1A1,
      CYP3A4, CYP1B1, catechol-o-methyltransferase (COMT). Polymorphisms in these
      enzymes may have a possible role in the link between environmental estrogens and
      hormone-like substances and the interindividual risk of breast cancer.

PMID- 11535252
TI  - Risk assessment: the importance of genetic polymorphisms in man.
AB  - Many genetic polymorphisms in metabolism enzymes are important for the risk of
      cancer as shown in a large number of case-control studies. The relative risk
      estimates have shown large variations between such population studies. However,
      in most studies the relative risk estimates are in the range of 2. Some
      polymorphisms are effect modifiers, i.e. without exposure they have no
      consequence and the effect of exposure can appear independent of the genotype.
      Genetic polymorphisms in metabolism of environmental toxicants plays a
      significant role in exposures to traffic generated air pollution in Copenhagen,
      revealing statistically significant higher levels of chromosomal aberrations in
      non-smoking bus drivers with glutathion-S-transferase M1, GSTM1 null and N
      acetyltransferase 2, NAT2 slow genotypes. Combined with cohort studies showing
      positive associations between high chromosomal levels and increased cancer risk,
      such results indicate effect modification regarding cancer risk. In risk
      assessment the safety 'factor' of 10 is generally accepted to allow for variation
      in individual susceptibility. Reviewing the literature justifies the factor of 10
      when considering single polymorphisms. However in an individual with several
      susceptible metabolism genotypes as well as other determinants of susceptibility,
      e.g. defective DNA repair, poor-nutritional state, etc. the risk may increase far
      above a safety of 10.Historically, genetic polymorphisms have been taken into
      consideration in employment and currently the application in insurance situations
      is criticised.

PMID- 11535253
TI  - Association between genetic polymorphisms and biomarkers in styrene-exposed
      workers.
AB  - A comprehensive approach to evaluate genotoxic effects induced by styrene
      exposure was employed in 44 hand-lamination workers in comparison with 18
      unexposed controls. The acquired data on single-strand breaks in DNA (SSBs),
      frequency of chromosomal aberrations and HPRT mutant frequency in peripheral
      blood lymphocytes were compared to the results on genotyping of some of the
      xenobiotic-metabolising enzymes (CYP1A1, CYP2E1, epoxide hydrolase and GSTM1,
      GSTP1 and GSTT1). Multifactorial regression analysis indicated that SSB in DNA
      were significantly associated with styrene exposure and with heterozygosity in
      CYP2E1 (5'-flanking region and intron 6; r(2)=0.614). The frequency of
      chromosomal aberrations (CA), as analysed by linear multiple regression analysis,
      significantly correlated with years of employment (P=0.004) and with combinations
      of epoxide hydrolase (EPHX) genotypes (exon 3, Tyr/His and exon 4, His/Arg),
      where individuals with low and medium activity EPHX genotypes exhibited higher
      frequencies of CA than those with high activity genotypes (P=0.044, r(2)=0.563).
      Moderately higher HPRT mutant frequencies were detected in styrene-exposed
      individuals (20.2 +/- 25.8 x 10(-6)) as compared to controls (13.3 +/- 6.3 x 10(
      6)), but this difference was not significant. ANOVA (in the whole set of data)
      revealed that mutant frequencies at the HPRT gene were significantly associated
      with years of employment (F=6.9, P=0.0001), styrene in blood (F=10.1, P=0.0001),
      and heterozygosity in CYP2E1 (intron 6; F=13.5, P=0.0008) and GSTP1 (exon 5;
      F=3.6, P=0.038). In conclusion, our present data suggest that analysed biomarkers
      of DNA damage may be modulated by polymorphic CYP2E1, EPHX and GSTP1. In our
      study, styrene-specific DNA and haemoglobin adducts are under investigation.
      Completing these data with the results of genotyping of metabolising enzymes may
      provide a useful tool for individual genotoxic risk assessment.

PMID- 11535254
TI  - Ethical implications of genetic analysis of individual susceptibility to
      diseases.
AB  - Ethics can be regarded as a reflection or reconsideration of existing moral codes
      in the search of good and goes beyond moral conduct. This means that ethics is a
      never-ending process, which in science must develop with the development of
      science itself. Thus, the process of seeking better ethics is as integral within
      science as the development of new methods. Along these lines of thought it can be
      argued that (1) poor science cannot be ethically sound, (2) every scientist has a
      personal responsibility to develop ethics in his area of expertise, (3) the
      development of solid ethical background in science requires education in ethics
      as well as in methodology and scientific thinking and (4) research ethics cannot
      develop in solitude, but needs input from other scientists, other fields
      (including philosophy) and society. Several burning questions can be identified
      within genetic analysis for individual susceptibility. These ethical aspects can
      be viewed from three different perspectives: practice of research,
      patient/research subject personally and long-term implications in society. This
      paper tries more to awaken thoughts than give clear answers.

PMID- 11535255
TI  - Concluding remarks: symposium on Genetic Susceptibility to Environmental
      Toxicants.
AB  - The symposium on "Genetic Susceptibility to Environmental Toxicants" provided a
      state-of-the-art forum on the role of genetic susceptibility involving exposures
      to occupational, dietary, and other environmental toxicants. While much of the
      work focused on single gene-environmental interactions, there was a clear
      understanding that multiple gene polymorphisms in a metabolic pathway would prove
      to be essential knowledge in better assessing health risks. A clear need to
      couple these advances with better measures of exposure was also appreciated,
      along with improved methods to conduct individual risk assessment procedures. The
      ethics of these new paradigms was also discussed.

PMID- 11535256
TI  - Genetic and environmental modulation of chronic obstructive pulmonary disease.
AB  - Chronic Obstructive Pulmonary Disease (COPD) is a leading cause of morbidity and
      mortality throughout a large part of the western world. Although personal tobacco
      use has been implicated in a large number of these cases, it is also true that
      only a fraction of smokers ever develop respiratory problems. Therefore, the
      question of host susceptibility and other environmental factors should be
      considered. This paper will briefly review evidence for host susceptibility to
      COPD, review evidence for additional environmental risk factors for the
      development of COPD, and give an example of environmental interactions with a
      known genetic risk factor that further increase the risk of COPD.

PMID- 11535257
TI  - Relationship between pancreatitis and lung diseases.
AB  - Patients with acute pancreatitis may develop acute lung injury, manifest
      clinically as the adult respiratory distress syndrome. Most patients who die
      during the early stages of severe acute pancreatitis die either with or as a
      result of this lung injury. To explore the events which couple acute pancreatitis
      to lung injury, a number of recent studies have been performed in the author's
      laboratory using a variety of experimental models and interventions including
      gene-targeted deletion of chemokines, cytokines, specific receptors, and adhesion
      molecules. These studies have indicated that adhesion molecules such as
      intracellular adhesion molecule-1 (ICAM-1), neutrophils, platelet activating
      factor (PAF), substance P, and chemokines acting via the CCR-1 chemokine receptor
      play a pro-inflammatory role while complement factor C5a plays an anti
      inflammatory role in pancreatitis and lung injury. Future studies will build on
      these observations to expand the list of pro- and anti-inflammatory coupling
      factors and explore the mechanisms by which they act to cause or prevent lung
      injury in acute pancreatitis.

PMID- 11535258
TI  - Regulation of experimental lung inflammation.
AB  - Acute lung inflammation is an important component of a number of pulmonary
      diseases, including acute respiratory distress syndrome (ARDS). Much has been
      learned about the manner in which various insults to lung, such as infection or
      trauma, bring about recruitment of neutrophils into alveoli and small airways,
      resulting in parenchymal damage and organ dysfunction. In this brief review, we
      discuss the endogenous mechanisms in which the lung regulates the acute
      inflammatory response in rats to intrapulmonary deposition of IgG immune
      complexes. Emphasis is given to the participation of the transcription factor, NF
      kappaB, in the development of lung injury and the endogenous mediators which
      attempt to control the extent of lung inflammation by modulating the activation
      of NF-kappaB.

PMID- 11535259
TI  - The role of immunity in susceptibility to respiratory infection in the aging
      lung.
AB  - Respiratory tract infections, particularly pneumonia, are a leading cause of
      death in persons 65 years or older in both developed and developing countries.
      Because many attributes of immunity wane with advancing age, the elderly may be
      more susceptible to respiratory infections, even if they appear to be in good
      health. A decline in the ability of lymphoid tissues to mount an antigen-specific
      response (adaptive immunity) to specific microorganisms such as influenza virus
      or Streptococcus pneumoniae is thought to be an important factor in increasing
      susceptibility to respiratory tract infection with advancing age. However,
      abnormalities in innate immunity may also contribute to increased susceptibility
      to respiratory infections and have been poorly characterized in the elderly.
      Although changes in immune parameters such as T cell subsets and immunoglobulin
      concentrations have been observed in respiratory secretions from older healthy
      individuals compared to younger subjects, the significance of these changes for
      protective immunity in the lung is unknown. The incidence of pneumonia may be
      lessened by measures such as optimizing treatment of comorbid conditions,
      optimizing nutrition, and addressing swallowing disorders. The use of vaccines
      directed against the influenza virus and S. pneumoniae appears to have made an
      impact on the degree of morbidity and mortality, and perhaps, the incidence, of
      community-acquired pneumonia. However, better stimulation of specific immune
      responses with improved vaccines and more widespread use of these vaccines for
      protection of elderly individuals are needed.

PMID- 11535260
TI  - Deposition and clearance: unique problems in the proximal airways and oral cavity
      in the young and elderly.
AB  - Prospective longitudinal studies measuring aerosol behavior in the respiratory
      tract as humans age have not been performed. The present paper reviews
      observations related to aging of the respiratory tract and other effects more
      likely due primarily to disease and iatrogenic causes. Upper airway deposition
      was found to approximate 50% in children during inhalation of drugs thought to be
      designed primarily for deposition in the lower respiratory tract. In older
      subjects, aging per se did not have a major impact on the deposition of aerosols.
      Disease processes that develop with age were shown to be the primary cause of
      deposition abnormalities. Flow-limitation in central airways was proposed as a
      major factor responsible for central airway deposition as well as abnormal
      clearance in common obstructive lung diseases. The oral cavity, a source of
      pathogenic organisms causing pneumonia, was also studied in the elderly. Salivary
      clearance, often abnormal in the aged, was related to colonization with
      pathogenic bacteria. Salivary clearance was not obviously reduced by aging per se
      but by iatrogenic sources such as drug therapy for other diseases.

PMID- 11535261
TI  - Environmental tobacco smoke as a risk factor for respiratory disease in children.
AB  - Respiratory diseases are a frequent reason for using health care. In 1995-1996,
      diseases of the respiratory tract (ICD 460-519) contributed seven of the top 15
      reasons for visits to physician offices among children under 15 years of age in
      the United States. Environmental tobacco smoke (ETS) is a wide-spread
      environmental pollutant that has been long linked with respiratory problems. This
      paper will review the available literature on the role ETS plays in respiratory
      diseases, including asthma. This review focuses not only on the respiratory
      problems caused by ETS, but also examines the influence of age at exposure on the
      consequences of ETS and the importance of the differing sources of ETS exposure.
      As ETS is a completely preventable form of environmental pollution, the success
      or failure of various types of interventions will also be reviewed.

PMID- 11535262
TI  - Inhaled endotoxin, a risk for airway disease in some people.
AB  - Despite the tremendous inter-individual variability in the response to inhaled
      toxins, we simply do not understand why certain people develop disease when
      challenged with environmental agents and others remain healthy. To address this
      concern, we investigated whether the toll-4 (TLR4) gene, that has been shown to
      affect lipopolysaccharide (LPS) responsiveness in mice, underlies the variability
      in airway responsiveness to inhaled LPS in humans. Here we show that common, co
      segregating missense mutations (Asp299Gly and Thr399Ile) in the extracellular
      domain of the TLR4 receptor are associated with a significantly blunted response
      to inhaled LPS in 83 humans. Transfection of THP-1 cells demonstrates that the
      Asp299Gly mutation (but not the Thr399Ile mutation) interrupts TLR4-mediated LPS
      signaling. Moreover, the wild type allele of TLR4 rescues the LPS hyporesponsive
      phenotype in either primary airway epithelial cells or alveolar macrophages
      obtained from individuals with the TLR4 mutations. Our findings provide the first
      genetic evidence that common mutations in TLR4 are associated with differences in
      LPS responsiveness in humans, and demonstrate that gene sequence changes can
      alter the ability of the host to respond to environmental stress.

PMID- 11535263
TI  - Rodent models of susceptibility: what is their place in inhalation toxicology?
AB  - There is renewed interest in inhalation toxicology regarding 'susceptibility' as
      associated with host variables, including genetics, age, diet, and disease. This
      interest derives from epidemiology that shows air pollution-related human
      mortality/morbidity, especially among individuals with cardiopulmonary disease.
      Several animal models with experimental or genetically-based cardiopulmonary
      diseases are now being incorporated into inhalation toxicology studies to
      investigate mechanisms that underlie host susceptibility. However, current models
      have strengths and limitations as to how they mimic the essential features of
      human diseases. To date, animal models of pulmonary hypertension, bronchitis,
      asthma, and cardiovascular disease, but not emphysema, appear to exhibit greater
      susceptibility to air pollution particulate matter. As in humans, host
      susceptibility appears to involve multiple genetic and environmental factors, and
      is poorly understood, but the database of information is growing rapidly. As
      existing models gain wider use, our understanding of the models will improve and
      encourage refinements/development of models that integrate both genetic and
      environmental factors to better mimic the human condition.

PMID- 11535264
TI  - Stress and influenza viral infection: modulation of proinflammatory cytokine
      responses in the lung.
AB  - Viral infection of the respiratory tract induces a complex series of cellular and
      molecular events leading to immunological responses designed to terminate viral
      replication. Anti-viral immunity involves natural resistance mechanisms that
      overlap and modulate the development of the subsequent adaptive immune responses.
      An experimental murine infection with influenza A/PR8 virus was used to examine
      the effects of stress-induced activation of the nervous and endocrine systems on
      components of innate immunity. Proinflammatory cytokine responses (IL-1alpha, IL
      6 and TNFalpha) were measured in the lungs during an influenza A/PR8 viral
      infection. For activation of the nervous and endocrine systems, restraint stress
      (RST) was applied prior to and during infection. Following infection, IL-1alpha
      increased transiently, while elevated IL-6 persisted; TNFalpha was not detected.
      RST suppressed virally-induced IL-1alpha, while IL-6 was unaffected. These data
      demonstrate differential regulation of proinflammatory cytokines by stress. The
      mechanism underlying suppression of the lung IL-1alpha in stressed mice is
      currently unknown; its downregulation may contribute to increased viral
      pathogenesis in stressed individuals.

PMID- 11535265
TI  - Clinical and cellular effects of cytochrome P-450 modulators.
AB  - Stress stimulates the hypothalamic-pituitary-adrenal axis and leads to elevated
      glucocorticoid hormones (GCs). GCs reduce inflammation and suppress responses
      mediated by cytokines, including fever and pulmonary inflammation. Besides
      cyclooxygenases and lipoxygenases, cytochrome P-450 enzymes (CYP), referred to as
      epoxygenases, are also involved in the metabolism of arachidonic acid,
      implicating epoxygenases in regulating inflammation and the generation of fever.
      Intraperitoneal injection of lipopolysaccharide (LPS) triggers fever in rats and
      mice, and administration of compounds known to induce CYP reduces LPS-induced
      fever, while inhibitors of CYP suppress fever. Consistent with these findings,
      inhibitors of CYP augment the elevation of LPS-induced prostaglandin E2 levels,
      an endogenous pyrogen, and administration of epoxygenase metabolites results in
      antipyresis. CYP inducers also reduce lung inflammation, the resulting mucous
      cell metaplasia, and the percentage of Bcl-2-positive mucous cells in rat airways
      after intratracheal instillation of LPS. Together, these observations indicate
      that CYP modulators may have therapeutic anti-inflammatory effects, and this
      pathway may be involved in stress-induced reduction of inflammation.

PMID- 11535266
TI  - Worksite tobacco control programs: the role of occupational health.
AB  - Worksite tobacco control initiatives face a crucial challenge: the growing
      occupational disparity in smoking prevalence. Blue-collar workers are more likely
      to be smokers than workers are in white-collar jobs. Blue-collar workers also
      experience a high prevalence of hazardous exposures on the job. Given these
      multiple risks, it is imperative that successful comprehensive programs be
      developed to promote and protect the health of blue-collar workers. Although
      evidence is still accruing about the efficacy of workplace interventions
      integrating tobacco control and occupational health, it is possible to identify
      promising intervention strategies by drawing on the preliminary evidence on
      effective worksite interventions. The effectiveness of worksite tobacco control
      interventions will be enhanced when coordinated interventions aim to promote
      cessation among individual smokers, build social support for quitting and social
      norms that support non-smoking, engage management in assuring a healthy work
      environment, involve workers' families in non-smoking initiatives, and provide
      links to community and public policy initiatives that support tobacco control as
      well as a broader effort promoting worker health.

PMID- 11535267
TI  - Susceptibility of youth to tobacco: a social ecological framework for prevention.
AB  - For most smokers, tobacco dependence begins in childhood or adolescence. This
      review summarizes the state of social science with respect to the prevention of
      tobacco use. Social ecology is introduced as a theoretical framework useful for
      organizing prevention approaches. In recent years, the field has shifted from
      approaches directed at individuals, towards appreciation of additional, more
      comprehensive social and environmental influences on initiation. These range from
      intra-individual factors (including physiological responses to nicotine and the
      psychology of use) to individual, interpersonal, organizational, community, and
      population factors affecting access and demand. This review highlights prevention
      approaches that address social and societal influences, from school programs that
      attempt to change susceptibility of individual youth to tobacco, to community
      projects, media campaigns, restrictive policies, and tobacco pricing. The most
      promising approaches are those designed with input based on extensive formative
      research including studies with youth, directed at multiple levels of the social
      ecology, and sustained over time with significant resources and ongoing, multi
      sector inputs.

PMID- 11535268
TI  - Methods for modeling particle deposition as a function of age.
AB  - The purpose of this paper is to review the application of mathematical models of
      inhaled particle deposition to people of various ages. The basic considerations
      of aerosol physics, biological characteristics and model structure are presented
      along with limitations inherent in modern modeling techniques. Application of the
      models to children and senescent adults has been largely based on extrapolating
      anatomical and physiological data from young adults to match the changes observed
      during growth and aging. Sample results are included for total particle
      deposition and deposition in the bronchial and pulmonary regions. The models
      proposed provide particle deposition predictions that are consistent with the
      scant measurements available. The models discussed appear to be on firm
      theoretical grounds, but they are largely limited in application to simple
      aerosols and average individuals. Also, additional validation of the
      computational predictions is needed.

PMID- 11535276
TI  - Irish soil and land-use classifications as predictors of numbers of badgers and
      badger setts.
AB  - This study investigated possible associations between soil types, land use and
      badger numbers in an area of the Irish Midlands where badger removal had been
      conducted during 1989-1994. For this purpose, the area was divided into
      approximately 2500 geo-referenced square grids of 0.5 degrees km per side. For
      the outcomes (setts per grid, badgers per grid and tuberculous badgers per grid),
      Poisson models of land use, of soil type, and a combination of these two were
      developed. Influential grids were removed and the models adjusted for over
      dispersion in the badger outcomes. Mineral-based soils, dry and very-dry peat
      soils supported increased numbers of setts and badgers. High-quality pasture was
      the major land use (pastures often are found on mineral-based soils) and
      supported increased numbers of setts, badgers, and tuberculous badgers. "Natural"
      areas also supported more setts and broad-leaf forested areas were associated
      with increased tuberculous badger numbers. Discontinuous urban areas tended to
      decrease sett numbers per grid. Hedgerow length was not an important predictor
      given the information on soil type and land use. Spatial correlations existed for
      badger setts in 1 degrees km grids, for badger numbers in 1.5 degrees km grids,
      and for tuberculous badgers in 2 degrees km grids. The latter two grids have
      approximately the same area as the territory size used by a social group of
      badgers. There were no spatial correlations at the smallest (0.5 km) grid size.

PMID- 11535277
TI  - The impact of Theileria parva infections and other factors on calf mean daily
      weight gains in smallholder dairy farms in Murang'a District, Kenya.
AB  - The association between mean daily weight gain, Theileria parva infections,
      clinical East Coast fever and other possible determinants of weight gain were
      examined in a longitudinal observational study that was conducted in cohorts of
      female calves from five agro-ecological zone (AEZ)-grazing strata. The strata
      were upper-midlands (UM) 1 zero-grazing, UM 1 open-grazing, UM 2 zero-grazing, UM
      4 zero-grazing and UM 4 open-grazing. In total, 225 calves on 188 smallholder
      dairy farms were visited within the first 2 weeks of life and thereafter at
      biweekly intervals up to the age of 6 months between March 1995 and August 1996.
      During each visit, the calves were weighed and other calf-management practices in
      the farm during the visit such as housing, feeding and tick control also were
      recorded. Other events such as morbidity and mortality between or during the
      visits were also recorded. The overall mean daily weight gains were 0.24-0.29 kg
      (S.D.=0.17-0.22 kg) and were lower than the recommended targets for smallholder
      farms of 0.40-0.50 kg. The major tendency in variability of daily weight gains
      was due to visit-to-visit variation (especially in calves >3 months old).
      Differences in mean daily gains were associated with AEZ-grazing strata and calf
      level factors that included breed of calf, calf sickness, incidence of ECF,
      feeding of milk, concentrate feeds and minerals and interaction between calf age
      and AEZ-grazing strata (P<0.05). ECF and other calf sicknesses exerted a temporal
      effect on calf-growth at the height of illness and immediately after; calves
      later recovered the lost growth except where other factors such as poor calf
      nutrition prevailed. Improvement in calf-growth in Murang'a District is
      achievable and extension services should continue to target individual-calf-level
      management practices.

PMID- 11535278
TI  - Participatory diagnosis of a chronic wasting disease in cattle in southern Sudan.
AB  - In southern Sudan, livestock keepers identified a chronic wasting disease in
      adult cattle as one of their most-serious animal-health problems. Participatory
      appraisal (PA) methods and conventional veterinary-investigation methods were
      used to characterise the chronic wasting disease and identify linkages between
      indigenous knowledge and modern veterinary knowledge. The local characterisation
      of chronic wasting encompassed trypanosomosis, fasciolosis, parasitic
      gastroenteritis and schistosomosis (as both single and mixed infections).A
      standardised PA method called matrix scoring had good reproducibility when
      investigating local perceptions of disease-signs and disease causes. Comparison
      of matrix-scoring results showed much overlap with modern veterinary descriptions
      of cattle diseases and the results of conventional veterinary investigation.
      Applications of PA methods in remote areas with very limited veterinary
      infrastructure are discussed. The validation of data derived from PA is discussed
      by reference to the low sensitivity of 'field-friendly' diagnostic tests for
      important cattle diseases.

PMID- 11535279
TI  - A case-control study on scrapie in Norwegian sheep flocks.
AB  - Scrapie first was detected in indigenous sheep in Norway in 1981, and from 1995
      to 1997 an increase in the number of flocks with scrapie cases was recorded.
      These flocks were mainly in one geographical region. A study to identify risk
      factors for scrapie was conducted. The study had three frequency-matched controls
      selected for every case within the same Veterinary District. A questionnaire was
      submitted to 176 sheep flocks (42 had been scrapie flocks). The data obtained by
      the questionnaire were linked to data collected from governmental and industry
      registers. After imputing missing data using single random imputation, the
      statistical analysis was performed using multivariable conditional logistic
      regression. Purchase of female sheep from scrapie flocks, sharing of rams, or
      sharing of pastures between different flocks were the risk factors associated
      with the occurrence of scrapie. Of factors potentially sustaining and promoting
      the infection in the flock, number of winter-fed sheep, number of buildings for
      housing sheep, rams and ewes shared room during mating period and increase in the
      flock size were associated with scrapie. We interpret these findings to show that
      factors involving transfer of sheep between flocks or direct contact between
      sheep of different flocks are important for the spread of scrapie. Management
      factors are important for the development of scrapie. However, it was not
      possible to discriminate between the different management factors in this study
      at the flock level. Also, factors indicating awareness and interest of the farmer
      (as well as willingness to contact a veterinarian for diseased sheep) were
      related to the detection of scrapie in the flock.

PMID- 11535280
TI  - Validation of a test for dams carrying foetuses persistently infected with bovine
      viral-diarrhoea virus based on determination of antibody levels in late
      pregnancy.
AB  - Our objective was to estimate, using a generalised linear mixed-model approach,
      the sensitivity and specificity of an indirect ELISA when used to identify dams
      pregnant with persistently bovine viral-diarrhoea virus (BVDV)-infected foetuses.
      Cows that had been tested for antibodies to BVDV with a positive result during
      their pregnancy and where the offspring had been tested for both antibody and
      virus were identified by accessing the Swedish BVD database and the official
      pedigree records. The resulting data set consisted of 2162 cow-calf pairs in 126
      herds, of which 281 included virus-positive calves. The sensitivities and
      specificities at 12 different decision thresholds (corresponding to optical
      densities (ODs) between 0.5 and 1.6) were estimated using generalised linear
      mixed models (binomial error, logit link), in which the gold standard (the BVDV
      status of the calf) was included as a covariate. In each model, the dependent
      variable was the dichotomous test result at the decision threshold in question.
      There was a significant positive interaction between the calf's status and
      gestational stage in all 12 models--indicating that the sensitivity and
      specificity at any given decision threshold was improved when the the test was
      performed later in pregnancy. The test should be applied only when samples have
      been taken in late gestation--not before the seventh month in pregnancy. If
      applied during the last months of pregnancy, the point estimate of the
      sensitivity ranges between 0.94 and 1.0 as the decision threshold is moved from
      1.0 and downwards to 0.7. Similarly, the specificity ranges between 0.39 and 0.67
      as the decision threshold is moved from 0.8 and upwards to 1.1.

PMID- 11535281
TI  - Evaluation of official eradication-campaigns data for investigating small
      ruminant brucellosis in the province of Leon, Spain.
AB  - Brucellosis official eradication-campaigns data were used to study the
      epidemiology of the small-ruminant brucellosis infection in the province of Leon
      (northwest Spain). Data from three consecutive campaigns (1997-1999) were
      retrieved from flock sheets from controlled flocks and from other official
      statistics. In general, flock information was scarce, with a small percentage of
      contradictory data and other deficiencies that might have affected the campaign
      results. Nevertheless, unconditional multivariable logistic regression showed
      four risk factors for brucellosis infection in 1999: larger flock size, higher
      percentage of flocks in the town that are seropositive and having been
      brucellosis positive in 1997 and 1998. Despite of the scarcity of data available
      from official records, they were useful to explain, in part, the extent of the
      SRB in the province of Leon in 1999.

PMID- 11535282
TI  - Estimation of sensitivity, specificity and predictive values of two serologic
      tests for the detection of antibodies against Actinobacillus pleuropneumoniae
      serotype 2 in the absence of a reference test (gold standard).
AB  - Latent-class models were used to determine the sensitivity, specificity and
      predictive values of a polyclonal blocking enzyme-linked immunosorbent assay
      (ELISA) and a modified complement-fixation test (CFT) when there was no reference
      test. The tests were used for detection of antibodies against Actinobacillus
      pleuropneumoniae serotype 2 in a survey of respiratory diseases in Danish
      finishing pigs. The estimates were obtained by maximum-likelihood and also by a
      Bayesian method (implemented with Gibbs sampling). Possible dependence of
      diagnostic errors was investigated by comparing models where independence was
      assumed to models allowing for conditional dependence, given the true disease
      status. No strong evidence of conditional dependence in either test sensitivity
      or specificity was found. Assuming independence, maximum-likelihood estimates and
      95% confidence intervals of the sensitivity and specificity of the ELISA were
      100% and 92.8% (90.1-95.5%) and the corresponding values of the CFT were 90.6%
      (85.8-95.4%) and 98.6% (98.0-99.3%), respectively. Bayesian estimates and
      posterior 95% credible intervals of the sensitivity and specificity of the ELISA
      were 99.7% (98.7-100%) and 92.7% (89.9-95.3%) and of the CFT were 90.6% (86.0
      95.3%) and 98.7% (98.0-99.3%). The sensitivity and specificity of a combined
      test, where the CFT is subsequently applied to the pig sera that test positive in
      the ELISA, were estimated at 90.2% (85.6-95.0%) and 99.9% (99.8-100%),
      respectively. The cost of the combined test was less than the cost of the use of
      the CFT alone, at prevalences <54%. Prevalences and predictive values and their
      95% limits were estimated in six sub-samples of data. The estimates of
      sensitivity and specificity obtained in the present investigation generally
      validate those reported from other sources.

PMID- 11535283
TI  - Establishment and maintenance of a longitudinal study of bovine spongiform
      encephalopathy (the ULiSES scheme).
AB  - This paper addresses the issues of tracing and compliance encountered in setting
      up and maintaining a UK-wide 5-year observational study of beef cattle. The 5
      year prospective study was initiated in 1997 to investigate the occurrence of
      bovine spongiform encephalopathy (BSE) in a single herd of pedigree Aberdeen
      Angus cattle, in which BSE had been detected at low prevalence. The study was
      given the acronym ULiSES (University of Liverpool Spongiform Encephalopathy
      Scheme). All cattle present on the farm at the start of the scheme were
      registered as members of the study population (n=320), as were all calves
      subsequently born on the farm (n=350). Animals that were sold (n=291) were traced
      and monitored at destination farms. Farmers were requested to give advance
      notification of slaughter of any ULiSES animal and an attempt was made to collect
      post-mortem samples of nervous tissue, peripheral lymphoid tissue and striated
      muscle from all animals in the scheme at the time of slaughter, death or
      euthanasia. Sections of medulla were examined (by standard histopathological
      techniques) for the presence of spongiform change. Remaining samples were stored
      at -70 degrees C for future investigation by alternative tests. At the halfway
      point of the scheme in October 1999, 75.2% (506/673) of the study population was
      still alive; 42% (284) of the population was still alive on the study farm and
      33% (222) was distributed on other farms throughout the UK. Complete sets of
      specimens had been recovered from 77% (129/167) of dead animals. All brainstem
      sections were negative by histopathological examination. No suspect cases of BSE
      were reported in ULiSES animals. Failure to recover specimens occurred
      principally in animals which had left the study farm. The main cause of specimen
      loss was a failure of compliance in a small number of individuals who had
      purchased large numbers of ULiSES animals, and subsequently slaughtered them
      without contacting the University. Despite this, farmer compliance was generally
      high. The ULiSES scheme shows the feasibility of a country-wide longitudinal
      observational study spanning a period of several years and indicates the large
      impact of small numbers of non-compliant individuals.

PMID- 11535284
TI  - The effect of an outbreak of respiratory disease on herd-level milk production of
      Norwegian dairy farms.
AB  - This study was done to evaluate the effect of an outbreak of acute respiratory
      disease associated with bovine respiratory syncytial virus (BRSV) on the daily
      milk yield per cow in Norwegian dairy-cattle farms. Retrospective data from 184
      dairy herds located in two neighbouring veterinary districts during the study
      period (December 1994-May 1995, during which an epidemic of acute respiratory
      disease associated with BRSV occurred in this area) were analysed. Data on the
      bulk-milk deliveries and the date of the outbreak were collected at herd level,
      whereas information on calving dates and parity was collected at cow-level. The
      effect of the herd outbreaks on the daily milk yield was analysed with a repeated
      measurement approach. The average daily milk loss was estimated to be 0.70kg per
      cow for 7 days after a herd outbreak (compared with the period >1 week prior to
      an outbreak), adjusted for the herd-level lactation stage, parity and their
      interaction term. We consider the estimated milk loss associated with a herd
      outbreak of epidemic respiratory disease to be of minor importance.

PMID- 11535285
TI  - A stochastic model to estimate the prevalence of scrapie in Great Britain using
      the results of an abattoir-based survey.
AB  - In 1997/1998, an abattoir survey was conducted to determine the likely exposure
      of the human population to transmissible spongiform encephalopathy (TSE)
      infection in sheep submitted for slaughter in Great Britain. The survey examined
      brain material from 2809 sheep processed through British abattoirs. Sampling was
      targeted by age: 45% of animals tested were > or =15 months old. All samples of
      adequate quality (98%) were tested for signs of scrapie infection using
      histopathology and scrapie-associated fibril (SAF) detection and 500 were tested
      using immunohistochemistry (IHC). No conclusive positive animals were found using
      either histology or IHC. Ten animals were positive by SAF. Standard statistical
      analyses suggest (with 95% confidence) that the prevalence of detectable (by
      histopathology) infection in the slaughter population was < or =0.11%. However,
      the incubation period of scrapie is long (usually around 2-3 years) and none of
      the tests used in the survey is capable of detecting scrapie infection in the
      early stages of infection. We present an age-structured stochastic model
      incorporating parameters for the incubation period of scrapie, prevalence of
      infection by age and test sensitivity. Using the model, we demonstrate that the
      negative results obtained for all samples using IHC and histopathology are
      consistent with a true prevalence of infection in the slaughter population of up
      to 11%. This suggests that up to 300 of the animals tested might have been
      infected but the infection was not sufficiently advanced in these animals to be
      detectable by IHC or histopathology. The survey was designed to detect a
      prevalence of 1% with a precision of +/-0.5% and a confidence level of 95% in
      each age group assuming that diagnostic tests were 100% specific and sensitive
      from a known stage in the incubation period. The results of the model demonstrate
      that to estimate a true prevalence of scrapie infection of 1% with an accuracy of
      +/-0.5% would have required a far larger sample size. An accurate estimate of the
      required sample size is complicated by uncertainty about test sensitivity and the
      underlying infection dynamics of scrapie. A pre-requisite for any future abattoir
      survey is validation of the diagnostic tests used in relation to both stage of
      incubation and genotype. Sampling in the <15-month age group was of no value in
      this survey because the diagnostic tests used were thought to be ineffective in
      most of the animals in this age group.

PMID- 11535286
TI  - An economic model for on-farm decision support of management to prevent
      infectious disease introduction into dairy farms.
AB  - A more-closed farming system can be a good starting point for eradication of
      infectious diseases from within a herd. The economic implications of a more
      closed farming system will not always be obvious to farmers. The management
      decisions are related to different parts of the farm and are farm-specific. To
      support these decisions, a model was developed of the economic consequences of a
      more-closed system (a simple static and deterministic design was used). The risk
      factors in the model were based solely on bovine herpesvirus type 1 (BHV1) but
      losses due to introduction of BVDV, L. hardjo, and S. dublin were added to the
      model. The model was verified and partly validated and a sensitivity analysis was
      done. The cost to one 55-cow dairy farm that refrained from purchasing cattle,
      provided protective clothing to professional visitors and a temporary employee,
      and built and maintained a double fence around 6 ha of land to prevent over-the
      fence contacts was Dfl. 4495 over 5 years. The probability of disease
      introduction was decreased by 74%. The prevented losses for disease introduction
      amounted to Dfl. 7033 over 5 years (net benefits of Dfl. 2538 over 5 years).A
      more-closed system would be still beneficial when a sanitary barrier was used
      instead of just protective clothing, when the probability of introduction of
      infectious diseases was decreased, and when odds ratios in the model were
      replaced by more-conservative relative risks. The benefits became negative when a
      farm had to build and maintain a double fence around 12 ha instead of 6 ha, when
      the probability of introduction of all diseases was decreased by 50%, and when
      the estimations were based solely on BHV1.

PMID- 11535287
TI  - Application of the California mastitis test in intramammary Streptococcus
      agalactiae and Staphylococcus aureus infections of camels (Camelus dromedarius)
      in Kenya.
AB  - A study was conducted on 207 lactating camels in six herds in Kenya to evaluate
      the California mastitis test (CMT) for the detection of intramammary infections
      (IMIs) caused by Streptococcus agalactiae and Staphylococcus aureus and to
      investigate the prevalence of both the pathogens in the camel udder. IMI with S.
      agalactiae was found in 12% of all camels sampled. IMI with S. aureus was present
      in 11% of all camels sampled. The herd-level prevalence of IMI varied between 0
      and 50% for S. agalactiae and between 0 and 13% for S. aureus. Longitudinal
      observations over 10-12 months confirmed persistent infections for both
      pathogens. Observations in one herd suggested that camel pox was a contributing
      factor in spreading and exacerbating S. agalactiae udder infections.The CMT had
      quarter-level sensitivities of 77 and 68% for S. agalactiae and S. aureus in
      camels, respectively. The CMT specificities were 91% for both the pathogens.

PMID- 11535288
TI  - Parkinson disease: etiology, pathogenesis and future of gene therapy.
AB  - Parkinson disease (PD) is a progressive neurological disorder with a prevalence
      of 1-2% in people over the age of 50. It has a world-wide distribution and has no
      gender preference. The neurological hallmark of PD is the presence of Lewy bodies
      and is characterized by the degeneration of nigrostriatal dopaminergic neurons.
      The causes of PD are unknown but considerable evidence suggests a multifactorial
      etiology involving genetic and environmental factors. A molecular genetic
      approach identified three genes and at least two additional loci in rare familial
      forms of PD. Two of these genes are involved in the ubiquitin mediated pathway of
      protein degradation and the third one is a highly expressed protein in the
      synaptic terminal and is called alpha-synuclein. In animal models, it has been
      shown that use of the household pesticide which is known to contain rotenone,
      causes PD. Thus, a combined action of genetic and environmental factors is
      responsible for the pathogenesis of PD. Although use of levodopa or dopamine
      agonists can substantially reduce clinical symptoms, and transplantation of fetal
      nerve tissue still remains as an alternative therapy (although it has been
      recently shown to be having no overall benefit), directed delivery of glial cell
      derived neurotrophic factor (known to have trophic effects on dopaminergic
      neurons) may also be a beneficial therapeutic option for PD patients.

PMID- 11535289
TI  - Callosal commissural neurons of Dab1 deficient mutant mouse, yotari.
AB  - The yotari mouse is an autosomal recessive mutant mouse, caused by mutation of
      disabled homolog 1 (Dab1) gene. The mutant mouse is recognized by unstable gait
      and tremor and by early deaths around at the time of weaning. The
      cytoarchitectures of cerebeller and cerebral cortices and hippocampal formation
      of the yotari mouse are abnormal. These malformations strikingly resemble those
      of reeler mouse. In the present study we examined the callosal commissural (CC)
      neurons of yotari, reeler and normal mice with the injection of recombinant
      adenovirus into the frontal area 1 (Fr1) to find some possible phenotypes
      specific for the yotari mouse. The distribution pattern of CC neurons of the
      yotari was similar to that of the reeler: retrogradely labeled CC neurons were
      seen throughout all depths of the contralateral Fr1. However, the present
      statistical analysis revealed that the difference of the mean intracortical
      position of the CC neurons between the yotari and the reeler is significantly
      different (Student's t-test), suggesting that the phenotype of the yotari is
      clearly different from that of the reeler.

PMID- 11535290
TI  - Circadian and photic regulation of cryptochrome mRNAs in the rat pineal gland.
AB  - Expressions of Cry1 and Cry2 mRNA in the rat pineal gland were examined by
      Northern blot. The levels of Cry1 and Cry2 transcript had a marked circadian
      rhythm with peaks at circadian time (CT) 20 in constant darkness. But the
      amplitude of the Cry1 rhythm was higher than that of the Cry2 rhythm.
      Furthermore, a significant increase in Cry1 mRNA levels was caused by light pulse
      given at CT 16 but not at CT 4, but the expression of Cry2 was not significantly
      induced by light pulses given at either CT 4 or CT 16. These results suggest that
      Cry1 in the pineal gland is regulated by photic and circadian information but
      Cry2 is only regulated by circadian information.

PMID- 11535291
TI  - Neurosteroids stimulate G protein-coupled sigma receptors in mouse brain synaptic
      membrane.
AB  - Dehydroepiandrosterone, its sulfate (DHEAS) and pregnenolone sulfate,
      representative neurosteroids as well as (+)-pentazocine concentration-dependently
      stimulated the [35S]GTPgammaS binding in synaptic membranes of mouse prefrontal
      cortex. These stimulations were blocked by NE-100, a sigma-receptor antagonist,
      and by progesterone, another type of neurosteroid. The DHEAS-induced stimulation
      was blocked by the pertussis toxin (PTX)-treatment, and completely recovered by
      reconstitution of PTX-treated membranes with recombinant G(i1), but not with
      G(oA). DHEAS also stimulated the [35S]GTPgammaS binding in the coronal sections
      of mouse brain in NE-100- or progesterone-reversible manner. These findings
      suggest that some neurosteroids may act on metabotropic sigma receptors, and this
      study may be the first to show the coupling of neurosteroid binding site and
      G(i).

PMID- 11535292
TI  - Backward and forward leaning postures modelled by an fBm framework.
AB  - Body leaning effects on postural control have been assessed by recording the
      centre of pressure (CP) displacements in healthy subjects under three
      experimental conditions (REF, BWD and FWD corresponding to upright, backward
      leaning and forward leaning of the body, respectively). The CP displacements were
      used to compute the motions of the vertical projections of the centre of gravity
      (CG(v)) and those of the difference CP-CG(v). A frequential analysis shows that
      the main effect takes place on CP-CG(v) motions, suggesting increased muscular
      activity in these leaning postures. In addition, changes also occur on CG(v)
      motions, especially in the antero-posterior (AP) direction. Modelling these
      motions as fractional Brownian motion (fBm) indicates that leaning the body
      induces, in the AP direction, a shift in the time interval Deltat at which the
      corrective process takes over the initial one operating in open-loop. In FWD and
      BWD conditions, the Deltat is diminished whilst the mean distance covered at this
      Deltat is increased for both CG(v) and CP-CG(v) motions. Moreover, more
      determinism in the overall upright stance control is observed in the corrective
      (closed-loop) process involving CG(v) motions. These facts emphasize the
      inability for the CP displacements to express properly the overall body sway in
      upright stance control.

PMID- 11535293
TI  - Radial glia is a progenitor of neocortical neurons in the developing cerebral
      cortex.
AB  - Neocortical neurons are produced by cell division of neural stem cells in the
      ventricular zone of the cerebral cortex. We investigated the production of
      neurons by infecting neuroepithelial cells with a modified GFP-recombinant
      adenovirus. The adenovirus DNA is inherited by only one daughter cell at each
      cell division and travels one way from the progenitor to the progeny. Since the
      ventricular zone (VZ) of the embryo neocortex expressed an adenovirus receptor,
      CAR ubiquitously, morphology and cell-lineage of cells in the VZ could be
      revealed by the adenovirus infection. Radial glias, cells with a bipolar shape,
      and spherical cells were found as modified-GFP-positive (mGFP+) in the VZ. The
      bipolar cells (radial cells) had a radial process not in contact with the pia
      mater and a growth-cone-like structure at the edge of their radial process, while
      the radial glias had a process spanning all the cortical layers. Ten hours after
      viral infection, most mGFP+ cells were radial cells. In the following 8 h, the
      percentage of mGFP+ radial glias in mGFP+ neocortical cells increased from 18 to
      50%, while that in radial/spherical cells decreased from 75 to 19%. The radial
      glias often divided asymmetrically and produced spherical cells and neuronal
      precursors. The spherical cells seemed to become radial cells by extending a
      radial process. The spherical cells, radial cells and radial glias seemed to
      constitute a proliferating cell cycle during which postmitotic neuronal
      precursors are produced. The neuronal precursors that inherited the radial
      processes migrated radially and developed into neocortical neurons. Four days
      after the viral infection, 97% of mGFP+ cells were neocortical neurons. Here, we
      propose that the radial glia is a progenitor of neocortical neurons, and that a
      significant number of radially migrating neurons is guided by their own radial
      processes connected to the pia mater.

PMID- 11535294
TI  - Changes in jaw reflexes by stimulation of the hypothalamus in anesthetized
      rabbits.
AB  - Changes in the masseteric monosynaptic reflex (MMR) and jaw-opening reflex (JOR)
      responses resulting from conditioning stimulation in the hypothalamus were
      studied in anesthetized rabbits. Stimulation of the lateral hypothalamus evoked a
      facilitation of the MMR and an inhibitory or facilitatory effect on the JOR. The
      facilitatory effect on JOR was stronger than that on the MMR. The facilitatory
      effective site for the JOR was in the dorsal and lateral directions as compared
      to the inhibitory field. The results suggest two functionally distinct regions in
      the lateral hypothalamus that separately project to the jaw-opening muscles.

PMID- 11535295
TI  - Subcellular localization of neuronal nitric oxide synthase in the superficial
      gray layer of the rat superior colliculus.
AB  - The superficial layers of the rat superior colliculus (sSC) receive innervation
      from retina and include nitric oxide synthase (NOS)-immunoreactive neurons. We
      used electron microscopic immunocytochemistry to assess the subcellular
      localization of neuronal NOS (nNOS) in the sSC. nNOS immunoreactivity was
      detected on the external membrane of mitochondria, endoplasmic reticulum, in pre-
      and postsynaptic profiles and also diffusely distributed in the cytosol.
      Postsynaptic labeled regions were often associated with presumptive retinal
      unlabeled terminals. Microtubules also appeared intensely labeled. These results
      show that NOS immunoreactive neurons may be innervated by retinal terminals and
      suggest an association of nNOS with cytoskeletal elements.

PMID- 11535296
TI  - 5-HT acting on 5-HT(1/2) receptors does not participate in the in vitro hypoxic
      respiratory depression.
AB  - The involvement of serotoninergic mechanisms in the central respiratory
      depression produced by hypoxia was studied in the newborn rat brainstem-spinal
      cord preparation. The respiratory frequency measured by the C4 ventral root
      activity was recorded. 5-HT (30 microM) superfusion elicited a rapid increase in
      respiratory frequency, prevented by a treatment with methysergide (a 5-HT(1/2)
      receptor antagonist) (40 microM). To investigate the possible participation of 5
      HT in hypoxic respiratory depression, this concentration of methysergide was
      added to the bathing medium during hypoxia. Methysergide did not modify the
      decrease in respiratory frequency produced by hypoxia. In order to ensure that
      other 5-HT subtype receptors were not involved in hypoxic respiratory depression,
      5-HT was added to the bath during hypoxic-methysergide tests; no effect on
      respiratory frequency was observed. These results suggest that in the newborn rat
      brainstem-spinal cord preparation, serotoninergic mechanisms are not involved in
      the elaboration of the in vitro respiratory response to hypoxia.

PMID- 11535297
TI  - Increase in number of functional release sites by cyclic AMP-dependent protein
      kinase in cultured neurons isolated from hippocampal dentate gyrus.
AB  - The enhancement of synaptic exocytosis is one form of long-term potentiation
      (LTP) of synaptic transmission. As possible mechanisms underlying this
      enhancement, increases in the release probability and/or the number of release
      sites are suggested. To obtain direct evidence for the increase in the number of
      functional release sites induced by protein kinase A (PKA) cascade, we attempted
      to visualize functional release sites using styryl dyes, FM4-64 and FM1-43, and
      investigated the effects of PKA on the release sites. A PKA activator FSK
      increased the number of active release sites by approximately 20-30%. A direct
      PKA activator, Sp-cAMPS, showed the same effect, which was blocked by a PKA
      inhibitor, KT5720, suggesting that this effect was mediated by PKA. This PKA
      dependent increase in the number of release sites requires Ca(2+) in the bath
      solution, and Sr(2+) can not be a substitute for Ca(2+). Since the number of
      functional release sites is approximately half the total number of synaptophysin
      immunoreactive sites, the PKA dependent activation of silent release sites of DG
      neuron terminals is suggested.

PMID- 11535298
TI  - Effects of facial affect recognition on the auditory P300 in healthy subjects.
AB  - We examined the effects of facial affect recognition on auditory ERP using facial
      drawings depicting sadness, no emotion, pleasure and anger. Auditory ERP were
      recorded using an oddball paradigm in 13 women and 13 men while pictures and test
      tones were presented. P300 peak amplitude, area, and latency, and also subject's
      reaction time, were evaluated. The face showing pleasure resulted in the smallest
      P300 peak amplitude. Amplitudes were successively greater with anger, sadness,
      and no emotion. The P300 area showed facial affect effects resembling effects on
      peak amplitude. However, facial expression influenced P300 latency in different
      patterns suggesting the involvement of independent mechanisms. The
      reproducibility between sessions of the P300 measurements was tested. Both the
      P300 amplitude and area were largest when viewing neutral pictures, but smallest
      when viewing pleasant pictures in both sessions. While amplitude and the area of
      P300 were significantly larger in women than in men, gender was a less potent
      modifier of the influence of facial expression on P300 parameters. Reduced P300
      amplitude and area apparently reflected an inhibitory effect of attention by
      emotion from facial expressions, especially for pleasure.

PMID- 11535299
TI  - Directional asymmetry of nystagmus elicitation in humans during step and
      sinusoidal modes of lateral linear acceleration.
AB  - We investigated nystagmus elicitation in 50 normal subjects who were exposed
      interaurally to linear acceleration with step (rectangular) and sinusoidal modes
      of oscillation using a linear accelerator. Relatively strong G-loads of 0.3-0.5 G
      at a 10 m stroke were applied to subjects who looked at a memorized target in
      darkness, with the head and trunk tightly restrained in the upright sitting
      position. Horizontal and vertical eye movements were recorded by
      electrooculography (EOG). Various levels of G-directional preponderance (DP),
      including completely one-sided, were observed similarly in either stimulus mode,
      strongly suggesting that directional asymmetry in nystagmus elicitation may be a
      functional characteristic in the otolith-ocular response, in contrast to the
      canal-ocular response. The effects of G-load increase were less congruent between
      the two stimulus modes. In the step-mode oscillation, the desaccaded slow eye
      position which corresponds to the vestibuloocular reflex (VOR) was saw-toothed in
      shape as was the stimulus velocity curve, but the baseline often drifted slowly
      and DP-dependently in the direction opposite to the fast phase of nystagmus. When
      the slow phase velocity (SPV), a slope of the saw-tooth, was adjusted
      mathematically for such slow drift, it revealed that the adjusted SPVs were
      almost symmetrical between rightward and leftward G-directions. These results
      suggest that DP generation is separate from VOR generation which is primarily
      symmetrical.

PMID- 11535304
TI  - Anaphylaxis to the 23-valent pneumococcal vaccine in child: a case-control study
      based on immediate responses in skin tests and specific IgE determination.
AB  - Injections of the 23-valent pneumococcal vaccine are usually well tolerated. Skin
      tests (prick and intradermal) and a self-made RAST with pneumococcal vaccine and
      phenol were performed in a child reporting a severe anaphylactic reaction induced
      by a 23-valent pneumococcal vaccine, and in ten control children, including one
      child with a well-tolerated vaccination, and nine non-vaccinated children. Skin
      tests and RAST with the vaccine were positive in the child reporting anaphylaxis,
      and negative in nine of the control children. Intradermal test with the vaccine
      was slightly positive in a non-vaccinated child with negative RAST. Skin tests
      and RAST with phenol were negative in all the children. These results suggest
      that immediate responses in skin tests and specific IgE determination have a good
      diagnostic value in children reporting severe reactions suggestive of IgE
      dependent hypersensitivity to pneumococcal vaccine.

PMID- 11535305
TI  - Natural immunity to Haemophilus influenza b in infancy in Indian children.

PMID- 11535306
TI  - A prime-boost immunisation regimen using DNA followed by recombinant modified
      vaccinia virus Ankara induces strong cellular immune responses against the
      Plasmodium falciparum TRAP antigen in chimpanzees.
AB  - Two chimpanzees were vaccinated intramuscularly against malaria using plasmid DNA
      expressing the pre-erythrocytic antigens thrombospondin related adhesion protein
      (PfTRAP) and liver stage specific antigen-1 (PfLSA-1) of Plasmodium falciparum
      together with GM-CSF protein. A recombinant modified vaccinia virus Ankara (MVA)
      expressing PfTRAP was injected intramuscularly 6 weeks later to boost the immune
      response. This sequence of antigen delivery induced a specific and long-lasting T
      cell and antibody response to PfTRAP as detected by ELISPOT assay and ELISA.
      Antibody responses were detected after four DNA injections, and were boosted by
      injection of recombinant MVA expressing PfTRAP. Interferon-gamma secreting
      antigen-specific T cells were detected in both animals, but only after boosting
      with recombinant MVA. By screening a panel of PfTRAP-derived peptides, an epitope
      was identified that was recognized by cytotoxic T lymphocytes in one of the
      chimpanzees studied. T cells specific for this epitope were present in PBMCs and
      liver-infiltrating lymphocytes at a frequency of between 1 in 200 and 1 in 500.
      The high immunogenicity of this prime-boost regimen in chimpanzees supports
      further assessment of this delivery strategy for the induction of protection
      against P. falciparum malaria in humans.

PMID- 11535307
TI  - Adamantylamide dipeptide as effective immunoadjuvant in rabbits and mice.
AB  - In the search for more potent and less toxic immunomodulators, adamantylamide
      dipeptide (AdDP) was synthesized by the covalent union of amantadine with the L
      alanyl-D-isoglutamine residue of muramyldipeptide (MDP). The present experiments
      demonstrate the ability of AdDP, co-administered with a protein immunogen, to
      raise or enhance a humoral response in immunized animals. BALB/c mice were
      immunized either by the intraperitoneal (ip) or oral route with ovalbumin (Ova)
      alone or combined with either AdDP or CpG oligonucleotide (ODN-CpG), a proved
      adjuvant. A clear adjuvant dose-response relationship was observed on the
      increment of Ova-specific serum antibody titers when AdDP was used as adjuvant,
      irrespectively of the administration route. The IgG isotype analysis showed that
      AdDP promotes a consistent increment in IgG1 antibodies associated with a
      dominant Th2 response pattern. When administered by the oral route, AdDP was at
      least as efficient as ODN-CpG as adjuvant. Similar results were obtained in
      rabbits immunized by the oral route, suggesting that the adjuvanticity of AdDP is
      not restricted to the murine system. In conclusion, AdDP was shown to be a
      powerful and non-toxic adjuvant at both systemic and mucosal levels, which makes
      it a promising tool for vaccine development.

PMID- 11535308
TI  - Characterization of antibody responses to annual influenza vaccination over four
      years in a healthy elderly population.
AB  - The effects of yearly influenza immunization on the level of antibody responses
      were assessed in 92 healthy elderly subjects immunized over four contiguous years
      (1993-1996) with a trivalent influenza vaccine that included A/Texas annually.
      Anti-A/Texas antibodies increased significantly and similarly post-vaccination
      each year, but returned to comparable baseline levels annually. Percentages of
      subjects with anti-A/Texas titers > or =40 post-vaccination were comparable over
      four years. Importantly, post-vaccination titers > or =40 to A/Texas in 1993-1994
      predicted anti-A/Texas titers > or =40 in subsequent years. Thirty percent of
      individuals produced four-fold rises to any vaccine component the first year it
      was included in the vaccine, however, this percentage decreased to about 10%
      after subsequent vaccination with the same component. This study clearly supports
      the concept that annual immunization with the same influenza vaccine component
      over multiple years does not significantly decrease antibody titers in a healthy
      elderly population.

PMID- 11535309
TI  - Immunization of woodchucks (Marmota monax) with hepatitis delta virus DNA
      vaccine.
AB  - We investigated the DNA immunization approach in order to induce a protective
      immune response against hepatitis delta virus (HDV) superinfection of chronically
      woodchuck hepatitis virus (WHV) infected woodchucks. The animals were immunized
      with an expression vector encoding HDAg by gene gun. T cell and humoral immune
      responses induced by this protocol were determined and compared with those
      induced by HDAg immunization using a CpG oligonucleotide as an adjuvant. After
      immunization the woodchucks were challenged with 10(6) genome equivalents of HDV.
      The protein immunization with HDAg induced good humoral and T helper cell
      responses in the woodchucks, but did not protect them from HDV superinfection.
      The DNA immunized woodchucks were also not protected from HDV superinfection,
      however, the course of infection was modified: HDV viremia occurred later, the
      typical fluctuation of the HDV RNA titer with several peaks was absent, and
      antibodies to HDV were not detectable.

PMID- 11535310
TI  - Data mining in the US Vaccine Adverse Event Reporting System (VAERS): early
      detection of intussusception and other events after rotavirus vaccination.
AB  - The Vaccine Adverse Event Reporting System (VAERS) is the US passive surveillance
      system monitoring vaccine safety. A major limitation of VAERS is the lack of
      denominator data (number of doses of administered vaccine), an element necessary
      for calculating reporting rates. Empirical Bayesian data mining, a data analysis
      method, utilizes the number of events reported for each vaccine and statistically
      screens the database for higher than expected vaccine-event combinations
      signaling a potential vaccine-associated event. This is the first study of data
      mining in VAERS designed to test the utility of this method to detect
      retrospectively a known side effect of vaccination-intussusception following
      rotavirus (RV) vaccine. From October 1998 to December 1999, 112 cases of
      intussusception were reported. The data mining method was able to detect a signal
      for RV-intussusception in February 1999 when only four cases were reported. These
      results demonstrate the utility of data mining to detect significant vaccine
      associated events at early date. Data mining appears to be an efficient and
      effective computer-based program that may enhance early detection of adverse
      events in passive surveillance systems.

PMID- 11535311
TI  - Immunogenicity, safety and lot consistency in adults of a chromatographically
      purified Vero-cell rabies vaccine: a randomized, double-blind trial with human
      diploid cell rabies vaccine.
AB  - The immunogenicity and safety of a chromatographically purified rabies vaccine
      (CPRV) was evaluated using US veterinary medical students. In the first study,
      242 healthy adults were enrolled in a randomized, modified double-blind,
      multicenter trial and received five doses of either CPRV or human diploid cell
      vaccine (HDCV) by intramuscular injection on days 0, 3, 7, 14, and 28
      concurrently with human rabies immunoglobulin in a simulated post-exposure
      prophylaxis regimen. Post-immunization titers in the CPRV and HDCV groups reached
      0.5 IU/ml (the WHO-recommended minimally acceptable titer) or greater in all
      subjects in both vaccine groups by day 14 and remained above that level through
      day 90. In the second study, 438 healthy adults were enrolled in a randomized,
      double-blind, multicenter trial and assigned to receive five doses from one of
      three lots of CPRV by intramuscular injection on days 0, 3, 7, 14, and 28 in a
      simulated post-exposure prophylaxis regimen to evaluate lot consistency. Post
      immunization titers rapidly increased to over 0.5 IU/ml by day 14 for all
      subjects and remained above that level through day 42 when the study was
      terminated. The three lots were considered equivalent. The percentage of subjects
      with at least one local reaction during the five-dose regimen was slightly lower
      in the CPRV group than in the HDCV group (P=0.06). The most frequently reported
      local reaction for all doses of vaccine was pain at the injection site. Headache,
      myalgia, and malaise were the most frequently reported systemic events. The
      percentage of subjects with at least one systemic event was significantly lower
      for CPRV (P=0.0084). No vaccine-related serious adverse reaction was reported in
      these studies. The results of these studies indicate that CPRV administered
      intramuscularly to healthy adults is immunogenic and is associated with fewer
      local and systemic reactions than HDCV.

PMID- 11535312
TI  - Measles seroepidemiology and decay rate of vaccine-induced measles IgG titers in
      Taiwan, 1995-1997.
AB  - Community-based seroepidemiologic studies were conducted to monitor the
      effectiveness of measles immunization programmes and to estimate the decay rate
      of vaccine-induced measles IgG titres. Sera collected from a mountain (792 sera),
      rural (875 sera) and urban (894 sera) populations in 1995-1997 were available.
      Measles IgG was quantified using a commercial EIA kit. Measles IgG seroprevalence
      and geometric mean titre (GMT) were calculated by setting the cut-off titre at 50
      mIU/ml. The decay rate of measles IgG titres was estimated by assuming that the
      measles IgG titres, without exposing to wild measles virus, decay exponentially
      and constantly after 1 year post vaccination. The half-life of measles IgG titres
      was calculated from the corresponding decay rate. Measles IgG seroprevalences in
      these three populations have reached >95% in school children (7-18 years old) and
      >98% in young adults (19-25 years old) but varied from 87 to 96% in pre-school
      children (4-6 years old). Two-dose vaccinees, comparing with 1-dose vaccinees,
      had a significantly higher seroprevalence (98 versus 92%, P<0.01) and a slightly
      longer half-life of measles IgG titres (61 versus 27 months, P=0.08) but the
      measles IgG GMT in the two groups did not differ significantly (675 versus 618
      mIU/ml, P=0.78).

PMID- 11535313
TI  - Optimization of epitope processing enhances immunogenicity of multiepitope DNA
      vaccines.
AB  - Experimental DNA vaccines comprised of multiple minimal cytotoxic T lymphocytes
      (CTL) epitopes can effectively induce broad CTL responses; however, such
      constructs frequently exhibit significant variation in epitope immunogenicity.
      Antigenicity assays utilizing human cells transfected with one such multiepitope
      construct revealed that the epitopes with poor immunogenicity were inefficiently
      processed in transfected cells. Compilation of a database of 94 epitope/flanking
      region combinations, for which immunogenicity was measured experimentally,
      revealed that the type of residue immediately following the carboxyl-terminus of
      the epitope exerted a prominent effect on immunogenicity. Experiments utilizing a
      variety of HBV-specific vaccine constructs demonstrated epitope immunogenicity
      could be modulated by the insertion of a single amino acid and the effect on
      immunogenicity could be ascribed to modulation of processing efficiency. These
      findings demonstrate that multiepitope DNA vaccines can be engineered to enhance
      CTL immunogenicity by increasing processing efficiency.

PMID- 11535314
TI  - Comparison of the protective efficacy of yeast-derived and Escherichia coli
      derived recombinant merozoite surface protein 4/5 against lethal challenge by
      Plasmodium yoelii.
AB  - The gene encoding the Plasmodium yoelii homologue of P. falciparum merozoite
      surface proteins 4 (MSP4) and 5 (MSP5) has been expressed in Escherichia coli and
      Saccharomyces cerevisiae. The protein contains a single epidermal growth factor
      (EGF)-like domain and is expressed in a form lacking the predicted N-terminal
      signal and glycosyl phosphatidylinositol (GPI) attachment sequences. The
      recombinant protein derived from E. coli (EcMSP4/5) was highly effective at
      protecting mice against lethal challenge with 10(5) parasites of the P. yoelii YM
      strain. In contrast, the protective efficacy of yeast-derived MSP4/5 (yMSP4/5)
      was considerably less. The antibody titres in both groups were significantly
      different with mice immunised with yeast-derived protein showing significantly
      lower pre-challenge antibody responses. There was a significant inverse
      correlation between antibody levels as measured by ELISA and peak parasitaemia.
      Mice immunised with EcMSP4/5 produced anti-PyMSP4/5 antibodies predominantly of
      the IgG2a and IgG2b isotypes, whereas, mice immunised with yMSP4/5 mainly
      produced antibodies of the IgG1 isotype. The differences in antibody titres and
      subtype distribution may account for the observed differences in protective
      efficacy of these protein preparations. Levels of protective efficacy of MSP4/5
      were compared with that obtained using P. yoelii MSP1 produced in S. cerevisiae.
      Levels of protection induced by E. coli derived MSP4/5 were superior to those
      induced by MSP1 which in turn were better than those induced by yeast-derived
      MSP4/5.

PMID- 11535315
TI  - Cytotoxic T cell polyepitope vaccines delivered by ISCOMs.
AB  - CD8 alphabeta cytotoxic T lymphocyte (CTL) polyepitope or polytope vaccines have
      traditionally been delivered using recombinant vector or DNA based delivery
      modalities. Here we show the delivery of polytope vaccines in the form of either
      synthetic polypeptides or recombinant polytope proteins by ImmunoStimulatory
      COMplexes (ISCOMs(R)). Induction of multiple protective CTL responses by these
      polytope-ISCOM formulations were comparable to viral vector or DNA based delivery
      modalities as assessed by IFNgamma ELISpot, chromium release and viral challenge
      assays. Measurement of CTL responses specific for the different epitopes revealed
      immunodominance patterns, which were largely independent of the vaccine vector or
      the order of the epitopes in the polytope. ISCOMs thus emerge as a viable human
      delivery modality for protein-based polytope vaccines.

PMID- 11535316
TI  - Safety and immunogenicity of live attenuated quadrivalent human-bovine (UK)
      reassortant rotavirus vaccine administered with childhood vaccines to infants.
AB  - The safety and immunogenicity of an orally administered, live rotavirus vaccine
      comprised of four strains, each with a titer of 10(5.3) or 10(5.8) pfu, and each
      having 10 genes from the UK bovine strain and the VP7 gene from human rotavirus
      serotype 1, 2, 3, or 4, were evaluated in adults, young children and infants in
      randomized, double-blind phase 1 trials. Three doses of rotavirus vaccine or
      placebo given with childhood immunizations to infants at 2, 4, and 6 months of
      age were well tolerated and did not inhibit antibody responses to childhood
      vaccines which included DTP, Hib, hepatitis B and OPV. Serum rotavirus antibody
      responses were detected in 12 of 20 infants after 1 dose, and in 19/19 of the
      vaccinees after three doses. Neutralizing antibody responses were detected more
      often against the bovine rotavirus UK strain (95%) than to human rotavirus VP7
      serotypes 1 (37%), 2 (32%), 3 (32%) or 4 (32%). The efficacy of this quadrivalent
      rotavirus vaccine needs to be evaluated further.

PMID- 11535317
TI  - Immunopotentiation of DNA vaccine against herpes simplex virus via co-delivery of
      plasmid DNA expressing CCR7 ligands.
AB  - The CCR7 ligands, secondary lymphoid tissue chemokine (SLC) and Epstein-Barr
      virus-induced molecule 1 ligand chemokine (ELC), were recently recognized as key
      molecules in establishing functional microenvironments for the initiation of
      immune responses in secondary lymphoid tissue. Here, we investigated the effect
      of CCR7 ligands-DNA administration on systemic and mucosal immune responses to
      plasmid DNA encoding gB of herpes simplex virus (HSV). Systemic co-transfer of
      both CCR7 ligands enhanced serum gB-specific IgG Ab but failed to elicit
      enhancement of distal mucosal IgA responses. In contrast, mucosal co-transfer
      provided significant increases of distal mucosal IgA responses. CCR7 ligands also
      enhanced T cell-mediated immunity as measured by CD4+ T helper cell proliferation
      and CD8+ T cell-mediated CTL activity. Of particular interest, is the observation
      that SLC significantly increased the production of Th1-type cytokines (IL-2 and
      IFN-gamma) (P<0.05), whereas ELC increased the production of both Th1-type and
      Th2-type (IL-4) cytokines (P<0.05). Moreover, co-vaccination of CCR7 ligands
      increased the number of dendritic cells in secondary lymphoid tissue. These data
      indicate that CCR7 ligands may prove to be useful adjuvants for genetic
      vaccination against intracellular infection as well as cancer.

PMID- 11535319
TI  - The utility of serologic testing for varicella in an adolescent population.
AB  - The purpose of this study was to determine what proportion of adolescents without
      a history of varicella are seropositive, and if serologic testing of this
      adolescent subpopulation is cost-effective. We identified 122 patients with 'no'
      or 'unknown' histories of chicken pox from our adolescent clinic. Of these, 58
      (48%) were found to be Varicella Zoster Virus (VZV) seropositive. Cost to the
      government for batched serologic testing of all unknowns was $682.65, while each
      adolescent vaccinated cost $59.60. Serologic testing prior to routine
      immunization of adolescents with unclear varicella histories saved $2774.15 (38%
      of routine immunization costs). In this population, serologic testing is more
      cost effective than routinely immunizing all unknowns.

PMID- 11535318
TI  - Induction of T lymphocyte responses to dengue virus by a candidate tetravalent
      live attenuated dengue virus vaccine.
AB  - Development of a safe and immunogenic tetravalent dengue virus (DV) vaccine has
      been designated as a priority by the World Health Organization. We characterized
      the T cell response to DV induced by a candidate live attenuated tetravalent DV
      vaccine as part of a phase I study. Proliferation and cytotoxic T lymphocyte
      (CTL) responses to multiple DV serotypes were detected in six of six and four of
      four subjects studied, respectively. Proliferation responses were higher to DV
      serotypes 1 and 3 than to serotypes 2 and 4. CTL responses were higher to DV
      serotypes 2 and 3 than to serotype 1, and included serotype cross-reactive
      responses. Production of interferon-gamma, but not IL-4, was observed in response
      to DV stimulation. This candidate vaccine is immunogenic for both CD4+ and CD8+ T
      lymphocytes. However, T cell responses to the four DV serotypes were not
      equivalent, suggesting that the vaccine could be further optimized.

PMID- 11535320
TI  - Safety and immunogenicity of varying dosages of trivalent inactivated influenza
      vaccine administered by needle-free jet injectors.
AB  - To evaluate the perceived pain, other adverse events, and immunogenicity of
      influenza virus vaccine administered by needle-free jet injector (JI) compared
      with that of vaccine administered by needle and syringe (N&S), we randomly
      assigned 304 healthy young adults to receive one of three dosages (0.5, 0.3, or
      0.2 ml) of the 1998-1999 season vaccine administered by either of two JI devices
      or by N&S. In multivariate analysis, female gender and JI administration were
      associated with higher levels of pain reported at the time of vaccination as well
      as with the occurrence of local injection site reactions following vaccination.
      Immune response did not vary significantly by dosage but administration by one JI
      device was associated with higher post-vaccination H1N1 antibody titers.

PMID- 11535321
TI  - A prospective, randomized, comparative US trial of a combination hepatitis A and
      B vaccine (Twinrix) with corresponding monovalent vaccines (Havrix and Engerix-B)
      in adults.
AB  - In an open, randomized, multicenter, controlled clinical trial in the US, 773
      adults were administered either a combination hepatitis vaccine (Twinrix: 720
      EL.U inactivated hepatitis A antigen and 20 mcg recombinant hepatitis B surface
      antigen per milliliter) on a 0, 1, 6 month schedule or corresponding monovalent
      vaccines concurrently (Havrix, 1440 EL.U/ml of hepatitis A antigen at 0, 6 months
      and Engerix-B, 20 mcg of hepatitis B surface antigen at 0, 1, 6 months). Non
      inferiority testing for the primary endpoint, severe soreness, and equivalence
      testing for the secondary endpoints, anti-HAV seroconversion and anti-HBs
      seroprotection, showed that safety and immunogenicity were comparable in the two
      groups.

PMID- 11535322
TI  - Assessment of injection site reactions to an acellular pertussis-based
      combination vaccine, including novel use of skin tests with vaccine antigens.
AB  - Recent reports indicate that children receiving a fifth consecutive dose of DTPa
      vaccine have a moderate likelihood of developing a large injection site reaction,
      the etiology of which remains unknown. We assessed the frequency, severity and
      outcome of local reactions in 205 children who had participated in earlier
      studies of DTPa-based vaccines and were due for a fifth dose at 4-6 years.
      DTPa.IPV vaccine was given intramuscularly in the deltoid. To explore the role of
      cell-mediated immunity in local reactions we applied epicutaneous (patch) tests
      at the same visit, using code-labeled solutions of DTPa.IPV, DT, Pa, IPV, alum
      solution and saline, leaving them in place for 48 h. Subjects were assessed by
      research staff on the following day. Injection site redness or swelling >/=50 mm
      diameter was present in 24.4 and 20.5%, respectively, but none of the subjects
      had fever or persistent limitation of arm movement. Large local reactions were
      more common in bigger children (P<0.01) but not in those with allergy/atopy.
      Large reactions resolved within 14 days. Positive skin tests (erythema) occurred
      at 85 test sites in 51 of 187 evaluable children, principally with DTPa.IPV, IPV
      and alum solutions. However, only DT and Pa solutions caused positive tests
      significantly more often in children with injection site redness > or =50 mm than
      in non-reactors (P < 0.05, odds ratios 5.2 and 6.1, respectively). Presence of
      alum in most test solutions might have confounded the results as it caused non
      specific inflammation when applied alone. We conclude that local reactions to a
      fifth dose of DTPa-type vaccine are frequent and sometimes extensive but not
      incapacitating and that concurrent skin testing has potential to identify the
      vaccine antigens and immune mechanism contributing to local reactions with more
      refinement of the method.

PMID- 11535323
TI  - A randomized study of a flexible booster dosing regimen of VAQTA in adults:
      safety, tolerability, and immunogenicity.
AB  - BACKGROUND: VAQTA (hepatitis A vaccine inactivated, Merck & Co., Inc., West
      Point, PA) is licensed for use in healthy adults in a two-dose schedule at 0 and
      6 months. OBJECTIVE: to determine whether the responses to a booster dose of
      VAQTA administered to adults 12 or 18 months after the first dose were similar to
      the response when the booster dose was administered 6 months after the first
      dose. METHODS: healthy adults were randomized to receive 50-U of VAQTA at 6
      (Group I), 12 (Group II), or 18 months (Group III) following receipt of Dose 1 on
      Day 0. Blood samples were collected immediately prior to Doses 1 and 2 and then,
      4 weeks following Dose 2. Seropositivity rates (SPRs), geometric mean titers
      (GMTs) in milli-international units per milliliter (mIU/ml) and booster response
      rates (BRRs) were compared among treatment groups. Safety data were collected on
      Vaccination Report Cards. RESULTS: no serious adverse experiences were reported,
      and the vaccine was well-tolerated by subjects in the three treatment groups. One
      month following the booster dose, SPRs and GMTs for Groups I, II, and III,
      respectively, were, 100% (102/102) and 6726.4 mIU/ml; 97.9% (93/95) and 4863.8
      mIU/ml; 100% (86/86) and 6068.3 mIU/ml. The BRRs were 88.2% (Group I), 90.2%
      (Group II) and 94.2% (Group III). CONCLUSION: responses to the booster dose were
      comparable regardless of the timing (i.e. 6, 12, or 18 months following Dose 1).
      Flexibility in the timing of the booster dose of VAQTA in adults would allow the
      vaccination schedule to be the same for adults, adolescents, and children and may
      increase the likelihood that adults receive the booster dose.

PMID- 11535324
TI  - Microsphere translocation and immunopotentiation in systemic tissues following
      intranasal administration.
AB  - With a view to developing improved mucosal immunisation strategies, we have
      quantitatively investigated the uptake of fluorescent polystyrene carboxylate
      microspheres (1.1 microm diameter), using histology and fluorescence-activated
      cell sorting, following intranasal delivery to BALB/c mice. To qualify these
      biodistribution data, antigen specific memory and effector responses in the
      spleens of mice immunised nasally with Yersinia pestis V antigen loaded
      poly(lactide) (PLA) microspheres (1.5 microm diameter) were assessed at 4, 7 and
      11 days. Irrespective of administration vehicle volume (10 or 50 microl),
      appreciable numbers of fluorescent microspheres were detected within nasal
      associated lymphoid tissues (NALT) and draining cervical lymph nodes. Nasal
      administration of the particles suspended in 50 microl volumes of phosphate
      buffered saline (PBS) served to deposit the fluorescent microspheres throughout
      the respiratory tract (P<0.05). In these animals, appreciable particle uptake
      into the mediastinal lymph node was noted (P<0.05). Also, spleens removed from
      mice 10 days after fluorescent particle application contained significantly more
      microspheres if the suspension had been nasally instilled using a 50 microl
      volume (P<0.05). Appreciable memory (and effector from day 7) responses were
      detected in mediastinal lymph nodes removed from mice immunised nasally with 50
      microl volumes of microparticulated or soluble V antigen. Immunological responses
      in splenic tissue removed 7 days after intranasal immunisation corroborated the
      thesis that the spleen can act as an inductive site following bronchopulmonary
      deposition of particulated antigen: upon exposure to V in vitro, splenic T-cells
      from mice nasally immunised with 50 microl volumes of microspheres incorporated
      statistically greater (P<0.05) quantities of [3H]thymidine into newly synthesised
      DNA than did T-cells from cohorts nasally immunised with 50 microl volumes of V
      in solution. Similarly, significant numbers of anti-V IgG secreting cells were
      only detected in spleens from mice immunised intramuscularly or nasally with
      microparticles. These immunological and biodistribution data support the tenet
      that, following an appropriate method of mucosal delivery, microparticles can
      translocate to tissues in the systemic compartment of the immune system and
      thence provoke immunological reactions therein.

PMID- 11535325
TI  - The effect of zanamivir treatment on the early immune response to influenza
      vaccination.
AB  - Zanamivir is licensed for influenza treatment, but may also play a role in
      prophylaxis either alone or in combination with vaccine in epidemic periods. We
      conducted a double blind placebo controlled trial to investigate the effect of
      zanamivir treatment on the humoral immune response to influenza vaccine. Forty
      young healthy volunteers were vaccinated with licensed trivalent influenza
      vaccine and received 20 mg zanamivir (24 subjects) or placebo (16 subjects) daily
      for a period of 14 days. No significant differences were observed in the
      magnitude or the time course of the antibody response to the influenza H3N2 and B
      strains between the two groups, in contrast the placebo group responded with
      higher antibody titres to the H1N1. Our results suggest that during an influenza
      epidemic, volunteers would only need to continue zanamivir treatment for the
      initial 12 days after vaccination whilst the vaccine induced protective antibody
      response developed.

PMID- 11535326
TI  - Induction of cross clade reactive specific antibodies in mice by conjugates of
      HGP-30 (peptide analog of HIV-1(SF2) p17) and peptide segments of human beta-2
      microglobulin or MHC II beta chain.
AB  - HGP-30, a 30 amino acid synthetic peptide homologous to a conserved region of HIV
      1(SF2) p17 (aa86-115), has previously been shown to elicit both cellular and
      humoral immune responses when conjugated to KLH and adsorbed to alum. However,
      the free HGP-30 peptide is not immunogenic in animals. In order to improve the
      immunogenicity of HGP-30, peptide conjugates consisting of a modified HGP-30
      sequence (m-HGP-30/aa82-111) and a peptide segment, residues 38-50, of the MHC I
      accessory molecule, human beta-2-microglobulin (beta-2-M), referred to as Peptide
      J, or a peptide from the MHC II beta chain (peptide G) were evaluated in mice.
      The effects of carriers and adjuvants on serum antibody titers, specificities to
      various HIV-1 clade peptides similar to HGP-30 and isotype patterns were
      examined. Peptides J or especially G conjugated to modified-HGP-30 (LEAPS 102 and
      LEAPS 101, respectively) generated comparable or better immune responses to
      modified HGP-30 than KLH conjugates as judged by the induction of: (1) similar
      antibody titers; (2) broader HIV clade antigen binding; and (3) antibody isotype
      response patterns indicative of a TH1 pathway (i.e. increased amounts of IgG2a
      and IgG2b antibodies). The ISA 51 and MPL(R)-SE adjuvants induced higher antibody
      responses than alum, with the ISA 51 being more potent. Immune responses to LEAPS
      102, as compared to LEAPS 101, were weaker and slower to develop as determined by
      antibody titers and cross clade reactivity of the antibodies induced. Compared to
      KLH conjugates which induced significant anti-KLH antibody titers, minimal
      antibody responses were observed to peptide G, the more immunogenic conjugate,
      and peptide J. These results suggest that modified HGP-30 L.E.A.P.S. constructs
      may be useful as HIV vaccine candidates for preferential induction of TH1
      directed cell mediated immune responses.

PMID- 11535327
TI  - Importance of patients' perceptions and general practitioners' recommendations in
      understanding missed opportunities for immunisations in Swiss adults.
AB  - Over the last decades, tremendous efforts have been made to strengthen childhood
      immunisation programs. However, the burden of influenza and pneumococcal
      infections remains disturbingly high in adults and elderly. We conducted a cross
      sectional self-administered mail survey to identify characteristics associated
      with low use of recommended vaccines in adult patients attending routine primary
      care appointments in Switzerland. Tetanus vaccination was reported by 84% of
      respondents aged 16-34, and by only 42% of respondents aged 65 or more. For
      influenza and pneumococcal vaccination, of high-risk patients (age > or =65 or
      history of diabetes, kidney, heart, or chronic pulmonary disease), only 41% were
      on schedule for influenza and 6% for pneumococcal vaccination. Compared with
      patients from the German- and Italian-speaking areas of the country, patients
      from the French-speaking region were more likely to report past immunisation
      against influenza and pneumococcal disease or a recent physician's recommendation
      for immunisation against influenza, but equally likely to have ever refused
      influenza vaccination. For all three diseases, area of residence, physician's
      recommendation for immunisation, and patient's perceived usefulness of
      vaccination were independently and significantly associated with vaccination
      status. Although patient's opinion is an important determinant of vaccination
      coverage in adults, lack of physician's encouragement accounted for most missed
      vaccination opportunities in this study. The higher vaccination coverage among
      patients from the French-speaking area suggests that the promotion campaigns
      carried out in this region effectively improved influenza vaccine use.
      Interventions designed to increase vaccination coverage in adults must help
      providers incorporate immunisation in routine health care.

PMID- 11535328
TI  - In vitro correlate of immunity in a rabbit model of inhalational anthrax.
AB  - A serological correlate of vaccine-induced immunity was identified in the rabbit
      model of inhalational anthrax. Animals were inoculated intramuscularly at 0 and 4
      weeks with varying doses of Anthrax Vaccine Adsorbed (AVA) ranging from a human
      dose to a 1:256 dilution in phosphate-buffered saline (PBS). At 6 and 10 weeks,
      both the quantitative anti-protective antigen (PA) IgG ELISA and the toxin
      neutralizing antibody (TNA) assays were used to measure antibody levels to PA.
      Rabbits were aerosol-challenged at 10 weeks with a lethal dose (84-133 LD(50)) of
      Bacillus anthracis spores. All the rabbits that received the undiluted and 1:4
      dilution of vaccine survived, whereas those receiving the higher dilutions of
      vaccine (1:16, 1:64 and 1:256) had deaths in their groups. Results showed that
      antibody levels to PA at both 6 and 10 weeks were significant (P<0.0001)
      predictors of survival.

PMID- 11535329
TI  - Evaluation of European tick-borne encephalitis virus vaccine against recent
      Siberian and far-eastern subtype strains.
AB  - To evaluate the efficacy of the European TBE vaccine in east-Siberian and far
      eastern regions of Russia, we examined the immune responses of the vaccine
      against recent TBE virus Siberian (Irkutsk) and far-eastern (Khabarovsk and
      Vladivostok) isolates. The sera of vaccinated humans showed efficient
      neutralizing antibody titers (> or =20) against Siberian and far-eastern strains.
      To evaluate the efficacy of the vaccine in vivo, mice were vaccinated and
      challenged with lethal doses of the viruses. All vaccinated mice survived each
      virus challenge. These results suggest that the European vaccine can prevent the
      TBE virus infection in east-Siberian and far-eastern regions of Russia.

PMID- 11535330
TI  - Efficacy of pneumococcal polysaccharide vaccine in immunocompetent adults: a meta
      analysis of randomized trials.
AB  - The use of pneumococcal polysaccharide vaccine (PPV) is low in some countries,
      maybe because of doubts regarding its efficacy. This meta-analysis aims at
      combining evidence from randomized trials of PPV assessing its efficacy in
      preventing Streptococcus pneumoniae related diseases in immunocompetent adults.
      In the fourteen trials totalling 48,837 patients retrieved, PPV prevents definite
      pneumococcal pneumonia by 71%, presumptive pneumococcal pneumonia by 40%, and
      mortality due to pneumonia by 32%, but not all-cause pneumonia or death. No
      preventive effect was seen in the subgroup of patients aged 55 years or more,
      possibly due to a lack of statistical power.

PMID- 11535331
TI  - Hospital admissions for pertussis in Spain, 1995-1998.
AB  - This epidemiological survey was undertaken to estimate the annual burden of
      hospitalizations for pertussis in Spain during a four-year period 1995-1998. Data
      were obtained from the national surveillance system for hospital data. All
      hospital discharges for pertussis (ICD-9- CM 033) were analyzed. The annual
      incidence of hospitalization for pertussis was 1.7 per 100,000 population. Eighty
      nine percent of the cases were < 1 year of age (incidence of 78 per 100,000) and
      95% were < or =5 years of age (incidence of 28 per 100,000). During the study
      period, 14 deaths were reported among patients hospitalized by pertussis. Despite
      of the high immunization rates, many pertussis cases occur each year, mostly of
      them among very young children.

PMID- 11535332
TI  - Latency and reactivation of a glycoprotein E negative bovine herpesvirus type 1
      vaccine: influence of virus load and effect of specific maternal antibodies.
AB  - The effects of the vaccination of neonatal calves with a glycoprotein E (gE)
      negative bovine herpesvirus type 1 (BHV-1) were investigated in naive and
      passively immunised calves either with the recommended dose or a 5-fold
      concentrated one. After inoculation (PI), all calves excreted the virus vaccine
      except three passively immunised calves inoculated with the lower titre. No
      antibody response could be detected in passively immunised calves, whatever the
      dose used, and they all became BHV-1 seronegative and remained so after
      dexamethasone treatment (PDT). Nevertheless, as shown by a gamma-interferon
      assay, all calves that excreted the vaccine PI developed a cell-mediated immune
      response and a booster response was observed PDT, suggesting viral reactivation.
      The vaccine virus was recovered PDT from nasal secretions in two calves and BHV-1
      DNA were detected in trigeminal ganglia from five calves belonging to all
      inoculated groups. The results show that the BHV-1 gE-negative vaccine can
      establish latency not only in naive but also in passively immunised neonatal
      calves after a single intranasal inoculation. Moreover, this study shows for the
      first time that the gE-negative vaccine, when used in passively immunised calves,
      can lead to seronegative vaccine virus carriers.

PMID- 11535333
TI  - Kinetics of humoral immune response after rabies VR-G oral vaccination of captive
      fox cubs (Vulpes vulpes) with or without maternally derived antibodies against
      the vaccine.
AB  - In western Europe during the spring, the largest proportion of fox populations
      are cubs and the key to successful rabies oral vaccination campaigns is cub
      vaccination. In this paper we report on studies of the serology of 93 fox (Vulpes
      vulpes) cubs born to unvaccinated and orally vaccinated captive vixens, some of
      which were orally vaccinated at 30 or at 90 days of age with the vaccinia
      recombinant vaccine (VR-G) that expresses the rabies virus glycoprotein. The
      duration of cub passively acquired antibody, the development of immune responses
      to oral vaccination at either 30 or 90 days of age, possible interference between
      passive and active immunity to such vaccination and resistance to a potentially
      lethal rabies challenge dose when five months old were measured. The study showed
      that rabies neutralising antibody can be passed to their cubs by vixens orally
      vaccinated with VR-G during pregnancy. Maternally derived antibody titres in cubs
      declined with time and disappeared by 45-75 days after birth. Thirty days old
      cubs serologically responded to oral vaccination. No interference between
      antibody of maternal origin and active immunity conferred by VR-G oral
      vaccination or between antibody of maternal origin and protection was observed.
      Thus, very young cub immunisation against rabies with VR-G per os is possible
      whatever the immune status of their mothers. Provided a vaccine-bait suitable for
      such young cubs exists, oral vaccination at den entrances with VR-G is a
      feasibility.

PMID- 11535334
TI  - Immune responses in goats to recombinant hemagglutinin-neuraminidase glycoprotein
      of Peste des petits ruminants virus: identification of a T cell determinant.
AB  - Peste des petits ruminants virus (PPRV), a member of the genus Morbillivirus
      within the family Paramyxoviridae, causes a fatal disease 'peste des petits
      ruminants' in goats and sheep. This enveloped virus is antigenically closely
      related to rinderpest virus (RPV), which causes a similar but distinct disease in
      large ruminants. PPRV harbors two major surface glycoproteins, the hemagglutinin
      neuraminidase (HN) and the fusion (F) proteins. The surface glycoproteins of
      morbilliviruses are highly immunogenic and confer protective immunity. In this
      study, we investigated the immune responses generated in goats immunized with low
      doses of purified recombinant extracellular baculovirus carrying a membrane bound
      form of the HN protein of PPRV without any adjuvant. We report that the immunized
      goats develop both humoral and cell-mediated immune responses. Antibodies
      generated in the immunized animals could neutralize both PPRV and RPV in vitro.
      Further, using a combination of Escherichia coli expressed deletion mutants of
      PPRV-HN and RPV-H proteins, and synthetic peptides corresponding to the highly
      conserved N-terminal sequences of MV-H protein, we have mapped an N-terminal T
      cell determinant (amino acids 123-137) and a C-terminal domain (amino acids 242
      609) harboring potential T cell determinant(s) in goats.

PMID- 11535335
TI  - Onjisaponins, from the root of Polygala tenuifolia Willdenow, as effective
      adjuvants for nasal influenza and diphtheria-pertussis-tetanus vaccines.
AB  - Active substances from hot water extracts from 267 different Chinese and Japanese
      medicinal herbs were screened for mucosal adjuvant activity with influenza HA
      vaccine in mice. The extract from the root of Polygala tenuifolia was found to
      contain potent mucosal adjuvant activity. The active substances were purified and
      identified as onjisaponins A, E, F, and G. When each onjisaponin (10 microg) was
      intranasally (i.n.) inoculated with influenza vaccine (10 microg) in mice, serum
      hemagglutination-inhibiting (HI) antibody titers increased 3-14 times over
      control mice administered vaccine alone after 4 weeks. When each onjisaponin (10
      microg) was i.n. inoculated with the vaccine (10 microg) followed by i.n.
      vaccination of the vaccine alone after 3 weeks, serum HI antibody titers
      increased 27-50 fold over those mice given i.n. vaccinations without
      onjisaponins. These same conditions also significantly increased nasal anti
      influenza virus IgA antibody titers. Two inoculations with onjisaponin F (1
      microg) and influenza HA vaccine (1 microg) at 3 weeks intervals, significantly
      increased serum HI antibody and nasal anti-influenza virus IgA and IgG antibody
      titers after only 1 week over mice given HA vaccine alone after the secondary
      vaccination. Intranasal vaccination with onjisaponin F inhibited proliferation of
      mouse adapted influenza virus A/PR/8/34 in bronchoalveolar lavages of infected
      mice. Separate intranasal vaccinations with onjisaponins A, E, F, and G (10
      microg) each and diphtheria-pertussis-tetanus (DPT) vaccine (10 microg) of mice
      followed by i.n. vaccination with DPT vaccine alone after 4 weeks showed
      significant increases in serum IgG and nasal IgA antibody titers after 2 weeks
      following secondary vaccination over mice vaccinated with DPT vaccine alone. All
      onjisaponins showed little hemolytic activity at concentrations up to 100
      microg/ml. The results of this study suggest that onjisaponins may provide safe
      and potent adjuvants for intranasal inoculation of influenza HA and DPT vaccines.

PMID- 11535336
TI  - Comparative immunogenicity and safety of two dosing schedules of a combined
      hepatitis A and B vaccine in healthy adolescent volunteers: an open, randomised
      study.
AB  - An open, randomised study was undertaken to demonstrate the equivalence in
      immunogenicity and to determine the reactogenicity and safety of two dosing
      schedules (0, 6 or 0, 12 month) of an adult formulation of a combined hepatitis A
      and B vaccine containing 720 EL.U. of inactivated hepatitis A antigen and 20
      microg of hepatitis B surface antigen (Twinrix, SmithKline Beecham Biologicals,
      Belgium) in 240 healthy volunteers aged 12-15 years. The vaccine was well
      tolerated when administered using either vaccination schedule. At month 7, 98.1%
      of subjects completing the 0, 6 month vaccination schedule were seroprotected
      against hepatitis B (anti-hepatitis B surface antigen (anti-HBs) > or =10 mIU/ml)
      and 100% were seropositive for anti-hepatitis A virus (anti-HAV) antibodies
      (i.e., > or =33 mIU/ml). The corresponding geometric mean titres (GMTs) were 2791
      mIU/ml for anti-HBs and 5992 mIU/ml for anti-HAV antibodies. At month 13, 97% of
      subjects assigned to the 0, 12 month vaccination schedule were protected against
      hepatitis B and 99% were seropositive for anti-HAV antibodies. The corresponding
      GMTs were 4340 and 8472 mIU/ml, respectively. A combined response (i.e.,
      subjects, who were seropositive for anti-HAV antibodies and seroprotected for
      anti-HBs antibodies) was achieved in 98% of subjects vaccinated according to the
      0, 6 month interval and in 96% of subjects vaccinated using the 0, 12 month
      schedule. The reactogenicity of both vaccination schedules was also equivalent.
      The results thus show that the combined hepatitis A and B vaccine can be
      administered using flexible vaccination intervals, which make it suitable for use
      in large-scale hepatitis immunisation programmes.

PMID- 11535337
TI  - Bordetella bronchiseptica fimbrial protein-enhanced immunogenicity of a
      Mannheimia haemolytica leukotoxin fragment.
AB  - Leukotoxin produced by Mannheimia (Pasteurella) haemolytica is an important
      virulence factor in shipping fever pneumonia in feedlot cattle and is a critical
      protective antigen. In this study, the immune response to a chimeric protein
      generated by combining a gene fragment encoding neutralizing epitopes of M.
      haemolytica leukotoxin and a fimbrial protein gene (fim N) from Bordetella
      bronchiseptica was evaluated. The recombinant gene was cloned in a bacterial
      expression vector under the control of the tac promoter and expressed as a fusion
      protein with glutathione-S-transferase (GST) in Escherichia coli. Immunization of
      mice with the recombinant protein, GST-LTXFIM elicited a significantly stronger
      anti-leukotoxin antibody response than comparable immunizations with GST-LTX
      fusion proteins lacking FIM N. The GST-LTXFIM was also more stable than GST-LTX
      during storage at -80 degrees C, thus alleviating a stability problem inherent to
      leukotoxin. This chimeric protein may be a candidate for inclusion in new
      generation vaccines against shipping fever pneumonia.

PMID- 11535338
TI  - Passive immunization with Neisseria meningitidis PorA specific immune sera
      reduces nasopharyngeal colonization of group B meningococcus in an infant rat
      nasal challenge model.
AB  - To examine the protective efficacy of specific immune sera generated by
      meningococcal vaccine candidates against nasopharyngeal colonization, we
      developed an infant rat nasal colonization model for group B meningococcus. In
      this model, Sprague-Dawley infant rats were challenged intranasally in with host
      adapted, piliated Neisseria meningitidis group B strains H355 or H44/76
      administered concurrently with iron dextran. Colonization was assessed by
      quantitative culture of nasal homogenates and expressed as log(10) colony forming
      units (c.f.u.) per nose. Three to five log(10) c.f.u. of N. meningitidis were
      routinely recovered from the nasal tissue up to 4 days post-challenge. Passive
      immunization (i.p.) of the infant rats with either PorA or whole cell antisera 24
      h prior to homologous challenge resulted in a significant reduction of N.
      meningitidis colonization in the nasal tissues of these animals. These results
      demonstrate that this model can be utilized to evaluate the role of antibody to
      prevent the initial nasopharyngeal colonization by group B meningococcus.

PMID- 11535339
TI  - Attitudes of homoeopathic physicians towards vaccination.
AB  - Vaccinations are one of the most effective preventive procedures in modern
      medicine. However, earlier studies have indicated that homoeopathic physicians do
      not recommend or apply vaccinations as frequently as their allopathic colleagues.
      Few studies have been undertaken to clarify this question and most of these have
      not distinguished between medically and non-medically qualified homoeopathic
      practitioners. Therefore, misunderstandings have arisen concerning this question.
      In the study presented only medically qualified colleagues were included. In the
      course of this study, 219 medically qualified homoeopathic and 281 non
      homoeopathic physicians in Germany (response rate 30.4%) returned a questionnaire
      about the application and recommendation of 17 different vaccinations in their
      practices. The answers show that the responding homoeopathic physicians do not
      generally refuse vaccines but rather view them with a specific hierarchy. The
      'classical' vaccines against tetanus, diphtheria and poliomyelitis are applied to
      nearly the same degree as by non-homoeopathic colleagues. Vaccines against
      childhood diseases, risk group vaccinations and vaccinations judged as
      ineffective are applied and accepted with more restraint by homoeopathic
      physicians.

PMID- 11535340
TI  - Immunogenicity of a DNA vaccine against herpes B virus in mice and rhesus
      macaques.
AB  - Herpes B virus (Cercopithecine herpesvirus 1) is endemic in captive macaque
      populations and poses a serious threat to humans who work with macaques or their
      tissues. A vaccine that could prevent or limit B virus infection in macaques
      would lessen occupational risk. To that end, a DNA vaccine plasmid expressing the
      B virus glycoprotein B (gB) was constructed and tested for immunogenicity in mice
      and macaques. Intramuscular (IM) or intradermal (ID) immunization in mice
      elicited antibodies to gB that were relatively stable over time and predominately
      of the IgG2a isotype. Five juvenile macaques were immunized by either IM+ID (n=2)
      or IM (n=3) routes, with two booster immunizations at 10 and 30 weeks. All five
      animals developed antibodies to B virus gB, with detectable neutralizing activity
      in the IM+ID immunized animals. These results demonstrated that DNA immunization
      can be used to generate an immune response against a B virus glycoprotein in
      uninfected macaques.

PMID- 11535341
TI  - CpG containing oligodeoxynucleotides are potent adjuvants for parenteral
      vaccination with the fusion (F) protein of respiratory syncytial virus (RSV).
AB  - The feasibility of using oligodeoxynucleotides (ODN) containing unmethylated CpG
      motifs as parenteral adjuvants for subunit vaccines against RSV was tested in
      BALB/c mice. Compared with immunization with natural F protein adsorbed to
      aluminum hydroxide (F/AlOH) adjuvant alone, coadministration of F/AlOH with CpG
      ODN resulted in statistically significant increases in serum neutralization
      titers, an enhanced generation of splenic antigen-dependent killer cell
      precursors, and accelerated clearance of infectious virus from lungs 4 days after
      challenge. The statistically significant increases in serum IFNgamma and anti-F
      protein IgG2a titers, and significantly diminished pulmonary IL-5 and
      eosinophilia after challenge indicated that CpG ODN enhanced the ability of
      F/AlOH to elicit type 1 immune responses. F protein-specific serum IgE titers
      were also reduced. Further analysis of pulmonary inflammatory cells demonstrated
      an expansion of CD8(+) T cells, relative to the CD4(+) T cell compartment. The
      potency of CpG ODN was not adversely affected in gene knockout mice devoid of the
      p35 chain of the IL-12 heterodimer. Taken together, the results suggest a novel
      formulation for naive recipients of F protein-based subunit vaccines that does
      not result in a type 2 phenotype.

PMID- 11535342
TI  - Sterilizing immunity against experimental Helicobacter pylori infection is
      challenge-strain dependent.
AB  - The development of a murine model of Helicobacter pylori infection through serial
      in vivo passage of candidate strains has enabled a quantitative assessment of
      vaccine efficacy. In this study we compare infection with and protection against
      challenge from both CagA(+) type I, and CagA(-) type II in vivo adapted isolates.
      In vivo passage of a type II H. pylori isolate resulted in a highly infectious
      strain (X47-2AL), capable of reproducibly infecting mice to high density (10(7)
      CFU/g of gastric tissue). Similarly adapted type I strains were found to colonize
      mice at a significantly lower level (10(4)-10(5) CFU/g tissue). Mucosal
      immunization with recombinant urease (rUre) significantly protected animals
      against both types. Protection against X47-2AL was characterized by a > or =100
      fold (or 2 log) reduction in bacterial density. However, the presence of a
      residual infection highlighted the inability to achieve sterilizing immunity
      against this strain. The level of protection appeared independent of challenge
      dose, and was stable for up to 6 months, all animals exhibiting a low-level
      residual infection that did not recrudesce with time. Similarly immunized mice
      challenged with isolates representing the residual infection were also protected,
      confirming that they did not represent a sub-population of H. pylori that could
      escape immunity. Immunization and challenge studies with type I adapted-isolates,
      demonstrated a similar 2-3 log reduction in the bacterial burden, but that in
      this instance resulted in sterilizing immunity. These results suggest varied
      specificity for the murine host by different Helicobacter strains that can
      influence the outcome of both infection and immunity.

PMID- 11535343
TI  - Induction of cytokine mRNA in peripheral blood mononuclear cells of infants after
      the first dose of measles vaccine.
AB  - To better characterize the cytokine response to measles virus vaccine, we
      examined the levels of IL-2, IL-4, IL-5, IL-10, IL-12 and gamma-interferon (gamma
      IFN) in measles virus-stimulated peripheral blood mononuclear cells from 18
      donors before and 2 weeks after vaccination. Donors were grouped as seropositive
      or seronegative on the basis of measles-specific IgM antibody present at 2 weeks
      postvaccination. After vaccination, similar levels of upregulation of IL-2 and
      gamma-IFN mRNA were observed in the two groups. The majority of donors in both
      groups did not exhibit an increase in measles specific IL-4 or IL-10 mRNA after
      vaccination. IL-12 mRNA was not induced by measles virus in any of the donors. A
      statistically significant upregulation of IL-5 mRNA was observed among
      seropositive (9/13) compared with seronegative (1/5) donors after vaccination
      (P=0.09, one tailed Fisher's test). The observed measles specific induction of IL
      5 mRNA is suggestive of a possible association between IL-5 production and an
      antibody response to measles virus.

PMID- 11535344
TI  - Anterior lateral ankle ligament damage and anterior talocrural-joint laxity: an
      overview of the in vitro reports in literature.
AB  - OBJECTIVE: To provide a clear overview of the literature on the relationship
      between increased lateral ankle ligament damage and anterior talocrural-joint
      laxity. DESIGN: A systematic review of the literature. BACKGROUND: Diagnostic
      methods for inversion injuries of the ankle have remained controversial
      throughout the years. An instrumented test for anterior talocrural-joint laxity
      could be a diagnostic tool for evaluation of anterior lateral ankle ligament
      function. METHODS: An advanced electronic database search using MEDLINE and
      EMBASE was performed to find studies describing the correlation between lateral
      ankle ligament damage and talocrural-joint laxity. Two reviewers assessed the
      methodological quality for each study and agreement was noted. Two reviewers
      extracted all relevant data with respect to methodology, motion constraints and
      laxity measurement. RESULTS: The quality assessment resulted in 5 studies being
      scored as high quality and 5 as low quality. Different test devices were used to
      apply the load and measure the displacement. All in vitro tests applied a load to
      the calcaneus and subsequently measured the translation of the talus and/or
      calcaneus relative to the tibial dome. Rotation in the transversal and frontal
      plane was restricted in 8 tests. After analysis of the results presented by nine
      different studies, the mean value of anterior talocrural-joint laxity with intact
      ligaments is 4.2 mm. After sectioning of the anterior talofibular ligament, the
      mean anterior laxity value is 6.5 mm. The mean anterior laxity value after
      sectioning of the calcaneofibular ligament increases to 8.4 mm. The mean anterior
      laxity value with the foot in dorsal flexion (3.1 mm) is less than the mean value
      with the foot in neutral position (4.5 mm) or in plantar flexion (4.7 mm). The
      applied load and the anterior laxity values between the different studies vary
      greatly. CONCLUSIONS: Each ligament section results in significantly increased
      talocrural-joint laxity. Talocrural-joint laxity can be used as a measure for
      damage to the anterior talofibular ligament and/or the calcaneofibular ligament.
      From this review, it is neither possible to give universal recommendations about
      the optimal flexion angle for testing talocrural-joint laxity as a measure for
      lateral ankle ligament function, nor to recommend the ideal load for performing
      the test. RELEVANCE: The development of an instrumented test as a diagnostic tool
      for anterior talocrural-joint laxity in the clinical setting is near at hand and
      practicable.

PMID- 11535345
TI  - Influence of femoral anteversion on proximal femoral loading: measurement and
      simulation in four patients.
AB  - OBJECTIVE: The aim of this study was to determine the loading of the proximal
      femur during daily activities and to quantify the influence of femoral
      anteversion. DESIGN: This study combined experimental and analytical approaches
      to determine the in vivo loading at the hip joint. A numerical musculo-skeletal
      model was validated against measured in vivo hip contact forces and then used to
      analyse the influence of anteversion on the loading conditions in the femur.
      BACKGROUND: Musculo-skeletal loading of long bones is essential for joint
      replacement and fracture healing. Although joint contact forces have previously
      been measured in selected patients, the interaction between femoral anteversion
      and the associated musculo-skeletal loading environment remains unknown. METHODS:
      The gait of four patients with force measuring hip prostheses was analysed during
      walking and stair-climbing. Musculo-skeletal loading was determined using
      individual numerical models by minimising the sum of the muscle forces. RESULTS:
      Experimentally and numerically determined hip contact forces agreed both
      qualitatively and quantitatively. Muscle activity resulted in compression of the
      femur and small shear forces in the meta- and epi-physeal regions. Increasing the
      anteversion to an angle of 30 degrees increased hip contact forces and bending
      moments up to 28%. CONCLUSIONS: This study has shown that femoral anteversion has
      a strong influence on the musculo-skeletal loading environment in the proximal
      femur. RELEVANCE: Detailed musculo-skeletal modelling may allow pre-surgical,
      patient specific optimisation of loading on implant, bone and soft tissues.

PMID- 11535346
TI  - Trunk posture and spinal stability.
AB  - OBJECTIVE: The influence of trunk posture on musculoskeletal stability of the
      spine was investigated. DESIGN: A biomechanical model was developed to evaluate
      the influence of posture on spinal stability. Model performance was assessed by
      comparing predicted muscle recruitment patterns with measured EMG activity from
      the trunk muscles during static lifting exertions. METHOD: An inverted double
      pendulum model of the spine controlled by 12 muscle equivalents of the trunk was
      implemented to determine spinal load and stability. Model input included trunk
      posture and lifted mass, output included muscle recruitment patterns necessary to
      achieve stability of the spine and spinal load. EMG activity recorded from the
      trunk muscles of 10 subjects were recorded during static exertions in various
      trunk flexion and asymmetric postures to compare with model output. Stable spinal
      load was examined as a function of trunk flexion and asymmetry during the lifting
      exertions. RESULTS: Antagonistic co-contraction was necessary to achieve spinal
      stability, particularly in upright postures. Stable spinal load was increased in
      asymmetric postures as a result of antagonistic muscle recruitment, suggesting
      greater neuromuscular control is necessary to maintain stability in asymmetric
      lifting postures. As trunk flexion angle increased, stability improved but spinal
      load was greater. CONCLUSIONS: Results illustrate that muscle recruitment
      patterns are more accurately explained by stability than by equilibrium alone.
      Spinal stability is influenced by posture. Specifically, control of spinal
      stability is reduced in asymmetric postures associated with low-back disorder
      risk. RELEVANCE: Traditional assessment of low-back disorder risk have focussed
      on spinal loading. Results illustrate that postural risk factors for low-back
      pain may be partially attributable to stability considerations.

PMID- 11535347
TI  - Functional and biomechanical assessment of the normal and rheumatoid hand.
AB  - OBJECTIVE: To assess hand function in accordance with its accepted definition and
      to compare the results of three different assessment techniques. DESIGN: A
      clinical-type assessment was used together with measurement of pinch grip and
      three-dimensional biomechanical trials. BACKGROUND: Traditional clinical
      assessment may not relate to a patient's actual hand function. If hand function
      is defined as "the ability to use the hand in daily activities" then it is more
      appropriate to measure the forces available for performing everyday tasks using
      biomechanical tests. METHODS: Eight female patients with rheumatoid arthritis and
      eight control subjects were recruited for the study. Volunteers underwent a
      clinical-type assessment using a six-task activity board. Lateral pinch grip of
      both hands was measured using a custom-built transducer. Biomechanical trials
      were conducted using a 6 degree-of-freedom transducer and 6-camera motion
      analysis. RESULTS: Functional differences between the two subject groups were
      apparent using all three methods of assessment. Pinch strength correlated well
      with the biomechanical trial data but results from the clinical-type assessment
      provided only a weak correlation. CONCLUSIONS: Clinical-type assessments do not
      give an accurate measure of hand function. Pinch strength measurements can
      provide a cost-effective alternative to full biomechanical analysis. RELEVANCE:
      Traditional functional assessment uses measurements of grip or pinch strength and
      range of motion together with a subjective assessment of activities of daily
      living. This study demonstrates that pinch strength measurements can provide an
      accurate measure of hand function. The results from activity-board trials do not
      reflect hand ability and are of limited use for hand evaluation.

PMID- 11535348
TI  - A comparison of overground and treadmill running for measuring the three
      dimensional kinematics of the lumbo-pelvic-hip complex.
AB  - OBJECTIVE: To compare overground and treadmill running for differences in the
      three-dimensional angular kinematics of the lumbo-pelvic-hip complex. DESIGN: A
      within-subject repeated measures design. BACKGROUND: The treadmill is an
      attractive research instrument as speed and slope are easily controlled and the
      required calibration volume is reduced. However, the degree to which treadmill
      running simulates overground running has not been resolved in the literature to
      date. METHODS: 10 able-bodied subjects ran overground and on a treadmill at a
      self-selected speed. The treadmill speed was matched to each subjects respective
      average overground speed. The time-distance and the three-dimensional angular
      kinematic data were captured using a passive marker based motion analysis system.
      A set of angular and temporal kinematic parameters were extracted from the data
      and subjected to statistical analyses. RESULTS: Significant differences were
      found between overground and treadmill running for all the time-distance
      parameters. Despite this, the kinematics of the lumbar spine and pelvis were
      similar between the two running conditions, with only three parameters being
      significantly different. These were lumbar extension at initial contact, anterior
      pelvic tilt at initial contact and the first maximum anterior pelvic tilt. Hip
      flexion-extension parameters were also only found to display subtle differences.
      Of the 17 hip parameters analysed, only hip flexion at initial contact, maximum
      hip flexion at loading response, hip extension at toe off, maximum hip extension
      and hip flexion-extension range of motion were found to be significantly
      different. CONCLUSION: A high powered treadmill with a minimal belt speed
      fluctuation is capable of being used to obtain a representation of the typical
      three-dimensional kinematic pattern of the lumbo-pelvic-hip complex during
      running. RELEVANCE: In order for the treadmill to be accepted as a useful
      research and/or clinical assessment instrument, it must be demonstrated that it
      does not significantly alter the performance of the evaluated activity. In this
      respect, a treadmill with minimal intra-stride belt speed variability and similar
      surface stiffness to the relevant overground condition is likely to be capable of
      being used to obtain a representation of the typical human running action for
      well accommodated subjects.

PMID- 11535349
TI  - The effect of voluntary toe-walking on body propulsion.
AB  - OBJECTIVE: We studied the kinetics of toe-walking by comparing the linear power
      flow from the leg to the upper-body. Our hypothesis was that toe-walking has no
      inherent biomechanical disadvantage with regard to upper-body propulsion and
      support. DESIGN: We studied healthy subjects capable of both heel-toe gait and
      voluntary toe-walking so that the two forms of gait could be directly compared.
      BACKGROUND: Ankle joint power at terminal stance is significantly reduced in toe
      walking, which has been presumed to imply impaired propulsion and support.
      However, linear power analysis may be more appropriate for assessing this aspect
      of gait. METHODS: We compared the normal heel-toe gait of 10 healthy young adult
      subjects to their voluntary toe-walking gait using gait laboratory kinematic and
      kinetic data. Inverse dynamic analysis was performed to determine the net joint
      moments and joint linear powers. The contribution of each joint moment to the
      total hip linear power was also determined. RESULTS: Hip linear power for toe
      walking was similar to that of heel-toe gait with no significant differences in
      the linear power peaks. The stance phase contributions of the knee and ankle
      moments were significantly altered in toe-walking only in early stance.
      CONCLUSIONS: Toe-walking does not inherently impair propulsion and support.
      RELEVANCE: Linear power analysis is a useful adjunct to clinical gait analysis,
      complementing joint power analysis. Understanding the inherent kinetics of toe
      walking will enhance our analysis of pathological toe-walking and improve
      treatment design.

PMID- 11535350
TI  - Functional roles of ankle and hip sagittal muscle moments in able-bodied gait.
AB  - OBJECTIVE: The main objectives of this study on able-bodied gait were (a) to
      identify the main functions of the ankle and hip muscle moments and their
      contribution to support and propulsion tasks, and (b) to illustrate the
      interaction between the ankle and hip moment activities. DESIGN: Twenty young,
      able-bodied male subjects walked along a 13 m path at a freely chosen speed.
      BACKGROUND: Functional contributions of the ankle and hip muscles and their
      interactions in achieving support and propulsion tasks during gait are still
      subject to controversy. METHODS: Principal component analysis was applied as a
      curve structure detection method to identify the main functional characteristics
      of the ankle and hip muscle moments. The first two principal components which
      contained over 70% and 85%, respectively, of the information in the ankle and hip
      moment curves revealed their functional tasks. Ankle versus hip moment plots was
      used to illustrate the interactions between muscles acting at the hip and ankle
      in the sagittal plane. Correlation coefficient and covariance calculations
      quantified the interaction between the ankle and hip moments. RESULTS: The first
      principal component revealed that the main role of the ankle and hip is to keep
      the body from collapsing. The second principal component is associated with the
      functional contribution of both ankle plantarflexors and hip flexors during the
      propulsion phase (50-60% of the gait cycle). High coordination (r=0.82) between
      the ankle and hip moments was observed. CONCLUSION: Maintaining body support
      against gravity was identified as the first functional task of the ankle
      plantarflexors and hip extensors, while contribution to propulsion was recognised
      as the second major role for the ankle plantarflexors and hip flexors. RELEVANCE:
      Identifying the main roles of the muscles acting at the hip and ankle during able
      bodied walking provides better insight into how pathological gait should be
      evaluated.

PMID- 11535351
TI  - Gliding resistance after repair of partially lacerated human flexor digitorum
      profundus tendon in vitro.
AB  - OBJECTIVE: This study reports the gliding resistance between repaired, partially
      lacerated tendon and pulley in human cadaver digits, using several commonly
      employed repair techniques. BACKGROUND: Suture techniques with multi-strands and
      locking loops have been recommended to reduce the risk of rupture of the repair
      tendon with early active motion. Such sutures may increase the gliding
      resistance, and the gliding resistance after tendon repair is also an important
      factor influencing the rehabilitation. METHOD: 105 specimens of second, third, or
      fourth fingers from 36 adult human hands were tested for the gliding resistance
      between flexor digitorum profundus tendon and A2 pulley in the normal condition.
      After an 80% laceration, each tendon was repaired with one of the following
      suture techniques: (1) Kessler; (2) modified Kessler; (3) Savage; (4) Lee; (5)
      Tsuge; and (6) Becker. All suture techniques were reinforced with a
      circumferential epitenon simple running suture. After tendon repair, the gliding
      resistance was remeasured. RESULTS: The gliding resistance of the Becker repair
      was significantly greater than each of the other four repairs (P<0.05). The
      resistance of the modified Kessler repair was significantly less than that of the
      Kessler, Savage, or Tsuge repairs. CONCLUSIONS: We conclude that the type of
      tendon repair can significantly affect the gliding resistance between the tendon
      and pulley system after tendon repair. RELEVANCE: The design of the tendon
      repair, through its effect on friction, may have an adverse effect on the
      clinical results of tendon mobilization.

PMID- 11535352
TI  - Biomechanical comparison of different fixations of femur-interlocking-nails.
AB  - OBJECTIVE: A new design of intra-medullary nailing fixation is investigated in
      this study. The strength properties of the new design are compared to the
      standard fixation method. DESIGN: The bone-implant-compound is examined by using
      experimental methods. BACKGROUND: Failure of bone substance in the region of the
      interlocking screws is a complication in particular in treating fractures of
      osteoporotic bone. A new additional implant is investigated, which should improve
      the fracture fixation of the bone-implant-compound. METHODS: The experiments were
      performed by using an universal testing machine. The bone-implant-compound was
      loaded by different compressive forces and the stiffness of the bone-implant
      compound was measured. The maximum force to failure was also determined by a
      destructive test. RESULTS: The experimental results indicate that the additional
      implant increases the stiffness of the bone-implant-compound. The highest stress
      concentrations occur at the drill holes of the interlocking screws. Failure of
      the bone-implant-compound occurs at higher maximum forces by using the additional
      implant. CONCLUSIONS: The additional implant improves the strength of the bone
      implant-compound. In the case of osteoporotic bone, the use of the additional
      implant is recommended. RELEVANCE: In surgical treatment of fractured femurs, the
      fracture is bridged by a medullary nail fixed with interlocking screws. Failure
      of bone substance in the region of the interlocking screws is the most common
      complication in the treatment of osteporotic bone. With the aim of preventing
      this complication, a new additional implant is developed and investigated.

PMID- 11535353
TI  - Geometry and mechanics of the human ankle complex and ankle prosthesis design.
AB  - The main objective of the study was to develop a model of the intact human ankle
      complex. It was also aimed at designing total ankle replacement which would
      better reproduce the physiological function of the joint. Passive flexion was
      analysed in seven lower-leg preparations with a stereophotogrammetric system. The
      articular surfaces and fibres within the calcaneofibular and tibiocalcaneal
      ligaments prescribed the changing positions of the axis of rotation. Joint motion
      included rolling as well as sliding. A computer-based model elucidated the
      observed kinematics at the intact joint. The experimental evidence and the
      geometrical model gave the basis for the design of models of replaced ankle in
      the sagittal plane. A three-component, convex-tibia prosthesis was eventually
      selected with articular surface shapes compatible with the geometry of the
      ligaments. It was demonstrated that in intact ankle joint, the geometry of the
      articular surfaces is strictly related to that of the ligaments and that current
      prosthesis designs do not restore physiological pattern of ligament tensioning.
      Careful reconstruction of the ligaments is recommended in any ankle surgery for
      maintenance of the normal kinematics and mechanics. A proposed novel design based
      on ligament/shape compatibility may improve total ankle replacement results.

PMID- 11535354
TI  - Effect of errors in the identification of anatomical landmarks on the accuracy of
      Q angle values.
AB  - OBJECTIVE: To determine the effect of error in the location of the anterior
      superior iliac spine, and the centres of the patella and tibial tuberosity, on
      the measured value of the quadriceps angle. BACKGROUND: The quadriceps angle is
      said to be relevant in the etiology and management of patello-femoral pain.
      However, the issues around measurement accuracy have not been reported. METHODS:
      Errors between 1 and 5 mm were introduced to the medial/lateral and vertical co
      ordinate data describing the position of the anterior superior iliac spine, the
      centre of the patella and the centre of the tibial tuberosity, and the effect on
      the quadriceps angle determined. RESULTS: Errors between 1 and 5 mm in the
      medial/lateral location of the centre of the patella produced changes in the
      quadriceps angle between 1.13 degrees and 5.53 degrees. Errors between 1 and 5 mm
      in the medial/lateral location of the tibial tuberosity produced changes in the
      quadriceps angle between 1.02 degrees and 5.18 degrees. CONCLUSIONS: The
      quadriceps angle is highly sensitive to error in the definition of the centre of
      the patella and tibial tuberosity. As an approximation, these centres need to be
      defined with an accuracy of less than 2 mm if the error in the quadriceps angle
      is to remain below 5 degrees. RELEVANCE: Until a clinical technique for measuring
      the quadriceps angle with a high level of accuracy is developed, the clinical use
      of the quadriceps angle is questionable.

PMID- 11535355
TI  - Quantification of first tarsometatarsal joint stiffness in hallux valgus
      patients.
AB  - OBJECTIVE: Comparison of the clinical mobility test of the first tarsometatarsal
      joint with Doppler Imaging of Vibrations measurement of the stiffness of this
      joint in hallux valgus patients. DESIGN: Clinical testing of first
      tarsometatarsal joint mobility was related to independent Doppler Imaging of
      Vibrations measurement of first tarsometatarsal joint stiffness. BACKGROUND:
      Hypermobility of the first tarsometatarsal joint has consequences for the
      surgical treatment of hallux valgus deformity. However, the clinical test is
      subjective. Doppler Imaging of Vibrations could be helpful in quantification of
      the stiffness of this joint. METHODS: Clinical examination of the mobility of 32
      first tarsometatarsal joints in 20 hallux valgus patients was compared with
      Doppler Imaging of Vibrations stiffness measurements performed by an independent
      observer. RESULTS: There was a statistically significant relation between the
      clinical test and the stiffness measurement by Doppler Imaging of Vibrations.
      CONCLUSION: Doppler Imaging of Vibrations proves to be a method to quantify first
      tarsometatarsal joint stiffness and could contribute to a rational policy for the
      surgical treatment of hallux valgus deformity. RELEVANCE: The clinical test to
      establish hypermobility of the first tarsometatarsal joint is subjective. Doppler
      Imaging of Vibrations offers objective criteria and quantification of first
      tarsometatarsal joint stiffness. This provides additional information for the
      choice of the surgical procedure to correct hallux valgus deformity.

PMID- 11535356
TI  - Anti-inflammatory and analgesic properties of the stem bark extracts of
      Erythrophleum suaveolens (Caesalpiniaceae), Guillemin & Perrottet.
AB  - The MeOH stem bark extract of Erythrophleum suaveolens dissolved in water and
      shaken up with ethylacetate (EtOAc) and fractionated on a polyamide column with
      methanol as eluent produced five principal fractions. These fractions were
      designated as fraction A (74.8 mg yield and rich in alkaloids), fraction B (36.6
      mg), fraction C (7.8 mg yield, monomeric procyanidin), fraction D (26.6 mg yield,
      rich in monomeric and oligomeric procyanidin), and fraction E (18.1 mg yield,
      rich in polymeric procyanidin). The original MeOH extract administered (100 mg/kg
      po) produced about 47% inhibition of carrageenin-induced paw oedema 1 h after
      administration. Fraction D, obtained from the ethylacetate extract and rich in
      procyanidins produced over 33% inhibition of carrageenan-induced paw oedema while
      a dose of 19.2 microg/ml produced 100% inhibitory effect on 5-lipoxygenase. A
      dose of 100 mg/kg of the MeOH extract also produced over 30% reduction of the
      sensitivity to pain while 50 mg/kg of fraction D rich in procyanidins produced
      over 45% analgesic effects. These results were judged significant compared to
      those obtained with indomethacin and acetylsalicylic acid. These findings suggest
      that extracts of the bark of Erythrophleum suaveolens possess potent anti
      inflammatory and analgesic property and that the procyanidins lead to the
      observable pharmacological effects.

PMID- 11535357
TI  - The central nervous effects of Mitragyna africanus (Willd) stembark extract in
      rats.
AB  - The acute toxicity and the central effects of Mitragyna africanus (M. africanus)
      stembark methanol extract were studied in rats. The extract did not produce any
      death in the treated rats even at the highest dose (6400 mg kg(-1)) used. It
      produced depressant effects on the central nervous system. The stembark extract
      potentiated amylobarbitone sleeping time in rats dose-dependently, induced sleep
      in rats and also produced significant local anaesthetic effect on rabbits, the
      effects being comparable to that of xylocaine. The extract protected rats treated
      with a convulsive dose of strychnine (2 mg kg(-1)) and increased the period of
      onset of convulsions and decreased the number of spasms.

PMID- 11535358
TI  - Antibacterial activity of traditional Australian medicinal plants.
AB  - Fifty-six ethanolic extracts of various parts of 39 plants used in traditional
      Australian Aboriginal medicine were investigated for their antibacterial
      activities against four Gram-positive (Bacillus cereus, Enterococcus faecalis,
      Staphylococcus aureus and Streptococcus pyogenes) and four Gram-negative
      (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Salmonella
      typhimurium) bacterial species. In a plate-hole diffusion assay, 12 extracts
      inhibited the growth of one or more of the bacteria, with five extracts showing
      broad spectrum antibacterial activity against Gram-positive bacteria. B. cereus
      was the most susceptible bacterium, with all 12 extracts displaying activity
      against this organism. Extracts from the leaves of Eremophila species
      (Myoporaceae) were the most active, with Eremophila duttonii exhibiting the
      greatest activity (against Gram-positive bacteria). The antibacterial effects of
      E. duttonii were further investigated by time-course growth assays which showed
      that significant growth inhibition was observed in cultures incubated in the
      presence of the extract within 1 h for B. cereus, E. faecalis and S. aureus and 2
      h for S. pyogenes.

PMID- 11535359
TI  - Subacute toxicity evaluation of a hydroalcoholic extract of Pterodon pubescens
      seeds in mice with collagen-induced arthritis.
AB  - When the immune system is stimulated there is a concomitant decrease in drug
      biotransformation and elimination that may results in unwanted drug response and
      toxic side effects. We investigated the subacute toxicity of a hydroalcoholic
      extract of Pterodon pubescens seeds (HEPp) to DBA1/J mice with collagen II
      induced arthritis. The oral treatment with HEPp reduced the arthritic index
      without any concomitant alteration in their hematological examination,
      histopathological analysis and relative or absolute weight of several organs and
      in several clinical biochemical parameters when compared with the control group.
      We concluded that daily administration of anti-arthritic doses of HEPp did not
      induce any detectable subacute toxic side-effect in mice whose host defense
      mechanisms is active as we can observe in mice with CIA.

PMID- 11535360
TI  - Cardiovascular and diuretic activity of kaurene derivatives of Xylopia aethiopica
      and Alepidea amatymbica.
AB  - The extractives, crude and pure, of Alepidea amatymbica (AA) and Xylopia
      aethiopica (XA) were subjected to bioassay-directed phytochemical examination for
      potential cardiovascular and diuretic activity. All extractives and derivatives
      (XA/O, AA/1, xylopic acid, AA/3, AA/4, AA/5, AA/6, XA/1, XA/2, XA/3) displayed
      low toxicity, with LC(50) 0.5-5.0 ng/ml. For the first time, diterpene kaurenoids
      were reported to have significant systemic hypotensive and coronary vasodilatory
      effect accompanied with bradycardia. These effects were attributed to calcium
      antagonistic mechanism. The diuretic and natriuretic effects found were similar
      to the effects of chlorothiazide, suggesting inhibition of Na+ and K+
      reabsorption in the early portion of the distal tubule. Further experiments are
      needed to elaborate the exact mechanisms of the hypotensive and diuretic effects
      of diterpene kaurenoids.

PMID- 11535361
TI  - Ethnobotanical survey of medicinal plants used for the treatment of diabetes,
      cardiac and renal diseases in the North centre region of Morocco (Fez-Boulemane).
AB  - In order to make an inventory of herbal remedies commonly used in the treatment
      of diabetes, hypertension and renal diseases in the North centre region of
      Morocco, 1527 patients (1095 diabetic patients, 274 with renal disorders and 158
      with cardiac disorders) and 25 traditional herbal healers were interviewed in
      four different areas of Fez-Boulemane region. More than 1153 of the total
      patients interviewed (76%) used regularly medicinal plants to treat diabetes,
      cardiac and renal diseases. These data showed that phytotherapy has always be
      practiced in this region. All the persons interviewed have indicated that the
      reasons of using phytotherapy is that the plant medicines are cheapest (54%) and
      more efficient (38%) than modern medicine. They also reported that the result of
      phytotherapy is better (72%). Our survey started at May 1997. About 90 plants
      were cited (54 plants for diabetes, 11 for cardiac diseases, 19 for hypertension
      and 33 for renal diseases). The plants reported have been identified and are
      presented in a table with the vernacular name, useful parts, ecological
      distribution and medicinal uses. Only 12% of the total patients have a relative
      knowledge of the toxic plants. The result indicated that nine plants are
      extremely toxic at high doses and chronic treatment. Fifty nine percent of the
      interviewers have indicated that they used medicinal plants from the experience
      of the other.

PMID- 11535362
TI  - Cytoprotective effect of Scutellaria baicalensis in CA1 hippocampal neurons of
      rats after global cerebral ischemia.
AB  - Based on the use of Scutellaria baicalensis for the treatment of stroke in
      traditional Oriental medicine, the current study was carried out to evaluate
      neuroprotective effects of S. baicalensis after transient global ischemia using
      rat 4-vessel occlusion model. Methanol extracts from the dried roots of S.
      baicalensis (0.1-10 mg/kg) administered intra-peritoneally significantly
      protected CA1 neurons against 10 min transient forebrain ischemia as demonstrated
      by measuring the density of neuronal cells stained with Cresyl violet. Methanol
      extract of S. baicalensis inhibited microglial tumor necrosis factor-alpha (TNF
      alpha) and nitric oxide production, and protected PC12 cells from hydrogen
      peroxide-induced toxicity in vitro.

PMID- 11535363
TI  - Antiviral and antimicrobial activities of Colombian medicinal plants.
AB  - Strong antiviral and antimicrobial activities were detected in methanolic
      extracts of 24 plants used medicinally in the treatment of skin infections in
      four different regions of Colombia. Thirteen extracts displayed activity against
      herpes simplex virus (HSV) whereas none was active against poliovirus. The
      antiviral activity was indicated by a total inhibition of viral cytopathic
      effects (CPE) at a non-cytotoxic concentration of the extract. The most potent
      extract was obtained from Byrsonima verbascifolia (L.) HBK. which showed anti-HSV
      activity at a concentration as low as 2.5 microg/ml. Antimicrobial screening was
      conducted using the disc diffusion assay against Klebsiella pneumoniae,
      Escherichia coli, Streptococcus faecalis, Mycobacterium phlei, Bacillus subtilis,
      Staphylococcus aureus, Pseudomonas aeruginosa, Salmonella typhimurium and the
      human pathogenic yeast, Candida albicans. Anti-Candida activity was observed for
      Piper lanceaefolium HBK. and Juglans neotropica Diels. Twenty-two extracts
      displayed activity against Gram-positive bacteria whereas none was active against
      the Gram-negative species. We concluded that these Colombian medicinal plants
      represent an untapped source of potentially useful antivirals and are worthy of
      further study.

PMID- 11535364
TI  - Anti-inflammatory activity of methanol extract of Kalopanax pictus bark and its
      fractions.
AB  - The methanol extract of Kalopanax pictus bark was evaluated on anti-inflammatory
      and anti-nociceptive activities in animal models. The extract produced a
      significant inhibition of vascular permeability at doses of 1 and 3 g/kg, p.o. in
      mice and of leucocyte emigration at doses of 0.15 and 0.3 g/rat, s.c., in CMC
      pouch of rats. However, the extract (0.25 and 3 g/kg, p.o.) did not show anti
      inflammatory activity in carrageenan induced edema of rats. The extract at a dose
      of 2.5 g/kg, p.o. inhibited writhing syndromes, whereas it did not exhibit anti
      nociceptive in Randall-Selitto assay. The methanol extract was then partitioned
      with n-hexane, chloroform, ethyl acetate and butanol to give each soluble
      fraction and finally water soluble fraction. Among those fractions, the
      inhibitory effect on vascular permeability in mice was produced by ethyl acetate
      soluble fraction in this activity-guided fractionation. The methanol extract
      showed low acute toxicity in mice. These results suggest that the methanol
      extract of Kalopanax pictus bark has an anti-inflammatory activity which is
      distributed in the ethyl acetate fraction.

PMID- 11535365
TI  - Preventive effect of Coriandrum sativum (Chinese parsley) on localized lead
      deposition in ICR mice.
AB  - The preventive effect of Coriandrum sativum, Fam. UMBELLIFERAE (Chinese parsley)
      on lead deposition was investigated in male ICR mice given lead (1000 ppm) as
      lead acetate trihydrate in drinking water for 32 days. Administration of Chinese
      parsley to mice by gastric intubation was performed for 25 days from day 7 after
      the start of lead exposure up to the end of the experiment. The mice were then
      sacrificed for comparison of lead distribution. The lead reached its highest
      concentration in the femur but localized lead deposition in the femur was
      significantly decreased by meso-2,3-dimercaptosuccinic acid (DMSA), a chelating
      agent used as a positive control to validate this experimental model.
      Administration of Chinese parsley also significantly decreased lead deposition in
      the femur and severe lead-induced injury in the kidneys. In addition, urinary
      excretion of delta-aminolevulinic acid (ALA) which is known to increase with lead
      intake was significantly decreased after administration of Chinese parsley. The
      MeOH extract of Chinese parsley also reduced lead-induced inhibition of delta
      aminolevulinic acid dehydratase (ALAD) activity in vitro. These results suggest
      that Chinese parsley has suppressive activity on lead deposition, probably
      resulting from the chelation of lead by some substances contained in Chinese
      parsley.

PMID- 11535366
TI  - Screening of Chinese herbal drug extracts for inhibitory activity on nitric oxide
      production and identification of an active compound of Zanthoxylum bungeanum.
AB  - Sixty-eight water and methanol extracts from 34 Chinese herbal drugs, most of
      which are used for inflammatory diseases, were screened for their inhibitory
      effects on nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated
      J774.1 macrophages and in LPS/interferon (IFN)-gamma-stimulated mouse peritoneal
      exudate macrophages. Among the extracts, methanol extracts of Myristica fragrans,
      Plantago asiatica, Rubia cordifolia, and Zanthoxylum bungeanum showed significant
      inhibition in J774.1 macrophages, while in mouse peritoneal exudate macrophages,
      water extracts of Ru. cordifolia and Scutellaria baicalensis and methanol
      extracts of Angelica megaphylla, My. fragrans, and Z. bungeanum inhibited the NO
      production. Among them, inhibition of water extract of Sc. baicalensis was found
      to be mainly due to direct scavenging of NO radicals, through an examination of
      its scavenging activity on PAPA NONOate-generated NO radicals, while water
      extract of Ru. cordifolia and methanol extracts of An. megaphylla, My. fragrans,
      P. asiatica, and Z. bungeanum showed inhibition on iNOS mRNA expression. At last,
      an inhibitory compound on iNOS mRNA expression was isolated from a methanol
      extract of Z. bungeanum and identified as 4-O-beta-D-glucopyranosyldihydroferulic
      acid by NMR spectral analyses and chemical synthesis.

PMID- 11535367
TI  - Effects of Buddleja globosa leaf and its constituents relevant to wound healing.
AB  - An aqueous extract of Buddleja globosa leaves, used traditionally in Chile for
      wound healing, was tested for the ability to stimulate growth of fibroblasts in
      vitro and for antioxidant activity in the same fibroblast cell system challenged
      with hydrogen peroxide. Low concentrations of the extract gave an increase in
      fibroblast growth which was not statistically significant but cytotoxicity was
      observed at concentrations greater than 50 microg/ml. The extract showed strong
      antioxidant effect and fractionation led to the isolation of three flavonoids and
      two caffeic acid derivatives, each of which was shown to contribute to the
      antioxidant effect at concentrations below 10 microg/ml. These activities would
      accelerate the healing of wounds.

PMID- 11535368
TI  - Effect of silibinin and vitamin E on restoration of cellular immune response
      after partial hepatectomy.
AB  - Our aim was to study the antioxidant and immunomodulatory effect of silibinin and
      vitamin E on the early postoperative course in rats that had undergone a partial
      hepatectomy (PHX). Male Wistar rats that were treated with silibinin (50
      mg/b.w.kg i.p.) and/or vitamin E (500 mg/b.w.kg p.o.) were randomised to undergo
      70% PHX. At 72 h after operation, Concanavalin A (Con-A) induced lymphocyte
      proliferation, and lipopolysaccharide (LPS) induced interleukin-1 (IL-1)
      mitogenicity and tumour necrosis factor-alpha (TNF-alpha) cytotoxicity were
      measured in the spleen. In addition, total free radical scavenger capacity of the
      liver was analysed. In PHX animals, Con-A induced lymphocyte proliferation was
      significantly decreased, and both LPS induced IL-1 and TNF-alpha activity were
      significantly increased as compared to Sham treated animals. Treatment with
      silibinin and vitamin E synergistically restored both lymphocyte proliferation
      (P<0.01) and cytokine activity (P<0.001) in PHX animals. In addition, silibinin
      and vitamin E synergistically (P<0.001) restored total hepatic free radical
      scavenger capacity as well as serum levels of AST and gammaGT, that were all
      markedly decreased in PHX animals. Our results suggest that preoperative
      treatment with silibinin and/or vitamin E modulates the cellular immunoresponse
      and restores impaired liver function following PHX, presumably through their
      antioxidant capacity. This may explain their beneficial effects on the
      postoperative course of liver repair.

PMID- 11535369
TI  - Ameliorative effects of Anoectochilus formosanus extract on osteopenia in
      ovariectomized rats.
AB  - The purpose of this study was to determine ameliorative effects of crude aqueous
      extract of Anoectochilus formosanus (AFE) on osteopenia in ovariectomized (OVX)
      rats. First, all of the rats were divided into sham and OVX groups. The OVX rats
      were allowed to lose bone for 6 weeks. At 6 weeks post-OVX, the OVX rats were
      divided into four groups treated with water, 17beta-estradiol (30 microg/kg,
      daily s.c. injection) or AFE (0.5, 2 g/kg, daily, orally) for 12 weeks. In OVX
      rats, the increases of body weight and serum total cholesterol were significantly
      decreased by AFE or 17beta-estradiol treatment. In OVX rats, atrophy of uterus
      and vagina was preserved by treatment with 17beta-estradiol, but not by AFE. The
      decreased weight of pituitary was increased by treatment with both 17beta
      estradiol and AFE. There were decreases in bone density and calcium content
      including the right femur and the fourth lumbar vertebra, when compared with the
      sham control rats. Treatment with either 17beta-estradiol or AFE ameliorated
      these changes induced by OVX. In addition, ovariectomy increased serum alkaline
      phosphatase levels. The increases were suppressed by the treatment with 17beta
      estradiol and AFE. Our results demonstrated that AEF could ameliorate ovariectomy
      induced osteopenia.

PMID- 11535370
TI  - Investigation of some Hypericum species native to Southern of Brazil for
      antiviral activity.
AB  - Three plant species, Hypericum connatum, Hypericum caprifoliatum, Hypericum
      polyanthemum (Guttiferae), growing in Southern of Brazil were chemically
      investigated and tested for their antiviral activity against feline
      immunodeficiency virus (FIV). The chemical analysis revealed the presence of
      polyphenolic compounds such as tannins and flavonoids. Hypericin was not detected
      in these species. The aqueous extract (AE), the aqueous extract with low tannin
      concentration (LTCAE) and the methanolic extract (ME) were tested for their
      cytotoxic properties in concentrations of 50-150 microg/ml. AE was toxic to CRFK
      for the three species in all concentrations. LTCAE and ME varied between
      different concentrations being not toxic or allowing 80% of cell growth. LTCAE
      and ME (10-50 microg/ml) were analyzed for antiviral activity by inhibition of
      CPE and measuring FIV genome from cell culture supernatant. LTCAE of all species
      in this work did not cause any inhibition of FIV. Although no difference was seen
      in CPE, a lower number of viral particles in the supernatant was observed when
      FIV infected cells were treated with ME of H. connatum. These results suggest
      that some plants of the genus Hypericum from Southern Brazil contain compounds
      with potential antiviral activity against lentiviruses.

PMID- 11535371
TI  - The effects of storage on the biological activity of medicinal plants from Nepal.
AB  - The in vitro biological activity of 19 medicinal plants from Nepal was re
      assessed after 6 years of storage. Methanol extracts from the plants were assayed
      for activity against six strains of bacteria and three strains of fungi. The
      extracts were tested with and without exposure to UV light in order to identify
      photoactivity. Out of the 19 plants tested, three lost all activity, six retained
      all activity, and ten had partial activity. The results will be of interest to
      traditional healers in Nepal, and may impact the sustainable harvesting of these
      medicinal plants.

PMID- 11535372
TI  - Immunomodulatory activity of Chilean Cyttaria species in mice with L5178Y
      lymphoma.
AB  - The immunomodulatory effect of hydrosoluble extracts of four Chilean Cyttaria
      species (Discomycetes, Fungi) was assessed in mice with L5178Y lymphoma. Oral
      administration of 100 mg extract per day for 7 days enhanced the percentual
      phagocytosis and phagocytosis index in animals receiving Cyttaria berteroi,
      Cyttaria darwinii, Cyttaria espinosae and Cyttaria harioti extracts. Differences
      in the digestion index were observed in mice treated with C. darwinii and C.
      berteroi. In the delayed-type hypersensitivity model, only C. harioti was able to
      modify the immune response. The results suggest that intake of Cyttaria can
      improve the immune system of consumers.

PMID- 11535373
TI  - Effects of Korean red ginseng and its mixed prescription on the high molecular
      weight dextran-induced blood stasis in rats and human platelet aggregation.
AB  - This study was undertaken to evaluate the antithrombotic effects of Korean Red
      Ginseng (KRG) and its new prescription (KRGP) consisting of five herbs such as
      Korean red ginseng, Ganoderma, Cinnamomi Cortex, Glycyrrhizae Radix and
      Laminaria. In rats with blood stasis induced by high molecular weight dextran,
      KRG and KRGP significantly restored not only the number of platelets and
      fibrinogen, but also suppressed the fibrin degradation products (FDP) to normal
      range. In platelet aggregation assay with human platelet rich plasma (PRP), KRG
      and KRGP significantly inhibited thrombin and collagen-induced platelet
      aggregation. The IC(50) values of KRG and KRGP were >2 and 0.23+/-0.01 mg/ml for
      thrombin, 0.32+/-0.01 and 0.17+/-0.02 mg/ml for collagen and 0.72+/-0.25 and >2
      mg/ml for ADP, respectively. In coagulation assay, KRG and KRGP significantly
      prolonged activated partial prothrombin time (APPT) and prothrombin time (PT) as
      compared with control data. KRGP was found to be more effective than KRG alone on
      antithrombotic activity. These results suggest that KRGP may exert its
      antithrombotic activity due to inhibition of platelet aggregation and coagulation
      activity more than KRG.

PMID- 11535374
TI  - Commentary: cosmetic dermatology.

PMID- 11535375
TI  - You've come a long way baby: a history of cosmetic lead toxicity.

PMID- 11535376
TI  - Cosmetology, cosmetics, cosmeceuticals: definitions and regulations.

PMID- 11535377
TI  - The cultural and philosophical concepts of cosmetics in beauty and art through
      the medical history of mankind.

PMID- 11535378
TI  - Dry skin and moisturizers.

PMID- 11535379
TI  - Soaps, shampoos, and detergents.

PMID- 11535380
TI  - Antiperspirants and deodorants.

PMID- 11535381
TI  - Camouflage and makeup preparations.

PMID- 11535382
TI  - Cosmetics for the elderly.

PMID- 11535383
TI  - Special considerations in eye cosmetics.

PMID- 11535384
TI  - Hair care products: waving, straightening, conditioning, and coloring.

PMID- 11535386
TI  - Nail care products.

PMID- 11535385
TI  - Hair removal.

PMID- 11535387
TI  - Oral therapeutics and oral cosmetics.

PMID- 11535388
TI  - Sunscreens.

PMID- 11535389
TI  - Hydroxy acids and retinoids in cosmetics.

PMID- 11535390
TI  - Antioxidants and vitamins in cosmetics.

PMID- 11535391
TI  - Botanicals as topical agents.

PMID- 11535393
TI  - Depigmenting and bleaching agents: coping with hyperpigmentation.

PMID- 11535392
TI  - Mineral waters: instead of cosmetics or better than cosmetics?

PMID- 11535394
TI  - Percutaneous absorption and delivery systems.

PMID- 11535395
TI  - Contact dermatitis to cosmetics.

PMID- 11535396
TI  - A glance into the crystal ball: winners and losers in cosmetics.

PMID- 11535407
TI  - Multiple forms of formamidopyrimidine-DNA glycosylase produced by alternative
      splicing in Arabidopsis thaliana.
AB  - Formamidopyrimidine-DNA glycosylase (FPG) catalyzes the initial steps in the
      repair of DNA containing oxidized purines. Two cDNA clones from Arabidopsis
      thaliana encoding homologs of bacterial FPG have previously been described. We
      now report that there are at least five additional variants of FPG mRNA in
      Arabidopsis, each apparently produced from the same gene (AtMMH) by alternative
      splicing. Thus, AtMMH, like at least four other genes in the base excision repair
      pathway of human cells, produces multiple forms of protein product through
      alternative splicing. The variant forms of Arabidopsis FPG may be localized in
      different locations in the cells, may have different preferences for oxidized
      substrates, and/or may recruit different proteins that guide the subsequent steps
      of base excision repair.

PMID- 11535408
TI  - Future UV radiation in Central Europe modelled from ozone scenarios.
AB  - Photobiologically and photochemically relevant UV radiation for the time around
      the years 2015 and 2050 is estimated by radiative transfer calculations using
      variable ozone content based on model simulations. The future cloud conditions
      are assumed unchanged. Assuming various emission scenarios of
      chlorfluorohydrocarbons (CFCs) and other trace gases, and taking into account
      future temperature development and changing atmospheric dynamic conditions, ozone
      values are simulated. On the basis of these data, three different scenarios of
      the future total ozone content over Central Europe are analysed, which represent
      from current knowledge, probable as well as optimistic (high ozone and low UV
      irradiance) and pessimistic (low ozone and high UV irradiance) conditions.
      According to these scenarios the future development of the UV radiation is
      expected not to follow the increasing trend of UV irradiation observed during the
      last three decades. The predicted changes are highly variable with season. During
      late winter and spring, the enhanced recent UV values will persist for the next
      decades. Till 2015 a further slight increase is predicted for springtime. In
      contrast, during summer and fall, the UV level is assumed to remain on the recent
      level. For 2050 a decrease to values close to that of an anthropogeneous nearly
      undisturbed ozone chemistry, as it was found around 1970, is predicted. In
      addition to average long-time variations of the UV irradiance, short-time
      increase may occur due to ozone minihole events or due to a large volcanic
      eruption. The latter can produce a marked increase in UV radiation for several
      months. During ozone minihole events, with maximum occurrence in spring, UV
      irradiance is typically increased for a few days. Such episodes must be taken
      into account additionally to the average UV development. They will occur also in
      the future and result in UV radiation increases against undisturbed conditions,
      which are similar to present minihole events. These differences are much larger
      than the average changes predicted for future ozone development.

PMID- 11535409
TI  - Melanin content of cultured human melanocytes and UV-induced cytotoxicity.
AB  - Cultured melanocytes originating from persons with different skin phototypes were
      utilized for measurement of endonuclease sensitive sites induced by UVB and the
      determination of cell survival after UVA or UVB irradiation. During culture, the
      melanocytes largely maintained their phenotypic characteristics according to
      their original skin phototype. Total melanin concentrations were 4.9 times higher
      in the darker skin phototype (IV-VI) melanocytes when compared to the cells from
      lighter skin phototypes (I-III). Also phaeomelanin contents were higher (2.5
      times) in the skin phototype (IV-VI) melanocytes which implies that the cells
      from light skin types contain less melanin, but a relatively high proportion of
      phaeomelanin. After UVB irradiation a stronger induction of endonuclease
      sensitive sites was found for melanocytes with a lower level of total melanin and
      a high content of pheomelanin. By measuring the clone forming ability in
      different melanocyte cultures after UVB irradiation, significant better survival
      was found in case of the cells with the higher melanin content. Despite the large
      variations in melanin content, no significant difference in survival after UVA
      irradiation could be demonstrated in this way. Our results suggest a protective
      effect of melanin for UVB and indicate the importance of the measurements of
      melanin content and composition when different parameters of UV-induced damage
      are studied in melanin producing cells.

PMID- 11535410
TI  - Phototoxic process after rapid photosensitive membrane damage of 5,5"
      bis(aminomethyl)-2,2':5',2"-terthiophene dihydrochloride.
AB  - We report a new aspect of rapid (<30 s) light-induced cell membrane damage
      photosensitized by 5,5"-bis(aminomethyl)-2,2':5',2"-terthiophene dihydrochloride
      (BAT), which is a water-soluble alpha-terthienyl analogue, using a high-power
      laser (light intensity 1.6 W cm(-2)). In this paper, we will discuss the
      relationship between the exposure time of the cells to the photosensitizer and
      the phototoxic process. Three toxic processes can be identified: first, a non
      light-mediated toxicity dependent on BAT-cell incubation; second, a phototoxicity
      independent of BAT exposure time when the BAT concentration is in the 2-10-microM
      range; third, a phototoxicity dependent on BAT exposure time when BAT
      concentration becomes 20 microM. The cytotoxicity decreases when alpha
      tocopherol, an antioxidant, is added to a cell membrane. This pattern of
      phototoxicity is the typical of a phospholipid peroxidation chain reaction and
      oxidative damage of membrane proteins triggered by a reactive oxygen species
      generated by a triplet state of BAT. The BAT exposure time is clearly correlated
      with the partition of the photosensitizer in the cell membrane and inside the
      cell.

PMID- 11535411
TI  - Synthesis of a novel hypocrellin B derivative and its photogeneration of
      semiquinone anion radical.
AB  - In order to improve the photosensitizing activity of HB further, the complex of
      5,8-di-Br-HB with Al(3+) was first designed and synthesized in high yield. 5,8-di
      Br-HB forms a 2:1 type (metal-ligand ratio) complex with Al(3+) measured by molar
      ratio and continuous variation methods. The new photosensitizer was characterized
      by UV-Vis, IR, 1H NMR and elemental analysis measurements. Based on the above
      experimental results, we first proposed a polymer-like structural model of the
      complex. The water-solubility and red absorption of the [Al(2)(5,8-di-Br
      HB)Cl(4)](n) complex are both enhanced over hypocrellin B. In addition, the EPR
      and spectrophotometric measurements demonstrate that semiquinone anion radical of
      [Al(2)(5,8-di-Br-HB)Cl(4)](n) can be produced by [Al(2)(5,8-di-Br-HB)Cl(4)](n)
      photosensitization. The generation efficiency of ([Al(2)(5,8-di-Br
      HB)Cl(4)](n))(.-) is almost equal to that of HB(.-). These results obtained
      indicated that [Al(2)(5,8-di-Br-HB)Cl(4)](n)was at least a favorable Type I
      phototherapeutic agent.

PMID- 11535412
TI  - Attempts to measure sensitiser photophysics in opaque tissue.
AB  - Diffuse reflectance laser flash photolysis has been used in an attempt to measure
      transient triplet spectra of the sensitisers, disulphonated aluminium
      phthalocyanine and porphyrin IX (derived from 5-amino laevulinic acid), in opaque
      tissue and models. The latter consisted of tissue phantoms; the former included
      rat liver and red blood cells. In all cases, triplet-triplet absorption spectra
      with relatively poor signal-to-noise were obtained providing some encouragement
      in the application of this technique to in vivo studies on photosensitisers.

PMID- 11535414
TI  - Bispecific and bifunctional single chain recombinant antibodies.
AB  - Bispecific and bifunctional monoclonal antibodies as second generation
      monoclonals, produced by conventional chemical or somatic methods, have proved
      useful in the immunodiagnosis and immunotherapy of cancer and other diseases.
      Recombinant antibodies produced by genetic engineering techniques have also
      become available for use in preclinical and clinical studies. Furthermore,
      through genetic engineering, it is possible to remove or add on key protein
      domains in order to create designer antibody molecules with two or more desired
      functions. This review summarizes the strategies for development of single chain
      variable fragment (scFv) bifunctional and bispecific antibodies. The advantages
      and disadvantages as well as the problems of generating the various bispecific
      and bifunctional antibody constructs are reported and discussed. Since
      conventionally prepared bispecific and bifunctional monoclonal antibodies have
      already shown promise in clinical trials and results from preclinical studies of
      recombinant bispecific antibodies are encouraging, clinical trials in humans of
      recombinant bispecific and bifunctional antibodies, as a new generation of
      biologicals, are likely to be the thrust in the next decade and beyond.

PMID- 11535415
TI  - Engineering novel biocatalytic routes for production of semisynthetic opiate
      drugs.
AB  - The morphine alkaloids and their semisynthetic derivatives provide a diverse
      range of important pharmaceutical drugs. Current production of semisynthetic
      opiate drugs is by chemical means from naturally occurring morphine, codeine and
      thebaine. Although various microbial transformations of morphine alkaloids have
      been identified since the 1960s, more recently there has been considerable effort
      devoted to engineering biocatalytic routes for producing these important
      compounds. Such biocatalytic routes are attractive, as they would provide an
      alternative to the chemical production processes which suffer from limited supply
      of precursors, often low yields and toxic wastes. The biotransformation of
      morphine and codeine to the potent analgesic hydromorphone and the mild
      analgesic/antitussive hydrocodone, respectively, by recombinant Escherichia coli
      has been demonstrated and the problems encountered when engineering such a system
      will be discussed.

PMID- 11535416
TI  - Identification and characterization of Rhodopseudomonas spp., a purple, non
      sulfur bacterium from microbial mats.
AB  - A species of facultative photo-organotrophic, purple, non-sulfur bacterium was
      isolated from mixed-species microbial mats, characterized and examined for metal
      tolerance and bioremediation potential. Contributing mats were natural consortia
      of microbes, dominated by cyanobacteria and containing several species of
      bacteria arranged in a laminar structure, stabilized within a gel matrix.
      Constructed microbial mats were used for bioremediation of heavy metals and
      organic chemical pollutants. Purple, non-sulfur bacteria are characteristically
      found in lower strata of intact mats, but their contributing function in mats
      survival and function by mediating the chemical environment has not been
      explored. The gram-negative rod-shaped bacterium, reported here, produced a dark
      red culture under phototrophic conditions, reproduced by budding and formed a
      lamellar intracytoplasmic membrane (ICM) system parallel to cytoplasmic membrane,
      which contained bacteriochlorophyll a and carotenoids. This strain was found to
      have multiple metal resistances and to be effective in the reductive removal of
      Cr(VI) and the degradation of 2,4,6-trichlorophenol. Based on the results
      obtained from morphology, nutrient requirements, major bacteriochlorophyll
      content, GC content, random amplified polymorphic DNA-polymerase chain reaction
      (RAPD-PCR) profile and 16S-rDNA phylogenetic analysis, this member of the
      microbial mats may be identified as a new strain of the genus Rhodopseudomonas.

PMID- 11535417
TI  - Engineering M13 for phage display.
AB  - Phage display is achieved by fusing polypeptide libraries to phage coat proteins.
      The resulting phage particles display the polypeptides on their surfaces and they
      also contain the encoding DNA. Library members with particular functions can be
      isolated with simple selections and polypeptide sequences can be decoded from the
      encapsulated DNA. The technology's success depends on the efficiency with which
      polypeptides can be displayed on the phage surface, and significant progress has
      been made in engineering M13 bacteriophage coat proteins as improved phage
      display platforms. Functional display has been achieved with all five M13 coat
      proteins, with both N- and C-terminal fusions. Also, coat protein mutants have
      been designed and selected to improve the efficiency of heterologous protein
      display, and in the extreme case, completely artificial coat proteins have been
      evolved specifically as display platforms. These studies demonstrate that the M13
      phage coat is extremely malleable, and this property can be used to engineer the
      phage particle specifically for phage display. These improvements expand the
      utility of phage display as a powerful tool in modern biotechnology.

PMID- 11535419
TI  - Skin aging: postulated mechanisms and consequent changes in structure and
      function.
AB  - Aging is a complex process influenced by telomere shortening and damage to
      cellular DNA. New insights into age-associated decrements in DNA damage repair
      are reviewed. Age-associated gross, histologic, and functional cutaneous deficits
      are delineated. Different treatment options for aged skin are examined.

PMID- 11535420
TI  - Demographics of aging and skin disease.
AB  - What are the dermatologic needs of aging and skin disease in the elderly in the
      new millennium? This question may be impossible to answer, but predictions may be
      derived from current sources of data. Data from the US Census Bureau and the
      National Ambulatory Medical Care Survey are used to characterize current use of
      dermatologic care in the aging population of the United States and to estimate
      possible future trends in dermatologic care as the elderly population continues
      to grow. Dermatologic accompaniments of aging are briefly reviewed, as are issues
      in health care financing.

PMID- 11535421
TI  - Photoaging: pathogenesis, prevention, and treatment.
AB  - Premature skin aging, or photoaging, results largely from repeated exposure to
      ultraviolet (UV) radiation from the sun. Photoaging is characterized clinically
      by wrinkles, mottled pigmentation, rough skin, and loss of skin tone; the major
      histologic alterations lie in dermal connective tissue. In recent years, a great
      deal of research has been done to explain the mechanism by which UV induces
      dermal damage. This research has enabled the identification of rational targets
      for photoaging prevention strategies. Moreover, studies that have elucidated
      photoaging pathophysiology have produced significant evidence that topical
      tretinoin (all-trans retinoic acid), the only agent approved so far for the
      treatment of photoaging, also works to prevent it. This article summarizes
      evidence mainly from studies of human volunteers that provide the basis for the
      current model of photoaging and the effects of tretinoin.

PMID- 11535422
TI  - Hormonal effects on skin aging.
AB  - With aging, there is a decrease in the level of hormones, such as estrogen,
      testosterone, dehydroepiandrosterone sulfate, and growth hormone. The effect of
      this decrease on the skin has been poorly documented, although more data are
      available for estrogen than for other hormones. This article reviews the effect
      of decreasing hormone levels on the skin and the possible cutaneous benefits of
      hormone replacement therapy.

PMID- 11535423
TI  - Quantitative assessment of skin aging.
AB  - Noninvasive methods have allowed physicians to give an objective description of
      aged skin in terms of functional and esthetic properties. The relative influence
      of environment (mainly sun) on the true aging process can be assessed through the
      obtained data. It is also possible to measure the efficacy of topical
      preparations (cosmetics or drugs) designed for treating the various cutaneous
      aging marks.

PMID- 11535424
TI  - Photodermatoses in the elderly.
AB  - Several photodermatoses specifically affect the elderly, and many others continue
      into old age. Photodermatoses present unique challenges in diagnosis and
      management when considered in the context of the multiple pathologies and
      problems of polypharmacy in this age group. This article examines the idiopathic
      photodermatoses, which include chronic actinic dermatitis, specifically a disease
      of the middle-aged and elderly. Endogenous (metabolic) and exogenous (drug and
      chemical) photodermatoses, as well as photo-exacerbated dermatoses, also are
      discussed.

PMID- 11535425
TI  - Skin cancer in the elderly.
AB  - This article describes the clinical features, treatment options, and prognosis of
      the most common skin cancers: basal cell carcinoma, squamous cell carcinoma, and
      melanoma. Emphasis is placed on specific issues that need to be considered when
      dealing with cancers of the skin in the elderly population. In addition, issues
      surrounding the early detection and prevention of skin cancer are addressed.

PMID- 11535426
TI  - Papulosquamous disorders of the elderly.
AB  - Several papulosquamous skin conditions occur in the elderly, including inherited
      and acquired ichthyoses, psoriasis, cutaneous lymphoma, and cutaneous connective
      tissue diseases. The clinical presentations can be quite helpful in diagnosing
      these conditions, and confirmatory histology and immunologic testing can often
      better define the specific entities. Treatment often involves identifying
      underlying systemic causes, as well as specific approaches based on the diagnosis
      and severity of clinical presentation.

PMID- 11535427
TI  - Lasers and cosmetic dermatologic surgery for aging skin.
AB  - Many topical agents and physical modalities have been used throughout the years
      to give the face a more youthful appearance. The goal has always been to
      effectively and consistently rejuvenate the face while minimizing the time of
      recovery and risk for complications. Because each person is unique, there is no
      one modality that is best for everyone. This article reviews some of the options
      available for treating photoaged skin in 2001. Various lasers (e.g., vascular
      lesion, pigmented lesion, hair removal, and resurfacing), botulinum A toxin,
      chemical peels, and various dermal and subcutaneous filler substances all are
      discussed.

PMID- 11535429
TI  - Vitrectomy and membrane dissection surgery.

PMID- 11535431
TI  - Periorbital and orbital cellulitis after H. influenza B vaccination.

PMID- 11535432
TI  - Egna-Neumarkt glaucoma study.

PMID- 11535434
TI  - Active ocular syphilis.

PMID- 11535435
TI  - ACE and angiotensin II and nonarteritic anterior ischemic optic neuropathy.

PMID- 11535436
TI  - Silicone oil tamponade to seal macular holes.

PMID- 11535438
TI  - Lymphoma mimicking scleritis.

PMID- 11535439
TI  - Induced myopia associated with capsular bag distension syndrome.

PMID- 11535440
TI  - Staphylococcus epidermidis and intraocular lenses.

PMID- 11535441
TI  - Corneal complications and NSAIDs.

PMID- 11535444
TI  - Radiation therapy for Graves' ophthalmopathy: trick or treat?

PMID- 11535445
TI  - A prospective, randomized, double-blind, placebo-controlled study of orbital
      radiotherapy for Graves' ophthalmopathy.
AB  - CONTEXT: Although widely used for more than 85 years, the efficacy of
      radiotherapy for Graves' ophthalmopathy (GO) has not been established
      convincingly. OBJECTIVE: To evaluate the efficacy of radiotherapy for GO. DESIGN:
      Prospective, randomized, internally controlled, double-blind clinical trial in a
      tertiary care academic medical center. PARTICIPANTS: The patients were ethnically
      diverse males and females over age 30 seen in a referral practice. The patients
      had moderate, symptomatic Graves' ophthalmopathy (mean clinical activity score,
      6.2) but no optic neuropathy, diabetes, recent steroid treatment, previous
      decompression, or muscle surgery. Forty-two of 53 consecutive patients were
      enrolled after giving informed consent and fulfilling study entry criteria.
      Eleven eligible patients declined to participate because of inconvenience, desire
      for alternative therapy, or concern about radiation. INTERVENTION: One randomly
      selected orbit was treated with 20 Gy of external beam therapy; sham therapy was
      given to the other side. Six months later, the therapies were reversed. MAIN
      OUTCOME MEASURES: Every 3 months for 1 year, we measured the volume of
      extraocular muscle and fat, proptosis, range of extraocular muscle motion, area
      of diplopia fields, and lid fissure width. Effective treatment for GO will modify
      one or more of these parameters. RESULTS: No clinically or statistically
      significant difference between the treated and untreated orbit was observed in
      any of the main outcome measures at 6 months. At 12 months, muscle volume and
      proptosis improved slightly more in the orbit that was treated first.
      CONCLUSIONS: In this group of patients, representative of those for whom
      radiotherapy is frequently recommended, we were unable to demonstrate any
      beneficial therapeutic effect. The slight improvement noted in both orbits at 12
      months may be the result of natural remission or of radiotherapy, but the changes
      are of marginal clinical significance.

PMID- 11535446
TI  - Australasian orbital and adnexal Wegener's granulomatosis.
AB  - OBJECTIVE: To report a retrospective case series of 29 Australian and New Zealand
      patients with orbital and adnexal Wegener's granulomatosis (WG). DESIGN:
      Retrospective case series. PARTICIPANTS: Twenty-nine cases of orbital and adnexal
      WG were identified. METHODS: A number of oculoplastic surgeons and other
      clinicians in Australia and New Zealand was asked about their experience with
      orbital and adnexal WG. Clinical data regarding these cases were conveyed by
      means of a questionnaire. Cases of ophthalmic WG without features of orbital or
      adnexal disease were excluded. MAIN OUTCOME MEASURES: Data obtained from the
      questionnaire includes age, gender, limited or generalized disease,
      antineutrophil cytoplasmic antibody (ANCA) status, symptoms and signs:
      nasolacrimal obstruction, sinusitis, fistula/orbital bone erosion, orbital
      mass/proptosis, extraocular muscle/diplopia, visual acuity reduction caused by
      optic nerve compression, orbital pain, lid edema/erythema, biopsy status, and
      treatment status. RESULTS: Twenty-nine patients with orbital and adnexal WG were
      identified and described. Symptoms included awareness of an orbital mass,
      epiphora, orbital pain and diplopia. Signs included an orbital mass or proptosis
      (69%), nasolacrimal duct obstruction (52%), limited ocular rotations (52%), lid
      erythema and edema (31%), bony destruction (21%), and reduced visual acuity
      (17%). Two patients had a persistent nasolacrimocanthal fistula. Cytoplasmic
      pattern antineutrophil cytoplasmic antibodies (c-ANCA) were present in 52% of
      patients, and in 9 of 10 patients with generalized disease. However, c-ANCA was
      positive in only 32% (6 of 19) of patients with limited WG. Perinuclear pattern
      antineutrophil cytoplasmic antibodies (p-ANCA) was positive in 10% of cases.
      CONCLUSIONS: To diagnose and treat ophthalmic WG effectively, the clinician must
      be aware of its protean orbital and adnexal manifestations. WG may occur with or
      without systemic involvement, and c-ANCA was negative in approximately half our
      cases. Our cases also demonstrated two orbital fistulae, an observation
      previously believed to be rare.

PMID- 11535447
TI  - Presbyopia, accommodation, and the mature catenary.
AB  - OBJECTIVE: To demonstrate a plausible explanation of aging changes and to reduce
      the controversy relative to accommodation by using a mechanical model of the
      catenary theory of lens change. MECHANICAL MODELING: A mechanical model was used
      to simulate a human lens in both the accommodated and unaccommodated state to
      demonstrate changes in the mechanism of accommodation with age. METHODS: Fluid
      filled latex balloons were supported by a plastic wrap hammock to form a catenary
      that models the human lens. Increasing volumes were used to simulate that of the
      aging lens, and variations in curvature were measured. MAIN OUTCOME MEASURES: The
      degree of curvature of a simulated anterior lens surface was measured and
      compared with mathematical modeling of its optical surface based on the catenary
      hydraulic suspension theory. RESULTS: The measurements showed that accommodative
      loss and other features such as mass displacement, reproducible lens surfaces,
      and zonule support are consistent with the catenary theory of accommodation and
      an increasing lens volume with age. CONCLUSIONS: The catenary theory of
      accommodation provides a basis for evaluating age changes of the human lens.
      Variable results with surgical procedures for presbyopia are also predictable
      with the model. These results can be used to provide a basis for intraocular lens
      design.

PMID- 11535448
TI  - Long-term follow-up of occlusion therapy in amblyopia.
AB  - OBJECTIVE: To determine whether the results of occlusion therapy for amblyopia
      are maintained into adulthood. DESIGN: Prospective, observational case series.
      PARTICIPANTS: Fifty-four patients, who were successfully treated in childhood for
      unilateral amblyopia by occlusion, were followed up to the age of 9 years, were
      evaluated in 1984 for long-term results 6.4 years on average after cessation of
      treatment, and accepted our invitation for reevaluation in 1999. METHODS: All
      patients were given a complete eye examination. The visual acuity (VA) was
      measured. RESULTS: The average period of follow-up was 21.5 years (range, 17.2
      25.1 years). The mean age at the most recent examination was 29.0 +/- 2.1 years
      (range, 25.1-34). At this examination, a best-corrected visual acuity (BCVA) of
      20/40 or better was achieved by 72.3% of the patients. The mean BCVA was 20/35
      (20/25-20/70) at the end of occlusion therapy, 20/45 (20/20-20/300) in 1984, and
      20/34 (20/15-20/100) at the present examination. Relative to the results at the
      end of therapy, BCVA at the present examination was maintained or improved in
      66.7% of the patients. Relative to 1984, the BCVA in 1999 was maintained or
      improved in 87% of the patients. MAIN OUTCOME MEASURE: Visual acuity. CONCLUSION:
      Comparative evaluation of BCVA at a long-term follow-up examination, performed
      21.5 years on average after cessation of occlusion therapy, showed that VA was
      maintained or improved in two thirds of patients who had been successfully
      treated by occlusion for unilateral amblyopia in childhood.

PMID- 11535449
TI  - Excessive blinking in childhood: a prospective evaluation of 99 children.
AB  - OBJECTIVE: To determine the characteristics and causes of excess blinking in
      children and to determine outcomes after treatment. DESIGN: Prospective,
      noncomparative, consecutive case series. PARTICIPANTS: Ninety-nine consecutive
      children who presented for evaluation of excessive blinking over a 2 year period.
      METHODS: Children less than 16 years of age who had excessive blinking as their
      sole or major chief complaint underwent detailed history and ophthalmologic
      examination. Treatment was recommended based on clinical examination findings.
      Follow-up evaluations were performed at least 2 months after initial examination.
      MAIN OUTCOME MEASURES: Etiology of excess blinking and patient characteristics in
      each diagnostic group. RESULTS: The majority (89%) of children presented with
      bilateral excessive blinking. Boys outnumbered girls at a ratio of almost 2:1.
      The most common etiologies were anterior segment and/or lid abnormalities (37%),
      habit tics (23%), uncorrected refractive errors (14%), intermittent exotropia
      (11%), and psycogenic blepharospasm (10%). A history of neurologic disease was
      present in 22% of the patients but was not causally related to the excessive
      blinking in most cases. Vision-threatening disease was noted in 6% and was easily
      detected on standard clinical examination. Life-threatening disease was the cause
      in 4% of the children, but the presence of life-threatening disease was already
      known in all such patients. CONCLUSIONS: Excessive blinking in children can occur
      because of a large number of potential problems. Most cases are caused by benign
      and/or self-limiting conditions. The cause can usually be determined after
      careful history and clinical examination and routine neurologic evaluation and
      neuroimaging is unnecessary.

PMID- 11535450
TI  - Pediatric dacryocystorhinostomy for nasolacrimal duct obstruction.
AB  - OBJECTIVE: To determine the outcome of pediatric dacryocystorhinostomy (DCR) for
      large mucoceles or for primary nasolacrimal duct obstruction unresponsive to
      multiple probings. DESIGN: Retrospective noncomparative case series.
      PARTICIPANTS: One hundred thirty-four external dacryocystorhinostomies were
      performed in 121 children. METHODS: Clinical case notes were reviewed for a
      series of cases operated on at Moorfields Eye Hospital by specialist lacrimal
      surgeons between 1987 and 1999. MAIN OUTCOME MEASURES: Postoperative relief of
      presenting symptoms and signs and complications. RESULTS: Fifty-nine percent of
      admissions (75 of 127) were day cases, and the other 52 admissions were
      inpatient. Simultaneous bilateral surgery was performed in 7 of 121 (6%)
      children, all but one having day case admission, and sequential bilateral surgery
      in 6 of 121 (5%) cases. Silicone intubation was performed in 20% of operations,
      these generally being early in the series. Three children had Down syndrome, five
      had craniofacial anomalies, and two had systemic disorders. Mild postoperative
      cellulitis occurred in three cases, all of which settled without complication
      after systemic antibiotic therapy, and there was one case of suture granuloma.
      There were no cases of immediate postoperative complication in either the day
      case or the inpatient groups. Complete cure of symptoms was achieved in 96% and
      an improvement of symptoms (with mild persistence of epiphora under challenge) in
      five cases (4%). CONCLUSION: For surgeons experienced in pediatric lacrimal
      surgery, external DCR with sutured mucosal flaps can be accomplished through an 8
      mm incision with no surface sutures and minimal scarring. Symptoms are improved
      in all cases and complete cure achieved in 96%, with no immediate postoperative
      complications and only few (3%) short-term complications. The surgery is amenable
      to day case management, without significant morbidity, and may be performed as a
      simultaneous bilateral procedure.

PMID- 11535451
TI  - Treatment of ocular cicatricial pemphigoid with sulfasalazine.
AB  - PURPOSE: To assess the outcome of patients with ocular cicatricial pemphigoid
      (OCP) treated with sulfasalazine as an alternative to dapsone. DESIGN:
      Retrospective noncomparative case series. PARTICIPANTS: Nine patients with biopsy
      proven OCP and previous dapsone-related adverse effects (hemolysis and
      gastrointestinal disturbances) treated with oral sulfasalazine. METHODS: Clinical
      data were abstracted from patients' medical records. MAIN OUTCOME MEASURES:
      Patients' symptoms, ocular inflammation, conjunctival scarring, complete blood
      cell count (including reticulocyte count). RESULTS: At the initiation of
      sulfasalazine therapy, ocular inflammation was controlled in all patients but
      one. Mean follow-up was 12 months (range, 2-35 months). Median oral sulfasalazine
      dosage was 3 g (range, 1-4 g). The disease remained controlled with sulfasalazine
      alone in four patients (45%). Two patients (22%) required adjunctive oral
      cyclophosphamide. Adverse effects necessitating drug withdrawal occurred in three
      patients (33%): hemolysis in two and gastrointestinal disturbances in one.
      CONCLUSIONS: Sulfasalazine may be useful in OCP patients with previous dapsone
      related adverse effects.

PMID- 11535452
TI  - Cultivated corneal epithelial stem cell transplantation in ocular surface
      disorders.
AB  - PURPOSE: To investigate the outcome of cultivated corneal epithelial
      transplantation for severe stem cell deficiencies using denuded amniotic membrane
      (AM) as a carrier. DESIGN: Retrospective, noncomparative case series.
      PARTICIPANTS: Thirteen eyes of 11 patients were studied. These consisted of five
      eyes with acute Stevens-Johnson syndrome (SJS), two with chronic SJS, one with an
      acute chemical injury, two with chronic chemical injuries, two with ocular
      cicatricial pemphigoid, and one with drug-induced pseudopemphigoid. All of these
      eyes had total stem cell deficiencies. MAIN OUTCOME MEASURES: Adaptation of the
      cultivated corneal epithelium onto the host corneal surface was confirmed 48
      hours after surgery. The reconstruction of the ocular surface and visual acuity
      were measured. METHODS: Corneal limbal epithelium from donor corneas was
      cultivated for 4 weeks on a denuded AM carrier, with 3T3 fibroblast coculture and
      air lifting. The cultivated corneal epithelium showed four to five layers of
      stratification and was well differentiated. After conjunctival tissue removal
      from the cornea up to 3 mm outside the limbus and subconjunctival tissue
      treatment with 0.04% mitomycin C, cultivated allocorneal epithelium, including
      the AM carrier, was transplanted onto the corneal surface up to the limbus.
      Lamellar keratoplasty, using preserved donor graft without epithelium, was
      performed simultaneously for five chronic-phase patients showing corneal stromal
      scarring. Systemic immunosuppression was used to prevent allograft rejection.
      RESULTS: In all 13 eyes, the entire corneal surface, on which cultivated
      allocorneal epithelium had been placed, was free from epithelial defects 48 hours
      after surgery, indicating complete survival of the transplanted corneal
      epithelium. Visual acuity improved in all eyes after surgery, and 10 of the 13
      eyes were restored to good vision (postoperative visual acuity improved two or
      more lines) 6 months after the operation. During the follow-up period (mean +/-
      standard deviation, 11.2 +/- 1.3 months), the corneal surfaces were clear,
      although three eyes experienced epithelial rejection. CONCLUSIONS: Cultivated
      corneal epithelial transplantation using denuded AM as a carrier can be used for
      severe stem cell deficiencies.

PMID- 11535453
TI  - Management and prognosis of Merkel cell carcinoma of the eyelid.
AB  - OBJECTIVE: To evaluate the clinical presentation, treatment, and long-term follow
      up of eyelid Merkel cell carcinoma. DESIGN: Retrospective noncomparative
      interventional case series. PARTICIPANTS: Fourteen patients with primary eyelid
      Merkel cell carcinoma. METHODS: Cases of Merkel cell carcinoma for which long
      term follow-up was available were solicited from members of the American Society
      of Ophthalmic Plastic and Reconstructive Surgery through an on-line e-mail/news
      group. MAIN OUTCOME MEASURES: Follow-up period, treatment history, presence and
      type of recurrence, and mortality. RESULTS: Average follow-up was 33.4 months. Of
      the 14 cases identified, only 2 patients (14%) received prophylactic therapy
      beyond wide surgical excision. Three patients (21%) had recurrences, none of whom
      initially received prophylactic therapy (i.e., radiation therapy, lymph node
      dissection, and/or chemotherapy) beyond wide surgical excision. One patient (7%)
      died of metastatic Merkel cell carcinoma. CONCLUSIONS: Merkel cell carcinoma is a
      rare skin malignancy that occasionally affects the eyelid, with the potential for
      regional and distant metastasis. Consideration should be given to the use of
      prophylactic adjunctive therapies beyond wide surgical excision while
      simultaneously considering the morbidity of these therapies.

PMID- 11535454
TI  - Ocular manifestations of tuberculosis.
AB  - OBJECTIVE: To present the clinical and histopathologic findings in five cases of
      tuberculosis (TB) with various ocular manifestations. DESIGN: Observational case
      series. METHODS: Retrospective review of clinical findings, course, and treatment
      of five patients. Diagnostic techniques, including biomicroscopic,
      histopathologic, and molecular biologic test results, are presented. MAIN OUTCOME
      MEASURES: Visual acuity, slit-lamp biomicroscopy, indirect ophthalmoscopy, and
      fluorescein angiography results. RESULTS: The ocular manifestations of TB in our
      patients included panophthalmitis, endophthalmitis, posterior uveitis with
      choroidal tubercles, keratitis, and a lid mass. Mycobacterium tuberculosis was
      identified in four cases in ocular specimens using acid-fast bacilli microscopy
      and in three cases by culture. Rapid diagnosis using polymerase chain reaction
      was obtained in one case. Extraocular foci of TB were identified in three cases
      with an intraocular infection at presentation. No patients had the human
      immunodeficiency virus (HIV) and none were immunocompromised. Two eyes could not
      be saved using antituberculous treatment because of delayed diagnosis and
      treatment. CONCLUSIONS: In this age of the HIV pandemic, TB is becoming more
      common. Because it is curable, heightened awareness and better understanding of
      the disease's ocular manifestations should be of concern to all ophthalmologists.

PMID- 11535455
TI  - Optic disc morphology after arteritic anterior ischemic optic neuropathy.
AB  - OBJECTIVE: To evaluate the appearance of the nerve head in patients after giant
      cell arteritis-induced arteritic anterior ischemic optic neuropathy (A-AION).
      DESIGN: Noncomparative clinical case series. PATIENTS: The study comprised 29
      patients who presented with unilateral A-AION and temporal artery biopsy-proven
      giant cell arteritis. Stereoscopic optic disc photographs, taken of both the
      affected and unaffected eyes at the onset of the disease and after a follow-up
      period of 20.10 +/- 25.36 months (median, 11 months; range, 2-102 months), were
      morphometrically evaluated. MAIN OUTCOME MEASURES: Size and shape of the optic
      disc, neuroretinal rim, optic cup, and alpha and beta zones of parapapillary
      atrophy. RESULTS: In the eyes after A-AION, at the end of the study, the
      neuroretinal rim was significantly (P = 0.002) smaller, and the optic disc cup
      area was significantly (P = 0.001) larger than those of the contralateral
      unaffected eyes. Alpha zone and beta zone of parapapillary atrophy did not vary
      significantly (P > 0.50). CONCLUSIONS: A-AION, like glaucomatous optic
      neuropathy, results in neuroretinal rim loss and optic disc cupping. However, in
      contrast to glaucoma, A-AION is not associated with an enlargement of
      parapapillary atrophy. The reasons and mechanisms responsible for these
      similarities and dissimilarities are discussed. Marked clinical, morphologic, and
      histopathologic similarities in optic disc cupping and loss of neuroretinal rim
      between A-AION and glaucomatous optic neuropathy are highly suggestive of a
      common mechanism for the development of the two diseases (i.e., ischemia of the
      optic nerve head). The subject is discussed at length.

PMID- 11535456
TI  - Disc excavation in dominant optic atrophy: differentiation from normal tension
      glaucoma.
AB  - OBJECTIVE: In patients with dominant optic atrophy (DOA, Kjer type), excavation
      of the optic nerve develops, and these patients may be misdiagnosed as having
      normal tension glaucoma (NTG). This study examined disc morphologic features in
      patients with DOA and explored features that help distinguish this condition from
      NTG. DESIGN: Noncomparative, observational case series. PARTICIPANTS: Patients
      with DOA who were seen at the Duke University Eye Center between 1987 and 1996
      and who had bilateral optic nerve photographs. METHODS: Retrospective chart
      review of the results of visual acuity testing, visual field testing by Goldmann
      perimetry, color vision testing, intraocular pressure measurement, and
      observation of bilateral optic nerve photographs. MAIN OUTCOME MEASURES:
      Appearance of the optic disc and peripapillary zone in patients with DOA.
      RESULTS: Nine patients were identified. The mean age at the time of evaluation
      was 28 years (range, 11-62 years). Most patients had a mild to moderate reduction
      in visual acuity. Color vision as tested with Hardy-Rand-Rittler plates was
      reduced (4.0/10 +/- 4.2/10). A cup-to-disc ratio of more than 0.5 was observed in
      at least one eye of eight patients. A temporal wedge-shaped area of excavation
      was observed in 14 of the 18 eyes studied. Moderate to severe temporal pallor was
      observed in all of the eyes. Pallor of the remaining (noncupped) neuroretinal rim
      was also observed consistently, ranging from mild to moderate. A gray crescent
      and some degree of peripapillary atrophy were noted in all eyes. CONCLUSIONS:
      Several clinical features, including early age of onset, preferential loss of
      central vision, sparing of the peripheral fields, pallor of the remaining
      neuroretinal rim, and a family history of unexplained visual loss or optic
      atrophy, help to distinguish patients with DOA from those with NTG.

PMID- 11535457
TI  - Angle-closure glaucoma in association with orbital pseudotumor.
AB  - PURPOSE: To describe the pathophysiology of angle-closure glaucoma secondary to
      idiopathic inflammatory orbital pseudotumor. DESIGN: Retrospective, small
      noncomparative case series. PARTICIPANTS: Three patients with angle-closure
      glaucoma and orbital pseudotumor. METHODS: The pathophysiology of this entity was
      investigated using magnetic resonant imaging (MRI) and ultrasound biomicroscopy
      (UBM). MAIN OUTCOMES MEASURES: Clinical features, anterior chamber angle
      configuration, and intraocular pressure. RESULTS: Angle closure from anterior
      rotation of the ciliary body caused by choroidal effusions secondary to
      pseudotumor was demonstrated using MRI and UBM. Two of the three cases resolved
      after treatment for orbital pseudotumor. CONCLUSIONS: Idiopathic orbital
      pseudotumor is a cause of secondary angle-closure glaucoma. The mechanism of
      angle closure is anterior rotation of the ciliary body secondary to choroidal
      effusions resulting from the orbital inflammation.

PMID- 11535458
TI  - Evidence for genetic heterogeneity within eight glaucoma families, with the GLC1A
      Gln368STOP mutation being an important phenotypic modifier.
AB  - OBJECTIVE: To investigate the phenotype and age-related penetrance of primary
      open-angle glaucoma (POAG) in Australian families with the most common Myocilin
      mutation (Gln368STOP). DESIGN: Cross-sectional genetic study. PARTICIPANTS: Eight
      pedigrees carrying the Gln368STOP mutation were ascertained from 1730 consecutive
      cases of POAG in the Glaucoma Inheritance Study in Tasmania. METHODS: Index cases
      and available family members were examined for signs of glaucoma, and the
      presence of the GLC1A Gln368STOP mutation was ascertained by single-strand
      conformation polymorphism analysis and subsequent direct sequencing. RESULTS:
      From the eight pedigrees, 29 Gln368STOP mutation-carrying individuals with either
      ocular hypertension (OHT) or POAG were found, with a mean age at diagnosis of
      52.4 +/- 12.9 years and a mean peak intraocular pressure (IOP) of 28.4 +/- 4.7
      mmHg. A further 11 mutation carriers older than 40 years have been studied, who
      as yet show no signs of OHT or POAG. Within the 8 pedigrees, a further 31
      individuals with OHT or POAG were identified who did not carry the Gln368STOP
      mutation. For these individuals the mean age at diagnosis was higher (62.3 +/-
      13.7 years, P < 0.01), and the mean peak IOP was lower (25.4 +/- 6.4 mmHg, P =
      0.01). For Gln368STOP carriers, age-related penetrance for OHT or POAG was 72% at
      age 40 years and 82% at age 65 years. A positive family history of POAG was
      present in all index cases. Five of the eight pedigrees had a positive family
      history on both maternal and paternal sides. Seven of the eight pedigrees had one
      or more individuals with POAG who did not carry the mutation. Eight of the 29
      Gln368STOP carriers with OHT or POAG had undergone trabeculectomy. CONCLUSIONS:
      The GLC1A Gln368STOP mutation is associated with POAG, which in the pedigrees
      studied is of a younger age of onset and higher peak IOP than non-mutation
      glaucoma cases. In addition, Gln368STOP mutation glaucoma cases were more likely
      to have undergone glaucoma drainage surgery. We have not observed simple
      autosomal dominant inheritance patterns for POAG in these pedigrees. Other
      factors, as yet uncharacterized, are involved in expression of the POAG phenotype
      in Gln368STOP pedigrees.

PMID- 11535460
TI  - Clinical ability of Heidelberg retinal tomograph examination to detect
      glaucomatous visual field changes.
AB  - PURPOSE: To determine the agreement between Heidelberg Retinal Tomograph (HRT;
      Heidelberg Instruments, Heidelberg, Germany) and visual field examinations in
      differentiating normal from glaucomatous eyes and to evaluate the sensitivity and
      specificity of HRT optic disc examination in detecting eyes with glaucomatous
      damage. STUDY DESIGN: Cross-sectional study. PARTICIPANTS: Three hundred fifty
      nine patients, for a total of 359 eyes (55 normal, 209 with ocular hypertension
      [OHT], and 95 with primary open-angle glaucoma). INTERVENTION: Optic disc imaging
      by HRT, using a 10 degrees angle view; a mean of three repeated images were
      analyzed using version 2.01 software. The optic disc was classified as
      "normal/glaucomatous" on the basis of multivariate discriminant analysis and
      cumulative frequency distribution (ranked-segment distribution curves). The
      visual field was examined using the DS 30 II program (Humphrey perimeter, Zeiss
      Humphrey System, Dublin, CA), with a glaucomatous visual field being defined on
      the basis of an abnormal glaucoma hemifield test and a statistically significant
      corrected pattern standard deviation less than 4 dB. MAIN OUTCOME MEASURES:
      Agreement between HRT and visual field examinations calculated by means of the
      kappa statistic and the sensitivity and specificity of HRT examination. RESULTS:
      The agreement between the visual field-based and HRT definition of glaucoma was
      fair to poor, with a kappa statistic of between 0.48 and 0.28. The sensitivity
      and specificity of the HRT examination were, respectively, 80% and 65%, according
      to Mikelberg's analysis, and, respectively, 31% to 53% and 90% to 92%, according
      to the analysis based on cumulative curves of normality. CONCLUSIONS: In a broad
      clinical setting including normal, OHT, and glaucoma patients, the HRT and visual
      field tests have fair to poor agreement in detecting glaucoma. The HRT
      demonstrated a lack of specificity when using Mikelberg's multivariate
      discriminant analysis and a lack of sensitivity when using cumulative frequency
      distribution (ranked-segment distribution) curves. These values did not change
      when normal or OHT patients were excluded from the analysis. In the clinical
      setting, caution should be used when interpreting HRT results on the basis of
      multivariate discriminant analysis or cumulative frequency distribution curves.

PMID- 11535461
TI  - Surgical management of secondary glaucoma after pars plana vitrectomy and
      silicone oil injection for complex retinal detachment.
AB  - OBJECTIVE: To evaluate the outcomes of surgical intervention for secondary
      glaucoma after pars plana vitrectomy and silicone oil injection for repair of
      complex retinal detachment. DESIGN: Retrospective noncomparative interventional
      case series. PARTICIPANTS: Forty-three eyes of 43 patients who underwent
      incisional surgery for secondary glaucoma after pars plana vitrectomy and
      silicone oil injection for repair of complex retinal detachment over a 9-year
      period. MAIN OUTCOME MEASURES: Intraocular pressure (IOP), intraoperative and
      postoperative complications, visual acuity, and the need for further surgical
      intervention for glaucoma. Success was defined as IOP < or =21 mmHg and > or =5
      mmHg with or without medication but without surgical reoperation for glaucoma.
      RESULTS: Findings associated with elevated IOP included emulsified oil in the
      anterior chamber (n = 14), pupillary block from silicone oil (n = 13), open-angle
      glaucoma without silicone oil in the anterior chamber (n = 9), and angle-closure
      glaucoma without pupillary block (n = 7). The mean (+/- standard deviation) IOP
      was 41.4 +/- 15.1 mmHg before surgery for glaucoma and 17.2 +/- 10.2 mmHg after
      an average follow-up of 19.6 months (P < 0.001). Cumulative success was 69%, 60%,
      56%, and 48% at 6, 12, 24, and 36-months respectively. In patients who underwent
      silicone oil removal alone for surgical management of glaucoma (n = 32), 11 of 12
      IOP failures (92%) were due to uncontrolled IOP, whereas most IOP failures in the
      group who underwent silicone oil removal plus glaucoma surgery (n = 8) failed
      because of hypotony (3 of 4, 75%, P = 0.027). Of three patients who underwent
      glaucoma surgery alone to control IOP, one failed because of hypotony. There was
      no significant change in visual function at last follow-up (logarithm of the
      minimum angle of resolution [logMAR] 2.01) compared with preoperative visual
      function (logMAR 2.07, P = 0.74). CONCLUSION: Surgical management of secondary
      glaucoma after silicone oil injection for complex retinal detachment may achieve
      good IOP control and stabilization of visual function in most patients. Patients
      who undergo silicone oil removal alone to control IOP are more likely to have
      persistent elevation of IOP and possibly undergo reoperation for glaucoma,
      whereas patients who undergo concurrent silicone oil removal and glaucoma surgery
      are more likely to have hypotony.

PMID- 11535462
TI  - Vitrectomy for retained lens material after cataract extraction: the relationship
      between histopathologic findings and the time of vitreous surgery.
AB  - PURPOSE: To report the histopathologic features of vitreous specimens obtained
      after vitrectomy for retained lens material and to correlate these findings with
      the time after cataract surgery at which vitreous surgery was performed. DESIGN:
      Observational case series. PARTICIPANTS: All 135 patients who had vitreous
      specimens submitted to the pathology laboratory after vitreous surgery for
      retained lens material after elective senile cataract surgery. METHODS: A review
      of histopathologic reports of 135 consecutive vitreous specimens that were
      obtained during vitreous surgery for retained lens material after surgery for
      senile cataract. MAIN OUTCOME MEASURES: Identification of lens material,
      macrophages, phacolytic cells, and giant cells in the vitrectomy specimens.
      RESULTS: Lens material was observed in 100% of cases. Macrophages without
      ingested lens material were present in 48% (65 of 135), phacolytic cells in 24%
      (32 of 135), and a mixture of neutrophils and multinucleated giant cells in 8%
      (11 of 135). No cells were discovered in eyes in which vitrectomy was performed
      within 3 days of cataract extraction. The percentages of eyes with macrophages
      increased from 35% when vitrectomy was performed 4 to 7 days after cataract
      surgery to 80% when this time interval was 61 to 90 days. CONCLUSION: Lens
      induced inflammatory reaction seems to increase with time that retained lens
      material remains in the eye.

PMID- 11535463
TI  - Fundus changes corresponding to visual field defects after vitrectomy for macular
      hole.
AB  - OBJECTIVE: Visual field defects are one of the complications of macular hole
      surgery, and mechanical retinal damage induced by infusion air is a proposed
      causative factor of this complication. In this study, we examined the fundus to
      see whether the changes observed corresponded to postoperative visual field
      defects. DESIGN: Observational case series. PARTICIPANTS: Seventeen eyes of 17
      patients who had postoperative visual field defects after vitrectomy for
      idiopathic macular hole were examined. METHODS: The fundus was examined by
      ophthalmoscopy and by fluorescein and indocyanine green angiography. MAIN OUTCOME
      MEASURES: Fundus changes corresponding to postoperative visual field defects.
      RESULTS: In eight eyes, detectable fundus changes were observed, including
      regional mottling and degeneration of the retinal pigment epithelium, filling
      delay of the choroidal circulation, subretinal fibrosis, and epiretinal membrane
      formation. These findings corresponded exactly to the visual field defects
      observed. Although the visual field defects had been detected shortly after
      surgery, fundus changes were detected, on average, more than 8 months after
      surgery. CONCLUSIONS: Fundus changes become apparent after surgery, and they are
      progressive. Therefore, it is important to examine eyes with visual field defects
      for a follow-up period of several years.

PMID- 11535464
TI  - Outcomes after laser therapy for threshold retinopathy of prematurity.
AB  - OBJECTIVE: To determine the anatomic outcomes of eyes treated with laser
      photocoagulation for threshold retinopathy of prematurity and to identify
      potential risk factors for unfavorable outcomes after treatment. DESIGN:
      Retrospective, noncomparative case series. INTERVENTION: Photocoagulation of the
      peripheral avascular retina with an argon or diode laser indirect ophthalmoscope.
      PARTICIPANTS: One hundred twenty eyes of 81 infants with threshold retinopathy of
      prematurity treated with laser photocoagulation from 1989 through 1997 with at
      least 12 months of follow-up after treatment. MAIN OUTCOME MEASURES: The
      principal outcome was the presence of an unfavorable anatomic outcome defined as
      a retinal detachment, macular fold, or retrolental tissue. RESULTS: One hundred
      nine of 120 eyes (91%) had favorable outcomes. Eleven eyes (9%) had retinal
      detachments, and 1 of the 11 also had retrolental tissue. Zone 1 eyes appeared to
      be 3.3 times more likely to have an unfavorable outcome compared with zone 2
      eyes, but the 95% confidence interval (0.8-14.5) did not support this
      statistically. Twenty-four of 109 eyes (22%) experienced dragging of the temporal
      vessels. Those with zone 1 disease were 13.7 times more likely to experience
      temporal dragging compared with zone 2 eyes (95% confidence interval, 3.3-57.2).
      CONCLUSIONS: After laser photocoagulation for threshold retinopathy of
      prematurity, 91% of eyes had a favorable anatomic outcome. Compared with zone 2
      eyes, zone 1 eyes may be more likely to have temporal dragging of the retinal
      vessels. Laser therapy is effective in the treatment of threshold retinopathy of
      prematurity.

PMID- 11535465
TI  - Adult retinopathy of prematurity: outcomes of rhegmatogenous retinal detachments
      and retinal tears.
AB  - PURPOSE: To describe the results of retinal tears and rhegmatogenous retinal
      detachments (RD) in adults with retinopathy of prematurity (ROP). DESIGN:
      Noncomparitive interventional case series. METHODS: Retrospective cohort of 216
      eyes of 108 patients, 15 years or older, followed for up to 23 years (median, 6.2
      years). RESULTS: One eye was initially seen with an RD, and during follow-up 30
      eyes had an RD develop. An additional surgical procedure was required in 7 of the
      31 eyes (23%) with an RD. Four eyes were initially seen with retinal tears, and
      during follow-up 19 eyes had a retinal tear develop. Seven of the 23 eyes (30%)
      with a retinal tear had initial repair fail. Eyes with minimal cicatricial
      changes from ROP were still at high risk for tears and detachments developing.
      Eighty percent of eyes with retinal tears and 60% of eyes with an RD that started
      with vision >20/60 maintained that level of vision at the final examination.
      CONCLUSION: In patients with a history of premature birth, features of fundus
      examinations do not correlate with the occurrence of a retinal tear or RD. Repair
      of a tear or detachment in such a patient is more likely to require multiple
      procedures but can still be associated with good visual results. Physicians
      should consider widespread relief of vitreoretinal traction for a tear or
      detachment in any patient with a history of premature birth.

PMID- 11535467
TI  - Terson syndrome: a case report suggesting the mechanism of vitreous hemorrhage.
AB  - OBJECTIVE: To present a patient with Terson syndrome and to propose a mechanism
      for vitreous hemorrhage. DESIGN: Observational case report. PARTICIPANT: A 50
      year-old woman with subarachnoid hemorrhage and unilateral vitreous hemorrhage.
      METHODS: Detailed examination with fluorescein angiography and funduscopy. MAIN
      OUTCOME MEASURES: Site of dye leakage on fluorescein angiography in the eye with
      vitreous hemorrhage. RESULTS: Fluorescein angiography showed the leakage site at
      the margin of the disc in the eye with vitreous hemorrhage after the vitreous
      hemorrhage had been removed. CONCLUSIONS: The damage to peripapillary tissues
      demonstrated by fluorescein leakage suggests that intracranial hypertension
      affects peripapillary structures through the intervaginal space of the optic
      nerve sheath.

PMID- 11535468
TI  - Juxtapapillary subretinal pigment epithelial polypoid pseudocysts associated with
      unilateral tilted optic disc: case report with clinicopathologic correlation.
AB  - OBJECTIVE: To describe the unique preoperative appearance, successful
      postoperative clinical course, and histopathologic features of a cluster of
      progressively enlarging pseudocysts that arose at the temporal margin of a
      unilateral tilted optic disc. STUDY DESIGN: Case report. METHODS: Clinical
      observation, color fundus photography, fluorescein angiography, and optical
      coherence tomography, as well as routine histologic and immunohistochemical
      studies of tissue removed by subretinal surgery. RESULTS: Subretinal surgical
      excision of the lesions resulted in retinal reattachment with improved
      postoperative visual acuity. Histologic examination disclosed a cluster of fluid
      filled polypoid pseudocysts lined by small vessels of choroidal origin lying
      beneath the basement membrane of the overlying retinal pigment epithelium (RPE).
      CONCLUSIONS: We postulate that buds of small vessels of choroidal origin grew
      through or around the edge of Bruch's membrane at the temporal margin of the
      tilted optic disc and then passed under the juxtapapillary RPE. Ensuing leakage
      of proteinaceous fluid from these vessels eventuated in formation of a cluster of
      polypoid pseudocysts and subsequent localized papillomacular retinal separation
      with visual loss. The lesions were amenable to subretinal surgical removal with
      restoration of visual acuity.

PMID- 11535469
TI  - Relationships between vitreoretinal and refractive surgery.
AB  - OBJECTIVE: To describe retinal complications after posterior chamber phakic
      intraocular lens (PCPIOL) implantation and refractive surgery complications after
      scleral buckling surgery. DESIGN: Retrospective, noncomparative, small case
      series. PARTICIPANTS: Four patients in whom retinal detachment developed after
      PCPIOL implantation and two patients with previously placed encircling scleral
      buckles in whom corneal steepening developed after laser in situ keratomileusis
      (LASIK). INTERVENTION: The four patients with retinal detachment after PCPIOL
      implantation underwent vitreoretinal surgery. One of the two patients in whom
      corneal steepening developed after LASIK underwent buckle removal. MAIN OUTCOME
      MEASURES: The main parameters evaluated were vitreoretinal findings, corneal
      topography, and pachymetry. RESULTS: Retinal attachment was achieved for all
      patients. Mean postoperative best-corrected visual acuity (BCVA) was 20/30. One
      patient lost one line of BCVA. One patient with corneal steepening achieved
      partial corneal flattening after buckle removal. CONCLUSIONS: Vitreous base
      stimulation related to PCPIOL implantation and manipulation during LASIK may
      trigger retinal complications. Laser in situ keratomileusis in patients with
      previously placed scleral buckles may result in unexpected corneal steepening.

PMID- 11535472
TI  - Anterior capsule opacification: correlation of pathologic findings with clinical
      sequelae.
AB  - OBJECTIVE: To evaluate the degree of anterior capsule opacification (ACO) in
      human eyes obtained postmortem containing various rigid and foldable posterior
      chamber intraocular lens (PC-IOL) designs and compare the findings with clinical
      sequelae of capsular shrinkage. DESIGN: Comparative autopsy tissue study with
      clinicopathologic correlations. MATERIALS: Three hundred formalin-fixed human
      eyes containing the following PC-IOL styles were analyzed: (1) one-piece
      polymethyl methacrylate (PMMA) optic-PMMA haptic (n = 50), one-piece silicone
      plate IOL, with large (2) or small (3) fixation holes (n = 35), (4) three-piece
      PMMA optic-Prolene haptic (n = 50), (5) three-piece acrylic optic-PMMA haptic (n
      = 55), three-piece silicone optic with PMMA (6) or polyimide (7) haptics (n =
      30), and (8) three-piece silicone optic-Prolene haptic (n = 80) lenses. TESTING:
      The eyes were sectioned in the equatorial plane for gross examination of the
      capsular bag from a posterior view. The cornea and iris were then excised for
      evaluation from an anterior view. MAIN OUTCOME MEASURES: ACO was scored in each
      eye from 0 to IV, according to the degree/area of capsule opacification.
      Capsulorrhexis size and IOL decentration were measured with calipers. RESULTS:
      The overall differences among the IOL groups regarding the three parameters were
      significant (ACO score: P < 0.001; capsulorrhexis diameter: P = 0.036; IOL
      decentration: P = 0.012). Mean ACO scores were highest with the large- and small
      hole one-piece silicone-plate lenses (2.543 +/- 0.950) and lowest with the three
      piece acrylic optic-PMMA haptic lenses (0.600 +/- 0.710). Of 10 cases of
      capsulorrhexis phimosis observed in the study, 7 cases were associated with three
      piece silicone optic-Prolene haptic lenses, which also presented the highest mean
      decentration (0.375 +/- 0.601 mm). CONCLUSIONS: Our results confirm previous
      histopathologic observations that the rate of ACO is the lowest with acrylic
      lenses and higher with plate-haptic silicone IOLs. Nevertheless, clinical
      sequelae of capsular shrinkage are also very important with three-piece silicone
      optic-Prolene haptic designs. Thus, IOL material and design are significant
      factors in the development of ACO, but they ultimately also influence the
      clinical presentation of capsular shrinkage.

PMID- 11535471
TI  - Drug use and five-year incidence of age-related cataracts: The Beaver Dam Eye
      Study.
AB  - OBJECTIVE: To evaluate incident cataract after a 5-year interval with respect to
      medication use. DESIGN: Population-based incidence study. MAIN OUTCOME: Incident
      cataract judged from standard photographs. SETTING: Study subjects were adults 43
      to 86 years of age in 1988 to 1990 and again in 1993 to 1995. All participants
      were examined and interviewed, and photographs were taken. All procedures and
      grading were done by protocols at both examinations. All medications in current
      use, prescribed as well as over-the-counter, were brought to the examination
      site, and the names were recorded at that time. RESULTS: There were 678 drug
      preparations (active ingredients) being used at the baseline examination.
      Significantly lower incidences of nuclear cataracts 5 years later occurred in
      those who took thiazide diuretics (odds ratio [OR] = 0.79, 95% confidence
      interval [CI] 0.63, 1.00) and aspirin (OR = 0.76, 95% CI 0.61, 0.95) at the
      baseline examination. There were significantly more incident cortical cataracts
      in those taking oral steroids (OR = 2.59, 95% CI 1.45, 4.62), amitriptyline (OR =
      2.03, 95% CI 1.09, 3.79), oral hypoglycemic agents (OR 2.06, 95% CI 1.23, 3.44),
      and insulin (OR = 3.38, 95% CI 1.61, 7.08). There were significantly more
      incident posterior subcapsular cataracts in those taking potassium-sparing
      diuretics (OR = 2.13, 95% CI 1.42, 3.18) and oral hypoglycemic agents (OR = 2.89,
      95% CI 1.57, 5.33). Considering past use with never and current use did not alter
      the patterns of associations. We were not able to separate the effects of
      antihypertensive or diuretic agents from that of hypertension. However,
      hypoglycemic agents were no longer associated with any cataract type after
      stratifying by diabetes status. CONCLUSIONS: Although many different medications
      were being used at the baseline examination in the Beaver Dam Eye Study cohort,
      few were associated with incident cataract. However, with the high frequency of
      use of medications and the possibility that effects of current exposure may occur
      in the future, it is reasonable to follow this and other older cohorts for the
      development of cataract.

PMID- 11535473
TI  - Phacoemulsification in patients after allogeneic bone marrow transplantation.
AB  - OBJECTIVE: To study the outcomes of phacoemulsification in allogeneic bone marrow
      transplant (allo-BMT) recipients. DESIGN: Retrospective, noncomparative,
      interventional case series. METHODS: Retrospective study of 34 eyes of 19
      consecutive patients who had visually significant cataracts after allo-BMT and
      subsequently underwent phacoemulsification. MAIN OUTCOME MEASURES: Best-corrected
      vision at the last follow-up visit and development of postoperative
      complications. RESULTS: Surgery was done at a mean interval of 37 months after
      BMT, and the mean postoperative follow-up was 13 months. Twenty-one eyes (62%)
      had subnormal Schirmer I scores as a result of graft-versus-host disease (GVHD)
      involving the lacrimal gland. Of these, 71% (15 eyes) additionally had
      significant ocular surface epitheliopathy because of conjunctival GVHD. Frequent
      lubrication (95%), punctal occlusion (76%), topical steroids (33%), and other
      topical immunosuppressive therapies (14%) were used to manage GVHD-induced ocular
      surface disease before cataract surgery. Twelve patients (63%) also received
      systemic steroids and immunosuppressives. Patients proceeded to surgery only
      after their ocular surface disease was well controlled. Early postoperative
      complications included intraocular pressure elevation (three eyes), worsening of
      dry eye syndrome (two eyes), and corneal thinning (one eye). Posterior capsular
      opacification (PCO) requiring laser capsulotomy occurred in 44% of eyes. In eyes
      with preoperative conjunctival GVHD, 47% had recurrence with cessation of
      immunosuppressive therapy after surgery. Visual acuity at last follow-up visit
      was 20/30 or better in 33 (97%) eyes. CONCLUSIONS: Phacoemulsification is an
      effective procedure in restoring vision in patients who have cataracts develop
      after BMT. However, coexisting ocular disease must be recognized and aggressively
      treated both before and after surgery to ensure good visual outcomes.

PMID- 11535474
TI  - Two-year outcomes of intrastromal corneal ring segments for the correction of
      myopia.
AB  - OBJECTIVE: To evaluate the safety and efficacy of Intrastromal Corneal Ring
      Segments (ICRS) for the correction of myopia. DESIGN: Nonrandomized, comparative
      trial. PARTICIPANTS: Patients enrolled in the United States Food and Drug
      Administration phase II and phase III clinical trials of the ICRS had best
      spectacle-corrected visual acuity (BSCVA) of 20/20 or better, myopia of -1.00 to 
      3.50 diopters (D), and a cylindrical correction of 1.00 D or less as measured by
      manifest refraction. INTERVENTION: Surgical correction of myopia with an ICRS.
      MAIN OUTCOME MEASURES: Efficacy was assessed by predictability of refractive
      outcome (deviation from predicted cycloplegic refraction spherical equivalent),
      stability of refractive effect, and postoperative uncorrected visual acuity.
      Safety was assessed by adverse events, maintenance or loss of preoperative BSCVA,
      and induced manifest refraction cylinder. RESULTS: Four hundred fifty-two
      patients were enrolled at 11 investigational sites in both studies. Of the 454
      surgical attempts, 449 received an ICRS in one eye (0.25, 0.30, and 0.35 mm in
      148, 151, and 150 eyes, respectively). First surgeries were attempted in 452
      patients. An ICRS was successfully implanted in 447 initial eyes, and 5 surgeries
      were discontinued. Of the five discontinued surgeries, three patients
      subsequently exited from the study, and two patients went on to have the ICRS
      implanted in the second eye, bringing the total number of successful implants to
      449 patient eyes. Month 24 postoperative follow-up was completed on 358 patients
      (80%). At month 24, 328 of 354 eyes (93%) were within +/-1.00 D of predicted
      refractive outcome. Refraction changed by 1 D or less in 97% of eyes (421/435)
      between 3 and 6 months after implantation and in 99% (343/348) between months 18
      and 24. Before surgery, 87% of eyes (390/448) saw worse than 20/40 uncorrected;
      24 months after surgery, 55% of eyes (196/358) saw 20/16 or better, 76% (271/358)
      saw 20/20 or better, and 97% (346/358) saw 20/40 or better. Although two eyes
      (2/358; 0.5%) lost two or more lines of BSCVA at 24 months; visual acuity in both
      was 20/20 or better. Intraoperative complications included anterior corneal
      surface perforation (three eyes) and anterior chamber perforations (two eyes, one
      during an attempted exchange procedure); all healed spontaneously without
      suturing and without loss of BSCVA. The ICRS was repositioned in five eyes to
      increase correction. Postoperative complications in one eye each were infectious
      keratitis, shallow segment placement, and loss of two lines of BSCVA at two or
      more consecutive examinations (subsequently regained). CONCLUSIONS: The ICRS
      safely, predictably, and effectively reduced or eliminated myopia of -1.00 to 
      3.50 D. The refractive effect was stable over time.

PMID- 11535475
TI  - Topography-driven excimer laser for the retreatment of decentralized myopic
      photorefractive keratectomy.
AB  - OBJECTIVE: This study evaluated the efficacy, predictability, stability, and
      safety of a software program (Corneal Interactive Programmed Topographic
      Ablation, CIPTA, LIGI, Taranto, Italy), which, by transferring programmed
      ablation from the corneal topograph to a flying-spot excimer laser, provides
      customized laser ablation for correction of postmyopic photorefractive
      keratectomy (PRK) decentrations. DESIGN: Noncomparative consecutive case series.
      PARTICIPANTS: Thirty-two eyes of 32 subjects with a mean age of 35 years (range,
      19-49; standard deviation [SD], 7.9) had CIPTA-guided PRK at the Clinica
      Oculistica of Bari University (Italy). All the subjects had irregular astigmatism
      after postmyopic PRK because of clinically significant, decentered treatments of
      more than 1 mm. OPERATION: Individual topographies were acquired by a corneal
      topograph (Orbscan II, Orbtek, Inc., Salt Lake City, UT). These, together with
      refractive data, were processed to obtain a customized altimetric ablation
      profile that was transferred to a flying-spot laser (Laserscan 2000, Lasersight,
      Orlando, FL). MAIN OUTCOME MEASURES: The topographic study of centration and data
      on uncorrected (UCVA) and best-corrected (BCVA) visual acuity, predictability,
      and stability of refraction, and any complications, were analyzed. RESULTS: Mean
      follow-up was 10.3 months (range, 4-18 months; SD, 5.8). At the last
      postoperative examination, 29 eyes (90.6%) had a UCVA superior to 20/40. Nineteen
      eyes (59.4%) had a UCVA of 20/20. Twenty-two eyes (68.75%) were within 0.50
      diopters (D) of attempted correction in the spherical equivalent and 28 eyes
      (87.5%) were within 1 D. The index of success of astigmatic correction was 0.15.
      No eye lost Snellen lines of BCVA, whereas 18 eyes (56.25%) gained Snellen lines.
      Postoperative topographies revealed well-centered treatments. CONCLUSIONS: The
      combination of topographic data with computer controlled flying-spot excimer
      laser ablation is a suitable solution for correcting irregular astigmatism after
      postmyopic PRK decentrations.

PMID- 11535476
TI  - Intracameral anesthesia: a report by the American Academy of Ophthalmology.
AB  - OBJECTIVE: This document describes the technique of intracameral anesthesia and
      examines the available evidence to address questions about its effectiveness,
      possible corneal endothelial and retinal toxicity, and the optimal and maximal
      dose. METHODS: A literature search conducted for the years 1968 to 2000 retrieved
      over 180 citations that matched the search criteria. Panel members and a
      methodologist reviewed this information, and it was evaluated for the quality of
      the evidence presented. RESULTS: Some studies report effectiveness of
      intracameral anesthesia while others report no effect. In those studies showing
      an effect, levels of pain in the groups that were compared were low. Short-term
      studies seem to indicate that preservative (methylparaben)-free lidocaine 1% is
      well tolerated by the corneal endothelium but that higher concentrations of
      lidocaine are toxic. There is some evidence of electroretinogram changes after
      exposure to lidocaine or bupivacaine. CONCLUSIONS: The ideal timing and placement
      of intracameral anesthesia has not been determined. Because topical anesthesia
      alone is effective, surgeons may elect to use intracameral anesthesia for
      incremental pain control in patients who cannot be adequately managed with
      topical alone. Appropriate patient selection is important when using this method
      of anesthesia. While short-term studies seem to indicate safety, long-term
      effects are unknown. Patient preferences for anesthesia are not well studied.

PMID- 11535477
TI  - Utility of an initial D-dimer assay in screening for traumatic or spontaneous
      intracranial hemorrhage.
AB  - OBJECTIVE: To evaluate the sensitivity of a D-dimer assay as a screening tool for
      possible traumatic or spontaneous intracranial hemorrhage. If adequately
      sensitive, the D-dimer assay may potentially permit omission of a more expensive
      computed tomography (CT) scan of the head when such hemorrhage is clinically
      suspected. METHODS: Prospective, consecutive, blinded study of patients (age > 16
      years) requiring a CT scan of the head for suspected intracranial hemorrhage over
      a five-month period at a university, Level I trauma center. All study patients
      had a serum D-dimer assay obtained prior to their CT scans. Sensitivity and
      specificity, with 95% confidence intervals (95% CIs), of the enzyme-linked
      immunosorbent assay (ELISA) D-dimer assay for the detection of intracranial
      hemorrhage were calculated. RESULTS: Of the 319 patients entered in the study, 25
      (7.8%) had a CT scan positive for intracranial hemorrhage. Patients with
      intracranial hemorrhage were more likely to have a positive D-dimer assay (chi
      square = 13.075, p < 0.001). The D-dimer assay had 21 true-positive and four
      false-negative tests, resulting in a sensitivity of 84.0% (95% CI = 63.7% to
      95.5%) and a specificity of 55.8% (95% CI = 55.5% to 55.9%). The four false
      negative cases included one small intraparenchymal hemorrhage, one small
      subarachnoid hemorrhage, one moderate-sized intraparenchymal hemorrhage with mid
      line shift, and one large subdural hematoma requiring emergent surgery.
      CONCLUSIONS: Due to the catastrophic nature of missing an intracranial hemorrhage
      in the emergency department, the D-dimer assay is not adequately sensitive or
      predictive to use as a screening tool to allow routine omission of head CT
      scanning.

PMID- 11535478
TI  - Epidemiology of thoracolumbar spine injury in blunt trauma.
AB  - OBJECTIVE: To evaluate the prevalence, distribution, and demographics of
      thoracolumbar (TL) spine injuries following blunt trauma. METHODS: Prospective,
      cross-sectional study of a consecutive sample of all blunt trauma patients
      presenting initially to the emergency department (ED) of a Level 1 trauma center
      and undergoing thoracic and/or lumbar spine radiography from August 1997 to
      November 1998. The age, sex, and mechanism of injury of each patient as well as
      location and type of spine injury were recorded for those patients with vertebral
      fractures, dislocations, or subluxations. RESULTS: Two thousand four hundred four
      blunt trauma patients were enrolled. Vertebral injuries were identified in 152
      individuals (6.3%, 95% CI = 5.4% to 7.4%). Two hundred sixty distinct anatomic
      levels of injury were identified in these 152 individuals. Of these 260 injuries,
      42 (16.2%) occurred at L1, 38 (14.6%) at L2, 29 (11.1%) at L3, and 27 (10.4%) at
      T12, making these the most commonly injured vertebrae. Injuries were most common
      (34 patients) in those aged 30-39 years and were least common (12 patients) in
      those under 18 years. Compression fractures (52%) were the most common injury in
      the thoracic spine, while transverse process fractures (48%) were the most common
      injuries in the lumbar spine. CONCLUSIONS: The prevalence of TL injuries in ED
      blunt trauma patients undergoing TL radiographs is 6.3%. The most commonly
      injured area of the TL spine is the thoracolumbar junction.

PMID- 11535479
TI  - Droperidol vs. prochlorperazine for benign headaches in the emergency department.
AB  - OBJECTIVE: To compare the efficacy of droperidol with that of prochlorperazine
      for the treatment of benign headaches in emergency department (ED) patients.
      METHODS: Prospective, randomized clinical trial in an urban ED. Patients were
      given either droperidol, 5 mg intramuscular (IM) or 2.5 mg intravenous (IV), or
      prochlorperazine, 10 mg IM or 10 mg IV. Measurements included side effects and
      the patient's pain perception as measured on a 100-mm visual analog scale (VAS)
      at baseline, 30, and 60 minutes after the medication was given. Data were
      analyzed using chi-square, two-tailed t-tests, and two-way analysis of variance
      (ANOVA) when appropriate. RESULTS: During an eight-month period, 168 patients
      were enrolled. Eighty-two (48.8%) of the patients received droperidol; 86 (51.2%)
      received prochlorperazine. In the droperidol group, 49 (59.6%) received IM
      administration and 33 (40.4%) IV. In the prochlorperazine group, 57 (66.3%)
      received IM administration and 29 (33.7%) IV. Sixty minutes after the medication,
      the mean decrease in the VAS scores was 81.4% for droperidol and 66.9% for
      prochlorperazine (p = 0.001). At 30 minutes, 60.9% of the patients receiving
      droperidol and 44.2% of the patients receiving prochlorperazine had obtained at
      least a 50% reduction in their VAS scores (p = 0.09). At 60 minutes, 90.2% of the
      patients receiving droperidol and 68.6% of the patients receiving
      prochlorperazine had at least a 50% reduction in their VAS scores (p = 0.017). No
      difference between IM dosing and IV dosing was detected. Side effects, including
      dystonia, akathisia, and decreased level of consciousness, were seen in 15.2% of
      the patients receiving droperidol and 9.61% of the patients receiving
      prochlorperazine. No significant or persisting morbidity was detected.
      CONCLUSIONS: Droperidol was more effective than prochlorperazine in relieving
      pain associated with benign headaches.

PMID- 11535480
TI  - The impact of changes in HCFA documentation requirements on academic emergency
      medicine: results of a physician survey.
AB  - BACKGROUND: The Health Care Financing Administration (HCFA) has dramatically
      increased documentation and procedural supervision required by faculty in
      academic emergency departments (EDs). OBJECTIVES: To determine academic emergency
      medicine (EM) physicians' perceptions of the impact of HCFA documentation
      requirements (HDR) on teaching time, clinical efficiency, and job satisfaction.
      METHODS: An observational cross-sectional study was done using a survey of New
      England academic EM faculty from September to December 1999. E-mail surveys were
      followed by hard copy to nonresponders. Teaching time, clinical efficiency, and
      job satisfaction were rated on a five-point Likert scale. Yes/no questions about
      other possible benefits of HCFA regulations were asked. Frequency (95% CI) and
      chi-square analyses were performed. RESULTS: One hundred seventy-four of 233
      (75%) responded. Eighty-nine percent (95% CI = 84% to 93%) of the respondents
      thought teaching time was somewhat or markedly decreased by changes in HDR
      (somewhat 46%, markedly 43%). Seventy-nine percent (95% CI = 73% to 85%) believed
      clinical efficiency was somewhat or markedly decreased by changes in HDR
      (somewhat 49%, markedly 30%). Eighty percent (95% CI = 73% to 86%) reported
      somewhat or markedly decreased job satisfaction due to changes in HDR (somewhat
      56%, markedly 24%). Twenty-one percent (95% CI = 15% to 27%) believed changes in
      HDR had improved patient care by requiring increased patient supervision. Forty
      eight percent (95% CI = 40% to 56%) thought that changes in documentation
      requirements had decreased medicolegal risk by improving patient documentation.
      CONCLUSIONS: Most academic EM physicians in New England perceive that HDR have
      decreased clinical efficiency, teaching time, and job satisfaction. These
      findings suggest that changes in HDR may have a substantial impact on many
      different aspects of emergency care provided in academic settings.

PMID- 11535481
TI  - Doing unto others? Emergency medicine residents' willingness to be treated by
      moonlighting residents and nonphysician clinicians in the emergency department.
AB  - OBJECTIVE: Contentious moonlighting policies and the proliferation of
      nonphysician clinicians (NPCs) in academic emergency departments (EDs) send
      conflicting messages to emergency medicine (EM) residents regarding appropriate
      ED staffing patterns. The objective was to assess EM resident (EMR) views on the
      ED utilization of unsupervised residents and NPCs from their perspectives as both
      physicians and prospective patients. METHODS: A survey was mailed to a random
      sample of senior EMRs (sampling fraction, 68%) from the Emergency Medicine
      Residents Association membership list. Respondents were instructed to assume the
      role of patient when presented with hypothetical clinical scenarios of increasing
      severity; outcomes included provider preferences and the impacts of medical
      urgency, time delays, costs, and supervision on those preferences. Survey items
      asked about willingness to see residents, nurse practitioners (CRNPs), and
      physician assistants (PAs), and perceived impact of NPCs on professional
      identity. RESULTS: A total of 251 EMRs responded. Senior EMRs are more willing to
      have their care handled by residents as opposed to mid-level providers. For a
      moderate illness or injury scenario, 54% agreed to be seen by a resident alone
      compared with only 17% and 24% willing to be seen by a CRNP and PA, respectively.
      Only a small fraction of the residents (22.7%) would allow another resident to
      treat them for a major injury or illness. Residents are more willing to be seen
      by mid-level providers if a savings in time can be realized but showed little
      interest in using NPCs to save money. Approximately one-third (34%) of the
      residents view mid-level providers as a professional threat, but logistic
      regression reveals this perception to be 2.25 (1.3, 4.0) times higher in male
      EMRs and 1.94 (1.1, 3.4) times higher in those with higher household incomes (>
      or =$75,000). CONCLUSIONS: When assuming the patient role, senior EMRs have
      preferences for ED care that are consistent with restrictive EMR moonlighting and
      NPC staffing policies.

PMID- 11535482
TI  - Clinical pearls: struck by lightning. Cutaneous manifestation of lightning strike
      ("splash").

PMID- 11535483
TI  - Using conjoint analysis to assess patients' preferences when visiting emergency
      departments in Hong Kong.
AB  - OBJECTIVES: To explore factors related to emergency department (ED) attendances
      in Hong Kong, the authors piloted the application of conjoint analysis in
      eliciting patient preferences regarding ED visits. METHODS: The study recruited
      390 semi-urgent or non-urgent patients from a targeted convenience sample of
      three large EDs. Respondents were asked to rank eight scenarios structured to
      explore the relative importance of three key attributes-self-perceived illness
      severity, waiting time, and consultation fee-that may result in an ED visit.
      RESULTS: Seventy-eight percent of the respondents would consider visiting a
      parallel clinic instead of the ED for semi-urgent and non-urgent conditions. The
      relative importance attached to illness severity, waiting time, and consultation
      fee were 47.8%, 33.6%, and 18.7%, respectively. CONCLUSIONS: This study
      demonstrated that Hong Kong patients are receptive to the concept of parallel
      clinics, and illustrated that conjoint analysis is a rigorous survey technique
      for eliciting the views of patients on health care services in the ED setting.

PMID- 11535484
TI  - SAEM-state of the society, 2001. Society for Academic Emergency Medicine.

PMID- 11535485
TI  - AEM-state of the journal, 2001. Academic emergency medicine.

PMID- 11535486
TI  - Change is hard-physician behavior and documentation guidelines.

PMID- 11535487
TI  - Bench to bedside: resuscitation from prolonged ventricular fibrillation.
AB  - Ventricular fibrillation (VF) remains the most common cardiac arrest heart
      rhythm. Defibrillation is the primary treatment and is very effective if
      delivered early within a few minutes of onset of VF. However, successful
      treatment of VF becomes increasingly more difficult when the duration of VF
      exceeds 4 minutes. Classically, successful cardiac arrest resuscitation has been
      thought of as simply achieving restoration of spontaneous circulation (ROSC).
      However, this traditional approach fails to consider the high early post-cardiac
      arrest mortality and morbidity and ignores the reperfusion injuries, which are
      manifest in the heart and brain. More recently, resuscitation from cardiac arrest
      has been divided into two phases; phase I, achieving ROSC, and phase II,
      treatment of reperfusion injury. The focus in both phases of resuscitation
      remains the heart and brain, as prolonged VF remains primarily a two-organ
      disease. These two organs are most sensitive to oxygen and substrate deprivation
      and account for the vast majority of early post-resuscitation mortality and
      morbidity. This review focuses first on the initial resuscitation (achieving
      ROSC) and then on the reperfusion issues affecting the heart and brain.

PMID- 11535488
TI  - Preventive care in the emergency department: a systematic literature review on
      emergency department-based interventions that address smoke detectors in the
      home.
AB  - OBJECTIVES: To assess the effectiveness of an emergency department (ED)-based
      strategy to identify and counsel selected patients about the importance of an
      operational smoke detector in the home and to offer a graded recommendation
      regarding such a strategy. METHODS: A systematic review was facilitated through
      the use of a structured template, a companion explanatory piece, and a grading
      and methodological scoring system based on published criteria for critical
      appraisal. Two Medline combined searches were performed using the following
      terms: emergency medical services and counseling, protective devices and smoke
      detectors, accidents, home, burns, fires, and residential fires. A free-text
      search of indexed and nonindexed citations in Emergency Medical Abstracts from
      1977 to 1999 and a search of the Cochrane Library were also performed. In
      addition, reviewers performed independent Medline searches and suggested four
      additional studies. Studies selected for inclusion in this systematic review were
      required to meet the following criteria: 1) report ED-based research and 2)
      address the topic of fire and burn prevention with some pertinent discussion of
      ED-based interventions. The initial inclusion criteria had restricted studies to
      those that reported the results of counseling strategies for smoke detectors. The
      authors later decided to consider, as indirectly relevant, studies that did not
      investigate counseling strategies. Data from the selected studies were extracted
      using the template form, and the validity and applicability of the results to
      emergency practice were assessed. Recommendations were derived following criteria
      developed by a systematic review of preventive interventions in the ED. RESULTS:
      Six articles were closely reviewed. Four of the six studies met the inclusion
      criteria. One other study that did not meet the inclusion criteria was also
      considered. No study focused specifically on the counseling of ED patients about
      smoke detectors. CONCLUSIONS: Following the criteria of the graded
      recommendations used for the parent project. a recommendation cannot be made
      either for or against an ED-based strategy to counsel patients on the importance
      of smoke detectors. No studies located in our review directly assessed the
      effectiveness of such a strategy. Based on the retrospective case series study of
      the potential opportunity for a home fire safety intervention during an emergency
      medical services visit and the Safe Block Project study, it may be worthwhile to
      consider further research on the effectiveness of systems-level/structural
      interventions, with a targeted focus on strategies that attempt to overcome
      barriers associated with active interventions.

PMID- 11535489
TI  - Are emergency department patients at risk for herb-drug interactions?
AB  - OBJECTIVES: To determine the prevalence of herbal and/or dietary supplement use
      and identify patients at risk for herb-drug interactions. METHODS: A convenience
      sample of 944 patients were surveyed to determine the prevalence and types of
      supplements used. Patients with heart disease, diabetes, psychiatric disorders,
      and/or hypertension were assessed for potential interactions. RESULTS: One
      hundred thirty-five (14.3%) patients reported regular use. Of these, 79.3% were
      taking supplements concurrently with prescription medications, and 80.0% were
      administered medication(s) in the emergency department. Cardiac: 19.8% (n = 33)
      reported regular use, with four potential interactions. Hypertension: 20.3% (n =
      54) reported regular use, with two potential interactions. Diabetes: 15.9% (n =
      20) reported regular use, with no known interactions. Psychiatric: 15.9% (n = 10)
      reported regular use, with one potential interaction. CONCLUSIONS: Six patients
      were identified at risk for seven known herb-drug interactions. The prevalence of
      undisclosed herbal supplement use and lack of research on these supplements
      suggest that more patients may be at risk.

PMID- 11535493
TI  - Dynamic molecular modeling of pathogenic mutations in the spectrin self
      association domain.
AB  - Disruption of spectrin self-association underlies many inherited hemolytic
      disorders. Using dynamic modeling and energy minimization, the 3-dimensional
      structure of the self-association domain has been estimated in human erythrocyte
      spectrin and the structural consequences of 17 elliptogenic mutations determined.
      The predicted structure of the normal self-association domain was remarkably
      similar to the crystal structure of the Drosophila alpha-spectrin 14th repeat
      unit, despite replacement in the human sequence of over 70% of the amino acids
      relative to fly spectrin, including 2 prolines in the human sequence that appear
      in helical regions of the fly structure. The predicted structure placed all
      hydrophilic residues at the surface and identified 4 salt bridges, 9 hydrophobic
      interactions, and 4 H-bonds that stabilize the native self-association unit.
      Remarkably, every pathologic point mutation, including seemingly conservative
      substitutions such as G for A, A for V, or K for R (single-letter amino acid
      codes), led to conformational rearrangements in the predicted structure. The
      degree of structural disruption, as measured by root-mean-square deviation of the
      predicted backbone structure from the Drosophila structure, correlated strongly
      with the severity of clinical disease associated with each mutation. This
      approach thus enables an accurate prediction, from the primary sequence, of the
      clinical consequences of specific point mutations in spectrin. The 3-dimensional
      structure of the self-association domain derived here is likely to be accurate.
      It provides a powerful heuristic model for understanding how point mutations
      disrupt cytoskeletal function in a variety of hemolytic disorders.

PMID- 11535494
TI  - Partial amino acid sequence of purified von Willebrand factor-cleaving protease.
AB  - von Willebrand factor-cleaving protease (vWF-cp) is responsible for the
      continuous degradation of plasma vWF multimers released from endothelial cells.
      It is deficient in patients with thrombotic thrombocytopenic purpura, who show
      unusually large vWF multimers in plasma. Purified vWF-cp may be useful for
      replacement in these patients, who are now treated by plasma therapy. In this
      study, vWF-cp was purified from normal human plasma by affinity chromatography on
      the IgG fraction from a patient with autoantibodies to vWF-cp and by a series of
      further chromatographic procedures, including affinity chromatography on Protein
      G, Ig-TheraSorb, lentil lectin, and heparin. Four single-chain protein bands,
      separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under
      nonreducing conditions, showed M(r) of 150, 140, 130, and 110 kd and were found
      to share the same N-terminal amino acid sequence, suggesting that they were
      derived from the same polypeptide chain that had been partially degraded at the
      carboxy-terminal end. A hydrophobic sequence (Ala-Ala-Gly-Gly-Ile-Leu-His-Leu-Glu
      Leu-Leu-Val-Ala-Val-Gly) of the first 15 residues was established. The protease
      migrates in gel filtration as a high-molecular-weight complex with clusterin, a
      70-kd protein with chaperonelike activity. vWF-cp bound to clusterin is
      dissociated by the use of concentrated chaotropic salts. vWF-cp in normal human
      plasma or serum is not associated with clusterin, suggesting that the observed
      complex is due to vWF-cp denaturation during the purification procedure. Activity
      of vWF-cp is unusually stable during incubation at 37 degrees C; its in vitro
      half-life in citrated human plasma, heparin plasma, or serum is longer than 1
      week. There was even a temporary increase in protease activity during the first 3
      days of incubation.

PMID- 11535495
TI  - Purification of human von Willebrand factor-cleaving protease and its
      identification as a new member of the metalloproteinase family.
AB  - von Willebrand factor (vWF) is synthesized in megakaryocytes and endothelial
      cells as a very large multimer, but circulates in plasma as a group of multimers
      ranging from 500 to 10 000 kd. An important mechanism for depolymerization of the
      large multimers is the limited proteolysis by a vWF-cleaving protease present in
      plasma. The absence or inactivation of the vWF-cleaving protease results in the
      accumulation of large multimers, which may cause thrombotic thrombocytopenic
      purpura. The vWF-cleaving protease was first described as a Ca(++)-dependent
      proteinase with an apparent molecular weight of approximately 300 kd. Thus far,
      however, it has not been isolated and characterized. In this study, the
      purification of human vWF-cleaving protease from a commercial preparation of
      factor VIII/vWF concentrate by means of several column chromatographic steps,
      including 2 steps of heparin-Sepharose column, is reported. Sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis analysis of the anion exchange and gel
      filtration column fractions showed that the vWF-cleaving protease activity
      corresponded to a protein band of 150 kd. After reduction, it migrated with an
      apparent weight of 190 kd. The amino terminal sequence of the 150-kd band was
      AAGGIL(H)LE(L)L(D)AXG(P)X(V)XQ (single-letter amino acid codes), with the
      tentative residues shown in parentheses. A search of the human genome sequence
      identified the vWF-cleaving protease as a new member of the ADAMTS (a disintegrin
      and metalloproteinase with thrombospondin type I motif) family of
      metalloproteinase. An active site sequence of HEIGHSFGLEHE (single-letter amino
      acid codes) was located at 150 residues from the N terminus of the protein.

PMID- 11535496
TI  - Dressed to kill? A review of why antiviral CD8 T lymphocytes fail to prevent
      progressive immunodeficiency in HIV-1 infection.
AB  - CD8 T cells play an important role in protection and control of HIV-1 by direct
      cytolysis of infected cells and by suppression of viral replication by secreted
      factors. However, although HIV-1-infected individuals have a high frequency of
      HIV-1-specific CD8 T cells, viral reservoirs persist and progressive
      immunodeficiency generally ensues in the absence of continuous potent antiviral
      drugs. Freshly isolated HIV-specific CD8 T cells are often unable to lyse HIV-1
      infected cells. Maturation into competent cytotoxic T lymphocytes may be blocked
      during the initial encounter with antigen because of defects in antigen
      presentation by interdigitating dendritic cells or HIV-infected macrophages. The
      molecular basis for impaired function is multifactorial, due to incomplete T-cell
      signaling and activation (in part related to CD3zeta and CD28 down-modulation),
      reduced perforin expression, and inefficient trafficking of HIV-specific CD8 T
      cells to lymphoid sites of infection. CD8 T-cell dysfunction can partially be
      corrected in vitro with short-term exposure to interleukin 2, suggesting that
      impaired HIV-specific CD4 T helper function may play a significant causal or
      exacerbating role. Functional defects are qualitatively different and more severe
      with advanced disease, when interferon gamma production also becomes compromised.

PMID- 11535497
TI  - Deregulation of the expression of the fractalkine/fractalkine receptor complex in
      HIV-1-infected patients.
AB  - Fractalkine is the only member of the CX3C chemokine family. Polymorphism of the
      fractalkine receptor gene may influence the prognosis of human immunodeficiency
      virus (HIV) infection, but the nature of the cells expressing fractalkine or its
      receptor in HIV-infected patients remains unknown. We show that, in contrast to
      HIV-uninfected individuals, a large number of cells expressed fractalkine in T
      cell zones of lymph nodes from HIV-infected patients. CD83(+) mature and CD123(+)
      plasmacytoid dendritic cells as well as plasma cells are involved in this
      increased expression of fractalkine. Increased numbers of plasmacytoid dendritic
      cells and plasma cells were present in T-cell zones of HIV-infected patients.
      CD83(+) dendritic cells were present in similar number in HIV-infected patients
      and controls, but an increased fraction of these cells produced fractalkine in
      HIV-infected patients. Many plasma cells in the gut-associated lymphoid tissue
      from HIV-infected patients also produced fractalkine, whereas few cells produced
      fractalkine in the gut of controls. The fraction of CD45RO(+) and CD45RO(-) T
      helper (Th) cells expressing the fractalkine receptor CX3CR1 was higher in HIV
      infected patients than in healthy individuals, and these cells were abnormally
      sensitive to fractalkine stimulation. This increased response correlated with HIV
      viremia, and it returned to normal levels in patients successfully treated with
      antiretroviral drugs. The increased expression of the fractalkine/fractalkine
      receptor complex associated with HIV infection may affect adhesion and migration
      of Th lymphocytes and their interaction with dendritic cells. Thus, it may
      influence the equilibrium between depletion and renewal of the Th lymphocyte
      compartment.

PMID- 11535498
TI  - Delayed donor red cell chimerism and pure red cell aplasia following major ABO
      incompatible nonmyeloablative hematopoietic stem cell transplantation.
AB  - Delayed donor red cell engraftment and pure red cell aplasia (PRCA) are well
      recognized complications of major ABO-incompatible hematopoietic stem cell
      transplantation (SCT) performed by means of myeloablative conditioning. To
      evaluate these events following reduced-intensity nonmyeloablative SCT (NST),
      consecutive series of patients with major ABO incompatibility undergoing either
      NST (fludarabine/cyclophosphamide conditioning) or myeloablative SCT
      (cyclophosphamide/high-dose total body irradiation) were compared. Donor red
      blood cell (RBC) chimerism (initial detection of donor RBCs in peripheral blood)
      was markedly delayed following NST versus myeloablative SCT (median, 114 versus
      40 days; P <.0001) and strongly correlated with decreasing host antidonor
      isohemagglutinin levels. Antidonor isohemagglutinins declined to clinically
      insignificant levels more slowly following NST than myeloablative SCT (median, 83
      versus 44 days; P =.03). Donor RBC chimerism was delayed more than 100 days in 9
      of 14 (64%) and PRCA occurred in 4 of 14 (29%) patients following NST, while
      neither event occurred in 12 patients following myeloablative SCT. Conversion to
      full donor myeloid chimerism following NST occurred significantly sooner in cases
      with, compared with cases without, PRCA (30 versus 98 days; P =.008).
      Cyclosporine withdrawal appeared to induce graft-mediated immune effects against
      recipient isohemagglutinin-producing cells, resulting in decreased antidonor
      isohemagglutinin levels and resolution of PRCA following NST. These data indicate
      that significantly delayed donor erythropoiesis is (1) common following major ABO
      incompatible NST and (2) associated with prolonged persistence of host antidonor
      isohemagglutinins. The clinical manifestations of these events are affected by
      the degree and duration of residual host hematopoiesis.

PMID- 11535499
TI  - Chronic graft-versus-host disease after allogeneic blood stem cell
      transplantation.
AB  - The incidence, characteristics, risk factors for, and impact of chronic graft-vs
      host disease (GVHD) were evaluated in a consecutive series of 116 evaluable HLA
      identical blood stem cell transplant recipients. Minimum follow-up was 18 months.
      Limited chronic GVHD occurred in 6% (95% confidence interval [CI], 0%-13%), and
      clinical extensive chronic GVHD in 71% (95% CI, 61%-80%). The cumulative
      incidence was 57% (95% CI, 48%-66%). In univariate analyses, GVHD prophylaxis
      other than tacrolimus and methotrexate, prior grades 2 to 4 acute GVHD, use of
      corticosteroids on day 100, and total nucleated cell dose were significant risk
      factors for clinical extensive chronic GVHD. On multivariate analysis, GVHD
      prophylaxis with tacrolimus and methotrexate was associated with a reduced risk
      of chronic GVHD (hazard ratio [HR], 0.35; P =.001), whereas the risk was
      increased with prior acute GVHD (HR, 1.67; P =.046). When adjusted for disease
      status at the time of transplantation, high-risk chronic GVHD had an adverse
      impact on overall mortality (HR, 6.6; P <.001) and treatment failure (HR, 5.2; P
      <.001) at 18 months. It was concluded that there is a substantial rate of chronic
      GVHD after HLA-identical allogeneic blood stem cell transplantation, that
      clinical factors may alter the risk of chronic GVHD, and that high-risk chronic
      GVHD adversely affects outcome.

PMID- 11535500
TI  - The significance of bcr-abl molecular detection in chronic myeloid leukemia
      patients "late," 18 months or more after transplantation.
AB  - The bcr-abl chimeric messenger RNA is frequently detected in chronic myeloid
      leukemia (CML) patients after bone marrow transplantation. It was previously
      reported that the relapse risk of bcr-abl detection 6 to 12 months after
      transplantation was greater than 40%. This risk decreased as the time between
      transplantation and detection increased. To further define the relapse risk
      associated with bcr-abl molecular detection in "late" CML survivors, 379
      consecutive CML patients alive at 18 months after transplantation or later were
      studied. Ninety of 379 patients (24%) had at least one positive bcr-abl test 18
      months after transplantation or later; 13 of 90 bcr-abl-positive patients (14%)
      and 3 of 289 bcr-abl-negative patients (1.0%) relapsed. The median time from bcr
      abl detection to relapse was 916 days (range, 251-2654 days). The hazard ratio of
      relapse associated with bcr-abl detection was 19.2 (P <.0001). The stage of
      disease, chronic graft-versus-host disease, and the donor type did not alter the
      association between bcr-abl and relapse. Quantification of bcr-abl was performed
      on 344 samples from 85 bcr-abl-positive patients by means of a real-time
      quantitative reverse transcriptase-polymerase chain reaction assay. The median
      bcr-abl change of patients who relapsed was significantly greater than those that
      remained in remission (P =.002). The median bcr-abl level at relapse was 40 443
      bcr-abl copies per microg RNA (range, 960-299 552). Of 73 bcr-abl-positive
      patients who failed to relapse, 69% had only one positive test at a median of 24
      copies bcr-abl per microg RNA. The detection of bcr-abl is common following
      transplantation. The prognostic significance of a qualitative bcr-abl can be
      refined by quantitative assays and thus may target patients who would benefit
      from early intervention.

PMID- 11535501
TI  - Phase 1 study of polyethylene glycol formulation of interferon alpha-2B (Schering
      54031) in Philadelphia chromosome-positive chronic myelogenous leukemia.
AB  - Interferon alpha (IFN-alpha) therapy improves prognosis in Philadelphia
      chromosome (Ph)-positive chronic myelogenous leukemia (CML). Polyethylene glycol
      (PEG) attached to IFN-alpha prolongs its half-life and may offer better therapy.
      The aims of this phase 1 study were to define the maximal tolerated dose (MTD),
      dose-limiting toxicities (DLTs), and response with PEG IFN-alpha-2b. Twenty-seven
      adults with Ph(+) CML in chronic or accelerated phases, in whom IFN-alpha
      treatment had failed, were studied. Patients had hematologic (9 patients) or
      cytogenetic resistance (12 patients) or intolerance to IFN-alpha (6 patients).
      PEG IFN-alpha-2b was given as a weekly subcutaneous injection starting at 0.75
      microg/kg weekly and escalating to 1.5, 3, 4.5, 6, 7.5, and 9.0 microg/kg. The
      MTD was defined at 7.5 to 9 microg/kg; DLT included severe fatigue,
      neurotoxicity, liver function abnormalities, and myelosuppression. Longer
      administration of PEG IFN-alpha-2b resulted in chronic side effects not observed
      earlier, which defined the MTD and DLT. The proposed phase 2 dose of PEG IFN
      alpha-2b was 6 microg/kg weekly. Among 19 patients with active disease, 7 (37%)
      achieved complete hematologic response (CHR); 2 (11%) had a cytogenetic response
      (complete). Among 8 patients treated in CHR, 7 (87%) improved cytogenetic
      response to complete (4 patients) or partial (3 patients). All 6 patients
      intolerant to IFN-alpha tolerated PEG IFN-alpha-2b; 4 improved their cytogenetic
      response. The results show that PEG IFN-alpha-2b is easier to deliver (once
      weekly), better tolerated, and perhaps more effective than IFN-alpha.

PMID- 11535502
TI  - Relationships between age at diagnosis, clinical features, and outcome of therapy
      in children treated in the Medical Research Council AML 10 and 12 trials for
      acute myeloid leukemia.
AB  - Between May 1988 and June 2000, 698 children were treated in the Medical Research
      Council acute myeloid leukemia 10 and 12 trials. The presenting features and
      outcomes of therapy in these children were compared by age. Although there was no
      single cutoff in age, younger children were more likely to have intermediate risk
      and less likely to have favorable cytogenetics (P <.001), and they had a higher
      incidence of translocations involving chromosome 11q23 (P <.001). The
      distribution of French-American-British (FAB) types also varied with age; FAB
      types M5 (P <.001) and M7 (P <.001) were more common in early childhood, whereas
      older children were more likely to have FAB types M0 (P =.03), M1 (P =.04), M2 (P
      =.005), and M3 (P <.001). Involvement of the central nervous system at diagnosis
      was also more common in the youngest children (P =.01). Younger children had more
      severe diarrhea (P =.002), whereas older children had worse nausea and vomiting
      (P =.01) after chemotherapy. When adjusted for other important factors, complete
      remission rates were similar (P =.5) and although there was less resistant
      disease in younger children (P =.003), this was partially balanced by a slight
      increase in deaths during induction therapy in younger patients (P =.06). On
      multivariate analysis overall survival (P =.02), event-free survival (P =.02),
      and disease-free survival were better (P =.06) in younger children due to a lower
      relapse rate (P =.02) especially in the bone marrow (P =.02).

PMID- 11535503
TI  - High remission rate in T-cell prolymphocytic leukemia with CAMPATH-1H.
AB  - T-cell prolymphocytic leukemia (T-PLL) is a chemotherapy-resistant malignancy
      with a median survival of 7.5 months. Preliminary results indicated a high
      remission induction rate with the human CD52 antibody, CAMPATH-1H. This study
      reports results in 39 patients with T-PLL treated with CAMPATH-1H between March
      1993 and May 2000. All but 2 patients had received prior therapy with a variety
      of agents, including 30 with pentostatin; none achieved complete remission (CR).
      CAMPATH-1H (30 mg) was administered intravenously 3 times weekly until maximal
      response. The overall response rate was 76% with 60% CR and 16% partial remission
      (PR). These responses were durable with a median disease-free interval of 7
      months (range, 4-45 months). Survival was significantly prolonged in patients
      achieving CR compared to PR or no response (NR), including one patient who
      survived 54 months. Nine patients remain alive up to 29 months after completing
      therapy. Seven patients received high-dose therapy with autologous stem cell
      support, 3 of whom remain alive in CR 5, 7, and 15 months after autograft. Stem
      cell harvests in these patients were uncontaminated with T-PLL cells as
      demonstrated by dual-color flow cytometry and polymerase chain reaction. Four
      patients had allogeneic stem cell transplants, 3 from siblings and 1 from a
      matched unrelated donor. Two had nonmyeloablative conditioning. Three are alive
      in CR up to 24 months after allograft. The conclusion is that CAMPATH-1H is an
      effective therapy in T-PLL, producing remissions in more than two thirds of
      patients. The use of stem cell transplantation to consolidate responses merits
      further study.

PMID- 11535504
TI  - Catheter-related deep venous thrombosis in children with hemophilia.
AB  - Central venous catheters (CVCs) are a common adjunct to hemophilia therapy, but
      the risk of CVC-related deep venous thrombosis (DVT) in hemophiliacs is not well
      defined. In a previous study, 13 patients with CVCs had no radiographic evidence
      of DVT. However, recent abstracts and case studies demonstrate that DVT does
      occur. Therefore, this study sought to determine the frequency of DVT in children
      with hemophilia and long-term CVCs and to correlate venographic findings with
      clinical features. All hemophilia patients with tunneled subclavian CVCs in place
      for 12 months or more were candidates for evaluation. Patients were examined for
      physical signs of DVT and questioned about catheter dysfunction. Contrast
      venograms were obtained to identify DVT. Fifteen boys with severe hemophilia were
      evaluated, including 9 from the initially studied group of 13. Eight patients had
      evidence of DVT, 5 of whom previously had normal venograms. Five of 15 patients
      had clinical problems related to the CVC, all of whom had DVT. Four of 15
      patients had suggestive physical signs; 3 had DVT. The mean duration of catheter
      placement for all patients was 57.5 months (range, 12-102 months). For patients
      with DVT, the mean duration was 66.6 +/- 7.5 months, compared to 49.5 +/- 7.2
      months for patients without DVT (P =.06). No patient whose CVC was in place fewer
      than 48 months had an abnormal venogram. Many hemophilia patients with CVCs
      develop DVT of the upper venous system, and the risk increases with duration of
      catheter placement.

PMID- 11535505
TI  - Deletions of the derivative chromosome 9 occur at the time of the Philadelphia
      translocation and provide a powerful and independent prognostic indicator in
      chronic myeloid leukemia.
AB  - Chronic myeloid leukemia (CML) is characterized by formation of the BCR-ABL
      fusion gene, usually as a consequence of the Philadelphia (Ph) translocation
      between chromosomes 9 and 22. Large deletions on the derivative chromosome 9 have
      recently been reported, but it was unclear whether deletions arose during disease
      progression or at the time of the Ph translocation. Fluorescence in situ
      hybridization (FISH) analysis was used to assess the deletion status of 253
      patients with CML. The strength of deletion status as a prognostic indicator was
      then compared to the Sokal and Hasford scoring systems. The frequency of
      deletions was similar at diagnosis and after disease progression but was
      significantly increased in patients with variant Ph translocations. In patients
      with a deletion, all Ph(+) metaphases carried the deletion. The median survival
      of patients with and without deletions was 38 months and 88 months, respectively
      (P =.0001). By contrast the survival difference between Sokal or Hasford high
      risk and non-high-risk patients was of only borderline significance (P =.057 and
      P =.034). The results indicate that deletions occur at the time of the Ph
      translocation. An apparently simple reciprocal translocation may therefore result
      in considerable genetic heterogeneity ab initio, a concept that is likely to
      apply to other malignancies associated with translocations. Deletion status is
      also a powerful and independent prognostic factor for patients with CML. The
      prognostic significance of deletion status should now be studied prospectively
      and, if confirmed, should be incorporated into management decisions and the
      analysis of clinical trials.

PMID- 11535506
TI  - No difference in graft-versus-host disease, relapse, and survival comparing
      peripheral stem cells to bone marrow using unrelated donors.
AB  - The clinical results in 107 patients receiving a peripheral blood stem cell
      (PBSC) graft mobilized by granulocyte colony-stimulating factor (G-CSF) from HLA
      A, -B, and -DR-compatible unrelated donors were compared to 107 matched controls
      receiving unrelated bone marrow (BM) transplants. Engraftment was achieved in 94%
      of the patients in both groups. The PBSC graft contained significantly more
      nucleated cells, CD34(+), CD3(+), and CD56(+) cells (P <.001), and resulted in a
      significantly shorter time-to-neutrophil (15 versus 19 days) and platelet
      engraftment (20 versus 27 days), compared to the BM control group (P <.001).
      Probabilities of acute graft-versus-host disease (GVHD) grades II to IV were 35%
      and 32% (not significant [NS]) and of chronic GVHD 61% and 76% (NS) in the PBSC
      and BM groups, respectively. There was no difference between the 2 groups in
      bacteremia, cytomegalovirus reactivation or disease, and fungal infection. The 3
      year transplant-related mortality (TRM) rates were 42% in the PBSC group and 31%
      in the BM controls (P =.7) and the survival rates were 46% and 51%, respectively.
      The probability of relapse was 25% and 31% in both groups (NS), resulting in
      disease-free survival rates of 43% in the PBSC group and 46% in the BM controls
      (NS). In the multivariate analysis, early disease, acute GVHD grade 0 to I, and
      presence of chronic GVHD were independent factors associated with a better
      disease-free survival in this study. PBSC from HLA-compatible unrelated donors
      can be used safely as an alternative to BM for stem cell transplantation.

PMID- 11535507
TI  - Early immunophenotypical evaluation of minimal residual disease in acute myeloid
      leukemia identifies different patient risk groups and may contribute to
      postinduction treatment stratification.
AB  - Early response to therapy is one of the most important prognostic factors in
      acute leukemia. It is hypothesized that early immunophenotypical evaluation may
      help identify patients at high risk for relapse from those who may remain in
      complete remission (CR). Using multiparametric flow cytometry, the level of
      minimal residual disease (MRD) was evaluated in the first bone marrow (BM) in
      morphologic CR obtained after induction treatment from 126 patients with acute
      myeloid leukemia (AML) who displayed aberrant phenotypes at diagnosis. Based on
      MRD level, 4 different risk categories were identified: 8 patients were at very
      low risk (fewer than 10(-4) cells), and none have relapsed thus far; 37 were at
      low risk (10(-4) to 10(-3) cells); and 64 were at intermediate risk (fewer than
      10(-3) to 10(-2) cells), with 3-year cumulative relapse rates of 14% and 50%,
      respectively. The remaining 17 patients were in the high-risk group (more than
      10(-2) residual aberrant cells) and had a 3-year relapse rate of 84% (P =.0001).
      MRD level not only influences relapse-free survival but also overall survival (P
      =.003). The adverse prognostic impact was also observed when M3 and non-M3
      patients with AML were separately analyzed, and was associated with adverse
      cytogenetic subtypes, 2 or more cycles to achieve CR, and high white blood cell
      counts. Multivariate analysis showed that MRD level was the most powerful
      independent prognostic factor, followed by cytogenetics and number of cycles to
      achieve CR. In conclusion, immunophenotypical investigation of MRD in the first
      BM in mCR obtained after AML induction therapy provides important information for
      risk assessment in patients with AML.

PMID- 11535508
TI  - The presence of a FLT3 internal tandem duplication in patients with acute myeloid
      leukemia (AML) adds important prognostic information to cytogenetic risk group
      and response to the first cycle of chemotherapy: analysis of 854 patients from
      the United Kingdom Medical Research Council AML 10 and 12 trials.
AB  - In acute myeloid leukemia (AML), further prognostic determinants are required in
      addition to cytogenetics to predict patients at increased risk of relapse. Recent
      studies have indicated that an internal tandem duplication (ITD) in the FLT3 gene
      may adversely affect clinical outcome. This study evaluated the impact of a
      FLT3/ITD mutation on outcome in 854 patients, mostly 60 years of age or younger,
      treated in the United Kingdom Medical Research Council (MRC) AML trials. An
      FLT3/ITD mutation was present in 27% of the patients and was associated with
      leukocytosis and a high percentage of bone marrow blast cells (P <.001 for both).
      It had a borderline association with a lower complete remission rate (P =.05) and
      a higher induction death rate (P =.04), and was associated with increased relapse
      risk (RR), adverse disease-free survival (DFS), event-free survival (EFS), and
      overall survival (OS) (P <.001 for all). In multivariate analysis, presence of a
      mutation was the most significant prognostic factor predicting RR and DFS (P
      <.0001) and was still significant for OS (P =.009) and EFS (P =.002). There was
      no evidence that the relative effect of a FLT3/ITD differed between the
      cytogenetic risk groups. More than one mutation was detected in 23% of
      FLT3/ITD(+) patients and was associated with worse OS (P =.04) and EFS (P =.07).
      Biallelic disease or partial/complete loss of wild-type alleles was present in
      10% of FLT3/ITD(+) patients. The suggestion is made that detection of a FLT3/ITD
      should be included as a routine test at diagnosis and evaluated for therapeutic
      management.

PMID- 11535509
TI  - Antiphospholipid antibodies and antiphospholipid syndrome in patients presenting
      with immune thrombocytopenic purpura: a prospective cohort study.
AB  - The pathogenetic role and the clinical importance of the presence of
      antiphospholipid antibodies (APAs) in patients with immune thrombocytopenic
      purpura (ITP) are not clear. In this study, the prevalence and clinical
      significance of APAs were investigated in patients with ITP. Eighty-two newly
      diagnosed ITP patients were prospectively studied. They were evaluated for the
      presence of lupus anticoagulant (LA) and immunoglobulin G/M anticardiolipin
      antibodies (ACAs). Thirty-one patients (37.8%) were APA positive at diagnosis. No
      statistically significant differences were found between the APA-positive and APA
      negative groups regarding gender, initial platelet counts, or response to
      methylprednisolone therapy. After 5 years of follow-up, cumulative thrombosis
      free survival of APA-positive (n = 31) and APA-negative (n = 51) ITP patients was
      39% and 97.7%, respectively. A significant difference was found between these
      groups by log-rank test (P =.0004). In addition, LA was an important risk marker
      for the development of thrombosis in ITP patients. After a median follow-up of 38
      months, 14 ITP patients (45%) who had APA positivity developed clinical features
      (thrombosis or fetal losses) of antiphospholipid syndrome (APS). There were no
      differences between the APA-positive patients with and without APS regarding the
      initial platelet counts, response to the therapy, or ACA positivity. The
      positivity rate for LA was significantly higher in those patients with ITP who
      developed APS (chi(2): P =.0036; relative risk 7.15; 95% confidence interval, 1.7
      47). In conclusion, this study indicates that a significant proportion of
      patients initially presenting with ITP and APA positivity developed APS. In
      patients with ITP, the persistent presence of APAs is an important risk factor
      for the development of APS.

PMID- 11535510
TI  - Specific von Willebrand factor-cleaving protease in thrombotic microangiopathies:
      a study of 111 cases.
AB  - Retrospective studies of patients with thrombotic microangiopathies (TMAs) have
      shown that a deficient activity of von Willebrand factor (vWF)-cleaving protease
      is involved in thrombotic thrombocytopenic purpura (TTP) but not in the hemolytic
      uremic syndrome (HUS). To further analyze the relevance of this enzymatic
      activity in TMA diagnosis, a 20-month multicenter study of vWF-cleaving protease
      activity was conducted in adult patients prospectively enrolled in the acute
      phase of TMA. Patients with sporadic (n = 85), intermittent (n = 21), or familial
      recurrent (n = 5) forms of TMA (66 manifesting as TTP and 45 as HUS) were
      included. TMA was either idiopathic (n = 42) or secondary to an identified
      clinical context (n = 69). vWF-cleaving protease activity was normal in 46 cases
      (7 TTP and 39 HUS) and decreased in 65 cases (59 TTP and 6 HUS). A protease
      inhibitor was detected in 31 cases and was observed only in patients manifesting
      TTP with a total absence of protease activity. Among the 111 patients, mean vWF
      antigen levels were increased and the multimeric distribution of vWF was very
      heterogeneous, showing either a defect of the high-molecular-weight forms (n =
      40), a normal pattern (n = 21), or the presence of unusually large multimers (n =
      50). Statistical analysis showed that vWF-protease deficiency was associated with
      the severity of thrombocytopenia (P <.01). This study emphasizes that vWF
      cleaving protease deficiency specifically concerns a subgroup of TMA
      corresponding to the TTP entity.

PMID- 11535511
TI  - Chronic myelogenous leukemia blast cell proliferation is inhibited by peptides
      that disrupt Grb2-SoS complexes.
AB  - Chronic myelogenous leukemia (CML) is commonly characterized by the presence of
      the p210(Bcr-Abl) oncoprotein. Many downstream effectors of Bcr-Abl have been
      described, including activation of the Grb2-SoS-Ras-MAP kinase (Erk) pathway. The
      precise contributions of these signal-transduction proteins in CML blast cells in
      human patients are not yet well defined. To gain further insight into the
      importance of Grb2 for CML, peptides that disrupt Grb2-SoS complexes were tested.
      These high-affinity Grb2-binding peptides (HAGBPs) can autonomously shuttle into
      cells and function by binding to the N-terminal SH3 domain of Grb2. The HAGBPs
      were analyzed for their effects on Bcr-Abl-expressing cell lines and freshly
      isolated CML blast cells from patients. They induced a dramatic decrease in the
      proliferation of CML cell lines. This was not observed with point-mutated control
      peptides with abolished Grb2SH3(N) binding. As expected, Grb2-SoS complexes were
      greatly diminished in the HAGBP-treated cells, and MAP kinase activity was
      significantly reduced as determined by an activation-specific phospho-MAPK
      antibody. Furthermore, cell fractions that are enriched for blast cells from CML
      patients with active disease were also incubated with the Grb2 blocker peptides.
      The HAGBPs led to a significant proliferation reduction of these cells in the
      majority of the isolates, but not in all patients' cells. These results show
      that, in addition to the direct targeting of Bcr-Abl, selective inhibition of
      Grb2 protein complexes may be a therapeutic option for a significant number of
      CML patients.

PMID- 11535512
TI  - Tumor necrosis factor (TNF)-mediated activation of the p55 TNF receptor
      negatively regulates maintenance of cycling reconstituting human hematopoietic
      stem cells.
AB  - Hematopoietic stem cell (HSC) fate decisions between self-renewal and commitment
      toward differentiation are tightly regulated in vivo. Recent developments in HSC
      culture and improvements of human HSC assays have facilitated studies of these
      processes in vitro. Through such studies stimulatory cytokines critically
      involved in HSC maintenance in vivo have been demonstrated to also promote HSC
      self-renewing divisions in vitro. Evidence for negative regulators of HSC self
      renewal is, however, lacking. Tumor necrosis factor (TNF), if overexpressed, has
      been implicated to mediate bone marrow suppression. However, whether and how TNF
      might affect the function of HSC with a combined myeloid and lymphoid
      reconstitution potential has not been investigated. In the present studies in
      vitro conditions recently demonstrated to promote HSC self-renewing divisions in
      vitro were used to study the effect of TNF on human HSCs capable of
      reconstituting myelopoiesis and lymphopoiesis in nonobese diabetic-severe
      combined immunodeficient (NOD-SCID) mice. Although all cord blood and adult bone
      marrow CD34(+)CD38(-) cells were capable of undergoing cell divisions in the
      presence of TNF, cycling HSCs exposed to TNF in vitro and in vivo were severely
      compromised in their ability to reconstitute NOD-SCID mice and long-term
      cultures. The negative effect of TNF was not dependent on the Fas pathway, and a
      similar effect could be observed using a mutant TNF exclusively targeting the p55
      TNF receptor. TNF did not appear to enhance apoptosis or affect cell-cycle
      distribution of cultured progenitors, but rather promoted myeloid
      differentiation. Thus, TNF might regulate HSC fate by promoting their
      differentiation rather than self-renewal.

PMID- 11535513
TI  - The zebrafish klf gene family.
AB  - The Kruppel-like factor (KLF) family of genes encodes transcriptional regulatory
      proteins that play roles in differentiation of a diverse set of cells in mammals.
      For instance, the founding member KLF1 (also known as EKLF) is required for
      normal globin production in mammals. Five new KLF genes have been isolated from
      the zebrafish, Danio rerio, and the structure of their products, their genetic
      map positions, and their expression during development of the zebrafish have been
      characterized. Three genes closely related to mammalian KLF2 and KLF4 were found,
      as was an ortholog of mammalian KLF12. A fifth gene, apparently missing from the
      genome of mammals and closely related to KLF1 and KLF2, was also identified.
      Analysis demonstrated the existence of novel conserved domains in the N-termini
      of these proteins. Developmental expression patterns suggest potential roles for
      these zebrafish genes in diverse processes, including hematopoiesis, blood vessel
      function, and fin and epidermal development. The studies imply a high degree of
      functional conservation of the zebrafish genes with their mammalian homologs.
      These findings further the understanding of the KLF genes in vertebrate
      development and indicate an ancient role in hematopoiesis for the Kruppel-like
      factor gene family.

PMID- 11535514
TI  - Heme is a potent inducer of inflammation in mice and is counteracted by heme
      oxygenase.
AB  - Various pathologic conditions, such as hemorrhage, hemolysis and cell injury, are
      characterized by the release of large amounts of heme. Recently, it was
      demonstrated that heme oxygenase (HO), the heme-degrading enzyme, and heme are
      able to modulate adhesion molecule expression in vitro. In the present study, the
      effects of heme and HO on inflammation in mice were analyzed by monitoring the
      biodistribution of radiolabeled liposomes and leukocytes in conjunction with
      immunohistochemistry. Small liposomes accumulate in inflamed tissues by diffusion
      because of locally enhanced vascular permeability, whereas leukocytes actively
      migrate into inflammatory areas through specific adhesive interactions with the
      endothelium and chemotaxis. Exposure to heme resulted in a dramatic increase in
      liposome accumulation in the pancreas, but also intestines, liver, and spleen
      exhibited significantly increased vascular permeability. Similarly, intravenously
      administered heme caused an enhanced influx of radiolabeled leukocytes into these
      organs. Immunohistochemical analysis showed differential up-regulation of the
      adhesion molecules ICAM-1, P-selectin, and fibronectin in liver and pancreas in
      heme-treated animals. Heme-induced adhesive properties were accompanied by a
      massive influx of granulocytes into these inflamed tissues, suggesting an
      important contribution to the pathogenesis of inflammatory processes. Moreover,
      inhibition of HO activity exacerbated heme-induced granulocyte infiltration. Here
      it is demonstrated for the first time that heme induces increased vascular
      permeability, adhesion molecule expression, and leukocyte recruitment in vivo,
      whereas HO antagonizes heme-induced inflammation possibly through the down
      modulation of adhesion molecules.

PMID- 11535515
TI  - Phenotype changes resulting in high-affinity binding of von Willebrand factor to
      recombinant glycoprotein Ib-IX: analysis of the platelet-type von Willebrand
      disease mutations.
AB  - To maintain hemostasis under shear conditions, there must be an interaction
      between the platelet glycoprotein (GP) Ib-IX receptor and the plasma ligand von
      Willebrand factor (vWf). In platelet-type von Willebrand disease (Pt-vWD),
      hemostasis is compromised. Two mutations in the GPIbalpha polypeptide chain have
      been identified in these patients-a glycine-233 to valine change and a methionine
      239 to valine change. For this investigation, these mutant proteins have been
      expressed in a Chinese hamster ovary cell model system. Ligand-binding studies
      were performed at various concentrations of ristocetin, and adhesion assays were
      performed under flow conditions. The Pt-vWD mutations resulted in a gain-of
      function receptor. vWf binding was increased at all concentrations of ristocetin
      examined, and adhesion on a vWf matrix was enhanced in terms of cell tethering,
      slower rolling velocity, and decreased detachment with increasing shear rate. Two
      other mutations were also introduced into the GPIbalpha chain. One mutation,
      encompassing both the Pt-vWD mutations, created an increase in the hydrophobicity
      of this region. The second mutation, involving a valine-234 to glycine change,
      decreased the hydrophobicity of this region. Both mutations also resulted in a
      gain-of-function receptor, with the double mutation producing a hyperreactive
      receptor for vWf. These data further support the hypothesis that ligand binding
      is regulated by conformational changes in the amino-terminal region of GPIbalpha,
      thereby influencing the stability of the GPIbalpha-vWf interaction.

PMID- 11535516
TI  - Platelet-associated anti-GPIIb-IIIa autoantibodies in chronic immune
      thrombocytopenic purpura recognizing epitopes close to the ligand-binding site of
      glycoprotein (GP) IIb.
AB  - Localization of epitopes for platelet-associated (PA) anti-GPIIb-IIIa
      (alpha(IIb)beta(3)) autoantibodies in chronic immune thrombocytopenic purpura
      remains elusive. Previous studies suggest that PA antibodies recognize the
      tertiary structure of intact glycoprotein (GP) IIb-IIIa. To localize their
      epitopes using antigen-capture enzyme-linked immunosorbent assay (ELISA), the
      reactivity of 34 PA anti-GPIIb-IIIa antibodies was examined with recombinant
      GPIIb-IIIa having a defect in ligand-binding sites in either GPIIb or GPIIIa, and
      no major conformational change was induced: KO variant GPIIb-IIIa was attributed
      to a 2-amino acid insertion between residues 160 and 161 in the W3 4-1 loop in
      GPIIb, and CAM variant GPIIb-IIIa was attributed to D119Y in GPIIIa. In one third
      (11 of 34) of the patients, PA antibodies showed a marked decrease (less than
      50%) in reactivity with KO compared with wild-type GPIIb-IIIa. Their reactivity
      was also impaired against GPIIbD163A-IIIa. In sharp contrast, they reacted
      normally with CAM GPIIb-IIIa. OP-G2, a ligand-mimetic monoclonal antibody,
      markedly inhibited their binding to GPIIb-IIIa in patients with impaired binding
      to KO GPIIb-IIIa, but small GPIIb-IIIa antagonists did not. In addition, a newly
      developed sensitive ELISA indicated that autoantibodies showing impaired binding
      to KO are more potent inhibitors for fibrinogen binding. The present data suggest
      that certain PA anti-GPIIb-IIIa autoantibodies recognize epitopes close to the
      ligand-binding site in GPIIb, but not in GPIIIa.

PMID- 11535517
TI  - Verotoxin-1-induced up-regulation of adhesive molecules renders microvascular
      endothelial cells thrombogenic at high shear stress.
AB  - Verotoxin-1 (VT-1)-producing Escherichia coli is the causative agent of
      postdiarrheal hemolytic uremic syndrome (D+HUS) of children, which leads to renal
      and other organ microvascular thrombosis. Why thrombi form only on arterioles and
      capillaries is not known. This study investigated whether VT-1 directly affected
      endothelial antithrombogenic properties promoting platelet deposition and
      thrombus formation on human microvascular endothelial cell line (HMEC-1) under
      high shear stress. Human umbilical vein endothelial cells (HUVECs) were used for
      comparison as a large-vessel endothelium. HMEC-1 and HUVECs were pre-exposed for
      24 hours to increasing concentrations of VT-1 (2-50 pM) and then perfused at 60
      dynes/cm(2) with heparinized human blood prelabeled with mepacrine. Results
      showed that VT-1 significantly increased platelet adhesion and thrombus formation
      on HMEC-1 in comparison with unstimulated control cells. An increase in thrombus
      formation was also observed on HUVECs exposed to VT-1, but to a remarkably lower
      extent. The greater sensitivity of HMEC-1 to the toxin in comparison with HUVECs
      was at least in part due to a higher expression of VT-1 receptor (20-fold more)
      as documented by FACS analysis. The HMEC-1 line had a comparable susceptibility
      to the thrombogenic effect of VT-1 as primary human microvascular cells of the
      same dermal origin (HDMECs). The adhesive molecules involved in VT-induced
      thrombus formation were also studied. Blocking the binding of von Willebrand
      factor to platelet glycoprotein Ib by aurintricarboxylic acid (ATA) or inhibition
      of platelet alpha(IIb)beta(3)-integrin by chimeric 7E3 Fab resulted in a
      significant reduction of VT-1-induced thrombus formation, suggesting the
      involvement of von Willebrand factor-platelet interaction at high shear stress in
      this phenomenon. Functional blockade of endothelial beta(3)-integrin subunit,
      vitronectin receptor, P-selectin, and PECAM-1 with specific antibodies was
      associated with a significant decrease of the endothelial area covered by
      thrombi. Confocal microscopy studies revealed that VT-1 increased the expression
      of vitronectin receptor and P-selectin and redistributed PECAM-1 away from the
      cell-cell border of HMEC-1, as well as of HDMECs, thus indicating that the above
      endothelial adhesion molecules are directly involved and possibly determine the
      effect of VT-1 on enhancing platelet adhesion and thrombus formation in
      microvascular endothelium. These results might help to explain why thrombi in HUS
      localize in microvessels rather than in larger ones and provide insights on the
      molecular events involved in the process of microvascular thrombosis associated
      with D+HUS.

PMID- 11535518
TI  - The natural history of chronic hepatitis C in a cohort of HIV-negative Italian
      patients with hereditary bleeding disorders.
AB  - This study looked at 102 anti-hepatitis C virus (HCV)-positive, hepatitis B virus
      (HBV)-negative, and HIV-negative patients (median age, 45.1 years; range, 15-71)
      affected by hereditary bleeding disorders who have been infected with HCV for 15
      to 34 years (median, 25.1). All these patients were infected before the mid 1980s
      because of non-virally inactivated pooled blood products. Fourteen patients
      (13.7%) were HCV-RNA negative with no signs of liver disease and were considered
      to have cleared the virus. Eighty-eight patients (86.3%) were HCV-RNA positive.
      The HCV genotype distribution was 1a in 20.5%, 1b in 36.4%, 2 in 17.0%, 3 in
      15.9%, 4 in 3.4%, and mixed in 6.8% of cases. Twenty-four patients (23.5%) had
      serum cryoglobulins, symptomatic in 4 cases, and associated with liver disease
      and with genotype 1. Among the 88 HCV-RNA-positive patients, 15 (17.0%) had
      normal alanine aminotransferase levels and abdominal ultrasound, 61 (69.3%) had
      nonprogressive chronic hepatitis, and 12 (13.7%) had severe liver disease (6
      [6.9%] liver cirrhosis, 4 [4.5%] hepatic decompensation, and 2 [2.3%]
      hepatocellular carcinoma) after a follow-up period of 25 years. There were 3
      (3.4%) liver-related deaths. HCV genotype 1, patient's age at evaluation,
      duration of infection, and severity of congenital bleeding disorder were
      associated with more advanced liver disease. The results confirm the slow
      progression of HCV infection in HIV-negative hemophiliacs.

PMID- 11535519
TI  - Decreased von Willebrand factor protease activity associated with
      thrombocytopenic disorders.
AB  - Recent studies investigating thrombotic thrombocytopenic purpura (TTP) have
      implicated abnormal plasma von Willebrand factor (vWF)-cleaving metalloprotease
      activity in this disorder. It has been proposed that a metalloprotease cleaves
      unusually large (UL) multimers of vWF, which enter the circulation from the
      endothelium. Abnormal metalloprotease activity could result in ULvWF, which could
      participate in TTP. However, the diagnostic specificity of abnormalities in the
      plasma metalloprotease activity has not been established. A prospective study of
      vWF protease activity was performed using samples from 20 healthy controls, 20
      patients with acute TTP, 20 patients with immune idiopathic thrombocytopenic
      purpura (ITP), 10 patients with disseminated intravascular thrombocytopenia
      (DIC), 10 patients with systemic lupus erythematosus (SLE,) and 5
      thrombocytopenic patients with leukemia. Studies were performed blinded to the
      diagnosis. Samples from hospitalized patients with normal platelet counts were
      also tested. The vWF digests and multimer analysis were done using previously
      described methods. Six laboratory personnel independently scored each of the
      multimer gels. Reduced protease activity was observed in 9 of 20 patients with
      TTP. Reduced activity was also observed in 6 of 20 patients with ITP, 6 of 10
      patients with DIC, 5 of 10 patients with SLE, 1 of 5 patients with leukemia, 2 of
      20 healthy controls, and 3 of 25 hospitalized patients. This study indicates that
      abnormalities of vWF protease activity are not restricted to patients with the
      diagnosis of TTP.

PMID- 11535520
TI  - Transplacentally acquired maternal T lymphocytes in severe combined
      immunodeficiency: a study of 121 patients.
AB  - A study in 121 infants with severe combined immunodeficiency (SCID) was performed
      to determine the prevalence of an engraftment by transplacentally acquired
      maternal T cells and to explore clinical and immunological findings related to
      this abnormality. Each newly diagnosed patient with SCID presenting with
      circulating T cells was evaluated for chimerism by performing selective HLA
      typing of T cells and non-T cells. In patients with engraftment, maternal T cells
      were characterized phenotypically and functionally, and results were correlated
      with clinical findings in the patients. Maternal T cells were detected in the
      circulation in 48 patients; these cells ranged from fewer than 100/microL in 14
      cases to more than 2000/microL in 4 cases (median, 415/microL). Clinical signs of
      graft-versus-host disease (GVHD) were absent in 29 patients. In the other cases,
      manifestations of GVHD were present, involving the skin and in 14 cases also the
      liver. Skin GVHD was mild in 8 patients. In these patients, as well as in
      patients with no signs of GVHD, maternal T cells were predominantly CD8(+) and,
      with one exception, failed to respond to mitogen stimulation. In 9 patients,
      manifestations of skin GVHD were prominent. T cells in these cases were
      predominantly CD4(+) and responded, with one exception, to mitogen stimulation.
      In 8 of the cases with prominent skin GVHD, the underlying SCID variant was
      characterized by the absence of B cells. In this study, further understanding is
      provided of a phenomenon that is responsible for the significant heterogeneity of
      clinical and immunological findings in SCID.

PMID- 11535521
TI  - Immunotherapy using heat-shock protein preparations of leukemia cells after
      syngeneic bone marrow transplantation in mice.
AB  - Heat-shock proteins (HSPs) act as molecular chaperones binding endogenous
      antigenic peptides and transporting them to major histocompatibility complexes.
      HSPs chaperone a broad repertoire of endogenous peptides including tumor
      antigens. For the immunotherapy of tumors, a strategy using HSPs may be more
      advantageous than other procedures because the identification of each tumor
      specific antigen is not necessary. In this study, the efficacy of immunotherapy
      against minimal residual leukemia cells using HSP preparations was evaluated.
      HSP70 and GP96 were purified from syngeneic leukemia cell line A20 and immunized
      into BALB/c mice during the reconstitution period of the immune system after
      syngeneic bone marrow transplantation. In this procedure, all mice not immunized
      were dead within 60 days of A20 inoculation, whereas the survival times of HSP
      immunized mice were significantly prolonged. In addition, the depletion of either
      CD4(+) or CD8(+) T lymphocyte significantly abrogated this efficacy, indicating
      that both CD4(+) and CD8(+) T lymphocytes were required for tumor cell rejection.
      Moreover, the vaccination of HSPs elicited a specific response of potent CD8(+) T
      lymphocytes cytotoxic against A20 in vitro. These observations suggest that
      immunization of the complex of HSPs and peptides derived from leukemia cells
      leads to immune responses. These immune responses are sufficient to reject
      minimal amounts of leukemia cells for relatively immunocompromised mice after
      syngeneic bone marrow transplantation.

PMID- 11535522
TI  - CD8(+) T cells are an in vivo reservoir for human T-cell lymphotropic virus type
      I.
AB  - It is thought that human T-cell lymphotropic virus type I (HTLV-I) preferentially
      infects CD4(+) T cells in vivo. However, observations of high HTLV-I proviral
      load in patients with HTLV-I-associated myelopathy/tropical spastic paraparesis
      suggest that HTLV-I may infect other cell types in addition to CD4(+) T cells. To
      identify in vivo T-cell tropisms of HTLV-I, real-time quantitative polymerase
      chain reaction (PCR) and intracellular protein staining were used. A high amount
      of HTLV-I proviral DNA was detected from purified CD8(+) T cells by quantitative
      PCR (between 1.64 and 62.83 copies of HTLV-I provirus per 100 isolated CD8(+) T
      cells). CD8(+) T cells expressed HTLV-I-related antigens (HTLV-I Tax and p19
      protein) after a short time in cultivation. These results demonstrate that CD8(+)
      T cells are also infected with HTLV-I and express HTLV-I antigens at levels that
      are comparable to HTLV-I-infected CD4(+) cells. Therefore, CD8(+) cells are an
      additional viral reservoir in vivo for HTLV-I and may contribute to the
      pathogenesis of HTLV-I-mediated disorders.

PMID- 11535523
TI  - Long-lived polyclonal B-cell lines derived from midgestation mouse embryo
      lymphohematopoietic progenitors reconstitute adult immunodeficient mice.
AB  - Lymphohematopoietic progenitors derived from midgestation mouse embryos were
      established in long-term cultures with stromal cell monolayers and interleukin 7
      (IL-7), giving rise to B-lineage cell lines. The initial emergence and in vitro
      establishment of these early embryo cell lines were highly sensitive to IL-7
      mediated signals, in comparison to cell lines similarly obtained using precursors
      from late fetal liver (> 13 days postcoitum) and adult bone marrow. The early
      embryo-derived progenitors spontaneously differentiated in vitro to CD19(+)IgM(+)
      immature B cells in the presence of optimal concentrations of IL-7, in contrast
      to those progenitors obtained from late gestation and adult mice, whose
      differentiation only occurred in the absence of IL-7. The newly in vitro
      generated B cells of the early embryo cell lines repopulated adult
      immunodeficient severe combined immunodeficient mice on their adoptive transfer
      in vivo and generated specific humoral immune responses after immunization.

PMID- 11535524
TI  - Efficient identification of HLA-A*2402-restricted cytomegalovirus-specific CD8(+)
      T-cell epitopes by a computer algorithm and an enzyme-linked immunospot assay.
AB  - Antigenic peptides recognized by virus-specific cytotoxic T lymphocytes (CTLs)
      are useful tools for studying the CTL responses exclusively among those who own
      the major histocompatibility complex (MHC) class I molecules that present the
      peptides. For widening the application, an efficient strategy to determine such
      epitopes in the context of a given MHC is highly desirable. A rapid and efficient
      strategy is presented for the determination of CTL epitopes in the context of
      given MHC molecules of interest through multiple screenings consisting of a
      computer-assisted algorithm and MHC stabilization and enzyme-linked immunospot
      assays. A major cytomegalovirus (CMV)-specific CTL epitope, QYDPVAALF, in the
      amino acid sequence of its lower matrix 65 kd phosphoprotein (pp65) presented by
      HLA-A*2402 molecules was identified from 83 candidate peptides. The results
      indicate that the CMV-specific CTL response is highly focused to pp65 in the
      context of HLA-A*2402. Endogenous processing and presentation was confirmed using
      a peptide-specific CD8(+) T-cell clone as the effectors and autologous fibroblast
      cells infected with recombinant vaccinia virus expressing pp65 gene or CMV as
      antigen-presenting cells. Flow cytometric analysis of intracellular interferon
      gamma production revealed 0.04% to 0.27% of CD8(+) T cells in peripheral blood of
      HLA-A24(+) and CMV-seropositive donors to be specific for the peptide. The
      tetrameric MHC-peptide complexes specifically bound to the reactive T-cell clone
      and 0.79% of CD8(+) T cells in peripheral blood from a seropositive donor. The
      peptide could be a useful reagent to study CTL responses to CMV among populations
      positive for HLA-A*2402.

PMID- 11535525
TI  - Differential cellular targets of Epstein-Barr virus (EBV) infection between acute
      EBV-associated hemophagocytic lymphohistiocytosis and chronic active EBV
      infection.
AB  - Unusual Epstein-Barr virus (EBV) infection into T or natural killer cells plays a
      pivotal role in the pathogenesis of acute EBV-associated hemophagocytic
      lymphohistiocytosis (EBV-HLH) and chronic active EBV infection (CAEBV). The
      precise frequency and localization of EBV genome in lymphocyte subpopulations
      especially within T-cell subpopulations are unclear in these EBV-related
      disorders. This study analyzed the frequency of EBV-infected cells in circulating
      lymphocyte subpopulations from 4 patients with acute EBV-HLH and 4 with CAEBV.
      EBV- encoded small RNA-1 in situ hybridization examination of peripheral blood
      lymphocytes showed a significantly higher frequency of EBV-infected cells of 1.0%
      to 13.4% in EBV-HLH and 1.6% to 25.6% in CAEBV, respectively. The patterns of EBV
      infection in lymphocyte subpopulations were quite different between acute EBV-HLH
      and CAEBV. EBV infection was predominant in CD8(+) T cells in all EBV-HLH
      patients, whereas the dominant EBV-infected cell populations were non-CD8(+)
      lymphocyte subpopulations in CAEBV patients. Phenotypical analysis revealed that
      EBV-infected cell populations from both EBV-HLH and CAEBV were activated. There
      was no predominance of any EBV substrain of latent membrane protein-1, EBV
      associated nuclear antigen (EBNA)-1, and EBNA-2 genes between the 2 abnormal EBV
      associated disorders, and self-limited acute infectious mononucleosis. These
      results showing differential virus-cell interactions between acute EBV-HLH and
      CAEBV indicated different pathogenic mechanisms against EBV infection between the
      2 EBV-associated diseases, which accounts for the difference in clinical
      manifestations between the 2 diseases.

PMID- 11535526
TI  - Autoreactive CD4(+) T-cell clones to beta2-glycoprotein I in patients with
      antiphospholipid syndrome: preferential recognition of the major phospholipid
      binding site.
AB  - Autoreactive CD4(+) T cells to beta2-glycoprotein I (beta2GPI) that promote
      antiphospholipid antibody production were recently identified in patients with
      antiphospholipid syndrome (APS). To further examine antigen recognition profiles
      and T-cell helper activity in beta2GPI-reactive T cells, 14 CD4(+) T-cell clones
      specific to beta2GPI were generated from 3 patients with APS by repeated
      stimulation of peripheral blood T cells with recombinant beta2GPI. At least 4
      distinct T-cell epitopes were identified, but the majority of the beta2GPI
      specific T-cell clones responded to a peptide encompassing amino acid residues
      276 to 290 of beta2GPI (KVSFFCKNKEKKCSY; single-letter amino acid codes) that
      contains the major phospholipid-binding site in the context of the DRB4*0103
      allele. Ten of 12 beta2GPI-specific T-cell clones were able to stimulate
      autologous peripheral blood B cells to promote anti-beta2GPI antibody production
      in the presence of recombinant beta2GPI. T-cell helper activity was exclusively
      found in T-cell clones capable of producing interleukin 6 (IL-6). In vitro anti
      beta2GPI antibody production induced by T-cell clones was inhibited by anti-IL-6
      or anti-CD40 ligand monoclonal antibody. In addition, exogenous IL-6 augmented
      anti-beta2GPI antibody production in cultures of the T-cell clone lacking IL-6
      expression. These results indicate that beta2GPI-specific CD4(+) T cells in
      patients with APS preferentially recognize the antigenic peptide containing the
      major phospholipid-binding site and have the capacity to stimulate B cells to
      produce anti-beta2GPI antibodies through IL-6 expression and CD40-CD40 ligand
      engagement. These findings are potentially useful for clarifying the pathogenesis
      of APS and for developing therapeutic strategies that suppress pathogenic
      antiphospholipid antibody production in these patients.

PMID- 11535527
TI  - Reduction in drug-induced DNA double-strand breaks associated with beta1 integrin
      mediated adhesion correlates with drug resistance in U937 cells.
AB  - We previously showed that adhesion of myeloma cells to fibronectin (FN) by means
      of beta1 integrins causes resistance to certain cytotoxic drugs. The study
      described here found that adhesion of U937 human histiocytic lymphoma cells to FN
      provides a survival advantage with respect to damage induced by the topoisomerase
      (topo) II inhibitors mitoxantrone, doxorubicin, and etoposide. Apoptosis induced
      by a topo II inhibitor is thought to be initiated by DNA damage. The neutral
      comet assay was used to determine whether initial drug-induced DNA damage
      correlated with cellular-adhesion-mediated drug resistance. Cellular adhesion by
      means of beta1 integrins resulted in a 40% to 60% reduction in mitoxantrone- and
      etoposide-induced DNA double-strand breaks. When the mechanisms regulating the
      initial drug-induced DNA damage were examined, a beta1 integrin-mediated
      reduction in drug-induced DNA double-strand breaks was found to correlate with
      reduced topo II activity and decreased salt-extractable nuclear topo IIbeta
      protein levels. Confocal studies showed changes in the nuclear localization of
      topo IIbeta; however, alterations in the nuclear-to-cytoplasmic ratio of topo
      IIbeta in FN-adhered cells were not significantly different. Furthermore, after a
      high level of salt extraction of nuclear proteins, higher levels of topo IIbeta
      associated DNA binding were observed in FN-adhered cells than in cells in
      suspension. Together, these data suggest that topo IIbeta is more tightly bound
      to the nucleus of FN-adhered cells. Thus, FN adhesion by means of beta1 integrins
      appears to protect U937 cells from initial drug-induced DNA damage by reducing
      topo II activity secondarily to alterations in the nuclear distribution of topo
      IIbeta.

PMID- 11535528
TI  - Vascular endothelial growth factor (VEGF) is an autocrine growth factor for VEGF
      receptor-positive human tumors.
AB  - Angiogenesis is required for the progression of tumors from a benign to a
      malignant phenotype and for metastasis. Malignant tumor cells secrete factors
      such as vascular endothelial growth factor (VEGF), which bind to their cognate
      receptors on endothelial cells to induce angiogenesis. Here it is shown that
      several tumor types express VEGF receptors (VEGFRs) and that inhibition of VEGF
      (VEGF antisense oligonucleotide AS-3) or VEGFRs (neutralizing antibodies)
      inhibited the proliferation of these cell lines in vitro. Furthermore, this
      effect was abrogated by exogenous VEGF. Thus, VEGF is an autocrine growth factor
      for tumor cell lines that express VEGFRs. A modified form of VEGF AS-3 (AS-3m),
      in which flanking 4 nucleotides were substituted with 2-O-methylnucleosides
      (mixed backbone oligonucleotides), retained specificity and was active when given
      orally or systemically in vitro and in murine tumor models. In VEGFR-2-expressing
      tumors, VEGF inhibition may have dual functions: direct inhibition of tumor cell
      growth and inhibition of angiogenesis.

PMID- 11535529
TI  - Transcription patterning of uncoupled proliferation and differentiation in
      myelodysplastic bone marrow with erythroid-focused arrays.
AB  - Because abnormal erythroid differentiation is the most common manifestation of
      the myelodysplastic syndromes (MDS), it was hypothesized that erythroid gene
      expression may be used to illustrate myelodysplastic transcription patterns. Ten
      normal bone marrow aspirates (NBM) were first analyzed using an erythroid-focused
      cDNA array to define steady-state transcription levels. Proliferation and
      differentiation gene subsets were identified by statistically significant
      differences between NBM and erythroleukemia gene expression. Next, cDNAs from 5
      separate MDS aspirates were studied: refractory anemia, refractory anemia with
      ringed sideroblasts, refractory anemia with excess blasts, refractory anemia with
      excess blasts in transformation (RAEB-T), and RAEB-T/secondary MDS. A distinct
      pattern of significantly increased proliferation-associated and reduced
      differentiation-associated gene activity was established for MDS.

PMID- 11535530
TI  - Expression of high Km 5'-nucleotidase in leukemic blasts is an independent
      prognostic factor in adults with acute myeloid leukemia.
AB  - Cytarabine (ara-C) requires activation into its triphosphorylated form, ara-CTP,
      to exert cytotoxic activity. Cytoplasmic 5'-nucleotidase (5NT) dephosphorylates
      ara-CMP, a key intermediate, preventing accumulation of ara-CTP and may reduce
      cellular sensitivity to the cytotoxic activity of ara-C. To determine whether the
      level of expression of 5NT is correlated with clinical outcome in patients with
      acute myeloid leukemia (AML) treated with ara-C, this study analyzed the levels
      of messenger RNA expression of high Km 5NT by real-time polymerase chain reaction
      at diagnosis in blast cells of 108 patients with AML. High Km 5NT was expressed
      at diagnosis in the blast cells of 54% of patients. In univariate analysis, (1)
      patients whose blast cells contained high levels (values greater than the median
      value for total population) of high Km 5NT at diagnosis had significantly shorter
      disease-free survival (DFS) than patients with low levels of high Km 5NT (11
      months versus 17.5 months, P =.02) and (2) high levels of high Km 5NT also
      predicted significantly shorter overall survival (15.7 months versus 39 months, P
      = .01) in young patients (< or = 57 years; median value for the entire
      population). In a multivariate analysis taking into account age, karyotype risk,
      and other factors found to have prognostic significance in univariate analysis,
      (1) high Km 5NT expression was an independent prognostic factor for DFS and (2)
      high levels of high Km 5NT also predicted significantly shorter overall survival
      in young patients. These results demonstrate that the expression of high levels
      of high Km 5NT in blast cells is correlated with outcome in patients with AML.

PMID- 11535531
TI  - Enhanced ceramide generation and induction of apoptosis in human leukemia cells
      exposed to DT(388)-granulocyte-macrophage colony-stimulating factor (GM-CSF), a
      truncated diphtheria toxin fused to human GM-CSF.
AB  - DT(388)-GM-CSF, a targeted fusion toxin constructed by conjugation of human
      granulocyte-macrophage colony-stimulating factor (GM-CSF) with the catalytic and
      translocation domains of diphtheria toxin, is presently in phase I trials for
      patients with resistant acute myeloid leukemia. HL-60/VCR, a multidrug-resistant
      human myeloid leukemia cell line, and wild-type HL-60 cells were used to study
      the impact of DT(388)-GM-CSF on metabolism of ceramide, a modulator of apoptosis.
      After 48 hours with DT(388)-GM-CSF (10 nM), ceramide levels in HL-60/VCR cells
      rose 6-fold and viability fell to 10%, whereas GM-CSF alone was without
      influence. Similar results were obtained in HL-60 cells. Examination of the time
      course revealed that protein synthesis decreased by about 50% and cellular
      ceramide levels increased by about 80% between 4 and 6 hours after addition of
      DT(388)-GM-CSF. By 6 hours this was accompanied by activation of caspase-9,
      followed by activation of caspase-3, cleavage of caspase substrates, and
      chromatin fragmentation. Hygromycin B and emetine failed to elevate ceramide
      levels or induce apoptosis at concentrations that inhibited protein synthesis by
      50%. Exposure to C(6)-ceramide inhibited protein synthesis (EC(50) approximately
      5 microM) and decreased viability (EC(50) approximately 6 microM).
      Sphingomyelinase treatment depleted sphingomyelin by about 10%, while increasing
      ceramide levels and inhibiting protein synthesis. Diphtheria toxin increased
      ceramide and decreased sphingomyelin in U-937 cells, a cell line extremely
      sensitive to diphtheria toxin; exposure to DT(388)-GM-CSF showed sensitivity at
      less than 1.0 pM. Diphtheria toxin and conjugate trigger ceramide formation that
      contributes to apoptosis in human leukemia cells through caspase activation and
      inhibition of protein synthesis.

PMID- 11535532
TI  - The deubiquitinating enzyme DUB-2 prolongs cytokine-induced signal transducers
      and activators of transcription activation and suppresses apoptosis following
      cytokine withdrawal.
AB  - Cytokines, such as interleukin-2 (IL-2), activate intracellular signaling
      pathways via rapid tyrosine phosphorylation of their receptors, resulting in the
      activation of many genes involved in cell growth and survival. The
      deubiquitinating enzyme DUB-2 is induced in response to IL-2 but as yet its
      function has not been determined. The results of this study show that DUB-2 is
      expressed in human T-cell lymphotropic virus-I (HTLV-1)-transformed T cells that
      exhibit constitutive activation of the IL-2 JAK/STAT (signal transducers and
      activators of transcription) pathway, and when expressed in Ba/F3 cells DUB-2
      markedly prolonged IL-2-induced STAT5 phosphorylation. Although DUB-2 did not
      enhance IL-2-mediated proliferation, when withdrawn from growth factor, cells
      expressing DUB-2 had sustained STAT5 phosphorylation and enhanced expression of
      IL-2-induced genes cis and c-myc. Moreover, DUB-2 expression markedly inhibited
      apoptosis induced by cytokine withdrawal allowing cells to survive. Taken
      together these data suggest that DUB-2 can enhance signaling through the JAK/STAT
      pathway, prolong lymphocyte survival, and, when constitutively expressed, may
      contribute to the activation of the JAK/STAT pathway observed in some transformed
      cells.

PMID- 11535533
TI  - Prostaglandin D2 is a potent chemoattractant for human eosinophils that acts via
      a novel DP receptor.
AB  - Prostaglandin D2 (PGD2) is released following exposure of asthmatics to allergen
      and acts via the adenylyl cyclase-coupled receptor for PGD2 (DP receptor). In
      this study, it is reported that human eosinophils possess this receptor, which
      would be expected to inhibit their activation. In contrast, it was found that
      prostaglandin D2 is a potent stimulator of eosinophil chemotaxis, actin
      polymerization, CD11b expression, and L-selectin shedding. These responses are
      specific for eosinophils, as neutrophils display little or no response to
      prostaglandin D2. They were not due to interaction with receptors for other
      prostanoids, as prostaglandins E2 and F(2alpha), U46619 (a thromboxane A2
      analogue), and carbaprostacyclin (a prostacyclin analogue) displayed little or no
      activity. Furthermore, they were not shared by the selective DP receptor agonist
      BW245C and were not prevented by the selective DP receptor antagonist BWA868C,
      indicating that they were not mediated by DP receptors. In contrast, the
      prostaglandin D2 metabolite 13,14-dihydro-15-oxoprostaglandin D2 induced
      eosinophil activation but did not stimulate DP receptor-mediated adenosine 3',5'
      cyclic monophosphate (cAMP) formation. These results indicate that in addition to
      the classic inhibitory DP1 receptor, eosinophils possess a second, novel DP2
      receptor that is associated with PGD2-induced cell activation. These 2 receptors
      appear to interact to regulate eosinophil responses to PGD2, as blockade of DP1
      receptor-mediated cAMP production by BWA868C resulted in enhanced DP2 receptor
      mediated stimulation of CD11b expression. The balance between DP1 and DP2
      receptors could determine the degree to which prostaglandin D2 can activate
      eosinophils and may play a role in eosinophil recruitment in asthma.

PMID- 11535534
TI  - Regulation of expression of murine transferrin receptor 2.
AB  - Complementary and genomic DNA for the murine transferrin receptor 2 (TfR2) were
      cloned and mapped to chromosome 5. Northern blot analysis showed that high levels
      of expression of murine TfR2 occurred in the liver, whereas expression of TfR1 in
      the liver was relatively low. During liver development, TfR2 was up-regulated and
      TfR1 was down-regulated. During erythrocytic differentiation of murine
      erythroleukemia (MEL) cells induced by dimethylsulfoxide, expression of TfR1
      increased, whereas TfR2 decreased. In MEL cells, expression of TfR1 was induced
      by desferrioxamine, an iron chelator, and it was reduced by ferric nitrate. In
      contrast, levels of TfR2 were not affected by the cellular iron status. Reporter
      assay showed that GATA-1, an erythroid-specific transcription factor essential
      for erythrocytic differentiation at relatively early stages, enhanced TfR2
      promoter activity. Interestingly, FOG-1, a cofactor of GATA-1 required for
      erythrocyte maturation, repressed the enhancement of the activity by GATA-1.
      Also, CCAAT-enhancer binding protein, which is abundant in liver, enhanced the
      promoter activity. Thus, tissue distribution of TfR2 was consistent with the
      reporter assays. Expression profiles of TfR2 were different from those of TfR1,
      suggesting unique functions for TfR2, which may be involved in iron metabolism,
      hepatocyte function, and erythrocytic differentiation.

PMID- 11535535
TI  - P-selectin mediates the adhesion of sickle erythrocytes to the endothelium.
AB  - The adherence of sickle red blood cells (RBCs) to the vascular endothelium may
      contribute to painful vaso-occlusion in sickle cell disease. Sickle cell
      adherence involves several receptor-mediated processes and may be potentiated by
      the up-regulated expression of adhesion molecules on activated endothelial cells.
      Recent results showed that thrombin rapidly increases the adhesivity of
      endothelial cells for sickle erythrocytes. The current report presents the first
      evidence for the novel adhesion of normal and, to a greater extent, sickle RBCs
      to endothelial P-selectin. Studies of the possible interaction of erythrocytes
      with P-selectin revealed that either P-selectin blocking monoclonal antibodies or
      sialyl Lewis tetrasaccharide inhibits the enhanced adherence of normal and sickle
      cells to thrombin-treated endothelial cells. Both RBC types also adhere to
      immobilized recombinant P-selectin. Pretreating erythrocytes with sialidase
      reduces their adherence to activated endothelial cells and to immobilized
      recombinant P-selectin. Herein the first evidence is presented for the binding of
      normal or sickle erythrocytes to P-selectin. This novel finding suggests that P
      selectin inhibition be considered as a potential approach to therapy for the
      treatment of painful vaso-occlusion in sickle cell disease.

PMID- 11535536
TI  - Decreased immune functions of blood cells following mobilization with granulocyte
      colony-stimulating factor: association with donor characteristics.
AB  - In this study, mononuclear cells (MNCs) from granulocyte colony-stimulating
      factor (G-CSF)-mobilized blood stem cell (BSC) harvests from 104 healthy donors
      were analyzed for their immunological functions and compared with MNCs from 28
      steady-state nonmobilized donors. The relationships between donor characteristics
      (age, gender, weight, and HLA type) and immune functions of the harvests were
      also analyzed. There was a significant (P <.01) decrease in natural killer and
      lymphokine-activated killer (LAK) cell-mediated cytotoxicity for G-CSF-mobilized
      effector cells compared with nonmobilized cells. Similarly, there was a
      significant (P <.005) decrease in both T-cell and B-cell mitogen response in G
      CSF-mobilized cells compared with nonmobilized cells. There was dose-dependent
      inhibition of LAK cell-mediated cytotoxicity, but this effect was not seen with
      other immune function assays. Changes in immune function did not appear to be
      determined by frequency of cellular phenotypes or expression of effector function
      genes seen in a reverse-transcription polymerase chain reaction. There was a
      significant relationship between expression of certain HLA alleles (A1, A3, A24,
      B44, B62, DR15, DR17; all P <.01) and increased immune function, such as
      cytotoxicity and/or mitogen response. A decrease in immune function with the HLA
      DR13 expression was also observed (P <.01). Since the G-CSF increases the number
      of MNCs, the increase in effector cells might compensate for decreased immune
      functions of these cells in vivo when transplanted into patients. These results
      suggest a decreased immune function in G-CSF-mobilized BSC harvests and warrant
      further studies to correlate these data with clinical outcome.

PMID- 11535537
TI  - Quantification of polyoma BK viruria in hemorrhagic cystitis complicating bone
      marrow transplantation.
AB  - Polyoma BK virus (BKV) is frequently identified in the urine of bone marrow
      transplantation (BMT) patients with hemorrhagic cystitis (HC). However, viruria
      is common even in asymptomatic patients, making a direct causative role of BKV
      difficult to establish. This study prospectively quantified BK viruria and
      viremia in 50 BMT patients to define the quantitative relationship of BKV
      reactivation with HC. Adenovirus (ADV) was similarly quantified as a control.
      More than 800 patient samples were quantified for BKV VP1 gene with a real-time
      quantitative polymerase chain reaction. Twenty patients (40%) developed HC, 6
      with gross hematuria (HC grade 2 or higher) and 14 with microscopic hematuria (HC
      grade 1). When compared with asymptomatic patients, patients with HC had
      significantly higher peak BK viruria (6 x 10(12) versus 5.7 x 10(7) genome
      copies/d, P <.001) and larger total amounts of BKV excreted during BMT (4.9 x
      10(13) versus 7.7 x 10(8) genome copies, P <.001). There was no detectable
      increase in BK viremia. Binary logistic regression analysis showed that BK
      viruria was the only risk factor, with HC not related to age, conditioning
      regimen, type of BMT, and graft-versus-host disease. Furthermore, the levels of
      ADV viruria in patients with or without HC were similar and comparable with those
      of BK viruria in patients without HC, suggesting that the significant increase in
      BK viruria in HC patients was not due to background viral reactivation or damage
      to the urothelium. BK viruria was quantitatively related to the occurrence of HC
      after BMT.

PMID- 11535538
TI  - Solid tumors after chronic lymphocytic leukemia.
AB  - Prior reports indicate that patients with chronic lymphocytic leukemia (CLL) may
      be at increased risk of subsequent neoplasms. This study quantified the risk of
      second cancers among 16 367 patients with CLL in the population-based
      Surveillance, Epidemiology and End Results Program. Overall, the
      observed/expected ratio (O/E) was 1.20 (95% confidence interval [CI], 1.15-1.26).
      Second cancer risks for patients who received chemotherapy only as the first
      course of treatment (O/E = 1.21) were similar to risks for those who received no
      treatment initially (O/E = 1.19). Significant excesses were found for Kaposi
      sarcoma (O/E = 5.09), malignant melanoma (O/E = 3.18), and cancers of the larynx
      (O/E = 1.72) and the lung (O/E = 1.66). Increased risks were also found for brain
      cancer among men (O/E =1.91) and for cancers of the stomach (O/E = 1.76) and
      bladder (O/E = 1.52) among women. Additional investigations of cancers after CLL
      are needed to explore the role of immunologic impairment and/or other etiologic
      influences.

PMID- 11535539
TI  - The significance of graft-versus-host disease and pretransplantation minimal
      residual disease status to outcome after allogeneic stem cell transplantation in
      patients with acute lymphoblastic leukemia.
AB  - Relapse is the major cause of treatment failure after allogeneic stem cell
      transplantation (SCT) in patients with acute lymphoblastic leukemia. Minimal
      residual disease (MRD) was analyzed before SCT in 30 patients with acute
      lymphoblastic leukemia. The aim was to determine whether the level of MRD before
      transplantation was correlated with outcome. Fifteen patients were found to have
      high-level MRD (10(-2) to 10(-3)), 10 had low-level MRD (< 10(-3)), and 5 were
      MRD(-). Among MRD(-) patients the probability of relapse was 0 in 5, which was
      less than in MRD(+) patients (13 of 25) (P =.05). No major difference was found
      between the high- and low-level MRD(+) groups. Among the MRD(+) patients, only 2
      of 11 with acute and chronic graft-versus-host disease had a relapse, versus 11
      of 14 without (P =.005). In conclusion, for patients entering transplantation
      while they have residual disease, a combination of acute and chronic graft-versus
      host disease may be needed to decrease the risk of relapse after SCT.

PMID- 11535540
TI  - Myelodysplastic syndromes standardized response criteria: further definition.

PMID- 11535541
TI  - Microsatellite instability in sporadic colon cancer is associated with an
      improved prognosis at the population level.
AB  - Some previous studies have reported an improved prognosis in sporadic colon
      cancers with microsatellite instability, whereas others have not. In addition,
      relatively few of those reporting an improved prognosis controlled for tumor
      stage or were population-based. Therefore, we evaluated the relationship between
      microsatellite instability and prognosis, tumor stage, and other clinical
      variables in a population-based study of 1026 individuals. Microsatellite
      instability was determined by the noncoding mononucleotide repeat BAT-26 and the
      coding mononucleotide repeat in transforming growth factor-beta receptor type II.
      Significant relationships were seen between microsatellite instability and
      proximal tumor location, female gender, young and old age at diagnosis, poor
      histological differentiation, and low tumor stage (P < 0.01). There was a
      significant relationship between microsatellite instability and improved
      prognosis, even after adjusting for stage, with a reduction in the risk of death
      attributable to colon cancer of approximately 60%. Most of this risk reduction
      occurred in individuals with American Joint Committee on Cancer stage III tumors,
      although transforming growth factor-beta receptor type II mutations were
      associated with a significant reduction in colon cancer death in tumors with
      distant metastases. We conclude that microsatellite instability in sporadic colon
      cancer is associated with an improved prognosis at the population level.

PMID- 11535542
TI  - Evaluation of epithelial cell proliferation rate in normal-appearing colonic
      mucosa as a high-risk marker for colorectal cancer.
AB  - To determine whether the colonic epithelial proliferation rate is useful as a
      marker for colorectal cancer, we measured the Ki-67 labeling index (LI) in normal
      appearing mucosa from the sigmoid and ascending colon in patients with two or
      more tumors (early cancers, which are defined as tumors the depth of invasion of
      which is limited to mucosal layer or submucosal layer, adenomas, or both). The
      association of baseline LI with the risk of development of colon tumors 2 years
      after endoscopic removal was assessed by cohort analysis. The presence of two or
      more tumors was defined as occurrence. One hundred and six specimens from the
      sigmoid colon and 130 from the ascending colon from 246 subjects (203 males and
      43 females) were used for analysis. The patients with higher upper-third LI in
      the normal-appearing mucosa in the sigmoid colon, but not in the ascending colon,
      had significantly more tumors at follow-up colonoscopy 2 years later (risk ratio,
      3.6; 95% confidence interval, 1.2-10.6). Moreover, multivariate analysis showed
      that it was an independent factor. We concluded that the higher upper-third Ki-67
      LI of normal-appearing mucosa in the sigmoid colon indicates a high risk for
      colorectal cancer.

PMID- 11535543
TI  - An association between genetic polymorphisms in the ileal sodium-dependent bile
      acid transporter gene and the risk of colorectal adenomas.
AB  - Epidemiological and experimental studies have implicated bile acids (particularly
      secondary bile acids) as important factors in the development of colorectal
      cancer. The ileal sodium-dependent bile acid transporter (ISBT) is a crucial
      player in the enterohepatic circulation of bile acids. Genetic defects in ISBT
      may result in malabsorption of bile acids and a loss of bile acids into the large
      intestine, with a resultant increase in the cytotoxic secondary bile acids in the
      colon. In a case-control study, we investigated the association between two
      sequence variations in SLC10A2, the gene encoding ISBT, and colorectal adenomas,
      a precursor lesion of colorectal cancer. The frequency of the missense mutation
      in codon 171 of exon 3 (a nucleotide transversion from G to T resulting in an
      alanine to serine substitution) was not significantly different between cases and
      controls. However, we found a 2-fold higher risk of colorectal adenomas
      associated with a C-->T nucleotide transition in codon 169 of exon 3 (odds ratio
      = 2.06; 95% confidence interval: 1.10-3.83). Logistic regression analysis using
      A171S/169 C-->T haplotypes as the allelic markers showed that among AA wild-type
      homozygotes for A171S mutation, this C-->T nucleotide transition in codon 169 was
      associated with a 2.42 times increased risk (odds ratio = 2.42; 95% confidence
      interval: 1.26-4.63). This initial observation of an association between a
      polymorphism in the SLC10A2 gene and the risk of colorectal adenomatous polyps
      would, if confirmed by other studies, support the role of bile acids in the
      carcinogenesis of colorectal cancer.

PMID- 11535544
TI  - Markers of insulin resistance and colorectal cancer mortality.
AB  - A link between insulin metabolism and colorectal cancer has been hypothesized,
      supported by a series of potential physiological mechanisms, and confirmed by a
      number of reports in experimental animals. However, the evidence in humans is
      limited and mostly indirect. The aim of the present report is to analyze whether
      individuals with a cluster of metabolic abnormalities associated with
      abnormalities in insulin metabolism experience higher mortality for colorectal
      cancer than those without this cluster of metabolic abnormalities. A total of
      21,311 men and 15,991 women 20-69 years of age were followed-up for an average of
      7 years as part of the Risk Factors and Life Expectancy Project, a pooling of a
      number of epidemiological studies conducted in Italy. Our analyses indicate that
      participants with high levels of blood glucose and a cluster of metabolic
      abnormalities linked to insulin resistance experienced a significant increased
      risk of colorectal cancer mortality compared with participants without the
      cluster. For the presence of the cluster of metabolic abnormalities, the
      calculated hazard ratios and 95% CIs were 2.96 (1.05-8.31) for men, 2.71 (0.59
      12.50) for women, and 2.99 (1.27-7.01) when both sexes were combined. These
      associations were independent from the potential confounding effect of age,
      drinking of alcoholic beverages, and smoking. Our findings are supportive of the
      hypotheses that glucose metabolism hyperinsulinemia, insulin resistance, and
      metabolic abnormalities associated with it may play a significant role in the
      etiology of colorectal cancer.

PMID- 11535545
TI  - Cyp17 promoter variant associated with prostate cancer aggressiveness in African
      Americans.
AB  - Androgens play an important role in the etiology of prostate cancer. The CYP17
      gene encodes the cytochrome P450c17alpha enzyme, which is the rate-limiting
      enzyme in androgen biosynthesis. A T to C polymorphism in the 5' promoter region
      has recently been associated with prostate cancer. However, contradictory data
      exists concerning the risk allele. To investigate further the involvement of the
      CYP17 variant with prostate cancer, we typed the polymorphism in three different
      populations and evaluated its association with prostate cancer and clinical
      presentation in African Americans. We genotyped the CYP17 polymorphism in
      Nigerian (n = 56), European-American (n = 74), and African-American (n = 111)
      healthy male volunteers, along with African-American men affected with prostate
      cancer (n = 71), using pyrosequencing. Genotype and allele frequencies did not
      differ significantly across the different control populations. African-American
      men with the CC CYP17 genotype had an increased risk of prostate cancer (odds
      ratio, 2.8; 95% confidence interval, 1.0-7.4) compared with those with the TT
      genotype. A similar trend was observed between the homozygous variant genotype in
      African-American prostate cancer patients and clinical presentation. The CC
      genotype was significantly associated with higher grade and stage of prostate
      cancer (odds ratio, 7.1; 95% confidence interval, 1.4-36.1). The risk did not
      differ significantly by family history or age. Our results suggest that the C
      allele of the CYP17 polymorphism is significantly associated with increased
      prostate cancer risk and clinically advanced disease in African Americans.

PMID- 11535546
TI  - Potent induction of phase 2 enzymes in human prostate cells by sulforaphane.
AB  - Two population-based, case-control studies have documented reduced risk of
      prostate cancer in men who consume cruciferous vegetables. Cruciferae contain
      high levels of the isothiocyanate sulforaphane. Sulforaphane is known to bolster
      the defenses of cells against carcinogens through up-regulation of enzymes of
      carcinogen defense (phase 2 enzymes). Prostate cancer is characterized by an
      early and near universal loss of expression of the phase 2 enzyme glutathione S
      transferase (GST)-pi. We tested whether sulforaphane may act in prostatic cells
      by increasing phase 2 enzyme expression. The human prostate cancer cell lines
      LNCaP, MDA PCa 2a, MDA PCa 2b, PC-3, and TSU-Pr1 were treated with 0.1-15 microM
      sulforaphane in vitro. LNCaP was also treated with an aqueous extract of broccoli
      sprouts. Quinone reductase enzymatic activity, a surrogate of global phase 2
      enzyme activity, was assayed by the menadione-coupled reduction of tetrazolium
      dye. Expression of NQO-1, GST-alpha, gamma-glutamylcysteine synthetase-heavy and 
      light chains, and microsomal GST was assessed by Northern blot analysis.
      Sulforaphane and broccoli sprout extract potently induce quinone reductase
      activity in cultured prostate cells, and this induction appears to be mediated by
      increased transcription of the NQO-1 gene. Sulforaphane also induces expression
      of gamma-glutamylcysteine synthetase light subunit but not the heavy subunit, and
      this induction is associated with moderate increases in intracellular glutathione
      levels. Microsomal and alpha-class glutathione transferases were also induced
      transcriptionally. Sulforaphane induces phase 2 enzyme expression and activity
      significantly in human prostatic cells. This induction is accompanied by, but not
      because of, increased intracellular glutathione synthesis. Our findings may help
      explain the observed inverse correlation between consumption of cruciferae and
      prostate cancer risk.

PMID- 11535547
TI  - A single nucleotide polymorphism in the 5' untranslated region of RAD51 and risk
      of cancer among BRCA1/2 mutation carriers.
AB  - RAD51 colocalizes with both BRCA1 and BRCA2, and genetic variants in RAD51 would
      be candidate BRCA1/2 modifiers. We searched for RAD51 polymorphisms by sequencing
      20 individuals. We compared the polymorphism allele frequencies between female
      BRCA1/2 mutation carriers with and without breast or ovarian cancer and between
      population-based ovarian cancer cases with BRCA1/2 mutations to cases and
      controls without mutations. We discovered two single nucleotide polymorphisms
      (SNPs) at positions 135 g-->c and 172 g-->t of the 5' untranslated region. In an
      initial group of BRCA1/2 mutation carriers, 14 (21%) of 67 breast cancer cases
      carried a "c" allele at RAD51:135 g-->c, whereas 8 (7%) of 119 women without
      breast cancer carried this allele. In a second set of 466 mutation carriers from
      three centers, the association of RAD51:135 g-->c with breast cancer risk was not
      confirmed. Analyses restricted to the 216 BRCA2 mutation carriers, however,
      showed a statistically significant association of the 135 "c" allele with the
      risk of breast cancer (adjusted odds ratio, 3.2; 95% confidence limit, 1.4-40).
      BRCA1/2 mutation carriers with ovarian cancer were only about one half as likely
      to carry the RAD51:135 g-->c SNP. Analysis of the RAD51:135 g-->c SNP in 738
      subjects from an Israeli ovarian cancer case-control study was consistent with a
      lower risk of ovarian cancer among BRCA1/2 mutation carriers with the "c" allele.
      We have identified a RAD51 5' untranslated region SNP that may be associated with
      an increased risk of breast cancer and a lower risk of ovarian cancer among BRCA2
      mutation carriers. The biochemical basis of this risk modifier is currently
      unknown.

PMID- 11535548
TI  - Effect of raloxifene on breast cancer cell Ki67 and apoptosis: a double-blind,
      placebo-controlled, randomized clinical trial in postmenopausal patients.
AB  - PURPOSE: Raloxifene is a selective estrogen receptor (ER) modulator approved for
      prevention and treatment of postmenopausal osteoporosis. This is an exploratory
      study of raloxifene in primary breast cancer patients. EXPERIMENTAL DESIGN:
      Postmenopausal women (50-80 years of age), with histological or cytological
      diagnosis of stage I or II primary breast cancer, were randomly assigned to 14
      days of placebo, 60 mg/day raloxifene, or 300 mg twice daily (600 mg/day) of
      raloxifene. A core biopsy of the primary tumor was obtained before therapy, and a
      representative sample of the excised tumor was obtained from the operative
      specimen after treatment. Paired baseline and endpoint biopsies from each patient
      were analyzed for Ki67, apoptosis, and estrogen and progesterone receptors.
      Treatment group differences in efficacy measurements were primarily evaluated for
      baseline-to-endpoint change and percentage change using a one-way ANOVA with
      treatment as the fixed effect. RESULTS: Of 167 enrolled patients, 143 had
      evaluable efficacy data. Most breast cancer cases were invasive (98.6%), stage I
      (76.6%), and ER-positive (83.2%). In patients with ER-positive tumors, Ki67
      increased 7% from baseline on placebo and decreased by 21% on 60 mg/day
      raloxifene (P = 0.015 versus placebo) and by 14% on 600 mg/day raloxifene (P =
      0.064 versus placebo). Raloxifene did not affect apoptosis. ER decreased
      significantly with 60 mg/day or 600 mg/day raloxifene compared with placebo (P <
      0.01 for each comparison). Raloxifene had no statistically significant effects on
      Ki67 among patients with ER-negative tumors. There were no treatment differences
      in adverse events. CONCLUSION: In this exploratory trial, 60 mg/day raloxifene
      showed a significant antiproliferative effect in ER-positive breast cancer,
      demonstrated by the decrease in Ki67, with no effect in ER-negative cancer. This
      provides support for raloxifene having a breast cancer preventive effect in
      postmenopausal women.

PMID- 11535549
TI  - Correlation between tamoxifen elimination and biomarker recovery in a primary
      prevention trial.
AB  - We have shown previously that a reduction from the conventional dose of tamoxifen
      is associated with a comparable modulation of circulating biomarkers, including
      insulin-like growth factor-I and cholesterol. In the present study, we have
      correlated serum tamoxifen elimination with biomarker recovery in healthy
      subjects completing a 5-year intervention period. Tamoxifen, N
      desmethyltamoxifen, and biomarker levels were measured at 0 (baseline), 2, 4, and
      6 weeks after completion of treatment in 23 healthy postmenopausal women
      allocated to tamoxifen 20 mg/day and in 6 women allocated to placebo. Mean (+/
      SD) serum tamoxifen and N-desmethyltamoxifen concentrations were, respectively,
      141 +/- 50 and 226 +/- 77 ng/ml at baseline, 36 +/- 19 and 99 +/- 46 at 2 weeks,
      20 +/- 15 and 61 +/- 37 at 4 weeks, and 12 +/- 9 and 36 +/- 26 at 6 weeks. Serum
      tamoxifen and N-desmethyltamoxifen half-lives were 9 and 13 days, respectively.
      Body mass index was associated positively with drug's serum half-life. Compared
      with baseline values, the percentage increase in total cholesterol, low-density
      lipoprotein cholesterol, and insulin-like growth factor-I 4 weeks after treatment
      completion was 5, 9, and 14%, respectively. No change during the 6-week period
      was observed in the placebo arm. Our findings indicate that the biomarker
      recovery is slower than serum tamoxifen elimination, suggesting that low
      tamoxifen concentrations may still exert a biological effect. In addition, the
      prolonged half-life of tamoxifen and metabolite provides the rationale for a
      weekly administration of the drug in a preventive context. However, the clinical
      implications of our findings remain to be defined.

PMID- 11535550
TI  - Polymorphisms of two fucosyltransferase genes (Lewis and Secretor genes)
      involving type I Lewis antigens are associated with the presence of anti
      Helicobacter pylori IgG antibody.
AB  - Helicobacter pylori attach to the gastric mucosa with adhesin, which binds to
      Lewis b (Le(b)) or H type I carbohydrate structures. The Secretor (Se) gene and
      Lewis (Le) gene are involved in type I Le antigen synthesis. The present study
      was performed to investigate the possibility that Se and Le gene polymorphisms
      alter the risk of H. pylori infection. Two hundred thirty-nine participants were
      genotyped for Se and Le and tested for the presence of anti-H. pylori IgG
      antibodies. Using the normal gastric mucosa from 60 gastric cancer patients, we
      assessed immunohistochemically whether type I Le antigen expression depended on
      the Se and Le genotypes. The H. pylori infection rate was positively associated
      with the number of Se alleles (se/se group, 45.1%; Se/se group, 64.6%; and Se/Se
      group, 73.3%) and negatively associated with the number of Le alleles (le/le
      group, 76.4%; Le/le group, 68.3%; and Le/Le group, 55.6%). When the subjects were
      classified into three groups [low risk, (se/se, Le/Le) genotype; high risk,
      (Se/Se, le/le), (Se/Se, Le/le), and (Se/se, le/le) genotypes; moderate risk,
      other than low- or high-risk group], the odds ratio relative to the low-risk
      group was 3.30 (95% confidence interval, 1.40-7.78) for the moderate-risk group
      and 10.33 (95% confidence interval, 3.16-33.8) for the high-risk group.
      Immunohistochemical analysis supported the finding that Se and Le genotypes
      affected the expression of H. pylori adhesin ligands. We conclude that Se and Le
      genotypes affect susceptibility to H. pylori infection.

PMID- 11535551
TI  - Iodine and thyroid cancer risk among women in a multiethnic population: the Bay
      Area Thyroid Cancer Study.
AB  - Research on the relationship between iodine exposure and thyroid cancer risk is
      limited, and the findings are inconclusive. In most studies, fish/shellfish
      consumption has been used as a proxy measure of iodine exposure. The present
      study extends this research by quantifying dietary iodine exposure as well as
      incorporating a biomarker of long-term (1 year) exposure, i.e., from toenail
      clippings. This study is conducted in a multiethnic population with a wide
      variation in thyroid cancer incidence rates and substantial diversity in
      exposure. Women, ages 20-74, residing in the San Francisco Bay Area and diagnosed
      with thyroid cancer between 1995 and 1998 (1992-1998 for Asian women) were
      compared with women selected from the general population via random digit
      dialing. Interviews were conducted in six languages with 608 cases and 558
      controls. The established risk factors for thyroid cancer were found to increase
      risk in this population: radiation to the head/neck [odds ratio (OR), 2.3; 95%
      confidence interval (CI), 0.97-5.5]; history of goiter/nodules (OR, 3.7; 95% CI,
      2.5-5.6); and a family history of proliferative thyroid disease (OR, 2.5; 95% CI,
      1.6-3.8). Contrary to our hypothesis, increased dietary iodine, most likely
      related to the use of multivitamin pills, was associated with a reduced risk of
      papillary thyroid cancer. This risk reduction was observed in "low-risk" women
      (i.e., women without any of the three established risk factors noted above; OR,
      0.53; 95% CI, 0.33-0.85) but not in "high-risk" women, among whom a slight
      elevation in risk was seen (OR, 1.4; 95% CI, 0.56-3.4). However, no association
      with risk was observed in either group when the biomarker of exposure was
      evaluated. In addition, no ethnic differences in risk were observed. The authors
      conclude that iodine exposure appears to have, at most, a weak effect on the risk
      of papillary thyroid cancer.

PMID- 11535552
TI  - Single-cell gel (comet) assay detects primary DNA damage in nonneoplastic
      urothelial cells of smokers and ex-smokers.
AB  - A protocol for DNA damage assessment by the single-cell gel (SCG)/comet assay in
      human urinary bladder washing cells was established. Modifications of the
      standard alkaline protocol included an increase to 2% of sodium sarcosinate in
      the lysis solution, a reduction in the glass-slide area for comet analysis, and a
      cutoff value for comet head diameter of at least 30 microm, to exclude
      contaminating leukocytes. Distinguishing cell populations is crucial, because
      significant differential migration was demonstrated for transitional and
      nontransitional cells, phenomena that may confound the results. When applying the
      modified protocol to urinary bladder cells from smokers without urinary bladder
      neoplasia, it was possible to detect a significant (P = 0.03) increase in DNA
      damage as depicted by the tail moment (6.39 +/- 3.23; mean +/- 95% confidence
      interval; n = 18) when compared with nonsmokers (1.94 +/- 1.41; n = 12). No
      significant differences were observed between ex-smokers and current smokers
      regarding comet parameters. Inflammation was not a confounding factor, but DNA
      migration increased significantly with age in nonsmokers (r = 0.68; P = 0.014).
      Thus, age matching should be a concern when transitional cells are analyzed in
      the SCG assay. As it is well known, DNA damage may trigger genomic instability, a
      crucial step in carcinogenesis. Therefore, the present data directly support the
      classification of individuals with smoking history as patients at high risk for
      urinary bladder cancer.

PMID- 11535553
TI  - Second primary ovarian cancer among women diagnosed previously with cancer.
AB  - This study assessed the risk of second primary ovarian cancer among United States
      women diagnosed previously with invasive cancer. We analyzed data from cancer
      registries participating in the Surveillance, Epidemiology, and End Results
      program for women diagnosed with invasive cancer between 1973 and 1996. We
      calculated the risk [observed (O)/expected numbers (E)] of second primary ovarian
      cancer by cancer site and age at diagnosis of first primary cancer (<50 years and
      > or =50 years), race (all, white, and black), and years since first cancer (0-4,
      5-9, 10-14, and 15-24 years). Statistical tests and 95% confidence intervals (CI)
      assumed a Poisson distribution. A significantly increased risk of ovarian cancer
      was found for women who were aged <50 years at diagnosis with melanoma (O/E =
      3.5, 95% CI = 2.1-5.5) or cancer of the breast (O/E = 6.0, 95% CI = 4.9-7.2),
      cervix (O/E = 4.2, 95% CI = 2.6-6.3), corpus uteri (O/E = 11.9, 95% CI = 7.3
      18.4), colon (O/E = 17.9, 95% CI = 11.1-27.3), or ovary (O/E = 4.9, 95% CI = 2.7
      8.2). No increased risk was found for women aged > or =50 years. Ovarian cancer
      risk remained elevated after these first primary cancers 5-9 years after
      diagnosis; for breast and colon cancer, risk remained elevated 15-24 years after
      diagnosis. Women > or =50 years at diagnosis with melanoma or cancer of the
      cervix, corpus uteri, ovary, rectum, or lung and bronchus were at a decreased
      risk for second primary ovarian cancer. Ovarian cancer risk is higher than
      expected for women who were diagnosed with certain types of cancer at <50 years
      of age.

PMID- 11535554
TI  - Family history and risk of renal cell carcinoma.
AB  - Few analytical epidemiological studies have investigated family history (FH) of
      urinary tract cancers as a potential risk factor for renal cell carcinoma (RCC).
      A population-based case-control study involving 550 non-Asian RCC patients 25 to
      74 years of age and an equal number of sex-, age-, and race-matched neighborhood
      controls was conducted in Los Angeles, California. Detailed information on FH of
      cancer, medical and medication histories, and other life-style factors was
      obtained through in-person interviews. Having a first-degree relative with kidney
      cancer was associated with a significantly increased risk of RCC [odds ratio
      (OR), 2.5; 95% confidence interval (CI), 1.04-5.9] after adjustment for potential
      confounding factors. Having a first and/or second-degree relative with kidney
      cancer was similarly associated with an increased risk of RCC (OR, 2.9; 95% CI,
      1.4-6.3). Risk factors for RCC identified in the Los Angeles study include
      cigarette smoking, chronic obesity, history of hypertension, regular use of
      analgesics and amphetamines, intake of cruciferous vegetables (protective), and
      history of hysterectomy. None of the above risk factor-RCC associations differed
      significantly between RCC cases with and without a FH of kidney cancer. A FH of
      urinary tract cancers other than kidney cancer was not associated with RCC risk
      (OR, 0.7; 95% CI, 0.3-1.7). A FH of nonurinary tract cancers also was unrelated
      to RCC risk (OR, 1.1; 95% CI, 0.9-1.5).

PMID- 11535555
TI  - Determinants of DNA yield and quality from buccal cell samples collected with
      mouthwash.
AB  - Buccal cells are becoming an important source of genomic DNA in epidemiological
      studies, but little is known about the effect of different sampling conditions on
      DNA quality and yield. We used a mouthwash protocol to collect six daily buccal
      cell samples from 35 healthy volunteers. Twenty-four individuals (six men and 18
      women) correctly completed the protocol and were included in paired analyses to
      determine whether "swish" time (30 s versus 60 s), toothbrushing before
      collection, or lag time between collection and DNA extraction (1 day versus 5,
      10, or 30 days at room temperature) would affect sample quality and yield. Total
      DNA, human-specific DNA (hDNA), degradation of DNA, and ability to amplify by PCR
      were determined. hDNA yield did not significantly vary by "swish" time. However,
      toothbrushing 1 h before sample collection reduced the amount of hDNA by nearly
      40% (34 microg versus 21 microg; P = 0.06). Median hDNA yields for samples that
      were held for 1, 5, 10, and 30 days before extraction were 32 microg (range, 4
      196), 32 microg (2-194), 23 microg (3-80), and 21 microg (5-56), respectively.
      The 10- and 30-day samples had significantly less hDNA than those processed after
      1 day (P = 0.01). PCR success rates for beta-globin gene fragments of length 268
      bp, 536 bp, and 989 bp were 94% or better, and high molecular weight DNA (>23 kb)
      was found in all but one sample. These results suggest that buccal cells should
      be collected before brushing teeth and processed within 5 days of collection to
      maximize hDNA yield.

PMID- 11535556
TI  - TP53 polymorphism, HPV infection, and risk of cervical cancer.
AB  - The role of a polymorphism at position 72 of the tumor suppressor gene TP53 in
      the development of cervical cancer is not well established. The arginine variant
      of the p53 protein could be more susceptible to degradation by human
      papillomavirus (HPV) E6 protein than the protein containing proline. Recent
      studies show controversial results. We investigated a possible association
      between TP53 polymorphism and cervical cancer in a Peruvian population with high
      prevalence of HPV infection. HPV status and TP53 polymorphism were determined for
      119 cases of invasive cervical cancer and 127 control women from Peru. HPV
      infection was detected by PCR of cervical cells or tumor biopsies. For
      determination of TP53 polymorphism, exon 4 of the TP53 gene was amplified by PCR,
      and DNA was subsequently subjected to restriction enzyme digest. Associations
      between TP53 polymorphism, HPV infection, and cervical cancer were assessed using
      logistic regression. Women homozygotes for arginine had a 2.2-fold increased risk
      (95% confidence interval: 0.6-7.6) for cervical cancer. The odds ratio for women
      heterozygotes for Arg/Pro was 3.5 (95% confidence interval: 0.9-14). Similarly
      increased risks were found when restricting analysis to HPV-positive women only.
      The distribution of TP53 genotypes in this Peruvian population was comparable
      with that found in Caucasians. Our results cannot rule out an association between
      the TP53 polymorphism at codon 72, HPV infection, and the etiology of cervical
      cancer.

PMID- 11535558
TI  - Folate and nitrate-induced endothelial dysfunction: a simple treatment for a
      complex pathobiology.

PMID- 11535559
TI  - Dynamic regulation of the extracellular matrix after mechanical unloading of the
      failing human heart: recovering the missing link in left ventricular remodeling.

PMID- 11535560
TI  - Cardiac sodium channel gene mutations and sudden infant death syndrome:
      confirmation of proof of concept?

PMID- 11535561
TI  - Anti-tumor necrosis factor-alpha antibody limits heart failure in a transgenic
      model.
AB  - BACKGROUND: - Tumor necrosis factor (TNF)-alpha has been implicated in the
      pathophysiology of congestive heart failure. A strain of transgenic mice (TNF1.6)
      with cardiac-specific overexpression of TNF-alpha develop congestive heart
      failure. METHODS AND RESULTS: To determine the effect of anti-TNF-alpha therapy
      in this model, we studied 3 groups: TNF1.6 mice treated with saline, wild-type
      mice treated with saline, and TNF1.6 mice treated with TNF-alpha neutralizing
      antibody (cV1q) from 6 to 12 weeks of age. We used echocardiography to compare
      cardiac hypertrophy, function, and catecholamine response at 12 weeks of age
      versus baseline (6 weeks). cV1q treatment did not limit cardiac hypertrophy, but
      it significantly improved basal fractional shortening and responsiveness to beta
      adrenergic stimulation, and it limited development of cardiac dilation.
      CONCLUSIONS: Blockade of TNF-alpha bioactivity by antibody therapy may both
      preserve cardiac function and partially reverse pathological changes in
      congestive heart failure.

PMID- 11535562
TI  - Protection against autoimmune myocarditis by gene transfer of interleukin-10 by
      electroporation.
AB  - BACKGROUND: Although immunosuppressive therapy for myocarditis has attracted a
      great deal of attention, its effectiveness is controversial. Interleukin (IL)-10
      has a variety of immunomodulatory properties. Among the nonviral techniques for
      gene transfer in vivo, the direct injection of plasmid DNA into muscle is simple,
      inexpensive, and safe. METHODS AND RESULTS: We examined the applicability of
      murine IL-10 (mIL-10) gene transfer to the treatment of rats with experimental
      autoimmune myocarditis. Nine-week-old Lewis rats were inoculated with pig myosin
      (day 0). A plasmid vector expressing mIL-10 cDNA (800 microgram per rat) was
      transferred into the tibialis anterior muscles by electroporation 3 times (5 days
      before immunization and at days 4 and 13); control rats received empty plasmid.
      Electroporation increased the serum mIL-10 levels to >250 pg/mL. The 21-day
      survival rate in rats treated with mIL-10 cDNA was higher (15 of 15; 100%) than
      that of the control group (9 of 15; 60%). Furthermore, mIL-10 treatment
      significantly attenuated myocardial lesions and improved hemodynamic parameters.
      CONCLUSIONS: These findings showed that gene transfer into muscle by
      electroporation in vivo is an effective means of delivery of IL-10 for the
      treatment of autoimmune myocarditis.

PMID- 11535563
TI  - Transmural extent of acute myocardial infarction predicts long-term improvement
      in contractile function.
AB  - BACKGROUND: Previous animal studies have demonstrated that the transmural extent
      of acute myocardial infarction defined by contrast-enhanced MRI (ceMRI) relates
      to early restoration of flow and future improvements in contractile function. We
      tested the hypothesis that ceMRI would have similar predictive value in humans.
      METHODS AND RESULTS: Twenty-four patients who presented with their first
      myocardial infarction and were successfully revascularized underwent cine and
      ceMRI of their heart within 7 days (scan 1) of the peak MB band of creatine
      kinase. Cine MRI was repeated 8 to 12 weeks later (scan 2). The transmural extent
      of infarction on scan 1 and wall thickening on both scans were determined using a
      72-segment model. A total of 524 of 1571 segments (33%) were dysfunctional on
      scan 1. Improvement in segmental contractile function on scan 2 was inversely
      related to the transmural extent of infarction on scan 1 (P=0.001). Improvement
      in global contractile function, as assessed by ejection fraction and mean wall
      thickening score, was not predicted by peak creatine kinase-MB (P=0.66) or by
      total infarct size, as defined by MRI (P=0.70). The best predictor of global
      improvement was the extent of dysfunctional myocardium that was not infarcted or
      had infarction comprising <25% of left ventricular wall thickness (P<0.005 for
      ejection fraction, P<0.001 for mean wall thickening score). CONCLUSION: In
      patients with acute myocardial infarction, the transmural extent of infarction
      defined by ceMRI predicts improvement in contractile function.

PMID- 11535564
TI  - Coronary heart disease prediction from lipoprotein cholesterol levels,
      triglycerides, lipoprotein(a), apolipoproteins A-I and B, and HDL density
      subfractions: The Atherosclerosis Risk in Communities (ARIC) Study.
AB  - BACKGROUND: Despite consensus on the need for blood cholesterol reductions to
      prevent coronary heart disease (CHD), available evidence on optimal cholesterol
      levels or the added predictive value of additional lipids is sparse. METHODS AND
      RESULTS: After 10 years follow-up of 12 339 middle-aged participants free of CHD
      in the Atherosclerosis Risk in Communities Study (ARIC), 725 CHD events occurred.
      The lowest incidence was observed in those at the lowest LDL cholesterol (LDL-C)
      quintile, with medians of 88 mg/dL in women and 95 mg/dL in men, and risk
      accelerated at higher levels, with relative risks (RRs) for the highest quintile
      of 2.7 in women and 2.5 in men. LDL-C, HDL-C, lipoprotein(a) [Lp(a)], and in
      women but not men, triglycerides (TG) were all independent CHD predictors,
      providing an RR, together with blood pressure, smoking, and diabetes, of 13.5 in
      women and 4.9 in men. Lp(a) was less significant in blacks than whites.
      Prediction was not enhanced by HDL-C density subfractions or apolipoproteins
      (apo) A-I or B. Despite strong univariate associations, apoB did not contribute
      to risk prediction in subgroups with elevated TG, with lower LDL-C, or with high
      apoB relative to LDL-C. CONCLUSIONS: Optimal LDL-C values are <100 mg/dL in both
      women and men. LDL-C, HDL-C, TG, and Lp(a), without additional apolipoproteins or
      lipid subfractions, provide substantial CHD prediction, with much higher RR in
      women than men.

PMID- 11535565
TI  - Role of endothelin-1 in the active constriction of human atherosclerotic coronary
      arteries.
AB  - BACKGROUND: Atherosclerotic coronary arteries are prone to constriction but the
      underlying causes are incompletely understood. We tested the hypothesis that
      endothelin-1 (ET-1), a potent vasoconstrictor, contributes to the heightened tone
      of atherosclerotic human coronary arteries. METHODS AND RESULTS: In 8 patients
      with coronary artery disease (CAD) and 8 patients with angiographically smooth
      coronary arteries (normal), we infused BQ-123, an antagonist of the ET(A)
      receptor, into a major coronary artery (infused artery) at 40 nmol/min for 60
      minutes. The infused artery in the CAD patients contained a >50% stenosis. Using
      quantitative angiography, we compared the dilation of the infused artery with
      another, noninfused coronary artery. To estimate the magnitude of the
      contribution of ET-1 to coronary tone, we compared the dilation to BQ-123 with
      that elicited by intracoronary nitroglycerin (200 microgram). BQ-123 induced
      significant dilation in the normal arteries (7.3% at 60 minutes, P<0.001 versus
      noninfused arteries) and a greater dilation in the CAD arteries (16.3% at 60
      minutes, P<0.001 versus infused normal arteries). The dilation at stenoses was
      particularly pronounced (21.6% at 60 minutes, P<0.001 versus infused CAD
      arteries). Compared with the dilation from nitroglycerin, ET-1 contributed to 39%
      of the coronary tone in normal arteries, 74% of tone in CAD arteries, and 106% of
      tone at stenoses (P<0.01). CONCLUSIONS: ET-1 accounts for nearly all the resting
      tone in atherosclerotic coronary arteries, especially at stenoses. Inhibitors of
      ET-1, by relieving constriction, may significantly lessen the hemodynamic
      significance of coronary stenoses and thereby reduce myocardial ischemia.

PMID- 11535566
TI  - Folic acid prevents nitroglycerin-induced nitric oxide synthase dysfunction and
      nitrate tolerance: a human in vivo study.
AB  - BACKGROUND: In healthy humans, continuous treatment with nitroglycerin (GTN)
      causes nitric oxide synthase dysfunction, probably through the reduced
      bioavailability of tetrahydrobiopterin. Recent studies proposed that folic acid
      is involved in the regeneration of tetrahydrobiopterin in different disease
      states. Therefore, we investigated whether folic acid administration would
      prevent this phenomenon. We also sought to determine if folic acid
      supplementation could prevent the development of tolerance to GTN. METHODS AND
      RESULTS: On the first visit, 18 healthy male volunteers (aged 19 to 32 years)
      were randomized to receive either oral folic acid (10 mg once a day) or placebo
      for 1 week in a double-blind designed study. All subjects also received
      continuous transdermal GTN (0.6 mg/h). On the second visit, forearm blood flow
      was measured with venous occlusion strain gauge plethysmography in response to
      incremental infusions of acetylcholine (7.5, 15, and 30 microgram/min), N
      monomethyl-L-arginine (1, 2, and 4 micromol/min), and GTN (11 and 22 nmol/min).
      Folic acid prevented GTN-induced endothelial dysfunction, as assessed by
      responses to intraarterial acetylcholine and N-monomethyl-L-arginine (P<0.01).
      Moreover, in the subjects treated with folic acid plus transdermal GTN, responses
      to intraarterial GTN were significantly greater than those observed after
      transdermal GTN plus placebo (P<0.05). CONCLUSION: Our data demonstrate that
      supplemental folic acid prevents both nitric oxide synthase dysfunction induced
      by continuous GTN and nitrate tolerance in the arterial circulation of healthy
      volunteers. We hypothesize that the reduced bioavailability of
      tetrahydrobiopterin is involved in the pathogenesis of both phenomena. Our
      results confirm the view that oxidative stress contributes to nitrate tolerance.

PMID- 11535567
TI  - Oxidative stress and platelet activation in homozygous homocystinuria.
AB  - BACKGROUND: Severe hyperhomocysteinemia due to cystathionine beta-synthase
      deficiency (CbetaSD) is associated with early atherothrombotic vascular disease.
      Homocysteine may exert its effects by promoting oxidative damage. In the present
      study, we investigated whether in vivo formation of 8-iso-prostaglandin (PG)
      F(2alpha), a platelet-active product of arachidonic acid peroxidation, is
      enhanced in CbetaSD and whether it correlates with in vivo platelet activation,
      as reflected by thromboxane (TX) metabolite excretion. METHODS AND RESULTS: Urine
      and blood samples were obtained from patients with homozygous CbetaSD (n=13) and
      age-matched healthy subjects. Urinary 8-iso-PGF(2alpha) excretion was
      significantly higher in CbetaSD patients than in control subjects (640+/-384
      versus 213+/-43 pg/mg creatinine; P=0.0015) and correlated with plasma
      homocysteine (rho=0.398, P=0.0076). Similarly, urinary 11-dehydro-TXB(2)
      excretion was enhanced in CbetaSD (1166+/-415 versus 324+/-72 pg/mg creatinine;
      P=0.0015) and correlated with urinary 8-iso-PGF(2alpha) (rho=0.362, P=0.0153).
      Vitamin E supplementation (600 mg/d for 2 weeks) was associated with a
      statistically significant increase in its plasma levels (from 16.6+/-4.6 to
      40.4+/-8.7 micromol/L, P=0.0002) and with reductions in 8-iso-PGF(2alpha) (from
      790+/-159 to 559+/-111 pg/mg creatinine, P=0.018) and 11-dehydro-TXB(2) (from
      1273+/-383 to 913+/-336 pg/mg creatinine, P=0.028). A statistically significant
      inverse correlation was found between urinary 8-iso-PGF(2alpha) and plasma
      vitamin E levels (rho=-0.745, P=0.0135). CONCLUSIONS: The results of the present
      study suggest that enhanced peroxidation of arachidonic acid to form bioactive
      F(2)-isoprostanes may represent an important mechanism linking
      hyperhomocysteinemia and platelet activation in CbetaSD patients. Moreover, they
      provide a rationale for dose-finding studies of vitamin E supplementation in this
      setting.

PMID- 11535568
TI  - Microvascular dysfunction in chronic total coronary occlusions.
AB  - BACKGROUND: Microvascular dysfunction is defined as reduced coronary flow reserve
      in the absence of an epicardial stenosis. This study determined its prevalence
      and relation to regional myocardial function in chronic total coronary occlusions
      (TCO). METHODS AND RESULTS: After recanalization and stenting of a TCO (duration,
      >4 weeks) in 42 patients, coronary flow velocity reserve (CFVR) was measured by
      intracoronary Doppler. In a subset of 27 patients, intracoronary pressure was
      recorded to obtain the fractional flow reserve (FFR). In 21 patients, the CFVR
      was reassessed after 24 hours. CFVR was <2.0 in 55% of all patients. In the
      subgroup with simultaneous pressure recordings, 52% of patients showed a CFVR<2.0
      and a FFR>/=0.75, indicating microvascular dysfunction. Both reduced CFVR and
      reduced FFR occurred in only 2 patients (7.7%). CFVR and FFR were not correlated
      (r=0.03). A low CFVR was associated with a higher baseline average peak velocity
      (35.6+/-16.6 versus 22.4+/-11.5 cm/s; P=0.006). Doppler parameters did not change
      within 24 hours. Regional dysfunction had no influence on CFVR. Patients with
      diabetes and/or hypertension had a lower CFVR than those without this comorbidity
      (1.86+/-0.69 versus 2.36+/-0.45; P<0.05). CONCLUSIONS: Microvascular dysfunction
      was observed in 55% of TCOs, independent of the impairment of regional myocardial
      function. Dysfunction was observed more often in patients with diabetes and
      hypertension. Neither CFVR or FFR alone is appropriate for assessing angioplasty
      results in patients with a TCO; CFVR should be combined with FFR to differentiate
      microvascular dysfunction from residual coronary stenosis or diffuse disease.

PMID- 11535569
TI  - Previous cytomegalovirus infection and restenosis after coronary stent placement.
AB  - BACKGROUND: Reactivated cytomegalovirus may promote neointima formation after
      percutaneous coronary interventions by facilitating cell cycle progression
      through inhibition of the eukariotic tumor suppressor protein p53. This
      prospective study sought to investigate the effect of previous cytomegalovirus
      infection on restenosis after coronary stenting. METHODS AND RESULTS: In 551
      consecutive patients with successful stent placement, we determined
      cytomegalovirus IgG titers. Primary and secondary end points were the rate of
      angiographic restenosis at 6 months and the rate of target vessel reintervention
      at 1 year, respectively. Three hundred forty patients (62%) had a positive
      cytomegalovirus IgG titer. We obtained angiographic follow-up in 82% of all
      patients. Angiographic restenosis rate was 28.7% in patients with positive
      cytomegalovirus titers and 34.6% in patients with negative titers (P=0.18).
      Between the groups with and without positive cytomegalovirus titers, there were
      no significant differences in late lumen loss (1.16+/-0.90 mm and 1.23+/-0.86 mm,
      respectively, P=0.44). Target vessel reintervention was performed in 16.8% of the
      patients with positive cytomegalovirus titers and in 17.5% of those without
      (P=0.82). Even after correction for potential confounding variables by
      multivariate analysis, positive cytomegalovirus titers did not manifest as a
      predictor of angiographic restenosis (adjusted odds ratio [95% confidence
      interval], 0.78 [0.52 to 1.19]). CONCLUSIONS: Previous cytomegalovirus infection
      does not carry an increased risk of restenosis after stenting.

PMID- 11535570
TI  - Effects of calcium, inorganic phosphate, and pH on isometric force in single
      skinned cardiomyocytes from donor and failing human hearts.
AB  - BACKGROUND: During ischemia, the intracellular calcium and inorganic phosphate
      (P(i)) concentrations rise and pH falls. We investigated the effects of these
      changes on force development in donor and failing human hearts to determine if
      altered contractile protein composition during heart failure changes the
      myocardial response to Ca(2+), P(i), and pH. METHODS AND RESULTS: Isometric force
      was studied in mechanically isolated Triton-skinned single myocytes from left
      ventricular myocardium. Force declined with added P(i) to 0.33+/-0.02 of the
      control force (pH 7.1, 0 mmol/L P(i)) at 30 mmol/L P(i) and increased with pH
      from 0.64+/-0.03 at pH 6.2 to 1.27+/-0.02 at pH 7.4. Force dependency on P(i) and
      pH did not differ between donor and failing hearts. Incubation of myocytes in a
      P(i)-containing activating solution caused a potentiation of force, which was
      larger at submaximal than at maximal [Ca(2+)]. Ca(2+) sensitivity of force was
      similar in donor hearts and hearts with moderate cardiac disease, but in end
      stage failing myocardium it was significantly increased. The degree of myosin
      light chain 2 phosphorylation was significantly decreased in end-stage failing
      compared with donor myocardium, resulting in an inverse correlation between
      Ca(2+) responsiveness of force and myosin light chain 2 phosphorylation.
      CONCLUSIONS: Our results indicate that contractile protein alterations in human
      end-stage heart failure alter Ca(2+) responsiveness of force but do not affect
      the force-generating capacity of the cross-bridges or its P(i) and pH dependence.
      In end-stage failing myocardium, the reduction in force by changes in pH and
      [P(i)] at submaximal [Ca(2+)] may even be less than in donor hearts because of
      the increased Ca(2+) responsiveness.

PMID- 11535571
TI  - Downregulation of matrix metalloproteinases and reduction in collagen damage in
      the failing human heart after support with left ventricular assist devices.
AB  - BACKGROUND: Left ventricular assist device (LVAD) support of the failing heart
      induces salutary changes in myocardial structure and function. Matrix
      metalloproteinases (MMPs) are increased in the failing heart and are induced by
      stretch in cardiac cells in vitro. We hypothesized that mechanical unloading may
      affect LV plasticity by regulating MMPs and their substrates. METHODS AND
      RESULTS: LV samples were collected from patients with dilated cardiomyopathy
      (DCM, n=14) or ischemic cardiomyopathy (ICM, n=16) at the time of implantation of
      the LVAD and again during cardiac transplantation. MMP-1, -3, and -9 were
      measured by ELISA, MMP-2 and -9 gelatinolytic activity by gelatin zymography, and
      tissue inhibitors of metalloproteinases (TIMPs) by Western blot. Total soluble
      and insoluble collagens were separated by pepsin solubilization, and the contents
      were determined by quantification of hydroxyproline. The undenatured soluble
      collagen was measured by Sircol collagen assay. The results showed that MMP-1 and
      -9 were decreased, whereas TIMP-1 and -3 were increased, but there was no change
      in MMP-2 and -3 and TIMP-2 and -4 after LVAD support. The undenatured collagen
      was increased, with the ratio of undenatured to total soluble collagens increased
      in ICM and that of insoluble to total soluble collagens increased in DCM after
      LVAD support. CONCLUSIONS: The reduced MMPs and increased TIMPs and ratios of
      undenatured to total soluble collagens and insoluble to total soluble collagens
      after LVAD support suggest that reduced MMP activity diminished damage to the
      matrix. These changes may contribute to the functional recovery and LV plasticity
      after LVAD support.

PMID- 11535572
TI  - Different patterns of interatrial conduction in clockwise and counterclockwise
      atrial flutter.
AB  - BACKGROUND: The terms counterclockwise (CC) and clockwise (C) atrial flutter
      (Afl) are used to describe right atrial activation around the tricuspid valve in
      the left anterior oblique view. The manner in which the left atrium is activated,
      as reflected by coronary sinus (CS) recordings, has not been systematically
      evaluated. METHODS AND RESULTS: Nine patients with both CC and C Afl underwent
      electrophysiological study with CS recordings during both rhythms with the use of
      a decapolar catheter with the tip placed in the distal CS. Patterns of CS
      activation during each type of Afl as well as during during sinus rhythm were
      categorized into 1 of 3 patterns: sequential proximal-to-distal, sequential
      distal-to-proximal, and fused, indicating activation from different directions.
      In 7 of 9 patients, the pattern of CS activation in CC Afl and C Afl differed,
      with a proximal-to-distal pattern in CC Afl and a fused pattern in C Afl. In 2
      patients, pacing the high right atrial septum near the presumed site of
      Bachmann's bundle in sinus rhythm showed a similar fused pattern of CS
      activation. CONCLUSIONS: These results demonstrate different patterns of CS
      activation in CC Afl and C Afl in the majority of patients and are consistent
      with a model in which the left atrium is activated predominantly over Bachmann's
      bundle during C Afl and over the CS os in CC Afl. These findings may have
      implications for maintenance of Afl, interpretation of flutter wave morphology on
      surface ECG, and left atrial mechanical function in Afl.

PMID- 11535573
TI  - De novo mutation in the SCN5A gene associated with early onset of sudden infant
      death.
AB  - BACKGROUND: Congenital long QT syndrome (LQTS), a cardiac ion channel disease, is
      an important cause of sudden cardiac death. Prolongation of the QT interval has
      recently been associated with sudden infant death syndrome, which is the leading
      cause of death among infants between 1 week and 1 year of age. Available data
      suggest that early onset of congenital LQTS may contribute to premature sudden
      cardiac death in otherwise healthy infants. METHODS AND RESULTS: In an infant who
      died suddenly at the age of 9 weeks, we performed mutation screening in all known
      LQTS genes. In the surface ECG soon after birth, a prolonged QTc interval (600
      ms(1/2)) and polymorphic ventricular tachyarrhythmias were documented. Mutational
      analysis identified a missense mutation (Ala1330Pro) in the cardiac sodium
      channel gene SCN5A, which was absent in both parents. Subsequent genetic testing
      confirmed paternity, thus suggesting a de novo origin. Voltage-clamp recordings
      of recombinant A1330P mutant channel expressed in HEK-293 cells showed a positive
      shift in voltage dependence of inactivation, a slowing of the time course of
      inactivation, and a faster recovery from inactivation. CONCLUSIONS: In this
      study, we report a de novo mutation in the sodium channel gene SCN5A, which is
      associated with sudden infant death. The altered functional characteristics of
      the mutant channel was different from previously reported LQTS3 mutants and
      caused a delay in final repolarization. Even in families without a history of
      LQTS, de novo mutations in cardiac ion channel genes may lead to sudden cardiac
      death in very young infants.

PMID- 11535574
TI  - Taurine prevents the decrease in expression and secretion of extracellular
      superoxide dismutase induced by homocysteine: amelioration of homocysteine
      induced endoplasmic reticulum stress by taurine.
AB  - BACKGROUND: Hyperhomocysteinemia is an independent risk factor for
      atherosclerosis. Homocysteine has been shown to induce endoplasmic reticulum (ER)
      stress in vascular endothelial cells. ER stress is a condition in which
      glycoprotein trafficking is disrupted and unfolded proteins accumulate in the ER.
      ER molecular chaperons, such as GRP78, are induced and an ER resident kinase,
      PERK, is activated when cells are subjected to ER stress. Conversely, taurine is
      reported to have antiatherogenic effects by unknown mechanisms. To elucidate the
      mechanisms by which homocysteine induces atherosclerosis and taurine prevents it,
      we examined whether homocysteine and taurine affect the expression and secretion
      of extracellular superoxide dismutase (EC-SOD), a glycoprotein secreted from
      vascular smooth muscle cells (VSMCs) that protects the vascular wall from
      oxidative stress. METHODS AND RESULTS: We assessed the expression of EC-SOD and
      GRP78 mRNA in cultured rat VSMCs by Northern blot analysis. The EC-SOD protein
      secreted into the culture medium was examined by Western blot analysis.
      Homocysteine (5 mmol/L) and other ER stress inducers, including A23187, were
      found to decrease EC-SOD mRNA expression and protein secretion. Furthermore, they
      upregulated GRP78 mRNA expression and activated PERK. Taurine (0.5 to 10 mmol/L),
      conversely, prevented these actions induced by homocysteine. CONCLUSIONS:
      Homocysteine induces ER stress and reduces the secretion and expression of EC-SOD
      in VSMCs, leading to increased oxidative stress in the vascular wall. Taurine
      restores the secretion and expression of EC-SOD by ameliorating ER stress induced
      by homocysteine.

PMID- 11535575
TI  - Activated protein C prevents endotoxin-induced hypotension in rats by inhibiting
      excessive production of nitric oxide.
AB  - BACKGROUND: Excessive production of nitric oxide (NO) by the inducible isoform of
      NO synthase (iNOS) is critically involved in endotoxin (ET)-induced hypotension.
      Tumor necrosis factor-alpha (TNF-alpha) plays an important role in induction of
      iNOS. Because activated protein C (APC), a physiological anticoagulant, inhibits
      TNF-alpha production, it might prevent hypotension by inhibiting excessive
      production of NO. In this study, we examined this possibility using a rat model
      of septic shock. METHODS AND RESULTS: Intravenous administration of APC prevented
      both ET-induced hypotension and the increases in plasma levels of NO(2)(-)/NO(3)(
      ). The hypotension was also inhibited when APC was administered 30 minutes after
      ET administration. APC inhibited the increases in lung levels of iNOS activity by
      inhibiting expression of iNOS mRNA in animals given ET. APC significantly
      inhibited the increases in lung tissue levels of TNF-alpha and expression of TNF
      alpha mRNA in animals given ET. Neither DEGR-F.Xa, a selective inhibitor of
      thrombin generation, nor DIP-APC, an active site-blocked APC, showed any effect
      on these ET-induced changes. Both inhibition of TNF-alpha production by
      leukocytopenia and treatment with anti-rat TNF-alpha antibody produced effects
      similar to those induced by APC. Aminoguanidine, a selective inhibitor of iNOS,
      inhibited both the hypotension and the increases in plasma levels of NO(2)(
      )/NO(3)(-) in this animal model. CONCLUSIONS: These observations strongly suggest
      that APC inhibits iNOS induction by decreasing TNF-alpha production, leading to
      the prevention of ET-induced hypotension. Furthermore, such effects of APC were
      not dependent on its anticoagulant effects but rather on its serine protease
      activity.

PMID- 11535576
TI  - Increased bleeding tendency and decreased susceptibility to thromboembolism in
      mice lacking the prostaglandin E receptor subtype EP(3).
AB  - BACKGROUND: Among the prostanoids, thromboxane (TX) A(2) is a potent stimulator
      of platelets, whereas prostaglandin (PG) I(2) inhibits their activation. The
      roles of PGE(2) in the regulation of platelet function have not been established,
      however, and the contribution of PGE(2) in hemostasis and thromboembolism is
      poorly understood. The present study was intended to clarify these roles of
      PGE(2) by using mice lacking the PGE(2) receptor subtype 3 (EP(3)(-/-) mice).
      METHODS AND RESULTS: Expression of mRNAs for EP(3) in murine platelets was
      confirmed by quantitative reverse transcription-polymerase chain reaction. PGE(2)
      and AE-248, a selective EP(3) agonist, showed concentration-dependent
      potentiation of platelet aggregation induced by U46619, a TXA(2) receptor
      agonist, although PGE(2) alone could not induce aggregation. PGE(2) and AE-248
      increased cytosolic calcium ion concentration ([Ca(2+)](i)), and AE-248 inhibited
      the forskolin-induced increase in cytosolic cAMP concentration ([cAMP](i)),
      suggesting G(i) coupling of EP(3). The potentiating effects of PGE(2) and AE-248
      on platelet aggregation along with their effects on [Ca(2+)](i) and [cAMP](i)
      were absent in EP(3)(-/-) mice. In vivo, the bleeding time was significantly
      prolonged in EP(3)(-/-) mice. Moreover, when mice were challenged intravenously
      with arachidonic acid, mortality and thrombus formation in the lung were
      significantly reduced in EP(3)(-/-) mice. CONCLUSIONS: - PGE(2) potentiated
      platelet aggregation induced by U46619 via EP(3) by increasing [Ca(2+)](i),
      decreasing [cAMP](i), or both. This potentiating action of PGE(2) via EP(3) is
      essential in mediating both physiological and pathological effects of PGE(2) in
      vivo.

PMID- 11535577
TI  - Pharmacological stress myocardial perfusion imaging with the potent and selective
      A(2A) adenosine receptor agonists ATL193 and ATL146e administered by either
      intravenous infusion or bolus injection.
AB  - BACKGROUND: Adenosine (Ado) and dipyridamole are alternatives to exercise stress
      for myocardial perfusion imaging. Though generally safe, side effects frequently
      occur that cause patient discomfort and sometimes lead to premature termination
      of the study or require aminophylline administration. Recently, a new class of
      A(2A) Ado receptor agonists was synthesized. ATL193 and ATL146e are 2
      propynylcyclohexyl-5'-N-ethylcarboxamido derivatives of Ado. The study goals were
      to evaluate the potency and selectivity of these new compounds on recombinant
      canine Ado receptors and to evaluate their hemodynamic properties in dogs to
      assess their usefulness as vasodilators for myocardial perfusion imaging. METHODS
      AND RESULTS: In assays of recombinant canine Ado receptors, ATL-193 and ATL-146e
      were highly selective for the A(2A) over the A(1) and A(3) receptors and were
      more potent than MRE-0470 and CGS-21680. In 16 anesthetized dogs, the agonists
      were administered by infusion (ATL-193; n=7 normal) or bolus injection (ATL-146e;
      n=9 critical left anterior descending coronary artery stenosis), and hemodynamic
      responses were compared with those of Ado. Both agonists produced dose-dependent
      coronary flow (CF) elevation without provoking the hypotension observed with Ado.
      After an ATL-146e bolus, the CF increase was sustained for several minutes,
      providing ample time for injection and myocardial uptake of (99m)Tc-sestamibi,
      and CF returned to baseline within 20 minutes. The CF increase was completely
      blocked by the selective A(2A) antagonist ZM241385 (3 microgram. kg(-1). min(
      1)). CONCLUSIONS: ATL-193 and ATL-146e are highly potent and selective Ado A(2A)
      receptor agonists with excellent potential for use as vasodilators for myocardial
      perfusion imaging. An important advantage of ATL-146e is the ability to
      administer it by bolus injection.

PMID- 11535578
TI  - Stent-based delivery of sirolimus reduces neointimal formation in a porcine
      coronary model.
AB  - BACKGROUND: The purpose of this study was to determine the efficacy of stent
      based delivery of sirolimus (SRL) alone or in combination with dexamethasone
      (DEX) to reduce in-stent neointimal hyperplasia. SRL is a potent
      immunosuppressive agent that inhibits SMC proliferation by blocking cell cycle
      progression. METHODS AND RESULTS: Stents were coated with a nonerodable polymer
      containing 185 microgram SRL, 350 microgram DEX, or 185 microgram SRL and 350
      microgram DEX. Polymer biocompatibility studies in the porcine and canine models
      showed acceptable tissue response at 60 days. Forty-seven stents (metal, n=13;
      SRL, n=13; DEX, n=13; SRL and DEX, n=8) were implanted in the coronary arteries
      of 16 pigs. The tissue level of SRL was 97+/-13 ng/artery, with a stent content
      of 71+/-10 microgram at 3 days. At 7 days, proliferating cell nuclear antigen and
      retinoblastoma protein expression were reduced 60% and 50%, respectively, by the
      SRL stents. After 28 days, the mean neointimal area was 2.47+/-1.04 mm(2) for the
      SRL alone and 2.42+/-1.04 mm(2) for the combination of SRL and DEX compared with
      the metal (5.06+/-1.88 mm(2), P<0.0001) or DEX-coated stents (4.31+/-3.21 mm(2),
      P<0.001), resulting in a 50% reduction of percent in-stent stenosis. CONCLUSIONS:
      Stent-based delivery of SRL via a nonerodable polymer matrix is feasible and
      effectively reduces in-stent neointimal hyperplasia by inhibiting cellular
      proliferation.

PMID- 11535579
TI  - Heterogeneous expression of Gap junction channels in the heart leads to
      conduction defects and ventricular dysfunction.
AB  - BACKGROUND: - Heterogeneous remodeling of gap junctions is observed in many forms
      of heart disease. The consequent loss of synchronous ventricular activation has
      been hypothesized to result in diminished cardiac performance. To directly test
      this hypothesis, we designed a murine model of heterogeneous gap junction channel
      expression. Methods and Results-- We generated chimeric mice formed from
      connexin43 (Cx43)-deficient embryonic stem cells and wild-type or genetically
      marked ROSA26 recipient blastocysts. Chimeric mice developed normally, without
      histological evidence of myocardial fibrosis or hypertrophy. Heterogeneous Cx43
      expression resulted in conduction defects, however, as well as markedly depressed
      contractile function. Optical mapping of chimeric hearts by use of voltage
      sensitive dyes revealed highly irregular epicardial conduction patterns,
      quantified as significantly greater negative curvature of the activation wave
      front (-1.86+/-0.40 mm in chimeric mice versus -0.86+/-0.098 mm in controls;
      P<0.01; n=6 for each group). Echocardiographic studies demonstrated significantly
      reduced fractional shortening in chimeric mice (26.6+/-2.3% versus 36.5+/-1.6% in
      age-matched 129/SvxC57BL/6F1 wild-type controls; P<0.05). CONCLUSIONS: - These
      data suggest that heterogeneous Cx43 expression, by perturbing the normal pattern
      of coordinated myocardial excitation, may directly depress cardiac performance.

PMID- 11535580
TI  - Gating-dependent mechanisms for flecainide action in SCN5A-linked arrhythmia
      syndromes.
AB  - BACKGROUND: Mutations in the cardiac sodium (Na) channel gene (SCN5A) give rise
      to the congenital long-QT syndrome (LQT3) and the Brugada syndrome. Na channel
      blockade by antiarrhythmic drugs improves the QT interval prolongation in LQT3
      but worsens the Brugada syndrome ST-segment elevation. Although Na channel
      blockade has been proposed as a treatment for LQT3, flecainide also evokes
      "Brugada-like" ST-segment elevation in LQT3 patients. Here, we examine how Na
      channel inactivation gating defects in LQT3 and Brugada syndrome elicit
      proarrhythmic sensitivity to flecainide. METHODS AND RESULTS: We measured whole
      cell Na current (I(Na)) from tsA-201 cells transfected with DeltaKPQ, a LQT3
      mutation, and 1795insD, a mutation that provokes both the LQT3 and Brugada
      syndromes. The 1795insD and DeltaKPQ channels both exhibited modified
      inactivation gating (from the closed state), thus potentiating tonic I(Na) block.
      Flecainide (1 micromol/L) tonic block was only 16.8+/-3.0% for wild type but was
      58.0+/-6.0% for 1795insD (P<0.01) and 39.4+/-8.0% (P<0.05) for DeltaKPQ. In
      addition, the 1795insD mutation delayed recovery from inactivation by enhancing
      intermediate inactivation, with a 4-fold delay in recovery from use-dependent
      flecainide block. CONCLUSIONS: We have linked 2 inactivation gating defects
      ("closed-state" fast inactivation and intermediate inactivation) to flecainide
      sensitivity in patients carrying LQT3 and Brugada syndrome mutations. These
      results provide a mechanistic rationale for predicting proarrhythmic sensitivity
      to flecainide based on the identification of specific SCN5A inactivation gating
      defects.

PMID- 11535581
TI  - Identification of fetal atrial flutter by Doppler tissue imaging.

PMID- 11535582
TI  - Less is more: 4:2:1 block.

PMID- 11535583
TI  - Sphingosylphosphorylcholine and lysophosphatidylcholine are ligands for the G
      protein-coupled receptor GPR4.
AB  - Sphingosylphosphorylcholine (SPC) and lysophosphatidylcholine (LPC) are bioactive
      lipid molecules involved in numerous biological processes. We have recently
      identified ovarian cancer G protein-coupled receptor 1 (OGR1) as a specific and
      high affinity receptor for SPC, and G2A as a receptor with high affinity for LPC,
      but low affinity for SPC. Among G protein-coupled receptors, GPR4 shares highest
      sequence homology with OGR1 (51%). In this work, we have identified GPR4 as not
      only another high affinity receptor for SPC, but also a receptor for LPC, albeit
      of lower affinity. Both SPC and LPC induce increases in intracellular calcium
      concentration in GPR4-, but not vector-transfected MCF10A cells. These effects
      are insensitive to treatment with BN52021, WEB-2170, and WEB-2086 (specific
      platelet activating factor (PAF) receptor antagonists), suggesting that they are
      not mediated through an endogenous PAF receptor. SPC and LPC bind to GPR4 in GPR4
      transfected CHO cells with K(d)/SPC = 36 nm, and K(d)/LPC = 159 nm, respectively.
      Competitive binding is elicited only by SPC and LPC. Both SPC and LPC activate
      GPR4-dependent activation of serum response element reporter and receptor
      internalization. Swiss 3T3 cells expressing GPR4 respond to both SPC and LPC, but
      not sphingosine 1-phosphate (S1P), PAF, psychosine (Psy), glucosyl-beta1'1
      sphingosine (Glu-Sph), galactosyl-beta1'1-ceramide (Gal-Cer), or lactosyl-beta1'1
      ceramide (Lac-Cer) to activate extracellular signal-regulated kinase mitogen
      activated protein kinase in a concentration- and time-dependent manner. SPC and
      LPC stimulate DNA synthesis in GPR4-expressing Swiss 3T3 cells. Both
      extracellular signal-regulated kinase activation and DNA synthesis stimulated by
      SPC and LPC are pertussis toxin-sensitive, suggesting the involvement of a G(i)
      heterotrimeric G protein. In addition, GPR4 expression confers chemotactic
      responses to both SPC and LPC in Swiss 3T3 cells. Taken together, our data
      indicate that GPR4 is a receptor with high affinity to SPC and low affinity to
      LPC, and that multiple cellular functions can be transduced via this receptor.

PMID- 11535584
TI  - Glial cell line-derived neurotrophic factor-stimulated phosphatidylinositol 3
      kinase and Akt activities exert opposing effects on the ERK pathway: importance
      for the rescue of neuroectodermic cells.
AB  - Glial cell line-derived neurotrophic factor (GDNF) plays a crucial role in
      rescuing neural crest cells from apoptosis during their migration in the foregut.
      This survival factor binds to the heterodimer GDNF family receptor alpha1/Ret,
      inducing the Ret tyrosine kinase activity. ret loss-of-function mutations result
      in Hirschsprung's disease, a frequent developmental defect of the enteric nervous
      system. Although critical to enteric nervous system development, the
      intracellular signaling cascades activated by GDNF and their importance in
      neuroectodermic cell survival still remain elusive. Using the neuroectodermic SK
      N-MC cell line, we found that the Ret tyrosine kinase activity is essential for
      GDNF to induce phosphatidylinositol 3-kinase (PI3K)/Akt and ERK pathways as well
      as cell rescue. We demonstrate that activation of PI3K is mandatory for GDNF
      induced cell survival. In addition, evidence is provided for a critical up
      regulation of the ERK pathway by PI3K at the level of Raf-1. Conversely, Akt
      inhibits the ERK pathway. Thus, both PI3K and Akt act in concert to finely
      regulate the level of ERK. We found that Akt activation is indispensable for
      counteracting the apoptotic signal on mitochondria, whereas ERK is partially
      involved in precluding procaspase-3 cleavage. Altogether, these findings
      underscore the importance of the Ret/PI3K/Akt pathway in GDNF-induced
      neuroectodermic cell survival.

PMID- 11535585
TI  - Enhancement of epidermal growth factor signaling and activation of SRC kinase by
      gangliosides.
AB  - In a recent study, inhibition of cellular ganglioside synthesis blocked growth
      factor-induced fibroblast proliferation. Conversely, enrichment of cell membrane
      gangliosides by ganglioside preincubation enhanced growth factor-elicited cell
      proliferation. In the absence of serum and growth factors, NeuNAcalpha2-3Galbeta1
      3GalNAcbeta1-4(NeuNAcalpha2-3)Galbeta1-4Glcbeta1-1Cer (G(D1a)) acted like a
      growth factor when cells were pretreated with the ganglioside, stimulating
      proliferation of normal human dermal fibroblasts and Swiss 3T3 fibroblasts. In
      contrast, growth inhibition was observed when high concentrations of gangliosides
      were continuously present in the culture medium during incubation of fibroblasts
      with growth factors (Li, R., Manela, J., Kong, Y., and Ladisch, S. (2000) J.
      Biol. Chem. 275, 34213-34223). Here, we investigated the mechanisms whereby
      gangliosides elicit proliferation-coupled signaling in normal human dermal
      fibroblasts. Incubation of the fibroblasts with G(D1a) enhanced epidermal growth
      factor (EGF) receptor autophosphorylation and Ras and MAPK activation in a dose
      dependent manner. Exposure of the cells to G(D1a) also enhanced the
      phosphorylation of Elk-1 by the activated MAPK. Brief pretreatment of the cells
      with PD98059 blocked the enhancing effect of gangliosides on EGF-induced MAPK
      activation. In the absence of serum and growth factors, G(D1a) incubation induced
      phosphorylation of Src kinase, Ras activation, and phosphorylation of MAPK and
      Elk-1 in a dose-dependent manner. The activation of Src kinase was confirmed by
      enhanced Src kinase activity. Brief treatment of the cells with PP1 blocked the
      activation of Src kinase and MAPK. Again, PD98059 treatment inhibited ganglioside
      elicited MAPK phosphorylation. Among the gangliosides tested, G(D1a), was the
      most active molecule, whereas lactosylceramide was the least active one,
      indicating relative structural specificity of the ganglioside action. In
      conclusion, gangliosides promote fibroblast proliferation through enhancement of
      growth factor signaling and activation of Src kinase.

PMID- 11535586
TI  - The C-terminal nuclear localization signal of the sex-determining region Y (SRY)
      high mobility group domain mediates nuclear import through importin beta 1.
AB  - The sex-determining factor SRY is a DNA-binding protein that diverts primordial
      gonads from the ovarian pathway toward male differentiation to form testes. It
      gains access to the nucleus through two distinct nuclear localization signals
      (NLSs) that flank the high mobility group (HMG) DNA-binding domain, but the
      mechanisms through which these NLSs operate have not been studied. In this study,
      we reconstitute the nuclear import of SRY in vitro, demonstrating a lack of
      requirement for exogenous factors for nuclear accumulation and a significant
      reduction in nuclear transport in the presence of antibodies to importin beta but
      not importin alpha. Using a range of quantitative binding assays including enzyme
      linked immunosorbent assay, fluorescence polarization, and native gel mobility
      electrophoresis, we assess the binding of importins to SRY, demonstrating a high
      affinity recognition (in the low nm range) by Imp beta independent of Imp alpha.
      In assessing the contribution of each NLS, we found that the N-terminal NLS was
      recognized poorly by importins, whereas the C-terminal NLS was bound by importin
      beta with similar affinity to SRY. We also found that RanGTP, but not RanGDP,
      could dissociate the SRY-importin beta complex in solution using FP. We describe
      a novel double-fluorescent label DNA binding assay to demonstrate mutual
      exclusivity between importin beta recognition and DNA binding on the part of SRY,
      which may represent an alternative release mechanism upon nuclear entry. This
      study represents the first characterization of the nuclear import pathway for a
      HMG domain-containing protein. Importantly, it demonstrates for the first time
      that recognition of SRY by Imp beta is of comparable affinity to that with which
      Imp alpha/beta recognizes conventional NLS-containing substrates.

PMID- 11535587
TI  - Cytosolic targeting domains of gamma and delta calmodulin-dependent protein
      kinase II.
AB  - Ca(2+)/calmodulin-dependent protein kinase II (CaMK-II) isozyme variability is
      the result of alternative usage of variable domain sequences. Isozyme expression
      is cell type-specific to transduce the appropriate Ca(2+) signals. We have
      determined the subcellular targeting domain of delta(E) CaMK-II, an isozyme that
      induces neurite outgrowth, and of a structurally similar isozyme, gamma(C) CaMK
      II, which does not induce neurite outgrowth. delta(E) CaMK-II co-localizes with
      filamentous actin in the perinuclear region and in cellular extensions. In
      contrast, gamma(C) CaMK-II is uniformly cytosolic. Constitutively active delta(E)
      CaMK-II induces F-actin-rich extensions, thereby supporting a functional role for
      its localization. C-terminal constructs, which lack central variable domain
      sequences, can oligomerize and localize like full-length delta(E) and gamma(C)
      CaMK-II. Central variable domains themselves are monomeric and have no targeting
      capability. The C-terminal 95 residues of delta CaMK-II also has no targeting
      capability but can efficiently oligomerize. These findings define a targeting
      domain for gamma and delta CaMK-IIs that is in between the central variable and
      association domains. This domain is responsible for the subcellular targeting
      differences between gamma and delta CaMK-IIs.

PMID- 11535588
TI  - Proteome analysis and morphological studies reveal multiple effects of the
      immunosuppressive drug mycophenolic acid specifically resulting from guanylic
      nucleotide depletion.
AB  - Mycophenolic acid (MPA), one of the most promising immunosuppressive drugs
      recently developed, is a potent inhibitor of IMP dehydrogenase, the first
      committed step toward GMP synthesis. We found that all the drug effects on yeast
      cells were prevented by bypassing GMP synthesis, thus confirming the high
      specificity of MPA. Although the primary target of MPA is clearly identified, we
      aimed to further understand how GTP depletion leads to growth arrest and
      developed a new approach based on proteome analysis combined with overexpression
      studies. Essential proteins down-expressed in the presence of MPA were identified
      by protein two-dimensional gel analysis and subsequently overexpressed in yeast.
      Two such proteins, Cdc37p and Sup45p, when overexpressed allowed partial relief
      of MPA toxicity, strongly suggesting that their lower amount after MPA treatment
      significantly contributed to the MPA effect. These conserved proteins involved in
      cell cycle progression and translation are therefore important secondary targets
      for MPA. Our data establish that MPA effects occur through inhibition of a unique
      primary target resulting in guanine nucleotides depletion, thereby affecting
      multiple cellular processes.

PMID- 11535589
TI  - Membrane topography and topogenesis of prenylated Rab acceptor (PRA1).
AB  - The mouse prenylated Rab acceptor (mPRA1) is associated with the Golgi membrane
      at steady state and interacts with Rab proteins. It contains two internal
      hydrophobic domains (34 residues each) that have enough residues to form four
      transmembrane (TM) segments. In this study, we have determined the membrane
      topography of mPRA1 in both intact cells and isolated microsomes. The putative TM
      segments of mPRA1 were used to substitute for a known TM segment of a model
      membrane protein to determine whether the mPRA1 segments integrate into the
      membrane. Furthermore, N-linked glycosylation scanning methods were used to
      distinguish luminal domains from cytoplasmic domains of mPRA1. The data
      demonstrate that mPRA1 is a polytopic membrane protein containing four TM
      segments. These TM segments act cooperatively during the translocation and
      integration at the endoplasmic reticulum membrane. All hydrophilic domains are in
      the cytoplasm, including the N-terminal domain, the linker domain between the two
      hydrophobic domains, and the C-terminal domain. As a result, the bulk of mPRA1 is
      located in the cytoplasm, supporting its postulated role in regulating Rab
      membrane targeting and intracellular trafficking.

PMID- 11535590
TI  - Expression and secretion of a larval-specific chitinase (family 18 glycosyl
      hydrolase) by the infective stages of the parasitic nematode, Onchocerca
      volvulus.
AB  - A recently reported chitinase gene, expressed in the infective, third-stage (L3)
      larvae of the human filarial parasite Onchocerca volvulus, belongs to the family
      18 glycosyl hydrolases and has been designated Ov-chi-1. The gene product of Ov
      chi-1 is chitinolytic. Allosamidin ablates activity of the native enzyme in a
      dose-dependent manner but did not significantly inhibit the moulting of L3
      larvae. Mono-specific antibodies were used to characterize Ov-CHI-1 as a 60-kDa
      protein expressed almost exclusively in L3 stages. Immunoelectron microscopy
      showed that Ov-CHI-1 expression is initiated in late L2 larvae and increases
      markedly in infective, L3 larvae. It is synthesized exclusively in the glandular
      esophagus and stored within discrete secretory granules. Secretion occurs through
      de-granulation during post-infective development, and the primary route of
      transport appears to be via the pseudo-coelom. An orthologue of Ov-chi-1 was
      detected in Caenorhabditis elegans by BLAST analysis. It is constitutively
      expressed at a low level and is overexpressed in dauer larvae and embryonated
      eggs. It is chitinolytic. We conclude that Ov-CHI-1 is a highly stage-specific
      enzyme that may have a role in infectivity of the parasite, aiding escape from
      the vector or participating in early post-infective migration and/or development.
      The identification of an orthologue in C. elegans opens the way for further
      studies into the biological function(s) of this intriguing parasite product.

PMID- 11535591
TI  - Oligomerization of the human thyrotropin receptor: fluorescent protein-tagged
      hTSHR reveals post-translational complexes.
AB  - To examine thyrotropin (TSH) receptor homophilic interactions we fused the human
      TSH receptor (hTSHR) carboxyl terminus to green fluorescent protein (GFP) and the
      corresponding chimeric cDNA was expressed in Chinese hamster ovary cells.
      Fluorescent TSH receptors on the plasma membrane were functional as assessed by
      TSH-induced cAMP synthesis. The binding of TSH, as well as TSHR autoantibodies,
      induced time- and dose-dependent receptor capping. Fluorescence resonance energy
      transfer between receptors differentially tagged with GFP variants (RFP and YFP)
      provided evidence for the close proximity of individual receptor molecules. This
      was consistent with previous studies demonstrating the presence of TSHR dimers
      and oligomers in thyroid tissue. Co-immunoprecipitation of GFP-tagged and Myc
      tagged receptor complexes was performed using doubly transfected cells with Myc
      antibody. Western blotting of the immunoprecipitated complex revealed the absence
      of noncleaved TSH holoreceptors. This further suggested that cleavage of the
      holoreceptor into its two-subunit structure, comprising disulfide-linked TSHR
      alpha and TSHR-beta subunits, was required for the formation of TSHR dimers and
      higher order complexes.

PMID- 11535592
TI  - The nonreceptor tyrosine kinase ACK2, a specific target for Cdc42 and a negative
      regulator of cell growth and focal adhesion complexes.
AB  - ACK2 (activated Cdc42-associated tyrosine kinase-2) is a nonreceptor tyrosine
      kinase that is a specific target/effector for the GTP-binding protein Cdc42. Thus
      far the biological function of this tyrosine kinase has not been determined.
      Using an inducible eukaryotic expression system in fibroblasts, we demonstrate
      that ACK2 can strongly influence cell shape and growth as well as focal complex
      formation. ACK2 was found to associate with the focal adhesion complex components
      talin and vinculin, but not with the focal adhesion kinase (FAK), in a kinase
      independent manner. The tyrosine kinase activity of FAK was also inhibited in
      cells overexpressing both wild-type and kinase-defective ACK2. This may be due to
      a competition between ACK2 and FAK for Src, which is an essential cofactor for
      FAK activation, as we have found that ACK2 specifically binds Src in cells. The
      ACK2-Src interaction appears to be mediated by the SH3 domain of Src, and the
      phosphorylation of ACK2 is enhanced in cells overexpressing the hyperactivated
      Src(Y527F) mutant. Overexpression of both wild-type and kinase-defective ACK2
      also results in a severe inhibition of cell growth. In addition, ACK2 dissolves
      actin stress fibers and disassembles focal complexes but in a kinase-dependent
      manner. These results, taken together with previous studies demonstrating an
      association of ACK2 with integrin beta(1) (Yang, W., Lin, Q., Guan, J.-L.,
      Cerione, R. A. (1999) J. Biol. Chem. 274, 8524-8530) and clathrin (Yang, W., Lo,
      C. G., Dispenza, T., and Cerione, R. A. (2001) J. Biol. Chem. 276, 17468-17473),
      suggest that the binding and protein tyrosine kinase activities of ACK2
      coordinate changes in cell morphology and growth with the disassembly of focal
      adhesion sites, perhaps to organize new integrin complexes that are required for
      endocytosis and/or for cellular differentiation.

PMID- 11535593
TI  - Amino acids in the cytoplasmic C terminus of the parathyroid Ca2+-sensing
      receptor mediate efficient cell-surface expression and phospholipase C
      activation.
AB  - The C-terminal tail of the calcium receptor (CaR) regulates the affinity of the
      receptor for ligand, desensitization, and membrane localization. To determine the
      role of specific amino acids in the bovine parathyroid CaR in mediating signal
      transduction and cell-surface expression, we transfected truncated and mutated
      CaR cDNAs into HEK-293 cells. The ability of high extracellular [Ca(2+)]
      ([Ca(2+)](o)) to increase total inositol phosphate (InsP) production, an index of
      phospholipase C (PLC) activation, was determined. Receptor expression was
      assessed by immunoblotting and immunocytochemistry. In cells transiently or
      stably expressing receptors with the C-terminal tail truncated after residue 895
      (CaR-(1-895)) or 929 (CaR-(1-929)), raising [Ca(2+)](o) increased InsPs to levels
      comparable with those of cells expressing wild-type CaRs. There were no PLC
      responses to high [Ca(2+)](o) (up to 30 mm) in cells expressing CaRs with C
      terminal tails of only 3 residues (CaR-(1-866)), even though these receptors were
      expressed in the membrane. We scanned the residues between Ser(866) and Val(895)
      using tandem-Ala and single-site mutagenesis. Two point mutants (His(880) --> Ala
      and Phe(882) --> Ala CaR) showed 50-70% reductions in high [Ca(2+)](o)-induced
      InsP production. The levels of expression and glycosylation of these mutants were
      comparable with wild-type CaRs, but both receptors were profoundly retained in
      intracellular organelles and co-localized with the endoplasmic reticulum marker
      BiP. This suggested that the signaling defects of these receptors were likely
      because of defective trafficking of receptors to the cell surface. Modeling of
      the C-terminal domain of the CaR indicated that His(880) and Phe(882) are
      situated in a putative alpha-helical structure of 15 amino acids between residues
      877 and 891 in the C-terminal tail. Our studies support the idea that specific
      amino acids, and possibly a unique secondary structure in the C-terminal tail,
      are required for the efficient targeting of the CaR to the cell surface required
      for PLC activation.

PMID- 11535594
TI  - Transcriptional regulation of the human sterol 12alpha-hydroxylase gene (CYP8B1):
      roles of heaptocyte nuclear factor 4alpha in mediating bile acid repression.
AB  - Sterol 12alpha-hydroxylase catalyzes the synthesis of cholic acid and controls
      the ratio of cholic acid over chenodeoxycholic acid in the bile. Transcription of
      CYP8B1 is inhibited by bile acids, cholesterol, and insulin. To study the
      mechanism of CYP8B1 transcription by bile acids, we have cloned and determined
      3389 base pairs of the 5'-upstream nucleotide sequences of the human CYP8B1.
      Deletion analysis of CYP8B1/luciferase reporter activity in HepG2 cells revealed
      that the sequences from -57 to +300 were important for basal and liver-specific
      promoter activities. Hepatocyte nuclear factor 4alpha (HNF4alpha) strongly
      activated human CYP8B1 promoter activities, whereas cholesterol 7alpha
      hydroxylase promoter factor (CPF), an NR5A2 family of nuclear receptors, had much
      less effect. Electrophoretic mobility shift assay identified an overlapping
      HNF4alpha- and CPF-binding site in the +198/+227 region. The human CYP8B1
      promoter activities were strongly repressed by bile acids, and the bile acid
      response element was localized between +137 and +220. Site-directed mutagenesis
      of the HNF4alpha-binding site markedly reduced promoter activity and its response
      to bile acid repression. On the other hand, mutation of the CPF-binding site had
      little effect on promoter activity and bile acid inhibition. A negative nuclear
      receptor, small heterodimer partner markedly inhibited transactivation of CYP8B1
      by HNF4alpha. Mammalian two-hybrid assay confirmed that HNF4alpha interacted with
      small heterodimer partner. Furthermore, bile acids and farnesoid X receptor
      reduced the expression of nuclear HNF4alpha in HepG2 cells and rat livers and its
      binding to DNA. Bile acids and farnesoid X receptor also inhibited mouse
      HNF4alpha gene transcription. In summary, our data revealed the critical roles
      HNF4alpha play on CYP8B1 transcription and its repression by bile acids. Bile
      acids repress human CYP8B1 transcription by reducing the transactivation activity
      of HNF4alpha through interaction of HNF4alpha with SHP and reduction of HNF4alpha
      expression in the liver.

PMID- 11535595
TI  - Inhibition of protein translocation across the endoplasmic reticulum membrane by
      sterols.
AB  - Cholesterol and related sterols are known to modulate the physical properties of
      biological membranes and can affect the activities of membrane-bound protein
      complexes. Here, we report that an early step in protein translocation across the
      endoplasmic reticulum (ER) membrane is reversibly inhibited by cholesterol levels
      significantly lower than those found in the plasma membrane. By UV-induced
      chemical cross-linking we further show that high cholesterol levels prevent cross
      linking between ribosome-nascent chain complexes and components of the Sec61
      translocon, but have no effect on cross-linking to the signal recognition
      particle. The inhibiting effect on translocation is different between different
      sterols. Our data suggest that the protein translocation machinery may be
      sensitive to changes in cholesterol levels in the ER membrane.

PMID- 11535596
TI  - Calcium-regulated DNA binding and oligomerization of the neuronal calcium-sensing
      protein, calsenilin/DREAM/KChIP3.
AB  - Calsenilin/DREAM/KChIP3, a member of the recoverin branch of the EF-hand
      superfamily, interacts with presenilins, serves as a calcium-regulated
      transcriptional repressor, and interacts with A-type potassium channels. Here we
      report physicochemical characterization of calcium binding, oligomerization, and
      DNA binding of human calsenilin/DREAM/KChIP3. Equilibrium Ca(2+) binding
      measurements indicate that the protein binds 3 Ca(2+) with a dissociation
      constant of 14 microM and a Hill coefficient of 0.7. Dynamic light scattering and
      size exclusion chromatography show that the Ca(2+)-bound protein exists as a
      dimer at protein concentrations lower than 150 microM and forms a tetramer at
      concentrations above 200 microM. The Ca(2+)-free protein is a tetramer in the
      concentration range 20-450 microM. Isothermal titration calorimetry and dynamic
      light scattering indicate that the Ca(2+)-free protein tetramer binds
      endothermically (DeltaH = +25 kcal/mol) to four molecules of DNA derived from the
      downstream regulatory element (DRE) of either the prodynorphin or c-fos genes.
      One DRE molecule binds tightly to the protein with a dissociation constant (K(d))
      of 75 nM, and the other three bind more weakly (K(d) = 640 nM). No significant
      DNA binding was observed for the Ca(2+)-bound protein. The N-terminal protein
      fragment (residues 1-70) binds nonspecifically to DRE in a Ca(2+)-independent
      manner, whereas a C-terminal fragment containing the four EF-hands (residues 65
      256) binds DRE (K(d) = 200 nM) in a Ca(2+)-regulated and sequence-specific
      fashion. The C-terminal fragment is a tetramer in the Ca(2+)-free state and
      dissociates into dimers at saturating Ca(2+) levels.

PMID- 11535597
TI  - Measles virus envelope glycoproteins hetero-oligomerize in the endoplasmic
      reticulum.
AB  - The endoplasmic reticulum (ER) was investigated as the initial oligomerization
      site for the envelope glycoproteins H and F of measles virus (MV), a clinically
      relevant member of the Paramyxoviridae family, and consequences of this
      interaction for viral replication were studied. Both proteins were tagged at
      their cytosolic tails with RRR and KKXX motifs, respectively, resulting in their
      efficient retention in the ER. Co-transfection of the retained constructs with
      transport competent MV glycoproteins revealed a dominant negative effect on their
      biological activity indicating intracellular complex formation and thus
      retention. Pulse-chase analysis and co-immunoprecipitation experiments
      demonstrated that this effect is based on both homo- and hetero-oligomerization
      in the ER. Recombinant viruses additionally expressing ER-retained F showed an
      altered cytopathic phenotype accompanied by greatly reduced particle release.
      Similar mutant viruses additionally expressing ER-retained H could not be rescued
      indicating an even greater negative effect of this protein on virus viability.
      Our study suggests that both homo- and hetero-oligomerization of MV glycoproteins
      occur in the ER and that these events are of significance for early steps of
      particle assembly.

PMID- 11535598
TI  - Essential role for NHERF in cAMP-mediated inhibition of the Na+-HCO3- co
      transporter in BSC-1 cells.
AB  - Prior studies have indicated a requirement for the PDZ domain-containing protein,
      Na(+)/H(+) Exchanger Regulatory Factor (NHERF), for protein kinase A (PKA)
      mediated inhibition of the renal basolateral Na(+)-HCO(3)(-) co-transporter
      (NBC). The present studies explore the potential mechanisms by which NHERF
      transduces cAMP signals to inhibit NBC. In BSC-1 cells, cells that express NBC
      but lack NHERF, 8-bromo-cAMP (100 microm for 15 min) failed to inhibit transport
      until wild-type mNHERF-(1-355) was expressed. mNHERF-(116-355) containing PDZ II
      and C-terminal ezrin-binding sequences or a mutant unphosphorylated form of
      rabbit NHERF effectively transduced the cAMP signals that inhibited NBC. By
      contrast, mNHERF-(1-126) encompassing N-terminal PDZ I and mNHERF-(1-325), which
      lacks ezrin-binding, failed to support cAMP inhibition of NBC activity. NBC and
      NHERF did not associate with each other in yeast two-hybrid or co
      immunoprecipitation assays, and confocal microscopy indicated distinct
      subcellular localization of the two proteins. NBC was phosphorylated in BSC-1
      cells, but its phosphorylation was not increased by cAMP nor was
      immunoprecipitated NBC phosphorylated by PKA in vitro. Acute exposure of mNHERF
      (1-355)-expressing BSC-1 cells to cAMP did not change cell surface expression of
      NBC. Although these results established an essential role for NHERF in cAMP
      mediated inhibition of NBC in BSC-1 cells, they also suggest a novel mechanism
      for NHERF-mediated signal transduction distinct from that previously
      characterized from studies of other NHERF targets.

PMID- 11535599
TI  - The roles of phosphatidylinositol 3-kinase and protein kinase Czeta for
      thrombopoietin-induced mitogen-activated protein kinase activation in primary
      murine megakaryocytes.
AB  - Thrombopoietin (TPO) stimulates a network of intracellular signaling pathways
      that displays extensive cross-talk. We have demonstrated previously that the
      ERK/mitogen-activated protein kinase pathway is important for TPO-induced
      endomitosis in primary megakaryocytes (MKs). One known pathway by which TPO
      induces ERK activation is through the association of Shc with the penultimate
      phosphotyrosine within the TPO receptor, Mpl. However, several investigators
      found that the membrane-proximal half of the cytoplasmic domain of Mpl is
      sufficient to activate ERK in vitro and support base-line megakaryopoiesis in
      vivo. Using BaF3 cells expressing a truncated Mpl (T69Mpl) as a tool to identify
      non-Shc/Ras-dependent signaling pathways, we describe here novel mechanisms of
      TPO-induced ERK activation mediated, in part, by phosphoinositide 3-kinase
      (PI3K). Similar to cells expressing full-length receptor, PI3K was activated by
      its incorporation into a complex with IRS2 or Gab2. Furthermore, the MEK
      phosphorylating activity of protein kinase Czeta (PKCzeta) was also enhanced
      after TPO stimulation of T69Mpl, contributing to ERK activity. PKCzeta and PI3K
      also contribute to TPO-induced ERK activation in MKs, confirming their
      physiological relevance. Like in BaF3 cells, a TPO-induced signaling complex
      containing p85PI3K is detectable in MKs expressing T61Mpl and is probably
      responsible for PI3K activation. These data demonstrate a novel role of PI3K and
      PKCzeta in steady-state megakaryopoiesis.

PMID- 11535600
TI  - Functional analyses of two alternative isoforms of the transcription factor Pax
      5.
AB  - The Pax-5 gene plays a central role in B cell development, activation, and
      differentiation. At least four different isoforms have been identified, of which
      isoform Pax-5a has been extensively studied, while functions for alternative
      isoforms were previously unknown. Here, using a transient transfection system, we
      provide evidence that alternative isoform Pax-5d acts as a dominant-negative
      regulator by suppressing activity of Pax-5a in a dose-dependent manner. In
      contrast, co-expression in the presence of alternative isoform Pax-5e causes an
      increase in Pax-5a activity. Protein studies on Pax-5e using Western blot
      analysis revealed that this 19-kDa isoform migrates as a 27-kDa species on SDS
      polyacrylamide electrophoresis gels, while a mutant Pax-5e form in which a C
      terminal cysteine residue has been mutated, runs at the expected 19 kDa. Using
      both Western blot and immunoprecipitation assays, we further provide evidence
      that this size discrepancy may be caused by a tight association between Pax-5e
      and a thioredoxin-like factor. Comparison of various B cell lines as well as
      resting and lipopolysaccharide-activated mature B lymphocytes shows that
      increased B cell proliferation correlates with increased levels of Pax
      5e/thioredoxin, whereas increased Pax-5d amounts correlate with inhibition of
      cell growth. Together, our results suggest that during activation and
      differentiation of B lymphocytes, Pax-5a function is modulated by two alternative
      spliced isoforms: the dominant negative Pax-5d isoform may mediate inhibition of
      Pax-5a activity in resting B cells, while alternative isoform Pax-5e associated
      with thioredoxin may increase Pax-5a activity through an unknown (redox)
      mechanism.

PMID- 11535601
TI  - Prefoldin recognition motifs in the nonhomologous proteins of the actin and
      tubulin families.
AB  - Nascent actin and tubulin molecules undergo a series of complex interactions with
      chaperones and are thereby guided to their native conformation. These
      cytoskeletal proteins have the initial part of the pathway in common: both
      interact with prefoldin and with the cytosolic chaperonin containing tailless
      complex polypeptide 1. Little is understood with regard to how these chaperones
      and, in particular, prefoldin recognize the non-native forms of these target
      proteins. Using mutagenesis, we provide evidence that beta-actin and alpha
      tubulin each have two prefoldin interaction sites. The most amino-terminally
      located site of both proteins shows striking sequence similarity, although these
      proteins are nonhomologous. Very similar motifs are present in beta- and gamma
      tubulin and in the newly identified prefoldin target protein actin-related
      protein 1. Actin-related proteins 2 and 3 have related motifs, but these have
      altered charge properties. The latter two proteins do not bind prefoldin,
      although we identify them here as target proteins for the cytosolic chaperonin.
      Actin fragments containing the two prefoldin interaction regions compete
      efficiently with actin for prefoldin binding. In addition, they also compete with
      tubulins, suggesting that these target proteins contact similar prefoldin
      subunits.

PMID- 11535602
TI  - Structures of yeast ARF2 and ARL1: distinct roles for the N terminus in the
      structure and function of ARF family GTPases.
AB  - Structures were determined by x-ray crystallography for two members of the ADP
      ribosylation factor (ARF) family of regulatory GTPases, yeast ARF1 and ARL1, and
      were compared with previously determined structures of human ARF1 and ARF6. These
      analyses revealed an overall conserved fold but differences in primary sequence
      and length, particularly in an N-terminal loop, lead to differences in nucleotide
      and divalent metal binding. Packing of hydrophobic residues is central to the
      interplay between the N-terminal alpha-helix, switch I, and the interswitch
      region, which along with differences in surface electrostatics provide
      explanations for the different biophysical and biochemical properties of ARF and
      ARF-like proteins.

PMID- 11535603
TI  - Lipid A modifications in polymyxin-resistant Salmonella typhimurium: PMRA
      dependent 4-amino-4-deoxy-L-arabinose, and phosphoethanolamine incorporation.
AB  - Lipid A of Salmonella typhimurium can be resolved into multiple molecular
      species. Many of these substances are more polar than the predominant hexa
      acylated lipid A 1,4'-bisphosphate of Escherichia coli K-12. By using new
      isolation methods, we have purified six lipid A subtypes (St1 to St6) from wild
      type S. typhimurium. We demonstrate that these lipid A variants are covalently
      modified with one or two 4-amino-4-deoxy-l-arabinose (l-Ara4N) moieties. Each
      lipid A species with a defined set of polar modifications can be further
      derivatized with a palmitoyl moiety and/or a 2-hydroxymyristoyl residue in place
      of the secondary myristoyl chain at position 3'. The unexpected finding that St5
      and St6 contain two l-Ara4N residues accounts for the anomalous structures of
      lipid A precursors seen in S. typhimurium mutants defective in 3-deoxy-d-manno
      octulosonic acid biosynthesis in which only the 1-phosphate group is modified
      with the l-Ara4N moiety (Strain, S. M., Armitage, I. M., Anderson, L., Takayama,
      K., Quershi, N., and Raetz, C. R. H. (1985) J. Biol. Chem. 260, 16089-16098).
      Phosphoethanolamine (pEtN)-modified lipid A species are much less abundant than l
      Ara4N containing forms in wild type S. typhimurium grown in broth but accumulate
      to high levels when l-Ara4N synthesis is blocked in pmrA(C)pmrE(-) and
      pmrA(C)pmrF(-) mutants. Purification and analysis of selected compounds
      demonstrate that one or two pEtN moieties may be present. Our findings show that
      S. typhimurium contains versatile enzymes capable of modifying both the 1- and 4'
      phosphates of lipid A with l-Ara4N and/or pEtN groups. PmrA null mutants of S.
      typhimurium produce lipid A species without any pEtN or l-Ara4N substituents.
      However, PmrA is not needed for the incorporation of 2-hydroxymyristate or
      palmitate.

PMID- 11535604
TI  - An inner membrane enzyme in Salmonella and Escherichia coli that transfers 4
      amino-4-deoxy-L-arabinose to lipid A: induction on polymyxin-resistant mutants
      and role of a novel lipid-linked donor.
AB  - Attachment of the cationic sugar 4-amino-4-deoxy-l-arabinose (l-Ara4N) to lipid A
      is required for the maintenance of polymyxin resistance in Escherichia coli and
      Salmonella typhimurium. The enzymes that synthesize l-Ara4N and transfer it to
      lipid A have not been identified. We now report an inner membrane enzyme,
      expressed in polymyxin-resistant mutants, that adds one or two l-Ara4N moieties
      to lipid A or its immediate precursors. No soluble factors are required. A gene
      located near minute 51 on the S. typhimurium and E. coli chromosomes (previously
      termed orf5, pmrK, or yfbI) encodes the l-Ara4N transferase. The enzyme, renamed
      ArnT, consists of 548 amino acid residues in S. typhimurium with 12 possible
      membrane-spanning regions. ArnT displays distant similarity to yeast protein
      mannosyltransferases. ArnT adds two l-Ara4N units to lipid A precursors
      containing a Kdo disaccharide. However, as shown by mass spectrometry and NMR
      spectroscopy, it transfers only a single l-Ara4N residue to the 1-phosphate
      moiety of lipid IV(A), a precursor lacking Kdo. Proteins with full-length
      sequence similarity to ArnT are present in genomes of other bacteria thought to
      synthesize l-Ara4N-modified lipid A, including Pseudomonas aeruginosa and
      Yersinia pestis. As shown in the following article (Trent, M. S., Ribeiro, A. A.,
      Doerrler, W. T., Lin, S., Cotter, R. J., and Raetz, C. R. H. (2001) J. Biol.
      Chem. 276, 43132-43144), ArnT utilizes the novel lipid undecaprenyl phosphate
      alpha-l-Ara4N as its sugar donor, suggesting that l-Ara4N transfer to lipid A
      occurs on the periplasmic side of the inner membrane.

PMID- 11535605
TI  - Accumulation of a polyisoprene-linked amino sugar in polymyxin-resistant
      Salmonella typhimurium and Escherichia coli: structural characterization and
      transfer to lipid A in the periplasm.
AB  - Polymyxin-resistant mutants of Escherichia coli and Salmonella typhimurium
      accumulate a novel minor lipid that can donate 4-amino-4-deoxy-l-arabinose units
      (l-Ara4N) to lipid A. We now report the purification of this lipid from a pss(-)
      pmrA(C) mutant of E. coli and assign its structure as undecaprenyl phosphate
      alpha-l-Ara4N. Approximately 0.2 mg of homogeneous material was isolated from an
      8-liter culture by solvent extraction, followed by chromatography on DEAE
      cellulose, C18 reverse phase resin, and silicic acid. Matrix-assisted laser
      desorption ionization/time of flight mass spectrometry in the negative mode
      yielded a single species [M - H](-) at m/z 977.5, consistent with undecaprenyl
      phosphate-alpha-l-Ara4N (M(r) = 978.41). (31)P NMR spectroscopy showed a single
      phosphorus atom at -0.44 ppm characteristic of a phosphodiester linkage.
      Selective inverse decoupling difference spectroscopy demonstrated that the
      undecaprenyl phosphate group is attached to the anomeric carbon of the l-Ara4N
      unit. One- and two-dimensional (1)H NMR studies confirmed the presence of a
      polyisoprene chain and a sugar moiety with chemical shifts and coupling constants
      expected for an equatorially substituted arabinopyranoside. Heteronuclear
      multiple-quantum coherence spectroscopy analysis demonstrated that a nitrogen
      atom is attached to C-4 of the sugar residue. The purified donor supports in
      vitro conversion of lipid IV(A) to lipid II(A), which is substituted with a
      single l-Ara4N moiety. The identification of undecaprenyl phosphate-alpha-l-Ara4N
      implies that l-Ara4N transfer to lipid A occurs in the periplasm of polymyxin
      resistant strains, and establishes a new enzymatic pathway by which Gram-negative
      bacteria acquire antibiotic resistance.

PMID- 11535606
TI  - Agonist-promoted internalization of a ternary complex between calcitonin receptor
      like receptor, receptor activity-modifying protein 1 (RAMP1), and beta-arrestin.
AB  - The calcitonin receptor-like receptor (CRLR) is a seven-transmembrane domain
      (7TM) protein that requires the receptor activity-modifying protein 1 (RAMP1) to
      be expressed at the cell surface as a functional calcitonin gene-related peptide
      (CGRP) receptor. Although dimerization between the two molecules is well
      established, very little is known concerning the trafficking of this heterodimer
      upon receptor activation. Also, the subcellular localization and biochemical
      state of this ubiquitously expressed protein, in the absence of CRLR, remains
      poorly characterized. Here we report that when expressed alone RAMP1 is retained
      inside the cells where it is found in the endoplasmic reticulum and the Golgi
      predominantly as a disulfide-linked homodimer. In contrast, when expressed with
      CRLR, it is targeted to the cell surface as a 1:1 heterodimer with the 7TM
      protein. Although heterodimer formation does not involve intermolecular disulfide
      bonds, RAMP-CRLR association promotes the formation of intramolecular disulfide
      bonds within RAMP1. CGRP binding and receptor activation lead to the
      phosphorylation of CRLR and the internalization of the receptor as a stable
      complex. The internalization was found to be both dynamin- and beta-arrestin
      dependent, indicating that the formation of a ternary complex between CRLR,
      RAMP1, and beta-arrestin leads to clathrin-coated pit-mediated endocytosis. These
      results therefore indicate that although atypical by its heterodimeric
      composition and its targeting to the plasma membrane, the CGRP receptor shares
      endocytotic mechanisms that are common to most classical 7TM receptors.

PMID- 11535607
TI  - Crystal structure of the tumor-promoter okadaic acid bound to protein phosphatase
      1.
AB  - Protein phosphatase-1 (PP1) plays a key role in dephosphorylation in numerous
      biological processes such as glycogen metabolism, cell cycle regulation, smooth
      muscle contraction, and protein synthesis. Microorganisms produce a variety of
      inhibitors of PP1, which include the microcystin class of inhibitors and okadaic
      acid, the latter being the major cause of diarrhetic shellfish poisoning and a
      powerful tumor promoter. We have determined the crystal structure of the
      molecular complex of okadaic acid bound to PP1 to a resolution of 1.9 A. This
      structure reveals that the acid binds in a hydrophobic groove adjacent to the
      active site of the protein and interacts with basic residues within the active
      site. Okadaic acid exhibits a cyclic structure, which is maintained via an
      intramolecular hydrogen bond. This is reminiscent of other macrocyclic protein
      phosphatase inhibitors. The inhibitor-bound enzyme shows very little
      conformational change when compared with two other PP1 structures, except in the
      inhibitor-sensitive beta12-beta13 loop region. The selectivity of okadaic acid
      for protein phosphatases-1 and -2A but not PP-2B (calcineurin) may be reassessed
      in light of this study.

PMID- 11535608
TI  - Human neutrophil lactoferrin trans-activates the matrix metalloproteinase 1 gene
      through stress-activated MAPK signaling modules.
AB  - It has been proposed that human neutrophil lactoferrin (Lf) could be involved in
      gene expression as a DNA-binding protein after its translocation into the
      nucleus. However, the molecular basis of Lf action has not been defined, and Lf
      regulated target genes have not been identified. We report here that
      overexpressed Lf functions as a specific trans-activator of matrix
      metalloproteinase 1 (MMP1) gene, and that induction of this AP-1-responsive gene
      is mediated via the stress-activated MAPK signaling modules. Transactivation of
      the MMP1 promoter by overexpressed Lf requires the presence of an AP-1 binding
      site. In gel shift experiments, Lf did not interact directly with AP-1-containing
      fragments of the MMP1 promoter. However, nuclear extracts from Lf-expressing
      cells contained increased levels of proteins that bound to AP-1 elements. This Lf
      induced AP-1 DNA binding activity was reduced by a p38 MAPK inhibitor. Inhibitors
      of the MEK kinases had little effect on Lf-induced AP-1. However, expression of
      dominant-negative MKK4 or JNK1 inhibited Lf-induced gene expression. The JNK
      activity stimulated by Lf correlates with the enhanced AP-1 binding ability.
      These findings demonstrate that the Lf-induced activation of AP-1 is mediated via
      JNK and p38 MAPK pathways.

PMID- 11535614
TI  - A new view of the spindle checkpoint.
AB  - Previous studies of the spindle checkpoint suggested that its ability to prevent
      entry into anaphase was mediated by the inhibition of the anaphase-promoting
      complex (APC) ubiquitin ligase by Mad2. Two new studies challenge that view by
      demonstrating that another checkpoint protein, BubR1, is a far more potent
      inhibitor of APC function.

PMID- 11535615
TI  - Activation of mammalian Chk1 during DNA replication arrest: a role for Chk1 in
      the intra-S phase checkpoint monitoring replication origin firing.
AB  - Checkpoints maintain order and fidelity in the cell cycle by blocking late
      occurring events when earlier events are improperly executed. Here we describe
      evidence for the participation of Chk1 in an intra-S phase checkpoint in
      mammalian cells. We show that both Chk1 and Chk2 are phosphorylated and activated
      in a caffeine-sensitive signaling pathway during S phase, but only in response to
      replication blocks, not during normal S phase progression. Replication block
      induced activation of Chk1 and Chk2 occurs normally in ataxia telangiectasia (AT)
      cells, which are deficient in the S phase response to ionizing radiation (IR).
      Resumption of synthesis after removal of replication blocks correlates with the
      inactivation of Chk1 but not Chk2. Using a selective small molecule inhibitor,
      cells lacking Chk1 function show a progressive change in the global pattern of
      replication origin firing in the absence of any DNA replication. Thus, Chk1 is
      apparently necessary for an intra-S phase checkpoint, ensuring that activation of
      late replication origins is blocked and arrested replication fork integrity is
      maintained when DNA synthesis is inhibited.

PMID- 11535616
TI  - Checkpoint inhibition of the APC/C in HeLa cells is mediated by a complex of
      BUBR1, BUB3, CDC20, and MAD2.
AB  - The mitotic checkpoint prevents cells with unaligned chromosomes from prematurely
      exiting mitosis by inhibiting the anaphase-promoting complex/cyclosome (APC/C)
      from targeting key proteins for ubiquitin-mediated proteolysis. We have examined
      the mechanism by which the checkpoint inhibits the APC/C by purifying an APC/C
      inhibitory factor from HeLa cells. We call this factor the mitotic checkpoint
      complex (MCC) as it consists of hBUBR1, hBUB3, CDC20, and MAD2 checkpoint
      proteins in near equal stoichiometry. MCC inhibitory activity is 3,000-fold
      greater than that of recombinant MAD2, which has also been shown to inhibit APC/C
      in vitro. Surprisingly, MCC is not generated from kinetochores, as it is also
      present and active in interphase cells. However, only APC/C isolated from mitotic
      cells was sensitive to inhibition by MCC. We found that the majority of the APC/C
      in mitotic lysates is associated with the MCC, and this likely contributes to the
      lag in ubiquitin ligase activity. Importantly, chromosomes can suppress the
      reactivation of APC/C. Chromosomes did not affect the inhibitory activity of MCC
      or the stimulatory activity of CDC20. We propose that the preformed interphase
      pool of MCC allows for rapid inhibition of APC/C when cells enter mitosis.
      Unattached kinetochores then target the APC/C for sustained inhibition by the
      MCC.

PMID- 11535617
TI  - The nucleoporin Nup60p functions as a Gsp1p-GTP-sensitive tether for Nup2p at the
      nuclear pore complex.
AB  - The nucleoporins Nup60p, Nup2p, and Nup1p form part of the nuclear basket
      structure of the Saccharomyces cerevisiae nuclear pore complex (NPC). Here, we
      show that these necleoporins can be isolated from yeast extracts by affinity
      chromatography on karyopherin Kap95p-coated beads. To characterize Nup60p
      further, Nup60p-coated beads were used to capture its interacting proteins from
      extracts. We find that Nup60p binds to Nup2p and serves as a docking site for
      Kap95p-Kap60p heterodimers and Kap123p. Nup60p also binds Gsp1p-GTP and its
      guanine nucleotide exchange factor Prp20p, and functions as a Gsp1p guanine
      nucleotide dissociation inhibitor by reducing the activity of Prp20p. Yeast
      lacking Nup60p exhibit minor defects in nuclear export of Kap60p, nuclear import
      of Kap95p-Kap60p-dependent cargoes, and diffusion of small proteins across the
      NPC. Yeast lacking Nup60p also fail to anchor Nup2p at the NPC, resulting in the
      mislocalization of Nup2p to the nucleoplasm and cytoplasm. Purified Nup60p and
      Nup2p bind each other directly, but the stability of the complex is compromised
      when Kap60p binds Nup2p. Gsp1p-GTP enhances by 10-fold the affinity between
      Nup60p and Nup2p, and restores binding of Nup2p-Kap60p complexes to Nup60p. The
      results suggest a dynamic interaction, controlled by the nucleoplasmic
      concentration of Gsp1p-GTP, between Nup60p and Nup2p at the NPC.

PMID- 11535618
TI  - Calcineurin-dependent nuclear import of the transcription factor Crz1p requires
      Nmd5p.
AB  - Calcineurin is a conserved Ca2+/calmodulin-specific serine-threonine protein
      phosphatase that mediates many Ca2+-dependent signaling events. In yeast,
      calcineurin dephosphorylates Crz1p, a transcription factor that binds to the
      calcineurin-dependent response element, a 24-bp promoter element. Calcineurin
      dependent dephosphorylation of Crz1p alters Crz1p nuclear localization. This
      study examines the mechanism by which calcineurin regulates the nuclear
      localization of Crz1p in more detail. We describe the identification and
      characterization of a novel nuclear localization sequence (NLS) in Crz1p, which
      requires both basic and hydrophobic residues for activity, and show that the
      karyopherin Nmd5p is required for Crz1p nuclear import. We also demonstrate that
      the binding of Crz1p to Nmd5p is dependent upon its phosphorylation state,
      indicating that nuclear import of Crz1p is regulated by calcineurin. Finally, we
      demonstrate that residues in both the NH2- and COOH-terminal portions of Crz1p
      are required for regulated Crz1p binding to Nmd5p, supporting a model of NLS
      masking for regulating Crz1p nuclear import.

PMID- 11535619
TI  - Phosphatidylinositol 4,5-bisphosphate and Arf6-regulated membrane traffic.
AB  - ADP-ribosylation factor (Arf) 6 regulates the movement of membrane between the
      plasma membrane (PM) and a nonclathrin-derived endosomal compartment and
      activates phosphatidylinositol 4-phosphate 5-kinase (PIP 5-kinase), an enzyme
      that generates phosphatidylinositol 4,5-bisphosphate (PIP2). Here, we show that
      PIP2 visualized by expressing a fusion protein of the pleckstrin homology domain
      from PLCdelta and green fluorescent protein (PH-GFP), colocalized with Arf6 at
      the PM and on tubular endosomal structures. Activation of Arf6 by expression of
      its exchange factor EFA6 stimulated protrusion formation, the uptake of PM into
      macropinosomes enriched in PIP2, and recycling of this membrane back to the PM.
      By contrast, expression of Arf6 Q67L, a GTP hydrolysis-resistant mutant, induced
      the formation of PIP2-positive actin-coated vacuoles that were unable to recycle
      membrane back to the PM. PM proteins, such as beta1-integrin, plakoglobin, and
      major histocompatibility complex class I, that normally traffic through the Arf6
      endosomal compartment became trapped in this vacuolar compartment. Overexpression
      of human PIP 5-kinase alpha mimicked the effects seen with Arf6 Q67L. These
      results demonstrate that PIP 5-kinase activity and PIP2 turnover controlled by
      activation and inactivation of Arf6 is critical for trafficking through the Arf6
      PM-endosomal recycling pathway.

PMID- 11535620
TI  - Protein kinase B phosphorylates AHNAK and regulates its subcellular localization.
AB  - AHNAK is a ubiquitously expressed giant phosphoprotein that was initially
      identified as a gene product subject to transcriptional repression in
      neuroblastoma. AHNAK is predominantly nuclear in cells of nonepithelial origin,
      but is cytoplasmic or associated with plasma membrane in epithelial cells. In
      this study we show that the extranuclear localization of AHNAK in epithelial
      cells depends on the formation of cell-cell contacts. We show that AHNAK is a
      phosphorylation substrate of protein kinase B (PKB) in vitro and in vivo. Nuclear
      exclusion of AHNAK is mediated through a nuclear export signal (NES) in a manner
      that depends on the phosphorylation of serine 5535 of AHNAK by PKB, a process
      that also plays a major role in determining extranuclear localization of AHNAK.
      AHNAK is a new PKB substrate whose function, though unknown, is likely to be
      regulated by its localization, which is in turn regulated by PKB.

PMID- 11535621
TI  - Kettin, a major source of myofibrillar stiffness in Drosophila indirect flight
      muscle.
AB  - Kettin is a high molecular mass protein of insect muscle that in the sarcomeres
      binds to actin and alpha-actinin. To investigate kettin's functional role, we
      combined immunolabeling experiments with mechanical and biochemical studies on
      indirect flight muscle (IFM) myofibrils of Drosophila melanogaster. Micrographs
      of stretched IFM sarcomeres labeled with kettin antibodies revealed staining of
      the Z-disc periphery. After extraction of the kettin-associated actin, the A-band
      edges were also stained. In contrast, the staining pattern of projectin, another
      IFM-I-band protein, was not altered by actin removal. Force measurements were
      performed on single IFM myofibrils to establish the passive length-tension
      relationship and record passive stiffness. Stiffness decreased within seconds
      during gelsolin incubation and to a similar degree upon kettin digestion with mu
      calpain. Immunoblotting demonstrated the presence of kettin isoforms in normal
      Drosophila IFM myofibrils and in myofibrils from an actin-null mutant. Dotblot
      analysis revealed binding of COOH-terminal kettin domains to myosin. We conclude
      that kettin is attached not only to actin but also to the end of the thick
      filament. Kettin along with projectin may constitute the elastic filament system
      of insect IFM and determine the muscle's high stiffness necessary for stretch
      activation. Possibly, the two proteins modulate myofibrillar stiffness by
      expressing different size isoforms.

PMID- 11535622
TI  - Deficiency of triad junction and contraction in mutant skeletal muscle lacking
      junctophilin type 1.
AB  - In skeletal muscle excitation-contraction (E-C) coupling, the depolarization
      signal is converted from the intracellular Ca2+ store into Ca2+ release by
      functional coupling between the cell surface voltage sensor and the Ca2+ release
      channel on the sarcoplasmic reticulum (SR). The signal conversion occurs in the
      junctional membrane complex known as the triad junction, where the invaginated
      plasma membrane called the transverse-tubule (T-tubule) is pinched from both
      sides by SR membranes. Previous studies have suggested that junctophilins (JPs)
      contribute to the formation of the junctional membrane complexes by spanning the
      intracellular store membrane and interacting with the plasma membrane (PM) in
      excitable cells. Of the three JP subtypes, both type 1 (JP-1) and type 2 (JP-2)
      are abundantly expressed in skeletal muscle. To examine the physiological role of
      JP-1 in skeletal muscle, we generated mutant mice lacking JP-1. The JP-1 knockout
      mice showed no milk suckling and died shortly after birth. Ultrastructural
      analysis demonstrated that triad junctions were reduced in number, and that the
      SR was often structurally abnormal in the skeletal muscles of the mutant mice.
      The mutant muscle developed less contractile force (evoked by low-frequency
      electrical stimuli) and showed abnormal sensitivities to extracellular Ca2+. Our
      results indicate that JP-1 contributes to the construction of triad junctions and
      that it is essential for the efficiency of signal conversion during E-C coupling
      in skeletal muscle.

PMID- 11535623
TI  - Proteolytic exposure of a cryptic site within collagen type IV is required for
      angiogenesis and tumor growth in vivo.
AB  - Evidence is provided that proteolytic cleavage of collagen type IV results in the
      exposure of a functionally important cryptic site hidden within its triple
      helical structure. Exposure of this cryptic site was associated with angiogenic,
      but not quiescent, blood vessels and was required for angiogenesis in vivo.
      Exposure of the HUIV26 epitope was associated with a loss of alpha1beta1 integrin
      binding and the gain of alphavbeta3 binding. A monoclonal antibody (HUIV26)
      directed to this site disrupts integrin-dependent endothelial cell interactions
      and potently inhibits angiogenesis and tumor growth. Together, these studies
      suggest a novel mechanism by which proteolysis contributes to angiogenesis by
      exposing hidden regulatory elements within matrix-immobilized collagen type IV.

PMID- 11535624
TI  - A novel fibronectin binding site required for fibronectin fibril growth during
      matrix assembly.
AB  - Fibronectin (FN) assembly into a fibrillar extracellular matrix is a stepwise
      process requiring participation from multiple FN domains. Fibril formation is
      regulated in part by segments within the first seven type III repeats (III1-7).
      To define the specific function(s) of this region, recombinant FNs (recFNs)
      containing an overlapping set of deletions were tested for the ability to
      assemble into fibrils. Surprisingly, recFN lacking type III repeat III1
      (FNDeltaIII1), which contains a cryptic FN binding site and has been suggested to
      be essential for fibril assembly, formed a matrix identical in all respects to a
      native FN matrix. Similarly, displacement of the cell binding domain in repeats
      III9-10 to a position close to the NH2-terminal assembly domain, as well as a
      large deletion spanning repeats III4-7, had no effect on assembly. In contrast,
      two deletions that included repeat III2, DeltaIII1-2 and DeltaIII2-5, caused
      significant reductions in fibril elongation, although binding of FN to the cell
      surface and initiation of assembly still proceeded. Using individual repeats in
      binding assays, we show that III2 but not III1 contains an FN binding site. Thus,
      these results pinpoint repeat III2 as an important module for FN-FN interactions
      during fibril growth.

PMID- 11535625
TI  - Joining chain-expressing and -nonexpressing B cell populations in the mouse.
AB  - The diphtheria toxin A chain (DTA) was gene targeted into the Joining chain (J
      chain) locus to create a mouse strain selecting against J chain-expressing cells,
      JDTA mice. Serum immunoglobulin (Ig)M and serum IgG were reduced six to
      eightfold, while serum IgA was elevated 14-fold in these mice. JDTA mice were
      immune competent although the serum Ig response compared with wild-type mice was
      reduced sixfold at day 14 but only fourfold at day 45 after immunization.
      Exchanging the DTA gene with a cDNA for c-myc resulted in mice with a distinct
      phenotype with increased Ig production and enhanced humoral immune responses.
      Analysis of single B cells stimulated by lipopolysaccharide in vitro using
      reverse transcription-polymerase chain reaction showed that J chain-nonexpressing
      B cells could be detected that had a secretory phenotype as determined by an
      abundance of transcript for secretory IgM. Finally, limiting dilution analysis of
      peripheral B cells showed that J chain expression was a clonal property already
      established in naive, peripheral B lymphocytes.

PMID- 11535626
TI  - Eliciting the low-activity aldehyde dehydrogenase Asian phenotype by an antisense
      mechanism results in an aversion to ethanol.
AB  - A mutation in the gene encoding for the liver mitochondrial aldehyde
      dehydrogenase (ALDH2-2), present in some Asian populations, lowers or abolishes
      the activity of this enzyme and results in elevations in blood acetaldehyde upon
      ethanol consumption, a phenotype that greatly protects against alcohol abuse and
      alcoholism. We have determined whether the administration of antisense
      phosphorothioate oligonucleotides (ASOs) can mimic the low-activity ALDH2-2 Asian
      phenotype. Rat hepatoma cells incubated for 24 h with an antisense
      oligonucleotide (ASO-9) showed reductions in ALDH2 mRNA levels of 85% and ALDH2
      (half-life of 22 h) activity of 55% equivalent to a >90% inhibition in ALDH2
      synthesis. Glutamate dehydrogenase mRNA and activity remained unchanged. Base
      mismatches in the oligonucleotide rendered ASO-9 virtually inactive, confirming
      an antisense effect. Administration of ASO-9 (20 mg/kg/day for 4 d) to rats
      resulted in a 50% reduction in liver ALDH2 mRNA, a 40% inhibition in ALDH2
      activity, and a fourfold (P < 0.001) increase in circulating plasma acetaldehyde
      levels after ethanol (1 g/kg) administration. Administration of ASO-9 to rats by
      osmotic pumps led to an aversion (-61%, P < 0.02) to ethanol. These studies
      provide a proof of principle that specific inhibition of gene expression can be
      used to mimic the protective effects afforded by the ALDH2-2 phenotype.

PMID- 11535627
TI  - FES-Cre targets phosphatidylinositol glycan class A (PIGA) inactivation to
      hematopoietic stem cells in the bone marrow.
AB  - A somatic mutation in the X-linked phosphatidylinositol glycan class A (PIGA)
      gene causes the loss of glycosyl phosphatidylinositol (GPI)-linked proteins on
      blood cells from patients with paroxysmal nocturnal hemoglobinuria. Because all
      blood cell lineages may be affected it is thought that the mutation occurs in a
      hematopoietic stem cell. In transgenic mice, germline transmission of an inactive
      Piga gene is embryonic lethal. To inactivate the murine Piga gene in early
      hematopoiesis we therefore chose conditional gene inactivation using the Cre/loxP
      system. We expressed Cre recombinase under the transcription regulatory sequences
      of the human c-fes gene. FES-Cre inactivated PIGA in hematopoietic cells of mice
      carrying a floxed Piga allele (LF mice). PIGA(-) cells were found in all
      hematopoietic lineages of definitive but not primitive hematopoiesis. Their
      proportions were low in newborn mice but subsequently increased continuously to
      produce for the first time mice that have almost exclusively PIGA(-) blood cells.
      The loss of GPI-linked proteins occurred mainly in c-kit(+)CD34(+)Lin(-)
      progenitor cells before the CFU-GEMM stage. Using bone marrow reconstitution
      experiments with purified PIGA(-) cells we demonstrate that LF mice have long
      term bone marrow repopulating cells that lack GPI-linked proteins, indicating
      that recombination of the floxed Piga allele occurs in the hematopoietic stem
      cell.

PMID- 11535628
TI  - T cell homeostasis: thymus regeneration and peripheral T cell restoration in mice
      with a reduced fraction of competent precursors.
AB  - We developed a novel experimental strategy to study T cell regeneration after
      bone marrow transplantation. We assessed the fraction of competent precursors
      required to repopulate the thymus and quantified the relationship between the
      size of the different T cell compartments during T cell maturation in the thymus.
      The contribution of the thymus to the establishment and maintenance of the
      peripheral T cell pools was also quantified. We found that the degree of thymus
      restoration is determined by the availability of competent precursors and that
      the number of double-positive thymus cells is not under homeostatic control. In
      contrast, the sizes of the peripheral CD4 and CD8 T cell pools are largely
      independent of the number of precursors and of the number of thymus cells.
      Peripheral "homeostatic" proliferation and increased export and/or survival of
      recent thymus emigrants compensate for reduced T cell production in the thymus.
      In spite of these reparatory processes, mice with a reduced number of mature T
      cells in the thymus have an increased probability of peripheral T cell
      deficiency, mainly in the naive compartment.

PMID- 11535629
TI  - Fuc-TVII is required for T helper 1 and T cytotoxic 1 lymphocyte selectin ligand
      expression and recruitment in inflammation, and together with Fuc-TIV regulates
      naive T cell trafficking to lymph nodes.
AB  - To determine how the alpha(1,3)fucosyltransferases Fuc-TIV and Fuc-TVII, and the
      selectin ligands they control may contribute to the adaptive immune response,
      contact hypersensitivity (CHS) was characterized in mice deficient in either or
      both enzymes. We find a substantial CHS deficiency in Fuc-TVII(-/-) mice, and a
      complete deficiency in Fuc-TIV(-/-)/Fuc-TVII(-/-) mice. These defects are not
      accounted for by alterations in the number or function of epidermal Langerhans
      cells required for cutaneous antigen processing and presentation. By contrast,
      defective CHS in Fuc-TVII(-/-) mice or Fuc-TIV(-/-)/Fuc-TVII(-/-) mice is
      attributed in part to prominent, or nearly complete deficiencies, respectively,
      in the complement of naive T lymphocytes available in lymph nodes for antigen
      dependent activation, expansion, differentiation, and dissemination. Fuc-TVII
      deficiency also deletes expression of E- and P-selectin ligands by Th1 and T
      cytotoxic 1 (Tc1) lymphocytes, annuls T cell trafficking to inflamed cutaneous
      sites in vivo, and thereby controls an essential component of the efferent phase
      of the cutaneous immune response. These observations indicate that collaborative
      contributions of Fuc-TIV and Fuc-TVII to L-selectin ligand synthesis, and to
      lymphocyte recruitment, are requisite components of the primary cellular immune
      response, and assign an essential role to Fuc-TVII in control of E- and P
      selectin ligand expression by Th1 and Tc1 lymphocytes.

PMID- 11535630
TI  - Overexpression of CD40 ligand in murine epidermis results in chronic skin
      inflammation and systemic autoimmunity.
AB  - CD40-CD40 ligand (L) interactions play a pivotal role in immune-mediated
      inflammatory responses via the activation of antigen-presenting cells (APCs). To
      investigate the effects of continuous activation of resident tissue APCs, in this
      case the Langerhans cells (LCs) of the skin, CD40L expression was targeted to the
      basal keratinocytes of the epidermis of mice using the keratin-14 promoter.
      Approximately 80% of the transgenic (Tg) mice spontaneously developed dermatitis
      on the ears, face, tail, and/or paws. Compared with littermates, Tgs had a >90%
      decrease in epidermal LCs yet increased numbers within the dermis suggestive of
      enhanced emigration of CD40-activated LCs. Tgs also displayed massive regional
      lymphadenopathy with increased numbers of dendritic cells and B cells. Moreover,
      a decrease in IgM and an increase in IgG1/IgG2a/IgG2b/IgE serum concentrations
      was detectable. Screening for autoantibodies revealed the presence of antinuclear
      antibodies and anti-dsDNA antibodies implicative of systemic autoimmunity.
      Accordingly, renal Ig deposits, proteinuria, and lung fibrosis were observed.
      Adoptive transfer of T cells from Tgs to nonTg recipients evoked the development
      of skin lesions similar to those found in the Tgs. Dermatitis also developed in B
      cell-deficient CD40L Tg mice. These findings suggest that in situ activation of
      LCs by CD40L in the skin not only leads to chronic inflammatory dermatitis but
      also to systemic mixed-connective-tissue-like autoimmune disorders, possibly by
      breaking immune tolerance against the skin.

PMID- 11535631
TI  - Cell contact-dependent immunosuppression by CD4(+)CD25(+) regulatory T cells is
      mediated by cell surface-bound transforming growth factor beta.
AB  - CD4(+)CD25(+) T cells have been identified as a population of immunoregulatory T
      cells, which mediate suppression of CD4(+)CD25(-) T cells by cell-cell contact
      and not secretion of suppressor cytokines. In this study, we demonstrated that
      CD4(+)CD25(+) T cells do produce high levels of transforming growth factor (TGF)
      beta1 and interleukin (IL)-10 compared with CD4(+)CD25(-) T cells when stimulated
      by plate-bound anti-CD3 and soluble anti-CD28 and/or IL-2, and secretion of TGF
      beta1 (but not other cytokines), is further enhanced by costimulation via
      cytotoxic T lymphocyte-associated antigen (CTLA)-4. As in prior studies, we found
      that CD4(+)CD25(+) T cells suppress proliferation of CD4(+)CD25(-) T cells;
      however, we observed here that such suppression is abolished by the presence of
      anti-TGF-beta. In addition, we found that CD4(+)CD25(+) T cells suppress B cell
      immunoglobulin production and that anti-TGF-beta again abolishes such
      suppression. Finally, we found that stimulated CD4(+)CD25(+) T cells but not
      CD4(+)CD25(-) T cells express high and persistent levels of TGF-beta1 on the cell
      surface. This, plus the fact that we could find no evidence that a soluble factor
      mediates suppression, strongly suggests that CD4(+)CD25(+) T cells exert
      immunosuppression by a cell-cell interaction involving cell surface TGF-beta1.

PMID- 11535632
TI  - Localized gene-specific induction of accessibility to V(D)J recombination induced
      by E2A and early B cell factor in nonlymphoid cells.
AB  - Accessibility of immunoglobulin (Ig) gene segments to V(D)J recombination is
      highly regulated and is normally only achieved in B cell precursors. We
      previously showed that ectopic expression of E2A or early B cell factor (EBF)
      with recombination activating gene (RAG) induces rearrangement of IgH and IgL
      genes in nonlymphoid cells. VkappaI genes throughout the locus were induced to
      rearrange after transfection with E2A, suggesting that the entire Vkappa locus
      was accessible. However, here we show that Ig loci are not opened globally but
      that recombination is localized. Gene families are interspersed in the D(H),
      Vkappa, and Vlambda loci, and we show that certain families and individual genes
      undergo high levels of recombination after ectopic expression of E2A or EBF,
      while other families within the same locus are not induced to rearrange.
      Furthermore, in some families, induction of germline transcription correlates
      with the level of induced recombination, while in others there is no correlation,
      suggesting that recombination is not simply initiated by induction of germline
      transcription. The induced repertoire seen at 24 hours does not change
      significantly over time indicating the absence of many secondary rearrangements
      and also suggesting a direct targeting mechanism. We propose that accessibility
      occurs in a local manner, and that binding sites for factors facilitating
      accessibility are therefore likely to be associated with individual gene
      segments.

PMID- 11535634
TI  - A pathogenic role for myelin-specific CD8(+) T cells in a model for multiple
      sclerosis.
AB  - Multiple sclerosis (MS) is a demyelinating disease of the central nervous system
      (CNS) characterized by plaques of infiltrating CD4(+) and CD8(+) T cells. Studies
      of MS and experimental autoimmune encephalomyelitis (EAE), an animal model of MS,
      focus on the contribution of CD4(+) myelin-specific T cells. The role of CD8(+)
      myelin-specific T cells in mediating EAE or MS has not been described previously.
      Here, we demonstrate that myelin-specific CD8(+) T cells induce severe CNS
      autoimmunity in mice. The pathology and clinical symptoms in CD8(+) T cell
      mediated CNS autoimmunity demonstrate similarities to MS not seen in myelin
      specific CD4(+) T cell-mediated EAE. These data suggest that myelin-specific
      CD8(+) T cells could function as effector cells in the pathogenesis of MS.

PMID- 11535633
TI  - Expression of the serpin serine protease inhibitor 6 protects dendritic cells
      from cytotoxic T lymphocyte-induced apoptosis: differential modulation by T
      helper type 1 and type 2 cells.
AB  - Dendritic cells (DCs) play a central role in the immune system as they drive
      activation of T lymphocytes by cognate interactions. However, as DCs express high
      levels of major histocompatibility complex class I, this intimate contact may
      also result in elimination of DCs by activated cytotoxic T lymphocytes (CTLs) and
      thereby limit induction of immunity. We show here that immature DCs are indeed
      susceptible to CTL-induced killing, but become resistant upon maturation with
      anti-CD40 or lipopolysaccharide. Protection is achieved by expression of serine
      protease inhibitor (SPI)-6, a member of the serpin family that specifically
      inactivates granzyme B and thereby blocks CTL-induced apoptosis. Anti-CD40 and
      LPS-induced SPI-6 expression is sustained for long periods of time, suggesting a
      role for SPI-6 in the longevity of DCs. Importantly, T helper 1 cells, which
      mature DCs and boost CTL immunity, induce SPI-6 expression and subsequent DC
      resistance. In contrast, T helper 2 cells neither induce SPI-6 nor convey
      protection, despite the fact that they trigger DC maturation with comparable
      efficiency. Our data identify SPI-6 as a novel marker for DC function, which
      protects DCs against CTL-induced apoptosis.

PMID- 11535635
TI  - Development of spontaneous autoimmune peripheral polyneuropathy in B7-2-deficient
      NOD mice.
AB  - An increasing number of studies have documented the central role of T cell
      costimulation in autoimmunity. Here we show that the autoimmune diabetes-prone
      nonobese diabetic (NOD) mouse strain, deficient in B7-2 costimulation, is
      protected from diabetes but develops a spontaneous autoimmune peripheral
      polyneuropathy. All the female and one third of the male mice exhibited limb
      paralysis with histologic and electrophysiologic evidence of severe demyelination
      in the peripheral nerves beginning at 20 wk of age. No central nervous system
      lesions were apparent. The peripheral nerve tissue was infiltrated with dendritic
      cells, CD4(+), and CD8(+) T cells. Finally, CD4(+) T cells isolated from affected
      animals induced the disease in NOD.SCID mice. Thus, the B7-2-deficient NOD mouse
      constitutes the first model of a spontaneous autoimmune disease of the peripheral
      nervous system, which has many similarities to the human disease, chronic
      inflammatory demyelinating polyneuropathy (CIDP). This model demonstrates that
      NOD mice have "cryptic" autoimmune defects that can polarize toward the nervous
      tissue after the selective disruption of CD28/B7-2 costimulatory pathway.

PMID- 11535636
TI  - CD8 expression up to the double-positive CD3(low/intermediate) stage of thymic
      differentiation is sufficient for development of peripheral functional cytotoxic
      T lymphocytes.
AB  - Control of CD8alpha transcription during development of alpha/beta T cell
      receptor (TCR) T lymphocytes is mediated by at least two distinct stage-specific
      cis-acting transcriptional mechanisms (i.e., enhancers). On the CD8alpha(-/-)
      knockout (KO) background, cis-mechanism I and cis-mechanism II together mediate
      appropriate stage- and sublineage-specific transgenic (Tg) CD8alpha expression
      and "rescue" development of peripheral CD8(+) single-positive (SP) cytotoxic T
      lymphocytes (CTLs). In contrast, on the wild-type (WT)/CD8(+/+) or CD8alpha(-/
      )KO backgrounds, a CD8alpha Tg directed by cis-mechanism I alone is activated
      during the double negative [DN] to double positive [DP] transition and expressed
      up to the CD3(low/intermediate) DP stage but not in more mature DP or SP
      thymocytes or peripheral T cells. As loss of cis mechanism I activity occurs
      around the onset of positive selection, it is possible that events associated
      with TCR/major histocompatibility complex (MHC) interactions and selection are
      involved in initiating these changes in CD8alpha transcription. To examine this
      issue, phenotypic and functional studies were performed for thymocytes and T
      cells of CD8alpha(-/-) KO mice that expressed a CD8alpha Tg under control of cis
      mechanism I only. Despite loss of CD8alpha expression at the DP
      CD3(low/intermediate) stage, increased populations of mature CD3(hi)CD4(-)CD8(-)
      thymocytes and CD3(+)CD4(-)CD8(-) peripheral T cells were detected. By several
      criteria, including MHC class I-restricted antigen recognition, these cells have
      at least partially undergone positive and negative selection. Therefore,
      initiation of selection and sublineage commitment are determined before loss of
      cis-mechanism I-mediated control of CD8alpha transcription. Further, CD8
      expression beyond the CD3(low/intermediate) DP thymic stage is not essential for
      CTL development in vivo or function.

PMID- 11535637
TI  - The biological activity of natural and mutant pTalpha alleles.
AB  - beta selection is a major checkpoint in early thymocyte differentiation, mediated
      by successful expression of the pre-T cell receptor (TCR) comprising the TCRbeta
      chain, CD3 proteins, and a surrogate TCRalpha chain, pTalpha. The mechanism of
      action of the pre-TCR is unresolved. In humans and mice, the pTalpha gene encodes
      two RNAs, pTalpha(a), and a substantially truncated form, pTalpha(b). This study
      shows that both are biologically active in their capacity to rescue multiple
      thymocyte defects in pTalpha(-/-) mice. Further active alleles of pTalpha include
      one that lacks both the major ectodomain and much of the long cytoplasmic tail
      (which is unique among antigen receptor chains), and another in which the
      cytoplasmic tail is substituted with the short tail of TCR Calpha. Thus, very
      little of the pTalpha chain is required for function. These data support a
      hypothesis that the primary role of pTalpha is to stabilize the pre-TCR, and that
      much of the conserved structure of pTalpha probably plays a critical regulatory
      role.

PMID- 11535638
TI  - Killing of dendritic cells: a life cut short or a purposeful death?

PMID- 11535639
TI  - Myelin-specific CD8 T cells in the pathogenesis of experimental allergic
      encephalitis and multiple sclerosis.

PMID- 11535640
TI  - Organ-specific autoimmune disease: a deficiency of tolerogenic stimulation.

PMID- 11535641
TI  - MHC variation and tissue transplantation in fish.
AB  - Major histocompatibility complex (MHC) genes were originally discovered because
      of their role in tissue rejection in mammals and have subsequently been
      implicated in the incidence of autoimmune diseases and resistance to infectious
      diseases. Here we present the first demonstration that a gene defined by
      molecular sequence in the fish MHC, specifically a class II locus, plays an
      important role in tissue rejection. This effect in the endangered Gila topminnows
      appears to be additive and depends on the number of MHC alleles shared between
      the host and the recipient fish of the scale transplants. In addition, there was
      lower success of scale transplants in MHC-matched individuals in a population
      with high microsatellite variation than in a population with low variation. This
      suggests that other loci, presumably other MHC loci, play a significant role in
      transplantation success in fishes, as they do in mammals.

PMID- 11535642
TI  - A narrow hybrid zone between two Cottus species in Wills Creek, Potomac drainage.
AB  - We describe a narrow hybrid zone between the mottled sculpin (Cottus b. bairdi)
      and the Blue Ridge sculpin (C. caeruleomentum). Seven characters (dorsal fin
      rays, pectoral fin rays, caudal base band condition, male spawning coloration,
      and one frequency and two fixed allozyme differences) distinguish the two taxa in
      the hybrid zone. C. caeruleomentum and C. b. bairdi diverged in these characters
      in allopatry as indicated by their distribution on opposite sides of the Atlantic
      Ohio divide. However, a stream capture placed these two taxa in secondary contact
      in Wills Creek, Potomac drainage (Atlantic slope). Allozyme data indicate the
      presence of post-F(1) hybrids in the zone of secondary contact. Changes in
      allozymes, morphology, and spawning coloration along a transect in Wills Creek
      reveal the hybrid zone is less than 20 river kilometers in length. Estimates of
      root mean square dispersal and gene flow tentatively suggest that selection is
      operating in the Wills Creek hybrid zone. C. b. bairdi and C. caeruleomentum are
      maintaining their identity in seven distinguishing characters on opposite ends of
      the hybrid zone revealing these two taxa are independent evolutionary lineages.

PMID- 11535643
TI  - Identification of the sex of a wide range of Carinatae birds by PCR using primer
      sets selected from chicken EE0.6 and its related sequences.
AB  - A 0.6 kb EcoRI fragment (EE0.6), cloned from the W chromosome of chickens, is a
      nonrepetitive sequence and contains an exonlike sequence, ET15, which is likely a
      part of a pseudogene. The EE0.6 sequence is conserved in all species of birds
      examined both in Carinatae and Ratitae. A counterpart sequence of EE0.6 is
      present on the Z chromosome. The extent of diversity between the W- and Z-linked
      sequences are variable among species. The W- and Z-linked EE0.6 sequences, cloned
      from 12 different species, were compared and four forward and three reverse
      primers were selected to amplify parts of the EE0.6 sequence by polymerase chain
      reaction (PCR). By choosing a suitable combination of primers for EE0.6 and a set
      of primers for a Z/W-common sequence, as an internal control, the sex of 36
      species belonging to 16 different orders of Carinatae could be determined clearly
      by PCR. The sex of two other species representing different orders could be
      determined by Southern blot hybridization using ET15 as a probe. For the two
      Ratitae species, emu and ostrich, EE0.6 sequences on W and Z chromosomes could
      not be distinguished either by PCR or Southern blotting.

PMID- 11535644
TI  - Mapping of a QTL for serum HDL cholesterol in the rabbit using AFLP technology.
AB  - The amplified fragment length polymorphism (AFLP) technique is a DNA technology
      that generates the so-called AFLP markers. These markers are genomic restriction
      fragments detected after two rounds of polymerase chain reaction (PCR) without
      prior knowledge of nucleotide sequence. Here we describe the first application of
      the AFLP technique in the rabbit. We have tested two primer combinations. The
      results obtained with the DNA from rabbits of different breeds justify the
      conclusion that AFLP analysis is an effective tool for genetic studies in the
      rabbit. In addition, we contribute to the linkage map of the rabbit by localizing
      two AFLP markers on rabbit linkage group VI (LG VI). For this purpose the progeny
      of a IIIVO/JU x [IIIVO/JU x AX/JU]F(1) backcross were genotyped for 12 AFLP
      markers and 3 LG VI classical markers [one coat color marker (e) and two
      biochemical markers (Es-1 and Est-2)]. AX/JU is a dietary cholesterol-susceptible
      (hyperresponding) inbred strain and IIIVO/JU is a dietary cholesterol resistant
      (hyporesponding) inbred strain. Moreover, it is possible to evoke dietary
      cholesterol-induced aorta atherosclerosis in a relatively short time period in
      AX/JU rabbits, in contrast to IIIVO/JU rabbits. A significant cosegregation was
      found between basal serum HDL cholesterol level (i.e., the level on a low
      cholesterol, control diet) and an AFLP marker on LG VI. It is concluded that one
      or more genes of LG VI are regulating the basal serum HDL cholesterol level in
      rabbits. Thus the present study with rabbits clearly illustrates the value of
      AFLP markers for the construction of linkage maps and mapping of quantitative
      trait loci (QTL).

PMID- 11535645
TI  - Triplet-repeat microsatellites shared among hard and soft pines.
AB  - Vascular plant species have shown a low level of microsatellite conservation
      compared to many animal species. Finding trans-specific microsatellites for
      plants may be improved by using a priori knowledge of genome organization.
      Fifteen triplet-repeat microsatellites from hard pine (Pinus taeda L.) were
      tested for trans-specific amplification across seven hard pines (P. palustris
      Mill., P. echinata Mill., P. radiata D. Don., P. patula Schiede et Deppe, P.
      halepensis Mill., P. kesiya Royle), a soft pine (P. strobus L.), and Picea rubens
      Sargent. Seven of 15 microsatellites had trans-specific amplification in both
      hard and soft pine subgenera. Two P. taeda microsatellites had conserved flanking
      regions and repeat motifs in all seven hard pines, soft pine P. strobus, and P.
      rubens. Perfect triplet-repeat P. taeda microsatellites appear to be better
      candidates for trans-specific polymorphism than compound microsatellites. Not all
      perfect triplet-repeat microsatellites were conserved, but all conserved
      microsatellites had perfect repeat motifs. Persistent microsatellites PtTX2123
      and PtTX3020 had highly conserved flanking regions and a conserved repeat motif
      composition with variable repeat unit numbers. Using trinucleotide
      microsatellites improved trans-specific microsatellite recovery among hard and
      soft pine species.

PMID- 11535646
TI  - Independent spontaneous mitochondrial malate dehydrogenase null mutants in
      soybean are the result of deletions.
AB  - The mitochondrial malate dehydrogenase-1 (Mdh1) gene of soybean [Glycine max (L.)
      Merr.] spontaneously mutates to a null phenotype at a relatively high rate. To
      determine the molecular basis for the instability of the Mdh1 gene, the gene was
      cloned and sequenced. The null phenotype correlated with the deletion of specific
      genomic restriction fragments that encode the Mdh1 gene. The composition of the
      Mdh1 gene and its environs were compared with those of the more stable MDH2 gene.
      Several possible causes of the observed instability were found, including
      duplications, repeats, and two regions with similarity to a soybean catalase. The
      most likely cause of instability, however, appeared to be a 1233 bp region with
      58.9% identity to the Cyclops retrotransposons. Translation of a 714 bp segment
      of this region produced a peptide composed of 238 amino acid residues that showed
      35-40% identity and 55-60% similarity to several putative Cyclops gag-pol
      proteins (group-specific antigen polyprotein). This short peptide also contained
      a segment that corresponded to the protease active site of the gag-pol protein.
      Thus in an appropriate genetic background, a retrotransposon, whether whole or
      fractured, could promote genetic rearrangements.

PMID- 11535647
TI  - Genetic diversity of the Macaronesian leafy liverwort Porella canariensis
      inferred from RAPD markers.
AB  - Plant colonization of the North Atlantic raises the intriguing question of the
      relationships between extant island species with their continental counterparts
      (European, African, and American), which may provide clues to past geographic
      distribution and colonization history. It has been suggested that during past
      glaciations, many plant species with typical Mediterranean distributions survived
      in the Atlantic islands that belong to what is today known as Macronesia. We used
      random amplified polymorphic DNA (RAPD) markers to study 12 populations of the
      liverwort Porella canariensis partly covering its present-day distribution
      (Azores, Madeira, Canary and Cape Verde Islands, and Iberian Peninsula).
      Unweighted pair-group (UPGMA) and principal component (PCO) analyses showed a
      similar geographical pattern that suggested a close relationship between Iberian
      populations and those from the Canaries and Cape Verde Islands. Populations from
      Madeira had more genetic variation than those from the Azores, a result from
      either a richer diversity of habitats in Madeira, which prompted more population
      diversification, successive colonization waves from different origins, or an
      older colonization of Madeira. The data show that continuous patches of
      liverworts are often comprised of more than one individual. Finally, RAPDs can be
      used to investigate intraspecific diversity within a comparatively large
      geographic area and, with utmost care, can be used to infer a historic context to
      explain the patterns observed.

PMID- 11535648
TI  - Reproduction and recruitment in perennial colonies of the introduced wasp Vespula
      germanica.
AB  - We investigated the genetic structure of perennial colonies of the yellowjacket
      wasp (Vespula germanica) in its introduced range in Australia and New Zealand.
      The nuclear genotypes of 712 gynes from 21 colonies, 147 workers from 5 colonies,
      and 81 males from 4 colonies were assayed at three polymorphic microsatellite
      loci. The mitochondrial haplotypes of all wasps also were determined for a 450-bp
      region of the mtDNA using double-stranded conformational polymorphism (DSCP)
      analysis. We found that multiple reproductives were needed to explain the
      genotypes of gynes, workers, and males in 7 of 21, 2 of 5, and 2 of 4 colonies,
      respectively, and that nestmate relatedness of these three castes equaled 0.42,
      0.16, and 0.22, respectively. The mitochondrial data revealed that all
      individuals shared the same mtDNA haplotype in 20 of the 21 colonies. However, in
      one colony, gynes and workers displayed multiple mtDNA haplotypes, indicating
      that nonnestmate recruitment had occurred. Overall the genetic structure within
      the majority of perennial colonies conformed to expectations based on the biology
      of V. germanica and kin selection theory for polygyne colonies; multiple
      reproductives successfully produced offspring and were recruited into their natal
      nests, thereby maintaining relatively high relatedness between interacting
      individuals.

PMID- 11535649
TI  - Recombination between two amplified esterase alleles in Culex pipiens.
AB  - Esterase gene amplification at the Ester superlocus provides organophosphate
      resistance in the mosquito Culex pipiens (L.). In this study we explored the
      possibility of recombination between two amplified esterase alleles, thus
      generating a composite amplified allele. To do that, females heterozygous for two
      distinct amplified alleles (Ester(2) and Ester(4)) were crossed with males
      homozygous for a third resistance allele (Ester(8)). Among analyzed offspring,
      one recombinant composite allele (Ester(2-4)) was detected, providing a rate of
      recombination of approximately 0.2%. This is the first report of a recombination
      between two distinct amplified esterase alleles. This phenomenon renders the
      predictability of allele evolution considerably more complex than was previously
      thought.

PMID- 11535650
TI  - Unique mutations in mitochondrial DNA of senescence-accelerated mouse (SAM)
      strains.
AB  - Mitochondrial DNA (mtDNA) is exclusively inherited maternally and hence could
      offer a good method for tracing the lineage of mouse strains. We examined the
      mtDNA sequence of senescence-accelerated mouse (SAM) strains as well as other
      laboratory strains of inbred mice to deduce the ancestral strain of SAM. Four
      unique mutations were identified at bases 2256, 10,847, 11,181, and 13,053 in SAM
      strains. The mutations were not found in other mouse strains including AKR/J, one
      of the parental strains of SAM. Comparison of the mtDNA sequences also led to the
      consensus mtDNA sequence of laboratory strains of inbred mice. The seven
      laboratory strains of common inbred mice showed polymorphisms at base 9348,
      thymine repeat from base 9818, and adenine repeat from base 9821, and could be
      classified into five types by combination of the differences. Although we could
      not identify mouse strains with the same type of mtDNA as SAM in this study, the
      polymorphisms would provide a promising clue to ascertain the ancestral strain(s)
      of SAM. The polymorphism in mtDNA could be used to ascertain the genealogy of
      other mouse strains as well.

PMID- 11535651
TI  - Characterization of a major X-linked quantitative trait locus influencing body
      weight of mice.
AB  - Growth rate in mice is an archetypal quantitative trait that has long been
      studied genetically, physiologically, and metabolically, but its genetic basis is
      still poorly understood due to its complex inheritance and the influence of
      environment. We measured differences in 17 growth-related traits between a pair
      of partially congenic lines that differ for a segment of the X chromosome
      containing a quantitative trait locus (QTL) that we identified in a genomewide
      QTL scan. The QTL has a large effect on mean body weight of approximately 20% at
      all ages, and affects early growth rate to a greater extent than late growth
      rate. Feed is converted to body mass more efficiently in the high chromosome
      segment-bearing line than the low line. The weights of various internal organs
      are affected to a somewhat greater extent by the QTL than body weight. The
      proportional change in body length is smaller than body weight, but this may be
      an effect of scale. Body weight at late ages appears to allow the most efficient
      detection of allelic differences at the QTL, although assignment of genotypic
      state based on phenotype is never unambiguous.

PMID- 11535652
TI  - Non-sex-linked, nuclear cleaved amplified polymorphic sequences in Silene
      latifolia.
AB  - Cleaved amplified polymorphic sequences (CAPS) were identified for five nuclear
      genes in Silene latifolia. By using published cDNA sequences of S. latifolia,
      pairs of primers were designed to amplify small regions of six nuclear genes.
      Targeted regions were successfully amplified, two of which included introns. By
      using direct sequencing of diploid individuals, suitable polymorphic sites for
      CAPS markers were rapidly detected in five of six of these gene regions, thus
      avoiding the tedious screening of a large panel of restriction enzymes. Using
      controlled progenies, we have also shown that all these CAPS markers segregated
      independently of the sex phenotype, thus demonstrating that the genes analyzed
      here are not located in the nonrecombining region of the sex chromosomes.

PMID- 11535653
TI  - Banded polytene chromosomes in developing endosperm of pearl millet.
AB  - The occurrence of polyteny in the endosperm of field-grown plants as well as
      cultured endosperms of variety Vg272 of pearl millet (Pennisetum glaucum (L.)
      R.Br.) is recorded. There is a pronounced banded structure of these chromosomes
      similar to the ones observed in Dipteran salivary glands. Polyteny under
      physiologically controlled conditions also seems feasible in pearl millet.

PMID- 11535654
TI  - Phenotypic and genetic correlations among floral traits in two species of
      Thalictrum.
AB  - The evolution of dioecy in plants is expected to be followed by sex-specific
      selection, leading to sexual dimorphism. The extent of the response to selection
      depends on the genetic covariance structure between traits both within and
      between the sexes. Here I describe an investigation to determine phenotypic and
      genetic correlations between reproductive traits within cryptically dioecious
      Thalictrum pubescens and within morphologically dioecious T. dioicum. Females of
      T. pubescens produce flowers having stamens and pistils, appearing
      hermaphroditic. Genetic correlations were estimated as family-mean correlations
      among paternal half-sib families. Positive phenotypic and genetic correlations
      between parts of the same reproductive organs, as the anther and filament of the
      stamen, indicate developmental associations between these traits in both species.
      Negative genetic correlations were detected between pistil number and size of
      reproductive organs in T. dioicum and showed the same direction, but not
      significance, in T. pubescens. There was a negative phenotypic correlation
      between the number of stamens and the number of pistils within female flowers of
      T. pubescens. Within T. pubescens, there was a positive genetic correlation
      between the number of stamens in males and the number of pistils in females,
      indicating that floral evolution in males and females may not be independent in
      this species.

PMID- 11535655
TI  - SAS applications for Tai's stability analysis and AMMI model in genotype x
      environmental interaction (GEI) effects.
AB  - A user-friendly graphical data analysis to perform stability analysis of genotype
      x environmental interactions, using Tai's stability model and additive main
      effects and multiplicative interaction (AMMI) biplots, are presented here. This
      practical approach integrates statistical and graphical analysis tools available
      in SAS systems and provides user-friendly applications to perform complete
      stability analyses without writing SAS program statements or using pull-down menu
      interfaces by running the SAS macros in the background. By using this macro
      approach, the agronomists and plant breeders can effectively perform stability
      analysis and spend more time in data exploration, interpretation of graphs, and
      output, rather than debugging their program errors. The necessary MACRO-CALL
      files can be downloaded from the author's home page at http://www.ag.unr.edu/gf.
      The nature and the distinctive features of the graphics produced by these
      applications are illustrated by using published data.

PMID- 11535656
TI  - DAMBE: software package for data analysis in molecular biology and evolution.
AB  - DAMBE (data analysis in molecular biology and evolution) is an integrated
      software package for converting, manipulating, statistically and graphically
      describing, and analyzing molecular sequence data with a user-friendly Windows
      95/98/2000/NT interface. DAMBE is free and can be downloaded from
      http://web.hku.hk/~xxia/software/software.htm. The current version is 4.0.36.

PMID- 11535657
TI  - Activity in ventral and dorsal premotor cortex in response to predictable force
      pulse perturbations in a precision grip task.
AB  - This study compared the responses of ventral and dorsal premotor cortex (PMv and
      PMd) neurons to predictable force-pulse perturbations applied during a precision
      grip. Three monkeys were trained to grasp an unseen instrumented object between
      the thumb and index finger and to lift and hold it stationary within a position
      window for 2-2.5 s. The grip and load forces and the object displacement were
      measured on each trial. Single-unit activity was recorded from the hand regions
      in the PMv and PMd. In some conditions a predictable perturbation was applied to
      the object after 1,500 ms of static holding, whereas in other conditions
      different random combinations of perturbed and unperturbed trials were given. In
      the perturbed conditions, some were randomly and intermittently presented with a
      warning flash, whereas some were unsignaled. The activities of 198 cells were
      modulated during the task performance. Of these cells, 151 were located in the
      PMv, and 47 were located in the PMd. Although both PMv and PMd neurons had
      similar discharge patterns, more PMd neurons (84 vs. 43%) showed early pregrip
      activity. Forty of 106 PMv and 10/30 PMd cells responded to the perturbation with
      reflexlike triggered reactions. The latency of this response was always <100 ms
      with a mean of about 55 ms in both the PMv and the PMd. In contrast, 106 PMv and
      30 PMd cells tested with the perturbations, only 9 and 10%, respectively, showed
      significant but nonspecific adaptations to the perturbation. The warning stimulus
      did not increase the occurrence of specific responses to the perturbation even
      though 21 of 42 cells related to the grip task also responded to moving visual
      stimuli. The responses were retinal and frequently involved limited portions of
      both foveal and peripheral visual fields. When tested with a 75 x 5.5-cm dark bar
      on a light background, these cells were sensitive to the direction of movement.
      In summary, the periarcuate premotor area activity to related to predictable
      force-pulse perturbations seems to reflect a general increase in excitability in
      contrast to a more specific anticipatory activity such as recorded in the
      cerebellum. In spite of the strong cerebello-thalamo-cortical projections, the
      results of the present study suggest that the cortical premotor areas are not
      involved in the elaboration of adaptive internal models of hand-object dynamics.

PMID- 11535658
TI  - Activity in rostral motor cortex in response to predictable force-pulse
      perturbations in a precision grip task.
AB  - The purpose of this investigation was to characterize the discharge of neurons in
      the rostral area 4 motor cortex (MI) during performance of a precision grip task.
      Three monkeys were trained to grasp an object between the thumb and index finger
      and to lift and hold it stationary for 2-2.5 s within a narrow position window.
      The grip and load forces and the vertical displacement of the object were
      recorded on each trial. On some trials a downward force-pulse perturbation
      generating a shear force and slip on the skin was applied to the object after 1.5
      s of static holding. In total, 72 neurons were recorded near the rostral limit of
      the hand area of the motor cortex, located close to the premotor areas. Of these,
      30 neurons were examined for receptive fields, and all 30 were found to receive
      proprioceptive inputs from finger muscles. Intracortical microstimulation applied
      to 38 recording sites evoked brief hand movements, most frequently involving the
      thumb and index finger with an average threshold of 12 microA. Slightly more than
      one-half of the neurons (38/72) demonstrated significant increases in firing rate
      that on average began 284 +/- 186 ms before grip onset. Of 54 neurons tested with
      predictable force-pulse perturbations, 29 (53.7%) responded with a reflexlike
      reaction at a mean latency of 54.2 +/- 16.8 ms. This latency was 16 ms longer
      than the mean latency of reflexlike activity evoked in neurons with
      proprioceptive receptive fields in the more caudal motor cortex. No neurons
      exhibited anticipatory activity that preceded the perturbation even when the
      perturbations were delivered randomly and signaled by a warning stimulus. The
      results indicate the presence of a strong proprioceptive input to the rostral
      motor cortex, but raise the possibility that the afferent pathway or
      intracortical processing may be different because of the slightly longer latency.

PMID- 11535659
TI  - Reflex and intrinsic changes induced by fatigue of human elbow extensor muscles.
AB  - Fatigue-induced changes in intrinsic and reflex properties of human elbow
      extensor muscles and the underlying mechanisms for fatigue compensation were
      investigated. The elbow joint was perturbed using small-amplitude and
      pseudorandom movement patterns while subjects maintained steady levels of mean
      joint extension torque. Intrinsic and reflex properties were identified
      simultaneously using a nonlinear delay differential equation model. Intrinsic
      joint properties were characterized by measures of joint stiffness, viscous
      damping, and limb inertia and reflex properties characterized by measures of
      dynamic and static reflex gains. Fatigue was induced using 15 min of intermittent
      voluntary isometric (submaximal) exercise, and a rest period of 10 min was taken
      to allow the fatigued muscles to recover from acute fatigue effects. Identical
      experimental and data analysis procedures were used before and after fatigue. Our
      findings were that after fatigue, joint stiffness was significantly reduced at
      higher torque levels, presumably reflecting the reduced force-generating capacity
      of fatigued muscles. Conversely, joint viscosity was increased after fatigue
      potentially because of the reduced crossbridge detachment rate and prolonged
      relaxation associated with intracellular acidosis accompanying fatigue. Static
      stretch reflex gain decreased significantly at higher torque levels after
      fatigue, indicating that the isometric fatiguing exercise might be associated
      with a preferential change in properties of spindle chain fibers and bag(2)
      fibers. For matched pre- and postfatigue torque levels, dynamic reflexes
      contributed relatively more torque after fatigue, displaying higher dynamic
      reflex gains and larger dynamic electromyographic responses elicited by the
      controlled small-amplitude position perturbations. These changes appear to
      counteract the fatigue-induced reductions in joint stiffness and static reflex
      gain. The compensatory responses could be partly due to the effects of increasing
      the number of active motoneurons innervating the fatiguing muscles. This shift in
      operating point gave rise to significant compensation for the loss of contractile
      force. The compensation could also be due to fusimotor adjustment, which could
      make the dynamic reflex gain much less sensitive to fatigue than intrinsic
      stiffness. In short, the reduced contribution from intrinsic stiffness to joint
      torque was compensated by increased contribution from dynamic stretch reflexes
      after fatigue.

PMID- 11535660
TI  - Mechanisms underlying the depression of evoked fast EPSCs following in vitro
      ischemia in rat hippocampal CA1 neurons.
AB  - The mechanisms underlying the depression of evoked fast excitatory postsynaptic
      currents (EPSCs) following superfusion with medium deprived of oxygen and glucose
      (in vitro ischemia) for a 4-min period in hippocampal CA1 neurons were
      investigated in rat brain slices. The amplitude of evoked fast EPSCs decreased by
      85 +/- 7% of the control 4 min after the onset of in vitro ischemia. In contrast,
      the exogenous glutamate-induced inward currents were augmented, while the
      spontaneous miniature EPSCs obtained in the presence of tetrodotoxin (TTX, 1
      microM) did not change in amplitude during in vitro ischemia. In a normoxic
      medium, a pair of fast EPSCs was elicited by paired-pulse stimulation (40-ms
      interval), and the amplitude of the second fast EPSC increased to 156 +/- 24% of
      the first EPSC amplitude. The ratio of paired-pulse facilitation (PPF ratio)
      increased during in vitro ischemia. Pretreatment of the slices with adenosine 1
      (A1) receptor antagonist, 8-cyclopenthyltheophiline (8-CPT) antagonized the
      depression of the fast EPSCs, in a concentration-dependent manner: in the
      presence of 8-CPT (1-10 microM), the amplitude of the fast EPSCs decreased by
      only 20% of the control during in vitro ischemia. In addition, 8-CPT antagonized
      the enhancement of the PPF ratio during in vitro ischemia. A pair of presynaptic
      volleys and excitatory postsynaptic field potentials (fEPSPs) were
      extracellularly recorded in a proximal part of the stratum radiatum in the CA1
      region. The PPF ratio for the fEPSPs also increased during in vitro ischemia. On
      the other hand, the amplitudes of the first and second presynaptic volley, which
      were abolished by TTX (0.5 microM), did not change during in vitro ischemia. The
      maximal slope of the Ca(2+)-dependent action potential of the CA3 neurons, which
      were evoked in the presence of 8-CPT (1 microM), nifedipine (20 microM), TTX (0.5
      microM), and tetraethyl ammonium chloride (20 mM), decreased by 12 +/- 6% of the
      control 4 min after the onset of in vitro ischemia. These results suggest that in
      vitro ischemia depresses the evoked fast EPSCs mainly via the presynaptic A1
      receptors, and the remaining 8-CPT-resistant depression of the fast EPSCs is
      probably due to a direct inhibition of the Ca(2+) influx to the axon terminals.

PMID- 11535661
TI  - Synaptic noise improves detection of subthreshold signals in hippocampal CA1
      neurons.
AB  - Stochastic resonance (SR) is a phenomenon whereby the detection of a low-level
      signal is enhanced in a nonlinear system by the introduction of noise. Studies of
      the effects of SR in neurons have suggested that noise could play a prominent
      role in improving detection of small signals. Most experimental SR research has
      focused on the role of noise in sensory neurons using physiological stimuli.
      Computer simulations show that signal detection in hippocampal neurons is
      improved by the addition of physiological levels of noise applied extracellularly
      to synaptic inputs. These results were confirmed experimentally. We now report
      that endogenous noise sources can also improve signal detection. The noise source
      was generated by modulating the random synaptic activity on the apical dendrites
      of CA1 cells in rat hippocampal slices using subthreshold cathodic current.
      Intracellular recordings of CA1 cells showed that even small increases of
      synaptic noise are able to greatly improve the detection of an independent,
      synaptic, subthreshold stimulus as predicted by the simulations. The noise
      variance in the CA1 cell was compared with the resting variance and with variance
      changes caused by several endogenous noise sources. In all cases, the increased
      noise variance was well within the physiological range. These results were
      supplemented and analyzed with a CA1 computer model. The improved signal
      detection with small amounts of endogenous noise suggests that the diverse inputs
      to CA1 are able to improve detection of subthreshold synaptic signals and could
      provide a means to modulate detection of specific inputs in the hippocampus.

PMID- 11535662
TI  - Effects of auditory stimulus context on the representation of frequency in the
      gerbil inferior colliculus.
AB  - Prior studies of dynamic conditioning have focused on modulation of binaural
      localization cues, revealing that the responses of inferior colliculus (IC)
      neurons to particular values of interaural phase and level disparities depend
      critically on the context in which they occur. Here we show that monaural
      frequency transitions, which do not simulate azimuthal motion, also condition the
      responses of IC neurons. We characterized single-unit responses to two frequency
      transition stimuli: a glide stimulus comprising two tones linked by a linear
      frequency sweep (origin-sweep-target) and a step stimulus consisting of one tone
      followed immediately by another (origin-target). Using sets of glide and step
      stimuli converging on a common target, we constructed conditioned response
      functions (RFs) depicting the variability in the response to an identical
      stimulus as a function of the preceding origin frequency. For nearly all cells,
      the response to the target depended on the origin frequency, even for origins
      outside the excitatory frequency response area of the cell. Results from
      conditioned RFs based on long (2-4 s) and short (200 ms) duration step stimuli
      indicate that conditioning effects can be induced in the absence of the dynamic
      sweep, and by stimuli of relatively short duration. Because IC neurons are tuned
      to frequency, changes in the origin frequency often change the "effective"
      stimulus duty cycle. In many cases, the enhancement of the target response
      appeared related to the decrease in the "effective" stimulus duty cycle rather
      than to the prior presentation of a particular origin frequency. Although this
      implies that nonselective adaptive mechanisms are responsible for conditioned
      responses, slightly more than half of IC neurons in each paradigm responded
      significantly differently to targets following origins that elicited
      statistically indistinguishable responses. The prevailing influence of stimulus
      context when discharge history is controlled demonstrates that not all the
      mechanisms governing conditioning depend on the discharge history of the recorded
      neuron. Selective adaptation among the neuron's variously tuned afferents may
      help engender stimulus-specific conditioning. The demonstration that conditioning
      effects reflect sensitivity to spectral as well as spatial stimulus contrast has
      broad implications for the processing of a wide range of dynamic acoustic signals
      and sound sequences.

PMID- 11535663
TI  - Voltage-sensitivity of motoneuron NMDA receptor channels is modulated by
      serotonin in the neonatal rat spinal cord.
AB  - Both N-methyl-D-aspartate (NMDA) and serotonin (5-HT) receptors contribute to the
      generation of rhythmic motor patterns in the rat spinal cord. Co-application of
      these chemicals is more effective at producing locomotor-like activity than
      either neurochemical alone. In addition, NMDA application to rat spinal
      motoneurons, synaptically isolated in tetrodotoxin, induces nonlinear membrane
      behavior that results in voltage oscillations which can be blocked by 5-HT
      antagonists. However, the mechanisms underlying NMDA and 5-HT receptor
      interactions pertinent to motor rhythm production remain to be determined. In the
      present study, an in vitro neonatal rat spinal cord preparation was used to
      examine whether NMDA receptor-mediated nonlinear membrane voltage is modulated by
      5-HT. Whole-cell recordings of spinal motoneurons demonstrated that 5-HT shifts
      the region of NMDA receptor-dependent negative slope conductance (RNSC) of the
      current-voltage relationship to more hyperpolarized potentials and enhances whole
      cell inward current. The influence of 5-HT on the RNSC was similar to the effect
      on the RNSC of decreasing the extracellular Mg(2+)concentration. The results
      suggest that 5-HT may modulate this form of membrane voltage nonlinearity by
      regulating Mg(2+) blockade of the NMDA ionophore.

PMID- 11535664
TI  - Kinetics and activation of postsynaptic kainate receptors at thalamocortical
      synapses: role of glutamate clearance.
AB  - Kainate (KA) receptor-mediated excitatory postsynaptic currents (EPSCs) exhibit
      slow kinetics at the great majority of synapses. However, native or
      heterologously expressed KA receptors exhibit rapid kinetics in response to
      agonist application. One possibility to explain this discrepancy is that KA
      receptors are extrasynaptic and sense glutamate diffusing from the synaptic
      cleft. We investigated this by studying the effect of three manipulations that
      change glutamate clearance on evoked KA EPSCs at thalamocortical synapses. First,
      we used high-frequency stimulation to increase extrasynaptic glutamate levels.
      This caused an apparent increase in the relative contribution of the KA EPSC to
      transmission and slowed the decay kinetics. However, scaling and summing the EPSC
      evoked at low frequency reproduced this, demonstrating that the effect was due to
      postsynaptic summation of KA EPSCs. Second, we applied inhibitors of high
      affinity glutamate transport. This caused a depression in both AMPA and KA EPSC
      amplitude due to the activation of a presynaptic glutamatergic autoreceptor.
      However, transport inhibitors had no selective effect on the amplitude or
      kinetics of the KA EPSC. Third, to increase glutamate clearance, we raised
      temperature during recordings. This shortened the decay of both the AMPA and KA
      components and increased their amplitudes, but this effect was the same for both.
      Therefore these data provide evidence against glutamate diffusion out of the
      synaptic cleft as the mechanism for the slow kinetics of KA EPSCs. Other
      possibilities such as interactions of KA receptors with other proteins or novel
      properties of native synaptic heteromeric receptors are required to explain the
      slow kinetics.

PMID- 11535665
TI  - Dopamine D4 receptor activation inhibits presynaptically glutamatergic
      neurotransmission in the rat supraoptic nucleus.
AB  - Oxytocin and vasopressin release from magnocellular neurons of the supraoptic
      nucleus is under the control of glutamate-dependent excitation. The supraoptic
      nucleus also receives a generalized dopaminergic input from hypothalamic sources.
      To determine if dopamine can influence this excitatory drive onto the
      magnocellular neurons, we used whole-cell patch clamp to record the effect of
      dopamine on evoked and miniature excitatory postsynaptic currents in rat
      hypothalamic slices. Dopamine exposure (30 microM to 1 mM) induced a large and
      reversible reduction in the amplitude of evoked excitatory postsynaptic current
      in nearly all magnocellular cells tested. D4 receptors appeared to mediate
      dopamine's activity, based on inhibition of the response with 50 microM
      clozapine, but not by SCH 23390 or sulpiride, and mimicry of dopamine's action
      with the D4 specific agonist, PD 168077. Analysis of paired-pulse experiments and
      miniature postsynaptic currents indicated that dopamine's action involved a
      presynaptic mechanism, since the frequency of miniature postsynaptic currents was
      reduced with dopamine exposure without any change in current kinetics or
      amplitude, while the paired-pulse ratio increased. We therefore have demonstrated
      for the first time a role for dopamine D4 receptors in the supraoptic nucleus in
      the presynaptic inhibition of glutamatergic neurotransmission onto magnocellular
      neurons.

PMID- 11535666
TI  - E(f)-current contributes to whole-cell calcium current in low calcium in frog
      sympathetic neurons.
AB  - Because Ca(2+) plays diverse roles in intracellular signaling in neurons, several
      types of calcium channels are employed to control Ca(2+) influx in these cells.
      Our experiments focus on resolving the paradox of why whole-cell current has not
      been observed under typical recording conditions for one type of calcium channel
      that is highly expressed in frog sympathetic neurons. These channels, referred to
      as E(f)-channels, are present in the membrane at a density greater than the
      channels that carry approximately 90% of whole-cell current in low Ba(2+); but,
      E(f)-current has not been detected in low Ba(2+). Using Ca(2+) instead of Ba(2+)
      as the charge carrier, we recorded a possible E-type current in frog sympathetic
      neurons. The current was resistant to specific blockers of N-, L-, and P/Q-type
      calcium channels but was more sensitive to Ni(2+) block than was N- or L-current.
      Current amplitude in Ca(2+) is slightly greater than that in Ba(2+). In 3 mM
      Ca(2+), the current contributed approximately 12% of total current at peak
      voltage and increased at voltages more hyperpolarized to the peak, reaching
      approximately 40% at -30 mV, where whole-cell current starts to activate. The
      presence of E(f)-current in 3 mM Ca(2+) suggests a potential role for E(f)
      channels in regulating calcium influx into sympathetic neurons.

PMID- 11535667
TI  - Network and intrinsic contributions to carbachol-induced oscillations in the rat
      subiculum.
AB  - Low-frequency network oscillations occur in several areas of the limbic system
      where they contribute to synaptic plasticity and mnemonic functions that are in
      turn modulated by cholinergic mechanisms. Here we used slices of the rat
      subiculum (a limbic area involved in cognitive functions) to establish how
      network and single neuron (intrinsic) membrane mechanisms participate to the
      rhythmic oscillations elicited by the cholinergic agent carbachol (CCh, 50-100
      microM). We have found that CCh-induced network oscillations (intraoscillatory
      frequency = 5-16 Hz) are abolished by an antagonist of non-N-methyl-D-aspartate
      (NMDA) glutamatergic receptors (n = 6 slices) but persist during blockade of GABA
      receptors (n = 16). In addition, during application of glutamate and GABA
      receptor antagonists, single subicular cells generate burst oscillations at 2.1
      6.8 Hz when depolarized with steady current injection. These intrinsic burst
      oscillations disappear during application of a Ca(2+) channel blocker (n = 6
      cells), intracellular Ca(2+) chelation (n = 6), or replacement of extracellular
      Na(+) (n = 4) but persist in recordings made with electrodes containing a blocker
      of voltage-gated Na(+) channels (n = 7). These procedures cause similar effects
      on CCh-induced depolarizing plateau potentials that are contributed by a Ca(2+)
      activated nonselective cationic conductance (I(CAN)). Network and intrinsic
      oscillations along with depolarizing plateau potentials were abolished by the
      muscarinic receptor antagonist atropine. In conclusion, our findings demonstrate
      that low-frequency oscillations in the rat subiculum rely on the muscarinic
      receptor-dependent activation of an intrinsic oscillatory mechanism that is
      presumably contributed by I(CAN) and are integrated within the network via non
      NMDA receptor-mediated transmission.

PMID- 11535669
TI  - Time course of determination of movement direction in the reaction time task in
      humans.
AB  - The primary motor cortex produces motor commands that include encoding the
      direction of movement. Excitability of the motor cortex in the reaction time (RT)
      task can be assessed using transcranial magnetic stimulation (TMS). To elucidate
      the timing of the increase in cortical excitability and of the determination of
      movement direction before movement onset, we asked six right-handed, healthy
      subjects to either abduct or extend their right thumb after a go-signal indicated
      the appropriate direction. Between the go-signal and movement onset, single TMS
      pulses were delivered to the contralateral motor cortex. We recorded the
      direction of the TMS-induced thumb movement and the amplitude of motor-evoked
      potentials (MEPs) from the abductor pollicis brevis and extensor pollicis brevis
      muscles. Facilitation of MEPs from the prime mover, as early as 200 ms before the
      end of the reaction time, preceded facilitation of MEPs from the nonprime mover,
      and both preceded measurable directional change. Compared with a control
      condition in which no voluntary movement was required, the direction of the TMS
      induced thumb movement started to change in the direction of the intended
      movement as early as 90 ms before the end of the RT, and maximum changes were
      seen shortly before the end of reaction time. Movement acceleration also
      increased with maxima shortly before the end of the RT. We conclude that in
      concentric movements a change of the movement direction encoded in the primary
      motor cortex occurs in the 200 ms prior to movement onset, which is as early as
      increased excitability itself can be detected.

PMID- 11535668
TI  - NMDA antagonists in the superior colliculus prevent developmental plasticity but
      not visual transmission or map compression.
AB  - Partial ablation of the superior colliculus (SC) at birth in hamsters compresses
      the retinocollicular map, increasing the amount of visual field represented at
      each SC location. Receptive field sizes of single SC neurons are maintained,
      however, preserving receptive field properties in the prelesion condition. The
      mechanism that allows single SC neurons to restrict the number of convergent
      retinal inputs and thus compensate for induced brain damage is unknown. In this
      study, we examined the role of N-methyl-D-aspartate (NMDA) receptors in
      controlling retinocollicular convergence. We found that chronic 2-amino-5
      phosphonovaleric acid (APV) blockade of NMDA receptors from birth in normal
      hamsters resulted in enlarged single-unit receptive fields in SC neurons from
      normal maps and further enlargement in lesioned animals with compressed maps. The
      effect was linearly related to lesion size. These results suggest that NMDA
      receptors are necessary to control afferent/target convergence in the normal SC
      and to compensate for excess retinal afferents in lesioned animals. Despite the
      alteration in receptive field size in the APV-treated animals, a complete visual
      map was present in both normal and lesioned hamsters. Visual responsiveness in
      the treated SC was normal; thus the loss of compensatory plasticity was not due
      to reduced visual responsiveness. Our results argue that NMDA receptors are
      essential for map refinement, construction of receptive fields, and compensation
      for damage but not overall map compression. The results are consistent with a
      role for the NMDA receptor as a coincidence detector with a threshold, providing
      visual neurons with the ability to calculate the amount of visual space
      represented by competing retinal inputs through the absolute amount of
      coincidence in their firing patterns. This mechanism of population matching is
      likely to be of general importance during nervous system development.

PMID- 11535670
TI  - Electrophysiological evidence for vasopressin V(1) receptors on neonatal
      motoneurons, premotor and other ventral horn neurons.
AB  - Prominent arginine-vasopressin (AVP) binding and AVP V(1) type receptors are
      expressed early in the developing rat spinal cord. We sought to characterize
      their influence on neural excitability by using patch-clamp techniques to record
      AVP-induced responses from a population of motoneurons and interneurons in
      neonatal (5-18 days) rat spinal cord slices. Data were obtained from 58
      thoracolumbar (T(7)-L(5)) motoneurons and 166 local interneurons. A majority
      (>90%) of neurons responded to bath applied AVP (10 nM to 3 microM) and (Phe(2),
      Orn(8))-vasotocin, a V(1) receptor agonist, but not V(2) or oxytocin receptor
      agonists. In voltage-clamp, postsynaptic responses in motoneurons were
      characterized by slowly rising, prolonged (7-10 min) and tetrodotoxin-resistant
      inward currents associated with a 25% reduction in a membrane potassium
      conductance that reversed near -100 mV. In interneurons, net AVP-induced inward
      currents displayed three patterns: decreasing membrane conductance with reversal
      near -100 mV, i.e., similar to that in motoneurons (24 cells); increasing
      conductance with reversal near -40 mV (21 cells); small reduction in conductance
      with no reversal within the current range tested (41 cells). A presynaptic
      component recorded in most neurons was evident as an increase in the frequency
      but not amplitude (in motoneurons) of inhibitory and excitatory postsynaptic
      currents (IPSCs and EPSCs), in large part due to AVP-induced firing in inhibitory
      (mainly glycinergic) and excitatory (glutamatergic) neurons synapsing on the
      recorded cells. An increase in frequency but not amplitude of miniature IPSCs and
      EPSCs also indicated an AVP enhancement of neurotransmitter release from axon
      terminals of inhibitory and excitatory interneurons. These observations provide
      support for a broad presynaptic and postsynaptic distribution of AVP V(1) type
      receptors and indicate that their activation can enhance the excitability of a
      majority of neurons in neonatal ventral spinal cord.

PMID- 11535671
TI  - Genetic suppression of seizure susceptibility in Drosophila.
AB  - Despite the frequency of seizure disorders in the human population, the genetic
      and physiological basis for these defects has been difficult to resolve. Although
      many genetic defects that cause seizure susceptibility have been identified, the
      defects involve disparate biological processes, many of which are not neural
      specific. The large number and heterogeneous nature of the genes involved makes
      it difficult to understand the complex factors underlying the etiology of seizure
      disorders. Examining the effect known genetic mutations have on seizure
      susceptibility is one approach that may prove fruitful. This approach may be
      helpful both in understanding how different physiological processes affect
      seizure susceptibility and in identifying novel therapeutic treatments. In this
      study, we have taken advantage of Drosophila, a genetically tractable system, to
      identify factors that suppress seizure susceptibility. Of particular interest has
      been a group of Drosophila mutants, the bang-sensitive (BS) mutants, which are
      much more susceptible to seizures than wild type. The BS phenotypic class
      includes at least eight genes, including three examined in this study, bss, eas,
      and sda. Through the generation of double-mutant combinations with other well
      characterized Drosophila mutants, the BS mutants are particularly useful for
      identifying genetic factors that suppress susceptibility to seizures. We have
      found that mutants affecting Na+ channels, mle(napts) and para, K+ channels, Sh,
      and electrical synapses, shak-B(2), can suppress seizures in the BS mutants. This
      is the first demonstration that these types of mutations can suppress the
      development of seizures in any organism. Reduced neuronal excitability may
      contribute to seizure suppression. The best suppressor, mle(napts), causes an
      increased stimulation threshold for the giant fiber (GF) consistent with a
      reduction in single neuron excitability that could underlie suppression of
      seizures. For some other double mutants with para and Sh(KS133), there are no GF
      threshold changes, but reduced excitability may also be indicated by a reduction
      in GF following frequency. These results demonstrate the utility of Drosophila as
      a model system for studying seizure susceptibility and identify physiological
      processes that modify seizure susceptibility.

PMID- 11535672
TI  - Multiple sites of action potential initiation increase neuronal firing rate.
AB  - Sensory input to an individual interneuron or motoneuron typically evokes
      activity at a single site, the initial segment, so that firing rate reflects the
      balance of excitation and inhibition there. In a network of cells that are
      electrically coupled, a sensory input produced by appropriate, localized
      stimulation can cause impulses to be initiated in several places. An example in
      the leech is the chain of S cells, which are critical for sensitization of reflex
      responses to mechanosensory stimulation. S cells, one per segment, form an
      electrically coupled chain extending the entire length of the CNS. Each S cell
      receives input from mechanosensory neurons in that segment. Because impulses can
      arise in any S cell and can reliably propagate throughout the chain, all the S
      cells behave like a single neuron with multiple initiation sites. In the present
      experiments, well-defined stimuli applied to a small area of skin evoked
      mechanosensory action potentials that propagated centrally to several segments,
      producing S cell impulses in those segments. Following pressure to the skin,
      impulses arose first in the S cell of the same segment as the stimulus, followed
      by impulses in S cells in other segments. Often four or five separate initiation
      sites were observed. This timing of impulse initiation played an important role
      in increasing the frequency of firing. Impulses arising at different sites did
      not usually collide but added to the total firing rate of the chain. A
      computational model is presented to illustrate how mechanosensory neurons
      distribute the effects of a single sensory stimulus into spatially and temporally
      separated synaptic input. The model predicts that changes in impulse propagation
      in mechanosensory neurons can alter S cell frequency of firing by changing the
      number of initiation sites.

PMID- 11535673
TI  - Development of electrophysiological and morphological diversity in autonomic
      neurons.
AB  - The generation of neuronal diversity requires the coordinated development of
      differential patterns of ion channel expression along with characteristic
      differences in dendritic geometry, but the relations between these phenotypic
      features are not well known. We have used a combination of intracellular
      recordings, morphological analysis of dye-filled neurons, and stereological
      analysis of immunohistochemically labeled sections to investigate the development
      of characteristic electrical and morphological properties of functionally
      distinct populations of sympathetic neurons that project from the celiac ganglion
      to the splanchnic vasculature or the gastrointestinal tract of guinea pigs. At
      early fetal stages, neurons were significantly more depolarized at rest compared
      with neurons at later stages, and they generally fired only a single action
      potential. By mid fetal stages, rapidly and slowly adapting neurons could be
      distinguished with a topographic distribution matching that found in adult
      ganglia. Most rapidly adapting neurons (phasic neurons) at this age had a long
      afterhyperpolarization (LAH) characteristic of mature vasomotor neurons and were
      preferentially located in the lateral poles of the ganglion, where most neurons
      contained neuropeptide Y. Most early and mid fetal neurons showed a weak M
      current, which was later expressed only by rapidly-adapting and LAH neurons. Two
      different A currents were present in a subset of early fetal neurons and may
      indicate neurons destined to develop a slowly adapting phenotype (tonic neurons).
      The size of neuronal cell bodies increased at a similar rate throughout
      development regardless of their electrical or neurochemical phenotype or their
      topographical location. In contrast, the rate of dendritic growth of neurons in
      medial regions of the ganglion was significantly higher than that of neurons in
      lateral regions. The apparent cell capacitance was highly correlated with the
      surface area of the soma but not the dendritic tree of the developing neurons.
      These results demonstrate that the well-defined functional populations of neurons
      in the celiac ganglion develop their characteristic electrophysiological and
      morphological properties during early fetal stages of development. This is after
      the neuronal populations can be recognized by their neurochemical and
      topographical characteristics but long before the neurons have finished growing.
      Our data provide strong circumstantial evidence that the development of the full
      phenotype of different functional classes of autonomic final motor neurons is a
      multi-step process likely to involve a regulated sequence of trophic
      interactions.

PMID- 11535674
TI  - Membrane properties underlying patterns of GABA-dependent action potentials in
      developing mouse hypothalamic neurons.
AB  - Spikes may play an important role in modulating a number of aspects of brain
      development. In early hypothalamic development, GABA can either evoke action
      potentials, or it can shunt other excitatory activity. In both slices and
      cultures of the mouse hypothalamus, we observed a heterogeneity of spike patterns
      and frequency in response to GABA. To examine the mechanisms underlying patterns
      and frequency of GABA-evoked spikes, we used conventional whole cell and
      gramicidin perforation recordings of neurons (n = 282) in slices and cultures of
      developing mouse hypothalamus. Recorded with gramicidin pipettes, GABA
      application evoked action potentials in hypothalamic neurons in brain slices of
      postnatal day 2-9 (P2-9) mice. With conventional patch pipettes (containing 29 mM
      Cl-), action potentials were also elicited by GABA from neurons of 2-13 days in
      vitro (2-13 DIV) embryonic hypothalamic cultures. Depolarizing responses to GABA
      could be generally classified into three types: depolarization with no spike, a
      single spike, or complex patterns of multiple spikes. In parallel experiments in
      slices, electrical stimulation of GABAergic mediobasal hypothalamic neurons in
      the presence of glutamate receptor antagonists [10 microM 6-cyano-7
      nitroquinoxaline-2,3-dione (CNQX), 100 microM 2-amino-5-phosphonopentanoic acid
      (AP5)] resulted in the occurrence of spikes that were blocked by bicuculline (20
      microM). Blocking ionotropic glutamate receptors with AP5 and CNQX did not block
      GABA-mediated multiple spikes. Similarly, when synaptic transmission was blocked
      with Cd(2+) (200 microM) and Ni(2+) (300 microM), GABA still induced multiple
      spikes, suggesting that the multiple spikes can be an intrinsic membrane property
      of GABA excitation and were not based on local interneurons. When the pipette [Cl
      ] was 29 or 45 mM, GABA evoked multiple spikes. In contrast, spikes were not
      detected with 2 or 10 mM intracellular [Cl-]. With gramicidin pipettes, we found
      that the mean reversal potential of GABA-evoked current (E(GABA)) was positive to
      the resting membrane potential, suggesting a high intracellular [Cl-] in
      developing mouse neurons. Varying the holding potential from -80 to 0 mV revealed
      an inverted U-shaped effect on spike probability. Blocking voltage-dependent Na+
      channels with tetrodotoxin eliminated GABA-evoked spikes, but not the GABA-evoked
      depolarization. Removing Ca(2+) from the extracellular solution did not block
      spikes, indicating GABA-evoked Na+ -based spikes. Although E(GABA) was more
      positive within 2-5 days in culture, the probability of GABA-evoked spikes was
      greater in 6- to 9-day cells. Mechanistically, this appears to be due to a
      greater Na+ current found in the older cells during a period when the E(GABA) is
      still positive to the resting membrane potential. GABA evoked similar spike
      patterns in HEPES and bicarbonate buffers, suggesting that Cl-, not bicarbonate,
      was primarily responsible for generating multiple spikes. GABA evoked either
      single or multiple spikes; neurons with multiple spikes had a greater Na+
      current, a lower conductance, a more negative spike threshold, and a greater
      difference between the peak of depolarization and the spike threshold. Taken
      together, the present results indicate that the patterns of multiple action
      potentials evoked by GABA are an inherent property of the developing hypothalamic
      neuron.

PMID- 11535675
TI  - Synchronization of lower limb motor unit activity during walking in human
      subjects.
AB  - Synchronization of motor unit activity was investigated during treadmill walking
      (speed: 3-4 km/h) in 25 healthy human subjects. Recordings were made by pairs of
      wire electrodes inserted into the tibialis anterior (TA) muscle and by pairs of
      surface electrodes placed over this muscle and a number of other lower limb
      muscles (soleus, gastrocnemius lateralis, gastrocnemius medialis, biceps femoris,
      vastus lateralis, and vastus medialis). Short-lasting synchronization (average
      duration: 9.6 +/- 1.1 ms) was observed between spike trains generated from
      multiunit electromyographic (EMG) signals recorded by the wire electrodes in TA
      in eight of nine subjects. Synchronization with a slightly longer duration (12.8
      +/- 1.2 ms) was also found in 13 of 14 subjects for paired TA surface EMG
      recordings. The duration and size of this synchronization was within the same
      range as that observed during tonic dorsiflexion in sitting subjects. There was
      no relationship between the amount of synchronization and the speed of walking.
      Synchronization was also observed for pairs of surface EMG recordings from
      different ankle plantarflexors (soleus, medial gastrocnemius, and lateral
      gastrocnemius) and knee extensors (vastus lateralis and medialis of quadriceps),
      but not or rarely for paired recordings from ankle and knee muscles. The data
      demonstrate that human motor units within a muscle as well as synergistic muscles
      acting on the same joint receive a common synaptic drive during human gait. It is
      speculated that the common drive responsible for the motor unit synchronization
      during gait may be similar to that responsible for short-term synchronization
      during tonic voluntary contraction.

PMID- 11535676
TI  - Noise priming and the effects of different cochlear centrifugal pathways on loud
      sound-induced hearing loss.
AB  - Priming/conditioning the cochlea with moderately loud sound can reduce damage
      caused by subsequent loud sound. This study examined immediate effects of short
      term priming with monaural broadband noise on temporary threshold shifts (TTSs)
      in hearing caused by a subsequent loud high-frequency tone and the role of
      centrifugal olivocochlear pathways. Priming caused delay-dependent changes in
      tone-induced TTSs, particularly or only at frequencies higher than the peak tone
      affected frequency, through two general effects: a short-lasting increase in
      cochlear susceptibility to loud sound and longer-lasting complex end effects of
      centrifugal pathways. The results indicated the following points. Priming noise
      had "pure" cochlear effects, outlasting its presentation and declining with
      delay, that exacerbated tone-induced TTSs at frequencies higher than the peak
      tone-affected frequency. The centrifugal uncrossed medial olivocochlear system
      (UMOCS) could prevent this noise exacerbation and as this noise effect declined,
      could even reduce tone-induced TTSs below those to the unprimed tone. For longer
      delays, when priming noise no longer had any exacerbative "pure" cochlear effects
      on TTSs, UMOCS exacerbated TTSs above those to the unprimed tone. The crossed
      medial olivocochlear system (CMOCS) appeared to show a gradual "build-up" of
      effects postpriming. A parallel study showed it exercised no end effect on TTSs
      when noise and tone were concurrent. With priming, CMOCS effects were observed.
      For the shortest priming delay, the CMOCS blocked a UMOCS effect preventing noise
      exacerbation of tone-induced TTSs. For longer delays, CMOCS end effects, when
      present, reduced tone-induced TTSs below those to the unprimed tone. The CMOCS
      may oscillate between producing these effects and exerting no end-effect. With
      increasing delay CMOCS protection occurred in a greater proportion of animals.
      Finally, with a delay of 600 s between primer and loud tone, all these systems
      appeared to have reset to normal so that TTSs were similar to those in the
      unprimed condition. Thus the effects of short-term priming are not simple and do
      not suggest that centrifugal pathways act automatically as a protective system
      during such priming.

PMID- 11535677
TI  - Electrical stimuli patterned after the theta-rhythm induce multiple forms of LTP.
AB  - The induction of long-term potentiation (LTP) by high-frequency stimulation is
      considered an acceptable model for the study of learning and memory. In area CA1
      calcium influx through N-methyl-D-aspartate receptors (NMDARs; nmdaLTP) and/or L
      type voltage-dependent calcium channels (vdccLTP) results in distinct forms of
      LTP. In the light of significant accumulation of knowledge about patterns of
      naturally occurring activity in the intact animal, we examined whether the
      application of stimuli patterned after natural activity induced nmdaLTP and/or
      vdccLTP. In rat hippocampal slices we examined LTP induced by three types of
      patterned stimulation short (S-TBS), long (L-TBS), and high-intensity long theta
      patterned stimulation (HL-TBS). The patterns of stimulation were applied in
      control, nifedipine (blocks vdccLTP), D,L-2-amino-5-phosphonovaleric acid (APV;
      blocks nmdaLTP), or APV and nifedipine containing media. We found that S-TBS
      resulted in LTP that was completely attenuated in the presence of APV but was
      unaffected by nifedipine. Thus S-TBS results in the selective induction of
      nmdaLTP. L-TBS resulted in LTP that was completely blocked by APV and only
      partially blocked by nifedipine. Therefore L-TBS results in a compoundLTP
      consisting of both nmdaLTP and vdccLTP components. In the presence of APV, HL-TBS
      resulted in vdccLTP, and when APV and nifedipine were both present, LTP was
      completely blocked. Thus HL-TBS results in a vdccLTP in isolation when APV is
      present. We also examined saturation of S-TBS-induced LTP (nmdaLTP) by applying S
      TBS at short intervals. When nifedipine was present, multiple S-TBS trains
      resulted in a substantially smaller final LTP as compared with controls. We
      conclude that multiple bursts of S-TBS eventually summate to result in
      compoundLTP. Stimuli patterned after innate rhythms in the hippocampus
      effectively induce nmdaLTP (S-TBS), compoundLTP (L-TBS), or vdccLTP (HL-TBS).

PMID- 11535678
TI  - PP1 inhibitors depolarize Hermissenda photoreceptors and reduce K+ currents.
AB  - Previous research indicates that activation of protein kinase C (PKC) plays a
      critical role in the induction and maintenance of memory-related changes in
      neural excitability of Type B photoreceptors in the eyes of nudibranch mollusk
      Hermissenda crassicornis (H.c.). The enhanced excitability of B cells is due in
      part to PKC-mediated reduction in somatic K+ currents. Here we examined the
      effects of protein phosphatase inhibitors on Type B photoreceptor excitability
      and K+ currents to determine the role(s) of protein phosphatases on memory
      formation in Hermissenda. Using electrophysiological and pharmacological methods,
      we found that the PP1 inhibitors calyculin A and inhibitor-2 depolarized Type B
      photoreceptors by 20-30 mV. A broad-spectrum kinase inhibitor, H7, blocked this
      effect. The depolarization induced by PP1 inhibition occluded that produced by an
      in vitro associative conditioning procedure. Calyculin and inhibitor-2 reduced
      the same B cell K+ currents (I(A) and I(delayed)) that are reduced by in vitro
      and behavioral conditioning. H7 blocked the reductions. Cantharidic acid (PP2A
      inhibitor) and cyclosporin (PP2B inhibitor) had negligible effects on B cell
      resting membrane potential, K+ currents, and in vitro conditioning-produced
      cumulative depolarization of B cells. These results suggest that the functional
      activity of K+ channels in B cells is sustained by basal activity of PP1.
      Inhibiting PP1 appears to allow one or more constitutively active kinase(s) to
      reduce K+ channel activity and thus mimic the effects of conditioning. Our
      results suggest that PP1 may oppose and/or constrain the extent of learning
      produced changes in B cell excitability.

PMID- 11535679
TI  - Cellular mechanisms for amyloid beta-protein activation of rat cholinergic basal
      forebrain neurons.
AB  - The deposition of amyloid beta-protein (Abeta) in the brain and the loss of
      cholinergic neurons in the basal forebrain are two pathological hallmarks of
      Alzheimer's disease (AD). Although the mechanism of Abeta neurotoxicity is
      unknown, these cholinergic neurons display a selective vulnerability when exposed
      to this peptide. In this study, application of Abeta(25-35) or Abeta(1-40) to
      acutely dissociated rat neurons from the basal forebrain nucleus diagonal band of
      Broca (DBB), caused a decrease in whole cell voltage-activated currents in a
      majority of cells. This reduction in whole cell currents occurs through a
      modulation of a suite of potassium conductances including calcium-activated
      potassium (I(C)), the delayed rectifier (I(K)), and transient outward potassium
      (I(A)) conductances, but not calcium or sodium currents. Under current-clamp
      conditions, Abeta evoked an increase in excitability and a loss of accommodation
      in cholinergic DBB neurons. Using single-cell RT-PCR technique, we determined
      that Abeta actions were specific to cholinergic, but not GABAergic DBB neurons.
      Abeta effects on whole cell currents were occluded in the presence of membrane
      permeable protein tyrosine kinase inhibitors, genistein and tyrphostin B-44. Our
      data indicate that the Abeta actions on specific potassium conductances are
      modulated through a protein tyrosine kinase pathway and that these effects are
      selective to cholinergic but not GABAergic cells. These observations provide a
      cellular basis for the selectivity of Abeta neurotoxicity toward cholinergic
      basal forebrain neurons that are at the epicenter of AD pathology.

PMID- 11535680
TI  - Proprioceptive modulation of hip flexor activity during the swing phase of
      locomotion in decerebrate cats.
AB  - This study examined the influence of proprioceptive input from hip flexor muscles
      on the activity in hip flexors during the swing phase of walking in the
      decerebrate cat. One hindlimb was partially denervated to remove cutaneous input
      and afferent input from most other hindlimb muscles. Perturbations to hip
      movement were applied either by 1) manual resistance or assistance to swing or by
      2) resistance to hip flexion using a device that blocked hip flexion but allowed
      leg extension. Electromyographic recordings were made from the iliopsoas (IP),
      sartorius, and medial gastrocnemius muscles. When the hip was manually assisted
      into flexion, there was a reduction in hip flexor burst activity. Conversely,
      when hip flexion was manually resisted or mechanically blocked during swing, the
      duration and amplitude of hip flexor activity was increased. We also found some
      specificity in the role of afferents from individual hip flexor muscles in the
      modulation of flexor burst activity. If the IP muscle was detached from its
      insertion, little change in the response to blocking flexion was observed.
      Specific activation of IP afferent fibers by stretching the muscle also did not
      greatly affect flexor activity. On the other hand, if conduction in the sartorius
      nerves was blocked, there was a diminished response to blocking hip flexion. The
      increase in duration of the flexor bursts still occurred, but this increase was
      consistently lower than that observed when the sartorius nerves were intact. From
      these results we propose that during swing, feedback from hip flexor muscle
      afferents, particularly those from the sartorius muscles, enhances flexor
      activity. In addition, if we delayed the onset of flexor activity in the
      contralateral hindlimb, blocking hip flexion often resulted in the prolongation
      of ipsilateral flexor activity for long periods of time, further revealing the
      reinforcing effects of flexor afferent feedback on flexor activity. This effect
      was not seen if conduction in the sartorius nerves was blocked. In conclusion, we
      have found that hip flexor activity during locomotion can be strongly modulated
      by modifying proprioceptive feedback from the hip flexor muscles.

PMID- 11535681
TI  - Responses of auditory cortical neurons to pairs of sounds: correlates of fusion
      and localization.
AB  - When two brief sounds arrive at a listener's ears nearly simultaneously from
      different directions, localization of the sounds is described by "the precedence
      effect." At inter-stimulus delays (ISDs) <5 ms, listeners typically report
      hearing not two sounds but a single fused sound. The reported location of the
      fused image depends on the ISD. At ISDs of 1-4 ms, listeners point near the
      leading source (localization dominance). As the ISD is decreased from 0.8 to 0
      ms, the fused image shifts toward a location midway between the two sources
      (summing localization). When an inter-stimulus level difference (ISLD) is
      imposed, judgements shift toward the more intense source. Spatial hearing,
      including the precedence effect, is thought to depend on the auditory cortex.
      Therefore we tested the hypothesis that the activity of cortical neurons signals
      the perceived location of fused pairs of sounds. We recorded the unit responses
      of cortical neurons in areas A1 and A2 of anesthetized cats. Single broadband
      clicks were presented from various frontal locations. Paired clicks were
      presented with various ISDs and ISLDs from two loudspeakers located 50 degrees to
      the left and right of midline. Units typically responded to single clicks or
      paired clicks with a single burst of spikes. Artificial neural networks were
      trained to recognize the spike patterns elicited by single clicks from various
      locations. The trained networks were then used to identify the locations signaled
      by unit responses to paired clicks. At ISDs of 1-4 ms, unit responses typically
      signaled locations near that of the leading source in agreement with localization
      dominance. Nonetheless the responses generally exhibited a substantial
      undershoot; this finding, too, accorded with psychophysical measurements. As the
      ISD was decreased from ~0.4 to 0 ms, network estimates typically shifted from the
      leading location toward the midline in agreement with summing localization.
      Furthermore a superposed ISLD shifted network estimates toward the more intense
      source, reaching an asymptote at an ISLD of 15-20 dB. To allow quantitative
      comparison of our physiological findings to psychophysical results, we performed
      human psychophysical experiments and made acoustical measurements from the ears
      of cats and humans. After accounting for the difference in head size between cats
      and humans, the responses of cortical units usually agreed with the responses of
      human listeners, although a sizable minority of units defied psychophysical
      expectations.

PMID- 11535682
TI  - Persistent TTX-resistant Na+ current affects resting potential and response to
      depolarization in simulated spinal sensory neurons.
AB  - Small dorsal root ganglion (DRG) neurons, which include nociceptors, express
      multiple voltage-gated sodium currents. In addition to a classical fast
      inactivating tetrodotoxin-sensitive (TTX-S) sodium current, many of these cells
      express a TTX-resistant (TTX-R) sodium current that activates near -70 mV and is
      persistent at negative potentials. To investigate the possible contributions of
      this TTX-R persistent (TTX-RP) current to neuronal excitability, we carried out
      computer simulations using the Neuron program with TTX-S and -RP currents, fit by
      the Hodgkin-Huxley model, that closely matched the currents recorded from small
      DRG neurons. In contrast to fast TTX-S current, which was well fit using a m(3)h
      model, the persistent TTX-R current was not well fit by an m(3)h model and was
      better fit using an mh model. The persistent TTX-R current had a strong influence
      on resting potential, shifting it from -70 to -49.1 mV. Inclusion of an ultra
      slow inactivation gate in the persistent current model reduced the potential
      shift only slightly, to -56.6 mV. The persistent TTX-R current also enhanced the
      response to depolarizing inputs that were subthreshold for spike electrogenesis.
      In addition, the presence of persistent TTX-R current predisposed the cell to
      anode break excitation. These results suggest that, while the persistent TTX-R
      current is not a major contributor to the rapid depolarizing phase of the action
      potential, it contributes to setting the electrogenic properties of small DRG
      neurons by modulating their resting potentials and response to subthreshold
      stimuli.

PMID- 11535683
TI  - GABA(B) and NMDA receptors contribute to spindle-like oscillations in rat
      thalamus in vitro.
AB  - Thalamic slice preparations, in which intrathalamic connectivity between the
      reticular nucleus and relay nuclei is maintained, are capable of sustaining
      rhythmic burst firing activity in rodents and ferret. These in vitro oscillations
      occur spontaneously in the ferret and have frequencies (6-10 Hz) within the range
      of sleep spindles observed in vivo. In the rat, mainly lower frequency (2-4 Hz)
      oscillations, evoked under conditions of low bath [Mg(2+)] and/or GABA(A)
      receptor blockade, have been described. Here we show that faster rhythms in the
      range of 4-9 Hz can be evoked in rat thalamic slices by electrical stimulation of
      the internal capsule and also occur spontaneously. When bath [Mg(2+)] was 2 mM,
      these spindle-like oscillations were most common in a brief developmental time
      window, peaking at postnatal day 12 (P12). The oscillations were almost
      completely blocked by the GABA(A) receptor antagonist picrotoxin, and, in some
      cases, the frequency of oscillations was increased by the GABA(B) receptor
      antagonist CGP-35348. The selective blockade of N-methyl-D-aspartate (NMDA) or
      alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors by the
      antagonists 2-amino-5-phosphonovaleric acid or 1,2,3,4-Tetrahydro-6-nitro-2,3
      dioxo-benzo[f]quinoxaline-7-sulfonamide (NBQX), respectively, significantly
      shortened oscillations but did not completely block them. A combination of the
      two drugs was necessary to abolish oscillatory activity. The barbituate
      pentobarbital, which enhances GABA(A)R responses, initially slowed and
      synchronized oscillations before completely blocking them. When bath [Mg(2+)] was
      reduced from 2 to 0.65 mM, evoked oscillations became more robust and were often
      accompanied by spontaneously arising oscillations. Under these conditions,
      GABA(A) receptor blockade no longer inhibited oscillations, but instead converted
      them into the slow, synchronous rhythms that have been observed in other studies.
      The effects of GABA(B) or NMDA receptor blockade were more pronounced in 0.65 mM
      than in 2 mM external [Mg(2+)]. Thus spindle-like oscillations occur in rat
      thalamic slices in vitro, and we find that, in addition to the previously
      demonstrated contributions of GABA(A) and AMPA receptors to these oscillations,
      NMDA and GABA(B) receptors are also involved. The strong influence of external
      [Mg(2+)] on GABAergic pharmacology and a contribution of NMDA receptors during
      oscillations suggest a link between the excitability of NMDA receptors and the
      activation of GABA(B)R-mediated inhibitory postsynaptic currents.

PMID- 11535684
TI  - Vestibuloocular reflex of the adult flatfish. III. A species-specific reciprocal
      pattern of excitation and inhibition.
AB  - In juvenile flatfish the vestibuloocular reflex (VOR) circuitry that underlies
      compensatory eye movements adapts to a 90 degrees relative displacement of
      vestibular and oculomotor reference frames during metamorphosis. VOR pathways are
      rearranged to allow horizontal canal-activated second-order vestibular neurons in
      adult flatfish to control extraocular motoneurons innervating vertical eye
      muscles. This study describes the anatomy and physiology of identified flatfish
      specific excitatory and inhibitory vestibular pathways. In antidromically
      identified oculomotor and trochlear motoneurons, excitatory postsynaptic
      potentials (EPSPs) were elicited after electrical stimulation of the horizontal
      canal nerve expected to provide excitatory input. Electrotonic depolarizations
      (0.8-0.9 ms) preceded small amplitude (<0.5 mV) chemical EPSPs at 1.2-1.6 ms with
      much larger EPSPs (>1 mV) recorded around 2.5 ms. Stimulation of the opposite
      horizontal canal nerve produced inhibitory postsynaptic potentials (IPSPs) at a
      disynaptic latency of 1.6-1.8 ms that were depolarizing at membrane resting
      potentials around -60 mV. Injection of chloride ions increased IPSP amplitude,
      and current-clamp analysis showed the IPSP equilibrium potential to be near the
      membrane resting potential. Repeated electrical stimulation of either the
      excitatory or inhibitory horizontal canal vestibular nerve greatly increased the
      amplitude of the respective synaptic responses. These observations suggest that
      the large terminal arborizations of each VOR neuron imposes an electrotonic load
      requiring multiple action potentials to maximize synaptic efficacy. GABA
      antibodies labeled axons in the medial longitudinal fasciculus (MLF) some of
      which were hypothesized to originate from horizontal canal-activated inhibitory
      vestibular neurons. GABAergic terminal arborizations were distributed largely on
      the somata and proximal dendrites of oculomotor and trochlear motoneurons. These
      findings suggest that the species-specific horizontal canal inhibitory pathway
      exhibits similar electrophysiological and synaptic transmitter profiles as the
      anterior and posterior canal inhibitory projections to oculomotor and trochlear
      motoneurons. Electron microscopy showed axosomatic and axodendritic synaptic
      endings containing spheroidal synaptic vesicles to establish chemical excitatory
      synaptic contacts characterized by asymmetrical pre/postsynaptic membrane
      specializations as well as gap junctional contacts consistent with electrotonic
      coupling. Another type of axosomatic synaptic ending contained pleiomorphic
      synaptic vesicles forming chemical, presumed inhibitory, synaptic contacts on
      motoneurons that never included gap junctions. Altogether these data provide
      electrophysiological, immunohistochemical, and ultrastructural evidence for
      reciprocal excitatory/inhibitory organization of the novel vestibulooculomotor
      projections in adult flatfish. The appearance of unique second-order vestibular
      neurons linking the horizontal canal to vertical oculomotor neurons suggests that
      reciprocal excitation and inhibition are a fundamental, developmentally linked
      trait of compensatory eye movement circuits in vertebrates.

PMID- 11535686
TI  - Modulation of sensory suppression: implications for receptive field sizes in the
      human visual cortex.
AB  - Neurophysiological studies in monkeys show that when multiple visual stimuli
      appear simultaneously in the visual field, they are not processed independently,
      but rather interact in a mutually suppressive way. This suggests that multiple
      stimuli compete for neural representation. Consistent with this notion, we have
      previously found in humans that functional magnetic resonance imaging (fMRI)
      signals in V1 and ventral extrastriate areas V2, V4, and TEO are smaller for
      simultaneously presented (i.e., competing) stimuli than for the same stimuli
      presented sequentially (i.e., not competing). Here we report that suppressive
      interactions between stimuli are also present in dorsal extrastriate areas V3A
      and MT, and we compare these interactions to those in areas V1 through TEO. To
      exclude the possibility that the differences in responses to simultaneously and
      sequentially presented stimuli were due to differences in the number of transient
      onsets, we tested for suppressive interactions in area V4, in an experiment that
      held constant the number of transient onsets. We found that the fMRI response to
      a stimulus in the upper visual field was suppressed by the presence of nearby
      stimuli in the lower visual field. Further, we excluded the possibility that the
      greater fMRI responses to sequential compared with simultaneous presentations
      were due to exogeneous attentional cueing by having our subjects count T's or L's
      at fixation, an attentionally demanding task. Behavioral testing demonstrated
      that neither condition interfered with performance of the T/L task. Our previous
      findings suggested that suppressive interactions among nearby stimuli in areas V1
      through TEO were scaled to the receptive field (RF) sizes of neurons in those
      areas. Here we tested this idea by parametrically varying the spatial separation
      among stimuli in the display. Display sizes ranged from 2 x 2 degrees to 7 x 7
      degrees and were centered at 5.5 degrees eccentricity. Based on the effects of
      display size on the magnitude of suppressive interactions, we estimated that RF
      sizes at an eccentricity of 5.5 degrees were <2 degrees in V1, 2-4 degrees in V2,
      4-6 degrees in V4, larger than 7 degrees (but still confined to a quadrant) in
      TEO, and larger than 6 degrees (confined to a quadrant) in V3A. These estimates
      of RF sizes in human visual cortex are strikingly similar to those measured in
      physiological mapping studies in the homologous visual areas in monkeys.

PMID- 11535685
TI  - Characterization of the mGluR(1)-mediated electrical and calcium signaling in
      Purkinje cells of mouse cerebellar slices.
AB  - The metabotropic glutamate receptor 1 (mGluR(1)) plays a fundamental role in
      postnatal development and plasticity of ionotropic glutamate receptor-mediated
      synaptic excitation of cerebellar Purkinje cells. Synaptic activation of mGluR(1)
      by brief tetanic stimulation of parallel fibers evokes a slow excitatory
      postsynaptic current and an elevation of intracellular calcium concentration
      ([Ca2+](i)) in Purkinje cells. The mechanism underlying these responses has not
      been identified yet. Here we investigated the responses to synaptic and direct
      activation of mGluR(1) using whole cell patch-clamp recordings in combination
      with microfluorometric measurements of [Ca2+](i) in mouse Purkinje cells.
      Following pharmacological block of ionotropic glutamate receptors, two to six
      stimuli applied to parallel fibers at 100 Hz evoked a slow inward current that
      was associated with an elevation of [Ca2+](i). Both the inward current and the
      rise in [Ca2+](i) increased in size with increasing number of pulses albeit with
      no clear difference between the minimal number of pulses required to evoke these
      responses. Application of the mGluR(1) agonist (S)-3,5-dihydroxyphenylglycine
      (3,5-DHPG) by means of short-lasting (5-100 ms) pressure pulses delivered through
      an agonist-containing pipette positioned over the Purkinje cell dendrite, evoked
      responses resembling the synaptically induced inward current and elevation of
      [Ca2+](i). No increase in [Ca2+](i) was observed with inward currents of
      comparable amplitudes induced by the ionotropic glutamate receptor agonist AMPA.
      The 3,5-DHPG-induced inward current but not the associated increase in [Ca2+](i)
      was depressed when extracellular Na+ was replaced by choline, but, surprisingly,
      both responses were also depressed when bathing the tissue in a low calcium
      (0.125 mM) or calcium-free/EGTA solution. Thapsigargin (10 microM) and
      cyclopiazonic acid (30 microM), inhibitors of sarco-endoplasmic reticulum Ca2+
      ATPase, had little effect on either the inward current or the elevation in
      [Ca2+](i) induced by 3,5-DHPG. Furthermore, the inward current induced by 3,5
      DHPG was neither blocked by 1-[2-(4-methoxyphenyl)-2-[3-(4-methoxyphenyl)propoxy]
      ethyl-1H-imidazole, an inhibitor of store operated calcium influx, nor by
      nimodipine or omega-agatoxin, blockers of voltage-gated calcium channels. These
      electrophysiological and Ca2+-imaging experiments suggest that the mGluR(1)
      mediated inward current, although mainly carried by Na+, involves influx of Ca2+
      from the extracellular space.

PMID- 11535687
TI  - Glutamate receptors form hot spots on apical dendrites of neocortical pyramidal
      neurons.
AB  - Apical dendrites of layer V cortical pyramidal neurons are a major target for
      glutamatergic synaptic inputs from cortical and subcortical brain regions.
      Because innervation from these regions is somewhat laminar along the dendrites,
      knowing the distribution of glutamate receptors on the apical dendrites is of
      prime importance for understanding the function of neural circuits in the
      neocortex. To examine this issue, we used infrared-guided laser stimulation
      combined with whole cell recordings to quantify the spatial distribution of
      glutamate receptors along the apical dendrites of layer V pyramidal neurons.
      Focally applied (<10 microm) flash photolysis of caged glutamate on the soma and
      along the apical dendrite revealed a highly nonuniform distribution of glutamate
      responsivity. Up to four membrane areas (extent 22 microm) of enhanced glutamate
      responsivity (hot spots) were detected on the dendrites with the amplitude and
      integral of glutamate-evoked responses at hot spots being three times larger than
      responses evoked at neighboring sites. We found no association of these
      physiological hot spots with dendritic branch points. It appeared that the larger
      responses evoked at hot spots resulted from an increase in activation of both
      alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D
      aspartate (NMDA) receptors and not a recruitment of voltage-activated sodium or
      calcium conductances. Stimulation of hot spots did, however, facilitate the
      triggering of both Na+ spikes and Ca(2+) spikes, suggesting that hot spots may
      serve as dendritic initiation zones for regenerative spikes.

PMID- 11535688
TI  - Role of NMDA, non-NMDA, and GABA receptors in signal propagation in the amygdala
      formation.
AB  - Although the synaptic physiology of the amygdala has been studied with single
      neuron recordings, the properties of the networks between the various nuclei have
      resisted characterization because of the limitations of field recording in a
      neuronally diffuse structure. We addressed this issue in the rat amygdala complex
      in vitro by using a photodiode array coupled with a voltage-sensitive dye. Low
      intensity single pulse stimulation of the lateral amygdala nucleus produced a
      complex multi-phasic potential. This signal propagated to the basolateral nucleus
      and the amygdalostriatal transition zone but not to the central nucleus. The
      local potential, which depended on both synaptic responses and activation of
      voltage-dependent ion channels, was reduced in amplitude by the non-N-methyl-D
      aspartate (non-NMDA) glutamate receptor antagonist 6,7-dinitroquinoxaline (DNQX)
      and reduced to a lesser extent by the NMDA glutamate receptor antagonist D-2
      amino-5-phosphonovaleric acid (D-APV). We next characterized the less complex
      signals that propagated to more distal regions with or without the addition of
      the GABA receptor antagonist bicuculline (BIC). BIC alone greatly increased the
      signal propagation and permitted activation of previously silent areas within the
      amygdala. DNQX blocked signal propagation to amygdala regions outside of La, even
      in the presence of BIC, whereas D-APV had minimal effects on these distal
      signals. These data represent several novel findings: the characterization of the
      multi-component potential near the site of stimulation, the gating of signal
      propagation within the amygdala by GABAergic inhibition, the critical role of non
      NMDA receptor-mediated depolarization in signal propagation, and the lack of a
      role for NMDA receptors in maintaining propagation.

PMID- 11535689
TI  - Circadian force and EMG activity in hindlimb muscles of rhesus monkeys.
AB  - Continuous intramuscular electromyograms (EMGs) were recorded from the soleus
      (Sol), medial gastrocnemius (MG), tibialis anterior (TA), and vastus lateralis
      (VL) muscles of Rhesus during normal cage activity throughout 24-h periods and
      also during treadmill locomotion. Daily levels of MG tendon force and EMG
      activity were obtained from five monkeys with partial datasets from three other
      animals. Activity levels correlated with the light-dark cycle with peak
      activities in most muscles occurring between 08:00 and 10:00. The lowest levels
      of activity generally occurred between 22:00 and 02:00. Daily EMG integrals
      ranged from 19 mV/s in one TA muscle to 3339 mV/s in one Sol muscle: average
      values were 1245 (Sol), 90 (MG), 65 (TA), and 209 (VL) mV/s. The average Sol EMG
      amplitude per 24-h period was 14 microV, compared with 246 microV for a short
      burst of locomotion. Mean EMG amplitudes for the Sol, MG, TA, and VL during
      active periods were 102, 18, 20, and 33 microV, respectively. EMG amplitudes that
      approximated recruitment of all fibers within a muscle occurred for 5-40 s/day in
      all muscles. The duration of daily activation was greatest in the Sol [151 +/- 45
      (SE) min] and shortest in the TA (61 +/- 19 min). The results show that even a
      "postural" muscle such as the Sol was active for only approximately 9% of the
      day, whereas less active muscles were active for approximately 4% of the day. MG
      tendon forces were generally very low, consistent with the MG EMG data but
      occasionally reached levels close to estimates of the maximum force generating
      potential of the muscle. The Sol and TA activities were mutually exclusive,
      except at very low levels, suggesting very little coactivation of these
      antagonistic muscles. In contrast, the MG activity usually accompanied Sol
      activity suggesting that the MG was rarely used in the absence of Sol activation.
      The results clearly demonstrate a wide range of activation levels among muscles
      of the same animal as well as among different animals during normal cage
      activity.

PMID- 11535690
TI  - Feature analysis of natural sounds in the songbird auditory forebrain.
AB  - Although understanding the processing of natural sounds is an important goal in
      auditory neuroscience, relatively little is known about the neural coding of
      these sounds. Recently we demonstrated that the spectral temporal receptive field
      (STRF), a description of the stimulus-response function of auditory neurons,
      could be derived from responses to arbitrary ensembles of complex sounds
      including vocalizations. In this study, we use this method to investigate the
      auditory processing of natural sounds in the birdsong system. We obtain neural
      responses from several regions of the songbird auditory forebrain to a large
      ensemble of bird songs and use these data to calculate the STRFs, which are the
      best linear model of the spectral-temporal features of sound to which auditory
      neurons respond. We find that these neurons respond to a wide variety of features
      in songs ranging from simple tonal components to more complex spectral-temporal
      structures such as frequency sweeps and multi-peaked frequency stacks. We
      quantify spectral and temporal characteristics of these features by extracting
      several parameters from the STRFs. Moreover, we assess the linearity versus
      nonlinearity of encoding by quantifying the quality of the predictions of the
      neural responses to songs obtained using the STRFs. Our results reveal
      successively complex functional stages of song analysis by neurons in the
      auditory forebrain. When we map the properties of auditory forebrain neurons, as
      characterized by the STRF parameters, onto conventional anatomical subdivisions
      of the auditory forebrain, we find that although some properties are shared
      across different subregions, the distribution of several parameters is suggestive
      of hierarchical processing.

PMID- 11535691
TI  - Quantitative response characteristics of thermoreceptive and nociceptive lamina I
      spinothalamic neurons in the cat.
AB  - The physiological characteristics of antidromically identified lamina I
      spinothalamic (STT) neurons in the lumbosacral spinal cord were examined using
      quantitative thermal and mechanical stimuli in barbiturate-anesthetized cats.
      Cells belonging to the three main recognized classes were included based on
      categorization with natural cutaneous stimulation of the hindpaw: nociceptive
      specific (NS), polymodal nociceptive (HPC), or thermoreceptive-specific (COOL)
      cells. The mean central conduction latencies of these classes differed
      significantly; NS = 130.8 +/- 55.5 (SD) ms (n = 100), HPC = 72.1 +/- 28.0 ms (n =
      128), and COOL = 58.6 +/- 25.3 ms (n = 136), which correspond to conduction
      velocities of 2.5, 4.6, and 5.6 m/s. Based on recordings made prior to any
      noxious stimulation, the mean spontaneous discharge rates of these classes also
      differed: NS = 0.5 +/- 0.7 imp/s (n = 47), HPC = 0.9 +/- 0.7 imp/s (n = 59), and
      COOL = 3.3 +/- 2.6 imp/s (n = 107). Standard, quantitative, thermal stimulus
      sequences applied with a Peltier thermode were used to characterize the stimulus
      response functions of 76 COOL cells, 47 HPC cells, and 37 NS cells. The COOL
      cells showed a very linear output from 34 degrees C down to approximately 15
      degrees C and a maintained plateau thereafter. The HPC cells showed a fairly
      linear but accelerating response to cold below a median threshold of
      approximately 24 degrees C and down to 9 degrees C (measured at the skin-thermode
      interface with a thermode temperature of 2 degrees C). The HPC cells and the NS
      cells both showed rapidly increasing, sigmoidal response functions to noxious
      heat with a fairly linear response between 45 and 53 degrees C, but they had
      significantly different thresholds; half of the HPC cells were activated at ~45.5
      degrees C and half of the NS cells at approximately 43 degrees C. The 20 HPC
      lamina I STT cells and 10 NS cells tested with quantitative pinch stimuli showed
      fairly linear responses above a threshold of approximately 130 g/mm(2) for HPC
      cells and a threshold of approximately 100 g/mm(2) for NS cells. All of these
      response functions compare well (across species) with the available data on the
      characteristics of thermoreceptive and nociceptive primary afferent fibers and
      the appropriate psychophysics in humans. Together these results support the
      concept that these classes of lamina I STT cells provide discrete sensory
      channels for the sensations of temperature and pain.

PMID- 11535692
TI  - Mechanisms that initiate spontaneous network activity in the developing chick
      spinal cord.
AB  - Many developing networks exhibit a transient period of spontaneous activity that
      is believed to be important developmentally. Here we investigate the initiation
      of spontaneous episodes of rhythmic activity in the embryonic chick spinal cord.
      These episodes recur regularly and are separated by quiescent intervals of many
      minutes. We examined the role of motoneurons and their intraspinal synaptic
      targets (R-interneurons) in the initiation of these episodes. During the latter
      part of the inter-episode interval, we recorded spontaneous, transient ventral
      root depolarizations that were accompanied by small, spatially diffuse
      fluorescent signals from interneurons retrogradely labeled with a calcium
      sensitive dye. A transient often could be resolved at episode onset and was
      accompanied by an intense pre-episode (approximately 500 ms) motoneuronal
      discharge (particularly in adductor and sartorius) but not by interneuronal
      discharge monitored from the ventrolateral funiculus (VLF). An important role for
      this pre-episode motoneuron discharge was suggested by the finding that
      electrical stimulation of motor axons, sufficient to activate R-interneurons,
      could trigger episodes prematurely. This effect was mediated through activation
      of R-interneurons because it was prevented by pharmacological blockade of either
      the cholinergic motoneuronal inputs to R-interneurons or the GABAergic outputs
      from R-interneurons to other interneurons. Whole-cell recording from R
      interneurons and imaging of calcium dye-labeled interneurons established that R
      interneuron cell bodies were located dorsomedial to the lateral motor column (R
      interneuron region). This region became active before other labeled interneurons
      when an episode was triggered by motor axon stimulation. At the beginning of a
      spontaneous episode, whole-cell recordings revealed that R-interneurons fired a
      high-frequency burst of spikes and optical recordings demonstrated that the R
      interneuron region became active before other labeled interneurons. In the
      presence of cholinergic blockade, however, episode initiation slowed and the
      inter-episode interval lengthened. In addition, optical activity recorded from
      the R-interneuron region no longer led that of other labeled interneurons.
      Instead the initial activity occurred bilaterally in the region medial to the
      motor column and encompassing the central canal. These findings are consistent
      with the hypothesis that transient depolarizations and firing in motoneurons,
      originating from random fluctuations of interneuronal synaptic activity, activate
      R-interneurons, which then trigger the recruitment of the rest of the spinal
      interneuronal network. This unusual function for R-interneurons is likely to
      arise because the output of these interneurons is functionally excitatory during
      development.

PMID- 11535693
TI  - Differential coding of pain intensity in the human primary and secondary
      somatosensory cortex.
AB  - The primary (SI) and secondary (SII) somatosensory cortices have been shown to
      participate in human pain processing. However, in humans it is unclear how SI and
      SII contribute to the encoding of nociceptive stimulus intensity. Using
      magnetoencephalography (MEG) we recorded responses in SI and SII in eight healthy
      humans to four different intensities of selectively nociceptive laser stimuli
      delivered to the dorsum of the right hand. Subjects' pain ratings correlated
      highly with the applied stimulus intensity. Activation of contralateral SI and
      bilateral SII showed a significant positive correlation with stimulus intensity.
      However, the type of dependence on stimulus intensity was different for SI and
      SII. The relation between SI activity and stimulus intensity resembled an
      exponential function and matched closely the subjects' pain ratings. In contrast,
      SII activity showed an S-shaped function with a sharp increase in amplitude only
      at a stimulus intensity well above pain threshold. The activation pattern of SI
      suggests participation of SI in the discriminative perception of pain intensity.
      In contrast, the all-or-none-like activation pattern of SII points against a
      significant contribution of SII to the sensory-discriminative aspects of pain
      perception. Instead, SII may subserve recognition of the noxious nature and
      attention toward painful stimuli.

PMID- 11535694
TI  - Spike coding in pyramidal cells of the piriform cortex of rat.
AB  - The study of cortical oscillations has undergone a renaissance in recent years
      because of their presumed role in cognitive function. Of particular interest are
      frequencies in the gamma (30-100 Hz) and theta (3-12 Hz) ranges. In this paper,
      we use spike coding techniques and in vitro whole cell recording to assess the
      ability of individual pyramidal cells of the piriform cortex to code inputs
      occurring in these frequencies. The results suggest that the spike trains of
      individual neurons are much better at representing frequencies in the theta range
      than those in the gamma range.

PMID- 11535695
TI  - Origin of colorectal cancers in hyperplastic polyps and serrated adenomas:
      another truism bites the dust.

PMID- 11535696
TI  - Debate on the link between SV40 and human cancer continues.

PMID- 11535698
TI  - Recent studies bring risks, benefits of hormone replacement therapy under
      scrutiny.

PMID- 11535699
TI  - Two British cancer charities may join forces.

PMID- 11535701
TI  - Scottish Health Executive revamps cancer care.

PMID- 11535703
TI  - Why most randomized phase II cervical cancer chemoprevention trials are
      uninformative: lessons for the future.

PMID- 11535704
TI  - Risk-reduction mastectomy: clinical issues and research needs.
AB  - Risk-reduction mastectomy (RRM), also known as bilateral prophylactic mastectomy,
      is a controversial clinical option for women who are at increased risk of breast
      cancer. High-risk women, including women with a strong family history of breast
      cancer and BRCA1/2 mutation carriers, have several clinical options: risk
      reduction surgery (bilateral mastectomy and bilateral oophorectomy), surveillance
      (mammography, clinical breast examination, and breast self-examination), and
      chemoprevention (tamoxifen). We review research in a number of areas central to
      our understanding of RRM, including recent data on 1) the effectiveness of RRM in
      reducing breast cancer risk, 2) the perception of RRM among women at increased
      risk and health-care providers, 3) the decision-making process for follow-up care
      of women at high risk, and 4) satisfaction and psychological status after
      surgery. We suggest areas of future research to better guide high-risk women and
      their health-care providers in the decision-making process.

PMID- 11535705
TI  - Sporadic colorectal cancers with microsatellite instability and their possible
      origin in hyperplastic polyps and serrated adenomas.
AB  - BACKGROUND: Microsatellite instability (MSI) is seen in 10%-15% of sporadic
      colorectal cancers mostly in the right colon, but the precursors of cancers with
      MSI remain unknown. We examined whether sporadic cancers with MSI arise from pre
      existing benign proliferative lesions (such as hyperplastic polyps or serrated
      adenomas [together denoted as "serrated polyps"]). METHODS: The frequency of
      benign epithelial lesions (serrated polyps and conventional adenomas) was
      determined by histologic review of resection specimens from individuals (n = 29)
      with sporadic colorectal cancer with MSI and from a matched control group (n =
      29) with cancer showing microsatellite stability (MSS). MSI status, expression of
      mismatch repair enzyme (product of the human mut-L homologue 1 [hMLH1] gene), and
      hMLH1 gene promoter methylation in the benign lesions were determined. Data were
      analyzed by the chi-square test, by Wilcoxon's rank-sum test, and by conditional
      logistic regression as appropriate, and a two-sided probability less than.05 was
      considered to be statistically significant. RESULTS: Individuals with cancers
      showing MSI were more likely to harbor at least one serrated polyp than
      individuals with cancers showing MSS (odds ratio = 4.0; 95% confidence interval =
      1.1 to 14.2; P =.03), but the frequency of conventional adenomas was the same in
      both groups (P =.52, Mann-Whitney test). Loss of hMLH1 protein expression was
      seen in lesions from 10 of 13 patients with MSI, but no loss was seen in lesions
      from four patients with MSS (P =.02, Fisher's exact test). Loss of hMLH1 protein
      expression was associated with MSI in assessable lesions. The hMLH1 promoter was
      methylated in all assessable serrated polyps from patients with cancers showing
      MSI but in none of the lesions from patients with MSS cancers. CONCLUSIONS: Some
      right-sided hyperplastic polyps may give rise to sporadic colorectal carcinomas
      with MSI. Methylation of the hMLH1 gene promoter within neoplastic cell
      subpopulations may be a critical step in the progression to carcinoma. The
      frequency with which benign lesions progress to cancer with MSI is unknown.

PMID- 11535706
TI  - Use of the probasin promoter ARR2PB to express Bax in androgen receptor-positive
      prostate cancer cells.
AB  - BACKGROUND: Adenovirus-mediated overexpression of the apoptosis-inducing protein
      Bax can induce apoptosis in prostate cancer cell lines. Constitutive
      overexpression of Bax could result in unwanted apoptosis in every site of
      accidental Bax accumulation in vivo. Therefore, we developed an adenoviral
      construct (Av-ARR2PB-Bax) in which the probasin promoter, modified to contain two
      androgen response elements, drives Bax expression. This promoter would be
      expected to limit expression of Bax to cells expressing the androgen receptor.
      METHODS: A variety of androgen receptor (AR)-positive and -negative cell lines of
      prostatic or nonprostatic origin were infected with Av-ARR2PB-Bax or a control
      virus, Av-ARR2PB-CAT, in which the same promoter drives expression of the
      chloramphenicol acetyl transferase-reporter gene. Bax expression and apoptosis in
      vitro were assessed by western blot analysis. Tumor size and apoptosis in vivo
      were assessed after four weekly injections of Av-ARR2PB-Bax or Av-ARR2PB-CAT into
      subcutaneous LNCaP xenografts growing in uncastrated male mice. All statistical
      tests were two-sided. RESULTS: Bax was overexpressed in an androgen-dependent way
      in AR-positive cell lines of prostatic origin but not in AR-positive cells of
      nonprostatic origin or in AR-negative cell lines of either prostatic or
      nonprostatic origin. The androgen dihydrotestosterone activated apoptosis in
      LNCaP cells infected with Av-ARR2PB-Bax but not in those infected with Av-ARR2PB
      CAT. Av-ARR2PB-Bax-injected LNCaP xenograft tumors decreased in tumor size from
      34.1 mm3 (95% confidence interval [CI] = 25.1 mm3 to 43.1 mm3) to 24.6 mm3 (95%
      CI = -2.5 mm3 to 51.7 mm3), but the difference was not statistically significant
      (P =.5). Tumors injected with Av-ARR2PB-CAT increased in size, from 28.9 mm3 (95%
      CI = 12.7 mm3 to 45.1 mm3) to 206 mm3 (95% CI = 122 mm3 to 290 mm3) (P =.002) and
      contained statistically significant more apoptotic cells (23.3% [95% CI = 21.1%
      to 25.6%] versus 9.5% [95% CI = 8.0% to 11.1]) (P<.001). CONCLUSIONS: Av-ARR2PB
      Bax induces androgen-dependent therapeutic apoptosis in vitro and in vivo by
      activating apoptosis in AR-positive cells derived specifically from prostatic
      epithelium and does not affect nonprostatic cells.

PMID- 11535707
TI  - Asian-American variants of human papillomavirus 16 and risk for cervical cancer:
      a case-control study.
AB  - BACKGROUND: Human papillomavirus 16 (HPV16) has a number of variants, each with a
      different geographic distribution and some that are associated more often with
      invasive neoplasias. We investigated whether the high incidence of cervical
      cancer in Mexico (50 cases per 100 000 women) may be associated with a high
      prevalence of oncogenic HPV16 variants. METHODS: Cervical samples were collected
      from 181 case patients with cervical cancer and from 181 age-matched control
      subjects, all from Mexico City. HPV16 was detected with an E6/E7 gene-specific
      polymerase chain reaction, and variant HPV classes and subclasses were identified
      by sequencing regions of the E6 and L1/MY genes. Clinical data and data on tumor
      characteristics were also collected. All statistical tests were two-sided.
      RESULTS: HPV16 was detected in cervical scrapes from 50.8% (92 of 181) of case
      patients and from 11% (20 of 181) of control subjects. All HPV16-positive
      samples, except one, contained European (E) or Asian-American (AA) variants. AA
      and E variants were found statistically significantly more often in case patients
      (AA = 23.2% [42 of 181]; E = 27.1% [49 of 181]) than in control subjects (AA =
      1.1% [two of 181]; E = 10% [18 of 181]) (P<.001 for case versus control subjects
      for either E or AA variants, chi2 test). However, the frequency of AA variants
      was 21 times higher in cancer patients than in control subjects, whereas that
      ratio for E variants was only 2.7 (P =.006, chi2 test). The odds ratio (OR) for
      cervical cancer associated with AA variants (OR = 27.0; 95% confidence interval
      [CI] = 6.4 to 113.7) was higher than that associated with E variants (OR = 3.4;
      95% CI = 1.9 to 6.0). AA-positive case patients (46.2 +/- 12.5 years [mean +/-
      standard deviation]) were 7.7 years younger than E-positive case patients (53.9
      +/- 12.2 years) (P =.004, Student's t test). AA variants were associated with
      squamous cell carcinomas and adenocarcinomas, but E variants were associated with
      only squamous cell carcinomas (P =.014, Fisher's exact test). CONCLUSIONS: The
      high frequency of HPV16 AA variants, which appear to be more oncogenic than E
      variants, might contribute to the high incidence of cervical cancer in Mexico.

PMID- 11535708
TI  - Milk intake, circulating levels of insulin-like growth factor-I, and risk of
      colorectal cancer in men.
AB  - BACKGROUND: Milk and dietary calcium may have antiproliferative effects against
      colorectal cancer, but milk intake also raises serum levels of insulin-like
      growth factor-I (IGF-I). A high ratio of IGF-I to IGF-binding protein-3 (IGFBP-3)
      has been linked to an increased risk of colorectal cancer. METHODS: In a case
      control study nested in the Physicians' Health Study, plasma samples were
      collected from the period 1982 through 1983 from 14 916 men, aged 40-84 years,
      who also answered dietary questionnaires. Circulating levels of IGF-I and IGFBP-3
      were assayed among 193 men who developed colorectal cancer during 13 years of
      follow-up and 318 age- and smoking-matched cancer-free control men. Conditional
      logistic regression was used to assess relative risks (RRs) of colorectal cancer
      for tertiles of IGF-I/IGFBP-3 and dietary factors. Statistical tests were two
      sided. RESULTS: Overall, there was a moderate but statistically nonsignificant
      inverse association between intake of low-fat milk or calcium from dairy food and
      colorectal cancer risk. Intake of dairy food (especially low-fat milk) was also
      positively and moderately associated with plasma levels of IGF-I, IGFBP-3, and
      IGF-I/IGFBP-3 among control men. We observed a statistically significant
      interaction between low-fat milk intake and IGF-I/IGFBP-3 in association with
      risk of colorectal cancer (P(interaction) =.03). Nondrinkers with IGF-I/IGFBP-3
      in the highest tertile had a threefold higher risk than nondrinkers with IGF
      I/IGFBP-3 in the lowest tertile (RR = 3.05; 95% confidence interval [CI] = 1.29
      to 7.24), but no such increase was seen among frequent low-fat milk drinkers (RR
      = 1.05; 95% CI = 0.41 to 2.69). Conversely, among men with high IGF-I/IGFBP-3,
      frequent low-fat milk drinkers had a 60% lower risk (95% CI = 0.17 to 0.87;
      P(trend) =.02) than nondrinkers. CONCLUSION: Intake of dairy products was
      associated with a modest increase in circulating IGF-I levels, but intake of low
      fat milk was associated with lower risk of colorectal cancer, particularly among
      individuals with high IGF-I/IGFBP-3. This subpopulation, which is at increased
      risk of colorectal cancer, might benefit the most from specific dietary
      intervention.

PMID- 11535709
TI  - Transcriptional response to hypoxia in human tumors.
AB  - BACKGROUND: The presence of hypoxic regions within solid tumors is associated
      with a more malignant tumor phenotype and worse prognosis. To obtain a blood
      supply and protect against cellular damage and death, oxygen-deprived cells in
      tumors alter gene expression, resulting in resistance to therapy. To investigate
      the mechanisms by which cancer cells adapt to hypoxia, we looked for novel
      hypoxia-induced genes. METHODS: The transcriptional response to hypoxia in human
      glioblastoma cells was quantified with the use of serial analysis of gene
      expression. The time course of gene expression in response to hypoxia in a panel
      of various human tumor cell lines was measured by real-time polymerase chain
      reaction. Hypoxic regions of human carcinomas were chemically marked with
      pimonidazole. Immunohistochemistry and in situ hybridization were used to examine
      gene expression in the tumor's hypoxic regions. RESULTS: From the 24 504 unique
      transcripts expressed, 10 new hypoxia-regulated genes were detected-all induced,
      to a greater extent than vascular endothelial growth factor, a hypoxia-induced
      mitogen that promotes blood vessel growth. These genes also responded to hypoxia
      in breast and colon cancer cells and were activated by hypoxia-inducible factor
      1, a key regulator of hypoxic responses. In tumors, gene expression was limited
      to hypoxic regions. Induced genes included hexabrachion (an extracellular matrix
      glycoprotein), stanniocalcin 1 (a calcium homeostasis protein), and an
      angiopoietin-related gene. CONCLUSIONS: We have identified the genes that are
      transcriptionally activated within hypoxic malignant cells, a crucial first step
      in understanding the complex interactions driving hypoxia response. Within our
      catalogue of hypoxia-responsive genes are novel candidates for hypoxia-driven
      angiogenesis.

PMID- 11535710
TI  - Relationship of distance from a radiotherapy facility and initial breast cancer
      treatment.

PMID- 11535711
TI  - Re: A novel fusion gene, SYT-SSX4, in synovial sarcoma.

PMID- 11535713
TI  - Re: Cervical carcinoma and human papillomavirus: on the road to preventing a
      major human cancer.

PMID- 11535714
TI  - Subcellular micromolecular pharmacotherapy using computer-assisted microarray
      analysis.

PMID- 11535716
TI  - Hyperactivity of 99mTc-HMPAO within 6 hours in patients with acute ischemic
      stroke.
AB  - Intraarterial thrombolytic therapy has been used recently for treatment of acute
      ischemic stroke within 6 h after onset. Although hypoactivity of 99mTc
      hexamethylpropyleneamine oxime (HMPAO) in stroke has been well documented,
      hyperactivity of HMPAO has not been evaluated in sufficient detail. The purpose
      of this study was to evaluate the incidence and clinical importance of
      hyperactivity of HMPAO in management of patients with acute ischemic stroke.
      METHODS: We retrospectively investigated HMPAO SPECT in 90 patients with acute
      ischemic stroke within 6 h after onset. The lesion-to-contralateral radioactivity
      ratios (L/Cs) were calculated on the SPECT images before treatment and were
      compared with the imaging results of CT or MRI (or both). RESULTS: Hyperactivity
      of HMPAO, accompanied by surrounding hypoactivity, was observed in 6 of 90
      patients (7%) within 6 h after onset. The L/Cs ranged from 1.17 to 2.95. Two
      patients showed hyperactivity in the cortex and the other 4 patients showed
      hyperactivity in the basal ganglia. Angiography confirmed spontaneous
      recanalization of occluded vessels in accordance with the area of hyperactivity.
      In both patients with cortical hyperactivity, cerebral infarctions were revealed
      on follow-up CT; in 1 patient, hemorrhagic transformation developed after
      intraarterial thrombolytic therapy. In 3 of the 4 patients with hyperactivity in
      the basal ganglia, follow-up CT showed no infarction in the surrounding
      hypoperfused cortex (selective intraarterial thrombolytic therapy was performed
      on 2 patients), although various degrees of infarction were observed in the basal
      ganglia. Obvious infarctions developed in the basal ganglia and the cortex of the
      other patient. CONCLUSION: Hyperactivity of HMPAO could be seen in the basal
      ganglia and the cortex within 6 h after onset, reflecting spontaneous
      recanalization. The areas of hyperactivity may develop infarctions, whereas the
      accompanying areas of hypoactivity could be rescued by selective intraarterial
      thrombolytic therapy.

PMID- 11535717
TI  - Evaluation of early-stage Parkinson's disease with 99mTc-TRODAT-1 imaging.
AB  - Parkinson's disease is a progressive neurodegenerative disorder characterized by
      a selective loss of dopamine in the striatum. Problems remain in the accurate
      diagnosis of Parkinson's disease. A 99mTc-labeled tropane derivative that binds
      to dopamine transporter with high selectivity is [2-[[2-[[[3-(4-chlorophenyl)-8
      methyl-8-azabicyclo[3,2,1]oct-2-yl]methyl](2
      mercaptoethyl)amino]ethyl]amino]ethanethiolato(3-)-N2,N2',S2,S2']oxo-[1R-(exo
      exo)] (TRODAT-1). The purpose of this study was to investigate the potential
      usefulness of 99mTc-TRODAT-1 imaging in the evaluation of patients with early
      stage Parkinson's disease. METHODS: Thirty-four patients with early-stage
      idiopathic Parkinson's disease were recruited. For all patients, the Parkinson's
      disease was stage 2 or less as assessed by the Hoehn and Yahr scale. Seventeen
      age-matched healthy volunteers (8 men, 9 women) served as controls. 99mTc-TRODAT
      1 was prepared from a lyophilized kit. Brain SPECT imaging was performed between
      165 and 195 min after injection, using a double-head camera equipped with fanbeam
      collimators. Specific uptake in the striatum and its subregions, including the
      putamen and caudate nucleus, was calculated and compared with that of the other
      sides and of healthy volunteers. RESULTS: A continuous reduction in specific
      striatal uptake of 99mTc-TRODAT-1 with increasing disease severity was found in
      Parkinson's disease patients (control vs. stage I vs. stage II, 1.98 vs. 1.62 vs.
      1.22, respectively, P < 0.01). The changes were magnified by measurement of
      specific putaminal uptake (control vs. stage I vs. stage II, 1.81 vs. 1.27 vs.
      0.94, respectively, P < 0.01). The mean values of specific putaminal uptake
      contralateral to the more affected limbs were significantly decreased compared
      with the ipsilateral sides in both stage I and stage II groups (1.02 vs. 1.49 for
      stage I and 0.73 vs. 1.14 for stage II, P < 0.01). Moreover, a significant loss
      of putaminal uptake ipsilateral to the symptoms was found in the stage I group
      compared with the healthy volunteers (1.49 vs. 1.81, P < 0.01). The difference
      became greater when the posterior putaminal uptakes were compared. No remarkable
      adverse reactions were found in either healthy volunteers or Parkinson's disease
      patients during or after imaging. CONCLUSION: For clinical practice, 99mTc-TRODAT
      1 may serve as a useful imaging agent for the early detection of Parkinson's
      disease.

PMID- 11535718
TI  - 111In-DOTA-lanreotide scintigraphy in patients with tumors of the lung.
AB  - Imaging with radiolabeled somatostatin (SST) analogs has recently been
      established for the localization of various human SST receptor (hsstr)-positive
      tumors, including neuroendocrine tumors, lymphomas, and non-small cell lung
      cancer (NSCLC). METHODS: 111In-1,4,7,10-tetraazacyclododecane-N,N',N",N"'
      tetraacetic acid-lanreotide (DOTA-LAN) scintigraphy (150 MBq; 7 nmol per patient)
      was performed on 47 patients (28 patients with primary tumors, 19 patients with
      lung metastases from other tumors) to evaluate the tumor binding in patients with
      histologically confirmed lung cancer. A group of 27 tumor patients without
      documented lung lesions served as the control group. Early and delayed planar and
      SPECT images were acquired. Whole-body scintigraphy was performed at 0.5, 4-6,
      24, and 48 h after injection for tumor dose estimation. In addition, hsstr
      subtype expression and radioligand binding characteristics were studied in vitro
      using lung tumor samples (n = 15). RESULTS: 111In-DOTA-LAN indicated the primary
      lung tumor in 16 of 16 NSCLC patients. Lymph node metastases were visualized in 6
      of 6 NSCLC patients, and bone metastases were seen in 3 of 3 NSCLC patients.
      111In-DOTA-LAN scintigraphy indicated lung carcinoid in 5 of 5 patients and small
      cell lung cancer lesions in 6 of 6 patients. Multiple lung metastases were shown
      in all 6 patients with non-Hodgkin's lymphoma and in the 1 patient with Hodgkin's
      disease, 5 of 5 colorectal adenocarcinoma patients, 4 of 4 carcinoid patients, 2
      of 2 neuroendocrine carcinoma (NEC) patients, and 1 of 1 angiosarcoma patient.
      Pulmonary tumor sites not indicated by CT or MRI were visualized in 6 of 47 tumor
      patients (i.e., 13%; lung metastases in 1 carcinoid patient and 1 NEC patient,
      lymph node metastases in 1 carcinoid patient and 2 NSCLC patients, bone
      metastases in 1 carcinoid patient). The estimated lung tumor dose ranged between
      0.2 and 5 mGy/MBq. Focal lung uptake of 111In-DOTA-LAN was not observed in any of
      the 27 control patients. In vitro binding studies indicated high-affinity binding
      sites for 111In-DOTA-LAN in NSCLC samples (dissociation constants, 0.5 and 4
      nmol/L) with predominant expression of hsstr4. CONCLUSION: 111In-DOTA-LAN yields
      high tumor binding for various human lung tumors. Consecutively, radiopeptide
      therapy may offer a potential new treatment alternative for some lung tumor
      patients.

PMID- 11535719
TI  - Noise reduction in oncology FDG PET images by iterative reconstruction: a
      quantitative assessment.
AB  - Tumor detection depends on the contrast between tumor activity and background
      activity and on the image noise in these 2 regions. The lower the image noise,
      the easier the tumor detection. Tumor activity contrast is determined by
      physiology. Noise, however, is affected by many factors, including the choice of
      reconstruction algorithm. Previous simulation and phantom measurements indicated
      that the ordered-subset expectation maximization (OSEM) algorithm may produce
      less noisy images than does the usual filtered backprojection (FBP) method, at
      equivalent resolution. To see if this prediction would hold in actual clinical
      situations, we quantified noise in clinical images reconstructed with both OSEM
      and FBP. METHODS: Three patients (2 with colon cancer, 1 with breast cancer) were
      imaged with FDG PET using a "gated replicate" technique that permitted accurate
      measurement of noise at each pixel. Each static image was acquired as a gated
      image sequence, using a pulse generator with a 1-s period, yielding 40 replicate
      images over the 10- to 15-min imaging time. The images were or were not
      precorrected for attenuation and were reconstructed with both FBP and OSEM at
      comparable resolution. From these data, images of pixel mean, SD, and signal-to
      noise ratio (S/N) could be produced, reflecting only noise caused by the
      statistical fluctuations in the emission process. RESULTS: Noise did not vary
      greatly over each FBP image, even when image intensity varied greatly from one
      region to the next, causing S/N to be worse in low-activity regions than in high
      activity regions. In contrast, OSEM had high noise in hot regions and low noise
      in cold regions. OSEM had a much better S/N than did FBP in cold regions of the
      image, such as the lungs (in the attenuation-corrected images), where
      improvements in S/N averaged 160%. Improvements with OSEM were less dramatic in
      hotter areas such as the liver (averaging 25% improvement in the attenuation
      corrected images). In very hot tumors, FBP actually produced higher S/Ns than did
      OSEM. CONCLUSION: We conclude that OSEM reconstruction can significantly reduce
      image noise, especially in relatively low-count regions. OSEM reconstruction
      failed to improve S/N in very hot tumors, in which S/N may already be adequate
      for tumor detection.

PMID- 11535720
TI  - Metabolite production in patients with lymphoma after radiometal-labeled antibody
      administration.
AB  - Radiometal-labeled monoclonal antibodies are retained longer in tumors than
      iodinated antibodies, leading to their increased use for radioimmunotherapy.
      Dissociation of radioiodine from the antibody during metabolism has been
      documented. We now report metabolites in the plasma of lymphoma patients given
      111In- and 90Y-2-iminothiolane-2-[p-(bromoacetamido)benzyl]-1,4,7,10
      tetraazacyclododecane-N,N',N",N"'-tetraacetic acid-Lym-1 (111In/90Y-2IT-BAD-Lym
      1). METHODS: Nineteen patients with non-Hodgkin's lymphoma (NHL) received 111In-
      and 90Y-2IT-BAD-Lym-1; 111In was used as a surrogate tracer for 90Y, which emits
      no gamma-photon. Plasma was obtained up to 7 d and analyzed by high-performance
      liquid chromatography to determine the fraction of radiolabel associated with
      monomeric antibody, metabolites, and complexed antibody. Planar images of
      conjugate views were acquired up to 7 d and used to quantitate 111In in organs
      and tumors. RESULTS: Metabolites and complexes were observed in the plasma of
      every patient who received 111In-2IT-BAD-Lym-1. At 3 d, the mean percentages of
      111In in the patients' plasma in monomeric, metabolite, and complexed forms were
      54%, 36%, and 10%, respectively. Metabolites of 90Y-2IT-BAD-Lym-1 were formed to
      a similar extent. In comparison, in groups of breast and prostate cancer patients
      who received the radioimmunoconjugate 111In-2IT-BAD-m170, 91% and 94% of 111In in
      the patients' plasma were in monomeric form, respectively. Metabolites and
      complexes of 111In-2IT-BAD-Lym-1 contributed a mean 10% of the total area under
      the time-activity curve (AUC) for blood. Little formation of metabolites and
      complexes occurred in vitro in NHL patient or volunteer plasma or in Raji cell
      culture. The clinical and in vitro data supported the processing of 111In/90Y-2IT
      BAD-Lym-1 in the hepatocytes as the dominant mechanism for the production of
      metabolites. CONCLUSION: Metabolites of 111In/90Y-2IT-BAD-Lym-1 accounted for 10%
      of blood AUC in patients. The therapeutic index was adversely affected by
      metabolism of 111In/90Y-2IT-BAD-Lym-1 to the extent that the tumor specificity of
      the radioactive metabolites was lost.

PMID- 11535721
TI  - Impact of whole-body 18F-FDG PET on staging and managing patients with breast
      cancer: the referring physician's perspective.
AB  - FDG PET has emerged as an important clinical imaging modality for diagnosing and
      staging cancer. However, the impact of FDG PET on staging and managing patients
      with breast cancer from the referring physician's point of view is unknown.
      METHODS: The referring physicians of 160 breast cancer patients received
      standardized questionnaires inquiring if and how PET findings altered their
      patient's stage and their clinical management decisions. Management changes were
      classified as intermodality if the change was from one modality to another (e.g.,
      medical to surgical, surgical to radiation, medical to no treatment, and vice
      versa) or as intramodality if the change was within the same modality (e.g.,
      altered medical or radiotherapy approach). RESULTS: Fifty of the 160 surveys were
      completed (31% response rate). PET changed the clinical stage in 36% of patients
      (28% upstaged, 8% downstaged) and resulted in intermodality changes in 28% of
      patients and intramodality changes in 30% of patients. CONCLUSION: The results of
      this prospective survey show that FDG PET has a major impact on the management of
      breast cancer patients, influencing both clinical stage and management in more
      than 30% of patients.

PMID- 11535722
TI  - Molecular biologic and scintigraphic analyses of somatostatin receptor-negative
      meningiomas.
AB  - Somatostatin receptor scintigraphy (SRS) using 111In-octreotide has proven useful
      in the preoperative discrimination of expansive central nervous system lesions.
      Meningiomas, generally expressing human somatostatin receptor (hsst) on their
      surface, were detected with a sensitivity of about 100%. This finding was
      associated with the assumption that meningiomas lack an intact blood-brain
      barrier. However, this exclusion procedure became questionable when
      histologically proven meningiomas in which SRS was negative were reported.
      Therefore, the aim of this study was to discover why these meningiomas gave
      negative SRS results. METHODS: Before surgery, 46 patients with 47 meningiomas
      underwent standard MRI and SRS. Thirty-four of these patients with 35 tumors were
      also examined by 99mTc-diethylenetriaminepentaacetic acid (DTPA) brain
      scintigraphy. After surgical resection, hsst subtype 2 (hsst2) messenger RNA
      (mRNA) expression of 4 SRS-positive and 4 SRS-negative meningiomas was estimated
      semiquantitatively by reverse transcriptase polymerase chain reaction (RT-PCR).
      Translation of hsst2 mRNA into receptor proteins was proven immunocytochemically
      on the surface of 1 SRS-positive and 1 SRS-negative meningioma. Tumor specimens
      used for RNA extraction and RT-PCR and cultivated cells used for hsst2
      immunostaining were tested for their meningioma nature by immunochemistry.
      RESULTS: SRS yielded positive results in 39 meningiomas with a tumor volume of
      24.1 +/- 32.8 mL and negative results in 8 meningiomas with a volume of 3.9 +/-
      6.5 mL. 99mTc-DTPA scintigraphy visualized 24 of 35 meningiomas. SRS was positive
      in all of them. In contrast, 11 meningiomas were (99mTc-DTPA negative. In these
      meningiomas, SRS was negative in 5 cases (5.4 +/- 8.1 mL), whereas the remaining
      6 were positive (4.6 +/- 4.5 mL). None of the meningiomas was 99mTc-DTPA positive
      and SRS negative. RT-PCR revealed no significant difference of hsst2 mRNA
      expression between SRS-positive and SRS-negative meningiomas but showed varied
      expression among all meningiomas regardless of SRS results. Furthermore, hsst2
      proteins were visualized immunocytochemically on the surface of cultivated cells
      of SRS-positive and SRS-negative meningiomas. CONCLUSION: SRS-negative
      meningiomas do express hsst2; thus, in these meningiomas SRS is false-negative.
      Because an insufficient sensitivity was excluded, 99mTc-DTPA scintigraphy
      identified a permeability barrier in SRS-negative meningiomas that explains their
      false-negative SRS results. SRS-negative meningiomas most likely meet the
      function of their tissue of origin (the meninges) to develop more-or-less intact
      permeability barriers.

PMID- 11535723
TI  - Total and partial cardiac sympathetic denervation after surgical repair of
      ascending aortic aneurysm.
AB  - Sympathetic cardiopulmonary nerves arise from the cervical sympathetic trunks and
      travel alongside the great arteries to innervate the ventricles. Because of the
      proximity of the nerve and artery, cardiac sympathetic denervation may occur in
      patients who have just undergone surgery for the repair of an ascending aortic
      aneurysm. METHODS: To evaluate the cardiac sympathetic activity in aortic
      aneurysm, we performed cardiac 123I-metaiodobenzylguanidine (MIBG) imaging on 12
      patients (mean age +/- SD, 47 +/- 17 y) before and after the surgical repair of
      an aneurysm. Seven patients scheduled for coronary artery bypass grafting also
      underwent 123I-MIBG imaging as controls for open-chest surgery. Planar images
      were obtained at 15 min (early) and 4 h (delayed) after injection of 111 MBq 123I
      MIBG, and the cardiac 123I-MIBG uptake was graded quantitatively and visually.
      The quantitative evaluation was based on the heart-to-mediastinum ratio (H/M),
      and visual evaluation was performed by assigning a score of 0-3 (0 = absent, 1 =
      severely reduced, 2 = reduced, and 3 = normal). Heart rate variability using 24-h
      Holter electrocardiography was analyzed before and after the operation to
      generate a time-domain index of heart rate variability as an index of autonomic
      balance. RESULTS: In patients with aortic aneurysms, both early and delayed H/Ms
      were significantly decreased after the operation (early H/M: 1.84 +/- 0.16 before
      vs. 1.40 +/- 0.16 after, P = 0.001; delayed H/M: 1.79 +/- 0.38 before vs. 1.27 +/
      0.18 after, P = 0.004). Visual analysis of 123I-MIBG accumulation in early
      images showed absence of 123I-MIBG accumulation in 3 of 12 patients, a score of 1
      in 7 patients, and a score of 2 in 2 patients. In contrast, no significant
      difference between H/M before surgery and H/M after surgery was seen in patients
      who underwent coronary artery bypass grafting. The time-domain index of heart
      rate variability was significantly lower after the operation than before (135 +/-
      40 after vs. 96 +/- 27 before, P < 0.05). CONCLUSION: Cardiac sympathetic nerves
      are totally or partially denervated after the surgical repair of ascending aortic
      aneurysm.

PMID- 11535724
TI  - Time course evaluation of myocardial perfusion after reperfusion therapy by 99mTc
      tetrofosmin SPECT in patients with acute myocardial infarction.
AB  - Myocardial perfusion imaging with 99mTc-labeled agents immediately after
      reperfusion therapy can underestimate myocardial salvage. It is also conceivable
      that delayed imaging is useful for assessing the risk area. However, to our
      knowledge, very few studies have sequentially evaluated these image changes. We
      conducted 99mTc-tetrofosmin (TF) and 123I-beta-methyl-p-iodophenylpentadecanoic
      acid (BMIPP) SPECT before and after reperfusion to treat acute myocardial
      infarction and quantified changes in TF myocardial accumulation and reverse
      redistribution. METHODS: Seventeen patients with a first myocardial infarction
      underwent successful reperfusion. We examined SPECT images obtained at the onset
      (preimage), those acquired 30 min (early image) and 6 h (delayed image) after TF
      injection, and images acquired 1, 4, 7, and 20 d after reperfusion (post-1-d,
      post-4-d, post-7-d, and post-20-d image, respectively). We also examined BMIPP
      SPECT images after 7 +/- 1.8 d (BMIPP image). Polar maps were divided into 48
      segments to calculate percentage uptake, and time course changes in segment
      numbers below 60% were observed as abnormal area. Moreover, cardiac function was
      analyzed by gated TF SPECT on 1 and 20 d after reperfusion. RESULTS: In reference
      to the abnormal area on the early images, the post-1-d image was significantly
      improved compared with the preimage (P < 0.01) as was the post-7-d image compared
      with the post-1-d and post-4-d images (P < 0.05, respectively). However, post-20
      d and post-7-d images did not significantly differ. Therefore, the improvement in
      myocardial accumulation reached a plateau 7 d after reperfusion. On the other
      hand, the abnormal area on the delayed images was significantly greater (P <
      0.01) compared with that on the early images from 4 to 20 d after reperfusion, as
      the value was essentially constant. The correlations of the abnormal area between
      the preimage and the post-7-d delayed image, the preimage and the BMIPP image,
      and the post-7-d delayed image and the BMIPP image were very close (r = 0.963, r
      = 0.981, and r = 0.975, respectively). Gated TF SPECT revealed that the left
      ventricular ejection fraction was not significantly different (P = not
      significant) between 1 and 20 d after reperfusion, but regional wall motion was
      significantly different after reperfusion (P < 0.05). CONCLUSION: These results
      suggest that the interval between reperfusion therapy and TF SPECT should be 7 d
      to evaluate the salvage effect and that TF delayed and BMIPP images are both
      useful in estimation of risk area.

PMID- 11535725
TI  - Alendronate does not interfere with 99mTc-methylene diphosphonate bone scanning.
AB  - Several studies have found that administration of etidronate results in
      competitive interference with 99mTc-labeled bone scanning reagents. In contrast,
      in other studies this problem was not encountered with other bisphosphonates.
      METHODS: We prospectively studied 9 patients with hormone-refractory prostate
      cancer. 99mTc-methylene diphosphonate (MDP) bone scanning was performed before
      they received alendronate, and scanning was repeated a mean of 16.6 d afterward,
      when the patients had been receiving 40 mg alendronate daily for a mean of 6 d.
      In addition, 7 patients who underwent delayed scanning when they had been
      receiving alendronate for a mean of 111 d were also restudied. Quantitative whole
      body bone scanning was performed, and radioactivity deposited in the bone
      metastasis was determined using region-of-interest analysis. RESULTS: A <6%
      increase in whole-body retention of 99mTc-MDP was seen on the initial
      postalendronate scan compared with the baseline scan. No significant differences
      in activity were seen in the bone lesion evaluated on the baseline and initial
      postalendronate studies. The delayed postalendronate scan generally showed
      similar or higher tracer accumulation compared with the baseline scan.
      CONCLUSION: Alendronate did not competitively inhibit uptake of 99mTc-MDP in the
      skeleton or tumor metastasis. Use of alendronate before bone scanning is unlikely
      to result in decreased detection of lesions or falsely decreased 99mTc-MDP
      activity at metastatic bone tumor sites.

PMID- 11535726
TI  - Evaluation of limited blood sampling in a preceding 99mTc-labeled diagnostic
      study to predict the pharmacokinetics and myelotoxicity of 186Re-cMAb U36
      radioimmunotherapy.
AB  - 186Re-labeled chimeric monoclonal antibody U36 (cMAb U36) was recently evaluated
      in a phase I dose escalation study in head and neck cancer patients. All 13
      patients received 99mTc-labeled cMAb U36 before 186Re-cMAb U36
      radioimmunotherapy. The aim of this study was to evaluate the suitability of
      multiple or limited blood sampling to predict clearance, red marrow absorbed
      dose, and myelotoxicity of 186Re-cMAb U36. METHODS: Population pharmacokinetics
      of 186Re-cMAb U36 were analyzed with a nonparametric expectation algorithm (NPEM
      2) and used for Bayesian analysis of individual patient data to predict cMAb U36
      clearance. RESULTS: 186Re-cMAb U36 clearance was most accurately predicted (r =
      0.91, P < 0.001) with limited sampling for sample points 4 and 72 h after
      administration of 186Re-cMAb U36. These predictions were less accurate with 99mTc
      cMAb U36 (r = 0.51, P = 0.078 for multiple sampling; r = 0.47, P = 0.104 for
      sampling at 4 and 21 h after administration). Thrombocytopenia was found to be
      correlated with the red marrow absorbed dose and was equally well predicted by
      limited blood sampling after administration of 99mTc-cMAb U36 (r = 0.81, P <
      0.01) or 186Re-cMAb U36 (r = 0.79, P < 0.01). CONCLUSION: Limited sampling seems
      useful to predict pharmacokinetics and myelotoxicity of 186Re-cMAb U36.

PMID- 11535727
TI  - Molecular imaging and gene therapy.
AB  - Molecular imaging is an emerging field of study that deals with imaging of
      disease on a cellular or genetic level rather than on a gross level. Recent
      advances in this field show promise, particularly in the imaging of gene
      expression. This article reviews the use of nuclear medicine, magnetic resonance,
      and optic imaging to visualize gene expression. A review is presented of current
      in vitro assays for protein and gene expression and the translation of these
      methods into the radiologic sciences. The merging fields of molecular biology,
      molecular medicine, and imaging modalities may provide the means to screen active
      drugs in vivo, image molecular processes, and diagnose disease at a
      presymptomatic stage.

PMID- 11535728
TI  - Advantages of short-lived positron-emitting radioisotopes for intracoronary
      radiation therapy with liquid-filled balloons to prevent restenosis.
AB  - Balloon catheters filled with liquid radioisotopes provide excellent dose
      homogeneity for intracoronary radiation therapy but are associated with risk for
      rupture or leakage. We hypothesized that the safety of liquid-filled balloons may
      be improved once positron emitters with half-lives below 2 h are used instead of
      the high-energy beta-emitters 166Ho, 186Re, or 188Re, all of which have a longer
      half-life of at least 17 h. METHODS: To support this concept, the suitability of
      18F (half-life, 109.8 min), 68Ga (half-life, 67.6 min), 11C (half-life, 20.4
      min), 13N (half-life, 9.97 min), and 15O (half-life, 2.04 min) for intracoronary
      radiation therapy was evaluated. Potential tissue penetration of positron
      radiation was assessed in a series of phantom experiments using Gafchromic film.
      Antiproliferative efficacy of positrons emitted by 68Ga was investigated in vitro
      using cultured bovine aortic smooth muscle cells (BASMCs), and was compared with
      gamma-radiation emitted by 137Cs. To characterize the remaining risk, we
      estimated radiotoxicity after accidental intravascular balloon rupture on the
      basis of tabulated isotope-specific doses (ICRP 53) and compared these values
      with 188Re. RESULTS: Half-dose depth of tissue penetration measured in phantom
      experiments was 0.29 mm for 18F, 0.42 mm for 11C, 0.54 mm for 13N, 0.79 mm for
      15O, and 0.9 mm for 68Ga. Irradiation of cultured BASMCs with positron radiation
      (68Ga) induced dose-dependent inhibition of proliferation with complete
      proliferative arrest at doses exceeding 6 Gy. ED(50) and ED(80) were 2.5 +/- 0.4
      Gy (mean +/- SD) and 4.4 +/- 0.8 Gy, respectively. Antiproliferative efficacy was
      equal to that of the 662-keV gamma-radiation emitted by 137Cs (ED(50), 3.8 +/-
      0.2 Gy; ED(80), 8.0 +/- 0.3 Gy). Estimates made for patient whole-body and organ
      doses were generally below 50 mSv/1.85 GBq for all investigated positron
      emitters. The same dose estimates for 188Re were 6-20 fold higher. CONCLUSION:
      Among the studied radioisotopes, 68Ga is the most attractive source for liquid
      filled balloons because of its convenient half-life, sufficient positron energy
      (2.92 MeV), documented antiproliferative efficacy, and uncomplicated availability
      from a radioisotope generator. The safety profile for 68Ga is significantly
      better than that of 188Re, which suggests this radioisotope should be evaluated
      further in preclinical studies.

PMID- 11535729
TI  - Intravascular radiation therapy with radioactive liquid-filled balloons for
      inhibition of restenosis after angioplasty: a new opportunity for nuclear
      medicine?

PMID- 11535730
TI  - Assessment of residual coronary stenoses using 99mTc-N-NOET vasodilator stress
      imaging to evaluate coronary flow reserve early after coronary reperfusion in a
      canine model of subendocardial infarction.
AB  - Reperfusion is often incomplete after recanalization therapy because of the
      presence of residual coronary stenoses. Detecting mild to moderate stenoses
      requires assessing coronary flow reserve with vasodilator stress. 99mTc-(N-ethoxy
      N-ethyl-dithiocarbamato)nitrido (N-NOET) is a viability-independent flow tracer
      and thus may be well suited for assessing coronary flow reserve in the acute
      phase of reperfusion. METHODS: Twelve open-chest dogs underwent 60 min of total
      left anterior descending artery (LAD) occlusion followed by either full
      reperfusion (group 1; n = 4) or reperfusion through a residual critical stenosis
      (group 2; n = 8). 99mTc-N-NOET was given during peak vasodilator stress 165 min
      after reperfusion, and initial and 60-min delayed images were acquired. Regional
      blood flow was assessed with radiolabeled microspheres. RESULTS: Infarct size was
      similar in both groups (9% +/- 2% vs. 8% +/- 2% of left ventricle). Both initial
      (0.61 +/- 0.02 vs. 0.73 +/- 0.01; P < 0.01) and 60-min (0.67 +/- 0.02 vs. 0.80 +/
      0.01; P < 0.01) defect count ratios (LAD/left circumflex coronary artery [LCx])
      differentiated between the 2 groups, reflecting the greater diminution in
      coronary flow reserve in group 2 dogs (LAD/LCx flow ratios = 0.37 +/- 0.04 vs.
      0.57 +/- 0.09; P < 0.01). Interestingly, coronary flow reserve in the reperfused
      zone of group 1 was diminished despite the absence of a stenosis. Thus, the
      difference in 99mTc-N-NOET uptake between the 2 groups was less than expected.
      CONCLUSION: In this canine myocardial infarction model with some coronary flow
      reserve preservation, 99mTc-N-NOET imaging can detect residual coronary stenoses.
      However, with more prolonged occlusion resulting in more severe endothelial or
      microvascular dysfunction, it may be difficult to distinguish varying degrees of
      vessel patency using any coronary flow reserve technique.

PMID- 11535731
TI  - 99mTc-N-NOET imaging for myocardial perfusion: can it offer more than we already
      have?

PMID- 11535732
TI  - Pharmacokinetics of [18F]FETNIM: a potential marker for PET.
AB  - 18F-labeled fluoroerythronitroimidazole (FETNIM) has been suggested as a marker
      of tumor hypoxia for use with PET. Our goal was to evaluate the pharmacokinetic
      properties of [18F]FETNIM in rats and analyze metabolites in human, dog, and rat
      plasma and urine. Metabolites in liver and tumor homogenates from tumor-bearing
      rats, as well as the biodistribution of the tracer, were also studied. METHODS:
      Radio-thin-layer chromatography and digital autoradiography were used to
      distinguish metabolites from the parent drug in urine and plasma from 8 patients,
      3 dogs, and 18 rats, as well as in liver and tumor homogenates from Sprague
      Dawley rats bearing 7,12-dimethylbenzanthracene-induced rat mammary carcinoma.
      Biodistribution of [18F]FETNIM was also studied in rats at 15, 30, 60, 120, and
      240 min after tracer injection. RESULTS: Most of the radioactivity in plasma and
      urine was the unchanged tracer, whereas rat liver homogenates contained almost
      only metabolites of [18F]FETNIM. None of the species studied showed binding of
      tracer to plasma proteins. A large variation-3%-70%-in the radioactivity
      represented by unchanged [18F]FETNIM was found in rat tumor. A negative
      correlation was found between the percentage of radioactivity represented by
      unchanged [18F]FETNIM in tumor tissue and tumor uptake (percentage injected dose
      per gram of tissue) at later times. The highest radioactivity was seen in urine
      and kidney; the lowest uptake was in fat, cerebellum, and bone matrix. In
      contrast to matrix, bone marrow had high uptake of 18F. The tumor-to-blood ratio
      reached a maximum of 1.80 +/- 0.64 at 2 h. CONCLUSION: We conclude that
      [18F]FETNIM shows low peripheral metabolism, little defluorination, and possible
      metabolic trapping in hypoxic tumor tissue. These suggest a potential use for
      this tracer in PET studies on hypoxia of cancer patients.

PMID- 11535733
TI  - A 3-step pretargeting strategy to image infection.
AB  - A new 3-step approach to imaging infectious and inflammatory foci was developed
      and optimized in a rat model. The approach relies on the nonspecific localization
      of an anti-diethylenetriaminepentaacetic acid (DTPA) antibody in inflamed tissue.
      In this study, the 3-step strategy was optimized by selecting the most suitable
      radiolabeled hapten and tuning the dosing schedule. METHODS: Wistar rats with
      Staphylococcus aureus infection in the left calf muscle were primed with the anti
      DTPA antibody DTIn-1 (0.67, 2, or 6 nmol per rat). In the second step (1-24 h
      later), the anti-DTPA activity in the circulation was blocked with unlabeled
      bovine serum albumin DTPA-In (0.3, 1, or 3 nmol per rat). In the third step (5-30
      min later), the radiolabeled hapten (monovalent or bivalent 111In-DTPA) was
      administered. The in vivo distribution of the radiolabel was monitored by
      scintigraphic imaging and by ex vivo counting of dissected tissues. RESULTS:
      Scatchard analysis revealed that the affinity of DTIn-1 for bivalent DTPA-111In
      (111In-diDTPA) was 6 times higher than the affinity for monovalent 111In-DTPA
      (K(a) = 0.87 x 10(-9) mol/L vs. 5.3 x 10(-9) mol/L). The uptake of the bivalent
      chelate in the abscess was 2.5-fold higher than that of monovalent 111In-DTPA.
      Most important, the bivalent chelate was completely retained in the abscess over
      time. Using the bivalent chelate, the optimal dosing scheme was determined with
      respect to the DTIn-1 dose (2 nmol per rat), the blocking agent dose (1 nmol per
      rat), and radiolabeled chelate dose (40 pmol per rat). The procedure was rapid;
      the infectious focus was clearly visualized 1 h after injection of the 111In
      labeled diDTPA, which was 5 h after administration of the anti-DTPA antibody. The
      nontargeted radiolabel rapidly cleared to the urine, only being retained in the
      abscess and the kidneys (4-6 percentage injected dose). Finally, an N2S2 core was
      attached to the diDTPA compound, allowing the use of 99mTc. CONCLUSION: This 3
      step approach enables rapid imaging of infectious foci with minimal uptake in
      noninflamed tissues.

PMID- 11535735
TI  - Dosimetry estimations for 123I-IAZA in healthy volunteers.
AB  - 123I-Labeled iodoazomycin arabinoside (IAZA) is a marker of hypoxia in vivo. It
      has been used clinically to image hypoxic tissue in solid tumors, peripheral
      vascular disease of diabetic origin, blunt brain trauma, and rheumatoid joints
      and in an animal model of cerebrovascular disease. The radiation dose
      biodistribution for 123I-IAZA was studied to assess and characterize its
      suitability as a clinical radiopharmaceutical. METHODS: Six healthy volunteers
      each received a nominal 185-MBq (5 mCi) dose of 123I-IAZA administered as a slow
      (1-3 min) intravenous injection in the arm. Anterior and posterior whole-body
      planar images were acquired for each volunteer beginning immediately after
      injection and at 1-2, 3-4, 6-8, and 20-24 h after injection. Venous blood samples
      (0 h predose through 28 h after dosing) and 28-h cumulative urine samples were
      taken from each volunteer for pharmacokinetic analysis. Radiation dose estimates
      were performed for all volunteers, with "reference adult" (for men) and "adult
      female" (for women) phantoms, and both the International Commission on
      Radiological Protection 30 gastrointestinal tract model and the dynamic bladder
      model, using the MIRDOSE3 program. Two sets of estimates, 1 using a
      pharmacokinetic analysis of total serum radioactivity and 1 based on
      scintigraphic image data, were obtained for each volunteer after 123I-IAZA
      administration. RESULTS: Two compartments were discernible by pharmacokinetic
      analysis, and 4 compartments were discernible by image analysis. The urinary
      bladder wall received the greatest radiation dose (6.3E-02 +/- 8.7E-03 mGy/MBq),
      followed by the upper large intestinal wall (5.6E-02 +/- 1.2E-02 mGy/MBq), the
      lower large intestinal wall (5.0E-02 +/- 1.2E-02 mGy/MBq), and the thyroid (4.4E
      02 +/- 1.4E-02 mGy/MBq). Approximately 90% of physiologically eliminated
      radioactivity was excreted through the kidneys. Radioactivity entering the
      intestinal tract from the gallbladder constituted <10% of biologically eliminated
      activity. CONCLUSION: The dosimetric analysis of 123I-IAZA in 6 healthy
      volunteers indicated that both disposition kinetics and radiation dosimetry
      support its clinical use for imaging tissue hypoxia.

PMID- 11535734
TI  - Dual time point 18F-FDG PET imaging for differentiating malignant from
      inflammatory processes.
AB  - The aim of this study was to investigate the difference in the rates of FDG
      uptake between malignant and inflammatory cells and processes. METHODS:  IN VITRO
      STUDIES: (18)F-FDG uptake by different tumor cell lines (human mesothelioma
      [REN]; rat mesothelioma [II45]; mice melanoma [B18F10]; mice mesothelioma [AB12];
      human myeloma [GM1500]; and human ovarian cancer [SKOV3]) and peripheral blood
      mononuclear cells isolated from 8 healthy human volunteers was measured 20 and 60
      min after FDG was added into growth medium. Animal studies: II45 cells were
      implanted into the left flank of rats (n = 5) and a focal inflammatory reaction
      (mechanical irritation) was generated in the right flank. PET images at 45 and 90
      min after injection of FDG were obtained and standardized uptake values (SUVs)
      were determined. Patient studies: Seventy-six patients who had dual time FDG PET
      scans were retrospectively analyzed. All results were expressed as the percentage
      change in SUV of the later time image from that of the earlier time (mean +/-
      SD). RESULTS:  IN VITRO STUDIES: Except for the SKOV3 cell line, which had only
      minimally increased FDG uptake (+10% +/- 26%; P > 0.3), all other tumor cell
      lines tested showed significantly increased FDG uptake over time (GM1500, +59% +/
      19%; B18F10, +81% +/- 15%; AB12, 93% +/- 21%; II45, +161% +/- 21%; REN, +198% +/
      48%; P < 0.01 for all). By contrast, FDG uptake in mononuclear cells was
      decreased in 7 of 8 donors. Animal studies: SUVs of tumors from 90-min images
      were significantly higher than those from 45-min images (+18% +/- 8%; P < 0.01),
      whereas the SUVs of inflammatory lesions decreased over time (-17% +/- 13% of the
      early images; P < 0.05). CLINICAL STUDIES: The SUVs of delayed images from the
      known malignant lesions compared with those of earlier scans increased over time
      (+19.18% +/- 9.58%; n = 31; P < 0.001; 95% confidence interval, 15.8%-22.6%). By
      contrast, the SUVs of benign lung nodules decreased slightly over time (-6.3% +/-
      8.1%; n = 12; P < 0.05; 95% confidence interval, -10.9% to -1.7%). The SUV of
      inflammatory lesions caused by radiation therapy (+1.16% +/- 7.23%; n = 8; P >
      0.05; 95% confidence interval, -3.9%-6.2%) and the lesions of painful lower limb
      prostheses (+4.03% +/- 11.32%; n = 25; P > 0.05; 95% confidence interval, -0.4%
      8.5%) remained stable over time. CONCLUSION: These preliminary data show that
      dual time imaging appears to be useful in distinguishing malignant from benign
      lesions. Further research is necessary to confirm these results.

PMID- 11535736
TI  - Evidence-based risk assessment in noninvasive imaging.
AB  - Assessment of important clinical and economic outcomes has become central to the
      evaluation of patient care. Outcome research is deeply rooted in epidemiology,
      including the use of multivariable, risk-adjusted regression analysis. In our
      current health care environment, these methods are increasingly being used to
      assess the quality of care and to profile physicians and laboratories. Nuclear
      medicine physicians therefore need to better understand outcome methodologies in
      order to evaluate patient outcomes, develop guidelines, and decide on patient
      management. METHODS: This review describes the methods of assessing the
      diagnostic and prognostic value of nuclear medicine techniques and, briefly, the
      methodologic limitations of sample size, frequency and type of events, and follow
      up periods and the incremental value of imaging. Also described are logistic
      regression and Cox proportional hazards modeling. Models for risk assessment are
      designed to identify whether patients require conservative (i.e., low-risk) or
      aggressive (i.e., high-risk) treatment. Treatment selection is currently based on
      risk assessment and the formation of an integrated, empiric risk stratification
      algorithm of care. This review also includes the methods of assessing economic
      effectiveness and quality-of-life issues for patients examined with nuclear
      medicine techniques. CONCLUSION: In this era of constrained resources, low-cost
      outpatient-based care may be of increasing importance. High-quality evidence of
      the clinical and economic outcome of nuclear imaging is essential for helping
      health care providers and payers assess its value.

PMID- 11535737
TI  - Methodologic aspects of myocardial blood flow quantification with 1-11C-acetate
      PET.

PMID- 11535738
TI  - Parenchymal mean transit time analysis.

PMID- 11535739
TI  - From rectangles to triangles.

PMID- 11535741
TI  - HIV / AIDS in the age of palliative care. Foreword.

PMID- 11535742
TI  - The evolution of palliative care.

PMID- 11535743
TI  - Remembering death: public policy in the USA.

PMID- 11535744
TI  - UK strategies for palliative care.

PMID- 11535745
TI  - The changing epidemiology of HIV infection: new challenges for HIV palliative
      care.

PMID- 11535746
TI  - Clinical dilemmas in palliative care for HIV infection.

PMID- 11535747
TI  - Access to palliative care in the USA: why emphasize vulnerable populations?

PMID- 11535748
TI  - Inequalities in the UK.

PMID- 11535750
TI  - Financing end-of-life care in the USA.

PMID- 11535751
TI  - Healthcare financing for the under-served: UK.

PMID- 11535753
TI  - From cradle to grave: palliative medicine education in the UK.

PMID- 11535754
TI  - Professional education in end-of-life care: a US perspective.

PMID- 11535756
TI  - End-of-life issues in AIDS: the research perspective.

PMID- 11535757
TI  - Palliative care research for the National Health Service.

PMID- 11535759
TI  - Palliative care for the poor and disenfranchised: a view from the Robert Wood
      Johnson Foundation.

PMID- 11535760
TI  - Risk-taking and innovation: a view from the Nuffield Trust.

PMID- 11535761
TI  - The Project on Death in America.

PMID- 11535762
TI  - Palliative care in the age of HIV / AIDS. Conclusions from the meeting.

PMID- 11535763
TI  - Reporting standards for uterine artery embolization for the treatment of uterine
      leiomyomata.

PMID- 11535764
TI  - Image-guided radiofrequency tumor ablation: challenges and opportunities--part I.

PMID- 11535765
TI  - Risk stratification and outcomes of transluminal endografting for abdominal
      aortic aneurysm: 7-year experience and long-term follow-up.
AB  - PURPOSE: To determine early and late outcomes of transluminal endografting (TE)
      in patients with abdominal aortic aneurysm (AAA), stratified by predicted risk of
      procedure-related mortality with conventional operation. MATERIALS AND METHODS: A
      retrospective study was conducted in consecutive risk-stratified AAA patients
      undergoing TE at a not-for-profit cardiovascular referral center from March 1994
      through November 2000 with follow-up through February 2001. With use of
      conventional risk strata (0 = low, 1 = minimal, 2 = moderate, and 3 = high),
      predicted procedure-related mortalities were 0%-1% in stratum 0 (n = 40), 1%-3%
      in stratum 1 (n = 118), 3%-8% in stratum 2 (n = 116), and 8%-30% in stratum 3 (n
      = 31). Main outcome measures were: (i) TE procedural success, (ii) procedure
      related mortality, (iii) major nonfatal complications, (iv) composite adverse
      outcome (ii + iii), (v) length of stay (LOS), (vi) freedom from AAA rupture,
      (vii) late survival, (viii) late complications, and (ix) endoleaks and their
      classification and management. RESULTS: Women were significantly less likely than
      men to qualify for and undergo endografting: 24 of 91 (26.4%) women underwent TE,
      compared to 281 of 684 (41.1%) men. Of 305 attempted TE procedures, 291 (95.4%)
      were successful, four (1.3%) were urgently converted to open repair, and 10
      (3.3%) were aborted. Procedure-related mortalities occurred in eight cases (2.6%)
      overall and one of 40 (2.5%), one of 118 (0.8%), four of 116 (3.4%), and two of
      31 (6.5%) cases for risk strata 0-3, respectively. Perioperative survivors were
      significantly younger than nonsurvivors (74.3 y +/- 9 vs 81.6 y +/- 5.1; P
      =.0087). Forty-six patients (15.1%) had major complications. Composite adverse
      outcome was worse for patients in stratum 3 than those in stratum 1 (P =.0296)
      and those in strata 0, 1, and 2 combined (P =.026). Procedure-related mortality
      declined with institutional experience, from 4% among the first 100 patients
      undergoing TE to 1% among the last 105. For strata 0-3, median LOS were 2, 3, 3,
      and 4 days, respectively. Seventy patients (22.9%) had 75 endoleaks, of which 30
      necessitated additional procedures, 17 self-resolved, and 22 were untreated as of
      March 1, 2001. Five patients with endoleak died of unrelated causes. One late
      onset type IA endoleak (26 mo) resulted in the only AAA rupture and death in the
      follow-up period among the 291 patients who underwent successful transluminal
      endograft implantation. Actuarial survival rates at 1 year after TE were 90.3% +/
      1.9% for the overall study group and 97.5% +/- 2.5%, 94% +/- 2.5%, 86.9% +/-
      3.3%, and 81.3% +/- 7.7% for risk strata 0-3, respectively. At 5 years, overall
      actuarial survival was 69.6% +/- 6.1%. Thirty-eight late deaths were attributable
      to post-TE AAA rupture (n = 1), AAA rupture late after failed TE with no further
      treatment (n = 1), other cardiovascular disorders (n = 7), cancer (n = 15), other
      causes (n = 10), and unknown causes (n = 4). Late deaths occurred in risk strata
      0-3 at the following rates: two of 40 (5%), 10 of 118 (8.5%), 16 of 116 (13.8%),
      and 10 of 31 (32.3%), respectively (stratum 0 vs stratum 3, P =.0017; stratum 1
      vs stratum 3, P =.003). CONCLUSIONS: TE is safe and confers durable protection
      against AAA rupture in treated populations. Still, protection is not absolute in
      patients with endoleaks, because late AAA enlargement and even rupture can occur.
      Given current knowledge, technology, and practice, careful patient selection and
      close surveillance of patients after implantation of transluminal endografts is
      essential.

PMID- 11535766
TI  - The influence of female gender on the outcome of endovascular abdominal aortic
      aneurysm repair.
AB  - PURPOSE: Women appear to have a greater risk of death than men after open surgery
      for abdominal aortic aneurysm (AAA). The aim of this study is to compare outcomes
      after endovascular AAA repair in men and women. MATERIALS AND METHODS: From March
      1994 to November 2000, 305 patients (281 men and 24 women) underwent AAA repair
      with use of endovascular techniques. Outcomes measured included perioperative
      mortality, percentage of procedures aborted or converted to open abdominal AAA
      repair, deployment success rate, angiographic success rate, major complication
      rate, and percentage of patients with endoleaks. RESULTS: Patients of both
      genders were comparable with respect to mean age (74.4 in men vs 75.9 in women;
      NS). According to the Society for Vascular Surgery/International Society of
      Cardiovascular Surgery risk stratification method, men and women were also
      comparable in age risk score (0.60 vs 0.67; NS), pulmonary risk score (0.50 vs
      0.83; NS), and renal risk score (0.28 vs 0.17; NS). However, the cardiac risk
      score was higher in men (1.31 vs 0.80; P <.05) and maximum AAA diameter was
      greater in men (57.0 mm vs 52.1 mm; P <.01). Eight perioperative deaths (2.6%)
      occurred (2.8% of men, 0% of women; NS). Proportionately more procedures were
      aborted in women than men: four (16.7%) versus six (2.1%; P <.01). Conversion to
      open repair occurred in four men (1.4%) and no women (NS). Deployment success was
      achieved in 96.4% of men and 83.3% of women (P <.01). Angiographic success was
      achieved in 84.1% of men and 80% of women (NS). Of 46 major complications, 42
      (14.9%) occurred in 281 men and four (16.7%) occurred in 24 women (NS). Sixty
      seven patients had endoleaks: 60 were men (22.1%) and seven were women (35%; NS).
      CONCLUSIONS: There was no difference between men and women with respect to
      perioperative mortality and major complication rates. These findings indicate
      that being a woman does not adversely influence the outcome of endovascular AAA
      repair. However, women had a higher rate of aborted procedures. Precise
      preoperative evaluation may help reduce this problem in women.

PMID- 11535767
TI  - Gunther Tulip Retrievable Vena Cava Filter: results from the Registry of the
      Canadian Interventional Radiology Association.
AB  - PURPOSE: To report data collected by the Canadian Registry of the Gunther Tulip
      Retrievable Filter (GTF). MATERIALS AND METHODS: Between February 1998 and
      December 2000, 90 patients at eight hospitals underwent implantation of 91 GTFs.
      There were 45 male patients and 45 female patients, age 17-88 years, with a mean
      age of 49 years. Indications for filter placement were pulmonary embolism (PE) or
      deep vein thrombosis (DVT) with a contraindication to anticoagulation in 83
      patients, prophylaxis after massive PE in one, prophylaxis for proximal free
      floating thrombus in one, and prophylaxis with no DVT or PE in six patients
      (major trauma, n = 4; high preoperative risk, n = 2). GTF retrieval was attempted
      in selected patients from a right internal jugular vein approach. RESULTS: One
      GTF was inadvertently placed in the right iliac vein and could not be retrieved.
      There were no other major placement complications. GTF retrieval was attempted in
      52 patients (53 GTFs); 52 GTFs were successfully retrieved from 51 patients.
      Implantation times were 2-25 days (mean, 9 d). Of these 51 patients, 37 underwent
      follow-up for 5-420 days (mean, 103 d) after filter retrieval. Four patients (8%
      of retrieved GTFs) required reinsertion of a permanent filter 17-167 days (mean,
      78 d) after GTF retrieval as a result of bleeding from anticoagulation (n = 2) or
      because the patient required further surgery (n = 2). One other patient had
      recurrent DVT 230 days after retrieval; no PE or other complication was
      documented in the retrieval group. GTFs were not retrieved from 39 patients for
      various reasons. Of these 39 patients, 25 underwent follow-up 7-420 days (mean,
      85 d) after filter placement. Two patients developed filter occlusion (5%); no
      other complications were documented. CONCLUSION: The GTF has a broad range of
      utility: it can be used as a permanent filter or retrieved after implantation
      periods of 15 days and possibly longer. However, indications for retrieval
      require further study, as does the maximum implantation time.

PMID- 11535768
TI  - Initial experience with use of tris-acryl gelatin microspheres for uterine artery
      embolization for leiomyomata.
AB  - PURPOSE: To assess the safety and effectiveness of tris-acryl gelatin
      microspheres (Embospheres) in the treatment of leiomyomata by uterine artery
      embolization. MATERIALS AND METHODS: This was a Phase I study of 30 patients with
      symptomatic leiomyomata. Each patient underwent ultrasound imaging and completed
      questionnaires regarding symptoms and health status at baseline and 3 and 6
      months after treatment. Bilateral embolization was performed with use of tris
      acryl gelatin microspheres. Summary statistics were used to characterize the
      demographic and procedure data. Paired t-tests were used to assess change in the
      severity of menstrual bleeding and health-related quality of life. RESULTS:
      Bilateral embolization was technically successful in all patients. Three months
      after treatment, menstrual bleeding was markedly improved as assessed by
      menorrhagia questionnaire (P <.0001) and menstrual calendar (P <.0001). Pelvic
      pain and discomfort was improved in 92% of cases. Physical component summary
      scores of the SF-12 also increased from baseline at 3 months (P =.02) and at 6
      months (P =.01). Minor complications occurred in nine patients; there were no
      major complications. CONCLUSION: Although limited, this initial experience
      suggests that tris-acryl gelatin microspheres are an effective and safe embolic
      agent for the treatment of uterine leiomyomata.

PMID- 11535769
TI  - Intraarterial lidocaine for pain control after uterine artery embolization for
      leiomyomata.
AB  - PURPOSE: To evaluate the effectiveness of intraarterial lidocaine in controlling
      pain after uterine artery embolization (UAE). MATERIALS AND METHODS: In this
      double-blind prospective study, patients undergoing UAE received preservative
      free 1% lidocaine or saline solution (control) in the uterine arteries before
      embolization. Postprocedural pain was managed with patient-controlled intravenous
      morphine. Attempted doses, number of doses received, total morphine dose, and
      maximum pain numeric rating scale (NRS) score during the postprocedural
      hospitalization were recorded and compared. Three-month follow-up magnetic
      resonance (MR) imaging and symptomatic questionnaires were collected and
      compared. RESULTS: Ten patients received lidocaine and eight patients received
      placebo. Moderate to severe vasospasm was noted in seven patients after lidocaine
      injection, whereas no vasospasm was noted in the placebo group (P =.004).
      Patients in the lidocaine group had lower NRS pain scores than those in the
      placebo group (P =.012), whereas there was no difference in morphine requirement
      between treated patients and control subjects. The study was terminated after 18
      patients were treated as a result of unexpected vasospasm. CONCLUSIONS:
      Intraarterial 1% lidocaine is associated with moderate to severe vasospasm.
      Lidocaine significantly lowers subjective pain, but there is no difference in
      analgesic requirements. The routine use of intraarterial lidocaine is not
      recommended for pain control until the long-term effects of vasospasm on outcome
      is known.

PMID- 11535770
TI  - The vascular impact of uterine artery embolization: prospective sonographic
      assessment of ovarian arterial circulation.
AB  - PURPOSE: The etiology of premature ovarian failure after uterine artery
      embolization (UAE) is unknown. The authors prospectively assessed ovarian
      arterial circulation before and after UAE with use of ultrasonography (US). The
      authors hypothesize that nontarget embolization of the ovary occurs during
      routine UAE. MATERIALS AND METHODS: Twenty-three women (mean age of 42.6 years;
      range, 35-51 y) participated in the study. Grayscale, color, and pulsed-wave
      Doppler US studies were performed immediately before and after UAE. Resistive
      index (RI) and pulsatility index (PI) were calculated. The proportion of women
      who developed increased vascular impedance after UAE was statistically assessed
      with use of the Yates-corrected chi(2) test. RESULTS: Seventeen of 23 patients
      (74%) completed the study. Nine of 17 (54%) showed complete loss of ovarian
      arterial perfusion after UAE. Six of 17 (35%) had increases in RI and PI, whereas
      two of 17 (11%) had decreases in RI and PI. The increase in vascular impedance
      after UAE in 15 of 17 patients was significant (P <.0001). CONCLUSION: Loss of
      detectable ovarian arterial perfusion occurs in the majority of patients
      undergoing UAE. Ovarian vascular impedance increases in nearly all patients as a
      result of UAE. The authors conclude that inadvertent nontarget embolization of
      the ovarian arterial bed occurs during routine UAE.

PMID- 11535771
TI  - Mechanical thrombolysis of venous thrombosis in an animal model with use of
      temporary caval filtration.
AB  - PURPOSE: To test the effect of temporary caval filtration on pulmonary emboli
      when a mechanical thrombolytic device is used to treat venous thrombosis and to
      test the effects of a modified device on caval patency at 30-day follow-up.
      MATERIALS AND METHODS: In a canine model of iliocaval subacute thrombosis,
      mechanical thrombolysis was performed with use of an 8-F over-the-wire Arrow
      Trerotola Percutaneous Thrombolytic Device (PTD) with a 9-mm (iliac) or 15-mm
      (inferior vena cava [IVC]) basket. In six procedures, the device was made of
      nitinol monofilament, and in another six, it was made of braided stainless steel.
      All procedures were performed with a nitinol expandable sheath (temporary filter)
      in the suprarenal IVC. Low-molecular-weight heparin was given daily after the
      procedure. Venography, pulmonary arteriography, measurement of blood gases, and
      pulmonary artery (PA) pressure measurement were performed before and after the
      procedure and at 30-day follow-up. Pulmonary arteriograms from the group treated
      with stainless-steel devices were compared to those from an earlier group of
      animals in which the identical procedure was performed without caval filtration.
      The IVC was examined histologically. RESULTS: Thrombolysis was successful in all
      animals. Rare segmental and subsegmental pulmonary emboli (PE) were seen
      arteriographically; compared to procedures without filters, there was a
      significant reduction in PE (P <.002). However, a mild increase in pulmonary
      artery pressure, decrease in pH, and increase in pCO(2) were observed
      postprocedurally. At 30-day follow-up (n = 11), IVC patency was preserved in 45%
      (n = 5) of animals overall. Caval patency was significantly better in animals in
      which the combination of stainless-steel devices was used (five of six = 83% vs
      zero with nitinol device; P =.015). Histologically, the stainless-steel device
      caused little intimal injury and fibrosis-less than that seen with the nitinol
      device. CONCLUSIONS: Temporary filtration reduces, but does not completely
      eliminate, PE during mechanical thrombolysis. The stainless-steel device results
      in less intimal injury and better caval patency than the nitinol device.

PMID- 11535772
TI  - Vacuum-assisted resection of malignant tumors with and without subsequent
      radiofrequency ablation: feasibility of complete tumor treatment tested in an
      animal model.
AB  - PURPOSE: To evaluate the feasibility of vacuum-assisted tumor excision with and
      without RF ablation for the minimally invasive treatment of small tumors.
      MATERIALS AND METHODS: Twenty VX2 tumors were implanted bilaterally into the
      spine muscle of 10 rabbits. Tumor excision was performed after tumor sizes
      reached 10 mm (12-27 d incubation) with use of a vacuum-assisted biopsy device.
      Three or four directed vacuum-assisted biopsies were performed in angle steps of
      30 degrees. In 10 tumors, ultrasound (US)-guided radiofrequency (RF) ablation (8
      min, 60 W) was subsequently performed with use of a cooled-tip electrode system.
      Follow-up US was performed at 3-4-day intervals for as long as 3 weeks after
      excision/RF ablation. Autopsy and histopathologic analysis were performed.
      RESULTS: The duration of vacuum excision ranged from 12 to 45 minutes (25 min +/-
      7). Histologically tumor-free margins in the outer round of the core biopsy
      specimens were found in only four of 20 cases (20%). Maximum lesion sizes during
      RF ablation ranged from 18 to 25 mm (20 mm +/- 2.6). Histologic examination of
      the excision specimens documented tumor-free margins in only three tumors (30%)
      among the excision-only group and only one (10%) among the combined
      excision/ablation group. Local recurrences occurred in eight of 10 cases (80%)
      after vacuum excision alone, whereas recurrence after combined excision and RF
      ablation occurred only in two of 10 cases (20%; P <.05). CONCLUSIONS: Local tumor
      resection with use of vacuum-assisted biopsy is feasible and promising as a
      minimally invasive therapy for the treatment of small focal breast neoplasms.
      Combined excision and RF ablation techniques may reduce the rate of local
      recurrence considerably.

PMID- 11535773
TI  - Arteriovenous malformation of the mandible: embolization and direct injection
      therapy.
AB  - Arteriovenous malformation (AVM) of the mandible is a rare entity but one that
      can be potentially fatal as a result of massive hemorrhage. Traditional treatment
      involved extensive surgical resection of the mandible. With the advent of
      improved endovascular techniques, interventional radiology is now the best method
      to control active hemorrhage and ultimately cure these lesions. The authors
      describe three cases of successfully treated mandibular AVM by percutaneous
      and/or endovascular techniques.

PMID- 11535774
TI  - Transjugular intrahepatic portosystemic shunt placement in the setting of
      polycystic liver disease: questioning the contraindication.
AB  - Although polycystic liver disease has long been listed as a contraindication to
      transjugular intrahepatic portosystemic shunt (TIPS) creation, two cases of TIPS
      placement in that particular clinical setting have been reported. Another case is
      reported in this article and the clinical course over 21 months of follow-up is
      examined. The discussion reviews the mechanics of TIPS creation in a polycystic
      liver and the vague premise of the polycystic liver as a contraindication to
      TIPS.

PMID- 11535775
TI  - The feasibility of retrograde catheterization of the right gastric artery via the
      left gastric artery.
AB  - Retrograde catheterization of the right gastric artery was attempted in 22
      patients for the purpose of proximal right gastric artery embolization.
      Retrograde catheterization was successfully performed in 12 of the 14 patients
      (86%) with smooth anastomoses. Retrograde catheterization was unsuccessful (n =
      1) or time-consuming (n = 1) in two patients (14%) with smooth anastomoses. Right
      gastric artery embolization was successfully performed with microcoils in 13 of
      the patients. In all eight patients with tortuous anastomoses, catheterization
      was unsuccessful. Retrograde catheterization should be considered possible when
      preliminary angiography indicates a smooth anastomosis with the left gastric
      artery.

PMID- 11535776
TI  - Stent placement in the treatment of pulmonary artery stenosis secondary to
      fibrosing mediastinitis.
AB  - This article describes an initial experience with stent placement in three
      patients with severe pulmonary artery stenosis secondary to fibrosing
      mediastinitis. All three patients were severely symptomatic on admission and all
      three were asymptomatic after treatment and remained symptom-free approximately 1
      year after treatment.

PMID- 11535777
TI  - Percutaneous repair of an iatrogenic laceration of the left bile duct with a
      covered stent.
AB  - The presence of biliary leaks after liver resections is not an unusual problem,
      especially after extended hepatectomies. The usual treatment of choice for
      biliary duct injuries is to decompress the biliary system with draining
      catheters. Persistent biliary fistulas are nevertheless a challenging problem
      when endoscopic or percutaneous approaches fail to achieve occlusion of the bile
      leakage. The authors report a bile duct injury after a right lobe hepatectomy
      treated percutaneously with placement of a covered stent. After 6 months, the
      patient was tube-free and without any episode of cholangitis or bile duct
      dilation. Longer follow-up will clarify the future role of this kind of device in
      biliary system lacerations.

PMID- 11535778
TI  - Retrieval of entrapped guide wire in an IVC filter facilitated with use of a
      myocardial biopsy forceps and snare device.

PMID- 11535779
TI  - Thiamin auxotrophy in yeast through altered cofactor dependence of the enzyme
      acetohydroxyacid synthase.
AB  - The THI1 gene of Saccharomyces cerevisiae has been identified and found to be
      allelic with the previously characterized gene ILV2 that encodes acetohydroxyacid
      synthase (AHAS). This enzyme catalyses the first step in the parallel
      biosyntheses of the branched-chain amino acids isoleucine and valine, using
      thiamin pyrophosphate (TPP) as a cofactor. The ilv2-thi1 allele encodes a
      functional AHAS enzyme with an altered dependence for the cofactor TPP resulting
      in the thiamin auxotrophic phenotype. Nucleotide sequence analysis and site
      directed mutagenesis revealed that the thi1 mutation is a single base
      substitution which causes the conserved amino acid substitution D176E in the AHAS
      protein. This study therefore implicates aspartate 176 as another amino acid
      residue important either for the efficient binding of TPP by AHAS or for the
      functional stability of the holoenzyme.

PMID- 11535780
TI  - Identification of the heat-shock sigma factor RpoH and a second RpoH-like protein
      in Sinorhizobium meliloti.
AB  - Hybridization to a PCR product derived from conserved sigma-factor sequences led
      to the identification of two Sinorhizobium meliloti DNA segments that display
      significant sequence similarity to the family of rpoH genes encoding the
      sigma(32) (RpoH) heat-shock transcription factors. The first gene, rpoH1,
      complements an Escherichia coli rpoH mutation. Cells containing an rpoH1 mutation
      are impaired in growth at 37 degrees C under free-living conditions and are
      defective in nitrogen fixation during symbiosis with alfalfa. A plasmid-borne
      rpoH1-gusA fusion increases in expression upon entry of the culture into the
      stationary phase of growth. The second gene, designated rpoH2, is 42% identical
      to the S. meliloti rpoH1 gene. Cells containing an rpoH2 mutation have no
      apparent phenotype under free-living conditions or during symbiosis with the host
      plant alfalfa. An rpoH2-gusA fusion increases in expression during the stationary
      phase of growth. The presence of two rpoH-like sequences in S. meliloti is
      reminiscent of the situation in Bradyrhizobium japonicum, which has three rpoH
      genes.

PMID- 11535781
TI  - Saccharomyces cerevisiae commits to a programmed cell death process in response
      to acetic acid.
AB  - Recent evidence has revealed the occurrence of an apoptotic phenotype in
      Saccharomyces cerevisiae that is inducible with oxidative stress. Here, exposure
      of S. cerevisiae to 20-200 mM acetic acid for 200 min at pH 3.0 resulted in cell
      death. Yeast mortality induced by 120-200 mM acid was not inhibited by
      cycloheximide and was accompanied by ultrastructural alterations typical of
      necrosis. In contrast, alterations associated with cell death induced by 20-80 mM
      acetic acid included: (i) cycloheximide-inhibitable chromatin condensation along
      the nuclear envelope; (ii) exposure of phosphatidylserine on the surface of the
      cytoplasmic membrane, revealed by the FITC-annexin V reaction; and (iii) the
      occurrence of DNA strand breaks, demonstrated by the TUNEL assay. These results
      show that a programmed cell death process sharing common features with an
      apoptotic phenotype can be induced by acetic acid in S. cerevisiae. This
      observation raises the possibility of this mode of cell death being more
      generalized in yeasts than previously considered and extended to cell death
      induced by other stress agents.

PMID- 11535782
TI  - Sigma A recognition sites in the Bacillus subtilis genome.
AB  - A hidden Markov model of sigma(A) RNA polymerase cofactor recognition sites in
      Bacillus subtilis, containing either the common or the extended -10 motifs, has
      been constructed based on experimentally verified sigma(A) recognition sites.
      This work suggests that more information exists at the initiation site of
      transcription in both types of promoters than previously thought. When tested on
      the entire B. subtilis genome, the model predicts that approximately half of the
      sigma(A) recognition sites are of the extended type. Some of the response
      regulator aspartate phosphatases were among the predictions of promoters
      containing extended sites. The expression of rapA and rapB was confirmed by site
      directed mutagenesis to depend on the extended -10 region.

PMID- 11535783
TI  - Production of the Gram-positive Sarcina ventriculi pyruvate decarboxylase in
      Escherichia coli.
AB  - Sarcina ventriculi grows in a remarkable range of mesophilic environments from pH
      2 to pH 10. During growth in acidic environments, where acetate is toxic,
      expression of pyruvate decarboxylase (PDC) serves to direct the flow of pyruvate
      into ethanol during fermentation. PDC is rare in bacteria and absent in animals,
      although it is widely distributed in the plant kingdom. The pdc gene from S.
      ventriculi is the first to be cloned and characterized from a Gram-positive
      bacterium. In Escherichia coli, the recombinant pdc gene from S. ventriculi was
      poorly expressed due to differences in codon usage that are typical of low-G+C
      organisms. Expression was improved by the addition of supplemental codon genes
      and this facilitated the 136-fold purification of the recombinant enzyme as a
      homo-tetramer of 58 kDa subunits. Unlike Zymomonas mobilis PDC, which exhibits
      Michaelis-Menten kinetics, S. ventriculi PDC is activated by pyruvate and
      exhibits sigmoidal kinetics similar to fungal and higher plant PDCs. Amino acid
      residues involved in the allosteric site for pyruvate in fungal PDCs were
      conserved in S. ventriculi PDC, consistent with a conservation of mechanism.
      Cluster analysis of deduced amino acid sequences confirmed that S. ventriculi PDC
      is quite distant from Z. mobilis PDC and plant PDCs. S. ventriculi PDC appears to
      have diverged very early from a common ancestor which included most fungal PDCs
      and eubacterial indole-3-pyruvate decarboxylases. These results suggest that the
      S. ventriculi pdc gene is quite ancient in origin, in contrast to the Z. mobilis
      pdc, which may have originated by horizontal transfer from higher plants.

PMID- 11535784
TI  - Regulation of the ldhA gene, encoding the fermentative lactate dehydrogenase of
      Escherichia coli.
AB  - The fermentative lactate dehydrogenase (LDH) of Escherichia coli is induced by
      low pH under anaerobic conditions. Both translational and transcriptional gene
      fusions to ldhA, which encodes the fermentative LDH, have now been made. Both
      types of ldhA-lacZ fusion were induced by low pH, but only in the absence of air.
      However, the translational fusions were consistently expressed at a five- to
      tenfold higher level than the transcriptional fusions, perhaps implying some post
      transcriptional effect on ldhA expression. Introduction of arcB::Kan decreased
      expression of both translational and transcriptional ldhA-lacZ fusions by three-
      to fivefold. Disruption of mlc, which encodes a repressor of several genes of the
      phosphotransferase system, almost abolished expression of ldhA. Disruption of
      csrA caused a moderate drop in expression of both operon and protein ldhA
      fusions, whereas insertional inactivation of csrB or glgA had the opposite
      effect. These effects are probably indirect, resulting from alterations in sugar
      accumulation versus storage. Mutations in ptsG, cra, fnr, narL, rpoS, osmZ, appY,
      ack/pta, aceEF, pfl and ldhA had no effect on expression of the ldhA fusions.
      ldhA was not induced by the membrane-permeant weak acid benzoate, implying that
      it does not respond to the internal pH directly. Little pH induction was seen
      during growth on glycerol plus fumarate, suggesting that products of sugar
      fermentation are necessary for acid induction. Addition of succinate, acetate or
      lactate had no effect on ldhA expression. In contrast, pyruvate caused a two- to
      fourfold increase in expression of ldhA-lacZ. This accords with the idea that
      increased sugar metabolism indirectly induces ldhA.

PMID- 11535785
TI  - Nitrogen source governs the patterns of growth and pristinamycin production in
      'Streptomyces pristinaespiralis'.
AB  - Phosphate-limited synthetic culture media were designed to investigate the growth
      and the pristinamycin production of 'Streptomyces pristinaespiralis' using
      different nitrogen sources. During balanced growth, either mineral or organic
      nitrogen sources were readily utilized. However, glutamate and alanine were used
      as both nitrogen and carbon source, sparing the utilization of the primary carbon
      source, glucose. Valine was utilized only for its nitrogen and consequently 2
      ketoisovalerate was excreted in the medium. Ammonium prevented the utilization of
      nitrate. Upon phosphate limitation, glycerol, originating from the breakdown of
      teichoic acids, was released, allowing the recovery of phosphate from the cell
      wall and the continuation of growth. Under such conditions, ammonium was excreted
      following the consumption of glutamate and alanine and was later reassimilated
      after exhaustion of the primary nitrogen source. The mode of utilization of
      valine prevented the production of pristinamycins due to excretion of 2
      ketoisovalerate, one of their direct precursors. For other nitrogen sources,
      pristinamycin production was controlled by nitrogen catabolic regulation linked
      to the residual level of ammonium. In the case of nitrate, the negative
      regulation was alleviated by the absence of ammonium and production then occurred
      precociously. In the case of amino acids and ammonium, production was delayed
      until after exhaustion of amino acids and depletion of ammonium.

PMID- 11535786
TI  - Energy metabolism of Actinobacillus actinomycetemcomitans during anaerobic and
      microaerobic growth in low- and high-potassium continuous culture.
AB  - Actinobacillus actinomycetemcomitans, a member of the gamma subclass of the
      Proteobacteria, has been implicated as the agent responsible for human
      periodontitis. In this study, A. actinomycetemcomitans 301-b was grown in
      fructose-limited chemostat cultures under anaerobic [redox potential (E(h))<-400
      mV] and microaerobic (E(h)= -200 mV) conditions to characterize its energy
      metabolism. Effects of K(+) and Na(+) on growth and metabolism were also
      examined. In a control medium containing 5.2 mM K(+) and 24 mM Na(+), the molar
      growth yield on fructose (Y(fructose)) of microaerobic cultures was 1.3 times
      higher than the yield of anaerobic cultures at D < or =0.10 h(-1), but the
      difference in the Y(fructose) between microaerobic and anaerobic cultures
      decreased at D< or =0.10 h(-1). When the ATP yield from fermentation was
      estimated from the amounts of fructose consumed and acetate formed, the value of
      the microaerobic culture (2.49 mol ATP produced per mol fructose consumed) was
      lower than the anaerobic value [3.13 mol ATP (mol fructose)(-1)]. Therefore, ATP
      production from fermentation could not account for the increase in the
      Y(fructose) at D > 0.10 h(-1) and thus additional ATP was expected to be
      generated via respiration. Assuming that the Y(ATP) (g cells formed per mol ATP
      synthesized) was similar between anaerobic and microaerobic cultures, the
      estimated ATP yield from respiration was between 1.2 and 2.0 mol ATP (mol
      fructose)(-1) below D=0.10 h(-1) and decreased to 0.3 mol ATP (mol fructose)(-1)
      when D was increased to 0.19 h(-1). Such growth-rate-dependent decreases in the
      Y(fructose) and the estimated ATP production from respiration were also observed
      in a high-Na(+) (5.2 mM K(+) and 106 mM Na(+)) culture but not in a high-K(+) (81
      mM K(+) and 24 mM Na(+)) culture. In the high-K(+) culture, the microaerobic
      Y(fructose) was 1.4-2.0 times higher than the anaerobic value and the respiration
      derived ATP yield was estimated to be between 1.2 and 1.9 mol ATP (mol fructose)(
      1) over a wide range of dilution rate. These results suggest that higher
      concentrations of extracellular K(+) are required for the respiration to occur in
      rapidly growing cells of A. actinomycetemcomitans.

PMID- 11535787
TI  - H(2)O(2)-nonproducing Streptococcus pyogenes strains: survival in stationary
      phase and virulence in chronic granulomatous disease.
AB  - The production of hydrogen peroxide (H(2)O(2)) and related phenotypes were
      studied with Streptococcus pyogenes strains isolated from cases of pharyngitis or
      severe group A streptococcal infections. Of the 46 strains examined (34 from
      severe infections and 12 from pharyngitis cases), 25 strains accumulated H(2)O(2)
      in the culture medium when grown under glucose-limited, aerobic conditions,
      whereas the rest of the strains did not. There was no correlation between these
      traits and the type of disease from which each strain had been isolated. The
      H(2)O(2)-nonproducing strains tested in this study belonged to T type 3 or T type
      12. The accumulation of H(2)O(2) started when the culture reached the late
      exponential phase. A rapid loss of cell viability accompanied H(2)O(2)
      accumulation but was completely prevented by the addition of a catalase,
      indicating that the lethality was actually caused by H(2)O(2). Cells of H(2)O(2)
      nonproducing strains were resistant to killing by phagocytes from patients with
      chronic granulomatous disease (CGD), whereas those of H(2)O(2)-producing strains
      were subject to killing. Subcutaneous inoculation of 10(5) c.f.u. H(2)O(2)
      nonproducing S. pyogenes strains into the hind footpads of CGD mice provoked more
      prominent swelling of the footpad than did H(2)O(2)-producing strains. The
      mortality rate in the CGD mice infected with the H(2)O(2)-nonproducing strains
      was higher than that produced by the H(2)O(2)-producing strains. It is suggested
      that H(2)O(2)-nonproducing S. pyogenes strains are prevalent in humans and that
      they may be a potential threat to the health of CGD patients.

PMID- 11535788
TI  - A novel gene encoding a 54 kDa polypeptide is essential for butane utilization by
      Pseudomonas sp. IMT37.
AB  - Twenty-three propane- and butane-utilizing bacteria were isolated from soil
      samples collected from oilfields. Three of them have been identified as
      Rhodococcus sp. IMT35, Pseudomonas sp. IMT37 and Pseudomonas sp. MT40. SDS-PAGE
      analysis of the membrane of Rhodococcus sp. IMT35 revealed the presence of at
      least four polypeptides induced by propane. Polyclonal antibody raised against a
      58 kDa polypeptide from Rhodococcus sp. IMT35 specifically detected bacteria
      which were actively utilizing propane or butane. Immunoscreening of a genomic
      library in lambdagt11 with this antibody resulted in isolation of a clone
      containing a 4.9 kb EcoRI genomic DNA fragment. This 4.9 kb DNA fragment was
      found to hybridize specifically with organisms which could grow on propane or
      butane. This fragment could therefore be used as a probe for detection of such
      bacteria. A 2.3 kb fragment having an ORF encoding a polypeptide of 54 kDa was
      identified by screening a genomic library of Pseudomonas sp. IMT37 with this 4.9
      kb EcoRI fragment. The sequence of the ORF (designated orf54) was found to be
      novel. Primer extension and S1 nuclease mapping showed that transcription of the
      ORF starts at base 283 and it had sequences upstream similar to that of a
      Pseudomonas promoter (-12, -24 type). Disruption of the ORF by a kanamycin
      ('kan') cassette prevented the organism from growing on any alkane but did not
      affect its ability to utilize the respective alkanols and acids, indicating that
      alcohol dehydrogenase and subsequent steps in the pathway remained unaltered. The
      mutants had no detectable level of butane monooxygenase activity. Therefore, the
      product of this gene plays a crucial role in the first step of the pathway and is
      an essential component of monooxygenase. The findings imply that this bacterium
      either employs a common genetic and metabolic route or at least shares the
      product of this gene for utilization of many alkanes.

PMID- 11535789
TI  - Chemotaxis in the human gastric pathogen Helicobacter pylori: different roles for
      CheW and the three CheV paralogues, and evidence for CheV2 phosphorylation.
AB  - The complete genome sequence of Helicobacter pylori has revealed the presence of
      a novel set of chemotaxis genes including three cheV paralogues. CheV is a bi
      functional protein, the N-terminal domain being homologous to the signalling
      complex linker protein CheW, while the C-terminal domain is homologous to the
      response-regulator CheY, but its precise function in chemotaxis is unknown. In
      this study, each of the three cheV paralogues were insertionally inactivated in
      strain 26695 to determine their importance in the chemotactic signal-transduction
      pathway of H. pylori. Mutation of HP0019 (cheV1) had a severe inhibitory effect
      on chemotaxis, as determined by a swarm-plate assay. In contrast, strains
      carrying single mutations in either cheV2 (HP0616) or cheV3 (HP0393) displayed
      wild-type swarming behaviour, as did a cheV2/cheV3 double mutant. However,
      expression of the cheV2 or cheV3 genes in Escherichia coli resulted in an
      inhibition of chemotaxis in a wild-type strain, indicating their role in
      chemotaxis, although these genes were unable to complement isogenic E. coli cheW
      or cheY mutants. The product of cheV2/HP0616 was overexpressed in E. coli and
      purified to homogeneity. Protein fluorescence quenching experiments showed that
      CheV2 was capable of binding acetyl phosphate, a small-molecule phosphodonor. The
      measured K(m) for acetyl phosphate was 21 mM. It is concluded that in the absence
      of a cheZ gene, the CheV proteins could act as phosphate sinks to control the
      cellular level of phospho-CheY in H. pylori. However, only CheV1 was critical for
      chemotaxis, indicating a specific role distinct from the other paralogues in the
      signal-transduction pathway. Significantly, none of the CheV proteins could
      substitute for the loss of CheW, as an H. pylori cheW null mutant was non
      chemotactic.

PMID- 11535790
TI  - Characterization of nirV and a gene encoding a novel pseudoazurin in Rhodobacter
      sphaeroides 2.4.3.
AB  - Sequencing of the region flanking nirK, the gene encoding the copper-containing
      nitrite reductase in Rhodobacter sphaeroides 2.4.3, has identified two genes
      whose products could potentially be involved in nitrite reductase expression and
      activity. One of the genes has been designated nirV. Putative nirV orthologues
      are found in other denitrifiers, where they are also located downstream of the
      structural gene for nitrite reductase. The nirV in 2.4.3 is apparently
      cotranscribed with nirK. Inactivation of nirV had no effect on cell growth, or on
      nitrite reductase expression or activity. Downstream of nirV and divergently
      transcribed is a gene, designated ppaZ, encoding a protein with significant
      similarity to pseudoazurins from other denitrifiers. However, three of the four
      residues required for binding of the type I copper centre are not conserved in
      the deduced sequence of the protein in 2.4.3. ppaZ is expressed only when oxygen
      becomes limiting. ppaZ expression is dependent on both FnrL and NnrR, and a
      putative binding site for these proteins has been identified. Expression of ppaZ
      is also dependent on the two-component PrrB/PrrA system. Inactivation of ppaZ had
      no significant effect on cell growth or on nitrite reductase expression or
      activity. Expression of a maltose-binding protein-PpaZ fusion indicated that the
      protein could not bind copper. Examination of the genome of the related bacterium
      R. sphaeroides 2.4.1 revealed that it encodes ppaZ but not nirV and evidence is
      presented suggesting that a common ancestor of 2.4.3 and 2.4.1 had both nitrite
      and nitric oxide reductase activity but as the strains diverged 2.4.1 lost nirK
      and nirV, making it incapable of nitrite reduction.

PMID- 11535791
TI  - The cep quorum-sensing system of Burkholderia cepacia H111 controls biofilm
      formation and swarming motility.
AB  - Burkholderia cepacia and Pseudomonas aeruginosa often co-exist as mixed biofilms
      in the lungs of patients suffering from cystic fibrosis (CF). Here, the isolation
      of random mini-Tn5 insertion mutants of B. cepacia H111 defective in biofilm
      formation on an abiotic surface is reported. It is demonstrated that one of these
      mutants no longer produces N-acylhomoserine lactones (AHLs) due to an
      inactivation of the cepR gene. cepR and the cepI AHL synthase gene together
      constitute the cep quorum-sensing system of B. cepacia. By using a gene
      replacement method, two defined mutants, H111-I and H111-R, were constructed in
      which cepI and cepR, respectively, had been inactivated. These mutants were used
      to demonstrate that biofilm formation by B. cepacia H111 requires a functional
      cep quorum-sensing system. A detailed quantitative analysis of the biofilm
      structures formed by wild-type and mutant strains suggested that the quorum
      sensing system is not involved in the regulation of initial cell attachment, but
      rather controls the maturation of the biofilm. Furthermore, it is shown that B.
      cepacia is capable of swarming motility, a form of surface translocation utilized
      by various bacteria to rapidly colonize appropriate substrata. Evidence is
      provided that swarming motility of B. cepacia is quorum-sensing-regulated,
      possibly through the control of biosurfactant production. Complementation of the
      cepR mutant H111-R with different biosurfactants restored swarming motility while
      biofilm formation was not significantly increased. This result suggests that
      swarming motility per se is not essential for biofilm formation on abiotic
      surfaces.

PMID- 11535792
TI  - Construction of Rhodococcus random mutagenesis libraries using Tn5 transposition
      complexes.
AB  - The ability to generate tagged mutants of Rhodococcus spp. will facilitate a
      deeper understanding of this medically and commercially important genus. The
      absence of efficient transposon systems in these organisms has here been overcome
      by the use of Tn5-based DNA-protein transposition complexes which can transpose
      at high efficiency. To achieve this, electroporation efficiencies and antibiotic
      selection were optimized. A Rhodococcus rhodochrous CW25 Tn5 insertion library of
      1500 mutants was created. Southern blotting of 23 representative mutants
      demonstrated random insertion. A number of auxotrophic mutants were isolated and
      the disrupted regions involved were identified by inverse PCR and subsequent
      sequencing. Transposition of Tn5 was confirmed by the presence of 9 bp direct
      repeats of Rhodococcus DNA flanking the transposon insertion site. To further
      test this system, a Tn5 insertion library was constructed in a wild-type soil
      isolate of Rhodococcus spp. This is the first viable transposon knockout system
      reported for Rhodococcus.

PMID- 11535793
TI  - Evidence for interfacial uptake in hexadecane degradation by Rhodococcus equi:
      the importance of cell flocculation.
AB  - The kinetics of hexadecane degradation were studied in four strains of
      Rhodococcus equi that did not produce biosurfactants. The aim was to analyse the
      characteristics of alkane uptake and their relevance to a mechanism of
      interfacial uptake. The kinetic studies involved continuous determination of
      degradation by electrolytic respirometry in a diphasic system where the
      hydrophobic phase was hexadecane or a solution of hexadecane in a non-toxic, non
      biodegradable solvent, either 2,2,4,4,6,8,8-heptamethylnonane or silicone oil.
      The technique allowed large variations in interfacial area between the aqueous
      and hydrophobic phases. For the four strains, the kinetics obtained were
      reproducible and showed, in almost all cases, an initial short phase of
      exponential growth, followed by a long phase of linear growth. Specific growth
      rates during exponential growth varied amongst the strains from 0.11 to 0.20 h(
      1) and were independent of interfacial area, in accordance with the very strong
      adsorption of bacterial cells at the interface of solvent and aqueous media. The
      degradation rates during linear growth did not increase with interfacial area but
      increased with efficiency of stirring. These characteristics can be explained by
      the formation of cellular flocs due to the hydrophobicity of the strains. These
      flocs were observed during growth on hexadecane in almost all conditions. In one
      case, with a non-flocculating culture, a kinetic pattern with a longer
      exponential phase, closer to that expected for simple interfacial uptake, was
      observed. The results show that strictly interfacial uptake, limited by floc
      formation (occurring at moderate and higher cell densities, and controlled by
      stirring efficiency) is a common pattern for growth on long-chain alkanes of
      micro-organisms that do not produce biosurfactants.

PMID- 11535794
TI  - The Fbe (SdrG) protein of Staphylococcus epidermidis HB promotes bacterial
      adherence to fibrinogen.
AB  - Staphylococcus epidermidis strains HB and K28 express surface proteins called Fbe
      or SdrG, respectively, that have sequence similarity to the clumping factors ClfA
      and ClfB of Staphylococcus aureus. A mutation in the fbe gene of strain HB was
      isolated by directed plasmid integration using the broad-host-range temperature
      sensitive plasmid pG(+)Host9 (pVE6155). An internal fragment of fbe was cloned
      into pG(+)Host9 and the chimaeric plasmid was mobilized from S. aureus RN4220 to
      S. epidermidis 9142 by conjugation promoted by plasmid pGO1. The plasmid was then
      transferred to S. epidermidis strain HB by phage-48-mediated transduction. The
      plasmid integrated into the chromosomal fbe gene at a frequency of 2.8 x 10(-4).
      All the survivors tested had a copy of pG(+)Host9'fbe' integrated into the
      chromosomal fbe gene either as a single copy or as a tandem array. Western
      immunoblotting showed that the wall-associated Fbe protein was absent in the
      mutant. Wild-type S. epidermidis HB adhered to immobilized fibrinogen in a dose
      dependent and saturable fashion whereas the mutant did not bind. The Fbe proteins
      of HB and K28 were expressed at a high level in Lactococcus lactis MG1363 using
      the expression vector pKS80. These strains adhered strongly to immobilized
      fibrinogen. These results confirm that Fbe is a fibrinogen-binding adhesin.

PMID- 11535795
TI  - Evidence for redundancy in cysteine biosynthesis in Rhizobium leguminosarum
      RL3841: analysis of a cysE gene encoding serine acetyltransferase.
AB  - A cysE gene encoding a serine acetyltransferase (SAT) potentially involved in the
      biosynthesis of cysteine was identified approximately 4 kb upstream of the
      previously described aapJQMP gene cluster that encodes an amino acid permease in
      Rhizobium leguminosarum strain 3841. The gene exhibits >40% identity to the
      family of SATs containing N-terminal extensions that have been described for
      other bacteria and plants. The ORF has three possible translation initiation
      sites which potentially encode polypeptides of 311, 277 and/or 259 amino acid
      residues, respectively. All three ORFs complemented the cysE mutation in an
      Escherichia coli cysteine auxotroph, strain JM39. Insertion of Tn5-lacZ into cysE
      in the genome of R. leguminosarum (strain RU632) lowered SAT activity in crude
      extracts by >95%. However, RU632 was not a cysteine auxotroph, which suggests
      that R. leguminosarum possesses some redundancy in cysteine biosynthesis.
      Additional copies of cysE could not be detected in the genome when the R.
      leguminosarum cysE gene was used as a hybridization probe. Therefore it is
      possible that R. leguminosarum possesses an alternative pathway for cysteine
      biosynthesis which avoids O-acetylserine. Strain RU632 was unaffected in its
      ability to nodulate Pisum sativum, and the nodules were effective for N(2)
      fixation (measured by C(2)H(2) reduction). Transcriptional activity of cysE was
      determined by measuring the beta-galactosidase arising from cysE::Tn5-lacZ
      fusions. Maximal levels of expression were observed during early exponential
      growth and were not influenced by the level of sulphur (supplied as sulphate).
      However, transcription was repressed by approximately twofold in ammonium-grown,
      as opposed to glutamate-grown, cultures. Repression by ammonium was not seen in a
      strain defective for ntrC.

PMID- 11535796
TI  - The penicillin resistance of Enterococcus faecalis JH2-2r results from an
      overproduction of the low-affinity penicillin-binding protein PBP4 and does not
      involve a psr-like gene.
AB  - A penicillin-resistant mutant, JH2-2r (MIC 75 microg ml(-1)), was isolated from
      Enterococcus faecalis JH2-2 (MIC 5 microg ml(-1)) by successive passages on
      plates containing increasing concentrations of benzylpenicillin. A comparison of
      the penicillin-binding protein (PBP) profiles in the two strains revealed a more
      intensely labelled PBP4 in JH2-2r. Because the sequences of the JH2-2 and JH2-2r
      pbp4 genes were strictly identical, even in their promoter regions, this
      intensive labelling could only be associated with an overproduction of the low
      affinity PBP4. No psr gene analogous to that proposed to act as a regulator of
      PBP5 synthesis in Enterococcus hirae and Enterococcus faecium could be identified
      in the vicinity of pbp4 in E. faecalis JH2-2 and JH2-2r. However, a psr-like gene
      distant from pbp4 was identified. The cloning and sequencing of that psr-like
      gene from both E. faecalis strains indicated that they were identical. It is
      therefore postulated that the PBP4 overproduction in E. faecalis JH2-2r results
      from the modification of an as yet unidentified factor.

PMID- 11535797
TI  - The VanY(D) DD-carboxypeptidase of Enterococcus faecium BM4339 is a penicillin
      binding protein.
AB  - VanD-type Enterococcus faecium BM4339 is constitutively resistant to vancomycin
      and to low levels of teicoplanin. This strain produces peptidoglycan precursors
      terminating in D-lactate but, unlike VanA- and VanB-type strains, E. faecium
      BM4339 has a mutated ddl ligase gene and cannot synthesize D-Ala-D-Ala.
      Consequently, although it possesses vanX(D) and vanY(D) genes, it should not
      require an active VanX-type DD-dipeptidase or a VanY-type DD-carboxypeptidase for
      resistance. The vanY(D) gene contains the signatures of a penicillin-binding
      protein (PBP) and is believed to encode a penicillin-sensitive DD
      carboxypeptidase. The enzyme activity was found to be membrane-bound and
      inhibited by low concentrations of benzylpenicillin in membrane preparations and
      in intact bacteria, indicating that the active site was present on the outside
      surface of the membrane. The 38 kDa protein was revealed as a PBP present in more
      copies per cell than conventional PBPs and all the protein was accessible to
      benzylpenicillin added externally, confirming the localization of the active
      site. A glycopeptide-susceptible strain of E. faecium lacked this PBP, and the
      membrane-bound DD-carboxypeptidase activity was less than 5% of that of E.
      faecium BM4339. Although the active site of VanY(D) was external to the membrane,
      UDP-MurNAc-tetrapeptide was produced internally, probably from UDP-MurNAc
      pentadepsipeptide. The presence of benzylpenicillin at low concentrations in the
      growth medium substantially reduced the amount of tetrapeptide produced,
      indicating that inhibition of VanY(D) by benzylpenicillin influenced production
      of peptidoglycan precursors internally. A model to explain these contrasting
      observations is proposed.

PMID- 11535798
TI  - Glyceraldehyde-3-phosphate dehydrogenase is negatively regulated by ADP
      ribosylation in the fungus Phycomyces blakesleeanus.
AB  - Dormant spores of Phycomyces blakesleeanus contain a 37 kDa protein that is
      endogenously mono-ADP-ribosylated. This protein was purified and identified as
      glyceraldehyde-3-phosphate dehydrogenase (GAPDH) by N-terminal sequencing and
      homology analysis. GAPDH enzymic activity changed dramatically upon spore
      germination, being maximal at stages where ADP-ribosylation was nearly
      undetectable. The presence of glyceraldehyde 3-phosphate in this reaction
      affected the [(32)P]ADP-ribosylation of the GAPDH. ADP-ribosylation of the GAPDH
      occurred by transfer of the ADP-ribose moiety from NAD to an arginine residue. A
      model for the regulation of GAPDH activity and its role in spore germination in
      P. blakesleeanus is proposed.

PMID- 11535799
TI  - Reintroduction of the PLB1 gene into Candida albicans restores virulence in vivo.
AB  - Phospholipases have been proposed to contribute to the virulence of Candida
      albicans. Recently, a candidal strain deleted for PLB1, the gene encoding the
      predominant phospholipase B (Plb1) secreted by C. albicans, was constructed and
      its virulence in an intravenous murine model of disseminated candidiasis was
      evaluated. In the present study, the PLB1 gene was reintroduced back into the
      plb1 null mutant to generate the revertant strain, which showed similar growth
      and morphology to its isogenic parent strain. Virulence of the revertant strain
      was found to be comparable to that of the parent strain in an intravenous murine
      model of disseminated candidiasis. To compare the abilities of the plb1 null
      mutant, the revertant and the isogenic parent strains to cross the
      gastrointestinal (GI) tract and cause systemic infection, an oral-intragastric
      infant mouse model of candidiasis was used. Histological examinations and
      analysis of c.f.u. of the pathogen in liver homogenates revealed that the
      parental and revertant strains were able to invade and traverse the GI mucosa to
      a significantly greater extent than the plb1 null mutant. Immunofluorescence and
      immunoelectron microscopic studies of infected host tissue using anti-Plb1
      antibody showed that Plb1 is secreted during invasion of the gastric mucosa by
      the parental and revertant strains. In contrast, little or no labelling was
      observed in the null mutant strain. The results indicate that the Plb1 secreted
      by C. albicans enhances the ability of this organism to cross the GI tract and
      disseminate haematogenously. These studies provide unequivocal evidence
      supporting a role for Plb1 during the course of infection by C. albicans.

PMID- 11535800
TI  - Phylogeny of the genus Haemophilus as determined by comparison of partial infB
      sequences.
AB  - A 453 bp fragment of infB, the gene encoding translation initiation factor 2, was
      sequenced and compared from 66 clinical isolates and type strains of Haemophilus
      species and related bacteria. Analysis of the partial infB sequences obtained
      suggested that the human isolates dependent on X and V factor, H. influenzae, H.
      haemolyticus, H. aegyptius and some cryptic genospecies of H. influenzae, were
      closely related to each other. H. parainfluenzae constituted a heterogeneous
      group within the boundaries of the genus, whereas H. aphrophilus/paraphrophilus
      and Actinobacillus actinomycetemcomitans were only remotely related to the type
      species of the genus Haemophilus H. parahaemolyticus and H. paraphrohaemolyticus
      took up an intermediary position and may not belong in the genus Haemophilus
      sensu stricto. Ambiguous results were obtained with seven isolates tentatively
      identified as H. segnis, which fell into two discrete clusters. The delineation
      of 'Haemophilus sensu stricto' as suggested by infB analysis supports previous
      results obtained by DNA hybridization, in contrast to the delineation inferred
      from 16S rRNA sequence comparison.

PMID- 11535801
TI  - The use of signature sequences in different proteins to determine the relative
      branching order of bacterial divisions: evidence that Fibrobacter diverged at a
      similar time to Chlamydia and the Cytophaga-Flavobacterium-Bacteroides division.
AB  - The phylogenetic placement of the rumen bacterium Fibrobacter succinogenes was
      determined using a signature sequence approach that allows determination of the
      relative branching order of the major divisions among Bacteria [Gupta, R. S.
      (2000) FEMS Microbiol Rev 24, 367-402]. For this purpose, segments of the Hsp60
      (groEL), Hsp70 (dnaK), CTP synthase and alanyl-tRNA synthetase genes, which are
      known to contain signature sequences that are useful for phylogenetic
      deterministic purposes, were cloned. Using degenerate oligonucleotide primers for
      highly conserved regions in these proteins, 1.4 kb, 0.75 kb, 401 bp and 171 bp
      fragments of the Hsp70, Hsp60, CTP synthase and alanyl-tRNA synthetase genes
      respectively were amplified by PCR, and these fragments were cloned and
      sequenced. These primers, because of their high degree of conservation, could
      also be used for cloning these genes from other bacterial species. The Hsp70
      homologues from different Gram-negative bacteria contain a 21-23 aa insert that
      is not found in any Gram-positive bacteria. The presence of this insert in the F.
      succinogenes Hsp70 supports its placement within the Gram-negative group of
      bacteria. A conserved insert in F. succinogenes Hsp60 that is commonly present in
      all bacterial species, except various Gram-positive bacteria, Deinococcus-Thermus
      groups and green non-sulphur bacteria, provides evidence that F. succinogenes
      does not belong to these taxa. A particularly useful signature consisting of a 4
      aa insert is found in Ala-tRNA synthetase. This insert is present in all
      proteobacterial homologues as well as in homologues from species belonging to the
      Chlamydia and Cytophaga-Flavobacterium- Bacteroides (CFB) groups, but it is not
      found in homologues from any other groups of bacteria. The presence of this
      insert in F. succinogenes Ala-tRNA synthetase provides evidence that this species
      is related to these groups. However, two other signatures in CTP synthase and
      Hsp70 proteins, that are distinctive of the proteobacterial species, are not
      present in the F. succinogenes homologues. These results provide evidence that F.
      succinogenes does not belong to the proteobacterial division and thus should be
      placed in a similar position as the Chlamydia and CFB groups of species.

PMID- 11535802
TI  - Inhibitory effect of aflastatin A on melanin biosynthesis by Colletotrichum
      lagenarium.
AB  - The effect of aflastatin A (AsA), a novel inhibitor of aflatoxin production, on
      melanin biosynthesis of Colletotrichum lagenarium was examined. Addition of a low
      concentration of AsA (0.5 microg ml(-1)) to the culture medium almost completely
      inhibited the melanin production of this organism. AsA also inhibited the
      production of scytalone, an early intermediate of melanin biosynthesis. Melanin
      production was restored by addition of exogenous scytalone in the presence of
      AsA, suggesting that the late steps after the synthesis of scytalone were not
      significantly affected by AsA. This was confirmed by the results from RT-PCR
      analysis of the expression of genes encoding melanin biosynthetic enzymes (SCD1,
      THR1) and a regulatory gene (CMR1). By contrast, expression of PKS1 was severely
      impaired by AsA, although catalytic activity of a polyketide synthase (PKS1) was
      not inhibited by AsA. These results indicate that AsA inhibits an early step in
      melanin production, which suppresses the expression of PKS1.

PMID- 11535803
TI  - Phenotypic diversity and ecosystem functioning in changing environments: a
      theoretical framework.
AB  - Biodiversity plays a vital role for ecosystem functioning in a changing
      environment. Yet theoretical approaches that incorporate diversity into classical
      ecosystem theory do not provide a general dynamic theory based on mechanistic
      principles. In this paper, we suggest that approaches developed for quantitative
      genetics can be extended to ecosystem functioning by modeling the means and
      variances of phenotypes within a group of species. We present a framework that
      suggests that phenotypic variance within functional groups is linearly related to
      their ability to respond to environmental changes. As a result, the long-term
      productivity for a group of species with high phenotypic variance may be higher
      than for the best single species, even though high phenotypic variance decreases
      productivity in the short term, because suboptimal species are present. In
      addition, we find that in the case of accelerating environmental change, species
      succession in a changing environment may become discontinuous. Our work suggests
      that this phenomenon is related to diversity as well as to the environmental
      disturbance regime, both of which are affected by anthropogenic activities. By
      introducing new techniques for modeling the aggregate behavior of groups of
      species, the present approach may provide a new avenue for ecosystem analysis.

PMID- 11535804
TI  - Compaction of single DNA molecules induced by binding of integration host factor
      (IHF).
AB  - We studied the interaction between the integration host factor (IHF), a major
      nucleoid-associated protein in bacteria, and single DNA molecules. Force
      extension measurements of lambda DNA and an analysis of the Brownian motion of
      small beads tethered to a surface by single short DNA molecules, in equilibrium
      with an IHF solution, indicate that: (i) the DNA-IHF complex retains a random,
      although more compact, coiled configuration for zero or small values of the
      tension, (ii) IHF induces DNA compaction by binding to multiple DNA sites with
      low specificity, and (iii) with increasing tension on the DNA, the elastic
      properties of bare DNA are recovered. This behavior is consistent with the
      predictions of a statistical mechanical model describing how proteins bending DNA
      are driven off by an applied tension on the DNA molecule. Estimates of the amount
      of bound IHF in DNA-IHF complexes obtained from the model agree very well with
      independent measurements of this quantity obtained from the analysis of DNA-IHF
      crosslinking. Our findings support the long-held view that IHF and other histone
      like proteins play an important role in shaping the long-scale structure of the
      bacterial nucleoid.

PMID- 11535805
TI  - History dependence of protein adsorption kinetics.
AB  - The behavior of proteins at biological and synthetic interfaces is often
      characterized by a strong history dependence caused by long relaxation times or
      irreversible transitions. In this work, we introduce the rate of adsorption as a
      means to systematically quantify the extent, and identify the underlying causes,
      of history dependence. We use multistep kinetic experiments in which the i'th
      step is an exposure of a Si(Ti)O(2) surface to a flowing fibronectin or
      cytochrome c solution of concentration c(i) for a time t(i) (c(i) = 0 corresponds
      to a rinse) and measure the protein adsorption by optical waveguide light mode
      spectroscopy. The rate of adsorption is sensitive to the structure of the
      adsorbed layer, and we observe it to greatly increase, for a given adsorbed
      density, when going from a first to a subsequent adsorption step. This increase
      is most pronounced when the duration of the initial adsorption step is long. We
      attribute these observations to the gradual and irreversible formation of protein
      clusters or locally ordered structures and use them to explain previous
      underestimates of kinetic data by mesoscopic model descriptions. A thorough
      understanding of these complex postadsorption events, and their impact on history
      dependence, is essential for many physiological and biotechnological processes.
      Optical waveguide lightmode spectroscopy is a promising technique for their
      macroscopic quantification.

PMID- 11535806
TI  - Effect of spermidine on the in vivo degradation of ornithine decarboxylase in
      Saccharomyces cerevisiae.
AB  - As part of our studies on the regulation of polyamine biosynthesis in
      Saccharomyces cerevisiae, we have investigated the effect of spermidine on the
      degradation of ornithine decarboxylase in this organism. We have found that in S.
      cerevisiae, as in other eukaryotic cells, the rate of degradation of ornithine
      decarboxylase, measured either enzymatically or immunologically, is increased by
      the addition of spermidine to a yeast culture. It is noteworthy that this effect
      of added spermidine is found even when the experiments are conducted with strains
      in which the ornithine decarboxylase is overexpressed several hundred-fold more
      than the wild-type level. The effect of added spermidine in the overexpressed
      SPE1 strains is best seen in spe2 mutants in which the initial intracellular
      spermidine is very low or absent. Experiments with cycloheximide show that new
      protein synthesis is required to effect the breakdown of the ornithine
      decarboxylase. These results indicate that S. cerevisiae contains an antizyme
      like mechanism for the control of the level of ornithine decarboxylase by
      spermidine, even though, as contrasted with other eukaryotic cells, no specific
      antizyme homologue has been detected either in in vitro experiments or in the S.
      cerevisiae genome.

PMID- 11535807
TI  - Local uncaging of caged Ca(2+) reveals distribution of Ca(2+)-activated Cl(-)
      channels in pancreatic acinar cells.
AB  - In exocrine acinar cells, Ca(2+)-activated Cl(-) channels in the apical membrane
      are essential for fluid secretion, but it is unclear whether such channels are
      important for Cl(-) uptake at the base. Whole-cell current recording, combined
      with local uncaging of caged Ca(2+), was used to reveal the Cl(-) channel
      distribution in mouse pancreatic acinar cells, where approximately 90% of the
      current activated by Ca(2+) in response to acetylcholine was carried by Cl(-).
      When caged Ca(2+) in the cytosol was uncaged locally in the apical pole, the Cl(
      ) current was activated, whereas local Ca(2+) uncaging in the basal or lateral
      areas of the cell had no effect. Even when Ca(2+) was uncaged along the whole
      inner surface of the basolateral membrane, no Cl(-) current was elicited. There
      was little current deactivation at a high cytosolic Ca(2+) concentration
      ([Ca(2+)](c)), but at a low [Ca(2+)](c) there was clear voltage-dependent
      deactivation, which increased with hyperpolarization. Functional Ca(2+)-activated
      Cl(-) channels are expressed exclusively in the apical membrane and channel
      opening is strictly regulated by [Ca(2+)](c) and membrane potential. Ca(2+)
      activated Cl(-) channels do not mediate Cl(-) uptake at the base, but
      acetylcholine-elicited local [Ca(2+)](c) spiking in the apical pole can regulate
      fluid secretion by controlling the opening of these channels in the apical
      membrane.

PMID- 11535808
TI  - Correspondence analysis applied to microarray data.
AB  - Correspondence analysis is an explorative computational method for the study of
      associations between variables. Much like principal component analysis, it
      displays a low-dimensional projection of the data, e.g., into a plane. It does
      this, though, for two variables simultaneously, thus revealing associations
      between them. Here, we demonstrate the applicability of correspondence analysis
      to and high value for the analysis of microarray data, displaying associations
      between genes and experiments. To introduce the method, we show its application
      to the well-known Saccharomyces cerevisiae cell-cycle synchronization data by
      Spellman et al. [Spellman, P. T., Sherlock, G., Zhang, M. Q., Iyer, V. R.,
      Anders, K., Eisen, M. B., Brown, P. O., Botstein, D. & Futcher, B. (1998) Mol.
      Biol. Cell 9, 3273-3297], allowing for comparison with their visualization of
      this data set. Furthermore, we apply correspondence analysis to a non-time-series
      data set of our own, thus supporting its general applicability to microarray data
      of different complexity, underlying structure, and experimental strategy (both
      two-channel fluorescence-tag and radioactive labeling).

PMID- 11535809
TI  - Suppression of Ras-mediated tumorigenicity and metastasis through inhibition of
      the Met receptor tyrosine kinase.
AB  - Mutations in the Ras family of GTP binding proteins represent one of the most
      frequently observed genetic alterations in human cancers. We and others have
      recently demonstrated that expression of Met, the tyrosine kinase receptor for
      hepatocyte growth factor/scatter factor (HGF/SF), is significantly up-regulated
      in Ras-transformed cells. Because HGF/SF-Met signaling is proposed to play a
      prominent role in tumor development and progression, we assessed the possible
      requirement for Met during Ras-mediated tumor growth and metastasis. To disrupt
      endogenous Met signaling, we constructed dominant-negative mutants of both human
      and murine Met and showed that these can inhibit HGF/SF-mediated Met signaling
      and cell invasion of ras-transformed cells in vitro. Moreover, ectopic expression
      of dominant-negative Met mutants reduced the s.c. tumor growth of ras-transformed
      cells and dramatically suppressed their ability to form lung metastases in vivo.
      Our data demonstrate that Met plays a prominent role during Ras-mediated tumor
      growth and metastasis, and further suggest that agents that inhibit HGF/SF-Met
      signaling may represent an important therapeutic avenue for the treatment of a
      variety of malignant tumors.

PMID- 11535810
TI  - An AAV-derived Apaf-1 dominant negative inhibitor prevents MPTP toxicity as
      antiapoptotic gene therapy for Parkinson's disease.
AB  - Adeno-associated virus (AAV) vector delivery of an Apaf-1-dominant negative
      inhibitor was tested for its antiapoptotic effect on degenerating nigrostriatal
      neurons in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of
      Parkinson's disease. The wild-type caspase recruitment domain of Apaf-1 was used
      as a dominant negative inhibitor of Apaf-1 (rAAV-Apaf-1-DN-EGFP). An AAV virus
      vector was used to deliver it into the striatum of C57 black mice, and the
      animals were treated with MPTP. The number of tyrosine hydroxylase-positive
      neurons in the substantia nigra was not changed on the rAAV-Apaf-1-DN-EGFP
      injected side compared with the noninjected side. We also examined the effect of
      a caspase 1 C285G mutant as a dominant negative inhibitor of caspase 1 (rAAV
      caspase-1-DN-EGFP) in the same model. However, there was no difference in the
      number of tyrosine hydroxylase-positive neurons between the rAAV-caspase-1-DN
      EGFP injected side and the noninjected side. These results indicate that delivery
      of Apaf-1-DN by using an AAV vector system can prevent nigrostriatal degeneration
      in MPTP mice, suggesting that it could be a promising therapeutic strategy for
      patients with Parkinson's disease. The major mechanism of dopaminergic neuronal
      death triggered by MPTP seems to be the mitochondrial apoptotic pathway.

PMID- 11535811
TI  - Crystal structure of the human CD4 N-terminal two-domain fragment complexed to a
      class II MHC molecule.
AB  - The structural basis of the interaction between the CD4 coreceptor and a class II
      major histocompatibility complex (MHC) is described. The crystal structure of a
      complex containing the human CD4 N-terminal two-domain fragment and the murine I
      A(k) class II MHC molecule with associated peptide (pMHCII) shows that only the
      "top corner" of the CD4 molecule directly contacts pMHCII. The CD4 Phe-43 side
      chain extends into a hydrophobic concavity formed by MHC residues from both alpha
      2 and beta 2 domains. A ternary model of the CD4-pMHCII-T-cell receptor (TCR)
      reveals that the complex appears V-shaped with the membrane-proximal pMHCII at
      the apex. This configuration excludes a direct TCR-CD4 interaction and suggests
      how TCR and CD4 signaling is coordinated around the antigenic pMHCII complex.
      Human CD4 binds to HIV gp120 in a manner strikingly similar to the way in which
      CD4 interacts with pMHCII. Additional contacts between gp120 and CD4 give the CD4
      gp120 complex a greater affinity. Thus, ligation of the viral envelope
      glycoprotein to CD4 occludes the pMHCII-binding site on CD4, contributing to
      immunodeficiency.

PMID- 11535812
TI  - Distinct effects of cAMP and mitogenic signals on CREB-binding protein
      recruitment impart specificity to target gene activation via CREB.
AB  - Ser-133 phosphorylation of the cAMP-responsive element-binding protein (CREB) is
      sufficient to induce cellular gene expression in response to cAMP, but additional
      promoter-bound factors are required for target gene activation by CREB in
      response to mitogen/stress signals. To compare the relative effects of different
      signals on recruitment of the coactivator CREB-binding protein (CBP) to CREB in
      living cells, we developed a fluorescence resonance energy transfer (FRET) assay.
      cAMP promoted the interaction of CREB with CBP in a phosphorylation-dependent
      manner by FRET analysis, but mitogen/stress signals were far less effective in
      stimulating complex formation even though they induced comparable levels of Ser
      133 phosphorylation. cAMP and non-cAMP stimuli were comparably active in
      promoting this interaction in the cytosol; the formation of CREB x CBP complexes
      in response to non-cAMP signals was specifically inhibited in the nucleus. Non
      cAMP signals had no effect on intrinsic CREB- or CBP-binding activities by Far
      Western blot assay, thereby supporting the presence of a distinct CREB x CBP
      antagonist. Our studies indicate that the relative effects of cAMP and
      mitogen/stress signals on CREB x CBP complex formation impart selectivity to gene
      activation through CREB phosphorylated at Ser-133.

PMID- 11535813
TI  - Searching sequence space for protein catalysts.
AB  - Genetic selection was used to explore the probability of finding enzymes in
      protein sequence space. Large degenerate libraries were prepared by replacing all
      secondary structure units in a dimeric, helical bundle chorismate mutase with
      simple binary-patterned modules based on a limited set of four polar and four
      nonpolar residues. Two-stage in vivo selection yielded catalytically active
      variants possessing biophysical and kinetic properties typical of the natural
      enzyme even though approximately 80% of the protein originates from the
      simplified modules and >90% of the protein consists of only eight different amino
      acids. This study provides a quantitative assessment of the number of sequences
      compatible with a given fold and implicates previously unidentified residues
      needed to form a functional active site. Given the extremely low incidence of
      enzymes in completely unbiased libraries, strategies that combine chemical
      information with genetic selection, like the one used here, may be generally
      useful in designing novel protein scaffolds with tailored activities.

PMID- 11535814
TI  - Partitioning of Thy-1, GM1, and cross-linked phospholipid analogs into lipid
      rafts reconstituted in supported model membrane monolayers.
AB  - As shown earlier, raft-like domains resembling those thought to be present in
      natural cell membranes can be formed in supported planar lipid monolayers. These
      liquid-ordered domains coexist with a liquid-disordered phase and form in
      monolayers prepared both from synthetic lipid mixtures and lipid extracts of the
      brush border membrane of mouse kidney cells. The domains are detergent-resistant
      and are highly enriched in the glycosphingolipid GM1. In this work, the
      properties of these raft-like domains are further explored and compared with
      properties thought to be central to raft function in plasma membranes. First, it
      is shown that domain formation and disruption critically depends on the
      cholesterol density and can be controlled reversibly by treating the monolayers
      with the cholesterol-sequestering reagent methyl-beta-cyclodextrin. Second, the
      glycosylphosphatidylinositol-anchored cell-surface protein Thy-1 significantly
      partitions into the raft-like domains. The extent of this partitioning is reduced
      when the monolayers contain GM1, indicating that different molecules can compete
      for domain occupation. Third, the partitioning of a saturated phospholipid analog
      into the raft phase is dramatically increased (15% to 65%) after cross-linking
      with antibodies, whereas the distribution of a doubly unsaturated phospholipid
      analog is not significantly affected by cross-linking (approximately 10%). This
      result demonstrates that cross-linking, a process known to be important for
      certain cell-signaling processes, can selectively translocate molecules to liquid
      ordered domains.

PMID- 11535815
TI  - Replication of enhancer-deficient amphotropic murine leukemia virus in human
      cells.
AB  - Amphotropic murine leukemia virus (MLV) replicates in cells from various
      mammalian species, including humans, and is a potential contaminant in MLV vector
      preparations for human gene transfer studies. The generation of replication
      competent virus is considered less likely with vectors that delete the viral
      transcription elements. This conclusion is based on data obtained in rodents,
      where MLV replication depends on the expression of viral genes under the control
      of 75-bp enhancer elements in the long terminal repeat. We demonstrate here that
      in some human cells replication of amphotropic MLV is possible in the absence of
      these enhancer elements. Replication of the enhancer-deficient virus MLV
      (MOA)Delta E is observed in selected human sarcoma and B lymphoma lines and
      proceeds at a lower rate than that of the intact virus. No insertion of a foreign
      promoter or enhancer into the long terminal repeat was detected. Our data suggest
      the presence of a secondary enhancer element within the MLV provirus that can in
      selected human cells mediate virus transcription and replication in the absence
      of the 75-bp U3 enhancers.

PMID- 11535816
TI  - Quinine blocks specific gap junction channel subtypes.
AB  - We demonstrate that the antimalarial drug quinine specifically reduces currents
      through gap junctions formed by some connexins (Cx) in transfected mammalian
      cells, but does not affect other gap junction types. Quinine blocked Cx36 and
      Cx50 junctional currents in a reversible and concentration-dependent manner with
      half maximal blocking concentrations of 32 and 73 microM, respectively; Hill
      coefficients for block by quinine were about 2 for both connexins. In contrast,
      quinine did not substantially block gap junction channels formed by Cx26, Cx32,
      Cx40, and Cx43, and only moderately affected Cx45 junctions. To determine the
      location of the binding site of quinine (pKa = 8.7), we investigated the effect
      of quinine at various external and internal pH values and the effect of a
      permanently charged quaternary derivative of quinine. Our results indicate that
      the binding site for quinine is intracellular, possibly within the pore. Single
      channel studies indicated that exposure to quinine induced slow transitions
      between open and fully closed states that decreased open probability of the
      channel. Quinine thus offers a potentially useful method to block certain types
      of gap junction channels, including those between neurons that are formed by
      Cx36. Moreover, quinine derivatives that are excluded from other types of
      membrane channels may provide molecules with connexin-specific as well as
      connexin-selective blocking activity.

PMID- 11535817
TI  - The histone deacetylase inhibitor and chemotherapeutic agent suberoylanilide
      hydroxamic acid (SAHA) induces a cell-death pathway characterized by cleavage of
      Bid and production of reactive oxygen species.
AB  - Many chemotherapeutic agents induce mitochondrial-membrane disruption to initiate
      apoptosis. However, the upstream events leading to drug-induced mitochondrial
      perturbation have remained poorly defined. We have used a variety of
      physiological and pharmacological inhibitors of distinct apoptotic pathways to
      analyze the manner by which suberoylanilide hydroxamic acid (SAHA), a
      chemotherapeutic agent and histone deacetylase inhibitor, induces cell death. We
      demonstrate that SAHA initiates cell death by inducing mitochondria-mediated
      death pathways characterized by cytochrome c release and the production of
      reactive oxygen species, and does not require the activation of key caspases such
      as caspase-8 or -3. We provide evidence that mitochondrial disruption is achieved
      by means of the cleavage of the BH3-only proapoptotic Bcl-2 family member Bid.
      SAHA-induced Bid cleavage was not blocked by caspase inhibitors or the
      overexpression of Bcl-2 but did require the transcriptional regulatory activity
      of SAHA. These data provide evidence of a mechanism of cell death mediated by
      transcriptional events that result in the cleavage of Bid, disruption of the
      mitochondrial membrane, and production of reactive oxygen species to induce cell
      death.

PMID- 11535818
TI  - Cardiomyocytes induce endothelial cells to trans-differentiate into cardiac
      muscle: implications for myocardium regeneration.
AB  - The concept of tissue-restricted differentiation of postnatal stem cells has been
      challenged by recent evidence showing pluripotency for hematopoietic,
      mesenchymal, and neural stem cells. Furthermore, rare but well documented
      examples exist of already differentiated cells in developing mammals that change
      fate and trans-differentiate into another cell type. Here, we report that
      endothelial cells, either freshly isolated from embryonic vessels or established
      as homogeneous cells in culture, differentiate into beating cardiomyocytes and
      express cardiac markers when cocultured with neonatal rat cardiomyocytes or when
      injected into postischemic adult mouse heart. Human umbilical vein endothelial
      cells also differentiate into cardiomyocytes under similar experimental
      conditions and transiently coexpress von Willebrand factor and sarcomeric myosin.
      In contrast, neural stem cells, which efficiently differentiate into skeletal
      muscle, differentiate into cardiomyocytes at a low rate. Fibroblast growth factor
      2 and bone morphogenetic protein 4, which activate cardiac differentiation in
      embryonic cells, do not activate cardiogenesis in endothelial cells or stimulate
      trans-differentiation in coculture, suggesting that different signaling molecules
      are responsible for cardiac induction during embryogenesis and in successive
      periods of development. The fact that endothelial cells can generate
      cardiomyocytes sheds additional light on the plasticity of endothelial cells
      during development and opens perspectives for cell autologous replacement
      therapies.

PMID- 11535820
TI  - Water clusters: untangling the mysteries of the liquid, one molecule at a time.
AB  - Extensive terahertz laser vibration-rotation-tunneling spectra and mid-IR laser
      spectra have been compiled for several isotopomers of small (dimer through
      hexamer) water clusters. These data, in conjunction with new theoretical
      advances, quantify the structures, force fields, dipole moments, and hydrogen
      bond rearrangement dynamics in these clusters. This new information permits us to
      systematically untangle the intricacies associated with cooperative hydrogen
      bonding and promises to lead to a more complete molecular description of the
      liquid and solid phases of water, including an accurate universal force field.

PMID- 11535819
TI  - Prostatic intraepithelial neoplasia in mice expressing an androgen receptor
      transgene in prostate epithelium.
AB  - Prostate cancer (PCa) is an androgen dependent disease that can be treated by
      androgen ablation therapy, and clinical trials are under way to prevent PCa
      through the reduction of androgen receptor (AR) activity. However, there are no
      animal models of AR-mediated prostatic neoplasia, and it remains unclear whether
      the AR is a positive or negative regulator of cell growth in normal prostate
      secretory epithelium. To assess the direct effects of the AR in prostate
      epithelium, a murine AR transgene regulated by the rat probasin promoter (Pb) was
      used to generate transgenic mice expressing increased levels of AR protein in
      prostate secretory epithelium. The prostates in younger (<1 year) Pb-mAR
      transgenic mice were histologically normal, but Ki-67 immunostaining revealed
      marked increases in epithelial proliferation in ventral prostate and dorsolateral
      prostate. Older (>1 year) transgenic mice developed focal areas of
      intraepithelial neoplasia strongly resembling human high-grade prostatic
      intraepithelial neoplasia (PIN), a precursor to PCa. These results demonstrate
      that the AR is a positive regulator of cell growth in normal prostate epithelium
      and provide a model system of AR-stimulated PIN that can be used for assessing
      preventative hormonal therapies and for identifying secondary transforming events
      relevant to human PCa.

PMID- 11535821
TI  - Identification of a new malaria susceptibility locus (Char4) in recombinant
      congenic strains of mice.
AB  - The genetic component of susceptibility to malaria is complex, both in humans and
      in the mouse model of infection. Two murine loci on chromosomes 8 (Pchr/Char2)
      and 9 (Char1) have previously been mapped in F(2) crosses, and play an important
      role in regulating blood parasitemia and survival to infection with Plasmodium
      chabaudi. These loci explain only part of the interstrain phenotypic variance,
      and their penetrance and expressivity vary in different inbred strains. Novel
      loci regulating response to P. chabaudi infection were investigated by using an
      alternative strategy based on a newly derived set of AcB/BcA recombinant congenic
      strains bred from malaria-susceptible A/J (A) and resistant C57BL/6J (B6). One of
      the AcB strains, AcB55, is shown to be highly resistant to infection despite 83%
      susceptible A genomic composition, including susceptibility alleles at Char1 and
      Pchr/Char2. Early onset of parasite clearance in AcB55 is associated with lower
      peak parasitemia and absence of mortality. Linkage analysis in an informative
      (AcB55 x A)F(2) population, using peak parasitemia as a quantitative trait,
      located a new B6-derived resistance locus on chromosome 3 (lod score = 6.57) that
      we designate Char4. A second, suggestive linkage on chromosome 10 (lod score =
      2.53) shows additive effect with Char4 on peak parasitemia. Char4 maps to a small
      congenic B6 fragment in AcB55 that should facilitate the search for candidate
      genes. Our findings provide an entry point for parallel association studies in
      humans between the syntenic 4q21-4q25 region and susceptibility to disease in
      endemic areas of malaria.

PMID- 11535822
TI  - Genomic profiling of short- and long-term caloric restriction effects in the
      liver of aging mice.
AB  - We present genome-wide microarray expression analysis of 11,000 genes in an aging
      potentially mitotic tissue, the liver. This organ has a major impact on health
      and homeostasis during aging. The effects of life- and health-span-extending
      caloric restriction (CR) on gene expression among young and old mice and between
      long-term CR (LT-CR) and short-term CR (ST-CR) were examined. This experimental
      design allowed us to accurately distinguish the effects of aging from those of CR
      on gene expression. Aging was accompanied by changes in gene expression
      associated with increased inflammation, cellular stress, and fibrosis, and
      reduced capacity for apoptosis, xenobiotic metabolism, normal cell-cycling, and
      DNA replication. LT-CR and just 4 weeks of ST-CR reversed the majority of these
      changes. LT-CR produced in young mice a pattern of gene expression that is a
      subset of the changes found in old LT-CR mice. It is possible that the early
      changes in gene expression, which extend into old age, are key to the life- and
      health-span-extending effects of CR. Further, ST-CR substantially shifted the
      "normo-aging" genomic profile of old control mice toward the "slow-aging" profile
      associated with LT-CR. Therefore, many of the genomic effects of CR are
      established rapidly. Thus, expression profiling should prove useful in quickly
      identifying CR- mimetic drugs and treatments.

PMID- 11535823
TI  - Immunolocalization of UDP-glucose:glycoprotein glucosyltransferase indicates
      involvement of pre-Golgi intermediates in protein quality control.
AB  - The UDP-glucose:glycoprotein glucosyltransferase (GT) is a protein folding sensor
      and glycosyltransferase that constitutes an important component of the protein
      quality control machinery. With the use of quantitative immunogold electron
      microscopy, we established the subcellular distribution of GT in rat liver and
      pancreas and Drosophila melanogaster salivary gland as well as cell lines and
      correlated it with that of glucosidase II, calreticulin, and pre-Golgi
      intermediate markers. Labeling for GT, as well as for glucosidase II and
      calreticulin, was found in the endoplasmic reticulum (ER), including nuclear
      envelope and pre-Golgi intermediates located between ER and Golgi apparatus, and
      in the cell periphery. In the rough ER, labeling for GT was inhomogeneous, with
      variously sized labeled and unlabeled cisternal regions alternating, indicative
      of a meshwork of quality control checkpoints. Notably, labeling intensity for GT
      was highest in pre-Golgi intermediates, corresponding to twice that of rough ER,
      whereas the Golgi apparatus exhibited no specific labeling. These results suggest
      that protein quality control is not restricted to the ER and that the pre-Golgi
      intermediates, by virtue of the presence of GT, glucosidase II, and calreticulin,
      are involved in this fundamental cellular process.

PMID- 11535824
TI  - Structure of the Sec23p/24p and Sec13p/31p complexes of COPII.
AB  - COPII-coated vesicles carry proteins from the endoplasmic reticulum to the Golgi
      complex. This vesicular transport can be reconstituted by using three cytosolic
      components containing five proteins: the small GTPase Sar1p, the Sec23p/24p
      complex, and the Sec13p/Sec31p complex. We have used a combination of
      biochemistry and electron microscopy to investigate the molecular organization
      and structure of Sec23p/24p and Sec13p/31p complexes. The three-dimensional
      reconstruction of Sec23p/24p reveals that it has a bone-shaped structure, (17 nm
      in length), composed of two similar globular domains, one corresponding to Sec23p
      and the other to Sec24p. Sec13p/31p is a heterotetramer composed of two copies of
      Sec13p and two copies of Sec31p. It has an elongated shape, is 28-30 nm in
      length, and contains five consecutive globular domains linked by relatively
      flexible joints. Putting together the architecture of these Sec complexes with
      the interactions between their subunits and the appearance of the coat in COPII
      coated vesicles, we present a model for COPII coat organization.

PMID- 11535825
TI  - Regulation of melastatin, a TRP-related protein, through interaction with a
      cytoplasmic isoform.
AB  - The TRP (transient receptor potential) superfamily includes a group of
      subfamilies of channel-like proteins mediating a multitude of physiological
      signaling processes. The TRP-melastatin (TRPM) subfamily includes the putative
      tumor suppressor melastatin (MLSN) and is a poorly characterized group of TRP
      related proteins. Here, we describe the identification and characterization of an
      additional TRPM protein TRPM4. We reveal that TRPM4 and MLSN each mediate Ca(2+)
      entry when expressed in HEK293 cells. Furthermore, we demonstrate that a short
      form of MLSN (MLSN-S) interacts directly with and suppresses the activity of full
      length MLSN (MLSN-L). This suppression seems to result from the inhibition of
      translocation of MLSN-L to the plasma membrane. We propose that control of
      translocation through interaction between MLSN-S and MLSN-L represents a mode for
      regulating ion channel activity.

PMID- 11535826
TI  - Hematopoietic colony-forming cells derived from human embryonic stem cells.
AB  - Human embryonic stem (ES) cells are undifferentiated, pluripotent cells that can
      be maintained indefinitely in culture. Here we demonstrate that human ES cells
      differentiate to hematopoietic precursor cells when cocultured with the murine
      bone marrow cell line S17 or the yolk sac endothelial cell line C166. This
      hematopoietic differentiation requires fetal bovine serum, but no other exogenous
      cytokines. ES cell-derived hematopoietic precursor cells express the cell surface
      antigen CD34 and the hematopoietic transcription factors TAL-1, LMO-2, and GATA
      2. When cultured on semisolid media with hematopoietic growth factors, these
      hematopoietic precursor cells form characteristic myeloid, erythroid, and
      megakaryocyte colonies. Selection for CD34(+) cells derived from human ES cells
      enriches for hematopoietic colony-forming cells, similar to CD34 selection of
      primary hematopoietic tissue (bone marrow, umbilical cord blood). More terminally
      differentiated hematopoietic cells derived from human ES cells under these
      conditions also express normal surface antigens: glycophorin A on erythroid
      cells, CD15 on myeloid cells, and CD41 on megakaryocytes. The in vitro
      differentiation of human ES cells provides an opportunity to better understand
      human hematopoiesis and could lead to a novel source of cells for transfusion and
      transplantation therapies.

PMID- 11535827
TI  - Dominant/recessive behavior in the expression of molecular information: self
      assembly of inorganic macrocyclic architectures containing coordinatively
      unsaturated ligands.
AB  - The polytopic ligand 1 contains three different metal ion binding subunits
      forming two substructures that code for the self-assembly of two different
      coordination structures (helicate and grid type) under metal ion complexation.
      Reaction with Cu(II) and Zn(II) ions generates the coordinatively unsaturated
      architectures 8 and 9 resulting from the formation of two double helicate
      arrangements. Their crystal structure has been determined by x-ray diffraction.
      These results show that the double helical motif is expressed at the expense of
      the grid type one, indicating the dominant/recessive behavior of the system.
      Together with earlier studies on the linear combination and crossover processing
      schemes, the dominant/recessive generation of 8 and 9 completes the demonstration
      of principle of the modes of multiple expression of molecular information in a
      multicode programmed chemical system.

PMID- 11535828
TI  - Biosynthesis and insecticidal properties of plant cyclotides: the cyclic knotted
      proteins from Oldenlandia affinis.
AB  - Several members of the Rubiaceae and Violaceae families produce a series of
      cyclotides or macrocyclic peptides of 29-31 amino acids with an embedded cystine
      knot. We aim to understand the mechanism of synthesis of cyclic peptides in
      plants and have isolated a cDNA clone that encodes the cyclotide kalata B1 as
      well as three other clones for related cyclotides from the African plant
      Oldenlandia affinis. The cDNA clones encode prepropeptides with a 20-aa signal
      sequence, an N-terminal prosequence of 46-68 amino acids and one, two, or three
      cyclotide domains separated by regions of about 25 aa. The corresponding
      cyclotides have been isolated from plant material, indicating that the cyclotide
      domains are excised and cyclized from all four predicted precursor proteins. The
      exact processing site is likely to lie on the N-terminal side of the strongly
      conserved GlyLeuPro or SerLeuPro sequence that flanks both sides of the cyclotide
      domain. Cyclotides have previously been assigned an antimicrobial function; here
      we describe a potent inhibitory effect on the growth and development of larvae
      from the Lepidopteran species Helicoverpa punctigera.

PMID- 11535829
TI  - A src family tyrosine kinase inhibits neurotransmitter release from neuronal
      cells.
AB  - Tyrosine kinases are expressed in many tissues, particularly in the central
      nervous system, and regulate various cellular functions. We report here that a
      src family tyrosine kinase-specific inhibitor, PP2, enhances neurotransmitter
      release from PC12 cells and primary cultured neurons. PP2 enhances only Ca(2+)
      dependent release; it does not affect basal release. These effects result from an
      enhancement of vesicular exocytosis and not from the reuptake or refilling of
      neurotransmitters because Ca(2+)-dependent secretion of an exogenously expressed
      reporter protein, the human growth hormone (hGH), is also enhanced by PP2.
      Overexpression of constitutive active v-src, but not of a kinase-inactive mutant,
      suppressed Ca(2+)-dependent release. In PP2-treated cells, Pyk2, paxillin, and
      some other proteins showed a decrease in tyrosine phosphorylation, and the
      enhancement of tyrosine phosphorylation of these proteins in response to Ca(2+)
      influx was also reduced. Electron and fluorescence microscopy showed that PP2
      treatment induced morphological change and decreased phalloidin reactivity at the
      filopodium-like structures on the processes of PC12 cells. Interestingly,
      inhibition of actin polymerization with cytochalasin D and latrunculin A enhanced
      Ca(2+)-dependent, but not basal, release. It is possible that a src family
      tyrosine kinase, through the regulation of actin dynamics, has an inhibitory
      function to regulate neurotransmitter release.

PMID- 11535830
TI  - Functionalized xenon as a biosensor.
AB  - The detection of biological molecules and their interactions is a significant
      component of modern biomedical research. In current biosensor technologies,
      simultaneous detection is limited to a small number of analytes by the spectral
      overlap of their signals. We have developed an NMR-based xenon biosensor that
      capitalizes on the enhanced signal-to-noise, spectral simplicity, and chemical
      shift sensitivity of laser-polarized xenon to detect specific biomolecules at the
      level of tens of nanomoles. We present results using xenon "functionalized" by a
      biotin-modified supramolecular cage to detect biotin-avidin binding. This
      biosensor methodology can be extended to a multiplexing assay for multiple
      analytes.

PMID- 11535831
TI  - Inhibition of transcription factor-DNA complexes and gene expression by a
      microgonotropen.
AB  - Developing minor groove-binding drugs to selectively inhibit transcription factor
      (TF)/DNA interactions and accompanying gene expression is a current goal in drug
      development studies. Equipping minor groove-binding agents with positively
      charged, major groove-contacting side chains yields microgonotropens (MGTs).
      Previously, we demonstrated that MGTs were superior inhibitors of TF/DNA
      complexes in cell-free assays compared with "classical" groove binders, but MGTs
      showed limited ability to inhibit gene expression. To determine what chemical
      characteristics contribute to or improve activity, we evaluate five MGTs for
      their effectiveness in inhibiting TF complex formation and resultant
      transcription by using the c-fos serum response element (SRE) as a target. MGT L1
      binds DNA via a bisbenzimidazole equipped with a tripyrrole moiety. It is
      compared with analog L2, which has been functionalized with propylamines on each
      of the three pyrroles. L2, which binds DNA at subpicomolar concentrations, was at
      least three orders of magnitude more potent than L1 at inhibiting TF binding to
      the c-fos SRE in cell-free assays. Unlike L1 and previous MGTs, L2 also inhibited
      endogenous c-fos expression in NIH 3T3 cells at micromolar levels.
      Structure/activity relationships suggest that, although the tripyrrole/polyamine
      functional group of L2 may be largely responsible for its inhibition of TF
      complexes in cell-free assays, its bisbenzimidazole moiety appears to impart
      improved cellular uptake and activity. These findings make L2 a promising lead
      candidate for future, rational MGT design.

PMID- 11535832
TI  - Cloning and characterization of a histone deacetylase, HDAC9.
AB  - Histone deacetylase (HDAC) catalyzes the removal of the acetyl group from the
      lysine residues in the N-terminal tails of nucleosomal core histones. Eight human
      HDACs have been identified so far. Here, we report the identification of a ninth
      member of the HDAC family, designated HDAC9. HDAC9 is a class II HDAC and its
      gene resides on human chromosome 7. HDAC9 has several alternatively spliced
      isoforms. One of these isoforms is histone deacetylase-related protein or myocyte
      enhancer-binding factor 2-interacting transcriptional repressor that we and
      others have previously reported and which does not possess an HDAC catalytic
      domain. The longest of the HDAC9 isoforms contains 1,011 aa. The isoform,
      designated HDAC9a, is 132 aa shorter at the C terminus than HDAC9. Also, we have
      identified isoforms of HDAC9 that lack the nuclear localization signal. Similar
      to histone deacetylase-related protein, HDAC9 transcripts are expressed at high
      levels in brain and skeletal muscle. The ratio of HDAC9 and HDAC9a transcripts
      differs among the tissues examined. HDAC9 and HDAC9a contain the HDAC catalytic
      domain, and Flag-tagged HDAC9 and HDAC9a possess deacetylase activity. HDAC9 and
      HDAC9a also repress myocyte enhancer-binding factor 2-mediated transcription. In
      the present study, we have identified HDAC9 and a number of alternatively spliced
      isoforms of HDAC9 with potentially different biological activities.

PMID- 11535833
TI  - Overlapping recognition determinants within the ssrA degradation tag allow
      modulation of proteolysis.
AB  - The ssrA tag, an 11-aa peptide added to the C terminus of proteins stalled during
      translation, targets proteins for degradation by ClpXP and ClpAP. Mutational
      analysis of the ssrA tag reveals independent, but overlapping determinants for
      its interactions with ClpX, ClpA, and SspB, a specificity-enhancing factor for
      ClpX. ClpX interacts with residues 9-11 at the C terminus of the tag, whereas
      ClpA recognizes positions 8-10 in addition to residues 1-2 at the N terminus.
      SspB interacts with residues 1-4 and 7, N-terminal to the ClpX-binding
      determinants, but overlapping the ClpA determinants. As a result, SspB and ClpX
      work together to recognize ssrA-tagged substrates efficiently, whereas SspB
      inhibits recognition of these substrates by ClpA. Thus, dissection of the
      recognition signals within the ssrA tag provides insight into how multiple
      proteins function in concert to modulate proteolysis.

PMID- 11535834
TI  - A simple model host for identifying Gram-positive virulence factors.
AB  - We demonstrate the use of the nematode Caenorhabditis elegans as a facile and
      inexpensive model host for several Gram-positive human bacterial pathogens.
      Enterococcus faecalis, Streptococcus pneumoniae, and Staphylococcus aureus, but
      not Bacillus subtilis, Enterococcus faecium, or Streptococcus pyogenes, kill
      adult C. elegans. Focusing our studies on the enterococcal species, we found that
      both E. faecalis and E. faecium kill C. elegans eggs and hatchlings, although
      only E. faecalis kills the adults. In the case of adults, a low inoculum of E.
      faecalis grows to a high titer in the C. elegans intestine, resulting in a
      persistent infection that cannot be eradicated by prolonged feeding on E.
      faecium. Interestingly, a high titer of E. faecium also accumulates in the
      nematode gut, but does not affect the longevity of the worms. Two E. faecalis
      virulence-related factors that play an important role in mammalian models of
      infection, fsr, a putative quorum-sensing system, and cytolysin, are also
      important for nematode killing. We exploit the apparent parallels between Gram
      positive infection in simple and more complex organisms by using the nematode to
      identify an E. faecalis virulence factor, ScrB, which is relevant to mammalian
      pathogenesis.

PMID- 11535835
TI  - Hydration of the peptide backbone largely defines the thermodynamic propensity
      scale of residues at the C' position of the C-capping box of alpha-helices.
AB  - The C' position of the C-capping box is the second residue outside of the helix.
      Statistical analysis of residue distribution at the C' position in the alpha
      helices' C-capping box showed that different amino acid residues occur with
      different probabilities, with the strongest preference being for glycine. To
      understand the physico-chemical basis for this preference, we studied the effects
      that 17 amino acid substitutions at the C' position in an alpha-helix of
      ubiquitin have on the stability of this protein. We determined the following rank
      order of amino acid residues at the C' position with respect to their effect on
      the stability:
      Gly>His>Asn>Arg>Lys>Gln>Ala>Phe>Met>Ser>Asp>Glu>Trp>Thr>Pro>Ile>Val. The effect
      of the amino acid substitutions on the structure also was evaluated by comparing
      the (1)H-(15)N heteronuclear sequential quantum correlation spectra and showed no
      significant changes in the structures of the most stable (Gly) and the least
      stable (Val) variants. The obtained changes in stability highly correlate (r =
      0.85) with the statistical distribution of the residues at the C' position
      indicating that the measured thermodynamic propensities are unbiased by secondary
      interactions. We also found that the measured thermodynamic propensities
      correlate well with the amide hydrogen exchange data on short model peptides (r =
      0.85) and the calculated hydration of the peptide backbone (r = 0.88). These
      results combined with the changes in enthalpy and entropy of unfolding of
      ubiquitin variants suggest that dehydration of the peptide backbone plays a
      significant role in defining the thermodynamic propensity scale at the C'
      position of the C-capping box in alpha-helices. This propensity scale is useful
      for protein secondary structure predictions and protein design.

PMID- 11535836
TI  - Plant gene expression response to Agrobacterium tumefaciens.
AB  - To elucidate the nature of plant response to infection and transformation by
      Agrobacterium tumefaciens, we compared the cDNA-amplified fragment length
      polymorphism (AFLP) pattern of Agrobacterium- and mock-inoculated Ageratum
      conyzoides plant cell cultures. From 16,000 cDNA fragments analyzed, 251 (1.6%)
      were differentially regulated (0.5% down-regulated) 48 h after cocultivation with
      Agrobacterium. From 75 strongly regulated fragments, 56 were already regulated 24
      h after cocultivation. Sequence similarities were obtained for 20 of these
      fragments, and reverse transcription-PCR analysis was carried out with seven to
      confirm their cDNA-AFLP differential pattern. Their sequence similarities suggest
      a role for these genes in signal perception, transduction, and plant defense.
      Reverse transcription-PCR analysis indicated that four genes involved in defense
      response are regulated in a similar manner by nonpathogenic bacteria, whereas one
      gene putatively involved in signal transduction appeared to respond more strongly
      to Agrobacterium. A nodulin-like gene was regulated only by Agrobacterium. These
      results demonstrate a rapid plant cell response to Agrobacterium infection, which
      overlaps a general response to bacteria but also has Agrobacterium-specific
      features.

PMID- 11535837
TI  - Stone tool function at the paleolithic sites of Starosele and Buran Kaya III,
      Crimea: behavioral implications.
AB  - Stone tools are often the most abundant type of cultural remains at Paleolithic
      sites, yet their function is often poorly understood. Investigations of stone
      tool function, including microscopic use-wear and residue analyses, were
      performed on a sample of artifacts from the Paleolithic sites of Starosele
      (40,000-80,000 years BP) and Buran Kaya III (32,000-37,000 years BP). The Middle
      Paleolithic levels at Starosele exhibit a typical variant of the local Micoquian
      Industry. The artifacts from Buran Kaya III most closely resemble an Early
      Streletskayan Industry associated with the early Upper Paleolithic. The results
      of the functional analyses suggest that hominids at both sites were exploiting
      woody and starchy plant material as well as birds and mammals. Both sites show
      evidence of hafting of a wide variety of tools and the possible use of projectile
      or thrusting spears. These analyses were performed by using two different
      techniques conducted by independent researchers. Combined residue and use-wear
      analyses suggest that both the Upper Paleolithic and Middle Paleolithic hominids
      at these sites were broad-based foragers capable of exploiting a wide range of
      resources.

PMID- 11535838
TI  - Single-cell analysis of signal transduction in CD4 T cells stimulated by antigen
      in vivo.
AB  - Flow cytometry was used to study signaling events in individual CD4 T cells after
      antigen recognition in the body. Phosphorylation of c-jun and p38 mitogen
      activated protein kinase was detected within minutes in all antigen-specific CD4
      T cells in secondary lymphoid tissues after injection of peptide antigen into the
      bloodstream. The remarkable rapidity of this response correlated with the finding
      that most naive T cells are in constant contact with dendritic antigen-presenting
      cells. Contrary to predictions from in vitro experiments, antigen-induced c-jun
      and p38 mitogen-activated protein kinase phosphorylation did not depend on CD28
      signals and was insensitive to inhibition by cyclosporin A. Our results highlight
      the efficiency of the in vivo immune response and underscore the need to verify
      which signaling pathways identified in vitro actually operate under physiological
      conditions.

PMID- 11535840
TI  - Randomized, prospective, double-blind, placebo-controlled trial of effect of
      nitroglycerin ointment on pain after hemorrhoidectomy.
AB  - PURPOSE: Fissure-in-ano is characterized by pain, bleeding, and internal anal
      sphincter hypertonicity. Spasm of the internal sphincter also plays a role in
      hemorrhoidal disease and may be a source of anal pain after hemorrhoid surgery.
      Inducing sphincter relaxation with a nitroglycerin ointment has shown promise in
      healing anal fissures and relieving symptoms of pain. Our study attempts to test
      the hypothesis that topical nitroglycerin applied to the perianal region is
      beneficial in reducing pain after hemorrhoidectomy. METHODS: After
      hemorrhoidectomy 39 patients were randomly assigned to receive 0.2 percent
      nitroglycerin ointment (n = 19) or placebo (n = 20). Ointments were applied to
      the perianal region three times daily for seven days. Patients were prescribed
      hydrocodone bitartrate to take as needed. Visual analog scales were used to
      measure postoperative pain intensity and ointment benefits. Patients completed
      questionnaires to record medication morbidity and number of prescribed or
      nonprescribed medications taken. RESULTS: Patients using nitroglycerin had less
      pain and greater benefit from ointment than those did in the placebo group, but
      differences were not significant. Narcotic use was higher in the placebo group
      when considered on a daily basis, but was statistically significant on the second
      postoperative day only (P < 0.05). Morbidity from ointment application was
      significantly higher in the nitroglycerin group (P < 0.002) and included a
      headache in 8 of 19 patients. Nonsteroidal anti-inflammatory drugs and
      acetaminophen were not prescribed, but were taken more frequently in
      nitroglycerin patients (P < 0.0003). CONCLUSION: Perianal application of 0.2
      percent nitroglycerin ointment after hemorrhoidectomy significantly reduced
      narcotic requirements on the second postoperative day. Headaches and a subsequent
      need for nonnarcotic medications may limit benefits of nitroglycerin.

PMID- 11535839
TI  - Immune mimicry in malaria: Plasmodium falciparum secretes a functional histamine
      releasing factor homolog in vitro and in vivo.
AB  - The Plasmodium falciparum translationally controlled tumor protein (TCTP) is a
      homolog of the mammalian histamine-releasing factor (HRF), which causes histamine
      release from human basophils and IL-8 secretion from eosinophils. Histamine, IL
      8, and eosinophils have been reported to be elevated in patients with malaria.
      This study was undertaken to determine whether malarial TCTP is found in the
      plasma of malaria-infected patients and to determine whether it has HRF biologic
      activity. Malarial TCTP was found in lightly infected human volunteers and in
      heavily infected Malawian children, but not in uninfected patients. Recombinant
      malarial TCTP, like HRF, stimulated histamine release from basophils and IL-8
      secretion from eosinophils in vitro. Whereas malarial TCTP was less active than
      HRF, the concentrations that were effective in vitro could be achievable in vivo.
      These data suggest that malarial TCTP, present in human plasma during a malarial
      illness, may affect host immune responses in vivo.

PMID- 11535842
TI  - A randomized trial of oral vs. topical diltiazem for chronic anal fissures.
AB  - INTRODUCTION: Chemical sphincterotomy has proved effective in treating chronic
      anal fissure. Glyceryl trinitrate is the most widely used agent, and topical 0.2
      percent glyceryl trinitrate ointment heals up to two thirds of chronic anal
      fissures. Unfortunately, however, many patients experience troublesome headaches
      as a side effect of this treatment. This study assessed the effectiveness of oral
      and topical diltiazem in healing chronic fissures. METHODS: Fifty consecutive
      patients with chronic anal fissures were randomly assigned to receive oral (60
      mg) or topical (2 percent gel) diltiazem twice daily for up to eight weeks. Anal
      manometry was performed before and after the first dose, and blood pressure was
      recorded at 15-minute intervals. Patients were reviewed fortnightly, pain was
      expressed with a visual linear analog scale, blood pressure was recorded, fissure
      healing was assessed, and side effects were noted. RESULTS: Twenty-four patients
      received oral diltiazem, and 26 received topical diltiazem. Mean (+/- standard
      error of the mean) maximum resting anal pressures fell by 15 and 23 percent from
      95 +/- 4 to 81 +/- 4 and from 102 +/- 5 to 79 +/- 5 cm H2O in the two groups,
      respectively. There was no significant reduction in blood pressure during the
      study or at follow-up in either group. Fissure healing was complete in 9 patients
      (38 percent) receiving oral diltiazem and 15 (65 percent) on topical treatment by
      eight weeks. Oral diltiazem caused side effects in eight patients (rash, two;
      headaches, two; nausea or vomiting, three; reduced smell and taste, one), whereas
      no side effects were seen in those receiving topical therapy (P = 0.001).
      CONCLUSION: Oral and topical diltiazem heal chronic anal fissures. Topical
      diltiazem is more effective, achieving healing rates comparable to those reported
      with topical nitrates, with significantly fewer side effects.

PMID- 11535843
TI  - Rubber band ligation for hemorrhoidal disease can be safely performed in select
      HIV-positive patients.
AB  - PURPOSE: Many surgeons have abandoned the use of rubber band ligation for the
      treatment of hemorrhoids in patients infected with human immunodeficiency virus
      because of the belief that this procedure could lead to disastrous outcomes. This
      study was designed to evaluate the safety and efficacy of rubber band ligation in
      otherwise healthy human immunodeficiency virus-positive patients. METHODS: A
      retrospective chart review of healthy human immunodeficiency virus-positive
      patients who underwent rubber band ligation for symptomatic hemorrhoids between
      April 1993 and May 2000 was conducted. RESULTS: The study group comprised 11
      patients. All patients were male, with a median age of 48 (range, 32-64) years.
      Mean T-cell helper count was 450 (range, 200-1,000) cells/microl. A median of 2
      (range, 1-4) rubber band ligations were performed per patient. The median length
      of follow-up was seven (range, 1-28) months. There were no deaths or
      complications in any study group patient. Eight patients (73 percent) had
      excellent results, with complete resolution of symptoms. Two patients (18
      percent) had initial improvement but subsequently had hemorrhoidectomy because of
      recurrent symptoms. Only one patient (9 percent) had no benefit from rubber band
      ligation and underwent hemorrhoidectomy. CONCLUSION: These data suggest that
      asymptomatic human immunodeficiency virus-positive patients can be treated safely
      and effectively with rubber band ligation for symptomatic hemorrhoids.

PMID- 11535845
TI  - The effect of intraoperative thoracic epidural anesthesia and postoperative
      analgesia on bowel function after colorectal surgery: a prospective, randomized
      trial.
AB  - PURPOSE: Colorectal surgery is associated with postoperative ileus, which
      contributes to delayed discharge. This study was designed to investigate the
      effect of thoracic epidural anesthesia and analgesia on gastrointestinal function
      after colorectal surgery under standardized controlled postoperative care.
      METHODS: Forty-two patients diagnosed with either colonic cancer, diverticulitis,
      polyps, or adenoma, and scheduled for elective colorectal surgery, were randomly
      assigned to either postoperative patient-controlled analgesia (PCA) with
      intravenous morphine (n = 21) or epidural analgesia with a mixture of bupivacaine
      and fentanyl (n = 21). Postoperative early oral feeding and assistance to
      mobilization were offered to all patients. Pain visual analog scale (1-100 mm),
      passage of flatus and bowel movements, length of hospital stay, and readiness for
      discharge were recorded. RESULTS: Pain visual analog scale (visual analog scale,
      1-100 mm) at rest, on coughing, and daily on mobilization was significantly lower
      in the epidural group compared with the patient-controlled analgesia group.
      Median values for the visual analog scale group were 7 (95 percent confidence
      interval, 2-18) mm, 19 (95 percent confidence interval, 4-38) mm, and 10 (95
      percent confidence interval, 5-33) mm, respectively, and, for the patient
      controlled analgesia group, were 24 (95 percent confidence interval, 18-51) mm,
      59 (95 percent confidence interval, 33-74) mm, and 40 (95 percent confidence
      interval, 29-79) mm, respectively (P < 0.01). Intake of protein and calories and
      time out of bed were similar in both groups. Mean time intervals +/- standard
      deviation from surgery to first flatus and first bowel movement occurred earlier
      in the epidural group, 1.9 +/- 0.6 days and 3.1 +/- 1.7 days, respectively,
      compared with patient-controlled analgesia, 3.6 +/- 1.5 days and 4.6 +/- 1.6
      days, respectively (P < 0.01). Postoperative complications occurred in 33 percent
      of the patient-controlled analgesia group and 28 percent of the epidural group.
      There was no significant difference in length of hospital stay between the two
      groups with a mean of 7.3 +/- 3.7 days in the patient-controlled analgesia group
      and 8.5 +/- 4.2 days in the epidural group. Readiness for discharge was similar
      in both groups. CONCLUSION: Thoracic epidural analgesia has distinct advantages
      over patient-controlled analgesia morphine in providing superior quality of
      analgesia and shortening the duration of postoperative ileus. However, discharge
      home was not faster, indicating that other perioperative factors influence the
      length of hospital stay.

PMID- 11535848
TI  - Impact of a surgeon-trained observer on accuracy of colorectal surgical site
      infection rates.
AB  - PURPOSE: The aims of this study were 1) to establish accurate and reproducible
      baseline surgical site infection rates for our department and 2) to identify risk
      factors associated with surgical site infection in patients undergoing surgery on
      a colorectal service. METHODS: Phase I--Surgical site infection grading between
      the surgeon-trainer and the observer-trainee was validated using a four-point
      scale for wound evaluation previously used by our institution. Phase II--Patients
      undergoing colorectal surgery were prospectively monitored. The observed surgical
      site infection rate was compared with morbidity and mortality reports. Patient
      and perioperative variables were analyzed for their effect on surgical site
      infection using the chi-squared test. Risk factors approaching significance on
      univariate analysis (P < 0.2) were entered into a multivariate stepwise logistic
      regression model. RESULTS: Concordance on surgical site infection grading between
      the surgeon-trainer and the observer-trainee improved from an initial 79 percent
      to 96 percent during the validation period. The surgeon-trained observer reported
      a surgical site infection rate of 7.2 percent vs. a morbidity and mortality
      reported rate of 3.3 percent. Among the variables examined, obesity and surgical
      procedure category were significantly associated with surgical site infection
      rates. The effect of prophylactic antibiotics and prior chemotherapy, radiation,
      or steroid therapy on surgical site infection rates approached significance. A
      logistic regression analysis incorporating these risk factors for surgical site
      infection accurately predicted infection status 93 percent of the time.
      CONCLUSION: Use of a surgeon-trained observer doubles the detection rate of
      postoperative surgical site infection. Accurate, prospective assessment
      identifies risk factors significantly associated with increased surgical site
      infection rates in colorectal surgical patients.

PMID- 11535846
TI  - Relationship between APC genotype, polyp distribution, and oral sulindac
      treatment in the colon and rectum of patients with familial adenomatous
      polyposis.
AB  - PURPOSE: Familial adenomatous polyposis is an inherited colorectal cancer
      syndrome characterized by the presence of multiple adenomatous colorectal polyps.
      Molecular studies have revealed that germline mutations in the APC gene are the
      underlying cause of the disease. The nonsteroidal anti-inflammatory agent
      sulindac has been shown to reduce the number of colorectal adenomas. Most
      sulindac trials in the large bowel have focused on the distal colon and
      relatively little is known about its effect on the proximal colon. Moreover, it
      is unknown whether the site of the APC mutation affects the efficacy of sulindac.
      METHODS: This study investigated whether there were regional differences in the
      effect of sulindac on the colon and whether response to sulindac was dependent on
      the site of mutation in the APC gene. In an open prospective study 17 patients
      with familial adenomatous polyposis were treated with 300 mg oral sulindac daily
      for four months followed by a washout phase of six months. Ten of the patients
      had an intact colon and seven had rectal stumps only. The number, size, and the
      degree of dysplasia of the adenomas were evaluated by colonoscopy at entry, end
      of treatment and end of the study. RESULTS: Overall, a statistically significant
      decrease in the number of adenomas was observed (120 +/- 112 to 28 +/- 64, P =
      0.007). After cessation of sulindac treatment the number of adenomas increased to
      48 +/- 44.5, but remained significantly lower than the values observed at
      baseline. In the ten patients with intact colons, adenomas decreased by sevenfold
      in the proximal colon (103 +/- 73 to 15.1 +/- 47.4, P = 0.011) and twofold in the
      distal colon (80 +/- 52 to 29.6 +/- 37.2, P = 0.005). The size of adenomas and
      the grade of dysplasia also decreased. No correlation could be seen between the
      APC mutation site and the response to treatment. CONCLUSION: These data indicate
      that sulindac reduces the number of adenomas in the entire colon and that the
      effect seems to be more pronounced in the proximal colon.

PMID- 11535849
TI  - Single alteration of p53 or E-cadherin genes can alter the surgical resection
      benefit in an experimental model of colon cancer.
AB  - PURPOSE: p53 and E-cadherin mutations are associated with a high risk of
      metastatic potential and local recurrence after colorectal surgery. LoVo, a human
      colon cancer cell line expressing a wild-type p53 and a normal E-cadherin, was
      studied. Clone LoVo-XC17 was obtained from LoVo cells transfected with a vector
      bearing a p53 273his mutation. Clone LoVo-92R4 was obtained from LoVo by culture
      cells with an E-cadherin down-regulation. LoVo, LoVo-XC17, and LoVo-92R4 were
      studied for in vivo behavior in a surgical intracolonic graft model. METHODS: Ten
      nude mice were used per cell line. A colonic tumor was obtained by tumor
      implantation into the cecal wall. The cecal tumor was resected at Day 15; at this
      time the volumes of the different tumors were similar. RESULTS: Surgical
      resection of the LoVo tumor led to 100 percent disease-free animals at one month.
      Surgical resection of mice grafted with the LoVo-XC17 line did not cure any mice
      (0/10; P = 0.001). Mice had local recurrences (10/10), mesenteric lymph node
      metastases (9/10), liver metastases (2/10), and peritoneal carcinomatosis (8/10).
      Surgical resection of LoVo-92R4 tumors led to cures in 30 percent (3/10), whereas
      70 percent had isolated mesenteric lymph node metastases (7/10; P = 0.003).
      CONCLUSION: In this model surgical tumor resection was consistently effective for
      colonic tumors with functional p53 and E-cadherin, it was consistently
      ineffective with tumors displaying a mutated p53, and it was partially effective
      with E-cadherin-deficient tumors. This study shows that the alteration of a
      single gene can be associated with a profound alteration of surgical resection
      benefit.

PMID- 11535851
TI  - Preoperative chemoradiotherapy and radical surgery for locally advanced distal
      rectal adenocarcinoma: pathologic findings and clinical implications.
AB  - PURPOSE: Preoperative chemoradiotherapy followed by radical surgical resection
      has been the preferred treatment for patients presenting with locally advanced
      distal rectal carcinoma at our institutions. We postulated that chemoradiotherapy
      induced pathologic response of the primary tumor would identify which patients
      would be candidates for local excision as definitive surgical therapy. METHODS: A
      retrospective analysis of 60 patients with palpable, locally advanced, distal
      rectal adenocarcinomas treated from 1995 to 2000 was performed. All patients
      received preoperative chemoradiotherapy consisting of 5-fluorouracil (325
      mg/m(2)) and leucovorin (20 mg/m(2)) by bolus infusion on Days 1 through 5 and 29
      through 33 delivered concurrently with at least 45.0 to 50.4 Gy of pelvic
      radiation, followed six to eight weeks later by radical surgery and then adjuvant
      chemotherapy. RESULTS: Among 60 patients (20 females) there was a mean age of
      58.7 (28-84) years. Clinical staging was as follows: Stage II, 14 patients (23
      percent); Stage III, 35 patients (58 percent); and Stage IV, 11 patients (18
      percent). Pathologic examination revealed that negative margins were obtained in
      58 patients (97 percent). Downstaging to T0-2N0 was achieved in 17 patients (28
      percent), with five (8 percent) achieving a pathologically complete response.
      Lymph nodes were positive in 24 patients (40 percent) despite chemoradiotherapy.
      Pathologic node positivity was found in 0 of 5 pT0 patients, 9 (41 percent) of 22
      pT1 or pT2, and 15 (45 percent) of 33 pT3. Clinical stage, tumor size, pathologic
      stage, and adverse histologic features could not reliably predict pN0 status,
      except pT0 (5 patients only). CONCLUSIONS: Preoperative chemoradiotherapy often
      downsizes and downstages locally advanced rectal carcinoma. Neither pretreatment
      clinical characteristics, response to preoperative chemoradiotherapy, or
      pathologic features reliably predict pN0 status. Therefore, local excision is not
      recommended as an alternative to radical surgery for locally advanced
      adenocarcinoma of the distal rectum regardless of the response of the primary
      tumor to preoperative chemoradiotherapy.

PMID- 11535850
TI  - Phase II clinical trial of preoperative combined chemoradiation for T3 and T4
      resectable rectal cancer: preliminary results.
AB  - PURPOSE: Although preoperative chemoradiation for high-risk rectal cancer may
      improve survival and local recurrence rate, its adverse effects are not well
      defined. This prospective study evaluated the use of preoperative chemoradiation
      for T3 and T4 resectable rectal cancer, with special emphasis on treatment
      morbidity, pathologic remission rate, quality of life, and anorectal function.
      METHODS: Forty-two patients (30 men, 12 women) were enrolled in the study. Median
      distance of the distal tumor margin from the anal verge was 6.5 cm. Preoperative
      staging was based on digital rectal examination, endorectal ultrasound, and
      computed tomography. None of the patients had distant metastases. All patients
      had 45 Gy (1.8 Gy/day in 25 fractions) over five weeks, plus 5-fluorouracil (350
      mg/m(2)/day) and leucovorin (20 mg/m(2)/day) bolus on days 1 to 5 and 29 to 33.
      Quality of life was assessed with the European Organization for Research and
      Treatment of Cancer 30-item quality-of-life questionnaire (QLQ-C30) and its
      colorectal cancer-specific module (QLQ-CR38) questionnaires. Objective anorectal
      function was assessed by anorectal manometry and pudendal nerve terminal motor
      latency. Surgery was performed 46 (range, 24-63) days after completion of
      adjuvant therapy. RESULTS: Nineteen patients (45 percent) had Grade 3 or 4
      chemoradiation-induced toxic reactions. Four patients developed intercurrent
      distant metastases or intraperitoneal carcinomatosis at completion of
      chemoradiation. Thirty-eight patients underwent surgical resection:
      abdominoperineal resection, anterior resection, and Hartmann's procedure were
      performed in 55 percent, 39 percent (11 of 15 patients had a diverting stoma),
      and 5 percent, respectively. Major surgical complications occurred in 7 patients
      (18 percent) and included anastomotic leak (n = 1), pelvic abscess (n = 1), small
      bowel obstruction (n = 3), and wound breakdown (n = 2). Final pathology was Stage
      0 (no residual disease), I, II, and III in 6 (16 percent), 7 (18 percent), 9 (24
      percent), and 16 (42 percent) patients, respectively. There was a deterioration,
      after chemoradiation and surgery, in the quality of life on all subscales
      assessed, with physical, role, and social function being most severely affected.
      The symptoms most adversely affected were micturition, defecation, and
      gastrointestinal problems. Body image and sexual enjoyment deteriorated in both
      men and women. Chemoradiation alone led to prolonged pudendal nerve terminal
      motor latency in 57 percent of 7 patients assessed. CONCLUSION: Preliminary
      results have identified defined costs with preoperative chemoradiation, which
      included treatment-induced toxicity, a high stoma rate, and adverse effects on
      quality of life and anorectal function.

PMID- 11535852
TI  - Angiogenesis at the site of deepest penetration predicts lymph node metastasis of
      submucosal colorectal cancer.
AB  - PURPOSE: Intratumor microvessel count has been reported as a useful prognostic
      factor in patients with cancer of various organs. This study was undertaken to
      clarify the relation between microvessel count and lymph node metastasis in
      submucosal colorectal cancer. METHODS: Microvessel count was estimated in 254
      invasive tumors that had been resected from patients with submucosal colorectal
      cancer. Immunohistochemistry with antibodies against CD34 was performed on
      archival specimens, and microvessel counts were estimated based on the average
      count of three fields (original magnification, x400) in the most vascular area at
      the site of deepest submucosal penetration. RESULTS: Microvessel count ranged
      from 10 to 98, with a median of 40. Lesions with high microvessel counts (> or
      =40) had a significantly higher incidence of lymph node metastasis than those
      with low microvessel counts (<40; 21.8 percent vs. 6.2 percent). None of the 79
      lesions with low microvessel counts and submucosal invasion up to a depth of
      1,500 microm had metastasized to the lymph nodes. In multivariate analysis,
      microvessel count was an independent risk factor for lymph node metastasis in
      submucosal colorectal cancer (P = 0.0026). CONCLUSION: Microvessel count at the
      site of deepest submucosal penetration can be one of the most useful predictors
      for lymph node metastasis. Analysis that combines microvessel count and depth of
      submucosal invasion may predict the occurrence of lesions without lymph node
      metastasis.

PMID- 11535853
TI  - How does pouch construction for a final diagnosis of Crohn's disease compare with
      ileoproctostomy for established Crohn's proctocolitis?
AB  - PURPOSE: There is a difference of opinion concerning the role of ileal pouch-anal
      anastomosis in Crohn's disease, even in the absence of small-bowel or perianal
      disease. One view is that ileal pouch-anal anastomosis should never be
      entertained, the other is that ileal pouch-anal anastomosis, like
      ileoproctostomy, can be justified sometimes, because it allows young people a
      period of stoma-free life. The aim of this study was to examine the outcome of
      ileal pouch-anal anastomosis and to contrast it with ileoproctostomy in patients
      with Crohn's disease without small-bowel or perianal disease. METHODS: Ileal
      pouch-anal anastomosis was performed in 23 patients with Crohn's disease (12 of
      whom had evidence of Crohn's disease at the time of operation and 11 who were
      eventually found to have Crohn's disease as a result of complications) and
      ileoproctostomy in 35. Patients were matched for age, gender, follow-up, and
      medication, but all ileoproctostomy cases had relative rectal sparing. Thus, the
      groups were not comparable and the reasons for ileal pouch-anal anastomosis and
      ileoproctostomy were therefore quite different. RESULTS: The outcome in ileal
      pouch-anal anastomosis at a mean follow-up of 10.2 years was pouch excision, 11
      (47.8 percent); proximal stoma, 1 (4.3 percent; patient preference); average
      small-bowel resection, 65 cm; persistent perineal sinus, 8 of 11 having pouch
      excision (73 percent); and mean time in hospital, 37 (range, 8-108) days. Of
      those in circuit having ileal pouch-anal anastomosis (n = 12), 24-hour bowel
      frequency was 6, with no incontinence or urgency, but 6 (50 percent) were on
      medication. When ileal pouch-anal anastomosis was done for Crohn's disease in the
      resection specimen, only 4 of 12 (33 percent) were excised compared with 7 of 11
      (64 percent) in whom the diagnosis was made as a result of complications. The
      outcome in ileoproctostomy at a mean follow-up of 10.9 years was rectal excision
      in 3 (8 percent), proximal stoma in 1 (3 percent), average small-bowel resection
      was 15 cm, persistent perineal sinus in 1 (3 percent), and time in hospital was
      21 (range, 8-36) days. Of those in circuit (n = 32), 24-hour bowel frequency was
      5, 2 had incontinence, 3 had urgency, and 12 (36 percent) were taking medication.
      CONCLUSIONS: These results indicate that the overall outcome of ileal pouch-anal
      anastomosis is inferior to that of ileoproctostomy, especially if Crohn's disease
      was diagnosed as a result of complications. Nevertheless, the functional results
      of those with a successful outcome are comparable.

PMID- 11535854
TI  - A lifetime of learning.

PMID- 11535855
TI  - Computed tomographic features of colorectal carcinoma liver metastases predict
      posthepatectomy patient survival.
AB  - PURPOSE: The gross appearance of colorectal carcinoma liver metastases reflects
      the biologic behavior of the tumor, yielding prognostic information. The aims of
      this retrospective study were to determine whether preoperative computed
      tomographic features of colorectal carcinoma liver metastases reflect the gross
      appearance of resected specimens and whether these computed tomographic hepatic
      features predict survival after hepatectomy. METHODS: Eighty-five patients
      underwent curative partial hepatectomy for colorectal carcinoma liver metastases.
      Preoperative computed tomographic features of the largest hepatic deposit were
      classified by the contour of advancing margin of the tumor into two types:
      lobular tumors with indentations with an acute angle and nonlobular tumors
      without such indentations. The correlation between computed tomographic features
      and 18 other clinicopathologic factors was examined. RESULTS: The overall five
      year survival rate was 34.1 percent. Of 85 hepatic tumors examined, 49 were
      lobular and 36 were nonlobular. Computed tomographic features correlated
      significantly with gross appearance (P = 0.007). Univariate analysis revealed
      that computed tomographic features (P < 0.0001), gross appearance (P = 0.0063),
      size of the largest hepatic deposit (P = 0.0075), age (P = 0.0140), and satellite
      lesions (P = 0.0443) were significant prognosticators. The five-year survival
      rates in patients with lobular and nonlobular tumors were 10.4 and 66.1 percent,
      respectively. By multivariate analysis, computed tomographic features (P <
      0.0001) and size of the largest hepatic deposit (P = 0.0419) were independently
      significant. CONCLUSIONS: Computed tomographic features of colorectal carcinoma
      liver metastases correlate with their gross appearance. The computed tomographic
      characterization of liver metastases is the most important independent prognostic
      factor in patients undergoing curative hepatectomy.

PMID- 11535857
TI  - Clinical application of continent anal plug in bedridden patients with
      intractable diarrhea.
AB  - PURPOSE: Some patients bedridden from various causes such as stroke or spinal
      cord injury experience poor control of bowel movement. This causes fecal leakage
      and diarrhea, increases the risk of perianal excoriation and bed sores, and is a
      burden on caregivers. To evaluate the efficacy of fecal evacuation and the
      prevention and treatment of skin complications in intractable diarrhea patients
      using a new device. METHODS: A continent anal plug (US Patent No. 5 569 216)
      comprises an inner balloon surrounded by an outer balloon, both of which are
      mounted on a silicone tube containing a pair of air passages and an enema fluid
      inlet. The tube is secured in place in the rectum by the inflatable outer balloon
      and is designed to drain fecal matter through a thin collapsible hose situated in
      the anal canal. Thirty-two patients (21 male; median age 61 (range, 28-76) years)
      were evaluated after fully informed consent. Median duration was 12 (range, 3-37)
      days. RESULTS: The continent anal plug evacuated efficiently in those patients
      with loose or watery stools who only required irrigation once daily or not at
      all. Skin excoriations improved in three to seven days. Minimal leakage was seen
      around the anus. There was no anorectal mucosal injury noted over 37 days.
      CONCLUSIONS: The continent anal plug is an efficient method of treating patients
      with loss of bowel control and incontinence because it enables controlled fecal
      evacuation and helps reduce skin complications without causing anorectal mucosal
      injury.

PMID- 11535856
TI  - Pelvic floor disturbance after childbirth: vaginal delivery damages the upper
      levels of sphincter innervation.
AB  - PURPOSE: Vaginal delivery disturbs pelvic floor innervation, which has previously
      been studied as a single mechanism. The effects of childbirth on innervation at
      different levels of the anal sphincter system were studied after childbirth.
      METHODS: Both anal manometry and motor latencies were measured in 67 females.
      Twenty-nine females (30.8 +/- 4.4 years) were examined four days after vaginal
      delivery. Eleven of these 29 females were re-examined five months after vaginal
      delivery. Nineteen females (33.6 +/- 4.6 years) who were examined five to nine
      days after undergoing an elective cesarean section and 19 asymptomatic,
      nonpregnant females (26.8 +/- 6.9 years) served as controls. Motor latencies were
      bilaterally measured within the anal sphincter system at 5, 3.8, 2.6, and 1.5 cm
      from the perineal skin by using a concentric needle electrode after sacral
      magnetic stimulation. Means of the bilateral latencies were analyzed. RESULTS: In
      postpartum females who gave birth vaginally, motor latencies at 5 and 3.8 cm,
      although not those at 2.6 and 1.5 cm, from the perineal skin were significantly
      prolonged, and anal pressure monitored by maximum resting and squeeze pressures
      was significantly decreased compared with that in control females. The decreased
      anal pressure normalized spontaneously. The prolonged motor latencies at the
      upper two levels of the anal sphincter system persisted in these females for five
      months after vaginal delivery. CONCLUSIONS: The disturbance of innervation of the
      upper anal sphincter system after vaginal delivery may last for a long time,
      whereas the decreased anal pressure normalizes in a short time. The protracted
      disturbance of innervation of the upper anal sphincter system may be associated
      with later development of fecal incontinence.

PMID- 11535858
TI  - Electromyography of the pelvic floor musculature in the assessment of obstructed
      defecation symptoms.
AB  - PURPOSE: The purpose of this study was to use electromyography to examine the
      behavior of the external sphincter, puborectalis muscle, and pubococcygeus muscle
      during attempted defecation in patients with symptoms of obstructed defecation
      and in normal subjects to highlight differences of clinical significance.
      METHODS: A total of 35 patients (31 females) aged 20 to 80 (mean, 53.7 +/- 13.3)
      years with unprepared bowel who had normal colon transit time and obstructed
      defecation symptoms and 12 voluntary control subjects (7 females) aged 23 to 68
      (mean, 48 +/- 11.5) years underwent an electromyography evaluation of the
      activity of the external sphincter, puborectalis muscle, and pubococcygeus muscle
      during attempted defecation. The patients were also examined in separate sessions
      with defecography and anal manometry. RESULTS: During attempted defecation,
      puborectalis muscle and external sphincter always reacted in the same manner.
      When evaluated with pubococcygeus muscle, three main patterns of activity were
      observed either in patients or in controls: 1) coordinated activation pattern; 2)
      coordinated inhibition pattern; and 3) uncoordinated or equivocal pattern:
      activation of pubococcygeus muscle with inhibition of puborectalis
      muscle/external sphincter, activation followed by inhibition of the three
      muscles, and activation followed by inhibition of pubococcygeus muscle and no
      change in the others. We never observed activation of puborectalis
      muscle/external sphincter concomitant with inhibition of pubococcygeus muscle.
      The inhibitory coordinated pattern occurred significantly (P = 0.01) more
      frequently in controls than in patients. These subjects also presented a
      significantly (P = 0.01) lower frequency of pubococcygeus muscle inhibition.
      CONCLUSIONS: Either activation or inhibition appears as a physiological behavior,
      possibly adopted in different circumstances, of the pelvic floor muscles during
      attempted defecation. The higher prevalence of coordinated inhibitory patterns in
      normal subjects and the lower frequency of pubococcygeus muscle inhibition in
      patients with symptoms of obstructed defecation, however, suggests that a loss of
      inhibition capacity progressing from pubococcygeus muscle to puborectalis
      muscle/external sphincter muscles could determine the insurgence of obstructed
      defecation symptoms in some subjects, who should therefore benefit from
      biofeedback retraining aimed at reacquisition of the inhibition capacity of all
      muscles of the pelvic floor during defecation.

PMID- 11535859
TI  - Intravenous metronidazole for the treatment of Clostridium difficile colitis.
AB  - PURPOSE: Severe Clostridium difficile colitis may produce abdominal distention
      and ileus, precluding oral antibiotic therapy. Stimulated by several case reports
      in which intravenous metronidazole was used, we reviewed our experience. METHODS:
      Using pharmacy and microbiology laboratory records, we retrospectively identified
      patients with C. difficile colitis who received intravenous metronidazole as
      initial monotherapy. To be included, patients had to fulfill the following
      criteria: 1) at least six doses (equivalent to two days of therapy) of
      intravenous metronidazole were administered, 2) no other potential cause for
      colitis was found, and 3) the diagnosis of C. difficile colitis was firmly
      established. For eligible patients, five clinical parameters were assessed before
      and after intravenous metronidazole. RESULTS: Our patient group (n = 10) received
      an average of 13.7 (range, 6-24) doses of intravenous metronidazole as initial
      therapy for C. difficile colitis. All received a dose of 500 mg three times
      daily. The majority of patients with vomiting, fever, and/or abdominal pain
      present at the beginning of therapy had resolution with intravenous
      metronidazole. Only one patient developed a symptom (vomiting) while on therapy;
      however, this eventually resolved when oral metronidazole was instituted. No
      patient required colectomy for refractory colitis or developed toxic megacolon.
      No patient, including those on prolonged courses, developed toxicity related to
      intravenous metronidazole such as peripheral neuropathy. CONCLUSIONS: Intravenous
      metronidazole may be effective therapy in patients with C. difficile colitis. A
      randomized, prospective study appears warranted.

PMID- 11535860
TI  - Comparison of electromagnetic field stimulation on the healing of small and large
      intestinal anastomoses.
AB  - PURPOSE: Magnetic fields have been shown to affect biologic processes.
      Accordingly, an experimental study was designed to investigate the effect of
      electromagnetic field stimulation on intestinal healing and to compare small and
      large intestinal anastomoses. METHODS: An ileal or a colonic anastomosis was
      constructed in rats. Beginning the day after surgery, randomly assigned groups
      were exposed to sinusoidal electromagnetic field stimulation of 10.76-mT
      intensity and 50-Hz frequency, with 2-hour-on/10-hour-off cycles. After seven
      days, intestinal anastomoses were assessed for hydroxyproline content and
      breaking strength. Statistical comparison between each experimental and control
      group yielded significance (P < 0.05) in all cases. RESULTS: Hydroxyproline
      content increased significantly in ileum from 1.650 +/- 0.11 (mean +/- standard
      error of the mean) to 2.036 +/- 0.11 microg/mg (P = 0.0249) and in colon from
      1.526 +/- 0.11 to 1.922 +/- 0.11 microg/mg (P = 0.0135). Breaking strength also
      increased significantly in ileum from 0.213 +/- 0.01 to 0.255 +/- 0.01 MPa (P =
      0.001) and in colon from 0.227 +/- 0.01 to 0.270 +/- 0.01 MPa (P = 0.006).
      CONCLUSIONS: Electromagnetic field stimulation provided a significant gain in
      anastomotic healing in both small and large intestine. There were no apparent
      differences detected between the healing of small and large intestinal
      anastomoses except for slight differences in the time sequences of events and
      magnitude. The study demonstrated a significant increase in both biochemical and
      mechanical parameters. Additional investigations are needed to determine optimal
      conditions and promote selective biologic responses.

PMID- 11535861
TI  - Effect of subtotal colectomy on gastric emptying of a solid meal in slow-transit
      constipation.
AB  - BACKGROUND: Idiopathic slow-transit constipation is considered a panenteral
      disease in which patients may have delayed gastric emptying. The effects of total
      abdominal colectomy and ileorectal anastomosis on upper gut motility are unknown.
      The aim of this study was to evaluate gastric emptying in patients with
      idiopathic slow-transit constipation before and after subtotal colectomy.
      METHODS: Gastric emptying of a solid meal was studied by scintigraphic technique
      in 11 patients with idiopathic slow-transit constipation. The total colonic
      transit time was more than 72 hours in all patients studied, with delay in
      transit in all segments of the colon. The gastric emptying test was repeated 3 to
      6 months after total abdominal colectomy and ileorectal anastomosis in ten of
      these patients. Before and after surgery, patients filled out a questionnaire to
      record upper gut symptoms. RESULTS: Solid gastric emptying was delayed (T1/2 >
      upper limit of normal) in 7 of 11 patients with idiopathic slow-transit
      constipation. Gastric emptying T1/2 was almost similar before and after surgery.
      Mean +/- standard deviation was 142 +/- 91 minutes before surgery and 146 +/- 67
      minutes after surgery. Symptoms of vomiting and belching improved significantly
      after surgery. Symptoms of nausea, bloating, and pyrosis also decreased, but
      these changes failed to reach statistical significance. CONCLUSION: Despite a
      reduction in upper gut symptoms, total abdominal colectomy and ileorectal
      anastomosis does not improve delayed gastric emptying in patients with idiopathic
      slow-transit constipation.

PMID- 11535862
TI  - The ileosigmoid knot: new observations and changing trends.
AB  - PURPOSE: Ileosigmoid knot is a rare surgical emergency. Most previous
      publications are either retrospective reviews of hospital records or sporadic
      case reports. Personal experience with this condition is often limited to one or
      two cases. This article describes the personal experience with this rare
      condition of a single author. This seems to be the largest reported prospective
      study of ileosigmoid knot. METHODS: Seven patients with ileosigmoid knot were
      treated during a period of three years. RESULTS: Ileosigmoid knot was common in
      males in their fourth decade. Mean duration of symptom was 22 hours. Correct
      preoperative diagnosis was possible in 71 percent of cases. The knot was
      successfully unraveled in 71 percent of cases. Sigmoid colon was gangrenous in
      all the patients (100 percent), whereas the ileum was gangrenous in only 43
      percent of cases. There was no correlation between duration of symptoms and
      incidence of gangrene. After resection of gangrenous intestine, primary
      anastomosis was done in all patients. There were no deaths. The mean hospital
      stay was 14 days. CONCLUSIONS: Correct preoperative diagnosis of ileosigmoid knot
      is possible when clinical, radiologic, and sigmoidoscopic features are considered
      together. Unraveling of the knot seems to be beneficial in ileosigmoid knot
      except when both components of the knot are frankly gangrenous. Primary
      anastomosis (ileoileal and/or colocolic) of resected gut seems to be a safe and
      better alternative in the management of ileosigmoid knot.

PMID- 11535863
TI  - Adverse effects of laxatives.
AB  - Laxatives are among the most commonly used drugs or additives. Most are quite
      safe when used judiciously, intermittently when possible, and in the absence of
      contraindications. Bulking agents and nonabsorbable compounds such as lactulose
      can cause bloating but have very few serious adverse effects except for the
      allergic reaction to psyllium preparations. Osmotic laxatives containing poorly
      absorbable ions such as magnesium or phosphate can cause metabolic disturbances,
      particularly in the presence of renal impairment. However, if taken
      intermittently, in the absence of conditions such as ileus or bowel obstruction,
      they have few adverse effects. Polyethylene glycol solutions are emerging as an
      effective and safe mode of treatment for chronic constipation. Of stimulant
      laxatives, senna compounds and bisacodyl are the most commonly used. Although
      there are data to support the neoplastic potential of this class of drugs in in
      vitro studies, epidemiologic data in humans so far has not established a clear
      link between these laxatives and colonic neoplasia. The link between stimulant
      laxatives and structural changes, such as the "cathartic colon" or enteric nerve
      damage, is not well established either. Danthron compounds should be avoided
      because of hepatotoxicity.

PMID- 11535864
TI  - Adenocarcinoma at the site of ileoanal anastomosis in Crohn's disease: report of
      a case.
AB  - PURPOSE: Proctocolectomy with ileoanal anastomosis has gained acceptance for the
      treatment of patients with ulcerative colitis. However, there are some patients
      with Crohn's disease who received ileoanal anastomosis, because some Crohn's
      colitis is difficult to differentiate from ulcerative colitis. The risk of cancer
      development at the site of ileoanal anastomosis has not been emphasized in
      Crohn's disease. METHODS: A 12-year-old patient with Crohn's disease was treated
      by proctocolectomy with straight ileoanal anastomosis. Twenty-five years after
      the operation, the patient noticed the tumor that developed at the site of
      ileoanal anastomosis. RESULTS: This article presents a patient with Crohn's
      disease who developed invasive adenocarcinoma at the site of ileoanal anastomosis
      25 years after proctocolectomy with ileoanal anastomosis. CONCLUSIONS: An
      ileoanal anastomosis does not eliminate the risk of cancer development, and
      surveillance after this operation seems advisable.

PMID- 11535865
TI  - Adenocarcinoma arising from along the rectal stump after double-stapled
      ileorectal J-pouch in a patient with ulcerative colitis: the need to perform a
      distal anastomosis. Report of a case.
AB  - Patients treated with restorative proctocolectomy for ulcerative colitis
      occasionally develop neoplasia from the rectal mucosal remnants. We report a case
      of a 65-year-old male who developed an adenocarcinoma from the rectal stump after
      a double-stapled ileorectal J-pouch for ulcerative colitis. We emphasize the need
      to perform the anastomosis either at the level of the dentate line or just
      cephalad to the anal transitional zone. Furthermore, when high-grade dysplasia at
      the rectum is evident, either an ileal pouch-anal anastomosis with mucosectomy or
      completion proctectomy with an end Brooke ileostomy should be offered. This is
      the second report in the literature of a carcinoma arising after use of the
      double-stapled ileal pouch-anal anastomotic technique.

PMID- 11535866
TI  - Postanal sphincter repair for anterior resection anal sphincter injuries: report
      of three cases.
AB  - Treatment options are limited for intractable excessive stool frequency and
      incontinence after low anterior resection for rectal cancer. Fortunately, this is
      quite rare, but three such patients were reported. The patients did not respond
      to two years of expectant treatment, including medications and anorectal
      biofeedback. Anorectal physiologic tests and endoanal ultrasound findings were
      consistent with internal anal sphincter injuries, which are known to occur with
      transanal insertion of stapling instruments. After postanal sphincter repair,
      stool frequency was reduced from 5.7 (standard error of the mean, 1.3) to 1.7
      (0.3) stools per day. Fecal incontinence requiring pads in all patients was
      reduced to full continence in two patients and gas incontinence in one.
      Continence score improved from 13.7 (2.2) to 1.3 (0.3). Mean follow-up was 3.2
      (0.5) years. Postanal sphincter repair could be considered when persistent bowel
      dysfunction after anterior resection is caused by internal sphincter injury.

PMID- 11535867
TI  - Ultrasound diagnosis of enteroceles.

PMID- 11535868
TI  - "Colonic coloplasty" equals "transverse coloplasty pouch made in Switzerland".

PMID- 11535870
TI  - Physical activity and cancer prevention -- is 'no pain, no gain' passe?

PMID- 11535869
TI  - Stapled hemorrhoidectomy in patients with prolapsed irreducible hemorrhoids.

PMID- 11535871
TI  - Oral contraceptives, cancer and vascular disease.

PMID- 11535872
TI  - Is type III intestinal metaplasia an obligatory precancerous lesion in intestinal
      type gastric carcinoma?
AB  - This retrospective study was performed to assess whether type III intestinal
      metaplasia is an obligatory precancerous lesion of intestinal-type gastric
      carcinoma and to determine its possible use as a marker of enhanced cancer risk.
      From 48 consecutive patients with gastric cancer who underwent a gastrectomy over
      a 3-year period (mean age 72.0 years; 29 M/19 F), at least two sections from
      antrum, corpus and tumour-surrounding mucosa were obtained for the examination of
      presence and subtypes of intestinal metaplasia (IM). It was found that 77.1% of
      the carcinomas were of the intestinal type and 22.9% of the diffuse type. The
      intestinal-type was more often found in males (P = 0.01); the mean age at
      diagnosis in this type was higher than in the diffuse cancer group (P = 0.004).
      There was a high prevalence of total IM in both the intestinal (75.7%) and
      diffuse group (88.9%). Type I IM was predominant in antrum and corpus of patients
      from both groups. Type III IM was only found among patients with intestinal-type
      carcinoma. However, its prevalence was rather low (26.3%). Therefore the absence
      of this lesion in patients with other risk factors cannot be used as an argument
      for lowering the degree of surveillance and its presence seems to be sufficient
      indication for long-term follow-up.

PMID- 11535873
TI  - Butyrate and propionate downregulate ERK phosphorylation in HT-29 colon carcinoma
      cells prior to differentiation.
AB  - We have characterized the effects of different short-chain fatty acids (SCFAs) on
      cell growth and differentiation as well as the phosphorylation state of ERK1 and
      2 in the human colon adenocarcinoma cell line HT-29. Of the five SCFAs tested,
      only butyrate and propionate impaired cellular proliferation. Moreover, butyrate
      and propionate specifically resulted in a decrease in ERK1 and 2 phosphorylation
      at 3 and 6 hours post-treatment, suggesting a correlation between the ability of
      these SCFAs to inhibit cellular proliferation and decrease ERK phosphorylation.
      Notably, the decrease in ERK phosphorylation was observed prior to the induction
      of the differentiation markers alkaline phosphatase (AP) and carcinoembryonic
      antigen (CEA) by butyrate and propionate from days 6 to 18 post-treatment. In the
      case of butyrate- and propionate-induced differentiation, ERK phosphorylation is
      a marker and may play a role in the proliferation and/or differentiation states
      of this cell line.

PMID- 11535874
TI  - Stage of extension and treatment for colorectal cancer after a negative test and
      among non-responders in mass screening with guaiac faecal occult blood test: a
      French experience.
AB  - Despite its proven efficacy in three randomized trials, the relevance of mass
      screening for colorectal cancer using the guaiac faecal occult blood test is
      still debated. The low sensitivity of the test and the poor participation rate,
      especially in France, are major obstacles to its effectiveness. The aim of our
      study was to characterize cancers occurring after a negative test and among non
      participants in the screening programme organized in the French department of
      Calvados. Cancers in the negative test group had a later stage of extension than
      subjects testing positively but an earlier stage of extension than cancers in the
      reference group, which were not different from those of non-responders. The
      proportion of resection for non-responders was significantly lower than that for
      participants, whatever the test result (P < 0.001), and lower than that for
      reference subjects (P < 0.05). There was no difference in treatment between
      negative and positive responders. Negative responders did not have a delayed
      cancer diagnosis or a worse condition of treatment than people who were not
      screened. Low sensitivity reduced the efficacy of colorectal cancer screening but
      did not seem to increase the potential to do harm.

PMID- 11535875
TI  - APACC, a French prospective study on aspirin efficacy in reducing colorectal
      adenoma recurrence: design and baseline findings.
AB  - Colorectal cancer is the second most frequent cause of death from cancer in
      western countries. Many lines of evidence suggest that non-steroidal anti
      inflammatory drugs (NSAIDs) may offer chemoprevention against colorectal cancer.
      A multicentre, double-blind, randomized, controlled trial is underway to
      determine the efficacy of regular aspirin intake (160 or 300 mg/day) in reducing
      colorectal adenoma recurrence. We now report the baseline characteristics of
      subjects enrolled into the trial. RESULTS: A total of 618 polyps were excised
      from 274 patients at the baseline colonoscopy. Men had on average (+/-SD) 2.5 +/-
      1.8 polyps per subject and women had 1.7 +/- 1.2. Ninety-one (33.7%) had three or
      more adenomas and 183 (67.8%) had more than one adenoma measuring 10 mm or more
      in diameter. The mean (+/-SD) age of the subjects was 57.7 (+/- 9.4) years. Sixty
      seven (24.9%) reported that they had previously had adenoma(s), 95 (35.2%)
      reported a family history of colorectal cancer and 41 (15.2%) a family history of
      colorectal adenomas. PERSPECTIVE: All subjects will undergo a one-year clearance
      colonoscopy by February 2001. Clinical, molecular biological and dietary data
      will enable us to investigate other factors influencing the recurrence of
      adenomas in this group of high-risk subjects.

PMID- 11535876
TI  - Beliefs, knowledge and attitudes as predictors of sunbathing habits and use of
      sun protection among Swedish adolescents.
AB  - In 1996, a random population sample of 2615 adolescents completed a questionnaire
      concerning habitual sun-related behaviours, attitudes towards sunbathing, and
      knowledge about skin cancer. Females, older adolescents, those with less sun
      sensitive skin, those with higher knowledge and those with a positive attitude
      towards sunbathing were more likely to be frequent sunbathers. Younger
      adolescents, those who today sunbathe moderately, and those with sensitive skin
      were more likely to believe that they would sunbathe more often in the future.
      Males, adolescents with less sensitive skin, those with a positive attitude
      towards sunbathing and those sunbathing often, were less likely to use protection
      when sunbathing. Interventions to decrease sun exposure among adolescents should
      focus on changing attitudes toward sunbathing and having a tan, since knowledge
      of skin cancer and the damaging affect of sunbathing did not seem to effect
      current sunbathing habits, or use of sun protection.

PMID- 11535877
TI  - Effect of selenomethionine on N-methylnitronitrosoguanidine-induced colonic
      aberrant crypt foci in rats.
AB  - An association between low selenium intake and the incidence or prevalence of
      cancers is well known. Selenium in the form of selenomethionine supplemented in
      drinking water has been found to be highly effective in reducing tumour incidence
      and preneoplastic foci during the development of hepatocarcinogenesis in rats in
      our previous studies. Here, an attempt has been made to investigate whether the
      dose and form of selenium found to be effective during hepatocarcinogenesis is
      equally effective in N-methylnitronitrosoguanidine-induced colorectal
      carcinogenesis in terms of antioxidant defence enzyme systems, DNA chain breaks
      and incidences of aberrant crypt foci. Treatment with selenomethionine either on
      initiation or on selection/promotion, or during the entire experiment showed that
      selenomethionine was most effective in regulating the cellular antioxidant
      defence systems, DNA chain break control and reducing aberrant crypt foci in the
      colorectal tissues of rats. Our results also confirm that selenium is
      particularly effective in limiting the action of the carcinogen during the
      initiation phase of this colorectal carcinogenesis, just as we found with
      hepatocarcinogenesis in our previous studies.

PMID- 11535878
TI  - Plant foods and risk of gastric cancer: a case-control study in Uruguay.
AB  - The association between plant foods intake and gastric cancer risk was
      investigated in a Uruguayan study on environmental factors and cancer. The study
      included 160 newly diagnosed and histologically verified cases of gastric
      carcinoma and 320 hospitalized controls. These controls were frequency-matched to
      the cases on age, sex, residence and urban/rural status. Total vegetable intake
      was associated with a reduction in risk (odds ratio (OR) 0.64, 95% confidence
      interval (CI) 0.38-1.08), which was markedly attenuated after adjustment for
      total fruit intake. The only group of vegetables that persisted as significantly
      protective after controlling for total energy and total fruit consumption were
      allium vegetables (OR 0.56, 95% CI 0.34-0.92). On the other hand, total fruit
      consumption displayed a strong inverse association after controlling for total
      vegetable intake (OR 0.35, 95% CI 0.21-0.59). Neither tubers nor pulses were
      associated with gastric cancer risk. Finally, total plant foods were strongly
      associated with a reduced risk of stomach cancer (OR 0.31, 95% CI 0.18-0.54). It
      is suggested that vitamins (vitamin C and carotenoids) and bioactive substances
      (diallyl sulfide) could be involved in the mechanisms of action of plant foods.

PMID- 11535879
TI  - Fruit and vegetable consumption in the prevention of oesophageal and cardia
      cancers.
AB  - The incidence of adenocarcinoma of the oesophagus has increased rapidly in recent
      decades. In order to appreciate the potential for prevention by means of dietary
      modification, we estimated the aetiological fractions and the increments in
      absolute risk attributable to low intake of fruit and vegetables for
      adenocarcinoma and squamous cell carcinoma of the oesophagus and for
      adenocarcinoma of the gastroesophageal junction. We conducted a nationwide
      population-based case-control study in Sweden, with participation of 608 cases
      and 815 controls. We used unconditional logistic regression to estimate relative
      risks, from which we calculated aetiological fractions. Individuals in the
      highest exposure quartile (median 4.8 servings/day) versus the lowest (median 1.5
      servings/day) showed approximately 50% lower risk of oesophageal adenocarcinoma
      and 40% lower risk of oesophageal squamous cell carcinoma, but no risk reduction
      for gastric cardia adenocarcinoma. Approximately 20% of oesophageal
      adenocarcinoma, and likewise squamous cell carcinoma, in Sweden was attributed to
      consuming less than three servings of fruit and vegetables per day. A very large
      number of individuals (over 25,000) would need to increase their fruit and
      vegetable consumption moderately in order to prevent one oesophageal cancer per
      year. Moderate relative risk reductions translate into weak absolute risk
      reductions for oesophageal cancers in Sweden.

PMID- 11535880
TI  - Trends in skin cancer incidence in Vaud: an update, 1976-1998.
AB  - Trends of skin cancer incidence by histotype in the Swiss Canton of Vaud (608,000
      inhabitants) between 1976 and 1992 were updated on the basis of 6720 further skin
      cancers registered over the period 1993-1998. Trends in the last period were
      downwards for squamous cell carcinoma in both sexes, still on the rise for basal
      cell carcinoma, and levelled off for malignant melanoma in females.

PMID- 11535881
TI  - International conference on dietary factors: cancer causes and prevention,
      Vienna, 14-17 February 2001.

PMID- 11535882
TI  - Decreasing incidence of all histological subtypes of oesophagus cancer in
      Tuscany, Italy.

PMID- 11535883
TI  - Oral and pharyngeal cancer: lack of prevention and early detection by health care
      providers.

PMID- 11535884
TI  - Clothes make the man.

PMID- 11535885
TI  - Practical utility of the D-dimer assay for excluding thromboembolism in severely
      injured trauma patients.
AB  - BACKGROUND: We have advocated the use of a D-dimer assay to exclude the diagnosis
      of pulmonary embolism (PE) and deep venous thrombosis (DVT) in surgical and
      trauma patients suspected of having these diagnoses. Injury is known to increase
      D-dimer levels independent of thromboembolism. The purpose of this study was to
      assess the period after injury over which the D-dimer assay remains positive
      because of injury exclusive of thromboembolism. METHODS: We prospectively sampled
      the plasma of severely injured patients for D-dimer using an enzyme-linked
      immunosorbent assay method at admission; at hours 8, 16, 24, and 48; and at days
      3, 4, 5, and 6. Patients were then screened for DVT with a routine duplex Doppler
      at day 7. Patients were followed for PE, adult respiratory distress syndrome, and
      disseminated intravascular coagulation. RESULTS: One hundred fifty-four patients
      (mean Injury Severity Score of 23) underwent a total of 1,230 D-dimer assays.
      Twenty-six (17%) had thromboembolism. Nine (6%) patients developed DVT, 2 (1%)
      developed PE, 13 (8%) developed disseminated intravascular coagulation, and 11
      (7%) developed severe adult respiratory distress syndrome. None of the trauma
      patients with thromboembolism had a (false) negative D-dimer at or after the time
      of their thromboembolic complication. True-negative D-dimer results as a function
      of time from injury are: 0 hours, 18%; 8 hours, 16%; 16 hours, 17%; 24 hours,
      22%; 48 hours, 37%; day 3, 34%; day 4, 32%; day 5, 30%; and day 6, 30%. The
      negative predictive value of the assay was 100%. D-dimer levels were
      significantly higher in those who developed a thromboembolic complication than in
      those who did not (independent of Injury Severity Score). CONCLUSION: These data
      serve to validate D-dimer as a means of excluding thromboembolism, specifically
      in patients with severe injury (100% negative predictive value). Before 48 hours
      after injury, however, the vast majority of these patients without
      thromboembolism had positive D-dimer assays. Because of the high false-positive
      rate early after severe injury, the D-dimer assay may be of little value before
      postinjury hour 48.

PMID- 11535886
TI  - Recombinant activated factor VII for adjunctive hemorrhage control in trauma.
AB  - BACKGROUND: Recombinant activated factor VII (rFVIIa) was approved for treatment
      of hemorrhages in patients with hemophilia who develop inhibitors to factors VIII
      or IX. Conditions with increased thromboembolic risk, including trauma with or
      without disseminated intravascular coagulation, were considered a
      contraindication for the drug. The mechanism of action of rFVIIa suggests
      enhancement of hemostasis limited to the site of injury without systemic
      activation of the coagulation cascade. Therefore, use of the drug in trauma
      patients suffering uncontrolled hemorrhage appears to be rational. METHODS: Seven
      massively bleeding, multitransfused (median, 40 units [range, 25-49 units] of
      packed cells), coagulopathic trauma patients were treated with rFVIIa (median,
      120 microg/kg [range, 120-212 microg/kg]) after failure of conventional measures
      to achieve hemostasis. RESULTS: Administration of rFVIIa resulted in cessation of
      the diffuse bleed, with significant decrease of blood requirements to 2 units
      (range, 1-2 units) of packed cells (p < 0.05); shortening of prothrombin time and
      activated partial thromboplastin time from 24 seconds (range, 20-31.8 seconds) to
      10.1 seconds (range, 8-12 seconds) (p < 0.005) and 79 seconds (range, 46-110
      seconds) to 41 seconds (range, 28-46 seconds) (p < 0.05), respectively; and an
      increase of FVII level from 0.7 IU/mL (range, 0.7-0.92 IU/mL) to 23.7 IU/mL
      (range, 18-44 IU/mL) (p < 0.05). Three of the seven patients died of reasons
      other than bleeding or thromboembolism. CONCLUSION: The results of this report
      suggest that in trauma patients rFVIIa may play a role as an adjunctive
      hemostatic measure, in addition to surgical hemostatic techniques, and provides
      the motivation for controlled animal and clinical trials.

PMID- 11535887
TI  - Reactive oxygen metabolites induce a biphasic contractile response in
      microvascular lung pericytes.
AB  - BACKGROUND: The changes in microvascular permeability characteristic of
      postinjury inflammation and sepsis may involve dysfunctional regulatory
      mechanisms at the capillary level. Pericytes, positioned abluminal to
      microvascular endothelium may, by their contractility, contribute to this
      regulation. Reactive oxygen metabolites (ROMs), well-known participants in lung
      inflammation, may exert an effect on pericytes, leading to changes in
      permeability and adult respiratory distress syndrome. This study investigates the
      effect of ROMs and antioxidants in an established in vitro assay of pericyte
      contractility. METHODS: Rat lung pericytes were cultured on collagen gel
      matrices. After exposure to the ROMs, the surface area of the collagen disks was
      digitally quantified (an integrated measure of cellular contraction) at 10 and 30
      minutes. The cells were exposed to hydrogen peroxide and pyrogallol at 10, 100,
      and 1,000 micromol/L. Antioxidant effects of catalase (100 micromol/L),
      superoxide dismutase (100 micromol/L), and pretreatment with vitamin E (1 mmol/L)
      were quantified. RESULTS: Hydrogen peroxide and pyrogallol induced concentration
      dependent relaxation at 10 minutes. Conversely, concentration-dependent
      contraction was seen at 30 minutes. Catalase completely attenuated both
      responses, whereas superoxide dismutase had no effect. Vitamin E had no effect at
      10 minutes but partially attenuated the contraction seen at 30 minutes.
      CONCLUSION: ROMs are capable of producing early relaxation and late contraction
      in cultured lung pericytes. Whereas catalase attenuates both responses, membrane
      bound vitamin E only partially attenuates late contraction. This suggests two
      separate mechanisms: early physiologic relaxation through signaling pathways
      affecting actin/myosin tone, and late membrane damage causing contraction. Either
      pathway may cause dysfunction in pulmonary capillary fluid regulation.

PMID- 11535888
TI  - CXCR2 regulation of tumor necrosis factor-alpha adherence-dependent peroxide
      production is significantly diminished after severe injury in human neutrophils.
AB  - BACKGROUND: Primed neutrophils are thought to play a key role in inflammatory
      pathology. We have shown though in vitro studies that interleukin (IL)-8 and
      growth-related oncogene-alpha (GROalpha) (CXCR2-specific chemokines) regulate the
      respiratory burst via the CXCR2 receptor. We have also shown in vivo, CXCR2
      receptors are down-regulated in severely injured patients. Our hypothesis is that
      regulation of the respiratory burst by CXCR2 is lost after severe injury.
      METHODS: Patient neutrophils were studied within 24 hours of admission to the
      hospital; excluded were severe head injury and patients with Injury Severity
      Score < 16. Patient and normal neutrophils were isolated by Ficoll-Hypaque
      centrifugation after dextran sedimentation. Neutrophils were plated with buffer,
      50 nmol/L IL-8 or GROalpha on fibronectin-coated plates for 15 minutes, then
      stimulated with 10 ng/mL of TNFalpha. CXCR2 expression was measured by flow
      cytometry. Receptor function was assessed by calcium mobilization. RESULTS: One
      female and 10 male patients with an average age of 37 +/- 3 and Injury Severity
      Score of 24 +/- 5 suffered blunt injury. CXCR2 showed a 32% +/- 7% loss, whereas
      CXCR1 showed 15% +/- 6% reduction. GROalpha stimulation of patient neutrophils
      showed 60% +/- 16% decrease in calcium mobilization, whereas IL-8 showed no
      decline. At 40 minutes, IL-8 and GROalpha significantly inhibited TNFalpha
      adherence-dependent peroxide production in normal neutrophils (35% +/- 4% and 45%
      +/- 3%, respectively; p < 0.05). Both IL-8 and GROalpha lost the ability to
      suppress the respiratory burst in severely injured patients, but GROalpha had a
      significantly greater loss of this suppression (p = 0.004). CONCLUSION: IL-8 and
      GROalpha lose the ability to regulate the TNFalpha-induced respiratory burst.
      This may contribute to neutrophil dysregulation after injury and result in organ
      injury.

PMID- 11535890
TI  - Early trauma polymorphonuclear neutrophil responses to chemokines are associated
      with development of sepsis, pneumonia, and organ failure.
AB  - OBJECTIVES: The modulation of polymorphonuclear neutrophil (PMN) function by
      injury is unpredictable, and can predispose either to hyperimmune states (adult
      respiratory distress syndrome [ARDS], multiple organ failure) or to immune
      dysfunction, infection, and sepsis. Such outcomes have been related to excess
      production of the CXC chemokine interleukin (IL)-8, but PMN responses to IL-8 are
      mediated by both the relatively stable and IL-8 specific CXC receptor 1 (CXCR1)
      and the labile, promiscuous CXCR2. We hypothesized that progression to septic and
      multiple organ failure outcomes could be related to early differences in PMN CXC
      receptor status. METHODS: PMNs were isolated 12 +/- 3 hours after injury from 15
      major trauma patients (Injury Severity Score of 34 +/- 2, 11 men and 4 women, age
      36 +/- 4 years) who survived at least 7 days. Volunteer normal PMNs (n = 6
      donors) were studied for comparison. Cells were stimulated either with the CXCR2
      specific agent growth-related oncogene-alpha, or with IL-8, which stimulates
      CXCR1 and CXRR2. Receptor response was assessed as the mobilization of cell
      calcium. The development of ARDS, sepsis, and pneumonia was assessed according to
      standardized criteria. Day 1 receptor activity in the clinical groups was then
      compared by analysis of variance with Tukey's or t tests as appropriate. RESULTS:
      In patients that were otherwise comparable, CXCR2 responses were markedly
      diminished in the PMNs of patients who went on to sepsis and pneumonia, but were
      elevated in PMNs from the patients who went on to ARDS. CXCR1 responses were
      modestly lower in trauma patients than volunteers, but showed no significant
      variations among the various clinical outcome groups. CONCLUSION: The activity of
      PMN CXCR2 receptors soon after injury may be reflected in the later clinical
      sequelae of PMN activity. High CXCR2 activity may correlate with PMN
      hyperfunction and outcomes such as ARDS, whereas the loss of CXCR2 function in
      inflammatory environments may impair PMN functions in a manner that predisposes
      to pneumonia or sepsis. Early responses of PMN CXC receptors to injury may
      influence the clinical course of trauma patients.

PMID- 11535891
TI  - Back to basics: validation of the admission systemic inflammatory response
      syndrome score in predicting outcome in trauma.
AB  - BACKGROUND: We have previously documented that the admission systemic
      inflammatory response syndrome (SIRS) score, calculated with four variables
      temperature, heart rate, neutrophil count, and respiratory rate-is a significant
      predictor of outcome in trauma (n = 4,887). The objective of this current study
      was to validate our previous findings in a larger trauma patient population, to
      analyze the predictive accuracy of the four individual components of the SIRS
      score (temperature, heart rate, neutrophil count, and respiratory rate), and to
      assess whether the admission SIRS score is an accurate predictor of intensive
      care unit (ICU) resource use in trauma. METHODS: Prospective data were collected
      on 9,539 patients admitted to a Level I trauma center over a 30-month period
      (January 1997-July 1999). Patients were stratified by age, sex, race, and Injury
      Severity Score (ISS). SIRS score was calculated at admission, and SIRS was
      defined as a SIRS score > or = 2. RESULTS: SIRS score was validated as a
      significant independent predictor of outcome in trauma by logistic regression
      analysis after controlling for age and ISS. Of the four SIRS variables,
      hypothermia (temperature < 36 degrees C) was the most significant predictor of
      mortality after controlling for age and ISS. Leukocytosis (neutrophil count >
      12,000/mm3) was the most significant predictor of total hospital length of stay.
      SIRS scores of > or = 2 were increasingly predictive of mortality and ICU
      admission by logistic regression analysis (p < 0.001). CONCLUSION: These data
      provide further validation that an admission SIRS score of > or = 2 is a
      significant independent predictor of outcome and ICU resource use in trauma.
      Temperature (hypothermia) is the individual component of the SIRS score with the
      greatest predictive accuracy. SIRS score should be calculated on all trauma
      admissions.

PMID- 11535892
TI  - Accuracy of administrative and trauma registry databases.
AB  - OBJECTIVE: Accurate data are needed to evaluate clinical outcomes, therapeutic
      modalities, and quality of care in trauma. Administrative data, usually used for
      billing, and trauma registries, have been used to perform these functions. This
      study compares data for trauma patients from administrative and trauma registry
      databases at a Level I trauma center. METHODS: Data from patients injured in 1998
      were obtained from both the trauma registry and administrative database. These
      International Classification of Diseases, Ninth Revision, Clinical Modification
      codes signify an admitting diagnosis of trauma. Patients from each database were
      "matched" by admission date, medical record number, age, and name. The two
      matched data sets were compared for accuracy in recording data. Chi-square
      analysis was used to compare groups. RESULTS: There were 2,702 patients found in
      both databases. One hundred eighteen patients with significant trauma were
      recorded in the trauma registry, but not in the administrative database.
      Comparison of recorded data for "matched" patients is as follows. The
      underreporting of mechanism of injury, diagnoses, diagnostic interventions,
      surgical procedures, and complications was rampant throughout the administrative
      database. Statistical significance was seen in the comparison between the trauma
      registry and the administrative database with motor vehicle collisions (458 vs.
      391), abdominal injuries (346 vs. 293), orthopedic injuries (1,243 vs. 1,101),
      and thoracic injuries (486 vs. 397). Diagnostic interventions such as diagnostic
      peritoneal lavage, head computed tomographic scans, and abdominal computed
      tomographic scans were all grossly underrecorded, with only 40%, 12%, and 9%
      captured by the administrative database, respectively. Analysis of surgical
      procedures revealed these same trends, with statistical significance seen in
      abdominal and orthopedic procedures. Complications such as acute respiratory
      distress syndrome and deep venous thrombosis showed statistically significant
      differences. Mortality was underreported in the administrative database, with 14
      deaths omitted. CONCLUSION: This study shows that administrative data have
      copious omissions of specific injuries, diagnostic and therapeutic interventions,
      as well as complications. The trauma registry recorded more of the diagnoses,
      diagnostics, procedures, and outcomes in the care of trauma patients. Trauma
      registries may be more useful than administrative databases in assessing quality
      of care and diagnostic and therapeutic interventions.

PMID- 11535893
TI  - Factors influencing pediatric injury in side impact collisions.
AB  - BACKGROUND: Side impact collisions pose a great risk to children in crashes, but
      information about the injury mechanisms is limited. METHODS: This study involves
      a case series of children in side impact collisions who were identified through
      Partners for Child Passenger Safety, a large, child-focused crash surveillance
      system. The aim of the current study was to use in-depth crash investigations to
      identify injury mechanisms to children in side impact collisions. RESULTS: Ninety
      three children in 55 side impact crashes were studied. Twenty-three percent (n =
      22) of the children received an Abbreviated Injury Scale (AIS) score > or = 2
      (clinically significant) injury. In these 22 children, head (40%), extremity
      (23%), and abdominal injuries (21%) were the most common significant injuries.
      Cases that illustrate body region-specific injury mechanisms are discussed.
      CONCLUSION: The cases revealed that serious injuries, particularly head injuries,
      occur even in minor crashes, and efforts should be made to make the interiors of
      vehicles more child occupant friendly. Lower extremity and abdominal injuries
      occurred because of contact with the intruding door. Design of vehicles to
      minimize crush should mitigate the occurrence and severity of these injuries.

PMID- 11535894
TI  - Outcome of adolescent trauma admitted to an adult surgical intensive care unit
      versus a pediatric intensive care unit.
AB  - BACKGROUND: Institutional protocol designates the adult trauma service as the
      primary manager of all adolescent traumas (age 14-18 years) unless admission to
      the pediatric intensive care unit (PICU) occurs. In the PICU, primary care
      becomes the responsibility of the pediatric intensivist, with trauma service as a
      consultant. The purpose of this study was to identify differences in the
      management of adolescent trauma between the pediatric intensivist in the PICU,
      and the adult trauma team in the surgical intensive care unit (SICU). METHODS:
      From January 1993 to January 1998, the medical records of all adolescent trauma
      patients requiring intensive care unit (ICU) management were reviewed. Depending
      on bed availability, patients younger than 16 were admitted to the PICU, and
      those 16 or older to the SICU. Demographic data obtained were age, sex, race,
      mechanism of injury, length of stay (LOS), ICU length of stay, days on mechanical
      ventilation, intubation, tracheotomy, intracranial pressure monitor, and Swan
      Ganz catheter placement. Home discharge, rehabilitation placement, and death were
      recorded. Morbidity was measured using Injury Severity Score methodology,
      Pediatric Trauma Score, and Pediatric Risk of Mortality. RESULTS: One hundred
      nine completed records were reviewed (SICU, n = 58; PICU, n = 51). There was no
      statistical difference in sex, race, mechanism of injury, ICU LOS, tracheotomy,
      and intracranial pressure monitor placements. There was no difference in
      morbidity, as measured by Injury Severity Score, Pediatric Trauma Score, and
      Pediatric Risk of Mortality score or in outcome measurements (death,
      rehabilitation placement). SICU patients were older (SICU, 16.9 +/- 1.0 years;
      PICU, 15.4 +/- 1.0 years; p < or = 0.1 Mann-Whitney U test), more likely to be
      intubated (SICU, n = 42; PICU, n = 24; p < or = 0.05 Fisher's exact test), more
      likely to have pulmonary artery catheter placement (SICU, n = 7; PICU, n = 0),
      and had longer LOS (SICU, 12.2 +/- 10.6; PICU, 9.8 +/- 14.1; p < or = 0.03 Mann
      Whitney U test). CONCLUSION: Adolescent trauma patients admitted to the PICU were
      less likely to be intubated or have a Swan-Ganz catheter placed. They had
      decreased LOS and days of mechanical ventilation. There was no difference in
      outcome measurements.

PMID- 11535895
TI  - Epidemiology of severe brain injuries: a prospective population-based study.
AB  - BACKGROUND: The aim of this prospective study was to estimate annual incidences
      of hospitalization for severe traumatic brain injury (TBI) (maximum Abbreviated
      Injury Score in the head region [HAIS] 4 or 5) in a defined population of 2.8
      million. METHODS: Severe TBI patients were included in the emergency departments
      in the 19 hospitals of the region. A prospective data form was completed with
      initial neurologic state, computed tomographic scan lesions, associated injuries,
      length of unconsciousness, and length of stay in acute care centers. Outcome at
      the time the patient left acute hospitalization was retrospectively assessed from
      medical notes. RESULTS: During the 1-year period (1996), 497 residents fulfilled
      the inclusion criteria, leading to an annual incidence rate of 17.3 per 100,000
      population; 58.1% were HAIS5. Mortality rate was 5.2 per 100,000. Men accounted
      for 71.4% of cases. Median age was 44 years, with a quarter of patients more than
      70 years old. Traffic accidents were the most frequent causes (48.3%), but falls
      accounted for 41.8% of all patients. Age and severity were different according to
      the major categories of external causes. In HAIS5 patients, 86.5% were considered
      as comatose (coma lasting more than 24 hours or leading to immediate death) but
      only 60.9% had an initial Glasgow Coma Scale score < 9. In the HAIS4 group, 7.2%
      had an initial Glasgow Coma Scale score < 9. Fatality rates were 30.0% in the
      whole study group, 7.7% in HAIS4, 12.8% in HAIS5 without coma, and 51.2% in HAIS5
      with coma. CONCLUSION: This study shows a decrease in severe TBI incidence when
      results are compared with another study conducted 10 years earlier in the same
      region. This is because of a decrease in traffic accidents. However, this results
      in an increase in the proportion of falls in elderly patients and an increase in
      the median age in our patients. This increased age influences the mortality rate.

PMID- 11535896
TI  - Arterial hypertension increases intracranial pressure in cat after opening of the
      blood-brain barrier.
AB  - BACKGROUND: Increased permeability for small solutes in brain capillaries means
      that a change in hydrostatic capillary pressure may influence transcapillary
      fluid exchange according to the Starling fluid equilibrium, and a high arterial
      pressure may cause transcapillary fluid filtration and raised intracranial
      pressure. This could be of clinical relevance in states of disrupted blood-brain
      barrier such as meningitis and after a severe head injury, especially since these
      patients quite often are spontaneously hypertensive, and hypertensive therapy is
      sometimes used to increase cerebral perfusion pressure. This study on cat
      investigated the long-term relation between arterial pressure and intracranial
      pressure in a state of disrupted blood-brain barrier. METHOD: Endotoxin was given
      intrathecally to open the blood-brain barrier and depress cerebral
      autoregulation. Arterial pressure was increased by about 30 mm Hg during 5 hours
      by dopamine and angiotensin II infusion. The immediate fall in intracranial
      pressure after normalization of blood pressure reflects the blood volume
      component of an intracranial pressure increase. RESULTS: Increased arterial
      pressure had no effect on intracranial pressure before endotoxin. Endotoxin
      infusion increased intracranial pressure from the normal value of 10 to 12 mm Hg.
      and at steady state by almost 10 mm Hg. Intracranial pressure increased further
      after the arterial pressure increase. At steady state (achieved within 5 hours),
      this increase was almost as great as the arterial pressure increase, and about
      80% persisted when measured directly after normalization of the arterial
      pressure. CONCLUSION: Increased arterial pressure in a state of disrupted blood
      brain barrier increases intracranial pressure, mainly because of brain edema.
      This stresses that arterial hypertension may be deleterious in conditions such as
      meningitis or after a brain trauma.

PMID- 11535898
TI  - Surgery induces human mononuclear cell arginase I expression.
AB  - BACKGROUND: Arginase is a metabolic enzyme for the amino acid arginine that
      participates in the immune response to trauma. We hypothesize that surgical
      trauma induces arginase expression and activity in the human immune system.
      METHODS: Peripheral mononuclear cell (MNC) arginase activity and expression and
      plasma nitric oxide metabolites and interleukin (IL)-10 were measured in patients
      undergoing elective general surgery. Twenty-two healthy volunteers served as a
      comparison population. RESULTS: MNC arginase activity increased within 6 hours of
      surgery (p < 0.05) and coincided with increased arginase I protein expression.
      Plasma nitric oxide metabolites decreased significantly postoperatively (p <
      0.05). Patients lacking an elevation in IL-10 failed to demonstrate increased MNC
      arginase activity. CONCLUSION: Increased MNC arginase expression may contribute
      to postsurgical immune dysfunction by affecting arginine use and availability and
      nitric oxide metabolism in the immune system. Plasma IL-10 may play a role in
      regulating MNC arginase activity.

PMID- 11535899
TI  - Use of enhanced stimulation voltage to determine the severity of compressive
      peripheral nerve injury.
AB  - BACKGROUND: The aim of this study was to investigate whether enhanced stimulation
      voltage could be a predictor of the extent of injury in acute compressive
      peripheral nerve trauma. METHODS: The femoral nerves were exposed on both sides,
      in 11 anesthetized rabbits. Supramaximal stimulation voltage was used to produce
      a maximal-amplitude compound muscle action potential (CMAP) from the quadriceps
      femoris muscle. Afterward, the left femoral nerve was clipped for 1 minute, and
      the right femoral nerve for 5 minutes to produce an acute compressive injury.
      Immediately after removal of the clip, the proximal and distal sides of the
      clippage site were stimulated by gradually increased voltage until CMAPs were
      obtained. The same procedure was repeated at the 30th and 60th minutes. The ratio
      of the CMAP amplitudes obtained from proximal and distal stimulation was measured
      to establish a classification. RESULTS: The stimulation voltages and amplitudes
      of the CMAPs before clippage were similar with the after-clippage values obtained
      from distal stimulation (p > 0.05), but the after-clippage values obtained from
      proximal stimulation were different in both sides (p < 0.05). Doubled stimulation
      voltage was enough to obtain CMAPs on the left side, but eightfold the initial
      level was required on the right side. The amplitude ratios recovered to preinjury
      levels in all of the subjects on the left side, but only two showed recovery on
      the right side (p < 0.001). Histopathologically, there was axonal compression
      without discontinuity on the left side, whereas the fibers were dispersed on the
      right side. CONCLUSION: Stimulation voltage was found to discriminate the
      severity of the lesion in experimental peripheral nerve injury. Proximal to
      distal amplitude ratio seems to be a prognostic factor when the injury is less
      severe.

PMID- 11535901
TI  - Changes in the local blood and lymph microcirculation in response to direct
      mechanical trauma applied to leg: in vivo study in an animal model.
AB  - BACKGROUND: The aim of this study was to investigate changes in the blood
      microcirculation of skin, subcutaneous tissue, and striated muscle, and the
      venous and lymphatic outflow from hind limb, after a standardized mechanical
      trauma. METHODS: Trauma, defined as 50% of the minimal energy needed for tibia
      fracture (3.7 J/g), was applied to the leg of hairless mice. Intravenously
      injected fluorescein isothiocyanate-dextran 150 kDa and Rhodamine-6G were used
      for intra-vital fluorescence microscopy of blood vessels. Lymphatics were stained
      with fluorescein isothiocyanate-dextran injected into the footpad. A computer
      assisted analysis system allowed measurement of the functional capillary density
      (FCD), vessel diameters, velocity of blood flow, and edema value expressed as
      extravasation index (EV). The percentage of slowly rolling and sticking
      leukocytes in postcapillary venules was estimated. RESULTS: At the site of
      injury, trauma resulted in significant reduction of FCD in skin, subcutaneous
      tissue, and striated muscle. There were no significant differences in the vessel
      diameter (skin subcutaneous and muscle arterioles and venules, and superficial
      saphenous artery and vein) or velocity of blood flow (subcutaneous tissue and
      muscle venules). The EV increased significantly in muscle venules and was higher
      in muscles, subcutaneous tissue, and superficial saphenous veins than in controls
      (nonsignificantly). An increased percentage of slowly rolling and sticking
      leukocytes was noted in the superficial saphenous vein at the site of injury and
      proximal to it. The lymphatics remained patent, with faster visualization and
      increased summarized cross-sectional areas in traumatized extremities.
      CONCLUSION: Early changes occurring in soft tissues in response to mechanical
      injury were characterized by reduction in FCD of skin and muscles, and less in
      subcutis; increased EV, reflecting leakage of macromolecules; increased
      percentage of slowly rolling and sticking leukocytes; maintenance of lymphatic
      vessel continuity; and increased lymph formation and flow rate.

PMID- 11535902
TI  - Thromboprophylaxis with 60 mg enoxaparin is safe in hip trauma surgery.
AB  - BACKGROUND: Little information is available concerning dosage and optimal
      initiation of thromboprophylactic therapy with low-molecular-weight heparin
      (enoxaparin) in nonelective hip surgery. The aim of our prospective study was to
      evaluate the incidence of clinically apparent deep vein thrombosis (DVT),
      pulmonary embolism (PE), and major hemorrhage in patients receiving
      thromboprophylaxis with enoxaparin undergoing hip surgery after hip fracture.
      METHOD: From 946 consecutive patients admitted with hip fractures, 897 were
      operated on and received enoxaparin according to the following regimen:
      Preoperative heparinization from time of admission onwards. Administration of 60
      mg enoxaparin, in two doses (20 and 40 mg subcutaneously), during the first 5
      days postoperatively. Prophylaxis for a minimum of 5 weeks (40 mg daily).
      RESULTS: Clinical signs of DVT were present in 37 patients (4.2%), who all
      underwent venography. In five patients, DVT was confirmed (0.6%). None of these
      patients suffered from PE. Another four patients (0.4%) developed clinical signs
      of PE, and suspected diagnosis was confirmed by computed tomographic scan in two
      (0.2%). No deaths because of PE were observed. Major hemorrhage occurred in 42
      patients (4.7%), there was one death from hemorrhage caused by an intracerebral
      event. No case of heparin-induced thrombocytopenia type II was observed.
      CONCLUSION: Thromboprophylaxis with 60 mg enoxaparin daily, in split doses,
      starting before surgery, is safe and appropriate in patients with hip fractures.
      Clinically apparent DVT and PE are rarely observed, and bleeding complications
      are comparable to those occurring with a conventional thromboprophylactic
      regimen.

PMID- 11535903
TI  - Treatment of distal clavicle fracture using Kirschner wires and tension-band
      wires.
AB  - BACKGROUND: Nonunion frequently follows distal clavicle fracture. Traditional
      pinning methods using the through acromioclavicular articulation may result in
      osteoarthritic changes or ankylosis. This study introduces a direct pinning
      technique in which the acromioclavicular joint is spared. METHODS: Twelve
      patients with displaced distal clavicle fractures received open reduction and
      fixation with Kirschner wires (K-wires) and tension-band wires, from May 1996 to
      March 1997. The indication for surgery was type IIa fracture or fracture with
      displacement. Unrestricted passive and active range of motion was performed as
      soon as possible after the operation. Stretching and exertional exercises were
      permitted after radiographs showed an osseous union and after the implants were
      removed. RESULTS: Eleven patients achieved osseous union with painless full
      motion. Union time ranged from 3 to 6 months. One patient suffered from more
      comminuted fracture because of a fall 2 months after operation. This patient
      received a revision surgery with distal clavicle resection and coracoclavicle
      reconstruction. Symptomless ossification around the coracoclavicle ligament was
      noted on radiographs in one patient. The ossification did not progress after the
      9-month follow-up. CONCLUSION: Edwards reported a rate of 45% delayed union and
      30% nonunion in type II fractures. Several techniques had been described in the
      relevant literature. In our practice, fixation with Kirschner wires and tension
      band wires has been successful in the treatment for displaced distal clavicle
      fracture.

PMID- 11535904
TI  - The role of interventional radiology in the management of blunt renal injury: a
      practical protocol.
AB  - OBJECTIVE: The purpose of this study was to evaluate the efficacy of a protocol
      designed to minimize the need for surgery in the management of severe blunt renal
      injury. METHODS: Forty-six of 752 trauma patients had evidence of renal injury on
      computed tomographic (CT) scan. Two patients required emergency laparotomy, and
      the remaining 44 patients were classified by CT scan grade using the American
      Association for the Surgery of Trauma classification system. Patients with CT
      scan grade 3 or over underwent renal angiography. RESULTS: Twenty-one patients
      had a high-grade injury on CT scan (> or =3). Eight had angiographic evidence of
      extravasation from renal arterial branches and underwent transarterial
      embolization. One patient with a grade 5 injury had extravasation from a main
      renal vein and underwent immediate laparotomy. This was the only patient who
      required surgery for renal injury. CONCLUSION: Surgery can be avoided in most
      cases of blunt renal injury. Hemodynamic instability and injury to main renal
      veins remain indications for surgical exploration.

PMID- 11535905
TI  - A new approach to extraperitoneal rectal injuries: laparoscopy and diverting loop
      sigmoid colostomy.
AB  - BACKGROUND: Current management of extraperitoneal rectal injuries involves a
      laparotomy and diversion of the fecal stream. In this study, we review our
      experience with laparoscopy and diverting loop sigmoid colostomy without
      laparotomy in the management of these injuries. METHODS: All patients admitted to
      the trauma unit at Groote Schuur Hospital between January 1995 and May 2000 with
      a rectal injury were evaluated. The presence of a rectal injury was confirmed by
      rectal examination and proctosigmoidoscopy. Intraperitoneal injuries were
      excluded by laparoscopy. Only patients who did not have intraperitoneal injuries
      were included in the study. The patients were then managed with a diverting loop
      sigmoid colostomy created through an abdominal wall trephine without laparotomy.
      RESULTS: Ten patients were included in the study. In eight patients, laparoscopy
      excluded intraperitoneal injuries. All 10 patients had a diverting loop sigmoid
      colostomy fashioned. There were no complications related to either the rectal
      injury or colostomy. Nine stomas have since been closed. CONCLUSION: In patients
      with isolated extraperitoneal rectal injuries, laparoscopic exclusion of
      intraperitoneal injuries, followed by a diverting loop sigmoid colostomy, is a
      feasible option.

PMID- 11535906
TI  - Incidence of pneumothorax from intercostal nerve block for analgesia in rib
      fractures.
AB  - BACKGROUND: The incidence of pneumothorax (PTX) after individual intercostal
      nerve block (INB) for postoperative pain reportedly varies from 0.073% to 19%.1-3
      This study investigated the incidence of PTX after INB for rib fractures.
      METHODS: We conducted a retrospective chart review of patients admitted between
      January 1996 and December 1999 with rib fractures who received INB. RESULTS: One
      hundred sixty-one patients received 249 intercostal nerve block procedures
      (INBPs). An INBP is one session where a set of intercostal nerves are blocked. A
      total of 1,020 individual intercostal nerves were blocked. There were 14
      pneumothoraces. The overall incidence of PTX per patient was 8.7%, with an
      incidence of PTX per INBP of 5.6%. The incidence of PTX was 1.4% for each
      individual intercostal nerve blocked. CONCLUSION: The incidence of PTX per
      individual intercostal nerve blocked is low. INB is an effective form of
      analgesia, and for most patients with rib fractures one INBP is sufficient to
      allow adequate respiratory exercises and discharge from the hospital.

PMID- 11535907
TI  - Association of hyperglycemia with increased mortality after severe burn injury.
AB  - BACKGROUND: Hyperglycemia is commonly associated with the hypermetabolic stress
      response. However, persistent hyperglycemia may adversely affect wound healing
      and immunity. The purpose of this study was to assess any relationship between
      hyperglycemia and clinical outcome after severe burn injury. METHODS: Survey of
      the medical records from January 1996 to July 1999 identified 58 pediatric
      patients with burns > or = 60% body surface. Patients were categorized as having
      poor glucose control (n = 33) if > or = 40% of all plasma glucose determinations
      were > or = 7.8 mmol/L (140 mg/dL) and compared with patients deemed to have
      adequate glucose control (n = 25) in whom > or = 40% of all glucose values were >
      or = 7.8 mmol/L. RESULTS: Despite similar age, burn size, caloric intake, and
      frequency of wound infection, patients categorized with poor glucose control had
      a significantly greater incidence of positive blood cultures (positive blood
      cultures/length of stay days, 0.42 +/- 0.04 for hyperglycemia patients vs. 0.30
      +/- 0.03 for normoglycemia patients; mean +/- SEM, p > or = 0.05). This finding
      was especially prominent for blood cultures positive for yeast. Hyperglycemia
      patients had significantly less percentage of skin graft take than did the
      normoglycemic patients (percent take/operative procedure, 64 +/- 9 for
      hyperglycemia patients vs. 88 +/- 5 for normoglycemia patients; p < 0.05). Nine
      patients (27%) with persistent hyperglycemia died compared with only one death
      (4%) in patients with adequate glucose control (p > or = 0.05). CONCLUSION: This
      association between poor glucose control, bacteremia/fungemia, reduced skin graft
      take, and subsequent mortality in severely burned children may be related to a
      hyperglycemia-induced detriment in antimicrobial defense. Although this report
      fails to establish cause and effect, these findings suggest that aggressive
      maneuvers to normalize plasma glucose in critically injured patients may be
      warranted.

PMID- 11535908
TI  - Does the presence of ultrasound really affect computed tomographic scan use? A
      prospective randomized trial of ultrasound in trauma.
AB  - OBJECTIVE: There is a paucity of evidence demonstrating that emergency department
      (ED) ultrasound changes clinical practice in trauma patients. We hypothesized
      that the presence of ultrasound would affect clinical decision making as
      evidenced through abdominal computed tomographic (CT) scan use in blunt multiple
      trauma patients. METHODS: This study used a prospective randomized format in an
      urban county ED with Level II trauma center status (ED census, 72,000 patients
      per year). Participants were patients with multiple blunt injuries meeting trauma
      center triage criteria. Patients were randomized to receive either abdominal
      ultrasound or no ultrasound (control) during initial ED resuscitation. The
      primary outcome variable was use of abdominal CT scan in patients with and
      without ultrasound. RESULTS: Two hundred eight patients were enrolled. The mean
      age was 40 +/- 18 years, and 62% were men. Mechanism of injury was motor vehicle
      crash, 56%; automobile versus pedestrian, 18%; motorcycle crash, 16%; falls, 10%;
      and other, 10%. One hundred four ultrasound and 104 control patients were
      analyzed. There were no apparent differences between ultrasound and control
      groups in demographics, injury type, or Injury Severity Score. Fifty-four of 104
      (52%) of the control group received abdominal CT scans versus 37 of 104 (36%)
      abdominal CT scans for the ultrasound group; mean difference in proportions was
      15.9 (p < 0.01; 95% confidence interval, 2.6-29.1). CONCLUSION: In this trial,
      the routine use of abdominal ultrasound in the evaluation of patients with
      multiple blunt injuries resulted in significantly fewer abdominal CT scans being
      obtained. A larger trial is needed to more clearly define the clinical and
      financial impact of ultrasound in the management of blunt abdominal trauma.

PMID- 11535909
TI  - The injured intoxicated driver: analysis of the conviction process.
AB  - BACKGROUND: The widespread nature of alcohol-related motor vehicle collisions
      suggests inadequacies in the system for deterring alcohol use when driving. This
      study was performed to determine whether hospitalization is a component in a
      "system failure" that allows injured, alcohol-impaired drivers to escape arrest
      and conviction for driving under the influence (DUI). METHODS: We conducted a
      retrospective review of medical and court records of intoxicated drivers injured
      in a motor vehicle collision who were transported to our Level I trauma center
      from January 1, 1997, through December 31, 1998. RESULTS: Of the 213 intoxicated
      drivers in our study, 172 (81%) were followed up by law enforcement officials,
      and 156 (73.2%) were arrested for DUI. Of those who were arrested and completed
      court hearings, 135 (93.8%) were convicted for DUI. CONCLUSION: These values are
      higher than those reported in previous studies and indicate that hospitalization
      does not "protect" injured, intoxicated drivers in our community.

PMID- 11535910
TI  - Epidemic increases in cocaine and opiate use by trauma center patients:
      documentation with a large clinical toxicology database.
AB  - BACKGROUND: Although reports have documented alcohol and other drug use by trauma
      patients, no studies of long-term trends have been published. We assessed
      substance use trends in a large cohort of patients admitted to a regional Level I
      adult trauma center between July 1984 and June 2000. METHODS: Positive toxicology
      results, collected via retrospective database review, were analyzed for patients
      admitted directly to the center. Data were abstracted from a clinical toxicology
      database for 53,338 patients. Results were analyzed for alcohol, cocaine, and
      opiates relative to sex, age (< 40/> or = 40 years), and injury type
      (nonviolence/violence). Positive toxicology test result trends were assessed for
      the 3 years at the beginning and end of the period (chi2). Testing biases were
      assessed for sex, race, and injury type. RESULTS: The patient profile was as
      follows: men, 72%; age < 40 years, 69%; nonviolence victims, 77%. Alcohol
      positive results decreased 37%, but cocaine-positive and opiate-positive results
      increased 212% and 543%, respectively (all p < 0.001). Cocaine-positive/opiate
      positive results increased 152%/640% for nonviolence and 226%/258% for violence
      victims, respectively (all p < 0.001). In fiscal year 2000, cocaine-positive and
      opiate-positive results were highest among violence victims (27.4% for both
      drugs). Cocaine-positive and opiate-positive results among nonviolence victims
      were 9.4% and 17.6%, respectively. Patients who were minorities or victims of
      violence were not tested more frequently than other patients. CONCLUSION:
      Epidemic increases in cocaine and opiate use were documented in all groups of
      trauma patients, with the greatest increases being in violence victims. Alcohol
      use decreased for all groups.

PMID- 11535911
TI  - Laryngeal trauma mimicking croup.

PMID- 11535912
TI  - Complete cervical tracheal transection from blunt trauma.

PMID- 11535913
TI  - An adult bilateral atlantoaxial rotary dislocation caused by airbag inflation.

PMID- 11535914
TI  - An unstable circumferential skull base fracture.

PMID- 11535915
TI  - Posttraumatic cervical epidural hematoma associated with congenital absence of a
      cervical spine pedicle: case report and literature review.

PMID- 11535916
TI  - Simultaneous dual posttraumatic diaphragmatic and abdominal wall hernias.

PMID- 11535917
TI  - Endovascular stent-graft placement for thoracic aortic injury: case report.

PMID- 11535918
TI  - Duodenal mucosal injury caused by blunt abdominal trauma.

PMID- 11535919
TI  - Conservative management of an uncommon renal foreign body secondary to explosion
      injury.

PMID- 11535920
TI  - Adrenal crisis after traumatic bilateral adrenal hemorrhage.

PMID- 11535921
TI  - Micronutrient supplementation in the critically ill patient: strategies for
      clinical practice.

PMID- 11535922
TI  - Dive tank explosion amputation.

PMID- 11535923
TI  - Magnetic resonance venography to evaluate deep venous thrombosis in patients with
      pelvic and acetabular trauma.

PMID- 11535924
TI  - What is actually needed to care for the critically injured patient?

PMID- 11535927
TI  - CD4/CD8 lymphocytes in BALF during the efferent phase of lung delayed-type
      hypersensitivity reaction induced by single antigen inhalation.
AB  - BACKGROUND: The precise mechanisms involved in the pathogenesis of
      hypersensitivity pneumonitis (HP) have not been identified. HP is characterized
      by inflammatory lymphocytic alveolitis and a remarkable increase in T-lymphocytes
      detected in bronchoalveolar lavage fluid (BALF). It is suggested that both CD4+
      and CD8+ T cells may contribute to the pathogenesis of HP. Experiments on animal
      models suggest that cell mediated immunity (CMI) is more important for the
      pathogenesis of HP than complex-mediated immunity, but the relationship between
      the subsets of BALF lymphocytes and humoral or cell-mediated allergic reactions
      is still not clear. The aim of our study was distinguish CD4+ and CD8+ T cells in
      BALF lymphocytes during a delayed-type hypersensitivity (DTH) reaction in the
      lung. MATERIAL AND METHODS: The experiment was performed on guinea pigs
      sensitized with BCG vaccine and subjected to a single inhalation of tubercle
      bacilli antigens (tuberculin). 24 hours after tuberculin provocation (at the time
      of maximum lymphocyte infiltration), bronchoalveolar lavage was performed on both
      sensitized and non-sensitized (control) animals. The total cell count was
      estimated, and a differential microscopical examination of BAL-fluid cells was
      performed, along with the phenotyping of BALF lymphocytes (by flow cytometry).
      RESULTS: In the BALF of the sensitized animals, as compared to the controls,
      there was a statistically significant increase in the percentage and absolute
      count of T-lymphocytes, CD4+ and CD8+. The CD4 / CD8 ratio in both groups did not
      differ significantly and was individually variable (2.94I0.72 SEM in the
      experimental group, vs 4.41I1.29 SEM in the control group). CONCLUSIONS: Both
      CD4+ and CD8+ lymphocytes (with some predominance of helper cells) participate in
      the efferent phase of the delayed type hypersensitivity reaction in the lung
      induced by antigen inhalation.

PMID- 11535925
TI  - Alteration of DNA base excision repair enzymes hMYH and hOGG1 in hydrogen
      peroxide resistant transformed human breast cells.
AB  - BACKGROUND: Oxidative stress is a major causative agent of carcinogenesis, aging,
      and a number of diseases. 8-oxoG is the most stable and deleterious lesion of
      oxidative DNA damage. The 8-oxoG lesions can be eliminated by human repair
      systems consisting of three enzymes hMTH1, hOGG1, and hMYH homologous to E. coli
      MutT, MutM, and MutY proteins, respectively. MATERIAL AND METHODS: Human cells
      (P1, P2, and P3) resistant to H(2)O(2) were derived from the non-tumorigenic
      human breast cell line MCF10A by sequential treatment of the cells with H(2)O(2).
      The protein expression levels of DNA repair enzymes were analyzed by Western
      blotting. The DNA binding and glycosylase activities of hMYH and hOGG1 were
      measured in the extracts of the H(2)O(2) resistant cells. RESULTS: The H(2)O(2)
      resistant cells displayed tremendously greater anchorage-independent growth
      capability and higher expression of the anti-apoptotic protein BCL-2 than the
      parental cells. H(2)O(2) detoxification ability was elevated in P1 and P2 cells,
      but not in P3 cells, suggesting P3 cells might employ a different defense
      mechanism from P1 and P2 cells. In P3 cells, both hOGG1 and hMYH glycosylase
      activities were reduced but their protein levels increased. Two A/8-oxoG binding
      complexes were detected with cell extracts: the fast-migrating complex (bottom
      form) was dominated in MCF10A cells, and was greatly reduced in P3 cells.
      Interesting, the P3 cells showing the least amount of bottom form had the weakest
      hMYH glycosylase activity. CONCLUSIONS: Our results demonstrated, for the first
      time, that alteration of base excision repair pathways is correlated to cell
      resistance to oxidative stress.

PMID- 11535926
TI  - Intestinal protection by lafutidine, a histamine H(2)-receptor antagonist,
      against indomethacin-induced damage in rats--role of endogenous nitric oxide.
AB  - BACKGROUND: We previously reported that lafutidine ((I)-2-(furfurylsulfinyl)-N-[4
      [4-(piperidinomethyl)-2-pyridyl]oxy-(Z)-2-butenyl] acetamide), a novel histamine
      H(2)-receptor antagonist, protects the small intestine against indomethacin
      induced damage, mediated by capsaicin-sensitive afferent neurons (CSN). MATERIAL
      AND METHODS: In the present study, we investigated whether or not the protective
      action of lafutidine against indomethacin-induced intestinal damage is mediated
      by endogenous nitric oxide (NO). Male SD rats were given indomethacin (10 mg/kg,
      s.c), killed 24 hr later, and the small intestinal mucosa was examined.
      Lafutidine (10 mg/kg) and capsaicin (10 mg/kg) was given p.o. twice 0.5 hr before
      and 9 hr after indomethacin. The NO synthase inhibitor N(G)-nitro-L-arginine
      methyl ester (L-NAME: 10 mg/kg) or the selective iNOS inhibitor aminoguanidine
      (10 mg/kg) was given s.c. 1 hr before lafutidine, while L-arginine (200 mg/kg)
      was given i.p. 10 min before L-NAME. RESULTS: Indomethacin produced severe
      lesions in the small intestine, accompanied by increases in enterobacterial
      translocation in the mucosa. Both lafutidine and capsaicin significantly reduced
      the severity of these lesions, together with suppression of bacterial
      translocation. The protective action of lafutidine as well as capsaicin was
      almost totally abolished by L-NAME but not aminoguanidine, in a L-arginine
      sensitive manner. Both lafutidine and capsaicin significantly increased
      intestinal mucus secretion, and these effects were also attenuated by prior
      administration of L-NAME. The exogenous NO donor NOR-3 prevented indomethacin
      induced intestinal lesions at the dose that stimulated the mucus secretion and
      inhibited the bacterial translocation. CONCLUSIONS: These results suggest that
      lafutidine protects the small intestine against indomethacin-induced damage, the
      action being dependent on CSN and mediated by endogenous NO produced by cNOS. The
      protective action of lafutidine may be attributable to suppression of the
      bacterial translocation following indomethacin, probably due to stimulation of
      intestinal mucus secretion.

PMID- 11535928
TI  - The activity of protein tyrosine kinases of rat heart after ischemia and
      reperfusion.
AB  - BACKGROUND: Protein phosphorylation plays a very important role in the modulation
      of signal transduction in many tissues including heart. The activities of protein
      tyrosine kinases (PTKs) of the heart are rather low but PTKs in cardiac myocytes
      could be involved in many processes including necrosis, apoptosis, and
      inflammation. All of them lead to heart failure and are the result of such
      conditions as ischemia and reperfusion. The aim of our study was to investigate
      if the ischemia and reperfusion could change the protein tyrosine kinases
      activities in rat cardiac myocytes. MATERIAL AND METHODS: The specific activities
      of PTKs were defined as (3)2P incorporation into exogenous poly(Glu, Tyr)--known
      as an artificial substrate for all types of protein tyrosine kinases. RESULTS:
      The activity of tyrosine kinases in ischemic heart was lower than in control
      intact heart and amounted to 50-60% of control values. In the heart after
      ischemia and following reperfusion the activities of PTKs increased to 135% of
      control. CONCLUSIONS: Ischemia and reperfusion changed activity of PTKs. There
      were no differences in protein tyrosine activity between the left and right
      ventricles.

PMID- 11535929
TI  - The peripheral blood lymphocyte pattern in psoriasis preceded by an infection.
AB  - BACKGROUND: There is a great deal of information to suggest that activated T
      cells play a major role in the pathogenesis of psoriasis. Less is known about the
      possible influence of a trigger bacterial antigen on circulating blood cells. The
      purpose of our study was to analyze the quantity and subpopulations of activated
      lymphocytes in peripheral blood in patients with psoriasis preceded by an
      infection and in a control group. MATERIAL AND METHODS: Thirty-two patients with
      psoriasis induced by an infection and twenty-two healthy controls were examined.
      The T lymphocytes in peripheral blood were examined by means of flow cytometry,
      using panels of monoclonal antibodies. Expression was estimated by reference to
      the fluorescence intensity of the surface antigens studied. RESULTS: A decreased
      percentage of CD3+, CD4+, and CD4+-bearing IL-6 receptor cells, a decreased
      expression of CD3, CD19, and CD4 antigens, and a significantly increased
      percentage of CD45RO+CD4+ were found in the studied subpopulation of lymphocytes.
      CONCLUSIONS: Our research demonstrated changes in the percentage and expression
      of certain subpopulations of T lymphocytes in peripheral blood in the course of
      psoriasis preceded by a bacterial infection, which suggests not only local, but
      also systemic activation of the immune system.

PMID- 11535930
TI  - Composition of free fatty acid and triglyceride fractions in human necrotic
      pancreatic tissue.
AB  - BACKGROUND: Lipolytic enzymes, such as lipase, phospholipase A(2), lipoprotein
      lipase, and hormone-sensitive adipocyte lipase are probably implicated in the
      pathogenesis of acute pancreatitis. The increased activity of these enzymes can
      cause specific changes in fatty acid composition, both to free fatty acid (FFA)
      and triglyceride (TG) fractions in necrotically changed pancreatic tissue.
      MATERIAL AND METHODS: Specimens of necrotically changed pancreatic tissue taken
      intraoperatively from 13 patients operated for serious necrotic acute
      pancreatitis were analysed. The Folsch extraction method and separation of lipids
      by thin-layer chromatography was used, and the final fatty acid composition was
      determined after methylation by gas liquid chromatography. RESULTS: The changes
      in the FFA fraction are more definite than those for the triglyceride fraction
      and refer mostly to the increased percentage distribution of unsaturated fatty
      acids. CONCLUSIONS: These studies lead to the hypothesis that fatty acids
      released in the process of lipolysis play a key role in the pathogenesis of acute
      pancreatitis.

PMID- 11535931
TI  - Stentless valved composite graft for replacement of the aortic valve and
      ascending aorta.
AB  - BACKGROUND: Conduits with biological valves are rarely used for aortic root
      replacement because of technical problems when degeneration of the valve
      prosthesis requires reoperation. A composite graft as described could likely
      avoid this problem. MATERIAL AND METHODS: Between November 1998 and November
      1999, 28 consecutive patients underwent replacement of the ascending aorta and
      aortic valve with a stentless valved composite graft. The indication for surgery
      was aneurysm of the ascending aorta (26 patients) and aortic dissection (2
      patients). The composite graft was assembled during surgery using a stentless
      porcine aortic bioprosthesis (Toronto SPV) and a woven polyester collagen-coated
      vascular prosthesis (InterGard). RESULTS: There was no hospital mortality.
      Echocardiographic evaluation before discharge showed excellent hemodynamics with
      a mean transvalvular gradient of 8.5 mmHg (standard deviation I3.0 mmHg) and no
      regurgitation across the valve. Within a follow-up period of up to one year there
      was one late death because of a cerebral hemorrhage under anticoagulation.
      CONCLUSIONS: The valved composite graft described offers the excellent
      hemodynamic performance of a stentless biological valve and is expected to avoid
      major technical difficulties should later replacement of the biological
      prosthesis due to structural failure become necessary, because only the valve
      cusps need to be resected, leaving the tube graft untouched.

PMID- 11535932
TI  - Correlation between left ventricular mass and the resting and post-exercise
      release of ANP in healthy men.
AB  - BACKGROUND: The goal of our study was to assess the impact of left ventricular
      mass on the resting and post-exercise release of atrial natriuretic peptide (ANP)
      in healthy young men. MATERIAL AND METHODS: The study involved 36 young men
      divided into two groups. Group I consisted of 18 healthy untrained men 20-24
      years old (mean 22.1). Group II included 18 healthy men aged 22-27 years (mean
      23.4 years) who had been taking regular dynamic and static physical exercise for
      at least 2 years. Echocardiograms were performed in both groups. The thickness of
      the posterior wall (PW-d), the thickness of the interventricular septum (IV-d),
      and the left ventricular end-diastole dimension (DdLV) were measured and used to
      calculate the left ventricular mass. Subsequently, all the patients underwent an
      exercise test on a cycloergometer. The workload in both groups was 2 Watts/kg at
      60 rpm. The anticipated age-adjusted heart rate values at this workload were
      170/min in Group I and 155/min in Group II. Blood samples were collected before
      the exercise test and 1 minute afterwards. The concentrations of ANP and sodium
      ions and the hematocrit index were measured. RESULTS: In Group I the mean left
      ventricular mass was 193.1 +/- 51.8 g; in Group II, 248.1 x 91.91 g, which is a
      statistically significant difference. The resting ANP concentration in Group I
      was higher than in Group II (24.44 +/- 12.35 pg/ml vs 21.39 +/- 11.03 pg/ml), but
      the difference was not statistically significant. After exercise there was a
      significant increase in ANP concentration in both groups: 53.89 +/- 39.98 pg/ml
      and 47.50 +/- 26.67 pg/ml respectively. There was no correlation between the ANP
      concentration before and after exercise and the left ventricular mass in either
      group. There were also no differences between the two groups in resting
      hematocrit: 48% in Group I and 49.5% in Group II. A significant increase in
      hematocrit was observed in both groups after exercise. Exertion induced a
      significant decrease in the plasma sodium concentration in both groups. The ratio
      of mean plasma ANP concentration at rest to left ventricular mass, corrected
      according to hematocrit values, was 6.10 in Group I and 4.25 in Group II; after
      exercise, 14.06 and 9.72 respectively. The ratio of post-exercise increase in ANP
      concentration to left ventricular mass was 7.6 in Group I and 5.32 in Group II.
      The average left ventricular mass in Group II, although 30% greater than in Group
      I, did not exceed 259 g, which is considered the upper limit of normal. Despite
      this difference the ANP concentration in Group II was ca. 20% lower than in Group
      II, without cardiac hypertrophy. In both groups a significant increase in ANP
      concentration was observed when the subjects were exposed to submaximal workload.
      In Group II, however, the increase was markedly lower. No correlation was found
      between left ventricular mass at rest and post-exercise ANP release, nor between
      left ventricular mass and ANP secretion. By contrast, a tendency towards lower
      ANP release was found in Group II, despite the markedly larger left ventricular
      mass. CONCLUSIONS: In the evaluation of risk related to left ventricular
      hypertrophy, both the mass index and cardiac functional efficiency should be
      taken into account.

PMID- 11535933
TI  - Analysis of the expression of estrogen and progesteron receptors, and of PCNA and
      Ki67 proliferation antigens, in uterine myomata cells in relation to the phase of
      the menstrual cycle.
AB  - BACKGROUND: The purpose of this study was to provide an immunocytochemical
      evaluation of the expression of receptors for estrogens (ER) and progesterone
      (PgR), and of Ki67 and PCNA (proliferating cell nuclear antigen) proliferation
      antigens in uterine myomata cells in three groups of patients operated in various
      phases of the menstrual cycle, and to determine the relationship between the
      expression of the receptors, the proliferative activity of myoma cells, and the
      phase of the menstrual cycle during which the tumor was excised. MATERIAL AND
      METHODS: The studies were performed on samples of uterine 85 leiomyomata. Twelve
      of the patients were operated in the follicular phase of menstrual cycle, 50 in
      the luteal phase, and 27 in the post-menopausal period. The receptors and
      proliferating antigens were detected immunocytochemically. The intensity of the
      immunocytochemical reaction was evaluated using the ImmunoReactive Score (IRS).
      RESULTS: In all three groups of patients the expression of PgR significantly
      exceeded that of ER. Also, in all the patients the mean expression of PCNA
      significantly exceeded the expression of Ki76. CONCLUSIONS: The expression of the
      studied antigens did not depend upon the phase of the menstrual cycle, and was
      similar in the postmenopausal period.

PMID- 11535934
TI  - IL-6 and sIL-6R concentration in the cerebrospinal fluid and serum of MS
      patients.
AB  - BACKGROUND: The aim of this study was to determine the concentration of cytokine
      IL-6 in correlation with its soluble receptor sIL-6R in the serum and CSF of MS
      patients. MATERIAL AND METHODS: The study group consisted of 52 MS patients in
      clinical stage 2-7 according to the Kurtzke Scale (mean 3.6 +/- 1.8); the disease
      duration ranged from 2 to 22 years. The levels of interleukin-6 and sIL-6R in
      serum and CSF were determined using commercial ELISA kits. RESULTS: An
      significant increase of IL-6 (p=0.03) was found in the serum of MS patients (12.1
      +/- 1.8 pg/ml) in comparison to the control group (6.6 +/- 4.5 pg/ml). The
      concentration of IL-6 in the CSF of MS patients was 13.4 +/- 1.77 pg/ml, and in
      the majority of patients was higher than in the serum. The highest mean IL-6
      concentrations in serum and CSF were found in patients with a longer disease
      duration, although the differences were not statistically significant. We found
      some degree of dependence between the serum IL-6 concentration and the level of
      disability on the Kurtzke scale. The concentrations of sIL-6R in serum (34.0 +/-
      39.0 pg/ml) and cerebrospinal fluid (1.4 +/- 3.3 pg/ml) were significantly higher
      in MS patients than in the controls. CONCLUSIONS: IL-6 and its soluble receptors
      are involved in a complex immunological reaction that is characteristic for MS.
      However, the significant differences in the results obtained here from those
      reported in other studies make it rather unlikely that IL-6 and its receptors
      could be used as surrogate markers of MS activity.

PMID- 11535935
TI  - Changes in insulin-like growth factor I, 17-b-estradiol, and progesterone in
      postmenopausal women with benign and malignant ovarian tumours.
AB  - BACKGROUND: The aim of this research was to observe changes in IGF-I and steroid
      hormones in postmenopausal women with benign and malignant ovarian tumors.
      MATERIAL AND METHODS: The concentrations of insulin-like growth factor I (IGF-I),
      17-b-estradiol and progesterone were examined by radioimmunological assay in
      three groups of postmenopausal women: patients with malignant ovarian tumors,
      patients with benign ovarian tumors, and healthy women. In all three groups the
      age and body mass index (BMI) were comparable. RESULTS: The concentrations of IGF
      I in the serum of the patients with malignant cancer were significantly lower.
      The concentrations of estradiol were significantly higher in the patients with
      both benign and malignant ovarian tumors as compared to the controls.
      CONCLUSIONS: Decreased IGF-I concentration in the serum of postmenopausal women
      with ovarian tumors may suggest that the tumor is malignant.

PMID- 11535936
TI  - Evaluation of interleukin concentrations in amniotic fluid in preterm and term
      parturition and in oligohydramnios.
AB  - BACKGROUND: The goal of our work was to evaluate the activity of interleukin 1
      beta, 6, 8, 12, and 18 in the amniotic fluid in preterm and term deliveries, and
      to specify the dependency between the amniotic fluid index (AFI) and the
      concentration of these interleukins. MATERIAL AND METHODS: Amniotic fluid (27
      samples from preterm deliveries and 49 from term deliveries) was collected during
      cesarean section or in the course of amnioinfusion performed when the pregnancy
      was accompanied by oligohydramnios (AFI< or = 5cm). The amniotic fluid thus
      obtained was centrifuged at 1000 xg for 15 min. at a temperature of 4 degrees C,
      and the filtrate was kept at a temperature of -80 degrees C until assayed. The
      assays were done by the ELISA method, using ready antibody kits from 'R&D
      Systems'. A comparative analysis was done for the concentrations (expressed in
      pg/ml) of the individual interleukins found in the amniotic fluid from preterm
      and term deliveries, and for the amniotic fluid index (AFI< or = L5 and >5). The
      statistical analysis was performed using the Wilcoxon test. RESULTS: The
      increased level of IL-12 we found in the amniotic fluid from preterm deliveries
      and those complicated by oligohydramnios may indicate the participation of
      immunological mechanisms in the pathogenesis of oligohydramnios.

PMID- 11535937
TI  - The concentration of galanin in postmenopausal women before and after application
      of hormone replacement therapy compared to women of reproductive age.
AB  - BACKGROUND: Hormone replacement therapy (HRT) during menopause exerts an
      essential impact on neuroendocrine regulation within the hypothalamic-pituitary
      system. The sex steroids, especially estrogens, are responsible for the synthesis
      and secretion of neuropeptides and neurotransmitters, such as galanin,
      neuropeptide Y, the opioid peptides, dopamine, serotonin, and others. The purpose
      of our research was to evaluate the concentration of galanin in postmenopausal
      women before and after the application of HRT, and to compare these values to the
      concentrations found in women of reproductive age. MATERIAL AND METHODS: The
      experimental group consisted of 20 women (average age 53 +/- 5.2). The average
      time elapsed since the last menstruation in these women was 5.3 year I 1.4.
      RESULTS: The differences in the concentrations of galanin before (8.24 +/- 3.62
      pg/ml) and after (5.63 +/- 2.75) the application of HRT were not statistically
      significant. These values were significantly lower, however (p<0.05), than the
      galanin concentrations in women of reproductive age (22.03 +/- 12.02 pg/ml). The
      concentrations of estradiol prior to the administration of HRT (0.021 +/- 0.02
      ng/ml) were significantly lower (p.<0.001) than after the application of hormone
      replacement therapy (0.09 +/- 0.156 ng/ml). The concentrations of estradiol in
      the control group averaged 0.070 +/- 0.04 ng/ml, significantly higher than in the
      group of post-menopausal women given HRT (p.<0.05). No statistically significant
      difference was found between the galanin concentration in women of reproductive
      age and in postmenopausal women using HRT. CONCLUSIONS: Our research results
      indicate that serum galanin in postmenopausal women is significantly lower than
      in women of reproductive age. The application of hormone replacement therapy does
      not restore galanin concentrations to levels typical for women of reproductive
      age.

PMID- 11535938
TI  - Red cell deformability in patients with chronic atheromatous ischemia of the
      legs.
AB  - BACKGROUND: It has been shown that atherosclerosis can cause not only lowering of
      the perfusion pressure gradient at the macro/micro circulation level, but can
      bring about untoward rheological changes such as e.g. loss of the red blood cells
      (RBC) elasticity. This can participitate in mechanism of impairment of the blood
      flow through the microcirculation as well. The aim of this study was to measure
      RBC elasticity in the claudicants, and to evaluate the effect of the applied
      treatment either conservative or surgical revascularisation on this rheological
      parameter. MATERIAL AND METHODS: RBC deformability was examined in claudicants 83
      of them (mean claudication distance 400 m) were treated conservatively (walking
      exercise on a treadmill and Pentoxyphilline 600 mg b.i.d.) 44 claudicants with
      the critical leg ischemia (mean claudication distance below 50 m or rest pain)
      underwent surgical revascularisation. The measurements of RBC elongation (under
      selected values of the shear stress) were made on entry to the study, after 6
      weeks, and 12 weeks of observation. RESULTS: After 12 weeks of conservative
      treatment, RBC elasticity both at rest and after walking exercise significantly
      increased. In the patients undergoing surgery mean RBC elasticity both at rest
      and after walking exercise 12 weeks following surgery was not significantly
      different compare with the respective levels at the beginning of the study.
      CONCLUSIONS: In the group of claudicants with less advanced atherosclerosis
      (conservative group), the treatment brought about significant increase of RBC
      elasticity. On the contrary in case of the patients with advanced atherosclerosis
      and critical leg ischemia revascularisation alone appeared to be ineffective in
      correction of untoward rheologic alteration such as rigidity of the erythrocytes.

PMID- 11535940
TI  - Diurnal profile of melatonin secretion in the acute phase of major depression and
      in remission.
AB  - BACKGROUND: The aim of this study was to determine whether there are differences
      in the 24-hour melatonin secretion profile between patients with major depression
      (MD) before and after clomipramine treatment, and a control group, and also
      whether or not there exist statistically significant differences in the melatonin
      levels depending on the severity of depression. MATERIAL AND METHODS: 20 patients
      with MD and 14 healthy volunteers took part in the study. Before and after
      clomipramine treatment all the patients had an 8 ml blood sample collected 7
      times, at fixed hours, for measurement of the melatonin level. The severity of
      depression was assessed (HAMDS, BDI, POMS) before and after treatment. RESULTS:
      The mean melatonin concentration at each of the chosen hours was higher in
      persons with MD than in the control, but the differences reached statistical
      significance only at certain night hours. In both groups the nocturnal rise in
      melatonin secretion began at 12 midnight, reaching its peak at 2 am, to reach low
      values by 8 am, similar to the values from the previous morning. After 8 weeks of
      clomipramine treatment, the melatonin concentrations at 12 midnight, 2 am, and 4
      am were lowered, and were elevated at 8 am, 2 pm, and 8 pm. The difference was
      statistically significant only at 8 pm. Melatonin secretion during both night
      time hours and daytime hours is higher in individuals with MD than in healthy
      subjects, and remains elevated after 8 weeks of effective clomipramine treatment.
      Those patients whose state changed the least after 8 weeks of clomipramine
      treatment differed in a statistically significant way in terms of melatonin
      secretion level at 2 pm from those patients who improved the most. CONCLUSIONS:
      Some patients with MD have elevated melatonin concentration levels during daytime
      and nighttime hours, and this melatonin secretion pattern is independent of the
      severity of depression.

PMID- 11535939
TI  - The activity of cholesterol esterase and ceruloplasmin are inversely related in
      the serum of men with atherosclerosis obliterans.
AB  - BACKGROUND: Ceruloplasmin is a copper-containing (2-glycoprotein and a member of
      the acute phase reactant family. Parallel changes in ceruloplasmin and copper
      concentration have been observed in diseases accompanied by severe inflammation,
      indicating a closely related process. Cholesterol esterase participates in
      lipoprotein degradation by the hydrolysis of cholesteryl esters in low density
      lipoproteins (LDL-CE). LDL-CEs are substrates for cholesterol esterase, but can
      also undergo oxidation by metal ions. The reduction of lipid hydroperoxides has
      been claimed to play a key role in the control of lipid peroxidation in living
      systems. MATERIAL AND METHODS: The experimental group consisted of 16 men with
      atherosclerosis obliterans of the lower limbs, with 12 healthy male volunteers as
      a control group. The activity of cholesterol esterase (CEase), ceruloplasmin
      (Cp), and glutathione peroxidase (GPx), and the concentrations of
      malonyldialdehyde (MDA) and copper were determined in serum samples. RESULTS:
      CEase and Cp activity and copper concentrations were found to be greater in the
      AO group than in the controls. In addition, CEase and Cp were negatively
      correlated (r=(0.65, p< or = 0.05) in the serum of men with AO, but not in the
      controls. Moreover, copper concentration was significantly correlated with the
      activity of Cp and GPx (r=0.81 and r=0.58, respectively). The reduced GPx
      activity and the higher MDA concentration found in the AO group indicate a
      decline in the antioxidative barrier of plasma. CONCLUSIONS: The results reported
      here show an inverse relationship between the activities of CEase and Cp in
      chronic arterial occlusion of the lower limbs, which may reveal the interaction
      between the antioxidant and lipolytic enzymes.

PMID- 11535941
TI  - Psychosomatic reactions to a stressful environment and an attempt at
      pharmacological modification.
AB  - BACKGROUND: Extreme environmental conditions significantly influence the
      functioning of the human organism and trigger distinct stress reactions. In our
      study we attempted to create an experimental model of complex stress conditions.
      MATERIAL AND METHODS: Healthy male volunteers were isolated, deprived of food and
      sleep, and exposed to extreme temperatures for 5 consecutive days. Physical
      fitness and selected somatic parameters and biochemical stress markers were
      measured in the tested subjects. In addition, changes in behavior and mental
      status were assessed by means of a set of psychological tests. Finally, the
      effects of pharmacological modification (administration of clobazam and tramadol)
      on psychosomatic stress reactions were tested. CONCLUSIONS: The results indicate
      that our experimental stress conditions slightly altered the mental functions of
      the subjects, increased their anxiety level, hampered their physical efficiency,
      and led to weight loss. The administration of the drugs beneficially influenced
      the subjects' memory and physical efficiency.

PMID- 11535942
TI  - Serum iron parameters in patients with alcoholic and chronic cirrhosis and
      hepatitis.
AB  - BACKGROUND: The aim of our study was to asses the serum iron status of patients
      with various forms of hepatitis and cirrhosis of the liver and to determine the
      correlation between the degree of hepatocyte damage and the status of serum iron
      parameters. MATERIAL AND METHODS: The study involved 136 subjects with chronic
      viral hepatitis type C (group I, n=71) and type B (group II, n=29), alcoholic
      cirrhosis of the liver (group III, n=15), postinflammatory cirrhosis of the liver
      (group IV, n=13), and alcoholic hepatitis (group V, n=8). In all these patients,
      serum alanine (ALT) and aspartate (AST) aminotransferase activity were used as a
      secondary measure of necroinflammatory activity. The serum iron status
      measurements included iron concentration (Fe), total iron-binding capacity
      (TIBC), transferrin saturation, and ferritin concentration. RESULTS: Our study
      results led us to conclude that the mean value of serum iron concentration did
      not differ significantly among the analysed groups (p>0.05). The transferrin
      value - estimated as the total iron-binding capacity (TIBC) - was significantly
      lower in alcoholic cirrhosis of the liver in comparison to both chronic hepatitis
      C (p<0.004) and chronic hepatitis B (p<0.04). The transferrin saturation was
      statistically the higher in group III in comparison with both group I (p<0.0031)
      and group II (p<0.024). Serum ferritin was significantly higher in cirrhotic
      patients regardless of etiology, in comparison with patients with chronic viral
      hepatitis (p<0.045). We found correlation between an increase of both AST and ALT
      and a higher level of ferritin in patients with chronic hepatitis type C
      (p<0.005, p<0.02) and type B (p<0.05, p<0.03) and alcoholic hepatitis (p<0.05).
      CONCLUSIONS: In the course of chronic liver diseases we may observe slight
      irregularities in iron status relating to both the serum and store pool of this
      element. The most significant disturbances are seen in patients with alcoholic
      cirrhosis of the liver.

PMID- 11535943
TI  - Positive family history of allergy in children with hypersensitivity to cow's
      milk.
AB  - BACKGROUND: Allergy belongs to the most frequent chronic diseases in developed
      countries. Its manifestation and development are determined by genetic
      predisposition as well as specific and non-specific environmental factors. The
      aim of this paper was to evaluate the type and incidence of allergic/atopic
      diseases among family members (1st and 2nd degree of kinship) of children with
      the diagnosis of hypersensitivity to cow's milk. MATERIAL AND METHODS: Positive
      family history of atopic and allergic diseases among the closest relatives was
      analysed in a group of 180 children with the diagnosis of hypersensitivity to
      cow's milk. RESULTS: Allergoses were found in 163 (91.1%) families, affecting
      55.5%, 36% and 50% mothers, fathers and siblings of the patients, respectively.
      The disease of the same type as in children was present in 37.2% siblings and in
      11.7% parents. Forty-five per cent of patients were from high-risk families,
      where 2, 3 or 4 relatives were affected by the disease (in 37.8%, 6.7% and 0.56%
      cases, respectively). CONCLUSIONS: Clinical manifestation of allergoses differed
      between various generations of the same family. The systems most often affected
      by the allergic process were skin, gastrointestinal tract and respiratory system.

PMID- 11535944
TI  - The frequency of occurrence and clinical picture of celiac disease in the parents
      of children with the disease.
AB  - BACKGROUND: In view of the considerable changes that have taken place in the last
      20 years in the clinical picture of celiac disease, epidemiological research is
      now underway to search for atypical forms, which are appearing with growing
      frequency; if not treated, they cause a deterioration in the quality of life of
      these patients. The goal of our research was to identify the frequency of
      occurrence of celiac disease among the parents of children with the disease and
      to analyze the clinical picture in these cases. MATERIAL AND METHODS: The
      research involved 254 persons (127 women, 127 men) ranging in age from 25 to 58
      years. The subjects were pairs of parents of randomly selected children with
      celiac disease diagnosed in accordance with the ESPGHAN criteria in force at the
      time of diagnosis. The level of total IgA and antiendomysial antibodies in class
      IgA or IgG were measured in all subjects using the indirect immunofluorescence
      method. In all those patients with a positive test for the presence of IgAEmA who
      expressed their consent, a biopsy of the small intenstine was performed, with a
      histopathological evaluation of the bioptate according to the Shmerling Scale.
      RESULTS: The IgA level was normal in all subjects. The presence of IgAEmA was
      indicated in the serum of 5 subjects (2%): 3 men aged 39, 40 and 43, 2 women aged
      41 and 43. The level of IgAEmA varied within the limits of +20 to +640 IF. In 4
      of these subjects an endoscopic biopsy of the small intestine was performed,
      providing a basis for the diagnosis of level III/IV or level IV atrophy of the
      intestinal villi. The clinical symptoms found in the subjects prior to diagnosis
      were diverse: periodic loose stools (2 persons), short stature (3 men), abdominal
      pains (3 persons with concomitant inflammatory lesions in the stomach membrane or
      duodenum), sudden loss of body mass (1 case), hyperexcitability (1 case). One
      female subject did not report any significant complaints. CONCLUSIONS: Screening
      tests should be performed In the families of patients with celiac disease in the
      direction of enteropathy, even in a case when clinical symptoms are absent, weak,
      or atypical.

PMID- 11535945
TI  - Specific humoral immunity in mumps meningitis in children.
AB  - BACKGROUND: The pathogenesis of mumps meningitis remains unclear. The aim of this
      study was to assess the relation between IgM and IgG levels in blood and their
      relationship with the picture of CSF. MATERIAL AND METHODS: We tested 40 children
      of both sexes aged 2-14 years. CSF was examined at admission (I) and after 12-14
      days (II). Antibodies were measured four times: at admission (I), and after 2
      (II), 4 (III), and 8 weeks (IV) by EIA (Behring). The results were expressed as
      delta absorbency. RESULTS: The mean IgM level was respectively 0.403; 0.424;
      0.317; 0.220. Significant differences were demonstrated between tests I and III
      and between III and IV. The mean IgG level was respectively 0.923; 1.322; 1.381
      and 1.257. Significant differences were noted between tests I and II and between
      III and IV. We observed significant positive correlations between the IgM levels
      in tests I and II, II and III, and III and IV. The IgG concentrations
      significantly correlated in tests I and II, II and III, and II and IV.
      Significant negative correlations were noted between the IgG levels at test I and
      the IgM levels at test II. A negative correlation also appeared between the IgM
      level and CFS pleocytosis at admission, and between the IgM concentration and CSF
      pleocytosis after two weeks. A positive correlation was found between the IgG
      level at test I and the CSF glucose level in test II. In this study a high IgG
      level probably resulted in a lower IgM level at the next test. The IgM
      concentration at week 8 weeks was about 50% lower than its highest concentration
      (week 2), while the IgG level decreased simultaneously. The IgM concentration at
      hospital admission and two weeks later influenced CSF pleocytosis during these
      periods (higher IgM level - lower pleocytosis). A high IgG level at admission
      resulted in a lower CSF glucose concentration at the second examination.

PMID- 11535946
TI  - Fungal colonization of gastric mucosa and its clinical relevance.
AB  - BACKGROUND: The aim of our study was to evaluate the incidence of fungi in the
      stomach in patients with gastric ulcer and chronic gastritis in comparison to
      healthy humans, and to identify the fungus species isolated from these patients
      and their susceptibility to antifungal agents. We also assessed the coincidence
      of the presence of antifungal antibodies and fungal mannan antigen in serum with
      the concentration of fungi in the stomach. MATERIAL AND METHODS: We investigated
      293 patients, aged 20-80, who visited the Gastroenterology Outpatient Clinic at
      the Jagellonian University's Collegium Medicum in Cracow, complaining of
      dyspeptic symptoms or clinical manifestations of ulcer disease. The examinations
      included endoscopy of the upper part of the alimentary tract with sampling of
      gastric contents, as well as surface brushing and biopsy from the bottom of the
      ulceration for mycological analysis. Also, biopsy specimens from the margin of
      the ulceration or inflammatory mucosa were collected for histological examination
      and urease testing. RESULTS: Gastric mucosa and stomach contents are often an
      area of fungal colonization, which was detected in 54.2% of the gastric ulcer
      cases and 10.3% of the chronic gastritis cases. The most frequently isolated
      fungus species was Candida albicans, although other fungi, previously considered
      rare or uncommon, were also found. A difference in growth in vitro between the C.
      albicans, C. tropicalis and C. lusitaniae strains was discovered: C. albicans and
      C. tropicalis grew from pH 2.0, while C. lusitaniae grew from pH 3.0. This
      finding suggests differentiation in the properties of these fungi. CONCLUSIONS:
      The lack of correlation between the concentration of fungi, the titre of
      antifungal antibodies and the presence of fungal antigen in serum suggests that
      fungal colonization is secondary in nature.

PMID- 11535947
TI  - The prognostic significance of microalbuminuria in non-diabetic acute stroke
      patients.
AB  - BACKGROUND: Microalbuminuria (MA) is thought to be a marker of widespread
      vascular damage. It is associated with increased mortality in diabetes mellitus,
      hypertension and acute myocardial infarction. The aim of the present study was to
      evaluate the prognostic significance of MA in non-diabetic acute stroke patients.
      MATERIAL AND METHODS: We studied 52 patients (mean age 69.3 +/- 12.5 years)
      diagnosed with ischemic stroke confirmed by computed tomography, who were
      admitted to the Stroke Unit within 24 hours after the onset of symptoms. The
      control group consisted of 37 age- and gender-matched subjects (mean age 65.2 +/-
      5.7 years), examined 3 to 18 months after ischemic stroke. We excluded patients
      with diabetes mellitus, positive urinalysis, proteinuria, hepatic or renal
      insufficiency, neoplastic disease or clinical signs of infection. The severity of
      the neurological deficit was assessed by the Scandinavian Stroke Scale (SSS). The
      albumin excretion rate was measured in daily urine collection on the second day
      of hospitalization, using the immunonephelometric method. The patients were
      followed up for three months. RESULTS: MA was found in 24 of 52 (46.1%) acute
      stroke patients and in 5 of 37 (13.5%) controls (p<0.05). Patients with MA scored
      lower on the SSS than patients without MA, both on admission and later. We found
      a correlation between the daily excretion of albumin and the severity of
      neurological deficit on admission, as expressed by the SSS score (r = -0.48,
      p<0.05). The 90-day mortality rate was higher in patients with MA as compared to
      patients without MA (45.8% vs 7.1%). Patients with MA scored lower on the Barthel
      Index on Day 90 (median: 65 vs 100, p<0.01). CONCLUSIONS: We found that MA can be
      detected in about 46% of non-diabetic patients with acute ischemic stroke.
      Measuring the albumin excretion rate may be a reliable predictor of increased
      mortality 3 months after stroke.

PMID- 11535948
TI  - Incidence of Chlamydia pneumoniae infection in patients with coronary artery
      disease subjected to angioplasty or bypass surgery.
AB  - BACKGROUND: Seroepidemiological, pathological and animal studies suggest that
      chronic infection with Chlamydia pneumoniae (Cp) may directly impact the
      development or progression of atherosclerosis and coronary heart disease. The aim
      of the present study was to determine the seroprevalence of Cp infection and
      markers of systemic inflammation in patients undergoing routine coronary artery
      examination and prior to heart revascularization. MATERIAL AND METHODS: The
      research involved 76 patients with severe CAD and 81 control patients with normal
      coronary circulation confirmed by coronary angiography. The presence of serum IgG
      and IgA antibodies to Cp and plasma interleukin-8 (IL-8) levels was measured by
      EIA test. Furthermore, the levels of plasma C-reactive protein, fibrinogen, total
      cholesterol, and triglycerides were measured in all patients. RESULTS:
      Seropositivity to Cp was found in 60.5% for IgG and in 61.8% of cases for IgA
      with CAD patients, as compared to 26.0% and 29.5% in the controls (p<0.001),
      respectively. The levels of Interleukin-8, plasma fibrinogen, total cholesterol
      and triglycerides were significantly higher (p<0.001) in the CAD group, while C
      reactive protein tended to have a higher value in patients with atherosclerosis
      than in the control group, although the difference was not significant.
      CONCLUSIONS: Cp infection significantly increases the risk of CAD, usually
      requiring coronary bypass surgery or percutaneous coronary intervention as
      effective measures. It may also modify the levels of serum lipids, CRP and
      fibrinogen, increasing the risk of atherosclerosis. The strong correlation
      between the elevated IgG and IgA titers of Cp in patients treated with
      angioplasty or surgery may impact their follow-up; this issue requires further
      investigation.

PMID- 11535949
TI  - Daily selenium intake by breast-fed infants and the selenium concentration in the
      milk of lactating women in western Poland.
AB  - BACKGROUND: Human milk is the only natural source of food for infants during the
      first several months of life. The milk should contain all trace elements in
      adequate amounts, including selenium (Se). Se is of particular interest because
      the daily requirement for this element in infants is higher due to their rapid
      growth. The aim of our study was to determine the Se concentration in human milk
      and to calculate the daily Se intake by breast-fed infants in western Poland.
      MATERIAL AND METHODS: The Se concentration was assayed in mature human milk (14
      to 58 days after parturition) collected from 352 lactating women living in 7
      voivodeships in western Poland. The concentration of Se was measured by the
      fluorometric method with 2,3-diaminonaphthalene as a complexing reagent. The
      values were expressed as ng/ml. RESULTS: No significant differences were observed
      in terms of Se concentration among the milk samples collected from the different
      voivodeships. However, the highest values were obtained in the northern part of
      the region. The mean Se concentration was 10.51 +/- 2.76 ng/ml (range: 10.41
      10.65 ng/ml). The calculated mean daily Se intake by breast-fed infants was 7.71
      microg/day (range: 3.67-17.17 microg/day). CONCLUSIONS: The Se concentration in
      human milk in the region studied here is uniform, but the daily Se intake of
      breast-fed infants in the western part of Poland is lower than the recommended
      daily requirement. The reason for this situation would appear to be low Se
      content in the soil, and consequently in the foodstuffs from this region.

PMID- 11535950
TI  - Blood levels of selected hormones in patients with multiple sclerosis.
AB  - BACKGROUND: Hormonal studies in patients with multiple sclerosis are rare and
      they often produce results which are difficult to interpret. These
      investigations, however, are becoming more and more important as they may cast
      some light on possible interrelationships between hormonal and immune systems.
      The aim of the present work was to investigate endocrine function in patients
      with multiple sclerosis on the basis of blood levels of selected pituitary (TSH,
      ACTH, GH) and thyroid hormones (T3, T4), and cortisol. MATERIAL AND METHODS:
      Forty-nine MS subjects, including 25 menstruating women, 6 post-menopausal women
      and 18 men were included in the analysis. The hormones were measured by
      radioimmunoassay and immunoradiometric assay kids. RESULTS: Pituitary function in
      respect of TSH, corticotropin and growth hormone secretion was normal. Both men
      and women suffering from multiple sclerosis manifested low serum T3
      concentrations coexisting with normal T4 levels which may indicate changed
      peripheral conversion pathway of thyroid hormones. On the other hand, the
      disturbances in pituitary-adrenal cortex system in respect of glycocorticosteroid
      secretion were not observed. CONCLUSIONS: Normal function in respect to pituitary
      hormones (TSH, corticotropin, growth hormone) and normal T4 level versus low
      serum T3 concentration may indicate changes in peripheral conversion pathway of
      thyroid hormones in MS patients.

PMID- 11535951
TI  - Systemic sclerosis complicated by diffuse alveolar hemorrhage.
AB  - A 38-year-old woman with limited cutaneous systemic sclerosis and pulmonary
      fibrosis developed diffuse alveolar hemorrhage during the course of her disease
      that responded well to steroids. We present the clinical history of the patient
      and discuss the different theories behind the association. The importance of
      steroid therapy for treatment of alveolar hemorrhage in this particular condition
      is emphasized.

PMID- 11535952
TI  - A comparative study of cefaclor vs. amoxicillin/clavulanate in
      tonsillopharyngitis.
AB  - BACKGROUND: Acute pharyngotonsillitis (APT) is one of the most common
      inflammatory processes of adults and children in an outpatient setting.
      Increasing failure rates, hypersensitivity to penicillin, the required multiple
      daily doses and common side effects lead to poor patients compliance and thus
      inadequate treatment duration, providing therefore ground for considering
      alternative antimicrobial agents. MATERIAL AND METHODS: This multicenter,
      randomized, single blind study was undertaken in order to compare efficacy and
      safety of cefaclor (375 mg BID) and amoxicillin/clavulanate (625 mg BID) in 10
      days treatment regiment of ambulatory patients with APT. A total of 200 patients
      (age range between 12-65 years) with symptoms of APT and positive antigen strep
      test were enrolled into the study. Clinical and bacteriological responses were
      assessed after the end of treatment (14th-18th day) and at the follow-up visit
      (38th-45th day). All GABHS strains, isolated from throat cultures, were tested
      for in vitro sensitivity to the antibiotics used in the study and no strain was
      found resistant to both antibiotics. RESULTS: The results indicated that both
      antibiotics had high--almost 99% effectiveness at the post therapy visit. On the
      follow up visit an increased tendency of relapses was observed in the
      amoxicillin/clavulanate treated group, compared to cefaclor treated group (8.33%
      vs 3.29%). Relative risk of relapse in patients treated with
      amoxicillin/clavulanate was 2.6 greater compared to cefaclor. There were
      significantly higher rates of gastrointestinal adverse events in group treated
      with amoxicillin/clavulanate (29/97 patients; 29.89%) compared to cefaclor (16/95
      patients; 16.84%) - p< 0.03. Frequency of other adverse events did not differ
      significantly between the groups. CONCLUSIONS: Cefaclor and
      amoxicillin/clavulonate provide a clinically and bacteriologically effective
      treatment for patients with pharyngotonsillitis caused by GABHS, but cefaclor
      treatment is significantly safer in regard to gastrointestinal side effects.

PMID- 11535953
TI  - Comparative analysis of the effectiveness of misoprostol and prostaglandin E(2)
      in the preinduction and induction of labor.
AB  - BACKGROUND: Amniotomy and oxytocin infusion are the routine methods most
      frequently applied to induce labor. These methods are not effective when the
      cervix is unripe. Prostaglandins may accelerate the process of cervical ripening
      independently of the stimulation of uterine contractions, since they induce the
      formation of a gap junction (spread of excitation) and release uterine
      contractions. The purpose of this study is a comparative analysis of the
      effectiveness and safety of misoprostol and PGE2 in the process of cervical
      ripening and inducing labor in patients at full term delivery with a live fetus
      and indications for inducing labor due to an unripe uterine cervix. MATERIAL AND
      METHODS: The experimental group consisted of 30 patients at 38-41 weeks of
      gestation who received misoprostol administered into the posterior vaginal fornix
      (group M). The control group included 26 patients at 39-42 weeks of gestation in
      whom labor was induced using natural prostaglandin E(2) (group P). RESULTS: There
      were no statistically significant differences in maternal age, body weight and
      height, or uterine cervical ripening between the two groups of patients. The
      average time of gestation was 0.92 weeks shorter in group M. The time from
      administration of the drug to the onset of regular contraction activity of the
      uterus and delivery of an infant was shorter in the group of patients receiving
      misoprostol intravaginally. CONCLUSIONS: Our results would seem to indicate that
      misoprostol is an effective drug that can be used for elective preinduction and
      induction of labor. However, the application of this drug to induce labor with a
      live fetus requires special caution and care, as well as continuous
      cardiotocographic monitoring to assure the safety of both the mother and the
      infant.

PMID- 11535954
TI  - Assessment of human body composition using dual-energy x-ray absorptiometry and
      bioelectrical impedance analysis.
AB  - BACKGROUND: Human body composition, particularly the content of fat tissue and
      its distribution, has been extensively measured in healthy, diseased, obese and
      elderly subjects. A variety of non-invasive methods have been applied for these
      studies. Bioelectrical impedance analysis (BIA) is a commonly used method, based
      on the conduction of electrical current in the body and the differences in the
      ability to conduct electricity between the fat and water components of the body.
      Recently, dual-energy x-ray absorptiometry (DEXA) has been introduced for bone
      mass, bone mineral density and body composition studies. Unlike other methods,
      DEXA measures three components of the body: bone mineral content, fat tissue
      mass, and lean tissue mass, and additionally regional fat distribution. The
      objective of this study was to compare body composition as assessed by DEXA and
      BIA methods in a sample of 100 patients. MATERIAL AND METHODS: Body composition
      was studied in 100 consecutive subjects, 59 women and 41 men. The lean body mass
      (LBM), fat body mass (FBM), and percent body fat (%BF) were measured by the DEXA
      and BIA techniques. RESULTS: There were highly statistically significant linear
      relationships between LBM, FBM and %BF assessed by DEXA and BIA in both sexes
      (p<0.001 for all measurements). No influence of age or BMI on the relationship
      between DEXA and BIA results was observed. Differences were observed between DEXA
      and BIA measurements of both fat and fat-free tissue. The results suggest that
      DEXA may underestimate the LBM and overestimate body fat compared with BIA,
      probably due to different assumptions about the constants. CONCLUSIONS: We
      conclude that both methods are suitable for body composition studies.

PMID- 11535955
TI  - Imaging of bone in the diagnostics of renal osteodystrophy in children with
      chronic renal failure.
AB  - BACKGROUND: In the last two decades considerable advances have been made in the
      development of imaging tests of the skeletal system. This progress in diagnostic
      techniques, along with the growing availability of the tests, renders it
      necessary to review and evaluate their suitability for daily clinical practice.
      The aim of this article is to compare the results of radiological testing of bone
      with densitometrical, histomorphometric, and biochemical tests in children with
      chronic renal failure. MATERIAL AND METHODS: The research involved 31 children
      with renal failure, of whom 10 were being treated conservatively, 17 by
      continuous ambulatory peritoneal dialysis (CADO), and 4 by hemodialysis (HD). In
      all these children, radiological examinations of bone were performed in the arms,
      knees, and hips, along with tests for the serum concentration of parathormone
      (iPTH), calcium (Ca), and phosphates (P), and for the activity of alkaline
      phosphatase (AP). Bone density tests by the DXA method and bone biopsies were
      also performed. On the basis of radiological evaluation, the patients were
      divided into two groups: Group I, consisting of 14 children with a normal bone
      structure image, and Group II, consisting of 17 children with bone atrophy.
      RESULTS: No statistically significant differences were discovered in the mean
      values of the tested biochemical parameters between the two groups. The mineral
      density of total body was normal in 9 of the 14 patients in Group I (64%), and in
      7 of 17 (41%) from Group II. The mineral density of total lumbar spine gave
      similar results. Lower bone density results were obtained in Group II than in
      Group I, though only in the case of the lumbar spine were the differences
      statistically significant. In Group I, 5 cases were discovered of chronic
      osteodystrophy without osteomalacia and hyperparathyroidism (NB), 2 cases of
      adynamic bone disease (ABD), 4 cases of hyperparathyroidism (HP), 2 cases of
      moderate hyperparathyroidism (MHP), and one mixed form (Mix); in Group II, there
      were 6 NBs, 2 ABDs, 1 case of osteomalacia (OM), 5 HPs, and 3 mixed. Radiological
      examinations revealed one male in Group I with features of prior Perthes's
      disease, one with fibrous cortical defect, and four cases of valgity of the coxa
      valga. In Group II, there were 3 children with radiological changes typical for
      osteomalacia, and in 1 case typical radiological signs of hyperparathyroidism.
      CONCLUSIONS: Given the lack of consistency in the results of the tests here
      presented, an entire panel of available tests should be performed for the
      comprehensive evaluation of the status of the skeleton.

PMID- 11535956
TI  - Simplified antiviral prophylaxis with or and without artificial feeding to reduce
      mother-to-child transmission of HIV in low and middle income countries: modelling
      positive and negative impact on child survival.
AB  - BACKGROUND: Antiviral prophylaxis is recommended for HIV positive mothers to
      prevent mother-to-child transmission of HIV. To date UNAIDS and WHO policy has
      been based on a study in Thailand which showed a reduction in transmission by
      half with short course AZT (Zidovudine) treatment together with artificial
      feeding. We modelled the possible positive and negative effects on child deaths
      in low and middle resource developing country settings of two interventions to
      reduce mother to child transmission (MTCT) of HIV: antenatal testing, short
      course antivirals (zidovudine or nevirapine), firstly with and then without
      artificial feeding. MATERIAL AND METHODS: Estimates are made of child lives
      likely to be saved by the programme by age ten years, balanced against increases
      in deaths due to more uninfected mothers choosing to use artificial feeds where
      these are part of the intervention. Mid-point values for variables affecting the
      balance of mortality gains and losses are taken from recent published data for
      low and middle income developing countries and a sensitivity analysis is
      undertaken. RESULTS: In low income settings the use of antivirals alone would
      result in an estimated gain in child survival of around 0.36%, representing 360
      deaths avoided from a birth cohort of 100,000 by age 10 years. Adding artificial
      feeding could reduce the gain to 0.03% (30 deaths avoided). In middle income
      settings the gain from antivirals alone would be 0.26% but as 'spill-over' of
      artificial feeding to uninfected women was more likely it could result in a net
      increase of child deaths of up to 1.08% (1,080 additional deaths). A sensitivity
      analysis emphasised this potential for regimens using artificial feeding if
      progamme participation was low, and under most circumstances in middle income
      settings. CONCLUSIONS: HIV testing and use of antivirals by infected mothers, if
      well implemented, will be effective at a population level in reducing MTCT.
      However the addition of artificial feeding is potentially be a high risk
      strategy, especially in middle income countries.

PMID- 11535957
TI  - Evaluation of the unlinked anonymous prevalence monitoring programme for HIV in
      England and Wales: science, ethics and health policy.
AB  - BACKGROUND: The Unlinked Anonymous Prevalence Monitoring Programme for HIV in
      England and Wales was set up in 1989 and has been operational for over a decade.
      This paper describes a wide-ranging evaluation of the programme encompassing
      different perspectives and approaches: epidemiological, ethical, social
      scientific and economic. MATERIAL AND METHODS: Epidemiological and ethical
      evaluation by critical review of the literature. Evaluation of the public's views
      on unlinked anonymous testing of blood by questions inserted into the Omnibus
      National Survey carried out by the Office for National Statistics. Evaluation of
      the views of planners of HIV/AIDS services by telephone questionnaire survey.
      Economic analysis by costing of the programme. RESULTS: Epidemiologically the
      programme's results contribute to the jigsaw of knowledge about HIV. The ethical
      debate has shifted with time, and moral justification for the programme was more
      valid at its inception than now. The majority of the public was unaware of
      unlinked anonymous testing of blood for HIV, and 25-30% disagreed with the
      policy. Local planners of HIV services found the programme generally useful.
      There are concerns about the programme's hidden costs and funding. CONCLUSIONS:
      To improve awareness and respect autonomy information leaflets, explaining opting
      out of testing, should be handed to all individuals at centres where the
      programme is operational. Data from the programme should be fed back quicker to
      local planners, and the programme's funding needs reappraisal. Further research
      on patients' views is indicated. Generic conclusions include the need for a
      definition of 'public health emergency', and establishment of a national
      healthcare ethics committee.

PMID- 11535958
TI  - The 'railway spine'--a precursor for the 'whiplash syndrome'?

PMID- 11535959
TI  - Cell surface estrogen receptors coupled to cNOS mediate immune and vascular
      tissue regulation: therapeutic implications.
AB  - The vast number of reports dealing with estrogen and its associated molecular
      signaling cascades deal with genomic processes. However, recently data is
      emerging that demonstrates that estrogen may also work via estrogen cell surface
      receptors. In this regard, we describe such receptors on human monocytes,
      granulocytes and vascular endothelial cells. It would appear that these receptors
      are coupled to constitutive nitric oxide synthase derived nitric oxide release
      via the stimulation of intracellular calcium transients. It is this cascade that
      has the ability to down regulate both immune and vascular cellular processes, i.
      e, adherence. Based on this, for example we surmise that in menopause an earlier
      initiation of estrogen therapy may be more beneficial so as to prevent a decrease
      in its cellular signaling and maintenance functions, at least with respect to NO
      related events.

PMID- 11535960
TI  - Clinically important factors influencing endothelial function.
AB  - The endothelium, a continuous cellular monolayer lining the blood vessels, has an
      enormous range of important homeostatic roles. It serves and participates in
      highly active metabolic and regulatory functions including control of primary
      hemostasis, blood coagulation and fibrinolysis, platelet and leukocyte
      interactions with the vessel wall, interaction with lipoprotein metabolism,
      presentation of histocompatibility antigens, regulation of vascular tone and
      growth and further of blood pressure. Many crucial vasoactive endogenous
      compounds like prostacyclin, thromboxane, nitric oxide, endothelin, angiotensin,
      endothelium derived hyperpolarizing factor, free radicals and bradykinin are
      formed in the endothelial cells to control the functions of vascular smooth
      muscle cells and of circulating blood cells. These versatile and complex systems
      and cellular interactions are extremely vulnerable. The balances may be disturbed
      by numerous endogenous and exogenous factors including psychological and physical
      stress, disease states characterized by vasospasm, inflammation, leukocyte and
      platelet adhesion and aggregation, thrombosis, abnormal vascular proliferation,
      atherosclerosis and hypertension. The endothelial cells are also the site of
      action of many drugs and exogenous toxic substances (e.g. smoking, alcohol). As
      markers and assays for endothelial dysfunction, direct measurement of nitric
      oxide, its metabolites from plasma and urine, functional measurement of vascular
      nitric oxide dependent responses and assay of different circulating markers have
      been used. In numerous pathological conditions (e.g. atherosclerosis,
      hypertension, congestive heart failure, hyperhomocysteinemia, diabetes, renal
      failure, transplantation, liver cirrhosis) endothelial dysfunction has been
      described to exist. Some of them, as well as hormonal and nutritional factors and
      drug treatment will be discussed in this short review.

PMID- 11535961
TI  - Assessing the effect of patient and prescriber preference in trials of treatment
      of depression in general practice.
AB  - Preferences include the choices made by individuals when presented with options
      for treatment for depression, and the system of beliefs and views that underlies
      those choices. They are informed by the experience of previous treatment by
      individuals, their family and friends, information from medical professionals and
      the media, and incorporates biases and ideologies present within the population.
      Although the randomised controlled trial is generally considered to be the
      optimal method for evaluating the effectiveness of health care interventions, [1]
      patients may become less motivated to follow the treatment protocol if they are
      not allocated to their preferred treatment. Consequently, the relevant arms of
      the study may appear less effective as a result. Further, following an invitation
      to join a clinical trial, patients may refuse randomisation and be excluded from
      the trial if they have strong treatment preferences, leading to the introduction
      of bias and restricted ability to generalise the results, as participants may not
      be representative. Considerable demand has been shown by patients for
      psychological treatments for the treatment of depression in primary care.
      However, two recent studies have not demonstrated a relationship between being
      allowed to choose treatment and short-term depression outcome. These two studies
      explored primary care patients treated with antidepressants or counselling, and
      non-directive counselling, cognitive-behaviour therapy or usual general
      practitioner care. Further work is needed to determine the effects of preferences
      within different study designs and to explore the views of both professionals and
      patients using appropriate qualitative designs.

PMID- 11535963
TI  - Vertebral fractures: a hidden problem of osteoporosis.
AB  - Osteoporosis is a progressive skeletal disease, which in many cases remains
      silent and asymptomatic until a fracture occurs. Vertebral fractures are the
      earliest and most common osteoporotic fractures. The prevalence of vertebral
      fractures increases steadily with age, ranging between 20% for 50-year-old
      postmenopausal women to 64.5% for older women. The majority of vertebral
      fractures are not connected with severe trauma, and only one in three is
      diagnosed clinically. Usually vertebral fractures are associated with such
      clinical symptoms as back pain, posture change, loss of height, functional
      impairment, disability, and diminished quality of live. Women with the most
      severe vertebral fractures are the most likely to incur further fractures, with
      as much as 3.4 times the risk of hip fracture, and 12.6 times the risk of new
      vertebral fractures. Almost 20% of women will experience another fracture within
      1 year after a vertebral fracture. Vertebral fractures are accompanied by
      increased mortality. The relative risk of death following vertebral fracture is
      almost 9 times higher. The most important purpose of osteoporosis management in
      postmenopausal women is prevention of the first vertebral fracture. Raloxifene
      (Evista) is the only SERM approved by the American FDA for the treatment and
      prevention of osteoporosis. It is the first compound with selective estrogen
      agonist activity in bone and in the cardiovascular system, but with estrogen
      antagonist activity or no activity in reproductive tissues and breast. Raloxifene
      reduces the risk of positive estrogen receptor breast cancer, decreases total
      cholesterol and LDL cholesterol, increases HDL cholesterol, does not increase the
      risk of endometrial cancer or cause bleeding and spotting. After 3 years of
      treatment Raloxifene reduces the risk of first vertebral fracture by 55%. The
      fracture risk within one year is reduced by as much as 68%. Continued observation
      has proved its sustained efficacy in the further reduction of fracture risk by
      49% in the fourth year. Raloxifene treatment does not change the physiological
      structure of bone quality and does not cause fibrosis, osteomalacia or other
      toxic effects.

PMID- 11535962
TI  - Cancerogenesis in Helicobacter pylori infected stomach--role of growth factors,
      apoptosis and cyclooxygenases.
AB  - BACKGROUND: Epidemiological and animal studies demonstrated a link between
      gastric cancer (GC) or mucosal associated lymphoid tissue (MALT) lymphoma and
      chronic infection with Helicobacter pylori (H. pylori). The exact mechanism
      responsible for the development of GC and MALT-lymphoma in H. pylori-infected
      patients still remains obscure. This report is designed to overview the molecular
      biology, especially the gene expression and histochemical manifestation of
      gastrin and other growth factors such as transforming growth factor alpha (TGF
      alpha) and hepatocyte growth factor (HGF) in the GC before and after eradication
      of H. pylori. Furthermore, gene expression of cyclooxygenase-1 (COX-1) and COX-2
      and apoptosis-related proteins such as Bax and Bcl-2 are discussed. MATERIAL AND
      METHODS: The findings originate from two series of patients; Series I involving
      337 GC patients and 400 age- and gender-matched controls and series 2 including
      20 MALT-lymphoma patients and 40 matched controls. RESULTS: An overall H.pylori
      seropositivity reached about 80% in GC and about 90% in MALT-lymphoma,
      significantly higher than in non-cancer controls (60%). The prevalence of CagA
      positive strains was about twice as high (about 70%) in GC and MALT-lymphomas as
      in sex- and age-matched controls. Expression of gastrin was detected in antrum of
      all tested patients but also in majority (90%) of GCs and MALT-lymphomas tumor
      tissue. HGF and TGF alpha were expressed more frequently in GC tissue than in
      normal fundic mucosa. COX-1 was similarly expressed in GC and MALT as in intact
      mucosa, while COX-2 mRNA was detected only in tumor tissue, being attenuated by
      H.pylori eradication in GC and abolished by this therapy in MALT-lymphoma. The
      plasma levels of alpha-amidated gastrin in GC and MALT were several folds higher
      than in controls. Gene expression of bcl-2 was detected in all, while bax--only
      in about 50% of GC samples. CONCLUSIONS: Infection with H. pylori, especially
      that expressing CagA-positivity, is primum movens in developing GC and MALT
      lymphoma and the upregulation of growth factors, particularly of gastrin, and COX
      2 and dysregulation of the Bax/Bcl-2 system seem to contribute to gastric
      cancerogenesis.

PMID- 11535965
TI  - [Renal protection with amifostine during intraoperative peritoneal
      chemohyperthermia (IPCH) with cisplatin (CDDP) for peritoneal carcinosis. Phase 1
      study].
AB  - BACKGROUND: An innovative approach to peritoneal neoplasm therapy is based on the
      surgical exeresis of visceral neoplasms, peritonectomy and lastly perfusion of
      the abdominal cavity with cytostatic drugs in hypothermia (1PCH). Cisplatin
      (CDDP) is one of the most frequently used drugs for peritoneal perfusion owing to
      its excellent synergy with hypothermia, reduced ability to penetrate the
      peritoneal- plasma barrier and its demonstrated efficacy against the majority of
      neoplasms causing peritoneal carcinosis. A major restriction is that CDDP causes
      renal toxicity. In order to minimise the risk of renal damage, the authors
      studied the use of amifostin to protect the renal system. A phase-1 study was
      performed to find the dose of amifostin that guarantees effective renal
      protection without causing hypotension. METHODS: A total of 67 cytoreductions
      were performed at our centre associated with abdominal cavity perfusion using
      cytostatic compounds in hyperthermia (1PCH) with CDDP for peritoneal carcinosis.
      Among the first 9 patients undergoing IPCH without nephroprotection, Grade 2
      (WHO) renal toxicity was observed in 4 cases (44%) and Grade IV-WHO toxicity in
      one patient (11%) leading to hemodialysis and death. Arnifastin was then
      administered to 18 patients. The administration protocol was as follows:
      cytoreduction, im. administration of amifostin 910 mg/m2 in 15 minutes, execution
      of IPCH. All patients treated using this dose presented hypotension with systolic
      arterial pressure <70 mmHg and amifostin administration was consequently
      suspended. Amifostin was then administered to a further 18 patients divided into
      groups of three. The dose used for the first triplet was 400 mg/m2; we then
      increased the dose by 50 mg/m2 in each subsequent triplet. The maximum dose
      tolerated was 50 mg/m2 less than the initial dose that caused systolic pressure
      to fall below 70 mmHg. RESULTS: Patients treated with doses = or <500 mg/m2 did
      not present hypotension and it was therefore possible to administer the entire
      dose. Patients treated with 600 mg/m2 of amifostin all presented hypotension <70
      mg Hg, leading to the suspension of the drug. A new triplet of patients was
      treated at a dose of 550 mg/m2 and none showed hypotension. Taking 550 mg/m2 as
      the maximum tolerable dose, a further 22 patients then received amifostin
      infusion with 550 mg/m2 prior to IPCH. Creatinemia was assayed daily for two
      weeks and creatinine clearance was measured twice a week to evaluate the efficacy
      of nephroprotection. None of the patients treated with amifostin during the study
      died from causes correlated to renal failure: 1 patient died from TEP and 1 from
      septic shock. No patient treated with a dose of 550 mg/m2 developed arterial
      hypotension. None of the 18 patients in the dose-finding study presented
      postoperative creatinemia >1.6 (WHO grade 1 toxicity). In the group of 22
      patients treated later, 2 cases (9%) presented creatinemia >1.6 (1.8 and 2.1) for
      a few days; both had undergone severe debulking and one of the patients
      subsequently underwent resection and anastomosis of the left renal artery invaded
      by the neoplasm. CONCLUSIONS: Some patients undergoing cytoreduction+IPCH without
      the use of amifostin developed severe renal toxicity; acute renal failure
      occurred in 1 patient requiring hemodialysis and was the main cause of death.
      None of the 28 patients treated with amifostin 550 mg/m2 developed hypotension or
      renal insufficiency; only 2 cases showed a slight transient increase in renal
      function markers. Amifostin appears to be an effective drug for protecting renal
      emunctory from the toxic effects of CDDP used in cytoreduction+IPCH in patients
      with peritoneal carcinosis. The dose of 550 mg/m2 used in this study does not
      cause hypotension and is recommended for this type of clinical use.

PMID- 11535966
TI  - Current treatment of hypertension.
AB  - Numerous national hypertension guidelines are available. Major similarities and
      differences have been reviewed, along with both patient and provider barriers to
      adequate blood pressure control. The current recommended risk stratification of
      hypertension for treatment decisions together with principles of drug management
      have been reviewed. Finally, data from recent clinical trials in hypertension
      together with the lessons learned from those trials have been addressed. It is
      apparent that most available classes of antihypertensive agents can be effective
      in the management of hypertension, if used appropriately by providers, in
      conjunction with optimal adherence with prescribed medications by patients.

PMID- 11535967
TI  - [Lithiasis of the gallbladder and biliary ducts: from epidemiology to therapy].
AB  - The diagnosis of cholelitiasis, more and more common with the wide diffusion of
      abdominal ultrasound, is often a surprise for the patient as well as for the
      physician who is sometimes forced to take a therapeutical decision. In the case
      of dilatation of the biliary duct, the cholangioRM is assuming an increasingly
      important role, especially before a therapeutical ERCP. The best therapeutical
      approach seems to be the surgical ablation in laparoscopy in presence of specific
      signs and symptoms. Indication to surgical ablation is a symptomatic or
      complicated cholelithiasis, or the history of obstructive pancreatitis. A
      preventive cholecystectomy can be useful for precancerous lesions.

PMID- 11535968
TI  - [Treatment of visceral leishmaniasis].
AB  - Aim of this report is to review the most important therapeutical choices in
      visceral leishmaniasis. The pentavalent antimonial derivatives (PAD) remain the
      first-line drugs despite the toxicity and the wide resistance. Among the other
      therapeutical options, the importance of lipid formulations of amphotericin B is
      emphasized; it is a valid resource for the treatment of leishmania-HIV co
      infection in the European Mediterranean Countries; instead, due to the high cost,
      it cannot be proposed in developing Countries. Besides, the characteristics of
      other drugs are evaluated: pentamidine, aminosidine, miltefosine, allopurinol,
      ketoconazole, gamma-interferon; such options propose different validity in
      different geographical regions. Among these, interesting results are reported for
      miltefosine, both for efficacy and practicality of use. Finally, the importance
      of a vaccination strategy in endemic areas of developing Countries is underlined.

PMID- 11535969
TI  - [Use of clodronic acid in mineral metabolism conditions: state of the art in
      2000].
AB  - Clodronic acid is a non-aminate bisphosphonate capable of inhibiting bone
      resorption. Pharmacological and clinical trials have shown the efficacy of
      clodronic acid in the treatment of post-menopausal osteoporosis and in all
      conditions of excess bone resorption, such as Paget's disease, malignant tumoral
      hypercalcemia and osteolytic metastases. Clodronic acid is the only
      bisphosphonate currently on the market available for both oral and parenteral
      administration. Intramuscular therapy with clodronic acid at a dose of 100
      mg/week has shown significant effects on bone mineral density after 6 months
      treatment in patients with postmenopausal osteoporosis and these effects were
      maintained 3 years after the start of treatment. Increased bone mass is
      associated with a reduced risk of the onset of vertebral fractures. In a recent
      three-year study a significant increase was observed in bone mineral density
      associated with a 46% reduction in the incidence of vertebral fractures. The
      reduction in bone pain after parenteral treatment with clodronic acid is an
      important added value in the use of this molecule in osteopenic pathologies.
      Moreover the costs of parenteral clodronic acid treatment is certainly
      competitive compared to other drugs. Oral and parenteral clodronic acid was well
      tolerated in clinical trials. Gastrointestinal adverse effects were described
      only with high oral doses. These effects were transient and generally resolved
      without interrupting the treatment. Clodronic acid is an effective and well
      tolerated drug able to inhibit bone resorption. The low incidence of undesired
      effects at a gastroenteric level, the possibility of formulas for parenteral
      administration, the antalgic effect and low costs make clodronic acid an
      extremely interesting molecule for the prevention and treatment of postmenopausal
      osteoporosis and all conditions of excessive bone resorption, such as Paget's
      disease, malignant tumoral hypercalcemia, osteolytic metastasis and
      hyperparathyroidism.

PMID- 11535970
TI  - Oral neltenexine in patients with obstructive airways diseases: an open,
      randomised, controlled comparison versus sobrerol.
AB  - BACKGROUND: The synthetic mucolytic neltene-xine is an amide derivative of
      ambroxol and thiophencarboxylic acid. The aim of this open, randomised,
      controlled study versus sobrerol was to evaluate the efficacy and tolerability of
      neltenexine (oral granules in sachets) as compared with sobrerol (oral granules
      in sachets), administered to patients with obstructive airways disease. METHODS:
      Thirty male and female patients were recruited. The exclusion criteria were
      allergy to neltenexine or sobrerol, an assessed diagnosis of severe bronchospasm
      requiring beta2-agonists, corticosteroids or aminophylline, pregnant or nursing
      women, cystic fibrosis, active tuberculosis or an assessed diagnosis of
      bronchiectasis. No infections of other organs (such as urinary tract infections)
      were present at baseline. Concomitant treatment with antitussives or other
      mucolytic agents was not allowed during the course of the study. Fifteen patients
      were randomised to treatment with neltenexine, 1 sachet thrice daily for 20 days
      orally (neltenexine group) and 15 patients to treatment with sobrerol, 1 sachet
      thrice daily for 20 days orally (sobrerol group). The efficacy parameters were:
      sputum characteristics and volume, difficulty in expectorating, cough, dyspnoea,
      pulmonary auscultation. Tolerability was monitored and adverse events were
      reported. RESULTS: The study highlighted that neltenexine has a good efficacy in
      the treatment of patients with obstructive airways disease entailing significant
      impairment of clinical parameters. CONCLUSIONS: Neltenexine can be an effective
      therapeutic alternative to sobrerol.

PMID- 11535971
TI  - Neltenexine tablets in smoking and non-smoking patients with COPD. A double
      blind, randomised, controlled study versus placebo.
AB  - BACKGROUND: The aim of this double-blind, randomised, controlled study vs placebo
      was to evaluate the efficacy and tolerability of neltenexine (tablets) versus
      placebo (tablets), administered to smoking and non-smoking patients with chronic
      obstructive pulmonary disease (COPD). METHODS: Sixty patients with mild stable
      COPD were recruited. The exclusion criteria were lung cancer, pulmonary
      tuberculosis, asthma, cystic fibrosis, bronchiectasis, community-acquired
      pneumonia (CAP), intercurrent infections, concomitant treatment with
      corticosteroids, antitussives, beta2 agonists, anticholinergic and other
      mucolytic agents. The patients were allocated randomly to receive neltenexine (20
      smokers and 20 non-smokers) or a matching placebo (20 smokers), 1 tablet twice
      daily for 20 days. The efficacy criteria were sputum characteristics and volume,
      difficulty in expectorating, cough, dyspnoea, pulmonary auscultation, forced
      expiratory volume in one second (FEV1), vital capacity and arterial partial
      oxygen pressure (PO2). Tolerability was monitored and adverse events were
      reported. RESULTS: At the study end, the improvement of patients treated with
      neltenexine (smokers and non-smokers) was greater and statistically significant
      as compared with the patients in the placebo group in terms of improvement of
      dyspnoea (p<0.02), cough (p<0.02), pulmonary auscultation (p<0.02), and
      difficulty in expectorating (p<0.02). Furthermore, a significant improvement of
      the sputum characteristics (p<0.02) and volume (p<0.01) was evidenced, as
      compared with patients treated with placebo, in non smoking patients treated with
      neltenexine and in smoking patients treated with neltenexine. CONCLUSIONS: The
      study confirmed earlier clinical experiences showing that neltenexine is
      effective in the treatment of COPD patients and highlighted the correlation
      between abstention from smoking and the efficacy of mucoactive treatment.

PMID- 11535972
TI  - [Erectile dysfunction after non-nerve sparing radical pelvic surgery.
      Therapeutical experience with sildenafil and L-arginine evaluated by Buckling
      test].
AB  - BACKGROUND: Patients undergoing radical pelvic floor surgery are often find that
      sexual function is impaired. In this research hypothesis, we evaluated the
      efficacy of alternative therapy to conventional PGE 1 injections, such as the
      association of Sildenafil and L-Arginine. This association is based on the
      principle that L-Arginine, the precursor of nitric oxide, improves the effect of
      Sildenafil, which is effective in the presence of nitric oxide. METHODS: The
      experimental plan was to make a comparative study between 2 random groups of
      patients selected from those undergoing radical cystectomies and prostatectomies
      over the past three years. 116 patients were eligible (64 prostatectomies and 52
      cystectomies). The first random group was treated with Sildenafil alone and the
      second with Sildenafil and L-Arginine. The efficacy of treatment was evaluated
      using the Buckling test (pressure threshold of cavernous flexation at penile
      axial rigidity) once after ambulatorial administration and then by telephone
      interview (subjective evaluation) after administration at domicile. RESULTS: The
      starter dose was 50 mg and was inefficient in both groups (Buckling test between
      0 and 250). 100-mg doses gave significant results (Buckling test >500) in both
      groups, especially the second. Cardiopathic patients, diabetics and patients with
      retinal disorders or who were unmotivated were excluded from the study. The mean
      age of patients was 65. CONCLUSIONS: The resumption of relatively satisfactory
      sexual activity was demonstrated using non-invasive pharmacological treatment.

PMID- 11535973
TI  - Treatment of infrabony pocket with a collagen membrane supported by cancellous
      bovine bone.
AB  - BACKGROUND: Treatment of infrabony pockets with guided tissue regeneration (GTR)
      methods using absorbable membranes supported by bone substitutes has gained wide
      acceptance. Our objective is to observe the clinical variations obtained with the
      use of these materials in a prospective clinical study. METHODS: Nine patients
      were treated with GTR at nine infrabony pockets using a double layered collagen
      membrane and deproteinized cancellous bovine bone associated with root
      conditioning by application of tetracycline-HCl. The nine patients included in
      this study had adult periodontitis, were non-smokers and responded well to
      initial therapy. The sites evaluated had probing pocket depths of at least 5 mm
      and an angular defect of at least 2 mm. The clinical parameters considered were
      probing pocket depth (PPD), clinical attachment level (CAL) and gingival
      recession (REC). Some indexes were also evaluated: the modified Quigley and
      Hein's Plaque index (PI), O'Leary's bleeding index (FMBS) and the Loe and
      Sillness gingival index (GI). These parameters were measured one week before
      surgery and at the control visit after an average of 22.9 months. After the
      removal of the sutures on the eighth day the patients received professional oral
      hygene every four months at their private dentists' offices. The baseline and the
      final measurements were compared with the Student OtO-test to verify the
      statistical significance of this case series. RESULTS: The mean values of PI,
      FMBS and GI remained unvaried (p>0.05). Results showed an average decrease in PPD
      of 4.0+/-2.7 mm (p=0.0002), an average increase of CAL of 4.1+/-2.1 mm (p=0.0001)
      and an average decrease in recession of 0.2+/-1.2 mm (p=0.594). The value of
      statistical significance was set at p=0.05. CONCLUSIONS: We can conclude that the
      materials used in this study behaved well clinically and that the surgical
      technique described has given results that, within the limits of the number of
      cases reported, has modified the PPD and CAL in a significant manner.

PMID- 11535974
TI  - [Estimating facial asymmetries in individuals with malocclusion and
      normocclusion].
AB  - BACKGROUND: The en face photographs taken in standard conditions were used to
      examine the facial symmetry in examinees with normocclusion and malocclusion.
      METHODS: A total of 80 examinees were included in the study (40 of whom had
      normocclusion and another 40 had malocclusion) without any prior orthodontic
      therapy. The face was divided into six squares by the mediosagittal line drawn
      through the Trihion, Glabella, Subnasals and Gnathion as well as by horizontal
      lines drawn through the same points. The four lower squares - the middle and the
      lower thirds of the face were taken into account to analyse facial symmetry. The
      symmetry between individual squares was measured by applying transparent paper
      with a millimetre-sized squares web and a planimetry. RESULTS: The results did
      not show any asymmetry between left and right parts of the face in either group
      of examinees. CONCLUSIONS: A high correlation was established among all the
      analysed variables.

PMID- 11535975
TI  - Sjogren's syndrome: direct immunofluorescence in diagnosis.
AB  - BACKGROUND: Sjogren's syndrome (SS) is an autoimmune inflammatory exocrinopathy.
      In the classical clinical presentation, diagnosis is readily achieved but this is
      less easy in early disease or oligosymptomatic forms. METHODS: We have used
      direct immunofluorescence (d.i.f.), with IgG antibodies, comparing salivary gland
      biopsies from subjects with SS compared with control subjects. RESULTS: Direct
      immunofluorescence, using antibodies anti-IgG and demonstrating positivity for
      all the examined champions of SS while it is negative for control biopsies.
      CONCLUSIONS: Direct immunofluorescence, on salivary glands by biopsy, can be
      considered a valid additional aid to the diagnosis of subclinical SS.

PMID- 11535976
TI  - [Pleomorphic adenoma of the parotid gland in childhood].
AB  - BACKGROUND: The authors report the results of ten years' activity at the
      Pedodontic Surgery Unit in the Institute of Maxillofacial Surgery at the Second
      University of Naples and analyse the possibility of conservative treatment of
      pleomorphic adenoma in childhood. METHODS: The study includes 614 cases of
      salivary gland pathology. The authors illustrate the epidemiological, clinical
      and therapeutic characteristics of this type of lesion in childhood, emphasising
      that the data emerging from this study do not differ from the clinical and
      therapeutic management of pleomorphic adenoma in young patients reported in the
      literature. RESULTS: In particular, they emphasise that satisfactory therapeutic
      results can be achieved using conservative techniques, like conservative
      superficial parotidectomy. CONCLUSIONS: Conservative superficial parotidectomy
      has the advantage of being less radical and traumatic for a young patient,
      without provoking a significant increase in recidivation.

PMID- 11535977
TI  - Geographic tongue (migrant glossitis) and psoriasis.
AB  - BACKGROUND: The aim of this study was to examine the relationship of geographic
      tongue to psoriasis. METHODS: We report a comparative study on two groups of
      patients: the first (20 patients) with cutaneous psoriasis and lesions of the
      oral mucosa similar to geographic tongue; the second (20 patients), with benign
      migratory glossitis only. Biopsy samples of the lingual mucosa were taken from
      both groups. RESULTS: The histologic examination of oral biopsies from the first
      groups showed typical features of psoriasis. The second group showed the same
      features of psoriasis in 80% of patients. CONCLUSIONS: The clinical and
      histopathologic findings support the hypothesis that migrant glossitis can be
      considered an expression of oral psoriasis.

PMID- 11535978
TI  - [Systemic antimicrobial treatment of prosthesis related infections: a comparative
      study of ornidazole and minocycline. A microbiological evaluation and
      experimental protocol].
AB  - BACKGROUND: The aim of this study was to evaluate the efficacy of two
      chemotherapeutic agents against bacterial forms responsible for prosthesis
      related infections. METHODS: The evaluation was made on the basis of a count
      using optical microscope 1000x after GRAM staining of the main bacterial forms
      found in periprosthetic inflammatory exudate both before and after treatment. Two
      drugs used: ornidazole and minocycline. A group of 20 patients were studied (12
      women and 8 men) aged between 42 and 71 years old with an advanced stage of
      periprosthetic inflammatory pathology. The pharmacological protocol was
      administered to the two groups of patients for a period of approximately 15 days.
      RESULTS: At the end of treatment there was a marked reduction in all the
      bacterial forms involved in periprosthetic pathology in both groups, with a
      gradual recovery of normal bacterial flora (gram forms) coupled with a clinical
      improvement in the implant sites examined. CONCLUSIONS: Given the specificity of
      action shown by ornidazole against pathogenic anaerobic, gram-; bacteroides and
      sporigenic forms, it is recommended for systemic use against prosthesis-related
      inflammatory disease.

PMID- 11535979
TI  - [Gardner's syndrome. A case report].
AB  - Gardner's syndrome is a congenital condition characterised by diffuse intestinal
      adenomatous polyposis (IAP) associated with maxillary osteomas, odontomas,
      hypertrophy of the retinal epithelium and skin tumours. It may affect subjects of
      all ages with equal frequency in males and females. The fact that diffuse
      adenomatous polyposis, the most serious clinical aspect of the syndrome, is
      treated surgically, has led to improved survival in patients and, consequently,
      an increased incidence in associated lesions, particularly maxillary osteomas. A
      personal case observed at the Odontostoma-tological Clinic of the University of
      Rome La Sapienza is reported.

PMID- 11535980
TI  - [Extracorporeal shock wave lithotripsy in the treatment of salivary calculi. Our
      experience. Note 2].
AB  - In this study the authors, making use of a non-surgical therapeutic method like
      extracorporeal shock wave lithotripsy, aim to show the advantages of this method
      compared with surgery, in the therapy of lithiasis of the salivary glands. Seven
      patients suffering from calculi of the salivary glands were treated. The authors
      obtained the best result in each patient and in 5 of these obtained the complete
      disappearance of sialolithiasis. The authors, considering that there is an ever
      higher number of requests for this treatment, put extracorporeal lithotripsy in
      the foreground in the therapy of sialolithiasis.

PMID- 11535981
TI  - Early-stage epithelial ovarian cancer: an overview.
AB  - The clinical treatment of malignant epithelial ovarian cancer limited to the
      gonad(s) involves many problems that have given rise to analyses in recent
      literature and to different approaches: i. intensive anatomo-radio-surgical
      staging, evaluation and clinical incidence of prognostic risk factors; ii. re
      staging of patients after inadequate and incomplete surgery; iii. indications,
      role and topicality of second-look surgery; iv. conservative surgery in patients
      of a fertile age wishing to have children and retain activity of the gonads; v.
      laparoscopic surgery for treatment, staging, re-staging and surveillance; vi. the
      lymph node issue; vii. adjuvant therapy: indications, options, type of drugs,
      doses and length; viii. quality and frequency of surveillance; ix. malignant
      epithelial ovarian cancer limited to the gonads in pregnancy. The clinical
      handling of these tumours entails many complex problems causing emotional
      involvement since it is most frequent at a fertile age.

PMID- 11535982
TI  - Surgery of advanced malignant epithelial tumours of the ovary.
AB  - Surgery is still the cornerstone in the management of advanced epithelial ovarian
      cancer (AEOC) patients. It involves: i. establishment of diagnosis and staging;
      ii. primary cytoreduction; iii. interval cytoreduction, interval debulking
      surgery (IDS) or surgery after neoadjuvant chemotherapy; iv. secondary
      cytoreduction during the assessment of the status of the disease at the end of
      primary chemotherapy - second look; v. surgery for recurrence; vi. palliation.
      Substantial evidence exists to demonstrate that if surgery is performed by
      gynaecologists with a special training in gynaecological oncology, a survival
      advantage can be achieved when compared with that obtained when general surgeons
      are primarily treating AEOC. Primary surgery with diagnostic and cytoreductive
      intent should be performed in accordance with the European Guidelines of Staging
      in Ovarian Cancer. Whether or not cytoreduction should systematically include
      lymphadenectomy is still a controversial issue. The strong correlation between
      chemosensitivity, successful debulking surgery and survival strongly support the
      concept that it is the biological characteristic of the disease rather than the
      aggressiveness of the surgeon to allow a successful cytoreduction to the real
      optimal disease status. It should be now recognised as the complete absence of
      disease at the end of the surgical procedure. Both IDS and neoadjuvant
      chemotherapy represent a strong effort to achieve such a status through less
      morbidity and a better quality of life for the patient. Surgery for recurrence
      and palliation need to be optimised both in terms of patient selection and a
      better integration with chemotherapy and ancillary management.

PMID- 11535983
TI  - Medical therapy of advanced malignant epithelial tumours of the ovary.
AB  - Despite improvements seen in median and overall survival using a combination of
      platinum-compounds and paclitaxel (PTX), long-term survival rates for patients
      with advanced epithelial ovarian carcinoma remain disappointing and ongoing
      efforts have aimed to develop more effective primary therapy. In the early 1990Os
      the drug PTX was first tested in ovarian cancer. In the Gynaecological Oncology
      Group (GOG) trial 111 the cisplatin (CP)+PTX regimen was judged to be superior
      compared to the platinum-based control arm with an improvement of overall
      response rate, median progression-free interval and overall median survival.
      These favourable data were confirmed by a European-Canadian Intergroup trial
      (OV10). In contrast, in a further GOG trial (GOG132) there was no difference in
      survival between CP alone and the combination of PTX and CP. The International
      Collaborative Ovarian Neoplasm Study (ICON)3 is the first and only trial
      comparing PTX plus carboplatin against carboplatin alone or a (non-taxane) CP
      based control arm. The last analysis performed with a total of 1,293 events
      showed an estimated absolute difference in one-year progression-free survival of
      1% and in two-year overall survival of 2% both in favour of PTX plus carboplatin.
      The results of ICON3, in accordance with GOG132 study, appear to contradict the
      earlier positive results seen for PTX and CP in the GOG-111 and OV10 trials and
      suggested that single agent carboplatin, CY-adriamycin-CP are safe and effective
      first-line treatments for women requiring chemotherapy for ovarian cancer. A meta
      analysis with individual patient data is warranted to better clarify the issue of
      PTX in the front line therapy of advanced ovarian cancer. Salvage chemotherapy is
      often utilised in patients with advanced ovarian cancer, due to the high
      frequency of recurrent disease even after a clinical or pathological complete
      response after primary chemotherapy. Main objectives of salvage chemotherapy
      include: i. improvement in quality of life and symptoms; ii. tumour load
      reduction and survival advantage; iii. evaluation of potentially active new drugs
      to be included in first-line. Since the goal is palliation in most cases,
      monotherapy is generally indicated. However, the chances of response are directly
      related to the treatment-free interval, with a response rate nearly equivalent to
      that of primary chemotherapy when the treatment-free interval exceeds 24 months.
      Extension of the platinum-free interval before re-treatment with platinum or
      taxanes may allow partial reversal of resistance to these agents which can
      therefore still show significant activity in relapsing patients. Unfortunately,
      durable response to salvage chemotherapy is rare and cure is almost impossible.
      The sequential use of the agents currently available for salvage treatment in
      monotherapy may transform ovarian cancer into a chronic disease and confers long
      survival to the patients. Perhaps, the most interesting role of second-line
      chemotherapy is to identify new potentially active drugs, which can be moved up
      front. Most of the compounds used in second line (gemcitabine, topotecan,
      liposomal doxorubicin) are in fact under investigation to develop alternative
      schedules and sequences of drug administration. A new phase III multi-national
      randomised study for patients with advanced stage epithelial ovarian or primary
      periperitoneal carcinoma will evaluate the impact of incorporating a new drug
      within either a platinum-based triplet (new drug + platinum + PTX) or a
      sequential-doublet (new drug + platinum followed by platinum + PTX) in order to
      identify one or more experimental regimens able to improve long-term survival
      with acceptable toxicity.

PMID- 11535984
TI  - Radiotherapy in epithelial ovarian cancer: state of the art.
AB  - Modern advances in surgery, chemotherapy (CT) and radiotherapy (RT) have not,
      unfortunately, impacted the overall survival for patients with ovarian cancer
      (OC). Despite its long history in the treatment of OC and its proven curative
      role in patients with microscopic or minimal residual disease, the proper role of
      RT in the management of OC is controversial and not clearly established.
      Similarly, the potential roles of RT in the consolidative treatment and as
      salvage therapy following CT failure remain controversial. In the present review
      current issues in the radiotherapeutic management are discussed along with
      possible future clinical research directions.

PMID- 11535985
TI  - Surgery of germ cell tumours of the ovary.
AB  - The surgical management of germ cell tumours of the ovary is based on the premise
      of preserving fertility. Ovarian germ cell tumours occur in young women in whom
      fertility preservation is of great concern. Overwhelmingly ovarian germ cell
      tumours are benign, the most common form of which is the benign cystic teratoma
      (dermoid cyst). Cystectomies with preservation of the ovarian remnant should be
      the routine surgical treatment of benign cystic teratomas. Management of ovarian
      germ cell malignancies also focuses on preservation of fertility. These tumours,
      with the exception of dysgerminoma are overwhelmingly unilateral. All are
      exquisitely sensitive to cytotoxic chemotherapy and fertility has been preserved
      and successful conception has occurred even in women with advanced stage disease
      following surgery and chemotherapy. Cytoreductive surgery plays a role in the
      treatment of non-dysgerminomatous ovarian germ cell malignancies, but is not
      necessary for the management of ovarian dysgerminomas as the latter are
      exquisitely sensitive to chemotherapy. Second-look surgery is no longer routinely
      recommended in the management of these disorders due to the low incidence of
      positivity when patients have been treated with modern combination chemotherapy.
      The role of surgery in the management of recurrent disease has yet to be
      established due to the low incidence of persistent disease following modern
      combination chemotherapy.

PMID- 11535986
TI  - Management of ovarian germ cell tumours.
AB  - Malignant ovarian germ cell tumours are rare but they occur in women with a mean
      age of 19 years. It is important that these young patients are not subjected to
      radical surgery. In most of these patients, they can be cured with either surgery
      alone and careful surveillance with a combination of clinical examination,
      computer tomography scanning and serial serum tumour markers. Almost all of those
      with metastatic disease can be cured with cisplatin-based chemotherapy. A relapse
      is rare and most of these young patients will recover menstruation within two to
      six months of completing their chemotherapy and provided they have not had
      radical surgery, most of these patients should be able to complete their families
      normally.

PMID- 11535988
TI  - The role of bone marrow transplantation in acute promyelocytic leukemia.
AB  - Acute promyelocytic leukemia (APL) is characterized by a specific gene
      rearrangement and the generation of the PML-RARalpha fusion transcript which
      results from a translocation between chromosomes 15 and 17. Targeted therapy with
      all-trans retinoic acid (ATRA) and anthracycline-based chemotherapy results in an
      apparent cure in 70-80% of patients. Both allogeneic (ALLO) and autologous (AUTO)
      hematopoietic stem cell transplantation (HSCT) are effective in acute myeloid
      leukemia (AML), but their role in APL is not clear given the excellent outcome
      with ATRA and chemotherapy. Several retrospective studies have analyzed the
      outcome of patients undergoing AUTO or ALLO-HSCT in first (CR1) or second (CR2)
      complete remission. Most of these studies have shown significant transplant
      related mortality (TRM) with ALLO-HSCT, but a reduction in relapse rate compared
      with AUTO-HSCT. The high TRM with ALLO-HSCT and the excellent outcome with ATRA
      and chemotherapy do not justify recommending this procedure for the majority of
      patients in CR1. The role of AUTO-HSCT in CR1 also is unclear. A small subset of
      patients at high risk of relapse, possibly identifiable by a high white blood
      cell count at presentation may benefit from HSCT. Most patients with relapsed
      disease achieve CR2 with ATRA, arsenic trioxide, or combination therapy. However,
      it is not known if these responses are sustained or if consolidation with HSCT
      has a place in this setting. The outcome of AUTO-HSCT in CR2 using stem cells
      that are negative for PML-RARalpha is excellent. It is unclear whether ALLO-HSCT
      from an HLA-identical sibling is superior to AUTO-HSCT with PML-RARalpha-negative
      cells in CR2 since the former would be associated with graft-versus-leukemia
      effects and the latter with lower TRM. Alternatively, arsenic trioxide or re
      treatment with ATRA, followed by intensive chemotherapy may also be effective. A
      randomized prospective clinical trial, or a retrospective analysis of the
      available data would be useful in answering this critical question.

PMID- 11535987
TI  - Circulating tumour markers in ovarian tumours.
AB  - Many circulating tumour markers are in clinical or experimental use for the
      management of ovarian tumours. The only marker to have an established role in the
      diagnosis, monitoring treatment, and detection of relapse of epithelial ovarian
      cancer (OC) is cancer antigen-125 (CA-125). The place of markers in predicting
      prognosis, in follow-up, and in screening for OC, is less well defined. This
      review concentrates on epithelial cancer of the ovary, and on CA-125, the most
      commonly-used OC marker. Other markers in epithelial OC are also discussed, as
      well as markers used in the management of germ cell tumours of the ovary, mixed
      Mullerian tumours, and stromal ovarian tumours.

PMID- 11535989
TI  - Cutaneous manifestations of maternal engraftment in patients with severe combined
      immunodeficiency: a clinicopathologic study.
AB  - SCID is a heterogeneous group of disorders characterized by defective T cell and
      B cell function. Eczematous and morbilliform eruptions are common, and graft
      versus-host disease (GVHD) due to maternal engraftment has been documented. We
      sought to better characterize SCID-related cutaneous disease observed prior to
      BMT and to compare the eruption to conventional GVHD. Medical records of 51
      patients with SCID treated between 1982 and 1999 were reviewed. Ten of 51 (20%)
      had rash and evidence of maternal engraftment prior to BMT (study group). Eleven
      of 51 (22%) had no rash or evidence of engraftment pre-BMT but developed GVHD
      following transplant (control group). Skin biopsies were available for review for
      8/10 of the study group and for 8/11 of the control group. Cutaneous findings
      consisted of a scaling, erythematous maculopapular eruption spread widely over
      the trunk and extremities, with near-erythroderma in some patients.
      Microscopically, biopsies from the study group differed significantly from
      controls. Key differences included parakeratosis (P < or = 0.01), psoriasiform
      hyperplasia (P < or = 0.04) and spongiosis (P < or = 0.04). The dermatopathologic
      findings of transplacental GVHD differ from the pattern of post-transplant GVHD.
      A 'psoriasiform-lichenoid-spongiotic' pattern with necrotic keratinocytes should
      trigger consideration of SCID and maternal engraftment in the dermatopathologic
      evaluation of eruptions of infancy.

PMID- 11535990
TI  - Multiple cycles of dose-intensive chemotherapy with repeated stem cell support as
      induction treatment in metastatic breast cancer: a feasibility study.
AB  - The purpose of this trial was to study feasibility and tolerance of a dose
      intensive multicyclic alternating induction chemotherapy with repeated stem cell
      support in a series of 43 metastatic breast cancer patients. Anthracycline-naive
      patients (n = 21) received cyclophosphamide 2.5 g/m(2) plus doxorubicin 80
      mg/m(2) alternating every 14 days with paclitaxel 200-350 mg/m(2) plus cisplatin
      120 mg/m(2). Patients who had previously received anthracyclines (n = 22)
      received cisplatin 120 mg/m(2) plus etoposide 600 mg/m(2) alternating with
      paclitaxel 200-350 mg/m(2) plus ifosfamide 8 g/m(2). Peripheral blood stem cells
      were infused after every course except the first, with a median CD34(+) dose of
      2.1 x 10(6)/kg per cycle. Positive selection of CD34(+) cells was performed in
      good mobilizers. The median number of cycles administered was six (4-8), and the
      time interval between them was 17 days. Median summation dose intensities (SDI)
      actually administered for the CA-TP and PE-TI protocol were 4.95 and 4.69,
      respectively (87% of scheduled SDI). There were 15 complete (35%) and 21 partial
      responses (49%), for an overall response rate of 84% (95% CI, 73%-95%). Infection
      or neutropenic fever occurred in 50% of the cycles. There was one treatment
      related death. After a median follow-up of 26 months, the median event-free
      survival was 12 months (95% CI: 10-14) and overall survival was 31 months. These
      high dose-intensity induction treatments seem to be feasible with sequential stem
      cell support.

PMID- 11535992
TI  - Immune reconstitution and production of intracellular cytokines in T lymphocyte
      populations following autologous peripheral blood stem cell transplantation.
AB  - For the better understanding of engraftment properties after autologous
      peripheral blood stem cell transplantation (PBSCT), hematopoietic recovery,
      immune reconstitution and functional capacity of cytokine production in different
      lymphocyte populations were examined. In a prospective study, we examined 24
      patients suffering from different malignancies after autologous PBSCT. The
      examination intervals were 1, 3, 6 and 12 months after PBSCT. T cells, B cells
      and NK cells were analyzed using flow cytometry. The expression and kinetics of
      cytokines in T lymphocytes were evaluated in 10 patients by intracellular
      staining of cytokines after PMA/ionomycin stimulation. We observed rapid
      hematopoietic engraftment proceeding to stable long-term reconstitution. For
      CD3(+) lymphocytes, a consistent reconstitution associated with an increase in
      CD3(+)CD8(+) cytotoxic T cells was observed, whereas the CD3(+)CD4(+)
      helper/inducer T cells remained low (< 200/microl). Impaired B lymphopoiesis with
      severe depression (<1%) was detected 1 month after PBSCT but recovered thereafter
      (12.8% after 3 months). The percentages of cytokine-producing T cells and the
      mean fluorescence intensity (MFI) shifts suggested an insufficient capacity for
      producing IFNgamma, in particular for CD3(+)CD4(+) T cells, compared to healthy
      volunteers early after PBSCT. Rapid hematopoietic recovery and partly impaired
      immune reconstitution, especially regarding the regeneration of B lymphocytes and
      T helper cells, was observed. The CD4(+) subpopulation remained low throughout
      the period of examination, whereas the B cells showed a delayed recovery after 3
      months. Cytokine production proved to be sufficient after in vitro stimulation in
      T cell populations with the exception of IFNgamma synthesis.

PMID- 11535991
TI  - Immune reconstitution following allogeneic stem cell transplantation in
      recipients conditioned by low intensity vs myeloablative regimen.
AB  - We have investigated the immune status of patients with hematologic malignancies
      treated with a low intensity conditioning in preparation for allogeneic stem cell
      transplantation. Conditioning consisted of fludarabine, anti-T lymphocyte
      globulin and low-dose busulfan, followed by infusion of allogeneic blood stem
      cells. This protocol resulted in rapid engraftment and complete replacement of
      host with donor hematopoietic cells. Immunological parameters of these patients
      were compared to those patients who were conditioned by an aggressive
      myeloablative regimen. Distribution of cell surface markers of lymphocyte subsets
      from both groups of patients was similar, but different from that of normal
      control cells. Reduced intensity or non-myeloablative conditioning prior to
      allogeneic stem cell transplantation (NST), hardly lowered the normal T cell
      dependent mitogenic response even during the early period following transplant,
      while the myeloablative treatments resulted in a suppressed mitogenic reaction
      and in slow immune recovery. Reactivity of non-MHC restricted cytotoxic T cells
      was also at a normal level in patients who were treated with NST. We conclude
      that stem cell engraftment following reduced conditioning may result in early
      reconstitution of immune responses assessed in vitro. We hypothesize that
      clinical application of NST may lead to faster development of effective immune
      responses against residual host-type malignant and abnormal non-malignant
      hematopoietic cells, although the role of fludarabine on post-transplant
      infections remains to be investigated in a larger cohort of patients.

PMID- 11535993
TI  - Glycosylated vs non-glycosylated granulocyte colony-stimulating factor (G-CSF)-
      results of a prospective randomised monocentre study.
AB  - The discovery of the haematopoietic growth factor granulocyte colony-stimulating
      factor (G-CSF) has reduced infection-related morbidity in cancer patients by
      alleviating post-chemotherapy neutropenia. Two formulations of recombinant human
      (rh) G-CSF, one glycosylated and one non-glycosylated, are available. The
      glycosylated form, lenograstim, possesses at least 25% greater bioactivity in
      vitro. Some comparative studies into the preparation's potential to mobilise
      haematopoietic stem cells suggest a similar advantage. In the light of the great
      clinical importance of G-CSF, we have performed the first prospective,
      randomised, crossover study on children with chemotherapy-induced neutropenia. G
      CSF (250 microg/m(2)) was started 1 day after the chemotherapy block, and was
      administered until a WBC >1500/microl was achieved on 3 successive days. Thirty
      three G-CSF cycles from 11 patients (16 lenograstim, 17 filgrastim) were studied.
      They were investigated for duration of very severe (WBC <500/microl, 9 vs 9.5
      days, lenograstim vs filgrastim, median) and severe leukopenia (WBC <1000/microl,
      11 vs 11 days), infections (CRP >5 mg/dl, 5 vs 5.5 days), infection-related
      hospital stay (11 vs 9 days) and antibiotic treatment (9 vs 9 days). Statistical
      evaluation by paired analysis could not detect any difference between treatment
      groups; the median difference for all end-points was zero. In summary, at least
      at 250 microg/m(2), in terms of their clinical effect on neutropenia, the two G
      CSF preparations appear to have identical activity.

PMID- 11535994
TI  - Valacyclovir for the prevention of cytomegalovirus infection after allogeneic
      stem cell transplantation: a single institution retrospective cohort analysis.
AB  - A retrospective single center study was performed to evaluate the safety and
      efficacy of valacyclovir for prevention of cytomegalovirus (CMV) infection
      (reactivation) after allogeneic stem cell transplantation (SCT). We compared a
      group of 31 patients at risk for CMV reactivation (donor, recipient or both
      seropositive for CMV) who received valacyclovir at an oral dose of 1 g three
      times a day for CMV prophylaxis with a matched cohort of 31 patients who did not
      receive the drug or any other form of CMV prophylaxis. Valacyclovir was used as
      primary prophylaxis in 12 patients and as secondary prophylaxis (after a prior
      CMV reactivation was effectively treated with either ganciclovir or foscarnet and
      without CMV antigenemia at the start of valacyclovir) in the remaining 19
      patients. The two treatment groups were well matched for the donor-recipient CMV
      serological status and other pre-transplant characteristics. CMV reactivation was
      detected by blood antigenemia testing using a commercially available
      immunofluorescence assay for CMV lower matrix protein pp65 in circulating
      leukocytes. For primary prophylaxis, 3/12 patients who received valacyclovir
      reactivated CMV compared to 24/31 patients in the control group (P < 0.001). For
      secondary prophylaxis, 5/19 valacyclovir patients reactivated compared to 16/24
      control patients (P < 0.05). Valacyclovir was well tolerated except for
      infrequent and mild gastrointestinal side-effects. There was no difference in the
      incidence of CMV disease in the two groups. Prophylaxis with valacyclovir appears
      to be safe and efficacious in preventing both primary and secondary CMV
      reactivation in at-risk patients after allogeneic SCT. Larger prospective
      randomized studies will be required to confirm these observations.

PMID- 11535995
TI  - Respiratory syncytial virus infections in autologous blood and marrow transplant
      recipients with breast cancer: combination therapy with aerosolized ribavirin and
      parenteral immunoglobulins.
AB  - Scant data are available concerning the impact and response to therapy of
      respiratory syncytial virus (RSV) infections in patients undergoing autologous
      blood and marrow transplantation (BMT) for breast cancer. During eight winter
      seasons from 1992-1993 to 1999-2000, nine (4%) of 249 such patients were
      hospitalized with RSV infections. Six patients, including all five patients who
      were early post transplant in the pre-engraftment period, developed pneumonia and
      were treated with a combination of aerosolized ribavirin and IVIG. Among five
      patients with pneumonia in whom therapy was initiated prior to respiratory
      failure, one (20%) died. The sixth patient, in whom therapy was initiated after
      respiratory failure developed, also died. In total, two (1%) patients, both of
      whom were in the pre-engraftment period, died of progressive pneumonia. In
      conclusion, RSV is a significant cause of life-threatening pneumonia in
      autologous BMT recipients with breast cancer during the early post-transplant
      period, and accounted for a substantial portion of the overall transplant-related
      mortality, which in recent years has been minimal.

PMID- 11535996
TI  - Serum cardiac troponin I levels and ECG/Echo monitoring in breast cancer patients
      undergoing high-dose (7 g/m(2)) cyclophosphamide.
AB  - High-dose cyclophosphamide (HD-CTX) is largely employed in high-dose chemotherapy
      (HD-CHT) protocols. HD-CTX dose-limiting toxicity expresses itself as cardiac
      toxicity which is fatal in a minority of patients. The pathophysiology of HD-CTX
      associated cardiotoxicity is still poorly understood. Autopsy studies in patients
      who died from acute HD-CTX-induced cardiac toxicity revealed hemorrhagic
      myocardial cell death and interstitial edema. Recently troponins, in particular
      troponin I (cTnI), have been found to represent a uniquely sensitive and specific
      marker of myocyte membrane integrity and therefore to increase in response to
      minimal myocardial cell damage in different settings, including doxorubicin
      induced cardiotoxicity. We performed a multiparametric cardiologic monitoring in
      16 consecutive breast cancer patients undergoing HD-CTX by means of serial ECG
      registrations and cardiac enzymes (CPK, CPK-MB and cTnI) determinations plus
      echocardiography in order to clarify acute cardiac events following HD-CTX
      administration. Neither overt cardiac toxicity nor cardiac enzymes elevation were
      recorded. Serial ECGs revealed in six cases little and reversible reduction of
      QRS voltage and/or ST abnormalities. Echo monitoring showed in four cases mild
      and transient increase of LV diastolic/systolic diameter/volume without decrease
      of FS% or EF% below normal values: in two of them abnormalities of diastolic
      function (E/A mitral doppler ratio) were also recorded. We conclude that our
      protocol of HD-CTX administration does not cause myocardial cell damage as
      analyzed by serum cTnI levels, thus suggesting that myocyte membrane injury may
      not be the first direct mechanism of HD-CTX cardiotoxicity. ECG (ie QRS voltages
      ) and Echo (ie E/A ratio) monitoring leads us to hypothesize that slight
      interstitial edema with reduction of LV diastolic compliance may be initial signs
      of cardiac dysfunction in this clinical setting.

PMID- 11535997
TI  - Serious cardiac complications during bone marrow transplantation at the
      University of Minnesota, 1977-1997.
AB  - Cardiac complications may result from high-dose chemotherapy or irradiation
      administered during the conditioning phase of bone marrow and blood stem cell
      transplantation (BMT). To assess the frequency of clinically serious cardiac
      toxicity related to the acute phase of BMT, we retrospectively examined life
      threatening or fatal cardiotoxicity identified using the complications records of
      our transplant center clinical database. All serious cardiac toxicity events
      within 100 days of BMT except those attributable to septic shock, pneumonitis or
      multi-organ failure were reviewed. Of 2821 BMT patients at the University of
      Minnesota between 1977 and 1997, 26 were identified as having suffered major or
      fatal (n = 13) cardiotoxicity (0.9%, 19 adults and seven children). Rapidly
      progressive heart failure resulted in death of 11 patients, one patient had fatal
      pericardial tamponade, and one had an acute ventricular fibrillation arrest. The
      remaining 13 patients (50%) had life-threatening cardiotoxicity including four
      patients with pericardial tamponade and nine patients with cardiac arrhythmias.
      Overall, we observed that acute, major cardiotoxic events attributable to BMT are
      uncommon, occurring with a frequency of <1%. These data suggest that with
      appropriate pre-transplant clinical evaluation, high-dose cyclophosphamide and
      irradiation in the BMT preparative phase does not result in frequent, clinically
      relevant short-term cardiac toxicity.

PMID- 11535998
TI  - Does gastroenterology consultation change management of patients receiving
      hematopoietic stem cell transplantation?
AB  - Gastrointestinal complications following hematopoietic stem cell transplantations
      (HSCTs) are common, but it is unknown how often gastroenterology consultation
      (GEC) early post BMT leads to specific changes in patient management. We aimed to
      determine the reason(s) for GEC, the diagnoses found through GEC, whether the
      advice or intervention led to change(s) in management and if intervention led to
      any adverse outcome within the first 100 days post HSCT. We undertook a
      retrospective review of all patients at least 18 years old (n = 197) who
      underwent HSCT between November 1990 and April 1998. Of these, 79 patients had 92
      consultations for a total of 163 separate GE problems within the first 100 days
      post HSCT. Data were obtained through chart review. It was determined whether the
      intervention or advice given by the consultant led to actual changes in patient
      management or outcome. We found that the characteristics more likely to be
      associated with GEC included female patient vs male (P = 0.03), allogeneic vs
      autologous transplants (P < 0.001), hematologic vs solid malignancies (P =
      0.006), and leukemias vs lymphomas (P = 0.013). Overall, a definitive diagnosis
      for an identified complaint was made in 71% (range 25-87%). A change in
      management was effected in 54% of cases (range 0-59%). Endoscopy led to
      perforation and subsequent death in two patients (1.8%). Gastrointestinal disease
      was a direct cause of death in 2.5% of all patients. In conclusion, a definite
      diagnosis was reached in 71% of gastrointestinal problems and management was
      effected in 54% of cases. Since endoscopy was associated with a mortality of
      1.8%, minimizing its use for the cases in which no impact is made, should be
      considered.

PMID- 11536000
TI  - Successful treatment of POEMS syndrome with autologous hematopoietic progenitor
      cell transplantation.
AB  - POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal
      gammopathy, and skin changes) is a plasma cell dyscrasia that differs
      substantially from classic multiple myeloma. It is often associated with
      disabling polyneuropathy in younger patients. Current therapeutic approaches are
      frequently inadequate and leave many patients wheelchair-bound with significant
      deterioration in quality and length of life. We present the case of a young man
      with progressive disease despite conventional therapeutic approaches. We describe
      a novel approach to treatment with a bone-seeking radiopharmaceutical, samarium
      153 ethylene diamine tetramethylene phosphonate ((153)Sm-EDTMP), followed by
      myeloablative chemotherapy with autologous hematopoietic progenitor cell
      reconstitution. This approach resulted in regression of the organomegaly and skin
      changes and in neurologic improvement both clinically and electrophysiologically.
      The patient progressed from being wheelchair-bound to independent ambulation. An
      aggressive approach should be considered in patients with POEMS syndrome in whom
      standard therapeutic measures fail.

PMID- 11535999
TI  - A phase II trial evaluating the safety and effectiveness of the AastromReplicell
      system for augmentation of low-dose blood stem cell transplantation.
AB  - To reduce the number of apheresis procedures and maintain the usual rate of
      hematopoietic recovery in patients treated with high-dose chemotherapy, we
      studied the effect of adding a small volume of ex vivo expanded bone marrow to
      low doses of CD34(+) blood stem cells. Thirty-four patients with breast cancer
      received G-CSF (10 microg/kg/day) priming followed by a limited volume (50-100
      ml) bone marrow aspiration and standard 10-liter aphereses. Marrow was expanded
      ex vivo using the AastromReplicell system and infused along with low doses of
      blood-derived CD34(+) cells, collected in one apheresis. Thirty-one evaluable
      patients received a median CD34(+) blood stem cell dose of 0.7 x 10(6)/kg (range,
      0.2-2.5) and 4.7 x 10(7) nucleated cells/kg (range, 1.98-8.7) of ex vivo expanded
      marrow. All patients recovered with normal blood counts and engrafted 500
      neutrophils/microl and 20 000 platelets/microl in a median of 10 and 13 days,
      respectively. Multivariate analysis revealed that, in addition to CD34(+) lineage
      negative cell quantity, the quantity of stromal progenitors contained in the ex
      vivo expanded product correlated with engraftment outcome (r = 0.551, P = 0.004).
      Our results indicate that ex vivo expanded bone marrow is capable of facilitating
      engraftment when combined with low doses of mobilized blood derived CD34(+)
      cells.

PMID- 11536001
TI  - Life-threatening capillary leak syndrome after G-CSF mobilization and collection
      of peripheral blood progenitor cells for allogeneic transplantation.
AB  - We report a case of capillary leak syndrome in a 37-year-old female PBPC donor
      who received G-CSF 900 microg/day for 4 days and underwent leukapheresis. This
      lady had remained well and stable despite marked leukocytosis during G-CSF
      treatment, but developed hypotension during leukapheresis, quickly followed by
      hypoxemia, ascites, pericardial and pleural effusion, shock, edema, neurologic
      changes and hepatocellular injury. Upon G-CSF withdrawal, dopamine and
      crystalloid infusion, methylprednisolone treatment and suspension of apheresis,
      the clinical situation fully reversed. We hypothesize that leukapheresis, in the
      presence of marked leukocytosis and high doses of G-CSF, may have triggered
      neutrophil activation and the release of inflammatory mediators, resulting in
      tissue damage and systemic manifestations of increased capillary permeability.

PMID- 11536002
TI  - T cell-depleted nonmyeloablative stem cell transplantation: what is the optimum
      balance between the intensity of host conditioning and the degree of T cell
      depletion of the graft?